PMID- 24432290
TI  - At the end of summer.

PMID- 24432288
TI  - Primary cerebral echinococcosis presenting as long-standing generalized weakness.
AB  - Echinococcosis is an infectious disease that can remain dormant for years. The
      most common sites of infection are liver and lungs. Primary cerebral disease is
      very rare. Here we report on an unusual case of echinococcosis, where the only
      identifiable lesion was a slowly growing intracranial hydatid cyst. No lesions on
      the liver identified. The patient is a United States immigrant from rural South
      India with a chief complaint of progressive weakness and aphasia. Further
      analysis revealed an interesting association between the clinical, anatomical and
      hematological findings over time. We conclude that hydatid cyst disease should be
      considered in patients from endemic areas with long-standing neurological
      symptoms. 

PMID- 24432291
TI  - The role of rotavirus associated with pediatric gastroenteritis in a general
      hospital in Lagos, Nigeria.
AB  - INTRODUCTION: Bacterial, viral and parasitic agents have been implicated and
      confirmed as causative agents of gastroenteritis in children with ages below 5
      years old. The major role of rotavirus as causative agent is not widely
      recognized within the public health community, particularly in developing
      countries. This study examined the role of rotavirus as a causative agent of
      childhood gastroenteritis in infants and young children below 5 years of age in a
      General Hospital in Lagos, Nigeria. METHODS: Parents and caregivers of children
      admitted to the hospital were interviewed using a structured questionnaire. Viral
      RNA was extracted from the stool samples collected and analyzed using RT-PCR for
      genotyping and agarose gel electrophoresis for identification of rotavirus
      electrophoretypes. RESULTS: Out of the 71 samples analyzed, 16 (22.5%) were
      positive for rotavirus. A total of 12 (75%) males and 4 (25%) females were
      positive for rotavirus gastroenteritis with most cases (7, 43.8%) distributed to
      the 13-24 months age group, followed closely by the 1-6 months age group, with 6
      cases, 37.5%. Rotavirus G2 genotype was the most prevalent strain in the hospital
      (10 patients, 62.5%) followed by G1 (6 patients, 37.5%). These were the only
      rotavirus genotypes detected in the hospital.

PMID- 24432292
TI  - Nine-year follow-up of HIV-infected Romanian children and adolescents receiving
      lopinavir/ritonavir-containing highly active antiretroviral therapy.
AB  - INTRODUCTION: Many Romanian children were infected nosocomially with human
      immunodeficiency virus (HIV) in the late 1980s. The Romanian-American Children's
      Center of Excellence in Constanta continues to follow approximately 450 of these
      patients. In 2001, 414 of these patients were initiated on triple therapy
      including lopinavir/ritonavir. Data from this cohort treated through August 2006
      were published in April 2007 demonstrating that the treatment was well tolerated,
      with 337 children (81%) remaining on therapy after a median duration of >4 years.
      The current article describes the results of continued analysis of this cohort
      through end 2010. The objective of the study was to determine the long-term
      clinical outcomes of children and adolescents commenced on antiretroviral therapy
      (ART) including lopinavir/ritonavir. METHODS: Data were extracted retrospectively
      from the charts of the 336 patients remaining on lopinavir/ritonavir in August
      2006. The following outcomes were analyzed: mortality, current patient status,
      viral load (VL), CD4 counts and reasons for discontinuation of
      lopinavir/ritonavir. RESULTS: The median age at initiation of lopinavir/ritonavir
      was 14.0 years (range 5.4 to 20.0 years). The median time on lopinavir/ritonavir
      treatment was 7.5 years (interquartile range 5.7 to 8.6 years). Overall mortality
      was 13.5%. Of the original 414 patients started on lopinavir/ritonavir in 2001,
      199 (48.1%) remained on this therapy at the end of 2010 and of these 63.8% had
      undetectable viral load. CONCLUSION: Despite initial suboptimal ART, a
      significant proportion of patients subsequently treated with a
      lopinavir/ritonavir based regimen remained on this therapy for up to nine years.

PMID- 24432293
TI  - Permanent pacemaker-associated actinomycetemcomitans endocarditis: A case report.
AB  - Aggregatibacter actinomycetemcomitans is a Gram-negative bacillus, member of the
      HACEK group of bacteria, and it is a very rare cause of endocarditis. It is also
      an extremely rare cause of device-associated infection of the heart. We describe
      the case of a 25 year-old man who presented with pacemaker-associated
      endocarditis due to Aggregatibacter actinomycetemcomitans and also discuss the
      implications and treatment of this organism. 

PMID- 24432294
TI  - Hepatitis C in the interferon-free era.

PMID- 24432295
TI  - Antibiotic prophylaxis in retrograde ureteroscopy: what strategy should we adopt?
AB  - BACKGROUND: Retrograde ureteroscopy as a minimally invasive treatment of ureteral
      calculi can be complicated by the occurrence of urinary tract infections. Fever
      is considered the main indicator of such postoperative complications and we aimed
      to study its incidence in patients with and without preoperative antibiotic
      prophylaxis. METHODS: We included all patients who underwent retrograde
      ureteroscopy for ureteric stones in the Iasi and Tg Mures Urology Clinics from
      2009 to 2012. Data were statistically analyzed using the EpiInfo 7 software.
      Indicative of a statistically significant difference was a p value <0.05.
      RESULTS: We recorded fever in a total of 108 cases, accounting for 22.83% of all
      subjects in the study. Group 1 included patients who received antibiotic
      prophylaxis; 48 of 147 (32.65%) were febrile, compared with Group 2 (no
      antibiotic prophylaxis), where we recorded febrile syndrome in 60 (18.40%) cases,
      p=0.0009. Comparing the two groups based on calculus size, for stones with
      diameters of 0.6-0.8 cm 38.71% of patients were febrile in Group 1, compared with
      10.88% in Group 2 (p=0.0008). Secondary ureterohydronephrosis did not
      statistically influence the frequency of fever in any of the studied groups.
      CONCLUSION: Less than half of all febrile patients had positive urine cultures,
      which may point to other causes, such as noninfectious factors (aseptic kidney
      inflammation). This study did not prove the efficiency of preoperative antibiotic
      prophylaxis; however, based on the clinical experience of the past 120 years,
      infectious complications are known to be associated with urological maneuvers and
      prophylaxis could be indicated.

PMID- 24432296
TI  - Association between inbreeding coefficient and susceptibility to HIV-1 infection,
      a case-control study.
AB  - INTRODUCTION: Consanguinity has been associated with adverse health outcomes. The
      objective of the present study was to assess the association between parental
      consanguinity and risk of infection with human immunodeficiency virus type-1 (HIV
      1). METHODS: Data were collected from 333 HIV-1 infected individuals referred to
      a local health center in Shiraz (southern Iran). A total of 999 healthy
      individuals frequency matched with the cases according to their sex and age were
      also studied, as a control group. RESULTS: Prevalence of parental consanguineous
      marriage was 23.7% and 32.8% among patients and controls, respectively
      (Chi(2)=9.880, df=1, p=0.007). The mean inbreeding coefficient was 0.0110 and
      0.0156 among patients and controls, respectively. The risk of infection with HIV
      1 decreased as a function of inbreeding coefficient (Chi(2)=7.531, p=0.006).
      CONCLUSION: The present finding indicates a negative association between the
      susceptibility of HIV-1 infection and the inbreeding coefficient.

PMID- 24432297
TI  - Treatment of periodontal disease with dental curing light - could it be that
      simple?

PMID- 24432298
TI  - Computational fluid dynamics models and congenital heart diseases.
AB  - Mathematical modeling is a powerful tool to investigate hemodynamics of the
      circulatory system. With improving imaging techniques and detailed clinical
      investigations, it is now possible to construct patient-specific models of
      reconstructive surgeries for the treatment of congenital heart diseases. These
      models can help clinicians to better understand the hemodynamic behavior of
      different surgical options for a treated patient. This review outlines recent
      advances in mathematical modeling in congenital heart diseases, the discoveries
      and limitations these models present, and future directions that are on the
      horizon. 

PMID- 24432299
TI  - An Application of Graphical Approach to Construct Multiple Testing Procedures in
      a Hypothetical Phase III Design.
AB  - Many multiple testing procedures (MTP) have been developed in recent years. Among
      these new procedures, the graphical approach is flexible and easy to communicate
      with non-statisticians. A hypothetical Phase III clinical trial design is
      introduced in this manuscript to demonstrate how graphical approach can be
      applied in clinical product development. In this design, an active comparator is
      used. It is thought that this test drug under development could potentially be
      superior to this comparator. For comparison of efficacy, the primary endpoint is
      well established and widely accepted by regulatory agencies. However, an
      important secondary endpoint based on Phase II findings looks very promising. The
      target dose may have a good opportunity to deliver superiority to the comparator.
      Furthermore, a lower dose is included in case the target dose may demonstrate
      potential safety concerns. This Phase III study is designed as a non-inferiority
      trial with two doses, and two endpoints. This manuscript will illustrate how
      graphical approach is applied to this design in handling multiple testing issues.

PMID- 24432300
TI  - Functional role of microvesicles in gastrointestinal malignancies.
AB  - Microvesicles (MVs) are derived from the plasma membrane and are released into
      the intracellular space by outward budding and fission of the plasma membrane of
      cells. Various studies have shown high regulation of microvesicles shedding from
      cells widespread throughout the body, often involving cancerous cells. MVs are
      originated from the endosomal membrane compartment, and after fusion with the
      plasma membrane, they are shed from the cell surface of activated cells.
      Therefore, microvesicles may be secreted by activated malignant and normal cells
      and play a role in cellular communication during cancer development.
      Microvesicles are found in many biological fluids in the body and have been
      demonstrated to receive their functionality from the parent cell from which they
      are derived. MVs facilitate the transfer of proteins and other molecules, thereby
      allowing for interaction with cells and tissues far away from the originating
      cell. This functionality has caused researchers to view microvesicles as a
      primary component of tumor progression and development. This commentary
      summarizes recent literature on the properties and biogenesis of microvesicles,
      and their influence on gastrointestinal tumor progression.

PMID- 24432301
TI  - Effect of high fat-diet and obesity on gastrointestinal motility.
AB  - Obesity is highly prevalent worldwide and is associated with significant
      morbidity and mortality. The focus of this review is to delineate the changes in
      gastrointestinal motility observed in obesity. A systematic review of the
      published literature on obesity and gastrointestinal motility was performed.
      Here, we describe the current understanding of the changes in obesity in the
      esophagus, stomach, small intestine and colon. Major findings include supportive
      evidence for increased gastroesophageal reflux disease and esophageal motility
      disorders in obesity, and a rapid gastric emptying time seen in obese
      individuals. The proximal small intestinal transit seems to be increased in
      obesity and this may be secondary to efficient nutrient absorption and subsequent
      lack of nutrient-induced satiety signals conveyed from the small intestine. In
      obesity, there is some evidence for delayed colonic transit as well as a
      reduction in colonic serotonin availability. The molecular mechanisms underlying
      altered motility in obesity could be secondary to reduced cannabinoids or its
      receptor cannabinoid receptor 1 (CB1) expression as well as due to loss of
      neuronal nitric oxide synthase (nNOS) neurons. The interactions of diet and
      obesity and the alteration of microbiota in this setting are just being explored
      and may offer novel insights into the changes of gastrointestinal motility in
      obesity.

PMID- 24432302
TI  - Molecular Nutrition, Nutrigenomics and Health Promotion: A Long Road Ahead.

PMID- 24432303
TI  - T cells expressing chimeric antigen receptors can cause anaphylaxis in humans.
AB  - T cells can be redirected to overcome tolerance to cancer by engineering with
      integrating vectors to express a chimeric antigen receptor (CAR). In preclinical
      models, we have previously demonstrated that transfection of T cells with
      messenger RNA (mRNA) coding for a CAR is an alternative strategy that has
      antitumor efficacy and the potential to evaluate the on-target off-tumor toxicity
      of new CAR targets safely due to transient mRNA CAR expression. Here, we report
      the safety observed in four patients treated with autologous T cells that had
      been electroporated with mRNA coding for a CAR derived from a murine antibody to
      human mesothelin. Due to the transient nature of CAR expression on the T cells,
      subjects in the clinical study were given repeated infusions of the CAR-T cells
      in order to assess their safety. One subject developed anaphylaxis and cardiac
      arrest within minutes of completing the 3rd infusion. Although human anti-mouse
      IgG antibodies have been known to develop with CAR-transduced T cells, they have
      been thought to have no adverse clinical consequences. This is the first
      description of clinical anaphylaxis resulting from CAR-modified T cells, most
      likely through IgE antibodies specific to the CAR. These results indicate that
      the potential immunogenicity of CARs derived from murine antibodies may be a
      safety issue for mRNA CARs, especially when administered using an intermittent
      dosing schedule.

PMID- 24432304
TI  - Chronic lymphocytic leukemia monitoring with a Lamprey idiotope-specific
      antibody.
AB  - For antigen recognition, lampreys use leucine-rich repeats (LRR) instead of
      immunoglobulin V-(D)-J domains to generate variable lymphocyte receptors (VLR) of
      three types, VLRA, VLRB, and VLRC. VLRB-bearing lymphocytes respond to
      immunization with proliferation and differentiation into plasmacytes that secrete
      multivalent VLRB antibodies. Here we immunized lampreys with B cells from
      patients with chronic lymphocytic leukemia (CLL) to generate recombinant
      monoclonal VLRB antibodies, one of which, VLR39, was specific for the donor CLL
      cells. The target epitope of VLR39 was shown to be the complementarity
      determining region 3 (CDR3) of the heavy chain variable region (VH) of the B cell
      receptor. Using this antibody to monitor the CLL donor after chemo-immunotherapy
      induced remission, we detected VLR39(+) B cells in the patient 51 months later,
      before significant increase in lymphocyte count or CD5(+) B cells. This
      indication of reemergence of the leukemic clone was verified by VH sequencing.
      Lamprey antibodies can exhibit exquisite specificity for a protein epitope, a CLL
      signature VH CDR3 sequence in this case, and offer a rapid strategy for
      generating anti-idiotype antibodies for early detection of leukemia recurrence. 

PMID- 24432305
TI  - Regression of metastatic Merkel cell carcinoma following transfer of polyomavirus
      specific T cells and therapies capable of re-inducing HLA class-I.
AB  - Merkel cell carcinoma (MCC) is an aggressive skin cancer that typically requires
      the persistent expression of Merkel cell polyomavirus (MCPyV) oncoproteins that
      can serve as ideal immunotherapeutic targets. Several immune evasion mechanisms
      are active in MCC including down-regulation of HLA class-I expression on tumor
      cells and dysfunctional endogenous MCPyV-specific CD8 T cell responses. To
      overcome these obstacles, we combined local and systemic immune therapies in a 67
      year-old man, who developed metastatic MCPyV-expressing MCC. Intralesional
      IFNbeta-1b or targeted single-dose radiation was administered as a pre
      conditioning strategy to reverse the down-regulation of HLA-I expression noted in
      his tumors and to facilitate the subsequent recognition of tumor cells by T
      cells. This was followed by the adoptive transfer of ex vivo expanded polyclonal,
      polyomavirus-specific T cells as a source of reactive antitumor immunity. The
      combined regimen was well-tolerated and led to persistent up-regulation of HLA-I
      expression in the tumor and a durable complete response in two of three
      metastatic lesions. Relative to historical controls, the patient experienced a
      prolonged period without development of additional distant metastases (535 days
      compared to historic median of 200 days, 95% confidence interval = 154-260 days).
      The transferred CD8(+) T cells preferentially accumulated in the tumor tissue,
      remained detectable and functional for >200 days, persisted with an effector
      phenotype, and exhibited evidence of recent in vivo activation and proliferation.
      The combination of local and systemic immune stimulatory therapies was well
      tolerated and may be a promising approach to overcome immune evasion in virus
      driven cancers. 

PMID- 24432306
TI  - Circulating Cell and Plasma microRNA Profiles Differ between Non-ST-Segment and
      ST-Segment-Elevation Myocardial Infarction.
AB  - BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs)
      in patients with an acute coronary syndrome (ACS) have been determined in both in
      vitro and in vivo studies. Although most circulating miRNAs are located in the
      cellular components of whole blood, little is known about the miRNA profiles of
      whole blood subcomponents, including plasma, platelets and leukocytes in patients
      with myocardial ischemia. METHODS: Thirteen patients with a ST-segment-elevation
      (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were
      identified in the University of Massachusetts Medical Center Emergency Department
      (ED) or cardiac catheterization laboratory between February and June of 2012.
      Whole blood was obtained from arterial blood samples at the time of cardiac
      catheterization and cell-specific miRNA profiling was performed. Expression of
      343 miRNAs was quantified from whole blood, plasma, platelets, and peripheral
      blood mononuclear cells using a high-throughput, quantitative Real-Time
      polymerase-chain reaction system (qRT-PCR). RESULTS: MiRNAs associated with STEMI
      as compared to NSTEMI patients included miR-25-3p, miR-221-3p, and miR-374b-5p.
      MiRNA 30d-5p was associated with plasma, platelets, and leukocytes in both STEMI
      and NSTEMI patients; miRNAs 221-3p and 483-5p were correlated with plasma and
      platelets only in NSTEMI patients. CONCLUSIONS: Cell-specific miRNA profiles
      differed between patients with STEMI and NSTEMI. The miRNA distribution is also
      unique amongst plasma, platelets, and leukocytes in patients with ischemic heart
      disease or ACS. Our findings suggest unique miRNA profiles among the circulating
      subcomponents in patients presenting with myocardial ischemia.

PMID- 24432307
TI  - Beneficial and harmful roles of bacteria from the Clostridium genus.
AB  - Bacteria of the Clostridium genus are often described only as a biological threat
      and a foe of mankind. However, many of them have positive properties and thanks
      to them they may be used in many industry branches (e.g., in solvents and alcohol
      production, in medicine, and also in esthetic cosmetology). During the last 10
      years interest in application of C. botulinum and C. tetani in medicine
      significantly increased. Currently, the structure and biochemical properties of
      neurotoxins produced by these bacterial species, as well as possibilities of
      application of such toxins as botulinum as a therapeutic factor in humans, are
      being intensely researched. The main aim of this article is to demonstrate that
      bacteria from Clostridium spp. are not only pathogens and the enemy of humanity
      but they also have many important beneficial properties which make them usable
      among many chemical, medical, and cosmetic applications. 

PMID- 24432308
TI  - Silver nanoparticles as an alternative strategy against bacterial biofilms.
AB  - Biofilms are complex bacterial communities that resist the action of antibiotics
      and the human immune system. Bacteria within biofilms are the cause of numerous,
      almost impossible to eradicate, persistent infections. Biofilms can form on many
      medical devices and implants, and so have an enormous impact on medicine. Due to
      the lack of effective anti-biofilm antibiotics, novel alternative compounds or
      strategies are urgently required. This review describes some of the latest
      approaches in the field of biofilm treatment. New anti-biofilm technologies
      target different stages in the biofilm formation process. Some act to modify the
      colonized biomaterials to make them resistant to biofilm formation. One
      potentially important candidate treatment uses silver nanoparticles that show
      anti-bacterial and anti-biofilm activity. The biological action of nano-silver is
      complex and seems to involve a number of pathways. However, there have been few
      reports on the anti-biofilm activity of silver nanoparticles and the precise
      mechanism underlying their action remains unresolved. Here, we describe some anti
      biofilm approaches employing AgNPs and consider the challenges and problems that
      need to be addressed in order to make silver nanoparticles a part of an effective
      anti-biofilm strategy. 

PMID- 24432309
TI  - Microscopic findings for the study of biofilms in food environments.
AB  - The capability of bacteria to colonize food processing surfaces and to form
      biofilm has become an emerging concern for food industry. The presence and
      persistence of biofilm on food processing surfaces may pose a risk of food
      spoilage or food poisoning. A better understanding of bacterial adhesion and
      resistance of biofilms is needed to ensure quality and safety of food products.
      This review focuses on microscopic approaches incorporated to explore biofilm
      mode of existence in food processing environments. An application of
      antimicrobial agents for the biofilm control, in particular for bacteria
      connected with food processing environments, is also highlighted. In addition,
      some aspects of biofilm resistance, especially the phenomenon of persister cells,
      are discussed. 

PMID- 24432310
TI  - Limited GADD45alpha expression and function in IL-1beta toxicity towards insulin
      producing cells.
AB  - Growth arrest and DNA damage-inducible (GADD) 45 proteins are regulators of cell
      death and survival. The proinflammatory cytokine IL-1beta strongly increases the
      level of the transcript encoding GADD45alpha in rat insulin-producing INS-1E
      cells. The activation of Gadd45alpha gene is clearly dependent on JNK and NF
      kappaB activation and the synthesis of the secondary mediator nitric oxide (NO).
      Interestingly, the observed twelve-fold increase in the GADD45alpha-coding
      transcript level is not followed by increased expression of GADD45alpha at the
      protein level. An analysis of IL-1beta toxicity in INS-1E cells overexpressing
      GADD45alpha revealed no correlation between the GADD45alpha protein level and the
      sensitivity to IL-1beta toxicity. These findings suggest that the potential
      engagement of GADD45alpha in IL-1beta toxicity towards beta cells is limited to
      the effects induced by the basal expression level of this protein. 

PMID- 24432311
TI  - Metformin reduces NAD(P)H oxidase activity in mouse cultured podocytes through
      purinergic dependent mechanism by increasing extracellular ATP concentration.
AB  - Hyperglycemia affects the functioning numbers of podocytes and leads to a gradual
      decline of renal function. The normalization of glucose level is a principle
      therapeutic goal in diabetic patients and metformin is a popular hypoglycemic
      drug used in type 2 diabetes mellitus. Metformin activates AMP-activated kinase
      (AMPK) and decreases NAD(P)H oxidase activity in podocytes leading to reduction
      of free radical generation. Similar effects are observed after activation of P2
      receptors. Therefore, we investigated whether metformin increases extracellular
      ATP concentration and affects the activities of NAD(P)H oxidase and AMPK through
      P2 receptors. Experiments were performed on cultured mouse podocytes. NAD(P)H
      oxidase activity was measured by chemiluminescence and changes in AMPK activity
      were estimated by immunoblotting against AMPKalpha-Thr(172)-P. Metformin
      increased extracellular ATP concentration by reduction of ecto-ATPase activity,
      decreased NAD(P)H oxidase activity and increased AMPK phosphorylation. A P2
      receptor antagonist, suramin (300 uM), prevented metformin action on NAD(P)H
      oxidase and AMPK phosphorylation. The data suggests a novel mechanism of
      metformin action, at least in podocytes. Metformin, which increases extracellular
      ATP concentration leads to activation of P2 receptors and consequent modulation
      of the podocytes' metabolism through AMPK and NAD(P)H oxidase which, in turn, may
      affect podocyte functioning. 

PMID- 24432312
TI  - Characterization of a possible uptake mechanism of selective antibacterial
      peptides.
AB  - Selective antibacterial peptides containing less than 30 amino acid residues,
      cationic, with amphipathic properties, have been the subject of several studies
      due to their active participation and beneficial effects in strengthening the
      immune system of all living organisms. This manuscript reports the results of a
      comparison between the group of selective antibacterial peptides and another
      group called "cell penetrating peptides". An important number of the selective
      antibacterial peptides are cell penetrating peptides, suggesting that their
      toxicity is related to their uptake mechanism. The verification of this
      observation also includes the adaptation of a method previously published, called
      Polarity index, which reproduces and confirms the action of this new set of
      peptides. The efficiency of this method was verified based on four different
      databases, yielding a high score. The verification was based exclusively on the
      peptides already reported in the databases which have been experimentally
      verified. 

PMID- 24432313
TI  - Microarray Inspector: tissue cross contamination detection tool for microarray
      data.
AB  - Microarray technology changed the landscape of contemporary life sciences by
      providing vast amounts of expression data. Researchers are building up
      repositories of experiment results with various conditions and samples which
      serve the scientific community as a precious resource. Ensuring that the sample
      is of high quality is of utmost importance to this effort. The task is
      complicated by the fact that in many cases datasets lack information concerning
      pre-experimental quality assessment. Transcription profiling of tissue samples
      may be invalidated by an error caused by heterogeneity of the material. The risk
      of tissue cross contamination is especially high in oncological studies, where it
      is often difficult to extract the sample. Therefore, there is a need of
      developing a method detecting tissue contamination in a post-experimental phase.
      We propose Microarray Inspector: customizable, user-friendly software that
      enables easy detection of samples containing mixed tissue types. The advantage of
      the tool is that it uses raw expression data files and analyses each array
      independently. In addition, the system allows the user to adjust the criteria of
      the analysis to conform to individual needs and research requirements. The final
      output of the program contains comfortable to read reports about tissue
      contamination assessment with detailed information about the test parameters and
      results. Microarray Inspector provides a list of contaminant biomarkers needed in
      the analysis of adipose tissue contamination. Using real data (datasets from
      public repositories) and our tool, we confirmed high specificity of the software
      in detecting contamination. The results indicated the presence of adipose tissue
      admixture in a range from approximately 4% to 13% in several tested surgical
      samples. 

PMID- 24432314
TI  - Comparing the rate of growth and metabolic efficiency of yeast experiencing
      environmental stress or genetic damage.
AB  - Physical stresses, toxic substances, and mutations can cause marked decline in
      the rate of growth (RG). We report that the efficiency of growth (EG), i.e.
      converting glucose into biomass, responds less profoundly. It remains nearly
      unaffected for some physical and chemical stresses, but decreases substantially
      for others, specifically those affecting membrane integrity or ion homeostasis.
      Mutations (gene deletions) can heavily reduce RG, but much less EG. Moreover,
      there is no apparent relation between the function of deleted gene and EG.
      Generally, assays of EG appear as more laborious, less precise, and less
      informative than those of RG. 

PMID- 24432315
TI  - The citric acid-modified, enzyme-resistant dextrin from potato starch as a
      potential prebiotic.
AB  - In the present study, enzyme-resistant dextrin, prepared by heating of potato
      starch in the presence of hydrochloric (0.1% dsb) and citric (0.1% dsb) acid at
      130oC for 3 h (CA-dextrin), was tested as a source of carbon for probiotic
      lactobacilli and bifidobacteria cultured with intestinal bacteria isolated from
      feces of three healthy 70-year old volunteers. The dynamics of growth of
      bacterial monocultures in broth containing citric acid (CA)-modified dextrin were
      estimated. It was also investigated whether lactobacilli and bifidobacteria
      cultured with intestinal bacteria in the presence of resistant dextrin would be
      able to dominate the intestinal isolates. Prebiotic fermentation of resistant
      dextrin was analyzed using prebiotic index (PI). In co-cultures of intestinal and
      probiotic bacteria, the environment was found to be dominated by the probiotic
      strains of Bifidobacterium and Lactobacillus, which is a beneficial effect. 

PMID- 24432316
TI  - Utilization of 4-n-nonylphenol by Metarhizium sp. isolates.
AB  - Nonylphenol (4-NP) is a xenobiotic classified as an endocrine disrupting compound
      with an ability to interfere with hormonal systems of numerous organisms
      including humans. It is widely distributed not only in aquatic but also in
      terrestrial systems. The aim of this study was to evaluate the ability of
      cosmopolitan fungus Metarhizium (commonly persistent in soil as a facultative
      insect pathogen, controlling populations of arthropods in natural environment) to
      degrade 4-n-nonylphenol. All isolates examined in this work were identified to a
      species rank based on five, independent genetic markers. Among eight Metarhizium
      strains; six of them have been identified as M. robertsii, and two others as M.
      brunneum and M. lepidiotae. All investigated Metarhzium isolates were found to
      eliminate 4-n-NP with significant efficiency (initial xenobiotic concentration 50
      mg L(-1)). The degradation process was very effective and at 24h of incubation 50
      90% of 4-n-NP was eliminated by certain strains, while extended incubation
      resulted in further utilization of this compound. At the end of the experiments
      64-99% of 4-n-NP was removed from the culture medium. Additionally, in all tested
      cultures three major metabolites were detected: 4-hydroxybenzoic acid; 2-(4
      hydroxyphenyl)acetic acid and 4-hydroxyphenylpentanoic acid. The obtained results
      indicate that Metarhizium sp. possesses an ability to degrade NP and can serve as
      a potential candidate for further biodegradation studies. 

PMID- 24432317
TI  - Transforming growth factor beta1 protein and mRNA levels in inflammatory bowel
      diseases: towards solving the contradictions by longitudinal assessment of the
      protein and mRNA amounts.
AB  - Previously published studies on levels of the transforming growth factor-beta1
      (TGF-beta1) protein and mRNA of the corresponding gene in patients suffering from
      inflammatory bowel diseases (IBD) gave varying results, leading to contradictory
      conclusions. To solve the contradictions, we aimed to assess longitudinally TGF
      beta1 protein and mRNA levels at different stages of the disease in children
      suffering from IBD. The study group consisted of 19 pediatric patients with IBD
      at the age between 3.5 and 18.4 years. The control group consisted of 42 children
      aged between 2.0 and 18.0 years. The plasma TGF-beta1 concentration was measured
      with ELISA. mRNA levels of the TGF-beta1 gene isolated from samples of the
      intestinal tissue were assessed by reverse transcription and real-time PCR.
      Levels of TGF-beta1 protein in plasma and corresponding mRNA in intestinal tissue
      were significantly higher in IBD patients than in controls. TGF-beta1 and
      corresponding transcripts were also more abundant in plasma and intestinal
      tissue, respectively, in patients at the active stage of the disease than during
      remission. In every single IBD patient, plasma TGF-beta1 level and mRNA level in
      intestinal tissue was higher at the active stage of the disease than during
      remission. Levels of TGF-beta1 and corresponding mRNA are elevated during the
      active stage of IBD but not during the remission. Longitudinal assessment of this
      cytokine in a single patient may help to monitor the clinical course of IBD. 

PMID- 24432318
TI  - Microflora of the selected water reservoirs in Swietokrzyskie Voivodship.
AB  - One of the important environmental issues is the quality of surface waters in the
      world. Poland belongs to countries with a low quality of the inland waters. The
      sanitary condition of the five water reservoirs of south-east Poland was
      analyzed. Water and sediment samples were incubated on the selective and/or
      differential media. High concentrations of many common and pathogenic microbial
      indicators were shown in those samples. Those reservoirs are used by people,
      especially during summer. Because of the high epidemiological risk, detailed
      analysis of all inland waters should be performed routinely. 

PMID- 24432319
TI  - Comparative study of metal induced phospholipid modifications in the heavy metal
      tolerant filamentous fungus Paecilomyces marquandii and implications for the
      fungal membrane integrity.
AB  - In this work we compared the effect of five heavy metals: Zn, Pb, Cd, Ni and Cu
      on phospholipid composition of the ubiquitous soil fungus Paecilomyces
      marquandii, originating from a strongly metal polluted area and characterized by
      high tolerance to these elements. Cd, Ni and Cu caused an increase in
      phosphatidylcholine (PC). Only Pb decreased PC content, which was accompanied by
      a significant rise in the phosphatidic acids (PA) level, probably due to
      activation of phospholipase D which hydrolyzes PC to PA. This could result in
      membrane fluidity disturbance, and thus affect its integrity. The assessment of
      propidium iodide influx showed strong disturbance of membrane integrity for Cu
      and Pb stressed mycelia, whereas mycelia treated with Ni were impermeable to this
      dye. The results obtained revealed a strong Cu and Pb toxicity involving
      disruption of membrane integrity. Pb action was reflected by lipid composition,
      whereas changes in Cu treated mycelia did not completely elucidate its harmful
      effect on the membrane, which was most probably caused by Cu induced lipid
      peroxidation. Zn did not induce quantitative changes in PC and
      phosphatidylethanolamine (PE) but caused changes in phospholipid lipid
      saturation, which appears to be important for fungus adaptation to the presence
      of metals. The enhanced PC content balanced by higher PC saturation can help in
      the maintenance of proper membrane fluidity and result in alleviating the Cd and
      Ni induced stress. These results will allow to clarify the mechanism of Pb
      toxicity and help to elucidate the cellular basis of fungal membrane adaptation
      to heavy metals. 

PMID- 24432320
TI  - Differences in metabolic profiles of planktonic and biofilm cells in
      Staphylococcus aureus - (1)H Nuclear Magnetic Resonance search for candidate
      biomarkers.
AB  - Staphylococcus aureus is responsible for many types of infections related to
      biofilm presence. As the early diagnostics remains the best option for prevention
      of biofilm infections, the aim of the work presented was to search for
      differences in metabolite patterns of S. aureus ATCC6538 biofilm vs. free
      swimming S. aureus planktonic forms. For this purpose, Nuclear Magnetic Resonance
      (NMR) spectroscopy was applied. Data obtained were supported by means of Scanning
      Electron Microscopy, quantitative cultures and X-ray computed microtomography.
      Metabolic trends accompanying S. aureus biofilm formation were found using
      Principal Component Analysis (PCA). Levels of isoleucine, alanine and 2,3
      butanediol were significantly higher in biofilm than in planktonic forms, whereas
      level of osmoprotectant glycine-betaine was significantly higher in planktonic
      forms of S. aureus. Results obtained may find future application in clinical
      diagnostics of S. aureus biofilm-related infections. 

PMID- 24432321
TI  - Analysis of ciprofloxacin and gentamicin diffusion in Proteus mirabilis O18
      biofilm by laser interferometry method.
AB  - Laser interferometry is a measurement technique used in physical sciences, with a
      potential for new applications in microbiology. Our previously studies, focused
      on the quantitative analysis of antibiotics diffusion through membranes or their
      releasing from gel structure, indicate that this method might be useful in
      analysis of substances diffusion across the bacterial biofilms. As antibiotic -
      biofilm interaction model, we tested above method for determination of
      ciprofloxacin or gentamicin diffusion through Proteus mirabilis O18 biofilm.
      Laser interferometry analysis of antibiotics diffusion showed that the amount of
      ciprofloxacin transported through mature biofilm is 1.9 times higher than
      gentamicin. It was correlated with lower level of gentamicin in compare to the
      level of ciprofloxacin in biofilm, which amounts were predicted in biofilm during
      diffusion process by laser interferometry method. We suggest that the analysis of
      antibiotic diffusion in biofilm might by helpful in evaluation of effectiveness
      of antibacterial agents. 

PMID- 24432322
TI  - The use of infrared spectroscopy and artificial neural networks for detection of
      uropathogenic Escherichia coli strains' susceptibility to cephalothin.
AB  - BACKGROUND & AIMS: Infrared spectroscopy is an increasingly common method for
      bacterial strains' testing. For the analysis of bacterial IR spectra, advanced
      mathematical methods such as artificial neural networks must be used. The
      combination of these two methods has been used previously to analyze taxonomic
      affiliation of bacteria. The aim of this study was the classification of
      Escherichia coli strains in terms of susceptibility/resistance to cephalothin on
      the basis of their infrared spectra. The infrared spectra of 109 uropathogenic E.
      coli strains were measured. These data are used for classification of E. coli
      strains by using designed artificial neural networks. RESULTS: The most efficient
      artificial neural networks classify the E. coli sensitive/resistant strains with
      an error of 5%. CONCLUSIONS: Bacteria can be classified in terms of their
      antibiotic susceptibility by using infrared spectroscopy and artificial neural
      networks.

PMID- 24432323
TI  - Antibiotics sensitivity of Candida clinical and food-borne isolates.
AB  - Candida is a yeast species recognized as the most frequent etiological agent of
      systemic and invasive thrush in humans. Invasions can affect all tissues, organs
      and systems of human in various stages of development. In the last 10 years
      Candida infections have increased 15 times. The purpose of our study was to
      determine the sensitivity of four antibiotics belonging to three different groups
      of antifungal agents against clinical and food-borne Candida strains. Our studies
      showed that of all tested strains, 7% was resistant to nystatin, 32% to
      fluconazole, 23% to voriconazole, and no strains grew in the presence of
      caspofungin. Despite the differences in biochemical profiles of clinical and food
      borne isolates of Candida, a group of strains showing resistance to antibiotics
      include both types of isolates. At the same time circulating of antibiotic
      resistant strains outside the hospital environment and the yeast infection via
      food is possible. 

PMID- 24432324
TI  - Phosphorus cycle - possibilities for its rebuilding.
AB  - The rebuilding of the phosphorus cycle can be performed with the use of both
      biotechnology and chemical technology. This paper presents a review of the
      phosphorus cycle and the different approaches that can be taken to the recovery
      of phosphorus from phosphate-rich waste. Critical issues in the phosphorus cycle
      are also discussed. Methods for the recovery of phosphorus form sewage sludge ash
      are widely explored and divided into two groups: wet extraction methods and
      thermochemical methods. Laboratory-scale methods are described, as well as
      proposed industrial technologies, with particular regard to the possibilities for
      their implementation in Poland. Phosphorus recovery methods from SSA (sewage
      sludge ash) in our country seems to be promising due to the increasing number of
      sewage sludge incineration plants, which could easily supply ash to future
      recovery installations. For the effective recovery of P from sewage sludge ash,
      it is essential to make the right choice in determining the appropriate method to
      use with respect to the particular properties of the ash composition available. A
      patented method of phosphorus recovery by acid extraction methods, developed by
      Cracow University of Technology, results in an efficiency of 80-96% for
      phosphorus recovery. 3000 to 4000 tons of phosphorus per year can be recycled and
      introduced back into the environment, that covers around 7% of the total amount
      of phosphorus ore imported into Poland between 2008 and 2009. 

PMID- 24432325
TI  - Production of triterpenoids with cell and tissue cultures.
AB  - Triterpenes are group of biologically active compounds which can be found in
      higher plants. Their main source are plants bark, leaves, twigs, fruits, resins
      or oils. The biological activity of triterpens is very diversified and many
      studies have already confirmed the following therapeutic effects: anti
      inflammatory, antimicrobial, antiviral, antifungial, immunomodulatory, and
      hepatoprotective. Synthesis of triterpenes derivates can be performed by chemical
      or enzymatic reactions, however biotransformation is more specific and eliminates
      the side products and the molecule alterations. These processes use isolated
      enzymes or microorganisms. Cell culture in vitro eliminates problems like extract
      variability as well as instability of the compounds being obtained during the
      extraction process. What is more, it ensures high reproducibility and optimal
      regio- and enantioselectivity. The most widely used technique is a classical
      screening of a series of microbial strains. Studies on triterpene
      biotransformation give a lot of information about new biologically active
      compounds and let predict the metabolism of biological compounds. This review
      presents most important advancements in the metabolic engineering of
      microorganisms for the production of triterpenoids. Moreover, the review
      highlights general strategies to obtain rich biochemical diversity of plants by
      employing the biocatalysts produced by microorganisms or tissue cultures. 

PMID- 24432326
TI  - The use of oak chips and coconut fiber as biofilter media to remove vocs in
      rendering process.
AB  - The study evaluated the effectiveness of air biofiltration in rendering plants.
      The biofilter material comprised compost soil (40%) and peat (40%) mixed up with
      coconut fiber (medium A) and oak bark (medium B). During biofiltration average
      VOCs reduction reached 88.4% for medium A and 89.7% for medium B. A positive
      relationship of aldehyde reduction from material humidity (r = 0.502; alpha<0.05)
      was also noted. Other biomaterial parameters did not affect the treatment
      efficiency. 

PMID- 24432327
TI  - Intra-population genetic diversity of cultivated carrot (Daucus carota L.)
      assessed by analysis of microsatellite markers.
AB  - Intra-population variation of 18 cultivated carrot (Daucus carota L. ssp.
      sativus) populations of diverse origins was evaluated using codominant
      microsatellite (SSR) markers. Using 27 genomic and EST-derived SSR markers, 253
      alleles were identified with a mean 9.4 alleles per marker. Most of the alleles
      (60.5%) were rare i.e., with the frequency <= 0.05 while only 3.95% of alleles
      occurred with frequency > 0.6. EST-derived SSR markers were less polymorphic than
      genomic SSR markers. Differences in allele occurrence allowed 16 out of 18
      populations to be assigned to either the Western or Asian carrot gene pools with
      high probability. Populations could be also discriminated due to the presence of
      private alleles (25.3% of all alleles). Most populations had excess of alleles in
      the homozygous state indicating their inbreeding, although heterozygous loci were
      common in F1 hybrids. Genetic diversity was due to allelic variation among plants
      within populations (62% of total variation) and between populations (38%).
      Accessions originating from continental Asia and Europe had more allelic variants
      and higher diversity than those from Japan and USA. Also, allelic richness and
      variability in landraces was higher than in F1 hybrids and open-pollinated
      cultivars. 

PMID- 24432328
TI  - Genetic polymorphism of Hucul horse population based on 17 microsatellite loci.
AB  - Short tandem repeat (STR) loci, i.e. microsatellites are a class of genetic
      markers commonly used for population studies and parentage control. This study
      determined the usefulness of microsatellite markers recommended by International
      Society for Animal Genetics (ISAG) for identification and pedigree analysis in
      horses based on the example of Polish Hucul horse population (Equus caballus).
      The set of seventeen microsatellites loci was tested (AHT4, AHT5, ASB2, HMS2,
      HMS3, HMS6, HMS7, HTG10, HTG4, HTG6, HTG7, VHL20, ASB17, ASB23, CA425, HMS1,
      LEX3) for 216 individuals. All samples were genotyped and mean number of alleles
      per locus was estimated (7.00). Means of observed (Ho) and expected (He)
      heterozygosity were calculated 0.7288 and 0.7027, respectively. The observed
      heterozygosity was similar to the results of research on Hucul horse population
      in another area of Carpathians Mountains. The average polymorphism information
      content (PIC) for analyses of seventeen microsatellite markers indicates the
      usefulness of this set of markers for Hucul horse parentage testing. 

PMID- 24432329
TI  - Phenolics, antioxidative activity and characterization of anthocyanins in berries
      of blackcurrant interspecific hybrids.
AB  - The interest in phenols and anthocyanins has increased due to their antioxidant
      properties and to their potential usage as dietary antioxidants in human
      nutrition. Total phenols and anthocyanin content, composition and stability in
      berry extracts of blackcurrant interspecific hybrids, and antioxidative activity
      of extracts was evaluated. Berries of interspecific hybrids accumulated 530 to
      614 mg 100 g(-1) FW of total phenolic compounds, while 621 mg 100 g(-1) FW of
      phenolics was established in berries of control Ribes nigrum cultivar 'Ben
      Tirran'. 'Ben Tirran' berries accumulated 444 mg 100 g(-1) FW of anthocyanins and
      higher amount was identified in berries of interspecific hybrids No. 11-13 (R.
      nigrum * R. petraeum) and No. 57 (R. nigrum * R. aureum), 522 and 498 mg100 g(-1)
      FW respectively. Berry extracts of hybrid No. 11-13 distinguished by the highest
      antioxidative activity (80%) and it was higher than antioxidant activity of 'Ben
      Tirran' (70%). Antioxidative activity of all tested berry extracts (70-80%) was
      twice higher compared to synthetic antioxidant BHT (39%). However correlation
      between phenolics or total anthocyanin content and antioxidative activity degree
      was not established. Amount of cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside
      in berries of hybrids No. 57, No. 11-13 and No. 8 ((R. nigrum * R. americanum) *
      (R. nigrum * R. americanum)) was higher than in berries of 'Ben Tirran'. It was
      established that cyanidins are more stable anthocyanins in all studied
      temperature and irradiation conditions. Therefore interspecific hybrids No. 57
      and No. 11-13 were the most agronomically valuable hybrids. 

PMID- 24432330
TI  - Influence of process parameters on properties of Nanostructured Lipid Carriers
      (NLC) formulation.
AB  - Nanostructured lipid carriers (NLC) are stable colloidal formulations with
      notable advantages for drug delivery systems. Thanks to their physicochemical
      stability, biocompatibility, biodegradability and controlled drug release, they
      have received increasing attention for the last several years. The aim of the
      study was to prepare and characterize nanostructured lipid carriers (NLC). Both,
      the effect of the process parameters and the effect of the preemulsion
      composition on the NLC properties were investigated. In the work, different type
      of surfactants (i.e. decyl glucoside, Poloxamer188, Tween 80, sodium cholate) and
      their combinations were used to stabilize NLC dispersions. Moreover, several
      kinds of solid lipids (modified beeswax, gliceryl behenate, cetyl palmitate and
      berry wax) and liquid lipids (caprilic/capric triglyceride and decyl oleate) were
      applied. An ultrasonication method using a probe type sonicator was used to
      obtain NLC, and the time and energy of the process were modified throuhout. The
      physicochemical properties of the formulations, such as particle size, size
      distribution, polidispersity index were studied using the dynamic light
      scattering (DLS) method. The electrophoretic mobility of obtained particles was
      also measured, using the Zetasizer Nano ZS Malvern Instrument based on the Laser
      Doppler Velocimetry (LDV) technique. Knowing the value of electrophoretic
      mobility of particles for given conditions, the zeta potential was determined.
      The obtained results showed that the process parameters and the composition of
      the preemulsion had significant impact on the nanoparticles structure. The
      optimal formulations size ranged between 60 and 80 nm, and the value of their
      zeta potential was up to -30mV. The stability of these systems was further
      confirmed by macroscopic observation. 

PMID- 24432331
TI  - Studies on the formation of O/W nano-emulsions, by low-energy emulsification
      method, suitable for cosmeceutical applications.
AB  - The formation of oil/water (O/W) nano-emulsions suitable for cosmeceutical
      application was studied. Nano-emulsions were prepared by using phase inversion
      composition (PIC) method, one of the low-energy emulsification methods. The
      process consist of stepwise water addition to oil/surfactant mixture, at T = 25
      degrees C. Caprylic/capric triglycerides (GTCC), propylene glycol
      dicaprylate/dicaprate (PC) and oleic acid (OA) were applied as an oil phase.
      Polysorbate 80 was used as the surfactant. Kinetic stability of the nano
      emulsions was analyzed by measuring droplet size as a function of time for
      different oil/surfactant ratio. The particles size distribution was analyzed by
      means DLS measurement technique (Dynamic Light Scattering), using Zetasizer Nano
      ZS (Malvern Instruments, UK). One of triterpenoic acid, practically non-water
      soluble substance was selected as an active and incorporated into the stable
      formulation. The obtained results proved that the nanoemulsion NE-T80-GTCC-20:80
      based on caprylic/capric triglycerides with the oil/surfactant ratio O/S = 2 0:80
      and the droplet size r = 25 nm was the most stable one and additionally showed
      the highest solubilisation capacity for the triterpene. 

PMID- 24432332
TI  - Genetic polymorphisms of leptin and leptin receptor genes in relation with
      production and reproduction traits in cattle.
AB  - Leptin and leptin receptor genes are considered as production traits markers in
      dairy or beef cattle. The aim of this study was to verify the associations of
      polymorphisms in bovine LEP and LEPR genes with production and reproduction
      traits in Slovak Spotted and Pinzgau cows. Long-life production was evaluated:
      milk, protein, and fat yield and reproduction traits: age at first calving,
      calving interval, days open, and insemination interval. In total, 296 blood
      samples of Slovak Spotted and 85 hair roots samples of Pinzgau cows were
      analyzed. In order to detect LEP/Sau3AI (BTA 4, inron 2) and LEPR/T945M (BTA 3,
      exon 20) genotypes PCR-RFLP method was used. In Slovak Spotted and Pinzgau cows
      allele frequencies were 0.838/0.162 and 0.694/0.306 for A and B LEP variants, and
      0.954/0.046 and 0.912/0.088 for C and T LEPR variants, respectively. For testing
      the associations between SNPs LEP/Sau3AI and LEPR/T945M and evaluated traits, the
      General Linear Model procedure in SAS Software was used. Statistical analysis
      showed that SNP LEP/Sau3AI significantly affected milk, protein and fat yield
      (P<0.05), and age at first calving (P<0.01) in analyzed population of cows.
      Statistically, SNP LEPR/T945M affected significantly calving interval (P<0.01)
      only. Results of our study suggest that especially leptin is a candidate gene,
      which influences mainly milk production traits and might be implemented in
      breeding strategies to improve the production performance of both analyzed cattle
      breeds. 

PMID- 24432333
TI  - Bioavailability of hydrocarbons to bacterial consortia during Triton X-100
      mediated biodegradation in aqueous media.
AB  - The aim of our study was to investigate the effect of Triton X-100 on the
      biodegradation efficiency of hexadecane and phenanthrene carried out by two
      bacterial consortia. It was established that the tested consortia were not able
      to directly uptake compounds closed in micelles. It was observed that in micellar
      systems the nonionic synthetic surfactant was preferentially degraded (the
      degradation efficiency of Triton X-100 after 21 days was 70% of the initial
      concentration - 500 mg/l), followed by a lesser decomposition of hydrocarbon
      released from the micelles (30% for hexadecane and 20% for phenanthrene).
      However, when hydrocarbons were used as the sole carbon source, 70% of hexadecane
      and 30% of phenanthrene were degraded. The degradation of the surfactant did not
      contribute to notable shifts in bacterial community dynamics, as determined by
      Real-Time PCR. The obtained results suggest that if surfactant-supplementation is
      to be used as an integral part of a bioremediation process, then possible
      bioavailability decrease due to entrapment of the contaminant into surfactant
      micelles should also be taken into consideration, as this phenomenon may have a
      negative impact on the biodegradation efficiency. Surfactant-induced mobilization
      of otherwise recalcitrant hydrocarbons may contribute to the spreading of
      contaminants in the environment and prevent their biodegradation. 

PMID- 24432334
TI  - Nanosilver against fungi. Silver nanoparticles as an effective biocidal factor.
AB  - The work presents a method of obtaining an aqueous raspberry extract as well as
      its physicochemical and analytical characteristics. The paper also contains a
      description of the method of preparation of nanosilver suspensions based on this
      extract. The raspberry extract served as a source of phenolic compounds which
      acted as both reducing and stabilizing agents. Suspensions of silver
      nanoparticles were obtained with the use of chemical reduction method. The silver
      ions concentration, pH value and temperature of samples incubation were
      independent variables. The next step of the research was to measure the
      antifungal activity of the received silver nanoparticles as well as to perform a
      mycological efficacy resistance analysis of the tested preparations in relation
      to different concentrations of nanostructured silver. Tests were conducted in
      compliance with the Eucast guidelines. The results of microbiological study of
      (the samples') biocidal effect against Cladosporium cladosporoides and
      Aspergillus niger are described. It was found that using nanosilver suspension at
      the concentration of 50 ppm inhibited the growth of Cladosporium cladosporoides
      and Aspergillus niger by 90% and 70%, respectively. 

PMID- 24432335
TI  - Analysis of Slovak Spotted breed for bovine beta casein A1 variant as risk factor
      for human health.
AB  - The goal of work was identification A1 variant of bovine beta casein which
      involves ischemic heart disease and diabetes mellitus in human. The digestion of
      A1beta casein can result in the production of bioactive beta casomorphin-7 (BCM
      7); this is not the case with A2. This bioactive peptide has been linked to
      physiological traits that may elicit effects on components of the vascular and
      immune systems. The material involved 111 Slovak Spotted breed. Bovine genomic
      DNA was extracted from whole blood by using commercial kit, and used in order to
      estimate beta-casein genotypes by means of PCR-RFLP method. The PCR products were
      digested with DdeI restriction enzyme. In the population included in the study
      were detected all three genotypes, homozygote genotype A1A1 (14 animals),
      heterozygote genotype A1A2 (37 animals) and homozygote genotype A2A2 (60
      animals). In the total population of cattle homozygotes A2A2-0.5405 were the most
      frequent, while homozygotes A1A1-0.1261 were the least frequent ones. This
      suggests a superiority of allele A2 (0.7072) which does not produce BCM-7, and
      thus is safe for human consumption. The expected homozygosity for gene CSN2 is in
      the population stated a slight increase in homozygosity (0.5858). This caused a
      slight decrease in the level of possible variability realization (41.80%), which
      corresponds to the effective number of alleles (1.7071). 

PMID- 24432336
TI  - Micelle-mediated extraction of elderberry blossom by whey protein and naturally
      derived surfactants.
AB  - Classical methods of the extraction of active ingredients from the plant material
      are expensive, complicated and often environmentally unfriendly. The micelle
      mediated extraction method (MME) seems to be a good alternative. In this work,
      extractions of elderberry blossoms (Flos Sambuci) were performed using MME
      methods. Several popular surfactants and whey protein concentrate (WPC) was
      applied in the process. The obtained results were compared with those obtained in
      extraction by means of water. Antioxidant properties of the extracts were
      analyzed by using two different methods: reaction with di(phenyl)-(2,4,6
      trinitrophenyl)iminoazanium (DPPH) reagent and Follin's method. Furthermore, the
      flavonoid content in the extracts was determined. The results confirmed that the
      MME method with using whey protein might be an alternative method for obtaining,
      rich in natural antioxidants, plant extracts. 

PMID- 24432337
TI  - Genetic diversity in populations of Slovak Spotted cattle based on single
      nucleotide polymorphisms analyses.
AB  - The aim of this study was to identify SNPs in leptin (LEP), leptin receptor
      (LEPR) and growth hormone (GH) genes in order to analyze genetic diversity of
      Slovak Spotted cattle. The total numbers of blood samples were taken from 353
      Slovak Spotted cows originating from four farms. Genomic DNA was isolated by
      phenol-chloroform extraction method and analyzed by PCR-RFLP method. After
      digestion with restriction, enzymes were detected in whole population of cow's
      alleles with frequency: LEP/Sau3AI A 0.84 and B 0.16 (+/-0.0152); LEPR/BseGI C
      0.95 and T 0.05 (+/-0.0089) and GH/AluI L 0.70 and V 0.30 (+/-0.0188). Based on
      the observed vs. expected genotypes frequencies populations across loci were in
      Hardy-Weinberg equilibrium (P?>0.05). Predominant for SNP LEP/Sau3AI was AA
      genotype (0.70), for SNP LEPR/T945M CC genotype (0.91), and LL genotype (0.48)
      was most frequent for SNP GH/AluI. The observed heterozygosity of SNPs across
      populations was also transferred to the low or median polymorphic information
      content 0.24 (He 0.28), 0.08 (He 0.09) and 0.33 (He 0.47) for LEP, LEPR and GH
      genes, respectively. Within genetic variability estimating negative values of
      fixation indexes FIS (-0.09-0.05) and FIT (-0.07-0.03) indicating heterozygote
      excess were observed. The value of FST indexes (0.018-0.023) shows very low
      levels of genetic differentiation in allele frequencies of loci among evaluated
      subpopulations. The low values of genetic distances (0.0018-0.0159) indicated
      high genetic relatedness among animals in subpopulations caused probably by
      common ancestry used in breeding program at farms. 

PMID- 24432338
TI  - Identification of lipid derivatives in Hep G2 cells.
AB  - Metabolism of polyunsaturated fatty acids results in biosynthesis of mediators
      with different physiological effects. These metabolites include prostaglandins,
      prostacyclins, isoprostanes and others that are important signalling molecules
      and regulate a variety of physiological and pathophysiological processes
      including inflammation. Prostaglandins and isoprostanes are produced by either
      non-enzymatic lipid peroxidation or by enzyme-induced peroxidation
      (cyclooxygenases and lipoxygenases). They are used as biomarkers of oxidative
      stress. The aim of our study was to assess the effect of eicosapentaenoic acid
      (EPA) supplementation with added benzo(a)pyrene (BaP) on HepG2 cells by using a
      UHPLC/MS-TOF method. This rapid and simple method was developed for the
      identification, separation and quantification of 8-iPGF3alpha, PGF3alpha, 8
      isoPGF2alpha and 5-iPF2alpha in cultured cells. The UHPLC/MS-TOF method was
      validated. The calculated limit of detection was in the range of 0.16-0.50 ng/mL,
      precision (% RSD): 1.2-2.1% and recoveries better than 88%. This method empowered
      qualitative and quantitative analysis of the selected individual prostaglandins
      derived from arachidonic acid and eicosapentaenoic acid from cell extracts. 

PMID- 24432339
TI  - Oxidative polymerization of lignins by laccase in water-acetone mixture.
AB  - The enzymatic oxidative polymerization of five technical lignins with different
      molecular properties, i.e. Soda Grass/Wheat straw Lignin, Organosolv Hardwood
      Lignin, Soda Wheat straw Lignin, Alkali pretreated Wheat straw Lignin, and Kraft
      Softwood was studied. All lignins were previously fractionated by acetone/water
      50:50 (v/v) and the laccase-catalyzed polymerization of the low molecular weight
      fractions (Mw < 4000 g/mol) was carried out in the same solvent system.
      Reactivity of lignin substrates in laccase-catalyzed reactions was determined by
      monitoring the oxygen consumption. The oxidation reactions in 50% acetone in
      water mixture proceed with high rate for all tested lignins. Polymerization
      products were analyzed by size exclusion chromatography, FT-IR, and (31)P-NMR and
      evidence of important lignin modifications after incubation with laccase. Lignin
      polymers with higher molecular weight (Mw up to 17500 g/mol) were obtained. The
      obtained polymers have potential for applications in bioplastics, adhesives and
      as polymeric dispersants. 

PMID- 24432340
TI  - Development of novel cellular model for affinity studies of histamine H(4)
      receptor ligands.
AB  - The G protein-coupled histamine H4 receptor (H4R) is the last member of histamine
      receptors family discovered so far. Its expression pattern, together with
      postulated involvement in a wide variety of immunological and inflammatory
      processes make histamine H4 receptor an interesting target for drug development.
      Potential H4R ligands may provide an innovative therapies for different immuno
      based diseases, including allergy, asthma, pruritus associated with allergy or
      autoimmune skin conditions, rheumatoid arthritis and pain. However, none of
      successfully developed selective and potent histamine H4 receptor ligands have
      been introduced to the market up to date. For that reason there is still a strong
      demand for pharmacological models to be used in studies on potent H4R ligands. In
      current work we present the development of novel mammalian cell line, stably
      expressing human histamine H4 receptor, with use of retroviral transduction
      approach. Obtained cell line was pharmacologically characterized in radioligand
      binding studies and its utility for affinity testing of potent receptor ligands
      was confirmed in comparative studies with the use of relevant insect cells
      expression model. Obtained results allow for statement that developed cellular
      model may be successfully employed in search for new compounds active at
      histamine H4 receptor. 

PMID- 24432341
TI  - The kinetic reduction of Cr(VI) by yeast Saccharomyces cerevisiae, Phaffia
      rhodozyma and their protoplasts.
AB  - Chromium in the sixth oxidation state may easily penetrate cellular membranes via
      non-specific sulfate transporters due to its tetrahedral symmetry (high
      similarity to SO4(2-) and HPO4(2-)). This feature makes chromium a toxic and
      hazardous pollutant responsible for the deterioration of midland water quality.
      The aim of the study was to evaluate the capacity of two yeast species -
      Saccharomyces cerevisiae and Phaffia rhodozyma - and their protoplasts to reduce
      Cr(VI) to lower oxidation states. The study also deals with the behavior of the
      yeasts upon the presence of elevated sulfate ions as a competitive inhibitor of
      chromate transport by the sulfate transporters. The chromate-reducing activities
      were monitored by determination of Cr(V) free radical form with the use of L-band
      (1.2 GHz) EPR (electron paramagnetic resonance) spectroscopy. It was observed
      that both of the studied yeast strains exhibited the ability to reduce Cr(VI)
      applied at 4 mM. The cells of P. rhodozyma showed about 3.5 times higher
      reduction than S. cerevisiae. The reduction efficiency was significantly improved
      when the protoplasts of both strains were used and reached 100% in the first 10
      minutes of the reduction process which suggests that the cellular wall may have a
      notable influence on the uptake and/or inhibition of chromium reduction process.
      The reduction effect of P. rhodozyma cells and protoplasts may be associated with
      the more sufficient production of metabolites (such as glutathione and cysteine),
      which may also be responsible for the increased tolerance of the strain towards
      high concentrations of toxic chromium. 

PMID- 24432342
TI  - Poly(acrylic acid-co-methyl methacrylate)/metronidazole systems: synthesis and
      complexation.
AB  - We report on preparation of poly(acrylic acid-co-methyl methacrylate) (PAM) micro
      and nanoparticles and, in the subsequent stage, complexation reaction with the
      active substance - metronidazole (MET). The drug release behavior of MET - loaded
      PAM micro- and nanoparticles was evaluated in water and phosphate buffered saline
      (PBS, 0.9% NaCl) at 37oC. It has been found that introduction of MET into PAM
      micro- and nanoparticles enabled gradual and controlled release of the active
      substance. Structural analysis using FT-IR (ATR) and (1)H NMR, as well as surface
      morphology assessment by SEM, were performed. 

PMID- 24432343
TI  - Pig manure treatment by filtration.
AB  - A study of new pig manure treatment and filtration process was carried out. The
      advantage of the worked out technology is the method of incorporation of
      crystalline phase into solid organic part of manure. The obtained new solid phase
      of manure contains about 50% of crystalline phase forming a filtration aid that
      enables high effectiveness of manure filtration. The filtration rate of manure
      separation into solid and liquid fractions with pressure filter may achieve 1300
      3000 kg/m(2)/h. The method makes it possible to maintain an overall average
      pollutant removal performance 90% for the chemical oxygen demand COD, > 99% for
      the suspended solids SS, to 47% for the total nitrogen content. The obtained
      results showed that the proposed technology being efficient and simple offers a
      possible solution to pig manure problems. 

PMID- 24432344
TI  - Changes in the properties of pig manure slurry.
AB  - The paper presents the results of analyses of samples of manure from a pig farm
      located near Pila, Poland performed between June 2011 and May 2012 using a single
      sampling system. The statistical analyses of the average content of chemical and
      biological oxide demands, nitrogen, phosphorus, potassium, calcium and dry mass
      in the slurry in various seasons allowed us to draw conclusions concerning the
      changes in the chemical composition of the manure in specific seasons and to
      determine the correlations between the chemical parameters. The average content
      of N, BOD, P, and dry mass content tended to decrease systematically from the
      spring until the winter. The highest correlation coefficient, which indicates
      significant interdependency among the variables tested, was consistently found
      for COD and BOD, whereas the smallest correlation coefficient was found
      consistently for K and Ca and once for Ca and N. 

PMID- 24432345
TI  - Studies on sintering process of synthetic hydroxyapatite.
AB  - In this study the effect of sintering process in different temperatures on
      microstructure and morphological properties of sintered hydroxyapatite (HAp) was
      investigated. HAp powder was prepared by wet precipitation method from following
      reagents: Ca(OH)2 + H3PO4 in an alkaline conditions. Thermal analysis (TA), X-Ray
      diffraction method (XRD), FT-IR spectrometry (FT-IR) and scanning electron
      microscopy (SEM) were used to elaborate the phase composition and properties of
      sintered HAp samples and raw HAp powder as well. The total and apparent density
      and total porosity of sintered compacts, shrinkage and weight loss during the
      sintering were also measured. The results show that there is a difference in
      sintering behavior of synthetic hydroxyapatites depending on sintering
      temperature. The main differences refer to the loss of mass, shrinkage, changes
      in porosity and density of the investigated materials. 

PMID- 24432346
TI  - Expression of three diadinoxanthin de-epoxidase genes of Phaeodacylum tricornutum
      in Escherichia coli Origami b and BL21 strain.
AB  - In the diadinoxanthin cycle the epoxy group is removed from diadinoxanthin and
      diatoxanthin is created. This conversion takes place e.g. in diatoms with the
      involvement of the enzyme diadinoxanthin de-epoxidase. In one of the diatom
      species, Phaeodactylum tricornutum (CCAP 1055/1 strain with genome sequenced)
      three de-epoxidase genes (PtVDE, PtVDL1, PtVDL2) have been identified, but only
      one of them (PtVDE) corresponds to violaxanthin de-epoxidase, an enzyme which is
      commonly found in higher plants. In these studies, the expression of two de
      epoxidase genes of another Phaeodactylum tricornutum strain (UTEX 646), which is
      commonly used in diatom studies, were obtained in Origami b and BL21 E. coli
      strains. The molecular masses of the mature proteins are about 49 kDa and 60 kDa,
      respectively, for VDE and VDL2. Both enzymes are active with violaxanthin as a
      substrate. 

PMID- 24432347
TI  - Temperature effect on growth, and selected parameters of Phaeodactylum
      tricornutum in batch cultures.
AB  - The effect of optimal and stress temperatures on the growth kinetics of the
      Phaeodactylum tricornutum CCAP/1055/1 strain (a model diatom with a known genome
      sequence) in batch cultures was examined. The analysis of the obtained results
      showed two phases of culture growth. There were significant positive correlations
      between OD increase of chlorophyll a chlorophyll c and protein concentration at
      different temperatures. The Fv/Fm parameter achieved a maximum level on the 6(th)
      or 7(th) day and then decreased to the values registered on the first day of
      observation. Genetic material undergoes gradual degradation 10 days after
      inoculation. The size of the cells was invariable. 

PMID- 24432348
TI  - Arbutin production via biotransformation of hydroquinone in in vitro cultures of
      Aronia melanocarpa (Michx.) Elliott.
AB  - Arbutin (hydroquinone beta-D-glucoside) is a compound of plant origin possessing
      valuable therapeutic (urinary tract disinfection) and cosmetic (skin whitening)
      properties, which can be obtained from in vitro cultures of plants belonging to
      different taxa via biotransformation of exogenously supplemented hydroquinone.
      Agitating cultures of Aronia melanocarpa were maintained on the Murashige and
      Skoog medium containing growth regulators: the cytokinin - BAP (6
      benzylaminopurine), 2 mg/l and the auxin NAA (alpha-naphthaleneacetic acid), 2
      mg/l. The biomass was cultured for 2 weeks and then hydroquinone was supplemented
      at the following doses: 96, 144, 192, 288 and 384 mg/l either undivided or
      divided into two or three portions added at 24-hour intervals. The content of the
      reaction product - arbutin, was determined using an HPLC method in methanolic
      extracts from biomass and lyophilized medium samples collected 24 hours after the
      addition of the last precursor dose. The total amounts of arbutin were very
      diverse, from 2.71 to 8.27 g/100g d.w. The production of arbutin rose with
      increasing hydroquinone concentration. The maximum content of the product was
      observed after hydroquinone addition at 384 mg/l divided into two portions.
      Biotransformation efficiency also varied widely, ranging from 37.04% do 73.80%.
      The identity of the product - arbutin, after its isolation and purification was
      confirmed by spectral analysis ((1)H-NMR spectrum). The maximum amount of arbutin
      obtained was higher than that required by the latest 9(th) Edition of the Polish
      Pharmacopoeia and by the newest 8th Edithion of European Pharmacopoeia for Uvae
      ursi folium (7.0 g/100g d.w.), and is interesting from practical point of view. 

PMID- 24432349
TI  - Prp4 kinase is required for proper segregation of chromosomes during meiosis in
      Schizosaccharomyces pombe.
AB  - Chromosome segregation during meiosis is a complex process, which leads to
      production of four haploid gametes from two precursor cells. Reversible
      phosphorylation of proteins plays a crucial role in this process. The
      Schizosaccharomyces pombe Prp4 is an essential serine/threonine protein kinase,
      which belongs to the Clk/Sty family. To study the role of Prp4 in meiosis, we
      analysed chromosome segregation in a strain carrying conditional analog-sensitive
      allele of Prp4 protein kinase (prp4-as2). Our data show, that Prp4 protein kinase
      plays important role in chromosome segregation during meiosis, as revealed by
      enhanced missegregation of chromosomes in prp4-as2 mutant cells. 

PMID- 24432350
TI  - The influence of communicative relations on facial responses to pain: does it
      matter who is watching?
AB  - BACKGROUND: Facial responses to pain are believed to be an act of communication
      and, as such, are likely to be affected by the relationship between sender and
      receiver. OBJECTIVES: To investigate this effect by examining the impact that
      variations in communicative relations (from being alone to being with an intimate
      other) have on the elements of the facial language used to communicate pain
      (types of facial responses), and on the degree of facial expressiveness. METHODS:
      Facial responses of 126 healthy participants to phasic heat pain were assessed in
      three different social situations: alone, but aware of video recording; in the
      presence of an experimenter; and in the presence of an intimate other.
      Furthermore, pain catastrophizing and sex (of participant and experimenter) were
      considered as additional influences. RESULTS: Whereas similar types of facial
      responses were elicited independent of the relationship between sender and
      observer, the degree of facial expressiveness varied significantly, with
      increased expressiveness occurring in the presence of the partner. Interestingly,
      being with an experimenter decreased facial expressiveness only in women. Pain
      catastrophizing and the sex of the experimenter exhibited no substantial
      influence on facial responses. CONCLUSION: Variations in communicative relations
      had no effect on the elements of the facial pain language. The degree of facial
      expressiveness, however, was adapted to the relationship between sender and
      observer. Individuals suppressed their facial communication of pain toward
      unfamiliar persons, whereas they overtly displayed it in the presence of an
      intimate other. Furthermore, when confronted with an unfamiliar person, different
      situational demands appeared to apply for both sexes.

PMID- 24432351
TI  - Paper spray mass spectrometry-based method for analysis of droplets in a gravity
      driven microfluidic chip.
AB  - This work presents a paper spray mass spectrometry-based method, to analyze
      microdroplets produced in a gravity-driven microchip. Droplets at ambient
      pressure were passively transferred from the chip to a paper substrate by the
      capillary wicking effect. Paper spray ionization was then performed for mass
      spectrometry (MS) analysis of droplet contents. The qualitative and quantitative
      analytical performances of this technique for single droplets were demonstrated.
      This manually controlled interface is straightforward, low-cost and simple to
      implement. Moreover, paper spray ionization MS holds promise in the direct
      analysis of real biological/chemical microreaction samples because of its
      tolerance with complex matrices. As a proof-of-concept example, the droplet-based
      acetylcholine hydrolysis was carried out to demonstrate the validation of our
      method for the direct analysis of micro-chemical/biological reactions. We also
      introduced a flow injection analysis (FIA) system combined with our droplet
      system to generate a concentration gradient. As a result, the microreaction can
      be performed at different concentrations and kinetic information can be obtained
      in one sample injection. In conclusion, the combination of a microdroplet chip
      with paper spray ionization and the introduction of the FIA system and make our
      droplet-MS scheme a useful platform for monitoring and analyzing organic-phase
      chemical/biological reactions. 

PMID- 24432352
TI  - Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker.
AB  - Protoporphyrin IX (PPIX), a derivative of hematoporphyrin, can accumulate in
      rapidly growing tissues, including tumors and atherosclerotic plaques. The
      objective of this study is to employ PPIX fluorescence to detect the changes in
      blood caused by the formation of atheromatous plaques in arteries; this
      measurement can function as a liquid biopsy. For this purpose twenty four rabbits
      were randomly divided into groups: control group (CG)--fed with a normal diet,
      and an experimental group (EG)--fed with a hypercholesterolemic diet (1%
      cholesterol). Blood samples were collected before (0 time) and after 22, 43, 64
      days to measure biochemical factors. The aortas were removed after 22, 43 and 64
      days to assess the atherosclerotic plaques. PPIX was extracted from the blood and
      fluorescence was measured in the 550-750 nm range from samples that were excited
      at 405 nm. Aminolevulinic acid (ALA) was administered intravenously to increase
      the PPIX fluorescence intensity in the arteries and consequently in the liquid
      biopsy of the atherosclerotic plaques. The results have shown that the PPIX
      fluorescence increased as the atheromatous plaques grew. The aorta fluorescence
      and the PPIX fluorescence increased in the animals in the experimental group that
      received ALA. PPIX that accumulates in atheromatous plaques transfers to the
      blood and can be analyzed by extracting porphyrin from total blood. Therefore,
      this method can aid in the early diagnosis of atherosclerosis with high
      sensitivity.

PMID- 24432353
TI  - Single nanoparticle detection using photonic crystal enhanced microscopy.
AB  - We demonstrate a label-free biosensor imaging approach that utilizes a photonic
      crystal (PC) surface to detect surface attachment of individual dielectric and
      metal nanoparticles through measurement of localized shifts in the resonant
      wavelength and resonant reflection magnitude from the PC. Using a microscopy
      based approach to scan the PC resonant reflection properties with 0.6 MUm spatial
      resolution, we show that metal nanoparticles attached to the biosensor surface
      with strong absorption at the resonant wavelength induce a highly localized
      reduction in reflection efficiency and are able to be detected by modulation of
      the resonant wavelength. Experimental demonstrations of single-nanoparticle
      imaging are supported by finite-difference time-domain computer simulations. The
      ability to image surface-adsorption of individual nanoparticles offers a route to
      single molecule biosensing, in which the particles can be functionalized with
      specific recognition molecules and utilized as tags. 

PMID- 24432354
TI  - The first decade of organic spintronics research.
AB  - The first decade of organic spintronics research has benefitted from the analogy
      and previous experience of the inorganic spintronics field, coupled with the
      unlimited versatility of organic materials synthesis. At the same time, the field
      of organic spintronics has developed into an attractive and promising field of
      its own, with rich physics and promising unique potential applications. We review
      here a set of significant milestones achieved in organic spintronic devices such
      as organic spin valves, bipolar spin-valves, and hybrid organic/inorganic light
      emitting diodes in comparison with representative inorganic spintronic devices.
      We also point out acute problems that need to be resolved before the young field
      of organic spintronics can mature. 

PMID- 24432355
TI  - Behavioural and physiological expression of arousal during  decision-making in
      laying hens.
AB  - Human studies suggest that prior emotional responses are stored within the brain
      as associations called somatic markers and are recalled to inform rapid decision
      making. Consequently, behavioural and physiological indicators of arousal are
      detectable in humans when making decisions, and influence decision outcomes. Here
      we provide the first evidence of anticipatory arousal around the time of decision
      making in non-human animals. Chickens were subjected to five experimental
      conditions, which varied in the number (one versus two), type (mealworms or empty
      bowl) and choice (same or different) of T-maze goals. As indicators of arousal,
      heart-rate and head movements were measured when goals were visible but not
      accessible; latency to reach the goal indicated motivation. We found a greater
      increase in heart-rate from baseline to the goal-viewing period, more head
      movements and shorter latencies in all conditions including mealworms compared to
      those with empty bowls. More head movements when two mealworm bowls were
      available compared to just one, and prior to occasions when hens accessed an
      empty bowl rather than declining to move, showed that arousal preceded and
      influenced decision-making. Our results provide an important foundation for
      investigating arousal during animal decision-making and suggest that the somatic
      marker hypothesis might not only apply to humans.

PMID- 24432356
TI  - Effect of hydration on the tactile and thermal sensitivity of the lip.
AB  - The vermilion lip is a body site particularly susceptible to water loss.
      Therefore, the role of hydration in tactile perception at the lip was
      investigated. A series of measures of tactile performance and response were
      obtained from 22 female subjects, namely: (1) the subjective assessment of lip
      feel, (2) tactile sensitivity, (3) spatial acuity, (4) thermal sensitivity, and
      (5) the subjective assessment of thermal stimulation. These measures were
      obtained from lips in their natural (untreated) state, and lips that had been
      treated using a hydrating preparation. The preparation altered the subjective
      feel of the lips consistent with the treatment increasing lip hydration and
      compliance. Hydrated lips showed greater sensitivity to light touch, and there
      was a trend toward the lip's thermal sensitivity being altered consistent with
      the lip treatment having a physical cooling effect. Spatial acuity was unaltered
      by the state of lip hydration. The sensitivity changes on hydration were proposed
      to have mechanical basis.

PMID- 24432357
TI  - Photoperiodic effects on reproductive development in male  cavies (Cavia aperea).
AB  - Age at maturity is a particularly important life history parameter, as it
      predicts potential life time reproductive success in many small mammal species.
      Animals should therefore optimize the timing of maturation by reacting to
      environmental stimuli that predict future environmental conditions. Photoperiod
      often reliably predicts ecological conditions. Animals born into a photoperiod
      indicating favorable conditions (spring, summer) may mature earlier and at a
      lower weight than animals born into conditions indicating unfavorable conditions
      (autumn, winter). So far most work was done on small, altricial rodent species
      and we still lack knowledge about their precocial relatives. Precocial animals
      are born much further developed than altricials and might show less plasticity in
      their ontogenetic trajectory than the latter. We tested the influence of
      photoperiod simulated by increasing (spring) or decreasing (autumn) light in
      climate chambers on important life history parameters in a medium sized rodent,
      the highly precocial cavy (Cavia aperea). We wanted to determine whether
      photoperiod influences timing of maturation and early growth in male cavies and
      whether patterns of testosterone in blood are reflected by patterns of
      testosterone metabolites in feces.Males born into simulated spring grew faster
      and matured at an earlier age than males born into simulated autumn conditions.
      Patterns of testosterone in blood correlated with testosterone metabolites
      measured in feces. Male cavies strongly react to predictive photoperiod cues by
      adjusting growth and timing of maturation as we found previously for females,
      corroborating the importance of seasonal cues for adjustments of life history.

PMID- 24432358
TI  - Functional significance of ultraviolet feeding cues in wild turkeys.
AB  - Most birds are able to sense ultraviolet (UV) visual signals. Ultraviolet
      wavelengths are used for plumage signaling and sexual selection among birds. The
      aim of our study was to determine if UV cues are also used for the process of
      food selection in wild turkeys (Meleagris gallopavo). We used avoidance
      conditioning to test the hypothesis that UV feeding cues can be used functionally
      for foraging behavior in wild turkeys. Female turkeys exhibited no avoidance of
      untreated food and 75-98% avoidance of food treated with an UV-absorbent,
      postingestive repellent (0.5-4% anthraquinone; wt./wt.) during repellent
      exposure. Male turkeys exhibited 78-99% avoidance of food treated with 0.5-4%
      anthraquinone. Female and male turkeys that consumed more than 200 mg and 100 mg
      of anthraquinone, respectively, subsequently avoided food treated only with an UV
      absorbent cue. In contrast, unconditioned females consumed 58% more food treated
      with the UV-absorbent cue than untreated food. Thus, wild turkeys do not prefer
      foods associated with UV wavelengths regardless of feeding experience. We also
      observed 1) a weak negative correlation between body condition and intestinal
      parasite infection and 2) moderate, positive correlations between consumption of
      food treated with the conditioned UV cue and intestinal parasite infection among
      male turkeys. The UV feeding cue was used to maintain food avoidance during the
      four days subsequent to postingestive conditioning. Moreover, the consequences of
      consuming food treated with the postingestive, UV-absorbent repellent were
      necessary for conditioned avoidance of the UV-absorbent cue. These findings
      suggest functional significance of UV feeding cues for avian foraging behavior,
      the implications of which will enable subsequent investigations regarding the
      sensory physiology and behavioral ecology of wild birds.

PMID- 24432359
TI  - Running-based taste aversion learning in five strains of rats.
AB  - Although it is well known that voluntary wheel running works as an effective
      unconditioned stimulus to cause conditioned taste aversion (CTA) in several
      strains of rats, there is no study that explores strain differences in running
      based CTA. The present study examines this issue with regard to five frequently
      used rat strains. Experiment 1 compared Sprague-Dawley versus Wistar rats from
      two suppliers, with the target taste being salty (NaCl + MSG) and then sweet
      (saccharin). Experiments 2, 3, and 4 tested rats of Wistar versus Long-Evans,
      Lewis versus Fischer, and Sprague-Dawley versus Lewis strains, respectively, with
      sweet and then salty solutions. None of the experiments showed any reliable
      strain differences in the strength of running-based CTA, suggesting the
      robustness of this learning phenomenon.

PMID- 24432361
TI  - Identifying preferred habitats of samango monkeys (Cercopithecus (nictitans)
      mitis erythrarchus) through patch use.
AB  - To examine habitat preferences of two groups of samango monkeys (Cercopithecus
      (nictitans) mitis erythrarchus) in the Soutpansberg, South Africa, we used
      experimental food patches in fragments of tall forest and in bordering secondary
      growth short forest. Additionally, to test for the impacts of group cohesion and
      movement on habitat use, we tested for the interaction of space and time in our
      analyses of foraging intensity in the experimental food patches placed throughout
      the home ranges of the two groups. We expected the monkeys to harvest the most
      from patches in tall forest habitats and the least from patches in short forest.
      Further, because the monkeys move through their habitats in groups, we expected
      to see group cohesion effects illustrated by daily spatial variation in the
      monkeys' use of widespread foraging grids. In the forest height experiments, the
      two groups differed in their foraging responses, with 8% greater foraging overall
      for one group. However, forest height did not significantly impact foraging in
      either group, meaning that, given feeding opportunities, samango monkeys are able
      to utilise secondary growth forest. For one group, missed opportunity costs of
      staying with the group appeared through the statistical interaction of day with
      foraging location (the monkeys did not always spread out to take advantage of all
      available food patches). In several subsequent experiments in widespread grids,
      significant daily spatial variation in foraging occurred, pointing to spatial
      cohesion during group movement as likely being an important predictor of habitat
      use. For an individual social forager, staying with the group may be more
      important than habitat type in driving habitat selection.

PMID- 24432360
TI  - Depressive symptoms are associated with allostatic load among  community-dwelling
      older adults.
AB  - The allostatic load model has been used to quantify the physiological costs of
      the body's response to repeated stressful demands and may provide a useful,
      integrative perspective on the various correlates of late-life depressive
      symptoms. We interviewed 125 Rochester, NY adults, ranging in age from 67 to 94
      years. We employed an allostatic load score as a measure of multisystem
      dysfunction in hypothalamic-pituitary-adrenal axis function, immune function,
      anabolic activity, and cardiovascular activity. Overall, affective, and somatic
      depressive symptom scores were computed using the 20-item Center for
      Epidemiologic Studies Depression Scale. Multiple linear regression models were
      used to estimate associations between allostatic load scores and affective,
      somatic, and overall depressive symptoms. Among our sample of mean age 76.1
      years, the one-week prevalence of clinically significant depressive symptoms was
      12.8%. In models adjusting for demographic, socioeconomic, and health-related
      factors, higher allostatic load scores were associated with elevated scores for
      overall, affective, and somatic depressive symptoms: beta = 1.21 (95% CI = 0.38,
      2.05); beta = 0.14 (95% CI = 0.040, 0.24); beta = 0.60 (95% CI = 0.23, 0.97),
      respectively. Our results suggest that allostatic load measure is associated with
      late-life depressive symptoms. This association appears to be of clinical
      significance, as the magnitude of the effect size was comparable (but opposite in
      direction) to that of antidepressant use. Future research should examine the
      inter-relationships of allostatic load, psychological stress, and late-life
      depressive symptoms.

PMID- 24432362
TI  - Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases.
AB  - INTRODUCTION: Gout is a common arthritis that occurs particularly in patients who
      frequently have associated comorbidities that limit the use of conventional
      therapies. The main mechanism of crystal-induced inflammation is interleukin-1
      production by activation of the inflammasome. We aimed to evaluate the efficacy
      and tolerance of anakinra in gouty patients. METHODS: We conducted a multicenter
      retrospective review of patients receiving anakinra for gouty arthritis. We
      reviewed the response to treatment, adverse events and relapses. RESULTS: We
      examined data for 40 gouty patients (32 men; mean age 60.0 +/- 13.9 years)
      receiving anakinra. Mean disease duration was 8.7 +/- 8.7 years. All patients
      showed contraindications to and/or failure of at least two conventional
      therapies. Most (36; 90%) demonstrated good response to anakinra. Median pain on
      a 100-mm visual analog scale was rapidly decreased (73.5 (70.0 to 80.0) to 25.0
      (20.0 to 32.5) mm, P < 0.0001), as was median C-reactive protein (CRP) level
      (130.5 (55.8 to 238.8) to 16.0 (5.0 to 29.5) mg/l, P < 0.0001). After a median
      follow-up of 7.0 (2.0 to 13.0) months, relapse occurred in 13 patients after a
      median delay of 15.0 (10.0 to 70.0) days. Seven infectious events, mainly with
      long-term use of anakinra, were noted. CONCLUSIONS: Anakinra may be efficient in
      gouty arthritis, is relatively well tolerated with short-term use, and could be a
      relevant option in managing gouty arthritis when conventional therapies are
      ineffective or contraindicated. Its long-term use could be limited by infectious
      complications.

PMID- 24432363
TI  - Quantitative assessment of synovitis in patients with rheumatoid arthritis using
      fluorescence optical imaging.
AB  - INTRODUCTION: To prospectively evaluate quantitative assessment of fluorescence
      optical imaging (FOI) for differentiation of synovitic from non-synovitic joints
      in patients suffering from rheumatoid arthritis (RA). METHODS: FOI of the hands
      was performed in patients with active RA, and a stratified quantitative
      fluorescence readout (FLRO) of 3 phases (1-120 s; 121-240 s; 241-360 s) was
      generated for 5 individual joints of the clinical predominant hand (carpal joint,
      metacarpophalangeal and proximal interphalangeal joints of digits II & III). To
      dissect the effect of the overall perfusion of the hand from the perfusion due to
      synovitis, a fluorescence ratio (FLRA) was additionally calculated, dividing each
      FLRO by the readout of the eponychium of digit II. The mean FLRO and FLRA were
      compared between joints with absent vs. present synovitis determined by clinical
      examination, grayscale, color Doppler ultrasonography, or magnetic resonance
      imaging (MRI). RESULTS: The analysis for 90 individual joints from 18 patients
      yielded FLRO ranging from 4.4 to 49.0 * 10(3), and FLRAs ranging from 0.37 to
      2.27. Overall, the analyses based on the FLRA revealed a higher discrimination
      than the analyses related to the FLRO, demonstrating most significant differences
      in phases 2 and 3. A sensitivity of 26/39 (67%) and a specificity of 31/40 (77%)
      were calculated for FLRA of phase 3 using a cut-off value of more than 1.2 to
      detect MRI-confirmed synovitis with FOI. CONCLUSIONS: FOI has a potential for
      visualizing synovitis in subjects with RA. For adequate FOI interpretation,
      quantitative analysis should be based on the novel FLRA calculated for phases 2
      and 3.

PMID- 24432364
TI  - Effect of sclerostin-neutralising antibody on periarticular and systemic bone in
      a murine model of rheumatoid arthritis: a microCT study.
AB  - INTRODUCTION: Patients with chronic inflammatory diseases have increased bone
      loss and bone fragility and are at increased risk of fracture. Although anti
      resorptive drugs are effective in blocking inflammation-induced bone loss, they
      are less effective at rebuilding bone. We have previously shown that treatment
      with sclerostin antibody (Scl-AbI) builds bone and can prevent or restore bone
      loss in a murine model of inflammatory bowel disease. In this study, we tested
      the effect of Scl-AbI in a murine model of rheumatoid arthritis (the collagen
      induced arthritis model, CIA). We hypothesised that sclerostin blockade can
      protect and restore bone both locally and systemically without affecting
      progression of inflammation. METHODS: CIA was induced in male DBA/1 mice, which
      were treated with either PBS or Scl-AbI (10 mg/kg, weekly) prophylactically for
      55 days or therapeutically for 21 days (starting 14 days post onset of
      arthritis). Systemic inflammation was assessed by measuring the serum
      concentration of anti-CII IgG1, IgG2a and IgG2b by ELISA. Changes in bone mass
      and structure, either at sites remote from the joints or at periarticular sites,
      were measured using DEXA and microCT. Bone focal erosion was assessed in microCT
      scans of ankle and knee joints. RESULTS: Circulating anti-CII immunoglobulins
      were significantly elevated in mice with CIA and there were no significant
      differences in the levels of anti-CII immunoglobulins in mice treated with PBS or
      Scl-ABI. Prophylactic Scl-AbI treatment prevented the decrease in whole body bone
      mineral density (BMD) and in the bone volume fraction at axial (vertebral body)
      and appendicular (tibial proximal metaphysis trabecular and mid-diaphysis
      cortical bone) sites seen in PBS-treated CIA mice, but did not prevent the
      formation of focal bone erosions on the periarticular bone in the knee and ankle
      joints. In the therapeutic study, Scl-AbI restored BMD and bone volume fraction
      at all assessed sites but was unable to repair focal erosions. CONCLUSIONS:
      Sclerostin blockade prevented or reversed the decrease in axial and appendicular
      bone mass in the murine model of rheumatoid arthritis, but did not affect
      systemic inflammation and was unable to prevent or repair local focal erosion.

PMID- 24432365
TI  - Bone marrow lesion volume reduction is not associated with improvement of other
      periarticular bone measures: data from the Osteoarthritis Initiative.
AB  - INTRODUCTION: We evaluated the associations between bone marrow lesion (BML)
      volume change and changes in periarticular bone mineral density (paBMD) as well
      as subchondral sclerosis to determine whether BML change is associated with other
      local bone changes. METHODS: The convenience sample comprised participants in the
      Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee
      radiographs and magnetic resonance images (MRIs) at the 24- and 48-month visits
      and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month
      visits. The right knee was assessed unless contraindicated for MRI. We used knee
      DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L
      paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial
      tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a
      semiautomated segmentation method. To focus on knees with only medial tibia BML
      changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume
      change was classified into three groups: BML regression (lowest quartile of
      medial tibial BML volume change), no-to-minimal change (middle two quartiles),
      and BML progression (highest quartile). We used proportional odds logistic
      regression models to evaluate the association between quartiles of changes in
      medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change. RESULTS: The
      sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with
      radiographic osteoarthritis, and participants with a mean age of 63.8 +/- 9.3
      years and mean body mass index of 29.8 +/- 4.7 kg/m(2). We found an association
      between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95%
      confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression
      (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater
      increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML
      progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had
      borderline statistical significance. The frequency of sclerosis progression in
      the medial tibia (n = 14) was greater among knees with BML progression or
      regression compared with knees without BML change (P = 0.01 and P = 0.04,
      respectively). CONCLUSION: BML regression and BML progression are characterized
      by concurrent increases in paBMD and sclerosis, which are characteristic of
      increased radiographic osteoarthritis severity. At least during 24 months, BML
      regression is not representative of improvement in other periarticular bone
      measures.

PMID- 24432366
TI  - Poor knowledge of methotrexate associated with older age and limited English
      language proficiency in a diverse rheumatoid arthritis cohort.
AB  - INTRODUCTION: Our objective was to determine rheumatoid arthritis (RA) patients'
      understanding of methotrexate and assess whether knowledge varies by age,
      education, English language proficiency, or other disease-related factors.
      METHODS: Adults with RA (n = 135) who were enrollees of an observational cohort
      completed a structured telephone interview in their preferred language between
      August 2007 and July 2009. All subjects who reported taking methotrexate were
      asked 11 questions about the medication in addition to demographics, education
      level, and language proficiency. Primary outcome was a total score below the 50th
      percentile (considered inadequate methotrexate knowledge). Bivariable and
      multivariable logistic regressions were performed. Covariates included
      demographics, language proficiency, education, and disease characteristics.
      RESULTS: Of 135 subjects, 83% were female, with a mean age of 55 +/- 14 years.
      The majority spoke English (64%), followed by 22% Spanish and 14% Cantonese or
      Mandarin. Limited English language proficiency (LEP) was reported in 42%. Mean
      methotrexate knowledge score was 5.4 +/- 2.6 (range, 0 to 10); 73 (54%) had a
      score lower than 5 (of 10). Age older than 55, less than high school education,
      LEP, better function, and biologic use were independently associated with poor
      knowledge. CONCLUSIONS: In a diverse RA cohort, overall methotrexate knowledge
      was poor. Older age and limited proficiency in English were significant
      correlates of poor knowledge. Identification of language barriers and improved
      clinician-patient communication around methotrexate dosing and side effects may
      lead to improved safety and enhanced benefits of this commonly used RA
      medication.

PMID- 24432367
TI  - Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.)
      and identification of the active ingredient.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional medicine, Cynodon dactylon
      (Linn.) is used in asthma, but scientific studies to provide evidence for
      medicinal uses are sparse. Thus this study was undertaken to provide evidence for
      medicinal use in asthma as a bronchodilator, and to identify active
      ingredient(s). MATERIALS AND METHODS: In vivo, acetylcholine (Ach)-induced
      bronchospasm was conducted in guinea pig while isolated rat tracheal strip was
      suspended in organ bath to measure the concentration response curve using
      multichannel data acquisition system. RESULTS: The chloroform extract of Cynodon
      dactylon (CECD) protected against Ach-induced bronchospasm in guinea pigs,
      similar to atropine. In the in vitro studies, CECD relaxed carbachol (CCh) and
      high K+-induced contraction of rat tracheal strip, similar to atropine and
      verapamil respectively, suggesting antimuscarinic and calcium channel blocking
      (CCB) activities, which were confirmed by right ward shifting of CCh and Ca(+2)
      concentration response curve (CRC). The phosphodiestrase (PDE) inhibitory
      activity was confirmed by potentiation of isoprenaline-induced inhibitory
      response, similar to papaverine. Densitometry analyses led to the identification
      of scopoletin as an active ingredient. Effectively, it significantly inhibited
      high K+, and Ca(+2) induced contractile response, similar to verapamil. The
      phosphodiestrase (PDE) inhibitory activity was confirmed by direct evidence of
      potentiation of isoprenaline-induced inhibitory response, similar to papaverine.
      CONCLUSIONS: These results suggest that the bronchodilator activity of CECD is
      partly due to presence of scopoletin, and mediated possibly through CCB and PDE
      inhibition.

PMID- 24432368
TI  - Plants used for treatment of dysentery and diarrhoea by the Bhoxa community of
      district Dehradun, Uttarakhand, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dysentery and diarrhoea are major causes of
      morbidity and mortality in rural communities of developing world. The Bhoxa
      community is an important primitive indigenous community of Uttarakhand, India.
      In this paper we have tried to scientifically enumerate ethnomedicinal plants and
      herbal preparations used by Bhoxa community to treat dysentery and diarrhoea, and
      discuss their antidiarrhoeal properties in the light of previous ethnomedicinal,
      pharmacological, microbiological and phytochemical studies. To record plants and
      herbal preparations used by Bhoxa community of district Dehradun, Uttarakhand,
      India in treatment of dysentery and diarrhoea, and to discuss antidiarrhoeal and
      antimicrobial properties of the recorded plants. MATERIALS AND METHODS:
      Ethnomedicinal survey was conducted in different villages of Bhoxa community
      located in district Dehradun, Uttarakhand, India. Thirty Bhoxa traditional
      healers were interviewed to collect information on plants used by them for
      treating dysentery and diarrhoea. For each of the recorded plant species the use
      value (UV) and fidelity level (FL) was calculated. Detailed literature survey was
      conducted to summarize ethnomedicinal, pharmacological, microbiological and
      phytochemical information on the medicinal plants listed in the present study.
      RESULTS: Fifty medicinal plants (45 genera and 30 families) were used by Bhoxa
      community to treat dysentery and diarrhoea, among which 27 species were used for
      dysentery, 41 for diarrhoea and 18 for both dysentery and diarrhoea. Three plants
      viz., Dioscorea bulbifera L., Euphorbia thymifolia L. and Prunus persica (L.)
      Stokes, recorded in the present survey have been reported for the first time in
      treatment of dysentery and diarrhoea by any indigenous communities in India. FL
      and UV values revealed that most preferred species for the treatment of dysentery
      and diarrhoea by Bhoxa community are Euphorbia hirta L. followed by Holarrhena
      pubescens Wall., Helicteres isora L. and Cassia fistula L. Earlier
      pharmacological studies confirmed that 27 of the recorded plants have some proven
      antidiarrhoeal properties and remaining 23 plants have to be pharmacologically
      evaluated for their antidiarrhoeal properties. Except 6 plants all the other
      recorded plants have shown antimicrobial properties in previous microbiological
      studies. Previous studies have corroborated the ethnomedicinal claims made by the
      traditional healers of the Bhoxa community. CONCLUSIONS: Present study has
      provided new information on many medicinal plants and their uses. All the three
      newly reported plants for treatment of dysentery and diarrhoea have not been
      pharmacologically evaluated yet for their possible antidiarrhoeal properties.
      Twenty-three and six plants have not been evaluated pharmacologically and
      microbiologically, respectively. The present information may serve as a baseline
      data to initiate further research for discovery of new compounds and biological
      activities of these potential plants. Further research on these plants may
      provide some important clues for development of new drugs for dysentery and
      diarrhoea or other related diseases.

PMID- 24432369
TI  - Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-kB
      signaling pathway in isoproterenol-induced myocardial hypertrophy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV (As IV) is one of the main
      effective components isolated from the traditional Chinese medical herb
      Astragalus membranaceus. The protective effect of Astragalus membranaceus on
      myocardial hypertrophy has been extensively proved. To test the hypothesis that
      Astragaloside IV can ameliorate the myocardial hypertrophy and inflammatory
      effect induced by beta-adrenergic hyperactivity, we carried out in vivo and in
      vitro experiments. MATERIAL AND METHODS: In in vivo study, the isoproterenol
      (Iso) (5 mg kg(-1) d(-1)) was used as a model of myocardial hypertrophy by
      intraperitoneal injection. SD rats were randomly assigned to following six
      groups: A: the control; B: Iso group; C: Iso plus As IV 20 mg kg(-1) d(-1); D:
      Iso plus As IV 40 mg kg(-1) d(-1); E: Iso plus As IV 80 mg kg(-1) d(-1); F: Iso
      plus Propranolol 40 mg kg(-1) d(-1). In in vitro study, cultured neonatal rat
      cardiomyocytes were pretreated with As IV (3, 10, 30 MU mol L(-1)), Propranolol
      (2 MU mol L(-1)) and BAY11-7082 (5 MU mol L(-1)) for 30 min, and then incubated
      with Iso (10 MU mol L(-1)) for 48 h. For the rats in each group, the heart mass
      index (HMI) and the left ventricular mass index (LVMI) were measured. To measure
      the transverse diameter of left ventricular myocardial cells (TDM), the
      hematoxylin-eosin (HE) staining method was applied. In addition, the volume and
      the total protein content of cardiomyocytes were measured, the mRNA expression of
      ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4,
      IkappaBalpha and p65 were quantified by Western blot, and the level of TNF-alpha
      and IL-6 were measured by ELISA. RESULTS: In vivo: Comparing the Iso group to the
      control, the HMI, LVMI, TDM were significantly increased; the protein expression
      of TLR4 and p65 were increased, while the IkappaBalpha were decreased; the
      expression of ANP, TLR4 mRNA, and TNF-alpha, IL-6 in serum were significantly
      increased. These changes could be partly prevented by As IV and Pro. In vitro:
      the over-expression of the cell size, total protein content could remarkably down
      regulated by As IV and Pro, and the results of RT-PCR, Western blot and ELISA
      were similar to those of in vivo. CONCLUSIONS: The results of these studies
      indicate that Astragaloside IV has good protective effect on myocardial
      hypertrophy induced by isoproterenol. More specifically, the cardioprotection is
      related to inhibiting the TLR4/NF-kB signaling pathway and the attenuating
      inflammatory effect.

PMID- 24432370
TI  - Inhibition of arachidonic acid metabolism by the Andean crude drug Parastrephia
      lucida (Meyen) Cabrera.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Parastrephia lucida (Meyen) Cabrera is used in
      the traditional medicine of Argentinean highlands as an antiseptic and anti
      inflammatory medicinal plant. To give scientific support to the
      ethnopharmacological claim of Parastrephia lucida as an anti-inflammatory crude
      drug the effect of Parastrephia lucida extracts and fractions was assessed on key
      enzymes of the biosynthesis of pro-inflammatory eicosanoids mediators from
      arachidonic acid (AA). MATERIALS AND METHODS: A bio-guided fractionation of the
      plant extract was carried out to find out the compounds or mixtures responsible
      for the anti-inflammatory effect. The extracts and fractions were tested in vitro
      for their ability to inhibit the enzymes cyclooxygenase (COX)-1 and COX-2,
      lipoxygenase (LOX) and phospholipase (sPLA2). Fractions were analyzed by HPLC-MS,
      HPLC-ESI-MS/MS and NMR to relate the effect with groups of secondary metabolites.
      RESULTS: Parastrephia lucida was more effective inhibiting COX and sPLA2 than
      LOX. Assay-guided isolation led to the active fractions C and F which showed
      different effect on the selected enzymes. The fraction C was more effective
      inhibiting LOX while fraction F showed better activity against sPLA2 and COX-2.
      Both fractions were further worked-up following the isolation of the anti
      inflammatory agents with the selected enzyme assays. The main compounds
      identified in the most active fractions were 5,4'-dihydroxi-7-methoxyflavanone,
      apigenin, apigenin methyl ether and apigenin trimethyl ether, methyl and dimethyl
      ethers from quercetin, kaempferol and luteolin methyl ether, ferulic acid esters,
      cinnamic acid and vanillin. CONCLUSIONS: Parastrephia lucida extract inhibit AA
      metabolism via several enzymes. The results give support to the traditional use
      of this plant for the treatment of inflammatory disorders.

PMID- 24432371
TI  - The mechanism of the opening of the blood-brain barrier by borneol: a
      pharmacodynamics and pharmacokinetics combination study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Borneol is widely used in traditional Chinese
      medicine to facilitate the distribution of central nervous system (CNS) drugs in
      brain due to its ability to open blood-brain barrier (BBB), however, the
      underlying mechanism is still unclear. In this study, the effect of borneol on
      different brain regions were investigated to explore the mechanism. MATERIALS AND
      METHODS: After oral administration of borneol (0.1, 0.2 g/kg) for seven
      consecutive days, SD rats were injected with Rh123 (1.0 mg/kg). The
      concentrations of Rh123 were detected in four brain regions of cortex,
      hippocampus, hypothalamus and striatum by a small animal vivo imaging system and
      a fluorescence microplate reader respectively. The ultrastructures of BBB were
      examined. Moreover, the expressions of the four transporters of ATP-binding
      cassette (ABC) family, multidrug resistance 1a (Mdr1a), multidrug resistance 1b
      (Mdr1b), multidrug resistance protein 1 (Mrp1), Mrp4, Mrp5 and breast cancer
      resistance protein (Bcrp) in the four brain regions were analyzed. Finally, the
      deliveries of borneol in the plasma and the four brain regions were examined by a
      pharmacokinetics study. RESULTS: Administration of 0.2 g/kg borneol produced
      loose structure in the tight junction and void structure between the endothelial
      cell and mesangial cell. Borneol at 0.1 g/kg and 0.2 g/kg increased the delivery
      of Rh123 in hippocampus and hypothalamus obviously. Permeability index followed a
      similar trend. Protein expression assays showed that borneol decreased the
      expression of Mdr1 and Mrp1 in hippocampus and hypothalamus. Further RT-PCR study
      showed that borneol decreased the expressions of both Mdr1a and Mdr1b in
      hippocampus and hypothalamus. The pharmacokinetics study demonstrated that the
      delivery of borneol in cortex was the most and that in striatum the least, with
      the deliveries of borneol in hippocampus and hypothalamus in between.
      CONCLUSIONS: Borneol showed tissue specific BBB-opening effect, which was
      associated with its regulation of the ultrastructure of brain tissues and the
      expressions of Mdr1a, Mdr1b and Mrp1. The present study indicated that borneol
      should be used in concert with drugs targeting hippocampus or hypothalamus to
      exert its synergistic effect to the maximum.

PMID- 24432372
TI  - Importance of the methyl-citrate cycle on glycerol metabolism in the yeast
      Yarrowia lipolytica.
AB  - tA novel approach to trigger lipid accumulation and/or citrate production in vivo
      through the inactivation of the 2-methyl-citrate dehydratase in Yarrowia
      lipolytica was developed. In nitrogen-limited cultures with biodiesel-derived
      glycerol utilized as substrate, the phd1 mutant (JMY1203) produced 57.7 g/L of
      total citrate, 1.6-fold more than the wild-type strain, with a concomitant
      glycerol to citrate yield of 0.91 g/g.Storage lipid in cells increased at the
      early growth stages, suggesting that inactivation of the 2-methyl-citrate
      dehydratase would mimic nitrogen limitation. Thus, a trial of JMY1203 strain was
      performed with glycerol under nitrogen-excess conditions. Compared with the
      equivalent nitrogen-limited culture,significant quantities of lipid (up to ~ 31%
      w/w in dry weight, 1.6-fold higher than the nitrogen-limited experiment) were
      produced. Also, non-negligible quantities of citric acid (up to ~ 26 g/L, though
      0.57-fold lower than the nitrogen-limited experiment) were produced, despite
      remarkable nitrogen presence into the medium, indicating the construction of
      phenotype that constitutively accumulated lipid and secreted citrate in Y.
      lipolytica during growth on waste glycerol utilized as substrate.

PMID- 24432373
TI  - Aptamer modification improves the adenoviral transduction of malignant glioma
      cells.
AB  - Adenovirus has shown increasing promise in the gene-viral therapy for
      glioblastoma, a treatment strategy that relies on the delivery of viruses or
      transgenes into tumor cells. However, targeting of adenovirus to human
      glioblastoma remains a challenge due to the low expression level of coxsackie and
      adenovirus receptor (CAR) in glioma cells. Aptamers are small and highly
      structured single-stranded oligonucleotides that bind at high affinity to a
      target molecule, and are good candidates for targeted imaging and therapy. In
      this study, to construct an aptamer-modified Ad5, we first genetically modified
      the HVR5 of Ad hexon by biotin acceptor peptide (BAP), which would be
      metabolically biotinylated during production in HEK293 cells, and then attached
      the biotin labeled aptamer to the modified Ad through avidin-biotin binding. The
      aptamers used in this study includes AS1411 and GBI-10. The former is a DNA
      aptamer that can bind to nucleolin, a nuclear matrix protein found on the surface
      of cancer cells. The latter is a DNA aptamer that can recognize the extracellular
      matrix protein tenascin-C on the surface of human glioblastoma cells. To examine
      if aptamer-modification of the hexon protein could improve the adenoviral
      transduction efficiency, a glioblastoma cell line, U251, was transduced with
      aptamer-modified Ads. The transduction efficiency of AS1411- or GBI-10-modified
      Ad was approximately 4.1-fold or 5.2-fold higher than that of the control. The
      data indicated that aptamer modified adenovirus would be a useful tool for cancer
      gene therapy.

PMID- 24432374
TI  - Author reply: To PMID 23848217.

PMID- 24432375
TI  - Probucol inhibited Nox2 expression and attenuated podocyte injury in type 2
      diabetic nephropathy of db/db mice.
AB  - The present study was conducted to investigate the effects of probucol on the
      progression of diabetic nephropathy and the underlying mechanism in type 2
      diabetic db/db mice. Eight weeks db/db mice were treated with regular diet or
      probucol-containing diet (1%) for 12 weeks. Non-diabetic db/m mice were used as
      controls. We examined body weight, blood glucose, and urinary albumin. At 20
      weeks, experimental mice were sacrificed and their blood and kidneys were
      extracted for the analysis of blood chemistry, kidney histology, oxidative stress
      marker, and podocyte marker. As a result, 24 h urinary albumin excretions were
      reduced after probucol treatment. There were improvements of extracellular matrix
      accumulation and fibronectin and collagen IV deposition in glomeruli in the
      probucol-treated db/db mice. The reduction of nephrin and the loss of podocytes
      were effectively prevented by probucol in db/db mice. Furthermore, probucol
      significantly decreased the production of thiobarbituric acid-reactive substances
      (TBARS), an index of reactive oxygen species (ROS) generation and down-regulated
      the expression of Nox2. Taken together, our findings support that probucol may
      have the potential to protect against type 2 diabetic nephropathy via
      amelioration of podocyte injury and reduction of oxidative stress.

PMID- 24432376
TI  - Biofunctionalization of cellulosic fibres with L-cysteine: assessment of
      antibacterial properties and mechanism of action against Staphylococcus aureus
      and Klebsiella pneumoniae.
AB  - The main purpose of this work is to obtain a cotton-based textile material
      functionalized with L-cysteine (L-cys) to achieve an antimicrobial effect with
      potential application in biomedical, geriatric or pediatric textiles. The binding
      capacity of L-cys to cotton fibres was assessed through different
      functionalization strategies--surface activation and exhaustion processes. A
      subsequent analysis of the possible antibacterial action against Staphylococcus
      aureus and Klebsiella pneumoniae was performed according with the Japanese
      International standard (JISL, 2008). To determine the mechanism of action of L
      cys on the selected strains, flow cytometry was used. The results revealed that
      the exhaustion process was performed with success to confer bioactivity to the
      treated fabric, as assessed by an effective antibacterial effect against both
      Gram-positive and Gram-negative bacteria, and successfully linkage of L-cys was
      observed via FTIR with a durable effect demonstrated after the washing tests
      (fastness to washing). It was also observed that L-cys exerts a bacteriostatic
      effect against both bacterial strains, since there were alterations in the
      metabolic activity of the microorganisms after the application of the bioactive
      textile which was shown by the CTC (cyanoditolyl tetrazolium chloride) staining
      used in flow cytometry. This study shows a new and successful biotechnological
      process to develop antibacterial textiles through the functionalization of cotton
      fibres with L-cys which presents a broad range of applications in healthcare,
      since L-cys is a natural antibacterial compound, non-toxic and affects pathogenic
      bacteria related to hospital infections.

PMID- 24432377
TI  - The development of ternary nanoplexes for efficient small interfering RNA
      delivery.
AB  - Targeted posttranscriptional gene silencing by RNA interference (RNAi) has
      garnered considerable interest as an attractive new class of drugs for several
      diseases, such as cancer. Chitosan and protamine are commonly used as a vehicle
      to deliver and protect small interfering RNA (siRNA), but the strong interaction
      still remains to be modulated for efficient siRNA uptake and silencing.
      Therefore, in this study, ternary nanoplexes containing chitosan and protamine
      were designed to substantially enhance the siRNA efficiency. Binary and ternary
      nanoplexes were prepared at different the ratios of moles of the amine groups of
      cationic polymers to those of the phosphate ones of siRNA (N/P) ratios and
      characterized in terms of size, zeta potential, morphology and serum stability.
      The silencing efficiencies and cytotoxicities of prepared nanoplexes were
      evaluated by enzyme-linked immunosorbent assay (ELISA) (for human vascular
      endothelial growth factor; hVEGF) and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays, respectively. The mean diameter of
      ternary nanoplexes ranged from 151 to 282 nm, depending on the weight ratio
      between polymers and siRNA. The gene silencing effect after transfection with
      ternary nanoplexes (chitosan/siRNA/protamine 83%) was significantly higher than
      that with binary nanoplexes (chitosan/siRNA 71% and protamine/siRNA 74%). Ternary
      nanoplexes showed the highest cellular uptake ability when compared with binary
      nanoplexes. Ternary nanoplexes did not induce substantial cytotoxicity. Serum
      stability and the lack of cytotoxicity of the nanoplexes provided advantages over
      other gene silencing studies. These results suggest ternary nanoplexes have the
      potential to be an effective siRNA carrier to study the gene silencing effect.

PMID- 24432378
TI  - Inhibition of nitric oxide and tumour necrosis factor-alpha production in
      peritoneal macrophages by Aspergillus nidulans melanin.
AB  - The naturally occurring pigment, melanin is found in organisms of all
      phylogenetic kingdoms, including fungi, and exhibits a wide range of biological
      activities. Our objective was to investigate the effects of melanin extracted
      from the fungus Aspergillus nidulans on the production of the pro-inflammatory
      mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) in
      peritoneal macrophages and on the viability of McCoy mouse fibroblasts. The
      results showed that A. nidulans melanin did not stimulate NO production in
      macrophages, but it inhibited the NO production in lipopolysaccharide (LPS)
      stimulated macrophages by approximately 82%. Similarly, A. nidulans melanin
      inhibited LPS-stimulated TNF-alpha production by 52% and showed a slight
      stimulatory effect on TNF-alpha production in macrophages. In addition, the
      toxicity of A. nidulans melanin to McCoy cells was much lesser (IC50=373.5+/-2.4
      ug/mL) than that of known agents such as cisplatin (IC50=41.2 ug/mL). The
      viability of peritoneal macrophages was greater than 90% at the highest melanin
      concentration tested (100 ug/mL). Thus, the combination of low cytotoxicity and
      marked inhibition of TNF-alpha and NO production suggests that A. nidulans
      melanin has potential as an anti-inflammatory agent and may be used in the future
      for development of new drugs with therapeutic utility.

PMID- 24432379
TI  - Synergistic antitumor activities of sepantronium bromide (YM155), a survivin
      suppressant, in combination with microtubule-targeting agents in triple-negative
      breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) has a poor prognosis compared to other
      subtypes, and effective treatment options are limited to cytotoxic agents,
      including microtubule-targeting agents, due to the lack of molecular targets.
      Here, we examined the combined effect of sepantronium bromide (YM155) and
      microtubule-targeting agents in TNBC models. The combination of YM155 with
      docetaxel showed synergistic antiproliferative and caspase 3/7-inducing effects
      in MRK-nu-1 and MDA-MB-453 human TNBC cell lines in vitro. YM155 also
      synergistically enhanced the efficacies of other microtubule-targeting agents,
      including paclitaxel and vinorelbine, which induced accumulation of survivin at
      the G2/M phase, whereas it did not affect the efficacy of doxorubicin.
      Combination treatment with YM155 and microtubule-targeting agents decreased the
      accumulation of survivin at the G2/M phase and induced greater apoptosis than
      either single agent alone. Further, combination treatment with YM155 and
      docetaxel also had a synergistic antitumor effect, achieving complete regression
      without exacerbation of body weight loss in all mice, in a MRK-nu-1 human TNBC
      xenograft model. These results suggest that survivin inhibition synergistically
      sensitize human TNBC cells to microtubule-targeting agents.

PMID- 24432380
TI  - Osthole reverses beta-amyloid peptide cytotoxicity on neural cells by enhancing
      cyclic AMP response element-binding protein phosphorylation.
AB  - Accumulation of beta-amyloid peptide (Abeta) in the brain plays an important role
      in the pathogenesis of Alzheimer's disease (AD). Previous studies have
      demonstrated the neuroprotective role of osthole against oxygen and glucose
      deprivation in cortical neurons. However, the effects of osthole on Abeta-induced
      neurotoxicity in neural cells have rarely been reported. The current study was
      designed to investigate the protective effects of osthole on a cell model of AD
      insulted by exogenous Abeta25-35 and the potential mechanism(s). In this study, 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,
      immunofluorescence analysis, apoptosis assay, reverse transcription polymerase
      chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) techniques
      were used in primary cortical neurons and SH-SY5Y cells. Our data showed that
      osthole reduced intracellular Abeta levels in neural cells, which was associated
      with decreased BACE1 protein; osthole reversed exogenous Abeta25-35-induced cell
      viability loss, apoptosis, and synapsin-1 reduction, which was related to the
      reestablishment of phosphorylation of cyclic AMP response element-binding protein
      (CREB). The collective evidence indicates that osthole possesses the ability to
      protect cortical neurons and SH-SY5Y cells against Abeta injury, and the
      underlying mechanism may be attributed to the enhancement of CREB
      phosphorylation.

PMID- 24432381
TI  - Large-scale production of functional human lysozyme in transgenic cloned goats.
AB  - Human lysozyme (hLZ), an essential protein against many types of microorganisms,
      has been expressed in transgenic livestock to improve their health status and
      milk quality. However, the large-scale production of hLZ in transgenic livestock
      is currently unavailable. Here we describe the generation of transgenic goats, by
      somatic cell-mediated transgenic cloning, that express large amounts of
      recombinant human lysozyme (rhLZ) in milk. Specifically, two optimized lysozyme
      expression cassettes (beta-casein/hLZ and beta-lactoglobulin/hLZ) were designed
      and introduced into goat somatic cells by cell transfection. Using transgenic
      cell colonies, which were screened by 0.8 mg/mL G418, as a nuclear donor, we
      obtained 10 transgenic cloned goats containing one copy of hLZ hybrid gene. An
      ELISA assay indicated that the transgenic goats secreted up to 6.2 g/L of rhLZ in
      their milk during the natural lactation period, which is approximately 5-10 times
      higher than human milk. The average rhLZ expression levels in beta-casein/hLZ and
      beta-lactoglobulin/hLZ transgenic goats were 2.3 g/L and 3.6 g/L, respectively.
      Therefore, both rhLZ expression cassettes could induce high levels of expression
      of the rhLZ in goat mammary glands. In addition, the rhLZ purified from goat milk
      has similar physicochemical properties as the natural human lysozyme, including
      the molecular mass, N-terminal sequence, lytic activity, and thermal and pH
      stability. An antibacterial analysis revealed that rhLZ and hLZ were equally
      effective in two bacterial inhibition experiments using Staphylococcus aureus and
      Escherichia coli. Taken together, our experiments not only underlined that the
      large-scale production of biologically active rhLZ in animal mammary gland is
      realistic, but also demonstrated that rhLZ purified from goat milk will be
      potentially useful in biopharmaceuticals.

PMID- 24432382
TI  - Use of the psbA-trnH region to authenticate medicinal species of Fabaceae.
AB  - Fabaceae is a huge family that contains a large number of medicinal plants, many
      of which are commonly used in Chinese traditional medicine. However, traditional
      taxonomy has not been able to meet the complicated demands of species
      discrimination within Fabaceae. Thus, we employed a famous DNA barcode, the psbA
      trnH region, to discriminate commonly used medicinal species of the family
      Fabaceae. Here, the psbA-trnH regions derived from 152 samples were amplified.
      These samples represented 104 Fabaceae medicinal species from 60 genera,
      including 25 authentic Fabaceae species listed in the Chinese pharmacopoeia and
      common adulterant species. The results indicate that the psbA-trnH region
      performed well in terms of its universality and high variability in length and
      composition. Species discriminative power analysis of the psbA-trnH region showed
      that 91.3% of species could be identified successfully by the BLAST1 method in
      conjunction with the nearest distance method. And, the species resolution rate of
      the TaxonGap method exceeded 93%. The results provide support for the use of the
      psbA-trnH plastid region as a sensitive marker to the authentication of Fabaceae
      medicinal plants.

PMID- 24432383
TI  - Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury
      via suppression of oxidative stress and Kupffer cell activation.
AB  - This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC)
      on chronic ethanol-induced hepatic injury. Rats underwent intragastric
      administration of ethanol (5.0-9.0 g/kg) once a day for 12 weeks. A subset of
      rats were also intragastrically treated with AAPC (2, 4 or 8 mg/kg) once a day.
      In the end, AAPC treatment significantly protected against ethanol-induced liver
      injury, as evidenced by the decrease in serum alanine and aspartate
      aminotransferases levels and the attenuation of histopathological changes in
      rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde
      concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase
      activities. Mechanistically, studies showed that AAPC remarkably alleviated the
      formations of malondialdehyde and myeloperoxidase, restored impaired
      antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione
      reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity.
      Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up
      regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88
      (MyD88) as well as nuclear factor-kappaB were also suppressed by AAPC in ethanol
      intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced
      hepatotoxicity was mainly due to its ability to attenuate oxidative stress and
      inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and
      the expression of TLR4, CD14 and MyD88.

PMID- 24432384
TI  - Tissue transglutaminase: an emerging target for therapy and imaging.
AB  - Tissue transglutaminase (transglutaminase 2) is a multifunctional enzyme with
      many interesting properties resulting in versatile roles in both physiology and
      pathophysiology. Herein, the particular involvement of the enzyme in human
      diseases will be outlined with special emphasis on its role in cancer and in
      tissue interactions with biomaterials. Despite recent progress in unraveling the
      different cellular functions of transglutaminase 2, several questions remain.
      Transglutaminase 2 features in both confirmed and some still ambiguous roles
      within pathological conditions, raising interest in developing inhibitors and
      imaging probes which target this enzyme. One important prerequisite for
      identifying and characterizing such molecular tools are reliable assay methods to
      measure the enzymatic activity. This digest Letter will provide clarification
      about the various assay methods described to date, accompanied by a discussion of
      recent progress in the development of inhibitors and imaging probes targeting
      transglutaminase 2.

PMID- 24432385
TI  - Sulfur incorporation generally improves Ricin inhibition in pterin-appended
      glycine-phenylalanine dipeptide mimics.
AB  - Several 7-aminoamido-pterins were synthesized to evaluate the electronic and
      biochemical subtleties observed in the 'linker space' when N-{N-(pterin-7
      yl)carbonylglycyl}-l-phenylalanine 1 was bound to the active site of RTA. The
      gylcine-phenylalanine dipeptide analogs included both amides and thioamides.
      Decarboxy gly-phe analog 2 showed a 6.4-fold decrease in potency (IC50 = 128
      MUM), yet the analogous thioamide 7 recovered the lost activity and performed
      similarly to the parent inhibitor (IC50 = 29 MUM). Thiourea 12 exhibited an IC50
      nearly six times lower than the oxo analog 13. All inhibitors showed the pterin
      head-group firmly bound in their X-ray structures yet the pendants were not fully
      resolved suggesting that all pendants are not firmly bound in the RTA linker
      space. Calculated log P values do not correlate to the increase in bioactivity
      suggesting other factors dominate.

PMID- 24432386
TI  - Synthesis of 2'-O-(thymin-1-yl)methyluridine and its incorporation into secondary
      nucleic acid structures.
AB  - A double-headed nucleoside wherein an additional thymine is attached to the 2'-O
      position of uridine via a methylene linker is prepared and incorporated into
      oligonucleotides. With single incorporations of the modified nucleotide monomer,
      these oligonucleotides form duplexes with the complementary DNA sequences which
      are thermally less stable as compared to the unmodified duplexes. However,
      stabilization of bulged duplexes or three way junctions is observed. A cross
      strand interaction between two additional thymines is also seen in a DNA-duplex,
      when specifically introduced in a so-called (+1)-zipper motif, however, much
      weaker than obtained with the corresponding analogue with the methylene linker
      directly attached to the 2'-C-position. This demonstrates that the ability to act
      as a compressed dinucleotide is unique for the latter and due to its perfect
      preorganization of the additional base in the duplex core.

PMID- 24432387
TI  - Looking back and looking forward: celebrating 20 years of the Cochrane
      Collaboration and celebrating release of exciting evidence based approaches to
      decreasing antipsychotic use in long-term care.

PMID- 24432388
TI  - [Acetabulum fracture: precise percutaneous screw fixation by better imaging].

PMID- 24432389
TI  - [Craniocerebral trauma, visualizing damage after mild traumatic brain injury].

PMID- 24432390
TI  - Response.

PMID- 24432391
TI  - [Virtual colonoscopy: CT colonography for primary diagnosis of colon cancer
      symptoms].

PMID- 24432392
TI  - Response.

PMID- 24432393
TI  - [Pancreatic cancer: usefulness of CT after neoadjuvant therapy].

PMID- 24432394
TI  - [Coronary heart disease: CT angiography with blood flow analysis as an
      alternative to invasive coronary angiography].

PMID- 24432395
TI  - Response.

PMID- 24432396
TI  - [Migraine: Structural brain changes in MRI].

PMID- 24432397
TI  - [Congenital diaphragmatic hernia: Prenatal liver-thorax volume ratio as a marker
      for postnatal survival].

PMID- 24432398
TI  - Response.

PMID- 24432399
TI  - [Diagnosis of hepatic fibrosis: Diffusion-weighted MRI is unsuitable].

PMID- 24432400
TI  - Flu vaccination: get it.

PMID- 24432401
TI  - [Prostate cancer staging: 1 1 C-Acetat-PET/CT as a sensitive marker for nodal
      metastases].

PMID- 24432402
TI  - [Gadolinium-containing contrast agents: Gadoterat-meglumine is safe in patients
      with chronic renal failure].

PMID- 24432403
TI  - [Esophageal carcinoma: correlation between tumor avidity and lymph node
      metastasis].

PMID- 24432404
TI  - [Reply to letter to the editor].

PMID- 24432406
TI  - The threat of antibiotic resistance.

PMID- 24432405
TI  - A renal metanephric adenoma showing both a 2p16e24 deletion and BRAF V600E
      mutation: a synergistic role for a tumor suppressor gene on chromosome 2p and
      BRAF activation?
AB  - Metanephric adenomas (MAs) are rare benign tumors that may be difficult to
      recognize. Specific genetic anomalies might aid in diagnosis, but genomic data
      are limited and conflicting. Consistent mutations of the BRAF gene have been
      recently reported in MAs and could become useful as a discriminative marker among
      renal tumors. We report here a case of MA, showing both a BRAF V600E mutation and
      a segmental loss within bands 2p16 and 2p24 as the sole quantitative genomic
      anomaly. We compared the borders and size of the deleted region in our case to
      those of five cases of MAs previously reported. We identified a common minimal
      region containing 87 genes, among which several tumor suppressor genes could be
      candidate actors in the pathogenesis of MA. We ruled out MSH2 and MSH6 as target
      gene candidates, both located in the deleted region, on the basis of preserved
      expression and microsatellite sequence stability. Our study confirms the
      recurrence of a BRAF mutation and of 2p alterations in MAs. This first case
      showing simultaneous presence of a BRAF mutation and a 2p deletion raises the
      question of a synergistic role for these two anomalies in the pathogenesis of
      MAs.

PMID- 24432407
TI  - Identification and pharmacological characterization of the histamine H3 receptor
      in cultured rat astrocytes.
AB  - Recently we reported that cultured rat cortical astrocytes express histamine H3
      receptor that is functionally coupled to Gi/o proteins and participates to the
      stimulatory effect of histamine. Due to the lack of data on the distribution of
      histamine H3 receptors on glial cells we further investigated their presence in
      cultured astrocytes from different brain regions. Real-time PCR was performed to
      examine the expression of native histamine H3 receptor in cultured rat astrocytes
      from cortex,cerebellum, hippocampus and striatum.Double-antigen
      immunofluorescence staining and[3H]N-alpha-methylhistamine([3H]NalphaMH) binding
      studies were utilized to specifically identify and characterize receptor binding
      sites in astrocytes. Histamine H3 receptor mRNA was detected in rat astrocytes
      from all the regions under investigation with the highest levels in striatal
      astrocytes followed by hippocampal astrocytes and approximately equal levels in
      cerebellar and cortical astrocytes.Double-antigen immunofluorescence confirmed
      the presence of histamine H3 receptors on the membrane of all examined astroglial
      populations.[3H]NalphaMH bound with high affinity and specificity to an
      apparently single class of saturable sites on cortical astrocytic
      membranes(KD1/44.5570.46 nM; Bmax1/45.6370.21 fmol/mg protein)and competition
      assays with selective agonists and antagonists were consistent with labeling of
      histamine H3 receptor(range of pKi values 7.50-8.87). Our study confirmed the
      ability of cultured astrocytes from different rat brain regions to express
      histamine H3 receptors.The observed diverse distribution of the receptors within
      various astrocytic populations possibly mirrors their heterogeneity in the brain
      and indicates their active involvement in histamine-mediated effects.

PMID- 24432409
TI  - The attraction of Magnet.

PMID- 24432408
TI  - Oxidative stress induced by tert-butylhydroperoxide interferes with the placental
      transport of glucose: in vitro studies with BeWo cells.
AB  - Increased oxidative stress is implicated in the onset and progression of
      prevalent pregnancy disorders (e.g. gestational diabetes and fetal growth
      restriction),and in programming the fetus to develop metabolic diseases later in
      life.Since the molecular mechanisms underlying these effects of oxidative stress
      are largely unexplored, we aimed to investigate if the placental transport of
      glucose - the main energetic substrate for the fetus and placenta - is altered by
      oxidative stress.In a human syncytiotrophoblast (STB)cell model, the BeWo cell
      line,oxidative stress was induced by treatment with 100 mM tert
      butylhydroperoxide(tert-BOOH) for 24 h. Tert-BOOH decreased the steady-state
      intracellular accumulation (Amax) of[3H]2-deoxyglucose([3H]DG) mediated by both
      facilitative(GLUT) and non-facilitative(non-GLUT)glucose transporters.These
      effects were not associated with a change in the mRNA expression level of GLUT1,
      the major placental glucose transporter. Also,they seemed to be independent from
      phosphoinositide 3-kinase and protein kinase C signaling pathways and were
      unchanged either by inhibitors of free radical-generating enzymes or by free
      radical scavengers. In contrast, the dietary polyphenols quercetin,
      epigallocatechin-3-gallate and resveratrol completely reversed the inhibitory
      effect of tert-BOOH upon[3H]DG accumulation through a specific effect on GLUT
      mediated transport. Finally, tert-BOOH induced an increase in the transepithelial
      permeability to [3H]DG in the apical-to-basal direction, apparently related to an
      increase in its paracellular transport. In conclusion, tert-BOOH-induced
      oxidative stress reduces STB accumulation of glucose associated with an increase
      in its transepithelial permeability. This effect may contribute to the
      deleterious consequences of pregnancy disorders associated with oxidative stress.

PMID- 24432410
TI  - Is era of patient-reported outcomes at hand?

PMID- 24432411
TI  - Do you need to do an RCA on your RCA?

PMID- 24432413
TI  - Report: cancer care could use a makeover.

PMID- 24432412
TI  - A little this and a little that equals success.

PMID- 24432414
TI  - Collaborating with families and children.

PMID- 24432415
TI  - Are new nurses 'too posh to wash.

PMID- 24432416
TI  - Aged care offers great experience.

PMID- 24432417
TI  - Work is my home, says dedicated caregiver.

PMID- 24432418
TI  - What are the requirements for hospices to have "branch" offices?

PMID- 24432419
TI  - [Forensic histological assessment of brain contusion in the elderly subjects
      suffering from arterial hypertension].
AB  - This article reports an original observation of a few cases of brain injury in
      subjects presenting with elevated blood pressure. The standard histological
      staining techniques and immunohistological method were used to detect GFAP in
      astrocytes. The morphological features of this type of brain injury in the
      elderly subjects are described, the possibility of using them for the analysis of
      the damage is considered.

PMID- 24432420
TI  - [On the method of forensic medical examination of the injuries inflicted and
      traces left by the objects having the rubber surface].
AB  - A method of forensic medical examination of the injuries inflicted and traces
      left by the objects having the rubber surface is proposed. The method permits to
      reveal the facts of contact of injurious rubber things with biological and non
      biological objects. Its application extends the possibilities for determining the
      direction of movement and the weight of a vehicle running over the body of the
      victim.

PMID- 24432421
TI  - [Characteristics of the injuries inflicted by high-energy bullets from pneumatic
      air weapons].
AB  - The author compares the properties (caliber, power, speed) of the firearm
      projectiles and bullets with the high muzzle energy shot from pneumatic weapons.
      Results of experimental observations with the use of biological and non
      biological objects are presented. The entry and exit wounds in the skin and bones
      as well as the resulting damage inflicted to the tissues and the character of
      bullet deformation are described.

PMID- 24432422
TI  - [Morphological characteristics of stab and slush injuries to the skin inflicted
      by the ragged-spine knife].
AB  - The objective of the present study was to identify morphological features of stab
      and slush injuries to the skin inflicted with the ragged-spine knife. Visual and
      stereoscopic examination of experimental skin injuries to the biodummies revealed
      a number of peculiar characteristics of such wounds. Their severity is shown to
      depend on such factors as pressure on the spine or the blade.

PMID- 24432423
TI  - [Multilocus genotyping of polymorphous STR-loci of chromosomal DNA in individual
      cells: technical difficulties].
AB  - This study was designed to estimate the effectiveness of special technical
      procedures for the enhancement of sensitivity of multiplex analysis of DNA, such
      as the use of low-plexity PCR systems and the whole genome preamplification
      technology, and the possibility of their application for the purpose of forensic
      medical genotyping of polymorphous STR-loci of chromosomal DNA in individual
      cells. The authors refused to use the imitation model (equivalent DNA dilutions)
      for the sake of obtaining the maximally informative data and chose to work with
      real preparations of solitary buccal epithelial cells isolated by the laser
      microdissection technique. It was shown that neither the use of the low-plexity
      multilocus PCR systems nor the whole genome pre-amplification technology makes
      possible reliable genotyping of STR-loci of chromosomal DNA in individual cells.
      The proposed techniques allow for DNA genotyping in preparations consisting of 10
      diploid cells whereas the methods for reliable genotyping of STR-loci of
      chromosomal DNA in individual cells remains to be developed.

PMID- 24432424
TI  - [The vermillion border of the lips as the object of medico-criminalistics
      expertise].
AB  - The objective of the present work was to study biometric characteristics of the
      vermillion border of the lips and estimate the possibility of their use for
      personality identification. Photographs of the lips obtained from the archive of
      the Department of Forensic Medical Personality Identification, Russian Centre of
      Forensic Medical Expertise, were analysed with the use of the specially developed
      ALips 2.0 software. Verification of the hypothesis of normal sign distribution
      allowed the values of the signs to be split into intervals. Category limits of
      each sign were calculated for both men and women, the categories were compared in
      the automatic regime with the help of the ALips 2.0 software. The diagnostic
      value of the described system is thus far rather low. A number of calculation
      procedures allowing to identify the object of interest were performed at the
      concluding stage of the study. The results of experiments suggest the high
      identification significance of the signs under consideration while the number of
      the objects similar to the one being identified does not exceed five which
      confirms that the groups are fairly well distinguished.

PMID- 24432425
TI  - [The study of naphthyzin present in material evidence and biological fluids].
AB  - The optimal conditions for isolation of naphazoline from naphthyzin preparations
      and biological fluids with chloroform at pH 9.18 are described. The compound of
      interest was identified with the use of color and precipitation reactions, IR and
      UV spectroscopy, thin-layer and gas chromatography, and chemical methods
      including high performance liquid chromatography, chromatodensitometry, and UV
      spectroscopy. The results obtained by the three methods are comparable.

PMID- 24432426
TI  - [Peculiarities of the bancol distribution in the organism of the warm-blooded
      animals].
AB  - The distribution of bancol in the organism of the warm-blooded animals was
      studied following a single intragastric administration of this poisonous agent to
      the rats in the form of aqueous suspension at a dose equivalent to double LD50.
      It was shown that the largest amounts of bancol were accumulated in the stomach
      contents, heart, and spleen.

PMID- 24432427
TI  - [Analysis of the structure of publications on toxicological (forensic) chemistry
      in the journal "Problemy ekspertizy v meditsine (Problems of Expertise in
      Medicine)" for 2001-2009].

PMID- 24432428
TI  - [On the quality control in forensic biochemical departments].
AB  - The main principles of quality control in the laboratory practice of forensic
      biochemical departments are discussed. Recommendations on international
      standardization are suggested. Characteristics of the main phases of
      intralaboratory quality control of investigations and the reagents used in them
      are described. The necessity of quality control at all stages of forensic
      biochemical studies and expertise is emphasized.

PMID- 24432429
TI  - [A case of the long-term presence of a gauze pad in the abdominal cavity].

PMID- 24432430
TI  - [About eligibility of certificates of death from hepatic insufficiency].
AB  - Death from hepatic insufficiency is casuistic and occurs only in rare cases of
      fulminant viral hepatitis B, poisoning with some hepatotrophic compounds, and
      reaction to certain pharmaceutical products. Hepatic insufficiency is frequently
      indicated as the immediate cause of death of the subjects suffering liver
      cirrhosis and some other diseases in postmortem conclusions of forensic medical
      expertise and autopsy protocols. This mistake ensues from the incorrect
      interpretation of the results of laboratory analysis of the affected hepatocytes
      as manifestations of compromised liver function. The true cause of death to be
      stated in death certificates should be deduced based on different
      characteristics.

PMID- 24432431
TI  - [The legal frameworks and organizational forms of the work of a forensic medical
      expert participating in group investigation activities].
AB  - The problems pertaining to the modern organization of group investigation
      activities and the role of a forensic medical expert involved in them are
      discussed. It is shown that the variety of such groups formed in accordance with
      departmental and interdepartmental guidelines and regulations can be reduced to
      two major types, viz. investigation teams (brigades) and alert operational
      investigations groups. Either type can and some must include a forensic medical
      expert although neither legal nor institutional frameworks has been formulated
      for his participation.

PMID- 24432432
TI  - [The teaching and guiding forensic medical commission: its significance role in
      the educational process].
AB  - The activities of the Educational and Methodological Association (EMA) for
      pharmaceutical teaching in the Russian higher education institutions were renewed
      and updated. The Educational and Methodological Commission (EMC) on forensic
      medicine is an integral part of EMA. EMC was set up with an object of further
      developing the system of continuous professional education, implementing the
      federal state educational standard of the third generation, preserving and
      maintaing the uniform educational environment. The work of EMC in the field of
      forensic medicine is of primary importance for the optimization of academic
      activities in medical higher education institutions and research institutes
      training personnel for forensic medical facilities.

PMID- 24432433
TI  - [Forensic medicine as the cradle of toxicology in Russia].
AB  - Modern toxicology as a science and educational subject originated from forensic
      medicine in the middle of the XIXth century. In the beginning, selected
      toxicological problems were taught in the Emperor's Medical Surgical Academy
      (presently S.M. Kirov Military Medical Academy, Sankt-Peterburg) and at the
      Medical Faculty of the Moscow University (presently I.M. Sechenov First Moscow
      State Medical University, Moscow). The greatest contribution to the development
      of toxicology was made by such outstanding scientists as professors S.A. Gromov,
      P.P. Pelekhin, P.P. Zablotsky-Desyatovsky, E.V. Pelikan, Ya.A. Chistovich, G.I.
      Blosfel'd, I.M. Sorokin, D.P. Kosorotov, A.V. Grigoriev, V.V. Andreev, A.A.
      Glebovich, A.N. Grigoriev, B.I. Predtechensky, V.M. Rozhkov, S.S. Vail, M.N.
      Lubotsky, etc. The works of these researchers predetermined the further
      development of toxicology in this country, its main purpose being provision of
      medical aid in case of poisoning and diseases of chemical etiology. Another line
      of toxicological research became industrial and environmental toxicology having
      the purpose of hygienic rating and prevention of poisoning. Nevertheless, all
      aspects of the multifaceted science of toxicology are related to forensic
      medicine as the cradle in which it originated, evolved, and turned into a self
      consistent science.

PMID- 24432434
TI  - [Professor Adelaida Petrovna Zagryadskaya (on the occasion of her 90th birthday
      anniversary)].

PMID- 24432439
TI  - The top 5 test you probably don't need.  Some health screenings may do more harm
      than good.

PMID- 24432440
TI  - Ask the doctor.  It seems like more and more people are wearing various devices
      that measure how active they are.  Is this really valuable, or is it just a fad?

PMID- 24432441
TI  - Ask the doctor.  I hear that stress causes our cells to age faster.  Is there
      something to this, or is it just more nonsense to worry about?

PMID- 24432442
TI  - The glaucoma you may be missing.  Sometimes normal eye pressures mask the
      condition.

PMID- 24432443
TI  - Depression: is it just a slump or something more?  It's important for both your
      physical and emotional well-being to get help as soon as you suspect it.

PMID- 24432444
TI  - Could your joint pain be bursitis?  The tip-off may be swelling near, but not in,
      the joints.

PMID- 24432445
TI  - Getting your protein from plants.  It's an easy way to increase your fiber,
      vitamins, and minerals.

PMID- 24432446
TI  - Get to know your food labels.  You can ignore the carb counts, but pay strict
      attention to serving size, calories, and fat types.

PMID- 24432447
TI  - Bad mix: blood thinners and NSAIDs.  Take the lowest dose of NSAIDs and stop
      using them as soon as possible.

PMID- 24432448
TI  - Skipping breakfast hurts heart health, says Harvard study.

PMID- 24432449
TI  - Harvard research finds protective link between most cancers and Alzheimer's
      disease.

PMID- 24432450
TI  - Read a book, preserve your memory.

PMID- 24432451
TI  - 10 tips to prevent injuries when you exercise. How to work out safely so you get
      all the health benefits without the aches and strains.

PMID- 24432452
TI  - Ask the doctor. Every time I get a urinary tract infection, my doctor prescribes
      antibiotics. Is there any other way to treat my infections?

PMID- 24432453
TI  - Ask the doctor.  I've been feeling consistently down since my husband passed away
      last year.  What are my treatment options?

PMID- 24432454
TI  - Breast cancer:  when and how often to get screened.  How do you make sense of
      conflicting mammography guidelines?

PMID- 24432455
TI  - How to monitor--and lower--your blood pressure at home. Tracking your blood
      pressure readings over time will help you and your doctor make more educated
      treatment decisions.

PMID- 24432456
TI  - Eating for good vision.  Add these nutrients to your diet to preserve and protect
      your eyesight.

PMID- 24432457
TI  - Experts add second drug to breast cancer prevention regimen.

PMID- 24432458
TI  - Exercise--but avoid burnout.

PMID- 24432459
TI  - Staying mentally active throughout life preserves brain health.

PMID- 24432460
TI  - Higher BMI increases risk of gallstones.

PMID- 24432461
TI  - [Not Available].

PMID- 24432462
TI  - [Not Available].

PMID- 24432463
TI  - Abstracts of the 75th Annual Meeting of the Japanese Society of Hematology.
      October 11-13, 2013. Sapporo, Japan.

PMID- 24432464
TI  - Molecular mechanisms in cell signaling and gene expression. Abstracts. November 6
      7, 2013. Buenos Aires, Argentina.

PMID- 24432467
TI  - Electromagnetic waves in everyday life.

PMID- 24432468
TI  - Microwave assisted sintering of Al-Cu-Mg-Si-Sn alloy.
AB  - Microwave sintering has been a well-established technique to consolidate metal
      powders due to its instantaneous volumetric and rapid heating as compared to
      conventional heating. Al-3.8Cu-1Mg-0.8Si-0.3Sn (2712) alloy powders were
      compacted (200 and 400 MPa) and microwave sintered at different temperatures (570
      to 630 degrees C) under different atmospheres (vacuum, N2, Ar and H2). Increasing
      sintering temperature enhanced sintered density from 91% to 98%. Sintering under
      vacuum at 590 degrees C was more efficient with a densification parameter of 0.36
      followed by N2, Ar and H2. Regardless of the sintering condition, phase analysis
      via XRD revealed the presence of only alpha-Al peak attributed to lesser time
      available for diffusion of alloying elements. In addition, microstructural
      inhomogeneity leading to more intergranular melt formation was observed for all
      sintered compacts. Contrasting to densification, sintering in N2 resulted in
      better corrosion resistance.

PMID- 24432469
TI  - Inexpensive microwave leakage detectors--are they worth it? (A performance
      evaluation report).
AB  - Due largely to the misinformation spread by the blogosphere, many consumers are
      worried they may be harmed by the radiation leaking from microwave ovens. As a
      result, many have been purchasing and using inexpensive microwave oven leakage
      detectors. Several microwave engineers have tested some of these and found them
      to be inaccurate, often giving false-high or false-low readings. In our study, we
      examined a number of these selling for USD 79.95 and less, by comparison to
      professional equipment.

PMID- 24432470
TI  - Multiphysics numerical modeling of the continuous flow microwave-assisted
      transesterification process.
AB  - Use of advanced microwave technology for biodiesel production from vegetable oil
      is a relatively new technology. Microwave dielectric heating increases the
      process efficiency and reduces reaction time. Microwave heating depends on
      various factors such as material properties (dielectric and thermo-physical),
      frequency of operation and system design. Although lab scale results are
      promising, it is important to study these parameters and optimize the process
      before scaling up. Numerical modeling approach can be applied for predicting
      heating and temperature profiles including at larger scale. The process can be
      studied for optimization without actually performing the experiments, reducing
      the amount of experimental work required. A basic numerical model of continuous
      electromagnetic heating of biodiesel precursors was developed. A finite element
      model was built using COMSOL Multiphysics 4.2 software by coupling the
      electromagnetic problem with the fluid flow and heat transfer problem. Chemical
      reaction was not taken into account. Material dielectric properties were obtained
      experimentally, while the thermal properties were obtained from the literature
      (all the properties were temperature dependent). The model was tested for the two
      different power levels 4000 W and 4700 W at a constant flow rate of 840ml/min.
      The electric field, electromagnetic power density flow and temperature profiles
      were studied. Resulting temperature profiles were validated by comparing to the
      temperatures obtained at specific locations from the experiment. The results
      obtained were in good agreement with the experimental data.

PMID- 24432471
TI  - Photocatalytic degradation of RhB with microwave prepared PbMoO4.
AB  - Synthesized PbMoO4 from H2MoO4 and Pb(NO3)2 with microwaves was compared, in
      terms of its photocatalytic activity as catalyzer for decomposing rhodamine B
      (RhB), against samples prepared by hydrothermal and sonochemical methods from the
      same precursors. Microwave synthesis lasted 20 minutes; hydrothermal, 10 minutes
      and sonochemical method, 1 hour. Xrays diffraction patterns show that PbMoO4
      prepared by these three routes is compounded by the same phase. It is found that
      microwave synthesized PbMoO4 particles are rounder, in an intermediate size (250
      nm), compared to sonochemical (100 nm) and hydrothermal (500 nm) routes;
      microwave particles also exhibit higher photocatalytic activity for degradation
      of RhB under a xenon lamp. This difference is not explicable in terms of surface
      area measurements, but could be explained by UV Light scattering by the rounder
      particles produced by means of the microwave processing, which are about one half
      size compared to the wavelength.

PMID- 24432472
TI  - Control of attenuation in microwaves processing to obtain uniform treatment of
      epoxy glass.
AB  - This work deals with thermal aspect of the microwaves processing by applying the
      dielectric effect of attenuation inversion of electromagnetic wave as a solution
      for uniform treatment. Interest is devoted to the description of electromagnetic
      and chemical thermal contributions present during microwave heating of a
      thermosat material. An analytic methods was complemented with experimental data
      obtained by DSC. The chemical heat contribution is modeled by two methods:
      analytical and an experimental. The composite was characterized in terms of the
      reaction progress. The coupled electromagnetic, chemical and thermal model show
      results that can be evaluated from the temperature evolution. There is an strong
      rise in the temperature in one point, which is due to the non uniformity of the
      heat-storage capacity along the composite to be treated. The region of validation
      of the model is also shown.

PMID- 24432473
TI  - Challenges to unity.

PMID- 24432474
TI  - A vision for CDA.

PMID- 24432475
TI  - A professional challenge.

PMID- 24432476
TI  - Rocked, rattled & challenged.

PMID- 24432477
TI  - Getting the job done.

PMID- 24432478
TI  - United we debate.

PMID- 24432479
TI  - CDA. California Dental Association 20th anniversary.

PMID- 24432480
TI  - [Clinical evaluation of inpatients with tuberculosis diagnosed after admission-
      comparison of characteristics of patients diagnosed with and without the acid
      fast bacillus test].
AB  - PURPOSE: To evaluate the clinical characteristics of patients in whom
      tuberculosis was not suspected before admission but was diagnosed after
      admission. METHODS: We enrolled 39 inpatients who were diagnosed with
      tuberculosis between April 2007 and March 2011 at Jichi Medical University
      Hospital. The patients were divided into 2 groups as follows: those who underwent
      a preadmission acid-fast bacillus (AFB) test (AFB group) and those who did not
      (non-AFB group). We retrospectively evaluated the clinical characteristics of
      these 2 groups of patients. RESULTS: A total of 22 patients and 17 patients
      comprised the non-AFB and AFB groups, respectively. The prevalence rates of
      malignancy (9 vs. 2 patients, p = 0.04), extrapulmonary tuberculosis without
      pulmonary tuberculosis (9 vs. 2 patients, p = 0.04), and smear-negative
      tuberculosis (16 vs. 7 patients, p = 0.04) were higher in the non-AFB group than
      in the AFB group. In contrast, the computed tomographic findings of the patients
      with pulmonary tuberculosis revealed that compared with the AFB group, the non
      AFB group had less consolidation (2 vs. 11 patients, p < 0.01) and fewer cavitary
      lesions (0 vs. 6 patients, p < 0.01) and more nodular lesions (8 vs. 2 patients,
      p < 0.01). We then divided the inpatients into groups with and without malignancy
      and compared their clinical characteristics. The mean interval from admission to
      diagnosis of tuberculosis was significantly longer in the patients with
      malignancy as an underlying disease than in those without malignancy (23.5 vs.
      10.5 days; p < 0.01). CONCLUSION: Malignancy was the most frequent underlying
      disease in the tuberculosis inpatients in the non-AFB group and could be the
      reason for the delayed diagnosis of tuberculosis.

PMID- 24432481
TI  - [Comparative study of the efficacy of the COBAS TaqMan and LAMP assay for the
      rapid diagnosis of tuberculosis].
AB  - OBJECTIVE; The COBAS TaqMan real-time polymerase chain reaction (PCR) assay
      (TaqMan assay) is a well-accepted and widely distributed molecular-based
      diagnostic test for tuberculosis. In the present study, we evaluated the efficacy
      of the LAMP assay (loopamp MTBC detection kit) as an alternative molecular-based
      diagnostic kit for tuberculosis, through comparison with the TaqMan assay. STUDY
      PERIOD AND METHODS: This study was conducted over a period of approximately 2
      months, between May and July 2012. We collected 48 samples (43 sputum, 2 gastric
      fluid, 2 pleural fluid, and 1 pus fluid samples) from patients who had been
      diagnosed with tuberculosis through the culture method, but had not received any
      treatment for more than one week. All samples were processed using the CC-E pre
      treatment reagent (Japan BCG) prior to performing the TaqMan and LAMP assay. For
      the TaqMan assay, 100 microL of supernatant was used after centrifugation at
      1,000 rpm for 1 minute, whereas 60 microL of the precipitate in the same sample
      was used for the LAMP assay. RESULTS: In total, 23 out of 48 samples were
      identified as positive for tuberculosis according to smear microscopy tests,
      among which 15, 4, and 4 samples had smear test scores or 1+, 2+, and 3+,
      respectively. All the samples that tested positive in the smear test, regardless
      of the score, also tested positive in both the TaqMan and TB-LAMP assays (100%).
      Of the 25 smear-negative samples, we noted that 16 tested positive by the TaqMan
      assay (64%), whereas 20 tested positive by the LAMP assay (80%). DISCUSSION:
      Compared with the TaqMan assay, the LAMP assay showed a higher positive rate
      among the smear-negative samples. We believe that this is because substances in
      the samples acted as co-precipitating agents, resulting in the presence of a
      larger number of bacteria in the precipitates than in the supernatants. Thus, the
      findings indicate that the application of the LAMP method to precipitates
      obtained following CC-E pre-treatments may lead to prompt diagnosis of
      tuberculosis, with a level of sensitivity comparable to that of culture tests.

PMID- 24432482
TI  - [A case of pleural tuberculoma with new pulmonary infiltration during anti
      tuberculosis therapy].
AB  - A 61-year-old woman who had received treatment for tuberculous pleurisy for 2
      months visited our outpatient clinic. Chest computed tomography (CT) showed the
      presence of a lens-shaped pleural mass with pulmonary infiltration, despite the
      decreased pleural effusion. Two weeks later, chest CT showed an increase in the
      size of the mass and expansion of the intrapulmonary shadow. Percutaneous CT
      guided lung biopsy was performed, and histopathological examination revealed
      granulomatous inflammation without caseous necrosis or acid-fast bacilli. Sputum
      culture was negative for acid-fast bacilli. Anti-tuberculosis medication was
      continued, and the lesions eventually resolved. These lesions were diagnosed as
      pleural tuberculomas, and the intrapulmonary infiltration was considered to be
      due to the paradoxical worsening of the patient's condition.

PMID- 24432483
TI  - [Public health nurse support at initial community DOTS meetings with non
      hospitalized tuberculosis patients--comparison of patients who did and did not
      complete treatment].
AB  - PURPOSE: This study focused on the initial meeting between public health nurses
      and TB patients to investigate the detection of patients' needs and the support
      provided by public health nurses during the meeting, with the aim of successfully
      implementing a directly observed treatment short course (DOTS) strategy for the
      community. METHODS: A self-administered questionnaire was sent to nurses
      responsible for community DOTS strategy for TB in Aichi, Gifu, Mie, and Shizuoka
      prefectures in the Tokai region in order to collect the following information
      concerning the initial meeting between public health nurses and TB patients:
      nurses' characteristics, patient characteristics, information collected by the
      nurses, concerns expressed by patients, and specific support provided by the
      nurses. Data collected were compared between patients who completed TB treatment
      (complete treatment group) and those who did not (incomplete treatment group).
      RESULTS AND DISCUSSION: Valid responses were obtained from 42 public health
      nurses regarding 158 TB patients. The incomplete treatment group had a high
      proportion of patients who received no support from their families, had irregular
      lifestyles, or had financial problems. There were discrepancies between the
      information collected by public health nurses and patients' concerns. It was also
      revealed that public health nurses provided more specific support and a wider
      range of support to the incomplete treatment group, suggesting that public health
      nurses give specific support in the initial meeting to patients who were likely
      to discontinue TB treatment, thereby motivating them to complete the treatment.
      CONCLUSIONS: It is essential to arrange initial public health nurse-patient
      meetings at an early stage to build patients awareness of the disease and the
      importance of treatment adherence. Continuous support is crucial until the
      patients complete treatment.

PMID- 24432484
TI  - [Clinicoradiological diagnosis of pulmonary tuberculosis that understood the life
      of a patient].
AB  - This review discusses the clinicoradiological diagnosis of pulmonary
      tuberculosis. To make a differential diagnosis between pneumonia and
      mycobacterial infections, it is very important to analyze the radiological
      findings of inflammatory lung diseases based on normal anatomical structures. If
      clinicoradiological analyses could make these differentiations, the appropriate
      treatment strategy for respiratory infections could be established. To accomplish
      this, exact orientations of pulmonary lobulus, acinus, and miliary nodule are
      very important. Then, through analyzing chest CT findings and distribution
      patterns based on normal anatomical structures, estimation of Mycobacterium
      tuberculosis infection could be possible. To differentiate infections caused by
      Mycobacterium tuberculosis from other respiratory diseases, several important
      criteria have been demonstrated. In addition, activity of pulmonary tuberculosis
      as well as smear-positivity could be analyzed radiologically. The HRCT patterns
      described allow classification of disseminated tuberculosis according to the
      mechanism of spread (haematogenous and/or bronchogenic).

PMID- 24432485
TI  - Why dismantling the safety net for children with disabilities and their families
      is a poor idea.

PMID- 24432486
TI  - An examination of the psychometric properties of the Vicarious Trauma Scale in a
      sample of licensed social workers.
AB  - Vicarious trauma (VT) involves affective distress and shifts in cognitive schemas
      following secondary exposure to traumatic material. The Vicarious Trauma Scale
      (VTS) is a brief measure designed to assess distress resulting from such exposure
      and has potential as a screening tool for VT in practice and educational
      settings. The current study is the first examination of the psychometric
      properties of the VTS in a sample of social workers (n = 157) collected in a
      cross-sectional survey. Results from item response models (IRM) and confirmatory
      factor analysis (CFA) suggest the VTS has good to excellent psychometric
      properties and could be a general screening tool for exposure to traumatic
      material or distressed clients and a measure of the affective and cognitive
      impact of such exposure. Both CFA and IRM approaches suggest a two-dimensional
      solution for the VTS, corresponding to cognitive and affective components.
      Implications for research and applications to practice are discussed.

PMID- 24432487
TI  - Racial disparities in the use of physical restraints in U.s. nursing homes.
AB  - The use of physical restraints in nursing homes among black and white residents
      was examined on the basis of data from the 2004 National Nursing Home Survey to
      determine if black residents were more susceptible to the use of physical
      restraints. Odds ratios acquired through logistic regression are provided with 95
      percent confidence intervals. Findings revealed that black residents are more
      likely than white residents to be restrained with bed rails, side rails, and
      trunk restraints. Findings suggest that racial disparities exist in the use of
      physical restraints. Implications for practice, policy, and research are
      discussed.

PMID- 24432488
TI  - Validation of the Chinese version of the Modified Caregivers Strain Index among
      Hong Kong caregivers: an initiative of medical social workers.
AB  - Family caregivers may often experience caregiving stress and burden. To
      systematically assess this issue, medical social workers may need to use a brief
      and valid measurement in their practice. In the Hong Kong Chinese context, one
      additional challenge is to examine whether a measurement developed in the West is
      valid for Hong Kong Chinese caregivers. Thus, medical social workers in Hong Kong
      initiated this research study to validate the Chinese version of the Modified
      Caregiver Strain Index (C-M-CSI). A total of 223 Chinese caregivers of patients
      with various chronic illnesses were recruited for this validation study. C-M-CSI
      demonstrated good reliability (Cronbach's alpha coefficient = .91), concurrent
      validity with the Chinese version of the Caregiver Burden Inventory, and
      discriminant validity with the Chinese version of the Meaning in Life
      Questionnaire. Factor analysis yielded a single factor as the original M-CSI,
      which explained 49 percent of variance. Construct validity was shown by
      differentiating spousal and nonspousal caregivers, as well as caregivers of
      patients with and without behavioral problems. C-M-CSI is recommended as a brief
      and valid measurement that can be used by medical social workers in assessing the
      caregiving strain of Chinese caregivers of patients in Hong Kong.

PMID- 24432489
TI  - The Caregiver Well-Being Scale: developing a short-form rapid assessment
      instrument.
AB  - The Caregiver Well-Being Scale (CWBS) is a 43-item instrument that was designed
      in the 1990s to help family caregivers, clinicians, and researchers identify
      areas ofcaregiver strength and areas in which additional support is needed. This
      article describes the development of a 16-item version of the CWBS and discusses
      the methods used in testing the psychometric properties of the shortened version
      in a sample of 493 family caregivers. It concludes that the shortened version is
      valid, reliable, and easier to use than the original version but has the same
      goals and continues to be applicable in research and clinical settings.

PMID- 24432490
TI  - Intimate partner violence exposure in early childhood: an ecobiodevelopmental
      perspective.
AB  - Approximately 15.5 million children in the United States reside in households in
      which interpersonal violence is recurrent. Young children are more likely than
      older children to be present in the home when violence between adults occurs. In
      a recent technical report, the American Academy of Pediatrics renewed its call to
      invest in research and intervention resources for children younger than five
      years of age. The report also outlined the ecobiodevelopmental (EBD) framework,
      an emerging cross-disciplinary understanding of stress and coping response in
      very young children. The EBD framework explains how unresolved stress experienced
      by infants, toddlers, and preschoolers has toxic effects on their development.
      The framework could also expand opportunities for social workers who have an
      interest in research and clinical work involving very young children exposed to
      violence.

PMID- 24432491
TI  - Better colon cancer care for extremely poor Canadian women compared with American
      women.
AB  - Extremely poor Canadian women were recently observed to be largely advantaged on
      most aspects of breast cancer care as compared with similarly poor, but much less
      adequately insured, women in the United States. This historical study
      systematically replicated the protective effects of single- versus multipayer
      health care by comparing colon cancer care among cohorts of extremely poor women
      in California and Ontario between 1996 and 2011. The Canadian women were again
      observed to have been largely advantaged. They were more likely to have received
      indicated surgery and chemotherapy, and their wait times for care were
      significantly shorter. Consequently, the Canadian women were much more likely to
      experience longer survival times. Regression analyses indicated that health
      insurance nearly completely explained the Canadian advantages. Implications for
      contemporary and future reforms of U.S. health care are discussed.

PMID- 24432492
TI  - [Easier for students to reproduce facts than to draw their own conclusions].

PMID- 24432493
TI  - [Is it ethical to compensate for kidney donation?].

PMID- 24432494
TI  - [New and old medications for croup and seizures in children. Oral dexamethasone
      and buccal midazolam may provide better treatment].

PMID- 24432495
TI  - [The number of claims reported to the Insurance Company LOF for patient injuries
      after treatment of appendicitis is low, but there should be even fewer].

PMID- 24432496
TI  - [Hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency.
      Condition with diagnostic pitfalls].

PMID- 24432497
TI  - [Previous cesarean section increases the risk of serious pregnancy complications.
      Descriptions of two cases with life-threatening bleeding].

PMID- 24432498
TI  - [It is possible to reduce drug-drug interactions. Interactions were corrected
      frequently by patient-specific letters to general practitioners].

PMID- 24432499
TI  - [Drug list as cognitive support provided detailed information relating to drug
      use. Comparison of two methods for the investigation of opioid dependence].

PMID- 24432500
TI  - [Investigate the medical education all the way to specialist certification].

PMID- 24432501
TI  - [Use private health care in internship education].

PMID- 24432502
TI  - [Reply on TWAR: Lies, damned lies and registry data].

PMID- 24432503
TI  - [Reply: Interesting information].

PMID- 24432504
TI  - [Genes tell of the Neanderthal role in human evolution].

PMID- 24432505
TI  - Emergency management of blunt chest trauma in children: an evidence-based
      approach.
AB  - Pediatric trauma is commonly encountered in the emergency department, and trauma
      to the head, chest, and abdomen may be a source of significant morbidity and
      mortality. As children have unique thoracic anatomical and physiological
      properties, they may present with diagnostic challenges that the emergency
      clinician must be aware of. This review examines the effects of blunt trauma to
      the pediatric chest, as well as its relevant etiologies and associated mortality.
      Diagnostic and treatment options for commonly encountered injuries such as
      pulmonary contusions, rib fractures, and pneumothoraces are examined.
      Additionally, this review discusses rarely encountered--yet highly lethal--chest
      wall injuries such as blunt cardiac injuries, commotio cordis, nonaccidental
      trauma, and aortic injuries.

PMID- 24432506
TI  - She would turn a question mark in the student's head into a light bulb!

PMID- 24432507
TI  - Simultaneous infection with Shigella sonnei and Vibrio cholerae in a young child.
AB  - A 20-month-old infant presented to the emergency department with diarrhea and
      vomiting of six days duration. Blood, stool and urine specimens were collected
      for both bacteriological culture and parasitic workup. Concurrent infections with
      both Shigella sonnei and Vibrio cholerae were determined to be the cause of the
      infectious diarrhea. This case illustrates the importance of the microbiology
      laboratory in detecting infrequently seen enteric pathogens. We will also review
      the pathogenesis and laboratory diagnosis of Vibrio cholerae and Shigella sonnei.

PMID- 24432508
TI  - A case of Bordetella holmseii endocarditis in an asplenic pediatric patient.

PMID- 24432509
TI  - Evaluation of a cost effective broth and selective agar combination for the
      detection of MRSA and Staphylococcus aureus from surveillance specimens using
      regular workflow.
AB  - OBJECTIVE: To evaluate the use of selective agar and broth combination in a
      regular laboratory daily workflow. DESIGN: Swabs from 173 surveillance specimens
      were inoculated onto half of the Bio-Rad MRSASelect (M), SaSelect (S) and Sheep
      Blood agars (SBA) and the swab placed in the LIM broth. After overnight
      incubation, 10 microL of the LIM broth was inoculated onto the other half of the
      three agars and incubated overnight. All the and examined worked after agars were
      up approximate 14-18 hours of incubation for day one and two according to the
      regular workflow of the laboratory, without incubating for the full 24 hours for
      each incubation day. M agar and SBA were evaluated for Methicillin-Resistant
      Staphylococcus aureus (MRSA), while the S agar was evaluated for Staphylococcus
      aureus (SA) based on typical colony morphology development. Colonies on the SBA
      were picked and processed for definitive identification and cefoxitin
      susceptibility result. SETTING: Trinity Medical Center, a community hospital with
      network hospitals PATIENTS: Patient admitted to the hospital submitted swab for
      surveillance culture RESULTS: There were a total of 29 MRSA isolated in the
      study. On day one, both M agar and SBA detected 14 MRSA (48.3%) and on day two, M
      agar detected 10 (82.7%), while SBA detected 8 (75.8%) additional MRSA. LIM broth
      added 5 more MRSA to both agars on day 2, to give M agar a total of 29 (100%) and
      SBA agar a total of 27 (93.1%) of MRSA from the 173 specimens. There were a total
      of 62 SA isolated. Both the S agar and SBA isolated 34 (54.8%) on day one and 15
      more (79%) on day two. The LIM broth added an additional 13 SA for both agars on
      day two. CONCLUSION: Using half of the agar plate for the initial swab and the
      other half for the broth creates an economic strategy for the detection of MRSA
      using the M agar and SA using the S agar. Both the M and S agars provided
      excellent identification and recovery of MRSA or SA based on color and colony
      morphology unless the colony was too young for color development. The color
      morphology from the M and S agars was distinguishable overnight after being
      subcultured from LIM broth. Working up the specimen according to the workflow of
      the laboratory without having to wait for each plate to incubate a full 24 hours,
      can still detect all the targeted organisms within 2 workdays using this cost
      effective strategy.

PMID- 24432510
TI  - Introduction to lymphoproliferative disorders in adults.

PMID- 24432511
TI  - A case-based review of chronic lymphocytic leukemia.

PMID- 24432512
TI  - Plasma cell myeloma: literature review and case study.

PMID- 24432513
TI  - Redefining patient safety in the clinical laboratory. Introduction.

PMID- 24432514
TI  - Improving patient safety and healthcare quality in the 21st century--competencies
      required of future medical laboratory science practitioners.
AB  - Healthcare quality has yet to meet the aims of the Institute of Medicine (IOM)
      with respect to safety, effectiveness, patient-centeredness, efficiency,
      timeliness and equity. No professional curricula adequately prepare future
      healthcare practitioners-including medical laboratory science professionals-with
      all competencies necessary to deliver quality healthcare. Practicing evidence
      based medicine, focusing on quality improvement, using information technology,
      delivering patient-centered care and working as part of interdisciplinary teams
      are identified by the IOM as the five core competencies that every healthcare
      practitioner needs to effectively provide healthcare. Medical laboratory science
      educators need to incorporate patient safety concepts into the curricula and
      include assignments to develop the IOM competencies in order to adequately
      prepare future practitioners to effectively practice medical laboratory science
      in the healthcare system of the 21st century.

PMID- 24432515
TI  - Using performance tasks employing IOM patient safety competencies to introduce
      quality improvement processes in medical laboratory science education.
AB  - In order to contribute to improved healthcare quality through patient-centered
      care, laboratory professionals at all levels of practice must be able to
      recognize the connection between non-analytical factors and laboratory analysis,
      in the context of patient outcomes and quality improvement. These practices
      require qualities such as critical thinking (CT), teamwork skills, and
      familiarity with the quality improvement process, which will be essential for the
      development of evidence-based laboratory science practice. Performance tasks (PT)
      are an educational strategy which can be used to teach and assess CT and
      teamwork, while introducing Medical Laboratory Science (MLS) students at both
      baccalaureate and advanced-practice levels to the concepts of quality improvement
      processes and patient outcomes research. PT presents students with complex,
      realistic scenarios which require the incorporation of subject-specific knowledge
      with competencies such as effective team communication, patient-centered care,
      and successful use of information technology. A PT with assessment rubric was
      designed for use in a baccalaureate-level MLS program to teach and assess CT and
      teamwork competency. The results indicated that, even when students were able to
      integrate subject-specific knowledge in creative ways, their understanding of
      teamwork and quality improvement was limited. This indicates the need to
      intentionally teach skills such as collaboration and quality system design. PT
      represent one of many strategies that may be used in MLS education to develop
      essential professional competencies, encourage expert practice, and facilitate
      quality improvement.

PMID- 24432516
TI  - Evidenced based practice: classroom to clinical laboratory.
AB  - Evidence based practice (EBP) can be incorporated into the curriculum of Medical
      Laboratory Science (MLS) Programs. Current components of curriculum can include
      EBP in pre-analytic, analytic, and post-analytic topics. Discussion of EBP topics
      in the classroom using practices assessed through the Laboratory Medicine Best
      Practices Initiative (LMBP) of the U.S. Centers for Disease Control and
      Prevention will give students a clear understanding of EBP and how it is used in
      the clinical laboratory for improved health care quality. Student involvement in
      Quality Improvement projects to improve laboratory performance and patient
      outcomes can be developed through capstone projects. Examples of clinical
      projects and application of EBP into the MLS curriculum are discussed.

PMID- 24432517
TI  - [Centenary of the publication of "The epiphytic bromeliads considered biological
      environment" (1913) Picado Twight, a pioneer of the ecology of bromeliads].

PMID- 24432518
TI  - [Alfred Russel Wallace on the centenary of his death].

PMID- 24432519
TI  - Isolation and characterization of osmotolerant bacteria from thar desert of
      western Rajasthan (India).
AB  - The Thar Desert harsher environment harbors a limited diversity of life forms due
      to extreme conditions like low moisture of sandy soils and high soil temperature.
      In the present study, osmotolerant bacteria from the Thar soils were isolated and
      characterized. Bacteria were isolated from 20 soil samples (100 g), collected
      from sand dunes, suspended in water and absolute alcohol. A total of 11
      biochemical and morphological tests were carried out for generic identification
      of bacteria. Osmotic tolerance capacity of isolates was examined on glycerol,
      NaCI and alcohol; and sequencing of 16S rRNA gene was also performed for
      bacterial identification. 16S to 23S rRNA internal transcribed spacer analysis
      (RISA) was done for phylogenetic analysis of isolates. The soil suspended in
      water contained 2.5 x 10(6) bacteria/g of soil while alcohol suspended soil had
      4.4 x 10(4) bacteria/g. The 24 bacterial isolates were found tolerant to 26%
      glycerol, 14% NaCI and 10% of alcohol, and 22 out of 24 isolates were found Gram
      positive. The results showed that 45.83% and 41.67% bacteria belong to Bacillus
      spp. and Corynebacterium spp., respectively, while Acinetobacter spp., Aeromonas
      spp. and Staphylococcus spp. were in equal proportion (4.16% each). Six isolates
      were selected for 16S rRNA gene sequencing and five were found 95% similar with
      Bacillus licheniformis whereas one isolate was identified as B. subtilis. All the
      isolates showed good growth up to 50 degrees C with gradual reduction on
      subsequent increment of temperature. Out of 24 isolates, six could survive at 65
      degrees C while one isolate could grow at 63 degrees C. Growth kinetic studies
      revealed that the reduction in generation time in solute(s) and temperature
      stress was more as compared to generation time in plain medium. This study
      suggests that virgin sand dunes may be a rich source of bacteria, tolerant to
      osmotrophic solutes, and can be examined for plant growth promotion activity in
      agriculture. Moreover, study might help to resolve the tactic adopted by microbes
      to defeat desiccation induced by various types of solutes.

PMID- 24432520
TI  - [New Liolaemus (Iguania: Liolaemidae) with a new morphological character from the
      border between Argentina and Chile].
AB  - Liolaemus belongs to the Eulaemus subgenus, that is included in the Liolaemus
      montanus group or section, and is distributed in Argentina, Bolivia, Chile and
      Peru. The species members of this clade inhabit arid and high altitude
      environments, usually above 2800 m, and have a strong tendency to herbivory and a
      viviparous reproductive type. In a herpetological expedition to the Salta
      Province highlands, Argentina, in April 2012, we collected individuals of this
      new species for their description. The specimens were collected with loop,
      slaughtered by anesthesia and deposited in the herpetological collection of
      Fundacion Miguel Lillo in Tucuman (FML). To characterize this new taxon, we
      analyzed 144 external morphological characters, referring primarily to lepidosis,
      color pattern, and body proportions, comparing with data from 66 constituent
      species of the L. montanus group (45 taxa from collection specimens and 21 from
      literature). Description of the colors in life was made in the field and based on
      photographs taken during the capture. The species described in this work inhabits
      a very narrow mountain range area in Salta Province (Argentina), and the Atacama
      Region (Chile), always above the 3600 m. This new taxon shows characteristics of
      lepidosis and color patterns clearly different from the other species members of
      the L. montanus group: the maximum snout-vent length is 72.9 mm; shows 74-96
      scales around midbody, 89-104 dorsal scales between the occiput and hind limbs,
      92-109 ventrals, precloacal pores are evident in both, males and females, and
      supernumerary pores in males. Also, the presence of postcloacal pores stands out
      as unique among all Liolaemus. This is a new character, not only for the genus,
      but also to all Reptilia, becoming a morphological discovery of great importance,
      since in reptiles only precloacal and femoral pores are known. Based on our field
      observations, this new Liolaemus is related to rocky environments, which are used
      as refuge by this omnivorous species, and when handled, very aggressive males.

PMID- 24432521
TI  - The bird community in naturally regenerating Myracrodruon urundeuva
      (Anacardiaceae) forest in southeastern Brazil.
AB  - Conservation and restoration projects involving abandoned cattle pastures pose
      several challenges. Restoration ecologists recognize that natural restoration is
      possible, but few species can successfully colonize degraded pastures. The aim of
      the present study was to evaluate whether land colonized by the tree Myracrodruon
      urundeuva increase the amount of habitat available for bird communities in
      Southeastern Brazil. We used fixed point counts within a 50 m radius to compare
      the richness and composition of the bird community inhabiting naturally
      regenerated M. urundeuva with that an adjacent native forest remnant and a forest
      restored with planted Acacia spp. We recorded a total of 68 bird species. The M.
      urundeuva forest was able to provide valuable habitat for bird species, including
      more forest species, in comparison with the Acacia planting. These results
      indicate that M. urundeuva is a useful species for the ecological restoration of
      degraded pasture land.

PMID- 24432522
TI  - [Diversity of birds in the Agricultural Center Cotove, Santa Fe de Antioquia,
      Colombia].
AB  - Fragmentation of natural habitats is a central concern of biodiversity
      conservation and is considered a significant factor contributing to species loss
      and populations decline. We studied this in Cotove Agricultural Center in the
      municipality of Santa Fe de Antioquia (Colombia),where the conversion of natural
      forests to different land use systems, has limited the amount of available
      habitat. With the aim to describe the effect of habitat loss on bird presence in
      five land uses (fruiting trees, silvopastoral systems, secondary forest, pasture
      low density of trees and grass cutting) in this area, we studied bird diversity
      using two methods: fixed point counts and mist nets to analyze the influence of
      land use in the composition, richness and abundance of birds present were
      studied. A total of 6633 individuals of 101 species were observed of which 11
      species were migratory. The insectivorous and frugivorous foraging guilds were
      better represented. The Shannon index indicated the highest values of alpha
      diversity for the silvopastoral system, and the fruit with the lowest. The
      grazing and silvopastoral land systems shared more species with low tree density.
      The importance of the environmental heterogeneity found is highlighted as a
      positive factor for bird species richness, mostly of low and middle habitat
      specificity, and preferably from edge habitats and open areas. In order to
      preserve natural regeneration and connectivity between different land use types,
      and to promote stability of bird species populations, some management actions
      should be implemented in the area.

PMID- 24432523
TI  - [Vertebrate mortality in the Guanare-Guanarito road, Portuguesa state,
      Venezuela].
AB  - Roads directly or indirectly affect the structure, dynamics and function of
      ecosystems that they traverse. Most studies on the effect of roads on wildlife
      focus on the evaluation of mortality of vertebrates by vehicle collisions.
      Despite the extensive road network that exists in Venezuela, studies of wildlife
      mortality in them are scarce. In this paper, we analyzed the temporal and spatial
      pattern of vertebrate's collisions along the road Guanare-Guanarito, in
      Portuguesa state. We travelled 26 times between these towns (74 km) to localize
      dead vertebrates, at a speed of 50-60km/h. of those trips were conducted from
      March 13 to October 26, 2010, and 10 additional trips from December 7, 2009 to
      December 14, 2010; these ones, with the aim to include months and seasons that
      were insufficiently sampled during the first period. The elapsed time between
      trips varied from 14 to 37 days. The total distance traveled was 1 924 km. Dead
      animals found amounted 464 individuals, 66 of them were birds (25 identified
      species), 130 mammals (15 species) and 268 reptiles (18 species). The species
      with the highest number of individuals were the snake Leptodeira annulata
      (n=119), the oppossum Didelphis marsupialis (n=39) and the spectacled caiman
      Caiman crocodilus (n=33). Excluding domestic animals, the rate of road-killed
      vertebrates was 0.2282 indiv./km, a figure 28.3% higher than previous studies in
      the same road. Changes in the relative number of collisions for some species,
      respect to the numbers reported 20 years ago, were linked to the increase in
      traffic flow and changes in land use. Road segments with collision rates higher
      than expected by chance were identified. Collition by cars may be the principal
      cause of mortality for species like the tamandua (Tamandua tetradactyla) and the
      giant anteater (Myrmecophaga tridactyla), the last considered a vulnerable
      species. Some basic measures are proposed to reduce wildlife mortality on the
      road.

PMID- 24432524
TI  - [Population dynamic of Donax denticulatus (Bivalvia: Donacidae) at Carenero
      Beach, Southeastern Cuba].
AB  - Bivalve molluscs of Donax genus are a very important component of macro
      invertebrate assemblages of sandy beaches, and some species are of commercial
      value in different countries. Although in Cuba Donax denticulatus is not a
      currently exploited species, the information concerning a stock assessment is a
      basic step for future use of this resource. With the aim to generate new data on
      this species structure, growth and secondary production, monthly samples of D.
      denticulatus were taken from a beach of the Southeastern coast of Cuba, from
      February to December 2008. Samples were taken from four stations located along
      the beach; three strata were marked (P1, P2 and P3) per station across the
      intertidal zone. Three replicated samples of sediments were taken from each
      stratum with a 0.025 m2 PVC core and were posteriorly sieved with a 1 mm mesh.
      Histograms of shell length were constructed based on 1 mm intervals and growth
      parameters were estimated using ELEFAN I routine of FISAT. Mean density ranged
      from 146.67-855.55 ind./m2 and no differences were found among months (ANOVA, p >
      0.05) but among strata (Scheffe, p < 0.05). An association of recruits, young and
      adults abundances with the strata (chi2, p < 0.01) was found. Most of the
      recruits were found in the upper strata while young and adult individuals were
      abundant in the mid-lower strata. Size frequency histograms of this population
      showed recruitment between March-June. Growth parameters estimated by Von
      Bertalanffy were Linfinity = 27.5 mm and K = 1.5/year; and the life spam was
      estimated in 1.5 years. Using the length-converted catch curve, the mortality
      rate (Z) was estimated in 4.97/year. Based in terms of Ash free dry mass (AFDM),
      mean biomass was estimated in 0.47 g/m2.year and the somatic production in 12.4
      g/m2.year. The renewal rate (P/B) estimated for this population was 26.38, the
      highest among other Donax populations. High densities, fast growth and high
      somatic production indicate that this population can be exploited for fishing
      purposes for which some management measures are proposed.

PMID- 24432525
TI  - Biology of Kalipharynx sp. (Trematoda: Digenea) metacercariae in Biomphalaria
      (Gasteropoda: Planorbidae) from northeastern Argentina.
AB  - In Argentina, no ecological studies have been reported on the infection
      parameters of Kalipharynx sp. metacercariae in planorbid snails. To this end, the
      aims of this study were: (i) to provide information on the population biology of
      Kalipharynx sp. metacercariae in the planorbid snails Biomphalaria tenagophila
      and B. occidentalis through the study of prevalence and intensity of larval
      infection during a seasonal cycle; (ii) to evaluate the effects of host shell
      size on prevalence and infection intensity, (iii) to evaluate the effect of
      infection intensity on cyst size. Samples were taken between June 2010 and April
      2011 (encompassing all seasons) from a subtropical permanent pond in Corrientes
      City, Corrientes, Argentina. A total of 362 metacercariae (n=262 and n=100; from
      B. tenagophila and B. occidentalis respectively) were collected from 616 snails
      (n=466 and n=150 from B. tenagophila and B. occidentalis respectively). The
      metacercarial cysts were found in the digestive gland, mantle cavity, intestine
      and ovotestis. B. tenagophila showed a range of infection from 1 to 60 cysts per
      snail (mean = 4.5 +/- SD=9.9), and cyst diameter ranging between 255 and 705
      microm (466.4 +/- 119); while, B. occidentalis showed a range of infection from 1
      to 23 (5.5 +/- 5.6), and cyst diameter ranging between 310 to 900 microm (554.5
      +/- 150). Results obtained indicated that, although absent in autumn,
      metacercariae of Kalipharynx sp. were present most of the year in both species of
      Biomphalaria, showing high values in both warm-season. Furthermore, both the
      infection intensity and host shell size varied significantly between seasons,
      although no seasonal variation was observed with respect to metacercarial cyst
      size, suggesting the possibility of more than one peak of cercariae emergence
      during the year. The prevalence of infection was significantly and positively
      correlated with snail size in both host species (p<0.05). The smallest host size
      class harbouring a metacercarial infection was 7.1-8.0 mm and 11.1-12.0 mm in B.
      tenagophila and B. occidentalis, respectively. The mean intensity of infection
      was positively correlated with snail size, but this relation was significant only
      in B. tenagophila (p < 0.05). However, non-significant negative correlations were
      observed for intensity of infection vs. cyst size in both host species (p >
      0.05). The results of this study show a significant influence of host size on
      prevalence and infection intensity, and a tendency towards density-dependent
      reductions in the growth of cysts. This is the first study in Argentina analyzing
      the population biology of Kalipharynx sp. metacercariae.

PMID- 24432526
TI  - [Density, size structure and reproductive activity of the pink conch Eustrombus
      gigas (Mesogastropoda: Strombidae) in Banco Chinchorro, Mexico].
AB  - The pink conch Eustrombus gigas is an important fisheries resource. At the
      regional level in the Caribbean, over-exploitation and habitat destruction have
      caused a decrease in the abundance of this resource. In order to provide
      necessary information for the species management in Mexico, this work aimed to
      analyze the total density, adult density, size structure and reproductive
      behavior of pink conch population at Banco Chinchorro during 2009-2010. Data from
      three seasons were obtained (rainy, dry and cold fronts periods) in three areas:
      Norte (North), Centro (Center) and Sur (South). The organisms were separated into
      two groups: (a) the criteria based upon legal harvest in Mexico: legal size
      conchs (siphonal length > 200 mm) and illegal size conchs (siphonal length < 200
      mm), and (b) the criteria based upon sexual maturity using the 15 mm lip
      thickness standard: lip < 15 mm as juvenile conch and lip > or = 15 mm as adult
      conch. Copulation, spawning, egg masses and aggregations were evaluated as
      reproductive evidences. The highest total density was observed during the dry
      season with 384ind./ha, and the lowest during the rainy season with 127ind./ha.
      The highest density was reported at Sur (385ind./ha) and the lowest at Norte
      (198ind./ ha). The highest adult density was observed during the rainy season
      (8.33ind./ha), and the lowest occurred in the dry season (6.1 ind./ha). Adult
      density values were 5.55, 7.05 and 8.33ind./ha for Centro, Sur and Norte areas,
      respectively. Adult densities were lower than the threshold needed for
      reproduction, and 42% of the population may be vulnerable to fishing, as they had
      the minimum size for catch (Lsi 200 mm). Furthermore, only 2.2% of the population
      reached a Gl > 15 mm as sexual maturity indicator. During the study period, only
      six evidences of reproductive activity were observed. The smaller densities
      reported at Banco Chinchorro may cause reproduction events to be almost absent
      which in turn is sufficient evidence to show that the Allee Effect is acting on
      the queen conch population and there is an urgent need of fishery closure. Three
      important points were proposed for management of queen conch at Banco Chinchorro:
      total closure of fishing, systematic assessment of the conch population and the
      implementation of conch fishing refuge.

PMID- 24432527
TI  - Declining densities and reproductive activities of the queen conch Strombus gigas
      (Mesogastropoda: Strombidae) in Banco Chinchorro, eastern Caribbean, Mexico.
AB  - Queen conch is a gastropod inhabiting the Caribbean Sea, it represents the second
      largest fishery after the spiny lobster, but it has been extensively captured in
      the area. In order to know its population status in Chinchorro Bank, we
      determined conch density changes and its effects on reproductive activities,
      between July and November 2009. For this, data on conch density, morphology and
      reproductive activities were obtained from 15 sites within three fishing zones,
      and compared with previously collected data (1990, 1992, 1994, and 1997). Data
      showed that adult density decreased with time, from 10,700 ind./ha in 1990, to
      198 ind./h in 2009. Neither egg masses nor spawns were found and mating was only
      observed once in July 2009. In July, adult (lip>4 mm) density in the Southern
      zone was 23 ind./ha whereas in the Northern zone and Central zone densities were
      15 and 9ind./ha respectively. In November, density was somewhat higher: Southern
      zone 96 ind./ha; Central zone 39 ind./ha and Northern zone had 38ind./ha. In
      July, mean shell length was 170.80 +/- 46.28 mm, with a higher median abundance
      at 180-189 mm. In November, higher frequency was 187.63 +/- 45.14 mm, maximumat
      210-219 mm interval. For the last 10 years period, mean adult conch densities
      have diminished in each zone, which might be the main cause of decreased
      reproductive activities of the conch at Banco Chinchorro. It is therefore an
      immediate need to analyse the management plan for this species in this Reserve
      and perhaps to promote a re-population of queen conch and culture activities.

PMID- 24432528
TI  - Regional diversity of amphipoda in the Caribbean Sea.
AB  - The order Amphipoda is one of the most diverse within Peracarids, and comprises
      6950 described marine species. Amphipod research in the Caribbean Sea began in
      the late 1800s, but has increased significantly since 1980. In this study, we
      analized the amphipod biodiversity (Caprellidea, Gammaridea, Hyperiidea, and
      Ingolfiellidea) of the Caribbean Sea. For this, we compiled available data on
      species diversity of marine amphipods (data bases: WoRMS and OBIS and published
      species lists) into a comprehensive taxonomic list by country for the ecoregions
      of the Caribbean. Additionally, we analized the relative contribution of each
      country to regional diversity and the rate of discovery of new species. The
      Caribbean amphipod fauna is composed of 535 species within 236 genera and 73
      families for the higher taxon. The Western Caribbean ecoregion holds the largest
      diversity (282 species), while the Eastern Caribbean recorded the lowest one
      (73). Mexico and Venezuela recorded the largest number of species with 266 and
      206, respectively. Twelve countries had less than 50 species. The richest
      suborder is the Gammaridea with 381 species followed by the suborder Hyperiidea
      with 116. From the total of 535 amphipod species reported for the Caribbean
      region, 218 have the Caribbean as the holotype locality, and 132 are endemic
      (about 25% of the total). Areas of higher diversity seem to be concentrated along
      the Mexican Caribbean, Cuba and the Northern coast of South America (Venezuela
      Colombia); however, such pattern is most likely reflecting local collection
      efforts and taxonomic expertise rather than actual distribution. Knowledge of
      amphipod species is mostly limited to shallow, near-shore waters, with little
      infonnation available on the deep sea fauna. Regional research priorities for
      this group should be focused on completing shallow water coastal inventories of
      species in Central America and the Greater and Lesser Antilles. In addition,
      sampling the deep sea ecosystems should follow along with other particular
      habitats such as anchialine cave systems. It is also neccessary to increase
      ecological research efforts, mainly in some speciose suborders, including the
      Caprellidea and Hyperiidea, known to exhibit high diversity in other tropical
      localities.

PMID- 24432529
TI  - Population biology of the mangrove crab Ucides cordatus (Decapoda: Ucididae) in
      an estuary from semiarid northeastern Brazil.
AB  - The mangrove crab Ucides cordatus is an important resource of estuarine regions
      along the Brazilian coast. U. cordatus is distributed from Florida, U.S.A., to
      the coast of Santa Catarina, Brazil. The species plays an important role in
      processing leaf litter in the mangroves, which optimizes the processes of energy
      transfer and nutrient cycling, and is considered a keystone species in the
      ecosystem. Population declines have been reported in different parts of the
      Brazilian coast. In the present study we evaluated aspects of the population
      structure, sex ratio and size at morphological sexual maturity. We analyzed 977
      specimens collected monthly over 24 months (2010-2012), in a mangrove of the
      Jaguaribe River, in the municipality of Aracati on the East coast of Ceara state,
      Northeastern Brazil. The study area has a mild semiarid tropical climate, with
      mean temperatures between 26 and 28 degrees C. The area is located within the eco
      region of the semiarid Northeast coast, where mangroves occur in small areas and
      estuaries are affected by mesomareal regimes. The population structure was
      evaluated by the frequency distribution of size classes in each month, and the
      overall sex ratio was analyzed using the chi-square test. Size at morphological
      sexual maturity was estimated based on the allometry of the cheliped of the males
      and the abdomen width of the females, using the program REGRANS. The size
      frequency distribution was unimodal in both sexes. The overall sex ratio (M:F)
      (1:0.6) was significantly different from 1:1. Analysis of the sex ratio by size
      class showed that the proportion of males increased significantly from size class
      55-60 mm upward, and this pattern persisted in the larger size classes. In the
      smaller size classes the sex ratio did not differ from 1:1. The size at
      morphological sexual maturity was estimated at a carapace width (CW) of 52 mm and
      45 mm for males and females, respectively. Analysis of the population parameters
      indicated that the population of U. cordatus in the Jaguaribe River mangrove is
      stable. However, constant monitoring of the population is required to detect any
      changes in the population attributes that may affect this stability.

PMID- 24432530
TI  - Morphology and ultrastructure of the freshwater rotifer Brachionus bidentatus
      (Monogononta: Brachionidae) using scanning and transmission electron microscopy.
AB  - The study of sexual reproductive behavior supported by ultrastructural evidence
      is important in rotifers to describe differences among potential cryptic species.
      In this research, the morphology of the rotifer Brachionus bidentatus is
      described at the ultrastructural level, using electronic microscopy, together
      with a brief description and discussion of its sexual reproductive behavior. The
      characteristics of the (a) male, (b) the female, (c) the sexual egg or cyst, (d)
      the partenogenic egg, (e) the no-fecundated sexual egg (male egg), and (f) the
      trophi, were described. Another part of this research is dedicated to the
      ultrastructure of the sex cells of the male rotifer B. bidentatus. Samples were
      obtained from La Punta pond in Cosio, Aguascalientes, Mexico (22 degrees 08' N -
      102 degrees 24' W), and a culture was maintained in the laboratory. Fifty
      organisms, from different stages of the rotifer Brachionus bidentatus, were fixed
      in Formol at 4% and then prepared; besides, for the trophi, 25 female rotifer
      Brachionus bidentatus were prepared for observation in a JEOL 5900 LV scanning
      electronic microscope. In addition, for the observation of male sex cells, 500
      males of Brachionus bidentatus were isolated, fixed and observed in a JEOL 1010
      transmission microscope. Females of B. bidentatus in laboratory cultures had a
      lifespan of five days (mean+one SD = 4.69 +/- 0.48; N=13), and produced 4.5 +/-
      3.67 (N=6) parthenogenetic eggs during such lifespan. In the case of non
      fertilized sexual eggs, they produced up to 18 eggs (mean+one SD = 13 +/- 4.93;
      N=7). Sexual females produced a single cyst on average (mean +/- one SD = I +/-
      0; N=20). For the sexual cycle, the time of copulation between male and female
      ranged from 10 to 40 seconds (mean +/- one SD = 17.33 +/- 10.55, N=7). The
      spermatozoa are composed of a celular body and a flagellum, the size of the body
      is of 300 nm while the flagellum measures 1 700nm. The rods have a double
      membrane. Their mean length is almost 2.45 microm +/- 0.74, N=6; and their mean
      wide is 0.773 microm +/- 0.241, N=11. The evidence on the specific
      ultrastructural characteristics of the rotifer B. bidentatus is notorious, even
      more in the male and in the cyst cell. Regarding the ultrastructure of the
      spermatozoa and the rods, compared to other species they only differ in size,
      despite their structural resemblance. Our study of the ultraestructure of this
      species adds useful information that along with molecular data will help clarify
      the taxonomy of brachionid rotifers.

PMID- 24432531
TI  - [Spatio-temporal pattern of larvae and eggs of gastrointestinal nematodes in
      cattle pastures in Veracruz, Mexico].
AB  - The spatial and temporal distribution of gastrointestinal nematodes of cattle has
      been little studied in Mexico. Previous studies have described periods of higher
      larval presence, vertical and horizontal migration in grasslands, and the
      frequency of adult nematodes; as well as the effect of pasture trichomes on the
      migration and survival of Haemonchus larvae. The aim of this study was to
      determine the time-space layout and spread of gastrointestinal nematode larvae on
      pasture, and to estimate the effect of ivermectin applied to cattle on the time
      dependent abundance of their eggs in a ranch in Veracruz. To determine the spatio
      temporal arrangement, monthly morning grass samples were obtained from 30
      sampling points from July 2008 to June 2009. Third stage larvae (L3) from each
      point were counted, and aggregation patterns were estimated through variance/mean
      and negative binomial K indices. Additionally, the number of eggs per gram in
      cattle feces was determined, from samples with (CI) and without ivermectin (SI),
      using standard techniques. A total of 20 276 L(3) larvae were recovered in the
      pasture, of which an 80% corresponded to Haemonchus contortus. The highest
      nematode density with more than 5 000L(3)/kgDM was detected in October 2008, and
      the lowest in February and March 2009. The L3 showed an aggregated spatial
      pattern of varying intensity throughout the year. The number of eggs in the stool
      was not reduced with the ivermectin application to cattle, which suggested a
      failure of control. However, the highest parasite loads were observed from July
      to November 2008. We concluded that the application of ivermectin was not
      effective to control nematodes eggs, and that L3 populations fluctuated on
      pasture for ten months, providing an infection source to grazing animals
      afterwards.

PMID- 24432532
TI  - [Terrestrial gastropods from Misiones Province, Argentina].
AB  - The Atlantic Forest represents one of the global priority eco-regions for
      biodiversity conservation. In Argentina, this is represented by the Paranense
      Forest, which occupies much of the Misiones Province. In this paper, an updated
      list of land mollusks from Misiones Province is presented, and its species
      richness was evaluated comparing protected and unprotected areas. For this, we
      reviewed La Plata Museum Mollusk Collection, updated the literature review, and
      developed some field work between 2009 and 2010. For the areographic work, a grid
      (50 x 50 km) was applied to a Misiones province map. In this region, large areas
      of native vegetation constituting the Paranaense Forest still persist, and
      include protected areas such as the Iguazu National Park and Puerto Peninsula
      Provincial Park. These areas have been the most explored at the malacological
      level (both terrestrial and aquatic environments), a fact that is consistent with
      the greater number of records found, which may also be the explanation for the
      highest number of species recorded in the region. A database containing 497
      records was compiled. The number of species occurring in this Province was
      increased from 28 to 56; 11 of which were exotic species. A total of 38 of the
      species occurred in protected areas and 53 in unprotected areas; and 25 species
      were micro-mollusks. Orthalicidae was the family with the highest species number
      (10) and the widest distribution, occupying 16/20 sampling units. Megalobulimus
      was the genus found in a greater number of sampling units (14/20). The highest
      values of specific richness of land gastropods were found in Northern Misiones
      (R=32). This richness was similar to that previously reported for the Tucuman
      Province, although species occurring in both provinces were mostly different. The
      richness in Misiones Province border areas, as the Republic of Paraguay and the
      state of Santa Catarina (Brazil), was about twice that found in the province. The
      present study showed the existence of poorly explored areas at malacological
      level, especially in Central and Eastern Misiones. Data presented here will allow
      focus future sampling efforts on such areas, so patterns of species distribution
      can be better defined.

PMID- 24432533
TI  - [Structure and composition of terrestrial molluscs assemblages on the mogote
      vegetation complex of Escaleras de Jaruco, Cuba].
AB  - Cuba has one of the richest land snail faunas of the world. This important fact
      has promoted different kind of studies on this group to promote conservation
      programs, from which many studies have directed their efforts to inventories, and
      population and community ecology. To contribute with this population knowledge,
      we studied land snails assemblages in three karstic elevations at the "Escaleras
      de Jaruco-Tapaste-Cheche" Natural Protected Landscape, Mayabeque, Cuba. We aimed
      to analyze the variation of the composition and structure of the assemblages
      between the rainy and little rainy months. The study was conducted from August to
      November 2009 and from January to April, 2010, in ten permanent square plots (9
      m2) separated for over 20 m, on each elevation (Beluca, La Chirigota and La
      Jaula). In each plot, only live individuals were registered (physiologically
      active and at rest) to obtain species richness and abundance; besides,
      temperature (degree C) and relative humidity (%) were also considered in each
      plot. A total of 4248 individuals were observed which comprised two subclasses,
      five orders, 11 families, 20 genera and 21 species of terrestrial molluscs. From
      the total, 19 were Cuban endemics and eight were exclusive from Mayabeque,
      Matanzas. The Jaula showed the greater riches with 19 species, followed of Beluca
      with 17, and The Chirigota with 15. In the rainy months, La Jaula, showed
      individual's greater abundance with 1707, followed of Beluca with 1305 and La
      Chirigota with 1236. We observed differences in the population density in the
      three elevations between the rainy and little rainy months, which can be due to
      the climatic adverse conditions that are shown at the little rainy months.
      Additionally, during the survey we observed dominance of prosobranch species over
      the pulmonates. The specific abundance curves showed a steep slope, although was
      major in the rainy months in relation to the little rain months, which indicates
      the presence of dominant, common and rare species in the assemblages. In this
      study, it was demonstrated than the riches and the abundance of land snails in
      all three elevations, was favored for the elevated relative humidity and the air
      temperature during the rainy months. These environmental conditions resulted
      fundamental for the survival of these terrestrial gastropods, as the reproduction
      and search of food were favored.

PMID- 24432534
TI  - [Alpha and beta arthropods diversity from the different environments of Parque
      Nacional Los Cardones, Salta, Argentina].
AB  - The essential role of the National Parks is to protect nature, in order to
      prevent the deterioration and loss of the ecosystem under protection. Very few
      records about the diversity of arthropods are known from Los Cardones National
      Park, where three eco-regions are protected: Puna and Monte eco-regions and the
      High Andean Grassland of the Yungas. Here, we aimed to compare the alpha and beta
      diversity of arthropods in these eco-regions, and to prove if sites from the same
      ecoregion, show greater similarity between them in their assemblages, than with
      sites of the other eco-regions. We also identified arthropod orders with higher
      species richness, and indicated the families that contribute the most to the
      registered beta diversity. Three sampling sites were established on each eco
      region and the arthropods were sampled using pitfall traps and suction samples.
      We evaluated the obtained inventory through nonparametric estimators of species
      richness, and compared diversity among eco-regions through "diversity profiles"
      and "effective number of species". Beta diversity was assessed by different
      methods such as the Morisita Index, nonmetric multidimentional scaling analysis,
      a multiple permutation procedure, and a Similarity Percentage analysis. We
      recorded 469 spp/morphospecies and recognized three arthropod orders (spiders,
      dipterans and hymenopterans) that are diverse and abundant in the Park. Besides,
      the diversity in Los Cardones National Park was found to be high, but it was
      observed higher in the High Andean Grassland of the Yungas, and lower in the
      Puna. The inventory obtained was good, reached up to the 81% of the species
      richness estimated by nonparametric estimators. Each eco-region of the park
      showed a very particular arthropod community that was tested by a multi-response
      permutation procedure. The species turnover between eco-regions was high, so that
      the different environments of the protected area are contributing to the
      maintenance of the regional diversity of arthropods in the park. The assemblages
      of arthropods belonging to the same eco-region sites showed greater similarity
      among themselves than with those of more distant sites. This represents the first
      attempt for biodiversity studies in these areas, but more evaluations are
      required to detail on the possible climate change and human impacts in the
      ecosystem.

PMID- 24432536
TI  - Decadal increase in seagrass biomass and temperature at the CARICOMP site in
      Bocas del Toro, Panama.
AB  - The Caribbean Coastal Marine Productivity Program (CARICOMP) was launched in 1993
      to study regional long-term interactions between land and sea, taking
      standardized measurements of productivity and biomass of mangroves, coral reefs
      and seagrasses. Since 1999 continuous measurements of seagrass (Thalassia
      testudinum) parameters as well as environmental data have been recorded in
      Caribbean Panama. Replicate stations were selected near the Smithsonian Tropical
      Research Institute in Bocas del Toro. Sediment cores and quadrants were placed
      there to estimate biomass and productivity, respectively. Mean values for
      productivity, standing crop, turnover rate, total dry biomass, and Leaf Area
      Index were 1.74 gDW/m2/d, 66.6 gDW/m2, 2.62%/d, 1481 gDW/m2, and 4.65,
      respectively. Total dry biomass (shoots, rhizomes and roots) and LAI of T.
      testudinum increased significantly during the study period. Mean values for total
      rainfall, Secchi disk depth, sea surface temperature, and salinity were 3498 mm,
      8.24 m, 28.79 degrees C, and 32.26 psu, respectively. Sea surface temperature was
      the only environmental variable with a statistically significant change,
      increasing from 1999 to 2010. Correlation between sea surface temperature and 7
      testudinum parameters (total biomass and LAI) were both positive and significant.
      Human population has increased dramatically over the last ten years in Bocas del
      Toro region, increasing pressure (deforestation, runoff, wastewater) over coastal
      ecosystems (seagrasses, mangroves, coral reefs). Change in the abundance of 7
      testudinum may be linked to ocean warming, as a consequence to satisfy plant's
      metabolic requirements, although other local factors need to be analyzed (reduced
      grazing and increased eutrophication). A further warming of the ocean could have
      a negative effect on T. testudinum population, increasing respiratory demands and
      microbial metabolism.

PMID- 24432535
TI  - Population fluctuations of Pyrodinium bahamense and Ceratium furca (Dinophyceae)
      in Laguna Grande, Puerto Rico, and environmental variables associated during a
      three-year period.
AB  - Bioluminescent bays and lagoons are unique natural environments and popular
      tourist attractions. However, the bioluminescence in many of these water bodies
      has declined, principally due to anthropogenic activities. In the Caribbean, the
      bioluminescence in these bays and lagoons is mostly produced by the
      dinoflagellate Pyrodinium bahamense var. bahamense. Laguna Grande is one of the
      three year-round bioluminescent water bodies in Puerto Rico that are known to
      remain but P. bahamense var. bahamense density fluctuations have not been
      studied. In this study we describe water quality parameters and density
      fluctuations of the most common dinoflagellates in Laguna Grande, P. bahamense
      var. bahamense and Ceratium furca, over a three-year period. For this, three
      sampling stations were established in Laguna Grande from which water samples were
      collected in triplicate and analyzed for temperature, phosphates, nitrates,
      salinity, water transparency, fluorescence, and dinoflagellate densities, at the
      water surface and at 2m depth, from May 2003 to May 2006. The results showed a
      density fluctuation pattern for P. bahamense var. bahamense, where higher
      densities were observed mainly from April to September, and lower densities from
      October to February. Density fluctuations of C. furca were more erratic and a
      repetitive pattern was not observed. Densities of P. bahamense var. bahamense
      ranged from 0.48 to 90978 cells/L and densities of C. furca ranged from 0 to
      11,200 cells/L. The mean population density throughout the sampling period was
      significantly higher in P. bahamense var. bahamense (mean = 18,958.5 cells/L)
      than in C. furca (mean = 2601.9 cells/L). Population densities of P. bahamense
      var. bahamense were negatively correlated with C. furca densities during the
      first year of sampling; however, they were positively correlated during the third
      year. Non-significant differences between surface and 2m depth samples were
      observed for temperature, phosphates, nitrates, salinity, fluorescence, and
      densities of P. bahamense var. bahamense and C. furca, suggesting a vertically
      mixed water column. Water transparency was positively correlated with salinity
      and negatively correlated with fluorescence. Fluorescence was negatively
      correlated with salinity. The mean population densities of P. bahamense var.
      bahamense and C. furca observed in this study were within the range of previous
      reports in other bioluminescent water bodies in Puerto Rico and Florida, U.S.A.
      In order to conserve the continuous P. bahamense var. bahamense populations in
      Laguna Grande, as well as its bioluminescence, it is recommended to maintain the
      existing water flow levels in the 1.5 km long inlet/outlet channel; to maintain
      unpolluted water quality parameters within the bay, the hydrographical basin and
      adjacent waters, and to preserve mangrove communities within the basin and
      adjacent areas. Results of this study may help to develop management plans aiming
      to conserve P. bahamense, its bioluminescence and the lagoon attraction.

PMID- 24432537
TI  - Seasonal dynamics of phytoplankton in two tropical rivers of varying size and
      human impact in southeast Nigeria.
AB  - Phytoplankton occurrence and dynamics in rivers are mainly shaped by
      hydrophysical conditions and nutrient availability. Phytoplankton main
      structuring factors have been poorly studied in West African rivers, and this
      study was undertaken to identify these conditions in two tropical rivers that
      vary in size and human impact. For this, environmental variables and
      phytoplankton monthly samples were collected from the middle reaches of Asu and
      Cross rivers during an 18 months survey from March 2005-July 2006. Phytoplankton
      biomass (F=11.87, p=0.003), Shannon-Weiner diversity and species richness
      (F=5.93, p=0.003) showed significant seasonality in Asu but not in Cross River.
      Data was analyzed with Canonical correspondence analysis (CCA) and showed
      environmental differences between the two rivers, nitrate in Asu River (5.1-15.5
      mg/L) was significantly higher than Cross River (0.03-1.7 mg/L), while PO4 (0.2
      0.9 mg/L) was significantly lower in Asu River compared to Cross River (0.03-2.6
      mg/L) (p < 0.05). Eutrophic factors (NO1) determined primarily phytoplankton
      dynamics in Asu River, especially during the dry season, whereas hydrophysical
      factors (depth, transparency and temperature) shaped phytoplankton in Cross
      River. Taxa indicative of an eutrophic condition, such as Euglena, Chlorella,
      Chlorococcus, Ceratium, Peridinium, Anabaena, Aphanizomenon, Closterium,
      Scenedesmus and Pediastrum spp., were frequently encountered in the shallow
      impounded Asu River, while riverine species, such as Frustulia rhomboids,
      Gyrosigma sp., Opephora martyr and Surirella splendida dominated Cross River. A
      succession pattern was observed in the functional groups identified: Na/MP-->TB-
      >P (rainy-->dry season) was observed in Asu River, whereas MP/D predominated in
      Cross River for both seasons. We concluded that, if nutrients predominate
      hydrophysical factors in shaping phytoplankton during dry season (half of the
      year) then, they are as important as hydrophysical factors structuring
      phytoplankton during rainy season (the other half).

PMID- 24432538
TI  - [Comparative foliar anatomy and systematics of the Trichocentrum-clade with
      emphasis in Cohniella (Asparagales: Orchidaceae)].
AB  - The genera Cohniella, Lophiarella, Lophiaris, and Trichocentrum are included in
      the Trichocentrum-clade. These genera are distributed from Florida and Northern
      Mexico to Southern Brazil and Northern Argentina, growing in tropical deciduous
      forests or tropical rain forests and thorn scrub forests to pine-oak forest, from
      sea level to 1700 m. The leaf anatomical structure of 23 members of the
      Trichocentrum-clade was explored as a source of taxonomic and phylogenetic
      characters. A total of 11 species of Cohniella, three species of Lophiarella,
      seven species of Lophiaris, two species of Trichocentrum, and other four species
      were included as outgroup. Anatomical characters were studied by cross sections
      and paradermic observations of the middle portion of fresh leaves. Although
      anatomical characters were fairly homogeneous throughout the clade, twelve
      vegetative anatomical, phylogenetically informative characters were selected and
      coded for an analysis that was performed using an exhaustive search (implicit
      enumeration) implemented through TNT. The strict consensus of 2692 most
      parsimonious trees resulted in a poorly resolved polytomy, which however recovers
      the Trichocentrum-clade with a monophyletic, strongly supported Cohniella nested
      within it with unifacial leaves and the presence of cellular inclusions in the
      epidermis as synapomorphies. We concluded that the anatomy characters alone are
      insufficient to assess the relationships amongst the genera of the Trichocentrum
      clade. However, the two synapomorphies recovered for Cohniella strongly support
      its monophyly when these are analyzed in conjunction with other data sources
      (e.g., molecular and morphological characters).

PMID- 24432539
TI  - Acclimation of seedlings of Gnetum leyboldii Tul. (Gnetaceae) to light changes in
      a tropical rain forest.
AB  - The neotropical liana Gnetum leyboldii (Gnetaceae) is a gymnosperm that resembles
      angiosperms in wood anatomy, overall morphology, and seed dispersal mechanism.
      Like other woody lianas, seedlings germinate in the shaded forest understory and
      start climbing towards the canopy, being exposed to sites with extreme
      differences in light conditions. However, the extent of physiological and
      structural adjustment to contrasting light conditions in the early regeneration
      stages of Gnetum is unknown. To answer this question, we analyzed seedling growth
      and photosynthetic responses using a common garden experiment with two light
      regimes: full sun and low light (20% of full sun) at La Selva Biological Station,
      Costa Rica. We also characterized the germination pattern of this species. We
      monitored one and half-month old seedlings for four months. Leaf structure finely
      adapted to light treatments, but gas exchange properties were buffered by large
      seed reserves, which dominated biomass distribution (about 50% of the total
      biomass), followed by stem (27%), leaf (16%) and root biomass (6%) across light
      conditions. The presence of large seeds and the low photosynthetic rates of
      seedlings in both environments show that G. leyboldii is specialized to exploit
      deep shade. More research is needed to determine if the patterns found in G.
      leyboldii are typical of similar lianas that initially exploit deep-shaded
      understories in their accession to the canopy.

PMID- 24432540
TI  - [Palms conservation, patterns of use and diversity (Arecaceae) in rain forests
      from the Choco, Colombia].
AB  - Arecaceae is a family rich in species and provides resources for the subsistence
      of human groups in the tropical regions. The aim of this work was to assess the
      richness, diversity, composition, and use patterns of the family Arecaceae in
      three communities of the Medio Atrato, Choco, Colombia, in order to obtain useful
      information to support the sustainable use and conservation of this plant groups
      in the biogeographical area of the Colombian Choco. The fieldwork was carried out
      between 2009 and 2010 in the localities of Bete, Tangui and El Buey in the
      municipality of Medio Atrato. In each of the communities, a total of ten plots of
      80 x 5 m (400 m2; 0.4 ha per zone) were established and all individuals of palm
      species were counted and recorded. On the other hand, information on use types
      and useful organs was also recorded in each community through informal
      interviews. A total of 29 species and 18 genera were recorded. Bactris (24.13%)
      and Wettinia (10.34%) were the genera with most species richness. El Buey showed
      more species and genera richness (23 species, 17 genera) than Bete (15, 10) and
      Tangui (14, 11). The floristic similarity among the three communities was less
      than 45%. The species with higher use and ecological value were: Euterpe
      oleracea, Oenocarpus bataua, Attalea allennii, Manicaria saccifera, Bactris
      gassipaes and Wettinia quinaria. The categories of use with higher number of
      species and cultural importance were construction, food and handicraft. The most
      used structures of the palms were the stems and fruits. In conclusion, the
      results indicate that the Medio Atrato has high richness and diversity of palm
      species in a regional and national context. However, the relationship between
      number of use and ecological importance of the species depends on the locality
      and show that the socio-cultural significance of the palm species may vary among
      groups of people who share a same culture or biogeographic region. Future studies
      should be conducted to determine the role of the type of organ used as raw
      material on the demographic and ecological dynamic of the palm populations in the
      Choco and other Neotropical regions.

PMID- 24432541
TI  - Synchronism between Aspidosperma macrocarpon (Apocynaceae) resources allocation
      and the establishment of the gall inducer Pseudophacopteron sp. (Hemiptera:
      Psylloidea).
AB  - The joint interpretation of phenology and nutritional metabolism provides
      important data on plant tissues reactivity and the period of gall induction. A
      population of Aspidosperma macrocarpon (Apocynaceae) with leaf galls induced by a
      Pseudophacopteron sp. (Psylloidea) was studied in Goias state, Brazil. Assuming
      the morphological similarity between host leaves and intralaminar galls, a
      gradient from non-galled leaves towards galls should be generated, establishing a
      morpho-physiological continuum. The phenology, infestation of galls, and the
      carbohydrate and nitrogen contents were monthly evaluated in 10-20 individuals,
      from September 2009 to September 2010. Our objective was to analyze the
      nutritional status and the establishment of a physiological continuum between the
      galls and the non-galled leaves of A. macrocarpon. The period of leaf flushing
      coincided with the highest levels of nitrogen allocated to the new leaves, and to
      the lowest levels of carbohydrates. The nutrients were previously consumed by the
      growing leaves, by the time of gall induction. The levels of carbohydrates were
      higher in galls than in non-galled leaves in time-based analyses, which
      indicateed their potential sink functionality. The leaves were infested in
      October, galls developed along the year, and gall senescence took place from
      March to September, together with host leaves. This first senescent leaves caused
      insect mortality. The higher availability of nutrients at the moment of gall
      induction was demonstrated and seems to be important not only for the
      establishment of the galling insect but also for the responsiveness of the host
      plant tissues.

PMID- 24432542
TI  - Fast changes in seasonal forest communities due to soil moisture increase after
      damming.
AB  - Local changes caused by dams can have drastic consequences for ecosystems, not
      only because they change the water regime but also the modification on lakeshore
      areas. Thus, this work aimed to determine the changes in soil moisture after
      damming, to understand the consequences of this modification on the arboreal
      community of dry forests, some of the most endangered systems on the planet. We
      studied these changes in soil moisture and the arboreal community in three dry
      forests in the Araguari River Basin, after two dams construction in 2005 and
      2006, and the potential effects on these forests. For this, plots of 20 m x 10 m
      were distributed close to the impoundment margin and perpendicular to the dam
      margin in two deciduous dry forests and one semi-deciduous dry forest located in
      Southeastern Brazil, totaling 3.6 ha sampled. Besides, soil analysis were
      undertaken before and after impoundment at three different depths (0-10, 20-30
      and 40-50 cm). A tree (minimum DBH of 4.77 cm) community inventory was made
      before (TO) and at two (T2) and four (T4) years after damming. Annual dynamic
      rates of all communities were calculated, and statistical tests were used to
      determine changes in soil moisture and tree communities. The analyses confirmed
      soil moisture increases in all forests, especially during the dry season and at
      sites closer to the reservoir; besides, an increase in basal area due to the fast
      growth of many trees was observed. The highest turnover occurred in the first two
      years after impoundment, mainly due to the higher tree mortality especially of
      those closer to the dam margin. All forests showed reductions in dynamic rates
      for subsequent years (T2-T4), indicating that these forests tended to stabilize
      after a strong initial impact. The modifications were more extensive in the
      deciduous forests, probably because the dry period resulted more rigorous in
      these forests when compared to semideciduous forest. The new shorelines created
      by damming increased soil moisture in the dry season, making plant growth easier.
      We concluded that several changes occurred in the T0-T2 period and at 0-30 m to
      the impoundment, mainly for the deciduous forests, where this community turned
      into a "riparian-deciduous forest" with large basal area in these patches.
      However, unlike other transitory disturbances, damming is a permanent alteration
      and transforms the landscape to a different scenario, probably with major long
      term consequences for the environment.

PMID- 24432543
TI  - Assessment of genetic diversity in Brassica juncea (Brassicaceae) genotypes using
      phenotypic differences and SSR markers.
AB  - Brassica mustard species represent one of the most important oilseed crops in
      India, nevertheless, their genetic diversity is barely known. A better
      understanding on this topic is essential for the proper utilization of genotypes
      in breeding programmes. We evaluated the genetic diversity among 44 Indian
      mustard (Brassica juncea) genotypes including varieties/purelines from different
      agro-climatic zones of India and few exotic genotypes (Australia, Poland and
      China). For this, we used A and B genome specific SSR markers and phenotypic data
      on 12 yield and yield contributing traits. Out of the 143 primers tested, 134
      reported polymorphism and a total of 355 alleles were amplified. Dendrograms
      based on Jaccard's similarity coefficients and Manhattan dissimilarity
      coefficients were generated based on an average linkage algorithm (UPGMA) using
      marker data and phenotypic data. Genotypes were grouped into four clusters based
      on genetic distances. Both the clustering patterns based on Jaccard's similarity
      and Manhattan dissimilarity coefficients, independently, discriminated the
      genotypes effectively as per their pedigree and origin. PCoA revealed that, the
      grouping of genotypes based on SSR marker data is more convincing than phenotypic
      data, however, the correlation between phenotypic and genetic distance matrices
      was observed to be very low (r = 0.11). Hence, for diversity studies reliability
      on molecular markers is worth proving and SSR markers are the stronger tools than
      quantitative traits in discriminating B. juncea genotypes.

PMID- 24432544
TI  - Nesting ecology of Chelonia mydas (Testudines: Cheloniidae) on the Guanahacabibes
      Peninsula, Cuba.
AB  - The nesting colony of green sea turtles (Chelonia mydas) at Guanahacabibes
      Peninsula Biosphere Reserve and National Park is one of the largest in the Cuban
      archipelago; however, little information about its nesting ecology is available.
      Temporal and spatial variation in nesting and reproductive success as well as
      morphometric characteristics of gravid females were used to ecologically
      characterize this colony. Nine beaches of the Southernmost coast of
      Guanahacabibes Peninsula were monitored for 14 years (1998-2012) to determine
      green turtle nesting activity, from May to September (peak nesting season in this
      area). Beach dimensions were measured to determine nest density using the length
      and the area. Afterward the beaches were divided in two categories, index and
      secondary. Females were measured and tagged to compare new tagged females (823)
      with returning tagged females (140). Remigration interval was also determined.
      Temporal variation was identified as the annual number of nesting emergences and
      oviposits per female, with apparent peaks in reproductive activity on a biennial
      cycle in the first six years followed by periods of annual increase in nest
      number (2003-2008) and periods of decreasing number of nests (2010-2012). We also
      found intra-seasonal variation with the highest nesting activity in July,
      particularly in the second half of the month. The peak emergence time was 22:00
      02:00 hr. In terms of spatial variation, smaller beaches had the highest nest
      density and nesting was more frequent 6-9m from the high tide line, where
      hatchling production was maximized although hatchling success was high on
      average, above 80%. Morphometric analysis of females was made and newly tagged
      turtles were smaller on average than remigrants. Our results are only a first
      attempt at characterizing Guanahacabibes' populations but have great value for
      establishing conservation priorities within the context of national management
      plans, and for efficient monitoring and protection of nesting beaches.

PMID- 24432545
TI  - Population biology and diet of Pomadasys corvinaeformis (Perciformes:
      Pomadasyidae) in Caraguatatuba Bay, southeastern Brazil.
AB  - Pomadasys corvinaeformis inhabits sandy and rocky bottoms in coastal waters, and
      is common in trawl samples taken from beaches. The species is very abundant on
      the Brazilian coast, and is of high economic and ecological importance. This
      study examined the spatio-temporal distribution, population biology and diet of
      P. corvinaeformis in Southeastern Brazil. Samples were taken by trawling monthly
      from August 2003 to October 2004, in two previously selected areas. The Northern
      area is more exposed to wave activity and is influenced by a river, functioning
      as a small estuary. In contrast, the Southern area is relatively sheltered from
      wave energy and influenced to a lesser degree by smaller rivers. The length of
      the specimens was measured, and the sex and gonadal stage were macroscopically
      identified. The abundance of this species was compared between areas and among
      months. The diet was analyzed seasonally by the frequency of occurrence, the
      percent volume, and the index of alimentary importance. P. corvinaeformis
      occurred in unequal proportions in the two study areas (86% in the Northern area
      and 14% in the Southern area) and was found most abundant in May 2004, followed
      by June 2004. The proportion of mature and in-maturation individuals increased
      gradually from autumn to summer. Nine major groups of food items were recorded in
      the diet of P. corvinaeformis, and crustaceans comprised five of the categories:
      unidentified crustacean fragments, zoea larvae, amphipods, copepods and shrimps.
      In both, fish stomach and intestine, crustacean fragments were the most frequent
      item. The second most frequent items were shrimp in the stomach, and amphipods in
      the intestine (mainly represented by their tubes). These results demonstrate that
      P. corvinaeformis can be considered a carnivore, with a preference on benthic
      organisms.

PMID- 24432546
TI  - Age and growth in the indian major carp Labeo rohita (Cypriniformes: Cyprinidae)
      from tropical rivers of Ganga basin, India.
AB  - Labeo rohita is a member of the Indian major carp species and originally an
      inhabitant of the Ganga river network in India. It is among the top ten
      aquaculture species of the world. Since there is a lack of information on the
      growth pattern of the wild populations of this species, this study aimed at
      evaluating the pattern of age and growth, to support the development of effective
      management plans. A total of 1082 samples of L. rohita were obtained from May
      2009 to July 2012 in six drainages of the Ganga basin. Scales of the fish were
      used to determine the age and growth by analyzing the annual rings growth. Out of
      six populations, a maximum 8+ age classes were recorded from two rivers (Betwa
      and Sharda). The back-calculated lengths at 8+ age class ranged from 86.22 cm to
      91.66 cm. However, for the rest of rivers up to 7+ age classes were recorded.
      Among growth parameters, specific rate of length increase (C(l)) and specific
      rate of weight increase (Cw) showed decreasing trend, and three distinct life
      stages of L. rohita were recorded based on growth constant data (C(lt)). Analysis
      of variance (ANOVA) of the back-calculated length data set of six populations
      indicated a significant difference (p < 0.05). All three populations showed
      significant variation in length attainment during 1+ and 3+ age groups, while two
      populations showed significant variation in length attainment during the 2+ and
      7+ age classes. Additionally, analysis of age frequency at different length
      intervals indicated that with increase in age class, number of fish samples was
      reduced. Since the pattern of life history traits of L. rohita have not been
      attempted in the recent past; therefore, this study will guide fisheries
      biologists about the current stock structure of this fish across different
      spatial scale of the Ganga basin.

PMID- 24432547
TI  - The morphology and structure of the Hannibal Bank fisheries management zone,
      Pacific Panama using acoustic seabed mapping.
AB  - The Hannibal Bank sits within the Coiba UNESCO World Heritage Site in Pacific
      Panama and is also a fisheries management zone. Despite the protected status of
      the area and the importance of the Bank for commercial fish species such as
      snapper and tuna, the seamount has received no detailed survey except some
      collection of organisms. This study mapped the major topographic features and
      complexity of the Hannibal Bank seamount using acoustic remote sensing. A survey
      area of around 125 km2 was defined using existing charts and side-scan sonar data
      were collected during July 2008. A bathymetric output was imported to ArcGIS
      where a digital bathymetric model and slope map were created. The Benthic Terrain
      Modeler (BTM) extension for ArcGIS was used to calculate bathymetric position
      index and rugosity, and used to create a map of zones representing the various
      seabed morphology zones. The Hannibal bank is an elongated, triangular guyot
      (flat topped seamount), which ranges in depth from 53m to 416m, covers an area of
      76 km2 and is 14.4 km long and 7.1 km wide. Hannibal bank is composed of steep
      slopes, more gentle slopes, top of the seamount, crests (elevated ridges at the
      top of the pinnacles), rugose areas (on crests, top of seamount and slope),
      gullies and pinnacles. The bank is asymmetric in nature with the Northerly side
      having a relatively gentle slope with gullies across the surface compared to the
      SouthWest side which is far steeper and more rugose. There are two pinnacles to
      the North and South East of the bank that range in depth from 180 to 333 m. Rocky
      substrate makes up 22.6 km2 of the bank and sediment 37.8 km2. The bank and its
      steeply sided, rugose areas and pinnacles provide upright structures which can
      disrupt and topographically enhance currents, increasing productivity. The rugose
      areas of Hannibal Bank should be primary targets for further research efforts as
      they may contain corals and their rugosity indicates that these should be some of
      the highest faunal diversity areas of the bank. Hannibal Bank is likely to come
      increasing pressure in the future through climate change and fishing and this
      study has produced valuable information to assist in the future mapping and
      management of habitats, associated species and fisheries.

PMID- 24432548
TI  - [Fatty acids in different edible fish species from Mexico].
AB  - Different biotic and abiotic factors determine the fatty acid (FA) composition of
      fish tissues and organs. This information is useful for humans due to the fact
      that fish consumption is associated with health benefits. The aim of the present
      study was to identify the variation in the concentration of fatty acids,
      according to different factors, among ten edible marine fish species in Mexico,
      collected from June to December 2009 in the largest fish market in Mexico City:
      Euthynnus alletteratus, Sciaenops ocellatus, Bairdiella chrysoura, Sphyraena
      guachancho, Symphurus elongatus, Istiophorus platypterus, Ophichthus rex,
      Eugerres plumieri, Eucinostomus entomelas and Oreochromrnis mossambicus. Lipid
      content was gravimetrically quantified, the fatty acids were determined using a
      gas chromatograph and the results were statistically analyzed. Total lipid
      content ranged from 0.93 to 1.95 g/100 g in E. entomelas and O. urolepis
      hornorum, respectively. E. alletteratus, B. chrysoura, S. elongatus, I.
      platypterus, O. rex and E. plumieri presented the following order in FA
      concentration: Polyunsaturated FA (PUFA)>Saturated FA (SFA)>Monounsaturated FA
      (MUFA). S. ocellatus, S. guachancho and E. entomelas presented SFA>PUFA>MUFA; and
      only O. mossambicus presented SFA>MUFA>PUFA. O. mossambicus had the highest
      concentration (mg/100 g) of SFA (559.40) and MUFA (442.60), while B. chrysoura
      presented the highest content (mg/100 g) of PUFA (663.03), n-3 PUFA (514.03),
      EPA+DHA (506.10) and n-6 PUFA (145.80). Biotic and abiotic factors of the
      analyzed fish significantly influenced their FA concentration. Subtropical
      species presented 42.1% more EPA+DHA than tropical specie. Values presented here
      will vary according to the changes in the ecosystem and characteristics of each
      fish species, however the information generated in the present study is useful
      for improving fish consumption recommendations.

PMID- 24432549
TI  - ED-based screening programs for hepatitis C (HCV) highlight significant
      opportunity to identify patients, prevent downstream costs/complications.
AB  - New data suggest there is a huge opportunity for EDs to identify patients with
      the hepatitis C virus (HCV) and link them into care before downstream
      complications lead to higher medical costs and adverse outcomes. Early results
      from a pilot study at the University of Alabama Medical Center in Birmingham show
      that at least 12% of the targeted baby boomer population being screened for HCV
      in the ED is testing positive for HCV, with confirmatory tests showing that about
      9% of the screened population is infected with the disease. Both the Centers for
      Disease Control in Atlanta and the US Preventive Services Task Force recommend
      one-time HCV screening for patients who were born between 1945 and 1965. Public
      health experts say 75% of HCV infections occur in patients born during the baby
      boomer years, and that roughly half of them are unaware of their HCV status.
      Researchers at UAB report that so many patients are testing positive for HCV that
      demand for care can quickly overwhelm the health system if new primary
      care/specialty resources are not identified. Administrators of ED-based HCV
      screening programs in both Birmingham and Houston note that EDs with existing
      screening programs for HIV should have the easiest time implementing HCV
      screening. They also stress that patients are more accepting of HCV screening,
      and that the counseling process is easier.

PMID- 24432550
TI  - As the prescribing practices of emergency providers come under enhanced scrutiny,
      watch for red flags of drug-seeking behavior.
AB  - With deaths from opioid medication-related overdoses reaching epidemic
      proportions, researchers at two academic medical centers in Boston have
      identified key characteristics or red-flags that patients may be exhibiting drug
      seeking behavior. In a separate study, researchers note that the ED is a prime
      location for identifying and intervening with young people who are engaged in the
      non-medical use of opioid and sedative medications. Researchers have found that
      drug-seeking patients are more likely to request a narcotic by name, have
      multiple visits for the same complaint, report an allergy to non-narcotic drugs,
      have pain out of proportion to the exam, and visit the ED on weekends. When
      physicians compared their prescribing decisions based on their own impressions
      with data from a prescription drug monitoring program (PDMP), they changed their
      prescribing plan in 10% of cases. Physicians ended up writing more prescriptions
      for opioids once they had the PDMP data. Researchers at the University of
      Michigan in Ann Arbor found that one in 10 adolescents who presented to the ED
      between September 2010 and September 2011 reported that they engaged in non
      prescription opioid or sedative use within the previous year.

PMID- 24432551
TI  - Salaries are in a holding pattern, although upward pressure continues on
      compensation for ED medical directors.

PMID- 24432552
TI  - In review of ED utilization reduction strategies, data regarding impact on
      safety, outcomes in short supply.
AB  - To gather insight on an array strategies used to curb ED utilization,
      investigators conducted a systematic review of five types of interventions that
      are based outside of the ED: patient education, patient financial incentives, the
      creation of additional non-ED capacity, pre-hospital diversion, and managed care.
      While the available evidence showed that all of the interventions had some impact
      on reducing ED utilization, researchers caution that there was scant data showing
      what impact these interventions had on outcomes or safety. Investigators found
      that patient education interventions were associated with the greatest magnitude
      of reductions in ED use, but they stress that the interventions reviewed were
      very heterogeneous. Interventions involving patient financial incentives
      primarily focused on putting financial barriers in place between patients and the
      ED. They were effective at reducing ED utilization, but investigators caution
      that policy makers need to consider the potential impact on outcomes. There was
      some evidence that creating additional non-ED capacity fueled demand for care,
      but had a small impact on ED utilization. Going forward, emergency providers need
      to fully engage in any discussions about ED utilization and demonstrate the value
      that EDs bring to the health care system, say experts.

PMID- 24432553
TI  - [Spa types and antibiotic resistance of Staphylococcus aureus bloodstream
      isolates obtained form patients of the University Clinical Center in Gdansk].
AB  - INTRODUCTION: Staphylococcus aureus is a leading cause of bloodstream infections.
      For epidemiological investigations of this bacteria spa genotyping is used as the
      method which has a high discriminatory power and gives results that can be easily
      compared between laboratories. In contrast to methicillin-resistant S.aureus
      (MRSA), relatively little is known about spa types among methicillin-susceptible
      strains (MSSA). We used spa typing and antibiotic resistance patterns analysis
      for retrospective study of S.aureus bloodstream isolates population from the
      University Clinical Centre (UCC) in Gdansk. METHODS: The study was performed on
      53 isolates from patients of 19 different units/ departments of the UCC. The
      isolates were tested for the susceptibility to antimicrobial agents. Spa typing
      was performed on the basis of the sequence analysis of the polymorphic X region
      of the protein A gene (spa) amplified form the isolates. Spa types were
      determined by Ridom Staph Type software and were clustered into spa-CCs (clonal
      complexes) using the algorithm BURP-based upon repeat pattern. MLST (Multilocus
      Sequence Typing) clonal complexes were predicted from BURP analysis by the Ridom
      SpaServer database. In MRSA the staphylococcal chromosomal casette (SCC) mec was
      determined, RESULTS: Spa-typing yielded 26 types. Six spa-CC and seven singletons
      were identified. The most frequent was spa-CC021involving 38% of isolates. The
      CC021 consisted of 7 spa types and the most common was t021 corresponding with
      MLST-CC30. The second frequent was singleton, related to MLST-CC1, with only one
      type t127. There were 3 MRSA isolates in the population. The MRSA strains were
      identified as different spa types: t003/ SCCmecII, t008/SCCmecIV and clonally
      related to MSSA t032/SCCmecIV. No one MRSA strains belonged to spa-CC021.
      CONCLUSIONS: The spa clonal cluster corresponding with widely distributed among
      invasive S.aureus strains in Europe MLST-CC30 was found as the most frequent
      among S.aureus bloodstream isolates from the UCC. Occurrence of spa types which
      had a genetic background common to well known MRSA clonal lineages was observed.

PMID- 24432554
TI  - [Phenotypic evaluation of hydrophobicity and the ability to produce biofilm in
      coagulase-negative staphylococci isolated from infected very-low-birthweight
      newborns].
AB  - INTRODUCTION: Coagulase-negative staphylococci (CNS), particularly Staphylococcus
      epidermidis and Staphylococcus haemolyticus, are the leading cause of infection
      among infants with very low birth weight (<1500 g). The most important virulence
      factor of these pathogens is their ability to form biofilm. The aim of this study
      was to evaluate the surface properties, the ability to produce slime and biofilm
      formation of S. epidermidis and S. haemolyticus strains isolated from infections
      in very low birth weight neonates. METHODS: Isolates ofS. epidermidis (n=60) and
      S. haemolyticus (n=38) were obtained from neonates, hospitalized in two neonatal
      intensive care units in Poland. Cell surface hydrophobicity was determined by
      autoagglutination test (AA) in 0.9% NaCl and salt aggregation test (SAT) in
      ammonium sulphate solution. In order to determine the ability to produce slime,
      Christiensen's tube test with safranin staining and Congo Red Agar (CRA) test
      were carried out. The quantitative assessment of biofilm production was
      determined by crystal violet (CV) assay. RESULTS: Based on the AA test, it was
      demonstrated that almost all S. epidermidis and S. haemolyticus isolates showed
      no agglutination in sodium chloride saline. The SAT test indicated that the
      greatest number ofS. epidermidis isolates aggregated in concentration of 2 M,
      whereas, for S. haemolyticus, it was 0.5 M. In the Christiensen's method, the
      largest amount of the S. epidermidis isolates produced a small amount of slime
      (40%), whereas 68% of the S. haemolyticus isolates produced a large amount of
      slime. In CRA test, in both species, the most common result was the bacterial
      culture colour being almost black, which corresponds to low production of
      biofilm. Quantitative assessment of biofilm production in CV assay revealed that
      while 97% of the S. heamolyticus isolates produced high levels of biofilm,
      similar results were observed in only 43% of the S. epidermidis isolates.
      CONCLUSIONS: Based on the results obtained by phenotypic methods, it was
      demonstrated that the S. haemolyticus isolates showed a statistically significant
      stronger ability to produce mucus and form biofilm than the isolates ofS.
      epidermidis.

PMID- 24432555
TI  - [Detection of bordetella within the framework of the Eupert-labnet Bordetella PCR
      EQA].
AB  - INTRODUCTION: The aim of this study was evaluation of molecular identification
      results of samples including genomic DNA of Bordetella by using PCR method,
      obtained by laboratory of Department of Bacteriology NIZP-PZH and their
      comparison with the results obtained by other reference laboratories in EU. The
      study was conducted within the framework of the first external quality assessment
      (Eupert-labnet Bordetella PCR EQA). METHODS: The panel of ten coded samples of
      purified genomic DNA was investigated. The panel was designed to include dilution
      of genomic DNA from B. pertussis at the three concentrations 2 pg/microl (high),
      0,2 pg/microl (medium) and 0,02 pg/microl (low). The panel included as well DNA
      of other Bordetella species (B. parapertussis, B. holmesii, B. bronchiseptica)
      and H. influenzae at concentrations 2 pg/microl. There was also two ,,blank"
      samples containing only Tris Buffet (10mM, pH 8,0). Presence or absence of B.
      pertussis DNA in the tested samples was determined by using four PCR assays:
      conventional in-house PCR (detection of IS481 B. pertussis and IS1001 B.
      parapertussis), commercial multiplex PCR (detection of DNA B. pertussis),
      conventional in-hause real-time PCR (detection of IS481 B. pertussis) and
      commercial real-time PCR (detection of IS1001 B. parapertussis). RESULTS: All but
      one samples were correctly identified in our laboratory. Laboratory of Department
      of Bacteriology NIZP-PZH correctly detected DNA ofB. pertussis at both the
      ,,high" and ,,medium" dilution. In addition, the distinction between B. pertussis
      and other Bordetella species was correctly obtained by our laboratory. The
      negative samples, the two blank samples and one containing H. influenzae were
      correctly detected. CONCLUSIONS: Results of the first international external
      quality assessment have confirmed competences of laboratory of Department of
      Bacteriology NIZP-PZH in molecular identification of Bordetella pertussis.

PMID- 24432556
TI  - [Reproducibility of Fim2 and Fim3 antigens determination in Bordetella pertussis
      by serotyping method].
AB  - INTRODUCTION: Serotyping is a commonly used method to characterize the presence
      of Fimbriae 2 and 3 in Bordetella pertussis strains for epidemiological purposes
      and optimal choice of strain composition of the pertussis whole-cell vaccine.
      Monoclonal antisera against Fim2 and Fim3 are recommended to be used for
      microplate serotyping instead ofpolyclonal. Reliable evaluation offimbriae
      expressed by B. pertussis strains influence interpretation of vaccine-driven
      strain evolution. METHODS: To evaluate the impact of tests conditions on the
      reproducibility of serotyping, results of serotyping based on a standardized
      protocol for microplate agglutination with monoclonal antisera performed in three
      different accredited laboratories were compared. For the study isolates of three
      vaccine strains of B. pertussis deposited within seed lot system originating from
      different liofilization lots were compared. RESULTS: Lack of the complete
      agreement on serotyping results among three labs might relates to the differences
      of media used, subjective reading, test conditions, and specificity of the
      reagents. CONCLUSIONS: Serotyping results should be interpreted with caution and
      the type of media and culture conditions used should be precisely recommended
      after validation studies. Inconsistent results should be confirmed using an
      alternative technique, eg. ELISA or by reference laboratory.

PMID- 24432557
TI  - [Application of FilmArray assay for detection of respiratory tract infections in
      immunocompromised persons].
AB  - INTRODUCTION: A variety of viruses and bacteria are responsible for acute upper
      and lower respiratory tract infections worldwide. Severe and even fatal disease
      can occur especially in group ofimmunocompromised individuals. Accurate pathogen
      identification allows clinicians to determine the need for ancillary diagnostic
      testing, antibacterial and/or antiviral therapy and can motivate decisions
      regarding hospitalization and infection control measures. METHODS: We compared
      the diagnostic performance of FilmArray Respiratory Panel highly multiplexed
      nucleic acid amplification test with previous used direct immunofluorescence
      assay. Both assays were performed on a panel of 6 nasopharyngeal-secretion
      specimens and 6 BALF samples, collected from 12 patients, subjected to allogeneic
      haematological stem cells transplantation, with lower respiratory tract symptoms.
      RESULTS AND CONCLUSIONS: Among viruses detectable by both assays were especially
      influenzaA virus, parainfluenza viruses type 3 and respiratory syncytial virus.
      In conclusion, the FilmArray assay is rapid and extremely user-friendly system,
      with results available in just over one hour with almost no labor involved. In
      few laboratories its low throughput and qualitative results may be a disadvantage
      in some clinical settings.

PMID- 24432558
TI  - [Efficacy of taurine haloamines and chlorhexidine against selected oral
      microbiome species].
AB  - INTRODUCTION: Uncontrolled bacteria of dental plaque generate formation of oral
      biofilm located on teeth and subgingival surfaces. It may induce local
      inflammation (gingivitis) with further development of periodontal diseases. A
      variety of oral bacteria such as Streptococcus mutans and Porhyromonas gingivalis
      are involved in pathogenesis of dental carries and periodontitis. Very often
      bacterial infections are associated with candidiasis (Candida albicans).
      Chlorhexidine (CHX) is the most commonly used antiseptic in dentistry due to its
      strong antibacterial activity and capacity to reduce the accumulation of oral
      biofilms. However, other antiseptics, especially endodontic irrigants, are still
      tested to improve their preventive and therapeutic effects in oral cavity
      infections. In this in vitro study we have compared antimicrobial activity of CHX
      with that of taurine chloramine (TauC1) and taurine bromamine (TauBr), natural
      taurine derivatives with known antibacterial and anti-inflammatory properties.
      METHODS: Antimicrobial activity of CHX, TauC1 and TauBr was tested by incubation
      of the compounds with S. mutans, P gingivalis and C. albicans. The agents were
      incubated in low (105/ml) and high (108/ml) density microbe suspensions, related
      to early and late biofilm infections, respectively. In some experiments bacteria
      were incubated with a combination of CHX + NaOCl and CHX + TauBr. MIC was
      determined by the pour-plate method. RESULTS: CHX showed the strongest
      antimicrobial activity against all tested pathogens. On the contrary, TauC1 was
      the weakest antiseptics used without effect on the growth of C. albicans. TauBr
      at non-cytotoxic concentrations inhibited the growth of S. mutans and P
      gingivalis with slight effect on the low density C. albicans. All tested agents
      showed weaker antiseptic properties in the presence of serum. Moreover, we have
      shown that interactions between CHX and sodium hypochlorite (NaOC1), the main
      endodontic irrigant, but not between CHX and TauBr,resulted in precipitation.
      Therefore, it may restrict their simultaneous application in root canal
      treatment. However, in spite of this unwanted reaction, the mixture of CHX with
      NaOCl kills pathogens more effectively then CHX alone. CONCLUSIONS: The results
      confirmed CHX exceptional potential as primary antiseptic in dentistry,
      especially in prevention and treatment of dental carries, periodontal diseases
      and mouth candidiasis. Moreover, our study shows that TauBr may be used
      alternatively or in combination with CHX in killing of oral pathogens, due to its
      strong antibacterial and anti-inflammatory properties.

PMID- 24432559
TI  - [Evaluation of biocidal properties of silver nanoparticles against cariogenic
      bacteria].
AB  - INTRODUCTION: Antimicrobial properties of silver nanoparticles (SNP's) have been
      recentl well evaluated, and now are being considered as excellent candidates for
      therapeutic purposes. It is confirmed, that various solutions of colloidal SNP's
      possess significant antibacterial properties against such species as:
      Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas
      aeruginosa even at low concentrations, although there have been so far only a few
      researches evaluating antimicrobial activity of SNP's against cariogenic
      bacteria: Streptococcus mutans, Streptococcus salivarius and Streptococcus mitis
      responsible for initiation of dental carries. Tooth decay is infectious disease
      an worldwide, which may occur in patients of every age. Nanotechnology creates a
      new approach of designing of medical devices preventing or reducing bacterial
      colonization. METHODS: Colloidal silver solution (CSS) of concentration 350 ppm
      was used in this research. Nanoparticles size, shape and solution stability were
      evaluated. 16 strains of cariogenic bacteria, 4 isolates of each species: S.
      mutans, S. salivarius, S. sanguinis and S, mitis were obtained from plaque swabs
      of 7 patients treated for dental carries at Department of Conservative Dentistry,
      Medical University of Warsaw. MIC and MBC values for CSS's were evaluated.
      RESULTS: CSS used in this research is of good stability. No agglomeration or
      coalescence was observed during 24 hours of experiment. Silver nanoparticles were
      of round shape and had mean size of 67 nm. MIC values were: 12-25 ppm for S.
      salivarius, 25 ppm for S. sanguinis, 50-100 ppm for S. mitis and 50 ppm for S.
      mutans, while MBC values after 1 hour of bacterial contact with nanoparticles
      were 200-350 ppm for all cariogenic bacterial species. After 24 hours of contact
      MBC values were: 25-50 ppm for S. salivarius and S. sanguinis, 100-200 ppm for S.
      mitis and 200 ppmfor S. mutans. CONCLUSIONS: Antimicrobial properties of CSS
      depend on nanoparticles concentration and interaction time with bacteria. The
      susceptibility of cariogenic oral streptococci to silver nanoparticles is
      diversified. Sufficient concentration which inhibited all cariogenic bacteria in
      our research was 200 ppm after long (24 hours) period of silver nanoparticles
      interaction with bacteria.

PMID- 24432560
TI  - [Microbiological characteristics of selected liquid soaps for hands washing].
AB  - INTRODUCTION: According to common belief, supported by the authority of the World
      Health Organization - WHO, the common (social) hand washing is the simplest,
      cheapest and the most effective way of reduction the hospital-acquired
      infections. For this purpose products of"liquid soaps", present in a large number
      on the market, are most often applied. Microbiological status (microbiological
      purity and antimicrobial activity) of"liquid soaps" available on the Polish
      market is not known, because relevant routinely studies have not been performed.
      Only the antibacterial and / or antifungal activity of certain formulations is
      sometimes assessed, especially when the manufacturer suggests the standardized
      application of the products for surgical or hygienic procedures. The aim of this
      study was to determine the microbiological quality, especially microbiological
      purity and antimicrobial activity of the selected hands washing products,
      presents on the Polish market. METHODS: The 12 selected commercial products,
      available on the market in Poland, dedicated for hands washing were included into
      study. Microbiological purity test was carried out in accordance with the Polish
      Pharmacopoeia (FP) monograph (FP monograph numbers correspond to numbers of the
      European Pharmacopoeia monograph- Ph. Eur.) No 2.6.12 "Microbiological
      examination of non-sterile products: microbial enumaration tests", and the
      monograph of FP No. 2.6.13 "Microbiological examination of non-sterile products:
      test for specified microorganisms". The following physico-chemical properties of
      soaps were examined: the pH of the formulations was measured according to the
      monograph FP No. 2.2.3. "Potentiometric determination of pH", the density of
      products was assayed according to the monograph FPNo. 2.2.5. "Relative density"
      and determination the water activity was performed by monograph FP No 2.9.39
      "Water-solid interactions: determination of sorption-desorption isotherms and of
      water activity". Next, antibacterial and antifungal protection was determined in
      accordance with the monograph FP No 5.1.3. "Efficacy of antimicrobial
      preservation". The study of antimicrobial activity was carried out in accordance
      with PN-EN 1040 "Chemical disinfectants and antiseptics - Quantitative suspension
      test for the evaluation of basic bactericidal activity of chemical disinfectants
      and antiseptics - Test method and requirements (phase 1)". Finally, using the
      "time-kill" method the survival of microorganisms after different contact times
      of the products with bacteria and fungi were determined. RESULTS: All the
      examined products showed a very high microbiological purity. None of the
      formulations was characterized by a high acidity or alkalinity. All the analyzed
      products were slightly thicker than water, but such density of the preparation
      does not seem to be important parameter in the growth of microorganisms. The
      results of water activity estimation - the parameter indicating the presence of
      free, not chemically bound water stimulating microbes growth - do not show that
      low water content in the preparation may inhibit bacteria and fungi growth.
      Taking into consideration the antimicrobial protection of the products
      demonstrated in the tests carried out in accordance within FP monograph No 5.1.3.
      and PN-EN 1040, and analysing curves indicating killing rate of bacteria and
      fungi obtained by "time-kill" method, the microorganisms contaminating the
      products generally should not multiply in their environment, and gradually they
      die - what can take many hours or even days. CONCLUSIONS: The cases of bacterial
      infections connected with the usage of non-medical liguid soaps, applied in the
      health care units and described in the literature, should be considered as
      related rather to contamination of plastic packaging and dosage system, then to
      contamination of preparation itself inside the package. It was proved, that in
      all tested products amount of contaminating microbes diminishes in time. The
      dynamics of this process depends on the microorganisms character - bacteria dies
      quicker then fungi. The special attention should be given to washing, cleaning
      and disinfection of preparation dispensing systems, to avoid microbial
      contamination of product doses applied directly on the hands. It should be
      emphasized that only formulations containing antimicrobial agents in an
      appropriate amount, eliminate microorganisms from the skin surface fast and
      effectively. In case of hygienic and surgical procedures following the
      standardized manner in order to obtain required reduction rate of microorganisms
      in a short time - only products complying with appropriate EN standards are
      suitable. For these puroposes, the popular "liquid soaps" should not be used.

PMID- 24432561
TI  - [The influence of piracetam on behavior and brain receptors in C57BL/6 and BALB/c
      mice: nootropic and anxiolytic effects].
AB  - The influence of acute and long-term piracetam administration on the dynamics of
      rapid (non-specific, anxiolytic) and slow (specific, nootropic) behavioral drug
      effects, as well as on their interrelation with NMDA- and BDZ-receptors was
      studied in inbred mice strains differing in cognitive and emotional status-
      C57BL/6 and BALB/c. The BALB/c strain contained 17% less [3H]-flunitrazepam
      binding sites in frontal cortex and 22% less [3H]-MK801 binding sites in
      hippocampus as compared to those in C57BL/6 mice. Based on these data, BALB/c
      strain was used as a model of psychopathology, combining increased anxiety and
      cognitive deficit. Under the action of single, 7-fold, and 14-fold piracetam i.p.
      injections (200 mg/kg body weight, daily), a fast increase in NMDA-receptor
      density and slow escalation of the specific nootropic effect was observed in
      BALB/c mice. Non-specific anxiolytic effects in these mice increased for the
      first 1 - 7 days without any changes in BDZ-binding and then decreased to initial
      values accompanied by decrement of brain receptor concentration. Thus, in BALB/c
      mice, a slowly manifested specific nootropic action of piracetam develops,
      following an increase in NMDA receptor density, whereas the non-specific
      anxiolytic effect precedes the fast-paced changes in BDZ-binding site density.

PMID- 24432562
TI  - [Hypocoagulant effect of the novel dipeptide NGF mimetic GK-2].
AB  - The effect of an original dimeric dipeptide NGF mimetic, GK-2
      (hexamethylenediamide bis-N-monosuccinyl-L-glutamyl-L-lysine, designed on the
      basis of the beta-turn of the 4th NGF loop) on the hemostasis and fibrinolysis
      was studied in intact and diabetic Wistar rats in various periods of disorder
      development. Model diabetes was induced by single streptozotocin (40 mg/kg i.p.)
      administration. Blood glucose level, main parameters of thromboelastograms, and
      euglobulin clot lysis time were measured. The effect of GK-2 was studied under ex
      vivo conditions, by adding freshly prepared peptide solution to the blood plasma.
      The maximum increase in the thrombosis probability was observed in ten days after
      streptozotocin injection, as manifested by an increase in coagulation indices CI
      and I together with a decrease in the euglobulin clot lysis time. Adding GK-2
      (10(-5) M) to the blood plasma was found to normalize these parameters. The
      tendency to hypocoagulant effect was also observed in experiments with GK-2
      adding to the blood plasma of intact animals. The hypocoagulant effect of GK-2 in
      combination with its antihyperglycemic effect (revealed previously) is of great
      importance, since diabetes is known to be accompanied by violated
      microcirculation and increased risk of thrombosis.

PMID- 24432563
TI  - [Analgesic properties of morpholinoethylimidazobenzimidazole derivative RU-1205].
AB  - We have studied the analgesic activity of a morpholinoethylimidazobenzimidazole
      derivative (RU-1205) in comparison to butorphanol. It is established that the
      test compound exhibits a pronounced analgesic activity, which exceeded that
      ofbutorphanol six times in the hot-plate test and was comparable to the reference
      drug effect in the tail-flick and acetic acid-induced writhing tests. It is
      established that the analgesic action of RU-1205 is based on the kappa
      opioidergic mechanism.

PMID- 24432564
TI  - [Influence of the long-term administration of torasemide on morphometric
      characteristics of cardiac muscle under conditions of developed experimental
      postinfarction cardiosclerosis].
AB  - The possible antifibrotic effect of torasemide used for the treatment of model
      chronic heart failure (CHF) has been studied in rats aged 12 months with
      developed postinfarction cardiosclerosis (PICS). The antifibrotic effect was
      evaluated of the course of torasemide administration in a daily dose of 0.13
      mg/kg. A comparative analysis showed that torasemide did not affect the state of
      connective tissues in cardiac muscles of both intact rats and those with PICS. It
      was concluded that manifestations of the antifibrotic effect of torasemide can be
      related to the nosological form of CHF.

PMID- 24432565
TI  - [Metabolic effects of delta-sleep inducing peptide during physiological aging of
      the organism].
AB  - Subcutaneous injection of delta-sleep inducing peptide (DSIP) to postnatal rats
      (aged from 2 to 24 months) during 5 consecutive days every months at a dose of 10
      microg/100 g body weight favors normalization of the age-related changes in
      carbohydrate metabolism and shows hypoglycemic effect, as manifested by a
      decrease in the level of glycosylated hemoglobin in erythrocytes of test rats.
      The administration of DSIP in postnatal rats of different age also led to a
      decrease in serum total lipid level, total cholesterol level, and atherogenicity
      index and an increase in the level of high-density lipoprotein cholesterol.

PMID- 24432566
TI  - [Pharmacological activity of runihol and S-adenosyl-L-methionine in rats with
      experimental liver damage by reserve antituberculosis drugs].
AB  - The hepatoprotective action of runihol and S-adenosyl-L-methionine
      (ademethionine) has been studied in a group of 47 white outbred male rats with
      model liver injury induced by reserve antituberculosis drugs (PAS, prothionamide,
      cycloserine). The ability of test drugs to correct structural and functional
      liver disorders is established. Both runihol and ademethionine favored decrease
      in the signs of structural and functional liver disorders induced by reserve
      antituberculosis drugs, Showing mixed type of action, the test drugs promoted
      recovery of the liver parenchyma and reduced manifestations of hepatocyte
      dystrophy to the same extent, without manifestations of necrobiotic processes and
      a mononuclear infiltration.

PMID- 24432567
TI  - [Melatonin as a drug: present-day status and prospects].
AB  - Melatonin, which is produced by pineal gland and peripheral tissue cells, has a
      very wide spectrum of pharmacological activity. Available experimental data show
      that melatonin can provide universal protection of central nervous system and
      internal organs from damages. These properties can be successfully used in
      therapy of many diseases. However, for some reasons, the pharmacological activity
      of melatonin is not properly founded in clinical practice. Conditions for the
      discovery of therapeutic possibilities of melatonin are discussed, including
      prospects for its complex use in combination with traditional drugs.

PMID- 24432568
TI  - [Drug-induced liver damage and the problem of its pharmacological correction].
AB  - This review summarizes data on the pathogenesis and diagnostics of drug-induced
      liver damage. Special attention is paid to the role of individual genetically
      determined characteristics of drug metabolism in the development of this
      pathology. Results of experimental and clinical studies of the efficacy of
      hepatoprotectors in the treatment and prevention of the drug-induced
      hepatotoxicity are generalized.

PMID- 24432569
TI  - [About development of public health of the Russian Federation].
AB  - The article presents public health system characterized by public responsibility
      for health of citizen under various forms of property. The issues of management,
      planning, financing and organization of health care are discussed.

PMID- 24432570
TI  - [The comparative evaluation of tendencies in population mortality and particular
      characteristics of hospitalization under diseases of blood circulation system].
AB  - The analysis of data bases established that in the Russian Federation population
      mortality of diseases of blood circulation system in toto and of main diseases
      included in this class (100-199 of ICD-10) is significantly higher than in
      European countries. The population mortality is determined both by morbidity and
      quality of medical care in case of development of disease. In Russia, the
      increase of number of cases of hospitalization per one patient passed away due to
      these causes. This indicator was lower in comparison with corresponding
      indicators characterizing levels of hospitalization in EU countries. In Russia,
      to decrease mortality of this pathology it is needed to extend indications for
      hospitalization.

PMID- 24432571
TI  - [The epidemiological risk factors related to labor migration].
AB  - The prevention of diseases among migrants becomes a serious problem of public
      health of subjects of the Russian Federation. The system of public sanitary
      epidemiological inspection in the field of biological security of the Russian
      Federation demands a permanent enhancement.

PMID- 24432572
TI  - [The methods of prognostic evaluation of risk of child joining the dispensary
      group of frequently ill children].
AB  - The study was organized to develop the formalized diagnostic methods and computer
      program to evaluate the risk of child joining the dispensary group of frequently
      ill children. The sampling included 2742 children of different age groups. It is
      established that size of groups of frequently ill children consists 38.2% among
      children of preschool age, 32% among children of early school age and 21% among
      adolescents of senior school age. The risk factors of development of frequent
      respiratory diseases in child are revealed. The impact of these factors on the
      rate of respiratory diseases depending on the age of child is established. The
      methods and computer program are developed for prognostic evaluation of risk of
      child joining the dispensary group of frequently ill children according the
      results of analysis of hereditary factors, pathology of delivery and pregnancy,
      characteristics of breast feeding and conditions of life. The methods are
      approved during additional examination of 400 children of different age.

PMID- 24432573
TI  - [The opinion of mothers brining up disabled children about quality of medical
      care].
AB  - The article presents the results of questionnaire survey of mothers brining up
      disabled children aged from 1 to 4 years organized to evaluate respondents'
      satisfaction with delivered medical care and to establish mothers'awareness of
      disease of child. The results testify that alongside with applied measures
      directed to improve quality of medical care the activities are needed to be
      applied to parents to increase their awareness of child health condition, causes
      of development of disease and characteristics of its course, methods and
      perspectives of treatment and prognosis of disease.

PMID- 24432574
TI  - [The impact of public health system on mortality of malignant neoplasms in
      Voronezh oblast].
AB  - The total mortality and population mortality of main classes of diseases and
      single causes of death are to be considered in operative and strategic planning
      of development of national economy and industry In the Russian Federation, the
      decrease of mortality of neoplasms including malignant ones up to 190 per 100 000
      of population in 2020 will be one of indicators of effectiveness of
      implementation of the State program of development of public health in the
      Russian Federation. The study was organized to determine the possibility to
      impact the level and dynamics of mortality of malignant neoplasms by means of
      variation of managed factors on the basis of indicators of activity of public
      health system. The main indicators of population health and activity of health
      institutions of Voronezh oblast were analyzed. The methods of mathematical
      statistics, management theory, system analysis and mathematical modeling were
      applied. To study the impact of managed factors on mortality of malignant
      neoplasms on the territory of Voronezh oblast the analysis of correlation
      interdependency was applied concerning 162 factors characterizing condition and
      activity of public health system according oblast districts and level of
      mortality of malignant neoplasms among adult population. The combinations of
      factors were calculated using the model to determine the level of prospective
      mortality to come in certain time after implementation of activities changing the
      given levels of factors. The data concerning qualitative interrelationship of
      indicators of condition and functioning of network of health institutions with
      indicators of level and dynamics of mortality of malignant neoplasms can be
      applied to model and forecast and to evaluate the current and forthcoming
      situation according indicators of mentioned mortality on the territory of
      Voronezh oblast in development of comprehensive plan of activities targeted to
      decreasing of this indicator.

PMID- 24432575
TI  - [The characteristics of motivation to follow healthy life-style].
AB  - The article specifies the notion of motivation to healthy life-style. The main
      factors developing this motivation are considered. The personal proposal of
      classification of motives to develop healthy life-style is presented.

PMID- 24432576
TI  - [The characteristics of population health in social ecological conditions of the
      Primorskii Krai].
AB  - The article presents the results of sociological survey of residents of different
      bioclimatic zones of urbanized and rural territories of different bioclimatic
      zones of the Primorsky Kraiy in municipalities with different demographic,
      ecological and social characteristics. The analysis of survey data using the
      technique of P.V. Terentiyev correlation pleiades was applied. The relationship
      was established between a number of such factors as social industrial
      environment, ecological condition of territory of residence, life-style and
      climate with population health.

PMID- 24432577
TI  - [The analysis of infant mortality in Omsk oblast' in 2002-2012].
AB  - In Omsk oblast during 2002-2012 a stable increase of birth rate is noted. Against
      the background of birth rate increase up to 2011 a positive dynamics of decrease
      of infant mortality was noted. In 2012, indicator of infant mortality increased
      up to 38.9% as compared with 2011. This occurrence can be explained by the change
      over to the new criteria of viviparity from January 1 2012. No significant
      alterations occurred in the structure of infant mortality in 2002-2012.

PMID- 24432578
TI  - [The level and dynamics of social adaptation of patients with disorders of
      schizophrenic specter].
AB  - The article considers the results of study of alteration of level of social
      adaptation of patients with schizophrenia and disorders of schizophrenic specter
      in the process of application of curative rehabilitative activities in
      psychiatric hospital considering the effect of gender factor. Depending on the
      clinical social characteristics four groups of patients are singled out: patients
      with primary hospitalizations in psychiatric hospital, patients with repeated
      hospitalizations during a year, patients on compulsory treatment and patients
      with continuous hospitalization more than a year In various groups of patients
      the different effect of gender factor is established both on initial level of
      indicators of social adaptation and on alterations of indicators during treatment
      process.

PMID- 24432579
TI  - [On the optimization of diagnostic of functional conditions of students of
      sportizated comprehensive secondary school].
AB  - In the modern school education an increase of pedagogic innovations is noted. One
      of these innovations is the sportization of physical culture education of
      students of comprehensive secondary schools. Thereupon, a need occurs to
      implement an individual approach to selection of physical loads for children of
      school age considering gender aspect. The study was organized to substantiate the
      effectiveness of educational training classes in sportizated comprehensive
      secondary schools considering individual characteristics of degree of tension of
      regulatory systems in senior students. The method of mathematical analysis of
      cardiac rhythm under orthostasis was applied. The recommendations are developed
      for trainers-teachers of comprehensive secondary schools concerning the dosage of
      physical loads depending on type of sports. The analysis of experimental data
      revealed effectiveness of educational training classes considering individual
      characteristics of physical conditions of senior students.

PMID- 24432580
TI  - [The methodic approaches to calculation of potential relevance of clinical
      diagnostic technologies].
AB  - The article presents the calculation of potential relevance of clinical
      diagnostic technologies for population of Novosibirsk oblast relating to leading
      nosology forms of diseases on the basis of the results of diagnostic of
      population pathology using different techniques in the regional diagnostic
      center.

PMID- 24432581
TI  - [The expertise evaluation of organization of rendering of acute, emergency and
      urgent medical care in rural regions of Novosibirsk oblast'].
AB  - The most problematic spheres in the resource support of emergency medical care to
      rural residents are the completeness of staff of physicians in rural medical
      surgeries, community hospitals and departments of emergency medical care in
      central district hospitals. The provision of feldsher obstetrics posts with
      sanitary motor transport and medical equipment is yet another problematic sphere.
      The main troubles during provision of emergency medical care at feldsher
      obstetrics posts are related to surgery treatment. The organization of emergency
      and urgent medical care suffers of many unresolved problems related to
      informational program support at feldsher obstetrics posts, polyclinics of
      central district hospitals.

PMID- 24432582
TI  - [The system of medical care support of patients with acute disorders of cerebral
      circulation].
AB  - The article considers actual issues of organization of medical care support of
      patients with acute disorders of cerebral circulation based on implementation of
      innovative medical and organizational technologies in the Republic of Kazakhstan.

PMID- 24432583
TI  - [The becoming of public medicine in the second half of XVIII--first half of XIX
      centuries: report. V. The main results of implementation of concept of medical
      police].
AB  - The article considers the main political, social, economic and scientific
      aftermath of practical realization of concept of medical police in late XVIII-
      seventieth years of XIX centuries. The issues of cardinal reformation of hygiene
      and its selection as an independent scientific discipline are analyzed in detail.
      The issues related to becoming of epidemiology are discussed too.

PMID- 24432584
TI  - [The becoming of medical care to workers in the north-Eastern Caucasus in second
      half of XIX--early XX centuries].
AB  - The article considers the issues of becoming of medical care to workers of
      industrial enterprises, oil-extracting enterprises, fishery, construction and
      maintenance of the Vladikavkaz railroad in the north-Eastern area of Caucasus.
      The information is presented concerning first curative institutions supporting
      local workers.

PMID- 24432585
TI  - [About the clinical school of D.D. Pletnev: Professor B.A. Egorov (1889-1963)].
AB  - The article considers the issues of clinical school created in the first half of
      XX century by D.D. Pletniyev, one of the founders of therapy in the USSR. The
      article for the first time presents the scientific biography and complicated
      course of life of B.A. Yegorov, one of the leading representatives of this
      school.

PMID- 24432586
TI  - Popular science.

PMID- 24432587
TI  - Combination microwave ovens: an innovative design strategy.
AB  - Reducing the sensitivity of microwave oven heating and cooking performance to
      load volume, load placement and load properties has been a long-standing
      challenge for microwave and microwave-convection oven designers. Conventional
      design problem and solution methods are reviewed to provide greater insight into
      the challenge and optimum operation of a microwave oven after which a new
      strategy is introduced. In this methodology, a special load isolating and energy
      modulating device called a transducer-exciter is used containing an iris, a
      launch box, a phase, amplitude and frequency modulator and a coupling plate
      designed to provide spatially distributed coupling to the oven. This system, when
      applied to a combined microwave-convection oven, gives astounding performance
      improvements to all kinds of baked and roasted foods including sensitive items
      such as cakes and pastries, with the only compromise being a reasonable reduction
      in the maximum available microwave power. Large and small metal utensils can be
      used in the oven with minimal or no performance penalty on energy uniformity and
      cooking results. Cooking times are greatly reduced from those in conventional
      ovens while maintaining excellent cooking performance.

PMID- 24432588
TI  - Optimization of hydrous ferrous sulfate dehydration by microwave heating using
      response surface methodology.
AB  - The work relates to assessing the ability of the microwave for dehydration of
      large amount of waste hydrous ferrous sulfate generated from the titanium pigment
      process industry. The popular process optimization tool of response surface
      methodology with central composite design was adopted to estimate the effect of
      dehydration. The process variables were chosen to be power input, duration of
      heating and the bed thickness, while the response variable being the weight loss.
      An increase in all the three process variables were found to significantly
      increase the weight loss, while the effect of interaction among the parameters
      were found to be insignificant. The optimized process conditions that contribute
      to the maximum weight loss were identified to be a power input of 960 W, duration
      of heating of 14 min and bed thickness of 5 cm, resulting in a weight loss of
      31.44%. The validity of the optimization process was tested with the repeat runs
      at optimized conditions.

PMID- 24432589
TI  - Unusual effect of the magnetic field component of the microwave radiation on
      aqueous electrolyte solutions.
AB  - The heating characteristics of aqueous electrolyte solutions (NaCl, KCl, CaCl2,
      NaBF4, and NaBr) of varying concentrations in ultrapure water by 2.45 GHz
      microwave radiation from a single-mode resonance microwave device and a
      semiconductor microwave generator were examined under conditions where the
      electric field (E-field) was dominant and where the magnetic field (H-field)
      dominated. Although magnetic field heating is not generally used in microwave
      chemistry, the electrolyte solutions were heated almost entirely by the
      microwaves' H-field. The heating rates under H-field irradiation at the higher
      concentrations of electrolytes (0.125 M to 0.50 M) exceeded the rates under E
      field irradiation. This inversion phenomenon in heating is described in terms of
      the penetration depth of the microwaves. On the other hand, the action of the
      microwave radiation on ethylene glycol containing an electrolyte differed from
      that observed for water under E-field and H-field conditions.

PMID- 24432590
TI  - Assessment of heating rate and non-uniform heating in domestic microwave ovens.
AB  - Due to the inherent nature of standing wave patterns of microwaves inside a
      domestic microwave oven cavity and varying dielectric properties of different
      food components, microwave heating produces non-uniform distribution of energy
      inside the food. Non-uniform heating is a major food safety concern in not-ready
      to-eat (NRTE) microwaveable foods. In this study, we present a method for
      assessing heating rate and non-uniform heating in domestic microwave ovens. In
      this study a custom designed container was used to assess heating rate and non
      uniform heating of a range of microwave ovens using a hedgehog of 30 T-type
      thermocouples. The mean and standard deviation of heating rate along the radial
      distance and sector of the container were measured and analyzed. The effect of
      the location of rings and sectors was analyzed using ANOVA to identify the best
      location for placing food on the turntable. The study suggested that the best
      location to place food in a microwave oven is not at the center but near the edge
      of the turntable assuming uniform heating is desired. The effect of rated power
      and cavity size on heating rate and non-uniform heating was also studied for a
      range of microwave ovens. As the rated power and cavity size increases, heating
      rate increases while non-uniform heating decreases. Sectors in the container also
      influenced heating rate (p < 0.0001), even though it did not have clear trend on
      heating rate. In general, sectors close to the magnetron tend to heat slightly
      faster than sectors away from the magnetron. However, the variation in heating
      rate among sectors was only 2 degrees C/min and considered not practically
      important. Overall heating performance such as mean heating rate and non-uniform
      heating did not significantly vary between the two replications that were
      performed 4 h apart. However, microwave ovens were inconsistent in producing the
      same heating patterns between the two replications that were performed 4 h apart.

PMID- 24432591
TI  - Migrating temperature "thermo-chromatographic" pulses (TCP) initiated by radio
      frequency (RF) heating.
AB  - In the present study, the astonishing influence of water dosage on a purged dry
      packed bed of NaY zeolite in the presence of an electric field with a frequency
      of 13.56 MHz was investigated. The injection of a small amount of water to the
      inlet of the bed led to pronounced selective heating of the inlet zone by more
      than 150 K. Thus, water represented a very effective coupling medium for
      dielectric heating. The selectively heated zone then slowly moved through the
      whole packed bed and a water pulse finally left the zeolite. This effect
      correlated with a coupled water and heat flux was called thermo-chromatographic
      pulse (TCP) emphasizing its analogy to chromatography. The phenomenon could not
      be performed by using conventional (convective) or microwave heating. It was
      demonstrated under various conditions and explained by a new model based on own
      experimental results as well as data from literature. The model will be the
      objective of a forthcoming publication.

PMID- 24432592
TI  - [The relevance and prospects of introducing a uniform federal register of
      patients with viral hepatitis B and C in Russia].
AB  - The article provides the current epidemiological characteristics of viral
      hepatitis B and C and the existing problems of registering parenteral viral
      hepatitides in Russia. It justifies the need for introducing a uniform federal
      registry of patients with viral hepatitis B and C and shows prospects for its
      introduction.

PMID- 24432593
TI  - [The HIV infection situation in the Russian Federation].
AB  - AIM: To evaluate current trends in the development of an epidemic process of HIV
      infection in Russia. MATERIALS AND METHODS: Case report forms entering the
      Federal Research Methodology Center for AIDS Prevention and Control of the
      Central Research Institute of Epidemiology, Russian Inspectorate for the
      Protection of Consumer Rights and Human Welfare, were analyzed. RESULTS: In
      Russia, the HIV epidemic is on the rise; both the absolute number of people with
      HIV infection and its rate in the population are increasing. Compared with 2000,
      there is a shift of the epidemic to older age groups (30-40 years); there are
      increases in the proportion of women among new HIV-infected cases and in the
      number of babies born to HIV-positive mothers. Injection drug use remains a major
      risk factor for HIV transmission; the number of people infected through
      heterosexual intercourse continues to rise every year. CONCLUSION: The main
      reason for a more widespread HIV epidemic is the very low coverage of both
      vulnerable groups and the general population with prevention programs.

PMID- 24432594
TI  - [Experience with Invirase as part of triple therapy as the drug of choice in the
      perinatal prevention of HIV transmission in the Ul'ianovsk Region].
AB  - AIM: To retrospectively analyze the efficacy and safety of ritonavir-boosted
      saquinavir (SQV) in the perinatal prevention of HIV infection in pregnant women
      in the Ulyanovsk Region. MATERIALS AND METHODS: The outpatient cards of HIV
      positive pregnant women who received ritonavir-boosted SQV in a dose of 1000/100
      mg bid in combination with zidovudine or stavudine and lamivudine for the
      perinatal prevention of HIV infection in 2010-2011 were retrospectively analyzed.
      The main efficiency criterion was a proportion of children taken off a regular
      medical check-up in terms of perinatal contact as healthy at 18 months post
      birth. The additional criteria (end points) were changes in viral load and CD4
      cell count at 4 and 8-12 weeks after initiation of prevention. RESULTS: The
      analysis included data on 98 HIV-positive pregnant women. The history of HIV
      infection was 3 years or less in 63.2% of the patients. Stage 3 and 4A HIV
      infection was stated in 87 and 13% of the women, respectively. Treatment with
      ritonavir-boosted SQV + 2 nucleotide reverse transcriptase inhibitors was started
      in 84.8% of the women at 15-28 weeks' gestation and in 12.2% of cases in earlier
      periods. Four weeks after initiation of highly active antiretroviral therapy, the
      viral load showed a 1-4 log10 decrease. By that time and at 8-12 weeks, it was
      undetectable (< 500 copies/ml) in 75 (76.5%) and 82 (83.6%) women, respectively.
      With a decrease in the viral load, CD4 cell count increased by 100-500 per mm3
      (mean 160 per mm3). The efficiency of prevention of perinatal HIV transmission
      was 100%. No serious adverse events were observed. CONCLUSION: The use of
      ritonavir-boosted SQV in combination with two nucleotide reverse transcriptase
      inhibitors is an effective and safe chemoprevention regimen for perinatal HIV
      transmission in pregnant women.

PMID- 24432595
TI  - [The application of decision trees for constructing an algorithm for the
      differential diagnosis of zoonotic infections].
AB  - AIM: To attempt to construct an algorithm using the routine epidemiological,
      clinical and laboratory data for the differential diagnosis of ixodid tick-borne
      borreliosis (ITBB) caused by Borrelia miyamotoi (BM-ITBB) and other zoonotic
      infections that are endemic in Russia. SUBJECTS AND METHODS: The investigation
      enrolled the adult patients treated at the Republican Hospital for Infectious
      Diseases (Izhevsk) in 2010-2012 with diagnoses of BM-ITBB (n = 71), Lyme disease
      (n = 38), tick-borne encephalitis (TBE) (n = 25), and hemorrhagic fever with
      renal syndrome (n = 27). The Decision Tree procedure in IBM SPSS Statistics was
      used to analyze more than 65 variables characterizing a disease case. RESULTS:
      The final decision tree had 7 dichotomous fissions in accordance with the values
      of several indices (presence of erythema migrans, tick bite, goat's milk
      consumption, sweating, vertigo, nausea, abdominal pain, as well as blood
      concentrations of platelets, alanine aminotransferase, and count, and urea) and
      formed 8 terminal nodes. The proposed algorithm provides correct classification
      in 95% of disease cases. CONCLUSION: ITBB caused by B. miyamotoi can be
      successfully discriminated from other widespread zoonotic infections. Thus,
      practitioners have an additional opportunity to detect and diagnose the "new"
      infection BM-ITBB.

PMID- 24432596
TI  - [Current principles in the chemoprophylaxis of acute respiratory viral
      infections].
AB  - AIM: To evaluate the preventive efficacy of the Russian antiviral drug ingavirin
      (vitaglutam) in the epidemiological foci with the peak incidence of acute
      respiratory viral infections (ARVI). SUBJECTS AND METHODS: Four hundred men and
      women aged 18 to 65 years from the epidemic foci of ARVI who had been in close
      daily contact with the patients whose diagnosis was verified by laboratory tests
      were examined. Two hundred persons received prophylaxis with ingavirin (a 90-mg
      oral capsule once daily for 7 days) and 200 took placebo according to the same
      scheme. The efficiency index and coefficient were calculated and the relative
      risk of the disease was estimated to evaluate the efficiency of ARVI prevention.
      A pharmacoeconomic analysis was made. RESULTS: There is evidence that the
      administration of 90-mg ingavirin capsules (OAO "Valenta Farm", Russia) caused a
      reduction in morbidity rates among those who had been in contact by 63% and in
      the risk of ARVI by 2.7 times. There was a reduction in the duration of fever by
      one day and a milder course of respiratory disease in the ingavirin-treated
      contact persons who developed ARVI. CONCLUSION: Ingavirin meets all requirements
      for current drugs for the nonspecific prevention of ARVI at the peak of its
      incidence. It has a pronounced protective effect and broad-spectrum activity, low
      toxicity and high safety, which allows it to be recommended for the emergency
      intrafocal prevention at the peak of the incidence of influenza and ARVI in
      adults.

PMID- 24432597
TI  - [C-reactive protein as a marker of the severity of an infectious process in acute
      myeloid leukemia patients with neutropenia].
AB  - AIM: To determine C-reactive protein (CRP) levels as diagnostic markers of
      infection in acute myeloid leukemia (AML) patients with neutropenia. SUBJECTS AND
      METHODS: Sixty-three AML patients (28 men and 35 women) aged 20 to 77 years
      (median 50 years) were examined. According to the French-American-British (FAB)
      classification, the types of AML were as follows: M0 (n = 3), M1 (n = 9), M2 (n =
      35), M4 (n = 10), and M5 (n = 6). All the patients had chemotherapy-associated
      neutropenia (granulocytes, less than 0.5.10(9)/l). In different treatment steps,
      all the patients developed infectious complications (the study analyzed the data
      of 86 cases). RESULTS: In patients with localized infections (such as mucositis,
      abscess, pneumonia, etc.) or fever of unknown origin (FUO), the levels of CRP
      were not statistically significant different, but were significantly higher than
      in those without infectious complications. The concentrations of CRP did not
      differ in patients with systemic inflammatory response syndrome (SIRS) and in
      those with sepsis. At the same time, the level of CRP in systemic infection
      (SIRS, sepsis) was significantly higher than that in localized infection (p <
      0.001). In patients with neutropenia, the median CRP levels were as follows: 7
      mg/l (range 0-37; 95% reference interval (RI) 0 to 32) for those without
      infection 56 mg/l (range 13-104; 95% RI 17 to 104) for those with localized
      infection or FUO; and 168 mg/l (range 103-399; 95% RI 105 to 362) for those with
      systemic infection. CONCLUSION: CRP is a marker of the severity of an infectious
      process in AML patients with neutropenia. The increase of its level more than 32
      mg/l serves a valid criterion for the presence of infection and more than 105
      mg/l does for that of a systemic inflammatory response in these patients.

PMID- 24432598
TI  - [Cryptococcosis in hematology practice].
AB  - AIM: To study the clinical manifestations of cryptococcosis, its diagnostic
      features, and treatment results in patients with hemoblastoses. SUBJECTS AND
      METHODS: The study included adult patients with cryptococcosis treated at the
      Hematology Research Center (HRC) in 2005 to 2011. The diagnosis of cryptococcosis
      was established on the basis of isolation of Cryptococcus neoformans from a blood
      culture or determination of positive cryptococcal antigen in the cerebrospinal
      fluid (CSF) of patients with infection symptoms. RESULTS: During 7 years, 19
      patients aged 19 to 68 years (median 47 years) were diagnosed as having
      cryptococcosis. In the pattern of cryptococcosis, there was a preponderance of
      patients with lymphoma (31%) and those with acute lymphoblastic leukemia (26%) at
      the stages of hemoblastosis remission induction (32%) and consolidation (26%).
      The diagnosis was made in 9 (47%) patients at the Intensive Care Department, HRC.
      The major risk factors of cryptococcosis were previous cytostatic drug exposure
      (68%), use of immunosuppressive and glucocorticoid drugs (63%), and
      granulocytopenia (42%). Seventeen (78%) patients were diagnosed with cryptococcal
      meningitis or meningoencephalitis; 1 patient had cryptococcal sepsis and 1
      patient had possible cryptococcal pneumonia. All the patients were given
      antifungal agents. Amphotericin B, fluconazole, and a combination of antimycotics
      were used as first-line drugs in 16 (84%), 1 (5.5%), and 2 (10.5%), respectively.
      When their health became better, the patients were treated with voriconazole or
      fluconazole. Within 30 days after the diagnosis of cryptococcosis, 5 (26%)
      patients died; of them 2 had tumor progression concurrent with infection.
      CONCLUSION: In cryptococcosis, the central nervous system is predominantly
      involved in the infectious process. The determination of cryptococcal antigen in
      CSF is a necessary diagnostic component in meningitis and meningoencephalitis in
      patients with blood system tumors, lymphatic ones in particular. When
      cryptococcosis is timely diagnosed and treated, its mortality, when the tumor is
      controlled, is lower than that in other invasive mycoses.

PMID- 24432599
TI  - [Results of treatment for candidemia in patients with blood system tumors].
AB  - AIM: To study the etiology, clinical manifestations, risk factors, and results of
      treatment for candidemia (CE) in patients with blood system tumors. SUBJECTS AND
      METHODS: The investigation included the patients with CE and hemoblastoses
      treated at the Hematology Research Center, Ministry of Health of the Russian
      Federation, in 2006 to 2012. The diagnosis of CE was established according to the
      single isolation of Candida spp. from blood cultures and the presence of
      infection symptoms. RESULTS: Over 7 years, CE was diagnosed in 57 patients aged
      17 to 77 years (median age 48 years). Among the patients with CE, there was a
      preponderance of those with lymphomas (54%) and acute leukemias (30%). The
      pathogens of CE were C. albicans (33%), C. guilliermondii (26%), C. parapsilosis
      (12%), C. krusei (8%), C. lusitaniae (5%), C. famata (4%), C. tropicalis (4%), C.
      glabrata (4%), and C. pelliculosa (4%). The major risk factors were
      polychemotherapy (85%), granulocytopenia (63%), mucosal Candida spp. colonization
      (82%), the presence of central venous catheter (CVC) (97%), antibiotics (100%),
      and glucocorticosteroids (70%). The infection occurred with the intake of an
      antifungal agent in 33% of the patients; 60% had concomitant infections of other
      etiology. Antifungal agents were given to 52 (91%) patients. Within 30 days after
      CE diagnosis, 20 (35%) patients died; of them 12 (60%) patients showed tumor
      progression concurrent with the infection. The cure rate for CE was significantly
      higher in the use of echinocandin as a first-line drug (92%), in complete or
      partial remission in hemoblastosis (90%), CVC removal (76%) and in the
      administration of an antifungal drug on day 1 of detection of positive blood
      cultures (75%). The cure rate was significantly lower when septic shock developed
      and a patient was transferred to an intensive care unit (15%), when amphotericin
      B was used as a first-line drug (45%), when granulocytopenia occurred (53%), or
      glucocorticoids were given (55%). CONCLUSION: Candida non-albicans constitute a
      high proportion among the pathogens of CE. A number of risk factors influencing
      survival rates in CE have been identified. It is crucial to use echinocandin as a
      first-line agent as soon as possible after isolation of Candida spp. from blood
      cultures.

PMID- 24432600
TI  - [The value of changes in CD8+CD28+ and CD4+CD28+ cells in patients with HIV
      infection concurrent with tuberculosis during treatment].
AB  - AIM: To study the proportion of CD8+CD28+ and CD4+CD28+ cells among the CD8+ and
      CD4+ lymphocytes and the changes in these indicators in patients with HIV
      infection/tuberculosis (HIV/TB) versus those with HIV infection and those with
      TB. SUBJECTS AND METHODS: One hundred and six persons were examined and included
      into 4 study groups: 1) 39 patients with concomitant HIV/TB; 2) 25 patients with
      HIV monoinfection without TB who had not previously received antiretroviral
      therapy; 3) 17 patients with TB without HIV infection; 4) 25 healthy individuals
      (a control group). RESULTS: CD28 expression was found to be much more reduced on
      the CD8 lymphocytes than that on the CD4 ones. This is likely to be due to
      earlier CD8 lymphocyte dysfunction in both the patients with HIV infection and
      those with HIV/TB although the CD4 cell is the basic virus target. CONCLUSION:
      The study of the proportion of CD8+CD28+ cells among the CD8 lymphocytes is of
      more informative value than the determination of that of CD4+CD28+ among the CD4
      lymphocytes.

PMID- 24432601
TI  - [Use of infusion solution remaxol in the combination treatment of patients with
      leptospirosis].
AB  - AIM: To evaluate the efficiency of using remaxol in the combination treatment of
      patients with leptospirosis. SUBJECTS AND METHODS: Thirty patients (29 men and 1
      woman) with leptospirosis were treated with remaxol. The icteric and anicteric
      forms of the disease were diagnosed in 28 and 2 patients, respectively. Moderate,
      severe, and very severe leptospirosis were observed in 3, 24, and 3 cases,
      respectively. Remaxol was injected intravenously as a ready-to-use infusion
      solution 400 ml/day; the treatment duration was 3 to 9 days at the height of the
      disease. RESULTS: Clinical improvement and normalization of laboratory parameters
      were achieved in the course of the disease. There were no deaths. During early
      convalescence at 4-5 weeks of the disease, the patients taking remaxol at the
      height of the disease were substantially more rarely recorded to have general
      weakness, fever, anorexia, myalgia, leukocytosis, increased erythrocyte
      sedimentation rate, and hyperbilirubinemia than those untreated with this drug.
      CONCLUSION: The performed study established the clinical efficacy of remaxol when
      used in the combination treatment of patients with leptospirosis.

PMID- 24432602
TI  - [Human babesiasis].
AB  - The paper describes a case of imported babesiasis caused by Babesia microti. This
      is an account of the second case of babesiasis in the Russian-language medical
      literature. Its clinical picture and laboratory data in the course of the disease
      are depicted and analyzed. Its clinical differential diagnosis with malaria and
      an update on the diagnosis and treatment of babesiasis are discussed.

PMID- 24432603
TI  - [Pneumocystis pneumonia and generalized tuberculosis in HIV-infected patients].
AB  - The paper describes a clinical case of pneumocystis pneumonia in the presence of
      generalized tuberculosis in a female patient with HIV infection. The lack of
      prevention of pneumocystosis and its late diagnosis and treatment resulted in a
      fatal outcome. The problem of early clinical diagnosis in the concurrent course
      of secondary involvements is discussed.

PMID- 24432604
TI  - [The course of parvovirus B19 infection during pregnancy after kidney
      transplantation].
AB  - Having a tropism for erythroid progenitor cells, parvovirus B19 may cause partial
      red cell aplasia and thrombocytopenia. Early diagnosis of parvovirus B19
      infection in immunocompromised patients is needed for timely antiviral therapy. A
      high-risk group for parvovirus B19 infection includes patients with blood
      diseases who receive multiple transfusions of blood components; those who have
      undergone donor organ transplantation and are long taking immunosuppressive
      drugs; and pregnant women. These patients require careful virological monitoring
      for major blood-borne viral infections. This paper describes a clinical case of
      parvovirus B19 infection in a pregnant woman who has undergone kidney
      transplantation and is continuously taking immunosuppressive medications.
      Identification of the cause of severe anemia and timely adequate therapy could
      lead to the recovery of effective erythropoiesis in the patient.

PMID- 24432605
TI  - [Clinical epidemiology: theory and practice].
AB  - The paper gives the definition, goal, and objectives of clinical epidemiology.
      The latter is shown to be an epidemiology section that makes it possible to
      elaborate evidence-based standards for diagnosis, treatment, and prevention and
      to select a respective algorithm of actions for each specific clinical case.
      Randomized controlled trials are the gold standard for obtaining evidence. Scales
      are proposed to evaluate the efficacy of preventive and therapeutic agents: the
      levels of evidence for their efficacy and the level of strength of its evidence.
      The authors propose to set up clinical epidemiology centers, one of whose goals
      should be to introduce a unified system to evaluate the efficacy of preventive
      and therapeutic agents, by using the principles of evidence-based medicine and
      the methods of clinical epidemiology.

PMID- 24432606
TI  - [Vascular stiffness and diastolic heart failure].
AB  - Vascular stiffness is regarded as a result of degenerative processes potentiated
      by aging, hypertension, and other risk factors. Central hemodynamic changes are
      one of the serious sequels of high arterial stiffness, which gives rise to a
      chain of events as a higher postload on the left ventricle, its concentric
      hypertrophy, diastolic dysfunction and increases the overall risk of
      cardiovascular events. The purpose of the review is to discuss the mechanisms of
      vascular stiffness, focusing on the role of this condition in the development of
      chronic heart failure with retained ejection fraction and its pathogenetic
      treatment as a future target.

PMID- 24432607
TI  - [Sepsis: a new look at the problem].
AB  - The recent proceedings of congresses and forums on sepsis were used to write this
      review. The available definitions of sepsis and ideas on its etiology and
      pathogenesis are critically analyzed. There is information on new concepts of
      sepsis and data on a search for new targets, diagnostic and therapeutic
      approaches, and biomarkers. It is hypothesized that there is a mechanism of
      action of bacteria on mitochondrial dysfunction and human hormonal regulation
      with low-molecular weight exometabolites, namely aromatic microbial metabolites.

PMID- 24432608
TI  - [Triple therapy for chronic hepatitis C: practical aspects].
AB  - The paper considers the practical aspects of antiviral therapy with protease
      inhibitors, a new group of antiviral agents, by using the clinical cases of
      treatment in patients with chronic hepatitis C as an example. It gives the
      general points of triple therapy, including indications for its use in previously
      untreated and unresponsive patients, and discusses in detail possible adverse
      events and ways of their prevention and correction.

PMID- 24432609
TI  - [Immunotherapy for infectious diseases: challenges and prospects].
AB  - The fact that many infectious diseases are not effectively controlled with
      etiotropic drugs determines the relevance of a search for alternative methods,
      particularly those based on the modulation of immunity. The review analyzes
      rational approaches to the immunotherapy of infectious diseases, such as
      regulation of acquired immunity; correction of the quantitative and qualitative
      composition of the intestinal microbiota; and modulation of innate immunity.
      Among the drugs affecting the innate components of an immune response, the
      derivatives of muramyl dipeptide (MDP), a structural subunit of bacterial cell
      wall peptidoglycan, stand out in the context of a detailed study of the cellular
      and molecular mechanisms of action. The fact that it is expedient to clinically
      apply these immunomodulators in many diseases accompanied by inadequate infection
      control is beyond question. It is demonstrated that muramyl peptides (MP) may be
      also used to prevent excessive inflammatory responses. The adjuvant properties of
      MDP and its analogues can be employed for therapeutic vaccination. The data that
      the signals transmitted through NOD-like receptors (MP sensors) regulate
      intestinal homeostasis suggest that there is some potential for the use of MDP
      derivatives for the correction of dysbiosis and related immune disorders.
      Whatever the purpose of immunomodulation, the key to its effectiveness is to
      personalize the choice and regimens of immunotropic drugs.

PMID- 24432610
TI  - [Use of darunavir in HIV-infected women during pregnancy].
AB  - The use of antiretroviral drugs (ARVDs) in a mother and a child can reduce the
      risk of vertical transmission of human immunodeficiency virus (HIV) to less than
      1%; therefore, highly active antiretroviral therapy is used in all pregnant women
      regardless of indications for HIV-infection treatment. The major requirements for
      choosing an ARVD to prevent mother-to-child HIV transmission are its high safety
      for a pregnant woman, a fetus, and a baby and its high therapeutic efficacy.
      Clinical trials of darunavir (DRV) in adults and children have shown a high
      virologic response, good tolerance, and safety. Trials and observations have
      demonstrated the high efficacy and safety of a DRV when used in pregnant women.
      Pharmacokinetic studies in pregnant women have indicated the effective and well
      tolerated concentration of a DRV when it is co-administered with low-dose
      ritonavir, which permits the use of a DRV for both the prevention of mother-to
      child HIV transmission and the treatment of pregnant women who require
      antiretroviral therapy. The Russian clinical protocol "Use of ARVDs in the
      package of measures for the prevention of mother-to-child HIV transmission"
      approved by the National Scientific Society of Infectiologists in 2013 recommends
      DRV as an alternative drug in antiretroviral therapy regimens for pregnant women
      to prevent mother-to-child HIV transmission and to treat maternal HIV infection.

PMID- 24432611
TI  - [Dengue fever in Russian tourists who have come from Thailand].
AB  - The review analyzes the major epidemiological and clinical aspects of Dengue
      fever, by providing the clinical examples of using its imported cases. It gives
      algorithms for examining patients who have come from tropical countries with the
      fever of unknown origin. Based on the extensive data available in the literature
      and international guidelines, the authors present treatment algorithms for out-
      and inpatients with Dengue fever. Promising studies of vaccination against Dengue
      fever are analyzed.

PMID- 24432612
TI  - [Use of maraviroc, the first CCR5 receptor antagonist, in HIV treatment
      regimens].
AB  - The paper gives the results of international trials of and guidelines for the use
      of maraviroc, the first CCR5 receptor antagonist, in treatment regimens for HIV
      infected patients. The trials have convincingly shown that the maraviroc
      containing antiretroviral therapy (ART) regimens are highly effective and safe
      for R5-tropic HIV-infected patients regardless of previous ART, baseline HIV RNA
      levels, and CD4+ lymphocyte count. Maraviroc can be recommended for HIV-infected
      patients who have previously received ART and who have been found to have a R5
      tropic virus. The changes in the ART regimen and inclusion of maraviroc may be
      associated with both an ineffective previous treatment regimen and therapy
      induced adverse events. In 2012, Russia's first reagent kit for the determination
      of HIV tropism was put to tests and registered at the Russian Inspectorate for
      the Protection of Consumer Rights and Human Welfare.

PMID- 24432613
TI  - [The clinical and epidemic characteristics of shingles (herpes zoster) and its
      prevention with vaccines].
AB  - The review gives data on the clinical manifestations, complications, and
      epidemiological characteristics of herpes zoster. It discusses prospects for and
      foreign experience with vaccination against chickenpox and exacerbations of
      herpes zoster.

PMID- 24432614
TI  - [Molecular genetic mechanisms of teratozoospermia].
AB  - Teratozoospermia is one of the important factors contributing to male
      infertility, and its pathogenesis is not yet clear. Recent years have witnessed
      some progress in the researches on sperm morphology, and some genes have been
      confirmed to be correlated with spermatogenesis. Aiming to provide some evidence
      for the pathogenesis of teratozoospermia, this paper reviews the relevant
      literature in the past five years addressing such special teratozoospermia as
      globozoospermia, nuclear vacuoles, decapitated spermatozoa, excessive residual
      cytoplasm, dysplasia of the fibrous sheath, and primary ciliary dyskinesia, and
      elaborates on the molecular genetic mechanisms of DPY19L2, AR, PRM1, GBA2, PCI,
      CREM, TH2A, TH2B, ODF1, Cntrob, OAZ-t, HOOK1, SPEM1, GAT1, PRSS21, 15-LOX, Sptrx,
      AKAP3, AKAP4, DNAI1, DNAH5, RSPH4A, TXNDC3, CCDC39, LRRC6, LRRC50, KTU and so on.
      Meanwhile, this review also presents an overview on the latest advances in
      assisted reproductive technology and its outcomes in the treatment of
      teratozoospermia patients in order to provide a theoretical basis for the
      diagnosis and treatment of male infertility.

PMID- 24432615
TI  - [Mammalian target of rapamycin regulates androgen receptor and Akt
      phosphorylation in prostate cancer 22RV1 cells].
AB  - OBJECTIVE: To investigate the roles of the mammalian target of rapamycin-1 and -2
      (mTORC1 and TORC2) in the proliferation and apoptosis of prostate cancer 22RV1
      cells. METHODS: After silencing mTORC1 and TORC2, we examined the proliferation
      and apoptosis of prostate cancer 22RV1 cells by methylthiazol tetrazolium (MTT)
      assay and flow cytometry, respectively, and detected the expressions of the
      androgen receptor (AR) and Akt phosphorylation in the prostate cancer 22RV1 cells
      by Western blot after transfecting Raptor-siRNA and Rictor-siRNA to the 22RV1
      cells. RESULTS: MTT showed that the prostate cancer 22RV1 cells had no
      significant change in the growth rate after mTORC1 silence (P > 0.05), but their
      proliferation was markedly inhibited after mTORC2 silence (P < 0.01). Flow
      cytometry revealed a dramatic increase in the apoptosis of the 22RV1 cells after
      mTORC1 silence (P < 0.01), but no obvious change after mTORC2 silence (P > 0.05).
      Western blot exhibited that mTORC1 silence significantly increased the expression
      of AR and Akt phosphorylation (P < 0.05), while mTORC2 silence markedly decreased
      them (P < 0.05). CONCLUSION: mTORC2 is not only required for the survival of
      prostate cancer 22RV1 cells, but also a promising therapeutic target of prostate
      cancer.

PMID- 24432616
TI  - [Expressions of netrin-1 and UNC5B in prostate cancer and their clinical
      significance].
AB  - OBJECTIVE: To search for a new diagnostic biomarker for prostate cancer by
      comparing the differences in the expressions of netrin-1 and UNC5B in prostate
      cancer cells with different invasive abilities. METHODS: We examined the
      expressions of netrin-1 and UNC5B in five prostate cancer cell lines DU145,
      22RV1, PC3, PC3M and RWPE-1 using RT-PCR and Western blot, and positioned the
      ligands netrin-1 and its receptor UNC5B in the prostate cancer cells by
      immunofluorescence. RESULTS: Both netrin-1 and UNC5B were expressed in the
      prostate cancer cells, and the expression of netrin-1 was significantly increased
      in highly invasive cells (P < 0.05), while that of UNC5B in RWPE-1 (normal) cells
      (P < 0.05). CONCLUSION: The expressions of netrin-1 and UNC5B are closely related
      to the infiltration and progression of prostate cancer, and expected to be as
      potential biomarkers for predicting the malignancy degree of prostate cancer.

PMID- 24432617
TI  - [Establishment and evaluation of an automatic method for seminal plasma gamma-L
      glutamyl transpeptidase detection].
AB  - OBJECTIVE: To establish an automatic method for seminal plasma gamma-L-glutamyl
      transpeptidase (GGT) detection and evaluate its accuracy, repeatability and
      linear range. METHODS: We detected the GGT activity in the seminal plasma by rate
      assay, and established the detection parameters on an automatic biochemical
      analyzer. Then, we evaluated the reagent blank absorbance, accuracy,
      repeatability and linear range of the automatic method, and compared the results
      obtained from the method and the seminal plasma GGT detection kit (Xindi
      Biological Pharmaceutical Engineering Co., Ltd, Nanjing, China) commonly used in
      clinical laboratories. RESULTS: The average absorbance of reagent blank was
      0.0476, and the average change rate of blank absorbance (deltaA/min) was
      0.000168. The coefficients of variation (CV) for 3 seminal plasma samples with
      high, middle and low GGT activity detected for 10 times, respectively, were
      0.26%, 4.83% and 1.60%. The accuracy of the automatic method was evaluated by a
      comparison test, and the relative deviation for each concentration point of 40
      seminal plasma samples ranged from 13.38% to 11.05%, which met the requirement of
      < 15%. There was a good linear relationship (r > 0.99) when the seminal plasma
      GGT activity was between 299 and 1 833 U/L. A significant positive correlation
      was found between the seminal plasma GGT detection kit (a colorimetric method) as
      the control and the automatic method as the test reagent in the results of 115
      seminal plasma samples (r = 0.981, P < 0.01), with a Kappa value of 0.776 (P <
      0.05) and a coincidence rate of 90.43%. CONCLUSION: The established automatic
      method to detect seminal plasma GGT activity has a low reagent blank, good
      repeatability and accuracy, and fine concordance with the colorimetric method
      commonly used in clinical laboratories. It is simple, rapid and suitable for
      screening large numbers of samples, avoids the necessity of diluting the seminal
      plasma sample, and saves a lot of manpower and reagents.

PMID- 24432618
TI  - [Impact of sperm DNA fragmentation index and sperm malformation rate on the
      clinical outcome of ICSI].
AB  - OBJECTIVE: To evaluate the sperm DNA fragmentation index (DFI) and sperm
      malformation rate (SMR) before intracytoplasmic sperm injection (ICSI) and their
      impact on the clinical outcome of ICSI. METHODS: This study included 79 cycles of
      ICSI because of oligoasthenozoospermia. We detected the sperm concentration,
      percentage of progressively motile sperm, DFI and SMR at 3 to 6 months before
      ICSI, and analyzed the relationship of DFI and SMR with the outcome parameters.
      RESULTS: Of the 79 oligoasthenozoospermia cases, DFI was found to be normal (< or
      = 25%) in 51 and abnormal (> 25%) in the other 28, significantly increased in the
      latter (14.18% vs 41.47%), and coincidently, SMR, too, was normal (< or = 96%) in
      51 cases and abnormal (> 96%) in 28, significantly higher in the abnormal than in
      the normal cases (87.88% vs 98.46%). There were no significant differences
      between the normal and abnormal DFI groups in age, females'BMI, number of oocytes
      retrieved, and number of embryos transferred, nor between the normal and abnormal
      SMR groups in the number of fertilized oocytes and quality embryos, biochemical
      pregnancy, clinical pregnancy, and early pregnancy loss. Sperm DFI was
      significantly positively correlated with SMR (r = 0.231, P < 0.05). CONCLUSION:
      ICSI may reduce the rates of biochemical pregnancy and clinical pregnancy for men
      with increased sperm DFI (> 25%) and SMR (> 96%) by strict detection criteria,
      but with no statistically significant difference from normal males. Our findings
      need to be supported by further studies with larger sample sizes.

PMID- 24432619
TI  - [Impact of perceived male infertility factors on penile erectile function].
AB  - OBJECTIVE: To evaluate the impact of the factors of perceived male infertility on
      men's penile erectile function. METHODS: Using the 5-item version of the
      International Index of Erectile Function (IIEF-5), we investigated the penile
      erectile function among 245 infertile men (infertility group) and another 52
      males having physical checkup for planned conception (checkup group), the former
      further divided into four subgroups according to the factors of infertility: male
      factor, female factor, bilateral factor, and unknown factor. We compared the
      total and item scores of IIEF-5 among different groups. RESULTS: Mild or mild
      moderate ED was found in 50.61% of the infertile men, with a total IIEF-5 score
      of 21.24 +/- 2.58. The total and item scores of IIEF-5 were markedly higher in
      the male factor than in the female factor subgroup (P < 0.01), but with no
      significant difference between the male factor subgroup and the bilateral and
      unknown factor subgroups (P > 0.05), except the score on confidence. The scores
      were significantly lower in the bilateral and unknown factor subgroups than in
      the female factor subgroup (P < 0.05), with no remarkable difference between the
      former two. In the infertility group, the total and item scores of IIEF-5 were
      markedly higher in those with education above high school than in those with high
      school or lower education (P < 0.01), but not correlated with age and infertility
      duration. After adjustment for education background, the total IIEF-5 score and
      the scores on confidence and satisfaction were significantly lower in the
      infertility than in the checkup group (P < 0.05), and 15.38% of the men in the
      latter group had mild ED, dramatically lower than in the former (P < 0.01).
      CONCLUSION: Perceived infertility may cause ED in males, and a higher incidence
      rate is associated with lower education background of the men.

PMID- 24432620
TI  - [Modified prepuce-degloving repair for urethrocutaneous fistula following
      hypospadias surgery].
AB  - OBJECTIVE: To investigate the clinical effect and application value of the
      modified method of prepuce-degloving repair (PDR) in the treatment of
      urethrocutaneous fistula (UCF) following hypospadias surgery. METHODS: We
      retrospectively analyzed 87 cases of UCF caused by hypospadias repair from May
      2001 to December 2011, of which 61 were treated by simple closure or Y-V plasty
      of the fistula (group A), and the other 26 by modified PDR (group B). We compared
      the success rate of surgery and long-term recurrence between the two groups.
      RESULTS: The total success rates of repair were 78.7 and 96.2% in groups A and B,
      respectively. Thirteen cases in group A did not respond to surgery, of which 6
      failed to be cured by the second operation but later were treated successfully by
      modified PDR. In comparison, there was only 1 case of failure in group B, which
      was cured by a second PDR. CONCLUSION: Modified PDR can significantly improve the
      success rate and reduce the recurrence rate of UCF after hypospadias surgery,
      which deserves wide clinical application.

PMID- 24432621
TI  - [Staged hypospadias surgery for adult males].
AB  - OBJECTIVE: To explore the necessity of staged hypospadias surgery for adult men
      in order to improve the success rate of operation. METHODS: We retrospectively
      analyzed 52 cases of hypospadias treated in our department from January 2004 to
      January 2012. The patients were adult males at the mean age of 22 years and all
      had a history of urethroplasty, with curvature of the penis and scar tissues on
      the penile skin. We removed the scarred fibrous tissues on the ventral cavernosa
      and cut off the urethral plate following foreskin-degloving. For those still with
      penile curvature, we straightened the penis by plication of the dorsal tunica
      albuginea, with the length of the anterior urethral defect > 50% of that of the
      penis after penis-straightening. The patients were assigned to group 1 (n = 20)
      to receive stage-I foreskin vascular pedicle flap urethroplasty and group 2 (n =
      32) to undergo foreskin-shaping at the ventral aspect of the penis following
      penile straightening to prepare the urethra plate for stage-II Duplay
      urethroplasty after 6-12 months. RESULTS: The success rates of urethroplasty were
      25 and 56.3% in groups 1 and 2, respectively, with the post-urethroplasty
      incidence rates of urinary fistula of 50 and 21.9%, urethral stricture of 15 and
      9.4%, local wound infection of 30 and 25%, and urethral rupture of 20 and 12.5%.
      There were statistically significant differences between the two groups in the
      incidence of urinary fistula and the success rate of urethroplasty, but not in
      urethral stricture, local wound infection and urethral rupture. CONCLUSION: For
      adult hypospadias patients with a history of urethroplasty, especially those with
      obvious penile curvature, long urethral defect and insufficient foreskin, staged
      hypospadias surgery is preferable, which can dramatically increase the success
      rate of second-stage urethroplasty.

PMID- 24432622
TI  - [Cardura monotherapy versus combination therapy of cardura and tolterodine L
      tartrate tablets for II degrees  ? benign prostatic hyperplasia with overactive
      bladder].
AB  - OBJECTIVE: To evaluate the effectiveness of the monotherapy of Cardura and the
      combination therapy of Cardura and Tolterodine L-Tartrate Tablets for II degrees 
      ? benign prostate hyperplasia (BPH) with overactive bladder (OAB). METHODS: This
      study included 87 cases of BPH with OAB, with a disease course > or = 3 months,
      daily urination > or = 8 times, nocturnal urination > or = 2 times, urine volume
      < 200 ml per time, International Prostate Symptom Score (IPSS) > or = 8, OAB
      symptom score (OABS) > or = 3, quality of life score (QOL) > or = 3, post-void
      residual (PVR) < or = 100 ml, maximum urinary flow (Qmax) > or = 5 ml/s, prostate
      weight 25-50 g, and PSA < 4 microg/L. We randomized the patients to a monotherapy
      group (n = 44) and combination group (n = 43), the former treated with Cardura 4
      mg qd, and the latter with Cardura 4 mg + Tolterodine L-Tartrate Tablets 4 mg qd,
      both for 8 weeks. Then we recorded the IPSS, OABS, Qmax, PVR, PSA, and adverse
      events. RESULTS: The baseline parameters showed no significant differences
      between the two groups (P > 0.05). In comparison with the baseline, both the
      monotherapy group and the combination therapy group showed significant decreased
      in the IPSS (16.50 +/- 4.27 vs 13.68 +/- 3.69 and 15.51 +/- 3.80 vs 11.49 +/-
      2.75), urine storage symptom score (10.48 +/- 2.75 vs 7.98 +/- 2.34 and 9.47 +/-
      2.31 vs 5.74 +/- 1.66), OABS (8.55 +/- 2.69 vs 6.32 +/- 1.97 and 8.21 +/- 2.55 vs
      4.44 +/- 1.62), urgent micturition score (4.25 +/- 1.06 vs 3.23 +/- 0.99 and 4.07
      +/- 0.83 vs 2.26 +/- 1.05), QOL (5.36 +/- 0.72 vs 3.43 +/- 0.66 and 5.07 +/- 0.86
      vs 2.37 +/- 0.76) and PVR ([44.55 +/- 22.39] vs [38.30 +/- 20.20] ml and [36.19
      +/- 21.21] vs [24.98 +/- 17.60] ml) (P < 0.01). All the six parameters were
      significantly more improved in the combination therapy group than in the
      monotherapy group (P < 0.01), but there were no remarkable differences between
      the groups in Qmax and voiding symptom score (P > 0.05). Neither group exhibited
      significant changes in the PSA level and prostate weight after treatment as
      compared with the baseline (P > 0.05). No acute urinary retention and other
      severe adverse reactions were observed during the medication. CONCLUSION: Both
      Cardura monotherapy and the combination therapy of Cardura + Tolterodine L
      Tartrate Tablets can improve II ? BPH with OAB, and the latter has an even better
      efficacy than the former.

PMID- 24432623
TI  - [Androgen deprivation therapy for prostate cancer: a follow-up study of the
      patients' survival time].
AB  - OBJECTIVE: To explore the long-term survival and prognosis of prostate cancer
      patients after treated by androgen deprivation therapy. METHODS: We conducted a
      follow-up study of 124 patients with prostate cancer treated by androgen
      deprivation therapy, and compared the survival times of the patients with
      different pathological grades and clinical characteristics using Kaplan-Meiers
      survival curves. RESULTS: The mean survival time of the 124 patients after
      androgen deprivation therapy was 5. 912 years, with the median survival time of
      7.81 years. The patients with bone metastases showed a shorter survival time than
      those with non-bone metastasis (P = 0.04). Pathological grades and PSA levels
      were not prognostic factors. No significant differences were found in the mean
      survival time between those died of prostate cancer (n = 35) and those from other
      factors (n = 23) (P = 0.50). CONCLUSION: Bone metastasis is an important
      prognostic factor in advanced prostate cancer following androgen deprivation
      therapy, which is more significantly correlated with the survival time of the
      patients than tumor grades and clinical classification.

PMID- 24432624
TI  - [Multiple urethral metastases from prostate adenocarcinoma after radical
      prostatectomy: a case report and literature review].
AB  - OBJECTIVE: To investigate the mechanism and management of multiple urethral
      metastases from prostate adenocarcinoma after radical prostatectomy. METHODS: We
      summed up the experience in the management of a case of multiple urethral
      metastases from prostate adenocarcinoma after radical prostatectomy and reviewed
      relevant literature. The patient was a 79-year-old male, who had received radical
      prostatectomy for prostate adenocarcinoma 13 years before, and presented with
      macrohematuria and dysuria in the past 2 weeks. A nodule (1.0 x 0.5 cm) was found
      in the urethral meatus. Cystourethroscopy revealed multiple tumors in the urethra
      and biopsy indicated them to be metastases from prostate adenocarcinoma. The
      preoperative level of PSA was 3.01 microg/L. As treatment, we performed radical
      urethrectomy and cystostomy. RESULTS: Postoperative pathology showed multiple
      metastases of prostate adenocarcinoma to the urethra, involving the urethral
      sphincter and corpus spongiosum. Immunohistochemistry revealed PSA (+), PsAP(+),
      AR(+) and CK 7(-). The surgical margin was negative. The patient recovered well
      postoperatively, with a PSA level of 1.00 microg/L. CONCLUSION: Urethral
      metastasis of prostate adenocarcinoma after radical prostatectomy is rarely seen
      clinically. For the treatment of multiple urethral metastases, surgery is the
      first choice and radical urethrectomy is an appropriate management.

PMID- 24432625
TI  - [Clinical diagnosis and treatment of male Kallmann syndrome].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of male Kallmann syndrome.
      METHODS: We retrospectively analyzed the clinical data of 12 cases of male
      Kallmann syndrome, 3 treated for male sterility and the other 9 for secondary sex
      characteristics dysplasia and external genitalia developmental anomalies, all by
      combined replacement therapy with human chorionic gonadotropin (hCG), human
      menopause gonadotropin (hMG) and testosterone undecanoate for 6 months to 3
      years. We compared the secondary sexual development and serum sex hormone levels
      of the patients before and after treatment. RESULTS: After 9 months of treatment,
      all the 12 patients showed significant improvement in the penile length,
      testicular volume and sex hormone levels (P < 0.01), with different degrees of
      promotion of the secondary sexual development. Three married cases could have
      normal sexual intercourse, and one of them achieved normal pregnancy. CONCLUSION:
      The clinical characteristics of Kallmann syndrome include lack of gonadotropins,
      lower gonad function and loss or reduction of olfactory sensation. Replacement
      therapy with hCG, hMG and androgens is an effective treatment method. However, no
      effective therapy is now available for olfactory dysfunction. Early diagnosis and
      hormone replacement therapy can best alleviate its clinical symptoms and
      eventually achieve fertility.

PMID- 24432626
TI  - [Qilin pills combined with levofloxacin for asthenospermia accompanied with
      accessory sex gland infection: a clinical observation].
AB  - OBJECTIVE: To observe the efficacy of the combination of Qilin Pills and
      levofloxacin in the treatment of asthenospermia accompanied with accessory sex
      gland infection. METHODS: We randomly assigned 80 asthenospermia patients with
      accessory sex gland infection to groups 1 and 2 of equal number, the former
      treated with Qilin Pills + levofloxacin, and the latter with levofloxacin only.
      Qilin Pills were administered at the dose of 6 g tid for 30 days, and
      levofloxacin at the dose of 0.5 g qd for 20 days. We obtained semen parameters,
      including the percentage of progressively motile sperm and peroxidase-positive
      white blood cell (WBC) count, before and after medication, and compared the
      clinical effects between the two groups. RESULTS: All the patients accomplished
      the clinical trial. The therapeutic effectiveness rates in improving progressive
      sperm motility were 60% in group 1 and 17.5% in group 2, with statistically
      significant differences between the two groups (P < 0.05). As for the peroxidase
      positive WBC count in semen, the effectiveness rates were 87.5% and 82.5%,
      respectively, with no significant differences between the two groups (P > 0.05).
      CONCLUSION: For the treatment of asthenospermia accompanied with accessory sex
      gland infection, Qilin Pills combined with levofloxacin is evidently better than
      levofloxacin alone in improving sperm motility, and it has no obvious adverse
      effects.

PMID- 24432627
TI  - [Yiqi Zhujing granule for idiopathic oligoasthenozoospermia: a clinical study].
AB  - OBJECTIVE: To assess the efficacy of Yiqi Zhujing Particle in the treatment of
      idiopathic oligoasthenozoospermia. METHODS: We equally randomized 78 patients
      with idiopathic oligoasthenozoospermia to a control group and a Yiqi Zhujing
      group, the former treated with oral medication of zinc gluconate liquid (10 ml,
      bid) and vitamin E (100 mg, bid), and the latter given Yiqi Zhujing Granule (1
      packet, bid) in addition, both for 3 months. We compared the semen parameters and
      biochemical indexes of the seminal plasma obtained before and after medication
      between the two groups of patients. RESULTS: After 3 months of treatment,
      remarkable improvement was observed in the percentage of progressively motile
      sperm and sperm viability in the control group (P < 0.05) as well as in the total
      sperm count, sperm concentration, percentage of progressively motile sperm, and
      sperm viability in the Yiqi Zhujing group (P < 0.05). The total sperm count,
      sperm concentration, percentage of progressively motile sperm, and sperm
      viability were even more significantly improved in the Yiqi Zhujing than in the
      control group (P < 0.05). Besides, both groups showed different degrees of
      improvement in the biochemical indexes of the seminal plasma, and the Yiqi
      Zhujing group exhibited even more significant improvement in seminal plasma zinc,
      alpha-glucoside enzyme, seminal plasma fructose, and acid phosphatase than the
      control (P < 0.05). The improvement of sperm concentration was correlated
      positively with the change of seminal plasma zinc (r = 0.201, P < 0.05) but
      negatively with that of seminal plasma fructose after treatment (r = -0.136, P <
      0.05). There was a positive correlation between the alpha-glucoside enzyme level
      and sperm viability (r = 0.314, P < 0.05). CONCLUSION: Yiqi Zhujing Particle is
      effective for idiopathic oligoasthenozoospermia by significantly improving the
      total sperm count, sperm concentration, percentage of progressively motile sperm,
      sperm viability, seminal plasma zinc, seminal plasma fructose, and alpha
      glucoside enzyme.

PMID- 24432628
TI  - [Animal models of chronic prostatitis: an update].
AB  - Chronic prostatitis is a disease caused by a number of factors characterized by
      perineal discomfort, pelvic pain, irritative urination symptoms and even sexual
      dysfunction, and histologically with infiltration of poly-and mononuclear cells
      in the interstitial connective tissue. Research on this disease has somewhat been
      hindered, for its pathogenesis and diagnostic criteria are not yet clear. Animal
      models can help to explain the pathogenesis of chronic prostatitis and chronic
      pelvic pain syndrome. This article presents an overview on the advantages and
      limitations of rodent models in the studies of this disease.

PMID- 24432629
TI  - [Progress in researches on male immunocontraception].
AB  - The ideal goal of male immunocontraception is to develop a safe, effective,
      convenient, acceptable and reversible contraceptive vaccine. Current studies
      mainly focus on screening the most suitable target antigens from reproductive
      hormones and sperm functional proteins for the development of immuno
      contraceptive vaccines. The vaccine targeting reproductive hormones has not been
      widely used due to its different degrees of side effects and complicated
      operation. Recent studies show the practicability and applicability of the immuno
      contraceptive vaccine targeting sperm specific antigens, but its development is
      confronted with many challenges, such as how to select appropriate target
      antigens, how to enhance the immunogenicity of the vaccine, how to choose
      appropriate drug-delivery ways, how to reduce its side effects, and how to
      decrease its cost.

PMID- 24432630
TI  - [Markers of prostate cancer stem cells: research advances].
AB  - Prostate cancer is one of the most seriously malignant diseases threatening men's
      health, and the mechanisms of its initiation and progression are not yet
      completely understood. Recent years have witnessed distinct advances in
      researches on prostate cancer stem cells in many aspects using different sources
      of materials, such as human prostate cancer tissues, human prostate cancer cell
      lines, and mouse models of prostate cancer. Prostate cancer stem cell study
      offers a new insight into the mechanisms of the initiation and progression of
      prostate cancer and contributes positively to its treatment. This article
      presents an overview on the prostate cancer stem cell markers utilized in the
      isolation and identification of prostate cancer stem cells.

PMID- 24432631
TI  - [Cardiovascular-protective effect of tadalafil in the treatment of erectile
      dysfunction].
AB  - The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth
      muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine
      monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO)
      donor. Tadalafil is the first PDE 5 inhibitor approved by FDA for the treatment
      of ED. Recent studies have shown several pleiotropic beneficial effects of PDE-5
      inhibitors in patients with cardiovascular diseases (coronary heart disease,
      hypertension, heart failure, and pulmonary arterial hypertension) and diabetes
      mellitus. It has been demonstrated that tadalafil can not only improve sexual
      function, but also elevate the endothelial cell-derived NO level, activate
      protein kinase A, upregulate the intracellular Ca2+ concentration, and improve
      hemodynamic indexes. Thus, the PDE-5 inhibitor tadalafil, with its cardiovascular
      protective effect, can be a therapeutic option for the treatment of ED patients
      with cardiovascular disease.

PMID- 24432632
TI  - [Application of chemometric methods in chromatographic analysis of complex
      systems].

PMID- 24432633
TI  - [Influence of overalkylation in enzymatic digestion on the qualitative and
      quantitative analysis of proteins].
AB  - Reduction and alkylation with iodoacetamide (IAA) of the disulfide bridges in
      proteins are important procedures used in protein digestion. But the alkylation
      with IAA takes place not only on cysteine residues but also on other amino acid
      residues. Here we conducted a systematic study of all alkylated peptides under
      the usual protein digestion conditions. It showed that the potentials for
      alkylation reaction of different amino acid residues were cysteine > N-terminal
      amino acid > aspartic acid > glutamic acid > histidine > asparagine > lysine >
      tyrosine. Furthermore, we found that the alkylation reaction happened either
      exclusively or cooperatively among different amino acid residues in the same
      peptide. Based on the qualitative results on overalkylation at several peptides,
      the targeted multiple reaction monitoring (MRM) technique was used to evaluate
      the effect of overalkylation on quantitative protein analysis. The results showed
      that overalkylation has large effect on the qualitative and quantitative analysis
      of proteins and should be avoided in enzymatic digestion.

PMID- 24432634
TI  - [Rapid determination of total residues of ribavirin and its metabolites in
      chicken and chicken products by ultra-performance hydrophilic interaction
      chromatography-tandem mass spectrometry].
AB  - An analytical method was developed for the determination of total residues of
      ribavirin and its phosphorylated metabolites in chicken and its products by
      hydrophilic interaction chromatography-tandem mass spectrometry. The samples were
      extracted with acetonitrile containing 1% (v/v) acetic acid under ultrasonic
      condition and then enzymatically hydrolysed with acid phosphatase at 37 degrees
      C. After liposoluble substances being removed with hexane, C18 and PSA dispersion
      solid phase extraction (DSPE) was introduced to cleanup procedures. The
      separation was performed on an ultra-performance hydrophilic interaction
      chromatographic (HILIC) amide column under a gradient elution using acetonitrile
      and 0.1% formic acid. The analytes were detected in the positive electrospray
      ionization and multi-reaction monitoring (MRM) mode. In the range of 1-200
      microg/kg, the correlation coefficient was greater than 0.999. The limit of
      detection (LOD, S/N > or = 3) was 1 microg/kg and the limit of quantification
      (LOQ, S/N > or = 10) was 5 microg/kg. The recoveries of ribavirin spiked at three
      levels ranged from 67.8% to 112.7% with the relative standard deviations (RSDs)
      of 6.1%-13.6%. The results of the determination of ribavirin in various real
      samples showed that the method is simple, rapid, accurate and suitable for the
      determination of total residues of ribavirin and its metabolites in chicken and
      its products.

PMID- 24432635
TI  - [Determination of three azaspiracids in edible shellfishes by QuEChERS method
      combined with ultra high performance liquid chromatography-tandem mass
      spectrometry].
AB  - An ultra high performance liquid chromatography-tandem mass spectrometric method
      (UHPLC-MS/MS) was developed for the simultaneous determination of three natural
      forms of azaspiracids (AZA-1, AZA-2 and AZA-3) in edible shellfishes such as
      mussels, oysters, clams and scallops. The samples were homogeneously extracted
      with acetonitrile-water (85: 15, v/v). The resultant supernatants were purified
      with QuEChERS method and filtrated by 0.2 microm microporous filters. The
      separation was performed on an Agilent ZORBAX Eclipse Plus C18 column (100 mm x
      2.1 mm, 1.8 microm) with the gradient elution using acetonitrile/water
      (containing 5 mmol/L ammonium acetate and 0.1% formic acid) as mobile phases. The
      three azaspiracids were detected using positive electrospray ionization (ESI +)
      followed with multiple reaction monitoring (MRM), and quantified by external
      standard calibration method. The calibration curves showed good linearity in the
      range of 1-100 microg/kg with the correlation coefficients (r2) greater than
      0.995. The limits of quantification (LOQ, S/N = 10) were 1.0 microg/kg for all
      the three AZAs. The average recoveries of azaspiracids spiked in the matrix at
      the levels of 10, 20 and 50 microg/kg ranged from 71% to 108%. The relative
      standard deviations (RSDs) of inter-day and intra-day determinations were less
      than 10% (n = 6). The samples from several areas within and outside of China were
      screened, and some of the samples showed positive for azaspiracids. The developed
      method is easy to operate, very reproducible, sensitive, and efficient. It can be
      applied to the determination of the three forms of AZAs in the edible shellfishes
      as well shellfish products.

PMID- 24432636
TI  - [Simultaneous determination of penicillin and their major enzymatic metabolites
      in milk and milk powder by high performance liquid chromatography-tandem mass
      spectrometry].
AB  - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS)
      method has been developed for the determination of eight compounds in milk and
      milk powder. They are four penicillins (penicillin G, penicillin V, amoxicillin
      and ampicillin) and four major beta-lactamase enzymatic metabolites of them
      (penilloic acid G, penilloic acid V, amoxiilloic acid and ampilloic acid). The
      compounds were extracted from the samples with acetonitrile and water, cleaned-up
      by HLB solid-phase extraction cartridges, and then detected by HPLC-MS/MS and
      quantified by external standard method. The linearities were satisfactory with
      the correlation coefficients > 0.99 at the mass concentrations ranging from 4
      microg/L to 200 microg/L for penicillins and from 10 microg/L to 500 microg/L for
      enzymatic metabolites. The limits of detection and the limits of quantification
      were 5-50 microg/kg (S/N > or = 3) and 8-100 microg/kg (S/N > or = 10),
      respectively. The average recoveries of the eight compounds were 83.48%-96.97% in
      milk and 82.70%-95.14% in milk powder. The relative standard deviations (RSDs) in
      milk and milk powder were 3.86%-10.87% and 3.02%-9.81%, respectively. In
      conclusion, the established method is convenient, accurate and sensitive so that
      it can be applied to the determination of penicillin residues and enzymatic
      metabolites in milk and milk powder.

PMID- 24432637
TI  - [Determination of six novel amide fungicides in vegetables and fruits by liquid
      chromatography-tandem mass spectrometry].
AB  - A method was developed for the simultaneous determination of mepanipyrim,
      silthiofam, boscalid, fluopicolide, mandipropamid, cyflufenamid in vegetables and
      fruits by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytes
      were extracted from the samples by acetonitrile and purified by Florisil SPE. The
      six novel amide fungicides were separated on a Poroshell 120 EC-C18 column with
      the mobile phases of water and acetonitrile, and finally detected by MS/MS with
      positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM)
      mode, quantified by external standard method. Under the optimal analytical
      conditions, the correlation coefficients (r) of the six novel amide fungicides
      were not lower than 0. 999 0 in the concentration range from 0.5 to 100 microg/L.
      The limits of detection (S/N > or = 3) of the method were 0.15 microg/kg for
      boscalid, silthiofam, mandipropamid, cyflufenamid, 0.10 microg/kg for mepanipyrim
      and 0.17 microg/kg for fluopicolide. The recovery tests were performed for the 7
      types of vegetables and the 3 types of fruits at the spiked levels of 0.5, 5 and
      50 microg/kg, and the recoveries of the six analytes ranged from 65% to 124% with
      the relative standard deviations (RSDs, n = 5) of 1%-18%. The matrix effects in
      vegetables and fruits of the six amide fungicides were significantly reduced by
      the purification of Florisil SPE compared with the modified QuEChERS. The method
      is easy, fast, sensitive and accurate, and can meet the requirements of the
      determination of the six amide fungicide residues in vegetables and fruits.

PMID- 24432638
TI  - [Screening and confirmation of carcinogenic dyes in textiles by high performance
      liquid chromatography-linear ion trap/orbitrap high resolution mass
      spectrometry].
AB  - A method of high performance liquid chromatography-linear ion trap/Orbitrap high
      resolution mass spectrometry (HPLC-LTQ/Orbitrap MS) was used to screen and
      confirm carcinogenic dyes in textiles. The analytes were extracted from textile
      samples with pyridine/water (1/1, v/v) in a water bath under controlled
      conditions (95 degrees C, 150 r/min), and then filtered with a 0.22 microm
      polytetrafluoroetylene (PTFE) membrane. The eluates were separated on a CAPCELL
      PAK C18 column (100 mm x 2.0 mm, 5 microm) using gradient elution with
      acetonitrile/ 5 mmol/L ammonium acetate aqueous solution containing 0.01% formic
      acid (in positive mode) and acetonitrile/5 mmol/L ammonium acetate aqueous
      solution (in negative mode), and finally detected by HPLC-LTQ/Orbitrap MS in ESI
      modes. Full scan experiments were performed over the range of m/z 200-800. The
      screening and quantitative analysis were carried out by the accurate mass of
      quasi-molecular ion and the peak area in extracted chromatogram with accurate
      mass, respectively. The confirmatory analysis for target compounds was performed
      with the retention time and qualitative fragments obtained by data-dependent scan
      mode. Under the optimal conditions, nine carcinogenic dyes were routinely
      detected with mass accuracy below 5 x 10(-6) (5 ppm), and good linearities were
      provided in their respective linear ranges with correlation coefficients higher
      than 0.99. The limits of detection were in the range of 0.125-25 mg/kg. The
      average recoveries at three spiked levels were in the range of 62.13%116.28% with
      the relative standard deviations (RSDs) lower than 15%. The proposed method was
      applied to screen and confirm the nine carcinogenic dyes in textile samples. It
      is convenient and reliable.

PMID- 24432639
TI  - [Rapid determination of N-methyl, propyl-morpholinium cation by ion-pair
      chromatography on monolithic column with indirect ultraviolet detection].
AB  - A fast analytical method was developed for the determination of N-methyl,
      propylmorpholinium cation (MPMo) without UV absorption group by ion-pair
      chromatography-indirect UV detection. Chromatographic separation was performed on
      a reversed-phase silica-based monolithic column using background UV absorption
      reagent aqueous solution-ion-pair reagent aqueous solution-organic solvent as the
      mobile phase. The effects of the background UV absorption reagent, detection
      wavelength, ion-pair reagent, organic solvent, column temperature and flow rate
      on the determination of MPMo were investigated. It was found that the
      morpholinium cation could be determined well with (0.5 mmol/L 4-aminophenol
      hydrochloride-0.1 mmol/L 1-heptanesulfonic sodium) aqueous solution-methanol
      (9:1, v/v) as mobile phase at the UV detection wavelength of 230 nm, the column
      temperature of 30 degrees C and the flow rate of 1.0 mL/min. Under these
      conditions, the retention time of MPMo was 2.966 min. The limit of detection for
      MPMo was 0.07 mg/L (S/N = 3). The relative standard deviations (n = 5) for the
      peak area and retention time were 2. 1% and 0.02%, respectively. The method was
      successfully applied to the determination of morpholinium ionic liquid
      synthesized by a chemistry laboratory. Recovery of MPMo after spiking was 98.8%.
      The results showed that this method is simple and rapid.

PMID- 24432640
TI  - [Separation strategy of affinity chromatography for mixed antibodies].
AB  - A mammary gland bioreactor can efficiently express human recombinant monoclonal
      antibody. However, the target products are similar to the bovine antibody in the
      raw emulsion material in properties and structures. Thus it is difficult to
      achieve effective separation of the target products. In this work, the species
      differences between bovine antibody and recombinant human antibody were analyzed
      and a new separation strategy was raised based on it. We employed two kinds of
      affinity chromatography to separate these two antibodies from each other and
      studied the effect of elution mode upon separation. The results demonstrated that
      Protein A affinity chromatography could get hybrid antibodies using gradient
      elution mode, but hardly separate the recombinant human antibody and bovine
      antibody from each other. In contrast, the combination of Protein A affinity
      chromatography and displacement chromatography could separate the hybrid
      antibodies effectively and finally give recombinant human IgG (rHGG) product with
      the purity of 95% and the yield of more than 95%. Immuno-affinity chromatography
      could also effectively purify recombinant monoclonal antibodies and owned better
      generality, which could be used in purification of recombinant antibody expressed
      by any animal mammary gland. -

PMID- 24432641
TI  - [Matrix effect and retention efficiency of hydrophilic-lipophilic balance
      cartridges in multi-residual determination of veterinary drugs in river water].
AB  - Matrix effect is an important interfering factor in LC-MS quantitative analysis.
      In this paper, matrix effects and retention efficiencies of 33 veterinary drugs
      spiked in river water were studied on hydrophilic-lipophilic balance (HLB)
      cartridges of 3 brands (Waters, Supelco, and CNW), using LC-MS/MS for detection
      and reverse osmosis (RO) water as the control under 500-fold concentration. In RO
      water, only the exogenous matrix effects were observed on three brands of HLB
      cartridges. Most quinolones and tetracyclines showed positive matrix effects.
      Estrogens showed negative matrix effects on two brands of HLB cartridges.
      Sulfonamides were not obviously affected by matrix effects. Chloramphenicols
      showed negative matrix effects on one brand of HLB cartridge. In river water,
      matrix effects were different from those of the RO water due to the combined
      exogenous and endogenous interfering substances. Sulfonamides showed slight
      matrix effects as those in RO water. Most quinolones and tetracyclines showed
      positive matrix effects. Chloramphenicols and estrogens showed negative matrix
      effects. Compared to the external standard method, matrix matched calibration
      method effectively overcame the matrix effects with better quantitative results.
      The recoveries of 33 target veterinary drugs spiked in river water at 50 ng/L and
      200 ng/L levels were in the ranges of 40.3%-146.0% (Waters), 37.8%-104.2%
      (Supelco), and 52.9%-150.1% (CNW) with RSDs (n = 4) of 0.2%-14.6%. The results
      indicated that there was no significant difference in the retention efficiency
      between the 3 HLB cartridges with the matrix matched calibration method. This
      study provided supporting data for the HLB cartridge selection in multi-residual
      determination of the veterinary drugs in river water samples.

PMID- 24432642
TI  - [Simultaneous determination of 23 ester compounds in cigarette water-borne
      adhesives by liquid-liquid extraction and gas chromatography-mass spectrometry].
AB  - A method of gas chromatography-mass spectrometry (GC-MS) with liquid-liquid
      extraction has been developed for the simultaneous determination of 23 ester
      compounds including acetate esters, acrylic esters, metacrylic acid esters and
      phthalate acid esters in cigarette water-borne adhesives. After dispersed in
      water, the sample was extracted by n-hexane solution containing phenyl ethyl
      propionate as internal standard substance. Then, the solution was centrifuged and
      filtrated through a 0.45 microm organic membrane filter. Finally, the solution
      was separated on a DB-WAXETR column (60 m x 0.25 mm x 0.25 microm), and detected
      with MS in selected ion monitoring mode, and quantified by internal standard
      method. The results showed a good linear correlation in the range of 0.4-50.0
      mg/L. The recoveries of the ester compounds spiked in the sample were 81.8%
      109.1%, and the relative standard deviations (RSDs, n = 5) were less than 4%. The
      limits of detection (LODs) and limits of quantification (LOQs were in the ranges
      of 0.02-0.76 mg/kg and 0.04-2.52 mg/kg, respectively. The method is simple, time
      saving, and has high sensitivity and good reproducibility. It can be applied to
      the determination of the 23 ester compounds in cigarette water-borne adhesives.

PMID- 24432643
TI  - [Preparation of a novel hydrophilic open-tubular capillary column by surface
      initiated atom transfer radical polymerization and applications in capillary
      electrochromatography].
AB  - A novel type of glycopolymer brushes grafted open-tubular capillary column (OTCC)
      was developed for the polar compound separation. Briefly, the glycerol
      methacrylate (GMA) polymer brushes were grafted on the inner wall of OTCC by the
      surface initiated atom transfer radical polymerization (SI-ATRP). Next, glucose
      was coupled to the side chains of the GMA polymer brushes to obtain the
      hydrophilic stationary phase (PGMA-N-Glucose). The optimized SI-ATRP reaction
      conditions were GMA/CuCl/CuCl2/cyclohexanol system grafting at 25 degrees C for 1
      h. After the glucose coupling, the column back pressure was about 3,585 kPa. The
      structure of the glycopolymer brushes on the inner surface of OTCC was
      characterized by scanning electron microscopy (SEM). The glycopolymer grafting
      resulted in the formation of three-dimensional wave-like polymer structure on the
      inner surface of OTCC and largely increased the interior surface area. Therefore,
      improved column efficiency and loading capacity can be achieved. Under the
      optimized conditions, the electro osmotic flow (EOF) strength of the glycopolymer
      brushes grafted OTCC was obviously less than that of the bare column when the pH
      value of the mobile phase ranging from 3 to 11. Using the glycopolymer brushes
      grafted OTCC, the baseline separations of polar molecules and proteins were
      obtained without peak tailing. The future work will focus on the further
      development of the glycopolymer brushes for the highly polar compound separation,
      such as glycans and glycoproteins.

PMID- 24432644
TI  - [Identification of traditional Chinese medicines by oligosaccharide
      electrophoresis analysis assisted with cluster analysis].
AB  - The structure of polysaccharide in traditional Chinese medicine (TCM) is complex
      and characteristic. A method of oligosaccharide electrophoresis analysis assisted
      with cluster analysis (CA) was established to simultaneously identify TCMs. Six
      TCMs from three families were selected as experimental subjects and their
      polysaccharides were extracted. The obtained oligosaccharides via incompletely
      degraded TCM polysaccharides were derivatized using 1-phenyl-3-methyl-5
      pyrazolone (PMP). The PMP-oligosaccharide derivatives were separated and analyzed
      by capillary zone electrophoresis (CZE). The six TCMs were identified by the
      featured information of oligosaccharide electropherograms with CA. The
      electrophoresis conditions were as follows: uncoated fused silica capillary
      column (49 cm/40 cm (total length/effective length) x 50 microm); running buffer
      solution, 50 mmol/L phosphate buffer solution (pH 2.5); detection wavelength, 245
      nm; operating voltage, 15 kV; hydrodynamic pressure injection, 10 cm x 4 s. The
      results showed that the six TCMs from three families were effectively identified
      by the method of TCM oligosaccharide electropherograms combined with CA. This
      method is a promising tool to identify TCM with good reliability and
      reproducibility.

PMID- 24432645
TI  - [Analysis of difference of proteins of gastric cancer tissue and adjacent normal
      tissue by capillary electrophoresis with laser-induced fluorescence detection].
AB  - Gastric cancer is one of the familiar malignant tumors in clinical study.
      Research on tumor biomarkers has increased noticeably in recent years. An
      experimental method of protein separation by capillary electrophoresis with laser
      induced fluorescence detection (CE-LIF) was established and improved. A series of
      effects on capillary electrophoresis (CE) were studied, such as the dynamic
      coating method of capillary, concentration of polyethylene oxide (PEO) as sieving
      medium, pH of running buffer, separation voltage, temperature and fluorescent
      dye. Then the optimized method was established for the determination of gastric
      cancer tissue and adjacent normal tissue. According to the analysis of the
      protein fingerprints, the results showed that the similarity of protein was up to
      0.8. The molecular masses of differential proteins were almost between 50,000 Da
      and 100,000 Da. It indicated that these proteins might be potential biomarkers
      for cancer diagnosis which may reduce the searching scope. By statistical
      analysis of histological classification and electrophoresis peak numbers, this
      method was demonstrated reliably, and had the potential for clinical
      applications.

PMID- 24432646
TI  - [Determination of antibiotic residues in manure by liquid chromatography-tandem
      mass spectrometry coupled with solid phase extraction].
AB  - A method was developed for the simultaneous determination of tetracyclines (TCs),
      quinolones (QUs) and sulfadimidine (SM2) in pig manure and chicken dung by a
      combined high performance liquid chromatography (HPLC) and tandem mass
      spectrometry (MS/MS) detection coupled with solid phase extraction. The residual
      antibiotics in manure were extracted with the mixture of methanol, acetic acid
      and water with the volume ratio of 6:3:1, enriched and purified by a hydrophilic
      lipophilic balance (HLB) solid-phase extraction cartridge. The C18
      chromatographic column was used to complete the separation of the analytes which
      were detected in multiple reaction monitoring (MRM) mode via positive
      electrospray ionization (ESI+). The external standard calibration curves were
      used for the quantification. All the antibiotics were determined with an
      excellent linear relationship from 50 to 1000 microg/L for TCs and QUs, and from
      5 to 100 microg/L for SM2. The limits of detection for TCs, QUs and SM2 were 0.25
      7.18, 0.15-3.16 and 0.04 microg/kg, respectively. The recoveries of TCs, QUs and
      SM2 in pig manure and chicken dung were 40%-124% at the spiked levels from 0.1 to
      10 microg/g (RSDs ranged from 3.0% to 9.5%, n = 6). The method was successfully
      applied to determine the antibiotics in pig manure and chicken dung samples. The
      method has high accuracy and sensitivity for the determination of TCs, QUs and
      SM2 in pig manure and chicken dung.

PMID- 24432647
TI  - [Determination of four plant growth regulator residues in amphisarcas by high
      performance liquid chromatography-tandem mass spectrometry].
AB  - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      method was developed for the determination of the plant growth regulator (PGR)
      (paclobutrazol, forchlorfenuron, isopentennyladenine and 6-benzylaminopurine)
      residues in amphisarcas. The sample was extracted with acetonitrile, then cleaned
      up by MCX solid phase extraction. The HPLC separation was performed on an Agilent
      XDB-C18 column with 5 mmol/L ammonium acetate solution and acetonitrile
      containing 0.1% (volume percentage) formic acid as the mobile phases in a
      gradient elution mode. The PGRs were determined by MS/MS in positive electrospray
      ionization mode, and quantified by matrix-matched external standard method. The
      calibration curves showed good linearity in each range with correlation
      coefficients greater than 0.999. The limits of quantification (LOQs, S/N > 10)
      were 0.04-1.35 g/kg and the limits of detection (LODs, S/N > 3) were 0. 01-0 41
      microg/kg for the four PGRs spiked in cucumber and apple. The recoveries of the
      four PGRs spiked at three levels ranged from 81.0% to 93.%, with the relative
      standard deviations (RSDs) of 3.5%-9.5%. The sensitivity, accuracy and precision
      of the method meet the technical standards of the pesticide determination.
      Therefore the method can be applied to the determination of the four PGRs in
      amphisarcas.

PMID- 24432648
TI  - [Simultaneous determination of 24 industrial dyes in grain and meat products by
      ultra performance liquid chromatography-tandem mass spectrometry].
AB  - An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS)
      analytical method was established for the simultaneous determination of 24
      forbidden industrial dyes in grain and meat products. The sample was extracted
      with methanol and acetonitrile, and cleaned-up by a WAX solid phase extraction
      column. The solution was separated on an ACQUITY UPLC BEH C18 column eluted with
      a mixture of 10 mmol/L ammonium acetate-0.2% formic acid aqueous solution and
      methanol-acetonitrile (7:3, v/v) as the mobile phases, and then analyzed in
      multiple reaction monitoring (MRM) mode. The correlation coefficients were above
      0.99, the average recoveries were 61%-116%, and the relative standard deviations
      (RSD, n = 6) were lower than 13%. The quantification limits were 0.1-4.0
      microg/kg. This method is simple, effective, sensitive, and suitable for the
      determination and confirmation of the 24 forbidden industrial dyes in grain and
      meat products.

PMID- 24432649
TI  - [Determination of phenolic and salicylanilide anthelmintics in liquid milk by
      high performance liquid chromatography].
AB  - An analytical method for the determination of nitroxynil, oxyclozanide, closantel
      and rafoxanide in liquid milk by high performance liquid chromatography (HPLC)
      has been established. The milk sample was extracted with acetonitrile containing
      1% (v/v) triethylamine. The supernatant was purified by an anion exchange solid
      phase extraction column. The analyte was detected by ultraviolet detector after
      the HPLC separation on a C18 RP column. The mobile phase was composed of
      acetonitrile-0.02 mol/L ammonium acetate solution with pH 4.0. The linear ranges
      of the four drugs in the spiked blank milk samples were 5-500 microg/kg, and the
      correlation coefficients were higher than 0.99. The limits of detection (LOD)
      were 3 microg/kg, and the limits of quantification (LOQ) were 5 microg/kg. The
      average recoveries and relative standard deviations (RSDs) of nitroxynil,
      oxyclozanide, closantel and rafoxanide at the spiked levels of 1/2MRL (maximum
      residue limit), MRL and 2MRL ranged from 92.20% to 96.13%, 5.55% to 16.30%;
      87.40% to 94.74%, 5.40% to 12.21%; 86.97% to 91.09%, 2.67% to 8.17%; and 77.86%
      to 95.36%, 5.02% to 13.15% respectively. The method is simple and sensitive for
      the quantification of phenolic and salicylanilide anthelmintics in liquid milk.

PMID- 24432650
TI  - [Preface for special issue on biobased chemicals (2013)].
AB  - Biobased chemicals are one of the main missions of bioeconomy. In this special
      issue, we reviewed the recent progress in the metabolic engineering and
      fermentation control study on biobased succinic acid, adipic acid, lactic acid, 3
      hydroxypropanoic acid, glucaric acid, glycerol, xylitol, higher alcohols and
      ethylene, recombinant construction for the direct utilization of lignocelluloses,
      biotransformation of bio-based lactic acid, and salting-out extraction of bio
      based chemicals. Some research articles on biobased succinic acid, D-mannitol,
      malic acid, 5-aminolevulinic acid, 1,3-propanediol, and butanol are also
      included.

PMID- 24432651
TI  - [Advances of consolidated bioprocessing based on recombinant strategy].
AB  - Lignocellulosic biomass represents an abundant, low-cost and renewable source of
      potentially fermentable sugars. It is acandidate besides petroleum as feedstock
      for fuel and chemical production. Recent researches on utilizing
      lignocellulosicsas feedstock boost development of numerous-promising processes
      for a variety of fuels and chemicals, such as biodiesel, biohydrogen and ethanol.
      However, high cost in depolymerization is a primary obstacle preventing the use
      of lignocellulosic biomass as feedstock. Consolidated bioprocessing (CBP), refers
      to the bioprocess without any exogenous cellulolyotic enzymes added, converting
      the lignocellulosic material into biochemicals directly, which could potentially
      avoid the cost of the dedicated enzyme generation step by incorporating enzyme
      generating, biomass-degrading and bioproduct-producing capabilities into a single
      organism through genetic engineering. There are two CBP strategies, native
      strategy and recombinant strategy. We mainly introduce the recombinant strategy,
      including its principle, the two responding styles, the contributions of
      synthetic biology and metabolic engineering and the future challenges.

PMID- 24432652
TI  - [Progress in engineering Escherichia coli for production of high-value added
      organic acids and alcohols].
AB  - Confronted with the gradual exhaustion of the earth's fossil energy resources and
      the grimmer environmental deterioration, the bio-based process to produce high
      value added platform chemicals from renewable biomass is attracting growing
      interest. Escherichia coli has been chosen as a workhouse for the production of
      many valuable chemicals due to various advantages, such as clear genetic
      background, convenient to be genetically modified and good growth properties with
      low nutrient requirements. Rational strain development of E. coli achieved by
      metabolic engineering strategies has provided new processes for efficiently
      biotechnological production of various high-value chemical building blocks. This
      review focuses on recent progresses in metabolic engineering of E. coli that lead
      to efficient recombinant biocatalysts for production of high-value organic acids
      such as succinic acid, 3-hydroxypropanoic acid and glucaric acid as well as
      alcohols like glycerol and xylitol. Besides, this review also discusses several
      other platform chemicals, including 2,5-furan dicarboxylic acid, aspartic acid,
      glutamic acid, itaconic acid, levulinic acid, 3-hydroxy-gamma-butyrolactone and
      sorbitol, which have not been produced by E. coli until now.

PMID- 24432653
TI  - [Biosynthesis of adipic acid].
AB  - Adipic acid is a six-carbon dicarboxylic acid, mainly for the production of
      polymers such as nylon, chemical fiber and engineering plastics. Its annual
      demand is close to 3 million tons worldwide. Currently, the industrial production
      of adipic acid is based on the oxidation of aromatics from non-renewable
      petroleum resources by chemo-catalytic processes. It is heavily polluted and
      unsustainable, and the possible alternative method for adipic acid production
      should be developed. In the past years, with the development of synthetic biology
      and metabolic engineering, green and clean biotechnological methods for adipic
      acid production attracted more attention. In this study, the research advances of
      adipic acid and its precursor production are reviewed, followed by addressing the
      perspective of the possible new pathways for adipic acid production.

PMID- 24432654
TI  - [Progress in microbial production of succinic acid].
AB  - Succinic acid is one of the key intermediates in the tricarboxylic acid cycle
      (TCA)and has huge potentials in biopolymer, food, medicine applications. This
      article reviews recent research progress in the production of succinic acid by
      microbial fermentation, including discovery and screening of the succinic-acid
      producing microbes, the progress of genetic engineering strategy and metabolic
      engineering technology for construction of succinic acid-producing strains, and
      fermentation process control and optimization. Finally, we discussed the
      limitation of current progress and proposed the future research needs for
      microbial production of succinic acid.

PMID- 24432655
TI  - [Recent developments in L-lactate fermentation by genetically modified
      microorganisms].
AB  - Lactic acid is an important platform chemical. Especially with rapid development
      of poly (lactic acid) industry, the demand for L-lactic acid is continuously
      increasing. To further reduce the fermentation costs and improve the robustness
      of strains from industrial point of view, many modern biotechnological approaches
      have been applied to strain development. In this review, we briefly summarize
      recent advances in L-lactate fermentation by genetically modified microorganisms,
      including lactic acid bacteria, yeast, E. coli and Rhizopus species.

PMID- 24432656
TI  - [Progress in biotransformation of bio-based lactic acid ].
AB  - Fermentative production of lactic acid, an important bio-based chemicals, has
      made considerable progress. In addition to the food industry and production of
      polylactic acid, lactic acid also can be used as an important platform chemical
      for the production of acrylic acid, pyruvic acid, 1,2-propanediol, and lactic
      acid esters. This article summarizes the recent progress in biocatalytic
      production of lactic acid derivatives by dehydration, dehydrogenation, reduction,
      and esterification. Trends in the biotransformation of lactic acid are also
      discussed.

PMID- 24432657
TI  - [Advance in producing higher alcohols by microbial cell factories].
AB  - Higher alcohols have a high energy density, low hygroscopicity and can be mixed
      with gasoline at any ratio. It is the trend to replace fossil fuels with biofuels
      produced via microbial fermentation of renewable resources. We reviewed the
      progress in the development of engineered Saccharomyces cerevisiae and
      Escherichia coli that can produce higher alcohols, as well as the related
      technology platforms. We mainly focused on the construction of CoA-dependent
      pathways and alpha-keto acid mediated non-fermentative pathways, analyzed their
      respective characteristics, and summarized the construction strategies. The
      problems to be solved and future research direction were also discussed.

PMID- 24432658
TI  - [Direct biosynthesis of ethylene].
AB  - Ethylene is the most widely used petrochemical feedstock globally. The
      development of bio-ethylene is essential due to limited fossil fuels and rising
      oil prices. Bio-ethylene is produced primarily by the dehydration of ethanol, but
      can alternatively be directly produced from ethylene biosynthesis pathways in
      plants, algae, or microorganisms by using cheap and renewable substrates. This
      review addressed the biosynthesis of ethylene in plants and microorganisms, the
      characterization of key enzymes, genetic engineering strategies for ethylene
      biosynthesis in microorganisms, and evaluated its perspective and successful
      cases toward the industrial application. The direct production of bio-ethylene
      from a biological process in situ is promising to supplement and even replace the
      petrochemical ethylene production.

PMID- 24432659
TI  - [Research progress in salting-out extraction of bio-based chemicals].
AB  - Bio-refinery using cheap biomass focuses mainly on strain improvement and
      fermentation strategies whereas less effort is made on down-stream processing.
      Using cheap biomass more impurities are introduced into the fermentation broths
      than mono-sugar substrate, thus down-stream processing for bio-based chemicals
      becomes the key problem in industrial production. The technique called salting
      out extraction (SOE) was introduced in this review, which is used to separate
      target products from fermentation broth on the basis of partition difference of
      chemicals in two phases formed by mixing salts and organic solvents (or
      amphipathic chemicals) with broth at suitable ratios. The effect of solvents and
      salts on the formation of two aqueous phases, especially short chain alcohols and
      inorganic salts, and the application of SOE in recovery of bio-based chemicals,
      such as lactic acid, 1,3-propanediol, 2,3-butanediol and acetoin were summarized.
      The bio-chemicals were efficiently recovered from fermentation broth, and most of
      the impurities (cells and proteins) were removed in the same step. This technique
      is promising in the separation of bio-based chemicals, especially the recovery of
      hydrophilic molecules with low molecular weights.

PMID- 24432660
TI  - [Production of D-mannitol by metabolically engineered Escherichia coli].
AB  - D-Mannitol has wide applications in food, pharmaceutical, and chemical
      industries. In this study, we constructed a genetically stable Escherichia coli
      strain for D-mannitol production by integrating mannitol dehydrogenase (mdh) and
      fructose permease (fupL) genes of Leuconostoc pseudomesenteroides ATCC 12291 into
      chromosome of E. coli ATCC 8739 and inactivating other fermentation pathways
      (including pyruvate formate-lyase, lactate dehydrogenase, fumarate reductase,
      alcohol dehydrogenase, methylglyoxal synthase and pyruvate oxidase). Using
      mineral salts medium with glucose and fructose as carbon sources, the engineered
      strain could produce 1.2 mmol/L D-mannitol after anaerobic fermentation for 6
      days. Based on the coupling of cell growth and D-mannitol production, metabolic
      evolution was used to improve D-mannitol production. After evolution for 80
      generations, D-mannitol titer increased 2.6-fold and mannitol dehydrogenase
      activity increased 2.8-fold. Genetically stable strains constructed in this work
      could ferment sugars to produce D-mannitol without the addition of antibiotics,
      inducers and formate, which was favorable for industrial production.

PMID- 24432661
TI  - [Effects of furfural and 5-hydroxymethylfurfural on succinic acid production by
      Escherichia coli].
AB  - Succinic acid production by fermentation from biomass, especially the
      lignocellulosic hydrolysate, is an alternative to chemical synthesis. Many
      studies report the inhibition of cell growth and succinic acid production from
      lignocellulosic hydrolysate, hardly is known about the actual kinetic and
      mechanism of the inhibition of individual factors. In this study, we studied
      inhibition effects of furfurals and 5-hydroxymethylfurfural (5-HMF) on cell
      growth and succinic acid production of engineered E. coli. Cell growth and
      succinic acid titer were severely inhibited by furfural and HMF with both
      concentrations higher than 0.8 g/L. Cell growth was totally inhibited when the
      concentration of furfural was above 6.4 g/L, or the concentration of HMF was
      above 12.8 g/L. At the concentration of maximum toleration, which was 3.2 g/L,
      furfural decreased the cell mass by 77.8% and the succinic acid titer by 36.1%.
      HMF decreased the cell mass by 13.6% and the succinic acid titer by 18.3%.
      Activity measurements of key enzymes revealed that phosphoenolpyruvate
      carboxylase, malate dehydrogenase, fumarate reductase all were inhibited by
      furfural and HMF. This study gave a quantitative view to the succinic acid
      production under the inhibition of lignocellulose degradation products and will
      help overcome the difficulties of the lignocellulosic hydrolysate fermentation.

PMID- 24432662
TI  - [Optimization of succinic acid fermentation with Actinobacillus succinogenes by
      response surface methodology].
AB  - Succinic acid is an important C4 platform chemical in the synthesis of many
      commodity and special chemicals. In the present work, different compounds were
      evaluated for succinic acid production by Actinobacillus succinogenes GXAS 137.
      Important parameters were screened by the single factor experiment and Plackeet
      Burman design. Subsequently, the highest production of succinic acid was
      approached by the path of steepest ascent. Then, the optimum values of the
      parameters were obtained by Box-Behnken design. The results show that the
      important parameters were glucose, yeast extract and MgCO3 concentrations. The
      optimum condition was as follows (g/L): glucose 70.00, yeast extract 9.20 and
      MgCO3 58.10. Succinic acid yield reached 47.64 g/L at the optimal condition.
      Succinic acid increased by 29.14% than that before the optimization (36.89 g/L).
      Response surface methodology was proven to be a powerful tool to optimize
      succinic acid production.

PMID- 24432663
TI  - [Construction and fermentation control of reductive TCA pathway for malic acid
      production in Saccharomyces cerevisiae].
AB  - Malic acid is widely used in food, and chemical industries. Through
      overexpressing pyruvate carboxylase and malate dehydrogenase in pdc1-deficient
      Saccharomyces cerevisiae, malic acid was successfully produced through the
      reductive TCA pathway. No malic acid was detected in wild type Saccharomyces
      cerevisiae, however, 45 mmol/L malic acid was produced in engineered strain, and
      the concentration of byproduct ethanol also reduced by 18%. The production of
      malic acid enhanced 6% by increasing the concentration of Ca2+. In addition, the
      final concentration reached 52.5 mmol/L malic acid by addition of biotin. The
      increasing is almost 16% higher than that of the original strain.

PMID- 24432664
TI  - [Deficiency of succinic dehydrogenase or succinyl-coA synthetase enhances the
      production of 5-aminolevulinic acid in recombinant Escherichia coli].
AB  - 5-aminolevulinic acid (ALA), a precursor for biosynthesis of pyrrole compounds in
      living organisms, has been widely used in agriculture and medical photodynamics
      therapy and is regarded as a promising value-added bio-based chemical. In the
      previous investigations on ALA production with recombinant Escherichia coli
      expressing heterogenous C4 pathway gene, LB media supplemented with glucose and
      ALA precursors succinate and glycine is widely used, leading to high production
      cost. Succinate participates in ALA biosynthesis in a form of succinyl-CoA. In
      this study, genes involved in succinyl-CoA consumption, sdhAB (encoding succinic
      dehydrogenase) or sucCD (encoding succinyl-CoA synthetase) of E. coli MG1655 was
      knocked out and tested for ALA accumulation. In comparison with the recombinant
      E. coli strain expressing heterogenous ALA synthetase, the sdhAB- or sucCD
      deficient strain accumulate 25.59% and 12.40%, respectively, more ALA in a 5 L
      fermentor using a defined synthetic medium with glucose as main carbon source and
      without supplementation of succinate, providing a novel cost-effective approach
      for industrial production of ALA.

PMID- 24432665
TI  - [Construction of polyhydroxybutyrate pathway in Klebsiella pneumoniae].
AB  - 1,3-propanediol production with the byproduct of biodiesel production is
      important to increase the economic benefit of biodiesel industry. Accumulation of
      3-hydroxypropionaldehyde is one of the key problems in the 1,3-propanediol
      fermentation process, leading to the cell death and the fermentation abnormal
      ceasing. Different from the traditional way of reducing the accumulation of the 3
      hydroxypropionaldehyde, we introduced the polyhydroxybutyrate pathway into the
      Klebsiella pneumoniae for the first time to enhance the tolerance of K.
      pneumoniae to 3-hydroxypropionaldehyde, at the same time, to improve the 1,3
      propanediol production. Plasmid pDK containing phbC, phbA, phbB gene was
      constructed and transformed into K. pneumoniae successfully. PHB was detected in
      the engineered K. pneumoniae after IPTG induction and its content enhanced with
      the IPTG concentration increasing. The optimized IPTG concentration was 0.5
      mmol/L. The constructed K. pneumoniae could produce 1,3-propanediol normally, at
      the same time accumulate polyhydroxybutyrate. With the constructed strain, the
      fermentation proceeds normally with the initial glucose was 70 g/L which the wild
      type strain stopped growing and the fermentation was ceasing; 1,3-propanediol
      concentration and yield reached 31.3 g/L and 43.9% at 72 h. Our work is helpful
      for the deep understanding of 1,3-propanediol metabolic mechanism of Klebsiella
      pneumoniae, and also provides a new way for strain optimization of Klebsiella
      pneumoniae.

PMID- 24432666
TI  - [Butanol production from corn stover hydrolysate with in-situ liquid-liquid
      extraction].
AB  - Butanol production from corn stover hydrolysates (CSH) with in-situ liquid-liquid
      extraction was studied to enhance the production and reduce the fermentation
      cost. Oleyl alcohol was selected as the suitable solvent and added at the initial
      fermentation time with the ratio of 1:1 (oleyl alcohol: fermentation broth, V/V).
      Under this condition, butanol and ABE from CSH with 32.1 g/L total sugars were
      3.28 and 4.72 g/L, which were 958.1% and 742.9% higher than those of the
      controls, respectively. Butanol and ABE production from CSH of 49.7 g/L total
      sugars after detoxification by ion exchange resin D301 coupled with extraction
      fermentation were 10.34 g/L and 14.72 g/L with an ABE yield of 0.31 g/g (g ABE/g
      utilized sugar), which were equal to those of glucose and xylose mixture
      fermentation. The detoxification and extraction fermentation technology of
      cellulosic butanol production would provide a crucial technical support to the
      industrialized production of cellulosic butanol.

PMID- 24432667
TI  - [Progress in researches on ancient history of atherosclerosis].
AB  - Atherosclerosis has been thought to be a disease of modern society, and its
      occurrence was closely related to contemporary diet and lifestyle. However, a
      series of investigations on ancient mummies by autopsy and CT scan concluded that
      atherosclerosis was commonly seen in ancient times. The presence of
      atherosclerosis in ancient human beings suggested that aging and genetic
      predisposition might be essential risk factors for atherosclerosis.

PMID- 24432668
TI  - [Exploration of reversion and Chinese medical treatment of precancerous lesion of
      gastric cancer].

PMID- 24432669
TI  - [Clinical effect analysis of ankylosing spondylitis treated by Chinese medical
      syndrome differentiation].
AB  - OBJECTIVE: To evaluate the curative effect and safety of Bushen Qiangji Decoction
      (BQD) and Qingre Qiangji Decoction (QQD) in treating ankylosing spondylitis (AS)
      patients, and to verify the clinical utility of AS syndrome differentiation and
      treatment scheme [Shen-deficiency induced stasis obstruction syndrome (SDISOS)
      and dampness-heat obstruction syndrome (DHOS) being two basic syndrome types,
      Shen invigorating blood activating method (SIBAM) and heat clearing dampness
      resolving method (HCDRM) being two basic treatment methods]. METHODS: Totally 354
      AS patients of SDISOS and DHOS were randomly assigned to the treatment group and
      the control group using a multi-center randomized, positive drug parallel
      controlled clinical trail. Patients in treatment group were treated by BQD or QQD
      according to syndrome typing, while those in the control group took Sulfasalazine
      enteric-coated tablet (SECT), 24 weeks as one therapeutic course. After
      treatment, the clinical efficacy was evaluated by using ASAS20 standard (set by
      Asessment in Ankylosing Spondylitis working group), Chinese medical efficacy
      evaluation standards, and BASDAI, BASFI, BASMI, night-pain index, spinal pain
      index, PGA, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
      RESULTS: After 24 weeks of treatment by BQD or QQD, ASAS20 standard rate was
      86.75% in the treatment group, and the total effective rate of Chinese medical
      syndrome was 85.47%. They could significantly reduce patients' integrals of
      Chinese medical syndrome, BASDAI, BASFI, BASMI, night-pain index, spinal pain
      index, and PGA (all P < 0.01). CONCLUSIONS: QQD and BQD got confirmable clinical
      effects in treating AS, providing strong evidence of evidence-based medicine for
      syndrome differentiation and treatment of AS.

PMID- 24432670
TI  - [Treatment of severe active systemic lupus erythematosus by PMC therapy combined
      langchuang fuzheng jiedu capsule: a clinical observation].
AB  - OBJECTIVE: To evaluate the efficacy and safety of PMC therapy (Prednisone,
      Methotrexate, Chloroquine) combined Langchuang Fuzheng Jiedu Capsule (LFJC), thus
      choosing a better therapy of integrative medicine for SLE in the period of
      glucocorticoid use. METHODS: Sixty active SLE patients were randomly assigned to
      two groups, the control group and the treatment group. Those in the control group
      received PMC therapy (As for Prednisone, it was given at the daily dose of 1
      mg/kg till 2 weeks after the condition being stable or after 8 weeks of
      treatment. Then the dose was reduced by 10% every two weeks. When the dose was
      reduced to 0.5 mg/kg daily, it was reduced by 2.5 mg per two weeks. When the dose
      was reduced to 15 mg daily, the dose was reduced to 2.5 mg per four weeks. As for
      Methotrexate, 10 mg each time, once a week. As for Chloroquine, 100 mg each time,
      twice daily), while those in the treatment group received PMC therapy (the same
      way as that for the control group) combined with LFJC (consisting of Astragalus
      membranaceus 50 g, Angelica sinensis 20 g, Ligusticum Chuanxiong 20 g, prepared
      Rehmannia Rhizome 30 g, Herba Serissae 30 g, Centella 30 g, centipede 4 g,
      scorpions 10 g, nidus versace 12 g, et al., 0.5 g per pill, containing 5.7 g
      crude drug. When the hormone was given at a large dose, LFJC was administered at
      12 pills each time, three times daily). When the hormone was given at a middle
      dose, LFJC was administered at 8 pills each time, three times daily. When the
      hormone was given at a small dose, LFJC was administered at 6 pills each time,
      three times daily. The treatment course was six months. The improvement of
      symptoms and signs between before and after treatment, SLE disease activity index
      (SLEDAI), efficacy of Chinese medical syndrome, UPro quantitation, erythrocyte
      sedimentation rate (ESR), complement 3 (C3), C-reactive protein (CRP), the
      reduction and withdrawal of hormones, and infection of the respiratory tract were
      observed. RESULTS: The difference in post-SLEDAI was obviously larger in the
      treatment group than in the control group (P < 0.05). The fatigue severity scale
      (FSS) was less after treatment than before treatment in the treatment group,
      showing statistical difference when compared with that of the control group (P <
      0.05). The total effective rate was 93.33% in the treatment group, showing
      statistical difference when compared with that of the control group (86.66%; chi2
      = 6.736, P < 0.05). The ESR decreased after treatment in the treatment group,
      showing statistical difference when compared with that of the control group (P <
      0.01). C3 increased after treatment in the treatment group, showing statistical
      difference when compared with that of the control group (P < 0.05). The hormone
      was reduced to (13.70 +/- 5.42) mg/d by the end of the therapeutic course in the
      treatment group, obviously less than that of the control group [(17.63 +/- 7.80)
      mg/d, P < 0.05). Seven patients suffered from secondary infection of the
      respiratory tract infection in the treatment group (5 from upper respiratory
      tract infection and 2 from lower respiratory tract infection), obviously less
      than those of the control group (25 from upper respiratory tract infection and 10
      from lower respiratory tract infection) (P < 0.05). CONCLUSIONS: PMC combined
      LFJC was a better treatment program for severe active SLE (SLEDAI > or = 15). It
      was more safe and effective when compared with using Western medicine alone. It
      could enhance the efficacy of hormones and help reduction/withdrawal of hormones.

PMID- 24432671
TI  - [Treatment of rheumatoid arthritis arthralgia by xiaoyan zhitong paste: a
      clinical observation].
AB  - OBJECTIVE: To formulate a comprehensive treatment program for rheumatoid
      arthritis arthralgia by clinical observing the efficacy of Xiaoyan Zhitong Paste
      (XZP). METHODS: Adopted was stratified, block randomized, double-blinded, placebo
      parallel controlled method. Subjects were assigned to the treatment group and the
      placebo group. Those in the treatment group were treated by external application
      of XZP, one to two pastes each time, covering the painful area, exchange once per
      24 h, with one-day interval during a 7-day consecutive medication, two 7-days of
      treatment consisting of one therapeutic course. XZP placebos were applied for
      those in the placebo group in the same medication way. Joint pain and VAS were
      taken as main indices for observing the clinical efficacy of XZP. RESULTS: The
      improvement of the analgesic effect and the Chinese medical syndrome efficacy of
      XZP were superior to that of the placebo. CONCLUSION: XZP showed obvious effect
      in treating rheumatoid arthritis arthralgia with no obvious adverse reaction.

PMID- 24432672
TI  - [Comparative analysis of clinical indicators of gout patients of different
      syndrome types and its significance].
AB  - OBJECTIVE: To understand the difference in clinical indicators of gout patients
      of different Chinese medical syndromes and its clinical significance. METHODS:
      Form November 2011 to December 2012, syndrome typed were 257 male gout in
      /outpatients from Affiliated Hospital of Chuanbei Medical College. Another 50
      healthy male subjects were recruited as the control. Their clinical and
      laboratory data were collected. All were excluded from infections and other
      inflammatory diseases. RESULTS: Four syndrome types existed in gout patients,
      i.e., intermingled phlegm-stasis blood syndrome (IPSBS), obstruction of dampness
      and heat syndrome (ODHS), Pi-deficiency induced dampness syndrome (PDIDS), qi
      blood deficiency syndrome (QBDS). Of them, 53 acute phase gout patients suffered
      from IPSBS, 41 from ODHS, 25 from QBDS, and 17 from PDIDS; 41 non-acute phase
      gout patients suffered from QBDS, 40 from PDIDS, 24 from ODHS, and 16 from IPSBS.
      Statistical analysis of clinical data showed that, when compared with the normal
      control group, there was statistical difference in blood routines (WBC, GR, LY,
      MO) and blood biochemical indices (UA, Ur, Cr, ALT, AST, ALB, GLOB, TG, HDL-C,
      VLDL-C, apoA, apoB100) of gout patients of different syndromes (P < 0.05, P <
      0.01). There was also statistical difference or correlation among different
      syndromes (P < 0.05). CONCLUSIONS: In the acute phase gout patients, IPSBS and
      ODHS were dominated, while in the non-acute phase gout patients, QBDS and PDIDS
      were often seen. In patients of IPSBS and ODHS, inflammation and immune response
      were more obvious, indicating that better efficacy might be achieved by clearing
      heat and removing blood stasis associated anti-inflammatory and immune regulation
      therapies. In patients of QBDS and PDIDS, impaired renal functions were more
      significant, indicating that better efficacy might be achieved by invigorating Pi
      and tonifying Shen dominated treatment.

PMID- 24432673
TI  - [Treatment of upper respiratory infection by fangfeng tongsheng granule: a
      randomized controlled study].
AB  - OBJECTIVE: To evaluate the clinical effectiveness and safety of Fangfeng
      Tongsheng Granule (FTG) in the treatment of upper respiratory infection
      (superficial cold and interior heat syndrome, exterior and interior excess
      syndrome). METHODS: A randomized, double-blinded, multi-centered, placebo
      parallel-controlled clinical trial was adopted. Totally 324 patients were
      enrolled and assigned to two groups, 216 patients in the treatment group and 108
      patients in the control group. Those in the treatment group took FTG at the daily
      dose of 3 g, twice per day, the therapeutic course being 3 days. Those with
      axillary temperature more than 37 degrees C took one more time before medication.
      Those in the control group took simulated agent granules the same dose and dosage
      as the treatment group. The effect of Chinese medical syndrome (ECMS), the rate
      of temperature-dropping-to-normal (RT), the time of temperature-dropping-to
      normal (TT), the curative effect of single symptom (CESS) and adverse reactions
      were observed. RESULTS: Totally 203 completed the trial in the treatment group
      and 101 in the control group. In the treatment group, the cured-effective rate
      was 55.67% (113/ 101), the total effective rate was 93.10% (189/101), the ECMS
      score decreased by 9.24 +/- 4.46, while they were 5.94% (6/101), 36.63% (37/101),
      and 3.27 +/- 3.29, respectively in the control group (P < 0.01). The RT was
      87.50% (98/112) in the treatment group and 58.49% (31/53) in the control group (P
      < 0.01). The TT in the treatment group was superior to that of the control group
      (P < 0.01). As for CESS, all of the three primary symptoms and nine secondary
      symptoms were improved more obviously in the treatment group than in the control
      group. The integral decreased obviously, showing statistical difference (P <
      0.01). The decrease was more obvious in the treatment group than in the control
      group (P < 0.01). There was no adverse event related to FTG. CONCLUSION: FTG was
      effective and safe in treating upper respiratory infection (superficial cold and
      interior heat syndrome, exterior and interior excess syndrome).

PMID- 24432674
TI  - [Treatment of premature ovarian failure patients by bushen tiaojing recipe
      combined hormone replacement therapy: a clinical observation].
AB  - OBJECTIVE: To observe the clinical effect on treatment of premature ovarian
      failure (POF) patients by Bushen Tiaojing Recipe (BTR) and hormone replacement
      therapy (HRT). METHODS: Totally 72 POF patients were randomly assigned to three
      groups by random digit table, i.e., the Chinese medicine group, the Western
      medicine group, and the integrative medicine group, 24 in each group. Those in
      the Chinese medicine group took BTR. Those in the Western medicine group were
      treated by HRT. Those in the integrative medicine group were treated by BTR +
      HRT. All were treated for three courses and followed-up for 3 months after
      treatment. The clinical efficacy, integrals of clinical symptoms, and serum sex
      hormones levels [follicular stimulating hormone (FSH), estradiol (E2),
      luteinizing hormone (LH)] were compared among the three groups before treatment,
      at the end of treatment, and 3 months after withdrawal. RESULTS: (1) The total
      effective rate was better in the integrative medicine group than in the Chinese
      medicine group and the Western medicine group (P < 0.05). (2) At the end of
      treatment, the integrals of clinical symptoms decreased in the 3 groups when
      compared with before treatment in the same group (P < 0.05, P < 0.01). The
      integrals of clinical symptoms were higher at 3 months after withdrawal than at
      the end of treatment in the Western medicine group (P < 0.05). But there was no
      statistical difference in changes of integrals between the Chinese medicine group
      and the integrative medicine group (P > 0.05). (3) By the end of treatment serum
      E2 increased (P < 0.01), FSH and LH decreased (P < 0.01) in the three groups,
      more significantly in the integrative medicine group and the Western medicine
      group (P < 0.05, P < 0.01). At 3 months after withdrawal serum E2 decreased, FSH
      and LH increased in the Western medicine group, showing statistical difference
      when compared with the other two groups (P < 0.05, P < 0.01). There was no
      statistical difference in changes of serum E2, FSH, or LH between the Chinese
      medicine group and the integrative medicine group (P > 0.05). CONCLUSIONS: BTR
      combined HRT had significant effect on treatment of POF, could significantly
      improve patients' clinical symptoms, menstrual states, and serum sex hormones
      levels. It had lower recurrence rate. Patients suffered from less adverse
      reactions.

PMID- 24432675
TI  - [Effect of ruji recipe on the post-surgical survival of female breast cancer
      patients].
AB  - OBJECTIVE: To observe the effect of Ruji Recipe (RR) in preventing disease
      recurrence/metastasis and improving quality of life (QOL) for female breast
      cancer patients after operation. METHODS: Totally 102 female patients with stage
      I - III breast cancer were retrospectively analyzed. They were assigned to the
      treatment group (54 cases) and the control group (48 cases) according to whether
      they would rather accept RR therapy. Estrogen receptor/progesterone receptor
      (ER/PR) positive patients also accepted endocrine therapy. The overall survival
      (OS), disease-free survival (DFS), recurrence and metastasis, and QOL were
      compared between the two groups. RESULTS: Totally 100 patients completed the
      study. The median follow-up was 59 months. The median OS was 60 months in the
      treatment group and 52.5 months in the control group (chi2 = 3.274, P > 0.05).
      The median DFS was 55.0 months in the treatment group and 47.5 months in the
      control group (chi2 = 10.145, P < 0.01). The DFS rate was 75.9% (41/54) in the
      treatment group and 54.3% (25/46) in the control group (chi2 = -2.259, P < 0.05).
      There was statistical difference in the 2-, 3-, and 5-year DFS between the two
      groups (P < 0.01). There was statistical difference in the 2-year DFS 3-year DFS
      between stage II and III and stage III (P < 0.05, P < 0.01). There was
      statistical difference in the ER positive patients between 2-year DFS and 3-year
      DFS (P < 0.01, P < 0.05). There was statistical difference in the 3-and 5-year
      distant metastasis rate (DMR) in the treatment group, lower than that of the
      control group (3.7% vs 31.0%, 20.7% vs 60.7%; P < 0.01). By the end of follow-up,
      disease progression occurred in 13 cases of the treatment group, local recurrence
      in 3 cases, single organ metastasis in 7 cases, multi-metastasis in 3 cases,
      while the corresponding numbers were 21, 1, 11, and 9 in the control group (P <
      0.05). As for 1 week before study and at 2-year follow-up using Functional
      Assessment of Cancer Therapy for Breast Cancer (FACT-B) system, there was
      statistical difference in the QOL between the two groups (P < 0.05), and better
      effect was obtained in the treatment group. CONCLUSION: RR, as an assistant
      therapy, could improve the OS rate, the DFS rate, and the QOL for post-surgical
      female breast cancer patients in 2 -3 years.

PMID- 24432676
TI  - [Anti-depressive effect of acupuncture on selective serotonin reuptake
      inhibitors].
AB  - OBJECTIVE: To evaluate anti-depressive effects of acupuncture on selective
      serotonin reuptake inhibitors (SSRIs). METHODS: Totally 60 patients with
      depression were randomly assigned to the control group (30 cases) and the
      treatment group (30 cases). All patients took one kind of SSRIs. Those in the
      treatment group were additionally treated by acupuncture. All were treated for 6
      weeks. Patients' efficacies were evaluated with Hamilton Depression Scale (HAMD),
      Self-rating Depression Scale (SDS), and Eisenberg antidepressant side effects
      scale (Asberg). RESULTS: Compared with the control group after 6 weeks of
      treatment, the cured-markedly effective rate was improved by 33.4% in the
      treatment group (P < 0.05). The HAMD was lower in the treatment group. The
      tendency of interaction of sleep disorder factor and anxiety/somatization factor
      was different between at the end of 1-week treatment and at the end of 6-week
      treatment in the treatment group (P < 0.05). The SDS score decreased at the end
      of 6-week treatment in the treatment group. The reduction rate was elevated by
      19.23% (P < 0.05). By the end of 6-week treatment, the average score of Asberg
      decreased by 3.77 score in average in the treatment group, while it decreased by
      0.07 score in average in the control group (P < 0.05). CONCLUSION: Acupuncture
      could effectively improve anti-depressive effects of SSRIs and reduce their
      adverse reactions.

PMID- 24432677
TI  - [Effect of needling at waiguan (SJ5) on brain glucose metabolism in patients with
      cerebral infarction].
AB  - OBJECTIVE: To observe changes of brain glucose metabolism by needling at Waiguan
      (SJ5) in cerebral infraction (CI) patients using 18F-fluorodeoxyglucose (FDG)
      positron-emission computer tomography (PET/CT), thus exploring its effect and
      mechanisms. METHODS: A total of 21 patients with CI were recruited in this study.
      The location of lesion was limited to the left basal ganglia by CT or MRI scan.
      All patients were randomly assigned to three groups. i.e., the acupoint group
      (Group A), the non-acupoint group (Group B), the blank control group (Group C), 7
      in each group. Patients in Group A were needled at right Waiguan (SJ5). Those in
      Group B were needled at non-acupoint [10 mm beside Waiguan (SJ5)], whereas those
      in Group C did not receive any treatment. All patients underwent PET/CT head
      scan. All data were statistically analyzed using SPSS 13.0 Software and SPM8
      Software. RESULTS: Compared with Group C, glucose metabolism increased in
      bilateral superior temporal gyrus (BA38), right superior frontal gyrus (BA9),
      left cingulate gyrus (BA24), left culmen and pyramid of cerebellum, and right
      cerebellar tonsil of cerebellum in Group A. Compared with Group C, glucose
      metabolism increased in bilateral superior frontal gyrus (BA6, BA9, BA10),
      bilateral middle frontal gyrus (BA6, BA10), left middle frontal gyrus (BA4),
      bilateral uncus of limbic lobe (BA36, BA38), left cingulate gyrus (BA24, BA31),
      left posterior cingulate gyrus (BA30), left precuneus (BA7), left inferior
      parietal lobule (BA4), and left lingual gyrus of occipital lobe (BA18) in Group
      B. Compared with Group B, glucose metabolism increased in bilateral superior
      temporal gyrus (BA22, BA38), right inferior frontal gyrus (BA47), left culmen and
      cerebellar tonsil of cerebellum in Group A. Activated encephalic regions of
      needling at Waiguan (SJ5) were mainly dominated in the healthy side, bilateral
      superior temporal gyrus, and right inferior frontal gyrus. Activated encephalic
      regions of cerebellum were located at the left cerebellar hemisphere, left culmen
      of anterior cerebella lobe, and bilateral cerebellar tonsil of posterior
      cerebella lobe. CONCLUSIONS: Needling at Waiguan (SJ5) of CI patients induced
      increased glucose metabolism in local cerebral regions. Functional neuroimaging
      using PET/CT could directly reflect changes of brain glucose metabolism by
      acupuncture.

PMID- 24432678
TI  - [Observation of serum protein fingerprinting in primary liver cancer patients of
      different Chinese medical syndromes before and after interventional treatment].
AB  - OBJECTIVE: To explore changes of serum protein fingerprinting in primary liver
      cancer (PLC) patients of different Chinese medical syndromes before and after
      interventional treatment detected by surface enhanced laser desorption ionization
      time of flight mass spectrometry (SELDI-TOF-MS). METHODS: Totally 154 PLC
      patients were assigned to 5 groups, i.e., Gan depression syndrome (GDS, 37
      cases), Pi deficiency syndrome (PDS, 45 cases), dampness heat syndrome (DHS, 18
      cases), blood stasis syndrome (BSS, 28 cases), yin deficiency syndrome (YDS, 26
      cases). The mass spectra of serum proteins was analyzed by using SELDI-TOF-MS.
      Then the correlation between Chinese medical syndrome types and the mass spectra
      of serum proteins was explored before and after interventional treatment.
      RESULTS: Compared with the healthy control group, the expression of serum
      proteins peak was down-regulated in GDS with M/Z being 6 589 and 4 182 Da, in DHS
      with M/Z being 5 710 Da, in YDS with M/ Z being 6 992 Da, while it was up
      regulated in PDS with M/Z being 5 816 Da and in BSS with M/Z being 4 297 Da,
      showing statistical difference (P < 0.01). Compared with before intervention, the
      expression of serum proteins peak was down-regulated in GDS with M/Z being 6 589
      and 4 182 Da, in PDS with M/Z being 5 816 Da, in DHS with M/Z being 5 710 Da in
      BSS with M/Z being 4 297 Da, while it was up-regulated in YDS with M/Z being 6
      992 Da, showing statistical difference (P < 0.05, P < 0.01). CONCLUSION: There
      was statistical difference in changes of serum protein fingerprinting in PLC
      patients of different Chinese medical syndromes before and after interventional
      treatment.

PMID- 24432679
TI  - [Huoxue anxin recipe alleviated peroxidation damage of acute myocardial
      infarction rats by regulating iNOS/eNOS imbalance: an experimental research].
AB  - OBJECTIVE: To study the protective mechanism of Huoxue Anxin Recipe (HAR) on
      peroxidation damage of acute myocardial infarction (AMI) rats. METHODS: The AMI
      rat model was established by occluding the left anterior descending coronary
      artery. Compound Danshen Dripping Pill (CDDP) was used as the positive control.
      CDDP and HAR were administered to rats for 7 successive days since modeling. The
      heart function was detected using color Doppler echocardiography. Activities of
      induced nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS),
      total superoxide dismutase (tSOD) activity, and contents of malondialdehyde (MDA)
      were detected by ultraviolet spectrophotometer method. RESULTS: Compared with the
      sham-operation group, ejection fraction (EF) and fraction shortening (FS) rate
      significantly decreased in the model group (P < 0.01). Compared with the model
      group, EF and FS rate significantly increased in the HAR group, showing
      statistical difference (P < 0.05). There was no statistical difference in
      activities of serum iNOS, eNOS, or tSOD among all groups (P > 0.05). Compared
      with the sham-operation group, iNOS activities and MDA contents significantly
      increased in the myocardial tissue of the model group (P < 0.01), activities of
      eNOS and tSOD significant decreased (P < 0.01). Compared with the model group,
      iNOS activities in the myocardial tissue, MDA contents both in serum and the
      myocardial tissue significantly decreased (P < 0.05), activities of eNOS and tSOD
      significantly increased in the HAR group (P < 0.05). There was no statistical
      difference in each index between the CDDP group and the HAR group (P > 0.05).
      CONCLUSIONS: HAR could significantly improve cardiac functions of AMI rats. Its
      roles might be associated with regulating imbalanced iNOS/eNOS expressions and
      alleviating peroxidation damage of the myocardial tissue.

PMID- 24432680
TI  - [Effect of electroacupuncture at fenglong (ST40) on expressions of inflammatory
      factors in macrophages of hyperlipidemia model rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at Fenglong (ST40) on
      inflammatory factors in macrophages of hyperlipemia (HLP) rats, and to explore
      the role of EA in treating HLP. METHODS: Totally 50 adult male SD rats were
      selected. After one-week adaptative feeding, they were randomly divided into 5
      groups, i.e., the blank control group (Group A), the model group (Group B), the
      diet control group (Group C), the EA group (Group D), the diet control + EA group
      (Group E), 10 in each group. By the end of treatment, all rats were sacrificed to
      get blood from the carotid artery. The contents of serum total cholesterol (TC),
      triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density
      lipoprotein cholesterol (LDL-C) were determined. Peritoneal macrophages were
      isolated. Contents of intercellular adhesion molecule-1 (ICAM-1), monocyte
      chemoattractant protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), and
      interleukin 6 (IL-6) were detected using flow cytometry (FCM) after adding the
      fluorescein-labeled molecule antibodies of inflammatory factors. RESULTS:
      Compared with Group A, the serum contents of TC and LDL-C obviously increased and
      HDL-C significantly decreased in Group B (all P < 0.01). There was no obvious
      change in the content of TG between Group A and Group B (P > 0.05). Compared with
      Group B, the contents of TC and LDL-C significantly decreased in Group C, D, and
      E (P < 0.01). Compared with Group C, serum contents of TC and LDL-C obviously
      decreased in Group D and E (P < 0.01). Compared with Group B, the content of
      macrophages significantly increased in Group A (P < 0.01). Compared with Group B,
      the content of macrophages significantly decreased in Group D and E (P < 0.01),
      more obviously in Group E (P < 0.01). Compared with Group C, the content of
      macrophages significantly decreased in Group E (P < 0.05). Compared with Group A,
      levels of ICAM-1, MCP-1, TNF-alpha, and IL-6 in the peritoneal macrophages
      significantly increased in Group B (P < 0.01). Compared with Group B, levels of
      ICAM-1, MCP-1, TNF-alpha, and IL-6 significantly decreased in Group C, D, and E,
      but more obviously in Group E (P < 0.01). Compared with Group C, levels of ICAM
      1, MCP-1, TNF-alpha (P < 0.05, P < 0.01), and IL-6 (P < 0.05) significantly
      decreased in Group E. CONCLUSION: EA at Fenglong (ST40) could obviously
      downregulate the serum levels of TC and LDL-C in HLP rats, reduce the contents of
      macrophages, ICAM-1, MCP-1, TNF-alpha, and IL-6, thus arriving at the therapeutic
      effect in treating HLP.

PMID- 24432681
TI  - [Effect of acupuncture on the p53 protein expression of mice with Alzheimer's
      disease].
AB  - OBJECTIVE: To observe the effect of acupuncture method for benefiting qi,
      regulating blood, supplementing the root, and cultivating the essence (BQRBSRCE)
      on the p53 protein expression of mice with Alzheimer's disease (AD). METHODS:
      SAMP8 mice were divided into the control group, the acupuncture group, and the
      non-acupoint group. The homologous SAMR1 control group was set up. Mice in the
      acupuncture group used acupuncture method for BQRBSRCE by needling at Tanzhong
      (RN17), Zhongwan (RN12), Qihai (RN6), and bilateral Xuehai (SP10), and bilateral
      Zusanli (ST36).Two fixed non-acupoints from bilateral ribs were needled in the
      non-acupoint group. The p53 protein expression in the cortex and hippocampus of
      mice was determined using Western blot. The pathological changes of neurons in
      the hippocampal CA1 region, the temporal lobe, and the occipital lobe were
      observed using HE staining. The expression of cortical p53-positive cells was
      detected by immunohistochemical assay. RESULTS: The p53 protein was highly
      expressed in the cortex of SAMP8, which was significantly down-regulated after
      acupuncture, showing statistical difference when compared with the SAMP8 control
      group (P < 0.05), but with no statistical difference when compared with the SAMR1
      control group (P > 0.05). Needling at non-acupoints had no obvious effect on the
      p53 protein expression. There was no statistical difference in the p53 protein
      expression of the hippocampus (P > 0.05). CONCLUSION: Acupuncture method for
      BQRBSRCE could down-regulate the p53 protein expression in the brain of mice,
      improve the pathological state of brain cells, thus enhancing learning and memory
      capabilities of AD mice, improving their cognitive functions, with specificity of
      acupoints.

PMID- 24432682
TI  - [Effect of electroacupuncture on phosphorylation of NR2B at Tyr 1742 site in the
      spinal dorsal horn of CFA rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on phosphorylation of
      spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced
      inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly
      divided into normal group (N group, n = 10), the model group (CFA group, n = 15),
      and the EA group (n = 15). The inflammatory pain model was established by
      subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw
      withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as
      well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation
      of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day
      post-injection were detected using immunohistochemical assay. RESULTS: PWTs in
      the CFA group were significantly lower than those of the N group at every
      detective time point post-injection (P < 0.01). PWTs were obviously lower in the
      EA group than in the N group at 24 h post-injection (P < 0.01). It showed
      increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd
      day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B
      positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was
      up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in
      the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA
      group. CONCLUSION: EA might effectively inhibit CFA-induced inflammatory pain
      possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site
      in the ispilateral spinal dorsal horn.

PMID- 24432683
TI  - [Effect of modified sijunzi decoction on the bone metabolism of adriamycin
      induced nephropathy rats].
AB  - OBJECTIVE: To explore the effect of Modified Sijunzi Decoction (MSD) on the bone
      metabolism of prednisone intervened adriamycin-induced nephropathy rats. METHODS:
      The adriamycin-induced nephropathy rat model was prepared. Totally 50 SD rats
      were randomly divide into five groups, i.e., the model group, the hormone group,
      the Chinese medicine (CM) group, the CM + hormone group, and the normal control
      group. The 24-h urine samples were collected on the 7th, 21st, and 35th day after
      modeling. The 24-h urine protein was measured by biuret colorimetry. Serum levels
      of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand
      (RANKL), osteocalcin (BGP), and tartrate-resistant acid phosphatase (TRACP) were
      determined by ELISA. Expressions of OPG and RANKL in the tibia tissue were
      detected using real-time quantitative PCR and Western blot. RESULTS: (1) Compared
      with the normal control group, the 24-h urine protein increased in each group on
      the 7th, 21st, and 35th day (P < 0.05, P < 0.01). Compared with the model group,
      the 24-h urinary protein decreased in the hormone group and the CM + hormone
      group (P < 0.05, P < 0.01). The decrement was more obvious along with the
      treatment time went by (P < 0.05, P < 0.01). There was statistical difference in
      the reduction of urine protein on the 35th day between the CM group and the model
      group (P < 0.05). (2) Compared with the 21st-day of the same group, the serum
      levels of TRACP and RANKL increased (P < 0.05, P < 0.01). Compared with the model
      group, the serum levels of the TRACP and RANKL increased (P < 0.05, P < 0.01),
      OPG and BGP decreased (P < 0.05, P < 0.01) in the hormone group. Compared with
      the CM group at the same period, serum OPG level decreased and the RANKL level
      increased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01).
      Besides, the serum level of TRACP increased and BGP decreased (P < 0.05, P <
      0.01). Compared with the hormone group at the same period, OPG and BGP increased
      (P < 0.05, P < 0.01), RANKL decreased (P < 0.01) in the CM + hormone group. On
      the 35th day TRACP decreased (P < 0.01). (3) Compared with the normal group, mRNA
      expressions of OPG and RANKL on the 21st day increased (P < 0.05, P < 0.01), mRNA
      expressions of OPG and RANKL on the 35th day decreased in the model group (P <
      0.01). Compared with the CM group at the same period, OPG mRNA expression
      decreased (P < 0.01) and RANKL mRNA expression increased in the hormone group (P
      < 0.05). OPG mRNA expression decreased in the CM +hormone group (P < 0.05). (4)
      Compared with the hormone group on the 21st day, the OPG level decreased and the
      RANKL protein increased (both P < 0.05). RANKL decreased in the CM + hormone
      group (P < 0.05). Compared with the model group at the same period, OPG decreased
      and RANKL increased in the hormone group (P < 0.01). Compared with the CM group
      at the same period, OPG decreased (P < 0.01), RANKL increased (P < 0.01) in the
      hormone group and the CM + hormone group. Compared with the hormone group at the
      same period, OPG increased and RANKL decreased in the CM + hormone group (both P
      < 0.01). CONCLUSIONS: Prednisone could induce osteoporosis through the
      OPG/RANKL/RANK pathway. MSZ could slow down the formation of prednisone-induced
      osteoporosis through promoting osteoblast differentiation, and inhibiting
      osteoclastogenesis.

PMID- 24432684
TI  - [Effect of parthenolide on serum expressions of interleukin-1beta and tumor
      necrosis factor-alpha in rabbits with knee osteoarthritis].
AB  - OBJECTIVE: To observe the therapeutic effect of parthenolide (PTL) on rabbit knee
      arthritis (KOA) and its effects on serum expression of interleukin-1beta (IL
      1beta) and contents of tumor necrosis factor-alpha (TNF-alpha). METHODS: Eight
      rabbits were randomly selected from 40 healthy pure-bred New Zealand rabbits as
      the normal control group. The KOA model was established in the rest 32 rabbits by
      plaster cast fixation of the right hind limb extension position. After modeling
      they were randomly divided into 4 groups, i.e., the model control group, the high
      dose PTL group, the middle dose PTL group, and the low dose PTL group, 8 in each
      group. Serum contents of IL-1beta and TNF-alpha were detected using enzyme-linked
      immunosorbent assay. RESULTS: Compared with the model group, IL-1beta and TNF
      alpha concentration decreased in the 3 PTL groups (P < 0.01). The decrement was
      positively correlated with PTL concentrations (IL-1beta: r = 0.55, P < 0.01; TNF
      alpha: r = 0.56, P < 0.01). The inhibition reached the peak when the PTL
      concentration arrived at 20 micromol/L. CONCLUSIONS: PTL could down-regulate the
      blood IL-1beta and TNF-alpha concentrations of KOA rabbits. Besides, the
      decrement was positively correlated with the PTL concentration.

PMID- 24432685
TI  - [Effect of sanshui baihu decoction on the proliferation of fibroblast-like
      synoviocytes and its secretion of IL-6 and IL-17].
AB  - OBJECTIVE: To observe the effect of Sanshui Baihu Decoction (SBD) containing
      serum on the proliferation of in vitro cultured fibroblast-like synoviocytes
      (FLS) derived from rheumatoid arthritis (RA) and osteoarthritis (OA) and its
      secretion of interleukin-6 (IL-6) and IL-17, and to explore the pharmacological
      mechanism of SBD. METHODS: The FLS obtained from cultured RA and OA patients'
      synovial tissue were cultured and passaged in vitro in a routine way. The
      cultured medium was changed to DMEM with 20% SBD containing serum and cultured
      for 72 h after cultured for 3 to 6 generations. The proliferation rate of FLS was
      detected by MTT assay. Levels of IL-6 and IL-17 in the supernatant were detected
      by ELISA. Leflunomide and saline containing serum were used as positive and
      negative control respectively. RESULTS: SBD containing serum significantly
      inhibited the proliferation of RA-FLS and OA-FLS, and decreased the secretion of
      IL-17 in RA-FLS. Its inhibition efficiency of SBD was equivalent to that of
      Leflunomide. No obvious inhibition on the secretion of IL-6 in RA-FLS was
      observed. It had no significant effect on the secretion of IL-17 and IL-6 in OA
      FLS. CONCLUSION: SBD could inhibit the proliferation of FLS and the secretion of
      IL-17 in RA-FLS, which might be one of its pharmacological mechanisms for
      treating RA.

PMID- 24432686
TI  - [Effect of sijunzi decoction on the intestinal glucose absorption in model rats
      of Pi-qi deficiency syndrome: an experimental research].
AB  - OBJECTIVE: To observe the effect of Sijunzi Decoction (SD) on the intestinal
      absorption of glucose in model rats of Pi-qi deficiency syndrome (PQDS). METHODS:
      PQDS rat model was established by subcutaneous injection of reserpine from the
      neck. The body weight and urine D-xylose excretion rates were measured. The
      glucose uptake rate was measured by jejunum perfusion. The intestinal mucosa was
      collected. The glucose transporter-2 (GLUT2) protein and mRNA expression levels
      were detected. RESULTS: Compared with the normal control group, the body weight
      and D-xylose excretion rates decreased in the model group. Meanwhile, the glucose
      uptake and GLUT2 protein and mRNA expression levels decreased in the model group.
      The aforesaid indices were improved in the SD group. CONCLUSION: SD could promote
      the recovery of glucose uptake in the small intestine of reserpine induced PQDS
      rats.

PMID- 24432687
TI  - [Effect of Trigonella foenum-graecum 4-hydroxyisoleucine on high-glucose induced
      insulin resistance in 3T3-L1 adipocytes of mice].
AB  - OBJECTIVE: To investigate the effect of 4-hydroxyisoleucine (4-HIL), an active
      component of Trigonella Foenum-graecum L. on high glucose induced insulin
      resistance (IR) in 3T3-L1 adipocytes, and to explore underlying molecular
      mechanisms. METHODS: 3T3-L1 adipocytes were treated with 25 mmol/L glucose and
      0.6 nmol/L insulin to induce IR. They were intervened by different concentrations
      of 4-HIL (at 5, 10, and 20 micromol/L). [3H]-Deoxy-D-glucose up-taking method was
      used to detect the glucose uptake. The mRNA expression of cellular tumor necrosis
      factor-alpha (TNF-alpha) was detected by polymerase chain reaction (PCR). The
      content of TNF-alpha in the culture supernatant was detected by enzyme-linked
      immunosorbent assay (ELISA). Palmitic acid (PA) acted as the control. RESULTS:
      After intervened by 25 mmol/L glucose and 0.6 nmol/L insulin for 18 h, the
      insulin-stimulated glucose transportation in 3T3-L1 adipocytes was inhibited by
      63%. The mRNA expression of cellular TNF-alpha in adipocytes significantly
      increased, when compared with that in normal adipocytes (P < 0.05). The level of
      TNF-alpha secreted in the culture supernatant was increased by 70 pg/mL (P <
      0.05). Similar changes occurred in the PA group. After exposure to 4-HIL (5, 10,
      or 20 micromol/L) for 24 h, the glucose transportation was increased by 35%, 50%,
      and 60%, respectively. PCR results showed that along with increasing 4-HIL
      concentrations, the mRNA expression of cellular TNF-alpha showed a decreasing
      trend, showing statistical difference when compared with the model group and the
      PA group (P < 0.05). Compared with the model group, the TNF-alpha level in the
      supernatant was respectively reduced by 10 pg/mL, 18 pg/mL, and 39 pg/mL after
      intervention (P < 0.05). CONCLUSION: 4-HIL could remarkably improve high glucose
      induced IR in 3T3-L1 adipocytes. Meanwhile, 4-HIL could inhibit the secretion of
      TNF-alpha.

PMID- 24432688
TI  - [Effect of Chinese herbal compounds for blood activating stasis removing, qi
      benefiting Shen invigorating on high glucose stimulated proliferation of renal
      mesangial cells and expressions of fibronectin].
AB  - OBJECTIVE: To study effects of Chinese Herbal Compounds (CHC) for blood
      activating stasis removing (BASR), qi benefiting Shen invigorating (QBSI) on high
      glucose stimulated proliferation of renal mesangial cells (RMCs) and expressions
      of fibronectin (FN). METHODS: Rats' RMCs were dealt with high glucose and
      different concentrations of Chinese medicine for 24 and 48 h respectively. The
      proliferation of RMCs was detected with 4-A thiazolyl blue. mRNA expressions of
      FN was detected by real time quantitative PCR. The protein expression of FN was
      detected by ELISA. RESULTS: Compared with the control group, the proliferation
      obviously increased (P < 0.05, P < 0.01) after 24 and 48 h of treatment in the
      high glucose group, mRNA and protein expressions of FN also increased (P < 0.01).
      There was no statistical difference in the proliferation of RMCs or expressions
      of FN at 24 h between each CHC group and the high glucose group (P > 0.05).
      Compared with the high glucose group, the proliferation of RMCs and expressions
      of FN at 24 h each obviously decreased in the CHC group (P < 0.05, P < 0.01).
      CONCLUSIONS: High glucose could promote the proliferation of RMCs and induce
      expressions of FN. No obvious effect could be stimulated by CHC treatment for 24
      h. The proliferation of RMCs, protein and mRNA expressions of FN could be
      reversed by CHC treatment for 48 h.

PMID- 24432689
TI  - [Effect of Lycium barbarum polysaccharides on the retinal ultrastructure of
      streptozocin-induced diabetic rats].
AB  - OBJECTIVE: To study the retinal ultrastructure of streptozocin (STZ)-induced
      diabetic rats and the intervention effect of Lycium Barbarum Polysaccharides
      (LBP). METHODS: The STZ-induced diabetic SD rat model was established. LBP was
      given to those in the treatment group by gastrogavage. Changes of body weight,
      blood glucose, and retinal ultrastructure at 24-week were observed. RESULTS:
      Early retinal changes covered mitochondrion changes, cell degeneration and
      apoptosis of retinal neurons and neuroglia cells in the diabetic rats. No change
      of body weight or blood glucose was observed between the LBP group and the
      diabetic model group (P > 0.05). The ultrastructural changes were obviously
      relieved by LBP, and limited to the inner nuclear layer. CONCLUSIONS: LBP could
      obviously relieve pathological changes of mitochondrion, hinder neural cell
      apoptosis. Its effect might not be achieved by lowering blood glucose. It was
      expected to be used in preventing and treating early diabetic retinal neuropathy.

PMID- 24432690
TI  - [Effect of reinforcing qi for resolving masses method on expressions of MEK2 and
      p-ERK protein in estrogen induced uterine leiomyoma model guinea pigs' uterine
      tissue].
AB  - OBJECTIVE: To explore the effect of reinforcing qi for resolving masses method
      (RQRMM) on expressions of extracellular signal regulated kinase 2 (MEK2) and
      phosphorylation extracellular signal regulated kinase (p-ERK) protein in estrogen
      induced uterine leiomyoma model Guinea pigs' uterine tissue. METHODS: Guinea pigs
      were randomly divided into five groups, i.e., the model group, the high dose
      group, the middle dose group, the low dose group, and the Western medicine group
      (mifepristone). The normal control group was set up. The uterine leiomyoma model
      in guinea pigs was established by castrating and subcutaneous injecting estradiol
      (E2). The protein expression levels of MEK2 and p-ERK of guinea pigs' uterine
      tissues were detected by immunohistochemical assay. RESULTS: The protein
      expressions of MEK2 and p-ERK in the uterine muscular tissue of Guinea pigs'
      uterine tissue were higher in the model group than in the normal group (P <
      0.01). They decreased to some degree in the high dose group, the middle dose
      group, and the low dose group. Of them, the protein expressions of MEK2 and p-ERK
      were significantly lower in the high dose group than in the model group and the
      Western medicine group (P < 0.01). CONCLUSION: RQRMM could treat uterine
      leiomyoma possibly through intervening the MAPK/ERK cell signal pathway to
      inhibit the proliferation of myoma cells.

PMID- 24432691
TI  - [Modern elucidative strategies for scientific connotation of controlling toxic
      reactions while toxic herbs are used to the indication syndrome].
AB  - One of effective measures for controlling toxic reactions is to use toxic herbs
      according to corresponding indication syndrome. It is important to develop
      toxicity theory of Chinese medicine in a sound and international way using modern
      language to elucidate its scientific connotation. We expect to explain scientific
      connotation of controlling toxic reaction while toxic herbs are used to the
      indication syndrome by using holistic research ideas and methods capable of
      reflecting governing exterior to infer interior, establish appropriate
      corresponding syndrome animal models by cutting into dose-effect/toxicity of
      toxic Chinese herbs, construct and analyze multi-layer molecular network using
      theories and technologies of metabonomics, network biology, and bioinformatics.

PMID- 24432692
TI  - [Regulatory roles of compound danshen in the downstream path of cyclooxygenases
      in rheumatoid arthritis patients' synovium].
AB  - Rheumatoid arthritis (RA) belongs to Bi syndrome (arthralgia) in Chinese
      medicine. Till now there lacks effective therapeutic methods. Recently
      cyclooxygenases (COXs) inhibitors, having regulator roles for many pro
      inflammatory cytokines, have been widely used in RA treatment. But due to
      existing cardiovascular risks, researches on targeting the downstream specific
      factors of COXs have been under discussion. Considering the key role of blood
      stasis syndrome (BSS) in the pathology of RA and the fact that thromboxane A2
      (TXA2) plays a pivotal role in BSS, we theoretically explored possible regulatory
      roles of Compound Danshen, a representative therapy in blood activating stasis
      removing method in the downstream path of COXs in synovial cells of RA. We
      proposed a brand new research direction of RA researches.

PMID- 24432693
TI  - [Thinking on the direction of education of integrative medicine].

PMID- 24432694
TI  - [Research progress of treating spinal cord injuries by Chinese medicine].

PMID- 24432695
TI  - [Research progress of intervening cerebral infarction by Chinese herbal
      injection].

PMID- 24432696
TI  - [Experimental research progress of treating viral myocarditis by Chinese
      medicine].

PMID- 24432697
TI  - Vapor-liquid-solid growth of one-dimensional tin sulfide (SnS) nanostructures
      with promising field emission behavior.
AB  - Single-crystalline ultralong tin sulfide (SnS) nanowires has been grown by a
      thermal evaporation technique under optimized conditions on gold-coated silicon
      substrates, and for the first time, field emission investigations on the SnS
      nanowires at the base pressure of 1 * 10(-8) mbar are reported. It has been
      revealed that the surface morphology of the as-synthesized SnS nanostructures is
      significantly influenced by the deposition temperature and duration. Structural
      and morphological analyses of as-synthesized SnS nanostructures have been carried
      out using X-ray diffraction (XRD), scanning electron microscopy (SEM), and
      transmission electron microscopy (TEM). To understand the optical and electronic
      properties of as-synthesized SnS nanowires, ultraviolet-visible (UV-vis),
      photoluminescence (PL), and X-ray photoelectron spectroscopy (XPS) studies were
      carried out. The SEM and TEM measurements reveal the formation of ultralong SnS
      nanowires, with an average diameter of 80 nm. A plausible explanation on the
      vapor-solid-liquid (VLS) growth mechanism based on the experimental results and
      reported literature has been presented. Furthermore, the field emission
      characteristics of the SnS nanowires are found to be superior to the other metal
      chalcogenide nanostructures. The synthesized SnS nanowire emitter delivers a high
      current density of ~2.5 mA/cm(2) at an applied electric field of ~4.55 V/MUm. The
      emission current stability over a period of 6 h is observed to be good. The
      observed results demonstrate the potential of the SnS nanowire emitter as an
      electron source for practical applications in vacuum nano/microelectronic
      devices. 

PMID- 24432698
TI  - Engineered lysozyme amyloid fibril networks support cellular growth and
      spreading.
AB  - Fibrous networks assembled from synthetic peptides are promising candidates for
      biomimetic cell culture platforms and implantable biomaterials. The ability of
      the materials to reproduce physiological cell-matrix interactions is essential.
      However, the synthetic complexity of such systems limits their applications, thus
      alternative materials are desirable. Here, we design lysozyme derived amyloid
      fibril networks with controllable topographies, and perform a comprehensive study
      of the response of cultured fibroblast and epithelial cells. At high surface
      coverage a favorable increase in spreading and the generation of focal adhesions
      was observed, due to a combination of biomimetic chemistry and morphology. Their
      ease of synthesis, makes the nanoscale fibrils presented here ideal materials for
      future clinical applications whereby large volumes of biomimetic biomaterials are
      required. Furthermore, the surface chemistry of the fibrils is sufficient for the
      promotion of focal adhesions with cultured cells, eliminating the need for
      complex protocols for fibril decoration with bioactive moieties. 

PMID- 24432703
TI  - Characterization of fruit products by capillary zone electrophoresis and liquid
      chromatography using the compositional profiles of polyphenols: application to
      authentication of natural extracts.
AB  - Capillary zone electrophoresis (CZE) and high performance liquid chromatography
      (HPLC) were applied to the authentication of fruit products based on the
      compositional profiles of polyphenols. Various sample treatments were used to
      maximize the overall recovery of polyphenols or specific fractions, such as
      phenolic acids or anthocyanins. The resulting CZE and HPLC data were treated with
      Principal Component Analysis (PCA) showing that samples were mainly clustered
      according to the fruit of origin, with cranberry- and grape-based products
      clearly separated in groups. A possible adulterated cranberry extract was
      analyzed more deeply by high resolution mass spectrometry (HRMS) in order to
      identify the presence of A-type proanthocyanidins, which are characteristic and
      more abundant in cranberry-based products. In accordance with PCA interpretation,
      HRMS results indicated that the suspicious sample was not a cranberry-based
      product, allowing us to validate and demonstrate the suitability of both CZE- and
      HPLC-proposed methods for the characterization of fruit-based products. 

PMID- 24432702
TI  - Highly emitting near-infrared lanthanide "encapsulated sandwich" metallacrown
      complexes with excitation shifted toward lower energy.
AB  - Near-infrared (NIR) luminescent lanthanide complexes hold great promise for
      practical applications, as their optical properties have several complementary
      advantages over organic fluorophores and semiconductor nanoparticles. The
      fundamental challenge for lanthanide luminescence is their sensitization through
      suitable chromophores. The use of the metallacrown (MC) motif is an innovative
      strategy to arrange several organic sensitizers at a well-controlled distance
      from a lanthanide cation. Herein we report a series of lanthanide "encapsulated
      sandwich" MC complexes of the form Ln3+ [12-MC(Zn(II),quinHA)-4]2[24
      MC(Zn(II),quinHA)-8] (Ln3+ [Zn(II)MC(quinHA)]) in which the MC framework is
      formed by the self-assembly of Zn2+ ions and tetradentate chromophoric ligands
      based on quinaldichydroxamic acid (quinHA). A first-generation of luminescent MCs
      was presented previously but was limited due to excitation wavelengths in the UV.
      We report here that through the design of the chromophore of the MC assembly, we
      have significantly shifted the absorption wavelength toward lower energy (450
      nm). In addition to this near-visible inter- and/or intraligand charge transfer
      absorption, Ln3+ [Zn(II)MC(quinHA)] exhibits remarkably high quantum yields, long
      luminescence lifetimes (CD3OD; Yb3+, QLn(L) = 2.88(2)%, tauobs = 150.7(2) MUs;
      Nd3+, QLn(L) = 1.35(1)%, tauobs = 4.11(3) MUs; Er3+, QLn(L) = 3.60(6).10-2%,
      tauobs = 11.40(3) MUs), and excellent photostability. Quantum yields of Nd3+ and
      Er3+ MCs in the solid state and in deuterated solvents, upon excitation at low
      energy, are the highest values among NIR-emitting lanthanide complexes containing
      C-H bonds. The versatility of the MC strategy allows modifications in the
      excitation wavelength and absorptivity through the appropriate design of the
      ligand sensitizer, providing a highly efficient platform with tunable properties.

PMID- 24432704
TI  - Isothiourea-catalyzed asymmetric synthesis of beta-lactams and beta-amino esters
      from arylacetic acid derivatives and N-sulfonylaldimines.
AB  - The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2]
      cycloaddition of both arylacetic acids (following activation with tosyl chloride)
      and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating
      stereodefined 2,3-diaryl-beta-amino esters (after ring-opening) and 3,4-diaryl
      anti-beta-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and
      good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within
      the beta-lactam framework was possible without racemization by treatment with
      SmI2. 

PMID- 24432705
TI  - Urology and nephrology update: foreword.

PMID- 24432706
TI  - Urology and nephrology update: proteinuria and hematuria.
AB  - Proteinuria and hematuria can be benign or can be signs of more serious
      underlying pathology. The diagnostic evaluation should take into account the age
      of the patient as well as medical history, family history, concurrent symptoms,
      initial physical examination findings, and basic office laboratory test results.
      There are many tests to consider for proteinuria and hematuria. Routine screening
      for proteinuria is not recommended in the general population, but it is
      recommended for high-risk patients, such as those with diabetes and hypertension.
      Asymptomatic patients should not be screened for hematuria. Patients should be
      referred to a nephrology subspecialist if proteinuria is drug-resistant, if there
      is persistent hematuria with concomitant proteinuria, or if a renal biopsy is
      being considered. Patients should be referred to a urology subspecialist for
      abnormal genitourinary anatomy, trauma, stones, tumors, nonglomerular gross
      hematuria, or persistent microscopic hematuria. 

PMID- 24432707
TI  - Urology and nephrology update: anemia of chronic kidney disease.
AB  - Anemia is associated with chronic kidney disease (CKD) at all stages, and it is
      nearly universal among patients with stage 5 CKD. Nonetheless, anemia of CKD is a
      diagnosis of exclusion. When anemia is detected in a patient with CKD, etiologies
      other than CKD must be considered and ruled out. Iron deficiency also is common
      among patients with CKD, and iron replenishment improves the anemia and the
      response to erythropoiesis-stimulating agents. Current guidelines for managing
      anemia of CKD recommend a hemoglobin goal of 11 to 12 g/dL, but lower hemoglobin
      may be acceptable for asymptomatic patients. Some patients do not benefit from
      erythropoiesis-stimulating agents, or they lose their responsiveness to treatment
      and transfusions must be considered. Other agents are being investigated as
      management for anemia of CKD, with vitamin C (ascorbic acid) showing some
      promise.

PMID- 24432708
TI  - Urology and nephrology update: bladder and kidney cancer.
AB  - It has been estimated that bladder and kidney cancers would be diagnosed in
      approximately 140,000 Americans in 2013, with approximately 30,000 dying from
      these cancers. Urinary tract cancers affect men more commonly than they do women,
      and the median age at diagnosis is 65 years. Major risk factors for these cancers
      include tobacco smoking, certain chemical exposures, family history, age, and
      obesity. Unexplained hematuria in adults should be evaluated to exclude bladder
      and kidney cancer. Staging of bladder and kidney cancer should be based on the
      TNM staging system, which, along with tumor grade, provides important treatment
      and prognostic information. Urothelial cell carcinoma is the most common type of
      bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma
      is the most common type of kidney cancer. Treatment options for bladder cancer
      vary widely, depending on the grade of the cancer. Early non-muscle-invasive
      bladder cancer may be removed cystoscopically and/or treated with intravesical
      immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder
      tumors typically require surgery. Management of kidney cancer is almost always
      surgical, unless the patient is too ill to undergo surgery or chooses palliative
      care. 

PMID- 24432709
TI  - Urology and nephrology update: recurrent urinary tract infection.
AB  - Urinary tract infections (UTIs) are common among children and adults, with the
      greatest prevalence in women. One-half of all women will develop a UTI at some
      point. Approximately one-third of children with UTIs develop recurrent
      infections, and because recurrent UTIs have been thought to lead to renal
      scarring, practice has focused on identifying patients at risk of UTIs and
      limiting recurrence. It is difficult to determine which children are at risk of
      renal damage, and the benefits of antibiotics or surgery in preventing recurrent
      UTIs in children are unclear. Therefore, recent guidelines have taken a less
      aggressive approach to the prevention of recurrent UTIs in children. Recurrent
      UTIs also may be an issue for women. Sexual intercourse is a major risk factor,
      and postcoital prophylactic antibiotic treatment has been shown to be effective.
      Immediate antibiotic treatment of UTI symptoms also has shown efficacy. Although
      cranberry supplements or juice may be effective, the benefit of other commonly
      recommended treatments, such as frequent or postcoital voiding, increased fluid
      consumption, and avoiding bubble baths, has not been shown. 

PMID- 24432710
TI  - Optimizing vanadium pentoxide thin films and multilayers from dip-coated
      nanofluid precursors.
AB  - Using an alkoxide-based precursor, a strategy for producing highly uniform thin
      films and multilayers of V2O5 is demonstrated using dip coating. Defect-free and
      smooth films of V2O5 on different surfaces can be deposited from liquid
      precursors. We show how pinholes are formed due to heterogeneous nucleation
      during hydrolysis as the precursor forms a nanofluid. Using knowledge of
      instability formation often found in composite nanofluid films and the influence
      of cluster formation on the stability of these films, we show how polymer
      precursor mixtures provide optimum uniformity and very low surface roughness in
      amorphous V2O5 and also orthorhombic V2O5 after crystallization by heating.
      Pinhole and roughness instability formation during the liquid stage of the
      nanofluid on gold and ITO substrates is suppressed giving a uniform coating.
      Practically, understanding evolution pathways that involve dewetting processes,
      nucleation, decomposition, or hydrolysis in complex nanofluids provides a route
      for improved uniformity of thin films. The method could be extended to improve
      the consistency in sequential or iterative multilayer deposits of a range of
      liquid precursors for functional materials and coatings. 

PMID- 24432711
TI  - Continuous flow alpha-trifluoromethylation of ketones by metal-free visible light
      photoredox catalysis.
AB  - A continuous-flow, two-step procedure for the preparation of alpha-CF3
      substituted carbonyl compounds has been developed. The carbonyl substrates were
      converted in situ into the corresponding silyl enol ethers, mixed with the CF3
      radical source, and then irradiated with visible light using a flow reactor based
      on transparent tubing and a household compact fluorescent lamp. The continuous
      protocol uses Eosin Y as an inexpensive photoredox catalyst and requires only 20
      min to complete the two reaction steps. 

PMID- 24432712
TI  - Performance of the EXAcerbations of chronic pulmonary disease tool patient
      reported outcome measure in three clinical trials of chronic obstructive
      pulmonary disease.
AB  - RATIONALE: The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) is a
      patient-reported outcome measure to standardize the symptomatic assessment of
      chronic obstructive pulmonary disease exacerbations, including reported and
      unreported events. The instrument has been validated in a short-term study of
      patients with acute exacerbation and stable disease; its performance in longer
      term studies has not been assessed. OBJECTIVES: To test the EXACT's performance
      in three randomized controlled trials and describe the relationship between
      resource-defined medically treated exacerbations (MTEs) and symptom (EXACT)
      defined events. METHODS: Prespecified secondary analyses of data from phase II
      randomized controlled trials testing new drugs for the management of chronic
      obstructive pulmonary disease: one 6-month trial (United States) (n = 235) and
      two 3-month, multinational trials (AZ 1 [n = 749], AZ 2 [n = 597]). In each case,
      the experimental drugs were found to be ineffective, permitting assessment of the
      EXACT's performance in three independent studies of moderate to severe high-risk
      patients on maintenance therapies. MEASUREMENTS AND MAIN RESULTS: The mean age of
      subjects was 62 to 64 years; 48 to 76% were male. Mean FEV1 % predicted was 42 to
      59%. EXACT scores exhibited internal consistency (Cronbach's alpha >= 0.90),
      reproducibility (intraclass correlation >= 0.70), correlation with St. George's
      Respiratory Questionnaire (Spearman rho [rs] = 0.62, 0.46, 0.46 in the three
      trials; P < 0.001), and Breathlessness Cough and Sputum Scale (AZ 1, rs = 0.83;
      AZ 2, rs = 0.83; P < 0.001). EXACT-defined events had a high correspondence with
      alternative indicators of worsening (94, 88, and 93%). In each trial, unreported
      events were similar in severity (mean EXACT score, 56, 57, 61 vs. 53, 54 [P <
      0.05], 57 [P < 0.05], respectively; 100-point scale) and longer (median, 9, 8, 7
      vs. 8, 7 [P < 0.01], 6 days, respectively) than moderate MTEs. CONCLUSIONS: Data
      generated through the EXACT offers insight into the symptomatic nature of MTEs
      and the frequency, severity, and duration of unreported symptom-defined events.
      Clinical trials registered with www.clinicaltrials.gov (MPEX: NCT00739648; AZ 1:
      NCT00949975; AZ 2: NCT01023516).

PMID- 24432713
TI  - Light-responsive micelles of spiropyran initiated hyperbranched polyglycerol for
      smart drug delivery.
AB  - Light-responsive polymeric micelles have emerged as site-specific and time
      controlled systems for advanced drug delivery. Spiropyran (SP), a well-known
      photochromic molecule, was used to initiate the ring-opening multibranching
      polymerization of glycidol to afford a series of hyperbranched polyglycerols (SP
      hb-PG). The micelle assembly and disassembly were induced by an external light
      source owing to the reversible photoisomerization of hydrophobic SP to
      hydrophilic merocyanine (MC). Transmission electron microscopy, atomic force
      microscopy, UV/vis spectroscopy, and dynamic light scattering demonstrated the
      successful assembly and disassembly of SP-hb-PG micelles. In addition, the
      critical micelle concentration (CMC) was determined through the fluorescence
      analysis of pyrene to confirm the amphiphilicity of respective SP-hb-PGn (n = 15,
      29, and 36) micelles, with CMC values ranging from 13 to 20 mg/L, which is
      correlated to the length of the polar polyglycerol backbone. Moreover, the
      superior biocompatibility of the prepared SP-hb-PG was evaluated using WI-38
      cells and HeLa cells, suggesting the prospective applicability of the micelles in
      smart drug delivery systems. 

PMID- 24432714
TI  - Synthesis, spectral characterization, structures, and oxidation state
      distributions in [(corrolato)Fe(III)(NO)](n) (n = 0, +1, -1) complexes.
AB  - Two novel trans-A2B-corroles and three [(corrolato){FeNO}(6)] complexes have been
      prepared and characterized by various spectroscopic techniques. In the native
      state, all these [(corrolato){FeNO}(6)] species are diamagnetic and display
      "normal" chemical shifts in the (1)H NMR spectra. For two of the structurally
      characterized [(corrolato){FeNO}(6)] derivatives, the Fe-N-O bond angles are
      175.0(4) degrees  and 171.70(3) degrees  (DFT: 179.94 degrees ), respectively,
      and are designated as linear nitrosyls. The Fe-N (NO) bond distances are 1.656(4)
      A and 1.650(3) A (DFT: 1.597 A), which point toward a significant Fe(III) -> NO
      back bonding. The NO bond lengths are 1.159(5) A and 1.162(3) A (DFT: 1.162 A)
      and depict their elongated character. These structural data are typical for low
      spin Fe(III). Electrochemical measurements show the presence of a one-electron
      oxidation and a one-electron reduction process for all the complexes. The one
      electron oxidized species of a representative [(corrolato){FeNO}(6)] complex
      exhibits ligand to ligand charge transfer (LLCT) transitions (cor(pi) ->
      cor(pi*)) at 399 and 637 nm, and the one-electron reduced species shows metal to
      ligand charge transfer (MLCT) transition (Fe(dpi) -> cor(pi*)) in the UV region
      at 330 nm. The shift of the nuNO stretching frequency of a representative
      [(corrolato){FeNO}(6)] complex on one-electron oxidation occurs from 1782 cm(-1)
      to 1820 cm(-1), which corresponds to 38 cm(-1), and on one-electron reduction
      occurs from 1782 cm(-1) to 1605 cm(-1), which corresponds to 177 cm(-1). The X
      band electron paramagnetic resonance (EPR) spectrum of one-electron oxidation at
      295 K in CH2Cl2/0.1 M Bu4NPF6 displays an isotropic signal centered at g = 2.005
      with a peak-to-peak separation of about 15 G. The in situ generated one-electron
      reduced species in CH2Cl2/0.1 M Bu4NPF6 at 295 K shows an isotropic signal
      centered at g = 2.029. The 99% contribution of corrole to the HOMO of native
      species indicates that oxidation occurs from the corrole moiety. The results of
      the electrochemical and spectroelectrochemical measurements and density
      functional theory calculations clearly display a preference of the {FeNO}(6) unit
      to get reduced during the reduction step and the corrolato unit to get oxidized
      during the anodic process. Comparisons are presented with the structural,
      electrochemical, and spectroelectrochemical data of related compounds reported in
      the literature, with a particular focus on the interpretation of the EPR spectrum
      of the one-electron oxidized form. 

PMID- 24432717
TI  - Copper-catalyzed allylation of alpha,alpha-difluoro-substituted organozinc
      reagents.
AB  - A method for the coupling of organozinc reagents, difluorocarbene, and allylic
      electrophiles is described. The reaction involves insertion of difluorocarbene
      into the carbon-zinc bond followed by copper-catalyzed allylic substitution. 

PMID- 24432718
TI  - Large entropic effects on the thermochemistry of silicon nanodusty plasma
      constituents.
AB  - Determination of the thermodynamic properties of reactor constituents is the
      first step in designing control strategies for plasma-mediated deposition
      processes and is also a key fundamental issue in physical chemistry. In this
      work, a recently proposed multistructural statistical thermodynamic method is
      used to show the importance of multiple structures and torsional anharmonicity in
      determining the thermodynamic properties of silicon hydride clusters, which are
      important both in plasmas and in thermally driven systems. It includes five
      different categories of silicon hydride clusters and radicals, including silanes,
      silyl radicals, and silenes. We employed a statistical mechanical approach,
      namely the recently developed multistructural (MS) anharmonicity method, in
      combination with density functional theory to calculate the partition functions,
      which in turn are used to estimate thermodynamic quantities, namely Gibbs free
      energy, enthalpy, entropy, and heat capacity, for all of the systems considered.
      The calculations are performed using all of the conformational structures of each
      molecule or radical by employing the multistructural quasiharmonic approximation
      (MS-QH) and also by including torsional potential anharmonicity (MS-T). For those
      cases where group additivity (GA) results are available, the thermodynamic
      quantities obtained from our MS-T calculations differ considerably due to the
      fact that the GA method is based on single-structure data for isomers of each
      stoichiometry, and hence lack multistructural effects; whereas we find that
      multistructural effects are very important in silicon hydride systems. Our
      results also indicate that the entropic effect on the thermochemistry is huge and
      is dominated by multistructural effects. The entropic effect of multiple
      structures is also expected to be important for other kinds of chain molecules,
      and its effect on nucleation kinetics is expected to be large. 

PMID- 24432721
TI  - Thiabendazole uptake in shimeji, king oyster, and oyster mushrooms and its
      persistence in sterile and nonsterile substrates.
AB  - Thiabendazole in the substrates incurred from spraying and premixing was
      translocated to the pileus, stipe, and volva of selected mushrooms. The spraying
      on the substrates resulted in higher residues of thiabendazole in all three
      mushrooms than the premixing treatment. For premixing, in the five substrates,
      half-lives of thiabendazole were found to be 13.6 days for shimeji, 10.0 days for
      king oyster, 13.7 days for oyster, 19.1 days for sterilized substrate, and 8.4
      days for nonsterilized substrate, respectively. For spraying, the longest and
      shortest half-lives were found to be 19.5 and 8.1 days for the nonsterilized and
      sterilized substrates, respectively. The residues of thiabendazole in three
      edible fungi were increased with the incubation days from 3 to 5 to 7. The
      residues of thiabendazole in king oyster were the highest among the three fungi
      while those in shimeji and oyster showed similar patterns. 

PMID- 24432722
TI  - Highly enantioselective organocatalytic alpha-sulfenylation of azlactones.
AB  - The first asymmetric alpha-sulfenylation of azlactones with N
      (sulfanyl)succinimides has been developed by using cinchona alkaloid-derived
      squaramide as a catalyst and 4 A molecular sieves as an additive. The reaction
      conditions were suitable to 4-alkyl and benzyl-substituted azlactones as well as
      N-(benzyl/alkyl/arylthio)succinimides, affording adducts with high
      enantioselectivities (81-94% ee). 

PMID- 24432723
TI  - MMP-12 as a new marker of Stanford-A acute aortic dissection.
AB  - BACKGROUND: The study evaluated macrophage cytokines and macrophage
      metalloprotease (MMP)-12 levels in patients with Stanford-A acute aortic
      dissection (AAD) and in patients with critical carotid artery stenosis (CAS)
      compared with patients matched for age, sex, and traditional cardiovascular risk
      factors (RF). The aim was to identify possible early serum markers of risk for
      atherosclerotic complications. MATERIALS AND METHODS: We selected 65 patients: 23
      AAD patients, 21 CAS patients, 21 RF, and 10 healthy subjects (HS). In each
      patient and control serum, levels of interleukin (IL)-6, IL-8, tumour necrosis
      factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, vascular
      endothelial growth factor (VEGF), and MMP-12 were assessed by ELISA. RESULTS: A
      significant increase of MMP-12, IL-6, and IL-8 levels in AAD versus CAS was
      found. Moreover, MMP-12 was shown to be significantly higher in AAD versus RF,
      but not in CAS versus RF. A significant increase of IL-6, IL-8, MCP-1, TNF-alpha,
      and VEGF levels was observed both in AAD and CAS versus RF. CONCLUSIONS: The
      results suggest that MMP-12 may be considered to be a specific marker of Stanford
      A AAD. Furthermore, the study confirmed that in AAD and CAS macrophage cytokines
      play a key role in the progression of the atherosclerotic disease towards
      complications.

PMID- 24432724
TI  - Gold nanorod-embedded electrospun fibrous membrane as a photothermal therapy
      platform.
AB  - A strategy of using a gold nanorod (GNR)-loaded electrospun membrane as a
      photothermal therapy platform of cancer is reported. The strategy takes both the
      advantages of the excellent photothermal properties of GNRs to selectively kill
      the cancerous cells, and the widely used biodegradable electrospun membrane to
      serve as GNR-carrier and surgical recovery material. PEG modified GNRs were
      embedded into the electrospun fibrous membrane which was composed of PLGA and PLA
      b-PEG with an 85:15 ratio. After incubation with the cells in the cell culture
      medium, the PEG-GNRs were released from the membrane and taken up by cancer
      cells, allowing the generation of heat upon NIR irradiation to induce cancer cell
      death. We have demonstrated that the use of PEG-GNR-embedded membrane selectively
      killed the cancerous cells and effectively inhibited cancer cell proliferation
      though in vitro experiments. The PEG-GNRs-loaded membrane is a promising material
      for postsurgical recovery of cancer. 

PMID- 24432725
TI  - Tuning gelation time and morphology of injectable hydrogels using ketone
      hydrazide cross-linking.
AB  - Injectable, covalently in situ forming hydrogels based on poly(N
      isopropylacrylamide) have been designed on the basis of mixing hydrazide
      functionalized nucleophilic precursor polymers with electrophilic precursor
      polymers functionalized with a combination of ketone (slow reacting) and aldehyde
      (fast reacting) functional groups. By tuning the ratio of aldehyde:ketone
      functional groups as well as the total number of ketone groups in the
      electrophilic precursor polymer, largely independent control over hydrogel
      properties including gelation time (from seconds to hours), degradation kinetics
      (from hours to months), optical transmission (from 1 to 85%), and mechanics (over
      nearly 1 order of magnitude) can be achieved. In addition, ketone-functionalized
      precursor polymers exhibit improved cytocompatibility at even extremely high
      concentrations relative to polymers functionalized with aldehyde groups, even at
      4-fold higher functional group densities. Overall, increasing the ketone content
      of the precursor copolymers can result in in situ-gellable hydrogels with
      improved transparency and biocompatibility and equivalent mechanics and stimuli
      responsiveness while only modestly sacrificing the speed of gel formation. 

PMID- 24432726
TI  - Formation constants of copper(II) complexes with tripeptides containing Glu, Gly,
      and His: potentiometric measurements and modeling by generalized multiplicative
      analysis of variance.
AB  - We report a systematic study of the effects of types and positions of amino acid
      residues of tripeptides on the formation constants logbeta, acid dissociation
      constants pKa, and the copper coordination modes of the copper(II) complexes with
      27 tripeptides formed from the amino acids glutamic acid, glycine, and histidine.
      logbeta values were calculated from pH titrations with l mmol L(-1):1 mmol L(-1)
      solutions of the metal and ligand and previously reported ligand pKa values.
      Generalized multiplicative analysis of variance (GEMANOVA) was used to model the
      logbeta values of the saturated, most protonated, monoprotonated, logbeta(CuL) -
      logbeta(HL), and pKa of the amide group. The resulting model of the saturated
      copper species has a two-term model describing an interaction between the central
      and the C-terminal residues plus a smaller, main effect of the N-terminal
      residue. The model supports the conclusion that two copper coordination modes
      exist depending on the absence or presence of His at the central position, giving
      species in which copper is coordinated via two or three fused chelate rings,
      respectively. The GEMANOVA model for pKamide, which is the same as that for the
      saturated complex, showed that Gly-Gly-His has the lowest pKamide values among
      the 27 tripeptides. Visible spectroscopy indicated the formation of metal-ligand
      dimers for tripeptides His-His-Gly and His-His-Glu, but not for His-His-His, and
      the formation of multiple ligand bis compexes CuL2 and Cu(HL)2 for tripeptides
      (Glu/Gly)-His-(Glu/Gly) and His-(Glu/Gly)-(Glu/Gly), respectively. 

PMID- 24432733
TI  - Liquid crystal-based proton sensitive glucose biosensor.
AB  - A transmission electron microscopy (TEM) grid filled with 4-cyno-4-pentylbiphenyl
      (5CB) on the octadecyltrichloro silane-coated glass in an aqueous medium was
      developed to construct a glucose biosensor by coating poly(acrylicacid-b-4
      cynobiphenyl-4-oxyundecylacrylate) (PAA-b-LCP) at the aqueous/5CB interface and
      immobilizing glucose oxidase (GOx) covalently to the PAA chains. The glucose was
      detected from a homeotropic to planar orientational transition of 5CB by
      polarized optical microscopy under crossed polarizers. The maximum immobilization
      density of the GOx, 1.3 molecules/nm(2) obtained in this TEM grid cell enabled
      the detection of glucose at concentrations as low as 0.02 mM with a response time
      of 10 s. This liquid crystal-based glucose sensor provided a linear response of
      birefringence of the 5CB to glucose concentrations ranging from 0.05 to 2 mM with
      a Michaelis-Menten constant (Km) of 0.32 mM. This new and sensitive glucose
      biosensor has the merits of low production cost and easy detection through the
      naked eye and might be useful for prescreening the glucose level in the human
      body. 

PMID- 24432735
TI  - Ultrathin gold nanoribbons synthesized within the interior cavity of a self
      assembled peptide nanoarchitecture.
AB  - There is increasing interest in gold nanocrystals due to their unique physical,
      chemical, and biocompatible properties. In order to develop a template-assisted
      method for the fabrication of gold nanocrystals, we demonstrate here the de novo
      design and synthesis of a beta-sheet-forming nonapeptide (RU006: Ac-AIAKAXKIA
      NH2, X = L-2-naphthylalanine) which undergoes self-assembly to form disk-like
      nanoarchitectures approximately 100 nm wide and 2.5 nm high. These self
      assemblies tend to form a network of higher-order assemblies in ultrapure water.
      Using RU006 as a template molecule, we fabricated ultrathin gold nanoribbons 50
      100 nm wide, 2.5 nm high, and micrometers long without external reductants.
      Furthermore, in order to determine the mechanism of ultrathin gold nanoribbon
      formation, we synthesized four different RU006 analogues. On the basis of the
      results obtained using RU006 and these analogues, we propose the following
      mechanism for the self-assembly of RU006. First, RU006 forms a network by the
      cooperative association of disk-like assemblies in the presence of AuCl4(-) ions
      that are encapsulated and concentrated within the interior cavity of the network
      architectures. This is followed by electron transfer from the naphthalene rings
      to Au(III), resulting in slow growth to form ultrathin gold nanoribbons along the
      template network architectures under ambient conditions. The resulting ribbons
      retain the dimensions of the cavity of the template architecture. Our approach
      will allow the construction of diverse template architectural morphologies and
      will find applications in the construction of a variety of metallic
      nanoarchitectures.

PMID- 24432736
TI  - A new inositol triester from Taraxacum mongolicum.
AB  - One new inositol triester, 4,5,6-tri-O-p-hydroxyphenylacetyl-chiro-inositol (1),
      was isolated from the ethanolic extract of Taraxacum mongolicum, along with two
      known compounds, 11beta,13-dihydrotaraxinic acid (2) and taraxinic acid beta-d
      glucopyranosyl ester (3). The isolates were tested for their anti-hepatitis B
      virus (HBV) activities; 11beta,13-dihydrotaraxinic acid (2) exhibited an IC50
      value of 0.91 mM inhibiting the secretion of the HBV surface antigen and an IC50
      value of 0.34 mM inhibiting the secretion of the HBV e antigen using HBV
      transfected Hep G2.2.15 cell line. 

PMID- 24432739
TI  - Periodically clickable polyesters: study of intrachain self-segregation induced
      folding, crystallization, and mesophase formation.
AB  - A series of polyesters based on 2-propargyl-1,3-propanediol or 2,2-dipropargyl
      1,3-propanediol or 2-allyl-2-propargyl-1,3-propanediol and 1,20-eicosanedioic
      acid were prepared by solution polycondensation using the corresponding diacid
      chloride; these polyesters were quantitatively "clicked" with a fluoroalkyl
      azide, namely CF3(CF2)7CH2CH2N3, to yield polyesters carrying long-chain alkylene
      segments in the backbone and either one or two perfluoroalkyl segments located at
      periodic intervals along the polymer chain. The immiscibility of the alkylene and
      fluoroalkyl segments causes the polymer chains to fold in a zigzag fashion to
      facilitate the segregation of these segments; the folded chains further organize
      in the solid state to form a lamellar structure with alternating domains of alkyl
      (HC) and fluoroalkyl (FC) segments. Evidence for the self-segregation is provided
      by DSC, SAXS, WAXS, and TEM studies; in two of the samples, the DSC thermograms
      showed two distinct endotherms associated with the melting of the individual
      domains, while the WAXS patterns confirm the existence of two separate peaks
      corresponding to the interchain distances within the crystalline lattices of the
      HC and FC domains. SAXS data, on the other hand, reveal the formation of an
      extended lamellar morphology with an interlamellar spacing that matches
      reasonably well with those estimated from TEM studies. Interestingly, a smectic
      type liquid crystalline phase is observed at temperatures between the two melting
      transitions. These systems present a unique opportunity to develop interesting
      nanostructured polymeric materials with precise control over both the domain size
      and morphology; importantly, the domain sizes are far smaller than those
      typically observed in traditional block copolymers. 

PMID- 24432740
TI  - Hyaluronic acid based materials for scaffolding via two-photon polymerization.
AB  - Hydrogels are able to mimic the basic three-dimensional (3D) biological,
      chemical, and mechanical properties of native tissues. Since hyaluronic acid (HA)
      is a chief component of human extracellular matrix (ECM), it represents an
      extremely attractive starting material for the fabrication of scaffolds for
      tissue engineering. Due to poor mechanical properties of hydrogels, structure
      fabrication of this material class remains a major challenge. Two-photon
      polymerization (2PP) is a promising technique for biomedical applications, which
      allows the fabrication of complex 3D microstructures by moving the laser focus in
      the volume of a photosensitive material. Chemical modification of hyaluronan
      allows application of the 2PP technique to this natural material and, thus,
      precise fabrication of 3D hydrogel constructs. To create materials with tailor
      made mechanochemical properties, HA was combined and covalently cross-linked with
      poly(ethylene glycol) diacrylate (PEGDA) in situ. 2PP was applied for the
      fabrication of well elaborated 3D HA and HA-PEGDA microstructures. For enhanced
      biological adaption, HA was functionalized with human epidermal growth factor. 

PMID- 24432741
TI  - Cationic cyclizations and rearrangements promoted by a heterogeneous gold
      catalyst.
AB  - A heterogeneous gold catalyst with remarkable activity for promoting the
      electrophilic reactions of aryl vinyl ketones and aryl dienyl ketones is
      described. The catalyst is easy to prepare, is robust, and can be recycled. Low
      loadings are effective for different types of cationic reactions, including
      Nazarov cyclizations, lactonizations, and [1,2] shifts. 

PMID- 24432743
TI  - Anthocyanin metabolites are abundant and persistent in human urine.
AB  - LC-MS/MS revealed that metabolites of anthocyanins (Acn) were abundant in human
      urine (n = 17) even after 5 days with no dietary Acn. After intake of 250 mL of
      blueberry juice, parent Acn were 4% and Acn metabolites were 96% of the total
      urinary Acn for the following 24 h. Multiple reaction monitoring revealed 226
      combinations of mass transition * retention times for known Acn and predicted Acn
      metabolites. These were dominated by aglycones, especially aglycone glucuronides.
      The diversity of Acn metabolites could include positional isomers of Acn
      conjugates and chalcones. The persistence of Acn metabolites suggested
      enterohepatic recycling leading to prolonged residence time. The prevalence of
      Acn metabolites based on pelargonidin, which is not present in blueberry juice,
      may reflect ongoing dehydroxylation and demethylation of other Acn via xenobiotic
      and colonic bacterial action. The results suggest that exposure to Acn-based
      flavonoid moieties is substantially greater than suggested by earlier research. 

PMID- 24432744
TI  - Fe(HSO4)3/SiO2: an efficient and heterogeneous catalyst for one-pot synthesis of
      2-aryl-chromene-4-ones (flavanones).
AB  - Silica ferric hydrogensulphate is an efficient heterogeneous catalyst for
      cyclisation of 2-hydroxychalcones to their corresponding flavanones (chromanone).
      This intramolecular oxa-Michael reaction was carried out in high yields in the
      presence of electron donating and electron withdrawing groups in the chalcone
      structure. Also, we found that aniline can act as an organic co-catalyst in
      direct synthesis of flavanones from 2-hydroxyacethophenone and aldehydes in the
      presence of Fe(HSO4)3/SiO2. Flavanones were prepared in high yields in a new
      catalytic system with similar substituted effect in the indirect cyclisation
      method. The catalyst in all the above reactions is reusable without significant
      decreases in its activity after four times of recycling. 

PMID- 24432748
TI  - Probing and perturbing stem cells with chemical biology.

PMID- 24432753
TI  - The International Chemical Biology Society's global mission crystallizes in
      Kyoto.

PMID- 24432752
TI  - Bioorthogonal reactions for labeling proteins.

PMID- 24432754
TI  - An overview of Australia's compound management facility: the Queensland Compound
      Library.

PMID- 24432758
TI  - Using dimers to measure biosignatures and atmospheric pressure for terrestrial
      exoplanets.
AB  - We present a new method to probe atmospheric pressure on Earth-like planets using
      (O2-O2) dimers in the near-infrared. We also show that dimer features could be
      the most readily detectable biosignatures for Earth-like atmospheres and may even
      be detectable in transit transmission with the James Webb Space Telescope (JWST).
      The absorption by dimers changes more rapidly with pressure and density than that
      of monomers and can therefore provide additional information about atmospheric
      pressures. By comparing the absorption strengths of rotational and vibrational
      features to the absorption strengths of dimer features, we show that in some
      cases it may be possible to estimate the pressure at the reflecting surface of a
      planet. This method is demonstrated by using the O2 A band and the 1.06 MUm dimer
      feature, either in transmission or reflected spectra. It works best for planets
      around M dwarfs with atmospheric pressures between 0.1 and 10 bar and for O2
      volume mixing ratios above 50% of Earth's present-day level. Furthermore, unlike
      observations of Rayleigh scattering, this method can be used at wavelengths
      longer than 0.6 MUm and is therefore potentially applicable, although
      challenging, to near-term planet characterization missions such as JWST. We also
      performed detectability studies for JWST transit transmission spectroscopy and
      found that the 1.06 and 1.27 MUm dimer features could be detectable (SNR>3) for
      an Earth analogue orbiting an M5V star at a distance of 5 pc. The detection of
      these features could provide a constraint on the atmospheric pressure of an
      exoplanet and serve as biosignatures for oxygenic photosynthesis. We calculated
      the required signal-to-noise ratios to detect and characterize O2 monomer and
      dimer features in direct imaging-reflected spectra and found that signal-to-noise
      ratios greater than 10 at a spectral resolving power of R=100 would be required.

PMID- 24432759
TI  - Highly efficient preparation of selectively isotope cluster-labeled long chain
      fatty acids via two consecutive C(sp3)-C(sp3) cross-coupling reactions.
AB  - An efficient synthesis involving two copper-catalyzed alkyl-alkyl coupling
      reactions has been designed to easily access doubly isotope-labeled fatty acids.
      Such NMR- and IR-active compounds were obtained in excellent overall yields and
      will be further used for determining the conformation of an alkyl chain of
      lipidic biomolecules upon interaction with proteins. 

PMID- 24432760
TI  - Designing cell-aggregating peptides without cytotoxicity.
AB  - We have designed alpha-helical peptides de novo that can induce aggregation of
      various kinds of cells by focusing on physicochemical properties such as
      hydrophobicity, net charges, and amphipathicity. It is shown that peptide
      hydrophobicity is the key factor to determine capabilities for cell aggregation
      while peptide net charges contribute to nonspecific electrostatic interactions
      with cells. On the other hand, amphipathic peptides tend to exhibit cytotoxicity
      such as antimicrobial activity and hemolysis, which are competitive with cell
      aggregation capabilities. Different from the cases of living cells, aggregation
      of artificial anionic liposomes appears to be mainly determined by electrostatic
      interactions. This discrepancy might be due to the complex structure of surfaces
      of cell membranes consisting of macromolecular chains such as peptidoglycans,
      polysaccharides, or glycocalyx, which coexist with lipid bilayers. Our design
      strategy would pave the way to design peptides that lead aggregation of living
      cells without cytotoxicity. 

PMID- 24432761
TI  - New strategy for surface functionalization of periodic mesoporous silica based on
      meso-HSiO1.5.
AB  - Organic functionalization of periodic mesoporous silicas (PMSs) offers a way to
      improve their excellent properties and wide applications owing to their
      structural superiority. In this study, a new strategy for organic
      functionalization of PMSs is demonstrated by hydrosilylation of the recently
      discovered "impossible" periodic mesoporous hydridosilica, meso-HSiO1.5. This
      method overcomes the disadvantages of present pathways for organic
      functionalization of PMSs with organosilica. Moreover, compared to the
      traditional functionalization on the surface of porous silicon by
      hydrosilylation, the template-synthesized meso-HSiO1.5 is more flexible to access
      functional-groups-loaded PMSs with adjustable microstructures. The new method and
      materials will have wider applications based on both the structure and surface
      superiorities. 

PMID- 24432762
TI  - Crystalline carbon nitride nanosheets for improved visible-light hydrogen
      evolution.
AB  - Nanosheets of a crystalline 2D carbon nitride were obtained by ionothermal
      synthesis of the layered bulk material poly(triazine imide), PTI, followed by one
      step liquid exfoliation in water. Triazine-based nanosheets are 1-2 nm in height
      and afford chemically and colloidally stable suspensions under both basic and
      acidic conditions. We use solid-state NMR spectroscopy of isotopically enriched,
      restacked nanosheets as a tool to indirectly monitor the exfoliation process and
      carve out the chemical changes occurring upon exfoliation, as well as to
      determine the nanosheet thickness. PTI nanosheets show significantly enhanced
      visible-light driven photocatalytic activity toward hydrogen evolution compared
      to their bulk counterpart, which highlights the crucial role of morphology and
      surface area on the photocatalytic performance of carbon nitride materials. 

PMID- 24432763
TI  - Factors affecting skin tannin extractability in ripening grapes.
AB  - The acetone-extractable (70% v/v) skin tannin content of Vitis vinifera L. cv.
      Cabernet Sauvignon grapes was found to increase during late-stage ripening.
      Conversely, skin tannin content determined following ethanol extraction (10, 20,
      and 50% v/v) did not consistently reflect this trend. The results indicated that
      a fraction of tannin became less extractable in aqueous ethanol during ripening.
      Skin cell walls were observed to become more porous during ripening, which may
      facilitate the sequestering of tannin as an adsorbed fraction within cell walls.
      For ethanol extracts, tannin molecular mass increased with advancing ripeness,
      even when extractable tannin content was constant, but this effect was negligible
      in acetone extracts. Reconstitution experiments with isolated skin tannin and
      cell wall material indicated that the selectivity of tannin adsorption by cell
      walls changed as tannin concentration increased. Tannin concentration, tannin
      molecular mass, and cell wall porosity are discussed as factors that may
      influence skin tannin extractability. 

PMID- 24432764
TI  - The essential oil composition of aerial parts of Anthemis tricolor Boiss. from
      Cyprus.
AB  - The water-distilled essential oil from the aerial parts of Anthemis tricolor
      Boiss. (Asteraceae), an endemic taxon from Cyprus, was analysed by GC and GC-MS.
      The analysis revealed 40 compounds accounting for 84.5% of the oil. Muurola-4,11
      diene (20.2%), beta-caryophyllene (9.1%) and germacrene-D (5.5%) were the main
      compounds of A. tricolor. To the best of our knowledge, this is the first
      detailed study of the essential oil composition of A. tricolor collected from
      Cyprus. 

PMID- 24432768
TI  - 3-Alkenyl-2-silyloxyindoles in vinylogous Mannich reactions: synthesis of
      aminated indole-based scaffolds and products.
AB  - The first Lewis acid catalyzed vinylogous Mukaiyama-type Mannich addition of 3
      alkenyl-2-silyloxyindoles to in situ generated N-Boc imines has been established,
      which affords chiral alpha-alkylidene-delta-amino-2-oxindole products with good
      efficiency and complete gamma-site- and Z-selectivity. The reaction is wide in
      scope, as it can be applied with equal convenience to different silyloxyindole
      donors and aromatic or aliphatic aminal-derived aldimine acceptors. The utility
      of these scaffolds is demonstrated by their easy transformation into either
      spirocyclopropane oxindole or homotryptamine-like products, featuring
      nontraditional indole-based skeleton connections. 

PMID- 24432774
TI  - Challenges in implementing a screening method for veterinary drugs in milk using
      liquid chromatography quadrupole time-of-flight mass spectrometry.
AB  - High resolution mass spectrometry (HRMS) is a valuable tool for the analysis of
      chemical contaminants in food. Our laboratory has successfully developed methods
      to screen for veterinary drug residues using liquid chromatography quadrupole
      time-of-flight (Q-TOF). There have been, however, significant challenges as
      methods are transferred from the development stage to routine regulatory
      analysis. Having experimental retention time and product ion information for
      analytes greatly facilitates the ability to determine if residues found by the
      HRMS searching software are false detects. These data were collected for over 200
      veterinary drug residues using LC Q-TOF MS. The screening levels of detection for
      over 150 veterinary drug residues in milk were determined, and over half of those
      tested can be detected at concentrations of 10 ng/mL or less; 72% can be found in
      milk when present at 100 ng/mL. Tentative identification of the product ions from
      these analytes is also presented. 

PMID- 24432775
TI  - A genetic inventory of spacecraft and associated surfaces.
AB  - Terrestrial organisms or other contaminants that are transported to Mars could
      interfere with efforts to study the potential for indigenous martian life.
      Similarly, contaminants that make the round-trip to Mars and back to Earth could
      compromise the ability to discriminate an authentic martian biosignature from a
      terrestrial organism. For this reason, it is important to develop a comprehensive
      inventory of microbes that are present on spacecraft to avoid interpreting their
      traces as authentic extraterrestrial biosignatures. Culture-based methods are
      currently used by NASA to assess spacecraft cleanliness but deliberately detect
      only a very small subset of total organisms present. The National Research
      Council has recommended that molecular (DNA)-based identification techniques
      should be developed as one aspect of managing the risk that terrestrial
      contamination could interfere with detection of life on (or returned from) Mars.
      The current understanding of the microbial diversity associated with spacecraft
      and clean room surfaces is expanding, but the capability to generate a
      comprehensive inventory of the microbial populations present on spacecraft
      outbound from Earth would address multiple considerations in planetary
      protection, relevant to both robotic and human missions. To this end, a 6-year
      genetic inventory study was undertaken by a NASA/JPL team. It was completed in
      2012 and included delivery of a publicly available comprehensive final report.
      The genetic inventory study team evaluated the utility of three analytical
      technologies (conventional cloning techniques, PhyloChip DNA microarrays, and 454
      tag-pyrosequencing) and combined them with a systematic methodology to collect,
      process, and archive nucleic acids as the first steps in assessing the
      phylogenetic breadth of microorganisms on spacecraft and associated surfaces.

PMID- 24432776
TI  - Implementing planetary protection measures on the Mars Science Laboratory.
AB  - The Mars Science Laboratory (MSL), comprising a cruise stage; an aeroshell; an
      entry, descent, and landing system; and the radioisotope thermoelectric generator
      powered Curiosity rover, made history with its unprecedented sky crane landing on
      Mars on August 6, 2012. The mission's primary science objective has been to
      explore the area surrounding Gale Crater and assess its habitability for past
      life. Because microbial contamination could profoundly impact the integrity of
      the mission and compliance with international treaty was required, planetary
      protection measures were implemented on MSL hardware to verify that bioburden
      levels complied with NASA regulations. By applying the proper antimicrobial
      countermeasures throughout all phases of assembly, the total bacterial endospore
      burden of MSL at the time of launch was kept to 2.78*105 spores, well within the
      required specification of less than 5.0*105 spores. The total spore burden of the
      exposed surfaces of the landed MSL hardware was 5.64*104, well below the allowed
      limit of 3.0*105 spores. At the time of launch, the MSL spacecraft was burdened
      with an average of 22 spores/m2, which included both planned landed and planned
      impacted hardware. Here, we report the results of a campaign to implement and
      verify planetary protection measures on the MSL flight system.

PMID- 24432777
TI  - Implementing planetary protection on the Atlas V fairing and ground systems used
      to launch the Mars Science Laboratory.
AB  - On November 26, 2011, the Mars Science Laboratory (MSL) launched from Florida's
      Cape Canaveral Air Force Station aboard an Atlas V 541 rocket, taking its first
      step toward exploring the past habitability of Mars' Gale Crater. Because
      microbial contamination could profoundly impact the integrity of the mission, and
      compliance with international treaty was a necessity, planetary protection
      measures were implemented on all MSL hardware to verify that bioburden levels
      complied with NASA regulations. The cleanliness of the Atlas V payload fairing
      (PLF) and associated ground support systems used to launch MSL were also
      evaluated. By applying proper recontamination countermeasures early and often in
      the encapsulation process, the PLF was kept extremely clean and was shown to pose
      little threat of recontaminating the enclosed MSL flight system upon launch.
      Contrary to prelaunch estimates that assumed that the interior PLF spore burden
      ranged from 500 to 1000 spores/m2, the interior surfaces of the Atlas V PLF were
      extremely clean, housing a mere 4.65 spores/m2. Reported here are the practices
      and results of the campaign to implement and verify planetary protection measures
      on the Atlas V launch vehicle and associated ground support systems used to
      launch MSL. All these facilities and systems were very well kept and exceeded the
      levels of cleanliness and rigor required in launching the MSL payload.

PMID- 24432778
TI  - Hb Memphis [HBA2: c.70G>C (or HBA1)] in a Turkish child: a case report and
      comparison to Hb Q-Thailand (HBA1: c.223G>C).
AB  - Hb Memphis [alpha23(B4)Glu->Gln; HBA2: c.70G > C (or HBA1)] is a stable
      hemoglobin (Hb) variant caused by a substitution of glutamine for glutamic acid
      at residue 23 of the alpha2- or alpha1-globin chain. Heterozygous Hb Memphis has
      no known clinical or hematological effect, and all prior reports have resulted
      from observations in persons of African descent with sickle cell disease and an
      unusually mild clinical course. Family studies suggest that Hb Memphis may
      modulate sickling. Only brief characterizations of Hb Memphis trait in the
      absence of Hb S are present in the current literature. We report isolated Hb
      Memphis trait in Turkish individuals in whom the initial laboratory incorrectly
      identified the alpha variant as Q-Thailand [alpha74(EF3)Asp->His; HBA1: c.223G >
      C]. In one case, a heterozygous -3.7 kb alpha gene deletion was also present,
      which increased the variant Hb level to a percentage similar to that of the more
      common Hb Q-Thailand, which may have led to the misidentification. Herein, we
      discuss the characterization and comparison of these variants and underscore the
      necessity of confirming characterization by more than one method prior to
      assigning Hb variant identification.

PMID- 24432779
TI  - Template synthesis of gold nanoparticles with an organic molecular cage.
AB  - We report a novel strategy for the controlled synthesis of gold nanoparticles
      (AuNPs) with narrow size distribution (1.9 +/- 0.4 nm) through NP nucleation and
      growth inside the cavity of a well-defined three-dimensional, shape-persistent
      organic molecular cage. Our results show that both a well-defined cage structure
      and pendant thioether groups pointing inside the cavity are essential for the
      AuNP synthesis. 

PMID- 24432781
TI  - Hereditary angioedema: a brief review of new developments.
AB  - BACKGROUND: Angioedema is a serious medical condition characterized by recurrent
      non-pitting tissue edema. Hereditary (HAE) forms of this disorder are potentially
      fatal. METHODS: PubMED, Up to Date and Cochrane Library databases were used to
      identify scholarly peer reviewed original research or review articles on
      angioedema. Search terms used were: angioedema, HAE, ACE inhibitor induced
      angioedema, acquired angioedema, type III HAE (now termed HAE with normal C1
      INH), diagnosis of HAE, and treatment of HAE. Inclusive dates of the search were
      1946 through 2013. Articles on urticaria were excluded. RESULTS: The
      pathophysiology, clinical manifestations, differential diagnosis and treatments
      of angioedema are presented. Three variants of HAE are discussed and
      differentiated from acquired, ACE induced and allergic types of angioedema.
      Emphasis is placed on understanding that HAE is mediated by bradykinin, not
      histamine, and is therefore unresponsive to antihistamines, corticosteroids and
      epinephrine. In contrast, newer therapies that replace C1-INH or block bradykinin
      production or action are the appropriate treatments for prophylaxis and acute
      treatment of HAE. CONCLUSION: Recognition of HAE by primary care providers and
      distinguishing it from allergic histamine mediated angioedema is essential in
      preventing recurrent attacks and avoiding inappropriate therapy, and may be life
      saving.

PMID- 24432786
TI  - Substrate control in enantioselective and diastereoselective aldol reaction by
      memory of chirality: a rapid access to enantiopure beta-hydroxy quaternary alpha
      amino acids.
AB  - An asymmetric aldol reaction by memory of chirality is reported with a substrate
      control of stereoselectivity by aldehyde and rationalized. Starting from l
      alanine, several diastereopure and enantioenriched beta-hydroxy quaternary alpha
      amino acids have been obtained in three steps. The initial chirality of l-alanine
      is memorized through the dynamic axial chirality of tertiary aromatic amide. 

PMID- 24432787
TI  - Adhesion between glass fiber posts and resin cement: evaluation of bond strength
      after various pre-treatments.
AB  - PURPOSE: To evaluate surface roughness and bond strength of glass fiber posts to
      a resin cement after various surface treatments. MATERIALS AND METHODS: Sixty
      individually formed glass fiber posts with a diameter of 1.5 mm and a length of
      20 mm were used for this study. They were randomly assigned to six groups of pre
      treatment (n = 10/group): Group C, untreated (control); Group SB, sandblasted;
      Group SC, silica coated; Group HF, hydrofluoric acid-etched; Group N, Nd:YAG
      laser irradiated; Group E, Er:YAG laser irradiated. Surface roughness of the
      posts was measured before and after pre-treatment. The posts were then bonded to
      resin cement and tensile bond strengths were determined in a universal testing
      machine. For statistical analysis, two-way ANOVA and post-hoc comparison tests
      (alpha = 0.05) were performed. RESULTS: The highest bond strength value was
      observed in group HF, followed by group SC. There was a statistically significant
      difference in bond strength between group C and groups HF, SC and E (p < 0.001, p
      = 0.002 and p = 0.041, respectively). Posts of group SB and group N showed the
      highest surface roughness. CONCLUSIONS: The findings of the present study reveal
      that hydrofluoric acid-etching, silica coating and Er:YAG laser irradiation
      provided a significant increase in bond strength between glass fiber posts and
      resin cement.

PMID- 24432788
TI  - Dental erosion: a widespread condition nowadays? A cross-sectional study among a
      group of adolescents in Norway.
AB  - OBJECTIVE: This study aimed to investigate the prevalence, distribution and
      severity of erosive wear in a group of 16-18-year-olds in the western part of
      Norway. A second aim was to describe possible associations between caries
      experience, socioeconomic background and origin of birth. MATERIALS AND METHODS:
      Adolescents (n = 795) attending recall examinations at Public Dental Service
      (PDS) clinics were also examined for dental erosive wear on index surfaces, using
      the Visual Erosion Dental Examination scoring system (VEDE). RESULTS: In total,
      795 individuals were examined. Dental erosive wear was diagnosed in 59% of the
      population (44% erosive wear in enamel only, 14% combination of enamel and
      dentine lesions, 1% erosive wear in dentine only). The palatal surfaces of upper
      central incisors and occlusal surfaces of first lower molars were affected the
      most (33% and 48% of all surfaces, respectively). Cuppings on molars were
      registered in 66% of the individuals with erosive wear. Erosive wear was
      significantly more prevalent among men (63%) than women (55%) (p = 0.018).
      CONCLUSIONS: There were no significant associations between dental erosive wear
      and caries experience, socioeconomic background or origin of birth.

PMID- 24432789
TI  - Dendrimer-assisted formation of fluorescent nanogels for drug delivery and
      intracellular imaging.
AB  - Although, in general, nanogels present a good biocompatibility and are able to
      mimic biological tissues, their unstability and uncontrollable release properties
      still limit their biomedical applications. In this study, a simple approach was
      used to develop dual-cross-linked dendrimer/alginate nanogels (AG/G5), using
      CaCl2 as cross-linker and amine-terminated generation 5 dendrimer (G5) as a
      cocrosslinker, through an emulsion method. Via their strong electrostatic
      interactions with anionic AG, together with cross-linker Ca(2+), G5 dendrimers
      can be used to mediate the formation of more compact structural nanogels with
      smaller size (433 +/- 17 nm) than that (873 +/- 116 nm) of the Ca(2+)-cross
      linked AG nanogels in the absence of G5. Under physiological (pH 7.4) and acidic
      (pH 5.5) conditions, the sizes of Ca(2+)-cross-linked AG nanogels gradually
      decrease probably because of their degradation, while dual-cross-linked AG/G5
      nanogels maintain a relatively more stable structure. Furthermore, the AG/G5
      nanogels effectively encapsulate the anticancer drug doxorubicin (Dox) with a
      loading capacity 3 times higher than that of AG nanogels. The AG/G5 nanogels were
      able to release Dox in a sustained way, avoiding the burst release observed for
      AG nanogels. In vitro studies show that the AG/G5-Dox NGs were effectively taken
      up by CAL-72 cells (a human osteosarcoma cell line) and maintain the anticancer
      cytotoxicity levels of free Dox. Interestingly, G5 labeled with a fluorescent
      marker can be integrated into the nanogels and be used to track the nanogels
      inside cells by fluorescence microscopy. These findings demonstrate that AG/G5
      nanogels may serve as a general platform for therapeutic delivery and/or cell
      imaging. 

PMID- 24432790
TI  - Including explicit water molecules as part of the protein structure in MM/PBSA
      calculations.
AB  - Water is the natural medium of molecules in the cell and plays an important role
      in protein structure, function and interaction with small molecule ligands.
      However, the widely used molecular mechanics Poisson-Boltzmann surface area
      (MM/PBSA) method for binding energy calculation does not explicitly take account
      of water molecules that mediate key protein-ligand interactions. We have
      developed a protocol to include water molecules that mediate ligand-protein
      interactions as part of the protein structure in calculation of MM/PBSA binding
      energies (a method we refer to as water-MM/PBSA) for a series of JNK3 kinase
      inhibitors. Improved correlation between water-MM/PBSA binding energies and
      experimental IC50 values was obtained compared to that obtained from classical
      MM/PBSA binding energy. This improved correlation was further validated using
      sets of neuraminidase and avidin inhibitors. The observed improvement, however,
      appears to be limited to systems in which there are water-mediated ligand-protein
      hydrogen bond interactions. We conclude that the water-MM/PBSA method performs
      better than classical MM/PBSA in predicting binding affinities when water
      molecules play a direct role in mediating ligand-protein hydrogen bond
      interactions.

PMID- 24432791
TI  - Single electron pnicogen bonded complexes.
AB  - A theoretical study of the complexes formed by monosubstituted phosphines (XH2P)
      and the methyl radical (CH3) has been carried out by means of MP2 and CCSD(T)
      computational methods. Two minima configurations have been obtained for each
      XH2P:CH3 complex. The first one shows small P-C distances and, in general, large
      interaction energies. It is the most stable one except in the case of the H3P:CH3
      complex. The second minimum where the P-C distance is large and resembles a
      typical weak pnicogen bond interaction shows interaction energies between -9.8
      and -3.7 kJ mol(-1). A charge transfer from the unpaired electron of the methyl
      radical to the P-X sigma* orbital is responsible for the interaction in the
      second minima complexes. The transition state (TS) structures that connect the
      two minima for each XH2P:CH3 complex have been localized and characterized. 

PMID- 24432794
TI  - The role of intra-arterial chemotherapy as an adjuvant treatment for
      glioblastoma.
AB  - Glioblastoma multiforme (GBM) is an aggressive tumor with poor survival outcomes
      and limited treatment options. We conducted a literature review to compare the
      survival outcomes of intra-arterial (IA) and intravenous (IV) chemotherapy
      delivery for GBM. Nine studies of IA chemotherapy infusion with 301 total
      patients met our criteria for inclusion and three studies contained IV treatment
      groups for comparison (n = 230 for IA, n = 71 for IV). The studies were grouped
      by either using newly diagnosed or recurrent GBM patients. In the newly diagnosed
      group, IV chemotherapy produced a statistically higher median overall survival
      (MOS; 16.3 months) compared with IA treatment (14.02 months). However, the total
      number of adverse events in IA chemotherapy was 1.08 per patient whereas for IV
      it was higher at 1.54 events per patient. Our recurrent GBM group includes only
      patients treated with IA chemotherapy which resulted in an average MOS of 10.84
      months. This group had 2.7 adverse events per patient but no IV group is
      available for comparison. Historically, the survival of patients with recurrent
      GBM ranges from 3 to 9 months (Gil-Gil et al. Bevacizumab for the treatment of
      glioblastoma. Clin Med Insights Oncol 2013;7:123-35). For this reason, we believe
      IA chemotherapy to be a viable methodology in recurrent GBM patients to prolong
      survival at the risk of procedure-related complications and in newly diagnosed
      patients with the benefit of decreased complications.

PMID- 24432796
TI  - A systematic literature review of methodologies used to assess medication
      adherence in patients with diabetes.
AB  - OBJECTIVE: Adhering to prescribed medication is often a problem for patients with
      diabetes yet there is no consensus on how best to measure adherence in this
      patient population. This systematic literature review critically reviewed and
      summarized the methods used to measure medication adherence in patients with
      diabetes (on oral hypoglycemic agents [OHAs] and/or insulin) in original research
      published between 2007-2013. STUDY DESIGN: Literature review. METHODS: A
      systematic search for methods to assess medication adherence in patients with
      type I or type II diabetes was conducted using PubMed, EMBASE, PsychInfo, and
      Cochrane databases. Two researchers independently screened abstracts for initial
      eligibility and then applied the inclusion/exclusion criteria to the relevant
      full-text articles. RESULTS: Fifty-nine articles met the criteria for inclusion.
      Subjective assessment (observer-reported and patient-reported), pill counts,
      Medication Event Monitoring System (MEMS), cell-phone real-time assessment, and
      logbooks were used in prospective studies. In pharmacy claims databases,
      medication possession ratios (MPRs), or some derivation thereof, were utilized.
      Each method has strengths and weaknesses, but few approaches specifically
      addressed issues unique to assessing insulin adherence. Three novel approaches
      (using cell-phone real-time assessment, computerized logbooks, and a
      questionnaire about different dosing irregularities) provided insight on timing
      and dosing issues that could be useful for highlighting interventions to improve
      insulin adherence. CONCLUSION: No gold standard exists for measuring medication
      adherence in patients with diabetes. The plethora of adherence methods precludes
      the comparison of adherence rates across studies. Greater consistency is
      therefore needed in adherence measurement, including question content, recall
      period, and response options for self-report measures. Novel methods for
      understanding adherence to variable-dosed insulin require further research.
      Researchers should select a methodology that best fits their research question,
      study design, patient population and resources.

PMID- 24432797
TI  - Activation of aryl halides at gold(I): practical synthesis of (P,C)
      cyclometalated gold(III) complexes.
AB  - Taking advantage of phosphine chelation, direct evidence for oxidative addition
      of Csp(2)-X bonds (X = I, Br) to a single gold atom is reported. NMR studies and
      DFT calculations provide insight into this unprecedented transformation, which
      gives straightforward access to stable (P,C) cyclometalated gold(III) complexes. 

PMID- 24432798
TI  - Dearomatization strategy and palladium-catalyzed domino reaction: construction of
      azepino[5,4,3-cd]indoles from 2-alkynylanilines.
AB  - A facile approach to construct 3,4-fused tricyclic azepino[5,4,3-cd]indoles from
      2-alkynyl anilines, isocyanides, and alpha,beta-unsaturated acids is reported.
      This synthetic process involves a regioselective meta-functionalization of 2
      alkynylanilines using a dearomatization strategy and a palladium(II)-catalyzed
      domino heterocyclization/Heck reaction. 

PMID- 24432800
TI  - Patient age is related to the types of physical therapy interventions provided
      for chronic low back pain: an observational study.
AB  - STUDY DESIGN: Retrospective analysis of a longitudinal cohort of patients treated
      for chronic low back pain (CLBP). OBJECTIVES: To determine whether patient age is
      associated with types of physical therapy interventions received for CLBP.
      BACKGROUND: Advancing age is associated with less positive treatment outcomes in
      patients with CLBP. If patient age influences a therapist's choice of
      interventions, it may partially explain the difference in treatment outcomes.
      METHODS: Data were examined in a sample of 7392 patients (62% women, 38% men;
      mean +/- SD age, 56.7 +/- 16.5 years) with CLBP. We used a generalized estimating
      equation to examine the probability of each subject receiving each of the
      individual intervention categories in the presence of the other intervention
      categories. RESULTS: A significant interaction between intervention category and
      age existed after controlling for gender, duration of symptoms, comorbidities,
      payer source, and functional status at initial intake (chi(2) = 130.27, df = 8,
      P<.0001). The changes in probability of receiving an intervention category
      averaged 10% as patient age increased. The probability of receiving exercise or
      task-specific training did not change with advancing age. The probability of
      receiving postural exercises, pain modalities, joint mobility techniques, ice, or
      McKenzie exercises decreased with advancing age. The probability of receiving
      augmented soft tissue mobilization and balance/mobility training increased as age
      increased. CONCLUSION: The impact of age on physical therapist treatment choices
      varies depending on the type of intervention. Other variables in addition to age
      may have an impact on treatment choice. Further research is needed to determine
      how therapists incorporate age into their clinical decision making.

PMID- 24432801
TI  - Hb Grand Junction (HBB: c.348_349delinsG; p.His117IlefsX42): a new hyperunstable
      hemoglobin variant.
AB  - Hyperunstable hemoglobinopathy (HUH) [dominantly inherited beta-thalassemia (beta
      thal)] is a relatively rare form of congenital hemolytic anemia in which
      mutations occur in the genes encoding for alpha and beta chains, or both chains
      of the hemoglobin (Hb) molecule. We describe two Hispanic adolescents with a new
      unstable Hb variant (HBB: c.348_349delinsG; p.His117IlefsX42), resulting from a
      frameshift mutation at codons 115/116 of the beta-globin gene. Both patients also
      have a 3.7 kb deletion on one alpha gene, leading to a decreased imbalance
      between alpha and beta chain formation, and subsequently a milder phenotype than
      that seen in other hyperunstable Hb variants.

PMID- 24432802
TI  - Molecular structures and absorption spectra assignment of corrole NH tautomers.
AB  - The individual absorption spectra of the two NH tautomers of 10-(4,6
      dichloropyrimidin-5-yl)-5,15-dimesitylcorrole are assigned on the basis of the
      Gouterman four-orbital model and a quantum chemical TD-DFT study. The assignment
      indicates that the red-shifted T1 tautomer is the one with protonated pyrrole
      nitrogen atoms N(21), N(22) and N(23), whereas the blue-shifted T2 tautomer has
      pyrrole nitrogen atoms N(21), N(22) and N(24) protonated. A wave-like nonplanar
      distortion of the macrocycle in the ground state is found for both NH tautomers,
      with the wave axis going through the pyrroles containing N(22) and N(24). The 7C
      plane determined by the least-squares distances to the carbon atoms C1, C4, C5,
      C6, C9, C16, and C19 is suggested as a mean corrole macrocycle plane for the
      analysis of out-of-plane distortions. The magnitude of these distortions is
      distinctly different for the two NH tautomers, leading to substantial
      perturbations of their acid-base properties, which are rationalized by the
      interplay of the degree of out-of-plane distortion of the macrocycle as a whole
      and the tendency of the pyrrole nitrogen atoms toward pyramidalization, with the
      former leading to a basicity increase whereas the latter enhances the acidity. 

PMID- 24432803
TI  - Effect of catheter-based renal sympathetic denervation on 24-h ambulatory blood
      pressure in patients with resistant hypertension.
AB  - We investigated the effect of renal denervation on office blood pressure (OBP)
      and 24-h ambulatory blood pressure (BP) measurement (ABPM) at baseline and 6
      months after intervention in 25 consecutive patients with resistant hypertension.
      Mean baseline 24-h ABPM and OBP were 158/88 mmHg and 169/96 mmHg, respectively.
      Patients were treated with an average of 4 +/- 1 antihypertensive drugs. Among
      the 22 patients included in data analysis, mean ambulatory systolic and diastolic
      BP were reduced by 6 mmHg from 158 +/- 17 to 152 +/- 20 mmHg (p < 0.05) and by 3
      mmHg from 88 +/- 12 to 85 +/- 14 mmHg (p = ns) after 6 months follow-up,
      respectively. Blood pressure reduction was most pronounced during daytime with a
      decrease of 9 mmHg from 164 +/- 17 to 155 +/- 19 (p < 0.05) in systolic (SBP) and
      6 mmHg from 94 +/- 14 to 88 +/- 14 mmHg in diastolic BP (DBP) (p < 0.05). Night
      time SBP mmHg and DBP were similar at baseline compared with follow-up. Systolic
      and diastolic OBP during follow-up were significantly reduced by 17 mmHg from 169
      +/- 20 to 152 +/- 21 (p < 0.05) and by 9 mmHg from 96 +/- 16 to 87 +/- 13 mmHg (p
      < 0.05), respectively. These results provide new insight into the effect of renal
      denervation on ABPM day- and night-time blood pressure profile in comparison with
      OBP. The decrease in ABPM was identified during daytime registration and was less
      pronounced compared with reduction of OBP.

PMID- 24432804
TI  - Evaluation of 3D printing and its potential impact on biotechnology and the
      chemical sciences.
AB  - Nearing 30 years since its introduction, 3D printing technology is set to
      revolutionize research and teaching laboratories. This feature encompasses the
      history of 3D printing, reviews various printing methods, and presents current
      applications. The authors offer an appraisal of the future direction and impact
      this technology will have on laboratory settings as 3D printers become more
      accessible. 

PMID- 24432813
TI  - Myrifabine, the first dimeric Myrioneuron alkaloid from Myrioneuron faberi.
AB  - One Myrioneuron alkaloid, myrifabine (1), the first example of a dimer with 12
      chiral centers embraced in a decacyclic novel skeleton, was isolated from
      Myrioneuron faberi . Its structure was elucidated by spectroscopic data and
      single-crystal X-ray diffraction. The antimicrobial and cytotoxic activities of 1
      were evaluated in vitro. 

PMID- 24432806
TI  - Enzymatic surface erosion of high tensile strength polycarbonates based on
      natural phenols.
AB  - Surface erosion has been recognized as a valuable design tool for resorbable
      biomaterials within the context of drug delivery devices, surface coatings, and
      when precise control of strength retention is critical. Here we report on high
      tensile strength, aromatic-aliphatic polycarbonates based on natural phenols,
      tyrosol (Ty) and homovanillyl alcohol (Hva), that exhibit enzymatic surface
      erosion by lipase. The Young's moduli of the polymers for dry and fully hydrated
      samples are 1.0 to 1.2 GPa and 0.8 to 1.2 GPa, respectively. Typical
      characteristics of enzymatic surface erosion were confirmed for poly(tyrosol
      carbonate) films with concomitant mass-loss and thickness-loss at linear rates of
      0.14 +/- 0.01 mg cm(-2) d(-1) and 3.0 +/- 0.8 MUm d(-1), respectively. The
      molecular weight and the mechanical properties of the residual films remained
      constant. Changing the ratio of Ty and Hva provided control over the glass
      transition temperature (T(g)) and the enzymatic surface erosion: increasing the
      Hva content in the polymers resulted in higher T(g) and lower enzymatic erosion
      rate. Polymers with more than 50 mol % Hva were stable at 37  degrees C in enzyme
      solution. Analysis on thin films using quartz crystal microbalance with
      dissipation (QCM-D) demonstrated that the onset temperature of the enzymatic
      erosion was approximately 20  degrees C lower than the wet T(g) for all tested
      polymers. This new finding demonstrates that relatively high tensile strength
      polycarbonates can undergo enzymatic surface erosion. Moreover, it also sheds
      light on the connection between T(g) and enzymatic degradation and explains why
      few of the high strength polymers follow an enzyme-meditated degradation pathway.

PMID- 24432814
TI  - Regioselective synthesis of 1,3,5-trisubstituted pyrazoles from N-alkylated
      tosylhydrazones and terminal alkynes.
AB  - An efficient synthesis of 1,3,5-trisubstituted pyrazoles from N-alkylated
      tosylhydrazones and terminal alkynes was developed. The protocol was applied to a
      wide range of substrates and demonstrated excellent tolerance to a variety of
      substituents, including both electron-donating and -withdrawing groups. In
      comparison with the common approaches for substituted pyrazole syntheses, this
      methodology proceeded with complete regioselectivity, especially, in the cases
      that R(2) and R(3) are similar substituents. 

PMID- 24432815
TI  - Assessment of carotid calcifications on panoramic radiographs in relation to
      other used methods and relationship to periodontitis and stroke: a literature
      review.
AB  - OBJECTIVES: To assess the literature on carotid calcifications defined from
      panoramic radiographs (PMX) and concurrent diagnosis of stroke and periodontitis.
      MATERIALS AND METHODS: A literature search screening for publications using
      search terms such as PMX and carotid calcification, stroke and periodontitis was
      performed in November 2012. RESULTS: A total of 189 articles were retrieved,
      among which 30 were included in the review. The sensitivity for PMX findings of
      carotid calcifications (CC) compared to a diagnosis by Doppler sonography varied
      between 31.1-100%. The specificity for PMX findings of carotid calcifications
      compared to a diagnosis by Doppler sonography varied between 21.4-87.5%.
      Individuals with CC findings from PMX have more periodontitis and risk for
      stroke. CONCLUSIONS: There is a shortage of well-designed studies in older
      dentate individuals assessing the associations between periodontitis and
      radiographic evidence of CC and in relation to stroke or other cardiovascular
      diseases. STATEMENT OF CLINICAL RELEVANCE: Carotid calcifications are prevalent
      in patients with periodontitis and such individuals may have an increased risk
      for stroke. The absence of signs of carotid calcification on panoramic
      radiographs is indicative of no calcification of carotid arteries.

PMID- 24432816
TI  - Utilization of smoking-cessation pharmacotherapy among chronic obstructive
      pulmonary disease (COPD) and lung cancer patients.
AB  - OBJECTIVE: Smoking is one of the major risk factors causing morbidity and
      mortality in chronic obstructive pulmonary disease (COPD) and lung cancer
      patients. Use of smoking cessation pharmacotherapy is an effective way to help
      quit smoking. The purpose of the study was to determine the prevalence of smoking
      and the proportion of patients using smoking cessation agents, and to identify
      the socio-demographic factors that affect the use of these agents among COPD and
      lung cancer patients. RESEARCH DESIGN AND METHODS: A retrospective study was done
      to identify smokers having COPD (ICD-9: 490-492) or lung cancer (ICD-9: 162), and
      those who use smoking cessation agents from 2006-2010, using Medical Expenditure
      Panel Survey (MEPS) data. A multiple logistic regression model was built to
      identify significant socio-demographic predictors associated with the use of
      smoking cessation agents. RESULTS: Around 16.8% of COPD patients and 15.1% of
      lung cancer patients reported smoking after diagnosis. Out of the total smokers,
      8.8% patients with COPD and 12.6% patients with lung cancer reported use of
      smoking cessation agents during the 5 year period. Logistic regression showed
      that odds for smoking cessation use in COPD patients were lower for Hispanics (OR
      = 0.107, 95% CI 0.023-0.502) and higher for patients having insurance coverage
      (OR = 3.453, 95% CI 1.240-9.617). CONCLUSION: Results showed that a large number
      of patients continued to smoke even after the diagnosis of COPD and lung cancer;
      whereas only a few among them used smoking cessation agents. Ethnicity
      disparities and insurance status were associated with the use of smoking
      cessation agents. Differential use among population sub-groups suggests a
      requirement for need based smoking cessation programs and appropriate
      prescription drug coverage. Further research needs to be done to evaluate reasons
      for disparities in smoking cessation agents' use. The study had limitations
      common to research designs based on observational and self-reported datasets.

PMID- 24432817
TI  - The WHO collaborating centre for public health palliative care programs: an
      innovative approach of palliative care development.
AB  - BACKGROUND: The designation of the Catalan Institute of Oncology (Barcelona,
      Spain) as World Health Organization (WHO) Collaborating Centre for Public Health
      Palliative Care Programmes (WHOCC-ICO) in February 2008 turns the institution
      into the first ever center of international reference in regards to palliative
      care implementation from a public health perspective. The center aims to provide
      support to countries willing to develop palliative care programs, to identify
      models of success, to support WHO's policies, and to generate and spread evidence
      on palliative care. OBJECTIVE: This article describes the WHOCC-ICO's
      contribution in the implementation of public health palliative care programs and
      services. The center's main features and future actions are emphasized. RESULTS:
      At the end of the initial four-year designation period, the organization
      evaluates the task done to reach its objectives. Such global assessment would
      take forward the quality of the institution, and generate a revision of its terms
      of reference for the next designation period. CONCLUSIONS: Based on new evidence,
      the center has recently decided to expand its scope by adopting a community-wide
      chronic care approach which moves beyond cancer and focuses on the early
      identification of patients with any chronic disease in need of palliative care.
      Moreover, the center advocates the development of comprehensive models of care
      that address patients' psychosocial needs. This center's new work plan includes
      additional significant innovations, such as the startup of the first chair of
      palliative care in Spain. Such a whole new approach responds to the main
      challenges of current palliative care.

PMID- 24432818
TI  - A pilot study to evaluate symptom-oriented selection of antidepressants in
      patients with cancer.
AB  - BACKGROUND: Major depressive disorder (MDD) is a common and debilitating illness
      in patients with cancer. However, the optimal treatment of depression in these
      patients remains uncertain, with limited evidence to support the use of
      pharmacologic therapy. We conducted a pilot study to evaluate the feasibility of
      an antidepressant clinical trial in the oncology population and the process of
      symptom-oriented selection of antidepressants (citalopram or mirtazapine) in
      patients with cancer and MDD. METHODS: This was a single center, two-arm,
      nonrandomized, open-label, nine-week pilot study of mirtazapine or citalopram in
      cancer patients with MDD. The primary endpoint was the feasibility to recruit and
      to retain patients. Secondary outcomes included changes in Patient Health
      Questionnaire-9 (PHQ-9) (depression), Functional Assessment of Cancer Therapy
      General (FACT-G) (quality of life), Functional Assessment of Chronic Illness
      Therapy-Fatigue (FACIT-Fatigue) (fatigue), and Pittsburgh Sleep Quality Index
      (PSQI) (sleep). We conducted descriptive statistics and responder analyses.
      RESULTS: Of 21 patients, 18 (86%) successfully completed the study. An average of
      2.8 subjects were enrolled per month. Mean scores on the PHQ-9 improved overall
      by 6.4 points (95% confidence interval [CI] 3.6-9.2). Additionally, mean FACT-G,
      FACIT-Fatigue, and PSQI scores improved in both study arms. CONCLUSION:
      Conducting antidepressant clinical trials is challenging in the oncology
      population. We approached but did not meet our feasibility goals. Depression and
      quality of life (QOL) scores improved with both mirtazapine and citalopram, but
      evidence-based pharmacologic treatments for depression in cancer patients are
      needed.

PMID- 24432821
TI  - Let our voices be heard: Urban minority adolescents share their perspectives
      regarding substance abuse and HIV/AIDS prevention messages.
AB  - PURPOSE: This study explored the substance abuse and human immunodeficiency virus
      prevention needs of urban minority adolescents. DESIGN: Six 1-hour focus groups.
      SETTING: Two high schools and two community-based organizations located in the
      city of Paterson, New Jersey. PARTICIPANTS: The sample included 41 African
      American and Latino youth, ranging in ages from 13 to 18 years. METHOD: Data were
      collected through six focus group interviews. Each group discussion was audio
      recorded and transcribed. Qualitative software was then used to facilitate the
      processes of thematic analysis, until emergent themes transcended the data. To
      bolster the rigor and confirmability of analysis, additional researchers coded
      stratified selections of transcript. RESULTS: Study participants were able to
      identify the environmental threats and structural deficits impacting their city.
      Few of the youth were able to recognize substance abuse and HIV/AIDS prevention
      messages in their immediate surroundings. Additionally, most participants
      indicated that prevention messages must be delivered in authentic ways from
      relatable sources in order to resonate with their audience. CONCLUSION: Our
      findings emphasize the importance of infusing the adolescents' voices into the
      design and implementation of health promotion messages, which could serve to
      increase their receptivity and responsiveness, and the overall resonance of the
      interventions.

PMID- 24432820
TI  - The production of nitrous oxide by the heme/nonheme diiron center of engineered
      myoglobins (Fe(B)Mbs) proceeds through a trans-iron-nitrosyl dimer.
AB  - Denitrifying NO reductases are transmembrane protein complexes that are
      evolutionarily related to heme/copper terminal oxidases. They utilize a
      heme/nonheme diiron center to reduce two NO molecules to N2O. Engineering a
      nonheme Fe(B) site within the heme distal pocket of sperm whale myoglobin has
      offered well-defined diiron clusters for the investigation of the mechanism of NO
      reduction in these unique active sites. In this study, we use FTIR spectroscopy
      to monitor the production of N2O in solution and to show that the presence of a
      distal Fe(B)(II) is not sufficient to produce the expected product. However, the
      addition of a glutamate side chain peripheral to the diiron site allows for 50%
      of a productive single-turnover reaction. Unproductive reactions are
      characterized by resonance Raman spectroscopy as dinitrosyl complexes, where one
      NO molecule is bound to the heme iron to form a five-coordinate low-spin
      {FeNO}(7) species with nu(FeNO)(heme) and nu(NO)(heme) at 522 and 1660 cm(-1),
      and a second NO molecule is bound to the nonheme Fe(B) site with a nu(NO)(FeB) at
      1755 cm(-1). Stopped-flow UV-vis absorption coupled with rapid-freeze-quench
      resonance Raman spectroscopy provide a detailed map of the reaction coordinates
      leading to the unproductive iron-nitrosyl dimer. Unexpectedly, NO binding to
      Fe(B) is kinetically favored and occurs prior to the binding of a second NO to
      the heme iron, leading to a (six-coordinate low-spin heme-nitrosyl/FeB-nitrosyl)
      transient dinitrosyl complex with characteristic nu(FeNO)(heme) at 570 +/- 2 cm(
      1) and nu(NO)(FeB) at 1755 cm(-1). Without the addition of a peripheral
      glutamate, the dinitrosyl complex is converted to a dead-end product after the
      dissociation of the proximal histidine of the heme iron, but the added peripheral
      glutamate side chain in Fe(B)Mb2 lowers the rate of dissociation of the promixal
      histidine which in turn allows the (six-coordinate low-spin heme-nitrosyl/Fe(B)
      nitrosyl) transient dinitrosyl complex to decay with production of N2O at a rate
      of 0.7 s(-1) at 4  degrees C. Taken together, our results support the proposed
      trans mechanism of NO reduction in NORs.

PMID- 24432822
TI  - Nonresident African-American fathers' influence on sons' exercise intentions in
      the fathers and sons program.
AB  - PURPOSE: To test the effects of a family-centered intervention for enhancing
      intentions to exercise among African-American boys with nonresident fathers.
      DESIGN: Quasi-experimental, intervention study. SETTING: Two Midwestern cities.
      SUBJECTS: A total of 287 nonresident African-American fathers and their 8- to 12
      year-old sons (n = 158 intervention dyads; n = 129 comparison dyads).
      INTERVENTION: The Fathers and Sons Program is a 15-session family-based
      intervention focused on promoting the health of African-American boys by
      enhancing the parenting attitudes and behaviors of their nonresident fathers and
      positively influencing parent-child interactions. MEASURES: Demographic
      information and intervention outcomes were assessed at baseline and follow-up via
      self-report. ANALYSIS: Descriptive statistics, logistic regression, and
      structural equation modeling. RESULTS: The intervention was successful in
      improving the exercise intentions of boys (B = .246; p = .005; B = .210; p =
      .012). The effect was not direct; increasing contact between fathers and sons (B
      = .154; p = .001), enhancing the quality of their relationship (B = .366; p <
      .001), and improving fathers' own intentions to exercise (B = .265; p = .001)
      were mediating factors. CONCLUSION: Interventions aimed at improving exercise
      intentions among African-American boys with nonresident fathers should focus on
      relational factors.

PMID- 24432823
TI  - African-American and Hispanic perceptions of HIV vaccine clinical research: a
      qualitative study.
AB  - PURPOSE: To examine perceptions of phase-I human immunodeficiency virus (HIV)
      vaccine trial participation among African-Americans and Hispanics in San
      Francisco, California. DESIGN: Qualitative, semistructured interviews. SETTING:
      San Francisco Department of Health. PARTICIPANTS: Thirty-six African-American and
      Hispanic men and women, 18 to 50 years of age, residing in the San Francisco Bay
      Area. METHOD: Purposive sampling using advertisements, community-based
      organization rosters, and snowball referrals. Thematic analysis of transcripts
      identified salient themes and patterns. RESULTS: Participants viewed
      participation in HIV research as important; however, they held that HIV was not a
      health priority given limited awareness about HIV research or beliefs that only
      infected or high-risk persons were eligible for participation. Altruism and
      personal gain, trustworthy trial staff, convenient schedules and facilities, and
      involvement of trusted community groups in recruitment were perceived to motivate
      participants. Concerns about the social consequences of participating in HIV
      research and product-related side effects were seen as discouraging
      participation. Limitations include the possibility that participants in interview
      research have more favorable views of biomedical research than those who refuse
      to participate. CONCLUSION: Historically, African-Americans and Hispanics in the
      United States have had limited participation in HIV trials. Understanding their
      perceptions of HIV biomedical research, identifying facilitators and barriers to
      participation, addressing misinformation about HIV, distorted risk perceptions,
      HIV stigma, and providing accessible opportunities to participate are imperative
      to ensure health equity and generalizability of findings.

PMID- 24432824
TI  - Local smoke-free public policies, quitline call rate, and smoking status in
      Kentucky.
AB  - PURPOSE: The study investigated the relationships among local smoke-free public
      policies, county-level quitline call rate, and adult smoking status. DESIGN: A
      retrospective cross-sectional examination of demographic characteristics, smoking
      status of Kentuckians, and data from the Kentucky Tobacco Quitline were used to
      investigate the relationship of local smoke-free ordinances or Board of Health
      regulations together with county-level quitline use rates and population-level
      adult smoking status. SETTING: One hundred and four Kentucky counties. SUBJECTS:
      The sample was comprised of 14,184 Kentucky participants with complete
      demographic information collected from the 2009-2010 Behavioral Risk Factor
      Surveillance System (BRFSS). MEASURES: Individual-level demographics and smoking
      status from the BRFSS; county-level urban/rural status; quitline rates; and smoke
      free policy status. ANALYSIS: Given the hierarchical structure of the dataset,
      with BRFSS respondents nested within county, multilevel modeling was used to
      determine the predictors of smoking status. RESULTS: For every 1-unit increase in
      the county-level call rate the likelihood of current smoking status decreased by
      9%. Compared to those living in communities without a policy, those in
      communities with a smoke-free public policy were 18% less likely to be current
      smokers. Limitations include quitline call rate as the sole indicator of
      cessation demand, as well as the cross-sectional design. CONCLUSION: Communities
      with smoke-free policies and higher rates of quitline use have lower rates of
      adult smoking.

PMID- 24432825
TI  - Extraordinarily fast response to low-dose sertraline in a child with severe
      obsessive-compulsive disorder and high functioning serotonin transporter
      genotype.

PMID- 24432826
TI  - A combined experimental/computational study on the adsorption of organosulfur
      compounds over metal-organic frameworks from fuels.
AB  - This work investigates the adsorption of organosulfur compounds in model fuels
      over metal-organic frameworks (MOFs) using a combined experimental/computational
      approach. Adsorption isotherms of three MOFs, MIL-101(Cr), MIL-100(Fe), and Cu
      BTC, follow the Langmuir isotherm models, and Cu-BTC shows the highest adsorption
      capacity for both dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6
      DMDBT), ascribing to the highest density of adsorption sites and fairly strong
      adsorption sites on Cu-BTC. Experimental results show adsorption selectivity of
      various compounds in model fuels follows the order of quinoline (Qu) > indole
      (In) > DBT > 4,6-DMDBT > naphthalene (Nap), which is consistent with the order of
      calculated binding energies. Adsorption capacities of thiophenic compounds
      decrease significantly with the introduction of Qu, In, or water due to their
      strong competitive adsorptions over the coordinatively unsaturated Cu sites on Cu
      BTC. The binding energies of Qu, In, H2O, and DBT are calculated as -56.04, 
      41.01, -50.27, and -27.52 kJ/mol, respectively. The experimental and
      computational results together suggest that the adsorption strength of thiophenic
      compounds over Cu-BTC is dominated by the interaction of both the conjugated pi
      system (pi-M) and the lone pair of electrons on sulfur atom (sigma-M) of
      thiophenes, with the coordinatively unsaturated sites (CUS) on Cu-BTC. Alkyl
      groups on 4- and/or 6-positions of thiophenic compounds function as both eletron
      donor to increase pi-M interaction and steric inhibitor to decrease sigma-M
      interaction. MOFs with strong and highly dense CUS can be promising materials for
      ADS of fuels. 

PMID- 24432827
TI  - Ab initio molecular dynamics study of small alkali metal clusters.
AB  - In this work, the dynamics of the clusters of the type M3 with M a metal alkaline
      atom from Li to Cs have been studied. Other heteroatomic mixed clusters like
      LiNaK and one bigger cluster, Na7, have also been studied. It was found that the
      dynamics present interesting phenomena like pseudorotations and crossovers which
      could explain the differences between experimental and theoretical values of some
      electrical properties, like the electric dipole moment of alkali metal clusters. 

PMID- 24432828
TI  - Single fiber identification with nondestructive excitation-emission spectral
      cluster analysis.
AB  - Identification methods for single textile fibers are in demand for forensic
      applications, and nondestructive methods with minimal pretreatment have the
      greatest potential for utility. Excitation-emission luminescence data provide a
      three-dimensional matrix for comparison of single-fiber dyes, and these data are
      enhanced by principal component analysis and comparison of fibers using a
      statistical figure of merit. No dye extraction methods are required to sample the
      spectra from a single fiber. This approach has been applied to the analysis of
      single fibers to compare closely matched dye pairs, acid blue (AB) 25 and 41 and
      direct blue (DB) 1 and 53. In all cases, the accuracy of fiber identification was
      high and no false positive identifications were made. 

PMID- 24432837
TI  - IgG4-related Mikulicz Disease in a 76-year-old Chinese Male: A Case Report.

PMID- 24432836
TI  - Foundation-directed therapeutic development in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that
      devastates patients and their families. It is caused by expansion of the CAG
      repeat in the huntingtin gene (HTT) and characterized pathologically by the loss
      of pyramidal neurons in several cortical areas, striatal medium spiny neurons,
      and hypothalamic neurons. Clinically, a distinguishing feature of the disease is
      uncontrolled involuntary movements (chorea) accompanied by progressive cognitive
      and psychiatric impairment. Currently there are no effective disease-modifying
      treatments for HD, although antidepressant and antipsychotic medications are
      typically utilized to manage HD symptoms, in addition to the only approved drug
      for the treatment of chorea in HD, tetrabenazine (TBZ). CHDI is a not-for-profit
      organization focused solely on HD. Herein we describe our foundation-directed
      therapeutic development efforts highlighting our collaborations and internal
      programs that are in various stages of development. 

PMID- 24432838
TI  - Single-molecule studies of intrinsically disordered proteins.

PMID- 24432835
TI  - Glucocorticoid treatment at moderate doses of SIVmac251-infected rhesus macaques
      decreases the frequency of circulating CD14+CD16++ monocytes but does not alter
      the tissue virus reservoir.
AB  - Subsets of CD16-positive monocytes produce proinflammatory cytokines and expand
      during chronic infection with the human immunodeficiency virus type 1 (HIV). HIV
      infected macrophage in tissues may be long lived and contribute to the
      establishment and maintenance of the HIV reservoir. We found that the
      (intermediate) CD14(++)CD16(+) and (nonclassical) CD14(+)CD16(++) monocyte
      subsets are significantly expanded during infection of Rhesus macaques with
      pathogenic SIV(mac251) but not during infection of sooty mangabeys with the
      nonpathogenic isolate SIVSM. In vitro glucocorticoid (GC) treatment of peripheral
      blood mononuclear cells (PBMCs) from uninfected or SIV(mac251)-infected Rhesus
      macaques and HIV-infected patients treated or not with antiretroviral therapy
      (ART) resulted in a significant decrease in the frequency of both CD16-positive
      monocyte subsets. Short-term in vivo treatment with high doses of GC of
      chronically SIV(mac251)-infected macaques resulted in a significant decrease in
      the CD14(+)CD16(++) population and, to a lesser extent, in the CD14(++)CD16(+)
      monocytes, as well as a significant decrease in the number of macrophages in
      tissues. Surprisingly, treatment of SIV(mac251)-infected macaques with ART
      significantly increased the CD14(++)CD16(+) population and the addition of GC
      resulted in a significant decrease in only the CD14(+)CD16(++) subset. No
      difference in SIV DNA levels in blood, lymph nodes, gut, and spleen was found
      between the groups treated with ART or ART plus GC. Thus, it appears that high
      doses of GC treatment in the absence of ART could affect both CD16-positive
      populations in vivo. Whether the efficacy of this treatment at higher doses to
      decrease virus levels outweighs its risks remains to be determined.

PMID- 24432839
TI  - On the catalytic hydrodefluorination of fluoroaromatics using nickel complexes:
      the true role of the phosphine.
AB  - Homogeneous catalytic hydrodefluorination (HDF) of fluoroaromatics under thermal
      conditions was achieved using nickel(0) compounds of the type [(dippe)Ni(eta(2)
      C6F6-nHn)] where n = 0-2, as the catalytic precursors. These complexes were
      prepared in situ by reacting the compound [(dippe)Ni(MU-H)]2 with the respective
      fluoroaromatic substrate. HDF seems to occur homogeneously, as tested by mercury
      drop experiments, producing the hydrodefluorinated products. However, despite
      previous findings by other groups, we found that these HDF reactions were
      actually the result of direct reaction of the alkylphosphine with the
      fluoroaromatic substrate. This metal- and silane-free system is the first
      reported example of a phosphine being able to hydrodefluorinate on its own. 

PMID- 24432840
TI  - New centrally acting agents for appetite control: from biological mechanisms to
      clinical efficacy.
AB  - BACKGROUND: Obesity is one of the major problems of health policy in different
      countries. Pharmacological attempts have been made to help affected people
      without a definitive solution. Some agents--either with peripheral or central
      effect--are available in the market. On July 2012, the FDA approved two novel
      preparations for obese patients: (1) topiramate-phentermine--the first one an
      anticonvulsant and the second one a sympathomimetic amine--and (2) lorcaserin, a
      5-HT2CR agonist. Both preparations emerged as new options for weight management.
      SCOPE: Based on the complex biology of eating behavior, in this review we discuss
      the features, mechanisms of action, pharmacokinetics, advantages and possible
      disadvantages of these new agents. CONCLUSION: With differences in efficacy
      (higher for the topiramate-phentermine combination), both preparations are active
      in reducing appetite and body weight, as well as in improving comorbidities.
      Additional information will be collected from Phase IV surveillance. Focus on
      cardiovascular, neuropsychiatric (for both introductions) and embrio-fetal safety
      (especially for topiramate) is expected.

PMID- 24432843
TI  - Computational study of the effect of dispersion interactions on the
      thermochemistry of aggregation of fused polycyclic aromatic hydrocarbons as model
      asphaltene compounds in solution.
AB  - Density functional theory (DFT), Moller-Plesset second-order perturbation theory
      (MP2), and semiempirical methods are employed for the geometry optimization and
      thermochemistry analysis of pi-pi stacked di-, tri-, tetra-, and pentamer
      aggregates of the fused polycyclic aromatic hydrocarbons (PAHs) naphthalene,
      anthracene, phenanthrene, tetracene, pyrene, and coronene as well as benzene.
      These aggregates (stabilized by dispersion interactions) are highly relevant to
      the intermolecular aggregation of asphaltenes, major components of heavy
      petroleum. The strength of pi-pi stacking interaction is evaluated with respect
      to the pi-stacking distance and thermochemistry results, such as aggregation
      enthalpies, entropies, and Gibbs free energies (DeltaG(298)). For both pi
      stacking interplanar distances and thermochemistry, the omegaB97X-D functional
      with an augmented damped R(-6) dispersion correction term and MP2 are in the
      closest agreement with the highly accurate spin-component scaled MP2 (SCS-MP2)
      method that we selected as a reference. The DeltaG(298) values indicate that the
      aggregation of coronene is spontaneous at 298 K and the formation of pyrene
      dimers occurs spontaneously at temperature lower than 250 K. Aggregates of
      smaller PAHs would be stable at even lower temperature. These findings are
      supported by X-ray crystallographic determination results showing that among the
      PAHs studied only coronene forms continuous stacked aggregates in single
      crystals, pyrene forms dimers, and smaller PAHs do not form pi-pi stacked
      aggregates. Thermochemistry analysis results show that PAHs containing more than
      four fused benzene rings would spontaneously form aggregates at 298 K. Also,
      round-shaped PAHs, such as phenanthrene and pyrene, form more stable aggregates
      than linear PAHs, such as anthracene and tetracene, due to decreased entropic
      penalty. These results are intended to help guide the synthesis of model
      asphaltene compounds for spectroscopic studies so as to help understand the
      aggregation behavior of heavy petroleum. 

PMID- 24432844
TI  - Precision treatment for cancer: role of prognostic and predictive markers.
AB  - Precision or personalized treatment can be defined as using the biological
      characteristics of a patient's disease in order to administer the most effective
      therapy at the optimum dose. The aim of this article is to discuss the use of
      prognostic and predictive markers to aid precision treatment in patients with
      cancer. Prognostic markers help to differentiate between indolent and life
      threatening disease and thereby identify who should or should not receive
      adjuvant systemic therapy following surgical removal of a primary tumor.
      Predictive markers, on the other hand, help to identify upfront those patients
      who are likely to be responsive or resistant to a specific therapy. The use of
      prognostic and predictive markers can thus help to match each patient to the most
      effective and least toxic therapy and as a result avoid preventable toxicity and
      unnecessary costs.

PMID- 24432845
TI  - FOXN1 in organ development and human diseases.
AB  - FOXN1 gene belongs to the forkhead box gene family that comprises a diverse group
      of "winged-helix" transcription factors that have been implicated in a variety of
      biochemical and cellular processes, such as development, metabolism, aging and
      cancer. These transcription factors share the common property of being
      developmentally regulated and of directing tissue-specific transcription and cell
      fate decisions. Foxn1 is selectively expressed in thymic and skin epithelial
      cells, where it acts through its molecular targets to regulate the balance
      between growth and differentiation. In particular, Foxn1 is required for thymic
      epithelial patterning and differentiation from the initial epithelial thymic
      anlage to a functional cortical and medullary thymic epithelial cells (TECs)
      meshwork necessary for the crosstalk with the lymphoid compartment. A mutation in
      FoxN1 generates alymphoid cystic thymic dysgenesis due to defective TECs, causing
      primary T-cell immunodeficiency, named Nude/SCID syndrome, and leads to a
      hairless "nude" phenotype in both mice and humans. This immune defect represents
      the first example of a Severe Combined Immunodeficiencies (SCID) phenotype not
      primarily related to an abnormality intrinsic of the hematopoietic cell, but
      rather to a peculiar alteration of the thymic epithelia cell. This review focuses
      on the key role of FOXN1 in cell development and its clinical implication in
      humans. 

PMID- 24432852
TI  - Filling dynamics of closed end nanocapillaries.
AB  - We have studied the filling dynamics of model capillaries using dynamic mean
      field theory for a confined lattice gas and Kawasaki dynamics simulations. We
      have found two different scenarios for filling of capped nanocapillaries from the
      vapor phase. As compared to channels with macroscopic width, in which the filling
      process occurs by the detachment of the meniscus from the cap, in mesoscopic
      channels there is an alternative mechanism associated with the spontaneous
      condensation of the liquid close to the pore opening and its subsequent growth
      toward the closed pore end. We show that these two scenarios have totally
      different filling dynamics, providing an additional mechanism for slow capillary
      condensation kinetics in nanoscopic objects. 

PMID- 24432853
TI  - Single-file nanochannel persistence lengths from NMR.
AB  - Crystalline solids composed of one-dimensional channels with cross-sectional
      dimensions below 1 nm represent an intriguing class of materials with important
      potential applications. A key characteristic for certain applications is the
      average open channel persistence length, i.e., the ensemble average distance from
      a channel opening to the first obstruction. This paper introduces an NMR-based
      methodology to measure this quantity. The protocol is applied to polycrystalline
      specimens of two different dipeptide nanotubes: l-Ala-l-Val and its retro-analog
      l-Val-l-Ala. Persistence lengths derived from the NMR measurements are found to
      be comparable to the typical crystallite dimensions seen in scanning electron
      microscopy (SEM) images, indicating that the crystals of these AV and VA
      specimens are essentially hollow with practically no blockages. Applications of
      the method to an AV sample that has been pulverized in a mortar and pestle showed
      that the open channel persistence length was reduced from 50 to 6.6 MUm,
      consistent with the crystallite sizes observed in SEM images. 

PMID- 24432854
TI  - Biomarkers, behavior, and intellectual and developmental disabilities.

PMID- 24432855
TI  - A psychophysiology of developmental disabilities: a personal and historical
      perspective.

PMID- 24432856
TI  - A multimethod assessment of anxiety and problem behavior in children with autism
      spectrum disorders and intellectual disability.
AB  - Despite the increased risk for anxiety disorders in children with autism spectrum
      disorders (ASD), there is a lack of research on the assessment and treatment of
      anxiety in this population, particularly for those with an intellectual
      disability (ID). The present study evaluated a multimethod strategy for the
      assessment of anxiety and problem behavior in three children with ASD and ID.
      Anxiety was operationally defined using: (1) behavioral data from anxious
      behaviors, (2) affective/contextual data from parent-report and observer ratings
      of overall anxiety, and (3) physiological data (heart rate [HR] and respiratory
      sinus arrhythmia [RSA]). A functional assessment of problem behavior during high-
      and low-anxiety conditions was conducted. Higher levels of problem behavior and
      HR and lower RSA were found in the high-anxiety than in the low-anxiety
      conditions.

PMID- 24432857
TI  - Sequential analysis of autonomic arousal and self-injurious behavior.
AB  - There have been limited direct tests of the hypothesis that self-injurious
      behavior (SIB) regulates arousal. In this study, two autonomic biomarkers for
      physiological arousal (heart rate [HR] and the high-frequency [HF] component of
      heart rate variability [HRV]) were investigated in relation to SIB for 3
      participants with intellectual disabilities. Second-by-second correlations were
      examined using time series statistical models. The probabilities of HR changes
      preceding or following SIB were derived using sequential analyses and compared
      using resampling procedures. Significant correlations and sequential dependencies
      were found between SIB and arousal parameters. Combining within-subject
      statistical methods with single-subject experimental designs may provide a
      replicable methodology for use across larger samples to examine relationships
      between SIB and arousal in real-world settings.

PMID- 24432858
TI  - Biobehavioral indicators of social fear in young children with fragile X
      syndrome.
AB  - Anxiety is among the most impairing conditions associated with Fragile X syndrome
      (FXS) and is putatively linked to atypical physiological arousal. However, few
      studies have examined this association in young children with FXS. The authors
      examined whether patterns of arousal and behavior during an experimental stranger
      approach paradigm differ between a cross-sectional sample of 21 young children
      with FXS and 19 controls (12-58 months old). Groups did not differ in mean levels
      of behavioral fear. Unlike the control group, however, the FXS group demonstrated
      increased facial fear at older ages, as well as age-dependent changes in
      associations between heart activity and distress vocalizations. These findings
      may inform theoretical models of anxiety etiology in FXS and early detection
      efforts.

PMID- 24432859
TI  - Examining the relationship between heart rate and problem behavior: a case study
      of severe skin picking in Prader-Willi syndrome.
AB  - Few studies have examined the relationship between heart rate and self-injurious
      behavior (SIB) shown by individuals with IDD (intellectual and developmental
      disabilities). In this single-case study, we simultaneously monitored heart rate
      and activity levels during a functional analysis of severe skin picking behavior
      exhibited by a young man with Prader-Willi syndrome (PWS). Results of the
      functional analysis indicated that the participant's skin picking was maintained
      by automatic reinforcement. A within-session analysis of the data indicated that
      skin picking bouts resulted in an increase in heart rate, suggesting a positive-
      automatic reinforcement function. These data indicate that inclusion of heart
      rate and activity-level monitoring during a functional analysis may provide
      important additional information concerning the determinants of SIB.

PMID- 24432868
TI  - Coexisting chronic conditions associated with mortality and morbidity in adult
      patients with asthma.
AB  - OBJECTIVE: Many asthma patients suffer from chronic conditions other than asthma.
      We investigated the specific contribution of common comorbidities on mortality
      and morbidity in adult asthma. METHODS: In an observational study of adults with
      incident asthma identified between 1999 and 2003 using National Veterans Affairs
      and Centers for Medicare and Medicaid Services encounter databases (n = 25 975,
      follow-up 3.0 +/- 1.7 years), association between 13 most prevalent comorbidities
      (hypertension, ischemic heart disease (IHD), osteoarthritis, rheumatoid
      arthritis, diabetes, mental disorders, substance/drug abuse, enlarged prostate,
      depression, cancer, alcoholism, HIV and heart failure) and four conditions
      previously associated with asthma (sleep apnea, gastroesophageal reflux disease
      (GERD), rhinitis and sinusitis) and mortality, hospitalizations and asthma
      exacerbations were assessed using multivariate regression analyses adjusted for
      other clinically important covariates. RESULTS: HIV followed by alcoholism and
      mental disorders among 18-45-years old, and heart failure, diabetes, IHD and
      cancer among those >= 65 years old were associated with an increased risk of all
      cause mortality. Many conditions were associated with increased risk for all
      cause hospitalizations, but the increased risk was consistent across all ages for
      mental disorders. For asthma exacerbations, mental disorder followed by substance
      abuse and IHD were associated with increased risk among those 18-45 years old,
      and chronic sinusitis, mental disorder and IHD among those >= 65-years old. GERD
      was associated with decreased risk for asthma exacerbation in all ages.
      CONCLUSIONS: Many comorbidities are associated with poor outcome in adult
      asthmatics and their effect differs by age. Mental disorders are associated with
      increased risk of mortality and morbidity across ages.

PMID- 24432869
TI  - Asthma characteristics among older adults: using the California health interview
      survey to examine asthma incidence, morbidity and ethnic differences.
AB  - OBJECTIVE: The purpose of this study was to examine the incidence,
      characteristics of asthma morbidity and care, and ethnic differences that exist
      in older adults with asthma in California. METHODS: Data were from the 2009
      California Health Interview Survey (CHIS). Characteristics of older adults (>=65
      years) with and without asthma were compared using population-weighted estimates.
      Asthma-specific variables were compared among different ethnic groups.
      Multivariate analyses were preformed to determine factors associated with asthma
      status, asthma episodes/attacks, asthma symptom frequency and emergency
      department (ED) visits due to asthma. RESULTS: Asthma was present in 8.1% of
      older adults, among which, 67.3% reported taking medication daily for asthma.
      Asthma symptoms were experienced every day by almost 20%, with over 34% of
      seniors with asthma having symptoms at least once per week. Despite having a
      lower frequency of asthma symptoms, Hispanics were 5.31 times more likely to
      visit the ED due to asthma than were Caucasians. CONCLUSIONS: The findings from
      the study showed that older adults with asthma had difficulty with asthma
      control. We recommend a focus on asthma education so that when symptoms do occur,
      options are available to avoid costly ED visits. Further research should focus on
      specific asthma management skills and adherence to asthma treatment regimen among
      ethnic groups.

PMID- 24432860
TI  - Physiological arousal in autism and fragile X syndrome: group comparisons and
      links with pragmatic language.
AB  - This study tested the hypothesis that pragmatic (i.e., social) language
      impairment is linked to arousal dysregulation in autism spectrum disorder (ASD)
      and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 27 with
      typical development (TD), aged 4-15 years, participated. Boys with FXS were
      hyperaroused compared to boys with TD but did not differ from boys with ASD.
      Dampened vagal tone predicted pragmatic impairment in ASD, and associations
      emerged between cardiac activity and receptive/expressive vocabulary across
      groups. Findings support autonomic dysfunction as a mechanism underlying
      pragmatic impairment in ASD and suggest that biophysiological profiles are shared
      in ASD and FXS, which has implications for understanding the role of fragile X
      mental retardation-1 (FMR1, the FXS gene) in the pathophysiology of ASD.

PMID- 24432870
TI  - Back pocket flexibility provides group II p21-activated kinase (PAK) selectivity
      for type I 1/2 kinase inhibitors.
AB  - Structure-based methods were used to design a potent and highly selective group
      II p21-activated kinase (PAK) inhibitor with a novel binding mode, compound 17.
      Hydrophobic interactions within a lipophilic pocket past the methionine
      gatekeeper of group II PAKs approached by these type I 1/2 binders were found to
      be important for improving potency. A structure-based hypothesis and strategy for
      achieving selectivity over group I PAKs, and the broad kinome, based on unique
      flexibility of this lipophilic pocket, is presented. A concentration-dependent
      decrease in tumor cell migration and invasion in two triple-negative breast
      cancer cell lines was observed with compound 17. 

PMID- 24432871
TI  - Smart detection of toxic metal ions, Pb2+ and Cd2+, using a 129Xe NMR-based
      sensor.
AB  - An approach for sensitive magnetic resonance detection of metal cations is
      proposed. Combining the use of hyperpolarized (129)Xe NMR and of a cage-molecule
      functionalized by a ligand able to chelate different cations, we show that
      simultaneous detection of lead, zinc, and cadmium ions at nanomolar concentration
      is possible in short time, thanks to fast MRI sequences based on the HyperCEST
      scheme. 

PMID- 24432872
TI  - Reduction in the length of stay with rivaroxaban as a single-drug regimen for the
      treatment of deep vein thrombosis and pulmonary embolism.
AB  - OBJECTIVE: The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the
      potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and
      pulmonary embolism (PE). The length of initial hospitalization in patients
      presenting with either symptomatic DVT or PE was assessed using hospitalization
      records from these trials. METHODS: Analyses were carried out in the intention-to
      treat population, using non-parametric and parametric statistical methods.
      RESULTS: Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of
      EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized
      patients with a length of stay of five or fewer days receiving rivaroxaban was
      54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with
      DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6
      10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of
      enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were
      39% and 46% in the rivaroxaban and enoxaparin/VKA groups, respectively. Overall,
      length of stay was significantly shorter in the rivaroxaban group, compared with
      the enoxaparin/VKA group across all analyses performed (p < 0.0001). Across
      regions, the observed admission rates and length of stay duration varied greatly:
      Asia had the longest overall hospitalization rates, whereas the lowest rates were
      reported in North America, Australia and New Zealand. Nevertheless, a consistent
      trend was observed: length of hospital stay in patients with DVT or PE receiving
      rivaroxaban was shorter than, or at least similar to, patients receiving
      enoxaparin/VKA. CONCLUSION: A single-drug regimen with rivaroxaban may reduce the
      burden on healthcare systems and patients, and provides effective and well
      tolerated treatment. The studies shared an open-label design that allowed
      comparison of initial hospitalization, but limitations include the well monitored
      clinical trial setting in which decisions on admission and discharge could vary
      from real-world management.

PMID- 24432873
TI  - High-performance organic thin-film transistors of J-stacked squaraine dyes.
AB  - We have synthesized a series of dipolar squaraine dyes that contain dicyanovinyl
      groups as acceptor and benzannulated five-membered ring heterocycles with alkyl
      chains of varied length as donor moieties. Based on these squaraines, thin-film
      transistors (TFT) were fabricated by spin coating and solution shearing.
      Moreover, with one of these squaraine derivatives vacuum-deposited TFTs were
      prepared as well. Our detailed studies revealed that the transistor performance
      of the present series of squaraines is strongly dependent on their structural
      features as well as on the processing method of thin films. Thus, solution
      sheared OTFTs of selenium squaraine bearing dodecyl substituents (denoted as Se
      SQ-C12) performed best with a maximum hole mobility of 0.45 cm(2) V(-1) s(-1),
      which is by far the highest value yet reported for OTFTs based on squaraines.
      This value was even surpassed by vacuum-deposited thin films of n-butyl
      substituted selenium squaraine Se-SQ-C4, the only sublimable compound in this
      series, exhibiting a record hole mobility of 1.3 cm(2) V(-1) s(-1). Furthermore,
      we have investigated the morphology of the thin films and the molecular packing
      of these squaraine dyes by optical spectroscopy, atomic force microscopy, and X
      ray diffraction. These studies revealed a relationship between the molecular
      structure, packing motif, thin-film morphology, and transistor performance of the
      squaraine dyes. From the supramolecular point of view two packing features
      discovered in the single crystal structure of Se-SQ-C8 are of particular interest
      with regard to the structure-functionality relationship: The first is the slipped
      and antiparallel pi-stacking motif which ensures cancellation of the molecules'
      dipole moments and J-type absorption band formation in thin films. The second is
      the presence of CN...Se noncovalent bonds which show similarities to the more
      common halogen-bonding interactions and which interconnect the individual one
      dimensional slipped pi-stacks, thus leading to two-dimensional percolation
      pathways along the source-drain direction. 

PMID- 24432874
TI  - News media framing of serious mental illness and gun violence in the United
      States, 1997-2012.
AB  - Recent mass shootings by persons seemingly afflicted with serious mental illness
      (SMI) have received extensive news media coverage and prompted national dialogue
      about the causes of, and policy responses to, mass shootings. News media framing
      of SMI as a cause of gun violence may influence public attitudes about persons
      with SMI and support for gun violence prevention proposals. We analyzed the
      content of a 25% random sample of news stories on SMI and gun violence published
      in 14 national and regional news sources from 1997 to 2012. Across the study
      period, most news coverage occurred in the wake of mass shootings, and "dangerous
      people" with SMI were more likely than "dangerous weapons" to be mentioned as a
      cause of gun violence. 

PMID- 24432875
TI  - Sodium intake in a cross-sectional, representative sample of New York City
      adults.
AB  - OBJECTIVES: We estimated sodium intake, which is associated with elevated blood
      pressure, a major risk factor for cardiovascular disease, and assessed its
      association with related variables among New York City adults. METHODS: In 2010
      we conducted a cross-sectional, population-based survey of 1656 adults, the Heart
      Follow-Up Study, that collected self-reported health information, measured blood
      pressure, and obtained sodium, potassium, and creatinine values from 24-hour
      urine collections. RESULTS: Mean daily sodium intake was 3239 milligrams per day;
      81% of participants exceeded their recommended limit. Sodium intake was higher in
      non-Hispanic Blacks (3477 mg/d) and Hispanics (3395 mg/d) than in non-Hispanic
      Whites (3066 mg/d; both P < .05). Higher sodium intake was associated with higher
      blood pressure in adjusted models, and this association varied by race/ethnicity.
      CONCLUSIONS: Higher sodium intake among non-Hispanic Blacks and Hispanics than
      among Whites was not previously documented in population surveys relying on self
      report. These results demonstrate the feasibility of 24-hour urine collection for
      the purposes of research, surveillance, and program evaluation.

PMID- 24432876
TI  - Diet-beverage consumption and caloric intake among US adults, overall and by body
      weight.
AB  - OBJECTIVES: We examined national patterns in adult diet-beverage consumption and
      caloric intake by body-weight status. METHODS: We analyzed 24-hour dietary recall
      with National Health and Nutrition Examination Survey 1999-2010 data (adults aged
      >= 20 years; n = 23 965). RESULTS: Overall, 11% of healthy-weight, 19% of
      overweight, and 22% of obese adults drink diet beverages. Total caloric intake
      was higher among adults consuming sugar-sweetened beverages (SSBs) compared with
      diet beverages (2351 kcal/day vs 2203 kcal/day; P = .005). However, the
      difference was only significant for healthy-weight adults (2302 kcal/day vs 2095
      kcal/day; P < .001). Among overweight and obese adults, calories from solid-food
      consumption were higher among adults consuming diet beverages compared with SSBs
      (overweight: 1965 kcal/day vs 1874 kcal/day; P = .03; obese: 2058 kcal/day vs
      1897 kcal/day; P < .001). The net increase in daily solid-food consumption
      associated with diet-beverage consumption was 88 kilocalories for overweight and
      194 kilocalories for obese adults. CONCLUSIONS: Overweight and obese adults drink
      more diet beverages than healthy-weight adults and consume significantly more
      solid-food calories and a comparable total calories than overweight and obese
      adults who drink SSBs. Heavier US adults who drink diet beverages will need to
      reduce solid-food calorie consumption to lose weight.

PMID- 24432877
TI  - Preparedness for natural disasters among older US adults: a nationwide survey.
AB  - OBJECTIVES: We sought to determine natural disaster preparedness levels among
      older US adults and assess factors that may adversely affect health and safety
      during such incidents. METHODS: We sampled adults aged 50 years or older (n =
      1304) from the 2010 interview survey of the Health and Retirement Study. The
      survey gathered data on general demographic characteristics, disability status or
      functional limitations, and preparedness-related factors and behaviors. We
      calculated a general disaster preparedness score by using individual indicators
      to assess overall preparedness. RESULTS: Participant (n = 1304) mean age was 70
      years (SD = 9.3). Only 34.3% reported participating in an educational program or
      reading materials about disaster preparation. Nearly 15% reported using
      electrically powered medical devices that might be at risk in a power outage. The
      preparedness score indicated that increasing age, physical disability, and lower
      educational attainment and income were independently and significantly associated
      with worse overall preparedness. CONCLUSIONS: Despite both greater vulnerability
      to disasters and continuous growth in the number of older US adults, many of the
      substantial problems discovered are remediable and require attention in the
      clinical, public health, and emergency management sectors of society.

PMID- 24432878
TI  - Gender disparities in HIV treatment outcomes following release from jail: results
      from a multicenter study.
AB  - OBJECTIVES: We assessed gender differences in longitudinal HIV treatment outcomes
      among HIV-infected jail detainees transitioning to the community. METHODS: Data
      were from the largest multisite prospective cohort study of HIV-infected released
      jail detainees (n = 1270)-the Enhancing Linkages to HIV Primary Care and Services
      in Jail Setting Initiative, January 2008 and March 2011, which had 10 sites in 9
      states. We assessed baseline and 6-month HIV treatment outcomes, stratifying by
      gender. RESULTS: Of 867 evaluable participants, 277 (31.9%) were women. Compared
      with men, women were more likely to be younger, non-Hispanic White, married,
      homeless, and depressed, but were similar in recent alcohol and heroin use. By 6
      months postrelease, women were significantly less likely than men to experience
      optimal HIV treatment outcomes, including (1) retention in care (50% vs 63%), (2)
      antiretroviral therapy prescription (39% vs 58%) or optimal antiretroviral
      therapy adherence (28% vs 44%), and (3) viral suppression (18% vs 30%). In
      multiple logistic regression models, women were half as likely as men to achieve
      viral suppression. CONCLUSIONS: HIV-infected women transitioning from jail
      experience greater comorbidity and worse HIV treatment outcomes than men. Future
      interventions that transition people from jail to community-based HIV clinical
      care should be gender-specific.

PMID- 24432879
TI  - A heavy burden: the cardiovascular health consequences of having a family member
      incarcerated.
AB  - OBJECTIVES: We examined the association of family member incarceration with
      cardiovascular risk factors and disease by gender. METHODS: We used a sample of
      5470 adults aged 18 years and older in the National Survey of American Life, a
      2001-2003 nationally representative cross-sectional survey of Blacks and Whites
      living in the United States, to examine 5 self-reported health conditions
      (diabetes, hypertension, heart attack or stroke, obesity, and fair or poor
      health). RESULTS: Family member incarceration was associated with increased
      likelihood of poor health across all 5 conditions for women but not for men. In
      adjusted models, women with family members who were currently incarcerated had
      1.44 (95% confidence interval [CI] = 1.03, 2.00), 2.53 (95% CI = 1.80, 3.55), and
      1.93 (95% CI = 1.45, 2.58) times the odds of being obese, having had a heart
      attack or stroke, and being in fair or poor health, respectively. CONCLUSIONS:
      Family member incarceration has profound implications for women's cardiovascular
      health and should be considered a unique risk factor that contributes to racial
      disparities in health.

PMID- 24432880
TI  - Impact of Alabama's immigration law on access to health care among Latina
      immigrants and children: implications for national reform.
AB  - We conducted in-depth interviews in May to July 2012 to evaluate the effect of
      Alabama's 2011 omnibus immigration law on Latina immigrants and their US- and
      foreign-born children's access to and use of health services. The predominant
      effect of the law on access was a reduction in service availability.
      Affordability and acceptability of care were adversely affected because of
      economic insecurity and women's increased sense of discrimination. Nonpregnant
      women and foreign-born children experienced the greatest barriers, but pregnant
      women and mothers of US-born children also had concerns about accessing care. The
      implications of restricting access to health services and the potential impact
      this has on public health should be considered in local and national immigration
      reform discussions. 

PMID- 24432881
TI  - Medicaid policies and practices in US state prison systems.
AB  - Medicaid is an important source of health care coverage for prison-involved
      populations. From 2011 to 2012, we surveyed state prison system (SPS) policies
      affecting Medicaid enrollment during incarceration and upon release; 42 of 50
      SPSs participated. Upon incarceration, Medicaid benefits were suspended in 9
      (21.4%) SPSs and terminated in 28 (66.7%); 27 (64.3%) SPSs screened prisoners for
      potential Medicaid eligibility. Although many states supported Medicaid
      enrollment upon release, several did not. We have considered implications for
      Medicaid expansion. 

PMID- 24432882
TI  - Underreporting work absences for nontraumatic work-related musculoskeletal
      disorders to workers' compensation: results of a 2007-2008 survey of the Quebec
      working population.
AB  - OBJECTIVES: We examined underestimation of nontraumatic work-related
      musculoskeletal disorders (WMSDs) stemming from underreporting to workers'
      compensation (WC). METHODS: In data from the 2007 to 2008 Quebec Survey on
      Working and Employment Conditions and Occupational Health and Safety we
      estimated, among nonmanagement salaried employees (NMSEs) (1) the prevalence of
      WMSDs and resulting work absence, (2) the proportion with WMSD-associated work
      absence who filed a WC claim, and (3) among those who did not file a claim, the
      proportion who received no replacement income. We modeled factors associated with
      not filing with multivariate logistic regression. RESULTS: Eighteen percent of
      NMSEs reported a WMSD, among whom 22.3% were absent from work. More than 80% of
      those absent did not file a WC claim, and 31.4% had no replacement income.
      Factors associated with not filing were higher personal income, higher seniority,
      shorter work absence, and not being unionized. CONCLUSIONS: The high level of
      WMSD underreporting highlights the limits of WC data for surveillance and
      prevention. Without WC benefits, injured workers may have reduced job protection
      and access to rehabilitation.

PMID- 24432883
TI  - Previous exposure to HCV among persons born during 1945-1965: prevalence and
      predictors, United States, 1999-2008.
AB  - OBJECTIVES: We examined HCV exposure prevalence and predictors among persons in
      the United States born during 1945-1965. METHODS: With data from the 1999-2008
      National Health and Nutrition Examination Survey, we calculated the proportion of
      persons born during 1945-1965 who tested positive for HCV antibody (anti-HCV) and
      analyzed the prevalence by sociodemographic and behavioral risk factors. RESULTS:
      Anti-HCV prevalence in the 1945-1965 birth cohort was 3.2% (95% confidence
      interval [CI] = 2.8%, 3.8%), substantially higher than among other adults (0.9%).
      Within the cohort, anti-HCV prevalence was higher among non-Hispanic Blacks
      (6.4%; 95% CI = 5.3%, 7.7%), persons with injection drug use histories (56.8%;
      95% CI = 48.4%, 64.8%), and persons with elevated alanine aminotransferase levels
      (12.7%; 95% CI = 10.7%, 15.1%). Injection drug use (adjusted odds ratio = 98.4;
      95% CI = 58.8, 164.5) was the strongest anti-HCV prevalence predictor. Among anti
      HCV-positive persons, 57.8% reported having 2 or more alcoholic drinks daily.
      CONCLUSIONS: With the high prevalence of HCV among persons born during 1945-1965,
      the increasing morbidity and mortality associated with HCV, and reductions in
      liver cancer and HCV-related mortality when HCV is eradicated, it is critically
      important to identify persons with HCV and link them to appropriate care.

PMID- 24432884
TI  - Racial disparities in life expectancy in Brazil: challenges from a multiracial
      society.
AB  - OBJECTIVES: We calculated life expectancy at birth for Whites, Blacks, and mixed
      races in Brazil, and decomposed the differences by causes of death. METHODS: We
      used Ministry of Health death records and 2010 Census population data
      (190,755,799 residents and 1,136,947 deaths). We applied the Arriaga methodology
      to calculate decomposition of life expectancy by cause of death. We performed
      sensitivity analyses for underreporting of deaths, missing data, and numerator
      denominator bias. RESULTS: Using standard life table methods, female life
      expectancy was highest for mixed races (78.80 years), followed by Whites (77.54
      years), then Blacks (76.32 years). Male life expectancy was highest for Whites
      (71.10 years) followed closely by mixed races (71.08 years), and lower for Blacks
      (70.11 years). Homicides contributed the most to the relative life expectancy
      increase for Whites, and cancer decreased the gap. After adjustment for
      underreporting, missing data, and numerator-denominator bias, life expectancy was
      higher for Whites than for Blacks and mixed races. CONCLUSIONS: Despite wide
      socioeconomic differences between Whites and mixed races, standard life table
      methods showed that mixed races had higher life expectancy than Whites for women,
      and similar for men. With the increase of multiracial populations, measuring
      racial disparities in life expectancy will be a fast-growing challenge.

PMID- 24432886
TI  - Combinatorial science: taking inspiration from biology and youth.

PMID- 24432885
TI  - "A breath of fresh air worth spreading": media coverage of retailer abandonment
      of tobacco sales.
AB  - OBJECTIVES: Media play an important role in the diffusion of innovations by
      spreading knowledge of their relative advantages. We examined media coverage of
      retailers abandoning tobacco sales to explore whether this innovation might be
      further diffused by media accounts. METHODS: We searched online media databases
      (Lexis Nexis, Proquest, and Access World News) for articles published from 1995
      to 2011, coding retrieved items through a collaborative process. We analyzed the
      volume, type, provenance, prominence, and content of coverage. RESULTS: We found
      429 local and national news items. Two retailers who were the first in their
      category to end tobacco sales received the most coverage and the majority of
      prominent coverage. News items cited positive potential impacts of the decision
      more often than negative potential impacts, and frequently referred to tobacco
      caused disease, death, or addiction. Letters to the editor and editorials were
      overwhelmingly supportive. CONCLUSIONS: The content of media coverage about
      retailers ending tobacco sales could facilitate broader diffusion of this policy
      innovation, contributing to the denormalization of tobacco and moving society
      closer to ending the tobacco epidemic. Media advocacy could increase and enhance
      such coverage.

PMID- 24432887
TI  - Coronary sinus cannulation with a steerable catheter during biventricular device
      implantation.
AB  - OBJECTIVES: To determine whether a steerable catheter with electrogram guidance
      (CS-assist group) could facilitate access to the coronary sinus (CS) during
      cardiac resynchronization therapy (CRT) implantation. DESIGN: Consecutive
      patients who underwent CRT implantation were recruited prospectively into the CS
      assist group (n = 81) and compared with those using conventional techniques
      without an electrogram guidance (conventional group, n = 101). RESULTS: The CS
      cannulation success rate was clearly greater in the CS-assist group (100%) than
      that in the conventional group (95%, p < 0.05), with significantly shorter mean
      procedure time (52.6 +/- 20.6 min vs. 73.2 +/- 40.9 min, p < 0.01) and
      fluoroscopy time (3.6 +/- 3.2 min vs. 14.2 +/- 20.4 min, p < 0.01). In the five
      CS cannulation failure cases, mean procedure time (144.0 +/- 37.0 min) and
      fluoroscopy time (57.8 +/- 24.8 min) were significantly longer than those in the
      other patients (61.2 +/- 32.3 and 8.2 +/- 13.6 min, respectively, n = 177, both p
      < 0.01). CONCLUSIONS: Using the steerable catheter with real-time electrogram
      guidance, location of and access to the CS is more rapid and successful, which
      may improve the success of the CRT implantation and may give significant time
      savings.

PMID- 24432892
TI  - Two rare cases of blastic plasmacytoid dendritic cell neoplasm and a literature
      review.

PMID- 24432893
TI  - Busulfan-containing conditioning regimens are optimal preparative regimens for
      autologous stem cell transplant in patients with diffuse large B-cell lymphoma.
AB  - We retrospectively examined the outcomes of 56 patients with diffuse large B-cell
      lymphoma (DLBCL) who underwent autologous stem cell transplant (ASCT) with
      BEAM/BEAC (carmustine, etoposide, cytarabine, melphalan/cyclophosphamide) or
      busulfan (Bu)-containing conditioning regimens. The Bu group had lower disease
      related mortality and more frequent achievement of complete remission (CR) after
      ASCT from partial remission (PR) or refractory status before ASCT compared with
      the BEAM/BEAC group. The estimated 2-year EFS (59.3% vs. 15.0%) and overall
      survival (OS) (70.2% vs. 42.0%) in pre-ASCT rituximab-exposed patients with DLBCL
      were higher in the Bu group. In patients with high-risk DLBCL exposed to
      rituximab with first remission, the Bu group had better EFS (p = 0.004) and OS (p
      = 0.053) rates, while survival rates for relapsed/refractory patients did not
      differ between groups. Bu regimens are highly effective for preparing patients
      with DLBCL with previous exposure to rituximab for ASCT, especially in high-risk
      patients who achieved a first remission.

PMID- 24432894
TI  - High dose chemotherapy with autologous stem cell transplant for patients with
      transformed B-cell non-Hodgkin lymphoma in the rituximab era.
AB  - High dose chemotherapy with autologous stem cell transplant (HD-ASCT) is a
      recommended procedure for patients with transformed indolent B-cell lymphoma from
      the pre-rituximab era. In this retrospective single-center study, we present our
      experience with HD-ASCT in patients with histologically verified transformed
      indolent B-cell lymphoma in the rituximab era. Forty-two patients were included,
      of whom 28 with chemosensitive disease proceeded to HD-ASCT. Twenty patients
      (71%) achieved a complete response (CR) and five (18%) a partial response (PR)
      after HD-ASCT. With a median observation time of 49 months for the survivors, the
      median progression-free survival (PFS) and overall survival (OS) for patients
      with HD-ASCT were 39 months and 57 months, respectively. Patients who were
      rituximab-naive at transformation had a significantly better OS compared to
      patients previously treated with rituximab, both in the whole patient cohort and
      among the HD-ASCT-treated patients (p = 0.036 and p = 0.039, respectively).
      Furthermore, male sex influenced survival negatively, whereas time from diagnosis
      to transformation was positively associated with survival, both with borderline
      significance, in HD-ASCT-treated patients. In conclusion, HD-ASCT remains an
      effective treatment for transformed indolent lymphomas in the rituximab era.

PMID- 24432895
TI  - Is there a role for therapy response assessment with 2-[fluorine-18] fluoro-2
      deoxy-D-glucose-positron emission tomography/computed tomography in mantle cell
      lymphoma?
AB  - 2-[Fluorine-18] fluoro-2-deoxy-D-glucose-positron emission tomography/computed
      tomography (FDG-PET/CT) scanning is used for response assessment in mantle cell
      lymphoma (MCL). However, its ability to predict outcome is debatable. We
      retrospectively evaluated the prognostic impact of interim and post therapy FDG
      PET/CT scan on outcome of 58 consecutive MCL patients. Scans performed at
      diagnosis, mid-therapy, post-chemotherapy and post-transplant were reviewed and
      outcome analyzed. Median age was 59; MCL International Prognostic Index (MIPI)
      was low in 45%, intermediate in 41% and high in 14%. Thirty-four patients (58%)
      received R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin,
      prednisone) or R-CHOP-like chemotherapy, 24 (42%) underwent upfront autologous
      stem-cell transplant (ASCT). Three-year overall (OS) and progression-free
      survival (PFS) were 81% and 45%, respectively. No differences in OS or PFS
      between PET-positive and PET-negative groups both for interim and post-therapy
      scans were observed. We conclude that in patients treated with R-CHOP, using the
      International-Harmonization-Project criteria for FDG-PET/CT interpretation, there
      is no role for interim or post-therapy PET.

PMID- 24432896
TI  - Evolving treatment strategies in patients with high-risk acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is defined by a set of biologically distinct
      diseases characterized by maturation arrest and clonal proliferation of myeloid
      cells. Recommendations for post-remission therapy depend on assessing the
      leukemia risk characteristics, such as cytogenetics and molecular features
      present at diagnosis. Patients with high-risk disease include those whose
      leukemia is characterized by monosomal karyotype or poor-risk cytogenetic or
      molecular abnormalities, patients with antecedent hematologic disorders or
      therapy-related AML, and presence of adverse host factors, such as comorbidities,
      impaired performance status or older age. Older patients are more likely to have
      these adverse features. High-risk AML responds poorly to available induction
      treatment and is likely to relapse despite consolidation therapy. Current data
      support an increasing understanding of prognosis but have not yet resulted in
      effective therapies for patients with high-risk disease. This review discusses
      current therapies and evolving treatment strategies for high-risk AML.

PMID- 24432898
TI  - Cotrimoxazole as a Treatment for Recurrent Idiopathic Anterior Scleritis: A
      Single-center Experience in 20 Patients.

PMID- 24432899
TI  - Multifunctional hydroxyapatite/Na(Y/Gd)F4:Yb3+,Er3+ composite fibers for drug
      delivery and dual modal imaging.
AB  - Porous hydroxyapatite (HAp) composite fibers functionalized with up-conversion
      (UC) luminescent and magnetic Na(Y/Gd)F4:Yb(3+),Er(3+) nanocrystals (NCs) have
      been fabricated via electrospinning. After transferring hydrophobic oleic acid
      capped Na(Y/Gd)F4:Yb(3+),Er(3+) NCs into aqueous solution, these water
      dispersible NCs were dispersed into precursor electrospun solution containing
      CTAB. Na(Y/Gd)F4:Yb(3+),Er(3+)@HAp composite fibers were fabricated by the high
      temperature treatment of the electrospun Na(Y/Gd)F4:Yb(3+),Er(3+) NCs decorated
      precursor fibers. The biocompatibility test on MC 3T3-E1 cells using MTT assay
      shows that the HAp composite fibers have negligible cytotoxity, which reveals the
      HAp composite fibers could be a drug carrier for drug delivery. Because the
      contrast brightening is enhanced at increased concentrations of Gd(3+), the HAp
      composite fibers can serve as T1 magnetic resonance imaging contrast agents. In
      addition, the composites uptaken by MC 3T3-E1 cells present the UC luminescent
      emission of Er(3+) under the excitation of a 980 nm near-infrared laser. The
      above findings reveal Na(Y/Gd)F4:Yb(3+),Er(3+)@HAp composite fibers have
      potential applications in drug storage/release and magnetic resonance/UC
      luminescence imaging. 

PMID- 24432903
TI  - Natural gas pipeline leaks across Washington, DC.
AB  - Pipeline safety in the United States has increased in recent decades, but
      incidents involving natural gas pipelines still cause an average of 17 fatalities
      and $133 M in property damage annually. Natural gas leaks are also the largest
      anthropogenic source of the greenhouse gas methane (CH4) in the U.S. To reduce
      pipeline leakage and increase consumer safety, we deployed a Picarro G2301 Cavity
      Ring-Down Spectrometer in a car, mapping 5893 natural gas leaks (2.5 to 88.6 ppm
      CH4) across 1500 road miles of Washington, DC. The delta(13)C-isotopic signatures
      of the methane (-38.20/00 +/- 3.90/00 s.d.) and ethane (-36.5 +/- 1.1 s.d.) and
      the CH4:C2H6 ratios (25.5 +/- 8.9 s.d.) closely matched the pipeline gas (
      39.00/00 and -36.20/00 for methane and ethane; 19.0 for CH4/C2H6). Emissions from
      four street leaks ranged from 9200 to 38,200 L CH4 day(-1) each, comparable to
      natural gas used by 1.7 to 7.0 homes, respectively. At 19 tested locations, 12
      potentially explosive (Grade 1) methane concentrations of 50,000 to 500,000 ppm
      were detected in manholes. Financial incentives and targeted programs among
      companies, public utility commissions, and scientists to reduce leaks and replace
      old cast-iron pipes will improve consumer safety and air quality, save money, and
      lower greenhouse gas emissions.

PMID- 24432905
TI  - Structure and Raman spectra in cryolitic melts: simulations with an ab initio
      interaction potential.
AB  - The Raman spectra of cryolitic melts have been calculated from molecular dynamics
      computer simulations using a polarizable ionic potential obtained by force
      fitting to ab initio electronic structure calculations. Simulations which made
      use of this ab initio derived polarizable interaction potential reproduced the
      structure and dynamical properties of crystalline cryolite, Na3AlF6, rather well.
      The transferability of the potential model from solid state to the molten state
      is tested by comparing results for the Raman spectra of melts of various
      compositions with those previously obtained with empirically developed potentials
      and with experimental data. The shapes of the spectra and their evolution with
      composition in the mixtures conform quite well to those seen experimentally, and
      we discuss the relationship between the bands seen in the spectra and the
      vibrational modes of the AlFn((3-n)) coordination complexes which are found in
      the NaF/AlF3 mixtures. The simulations thus enable a link between the structure
      of the melt as derived through Raman spectroscopy and through diffraction
      experiments. We report results for quantities which relate to the degree of cross
      linking between these coordination complexes and the diffusive properties of
      ions.

PMID- 24432906
TI  - Characterization and quantification of diacylglycerol species in biological
      extracts after one-step derivatization: a shotgun lipidomics approach.
AB  - Diacylglycerols (DAGs) are important intermediates of lipid metabolism and
      cellular signaling. It is well-known that the mass levels of DAG are altered
      under disease states. Therefore, quantitative analysis of DAGs in biological
      samples can provide critical information to uncover underlying mechanisms of
      various cellular functional disorders. Although great efforts on the analysis of
      individual DAG species have recently been made by utilizing mass spectrometry
      with or without derivatization, cost-effective and high throughput methodologies
      for identification and quantification of all DAG species including regioisomers,
      particularly in an approach of shotgun lipidomics, are still missing. Herein, we
      described a novel method for directly identifying and quantifying DAG species
      including regioisomers present in lipid extracts of biological samples after
      facile one-step derivatization with dimethylglycine based on the principles of
      multidimensional mass spectrometry-based shotgun lipidomics. The established
      method provided substantial sensitivity (low limit of quantification at
      amol/MUL), high specificity, and broad linear dynamics range (2500-fold) without
      matrix effects. By exploiting this novel method, we revealed a 16-fold increase
      of total DAG mass in the livers of ob/ob mice compared to their wild type
      controls at 4 months of age (an insulin-resistant state) versus a 5-fold
      difference between 3 month old mice (with normal insulin). These results
      demonstrated the importance and power of the method for studying biochemical
      mechanisms underpinning disease states. 

PMID- 24432909
TI  - Design of potent and selective inhibitors to overcome clinical anaplastic
      lymphoma kinase mutations resistant to crizotinib.
AB  - Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase
      inhibitor approved by the U.S. Food and Drug Administration in 2011, is
      efficacious in ALK and ROS positive patients. Under pressure of crizotinib
      treatment, point mutations arise in the kinase domain of ALK, resulting in
      resistance and progressive disease. The successful application of both structure
      based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e,
      which was potent across a broad panel of engineered ALK mutant cell lines and
      showed suitable preclinical pharmacokinetics and robust tumor growth inhibition
      in a crizotinib-resistant cell line (H3122-L1196M). 

PMID- 24432912
TI  - Acid-sensing ion channels in healthy and degenerated human intervertebral disc.
AB  - Acid-sensing ion channels (ASICs) are a family of H(+)-gated voltage-insensitive
      ion channels that respond to extracellular acidification by regulating
      transmembrane Ca(2+) flux. Moreover, ASICs can also be gated by mechanical forces
      and may function as mechanosensors. The cells of the intervertebral disc (IVD)
      have an unusual acidic and hyperosmotic microenvironment. Changes in the pH and
      osmolarity determine the viability of IVD cells and the composition of the
      extracellular matrix, and both are the basis of IVD degeneration. In this study,
      the expression of ASICs (ASIC1, ASIC2, ASIC3 and ASIC4) mRNAs and proteins in
      human healthy and degenerated IVD was evaluated by quantitative reverse
      transcription-quantitative polymerase chain reaction and Western blot. The
      distribution of ASIC proteins was determined by immunohistochemistry. The mRNAs
      for all ASICs were detected in normal human IVD, and significantly increased
      levels were found in degenerated IVD. Western blots demonstrated the presence of
      proteins with estimated molecular weights of approximately 68-72 kDa. In both the
      annulus fibrosus (AF) and nucleus pulposus (NP) of normal IVD, ASIC2 is the most
      frequently expressed ASIC followed by ASIC3, ASIC1 and ASIC4. In the AF of
      degenerated IVD, there was a significant increase in the number of ASIC1 and
      ASIC4 positive cells, whereas in the NP, we found significant increase of
      expression of ASIC1, ASIC2 and ASIC3. These results describe the occurrence and
      localization of different ASICs in human healthy IVD, and their increased
      expression in degenerated IVD, thus suggesting that ASICs may be involved in IVD
      degeneration.

PMID- 24432915
TI  - Obstructive sleep apnea syndrome and chronic kidney disease: a new cardiorenal
      risk factor.
AB  - Clinical and experimental studies revealed that sleep apnea might be an insidious
      risk factor for the progression of kidney disease and development of
      cardiovascular events by exacerbating well-known risk factors, namely
      hypertension, type 2 diabetes mellitus and obesity. Furthermore, sleep apnea also
      has a negative impact on endothelial function. Therefore, sleep apnea might be
      defined as a new cardiorenal risk factor. In this review, we aimed to summarize
      the evidences supporting the complex inter-relations between sleep apnea and
      development and progression of chronic kidney disease.

PMID- 24432916
TI  - Parental incarceration and child mortality in Denmark.
AB  - OBJECTIVES: We used Danish registry data to examine the association between
      parental incarceration and child mortality risk. METHODS: We used a sample of all
      Danish children born in 1991 linked with parental information. We conducted
      discrete-time survival analysis separately for boys (n = 30 146) and girls (n =
      28 702) to estimate the association of paternal and maternal incarceration with
      child mortality, controlling for parental sociodemographic characteristics. We
      followed the children until age 20 years or death, whichever came first. RESULTS:
      Results indicated a positive association between paternal and maternal
      imprisonment and male child mortality. Paternal imprisonment was associated with
      lower child mortality risks for girls. The relationship between maternal
      imprisonment and female child mortality changed directions depending on the
      model, suggesting no clear association. CONCLUSIONS: These results indicate that
      the incarceration of a parent may influence child mortality but that it is
      important to consider the gender of both the child and the incarcerated parent.

PMID- 24432917
TI  - Firearm and nonfirearm homicide in 5 South African cities: a retrospective
      population-based study.
AB  - OBJECTIVE: We assessed the effectiveness of South Africa's Firearm Control Act
      (FCA), passed in 2000, on firearm homicide rates compared with rates of
      nonfirearm homicide across 5 South African cities from 2001 to 2005. METHODS: We
      conducted a retrospective population-based study of 37 067 firearm and nonfirearm
      homicide cases. Generalized linear models helped estimate and compare time trends
      of firearm and nonfirearm homicides, adjusting for age, sex, race, day of week,
      city, year of death, and population size. RESULTS: There was a statistically
      significant decreasing trend regarding firearm homicides from 2001, with an
      adjusted year-on-year homicide rate ratio of 0.864 (95% confidence interval [CI]
      = 0.848, 0.880), representing a decrease of 13.6% per annum. The year-on-year
      decrease in nonfirearm homicide rates was also significant, but considerably
      lower at 0.976 (95% CI = 0.954, 0.997). Results suggest that 4585 (95% CI = 4427,
      4723) lives were saved across 5 cities from 2001 to 2005 because of the FCA.
      CONCLUSIONS: Strength, timing and consistent decline suggest stricter gun control
      mediated by the FCA accounted for a significant decrease in homicide overall, and
      firearm homicide in particular, during the study period.

PMID- 24432918
TI  - Estimating acute viral hepatitis infections from nationally reported cases.
AB  - OBJECTIVES: Because only a fraction of patients with acute viral hepatitis A, B,
      and C are reported through national surveillance to the Centers for Disease
      Control and Prevention, we estimated the true numbers. METHODS: We applied a
      simple probabilistic model to estimate the fraction of patients with acute
      hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would
      have sought health care tests, and would have been reported to health officials
      in 2011. RESULTS: For hepatitis A, the frequencies of symptoms (85%), care
      seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0
      infections per reported case). For hepatitis B, the frequencies of symptoms
      (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5
      infections per reported case). For hepatitis C, the frequency of symptoms among
      injection drug users (13%) and those infected otherwise (48%), proportion seeking
      care (88%), and percentage reported (53%) indicated 17 100 infections (12.3
      infections per reported case). CONCLUSIONS: These adjustment factors will allow
      state and local health authorities to estimate acute hepatitis infections locally
      and plan prevention activities accordingly.

PMID- 24432919
TI  - Body mass index and risk of death in Asian Americans.
AB  - OBJECTIVES: We investigated the association between body mass index (BMI) and
      mortality among Asian Americans. METHODS: We pooled data from prospective cohort
      studies with 20 672 Asian American adults with no baseline cancer or heart
      disease history. We estimated hazard ratios and 95% confidence intervals (CIs)
      with Cox proportional hazards models. RESULTS: A high, but not low, BMI was
      associated with increased risk of total mortality among individuals aged 35 to 69
      years. The BMI was not related to total mortality among individuals aged 70 years
      and older. With a BMI 22.5 to < 25 as the reference category among never-smokers
      aged 35 to 69 years, the hazard ratios for total mortality were 0.83 (95% CI =
      0.47, 1.47) for BMI 15 to < 18.5; 0.91 (95% CI = 0.62, 1.32) for BMI 18.5 to <
      20; 1.08 (95% CI = 0.86, 1.36) for BMI 20 to < 22.5; 1.14 (95% CI = 0.90, 1.44)
      for BMI 25 to < 27.5; 1.13 (95% CI = 0.79, 1.62) for BMI 27.5 to < 30; 1.82 (95%
      CI = 1.25, 2.64) for BMI 30 to < 35; and 2.09 (95% CI = 1.06, 4.11) for BMI 35 to
      50. Higher BMI was also related to increased cardiovascular disease and cancer
      mortality. CONCLUSIONS: High BMI is associated with increased mortality risk
      among Asian Americans.

PMID- 24432920
TI  - Geographic residency status and census tract socioeconomic status as determinants
      of colorectal cancer outcomes.
AB  - OBJECTIVES: We examined the impact of geographic residency status and census
      tract (CT)-level socioeconomic status (SES) on colorectal cancer (CRC) outcomes.
      METHODS: This was a retrospective cohort study of patients diagnosed with CRC in
      Georgia for the years 2000 through 2007. Study outcomes were late-stage disease
      at diagnosis, receipt of treatment, and survival. RESULTS: For colon cancer,
      residents of lower-middle-SES and low-SES census tracts had decreased odds of
      receiving surgery. Rural, lower-middle-SES, and low-SES residents had decreased
      odds of receiving chemotherapy. For patients with rectal cancer, suburban
      residents had increased odds of receiving radiotherapy, but low SES resulted in
      decreased odds of surgery. For survival, rural residents experienced a partially
      adjusted 14% (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.07,
      1.22) increased risk of death following diagnosis of CRC that was somewhat
      explained by treatment differences and completely explained by CT-level SES.
      Lower-middle- and low-SES participants had an adjusted increased risk of death
      following diagnosis for CRC (lower-middle: HR = 1.16; 95% CI = 1.10, 1.22; low:
      HR = 1.24; 95% CI = 1.16, 1.32). CONCLUSIONS: Future efforts should focus on
      developing interventions and policies that target rural residents and lower SES
      areas to eliminate disparities in CRC-related outcomes.

PMID- 24432921
TI  - Body mass index categories and mortality risk in US adults: the effect of
      overweight and obesity on advancing death.
AB  - OBJECTIVES: We examined the association of body mass index with all-cause and
      cardiovascular disease (CVD)-specific mortality risks among US adults and
      calculated the rate advancement period by which death is advanced among the
      exposed groups. METHODS: We used data from the Third National Health and
      Nutrition Examination Survey (1988-1994) linked to the National Death Index
      mortality file with follow-up to 2006 (n = 16 868). We used Cox proportional
      hazards regression to estimate the rate of dying and rate advancement period for
      all-cause and CVD-specific mortality for overweight and obese adults relative to
      their normal-weight counterparts. RESULTS: Compared with normal-weight adults,
      obese adults had at least 20% significantly higher rate of dying of all-cause or
      CVD. These rates advanced death by 3.7 years (grades II and III obesity) for all
      cause mortality and between 1.6 (grade I obesity) and 5.0 years (grade III
      obesity) for CVD-specific mortality. The burden of obesity was greatest among
      adults aged 45 to 64 years for all-cause and CVD-specific mortality and among
      women for all-cause mortality. CONCLUSIONS: These findings highlight the impact
      of the obesity epidemic on mortality risk and premature deaths among US adults.

PMID- 24432922
TI  - Government leadership in addressing public health priorities: strides and delays
      in electronic laboratory reporting in the United States.
AB  - For nearly a decade, interest groups, from politicians to economists to
      physicians, have touted digitization of the nation's health information. One
      frequently mentioned benefit is the transmission of information electronically
      from laboratories to public health personnel, allowing them to rapidly analyze
      and act on these data. Switching from paper to electronic laboratory reports
      (ELRs) was thought to solve many public health surveillance issues, including
      workload, accuracy, and timeliness. However, barriers remain for both
      laboratories and public health agencies to realize the full benefits of ELRs. The
      New York City experience highlights several successes and challenges of
      electronic reporting and is supported by peer-reviewed literature. Lessons
      learned from ELR systems will benefit efforts to standardize electronic medical
      records reporting to health departments. 

PMID- 24432923
TI  - Cluster-randomized controlled trial of an HIV/sexually transmitted infection risk
      reduction intervention for South African men.
AB  - OBJECTIVES: We tested the efficacy of a sexual risk-reduction intervention for
      men in South Africa, where heterosexual exposure is the main mode of HIV
      transmission. METHODS: Matched-pairs of neighborhoods in Eastern Cape Province,
      South Africa, were randomly selected and within pairs randomized to 1 of 2
      interventions based on social cognitive theory and qualitative research:
      HIV/sexually transmitted infection (STI) risk-reduction, targeting condom use, or
      attention-matched control, targeting health issues unrelated to sexual risks.
      Sexually active men aged 18 to 45 years were eligible. The primary outcome was
      consistent condom use in the past 3 months. RESULTS: Of 1181 participants, 1106
      (93.6%) completed the 12-month follow-up. HIV and STI risk-reduction participants
      had higher odds of reporting consistent condom use (odds ratio [OR] = 1.32; 95%
      confidence interval [CI] = 1.03, 1.71) and condom use at last vaginal intercourse
      (OR = 1.40; 95% CI = 1.08, 1.82) than did attention-control participants,
      adjusting for baseline prevalence. No differences were observed on unprotected
      intercourse or multiple partnerships. Findings did not differ for sex with steady
      as opposed to casual partners. CONCLUSIONS: Behavioral interventions specifically
      targeting men can contribute to efforts to reduce sexual risk behaviors in South
      Africa.

PMID- 24432924
TI  - Global childhood unintentional injury study: multisite surveillance data.
AB  - OBJECTIVES: We aimed to analyze the epidemiology of childhood unintentional
      injuries presenting to hospitals in 5 select sites in low- and middle-income
      countries (LMICs) (Bangladesh, Colombia, Egypt, Malaysia, and Pakistan). METHODS:
      We collected standardized data from children ages 0 to 12 years at participating
      emergency departments (EDs) in 2007. Statistical analyses were conducted to
      compare the characteristics of these injuries and to explore the determinants of
      injury outcomes. RESULTS: Among 2686 injured children, falls (50.4%) and road
      traffic injuries (16.4%) were the most common, affecting boys more often (64.7%).
      Home injuries were more common among younger children (average 5.41 vs 7.06
      years) and girls (38.2% vs 31.7%). Following an ED visit, 24% of injured children
      were admitted to the hospital, and 6 died. Injury outcomes were associated with
      risk factors, such as age and sex, to varying extents. CONCLUSIONS: Standardized
      ED surveillance revealed unintentional injuries are a threat to child health. The
      majority of events took place inside the home, challenging traditional concepts
      of children's safety and underscoring the need for intensified context
      appropriate injury prevention.

PMID- 24432925
TI  - Associations between driving performance and engaging in secondary tasks: a
      systematic review.
AB  - We conducted a systematic review and meta-analysis of the literature examining
      the relationship between driving performance and engaging in secondary tasks. We
      extracted data from abstracts of 206 empirical articles published between 1968
      and 2012 and developed a logistic regression model to identify correlates of a
      detrimental relationship between secondary tasks and driving performance. Of 350
      analyses, 80% reported finding a detrimental relationship. Studies using
      experimental designs were 37% less likely to report a detrimental relationship (P
      = .014). Studies examining mobile phone use while driving were 16% more likely to
      find such a relationship (P = .009). Quasi-experiments can better determine the
      effects of secondary tasks on driving performance and consequently serve to
      inform policymakers interested in reducing distracted driving and increasing
      roadway safety.

PMID- 24432926
TI  - The state of transgender health care: policy, law, and medical frameworks.
AB  - I review the current status of transgender people's access to health care in the
      United States and analyze federal policies regarding health care services for
      transgender people and the limitations thereof. I suggest a preliminary outline
      to enhance health care services and recommend the formulation of explicit federal
      policies regarding the provision of health care services to transgender people in
      accordance with recently issued medical care guidelines, allocation of research
      funding, education of health care workers, and implementation of existing
      nondiscrimination policies. Current policies denying medical coverage for sex
      reassignment surgery contradict standards of medical care and must be amended. 

PMID- 24432927
TI  - Early effects of the San Francisco paid sick leave policy.
AB  - OBJECTIVES: We examined employers' responses to San Francisco, California's 2007
      Paid Sick Leave Ordinance. METHODS: We used the 2009 Bay Area Employer Health
      Benefits Survey to describe sick leave policy changes and the policy's effects on
      firm (n = 699) operations. RESULTS: The proportion of firms offering paid sick
      leave in San Francisco grew from 73% in 2006 to 91% in 2009, with large firms
      (99%) more likely to offer sick leave than are small firms (86%) in 2009. Most
      firms (57%) did not make any changes to their sick leave policy, although 17%
      made a major change to sick leave policy to comply with the law. Firms beginning
      to offer sick leave reported reductions in other benefits (39%), worse
      profitability (32%), and increases in prices (18%) but better employee morale
      (17%) and high support for the policy (71%). Many employers (58%) reported some
      difficulty understanding legal requirements, complying administratively, or
      reassigning work responsibilities. CONCLUSIONS: There was a substantial increase
      in paid sick leave coverage after the mandate. Employers reported some
      difficulties in complying with the law but supported the policy overall.

PMID- 24432928
TI  - Sugary beverage tax policy: lessons learned from tobacco.
AB  - Excise taxes on sugary beverages have been proposed as a method to replicate the
      public health success of tobacco control and to generate revenue. As policymakers
      increase efforts to pass sugary beverage taxes, they can anticipate that
      manufacturers will emulate the strategies employed by tobacco companies in their
      attempts to counteract the impact of such taxes. Policymakers should therefore
      consider 2 complementary laws-minimum price laws and prohibitions on coupons and
      discounting-to accomplish the intended price increase. 

PMID- 24432929
TI  - McCauley and Miller respond.

PMID- 24432930
TI  - Heikkila et al. respond.

PMID- 24432931
TI  - Public health and climate change adaptation at the federal level: one agency's
      response to Executive Order 13514.
AB  - Climate change will likely have adverse human health effects that require federal
      agency involvement in adaptation activities. In 2009, President Obama issued
      Executive Order 13514, Federal Leadership in Environmental, Energy, and Economic
      Performance. The order required federal agencies to develop and implement climate
      change adaptation plans. The Centers for Disease Control and Prevention (CDC), as
      part of a larger Department of Health and Human Services response to climate
      change, is developing such plans. We provide background on Executive Orders,
      outline tenets of climate change adaptation, discuss public health adaptation
      planning at both the Department of Health and Human Services and the CDC, and
      outline possible future CDC efforts. We also consider how these activities may be
      better integrated with other adaptation activities that manage emerging health
      threats posed by climate change. 

PMID- 24432932
TI  - Determinants of receipt of recommended preventive services: implications for the
      Affordable Care Act.
AB  - OBJECTIVES: We examined preventive care use by nonelderly adults (aged 18-64
      years) before the Affordable Care Act (ACA) and considered the contributions of
      insurance coverage and other factors to service use patterns. METHODS: We used
      data from the 2005-2010 Medical Expenditure Panel Survey to measure the receipt
      of 8 recommended preventive services. We examined gaps in receipt of services for
      adults with incomes below 400% of the federal poverty level compared with higher
      incomes. We then used a regression-based decomposition analysis to consider
      factors that explain the gaps in service use by income. RESULTS: There were large
      income-related disparities in preventive care receipt for nonelderly adults.
      Differences in insurance coverage explain 25% to 40% of the disparities in
      preventive service use by income, but education, age, and health status are also
      important drivers. CONCLUSIONS: Expanding coverage to lower-income adults through
      the ACA is expected to increase their preventive care use. However, the
      importance of education, age, and health status in explaining income-related gaps
      in service use indicates that the ACA cannot address all barriers to preventive
      care and additional interventions may be necessary.

PMID- 24432933
TI  - Wesseling et al. respond.

PMID- 24432934
TI  - Uninsured veterans who will need to obtain insurance coverage under the patient
      protection and affordable care act.
AB  - OBJECTIVES: We examined the number and clinical needs of uninsured veterans,
      including those who will be eligible for the Medicaid expansion and health
      insurance exchanges in 2014. METHODS: We analyzed weighted data for 8710 veterans
      from the 2010 National Survey of Veterans, classifying it by veterans' age,
      income, household size, and insurance status. RESULTS: Of 22 million veterans,
      about 7%, or more than 1.5 million, were uninsured and will need to obtain
      coverage by enrolling in US Department of Veterans Affairs (VA) care or the
      Medicaid expansion or by participating in the health insurance exchanges. Of
      those uninsured, 55%, or more than 800 000, are likely eligible for the Medicaid
      expansion if states implement it. Compared with veterans with any health
      coverage, those who were uninsured were younger and more likely to be single,
      Black, and low income and to have been deployed to Iraq and Afghanistan.
      CONCLUSIONS: The Patient Protection and Affordable Care Act is likely to have a
      considerable impact on uninsured veterans, which may have implications for the
      VA, the Medicaid expansion, and the health insurance exchanges.

PMID- 24432936
TI  - Friedman and Parrish respond.

PMID- 24432935
TI  - Change in walking and body mass index following residential relocation: the multi
      ethnic study of atherosclerosis.
AB  - OBJECTIVES: We investigated whether moving to neighborhoods with closer proximity
      of destinations and greater street connectivity was associated with more walking,
      a greater probability of meeting the "Every Body Walk!" campaign goals (>= 150
      minutes/week of walking), and reductions in body mass index (BMI). METHODS: We
      linked longitudinal data from 701 participants, who moved between 2 waves of the
      Multi-Ethnic Study of Atherosclerosis (2004-2012), to a neighborhood walkability
      measure (Street Smart Walk Score) for each residential location. We used fixed
      effects models to estimate if changes in walkability resulting from relocation
      were associated with simultaneous changes in walking behaviors and BMI. RESULTS:
      Moving to a location with a 10-point higher Walk Score was associated with a
      16.04 minutes per week (95% confidence interval [CI] = 5.13, 29.96) increase in
      transport walking, 11% higher odds of meeting Every Body Walk! goals through
      transport walking (adjusted odds ratio = 1.11; 95% CI = 1.02, 1.21), and a 0.06
      kilogram per meters squared (95% CI = -0.12, -0.01) reduction in BMI. Change in
      walkability was not associated with change in leisure walking. CONCLUSIONS: Our
      findings illustrated the potential for neighborhood infrastructure to support
      health-enhancing behaviors and overall health of people in the United States.

PMID- 24432937
TI  - Chronic kidney disease among agricultural workers in Central America.

PMID- 24432939
TI  - Potentially misleading conclusions: job strain and health behaviors.

PMID- 24432938
TI  - Work organization and health among immigrant women: Latina manual workers in
      North Carolina.
AB  - OBJECTIVES: We sought to describe work organization attributes for employed
      immigrant Latinas and determine associations of work organization with physical
      health, mental health, and health-related quality of life. METHODS: We conducted
      a cross-sectional survey with 319 employed Latinas in western North Carolina
      (2009-2011). Measures included job demands (heavy load, awkward posture,
      psychological demand), decision latitude (skill variety, job control), support
      (supervisor control, safety climate), musculoskeletal symptoms, mental health
      (depressive symptoms), and mental (MCS) and physical component score (PCS) health
      related quality of life. RESULTS: Three fifths reported musculoskeletal symptoms.
      Mean scores for depression, MCS, and PCS were 6.2 (SE = 0.2), 38.3 (SE = 0.5),
      and 42.8 (SE = 0.3), respectively. Greater job demands (heavy load, awkward
      posture, greater psychological demand) were associated with more musculoskeletal
      and depressive symptoms and worse MCS. Less decision latitude (lower skill
      variety, job control) was associated with more musculoskeletal and depressive
      symptoms. Greater support (supervisor's power and safety climate) was associated
      with fewer depressive symptoms and better MCS. CONCLUSIONS: Work organization
      should be considered to improve occupational health of vulnerable women workers.
      Additional research should delineate the links between work organization and
      health among vulnerable workers.

PMID- 24432940
TI  - Addressing mass incarceration: a clarion call for public health.

PMID- 24432941
TI  - Cost-effectiveness of pit-and-fissure sealants on primary molars in Medicaid
      enrolled children.
AB  - OBJECTIVES: We compared the incremental cost-effectiveness of 2 primary molar
      sealant strategies-always seal and never seal-with standard care for Medicaid
      enrolled children. METHODS: We used Iowa Medicaid claims data (2008-2011),
      developed a tooth-level Markov model for 10 000 teeth, and compared costs,
      treatment avoided, and incremental cost per treatment avoided for the 2 sealant
      strategies with standard care. RESULTS: In 10 000 simulated teeth, standard care
      cost $214 510, always seal cost $232 141, and never seal cost $186 010. Relative
      to standard care, always seal reduced the number of restorations to 340 from
      2389, whereas never seal increased restorations to 2853. Compared with standard
      care, always seal cost $8.12 per restoration avoided (95% confidence interval
      [CI] = $4.10, $12.26; P <= .001). Compared with never seal, standard care cost
      $65.62 per restoration avoided (95% CI = $52.99, $78.26; P <= .001). CONCLUSIONS:
      Relative to standard care, always sealing primary molars is more costly but
      reduces subsequent dental treatment. Never sealing costs less but leads to more
      treatment. State Medicaid programs that do not currently reimburse dentists for
      primary molar sealants should consider reimbursement for primary molar sealant
      procedures as a population-based strategy to prevent tooth decay and reduce later
      treatment needs in vulnerable young children.

PMID- 24432942
TI  - Job strain and health-related lifestyle.

PMID- 24432943
TI  - Intimate partner homicide and corollary victims in 16 states: National Violent
      Death Reporting System, 2003-2009.
AB  - OBJECTIVES: We estimated the frequency and examined the characteristics of
      intimate partner homicide and related deaths in 16 US states participating in the
      National Violent Death Reporting System (NVDRS), a state-based surveillance
      system. METHODS: We used a combination of quantitative and qualitative methods to
      analyze NVDRS data from 2003 to 2009. We selected deaths linked to intimate
      partner violence for analysis. RESULTS: Our sample comprised 4470 persons who
      died in the course of 3350 intimate partner violence-related homicide incidents.
      Intimate partners and corollary victims represented 80% and 20% of homicide
      victims, respectively. Corollary homicide victims included family members, new
      intimate partners, friends, acquaintances, police officers, and strangers.
      CONCLUSIONS: Our findings, from the first multiple-state study of intimate
      partner homicide and corollary homicides, demonstrate that the burden of intimate
      partner violence extends beyond the couple involved. Systems (e.g., criminal
      justice, medical care, and shelters) whose representatives routinely interact
      with victims of intimate partner violence can help assess the potential for
      lethal danger, which may prevent intimate partner and corollary victims from
      harm.

PMID- 24432944
TI  - Racial discrimination in health care settings: does insurance matter?

PMID- 24432946
TI  - Measurement of gender equity: a clarification.

PMID- 24432945
TI  - Medical marijuana laws and suicides by gender and age.
AB  - OBJECTIVES: We estimated the association between legalizing medical marijuana and
      suicides. METHODS: We obtained state-level suicide data from the National Vital
      Statistics System's Mortality Detail Files for 1990-2007. We used regression
      analysis to examine the association between medical marijuana legalization and
      suicides per 100 000 population. RESULTS: After adjustment for economic
      conditions, state policies, and state-specific linear time trends, the
      association between legalizing medical marijuana and suicides was not
      statistically significant at the .05 level. However, legalization was associated
      with a 10.8% (95% confidence interval [CI] = -17.1%, -3.7%) and 9.4% (95% CI = 
      16.1%, -2.4%) reduction in the suicide rate of men aged 20 through 29 years and
      30 through 39 years, respectively. Estimates for females were less precise and
      sensitive to model specification. CONCLUSIONS: Suicides among men aged 20 through
      39 years fell after medical marijuana legalization compared with those in states
      that did not legalize. The negative relationship between legalization and
      suicides among young men is consistent with the hypothesis that marijuana can be
      used to cope with stressful life events. However, this relationship may be
      explained by alcohol consumption. The mechanism through which legalizing medical
      marijuana reduces suicides among young men remains a topic for future study.

PMID- 24432947
TI  - James Edmund Reeves. 1883.

PMID- 24432948
TI  - The high prevalence of incarceration history among Black men who have sex with
      men in the United States: associations and implications.
AB  - OBJECTIVES: We examined lifetime incarceration history and its association with
      key characteristics among 1553 Black men who have sex with men (BMSM) recruited
      in 6 US cities. METHODS: We conducted bivariate analyses of data collected from
      the HIV Prevention Trials Network 061 study from July 2009 through December 2011
      to examine the relationship between incarceration history and demographic and
      psychosocial variables predating incarceration and multivariate logistic
      regression analyses to explore the associations between incarceration history and
      demographic and psychosocial variables found to be significant. We then used
      multivariate logistic regression models to explore the independent association
      between incarceration history and 6 outcome variables. RESULTS: After adjusting
      for confounders, we found that increasing age, transgender identity, heterosexual
      or straight identity, history of childhood violence, and childhood sexual
      experience were significantly associated with incarceration history. A history of
      incarceration was also independently associated with any alcohol and drug use in
      the past 6 months. CONCLUSIONS: The findings highlight an elevated lifetime
      incarceration history among a geographically diverse sample of BMSM and the need
      to adequately assess the impact of incarceration among BMSM in the United States.

PMID- 24432949
TI  - The courts and public health: caught in a pincer movement.
AB  - Public health practitioners are familiar with the general outlines of legal
      authority and with judicial standards for reviewing public health regulations.
      What may not be as familiar are 3 emerging judicial doctrines that pose
      considerable risks to public health initiatives. We explain the contentious
      series of judicial rulings that now place health departments' broad grant of
      authority in jeopardy. One doctrine invokes the First Amendment to limit
      regulatory authority. The second involves the Supreme Court's reinterpretation of
      federalism to limit both federal and state public health interventions. The third
      redefines the standard of evidence required to support regulations. Together,
      these judicial trends create a pincer movement that places substantial new
      burdens on the ability of health departments to protect health. 

PMID- 24432950
TI  - Health information technology and the primary care information project.

PMID- 24432951
TI  - Suicidal ideation among community-dwelling adults in the United States.
AB  - OBJECTIVES: We examined the prevalence and correlates of past-year suicidal
      ideation among US community-dwelling adults. METHODS: We examined data from 183
      100 persons aged 18 years or older (including 9800 sampled adults with past-year
      suicidal ideation) who participated in the 2008-2011 National Survey on Drug Use
      and Health. We applied descriptive analyses and pooled and stratified (by age and
      major depression) multivariate logistic regression models. RESULTS: The
      prevalence of past-year suicidal ideation among younger adults (6.6% among those
      aged 18-25 years and 4.0% among those aged 26-49 years) was higher than was that
      among adults aged 50 years or older (2.5%). The prevalence of suicidal ideation
      was high among adults with major depression (26.3%), adults with both major
      depression and substance use disorder (37.7%), and adults who received mental
      health treatment but perceived unmet treatment need (33.5%). CONCLUSIONS: Many
      risk and protective factors of suicidal ideation are dynamic and vary by age or
      major depression. These results have important implications for developing
      specific suicide prevention strategies that help screen, assess, and treat
      suicidal adults at the earliest possible time.

PMID- 24432953
TI  - Optic neuropathy secondary to Linezolid for multidrug-resistant mycobacterial
      spinal tuberculosis.
AB  - AIM: To report a case of optic neuropathy secondary to Linezolid, second line
      anti tuberculosis agent. CASE REPORT: 22 year Indian male with multidrug
      resistant spinal tuberculosis and TB meningitis was started on second line anti
      tuberculosis drugs. Within one month of onset of second line anti TB drug, he was
      noted to have optic neuropathy in both eyes. Visual field and electro diagnostics
      suggested optic neuropathy. DISCUSSION: Linezolid is a synthetic oxazolidinone
      broad spectrum antibiotic and has been in off label use for multidrug resistant
      tuberculosis (MDR-TB). There are very scattered case reports of optic neuropathy
      secondary to use of this off label drug. In our case, the optic neuropathy was
      however reversible on stoppage of the drug. CONCLUSION: It seems prudent that
      baseline ophthalmological evaluation to be done for all patients to be subjected
      for treatment with this drug for any short term or long term therapy.

PMID- 24432955
TI  - One of us? Novel strategy aims at getting chimpanzees recognized as legal
      persons.

PMID- 24432956
TI  - Pigmentary uveitis.

PMID- 24432957
TI  - Veterinary clinical decision-making: cognitive biases, external constraints, and
      strategies for improvement.

PMID- 24432958
TI  - What is your diagnosis? Gastroesophageal intussusception.

PMID- 24432959
TI  - What is your diagnosis? Calcinosis circumscripta.

PMID- 24432960
TI  - Pathology in practice. Primitive neuroectodermal tumor (PNET) with ependymal
      differentiation.

PMID- 24432961
TI  - Feasibility of depopulation of a large feedlot during a foot-and-mouth disease
      outbreak.
AB  - OBJECTIVE: To examine the feasibility of depopulation of a large feedlot during a
      foot-and-mouth disease (FMD) outbreak in the United States. DESIGN: Delphi survey
      followed by facilitated discussion. SAMPLE: 27 experts, including veterinary
      toxicologists and pharmacologists, animal welfare experts, feedlot managers, and
      consulting veterinarians. PROCEDURES: 4 veterinary pharmacologists, 5 veterinary
      toxicologists, 4 animal welfare experts, 26 consulting veterinarians, and 8
      feedlot managers were invited to participate in a Delphi survey to identify
      methods for depopulation of a large feedlot during an FMD outbreak. A facilitated
      discussion that included 1 pharmacologist, 1 toxicologist, 1 animal welfare
      expert, 2 consulting veterinarians, and 2 feedlot managers was held to review the
      survey results. RESULTS: 27 of 47 invited experts participated in the Delphi
      survey. Survey consensus was that, although several toxic agents would
      effectively cause acute death in a large number of animals, all of them had
      substantial animal welfare concerns. Pentobarbital sodium administered IV was
      considered the most effective pharmacological agent for euthanasia, and xylazine
      was considered the most effective sedative. Animal welfare concerns following
      administration of a euthanasia solution IV or a penetrating captive bolt were
      minimal; however, both veterinarians and feedlot managers felt that use of a
      captive bolt would be inefficient for depopulation. Veterinarians were extremely
      concerned about public perception, human safety, and timely depopulation of a
      large feedlot during an FMD outbreak. CONCLUSIONS AND CLINICAL RELEVANCE:
      Depopulation of a large feedlot during an FMD outbreak would be difficult to
      complete in a humane and timely fashion.

PMID- 24432962
TI  - Multicenter prospective evaluation of dogs with trauma.
AB  - OBJECTIVE: To determine hospital admission variables for dogs with trauma
      including values determined with scoring systems (animal trauma triage [ATT],
      modified Glasgow coma scale [MGCS], and acute patient physiologic and laboratory
      evaluation [APPLE] scores) and the usefulness of such variables for the
      prediction of outcome (death vs survival to hospital discharge). DESIGN:
      Prospective, multicenter, cohort study. ANIMALS: 315 client-owned dogs.
      PROCEDURES: By use of a Web-based data capture system, trained personnel
      prospectively recorded admission ATT, MGCS, and APPLE scores; clinical and
      laboratory data; and outcome (death vs survival to discharge) for dogs with
      trauma at 4 veterinary teaching hospitals during an 8-week period. RESULTS: Cause
      of injury was most commonly blunt trauma (173/315 [54.9%]) followed by
      penetrating trauma (107/315 [34.0%]), or was unknown (35/315 [11.1%]). Of the 315
      dogs, 285 (90.5%) survived to hospital discharge. When 16 dogs euthanized because
      of cost were excluded, dogs with blunt trauma were more likely to survive,
      compared with dogs with penetrating trauma (OR, 8.5). The ATT (OR, 2.0) and MGCS
      (OR, 0.47) scores and blood lactate concentration (OR, 1.5) at the time of
      hospital admission were predictive of outcome. Surgical procedures were performed
      for 157 (49.8%) dogs; surgery was associated with survival to discharge (OR,
      7.1). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated ATT and MGCS scores
      were useful for prediction of outcome for dogs evaluated because of trauma.
      Penetrating trauma, low blood lactate concentration, and performance of surgical
      procedures were predictive of survival to hospital discharge. The methods enabled
      collection of data for a large number of dogs in a short time.

PMID- 24432963
TI  - Evaluation of the risk and age of onset of cancer and behavioral disorders in
      gonadectomized Vizslas.
AB  - OBJECTIVE: To investigate associations between age at gonadectomy and estimated
      risk or age at diagnosis of neoplastic and behavioral disorders in Vizslas.
      DESIGN: Retrospective cohort study. ANIMALS: 2,505 Vizslas born between 1992 and
      2008. PROCEDURES: Data on demographics, gonadectomy status, and age at diagnosis
      of disease or disorder were obtained with an anonymous online survey and
      analyzed. RESULTS: Dogs gonadectomized at <= 6 months, between 7 and 12 months,
      or at > 12 months of age had significantly increased odds of developing mast cell
      cancer, lymphoma, all other cancers, all cancers combined, and fear of storms,
      compared with the odds for sexually intact dogs. Females gonadectomized at <= 12
      months of age and males and females gonadectomized at > 12 months of age had
      significantly increased odds of developing hemangiosarcoma, compared with the
      odds for sexually intact dogs. Dogs gonadectomized at <= 6 months of age had
      significantly increased odds of developing a behavioral disorder. The younger the
      age at gonadectomy, the earlier the mean age at diagnosis of mast cell cancer,
      cancers other than mast cell, hemangiosarcoma, lymphoma, all cancers combined, a
      behavioral disorder, or fear of storms. CONCLUSIONS AND CLINICAL RELEVANCE:
      Additional studies are needed on the biological effects of removing gonadal
      hormones and on methods to render dogs infertile that do not involve gonadectomy.
      Veterinarians should discuss the benefits and possible adverse effects of
      gonadectomy with clients, giving consideration to the breed of dog, the owner's
      circumstances, and the anticipated use of the dog.

PMID- 24432964
TI  - Risk factors associated with the development of chronic kidney disease in cats
      evaluated at primary care veterinary hospitals.
AB  - OBJECTIVE: To identify risk factors associated with diagnosis of chronic kidney
      disease (CKD) in cats. DESIGN: Retrospective case-control study. ANIMALS: 1,230
      cats with a clinical diagnosis of CKD, serum creatinine concentration > 1.6
      mg/dL, and urine specific gravity < 1.035 and 1,230 age-matched control cats.
      PROCEDURES: Data on putative risk factors for CKD were extracted for multivariate
      logistic regression analysis from the medical records of cats brought to 755
      primary care veterinary hospitals. For a subset of cats evaluated 6 to 12 months
      prior to the date of CKD diagnosis or control group inclusion, the percentage
      change in body weight between those dates as well as clinical signs at the
      earlier date were analyzed for associations with CKD development. RESULTS: Risk
      factors for CKD in cats included thin body condition, prior periodontal disease
      or cystitis, anesthesia or documented dehydration in the preceding year, being a
      neutered male (vs spayed female), and living anywhere in the United States other
      than the northeast. The probability of CKD decreased with increasing body weight
      in nondehydrated cats, domestic shorthair breed, and prior diagnosis of diabetes
      mellitus and increased when vomiting, polyuria or polydipsia, appetite or energy
      loss, or halitosis was present at the time of diagnosis or control group
      inclusion but not when those signs were reported 6 to 12 months earlier. Median
      weight loss during the preceding 6 to 12 months was 10.8% and 2.1% in cats with
      and without CKD, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The
      probability of CKD diagnosis in cats was influenced by several variables; recent
      weight loss, particularly in combination with the other factors, warrants
      assessment of cats for CKD.

PMID- 24432965
TI  - Evaluation of the radiographic infrapatellar fat pad sign of the contralateral
      stifle joint as a risk factor for subsequent contralateral cranial cruciate
      ligament rupture in dogs with unilateral rupture: 96 cases (2006-2007).
AB  - OBJECTIVE: To determine prevalence of the contralateral radiographic
      infrapatellar fat pad sign and contralateral radiographic degenerative sign
      (degenerative changes) and evaluate both signs as risk factors for subsequent
      contralateral cranial cruciate ligament (CrCL) rupture in dogs with unilateral
      CrCL rupture. DESIGN: Retrospective cohort study. ANIMALS: 96 dogs with
      unilateral CrCL rupture and 22 dogs with bilateral CrCL rupture. PROCEDURES: Dogs
      with unilateral CrCL rupture were classified as having normal (n = 84) or
      abnormal (12) contralateral stifle joints on the basis of joint palpation.
      Associations between potential predictive variables and rates of subsequent
      contralateral CrCL rupture were evaluated. RESULTS: Of the 84 dogs with
      unilateral CrCL rupture in which the contralateral stifle joint was palpably
      normal, 29 (34.5%) had a contralateral fat pad sign and 31 (36.9%) had a
      degenerative sign. All dogs with unilateral CrCL rupture in which the
      contralateral stifle joint was palpably abnormal had a contralateral fat pad sign
      and degenerative sign. The contralateral fat pad sign was the most important risk
      factor for subsequent rupture of the contralateral CrCL. For dogs with unilateral
      CrCL rupture and palpably normal contralateral stifle joint with and without a
      contralateral fat pad sign, median time to subsequent rupture was 421 and 1,688
      days, respectively, and the 3-year probability of subsequent rupture was 85.3%
      and 24.9%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bilateral stifle
      joint radiography should be performed for all dogs with CrCL rupture. Bilateral
      stifle joint arthroscopy should be considered for dogs with a contralateral fat
      pad sign.

PMID- 24432966
TI  - Dental radiographic findings in cats with chronic gingivostomatitis (2002-2012).
AB  - OBJECTIVE: To compare dental radiographic findings in cats with and without
      feline chronic gingivostomatitis (FCGS). DESIGN: Retrospective case-control
      study. ANIMALS: 101 cats with FCGS (cases) and 101 cats with other oral diseases
      (controls). PROCEDURES: Controls were age- and treatment date-matched with cases.
      Conventional full-mouth dental radiographic views were evaluated for
      distribution, pattern, and severity of alveolar bone loss (periodontitis), tooth
      resorption, buccal bone expansion, tooth fractures, and retained roots. RESULTS:
      All cases and 77 (76%) controls had periodontitis; differences in extent and
      severity of periodontitis were significant, with semigeneralized or generalized
      and moderate or severe periodontitis in 78 (77%) and 93 (92%) cases,
      respectively, and 28 (28%) and 38 (38%) controls, respectively. The pattern of
      alveolar bone loss in cases was dominated by horizontal bone loss, with a
      nonsignificant increase in vertical bone loss, compared with that of controls.
      Cases were more likely than controls to have external inflammatory root
      resorption (49 [49%] vs 25 [25%]) and retained roots (57 [56%] vs 28 [28%]).
      Fewer dental fractures occurred in cases (14 [14%]) than in controls (35 [35%]).
      There were no differences between cases and controls in breed, sex, or presence
      of feline resorptive lesions or buccal bone expansion. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that FCGS was associated with more widely
      distributed and severe periodontitis, with a higher prevalence of external
      inflammatory root resorption and retained roots than other oral diseases. Full
      mouth radiographic views are indicated for cats with FCGS to diagnose the extent
      of associated periodontitis, reveal external inflammatory root resorption, and
      identify retained roots.

PMID- 24432967
TI  - Compartment syndrome associated with expansile antebrachial tumors in two dogs.
AB  - CASE DESCRIPTION: A 10-year-old spayed female Jack Russell Terrier and a 7-year
      old neutered male mixed-breed dog were evaluated because of acute, progressive,
      unilateral forelimb lameness associated with signs of pain and turgid
      antebrachial swelling. CLINICAL FINDINGS: For either dog, there were no salient
      pathological or diagnostic imaging abnormalities. A diagnosis of compartment
      syndrome was confirmed on the basis of high caudal antebrachial compartmental
      pressure in the affected forelimb. TREATMENT AND OUTCOME: Both dogs underwent
      surgical exploration of the affected forelimb. In each case, an intramuscular
      tumor (mast cell tumor in the Jack Russell Terrier and suspected sarcoma in the
      mixed-breed dog) was detected and presumed to be the cause of the high
      compartmental pressure. At 6 months following tumor excision, the dog with the
      mast cell tumor did not have any clinical signs of disease. The dog with a
      suspected sarcoma underwent tumor excision and forelimb amputation at the
      proximal portion of the humerus followed by chemotherapy; the dog was euthanized
      approximately 1 year following treatment because of pulmonary metastasis.
      CLINICAL RELEVANCE: Compartment syndrome is a serious but rarely reported
      condition in dogs and is typically ascribed to intracompartmental hemorrhage.
      These 2 cases illustrate the potential for expansile intramuscular antebrachial
      tumors to cause compartment syndrome in dogs.

PMID- 24432968
TI  - Use of pooled protozoal cultures of preputial scraping samples obtained from
      bulls for the detection of Tritrichomonas foetus by means of a real-time
      polymerase chain reaction assay.
AB  - OBJECTIVE: To determine the sensitivity of a real-time PCR assay for the
      detection of Tritrichomonas foetus in protozoal cultures of preputial scraping
      samples pooled from up to 25 bulls and to determine the specificity of that assay
      for detection of T foetus in cultures for individual animals. DESIGN: Cross
      sectional study. ANIMALS: 188 bulls and 150 steers. PROCEDURES: Preputial
      scraping samples were collected, placed in a culture kit, and incubated at 37
      degrees C for 7 days. Cultures for individual animals were tested for T foetus by
      means of a real-time PCR assay. Pools of protozoal cultures were made by
      including fixed aliquots of samples with known positive and negative results in
      ratios of 1:2, 1:3, 1:5, 1:10, 1:15, 1:20, and 1:25. Specificities of the real
      time PCR assay and culture for detection of T foetus in samples obtained from
      individual animals and sensitivity of real-time PCR assay for each evaluated pool
      ratio were determined. RESULTS: Specificity estimates for culture and the real
      time PCR assay for detection of T foetus in preputial scraping samples for
      individual animals were not significantly different (98.8% and 100%,
      respectively). Sensitivities of the real-time PCR assay for the various pooled
      samples with known positive and negative T foetus results were not significantly
      different; overall sensitivity of the assay was 94%. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated the evaluated real-time PCR assay had high
      specificity and good sensitivity for the detection of T foetus in pooled
      protozoal cultures of preputial scraping samples obtained from up to 25 animals.

PMID- 24432969
TI  - Relationships among video gaming proficiency and spatial orientation,
      laparoscopic, and traditional surgical skills of third-year veterinary students.
AB  - OBJECTIVE: To determine the relationships among traditional and laparoscopic
      surgical skills, spatial analysis skills, and video gaming proficiency of third
      year veterinary students. DESIGN: Prospective, randomized, controlled study.
      SAMPLE: A convenience sample of 29 third-year veterinary students. PROCEDURES:
      The students had completed basic surgical skills training with inanimate objects
      but had no experience with soft tissue, orthopedic, or laparoscopic surgery; the
      spatial analysis test; or the video games that were used in the study. Scores for
      traditional surgical, laparoscopic, spatial analysis, and video gaming skills
      were determined, and associations among these were analyzed by means of
      Spearman's rank order correlation coefficient (rs). RESULTS: A significant
      positive association (rs = 0.40) was detected between summary scores for video
      game performance and laparoscopic skills, but not between video game performance
      and traditional surgical skills scores. Spatial analysis scores were positively
      (rs = 0.30) associated with video game performance scores; however, that result
      was not significant. Spatial analysis scores were not significantly associated
      with laparoscopic surgical skills scores. Traditional surgical skills scores were
      not significantly associated with laparoscopic skills or spatial analysis scores.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated video game
      performance of third-year veterinary students was predictive of laparoscopic but
      not traditional surgical skills, suggesting that laparoscopic performance may be
      improved with video gaming experience. Additional studies would be required to
      identify methods for improvement of traditional surgical skills.

PMID- 24432970
TI  - Single-incision laparoscopic sleeve gastrectomy versus multiport laparoscopic
      sleeve gastrectomy: analysis of 80 cases in a single center.
AB  - BACKGROUND: Through efficacy and improved safety, multiport laparoscopic sleeve
      gastrectomy (LAPS-G) has emerged as an important and broadly available treatment
      option for people with severe and complex obesity. Because a single-incision
      laparoscopic sleeve gastrectomy (SILS-G) would be less invasive, we applied this
      novel surgical technique for a selected number of patients enrolled into our
      minimally invasive bariatric program. SUBJECTS AND METHODS: A retrospective
      review of prospectively collected data from 80 morbidly obese patients who
      qualified for SILS-G or LAPS-G was performed from January 2011 to May 2012.
      RESULTS: SILS-G and LAPS-G were performed in 40 patients, respectively. All
      patients were female. Mean age was 41 (range, 19-73) years (SILS-G, 37 [19-62]
      years; LAPS-G, 43 [24-73] years; P=not significant). Preoperative body mass index
      was 40.8 (35.1-45.0) kg/m(2) in the SILS-G group and 43.8 (35.0-47.8) kg/m(2) in
      the LAPS-G group (P=not significant). Total operative time was significantly
      lower in the SILS-G group (85+/-21 minutes) compared with the LAPS-G group (97+/
      26 minutes) (P<.05). Median percentage excess weight loss was comparable in both
      groups (SILS-G, 57.2%; LAPS-G, 53.7%) at 6.6 months after surgery. Mean hospital
      stay was 5 days (SILS-G, 5 [4-24] days; LAPS-G, 6 [4-14] days; P=not
      significant). Complication rates were low in both groups: leakage, 2.5% in SILS-G
      and 0% in LAPS-G; bleeding, 2.5% in SILS-G and 2.5% in LAPS-G; and trocar-site
      hernia, 0% in both groups. Patients operated on with single-incision laparoscopy
      had a significantly better cosmetic outcome as assessed by a scar satisfaction
      assessment questionnaire (P<.01). CONCLUSIONS: SILS-G is a feasible and safe
      operative procedure that leads to a significant reduction of total operative time
      compared with a multiport access procedure. Further potential benefits associated
      with single-incision laparoscopic surgery remain to be investigated objectively.

PMID- 24432973
TI  - Self-assembly of faceted particles triggered by a moving ice front.
AB  - The possibility to align and organize faceted particles in the bulk offers
      intriguing possibilities for the design and discovery of materials and
      architectures exhibiting novel functional properties. The growth of ice crystals
      can be used to trigger the self-assembly of large, anisotropic particles and
      consequently to obtain three-dimensional porous materials of large dimensions in
      a limited amount of time. These mechanisms have not been explored so far due to
      the difficulty to experimentally investigate these systems. Here we elucidate the
      self-assembly mechanisms of faceted particles driven by ice growth by a
      combination of X-ray holotomography and discrete element modeling, providing
      insights into both the dynamics of self-assembly and their final packing. The
      encapsulation of particles is the result of a delicate balance between the force
      exerted by the percolating network of concentrated particles and the force
      exerted by the moving interface. We illustrate the benefits of such self-assembly
      for thermal management composite materials. 

PMID- 24432974
TI  - Gd3N@C84(OH)x: a new egg-shaped metallofullerene magnetic resonance imaging
      contrast agent.
AB  - Water-soluble derivatives of gadolinium-containing metallofullerenes have been
      considered to be excellent candidates for new magnetic resonance imaging (MRI)
      contrast agents because of their high relaxivity and characteristic encapsulation
      of the lanthanide ions (Gd(3+)), preventing their release into the
      bioenvironment. The trimetallic nitride template endohedral metallofullerenes
      (TNT EMFs) have further advantages of high stability, high relative yield, and
      encapsulation of three Gd(3+) ions per molecule as illustrated by the previously
      reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the
      preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a
      pentalene (fused pentagons) motif and an egg-shaped structure. The Gd3N@C84
      derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80
      derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high
      (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl
      content and aggregate size, as confirmed by X-ray photoelectron spectroscopy
      (XPS) and dynamic light scattering (DLS) experiments, which could be the main
      reasons for the higher relaxivity.

PMID- 24432976
TI  - Magnetic catechin-dextran conjugate as targeted therapeutic for pancreatic tumour
      cells.
AB  - BACKGROUND: Catechin-dextran conjugates have recently attracted a lot of
      attention due to their anticancer activity against a range of cancer cells.
      Magnetic nanoparticles have the ability to concentrate therapeutically important
      drugs due to their magnetic-spatial control and provide opportunities for
      targeted drug delivery. PURPOSE: Enhancement of the anticancer efficiency of
      catechin-dextran conjugate by functionalisation with magnetic iron oxide
      nanoparticles. METHODS: Modification of the coating shell of commercial magnetic
      nanoparticles (Endorem) composed of dextran with the catechin-dextran conjugate.
      RESULTS: Catechin-dextran conjugated with Endorem (Endo-Cat) increased the
      intracellular concentration of the drug and it induced apoptosis in 98% of
      pancreatic tumour cells placed under magnetic field. DISCUSSION: The conjugation
      of catechin-dextran with Endorem enhances the anticancer activity of this drug
      and provides a new strategy for targeted drug delivery on tumour cells driven by
      magnetic field. CONCLUSION: The ability to spatially control the delivery of the
      catechin-dextran by magnetic field makes it a promising agent for further
      application in cancer therapy.

PMID- 24432979
TI  - Novel inhibitors of signal transducer and activator of transcription 3 signaling
      pathway: an update on the recent patent literature.
AB  - INTRODUCTION: The signal transducer and activator of transcription 3 (STAT3) is a
      transcription factor that plays a key role in normal cell growth and is
      constitutively activated in about 70% of solid and hematological cancers. Thus,
      the development of potent and selective inhibitors that target STAT3 is of
      interest especially in the cancer therapeutic area. AREAS COVERED: This review
      updates new patents claiming STAT3 inhibitors and their uses published from 2011
      to 2013. Pre-2011 patents have been extensively covered in previous reviews.
      Comments on the context of each chemical series are given where applicable to
      orientate the readers on the bewildering array of molecular designs now
      available. EXPERT OPINION: The growing number of preclinical studies in numerous
      malignances as well as the first clinical trials of STAT3 inhibitors suggest that
      STAT3 remains a valid target for the treatment of human cancers as well as
      inflammatory diseases and/or autoimmune disorders. So, the future looks bright
      for patients because many new drugs are being developed and now combinations of
      STAT3 inhibitors with other targeted agents can diminish the resistance to
      traditional chemotherapy. These advances are expected to lead to further
      significant progress improving patient outcomes and quality of life.

PMID- 24432980
TI  - Characterization of starch polymorphic structures using vibrational sum frequency
      generation spectroscopy.
AB  - The polymorphic structures of starch were characterized with vibrational sum
      frequency generation (SFG) spectroscopy. The noncentrosymmetry requirement of SFG
      spectroscopy allows for the detection of the ordered domains without spectral
      interferences from the amorphous phase and also the distinction of the symmetric
      elements among crystalline polymorphs. The V-type amylose was SFG-inactive due to
      the antiparallel packing of single helices in crystal unit cells, whereas the A-
      and B-type starches showed strong SFG peaks at 2904 cm(-1) and 2952-2968 cm(-1),
      which were assigned to CH stretching of the axial methine group in the ring and
      CH2 stretching of the exocyclic CH2OH side group, respectively. The CH2/CH
      intensity ratios of the A- and B-type starches are significantly different,
      indicating that the conformation of hydroxymethyl groups in these two polymorphs
      may be different. Cyclodextrin inclusion complexes were also analyzed as a
      comparison to the V-type amylose and showed that the head-to-tail and head-to
      head stacking patterns of cyclodextrin molecules govern their SFG signals and
      peak positions. Although the molecular packing is different between V-type
      amylose and cyclodextrin inclusion complexes, both crystals show the annihilation
      of SFG signals when the functional group dipoles are arranged pointing in
      opposite directions. 

PMID- 24432981
TI  - Quantification of a botanical negative marker without an identical standard:
      ginkgotoxin in Ginkgo biloba.
AB  - A new strategy for the analysis of natural products uses a combination of
      quantitative (1)H NMR (qHNMR) and adsorbent-free countercurrent separation (CS)
      methodology to establish a quantification method for ginkgotoxin (4'-O
      methylpyridoxine) in Ginkgo biloba preparations. The target analyte was
      concentrated in a one-step CS process using the ChMWat +2 solvent system (CHCl3
      MeOH-H2O, 10:5:5) and subsequently assayed by qHNMR. While commercial G. biloba
      seeds contained 59 MUg of ginkgotoxin per seed, the compound was below the limit
      of detection (9 ppm) in a typical leaf extract. Due to the enrichment potential
      and loss-free operation of CS, the combination of CS and qHNMR is a generally
      suitable approach for threshold assays aimed at quantifying target compounds such
      as botanical negative markers at the low ppm level. As the proof of principle is
      demonstrated for relatively small CS capacities (20 mL, 1:40 loading) and modest
      NMR sensitivity (n = 16, 400 MHz, 5 mm RT probe), the approach can be adapted to
      quantification at the ppb level. The procedure enables the quantification of a
      botanical negative marker in the absence of identical reference material, which
      otherwise is a prerequisite for LC-based assays. 

PMID- 24432984
TI  - Estimated glomerular filtration rate is associated with both arterial stiffness
      and N-terminal pro-brain natriuretic peptide in newly diagnosed hypertensive
      patients.
AB  - Even a slight decrease in the glomerular filtration rate (GFR) is an independent
      risk factor for cardiovascular disease. Arterial stiffness, left ventricular
      hypertrophy and N-terminal pro-brain natriuretic peptide (NT-proBNP) are
      independent risk factors for cardiovascular disease, which are particularly
      common in end-stage renal disease. We aimed to evaluate the association between
      GFR with arterial stiffness, left ventricle mass (LVM) and NT-proBNP in
      hypertensive subjects with normal to mildly impaired renal function. The study
      population consisted of 285 newly diagnosed hypertensive patients (mean age; 49.9
      +/- 11.8 years). GFR was estimated (eGFR) by the Modification of Diet in Renal
      Disease formula. Pulse wave velocity (PWV) and augmentation index (AIx), which
      reflects arterial stiffness, were calculated using the single-point method via
      the Mobil-O-Graph(r) ARCsolver algorithm. LVM was obtained by echocardiography.
      Plasma NT-proBNP was measured by electrochemiluminescence. The patients were
      divided into two groups according to the median eGFR value (eGFRlow group <101
      ml/min/1.73 m(2) and eGFRhigh group >= 101 ml/min/1.73 m(2)). LVM and NT-proBNP
      values were higher in eGFRlow group compared with eGFRhigh group (p<0.05). Pulse
      wave velocity and augmentation index values were higher in eGFRlow group compared
      with eGFRhigh group (p<0.05, for all). Multiple linear regression analysis showed
      that eGFR was independently associated with PWV (beta=-0.422, p<0.001) and NT
      proBNP (beta=-0.404, p<0.001). Present study showed that eGFR was independently
      associated with PWV and NT-proBNP values. Importantly, these findings may
      explain, in part, the increase in cardiovascular risk in with slightly impaired
      renal function.

PMID- 24432985
TI  - 1,3-Cationic alkylidene migration of nonclassical carbocation: a density
      functional theory study on gold(I)-catalyzed cycloisomerization of 1,5-enynes
      containing cyclopropene moiety.
AB  - For quite a long time, nonclassical carbocations have only been regarded as
      special intermediates with limited cases in solvolysis reactions. However, the
      present work shows that in common reaction, typical nonclassical carbocations may
      be involved in and have significant effects on the reaction mechanisms. In this
      work, DFT studies have been performed on the mechanism of gold(I)-catalyzed
      cycloisomerization of 1,5-enynes containing cyclopropene moiety at PBE1PBE/6
      31+G**/SDD level. An unprecedented pathway containing two consecutive 1,3
      cationic alkylidene migrations of nonclassical carbocation intermediates derived
      from norbornenyl cation, rather than the generally considered Wagner-Meerwein 1,2
      alkyl migrations, was found. Detailed structural analysis shows the nature of
      this 1,3-cationic alkylidene migration: it is promoted by strong cation-pi
      interaction between the cationic center and the double bond. Topological analysis
      shows that for certain nonclassical carbocation intermediates (1c'-A and 1c'-F),
      there do exist bond critical point and bond path between the cationic center and
      the double bond. On the basis of the mechanisms proposed, the product selectivity
      controlled by the substituent effects was also rationalized. 

PMID- 24432986
TI  - Slowly Progressive Keratouveitis in a Patient with Known Systemic Leishmaniasis
      and HIV.

PMID- 24432988
TI  - Hypermethylation of a New Distal Sodium/Iodide Symporter (NIS) enhancer (NDE) is
      associated with reduced NIS expression in thyroid tumors.
AB  - CONTEXT: In thyroid tumors, reduced radioiodine uptake is associated with worse
      patient outcome concomitantly with low sodium/iodide symporter (NIS) mRNA
      expression. Previous studies showed that CpG-island methylation in the NIS
      proximal promoter does not correlate with mRNA expression. OBJECTIVES: The aim of
      the study was to identify new CpG-islands within the NIS 5'region and investigate
      the involvement of their methylation in NIS expression. DESIGN: DNA was obtained
      from 30 pairs of thyroid samples: tumor (T) and surrounding nontumor (NT)
      samples. All T samples had reduced NIS mRNA expression compared to NT samples.
      MAIN OUTCOME MEASURES: Methylation degree was quantified by bisulfite sequencing,
      and NIS expression by real-time PCR and Western blot. Reporter gene assays were
      performed to determine CpG-island functionality. Tumor cell cultures were treated
      with 5-Aza demethylating agent to determine NIS expression, methylation status,
      and (125)I uptake. RESULTS: We identified a new CpG-island2 with 14 CpG sites,
      located -2152/-1887 relative to ATG site. CpG-island2 was hypermethylated in T
      compared to NT samples, in both benign and malignant tumor groups. There was a
      significant inverse correlation between NIS mRNA expression and degree of CpG
      island2 methylation in NT and T samples. This sequence increased the expression
      of a reporter gene; thus, it was considered a new enhancer. Cell culture
      treatments with 5-Aza reduced CpG-island2 methylation levels concomitantly with
      restoration of NIS mRNA and protein expression and (125)I uptake. CONCLUSIONS: We
      identified a new distal enhancer, NIS distal enhancer, that regulates gene
      expression through DNA methylation. This enhancer is hypermethylated in T
      compared to NT samples and is associated with decreased NIS expression in tumors.
      This epigenetic deregulation may be an early event in tumorigenesis.

PMID- 24432989
TI  - Increased placental expression of fibroblast growth factor 21 in gestational
      diabetes mellitus.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF21) can regulate glucose and lipid
      metabolism. The placenta actively synthesizes and secretes many hormones, but it
      is unknown whether this includes FGF21. This study aimed to analyze the placental
      expression of FGF21 in women with or without gestational diabetes mellitus (GDM).
      METHODS: FGF21 and peroxisome proliferator-activated receptor (PPAR)-alpha mRNA
      and protein expression were measured in the placentae of 20 women with and 18
      without GDM. mRNA expression of PPARalpha, FGF receptors 1-4, the coreceptor beta
      klotho, and glucose transporter (GLUT)-1, -3, and -4 was investigated. Maternal
      and fetal circulating FGF21 levels were assessed in 10 mother-baby dyads per
      condition. RESULTS: FGF21 was expressed in the placenta and its mRNA expression
      increased in women with GDM [10.75 (interquartile range 3.28-125.6 AU)] vs
      control [0.83 (0.22-4.78), P < .001], as is its protein expression [GDM 2.89
      (1.44-5.10)] vs control [0.42 (0.05-1.98), P < .05]. PPARalpha mRNA but not
      protein expression was increased in GDM [2.94 (0.70-7.26)] vs control [0.99 (0.43
      2.17), P < .05] and was positively correlated to FGF21 mRNA expression (rho =
      0.43, P < .01). Placental mRNA expression of FGF receptors and GLUT1 was
      unchanged, and beta-klotho, GLUT3, and GLUT4 showed increased expression in GDM.
      Maternal circulating FGF21 levels were similar [GDM 323 (75-921) vs control 269
      (49-731) pg/mL, P = .81]. FGF21 was undetected in fetal cord blood. CONCLUSIONS:
      FGF21 is expressed in the placenta and its expression is increased in GDM. The
      absence of FGF21 in fetal cord blood suggests that neither placental FGF21 nor
      maternal circulating FGF21 is secreted into the fetal circulation. Placental
      FGF21 may be a regulator of placental metabolism.

PMID- 24432990
TI  - Estrone sulfate source of estrone and estradiol formation in isolated human hair
      roots: identification of a pathway linked to hair growth phase and subject to
      site-, gender-, and age-related modulations.
AB  - BACKGROUND: The present study investigated the metabolism of estrone sulfate into
      bioactive estrogens in the human hair root, including the effects of hair growth
      phase, anatomical site, gender, and age. METHODS: Healthy male (n = 18) and
      female (n = 20) subjects were investigated. Growing (anagen) and resting
      (telogen) hair roots were collected from selected scalp and body sites. RESULTS:
      Estrone sulfate metabolism in the hair root yielded substantial levels of estrone
      and estradiol. Estrogen synthesis exceeded that associated with aromatization of
      androgens in a previous study. In subjects <50 years old, estrogen synthesis in
      scalp hair was lower in men than in women. Comparable levels of estrogen
      formation were observed in 1) male and female axillary and pubic hair and 2) male
      beard hair. These levels were higher than the estrogen levels detected in the in
      scalp hair of men <50 years old. With increasing age, estrogen synthesis
      increased in men and decreased in women. In telogen hair from all body sites, the
      capacity to form estrone from estrone sulfate remained unaffected, whereas the
      ability to form estradiol decreased by 62% and 86% in men and women,
      respectively. CONCLUSIONS: Estrogen formation from estrone sulfate in sexually
      dimorphic hair is linked to the hair growth phase and is subject to gender- and
      age-related modulations. The magnitude of the in situ estrogen synthesis from
      estrone sulfate and the selective arrest of estradiol synthesis at the end of the
      hair cycle suggest that this pathway plays a crucial role in the regulation of
      human hair growth.

PMID- 24432991
TI  - A novel ADIPOQ mutation (p.M40K) impairs assembly of high-molecular-weight
      adiponectin and is associated with early-onset obesity and metabolic syndrome.
AB  - CONTEXT: The phenotypic effects of ADIPOQ mutations early in life, prior to type
      2 diabetes onset, have not been studied. AIM: The objective of the study was to
      characterize the impact of a novel ADIPOQ mutation in vitro and in vivo. DESIGN:
      The design of the study was ADIPOQ screening, adiponectin oligomerization, and
      cardiometabolic phenotype assessment. SUBJECTS: Fourteen hypoadiponectinemic (<3
      MUg/mL) and 686 normoadiponectinemic young adults (23-25 y) were prospectively
      followed up since birth. MAIN OUTCOME MEASURES: Human and recombinant murine
      mutant adiponectin oligomerization, the proband's ADIPOQ and ADIPOR1/R2 adipose
      tissue (AT) expression, and cardiometabolic profile were measured. RESULTS: The
      heterozygous ADIPOQ p.M40K mutation was identified in one hypoadiponectinemic
      male (2.4 MUg/mL) and three other family members. Carriers presented a marked
      reduction of serum high-molecular weight to total adiponectin ratio when compared
      with controls (9.4% +/- 1% vs 56.6% +/- 13%; P < .05) and family noncarriers
      (9.4% +/- 1% vs 42% +/- 0.5%; P = .05). Both mRNA and protein levels of
      adiponectin were increased in the AT of the proband (2.3- and 1.6-fold,
      respectively). However, the high-molecular weight to total adiponectin ratio of
      adiponectin was decreased (3.3-fold). Moreover, the expressions of ADIPOR1 and
      ADIPOR2 were significantly down-regulated in the AT of the proband (6- and 1.2
      fold, respectively). The results were confirmed by in vitro studies on the
      recombinant murine homologous mutation (p.M43K). The proband's cardiometabolic
      phenotype progression was further characterized: born small for gestational age
      and adolescence-onset obesity; insulin resistance (homeostasis assessment model
      of insulin resistance of 4.7), and dyslipidemia at 25 years; decreased high
      molecular weight adiponectin (0.24 MUg/mL = 10%), hypertension (180/120 mm Hg),
      steatosis (fat liver = 40% +/- 6%), increased carotid intima-media thickness at
      31 years, and type 2 diabetes (glycosylated hemoglobin = 6.6%) at 34 years of
      age. Of note, all of the affected family members presented features of metabolic
      syndrome. CONCLUSION: The newly identified ADIPOQ p.M40K mutation associates with
      severe cardiometabolic dysfunction due to the impairment of high-molecular weight
      adiponectin complex formation.

PMID- 24432992
TI  - Radioiodine ablation of postsurgical thyroid remnants after treatment with
      recombinant human TSH (rhTSH) in patients with moderate-to-severe graves'
      orbitopathy (GO): a prospective, randomized, single-blind clinical trial.
AB  - CONTEXT: Recent evidence suggests thyroidectomy (Tx) followed by radioiodine
      remnant ablation to be beneficial to Graves' orbitopathy (GO) patients.
      OBJECTIVE: The aim of the study was to evaluate the effect of (131)I thyroid
      ablation after recombinant human TSH stimulation in patients with moderate-to
      severe GO. DESIGN, PATIENTS, AND INTERVENTIONS: The study was prospective,
      randomized, and single-blind, and it included 40 consecutive patients with
      moderate-to-severe GO randomized into: 1) a Tx-radioactive iodine (RAI) group (20
      subjects who underwent total-Tx and (131)I ablation after recombinant human TSH
      stimulation); and 2) a Tx group (20 subjects who underwent total-Tx alone).
      OUTCOME MEASURES: The overall GO outcome 12 months after Tx/radioiodine ablation
      was the main measure. RESULTS: GO evaluation at the end of iv glucocorticoids
      showed eye disease to be improved in 65% of the Tx-RAI group and 60% of the Tx
      group patients. At 6 and 12 months, no further changes in the GO outcome could be
      observed in the Tx-RAI group. Conversely, five patients from the Tx group
      exhibited a deterioration in GO. At 12 months, GO was found to be improved in 70%
      of the Tx-RAI and 20% of the Tx group patients, the latter being found to be
      stable (55%) or worse (25%) than at baseline evaluation. At 12 months, GO was
      found to be inactive in a significantly higher percentage of patients in the Tx
      RAI than in the Tx group (75 vs 30%; P < .01). CONCLUSIONS: Postoperative
      radioiodine ablation proved more effective than Tx alone in inducing earlier and
      steadier GO improvement in patients with moderate-to-severe GO treated with iv
      glucocorticoids over a 24-month follow-up period.

PMID- 24432993
TI  - Persistent mucosal damage and risk of fracture in celiac disease.
AB  - CONTEXT: Celiac disease (CD) is associated with an increased fracture risk, an
      increase that persists after diagnosis. A significant proportion of patients with
      CD have persistent villous atrophy (VA) on follow-up biopsy. OBJECTIVE: The
      objective of the study was to determine whether persistent VA impacts long-term
      fracture risk. DESIGN: This was a cohort study. SETTING AND PATIENTS: We
      identified all patients in Sweden with histological evidence of CD who underwent
      a follow-up biopsy and compared patients with persistent VA with those with
      mucosal healing. MAIN OUTCOME MEASURES: The following were measured: 1) any
      fracture; 2) likely osteoporotic fracture (defined as fractures of the hip,
      distal forearm, thoracic and lumbar spine, or proximal humerus); and 3) hip
      fracture. RESULTS: Of 7146 patients, VA was present on follow-up biopsy in 43%.
      There was no significant association between persistent VA and overall fractures
      [hazard ratio (HR) of persistent VA compared with those with healing 0.93, 95%
      confidence interval (CI) 0.82-1.06] or with likely osteoporotic fractures (HR
      1.11, 95% CI 0.84-1.46). Persistent VA was associated with an increased risk of
      hip fracture (HR 1.67, 95% CI 1.05-2.66). Hip fracture risk increased, depending
      on the degree of VA (HR for partial VA compared with those with healing 1.70, 95%
      CI 0.82-3.49, HR for subtotal/total VA compared with those with healing 2.16, 95%
      CI 1.06-4.41). CONCLUSIONS: Persistent VA on follow-up biopsy is predictive of
      hip fracture risk. The association between persistent VA and hip fractures, but
      not fractures overall, implies that thinner sc tissue and fall or trauma may be
      mechanisms by which persistent VA confers an increased fracture risk.

PMID- 24432994
TI  - Glucose effectiveness in nondiabetic relatives: dysglycemia and beta-cell
      function at 10 years.
AB  - AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in
      individuals with a family history of type 2 diabetes. We examined retrospectively
      at 10 years in normoglycemic relatives of diabetic subjects (RELs) the
      pathophysiological role of glucose effectiveness in the development of isolated
      impaired fasting glucose, glucose intolerance, and acute insulin release.
      METHODS: At 0 years, 19 RELs and 18 matched control subjects had glucose
      effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and
      disposition index measured during an iv glucose tolerance test (IVGTT), using the
      minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and
      AIROGTT were determined. RESULTS: At 0 years, fasting glucose (FG) and GE were
      raised in RELs, but insulin sensitivity and AIROGTT were reduced (P <= .05)
      compared with controls. At 10 years, RELs developed raised fasting and 2-hour
      OGTT glucose. FG10y correlated significantly with FG0y and body mass index0y and
      negatively with ?GE and 2-hour OGTT glucose10y with FG0y and negatively with
      AIRIVGTT0y and AIROGTT0y. Log AIROGTT10y correlated with ?GE, log AIRIVGTT0y and
      log AIROGTT0y. Multiple regression analyses demonstrated the following: REL FG10y
      was predicted by combined FG0y, ?GE and body mass index0y (radj(2) = 56%; P <=
      .001) and 2-hour OGTT glucose10y weakly related by FG0y,and ?GE (r(adj)(2) = 25%;
      P = .06). Log AIROGTT10y was predicted by AIRIVGTT0y and ?GE (r(adj)(2) = 46%; P
      <= .004). CONCLUSION: In normoglycemic RELs, a relative reduction of glucose
      effectiveness is an important contributor over 10 years to the development of
      isolated impaired fasting glucose and reduced acute insulin secretion.

PMID- 24432995
TI  - Chinese herbal medicine Tianqi reduces progression from impaired glucose
      tolerance to diabetes: a double-blind, randomized, placebo-controlled,
      multicenter trial.
AB  - CONTEXT: Living in a prediabetes state significantly increases a patient's risk
      for both diabetes and cardiovascular disease. Tianqi capsule, containing 10
      Chinese herbal medicines, is used in China for the treatment of type 2 diabetes
      mellitus (T2DM). OBJECTIVE: The purpose of this study was to assess whether
      Tianqi prevented T2DM in subjects with impaired glucose tolerance (IGT) over the
      course of a 12-month treatment. METHODS: Individuals with IGT were randomly
      allocated in a double-blind manner to receive Tianqi (n = 210) or a placebo (n =
      210) for 12 months. Oral glucose tolerance tests were conducted every 3 months to
      assess the development of diabetes or restoration to normal glucose tolerance.
      All subjects received the same lifestyle education. The primary endpoint was the
      conversion of IGT to T2DM. Body weight and body mass index were observed. Adverse
      effects were monitored. RESULTS: Of the 420 enrolled subjects with IGT, 389
      completed the trial (198 in the Tianqi group and 191 in the placebo group). At
      the end of the 12-month trial, 36 subjects in the Tianqi group (18.18%) and 56 in
      the placebo group (29.32%) had developed diabetes (P = .01). There was a
      significant difference in the number of subjects who had normal glucose tolerance
      at the end of the study between the Tianqi and placebo groups (n = 125, 63.13%,
      and n = 89, 46.60%, respectively; P = .001). Cox's proportional hazards model
      analysis showed that Tianqi reduced the risk of diabetes by 32.1% compared with
      the placebo. No severe adverse events occurred in the trial. There were no
      statistical differences in body weight and body mass index changes between the
      Tianqi group and the placebo group during the 12-month trial. CONCLUSIONS:
      Treatment with a Tianqi capsule for 12 months significantly decreased the
      incidence of T2DM in subjects with IGT, and this herbal drug was safe to use.

PMID- 24432997
TI  - WITHDRAWN: Low-density lipoprotein cholesterol is associated with fracture risk
      in diabetes patients - a nested case-control study.
AB  - AIM: Diabetes Mellitus is associated with an increased risk of fractures, which
      is not explained fully by bone mineral density and common risk factors. The aim
      of this study is to investigate the association of medication and biochemical
      markers on the risk of fracture in a diabetes population. METHODS: Nested case
      control study based on Danish diabetes patients from The Danish National Hospital
      Discharge Registry. The cases of the study were diabetes patients with a fracture
      (n= 24,349) and controls were diabetes patients with no fracture (n=132,349). A
      total of 2,816 diabetes patients were available for an analysis of patient
      characteristics, co-morbidities, biochemical parameters and drug usage. RESULTS:
      Patient age at the time of diabetes diagnosis, a diagnosis of previous fracture,
      an alcohol related diagnosis, total cholesterol level, and the usage of
      antidepressants, antiepileptics and insulin all increased the odds of fracture.
      Low-density lipoprotein cholesterol (LDL) levels decreased the odds of fracture,
      where the level of 3.04-5.96 mmol/l was optimal with regard to fracture risk.
      CONCLUSION: LDL may add to the understanding of fractures in diabetes patients
      and it may be added to current fracture risk models in diabetes patients.

PMID- 24432996
TI  - Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and
      do not change with intensification of insulin.
AB  - CONTEXT: Bile acids (BAs) are newly recognized signaling molecules in glucose and
      energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus
      (T2D) remain incompletely understood. OBJECTIVE: The objective of the study was
      to assess serum BA composition in impaired glucose-tolerant, T2D, and normal
      glucose-tolerant persons and to monitor the effects of improving glycemia on
      serum BA composition in T2D patients. DESIGN AND SETTING: This was a cross
      sectional cohort study in a general population (cohort 1) and nonrandomized
      intervention (cohort 2). PATIENTS AND INTERVENTIONS: Ninety-nine volunteers
      underwent oral glucose tolerance testing, and 12 persons with T2D and
      hyperglycemia underwent 8 weeks of intensification of treatment. MAIN OUTCOME
      MEASURES: Serum free BA and respective taurine and glycine conjugates were
      measured by HPLC tandem mass spectrometry. RESULTS: Oral glucose tolerance
      testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons.
      Concentrations of total taurine-conjugated BA were higher in T2D and intermediate
      in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate
      regression revealed a positive association between total taurine-BA and fasting
      glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin
      A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic
      model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse
      association with oral disposition index (R = -0.36, P < .001). Insulin-mediated
      glycemic improvement in T2D patients did not change fasting serum total BA or BA
      composition. CONCLUSION: Fasting taurine-conjugated BA concentrations are higher
      in T2D and intermediate in impaired compared with normal glucose-tolerant persons
      and are associated with fasting and postload glucose. Serum BAs are not altered
      in T2D in response to improved glycemia. Further study may elucidate whether this
      pattern of taurine-BA conjugation can be targeted to provide novel therapeutic
      approaches to treat T2D.

PMID- 24432998
TI  - Subclinical hypothyroidism, weight change, and body composition in the elderly:
      the Cardiovascular Health Study.
AB  - BACKGROUND: Subclinical hypothyroidism is common in the elderly, yet its
      relationship with weight and body composition is unclear. OBJECTIVE: We examined
      the relationship between subclinical hypothyroidism and weight change and body
      composition in older adults. METHODS: A total of 427 subclinically hypothyroid
      and 2864 euthyroid U.S. individuals >=65 years old enrolled in the Cardiovascular
      Health Study and not taking thyroid preparations were included. Analyses of 6
      year weight change were performed, compared by thyroid status. A cross-sectional
      analysis of thyroid status and body composition was performed in a subset of 1276
      participants who had dual-energy x-ray absorptiometry scans. Models were risk
      factor-adjusted and stratified by sex. RESULTS: Overall, participants lost weight
      during follow-up (-0.38 kg/y in men, -0.37 kg/y in women). Subclinical
      hypothyroidism, when assessed at a single time point or persisting over 2 years,
      was not associated with a difference in weight change compared with euthyroidism.
      Subclinical hypothyroidism was also not associated with differences in lean mass,
      fat mass, or percent fat compared with euthyroidism. A TSH level 1 mU/L higher
      within the euthyroid or subclinical hypothyroid range was associated with a 0.51
      kg higher baseline weight in women only (P < .001) but not with weight change in
      either sex. A 1 ng/dL higher free T4 level was associated with lower baseline
      weight and 0.32 kg/y greater weight loss in women only (P = .003). Baseline
      weight and weight change did not differ by T3 levels. CONCLUSIONS: Our data do
      not support a clinically significant impact of subclinical hypothyroidism on
      weight status in the elderly.

PMID- 24432999
TI  - Dipeptidyl peptidase 4 inhibitor sitagliptin maintains beta-cell function in
      patients with recent-onset latent autoimmune diabetes in adults: one year
      prospective study.
AB  - CONTEXT: Dipeptidyl peptidase 4 (DPP-4) inhibitors have been widely used in type
      2 diabetes. An important unanswered question concerns the effect of DPP-4
      inhibition on beta-cell function in patients with autoimmune diabetes. OBJECTIVE:
      The objective of the study was to investigate the effects of the DPP-4 inhibitor
      on beta-cell function in patients with recent-onset latent autoimmune diabetes in
      adults (LADA). DESIGN AND SETTING: This study was an open-label, randomized
      controlled study conducted in the Department of Endocrinology at the Second
      Xiangya Hospital. PATIENTS AND INTERVENTION: Thirty recently diagnosed LADA
      patients were randomized 1:1 to receive insulin therapy with 100 mg/d sitagliptin
      (group A, n = 15) or without sitagliptin (group B, n = 15) for 12 months. MAIN
      OUTCOME MEASURES: Fasting and 2-hour postprandial blood samples were obtained at
      baseline and after 3, 6, 9, and 12 months of treatment to determine blood
      glucose, glycosylated hemoglobin, and C-peptide levels. RESULTS: There were no
      differences in the clinical baseline data between the two groups. During the 12
      months of follow-up, there were no significant differences in glucose and
      glycosylated hemoglobin levels between the two groups. At 12 months, fasting C
      peptide (FCP), 2-hour postprandial C-peptide (CP), and DeltaCP (DeltaCP = 2 h CP
      FCP) levels were not different in group A (P > .05) compared with baseline,
      whereas in group B the levels of FCP, 2-hour CP and DeltaCP were significantly
      decreased compared with baseline (P < .05). Levels of 2-hour CP were higher in
      group A than group B at 12 months (P < .05). CONCLUSIONS: LADA patients treated
      with sitagliptin and insulin maintained beta-cell function by comparison with
      insulin alone.

PMID- 24433000
TI  - Thyroglobulin suppresses thyroid-specific gene expression in cultures of normal
      but not neoplastic human thyroid follicular cells.
AB  - CONTEXT: It was shown in the rat thyroid that thyroglobulin (Tg) stored in the
      follicular lumen is a potent regulator of thyroid-specific gene expression to
      maintain the function of individual follicles. However, the actions of Tg as a
      regulatory molecule in human thyroid have not been studied. OBJECTIVE: Our
      objective was to determine the effect of Tg on gene expression in normal and
      diseased human thyroid and to examine whether the proposed model of negative
      feedback autocrine regulation of thyroid function by Tg is applicable in the
      human as well as the rat. DESIGN: Primary cultures of human thyrocytes were
      established from normal thyroid, Graves' disease thyroid, adenomatous goiter,
      follicular adenoma, and papillary carcinoma tissues obtained during surgery.
      Cells were stimulated with physiologic (ie, follicular) concentrations of Tg, and
      mRNA and protein expression of genes involved in thyroid hormonogenesis were
      evaluated. The effects of Tg on thyroid-specific gene expression were also
      assessed in 2 human papillary carcinoma cell lines. RESULTS: Transcript levels of
      genes participating in thyroid hormone biosynthesis were significantly reduced by
      Tg in thyrocyte cultures derived from normal and Graves' thyroid, but not in
      cultures derived from thyroid neoplasms and adenomatous goiter. CONCLUSION: It
      was confirmed that Tg acts as a negative-feedback regulator of gene expression in
      human thyrocytes, suggesting that Tg signaling may constitute a common mechanism
      for maintaining thyroid homeostasis in species with follicular thyroid
      morphology. However, certain diseases of intrinsic thyroid overgrowth appear to
      be associated with an escape from the regulatory mechanism of Tg.

PMID- 24433001
TI  - Denosumab treatment for juvenile Paget's disease: results from two adult patients
      with osteoprotegerin deficiency ("Balkan" mutation in the TNFRSF11B gene).
AB  - CONTEXT: Most patients with juvenile Paget's disease (JPD) have homozygous loss
      of-function mutations in the TNFRSF11B gene resulting in osteoprotegerin
      deficiency. Because recombinant osteoprotegerin is not available for clinical
      use, an alternative therapeutic approach could be denosumab, which acts on the
      same pathway. MAIN OBJECTIVE: The aim was to study the effect of denosumab on
      bone turnover markers in two adult patients with JPD ("Balkan" mutation)
      previously treated with calcitonin and bisphosphonates. SETTING: The study was
      conducted at two tertiary hospitals in Greece. PATIENTS: Patient 1 (a 36-year-old
      woman) developed a severe and long-term hypocalcemia after a single dose (3.5 mg)
      of zoledronic acid. Her bone disease remained active despite treatment. Patient 2
      (a 67-year-old man) had satisfactorily controlled bone disease with only
      intermittent risedronate treatment during the last 10 years, but suffered from
      progressive loss of hearing and vision. Low doses (20-40 mg) of denosumab every 3
      6 months were administered in both patients. RESULTS: Bone markers (including
      total and bone-specific alkaline phosphatase, procollagen I N-terminal peptide,
      and osteocalcin) were reduced to normal levels in both patients, with nadir
      observed 2-4 months after each denosumab injection. Retinal and hearing
      involvement remained unchanged, but patient 2 developed a rapid progression of
      cataract in the right eye. CONCLUSIONS: Low-dose denosumab every 3-6 months for
      about 2 years in two patients with JPD successfully controlled their bone
      disease. The long-term effect of denosumab on the nonskeletal complications
      remains to be elucidated.

PMID- 24433002
TI  - Extreme blood pressure oscillations in a patient with a MEN-2a syndrome.

PMID- 24433007
TI  - Targeted liposomal drug delivery systems for the treatment of B cell
      malignancies.
AB  - Nanoparticulate systems have demonstrated significant potential for overcoming
      the limitations of non-specific adverse effects related to chemotherapy. The
      treatment of blood malignancies employing targeted particulate drug delivery
      systems presents unique challenges and considerable research has been focused
      towards the development of targeted liposomal formulations for B cell
      malignancies. These formulations are aimed at achieving selectivity towards the
      malignant cells by targeting several cell surface markers which are over
      expressed in that specific malignancy. CD19, CD20, CD22 and CD74 are few of such
      markers of which CD19, CD22 and CD74 are internalizing and CD20 is non
      internalizing. Systems which have been developed to target both types of these
      cell surface markers are discussed. Specifically, the efficacy and development of
      targeted liposomes is considered. A number of studies have demonstrated the
      advantages of targeted liposomal systems encapsulating doxorubicin or
      vincristine. However, liposomal encapsulation of newer anti-neoplastic agents
      such as AD 198 which are superior to doxorubicin should be considered.

PMID- 24433008
TI  - Drug resistance to Mycobacterium tuberculosis: from the traditional Chinese view
      to modern systems biology.
AB  - The pathogen, Mycobacterium tuberculosis (M. tuberculosis) is a well-evolved,
      organized pathogen that has developed drug resistance, specifically multidrug
      resistance (MDR) and extensive drug resistance (XDR). This review primarily
      summarizes the mechanisms of drug resistance by M. tuberculosis according to the
      traditional Chinese view. The traditional Chinese view of drug resistance
      includes: the physical barrier of the cell wall; mutations relating to current
      anti-TB agents; drug efflux pumps; and drug stress, including the SOS response
      systems, the mismatch repair systems and the toxin-antitoxin systems. In
      addition, this review addresses the integrated systems biology of genomics,
      transcriptomics, proteomics, metabolomics and interactomics. Development of the
      various levels of systems biology has enabled determination of the anatomy of
      bacteria. Finally, the current review proposes that further investigation
      regarding the population of individuals with a high drug metabolic speed is vital
      to further understand drug resistance in M. tuberculosis. 

PMID- 24433009
TI  - Iridal-type triterpenoids with neuroprotective activities from Iris tectorum.
AB  - Six novel iridal-type triterpenoids with a previously unreported 3,6-dihydro-2H
      pyran moiety, named spirioiridotectals A-F (1-6), were isolated from the ethanol
      extract of the rhizomes of Iris tectorum. Their structures were elucidated on the
      basis of extensive spectroscopic analysis. Furthermore, in in vitro bioactivity
      assays, compounds 1, 2, and 6 exhibited neuroprotective activities against serum
      deprivation-induced PC12 cell damage. 

PMID- 24433013
TI  - Microwave-assisted fabrication of nanoparticulate TiO(2) microspheres for
      synergistic photocatalytic removal of Cr(VI) and methyl orange.
AB  - High yield production of micro/nanostructured nanoparticulate TiO2 microspheres
      (NTMs) via a facile microwave-assisted hydrothermal approach was investigated.
      The rapid and uniform microwave heating could reduce the reaction time to 30 min,
      an order of magnitude shorter than that of conventional hydrothermal methods. The
      characterization data confirmed that the resultant NTMs were highly uniform in
      size, having an average diameter of ~0.5 MUm. The obtained NTMs were found to be
      constructed by well-crystallized anatase phase nanoparticles ranging from 5 to 10
      nm that can be readily controlled by the microwave radiation temperature.
      Nitrogen sorption isotherm analysis revealed that the obtained NTMs possessed
      abundant mesoporous structures with a high specific surface area of 124 m(2) g(
      1). An in situ self-aggregation formation process under controllable pH in
      presence of urea was proposed. The results obtained from the application of NTMs
      for simultaneous photocatalytic decontamination of Cr(VI) and methyl orange (MO)
      demonstrated a strong synergistic effect that dramatically enhanced both Cr(VI)
      reduction and MO oxidation removal efficiencies. This work not only enriched the
      synthesis methods of the micro/nanostructured TiO2, but also provided a new means
      to improve the photocatalytic efficiency via structural-induced synergistic
      effect, applicable to the other catalysis systems. 

PMID- 24433014
TI  - Tracking single particles on supported lipid membranes: multimobility diffusion
      and nanoscopic confinement.
AB  - Supported lipid bilayers have been studied intensively over the past two decades.
      In this work, we study the diffusion of single gold nanoparticles (GNPs) with
      diameter of 20 nm attached to GM1 ganglioside or DOPE lipids at different
      concentrations in supported DOPC bilayers. The indefinite photostability of GNPs
      combined with the high sensitivity of interferometric scattering microscopy
      (iSCAT) allows us to achieve 1.9 nm spatial precision at 1 ms temporal
      resolution, while maintaining long recording times. Our trajectories visualize
      strong transient confinements within domains as small as 20 nm, and the
      statistical analysis of the data reveals multiple mobilities and deviations from
      normal diffusion. We present a detailed analysis of our findings and provide
      interpretations regarding the effect of the supporting substrate and GM1
      clustering. We also comment on the use of high-speed iSCAT for investigating
      diffusion of lipids, proteins, or viruses in lipid membranes with unprecedented
      spatial and temporal resolution. 

PMID- 24433015
TI  - Use of seat belt and enforcement of seat belt laws in Pakistan.
AB  - OBJECTIVES: Traffic crashes are a leading cause of deaths and injuries in
      Pakistan. The World Health Organization (WHO) estimates that approximately 30,131
      people die in road crashes annually on Pakistani roads (WHO 2013). The use of
      seat belts can be effective in reducing road crash fatalities in Pakistan but
      under existing seat belt laws, seat belt use is mandatory only for drivers and is
      limited to specific vehicles and roads. Primarily, this study was aimed to
      measure seat belt use rates among Pakistani vehicle occupants. It was meant to
      investigate the factors influencing the compliance behavior of seat belt use
      among vehicle drivers. The second objective was to gauge the enforcement of seat
      belt laws and their effectiveness in Pakistan. METHODS: A first ever national
      survey was conducted for the systematic recording of seat belt use rates among
      Pakistani drivers and front passengers on 5 different kinds of roads. Factors
      influencing compliance with seat belt use were gauged through a questionnaire for
      5 different kinds of roads. Commitment level of different traffic police
      organizations to enforce seat belt laws was also measured through their previous
      year's enforcement data. RESULTS: Average seat belt use rates were 20% with the
      highest on motorways (53%) and the lowest on rural roads (5%). Unawareness of the
      law/usefulness, seat belt not fitted, discomfort, forgetfulness, low speed, and
      careless attitude were major reasons for noncompliance with seat belt laws among
      Pakistani drivers. Seat belt use rates were directly proportional to law
      enforcement strength and the National Highways and Motorways Police (NH&MP)
      showed maximum enforcement on M-2. There is a dire need to revise existing seat
      belt laws in order to raise seat belt use rates in Pakistan.

PMID- 24433018
TI  - Effects of azelnidipine on uric acid metabolism in patients with essential
      hypertension.
AB  - PURPOSE: To examine effects of a long-acting calcium channel blocker (CCB)
      azelnidipine on uric acid metabolism in hypertensive patients. METHODS:
      Azelnidipine was administered to 72 patients at a daily dose of 8 mg or 16 mg. In
      22 cases out of the 72 patients, a different CCB was switched to azelnidipine.
      Blood pressure was measured and biochemical parameters of blood and urine were
      evaluated before and 2-3 months after the administration. RESULTS: Azelnidipine
      significantly decreased both systolic and diastolic blood pressure and the heart
      rate. It decreased both serum urate levels and the urinary uric acid to
      creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to
      creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and
      Cur/Ccr in patients with Uur/Ucr >= 0.5 or >= 0.34, although it did not change
      these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine
      decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric
      acid levels >= 7.0 mg/dL in males and >= 6.0 mg/dL in females. It did not change
      these parameters in normouricemic patients with serum urate levels <7.0 mg/dL in
      males and <6.0 mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in
      hyperuricemic patients with normal or over excretion of uric acid, although it
      did not change these clearance parameters in hyperuricemic patients with uric
      acid hypoexcretion. CONCLUSIONS: Azelnidipine decreased the serum urate acid
      levels and Uur/Ucr, and this response was most prominent in hyperuricemic
      patients or patients with normal and over excretion of uric acid.

PMID- 24433019
TI  - Combinatorial screening of inkjet printed ternary blends for organic
      photovoltaics: absorption behavior and morphology.
AB  - Inkjet printing was used for the preparation of ternary polymer/polymer/fullerene
      layers for organic solar cell application, as part of a combinatorial setup for
      the preparation and characterization of thin-film libraries. Poly(phenylene
      ethynylene)-alt-poly(phenylene-vinylene) (PPE-alt-PPV) and
      poly(diketopyrrolopyrrole-alt-fluorene) (P(DPP-alt-F)) were systematically
      blended with poly(3-octylthiophene) (P3OT) and investigated by UV-vis
      spectroscopy to improve the photon harvesting by extending the absorption range.
      The blends with the broadest absorption range (20 and 40 wt % of PPE-alt-PPV and
      P(DPP-alt-F), respectively) were mixed with mono(1-[3-(methoxycarbonyl)propyl]-1
      phenyl)-[6,6]C61 (PCBM). The blend with the low band gap polymer P(DPP-alt-F)
      revealed the most extended absorption, which ranges over the whole visible
      spectrum (350 to 750 nm). The mixing with PCBM (ratio 1/3) led to an optimal
      emission quenching and revealed a smooth film formation. In this contribution, we
      show that the combinatorial screening using inkjet printing represents an
      effective, time- and material-saving workflow for the investigation of polymer
      blend libraries, which is of high interest for the development of new materials
      for active layers in organic photovoltaics. 

PMID- 24433021
TI  - Sliding tarsal advancement flap for upper eyelid reconstruction.
AB  - The Sliding Tarsal Advancement Flap, a modification of Hughes procedure has been
      used for the repair of large upper eyelid defects in three patients. The
      procedure yielded both good functional and aesthetic outcomes. At presentation
      the defect measured 50% in two cases and >50% in one case.

PMID- 24433022
TI  - In situ spatially and temporally resolved measurements of salt concentration
      between charging porous electrodes for desalination by capacitive deionization.
AB  - Capacitive deionization (CDI) is an emerging water desalination technique. In
      CDI, pairs of porous electrode capacitors are electrically charged to remove salt
      from brackish water present between the electrodes. We here present a novel
      experimental technique allowing measurement of spatially and temporally resolved
      salt concentration between the CDI electrodes. Our technique measures the local
      fluorescence intensity of a neutrally charged fluorescent probe which is
      collisionally quenched by chloride ions. To our knowledge, our system is the
      first to measure in situ and spatially resolved chloride concentration in a
      laboratory CDI cell. We here demonstrate good agreement between our dynamic
      measurements of salt concentration in a charging, millimeter-scale CDI system to
      the results of a modified Donnan porous electrode transport model. Further, we
      utilize our dynamic measurements to demonstrate that salt removal between our
      charging CDI electrodes occurs on a longer time scale than the capacitive
      charging time scales of our CDI cell. Compared to typical measurements of CDI
      system performance (namely, measurements of outflow ionic conductivity), our
      technique can enable more advanced and better-controlled studies of ion transport
      in CDI systems, which can potentially catalyze future performance improvements. 

PMID- 24433025
TI  - Treatment with thyroid hormone.
AB  - Thyroid hormone deficiency can have important repercussions. Treatment with
      thyroid hormone in replacement doses is essential in patients with
      hypothyroidism. In this review, we critically discuss the thyroid hormone
      formulations that are available and approaches to correct replacement therapy
      with thyroid hormone in primary and central hypothyroidism in different periods
      of life such as pregnancy, birth, infancy, childhood, and adolescence as well as
      in adult patients, the elderly, and in patients with comorbidities. Despite the
      frequent and long term use of l-T4, several studies have documented frequent
      under- and overtreatment during replacement therapy in hypothyroid patients. We
      assess the factors determining l-T4 requirements (sex, age, gender, menstrual
      status, body weight, and lean body mass), the major causes of failure to achieve
      optimal serum TSH levels in undertreated patients (poor patient compliance,
      timing of l-T4 administration, interferences with absorption, gastrointestinal
      diseases, and drugs), and the adverse consequences of unintentional TSH
      suppression in overtreated patients. Opinions differ regarding the treatment of
      mild thyroid hormone deficiency, and we examine the recent evidence favoring
      treatment of this condition. New data suggesting that combined therapy with T3
      and T4 could be indicated in some patients with hypothyroidism are assessed, and
      the indications for TSH suppression with l-T4 in patients with euthyroid
      multinodular goiter and in those with differentiated thyroid cancer are reviewed.
      Lastly, we address the potential use of thyroid hormones or their analogs in
      obese patients and in severe cardiac diseases, dyslipidemia, and nonthyroidal
      illnesses. 

PMID- 24433026
TI  - Characterization of KPC-2-producing Escherichia coli, Citrobacter freundii,
      Enterobacter cloacae, Enterobacter aerogenes, and Klebsiella oxytoca isolates
      from a Chinese Hospital.
AB  - Twelve nonduplicated KPC-2-producing enterobacterial isolates, including three
      Escherichia coli, two Citrobacter freundii, two Enterobacter cloacae, four
      Enterobacter aerogenes, and one Klebsiella oxytoca, were collected from various
      clinical samples within 18 months (March 2011 to September 2012). Two of the 12
      patients died from infections caused by KPC-2-producing pathogens, while the rest
      of the patients with KPC-2-producing pathogens improved or were cured. The
      majority of the clinical isolates exhibited a high-level of resistance to
      oxyimino-cephalosporins and carbapenems, and possessed self-transferable bla(KPC
      2)-carrying plasmids with sizes ranging from 20 to 120 kb. Most isolates carried
      bla(CTX-M) and plasmid-mediated quinolone resistance genes, while some isolates
      produced 16S rRNA methylases (ArmA or RmtB). The genetic environment of bla(KPC
      2) of most clinical strains was consistent with the genetic structure surrounding
      bla(KPC-2) on the plasmid pKP048, which contains an integration structure of a
      Tn3-based transposon and partial Tn4401 segment. Inserted fragments (truncated
      bla(TEM)) were detected upstream of the bla(KPC-2) gene for two E. aerogenes
      strains. In conclusion, the enterobacterial isolates exhibited sporadic emergence
      and did not arise by clonal spread at our hospital. The outcome of infections
      caused by KPC-producing enterobacterial isolates and their mortality were closely
      associated with the baseline condition of patients. The spread of bla(KPC-2) gene
      between different enterobacterial species in China was mainly mediated by
      horizontal transfer of the Tn3-based transposons and not the bla(KPC-2)-carrying
      plasmids.

PMID- 24433029
TI  - Role of electronic-vibrational mixing in enhancing vibrational coherences in the
      ground electronic states of photosynthetic bacterial reaction center.
AB  - We describe polarization controlled two-color coherence photon echo studies of
      the reaction center complex from a purple bacterium Rhodobacter sphaeroides. Long
      lived oscillatory signals that persist up to 2 ps are observed in neutral,
      oxidized, and mutant (lacking the special pair) reaction centers, for both (0
      degrees ,0 degrees ,0 degrees ,0 degrees ) and (45 degrees ,-45 degrees ,90
      degrees ,0 degrees ) polarization sequences. We show that the long-lived signals
      arise via vibronic coupling of the bacteriopheophytin (H) and accessory
      bacteriochlorophyll (B) pigments that leads to vibrational wavepackets in the B
      ground electronic state. Fourier analysis of the data suggests that the 685 cm(
      1) mode of B may play a key role in the H to B energy transfer. 

PMID- 24433027
TI  - Treatment of experimental autoimmune encephalomyelitis by codelivery of disease
      associated Peptide and dexamethasone in acetalated dextran microparticles.
AB  - Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central
      nervous system that can cause loss of motor function and is thought to result, in
      part, from chronic inflammation due to an antigen-specific T cell immune
      response. Current treatments suppress the immune system without antigen
      specificity, increasing the risks of cancer, chronic infection, and other long
      term side effects. In this study, we show treatment of experimental autoimmune
      encephalomyelitis (EAE), a model of MS, by coencapsulating the immunodominant
      peptide of myelin oligodendrocyte glycoprotein (MOG) with dexamethasone (DXM)
      into acetalated dextran (Ac-DEX) microparticles (DXM/MOG/MPs) and administering
      the microparticles subcutaneously. The clinical score of the mice was reduced
      from 3.4 to 1.6 after 3 injections 3 days apart with the coencapsulated
      microparticulate formulation (MOG 17.6 MUg and DXM 8 MUg). This change in
      clinical score was significantly greater than observed with phosphate-buffered
      saline (PBS), empty MPs, free DXM and MOG, DXM/MPs, and MOG/MPs. Additionally,
      treatment with DXM/MOG/MPs significantly inhibited disease-associated cytokine
      (e.g., IL-17, GM-CSF) expression in splenocytes isolated in treated mice. Here we
      show a promising approach for the therapeutic treatment of MS using a polymer
      based microparticle delivery platform. 

PMID- 24433030
TI  - Spinal fracture-dislocations and spinal cord injuries in motor vehicle crashes.
AB  - PURPOSE: This study estimated the annual count of spinal cord injuries (SCIs) in
      motor vehicles crashes by type and seat belt use using 18 years of NASS-CDS data.
      It determined the rate for SCI and fracture-dislocation of the spine. METHODS:
      1994-2011 NASS-CDS was used to estimate the annual occurrence of spinal injuries
      in front seat occupants involved in motor vehicle crashes. Crashes were grouped
      by front, side, rear, and rollovers, and the effects of belt use were
      investigated. Light vehicles were included with model year 1994+. Spinal injuries
      were classified as minor (Abbreviated Injury Scale [AIS] 1), moderate (AIS 2),
      serious (AIS 3), fracture-dislocations, and SCI (AIS 4+). The annual count and
      rate for different types of spinal injury were estimated along with standard
      errors. The results were compared to estimates of head injuries. NASS-CDS
      electronic cases of SCIs in rear impacts were investigated. RESULTS: There were
      5,592 +/- 1,170 fracture-dislocations of the spine and 1,046 +/- 193 AIS 4+ SCI
      per year in motor vehicle crashes. Most of the injuries occurred in rollovers and
      frontal crashes and the least occurred in rear impacts. The rate of SCI was 0.054
      +/- 0.010%. The highest rate was 0.220 +/- 0.056% in rollover crashes and the
      lowest rate was 0.032 +/- 0.009% in frontal crashes. The highest rate for spinal
      fracture-dislocation was 1.552 +/- 0.455% in rollovers and the lowest was 0.065
      +/- 0.021% in rear impacts. The rate for SCI was 0.027 +/- 0.005% in belted and
      0.145 +/- 0.028% in unbelted occupants giving 81% effectiveness of belt use in
      reducing SCI. The cervical spine was associated with 66.3 +/- 11.3% of the AIS 4+
      SCI with 30.5 +/- 7.4% in the thoracic spine and 3.2 +/- 1.3% in the lumbar
      spine. Severe head injuries occurred 13.3 times more often than SCIs.
      CONCLUSIONS: Spinal cord injury occurred in one out of 1,860 front seat occupants
      in tow-away crashes. The rate was highest in rollover crashes and was reduced by
      seat belt use. Fracture-dislocation of the spine occurred about 5.3 times more
      often than SCIs and was also prevented by seat belt use.

PMID- 24433031
TI  - Validity of salt intake assessment system based on a 24-h dietary recall method
      using a touch panel computer.
AB  - BACKGROUND: An electronic system for salt intake assessment using a 24-h dietary
      recall method has been developed in Japan. We evaluated the validity of this salt
      intake system for assessing salt intake. METHODS: We prospectively obtained data
      on estimated salt intake using 24-hour urinary sodium excretion (24-hUNaCl) and
      salt intake by the salt intake assessment system from 203 consecutive outpatients
      with essential hypertension (age: 67.8 +/- 10.7 years; 53.7% men). RESULTS: Mean
      values were 9.7 +/- 2.9 g/day for 24-hUNaCl and 9.1 +/- 2.9 g/day for the salt
      intake assessment system before corrections. The salt intake estimated by the
      present system was significantly correlated with 24-hUNaCl (r = 0.66, p <
      0.0001). After corrections for habitual use of discretionary seasonings, habitual
      intake of salty foods, and physical activity, correlation coefficients between
      salt intake and 24-hUNaCl increased from 0.60 to 0.66 in men <65 years, from 0.80
      to 0.81 in men >= 65 years, from 0.64 to 0.75 in women <65 years, and from 0.52
      to 0.59 in women >= 65 years. After further correction for regional differences
      in average salt intake, the correlation coefficient reached 0.72 in all patients.
      CONCLUSION: After correction for dietary habits, lifestyle factors, and
      differences in average salt intake by region, this system may be a useful tool in
      Japan to encourage salt restriction in the clinical treatment of hypertension and
      improve public health in terms of salt restriction overall.

PMID- 24433032
TI  - Highly efficient polymer-based optoelectronic devices using PEDOT:PSS and a GO
      composite layer as a hole transport layer.
AB  - We demonstrate highly efficient polymer light-emitting diodes (PLEDs), as well as
      polymer solar cells (PSCs), using a solution-processable poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS):graphene oxide (GO)
      (PEDOT:GO) composite layer as hole transport layers (HTLs). The PEDOT:GO
      composite HTL layer shows enhanced charge carrier transport due to improved
      conductivity by benzoid-quinoid transitions with a well-matched work function
      between GO (4.89 eV) and PEDOT:PSS (4.95 eV). Moreover, it reduces remarkably
      exciton quenching and suppresses recombinations that bring higher charge
      extraction in PSCs and increases the recombinations of holes and electrons within
      the active layer by the blocking behavior of the electrons from a fluorescent
      semiconductor due to the existence of GO with large bandgap (~3.6 eV) in the
      PEDOT:GO composite layer, therefore leading to an enhancement of device
      efficiency in PLEDs and PSCs. The optimized PLEDs and PSCs with a PEDOT:GO
      composite HTL layer shows the maximum luminous efficiency of 21.74 cd/A (at 6.4
      V) for PLEDs, as well as the power conversion efficiency of 8.21% for PSCs, which
      were improved by ~220 and 12%, respectively, compared to reference PLEDs and PSCs
      with a PEDOT:PSS layer. 

PMID- 24433033
TI  - Comparision of osteoconductivity of biologic and artificial synthetic
      hydroxyapatite in experimental mastoid obliteration.
AB  - CONCLUSIONS: To our knowledge, this is the first in vivo study to address the
      comparison between biologic hydroxyapatite (BHA) and artificial HA (AHA)
      materials for mastoid obliteration. From our results, it is believed that BHA has
      better osteoconductivity than AHA. OBJECTIVE: The purpose of this study was to
      compare the osteoconductivity of AHA and BHA in a mastoid obliteration model in
      rats. METHODS: BHA and AHA were fabricated. Bulla obliteration was carried out in
      group A (n = 10, BHA) and group B (n = 10, AHA). The animals were administered
      fluorescent bone labels for a qualitative evaluation of bone formation.
      Oxytetracycline hydrochloride was administered at 2 weeks, calcein at 4 weeks,
      and alizarin red at 8 weeks. The animals were sacrificed at 12 weeks post
      surgery. They were evaluated by micro-CT and histological investigation. RESULTS:
      Neither BHA nor AHA exhibited signs of resorption until 12 weeks of obliteration.
      However, the accelerated osteoconductive bone formation in the BHA group was
      better than in the AHA group according to micro-CT and confocal microscopic
      findings.

PMID- 24433037
TI  - Endogenous IFNlambda in viral hepatitis patients.
AB  - Besides type I interferons (IFNs), type III IFNs, including IFNlambda1
      (interleukin-29 [IL-29]), possess potent antiviral activity. In patients infected
      with the hepatitis C virus (HCV), it has been demonstrated that viral clearance
      is associated with genetic variation near the IFNlambda3 (IL-28B) gene. The rapid
      influx of research being conducted on this family of cytokines has led to several
      inconsistencies and controversies, including the possible correlation of serum
      cytokine levels with disease in chronic viral hepatitis patients. In a detailed
      study, well-characterized cohorts of patients with HBV and HCV were evaluated
      with 3 different immunoassays, and no differences in the levels of serum
      IFNlambda were observed between patient groups, disease stages, or clinical
      parameters. 

PMID- 24433038
TI  - Report of a phase I evaluation of dose and schedule of interleukin-1 alpha and
      cyclophosphamide in patients with advanced tumors: An Eastern Cooperative
      Oncology Group study (PX990) and review of IL-1-based studies of hematopoietic
      reconstitution.
AB  - Interleukin-1 (IL-1) is a cytokine critical to inflammation, immunological
      activation, response to infection, and bone marrow hematopoiesis.
      Cyclophosphamide downmodulates immune suppressor cells and is cytotoxic to a
      variety of tumors. A phase I trial of IL-1 and cyclophosphamide was conducted by
      the Eastern Cooperative Oncology Group. This study evaluated 3 dose levels and 3
      schedules in patients with solid tumors. The goal was to evaluate the
      hematopoietic supportive care effect and possible antitumor effect. Toxicity was
      fever, chills, hypotension, nausea/emesis, hepatic, and neutropenia. Toxicity
      increased with dose increases of interleukin-1. Treatment at all dose levels
      resulted in significant increases in total white blood cell (WBC) counts above
      baseline. Nadir WBC and nadir absolute neutrophil counts were not significantly
      different by dose level of IL-1 or schedule of IL-1. Toxicity due to IL-1 at
      higher doses prohibited further evaluation of this agent for hematopoietic
      support, particularly in view of the activity and tolerability of more lineage
      specific hematopoietic cytokines. Therapeutic interventions in the role of IL-1
      in inflammatory conditions and cancer may be further informed by our definition
      of its clinical and biological effects in this evaluation of dose and schedule.

PMID- 24433040
TI  - Prolactin/Stat5 and androgen R1881 coactivate carboxypeptidase-D gene in breast
      cancer cells.
AB  - Plasma membrane-bound carboxypeptidase-D (CPD) cleaves C-terminal arginine from
      extracellular substrates. In the cell, arginine is converted to nitric oxide
      (NO). We have reported that up-regulation of CPD mRNA/protein levels by 17beta
      estradiol and prolactin (PRL) in breast cancer cells, and by testosterone in
      prostate cancer cells, increased NO production and cell survival. The CPD
      promoter contains a consensus gamma-interferon-activated sequence (GAS) and 3
      putative androgen response elements (ARE.1, ARE.2, ARE.3) that could potentially
      bind PRL-activated transcription factor Stat5 (signal transducer and activator of
      transcription 5) and the liganded androgen receptor (AR), respectively. This
      study showed that synthetic androgen R1881 and PRL elevated CPD mRNA/protein
      levels in human MCF-7 and T47D breast cancer cells in a time-/dose-dependent
      manner. PRL/R1881-elevated CPD expression was blocked by actinomycin-D, and a CPD
      promoter construct containing these GAS and AREs was stimulated by PRL or R1881,
      indicating transcriptional regulation by both hormones. Luciferase reporter
      assays showed that GAS and the adjacent ARE.1 only were active. Mutation of GAS
      in the DeltaGAS-CPD construct (ARE.1 intact) abolished CPD promoter activity in
      response to PRL and, surprisingly, to R1881 as well. DeltaGAS-CPD promoter
      activity was restored by PRL+R1881 in combination, and enhanced by ectopic Stat5,
      but abolished by Stat5 gene knockdown. Chromatin immunoprecipitation analysis
      confirmed binding of activated Stat5 and liganded AR to GAS and ARE.1,
      respectively. Activated Stat5 also induced binding of unliganded AR to ARE.1, and
      liganded AR induced binding of unactivated Stat5 to GAS. In summary, PRL and
      R1881, acting through Stat5 and AR, act cooperatively to stimulate CPD gene
      transcription in breast cancer cells. 

PMID- 24433044
TI  - Energy level realignment in weakly interacting donor-acceptor binary molecular
      networks.
AB  - Understanding the effect of intermolecular and molecule-substrate interactions on
      molecular electronic states is key to revealing the energy level alignment
      mechanism at organic-organic heterojunctions or organic-inorganic interfaces. In
      this paper, we investigate the energy level alignment mechanism in weakly
      interacting donor-acceptor binary molecular superstructures, comprising copper
      hexadecafluorophthalocyanine (F16CuPc) intermixed with copper phthalocyanine
      (CuPc), or manganese phthalocynine (MnPc) on graphite. The molecular electronic
      structures have been systematically studied by in situ ultraviolet photoelectron
      spectroscopy (UPS) and low-temperature scanning tunneling microscopy/spectroscopy
      (LT-STM/STS) experiments and corroborated by density functional theory (DFT)
      calculations. As demonstrated by the UPS and LT-STM/STS measurements, the
      observed unusual energy level realignment (i.e., a large downward shift in donor
      HOMO level and a corresponding small upward shift in acceptor HOMO level) in the
      CuPc-F16CuPc binary superstructures originates from the balance between
      intermolecular and molecule-substrate interactions. The enhanced intermolecular
      interactions through the hydrogen bonding between neighboring CuPc and F16CuPc
      can stabilize the binary superstructures and modify the local molecular
      electronic states. The obvious molecular energy level shift was explained by gap
      state-mediated interfacial charge transfer. 

PMID- 24433042
TI  - Nanofiber scaffolds with gradients in mineral content for spatial control of
      osteogenesis.
AB  - Reattachment of tendon to bone has been a challenge in orthopedic surgery. The
      disparate mechanical properties of the two tissues make it difficult to achieve
      direct surgical repair of the tendon-to-bone insertion. Healing after surgical
      repair typically does not regenerate the natural attachment, a complex tissue
      that connects tendon and bone across a gradient in both mineral content and cell
      phenotypes. To facilitate the regeneration of the attachment, our groups have
      developed a nanofiber-based scaffold with a graded mineral coating to mimic the
      mineral composition of the native tendon-to-bone insertion. In the present work,
      we evaluated the ability of this scaffold to induce graded osteogenesis of
      adipose-derived mesenchymal stem cells (ASCs). Results from 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferating
      cell nuclear antigen staining indicated that cell proliferation was negatively
      correlated with the mineral content. In contrast, alkaline phosphatase staining,
      an indicator of osteogenesis, was positively correlated with the mineral content.
      Likewise, runt-related transcription factor 2 (an early marker of osteoblast
      differentiation) and osteocalcin (a late marker of osteoblast differentiation)
      immunostaining were both positively correlated with the mineral content. These
      results indicate that a gradient in mineral content on the surface of a nanofiber
      scaffold is capable of inducing graded differentiation of ASCs into osteoblasts
      for enthesis repair. 

PMID- 24433043
TI  - The prevalence, predictors and associations of hypertension in Sri Lanka: a cross
      sectional population based national survey.
AB  - We studied the community prevalence, patterns and predictors of hypertension in a
      large sub-population of South Asian adults with a view of identifying
      differential risk factors. Data were collected between years 2005-2006 and 5000
      adults were invited for the study. The sample size was 4485, and about 39.5% were
      males. Mean systolic and diastolic blood pressures were 127.1 +/- 19.8 mmHg and
      75.4 +/- 11.3 mmHg, respectively. Age-adjusted prevalence in all adults, males
      and females was 23.7%, 23.4% and 23.8%, respectively. Urban adults had a
      significantly higher prevalence of hypertension than rural adults. In the binary
      logistic-regression analysis, male gender (OR: 1.2), increasing age, Sri Lankan
      Moor ethnicity (OR: 1.6), physical inactivity (OR: 1.7), presence of diabetes
      (OR: 2.2) and central obesity (OR: 2.3) all were significantly associated with
      hypertension. In conclusion, nearly one-third of the Sri Lankan adult population
      is hypertensive. Hence, public health initiatives should encourage healthier
      lifestyles with emphasis on preventing obesity and increasing physical activity.

PMID- 24433041
TI  - Minireview: More than just a hammer: ligand "bias" and pharmaceutical discovery.
AB  - Conventional orthosteric drug development programs targeting G protein-coupled
      receptors (GPCRs) have focused on the concepts of agonism and antagonism, in
      which receptor structure determines the nature of the downstream signal and
      ligand efficacy determines its intensity. Over the past decade, the emerging
      paradigms of "pluridimensional efficacy" and "functional selectivity" have
      revealed that GPCR signaling is not monolithic, and that ligand structure can
      "bias" signal output by stabilizing active receptor states in different
      proportions than the native ligand. Biased ligands are novel pharmacologic
      entities that possess the unique ability to qualitatively change GPCR signaling,
      in effect creating "new receptors" with distinct efficacy profiles driven by
      ligand structure. The promise of biased agonism lies in this ability to engender
      "mixed" effects not attainable using conventional agonists or antagonists,
      promoting therapeutically beneficial signals while antagonizing deleterious ones.
      Indeed, arrestin pathway-selective agonists for the type 1 parathyroid hormone
      and angiotensin AT1 receptors, and G protein pathway-selective agonists for the
      GPR109A nicotinic acid and MU-opioid receptors, have demonstrated unique, and
      potentially therapeutic, efficacy in cell-based assays and preclinical animal
      models. Conversely, activating GPCRs in "unnatural" ways may lead to downstream
      biological consequences that cannot be predicted from prior knowledge of the
      actions of the native ligand, especially in the case of ligands that selectively
      activate as-yet poorly characterized G protein-independent signaling networks
      mediated via arrestins. Although much needs to be done to realize the clinical
      potential of functional selectivity, biased GPCR ligands nonetheless appear to be
      important new additions to the pharmacologic toolbox. 

PMID- 24433046
TI  - Bubble liposomes and ultrasound exposure improve localized morpholino oligomer
      delivery into the skeletal muscles of dystrophic mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a genetic disorder that is caused by
      mutations in the DMD gene that lead to an absence of functional protein. The mdx
      dystrophic mouse contains a nonsense mutation in exon 23 of the dystrophin gene;
      a phosphorodiamidate morpholino oligomer (PMO) designed to skip this mutated exon
      in the mRNA induces dystrophin expression. However, an efficient PMO delivery
      method is needed to improve treatment strategies for DMD. We previously developed
      polyethylene glycol (PEG)-modified liposomes (Bubble liposomes) that entrap
      ultrasound contrast gas and demonstrated that the combination of Bubble liposomes
      with ultrasound exposure is an effective gene delivery tool in vitro and in vivo.
      In this study, to evaluate the ability of Bubble liposomes as a PMO delivery
      tool, we tested the potency of the Bubble liposomes combined with ultrasound
      exposure to boost the delivery of PMO and increase the skipping of the mutated
      exon in the mdx mouse. The results indicated that the combination of Bubble
      liposomes and ultrasound exposure increased the uptake of the PMO targeting a
      nonsense mutation in exon 23 of the dystrophin gene and consequently increased
      the PMO-mediated exon-skipping efficiency compared with PMO injection alone,
      leading to significantly enhanced dystrophin expression. This increased
      efficiency indicated the potential of the combination of Bubble liposomes with
      ultrasound exposure to enhance PMO delivery for treating DMD. Thus, this
      ultrasound-mediated Bubble liposome technique may provide an effective,
      noninvasive, nonviral method for PMO therapy for DMD muscle as well as for other
      muscular dystrophies. 

PMID- 24433047
TI  - Retraction. Dimerization of an immunoactivating peptide derived from
      mycobacterial hsp65 using N-hydroxysuccinimide based bifunctional reagents is
      critical for its antitumor properties.

PMID- 24433048
TI  - Synthetic access to a hydrocarbon-soluble trifluorinated Ge(II) compound and its
      Sn(II) congener.
AB  - Trifluorinated germanium anions attracted attention of theoretical chemists
      already in the late 1990s to predict their physical and chemical properties.
      However these species were not synthesized in the laboratory, although
      substantial evidence for their existence was obtained from the mass spectrometry
      of GeF4. The present study shows that controlled fluorination of LMNMe2 (L =
      PhC(N(t)Bu)2, M = Ge, Sn) using HF.pyridine in toluene leads to the formation of
      [LH2](+)[MF3](-) under elimination of HNMe2. The products contain the
      trifluorinated Ge(II) and Sn(II) anionic species which are stabilized by
      interionic H...F bonds. The new compounds were characterized by single crystal X
      ray structural analysis, NMR spectroscopy, and elemental analysis. 

PMID- 24433050
TI  - Evaluation of NASS-CDS side crash delta-V estimates using event data recorders.
AB  - OBJECTIVE: Planar crash severity is most commonly defined by delta-V (DeltaV),
      which is the change in a vehicle's velocity vector during a crash. All DeltaV
      estimates contained in the NASS-CDS are generated using a damage-based program
      called WinSMASH. WinSMASH DeltaV accuracy in side crashes has not previously been
      validated against real-world crash data. This study will investigate the accuracy
      of WinSMASH DeltaV estimates in real-world side crashes. METHODS: This study uses
      biaxial DeltaV data from event data recorders (EDRs) to assess the accuracy of
      side crash DeltaV estimates in NASS-CDS crash cases. Single-event side crashes
      were identified in the NASS-CDS for which (a) WinSMASH DeltaV had been coded and
      (b) biaxial EDR data were available. For these crashes, the WinSMASH-estimated
      resultant DeltaV was compared with the EDR-recorded resultant DeltaV to assess
      the accuracy of the former. EDR DeltaV values were adjusted for an assumed
      average restitution value of 10 percent, based on values reported in the
      literature. Principal direction of force (PDOF) is the orientation of the net
      crash impulse relative to the vehicle and is a key parameter in WinSMASH
      reconstructions. NASS-CDS PDOF estimates were compared to the PDOF computed from
      the EDR data to assess their accuracy as well. RESULTS: WinSMASH systematically
      overestimates EDR DeltaV by about 12.9 percent for cars struck by cars and by
      about 2.4 percent for cars struck by light trucks and vans (LTVs). DeltaV error
      was significantly different (at 95% confidence) for crashes to different areas of
      the vehicle side. The mean discrepancy in NASS-CDS PDOF was -0.9 degrees  with a
      standard deviation of 12.6 degrees . DISCUSSION: WinSMASH systematically
      overestimates DeltaV at common velocity by about 13 percent for cars struck by
      cars and about 2 percent for cars struck by LTVs. Since WinSMASH's assumption of
      zero restitution is accounted for in this analysis, this suggests that WinSMASH
      stiffness parameters represent LTV impacts better than car impacts in side
      crashes. DeltaV error differs by impacted area, suggesting that side impact
      stiffness parameters used in damage-based DeltaV reconstruction must closely
      represent the crash mode being reconstructed for best results. NASS-CDS estimates
      of PDOF do not appear to exhibit any systematic discrepancy. The amount of random
      PDOF discrepancy observed here is consistent with prior studies.

PMID- 24433049
TI  - The most effective gold nanorod size for plasmonic photothermal therapy: theory
      and in vitro experiments.
AB  - The development of new and improved photothermal contrast agents for the
      successful treatment of cancer (or other diseases) via plasmonic photothermal
      therapy (PPTT) is a crucial part of the application of nanotechnology in
      medicine. Gold nanorods (AuNRs) have been found to be the most effective
      photothermal contrast agents, both in vitro and in vivo. Therefore, determining
      the optimum AuNR size needed for applications in PPTT is of great interest. In
      the present work, we utilized theoretical calculations as well as experimental
      techniques in vitro to determine this optimum AuNR size by comparing plasmonic
      properties and the efficacy as photothermal contrast agents of three different
      sizes of AuNRs. Our theoretical calculations showed that the contribution of
      absorbance to the total extinction, the electric field, and the distance at which
      this field extends away from the nanoparticle surface all govern the
      effectiveness of the amount of heat these particles generate upon NIR laser
      irradiation. Comparing between three different AuNRs (38 * 11, 28 * 8, and 17 * 5
      nm), we determined that the 28 * 8 nm AuNR is the most effective in plasmonic
      photothermal heat generation. These results encouraged us to carry out in vitro
      experiments to compare the PPTT efficacy of the different sized AuNRs. The 28 * 8
      nm AuNR was found to be the most effective photothermal contrast agent for PPTT
      of human oral squamous cell carcinoma. This size AuNR has the best compromise
      between the total amount of light absorbed and the fraction of which is converted
      to heat. In addition, the distance at which the electric field extends from the
      particle surface is most ideal for this size AuNR, as it is sufficient to allow
      for coupling between the fields of adjacent particles in solution (i.e., particle
      aggregates), resulting in effective heating in solution. 

PMID- 24433051
TI  - Global mercury emissions from combustion in light of international fuel trading.
AB  - The spatially resolved emission inventory is essential for understanding the fate
      of mercury. Previous global mercury emission inventories for fuel combustion
      sources overlooked the influence of fuel trading on local emission estimates of
      many countries, mostly developing countries, for which national emission data are
      not available. This study demonstrates that in many countries, the mercury
      content of coal and petroleum locally consumed differ significantly from those
      locally produced. If the mercury content in locally produced fuels were used to
      estimate emission, then the resulting global mercury emissions from coal and
      petroleum would be overestimated by 4.7 and 72%, respectively. Even higher
      misestimations would exist in individual countries, leading to strong spatial
      bias. On the basis of the available data on fuel trading and an updated global
      fuel consumption database, a new mercury emission inventory for 64 combustion
      sources has been developed. The emissions were mapped at 0.1 degrees  * 0.1
      degrees  resolution for 2007 and at country resolution for a period from 1960 to
      2006. The estimated global total mercury emission from all combustion sources
      (fossil fuel, biomass fuel, solid waste, and wildfires) in 2007 was 1454 Mg (1232
      1691 Mg as interquartile range from Monte Carlo simulation), among which
      elementary mercury (Hg(0)), divalent gaseous mercury (Hg(2+)), and particulate
      mercury (Hg(p)) were 725, 548, and 181 Mg, respectively. The total emission from
      anthropogenic sources, excluding wildfires, was 1040 Mg (886-1248 Mg), with coal
      combustion contributing more than half. Globally, total annual anthropogenic
      mercury emission from combustion sources increased from 285 Mg (263-358 Mg) in
      1960 to 1040 Mg (886-1248 Mg) in 2007, owing to an increased fuel consumption in
      developing countries. However, mercury emissions from developed countries have
      decreased since 2000. 

PMID- 24433055
TI  - Delayed facial nerve palsy after surgery for the Esteem((r)) fully implantable
      middle ear hearing device.
AB  - CONCLUSION: Delayed facial nerve (FN) impairment was shown to occur after
      Esteem((r)) surgery, and taste disturbances were found in a limited number of
      subjects. Thus, when this type of active middle ear implant (AMEI) is to be
      implanted, these specific complications need to be shared with the candidate.
      OBJECTIVES: To report on FN involvement in Esteem((r)) AMEI surgery. METHODS: A
      total of 23 males and 11 females, who presented with sensorineural hearing loss
      of varying severity, underwent surgical implantation of the Esteem((r)) AMEI. FN
      function was assessed according to the House-Brackmann (HB) grading system. A
      specific question regarding taste impairment was administered to each patient on
      the first day and 3 months after surgery. RESULTS: None of the patients presented
      with a FN deficit in the first postoperative days. In three patients (8.8%), FN
      palsy developed after 7 days (two patients) and 10 days (one patient), and the
      severities were HB 4 (two cases) and HB 5 (one case). All patients fully
      recovered (HB 1) after 6-8 weeks. In 10 of the 34 implanted subjects (29.4%),
      taste disturbances were found on postoperative day 1, and these impairments
      remained in only 6 (17.6%) patients at the 3-month postoperative follow-up.

PMID- 24433056
TI  - Therapeutic effectiveness of endoscopic vidian neurectomy for the treatment of
      vasomotor rhinitis.
AB  - CONCLUSION: Our results indicate that vidian neurectomy may be recommended as an
      effective method for the treatment of vasomotor rhinitis (VMR). OBJECTIVE: The
      aim of this work was to study the feasibility and effectiveness of vidian
      neurectomy treatment under the nasal endoscope for VMR. METHODS: The study
      included 45 patients with VMR. They were all assigned to functional endoscopic
      surgery with vidian neurectomy. RESULTS: The obtained data showed that, using the
      rhinoconjunctivitis quality of life questionnaire, vidian neurectomy treatment
      relieved the symptoms of VMR in 82.2% of the patients. Vidian neurectomy also led
      to the reduction of expression of several cytokines, including vasoactive
      intestinal polypeptide, calcitonin gene-related peptide, substance P, interleukin
      (IL)-4, and IL-5.

PMID- 24433057
TI  - Voice and quality of life in patients with recurrent respiratory papillomatosis
      in a northern Sweden cohort.
AB  - CONCLUSION: The frequency of operations, age at onset, gender and subtype of the
      human papilloma virus (HPV) may be used as factors to predict voice disability.
      OBJECTIVES: Patients with recurrent respiratory papillomatosis (RRP) are
      characterized by morbid consequences due to a lifelong repetitive influence on
      voice and breathing ability and the need for recurrent surgical treatments. The
      aim of the study was to measure the quality of voice and life using evaluated and
      validated questionnaires in a northern Sweden RRP population. METHODS: A total of
      27 consecutive patients with RRP (age 21-71 years, median 47 years) were
      evaluated 3 months postoperatively (CO2 laser treatment) using the voice handicap
      index (VHI) and SF-36 questionnaires to assess the impact on life and voice in an
      RRP population. The values were compared to historical normative data, VHI <= 20.
      RESULTS: Patients that underwent more than one operation per year were younger (p
      = 0.028) than those treated less frequently. The mean VHItotal score in patients
      with RRP was 39.3, indicating a statistically significant impairment of voice
      quality (p < 0.001) as compared with normal subjects. Voice dysfunction was
      observed in 21 patients (78%). Significantly lower values than the normal
      population regarding the quality of life in patients with RRP were obtained in
      the domain of social functioning (p = 0.029). Females, patients with frequent
      surgical treatment sessions and patients with the high-risk HPV types scored
      significantly lower in several domains of the quality of life assessment as
      compared with normal subjects. The results should be interpreted with caution due
      to the limited number of subjects.

PMID- 24433059
TI  - Direct intense pulsed light sintering of inkjet-printed copper oxide layers
      within six milliseconds.
AB  - We demonstrate intense pulsed light (IPL) sintering of inkjet-printed CuO layers
      on a primer-coated porous PET substrate to convert the electrically insulating
      CuO into conductive Cu. With this approach, conductive layers are obtained in
      less than 1 s after the printing process. The IPL sintering was performed for
      high productivity with minimum duration and repetition of IPL irradiation to
      evaluate the effect of pulse number and energy output on the conductivity and
      morphology of the sintered Cu layers. Depending on the energy output, sheet
      resistances were measured as 0.355, 0.131, and 0.121 Omega.?(-1) by exposure
      energy of 5.48 (single pulse), 7.03 (double pulse), and 7.48 J.cm(-2) (triple
      pulse), respectively. In contrast, an excessive energy with relatively short
      pulse duration causes a delamination of the Cu layer. The lowest resistivity of
      about 55.4 nOmega.m (corresponds to about 30% conductivity of bulk Cu) was
      obtained by an IPL sintering process of 0.26 s after the printing, which was
      composed of 2 ms triple pulses with 10 Hz frequency. 

PMID- 24433058
TI  - The extent of inferior displacement of the mastoid tegmen is related to the
      severity of congenital aural atresia.
AB  - CONCLUSION: The extent of inferior displacement of the mastoid tegmen is related
      to the severity of congenital aural atresia (CAA). OBJECTIVE: To analyze anatomic
      variations observed on high-resolution temporal bone computed tomography (TBCT)
      in patients with CAA, the extent of inferior displacement of the mastoid tegmen
      and the size of the incudo-stapedial (IS) joint angle were compared with surgical
      parameters for atresiaplasty, such as Jahrsdoerfer score and hearing acuity.
      METHODS: Sixty-one patients with unilateral CAA underwent high-resolution TBCT
      and hearing tests. We evaluated TBCTs in terms of Jahrsdoerfer criteria and
      analyzed the relationships among the inferior displacement of the mastoid tegmen,
      size of the IS joint angle, hearing acuity, and the Jahrsdoerfer score on the
      atretic side. RESULTS: IS joint angle on the atretic side was found to be 120.6
      +/- 11 degrees , which was significantly greater than the corresponding value of
      103.4 +/- 5.4 degrees  on the normal side. Cholesteatoma occurred significantly
      more often in CAA patients with narrow external auditory canals (EACs) (9/27;
      33.3%), compared with CAA patients with no EAC opening (2/34; 5.9%). There was a
      significant relation between the extent of inferior displacement of the mastoid
      tegmen (28.9% in the atretic side and 17.3% in the normal side) and the
      Jahrsdoerfer score (p < 0.0001).

PMID- 24433061
TI  - Effects of aliskiren on blood pressure and humoral factors in hypertensive
      hemodialysis patients previously on angiotensin II receptor antagonists.
AB  - BACKGROUND: A direct renin inhibitor (DRI), aliskiren, may be effective for blood
      pressure (BP) control in hemodialysis patients. However, it is unclear whether
      aliskiren has a greater beneficial effect on BP and humoral factors than
      angiotensin II receptor antagonists (ARBs) in hypertensive patients on
      hemodialysis. METHODS: Eighteen hemodialysis patients (58 +/- 14 years) on the
      recommended dose of an ARB were prospectively randomized into two groups: ARB and
      DRI groups. Patients in the ARB group continued taking their previous ARB,
      whereas those in the DRI group switched to aliskiren (150 mg/day) for 12 weeks.
      Baseline measurements of BP and humoral factors such as plasma renin activity
      (PRA), plasma aldosterone concentration (PAC) and brain natriuretic peptide (BNP)
      were performed. Measurements were repeated every 4 weeks. RESULTS: At baseline,
      no differences were observed in age, gender or BP between the two groups.
      Systolic BP was unaffected by treatment in either groups (group effect, p = 0.26;
      time effect, p = 0.38; group * time effect, p = 0.24). PRA decreased in DRI (p <=
      0.02, group effect, p = 0.65; time effect, p = 0.13; group * time effect, p =
      0.048), but not in ARB (p >= 0.94). PAC increased only in DRI (p <= 0.03),
      whereas BNP was unaffected in either group. CONCLUSION: Aliskiren at a dose of
      150 mg/day had a similar effect on BP compared with ARBs, but significantly
      lowered PRA.

PMID- 24433062
TI  - Reappearance of Mecistocirrus digitatus in cattle from the Mexican tropics:
      prevalence, molecular, and scanning electron microscopy identification.
AB  - Mecistocirrus digitatus is a hematophagous abomasal nematode which causes
      significant blood and production losses in cattle. The objectives of the present
      study were to: (1) report the reappearance of M. digitatus in cattle from the
      Mexican tropics using microscopy, scanning electron microscopy (SEM), and
      molecular identification, and (2) determine the prevalence of M. digitatus in
      slaughtered adult cattle from the Mexican tropics. Gastroinestinal nematodes
      (GIN) were recovered from the abomasum of an 8-yr-old cow (Holstein * Zebu)
      previously diagnosed with Johne's disease. Of 1,254 GIN, 98.8% were identified as
      M. digitatus and 1.2% as Haemonchus sp. SEM was used to identify ultrastructure
      features of M. digitatus (oral cavity, cervical papillae, bursa, bursa lobes
      papillae, male spicules, anus, and female vulva). A conventional PCR method was
      used to corroborate the morphological findings. The prevalence of adult cattle
      infected with M. digitatus and Haemonchus sp., determined from 68 adult cattle
      from different grazing tropical herds, was 38.2% and 8.8%, respectively. Ninety
      eight percent of animals infected with M. digitatus presented lesions in their
      abomasum such as mucosal inflammation, hemorrhage, and ulcers; some of them had
      necrosis. The current reappearance of M. digitatus in a Mexican herd suggests the
      possibility of an underestimated prevalence of this nematode amongst grazing
      cattle.

PMID- 24433067
TI  - Molecular umbrella conjugate for the ocular delivery of siRNA.
AB  - The synthesis, computer modeling, and biological activity of an octawalled
      molecular umbrella short interfacing RNA (siRNA) conjugate is described. This
      molecular umbrella-siRNA conjugate exhibited mRNA knockdown activity in vitro in
      the absence of a transfection reagent. Evaluation of this molecular umbrella
      conjugate in vivo, using the rat eye via intravitreal injection, resulted in
      sequence specific mRNA knockdown in the retina with no obvious signs of toxicity,
      as judged by ophthalmic examination. 

PMID- 24433068
TI  - Bioconcentration and metabolism of BDE-209 in the presence of titanium dioxide
      nanoparticles and impact on the thyroid endocrine system and neuronal development
      in zebrafish larvae.
AB  - Interactions between organic toxicants and nanoparticles (NPs) in the aquatic
      environment may modify toxicant bioavailability and consequently the toxicant's
      environmental fate and toxicity. Therefore, we investigated the influence of
      titanium dioxide NPs (nano-TiO2) on deca-BDE (BDE-209; a polybrominated diphenyl
      ether congener) bioconcentration, metabolism and its effects on the thyroid
      endocrine system in zebrafish (Danio rerio) larvae. Zebrafish embryos were
      exposed to various concentrations of BDE-209 alone or in combination with nano
      TiO2 (0.1 mg/L) until 7-day post-fertilization. Nano-TiO2 can adsorb BDE-209 and
      nano-TiO2 is taken up into developing zebrafish larvae. Chemical measurements
      showed that BDE-209 was bioconcentrated and metabolized in zebrafish larvae, and
      BDE-209 uptake was enhanced by nano-TiO2. Furthermore, increased BDE-209
      metabolites were detected in larvae co-exposed with nano-TiO2. BDE-209 exposure
      significantly increased whole-body thyroid hormone contents (T3 and T4); T4
      content significantly increased in the larvae co-exposed with nano-TiO2. Nano
      TiO2 exposure alone did not induce generation of reactive oxygen species, lipid
      peroxidative oxidation, gene transcription or thyroid hormone levels.
      Upregulation of several gene transcriptions (tshbeta, tg, dio2) in the
      hypothalamic-pituitary-thyroid axis was also observed. Furthermore, co-exposure
      of nano-TiO2 and BDE-209 caused a decrease in locomotion activity and
      downregulation of specific genes and proteins involved in the central nervous
      system of developing zebrafish larvae (e.g. myelin basic protein and alpha1
      tubulin). These results indicate nano-TiO2 enhances BDE-209 bioavailability and
      metabolism, leading to thyroid endocrine disruption and developmental
      neurotoxicity in zebrafish.

PMID- 24433069
TI  - Inhibition of angiotensin-1-converting enzyme activity by two varieties of ginger
      (Zingiber officinale) in rats fed a high cholesterol diet.
AB  - Angiotensin-1-converting enzyme (ACE) inhibitors are widely used in the treatment
      of cardiovascular diseases. This study sought to investigate the inhibitory
      effect of two varieties of ginger (Zingiber officinale) commonly consumed in
      Nigeria on ACE activity in rats fed a high cholesterol diet. The inhibition of
      ACE activity of two varieties of ginger (Z. officinale) was investigated in a
      high cholesterol (2%) diet fed to rats for 3 days. Feeding high cholesterol diets
      to rats caused a significant (P<.05) increase in the ACE activity. However, there
      was a significant (P<.05) inhibition of ACE activity as a result of
      supplementation with the ginger varieties. Rats that were fed 4% white ginger had
      the greatest inhibitory effect as compared with a control diet. Furthermore,
      there was a significant (P<.05) increase in the plasma lipid profile with a
      concomitant increase in malondialdehyde (MDA) content in rat liver and heart
      tissues. However, supplementing the diet with red and white ginger (either 2% or
      4%) caused a significant (P<.05) decrease in the plasma total cholesterol,
      triglyceride, very low density lipoprotein-cholesterol, and low-density
      lipoprotein-cholesterol levels, and in MDA content in the tissues. Conversely,
      supplementation caused a significant (P<.05) increase in plasma high-density
      lipoprotein-cholesterol level when compared with the control diet. Nevertheless,
      rats fed 4% red ginger had the greatest reduction as compared with control diet.
      In conclusion, both ginger varieties exhibited anti-hypercholesterolemic
      properties in a high cholesterol diet fed to rats. This activity of the gingers
      may be attributed to its ACE inhibitory activity. However, white ginger inhibited
      ACE better in a high cholesterol diet fed to rats than red ginger. Therefore,
      both gingers could serve as good functional foods/nutraceuticals in the
      management/treatment of hypertension and other cardiovascular diseases.

PMID- 24433070
TI  - Antiobesity and vasoprotective effects of resveratrol in apoE-deficient mice.
AB  - This study was performed to investigate the hypolipidemic, antiobese, and
      antiatherogenic effects of resveratrol in apoE-deficient mice fed an atherogenic
      diet (20% fat and 1% cholesterol). These animals were fed an atherogenic diet
      containing 0.02% lovastatin (w/w) or 0.02% resveratrol (w/w) for 12 weeks.
      Resveratrol and lovastatin supplementation significantly reduced either the body
      weight or epididymal fat weight without altering the food intake and food
      efficiency ratio. Resveratrol significantly decreased the plasma total
      cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), non-high
      density lipoprotein cholesterol (non-HDL-C) concentrations, apoB/apoA-I ratio,
      hepatic cholesterol, and triglyceride (TG) contents, whereas significantly it
      increased the plasma HDL-C concentration compared with the control and lovastatin
      groups. Plasma and hepatic TG and plasma apoB levels were significantly lower in
      both the lovastatin and resveratrol groups than in the control group without
      altering the plasma apoA-I concentration. Both resveratrol and lovastatin
      significantly decreased hepatic fatty acid and TG synthesis, whereas they
      increased fatty acid oxidation (beta-oxidation) except for the carnitine
      palmitoyltransferase activity compared with the control group. However, there was
      no difference in hepatic 3-hydroxyl-3-methylglutaryl-CoA reductase activity among
      the groups, although hepatic acyl-CoA: cholesterol acyltransferase activity was
      significantly lower in the lovastatin groups than in the control group. In
      epididymal adipose tissue, resveratrol supplementation led to an increase in beta
      oxidation and decrease in TG synthesis, compared with the control group. Tissue
      morphology revealed that there were dramatic decreases in hepatic lipid droplets
      and aortic fatty streaks by resveratrol and lovastatin supplementation. This
      study demonstrates that resveratrol exerts not only antiobesity and hypolipidemic
      effects, but also protective effects for the liver and aorta through the
      modulation of lipid metabolism in both the liver and white adipose tissues.

PMID- 24433071
TI  - Agaricus brasiliensis KA21 improves circulatory functions in spontaneously
      hypertensive rats.
AB  - The present study aimed to clarify the effects of Agaricus brasiliensis KA21
      (i.e., Agaricus blazei) mushroom on circulatory function. Spontaneously
      hypertensive rats (SHRs) were fed 10% A. blazei-containing pellets (agaricus
      group) or normal pellets (control group) for 5 weeks from 6 to 11 weeks of age.
      For Experiment 1, tail blood pressure and heart rate were measured in the
      conscious SHRs. For Experiment 2, echocardiographic and blood biochemical
      measurements were performed in the anesthetized SHRs. In Experiment 1, blood
      pressure and heart rate were significantly lower in the agaricus group compared
      with the control group throughout the observation period. In Experiment 2, the
      agaricus group also showed a significant decrease in cardiac output accompanied
      by a decrease in heart rate and an increase in early and late ventricular filling
      velocity (E/A ratio). Moreover, levels of escape enzymes such as creatine kinase
      (CK), CK-BB, CK-MB, asparate aminotransferase, lactate dehydrogenase, and
      aldolase were significantly lower than in the control group. We concluded that
      the ingestion of feed containing A. brasiliensis KA21 can improve hypertensive
      cardiovascular hemodynamics by decreasing the working load of the heart,
      presumably by lowering the sympathetic nervous tone in SHRs.

PMID- 24433073
TI  - Feijoa sellowiana Berg fruit juice: anti-inflammatory effect and activity on
      superoxide anion generation.
AB  - Feijoa sellowiana Berg var. coolidge fruit juice was studied in vivo for the anti
      inflammatory activity by carrageenin-induced paw edema test and in vitro for the
      effects on superoxide anion release from neutrophils in human whole blood. The
      fruit juice was analyzed by the high-performance liquid chromatography method,
      and quercetin, ellagic acid, catechin, rutin, eriodictyol, gallic acid,
      pyrocatechol, syringic acid, and eriocitrin were identified. The results showed a
      significant anti-inflammatory activity of F. sellowiana fruit juice, sustained
      also by an effective antioxidant activity observed in preliminary studies on 1,1
      diphenyl-2-picrylhydrazyl (DPPH) test. In particular, the anti-inflammatory
      activity edema inhibition is significant since the first hour (44.11%) and
      persists until the fifth hour (44.12%) of the treatment. The effect on superoxide
      anion release was studied in human whole blood, in the presence of activators
      affecting neutrophils by different mechanisms. The juice showed an inhibiting
      response on neutrophils basal activity in all experimental conditions. In
      stimulated neutrophils, the higher inhibition of superoxide anion generation was
      observed at concentration of 10(-4) and 10(-2) mg/mL in whole blood stimulate
      with phorbol-myristate-13-acetate (PMA; 20% and 40%) and with N-formyl-methionyl
      leucyl-phenylalanine (FMLP; 15% and 48%). The significant reduction of edema and
      the inhibition of O2(-) production, occurring mainly through interaction with
      protein-kinase C pathway, confirm the anti-inflammatory effect of F. sellowiana
      fruit juice.

PMID- 24433072
TI  - Citric acid effects on brain and liver oxidative stress in lipopolysaccharide
      treated mice.
AB  - Citric acid is a weak organic acid found in the greatest amounts in citrus
      fruits. This study examined the effect of citric acid on endotoxin-induced
      oxidative stress of the brain and liver. Mice were challenged with a single
      intraperitoneal dose of lipopolysaccharide (LPS; 200 MUg/kg). Citric acid was
      given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were
      euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue,
      resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and
      nitrite, while significantly decreasing reduced glutathione, glutathione
      peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha
      (TNF-alpha) showed a pronounced increase in brain tissue after endotoxin
      injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced
      elevations in brain MDA, nitrite, TNF-alpha, GPx, and PON1 activity. In the
      liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased,
      while PON1 activity was decreased by citric acid. The LPS-induced liver injury,
      DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric
      oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA
      fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of
      systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation
      and inflammation, liver damage, and DNA fragmentation.

PMID- 24433074
TI  - Inhibition of nonenzymatic protein glycation by pomegranate and other fruit
      juices.
AB  - The nonenzymatic glycation of proteins and the formation of advanced glycation
      endproducts in diabetes leads to the crosslinking of proteins and disease
      complications. Our study sought to demonstrate the effect of commonly consumed
      juices (pomegranate, cranberry, black cherry, pineapple, apple, and Concord
      grape) on the fructose-mediated glycation of albumin. Albumin glycation decreased
      by 98% in the presence of 10 MUL of pomegranate juice/mL; other juices inhibited
      glycation by only 20%. Pomegranate juice produced the greatest inhibition on
      protein glycation when incubated at both the same phenolic concentration and the
      same antioxidant potential. Both punicalagin and ellagic acid significantly
      inhibited the glycation of albumin by ~90% at 5 MUg/mL. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed that pomegranate, but not apple
      juice, protected albumin from modification. These results demonstrate that
      pomegranate juice and two of its major constituents are potent inhibitors of
      fructose-mediated protein glycation.

PMID- 24433075
TI  - Probiotic screening and safety evaluation of Lactobacillus strains from plants,
      artisanal goat cheese, human stools, and breast milk.
AB  - The aim of this study was to select autochthonous strains of Lactobacillus from
      stools of healthy infants and adults, human milk, artisanal goat cheese, and
      fruits and vegetables according to their probiotic properties and safety. From
      421 strains of Lactobacillus isolated, 102 (24.2%) were shown to be tolerant to
      gastric pH and bile salts; they were used to determine their anti-Helicobacter
      pylori (agar diffusion assay), antioxidant (oxygen radical absorption capacity),
      and anti-inflammatory (inhibition of interleukin-8 release by tumor necrosis
      factor-alpha-stimulated HT-29 cells) activities as well as their ability to
      adhere to intestinal (Caco-2) and gastric (AGS) epithelial cells. Results
      obtained were compared with three commercial probiotic Lactobacillus rhamnosus
      GG, L. plantarum 299v, and L. johnsonii NCC533. The five strains most efficient
      according to these activities were subsequently identified by sequencing their
      16S rRNA gene, their susceptibility to antibiotics was determined, and their
      safety evaluated in mice. One strain of L. plantarum was discarded due to the
      higher prevalence of liver bacterial translocation observed in the animals fed
      this strain. In conclusion, four autochthonous strains of L. rhamnosus were
      finally selected with probiotic properties and safety allowing their eventual use
      in human studies. These results contribute to increase the diversity of probiotic
      strains available for the development of nutraceuticals and functional foods.

PMID- 24433076
TI  - Dietary supplementation with polyphenol-rich chokeberry juice improves skin
      morphology in cellulite.
AB  - The aim of our study was to investigate possible beneficial effects of organic
      chokeberry juice (OCJ) consumption in the treatment of cellulite. Twenty-nine
      women aged 25-48 with a cellulite grade 2 according to the Nurnberger-Muller
      scale were included. Anthropometric and biochemical parameters were measured.
      Skin structure was analyzed by ultrasonography. All subjects consumed 100 mL of
      OCJ per day, during 90 days. Measurements of investigated parameters were
      performed at 0, 45, and 90 days of the study. A marked reduction in the
      subcutaneous tissue thickness was observed in all subjects, with the average
      reduction of 1.9 mm. The length of subcutaneous tissue fascicles (ScTFL) was
      reduced in 97% (28 out of 29) of subjects, with the average value of 1.18 mm.
      After 45 days of chokeberry juice consumption, reduction of edema was observed in
      55.2% of the subjects with edema at the baseline, while at the endpoint of the
      study, edemas were not observed in any of the subjects involved in the study. OCJ
      could have beneficial effects on the cellulite condition, including the length of
      ScTFL, subcutaneous tissue, and dermis thickness as well as on edema reduction.

PMID- 24433077
TI  - Evaluation of antiradical activity of different cocoa and chocolate products:
      relation with lipid and protein composition.
AB  - Chocolate antioxidant properties are often claimed; however, they are frequently
      different from the parent natural sources due to the industry or artisan
      transformation. In particular, antioxidant property of chocolate and cocoa are
      not adequately taken into consideration by consumers who normally make use of
      this food just for its flavor and taste properties. In this study, we have
      investigated the antioxidant capacity and total phenolic content of cocoa nibs,
      cocoa masses, and corresponding chocolate bars with different percentages of
      cocoa from different origins. The antioxidant capacity of the different samples
      was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical
      (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin
      Ciocalteu reagent was used to assess the total phenolic content. The masses
      showed a higher antioxidant power than the nibs, and this has been attributed to
      the fact that in the nibs is still present the lipid part, which will form the
      cocoa butter. The influence of milk, whey, and soy proteins was also
      investigated. Our results showed that the extra dark cocoa bar, 100% cocoa
      chocolate, is the best in terms of total polyphenol content and in terms of
      antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars
      of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are
      well performing in all respects. As highlighted by us, the antiradical properties
      of cocoa products are higher than many antioxidant supplements in tablets.

PMID- 24433078
TI  - An overview on cardamonin.
AB  - Cardamonin, as shown by the increasing number of publications, has received
      growing attention from the scientific community due to the expectations toward
      its benefits to human health. In this study, research on cardamonin is reviewed,
      including its natural sources, health promoting aspects, and analytical methods
      for its determination. Therefore, this article hopes to aid current and future
      researchers on the search for reliable answers concerning cardamonin's value in
      medicine.

PMID- 24433082
TI  - Loss of bone morphogenetic protein receptor 2 is associated with abnormal DNA
      repair in pulmonary arterial hypertension.
AB  - Occlusive vasculopathy with intimal hyperplasia and plexogenic arteriopathy are
      severe histopathological changes characteristic of pulmonary arterial
      hypertension (PAH). Although a phenotypic switch in pulmonary endothelial cells
      (ECs) has been suggested to play a critical role in the formation of occlusive
      lesions, the pathobiology of this process is poorly understood. The goal of this
      study was to identify novel molecular mechanisms associated with EC dysfunction
      and PAH-associated bone morphogenetic protein receptor 2 (BMPR2) deficiency
      during PAH pathogenesis. A bioinfomatics approach, patient samples, and in vitro
      experiments were used. By combining a metaanalysis of human idiopathic PAH (iPAH)
      associated gene-expression microarrays and a unique gene expression-profiling
      technique in rat endothelium, our bioinformatics approach revealed a PAH
      associated dysregulation of genes involving chromatin organization, DNA
      metabolism, and repair. Our hypothesis that altered DNA repair and loss of
      genomic stability play a role in PAH was supported by in vitro assays where
      pulmonary ECs from patients with iPAH and BMPR2-deficient ECs were highly
      susceptible to DNA damage. Furthermore, we showed that BMPR2 expression is
      tightly linked to DNA damage control because excessive DNA damage leads to rapid
      down-regulation of BMPR2 expression. Moreover, we identified breast cancer 1
      (BRCA1) as a novel target for BMPR2 signaling and a novel modulator of pulmonary
      EC homeostasis. We show here that BMPR2 signaling plays a critical role in the
      regulation of genomic integrity in pulmonary ECs via genes such as BRCA1. We
      propose that iPAH-associated EC dysfunction and genomic instability are mediated
      through BMPR2 deficiency-associated loss of DNA damage control. 

PMID- 24433083
TI  - Development and validation of the Spanish Hazard Perception Test.
AB  - OBJECTIVE: The aim of the current study is to develop and obtain valid evidence
      for a hazard perception test suitable for the Spanish driving population. To
      obtain valid evidence to support the use of the test, the effect of hazardous and
      quasi-hazardous situations on the participants' hazard prediction is analyzed and
      the pattern of results for drivers with different driving experience--that is,
      learner, novice, and expert drivers and reoffender vs. nonoffender drivers--is
      compared. Potentially hazardous situations are those that develop without
      involving any real hazard (i.e., the driver did not actually have to decelerate
      or make any evasive maneuver to avoid a potential collision). The current study
      analyzed repeat offender drivers attending compulsory reeducation programs as a
      result of reaching the maximum number of penalty points on their driving license
      due to repeated violations of traffic laws. METHOD: A new video-based hazard
      perception test was developed, using a total of 20 hazardous situation videos
      plus 8 quasi-hazardous situation videos. They were selected from 167 recordings
      of natural hazards in real Spanish driving settings. RESULTS: The test showed
      adequate psychometric properties and evidence of validity, distinguishing between
      different types of drivers. Psychometric results confirm a final version of the
      hazard perception test composed of 11 video clips of hazards and 6 video clips of
      quasi-hazards, for which an overall Cronbach's alpha coefficient of.77 was
      obtained. A lack of ability to detect quasi-hazards and distinguish them from
      hazardous situations was also found for learner, novice, and reoffender drivers.
      Learner drivers obtained lower average scores than novice and experienced drivers
      with the hazardous situation videos, and learner drivers obtained lower average
      scores than experienced drivers with the quasi-hazardous situation videos,
      suggesting that the ability to correctly identify hazardous traffic situations
      may develop early by accumulating initial driving experience. However, the
      ability to correctly identify quasi-hazardous situations may develop later with
      the accumulation of further driving experience. Developing this ability is also
      difficult for reoffender drivers. CONCLUSION: The test has adequate psychometric
      properties and is useful in distinguishing between learner, novice, and expert
      drivers. In addition, it is useful in that it analyzes the performance of both
      safe and unsafe drivers (reoffenders who have already lost their driving
      license).

PMID- 24433086
TI  - One-step carbonization synthesis of hollow carbon nanococoons with multimodal
      pores and their enhanced electrochemical performance for supercapacitors.
AB  - Hollow carbon capsules with multimodal pores are highly promising for developing
      novel electrode materials for high-performance electrochemical devices due to
      their more active sites for ion and electron transfer. However, at present, most
      of the previous efforts are focused on the multistep process for the synthesis of
      hollow carbon nanostructures with individual pores. Herein, hollow carbon
      nanococoons (HCNCs) with non-spherical cavity and multimodal hierarchical pores
      have been facilely synthesized via a one-step carbonization of a Fe2O3/carbon
      precursor core/shell nanospindle at 850  degrees C. We interestingly found that
      during the carbonization, Fe2O3 was automatically "escaped" from the inside
      nanospindle, leading to the formation of new HCNCs. Most importantly, the spindle
      shaped cavity of the obtained HCNCs with high conductivity can offer a multimodal
      ion diffusion pathway, which can facilitate the reaction kinetics in a
      supercapacitor. As a result, the HCNCs-based supacapacitor exhibits the
      capacitance of 220.0 F g(-1) at a given scan rate of 5 mV s(-1), 3.5 times higher
      than that of hollow carbon spheres, high stability with 98% of the initial
      capacity maintained even after 1000 cycles, and high rate capability. This work
      provides a new and facile avenue for enhancing performance of a HCNCs-based
      supercapacitor by using the non-spherical hollow structures with multimodal
      pores. 

PMID- 24433087
TI  - Gold nanowire based electrical DNA detection using rolling circle amplification.
AB  - We present an electrical sensor that uses rolling circle amplification (RCA) of
      DNA to stretch across the gap between two electrodes, interact with metal
      nanoparticle seeds to generate an electrically conductive nanowire, and produce
      electrical signals upon detection of specific target DNA sequences. RCA is a
      highly specific molecular detection mechanism based on DNA probe circularization.
      With this technique, long single-stranded DNA with simple repetitive sequences
      are produced. Here we show that stretched RCA products can be metalized using
      silver or gold solutions to form metal wires. Upon metallization, the resistance
      drops from TOmega to kOmega for silver and to Omega for gold. Metallization is
      seeded by gold nanoparticles aligned along the single-stranded DNA product
      through hybridization of functionalized oligonucleotides. We show that combining
      RCA with electrical DNA detection produces results in readout with very high
      signal-to-noise ratio, an essential feature for sensitive and specific detection
      assays. Finally, we demonstrate detection of 10 ng of Escherichia coli genomic
      DNA using the sensor concept. 

PMID- 24433088
TI  - Management of bone disease in multiple myeloma.
AB  - Osteolytic bone disease is the most common complication of multiple myeloma,
      resulting in skeletal complications that cause significant morbidity and
      mortality. Currently, bisphosphonates (BPs) are the mainstay for the treatment of
      myeloma bone disease. Zoledronic acid which has been found to be superior to
      clodronate, both in terms of reduction of skeletal-related events (SREs) and
      survival, and pamidronate are used for the management of myeloma-related bone
      disease. Patients with active disease (not in CR or VGPR) should receive BPs
      (especially zoledronic acid) even after two years of administration. Radiotherapy
      and surgical interventions can also be used for specific conditions, such as
      pathological fractures, spinal cord compression or uncontrolled pain. The better
      understanding of the biology of myeloma bone disease has led to the production of
      several novel agents, such as denosumab (targeting RANKL), sotatercept (activin-A
      antagonist) and romosozumab (targeting sclerostin) that appear very promising and
      have entered to clinical development. 

PMID- 24433089
TI  - The 5-HTTLPR polymorphism, early and recent life stress, and cognitive
      endophenotypes of depression.
AB  - Studies associating interactions of 5-HTTLPR and life adversities with depression
      have yielded equivocal results. Studying endophenotypes may constitute a more
      powerful approach. In the current study, it was assessed whether interactions of
      5-HTTLPR with childhood emotional abuse (CEA) and recent negative life events
      (RNLE) affect possible cognitive endophenotypes of depression, namely, attention
      allocation bias and the ability to recognise others' mind states in 215 young
      adults of North-West European descent. The ability to classify others' negative
      mind states was found to be increased with increasing RNLE in carriers of low
      expressing Serotonin Transporter Linked Polymorphic Region (5-HTTLPR) alleles.
      Carriers of two low-expressing alleles also preferentially oriented attention
      towards negative information. Gene-environment interactions were not observed for
      attention allocation bias. No effects involving CEA were observed. These results
      suggest that low-expressing 5-HTTLPR alleles may confer increased risk for
      depression through enhanced recognition of negative facial expressions following
      RNLE. 

PMID- 24433091
TI  - New inflammatory markers in pre-eclampsia: echocardiographic epicardial fat
      thickness and neutrophil to lymphocyte ratio.
AB  - BACKGROUND: Increased epicardial fat thickness (EFT) has been proposed as a new
      cardiometabolic risk factor. The neutrophil/lymphocyte ratio (NLR) has predictive
      and prognostic value in several cardiovascular diseases. The aim of this study
      was to explore the association between EFT and NLR in patients with pre
      eclampsia. METHODS: Hundred and eight pregnant patients with a mean age of 30.6
      +/- 6.3 years were included in the study. Patients were divided into two groups
      based on the presence of pre-eclampsia. All participants underwent transthoracic
      echocardiography imaging, and complete blood counts were measured by an automated
      hematology analyzer. Statistical analysis was performed using the Chi-square,
      Mann-Whitney U, correlation and logistic regression tests, and receiver operating
      characteristic (ROC) analysis. RESULT: The mean EFT value of the pre-eclampsia
      group was significantly higher than the control group (6.9 +/- 0.6 versus 5.6 +/-
      0.6; p < 0.001), and the NLR value of the pre-eclampsia group was also
      significantly higher than the control group (7.3 +/- 3.5 versus 3.1 +/- 1.1; p <
      0.001). Multivariate analysis showed that increased levels of NLR and
      echocardiographic EFT are independent predictors of pre-eclampsia. In the
      receiver operating characteristic analysis, a level of EFT >= 6.2 mm and NLR >=
      4.1 predicted the presence of pre-eclampsia with 77.8% sensitivity, 79.6%
      specificity and 83.3% sensitivity, 81.5% specificity, respectively. CONCLUSION:
      Unlike many other inflammatory markers and bioassays, NLR and echocardiographic
      EFT are inexpensive and readily available biomarkers that may be useful for risk
      stratification in patients with pre-eclampsia.

PMID- 24433093
TI  - Interhemispheric cooperation in global-local visual processing in pediatric
      multiple sclerosis.
AB  - Impairments in visuospatial abilities are commonly reported in children and
      adolescents with multiple sclerosis (MS). Corpus callosum (CC) pathology occurs
      in patients with MS and may contribute to impairment in visuospatial perception,
      particularly when interhemispheric information transfer is required. This study
      used a global-local hierarchical letter paradigm to examine the relationship
      between interhemispheric information transfer and white matter integrity in the
      CC assessed using diffusion tensor imaging. Thirteen cognitively preserved
      pediatric-onset MS patients and 15 age-matched healthy controls were asked to
      determine whether a target letter E appeared at the attended level of the
      stimulus. As expected, both groups processed global and local information more
      slowly under divided than selective attention conditions. The MS group performed
      similarly to the control group with respect to reaction time and accuracy on
      selective and divided attention conditions, with one exception. Specifically, the
      presence of a global target when attending to a local target caused greater
      response conflict in the MS group than in controls (p = .01). Pooling both the
      patient and control data, greater response conflict was associated with reduced
      white matter integrity as indicated by lower fractional anisotropy in the
      anterior body of the CC (r = -.33, p < .05). Results suggest that reduced white
      matter integrity in anterior regions of the CC may lead to less efficient
      inhibition of task-irrelevant global information in the hierarchal processing of
      visual information. 

PMID- 24433094
TI  - Expression of microRNA-93 and Interleukin-8 during Pseudomonas aeruginosa
      mediated induction of proinflammatory responses.
AB  - In this study we analyzed the microRNA profile of cystic fibrosis (CF) bronchial
      epithelial IB3-1 cells infected with Pseudomonas aeruginosa by microarray and
      quantitative RT-PCR, demonstrating that microRNA 93 (miR-93), which is highly
      expressed in basal conditions, decreases during infection in parallel with
      increased expression of the IL-8 gene. The down-regulation of miR-93 after P.
      aeruginosa infection was confirmed in other bronchial cell lines derived from
      subjects with and without CF, namely CuFi-1 and NuLi-1 cells. Sequence analysis
      shows that the 3'-UTR region of IL-8 mRNA is a potential target of miR-93 and
      that the consensus sequence is highly conserved throughout molecular evolution.
      The possible involvement of miR-93 in IL-8 gene regulation was validated using
      three luciferase vectors, including one carrying the complete 3'-UTR region of
      the IL-8 mRNA and one carrying the same region with a mutated miR-93 site. Up
      modulation of IL-8 after P. aeruginosa infection was counteracted in IB3-1, CuFi
      1, and NuLi-1 cells by pre-miR-93 transfection. In addition, IL-8 was up
      regulated in uninfected cells treated with antagomiR-93. Our results support the
      concept of a possible link between microRNA expression and IL-8 induction in
      bronchial epithelial cells infected with P. aeruginosa. Specifically, the data
      presented here indicate that, in addition to NF-kappaB-dependent up-regulation of
      IL-8 gene transcription, IL-8 protein expression is posttranscriptionally
      regulated by interactions of the IL-8 mRNA with the inhibitory miR-93. 

PMID- 24433096
TI  - Dried umbilical cord is a potential material for retrospective diagnosis of
      intrauterine enterovirus infection.
AB  - OBJECTIVE: To determine whether dried umbilical cords (UCs) are useful for
      retrospective diagnosis of intrauterine enterovirus (EV) infection. METHODS:
      Dried UCs in two patients with neonatal EV sepsis and 10 neonates without
      infectious signs were enrolled. Viral RNA was extracted from their dried UCs, and
      nested reverse transcription polymerase chain reaction (RT-PCR) was performed.
      RESULTS: Infection routes estimated by the clinical course were intrauterine
      infection in Case 1 and post-natal horizontal infection in Case 2. EV-RNA was
      detected from dried UC in Case 1, but not in Case 2 and 10 neonates. CONCLUSIONS:
      This report showed the potential use of dried UCs for retrospective diagnosis of
      intrauterine EV infection.

PMID- 24433095
TI  - (64)Cu-labeled LyP-1-dendrimer for PET-CT imaging of atherosclerotic plaque.
AB  - The ability to detect and quantify macrophage accumulation can provide important
      diagnostic and prognostic information for atherosclerotic plaque. We have
      previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins
      on activated macrophages, facilitating the visualization of atherosclerotic
      plaque with PET. Yet, the in vivo plaque accumulation of monomeric [(18)F]FBA-LyP
      1 was low (0.31 +/- 0.05%ID/g). To increase the avidity of LyP-1 constructs to
      p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the
      core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a
      lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus
      of the dendrimer was further modified with an aminooxy group in order to
      conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to
      both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM)
      and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT
      were labeled with (64)Cu (t1/2 = 12.7 h) and intravenously injected into the
      atherosclerotic (ApoE(-/-)) mice. After two hours of circulation, PET-CT
      coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-(64)Cu
      than the (ARAL)4-dendrimer-(64)Cu in the aortic root and descending aorta. Ex
      vivo images and the biodistribution acquired at three hours after injection also
      demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-(64)Cu (1.1
      +/- 0.26%ID/g) than the (ARAL)4-dendrimer-(64)Cu (0.22 +/- 0.05%ID/g) in the
      aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers
      resulted in preferential accumulation in plaque-containing regions over 24 h. In
      the same model system, ex vivo fluorescence images within aortic plaque depict an
      increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared
      to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP
      1)4-dendrimer can be applied for in vivo PET imaging of plaque and that LyP-1
      could be further exploited for the delivery of therapeutics with multivalent
      carriers or nanoparticles. 

PMID- 24433100
TI  - Nanocomposite gels via in situ photoinitiation and disassembly of TiOTiO2-clay
      composites with polymers applied as UV protective films.
AB  - We report a facile solution polymerized approach to prepare nanocomposite
      hydrogels. The electrostatic assembly of positive TiO2 nanoparticles with
      negative clay nanosheets obtained TiO2-clay composite particles, which was
      disassembled by the solution polymerization of N,N-dimethylacrylamide and
      homogeneously interacted with poly(N,N-dimethylacrylamide) chain to form
      nanocomposite hydrogels. The final nanocomposite hydrogels are mechanical tough
      and transparent, which has the maximum 598.21 KPa compressive strength. The
      immobilized TiO2 not only acted as the photo-initiator for radical polymerization
      but also endowed the nanocomposite gel films good UV protective performance. This
      strategy can be very useful for preparing nanocomposite hydrogels with different
      functions. 

PMID- 24433103
TI  - Influence of a combo side airbag on the risk for basilar skull fracture in a far
      side occupant.
AB  - OBJECTIVE: The impact force to the head and neck were measured in sled tests with
      and without inflation of a combo airbag for a far-side occupant to determine the
      risk for basilar skull fracture. METHODS: Sled tests were run at 24 and 32 km/h
      (15 and 20 mph) with and without inflation of a combo side airbag to analyze the
      effect of cross-car diving into the side interior. The matched tests involved one
      pair at 24 km/h and another at 32 km/h. The 24 km/h pair involved a lap-shoulder
      belted 5th percentile female Hybrid III and the series at 32 km/h involved an
      unbelted 5th percentile Hybrid III. The dummy was ballasted to 69.5 kg (153 lb)
      and laid on the right side. The dummy was positioned 30.5 cm (12(")) from the far
      side interior to ensure the full sled delta V occurred before head impact. The
      buck consisted of a 2001 Ford Taurus. The combo thorax-head side airbag was
      stored in the seatback. The airbag was triggered about 120 ms before the head
      impact. The head, chest, and pelvis were instrumented with triaxial
      accelerometers and the upper and lower neck, thoracic spine, and lumbar spine had
      transducers measuring triaxial loads and moments. High-speed video recorded
      different views of the dummy motion. Dummy kinematics and biomechanical responses
      were compared to study the influence of inflating the side airbag on the head and
      neck. RESULTS: The top of the head impacted the far side. The force of impact was
      similar with and without the airbag as the head compressed the airbag and loaded
      the vehicle interior trim behind the airbag. The peak force on the head was
      primarily from neck load as torso augmentation occurred. For the 24 km/h (15 mph)
      tests, the peak force was 4.7 kN (1055 lb) without and 4.8 kN (1088 lb) with the
      airbag and there was over 2.67 kN (600 lb) of lap belt load. The peak head
      acceleration was 93 g without and 72 g with the airbag. For the 32 km/h (20 mph)
      tests, the force on the head was 15.3 kN (3433 lb) without and 15.2 kN (3406 lb)
      with the airbag, although the instrumentation saturated. The peak head
      acceleration was 236 g without and 262 g with the airbag. CONCLUSION: The airbag
      reduced head acceleration in the belted test but did not influence the diving
      forces from torso augmentation through the neck of the far-side occupant. The
      side airbag did not reduce the risk for basilar skull fracture due to high neck
      compression loads in either the belted or unbelted tests.

PMID- 24433104
TI  - Medial epicanthoplasty using the "inside-out" technique.
AB  - The epicanthal fold, a skin remnant covering the medial canthal region, is
      especially common in Asians. Although numerous surgical techniques for the
      treatment of the epicanthal fold have been developed, the results.in terms of
      scars and a natural look remain controversial. In this regard, the authors have
      developed a new method for medial epicanthoplasty. From January 2005 to December
      2011, medial epicanthoplasty was performed on 1132 patients using a technique in
      which the skin flap inside of the medial epicanthal fold is moved outward (the
      "Inside-Out" technique). Preoperative and postoperative (2 months)
      interepicanthal distance was measured. Satisfactory results were achieved in the
      majority of cases. While nine patients complained of visible scarring after the
      operation, the scar formation spontaneously resolved within 6 months. This new
      "Inside-Out" technique for the treatment of the epicanthal fold is easy, simple,
      and delivers good aesthetic results.

PMID- 24433105
TI  - An overview of the progress in the treatment of multiple myeloma.
AB  - Effective therapy for multiple myeloma has existed for a little more than the
      last half century. The introduction of melphalan 55 years ago was followed by a
      stagnant period of four decades in which many combinations of alkylating agents
      and chemotherapeutic drugs were developed without a significant increase in
      overall survival. The first novel agent, thalidomide, was introduced 15 years ago
      when it was used as an anti-angiogenesis agent. This was followed by a proteasome
      inhibitor, bortezomib. Then lenalidomide, a second-generation analog of
      thalidomide was introduced. More recently carfilzomib, a proteasome inhibitor,
      and pomalidomide, a third-generation derivative of thalidomide have entered the
      marketplace. Many new agents are in development and potentially available for
      future therapy. 

PMID- 24433106
TI  - Experiments for the editing of singlet peaks and simplification of 1H NMR spectra
      of complex mixtures.
AB  - A 1D NMR singlet filtered experiment (s-filter) is presented for the clean
      editing of singlets peaks in crowded 1H NMR spectra. The experiment affords a
      clean editing of singlet peaks and weak coupled signals ((n)JHH < 3 Hz), while
      the remaining multiplets peaks are strongly attenuated to a factor over 90% of
      its original intensity. The experiment provided a useful simplification of the
      typically congested 1H NMR spectra of foodstuffs, and the edited signals retained
      most of the sensitivity and quantitativity. The versatility of the s-filter
      scheme permitted its easy incorporation as excitation building block into other
      1D and 2D experiments, providing a further editing of the singlet responses. The
      combination of the 1D s-filter experiment and difference spectroscopy provided a
      1D reverse singlet filtered experiment (s-filter(rev)) for the clean editing of
      multiplet peaks and strong suppression of singlets. The experiments proposed
      could be valuable to facilitate the detection and/or quantification of target
      compounds in complex mixtures of metabolites.

PMID- 24433108
TI  - Effectiveness of using long-acting angiotensin II type 1 receptor blocker in
      Japanese obese patients with metabolic syndrome on morning hypertension
      monitoring by using telemedicine system (FUJIYAMA study).
AB  - AIM: Recently, obesity patients have been diagnosed as metabolic syndrome. The
      aim of this study was to evaluate which angiotensin type 1 receptor blockers
      (ARBs), telmisartan or candesartan, is superior for the control of home blood
      pressure (BP) in the morning when the outpatient clinic BP was well controlled in
      the patients with metabolic syndrome. METHODS: The patients with metabolic
      syndrome were enrolled. Home BP was monitored by using a telemedicine system.
      After a 2- to 4-week control period to establish baseline home BP values, these
      patients were randomly divided into telmisartan (20-80 mg) and candesartan (4-12
      mg) groups. These end points were evaluated by using the telemedicine system
      during steady-state active therapy. A total of 356 patients attending 60
      outpatient Japanese centers were recruited. RESULTS: On a day of active therapy,
      telmisartan significantly lowered both systolic and diastolic home BP in the
      morning to a greater extent compared to candesartan. At the end of the study,
      reductions in systolic and diastolic home BP in the morning, in telmisartan group
      were significantly larger compared to the changes in the candesartan group
      (systolic; Tel: 12.0 +/- 8.9 versus Can: 8.1 +/- 17.1 mmHg, p = 0.0292,
      diastolic; Tel: 7.4 +/- 6.1 versus Can: 3.7 +/- 6.8 mmHg, p = 0.0053).
      Additionally in the telmisartan treated group, LDL-cholesterol showed significant
      reduction (p = 0.037), but candesartan did not. CONCLUSION: The present study by
      using the telemedicine system clearly demonstrated that telmisartan has a strong
      effect on reducing morning home BP, and a good effect on lipid metabolism in
      patients with metabolic syndrome.

PMID- 24433109
TI  - Recurrent hepatic hematoma due to familial lysozyme amyloidosis resolves with
      conservative management.

PMID- 24433110
TI  - Structural insights into the membrane fusion mechanism mediated by influenza
      virus hemagglutinin.
AB  - Membrane fusion is involved in many fundamental cellular processes and entry of
      enveloped viruses into host cells. Influenza type A virus HA has long served as a
      paradigm for mechanistic studies of protein-mediated membrane fusion via large
      scale structural rearrangements induced by acidic pH. Here we report the newly
      determined crystal structure of influenza B virus HA2 in the postfusion state.
      Together with a large number of previously determined prefusion structures of
      influenza A and B virus HA and a postfusion structure of influenza A/H3N2 HA2, we
      identified conserved features that are shared between influenza A and B virus HA
      in the conformational transition and documented substantial differences that
      likely influence the detailed mechanisms of this process. Further studies are
      needed to dissect the effects of these and other structural differences in HA
      conformational changes and influenza pathogenicity and transmission, which may
      ultimately expedite the discovery of novel anti-influenza fusion inhibitors. 

PMID- 24433111
TI  - Measuring the rate of fetal urine production using three-dimensional ultrasound
      during normal pregnancy and pregnancy-associated diabetes.
AB  - OBJECTIVE: To establish a nomogram of fetal urine production according to
      gestational age as a predictor for fetal well-being in normal and diabetic women.
      STUDY DESIGN: Prospective observational study included 180 pregnant women
      classified into two groups: Group I (120 women) without any medical complications
      and Group II (60 women) with gestational diabetes mellitus (GDM). The fetal
      bladder is measured by the virtual organ computer-aided analysis VOCAL 3D
      ultrasound scanner. RESULTS: There was a significant positive correlation between
      gestational age and fetal urine production rate (UPR) (the mean UPR rate in
      normal pregnancy at 25, 30, 35, 40 weeks were 12.3, 14.38, 56.13 and 90.73 ml/h,
      respectively). There was no significant difference regarding UPR ml/h between
      women with normal pregnancy and those with controlled GDM (p = 0.9). There was a
      statistically significant difference regarding UPR ml/h between women with normal
      pregnancy and those with uncontrolled GDM (p = 0.012) and a statistically
      significant difference between women with controlled GDM and those with
      uncontrolled GDM (p = 0.03). CONCLUSION: Fetal UPR is considered to be more
      reliable as an assessment method for fetal well-being and shows significant
      increase in patients with uncontrolled gestational DM.

PMID- 24433112
TI  - Self-assembly of colloidal hexagonal bipyramid- and bifrustum-shaped ZnS
      nanocrystals into two-dimensional superstructures.
AB  - We present a combined experimental, theoretical, and simulation study on the self
      assembly of colloidal hexagonal bipyramid- and hexagonal bifrustum-shaped ZnS
      nanocrystals (NCs) into two-dimensional superlattices. The simulated NC
      superstructures are in good agreement with the experimental ones. This shows that
      the self-assembly process is primarily driven by minimization of the interfacial
      free-energies and maximization of the packing density. Our study shows that a
      small truncation of the hexagonal bipyramids is sufficient to change the symmetry
      of the resulting superlattice from hexagonal to tetragonal, highlighting the
      crucial importance of precise shape control in the fabrication of functional
      metamaterials by self-assembly of colloidal NCs. 

PMID- 24433115
TI  - Comprehensive target populations for current active safety systems using national
      crash databases.
AB  - OBJECTIVE: The objective of active safety systems is to prevent or mitigate
      collisions. A critical component in the design of active safety systems is the
      identification of the target population for a proposed system. The target
      population for an active safety system is that set of crashes that a proposed
      system could prevent or mitigate. Target crashes have scenarios in which the
      sensors and algorithms would likely activate. For example, the rear-end crash
      scenario, where the front of one vehicle contacts another vehicle traveling in
      the same direction and in the same lane as the striking vehicle, is one scenario
      for which forward collision warning (FCW) would be most effective in mitigating
      or preventing. This article presents a novel set of precrash scenarios based on
      coded variables from NHTSA's nationally representative crash databases in the
      United States. METHODS: Using 4 databases (National Automotive Sampling System
      General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS],
      Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash
      Causation Survey [NMVCCS]) the scenarios developed in this study can be used to
      quantify the number of police-reported crashes, seriously injured occupants, and
      fatalities that are applicable to proposed active safety systems. In this
      article, we use the precrash scenarios to identify the target populations for
      FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and
      vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash
      scenarios were derived using precrash variables (critical event, accident type,
      precrash movement) present in all 4 data sources. RESULTS AND CONCLUSIONS: This
      study found that these active safety systems could potentially mitigate
      approximately 1 in 5 of all severity and serious injury crashes in the United
      States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million
      all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In
      addition, we provide the source code for the crash scenarios as an appendix (see
      online supplement) to this article so that researchers can use the crash
      scenarios in future research.

PMID- 24433116
TI  - Biocompatible and highly luminescent near-infrared CuInS2/ZnS quantum dots
      embedded silica beads for cancer cell imaging.
AB  - Bright and stable CuInS2/ZnS@SiO2 nanoparticles with near-infrared (NIR) emission
      were competently prepared by incorporating the as-prepared hydrophobic CuInS2/ZnS
      quantum dots (QDs) directly into lipophilic silane micelles and subsequently an
      exterior silica shell was formed. The obtained CuInS2/ZnS@SiO2 nanoparticles
      homogeneously comprised both single-core and multicore remarkable CuInS2/ZnS QDs,
      while the silica shell thickness could be controlled to within 5-10 nm and their
      overall size was 17-25 nm. Also, the functionalized CuInS2/ZnS QDs encapsulated
      in the silica spheres, expedited their bioconjugation with holo-Transferrin (Tf)
      for further cancer cell imaging. The CuInS2/ZnS@SiO2 nanoparticles not only
      showed a dominant NIR band-edge luminescence at 650-720 nm with a quantum yield
      (QY) between 30 and 50%, without a recognized photoluminescence (PL) red shift,
      but also exhibited excellent PL and colloidal stability in aqueous media.
      Impressively, the cytotoxicity studies revealed minor suppression on cell
      viability under both CuInS2/ZnS@SiO2 and CuInS2/ZnS@SiO2@Tf concentrations up to
      1 mg/mL. The application in live-cell imaging revealed that the potential of
      CuInS2/ZnS QDs as biocompatible, robust, cadmium-free, and brilliant NIR emitters
      is considered promising for fluorescent labels. 

PMID- 24433119
TI  - Ovarian hyperstimulation syndrome in systemic amyloidosis.
AB  - We report on the case of a young woman with a diagnosis of amyloidosis who
      developed severe portal and splenic venous thrombosis shortly after hormonal
      follicle stimulation therapy for oocyte preservation. The clinical implications
      are discussed.

PMID- 24433121
TI  - Risk factors of myasthenic crisis after thymectomy in 178 generalized myasthenia
      gravis patients in a five-year follow-up study.
AB  - PURPOSE: The aims of this study were to assess the clinical characteristics of
      patients with postoperative myasthenic crisis (PMC) and to identify the risk
      factors affecting the occurrence of PMC. METHOD: Extended thymectomy was
      performed on 178 patients with generalized MG with a mean onset age of 36.8
      years. The potentially risk factors were analyzed by binary logistic regression
      analysis. RESULT: During the over five-year follow-up, 44 patients (24.7%)
      experienced 58 episodes of PMC. The mean interval between surgery and the first
      episodes of PMC was 13.8 months, and for 81.8% of the patients it occurred within
      the first 2 years after thymectomy. Nine of 16 patients (56.3%) with a history of
      preoperative MC had recurrent crises. Respiratory tract infection was the most
      common precipitant of PMC. Univariate analysis showed that age at onset,
      preoperative MGFA class, preoperative MC, presence of bulbar symptoms, operation
      duration, amount of intraoperative blood loss, and the presence of thymoma were
      significantly associated with the occurrence of PMC. However, multivariate
      logistic regression analysis revealed that a history of preoperative MC (OR =
      2.845, p = 0.044), presence of bulbar symptoms (OR = 3.062, p = 0.027), and
      longer operation duration (OR = 1.026, p = 0.009) were the independent risk
      factors for PMC. CONCLUSION: The important risk factors for developing PMC in
      generalized MG patients include the presence of bulbar symptoms, history of
      preoperative MC, and longer operation duration. Optimization of the preoperative
      evaluation and proper perioperative care of MG patients may decrease the
      frequency of PMC.

PMID- 24433122
TI  - Cerebral white matter hyperintensities (WMH): an analysis of cerebrovascular risk
      factors in Lebanon.
AB  - BACKGROUND: Cerebral white matter hyperdensities (WMH) are frequently reported on
      brain magnetic resonance images (MRI) of elderly people; its significance is
      still under debate. METHODS: WMH subtypes may correlate with vascular risk
      factors, such as aging, hypertension (HTN) and diabetes mellitus (DM). The
      suggested hypothesis was to find if any of the periventricular WMH (PVWMH) or the
      deep WMH (DWMH) would be significantly more correlated with the above vascular
      risk factors. According to the Fazekas semiquantitative rating scale, we
      classified WMH into four subtypes: (1) absence of WMH, (2) presence of DWML, (3)
      presence of PVWMH, (4) presence of both DWML and PVWML. The study was performed
      on 257 Lebanese inpatients aged 40 years and above who underwent a brain MRI,
      regardless of their underlying pathology and who were admitted to an Internal
      Medicine Department in Beirut. The study patients were categorized into five
      subgroups by age intervals of 10 years. RESULTS: Mean age was 62; 54.1% were
      females; WMH were observed in 59.5% of study population; we found a linear
      correlation with WMH and aging with a clear shift for patients over age 60,
      reaching 84% in patients subgroup of 70-79-year-old and 94% patients subgroup
      over 80-year-old. PVWMH was found significantly more frequently and in linear
      correlation with aging and HTN. WMH were also found more frequently among the DM
      individuals. CONCLUSION: From this first ever retrospective Lebanese study, WMH
      was reported increasingly with aging in accordance with data from the literature;
      PVWMH was found significantly more correlated with aging and HTN than was DWMH
      alone.

PMID- 24433123
TI  - Ischemic preconditioning attenuates brain injury induced by ischemia/reperfusion
      during moderate hypothermia low-flow procedures.
AB  - OBJECTIVE: We determined the effects of ischemic preconditioning (IP) on
      apoptosis in a rat model of brain injury induced by cerebral ischemia/reperfusion
      following a moderate hypothermic low-flow (MHLF) procedure. METHODS: A total of
      180 rats were randomly divided into three groups. The surgery group was subjected
      to body temperature reduction and bilateral common carotid artery occlusion for
      120 min at 25 +/- 0.5 degrees C, followed by artery reopening and rewarming. The
      sham-surgery group underwent the same procedure, but common carotid arteries were
      not occluded. The ischemic preconditioning-treated surgery group was pretreated
      with four cycles of 2 min occlusion of bilateral common carotid arteries and 5
      min reperfusion, before 120 min of cerebral ischemia. Regional cerebral blood
      flow was measured continuously in 10 rats per group using laser Doppler
      flowmetry. We investigated brain cell apoptosis levels and mitochondrial
      apoptosis signaling pathway components at various time points following
      reperfusion. RESULTS: The ischemic preconditioning-treated surgery group
      displayed decreases in apoptotic cell numbers and apoptotic protein expression
      levels after the procedure at 6 h, 24 h, 72 h, and 7 d. Ischemic preconditioning
      inhibited cytochrome c release, caspase-3 activation, and mitochondrial apoptosis
      signaling pathway activation. CONCLUSION: The protective effects of ischemic
      preconditioning were associated with a reduction of DNA fragmentation, and
      inhibition of mitochondrial cytochrome c release and caspase-3 activation, which
      alleviated cerebral ischemia/reperfusion injury after moderate hypothermic low
      flow in rats. These findings highlight the potential of ischemic preconditioning
      as a neuroprotective therapy for surgery involving MHLF.

PMID- 24433126
TI  - Pairing vegetables with a liked food and visually appealing presentation:
      promising strategies for increasing vegetable consumption among preschoolers.
AB  - BACKGROUND: Vegetable consumption among preschool children is below recommended
      levels. New evidence-based approaches to increase preschoolers' vegetable intake,
      particularly in the child care setting, are needed. This study tests the
      effectiveness of two community-based randomized interventions to increase
      vegetable consumption and willingness to try vegetables: (1) the pairing of a
      vegetable with a familiar, well-liked food and (2) enhancing the visual appeal of
      a vegetable. METHODS: Fifty-seven preschoolers enrolled in a Child and Adult Care
      Food Program-participating child care center participated in the study; complete
      lunch and snack data were collected from 43 and 42 children, respectively. A
      within-subjects, randomized design was used, with order of condition
      counterbalanced. For lunch, steamed broccoli was served either on the side of or
      on top of cheese pizza. For a snack, raw cucumber was served either as
      semicircles with chive and an olive garnish or arranged in a visually appealing
      manner (in the shape of a caterpillar). Paired t-tests were used to determine
      differences in consumption of meal components, and McNemar's test was performed
      to compare willingness to taste. RESULTS: Neither visual appeal enhancement nor
      pairing with a liked food increased vegetable consumption. Pairing increased
      willingness to try the vegetable from 79% to 95% of children (p=0.07). Greater
      vegetable intake occurred at snack than at lunch. CONCLUSIONS: Further research
      should explore the strategy of pairing vegetables with liked foods. Greater
      consumption at snack underscores snack time as a critical opportunity for
      increasing preschool children's vegetable intake.

PMID- 24433129
TI  - Beta-thromboglobulin as a marker of perioperative myocardial infarction in
      patients undergoing coronary artery bypass grafting following aspirin
      discontinuation.
AB  - Perioperative myocardial infarction (PMI) following coronary artery bypass
      grafting (CABG) is associated with significant morbidity and mortality. The aim
      of this study was to assess platelet activation and oxidative stress in the
      setting of PMI in patients undergoing CABG. We studied 108 consecutive patients
      who stopped taking low-dose aspirin 7-10 days prior to elective isolated on- or
      off-pump CABG. beta-thromboglobulin (beta-TG), thromboxane B2 (TXB2) and 8-iso
      prostaglandin F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, were
      measured at the baseline and 5-7 days postoperatively. Aspirin (150 mg/d) was
      administered every morning since 12 hours after CABG. Mean baseline beta-TG was
      58.5 +/- 10.3 IU/ml, TXB2 was 143.6 +/- 28.5 ng/ml and 8-iso-PGF2alpha was 355.2
      +/- 40.7 pg/ml. Postoperatively, after administration of 4-6 doses of aspirin,
      beta-TG increased by 16.7% and 8-iso-PGF2alpha increased by 17.2% 5-7 days after
      surgery (p = 0.005 and p < 0.001, respectively). TXB2 decreased by 99.7% to 410.3
      +/- 52.1 pg/ml (p < 0.001). Nine patients (8.3%) developed PMI. Baseline beta-TG
      and TXB2, together with postoperative beta-TG and 8-iso-PGF2alpha were higher in
      PMI patients than in the remaining subjects (all, p < 0.05). Multivariate
      analysis showed that baseline beta-TG (OR: 1.28; 95% CI: 1.05-1.57, p = 0.015)
      was the only independent predictor of PMI. In conclusion, we demonstrated that
      increased platelet activation and thromboxane production, observed in patients
      not taking aspirin till the day of CABG, contribute to the occurrence of PMI in
      early postoperative period.

PMID- 24433132
TI  - An investigation of the implementation of NICE-recommended CBT interventions for
      people with schizophrenia.
AB  - BACKGROUND: The National Institute for Clinical Excellence (NICE) guidelines
      recommend that individual cognitive-behaviour therapy (CBT) is offered to all
      people with a diagnosis of schizophrenia. In addition, the guidelines recommend
      that family intervention (FI) should be offered to all families of people with
      schizophrenia who are in close contact with the service user. However,
      implementation into routine services is poor. AIMS: To survey mental health
      services to investigate how many people with a diagnosis of schizophrenia and
      their families are offered and receive CBT or FI. METHODS: A comprehensive audit
      of a random sample of 187 service users receiving care from one, large mental
      health care trust in North West England was conducted over a 12-month period.
      RESULTS: The audit recorded that only 13 (6.9%) of services users were offered
      and 10 (5.3%) received individual CBT, while 3 (1.6%) services users were offered
      and 2 (1.1%) received FIs within the 12-month audit period. CONCLUSIONS:
      Implementation of CBT and FI is poor, particularly for FI. Reasons for poor
      implementation and service implications are discussed.

PMID- 24433133
TI  - Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides
      containing an amino acid methyl ester and their analogues.
AB  - On the basis of the commercial insecticide chlorantraniliprole, a series of novel
      N-pyridylpyrazolecarboxamides containing an amino acid methyl ester and their
      analogues were designed and synthesized. Their chemical structures were
      established on the basis of corresponding (1) H NMR spectroscopy, (13)C NMR
      spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis.
      The insecticidal activities of the new compounds against oriental armyworm (
      Mythimna separata ) and diamondback moth ( Plutella xylostella ) were evaluated.
      The results of bioassays indicated that most of the compounds showed moderate to
      high activities at the tested concentration, of which the compounds 6 containing
      a methyl acrylate substructure had excellent larvicidal activity; for example, 6a
      displayed 100% larvicidal activity against P. xylostella at the concentration of
      0.005 mg/L, whereas the activities of both compounds 6g and 6h against M.
      separata were 100% at 2.5 mg/L. The calcium imaging technique experiment results
      showed that novel compound 6 could elevate the calcium concentration in the
      cytoplasm. Furthermore, this study also provided evidence that compound 6h
      activates inositol 1,4,5-trisphosphate (IP3) sensitive intracellular calcium
      release channels in the endoplasmic reticulum of Spodoptera exigua third-instar
      larva neurons. 

PMID- 24433134
TI  - Biomolecular mode of action of metformin in relation to its copper binding
      properties.
AB  - Metformin (Metf), the most commonly used type 2 diabetes drug, is known to affect
      the cellular housekeeping of copper. Recently, we discovered that the
      structurally closely related propanediimidamide (PDI) shows a cellular behavior
      different from that of Metf. Here we investigate the binding of these compounds
      to copper, to compare their binding strength. Furthermore, we take a closer look
      at the electronic properties of these compounds and their copper complexes such
      as molecular orbital interactions and electrostatic potential surfaces. Our
      results clearly show that the copper binding energies cannot alone be the cause
      of the biochemical differentiation between Metf and PDI. We conclude that other
      factors such as pKa values and hydrophilicity of the compounds play a crucial
      role in their cellular activity. Metf in contrast to PDI can occur as an anion in
      aqueous medium at moderate pH, forming much stronger complexes particularly with
      Cu(II) ions, suggesting that biguanides but not PDI may induce easy oxidation of
      Cu(I) ions extracted from proteins. The higher hydrophobicity and the lack of
      planarity of PDI may further differentiate it from biguanides in terms of their
      molecular recognition characteristics. These different properties could hold the
      key to metformin's mitochondrial activity because they suggest that the drug
      could act at least in part as a pro-oxidant of accessible protein-bound Cu(I)
      ions. 

PMID- 24433135
TI  - Graphene-coated surface plasmon resonance interfaces for studying the
      interactions between bacteria and surfaces.
AB  - A variety of physical and chemical parameters are of importance for adhesion of
      bacteria to surfaces. In the colonization of mammalian organisms for example,
      bacterial fimbriae and their adhesins not only seek particular glycan sequences
      exposed on diverse epithelial linings, they also enable the bacteria to overcome
      electrostatic repulsion exerted by their selected surfaces. In this work, we
      present a new technique based on simplified model systems for studying the
      adhesion strength of different Escherichia coli strains. For this purpose, gold
      based surface plasmon resonance (SPR) interfaces were coated with thin films of
      reduced graphene oxide (rGO) through electrophoretic deposition. The rGO matrix
      was post-modified with polyethyleneimine (PEI), poly(sodium 4-styrenesulfonate)
      (PSS), mannose, and lactose through pi-stacking and/or electrostatic interactions
      by simple immersion of the SPR interface into their respective aqueous solutions.
      The adhesion behaviors of one uropathogenic and two enterotoxigenic Escherichia
      coli clinical isolates, that each express structurally characterized fimbrial
      adhesins, were investigated. It was found that the UTI89 cystitis isolate that
      carries the mannose-binding FimH adhesin was most attracted to the PEI- and
      mannose-modified surfaces, whereas the att25 diarrhoeal strain with the N
      acetylglucosamine-specific F17a-G adhesin disintegrated the lactose-modified rGO.
      The highly virulent 107/86 strain interacted strongly with the PSS-modified
      graphene oxide, in agreement with the polybasic surroundings of the ABH blood
      group-binding site of the FedF adhesin, and showed a linear SPR response in a
      concentration range between 1 * 10(2) and 1 * 10(9) cfu/mL. 

PMID- 24433136
TI  - Unexpected self-assembly of chiral triangles from 90 degrees  chiral di-Pt(II)
      acceptors.
AB  - Two unexpected chiral organometallic triangles rather than squares from newly
      designed 90 degrees  chiral di-Pt(II) acceptors were obtained through
      coordination-driven self-assembly. Their structures were well characterized by
      multinuclear NMR ((1)H and (31)P) and variable-temperature NMR experiments, ESI
      TOF-MS, and elemental analysis. The PM6 semiempirical molecular simulation was
      employed for the interpretation of the formation and stability of such chiral
      triangles. 

PMID- 24433137
TI  - Ticagrelor as an alternative in clopidogrel-associated neutropenia.
AB  - Aspirin in combination with platelet P2Y12 receptor blocker has become the
      mainstay antiplatelet treatment strategy for the prevention of stent thrombosis.
      Ticlopidine was the first widely used P2Y12 receptor blockers, but clopidogrel
      has mostly replaced the use of ticlopidine due to its more favorable adverse
      event profile on bone marrow. However, when clopidogrel induced bone marrow
      toxicity occurs, little is known about the efficacy and safety of alternative
      treatments, and thus, in these cases, medical decisions may be very difficult. We
      report a case of clopidogrel-induced severe neutropenia in a patient treated with
      coronary stent and safety of alternative treatment with ticagrelor.

PMID- 24433138
TI  - Synthesis and characterization of glycoconjugated porphyrin triphenylamine
      hybrids for targeted two-photon photodynamic therapy.
AB  - In order to avoid side effects at the time of cancer eradication to the patients,
      the selectivity of treatments has become of strategic importance. In the case of
      photodynamic therapy (PDT), two-photon absorption combined with active targeting
      of tumors could allow both spatial and chemical selectivity. In this context, we
      present the synthesis, spectroscopic, and biological properties of a series of
      porphyrin-triphenylamine hybrids with excellent singlet oxygen production
      capacities and good two-photon absorption. 

PMID- 24433139
TI  - The additive impact of periodic limb movements during sleep on inflammation in
      patients with obstructive sleep apnea.
AB  - RATIONALE: Both periodic limb movements during sleep (PLMS) and obstructive sleep
      apnea (OSA) are major causes of sleep disorders and have been associated with
      systemic inflammation and cardiovascular events. However, it is uncertain whether
      in combination they promote a higher inflammatory response and greater risk of
      cardiovascular events than each condition alone. OBJECTIVES: To investigate
      whether the presence of PLMS is associated with increased inflammation in
      patients suspected of having OSA. METHODS: In 342 patients who underwent
      polysomnography to diagnose OSA, plasma C-reactive protein (CRP) and fibrinogen
      levels were measured. MEASUREMENTS AND MAIN RESULTS: OSA was found in 254
      patients, with 46 also having PLMS. Among the 88 patients who did not have OSA, 8
      had PLMS. Plasma CRP and fibrinogen levels in the group with both PLMS and OSA
      were higher than in patients with neither OSA nor PLMS and in patients with OSA
      only (CRP: 0.20 +/- 0.48 vs. 0.09 +/- 0.15 vs. 0.13 +/- 0.18 mg/dl, P = 0.03;
      fibrinogen: 298.2 +/- 76.1 vs. 269.0 +/- 57.1 vs. 270.0 +/- 52.6 mg/dl, P <
      0.01). Multivariate analysis showed that the presence of PLMS was associated with
      higher plasma CRP levels (beta = 0.1401, P < 0.01) and fibrinogen levels (beta =
      0.1359, P = 0.01) independently from other clinical variables such as body mass
      index and the severity of OSA. CONCLUSIONS: PLMS were positively associated with
      plasma CRP and fibrinogen levels in patients suspected of having OSA. Because
      plasma levels of these proteins have been established as predictive factors of
      future cardiovascular events, the presence of PLMS may be a useful clinical sign
      to identify patients with OSA at high risk of cardiovascular events.

PMID- 24433140
TI  - A study on the effects of fatigue driving and drunk driving on drivers' physical
      characteristics.
AB  - OBJECTIVE: The purpose of this study was to analyze the effects of fatigue
      driving and drunk driving on drivers' physical characteristics; to analyze the
      differences in drivers' physical characteristics affected by different kinds of
      fatigue; and to compare the differences in the effects of the 2 driving states,
      fatigue driving and drunk driving. METHODS: Twenty-five participants' physical
      characteristics were collected under 5 controlled situations: normal, tired
      driving, drowsy driving, drowsiness + tired driving, and drunk driving. In this
      article, fatigue driving refers to tiredness and drowsiness and includes 3
      situations: tired driving, drowsy driving, and drowsiness + tired driving. The
      drivers' physical characteristics were measured in terms of 9 parameters:
      systolic blood pressure (SBP), heart rate (HR), eyesight, dynamic visual acuity
      (DVA), time for dark adaption (TDA), reaction time to sound (RTS), reaction time
      to light (RTL), deviation of depth perception (DDP), and time deviation of speed
      anticipation (TDSA). They were analyzed using analysis of variance (ANOVA) with
      repeated measures. Binary logistical regression analysis was used to explain the
      relationship between drivers' physical characteristics and the two driving
      states. RESULTS: Most of the drivers' physical characteristic parameters were
      found to be significantly different under the influence of different situations.
      Four indicators are significantly affected by fatigue driving during deep fatigue
      (in decreasing order of influence): HR, RTL, SBP and RTS. HR and RTL are
      significant in the logistical regression model of the drowsiness + tired driving
      situation and normal situations. Six indicators of the drivers' physical
      characteristics are significantly affected by drunk driving (in decreasing order
      of influence): SBP, RTL, DDP, eyesight, RTS, and TDSA. SBP and DDP have a
      significant effect in the logistical regression model of the drunk driving
      situation and the normal situation. CONCLUSIONS: Both fatigue driving and drunk
      driving are found to impair drivers' physical characteristics. However, their
      impacts on the parameters SBP, HR, eyesight, and TDSA are different. A driver's
      physical characteristics will be impaired more seriously when he continues
      driving while drowsy, compared to driving under normal situation. These findings
      contribute to the current research on identifying drivers' driving state and
      quantifying the effects of fatigue driving and drunk driving on driving ability
      and driving behavior.

PMID- 24433141
TI  - New strategy to prepare hollow silica microspheres with tunable holes on the
      shell wall.
AB  - Hollow silica microspheres with holes of tunable numbers and sizes on the shell
      wall were prepared in this study. Clusters with positively charged polystyrene
      (PS) microspheres as the central spheres (CSs) and negatively charged PS spheres
      as the "halo" spheres (HSs) were formed via electrostatic interactions and
      utilized as a template. In the subsequent silica coating process, only CS was
      selectively coated; hence, after calcination, porous hollow silica microspheres
      were obtained. 

PMID- 24433143
TI  - Functionalization of homodiamantane: oxygen insertion reactions without
      rearrangement with dimethyldioxirane.
AB  - Homodiamantane bromination and nitroxylation are accompanied by contraction of
      the seven-membered ring to give the corresponding substituted 1-diamantylmethyl
      derivatives. In contrast, CH-bond hydroxylations with dimethyldioxirane retain
      the cage and give both apically and medially substituted homodiamantanes. The
      product ratios are in accord with the barriers for the oxygen insertion computed
      with density functional theory methods only if solvation is included through a
      polarizable continuum model. B3LYP-D3 and M06-2X computations with a 6-31G(d,p)
      basis set on the oligomeric van der Waals complexes predict the potential of
      homodiamantane derivatives for surface modifications with conformationally
      slightly flexible diamondoid homologues. 

PMID- 24433144
TI  - Mature VLDL triggers the biogenesis of a distinct vesicle from the trans-Golgi
      network for its export to the plasma membrane.
AB  - Post-Golgi trafficking of mature VLDL (very-low-density lipoprotein) is crucial
      in maintaining normal TAG (triacylglycerol) homoeostasis of hepatocytes; however,
      the mechanism that regulates the exit of mature VLDL from the TGN (trans-Golgi
      network) is not known. We developed an in vitro TGN-budding assay that allowed us
      to examine the formation of secretory vesicles from the TGN in primary rat
      hepatocytes. We isolated TAG-rich PG-VTVs (post-TGN VLDL transport vesicles)
      using a continuous sucrose density gradient. PG-VTVs were distributed in low
      density fractions, whereas protein transport vesicles were present in relatively
      higher-density fractions of the same sucrose gradient. EM revealed large intact
      PG-VTVs ranging 300-350 nm in size. The biogenesis of PG-VTVs from the TGN
      required cytosol, ATP, GTP hydrolysis and incubation at 37 degrees C. PG-VTVs
      concentrated the VLDL proteins: apolipoproteins apoB100, apoAIV, apoAI and apoE,
      but did not contain either albumin or transferrin. Proteinase K treatment did not
      degrade VLDL core proteins, suggesting that PG-VTVs were sealed. PG-VTVs were
      able to fuse with and deliver VLDL to the PM (plasma membrane) in a vectorial
      manner. We conclude that we have identified a new TGN-derived vesicle, the PG
      VTV, which specifically transports mature VLDL from the TGN to the PM.

PMID- 24433145
TI  - In situ transmission electron microscopy observation of electrochemical behavior
      of CoS(2) in lithium-ion battery.
AB  - Metal sulfides are a type of potential anode materials for lithium-ion batteries
      (LIBs). However, their electrochemical behaviors and mechanism during the charge
      and discharge process remain unclear. In the present paper, we use CoS2 as a
      model material to investigate their electrochemical process using in situ
      transmission electron microscopy (TEM). Two kinds of reaction behaviors are
      revealed. The pure CoS2 particles show a side-to-side conversion process, in
      which large and anisotropic size expansion (47.1%) occurs that results in the
      formation of cracks and fractures in CoS2 particles. In contrast, the CoS2
      particles anchored on reduced graphene oxide (rGO) sheets exhibit a core-shell
      conversion process involving small and homogeneous size expansion (28.6%) and few
      fractures, which attributes to the excellent Li(+) conductivity of rGO sheets and
      accounts for the improved cyclability. Single-crystalline CoS2 particle converts
      to Co nanocrystals of 1-2 nm embedded within Li2S matrix after the first
      lithiation. The subsequent electrochemical reaction is a reversible phase
      conversion between Co/Li2S and CoS2 nanocrystals. Our direct observations provide
      important mechanistic insight for developing high-performance conversion
      electrodes for LIBs. 

PMID- 24433146
TI  - Metalloproteomics: challenges and prospective for clinical research applications.
AB  - Metals are essential cofactors, utilized in many critical cellular processes. For
      example, zinc is important in insulin biosynthesis and may play a role in
      Alzheimer's disease, but much of how the zinc-mediated process remains unknown.
      Knowing which metal is in which protein at a given point in time would lead to
      new insights into how metals work in biological systems. New tools are being
      developed to investigate the biochemistry and cell biology of metals, with
      potential for biomedical applications. In this report, we consider the promise
      and limitations of metalloproteins detection techniques. We provide a brief
      overview of the techniques available and a discussion of the technical challenges
      to biomedical applications, with particular focus on what must be overcome for
      the potential of these approaches to be achieved. 

PMID- 24433147
TI  - Diagnosis and treatment of sleep apnoea in women with schizophrenia.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) is often overlooked in the context of
      schizophrenia because its hallmark, daytime sleepiness, is so easily attributable
      to antipsychotic drugs. This is a special problem for women. AIMS: To underscore
      the importance of diagnosing and treating OSA in women with schizophrenia.
      METHODS: A review of the recent literature (search terms: Obstructive Sleep
      Apnoea; Schizophrenia; Women (or Gender); Obesity; Antipsychotics; Continuous
      Positive Airway Pressure (CPAP)) as it applies to a composite case vignette taken
      from the files of a specialty clinic that treats women with psychosis. RESULTS:
      The rate of OSA in women who are both obese and postmenopausal is very similar to
      that of men. Family history, smoking, and the use of tobacco, alcohol and of
      antipsychotic medication increase the risk. Despite reluctance, patients with
      schizophrenia generally agree to undergo sleep studies. Compliance with CPAP is
      difficult, but can be aided by the physician and is, on the whole, relatively
      high in women. CPAP improves sleep parameters and may also improve
      cardiometabolic and cognitive indices, although this still needs to be more fully
      researched. CONCLUSION: Schizophrenia and untreated OSA are both associated with
      high mortality rates in women as well as men.

PMID- 24433149
TI  - The bone integration effects of platelet-rich fibrin by removal torque of
      titanium screw in rabbit tibia.
AB  - Platelet-rich fibrin (PRF) is nowadays often used in various fields, but no
      removal torque studies have yet been done to evaluate the effects of the platelet
      rich fibrin on the bone integration at the initial healing period. An
      experimental study have been performed in rabbits to evaluate whether the
      complete PRF clots can accelerate the bone integration of implants at the initial
      healing period after creating bone defects in tibias. The effect of the complete
      PRF clots on bone integration was studied in two rabbit groups, 4-week group
      (group A) and 6-week group (group B) after preparing bony defects. Artificial
      bony defects were prepared in the tibias of rabbits. The complete PRF clots was
      applied to the defects in the experimental group, whereas the defects were
      unfilled in the control group. Four weeks later, machined implants were installed
      into the rabbit tibias (group A). Six weeks after installation, the removal
      torque from nine rabbits was measured to examine the bone healing effect of PRF.
      In another rabbits (group B), 6 weeks after preparing bony defects, installation
      was performed, and another 6 weeks after installation, the removal torque from
      nine rabbits was measured. The authors found a positive significant effect of the
      complete PRF clots on bone integration (higher bone density) in group A installed
      at 4 weeks after preparing bony defects (p = 0.008; t-test), but not in group B
      installed at 6 weeks after preparing bony defects (p = 0.677).

PMID- 24433150
TI  - Using transcriptomic tools to evaluate biological effects across effluent
      gradients at a diverse set of study sites in Minnesota, USA.
AB  - The aim of this study was to explore the utility of "omics" approaches in
      monitoring aquatic environments where complex, often unknown stressors make
      chemical-specific risk assessment untenable. We examined changes in the fathead
      minnow (Pimephales promelas) ovarian transcriptome following 4-day exposures
      conducted at three sites in Minnesota (MN, USA). Within each site, fish were
      exposed to water from three locations along a spatial gradient relative to a
      wastewater treatment plant (WWTP) discharge. After exposure, site-specific
      impacts on gene expression in ovaries were assessed. Using an intragradient point
      of comparison, biological responses specifically associated with the WWTP
      effluent were identified using functional enrichment analyses. Fish exposed to
      water from locations downstream of the effluent discharges exhibited many
      transcriptomic responses in common with those exposed to the effluent, indicating
      that effects of the discharge do not fully dissipate downstream. Functional
      analyses showed a range of biological pathways impacted through effluent exposure
      at all three sites. Several of those impacted pathways at each site could be
      linked to potential adverse reproductive outcomes associated with the
      hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows, specifically
      signaling pathways associated with oocyte meiosis, TGF-beta signaling,
      gonadotropin-releasing hormone (GnRH) and epidermal growth factor receptor family
      (ErbB), and gene sets associated with cyclin B-1 and metalloproteinase. The
      utility of this approach comes from the ability to identify biological responses
      to pollutant exposure, particularly those that can be tied to adverse outcomes at
      the population level and those that identify molecular targets for future
      studies. 

PMID- 24433151
TI  - Structural determination of a nivalenol glucoside and development of an
      analytical method for the simultaneous determination of nivalenol and
      deoxynivalenol, and their glucosides, in wheat.
AB  - Trichothecene mycotoxins such as nivalenol and deoxynivalenol frequently
      contaminate foodstuffs. Recently, several trichothecene glucosides have been
      found in trichothecene-contaminated foods, and information about their chemistry,
      toxicity, and occurrence is required. In this study, a glucoside of nivalenol was
      isolated from nivalenol-contaminated wheat and was identified as nivalenol-3-O
      beta-D-glucopyranoside. Analytical methods using a multifunctional column or an
      immunoaffinity column have been developed for the simultaneous determination of
      nivalenol, nivalenol-3-O-beta-D-glucopyranoside, deoxynivalenol, and
      deoxynivalenol-3-O-beta-D-glucopyranoside in wheat. The methods were validated in
      a single laboratory, and recovery from wheat samples spiked at four levels ranged
      between 86.4 and 103.5% for the immunoaffinity column cleanup. These mycotoxins
      in contaminated wheat samples were quantitated by the validated method. Nivalenol
      3-O-beta-D-glucopyranoside was detected in the nivalenol-contaminated wheat, and
      the percentage of nivalenol-3-O-beta-D-glucopyranoside to nivalenol ranged from
      12 to 27%. This result indicates that the analytical method developed in this
      study is useful for obtaining data concerning the state and level of food
      contamination by nivalenol, deoxynivalenol, and their glucosides.

PMID- 24433152
TI  - Stability of VerifyNow P2Y12 assay results with citrate anticoagulation as
      compared to hirudin anticoagulation over 20-min period.

PMID- 24433153
TI  - Characterization of aerobically fit individuals with cardiovascular disease.
AB  - With an ageing population there is an increased prevalence of individuals living
      with cardiovascular disease (CVD). Characteristics of older aerobically fit
      individuals with previously diagnosed CVD have not been studied. Therefore, our
      knowledge is limited as to how, or if, aerobically fit individuals with CVD
      attempt to adapt their physical activity and the intensity of their training
      programmes. The objective of this paper is to characterise the physical activity
      habits and behaviours of older aerobically fit individuals with CVD. We
      identified 28 aerobically fit patients with CVD from those who completed a
      minimum of 15 and 12 min of the Bruce treadmill protocol for men and women,
      respectively. Consenting participants responded to questionnaires regarding
      physical activity levels, competitive event participation and self-monitoring
      since diagnosis of heart disease. Average age and treadmill time of participants
      were 56 and 49 years and 15.6 and 13.0 min for males and females, respectively.
      Data were obtained regarding recent medical history (medical diagnoses,
      surgeries/procedures). Despite the majority of individuals participating in the
      same or more activity since their diagnosis, 25% indicated that their condition
      limited their activity and 39% reported having symptoms during activity. Nearly
      all participants (93%) indicated that they monitored their heart rate during
      exercise. However, only 14% of participants stated that their physician advised
      them on how to exercise safely. It is necessary for physicians and cardiac
      rehabilitation programmes to be involved in safe and effective exercise
      programming to allow individuals to return to sport after CVD.

PMID- 24433154
TI  - Leveraging the micellar effect: gold-catalyzed dehydrative cyclizations in water
      at room temperature.
AB  - The first examples of gold-catalyzed cyclizations of diols and triols to the
      corresponding hetero- or spirocycles in an aqueous medium are presented. These
      reactions take place within nanomicelles, where the hydrophobic effect is
      operating, thereby driving the dehydrations, notwithstanding the surrounding
      water. By the addition of simple salts such as sodium chloride, reaction times
      and catalyst loadings can be significantly decreased. 

PMID- 24433158
TI  - Development, calibration, and validation of a head-neck complex of THOR mod kit
      finite element model.
AB  - INTRODUCTION/OBJECTIVE: In an effort to continually improve upon the design of
      the test device for human occupant restraint (THOR) dummy, a series of
      modifications have recently been applied. The first objective of this study was
      to update the THOR head-neck finite element (FE) model to the specifications of
      the latest dummy modifications. The second objective was to develop and apply a
      new optimization-based methodology to calibrate the FE head-neck model based on
      experimental test data. The calibrated head-neck model was validated against both
      frontal and lateral impact test data. Finally, the sensitivities of the model, in
      terms of head and neck injury criteria, to pretest positioning conditions were
      evaluated in a frontal crash test simulation. METHODS: The updated parts of the
      head-neck THOR FE model were remeshed from CAD geometries of the modified parts.
      In addition, further model modifications were made to improve the effectiveness
      of the model (e.g., model stability). A novel calibration methodology, which
      incorporates the CORA (CORelation and Analysis) rating system with an
      optimization algorithm implemented in Isight software, was developed to improve
      both kinematic and kinetic responses of the model in various THOR dummy
      certification and biomechanical response tests. A parametric study was performed
      to evaluate head and neck injury criteria values in the calibrated head-neck
      model during a 40 km/h frontal crash test with respect to variation in the THOR
      model upper body and belt pretest position. RESULTS: Material parameter
      optimization was shown to greatly improve the updated model response by
      increasing the average rating score from 0.794 +/- 0.073 to 0.964 +/- 0.019. The
      calibrated neck showed the biggest improvement in the pendulum flexion simulation
      from 0.681 in the original model up to 0.96 in the calibrated model. The fully
      calibrated model proved to be effective at predicting dummy response in frontal
      and lateral loading conditions during the validation phase (0.942 average score).
      Upper body position was shown to have a greater effect on head-neck response than
      belt position. The pretest positioning variation resulted in a 10 percent maximum
      change in HIC36 values and 14 percent maximum change in NIJ values. CONCLUSION:
      The optimization-based calibration methodology was effective as it markedly
      improved model performance. The calibrated head-neck model demonstrated
      application in a crash safety analysis, showing slight head-neck injury
      sensitivity to pretest positioning in a frontal crash impact scenario.

PMID- 24433159
TI  - Arynes double bond insertion/nucleophilic addition with vinylogous amides and
      carbodiimides.
AB  - Arynes are shown to insert into some C?X double bonds, leading to benzannulated
      four-membered rings. The strain of these rings allow for a ready, spontaneous
      opening to afford o-quinomethide analogues. Subsequent nucleophilic addition re
      aromatizes the intermediates to achieve ortho-difunctionalization of arynes. In
      this report, we describe the aryne insertion into the C?C double bonds of
      vinylogous amides and the C?N double bonds of carbodiimides. The correlation and
      comparison with aryne single bond insertion chemistry will be discussed.
      Computational studies for the ring-opening step, as well as the nature of the o
      quinomethide intermediates, will also be discussed.

PMID- 24433163
TI  - Pseudotumor cerebri pathophysiology.
AB  - Pseudotumor cerebri syndrome (PTCS) is an uncommon disorder of raised
      intracranial pressure of unknown etiology. The signs and symptoms have been well
      described but the pathogenesis remains a mystery. Most of the evidence suggests
      increased resistance to cerebrospinal fluid outflow as being pivotal to the
      disorder. Any comprehensive theory on causation will have to explain the
      preponderance of obese women of childbearing age with primary PTCS and lack of
      ventriculomegaly in the disorder. It is possible that female sex hormones, along
      with endocrinologically active adipose tissue, directly result in the syndrome,
      in those genetically predisposed. Aldosterone has been proposed also as important
      in the development of PTCS. Vitamin A, in the form of retinoic acid, may also
      play a pivotal role, and is influenced by both estrogen and adipose tissue. This
      article reviews proposed mechanisms of PTCS. 

PMID- 24433162
TI  - Frataxin-bypassing Isu1: characterization of the bypass activity in cells and
      mitochondria.
AB  - Frataxin is a conserved mitochondrial protein, and deficiency underlies the
      neurodegenerative disease Friedreich's ataxia. Frataxin interacts with the core
      machinery for Fe-S cluster assembly in mitochondria. Recently we reported that in
      frataxin-deleted yeast strains, a spontaneously occurring mutation in one of two
      genes encoding redundant Isu scaffold proteins, bypassed the mutant phenotypes.
      In the present study we created strains expressing a single scaffold protein,
      either Isu1 or the bypass mutant M107I Isu1. Our results show that in the
      frataxin-deletion strain expressing the bypass mutant Isu1, cell growth, Fe-S
      cluster protein activities, haem proteins and iron homoeostasis were restored to
      normal or close to normal. The bypass effects were not mediated by changes in
      Isu1 expression level. The persulfide-forming activity of the cysteine
      desulfurase was diminished in the frataxin deletion (?yfh1 ISU1) and was improved
      by expression of the bypass Isu1 (?yfh1 M107I ISU1). The addition of purified
      bypass M107I Isu1 protein to a ?yfh1 lysate conferred similar enhancement of
      cysteine desulfurase as did frataxin, suggesting that this effect contributed to
      the bypass mechanism. Fe-S cluster-forming activity in isolated mitochondria was
      stimulated by the bypass Isu1, albeit at a lower rate. The rescuing effects of
      the bypass Isu1 point to ways that the core defects in Friedreich's ataxia
      mitochondria can be restored.

PMID- 24433164
TI  - Aberrant histone methylation in the patients with immune thrombocytopenia.
AB  - Abstract The aim of the present study was to investigate alterations in histone
      methylation in patients with primary immune thrombocytopenia (ITP). Global
      histone H3K4/H3K9 methylation in CD4+ T cells from 35 ITP patients and 15 healthy
      controls were measured using the EpiQuik(TM) global histone H3K4/H3K9 methylation
      assay kits. The mRNA expression of SUV39H1, SUV39H2 and EZH2 were detected by
      real-time quantitative polymerase chain reaction (RT-PCR). The results showed
      that global histone H3K9 hypomethylation in CD4+ T cells of active ITP, compared
      with ITP in remission and controls, while the global histone H3K4 methylation
      were not significantly different between ITP patients and healthy controls. The
      expression of EZH2 and SUV39H2 were significantly down-regulated in active ITP
      patients, when compared with ITP in remission and controls. There were not
      different between ITP patients and controls in the expression SUV39H1. In
      conclusion, the aberrant histone methylation was involved in the pathogenesis of
      ITP. 

PMID- 24433165
TI  - Reading self-help literature in Russia: governmentality, psychology and
      subjectivity.
AB  - Self-help has become a booming business over the past decades and an increasingly
      visible part of popular media culture worldwide. The paper analyzes the arrival
      and effects of this cultural technology in post-Soviet Russia after more than
      seventy years of socialism. It examines how Russians are engaging with popular
      psychology self-help as a technology of the self and how they are making it
      meaningful in their lives. Drawing on a set of one-to-one and focus group
      interviews conducted with self-help readers, it examines how these individuals
      negotiate the new ethics and the normative models of personhood put forward by
      the self-help genre. It argues that popular psychology has offered a new language
      for making sense of the self and the social world, and highlights how the readers
      critically engage with the normalizing power of popular psychology by drawing on
      a number of local historically sedimented discourses. 

PMID- 24433166
TI  - Survival of Mycobacterium avium subsp. paratuberculosis in ultra-filtered white
      cheese.
AB  - Mycobacterium avium subsp. paratuberculosis (Map) is considered as a potential
      public health threat due to its possible association with Crohn's disease in
      humans. This study aimed to investigate the survival of Map in ultra-filtered
      white (UFW) cheese, with special reference to the effect of initial inoculum
      level, addition of starter culture and salt concentration. Behaviour of Map was
      monitored during the storage of UFW cheese using F57-quantitative real-time PCR
      and culture assay. According to the results, higher inoculum level prolongs Map
      persistence in UFW cheese. Furthermore, the addition of starter culture was found
      as the main restrictive parameter affecting the survival of Map in UFW cheese.
      Meanwhile, salt concentration did not accelerate Map inactivation. It was
      concluded that UFW cheese has potential to support the survival of Map.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study was conducted to investigate the
      factors that influence the survival of Mycobacterium avium subsp.
      paratuberculosis (Map) during the storage period of ultra-filtered white (UFW)
      cheese which represents a step forward to meet a critical industry need. Results
      revealed that the addition of starter culture could restrict the persistence of
      Map, while Map survival was not affected by higher salt concentration. In
      addition, persistence of Map was found dose-dependent. It was concluded that in
      UFW cheese, Map could survive the 60 days of storage period.

PMID- 24433167
TI  - Treatment preferences among men attending outpatient psychiatric services.
AB  - BACKGROUND: The assumption that men dislike psychotherapy has been espoused by
      clinicians, health care administrators, and those in the popular media. Whether
      this assumption holds true among help-seeking men has not been tested. AIMS:
      Treatment preferences of men attending outpatient psychiatric clinics were
      investigated to assess their willingness to engage in psychotherapy. METHODS: In
      three different studies (total N = 407; 170 men), male and female outpatients
      completed various self-report measures that assessed their treatment preferences,
      as well as psychiatric symptoms. RESULTS: Across all three studies, men indicated
      a preference for psychotherapy over medication or no treatment/wait and see; a
      preference pattern that did not differ significantly from that of women. The only
      between-sex difference to emerge regarding preferences was in study 2; a greater
      proportion of men preferred individual therapy over group therapy compared to
      women. There were no between-sex differences with regard to symptoms.
      CONCLUSIONS: Contrary to assumptions that portray men, generally, as unwilling or
      uninterested to engage in psychotherapy, men that have sought mental health
      services appear to prefer psychotherapy as their intervention of choice to
      address their mental health problems.

PMID- 24433168
TI  - Emil du Bois-Reymond on "The Seat of the Soul".
AB  - The German pioneer of electrophysiology, Emil du Bois-Reymond (1818-1896), is
      generally assumed to have remained silent on the subject of the brain. However,
      the archive of his papers in Berlin contains manuscript notes to a lecture on
      "The Seat of the Soul" that he delivered to popular audiences in 1884 and 1885.
      These notes demonstrate that cerebral localization and brain function in general
      had been concerns of his for quite some time, and that he did not shy away from
      these subjects. 

PMID- 24433169
TI  - Mutants of phospholipase A (pPLA-I) have a red light and auxin phenotype.
AB  - pPLA-I is the evolutionarily oldest patatin-related phospholipase A (pPLA) in
      plants, which have previously been implicated to function in auxin and defence
      signalling. Molecular and physiological analysis of two allelic null mutants for
      pPLA-I [ppla-I-1 in Wassilewskija (Ws) and ppla-I-3 in Columbia (Col) ] revealed
      pPLA-I functions in auxin and light signalling. The enzyme is localized in the
      cytosol and to membranes. After auxin application expression of early auxin
      induced genes is significantly slower compared with wild type and both alleles
      show a slower gravitropic response of hypocotyls, indicating compromised auxin
      signalling. Additionally, phytochrome-modulated responses like abrogation of
      gravitropism, enhancement of phototropism and growth in far red-enriched light
      are decreased in both alleles. While early flowering, root coils and delayed
      phototropism are only observed in the Ws mutant devoid of phyD, the light-related
      phenotypes observed in both alleles point to an involvement of pPLA-I in
      phytochrome signalling. 

PMID- 24433170
TI  - Isothiourea-mediated one-pot synthesis of trifluoromethyl substituted 2-pyrones.
AB  - A one-pot isothiourea-mediated Michael addition/lactonization/thiol elimination
      cascade sequence for the formation of 4,6-disubstituted and 3,4,6-trisubstituted
      2-pyrones from (phenylthio)acetic acids and alpha,beta-unsaturated
      trifluoromethyl ketones is described. The synthesis of a COX-2 inhibitor and the
      wide-ranging derivatization of the 2-pyrone moiety to trifluoromethyl substituted
      aromatics and heteroaromatics is also disclosed. 

PMID- 24433171
TI  - Determination of hepatotoxic indospicine in Australian camel meat by ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - Indospicine is a hepatotoxic amino acid found in Indigofera plant spp. and is
      unusual in that it is not incorporated into protein but accumulates as the free
      amino acid in the tissues (including muscle) of animals consuming these plants.
      Dogs are particularly sensitive to indospicine, and secondary poisoning of dogs
      has occurred from the ingestion of indospicine-contaminated horse meat and more
      recently camel meat. In central Australia, feral camels are known to consume
      native Indigofera species, but the prevalence of indospicine residues in their
      tissues has not previously been investigated. In this study, a method was
      developed and validated with the use of ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) to determine the level of indospicine in
      camel meat samples using isotopically labeled indospicine as an internal
      standard. UPLC-MS/MS analysis showed that the method is reproducible, with high
      recovery efficiency and a quantitation limit of 0.1 mg/kg. Camel meat samples
      from the Simpson Desert were largely contaminated (~50%) by indospicine with
      levels up to 3.73 mg/kg (fresh weight) determined. However, the majority of
      samples (95%) contained less than 1 mg/kg indospicine. 

PMID- 24433174
TI  - Mean platelet volume and red cell distribution width in autoimmune gastritis:
      confounding factors should be considered.

PMID- 24433175
TI  - The ancient Britons: groundwater fauna survived extreme climate change over tens
      of millions of years across NW Europe.
AB  - Global climate changes during the Cenozoic (65.5-0 Ma) caused major biological
      range shifts and extinctions. In northern Europe, for example, a pattern of few
      endemics and the dominance of wide-ranging species is thought to have been
      determined by the Pleistocene (2.59-0.01 Ma) glaciations. This study, in
      contrast, reveals an ancient subsurface fauna endemic to Britain and Ireland.
      Using a Bayesian phylogenetic approach, we found that two species of stygobitic
      invertebrates (genus Niphargus) have not only survived the entire Pleistocene in
      refugia but have persisted for at least 19.5 million years. Other Niphargus
      species form distinct cryptic taxa that diverged from their nearest continental
      relative between 5.6 and 1.0 Ma. The study also reveals an unusual
      biogeographical pattern in the Niphargus genus. It originated in north-west
      Europe approximately 87 Ma and underwent a gradual range expansion. Phylogenetic
      diversity and species age are highest in north-west Europe, suggesting resilience
      to extreme climate change and strongly contrasting the patterns seen in surface
      fauna. However, species diversity is highest in south-east Europe, indicating
      that once the genus spread to these areas (approximately 25 Ma), geomorphological
      and climatic conditions enabled much higher diversification. Our study highlights
      that groundwater ecosystems provide an important contribution to biodiversity and
      offers insight into the interactions between biological and climatic processes. 

PMID- 24433176
TI  - Alopecia in a patient with Vogt-Koyanagi-Harada disease.

PMID- 24433177
TI  - Epidermal growth factor receptor and the sebaceous gland.
AB  - Side effects of EGFR inhibition do not include primary sebaceous gland changes.
      Dahlhoff et al. evaluated EGFR actions on the sebaceous glands in mutant mice
      with constitutively activated EGFR expression. Enlarged, hyperproliferative
      sebaceous glands and increased sebum levels were detected, and c-myc levels were
      increased. These data indicate that EGFR-induced sebocyte mechanisms are probably
      species-specific. The detected SCD deregulation is compatible with previous
      reports, whereas SCD is a marker of sebaceous differentiation, and its expression
      is essential for lipogenesis. As SCD expression is upregulated by TLR2
      activation, there is a link between SCD overexpression and sebaceous
      differentiation/lipogenesis with inflammation. 

PMID- 24433178
TI  - Commentary on: Hairless and the polyamine putrescine form a negative regulatory
      loop in the epidermis.
AB  - Polyamines are cationic amines essential for cellular proliferation. Recently,
      their role in hair follicle (HF) growth has started to be explored, but their
      exact function is still obscure. In the October issue of Experimental
      Dermatology, Luke et al. follow the observation that putrescine overproducing
      mice and hairless (HR) mutant mice show a similar clinical phenotype of hair loss
      and dermal cyst formation. They show that HR and putrescine form a negative
      regulatory feedback mechanism, which might regulate hair cycling and therefore
      control hair growth. This study clearly demonstrates that a strong connection
      exists between HR and polyamines although there are probably additional molecular
      pathways involved in the polyamine regulation of hair growth which remain to be
      discovered. 

PMID- 24433179
TI  - Autoreactive T cells in the immune pathogenesis of pemphigus vulgaris.
AB  - Pemphigus vulgaris is a life-threatening autoimmune blistering disease caused by
      anti-desmoglein IgG autoantibodies that finally lead to acantholysis presenting
      clinically as progressive blistering. Whilst the production of pathogenic
      antibodies is key to the development of pemphigus vulgaris, many immunological
      steps are required prior to autoantibody induction. We review advances in the
      understanding of these immunologic processes with a focus on human leucocyte
      antigen polymorphisms and antigen recognition, epitope spreading, central and
      peripheral tolerance, T helper differentiation, induction of pro- and anti
      inflammatory cytokines and T-cell regulation of B cells. Targeting autoaggressive
      T cells as regulators and stimulators of B-cell antibody production should allow
      for more specific therapeutic immune interventions, avoiding the global
      immunosuppression seen with many commonly used immunosuppressants in pemphigus
      vulgaris. 

PMID- 24433180
TI  - Leukotrienes orchestrating allergic skin inflammation.
AB  - Leukotrienes constitute a group of lipid mediators, which may be subdivided into
      two groups, with leukotriene B4 on the one hand and cysteinyl leukotrienes on the
      other. Although leukotrienes are abundantly expressed in skin affected by diverse
      chronic inflammatory diseases, including atopic dermatitis, psoriasis, pemphigus
      vulgaris and bullous pemphigoid, their pathological roles in these diseases have
      remained elusive. Recent data now reveal that both leukotriene B4 and cysteinyl
      leukotrienes are indispensable in the pathogenesis of atopic dermatitis, with
      leukotriene B4 initiating the recruitment of inflammatory cells, particularly
      neutrophils and TH 2 cells into the skin, and cysteinyl leukotrienes later
      inducing characteristic structural alterations of chronically affected skin,
      specifically skin fibrosis and keratinocyte proliferation. Thus, these results
      reveal a sequential cooperation of LTB4 and cysteinyl leukotrienes to initiate
      and perpetuate allergic skin inflammation. These new insights highlight
      leukotrienes as promising therapeutic targets in allergic skin inflammation and
      should encourage more research into the role of leukotrienes in other
      inflammatory skin diseases. 

PMID- 24433181
TI  - Endothelial cells are highly heterogeneous at the level of cytokine-induced
      insulin resistance.
AB  - The endothelial wall plays a crucial role in various diseases as it serves as the
      barrier between circulatory system and organ tissue. Inflammation-driven insulin
      resistance and subsequent endothelial dysfunction represent a pathomechanism in
      cardiovascular diseases such as atherosclerosis and myocardial infarction. It was
      recently suggested that insulin resistance also contributes to the pathogenesis
      of psoriasis, a chronic inflammatory disease of the skin. However, it is not
      clear whether similar mechanisms at the endothelium contribute to the disease. In
      this study, we ask which endothelial cells are most suitable to address this
      question. We investigated the insulin response of four cell types (primary cells
      and cell lines) representing different vascular beds (micro- and macrovascular
      cells) in the presence of different pro-inflammatory cytokines. All four cell
      types used responded well to insulin; however, the ability to become resistant to
      insulin due to an inflammatory stimulus by cytokines involved in psoriasis (e.g.
      IL-1beta, IL-12, IL-17, IL-23 and TNF-alpha) was very heterogeneous and could not
      be attributed to the differential expression of the cognate cytokine receptors.
      We conclude that this disparity is due to the different origins and properties of
      the endothelial cells used. Thus, endothelial cells should be carefully selected
      for the purpose of the respective study, particularly when it comes to analysing
      the pathogenesis of a disease and the search of new molecular targets for
      innovative therapies. 

PMID- 24433182
TI  - Serum levels of leptin receptor in patients with malignant melanoma as a new
      tumor marker.
AB  - Leptin is known to be abnormally expressed in a variety of cancers, and leptin
      receptors have been reported to be expressed on human melanoma cells. In this
      study, we evaluated the possibility that the serum levels of leptin receptor
      could be a tumor marker of malignant melanoma (MM). Serum samples were obtained
      from 71 patients with MM, and the serum levels of leptin receptor were measured
      by double-determinant ELISA. Interestingly, serum levels of leptin receptor
      decreased gradually with the stages of MM, being highest at in situ and lowest at
      stage IV. There was also a trend of reverse correlation between tumor thickness
      and serum levels of leptin receptor. To our knowledge, this is the first report
      investigating the serum levels of leptin receptor in MM, and serum leptin
      receptor levels may be used as a useful tumor marker of MM. 

PMID- 24433183
TI  - The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin-43
      dephosphorlyation during epidermal barrier acquisition.
AB  - Epidermal barrier acquisition during late mammalian development is a prerequisite
      for terrestrial existence. Over a 24-h period, the epidermis goes from being a
      barrier-deficient, dye permeable epithelium to a barrier-competent epithelium. We
      have previously shown that Akt signalling is necessary for barrier acquisition in
      the mouse and that the protein phosphatase 2A regulatory subunit Ppp2r2a causes
      barrier acquisition by dephosphorylation of cJun. Here, we demonstrate that there
      is transient interaction between the gap junction protein Connexin 43 (Cx43) and
      Zonula occludins-1 (Zo-1) during epidermal barrier acquisition. Ppp2r2a knockdown
      prevented plasma membrane co-localisation and interaction between the two
      proteins. Ppp2r2a knockdown also increased phosphorylation at Serine 368 of
      Connexin 43. Cx43 phosphorlyation at Serine368 occurred just prior to the
      interaction between Connexin 43 and Zo-1. We therefore propose a model in which
      Ppp2r2a is required both for the initial interaction between Zo-1 and Cx43 and
      the consequent dephosphorylation of Connexin 43, preventing interaction of Zo-1
      and allowing Zo-1 to initiate tight junction formation and barrier acquisition. 

PMID- 24433184
TI  - Lecithin retinol acyltransferase as a potential prognostic marker for malignant
      melanoma.
AB  - Metabolism inside cells differs between cancer and normal cells. Because
      disturbance of vitamin A metabolism might be important, we investigated
      expression of the enzymes lecithin retinol acyltransferase (LRAT) and RPE65 by
      immunohistochemistry in melanoma metastases and melanocytic nevi.
      Semiquantitative evaluation of this expression revealed downregulated expression
      of RPE65 in malignant melanoma compared with benign melanocytic nevi (P < 0.001).
      In contrast, expression of LRAT was not significantly different (P = 0.339). High
      LRAT expression in melanoma metastases was inversely correlated with patient
      survival; Kaplan-Meier analysis revealed earlier melanoma-related death (P =
      0.003). Expression of LRAT might, therefore, be a prognostic marker of the
      clinical course of melanoma. 

PMID- 24433185
TI  - Insufficient expression of the melanocortin-1 receptor by human dermal
      fibroblasts contributes to excess collagen synthesis in keloid scars.
AB  - Activation of the alpha-melanocyte-stimulating hormone (alphaMSH)/melanocortin-1
      receptor (MC1R) signalling pathway exerts antagonistic actions on cutaneous
      inflammatory and fibrogenic responses in addition to promoting pigment
      production. Herein, the expression of MC1R by keloid-derived fibroblasts and
      keloid scar tissue was investigated using a range of techniques. MC1R mRNA
      expression levels in five different keloid fibroblast cell lines were
      significantly reduced to less than half compared with five normal fibroblast cell
      lines (P < 0.05). Immunohistological analysis of tissue samples indicated that
      MCR1 immunoreactivity in both epidermal and dermal compartments of five keloid
      tissue samples was dramatically decreased compared with normal skin (P < 0.05).
      Insufficient expression of MC1R on human dermal fibroblasts might abolish the
      alphaMSH-mediated suppression of collagen production and myofibroblast
      transformation elicited by the profibrotic cytokine-transforming growth factor
      beta1. Restoration of reduced MC1R by dermal fibroblasts may lead to novel scar
      reducing therapeutic approaches for treating this refractory fibrotic disease. 

PMID- 24433187
TI  - Predictors of antiplatelet response to prasugrel during maintenance treatment.
AB  - Insufficient P2Y12 receptor inhibition is associated with a higher risk of
      thrombotic events after percutaneous coronary intervention (PCI). The third
      generation thienopyridine prasugrel achieves stronger platelet inhibition as
      compared to its predecessor clopidogrel. Little is known about predictors of
      prasugrel drug responsiveness. The aim of this study was to explore predictors of
      prasugrel responsiveness in patients with a recent PCI on prasugrel maintenance
      dose (MD) treatment. In a registry of PCI-treated patients (n = 163, recruited
      between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced
      platelet aggregation (PA) was assessed on a Multiplate analyzer. The mean
      (interquartile range (IQR)) ADP-induced PA on prasugrel MD treatment was 206 (138
      331) AU * min. Obese (defined by a body mass index (BMI) >= 30) patients (n = 42)
      (303 [192-467] vs. 187 [117-305] AU * min, p = 0.0001), patients (n = 70) with a
      history of clopidogrel low responsiveness (278 [161-409] vs. 192 [126-282] AU *
      min, p = 0.002) and patients (n = 18) on a low (5 mg) prasugrel MD (483 [252-798]
      vs. 198 [133-313] AU * min; p = 0.0001) showed higher PA values on prasugrel MD
      as compared to the remaining patients. In a multivariable linear regression
      model, the latter three variables were independently associated with higher PA
      values on prasugrel MD treatment. In summary response variability is observed in
      patients on prasugrel MD treatment. Obesity, a history of clopidogrel low
      responsiveness and a reduced prasugrel MD of 5 mg are independent predictors of
      an attenuated response to prasugrel treatment. Further studies are needed to
      explore clinical implications of this observation.

PMID- 24433188
TI  - Cellular redox homeostasis in endothelial cells treated with nonmodified and
      Fenton-modified nanodiamond powders.
AB  - Diamond nanoparticles find numerous applications in pharmacy, medicine,
      cosmetics, and biotechnology. However, possible adverse cellular effects of
      diamond nanoparticle cells have been reported, which may limit their use. The aim
      of this study was to compare the effect of nonmodified diamond nanoparticles (D)
      and diamond nanoparticles modified by the Fenton reaction (D+OH) on human
      umbilical cord endothelial cells (HUVEC-ST). We found that both D and D+OH show
      time- and concentration-dependent cytotoxicity, inducing apoptosis and necrosis
      of HUVEC-ST. Interaction with D and D+OH also induced changes in the production
      of reactive oxygen and nitrogen species and changes in the level of glutathione
      and activities of antioxidant enzymes in the cells. These data demonstrate that
      diamond nanoparticles may induce oxidative stress in human endothelial cells,
      which contributes to their cytotoxic effects seen at higher concentrations of D
      and D+OH. 

PMID- 24433193
TI  - Value motivations predict burnout and intentions to leave among mental health
      professionals.
AB  - BACKGROUND: Values guide and potentially motivate people in their lives. Aligning
      personal values with organisational values has the potential to improve job
      satisfaction, reduce burnout and lower Intentions To Leave (ITL). AIMS: To
      determine whether changes in Value Motivation (VM) predict burnout and ITL
      following training. METHOD: Participants were staff from a Mental Health (MH)
      organisation in Australia. They participated in the Collaborative Recovery
      Training Programme (CRTP) and completed pre- and post-measures of values, general
      health, burnout and ITL. RESULTS: Increasingly holding work values due to guilt
      and shame predicted higher burnout after training. Increases in intrinsically
      held values predicted less ITL after training. CONCLUSIONS: Attending to and
      clarifying VM's has the potential to decrease burnout and ITL. Training
      programmes should focus on understanding the importance of values in reducing
      burnout and turnover rates among MH professionals.

PMID- 24433192
TI  - Prevalence of and factors associated with distraction among public transit bus
      drivers.
AB  - OBJECTIVE: Recent research has suggested that driver distraction is a major cause
      of driving performance impairment and motor vehicle collisions. Research on the
      topic has focused on passenger vehicles, with studies suggesting that drivers may
      be distracted nearly 33 percent of the time spent driving. To date, no study has
      examined the prevalence of distraction specifically among public transit bus
      drivers. METHODS: Over a 3-month period, trained investigators observed and
      recorded distraction behaviors of bus drivers. Distraction prevalence was
      compared by route characteristics (e.g., geographic area, travel speed) using chi
      square test. A general estimating equation logistic regression was used to
      estimate P values for distraction prevalence by driver demographics. RESULTS:
      Overall, there was a 39 percent prevalence of distraction. The most prevalent
      distractions were due to interactions with another passenger. Distractions were
      more prevalent among drivers <30 years of age or >= 50 years of age, on city
      streets or highways (relative to residential streets), and when there were more
      than 20 passengers. Distractions were the least prevalent in suburban areas, with
      the highest prevalence observed in city centers and rural areas. CONCLUSIONS:
      Driver distraction is a common problem for public transit bus drivers, mainly due
      to other passengers. Drivers should be educated on the hazards of distracted
      driving and on ways to avoid distraction.

PMID- 24433194
TI  - Effect of azithromycin mass drug administration for trachoma on spleen rates in
      Gambian children.
AB  - OBJECTIVE: To assess the effect of azithromycin mass drug administration regimens
      on spleen rates in children aged 0-5 years. METHODS: Clinical assessment of
      spleen size was carried out during a cluster-randomised trial of azithromycin
      mass treatment for trachoma elimination in The Gambia. Twenty-four communities
      received three annual mass treatments with azithromycin, and 24 communities
      received treatment at baseline only. RESULTS: At the 30-month follow-up, 3646
      children aged 0-5 years had spleen examination and measurement. Palpable
      splenomegaly was significantly lower in annually treated vs. baseline-only
      treatment communities and in treated vs. untreated children at 24 months in the
      annual treatment arm. CONCLUSION: The results suggest an effect of azithromycin
      on spleen rates at the individual level and are most plausibly due to the
      antimalarial effects of azithromycin.

PMID- 24433196
TI  - Post scriptum to the biography of Monsieur Leborgne.
AB  - In 1861, Paul Broca presented a case of a patient who had almost completely lost
      the ability of speech production. This patient is known as "Monsieur Leborgne"
      alias "Tan." In describing the history of his disease, Broca reported that
      Leborgne had spent a total of 21 years in hospitals. The article features new
      information on the history of Leborgne's hospitalization. 

PMID- 24433201
TI  - Selective alkylation and arylation of C-F bond with Grignard reagents.
AB  - Selective alkylation and arylation of the C-F bonds of polyfluoroaryl imines with
      Grignard reagents were discovered in the absence of metal catalysts. The aldazine
      N atom as an anchoring group has a special effect on the regioselectivity of the
      reaction. The C?N bond addition reaction with Grignard reagents was also
      explored. A possible mechanism was proposed on the competition between the
      nucleophilic substitution and addition reaction. 

PMID- 24433202
TI  - Mean platelet volume in hypertensive urgencies and emergencies: opening the
      Pandora's Box.

PMID- 24433203
TI  - Histamine in migraine and brain.
AB  - BACKGROUND: Histamine has been studied in both health and disease since the
      initial description a century ago. With its vasodilative effect, it was suggested
      early on to be involved in the pathophysiology of migraine. Over the past 25
      years, much has been learned about histamine as a neurotransmitter in the central
      nervous system. The role of this neurotransmitter system in migraine has not been
      previously reviewed. OBJECTIVE: Discuss a potential role of the brain
      histaminergic system in migraine. METHODS: Unstructured literature search with a
      no specific hypothesis-driven approach. RESULTS: There is substantial evidence
      that systemically given histamine may elicit, maintain, and aggravate headache.
      The mechanisms for this are not known, and histamines do not penetrate the blood
      brain barrier (BBB). However, circulating histamine may influence hypothalamic
      activity via the circumventricular organs that lack BBB. In the rat, prolonged
      activation of meningeal nociceptors induced by dural mast cell degranulation has
      been observed. Subcutaneous injections of N-alpha-methyl histamine, a catabolite
      of histamine with high affinity to the histamine H3 receptor, probably have some
      migraine preventive effect. A negative feedback on histamine release from mast
      cells in proximity to C-fiber endings has been a postulated mechanism. Most
      antihistamines have shown to be ineffective as acute medication for migraine. Two
      centrally acting potent H1 receptor antagonists (cinnarizine and cyproheptadine)
      have been reported to be efficacious in preventing migraine. However, the proof
      for this is limited, and their efficacy has been ascribed other actions than the
      antihistaminergic. In general, lack of specificity and side effects limit the
      potential use of centrally acting H1 and H2 antagonists. Brain histamine is
      synthesized by neurons that are restricted to the posterior basal hypothalamus,
      more specific to the tuberomamillary nucleus (TMN), and that project practically
      to the whole central nervous system. The posterior hypothalamus is a suspected
      locus in quo in several primary headaches. Recently, a positron emission
      tomography study performed in the prodromal phase of migraine attacks supported
      the idea of initial involvement of this area. In another recent study, the
      thalamic nuclei receiving trigeminal output was also shown to have direct
      connections with the ventral TMN. The central histaminergic system plays an
      important role in the complex sleep-wake cycle, promoting cortical excitability
      during wakening and attention, and it consolidates the wake state. The period of
      the day, in the evenings and during the night, when there is reduced
      susceptibility for migraine attacks corresponds with less central histaminergic
      firing. Activation of both the H3 and the H4 receptor promotes inhibitory actions
      on neurons. The H3 receptor causes autoinhibition of the histaminergic neurons
      themselves, and centrally acting H3 receptor agonist prodrugs have shown to both
      inhibit neurogenic inflammation in dura, to induce sleep, and to produce
      antinociception. There are no registered ongoing studies on H3 and H4 receptor
      ligands in migraine. CONCLUSION: The role of the central histaminergic system in
      migraine is largely unexplored, but findings from preclinical research may be
      linked to several aspects of the disorder. The histaminergic system of the brain
      may play an important role, especially in the initial phase of an attack, and
      histamine H3 and H4 receptor ligands may potentially have migraine prophylactic
      properties. However, the basis for this is still circumstantial, and the evidence
      is lacking.

PMID- 24433204
TI  - Taste clusters of music and drugs: evidence from three analytic levels.
AB  - This article examines taste clusters of musical preferences and substance use
      among adolescents and young adults. Three analytic levels are considered: fixed
      effects analyses of aggregate listening patterns and substance use in US radio
      markets, logistic regressions of individual genre preferences and drug use from a
      nationally representative survey of US youth, and arrest and seizure data from a
      large American concert venue. A consistent picture emerges from all three levels:
      rock music is positively associated with substance use, with some substance
      specific variability across rock sub-genres. Hip hop music is also associated
      with higher use, while pop and religious music are associated with lower use.
      These results are robust to fixed effects models that account for changes over
      time in radio markets, a comprehensive battery of controls in the individual
      level survey, and concert data establishing the co-occurrence of substance use
      and music listening in the same place and time. The results affirm a rich
      tradition of qualitative and experimental studies, demonstrating how symbolic
      boundaries are simultaneously drawn around music and drugs. 

PMID- 24433205
TI  - Complex and shifting interactions of phytochromes regulate fruit development in
      tomato.
AB  - Tomato fruit ripening is a complex metabolic process regulated by a genetical
      hierarchy. A subset of this process is also modulated by light signalling, as
      mutants encoding negative regulators of phytochrome signal transduction show
      higher accumulation of carotenoids. In tomato, phytochromes are encoded by a
      multi-gene family, namely PHYA, PHYB1, PHYB2, PHYE and PHYF; however, their
      contribution to fruit development and ripening has not been examined. Using
      single phytochrome mutants phyA, phyB1 and phyB2 and multiple mutants phyAB1,
      phyB1B2 and phyAB1B2, we compared the on-vine transitory phases of ripening until
      fruit abscission. The phyAB1B2 mutant showed accelerated transitions during
      ripening, with shortest time to fruit abscission. Comparison of transition
      intervals in mutants indicated a phase-specific influence of different
      phytochrome species either singly or in combination on the ripening process.
      Examination of off-vine ripened fruits indicated that ripening-specific
      carotenoid accumulation was not obligatorily dependent upon light and even dark
      incubated fruits accumulated carotenoids. The accumulation of transcripts and
      carotenoids in off-vine and on-vine ripened mutant fruits indicated a complex and
      shifting phase-dependent modulation by phytochromes. Our results indicate that,
      in addition to regulating carotenoid levels in tomato fruits, phytochromes also
      regulate the time required for phase transitions during ripening. 

PMID- 24433206
TI  - The humankind genome: from genetic diversity to the origin of human diseases.
AB  - Genome-wide association studies have failed to establish common variant risk for
      the majority of common human diseases. The underlying reasons for this failure
      are explained by recent studies of resequencing and comparison of over 1200 human
      genomes and 10 000 exomes, together with the delineation of DNA methylation
      patterns (epigenome) and full characterization of coding and noncoding RNAs
      (transcriptome) being transcribed. These studies have provided the most
      comprehensive catalogues of functional elements and genetic variants that are now
      available for global integrative analysis and experimental validation in
      prospective cohort studies. With these datasets, researchers will have
      unparalleled opportunities for the alignment, mining, and testing of hypotheses
      for the roles of specific genetic variants, including copy number variations,
      single nucleotide polymorphisms, and indels as the cause of specific phenotypes
      and diseases. Through the use of next-generation sequencing technologies for
      genotyping and standardized ontological annotation to systematically analyze the
      effects of genomic variation on humans and model organism phenotypes, we will be
      able to find candidate genes and new clues for disease's etiology and treatment.
      This article describes essential concepts in genetics and genomic technologies as
      well as the emerging computational framework to comprehensively search websites
      and platforms available for the analysis and interpretation of genomic data.

PMID- 24433207
TI  - Genetic diversity of the rice bean (Vigna umbellata) genepool as assessed by SSR
      markers.
AB  - The genetic diversity of 472 rice bean accessions (388 cultivated and 84 wild)
      from 16 Asian countries was evaluated by 13 simple sequence repeat (SSR) markers.
      In total, 168 alleles were detected, and the numbers of alleles in cultivated and
      wild accessions were 129 and 132, respectively. The gene diversity in cultivated
      populations (0.565) was about 83% of that for wild (0.678) populations.
      Cultivated populations from Vietnam, Myanmar, Nepal, and India had the highest
      gene diversity (>0.5). East Asian accessions formed a distinct genepool.
      Indonesian cultivated accessions showed high genetic divergence from other
      cultivated populations and had the most similar genetic structure to wild
      accessions. In Nepalese cultivated accessions, many accessions from western
      regions were quite distinct from others and formed a specific group. These
      Nepalese accessions could be considered a unique gene source for rice bean
      breeding. In contrast, eastern Nepalese accessions showed an SSR profile similar
      to that of Southeast Asian rice beans. The present study represents the first
      comprehensive SSR analysis in cultivated and wild rice bean germplasm and
      clarifies geographical distribution of genetic profile that might be used to
      broaden the genetic base of currently grown rice bean cultivars.

PMID- 24433208
TI  - Random DNA libraries from three species of the stick insect genus Bacillus
      (Insecta: Phasmida): repetitive DNA characterization and first observation of
      polyneopteran MITEs.
AB  - The repetitive DNA content of the stick insect species Bacillus rossius
      (facultative parthenogenetic), Bacillus grandii (gonochoric), and Bacillus
      atticus (obligate parthenogenetic) was analyzed through the survey of random
      genomic libraries roughly corresponding to 0.006% of the genome. By repeat
      masking, 19 families of transposable elements were identified (two LTR and six
      non-LTR retrotransposons; 11 DNA transposons). Moreover, a de novo analysis
      revealed, among the three libraries, the first MITE family observed in
      polyneopteran genomes. On the whole, transposable element abundance represented
      23.3% of the genome in B. rossius, 22.9% in B. atticus, and 18% in B. grandii.
      Tandem repeat content in the three libraries is much lower: 1.32%, 0.64%, and
      1.86% in B. rossius, B. grandii, and B. atticus, respectively. Microsatellites
      are the most abundant in all species. Minisatellites were only found in B.
      rossius and B. atticus, and five monomers belonging to the Bag320 satellite
      family were detected in B. atticus. Assuming the survey provides adequate
      representation of the relative genome, the obligate parthenogenetic species (B.
      atticus), compared with the other two species analyzed, does not show a lower
      transposable element content, as expected from some theoretical and empirical
      studies.

PMID- 24433209
TI  - Sequencing and annotation of the chloroplast DNAs and identification of
      polymorphisms distinguishing normal male-fertile and male-sterile cytoplasms of
      onion.
AB  - Male-sterile (S) cytoplasm of onion is an alien cytoplasm introgressed into onion
      in antiquity and is widely used for hybrid seed production. Owing to the biennial
      generation time of onion, classical crossing takes at least 4 years to classify
      cytoplasms as S or normal (N) male-fertile. Molecular markers in the organellar
      DNAs that distinguish N and S cytoplasms are useful to reduce the time required
      to classify onion cytoplasms. In this research, we completed next-generation
      sequencing of the chloroplast DNAs of N- and S-cytoplasmic onions; we assembled
      and annotated the genomes in addition to identifying polymorphisms that
      distinguish these cytoplasms. The sizes (153 538 and 153 355 base pairs) and GC
      contents (36.8%) were very similar for the chloroplast DNAs of N and S
      cytoplasms, respectively, as expected given their close phylogenetic
      relationship. The size difference was primarily due to small indels in intergenic
      regions and a deletion in the accD gene of N-cytoplasmic onion. The structures of
      the onion chloroplast DNAs were similar to those of most land plants with large
      and small single copy regions separated by inverted repeats. Twenty-eight single
      nucleotide polymorphisms, two polymorphic restriction-enzyme sites, and one indel
      distributed across 20 chloroplast genes in the large and small single copy
      regions were selected and validated using diverse onion populations previously
      classified as N or S cytoplasmic using restriction fragment length polymorphisms.
      Although cytoplasmic male sterility is likely associated with the mitochondrial
      DNA, maternal transmission of the mitochondrial and chloroplast DNAs allows for
      polymorphisms in either genome to be useful for classifying onion cytoplasms to
      aid the development of hybrid onion cultivars.

PMID- 24433210
TI  - Cytogenetics and characterization of microsatellite loci for a South American
      pioneer tree species, Croton floribundus.
AB  - Despite the recent advances in plant population genetic studies, the lack of
      information regarding pedigree, ploidy level, or mode of inheritance for many
      polyploids can compromise the analysis of the molecular data produced. The aim of
      this study was to examine both microsatellite and cytogenetic characteristics of
      the pioneer tree Croton floribundus Spreng. (Euphorbiaceae) to test for the
      occurrence of polyploidy in the species and to evaluate its implications for the
      appropriate use of SSR markers. Seven microsatellite markers were developed and
      screened for 62 individuals from a semi-deciduous tropical forest in Brazil.
      Chromosome number, meiotic behavior, and pollen viability were evaluated from
      male flower buds. All SSR loci were highly polymorphic. The number of bivalents
      observed in meiosis n = 56 (2n = 8* = 112) and the maximum number of alleles per
      individual (Ni = 8) demonstrated the occurrence of polyploidy in C. floribundus.
      The normal meiotic pairing and the high pollen viability suggested that C.
      floribundus is a regular and stable polyploid, most likely an allopolyploid. The
      combined SSR and cytogenetic data provided new evidence on the origin and
      evolution of the species as well as assured the accurate use of SSR loci for
      population genetic studies of the polyploid pioneer species.

PMID- 24433211
TI  - The Drosophila melanogaster septin gene Sep2 has a redundant function with the
      retrogene Sep5 in imaginal cell proliferation but is essential for oogenesis.
AB  - Septins are cytoskeletal proteins that form hetero-oligomeric complexes and
      function in many biological processes, including cytokinesis. Drosophila
      melanogaster has five septin genes. Sep5, which is the most recently evolved
      septin gene in Drosophila, is a retrogene copy of Sep2. Sep5 mutants appear wild
      type, whereas Sep2 mutant females are semisterile. Their ovaries have egg
      chambers containing abnormal numbers of nurse cells. The egg chamber phenotype is
      rescued to wild type by expressing a Sep2 cDNA, but it is only partially rescued
      by expressing a Sep5 cDNA, showing that these paralogs have diverged in function
      at the protein level. Sep2 Sep5 double mutants have an early pupal lethal
      phenotype and lack imaginal discs, suggesting that these genes have redundant
      functions during imaginal cell proliferation.

PMID- 24433213
TI  - Genetic component of flammability variation in a Mediterranean shrub.
AB  - Recurrent fires impose a strong selection pressure in many ecosystems worldwide.
      In such ecosystems, plant flammability is of paramount importance because it
      enhances population persistence, particularly in non-resprouting species. Indeed,
      there is evidence of phenotypic divergence of flammability under different fire
      regimes. Our general hypothesis is that flammability-enhancing traits are
      adaptive; here, we test whether they have a genetic component. To test this
      hypothesis, we used the postfire obligate seeder Ulex parviflorus from sites
      historically exposed to different fire recurrence. We associated molecular
      variation in potentially adaptive loci detected with a genomic scan (using AFLP
      markers) with individual phenotypic variability in flammability across fire
      regimes. We found that at least 42% of the phenotypic variation in flammability
      was explained by the genetic divergence in a subset of AFLP loci. In spite of
      generalized gene flow, the genetic variability was structured by differences in
      fire recurrence. Our results provide the first field evidence supporting that
      traits enhancing plant flammability have a genetic component and thus can be
      responding to natural selection driven by fire. These results highlight the
      importance of flammability as an adaptive trait in fire-prone ecosystems. 

PMID- 24433214
TI  - Hinokitiol is a novel glycoprotein VI antagonist on human platelets.
AB  - Hinokitiol (4-isopropyl-tropolone) is a bioactive compound with various
      pharmacological activities that is found in the wood of cupressaceous plants.
      Platelet activation plays an important role in thrombogenesis. In our previous
      study, hinokitiol specifically inhibited collagen-induced platelet aggregation ex
      vivo and prolonged thrombogenesis in vivo. The glycoprotein (GP) VI and integrin
      alpha2beta1 are major collagen receptors that mediate platelet adhesion and
      aggregation. In our current study, we investigated which of these collagen
      receptors is involved in the hinokitiol-mediated inhibition of platelet
      activation. Treatment with 2-100 uM hinokitiol caused a dose-dependent right,
      parallel shift in the collagen concentration-response curve (0.5-10 ug/ml), with
      no change in the maximal responses. Furthermore, hinokitiol inhibited platelet
      aggregation and relative [Ca(2+)]i mobilization stimulated by convulxin, an
      agonist of GP VI, but not by aggretin, an agonist of integrin alpha2beta1,
      indicating that hinokitiol mediates the inhibition of platelet activation through
      GP VI, rather than through integrin alpha2beta1. Hinokitiol also specifically
      inhibited the convulxin-mediated activation of protein kinase C, phospholipase
      Cgamma2, Akt, mitogen-activated protein kinases, and Lyn. Hinokitiol markedly
      diminished the co-immunoprecipitation of GP VI-bound Lyn after convulxin
      stimulation. In conclusion, hinokitiol, an antagonist of collagen GP VI may
      represent a novel antiplatelet drug for the prevention of thrombi associated with
      coronary and cerebral artery diseases.

PMID- 24433215
TI  - Risk of herpes zoster in psoriatic patients undergoing biologic treatment.
AB  - The advent of biologic treatments for psoriasis has many benefits, such as
      considerably improved efficacy and lower frequency of organ toxicity. While the
      frequency of organ dysfunction during biologic treatment is considered to be low,
      the incidence of infection is slightly higher. Patients on biologic treatments
      are regularly monitored to be able to detect the onset of infection, because
      there is evidence of an increase in the risk of bacterial and fungal infections
      during treatment. A total of 144 patients who had received biologic treatment for
      a year were retrospectively examined. We encountered four cases, including one of
      39 patients on infliximab treatment, two of 65 patients on adalimumab treatment
      and one of 40 patients on ustekinumab treatment, who developed herpes zoster (HZ)
      within 1 year of starting biologic treatment. Our experience shows that this
      incidence could be higher than that in the general population, although the data
      is retrospective. On consideration of previous studies and our own experiences,
      the risk of HZ occurrence during biologic treatments for psoriasis may increase. 

PMID- 24433219
TI  - Repair of idiopathic dilatation of the right atrium.
AB  - Idiopathic dilatation of the right atrium is a rare cardiac anomaly. The surgical
      management of this rare cardiac anomaly is reviewed.

PMID- 24433216
TI  - Review article: Linaclotide for the management of irritable bowel syndrome with
      constipation.
AB  - BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) represents a
      significant burden to patients and healthcare systems due to its prevalence and
      lack of successful symptomatic resolution with established treatment options.
      Linaclotide 290 MUg has recently been approved by the European Medicines Agency
      (EMA) for moderate-to-severe IBS-C and by the US Food and Drug Administration for
      IBS-C (290 MUg dose) and for chronic constipation (145 MUg dose). AIM: To
      summarise data leading to the approval of linaclotide for IBS-C, with focus on
      EMA-pre-specified outcome measures. METHODS: Literature search of a peer-review
      database (PubMed) and review of congress abstracts on linaclotide preclinical and
      clinical trial data in IBS-C. RESULTS: Preclinical studies suggest that the
      guanylate cyclase C agonist (GCCA) linaclotide acts through elevation of cyclic
      guanosine monophosphate (cGMP) levels, leading to accelerated gastrointestinal
      (GI) transit through increased fluid secretion and reduced visceral
      hypersensitivity. Clinical trial data demonstrate that linaclotide improves
      abdominal symptoms (pain, bloating) and bowel symptoms (constipation) compared
      with placebo in patients with IBS-C. The most frequent side effect, diarrhoea,
      results from the therapeutic action of linaclotide. Linaclotide acts locally in
      the GI tract with minimal systemic exposure, resulting in low oral
      bioavailability and thus a low risk of relevant systemic adverse effects.
      CONCLUSION: Linaclotide, a first-in-class GCCA, is a promising new drug with a
      novel, dual mechanism of action that, unlike more well-established agents, can
      relieve the abdominal pain, bloating and constipation associated with IBS-C and
      has a low propensity for systemic side effects.

PMID- 24433217
TI  - Liposomal amphotericin B for complicated visceral leishmaniasis (kala-azar) in
      eastern Sudan: how effective is treatment for this neglected disease?
AB  - OBJECTIVES: The aim of this study was to report the patient profile and treatment
      outcomes, including relapses, of patients with visceral leishmaniasis (VL)
      treated with liposomal amphotericin B (AmBisome) in Gedaref, Sudan. METHODS:
      AmBisome was offered to two groups of patients: primary VL patients with specific
      criteria (age <=2 or >=45 years, advanced clinical disease, pregnancy, HIV co
      infection and contraindications for antimonials) and VL relapses. AmBisome was
      given at a total dose of 30 mg/kg, over 10 days. Slow responders received up to
      50 mg/kg. Treatment failure was confirmed parasitologically. Standardised
      treatment outcomes were assessed. RESULTS: Between March 2010 and June 2012, a
      total of 281 (74%) patients with primary VL and 98 (26%) patients with VL
      relapses received AmBisome (54% male, median age = 11 years, interquartile range
      2-30). End-of-treatment outcomes for primary VL were 260 (92%) initial cure
      including three (1%) slow responders, three (1%) treatment failures, 14 (5%)
      deaths and four (1%) unknown outcomes. Outcomes for VL relapses were 92 (94%)
      initial cure with five (5%) slow responders, four (4%) treatment failures, one
      (1%) death and one (1%) unknown outcome. At 6 months, there were 19 (7%) relapses
      amongst primary VL and 10 (10%) VL relapses had a new relapse. Loss to follow-up
      in both groups was 38%. None of the deaths that occurred during the study period
      was attributed to AmBisome. CONCLUSION: AmBisome appears to be effective for
      initial cure of VL and the drug seems safe, but is expensive (400 USD/treatment).
      Sustained mechanisms to allow improved access of this expensive drug particularly
      in East Africa are urgently needed. Relapses and losses to follow-up require
      specific investigation.

PMID- 24433220
TI  - Primary somatosensory cortex hand representation dynamically modulated by motor
      output.
AB  - The brain's primary motor and primary somatosensory cortices are generally viewed
      as functionally distinct entities. Here we show by means of
      magnetoencephalography with a phantom-limb patient, that movement of the phantom
      hand leads to a change in the response of the primary somatosensory cortex to
      tactile stimulation. This change correlates with the described conscious
      perception and suggests a greater degree of functional unification between the
      primary motor and somatosensory cortices than is currently realized. We suggest
      that this may reflect the evolution of this part of the human brain, which is
      thought to have occurred from an undifferentiated sensorimotor cortex. 

PMID- 24433222
TI  - In reply.

PMID- 24433221
TI  - CGX1037 is a novel PKC isoform delta selective inhibitor in platelets.
AB  - Platelets upon activation change their shape, aggregate and secrete alpha and
      dense granule contents among which ADP acts as a feedback activator. Different
      Protein Kinase C (PKC) isoforms have specific non-redundant roles in mediating
      platelet responses including secretion and thrombus formation. Murine platelets
      lacking specific PKC isoforms have been used to evaluate the isoform specific
      functions. Novel PKC isoform delta has been shown to play an important role in
      some pathological processes. Lack of specific inhibitors for PKCdelta has
      restricted analysis of its role in various cells. The current study was carried
      out to evaluate a novel small molecule PKCdelta inhibitor, CGX1037 in platelets.
      Platelet aggregation, dense granule secretion and western blotting experiments
      were performed to evaluate CGX1037. In human platelets, CGX1037 inhibited PAR4
      mediated phosphorylation on PKD2, a PKCdelta-specific substrate. Pre-treatment of
      human or murine platelets with CGX1037 inhibited PAR4-mediated dense granule
      secretion whereas it potentiated GPVI-mediated dense granule secretion similar to
      the responses observed in murine platelets lacking PKCdelta. Furthermore, pre
      treatment of platelets from PKCdelta(-/-) mice with CGX1037 had no significant
      additive effect on platelet responses suggesting the specificity of CGX1037.
      Hence, we show that CGX1037 is a selective small molecule inhibitor of PKCdelta
      in platelets.

PMID- 24433223
TI  - Effects of topical diclofenac plus heparin (DHEP+H plaster) on somatic pain
      sensitivity in healthy subjects with a latent algogenic condition of the lower
      limb.
AB  - OBJECTIVE: To evaluate whether a diclofenac epolamine + heparin topical (plaster)
      is more effective than diclofenac plaster alone in reducing deep somatic
      hyperalgesia in subjects without spontaneous pain and whether the effect is
      linked to or independent of the anti-edematous action of heparin. DESIGN:
      Prospective, double-blind, randomized and controlled, four-arm parallel design
      trial. SUBJECTS: One hundred and four patients (84 women, 20 men, mean age 42.2
      +/- 13.3 years), with deep somatic hyperalgesia in one thigh, randomly assigned
      to one of 4 groups of 26 each. INTERVENTION: Each group underwent one of the
      following plaster treatments on one thigh: diclofenac+heparin; diclofenac;
      heparin; placebo, for 7 days, renewing the plaster every 24 hours. OUTCOME
      MEASURES: Before treatment (day 1), at day 4 and day 8, assessment of (a)
      pressure and electrical pain thresholds of vastus lateralis and overlying
      subcutis and skin; and (b) structure/thickness of subcutis and muscle with
      ultrasounds at the same level. RESULTS: During treatment, in placebo and heparin,
      no significant threshold changes, except subcutis thresholds which increased
      slightly (P < 0.02); in diclofenac and diclofenac+heparin, significant increase
      in all thresholds (0.0001 < P < 0.04). Electrical muscle pain thresholds
      increased significantly more in diclofenac+heparin than in diclofenac, heparin,
      and placebo (0.0001 < P < 0.04). In all groups: no edema and thickness changes at
      ultrasounds in muscle and subcutis. CONCLUSIONS: Topical diclofenac+heparin is
      significantly more effective than diclofenac alone in reducing muscle
      hyperalgesia in subjects without spontaneous pain, independently of the anti
      edematous action of heparin. The results provide a rationale for the use of
      diclofenac+heparin also in algogenic conditions without evident signs of
      injury/edema/hematoma.

PMID- 24433224
TI  - Synthesis and evaluation of chalcone derivatives as inhibitors of neutrophils'
      chemotaxis, phagocytosis and production of reactive oxygen species.
AB  - Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of
      reactive oxygen species (ROS) are among the important targets in developing anti
      inflammatory agents and immunosuppressants. Eight series of chalcone derivatives
      including five newly synthesized series were assessed for their inhibitory
      effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear
      neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities
      were investigated using the Boyden chamber technique and the Phagotest kit,
      respectively, while ROS production was evaluated using luminol- and lucigenin
      based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4
      methylaminoethanol functional group were active in all the assays performed. It
      was also observed that some of the compounds were active in inhibiting chemotaxis
      while others suppressed phagocytosis and ROS production. The information obtained
      gave new insight into chalcone derivatives with the potential to be developed as
      immunomodulators. 

PMID- 24433225
TI  - Two cases of nevus sebaceous accompanying secondary tumors with betaKlotho
      expression.

PMID- 24433226
TI  - Social knowledge facilitates chunking in infancy.
AB  - Two experiments investigated whether infants can use their rich social knowledge
      to bind representations of individual objects into larger social units, thereby
      overcoming the three-item limit of working memory. In Experiment 1, 16-month-olds
      (n = 32) remembered up to four hidden dolls when the dolls had faced and
      interacted with each other in pairs, but not when they faced and interacted with
      the infant, suggesting that infants chunked the dolls into social pairs. In
      Experiment 2 (n = 16), infants failed to remember four dolls when they faced each
      other without interacting, indicating that interaction between the dolls was
      necessary to drive chunking. This work bridges a gap between social cognition and
      memory by demonstrating that infants can use social cues to expand memory. 

PMID- 24433227
TI  - Risk factor selection in rate making: EM adaptive LASSO for zero-inflated poisson
      regression models.
AB  - Risk factor selection is very important in the insurance industry, which helps
      precise rate making and studying the features of high-quality insureds. Zero
      inflated data are common in insurance, such as the claim frequency data, and zero
      inflation makes the selection of risk factors quite difficult. In this article,
      we propose a new risk factor selection approach, EM adaptive LASSO, for a zero
      inflated Poisson regression model, which combines the EM algorithm and adaptive
      LASSO penalty. Under some regularity conditions, we show that, with probability
      approaching 1, important factors are selected and the redundant factors are
      excluded. We investigate the finite sample performance of the proposed method
      through a simulation study and the analysis of car insurance data from SAS
      Enterprise Miner database. 

PMID- 24433228
TI  - Reconstructing the infected aortic root with antibiotic impregnated biological
      glue.
AB  - Prosthetic valve dehiscence and persistent infection are two complications
      following reconstruction of the aortic root in destructive endocarditis. A
      technique is described involving the principles of aggressive debridement,
      closure of large abscess cavities with biological material incorporating a slurry
      of antibiotic-impregnated biological sealant, and replacement of the aortic valve
      with an aortic allograft valve. This strategy appears to have been successful in
      preventing persistent endocarditis and valve dehiscence in a limited number of
      patients.

PMID- 24433229
TI  - Recruitment and retention of young women into nutrition research studies:
      practical considerations.
AB  - BACKGROUND: Successful recruitment and retention of participants into research
      studies is critical for optimising internal and external validity. Research into
      diet and lifestyle of young women is important due to the physiological
      transitions experienced at this life stage. This paper aims to evaluate data
      related to recruitment and retention across three research studies with young
      women, and present practical advice related to recruiting and retaining young
      women in order to optimise study quality within nutrition research. METHODS:
      Recruitment and retention strategies used in three nutrition studies that
      targeted young women (18 to 35 years) were critiqued. A randomised controlled
      trial (RCT), a crossover validation study and a cross-sectional survey were
      conducted at the University of Newcastle, Australia between 2010 and
      2013Successful recruitment was defined as maximum recruitment relative to time.
      Retention was assessed as maximum participants remaining enrolled at study
      completion. RESULTS: Recruitment approaches included notice boards, web and
      social network sites (Facebook and Twitter), with social media most successful in
      recruitment. The online survey had the highest recruitment in the shortest time
      frame (751 participants in one month). Email, phone and text message were used in
      study one (RCT) and study two (crossover validation) and assisted in low
      attrition rates, with 93% and 75.7% completing the RCT and crossover validation
      study respectively. Of those who did not complete the RCT, reported reasons were:
      being too busy; and having an unrelated illness. CONCLUSION: Recruiting young
      women into nutrition research is challenging. Use of social media enhances
      recruitment, while Email, phone and text message contact improves retention
      within interventions. Further research comparing strategies to optimise
      recruitment and retention in young women, including flexible testing times,
      reminders and incentives is warranted.

PMID- 24433230
TI  - Goodstart: a cluster randomised effectiveness trial of an integrated, community
      based package for maternal and newborn care, with prevention of mother-to-child
      transmission of HIV in a South African township.
AB  - BACKGROUND: Progress towards MDG4 for child survival in South Africa requires
      effective prevention of mother-to-child transmission (PMTCT) of HIV including
      increasing exclusive breastfeeding, as well as a new focus on reducing neonatal
      deaths. This necessitates increased focus on the pregnancy and early post-natal
      periods, developing and scaling up appropriate models of community-based care,
      especially to reach the peri-urban poor. METHODS: We used a randomised controlled
      trial with 30 clusters (15 in each arm) to evaluate an integrated, scalable
      package providing two pregnancy visits and five post-natal home visits delivered
      by community health workers in Umlazi, Durban, South Africa. Primary outcomes
      were exclusive and appropriate infant feeding at 12 weeks post-natally and HIV
      free infant survival. RESULTS: At 12 weeks of infant age, the intervention was
      effective in almost doubling the rate of exclusive breastfeeding (risk ratio
      1.92; 95% CI: 1.59-2.33) and increasing infant weight and length-for-age z-scores
      (weight difference 0.09; 95% CI: 0.00-0.18, length difference 0.11; 95% CI: 0.03
      0.19). No difference was seen between study arms in HIV-free survival. Women in
      the intervention arm were also more likely to take their infant to the clinic
      within the first week of life (risk ratio 1.10; 95% CI: 1.04-1.18). CONCLUSIONS:
      The trial coincided with national scale up of ARVs for PMTCT, and this could have
      diluted the effect of the intervention on HIV-free survival. We have demonstrated
      that implementation of a pro-poor integrated PMTCT and maternal, neonatal and
      child health home visiting model is feasible and effective. This trial could
      inform national primary healthcare reengineering strategies in favour of home
      visits. The dose effect on exclusive breastfeeding is notable as improving
      exclusive breastfeeding has been resistant to change in other studies targeting
      urban poor families.

PMID- 24433231
TI  - Meeting the information needs of lower income cancer survivors: results of a
      randomized control trial evaluating the american cancer society's "I can cope".
AB  - The American Cancer Society is a leader in the development of cancer survivorship
      resources. One resource of the American Cancer Society is the I Can Cope program,
      an educational program for cancer survivors and their families. Evaluations of
      this program indicate that cancer patients highly rate its objectives. Yet, there
      are gaps in the understanding of the full impact of the program on diverse cancer
      survivors. In this study, the authors used a randomized trial to evaluate the
      program. Participants included 140 low-income survivors (79% Black; 38% breast
      cancer) from community hospitals who were randomized to 4 sessions of I Can Cope
      (learning about cancer; understanding cancer treatments; relieving cancer pain;
      and keeping well in mind and body) or 4 sessions of a wellness intervention
      (humor, meditation, relaxation, and music therapy). The authors' primary outcome
      was "met information needs." After controlling for covariates, their analysis
      indicated that I Can Cope was no more effective than the wellness intervention in
      addressing survivor information needs relative to the learning objectives.
      Participants provided high overall ratings for both interventions. Self-efficacy
      for obtaining advice about cancer, age, education, and income were associated
      with information needs. Educational programs tailored to levels of self-efficacy
      and patient demographics may be needed. 

PMID- 24433232
TI  - A platelet P-selectin test predicts adverse cardiovascular events in patients
      with acute coronary syndromes treated with aspirin and clopidogrel.
AB  - There is wide variation in response to antiplatelet therapy and high on-treatment
      platelet reactivity is associated with adverse cardiovascular events. The
      objective here was to determine whether the results of a novel strategy for
      assessing platelet reactivity (based on P-selectin measurement) are associated
      with clinical outcomes in patients with acute coronary syndromes (ACS). This was
      a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel. P
      selectin tests designed to assess response to P2Y12 antagonists or aspirin were
      performed alongside light transmission aggregometry. For the P2Y12 P-selectin
      test, an optimal cutoff for high platelet reactivity was determined by receiver
      operating characteristic (ROC) curve analysis. Patients were divided into two
      cohorts based on this value: patients with (n = 42) or without (n = 58) high
      platelet reactivity. The primary endpoint was defined as the composite of
      cardiovascular death, myocardial infarction and stent thrombosis. After 12
      months, the primary endpoint occurred in 12 patients. ROC curve analysis
      determined that the P2Y12 P-selectin test results were predictive of the primary
      endpoint (area under curve = 0.69, p = 0.046). The primary endpoint occurred more
      frequently in patients with high on-treatment platelet reactivity compared to
      those without (21.4% vs. 5.2%; hazard ratio (HR) 4.14; p = 0.026). The P2Y12 P
      selectin test results correlated with light transmission aggregometry (Spearman p
      < 0.0001). Using the Aspirin P-selectin test, only two patients demonstrated high
      on-treatment platelet reactivity. This study suggests that a P2Y12 P-selectin
      test is capable of detecting high on-treatment platelet reactivity, which is
      associated with subsequent cardiovascular events.

PMID- 24433233
TI  - Cadmium induces two waves of reactive oxygen species in Glycine max (L.) roots.
AB  - Cadmium (Cd) is a non-essential heavy metal that may be toxic or even lethal to
      plants as it can be easily taken up by the roots and loaded into the xylem to the
      leaves. Using soybean roots (Glycine max L.) DM 4800, we have analysed various
      parameters related to reactive oxygen metabolism and nitric oxide (NO) during a 6
      day Cd exposure. A rise in H(2)O(2) and NO, and to a lesser extent O(2)(.-)
      content was observed after 6 h exposure with a concomitant increase in lipid
      peroxidation and carbonyl group content. Both oxidative markers were
      significantly reduced after 24 h. A second, higher wave of O(2)(.-) production
      was also observed after 72 h of exposure followed by a reduction until the end of
      the treatment. NOX and glicolate oxidase activity might be involved in the
      initial Cd-induced reactive oxygen species (ROS) production and it appears that
      other sources may also participate. The analysis of antioxidative enzymes showed
      an increase in glutathione-S-transferase activity and in transcript levels and
      activity of enzymes involved in the ascorbate-glutathione cycle and the NADPH
      generating enzymes. These results suggest that soybean is able to respond rapidly
      to oxidative stress imposed by Cd by improving the availability of NADPH
      necessary for the ascorbate-glutathione cycle.

PMID- 24433234
TI  - Randomized clinical trial of the Timing it Right Stroke Family Support Program:
      research protocol.
AB  - BACKGROUND: Family caregivers provide invaluable support to stroke survivors
      during their recovery, rehabilitation, and community re-integration.
      Unfortunately, it is not standard clinical practice to prepare and support
      caregivers in this role and, as a result, many experience stress and poor health
      that can compromise stroke survivor recovery and threaten the sustainability of
      keeping the stroke survivor at home. We developed the Timing it Right Stroke
      Family Support Program (TIRSFSP) to guide the timing of delivering specific types
      of education and support to meet caregivers' evolving needs. The objective of
      this multi-site randomized controlled trial is to determine if delivering the
      TIRSFSP across the stroke care continuum improves caregivers' sense of being
      supported and emotional well-being. METHODS/DESIGN: Our multi-site single-blinded
      randomized controlled trial will recruit 300 family caregivers of stroke
      survivors from urban and rural acute care hospitals. After completing a baseline
      assessment, participants will be randomly allocated to one of three groups: 1)
      TIRSFSP guided by a stroke support person (health care professional with stroke
      care experience), delivered in-person during acute care and by telephone for
      approximately the first six to 12 months post-stroke, 2) caregiver self-directed
      TIRSFSP with an initial introduction to the program by a stroke support person,
      or 3) standard care receiving the educational resource "Let's Talk about Stroke"
      prepared by the Heart and Stroke Foundation. Participants will complete three
      follow-up quantitative assessments 3, 6, and 12-months post-stroke. These include
      assessments of depression, social support, psychological well-being, stroke
      knowledge, mastery (sense of control over life), caregiving assistance provided,
      caregiving impact on everyday life, and indicators of stroke severity and
      disability. Qualitative methods will also be used to obtain information about
      caregivers' experiences with the education and support received and the impact on
      caregivers' perception of being supported and emotional well-being. DISCUSSION:
      This research will determine if the TIRSFSP benefits family caregivers by
      improving their perception of being supported and emotional well-being. If proven
      effective, it could be recommended as a model of stroke family education and
      support that meets the Canadian Stroke Best Practice Guideline recommendation for
      providing timely education and support to families through transitions. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00958607.

PMID- 24433235
TI  - Lethal course of meconium ileus in preterm twins revealing a novel cystic
      fibrosis mutation (p.Cys524Tyr).
AB  - BACKGROUND: In term newborns meconium ileus is frequently associated with cystic
      fibrosis. Reports on meconium ileus in preterm infants being diagnosed with
      cystic fibrosis early after birth are very scarce. Associations between genotype
      and phenotype in cystic fibrosis and its particular comorbidities have been
      reported. CASE PRESENTATION: Two extremely preterm twin infants (26 weeks of
      gestation) born from a Malaysian mother and a Caucasian father were presented
      with typical signs of meconium ileus. Despite immediate surgery both displayed a
      unique and finally lethal course. Mutation analysis revealed a novel, probably
      pathogenic cystic fibrosis mutation, p.Cys524Tyr. The novel mutation might
      explain the severity of disease next to typical sequelae of prematurity.
      CONCLUSION: Preterm neonates with meconium ileus have to be evaluated for cystic
      fibrosis beyond ethnical boundaries, but may take devastating clinical courses
      despite early treatment. The novel, potentially pathogenic CF mutation
      p.Cys524Tyr might be associated with severe meconium ileus in neonates. Disease
      modifying loci are important targets for intestinal comorbidity of cystic
      fibrosis.

PMID- 24433237
TI  - Endophytic tumours do not constitute a barrier to robotic partial nephrectomy.

PMID- 24433236
TI  - Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages.
AB  - BACKGROUND: The molecular history of animal evolution from single-celled
      ancestors remains a major question in biology, and little is known regarding the
      evolution of cell cycle regulation during animal emergence. In this study, we
      conducted a comprehensive evolutionary analysis of CDK and cyclin proteins in
      metazoans and their unicellular relatives. RESULTS: Our analysis divided the CDK
      family into eight subfamilies. Seven subfamilies (CDK1/2/3, CDK5, CDK7, CDK 20,
      CDK8/19, CDK9, and CDK10/11) are conserved in metazoans and fungi, with the
      remaining subfamily, CDK4/6, found only in eumetazoans. With respect to cyclins,
      cyclin C, H, L, Y subfamilies, and cyclin K and T as a whole subfamily, are
      generally conserved in animal, fungi, and amoeba Dictyostelium discoideum. In
      contrast, cyclin subfamilies B, A, E, and D, which are cell cycle-related, have
      distinct evolutionary histories. The cyclin B subfamily is generally conserved in
      D. discoideum, fungi, and animals, whereas cyclin A and E subfamilies are both
      present in animals and their unicellular relatives such as choanoflagellate
      Monosiga brevicollis and filasterean Capsaspora owczarzaki, but are absent in
      fungi and D. discoideum. Although absent in fungi and D. discoideum, cyclin D
      subfamily orthologs can be found in the early-emerging, non-opisthokont apusozoan
      Thecamonas trahens. Within opisthokonta, the cyclin D subfamily is conserved only
      in eumetazoans, and is absent in fungi, choanoflagellates, and the basal metazoan
      Amphimedon queenslandica. CONCLUSIONS: Our data indicate that the CDK4/6
      subfamily and eumetazoans emerged simultaneously, with the evolutionary
      conservation of the cyclin D subfamily also tightly linked with eumetazoan
      appearance. Establishment of the CDK4/6-cyclin D complex may have been the key
      step in the evolution of cell cycle control during eumetazoan emergence.

PMID- 24433238
TI  - Rebalanced hemostasis in patients with idiopathic thrombocytopenic purpura.
AB  - Previous laboratory and clinical data have shown evidence for the concept of
      rebalanced hemostasis in liver disease. We evaluate whether this concept of
      rebalanced hemostasis can be applied in patients with idiopathic thrombocytopenic
      purpura (ITP). Twenty patients with ITP (platelet count < 100 * 10(9) /l) who
      visited our hospital were enrolled. We measured the von Willebrand factor (vWF)
      antigen levels and performed native blood thromboelastography (TEG) to evaluate
      the hemostasis. As a subgroup analysis, we compared patients with elevated vWF
      levels with those with normal levels. Bleeding symptoms of the patients were
      followed up for 6 months. The mean (SD [IQR]) platelet count was 44.23 * 10(9) /l
      (25.78 [27.00-60.50]). The following TEG parameters were within the normal range
      in most patients (number of patients with a normal value): clotting time (17),
      clot formation time (17), alpha-angle (15), maximum clot formation (10), and
      maximum lysis (12). The mean (SD) vWF antigen level (%) was 163% (80). There were
      eight patients (40%) with elevated vWF antigen levels [218% (104) vs. 126% (19),
      p = 0.007, elevated vs. normal patients, respectively]. Those with elevated vWF
      antigen levels were older [58 year (10) vs. 40 year (13), p = 0.004] and had a
      longer disease status [67 months (39) vs. 33 months (25), p = 0.028]. Although
      the platelet count was not different, the CFT was shorter [287 (104) vs. 561
      (291), p = 0.042] and the alpha-angle was larger [49 (6) vs. 34 (15), p = 0.033]
      in those with elevated vWF antigen levels. There were no patients with major
      bleeding events during the follow-up period. Four patients showed minor bleeding
      events (n = 1 vs. n = 3, elevated vs. normal patients, respectively). We found
      that the vWF antigen level was elevated and the TEG profiles were better in older
      ITP patients with longer disease statuses. Patients with ITP appeared to achieve
      a rebalance hemostasis through an elevation of their plasma vWF antigen levels
      and hemostatic changes that promote thrombosis. Measuring the vWF antigen levels
      and performing TEG analysis can help determine the treatment strategy in ITP
      patients.

PMID- 24433239
TI  - Maternal obesity and the developmental programming of hypertension: a role for
      leptin.
AB  - Mother-child cohort studies have established that both pre-pregnancy body mass
      index (BMI) and gestational weight gain are independently associated with cardio
      metabolic risk factors in young adult offspring, including systolic and diastolic
      blood pressure. Animal models in sheep and non-human primates provide further
      evidence for the influence of maternal obesity on offspring cardiovascular
      function, whilst recent studies in rodents suggest that perinatal exposure to the
      metabolic milieu of maternal obesity may permanently change the central
      regulatory pathways involved in blood pressure regulation. Leptin plays an
      important role in the central control of appetite, is also involved in activation
      of efferent sympathetic pathways to both thermogenic and non-thermogenic tissues,
      such as the kidney, and is therefore implicated in obesity-related hypertension.
      Leptin is also thought to have a neurotrophic role in the development of the
      hypothalamus, and altered neonatal leptin profiles secondary to maternal obesity
      are associated with permanently altered hypothalamic structure and function. In
      rodent studies, maternal obesity confers persistent sympathoexcitatory hyper
      responsiveness and hypertension acquired in the early stages of development.
      Experimental neonatal hyperleptinaemia in naive rat pups provides further
      evidence of heightened sympathetic tone and proof of principle that
      hyperleptinaemia during a critical window of hypothalamic development may
      directly lead to adulthood hypertension. Insight from these animal models raises
      the possibility that early-life exposure to leptin in humans may lead to early
      onset essential hypertension. Ongoing mother-child cohort and intervention
      studies in obese pregnant women provide a unique opportunity to address
      associations between maternal obesity and offspring cardiovascular function. The
      goal of the review is to highlight the potential importance of leptin in the
      developmental programming of hypertension in obese pregnancy. 

PMID- 24433240
TI  - Targeted delivery of silver nanoparticles and alisertib: in vitro and in vivo
      synergistic effect against glioblastoma.
AB  - AIM: Targeted biocompatible nanoplatforms presenting multiple therapeutic
      functions have great potential for the treatment of cancer. MATERIALS & METHODS:
      Multifunctional nanocomposites formed by polymeric nanoparticles (PNPs)
      containing two cytotoxic agents - the drug alisertib and silver nanoparticles -
      were synthesized. These PNPs have been conjugated with a chlorotoxin, an active
      targeting 36-amino acid-long peptide that specifically binds to MMP-2, a receptor
      overexpressed by brain cancer cells. RESULTS: The individual and synergistic
      activity of these two cytotoxic agents against glioblastoma multiforme was tested
      both in vitro and in vivo. The induced cytotoxicity in a human glioblastoma
      astrocytoma epithelial-like cell line (U87MG) was studied in vitro through a
      trypan blue exclusion test after 48 and 72 h of exposure. Subsequently, the PNPs'
      biodistribution in healthy animals and their effect on tumor reduction in tumor
      bearing mice were studied using PNPs radiolabeled with (99m)Tc. CONCLUSION: Tumor
      reduction was achieved in vivo when using silver/alisertib@PNPs-chlorotoxin.

PMID- 24433241
TI  - Response of cervicogenic headaches and occipital neuralgia to radiofrequency
      ablation of the C2 dorsal root ganglion and/or third occipital nerve.
AB  - OBJECTIVE: This article investigates the degree and duration of pain relief from
      cervicogenic headaches or occipital neuralgia following treatment with
      radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital
      nerves. It also addresses the procedure's complication rate and patient's
      willingness to repeat the procedure if severe symptoms recur. METHODS: This is a
      single-center retrospective observational study of 40 patients with refractory
      cervicogenic headaches and or occipital neuralgia. Patients were all referred by
      a headache specialty clinic for evaluation for radiofrequency ablation of the C2
      dorsal root ganglion and/or third occipital nerves. After treatment, patients
      were followed for a minimum of 6 months to a year. Patient demographics and the
      results of radiofrequency ablation were recorded on the same day, after 3-4 days,
      and at 6 months to 1 year following treatment. RESULTS: Thirty-five percent of
      patients reported 100% pain relief and 70% reported 80% or greater pain relief.
      The mean duration of improvement is 22.35 weeks. Complication rate was 12-13%.
      92.5% of patients reported they would undergo the procedure again if severe
      symptoms returned. CONCLUSIONS: Radiofrequency ablation of the C2 dorsal root
      ganglion and/or third occipital nerve can provide many months of greater than 50%
      pain relief in the vast majority of recipients with an expected length of symptom
      improvement of 5-6 months.

PMID- 24433243
TI  - Feeling bullied at the workplace.

PMID- 24433244
TI  - Can we "predict" long-term outcome for ambulatory transcutaneous electrical nerve
      stimulation in patients with chronic pain?
AB  - BACKGROUND: Evidence for effectiveness of transcutaneous electrical nerve
      stimulation (TENS) is still inconclusive. As heterogeneity of chronic pain
      patients might be an important factor for this lack of efficacy, identifying
      factors for a successful long-term outcome is of great importance. METHODS: A
      prospective study was performed to identify variables with potential predictive
      value for 2 outcome measures on long term (6 months); (1) continuation of TENS,
      and (2) a minimally clinical important pain reduction of >= 33%. At baseline, a
      set of risk factors including pain-related variables, psychological factors, and
      disability was measured. RESULTS: In a multiple logistic regression analysis,
      higher patient's expectations, neuropathic pain, no severe pain (< 80 mm visual
      analogue scale [VAS]) were independently related to long-term continuation of
      TENS. For the outcome "minimally clinical important pain reduction," the multiple
      logistic regression analysis indicated that no multisited pain (> 2 pain
      locations) and intermittent pain were positively and independently associated
      with a minimally clinical important pain reduction of >= 33%. CONCLUSION: The
      results showed that factors associated with a successful outcome in the long term
      are dependent on definition of successful outcome.

PMID- 24433245
TI  - Case of multiple apocrine poroma in a patient without receiving radiation or
      chemotherapy.

PMID- 24433246
TI  - Sources of individual differences in children's understanding of fractions.
AB  - Longitudinal associations of domain-general and numerical competencies with
      individual differences in children's understanding of fractions were
      investigated. Children (n = 163) were assessed at 6 years of age on domain
      general (nonverbal reasoning, language, attentive behavior, executive control,
      visual-spatial memory) and numerical (number knowledge) competencies; at 7 years
      on whole-number arithmetic computations and number line estimation; and at 10
      years on fraction concepts. Mediation analyses controlling for general
      mathematics ability and general academic ability revealed that numerical and
      mathematical competencies were direct predictors of fraction concepts, whereas
      domain-general competencies supported the acquisition of fraction concepts via
      whole-number arithmetic computations or number line estimation. Results indicate
      multiple pathways to fraction competence. 

PMID- 24433247
TI  - Cardiopulmonary bypass standby avoids fatality due to vascular laceration in
      laser-assisted lead extraction.
AB  - OBJECTIVES: Vascular laceration is a rare but potentially fatal complication with
      excimer laser-assisted pacemaker or implantable cardioverter-defibrillator lead
      extraction. We report our experience on management of vascular laceration during
      laser-assisted lead extraction. METHODS: We retrospectively reviewed 140
      consecutive patients undergoing laser-assisted lead extraction from May 2004 to
      March 2011. Clinical outcomes were compared in patients with and without
      intraoperative vascular laceration. Risk factors were identified by multivariate
      logistic regression. RESULTS: All cases were performed in the operating room with
      cardiopulmonary bypass standby. Complete lead removal was achieved in 118 (84.3%)
      patients. Potentially fatal complications occurred in five patients (3.6%) who
      had superior vena cava and/or innominate vein laceration. Lacerated veins were
      repaired under emergency sternotomy and cardiopulmonary bypass. The mean time
      from vascular laceration to establishment of cardiopulmonary bypass was 6.0 +/-
      3.6 minutes. All five patients survived without neurological sequelae. The rates
      of dual-coil leads (80.0% vs. 31.9%, p=0.025) and history of lead revision
      (100.0% vs. 40.0%, p=0.008) were significantly higher in the five patients who
      had major vascular laceration than those who did not. Logistic regression showed
      that dual-coil implantable cardioverter-defibrillator lead was an independent
      risk factor for vascular laceration (odds ratio 11.264, p=0.048). CONCLUSION:
      Cardiopulmonary bypass standby is helpful when performing laser-assisted lead
      extraction to treat potentially fatal vascular laceration. Dual-coil lead is an
      independent risk factor to predict intraoperative vascular laceration.

PMID- 24433248
TI  - Editorial. Health Expectations.

PMID- 24433250
TI  - Aspects of nursing with evidence-base when nursing frail older adults: a
      phenomenographic analysis of interviews with nurses in municipal care.
AB  - INTRODUCTION: In earlier research as well as in political discussion and
      documents, the topic of evidence has been highlighted as one of the most
      important concerns in nursing care. This study focuses on understanding what lies
      behind nurses' ways of acting regarding evidence-based nursing through an
      illumination of the way they perceive the phenomena. AIM: The aim was to identify
      and describe the different ways municipal care nurses perceive aspects of working
      with evidence when nursing frail older adults. METHODS: An explorative design
      with a phenomenographic approach based on interviews with nurses working with
      home-based care within the municipality was used in order to gain understanding
      of nurse's perceptions of the phenomena. RESULTS: Findings revealed that the
      nurses perceived a variety of aspects when working with evidence when nursing
      frail older people. Aspects with a spectra of different perceptions shown in the
      analysis were as follows: Evidence-based nursing as a desired intention/mission,
      lack of practical supporting structures to apply evidence, lack of confidence in
      own capacity to apply evidence and a belief that it will work anyway.
      CONCLUSIONS: Findings reveal that it is a challenge to implement research both on
      an individual as well as on an organisational level. Understanding the contextual
      perceptions of evidence by nurses can cast light on the barriers as well as the
      prerequisites of working with evidence while caring for frail older adults in
      municipal care.

PMID- 24433249
TI  - Cognitive behavioral therapy for insomnia in euthymic bipolar disorder: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Patients with bipolar disorder experience sleep disturbance, even in
      euthymic phases. Changes in sleep pattern are frequent signs of a new episode of
      (hypo)mania or depression. Cognitive behavioral therapy for insomnia (CBT-I) is
      an effective treatment for primary insomnia, but there are no published results
      on the effects of CBT-I in patients with bipolar disorder. In this randomized
      controlled trial, we wish to compare CBT-I and treatment as usual with treatment
      as usual alone to determine its effect in improving quality of sleep, stabilizing
      minor mood variations and preventing new mood episodes in euthymic patients with
      bipolar disorder and comorbid insomnia. METHODS: Patients with euthymic bipolar I
      or II disorder and insomnia, as verified by the Structured Clinical Interview for
      DSM Disorders (SCID-1) assessment, will be included. The patients enter a three
      week run-in phase in which they complete a sleep diary and a mood diary, are
      monitored for seven consecutive days with an actigraph and on two of these nights
      with polysomnography in addition before randomization to an eight-week treatment
      trial. Treatment as usual consists of pharmacological and supportive psychosocial
      treatment. In this trial, CBT-I will consist of sleep restriction,
      psychoeducation about sleep, stabilization of the circadian rhythm, and
      challenging and correcting sleep state misperception, in three to eight sessions.
      DISCUSSION: This trial could document a new treatment for insomnia in bipolar
      disorder with possible effects on sleep and on stability of mood. In addition,
      more precise information can be obtained about the character of sleep disturbance
      in bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01704352.

PMID- 24433251
TI  - Personal cancer knowledge and information seeking through PRISM: the planned risk
      information seeking model.
AB  - This study retested PRISM, a model of risk information seeking, and found that it
      is applicable to the context of cancer risk communication. The study, which used
      an online sample of 928 U.S. adults, also tested the effect of additional
      variables on that model and found that the original model better fit the data.
      Among the strongest predictors of cancer information seeking were seeking-related
      subjective norms, attitude toward seeking, perceived knowledge insufficiency, and
      affective risk response. Furthermore, risk perception was a strong predictor of
      an affective risk response. The authors suggest that, given the robustness across
      studies, the path between seeking-related subjective norms and seeking intention
      is ready to be implemented in communication practice. 

PMID- 24433252
TI  - Eliciting perceptions of satisfaction with services and supports from persons
      with intellectual disability and developmental disabilities: a review of the
      literature.
AB  - BACKGROUND: Assessing the perceptions of individuals with intellectual disability
      (ID) and developmental disabilities (DD) is an essential part of evaluating and
      planning services and an important component of respect for self-direction and
      autonomy. It can be difficult, however, to assess satisfaction in such a way that
      individuals with disabilities' actual perceptions of satisfaction are accurately
      represented because of intellectual and communication difficulties they may have,
      the restricted range and nature of service systems, and the limitations of
      strategies used by some researchers. METHOD: The purpose of this literature
      review was to systematically examine research studies designed to solicit
      personal satisfaction information from individuals with ID and DD. We reviewed 29
      studies that met inclusion criteria to determine (1) who were participants in the
      studies, (2) what processes researchers used to obtain opinions and perspectives
      of persons with ID and DD, and (3) how researchers ensured the credibility,
      accuracy and voluntariness of participants' responses. RESULTS: Findings revealed
      that most of the research participants had ID with higher IQs and limited needs
      for supports. Researchers utilised a variety of processes to elicit perceptions
      of satisfaction. Most studies employed individual interviews; researchers
      addressed comprehensibility of questions in a number of ways (e.g. use of
      visuals, adjusting wording of questions, providing clear examples). Few studies
      reported training interviewers or taking into account participants' primary
      language or cultural background. No studies reported educating participants about
      how to understand the satisfaction information data or how to use it in
      advocating for more appropriate supports. CONCLUSIONS: Assessing the satisfaction
      with supports and services of individuals with ID and DD is complex particularly
      for persons with extensive support needs. Continued research using varied
      conceptual frameworks and new technologies is needed. Also helpful will be
      teaching persons with disabilities about the assessment process and how to use
      its results.

PMID- 24433253
TI  - Antibiofilm activity of irrigating solutions associated with cetrimide. Confocal
      laser scanning microscopy.
AB  - AIM: To evaluate the antibiofilm activity of sodium hypochlorite (NaOCl) and
      chlorhexidine (CHX) solutions associated with cetrimide (CTR), and QMiX using
      confocal laser scanning microscopy. METHODOLOGY: Enterococcus faecalis (ATCC-
      29212) biofilms were induced on bovine dentine blocks for 14 days. The dentine
      blocks containing biofilm were immersed for 1 min in the following solutions:
      2.5% NaOCl; 2.5% NaOCl + 0.2% CTR; 2% CHX; 2% CHX + 0.2% CTR; 0.2% CTR; QMiX.
      After contact with the solutions, the dentine blocks were stained with
      Live/Dead((r)) BacLight for analysis of the remaining biofilm using confocal
      laser scanning microscope. Images were evaluated using the BioImage_L software to
      determine the total biovolume (MUm(3) ), the green biovolume (live cells) (MUm(3)
      ) and the percentage of substrate coverage (%). The data were subjected to
      nonparametric statistical test using Kruskal-Wallis and Dunn's tests at 5%
      significance level. RESULTS: After exposure to irrigants, the total biovolume
      observed for CHX, CHX+CTR, CTR, QMiX was similar to distilled water (P > 0.05).
      NaOCl and NaOCl+CTR had the lowest total and green biovolume. The CTR and QMiX
      had intermediate green biovolume, with greater antibacterial activity than CHX
      and CHX+CTR (P < 0.05). The NaOCl and NaOCl+CTR solutions were associated with
      microorganism removal and substrate cleaning ability. CONCLUSIONS: NaOCl and
      NaOCl+CTR solutions were effective on microorganism viability and were able to
      eliminate biofilm. The addition of cetrimide did not influence antibacterial
      activity.

PMID- 24433254
TI  - Input-output characteristics of soleus homonymous Ia afferents and corticospinal
      pathways during upright standing differ between young and elderly adults.
AB  - AIM: This study investigated the effects of ageing on the excitability of soleus
      homonymous Ia afferents and corticospinal pathways during bipedal upright
      standing. METHODS: The input-output relations for the Hoffmann (H) reflex and
      motor-evoked potential (MEP) were computed for the soleus in response to
      electrical nerve stimulation and transcranial magnetic stimulation, respectively,
      in young (n = 16) and elderly (n = 16) adults. In subsets of subjects, the input
      output relations were compared between normal and supported upright standing, and
      corticomotoneuronal excitability was assessed during upright standing with an H
      reflex conditioning method. For the H-reflex and MEP threshold, maximal amplitude
      (Hmax , MEPmax ) and the slope of the input-output relation (Hslope , MEPslope )
      were measured and normalized to the corresponding M-wave value. RESULTS: In
      normal standing, the Hmax /Mmax [mean (SD); young: 48.3 (14.2)%; elderly: 17.3
      (6.4)%] and Hslope /Mslope were significantly (P < 0.05) lower in elderly than in
      young adults, whereas the MEPmax /Mmax [young: 13.6 (7.5)%; elderly: 24.5
      (12.8)%] and MEPslope /Mslope were greater in elderly adults (P < 0.05). The
      Hslope /Mslope and MEPslope /Mslope decreased and increased, respectively, from
      supported to normal standing for both age groups but more so in elderly adults.
      Furthermore, the conditioned H reflex was greater (P < 0.05) in elderly [175.1
      (34.3)%] than in young adults [141.8 (29.8)%] during normal standing. CONCLUSION:
      This is the first study that clearly indicates lower efficacy of Ia afferents to
      discharge spinal motor neurones accompanied by greater corticospinal excitability
      in elderly adults, suggesting an increased contribution of the descending drive
      in controlling soleus activity during upright standing with ageing.

PMID- 24433255
TI  - Human platelet gel supernatant inactivates opportunistic wound pathogens on skin.
AB  - Activation of human platelets produces a gel-like substance referred to as
      platelet rich plasma or platelet gel. Platelet gel is used clinically to promote
      wound healing; it also exhibits antimicrobial properties that may aid in the
      healing of infected wounds. The purpose of this study was to quantify the
      efficacy of human platelet gel against the opportunistic bacterial wound
      pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus
      aureus on skin. These opportunistic pathogens may exhibit extensive antibiotic
      resistance, necessitating the development of alternative treatment options. The
      antimicrobial efficacy of platelet gel supernatants was quantified using an in
      vitro broth dilution assay, an ex vivo inoculated skin assay, and in an in vivo
      skin decontamination assay. Human platelet gel supernatants were highly
      bactericidal against A. baumannii and moderately but significantly bactericidal
      against S. aureus in vitro and in the ex vivo skin model. P. aeruginosa was not
      inactivated in vitro; a low but significant inactivation level was observed ex
      vivo. These supernatants were quite effective at inactivating a model organism on
      skin in vivo. These results suggest application of platelet gel has potential
      clinical applicability, not only in the acceleration of wound healing, but also
      against relevant bacteria causing wound infections.

PMID- 24433256
TI  - Genome-wide transcriptome study in wheat identified candidate genes related to
      processing quality, majority of them showing interaction (quality x development)
      and having temporal and spatial distributions.
AB  - BACKGROUND: The cultivated bread wheat (Triticum aestivum L.) possesses unique
      flour quality, which can be processed into many end-use food products such as
      bread, pasta, chapatti (unleavened flat bread), biscuit, etc. The present wheat
      varieties require improvement in processing quality to meet the increasing demand
      of better quality food products. However, processing quality is very complex and
      controlled by many genes, which have not been completely explored. To identify
      the candidate genes whose expressions changed due to variation in processing
      quality and interaction (quality x development), genome-wide transcriptome
      studies were performed in two sets of diverse Indian wheat varieties differing
      for chapatti quality. It is also important to understand the temporal and spatial
      distributions of their expressions for designing tissue and growth specific
      functional genomics experiments. RESULTS: Gene-specific two-way ANOVA analysis of
      expression of about 55 K transcripts in two diverse sets of Indian wheat
      varieties for chapatti quality at three seed developmental stages identified 236
      differentially expressed probe sets (10-fold). Out of 236, 110 probe sets were
      identified for chapatti quality. Many processing quality related key genes such
      as glutenin and gliadins, puroindolines, grain softness protein, alpha and beta
      amylases, proteases, were identified, and many other candidate genes related to
      cellular and molecular functions were also identified. The ANOVA analysis
      revealed that the expression of 56 of 110 probe sets was involved in interaction
      (quality x development). Majority of the probe sets showed differential
      expression at early stage of seed development i.e. temporal expression. Meta
      analysis revealed that the majority of the genes expressed in one or a few growth
      stages indicating spatial distribution of their expressions. The differential
      expressions of a few candidate genes such as pre-alpha/beta-gliadin and gamma
      gliadin were validated by RT-PCR. Therefore, this study identified several
      quality related key genes including many other genes, their interactions (quality
      x development) and temporal and spatial distributions. CONCLUSIONS: The candidate
      genes identified for processing quality and information on temporal and spatial
      distributions of their expressions would be useful for designing wheat
      improvement programs for processing quality either by changing their expression
      or development of single nucleotide polymorphisms (SNPs) markers.

PMID- 24433257
TI  - Excess risk of chronic physical conditions associated with depression and
      anxiety.
AB  - BACKGROUND: Depression and anxiety have been reported to be associated with
      chronic physical conditions. We examined the excess risk of chronic physical
      conditions associated with depression and/or anxiety within a multivariate
      framework controlling for demographic and modifiable lifestyle risk factors.
      METHODS: We used a retrospective cross-sectional study design. Study participants
      were adults aged 22-64 years from 2007 and 2009 Medical Expenditure Panel Survey.
      We defined presence of depression-anxiety based on self-reported depression and
      anxiety and classified adults into 4 groups: 1) depression only; 2) anxiety only;
      3) comorbid depression and anxiety 4) no depression and no anxiety. We included
      presence/absence of arthritis, asthma, chronic obstructive pulmonary disorder,
      diabetes, heart disease, hypertension, and osteoporosis as dependent variables.
      Complementary log-log regressions were used to examine the excess risk associated
      with depression and/or anxiety for chronic physical conditions using a
      multivariate framework that controlled for demographic (gender, age,
      race/ethnicity) and modifiable lifestyle (obesity, lack of physical activity,
      smoking) risk factors. Bonferroni correction for multiple comparisons was applied
      and p <=0.007 was considered statistically significant. RESULTS: Overall, 7% had
      only depression, 5.2% had only anxiety and 2.5% had comorbid depression and
      anxiety. Results from multivariable regressions indicated that compared to
      individuals with no depression and no anxiety, individuals with comorbid
      depression and anxiety, with depression only and with anxiety only, all had
      higher risk of all the chronic physical conditions. ARRs for comorbid depression
      and anxiety ranged from 2.47 (95% CI: 1.47, 4.15; P = 0.0007) for osteoporosis to
      1.64 (95% CI: 1.33, 2.04; P < 0.0001) for diabetes. Presence of depression only
      was also found to be significantly associated with all chronic conditions except
      for osteoporosis. Individuals with anxiety only were found to have a higher risk
      for arthritis, COPD, heart disease and hypertension. CONCLUSION: Presence of
      depression and/or anxiety conferred an independent risk for having chronic
      physical conditions after adjusting for demographic and modifiable lifestyle risk
      factors.

PMID- 24433258
TI  - Are social security policies for Chinese landless farmers really effective on
      health in the process of Chinese rapid urbanization? A study on the effect of
      social security policies for Chinese landless farmers on their health-related
      quality of life.
AB  - BACKGROUND: The continuing urbanization in China has resulted in a loss of land
      and rights among farmers. The social security of landless farmers has attracted
      considerable research attention. However, only few studies measure the health
      related quality of life (HRQOL) of landless farmers by employing scientific
      standardized scales. By using five-dimensional European quality of life (EQ-5D)
      scales, this study measures the HRQOL of landless farmers from a new perspective
      and examines how the social security policies affect their HRQOL. METHODS: This
      study is based on a 2013 household survey that has been conducted among 1,500
      landless famers who are residing in six resettlement areas in three cities within
      the Yangtze River Delta region, namely, Nanjing, Hangzhou, and Yangzhou. This
      study adopts EQ-5D scales to measure the HRQOL of these farmers. More than 50% of
      the respondents are in poor or non-serious health conditions, and over 50% are
      not satisfied with their current social security policies. The health conditions
      and social security policies are analyzed by multinomial regression analysis and
      the relationship between these two factors are analyzed via structural equation
      modeling (SEM). RESULTS: First, the descriptive statistical analysis shows that
      more than 50% of the respondents are in poor or non-serious health conditions,
      and that the largest proportion of these farmers are suffering from anxiety or
      depression, which is the most serious of the five dimensions. Second, multinomial
      regression analysis shows that the satisfaction of landless farmers with their
      social security policies improves their living conditions, particularly in their
      capacity for self-care, in their ability to perform daily activities, and in the
      reduction of pain, anxiety, and depression. Third, SEM model analysis shows that
      the satisfaction of landless farmers with their social security policies
      positively influences their HRQOL. Among the five dimensions of EQ-5D, daily
      activities produce the greatest influence on the HRQOL of landless farmers. As
      regards social security policies, the land acquisition compensation policy and
      the employment security policy produce the greatest and weakest influences on the
      HRQOL of landless farmers, respectively. CONCLUSIONS: The rapid urbanization in
      China has deprived many farmers of their lands and of the benefits of
      urbanization. These farmers are often in a disadvantaged position in the land
      acquisition process. Statistic analysis in this paper shows that the satisfaction
      of landless farmers with their social security policies positively influences
      their HRQOL. The implementation and improvement of social security policies is
      very important for the long-term and sustainable development of these landless
      farmers.

PMID- 24433259
TI  - Is intermittent androgen-deprivation therapy beneficial for patients with
      advanced prostate cancer?
AB  - Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate
      cancer has been evaluated in several studies, in an attempt to delay the
      development of castration resistance and reduce side-effects associated with ADT.
      However it is still not clear whether survival is adversely affected in patients
      treated with IADT. In this review, we explore the available data in an attempt to
      identify the most suitable candidate patients for IADT, and discuss factors that
      may inform appropriate patient stratification. ADT is first-line treatment for
      advanced/metastatic prostate cancer and is also recommended for use with
      definitive radiotherapy for high-risk localised prostate cancer. The changes in
      hormone levels induced by ADT can lead to short- and long-term side-effects
      which, although treatable in most cases, can significantly reduce the
      tolerability of ADT treatment. IADT has been investigated in several phase II and
      phase III studies in patients with locally advanced or metastatic prostate
      cancer, in an attempt to delay time to tumour progression and reduce the side
      effect burden of ADT. In selected patient groups IADT is no less effective than
      continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a
      degree, their impact on patient health-related quality of life (HRQL). Further
      comparative study is required, particularly in relation to HRQL and long-term
      complications associated with ADT. 

PMID- 24433260
TI  - The development of children's prelife reasoning: evidence from two cultures.
AB  - Two studies investigated children's reasoning about their mental and bodily
      states during the time prior to biological conception-"prelife." By exploring
      prelife beliefs in 5- to 12-year-olds (N = 283) from two distinct cultures (urban
      Ecuadorians, rural indigenous Shuar), the studies aimed to uncover children's
      untutored intuitions about the essential features of persons. Results showed that
      with age, children judged fewer mental and bodily states to be functional during
      prelife. However, children from both cultures continued to privilege the
      functionality of certain mental states (i.e., emotions, desires) relative to
      bodily states (i.e., biological, psychobiological, perceptual states). Results
      converge with afterlife research and suggest that there is an unlearned cognitive
      tendency to view emotions and desires as the eternal core of personhood. 

PMID- 24433261
TI  - Long-term outcomes of percutaneous radiofrequency thermocoagulation of gasserian
      ganglion for 2nd- and multiple-division trigeminal neuralgia.
AB  - OBJECTIVES: The objective of this study was to examine the long-term outcome of
      percutaneous radiofrequency thermocoagulation (PRT) of the Gasserian ganglion for
      the 2nd division and multiple division trigeminal neuralgia (TN), compared to the
      isolated 3rd division TN. METHODS: One hundred and forty-eight procedures
      performed in 89 patients with typical TN between April 2004 and September 2011 in
      a single pain center were retrospectively analyzed. Baseline characteristics of
      these patients, immediate outcome, duration pain-free, and complications were
      obtained from their medical records and questionnaires sent in June 2012.
      Duration pain-free was assessed by Kaplan-Meier analysis. RESULTS: Of the 148 PRT
      of the Gasserian ganglion, 37 procedures were performed for isolated 2nd-division
      TN (V2 TN), 67 procedures were for both 2nd- and 3rd-division TN (V2 + V3 TN),
      and 38 procedures were for isolated 3rd-division TN (V3 TN). The remaining 6
      procedures were performed for V1 + V2 TN and V1 + V2 + V3 TN. Immediate success
      rates of PRT for V2 TN, V2 + V3 TN, and V3 TN were 100%, 86.6%, and 100%,
      respectively, whereas the durations pain-free for V2 TN and V2 + V3 TN were
      significantly shorter than that for V3 TN (9, 12, and 36 months, respectively: P
      = 0.012). CONCLUSION: For 2nd-division TN and multiple-division TN, less long
      term pain relief after PRT of the Gasserian ganglion can be expected compared
      with that for isolated trigeminal 3rd-division neuralgia, even if immediate pain
      relief is achieved.

PMID- 24433262
TI  - From stillness to motion: 80 years after the first description of Taenia solium
      oncosphere hatching.
AB  - BACKGROUND: Human neurocysticercosis (NCC) is a considered public health problem
      in many underdeveloped and developing countries. Because of the enormous increase
      in international tourism and migration, NCC nowadays is also found in some
      developed countries. Our group was the first to demonstrate that tapeworm
      carriers in the household are the main risk factor for acquiring cysticercosis in
      humans and pigs, since the disease results from the ingestion of microscopic
      tapeworm eggs. FINDINGS: We had the opportunity to film the liberation of the
      embryo from the oncospheral membrane after the hatching of the egg, which is the
      activation process required for intestinal wall invasion by the onchosphere.
      Yoshino (J Formosa Med Ass 32:139-142, 1933) described with great detail in
      diagrams and photographs this process eighty years ago after he infected himself
      with three living cysticerci in order to study the life cycle of Taenia solium.
      Other authors further described this process. Nevertheless it has never been
      filmed before. The purpose of this paper is to shift from stillness to motion
      since we can now show for the first time a movie of an activated oncosphere and
      its release from the oncospheral membrane. CONCLUSION: Oncospheral activation is
      the requisite for T. solium embryos to invade the intestinal mucosa and develop
      into cysticerci. This process has been amply described but here it is shown for
      the first time in motion; thus it may be of interest for readers of the journal
      and useful for educational purposes towards the control of NCC.

PMID- 24433263
TI  - Unusually extensive disseminated herpes zoster with multiple ulcer formation in a
      methotrexate-treated rheumatoid arthritis patient.

PMID- 24433264
TI  - Intracutaneous suture versus transcutaneous skin stapling for closure of midline
      or horizontal skin incision in elective abdominal surgery and their outcome on
      superficial surgical site infections--INTRANS: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Surgical site infections are the third most frequent type of
      nosocomial infections. Evidence-based recommendations have been given regarding
      preoperative hospitalization, hygiene and air-conditioning, patient conditions,
      and wound dressing. However, no general recommendations concerning wound closure
      exist. Systematic reviews and meta-analyses suppose a benefit of intracutaneous
      suture compared to skin staples in orthopedic and obstetric surgery. Literature
      data for skin closure in elective abdominal surgery are still deficient.
      METHODS/DESIGN: Patients scheduled for any elective abdominal surgery requiring
      midline or horizontal laparotomy are potentially eligible for the trial. Trial
      specific exclusion criteria are date of admission exceeding four days prior to
      surgery, antibiotic treatment within the past 14 days, any previous midline or
      horizontal laparotomy in case the procedure requires the same skin incision as
      before, neurophysiological deficits or severe psychiatric or neurologic diseases
      that do not allow an informed consent or compliance, and participation in any
      other interventional trial with interference of intervention and outcome. The
      trial is created for process innovation within standardized surgical procedures.
      It is designed as a prospective randomized controlled single center trial in a
      parallel design including an active comparator and an intervention group. The
      intervention addresses the closure of skin after the main surgical procedure:
      intracutaneous suture in the intervention group and transcutaneous skin stapling
      in the control group. The rate of superficial surgical site infections is defined
      as the primary endpoint. Secondary endpoints are time for skin closure,
      satisfaction with the cosmetic outcome 30 days after surgery, prolongation of
      hospital stay, and duration of sick-leave due to surgical site infections. The
      primary efficacy analysis follows the intention-to-treat principle. A chi2 test
      will be applied. DISCUSSION: The trial is expected to balance the shortcomings of
      the current evidence. It will help to define the gold standard for wound closure
      in elective abdominal surgery. Patients' safety and quality of life are assumed
      to be enhanced. Therapy costs are likely to be reduced and health care optimized.
      TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00004542.

PMID- 24433265
TI  - The use of epidural analgesia for intrapartum pain relief in publicly funded
      healthcare.
AB  - BACKGROUND: Epidural analgesia is the most effective way to relieve pain during
      birth. In a population-based case-control study, we evaluated whether
      socioeconomic status (SES) affects the use of epidural analgesia for intrapartum
      pain relief in publicly funded health care. METHODS: Data gathered from the
      Finnish Medical Birth Register included all singleton births (n = 521,179) in
      2000-2010. The likelihood of receiving epidural analgesia according to vaginal
      birth order, socio-demographic factors and delivery characteristics was
      determined by using logistic regression analysis. RESULTS: Overall, 66.6% of
      women with first vaginal births and 22.4% of women with second or subsequent
      vaginal births had epidural analgesia. The use of epidural analgesia was
      associated with several factors, such as post-term pregnancy, gestational
      diabetes, maternal diabetes mellitus, single marital status, smoking, depression
      and fear of childbirth, induction, high birth weight and giving birth by vacuum
      extraction regardless of vaginal birth order. Epidural use did not vary
      substantially by SES in first vaginal births, but a minor difference was found in
      second or subsequent vaginal births. The prevalence of epidural analgesia was 3%
      [adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.93-1.00] and 13%
      (aOR 0.87, 95% CI 0.83-0.90) lower among lower white-collar workers and blue
      collar workers, respectively, compared with upper white-collar workers.
      CONCLUSIONS: In Finland, the use of epidural analgesia for intrapartum pain
      relief reflected clinical indications and did not substantially vary by SES
      regardless of vaginal birth order. This could be considered as an important
      indicator measuring health equality.

PMID- 24433266
TI  - The importance of synovitis diagnosis in osteoarthritis patients in the
      evaluation of mean platelet volume.

PMID- 24433267
TI  - Type A aortic dissection: a rare complication of central venous catheter
      placement.
AB  - Aortic injury during central venous catheter (CVC) insertion is an extremely rare
      complication. We report successful repair of an iatrogenic type A aortic
      dissection caused during mediport catheter insertion and discuss the prevention
      and management of aortic injury during CVC placement.

PMID- 24433268
TI  - When a smoking gun is not enough: unusual association in secondary headache.

PMID- 24433269
TI  - Evaluation of a wearable physiological status monitor during simulated fire
      fighting activities.
AB  - A physiological status monitor (PSM) has been embedded in a fire-resistant shirt.
      The purpose of this research study was to examine the ability of the PSM-shirt to
      accurately detect heart rate (HR) and respiratory rate (RR) when worn under
      structural fire fighting personal protective equipment (PPE) during the
      performance of various activities relevant to fire fighting. Eleven healthy,
      college-aged men completed three activities (walking, searching/crawling, and
      ascending/descending stairs) that are routinely performed during fire fighting
      operations while wearing the PSM-shirt under structural fire fighting PPE. Heart
      rate and RR recorded by the PSM-shirt were compared to criterion values measured
      concurrently with an ECG and portable metabolic measurement system, respectively.
      For all activities combined (overall) and for each activity, small differences
      were found between the PSM-shirt and ECG (mean difference [95% CI]: overall: -0.4
      beats/min [-0.8, -0.1]; treadmill: -0.4 beats/min [-0.7, -0.1]; search: -1.7
      beats/min [-3.1, -.04]; stairs: 0.4 beats/min [0.04, 0.7]). Standard error of the
      estimate was 3.5 beats/min for all tasks combined and 1.9, 5.9, and 1.9 beats/min
      for the treadmill walk, search, and stair ascent/descent, respectively.
      Correlations between the PSM-shirt and criterion heart rates were high (r = 0.95
      to r = 0.99). The mean difference between RR recorded by the PSM-shirt and
      criterion overall was 1.1 breaths/min (95% CI: -1.9 to -0.4). The standard error
      of the estimate for RR ranged from 4.2 breaths/min (treadmill) to 8.2 breaths/min
      (search), with an overall value of 6.2 breaths/min. These findings suggest that
      the PSM-shirt provides valid measures of HR and useful approximations of RR when
      worn during fire fighting duties.

PMID- 24433270
TI  - Topical cidofovir for plantar warts.
AB  - Plantar warts are a common reason for dermatological consultations and their
      treatment can occasionally be a challenge. Plantar warts are benign lesions
      produced by the human papillomavirus (HPV) that often fail to respond to habitual
      treatment. Cidofovir is a potent antiviral drug that acts competitively,
      inhibiting viral DNA polymerase. Our aim was to assess the efficacy and safety of
      cidofovir cream for the treatment of viral plantar warts. We undertook a
      retrospective observational study of patients with plantar warts who received
      treatment with topical cidofovir between July 2008 and July 2011 at the
      Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data about
      the rate of treatment response, the adverse effects, and recurrences, as well as
      the characteristics of the patient cohort, were recorded. We identified 35
      patients who had received some previous treatment. The usual concentration was 3%
      (in 33 of 35 cases), applied twice a day (in 31 of 35 cases). A greater or lesser
      response was noted in 28 cases. There were two recurrences. Topical cidofovir
      seems to be a useful alternative for the therapeutic management of recalcitrant
      plantar common warts that fail to respond to usual treatment. 

PMID- 24433271
TI  - Effect of three NiTi files on transportation of the apical foramen.
AB  - AIM: To compare landed and nonlanded rotary file overinstrumentation on
      transportation of the apical foramen in the curved canals of extracted teeth.
      METHODOLOGY: Severely curved molar root canals (n = 45) were distributed into
      three equal groups (n = 15) according to angle (mean 54 degrees ) and radius of
      curvature (mean 5 mm). Canals were overinstrumented 0.5 mm beyond the foramen to
      a size 35 master apical file using landed (ProFile ISO), nonlanded (ProFile
      Vortex) or nonlanded, reduced shape memory (Vortex Blue) files. Post
      instrumentation images of the apical foramen were compared with pre
      instrumentation control images for differences in area, circularity and ratio of
      Feret's diameters. Groups were compared using anova or Kruskal-Wallis tests with
      significance of P < 0.05. RESULTS: There were no differences between pre
      treatment groups in the parameters tested. All groups demonstrated alterations in
      the geometry of the apical foramen. There were no significant differences between
      ProFile ISO, ProFile Vortex or Vortex Blue in area, circularity and ratio of
      Feret's diameters. CONCLUSIONS: Landed, nonlanded and nonlanded reduced shape
      memory files all produced transportation of the apical foramen when
      overinstrumented by 0.5 mm in severely curved canals. There was no difference
      between these file systems with regard to the degree of this effect.

PMID- 24433273
TI  - Comparison between a new platelet count drop method PL-11, light transmission
      aggregometry, VerifyNow aspirin system and thromboelastography for monitoring
      short-term aspirin effects in healthy individuals.
AB  - Platelet function has been described by many laboratory assays, and PL-11 is a
      new point-of-care platelet function analyzer based on platelet count drop method,
      which counts platelet before and after the addition of agonists in the citrated
      whole blood samples. The present study sought to compare PL-11 with other three
      major more established assays, light transmission aggregometry (LTA), VerifyNowTM
      aspirin system and thromboelastography (TEG), for monitoring the short-term
      aspirin responses in healthy individuals. Ten healthy young men took 100 mg/d
      aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA,
      VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2
      hour, 1 day during the aspirin treatment and 1 day, 5 +/- 1 days, 8 +/- 1 days
      after the aspirin withdrawal. Moreover, 90 additional healthy subjects were
      recruited to establish a reference range for PL-11. Platelet function of healthy
      subjects decreased significantly 2 hours after 100 mg/d aspirin intake and began
      to recover during 4-6 days after the aspirin withdrawal. Correlations between
      methods were PL-11 vs. LTA (r = 0.614, p < 0.01); PL-11 vs. VerifyNow (r = 0.829,
      p < 0.01); PL-11 vs. TEG (r = 0.697, p < 0.001). There was no significant bias
      between PL-11 and LTA at baseline (bias = 1.94%, p = 0.804) using Bland-Altman
      analysis, while the data of PL-11 were significantly higher than LTA (bias =
      24.02%, p < 0.001) during the aspirin therapy. The reference range for PL-11 in
      healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low
      responsiveness was defined as LTA > 20%, the cut-off values for each method were,
      respectively: PL-11 > 50%, VerifyNow > 533 ARU, TEG > 60.2%. The results of
      different platelet function assays were uninterchangeable for monitoring aspirin
      response and correlations among them were also varied. Correlations among PL-11
      and other three major assays suggested the ability of PL-11 to assess the
      treatment effects of aspirin. But a large cohort study is needed to confirm the
      cut-off value of aspirin response detected by PL-11.

PMID- 24433275
TI  - Conversation with Charles P. O'Brien.

PMID- 24433274
TI  - Plasma protein profiling of Mild Cognitive Impairment and Alzheimer's disease
      using iTRAQ quantitative proteomics.
AB  - BACKGROUND: With the promise of disease modifying treatments, there is a need for
      more specific diagnosis and prognosis of Alzheimer's disease (AD) and mild
      cognitive impairment (MCI). Plasma biomarkers are likely to be utilised to
      increase diagnostic accuracy and specificity of AD and cognitive decline.
      METHODS: Isobaric tags (iTRAQ) and proteomic methods were used to identify
      potential plasma biomarkers of MCI and AD. Relative protein expression level
      changes were quantified in plasma of 411 cognitively normal subjects, 19 AD
      patients and 261 MCI patients. Plasma was pooled into 4 groups including normal
      control, AD, amnestic single and multiple domain MCI (aMCI), and nonamnestic
      single and multiple domain MCI (nMCI). Western-blotting was used to validate
      iTRAQ data. Integrated function and protein interactions were explored using WEB
      based bioinformatics tools (DAVID v6.7 and STRING v9.0). RESULTS: In at least two
      iTRAQ replicate experiments, 30 proteins were significantly dysregulated in MCI
      and AD plasma, relative to controls. These proteins included ApoA1, ApoB100,
      complement C3, C4b-binding protein, afamin, vitamin D-binding protein precursor,
      isoform 1 of Gelsolin actin regulator, Ig mMU chain C region (IGHM), histidine
      rich glycoprotein and fibrinogen beta and gamma chains. Western-blotting
      confirmed that afamin was decreased and IGHM was increased in MCI and AD groups.
      Bioinformatics results indicated that these dysregulated proteins represented a
      diversity of biological processes, including acute inflammatory response,
      cholesterol transport and blood coagulation. CONCLUSION: These findings
      demonstrate that expression level changes in multiple proteins are observed in
      MCI and AD plasma. Some of these, such as afamin and IGHM, may be candidate
      biomarkers for AD and the predementia condition of MCI.

PMID- 24433272
TI  - Sex differences in human fatigability: mechanisms and insight to physiological
      responses.
AB  - Sex-related differences in physiology and anatomy are responsible for profound
      differences in neuromuscular performance and fatigability between men and women.
      Women are usually less fatigable than men for similar intensity isometric
      fatiguing contractions. This sex difference in fatigability, however, is task
      specific because different neuromuscular sites will be stressed when the
      requirements of the task are altered, and the stress on these sites can differ
      for men and women. Task variables that can alter the sex difference in
      fatigability include the type, intensity and speed of contraction, the muscle
      group assessed and the environmental conditions. Physiological mechanisms that
      are responsible for sex-based differences in fatigability may include activation
      of the motor neurone pool from cortical and subcortical regions, synaptic inputs
      to the motor neurone pool via activation of metabolically sensitive small
      afferent fibres in the muscle, muscle perfusion and skeletal muscle metabolism
      and fibre type properties. Non-physiological factors such as the sex bias of
      studying more males than females in human and animal experiments can also mask a
      true understanding of the magnitude and mechanisms of sex-based differences in
      physiology and fatigability. Despite recent developments, there is a tremendous
      lack of understanding of sex differences in neuromuscular function and
      fatigability, the prevailing mechanisms and the functional consequences. This
      review emphasizes the need to understand sex-based differences in fatigability to
      shed light on the benefits and limitations that fatigability can exert for men
      and women during daily tasks, exercise performance, training and rehabilitation
      in both health and disease. 

PMID- 24433276
TI  - Physical activity and sedentary behavior among adolescents in rural South Africa:
      levels, patterns and correlates.
AB  - BACKGROUND: Physical inactivity is increasing among children and adolescents and
      may be contributing to the increasing prevalence of overweight and obesity. This
      study examines physical activity and sedentary behavior patterns, and explores
      associations with individual, maternal, household, and community factors amongst
      rural South African adolescents. METHODS: In 2009, 381 subjects, stratified by
      ages 11-12-years and 14-15-years, were randomly selected from 3511 children and
      adolescents who had participated in a growth survey two years previously. Weight
      and height were measured and self-reported Tanner pubertal stage was collected. A
      questionnaire quantifying frequency and duration of physical activity (PA)
      domains and sedentary time for the previous 12 months was administered. Moderate
      vigorous physical activity (MVPA mins/wk) was calculated for time spent in school
      and club sport. Socio-demographic and other related data were included from the
      Agincourt health and socio-demographic system (HDSS). The Agincourt HDSS was
      established in 1992 and collects prospective data on the community living in the
      Agincourt sub-district of Mpumalanga Province in rural north-east South Africa.
      RESULTS: Puberty, maternal education and socio-economic status (SES) contributed
      significantly to the mulitiple linear regression model for sedentary behavior (R2
      = 0.199; adjusted R2 = 0.139; p < 0.000), and sex, SES and maternal education
      contributed to the tobit regression model for school and club sport MVPA (p <
      0.000). MVPA, calculated from school and club sport, was higher in boys than
      girls (p < 0.001), and informal activity was lower (boys: p < 0.05 and girls: p <
      0.01) while sedentary time was higher (girls: p < 0.01) in the older than the
      younger groups. Ninety-two percent (92%) of the sample reported walking for
      transport. CONCLUSIONS: In this study of rural South African adolescent boys and
      girls, SES at the maternal, household and community level independently predicted
      time spent in sedentary behaviors, and school and club MVPA. This study provides
      local data that can be used to develop health promotion strategies specific to
      this community, and other similar communities in developing countries.

PMID- 24433277
TI  - Spatial and temporal expression patterns of auxin response transcription factors
      in the syncytium induced by the beet cyst nematode Heterodera schachtii in
      Arabidopsis.
AB  - Plant-parasitic cyst nematodes induce the formation of a multinucleated feeding
      site in the infected root, termed the syncytium. Recent studies point to key
      roles of the phytohormone auxin in the regulation of gene expression and
      establishment of the syncytium. Nevertheless, information about the
      spatiotemporal expression patterns of the transcription factors that mediate
      auxin transcriptional responses during syncytium formation is limited. Here, we
      provide a gene expression map of 22 auxin response factors (ARFs) during the
      initiation, formation and maintenance stages of the syncytium induced by the cyst
      nematode Heterodera schachtii in Arabidopsis. We observed distinct and
      overlapping expression patterns of ARFs throughout syncytium development phases.
      We identified a set of ARFs whose expression is predominantly located inside the
      developing syncytium, whereas others are expressed in the neighbouring cells,
      presumably to initiate specific transcriptional programmes required for their
      incorporation within the developing syncytium. Our analyses also point to a role
      of certain ARFs in determining the maximum size of the syncytium. In addition,
      several ARFs were found to be highly expressed in fully developed syncytia,
      suggesting a role in maintaining the functional phenotype of mature syncytia. The
      dynamic distribution and overlapping expression patterns of various ARFs seem to
      be essential characteristics of ARF activity during syncytium development. 

PMID- 24433278
TI  - Suicidal ideation in patients with fibromyalgia: a cross-sectional study.
AB  - Chronic pain, sleep disturbances, and depression, which are relevant symptoms of
      fibromyalgia syndrome, have been demonstrated to be associated with an increased
      likelihood of suicidal behaviors. Mortality from suicide has been shown to be
      greater among patients with fibromyalgia. This study aimed to assess the
      prevalence of suicidal ideation among a sample of patients with fibromyalgia and
      to evaluate its relationship with the clinical symptomatology of fibromyalgia.
      Baseline data from fibromyalgia patients willing to participate in different
      clinical studies were collected. Outcome measures included the Fibromyalgia
      Impact Questionnaire, the Beck Depression Inventory, the Pittsburgh Sleep Quality
      Index, the Brief Pain Inventory, and the SF-12 Health Survey. The scores for
      these scales were compared between patients with and without suicidal ideation.
      The presence of suicidal ideation was assessed using the answer provided to item
      9 of the Beck Depression Inventory. The results were adjusted by age, sex, total
      comorbidity, and time since diagnosis with multiple linear regression. The sample
      comprised 373 patients of whom one hundred and seventy-nine (48%) reported
      suicidal ideation: 148 (39.7%) reported passive suicidal ideation and 31 (8.3%)
      active suicidal ideation. Suicidal ideation was markedly associated with
      depression, anxiety, sleep quality, and global mental health, whereas only weak
      relationships were observed between suicidal ideation and both pain and general
      physical health. 

PMID- 24433280
TI  - Langerhans cell histiocytosis presenting as a nodule beneath the clitoral hood.

PMID- 24433279
TI  - Molecular detection of Dirofilaria immitis, Dirofilaria repens and Setaria tundra
      in mosquitoes from Germany.
AB  - BACKGROUND: As a result of globalization and climate change, Dirofilaria immitis
      and Dirofilaria repens, the causative agents of dirofilariosis in Europe,
      continue to spread from endemic areas in the Mediterranean to northern and
      northeastern regions of Europe where autochthonous cases of dirofilarial
      infections have increasingly been observed in dogs and humans. Whilst D. repens
      was recently reported from mosquitoes in putatively non-endemic areas, D. immitis
      has never been demonstrated in mosquitoes from Europe outside the Mediterranean.
      METHODS: From 2011 to 2013, mosquitoes collected within the framework of a German
      national mosquito monitoring programme were screened for filarial nematodes using
      a newly designed filarioid-specific real-time PCR assay. Positive samples were
      further processed by conventional PCR amplification of the cytochrome c oxidase
      subunit I (COI) gene, amplicons were sequenced and sequences blasted against
      GenBank. RESULTS: Approximately 17,000 female mosquitoes were subjected to
      filarial screening. Out of 955 pools examined, nine tested positive for filariae.
      Two of the COI sequences indicated D. immitis, one D. repens and four Setaria
      tundra. Two sequences could not be assigned to a known species due to a lack of
      similar GenBank entries. Whilst D. immitis and the unknown parasites were
      detected in Culex pipiens/torrentium, D. repens was found in a single Anopheles
      daciae and all S. tundra were demonstrated in Aedes vexans. All positive
      mosquitoes were collected between mid-June and early September. CONCLUSION: The
      finding of dirofilariae in German mosquitoes implies the possibility of a local
      natural transmission cycle. While the routes of introduction to Germany and the
      origin of the filariae cannot be determined retrospectively, potential culicid
      vectors and reservoir hosts must prospectively be identified and awareness among
      physicians, veterinarians and public health personnel be created. The health
      impact of S. tundra on the indigenous cervid fauna needs further investigation.

PMID- 24433281
TI  - Leucocyte complement receptor 1 (CR1/CD35) transcript and its correlation with
      the clinical disease activity in rheumatoid arthritis patients.
AB  - In view of the exaggerated complement activation in rheumatoid arthritis (RA) and
      significance of complement receptor 1 (CR1/CD35) as a complement regulatory
      protein (CRP), we aimed to determine the leucocyte-complement receptor 1 (L-CR1)
      transcript levels and the relationship of this protein with the clinical disease
      activity of RA patients. Sixty-six controls and 45 RA patients were enrolled. L
      CR1 transcript levels were correlated with the levels of circulating immune
      complexes (CIC), C3, C4 and C3d in controls and patients and with disease
      activity score 28 (DAS28) in patients only. CIC levels were determined by
      polyethylene glycol (PEG) precipitation, C3 and C4 levels by nephlometry and C3d
      levels by enzyme-linked immunosorbent assay (ELISA). Eleven patients were
      recruited for follow-up of L-CR1 and DAS28 levels at weeks 0, 12 and 24.
      Appropriate statistical methods were used for the data analysis. L-CR1 (P < 0.01)
      transcript levels were decreased in patients compared to controls. L-CR1 levels
      correlated negatively with DAS28, CIC and C3d. DAS28 correlated positively with
      levels of CIC, C3 and C3d. Levels of CIC correlated positively with C3 and C3d.
      Levels of C3 correlated positively with C3d in patients and with C4 in both
      controls and patients. Levels of L-CR1 increased with decline in DAS28 scores in
      follow-up patients. Observations were statistically significant. Lower levels of
      L-CR1 transcript in patients compared to controls, their correlations with the
      levels of CIC, C3d and DAS28 at different time-points in RA patients suggest CR1
      as a potential disease marker for RA. 

PMID- 24433283
TI  - Ultrasonographic fetal soft markers in a low-risk population: prevalence,
      association with trisomies and invasive tests.
AB  - OBJECTIVE: To investigate the prevalence of soft markers identified at second
      trimester ultrasound in a low-risk population and the association of these
      markers with trisomies and invasive testing. DESIGN: Prospective observational
      study. SETTING: Swedish University Hospital. POPULATION: All women with fetuses
      examined by ultrasound at 15(+0) -22(+0)  weeks gestation between July 2008 and
      March 2011. METHODS: Cases with soft markers were compared with non-cases with
      regard to trisomies and invasive testing. MAIN OUTCOME MEASURES: Prevalence of
      soft markers, likelihood ratio for trisomies and risk ratio for invasive tests
      after detection of soft markers. RESULTS: Second trimester ultrasound was
      performed on 10 710 fetuses. Markers were detected in 5.9% of fetuses. 5.1% were
      isolated, 0.7% were multiple and 0.1% were combined with an anomaly. Presence of
      markers showed a positive likelihood ratio for Down syndrome, but the association
      (likelihood ratio = 7.1) was only statistically significant for the combined
      category of any marker (isolated, multiple or combined with anomaly). The risk
      ratio for invasive testing after the second trimester ultrasound was 24.0 in
      pregnancies with isolated soft markers compared with those without markers.
      CONCLUSION: In a low-risk population, soft markers were found in 5.9% of fetuses
      at second trimester ultrasound. The likelihood ratio for Down syndrome was
      significant only for any marker (isolated, multiple or combined with anomaly).
      The presence of soft markers increased the incidence of invasive procedures
      substantially. Soft markers should be noted when information on second trimester
      ultrasound is formulated, and all units performing fetal ultrasound examinations
      should have established routines concerning information management when soft
      markers are identified.

PMID- 24433282
TI  - Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse
      methylome.
AB  - BACKGROUND: Environmental factors during perinatal development may influence
      developmental plasticity and disease susceptibility via alterations to the
      epigenome. Developmental exposure to the endocrine active compound, bisphenol A
      (BPA), has previously been associated with altered methylation at candidate gene
      loci. Here, we undertake the first genome-wide characterization of DNA
      methylation profiles in the liver of murine offspring exposed perinatally to
      multiple doses of BPA through the maternal diet. RESULTS: Using a tiered focusing
      approach, our strategy proceeds from unbiased broad DNA methylation analysis
      using methylation-based next generation sequencing technology to in-depth
      quantitative site-specific CpG methylation determination using the Sequenom
      EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in
      offspring maternally exposed to BPA during gestation and lactation to doses
      ranging from 0 BPA/kg (Ctr), 50 MUg BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N = 4
      per group). Genome-wide analyses indicate non-monotonic effects of DNA
      methylation patterns following perinatal exposure to BPA, corroborating previous
      studies using multiple doses of BPA with non-monotonic outcomes. We observed
      enrichment of regions of altered methylation (RAMs) within CpG island (CGI)
      shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter
      regions identified several hundred novel BPA-associated methylation events, and
      methylation alterations in the Myh7b and Slc22a12 gene promoters were validated.
      Using the Comparative Toxicogenomics Database, a number of candidate genes that
      have previously been associated with BPA-related gene expression changes were
      identified, and gene set enrichment testing identified epigenetically
      dysregulated pathways involved in metabolism and stimulus response. CONCLUSIONS:
      In this study, non-monotonic dose dependent alterations in DNA methylation among
      BPA-exposed mouse liver samples and their relevant pathways were identified and
      validated. The comprehensive methylome map presented here provides candidate loci
      underlying the role of early BPA exposure and later in life health and disease
      status.

PMID- 24433286
TI  - Nano-sized aerosol classification, collection and analysis--method development
      using dental composite materials.
AB  - This article presents a methodical approach for generating, collecting, and
      analyzing nano-size (1-100 nm) aerosol from abraded dental composite materials.
      Existing aerosol sampling instruments were combined with a custom-made sampling
      chamber to create and sample a fresh, steady-state aerosol size distribution
      before significant Brownian coagulation. Morphological, size, and compositional
      information was obtained by Transmission Electron Microscopy (TEM). To create
      samples sizes suitable for TEM analysis, aerosol concentrations in the test
      chamber had to be much higher than one would typically expect in a dental office,
      and therefore, these results do not represent patient or dental personnel
      exposures. Results show that nano-size aerosol was produced by the dental drill
      alone, with and without cooling water drip, prior to abrasion of dental
      composite. During abrasion, aerosol generation seemed independent of the percent
      filler load of the restorative material and the operator who generated the test
      aerosol. TEM investigation showed that "chunks" of filler and resin were
      generated in the nano-size range; however, free nano-size filler particles were
      not observed. The majority of observed particles consisted of oil droplets, ash,
      and graphitic structures. 

PMID- 24433284
TI  - Selective intestinal cobalamin malabsorption with proteinuria (Imerslund-Grasbeck
      syndrome) in juvenile Beagles.
AB  - BACKGROUND: Selective intestinal cobalamin malabsorption with mild proteinuria
      (Imerslund-Grasbeck syndrome; I-GS), is an autosomal recessive disorder of dogs
      caused by mutations in AMN or CUBN that disrupt cubam function and which can
      present as a medical emergency. OBJECTIVES: To describe the clinical, metabolic,
      and genetic bases of I-GS in Beagles. ANIMALS: Four cobalamin-deficient and 43
      clinically normal Beagles and 5 dogs of other breeds. METHODS: Clinical
      description and candidate gene genetic study. Urinary organic acid and protein
      excretion were determined by gas-chromatography and SDS-PAGE, respectively. Renal
      cubilin protein expression was assessed on immunoblots. Mutation discovery was
      carried out by PCR amplification and DNA sequencing of exons with flanking splice
      sites and cDNA of CUBN and AMN. Genotyping was performed by restriction enzyme
      digestion of PCR amplicons. RESULTS: Juvenile-affected Beagles exhibited failure
      to thrive, dyshematopoiesis with neutropenia, serum cobalamin deficiency,
      methylmalonic aciduria, hyperammonemia, and proteinuria. Affected dogs' kidneys
      lacked detectable cubilin protein. All affected dogs were homozygous for a single
      base deletion in CUBN exon 8 (CUBN c.786delC), predicting a translational
      frameshift, and the 2 parents tested were heterozygous. CONCLUSIONS: The CUBN
      mutation in juvenile I-GS Beagles causes a more severe cobalamin malabsorption
      than in Border Collies with a different CUBN defect, but is similar to I-GS
      caused by AMN mutations in Giant Schnauzers and Australian Shepherds. Awareness
      of the disorder and breed predispositions to I-GS is crucial to precisely
      diagnose and promptly treat hereditary cobalamin malabsorption and to prevent
      disease in those dogs at risk in future generations.

PMID- 24433285
TI  - The effect of febuxostat to prevent a further reduction in renal function of
      patients with hyperuricemia who have never had gout and are complicated by
      chronic kidney disease stage 3: study protocol for a multicenter randomized
      controlled study.
AB  - BACKGROUND: Hyperuricemia is a risk factor for the onset of chronic kidney
      disease (CKD) and is significantly associated with the progression of CKD.
      However, there is no sufficient evidence by interventional research supporting a
      cause-effect relationship. Hyperuricemic patients without gouty arthritis, whose
      serum urate (SUA) concentration is >=8.0 mg/dL and who have a complication, are
      treated by pharmacotherapy in addition to lifestyle guidance. Nevertheless, there
      is no evidence that rationalizes pharmacotherapy for patients with hyperuricemia
      who have no complication and whose SUA concentration is below 9.0 mg/dL.
      METHODS/DESIGN: The FEATHER (FEbuxostat versus placebo rAndomized controlled
      Trial regarding reduced renal function in patients with Hyperuricemia complicated
      by chRonic kidney disease stage 3) study is a prospective, multicenter, double
      blind, randomized, placebo-controlled trial of febuxostat-a novel, nonpurine,
      selective, xanthine oxidase inhibitor. The present study will enroll, at 64
      medical institutions in Japan, 400 Japanese patients aged 20 years or older who
      have hyperuricemia without gouty arthritis, who present CKD stage 3, and whose
      SUA concentration is 7.1-10.0 mg/dL. Patients are randomly assigned to either the
      febuxostat or the control group, in which febuxostat tablets and placebo are
      administered orally, respectively. The dosage of the study drugs should be one 10
      mg tablet/day at weeks 1 to 4 after study initiation, increased to one 20-mg
      tablet/day at weeks 5 to 8, and elevated to one 40-mg tablet/day at week 9 and
      then maintained until week 108. The primary endpoint is estimated glomerular
      filtration rate (eGFR) slope. The secondary endpoints include the amount and
      percent rate of change in eGFR from baseline to week 108, the amount and percent
      rate of change in SUA concentration from baseline to week 108, the proportion of
      patients who achieved an SUA concentration<=6.0 mg/dL, and the incidence of renal
      function deterioration. DISCUSSION: The present study aims to examine whether
      febuxostat prevents a further reduction in renal function as assessed with eGFR
      in subjects and will (1) provide evidence to indicate the inverse association
      between a reduction in SUA concentration and an improvement in renal function and
      (2) rationalize pharmacotherapy for subjects and clarify its clinical relevance.
      TRIAL REGISTRATION: UMIN Identifier: UMIN000008343.

PMID- 24433287
TI  - The integrin antagonist, cilengitide, is a weak inhibitor of alphaIIbbeta3
      mediated platelet activation and inhibits platelet adhesion under flow.
AB  - The RGD cyclic pentapetide, cilengitide, is a selective inhibitor of alphavbeta3
      and alphavbeta5 integrins and was developed for antiangiogenic therapy. Since
      cilengitide interacts with platelet alphaIIbbeta3 and platelets express alphav
      integrins, the effect of cilengitide on platelet pro-coagulative response and
      adhesion is of interest. Flow-based adhesion assays were performed to evaluate
      platelet adhesion and rolling on von Willebrand factor (vWf), on fibrinogen and
      on human umbilical vein endothelial cells (HUVECs). Flow cytometry was used to
      detect platelet activation (PAC1) and secretion (CD62P) by cilengitide and light
      transmission aggregometry was used to detect cilengitide-dependent platelet
      aggregation. Cilengitide inhibited platelet adhesion to fibrinogen at
      concentrations above 250 uM [which is the Cmax in human studies] and adhesion to
      vWf and HUVECs at higher concentrations under physiologic flow conditions.
      Platelet aggregation was already impaired at cilengitide concentrations >10 uM.
      Activation of alphaIIbbeta3 integrin was inhibited by 250 uM cilengitide, whereas
      platelet secretion was unaffected by cilengitide. No evidence of cilengitide
      induced platelet activation was found at all tested concentrations (0.01-1500
      uM). At higher concentrations, platelet activation was inhibited, predominantly
      due to alphaIIbbeta3 inhibition.

PMID- 24433288
TI  - Deep sequencing of the tobacco mitochondrial transcriptome reveals expressed ORFs
      and numerous editing sites outside coding regions.
AB  - BACKGROUND: The purpose of this study was to sequence and assemble the tobacco
      mitochondrial transcriptome and obtain a genomic-level view of steady-state RNA
      abundance. Plant mitochondrial genomes have a small number of protein coding
      genes with large and variably sized intergenic spaces. In the tobacco mitogenome
      these intergenic spaces contain numerous open reading frames (ORFs) with no clear
      function. RESULTS: The assembled transcriptome revealed distinct monocistronic
      and polycistronic transcripts along with large intergenic spaces with little to
      no detectable RNA. Eighteen of the 117 ORFs were found to have steady-state RNA
      amounts above background in both deep-sequencing and qRT-PCR experiments and ten
      of those were found to be polysome associated. In addition, the assembled
      transcriptome enabled a full mitogenome screen of RNA C->U editing sites. Six
      hundred and thirty five potential edits were found with 557 occurring within
      protein-coding genes, five in tRNA genes, and 73 in non-coding regions. These
      sites were found in every protein-coding transcript in the tobacco mitogenome.
      CONCLUSION: These results suggest that a small number of the ORFs within the
      tobacco mitogenome may produce functional proteins and that RNA editing occurs in
      coding and non-coding regions of mitochondrial transcripts.

PMID- 24433289
TI  - A dimeric PR-1-type pathogenesis-related protein interacts with ToxA and
      potentially mediates ToxA-induced necrosis in sensitive wheat.
AB  - A dimeric PR-1-type pathogenesis-related protein (PR-1-5), recently identified in
      wheat, was found to interact with Stagonospora nodorum ToxA in both yeast two
      hybrid and co-immunoprecipitation assays. Site-specific mutational analyses
      revealed that the RGD motif of ToxA is not targeted by PR-1-5, whereas two
      surface-exposed asparagine residues are essential for the interaction: the N102
      residue of the turning loop between beta2 and beta3 in ToxA and the N141 residue
      of the turning loop between betaC and betaD in PR-1-5. Recombinant PR-1-5 and
      ToxA mutant proteins carrying alanine substitutions at the interacting sites were
      expressed in Pichia pastoris, together with the wild-type proteins. Native
      polyacrylamide gel electrophoresis (PAGE) confirmed that the PR-1-5-N141A mutant
      retains the ability to form dimers. Plant assays indicated that the ToxA-N102A
      mutant fails to induce necrosis, whereas the PR-1-5-N141A mutant is impaired in
      the 'necrosis-promoting' activity shown by the wild-type PR-1-5 when co
      infiltrated with ToxA in sensitive wheat. Reverse transcriptase-polymerase chain
      reaction and Western blot analyses revealed that the native PR-1-5 protein is
      differentially expressed between ToxA-sensitive and ToxA-insensitive wheat lines
      in response to ToxA treatment. These results suggest that PR-1-5 is a potential
      target of ToxA and the site-specific interaction between PR-1-5 and ToxA may
      mediate ToxA-induced necrosis in sensitive wheat. 

PMID- 24433290
TI  - Plasma insulin levels in childhood are related to maternal factors--results of
      the Ulm Birth Cohort Study.
AB  - AIMS: The cardiovascular risk factor profile of a child as well as the
      development of body weight are influenced by genetic and childhood factors.
      Circulating insulin concentrations reflect the metabolic cardiovascular risk and
      may trigger weight gain. We aimed at identifying parental and childhood factors
      which may influence fasting plasma insulin concentrations in children. METHODS:
      The Ulm Birth Cohort study (UBCS) is a prospective birth cohort study. At
      baseline, birth characteristics, maternal pre-pregnancy body mass index (BMI)
      values as well as parental socioeconomic parameters were obtained. At the 8-yr
      follow-up examination, weights, heights, and fasting plasma insulin
      concentrations in n = 422 children and their parents were measured. Offspring of
      women with gestational diabetes mellitus were excluded from statistical analysis.
      RESULTS: Fasting plasma insulin concentrations of children were significantly
      correlated with maternal pre-pregnancy BMI values (r = 0.16) as well as with
      maternal (r = 0.26) but not with paternal fasting plasma insulin concentrations
      (r = 0.11) at the 8-yr follow-up examination. The risk for high fasting plasma
      insulin concentrations (>=75th internal percentile) was 2.30 (1.34-3.92) in
      children who also had high plasma insulin concentrations in umbilical cord blood
      compared to children having lower plasma insulin concentrations (<75th internal
      percentile) in umbilical cord blood. In addition, we observed that children with
      high fasting plasma insulin concentrations at the age of 8 had an altered BMI
      trajectory in childhood, characterized by higher BMI values from the age of 1
      onwards, compared to children with lower insulin concentrations. CONCLUSION: Our
      observations support the hypothesis of perinatal programming of offspring insulin
      concentrations and BMI values by maternal pre-pregnancy BMI values.

PMID- 24433291
TI  - Should brief interventions in primary care address alcohol problems more
      strongly?
AB  - BACKGROUND: Brief interventions have well-established small effects on alcohol
      consumption among hazardous and harmful drinkers in primary care, and national
      large-scale programmes are being implemented in many countries for public health
      reasons. METHODS: This paper examines data from reviews and draws upon older
      brief intervention studies and recent developments in the literature on
      motivational interviewing to consider the capacity of brief interventions to
      benefit those with problems, including those with severe problems. RESULTS:
      Effects on alcohol problems have been shown much less consistently, and evidence
      cannot be claimed to be strong for any outcomes other than reduced consumption.
      Combinations of advice and motivational interviewing are a promising target for
      evaluation in trials, and more detailed studies of the conduct of brief
      interventions are needed. CONCLUSIONS: We propose that brief interventions in
      primary care may be more effective if they offer appropriate content in a person
      centred manner, addressing patient concerns more directly.

PMID- 24433292
TI  - Pericardial, intra-abdominal, and subcutaneous adipose tissue in patients with
      major depressive disorder.
AB  - OBJECTIVE: Major depressive disorder (MDD) is associated with an increased risk
      for developing coronary artery disease (CAD). Recently, pericardial adipose
      tissue, a metabolically active visceral fat depot surrounding the heart, has been
      implicated in the pathogenesis of CAD. Therefore, we investigated pericardial
      adipose tissue volumes in patients with MDD and compared them to healthy
      comparison subjects. METHOD: In this case-control study at a university medical
      center, 50 male and female in-patients with MDD and 25 healthy men and women were
      examined. The main outcome measures were the volumes of pericardial adipose
      tissue, intra-abdominal adipose tissue (IaAT) and subcutaneous adipose tissue
      (ScAT) which were measured using magnetic resonance imaging. RESULTS: The
      pericardial adipose tissue volumes were greater in men and women with MDD
      compared with the healthy comparison group following adjustments for the effects
      of age, weight, height, and physical activity. CONCLUSION: This study expands our
      knowledge about the alterations in body composition that occur in patients with
      MDD. The findings are highly relevant for understanding the comorbidity between
      heart disease and depressive disorders.

PMID- 24433293
TI  - Continuous expression of Otx in the anterior neural lineage is supported by
      different transcriptional regulatory mechanisms during the development of
      Halocynthia roretzi.
AB  - The process of establishing the anterior-posterior axis is an important event in
      the development of bilateral animals. Otx, which encodes a homeodomain
      transcription factor, is continuously expressed in the anterior part of the
      embryo in a wide range of animals. This pattern of expression is thought to be
      important for the formation of anterior neural structures, but the regulatory
      mechanism that sustains the expression is not known. Here, using embryos of the
      ascidian, Halocynthia roretzi, we investigated how the transcription of Otx is
      maintained in the cells of the anterior neural lineage during embryogenesis. We
      identified an enhancer region sufficient to mimic the Otx expression pattern from
      the gastrula to tailbud stages. Several putative transcription factor binding
      sites that are required for generating the Otx expression pattern were also
      identified. Distinct sets of sites were required at different developmental
      stages, suggesting that distinct transcriptional mechanisms regulate Otx
      transcription in each of the gastrula, neurula and tailbud stages. Along with
      previous studies on the transcriptional regulatory mechanism of Otx during the
      pre-gastrula stages, the present results provide the first overview of the
      mechanism that sustains Otx expression in the anterior neural lineage during
      ascidian embryogenesis and demonstrate the complexity of a developmental
      mechanism that maintains Otx transcription. 

PMID- 24433294
TI  - Hepatitis C-related mixed type vitiligo in a patient with Ivemark syndrome.

PMID- 24433295
TI  - Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus.
AB  - Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus
      viruses, including STSV2, did not induce spacer acquisition by the host CRISPR
      immune system. However, coinfection with the tailed fusiform viruses SMV1 and
      STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively
      from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to
      activate adaptation while itself being resistant to CRISPR-mediated adaptation
      and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 +
      STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2
      but not SMV1, acquired spacers from SMV1. This effect was also reproducible on
      reinfecting wild-type host cells with a variant SMV1 isolated from the S-1
      culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind
      DNA. This study also provided evidence for: (i) limits on the maximum sizes of
      CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures;
      (iii) protospacer selection being essentially random and non-directional, and
      (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is
      presented to explain the interactive conflicts between SMV1 and the host CRISPR
      immune system.

PMID- 24433298
TI  - Clinical outcome of 42 dogs with scapular tumors treated by scapulectomy: a
      Veterinary Society of Surgical Oncology (VSSO) retrospective study (1995-2010).
AB  - OBJECTIVE: To report signalment, clinical signs, preoperative staging tests,
      histologic diagnosis, surgical, and oncologic outcomes including postoperative
      limb use, in dogs with scapular tumors treated by scapulectomy. STUDY DESIGN:
      Retrospective case series ANIMALS: Dogs (n = 42) with scapular tumors. METHODS:
      Medical records (1995-2010) from 6 hospitals were searched for dogs with scapular
      tumors treated by scapulectomy. Data retrieved were: signalment, weight,
      percentage of scapula removed, histologic diagnosis, postoperative limb use,
      adjunctive therapy, disease free interval (DFI), and survival time (ST).
      Individual variables were modeled with a Cox proportional hazard model accounting
      for censoring to determine risk factors for decreased DFI and ST. For categorical
      variables, Kaplan-Meier survival plots as well as mean and median survival times
      (MSTs) were calculated. RESULTS: Subtotal scapulectomy was performed in 18 dogs
      (42.9%). Osteosarcoma (OSA) was diagnosed in 27 dogs (64.3%). Limb use was
      evaluated immediately after surgery in 41 dogs. Information on limb use at other
      times (1, 2, 3, and >3 months) postoperatively was also available for some dogs
      and was good to excellent overall. Only adjunctive chemotherapy had a positive
      significant effect on DFI (P = .00011) and ST (P = .0003). CONCLUSION: Canine
      scapular tumors can be treated effectively by scapulectomy and limb use is fair
      to excellent for most dogs. OSA was the most common scapular tumor. Overall
      prognosis for scapular OSA is similar to appendicular OSA at other sites and use
      of adjunctive chemotherapy prolonged the overall DFI and MST.

PMID- 24433299
TI  - The exocytotic machinery.

PMID- 24433300
TI  - Pain care as a human right.

PMID- 24433301
TI  - Impact of smokeless tobacco packaging on perceptions and beliefs among youth,
      young adults, and adults in the U.S: findings from an internet-based cross
      sectional survey.
AB  - BACKGROUND: Research demonstrates that tobacco packaging elements (including
      health warning labels, descriptive characteristics, and corporate branding) are
      associated with knowledge of health risks and product appeal with cigarettes.
      Yet, little research has assessed this with smokeless tobacco (SLT) packaging.
      This study evaluates the association between three SLT packaging elements with
      knowledge of health risks and perceptions of novelty and appeal. Additionally, we
      assess how effects of these messages may differ across age groups, including
      youth (14-17 years), young adults (18-25 years), and older adults (26-65 years).
      METHODS: 1000 participants were administered a web-based survey in 2010 and shown
      three sets of SLT packs in random order, varied by descriptor (flavor descriptor
      vs. none), warning label format (graphic vs. text), and corporate branding
      (branded vs. plain packaging). Participants rated the packs compared with "no
      difference" on appeal, novelty, and risk perceptions associated with product use.
      Chi-square tests were used to test for significant differences in pack
      selections. Multinomial regression was employed to evaluate the association
      between effects of packaging elements and participant age. RESULTS: More
      respondents selected the pack with the graphic warning label as the pack to make
      them consider the health risks associated with SLT use, attract their attention,
      and be least attractive to a smoker. The product with the text warning label was
      the product someone their age would want to be seen using and would appeal to
      peers. The SLT pack with the flavor descriptor was not associated with health
      risks associated with product use. The pack with corporate branding was selected
      as more appealing, to attract attention, and one they would want to be seen
      using; the plain pack was less attractive to smokers. Youth and young adults were
      more likely to indicate that pack elements affected their perceptions of appeal
      and risk associated with SLT products. CONCLUSION: These results suggest that SLT
      pack characteristics have a measurable effect on perceptions of health risk and
      product appeal. Future research should assess these findings in the context of
      harm reduction. Specifically, research is needed to determine whether pack
      elements on SLT products can effectively convey risk and harm.

PMID- 24433302
TI  - Comparison of forelimb and hindlimb systolic blood pressures and proteinuria in
      healthy Shetland Sheepdogs.
AB  - BACKGROUND: The prevalence of systemic hypertension (SHT) in Shetland Sheepdogs
      has not been reported. HYPOTHESIS/OBJECTIVES: SHT is common in Shetland Sheepdogs
      and positively correlated with proteinuria. Measurements of forelimb and hindlimb
      systolic arterial pressure (SAP) are comparable. ANIMALS: Seventy-two clinically
      healthy, client-owned Shetland Sheepdogs. METHODS: Forelimb and hindlimb SAP were
      recorded by Doppler ultrasonography. Proteinuria was quantified by urine
      dipstick, microalbuminuria, and protein:creatinine ratio (UPC). The relationship
      of UPC, anxiety, age, weight, and heart rate with forelimb SAP was evaluated.
      RESULTS: The mean forelimb and hindlimb SAP were 132 +/- 20 and 118 +/- 20 mmHg,
      respectively. The SAP exceeded 160 mmHg in 9 dogs, suggesting 13% prevalence of
      SHT. Four dogs had a UPC above 0.5; 2 of these had forelimb SAP exceeding 160
      mmHg. Correlation of forelimb and hindlimb SAP was poor (r(2)  = 0.09; P = .011).
      Bland-Altman plots revealed substantial bias (-14 mmHg) between limb measurements
      with clinically unacceptable 95% limits of agreement (-60 to 33 mmHg). There was
      no correlation between forelimb SAP and UPC (P = .06) or anxiety level (P = .49).
      Age (P < .0001) and heart rate (P = .038) were significant predictors of forelimb
      SAP; weight (P = .73) was not. CONCLUSIONS: Prevalence of SHT was 13% and not
      correlated with proteinuria. Forelimb and hindlimb SAP were poorly correlated;
      therefore, trends in an individual animal should be monitored using the same
      measurement site. Additionally, values for Doppler SAP were determined in
      Shetland Sheepdogs.

PMID- 24433303
TI  - Regulating fatty acids in infant formula: critical assessment of U.S. policies
      and practices.
AB  - BACKGROUND: Fatty acids in breast-milk such as docosahexaenoic acid and
      arachidonic acid, commonly known as DHA and ARA, contribute to the healthy
      development of children in various ways. However, the manufactured versions that
      are added to infant formula might not have the same health benefits as those in
      breast-milk. There is evidence that the manufactured additives might cause harm
      to infants' health, and they might lead to unwarranted increases in the cost of
      infant formula.The addition of such fatty acids to infant formula needs to be
      regulated. In the U.S., the Food and Drug Administration has primary
      responsibility for regulating the composition of infant formula. The central
      purpose of this study is to assess the FDA's efforts with regard to the
      regulation of fatty acids in infant formula. METHODS: This study is based on
      critical analysis of policies and practices described in publicly available
      documents of the FDA, the manufacturers of fatty acids, and other relevant
      organizations. The broad framework for this work was set out by the author in his
      book on Regulating Infant Formula, published in 2011. RESULTS: The FDA does not
      assess the safety or the health impacts of fatty acid additives to infant formula
      before they are marketed, and there is no systematic assessment after marketing
      is underway. Rather than making its own independent assessments, the FDA accepts
      the manufacturers' claims regarding their products' safety and effectiveness.
      CONCLUSIONS: The FDA is not adequately regulating the use of fatty acid additives
      to infant formula. This results in exposure of infants to potential risks.
      Adverse reactions are already on record. Also, the additives have led to
      increasing costs of infant formula despite the lack of proven benefits to normal,
      full term infants. There is a need for more effective regulation of DHA and ARA
      additives to infant formula.

PMID- 24433304
TI  - Influenza vaccines and influenza antiviral drugs in Africa: are they available
      and do guidelines for their use exist?
AB  - BACKGROUND: Influenza viruses cause significant morbidity and mortality in
      Africa, particularly among high-risk groups, but influenza vaccines and antiviral
      drugs may not be commonly available and used. The main aim of this study was to
      determine the availability and use of influenza vaccines and antiviral drugs as
      well as to describe existing related guidelines and policies in Africa. METHODS:
      A self-administered survey was distributed among key influenza experts in 40
      African countries. RESULTS: Of the 40 countries surveyed, 31 (78%) responded;
      14/31 (45%) reported availability of seasonal influenza vaccine, and 19/31 (65%)
      reported availability of antiviral drugs for the treatment of influenza. Vaccine
      coverage data were only available for 4/14 (29%) countries that reported
      availability of seasonal influenza vaccine and ranged from <0.5% to 2% of the
      population. CONCLUSIONS: Influenza vaccines and antiviral drugs are available in
      many countries in Africa but coverage estimates are low and remain largely
      unknown. Describing the local burden of disease and identifying funding are
      essential to encourage countries to use influenza vaccine more widely.

PMID- 24433305
TI  - Modeled effectiveness of ventilation with contaminant control devices on indoor
      air quality in a swine farrowing facility.
AB  - Because adverse health effects experienced by swine farm workers in concentrated
      animal feeding operations (CAFOs) have been associated with exposure to dust and
      gases, efforts to reduce exposures are warranted, particularly in winter seasons
      when exposures increase due to decreased ventilation. Simulation of air quality
      and operating costs for ventilating swine CAFO, including treating and
      recirculating air through a farrowing room, was performed using mass and energy
      balance equations over a 90-day winter season. System operation required
      controlling heater operation to achieve room temperatures optimal to ensure
      animal health (20 to 22.5  degrees C). Five air pollution control devices, four
      room ventilation rates, and five recirculation patterns were examined. Inhalable
      dust concentrations were easily reduced using standard industrial air pollution
      control devices, including a cyclone, filtration, and electrostatic precipitator.
      Operating ventilation systems at 0.94 m3 s(-1) (2000 cfm) with 75 to 100%
      recirculation of treated air from cyclone, electrostatic precipitator, and shaker
      dust filtration system achieves adequate particle control with operating costs
      under $1.00 per pig produced ($0.22 to 0.54), although carbon dioxide (CO2)
      concentrations approach 2000 ppm using in-room ventilated gas fired heaters. In
      no simulation were CO2 concentrations below industry recommended concentrations
      (1540 ppm), but alternative heating devices could reduce CO2 to acceptable
      concentrations. While this investigation does not represent all production swine
      farrowing barns, which differ in characteristics including room dimensions and
      swine occupancy, the simulation model and ventilation optimization methods can be
      applied to other production sites. This work shows that ventilation may be a cost
      effective control option in the swine industry to reduce exposures.

PMID- 24433306
TI  - Dental procedures in 24 patients with chronic immune thrombocytopenia in
      prospective clinical studies of eltrombopag.
AB  - Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by
      chronically low peripheral blood platelet counts. Eltrombopag is an oral, non
      peptide, thrombopoietin-receptor agonist that increases platelet production. This
      report examines peri-procedural platelet counts and bleeding complications among
      chronic ITP patients requiring dental procedures while participating in clinical
      studies with eltrombopag. A total of 494 patients participated in five clinical
      studies of eltrombopag in chronic ITP. Information about dental procedures was
      collected prospectively in four studies and retrospectively in one study. Twenty
      four patients (22 eltrombopag, 2 placebo) underwent 32 dental procedures (dental
      cleaning, tooth repair, artificial crown, dental prosthesis, tooth extraction,
      dental or wisdom teeth extraction, dental root extraction, and endodontic
      procedures, among others) during study treatment or up to 10 days later.
      Supplemental ITP therapy (e.g., corticosteroids, platelet transfusions) was given
      before the dental procedure to increase platelet counts in three eltrombopag
      treated patients and both placebo-treated patients. The mean pre-procedure
      platelet count +/- standard deviation for all procedures in the overall
      population of patients, eltrombopag group, and placebo group prior to undergoing
      dental procedures was 96 000 +/- 81 069/ul,103 517 +/- 81 522/ul, and 23 333 +/-
      9291/ul, respectively. Two patients in each group had platelet counts below 30
      000/ul before the procedure. No patient who had a dental procedure experienced a
      bleeding adverse event. Among patients with chronic ITP who required a dental
      procedure during clinical studies of eltrombopag, supplemental ITP treatment was
      required for both patients who received placebo but was not required for most
      patients who received eltrombopag. No bleeding complications were reported. These
      data imply that patients with chronic ITP who receive eltrombopag and experience
      increases in platelet counts fulfill current pre-procedural platelet count
      recommendations to undergo invasive dental procedures, and may have a lower risk
      of bleeding complications and a reduced need for supplemental ITP treatment.

PMID- 24433308
TI  - Cardiac sarcoidosis: electrophysiological outcomes on long-term follow-up and the
      role of the implantable cardioverter-defibrillator.
AB  - OBJECTIVES: The objectives of this study were to identify the predictors of life
      threatening ventricular arrhythmias in patients with cardiac sarcoidosis (CS) and
      to evaluate the role of the implantable cardioverter-defibrillator (ICD) in this
      patient population. BACKGROUND: ICD implantation is a class IIA recommendation
      for patients with CS. However, some indications for ICD implantation in CS
      patients are still unclear and not enough data are available to establish
      predictors of malignant ventricular tachyarrhythmias in this group of patients.
      METHODS: We retrospectively identified all consecutive patients who were
      diagnosed with CS, during the period from March 2002 to April 2010. Cardiac
      rhythm devices were regularly interrogated and clinical data recorded during
      follow-up visits. RESULTS: Thirty-three patients (17 male) with CS were
      identified. The mean age was 53 +/- 11. The mean left ventricular ejection
      fraction (LVEF) was 41 +/- 18%. Thirty patients received an ICD. Twelve patients
      (36.3%) had sustained ventricular arrhythmias. Eleven patients received
      appropriate therapies and 9 patients received inappropriate shocks, representing
      36.7% and 30.0% of the ICD population, respectively. Patients who received
      appropriate ICD therapies were younger with mean age 47.4 +/- 7.8, and had a
      lower mean LVEF 33.0 +/- 12.0 compared to those who did not receive ICD therapies
      (P = 0.0301 and 0.0341, respectively). There were no other demographic, clinical,
      electrocardiographic, electrophysiological, or imaging markers that predicted the
      future occurrence of appropriate ICD therapies in our cohort of patients.
      CONCLUSIONS: CS is strongly associated with malignant ventricular arrhythmias. No
      specific predictors of such tachyarrhythmias emerged, other than young age and
      low LVEF.

PMID- 24433307
TI  - Clopidogrel enhances periodontal repair in rats through decreased inflammation.
AB  - AIM: We hypothesized that platelet inactivation induced by drugs might interfere
      with periodontal repair in experimental periodontitis by suppressing the release
      of biological mediators from platelets at the site of injury. MATERIAL AND
      METHODS: Sixty rats were randomly assigned to six groups (n = 10) and ligatures
      were placed around lower first molars of three groups. The other three groups
      were used as negative controls. Ligatures were removed after 10 days of
      periodontitis induction and all groups were submitted to treatment with aspirin
      (Asp) (30 mg/kg), clopidogrel (Clop) (75 mg/kg) or NaCl 0.9% intra-gastrically
      once daily for 3 days. Periodontal tissue was assessed by the measurement of
      CXCL12, CXCL4, CCL5 and platelet-derived growth factor (PDGF) by enzyme-linked
      immunosorbent assay; histomorphometrical analysis of polymorphonuclear (PMN)
      infiltration, attachment loss, bone loss and osteoclast numbers and
      quantification of blood vessels by imunnohistochemistry. RESULTS: During
      periodontal repair and treatment with NaCl 0.9%, CCL5 was decreased and CXCL12
      increased when compared with negative control groups. Asp and Clop did not affect
      CCL5 expression, decreased CXCL12 but only Clop decreased CXCL4 and PDGF content
      compared with saline-treated animals. Clop increased blood vessel number, reduced
      PMN count and decreased attachment and bone loss, also decreased osteoclast
      number in animals submitted or not to periodontal repair. CONCLUSION: Systemic
      administration of Clop for 3 days improved the repair process associated with
      experimental periodontal disease, suggesting that it may have therapeutic value
      under situations where tissues undergo a transition from inflammation to repair.

PMID- 24433310
TI  - Associations between predictors of children's dietary intake and socioeconomic
      position: a systematic review of the literature.
AB  - Socioeconomically disadvantaged children are at higher risk of consuming poor
      diets, in particular less fruits and vegetables and more non-core foods and
      sweetened beverages. Currently the drivers of socioeconomically related
      differences in children's dietary intake are not well understood. This systematic
      review explored whether dietary predictors vary for children of different
      socioeconomic circumstances. Seven databases and reference lists of included
      material were searched for studies investigating predictors of 9-13-year-old
      children's diet in relation to socioeconomic position. Individual- and population
      based cross-sectional, cohort and epidemiological studies published in English
      and conducted in developed countries were included. Twenty-eight studies were
      included in this review; most were conducted in Europe (n = 12) or North America
      (n = 10). The most frequently used indicators of socioeconomic position were
      parent education and occupation. Predictors of children's dietary intake varied
      among children of different socioeconomic circumstances. Socioeconomic position
      was consistently associated with children's nutrition knowledge, parent
      modelling, home food availability and accessibility. Indeterminate associations
      with socioeconomic position were observed for parent feeding practices and food
      environment near school. Differences in the determinants of eating between
      socioeconomic groups provide a better understanding of the drivers of
      socioeconomic disparities in dietary intake, and how to develop targeted
      intervention strategies. 

PMID- 24433309
TI  - Mycobacterium bovis BCG infection severely delays Trichuris muris expulsion and
      co-infection suppresses immune responsiveness to both pathogens.
AB  - BACKGROUND: The global epidemiology of parasitic helminths and mycobacterial
      infections display extensive geographical overlap, especially in the rural and
      urban communities of developing countries. We investigated whether co-infection
      with the gastrointestinal tract-restricted helminth, Trichuris muris, and the
      intracellular bacterium, Mycobacterium bovis (M. bovis) BCG, would alter host
      immune responses to, or the pathological effect of, either infection. RESULTS: We
      demonstrate that both pathogens are capable of negatively affecting local and
      systemic immune responses towards each other by modifying cytokine phenotypes and
      by inducing general immune suppression. T. muris infection influenced non
      specific and pathogen-specific immunity to M. bovis BCG by down-regulating
      pulmonary TH1 and Treg responses and inducing systemic TH2 responses. However, co
      infection did not alter mycobacterial multiplication or dissemination and host
      pulmonary histopathology remained unaffected compared to BCG-only infected mice.
      Interestingly, prior M. bovis BCG infection significantly delayed helminth
      clearance and increased intestinal crypt cell proliferation in BALB/c mice. This
      was accompanied by a significant reduction in systemic helminth-specific TH1 and
      TH2 cytokine responses and significantly reduced local TH1 and TH2 responses in
      comparison to T. muris-only infected mice. CONCLUSION: Our data demonstrate that
      co-infection with pathogens inducing opposing immune phenotypes, can have
      differential effects on compartmentalized host immune protection to either
      pathogen. In spite of local and systemic decreases in TH1 and increases in TH2
      responses co-infected mice clear M. bovis BCG at the same rate as BCG only
      infected animals, whereas prior mycobacterial infection initiates prolonged worm
      infestation in parallel to decreased pathogen-specific TH2 cytokine production.

PMID- 24433311
TI  - Introduction and commentary for special issue on health information technology.

PMID- 24433312
TI  - School readiness of children with cerebral palsy.
AB  - AIM: To examine school readiness in preschool-age children with cerebral palsy
      (CP) on three of five domains compared with reported norms of children with
      typical development (CTD). METHOD: A representative population of 151 preschool
      age children with CP (87 males, 64 females; 131 [87%] with spasticity, 17 [11%]
      dyskinesia, 3 [4%] hypotonia) were assessed at 48 or 60 months corrected age.
      Children were functioning in the following Gross Motor Function Classification
      System (GMFCS) levels: I, 74 (49%); II, 17 (11%); III, 14 (9%); IV, 26 (17%); V,
      20 (13%). Children's motor performance, self-care, and social function were
      assessed using the Pediatric Evaluation of Disability Inventory (PEDI) and
      communication using the Communication and Symbolic Behaviour Scales Developmental
      Profile (CSBS-DP). Results were compared with a reference sample of CTD (PEDI CTD
      n=412; CSBS-DP CTD n=790). Linear regression was used to compare these data by
      functional severity. RESULTS: Children with CP had significantly lower PEDI
      scores in all domains than CTD. Self-care scores ranged from 0.5 to more than 4SD
      below CTD, motor performance was 2 to >4SD below CTD, and social function between
      0.5 and >4SD below CTD. Fifty-five per cent of children demonstrated
      significantly delayed communication skills. Non-ambulant children displayed
      significantly lower scores than ambulant children. INTERPRETATION: Preschool-age
      children with CP perform significantly below their peers in three of five key
      readiness-to-learn skill areas including mobility, self-care, social function,
      and communication abilities. Broader emphasis needs to be placed on multimodal
      screening and intervention to prepare children with CP for school entry.

PMID- 24433313
TI  - A systematic review of controlled interventions to reduce overweight and obesity
      in people with schizophrenia.
AB  - OBJECTIVE: Overweight and obesity are generally found among patients with
      schizophrenia. This may lead to serious implications for health and wellbeing.
      The aim was to review controlled intervention studies on reducing
      overweight/obesity and/or reducing physical illness in patients with
      schizophrenia. METHOD: A systematic literature search was carried out in the
      bibliographic databases PubMed (MEDLINE), Embase (Ovid), PsycInfo (Ovid) and
      Cinahl (Ebsco). We included all randomised and non-randomised clinically
      controlled studies that compared a non-pharmacological intervention, aimed at
      weight reduction and/or reducing physical illness, with standard care for
      patients with schizophrenia. RESULTS: All 1713 references were evaluated for
      inclusion in the review. Twenty-three met the inclusion criteria and were
      categorised into four subgroups according to tested interventions: diet, exercise
      and cognitive behavioural therapy, or mixed combinations of the three. In this
      review, interventions showed efficacy in reducing weight and improving physical
      health parameters confirming that physical health improvement was possible in
      patients with schizophrenia. CONCLUSION: The included studies indicate that the
      interventions reduced weight and improved physical health parameters in patients
      with schizophrenia.

PMID- 24433314
TI  - Hermansky-Pudlak syndrome type 4 with a novel mutation.

PMID- 24433315
TI  - A novel mutation in GATA6 causes pancreatic agenesis.
AB  - Heterozygous mutations in GATA6 have been linked to pancreatic agenesis and
      cardiac malformations. The aim of this study was to describe a new mutation in
      GATA6 in an infant with pancreatic agenesis, associated with truncus arteriosus
      and absent gallbladder. Clinical data were obtained from chart review. Gene
      sequencing was performed on genomic DNA. The patient was a female infant
      diagnosed shortly after birth with a severe cardiac malformation, absent
      gallbladder, anomalous hepatic blood flow, unilateral hydronephrosis and
      hydroureter, neonatal diabetes, and pancreatic exocrine insufficiency. Despite
      prolonged intensive management care, she died at 3 months of age because of
      cardiac complications. Analysis of her genomic DNA revealed a novel missense
      mutation of GATA6. The novel mutation described in this case extends the list of
      GATA6 mutations causing pancreatic agenesis and cardiac malformations. 

PMID- 24433316
TI  - De novo 13q13.3-21.31 deletion involving RB1 gene in a patient with
      hemangioendothelioma of the liver.
AB  - Interstitial deletions of the long arm of chromosome 13 (13q) are related with
      variable phenotypes, according to the size and the location of the deleted
      region. The main clinical features are moderate/severe mental and growth
      retardation, cranio-facial dysmorphism, variable congenital defects and increased
      susceptibility to tumors. Here we report a 3-year-old girl carrying a de novo
      13q13.3-21.32 interstitial deletion. She showed developmental delay, growth
      retardation and mild dysmorphism including curly hair, high forehead, short nose,
      thin upper lip and long philtrum. An abnormal mass was surgically removed from
      her liver resulting in a hemangioendothelioma. Array analysis allowed us to
      define a deleted region of about 27.87 Mb, which includes the RB1 gene. This is
      the first report of a 13q deletion associated with infantile hemangioendothelioma
      of the liver.

PMID- 24433317
TI  - Does a continuous local anaesthetic pain treatment after immediate tissue
      expander reconstruction in breast carcinoma patients more efficiently reduce
      acute postoperative pain--a prospective randomised study.
AB  - BACKGROUND: Immediate breast reconstruction with an expander is a reasonable
      option for properly selected patients. After reconstruction, patients have severe
      postoperative pain, which responds poorly to opioids. Our aim was to evaluate if
      continuous wound infusion of a local anaesthetic into the surgical wound reduces
      postoperative pain, consumption of opioids and incidence of chronic pain compared
      to standard intravenous piritramide after primary breast reconstruction in breast
      carcinoma patients. METHODS: Altogether, 60 patients were enrolled in our study;
      one half in the group with wound infusion of a local anaesthetic, and the other
      half in the standard (piritramide) group. Parameters measured included: pain
      intensity (visual analogue scale), drug requirements, alertness, hospitalisation,
      side-effects and late complications. A p-value of < 0.05 was considered
      statistically significant. RESULTS: In the recovery room, the test group reported
      less acute pain at rest (P = 0.03) and at activity (P = 0.01), and on the day of
      the surgical procedure they reported less pain at activity (P = 0.003).
      Consumption of piritramide and metoclopramide was lower in this group (P <
      0.0001), but their alertness after the surgical procedure was higher compared to
      the standard group (P < 0.001). After three months, the test group reported less
      chronic pain (P = 0.01). CONCLUSIONS: After primary tissue expander breast
      reconstruction, wound infusion of a local anaesthetic significantly reduces acute
      pain and enables reduced opioid consumption, resulting in less postoperative
      sedation and reduced need for antiemetic drugs. Wound infusion of a local
      anaesthetic reduces chronic pain.

PMID- 24433318
TI  - Clinical outcome after intra-articular administration of bone marrow derived
      mesenchymal stem cells in 33 horses with stifle injury.
AB  - OBJECTIVE: To report outcome of horses with femorotibial lesions (meniscal,
      cartilage or ligamentous) treated with surgery and intra-articular administration
      of autologous bone marrow derived mesenchymal stem cells (BMSCs). STUDY DESIGN:
      Prospective case series. ANIMALS: Horses (n = 33). METHODS: Inclusion criteria
      included horses that had lameness localized to the stifle by diagnostic
      anesthesia, exploratory stifle arthroscopy and subsequent intra-articular
      administration of autologous BMSCs. Case details and follow-up were gathered from
      medical records, owner, trainer or veterinarian. Outcome was defined as returned
      to previous level of work, returned to work, or failed to return to work.
      RESULTS: Follow-up (mean, 24 months) was obtained; 43% of horses returned to
      previous level of work, 33% returned to work, and 24% failed to return to work.
      In horses with meniscal damage (n = 24) a higher percentage in the current study
      (75%) returned to some level of work compared to those in previous reports (60
      63%) that were treated with arthroscopy alone, which resulted in a statistically
      significant difference between studies (P = .038). Joint flare post injection was
      reported in 3 horses (9.0%); however, no long-term effects were noted.
      CONCLUSIONS: Intra-articular administration of BMSC postoperatively for stifle
      lesions appeared to be safe, with morbidity being similar to that of other
      biologic agents. Improvement in ability to return to work may be realized with
      BMSC treatment compared to surgery alone in horses with stifle injury.

PMID- 24433320
TI  - Depression in informal caregivers of persons with dementia.
AB  - BACKGROUND: Worldwide, there are more than 35 million individuals diagnosed with
      Alzheimer's disease. Many of these individuals are cared for at home by unpaid
      caregivers who often report high levels of depressive symptoms and depression.
      The majority of studies conducted to predict which caregivers are at risk for
      depression have examined non-modifiable risk factors. Therefore, it is important
      to discover modifiable factors that may be associated with risk for depression in
      caregivers. OBJECTIVES: The aims of this research were to identify a set of
      factors that are modifiable and known to be associated with high levels of
      depression/depressive symptomology (D/DS) in other populations and to determine
      whether these factors are predictive of D/DS after controlling for non
      modifiable, demographic, and clinical factors. DESIGN: Secondary data analysis.
      METHODS: Fifty-three participants provided direct care to a person with dementia
      with night-time activity. Inclusion criteria included not undergoing treatment
      for sleep disorders; living with the care recipient; and a Mini-Mental Status
      Exam score > 27. Baseline data collected by questionnaires, sleep diary and
      actigraphy. RESULTS: In multivariate analyses of the modifiable factors, only
      high levels of negative affect predicted higher levels of depressive
      symptomatology. When non-modifiable factors were included in the model, negative
      affect and high levels of perceived caregiver burden predicted 52.6% of the
      variance in depressive symptomology. In secondary analyses, wake after sleep
      onset misperception was associated with higher depression scores. CONCLUSIONS:
      While negative affect had a moderate effect on depressive symptoms, modifiable
      factors often associated with depressive symptoms in other studies were not
      associated with caregiver depression in this study. Possibly caregivers' overall
      poor sleep causes a floor effect and masks a potential relationship. IMPLICATIONS
      FOR PRACTICE: Both caregivers' affect and perceived burden are strongly related
      to depressive symptoms, so healthcare practitioners need to frequently assess
      both so as to provide timely interventions.

PMID- 24433319
TI  - Comparison of 4 direct Coombs' test methods with polyclonal antiglobulins in
      anemic and nonanemic dogs for in-clinic or laboratory use.
AB  - BACKGROUND: Difficulties with the direct antiglobulin test (DAT) and its apparent
      lack of sensitivity and specificity for immune-mediated hemolytic anemia (IMHA)
      in dogs have raised skepticism regarding its diagnostic value. OBJECTIVE: To
      compare different DATs and other hematologic parameters in dogs. ANIMALS:
      Anticoagulated blood samples from 59 nonanemic and 46 anemic dogs (+/- IMHA) from
      a research colony and veterinary clinics. METHODS: Prospective observational
      study: Immunochromatographic strip, gel microcolumn, and capillary techniques
      were compared with standard microtiter DAT using 2 polyvalent antiglobulins.
      Spherocytosis, autoagglutination, osmotic fragility, and clinical data were
      assessed. RESULTS: Blood samples from all 59 nonanemic dogs were DAT-. Among 46
      anemic dogs, 33 were suspected of IMHA, but only 20 were DAT+. Old and new DAT
      methods yielded comparable and consistent results even after storage of chilled
      blood samples for 1 week. Spherocytosis and autoagglutination (that did not
      persist after washing) were noted in 15 and 16 DAT+ dogs, respectively. The other
      26 anemic dogs, including 21 previously transfused dogs and 4 with
      autoagglutination, tested DAT- by the other methods. Osmotic fragility was
      increased in 70% (19/27) of anemic and all 15 DAT+ dogs tested. Limited follow-up
      testing revealed DAT+ results for 3-70 days. CONCLUSIONS AND CLINICAL IMPORTANCE:
      The novel strip and capillary DAT methods are promising adjunct in-clinic tools.
      Despite prior immunosuppressive treatment and presence of autoagglutination, the
      DAT was positive in anemic dogs with IMHA. Transfusion did not cause false DAT+
      results. Our results support DAT as a cornerstone in the diagnosis of canine
      IMHA.

PMID- 24433321
TI  - Presence of infectious agents and co-infections in diarrheic dogs determined with
      a real-time polymerase chain reaction-based panel.
AB  - BACKGROUND: Infectious diarrhea can be caused by bacteria, viruses, or protozoan
      organisms, or a combination of these. The identification of co-infections in dogs
      is important to determine the prognosis and to plan strategies for their
      treatment and prophylaxis. Although many pathogens have been individually
      detected with real-time polymerase chain reaction (PCR), a comprehensive panel of
      agents that cause diarrhea in privately owned dogs has not yet been established.
      The objective of this study was to use a real-time PCR diarrhea panel to survey
      the frequencies of pathogens and co-infections in owned dogs attended in a
      veterinary hospital with and without diarrhea, as well the frequency in different
      countries. Feces samples were tested for canine distemper virus, canine
      coronavirus, canine parvovirus type 2 (CPV-2), Clostridium perfringens alpha
      toxin (CPA), Cryptosporidium spp., Giardia spp., and Salmonella spp. using
      molecular techniques. RESULTS: In total, 104 diarrheic and 43 control dogs that
      were presented consecutively at a major private veterinary hospital were included
      in the study. Overall, 71/104 (68.3%) dogs with diarrhea were positive for at
      least one pathogen: a single infection in 39/71 dogs (54.9%) and co-infections in
      32/71 dogs (45.1%), including 21/32 dogs (65.6%) with dual, 5/32 (15.6%) with
      triple, and 6/32 (18.8%) with quadruple infections. In the control group, 13/43
      (30.2%) dogs were positive, all with single infections only. The most prevalent
      pathogens in the diarrheic dogs were CPA (40/104 dogs, 38.5%), CPV-2 (36/104
      dogs, 34.6%), and Giardia spp. (14/104 dogs, 13.5%). CPV-2 was the most prevalent
      pathogen in the dual co-infections, associated with CPA, Cryptosporidium spp., or
      Giardia spp. No statistical difference (P = 0.8374) was observed in the duration
      of diarrhea or the number of deaths (P = 0.5722) in the presence or absence of
      single or co-infections. CONCLUSIONS: Diarrheic dogs showed a higher prevalence
      of pathogen infections than the controls. Whereas the healthy dogs had only
      single infections, about half the diarrheic dogs had co-infections. Therefore,
      multiple pathogens should be investigated in dogs presenting with diarrhea. The
      effects of multiple pathogens on the disease outcomes remain unclear because the
      rate of death and the duration of diarrhea did not seem to be affected by these
      factors.

PMID- 24433322
TI  - ROS-mediated activation of Drosophila larval nociceptor neurons by UVC
      irradiation.
AB  - BACKGROUND: The complex Drosophila larval peripheral nervous system, capable of
      monitoring sensory input from the external environment, includes a family of
      multiple dendritic (md) neurons with extensive dendritic arbors tiling the inner
      surface of the larval body wall. The class IV multiple dendritic (mdIV) neurons
      are the most complex with dendritic nerve endings forming direct intimate
      contacts with epithelial cells of the larval body wall. Functioning as polymodal
      mechanonociceptors with the ability to respond to both noxious mechanical
      stimulation and noxious heat, the mdIV neurons are also activated by nanomolar
      levels of the endogenous reactive oxygen species (ROS), H2O2. Although often
      associated with tissue damage related to oxidative stress, endogenous ROS have
      also been shown to function as signaling molecules at lower concentrations. The
      overall role of ROS in sensory signaling is poorly understood but the acutely
      sensitive response of mdIV neurons to ROS-mediated activation is consistent with
      a routine role in the regulation of mdIV neuronal activity. Larvae respond to
      short wavelength ultraviolet (UVC) light with an immediate and visual system
      independent writhing and twisting of the body previously described as a
      nociceptive response. Molecular and cellular mechanisms mediating this response
      and potential relationships with ROS generation are not well understood. We have
      used the UVC-induced writhing response as a model for investigation of the
      proposed link between endogenous ROS production and mdIV neuron function in the
      larval body wall. RESULTS: Transgenic inactivation of mdIV neurons caused a
      strong suppression of UVC-induced writhing behavior consistent with a key role
      for the mdIV neurons as mediators of the behavioral response. Direct imaging of
      ROS-activated fluorescence showed that UVC irradiation caused a significant
      increase in endogenous ROS levels in the larval body wall and transgenic
      overexpression of antioxidant enzymes strongly suppressed the UVC-induced
      writhing response. Direct electrophysiological recordings demonstrated that UVC
      irradiation also increased neuronal activity of the mdIV neurons. CONCLUSIONS:
      Results obtained using UVC irradiation to induce ROS generation provide evidence
      that UVC-induced writhing behavior is mediated by endogenous production of ROS
      capable of activating mdIV mechanonociceptors in the larval body wall.

PMID- 24433323
TI  - The changing food outlet distributions and local contextual factors in the United
      States.
AB  - BACKGROUND: Little is known about the dynamics of the food outlet distributions
      associated with local contextual factors in the U.S. This study examines the
      changes in food stores/services at the 5-digit Zip Code Tabulated Area (ZCTA5)
      level in the U.S., and assesses contextual factors associated with the changes.
      METHODS: Data from 27,878 ZCTA5s in the contiguous United States without an
      extreme change in the number of 6 types of food stores/services (supermarkets,
      small-size grocery stores, convenience stores, fresh/specialty food markets,
      carry-out restaurants, and full-service restaurants) were used. ZCTA5s'
      contextual factors were from the 2000 Census. Numbers of food stores/services
      were derived from the Census Business Pattern databases. Linear regression models
      assessed contextual factors' influences (racial/ethnic compositions, poverty
      rate, urbanization level, and foreign-born population%) on 1-year changes in food
      stores/services during 2000-2001, adjusted for population size, total business
      change, and census regions. RESULTS: Small-size grocery stores and
      fresh/specialty food markets increased more and convenience stores decreased more
      in Hispanic-predominant than other areas. Among supermarket-free places, new
      supermarkets were less likely to be introduced into black-predominant than white
      predominant areas (odds ratio (OR) = 0.52, 95% CI = 0.30-0.92). However, among
      areas without the following type of store at baseline, supermarket (OR = 0.48
      (0.33-0.70)), small-size grocery stores (OR = 1.32 (1.08-1.62)), and
      fresh/specialty food markets (OR = 0.70 (0.53-0.92)) were less likely to be
      introduced into areas of low foreign-born population than into areas of high
      foreign-born population. Higher poverty rate was associated with a greater
      decrease in supermarket, a less decrease in small-size grocery stores, and a less
      increase in carry-out restaurants (all p for trends <0.001). Urban areas
      experienced more increases in full-service and carry-out restaurants than
      suburban areas. CONCLUSIONS: Local area characteristics affect 1-year changes in
      food environment in the U.S. Hispanic population was associated with more food
      stores/services capable of supplying fresh food items. Black-predominant and
      poverty-afflicted areas had a greater decrease in supermarkets. Full-service and
      carry-out restaurants increased more in urban than suburban areas. Foreign-born
      population density was associated with introduction of grocery stores and
      fresh/specialty food markets into the areas.

PMID- 24433324
TI  - Real-time contact force sensing for pulmonary vein isolation in the setting of
      paroxysmal atrial fibrillation: procedural and 1-year results.
AB  - INTRODUCTION: The additional benefit of contact force (CF) technology during
      pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (AF) to improve
      mid-term clinical outcome is unclear. METHODS AND RESULTS: Eligible patients with
      symptomatic paroxysmal AF were enrolled in this prospective trial, comparing
      circular antral catheter ablation (guided by Carto 3 System, Biosense Webster)
      using either a new open-irrigated CF catheter (SmartTouch Thermocool, Biosense
      Webster) (CF group) or a non-CF open-irrigated catheter (EZ Steer Thermocool,
      Biosense Webster) (control group). Overall, 30 patients were enrolled in each
      group, with a standardized 12-month follow-up, free of antiarrhythmic therapy.
      Demographic, cardiovascular and anatomic characteristics were similar in both
      groups. Though complete PVI was eventually achieved in all cases in both groups,
      success using an exclusive anatomic approach was 80.0% in CF group versus 36.7%
      in control group (P < 0.0001). CF use was associated with significant reductions
      in fluoroscopy exposure (P < 0.01) and radiofrequency time (P = 0.01). The
      incidence rates of AF recurrence were 10.5% (95% CI, 1.38-22.4) in the CF group,
      and 35.9% (95% CI, 12.4-59.4) in the control group (log rank test, P = 0.04).
      After adjustment on potential confounders, the use of CF catheter was found to be
      associated with a lower AF recurrence (OR 0.18, 95% CI 0.04-0.94, P = 0.04).
      CONCLUSION: Our findings suggest a potential benefit of real-time CF sensing
      technology, in reducing AF recurrence during the first year after PVI.

PMID- 24433326
TI  - A clinical trial of active hearing protection for orchestral musicians.
AB  - Orchestral musicians-an at-risk group for noise-induced hearing loss-have
      consistently reported great difficulty using hearing protection while performing
      or rehearsing, even when using earplugs specifically designed for musicians. A
      recent innovation in this field has been electronic earplugs that claim to
      deliver very high quality sound and only attenuate when sound levels become
      excessive. This study investigated these claims, aiming to determine whether
      professional orchestral musicians were able to use these devices and whether they
      were preferred to existing earplugs. Initially clinical and laboratory testing
      was carried out on the devices, indicating some spectral alteration of processed
      sound occurred, however claims of attenuation properties were validated.
      Following this, 26 orchestral musicians used the devices during rehearsals and
      performances for at least four weeks, providing feedback throughout this period.
      While musicians preferred the devices to previous earplugs, they identified
      issues including difficulty with orchestral balance, perception of dynamics and
      quality of sound provided by the devices. Results indicate these earplugs are a
      very positive step towards a usable hearing conservation tool for orchestral
      musicians to use in conjunction with other risk mitigation measures.

PMID- 24433325
TI  - Associations of HLA alleles with specific language impairment.
AB  - BACKGROUND: Human leukocyte antigen (HLA) loci have been implicated in several
      neurodevelopmental disorders in which language is affected. However, to date, no
      studies have investigated the possible involvement of HLA loci in specific
      language impairment (SLI), a disorder that is defined primarily upon unexpected
      language impairment. We report association analyses of single-nucleotide
      polymorphisms (SNPs) and HLA types in a cohort of individuals affected by
      language impairment. METHODS: We perform quantitative association analyses of
      three linguistic measures and case-control association analyses using both SNP
      data and imputed HLA types. RESULTS: Quantitative association analyses of imputed
      HLA types suggested a role for the HLA-A locus in susceptibility to SLI. HLA-A A1
      was associated with a measure of short-term memory (P = 0.004) and A3 with
      expressive language ability (P = 0.006). Parent-of-origin effects were found
      between HLA-B B8 and HLA-DQA1*0501 and receptive language. These alleles have a
      negative correlation with receptive language ability when inherited from the
      mother (P = 0.021, P = 0.034, respectively) but are positively correlated with
      the same trait when paternally inherited (P = 0.013, P = 0.029, respectively).
      Finally, case control analyses using imputed HLA types indicated that the DR10
      allele of HLA-DRB1 was more frequent in individuals with SLI than population
      controls (P = 0.004, relative risk = 2.575), as has been reported for individuals
      with attention deficit hyperactivity disorder (ADHD). CONCLUSION: These
      preliminary data provide an intriguing link to those described by previous
      studies of other neurodevelopmental disorders and suggest a possible role for HLA
      loci in language disorders.

PMID- 24433327
TI  - Relations between maternal interactive behavior and mastery motivation in
      children with developmental disabilities.

PMID- 24433329
TI  - Infantile case of eosinophilic pustular folliculitis successfully treated with
      topical indomethacin.

PMID- 24433328
TI  - Tryptase is a candidate autoantigen in rheumatoid arthritis.
AB  - Autoimmune processes have been implicated in the development of rheumatoid
      arthritis (RA); however, specific autoantigens that play a role in the aetiology
      of RA have been lacking. In this study, we found that sera from RA patients were
      particularly immunoreactive against the protein tryptase. Compared with
      osteoarthritis (OA) patients and healthy controls, RA patients had relatively
      higher levels of tryptase and concomitant anti-tryptase antibodies in their
      synovial tissues and sera. Similarly, synovial fluid from RA patients, but not
      from OA patients, contained antibodies that recognized tryptase in vitro. In
      addition, serum tryptase levels in both early and late RA patients significantly
      correlated with clinical indices usually used to diagnose RA, such as rheumatoid
      factor, Disease Activity Score using 28 joint counts and autoantibodies against
      cyclic citrullinated peptide. Our results identify tryptase as a candidate
      autoantigen involved in the pathogenesis of RA and monitoring its levels may have
      diagnostic and prognostic value. 

PMID- 24433330
TI  - Exploration of plant growth and development using the European Modular
      Cultivation System facility on the International Space Station.
AB  - Space experiments provide a unique opportunity to advance our knowledge of how
      plants respond to the space environment, and specifically to the absence of
      gravity. The European Modular Cultivation System (EMCS) has been designed as a
      dedicated facility to improve and standardise plant growth in the International
      Space Station (ISS). The EMCS is equipped with two centrifuges to perform
      experiments in microgravity and with variable gravity levels up to 2.0 g. Seven
      experiments have been performed since the EMCS was operational on the ISS. The
      objectives of these experiments aimed to elucidate phototropic responses
      (experiments TROPI-1 and -2), root gravitropic sensing (GRAVI-1), circumnutation
      (MULTIGEN-1), cell wall dynamics and gravity resistance (Cell wall/Resist wall),
      proteomic identification of signalling players (GENARA-A) and mechanism of InsP3
      signalling (Plant signalling). The role of light in cell proliferation and plant
      development in the absence of gravity is being analysed in an on-going experiment
      (Seedling growth). Based on the lessons learned from the acquired experience,
      three preselected ISS experiments have been merged and implemented as a single
      project (Plant development) to study early phases of seedling development. A
      Topical Team initiated by European Space Agency (ESA), involving experienced
      scientists on Arabidopsis space research experiments, aims at establishing a
      coordinated, long-term scientific strategy to understand the role of gravity in
      Arabidopsis growth and development using already existing or planned new
      hardware.

PMID- 24433331
TI  - A comparison of thoracolumbar intervertebral disc extrusion in French Bulldogs
      and Dachshunds and association with congenital vertebral anomalies.
AB  - OBJECTIVES: To compare data for French Bulldogs and Dachshunds that had
      hemilaminectomy for thoracolumbar intervertebral disc extrusion (T-L IVDE) by 1
      surgeon and to evaluate the association between IVDE and congenital vertebral
      anomalies. DESIGN: Retrospective case series. ANIMALS: French Bulldogs (n = 47)
      and 671 Dachshunds. METHODS: Age, gender, vertebral anomaly,
      kyphosis/kyphoscoliosis, IVDE site, non-recovery and progressive hemorrhagic
      myelomalacia development from grade 5 (paraplegia without deep nociception) were
      compared between the 2 breeds. RESULTS: French Bulldogs were significantly
      younger (P = .00001), more likely to be male (P = .023), and more likely to have
      a congenital vertebral anomaly and kyphosis/kyphoscoliosis (P < .00001) than
      Dachshunds. The frequencies of French Bulldogs with IVDE within typical sites
      (T11-L3) were significantly lower (P = .0005) and within caudal sites (L3-L7)
      significantly higher (P = .0001) compared with Dachshunds. None of the French
      Bulldogs had IVDE within the kyphotic/kyphoscoliotic segment. The frequency of
      lumbar IVDE (L1-L5) in French Bulldogs with kyphosis/kyphoscoliosis was
      significantly higher (P = .003) compared with French Bulldogs without
      kyphosis/kyphoscoliosis. In grade 5 dogs, the risk of developing progressive
      hemorrhagic myelomalacia in French Bulldogs was significantly higher (P = .03)
      than in Dachshunds. CONCLUSION: The distribution of IVDE site in French Bulldogs
      within the thoracolumbar and lumbar spine was different from Dachshunds. IVDE
      sites were not located at the sites of vertebral anomaly. French Bulldogs
      appeared to have T-L IVDE at younger ages, with higher male predisposition and
      higher risk of developing progressive hemorrhagic myelomalacia from grade 5
      compared with Dachshunds.

PMID- 24433332
TI  - An experimental model to investigate the targeting accuracy of MR-guided focused
      ultrasound ablation in liver.
AB  - BACKGROUND: Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU)
      is a hybrid technology that aims to offer non-invasive thermal ablation of
      targeted tumors or other pathological tissues. Acoustic aberrations and non
      linear wave propagating effects may shift the focal point significantly away from
      the prescribed (or, theoretical) position. It is therefore mandatory to evaluate
      the spatial accuracy of ablation for a given HIFU protocol and/or device. We
      describe here a method for producing a user-defined ballistic target as an
      absolute reference marker for MRgHIFU ablations. METHODS: The investigated method
      is based on trapping a mixture of MR contrast agent and histology stain using
      radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF
      electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15
      seconds) and injection of the mixture followed by a second RF coagulation. As a
      result, the contrast agent/stain is encapsulated in the intercellular space.
      Ultrasonography imaging was performed during the procedure, while high resolution
      T1w 3D VIBE MR acquisition was used right after to identify the position of the
      ballistic marker and hence the target tissue. For some cases, after the marker
      fixation procedure, HIFU volumetric ablations were produced by a phased-array
      HIFU platform. First ex vivo experiments were followed by in vivo investigation
      on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7.
      RESULTS: At the end of the procedure, no ultrasound indication of the marker's
      presence could be observed, while it was clearly visible under MR and could be
      conveniently used to prescribe the HIFU ablation, centered on the so-created
      target. The marker was identified at Day 7 after treatment, immediately after
      animal sacrifice, after 3 weeks of post-mortem formalin fixation and during
      histology analysis. Its size ranged between 2.5 and 4 mm. CONCLUSIONS:
      Experimental validation of this new ballistic marker method was performed for
      liver MRgHIFU ablation, free of any side effects (e.g. no edema around the
      marker, no infection, no bleeding). The study suggests that the absolute
      reference marker had ultrasound conspicuity below the detection threshold, was
      irreversible, MR-compatible and MR-detectable, while also being a well
      established histology staining technique.

PMID- 24433333
TI  - Quality pain management in the hospital setting from the patient's perspective.
AB  - BACKGROUND: Pain management is a crucial issue for patients, and patients'
      perception of care is an important quality outcome criterion for health care
      institutions. Pain remains a common problem in hospitals, with subsequent
      deleterious effects on well-being. OBJECTIVES: To assess the epidemiology of pain
      (frequency, severity, and interference), patient participation in pain treatment
      decisions, and patient satisfaction with care in a hospital setting. METHODS: A
      point-prevalence study was conducted. Data were collected with the American Pain
      Society Patient Outcome Questionnaire (Icelandic version). Participants (n = 308)
      were >= 18 years old, alert, and hospitalized for >= 24 hours. RESULTS: The
      response rate was 73%. The mean age of participants was 67.5 (SD = 17.4; range 18
      to 100) years, and 49% were men. Pain prevalence in the past 24 hours was 83%,
      mean worst pain severity was 4.6 (SD = 3.1), and 35% experienced severe pain (>=
      7 on 0 to 10 scale). Moderate to severe interference with activities and sleep
      was experienced by 36% and 29% of patients respectively. Patient participation in
      decision making was weakly associated with spending less time in severe pain and
      better pain relief. Patient satisfaction was related to spending less time in
      severe pain, better pain relief, and lower pain severity (P < 0.05). CONCLUSIONS:
      Pain was both prevalent and severe in the hospital, but patient participation in
      decision making was related to better outcomes. Optimal pain management, with
      emphasis on patient participation in decision making, should be encouraged in an
      effort to improve the quality of care in hospitals.

PMID- 24433334
TI  - Control of pili and sialyltransferase expression in Neisseria gonorrhoeae is
      mediated by the transcriptional regulator CrgA.
AB  - Contact-regulated gene A (CrgA) is a transcriptional regulator present in the
      pathogenic Neisseria that functions as both an activator and a repressor of
      transcription following contact with host cells. While its mechanism of action
      has been studied extensively in Neisseria meningitidis, the specific subset of
      genes that CrgA targets has been debated. Although the majority of these
      constitute virulence genes, suggesting that CrgA is important in pathogenesis, no
      study to date has examined the effects of CrgA in Neisseria gonorrhoeae. In this
      report, we generated a knockout mutant of crgA (DeltacrgA) in the serum-sensitive
      gonococcal strain F62. crgA deletion resulted in a reduction in the transcript
      and protein levels of the primary pilin component pilE via mechanisms that were
      both contact-dependent and -independent. In contrast, DeltacrgA overexpressed the
      main determinant of serum resistance in F62, lipooligosaccharide
      sialyltransferase (Lst). CrgA-mediated lst repression was direct as both
      recombinant and native CrgA bound to the lst promoter at multiple locations in
      EMSA and ChIP assays respectively. The increase in Lst levels associated with
      crgA deletion correlated with enhanced protection against killing by normal human
      serum. These data suggest a role for CrgA in virulence regulation during both
      cell adherence and planktonic growth. 

PMID- 24433335
TI  - Reply: To PMID 24004162.

PMID- 24433336
TI  - Excess adiposity and survival in patients with colorectal cancer: a systematic
      review.
AB  - Excess adiposity is an established risk factor for incident colorectal cancer
      (CRC) but whether this association extrapolates to poorer survival is unclear. We
      undertook a systematic review to examine relationships between measures of
      adiposity and survival in patients with CRC. For distinction, we included pre
      diagnosis exposure and CRC-related mortality. We performed dose-response meta
      analyses and assessed study quality using eight domains of bias. Six study
      categories were identified based on (i) timing of adiposity measurement relative
      to survival analysis time zero and (ii) clinical setting. Several types of
      adiposity measurements were reported; body mass index (BMI) was the commonest.
      For pre-diagnosis cohorts, baseline BMI negatively impacted on CRC-related
      mortality in men only (risk estimate per 5 kg m(-2)  = 1.19, 95% confidence
      intervals: 1.14-1.25). The other groups were pre-diagnosis BMI but diagnosis as
      time zero; population-based cohorts; treatment cohorts; observational analyses
      within adjuvant chemotherapy trials; patients with metastatic CRC - each had
      several biases (e.g. treatment selection, reverse causality) and sources of
      confounding (e.g. chemotherapy 'capping'). Overall, there was insufficient
      evidence for a strong link between adiposity and survival. These findings
      demonstrate an important principle: an established link between an exposure
      (here, adiposity) and increased cancer incidence does not necessarily extrapolate
      into an inferior post-treatment outcome. 

PMID- 24433337
TI  - Variation in thromboxane B2 concentrations in serum and plasma in patients taking
      regular aspirin before and after clopidogrel therapy.
AB  - Dual antiplatelet therapy with aspirin and a P2Y12 antagonist is widely
      prescribed for the prevention of thrombotic events in patients with an acute
      coronary syndrome or undergoing percutaneous coronary intervention (PCI). It is
      recognised that there is inter-individual variation in the antiplatelet effects
      of both drugs. Recent data also suggest that P2Y12 antagonists can affect the
      response to aspirin. A direct indicator of the effect of aspirin on platelets is
      their ability to generate thromboxane, which if measured as the difference
      between the level of thromboxane B2 in serum and plasma ([TxB2]S-P) avoids the
      confounding effect of endogenous TxB2 production from other cells. We therefore
      analysed [TxB2]S-P as a measure of aspirin response in a group of 123 patients
      undergoing elective PCI before and after the introduction of clopidogrel. In a
      subgroup of 40 patients taking aspirin alone, we compared [TxB2]S-P and VerifyNow
      Aspirin for the assessment of aspirin response. There was a wide variation in
      plasma and serum TxB2 concentrations both before and after clopidogrel therapy
      but only 3.5% of patients had residual serum concentration of TxB2 > 10 ng/ml.
      There was a strong correlation between the pre and post clopidogrel levels of
      TxB2 (r >= 0.78; p = 0.001) and no significant difference in [TxB2]S-P. There was
      no correlation between the magnitude of response to clopidogrel response and the
      generation of thromboxane B2. Correlation between [TxB2]S-P and VerifyNow Aspirin
      was poor. We conclude that the use of a P2Y12 antagonist does not influence the
      effect of aspirin on the ability of platelets to generate thromboxane. Therefore,
      measurement of TxB2 levels in serum, after subtracting the contribution from
      plasma, provides a measure of the response to aspirin in patients taking dual
      antiplatelet therapy.

PMID- 24433338
TI  - A new frontier in haematology - combining pharmacokinetic with pharmacodynamic
      factors to improve choice and dose of drug.
AB  - The issue of tailored dosing adjusted according to a range of patient-specific
      factors other than bodyweight or body surface area is of large and increasing
      clinical and financial concern. Even if it is known that dosing alterations are
      likely to be required for parameters such as body composition, gender and
      pharmacogenetics, the amount of dosing change is unknown. Thus,
      pharmacokinetically guided dosing is making a resurgence, particularly in areas
      of medicine where there are cost constraints or safety issues, such as in
      haematology medications. However, the evidence to support the behaviour is
      minimal, particularly when long-term outcomes are considered. In haematology,
      there are particular issues around efficacy, toxicity and overall cost. Newer
      targeted agents, such as the monoclonal antibody rituximab and the tyrosine
      kinase inhibitor imatinib, whilst clearly being highly effective, are dosed on a
      milligram per square metre (rituximab) or fixed dose basis (imatinib), regardless
      of body composition, tumour aspects or comorbidity. This review questions this
      practice and raises important clinical issues; specifically, the clinical
      potential for combined pharmacokinetically and pharmacodynamically guided dosing
      of new targeted agents in haematological malignancies. This pharmacokinetically
      and pharmacodynamically guided dosing is an emerging area of clinical
      pharmacology, driven predominantly by toxicity, efficacy and cost issues, but
      also because reasonable outcomes are being noted with more appropriately dosed
      older medications adjusted for patient-specific factors. Clinical trials to
      investigate the optimization of rituximab dose scheduling are required. 

PMID- 24433339
TI  - Dobutamine stress echocardiography for assessment of systolic function in dogs
      with experimentally induced mitral regurgitation.
AB  - BACKGROUND: Systolic dysfunction is associated with poor outcomes in dogs with
      myxomatous mitral valve disease. However, assessment of systolic variables by
      conventional echocardiographic methods is difficult in these dogs because of
      mitral regurgitation (MR). HYPOTHESIS: We hypothesized that assessment of
      systolic function by dobutamine stress may identify systolic dysfunction in dogs
      with MR, and that 2-dimensional speckle-tracking echocardiography (2D-STE) could
      quantitatively evaluate myocardial function. ANIMALS: Anesthetized dogs with
      experimentally induced MR. METHODS: Dogs were examined for systolic myocardial
      deformations using 2D-STE during dobutamine infusion before and 3 and 6 months
      after MR induction. We evaluated peak systolic rotation and rotation rate in each
      basal and apical view; peak systolic torsion and torsion rate were also
      calculated. RESULTS: Invasive peak positive first derivatives of left ventricular
      pressure (dp/dt) were significantly decreased in dogs 6 months after induction of
      MR compared with pre-MR results. After 3 and 6 months of MR, dogs had diminished
      peak systolic torsion values and torsion rates in response to dobutamine infusion
      compared with pre-MR results (3 months, P < .001 and P = .006; 6 months, P = .003
      and P = .021). These results were significantly correlated with overall invasive
      dp/dt (r = 0.644, P < .001; r = 0.696, P < .001). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Decreased torsion during dobutamine infusion in dogs with MR may
      reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be
      useful for the assessment of systolic function in dogs with MR.

PMID- 24433340
TI  - Family caregivers' assessments of caring for a relative with dementia: a
      comparison of urban and rural areas.
AB  - AIM: This study aimed to describe and compare urban and rural family caregivers'
      reactions to caring for a relative with dementia and to examine the associations
      between caregiving and socio-demographic factors. BACKGROUND: Most studies on
      family caregivers' experiences caring for older people with dementia have been
      conducted in urban areas, and little is known about the experiences of family
      caregivers living in rural areas. DESIGN: A cross-sectional study design was
      used. METHODS: A total of 102 caregivers (response rate 85%) from urban (n=57)
      and rural (n=46) areas completed the Caregiver Reaction Assessment (CRA) Scale
      and demographic information. Data were analysed using descriptive and inferential
      statistics and linear regression models. RESULTS: Overall, family caregivers
      reported high satisfaction even if they also reported high impact on finances and
      daily living. Rural caregivers experienced a higher negative impact on finances
      but reported more support from family members than urban caregivers. Age, gender
      and relationship were significantly associated with four of the five CRA
      subscales. Educational level and geographical setting were not associated with
      any of the CRA subscales. CONCLUSIONS: The results of the study raise questions
      about the financial situation of older female caregivers and on the expectations
      of built-in family structures in urban and rural areas. Further studies focusing
      on the meaning and constitution of a family would help us to understand how these
      factors influence family caregiving both in rural and urban areas. IMPLICATIONS
      FOR PRACTICE: To provide person-centred care and to avoid stereotyped caregiving,
      a better picture of traditions in family caregiving can improve a more
      differentiated and appropriate professional caregiving pliable with the cultural
      context in which it is carried out.

PMID- 24433344
TI  - Oculomotor assessment and cognitive functions in children after traumatic brain
      injury.

PMID- 24433341
TI  - Sambucus nigra extracts inhibit infectious bronchitis virus at an early point
      during replication.
AB  - BACKGROUND: Infectious bronchitis virus (IBV) is a pathogenic chicken
      coronavirus. Currently, vaccination against IBV is only partially protective;
      therefore, better preventions and treatments are needed. Plants produce
      antimicrobial secondary compounds, which may be a source for novel anti-viral
      drugs. Non-cytotoxic, crude ethanol extracts of Rhodiola rosea roots, Nigella
      sativa seeds, and Sambucus nigra fruit were tested for anti-IBV activity, since
      these safe, widely used plant tissues contain polyphenol derivatives that inhibit
      other viruses. RESULTS: Dose-response cytotoxicity curves on Vero cells using
      trypan blue staining determined the highest non-cytotoxic concentrations of each
      plant extract. To screen for IBV inhibition, cells and virus were pretreated with
      extracts, followed by infection in the presence of extract. Viral cytopathic
      effect was assessed visually following an additional 24 h incubation with
      extract. Cells and supernatants were harvested separately and virus titers were
      quantified by plaque assay. Variations of this screening protocol determined the
      effects of a number of shortened S. nigra extract treatments. Finally, S. nigra
      extract-treated virions were visualized by transmission electron microscopy with
      negative staining.Virus titers from infected cells treated with R. rosea and N.
      sativa extracts were not substantially different from infected cells treated with
      solvent alone. However, treatment with S. nigra extracts reduced virus titers by
      four orders of magnitude at a multiplicity of infection (MOI) of 1 in a dose
      responsive manner. Infection at a low MOI reduced viral titers by six orders of
      magnitude and pretreatment of virus was necessary, but not sufficient, for full
      virus inhibition. Electron microscopy of virions treated with S. nigra extract
      showed compromised envelopes and the presence of membrane vesicles, which
      suggested a mechanism of action. CONCLUSIONS: These results demonstrate that S.
      nigra extract can inhibit IBV at an early point in infection, probably by
      rendering the virus non-infectious. They also suggest that future studies using
      S. nigra extract to treat or prevent IBV or other coronaviruses are warranted.

PMID- 24433342
TI  - Morphological changes of cortical pyramidal neurons in hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome
      associated with acute and chronic liver diseases. It includes a number of
      neuropsychiatric disturbances including impaired motor activity and coordination,
      intellectual and cognitive function. RESULTS: In the present study, we used a
      chronic rat HE model by ligation of the bile duct (BDL) for 4 weeks. These rats
      showed increased plasma ammonia level, bile duct hyperplasia and impaired spatial
      learning memory and motor coordination when tested with Rota-rod and Morris water
      maze tests, respectively. By immunohistochemistry, the cerebral cortex showed
      swelling of astrocytes and microglia activation. To gain a better understanding
      of the effect of HE on the brain, the dendritic arbors of layer V cortical
      pyramidal neurons and hippocampal CA1 pyramidal neurons were revealed by an
      intracellular dye injection combined with a 3-dimensional reconstruction.
      Although the dendritic arbors remained unaltered, the dendritic spine density on
      these neurons was significantly reduced. It was suggested that the reduction of
      dendritic spines may be the underlying cause for increased motor evoked potential
      threshold and prolonged central motor conduction time in clinical finding in
      cirrhosis. CONCLUSIONS: We found that HE perturbs CNS functions by altering the
      dendritic morphology of cortical and hippocampal pyramidal neurons, which may be
      the underlying cause for the motor and intellectual impairments associated with
      HE patients.

PMID- 24433345
TI  - Prevalence of disc displacement of various severities among young preorthodontic
      population: a magnetic resonance imaging study.
AB  - PURPOSE: There has been no study on the prevalence of disc displacement (DD) of
      different levels in children and adolescents with adequate sample size using
      magnetic resonance images (MRIs). This retrospective cross-sectional study was
      designed to investigate the relationship between increasing age and the
      prevalence of DD of various severities in a young preorthodontic population.
      MATERIALS AND METHODS: Of 199 preorthodontic patients aged 6 to 15 years visiting
      a private orthodontic office for initial examination, 153 patients with signs and
      symptoms of temporomandibular joint (TMJ) disorders had MRIs of their TMJs taken
      for further evaluation. Of those, 302 TMJs from 151 patients' MRIs of diagnostic
      quality were divided into three age groups (I: 6 to 9, II: 10 to 12, and III: 13
      to 15 years). DD of each patient was categorized based on its severity from stage
      0 (normal) to stage 4 (total DD without reduction). The distribution of DD stages
      in each age group was plotted on a line graph and statistically analyzed for
      intergroup comparison. RESULTS: A graphical representation of the results clearly
      demonstrated a trend for higher occurrence of more advanced DD with an increase
      in age. No gender difference was observed. Statistical analysis showed that DD
      was significantly more advanced in group II than group I (p < 0.01) and group III
      than group I (p < 0.01). CONCLUSIONS: The study revealed a high prevalence of DD
      in the young preorthodontic population and significant increase in the proportion
      of patients with more advanced stages of DD in older patients.

PMID- 24433346
TI  - Effect size and cost-effectiveness estimates of breast and cervical cancer
      screening reminders by population size through complete enumeration of Japanese
      local municipalities.
AB  - BACKGROUND: Client reminders are known to increase cancer screening attendance
      rates. However, there are significant costs associated with them, and their
      effect by population size is unknown. METHODS: In 2007 and 2008, the Japanese
      Government surveyed breast and cervical cancer screening in every municipality in
      Japan. From the results, we selected all 1,464 municipalities that carried out
      both screening types. We examined whether changes in screening attendance rates
      between 2007 and 2008 were associated with client reminders, number of public
      health nurses per 100,000 population, financial strength index, and 2007
      attendance rates for different population sizes. We then calculated cost
      effectiveness estimates of client reminders by population size and screening
      type. RESULTS: Client reminders were associated with increased attendance rates
      in populations <100,000. For populations of 50,000-100,000, there was a 2.76%
      increase in breast cancer screening (95% CI: 0.41, 5.11), and a 2.25% increase in
      cervical cancer screening (95% CI: 0.89, 3.61). The incremental cost per
      additional attendance was higher in populations <50,000 than in populations of
      50,000-100,000 (breast, $100 versus $54; cervical, $149 versus $67 respectively).
      CONCLUSIONS: Client reminders for breast and cervical cancer screening increased
      attendance rates in smaller municipalities in Japan.

PMID- 24433347
TI  - Increased numbers and functional activity of CD56+ T cells in healthy
      cytomegalovirus positive subjects.
AB  - Human T cells expressing CD56 are capable of tumour cell lysis following
      activation with interleukin-2 but their role in viral immunity has been less well
      studied. Proportions of CD56(+) T cells were found to be highly significantly
      increased in cytomegalovirus-seropositive (CMV(+) ) compared with seronegative
      (CMV(-) ) healthy subjects (9.1 +/- 1.5% versus 3.7 +/- 1.0%; P < 0.0001).
      Proportions of CD56(+) T cells expressing CD28, CD62L, CD127, CD161 and CCR7 were
      significantly lower in CMV(+) than CMV(-) subjects but those expressing CD4, CD8,
      CD45RO, CD57, CD58, CD94 and NKG2C were significantly increased (P < 0.05), some
      having the phenotype of T effector memory cells. Levels of pro-inflammatory
      cytokines and CD107a were significantly higher in CD56(+) T cells from CMV(+)
      than CMV(-) subjects following stimulation with CMV antigens. This also resulted
      in higher levels of proliferation in CD56(+) T cells from CMV(+) than CMV(-)
      subjects. Using Class I HLA pentamers, it was found that CD56(+) T cells from
      CMV(+) subjects contained similar proportions of antigen-specific CD8(+) T cells
      to CD56(-) T cells in donors of several different HLA types. These differences
      may reflect the expansion and enhanced functional activity of CMV-specific
      CD56(+) memory T cells. In view of the link between CD56 expression and T-cell
      cytotoxic function, this strongly implicates CD56(+) T cells as being an
      important component of the cytotoxic T-cell response to CMV in healthy carriers.

PMID- 24433349
TI  - Perifollicular elastolysis with atopic dermatitis.

PMID- 24433348
TI  - Short message service (SMS) interventions for the prevention and treatment of
      sexually transmitted infections: a systematic review protocol.
AB  - BACKGROUND: Globally, the incidence of sexually transmitted infections (STI) is
      rising, posing a challenge to its control and appropriate management. Text
      messaging has become the most common mode of communication among almost six
      billion mobile phone users worldwide. Text messaging can be used to remind
      patients about clinic appointments, to notify patients that it is time for STI re
      testing, and to facilitate patient communication with their health professionals
      with any questions and concerns they may have about their sexual health. While
      there are a handful of systematic reviews published on short message service
      (SMS) interventions in a variety of health settings and issues, none are related
      to sexual health. We plan to conduct a systematic review to examine the impact
      text messaging might have on interventions for the prevention and care of
      patients with STIs. METHODS/DESIGN: Eligible studies will include both
      quantitative and qualitative studies published after 1995 that discuss the
      efficacy and effectiveness of SMS interventions for STI prevention and management
      using text messaging. Data will be abstracted independently by two reviewers
      using a standardized pre-tested data abstraction form. Inter-rater reliability
      scores will be obtained to ensure consistency in the inclusion and data
      extraction of studies. Heterogeneity will be assessed using the I2 test and
      subgroup analyses. A nonhypothesis driven inductive reasoning approach as well as
      a coding framework will be applied to analyze qualitative studies. A meta
      analysis may be conducted if sufficient quantitative studies are found using
      similar outcomes. DISCUSSION: For this protocol, we identified ten related
      systematic reviews. The reviews were limited to a particular disease or setting,
      were not exclusive to SMS interventions, or were out of date. This systematic
      review will be the first comprehensive examination of studies that discuss the
      effectiveness of SMS on multiple outcomes that relate to STI prevention and
      management, covering diverse settings and populations. Findings of the systematic
      review and any additional meta-analyses will be published and presented to our
      key knowledge users. This information will provide the evidence that is required
      to appropriately adopt text messaging into standard practice in STI care.

PMID- 24433350
TI  - Case-mix and quality indicators in Chinese elder care homes: are there
      differences between government-owned and private-sector facilities?
AB  - OBJECTIVES: To assess the association between ownership of Chinese elder care
      facilities and their performance quality and to compare the case-mix profile of
      residents and facility characteristics in government-owned and private-sector
      homes. DESIGN: Cross-sectional study. SETTING: Census of elder care homes
      surveyed in Nanjing (2009) and Tianjin (2010). PARTICIPANTS: Elder care
      facilities located in urban Nanjing (n = 140, 95% of all) and urban Tianjin (n =
      157, 97% of all). MEASUREMENTS: A summary case-mix index based on activity of
      daily living (ADL) limitations and cognitive impairment was created to measure
      levels of care needs of residents in each facility. Structure, process, and
      outcome measures were selected to assess facility-level quality of care. A
      structural quality measure, understaffing relative to resident levels of care
      needs, which indicates potentially inadequate staffing given resident case-mix,
      was also developed. RESULTS: Government-owned homes had significantly higher
      occupancy rates, presumably reflecting popular demand for publicly subsidized
      beds, but served residents who, on average, have fewer ADL and cognitive
      functioning limitations than those in private-sector facilities. Across a range
      of structure, process, and outcome measures of quality, there is no clear
      evidence suggesting advantages or disadvantages of either ownership type,
      although when staffing-to-resident ratio is gauged relative to resident case-mix,
      private-sector facilities were more likely to be understaffed than government
      owned facilities. CONCLUSION: In Nanjing and Tianjin, private-sector homes were
      more likely to be understaffed, although their residents were sicker and frailer
      on average than those in government facilities. It is likely that the case-mix
      differences are the result of selective admission policies that favor healthier
      residents in government facilities than in private-sector homes.

PMID- 24433352
TI  - Gene testing for the next generation.

PMID- 24433351
TI  - Novel anti-glioblastoma agents and therapeutic combinations identified from a
      collection of FDA approved drugs.
AB  - BACKGROUND: Glioblastoma (GBM) is a therapeutic challenge, associated with high
      mortality. More effective GBM therapeutic options are urgently needed. Hence, we
      screened a large multi-class drug panel comprising the NIH clinical collection
      (NCC) that includes 446 FDA-approved drugs, with the goal of identifying new GBM
      therapeutics for rapid entry into clinical trials for GBM. METHODS: Screens using
      human GBM cell lines revealed 22 drugs with potent anti-GBM activity, including
      serotonergic blockers, cholesterol-lowering agents (statins), antineoplastics,
      anti-infective, anti-inflammatories, and hormonal modulators. We tested the 8
      most potent drugs using patient-derived GBM cancer stem cell-like lines. Notably,
      the statins were active in vitro; they inhibited GBM cell proliferation and
      induced cellular autophagy. Moreover, the statins enhanced, by 40-70 fold, the
      pro-apoptotic activity of irinotecan, a topoisomerase 1 inhibitor currently used
      to treat a variety of cancers including GBM. Our data suggest that the mechanism
      of action of statins was prevention of multi-drug resistance protein MDR-1
      glycosylation. This drug combination was synergistic in inhibiting tumor growth
      in vivo. Compared to animals treated with high dose irinotecan, the drug
      combination showed significantly less toxicity. RESULTS: Our data identifies a
      novel combination from among FDA-approved drugs. In addition, this combination is
      safer and well tolerated compared to single agent irinotecan. CONCLUSIONS: Our
      study newly identifies several FDA-approved compounds that may potentially be
      useful in GBM treatment. Our findings provide the basis for the rational
      combination of statins and topoisomerase inhibitors in GBM.

PMID- 24433353
TI  - Genomic landscape of retinoblastoma.

PMID- 24433354
TI  - Corneal dystrophies and genetics in the International Committee for
      Classification of Corneal Dystrophies era: a review.
AB  - Many of the corneal dystrophies have now been genetically characterized, and a
      system was established in 2008 by The International Committee for Classification
      of Corneal Dystrophies (IC3D) in an attempt to standardize the nomenclature. IC3D
      provided a classification system whereby all dystrophies can be categorized on
      the basis of the underlying genetic knowledge. Since that time, further work has
      established even more phenotypic and allelic heterogeneity than anticipated,
      particular for Fuchs endothelial corneal dystrophy and posterior polymorphous
      dystrophy. Using genome-wide association studies, a number of genes are now
      implicated both in normal corneal quantitative traits, such as central corneal
      thickness, as well as in disease. There is also a trend towards functional
      characterization of the genetic variants involved to elucidate the
      pathophysiology of these entities. This review article will provide an overview
      of the knowledge to date, with an emphasis on findings since the IC3D
      classification was published in 2008. 

PMID- 24433355
TI  - Genomics and anterior segment dysgenesis: a review.
AB  - Anterior segment dysgenesis refers to a spectrum of disorders affecting
      structures in the anterior segment of the eye including the iris, cornea and
      trabecular meshwork. Approximately 50% of patients with anterior segment
      dysgenesis develop glaucoma. Traditional genetic methods using linkage analysis
      and family-based studies have identified numerous disease-causing genes such as
      PAX6, FOXC1 and PITX2. Despite these advances, phenotypic and genotypic
      heterogeneity pose continuing challenges to understand the mechanisms underlying
      the complexity of anterior segment dysgenesis disorders. Genomic methods, such as
      genome-wide association studies, are potentially an effective tool to understand
      anterior segment dysgenesis and the individual susceptibility to the development
      of glaucoma. In this review, we provide the rationale, as well as the challenges,
      to utilizing genomic methods to examine anterior segment dysgenesis disorders. 

PMID- 24433357
TI  - Translating the ENCyclopedia Of DNA Elements Project findings to the clinic:
      ENCODE's implications for eye disease.
AB  - Approximately 10 years after the Human Genome Project unravelled the sequence of
      our DNA, the ENCyclopedia Of DNA Elements (ENCODE) Project sought to interpret
      it. Data from the recently completed project have shed new light on the
      proportion of biologically active human DNA, assigning a biochemical role to much
      of the sequence previously considered to be 'junk'. Many of these newly
      catalogued functional elements represent epigenetic mechanisms involved in
      regulation of gene expression. Analogous to an Ishihara plate, a gene-coding
      region of DNA (target dots) only comes into context when the non-coding DNA
      (surrounding dots) is appreciated. In this review we provide an overview of the
      ENCODE project, discussing the significance of these data for ophthalmic research
      and eye disease. The novel insights afforded by the ENCODE project will in time
      allow for the development of new therapeutic strategies in the management of
      common blinding disorders. 

PMID- 24433358
TI  - Total cystectomy for treatment of transitional cell carcinoma of the urethra and
      bladder trigone in a dog.
AB  - OBJECTIVE: To report total cystectomy with reimplantation of the ureters in the
      proximal aspect of the vagina. STUDY DESIGN: Case report. ANIMALS: An 11-year-old
      female spayed Vizsla with spontaneously occurring transitional cell carcinoma of
      the urethra and bladder. METHODS: After initial treatment for transitional cell
      carcinoma of the bladder trigone with urethral stent placement and chemotherapy,
      the dog developed urinary incontinence 2 months after stent placement. Eleven
      months after initial diagnosis, the dog developed pulmonary metastasis and local
      progression, leading to bilateral ureteral dilatation. After palliative
      radiation, total cystectomy was performed. RESULTS: The owners elected euthanasia
      442 days after original presentation and 92 days after total cystectomy.
      Euthanasia was unrelated to the surgical procedure, but was related to the
      primary disease. CONCLUSIONS: Total cystectomy is a technically feasible
      procedure that should be considered for the treatment of bladder cancer in dogs.

PMID- 24433356
TI  - The genomic landscape of retinoblastoma: a review.
AB  - Retinoblastoma is a paediatric ocular tumour that continues to reveal much about
      the genetic basis of cancer development. Study of genomic aberrations in
      retinoblastoma tumours has exposed important mechanisms of cancer development and
      identified oncogenes and tumour suppressors that offer potential points of
      therapeutic intervention. The recent development of next-generation genomic
      technologies has allowed further refinement of the genomic landscape of
      retinoblastoma at high resolution. In a relatively short period of time, a wealth
      of genetic and epigenetic data has emerged on a small number of tumour samples.
      These data highlight the inherent molecular complexity of this cancer despite the
      fact that most retinoblastomas are initiated by the inactivation of a single
      tumour suppressor gene. This review outlines the current understanding of the
      genomic, genetic and epigenetic changes in retinoblastoma, highlighting recent
      genome-wide analyses that have identified exciting candidate genes worthy of
      further validation as potential prognostic and therapeutic targets. 

PMID- 24433359
TI  - A systematic review of persuasive marketing techniques to promote food to
      children on television.
AB  - The ubiquitous marketing of energy-dense, nutrient-poor food and beverages is a
      key modifiable influence on childhood dietary patterns and obesity. Much of the
      research on television food advertising is focused on identifying and quantifying
      unhealthy food marketing with comparatively few studies examining persuasive
      marketing techniques to promote unhealthy food to children. This review
      identifies the most frequently documented persuasive marketing techniques to
      promote food to children via television. A systematic search of eight online
      databases using key search terms identified 267 unique articles. Thirty-eight
      articles met the inclusion criteria. A narrative synthesis of the reviewed
      studies revealed the most commonly reported persuasive techniques used on
      television to promote food to children. These were the use of premium offers,
      promotional characters, nutrition and health-related claims, the theme of taste,
      and the emotional appeal of fun. Identifying and documenting these commonly
      reported persuasive marketing techniques to promote food to children on
      television is critical for the monitoring and evaluation of advertising codes and
      industry pledges and the development of further regulation in this area. This has
      a strong potential to curbing the international obesity epidemic besieging
      children throughout the world. 

PMID- 24433360
TI  - Unintentional cervical dural tap treated with lumbar blood patch.
AB  - Cervical radicular pain presents itself as pain radiating from the neck to the
      arm. If conservative treatment fails, a cervical epidural steroid injection can
      be considered. A rare but possible complication resulting from the interlaminar
      approach is unintentional cervical dural puncture that may result in post-dural
      puncture headache (PDPH). Dural puncture from an interlaminar cervical epidural
      injection reportedly range from 0.25% to 2.65%. An epidural blood patch is a
      possible treatment option when conservative treatment fails. Relief could be
      secondary to 'sealing' of the dural tear from the clotted blood and
      reestablishment of physiological intracranial pressure. Another theory is an
      increase in the subarachnoid pressure from the injected blood. The increased
      pressure may restore normal intracranial pressure. We describe 2 cases of
      cervical PDPH treated with lumbar epidural blood patch. In 1 case, there was
      complete resolution of the symptoms and in the other case, there was great
      improvement of symptoms and a high thoracic blood patch was performed to resolve
      the remaining headache. 

PMID- 24433361
TI  - European Medicines Agency initiatives and perspectives on pharmacogenomics.
AB  - Pharmacogenomics, the study of variations of DNA and RNA characteristics as
      related to drug response, has become an integral part of drug development and
      pharmacovigilance, as reflected by the incorporation of pharmacogenomic data in
      EU product information. In this short review article, we describe recent European
      Medicines Agency initiatives intended to support further the implementation of
      pharmacogenomics in drug development and surveillance so that patients and the
      public can benefit from advances in genomic science and technology. 

PMID- 24433362
TI  - Cats with inflammatory bowel disease and intestinal small cell lymphoma have low
      serum concentrations of 25-hydroxyvitamin D.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) and intestinal small cell lymphoma
      (ISCL) are common diseases in cats. The prevalence of alterations in the serum
      concentrations of fat soluble vitamins, such as vitamin D, in cats with IBD and
      ISCL is unknown. HYPOTHESIS/OBJECTIVES: The objective of this study was to
      measure serum 25 hydroxyvitamin D (25[OH]D) concentrations in cats with IBD or
      ISCL. Serum 25(OH)D also was measured in healthy cats, and in hospitalized ill
      cats with nongastrointestinal diseases. ANIMALS: Eighty-four cats were included
      in the study: 23 in the healthy group, 41 in the hospitalized ill group, and 20
      in the IBD/ISCL group. METHODS: Retrospective study. Serum samples for vitamin D
      analysis were frozen at -20 degrees C until serum 25(OH)D was measured by high
      performance liquid chromatography (HPLC). RESULTS: Although there was overlap in
      serum 25(OH)D concentrations among the 3 groups, serum 25(OH)D concentrations
      were significantly lower in the cats with IBD or ISCL compared to healthy cats (P
      < .0001) and hospitalized ill cats (P = .014). In the IBD/ISCL group, there was a
      significant moderate positive correlation between serum albumin and 25(OH)D
      concentrations (r = 0.58, P = .018). CONCLUSION AND CLINICAL IMPORTANCE: The
      median serum concentration of 25(OH)D was significantly lower in cats with
      IBD/ISCL than in healthy cats and in hospitalized ill cats. Additional studies
      are required to elucidate the mechanism of hypovitaminosis D in cats with
      gastrointestinal diseases, to define the best management strategy to treat this
      complication, and to investigate its potential prognostic implications.

PMID- 24433363
TI  - Potential side effect of propofol and sevoflurane for anesthesia of anti-NMDA-R
      encephalitis.
AB  - BACKGROUND: Many anesthetic drugs interact with the NMDA receptor and may
      therefore alter the clinical presentation of anti-NMDA-R encephalitis. CASE
      PRESENTATION: A 24-year-old woman was admitted to hospital for decreased
      consciousness and hyperthermia. Cerebrospinal fluid analysis revealed lymphocytic
      pleocytosis, and elevated protein. Cultures were negative. Patient state worsened
      with agitation, facial dyskinesia, ocular deviation, and limb dystonia. Diagnosis
      of anti-NMDA-R encephalitis was evidenced by specific antibodies. High doses of
      methylprednisolone were administered. CT scan disclosed an ovarian teratoma and
      tumor resection was scheduled under anesthesia with propofol, sufentanil,
      atracurium and sevoflurane. Sedation after surgery was maintained with propofol.
      Rapidly after surgery, patient's condition deteriorated with increase of
      dyskinesias, and two tonic-clonic generalized seizure events. CONCLUSION: In
      patients with anti-NMDA-R encephalitis, anesthesia using benzodiazepines, opiates
      and curares, which fail to interfere with the NMDA pathway, should be preferred.

PMID- 24433364
TI  - Chaos and unpredictability in evolution.
AB  - The possibility of complicated dynamic behavior driven by nonlinear feedbacks in
      dynamical systems has revolutionized science in the latter part of the last
      century. Yet despite examples of complicated frequency dynamics, the possibility
      of long-term evolutionary chaos is rarely considered. The concept of "survival of
      the fittest" is central to much evolutionary thinking and embodies a perspective
      of evolution as a directional optimization process exhibiting simple, predictable
      dynamics. This perspective is adequate for simple scenarios, when frequency
      independent selection acts on scalar phenotypes. However, in most organisms many
      phenotypic properties combine in complicated ways to determine ecological
      interactions, and hence frequency-dependent selection. Therefore, it is natural
      to consider models for evolutionary dynamics generated by frequency-dependent
      selection acting simultaneously on many different phenotypes. Here we show that
      complicated, chaotic dynamics of long-term evolutionary trajectories in phenotype
      space is very common in a large class of such models when the dimension of
      phenotype space is large, and when there are selective interactions between the
      phenotypic components. Our results suggest that the perspective of evolution as a
      process with simple, predictable dynamics covers only a small fragment of long
      term evolution. 

PMID- 24433365
TI  - Patient satisfaction with intravenous acetaminophen: a pooled analysis of five
      randomized, placebo-controlled studies in the acute postoperative setting.
AB  - Intravenous (IV) acetaminophen has been shown to reduce postoperative pain and
      opioid consumption, which may lead to increased patient satisfaction. To
      determine the effect IV acetaminophen has on patient satisfaction, a pooled
      analysis from methodologically homogenous studies was conducted. We obtained
      patient-level data from five randomized, placebo-controlled studies in adults
      undergoing elective surgery in which patient satisfaction was measured using a 4
      point categorical rating scale. The primary endpoint was "excellent" satisfaction
      and the secondary endpoint was "good" or "excellent" satisfaction at 24 hr after
      first study drug administration. Bivariate analyses were conducted using the chi
      square test and Student's t-test and multivariable analyses were conducted using
      logistic regression analysis. Patients receiving IV acetaminophen were more than
      twice as likely as those who received placebo to report "excellent" patient
      satisfaction ratings (32.3% vs. 15.9%, respectively). Of all variables that
      remained statistically significant in the multivariable analysis (i.e., type of
      surgery, duration of anesthesia, last pain rating, and opioid consumption), IV
      acetaminophen had the strongest positive effect on "excellent" patient
      satisfaction with an odds ratio of 2.76 (95% CI 1.81-4.23). Results for
      "excellent" or "good" satisfaction were similar. When given as part of a
      perioperative analgesic regimen, IV acetaminophen was associated with
      significantly improved patient satisfaction. 

PMID- 24433366
TI  - Awareness of impending death for residents of long-term care facilities.
AB  - AIM: To explore awareness of impending death for very old persons in long-term
      care facilities. BACKGROUND: The trajectories of decline that are associated with
      chronic progressive diseases in advanced old age have few prognostic markers.
      Consequently, it is difficult to determine when to start palliative or end-of
      life care. DESIGN: Mixed methods. METHODS: Data were collected in three long-term
      care facilities in Canada. Statistical data were subjected to basic descriptive
      analysis. Qualitative data were collected using methods commonly associated with
      ethnography including interviews, focus groups, observations and artefact review.
      Constant-comparative analysis of qualitative data occurred as data were
      collected. RESULTS: A 2-stage layered awareness of impending death was
      identified: first generalised and then clinical awareness. Generalised awareness
      was characterised by an understanding of human mortality and an understanding of
      the person's nearness to the end of an expected lifespan. Care routines and use
      of resources were not influenced by this early awareness. Clinical awareness of
      impending death was later acknowledged when health status changes suggested that
      death was likely within a few hours or days. The care then changed substantially
      to palliative in nature. CONCLUSIONS: Despite an awareness that death occurs
      naturally at the end of a long life and/or long illness, a serious decline
      towards death was not noticed or acknowledged until the last few hours or days of
      life, thus limiting palliative care to late-stage pain and symptom management.
      IMPLICATIONS FOR PRACTICE: Although this late-stage awareness of impending death
      is arguably the first necessary step for a change in nursing homes to a
      palliative-oriented approach to care for people who are nearing death in late
      life, timely acknowledgement of the potential for death is needed to facilitate
      improvements in care for residents of long-term facilities.

PMID- 24433367
TI  - The new era of multiple sclerosis therapy.

PMID- 24433369
TI  - Measuring pain intensity in patients with neck pain: does it matter how you do
      it?
AB  - The aim of this study was to investigate whether variations in the way that pain
      intensity is measured in patients with neck pain influences the magnitude of pain
      ratings. The study uses data from 3 longitudinal studies (n = 361 at baseline) on
      people with neck pain due to whiplash injuries. Pain measures included verbal
      rating scales, numerical rating scales and a visual analog scale. Different
      measures asked patient to rate current pain, average pain over 24 hours, over 1
      week, or over 4 weeks. Scores were converted to a 0-100 scale and tracked over
      time, correlations between measures were calculated. Mixed models regression was
      used to explore the factors which influenced the differences between scores on
      the measures. Scores on the different measures were significantly different from
      each other in each dataset (P < 0.02). The effect of recall period was
      significant in all datasets and the effect of number of response options was
      significant in 2 of 3 datasets. Pain intensity ratings appear to be sensitive to
      method of measurement. It is likely the length of recall time (eg, pain today vs.
      average pain over 4 weeks) has a significant influence on pain ratings. The
      influence of number of response options is less certain. Systematic reviewers
      should not uncritically rescale and pool absolute pain scores from instruments
      with varying scale descriptors or recall periods.

PMID- 24433370
TI  - Relationship between ankle brachial index and ejection fraction in elderly
      Egyptians with ischemic heart disease.
AB  - AIM: There is a high prevalence of combined peripheral and coronary artery
      disease, with increasing morbidity and decline in cardiac function. The aim of
      the present study was to find an association between ankle brachial index, a non
      invasive measure of peripheral artery disease, and ejection fraction in elderly
      patients with severe coronary artery disease. METHODS: A case-control study
      recruiting 200 elderly male and female ischemic patients in Ain Shams University
      hospitals was carried out. All participants had significant coronary artery
      disease lesions in coronary angiography carried out before the study. Cases and
      controls were divided according to ankle brachial index, with further subdivision
      of each group according to age. Measurements include: ankle brachial index using
      Bistos handheld vascular Doppler (BT 200V,8 MHz), electrocardiography and
      echocardiography showing left ventricular ejection fraction. Coronary artery
      disease severity was estimated using the number of diseased vessels. RESULTS: The
      mean age of our study group was 67 years. Although our participants had mild to
      moderate peripheral artery disease, ejection fraction statistically decreased
      with decreasing ankle brachial index, being the lowest in participants aged > 70
      years (46.84 +/- 9.82 years) and the highest in controls aged >70 years (53.02 +/
      5.53 years; P = 0.009). Ejection fraction was positively correlated with ankle
      brachial index (P = 0.011, 0.006) for cases and controls, respectively.
      CONCLUSION: Ankle brachial index can correlate with ejection fraction in elderly
      ischemic Egyptians with more severe coronary artery disease.

PMID- 24433371
TI  - Influenza vaccination, inverse care and homelessness: cross-sectional survey of
      eligibility and uptake during the 2011/12 season in London.
AB  - BACKGROUND: Influenza vaccination eligibility and uptake among homeless adults
      has not been previously assessed in the UK. This cross-sectional survey aimed to
      measure the proportion of homeless people visited by an NHS outreach service
      (Find and Treat) who were eligible for and had received vaccination during
      2011/12. METHODS: A cross-sectional survey was carried out in 27 separate
      homeless hostels, day centres and drug services in London between July and August
      in 2012. Eligibility for the survey was by virtue of being in attendance at one
      of 27 venues visited by Find and Treat. No specific exclusion criteria were used.
      RESULTS: 455 clients took part in the survey out of 592 approached (76.9%). A
      total of 190 homeless people (41.8%; 95% CI: 34.5,50.5) were eligible for
      influenza vaccination. In those aged 16-64, eligibility due to clinical risk
      factors was 38.9% (95% CI: 31.5,48.2). Uptake of vaccination in homeless 16-64
      year olds with a clinical risk factor during the 2011/12 influenza season was
      23.7% (95% CI: 19.8,28.3) compared to national levels of 53.2% (excluding
      pregnant women). In those aged over 65, uptake was 42.9% (95% CI: 16.7,100.0)
      compared with 74.0% nationally. CONCLUSIONS: This study demonstrates that the
      homeless population have high levels of chronic health problems predisposing them
      to severe complications of influenza, but vaccine uptake levels that are less
      than half those seen among eligible GP patient groups in England. It provides a
      clear example of the health inequalities and inverse care law that impact this
      population. The results of this study provide strong justification for
      intensifying efforts to ensure homeless people have access to influenza
      vaccination.

PMID- 24433372
TI  - Lasers and laser-like devices: part two.
AB  - Part two of this review series evaluates the use of lasers and laser-like devices
      in dermatology based on published evidence and the collective experience of the
      senior authors. Dermatologists can laser-treat a wide range of dermatoses,
      including vascular, pigmentary, textural, benign proliferative and premalignant
      conditions. Some of these conditions include vascular malformation, haemangioma,
      facial telangiectases, cafe-au-lait macules, naevi of Ota, lentigines, acne
      scarring, rhytides, rhinophyma and miscellaneous skin lesions. Photodynamic
      therapy with lasers and intense pulsed light is addressed, with particular
      reference to actinic keratosis and actinic cheilitis. A treatment algorithm for
      acne scarring based on scar morphology and severity is comprehensively outlined.
      Following from part one, the various devices are matched to the corresponding
      dermatological conditions with representative pictorial case vignettes
      illustrating likely clinical outcomes as well as limitations and potential
      complications of the various laser and light therapies. 

PMID- 24433373
TI  - Suspected allergic contact dermatitis to iodopropynyl butylcarbamate in an
      alcohol hand rub commonly used in Australian health-care settings.
AB  - We report a case of suspected allergic contact dermatitis to the preservative and
      uncommon allergen iodopropynyl butylcarbamate, found in Microshield Angel hand
      gel, a skin cleanser commonly used in Australian health-care settings. 

PMID- 24433375
TI  - Chemical leucoderma induced by homemade lemon toner.

PMID- 24433376
TI  - Dermatitis artefacta presenting as a recurrent skin eruption in a patient with
      1p36 deletion syndrome.

PMID- 24433377
TI  - Mutation analysis of the ADAR1 gene in a Chinese Family with dyschromatosis
      symmetrica hereditaria.

PMID- 24433378
TI  - The range and prevalence of clinical signs and conformation associated with
      lameness in working draught donkeys in Pakistan.
AB  - REASONS FOR PERFORMING THE STUDY: Lameness is prevalent in working donkeys and
      has major welfare implications; however, a detailed study of the associated
      clinical signs is lacking. OBJECTIVES: To describe the range and prevalence of
      clinical signs and conformation associated with lameness in working draught
      donkeys. STUDY DESIGN: Prospective, cross-sectional, observational study.
      METHODS: Data were collected from 102 working draught donkeys in Pakistan. A
      lameness assessment adapted for working donkeys was used to record clinical signs
      of lameness, gait, limb conformation and pain responses in the feet, limbs and
      spine using observation, palpation and manipulation. Lameness at the walk was
      scored from 0 to 10 (sound to nonweightbearing). RESULTS: Every donkey examined
      had gait abnormalities, with 5% having a nonweightbearing limb. Lameness was
      significantly more severe with older age, lower body condition score and forward
      at-the-knee conformation. More severe lameness was also associated with pain
      responses in the hoof walls, palpation of limb joints and spinal flexion. Joint,
      tendon and foot pathology was highly prevalent, as well as pain responses to
      joint flexion and spinal manipulation. Conformational abnormalities showed
      lateral asymmetries. CONCLUSIONS: Over 98% of the world's 42.2 million donkeys
      are in low-income countries, most being used for work. The high prevalence of
      lameness, pain and multiple limb and spinal abnormalities in working donkeys is
      of great welfare concern and highlights the complexity of addressing this
      problem. This standardised lameness assessment can be used when implementing and
      monitoring interventions to reduce lameness prevalence in working donkeys.

PMID- 24433379
TI  - A review of the nutritional value of legumes and their effects on obesity and its
      related co-morbidities.
AB  - Since the 1970s, the proportion of overweight and obese people in the United
      States has grown at an alarming rate. An awareness of the consequences of obesity
      on the health and well-being of individuals is evident in the plethora of
      strategic plans at the local and national levels, most of which have largely
      fallen short of their goals. If interventions continue to be unsuccessful, it is
      estimated that approximately three of four Americans will be overweight or obese
      by 2020. Prevention of excess weight gain can be accomplished with relatively
      small changes in lifestyle behaviours to control body weight. Small sustainable
      changes are perhaps better than efforts to achieve larger changes that cannot be
      sustained. Legumes can be a valuable food by which the needs of the
      undernourished or under-served populations could be met. They can be incorporated
      into meat products, such as sausages and burgers, to lower the energy density of
      these foods while providing important nutrients. Replacing energy-dense foods
      with legumes has been shown to have beneficial effects on the prevention and
      management of obesity and related disorders, such as cardiovascular disease,
      diabetes and the metabolic syndrome. This review explores the nutritional value
      and obesity-related health benefits of legume consumption while focusing on
      pulses. 

PMID- 24433380
TI  - The effect of consignment to broodmare sales on physiological stress measured by
      faecal glucocorticoid metabolites in pregnant Thoroughbred mares.
AB  - BACKGROUND: Validation of a method for the minimally-invasive measurement of
      physiological stress will help understanding of risk factors that may contribute
      to stress-associated events including recrudescence of Equid herpesvirus (EHV),
      which is anecdotally associated with sales consignment of pregnant Thoroughbred
      mares. In this study we compared two similar groups of late-gestation
      Thoroughbred broodmares on the same farm: a consigned Sales group (N = 8) and a
      non-consigned Control group (N = 6). The Sales mares were separated from their
      paddock companions and grouped prior to their preparation for, transport to, and
      return from the sales venue. Both groups were monitored by sampling at regular
      intervals from 5 days prior to until 14 days after the sales date (D0) to measure
      physiological stress in terms of changes in faecal glucocorticoid metabolite
      (FGM) concentrations, and for event-related viral recrudescence via daily body
      temperature measurements and periodic nasal swabs for PCR analysis for EHV-1 and 
      4 DNA. RESULTS: In both groups, FGM levels increased post-sales before returning
      to pre-sales levels. Specifically, FGM concentrations in the Sales mares were
      significantly higher on D + 3 and D + 10 than on D-4 and D-3 (F = 12.03, P <
      0.0001, Post hoc: P = 0.0003-0.0008) and in the Control group FGM concentrations
      were higher on D + 10 than D-4 (F = 5.52, P = 0.004, Post hoc: P = 0.005).
      Interestingly, mean FGM levels in Control mares were significantly higher at 4 of
      the 5 sampling points (t = 5.64-2.25, p = 0.0001-0.044). Only one (Sales) mare
      showed PCR evidence of EHV-1 shedding. CONCLUSIONS: Using FGM to measure
      physiological stress was supported by the increases observed in all mares after
      Sales consignment, including those not consigned to the sale. Monitoring FGM
      levels therefore represents an appropriate, minimally-invasive method for future
      studies to assess the contribution of physiological stress to EHV recrudescence
      in horses transported to sales or equestrian events.

PMID- 24433381
TI  - Anatomical comparison of sciatic nerves between adults and newborns: clinical
      implications for ultrasound guided block.
AB  - The sciatic nerve (SN) is easily blocked under ultrasound guidance by identifying
      either the SN common trunk or its two components: the tibial nerve (TN) and the
      common peroneal nerve (CPN). The authors investigate whether there are anatomical
      differences between newborns and adults. The SN, TN and CPN of both lower
      extremities in 24 (11 neonatal and 13 adults) formolized cadavers were dissected.
      Distances were measured from the origin of the SN (passing under the piriformis
      muscle) to its division into TN and CPN, and from there to the popliteal crease.
      The sciatic/thigh coefficient (proportion relating SN length to thigh length) and
      the variation coefficient for the SN were calculated. The distance from the
      popliteal crease to the SN division was significantly shorter in neonates than in
      adults (1.04 +/- 0.9 cm vs. 5.6 +/- 5.1 cm, P = 0.0003). In addition, the
      neonatal SN divided at a proportionally more distal position in the thigh than it
      did in adults (86 +/- 13 vs. 74 +/- 15%, P = 0.0059). However, the coefficient of
      variation between the SN-division distances was not statistically different in
      infants and adults (12.8 vs. 18.2%, P = 0.4345). The variations in the point of
      SN division seen in the adult SN are already seen in the neonatal period, but in
      newborns the SN divided in a more distal position in relation to the thigh than
      in adults, so this finding of anatomical variability in neonates suggests that
      ultrasound guidance can be useful when performing a SN block in these small
      patients. 

PMID- 24433382
TI  - Fibre type composition in the lumbar perivertebral muscles of primates:
      implications for the evolution of orthogrady in hominoids.
AB  - The axial musculoskeletal system is important for the static and dynamic control
      of the body during both locomotor and non-locomotor behaviour. As a consequence,
      major evolutionary changes in the positional habits of a species are reflected by
      morpho-functional adaptations of the axial system. Because of the remarkable
      phenotypic plasticity of muscle tissue, a close relationship exists between
      muscle morphology and function. One way to explore major evolutionary transitions
      in muscle function is therefore by comparative analysis of fibre type
      composition. In this study, the three-dimensional distribution of slow and fast
      muscle fibres was analysed in the lumbar perivertebral muscles of two lemuriform
      (mouse lemur, brown lemur) and four hominoid primate species (white-handed
      gibbon, orangutan, bonobo, chimpanzee) in order to develop a plausible scenario
      for the evolution of the contractile properties of the axial muscles in hominoids
      and to discern possible changes in muscle physiology that were associated with
      the evolution of orthogrady. Similar to all previously studied quadrupedal
      mammals, the lemuriform primates in this study exhibited a morpho-functional
      dichotomy between deep slow contracting local stabilizer muscles and superficial
      fast contracting global mobilizers and stabilizers and thus retained the fibre
      distribution pattern typical for quadrupedal non-primates. In contrast, the
      hominoid primates showed no regionalization of the fibre types, similar to
      previous observations in Homo. We suggest that this homogeneous fibre composition
      is associated with the high functional versatility of the axial musculature that
      was brought about by the evolution of orthograde behaviours and reflects the
      broad range of mechanical demands acting on the trunk in orthograde hominoids.
      Because orthogrady is a derived character of euhominoids, the uniform fibre type
      distribution is hypothesized to coincide with the evolution of orthograde
      behaviours. 

PMID- 24433383
TI  - Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla).
AB  - European eels live most of their lives in freshwater until spawning migration to
      the Sargasso Sea. During seawater adaptation, eels modify their physiology, and
      their digestive system adapts to the new environment, drinking salt water to
      compensate for the continuous water loss. In that period, eels stop feeding until
      spawning. Thus, the eel represents a unique model to understand the adaptive
      changes of the enteric nervous system (ENS) to modified salinity and starvation.
      To this purpose, we assessed and compared the enteric neuronal density in the
      cranial portion of the intestine of freshwater eels (control), lagoon eels
      captured in brackish water before their migration to the Sargasso Sea (T0), and
      starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of
      starvation and treatment with standardized carp pituitary extract). Furthermore,
      we analyzed the modification of intestinal neuronal density of hormonally
      untreated eels during prolonged starvation (10 weeks) in seawater and freshwater.
      The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive
      (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The
      number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater
      to the salty water habitat (control > T0 > T18; P < 0.05). Compared with
      freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly
      increased (P < 0.05) in the intestine of starved untreated salt water eels. In
      conclusion, high salinity evokes enteric neuroplasticity as indicated by the
      increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing
      to maintaining the body homeostasis of this fish in extreme conditions. 

PMID- 24433384
TI  - Abstracts of the Anatomical Society Summer Meeting 2013, July 4-5, 2013, Dublin,
      Ireland.

PMID- 24433385
TI  - Ability of the Tightrope(r) and percutaneous lateral fabellar suture techniques
      to control cranial tibial translation.
AB  - OBJECTIVE: To compare the ability of the Tightrope(r) (TR) cranial cruciate
      ligament (CCL) technique, percutaneous lateral fabella suture (pLFS) technique,
      and normal CCL to control cranial tibial translation (CTT). STUDY DESIGN: In
      vitro biomechanical study. SAMPLE POPULATION: Cadaveric canine pelvic limbs (n =
      18 pairs). METHODS: Six small animal surgical residents (1 pair each) and a
      Diplomate of the American College of Veterinary Surgeons (10 pairs) performed TR
      and pLFS techniques on paired limbs. Two intact limb pairs served as controls.
      Limbs were assessed by palpation, radiographs, and dissection before mechanical
      testing of resistance to CTT. Forces resisted during displacement were compared
      between groups with a mixed ANOVA and post hoc tests. RESULTS: With 5 mm of
      displacement, the pLFS resisted 72 +/- 45 N and the TR resisted 66 +/- 48 N of
      load. The intact CCL resisted 400 +/- 35 N. The intact CCL resisted displacement
      significantly more than either surgical technique. CONCLUSIONS: TR and pLFS had
      similar ability to resist CTT but neither restored the biomechanical properties
      of an intact CCL.

PMID- 24433386
TI  - Clinical findings, diagnostic test results, and treatment outcome in cats with
      spontaneous hyperadrenocorticism: 30 cases.
AB  - BACKGROUND: Spontaneous hyperadrenocorticism (HAC) is rare in cats. Clinical
      findings, diagnostic test results, and response to various treatment options must
      be better characterized. OBJECTIVES: To report the clinical presentation,
      clinicopathologic findings, diagnostic imaging results, and response to treatment
      of cats with HAC. ANIMALS: Cats with spontaneous HAC. METHODS: Retrospective
      descriptive case series. RESULTS: Thirty cats (15 neutered males, 15 spayed
      females; age, 4.0-17.6 years [median, 13.0 years]) were identified from 10
      veterinary referral institutions. The most common reason for referral was
      unregulated diabetes mellitus; dermatologic abnormalities were the most frequent
      physical examination finding. Low-dose dexamethasone suppression test results
      were consistent with HAC in 27 of 28 cats (96%), whereas ACTH stimulation testing
      was suggestive of HAC in only 9 of 16 cats (56%). Ultrasonographic appearance of
      the adrenal glands was consistent with the final clinical diagnosis of PDH or ADH
      in 28 of 30 cats (93%). Of the 17 cats available for follow-up at least 1 month
      beyond initial diagnosis of HAC, improved quality of life was reported most
      commonly in cats with PDH treated with trilostane. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Dermatologic abnormalities or unregulated diabetes mellitus are the
      most likely reasons for initial referral of cats with HAC. The dexamethasone
      suppression test is recommended over ACTH stimulation for initial screening of
      cats with suspected HAC. Diagnostic imaging of the adrenal glands may allow rapid
      and accurate differentiation of PDH from ADH in cats with confirmed disease, but
      additional prospective studies are needed.

PMID- 24433388
TI  - Pulse in pulse intense pulsed light for melasma treatment: a pilot study.
AB  - BACKGROUND: A new type of intense pulsed light IPL with pulse-in-pulse (PIP) mode
      (multiple fractionated subpulses in one pulse width) has recently been developed.
      OBJECTIVE: To evaluate the clinical efficacy and safety of PIP IPL in patients
      with melasma. MATERIALS AND METHODS: Half of each patient's face was treated with
      IPL and six treatment sessions with a low-fluence quality-switched neodymium
      doped yttrium aluminum garnet laser (IPL/T) every 2 weeks. The other half was
      treated with PIP IPL. Outcome assessments included photography, modified Melasma
      Area and Severity Index (MASI) score, and patient satisfaction. The melanin and
      erythema indices were used for objective evaluation. Patients were followed up
      for 6 months after the last treatment. RESULTS: All patients completed the study
      successfully. On both treated sides, the melanin index decreased significantly
      after treatment. The modified MASI score also fell 54.4% on the PIP IPL side and
      50.0% on the IPL/T side. No patients reported serious aggravation of melasma for
      6 months after the last treatment. Patients favored PIP IPL due to less
      discomfort during and after treatments. CONCLUSION: PIP IPL may be a safe and
      promising treatment for melasma.

PMID- 24433387
TI  - The pro-inflammatory potential of T cells in juvenile-onset systemic lupus
      erythematosus.
AB  - BACKGROUND: T cells are important to systemic lupus erythematosus (SLE) disease
      progression. This study determined the pro-inflammatory potential of T cells
      within the rare condition juvenile-onset SLE (JSLE). METHOD: IL-17A and Th1/Th2
      related cytokine concentrations were measured in plasma/serum from JSLE patients
      (n = 19, n = 11) and HC (n = 18, n = 7). IL17A, RORC, IL23 and IL23R mRNA were
      measured in peripheral blood mononuclear cells (PBMCs) from JSLE and healthy
      controls (HC) (n = 12). Th17-associated cytokine expression was analysed in the
      supernatant of CD3/CD28 activated JSLE (n = 7) and HC (n = 6) PBMCs. RESULTS:
      JSLE plasma IL-17A level (21.5 +/- 5.2 pg/ml) was higher compared to HC (7.2 +/-
      2.5 pg/ml, p = 0.028). No differences were found in Th1/Th2 cytokines levels. IL
      = 17A (p = 0.022), IL-6 (p = 0.028) and IL-21 (p = 0.003) concentrations were
      increased in supernatants from activated JSLE PBMCs. IL-17 F (p = 0.50) and IL-22
      (p = 0.43) were also increased but were not statistically significant. IL17A and
      IL23 mRNA was significantly higher in JSLE PBMCs (p = 0.018 and p = 0.01).
      CONCLUSION: JSLE T cells have an increased ability to secrete Th17 associated
      cytokines once activated, which could contribute to the pro-inflammatory disease
      phenotype seen in these patients.

PMID- 24433389
TI  - Niche and range size patterns suggest that speciation begins in small,
      ecologically diverged populations in North American monkeyflowers (Mimulus spp.).
AB  - Closely related species (e.g., sister taxa) often occupy very different
      ecological niches and can exhibit large differences in geographic distributions
      despite their shared evolutionary history. Budding speciation is one process that
      may partially explain how differences in niche and distribution characteristics
      may rapidly evolve. Budding speciation is the process through which new species
      form as initially small colonizing populations that acquire reproductive
      isolation. This mode of species formation predicts that, at the time of
      speciation, sister species should have highly asymmetrical distributions. We
      tested this hypothesis in North American monkeyflowers, a diverse clade with a
      robust phylogeny, using data on geographical ranges, climate, and plant community
      attributes. We found that recently diverged sister pairs have highly asymmetrical
      ranges and niche breadths, relative to older sister pairs. Additionally, we found
      that sister species occupy distinct environmental niche positions, and that 80%
      of sister species have completely or partially overlapping distributions (i.e.,
      are broadly sympatric). Together, these results suggest that budding speciation
      has occurred frequently in Mimulus, that it has likely taken place both inside
      the range and on the range periphery, and that observed divergences in habitat
      and resource use could be associated with speciation in small populations. 

PMID- 24433390
TI  - Food items contributing most to variation in antioxidant intake; a cross
      sectional study among Norwegian women.
AB  - BACKGROUND: Fruit and vegetable intake has been found to reduce the risk of
      cardiovascular disease, certain types of cancer and diabetes mellitus. It is
      possible that antioxidants play a large part in this protective effect. However,
      which foods account for the variation in antioxidant intake in a population is
      not very clear. We used food frequency data from a population-based sample of
      women to identify the food items that contributed most to the variation in
      antioxidant intake in Norwegian diet. METHODS: We used data from a study
      conducted among participants in the Norwegian Breast Cancer Screening Program
      (NBCSP), the national program which invites women aged 50-69 years to
      mammographic screening every 2 years. A subset of 6514 women who attended the
      screening in 2006/2007 completed a food frequency questionnaire (FFQ). Daily
      intake of energy, nutrients and antioxidant intake were estimated. We used
      multiple linear regression analysis to capture the variation in antioxidant
      intake. RESULTS: The mean (SD) antioxidant intake was 23.0 (8.5) mmol/day. Coffee
      consumption explained 54% of the variation in antioxidant intake, while fruits
      and vegetables explained 22%. The twenty food items that contributed most to the
      total variation in antioxidant intake explained 98% of the variation in intake.
      These included different types of coffee, tea, red wine, blueberries, walnuts,
      oranges, cinnamon and broccoli. CONCLUSIONS: In this study we identified a list
      of food items which capture the variation in antioxidant intake among these
      women. The major contributors to dietary total antioxidant intake were coffee,
      tea, red wine, blueberries, walnuts, oranges, cinnamon and broccoli. These items
      should be assessed in as much detail as possible in studies that wish to capture
      the variation in antioxidant intake.

PMID- 24433392
TI  - Exogenous 5,6-dimethylbenzimidazole caused production of a non-functional
      tetrachloroethene reductive dehalogenase in Sulfurospirillum multivorans.
AB  - Corrinoid-dependent reductive dehalogenation is mediated by phylogenetically
      diverse anaerobic bacteria that either synthesize corrinoids de novo or are
      dependent on corrinoid salvaging from the environment. The tetrachloroethene
      (PCE) reductive dehalogenase (PceA) of the Gram-negative Epsilonproteobacterium
      Sulfurospirillum multivorans harbours a norpseudo-B12 as corrinoid cofactor.
      Norpseudo-B12 differs from coenzyme B12 in the nucleotide loop structure. Adenine
      instead of 5,6-dimethylbenzimidazole (DMB) serves as lower ligand base of the
      central cobalt ion, and the nucleotide loop of norpseudo-B12 lacks a methyl group
      at position 176. In this study, S. multivorans was grown anaerobically with PCE
      in the presence of DMB. At a DMB concentration of 25 MUM, the adenine moiety in
      the nucleotide loop of norpseudo-B12 was quantitatively replaced by DMB. The
      formation of the DMB-containing nor-B12 severely affected PCE-dependent growth
      and the PceA activity. In DMB-treated cells processing of the cytoplasmic PceA
      precursor was impeded, a result pointing to retarded cofactor incorporation. PceA
      enriched from cells cultivated with DMB contained nor-B12 . Nor-B12 purified from
      cells grown in the presence of DMB mediated the abiotic reductive dehalogenation
      of trichloroacetate to dichloroacetate at a 25-fold lower rate in comparison with
      norpseudo-B12 , a fact underpinning the relevance of norpseudo-B12 as efficient
      catalyst for reductive dehalogenation in general. 

PMID- 24433394
TI  - Non-invasive prenatal testing for trisomy 21: a cross-sectional survey of service
      users' views and likely uptake.
AB  - OBJECTIVE: To assess the views and likely uptake of non-invasive prenatal testing
      (NIPT) for trisomy 21 among potential service users in the UK. DESIGN: Cross
      sectional survey. SETTING: Four antenatal clinics in England and two websites.
      SAMPLE: A total of 1131 women and partners. METHODS: Questionnaire conducted with
      women (and partners) recruited through antenatal clinics, a random sample of
      members of the website Mumsnet, and viewers of the website and Facebook page of
      the support group Antenatal Results and Choices (ARC). MAIN OUTCOME MEASURES:
      Factors impacting decision-making towards prenatal testing; views on NIPT,
      including service delivery and likely uptake; hypothetical scenarios, focused on
      current screening, invasive testing, and NIPT offered to women with a high-risk
      screening result. RESULTS: The vast majority (95.7%; 1071/1119; 95% CI 94.4
      96.8%) thought NIPT was a positive development in prenatal care, with 88.2%
      (972/1103; 95% CI 86.1-90%) indicating that they would use the test, including
      respondents who would currently decline trisomy 21 screening (P < 0.001). Of the
      respondents who would have NIPT, 30.7% (299/973; 95% CI = 27.8-33.7%) said that
      they were 'likely' to terminate an affected pregnancy (including those who would
      currently decline screening or invasive testing), and 36.5% (355/973; 95% CI 33.5
      39.6%) were 'not likely' to terminate an affected pregnancy. Respondents
      overwhelmingly indicated that safety for the baby was the most important
      attribute of NIPT (70.1%; 712/1015; 95% CI 67.2-73%). CONCLUSION: Respondents
      were overwhelmingly positive towards the introduction of NIPT. Uptake is likely
      to be high, and includes women who currently decline screening as well as those
      who will use the test for information only. Pre-test counselling to ensure that
      women understand the implications of the test result is essential.

PMID- 24433393
TI  - Improving antibiotic prescribing for children in the resource-poor setting.
AB  - Antibiotics are a critically important part of paediatric medical care in low-
      and middle-income countries (LMICs), where infectious diseases are the leading
      cause of child mortality. The World Health Organization estimates that >50% of
      all medicines are prescribed, dispensed or sold inappropriately and that half of
      all patients do not take their medicines correctly. Given the rising prevalence
      of antimicrobial resistance globally, inappropriate antibiotic use is of
      international concern, and countries struggle to implement basic policies
      promoting rational antibiotic use. Many barriers to rational paediatric
      prescribing in LMICs persist. The World Health Organization initiatives, such as
      'Make medicines child size', the Model List of Essential Medicines for Children
      and the Model Formulary for Children, have been significant steps forward.
      Continued strategies to improve access to appropriate drugs and formulations, in
      conjunction with improved evidence-based clinical guidelines and dosing
      recommendations, are essential to the success of such initiatives on both a
      national and an international level. This paper provides an overview of these
      issues and considers future developments that may improve LMIC antibiotic
      prescribing. 

PMID- 24433395
TI  - Associations between life contexts and early sexual initiation among young women
      in France.
AB  - CONTEXT: Early sexual initiation (before age 16) has been linked to an increased
      risk of teenage pregnancy and STDs. Most research on correlates of early sexual
      initiation is from the United States; no similar work has been conducted in
      France, where the sociocultural environment differs. METHODS: Cross-sectional
      data from the 2010 Health Behaviour in School-Aged Children survey were used to
      examine the relationships of personal, family, peer, school and neighborhood
      characteristics with early sexual initiation among 1,094 French females in grades
      8-10. Two-level logistic regressions were used to identify associations. RESULTS:
      Twenty-five percent of respondents had had sex before age 16. Early sexual
      initiation was primarily -associated with individual-level characteristics. Young
      women had an elevated likelihood of having initiated sex early if they went out
      after school at least four times a week (odds ratio, 2.0), had repeated a grade
      (1.8), lived with a single parent or in a stepfamily (1.8 and 1.5, respectively),
      perceived a low level of parental monitoring (1.6) or had two or more male
      friends (2.8). At the environmental level, respondents who attended school in
      areas with a high proportion of residents who were foreigners had a reduced
      likelihood of having initiated sex early (0.5-0.6). CONCLUSIONS: Although early
      sexual initiation in France was essentially linked to individual-level variables,
      further research is needed to understand its relationship with neighborhood
      characteristics. Such studies should include additional environmental variables,
      test new hypotheses and employ a longitudinal approach.

PMID- 24433396
TI  - Investigations on the antiretroviral activity of carbon nanotubes using
      computational molecular approach.
AB  - Carbon nanotubes are the interesting class of materials with wide range of
      applications. They have excellent physical, chemical and electrical properties.
      Numerous reports were made on the antiviral activities of carbon nanotubes.
      However the mechanism of antiviral action is still in infancy. Herein we report,
      our recent novel findings on the molecular interactions of carbon nanotubes with
      the three key target proteins of HIV using computational chemistry approach.
      Armchair, chiral and zigzag CNTs were modeled and used as ligands for the
      interaction studies. The structure of the key proteins involved in HIV mediated
      infection namely HIV- Vpr, Nef and Gag proteins were collected from the PDB
      database. The docking studies were performed to quantify the interaction of the
      CNT with the three different disease targets. Results showed that the carbon
      nanotubes had high binding affinity to these proteins which confirms the
      antagonistic molecular interaction of carbon nanotubes to the disease targets.
      The modeled armchair carbon nanotubes had the binding affinities of -12.4
      Kcal/mole, -20 Kcal/mole and -11.7 Kcal/mole with the Vpr, Nef and Gag proteins
      of HIV. Chiral CNTs also had the maximum affinity of -16.4 Kcal/mole to Nef. The
      binding affinity of chiral CNTs to Vpr and Gag was found to be -10.9 Kcal/mole
      and -10.3 Kcal/mole respectively. The zigzag CNTs had the binding affinity of 
      11.1 Kcal/mole with Vpr, -18.3 Kcal/mole with Nef and -10.9 with Gag
      respectively. The strong molecular interactions suggest the efficacy of CNTs for
      targeting the HIV mediated retroviral infections. 

PMID- 24433397
TI  - Approaches to the treatment of some of the troublesome manifestations of
      sarcoidosis.
AB  - Sarcoidosis can be a major therapeutic challenge given its multiplicity of
      clinical presentations, variable combination of organ involvement and severity,
      and unpredictable longitudinal behaviour. Six manifestations of sarcoidosis are
      especially difficult to manage because of (i) an incomplete knowledge of
      causation - fatigue and small fibre neuropathy, (ii) the rare occurrence in
      sarcoidosis - intra-abdominal complications or (iii) the potentially life
      threatening consequences in some patients - neurological disease, pulmonary
      hypertension and hypercalcaemia. In none of these situations have a prospective,
      double-blind, placebo-controlled trial of any therapy been conducted. Despite
      this absence of any firm evidence base to support therapeutic recommendations,
      these six entities can be extremely problematic for the practising clinician. It
      is for this reason that we have focused in this review on these six disease
      manifestations and provided a synopsis of each problem together with suggested
      treatment approaches, based on an analysis of the current literature.

PMID- 24433398
TI  - Occurrence and molecular characterization of Cryptosporidium in dogs in Henan
      Province, China.
AB  - BACKGROUND: Cryptosporidiosis in dogs has been reported worldwide, involving both
      asymptomatic and diarrheic dogs. Large-scale surveys of Cryptosporidium infection
      in dogs have been performed in some countries using different diagnostic methods.
      But, few data are available on the infection rate and molecular characteristics
      of Cryptosporidium spp. in dogs in China. RESULT: In this study, 770 fecal
      samples from 66 locations in Henan Province were examined. The average
      Cryptosporidium infection rate was 3.8%, with dogs in kennels having the highest
      rate of 7.0% (chi2 = 14.82, P < 0.01). The infection rate was 8.0% in dogs
      younger than 90 days, which was significantly higher than that in the other age
      groups (1.1-3.8%;chi2 = 18.82, P < 0.01). No association was noted between the
      infection rate and the sex of the dogs. Twenty-nine Cryptosporidium-positive
      samples were amplified at the small subunit rRNA (SSU rRNA), 70-kDa heat shock
      protein (HSP70), and actin loci using PCR. Sequence analysis of these amplicons
      identified only Cryptosporidium canis, which showed 100% identity with the
      published sequences of the SSU rRNA, HSP70, and actin genes. CONCLUSIONS: Our
      results confirm that C. canis is popular in the dog population in China,
      considering the large number of dogs in China and the close contact between dogs
      and humans, the role of C. canis in the transmission of human cryptosporidiosis
      warrants attention.

PMID- 24433399
TI  - Procedural results with the self-expanding 31 mm CoreValve aortic bioprosthesis
      in patients with large annuli.
AB  - BACKGROUND: Transcatheter aortic valve implantation has become an established
      treatment for severe aortic stenosis in patients with high surgical risk. Due to
      its specific design, the self-expanding 31 mm CoreValve prosthesis can be
      technically challenging. This is especially true for patients with large annuli
      above 27.5 mm for which the CoreValve 31 mm device is the only option.
      OBJECTIVES: To evaluate procedural results and short-term outcome with the 31 mm
      CoreValve device in patients with large annuli. METHODS: We retrospectively
      analyzed 54 patients in whom we implanted a 31 mm self-expanding CoreValve
      bioprosthesis and compared them to 50 consecutive patients implanted with the
      smaller 29 mm device within the same period of time. RESULTS: Patients with the
      31 mm prosthesis had significantly higher rates of postinterventional pacemaker
      implantations (35% vs. 20%; P = 0.036) despite similar implantation depths (6.5
      +/- 4 vs. 7.5 +/- 4; P = 0.34). However, the number of deep implantations (>8 mm)
      was significantly higher (P = 0.045). No significant difference could be observed
      with respect to cases with >=Grade 2 postinterventional aortic regurgitation (8%
      vs. 12.9%; P = 0.5294). Major vascular complications (4% vs. 3.7%; P = ns), 30
      day mortality (8% vs. 7.7%; P = ns), and major stroke (3.8% vs. 2%; P = ns) were
      not different between the 2 groups. CONCLUSION: Despite the technical challenges,
      procedural results with the 31 mm self-expanding CoreValve prosthesis in large
      anatomies were similar to those with the smaller sized 29 mm version of the
      device. However, postinterventional pacemaker rates were significantly higher in
      the 31 mm cohort despite comparable implantation depths, which might be the
      result of the specific design of the device.

PMID- 24433400
TI  - Technical difficulties during the training phase for Tightrope(r) and
      percutaneous lateral fabellar suture techniques for cranial cruciate ligament
      repair.
AB  - OBJECTIVE: To compare level of difficulty, deviations from technical description
      and postoperative assessment during the training of veterinary students, small
      animal surgical residents, and a board certified surgeon for Tightrope(r) (TR)
      and percutaneous lateral fabella suture (pLFS) techniques for cranial cruciate
      ligament (CCL) repair. STUDY DESIGN: Prospective study. SAMPLE POPULATION:
      Cadaveric canine pelvic limbs (n = 32). METHODS: Sixteen 3rd year veterinary
      students, 6 small animal surgical residents and a Diplomate of the American
      College of Veterinary Surgeons performed the TR and pLFS techniques on paired
      limbs. Perceived level of difficulty, duration of surgery, and technical
      deviations were assessed by questionnaire, radiographs, and dissection. Results
      were compared between techniques with McNemar's test. RESULTS: The TR procedure
      was perceived as more technically demanding than the pLFS by veterinary students
      and residents. Technical deviations were overall more common after TR than pLFS,
      and in limbs repaired by students, regardless of procedure. The most difficult
      aspect of the TR consists of the bone tunnels whereas for pLFS it was passing the
      suture around the femorofabellar ligament. The sensitivity of radiographs for
      detection of technical deviations was 39% after TR and 50% after pLFS.
      CONCLUSION: Technical deviations are more common during the training phase of TR
      than pLFS, and the sensitivity of radiographs to detect those is low. Repeated
      practice on cadavers followed by dissection is recommended before use in
      patients.

PMID- 24433401
TI  - Analyzing the human liver vascular architecture by combining vascular corrosion
      casting and micro-CT scanning: a feasibility study.
AB  - Although a full understanding of the hepatic circulation is one of the keys to
      successfully perform liver surgery and to elucidate liver pathology, relatively
      little is known about the functional organization of the liver vasculature.
      Therefore, we materialized and visualized the human hepatic vasculature at
      different scales, and performed a morphological analysis by combining vascular
      corrosion casting with novel micro-computer tomography (CT) and image analysis
      techniques. A human liver vascular corrosion cast was obtained by simultaneous
      resin injection in the hepatic artery (HA) and portal vein (PV). A high
      resolution (110 MUm) micro-CT scan of the total cast allowed gathering detailed
      macrovascular data. Subsequently, a mesocirculation sample (starting at
      generation 5; 88 * 68 * 80 mm3) and a microcirculation sample (terminal vessels
      including sinusoids; 2.0 * 1.5 * 1.7 mm3) were dissected and imaged at a 71-MUm
      and 2.6-MUm resolution, respectively. Segmentations and 3D reconstructions
      allowed quantifying the macro- and mesoscale branching topology, and geometrical
      features of HA, PV and hepatic venous trees up to 13 generations (radii ranging
      from 13.2 mm to 80 MUm; lengths from 74.4 mm to 0.74 mm), as well as
      microvascular characteristics (mean sinusoidal radius of 6.63 MUm). Combining
      corrosion casting and micro-CT imaging allows quantifying the branching topology
      and geometrical features of hepatic trees using a multiscale approach from the
      macro- down to the microcirculation. This may lead to novel insights into liver
      circulation, such as internal blood flow distributions and anatomical
      consequences of pathologies (e.g. cirrhosis). 

PMID- 24433402
TI  - Imaging of Mohs micrographic surgery sections using full-field optical coherence
      tomography: a pilot study.
AB  - BACKGROUND: Full-field optical coherence tomography (FF-OCT) is a new noninvasive
      imaging technique that can see down to the cellular level without tissue
      preparation or contrast agents. OBJECTIVE: To use FF-OCT to image Mohs
      micrographic surgery specimens and verify the ability of a dermatopathologist to
      identify or exclude malignancy. MATERIALS AND METHODS: Two Mohs surgeons supplied
      18 Mohs sections from 11 patients. Each section was scanned using the FF-OCT, and
      a dermatopathologist blinded to the diagnosis examined the images for malignancy.
      The FF-OCT images were then compared with the intraoperative hematoxylin and
      eosin (H&E)-stained frozen sections for concordance. RESULTS: All 9 FF-OCT images
      interpreted as negative for malignancy were in agreement with the H&E frozen
      sections. Six of the remaining FF-OCT images were correctly interpreted as
      positive for malignancy, and three were deferred because malignancy could not be
      confirmed or excluded. CONCLUSION: Malignancy in Mohs sections can correctly be
      identified or excluded using FF-OCT. Although not ready for clinical use in its
      current state, FF-OCT has the potential to be incorporated into the Mohs workflow
      in the future.

PMID- 24433403
TI  - Lipid, adipokine and ghrelin levels in myocardial infarction patients with
      insulin resistance.
AB  - BACKGROUND: Insulin resistance (IR) is a risk factor for ischaemic heart disease
      and myocardial infarction (MI). IR often manifests in MI and is regarded as an
      independent predictor of in-hospital mortality, which can provide early risk
      stratification for recurrent acute coronary events. METHODS: The study enrolled
      200 patients (130 males and 70 females aged 61.4 +/- 1.12 years) diagnosed with
      ST elevation MI. At days 1 and 12 from the MI onset, IR levels and lipid
      profiles, as well as serum glucose, insulin, adipokine and ghrelin levels, were
      measured. RESULTS: Free fatty acid (FFA) levels had the most pronounced changes:
      IR patients had a 9-fold increase in FFA levels at day 1, and patients without IR
      had a 6-fold increase. Leptin levels at days 1 and 12, in IR patients were, on
      average, 1.5- and 2-fold higher compared to the controls and patients with no IR
      (r < 0.05). Leptin levels in IR patients were increased throughout the entire
      hospital stay. Resistin levels in IR patients were, on average, 1.4-fold higher
      throughout the entire hospital stay, while in non-IR patients, resistin levels
      were similar to the controls. Adiponectin levels in IR patients were decreased
      compared to the controls, while in patients with IR, they were similar to the
      controls. Both IR and non-IR MI patients had 3-fold and 3.7-fold lower ghrelin
      levels at day 1, respectively, compared to the controls. The correlation analysis
      showed a negative correlation between ghrelin and FFA (r = -0.48 r = 0.007),
      ghrelin and leptin (r = -0.4 r = 0.003), ghrelin and insulin (r = -0.54 r =
      0.002), and ghrelin and glucose (r = -0.31 r = 0.002) in MI patients. CONCLUSION:
      Dyslipidaemia, along with insulinaemia and glycaemia, is one of the most
      significant IR risk factors in the acute and early recovery phases of MI.
      Dyslipidaemia is characterised by a high FFA level; an imbalance of leptin,
      resistin, and adiponectin; and a deficiency of ghrelin in the acute and early
      recovery periods of MI. FFA and ghrelin can be used as promising molecular
      markers to stratify the risk of recurrent acute coronary events and diabetes
      mellitus in MI patients.

PMID- 24433404
TI  - MEFV gene mutations and cardiac phenotype in children with familial Mediterranean
      fever: a cohort study.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is the most common
      autoinflammatory disorder in the world. It is characterized by recurrent febrile
      inflammatory attacks of serosal and synovial membranes. MEFV gene mutations are
      responsible for the disease and its protein product, pyrin or marenostrin, plays
      an essential role in the regulation of the inflammatory reactions. Although the
      disease may carry a potential for cardiovascular disorders because of sustained
      inflammation during its course, the spectrum of cardiac involvement in children
      with FMF has not been well studied. We aimed at defining the frequency and
      spectrum of cardiac affection in children with FMF. The correlation between these
      affections and MEFV gene mutations was searched for to establish the relationship
      between cardiac phenotype and the patient's genotype in FMF. METHODS: The present
      work is a cohort study including 55 patients with the clinical diagnosis of FMF
      based on the Tel-Hashomere criteria, confirmed by genetic analysis showing
      homozygous or compound heterozygous mutation of MEFV genes. Fifty age- and sex
      matched normal children were included as controls. The entire study group
      underwent detailed cardiac examination, 12-lead ECG and echocardiography. All
      data was statistically analysed using SPSS version-15. RESULTS: Patients had an
      average age of 8.5+/-4.2 years; with an average disease duration of 2.1+/-2.2
      years; 28 were males. All controls showed no MEVF gene mutations. The most
      frequent gene mutation of the studied cases was E148Q mutation seen in 34% of
      cases and the most frequent compound mutation was E148Q/V726A seen in 16.6% of
      cases. Echocardiographic examination revealed pericardial effusion in nine
      patients. Twelve had aortic regurgitation; nine had mitral regurgitation and six
      had pulmonary regurgitation. The most common mutation associated with pericardial
      effusion was E148Q/V726A in 5/9 of cases. Valvular involvement were significantly
      more common in FMF patients with gene mutations. Also cardiac involvement was
      more common in patients with positive consanguinity. However, these cardiac
      manifestations showed no correlation to age, family history of FMF, or response
      to therapy or laboratory data. CONCLUSIONS: In our cohort of children with FMF,
      cardiac involvement appears to be common. Pericardial effusions are significantly
      related to presence of mutation types E48Q, P 369S, V726A. These associations may
      warrant genetic screening of children with FMF to detect cardiac risk.

PMID- 24433405
TI  - Single-nucleotide variations defining previously unreported ADAMTS13 haplotypes
      are associated with differential expression and activity of the VWF-cleaving
      protease in a Salvadoran congenital thrombotic thrombocytopenic purpura family.

PMID- 24433406
TI  - Ecological drivers of antipredator defenses in carnivores.
AB  - Mammals have evolved several morphological and behavioral adaptations to reduce
      the risk of predation, but we know little about the ecological factors that favor
      their evolution. For example, some mammalian carnivores have the ability to spray
      noxious anal secretions in defense, whereas other species lack such weaponry but
      may instead rely on collective vigilance characteristic of cohesive social
      groups. Using extensive natural history data on 181 species in the order
      Carnivora, we created a new estimate of potential predation risk from mammals and
      birds of prey and used comparative phylogenetic methods to assess how different
      sources of predation risk and other ecological variables influence the evolution
      of either noxious weaponry or sociality in this taxon. We demonstrate that the
      evolution of enhanced spraying ability is favored by increased predation risk
      from other mammals and by nocturnality, but the evolution of sociality is favored
      by increased predation risk from birds of prey and by diurnality, which may allow
      for enhanced early visual detection. These results suggest that noxious defenses
      and sociality are alternative antipredator strategies targeting different
      predator guilds under different lighting conditions. 

PMID- 24433408
TI  - Prevalence and severity of anemia among school children in Jimma Town, Southwest
      Ethiopia.
AB  - BACKGROUND: Anemia is a major health problem worldwide. Because of health and
      socioeconomic problems, the prevalence of anemia is higher in developing
      countries. Children and pregnant women are the most vulnerable groups to anemia.
      The aim of the present study was to determine the magnitude of anemia among
      school children. METHODS: A cross-sectional household survey was conducted in
      January 2011 on 423 children, aged 6-14 years, selected through systematic random
      sampling method. Sociodemographic and anthropometric data were collected using a
      pre-tested questionnaire. Capillary blood was taken from the fingertip of each
      child and hemoglobin was measured using HaemoCue digital photometer. All the
      necessary safety measures were taken during blood collection. Anthropometric
      indicators were measured using WHO's guideline. Data analysis was made using SPSS
      Version 16.0 for Windows. The association between predictors and outcome
      variables were measured by a stepwise logistic regression model. Ethical
      permission was obtained; consent of the parents/guardian was taken and
      confidentiality was maintained. RESULT: A total of 404 children were studied. The
      mean age was 10.21(SD +/- 1.89) years. The proportion of females was 217(53.7%).
      The mean hemoglobin level for both sexes was 11.59(SD +/- 1.97 g/dl). The current
      prevalence of anemia was 152(37.6%), out of which, 73(18.1%) had mild while
      79(19.6%) of them had moderate anemia. The prevalence of anemia among the age
      group of 6-11 years was 118(40.5%) while the prevalence among the group of 12-14
      years old children was 34(30.1%). Among the selected variables in the logistic
      regression analysis, low family income [OR = 4.925, 95% CI(1.063,22.820)],
      mothers' education [OR = 4.621, 95% CI(1.383,15.439)], intake of plant food [OR =
      3.847, 95% CI(2.068, 7.157)] and intake of animal food [OR = 2.37, 95%
      CI(1.040,5.402)] were significantly and independently associated with anemia.
      CONCLUSION: Anemia is a moderate public health problem in the study area. Family
      income, educational status of parents and inadequate plant and animal food intake
      are the predictors of anemia. Improving the economic status of the family, women
      education and health education about balanced animal and plant food consumption
      are recommended strategies to reduce the burden of anemia.

PMID- 24433409
TI  - Aging Cell: open access to all.

PMID- 24433410
TI  - Long term outcome after laser assisted modified Forssell's in cribbing horses.
AB  - OBJECTIVE: To (1) report long-term outcome after laser assisted modified
      Forssell's procedure; (2) describe the prevalence of postoperative complications;
      and (3) identify risk factors associated with outcome. STUDY DESIGN:
      Retrospective case series. ANIMALS: Horses (n = 119). METHODS: Medical records
      (1994-2012) of horses that had laser assisted modified Forssell's procedure were
      reviewed. Signalment, preoperative duration of cribbing, postoperative
      complications and outcome were recorded. RESULTS: Follow-up was available for 90
      horses; 76 had stopped cribbing for >1 year. Of 14 horses that resumed cribbing,
      median relapse time was 6 months. Preoperative cribbing duration was
      significantly associated with an increased probability of unsuccessful outcome
      when horses cribbed for >3 years before surgery (odds ratio of positive outcome:
      OR = 0.14, 95% CI: 0.02, 0.95). Overall, 22.2% horses had postoperative
      complications (hematoma, seroma, infection, and prolonged drainage). CONCLUSIONS:
      Laser assisted modified Forssell's is a very effective (84.4%) surgical treatment
      of cribbing behavior in horses. Preoperative cribbing duration was identified as
      a significant risk factor associated with unsuccessful surgical outcome.

PMID- 24433411
TI  - Influence of covariate distribution on the predictive performance of
      pharmacokinetic models in paediatric research.
AB  - AIMS: The accuracy of model-based predictions often reported in paediatric
      research has not been thoroughly characterized. The aim of this exercise is
      therefore to evaluate the role of covariate distributions when a pharmacokinetic
      model is used for simulation purposes. METHODS: Plasma concentrations of a
      hypothetical drug were simulated in a paediatric population using a
      pharmacokinetic model in which body weight was correlated with clearance and
      volume of distribution. Two subgroups of children were then selected from the
      overall population according to a typical study design, in which pre-specified
      body weight ranges (10-15 kg and 30-40 kg) were used as inclusion criteria. The
      simulated data sets were then analyzed using non-linear mixed effects modelling.
      Model performance was assessed by comparing the accuracy of AUC predictions
      obtained for each subgroup, based on the model derived from the overall
      population and by extrapolation of the model parameters across subgroups.
      RESULTS: Our findings show that systemic exposure as well as pharmacokinetic
      parameters cannot be accurately predicted from the pharmacokinetic model obtained
      from a population with a different covariate range from the one explored during
      model building. Predictions were accurate only when a model was used for
      prediction in a subgroup of the initial population. CONCLUSIONS: In contrast to
      current practice, the use of pharmacokinetic modelling in children should be
      limited to interpolations within the range of values observed during model
      building. Furthermore, the covariate point estimate must be kept in the model
      even when predictions refer to a subset different from the original population.

PMID- 24433413
TI  - Computer applications making rapid advances in high throughput microbial
      proteomics (HTMP).
AB  - The last few decades have seen the rise of widely-available proteomics tools.
      From new data acquisition devices, such as MALDI-MS and 2DE to new database
      searching softwares, these new products have paved the way for high throughput
      microbial proteomics (HTMP). These tools are enabling researchers to gain new
      insights into microbial metabolism, and are opening up new areas of study, such
      as protein-protein interactions (interactomics) discovery. Computer software is a
      key part of these emerging fields. This current review considers: 1) software
      tools for identifying the proteome, such as MASCOT or PDQuest, 2) online
      databases of proteomes, such as SWISS-PROT, Proteome Web, or the Proteomics
      Facility of the Pathogen Functional Genomics Resource Center, and 3) software
      tools for applying proteomic data, such as PSI-BLAST or VESPA. These tools allow
      for research in network biology, protein identification, functional annotation,
      target identification/validation, protein expression, protein structural
      analysis, metabolic pathway engineering and drug discovery. 

PMID- 24433412
TI  - Predictors and moderators of outcomes of HIV/STD sex risk reduction interventions
      in substance abuse treatment programs: a pooled analysis of two randomized
      controlled trials.
AB  - BACKGROUND: The objective of the current study was to examine predictors and
      moderators of response to two HIV sexual risk interventions of different content
      and duration for individuals in substance abuse treatment programs. METHODS:
      Participants were recruited from community drug treatment programs participating
      in the National Institute on Drug Abuse Clinical Trials Network (CTN). Data were
      pooled from two parallel randomized controlled CTN studies (one with men and one
      with women) each examining the impact of a multi-session motivational and skills
      training program, in comparison to a single-session HIV education intervention,
      on the degree of reduction in unprotected sex from baseline to 3- and 6- month
      follow-ups. The findings were analyzed using a zero-inflated negative binomial
      (ZINB) model. RESULTS: Severity of drug use (p < .01), gender (p < .001), and age
      (p < .001) were significant main effect predictors of number of unprotected
      sexual occasions (USOs) at follow-up in the non-zero portion of the ZINB model
      (men, younger participants, and those with greater severity of drug/alcohol abuse
      have more USOs). Monogamous relationship status (p < .001) and race/ethnicity (p
      < .001) were significant predictors of having at least one USO vs. none
      (monogamous individuals and African Americans were more likely to have at least
      one USO). Significant moderators of intervention effectiveness included recent
      sex under the influence of drugs/alcohol (p < .01 in non-zero portion of model),
      duration of abuse of primary drug (p < .05 in non-zero portion of model), and
      Hispanic ethnicity (p < .01 in the zero portion, p < .05 in the non-zero portion
      of model). CONCLUSION: These predictor and moderator findings point to ways in
      which patients may be selected for the different HIV sexual risk reduction
      interventions and suggest potential avenues for further development of the
      interventions for increasing their effectiveness within certain subgroups.

PMID- 24433414
TI  - Comparative analysis of RNAi screening technologies at genome-scale reveals an
      inherent processing inefficiency of the plasmid-based shRNA hairpin.
AB  - RNAi screening in combination with the genome-sequencing projects would
      constitute the Holy Grail of modern genetics; enabling discovery and validation
      towards a better understanding of fundamental biology leading to novel targets to
      combat disease. Hit discordance at inter-screen level together with the lack of
      reproducibility is emerging as the technology's main pitfalls. To examine some of
      the underlining factors leading to such discrepancies, we reasoned that perhaps
      there is an inherent difference in knockdown efficiency of the various RNAi
      technologies. For this purpose, we utilized the two most popular ones, chemically
      synthesized siRNA duplex and plasmid-based shRNA hairpin, in order to perform a
      head to head comparison. Using a previously developed gain-of-function assay
      probing modulators of the miRNA biogenesis pathway, we first executed on a siRNA
      screen against the Silencer Select V4.0 library (AMB) nominating 1,273, followed
      by an shRNA screen against the TRC1 library (TRC1) nominating 497 gene
      candidates. We observed a poor overlap of only 29 hits given that there are
      15,068 overlapping genes between the two libraries; with DROSHA as the only
      common hit out of the seven known core miRNA biogenesis genes. Distinct genes
      interacting with the same biogenesis regulators were observed in both screens,
      with a dismal cross-network overlap of only 3 genes (DROSHA, TGFBR1, and DIS3).
      Taken together, our study demonstrates differential knockdown activities between
      the two technologies, possibly due to the inefficient intracellular processing
      and potential cell-type specificity determinants in generating intended targeting
      sequences for the plasmid-based shRNA hairpins; and suggests this observed
      inefficiency as potential culprit in addressing the lack of reproducibility. 

PMID- 24433416
TI  - Heparin increasing podocyte-specific gene expressions.
AB  - AIM: Heparin, a highly sulfated glycosaminoglycan, has been shown to have a
      renoprotective effect on renal diseases, but its mechanisms remain to be
      elucidated. In this study, we examined the effect of heparin on podocytes by
      using primary cultured podocytes positive for podocyte-specific markers including
      podocin and podocalyxin. METHODS: Podocytes were cultured from highly purified
      glomeruli isolated by the method with renal perfusion with magnetic beads and
      digestion of collagenase. Podocyte-specific gene expressions and proteins were
      examined by real-time polymerase chain reaction (PCR), Western blotting and
      immunofluorescence microscopy. RESULTS: Real-time PCR showed that addition of
      heparin to the culture media significantly upregulated most of the podocyte
      specific genes in a dose-dependent and time-dependent manner. Western blotting
      showed a marked increase in protein levels of nephrin and podocin. Podocin
      localization at cell-cell contact sites became conspicuous in the presence of
      heparin. The effect of heparin was observed even in culture media deprived of
      bovine foetal serum. Heparan sulfate, less sulfated than heparin, and hyaluronan
      did not show such effects, but sulfated dextran did markedly. CONCLUSION: Heparin
      acts on cultured podocytes to increase podocyte-specific gene expressions. A high
      degree of sulfation is crucial for the effect of heparin.

PMID- 24433417
TI  - Osteoarthritis of the knee or hip significantly impairs driving ability (cross
      sectional survey).
AB  - BACKGROUND: Advising patients about when they can drive after surgery is common
      practice after arthroplasty of the knee or hip. In the literature, the
      preoperative braking performance values of the patients are frequently taken as
      the "safe" landmark. We hypothesised that osteoarthritis (OA), the most frequent
      reason for arthroplasty, already compromises the ability to perform an emergency
      stop. We expected that both Reaction Time (RT) and Movement Time (MT) as
      components of the Total Brake Response Time (TBRT), would be prolonged in
      patients with OA of the knee or hip in comparison with healthy subjects. We also
      expected maximum pressure levels on the brake pedal to be reduced in such cases.
      METHODS: A real car cabin was equipped with pressure sensors on the accelerator
      and brake pedals to measure RT, MT, TBRT and maximum Brake Force (BF) under
      realistic spatial constraints. Patients with OA of the knee (right n = 18, left n
      = 15) or hip (right n = 20, left n = 19) were compared with a healthy control
      group (n = 21). RESULTS: All measured values for TBRT in the control group
      remained below 600 ms. OA of the right hip or knee significantly prolonged the
      braking performance (right hip: TBRT p = 0.025, right knee: TBRT p < 0.001),
      whereas OA of the left hip did not impair driving ability (TBRT p = 0.228).
      Intriguingly, OA of the left knee prolonged RT and MT to the same degree as OA on
      the contralateral side (RT p = 0.001, MT p < 0.001). CONCLUSIONS: This study
      demonstrates that depending on the localisation of OA, driving capability can be
      impaired; OA can significantly increase the total braking distance. To ensure
      safe traffic participation the safety margin for TBRT should be strictly set,
      under our experimental conditions, at around 600 ms. Moreover, therapeutic
      approaches to OA, such as physiotherapy, and patients receiving surgery of the
      left knee should take into account that left knee OA can also impair driving
      ability. TRIAL REGISTRATION:  CLINICAL TRIAL REGISTRATION NUMBER: Project number
      of the ethics committee of the University of Tubingen: 268/2009BO2; 267/2009BO2.

PMID- 24433418
TI  - Improved population level survival in younger Hodgkin lymphoma patients in
      Germany in the early 21st century.
AB  - Treatment for Hodgkin lymphoma (HL) is more aggressive in Germany than in the
      United States (US) and differences in treatment may lead to differences in
      population level survival. Patients diagnosed with HL in 11 German states in 1997
      2006 were included in the analyses and were compared to similar analyses from
      patients in the Surveillance, Epidemiology, and End Results database in the US.
      Period analysis was used to calculate 5-year relative survival for the time
      period of 2002-2006 overall and by gender, age and histology. Overall 5-year
      relative survival for patients with HL in Germany was 84.3%, compared to 80.6%
      for the US. Survival was highest in patients aged 15-29 years at 97.9% and
      decreased with age to 57.5% at age 60 + Survival for men and women, respectively,
      was 84.7% and 84.1% in Germany and 78.2% and 83.6% in the US. 5-year relative
      survival for patients diagnosed with HL in Germany was close to 100% for younger
      patients. Survival of HL patients in the US was lower than in Germany overall,
      but was comparable in older patients and in women. Population-based studies with
      longer follow-up are still needed to examine effects of late toxicity on long
      term survival.

PMID- 24433420
TI  - Hot melt extrusion - processing solid solutions?

PMID- 24433419
TI  - A cross-sectional study of stand-alone percutaneous coronary intervention in a
      Nigerian cardiac catheterization laboratory.
AB  - BACKGROUND: There is a paucity of diagnostic and therapeutic facilities in
      Nigeria to confirm coronary artery disease and offer appropriate interventional
      therapy. There is now a private cardiac catheterization laboratory in Lagos but
      as there are no sustained Open Heart Surgery programmes, percutaneous coronary
      interventions are currently being performed without surgical backup. This study
      was designed to assess results of stand-alone percutaneous coronary intervention
      (PCI) as currently practiced in Lagos, Nigeria. METHODS: This cross-sectional
      study was conducted between July 2009 and July 2012. The study included all
      patients that underwent PCI in Lagos. Data was extracted from a prospectively
      maintained database. RESULTS: Coronary artery disease was confirmed in 80 (52.6%)
      of 152 Nigerians referred with a diagnosis of Ischaemic Heart Disease. There were
      53 males (66.2%) and 27 females (33.8%). The average age was 60.3 +/-9.6 years
      and average euroscore was 4.5 +/-3.1. Of the 80 patients, 77 (96.3%) had
      significant stenoses and were candidates for revascularization. Distribution of
      significant stenoses was one in 32 patients (41.5%), two in 11 patients (14.3%),
      three in 19 patients (24.7%), four in 13 patients (16.9%) and five in 2 patients
      (2.6%). PCI was performed in 48 (62.3%) of the patients eligible for
      revascularization as the coronary anatomy in the remaining patients was not
      suitable for PCI. The indication for PCI was for myocardial infarction or
      unstable angina in 39 patients (81.2%). PCI was performed with PTCA plus stenting
      in 41 patients (85.4%) and with PTCA alone in 7 patients (14.6%) with good
      angiographic results. Overall 29 of the 48 patients (60.4%) had complete
      revascularization of significant stenoses. Complications of PCI were bleeding
      that required blood transfusion in 1 patient (2.1%), minor femoral haematomas in
      2 patients (4.2%), and a major adverse clinical event in 1 patient (2.1%).
      CONCLUSION: A stand-alone PCI programme has been developed in Lagos, Nigeria.
      Both elective and urgent PCIs have been performed with no mortalities and a low
      complication rate. Increased volumes will however accrue and complete
      revascularization rates would be improved with the establishment of Open Heart
      Surgery programmes to provide CABG as back-up for PCI and alternate therapy for
      more complex lesions.

PMID- 24433421
TI  - Hot-melt co-extrusion: requirements, challenges and opportunities for
      pharmaceutical applications.
AB  - OBJECTIVES: Co-extrusion implies the simultaneous hot-melt extrusion of two or
      more materials through the same die, creating a multi-layered extrudate. It is an
      innovative continuous production technology that offers numerous advantages over
      traditional pharmaceutical processing techniques. This review provides an
      overview of the co-extrusion equipment, material requirements and medical and
      pharmaceutical applications. KEY FINDINGS: The co-extrusion equipment needed for
      pharmaceutical production has been summarized. Because the geometrical design of
      the die dictates the shape of the final product, different die types have been
      discussed. As one of the major challenges at the moment is shaping the final
      product in a continuous way, an overview of downstream solutions for processing
      co-extrudates into drug products is provided. Layer adhesion, extrusion
      temperature and viscosity matching are pointed out as most important requirements
      for material selection. Examples of medical and pharmaceutical applications are
      presented and some recent findings considering the production of oral drug
      delivery systems have been summarized. SUMMARY: Co-extrusion provides great
      potential for the continuous production of fixed-dose combination products which
      are gaining importance in pharmaceutical industry. There are still some barriers
      to the implementation of co-extrusion in the pharmaceutical industry. The
      optimization of downstream processing remains a point of attention.

PMID- 24433422
TI  - Process monitoring and visualization solutions for hot-melt extrusion: a review.
AB  - OBJECTIVES: Hot-melt extrusion (HME) is applied as a continuous pharmaceutical
      manufacturing process for the production of a variety of dosage forms and
      formulations. To ensure the continuity of this process, the quality of the
      extrudates must be assessed continuously during manufacturing. The objective of
      this review is to provide an overview and evaluation of the available process
      analytical techniques which can be applied in hot-melt extrusion. KEY FINDINGS:
      Pharmaceutical extruders are equipped with traditional (univariate) process
      monitoring tools, observing barrel and die temperatures, throughput, screw speed,
      torque, drive amperage, melt pressure and melt temperature. The relevance of
      several spectroscopic process analytical techniques for monitoring and control of
      pharmaceutical HME has been explored recently. Nevertheless, many other sensors
      visualizing HME and measuring diverse critical product and process parameters
      with potential use in pharmaceutical extrusion are available, and were thoroughly
      studied in polymer extrusion. The implementation of process analytical tools in
      HME serves two purposes: (1) improving process understanding by monitoring and
      visualizing the material behaviour and (2) monitoring and analysing critical
      product and process parameters for process control, allowing to maintain a
      desired process state and guaranteeing the quality of the end product. SUMMARY:
      This review is the first to provide an evaluation of the process analytical tools
      applied for pharmaceutical HME monitoring and control, and discusses techniques
      that have been used in polymer extrusion having potential for monitoring and
      control of pharmaceutical HME.

PMID- 24433423
TI  - Investigation of process temperature and screw speed on properties of a
      pharmaceutical solid dispersion using corotating and counter-rotating twin-screw
      extruders.
AB  - OBJECTIVE: The use of corotating twin screw hot-melt extruders to prepare
      amorphous drug/polymer systems has become commonplace. As small molecule drug
      candidates exiting discovery pipelines trend towards higher MW and become more
      structurally complicated, the acceptable operating space shifts below the drug
      melting point. The objective of this research is to investigate the extrusion
      process space, which should be selected to ensure that the drug is solubilized in
      the polymer with minimal thermal exposure, is critical in ensuring the
      performance, stability and purity of the solid dispersion. METHODS: The
      properties of a model solid dispersion were investigated using both corotating
      and counter-rotating hot-melt twin-screw extruders operated at various
      temperatures and screw speeds. The solid state and dissolution performance of the
      resulting solid dispersions was investigated and evaluated in context of
      thermodynamic predictions from Flory-Huggins Theory. In addition, the residence
      time distributions were measured using a tracer, modelled and characterized. KEY
      FINDINGS: The amorphous content in the resulting solid dispersions was dependent
      on the combination of screw speed, temperature and operating mode. CONCLUSIONS:
      The counter-rotating extruder was observed to form amorphous solid dispersions at
      a slightly lower temperature and with a narrower residence time distribution,
      which also exhibited a more desirable shape.

PMID- 24433424
TI  - Investigation into mixing capability and solid dispersion preparation using the
      DSM Xplore Pharma Micro Extruder.
AB  - OBJECTIVES: The goal of this investigation was to qualify the DSM Xplore Pharma
      Micro Extruder as a formulation screening tool for early-stage hot-melt
      extrusion. METHODS: Dispersive and distributive mixing was investigated using
      soluplus, copovidone or basic butylated methacrylate copolymer with sodium
      chloride (NaCl) in a batch size of 5 g. Eleven types of solid dispersions were
      prepared using various drugs and carriers in batches of 5 g in accordance with
      the literature. KEY FINDINGS: The dispersive mixing was a function of screw speed
      and recirculation time and the particle size was remarkably reduced after 1 min
      of processing, regardless of the polymers. An inverse relationship between the
      particle size and specific mechanical energy (SME) was also found. The SME values
      were higher than those in large-scale extruders. After 1 min recirculation at 200
      rpm, the uniformity of NaCl content met the criteria of the European
      Pharmacopoeia, indicating that distributive mixing was achieved in this time. For
      the solid dispersions preparations, the results from different scanning
      calorimetry, powder X-ray diffractometry and in-vitro dissolution tests confirmed
      that all solid-dispersion systems were successfully prepared. CONCLUSIONS: These
      findings demonstrated that the extruder is a useful tool to screen solid
      dispersion formulations and their material properties on a small scale.

PMID- 24433425
TI  - Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous
      solid dispersions.
AB  - OBJECTIVES: The development of amorphous solid dispersions is of increasing
      interest in the delivery of bioactive compounds; however, there is a need for a
      methodology that enables the rational selection of polymers for solid dispersion
      formulations with optimal stability to crystallization. The objective of this
      study was to evaluate the use of mid-infrared (IR) spectroscopy for this purpose.
      METHODS: Polymers evaluated included poly(vinylpyrrolidone) (PVP), Eudragit E100
      (E100), carboxymethylcellulose acetate butyrate (CMCAB),
      hydroxypropylmethylcellulose (HPMC), HPMC acetate succinate (HPMCAS) and
      poly(acrylic acid) (PAA). Model crystalline bioactive polyphenols included
      quercetin and naringenin. Amorphous solid dispersions were prepared by dissolving
      both polyphenol and polymer in a common solvent followed by solvent evaporation.
      Mid-IR spectroscopy was used to determine and quantify the extent of polyphenol
      polymer interactions, and powder X-ray diffraction was used to monitor physical
      stability following storage at different environmental conditions. KEY FINDINGS:
      The mid-IR analysis suggested the following rank order for the crystallization
      inhibiting performance of the different polymers: E100 > PVP > HPMCAS > HPMC >=
      CMCAB > PAA. The initial performance of the different polymers was evaluated
      using the highest concentration of polyphenol for which x-ray amorphous solid
      dispersions could be prepared via rotary evaporation. The observed stability
      followed that predicted from the mid-infrared spectroscopy evaluation of
      intermolecular interactions. The dispersions with better polyphenol-polymer
      interactions were stable against crystallization when exposed to high relative
      humidity and high temperatures; on the other hand, systems that had weak
      interactions were not stable to crystallization when stored at moderate
      environmental conditions. CONCLUSIONS: Based on the observed ability of mid-IR
      analysis to enable the characterization of intermolecular polyphenol-polymer
      interactions and based on the correlation between the extent of intermolecular
      interactions and the crystallization-inhibiting performance of polymers, it can
      be concluded that this technique is an important tool for the rational
      formulation of solid dispersions with optimized physical stability.

PMID- 24433426
TI  - A comparative study of the effect of spray drying and hot-melt extrusion on the
      properties of amorphous solid dispersions containing felodipine.
AB  - OBJECTIVES: To compare the properties of solid dispersions of felodipine for oral
      bioavailability enhancement using two different polymers, polyvinylpyrrolidone
      (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt
      extrusion (HME) and spray drying. METHODS: Felodipine solid dispersions were
      prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer
      matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed
      characterization was performed using differential scanning calorimetry, powder X
      ray diffractometry, scanning electron microscopy and in-vitro dissolution
      testing. Dissolution profiles were evaluated in the presence of sodium dodecyl
      sulphate. Stability of different solid dispersions was studied under accelerated
      conditions (40 degrees C/75% RH) over 8 weeks. KEY FINDINGS: Spray-dried
      formulations were found to release felodipine faster than melt extruded
      formulations for both polymer matrices. Solid dispersions containing HMPCAS
      exhibited higher drug release rates and better wettability than those produced
      with a PVP matrix. No significant differences in stability were observed except
      with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried
      formulations. CONCLUSIONS: Solid dispersions of felodipine produced by spray
      drying exhibited more rapid drug release than corresponding melt extruded
      formulations, although in some cases improved stability was observed for melt
      extruded formulations.

PMID- 24433427
TI  - The utilization of drug-polymer interactions for improving the chemical stability
      of hot-melt extruded solid dispersions.
AB  - OBJECTIVE: Interactions between drugs and polymers were utilized to lower the
      processing temperature of hot-melt extrusion (HME), and thus minimize the thermal
      degradation of heat-sensitive drugs during preparation of amorphous solid
      dispersions. METHODS: Diflunisal (DIF), which would degrade upon melting, was
      selected as a model drug. Hydrogen bonds between DIF and polymeric carriers (PVP
      K30, PVP VA64, hydroxypropyl methylcellulose and Soluplus) were revealed by
      differential scanning calorimetry and Fourier transform infrared spectroscopy.
      The hot-melt extruded solid dispersion was characterized by powder X-ray
      diffraction (XRD), scanning electron microscopy (SEM) and high-performance liquid
      chromatography (HPLC). KEY FINDINGS: The results of hot-stage polar microscopy
      indicated that DIF was dissolved in molten polymers at 160 degrees C, much lower
      than the melting point of DIF (215 degrees C). At this temperature, amorphous
      solid dispersions were successfully produced by HME, as confirmed by XRD and SEM.
      The related impurities in amorphous solid dispersions detected by HPLC were lower
      than 0.3%, indicating that thermal degradation was effectively minimized. The
      dissolution of DIF from amorphous solid dispersions was significantly enhanced as
      compared with the pure crystalline drug. CONCLUSION: This technique based on drug
      polymer interactions to prepare chemically stable amorphous solid dispersions by
      HME provides an attractive opportunity for development of heat-sensitive drugs.

PMID- 24433428
TI  - Effect of plasticiser type on the hot melt extrusion of venlafaxine
      hydrochloride.
AB  - OBJECTIVES: During hot melt extrusion (HME), phase changes and interactions due
      to thermo-mechanical stresses affect the drug incorporation into polymeric
      matrices. Two HME compositions of venlafaxine HCl with Eudragit RSPO (Evonic,
      Darmstadt, Germany) as the matrix polymer and either citric acid monohydrate
      (CAMH) or Lutrol F127 (BASF, Ludwigshafen, Germany) as plasticisers were
      compared. METHODS: Miscibility and extrusion temperatures were elucidated based
      on solubility parameters and differential scanning calorimetry. Thermal changes
      in the extruded melts and their respective physical mixtures were compared.
      Powder X-ray diffraction was applied to detect changes in crystallinity and
      fourier transform infrared (FT-IR) spectroscopy for chemical interactions. KEY
      FINDINGS: Both plasticisers (15%) enabled extrusion easily. With Lutrol, the drug
      remained crystalline, whereas with CAMH a single-phase amorphous transparent
      extrudate was obtained. Differences between the thermographs of extruded and
      physical mixtures indicated the importance of mechanical stresses in the single
      screw extruder. In the FT-IR spectrum of Eudragit/CAMH/drug extrudate, the
      abscence of the peak due to venlafaxine OH and the merging of the two peaks due
      to CAMH carbonyl, into one, indicated esterification. CONCLUSIONS: CAMH and
      Lutrol have different reactivities towards venlafaxine HCl and also different
      plasticising mechanisms for Eudragit RSPO because of hydrogen bonding and because
      of similar overall molecular attractive forces, respectively.

PMID- 24433429
TI  - Formulation optimization of hot-melt extruded abuse deterrent pellet dosage form
      utilizing design of experiments.
AB  - OBJECTIVE: The objective of this study was to develop techniques for an abuse
      deterrent (AD) platform utilizing the hot-melt extrusion (HME) process. METHODS:
      Formulation optimization was accomplished by utilizing Box-Behnken design of
      experiments to determine the effect of the three formulation factors: PolyOx
      WSR301, Benecel K15M and Carbopol 71G; each of which was studied at three levels
      on tamper-resistant (TR) attributes of the produced melt extruded pellets. A
      response surface methodology was utilized to identify the optimized formulation.
      Lidocaine hydrochloride was used as a model drug, and suitable formulation
      ingredients were employed as carrier matrices and processing aids. KEY FINDINGS:
      All of the formulations were evaluated for the TR attributes, such as particle
      size post-milling, gelling and percentage of drug extraction in water and
      alcohol. All of the design of experiments formulations demonstrated sufficient
      hardness and elasticity, and could not be reduced into fine particles (<150 MUm),
      which is a desirable feature to prevent snorting. In addition, all of the
      formulations exhibited good gelling tendency in water with minimal extraction of
      drug in the aqueous medium. Moreover, Benecel K15M, in combination with PolyOx
      WSR301, could be utilized to produce pellets with TR potential. CONCLUSION: HME
      has been demonstrated to be a viable technique with a potential to develop novel
      AD formulations.

PMID- 24433431
TI  - Changes in state prescription contraceptive mandates for insurers: the effect on
      women's contraceptive use.
AB  - CONTEXT: Access to effective contraceptives is critical to reducing levels of
      unintended childbearing in the United States. Since 1998, more than half the
      states have passed legislation requiring insurers that cover prescription drugs
      to cover prescription contraceptives approved by the Food and Drug
      Administration. An assessment of the impact of these laws on women's
      contraceptive use is needed to determine whether such policies are effective.
      METHODS: Information was collected on state contraceptive coverage policies, and
      contraceptive use data among women at risk of unintended pregnancy were drawn
      from Behavioral Risk Factor Surveillance System surveys conducted between 1998
      and 2010. Logit regression analysis was used to calculate the marginal effects of
      state contraceptive coverage laws on insured and uninsured women's use of
      prescription methods. RESULTS: Insured women who lived in a state with a
      contraceptive coverage law were 5% more likely than their counterparts in states
      without such laws to use an effective method (i.e., a prescription method,
      condoms or sterilization). Among women who used such methods, those in
      contraceptive coverage states were 5% more likely than women in other states to
      use any prescription method, and 4% more likely to use the pill. No associations
      were found between contraceptive mandates and method use by uninsured women.
      Among both users and nonusers, contraceptive coverage was associated with a 5%
      increase in pill use. CONCLUSIONS: Contraceptive coverage mandates appear to play
      a role in increasing the use of prescription contraceptives among insured women,
      and hence may help to reduce the numbers of unintended pregnancies.

PMID- 24433430
TI  - ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements
      for combination DMARDs and corticosteroids: secondary analysis of a randomized
      controlled trial.
AB  - INTRODUCTION: UK guidelines recommend that all early active rheumatoid arthritis
      (RA) patients are offered combination disease-modifying antirheumatic drugs
      (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody
      (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We
      used data from a randomized controlled trial - the Combination Anti-Rheumatic
      Drugs in Early RA (CARDERA) trial - to examine whether responses to intensive
      combination treatments in early RA differ by ACPA status. METHODS: The CARDERA
      trial randomized 467 early active RA patients to receive: (1) methotrexate, (2)
      methotrexate/ciclosporin, (3) methotrexate/prednisolone or (4)
      methotrexate/ciclosporin/prednisolone in a factorial-design. Patients were
      assessed every six months for two years. In this analysis we evaluated 431
      patients with available ACPA status. To minimize multiple testing we used a mixed
      effects repeated measures ANOVA model to test for an interaction between ACPA and
      treatment on mean changes from baseline for each outcome (Larsen, disease
      activity scores on a 28-joint count (DAS28), Health Assessment Questionnaire
      (HAQ), EuroQol, SF-36 physical component summary (PCS) and mental component
      summary (MCS) scores). When a significant interaction was present, mean changes
      in outcomes were compared by treatment group at each time point using t-tests
      stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with
      treatment were calculated stratified by ACPA. RESULTS: ACPA status influenced the
      need for combination treatments to reduce radiological progression. ACPA-positive
      patients had significant reductions in Larsen score progression with all
      treatments. ACPA-positive patients receiving triple therapy had the greatest
      benefits: two-year mean Larsen score increases comprised 3.66 (95% confidence
      interval (CI) 2.27 to 5.05) with triple therapy and 9.58 (95% CI 6.76 to 12.39)
      with monotherapy; OR for new erosions with triple therapy versus monotherapy was
      0.32 (95% CI 0.14 to 0.72; P = 0.003). ACPA-negative patients had minimal
      radiological progression irrespective of treatment. Corticosteroid's impact on
      improving DAS28/PCS scores was confined to ACPA-positive RA. CONCLUSIONS: ACPA
      status influences the need for combination DMARDs and high-dose tapering
      corticosteroids in early RA. In CARDERA, combination therapy was only required to
      prevent radiological progression in ACPA-positive patients; corticosteroids only
      provided significant disease activity and physical health improvements in ACPA
      positive disease. This suggests ACPA is an important biomarker for guiding
      treatment decisions in early RA. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN32484878.

PMID- 24433432
TI  - Craniomaxillofacial abnormalities in dogs with congenital palatal defects:
      computed tomographic findings.
AB  - OBJECTIVE: To evaluate craniomaxillofacial abnormalities in dogs with congenital
      palatal defects. STUDY DESIGN: Retrospective computed tomography (CT) study.
      ANIMALS: Dogs with congenital palatal defects (n = 9). METHODS: Medical records
      and CT reports (1995-2012) were searched for dogs with a diagnosis of cleft
      palate that had a CT study. Data retrieved were: breed, age, sex, weight,
      physical examination, and laboratory findings, number of previous palate
      surgeries, and oral/dental examination findings with the diagnosis of the cleft
      for each dog. CT studies of the head were reviewed on a structure-by-structure
      basis. RESULTS: Tympanic bullae were most commonly found to be abnormal (8 dogs),
      followed by nasal turbinates (6), nasal septum, vomer, cribriform plate (4),
      frontal sinuses, and lateral ventricles (3). Other abnormalities were related to
      occlusion, teeth, incisive bones, maxillary bones, mandibles, hyoid apparatus,
      cranial bones, and nasopharynx. The soft tissue defect of the cleft was always
      smaller than the bony defect. CONCLUSIONS: Craniomaxillofacial abnormalities in
      dogs with congenital palatal defects are common and some of these may negatively
      affect the quality of life. Importantly for surgical planning, the soft tissue
      component of the cleft may underestimate the extent of the bony defect,
      especially in failed repairs.

PMID- 24433433
TI  - Dynamic observation of artery endothelial cell layers in response to bare metal
      stent and paclitaxel-eluting stent in vitro.
AB  - OBJECTIVES: We aimed to investigate the mechanism of paclitaxel-eluting stent
      (PES) induced thrombosis by real-time dynamic monitoring of live endothelial
      cells. BACKGROUND: PES is widely used in clinics to inhibit restenosis
      effectively. However, late stent thrombosis is a major concern with the use of
      PES. METHODS: We established an in vitro cell culture system to mimic the close
      contact of endothelial cells with PES struts. The dynamic response of porcine
      innominate artery endothelial cells (PIECs) to stents was observed using a bright
      field microscope and a high-resolution charge-coupled device RESULTS: PES changed
      elongated PIECs to round PIECs within 24 hours. Paracellular gaps were readily
      observed in a PIEC monolayer exposed to PES. By contrast, paracellular gaps were
      almost undetectable in an endothelial monolayer incubated with bare metal stent
      (BMS). As incubation time was prolonged (days 5-9), round PIECs returned to their
      elongated shape, but paracellular gaps were retained at lower frequencies and
      smaller sizes than those on days 1 and 2. In addition, the PIEC monolayer in the
      PES group retained an uneven surface topology during incubation, whereas PIECs in
      the BMS group developed a smooth surface of epithelial cell sheets on days 5-7.
      CONCLUSION: Our findings showed that the shift of cell shape causes impaired
      integrity of the monolayer characteristic with enlarged paracellular gaps and
      uneven surface topology in exposure to PES. The results might serve as structural
      information for understanding the mechanism of PES-induced early and late
      thrombosis.

PMID- 24433434
TI  - Model-based clinical pharmacology profiling of ipilimumab in patients with
      advanced melanoma.
AB  - AIM: Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T
      lymphocyte antigen-4. The objective of the present study was to characterize the
      clinical pharmacology profile of ipilimumab using a population pharmacokinetic
      (PPK) approach. METHODS: The PPK model was developed using 2095 ipilimumab serum
      concentration values from 499 patients with unresectable stage III or IV melanoma
      from four phase II studies, with ipilimumab doses ranging from 0.3 to 10 mg kg(
      1) . The structural PK model was determined by developing a base PPK model. The
      effect of covariates on model parameters was assessed by a full covariate model,
      which incorporated all pre-specified covariate-parameter relationships into the
      base model. The final model was developed by backward elimination, followed by
      exclusion of covariates determined not to be of clinical relevance to ipilimumab,
      and was rigorously validated against both internal and external datasets.
      RESULTS: Ipilimumab PK was linear and time-invariant, with dose-proportional
      exposures over the available dose range, yielding a terminal half-life of
      approximately 15 days. Clearance of ipilimumab increased with increasing body
      weight and baseline serum lactate dehydrogenase concentrations, but was not
      affected by age, gender, concomitant budesonide, Eastern Cooperative Oncology
      Group performance status or prior systemic anticancer therapy. Furthermore,
      ipilimumab exposure was not affected by moderate renal impairment or mild hepatic
      impairment. CONCLUSIONS: Ipilimumab concentration-time data were well described
      by a linear, two compartment, zero order i.v. infusion model. The model confirms
      that a body weight-normalized dosing regimen is appropriate for ipilimumab
      therapy in patients with advanced melanoma.

PMID- 24433435
TI  - Groin injecting among a community-recruited sample of people who inject drugs in
      Thailand.
AB  - BACKGROUND: Use of the femoral vein for the injection of illicit drugs (i.e.
      groin injecting) has been linked to various health-related harms, including deep
      vein thrombosis. However, little is known about the prevalence of groin injecting
      and factors that predict this practice among people who inject drugs (PWID) in
      Thailand. We sought to investigate the prevalence and factors associated with
      groin injecting in Bangkok, Thailand. METHODS: Data were derived from the
      Mitsampan Community Research Project in Bangkok between July and October 2011.
      Multivariate logistic regression was used to identify factors associated with
      groin injecting in the last six months. RESULTS: Among 437 participants, 34.3%
      reported groin injecting in the last six months. In multivariate analyses,
      factors positively associated with groin injecting included: having higher than
      secondary education (adjusted odds ratio [AOR] = 1.59; 95% confidence interval
      [CI]: 1.00 - 2.56), weekly midazolam injection (AOR = 8.26; 95% CI: 5.04 -
      14.06), and reports of having had drugs planted on oneself by police (AOR = 2.14;
      95% CI: 1.37 - 3.36). CONCLUSIONS: Over one-third of our sample of Thai PWID
      reported recent groin injecting. Frequent midazolam injection and higher
      education were found to be associated with groin injecting. That high intensity
      PWID were more likely to inject in the groin is concerning given the known
      negative consequences associated with the groin as a site of injection.
      Additionally, PWID who reported drug planting by police were more likely to
      inject in the groin, suggesting that reliance on law enforcement approaches may
      undermine safe injection practices in this setting. These findings highlight the
      need for evidence-based interventions to address the harms associated with groin
      injecting, including efforts to alert PWID to risks of groin injecting, the
      distribution of appropriate injecting equipment, and efforts to encourage use of
      other injecting sites.

PMID- 24433436
TI  - Conserved sex chromosomes across adaptively radiated Anolis lizards.
AB  - Vertebrates possess diverse sex-determining systems, which differ in evolutionary
      stability among particular groups. It has been suggested that poikilotherms
      possess more frequent turnovers of sex chromosomes than homoiotherms, whose
      effective thermoregulation can prevent the emergence of the sex reversals induced
      by environmental temperature. Squamate reptiles used to be regarded as a group
      with an extensive variability in sex determination; however, we document how the
      rather old radiation of lizards from the genus Anolis, known for exceptional
      ecomorphological variability, was connected with stability in sex chromosomes. We
      found that 18 tested species, representing most of the phylogenetic diversity of
      the genus, share the gene content of their X chromosomes. Furthermore, we
      discovered homologous sex chromosomes in species of two genera (Sceloporus and
      Petrosaurus) from the family Phrynosomatidae, serving here as an outgroup to
      Anolis. We can conclude that the origin of sex chromosomes within iguanas largely
      predates the Anolis radiation and that the sex chromosomes of iguanas remained
      conserved for a significant part of their evolutionary history. Next to therian
      mammals and birds, Anolis lizards therefore represent another adaptively radiated
      amniote clade with conserved sex chromosomes. We argue that the evolutionary
      stability of sex-determining systems may reflect an advanced stage of
      differentiation of sex chromosomes rather than thermoregulation strategy.

PMID- 24433437
TI  - Conductive and transparent multilayer films for low-temperature TiO2/Ag/SiO2
      electrodes by E-beam evaporation with IAD.
AB  - Conductive and transparent multilayer thin films consisting of three alternating
      layers (TiO2/Ag/SiO2, TAS) have been fabricated for applications as transparent
      conducting oxides. Metal oxide and metal layers were prepared by electron-beam
      evaporation with ion-assisted deposition, and the optical and electrical
      properties of the resulting films as well as their energy bounding
      characteristics and microstructures were carefully investigated. The optical
      properties of the obtained TAS material were compared with those of well-known
      transparent metal oxide glasses such as ZnO/Ag/ZnO, TiO2/Ag/TiO2, ZnO/Cu/ZnO, and
      ZnO/Al/ZnO. The weathering resistance of the TAS film was improved by using a
      protective SiO2 film as the uppermost layer. The transmittance spectra and sheet
      resistance of the material were carefully measured and analyzed as a function of
      the layer thickness. By properly adjusting the thickness of the metal and
      dielectric films, a low sheet resistance of 6.5 ohm/sq and a high average
      transmittance of over 89% in the 400 to 700 nm wavelength regions were achieved.
      We found that the Ag layer played a significant role in determining the optical
      and electrical properties of this film. 

PMID- 24433438
TI  - Adaptability in protein structures: structural dynamics and implications in
      ligand design.
AB  - The basic framework of understanding the mechanisms of protein functions is
      achieved from the knowledge of their structures which can model the molecular
      recognition. Recent advancement in the structural biology has revealed that in
      spite of the availability of the structural data, it is nontrivial to predict the
      mechanism of the molecular recognition which progresses via situation-dependent
      structural adaptation. The mutual selectivity of protein-protein and protein
      ligand interactions often depends on the modulations of conformations empowered
      by their inherent flexibility, which in turn regulates the function. The
      mechanism of a protein's function, which used to be explained by the ideas of
      'lock and key' has evolved today as the concept of 'induced fit' as well as the
      'population shift' models. It is felt that the 'dynamics' is an essential feature
      to take into account for understanding the mechanism of protein's function. The
      design principles of therapeutic molecules suffer from the problems of plasticity
      of the receptors whose binding conformations are accurately not predictable from
      the prior knowledge of a template structure. On the other hand, flexibility of
      the receptors provides the opportunity to improve the binding affinity of a
      ligand by suitable substitution that will maximize the binding by modulating the
      receptors surface. In this paper, we discuss with example how the protein's
      flexibility is correlated with its functions in various systems, revealing the
      importance of its understanding and for making applications. We also highlight
      the methodological challenges to investigate it computationally and to account
      for the flexible nature of the molecules in drug design. 

PMID- 24433443
TI  - Medicinal Chemistry of New Compounds to Treat Tuberculosis.
AB  - Tuberculosis (TB), a 19th century disease, is still present in the beginning of
      the Third Millennium. It has been considered pandemic, since around two billion
      people are infected with M. tuberculosis. Multi-drug resistant TB has been the
      biggest challenge for chemotherapy. In order to face this severe health problem,
      many institutions, private and public ones, have been investing in the search for
      new and better drug candidates. The pipeline of potential anti-TB drugs presents
      new molecules and formulations that have been submitted to pre-clinical and
      clinical assays. Medicinal Chemistry has an important role towards the objective
      of finding new leads through classic and modern processes. This paper reviews
      some aspects of this search, emphasizing the features of the main compounds under
      investigation and those that are in preliminary and final clinical trials and
      includes the contribution of our laboratory (LAPEN) in the area of designing new
      anti-TB drug candidates.

PMID- 24433439
TI  - Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an
      unfavourable outcome in patients with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The tumour cell microenvironment, which includes local oxygen
      saturation, pericellular pH and stromal cells, can modulate tumour progression.
      This study determined the prognostic impact of infiltrating tumour-associated
      macrophages and the expression of monocarboxylate transporter 4 (MCT4) and
      glypican 3 (GPC3) in hepatocellular carcinoma (HCC) clinical specimens. METHODS:
      A total of 225 cases of resected HCC were subjected to immunohistochemical
      analyses of CD68, CD204, MCT4 and GPC3. Immunoreactivities and other common
      clinicopathological parameters were subjected to univariate prognostic analyses
      for overall survival (OS, n = 225) and disease-free survival (DFS, n = 222). All
      variables with prognostic impact were further analysed in multivariate analysis.
      RESULTS: Increased intratumoural infiltration of CD204-positive or MCT4-positive
      macrophages suggested shorter OS (P = 0.015 or P = 0.001 respectively), but DFS
      was not altered. The GPC3 score (with an emphasis on circumferential
      immunoreactivity) was correlated with shorter OS and DFS. Aberrant expression of
      MCT4 in HCC cells was observed in a subset of HCC cases (21%, 47/225). In those
      cases, significantly poorer OS (P < 0.0001) and DFS (P = 0.0003) were observed,
      and there was a positive correlation with the intratumoural infiltration of CD204
      or MCT4-positive macrophages and the GPC3 score. Multivariate analysis showed
      that aberrant MCT4 expression in HCC cells was an independent prognostic factor
      for shorter OS (P = 0.018) and DFS (P = 0.006) after resection of HCC.
      CONCLUSION: Aberrant expression of MCT4 in carcinoma cells serves as a novel,
      independent prognostic factor for HCC, indicating a poorer patient outcome.

PMID- 24433444
TI  - Vanadium Complexes with Hydrazone or Thiosemicarbazone Ligands as Potential Anti
      Mycobacterium tuberculosis Agents.
AB  - Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium
      tuberculosis (MTB) and still an important public health problem worldwide. Some
      factors like the emergence of multidrug resistant (MDR) and extensively drug
      resistant (XDR) strains make urgent the research of new active compounds.
      Searching for new inorganic compounds against TB, three new dioxovanadium(V)
      complexes were obtained upon reaction of [VO(acac)2] with hydrazone and
      thiosemicarbazone ligands derived from di-2-pyridyl ketone. Spectroscopic studies
      and X-ray crystallography revealed asymmetrically oxo bridged binuclear complexes
      of the type [{VO(L(1,2))}2(MU-O)2], involving the hydrazone ligands, while a
      mononuclear square pyramidal complex of the type [VO2(L(3))] was formed with the
      thiosemicarbazone ligand. The compounds were tested against M. tuberculosis and
      three of them, with MICs values between 2.00 and 3.76 MUM were considered
      promising for TB treatment. Such MIC values are comparable or better than those
      found for some drugs currently used in TB treatment. 

PMID- 24433446
TI  - The purinergic system in allotransplantation.
AB  - The purine nucleotide adenosine triphosphate (ATP) is a universal source of
      energy for any intracellular reaction. Under specific physiological or
      pathological conditions, ATP can be released into extracellular spaces, where it
      binds and activates the purinergic receptors system (i.e. P2X, P2Y and P1
      receptors). Extracellular ATP (eATP) binds to P2X or P2Y receptors in immune
      cells, where it mediates proliferation, chemotaxis, cytokine release, antigen
      presentation and cytotoxicity. eATP is then hydrolyzed by ectonucleotidases into
      adenosine diphosphate (ADP), which activates P2Y receptors. Ectonucleotidases
      also hydrolyze ADP to adenosine monophosphate and adenosine, which binds P1
      receptors. In contrast to P2X and P2Y receptors, P1 receptors exert mainly an
      inhibitory effect on the immune response. In transplantation, a prominent role
      has been demonstrated for the eATP/P2X7R axis; the targeting of this pathway in
      fact is associated with long-term graft function and reduced graft versus host
      disease severity in murine models. Novel P2X receptor inhibitors are available
      for clinical use and are under assessment as immunomodulatory agents. In this
      review, we will focus on the relevance of the purinergic system and on the
      potential benefits of targeting this system in allograft rejection and tolerance.

PMID- 24433447
TI  - Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms
      in systemic lupus erythematosus.
AB  - INTRODUCTION: A C-to-T single nucleotide polymorphism (SNP) located at position
      1858 of human protein tyrosine phosphatase, non-receptor type 22 (PTPN22)
      complementary DNA (cDNA) is associated with an increased risk of systemic lupus
      erythematosus (SLE). How the overall activity of PTPN22 is regulated and how the
      expression of PTPN22 differs between healthy individuals and patients with lupus
      are poorly understood. Our objectives were to identify novel alternatively
      spliced forms of PTPN22 and to examine the expression of PTPN22 isoforms in
      healthy donors and patients with lupus. METHODS: Various human PTPN22 isoforms
      were identified from the GenBank database or amplified directly from human T
      cells. The expression of these isoforms in primary T cells and macrophages was
      examined with real-time polymerase chain reaction. The function of the isoforms
      was determined with luciferase assays. Blood samples were collected from 49
      subjects with SLE and 15 healthy controls. Correlation between the level of
      PTPN22 isoforms in peripheral blood and clinical features of SLE was examined
      with statistical analyses. RESULTS: Human PTPN22 was expressed in several
      isoforms, which differed in their level of expression and subcellular
      localization. All isoforms except one were functionally interchangeable in
      regulating NFAT activity. SLE patients expressed higher levels of PTPN22 than
      healthy individuals and the levels of PTPN22 were negatively correlated with the
      Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology Damage Index (SLICC-DI). CONCLUSIONS: The overall activity of PTPN22
      is determined by the functional balance among all isoforms. The levels of PTPN22
      isoforms in peripheral blood could represent a useful biomarker of SLE.

PMID- 24433448
TI  - Serum bromide concentrations following loading dose in epileptic dogs.
AB  - OBJECTIVE: To determine serum bromide concentrations following an oral loading
      dose in dogs. METHODS: Retrospective review of clinical records of dogs suffering
      from seizures that were treated with bromide. A loading dose of 600 mg/kg
      potassium bromide was administered orally in 17 to 48 hours together with a
      maintenance dose of 30 mg/kg/day. Blood samples were collected within 24 hours
      after completing the protocol and serum bromide concentrations were determined by
      ultra-violet gold chloride colorimetric assay. RESULTS: Thirty-eight dogs were
      included in the study. The median age was 3 (range, 0 . 2 to 10) years and
      bodyweight 21 . 8 (3 . 45 to 46 . 2) kg. The median serum bromide concentration
      was 1 . 26 (0 . 74 to 3 . 6) mg/mL. Thirty-two dogs (84 . 2%) had serum bromide
      concentrations within the therapeutic interval (1 to 3 mg/mL). The serum
      concentration in five dogs (13 . 2%) was just under the minimal therapeutic value
      and in one dog (2 . 6%) it exceeded the maximal therapeutic value (3 . 6 mg/mL).
      CLINICAL RELEVANCE: Following this oral loading dose protocol, serum bromide
      concentrations reach the therapeutic range in the majority of dogs. This
      indicates that the suggested protocol is effective in achieving therapeutic
      concentrations rapidly in epileptic dogs.

PMID- 24433449
TI  - Population pharmacokinetics of levodopa in subjects with advanced Parkinson's
      disease: levodopa-carbidopa intestinal gel infusion vs. oral tablets.
AB  - AIMS: Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa
      carbidopa delivery through intrajejunal infusion. This study characterized the
      population pharmacokinetics of levodopa following a 16 h jejunal infusion of LCIG
      or frequent oral administration of levodopa-carbidopa tablets (LC-oral) in
      subjects with advanced Parkinson's disease (PD). METHODS: A non-linear mixed
      effects model of levodopa pharmacokinetics was developed using serial plasma
      concentrations from an LCIG phase 1 study and a phase 3 double-blind, double
      dummy study of the efficacy and safety of LCIG compared with LC-oral in advanced
      PD patients (n = 68 for model development; 45 on LCIG and 23 on LC-oral). The
      final model was internally evaluated using stochastic simulations and bootstrap
      and externally evaluated using sparse pharmacokinetic data from 311 subjects
      treated in a long term safety study of LCIG. RESULTS: The final model was a two
      compartment model with a transit compartment for absorption, first order
      elimination, bioavailability for LCIG (97%; confidence interval = 95% to 98%)
      relative to LC-oral, different first order transit absorption rate constants
      (LCIG = 9.2 h(-1) vs. LC-oral = 2.4 h(-1) ; corresponding mean absorption time of
      7 min for LCIG vs. 25 min for LC-oral) and different residual (intra-subject)
      variability for LCIG (15% proportional error, 0.3 MUg ml(-1) additive error) vs.
      LC-oral (29% proportional error, 0.59 MUg ml(-1) additive error). Estimated oral
      clearance and steady-state volume of distribution for levodopa were 24.8 l h(-1)
      and 131 l, respectively. CONCLUSIONS: LCIG administration results in faster
      absorption, comparable levodopa bioavailability and significantly reduced intra
      subject variability in levodopa concentrations relative to LC-oral
      administration.

PMID- 24433450
TI  - Successful treatment for graft-versus-host disease after pancreas
      transplantation.
AB  - Graft-versus-host disease (GVHD) after pancreas transplantation is a rare but
      serious complication: All previously reported cases were fatal. We herein report
      three cases of GVHD after pancreas transplantation with favorable outcomes.
      Patients with a history of kidney (and pancreas) transplantation subsequently
      received a pancreas (and kidney) transplantation (i.e., pancreas
      retransplantation or pancreas after kidney transplantation) and developed acute
      GVHD. All of them responded to increased immunosuppression (e.g., steroid bolus,
      antithymocyte globulin) and retained normal graft function. Because the clinical
      manifestations are non-specific, vigilance is necessary to make an accurate
      diagnosis. We underscored the importance of a biopsy of involved organs and the
      clinicopathologic correlation in the early diagnosis of GVHD. Augmented
      immunosuppression to prevent progression from a self-limited disease to life
      threatening pancytopenia or sepsis may be most critical to improve outcome. 

PMID- 24433451
TI  - Interventions to reduce clinical inertia in cardiac risk factor management in
      renal transplant recipients.
AB  - Cardiovascular disease (CVD) is the leading cause of death in renal transplant
      recipients (RTRs). Clinical inertia (CI) is defined as "recognition of the
      problem, but failure to act." The effect of educational interventions in
      minimizing CI in CVD risk factor management was assessed. Educational sessions
      were conducted among 201 RTRs to inform them about their goals for blood pressure
      (BP), low-density lipoprotein cholesterol (LDL-C) and glycated hemoglobin
      (HbA1c). Physicians were reminded about treatment goals using checklists. Pre
      intervention and post-intervention CI was measured as "no action" or "appropriate
      action" by the physicians. Post-intervention percentage of RTRs with "no clinical
      action" for BP, LDL-C, and HbA1c control decreased from 10.8% to 3.8% (P=.02),
      28.2% to 11.1% (P=.008), and 10.3% to 4.5% (P=.05), respectively, while those
      with "appropriate action" increased from 66.2% to 83.3% (P<.001), 68.7% to 79.4%
      (P=.008), and 85.1% to 93.2% (P=.03), respectively. Educational interventions and
      patient participation were shown to reduce CI.

PMID- 24433452
TI  - Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias.
AB  - The BRAF V600E mutation in exon 15 is considered the disease-defining mutation in
      hairy cell leukaemia (HCL), but single HCL cases lacking this mutation have been
      described. In 24 HCL, as well as in 194 various mature B- and T-cell neoplasms,
      we extended the search for BRAF mutations to exon 11. Two V600E-negative HCL
      contained novel, potentially functionally relevant mutations in exon 11 (F468C
      and D449E), while one other HCL was BRAF wild-type in exons 2-17. All non-HCL
      lymphomas lacked BRAF mutations. We therefore suggest screening of BRAF V600E
      negative HCL for alternative exon 11 mutations in the diagnostic setting. 

PMID- 24433453
TI  - Adult phenotype and further phenotypic variability in SRD5A3-CDG.
AB  - BACKGROUND: SRD5A3 is responsible for SRD5A3-CDG, a type of congenital disorder
      of glycosylation, and mutations have been reported in 15 children. All the
      mutations are recessive and truncating. CASE PRESENTATION: We present 2 brothers
      at the age of 38 and 40 years with an initial diagnosis of cerebellar ataxia. We
      found the candidate disease loci via linkage analysis using data from single
      nucleotide polymorphism genome scans and homozygous truncating mutation SRD5A3
      p.W19X, which was previously reported in 3 unrelated children, by exome
      sequencing.Clinical investigations included physical and ocular examinations and
      blood tests. Severe ocular involvement with retinal bone spicule pigmentation and
      optic atrophy are the most prominent disabling clinical features of the disease.
      The serum transferrin isoelectric focusing (TIEF) pattern is abnormal in the
      patient investigated. CONCLUSION: Our patients are older, with later onset and
      milder clinical phenotypes than all patients with SRD5A3-CDG reported so far.
      They also have atypical ocular findings and variable phenotypes. Our findings
      widen the spectrum of phenotypes resulting from SRD5A3 mutations and the clinical
      variability of SRD5A3-CDG, and suggest screening for SRD5A3 mutations in new
      patients with at least a few of the clinical symptoms of SRD5A3-CDG.

PMID- 24433454
TI  - Statistical models to predict type 2 diabetes remission after bariatric surgery.
AB  - BACKGROUND: Type 2 diabetes (T2D) remission may be achieved after bariatric
      surgery (BS), but rates vary according to patients' baseline characteristics. The
      present study evaluates the relevance of several preoperative factors and
      develops statistical models to predict T2D remission 1 year after BS. METHODS: We
      retrospectively studied 141 patients (57.4% women), with a preoperative diagnosis
      of T2D, who underwent BS in a single center (2006-2011). Anthropometric and
      glucose metabolism parameters before surgery and at 1-year follow-up were
      recorded. Remission of T2D was defined according to consensus criteria: HbA1c
      <6%, fasting glucose (FG) <100 mg/dL, absence of pharmacologic treatment. The
      influence of several preoperative factors was explored and different statistical
      models to predict T2D remission were elaborated using logistic regression
      analysis. RESULTS: Three preoperative characteristics considered individually
      were identified as the most powerful predictors of T2D remission: C-peptide (R2 
      = 0.249; odds ratio [OR] 1.652, 95% confidence interval [CI] 1.181-2.309; P =
      0.003), T2D duration (R2  = 0.197; OR 0.869, 95% CI 0.808-0.935; P < 0.001), and
      previous insulin therapy (R2  = 0.165; OR 4.670, 95% CI 2.257-9.665; P < 0.001).
      High C-peptide levels, a shorter duration of T2D, and the absence of insulin
      therapy favored remission. Different multivariate logistic regression models were
      designed. When considering sex, T2D duration, and insulin treatment, remission
      was correctly predicted in 72.4% of cases. The model that included age, FG and C
      peptide levels resulted in 83.7% correct classifications. When sex, FG, C
      peptide, insulin treatment, and percentage weight loss were considered, correct
      classification of T2D remission was achieved in 95.9% of cases. CONCLUSION:
      Preoperative characteristics determine T2D remission rates after BS to different
      extents. The use of statistical models may help clinicians reliably predict T2D
      remission rates after BS.

PMID- 24433455
TI  - Hung jury: testimonies of genital surgery by transsexual men.

PMID- 24433456
TI  - Esophageal baseline impedance levels in patients with pathophysiological
      characteristics of functional heartburn.
AB  - BACKGROUND: Recently, it has been suggested that low esophageal basal impedance
      may reflect impaired mucosal integrity and increased acid sensitivity. We aimed
      to compare baseline impedance levels in patients with heartburn and
      pathophysiological characteristics related to functional heartburn (FH) divided
      into two groups on the basis of symptom relief after proton pump inhibitors
      (PPIs). METHODS: Patients with heartburn and negative endoscopy were treated with
      esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off
      therapy) analysis, patients with normal acid exposure time (AET), normal reflux
      number, and lack of association between symptoms and refluxes were selected; of
      whom 30 patients with a symptom relief higher than 50% after PPIs composed Group
      A, and 30 patients, matched for sex and age, without symptom relief composed
      Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient
      and HV, we evaluated the baseline impedance levels at channel 3, during the
      overnight rest, at three different times. KEY RESULTS: Group A (vs Group B)
      showed an increase in the following parameters: mean AET (1.4 +/- 0.8% vs 0.5 +/-
      0.6%), mean reflux number (30.4 +/- 8.7 vs 24 +/- 6.9), proximal reflux number
      (11.1 +/- 5.2 vs 8.2 +/- 3.6), acid reflux number (17.9 +/- 6.1 vs 10.7 +/- 6.9).
      Baseline impedance levels were lower in Group A than in Group B and in HVs (p <
      0.001). CONCLUSIONS & INFERENCES: Evaluating baseline impedance levels in
      patients with heartburn and normal AET could achieve a better understanding of
      pathophysiology in reflux disease patients, and could improve the distinction
      between FH and hypersensitive esophagus.

PMID- 24433457
TI  - Selection for mechanical advantage underlies multiple cranial optima in new world
      leaf-nosed bats.
AB  - Selection for divergent performance optima has been proposed as a central
      mechanism underlying adaptive radiation. Uncovering multiple optima requires
      identifying forms associated with different adaptive zones and linking those
      forms to performance. However, testing and modeling the performance of complex
      morphologies like the cranium is challenging. We introduce a three-dimensional
      finite-element (FE) model of the cranium that can be morphed into different
      shapes by varying simple parameters to investigate the relationship between two
      engineering-based measures of performance, mechanical advantage and von Mises
      stress, and four divergent adaptive zones occupied by New World Leaf-nosed bats.
      To investigate these relationships, we tested the fit of Brownian motion and
      Ornstein-Uhlenbeck models of evolution in mechanical advantage and von Mises
      stress using dated multilocus phylogenies. The analyses revealed three
      performance optima for mechanical advantage among species from three adaptive
      zones: bats that eat nectar; generalized insectivores, omnivores and some
      frugivores; and bats that specialize on hard canopy fruits. Only two optima, one
      corresponding to nectar feeding, were consistently uncovered for von Mises
      stress. These results suggest that mechanical advantage played a larger role than
      von Mises stress in the radiation of New World Leaf-nosed bats into divergent
      adaptive zones. 

PMID- 24433459
TI  - Verticillium transcription activator of adhesion Vta2 suppresses microsclerotia
      formation and is required for systemic infection of plant roots.
AB  - Six transcription regulatory genes of the Verticillium plant pathogen, which
      reprogrammed nonadherent budding yeasts for adhesion, were isolated by a genetic
      screen to identify control elements for early plant infection. Verticillium
      transcription activator of adhesion Vta2 is highly conserved in filamentous fungi
      but not present in yeasts. The Magnaporthe grisea ortholog conidiation regulator
      Con7 controls the formation of appressoria which are absent in Verticillium
      species. Vta2 was analyzed by using genetics, cell biology, transcriptomics,
      secretome proteomics and plant pathogenicity assays. Nuclear Vta2 activates the
      expression of the adhesin-encoding yeast flocculin genes FLO1 and FLO11. Vta2 is
      required for fungal growth of Verticillium where it is a positive regulator of
      conidiation. Vta2 is mandatory for accurate timing and suppression of
      microsclerotia as resting structures. Vta2 controls expression of 270
      transcripts, including 10 putative genes for adhesins and 57 for secreted
      proteins. Vta2 controls the level of 125 secreted proteins, including putative
      adhesins or effector molecules and a secreted catalase-peroxidase. Vta2 is a
      major regulator of fungal pathogenesis, and controls host-plant root infection
      and H2 O2 detoxification. Verticillium impaired in Vta2 is unable to colonize
      plants and induce disease symptoms. Vta2 represents an interesting target for
      controlling the growth and development of these vascular pathogens. 

PMID- 24433458
TI  - Interaction between stress and the BDNF Val66Met polymorphism in depression: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Major depression is a disabling psychiatric illness with complex
      origins. Life stress (childhood adversity and recent stressful events) is a
      robust risk factor for depression. The relationship between life stress and
      Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has
      received much attention. The aim of the present work was to review and conduct a
      meta-analysis on the results from published studies examining this interaction.
      METHODS: A literature search was conducted using PsychINFO and PubMed databases
      until 22 November 2013. A total of 22 studies with a pooled total of 14,233
      participants met the inclusion criteria, the results of which were combined and a
      meta-analysis performed using the Liptak-Stouffer z-score method. RESULTS: The
      results suggest that the Met allele of BDNF Val66Met significantly moderates the
      relationship between life stress and depression (P = 0.03). When the studies were
      stratified by type of environmental stressor, the evidence was stronger for an
      interaction with stressful life events (P = 0.01) and weaker for interaction of
      BDNF Val66Met with childhood adversity (P = 0.051). CONCLUSIONS: The interaction
      between BDNF and life stress in depression is stronger for stressful life events
      rather than childhood adversity. Methodological limitations of existing studies
      include poor measurement of life stress.

PMID- 24433460
TI  - Fecal microbiota transplantation for refractory Clostridium difficile colitis in
      solid organ transplant recipients.
AB  - Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious
      in individuals with refractory Clostridium difficile. It has not been widely
      studied in individuals with immunosuppression due to concerns about infectious
      complications. We describe two solid organ transplant recipients, one lung and
      one renal, in this case report that both had resolution of their diarrhea caused
      by C. difficile after FMT. Both recipients required two FMTs to achieve
      resolution of their symptoms and neither had infectious complications.
      Immunosuppressed individuals are at high risk for acquisition of C. difficile and
      close monitoring for infectious complications after FMT is necessary, but should
      not preclude its use in patients with refractory disease due to C. difficile.
      Sequential FMT may be used to achieve cure in these patients with damaged
      microbiota from antibiotic use and immunosuppression. 

PMID- 24433461
TI  - Village doctor-assisted case management of rural patients with schizophrenia:
      protocol for a cluster randomized control trial.
AB  - BACKGROUND: Strict compliance with prescribed medication is the key to reducing
      relapses in schizophrenia. As villagers in China lack regular access to
      psychiatrists to supervise compliance, we propose to train village 'doctors'
      (i.e., villagers with basic medical training and currently operating in villages
      across China delivering basic clinical and preventive care) to manage rural
      patients with schizophrenia with respect to compliance and monitoring symptoms.
      We hypothesize that with the necessary training and proper oversight, village
      doctors can significantly improve drug compliance of villagers with
      schizophrenia. METHODS/DESIGN: We will conduct a cluster randomized controlled
      trial in 40 villages in Liuyang, Hunan Province, China, home to approximately 400
      patients with schizophrenia. Half of the villages will be randomized into the
      treatment group (village doctor, or VD model) wherein village doctors who have
      received training in a schizophrenia case management protocol will manage case
      records, supervise drug taking, educate patients and families on schizophrenia
      and its treatment, and monitor patients for signs of relapse in order to arrange
      prompt referral. The other 20 villages will be assigned to the control group
      (case as usual, or CAU model) wherein patients will be visited by psychiatrists
      every two months and receive free antipsychotic medications under an on-going
      government program, Project 686. These control patients will receive no other
      management or follow up from health workers. A baseline survey will be conducted
      before the intervention to gather data on patient's socio-economic status, drug
      compliance history, and clinical and health outcome measures. Data will be re
      collected 6 and 12 months into the intervention. A difference-in-difference
      regression model will be used to detect the program effect on drug compliance and
      other outcome measures. A cost-effectiveness analysis will also be conducted to
      compare the value of the VD model to that of the CAU group.
      DISCUSSION/IMPLICATIONS: Lack of specialists is a common problem in resource
      scarce areas in China and other developing countries. The results of this
      experiment will provide high level evidence on the role of health workers with
      relatively limited medical training in managing severe psychiatric disease and
      other chronic conditions in developing countries. TRIAL REGISTRATION: ChiCTR-TRC
      13003263.

PMID- 24433462
TI  - Dynamic changes in cell-surface expression of mannose in the oral epithelium
      during the development of graft-versus-host disease of the oral mucosa in rats.
AB  - BACKGROUND: The role of cell-surface glycoconjugates in oral mucosal graft-versus
      host disease (GVHD) is still unclear, even though molecular changes in the oral
      epithelium are essential for the pathogenesis of these lesions. In this study, we
      investigated changes in the binding of mannose (Man)-specific Lens culinaris
      lectin (LCA) in the oral mucosa of rats with GVHD. METHODS: Lewis rat spleen
      cells were injected into (Lewis x Brown Norway) F1 rats to induce systemic GVHD,
      including oral mucosal lesions. Tongue and spleen samples were evaluated using
      lectin histochemistry, immunohistochemistry, Western blotting, transwell
      migration assays and Stamper-Woodruff binding assays. RESULTS: Binding of Man
      specific LCA expanded to the epithelial layers of the tongue in GVHD-rats. An
      expansion of LCA binding was related to the increased expression of
      mannosyltransferase in the oral mucosa. CD8+ cells, effector cells of oral
      mucosal GVHD, expressed mannose-binding protein (MBP) and migrated to the medium
      containing Man in the transwell migration assay. Adherence of CD8+ cells to the
      oral epithelium could be inhibited by pretreating CD8+ cells with MBP antibody
      and/or by pretreating sections with Man-specific LCA. CONCLUSIONS: Increased
      expression of Man on keratinocytes leads to the migration and/or adhesion of CD8+
      cells in the surface epithelium, which is mediated in part by the MBP/Man-binding
      pathway during the development of oral mucosal GVHD.

PMID- 24433463
TI  - Review of pharmacological therapies in fibromyalgia syndrome.
AB  - This review addresses the current status of drug therapy for the management of
      fibromyalgia syndrome (FMS) and is based on interdisciplinary FMS management
      guidelines, meta-analyses of drug trial data, and observational studies. In the
      absence of a single gold-standard medication, patients are treated with a variety
      of drugs from different categories, often with limited evidence. Drug therapy is
      not mandatory for the management of FMS. Pregabalin, duloxetine, milnacipran, and
      amitriptyline are the current first-line prescribed agents but have had a mostly
      modest effect. With only a minority of patients expected to experience
      substantial benefit, most will discontinue therapy because of either a lack of
      efficacy or tolerability problems. Many drug treatments have undergone limited
      study and have had negative results. It is unlikely that these failed pilot
      trials will undergo future study. However, medications, though imperfect, will
      continue to be a component of treatment strategy for these patients. Both the
      potential for medication therapy to relieve symptoms and the potential to cause
      harm should be carefully considered in their administration. 

PMID- 24433465
TI  - Haematopoietic stem cell transplantation for severe sickle cell disease in
      childhood: a single centre experience of 50 patients.
AB  - Despite improvements in medical management, sickle cell disease (SCD) remains
      associated with severe morbidity and decreased survival. Allogeneic
      haematopoietic stem cell transplantation (HSCT) remains the only curative
      approach. We report the outcome of 50 consecutive children with severe SCD that
      received HSCT in our unit between November 1988 and April 2013. The stem cell
      source was bone marrow (n = 39), cord blood (n = 3), bone marrow and cord blood
      (n = 7) and peripheral blood stem cells (n = 1). All patients had >=1 severe
      manifestation: 37 presented with recurrent vaso-occlusive crises/acute chest
      syndrome, 27 cerebral vasculopathy and 1 nephropathy. The conditioning regimen
      consisted of busulfan + cyclophosphamide (BuCy) before November 1991 and BuCy +
      rabbit antithymocyte globulin after that date. Since 1995, all patients have been
      treated with hydroxycarbamide (HC) prior to transplantation for a median duration
      of 2.7 years. Median age at transplantation and median follow-up was 8.3 and 7.7
      years, respectively. Acute graft-versus-host disease (GVHD) and chronic GVHD were
      observed in 11 and 10 patients, respectively. An excellent outcome was achieved,
      with 8-year overall survival and event-free survival (EFS) rates of 94.1% and
      85.6%, respectively. Since HC introduction, no graft failure occurred and EFS
      reached 97.4%. Prior treatment with HC may have contributed to successful
      engraftment.

PMID- 24433464
TI  - Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A,
      ABCB1, POR and NR1I2 genotypes on donepezil clearance.
AB  - AIMS: A large interindividual variability in plasma concentrations has been
      reported in patients treated with donepezil, the most frequently prescribed
      antidementia drug. We aimed to evaluate clinical and genetic factors influencing
      donepezil disposition in a patient population recruited from a naturalistic
      setting. METHODS: A population pharmacokinetic study was performed including data
      from 129 older patients treated with donepezil. The patients were genotyped for
      common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron
      transferring protein POR and the nuclear factor NR1I2 involved in CYP activity
      and expression, and in the drug transporter ABCB1. RESULTS: The average donepezil
      clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly
      influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were
      identified as unique significant genetic covariate for donepezil clearance (P <
      0.01), with poor metabolizers and ultrarapid metabolizers demonstrating,
      respectively, a 32% slower and a 67% faster donepezil elimination compared with
      extensive metabolizers. CONCLUSION: The pharmacokinetic parameters of donepezil
      were well described by the developed population model. Functional alleles of
      CYP2D6 significantly contributed to the variability in donepezil disposition in
      the patient population and should be further investigated in the context of
      individual dose optimization to improve clinical outcome and tolerability of the
      treatment.

PMID- 24433466
TI  - Utility of an immune cell function assay to differentiate rejection from
      infectious enteritis in pediatric intestinal transplant recipients.
AB  - The Cylex Immune Cell Function Assay measures cell-mediated immunity based on ATP
      production by stimulated CD4 + cells. We hypothesized that this test would
      discriminate acute cellular rejection (ACR) from infectious enteritis (IE) in
      pediatric intestinal transplant (ITx) recipients with allograft dysfunction. We
      retrospectively analyzed 224 Cylex assays drawn in 47 children who received 53
      ITx. Samples were classified as stable, ACR, or IE based on clinical status. ATP
      values were analyzed using Kruskal-Wallis and t-tests. Overall, there was a
      statistically significant difference in ATP values based on clinical status (p =
      0.03); however, overlap was observed between groups. The median ATP value during
      ACR was significantly greater than during stable periods (p = 0.02). No
      difference was seen in IE vs. stability (p = 0.8). The difference in median ATP
      value in ACR vs. IE approached significance (p = 0.1). Relative to previous
      levels, ACR episodes were associated with a median ATP increase of 101 ng/mL and
      IE episodes with a decrease of 3 ng/mL (p = 0.3). These data indicate that the
      Cylex assay has limited utility in differentiating ACR from IE, largely due to
      interpatient variability. Following longitudinal intrapatient trends may be an
      adjunctive tool in discriminating IE from ACR and guiding immunosuppression
      adjustments in select patients.

PMID- 24433467
TI  - Acute pain medicine: show me the data.

PMID- 24433468
TI  - Analgesic efficacy and mode of action of a selective small molecule angiotensin
      II type 2 receptor antagonist in a rat model of prostate cancer-induced bone
      pain.
AB  - OBJECTIVE: The pathobiology of prostate cancer (PCa)-induced bone pain (PCIBP)
      has both inflammatory and neuropathic components. Previously, we showed that
      small molecule angiotensin II type 2 receptor (AT2 R) antagonists with >1,000
      fold selectivity over the angiotensin II type 1 receptor produced dose-dependent
      analgesia in a rat model of neuropathic pain. Here, we assessed the analgesic
      efficacy and mode of action of the AT2 R antagonist, EMA200, in a rat model of
      PCIBP. METHODS: At 14-21 days after unilateral intratibial injection of AT3B PCa
      cells, rats exhibiting hindpaw hypersensitivity received single intravenous bolus
      doses of EMA200 (0.3-10 mg/kg) or vehicle, and analgesic efficacy was assessed.
      The mode of action was investigated using immunohistochemical, Western blot,
      and/or molecular biological methods in lumbar dorsal root ganglia (DRGs) removed
      from drug-naive and EMA200-treated PCIBP rats relative to sham-control rats.
      RESULTS: Intravenous bolus doses of EMA200 produced dose-dependent analgesia in
      PCIBP rats. Lumbar DRG levels of angiotensin II, nerve growth factor (NGF),
      tyrosine kinase A (TrkA), phospho-p38 mitogen-activated protein kinase (MAPK),
      and phospho-p44/p42 MAPK, but not the AT2 R, were increased significantly (P <
      0.05) in PCIBP rats, c.f. the corresponding levels for sham controls. EMA200
      produced analgesia in PCIBP rats by reducing elevated angiotensin II levels in
      the lumbar DRGs to attenuate augmented angiotensin II/AT2 R signaling. This in
      turn reduced augmented NGF/TrkA signaling in the lumbar DRGs. The net result was
      inhibition of p38 MAPK and p44/p42 MAPK activation. CONCLUSION: Small molecule
      AT2 R antagonists are worthy of further investigation as novel analgesics for
      relief of intractable PCIBP and other pain types where hyperalgesia worsens
      symptoms.

PMID- 24433470
TI  - Ibrutinib: a new frontier in the treatment of chronic lymphocytic leukemia by
      Bruton's tyrosine kinase inhibition.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation
      of nonfunctional mature B cells in blood, bone marrow and lymphoid tissues. In
      the last decade, our understanding of CLL and consequently our diagnostic and
      therapeutic approaches have changed dramatically. Conventional fludarabine based
      chemotherapy has led to improved disease response and longer survival in young
      patients with CLL. However its application in elderly patients has been
      restricted by substantial myelosuppression and infection. Treatment of CLL is now
      moving towards targeted therapy. The success of new class of agents such as
      monoclonal antibodies, proteasome inhibitors and immunomodulatory derivatives has
      sparked further search for treatment agents with novel targets to inhibit. The B
      cell receptor activating pathway involving the Bruton's tyrosine kinase (BTK) is
      crucial in B cell production and maintenance and is an attractive therapeutic
      target. Ibrutinib is an oral covalent inhibitor of the BTK pathway that induces
      apoptosis of B cells. Early phase studies with Ibrutinib either as a single agent
      or in combination regimens have shown promising results with an excellent safety
      profile in patients with high-risk, refractory or relapsed CLL and elderly
      treatment-naive patients. This review summarizes the current knowledge of
      Ibrutinib in the treatment of CLL. 

PMID- 24433472
TI  - Viruses as groundwater tracers: using ecohydrology to characterize short travel
      times in aquifers.
AB  - Viruses are attractive tracers of short (<3 year) travel times in aquifers
      because they have unique genetic signatures, are detectable in trace quantities,
      and are mobile in groundwater. Virus "snaphots" result from infection and
      disappearance in a population over time; therefore, the virus snapshot shed in
      the fecal wastes of an infected population at a specific point in time can serve
      as a marker for tracking virus and groundwater movement. The virus tracing
      approach and an example application are described to illustrate their ability to
      characterize travel times in high-groundwater velocity settings, and provide
      insight unavailable from standard hydrogeologic approaches. Although
      characterization of preferential flowpaths does not usually characterize the
      majority of other travel times occurring in the groundwater system (e.g., center
      of plume mass; tail of the breakthrough curve), virus approaches can trace very
      short times of transport, and thus can fill an important gap in our current
      hydrogeology toolbox. 

PMID- 24433471
TI  - Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic
      nephropathy: a systematic review and meta-analysis.
AB  - BACKGROUND: Nitric oxide (NO) has numerous functions in the kidney, including
      control of renal and glomerular hemodynamics, by interfering at multiple
      pathological and physiologically critical steps of nephron function. Endothelial
      NOS (eNOS) gene has been considered a potential candidate gene to diabetic
      nephropathy (DN) susceptibility. Endothelial nitric oxide synthase gene (eNOS-3)
      polymorphisms have been associated with DN, however some studies do not confirm
      this association. The analyzed polymorphisms were 4b/4a, T-786C, and G986T.
      METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis
      (PRISMA) statement was used in this report. Case-control studies that had
      diabetic patients with DN as cases and diabetic patients without nephropathy as
      controls, as well as that evaluated at least one of the three polymorphisms of
      interest were considered eligible. All studies published up until December 31st,
      2012 were identified by searching electronic databases. Hardy-Weinberg
      equilibrium assessment was performed. Gene-disease association was measured using
      odds ratio estimation based on the following genetic contrast/models: (1) allele
      contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co
      dominant model. RESULTS: Twenty-two studies were eligible for meta-analysis
      (4b/a: 15 studies, T-786C: 5 studies, and G984T: 12 studies). Considering 4b/a
      polymorphism, an association with DN was observed for all genetic models: allele
      contrast (OR = 1.14, CI: 1.04-1.25); additive (OR = 1.77, CI: 1.37-2.28);
      recessive (OR = 1.77, CI: 1.38-2,27); dominant (OR = 1.12, CI: 1.01-1.24), with
      the exception for co-dominance model. As well, T-786C polymorphism showed
      association with all models, with exception for co-dominance model: allele
      contrast (OR = 1.22, CI: 1.07-1.39), additive (OR = 1.52, CI: 1.18-1.97),
      recessive (OR = 1.50, CI: 1.16-1.93), and dominant (OR = 1.11, CI: 1.01-1.23).
      For the G894T polymorphism, an association with DN was observed in allelic
      contrast (OR = 1.12, CI: 1.03-1.25) and co-dominance models (OR = 1.13, CI: 1.04
      1.37). CONCLUSIONS: In the present study, there was association of DN with eNOS
      4b/a and T-786C polymorphism, which held in all genetic models tested, except for
      co-dominance model. G894T polymorphism was associated with DN only in allele
      contrast and in co-dominance model. This data suggested that the eNOS gene could
      play a role in the development of DN.

PMID- 24433473
TI  - Autophagy for tolerance induction in transplantation.

PMID- 24433475
TI  - Progress in European neurology 2012-2013.

PMID- 24433474
TI  - Educational level, prevalence of hysterectomy, and age at amenorrhoea: a cross
      sectional analysis of 9536 women from six population-based cohort studies in
      Germany.
AB  - BACKGROUND: Hysterectomy prevalence has been shown to vary by education level.
      Hysterectomy influences age at amenorrhoea. The aim of this study was to examine
      these associations in Germany within population-based data sets. METHODS:
      Baseline assessments in six population-based cohorts took place from 1997 through
      2006 and included 9,548 women aged 20-84 years. All studies assessed hysterectomy
      history, school and professional degrees. Degrees were categorized into three
      levels each. Adjusted prevalence ratios and 95% confidence intervals (95% CI)
      were estimated. RESULTS: Prevalences were higher in West Germany than East
      Germany, increased by age, and leveled off starting at 55-64 years. The age- and
      study-adjusted prevalence ratio (lowest versus highest school level) was 2.61
      (95% CI: 1.28-5.30), 1.48 (95% CI: 1.21-1.81), and 1.01 (95% CI: 0.80-1.28) for
      women aged 20-45, 45-64, and 65 and more years respectively. The estimated
      adjusted prevalence ratios per one unit decrement of the educational
      qualification score (range 1 = lowest, 8 = highest) were 1.29 (95% CI: 1.02
      1.64), 1.08 (95% CI: 1.04-1.12), and 0.98 (95% CI: 0.93-1.03) for women aged 20
      44, 45-64, and 65-84 years respectively. Age at amenorrhoea was on average 6.2
      years lower (43.5 years versus 49.7 years) among women with a history of
      hysterectomy than those without. CONCLUSIONS: Lower educational level was
      associated with a higher hysterectomy prevalence among women aged 20-64 years.
      Several mediators associated with educational level and hysterectomy including
      women's disease risk, women's treatment preference, and women's access to uterus
      preserving treatment may explain this association. At population level,
      hysterectomy decreases the age of amenorrhoea on average by 6.2 years.

PMID- 24433476
TI  - Bilateral optic neuritis associated with scrub typhus.

PMID- 24433477
TI  - Intramuscular IFNbeta-1a in multiple sclerosis: 'no proof of effectiveness' or
      'proof of no effectiveness'?

PMID- 24433479
TI  - Variations in CCR5, but not HFE, ELMO1, or SLC12A3, are associated with
      susceptibility to kidney disease in north Indian individuals with type 2
      diabetes.
AB  - BACKGROUND: Diabetic nephropathy (DN), the leading cause of end-stage renal
      disease worldwide, may have a genetic component. In the present study, we
      investigated variations in a set of genes with susceptibility to DN in a north
      Indian population. METHODS: Four genes (HFE, ELMO1, SLC12A3, and CCR5) were
      selected on the basis of reported association with type 2 diabetes and
      nephropathy. In all, 417 diabetic subjects (215 without kidney disease [DM] and
      202 with DN) and 197 healthy controls (HC) were evaluated for variations in HFE
      (845 G>A and 187G>C), SLC12A3 (g.34372G>A), CCR5 (59029A>G), and ELMO1 (+9170
      G>A). Polymorphism analysis was performed by polymerase chain reaction
      restriction fragment length polymorphism and Taqman allele discrimination assays.
      RESULTS: Significant differences were found in genotype and allelic frequency in
      SLC12A3 (g.34372G>A) between diabetic subjects and HC (P < 0.03). There were no
      differences in the SLC12A3 g.34372G>A (AA+GA) genotype between diabetic subjects
      with and without nephropathy. However, the CCR5 59029AA genotype and A allele
      were significantly more frequent in diabetics compared with the HC (P = 0.01 and
      0.03, respectively) and subjects with DN versus DM (P = 0.002 and 0.01,
      respectively). For ELMO1 (+9170 G>A), the GG genotype frequency was higher in the
      diabetic versus HC group. There were no differences in the frequency of HFE-845
      G>A and HFE-187G>C among the groups. CONCLUSION: This study shows that the CCR5
      AA genotype is over-represented in subjects with kidney disease due to type 2
      diabetes. The CCR5 59029G>A and ELMO1 (+9170 G>A) loci are more frequent, and the
      SLC12A3 34372 AA genotype is associated with a reduced risk of diabetes.

PMID- 24433480
TI  - Diagnostic accuracy of blood B-cell subset profiling and autoimmunity markers in
      Sjogren's syndrome.
AB  - INTRODUCTION: The aims of this study were to evaluate the diagnostic accuracy of
      blood B-cell subset profiling and immune-system activation marker assays in
      primary Sjogren's syndrome (pSS) and to assess whether adding these tools to the
      current laboratory item would improve the American-European Consensus Group
      (AECG) criteria. METHODS: In a single-center cohort of patients with suspected
      pSS, we tested the diagnostic performance of anti-SSA, antinuclear antibody
      (ANA), rheumatoid factor (RF), gammaglobulins, IgG titers, and B-cell ratio
      defined as (Bm2 + Bm2')/(eBm5 + Bm5), determined using flow cytometry. The
      reference standard was a clinical diagnosis of pSS established by a panel of
      experts. RESULTS: Of 181 patients included in the study, 77 had pSS. By logistic
      regression analysis, only ANA >=1:640 (sensitivity, 70.4%; specificity 83.2%) and
      B-cell ratio >=5 (sensitivity, 52.1%; specificity, 83.2%) showed independent
      associations with pSS of similar strength. In anti-SSA-negative patients,
      presence of either of these two criteria had 71.0% sensitivity but only 67.3%
      specificity for pSS; whereas combining both criteria had 96.2% specificity but
      only 12.9% sensitivity. Adding either of these two criteria to the AECG criteria
      set increased sensitivity from 83.1% to 90.9% but decreased specificity from
      97.1% to 85.6%, whereas adding both criteria in combination did not substantially
      modify the diagnostic performance of the criteria set. The adjunction of RF + ANA
      >=1:320, as proposed in the new American College of Rheumatology (ACR) criteria,
      did not improve the diagnostic value of anti-SSA. CONCLUSIONS: Blood B-cell
      subset profiling is a simple test that has good diagnostic properties for pSS.
      However, adding this test, with or without ANA positivity, does not improve
      current classification criteria.

PMID- 24433481
TI  - Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other
      transporter activities involved in methotrexate clearance.
AB  - AIMS: The urinary coproporphyrin I/(I + III) ratio may be a surrogate for MRP2
      activity. We conducted a prospective study in patients receiving methotrexate
      (MTX) to examine the relationship between this ratio and the pharmacokinetics of
      a MRP2 substrate. METHODS: Three urine samples were collected from 81 patients
      for UCP I/(I + III) ratio determination: one before (P1), one at the end of MTX
      infusion (P2), and one on the day of hospital discharge (P3). Three polymorphisms
      of ABCC2 were analysed and their relationships with basal UCP I/(I + III) ratio
      values assessed. All associated drugs were recorded and a drug interaction score
      (DIS) was assigned. Population pharmacokinetic analysis was conducted to assess
      whether MTX clearance (MTXCL) was associated with the basal UCP I/(I + III)
      ratio, its variation during MTX infusion, the DIS or other common covariates.
      RESULTS: The basal UCP I/(I + III) ratio was not associated with ABCC2
      polymorphisms and did not differ according to the DIS. Significant changes in the
      ratio were observed over time, with an increase between P1 and P2 and a decrease
      at P3 (P < 0.001). No association was found between basal UCP I/(I + III) ratio
      and MTXCL. The final model indicates that MTXCL was dependent on the change in
      the ratio between P1 and P3, DIS and creatinine clearance. CONCLUSION: The basal
      UCP I/(I + III) ratio is not predictive of MTXCL. However, it is sensitive to the
      presence of MTX, so it is plausible that it reflects a function modified in
      response to the drug.

PMID- 24433483
TI  - Coupled cryoconite ecosystem structure-function relationships are revealed by
      comparing bacterial communities in alpine and Arctic glaciers.
AB  - Cryoconite holes are known as foci of microbial diversity and activity on polar
      glacier surfaces, but are virtually unexplored microbial habitats in alpine
      regions. In addition, whether cryoconite community structure reflects ecosystem
      functionality is poorly understood. Terminal restriction fragment length
      polymorphism and Fourier transform infrared metabolite fingerprinting of
      cryoconite from glaciers in Austria, Greenland and Svalbard demonstrated
      cryoconite bacterial communities are closely correlated with cognate metabolite
      fingerprints. The influence of bacterial-associated fatty acids and
      polysaccharides was inferred, underlining the importance of bacterial community
      structure in the properties of cryoconite. Thus, combined application of T-RFLP
      and FT-IR metabolite fingerprinting promises high throughput, and hence, rapid
      assessment of community structure-function relationships. Pyrosequencing revealed
      Proteobacteria were particularly abundant, with Cyanobacteria likely acting as
      ecosystem engineers in both alpine and Arctic cryoconite communities. However,
      despite these generalities, significant differences in bacterial community
      structures, compositions and metabolomes are found between alpine and Arctic
      cryoconite habitats, reflecting the impact of local and regional conditions on
      the challenges of thriving in glacial ecosystems. 

PMID- 24433484
TI  - Do tobacco smoking and illicit drug/alcohol dependence increase the risk of
      mental disorders among men? Evidence from a national urban Bangladeshi sample.
AB  - PURPOSE: This study sought to examine the relationship between tobacco
      consumption or illicit drug/alcohol use and mental disorders. DESIGN AND METHODS:
      We used data from the 2006 Bangladesh Urban Health Survey. The analyses were
      based on the responses of 13,819 men aged 15-59 years. FINDINGS: Smoking of any
      type was associated with an increased risk of mental disorders as were current
      cigarette smoking, heavy cigarette, or bidi smoking status. Ever and current use
      of illicit drugs/alcohol was also associated with a greater risk of mental
      disorders among the participants. PRACTICE IMPLICATIONS: The present findings
      indicate that preventing tobacco smoking and illicit drug/alcohol dependence may
      help reduce the burden caused by mental disorders among urban Bangladeshi men.
      Reducing the risk of common mental health problems may also help reduce the
      prevalence of tobacco consumption and illicit drug/alcohol dependence.

PMID- 24433485
TI  - TET2 gene sequencing may be helpful for myeloproliferative neoplasm diagnosis.

PMID- 24433482
TI  - Neuregulin-1 attenuates mortality associated with experimental cerebral malaria.
AB  - BACKGROUND: Cerebral Malaria (CM) is a diffuse encephalopathy caused by
      Plasmodium falciparum infection. Despite availability of antimalarial drugs, CM
      associated mortality remains high at approximately 30% and a subset of survivors
      develop neurological and cognitive disabilities. While antimalarials are
      effective at clearing Plasmodium parasites they do little to protect against CM
      pathophysiology and parasite-induced brain inflammation that leads to seizures,
      coma and long-term neurological sequelae in CM patients. Thus, there is urgent
      need to explore therapeutics that can reduce or prevent CM pathogenesis and
      associated brain inflammation to improve survival. Neuregulin-1 (NRG-1) is a
      neurotrophic growth factor shown to protect against brain injury associated with
      acute ischemic stroke (AIS) and neurotoxin exposure. However, this drug has not
      been tested against CM-associated brain injury. Since CM-associated brain
      injuries and AIS share similar pathophysiological features, we hypothesized that
      NRG-1 will reduce or prevent neuroinflammation and brain damage as well as
      improve survival in mice with late-stage experimental cerebral malaria (ECM).
      METHODS: We tested the effects of NRG-1 on ECM-associated brain inflammation and
      mortality in P. berghei ANKA (PbA)-infected mice and compared to artemether (ARM)
      treatment; an antimalarial currently used in various combination therapies
      against malaria. RESULTS: Treatment with ARM (25 mg/kg/day) effectively cleared
      parasites and reduced mortality in PbA-infected mice by 82%. Remarkably, NRG-1
      therapy (1.25 ng/kg/day) significantly improved survival against ECM by 73%
      despite increase in parasite burden within NRG-1-treated mice. Additionally, NRG
      1 therapy reduced systemic and brain pro-inflammatory factors TNFalpha, IL-6, IL
      1alpha and CXCL10 and enhanced anti-inflammatory factors, IL-5 and IL-13 while
      decreasing leukocyte accumulation in brain microvessels. CONCLUSIONS: This study
      suggests that NRG-1 attenuates ECM-associated brain inflammation and injuries and
      may represent a novel supportive therapy for the management of CM.

PMID- 24433486
TI  - Photoprotection of human skin beyond ultraviolet radiation.
AB  - Photoprotection of human skin by means of sunscreens or daily skin-care products
      is traditionally centered around the prevention of acute (e.g. sunburn) and
      chronic (e.g. skin cancer and photoaging) skin damage that may result from
      exposure to ultraviolet rays (UVB and UVA). Within the last decade, however, it
      has been appreciated that wavelengths beyond the ultraviolet spectrum, in
      particular visible light and infrared radiation, contribute to skin damage in
      general and photoaging of human skin in particular. As a consequence, attempts
      have been made to develop skin care/sunscreen products that not only protect
      against UVB or UVA radiation but provide photoprotection against visible light
      and infrared radiation as well. In this article, we will briefly review the
      current knowledge about the mechanisms responsible for visible light/infrared
      radiation-induced skin damage and then, based on this information, discuss
      strategies that have been successfully used or may be employed in the future to
      achieve photoprotection of human skin beyond ultraviolet radiation. In this
      regard we will particularly focus on the use of topical antioxidants and the
      challenges that result from the task of showing their efficacy.

PMID- 24433487
TI  - Characteristics, treatment, and health care expenditures of Medicare supplemental
      insured patients with painful diabetic peripheral neuropathy, post-herpetic
      neuralgia, or fibromyalgia.
AB  - OBJECTIVE: To describe the characteristics, treatment, and health care
      expenditures of Medicare Supplemental-insured patients with painful diabetic
      peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), or fibromyalgia.
      DESIGN: Retrospective cohort study. SETTING: United States clinical practice, as
      reflected within a database comprising administrative claims from 2.3 million
      older adults participating in Medicare supplemental insurance programs. SUBJECTS:
      Selected patients were aged >=65 years, continuously enrolled in medical and
      prescription benefits throughout years 2008 and 2009, and had >=1 medical claim
      with an International Classification of Diseases, Ninth Revision, Clinical
      Modification diagnosis code for DPN, PHN, or fibromyalgia, followed within 60
      days by a medication or pain intervention procedure used in treating pDPN, PHN,
      or fibromyalgia during 2008-2009. OUTCOME MEASURES: Utilization of, and
      expenditures on, pain-related and all-cause pharmacotherapy and medical
      interventions in 2009. RESULTS: The study included 25,716 patients with pDPN
      (mean age 75.2 years, 51.2% female), 4,712 patients with PHN (mean age 77.7
      years, 63.9% female), and 25,246 patients with fibromyalgia (mean age 74.4 years,
      73.0% female). Patients typically had numerous comorbidities, and many were
      treated with polypharmacy. Mean annual expenditures on total pain-related health
      care and total all-cause health care, respectively, (in 2010 USD) were: $1,632,
      $24,740 for pDPN; $1,403, $16,579 for PHN; and $1,635, $18,320 for fibromyalgia.
      In age-stratified analyses, pain-related health care expenditures decreased as
      age increased. CONCLUSIONS: The numerous comorbidities, polypharmacy, and
      magnitude of expenditures in this sample of Medicare supplemental-insured
      patients with pDPN, PHN, or fibromyalgia underscore the complexity and importance
      of appropriate management of these chronic pain patients.

PMID- 24433488
TI  - Functional and genetic characterization of clinical malignant hyperthermia
      crises: a multi-centre study.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which
      is characterized by life-threatening metabolic crises during general anesthesia.
      Classical triggering substances are volatile anesthetics and succinylcholine
      (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle
      principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors
      explaining the variable phenotypic presentation and complex pathomechanism, we
      analyzed proven MH events in terms of clinical course, muscle contracture,
      genetic factors and pharmocological triggers. METHODS: In a multi-centre study
      including seven European MH units, patients with a history of a clinical MH
      episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture
      tests (IVCT) were investigated. A test result is considered to be MHE if the
      muscle specimens develop pathological contractures in response to only one of the
      two test substances, halothane or caffeine. Crises were evaluated using a
      clinical grading scale (CGS), results of IVCT and genetic screening. The effects
      of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR)
      were studied in vitro. RESULTS: A total of 200 patients met the inclusion
      criteria. Two MH crises (1%) were triggered by SCh (1 MHS, 1 MHE), 18% by
      volatile anesthetics and 81% by a combination of both. Patients were 70% male and
      50% were younger than 12 years old. Overall, CGS was in accord with IVCT results.
      Crises triggered by enflurane had a significantly higher CGS compared to
      halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1
      variants, of which 14 were novel. CGS varied depending on the location of the
      mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not
      evoke Ca2+ release from isolated rat SR vesicles. CONCLUSIONS: An MH event could
      depend on patient-related risk factors such as male gender, young age and
      causative RyR1 mutations as well as on the use of drugs lowering the threshold of
      myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific
      Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises
      develop in response to the combined administration of SCh and volatile
      anesthetics.

PMID- 24433490
TI  - Elevated production of melatonin in transgenic rice seeds expressing rice
      tryptophan decarboxylase.
AB  - A major goal of plant biotechnology is to improve the nutritional qualities of
      crop plants through metabolic engineering. Melatonin is a well-known bioactive
      molecule with an array of health-promoting properties, including potent
      antioxidant capability. To generate melatonin-rich rice plants, we first
      independently overexpressed three tryptophan decarboxylase isogenes in the rice
      genome. Melatonin levels were altered in the transgenic lines through
      overexpression of TDC1, TDC2, and TDC3; TDC3 transgenic seed (TDC3-1) had
      melatonin concentrations 31-fold higher than those of wild-type seeds. In TDC3
      transgenic seedlings, however, only a doubling of melatonin content occurred over
      wild-type levels. Thus, a seed-specific accumulation of melatonin appears to
      occur in TDC3 transgenic lines. In addition to increased melatonin content, TDC3
      transgenic lines also had enhanced levels of melatonin intermediates including 5
      hydroxytryptophan, tryptamine, serotonin, and N-acetylserotonin. In contrast,
      expression levels of melatonin biosynthetic mRNA did not increase in TDC3
      transgenic lines, indicating that increases in melatonin and its intermediates in
      these lines are attributable exclusively to overexpression of the TDC3 gene. 

PMID- 24433489
TI  - Compliant 3D microenvironment improves beta-cell cluster insulin expression
      through mechanosensing and beta-catenin signaling.
AB  - Type 1 diabetes is chronic disease with numerous complications and currently no
      cure. Tissue engineering strategies have shown promise in providing a therapeutic
      solution, but maintenance of islet function and survival within these therapies
      represents a formidable challenge. The islet microenvironment may hold the key
      for proper islet maintenance. To elucidate the microenvironmental conditions
      necessary for improved islet function and survival, three-dimensional (3D)
      polyacrylamide cell scaffolds were fabricated with stiffnesses of 0.1 and 10 kPa
      to regulate the spatial and mechanical control of biosignals. Specifically, we
      show a significant increase in insulin mRNA expression of 3D primary mouse islet
      derived and Min6-derived beta-cell clusters grown on compliant 0.1 kPa scaffolds.
      Moreover, these compliant 0.1 kPa scaffolds also increase glucose sensitivity in
      Min6-derived beta-cell clusters as demonstrated by the increased glucose
      stimulation index. Our data suggest that stiffness-specific insulin processing is
      regulated through the myosin light chain kinase (MLCK) and Rho-associated protein
      kinase (ROCK) mechanosensing pathways. Additionally, beta-catenin is required for
      regulation of stiffness-dependent insulin expression. Through activation or
      inhibition of beta-catenin signaling, reversible control of insulin expression is
      achieved on the compliant 0.1 kPa and overly stiff 10 kPa substrates.
      Understanding the role of the microenvironment on islet function can enhance the
      therapeutic approaches necessary to treat diabetes for improving insulin
      sensitivity and response. 

PMID- 24433491
TI  - Nine steps to risk-informed wellhead protection and management: a case study.
AB  - Wellhead-protection zones are commonly delineated on the basis of advective
      travel-time analysis without considering any aspects of model uncertainty. In the
      past decade, research efforts have produced quantifiable risk-based safety
      margins for protection zones. These margins are based on well-vulnerability
      criteria (e.g., travel times, exposure times, peak concentrations) and take model
      and parameter uncertainty into account. There are three main reasons why
      practitioners still refrain from applying these new techniques. (1) They fear the
      additional areal demand of probabilistic safety margins; (2) probabilistic
      approaches are allegedly complex, not readily available and require huge
      computing resources, and (3) uncertainty bounds are fuzzy, whereas final
      decisions are binary. The primary goal of this paper is to show that these
      reservations are unjustified. We present a straightforward, computationally
      affordable framework that offers risk-informed decision support for robust and
      transparent wellhead delineation under uncertainty. We show that reliability
      levels can be increased by exchanging delineated low-risk areas for previously
      nondelineated high-risk areas. We also show that further improvements may often
      be available with only little additional delineated area. As proof of our
      concept, we illustrate our key points with the example of a pumped karstic well
      catchment, located in Germany. 

PMID- 24433493
TI  - The effect of nurse-led motivational interviewing on medication adherence in
      patients with bipolar disorder.
AB  - PURPOSE: The purpose of this study was to test the effect of motivational
      interviewing (MI) on medication adherence in patients with bipolar disorder (BD)
      in an outpatient setting. DESIGN AND METHODS: Pretest-posttest design was used.
      The 3-week MI intervention consisted of one face-to-face session and two follow
      up telephone interventions. Outcome measures included medication adherence, self
      efficacy, and motivation to change. FINDINGS: Participants demonstrated
      significant improvement in medication adherence, self-efficacy, and motivation to
      change after receiving the MI. PRACTICE IMPLICATIONS: MI shows promising results
      as a treatment approach to improve medication adherence in adults with BD.
      Psychiatric-mental health nurse practitioners could improve client health
      outcomes by implementing MI techniques.

PMID- 24433492
TI  - The relationship between apelin and cardiac parameters in patients on peritoneal
      dialysis: is there a new cardiac marker?
AB  - BACKGROUND: Many markers have been proposed for CVD risk assessment in dialysis
      population. Apelin is a peptide that has roles in cardiovascular functions and
      volume regulation namely vasodilation, decreased blood pressure (BP), positive
      inotropic effect and inhibition of antidiuretic hormone release. The aim of this
      study was to examine relationship of apelin levels with echocardiographic
      findings and laboratory parameters related with cardiovascular function and bone
      mineral metabolism among peritoneal dialysis (PD) patients. METHODS: This is a
      cross-sectional study in which chronic PD patients aged between 18 and 80 without
      active cardiac, infectious or malignant diseases and hypervolemia have been
      included. Apelin-36 levels and echocardiographic findings were recorded as well
      as clinical and laboratory data. RESULTS: Of the 53 patients, the mean age and
      female/male ratio was 52.8 +/- 15.3 years and 30/23, respectively. Mean apelin
      level was 1.45 +/- 0.37 ng/ml. Gender, drugs (renin-angiotensin-aldosteron
      inhibitors, statins), presence of left ventricular hypertrophy, diabetes
      mellitus, hypertension, hyperlipidemia and significant residual renal function
      did not affect apelin-36 levels. Apelin-36 was correlated negatively with age and
      left atrium diameter; and positively with diastolic BP, ejection fraction (EF),
      total cholesterol, LDL-cholesterol, HDL-cholesterol, parathyroid hormone and
      alkaline phosphatase (ALP) levels. Diastolic BP, LDL-cholesterol, ALP and EF were
      found to be the independent determinants of apelin-36 levels with linear
      regression analysis. CONCLUSIONS: Apelinergic system has important roles in
      volume regulation, cardiovascular functions, lipid metabolism and bone mineral
      disorders in PD patients. Prospective studies with large population are required.

PMID- 24433494
TI  - Asthmatics with exacerbation during acute respiratory illness exhibit unique
      transcriptional signatures within the nasal mucosa.
AB  - BACKGROUND: Acute respiratory illness is the leading cause of asthma
      exacerbations yet the mechanisms underlying this association remain unclear. To
      address the deficiencies in our understanding of the molecular events
      characterizing acute respiratory illness-induced asthma exacerbations, we
      undertook a transcriptional profiling study of the nasal mucosa over the course
      of acute respiratory illness amongst individuals with a history of asthma,
      allergic rhinitis and no underlying respiratory disease. METHODS: Transcriptional
      profiling experiments were performed using the Agilent Whole Human Genome 4X44K
      array platform. Time point-based microarray and principal component analyses were
      conducted to identify and distinguish acute respiratory illness-associated
      transcriptional profiles over the course of our study. Gene enrichment analysis
      was conducted to identify biological processes over-represented within each acute
      respiratory illness-associated profile, and gene expression was subsequently
      confirmed by quantitative polymerase chain reaction. RESULTS: We found that acute
      respiratory illness is characterized by dynamic, time-specific transcriptional
      profiles whose magnitudes of expression are influenced by underlying respiratory
      disease and the mucosal repair signature evoked during acute respiratory illness.
      Most strikingly, we report that people with asthma who experience acute
      respiratory illness-induced exacerbations are characterized by a reduced but
      prolonged inflammatory immune response, inadequate activation of mucosal repair,
      and the expression of a newly described exacerbation-specific transcriptional
      signature. CONCLUSION: Findings from our study represent a significant
      contribution towards clarifying the complex molecular interactions that typify
      acute respiratory illness-induced asthma exacerbations.

PMID- 24433495
TI  - The dystonia discomfort scale (DDS): a novel instrument to monitor the temporal
      profile of botulinum toxin therapy in cervical dystonia.
AB  - BACKGROUND AND PURPOSE: Conventional scales measure the effect of botulinum toxin
      (BT) therapy only at specific points in time. The Dystonia Discomfort Scale
      (DDS), a novel, easy-to-use, self-assessment scale to record temporal profiles of
      the effect of BT therapy in cervical dystonia (CD), is introduced and evaluated
      against the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). METHODS:
      Seventy-six patients with CD (age 54.4 +/- 10.9 years, 34% male) receiving <=5
      cycles of incobotulinumtoxinA (Xeomin); Merz Pharmaceuticals, Frankfurt am Main,
      Germany) injections at intervals >=10 weeks used DDS to record the severity of
      their symptoms daily. DDS data were compared with TWSTRS-Total scores and
      patients' subjective estimation (SE) of the onset (TO) and waning (TW) of the
      treatment effect. RESULTS: The Toronto Western Spasmodic Torticollis Rating Scale
      - Total scores correlated significantly with DDS (P <= 0.028 at all visits
      evaluated). TO-DDS and TO-SE were 7.9 +/- 8.6 and 7.1 +/- 4.1 days, respectively;
      TW-DDS and TW-SE were 41.8 +/- 19.2 and 45.1 +/- 21.5 days, respectively.
      CONCLUSION: The Dystonia Discomfort Scale is a novel, easy-to-use, self
      assessment scale for valid and sensitive monitoring of the temporal profile of
      the effect of BT therapy in patients with CD. DDS provides important additional
      information about onset, duration, waning, stability and reproducibility of the
      effects of BT therapy.

PMID- 24433496
TI  - Is donor glycosylation the gatekeeper for xenotransplantation?

PMID- 24433497
TI  - The M50I polymorphic substitution in association with the R263K mutation in HIV-1
      subtype B integrase increases drug resistance but does not restore viral
      replicative fitness.
AB  - BACKGROUND: First-generation integrase strand-transfer inhibitors (INSTIs), such
      as raltegravir (RAL) and elvitegravir (EVG), have been clinically proven to be
      effective antiretrovirals for the treatment of HIV-positive patients. However,
      their relatively low genetic barrier for resistance makes them susceptible to the
      emergence of drug resistance mutations. In contrast, dolutegravir (DTG) is a
      newer INSTI that appears to have a high genetic barrier to resistance in vivo.
      However, the emergence of the resistance mutation R263K followed by the
      polymorphic substitution M50I has been observed in cell culture. The M50I
      polymorphism is also observed in 10-25% of INSTI-naive patients and has been
      reported in combination with R263K in a patient failing treatment with RAL.
      RESULTS: Using biochemical cell-free strand-transfer assays and resistance assays
      in TZM-bl cells, we demonstrate that the M50I polymorphism in combination with
      R263K increases resistance to DTG in tissue culture and in biochemical assays but
      does not restore the viral fitness cost associated with the R263K mutation.
      CONCLUSIONS: Since the combination of the R263K mutation and the M50I
      polymorphism results in a virus with decreased viral fitness and limited cross
      resistance, the R263K resistance pathway may represent an evolutionary dead-end.
      Although this hypothesis has not yet been proven, it may be more advantageous to
      treat HIV-positive individuals with DTG in first-line than in second or third
      line therapy.

PMID- 24433498
TI  - Relevance of UV filter/sunscreen product photostability to human safety.
AB  - Photostability or photo-instability of sunscreen products is most often discussed
      in undesirable terms with respect to human safety. The health risks, specifically
      associated with sunscreens, photostable or photo-unstable, include
      phototoxic/photoirritation or photoallergic responses and, longer-term, an
      increased risk of skin cancers or photoageing. The aims of this paper are to
      define photostability/photo-instability and objectively assess the acute and
      chronic toxicological consequences from the human exposure to UV
      filter/sunscreens and any probable photo-degradation products. The reported
      prevalence of photoirritation and photoallergic responses to sunscreens is rare
      compared with adverse events, for example, skin irritation or sensitization,
      produced by cosmetics or topically applied drugs and do not directly implicate
      potential photo-degradation products of UV filters. Moreover, for at least one
      photo-unstable combination, octyl methoxycinnamate and avobenzone, the long-term
      benefits to humans, i.e., reduction in skin cancers, seem to outweigh any
      potential adverse consequences attributed to photo-degradation. Sunscreen
      products are formulated to achieve maximum efficacy which, by necessity and
      design, incorporate measures to support and promote photostability since all
      organic UV filters have the potential to photo-degrade. Current performance
      measures, in vivo SPF and in vitro UVA, conducted under standardized conditions,
      in part account for photostability. The concerns expressed when considering human
      exposure to potential photo-unstable UV filters or sunscreen products may not
      manifest as health risks under conditions of use. Still, improvement in sunscreen
      product photostability continues to be a key strategic objective for
      manufacturers.

PMID- 24433499
TI  - Deciding Not to Un-Do the "I Do:" Therapy Experiences of Women Who Consider
      Divorce But Decide to Remain Married.
AB  - This study explores women's experience of marital therapy while they navigated
      decision making around divorce. A qualitative method was used to gain a deeper
      understanding of the participants' therapy and relationship decision-making
      experiences. How are women's decisions whether or not to exit their marriage
      affected by therapy? The researchers interviewed 15 women who had considered
      initiating divorce before they turned 40 and had attended at least five marital
      therapy sessions but ultimately decided not to divorce. In general, participants
      reported that the therapy was helpful to them, their decision-making process and
      their marriages. Five main themes emerged from the interviews: Women Initiated
      Therapy, Therapist Was Experienced as Unbiased, Therapy was Helpful, Importance
      of Extra-therapeutic Factors, and Gradual Process. 

PMID- 24433500
TI  - Luteolin inhibits smooth muscle cell migration and proliferation by attenuating
      the production of Nox4, p-Akt and VEGF in endothelial cells.
AB  - OBJECTIVE: The goals of this study were to observe how luteolin protects
      endothelial cells (ECs) from injury stimulated by Angiotensin II (Ang II),
      investigate the role of vascular endothelial dysfunction in vascular smooth
      muscle cell proliferation and migration in vitro and investigate its primary
      mechanism of action. METHODS: A non-contact coculture system was established
      using a transwell system; ECs were cultured in the lower wells, while the smooth
      muscle cells (SMCs) were cultured in the upper wells. Cell proliferation was
      assessed by the MTT assay. The number of SMCs that migrated through the membrane
      of transwell system were observed and counted. The expression levels of various
      proteins (VEGF, p-Akt, Nox4) expressed in ECs were determined by Western
      blotting. VEGF mRNA expression was detected by reverse transcription-polymerase
      chain reaction (RT-PCR). The supernatants of ECs were measured by enzyme linked
      immunosorbent assay (ELISA) to assay VEGF concentration. RESULTS: Ang II
      stimulated ECs significantly increased the proliferation and migration of SMCs,
      and these effects were inhibited by luteolin pretreatment. Luteolin suppressed
      the Ang II-induced upregulation of Nox4, p-AKT and VEGF expression in ECs.
      CONCLUSION: These results demonstrate that luteolin is capable of inhibiting
      endothelial dysfunction induced by Ang II by suppressing the upregulation of
      Nox4, p-Akt and VEGF, thereby restraining the proliferation and migration of SMCs
      induced by injured ECs.

PMID- 24433502
TI  - Pterostilbene as a potential novel telomerase inhibitor: molecular docking
      studies and its in vitro evaluation.
AB  - Pterostilbene is a naturally occurring dimethyl ether analog of resveratrol
      identified in several plant species. Telomerase is important in tumor initiation
      and cellular immortalization. Given the striking correlations between telomerase
      activity and proliferation capacity in tumor cells, telomerase had been
      considered as a potentially important molecular target in cancer therapeutics.
      Molecular docking studies were performed on pterostilbene with the crystal
      structure of telomerase (3DU6). Pterostilbene was evaluated for its in vitro
      cytotoxicity in breast (MCF7) and lung cancer (NCI H-460) cell lines, antimitotic
      activity in green grams and telomerase activity. Curcumin was used as a standard.
      Docking results indicated good interaction between pterostilbene and the active
      site of telomerase and the docked energy of pterostilbene was -7.10 kcal/mol.
      Pterostilbene showed strong inhibitory effect on in vitro telomerase activity and
      cell growth in both the cell lines tested in a dose dependent manner. Cancer
      cells treated with 80 uM pterostilbene exhibited significant telomerase
      inhibition, after 72 hours (MCF-7 and NCI H-460; 81.52% and 74.69% reduction,
      respectively, compared to control). The IC50 of pterostilbene for anti
      proliferative activity in MCF7 and NCI H-460 cell lines were found to be 30.0 and
      47.2 uM, respectively. The best antimitotic activity was obtained with 80 MUM of
      pterostilbene (100% reduction in water imbibition). All the above results were
      comparable to that of curcumin. The drug-related properties of pterostilbene were
      calculated using Molinspiration, Osiris Property Explorer and ACD/Chemsketch
      softwares. Pterostilbene obeyed Lipinski's Rule of Five indicating its
      therapeutic potential in humans. It was found that the telomerase inhibitory
      activity exhibited by pterostilbene was dependent of the cell viability and has
      the potential to be a new drug candidate against breast and lung cancers. 

PMID- 24433501
TI  - Pharmaceutical applications of graphene-based nanosheets.
AB  - Graphene-based nanosheets (GNS) are atomic-thickness monolayers of hexagonally
      arranged, graphite-derived carbon atoms that may be composed of graphene,
      graphene oxide, or reduced graphene oxide. They have attracted tremendous
      interest for their potential in pharmaceutical applications, due to their unique
      physical, chemical, and mechanical properties GNS exhibit highly uniform surface
      areas and may have hydroxyl (-OH), epoxide (-O-), and carboxyl functional groups
      at their basal surfaces and plane edges, depending on their oxidized and reduced
      surface properties. GNS show high-level optical absorption of near infrared (NIR)
      light and elevate the temperature of nearby environments. Furthermore, they can
      be loaded with anticancer drugs via hydrophobic interactions, pi-pi stacking, or
      electrostatic binding. Given these properties, GNS can be used in chemotherapy,
      photodynamic therapy, photothermal therapy, and theranostics. However, although
      GNS appear to have far-reaching potential in the field of biomedical research,
      their widespread pharmaceutical application has been limited by issues such as
      poor stability in physiological buffers, undefined mechanisms of cellular uptake,
      toxicity problems, and a lack of standard preparation methods. Here, we review
      the current pharmaceutical applications of GNS, focusing on chemotherapy,
      phototherapy, combo therapy and theranostic applications with challenging issues.

PMID- 24433503
TI  - Development and characterization of a gel formulation integrating
      microencapsulated nitrofurazone.
AB  - Nitrofurazone (NTZ) is usually employed in the topical treatment of infected
      wounds and lesions of both skin and mucosa. Microencapsulation is a process
      utilized in the incorporation of active ingredients within polymers aiming at,
      among other objectives, the prolonged release of pharmaceutical compounds and
      protection from atmospheric agents (viz. moisture, light, heat and/or oxidation).
      With the goal of utilizing the microparticles containing encapsulated NTZ in
      pharmaceutical formulations, one prepared microparticles containing NTZ via
      ionotropic gelation of sodium alginate. The microparticles were characterized via
      scanning electron microscopy analyses, Fourier transform infrared spectroscopy
      (FTIR) analyses, via determination of encapsulation efficiency, and via thermal
      analyses (both TGA and DSC). The final gel formulation was also characterized
      rheologically. The extrusion/solidification technique employed to obtain the
      calcium alginate microparticles with encapsulated NTZ was found to be adequate,
      and produced an NTZ encapsulation efficiency of ca. 97.8% +/- 1.1%. The calcium
      alginate microparticles thus obtained, with encapsulated NTZ, exhibited an oval
      shape and hydrodynamic diameters between 500 MUm and 800 MUm. From the thermal
      analyses performed, together with information from the infrared spectra, one may
      conclude that NTZ did not strongly bind to the polymer, which may be favorable
      for the release of the active ingredient. From the results obtained in the
      present research effort, one may conclude that the microparticles produced
      possess the potential to be utilized as carriers for NTZ in pharmaceutical
      formulations such as gels, ointments, and solutions. 

PMID- 24433504
TI  - Construction of an anti-IL-1beta scfv and TNFRI fusion protein and its
      therapeutic effect on RA mice model.
AB  - IL-1beta and TNF-alpha play key roles in the inflammatory response. Their
      abnormal expression may cause the occurrence of various diseases, such as RA.
      Recently, medicines of target TNF-alpha and IL-1beta have become popular in the
      clinical practice. Although these biological agents can get mostly good results,
      they are not effective in all patients. The reason for this result may be that
      these biological agents could not fully inhibit a variety of inflammatory
      cytokines in the inflammatory response. In the present study, a fusion protein
      gene which encoded human interleukin-1beta scfv and soluble TNF receptor I
      (sTNFRI) was cloned. A number of in vitro assays demonstrated that anti-IL-1beta
      scfv/TNFRI simultaneously bound to both targets. The bioactivity assay showed
      that the fusion protein could inhibit both the cytotoxicity of hTNF-alpha on L929
      cells and hIL-1beta-induced proliferation of L929 cells, indicating that the
      fusion protein has the ability to neutralize both hTNF-alpha and hIL-1beta. In
      this study, we established the chicken type II collagen-induced rheumatoid
      arthritis model in Kunming mice, and evaluated the pharmacological effect of the
      fusion protein in vivo. Model mice were randomly divided into 8 groups (n=8): CIA
      model control group, DEX treatment group (1 mg/kg), intraperitoneal treatment
      group (highdose: 5 mg/kg; medium-dose: 2 mg/kg; low-dose: 0.8 mg/kg),
      subcutaneous treatment group (high-dose: 5 mg/kg; medium- dose: 2 mg/kg; low
      dose: 0.8 mg/kg), and healthy mice as control. The control group received the
      same volume of saline. The mice were administrated once every 2 days. Arthritis
      index, anti-CII antibody titers, cytokine levels, histopathological changes were
      examined. The results showed that anti-IL-1beta scfv/TNFRI fusion protein could
      reduce the degree of joint swelling, inflammatory cell infiltration, synovial
      cell proliferation and the level of CII antibody in the sera. The Real-time PCR
      analysis showed that anti-IL-1beta scfv/TNFRI had the ability to reduce the
      expression of IL-1beta, TNF-alpha, IL-17A, MMP-3, IL-6 and improve the expression
      of IL-10 in a dose-dependent manner, suggesting that the fusion protein is the
      mediator for IL-1beta and TNF-alpha involved in the RA process. Compared with DEX
      positive medicine control, anti-IL-1beta scfv/TNFRI appeared more beneficial in
      treatment of CIA mice. The therapeutic effect of the anti-IL-1beta scfv/TNFRI at
      5mg/kg was significantly better than that of DEX treatment. So the anti-IL-1beta
      scfv/TNFRI can become a candidate for treatment of RA. 

PMID- 24433505
TI  - In vivo behavior and safety of lapatinib-incorporated lipid nanoparticles.
AB  - To improve the solubility, bioavailability and anti-tumor effect of lapatinib,
      lapatinib-incorporated lipid nanoparticles (LTNPs) were prepared and
      characterized. The particle size of LTNPs was 88.6 nm with a zeta potential of 20
      mV. Laptinib was loaded into LTNPs with a non-crystal structure as determined by
      FT-IR. In vitro, LTNPs could be effectively uptaken into C6 glioma cells at a
      concentration-dependent manner. In vivo, LTNPs showed a relative higher AUC,
      which was 5.27- and 3.21-fold as that of Tykerb and lapatinib suspension (LTS)
      group. LTNPs also showed highest glioma concentration, which may benefit from the
      enhanced permeability and retention effect and active targeting ability. In
      toxicity studies, LTNPs displayed a half lethal dose over 250 mg/kg. Repeated
      administering 30 mg/kg of LTNPs could led to toxicity to hematology which might
      owe to the bovine serum albumin, a foreign protein to mice. However, there was no
      organic change observed through HE staining. In conclusion, LTNPs could target to
      glioma with high concentration and low side effect. 

PMID- 24433506
TI  - Induction of thyroid neoplasm following plant medicine marine algae (sargassum):
      a rare case and review of the literature.
AB  - In this study induction of neoplasm in thyroid gland of one postoperative patient
      with breast cancer was conducted by marine algae (also seaweed, sargassum), which
      is presented here. A 41-year-old women was diagnosed as her right breast cancer
      complicated with lymph node metastasis in her right axilla on February, 1999. In
      June 19, 1999 she was given the combination chemotherapy of vincristine,
      cyclophosphamide, 5-Fluorouracil and cinobufacini drugs due to two lymph nodes on
      her right superclavicular following radical mastectomy. During chemotherapy she
      was also taken the adjuvant treatment of traditional medicine. Traditional
      medicine consisted of seaweed plant drugs (containing iodine 362,400 ug/kg). As
      to intermittent maintance treatment the total dosage of seaweed herb was at least
      exceeded 500 gram. Induction of thyroid tumor (thumb size) was found in June,
      2001. A thyroidectomy due to thyroma was successfully performed. Histologically
      there revealed thyroid tissue without the evidence of metastasis of breast
      cancer. She had a 5-year survivor. The data indicated oncogenic function of some
      traditional herbs, and further experience of traditional medicine in treating
      thyroid disease especially in thyroid cancer.

PMID- 24433507
TI  - Novel treatment of acute promyelocytic leukemia: As2O3, retinoic acid and
      retinoid pharmacology.
AB  - Acute promyelocytic leukemia(APL), a specific characteristic of t(15;17)
      chromosome translocation, represents 5% to 15% of cases of acute nonlymphocytic
      leukemia. An alternative approach is to consider retinoic acid(all-trans RA, ATRA
      or 13-cis RA or 9-cis RA) plus chemotherapy or RA plus As2O3 regimens as now
      novel therapy. Molecular gene analyses are conclusive in vivo evidence that
      oncogenic PML/RARa plays a crucial role in APL leukemogenesis. As a novel
      approach to APL treatment, one possible the action of RA, A consense sequence (5'
      TCAGGTCATGACCTGA-3') has been postulated for the thyroid hormone (TRE) and
      retinoic acid responsive element (RARE) containing half palindromes, which
      located in the promoter region of target genes. High dose (100-fold) of RA-RARE
      PML/RARa complex in intracellular localization appears to relieve repressor from
      DNA binding, including corepressors N-CoR, SMRT and HDACs, release PML/RARa-
      mediated transcriptional repression, and release histone deacetylase activity
      from PMLRARa. The resulting PML/RARa oncoprotein proteolytic degradation through
      the autophagy-lysosome pathway and the ubiquitin SUMO-proteasome system (UPS), as
      well as caspase 3 (cleavage site Asp522 within a-helics region of PML component
      of the fusion protein) or neutrophil elastase, or lysosomal protease enzyme
      induction. PML protein relocalizes into the wild-type nuclear body (PML-NB)
      configuration or/and wild-type RARa upregulated. An effect to relieve the
      blockade (inhibition) of PML/RARA-mediated RA dependent promyelocytic
      differentiation, and retinoic acid in APL therapy (see Figure in the full text,
      George Zhu, 1991). Here, like v-erbA, PML/RARa is a (strong) transcriptional
      repressor of the RA receptor (RAR) complex, and PML/RARa fusion receptor gene act
      as conditional oncogenic receptor (translocated chimeric retinoic acid a
      signaling) or oncogenic PML/RARa may participate in leukemogenesis of APL through
      blocking RA-mediated promyelocytic differentiation. This is first described in
      eukaryotes.

PMID- 24433508
TI  - Birth prevalence and initial treatment of Robin sequence in Germany: a
      prospective epidemiologic study.
AB  - BACKGROUND: We conducted a monthly epidemiological survey to determine the birth
      prevalence of Robin sequence (RS) and the use of various therapeutic approaches
      for it. METHODS: Between August 2011 and July 2012, every pediatric department in
      Germany was asked to report new admissions of infants with RS to the Surveillance
      Unit for Rare Pediatric Diseases in Germany. RS was defined as retro- or
      micrognathia and at least one of the following: clinically evident upper airway
      obstruction including recessions, snoring or hypoxemia; glossoptosis; feeding
      difficulties; failure to thrive; cleft palate or RS-associated syndrome.
      Hospitals reporting a case were asked to return an anonymized questionnaire and
      discharge letter. RESULTS: Of 96 cases reported, we received detailed information
      on 91. Of these, 82 were included; seven were duplicates and two erroneous
      reports. Given 662,712 live births in Germany in 2011, the birth prevalence was
      12.4 per 100,000 live births. Therapeutic approaches applied included prone
      positioning in 50 infants, followed by functional therapy in 47. Conventional
      feeding plates were used in 34 infants and the preepiglottic baton plate (PEBP)
      in 19. Surgical therapy such as mandibular traction was applied in 2 infants,
      tracheotomy in 3. CONCLUSION: Compared to other cohort studies on RS, surgical
      procedures were relatively rarely used as an initial therapy for RS in Germany.
      This may be due to differences in phenotype or an underrecognition of upper
      airway obstruction in these infants.

PMID- 24433509
TI  - Women's perspectives of female genital cutting: Q-methodology.
AB  - BACKGROUND: Understanding women's perspectives of female genital cutting is
      particularly critical for understanding the roots of the problem and enhancing
      effectiveness of any prevention program. Very limited research has examined how
      people in Iraqi Kurdistan Region think about this practice. This study aimed to
      explore the perspectives of women of female genital cutting with the aim of
      uncovering discrepancies and commonalities between women of different socio
      educational groups. METHODS: An explorative study using Q-methodology was
      conducted with 29 women from different educational and socio-economic statuses in
      Erbil, the main city of the Iraqi Kurdistan Region. Participants were asked to
      rank-order a set of 39 statements about different aspects of female genital
      cutting into a distribution on a scale of nine from "disagree most" to "agree
      most". By-person factor analysis was performed with factors or latent viewpoints
      extracted through centroid method and varimax rotation. RESULTS: A four-factor
      solution and one consensus perspective provided the best conceptual fit for the
      women's perspectives about female genital cutting. Factor 1, entitled "positive
      cultural tradition", centers on recognizing female genital cutting as a positive
      cultural aspect and an essential part of the Kurdish culture. Factor 2, "active
      opponents", positions around actively opposing the practice of female genital
      cutting and considering the practice a violation of human rights. Factor 3, "role
      of law", stresses the importance of developing and enforcing law for combating
      female genital cutting. Factor 4, "health concerns and passive opposition",
      represents the perspectives of recognizing the importance of health concerns
      resulting from female genital cutting and opposition of the practice but not in
      an active manner. A consensus perspective, "marital role", centers primarily on
      lack of effect of female genital cutting on women's marital role. CONCLUSIONS:
      Female genital cutting is still a contentious issue among women in Iraqi
      Kurdistan Region. By identifying disagreement and consensus among women, four
      different perspectives on female genital cutting were uncovered with having
      perspectives at both extremes of accepting the practice and actively opposing it.
      The study highlighted the typical characterizations that are associated with each
      perspective.

PMID- 24433511
TI  - High-pressure headaches, low-pressure syndromes, and CSF leaks: diagnosis and
      management.
AB  - BACKGROUND: Headache resulting from idiopathic intracranial hypertension (IIH) in
      a population of moderately to obese women of childbearing age. The causes overall
      remain unclear. With this review, we provide an overview of clinical treatment
      and management strategies. RESULTS: IIH management is dependent on the signs and
      symptoms presented. Symptomatic treatment should attempt to lower intracranial
      pressure, reduce pain, and protect the optic nerves. Consideration for lumbar
      puncture and draining fluid as an option for reducing pressure may be helpful;
      however, repeated treatment is not usually favored by patients. Traditional
      prophylactic medications used in migraine may help reduce the primary headache
      often induced by raised intracranial pressure. We suggested surgical intervention
      for patients experiencing visual loss or impending visual loss and not responding
      to medication therapy. CONCLUSION: In this review, we discuss headache associated
      with IIH and spontaneous intracranial hypotension. Much needs to be learned about
      treatment options for patients with cerebrospinal fluid leaks including methods
      to strengthen the dura.

PMID- 24433512
TI  - Recurrent facial erythema with burning sensation and increased temperature: a
      variant of erythromelalgia or a new entity?
AB  - OBJECTIVE: Erythromelalgia is a rare clinical syndrome characterized by episodic
      attacks of burning pain, erythema, and increased temperature, primarily affecting
      the extremities, and in rare instances, involving the ear, face, neck, and the
      scrotum. The dermatoscopic features of erythromelalgia in a case with solely
      facial involvement have never been described previously. OBSERVATIONS: We
      describe a 14-year-old female who presented with erythema, burning sensation, and
      warmth on her face only, which mimic the features of erythromelalgia. Physical
      examination showed higher temperature on the involved cheeks than on axillas
      during the episode, while the temperature on both areas was the same between
      episodes. Dermatoscope showed more dilated vessels inside the erythema during the
      episodes than between the episodes. The symptoms had excellent response to the
      combination treatment of gabapentin, indomethacin, and topical lidocaine
      compounds. CONCLUSIONS: The present case is considered to be a variant of
      erythromelalgia. Its erythema may be resulted from the dilated vessels.
      Combination of modalities may provide effective management for erythromelalgia.
      "Erythermalgia" may be better than "erythromelalgia" to describe such conditions.

PMID- 24433513
TI  - Magnetic resonance imaging in adults with epilepsy: a pictorial essay.
AB  - This pictorial essay highlights the role of the radiologist as a member of the
      adult epilepsy multidisciplinary team, and gives an overview of MRI-evident
      epileptogenic lesions. 

PMID- 24433510
TI  - The TRPM4 channel inhibitor 9-phenanthrol.
AB  - The phenanthrene-derivative 9-phenanthrol is a recently identified inhibitor of
      the transient receptor potential melastatin (TRPM) 4 channel, a Ca(2+) -activated
      non-selective cation channel whose mechanism of action remains to be determined.
      Subsequent studies performed on other ion channels confirm the specificity of the
      drug for TRPM4. In addition, 9-phenanthrol modulates a variety of physiological
      processes through TRPM4 current inhibition and thus exerts beneficial effects in
      several pathological conditions. 9-Phenanthrol modulates smooth muscle
      contraction in bladder and cerebral arteries, affects spontaneous activity in
      neurons and in the heart, and reduces lipopolysaccharide-induced cell death.
      Among promising potential applications, 9-phenanthrol exerts cardioprotective
      effects against ischaemia-reperfusion injuries and reduces ischaemic stroke
      injuries. In addition to reviewing the biophysical effects of 9-phenanthrol, here
      we present information about its appropriate use in physiological studies and
      possible clinical applications.

PMID- 24433514
TI  - Potential point of care tests (POCTs) for maternal health in Peru, perspectives
      of pregnant women and their partners.
AB  - BACKGROUND: Globally, no qualitative studies have explored the perspectives of
      women and their partners about the integration of technology - and specifically
      diagnostic testing technologies - into antenatal care. The study objective was to
      describe the demand side for pregnancy-related diagnostic tests from the
      perspective of Peruvian consumers, including female and male community members,
      by engaging participants about their awareness of and care-seeking for pregnancy
      related diagnostic tests and their preferred characteristics and testing
      conditions for pregnancy-related point-of-care diagnostic tests (POCTs). METHODS:
      Sixty-seven mothers and fathers of children under one from the peri-urban coast
      and the peri-urban and rural highlands and jungle of Peru participated in ten
      focus groups. RESULTS: Participants think that pregnancy-related diagnostic tests
      are important and they and their fellow community members are committed to
      ensuring that pregnant women receive the tests they need. Participants expressed
      clear demands for pregnancy-related POCTs, including important characteristics
      for the tests themselves (certification, rapid, reliable results) and for test
      implementation (well-trained, personable good communicators as test
      administrators at well-equipped, convenient testing sites). Participants
      emphasized the importance of short waiting times and explained that many people
      have some ability to pay for POCTs, particularly if they are innovative, rapid or
      multiplex. CONCLUSIONS: Engaging future POCT users as consumers who are able to
      make key decisions about the development and implementation of pregnancy-related
      POCTs is valuable and informative.

PMID- 24433515
TI  - Association of candidate genetic variants with restless legs syndrome in end
      stage renal disease: a multicenter case-control study in Taiwan.
AB  - BACKGROUND AND PURPOSE: Recent genome-wide association studies have shown
      associations between multiple genetic variants and primary restless legs syndrome
      (RLS). Their roles in end stage renal disease (ESRD) related secondary RLS are
      not clear and studies in Asian populations are scarce. The association between
      candidate genetic variants and uremic RLS was investigated in a large cohort of
      Taiwanese dialysis patients. METHODS: Sixteen RLS-related genetic variants at six
      loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the
      intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259
      subjects with and 734 subjects without RLS) were genotyped using TaqMan
      genotyping assays. Multivariate logistic regression analysis was used to test for
      associations between the genotypes and RLS in ESRD. Power calculations were
      completed using the CATs Genetic Power Calculator with settings of a
      multiplicative genetic model. RESULTS: A modest association between the PTPRD
      variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03-2.23, P = 0.03)
      and a trend that TOX3/BC034767 variant rs3104767 may associate with the
      occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95%
      CI 0.97-3.11, P = 0.06). No associations between other genetic variants and risk
      and severity of RLS were observed in our ESRD cohort. CONCLUSIONS: The genetic
      variants of primary RLS candidate genes did not play a major role in our uremic
      RLS populations. The ethnic difference and heterogeneous etiologies underlying
      renal failure may partly explain the minor genetic contribution to uremic RLS in
      our populations. Further studies for other ethnicities will be of worth.

PMID- 24433516
TI  - The prevalence of severe maternal morbidity and near miss and associated factors
      in Sergipe, Northeast Brazil.
AB  - BACKGROUND: The investigation of severe maternal morbidity (SAMM) and maternal
      near miss (NM) and associated risk factors is important for the global reduction
      of maternal mortality. This study investigated the prevalence of SAMM and NM
      cases and the associated risk factors in two reference maternity hospitals in a
      capital city in Northeast-Brazil. METHODS: A cross-sectional study with a nested
      case-control component was conducted from June-2011 to May-2012. Case
      identification was prospective and data collection was performed according to WHO
      criteria and definitions. Odds ratio with confidence intervals and multivariate
      analysis were used whenever possible. RESULTS: There were 16,243 deliveries,
      1,102 SAMM cases, 77 NM cases and 17 maternal deaths. The maternal NM outcome
      ratio was 5.8 cases/1,000 live births (LB); the total prevalence of SAMM + NM was
      72.6 cases/1,000 LB, the maternal near miss: mortality ratio was 4.5cases/1
      maternal death (18% of mortality index). Management-based criteria were the most
      common events for NM (87.1%) and hypertensive disorders for SAMM (67.5%). Higher
      age, previous abortion and caesarean delivery, the non-adhesion to antenatal
      care, current caesarean delivery and bad perinatal results were associated with
      SAMM/NM. In the multivariate analysis, patient's status, previous caesarian and
      abortion and level of consciousness were significant when analyzed together.
      CONCLUSIONS: SAMM and NM situations were prevalent in the studied population and
      some risk factors seem to be associated with the event, particularly previous
      gestational antecedents. Protocols based on SAMM/NM situations can save lives and
      decrease maternal mortality.

PMID- 24433517
TI  - Bone-muscle unit activity, salivary steroid hormones profile, and physical effort
      over a 3-week stage race.
AB  - Muscle traction and bone metabolism are functionally linked and co-regulated by a
      series of factors. Although a role for steroid hormones was hypothesized, a clear
      definition of the bone-muscle interconnection still lacks. To investigate this
      relationship, we studied bone metabolism, muscle activity, and salivary steroid
      hormones profile in relation with the physical effort across a cycling stage
      race, a model of effort in absence of load. Nine pro-cyclists were recruited;
      body weight and power output/energy expenditure were recorded. Diet was kept
      constant. Saliva was collected at days -1, 4, 8, 12, 14, 19, and 23; blood and
      urine were collected at days -1, 12, and 23. Salivary steroid hormones [cortisol,
      dehydroepiandrosterone (DHEA), testosterone, and estradiol], serum lactate
      dehydrogenase (LDH), aspartate aminotransferase (AST) and creatine kinase (CK)
      activities, plasma sclerostin, and urinary calcium and phosphorous were measured.
      Cortisol remained constant, testosterone decreased at day 4, and estradiol and
      DHEA firstly increased and then returned to basal levels. Hormone concentrations
      were not correlated with plasma volume shifts. LDH, CK, AST, sclerostin, and
      urinary calcium and phosphorous increased. DHEA and estradiol correlated with the
      physical effort and the bone-muscular markers. A relationship between muscle
      activity, in absence of load, and bone resorption emerged under a putative
      regulation by DHEA and estradiol. 

PMID- 24433518
TI  - Mindfulness-based relationship education for couples expecting their first child-
      part 1: a randomized mixed-methods program evaluation.
AB  - This article is Part 1 of a two-part series, in which we report on our evaluation
      of a mindfulness-based relationship enhancement program for couples who are
      expecting their first child. In this mixed-methods randomized clinical trial, we
      assigned 33 couples to the 4-week Mindful Transition to Parenthood Program
      treatment group (n = 16 couples) or to a waitlist control condition (n = 17
      couples). Men in the treatment group significantly improved in relationship
      satisfaction, mindfulness, and negative affect; women had no significant
      treatment effects. Small to large effect sizes were present for treatment group
      men and women in multiple areas. Mixed-methods analyses demonstrated that this
      intervention may be especially helpful for men because of differences in social
      support needs, effects of program enrollment, and relational processes in the
      prenatal period.

PMID- 24433521
TI  - Treatment of lysosomal storage diseases: recent patents and future strategies.
AB  - Lysosomal storage diseases (LSDs) are a group of rare genetic multisystemic
      disorders, resulting in deficient lysosomal activity. These pathologies are
      characterized by progressive accumulation of storage material within the
      lysosomes, ultimately leading to organ dysfunctions. LSDs patient's clinical
      outcomes have significantly improved, since the advent of enzyme replacement
      therapy (ERT). ERT is approved worldwide for 6 LSDs: Gaucher disease, Fabry
      disease, Mucopolysaccharidosis types I, II, and VI, and Pompe disease. The
      efficacy and safety of ERT for LSDs has been confirmed by extensive clinical
      trials, however therapy with infused protein is life-long and disease progression
      is still observed in treated patients. Obstacles to successful ERT, such as
      immune reactions against the infused enzyme, miss-targeting of recombinant
      enzymes, and difficult delivery to crucial tissues (i.e. brain and bone),
      determine the need for further research, in order to ameliorate therapeutic
      strategies. Viral gene therapy, stem cell based therapy, pharmacological
      chaperones and could be considered essential tools for future improvement of
      recombinant enzyme trafficking and targeting. This review will discuss recent
      patents and new strategic approaches for enzyme delivery to highlight the most
      relevant aspects, concerning next generation LSDs treatment. 

PMID- 24433519
TI  - Use of myocardial matrix in a chitosan-based full-thickness heart patch.
AB  - A novel cardiac scaffold comprised of decellularized porcine heart matrix was
      investigated for use as a biodegradable patch with a potential for surgical
      reconstruction of the right ventricular outflow tract. Powdered heart matrix
      solution was blended with chitosan and lyophilized to form three-dimensional
      scaffolds. For this investigation, we examined the influence of different
      blending ratios of heart matrix to chitosan on porosity and mechanical
      properties, then gene expression and electrophysiological function of invading
      neonatal rat ventricular myocytes (NRVM) compared to type-A gelatin/chitosan
      composite scaffolds. Heart matrix/chitosan-blended hydrogels (1.6 mg/mL heart
      matrix) had similar porosity (109+/-34 MUm), and elastic modulus (13.2+/-4.0 kPa)
      as previously published gelatin/chitosan scaffolds. Heart matrix/chitosan
      hydrogels maintained>80% viability and had higher NRVM retention (~1000
      cells/mm(2)) than gelatin/chitosan scaffolds. There was a significant increase in
      alpha-myosin heavy chain and connexin-43 expression in NRVM cultured on heart
      matrix/chitosan scaffolds after 14 days compared with gelatin/chitosan scaffolds.
      Further, heart matrix/chitosan scaffolds had significantly higher conduction
      velocity (12.6+/-4.9 cm/s) and contractile stress (0.79+/-0.13 mN/mm(2)) than
      gelatin/chitosan scaffolds. In summary, NRVM cultured on heart matrix scaffold
      showed improvements in contractile and electrophysiological function. 

PMID- 24433522
TI  - Caregivers' acceptance of alternatives to long-term psychiatric hospitalization;
      lessons and debates from the South Korean situation.
AB  - BACKGROUND: A political movement towards building alternatives to long-term
      hospitalization of psychiatric patients in Korea has gained momentum. We aimed to
      provide sturdy foundation needed to formulate the most rational policy by review
      of caregiver's opinion to the political alternatives under discussion for
      facilitating discharge of long-term stayed psychiatric patients in Korea.
      DISCUSSION: Caregivers in Korea, whose family members had been hospitalized
      longer than 6 months and all of whom applied to the Mental Health Review Board
      (MHRB) for an examination required for extended stay, have shown reluctance to
      take their patients back home. Especially, a half of them answered that if MHRB
      would order compulsory discharge, they would take their patients to another
      hospital instead of living together. Despite of those pessimistic attitudes, one
      of the promising solutions might be residential care as an alternative to the
      long-term hospital care, which is most preferred by caregivers. CONCLUSION: After
      all, the issue of who should take an accountability of the psychiatric patients
      is essential in establishing mental health policy. Korean government should
      analyze and reform mental health delivery systems such as residential service
      system, community-based case management programs and hospital treatment systems
      including payment program which can facilitate reasonable decision by
      professionals as well as caregivers for the appropriate admission rather than
      longer term hospitalizations.

PMID- 24433523
TI  - Diagnostic utility of molecular and cytogenetic analysis in lipoblastoma: a study
      of two cases and review of the literature.
AB  - AIMS: Lipoblastoma is a benign neoplasm of embryonic white fat tissue that
      results from the proliferation of primitive adipocytes, in which histological
      features can be ambiguous. In order to discriminate between lipoblastoma and
      other lipogenic and lipomatous tumours, we studied chromosomal alterations and
      protein expression in two cases of lipoblastoma in infants. METHODS AND RESULTS:
      Standard cytogenetic analysis, fluorescence in-situ hybridization, array
      comparative genomic hybridization and Western blotting allowed us to demonstrate
      the presence of chromosome abnormalities involving the 8q11-13 region containing
      the pleomorphic adenoma gene 1 (PLAG1), which are classically reported in
      lipoblastoma, and aberrant expression of PLAG1. CONCLUSIONS: This report
      illustrates two different tumorigenic pathways implicating PLAG1 in lipoblastoma:
      amplification through multiple copies of a small marker chromosome derived from
      chromosome 8, and a paracentric inversion of the long arm of chromosome 8. Both
      these anomalies induced aberrant expression of PLAG1, emphasizing the role of
      PLAG1 in tumorigenesis. The aberrant expression of PLAG1 protein has been
      hypothesized, but this is the first report to demonstrate its occurrence in
      lipoblastoma.

PMID- 24433524
TI  - Patients with anorexia nervosa who self-injure: a phenomenological study.
AB  - PURPOSE: This study investigates self-injury from the perspective of patients
      with anorexia nervosa. DESIGN AND METHODS: A phenomenological design was used.
      Twelve patients participated. Data were collected using a semi-structured
      interview guide. FINDINGS: Participants display self-injurious behavior
      predominantly in situations when they are forced to eat. They are terrified of
      gaining weight and use self-injurious behavior to cope with their anxiety. Self
      injury is envisioned as a technique to regain control of their own eating pattern
      without bothering anyone. They feel shame for not controlling their emotions more
      constructively. PRACTICE IMPLICATIONS: Healthcare professionals should
      systematically observe signals and explore less harmful strategies that help to
      regulate overwhelming feelings.

PMID- 24433525
TI  - Parenteral treatment of episodic tension-type headache: a systematic review.
AB  - BACKGROUND: Tension-type headache is highly prevalent in the general population
      and is a consistent if not frequent cause of visits to acute care settings.
      Analgesics such as nonsteroidal anti-inflammatory drugs, acetaminophen, and
      salicylates are considered first-line therapy for treatment of tension-type
      headache. For patients who present to an acute care setting with persistent
      tension-type headache despite analgesic therapy, it is not clear which parenteral
      agent should be administered. We performed a systematic review of the medical
      literature to determine whether parenteral therapies other than salicylates or
      nonsteroidals are efficacious for acute tension-type headache. METHODS: We
      performed a systematic review of Medline, EMBASE, CINAHL, Google scholar, and the
      Cochrane Central Registry of Controlled Trials from inception through August,
      2012 using the search terms "tension-type headache" and "parenteral or
      subcutaneous or intramuscular or intravenous." Our goal was to identify
      randomized trials in which one parenteral treatment was compared to another
      active comparator or to placebo for the acute relief of tension-type headache.
      Parenteral was defined as intravenous, intramuscular, or subcutaneous
      administration. We only included studies that distinguished tension-type headache
      from other primary headache disorders, such as migraine. The primary outcome for
      this review was measures of efficacy one hour after medication administration.
      Data abstraction was performed by two authors. Disagreements were resolved by a
      third author. We assessed the internal validity of trials using the Cochrane
      Collaboration risk of bias tool. Because of the small number of trials
      identified, and the substantial heterogeneity among study design and medications,
      we decided that combining data and reporting summary statistics would serve no
      useful function. The results of individual studies are presented using Number
      Needed to Treat (NNT) with 95%CI when dichotomous outcomes were available and
      continuous outcomes otherwise. RESULTS: Our search returned 640 results. One
      hundred eighty-seven abstracts were reviewed, and 8 studies involving 486
      patients were included in our analysis. The most common reasons for exclusion of
      abstracts were no assessment of acute pain relief, use of nonparenteral
      medications only, and no differentiation of headache type. Risk of bias ranged
      from low to high. The following medications were more effective than placebo for
      acute pain (NNT, 95%CI): metamizole (4, 2-26), chlorpromazine (4, 2-26), and
      metoclopramide (2, 1-3). The combination of metoclopramide + diphenhydramine was
      superior to ketorolac (4, 2-8) The following medications were not more effective
      than placebo: mepivacaine, meperidine + promethazine, and sumatriptan.
      CONCLUSIONS: Various parenteral medications other than salicylates or
      nonsteroidals provide acute relief of tension-type headache. Comparative efficacy
      studies are needed.

PMID- 24433526
TI  - Correlation between severity of lumbar spinal stenosis and lumbar epidural
      steroid injection.
AB  - OBJECTIVE: Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal that
      causes mechanical compression of the spinal nerve roots. The compression of these
      nerve roots can cause leg pain, as well as neurogenic claudication. Lumbar
      epidural steroid injections have commonly been used in patients with LSS. The aim
      of our study was to determine the relationship between the severity of LSS using
      a grading system (grade 1 = mild stenosis with separation of all cauda equina;
      grade 2 = moderate stenosis with some cauda equina aggregated; grade 3 = severe
      stenosis with none of the cauda equina separated) and the subject's response to
      computed tomography-guided lumbar epidural steroid injection (CTG-LESI) and to
      evaluate the short-term effectiveness. METHODS: Forty-seven consecutive patients
      with degenerative LSS were enrolled in this prospective study. All subjects
      underwent lumbar spine magnetic resonance imaging. Two radiologists independently
      graded lumbar central canal stenosis based on T2-weighted axial images. All CTG
      LESI were performed in the procedure room. Outcome measures were obtained using
      the 5-point patient's satisfaction scale at 2 and 8 weeks post-treatment. To
      evaluate the outcome, we divided the patients into two groups according to their
      response to the treatment. RESULTS: Improvement (including reports of slightly
      improved, much improved, and no pain) was observed in 37 patients (78.7%) at 2
      weeks and 36 patients (77.6%) at 8 weeks after the procedure. There was no
      statistically significant correlation between pain relief and age. CONCLUSIONS:
      The grade of LSS appears to have no effect on the degree of pain relief
      associated with CTG-LESI. However, CTG-LESI seems to provide effective short-term
      pain relief due to LSS.

PMID- 24433527
TI  - Acid-sensing ion channels activation and hypoxia upregulate Homer1a expression.
AB  - BACKGROUND: Recent studies have indicated that dynamic alterations in the
      structure of postsynaptic density (PSD) are involved in the pathogenesis of many
      central nervous system disorders, including ischemic stroke. Homer is the newly
      identified scaffolding protein located at PSD and regulates synaptic function.
      Homer1a, an immediate early gene, has been shown to be induced by several
      stimulations, such as glutamate, brain-derived neurotrophic factor, and trauma.
      However, whether acidosis mediated by acid-sensing ion channels (ASICs) and
      hypoxia during cerebral ischemia can change Homer1a expression remains to be
      determined. RESULTS: We investigated that acidosis and hypoxia selectively and
      rapidly upregulated Homer1a expression, but not Homer1b/c in cultured cortical
      neurons. We also found that Homer1a exhibited induction expression in brain
      cortex of the middle cerebral artery occlusion (MCAO) rats. Additionally, acid
      evoked Homer1a mRNA induction depended on extracellular signal-regulated
      kinase1/2 (ERK1/2) and Akt activity, and ASIC1a-mediated calcium influx whereas
      hypoxia depended only on ERK1/2 activity. Also, we demonstrated that continuous
      acidosis and hypoxia resulted in pronounced cell injury and Homer1a knockdown
      with small interfering RNA aggravated this damage induced by 3 h acid and hypoxia
      incubation in neuro-2a cells. CONCLUSION: Homer1a might act as an activity
      dependent regulator responding to extracellular stimuli during cerebral ischemia.

PMID- 24433528
TI  - The relation between student motivation and student grades in physical education:
      A 3-year investigation.
AB  - Enhancing students' academic engagement is the key element of the educational
      process; hence, research in this area has focused on understanding the mechanisms
      that can lead to increased academic engagement. The present study investigated
      the relation between motivation and grades in physical education (PE) employing a
      3-year longitudinal design. Three hundred fifty-four Greek high school students
      participated in the study. Students completed measures of motivation to
      participate in PE on six occasions; namely, at the start and the end of the
      school year in the first, second, and third year of junior high school. Students'
      PE grades were also recorded at these time points. The results of the multilevel
      growth models indicated that students' PE grades increased over the 3 years and
      students had better PE grades at the end of each year than at the beginning of
      the subsequent year. In general, students and classes with higher levels of
      controlling motivation achieved lower PE grades, whereas higher levels of
      autonomous motivation were associated with higher PE grades. These findings
      provide new insight on the associations between class- and individual-level
      motivation with objectively assessed achievement in PE. 

PMID- 24433529
TI  - Health facility-based data on women receiving sulphadoxine-pyrimethamine during
      pregnancy in Tanzania: lessons to learn from a cross-sectional survey in Mkuranga
      and Mufindi districts and other national survey reports.
AB  - BACKGROUND: A study of health facility (HF) data on women receiving sulphadoxine
      pyrimethamine (SP) for intermittent preventive treatment of malaria during
      pregnancy (IPTp) was carried out at antenatal care clinics in Mkuranga and
      Mufindi districts. METHODS: A review of health management information system
      (HMIS) registers, interviews with health-care workers (HWs) and district and
      national level malaria control program managers corroborated by inter-temporal
      assessment through observations at HF levels. Statistical data were analyzed in
      Excel and interpreted in triangulation with qualitative data from interviews and
      observations. RESULTS: Data indicated that IPTp doses administered to women were
      inadequate and partly inconsistent. HMIS registers lacked space for IPT records,
      forcing HWs to manipulate their record-keeping. The proportion/number of IPTp
      recipients in related to the supply of SP for free delivery, to women's
      attendance behaviours, showed variation by quarter and year of reporting.
      CONCLUSION: It is impossible to achieve rational health service planning when the
      HMIS is weak. Whilst it is acknowledged that the HMIS is already overloaded,
      concerted measures are urgently needed to accommodate data on new interventions
      and other vertical programs if malaria programs are to achieve their goals.

PMID- 24433530
TI  - A qualitative study exploring women's beliefs about physical activity after
      stillbirth.
AB  - BACKGROUND: Research provides strong evidence for improvements in depressive
      symptoms as a result of physical activity participation in many populations
      including pregnant and post-partum women. Little is known about how women who
      have experienced stillbirth (defined as fetal death at 20 or more weeks of
      gestation) feel about physical activity or use physical activity following this
      experience. The purpose of this study was to qualitatively explore women's
      beliefs about physical activity following a stillbirth. METHODS: This was an
      exploratory qualitative research study. Participants were English-speaking women
      between the ages of 19 and 44 years who experienced a stillbirth in the past year
      from their recruitment date. Interviews were conducted over the phone or in
      person based on participants' preferences and location of residence and
      approximately 30-45 minutes in length. RESULTS: Twenty-four women participated in
      the study (M age = 33 +/- 3.68 years; M time since stillbirth = 6.33 +/- 3.06
      months). Women's beliefs about physical activity after stillbirth were coded into
      the following major themes: barriers to physical activity (emotional symptoms and
      lack of motivation, tired, lack of time, guilt, letting go of a pregnant body,
      and seeing other babies), benefits to physical activity (feeling better
      emotionally/mentally, helping women to cope or be therapeutic), importance of
      physical activity (working through grief, time for self), motivators for physical
      activity (body shape/weight, health, more children, be a role model, already an
      exerciser). Health care providers and their role in physical activity
      participation was also a major theme. CONCLUSIONS: This is the first study to
      qualitatively explore beliefs about physical activity in women after a
      stillbirth. Women who have experienced stillbirth have unique beliefs about
      physical activity related to their experience with stillbirth. Findings from this
      study may help to improve the health and quality of life for women who have
      experienced stillbirth by utilizing physical activity as a strategy for improving
      depressive symptoms associated with experiencing a stillbirth. Future research in
      this area is highly warranted.

PMID- 24433531
TI  - Meta-analysis and candidate gene mining of low-phosphorus tolerance in maize.
AB  - Plants with tolerance to low-phosphorus (P) can grow better under low-P
      conditions, and understanding of genetic mechanisms of low-P tolerance can not
      only facilitate identifying relevant genes but also help to develop low-P
      tolerant cultivars. QTL meta-analysis was conducted after a comprehensive review
      of the reports on QTL mapping for low-P tolerance-related traits in maize. Meta
      analysis produced 23 consensus QTL (cQTL), 17 of which located in similar
      chromosome regions to those previously reported to influence root traits.
      Meanwhile, candidate gene mining yielded 215 genes, 22 of which located in the
      cQTL regions. These 22 genes are homologous to 14 functionally characterized
      genes that were found to participate in plant low-P tolerance, including genes
      encoding miR399s, Pi transporters and purple acid phosphatases. Four cQTL loci
      (cQTL2-1, cQTL5-3, cQTL6-2, and cQTL10-2) may play important roles for low-P
      tolerance because each contains more original QTL and has better consistency
      across previous reports. 

PMID- 24433532
TI  - A prospective pilot study to assess neoadjuvant chemotherapy for unresectable
      peritoneal carcinomatosis from colorectal cancer.
AB  - AIM: Twelve to 13% of patients with colorectal cancer (CRC) develop peritoneal
      carcinomatosis (PC), the majority of whom present with unresectable disease. This
      study aimed to document the actual response rate to and response characteristics
      of preoperative modern systemic chemotherapy in this patient group. METHOD:
      Patients underwent a positron emission tomography (PET)/CT scan, laparoscopy and
      peritoneal biopsy to document unresectable PC. After four courses of preoperative
      chemotherapy (capecitabine/oxaliplatin +/- bevacizumab), the extent of PC was re
      evaluated by PET/CT(or CT), laparoscopy and peritoneal biopsy (if considered
      safe). RESULTS: Ten patients (seven men, three women) with good performance
      status of median age 60.3 (45.6-72.8) years were studied. The first laparoscopy
      documented unresectable PC. One patient was excluded because of systemic
      metastases on PET/CT. Nine proceeded to follow the trial protocol. Of these, one
      developed early progressive disease, two had macroscopically stable disease and
      five had progressive disease at second laparoscopy. One patient developed a small
      bowel perforation at first laparoscopy and received palliative chemotherapy
      outside the protocol, after which progressive disease was found at an explorative
      laparotomy. Thus, 7 (78%) patients with unresectable PC from CRC developed
      progressive disease under neoadjuvant chemotherapy and 2 (22%) patients remained
      stable. No clear macroscopic response to chemotherapy could be demonstrated.
      CONCLUSION: Unresectable PC from CRC does not respond well to systemic
      chemotherapy.

PMID- 24433533
TI  - Sexuality and body image following treatment for early-stage vulvar cancer: a
      qualitative study.
AB  - AIM: To describe women's experiences of sexuality and body image following
      treatment for early-stage vulvar cancer. BACKGROUND: There is limited information
      available on sexual function following treatment for early-stage vulvar cancer. A
      review of the literature has shown a lack of qualitative investigation into this
      topic. This study was undertaken to address this deficiency and to add to the
      existing body of knowledge describing the psychosexual outcomes for these women.
      DESIGN: Qualitative interview study. METHODS: A qualitative approach based on
      interpretive phenomenology was used to interview a purposive sample of 10 women
      (mean age 58 years) who had previously been treated for an early-stage vulvar
      cancer. Interviews were conducted from June-October 2009. Data were generated
      from verbatim transcription of the semi-structured in-depth interviews. Thematic
      analysis of these data revealed themes that were common to the women's
      experiences of sexuality and body image. FINDINGS: Four themes were identified
      that described the structure of the experience. Only two of these themes,
      sexuality and body image, will be discussed in this paper. CONCLUSIONS: Findings
      from this study indicated that the majority of women experienced little to no
      long-term disruption to sexuality and body image following conservative treatment
      for early-stage vulvar cancer. Intimacy and relationship status were more closely
      linked to women's sexual satisfaction than physical arousal. Factors contributing
      to women experiencing negative emotions were radical vulvar excision, multiple
      vulvar procedures and/or the development of lymphoedema.

PMID- 24433534
TI  - Genistein inhibits tumor invasion by suppressing multiple signal transduction
      pathways in human hepatocellular carcinoma cells.
AB  - BACKGROUND: Genistein (Gen) exhibits anti-mutagenic and anti-metastatic
      activities in hepatoma cell lines. Gen has suppressive effects on tumor growth
      and angiogenesis in nude mice. Gen suppresses the enzymatic activity of matrix
      metalloproteinase (MMP)-9; however, the mechanism underlying its anti-invasive
      activity on hepatocellular carcinoma (HCC) cells is unclear. METHODS: In this
      study, the possible mechanisms underlying Gen-mediated reduction of 12-O
      Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of
      secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7,
      and HA22T) and murine embryonic liver cells (BNL CL2) were investigated. RESULTS:
      Gen suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and
      nuclear factor-kappa B (NF-kappaB) activity. Gen suppressed TPA-induced AP-1
      activity through inhibitory phosphorylation of extracellular signal-related
      kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and TPA
      stimulated inhibition of NF-kappaB nuclear translocation through IkappaB
      inhibitory signaling pathways. Moreover, Gen suppressed TPA-induced activation of
      ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-kappaB and AP-1.
      CONCLUSIONS: Gen and its inhibition of multiple signal transduction pathways can
      control the invasiveness and metastatic potential of HCC.

PMID- 24433535
TI  - Microbial community structures differentiated in a single-chamber air-cathode
      microbial fuel cell fueled with rice straw hydrolysate.
AB  - BACKGROUND: The microbial fuel cell represents a novel technology to
      simultaneously generate electric power and treat wastewater. Both pure organic
      matter and real wastewater can be used as fuel to generate electric power and the
      substrate type can influence the microbial community structure. In the present
      study, rice straw, an important feedstock source in the world, was used as fuel
      after pretreatment with diluted acid method for a microbial fuel cell to obtain
      electric power. Moreover, the microbial community structures of anodic and
      cathodic biofilm and planktonic culturewere analyzed and compared to reveal the
      effect of niche on microbial community structure. RESULTS: The microbial fuel
      cell produced a maximum power density of 137.6 +/- 15.5 mW/m2 at a COD
      concentration of 400 mg/L, which was further increased to 293.33 +/- 7.89 mW/m2
      through adjusting the electrolyte conductivity from 5.6 mS/cm to 17 mS/cm.
      Microbial community analysis showed reduction of the microbial diversities of the
      anodic biofilm and planktonic culture, whereas diversity of the cathodic biofilm
      was increased. Planktonic microbial communities were clustered closer to the
      anodic microbial communities compared to the cathodic biofilm. The
      differentiation in microbial community structure of the samples was caused by
      minor portion of the genus. The three samples shared the same predominant phylum
      of Proteobacteria. The abundance of exoelectrogenic genus was increased with
      Desulfobulbus as the shared most abundant genus; while the most abundant
      exoelectrogenic genus of Clostridium in the inoculum was reduced. Sulfate
      reducing bacteria accounted for large relative abundance in all the samples,
      whereas the relative abundance varied in different samples. CONCLUSION: The
      results demonstrated that rice straw hydrolysate can be used as fuel for
      microbial fuel cells; microbial community structure differentiated depending on
      niches after microbial fuel cell operation; exoelectrogens were enriched; sulfate
      from rice straw hydrolysate might be responsible for the large relative abundance
      of sulfate reducing bacteria.

PMID- 24433536
TI  - Implementing evidence-informed policy into practice for health care professionals
      managing people with low back pain in Australian rural settings: a preliminary
      prospective single-cohort study.
AB  - OBJECTIVE: To provide access to professional development opportunities for health
      care professionals, especially in rural Australian regions, consistent with
      recommendations in the Australian National Pain Strategy and state government
      policy. DESIGN AND SETTING: A preliminary prospective, single-cohort study
      design, which aligned health policy with evidence-informed clinical practice,
      evaluated the implementation and effectiveness of an interprofessional, health
      care provider pain education program (hPEP) for management of nonspecific low
      back pain (nsLBP) in rural Western Australia. INTERVENTION: The 6.5-hour hPEP
      intervention was delivered to 60 care providers (caseload nsLBP 19.8% +/- 22.5)
      at four rural WA regions. OUTCOME MEASURES: Outcomes were recorded at baseline
      and 2 months post-intervention regarding attitudes, beliefs (modified Health Care
      Providers Pain and Impairment Relationship Scale [HC-PAIRS]), Back Pain Beliefs
      Questionnaire [BBQ]), and self-reported evidence-based clinical practice
      (knowledge and skills regarding nsLBP, rated on a 5-point Likert scale with 1 =
      nil and 5 = excellent). RESULTS: hPEP was feasible to implement. At 2 months post
      hPEP, responders' (response rate 53%) improved evidence-based beliefs were
      indicated by HC-PAIRS scores: baseline mean (SD) [43.2 (9.3)]; mean difference
      (95% CI) [-5.9 (-8.6 to -3.1)]; and BBQ baseline [34.3 (6.8)]; mean difference
      [2.1 (0.5 to 3.6)]. Positive shifts were observed for all measures of clinical
      knowledge and skills (P < 0.001) and increased assistance with planning lifestyle
      changes (P < 0.001), advice on self-management (P = 0.010), and for decreased
      referrals for spinal imaging (P = 0.03). CONCLUSIONS: This policy-into-practice
      educational program is feasible to implement in rural Western Australia (WA).
      While preliminary data are encouraging, a further randomized controlled trial is
      recommended.

PMID- 24433537
TI  - Can citrate efflux from roots improve phosphorus uptake by plants? Testing the
      hypothesis with near-isogenic lines of wheat.
AB  - Phosphorus (P) deficiency in some plant species triggers the release of organic
      anions such as citrate and malate from roots. These anions are widely suggested
      to enhance the availability of phosphate for plant uptake by mobilizing sparingly
      soluble forms in the soil. Carazinho is an old wheat (Triticum aestivum) cultivar
      from Brazil, which secretes citrate constitutively from its root apices, and here
      we show that it also produces relatively more biomass on soils with low P
      availability than two recent Australian cultivars that lack citrate efflux. To
      test whether citrate efflux explains this phenotype, we generated two sets of
      near-isogenic lines that differ in citrate efflux and compared their biomass
      production in different soil types and with different P treatments in glasshouse
      experiments and field trials. Citrate efflux improved relative biomass production
      in two of six glasshouse trials but only at the lowest P treatments where growth
      was most severely limited by P availability. Furthermore, citrate efflux provided
      no consistent advantage for biomass production or yield in multiple field trials.
      Theoretical modeling indicates that the effectiveness of citrate efflux in
      mobilizing soil P is greater as the volume of soil into which it diffuses
      increases. As efflux from these wheat plants is restricted to the root apices,
      the potential for citrate to mobilize sufficient P to increase shoot biomass may
      be limited. We conclude that Carazinho has other attributes that contribute to
      its comparatively good performance in low-P soils. 

PMID- 24433538
TI  - Identification of a novel pathway involving a GATA transcription factor in yeast
      and possibly in plant Zn uptake and homeostasis.
AB  - To gain a better understanding of the regulation of Zn homeostasis in plants and
      the degree of conservation of Zn homeostasis between plants and yeast, a cDNA
      library from the Zn/Cd hyperaccumulating plant species, Noccaea caerulescens, was
      screened for its ability to restore growth under Zn limiting conditions in the
      yeast mutant zap1Delta. ZAP1 is a transcription factor that activates the Zn
      dependent transcription of yeast genes involved in Zn uptake, including ZRT1, the
      yeast high affinity Zn transporter. From this screen two members of the E2F
      family of transcription factors were found to activate ZRT1 expression in a Zn
      independent manner. The activation of ZRT1 by the plant E2F proteins involves E2F
      mediated activation of a yeast GATA transcription factor which in turn activates
      ZRT1 expression. A ZRT1 promoter region necessary for activation by E2F and GATA
      proteins is upstream of two zinc responsive elements previously shown to bind
      ZAP1 in ZRT1. This activation may not involve direct binding of E2F to the ZRT1
      promoter. The expression of E2F genes in yeast does not replace function of ZAP1;
      instead it appears to activate a novel GATA regulatory pathway involved in Zn
      uptake and homeostasis that is not Zn responsive. 

PMID- 24433539
TI  - The prevalence of migraine in restless legs syndrome.
AB  - OBJECTIVE: While previous studies have investigated the prevalence of restless
      legs syndrome (RLS) in patients with migraine, we aimed to explore the prevalence
      and characteristics of migraine in adult patients diagnosed with RLS.
      BACKGROUNDS: The association of primary headaches, especially of migraine, with
      RLS has recently attracted much attention. Migraine prevalence was reported to be
      higher in patients with RLS than in the general population, and the role of
      dopamine was strengthened. METHODS: We evaluated 265 consecutive adult RLS
      patients (137 males and 128 females) followed up in a Sleep Disorders Unit and
      diagnosed according to criteria defined by the International Restless Legs
      Syndrome Study Group (IRLSSG). RLS characteristics, and the severity, were
      performed by using the IRLSSG severity scale. The diagnosis of headache subtypes
      was defined by the International Classification of Headache Disorders. Gender,
      age, age at RLS onset, duration of RLS, family history of RLS, family history of
      headache, presence of depression, any treatments given for RLS, and the change in
      headache following RLS treatment were questioned. RESULTS: The mean age of the
      study population was 50.4 +/- 12.8 years, mean age at RLS onset was 41.6 +/- 13.2
      years, and mean disease duration was 8.40 +/- 8.6 years. Of these, 163 patients
      had headache; 40 of them were diagnosed to have migraine-type headache (15.1%).
      The presence of migraine-type headache was 9.4% in males with RLS, and 21.1% in
      female RLS patients. In RLS patients with migraine, 67.5% were females, while
      48.0% of RLS patients with other types of headache were females (P = .032), and
      only 41.2% of RLS patients without headache were females (P = .005). The severity
      of RLS was significantly higher in patients with migraine compared with those
      without headache (P < .001). The presence of depression, the family history of
      RLS, and headache were also higher in patients with migraine compared with RLS
      patients with other types of headache or those without headache. Thirty-six
      patients with headache reported partial or substantial benefit from RLS
      treatment. CONCLUSIONS: Our results did not suggest higher rates of migraine-type
      headache in RLS patients when compared with population-based prevalence studies
      from Turkey. Alternatively, the severity of RLS was significantly higher in
      patients with migraine. Although the increase in these scores does not constitute
      a relationship etiopathogenetic, it suggests a correlation between the type cross
      model nociceptive systems. Moreover, the family history of RLS was higher in
      patients with migraine. The prevalence of migraine in patients with RLS, however,
      waits to be better demonstrated.

PMID- 24433540
TI  - Physiological cost and thermal envelope: a novel approach to cycle garment
      evaluation during a representative protocol.
AB  - This study aimed to examine thermoregulation in different clothing assemblies
      during a representative cycling exercise protocol. Six men undertook cycling
      exercise simulating representative thermal exchange challenges while wearing low
      (LOW), intermediate (INT1 and INT2), or high (HI) amounts of clothing. Exercise
      was conducted at 14.5  degrees C, 46.8% relative humidity and included a "flat"
      [45 min at 35% peak power output (PPO), wind speed 8.3 m/s], "uphill" (30 min at
      55% PPO, wind speed 3.6 m/s), and "downhill" (20 min at 50 W, wind speed 16.7
      m/s) stage. Rectal temperature changed with the exercise stage and was
      independent of clothing assembly. In contrast, an "envelope" was evident for mean
      body temperature, resulting from differences in mean skin temperature between the
      LOW and HI conditions. The elevated mean body temperature in HI was associated
      with increased physiological "cost," in the form of increased sweat production
      and heart rate. Physiological cost provides a better index of clothing
      performance than deep body temperature in the "thermoregulatory zone," as a
      consequence sports clothing should attempt to optimize the balance between
      comfort and reduced physiological cost.

PMID- 24433541
TI  - STMN-1 is a potential marker of lymph node metastasis in distal esophageal
      adenocarcinomas and silencing its expression can reverse malignant phenotype of
      tumor cells.
AB  - BACKGROUND: Distal esophageal adenocarcinoma is a highly aggressive neoplasm.
      Despite advances in diagnosis and therapy, the prognosis is still poor. Stathmin
      (STMN-1) is a ubiquitously expressed microtubule destabilizing phosphoprotein. It
      promotes the disassembly of microtubules and prevents assembly. STMN-1 can cause
      uncontrolled cell proliferation when mutated and not functioning properly.
      Recently, found to be overexpressed in many types of human cancers. However, its
      clinical significance remains elusive in distal esophageal adenocarcinoma. Here,
      we reported for the first time that STMN-1 is highly overexpressed in
      adenocarcinomas of the distal esophagus and strongly associated with lymph node
      metastasis. METHODS: STMN-1 expression in 63 cases of distal esophageal
      adenocarcinoma was analyzed by immunoblotting, while expression in esophageal
      adenocarcinoma cells was determined by immunocytochemistry, immunofluorescence,
      qRT-PCR and western blotting. Lentivirus-mediated RNAi was employed to knock-down
      STMN-1 expression in Human esophageal adenocarcinoma cells. The relationship
      between STMN-1 expression and lymph node metastasis in distal esophageal
      adenocarcinoma was determined by univariate and multivariate analyses. RESULTS:
      STMN-1 was detected in 31 (49.21%) of the 63 cases. STMN-1 was highly
      overexpressed in specimens with lymph node metastasis pN (+), but its expression
      was almost undetected in pN (-) status. Multivarian regression analysis
      demonstrated that STMN-1 overexpression is an independent factor for lymph node
      metastasis in distal esophageal adenocarcinoma. STMN-1 shRNA effectively reduced
      STMN-1 expression in esophageal adenocarcinoma cells (P < 0.05), which
      significantly suppressed proliferation (P < 0.05), increased migration (P < 0.05)
      and invasion ability (P < 0.05) and G1 phase arrest (P < 0.05) which lead to
      induction of apoptosis in esophageal adenocarcinoma cells in vitro. To verify the
      in vitro data, we conducted in vivo tumor xenograft studies. Esophageal
      adenocarcinoma cells stably transfected with STMN-1 shRNA significantly reduced
      tumor xenografts volume in vivo. CONCLUSIONS: STMN-1 overexpression is associated
      with lymph node metastasis and increase malignancy in distal esophageal
      adenocarcinoma. In vivo and in vitro laboratory findings, suggests that STMN-1
      may be a suitable target for future therapeutic strategies in distal esophageal
      adenocarcinoma.

PMID- 24433542
TI  - The karrikin response system of Arabidopsis.
AB  - Arabidopsis thaliana provides a powerful means to investigate the mode of action
      of karrikins, compounds produced during wildfires that stimulate germination of
      seeds of fire-following taxa. These studies have revealed close parallels between
      karrikin signalling and strigolactone signalling. The two perception systems
      employ similar mechanisms involving closely related alpha/beta-fold hydrolases
      (KAI2 and AtD14) and a common F-box protein (MAX2). However, karrikins and
      strigolactones may be distinguished from each other and elicit different
      responses. The karrikin response requires a newly discovered protein (SMAX1), a
      homologue of rice protein D53 that is required for the strigolactone response.
      Mutants defective in the response to karrikins have seeds with increased
      dormancy, altered seedling photomorphogenesis and modified leaf shape. As the
      karrikin and strigolactone response mechanisms are so similar, it is speculated
      that the endogenous signalling compound for the KAI2 system may be a specific
      strigolactone. However, new results show that the proposed endogenous signalling
      compound is not produced by the known strigolactone biosynthesis pathway via
      carlactone. Structural studies of KAI2 protein and its interaction with karrikins
      and strigolactone analogues provide some insight into possible protein-ligand
      interactions, but are hampered by lack of knowledge of the endogenous ligand. The
      KAI2 system appears to be present throughout angiosperms, implying a
      fundamentally important function in plant biology. 

PMID- 24433544
TI  - A meal or a male: the 'whispers' of black widow males do not trigger a predatory
      response in females.
AB  - INTRODUCTION: Female spiders are fine-tuned to detect and quickly respond to prey
      vibrations, presenting a challenge to courting males who must attract a female's
      attention but not be mistaken for prey. This is likely particularly important at
      the onset of courtship when a male enters a female's web. In web-dwelling
      spiders, little is known about how males solve this conundrum, or about their
      courtship signals. Here we used laser Doppler vibrometry to study the vibrations
      produced by males and prey (house flies and crickets) on tangle webs of the
      western black widow Latrodectus hesperus and on sheet webs of the hobo spider
      Tegenaria agrestis. We recorded the vibrations at the location typically occupied
      by a hunting female spider. We compared the vibrations produced by males and prey
      in terms of their waveform, dominant frequency, frequency bandwidth, amplitude
      and duration. We also played back recorded male and prey vibrations through the
      webs of female L. hesperus to determine the vibratory parameters that trigger a
      predatory response in females. RESULTS: We found overlap in waveform between male
      and prey vibrations in both L. hesperus and T. agrestis. In both species, male
      vibrations were continuous, of long duration (on average 6.35 s for T. agrestis
      and 9.31 s for L. hesperus), and lacked complex temporal patterning such as
      repeated motifs or syllables. Prey vibrations were shorter (1.38 - 2.59 s),
      sporadic and often percussive. Based on the parameters measured, courtship
      signals of male L. hesperus differed more markedly from prey cues than did those
      of T. agrestis. Courtship vibrations of L. hesperus males differed from prey
      vibrations in terms of dominant frequency, amplitude and duration. Vibrations of
      T. agrestis males differed from prey in terms of duration only. During a playback
      experiment, L. hesperus females did not respond aggressively to low-amplitude
      vibrations irrespective of whether the playback recording was from a prey or a
      male. CONCLUSIONS: Unlike courtship signals of other spider species, the
      courtship signals of L. hesperus and T. agrestis males do not have complex
      temporal patterning. The low-amplitude 'whispers' of L. hesperus males at the
      onset of courtship are less likely to trigger a predatory response in females
      than the high-amplitude vibrations of struggling prey.

PMID- 24433543
TI  - Sense codon emancipation for proteome-wide incorporation of noncanonical amino
      acids: rare isoleucine codon AUA as a target for genetic code expansion.
AB  - One of the major challenges in contemporary synthetic biology is to find a route
      to engineer synthetic organisms with altered chemical constitution. In terms of
      core reaction types, nature uses an astonishingly limited repertoire of
      chemistries when compared with the exceptionally rich and diverse methods of
      organic chemistry. In this context, the most promising route to change and expand
      the fundamental chemistry of life is the inclusion of amino acid building blocks
      beyond the canonical 20 (i.e. expanding the genetic code). This strategy would
      allow the transfer of numerous chemical functionalities and reactions from the
      synthetic laboratory into the cellular environment. Due to limitations in terms
      of both efficiency and practical applicability, state-of-the-art nonsense
      suppression- or frameshift suppression-based methods are less suitable for such
      engineering. Consequently, we set out to achieve this goal by sense codon
      emancipation, that is, liberation from its natural decoding function - a
      prerequisite for the reassignment of degenerate sense codons to a new 21st amino
      acid. We have achieved this by redesigning of several features of the post
      transcriptional modification machinery which are directly involved in the
      decoding process. In particular, we report first steps towards the reassignment
      of 5797 AUA isoleucine codons in Escherichia coli using efficient tools for tRNA
      nucleotide modification pathway engineering. 

PMID- 24433545
TI  - A large parosteal ossifying lipoma of lower limb encircling the femur.
AB  - INTRODUCTION: Lipoma is a benign soft tissue neoplasm that may contain
      mesenchymal elements, as a result of metaplastic process. Ossification in benign
      and malignant soft tissue tumors can also manifest due to metaplastic process.
      CASE PRESENTATION: A 45 year old woman presented with a large thigh mass. The
      mass was developed one and a half year ago which insidiously increased in size
      and was associated with movement restriction. Radiological findings revealed soft
      tissue neoplasm on antero-medial aspect of thigh encircling the femur and
      displacing adjacent muscles. Fine trabeculations were seen in neoplasm suggestive
      of ossification. Excision of the mass was performed and histopathology revealed
      adipocytes with mature bony trabeculae possessing prominent osteoblastic rimming
      suggestive of ossifying lipoma. CONCLUSION: It is important to recognize this
      variant of lipoma as it is associated with a better clinical outcome in contrast
      to most of the deep seated soft tissue neoplasms. Secondly it should also be
      differentiated from myositis ossificans and heterologous differentiation in other
      soft tissue neoplasms. We suggest an algorithmic approach to the diagnosis of
      ossifying soft tissue neoplasms histopathologically. Mature bony trabeculae with
      prominent osteoblastic rimming in a soft tissue lesion are due to a metaplastic
      process and should not be confused with osteosarcoma.

PMID- 24433546
TI  - Functional gastrointestinal disorders in patients with familial Mediterranean
      fever.
AB  - AIM: Familial Mediterranean fever (FMF) is an autosomal recessive
      autoinflammatory disease characterised by recurrent episodes of fever and
      polyserositis. To date, insufficient data regarding the prevalence of functional
      gastrointestinal disorders such as irritable bowel syndrome (IBS) and functional
      dyspepsia (FD) have been reported in patients with FMF. This study aimed to
      determine the prevalence of functional gastrointestinal disorders in patients
      with FMF. METHODS: This study included 122 patients with FMF and a control group
      of 122 healthy volunteers who were similar with respect to age and sex. Clinical
      data were collected and gastrointestinal complaints were evaluated according to
      the Rome III criteria. RESULTS: IBS was found in 18% of the patients and 10.7% of
      the controls (P > 0.05). Dyspepsia was reported in 37.7% of the patients and
      35.2% of the controls. Constipation was significantly higher in the control group
      (15.6% vs. 7.4%, P = 0.045), whereas diarrhoea was reported significantly more
      often in patients with FMF (P = 0.001). CONCLUSIONS: IBS and dyspepsia were not
      increased in patients with FMF, whereas diarrhoea was more frequently reported.

PMID- 24433547
TI  - The future of research in craniofacial biology and what this will mean for oral
      health professional education and clinical practice.
AB  - Today, and looking to the future, scientific discoveries from cellular,
      developmental and molecular biology inform our understanding of cell, tissue and
      organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel,
      muscle, nerve and many organs such as salivary glands and teeth. Present day
      biomedical science yields principles for the biomimetic design and fabrication of
      cells, tissues and organs. Bioengineering has become a strategy that can 'mimic'
      biological processes, and inform clinical procedures for tissue and organ
      replacements. The future of regenerative craniofacial biology holds enormous
      promise for the diagnosis and treatment of congenital birth defects, traumatic
      injuries, degenerative chronic diseases as well as for Mendelian single gene and
      complex multigene diseases and disorders. The past 50 years have heralded the
      completion of the human genome and the introduction of 'personalized medicine and
      dentistry', the utilization of stem cell therapy for an array of diseases and
      disorders, the 'proof of principle' to reverse select inherited diseases such as
      anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary
      research drawn from the diverse biomedical sciences. Looking to the future, we
      can readily anticipate as major goals to emphasize the clinician's role in
      identifying clinical phenotypes that can lead to differential diagnosis, and
      rejuvenate missing or damaged tissues by establishing processes for the
      utilization of gene, cell and/or protein therapies. The future is replete with
      remarkable opportunities to enhance clinical outcomes for congenital as well as
      acquired craniofacial malformations. Clinicians play a pivotal role because
      critical thinking and sound clinical acumen substantially improve diagnostic
      precision and thereby clinical health outcomes.

PMID- 24433548
TI  - Advancement in shampoo (a dermal care product): preparation methods, patents and
      commercial utility.
AB  - Shampoo is a cleaning aid for hair and is the most evolving beauty products in
      the present scenario. Today's shampoo products are of great importance as they
      provide cleaning of hair with the benefits of conditioning, smoothing and good
      health of hair i.e. dandruff, dirt, grease and lice free hair. Various types of
      shampoos depending upon function, nature of ingredient, and their special effects
      are elaborated in this study. Generally shampoos are evaluated in terms of
      physical appearance, detergency, surface tension, foam quality, pH, viscosity,
      and percent of solid content, flow property, dirt dispersion, cleaning action,
      stability and wetting time. The attention should be paid at its patent portion
      which attracts towards itself as it provides wide knowledge related to shampoo.
      This article reviews the various aspects of shampoo in terms of preparation
      methods, various patents and commercial value. 

PMID- 24433549
TI  - Prevalence and factors associated with use of herbal medicine among women
      attending an infertility clinic in Uganda.
AB  - BACKGROUND: Infertility is a public health problem associated with devastating
      psychosocial consequences. In countries where infertility care is difficult to
      access, women turn to herbal medicines to achieve parenthood. The aim of this
      study was to determine the prevalence and factors associated with herbal medicine
      use by women attending the infertility clinic. METHODS: This was a cross
      sectional study of 260 women attending the infertility clinic at Mulago hospital.
      The interviewer administered questionnaire comprised socio-demographic
      characteristics, infertility-related aspects and information on herbal medicine
      use. The main outcome measure was herbal medicines use for infertility treatment.
      Determinants of herbal medicine use were assessed using multivariable logistic
      regression. RESULTS: The majority (76.2%) of respondents had used herbal
      medicines for infertility treatment. The mean age of the participants was 28.3
      years +/- 5.5. Over 80% were married, 59.6% had secondary infertility and 2/3 of
      the married participants were in monogamous unions. In a multivariable model, the
      variables that were independently associated with increased use of herbal
      medicine among infertile patients were being married (OR 2.55, CI 1.24-5.24),
      never conceived (OR 4.08 CI 1.86-8.96) and infertility for less than 3 years (OR
      3.52 CI 1.51-8.821). Factors that were associated with less use of herbal
      medicine among infertile women were being aged 30 years or less (OR 0.18 CI 0.07
      0.46), primary and no education (OR 0.12 CI 0.05-0.46) and living with partner
      for less than three years (OR 0.39 CI 0.16-0.93). CONCLUSIONS: The prevalence of
      herbal medicine use among women attending the infertility clinic was 76.2%.
      Herbal medicine use was associated with the participants' age, level of
      education, marital status, infertility duration, nulliparity, and duration of
      marriage. Medical care was often delayed and the majority of the participants did
      not disclose use of herbal medicines to the attending physician. Health
      professionals should enquire about use of herbal medicines. This may help in
      educating the patients about the health risks of using herbal medicine and may
      reduce delays in seeking appropriate care. Collaboration of health professionals
      with herbal medicine practitioners would help identify the common herbal
      medicines used for infertility treatment, their potential benefits and harm.

PMID- 24433550
TI  - Blood pressure tables for Chinese adolescents: justification for incorporation of
      important influencing factors of height, age and sex in the tables.
AB  - BACKGROUND: Elevated blood pressure (BP) in childhood was a predictor of
      hypertension in adulthood and contributes to the current epidemic of
      cardiovascular disease. It is necessary to identify abnormal BP in children and
      adolescents with accurate BP tables based on several crucial factors. The purpose
      of this study was to identify the important influencing factors of BP of Chinese
      adolescents. METHODS: BP, height, and body weight were assessed in 32221 normal
      weight Chinese adolescents aged 12-17 years. An equal number of 6815 subjects
      from boys and girls were individually matched by height and age to assess the
      independent effect of sex on BP; and an equal number of 1422 subjects from each
      of the age groups (12, 13, 14, 15, 16 and 17 years) were individually matched by
      sex and height to estimate the independent effect of age on BP. Height of each
      sex and age was divided into eight height groups - ~5th, ~10th, ~25th, ~50th,
      ~75th, ~90th, ~95th, and 95th ~ percentiles- and the Spearman's correlation
      between height percentiles and BP was used to examine the independent effect of
      height on BP. RESULTS: Boys had higher systolic BP (SBP) and diastolic BP (DBP)
      than girls after controlling for age and height. BP increased with age after
      controlling for sex and height. In each age group, both SBP and DBP increased
      alongside increasing height in boys and girls. CONCLUSIONS: Sex, age and height
      are all independent determinants for BP levels in Chinese adolescents. It is
      essential to incorporate these three factors for the establishment of the BP
      reference tables.

PMID- 24433551
TI  - Exploring the General Practitioner-pharmacist relationship in the community
      setting in Ireland.
AB  - OBJECTIVE: To explore the General Practitioner (GP)-pharmacist relationship, to
      gain insight into communication between the professions and evaluate opinion on
      extension of the role of the community pharmacist. METHODS: A postal
      questionnaire sent to 500 GPs and 335 community pharmacists with work addresses
      in the counties of Cork, Kerry, Tipperary, Waterford and Limerick, Ireland. KEY
      FINDINGS: An overall response rate of 56% was achieved. Clear differences of
      opinion exist between GPs and pharmacists on the extension of the role of the
      community pharmacist; pharmacist provision of vaccinations (12% of GPs in favour
      versus 78% of pharmacists), pharmacists prescribing the oral contraceptive pill
      (18% GP versus 88% pharmacist) and increasing the prescribing power of the
      pharmacist (37% GP versus 95% pharmacist). Fifty-four percent of GPs and 97% of
      pharmacists were in favour of pharmacists providing screening services, while 82%
      of GPs and 96% of pharmacists were in favour of pharmacists dealing with minor
      ailments. Seventy-three percent of GPs and 43% of pharmacists agreed that
      communication between the professions was very good. DISCUSSION: This study
      identifies a clear difference of opinion on the extension of the role of the
      community pharmacist and recognises problems in communication between the
      professions. This comes on the background of continued calls from the
      Pharmaceutical Society of Ireland for an extension of pharmacist roles and
      continued opposition from the Irish Medical Organisation to such moves. This
      study highlights the need for increased dialogue between representative
      organisations and a commitment for professional agendas to be set aside in the
      best interests of patients.

PMID- 24433554
TI  - 10 years in history.

PMID- 24433553
TI  - Diagnostic dilemma of paraneoplastic arthritis: case series.
AB  - OBJECTIVES: Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While
      presenting the demographic and laboratory features of the patients diagnosed with
      PA, this study also aims to provide possible appropriate tools to differentiate
      the PA cases from early rheumatoid arthritis (ERA). METHODS: Sixty-five patients
      with PA (male/female: 43/22) from 15 different rheumatology clinics and 50
      consecutive patients with ERA (male/female: 13/37) fulfilling the 2010 American
      College of Rheumatology (ACR) criteria for the diagnosis if the RA from Gaziantep
      Rheumatology Early Arthritis Trial (GREAT) as controls who were diagnosed at
      least 12 months before, were enrolled into study. RESULTS: Mean ages of the
      patients with PA and ERA were 50.2 +/- 15.3, and 42.7 +/- 12.3, respectively, and
      the mean ages of the patients with PA were significantly higher than the ERA.
      Unlike the ERA patients, in our case series PA was predominantly observed among
      males. Oligoarthritis was significantly higher in solid tumors in contrast to ERA
      (P = 0.001). Polyarthritis and symmetric arthritis were significantly higher in
      the ERA group in contrast to all malignancies (P = 0.001). Rheumatoid factor (RF)
      and anticyclic citrullinated peptide antibody (anti-CCP) positivity were
      significantly higher in the ERA group (each P = 0.001). Lactic dehydrogenase
      levels of hematologic malignancies were significantly higher than other groups
      (each, P = 0.001). CONCLUSIONS: ERA patients had more symmetric joint involvement
      than PA; laboratory markers could be also an alternative where there is high RF
      and anti-CCP positivity with antibody levels among the ERA patients. Finally, the
      demographic features can be used as differentiating factors; ERA was seen
      predominantly among females aged 40-59 years which refers to young adults.

PMID- 24433557
TI  - Sexual function in post-stroke patients: considerations for rehabilitation.
AB  - INTRODUCTION: While the rehabilitation goals of post-stroke patients include
      improving quality of life and returning to functional activities, the extent to
      which sexual activity is addressed as part of the standard rehabilitation process
      is unknown. Moreover, the specific sexual concerns of stroke patients, including
      the effect of stroke on intimate relationships and sexuality of the partner, the
      ability to physically engage in sex, and the effect of psychological components
      such as role identity, depression, and anxiety on sexuality, all warrant
      examination by rehabilitation professionals. AIM: The aim of this study is to
      examine the existing literature on sexuality and stroke patients in order to
      better understand how the sexual lives of stroke patients and their partners are
      affected and to provide recommendations to rehabilitation professionals for
      addressing sexuality as part of treatment. METHODS: Narrative review, PubMed,
      PEDro, ISI Web of Science, and Google Scholar databases (inception-December 2012)
      were searched for the key words "stroke," "sexual dysfunction," "sexuality,"
      "quality of life," and their combination. All relevant articles in English and
      secondary references were reviewed. MAIN OUTCOME MEASURES: We report the results
      of the literature review. RESULTS: Sexual dysfunction and decreased sexual
      satisfaction are common in the post-stroke population and are related to
      physical, psychosocial, and relational factors. However, they are not adequately
      addressed in post-stroke rehabilitation. CONCLUSIONS: As sexual function is an
      important component to quality of life and activities of daily living, physicians
      and rehabilitation specialists, including physical, occupational, and speech
      therapists, should receive training in addressing sexuality in the treatment of
      post-stroke patients. Sexologists and sex therapists should be an integral part
      of the rehabilitation team.

PMID- 24433558
TI  - Effectiveness of intracavernous delivery of adenovirus encoding Smad7 gene on
      erectile function in a mouse model of cavernous nerve injury.
AB  - INTRODUCTION: Men with erectile dysfunction (ED) respond poorly to oral
      phosphodiesterase-5 inhibitors following radical prostatectomy. Recent studies
      have reported that up-regulation of transforming growth factor-beta1 (TGF-beta1)
      and activation of the Smad signaling pathway play important roles in cavernous
      fibrosis and in the deterioration of erectile function in a mouse model of
      cavernous nerve injury (CNI) and in patients with spinal cord injury. The mothers
      against decapentaplegic homolog 7 (Smad7) is known to inhibit the phosphorylation
      of Smad2 and Smad3. AIM: To investigate the effectiveness of adenoviruses
      encoding Smad7 gene (Ad-Smad7) on erectile function in a mouse model of CNI.
      METHODS: Twelve-week-old C57BL/6J mice were used and distributed into 7 groups:
      sham operation group, untreated CNI group, and CNI groups receiving a single
      intracavernous injection of adenovirus encoding LacZ (1 * 10(8) virus particles
      [vp]/20 MUL) or adenovirus encoding Smad7 (Ad-Smad7; 1 * 10(7), 1 * 10(8), 2 *
      10(8), or 1 * 10(9) vp/20 MUL). MAIN OUTCOME MEASURES: Two weeks after bilateral
      cavernous nerve crushing and treatment, erectile function was measured by
      electrical stimulation of the cavernous nerve. The penis was harvested for
      histologic examinations and Western blot analysis. RESULTS: The highest erectile
      response was noted in CNI mice treated with Ad-Smad7 at a dose of 1 * 10(8)  vp,
      which reached up to 82-85% of sham control values. Local delivery of Ad-Smad7
      significantly decreased endothelial cell apoptosis and the production of
      extracellular matrix proteins, including plasminogen activator inhibitor-1,
      fibronectin, collagen I, and collagen IV, and induced endothelial nitric oxide
      synthase phosphorylation in the corpus cavernosum tissue of CNI mice. CONCLUSION:
      The adenovirus-mediated gene transfer of Smad7 successfully restored erectile
      function by enhancing endothelial cell function and through antifibrotic effects.
      These findings suggest that inhibition of the TGF-beta signaling pathway by use
      of Smad7 may represent a promising therapeutic strategy for ED induced by radical
      prostatectomy.

PMID- 24433560
TI  - Flaccid penile acceleration as a marker of cardiovascular risk in men without
      classical risk factors.
AB  - INTRODUCTION: Conventional cardiovascular (CV) risk factors identify only half of
      subjects with incident major adverse CV events (MACE). Hence new markers are
      needed in high CV risk subjects, as those with erectile dysfunction (ED). A role
      for dynamic peak systolic velocity (D-PSV) at penile color Doppler ultrasound
      (PCDU) has been suggested, but it is operator dependent and time consuming.
      Flaccid penile acceleration (FPA) is a PCDU parameter that reflects PSV, the
      systolic rise time (SRT), and end diastolic velocity (EDV), arithmetically
      defined as (PSV-EDV)/SRT. AIM: The study aims to verify, in a large series of ED
      patients, whether FPA has a role in predicting MACE. METHODS: A selected series
      of 1,903 patients (aged 54.6 +/- 11.7) with a suspected organic component for ED
      was retrospectively studied from January 2000 until July 2012. A subset of this
      sample (n = 622) was enrolled in a longitudinal study that ended in December
      2007. MAIN OUTCOME MEASURES: Several clinical, biochemical, and instrumental
      (PCDU) parameters were studied. RESULTS: Decreased FPA levels were associated
      with worse metabolic profile and sexual symptoms. In addition, FPA was positively
      associated with both total and calculated free testosterone. In the longitudinal
      study, unadjusted incidence of MACE was significantly associated with lower
      baseline FPA. When FPA was introduced in a multivariate model, along with D-PSV,
      after adjusting for age and Chronic Disease Score, lower FPA, but not D-PSV, was
      associated with incident MACE in lower--risk-i.e., younger (HR = 0.48 [0.23
      0.99]), nonhypertensive (HR = 0.59 [0.38-0.92]), nonobese (HR = 0.68 [0.49
      0.96]), or nondiabetic (HR = 0.67 [0.49-0.96] subjects; all P < 0.05--but not in
      higher-risk ones. FPA demonstrated a threshold effect in predicting MACE at a
      value <1.17 m/s(2) which showed a threefold increase in incidence of MACE in
      apparently lower-risk individuals. CONCLUSIONS: FPA is an easily obtained PCDU
      parameter and capable of identifying adverse metabolic and CV profiles,
      particularly in apparently lower-risk individuals with ED.

PMID- 24433559
TI  - Uric acid level and erectile dysfunction in patients with coronary artery
      disease.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a frequent complaint of elderly
      subjects and is closely associated with endothelial dysfunction and
      cardiovascular disease (CVD). Uric acid is also associated with endothelial
      dysfunction, oxidative stress, and CVD, raising the hypothesis that an increased
      serum uric acid might predict ED in patients who are at risk for coronary artery
      disease (CAD). AIM: This study aims to evaluate the association of serum uric
      acid levels with presence and severity of ED in patients presenting with chest
      pain of presumed cardiac origin. METHODS: This is a cross-sectional study of 312
      adult male patients with suspected CAD who underwent exercise stress test (EST)
      for workup of chest pain and completed a sexual health inventory for men survey
      form to determine the presence and severity of ED. Routine serum biochemistry
      (and uric acid levels) were measured. Logistic regression analysis was used to
      assess risk factors for ED. MAIN OUTCOME MEASURES: The short version of the
      International Index of Erectile Function questionnaire diagnosed ED (cutoff score
      <= 21). Serum uric acid levels were determined. Patients with chest pain of
      suspected cardiac origin underwent an EST. RESULTS: One hundred forty-nine of 312
      (47.7%) male subjects had ED by survey criteria. Patients with ED were older and
      had more frequent CAD, hypertension, diabetes and impaired renal function, and
      also had significantly higher levels of uric acid, fibrinogen, glucose, C
      reactive protein, triglycerides compared with patients without ED. Uric acid
      levels were associated with ED by univariate analysis (odds ratio = 1.36, P =
      0.002); however, this association was not observed in multivariate analysis
      adjusted for estimated glomerular filtration rate. CONCLUSION: Subjects
      presenting with chest pain of presumed cardiac origin are more likely to have ED
      if they have elevated uric acid levels.

PMID- 24433561
TI  - Prevention of recurrent ischemic priapism with ketoconazole: evolution of a
      treatment protocol and patient outcomes.
AB  - INTRODUCTION: The management of recurrent ischemic priapism (RIP) is not clearly
      defined. Ketoconazole (KTZ) is used to treat RIP and produces a temporary
      hypogonadal state to suppress sleep-related erections (SREs), which often evolve
      into episodes of ischemic priapism in this population. AIM: We review our
      experience to prevent RIP using KTZ and present our outcomes using a decreased
      dose regimen. METHODS: A retrospective chart review and phone survey of 17
      patients with RIP was performed. KTZ inhibits adrenal and gonadal testosterone
      production with a half-life of 8 hours. By suppressing testosterone levels, SREs
      are interrupted. We compared our previous protocol of three times daily (TID) KTZ
      dosing with prednisone for 6 months with our current regimen of initiating KTZ
      200 mg TID with prednisone 5 mg daily for 2 weeks and then tapering to KTZ 200 mg
      nightly for 6 months. MAIN OUTCOME MEASURES: The primary outcome was the
      prevention of RIP using KTZ. Secondary outcomes included side effects secondary
      to KTZ use and patient satisfaction. RESULTS: All men experienced daily or almost
      daily episodes of prolonged, painful erections prior to starting KTZ. The mean
      number of emergency room (ER) visits per patient prior to starting KTZ was 6.5.
      No patient required an ER visit for RIP while on KTZ. Sixteen of 17 patients
      (94%) had complete resolution of priapism while on KTZ with effects noted
      immediately after starting therapy and no reported sexual side effects attributed
      to KTZ. One man stopped therapy after 4 days because of nausea/vomiting. Fourteen
      of 16 men eventually discontinued KTZ after a median duration of 7 months. Twenty
      nine percent reported no recurrent priapic episodes after discontinuing. A total
      of 78.6% had partial or complete resolution of symptoms persisting after KTZ was
      discontinued with a mean post-treatment follow-up of 36.7 months. CONCLUSION: No
      reliable effective preventative therapy has been identified for RIP. In our
      relatively sizable single-center experience, KTZ appears to be a reasonably
      effective, safe, and inexpensive treatment to prevent RIP while preserving sexual
      function. We now recommend our tapered dose regimen listed above. After 6 months,
      we recommend stopping the medication as we have found a majority of patients will
      not need to resume nightly KTZ.

PMID- 24433562
TI  - Does sex reassignment surgery induce cerebral modifications in MTF transsexuals?

PMID- 24433563
TI  - Primary prevention of food allergy in children and adults: systematic review.
AB  - BACKGROUND: Food allergies can have serious physical, social, and financial
      consequences. This systematic review examined ways to prevent the development of
      food allergy in children and adults. METHODS: Seven bibliographic databases were
      searched from their inception to September 30, 2012, for systematic reviews,
      randomized controlled trials, quasi-randomized controlled trials, controlled
      clinical trials, controlled before-and-after studies, interrupted time series
      studies, and prospective cohort studies. Experts were consulted for additional
      studies. There were no language or geographic restrictions. Two reviewers
      appraised the studies using appropriate tools. Data were not suitable for meta
      analysis due to heterogeneity, so were narratively synthesized. RESULTS: Seventy
      four studies were included, one-third of which were of high quality. There was no
      good evidence to recommend that pregnant or breastfeeding women should change
      their diet or take supplements to prevent allergies in infants at high or normal
      risk. There were mixed findings about the preventive benefits of breastfeeding
      for infants at high or normal risk, but there was evidence to recommend avoiding
      cow's milk and substituting with extensively or partially hydrolyzed whey or
      casein formulas for infants at high risk for the first 4 months. Soy milk and
      delaying the introduction of solid foods beyond 4 months did not have preventive
      benefits in those at high or normal risk. There was very little evidence about
      strategies for preventing food allergy in older children or adults. CONCLUSIONS:
      There is much to learn about preventing food allergy, and this is a priority
      given the high societal and healthcare costs involved.

PMID- 24433564
TI  - XS: a FASTQ read simulator.
AB  - BACKGROUND: The emerging next-generation sequencing (NGS) is bringing, besides
      the natural huge amounts of data, an avalanche of new specialized tools (for
      analysis, compression, alignment, among others) and large public and private
      network infrastructures. Therefore, a direct necessity of specific simulation
      tools for testing and benchmarking is rising, such as a flexible and portable
      FASTQ read simulator, without the need of a reference sequence, yet correctly
      prepared for producing approximately the same characteristics as real data.
      FINDINGS: We present XS, a skilled FASTQ read simulation tool, flexible, portable
      (does not need a reference sequence) and tunable in terms of sequence complexity.
      It has several running modes, depending on the time and memory available, and is
      aimed at testing computing infrastructures, namely cloud computing of large-scale
      projects, and testing FASTQ compression algorithms. Moreover, XS offers the
      possibility of simulating the three main FASTQ components individually (headers,
      DNA sequences and quality-scores). CONCLUSIONS: XS provides an efficient and
      convenient method for fast simulation of FASTQ files, such as those from Ion
      Torrent (currently uncovered by other simulators), Roche-454, Illumina and ABI
      SOLiD sequencing machines. This tool is publicly available at
      http://bioinformatics.ua.pt/software/xs/.

PMID- 24433565
TI  - Imagine HEALTH: results from a randomized pilot lifestyle intervention for obese
      Latino adolescents using Interactive Guided ImagerySM.
AB  - BACKGROUND: There is an urgent need for innovative and developmentally
      appropriate lifestyle interventions to promote healthy lifestyle behaviors and to
      prevent the early onset of type 2 diabetes and cardiovascular disease risk in
      obese Latino adolescents. Guided imagery offers promise to reduce stress and
      promote lifestyle behavior change to reduce disease risk in obese adolescents.
      Our objectives were: 1) To pilot test a new 12-wk lifestyle intervention using a
      randomized trial design in obese Latino adolescents, in order to determine the
      effects of the mind-body modality of Interactive Guided ImagerySM (IGI), over and
      above those of a didactic lifestyle education, on insulin resistance, eating and
      physical activity behaviors, stress and stress biomarkers; and 2) To explore the
      role of intervention-related changes in stress and stress biomarkers on changes
      in metabolic outcomes, particularly insulin resistance. METHODS: Obese (BMI >
      95th percentile), Latino adolescents (n = 35, age 14-17) were randomized to
      receive either 12 weekly sessions of a lifestyle education plus guided imagery
      program (GI), or lifestyle education plus a digital storytelling computer program
      (DS). Between-group differences in behavioral, biological, and psychological
      outcomes were assessed using unpaired T-tests and ANCOVA in the 29 subjects who
      completed the intervention. RESULTS: The GI group demonstrated significant
      reductions in leisure sedentary behavior (p < .05) and increases in moderate
      physical activity (p < .05) compared to DS group, and a trend toward reduced
      caloric intake in GI vs DS (p = .09). Salivary cortisol was acutely reduced by
      stress-reduction guided imagery (p < .01). There were no group differences in
      adiposity, insulin resistance, perceived stress, or stress biomarkers across the
      12-week intervention, though decrease in serum cortisol over the course of the
      intervention was associated with improved insulin sensitivity (p = .03)
      independent of intervention group and other relevant co-variates. CONCLUSIONS:
      The improvements in physical activity and stress biomarkers following this pilot
      intervention support the role of guided imagery in promoting healthy lifestyle
      behavior change and reducing metabolic disease risk in obese Latino adolescent
      populations. Future investigations will be needed to determine the full effects
      of the Imagine HEALTH intervention on insulin resistance, stress, and stress
      biomarkers. TRIAL REGISTRATION: Clinicaltrials.gov Registry #: NCT01895595.

PMID- 24433566
TI  - Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese
      children.
AB  - BACKGROUND: Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic
      disorder. The prevalence of CSID in Chinese population is unknown and no single
      case has been reported. METHODS: Sucrose tolerance tests were performed in three
      children suspected of CSID. Glucose tolerance tests were performed to exclude
      glucose malabsorption. Blood glucose was measured at fasting and at 30 min, 60
      min, 120 min, and 180 min of the study. Gastrointestinal symptoms were recorded
      up to 4 hours after the study. RESULTS: From December 2008 to June 2011, three
      children, ranging from 16 to 19 months old, were referred to our tertiary
      children's hospital due to chronic watery diarrhea and failure to thrive.
      Laboratory investigations including complete blood counts, ESR, CRP, and serum
      immunoglobulins were normal. Routine stool culture for bacteria and exam for
      parasites were negative. Upper endoscopy, colonoscopy and histology were
      unremarkable. All children failed lactose-free and amino acid-based formulas. All
      three children had flat sucrose tolerance tests and began to have watery stool 2
      4 hours after feeding sucrose test solution. The glucose tolerance tests were
      normal and no children developed watery stools up to 4 hours after feeding
      glucose test solution. CONCLUSIONS: This is the first case series of CSID in
      Chinese children. The diagnosis of CSID can be made based on clinical suspicion
      and sucrose tolerance test. CSID is probably an under-diagnosed or misdiagnosed
      disease in Chinese children and should be considered in children with chronic
      watery diarrhea.

PMID- 24433567
TI  - Automated alignment-based curation of gene models in filamentous fungi.
AB  - BACKGROUND: Automated gene-calling is still an error-prone process, particularly
      for the highly plastic genomes of fungal species. Improvement through quality
      control and manual curation of gene models is a time-consuming process that
      requires skilled biologists and is only marginally performed. The wealth of
      available fungal genomes has not yet been exploited by an automated method that
      applies quality control of gene models in order to obtain more accurate genome
      annotations. RESULTS: We provide a novel method named alignment-based fungal gene
      prediction (ABFGP) that is particularly suitable for plastic genomes like those
      of fungi. It can assess gene models on a gene-by-gene basis making use of
      informant gene loci. Its performance was benchmarked on 6,965 gene models
      confirmed by full-length unigenes from ten different fungi. 79.4% of all gene
      models were correctly predicted by ABFGP. It improves the output of ab initio
      gene prediction software due to a higher sensitivity and precision for all gene
      model components. Applicability of the method was shown by revisiting the
      annotations of six different fungi, using gene loci from up to 29 fungal genomes
      as informants. Between 7,231 and 8,337 genes were assessed by ABFGP and for each
      genome between 1,724 and 3,505 gene model revisions were proposed. The
      reliability of the proposed gene models is assessed by an a posteriori
      introspection procedure of each intron and exon in the multiple gene model
      alignment. The total number and type of proposed gene model revisions in the six
      fungal genomes is correlated to the quality of the genome assembly, and to
      sequencing strategies used in the sequencing centre, highlighting different types
      of errors in different annotation pipelines. The ABFGP method is particularly
      successful in discovering sequence errors and/or disruptive mutations causing
      truncated and erroneous gene models. CONCLUSIONS: The ABFGP method is an accurate
      and fully automated quality control method for fungal gene catalogues that can be
      easily implemented into existing annotation pipelines. With the exponential
      release of new genomes, the ABFGP method will help decreasing the number of gene
      models that require additional manual curation.

PMID- 24433568
TI  - The burden, distribution and risk factors for cervical oncogenic human papilloma
      virus infection in HIV positive Nigerian women.
AB  - BACKGROUND: The expected reduction in cervical cancer incidence as a result of
      increased access to antiretroviral therapy is yet to be seen. In this study we
      investigated the effect of HIV infection and treatment on high-risk (hr) human
      papilloma virus (HPV) prevalence and distribution. METHODS: Cervical cells from
      515 (220 HIV positive and 295 HIV negative) women, recruited during community
      cervical cancer screening programme in states of Ogun and Lagos and at the
      cervical cancer screen clinic, Nigerian Institute of Medical Research Lagos were
      evaluated for the presence of 13 hr HPV genotypes by polymerase chain reaction
      based assay. RESULTS: The prevalence of high-risk HPV was 19.6% in the studied
      population. HPV 16 (3.9%), 35 (3.5%), 58 (3.3%) and 31 (3.3%) were the most
      common hr HPV infections detected. We observed that the prevalence of hr HPV was
      higher in HIV positives (24.5%) than 15.9% in HIV negative women (OR = 1.7; 95%
      CI: 1.1-2.7). A multivariate logistic regression analysis showed a lower hr HPV
      prevalence in HIV positive women on antiretroviral drugs (OR = 0.4; 95% CI: 0.3
      0.5) and with CD4 count of 500 and above (OR = 0.7; 95% CI: 0.5-0.8). A higher
      prevalence of hr HPV was also noted in HIV positive women with CD4 count < 200
      cells/mm3 (OR = 2.4; 95% CI: 1.7-5.9). CONCLUSION: HPV 16, 35, 58 and 31
      genotypes were the most common hr HPV infection in our study group, which could
      be regarded as high risk general population sample; with higher prevalence of HPV
      16 and 35 in HIV positive women than in HIV negative women. The use of
      antiretroviral drugs was found to be associated with a lower prevalence of hr HPV
      infection, compared to those not on treatment. This study raises important issues
      that should be further investigated to enable the development of robust cervical
      cancer prevention and control strategies for women in our setting.

PMID- 24433569
TI  - Intertidal population genetic dynamics at a microgeographic seascape scale.
AB  - The intertidal community is among the most physically harsh niches on earth, with
      highly heterogeneous environmental and biological factors that impose strong
      habitat selection on population abundance, genetic connectivity and ecological
      adaptation of organisms in nature. However, most genetic studies to date have
      concentrated on the influence of basin-wide or regional marine environments (e.g.
      habitat discontinuities, oceanic currents and fronts, and geographic barriers) on
      spatiotemporal distribution and composition of intertidal invertebrates having
      planktonic stages or long-distance dispersal capability. Little is known about
      sessile marine organisms (e.g. seaweeds) in the context of topographic tidal
      gradients and reproductive traits at the microgeographic scale. In this issue of
      Molecular Ecology, Krueger-Hadfield et al. () implemented an elaborate sampling
      strategy with red seaweed (Chondrus crispus) from a 90-m transect stand near
      Roscoff and comprehensively detected genome-scale genetic differentiation and
      biases in ploidy level. This study not only revealed that tidal height resulted
      in genetic differentiation between high- and low-shore stands and restricted the
      genetic exchange within the high-shore habitat, but also demonstrated that
      intergametophytic nonrandom fertilization in C. crispus can cause significant
      deviation from Hardy-Weinberg equilibrium. Such new genetic insights highlight
      the importance of microgeographic genetic dynamics and life history
      characteristics for better understanding the evolutionary processes of speciation
      and diversification of intertidal marine organisms. 

PMID- 24433570
TI  - Hybridization and the porous genome: patterns of isolation and introgression in
      manakins.
AB  - How does one species become two? What is the relative importance of selection vs.
      drift? How many genes are involved, what are their effect sizes and where are
      they located in the genome? The answers to these questions will inevitably vary
      from one species to another, but by addressing these questions in a diverse array
      of taxa, we will gradually piece together a more complete picture of how
      evolution works. In this issue of Molecular Ecology, Parchman et al. () have
      approached these questions by studying the genomic basis of differentiation along
      a hybrid zone between two Central American bird species, the golden-collared
      (Manacus vitellinus) and white-collared (Manacus candei) manakins (see Fig. ).
      Their work presents an interesting window into the evolution of this hybrid zone
      using novel analysis tools and a nice example of how to approach the study of
      population genomics in nonmodel organisms. [Figure: see text]. 

PMID- 24433571
TI  - Community genetics in the time of next-generation molecular technologies.
AB  - Understanding the interactions of co-occurring species within and across trophic
      levels provides key information needed for understanding the ecological and
      evolutionary processes that underlie biological diversity. As genetics has only
      recently been integrated into the study of community-level interactions, the time
      is right for a critical evaluation of potential new, gene-based approaches to
      studying communities. Next-generation molecular techniques, used in parallel with
      field-based observations and manipulative experiments across spatio-temporal
      gradients, are key to expanding our understanding of community-level processes.
      Here, we introduce a variety of '-omics' tools, with recent studies of plant
      insect herbivores and of ectomycorrhizal systems providing detailed examples of
      how next-generation approaches can revolutionize our understanding of
      interspecific interactions. We suggest ways that novel technologies may convert
      community genetics from a field that relies on correlative inference to one that
      reveals causal mechanisms of genetic co-variation and adaptations within
      communities. 

PMID- 24433572
TI  - Conserving genetic diversity in the honeybee: comments on Harpur et al. (2012).
AB  - The article by Harpur et al. (2012) 'Management increases genetic diversity of
      honey bees via admixture' concludes that '...honey bees do not suffer from
      reduced genetic diversity caused by management and, consequently, that reduced
      genetic diversity is probably not contributing to declines of managed Apis
      mellifera populations'. In the light of current honeybee and beekeeping declines
      and their consequences for honeybee conservation and the pollination services
      they provide, we would like to express our concern about the conclusions drawn
      from the results of Harpur et al. (2012). While many honeybee management
      practices do not imply admixture, we are convinced that the large-scale genetic
      homogenization of admixed populations could drive the loss of valuable local
      adaptations. We also point out that the authors did not account for the extensive
      gene flow that occurs between managed and wild/feral honeybee populations and
      raise concerns about the data set used. Finally, we caution against
      underestimating the importance of genetic diversity for honeybee colonies and
      highlight the importance of promoting the use of endemic honeybee subspecies in
      apiculture. 

PMID- 24433573
TI  - Admixture increases diversity in managed honey bees: reply to De la Rua et al.
      (2013).
AB  - De la Rua et al. (2013) express some concerns about the conclusions of our recent
      study showing that management increases genetic diversity of honey bees (Apis
      mellifera) by promoting admixture (Harpur et al. 2012). We provide a brief review
      of the literature on the population genetics of A. mellifera and show that we
      utilized appropriate sampling methods to estimate genetic diversity in the focal
      populations. Our finding of higher genetic diversity in two managed A. mellifera
      populations on two different continents is expected to be the norm given the
      large number of studies documenting admixture in honey bees. Our study focused on
      elucidating how management affects genetic diversity in honey bees, not on how to
      best manage bee colonies. We do not endorse the intentional admixture of honey
      bee populations, and we agree with De la Rua et al. (2013) that native honey bee
      subspecies should be conserved. 

PMID- 24433574
TI  - Testosterone improves antidepressant-emergent loss of libido in women: findings
      from a randomized, double-blind, placebo-controlled trial.
AB  - INTRODUCTION: Female sexual dysfunction is a side effect of selective serotonin
      reuptake inhibitor (SSRI)/serotonin noradrenalin reuptake inhibitor (SNRI)
      therapy. AIMS: The aim of this study is to investigate the efficacy of
      transdermal testosterone (TT) as a treatment for SSRI/SNRI-emergent loss of
      libido. METHODS: This was a double-blind, randomized, placebo-controlled study.
      Forty-four women, aged 35-55 years, on a stable dose of SSRI or SNRI with
      treatment-emergent loss of libido were randomly allocated to treatment with a TT
      patch delivering 300 mcg of testosterone/day or an identical placebo patch (Pl)
      for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was the change
      in the Sabbatsberg Sexual Self-rating Scale (SSS) total score over 12 weeks. The
      4-week frequency of Satisfactory Sexual Events (SSEs) and the Female Sexual
      Distress Scale-Revised (FSDS-R) were also measured. RESULTS: At baseline, there
      were no differences between the treatment groups. At week 12, the change in the
      SSS score did not differ between the two groups. The increase in the 4-week
      frequency of SSEs was significantly greater for the TT group than for the Pl
      group (an increase of 2.3 events vs. 0.1, P = 0.02). The between-group difference
      in the change in the FSDS-R score approached statistical significance (P = 0.06).
      The mean total serum testosterone level at 12 weeks in the TT group was 2.1
      nmol/L. No women withdrew because of androgenic adverse events. CONCLUSIONS: TT
      therapy resulted in a significant increase in the number of SSEs compared with Pl
      therapy in women with SSRI/SNRI-emergent loss of libido. The lack of improvement
      in the SSS total score may reflect lack of sensitivity of this instrument for the
      measurement of change in sexual function. This provides the first evidence that
      TT therapy may be a treatment option for women with SSRI/SNRI-emergent loss of
      libido who need to remain on their antidepressant therapy.

PMID- 24433575
TI  - Physiological and transcriptomic characterization of submergence and
      reoxygenation responses in soybean seedlings.
AB  - Complete inundation at the early seedling stage is a common environmental
      constraint for soybean production throughout the world. As floodwaters subside,
      submerged seedlings are subsequently exposed to reoxygenation stress in the
      natural progression of a flood event. Here, we characterized the fundamental
      acclimation responses to submergence and reoxygenation in soybean at the seedling
      establishment stage. Approximately 90% of seedlings succumbed during 3 d of
      inundation under constant darkness, whereas 10 d of submergence were lethal to
      over 90% of seedlings under 12 h light/12 h dark cycles, indicating the
      significance of underwater photosynthesis in seedling survival. Submergence
      rapidly decreased the abundance of carbohydrate reserves and ATP in aerial tissue
      of seedlings although chlorophyll breakdown was not observed. The carbohydrate
      and ATP contents were recovered upon de-submergence, but sudden exposure to
      oxygen also induced lipid peroxidation, confirming that reoxygenation induced
      oxidative stress. Whole transcriptome analysis recognized genome-scale
      reconfiguration of gene expression that regulates various signalling and
      metabolic pathways under submergence and reoxygenation. Comparative analysis of
      differentially regulated genes in shoots and roots of soybean and other plants
      defines conserved, organ-specific and species-specific adjustments which enhance
      adaptability to submergence and reoxygenation through different metabolic
      pathways. 

PMID- 24433576
TI  - Adherence to reduced-polluting biomass fuel stoves improves respiratory and sleep
      symptoms in children.
AB  - BACKGROUND: Symptoms of sleep apnea are markedly increased in children exposed to
      smoke from biomass fuels and are reduced by kitchen stoves that improve indoor
      biomass pollution. However, the impact of adherence to the use of improved stoves
      has not been critically examined. METHODS: Sleep-related symptom questionnaires
      were obtained from children <15 years of age in 56 families residing in the
      communities of Lliupapuquio, Andahuaylas province in Peru before and 2 years
      after installation of less-polluting Inkawasi cooking stoves. RESULTS: 82
      children with lifetime exposures to indoor fuel pollution were included. When
      compared to those alternating between both types of stoves or those using
      traditional stoves only, those children who exclusively used Inkawasi cooking
      stoves showed significant improvements in sleep and respiratory related symptoms,
      but some minor albeit significant improvements occurred when both stoves were
      concomitantly used. CONCLUSIONS: Improvements in respiratory and sleep-related
      symptoms associated with elevated indoor biomass pollution occur only following
      implementation and exclusive utilization of improved kitchen stoves.

PMID- 24433577
TI  - The genome and proteome of Serratia bacteriophage eta which forms unstable
      lysogens.
AB  - BACKGROUND: Serratia marcescens phage eta is a temperate unclassified member of
      the Siphoviridae which had been reported as containing hypermodified guanine
      residues. METHODS: The DNA was characterized by enzymatic digestion followed by
      HPLC analysis of the nucleoside composition, and by DNA sequencing and proteomic
      analysis. Its ability to form stable lysogens and integrate was also
      investigated. RESULTS: Enzymatic digestion and HPLC analysis revealed phage eta
      DNA did not contain modified bases. The genome sequence of this virus, determined
      using pyrosequencing, is 42,724 nucleotides in length with a mol% GC of 49.9 and
      is circularly permuted. Sixty-nine putative CDSs were identified of which 19
      encode novel proteins. While seven close genetic relatives were identified, they
      shared sequence similarity with only genes 40 to 69 of the phage eta genome,
      while gp1 to gp39 shared no conserved relationship. The structural proteome,
      determined by SDS-PAGE and mass spectrometry, revealed seven unique proteins.
      This phage forms very unstable lysogens with its host S. marcescens.

PMID- 24433580
TI  - Assessment of changes in brain metabolites in Indian patients with type-2
      diabetes mellitus using proton magnetic resonance spectroscopy.
AB  - BACKGROUND: The brain is a target for diabetic end-organ damage, though the
      pathophysiology of diabetic encephalopathy is still not well understood. The aim
      of the present study was to investigate the effect of diabetes on the metabolic
      profile of brain of patients having diabetes in comparison to healthy controls,
      using in-vivo magnetic resonance spectroscopy to get an insight into the
      pathophysiology of cerebral damages caused due to diabetes. METHODS: Single voxel
      proton magnetic resonance spectroscopy (1H-MRS) was performed at 1.5 T on right
      frontal, right parieto-temporal and right parieto-occipital white matter regions
      of the brain of 10 patients having type-2 diabetes along with 7 healthy controls.
      Absolute concentration of N-acetylaspartate (NAA), choline (cho), myo-inositol
      (mI), glutamate (Glu) and glutamine (Gln), creatine (Cr) and glucose were
      determined using the LC-Model and compared between the two groups. RESULTS: The
      concentration of N-acetylaspartate was significantly lower in the right frontal
      [4.35 +/-0.69 vs. 5.23 +/-0.74; p = 0.03] and right parieto-occipital region
      [5.44 +/-0.52 vs.6.08 +/-0.25; p = 0.02] of the brain of diabetics as compared to
      the control group. The concentrations of glutamate and glutamine were found to be
      significantly higher in the right frontal region of the brain [7.98 +/-2.57 vs.
      5.32 +/-1.43; P = 0.01] in diabetics. Glucose levels were found significantly
      elevated in all the three regions of the brain in diabetics as compared to the
      control group. However, no significant changes in levels of choline, myo-inositol
      and creatine were observed in the three regions of the brain examined among the
      two groups. CONCLUSIONS: 1H-MRS analysis indicates that type-2 diabetes mellitus
      may cause subtle changes in the metabolic profile of the brain. Decreased
      concentrations of NAA might be indicative of decreased neuronal viability in
      diabetics while elevated concentrations of Gln and Glu might be related to the
      fluid imbalance resulting from disruption of glucose homeostasis.

PMID- 24433582
TI  - Evaluating the impact of an intensive education workshop on evidence-informed
      decision making knowledge, skills, and behaviours: a mixed methods study.
AB  - BACKGROUND: Health professionals require a unique set of knowledge and skills in
      order to meet increasing expectations to use research evidence to inform practice
      and policy decisions. They need to be able to find, access, interpret, and apply
      the best available research evidence, along with information about patient
      preferences, clinical expertise, and the clinical context and resources, to such
      decisions. This study determined preferences for continuing education following
      an intensive educational workshop and evaluated the impact of the workshop on
      evidence informed decision making (EIDM) knowledge, skills, and behaviours.
      METHODS: An explanatory mixed methods, longitudinal study design was implemented
      among a convenience sample of various health care professionals attending the
      workshop. EIDM knowledge, skills, and behaviours were quantitatively measured at
      baseline and six month follow-up, with EIDM knowledge and skills measured
      additionally immediately following the educational workshop (post-test
      measurement). To determine participants preferences for continuing education,
      data were collected using quantitative survey (post-test measurement) and
      qualitative (individual telephone interviews after six-month follow-up) methods.
      RESULTS: EIDM knowledge and skills increased significantly from baseline to
      immediately following the intervention [5.6, 95% CI (3.7, 7.4), P < 0.001] and
      from baseline to six-month follow-up [3.7, 95% CI (2.1, 5.3), P < 0.001], with a
      significant decrease from immediately following the intervention to six-month
      follow-up [-1.9, 95% CI (-3.5, -0.3), P 0.018]. EIDM behaviours increased, but
      not significantly, from baseline to six-month follow-up [1.7, 95% CI (-0.3, 3.8),
      P 0.095]. At baseline and six-month follow-up there was a weak, non-significant
      positive correlation between EIDM knowledge and skills and EIDM behaviours (r =
      0.29, P 0.069 and r = 0.24, P 0.136, respectively). Over time there was a shift
      in preferences for timing and frequency of online continuing education
      strategies. Willingness to participate in continuing education, however, remained
      evident. CONCLUSIONS: An intensive educational workshop shows promise for
      increasing EIDM knowledge and skills. Increasing EIDM knowledge and skills may
      promote the capacity of health professionals to use research evidence when making
      practice and policy decisions and, in turn, lead to positive patient outcomes.

PMID- 24433581
TI  - A putative relay circuit providing low-threshold mechanoreceptive input to lamina
      I projection neurons via vertical cells in lamina II of the rat dorsal horn.
AB  - BACKGROUND: Lamina I projection neurons respond to painful stimuli, and some are
      also activated by touch or hair movement. Neuropathic pain resulting from
      peripheral nerve damage is often associated with tactile allodynia (touch-evoked
      pain), and this may result from increased responsiveness of lamina I projection
      neurons to non-noxious mechanical stimuli. It is thought that polysynaptic
      pathways involving excitatory interneurons can transmit tactile inputs to lamina
      I projection neurons, but that these are normally suppressed by inhibitory
      interneurons. Vertical cells in lamina II provide a potential route through which
      tactile stimuli can activate lamina I projection neurons, since their dendrites
      extend into the region where tactile afferents terminate, while their axons can
      innervate the projection cells. The aim of this study was to determine whether
      vertical cell dendrites were contacted by the central terminals of low-threshold
      mechanoreceptive primary afferents. RESULTS: We initially demonstrated contacts
      between dendritic spines of vertical cells that had been recorded in spinal cord
      slices and axonal boutons containing the vesicular glutamate transporter 1
      (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive
      afferents. To confirm that the VGLUT1 boutons included primary afferents, we then
      examined vertical cells recorded in rats that had received injections of cholera
      toxin B subunit (CTb) into the sciatic nerve. We found that over half of the
      VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating
      that they were of primary afferent origin. CONCLUSIONS: These results show that
      vertical cell dendritic spines are frequently contacted by the central terminals
      of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines
      are associated with excitatory synapses, it is likely that most of these contacts
      were synaptic. Vertical cells in lamina II are therefore a potential route
      through which tactile afferents can activate lamina I projection neurons, and
      this pathway could play a role in tactile allodynia.

PMID- 24433584
TI  - Identification of lipid synthesis and secretion proteins in bovine milk.
AB  - Lactation physiology is a process that is only partly understood. Proteomics
      techniques have shown to be useful to help advance the knowledge on lactation
      physiology in human and rodent species but have not been used as major tools for
      dairy cows, except for mastitis. In this paper, advanced non-targeted proteomics
      techniques (Filter aided sample preparation and NanoLC-Orbitrap-MS/MS) were
      applied to study the milk fat globule membrane and milk serum fraction, resulting
      in the identification of 246 proteins. Of these, 23 transporters and enzymes were
      related to lipid synthesis and secretion in mammary gland and their functions are
      discussed in detail. The identification of these intracellular transporters and
      enzymes in milk provides a possibility of using milk itself to study lipid
      synthesis and secretion pathways. This full-scale scan of milk proteins by using
      non-targeted proteomic analysis helps to reveal the important proteins involved
      in lipid synthesis and secretion for further examination in targeted studies. 

PMID- 24433583
TI  - Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with
      impaired palatal shelf elevation.
AB  - BACKGROUND: LIM domain binding protein 1 (LDB1) is a transcriptional co-factor,
      which interacts with multiple transcription factors and other proteins containing
      LIM domains. Complete inactivation of Ldb1 in mice resulted in early embryonic
      lethality with severe patterning defects during gastrulation. Tissue-specific
      deletions using a conditional knockout allele revealed additional roles of Ldb1
      in the development of the central nervous system, hematopoietic system, and
      limbs. The goal of the current study was to determine the importance of Ldb1
      function during craniofacial development in mouse embryos. RESULTS: We generated
      tissue-specific Ldb1 mutants using Wnt1-Cre, which causes deletion of a floxed
      allele in the neural crest; neural crest-derived cells contribute to most of the
      mesenchyme of the developing face. All examined Wnt1-Cre;Ldb1(fl/-) mutants
      suffered from cleft secondary palate. Therefore, we performed a series of
      experiments to investigate how Ldb1 regulated palate development. First, we
      examined the expression of Ldb1 during normal development, and found that Ldb1
      was expressed broadly in the palatal mesenchyme during early stages of palate
      development. Second, we compared the morphology of the developing palate in
      control and Ldb1 mutant embryos using sections. We found that the mutant palatal
      shelves had abnormally blunt appearance, and failed to elevate above the tongue
      at the posterior domain. An in vitro head culture experiment indicated that the
      elevation defect was not due to interference by the tongue. Finally, in the Ldb1
      mutant palatal shelves, cell proliferation was abnormal in the anterior, and the
      expression of Wnt5a, Pax9 and Osr2, which regulate palatal shelf elevation, was
      also altered. CONCLUSIONS: The function of Ldb1 in the neural crest-derived
      palatal mesenchyme is essential for normal morphogenesis of the secondary palate.

PMID- 24433585
TI  - The influence of protein fractions from bovine colostrum digested in vivo and in
      vitro on human intestinal epithelial cell proliferation.
AB  - Colostrum consists of a number of biologically active proteins and peptides that
      influence physiological function and development of a neonate. The present study
      investigated the biological activity of peptides released from first day bovine
      colostrum through in vitro and in vivo enzymatic digestion. This was assessed for
      proliferative activity using a human intestinal epithelial cell line, T84.
      Digestion of the protein fraction of bovine colostrum in vitro was conducted with
      the enzymes pepsin, chymosin and trypsin. Pepsin and chymosin digests yielded
      protein fractions with proliferative activity similar to that observed with
      undigested colostrum and the positive control foetal calf serum (FCS). In
      contrast trypsin digestion significantly (P<0.05) decreased colostral
      proliferative activity when co-cultured with cells when compared with undigested
      colostrum. The proliferative activity of undigested colostrum protein and
      abomasal whey protein digesta significantly increased (P<0.05) epithelial cell
      proliferation in comparison to a synthetic peptide mix. Bovine colostrum protein
      digested in vivo was collected from different regions of the gastrointestinal
      tract (GIT) in newborn calves fed either once (n=3 calves) or three times at 12-h
      intervals (n=3 calves). Digesta collected from the distal duodenum, jejunum and
      colon of calves fed once, significantly (P<0.05) stimulated cell proliferation in
      comparison with comparable samples collected from calves fed multiple times.
      These peptide enriched fractions are likely to yield candidate peptides with
      potential application for gastrointestinal repair in mammalian species. 

PMID- 24433586
TI  - Effect of feeding linseed oil in diets differing in forage to concentrate ratio:
      1. Production performance and milk fat content of biohydrogenation intermediates
      of alpha-linolenic acid.
AB  - To evaluate the interaction between the levels of dietary concentrate and linseed
      oil (LO) on milk fatty acid (FA) profile, 24 Holstein cows were used in a
      randomised complete block design based on days in milk, with a 2*2 factorial
      arrangement of treatments. Within each block, cows were fed one of four
      experimental diets containing 30% concentrate (LC) or 70% concentrate (HC),
      without LO (NLO) or with LO supplemented at 3% of dietary dry matter. Milk FA
      profiles were analysed with a special emphasis on the intermediates of the
      predominant trans-11, and a putative trans-13 pathways of ruminal
      biohydrogenation of cis-9, cis-12, cis-15 18:3. Feeding LO increased the
      concentrations of cis-9, cis-12, cis-15 18:3 and trans-11, cis-15 18:2 in milk
      fat, and these increases were of a higher magnitude when LO was added in HC as
      compared with LC diet (interaction of LO by concentrate). A treatment interaction
      was also observed for the level of trans-11 18:1 which was higher when feeding
      LO, but for which the increase was more pronounced with the LC as compared with
      HC diet. The concentrations of cis-15 18:1 and cis-9, trans-11, cis-15 18:3 were
      higher in cows fed LO, but feeding HC diets decreased milk fat content of cis-15
      18:1 and a tendency for a decrease in cis-9, trans-11, cis-15 18:3 was apparent.
      Feeding LO increased milk fat content of trans-13 18:1 and cis-9, trans-13 18:2,
      while the concentrations of these two isomers were not affected by the level of
      dietary concentrates. The isomer cis-9, trans-13, cis-15 18:3 has not been
      detected in any of the milk samples. In conclusion, interactions were observed
      between LO and dietary concentrates on the proportions of some intermediates of
      the trans-11 biohydrogenation pathway. The presence of trans-13 18:1 and cis-9,
      trans-13 18:2 supports the existence of a trans-13 pathway, but an 18:3
      intermediate with a trans-13 double bond has not been identified. 

PMID- 24433587
TI  - Effects of a latency period between pre-stimulation and teat cup attachment and
      periodic vacuum reduction on milking characteristics and teat condition in dairy
      cows.
AB  - The goal of the present study was to examine the suitability of a short pre
      stimulation (P) for 15 s followed by a latency period (L) of 30 s before cluster
      attachment for machine milking. In addition we tested the effect of a periodic
      reduction of the vacuum under the teat (VR) during the massage phase from 43 kPa
      to 12-15 kPa on milking characteristics and teat tissue condition. The study was
      carried out in 9 cows in a cross-over design. Animals were milked twice daily,
      and each of the 4 treatment combinations was used for six subsequent milkings
      (P+L vs. continuous P, and standard pulsation vs. VR, respectively). Milk flow
      was recorded during all experimental milkings. Longitudinal ultrasound cross
      sections of the teat were performed by B-mode ultrasound after the last milking
      of each treatment at 0, 5, and 15 min after the end of milking, respectively.
      None of the evaluated milking characteristics (total milk yield, main milking
      time, peak flow rate, average milk flow) differed between treatments. Teat
      measures as obtained by ultrasound cross sections showed no significant
      difference if individual treatments were compared at the three time points
      individually. However, teat wall thickness (TWT) tended to be smaller in VR vs.
      non-VR treatments at 5 min after milking (P=0.05). In conclusion, teat
      preparation consisting of a short stimulation followed by a latency period
      represents a similarly efficient pre-stimulation as a continuous pre-stimulation.
      VR seems to reduce the load on the teat tissue during milking and thus reduces
      the development of oedema and hence a less pronounced increase of TWT while
      milking characteristics are similar with or without VR. 

PMID- 24433588
TI  - Use of used vs. fresh cheese brines and the effect of pH and salt concentration
      on the survival of Listeria monocytogenes.
AB  - The aim of the study was to investigate how the use of fresh cheese brines
      compared with used brines and various combinations of pH and NaCl concentrations
      affected the survival of Listeria monocytogenes. Cheese brines from five
      Norwegian small scale cheese producers were analysed and showed great variations
      in pH (4.54-6.01) and NaCl concentrations (14.1-26.9 %). The survival of five
      strains of List. monocytogenes (two clinical isolates, two food isolates and one
      animal isolate) in four different cheese brines (three used and one fresh) was
      investigated. Results showed significant differences in survival both depending
      on the strains and the brines. Strains of human outbreak listeriosis cases showed
      greater ability to survive in the brines compared with food isolates and a List.
      monocytogenes reference strain (1-2 log10 difference after 200 d). All strains
      showed highest survival in the freshly prepared brine compared with the used
      brines. Molecular typing by multiple locus variable number tandem repeats
      analysis (MLVA) showed that there were no detectable alterations in the examined
      variable number tandem repeats of the genome in five strains after 200 d storage
      in any of the salt brines. Combined effects of pH (4.5, 5.25 and 6.0) and NaCl
      (15, 20 and 25 %) in fresh, filter sterilised brines on the survival of List.
      monocytogenes were examined and results showed that pathogen populations
      decreased over time in all brines. Death rates at any given NaCl concentration
      were highest at low pH (4.5) and death rates at any given pH were highest at low
      NaCl concentrations (15 %). In conclusion, the use of used brines reduced the
      survival of List. monocytogenes and a combination of low pH (4.5) and low salt
      concentrations (15 %) decreased the risk of List. monocytogenes survival compared
      with higher pH (5.25 or 6.0) and higher NaCl concentrations (20 or 25 %). 

PMID- 24433589
TI  - Ten-year prescription trends of asthma medications in the management of childhood
      wheeze.
AB  - Asthma is the most common chronic disorder of childhood. The aim of this study
      was to assess prescription trends of asthma medications to provide a measure to
      evaluate treatment practices and compliance with established international
      practice guidelines. A retrospective study of data obtained from outpatient
      prescription databases (2001-2010) of the University Children's Medical Institute
      for children aged 0-18 years was performed. The following drugs were included:
      short-acting beta-agonists (SABAs), long-acting beta-agonists in combination with
      inhaled corticosteroids (LABA-ICSs), ICS, and leukotriene receptor antagonists.
      Statistical analysis of prescription trends was performed with linear regression
      to determine the trends in prescription of controller medications. From 2001 to
      2010, the number of patients who were prescribed SABA increased significantly by
      72% (p = 0.016). The increases in ICS patient numbers and ICS/SABA drug unit
      ratios were significant only in the school-going (>5 years) age group. There was
      a trend away from the use of nebulized SABA and ICS, although this was
      statistically insignificant. LABA-ICS patient numbers decreased significantly by
      32.4% (p = 0.003), especially in preschoolers (1-5 years). There was a
      corresponding rise in montelukast patient numbers by 194.6% (p = 0.009) and
      montelukast/SABA ratio by 345.3% (p = 0.032) in preschoolers (aged 1-5 years).
      Montelukast patient numbers, but not the montelukast/SABA ratio, increased in
      school-going children. The move away from LABA-ICS combination especially in
      younger children and a tendency toward more montelukast usage is a reflection of
      practice preferences in accordance with current international guidelines in young
      children. 

PMID- 24433590
TI  - Perspectives on chronic urticaria/angioedema and its treatment.

PMID- 24433591
TI  - Quality of life in patients with urticaria and angioedema: assessing burden of
      disease.
AB  - Patients with urticaria and/or angioedema have several reasons to have a poor
      quality of life (QoL). The intensity of pruritus and density of involvement
      compromise a patient's lifestyle as well as aggravate stressors that affect
      physical and psychiatric conditions. The burden of illness is significant in not
      only costs for emergent practitioner visits, but, often, unnecessary laboratory
      testing and medication expenses. Questionnaires that assess a patient's QoL serve
      to document benefit to therapies. Objectively documenting changes that are
      important to patients with urticaria and/or angioedema allows the patients and
      clinician to accurately assess effectiveness of therapies over long periods of
      time. Specific surveys that address urticaria (CU-Q2oL and UAS) and angioedema
      (AE-QoL questionnaire) allow simplified and sensitive assessments for patients
      with the corresponding condition. Common components of appropriate surveys assess
      not only intensity of pruritus and wheals but also impact on sleep, interpersonal
      relationships, and appearances. In considering the most important aspects of
      several surveys, an example of a survey is provided that focuses on the patient's
      perception of how their urticaria and/or angioedema impacts their QoL. 

PMID- 24433592
TI  - Evidence-based diagnosis and treatment of chronic urticaria/angioedema.
AB  - Chronic urticaria/angioedema (CUA) continues to be a vexing condition for both
      patients and health care providers. Despite progress made in recent years to
      improve our understanding of the pathogenesis of CUA and its treatment, many
      patients continue to experience ongoing symptoms and impaired quality of life. In
      the overwhelming majority of cases, a definite etiology is not identified.
      Laboratory testing may be justified based on its "reassurance value"; however,
      extensive routine testing is not favorable from a cost-benefit standpoint and
      does not lead to improved patient care outcomes. The target for effective
      management is to control CUA with a combination of avoidance measures, lifestyle
      changes, and regular administration of medication. A step-care approach to
      pharmacologic management that is favorable from the standpoint of balancing the
      potential for benefit with the potential for harm can lead to substantial
      improvement in quality of life. This article will focus on achieving improved
      outcomes for patients with CUA based on evidence-directed recommendations for
      diagnosis and management. 

PMID- 24433593
TI  - Idiopathic anaphylaxis.
AB  - Idiopathic anaphylaxis is not uncommon and can be found in as many as 60% of
      patients referred to an allergist for anaphylactic events. It is an extremely
      frustrating condition for patients because they have no means of avoiding a known
      allergen and events occur spontaneously and unprovoked. The objective of this
      study was to synthesize and review the medical literature on idiopathic
      anaphylaxis and present a strategy for diagnosis, prevention, and treatment of
      episodes. A literature review was performed after a search of PubMed using the
      key words of idiopathic anaphylaxis. Idiopathic anaphylaxis is more common in
      adults than in children and in women than in men. The symptoms and signs are
      identical to those found in other causes of anaphylaxis. Perhaps the most common
      entities to be considered in the differential diagnosis are somatoform reactions.
      The two most recent advances in our ability to detect the cause are the discovery
      that episodes can be caused by mast cell-activating syndromes, systemic
      mastocytosis, and IgE to galactose-alpha-1,3-galactose. Patients experiencing
      idiopathic anaphylactic episodes should, if possible, avoid taking drugs that may
      complicate therapy or worsen a reaction. Fortunately, the vast majority of cases
      follow a benign course. Although many recurrent episodes of anaphylaxis remain
      idiopathic, recent advances in our knowledge, especially the description of mast
      cell-activating disorders and the discovery of anaphylactic reactions to
      galactose-alpha-1,3-galactose have allowed us to find causes in events that
      previously would have been classified as idiopathic. In addition, the majority of
      such patients exhibit a diminishing frequency of reactions over time and can be
      managed in a way that prevents mortality and a severe effect on their quality of
      life. 

PMID- 24433594
TI  - Intranasal corticosteroids: the role of patient preference and satisfaction.
AB  - Allergic rhinitis (AR) is a disease with a significant global burden, associated
      with many comorbidities and quality-of-life issues. Overwhelming evidence shows
      that intranasal corticosteroids are the most effective treatment for AR to
      control the disease, decrease comorbidities, and decrease costs. Poor adherence
      is a major barrier to achieving control of AR. This article addresses patient
      preferences and satisfaction regarding intranasal corticosteroids and factors
      leading to better adherence. We review and summarize the published literature.
      Factors affecting patient preference and, ultimately, adherence include a variety
      of sensory components such as odor, taste, comfort of delivery, delivery devices
      (aerosol versus aqueous) and patient cost. The intensity of adverse sensory
      attributes is negatively correlated with patient preference and the likelihood of
      adherence. Selection of an intranasal steroid (INS) with patient preference and
      satisfaction in mind can influence patient outcomes and cost. Providers need to
      assess each patient to determine which inhaled INS will lead to the best
      adherence, thereby improving outcomes in our patients and ultimately reducing the
      overall global burden of this disease. 

PMID- 24433595
TI  - Sublingual immunotherapy for aeroallergens: status in the United States.
AB  - Sublingual immunotherapy (SLIT) has been used in the treatment of allergic
      disease for nearly 30 years and is prescribed at least as frequently as
      subcutaneous immunotherapy (SCIT). Several large U.S. clinical trials using
      single allergen tablets (grass and ragweed) or extract solution (ragweed) have
      met their primary clinical efficacy outcome. In December, 2013 the Federal Drug
      Administration (FDA) Allergenic Products Advisory Committee favorably reviewed
      two grass tablet product formulations; the FDA usually follows the
      recommendations of their advisory committees. Industry-sponsored and investigator
      initiated aeroallergen SLIT clinical trials conducted in the United States are
      the focus of this article. To provide a basis for evaluation of this treatment,
      SLIT mechanisms, pharmacokinetics, efficacy as reported in systematic reviews,
      and safety are also discussed. Practical considerations of SLIT in the clinical
      setting are reviewed. These include patient instructions and adherence, which
      appear to be as poor as SCIT. Estimated treatment costs based on U.S.-licensed
      allergen extract manufacturers' list prices and doses reported to be effective in
      studies using U.S.-licensed allergen extracts or the allergen immunotherapy
      practice parameters are presented. Unmet needs, which include unknown effective
      dose for many allergen extracts, optimal schedule (daily versus other) and timing
      of treatment initiation (perennial versus precoseasonal, >=8 weeks before or just
      at the start of season), and whether epinephrine autoinjectors should be
      routinely prescribed for SLIT patients are discussed. 

PMID- 24433596
TI  - Ranking in importance of allergen extract characteristics for sublingual
      immunotherapy by Italian specialists.
AB  - The efficacy of allergen immunotherapy (AIT) is well supported by evidence from
      trials and meta-analyses. However, its actual performance in daily practice may
      be diminished by several pitfalls, including inappropriate patient selection,
      and, especially, the use of allergen extracts of insufficient quality. We
      performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate
      which criteria specialists use to choose products for sublingual immunotherapy
      (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed
      a total of 169 Italian allergists randomly chosen from a database belonging to a
      market research company (Lexis Ricerche, Milan, Italy). The survey was performed
      between October and November 2012 under the aegis of the European Center for
      Allergy Research Foundation and consisted of a questionnaire-based electronic
      survey prepared by a scientific board of 12 AIT experts. The questionnaire
      comprised two parts, the first of which contained 14 items to be ranked by each
      participant according to the importance assigned to each when choosing SLIT
      products. The physicians' rankings assigned major importance to the level of
      evidence-based validation of efficacy and safety, standardization of the product,
      efficacy based on personal experience, and defined content(s) of the major
      allergen(s) in micrograms. The results of this survey show that Italian
      allergists rank the quality-related characteristics of allergen extracts as
      highly important when choosing products for AIT. The allergists' preference for
      high-quality products should be addressed by regulatory agencies and by
      producers. 

PMID- 24433597
TI  - Health-care utilization and costs with fluticasone propionate and fluticasone
      propionate/salmeterol in asthma patients at risk for exacerbations.
AB  - Although studies have established that adding long-acting beta agonists (LABA) to
      inhaled corticosteroid (ICS) monotherapy among patients with inadequately
      controlled asthma is associated with better outcomes than increasing ICS dosage,
      outcomes with ICS versus fixed-dose ICS/LABA combination among patients with
      recent asthma exacerbation or frequent use of rescue medication are unavailable.
      This study was designed to compare health-care utilization/costs among patients
      with recent asthma exacerbation or frequent rescue medication use who received
      fluticasone propionate (FP) alone versus fixed-dose FP/salmeterol combination
      (FSC). A retrospective cohort study was conducted using a large health insurance
      data set. Patients with one or more claims with asthma diagnosis, two or more
      prescriptions for FSC (250/50- or 100/50-mg formulations) or FP (220- or 110-mg
      formulations), and one or more asthma exacerbations or five or more short-acting
      beta agonist (SABA) prescriptions within 1 year before initial receipt of study
      medications were included. Health-care utilization/costs and controller therapy
      compliance were compared for patients receiving FSC versus FP using multivariate
      regression analysis controlling for FP dose and baseline characteristics. A total
      of 7779 patients met inclusion criteria (5769, FSC, and 2010, FP) with comparable
      mean follow-up (FSC, 685 days; FP, 670 days; p = 0.151). Controlling for FP
      dosage and baseline characteristics, FSC patients had lower risks of asthma
      related exacerbations, fewer SABAs and systemic corticosteroids, higher costs of
      asthma medications and total asthma-related health care, and lower total asthma
      related health-care costs excluding study medication cost. In asthma patients
      with recent exacerbation or frequent SABA use, receipt of FSC reduced asthma
      related exacerbation risks and rescue medication use versus receipt of FP. 

PMID- 24433598
TI  - Pain perception and performance of three devices for single-site allergen skin
      testing.
AB  - Skin testing remains the preferred method for most allergists for establishing
      the presence of allergen sensitization. This study examined the performance of a
      new single-site skin test device that incorporates initial pressure to reduce the
      sensation of pain. Comparators were a conventional skin testing system and a
      smallpox needle. Twenty subjects were tested on the back, four sites with
      histamine and four sites with saline with each of the three skin testing devices.
      The single-site skin test device was applied with downward pressure, the
      conventional skin testing system, and smallpox needle (SPN) by pricking at a 45
      degrees angle. Outcomes were size and reproducibility of the skin test reactions
      and discomfort, as graded by the subject. The whealing responses to histamine
      were larger with the conventional skin testing system than with the single-site
      skin test device and both produced larger wheals than the SPN. The conventional
      skin testing system also produced greater intrasubject variability. Only the
      conventional skin testing system produced wheals of >3 mm with saline. There was
      no significant difference in perception of pain, which was low with all three
      devices. All three devices were well tolerated, without a significant difference
      in perception of discomfort. Testing with histamine revealed differences in wheal
      size and reproducibility among the three devices and testing with saline revealed
      differing likelihood of inducing a significantly sized wheal. 

PMID- 24433599
TI  - Effect of prolonged breast-feeding on risk of atopic dermatitis in early
      childhood.
AB  - The effect of breast-feeding on the risk of developing atopic disease remains
      controversial. This study is an investigation of the effect of breast-feeding on
      current atopic dermatitis (AD) among Korean children. This cross-sectional study
      of children's histories of current AD and environmental factors was completed by
      the subjects' parents. The subjects included 10,383 children aged 0-13 years in
      Seoul, Korea, in 2008. The diagnostic criteria of the International Study of
      Asthma and Allergies in Childhood were applied in this study. Adjustments were
      performed for age, gender, maternal education, smoking in the household,
      relocation to a new house within 1 year of birth, and parental history of atopic
      disease. After adjustment for confounders, age and duration of maternal education
      were found to be inversely associated with the prevalence of AD. Among subjects
      aged <=5 years, the prevalence of AD was positively associated with the duration
      of breast-feeding (p < 0.001). However, there was no significant association
      between AD and breast-feeding among children >5 years of age. Regardless of
      parental history of atopic diseases, breast-feeding >12 months was a significant
      risk factor for AD. The effect of breast-feeding differed by age group. Prolonged
      breast-feeding increased the risk of AD in children <5 years of age, regardless
      of parental history of atopic diseases. 

PMID- 24433600
TI  - Anaphylaxis/angioedema caused by honey ingestion.
AB  - Honey allergy is a very rare, but serious health condition. In this study, we
      presented six patients who described systemic allergic reactions after ingestion
      of honey. Three of the six patients had suffered from anaphylaxis. Honey-specific
      IgE was measured and skin-prick tests for honey were performed to diagnose honey
      allergy. The results of honey-specific IgE of all patients were positive. Four
      patients had high serum-specific IgE for honey bee venom and two of five patients
      had also experienced anaphylaxis due to bee stings. Skin-prick tests with honey
      and pollens were positive in five patients. Honey is one of the foods that can
      cause severe systemic reactions. Specific IgE and skin-prick tests are helpful
      for the diagnosis of honey allergy. 

PMID- 24433601
TI  - Schnitzler Syndrome.
AB  - A 48-year-old man with typical features of Schnitzler Syndrome is presented,
      followed by a discussion of the pathogenesis and clinical aspects of this rare
      disease. Some of the challenges we and others have faced in diagnosing and
      treating this disease are also discussed. Clinical pearls and pitfalls are
      emphasized to aid clinicians from varying specialties in recognizing this
      syndrome and providing appropriate therapy. Schnitzler Syndrome is associated
      with high morbidity and increased risk of lymphoproliferative disorders. Accurate
      diagnosis is vital in restoring quality of life and ensuring appropriate long
      term monitoring. 

PMID- 24433602
TI  - High-grade fever and pancytopenia in an adult patient with common variable immune
      deficiency.
AB  - Fever of unknown origin in patients with common variable immune deficiency (CVID)
      can be caused by variety of infectious, autoimmune, or malignancy-related
      etiologies. We present a 52-year-old man with history of CVID, who presented with
      3 weeks of persistent high-grade fevers. During admission, he developed severe
      pancytopenia with shock and multiorgan failure. An extensive workup was performed
      for typical and atypical infections, autoimmune pathologies, and malignancy. His
      peripheral blood smear showed marked anisocytosis and poikilocytosis with
      elevated atypical lymphocytes. Flow cytometry showed markedly elevated CD8
      counts, with abnormal CD4/CD8 ratio. Monospot test was negative but real-time
      polymerase chain reaction showed high Epstein-Barr virus load. Initial clinical
      suspicion was high for bacterial infections including pneumonia and acute
      sinusitis complicated by bacteremia and sepsis. Hematologic malignancy was also
      high on the differentials because of presence of rapidly progressive
      pancytopenia. The final diagnosis in this case illustrates a rare but potentially
      fatal disease that can present in CVID patients with persistent fevers and
      pancytopenia and can be refractory to standard treatment regimen. Because allergy
      and immunology physicians commonly treat CVID patients, they should be aware of
      this disease condition including pathophysiology, clinical presentation,
      laboratory workup, and treatment options. 

PMID- 24433603
TI  - For the patient.

PMID- 24433604
TI  - Frequency and risk of in-stent stenosis following pulmonary artery stenting.
AB  - Peripheral and central pulmonary artery (PA) stenoses can result in right
      ventricular hypertension, dysfunction, and death. Percutaneous PA angioplasty and
      stent placement relieve obstruction acutely, but patients frequently require
      reintervention. Within a heterogeneous patient population with PA stents referred
      for catheterization because of noninvasive signs of PA obstruction, we have
      observed that in-stent stenosis (ISS) occurs commonly in some groups, challenging
      previous reports that this phenomenon occurs infrequently. We set out to evaluate
      the incidence and demographics of patients with previous PA stent placement who
      develop ISS. Consecutive patients with previously placed stents presenting for
      catheterization and undergoing PA angiography were reviewed (104 patients, 124
      cases). We defined ISS angiographically, as a 25% narrowing of the contrast
      filled lumen relative to the fluoroscopically apparent stent diameter at any site
      along the length of the stent. For inclusion, we required that the stenotic
      segment be narrower or equal in size to the distal vessel. ISS was diagnosed in
      24% of patients, with the highest incidence among patients with tetralogy of
      Fallot and multiple aortopulmonary collaterals, Williams syndrome, or Alagille
      syndrome. In conclusion, ISS after PA stent placement is a more frequent problem
      than previously reported, and patients with inherently abnormal PAs are
      disproportionately affected. Increased clinical surveillance after stent
      placement and investigation of innovative preventive strategies may be indicated.

PMID- 24433605
TI  - Migraine and coronary microvascular dysfunction: what about the insulting factor
      for both cerebral and coronary endothelia?

PMID- 24433606
TI  - Atherosclerosis: diagnose locally, treat globally.

PMID- 24433607
TI  - Effect of coronary artery calcium as a subclinical atherosclerosis measure on
      cardiovascular events or other causes of death.

PMID- 24433608
TI  - Low-voltage QRS and amplitude attenuation in Takotsubo syndrome: just an
      intriguing hypothesis or potential preangiographic markers?

PMID- 24433609
TI  - Motivational interviewing as a smoking cessation strategy with nurses: an
      exploratory randomised controlled trial.
AB  - BACKGROUND: Despite the important role that health professionals have in reducing
      tobacco use, many have a smoking habit themselves. The prevalence of smoking is
      particularly high among nurses. OBJECTIVE: To test the efficacy, acceptability
      and feasibility of a motivational interviewing (MI) based smoking cessation
      intervention with nurses. DESIGN: Two group parallel experimental design with
      random allocation to groups. SETTING: A large teaching hospital in the North of
      Spain. PARTICIPANTS: Nurses who smoked (n=30) were randomised into two groups:
      motivational interviewing based intervention (n=15) and usual care (n=15).
      METHODS: Motivational interviewing based intervention consisted of four
      individual MI sessions. Usual care consisted of brief advice. Variables
      considered to assess efficacy were biochemically verified smoking cessation, mean
      cigarettes smoked, stages of change, self-efficacy and depression score.
      Variables to assess acceptability and feasibility included participant
      satisfaction, adherence to MI, and duration of sessions. Data were collected at:
      baseline, end of intervention and three months after the end of the intervention.
      RESULTS: At three month follow up, compared with the control group, more nurses
      in the intervention group had quit (absolute difference 33.3%; 95% confidence
      interval [CI] 2.6-58.2). In the nurses who did not quit, there was no significant
      difference between the intervention and control groups in the number of
      cigarettes smoked per day, although progress in the stages of change was greater
      in the intervention group compared to the control group. Measures of
      acceptability and feasibility indicated good satisfaction with the intervention,
      with high levels of attendance and completion. CONCLUSION: This study found a
      beneficial effect of motivational interviewing on nurses' smoking cessation. The
      intervention was acceptable for nurses and a number of aspects were identified
      that need to be considered prior to conducting a larger scale in order to
      optimise the intervention. Using MI might be a novel approach to the problem of
      health professionals who smoke.

PMID- 24433610
TI  - Bioengineering in platelet biology.

PMID- 24433611
TI  - Cardiac involvement in mixed connective tissue disease: a systematic review.
AB  - OBJECTIVE: To report the clinical characteristic of cardiac disease in patients
      with mixed connective tissue disease (MCTD). METHOD: We identified published case
      series that reported cardiac manifestations of patients with MCTD by searching
      the PubMed database using the search terms "mixed connective tissue disease". We
      identified 11 case series that met our eligibility criteria. RESULT: 616 patients
      were included. Prevalence of cardiac involvement varied from 13% to 65% depending
      on patient selection and method used for detection. Pericarditis was the most
      common cardiac diagnosis with a prevalence of 30% and 43% in two prospective
      studies. Non-invasive cardiac tests, including electrocardiogram and
      echocardiogram, detected subclinical cardiac abnormalities in 6%-38% of patients.
      These abnormalities included conduction abnormalities, pericardial effusion and
      mitral valve prolapse. Diastolic dysfunction and accelerated atherosclerosis were
      well-documented in a case-control study. Three prospective studies revealed an
      overall mortality of 10.4% over the period of follow-up of 13-15 years. 20% of
      the mortality was directly attributable to cardiac cause. CONCLUSION: Cardiac
      involvement was common among patients with MCTD though the involvement was often
      clinically inapparent. Non-invasive cardiac tests might have a role for
      subclinical disease screening for early diagnosis and timely treatment as cardiac
      involvement was one of the leading causes of mortality.

PMID- 24433612
TI  - Remote ischemic preconditioning does not improve the clinical outcomes in
      patients undergoing coronary artery bypass grafting: a meta-analysis of
      randomized controlled trials.

PMID- 24433613
TI  - Impact of diastolic wall stress on the diagnostic value of visually interpreted
      dobutamine stress MR imaging.

PMID- 24433614
TI  - Should we systematically screen for peripheral arterial aneurysms in all patients
      with Marfan syndrome?

PMID- 24433615
TI  - High BNP levels in rheumatoid arthritis are related to inflammation but not to
      left ventricular abnormalities: a prospective case-control study.

PMID- 24433616
TI  - Survival based on patient selection for heart transplant in adults with
      congenital heart disease: a multi-institutional study.

PMID- 24433617
TI  - The risk of adverse cardiac events following minor surgery under discontinuation
      of all antiplatelet therapy in patients with prior drug-eluting stent
      implantation.

PMID- 24433618
TI  - Stable microvascular angina: instrumental evaluation of coronary microvascular
      dysfunction with coronary angiography and myocardial scintigraphy.

PMID- 24433619
TI  - Galectin-3 expression in cardiac remodeling after myocardial infarction.

PMID- 24433620
TI  - Comprehensive analysis of intravascular ultrasound and angiographic morphology of
      culprit lesions between ST-segment elevation myocardial infarction and non-ST
      segment elevation acute coronary syndrome.
AB  - BACKGROUND: Some plaques lead to ST-segment elevation myocardial infarction
      (STEMI), whereas others cause non-ST-segment elevation acute coronary syndrome
      (NSTEACS). We used angiography and intravascular ultrasound (IVUS) to investigate
      the difference of culprit lesion morphologies in ACS. METHODS: Consecutive 158
      ACS patients whose culprit lesions were imaged by preintervention IVUS were
      enrolled (STEMI=81; NSTEACS=77). IVUS and angiographic findings of the culprit
      lesions, and clinical characteristics were compared between the groups. RESULTS:
      There were no significant differences in patients' characteristics except for
      lower rate of statin use in patients with STEMI (20% vs 44%, p=0.001). Although
      angiographic complex culprit morphology (Ambrose classification) and thrombus
      were more common in STEMI than in NSTEACS (84% vs 62%, p=0.002; 51% vs 5%,
      p<0.0001, respectively), SYNTAX score was lower in STEMI (8.6 +/- 5.4 vs 11.5 +/-
      7.1, p=0.01). In patients with STEMI, culprit echogenicity was more hypoechoic
      (64% vs 40%, p=0.01), and the incidence of plaque rupture, attenuation and
      "microcalcification" were significantly higher (56% vs 17%, p<0.0001; 85% vs 69%,
      p=0.01; 77% vs 61%, p=0.04, respectively). Furthermore, the maximum area of
      ruptured cavity, echolucent zone and arc of microcalcification were significantly
      greater in STEMI compared with NSTEACS (1.80 +/- 0.99 mm(2) vs 1.13 +/- 0.86
      mm(2), p=0.006; 1.52 +/- 0.74 mm(2) vs 1.21 +/- 0.81 mm(2), p=0.004; 99.9 +/-
      54.6 degrees  vs 77.4 +/- 51.2 degrees , p=0.01, respectively). Quantitative IVUS
      analysis showed that vessel and plaque area were significantly larger at minimum
      lumen area site (16.6 +/- 5.4 mm(2) vs 14.2 +/- 5.5 mm(2), p=0.003; 13.9 +/- 5.1
      mm(2) vs 11.6 +/- 5.2 mm(2), p=0.003, respectively). CONCLUSION: Morphological
      feature (outward vessel remodeling, plaque buildup and IVUS vulnerability of
      culprit lesions) might relate to clinical presentation in patients with ACS.

PMID- 24433621
TI  - Thrombin induced platelet-fibrin clot strength measured by thrombelastography is
      a novel marker of platelet activation in acute myocardial infarction.

PMID- 24433622
TI  - Biphasic hepatitis A with severe cholestasis and thrombocytopenic purpura in an
      HIV-1-infected male patient.

PMID- 24433623
TI  - Policy changes to implement intramural sports in North Carolina middle schools:
      simulated effects on sports participation rates and physical activity intensity,
      2008-2009.
AB  - INTRODUCTION: Extracurricular school sports programs can provide adolescents,
      including those who are economically disadvantaged, with opportunities to engage
      in physical activity. Although current models favor more exclusionary
      interscholastic sports, a better understanding is needed of the potential effects
      of providing alternative school sports options, such as more inclusive intramural
      sports. The purpose of this study was to simulate the potential effect of
      implementing intramural sports programs in North Carolina middle schools on both
      the rates of sports participation and on energy expenditure related to physical
      activity levels. METHODS: Simulations were conducted by using a school-level data
      set developed by integrating data from multiple sources. Baseline rates of sports
      participation were extrapolated from individual-level data that were based on
      school-level characteristics. A regression model was estimated by using the
      simulated baseline school-level sample. Participation rates and related energy
      expenditure for schools were calculated on the basis of 2 policy change
      scenarios. RESULTS: Currently, 37.2% of school sports participants are
      economically disadvantaged. Simulations suggested that policy changes to
      implement intramural sports along with interscholastic sports could result in
      more than 43,000 new sports participants statewide, of which 64.5% would be
      economically disadvantaged students. This estimate represents a 36.75% increase
      in economically disadvantaged participants. Adding intramural sports to existing
      interscholastic sports programs at all middle schools in North Carolina could
      have an annual effect of an additional 819,892.65 kilogram calories expended
      statewide. CONCLUSION: Implementing intramural sports may provide economically
      disadvantaged students more access to sports, thus reducing disparities in access
      to school sports while increasing overall physical activity levels among all
      children.

PMID- 24433624
TI  - Prevalence of smoke-free car and home rules in Maine before and after passage of
      a smoke-free vehicle law, 2007-2010.
AB  - INTRODUCTION: This is the first study to examine the prevalence of self-reported
      smoke-free rules for private cars and homes before and after the passage of a
      smoke-free vehicle law. METHODS: Data were examined for 13,461 Maine adults aged
      18 or older who participated in the Behavioral Risk Factor Surveillance System, a
      state-based telephone survey covering health topics. Self-reported smoke-free car
      and home rules, smoking behavior, and demographic variables of age, sex,
      education, income, and children in household were analyzed for prevalence before
      and after the state's smoke-free vehicle law was passed. RESULTS: Prevalence of
      smoke-free car and home rules was significantly higher after Maine's smoke-free
      vehicle law was passed in the state (P = .004 for car rules and P = .009 for home
      rules). Variations in smoking rules differed by smoking and demographic
      variables. People with household incomes of less than $20,000 saw an increase of
      14.3% in smoke-free car rules; overall, those with annual incomes of less than
      $20,000 and those with less than a high school education reported a lower
      prevalence of smoke-free car rules both before and after the law was passed than
      did people with higher incomes and higher education levels. The prevalence of
      smoke-free home rules after the law was implemented was higher among those with 4
      or more years of college education than among those with lower levels of
      education (P = .02). CONCLUSION: The prevalence of smoke-free car and home rules
      among Maine adults was significantly higher after the passage of a statewide
      smoke-free vehicle law. This apparent change in smoke-free rule prevalence may be
      indicative of changing social norms related to the unacceptability of secondhand
      smoke exposure.

PMID- 24433625
TI  - Recommendations for a culturally relevant Internet-based tool to promote physical
      activity among overweight young African American women, Alabama, 2010-2011.
AB  - INTRODUCTION: Innovative approaches are needed to promote physical activity among
      young adult overweight and obese African American women. We sought to describe
      key elements that African American women desire in a culturally relevant Internet
      based tool to promote physical activity among overweight and obese young adult
      African American women. METHODS: A mixed-method approach combining nominal group
      technique and traditional focus groups was used to elicit recommendations for the
      development of an Internet-based physical activity promotion tool. Participants,
      ages 19 to 30 years, were enrolled in a major university. Nominal group technique
      sessions were conducted to identify themes viewed as key features for inclusion
      in a culturally relevant Internet-based tool. Confirmatory focus groups were
      conducted to verify and elicit more in-depth information on the themes. RESULTS:
      Twenty-nine women participated in nominal group (n = 13) and traditional focus
      group sessions (n = 16). Features that emerged to be included in a culturally
      relevant Internet-based physical activity promotion tool were personalized
      website pages, diverse body images on websites and in videos, motivational
      stories about physical activity and women similar to themselves in size and body
      shape, tips on hair care maintenance during physical activity, and online social
      support through social media (eg, Facebook, Twitter). CONCLUSION: Incorporating
      existing social media tools and motivational stories from young adult African
      American women in Internet-based tools may increase the feasibility,
      acceptability, and success of Internet-based physical activity programs in this
      high-risk, understudied population.

PMID- 24433626
TI  - Prevalence of chronic conditions among Medicare Part A beneficiaries in 2008 and
      2010: are Medicare beneficiaries getting sicker?
AB  - INTRODUCTION: Medicare beneficiaries who have chronic conditions are responsible
      for a disproportionate share of Medicare fee-for-service expenditures. The
      objective of this study was to analyze the change in the health of Medicare
      beneficiaries enrolled in Part A (hospital insurance) between 2008 and 2010 by
      comparing the prevalence of 11 chronic conditions. METHODS: We conducted
      descriptive analyses using the 2008 and 2010 Chronic Conditions Public Use Files,
      which are newly available from the Centers for Medicare and Medicaid Services and
      have administrative (claims) data on 100% of the Medicare fee-for-service
      population. We examined the data by age, sex, and dual eligibility (eligibility
      for both Medicare and Medicaid). RESULTS: Medicare Part A beneficiaries had more
      chronic conditions on average in 2010 than in 2008. The percentage increase in
      the average number of chronic conditions was larger for dual-eligible
      beneficiaries (2.8%) than for nondual-eligible beneficiaries (1.2%). The
      prevalence of some chronic conditions, such as congestive heart failure, ischemic
      heart disease, and stroke/transient ischemic attack, decreased. The deterioration
      of average health was due to other chronic conditions: chronic kidney disease,
      depression, diabetes, osteoporosis, rheumatoid arthritis/osteoarthritis. Trends
      in Alzheimer's disease, cancer, and chronic obstructive pulmonary disease showed
      differences by sex or dual eligibility or both. CONCLUSION: Analyzing the
      prevalence of 11 chronic conditions by using Medicare claims data provides a
      monitoring tool that can guide health care providers and policy makers in
      devising strategies to address chronic conditions and rising health care costs.

PMID- 24433628
TI  - Relationship between massive chronic rotator cuff tear pattern and loss of active
      shoulder range of motion.
AB  - BACKGROUND: Management of massive chronic rotator cuff tears remains
      controversial, with no clearly defined clinical presentation as yet. The purpose
      of the study was to evaluate the effect of tear size and location on active
      motion in patients with chronic and massive rotator cuff tears with severe muscle
      degeneration. METHODS: One hundred patients with massive rotator cuff tears
      accompanied by muscle fatty infiltration beyond Goutallier stage 3 were
      prospectively included in this study. All patients were divided into 5 groups on
      the basis of tear pattern (supraspinatus, superior subscapularis, inferior
      subscapularis, infraspinatus, and teres minor). Active range of shoulder motion
      was assessed in each group and differences were analyzed. RESULTS: Active
      elevation was significantly decreased in patients with 3 tear patterns involved.
      Pseudoparalysis was found in 80% of the cases with supraspinatus and complete
      subscapularis tears and in 45% of the cases with tears involving the
      supraspinatus, infraspinatus, and superior subscapularis. Loss of active external
      rotation was related to tears involving the infraspinatus and teres minor; loss
      of active internal rotation was related to tears of the subscapularis.
      CONCLUSIONS: This study revealed that dysfunction of the entire subscapularis and
      supraspinatus or 3 rotator cuff muscles is a risk factor for pseudoparalysis. For
      function to be preserved in patients with massive chronic rotator cuff tears, it
      may be important to avoid fatty infiltration with anterior extension into the
      lower subscapularis or involvement of more than 2 rotator cuff muscles.

PMID- 24433627
TI  - The role of mechanical resonance in the neural control of swimming in fishes.
AB  - The bodies of many fishes are flexible, elastic structures; if you bend them,
      they spring back. Therefore, they should have a resonant frequency: a bending
      frequency at which the output amplitude is maximized for a particular input.
      Previous groups have hypothesized that swimming at this resonant frequency could
      maximize efficiency, and that a neural circuit called the central pattern
      generator might be able to entrain to a mechanical resonance. However, fishes
      swim in water, which may potentially damp out many resonant effects.
      Additionally, their bodies are elongated, which means that bending can occur in
      complicated ways along the length of the body. We review previous studies of the
      mechanical properties of fish bodies, and then present new data that demonstrate
      complex bending properties of elongated fish bodies. Resonant peaks in amplitude
      exist, but there may be many of them depending on the body wavelength.
      Additionally, they may not correspond to the maximum swimming speed. Next, we
      describe experiments using a closed-loop preparation of the lamprey, in which a
      preparation of the spinal cord is linked to a real-time simulation of the muscle
      and body properties, allowing us to examine resonance entrainment as we vary the
      simulated resonant frequency. We find that resonance entrainment does occur, but
      is rare. Gain had a significant, though weak, effect, and a nonlinear muscle
      model produced resonance entrainment more often than a linear filter. We
      speculate that resonance may not be a critical effect for efficient swimming in
      elongate, anguilliform swimmers, though it may be more important for stiffer
      carangiform and thunniform fishes. 

PMID- 24433629
TI  - Surveillance of Barrett's esophagus: why biopsy if you can endomicroscopy.

PMID- 24433630
TI  - Improving the efficiency of Barrett's esophagus management: do biomarkers hit the
      mark?

PMID- 24433631
TI  - Life after fellowship: private practice versus academics-the low down.

PMID- 24433632
TI  - Response.

PMID- 24433633
TI  - ERCP in cholangitis.

PMID- 24433634
TI  - Infected pancreatic pseudocyst of spleen successfully treated by combined
      endoscopic transpapillary stent placement and transmural aspiration.

PMID- 24433635
TI  - Predictive qualitative risk model of bovine rabies occurrence in Brazil.
AB  - Bovine rabies remains endemic in Brazil and despite control efforts, the disease
      still spreads insidiously. The main vector is the hematophagous bat, Desmodus
      rotundus. The present work aimed to create a predictive qualitative model of the
      occurrence of bovine rabies in each municipality in 25 of the 27 Brazilian
      States. The risk of rabies transmission from bats to bovine was estimated using
      decision-tree models of receptivity and vulnerability. Questionnaires, which
      covered a number of questions related to the surveillance of possible risk
      factors, such as bovine rabies outbreaks in the previous year, the presence of
      bat roosts, bat rabies positivity and environmental changes, were sent to the
      local veterinary units of each State. The bovine density and geomorphologic
      features were obtained from national databases and geographic information
      systems. Of the 433 municipalities presenting bovine rabies outbreaks in 2010,
      178 (41.1%) were classified by the model as high risk, 212 (49.0%) were
      classified as moderate risk, 25 (5.8%) were classified as low risk, whereas the
      risk was undetermined in 18 municipalities (4.1%). An ROC curve was built to
      determine if the risk evaluated by the model could adequately discriminate
      between municipalities with and without rabies occurrence in future years. The
      risk estimator for the year 2011 was classified as moderately accurate. In the
      future, these models could allow the targeting of rabies control efforts, with
      the adoption of control measures directed to the higher risk locations and the
      optimization of the field veterinary staff deployment throughout the country.
      Additionally, efforts must be made to encourage continuous surveillance of risk
      factors. 

PMID- 24433636
TI  - Special issue: Schwabe Symposium 2012: Introduction.

PMID- 24433637
TI  - Impact of foot-and-mouth disease on pork and chicken prices in Central Luzon,
      Philippines.
AB  - Central Luzon is the number one pig-producing region in the Philippines and was
      affected by Foot-and-Mouth disease (FMD) in 1995. In this paper, the impact of
      FMD on the Central Luzon meat market from 1995 to 1999 was examined. Employing
      the error correction model (ECM) and historical decomposition, the impact of FMD
      on the Central Luzon pork and chicken meat market was quantified. The following
      findings were observed: (a) pig farm and pork wholesale prices dropped 11.8% and
      15.7%, respectively, after the initial FMD outbreaks in January, 1995; (b) in
      February, 1995, chicken farm and wholesale prices declined by 21.1% and 14.2%,
      respectively (while chicken retail prices also went down by 10.5%); (c) the
      margins of pig and chicken traders were also adversely affected at some point;
      and (d) FMD caused changes of dynamic interdependence among prices by meat type
      at different levels of the meat supply chain. This study makes several
      contributions to the literature on the impact of FMD outbreaks. This study is the
      first that simultaneously investigates the impact of FMD outbreaks on meat
      prices, price margins along the supply chain, and price interdependence in the
      meat system in Central Luzon, Philippines. Also, the Philippine pork industry is
      dominated by backyard farmers rather than the predominantly large commercial pig
      farmers existing in developed countries. Secondly, it yielded the novel finding
      of price decline in both pig and chicken prices as a result of the FMD outbreaks.
      And lastly, the study showed that the profit margins of the pig traders, pork
      traders, chicken traders and chicken meat traders were also negatively affected
      by the FMD outbreaks in January 1995. However, over the long term, the price
      margins of pork traders were more severely affected in contrast to that of the
      other traders' profits. 

PMID- 24433638
TI  - Oral antimicrobials increase antimicrobial resistance in porcine E. coli--a
      systematic review.
AB  - Administration of antimicrobials to livestock increases the risk of antimicrobial
      resistance (AMR) in commensal bacteria. Antimicrobials in pig production are
      usually administered per pen via feed which implies treatment of sick alongside
      with healthy animals. The objective of this systematic literature review was to
      investigate the effect of orally administered antimicrobials on AMR in
      Escherichia coli of swine. Studies published in peer reviewed journals were
      retrieved from the international online databases ISI Web of Knowledge, PubMed,
      Scopus and the national electronic literature data base of Deutsches Institut fur
      Medizinische Dokumentation und Information. The studies were assessed using the
      eligibility criteria English or German language, access to full paper version,
      defined treatment and control group (initial value or non-treatment) as well as
      administration and resistance testing of the same antimicrobial class. In the
      qualitative synthesis, only studies were included presenting the summary measures
      odds ratio or prevalence of resistance, the category of the applied antimicrobial
      and the dosage. An effect of the antimicrobial on AMR in E. coli was evaluated as
      an "increase", "no effect" or "decrease" if the odds or alternatively the
      prevalence ratio were >1.0, 1.0 or <1.0, respectively. Eleven studies, describing
      36 different trials, fulfilled the eligibility criteria and were finally
      assessed. An increase of AMR in E. coli was found in 10 out of 11 trials
      comparing AMR after with AMR prior to oral treatment and in 22 of the 25 trials
      comparing orally treated with untreated groups. Effects expressed as odds or
      prevalence ratios were highest for the use of aminoglycosides, quinolones and
      tetracycline. There was no clear association between the reported dosage and AMR
      towards tetracycline. Information on antimicrobial substance and dosage was
      missing in 4 and 5 of the 11 finally selected studies. The 36 identified trials
      were inhomogenous in usage and provision of information on sample size. Oral
      administration of antimicrobials increases the risk of AMR in E. coli from swine.
      There is however a lack of studies on the impact of dosage and longitudinal
      effects of treatment. The published studies have a number of issues concerning
      their scientific quality. More high quality research is needed to better address
      and quantifiy the effect of orally administered antimicrobials on AMR in swine. 

PMID- 24433639
TI  - Use of monthly collected milk yields for the detection of the emergence of the
      2007 French BTV epizootic.
AB  - Two culicoides-borne diseases, Bluetongue (BTV) and Schmallenberg, have emerged
      in the European cattle population since 2006. Other diseases transmitted by these
      vectors could emerge. This justifies the development of syndromic surveillance
      programs whereby one or several indicators would be routinely monitored for the
      early detection of emerging diseases. The aim of this study was to evaluate milk
      yield from milk recording in dairy cattle as an indicator to be included in an
      emerging disease surveillance system. It was hypothesized that emergences would
      result in episodes of low milk production clustered in space and time. The 2007
      BTV epizootic in France was used as a case study. Because it had already emerged
      in neighbouring countries, the disease emergence was expected and notification
      was mandatory. Herd-test-day milk productions were predicted for the entire
      country for 2006 and 2007 from herd historical data using linear mixed models.
      The differences between observed and predicted milk productions were averaged per
      week and per municipality and used as input for a space-time prospective scan
      statistic. Log likelihood ratios (LLR) associated with clusters were used to
      define alarms. The threshold chosen was a trade-off between detection timeliness
      and the number of false alarms per week. The first four BTV notifications
      occurred on the 12th (two notifications), 13th and 27th of July 2007. The 12th of
      July was considered to be the date of emergence. Alarms occurring before the 1st
      of March 2007 were considered to be false alarms. Using an LLR of 50, there were
      an average of 1.7 false alarms per week and the BTV emergence was detected seven
      weeks after emergence. Using an LLR of 100, there were an average of 0.8 false
      alarms per week and the BTV emergence was detected 9 weeks after emergence.
      Detection may have been delayed because of a discontinuation of milk recording
      between mid-July and mid-August. The first cluster with an LLR>100 located in the
      emergence area was further investigated. A difference between observed and
      predicted production of >1 kg/cow/day was observed around the time of emergence.
      However, a difference of equal magnitude was observed during the year preceding
      the outbreak. Milk production predicted from herd history alone did not allow the
      detection of the 2007 BTV emergence in France. Further research should be
      conducted on improving the prediction of test-day milk yield and on combining it
      with other indicators based on routinely collected data.

PMID- 24433640
TI  - Intraindividual comparison of T1 relaxation times after gadobutrol and Gd-DTPA
      administration for cardiac late enhancement imaging.
AB  - PURPOSE: To evaluate T1-relaxation times of chronic myocardial infarction (CMI)
      using gadobutrol and gadopentetate dimeglumine (Gd-DTPA) over time and to
      determine the optimal imaging window for late enhancement imaging with both
      contrast agents. MATERIAL AND METHODS: Twelve patients with CMI were
      prospectively included and examined on a 1.5 T magnetic resonance (MR) system
      using relaxivity-adjusted doses of gadobutrol (0.15 mmol/kg) and Gd-DTPA (0.2
      mmol/kg) in random order. T1-relaxation times of remote myocardium (RM),
      infarcted myocardium (IM), and left ventricular cavity (LVC) were assessed from
      short-axis TI scout imaging using the Look-Locker approach and compared
      intraindividually using a Wilcoxon paired signed-rank test (alpha<0.05). RESULTS:
      Within 3 min of contrast agent administration (CA), IM showed significantly lower
      T1-relaxation times than RM with both contrast agents, indicating beginning
      cardiac late enhancement. Differences between gadobutrol and Gd-DTPA in T1
      relaxation times of IM and RM were statistically not significant through all time
      points. However, gadobutrol led to significantly higher T1-relaxation times of
      LVC than Gd-DTPA from 6 to 9 min (220 +/- 15 ms vs. 195 +/- 30 ms p<0.01)
      onwards, resulting in a significantly greater DeltaT1 of IM to LVC at 9-12 min (
      20 +/- 35 ms vs. 0 +/- 35 ms, p<0.05) and 12-15 min (-25 +/- 45 ms vs. -10 +/- 60
      ms, p<0.05). Using Gd-DTPA, comparable DeltaT1 values were reached only after 25
      35 min. CONCLUSION: This study indicates good delineation of IM to RM with both
      contrast agents as early as 3 min after administration. However, we found
      significant differences in T1 relaxation times with greater DeltaT1 IM-LVC using
      0.15 mmol/kg gadobutrol compared to 0.20 mmol/kg Gd-DTPA after 9-15 min post-CA
      suggesting earlier differentiability of IM and LVC using gadobutrol.

PMID- 24433641
TI  - Gastroenterology training in Sudan.

PMID- 24433642
TI  - Virologic and histologic characterisation of dual hepatitis B and C co-infection
      in Egyptian patients.
AB  - BACKGROUND AND STUDY AIMS: Data about dual hepatitis C (HCV) and B (HBV) co
      infection are still scarce, especially in endemic areas such as Egypt. Therefore,
      we aimed to characterise the virologic and histologic pattern of dual B/C co
      infection in a tertiary care centre in Egypt. PATIENTS AND METHODS: After
      obtaining approval from the review board, a retrospective design to evaluate the
      data registry between January 2009 and December 2012 of patients with dual HCV
      and HBV seropositivity (BC-group) at the Viral Hepatitis Unit in Ministry of
      Health and Assiut University Hospital, Egypt was conducted. Data for hepatitis B
      e antigen (HBe-Ag) and anti-HB core status, anti-hepatitis delta virus (anti
      HDV), HBV-DNA and HCV-RNA assays and liver biopsy (METAVIR scoring) results were
      collected. Two other matched groups of mono-HCV (C-group) and HBV (B-group) were
      selected as controls. All patients were naive for antiviral therapy. RESULTS: A
      total of 3300 patients were enrolled. Dual infection was observed in 25 (0.7%)
      patients (all males, mean=35.2+/-10.2years). Four patients (16%) were HBe-Ag
      positive. Six (24%) patients were HBV-DNA-negative and all were positive for HCV
      RNA. Between groups, raised alanine aminotransferase (ALT) was found in 76%,
      41.7% and 49.2% of the BC, B and C groups, respectively (p=0.023). HBV DNA
      >2000IUml(-1) was more in the B-group than in the BC-group (63.9% vs. 36%;
      p=0.042) and HCV RNA >800,000IUml(-1) was more in the BC-group than in the C
      group (28% vs. 12.3%; p=0.009). Histologically, there is no statistical
      significant difference between the three groups. CONCLUSION: Dual hepatitis B/C
      infection is not uncommon and their virologic and histologic profile is modest.
      Further evaluation with regard to treatment and long-term follow-up is warranted.

PMID- 24433643
TI  - One-stage percutaneous triple procedure for treatment of endoscopically
      unmanageable patients with malignant biliary obstruction and marked ascites.
AB  - BACKGROUND AND STUDY AIMS: To assess the feasibility, safety and efficacy of one
      stage percutaneous triple procedure including; ascites drainage, primary metallic
      biliary stenting, and tract embolisation with N-butyl 2-cyanoacrylate (NBCA), in
      treatment of patients with malignant biliary obstruction and marked ascites.
      PATIENTS AND METHODS: This study involved 25 patients with malignant biliary
      obstruction and marked ascites (age range, 46-78y; mean age+/-SD, 65y+/-5) for
      whom endoscopic treatment failed or was unsuitable. Ascites drainage,
      percutaneous primary metallic biliary stenting, and tract embolisation with
      lipiodol/NBCA mixture were performed in a one-stage procedure. The mean+/-SD
      follow up period was 26+/-2weeks. RESULTS: The technical and clinical success
      rates were 96% and 88% respectively. No procedure related deaths or major
      complications were observed. The reported minor complications included; moderate
      pain and vomiting during and after balloon dilation, postprocedural cholangitis,
      and bile leakage in 44%, 16%, and 8% of the patients respectively. Primary stent
      patency was achieved in 96%. The 30-days mortality was 8%. The stent obstruction
      occurred in 3 (13%) of the 23 patients who survived more than 30-days.
      CONCLUSIONS: Percutaneous drainage of ascites followed immediately by primary
      biliary stenting, together with tract embolisation with NBCA is technically
      feasible, safe, and effective alternative palliative treatment for endoscopically
      unmanageable patients with malignant biliary obstruction and marked ascites.

PMID- 24433644
TI  - Revising the criteria for the predictors of variceal haemorrhage outcome.
AB  - BACKGROUND AND STUDY AIMS: There are many criteria and definitions used to
      evaluate the failure to control and prevent variceal bleeding. Baveno criteria
      were developed in Baveno consensus workshops I-III. Some of these criteria are
      fairly difficult to apply and do not adequately reflect common situations that
      are observed in clinical practice. Therefore, new criteria were developed at the
      Baveno-IV workshop. In the present study, we aimed to evaluate the validity of
      Baveno II-IV criteria in the prediction of bleeding recurrence among patients
      with liver cirrhosis who presented with bleeding oesophageal varices. PATIENTS
      AND METHODS: Fifty patients with liver cirrhosis and acute variceal bleeding were
      divided into two groups according to treatment response. Group I consisted of 44
      patients for whom treatment to control bleeding was successful, and Group II
      included 6 patients for whom treatment failed. Baveno criteria were used in the
      evaluation of treatment outcome in these patients. RESULTS: The overall accuracy
      of Baveno II and III criteria was 87.3% within the first 6h and 76.5% after 6h,
      with a mean accuracy 81.9%. The overall accuracy of Baveno IV criteria in this
      study was 83%. The criterion of death was also very specific (100%), with 100%
      PPV, but its sensitivity was very low (16.7%). CONCLUSION: Baveno IV criteria are
      less complicated, much easier to apply and have nearly the same accuracy as
      Baveno II/III criteria. However, there are some criteria that need to be
      modified, such as the adjusted blood requirement index (ABR1), among others.

PMID- 24433645
TI  - A revised scope in different prognostic models in cirrhotic patients: Current and
      future perspectives, an Egyptian experience.
AB  - BACKGROUND AND STUDY AIM: The prognosis of cirrhosis is of great interest for
      liver transplantation and new therapies of related complications. Traditional
      prognostic models such as Child-Pugh (CP) and Model for End-stage Liver Disease
      (MELD) were developed to predict mortality in decompensated cirrhosis, but lack
      parameter(s) related to complications. Recently, new models such as creatinine
      modified Child-Turcotte-Pugh (CrCTP) and sodium-based MELD variants were
      developed to improve prognostic accuracy and enhance outcome predictive
      capability. Our aim was to investigate the prognostic ability of these models and
      their relation to complications among Egyptian cirrhotic patients to determine
      the best one and to assess adding new variables to improve the prognostic ability
      of that model. PATIENTS AND METHODS: A total of 1000 cirrhotic patients were
      enrolled in a retrospective study; traditional and new prognostic models such as
      CP, MELD, CrCTP, integrated MELD (iMELD), MELD plus sodium (MELD-Na, MELDNa) and
      MELD:sodium ratio (MESO) were calculated. The predictive abilities of prognostic
      models were compared using the area under receiver operating characteristic curve
      (AUC) and 1-year survival rates were evaluated by Kaplan-Meier survival analysis.
      An index of cirrhosis-related complications was added to reveal the best
      prognostic model. RESULTS: Using AUC, MELD and its sodium variants was
      significantly better than CP and CrCTP scores in predicting risk of 1-year
      mortality, where MELD-sodium (MELD-Na) had the highest AUC (0.743). Adding an
      index of cirrhosis-related complications (C) to MELD-Na creating a new scoring
      system (MELD-Na-C) improved its prognostic accuracy (AUC 0.753). Kaplan-Meier
      survival curves predicted increased mortality with higher prognostic scores.
      CONCLUSIONS: All prognostic models were good predictors of 1-year mortality in
      patients with decompensated cirrhosis; however, MELD-Na was the best for outcome
      prediction. MELD-Na-C was a new model enhancing the predictive accuracy in
      assessing cirrhotic patients with related complications.

PMID- 24433646
TI  - Zero inflated statistical count models for analysing the costs imposed by GERD
      and dyspepsia.
AB  - BACKGROUND AND STUDY AIMS: Recent studies have shown that the high prevalence and
      the various clinical presentations of gastro-oesophageal reflux disease (GERD)
      and dyspepsia impose an enormous economic burden on society. Economic cost data
      have unique characteristics: they are counts, and they have zero inflation.
      Therefore, these data require special models. Poisson regression (PR), negative
      binomial regression (NB), zero inflated Poisson (ZIP) and zero inflated negative
      binomial (ZINB) regression are the models used for analysing cost data in this
      paper. PATIENTS AND METHODS: In this study, a cross-sectional household survey
      was distributed to a random sample of individuals between May 2006 and December
      2007 in the Tehran province of Iran to determine the prevalence of
      gastrointestinal symptoms and disorders and their related factors. The cost
      associated with each item was calculated. PR, NB, ZIP and ZINB models were used
      to analyse the data. The likelihood ratio test and the Voung test were used to
      conduct pairwise comparisons of the models. The log likelihood, the Akaike
      information criterion (AIC) and the Bayesian information criterion (BIC) were
      used to compare the performances of the models. RESULTS: According to the
      likelihood ratio test and the Voung test and all three criteria used to compare
      the performance of the models, ZINB regression was identified as the best model
      for analysing the cost data. Sex, age, smoking status, BMI, insurance status and
      education were significant predictors. CONCLUSION: Because the NB model
      demonstrated a better fit than the PR and ZIP models, over-dispersion was clearly
      only due to unobserved heterogeneity. In contrast, according to the likelihood
      ratio test, the ZINB model was more appropriate than the ZIP model. The ZINB
      model for the cost data was more appropriate than the other models.

PMID- 24433647
TI  - Epidemiology of Helicobacter pylori infection among Iranian children.
AB  - BACKGROUND AND STUDY AIMS: Infection with Helicobacter pylori (HP) either in
      children or in adults is a risk factor for gastric cancer. The Golestan province
      located in northeast Iran has been known to be a high-risk area for oesophageal
      and gastric cancers. This study was conducted to assess the epidemiology of this
      infection in the children of Golestan. PATIENTS AND METHODS: This study was
      carried out in 2009 on healthy children (1-15years) of the Golestan province.
      Serum immunoglobulin G (Ig G) antibody against HP was tested in these children
      and positive samples were tested for anti-cytotoxin-associated antigen A (anti
      CagA) antibody. To assess the relationship between HP infection and the risk of
      gastric cancer, the Golestan province was divided into high- and low-risk areas
      based on the incidence rate of gastric cancer. The chi-squared test was used to
      assess the relationship between variables. RESULTS: Totally, 194 subjects were
      recruited. The prevalence of HP infection in our area was 50.5%. The prevalence
      of HP infection was significantly higher in the high-risk than in the low-risk
      area for stomach cancer (p=0.004). The seropositivities of HP (p=0.03) and CagA
      (p=0.04) were significantly lower in children <5years than in others. CONCLUSION:
      Our results showed a high prevalence of HP infection in children of the Golestan
      province of Iran. We also found a significant positive relationship between
      childhood HP infection and the risk of gastric cancer. Hence, childhood HP
      infection may be considered a possible determinant of gastric cancer in this high
      risk area. Implementation of preventive programmes may help to reduce the burden
      of childhood HP infection and, consequently, gastric cancer in this area.

PMID- 24433648
TI  - Fibropolycystic disease of the liver and kidney in Oman.
AB  - BACKGROUND AND STUDY AIMS: Fibropolycystic disease of liver and kidney (FPCDLK)
      is an uncommon group of conditions inherited in an autosomal fashion. The group
      encompasses autosomal dominant polycystic disease of the kidney (ADPDK),
      autosomal recessive polycystic disease of the kidney (ARPDK), congenital hepatic
      fibrosis (CHF) and Caroli's disease (CD). There are limited data of this disease
      in the world. We report our experience in the Royal Hospital (RH) in Oman and
      data regarding long-term follow-up. The aim of the study was to document the
      frequency of encounter, clinical presentation and outcome of FPCDLK in Division
      of Child Health in RH, Muscat. PATIENTS AND METHODS: Charts of patients diagnosed
      with ARPDK, ADPDK, CHF and CD were reviewed from the period of 16 February 2006
      till 31 December 2011. Parameters including anthropometry, liver function tests,
      renal function tests, presence of oesophageal varices, hypersplenism, renal or
      liver transplantation and performance of porto-systemic shunt surgeries were all
      investigated. RESULTS: A total of 33 patients were identified, including 19 males
      and 14 females. The frequency of encounter of FPCDLK in RH was 1.5/1,000,000
      population. The mean age of patients was 7.4years. The mean age at diagnosis was
      27months. The mean duration of follow-up was 5.5years. A total of 31% of patients
      had an incidental finding of hepatomegaly, and 25% were detected by antenatal
      screening. Three children presented with renal failure, and 13 children in total
      had renal function abnormalities by the end of the study period. One child
      presented with haematemesis at the age of 1year. Two children underwent renal
      transplant and one child required splenectomy with a splenorenal shunt. A total
      of 54% had endoscopic variceal screen and two required banding on first
      endoscopy. The demise of one patient was observed during the study. CONCLUSION:
      FPCDLK is uncommon in Oman but carries major mortality and morbidity for the
      patient and family. The gene is present in the Gulf countries. Management is
      mainly through portal hypertension and renal supportive care until definitive
      dual organ transplant. This disease needs to be further investigated in the Arab
      world.

PMID- 24433649
TI  - Ischaemic hepatitis precipitated by recurrent episodes of atrial fibrillation.
AB  - We report a case of ischaemic hepatitis associated with recurrent fast atrial
      fibrillation (AF) episodes in a 59-year-old male who presented with shortness of
      breath, nausea and vomiting. The patient had a history of ischaemic
      cardiomyopathy. An emergency electrocardiogram showed fast AF with a ventricular
      rate of 190 min(-1). The aspartate aminotransferase (AST) level was 2222Ul(-1),
      alanine aminotransferase (ALT) was 1255Ul(-1), lactate dehydrogenase (LDH) was
      1842Ul(-1) and serum creatinine was 150 MUmoll(-1). An ultrasound of the abdomen
      showed an enlarged liver with hypoechoic lesions. The patient received digoxin.
      In the next few days, while liver enzymes and serum creatinine started to return
      to normal levels, the patient had two attacks of fast AF, each associated with
      elevated liver enzymes and a concomitant rise in serum creatinine. The patient
      was transferred to the intensive care unit to improve control of his AF, after
      which his liver enzymes and renal function gradually returned to normal.

PMID- 24433650
TI  - Anticoagulant-induced intramural duodenal haematoma presenting with upper
      gastrointestinal haemorrhage.
AB  - Warfarin is an anticoagulant agent known to have a common complication, bleeding.
      Intramural intestinal haematoma is an uncommon incidence of warfarin-induced
      haemorrhage. Abdominal pain is its most frequent symptom and presentation with
      upper-gastrointestinal haemorrhage is rarely seen. Here, we present a 67-year-old
      male who was admitted to the hospital with active upper-gastrointestinal
      haemorrhage. In this case, the cause of bleeding has been attributed to duodenal
      intramural haematoma due to warfarin overuse. 

PMID- 24433651
TI  - Plummer Vinson syndrome association with coeliac disease.

PMID- 24433652
TI  - Multidetector computed tomography in the diagnosis of insulinoma.

PMID- 24433654
TI  - ART and the art of medicine.

PMID- 24433655
TI  - Assisted reproduction for postmenopausal women.

PMID- 24433656
TI  - Physician responsibility when a surrogate mother breaks her contract.

PMID- 24433657
TI  - Are IVF risk-sharing programs ethical?

PMID- 24433658
TI  - Shared decision making about IVF for savior siblings.

PMID- 24433659
TI  - Health and development of children conceived through assisted reproduction.

PMID- 24433660
TI  - Expanded genetic testing in assisted reproductive technology: lessons learned
      from prenatal testing.

PMID- 24433661
TI  - Physician duties in the face of deceitful gamete donors, disobedient surrogate
      mothers, and divorcing parents.

PMID- 24433662
TI  - Fully informed consent for prospective egg donors.

PMID- 24433663
TI  - Egg-donor price fixing and Kamakahi v. American Society for Reproductive
      Medicine.

PMID- 24433664
TI  - Who pays? Mandated insurance coverage for assisted reproductive technology.

PMID- 24433665
TI  - The relative effectiveness of five antiepileptic drugs in treatment of
      benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of
      published studies.
AB  - PURPOSE: Systematic evaluation of published evidence-base of the efficacy of five
      antiepileptic drugs - lacosamide, levetiracetam, valproate, phenytoin and
      phenobarbital - in convulsive benzodiazepine-resistant status epilepticus.
      METHODS: Data sources included electronic databases, personal communication, and
      back tracing of references in pertinent studies. These were prospective and
      retrospective human studies presenting original data for participants with
      convulsive benzodiazepine-resistant status epilepticus. Interventions were
      intravenous lacosamide, levetiracetam, phenobarbital, phenytoin and valproate.
      Outcome measured is clinically detectable cessation of seizure activity. Level-of
      evidence was assessed according to Oxford Centre of Evidence-Based Medicine and
      The Cochrane Collaboration's Tool for Assessment of Risk. Twenty seven studies
      (798 cases of convulsive status epilepticus) were identified and 22 included in a
      meta-analysis. Random-effects analysis of dichotomous outcome of a single group
      estimate (proportion), with inverse variance weighting, was implemented. Several
      sources of clinical and methodological heterogeneity were identified. RESULTS:
      Efficacy of levetiracetam was 68.5% (95% CI: 56.2-78.7%), phenobarbital 73.6%
      (95% CI: 58.3-84.8%), phenytoin 50.2% (95% CI: 34.2-66.1%) and valproate 75.7%
      (95% CI: 63.7-84.8%). Lacosamide studies were excluded from the meta-analysis due
      to insufficient data. CONCLUSION: Valproate, levetiracetam and phenobarbital can
      all be used as first line therapy in benzodiazepine-resistant status epilepticus.
      The evidence does not support the first-line use of phenytoin. There is not
      enough evidence to support the routine use of lacosamide. Randomized controlled
      trials are urgently needed.

PMID- 24433666
TI  - Advances made in traumatology: the Italian perspective.

PMID- 24433667
TI  - Dependence of elbow joint stiffness measurements on speed, angle, and muscle
      contraction level.
AB  - Elbow joint stiffness is critical to positioning the hand. Abnormal elbow joint
      stiffness may affect a person's ability to participate in activities of daily
      living. In this work, elbow joint stiffness was measured in ten healthy young
      adults with a device adapted from one previously used to measure stiffness in
      other joints. Measurements of elbow stiffness involved applying a constant
      velocity rotational movement to the elbow and measuring the resultant
      displacement, torque, and acceleration. Elbow stiffness was then computed using a
      previously-established model for joint stiffness. Measurements were made at two
      unique elbow joint angles, two speeds, and two forearm muscle contraction levels.
      The results indicate that the elbow joint stiffness is significantly affected by
      both rotational speed and forearm muscle contraction level. 

PMID- 24433668
TI  - Non-invasive in vivo measurement of the shear modulus of human vocal fold tissue.
AB  - Voice is the essential part of singing and speech communication. Voice disorders
      significantly affect the quality of life. The viscoelastic mechanical properties
      of the vocal fold mucosa determine the characteristics of the vocal folds
      oscillations, and thereby voice quality. In the present study, a non-invasive
      method was developed to determine the shear modulus of human vocal fold tissue in
      vivo via measurements of the mucosal wave propagation speed during phonation.
      Images of four human subjects' vocal folds were captured using high speed digital
      imaging (HSDI) and magnetic resonance imaging (MRI) for different phonation
      pitches, specifically fundamental frequencies between 110 and 440 Hz. The MRI
      images were used to obtain the morphometric dimensions of each subject's vocal
      folds in order to determine the pixel size in the high-speed images. The mucosal
      wave propagation speed was determined for each subject and at each pitch value
      using an automated image processing algorithm. The transverse shear modulus of
      the vocal fold mucosa was then calculated from a surface (Rayleigh) wave
      propagation dispersion equation using the measured wave speeds. It was found that
      the mucosal wave propagation speed and therefore the shear modulus of the vocal
      fold tissue were generally greater at higher pitches. The results were in good
      agreement with those from other studies obtained via in vitro measurements,
      thereby supporting the validity of the proposed measurement method. This method
      offers the potential for in vivo clinical assessments of vocal folds
      viscoelasticity from HSDI.

PMID- 24433669
TI  - Assessment of standing balance deficits in people who have undergone anterior
      cruciate ligament reconstruction using traditional and modern analysis methods.
AB  - Modern methods of assessing standing balance such as wavelet and entropy analysis
      could provide insight into postural control mechanisms in clinical populations.
      The aim of this study was to examine what effect anterior cruciate ligament
      reconstruction (ACLR) has on traditional and modern measures of balance. Ninety
      subjects, 45 who had undergone ACLR and 45 matched controls, performed single leg
      static standing balance tests on their surgical or matched limb on a Nintendo Wii
      Balance Board. Data were analysed in the anterior-posterior axis of movement,
      which is known to be affected by ACLR. The traditional measures of path velocity,
      amplitude and standard deviation were calculated in this plane. Additionally,
      sample entropy and discrete wavelet transform derived assessment of path velocity
      in four distinct frequency bands related to (1) spinal reflexive loops and muscle
      activity, (2) cerebellar, (3) vestibular, and (4) visual mechanisms of postural
      control were derived. The ACLR group had significantly increased values in all
      traditional measures and all four frequency bands. No significant difference was
      observed for sample entropy. This indicated that whilst postural sway was
      amplified in the ACLR group, the overall mechanism used by the patient group to
      maintain balance was similar to that of the control group. In conclusion, modern
      methods of signal analysis may provide additional insight into standing balance
      mechanisms in clinical populations. Future research is required to determine if
      these results provide important and unique information which is of benefit to
      clinicians. 

PMID- 24433670
TI  - An ultrasound based non-invasive method for the measurement of intrinsic foot
      kinematics during gait.
AB  - Soft tissue artefact (STA) and marker placement variability are sources of error
      when measuring the intrinsic kinematics of the foot. This study aims to
      demonstrate a non-invasive, combined ultrasound and motion capture (US/MC)
      technique to directly measure foot skeletal motion. The novel approach is
      compared to a standard motion capture protocol. Fourteen participants underwent
      instrumented barefoot analysis of foot motion during gait. Markers were attached
      to foot allowing medial longitudinal arch angle and navicular height to be
      determined. For the US/MC technique, the navicular marker was replaced by an
      ultrasound transducer which was secured to the foot allowing the skeletal
      landmark to be imaged. Ultrasound cineloops showing the location of the navicular
      tuberosity during the walking trials were synchronised with motion capture
      measurements and markers mounted on the probe allowed the true position of the
      bony landmark to be determined throughout stance phase. Two discrete variables,
      minimum navicular height and maximum MLA angle, were compared between the
      standard and US/MC protocols. Significant differences between minimum navicular
      height (P=0.004, 95% CI (1.57, 6.54)) and maximum medial longitudinal arch angle
      (P=0.0034, 95% CI (13.8, 3.4)) were found between the measurement methods. The
      individual effects of STA and marker placement error were also assessed. US/MC is
      a non-invasive technique which may help to provide more accurate measurements of
      intrinsic foot kinematics. 

PMID- 24433671
TI  - Age-related changes in mouse bone permeability.
AB  - The determination of lacunar-canalicular permeability is essential for
      understanding local fluid flow in bone, which may indicate how bone senses
      changes in the mechanical environment to regulate mechano-adaptation. The
      estimates of lacunar-canalicular permeability found in the literature vary by up
      to eight orders of magnitude, and age-related permeability changes have not been
      measured in non-osteonal mouse bone. The objective of this study is to use a
      poroelastic approach based on nanoindentation data to characterize lacunar
      canalicular permeability in murine bone as a function of age. Nine wild type
      C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from
      each age group were embedded in epoxy resin, cut in half and indented in the
      longitudinal direction in the mid-cortex using two spherical fluid indenter tips
      (R=238 MUm and 500 MUm). Results suggest that the lacunar-canalicular intrinsic
      permeability of mouse bone decreases from 2 to 7 months, with no significant
      changes from 7 to 12 months. The large indenter tip imposed larger contact sizes
      and sampled larger ranges of permeabilities, particularly for the old bone. This
      age-related difference in the distribution was not seen for indents with the
      smaller radius tip. We conclude that the small tip effectively measured lacunar
      canalicular permeability, while larger tip indents were influenced by vascular
      permeability. Exploring the age-related changes in permeability of bone measured
      by nanoindentation will lead to a better understanding of the role of fluid flow
      in mechano-transduction. This understanding may help indicate alterations in bone
      adaptation and remodeling.

PMID- 24433673
TI  - Stipe wall extension of Flammulina velutipes could be induced by an expansin-like
      protein from Helix aspersa.
AB  - Expansin proteins extend plant cell walls by a hydrolysis-free process that
      disrupts hydrogen bonding between cell wall polysaccharides. However, it is
      unknown if this mechanism is operative in mushrooms. Herein we report that the
      native wall extension activity was located exclusively in the 10 mm apical region
      of 30 mm Flammulina velutipes stipes. The elongation growth was restricted also
      to the 9 mm apical region of the stipes where the elongation growth of the 1st
      millimetre was 40-fold greater than that of the 5th millimetre. Therefore, the
      wall extension activity represents elongation growth of the stipe. The low
      concentration of expansin-like protein in F. velutipes stipes prevented its
      isolation. However, we purified an expansin-like protein from snail stomach juice
      which reconstituted heat-inactivated stipe wall extension without hydrolytic
      activity. So the previous hypotheses that stipe wall extension was resulted from
      hydrolysis of wall polymers by enzymes or disruption of hydrogen bonding of wall
      polymers exclusively by turgor pressure are challenged. We suggest that stipe
      wall extension may be mediated by endogenous expansin-like proteins that
      facilitate cell wall polymer slippage by disrupting noncovalent bonding between
      glucan chains or chitin chains. 

PMID- 24433672
TI  - Intraspecific variation in Burkholderia caledonica: Europe vs. Africa and soil
      vs. endophytic isolates.
AB  - The best-known interaction between bacteria and plants is the Rhizobium-legume
      symbiosis, but other bacteria-plant interactions exist, such as between
      Burkholderia and Rubiaceae (coffee family). A number of bacterial endophytes in
      Rubiaceae are closely related to the soil bacterium Burkholderia caledonica. This
      intriguing observation is explored by investigating isolates from different
      geographic regions (Western Europe vs. sub-Saharan Africa) and from different
      niches (free-living bacteria in soil vs. endophytic bacteria in host plants). The
      multilocus sequence analysis shows five clades, of which clade 1 with two basal
      isolates deviates from the rest and is therefore not considered further. All
      other isolates belong to the species B. caledonica, but two genetically different
      groups are identified. Group A holds only European isolates and group B holds
      isolates from Africa, with the exception of one European isolate. Although the
      European and African isolates are considered one species, some degree of genetic
      differentiation is evident. Endophytic isolates of B. caledonica are found in
      certain members of African Rubiaceae, but only in group B. Within this group, the
      endophytes cannot be distinguished from the soil isolates, which indicates a
      possible exchange of bacteria between soil and host plant. 

PMID- 24433674
TI  - The Paxillus involutus (Boletales, Paxillaceae) complex in Europe: genetic
      diversity and morphological description of the new species Paxillus cuprinus,
      typification of P. involutus s.s., and synthesis of species boundaries.
AB  - Paxillus involutus is a model species for ecological or physiological studies of
      ectomycorrhizal agaricomycetes. Three to six groups or species linked to it have
      been ecologically and morphologically distinguished. Phylogenetic studies have
      revealed the existence of four species in Europe: Paxillus ammoniavirescens,
      Paxillus obscurisporus, P. involutus, and a fourth as yet not described species.
      We studied 47 collections from 24 French and Italian locations, supplemented with
      GenBank data, in order to genetically and taxonomically delineate these species.
      Phylogenetic analyses of three nuclear DNA regions (rDNA internal transcribed
      spacer (ITS), tef1-alpha, and gpd) confirmed the four European species.
      Morphology, culture, and ecology features allowed us to delineate species
      boundaries and to describe the fourth species we named Paxillus cuprinus since it
      turns coppery with age. As there is no existing original herbarium specimen for
      P. involutus, one of our collections was chosen as the epitype. The low genetic
      diversity found in P. cuprinus correlates with stable morphological traits
      (basidiome colour, ovoid-amygdaliform spores with an apical constriction) and
      with ecological preferences (association with Betulaceae in open and temperate
      areas). In contrast, P. ammoniavirescens is characterized by a high genetic
      diversity and a high variation of its morphological and ecological features. 

PMID- 24433676
TI  - Nikkomycin Z is an effective inhibitor of the chytrid fungus linked to global
      amphibian declines.
AB  - Fungal infections in humans, wildlife, and plants are a growing concern because
      of their devastating effects on human and ecosystem health. In recent years,
      populations of many amphibian species have declined, and some have become extinct
      due to chytridiomycosis caused by the fungal pathogen Batrachochytrium
      dendrobatidis. For some endangered amphibian species, captive colonies are the
      best intermediate solution towards eventual reintroduction, and effective
      antifungal treatments are needed to cure chytridiomycosis and limit the spread of
      this pathogen in such survival assurance colonies. Currently, the best accepted
      treatment for infected amphibians is itraconazole, but its toxic side effects
      reduce its usefulness for many species. Safer antifungal treatments are needed
      for disease control. Here, we show that nikkomycin Z, a chitin synthase
      inhibitor, dramatically alters the cell wall stability of B. dendrobatidis cells
      and completely inhibits growth of B. dendrobatidis at 250 MUM. Low doses of
      nikkomycin Z enhanced the effectiveness of natural antimicrobial skin peptide
      mixtures tested in vitro. These studies suggest that nikkomycin Z would be an
      effective treatment to significantly reduce the fungal burden in frogs infected
      by B. dendrobatidis. 

PMID- 24433675
TI  - Diversity of the cassiicolin gene in Corynespora cassiicola and relation with the
      pathogenicity in Hevea brasiliensis.
AB  - Corynespora cassiicola is an important plant pathogenic Ascomycete causing the
      damaging Corynespora Leaf Fall (CLF) disease in rubber tree (Hevea brasiliensis).
      A small secreted glycoprotein named cassiicolin was previously described as an
      important effector of C. cassiicola. In this study, the diversity of the
      cassiicolin-encoding gene was analysed in C. cassiicola isolates sampled from
      various hosts and geographical origins. A cassiicolin gene was detected in 47 %
      of the isolates, encoding up to six distinct protein isoforms. In three isolates,
      two gene variants encoding cassiicolin isoforms Cas2 and Cas6 were found in the
      same isolate. A phylogenetic tree based on four combined loci and elucidating the
      diversity of the whole collection was strongly structured by the toxin class, as
      defined by the cassiicolin isoform. The isolates carrying the Cas1 gene (toxin
      class Cas1), all grouped in the same highly supported clade, were found the most
      aggressive on two rubber tree cultivars. Some isolates in which no Cas gene was
      detected could nevertheless generate moderate symptoms, suggesting the existence
      of other yet uncharacterized effectors. This study provides a useful base for
      future studies of C. cassiicola population biology and epidemiological surveys in
      various host plants. 

PMID- 24433677
TI  - Taxonomic and phenotypic characterization of yeasts isolated from worldwide cold
      rock-associated habitats.
AB  - Yeast strains isolated from rock samples collected from worldwide cold regions
      were identified by sequence analysis of the D1/D2 domains of the 26S rDNA gene
      and the ITS region followed by molecular phylogeny. Over 77% of yeasts isolates
      were Basidiomycota. Cryptococcus (orders Filobasidiales and Tremellales) and
      Rhodotorula (order Cystobasidiales) were the most frequent genera. About 40% of
      yeast isolates belonged to undescribed species. Almost all isolates were
      psychrotolerant. Urease and esterase were the most widely extracellular enzymatic
      activity at 4  degrees C and 20  degrees C. None of the strains exhibited
      extracellular protease, DNAse, cellulase, chitinase, and laccase activity. The
      taxonomic and ecological significance of yeasts associated to worldwide cold
      rocky habitats is discussed.

PMID- 24433678
TI  - Two novel species representing a new clade and cluster of Phytophthora.
AB  - Phytophthora stricta sp. nov. and Phytophthora macilentosa sp. nov. are described
      based on morphological, physiological and molecular characters in this study.
      Phytophthora stricta represents a previously unknown clade in the rRNA internal
      transcribed spacer (ITS)-based phylogeny. Phytophthora macilentosa, along with
      nine other species, consistently forms a high temperature-tolerant cluster within
      ITS clade 9. These observations are supported by the sequence analysis of the
      mitochondrial cytochrome c oxidase 1 gene. Both species are heterothallic and all
      examined isolates are A1 mating type. Phytophthora stricta produces nonpapillate
      and slightly caducous sporangia. This species is named after its characteristic
      constrictions on sporangiophores. Phytophthora macilentosa produces nonpapillate
      and noncaducous sporangia, which are mostly elongated obpyriform with a high
      length to breadth ratio. Both species were recovered from irrigation water of an
      ornamental plant nursery in Mississippi, USA and P. stricta was also recovered
      from stream water in Virginia, USA. 

PMID- 24433679
TI  - The phytoalexin camalexin induces fundamental changes in the proteome of
      Alternaria brassicicola different from those caused by brassinin.
AB  - Camalexin is the major phytoalexin produced by Alternaria thaliana, but is absent
      in Brassica species that usually produce phytoalexin blends containing brassinin
      and derivatives. The protein profiles of A. brassicicola treated with camalexin
      were evaluated using proteomics and metabolic analyses and compared with those
      treated with brassinin. Conidial germination and mycelial growth of A.
      brassicicola in liquid media amended with camalexin and brassinin showed that
      fungal growth was substantially slower in presence of camalexin than brassinin;
      chemical analyses revealed that A. brassicicola detoxified camalexin at much
      slower rate than brassinin. Two-dimensional gel electrophoresis (2-DE) followed
      by tryptic digestion and capillary liquid chromatography-mass spectrometric
      analyses identified 158 different proteins, of which 45 were up-regulated and 113
      were down-regulated relative to controls. Venn diagram analyses of differentially
      expressed proteins in cultures of A. brassicicola incubated with camalexin and
      brassinin indicated clear differences in the effect of each phytoalexin, with
      camalexin causing down-regulation of a larger number of proteins than brassinin.
      Overall, results of this work suggest that each phytoalexin has several different
      targets in the cells of A. brassicicola, and that camalexin appears to have
      greater potential to protect cultivated Brassica species against A. brassicicola
      than brassinin. 

PMID- 24433680
TI  - Scedosporium prolificans immunomes against human salivary immunoglobulin A.
AB  - The filamentous fungus Scedosporium prolificans is an emerging multidrug
      resistant pathogen related to serious infections mainly affecting
      immunocompromised individuals. Considering that it is frequently isolated from
      anthropic environments and penetrates mainly through the airways, the human
      mucosal immune system may play an important protective role against S.
      prolificans. To advance in the search for biomarkers and targets both for
      diagnosis and treatment, we analysed the S. prolificans immunomes recognized by
      human salivary Immunoglobulin A. Using indirect immunofluorescence, it was
      observed that conidia were strongly recognized, while hyphae were not. By 2-D
      immunoblotting and peptide mass fingerprinting, 25 immunodominant antigens in
      conidia and 30 in hyphae were identified. These included catalase, putative
      glyceronetransferase, translation elongation factor-1alpha, serine/threonine
      protein kinase, putative superoxide dismutase, putative mitochondrial cyclophilin
      1 and peptidyl-prolyl cis-trans isomerase in conidiospores, and putative Hsp60,
      ATP synthase beta chain, 40S ribosomal protein S0, citrate synthase and putative
      ATP synthase in hyphae. The functional study showed that metabolism - and protein
      fate - related enzymes were the most abundant antigens in conidia, whereas
      metabolism - , translation - , or energy production - related enzymes were in
      hyphae. The immunogenic proteins identified are proposed as candidates for the
      development of novel diagnostic tools or therapeutic strategies. 

PMID- 24433681
TI  - HPV self-testing and cervical cancer screening coverage.

PMID- 24433682
TI  - Preferences for cancer investigation: a vignette-based study of primary-care
      attendees.
AB  - BACKGROUND: The UK lags behind many European countries in terms of cancer
      survival. Initiatives to address this disparity have focused on barriers to
      presentation, symptom recognition, and referral for specialist investigation.
      Selection of patients for further investigation has come under particular
      scrutiny, although preferences for referral thresholds in the UK population have
      not been studied. We investigated preferences for diagnostic testing for
      colorectal, lung, and pancreatic cancers in primary-care attendees. METHODS: In a
      vignette-based study, researchers recruited individuals aged at least 40 years
      attending 26 general practices in three areas of England between Dec 6, 2011, and
      Aug 1, 2012. Participants completed up to three of 12 vignettes (four for each of
      lung, pancreatic, and colorectal cancers), which were randomly assigned. The
      vignettes outlined a set of symptoms, the risk that these symptoms might indicate
      cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment,
      possible alternative diagnoses, and prognosis if cancer were identified.
      Participants were asked whether they would opt for diagnostic testing on the
      basis of the information in the vignette. FINDINGS: 3469 participants completed
      6930 vignettes. 3052 individuals (88%) opted for investigation in their first
      vignette. We recorded no strong evidence that participants were more likely to
      opt for investigation with a 1% increase in risk of cancer (odds ratio [OR] 1.02,
      95% CI 0.99-1.06; p=0.189), although the association between risk and opting for
      investigation was strong when colorectal cancer was analysed alone (1.08, 1.03
      1.13; p=0.0001). In multivariable analysis, age had an effect in all three cancer
      models: participants aged 60-69 years were significantly more likely to opt for
      investigation than were those aged 40-59 years, and those aged 70 years or older
      were less likely. Other variables associated with increased likelihood of opting
      for investigation were shorter travel times to testing centre (colorectal and
      lung cancers), a family history of cancer (colorectal and lung cancers), and
      higher household income (colorectal and pancreatic cancers). INTERPRETATION:
      Participants in our sample expressed a clear preference for diagnostic testing at
      all risk levels, and individuals want to be tested at risk levels well below
      those stipulated by UK guidelines. This willingness should be considered during
      design of cancer pathways, particularly in primary care. The public engagement
      with our study should encourage general practitioners to involve patients in
      referral decision making. FUNDING: The National Institute for Health Research
      Programme Grants for Applied Research programme.

PMID- 24433683
TI  - The importance of primary care for cancer diagnoses.

PMID- 24433685
TI  - [Emphasizing the clinical investigation of dry eye].
AB  - In the past twenty years, with the rapid development of dry eye research in
      China, significant progresses have been achieved and there has been a remarkable
      improvement in diagnostic rate and clinical outcomes. Publication and
      popularization of the clinical diagnosis and treatment recommendations for dry
      eye from consensus of expert advice provides criteria for clinical work of dry
      eye. There has still been a significant gap between our research and world's
      advanced level in dry eye, therefore clinical investigations of high level will
      be intensively promoted to reveal the epidemiologic and clinical characteristics
      of dry eye populations in China, and establish the diagnostic criteria for
      Chinese patients, develop the clinical research on dry eye drugs and home-made
      clinical devices. Based on evidence-based research evidences, criteria for
      diagnosis and treatment of dry eye will be established and the clinical
      investigation of dry eye will be developed to reach the world's advanced level. 

PMID- 24433684
TI  - Accuracy of human papillomavirus testing on self-collected versus clinician
      collected samples: a meta-analysis.
AB  - BACKGROUND: Screening for human papillomavirus (HPV) infection is more effective
      in reducing the incidence of cervical cancer than screening using Pap smears.
      Moreover, HPV testing can be done on a vaginal sample self-taken by a woman,
      which offers an opportunity to improve screening coverage. However, the clinical
      accuracy of HPV testing on self-samples is not well-known. We assessed whether
      HPV testing on self-collected samples is equivalent to HPV testing on samples
      collected by clinicians. METHODS: We identified relevant studies through a search
      of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they
      fulfilled all of the following selection criteria: a cervical cell sample was
      self-collected by a woman followed by a sample taken by a clinician; a high-risk
      HPV test was done on the self-sample (index test) and HPV-testing or cytological
      interpretation was done on the specimen collected by the clinician (comparator
      tests); and the presence or absence of cervical intraepithelial neoplasia grade 2
      (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in
      women with one or more positive tests. The absolute accuracy for finding CIN2 or
      worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well
      as the relative accuracy of the index versus the comparator tests were pooled
      using bivariate normal models and random effect models. FINDINGS: We included
      data from 36 studies, which altogether enrolled 154 556 women. The absolute
      accuracy varied by clinical setting. In the context of screening, HPV testing on
      self-samples detected, on average, 76% (95% CI 69-82) of CIN2 or worse and 84%
      (72-92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or
      worse was 86% (83-89) and 87% (84-90) to exclude CIN3 or worse. The variation of
      the relative accuracy of HPV testing on self-samples compared with tests on
      clinician-taken samples was low across settings, enabling pooling of the relative
      accuracy over all studies. The pooled sensitivity of HPV testing on self-samples
      was lower than HPV testing on a clinician-taken sample (ratio 0.88 [95% CI 0.85
      0.91] for CIN2 or worse and 0.89 [0.83-0.96] for CIN3 or worse). Also specificity
      was lower in self-samples versus clinician-taken samples (ratio 0.96 [0.95-0.97]
      for CIN2 or worse and 0.96 [0.93-0.99] for CIN3 or worse). HPV testing with
      signal-based assays on self-samples was less sensitive and specific than testing
      on clinician-based samples. By contrast, some PCR-based HPV tests generally
      showed similar sensitivity on both self-samples and clinician-based samples.
      INTERPRETATION: In screening programmes using signal-based assays, sampling by a
      clinician should be recommended. However, HPV testing on a self-sample can be
      suggested as an additional strategy to reach women not participating in the
      regular screening programme. Some PCR-based HPV tests could be considered for
      routine screening after careful piloting assessing feasibility, logistics,
      population compliance, and costs. FUNDING: The 7th Framework Programme of the
      European Commission, the Belgian Foundation against Cancer, the International
      Agency for Research on Cancer, and the German Guideline Program in Oncology.

PMID- 24433686
TI  - [Mitomycin C related complications shouldn't be neglected in the pterygium
      surgery].
AB  - Mitomycin C (MMC), as it could reduce tissue adhesions and scar formation, has
      been widely adopted in pterygium surgery to lower the recurrence rate.Upon a
      certain therapeutic effect obtained, a variety of ocular complications was
      combined and always occupies a quite long time after MMC application.once
      occurred, it was tough to cure. Compared to autologous limbal-conjunctival
      grafts, MMC has no apparent advantage to reduce reoccurrence of pterygium.
      Therefore, it is advised to abandon the use of MMC in pterygium surgery. 

PMID- 24433687
TI  - [Glaucoma and Moscow Eye Microsurgery complex (Moroz) keratoprosthesis].
AB  - OBJECTIVE: To investigate the relationship between glaucoma and Moscow Eye
      Microsurgery Complex (Moroz) keratoprosthesis. METHODS: Analysis and
      retrospective review of consecutive clinical case series. A total of 90 patients
      had a Moroz keratoprosthesis implantation between Apr, 2000 and Jun, 2011 at our
      hospital.Fifteen eyes of 15 patients were included in this research. Twelve eyes
      were identified glaucoma before Moroz keratoprosthesis surgery, and 3 eyes
      developed glaucoma afterward.Intraocular pressure (IOP), best-corrected visual
      acuity (BCVA), and treatment of glaucoma were recorded at 1 to 3 months after the
      Moroz keratoprosthesis implantation. RESULTS: Moroz keratoprosthesis surgery
      improved vision dramatically in the majority of patients in our study. The most
      common preoperative corneal diagnosis was alkali burn (8 eyes, 53.3%), which
      maybe the risk factor of secondary glaucoma after keratoprosthesis surgery.Five
      of these 15 patients received cyclocryotherapy after the surgery to control
      elevated IOP. BCVA decreased from 0.8 to 0.2, 0.25 to light perception, 0.3 to
      0.1, 0.2 to hand movement, and 0.25 to counting fingers, respectively.
      CONCLUSIONS: Moroz keratoprosthesis caused glaucoma in only a small number of
      patients.Visual field, optic nerve appearance and IOP were the main diagnostic
      modalities after Moroz keratoprosthesis implantation.

PMID- 24433688
TI  - [Study on the clinical manifestation of 438 cases with blepharitis].
AB  - OBJECTIVE: To summarize the clinical characteristics and the therapy effect of
      blepharitis patients in clinic. METHODS: Retrospective case series study.Four
      hundred and thirty-eight patients were diagnosed clinically as blepharitis in
      Beijing Tongren Hospital from Jan 2009 to July 2012. Analyzed the general states
      of health, case history, and the clinical manifestation, to summarize the
      clinical characteristics of blepharitis. The patients were clinically degree
      indexing and treated appropriately. After 1-2 courses of the treatment, the
      effect was analyzed.main outcome measures:manifestation of lid margin, corneal,
      conjunctiva, and the results of tear tests. RESULT: Four hundred and thirty-eight
      patients were recorded, from 3 to 84 years old, and the average was 40 +/- 18
      years old.435 (99.3%) cases were suffered with double eyes.159(26.3%) cases were
      males, and 279 (63.7%) cases were females. Children group had 41 cases (9.4%),
      which from 0 to 16 years old. Adult group (17-59 years) included 331 cases, which
      were 75.6% in the study. 66 cases were in aged group ( >= 60 years), being 15.0%
      in all cases.176 cases (40.2%) were on mild stage, 174 cases (39.7%) on middle
      stage, and 88 cases (20.1%) were on serious stage. Aged group were significantly
      more than children group (chi(2) = 34.575, P < 0.05).No significant difference
      between male and female (chi(2) = 32.877, P = 0.192). In 222 cases (50.7%)
      blepharitis patients complicated with correlation of keratoconjunctivitis
      lesions, respectively 8.5%, 75.3% and 86.4% in the mild, moderate, and severe
      patients. Adult group cases were significantly more than Children and aged group
      (chi(2) = 362.785, P < 0.05). Aged group were significantly more than Children
      group (chi(2) = 362.785, P < 0.05). 303 cases (69.2%)were with tear abnormal. The
      moderate and serious patients were more suffered with tear abnormal than mild
      patients (chi(2) = 64.438, P = 0.000). Patients were followed up for 1.5 to 27
      months, mean 8 months. According to different extent of blepharitis, patients
      were given 1 courses of treatment.333 cases were clinical recovery, and the other
      cases were improved obviously. CONCLUSIONS: Blepharitis occurs mainly in
      adults.It always complicate with dry eye and keratoconjunctival lesions.It is
      needed pay attention to by Ophthalmologist. The diagnosis and grade is based on
      typical clinical symptoms. The treatment according different grades should focus
      on the correct handling of the palpebral margin.

PMID- 24433689
TI  - [Preliminary clinical results of deep anterior lamellar keratoplasty in the
      treatment deep infectious purulent keratitis].
AB  - OBJECTIVE: To evaluate the clinical results of deep anterior lamellar
      keratoplasty (DALK) assisted by big bubble technique in the treatment of deep
      infectious purulent keratitis. METHODS: Seventeen patients (17 eyes) with deep
      infectious purulent keratitis received DALK surgery in Shandong Eye Hospital from
      January 2011 to March 2012. Case selection:Patients with purulent keratitis, the
      infection or infiltrate depth was more than four fifth corneal thickness;
      SURGICAL TECHNIQUE: Use DALK assisted by big bubble technique to cut off the
      lesions and expose the Descemet's membrane. The prepared donor which stored in D
      X medium or in glycerine preoperatively was oversized by 0.25 mm, and after
      stripping of Descemet's membrane, the donor button was interrupted sutured with
      10-0 nylon suture. The perioperative complications, recurrence, graft status and
      visual recovery were evaluated. RESULTS: The mean follow up time were 9 months.17
      patients with average age of (46 +/- 13) year old received DALK surgery,
      including 14 cases of fungal keratitis and 3 cases of bacteria keratitis.
      Perioperative complications:Two cases suffered micro perforation and were
      continuing performed DALK surgery after injecting air bubble in the anterior
      chamber. Three cases suffered double anterior chamber, one was resolved after
      graft resuture, and the other two were absorbed automatically.One patient
      suffered fungal recurrence and cured with secondary penetrating keratoplasty.
      Graft status:All grafts attached closely to the recipients, slit lamp and AS-OCT
      examinations were difficult to distinguish the interface. All of grafts were
      transparent. Visual acuity:before the operation best corrected visual acuity
      (BCVA) in patients with HM/20 cm to 3.7, after the surgery patients' BSCVA
      improved to 4.5-5.0. The mean astigmatism postoperatively of 16 cases received
      successful DALK finally was (4.53 +/- 2.35) D . CONCLUSIONS: For patients with
      deep infectious purulent keratitis, big bubble technique assistants DALK surgery
      is still a safe and effective method.

PMID- 24433690
TI  - [Corneal collagen crosslinking in the treatment of infectious keratitis].
AB  - OBJECTIVE: To investigate the feasibility and clinical efficacy of corneal
      collagen crosslinking (CXL) for the treatment of infectious keratitis. METHODS:
      Noncomparative interventional case series.19 patients with infectious keratitis
      admitted to our hospital between November 2011 and January 2012 were recruited
      into this study, CXL was performed when medications combined proved poor
      therapeutic effects. Postoperatively, the graft status, graft clarity, the visual
      prognosis and postoperative complications were recorded. RESULTS: In 15 cases,
      there was improvement in symptoms one week after operation.3 cases remained
      stable, while 1 case reported deteriorated function at the same time.One month
      after operation, Corneal melting was arrested and complete epithelialization was
      achieved in 13 cases, 5 cases experienced significant improvement and 1 patient
      experienced corneal ulcer perforation.2 month after surgery, patients with healed
      corneal ulcer increased to 17 cases, and 2 cases experienced corneal ulcer
      perforation. Those 17 cases with healed corneal ulcer were followed up for 6
      months, 15 cases had significant improvement in best-corrected visual acuity, 2
      cases had no significant change, and no relapse was observed in those 17 cases.
      CONCLUSION: Our experience based on the above and other cases suggest that CXL
      could be an effective tool in battling difficult cases of infectious keratitis.
      This treatment could present many advantages but will need further investigation
      both by in vitro and in vivo studies.

PMID- 24433691
TI  - [Corneal collagen cross-linking in the treatment of progressive keratoconus
      preliminary results].
AB  - OBJECTIVE: To evaluate the efficacy and safety of riboflavin-ultraviolet-A (UV-A)
      induced corneal collagen cross-linking (CXL) in the management of progressive
      keratoconus. METHODS: It was a retrospective case series study. Twenty-three eyes
      of 13 patients with progressive keratoconus were included. Corneal collagen
      crosslinking was performed under topical anesthesia including corneal de
      epithelization (8 mm diameter) and instillation of 0.1% riboflavin (in 20%
      dextran T500 solution) every 3 minutes for a total of 30 minutes. The irradiation
      is performed for another 30 min using a solid-state UV-A illuminator at 370 nm
      and an irradiance of 3 mW/cm(2). Average follow-up was 15.23 +/- 3.39 months
      (range: 12 to 22 months). Visual acuity, corneal topography, in vivo confocal
      microscopy, and endothelial cell count were evaluated at baseline and at 1, 3, 6,
      and 12 months follow-up. RESULTS: Mean uncorrected visual acuity(UCVA) and best
      spectacle-corrected visual acuity (BSCVA) increased 0.115 +/- 0.158 LogMAR (t =
      3.418, P = 0.0026) and 0.114 +/- 0.218 LogMAR (t = 2.441, P = 0.0236) 12 months
      postoperatively respectively. Interim analysis of treated eyes showed a
      flattening of the steepest simulated keratometry value (K-max) and astigmatism by
      an average of (1.893 +/- 3.713) diopters (D) (t = 2.391, P = 0.0262) and (0.117
      +/- 1.488) D (t = 0.370, P = 0.715) respectively at 12 months. Central corneal
      thickness decreased by (27.5 +/- 26.8) um (t = 4.812, P = 0.000) and (1.54 +/-
      19.4) um ( t = 0.147, P = 0.885) at one month and 12 months postoperatively
      respectively.Intraocular pressure, endothelial cell count, lens and fundus didn't
      change significantly at 12 months follow-up. CONCLUSIONS: CXL stabilised and
      improved the UCVA and BSCVA as well as the maximum k-readings at 1 year
      postoperatively in our cohort. It seems to be a safe and promising procedure to
      stop the progression of keratoconus.

PMID- 24433692
TI  - [Primary culture and morphological characteristics of human lacrimal adenoid
      cystic carcinoma cells].
AB  - OBJECTIVE: To explore a method of primary culturing human adenoid cystic
      carcinoma cells of lacrimal gland. METHODS: Experiment research. Tumor tissue was
      obtained from the surgical material of a patient diagnosed as lacrimal adenoid
      cystic carcinoma in Tianjin Medical University Eye Hospital during May 16th to
      June 1st.We gained primary cells via tissue culture techniques. Mixed cells were
      removed through several ways.Observed cell morphological characteristics by phase
      contrast microscope, scanning electron microscope and transmission electron
      microscope. Cyto-immunochemical staining was applied to detect the expressions of
      vimentin, desmin, S-100, cytokeratin, pan and CD34. Their expressions were also
      detected in the tumor tissue except CD34. Made cell growth curve and calculated
      cell doubling time. RESULTS: The outgrowth of cells was observed by day 5 after
      seeding tissues, and then cells generated slowly. The first passage proceeded by
      day 32, and the classical epithelioid cell colonies was observed by day 69 after
      inoculation. Purified cells of human lacrimal adenoid cystic carcinoma were
      obtained after the removal of mixed cells through several ways, which have been
      successfully subcultured for more than 100 passages. The 25th passage LACC cells
      appeared to be typically epithelioid cells, they showed contact inhibition as the
      density high enough.SEM and TEM showed the 25th passage LACC cells were malignant
      tumor cells poorly differentiated. They showed positive reaction with vimentin,
      cytokeratin (pan) as well as S-100, but negative reaction with desmin and CD34,
      which were consistent with the tumor tissue. The cell growth curve turned like a
      sigmoid one, and the cell doubling time was 37.1 h. CONCLUSIONS: We gained
      purified LACC cells, and understood the morphological characteristics, laying the
      foundation for the establishment of a human lacrimal adenoid cystic carcinoma
      cell line.

PMID- 24433693
TI  - [The study of new soft one-piece PHEMA keratoprosthesis implanted into alkali
      burned rabbits cornea].
AB  - OBJECTIVE: This study was to evaluate clinical results of two types soft one
      piece keratoprosthesis (KPros) made of PHEMA implanted to alkali burned rabbit
      corneas. METHODS: Experimental study. Twelve pieces KPros were implanted alkali
      burned rabbit corneas(type I and II, 6 pieces respectively). The examinations
      including slit-lamp, fundus photography,B-ultrasound and ultrasound biomicroscopy
      (UBM) were carried out. RESULTS: All Kpros were stable and no complications
      happened including conjunctiva flap dehiscence, aqueous leak and infection. IOP
      were normal by finger touch. B-ultrasound show no retina detachment and UBM show
      synechia in most animals (10 case). Retroprosthetic membrane happened in type I
      (3 case) . Visible conjunctiva hyperplasia covering the optical region happened
      in all KPros. CONCLUSIONS: (1) The same material, integrated design, maybe
      eliminating the material interface problem. (2)Simple surgical skills. (3)IOP
      measurement is possible because of soft material. (4)KPro I do not need removal
      of the lens and vitrectomy. The projecting portion of KPro II may reduce the
      incidence of proliferative membrane. Long term effects need more cases and
      further observation.

PMID- 24433694
TI  - [The expression level of MMP-2 and collagen of hydroxyapatite modified titanium
      for keratoprosthesis in the corneal stroma of rabbits].
AB  - OBJECTIVE: To investigate the expression level of metalloproteinases-2(MMP-2) and
      Collagen in a hydroxyapatite surfaced-modified of three Pan type titanium
      keratoprosthesis after that implanted into the corneal stroma of rabbits, further
      evaluate its biological compatibility. METHODS: Experimental study. Twenty-four
      New Zealand white rabbits, 2.0-2.5 kg, were respectively divided into three
      groups. Surgery was performed in right eye of all animals. skirt of HA-Ti and Ti
      were respectively inserted into the corneal stroma of rabbit of experimental
      group A and group B; only a sack was made without implantation in control group C
      . Cornea edema and corneal neovascularization were observed at scheduled times
      after operation; animals were sacrificed 2, 4 and 16 weeks after operation and
      their cornea was removed and examined under light microscopy; the surface of
      skirt was observed under scanning electron microscope. RESULTS: During the study
      period, all skirts were stable without infected, dissolved and excluded.
      Different degree of cornea edema and neovascularization was revealed after
      surgery. MMP-2 were absent in the normal corneal matrix. The expression level of
      MMP-2 in group A was higher than group C at all time points (F = 6.083, P <
      0.05), and was increased than group B at 4th (F = 47.074, P < 0.01), and was
      increased than group C at 16th weeks too (F = 6.079, P < 0.05) . Corneal
      organization has a large green 4 weeks type III collagen and yellow red type I
      collagen, 16 weeks corneal mainly for bright red when within the collagen type I,
      still have a small amount of collagen type III. CONCLUSIONS: Rabbit cornea
      implanted HA-Ti skirts cause MMP-2 activation, continuous high expression didn't
      cause the cornea to dissolve; Collagen -III turned into collagen-I gradually in
      the extracellular matrix around the skirts. Hydroxyapatite modified titanium for
      Keratoprosthesis promoted the corneal neovascularization and improve the
      interfacial bio integration of skirt and host cornea.

PMID- 24433695
TI  - [The role and mechanism of costimulatory molecule B7-H3 in the immune reaction of
      corneal transplantation in mice].
AB  - OBJECTIVE: To investigate the role of B7-H3 in the immune reaction of corneal
      transplantation in mice METHODS: Experimental study. Thirty Corneas of C57BL/6
      mice were orthotopically transplanted into the eyes of BALB/c mice, and graft
      survival was assessed on the basis of Sonoda's standard. When the RI grade was >=
      2, rejection was acknowledged and brought into the rejected group(R), and the
      others into the accepted group (A); 8 BALB/c Corneas into their own eyes belonged
      to isografts (I) ; In addition, 8 normal BALB/c mice were the control group (C) .
      At last, three eyes in each group (C, I, A, R groups) were used for HE staining
      and IHC of B7-H3, and there were five eyes in each group for qPCR to detect B7-H3
      mRNA expression. Repeated-measures analysis of variance (factorial analysis)
      followed by LSD test were used for post hoc analysis for expression differences
      of B7-H3 mRNA between groups. RESULTS: There were 9 accepted grafts and 21
      rejected grafts in 30 mice, and transplantation survival rate was 30% in the
      allograft group, while all grafts were transparent, and transplantation survival
      rate was 100% in the isografts. IHC results showed that B7-H3 was expressed on
      the corneal epithelium, endothelium and iris-ciliary body of both normal corneas
      and Isografts; B7-H3 expression increased in the accepted group and decreased in
      the rejected group . The results of qPCR conformed to the IHC; Repeated-measures
      analysis of variance (factorial analysis) followed by LSD test were used for post
      hoc analysis for differences between groups (F = 429.546) . there was a low B7-H3
      mRNA expression in the R group (3.89 +/- 0.037) and high expression in the A
      group (5.04 +/- 0.058); and C (4.30 +/- 0.023) ,I (4.33 +/- 0.031) groups had no
      significant difference (P = 0.387) ;But there was a significant difference
      between group R and C (P = 0.003)or group A and C(P = 0.001). CONCLUSION: All
      above show that B7-H3 may play an important role in the maintenance of ocular
      immune privilege.

PMID- 24433696
TI  - [Evaluation of calcium dobesilate for its anti-cataract potential in experimental
      rat models].
AB  - OBJECTIVE: To investigate the preventive and therapeutic effects of agent calcium
      dobesilate(CDO) with different doses on the galactose cataract of rats. METHODS:
      We chose fifty Wistar rats at 20- day old. Then, they were divided into 3 groups
      at random. Choose 10 rats as the control group and gave normal diet; 10 rats as
      the model group and fed with Gal solution ( drink 12.5% Gal solution from 1 to 7
      days and 10%Gal solution from 8 to 21 days except for normal diet ) ; 30 rats as
      the treatment group and fed with the same Gal solution as the model group,
      besides they were divided into high dosage group, medium dosage group and low
      dosage group equally and gave 300 mg*kg(-1)*d(-1), 150 mg*kg(-1)*d(-1), 75 mg*kg(
      1)*d(-1) dose of calcium dobesilate respectively from the first day to the end of
      experiment. The experiment lasts 21 days. Lens opacity were observed and recorded
      by slit-lamp examination regularly. Activity of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-px) and content of malondialdehyde (MDA) were
      determined to estimate the effect of CDO . Lens fibers changes and Histological
      changes were observed by scanning electron microscope (SEM) and light microscope
      (LM) separately. The apoptosis rate of lens epithelium were determined by TUNEL
      assay. RESULTS: The appearance of Lens opacity in model group was more quickly
      than that in treatment group in model group, 3 eyes in degree IV, 7 eyes in
      degree V, while in treatment group, 5 eyes in degree III, 3 eyes in degree IV, 2
      eyes in degree V (H = 7.12, P < 0.05). The activity of SOD and GSH-px in
      treatment group is higher than mode group, but lower than control group on 8th
      day, there was difference noticed in the activity of SOD (50.01 +/- 1.19), (39.39
      +/- 1.70) , treatment group (46.57 +/- 1.09, 46.42 +/- 0.87, 45.70 +/- 1.46)
      U/mgProt (F = 88.70, P < 0.05) and the activity of GSH-px (42.92 +/- 0.97) ,
      (12.70 +/- 1.17) , treatment group (29.16 +/- 1.05, 29.08 +/- 0.98, 28.25 +/-
      0.98) nmol/mgprot (F = 1071.89, P < 0.05) ]in 3 groups. The content of MDA in
      model group (3.43 +/- 0.15)nmol/mgprot is higher than treatment group (2.89 +/-
      0.11, 2.99 +/- 0.12, 2.99 +/- 0.09)nmol/mgprot (F = 64.62; P < 0.05). There were
      no statistic significant differences among high dosage group, medium dosage group
      and low dosage group . The texture of lens fibres detected by SEM in the rats of
      model was more disorder than treatment group. After HE staining, Lens epithelial
      cell detected by LM in control group have a clear structure, however, Lens
      epithelial cell both in model group and treatment group have changed from the
      initial single layer to multi-storey. Junction between lenses fibers became
      decreased even disappeared . The apoptosis rate of lens epithelium in treatment
      group[(2.37 +/- 0.17)%, (2.46 +/- 0.26)%, (2.79 +/- 0.41)%] is higher than
      control group (0.23 +/- 0.07) %, but is much fewer than model group (4.99 +/-
      0.51) % (chi(2) = 40.41;P < 0.05). CONCLUSION: CDO with different doses could
      protect lens of rats against galactose damage and there were no significant
      differences among the different doses of groups.

PMID- 24433697
TI  - [The research progress of biofilm and biofilm in eye disease].
AB  - Bacteria adherent on the active or inactive surface can form biofilms in which
      they are encased in a hydrated matrix of extracellular polymeric substances,
      which is so called bacterial biofilm (BBF). BBF has greater virulence and drug
      resistance, they can also evade the host immune system and lead to immune injury
      compared with planktonic bacteria. Many common medical infections involving
      ophthalmic infection are biofilm-associated. In this paper, the concept and
      biological characteristics of BBF and BBF-related ophthalmic infection were
      reviewed. 

PMID- 24433698
TI  - [Role of in vivo confocal microscopy in the management of infectious keratitis].
AB  - Infectious keratitis remains a severe ocular condition that can lead to
      irreversible complications and even blindness. An early diagnosis of an infective
      microorganism leading to effective treatment may improve the outcome of
      infectious keratitis.However, the accurate and rapid identification of the
      infectious agent remains a challenge for the ophthalmologist.In vivo confocal
      microscopy (IVCM) is a noninvasive imaging technique that provides high
      resolution images of ocular surface structures at a cellular level and infectious
      keratitis represents one of its most important clinical uses. The value of IVCM
      has been demonstrated in the diagnosis of acanthamoeba and filamentous fungal
      keratitis. The follow-up of such corneal infections may also be improved by this
      noninvasive imaging technique.However, the current resolution of IVCM limits its
      use in cases of bacterial and viral keratitis. 

PMID- 24433699
TI  - [The latest advance of correlation between autophagy and optic neuritis].
AB  - Optic neuritis is an inflammatory disease of the optic nerve with an abrupt loss
      of vision. The mechanism of the disease is not completely clear. Autophagy is an
      important metabolic pathway of eukaryotic cells involved degrading and recycling
      damaged organelles and proteins to maintain intracellular homeostasis. It is
      involved in the pathogenesis of various diseases. In this article, the probable
      effects of autophagy in the mechanism of optic neuritis is reviewed. 

PMID- 24433700
TI  - Isolation of high-purity anthocyanin mixtures and monomers from blueberries using
      combined chromatographic techniques.
AB  - Research on the isolation and preparation of anthocyanins has intensified in
      recent years because of the requirements of quantitative and bioactive analyses.
      However, simple and effective methods for the scale purification of pure
      anthocyanins from natural products are rarely reported. In this study, high
      purity anthocyanin mixtures and monomers were successfully isolated from wild
      blueberries using a combination of column chromatography and semi-preparative
      HPLC. We established an effective elution system to separate high-purity
      anthocyanin mixtures with aqueous ethanol containing 0.01% HCl first in an
      Amberlite XAD-7HP column (ethanol/H2O=35:65) and then in a Sephadex LH-20 column
      (ethanol/H2O=25:75). Crude anthocyanin extracts were isolated using the Amberlite
      column, and a purity of 32% was obtained based on UV-vis analysis. Three
      fractions of anthocyanin mixtures were isolated from the crude extracts using the
      Sephadex column with purities ranging from 59% to 68%. Three pure monomeric
      anthocyanins of malvidin-3-O-glucoside, petunidin-3-O-glucoside, and delphinidin
      3-O-glucoside were also isolated by semi-preparative HPLC and identified by HPLC
      DAD-ESI-MS/MS. The purities of these anthocyanins were determined by analytical
      HPLC and estimated to be 97.7%, 99.3%, and 95.4%, respectively. The results of
      this study may help promote the purification of anthocyanins from most blueberry
      varieties as well as from other plant materials. 

PMID- 24433701
TI  - Impact of the nature and composition of the mobile phase on the mass transfer
      mechanism in chiral reversed phase liquid chromatography. Application to the
      minimization of the solvent cost in chiral separations.
AB  - The mechanism of mass transfer was studied on a cellulose-based chiral stationary
      phase (CSP, Lux Cellulose-1) using aqueous mixtures of acetonitrile (50/50-90/10,
      v/v) or methanol (90/10 and 100/0, v/v) as the mobile phase. An experimental
      protocol validated in RPLC and HILIC chromatography and recently extended to
      chiral RPLC was applied. The five mass-transfer contributions (longitudinal
      diffusion, short-range and long-range eddy dispersion, solid-liquid mass transfer
      resistances due to finite intra-particle diffusivity and slow adsorption
      desorption) to the reduced height equivalent to a theoretical plate (HETP) were
      measured. The experimental results show that the adsorption rate constants kads
      of trans-stilbene enantiomers onto the CSP are three times larger with
      acetonitrile than with methanol as the organic modifier. This is correlated to
      the decrease of enantioselectivity from 1.4 (in methanol) to only 1.1 (in
      acetonitrile). The amount of solvent needed to achieve a separation factor of
      exactly 2.0 was determined. This showed that analysis cost could be reduced seven
      times by selecting pure methanol as the eluent for a 5cm long column rather than
      an acetonitrile-water mixture for a longer (20-45cm) column. 

PMID- 24433702
TI  - Homeopathy: where is the bias?

PMID- 24433703
TI  - Mechanisms underlying the neuronal-based symptoms of allergy.
AB  - Persons with allergies present with symptoms that often are the result of
      alterations in the nervous system. Neuronally based symptoms depend on the organ
      in which the allergic reaction occurs but can include red itchy eyes, sneezing,
      nasal congestion, rhinorrhea, coughing, bronchoconstriction, airway mucus
      secretion, dysphagia, altered gastrointestinal motility, and itchy swollen skin.
      These symptoms occur because mediators released during an allergic reaction can
      interact with sensory nerves, change processing in the central nervous system,
      and alter transmission in sympathetic, parasympathetic, and enteric autonomic
      nerves. In addition, evidence supports the idea that in some subjects this
      neuromodulation is, for reasons poorly understood, upregulated such that the same
      degree of nerve stimulus causes a larger effect than seen in healthy subjects.
      There are distinctions in the mechanisms and nerve types involved in allergen
      induced neuromodulation among different organ systems, but general principles
      have emerged. The products of activated mast cells, other inflammatory cells, and
      resident cells can overtly stimulate nerve endings, cause long-lasting changes in
      neuronal excitability, increase synaptic efficacy, and also change gene
      expression in nerves, resulting in phenotypically altered neurons. A better
      understanding of these processes might lead to novel therapeutic strategies aimed
      at limiting the suffering of those with allergies.

PMID- 24433704
TI  - Discerning mild cognitive impairment and Alzheimer Disease from normal aging:
      morphologic characterization based on univariate and multivariate models.
AB  - RATIONALE AND OBJECTIVES: Differentiating mild cognitive impairment (MCI) and
      Alzheimer Disease (AD) from healthy aging remains challenging. This study aimed
      to explore the cerebral structural alterations of subjects with MCI or AD as
      compared to healthy elderly based on the individual and collective effects of
      cerebral morphologic indices using univariate and multivariate analyses.
      MATERIALS AND METHODS: T1-weighted images (T1WIs) were retrieved from Alzheimer
      Disease Neuroimaging Initiative database for 116 subjects who were categorized
      into groups of healthy aging, MCI, and AD. Analysis of covariance (ANCOVA) and
      multivariate analysis of covariance (MANCOVA) were performed to explore the
      intergroup morphologic alterations indexed by surface area, curvature index,
      cortical thickness, and subjacent white matter volume with age and sex controlled
      as covariates, in 34 parcellated gyri regions of interest (ROIs) for both
      cerebral hemispheres based on the T1WI. Statistical parameters were mapped on the
      anatomic images to facilitate visual inspection. RESULTS: Global rather than
      region-specific structural alterations were revealed in groups of MCI and AD
      relative to healthy elderly using MANCOVA. ANCOVA revealed that the cortical
      thickness decreased more prominently in entorhinal, temporal, and cingulate
      cortices and was positively correlated with patients' cognitive performance in AD
      group but not in MCI. The temporal lobe features marked atrophy of white matter
      during the disease dynamics. Significant intercorrelations were observed among
      the morphologic indices with univariate analysis for given ROIs. CONCLUSIONS:
      Significant global structural alterations were identified in MCI and AD based on
      MANCOVA model with improved sensitivity. The intercorrelation among the
      morphologic indices may dampen the use of individual morphological parameter in
      featuring cerebral structural alterations. Decrease in cortical thickness is not
      reflective of the cognitive performance at the early stage of AD.

PMID- 24433705
TI  - Inducing sex reversal of the urogenital system of marsupials.
AB  - Marsupials differ from eutherian mammals in their reproductive strategy of
      delivering a highly altricial young after a short gestation. The young, with its
      undeveloped organ systems completes its development post-natally, usually within
      a pouch. The young is dependent on milk with a composition that varies through
      lactation to support its growth and changing needs as it matures over a lengthy
      period. Gonadal differentiation occurs after birth, providing a unique
      opportunity to examine the effects of hormonal manipulations on its sexual
      differentiation of the highly accessible young. In marsupials a difference in the
      migration of the urinary ducts around the genital ducts from eutherian mammals
      results in the unique tammar reproductive tract which has three vaginae and two
      cervices, and two distinctly separate uteri. In the tammar wallaby, a small
      member of the kangaroo family, we showed that virilisation of the Wolffian duct,
      prostate and phallus depends on an alternate androgen pathway, which has now been
      shown to be important for virilisation in humans. Through hormonal manipulations
      over differing time periods we have achieved sex reversal of both ovaries and
      testes, germ cells, genital ducts, prostate and phallus. Whilst we understand
      many of the mechanisms behind sexual differentiation there are still many lessons
      to be learned from understanding how sex reversal is achieved by using a model
      such as the tammar wallaby. This will help guide investigations into the major
      questions of how and why sex determination is achieved in other species. This
      review discusses the control and development of the marsupial urogenital system,
      largely drawn from our studies in the tammar wallaby and our ability to
      manipulate this system to induce sex reversal. 

PMID- 24433706
TI  - Characterization of ventricular myocardium in atrial fibrillation: looking where
      the light is best.

PMID- 24433708
TI  - Probing transmural myocardial perfusion with CMR.

PMID- 24433707
TI  - Diagnostic accuracy of stress perfusion CMR in comparison with quantitative
      coronary angiography: fully quantitative, semiquantitative, and qualitative
      assessment.
AB  - OBJECTIVES: This study's primary objective was to determine the sensitivity,
      specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic
      resonance (CMR) versus a reference standard of quantitative coronary angiography.
      We hypothesized that fully quantitative analysis of stress perfusion CMR would
      have high diagnostic accuracy for identifying significant coronary artery
      stenosis and exceed the accuracy of semiquantitative measures of perfusion and
      qualitative interpretation. BACKGROUND: Relatively few studies apply fully
      quantitative CMR perfusion measures to patients with coronary disease and
      comparisons to semiquantitative and qualitative methods are limited. METHODS:
      Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients
      with clinical indications for assessment of myocardial ischemia. Stress perfusion
      images alone were analyzed with a fully quantitative perfusion (QP) method and 3
      semiquantitative methods including contrast enhancement ratio, upslope index, and
      upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late
      gadolinium enhancement) were analyzed qualitatively with 2 methods including the
      Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by
      quantitative coronary angiography was considered abnormal. RESULTS: The optimum
      diagnostic threshold for QP determined by receiver-operating characteristic curve
      occurred when endocardial flow decreased to <50% of mean epicardial flow, which
      yielded a sensitivity of 87% and specificity of 93%. The area under the curve for
      QP was 92%, which was superior to semiquantitative methods: contrast enhancement
      ratio: 78%; upslope index: 82%; and upslope integral: 75% (p = 0.011, p = 0.019,
      p = 0.004 vs. QP, respectively). Area under the curve for QP was also superior to
      qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p <
      0.001 and p < 0.001 vs. QP, respectively). CONCLUSIONS: Fully quantitative stress
      perfusion CMR has high diagnostic accuracy for detecting obstructive coronary
      artery disease. QP outperforms semiquantitative measures of perfusion and
      qualitative methods that incorporate a combination of cine, perfusion, and late
      gadolinium enhancement imaging. These findings suggest a potential clinical role
      for quantitative stress perfusion CMR.

PMID- 24433709
TI  - Predicting long-term outcomes in asymptomatic or minimally symptomatic patients
      with HCM: back to basics.

PMID- 24433710
TI  - Impact of positive and negative lesion site remodeling on clinical outcomes:
      insights from PROSPECT.
AB  - OBJECTIVES: This study investigated coronary artery remodeling patterns
      associated with clinical outcomes. BACKGROUND: In the prospective, multicenter
      PROSPECT (Providing Regional Observations to Study Predictors of Events in the
      Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic
      Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse
      cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area
      (MLA) <=4 mm(2), a plaque burden >=70%, and a IVUS-virtual histology (VH) thin
      cap fibroatheroma (TCFA), but not lesion site remodeling. METHODS: Overall, 697
      consecutive patients with an acute coronary syndrome were enrolled and underwent
      3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The
      remodeling index (RI) was calculated as the external elastic membrane area at the
      MLA site divided by the average of the proximal and distal reference external
      elastic membrane areas. First, one third of the patients were randomly selected
      to determine RI cutoffs related to NCL MACE (development cohort). Receiver
      operating characteristic analysis showed that there were 2 separate cut points
      that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve =
      0.663). These cut points were used to define negative remodeling as an RI <0.88,
      intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an
      RI >1.00. Second, we used the remaining two-thirds of patients to validate these
      cut points with respect to lesion morphology and clinical outcomes (validation
      cohort). RESULTS: Kaplan-Meier curve analysis in the validation cohort showed
      that NCL MACE occurred more frequent (and equally) in negative and positive
      remodeling lesions compared with intermediate remodeling lesions. In this cohort,
      negative remodeling lesions had the smallest MLA, positive remodeling lesions had
      the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic
      cores, was most common in negatively remodeling lesions. CONCLUSIONS: The present
      study showed the novel concept that positive and negative lesion site remodeling
      was associated with unanticipated NCL MACE in the PROSPECT study. ( PROSPECT: An
      Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT];
      NCT00180466).

PMID- 24433711
TI  - Serial myocardial perfusion imaging: defining a significant change and targeting
      management decisions.
AB  - Myocardial perfusion imaging (MPI) with gated single-photon emission tomography
      provides important information on the extent and severity of myocardial perfusion
      abnormalities, including myocardial ischemia. The availability of software for
      automated quantitative assessment of myocardial perfusion in an objective and
      more reproducible manner than visual assessment has allowed MPI to be
      particularly effective in serial evaluation. Serial testing using MPI is widely
      used in guiding patient care despite the lack of well-defined appropriateness use
      criteria. This should not be surprising because ischemic heart disease is a life
      long malady subject to dynamic changes throughout its natural course and
      particularly following man-made interventions that may improve or worsen the
      disease process, such as medical therapy and coronary revascularization. Serial
      MPI has filled an important clinical gap by providing crucial information for
      managing patients with changes in clinical presentations or in anticipation of
      such changes in patients with stable symptoms. In the research arena, serial MPI
      has been widely applied in randomized controlled trials to study the impact of
      various medical and interventional therapies on myocardial perfusion, as well as
      the relative merits of new imaging procedures (hardware and/or software),
      radiotracers, and stressor agents. Serial testing, however, unlike initial or 1
      time testing, has more stringent requirements and is subject to variability
      because of technical, procedural, interpretational, and biological factors. The
      intrinsic variability of MPI becomes important in interpreting serial tests in
      order to define a true change in a given patient and to guide clinical decision
      making. The purpose of this first comprehensive review on this subject is to
      illustrate where serial MPI may be useful clinically and in research studies, and
      to highlight strategies for addressing the various issues that are unique to
      serial testing in order to derive more valid and robust data from the serial
      scans. 

PMID- 24433712
TI  - 3D real-time intracardiac echocardiographic visualization of atrial structures
      relevant to atrial fibrillation ablation.

PMID- 24433713
TI  - Integrated IVUS-OCT for real-time imaging of coronary atherosclerosis.

PMID- 24433714
TI  - Accelerated coronary plaque progression and endothelial dysfunction: serial
      volumetric evaluation by IVUS.

PMID- 24433715
TI  - Definitions of outcome, response and effect in imaging research to avoid
      confusion.

PMID- 24433716
TI  - Qualitative characterization of adipose tissue by MDCT.

PMID- 24433717
TI  - Myocardial extracellular volume measurement by cardiac magnetic resonance.

PMID- 24433718
TI  - Reply: Myocardial extracellular volume measurement by cardiac magnetic resonance.

PMID- 24433719
TI  - A LA mode atrioventricular mechanical coupling.

PMID- 24433720
TI  - Cardiovascular imaging physician certification in the era of multimodality
      imaging.

PMID- 24433721
TI  - Cellular and chemokine-mediated regulation in schistosome-induced hepatic
      pathology.
AB  - In hepatic schistosomiasis, pathology arises when schistosome eggs become lodged
      in the host liver, evoking an interleukin 4 (IL-4)- and IL-13-mediated dominant
      CD4(+) Th2 immune response. This response leads to the development of granulomas
      and fibrosis, with eosinophils, neutrophils, macrophages, hepatic stellate cells,
      and lymphocytes all identified as major cellular contributors to these events.
      This review outlines the cellular and molecular mechanisms of hepatic
      schistosomiasis, with an emphasis on the major cellular components and their
      release of chemokines. The differences between Schistosoma mansoni- and
      Schistosoma japonicum-induced hepatic granuloma are also discussed. This
      comprehensive overview of the processes associated with hepatic schistosomiasis
      may provide new insights into improved treatment for both schistosomiasis and
      other granulofibrotic diseases. 

PMID- 24433722
TI  - Synthesis of cubic Ia-3d mesoporous silica in anionic surfactant templating
      system with the aid of acetate.
AB  - Mesoporous silica with three-dimensional (3D) bicontinuous cubic Ia-3d structure
      and fascinating caterpillar-like morphology was synthesized by using anionic
      surfactant N-lauroylsarcosine sodium (Sar-Na) as the template and 3
      amionpropyltrimethoxysilane (APS) as the co-structure-directing agent (CSDA) with
      the aid of acetate. A phase transformation from high interfacial curvature 2D
      hexagonal to low interfacial curvature 3D cubic Ia-3d occurred in the presence of
      a proper amount of acetate. Other species of salts (excluding acetate) had the
      ability to induce the caterpillar-like morphology, but failed to induce the cubic
      Ia-3d mesostructure. Furthermore, [3-(2-aminoethyl)-aminopropyl]trimethoxysilane
      (DAPS) was also used as the CSDA to synthesize Ia-3d mesostructured silica under
      the aid of sodium acetate. After extraction of the anionic surfactants, amino and
      di-amine functionalized 3D bicontinuous cubic Ia-3d mesoporous silicas were
      obtained and used as supports to immobilize Pd nanoparticles for supported
      catalysts. The catalytic activity of the catalysts was tested by catalytic
      hydrogenation of allyl alcohol. 

PMID- 24433724
TI  - [Emphasis on standardization of molecular pathology laboratories].

PMID- 24433723
TI  - Assessing reproducibility of diffusion-weighted magnetic resonance imaging
      studies in a murine model of HER2+ breast cancer.
AB  - BACKGROUND AND PURPOSE: The use of diffusion-weighted magnetic resonance imaging
      (DW-MRI) as a surrogate biomarker of response in preclinical studies is
      increasing. However, before a biomarker can be reliably employed to assess
      treatment response, the reproducibility of the technique must be established.
      There is a paucity of literature that quantifies the reproducibility of DW-MRI in
      preclinical studies; thus, the purpose of this study was to investigate DW-MRI
      reproducibility in a murine model of HER2+ breast cancer. MATERIALS AND METHODS:
      Test-Retest DW-MRI scans separated by approximately six hours were acquired from
      eleven athymic female mice with HER2+ xenografts using a pulsed gradient spin
      echo diffusion-weighted sequence with three b values [150, 500, and 800s/mm(2)].
      Reproducibility was assessed for the mean apparent diffusion coefficient (ADC)
      from tumor and muscle tissue regions. RESULTS: The threshold to reflect a change
      in tumor physiology in a cohort of mice is defined by the 95% confidence interval
      (CI), which was+/-0.0972*10(-3)mm(2)/s (+/-11.8%) for mean tumor ADC. The
      repeatability coefficient defines this threshold for an individual mouse, which
      was+/-0.273*10(-3)mm(2)/s. The 95% CI and repeatability coefficient for mean ADC
      of muscle tissue were+/-0.0949*10(-3)mm(2)/s (+/-8.30%) and+/-0.266*10(
      3)mm(2)/s, respectively. CONCLUSIONS: Mean ADC of tumors is reproducible and
      appropriate for detecting treatment-induced changes on both an individual and
      mouse cohort basis.

PMID- 24433725
TI  - [The fourth edition of WHO classification of tumours of bone: an introduction].

PMID- 24433726
TI  - [Immunophenotypes and gene mutations in colorectal precancerous lesions and
      adenocarcinoma].
AB  - OBJECTIVE: To analyze immunophenotypes and gene mutations of colorectal
      precancerous lesions and adenocarcinoma, and to compare the difference of
      carcinogenetic mechanisms between the two precancerous lesions. METHODS: Fifty
      three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20
      sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January
      2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of
      colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20
      cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by
      immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins
      (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and
      PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50
      colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger
      sequencing. RESULTS: (1) Only 3 cases of hyperplastic polyps lost MLH1
      expression, and none of SSAs or traditional adenomas showed loss of MLH1. The
      negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA
      were significantly higher than those of traditional adenomas. (2) KRAS mutation
      was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps.
      (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF
      (6%, 3/50) and PIK3CA (4%, 2/50). CONCLUSIONS: Immunophenotypic and gene mutation
      profiles are different between colorectal serrated lesion and traditional
      adenoma. Alterations of MMR and MGMT expression play important roles in the
      pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic
      change in the early phase of colorectal carcinogenesis.

PMID- 24433727
TI  - [Mitotically active cellular fibroma of ovary: a clinicopathologic analysis].
AB  - OBJECTIVE: To study the clinicopathologic characteristics of mitotically active
      cellular fibroma (MACF) of the ovary. METHODS: The clinicopathologic features of
      11 cases of MACF from 2008 to 2012 years were retrospectively reviewed and
      immunohistochemic EnVision method was performed. RESULTS: The age of patients
      ranged from 21 to 65 years (mean = 46 years). The maximum tumor diameter varied
      from 6 to 16 cm (mean = 9.8 cm). The tumors were densely cellular and composed of
      intersecting bundles of spindle cells, sometimes associated with storiform
      pattern. The mitotic count ranged from 4 to 20 per 10 high-power field (mean =
      8.4). Atypical mitotic figures were not identified and coagulative tumor necrosis
      was not found. There was at most mild to moderate degree of nuclear atypia.
      Immunohistochemically, 8 cases showed positive stain for vimentin and 5 cases
      expressed diffusely or focally WT-1. In 6 cases, Ki-67 positive index ranged from
      5%-30%, including 1 case (10%), and 1 case (30%) in which mitotic figures were
      20/10 HPF. CK,AE1/AE3, CD117, CD34, CD99 and desmin were negative in the detected
      5 cases. Reticular fiber staining in 2 cases showed dense reticular fibers
      enveloping individual tumor cells. Ten patients who followed-up range from 4 to
      38 months were alive without evidence of recurrence or disease progression. One
      patient was alive with local recurrence 94 months after surgery. CONCLUSIONS:
      Cellular fibromatous neoplasm with mitotic count of >= 4/10 HPF but relatively
      bland nuclear features should be considered as MACF rather than ovarian
      fibrosarcoma. MACF is a group of ovarian tumor which carries a low malignant
      potential and occasional chance of recurrence.

PMID- 24433728
TI  - [Granulomatous lobular mastitis associated with mammary duct ectasia: a
      clinicopathologic study of 32 cases with review of literature].
AB  - OBJECTIVE: To study the clinicopathologic features of granulomatous lobular
      mastitis and mammary duct ectasia. METHODS: The clinicopathologic data from
      August 2005 to May 2013 of 32 cases of granulomatous lobular mastitis and mammary
      duct ectasia were retrospectively reviewed. RESULTS: The age of patients ranged
      from 26 to 45 years. Two patients had no history of delivery. Fourteen patients
      had no history of lactation or lactational disorder in the lesional side. Most of
      the remaining patients had history of breast feeding. Gross examination showed
      that the lesions were poorly circumscribed and varied from 3 to 12 cm in greatest
      dimension. Tiny abscess cavities, ranging from 0.1 to 0.5 cm in diameter and
      containing light yellowish to greyish secretion, were demonstrated. Histologic
      examination showed granuloma formation and ductal dilatation. Eleven patients had
      received antibiotic treatment. Twelve cases were complicated by sinus formation
      related to skin incision and drainage. The duration of follow-up ranged from 5 to
      90 months. Three cases showed ipsilateral recurrence and 3 cases had similar
      pathology in the contralateral breast. Four patients defaulted follow-up.
      CONCLUSIONS: Granulomatous lobular mastitis is associated with mammary duct
      ectasia. Accurate pathologic diagnosis is prudent for clinical management and
      control of local recurrence.

PMID- 24433729
TI  - [Factors related to biologic behavior in giant cell tumor of bone].
AB  - OBJECTIVE: To study the histogenesis of giant cell tumor (GCT) and factors
      related to tumor recurrence, invasiveness and malignant transformation. METHODS:
      The clinical features, radiologic classification, surgical approach, pathologic
      findings, immunophenotypes and follow-up data of 123 cases of GCT were analyzed.
      RESULTS: There was a significant correlation between tumor recurrence and
      radiographic classification (P = 0.032), over-expression of CD147 (P = 0.034) and
      p53 (P = 0.005), and surgical approach (P = 0.0048) in GCT. The biologic behavior
      showed no correlation with intramedullary infiltration, cortical bone
      involvement, parosteal soft tissue extension, tumor thrombi, fusiform changes of
      mononuclear tumor cells, mitotic count, Ki-67 index, coagulative tumor necrosis,
      secondary aneurysmal bone cyst formation, and adjoining bony reaction. The
      positive rate of p63 in stromal cells of GCT (79.7%, 94/118) was significantly
      higher than that in chondroblastoma (44.7%, 21/47), osteosarcoma (22.2%, 10/45)
      and other giant cell-rich tumors. CONCLUSIONS: GCT is a bone tumor of low
      malignant potential. It is sometimes characterized by locally invasive growth,
      active proliferation, coagulative necrosis, secondary aneurysmal bone cyst and
      surrounding bony reaction. It is difficult to predict the biologic behavior of
      GCT. Over-expression of p53 in the tumor cells and CD147 in all components of GCT
      correlate with tumor invasiveness, recurrence and malignant transformation.
      Selection of suitable surgical approach with reference to radiologic
      classification is considered as an important factor in reducing the recurrence
      rate.

PMID- 24433730
TI  - [Cutaneous regressing/regressed malignant melanoma: a clinicopathologic analysis
      of 8 cases].
AB  - OBJECTIVE: To study the clinicopathologic features and differential diagnosis of
      cutaneous regressing/regressed melanoma. METHODS: Histopathologic evaluation and
      immunohistochemical study by EnVision method were performed in 8 cases of
      cutaneous regressing/regressed melanoma. The clinical presentation, treatment and
      follow-up data were analyzed. RESULTS: The age of the patients ranged from 40 to
      69 years (mean 58 years). The male-to-female ratio was 3: 1. Tumors were located
      on the back (4 cases), sole of the foot (2 cases), ventral aspect of the toes (1
      case), and the forearm (1 case). Clinically, 6 patients presented with
      progressive black mole of the skin, followed by subsequent focal
      hypopigmentation, even scarring. Two patients presented with multiple foci of
      dark-brown pigmentation. Microscopically, 3 cases were completely regressed
      malignant melanoma. Tumoral melanosis was found in 1 of 3 cases. The other 5
      cases were melanoma with severe regression. The extent of regression ranged from
      75% to 90%. The Breslow depth of the tumors ranged from 0.5 to 1.0 mm.
      Immunohistochemically, both metastatic and primary tumor cells were diffusely
      positive for S-100, HMB45 and Melan A, while melanophages were positive for CD68.
      Follow-up data were available in 8 patients, ranging from 8 to 27 months. Five
      patients were alive with no evidence of disease, 1 patient was alive with stable
      disease and 2 patients died of metastatic melanoma. CONCLUSIONS: Correlation
      between clinical presentation and pathologic features is important for diagnosis
      of cutaneous regressing/regressed melanoma. Thin melanoma with extensive
      regression ( >= 75%) should not been regarded as low metastatic risk and wide
      excision combined with sentinel lymph node biopsy is recommended.

PMID- 24433731
TI  - [Clinicopathologic characteristics of sporadic renal hemangioblastoma].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics of sporadic
      renal hemangioblastoma. METHODS: Two cases of sporadic renal hemangioblastoma
      were studied by histological and immunohistochemical staining, along with review
      of the literature. RESULTS: Both cases were presented with a renal mass during
      annual physical examination with an age of 40 and 45 years, respectively. The
      lesions located in the middle portion of the kidney with a sharp tumor border.
      Histopathologically, the tumors were characterized by two major components:
      capillary and stromal cells. Immunohistochemically, the stromal cells were
      positive for vimentin, NSE, S-100 protein and inhibin-alpha, and negative for CK,
      HMB45, Melan A, EMA, CD56 and syn. Both tumors showed a very low level of Ki-67
      labeling. The endothelial cells were positive for CD34. CONCLUSION: Sporadic
      renal hemangioblastoma is a rare benign neoplasm, the diagnosis of which is based
      on the characteristic follicular architecture and an exclusion of other
      carcinomas of the kidney.

PMID- 24433732
TI  - [Primary mucosal tuberculosis of head and neck region: a clinicopathologic
      analysis of 47 cases].
AB  - OBJECTIVE: To study the clinicopathologic features, histologic diagnosis and
      differential diagnosis of primary mucosal tuberculosis (TB) in the head and neck
      region. METHODS: Forty-seven cases of primary mucosal TB of the head and neck
      region were studied by hematoxylin-eosin and Ziehl-Neelsen stains. The clinical
      and pathologic features were analyzed with review of the literature. RESULTS: The
      patients included 26 male and 21 female, with mean age 47.1 years (range 14-84
      years). There were three sinonasal TB, 19 nasopharyngeal TB, two oropharyngeal
      TB, 18 laryngeal TB, four middle ear TB, one salivary gland TB and one laryngeal
      TB complicating laryngeal cancer. The initial symptoms were nasal obstruction,
      mucopurulent rhinorrhea, epistaxis, snoring, hoarseness, dysphagia, odynophagia,
      serous otitis, hearing loss, tinnitus, and otalgia. Physical examination result
      was variable, from an apparently normal mucosa, to an evident mass, or a mucosa
      with an adenotic or swollen appearance, ulcers, leukoplakic areas, and various
      combinations thereof. CT and MRI findings included diffuse thickening, a soft
      tissue mass, calcification within the mass and bone destruction resembling
      malignancy. Histologic examination showed granulomas with a central necrotic
      focus surrounded by epithelioid histiocytes and multinucleated Langhan's giant
      cells. Acid-fast bacilli were difficult to demonstrate but found in 13/45 cases.
      Follow-up data were available in 42 patients. CONCLUSIONS: Primary TB arising in
      the head and neck mucosa is rare. It may mimic or co-exist with other conditions.
      The characteristic histopathology is a granuloma with central caseous necrosis
      and Langhans'giant cells. Identification of acid-fast bacilli and bacteriologic
      culture confirm the diagnosis of mycobacterial disease.

PMID- 24433733
TI  - [Effect of down-regulation of HE4 gene expression on biologic behavior of ovarian
      cancer cells].
AB  - OBJECTIVE: To investigate the effects of HE4 gene knockdown on the proliferation,
      adhesion and invasion of the ovarian cancer cells SKOV3. METHODS: The knockdown
      of HE4 gene was performed by RNAi technology. The recombinant plasmids (pSUPER
      HE4 shDNAs) were constructed and transfected into human ovarian cancer cells
      SKOV3. HE4 expression was then identified by real-time PCR and Western blot
      analysis. The invasion and adhesion ability of transduced cells were determined.
      In addition, cell proliferation and growth were analyzed by colonies formation
      assay. RESULTS: Knockdown of HE4 was achieved, and further confirmed by real-time
      PCR and Western blot. The proliferation of HE4-down-regulated cells was not
      affected, but the invasion ability of the transfected cells was reduced (P <
      0.05) and the adhesion ability was also reduced to 27.3%. CONCLUSION: HE4
      expression is down-regulated effectively by the constructed HE4 shDNA, and thus
      knockdown of HE4 inhibits the adhesion and invasion of SKOV3 cells.

PMID- 24433734
TI  - [Secretory adenocarcinoma of lung with brain metastasis: report of a case].

PMID- 24433735
TI  - [Intravascular papillary endothelial hyperplasia of small intestine: report of a
      case].

PMID- 24433736
TI  - [Renal schwannoma with peripheral lymphocytic cuffing: report of a case].

PMID- 24433737
TI  - [Mixed epithelial and stromal tumor of kidney in male patient: report of a case].

PMID- 24433738
TI  - [Central mucoepidermoid carcinoma of oral cavity: report of a case].

PMID- 24433739
TI  - [B/T-cell biphenotypic lymphoblastic lymphoma/leukemia: report of a case].

PMID- 24433740
TI  - [Temporal-parietal medulloepithelioma: report of a case].

PMID- 24433741
TI  - [Clinical significance and management approach of endometrial cells detected by
      cervical Pap cytology].

PMID- 24433742
TI  - [Updates on inflammatory myofibroblastic tumor of head and neck region].

PMID- 24433743
TI  - [1, 25(OH)2D3 and pulmonary fibrosis].

PMID- 24433744
TI  - A home telehealth program for patients with severe COPD: the PROMETE study.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOP)
      are key events in the natural history of the disease. Patients with more AECOPD
      have worse prognosis. There is a need of innovative models of care for patients
      with severe COPD and frequent AECOPD, and Telehealth (TH) is part of these
      programs. METHODS: In a cluster assignment, controlled trial study design, we
      recruited 60 patients, 30 in home telehealth (HT) and 30 in conventional care
      (CC). All participants had a prior diagnosis of COPD with a post-bronchodilator
      forced expiratory volume (FEV1)% predicted <50%, age >= 50 years, were on long
      term home oxygen therapy, and non-smokers. Patients in the HT group measured
      their vital signs on a daily bases, and data were transmitted automatically to a
      Clinical Monitoring Center for followed-up, and who escalated clinical alerts to
      a Pneumologist. RESULTS: After 7-month of monitoring and follow-up, there was a
      significant reduction in ER visits (20 in HT vs. 57 in CC), hospitalizations (12
      vs. 33), length of hospital stay in (105 vs. 276 days), and even need for non
      invasive mechanical ventilation (0 vs. 8), all p < 0.05. Time to the first severe
      AECOPD increased from 77 days in CC to 141 days in HT (K-M p < 0.05). There was
      no study withdrawals associated with technology. All patients showed a high level
      of satisfaction with the HT program. CONCLUSIONS: We conclude that HT in elderly,
      severe COPD patients with multiple comorbidities is safe and efficacious in
      reducing healthcare resources utilization.

PMID- 24433745
TI  - Comparison of fractional wave equations for power law attenuation in ultrasound
      and elastography.
AB  - A set of wave equations with fractional loss operators in time and space are
      analyzed. The fractional Szabo equation, the power law wave equation and the
      causal fractional Laplacian wave equation are all found to be low-frequency
      approximations of the fractional Kelvin-Voigt wave equation and the more general
      fractional Zener wave equation. The latter two equations are based on fractional
      constitutive equations, whereas the former wave equations have been derived from
      the desire to model power law attenuation in applications like medical
      ultrasound. This has consequences for use in modeling and simulation, especially
      for applications that do not satisfy the low-frequency approximation, such as
      shear wave elastography. In such applications, the wave equations based on
      constitutive equations are the viable ones. 

PMID- 24433746
TI  - Albumin acts like transforming growth factor beta1 in microbubble-based drug
      delivery.
AB  - Unlike lipid-shelled microbubbles (MBs), albumin-shelled microbubbles (MBs) have
      not been reported to be actively targeted to cells without the assistance of
      antibodies. Recent studies indicate that the albumin molecule is similar to
      transforming growth factor beta (TGF-beta) both structurally and functionally.
      The TGF-beta superfamily is important during early tumor outgrowth, with an
      elevated TGF-beta being tumor suppressive; at later stages, this switches to
      malignant conversion and progression, including breast cancer. TGF-beta receptors
      I and II play crucial roles in both the binding and endocytosis of albumin.
      However, until now, no specific albumin receptor has been found. On the basis of
      the above-mentioned information, we hypothesized that non-antibody-conjugated
      albumin-shelled MBs can be used to deliver drugs to breast cancer cells. We also
      studied the possible roles of TGF-beta1 and radiation force in the behavior of
      cells and albumin-shelled MBs. The results indicate that albumin-shelled MBs
      loaded with paclitaxel (PTX) induce breast cancer cell apoptosis without the
      specific targeting produced by an antibody. Applying either an acoustic radiation
      force or cavitation alone to cells with PTX-loaded albumin MBs increased the
      apoptosis rate to 23.2% and 26.3% (p < 0.05), respectively. We also found that
      albumin-shelled MBs can enter MDA-MB-231 breast cancer cells and remain there for
      at least 24 h, even in the presence of PTX loading. Confocal micrographs revealed
      that 70.5% of the breast cancer cells took up albumin-shelled MBs spontaneously
      after 1 d of incubation. Applying an acoustic radiation force further increased
      the percentage to 91.9% in our experiments. However, this process could be
      blocked by TGF-beta1, even with subsequent exposure to the radiation force. From
      these results, we conclude that TGF-beta1 receptors are involved in the
      endocytotic process by which albumin-shelled MBs enter breast cancer cells. The
      acoustic radiation force increases the contact rate between albumin-shelled MBs
      and tumor cells. Combining a radiation force and cavitation yields an apoptosis
      rate of 31.3%. This in vitro study found that non-antibody-conjugated albumin
      shelled MBs provide a useful method of drug delivery. Further in vivo studies of
      the roles of albumin MBs and TGF-beta in different stages of cancer are
      necessary.

PMID- 24433747
TI  - Measuring absolute blood pressure using microbubbles.
AB  - Gas microbubbles are highly compressible, which makes them very efficient sound
      scatterers. As another consequence of their high compressibility, the radii of
      the microbubbles are affected by the pressure of the fluid around them, which
      changes their resonance frequency. Although the pressures present within the
      human body cause only minor variations in the radii of uncoated microbubbles
      (~0.2% per 10 mmHg) and, therefore, very small variations in the resonance
      frequency (~1 kHz per 10 mmHg), it was found in the work described here, through
      both simulations and in vitro measurements, that large changes in resonance
      frequency can occur in phospholipid-coated microbubbles for small blood pressure
      variations because of the exotic buckling dynamics of phospholipid monolayers (up
      to 240 kHz per 10 mmHg). This method should allow non-invasive measurement of the
      gauge blood pressure in deep blood vessels as long as the microbubble physical
      properties are well controlled.

PMID- 24433748
TI  - Characterization of acoustic droplet vaporization for control of bubble
      generation under flow conditions.
AB  - This study investigated the manipulation of bubbles generated by acoustic droplet
      vaporization (ADV) under clinically relevant flow conditions. Optical microscopy
      and high-frequency ultrasound imaging were used to observe bubbles generated by 2
      MHz ultrasound pulses at different time points after the onset of ADV. The
      dependence of the bubble population on droplet concentration, flow velocity,
      fluid viscosity and acoustic parameters, including acoustic pressure, pulse
      duration and pulse repetition frequency, was investigated. The results indicated
      that post-ADV bubble growth spontaneously driven by air permeation markedly
      affected the bubble population after insonation. The bubbles can grow to a stable
      equilibrium diameter as great as twice the original diameter in 0.5-1 s, as
      predicted by the theoretical calculation. The growth trend is independent of flow
      velocity, but dependent on fluid viscosity and droplet concentration, which
      directly influence the rate of gas uptake by bubbles and the rate of gas exchange
      across the wall of the semipermeable tube containing the bubbles and, hence, the
      gas content of the host medium. Varying the acoustic pressure does not markedly
      change the formation of bubbles as long as the ADV thresholds of most droplets
      are reached. Varying pulse duration and pulse repetition frequency markedly
      reduces the number of bubbles. Lengthening pulse duration favors the production
      of large bubbles, but reduces the total number of bubbles. Increasing the PRF
      interestingly provides superior performance in bubble disruption. These results
      also suggest that an ADV bubble population cannot be assessed simply on the basis
      of initial droplet size or enhancement of imaging contrast by the bubbles.
      Determining the optimal acoustic parameters requires careful consideration of
      their impact on the bubble population produced for different application
      scenarios. 

PMID- 24433750
TI  - Response to letter.

PMID- 24433749
TI  - Axial transmission method for long bone fracture evaluation by ultrasonic guided
      waves: simulation, phantom and in vitro experiments.
AB  - Mode conversion occurs when the ultrasonic guided waves encounter fractures. The
      aim of this study was to investigate the feasibility of fracture assessment in
      long cortical bone using guided-mode conversion. Mode conversion behavior between
      the fundamental modes S0 and A0 was analyzed. The expressions proposed for modal
      velocity were used to identify the original and converted modes. Simulations and
      phantom experiments were performed using 1.0-mm-thick steel plates with a notch
      width of 0.5 mm and notch depths of 0.2, 0.4, 0.6 and 0.8 mm. Furthermore, in
      vitro experiments were carried out on nine ovine tibias with 1.0-mm-wide partial
      transverse gap break and cortical thickness varying from 2.10 to 3.88 mm. The
      study confirmed that mode conversion gradually becomes observable as fracture
      depth increases. Energy percentages of the converted modes correlated strongly
      with fracture depth, as illustrated by the frequency-sweeping experiments on
      steel phantoms (100-1100 kHz, r(2) = 0.97, p < 0.0069) and the fixed-frequency
      experiments on nine ovine tibias (250 kHz, r(2) = 0.97, p < 0.0056). The
      approaches described, including mode excitation, velocity expressions and energy
      percentage criteria, may also contribute to ultrasonic monitoring of long bone
      fracture healing.

PMID- 24433751
TI  - A curious chest radiograph after line placement.

PMID- 24433752
TI  - Safety of transcardiac conducted electrical weapon probe deployments remains
      unclear.

PMID- 24433753
TI  - Measuring health-related quality of life in men with prostate cancer: A
      systematic review of the most used questionnaires and their validity.
AB  - OBJECTIVES: To identify and study the psychometric properties of the most used
      health-related quality-of-life (HRQoL) instruments in men with prostate cancer.
      METHODS: We performed a literature search using PubMed and EMBASE to identify all
      studies on prostate cancer using a HRQoL instrument. The most often used HRQoL
      instruments were investigated in detail by 2 independent reviewers. Data were
      extracted regarding the characteristics and psychometric values of the
      instruments, i.e., content validity, internal consistency, criterion validity,
      construct validity, reproducibility, responsiveness, floor and ceiling effects,
      and interpretability. Good psychometric outcomes indicate a high methodological
      quality of the instrument. RESULTS: Our systematic search revealed 13,812
      potential relevant articles, of which 2,258 appeared relevant after screening the
      titles and reading the abstracts. We studied the psychometric properties of the
      20 most often used HRQoL instruments, the first 3 of which were the Expanded
      Prostate Index Composite, University of California-Los Angeles Prostate Cancer
      Index, and Short Form-36 (SF-36). Content validity, internal consistency
      (alpha>0.70), criterion validity, construct validity, and reproducibility were
      good in 60%, 90%, 10%, 35%, and 65% of the 20 instruments, respectively.
      Responsiveness was not reported for 12 of 20 instruments (60%). Floor and ceiling
      effects and the interpretability of the questionnaires were only reported in 3
      (15%) and 6 (30%) instruments. CONCLUSIONS: Considering the psychometric
      properties, we advise to use the SF-12 as a generic instrument, the Cancer
      Rehabilitation Evaluation System-SF or the Functional Assessment of Cancer
      Therapy-General as cancer-specific HRQoL instruments, and the University of
      California-Los Angeles Prostate Cancer Index, the QUFW94, or the Functional
      Assessment of Cancer Therapy-Prostate as prostate cancer-specific instruments.

PMID- 24433754
TI  - Combining smoking information and molecular markers improves prognostication in
      patients with urothelial carcinoma of the bladder.
AB  - OBJECTIVES: Tissue-based markers improve the accuracy of prediction models in
      urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative
      exposure also affect outcomes. To evaluate whether the combination of molecular
      markers and smoking features further improved the prognostication of patients who
      underwent radical cystectomy (RC) for UCB. MATERIALS AND METHODS: A total of 588
      patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005.
      Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on
      tissue microarrays from the RC specimen. Smoking features were routinely assessed
      at diagnosis. Multivariable Cox regression models assessed time to disease
      recurrence and cancer-specific mortality. RESULTS: Of the 588 patients, 128 were
      never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227
      patients experienced disease recurrence, whereas 190 died of UCB. Smoking status
      was independently associated with both outcomes (hazard ratio [HR] = 1.48 and
      2.62, for former and current vs. never smokers, respectively, P<0.001). All
      markers were significantly associated with both outcomes (P<0.05) except for
      survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27
      increased the discrimination of clinicopathologic model for former and current
      vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c
      indices of 0.741 and 0.740 for former and current vs. never smokers,
      respectively). The further addition of smoking features and biomarker status
      improved the discrimination of the model (c-indices of 0.783 and 0.786 for former
      and current vs. never smokers, respectively). CONCLUSIONS: We confirmed that
      smoking information and tissue markers status improve prognostication of UCB
      outcomes after RC; the combination of both reaching the highest level of
      discrimination.

PMID- 24433755
TI  - A cautionary note against embryo aneuploidy risk assessment using time-lapse
      imaging.
AB  - Preimplantation genetic screening (PGS) for embryo aneuploidy using embryo biopsy
      is a widely available technique used to select embryos for transfer following IVF
      for certain patient populations. Since its introduction, there has been an
      ongoing search for a non-invasive technique to perform PGS. Such an advance would
      revolutionize the field of IVF enabling PGS to be used universally as a routine
      embryo selection tool with the potential to significantly increase pregnancy
      rates and decrease poor outcomes such as miscarriage. Recent publications
      illustrating the development of an algorithm using time-lapse imaging of IVF
      embryos have claimed to have done just this. We believe that the statements made
      in these articles, which include the proposed ability to increase pregnancy rates
      by determining embryo aneuploidy risk by time-lapse imaging, are premature and to
      this point unsubstantiated by the published data. We provide evidence from
      existing publications and from our own data that suggests that the statements
      recently made are misleading. We make the point that further investigation is
      needed either in the form of a larger, age-adjusted data set or preferably in a
      randomized controlled trial. 

PMID- 24433756
TI  - Cumulative pregnancy and live birth rates after IVF.

PMID- 24433757
TI  - The timing of monozygotic twinning: a pro-life challenge to conventional
      scientific wisdom.
AB  - A recent paper in Zygote criticizes the 'theory of origins' of the various
      classes of monozygotic twins originally proposed and developed by Corner. It does
      so on the basis of recent observations on human IVF embryos. Here, the validity
      of one of the evidential sources is upheld, but an alternative explanation is
      proposed that is more plausibly based on evidence than the explanation offered in
      Zygote. 

PMID- 24433758
TI  - Automatic cervical cell segmentation and classification in Pap smears.
AB  - Cervical cancer is one of the leading causes of cancer death in females
      worldwide. The disease can be cured if the patient is diagnosed in the pre
      cancerous lesion stage or earlier. A common physical examination technique widely
      used in the screening is Papanicolaou test or Pap test. In this research, a
      method for automatic cervical cancer cell segmentation and classification is
      proposed. A single-cell image is segmented into nucleus, cytoplasm, and
      background, using the fuzzy C-means (FCM) clustering technique. Four cell classes
      in the ERUDIT and LCH datasets, i.e., normal, low grade squamous intraepithelial
      lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), and squamous
      cell carcinoma (SCC), are considered. The 2-class problem can be achieved by
      grouping the last 3 classes as one abnormal class. Whereas, the Herlev dataset
      consists of 7 cell classes, i.e., superficial squamous, intermediate squamous,
      columnar, mild dysplasia, moderate dysplasia, severe dysplasia, and carcinoma in
      situ. These 7 classes can also be grouped to form a 2-class problem. These 3
      datasets were tested on 5 classifiers including Bayesian classifier, linear
      discriminant analysis (LDA), K-nearest neighbor (KNN), artificial neural networks
      (ANN), and support vector machine (SVM). For the ERUDIT dataset, ANN with 5
      nucleus-based features yielded the accuracies of 96.20% and 97.83% on the 4-class
      and 2-class problems, respectively. For the Herlev dataset, ANN with 9 cell-based
      features yielded the accuracies of 93.78% and 99.27% for the 7-class and 2-class
      problems, respectively. For the LCH dataset, ANN with 9 cell-based features
      yielded the accuracies of 95.00% and 97.00% for the 4-class and 2-class problems,
      respectively. The segmentation and classification performances of the proposed
      method were compared with that of the hard C-means clustering and watershed
      technique. The results show that the proposed automatic approach yields very good
      performance and is better than its counterparts. 

PMID- 24433759
TI  - Journees Francaises de Radiologie 2014: changes planned.

PMID- 24433760
TI  - Appendiceal mucinous cystadenoma.

PMID- 24433761
TI  - [The thinking on the development of foot and ankle surgery based on macro
      thinking concept].

PMID- 24433762
TI  - [HER2 testing in breast cancer: rereading the ASCO/CAP guideline].

PMID- 24433763
TI  - [Multivariate analysis of the efficacy of laparoscopic splenectomy in the
      treatment of immune thrombocytopenic purpura].
AB  - OBJECTIVE: To identify factors that can effectively predict the efficacy of
      laparoscopic splenectomy (LS) in the treatment of immune thrombocytopenic purpura
      (ITP). METHODS: From January 2007 to September 2012, 78 patients with ITP
      underwent laparoscopic splenectomy were retrospectively analyzed. According to
      the postoperative platelet (PLT) count and haemorrhagic manifestations, they were
      divided into effective group and ineffective group. Nine influencing factors were
      univariate analyzed and multivariate analyzed. RESULTS: In effective group (65
      cases) and ineffective group (13 cases), average PLT count of 1 day before
      surgery was 47*10(9)/L vs. 21*10(9)/L, average operative time was (166 +/- 46)
      minutes vs. (139 +/- 29) minutes. Univariate analysis result: PLT count of 1 day
      before surgery (Z = -2.776, P = 0.005) and operative time (t = 2.723, P = 0.011)
      was statistically significant in 2 groups, the rest factors did not significantly
      influence the result. Multivariate analysis revealed that only PLT count of 1 day
      before surgery was statistically significant (OR = 0.964, 95%CI: 0.932-0.997, P =
      0.031) in 2 groups, but operative time (P = 0.051) was not statistically
      significant. CONCLUSIONS: PLT count of 1 day before surgery is a predict factor
      in LS for ITP. Because of the limited sample number, further multi-center
      prospective study with large sample is warrant.

PMID- 24433764
TI  - [Analysis of the clinicopathologic characters and prognostic impact of extranodal
      metastasis in gastric cardia patients].
AB  - OBJECTIVE: To investigate the correlation between extranodal metastasis (EM) and
      clinicopathologic features as well as the effect of EM on the prognosis in
      gastric cardia patients. METHODS: Retrospective analysis was performed for the
      323 cases with histologically proven adenocarcinoma of gastric cardia who
      underwent curative resection from January 2000 to January 2007. There were 272
      male patients and 51 female patients with their median age of 63 (22 to 85)
      years. The relationship between clinicopathological features and extranodal
      metastasis was studied. The effects of the EM on the recurrence and survival of
      these patients were also analyzed. RESULTS: EM positive was detected in 67
      (20.7%) of the 323 patients. The incidence of EM was correlated with tumor Lauren
      typing, differentiation degree, invasive depth and lymph node metastasis (chi(2)
      = 4.647-27.216, P < 0.05). The 5-year survival rate and media survival time
      between patients with EM and those without EM were 12.3%, 34.1% and 20, 39
      months, there was a statistically significantly difference (chi(2) = 23.936, P =
      0.000) in 5-year survival rate. Multivariate analysis identified that invasive
      depth, lymph node metustasis and EM as an independent prognostic factor of all
      the patients. To the last follow up, the cumulative probability of recurrence of
      EM-positive patients was significant higher than EM-negative patients (59.7% vs.
      35.9%; chi(2) = 12.409, P = 0.000). To study furthermore, stratified analysis
      showed that, in the node-positive patients, the cumulative recurrence rate of EM
      positive patients was higher than EM-negative patients (60.9% vs. 40.0%; chi(2) =
      8.410, P = 0.004) and the 5-year survival rate of EM-positive patients was less
      than the EM-negative patients (12.9% vs. 30.1%; chi(2) = 12.939, P = 0.000), the
      differences were statistically significant. CONCLUSIONS: EM positive is
      determined to be an independent prognosis factor of gastric cardia after curative
      resection. EM-positive patients have a high risk for recurrence and a short time
      to live.

PMID- 24433765
TI  - [Clinical analysis of primary hyperparathyroidism with kidney stones: 23 cases
      report].
AB  - OBJECTIVE: To discuss the clinical characteristics of primary hyperparathyroidism
      (PHPT) with kidney stones. METHODS: The clinical data of 23 cases undergoing
      diagnostic evaluation and surgery for PHPT combined with kidney stones between
      January 2004 and February 2012 was retrospectively analyzed. The 23 cases had
      undergone preoperative parathyroid neck color ultrasound, CT or (99)mTc-methoxy
      isobutyl isonitrile ((99)mTc-MIBI) diagnosis. The surgical treatment included
      parathyroid disease and kidney stones. The intravenous calcium, phosphorus and
      serum intact parathyroid hormone (iPTH) levels, 24 hours urinary calcium
      concentrations were measured 3 days before and 7 days after surgery. RESULTS:
      There were 8 male and 15 female patients. The stone diameter were (3.2 +/- 0.7)
      cm (range 2.1-4.0 cm). All patients did both parathyroid surgery and kidney
      surgery. The statistical discrepancy of serum calcium (there were (3.31 +/- 0.39)
      mmol/L before surgery and (2.12 +/- 0.18) mmol/L at 7 days after surgery, t =
      11.26), serum phosphorus ((0.70 +/- 0.09) and (1.21 +/- 0.21) mmol/L in before
      and after surgery respectively, t = 10.53), iPTH (there were (28.8 +/- 10.0)
      pmol/L before surgery and (3.6 +/- 2.6) pmol/L after surgery, t = 12.83) and 24
      hours urine calcium (there were (7.2 +/- 3.1) mmol/d before surgery and (3.6 +/-
      2.5) mmol/d after surgery, t = 8.81) before and after the operation was
      significant (all P < 0.01). PTH concentration with serum calcium concentration
      correlation coefficient was r = 0.59 (P < 0.01). Eighteen patients (78.3%) had
      solitary parathyroid adenomas, two patients (8.7%) had multiple parathyroid
      adenomas, and three patients (13.0%) had multiglandular hyperplasia confirmed at
      surgery and histology. During follow-up, 8 patients had stone recurrence and 3
      patients were did operation again to deal with renal stone within 2 years. Among
      them, 7 cases were normal, 1 case of parathyroid adenomas recurrence and
      reoperation. CONCLUSIONS: The parathyroid operation may reduce the calculus
      recurrence remarkably. Early diagnosis and treatment of primary
      hyperparathyroidism is helpful to reduce the calculus recurrence and preserve the
      renal function.

PMID- 24433766
TI  - [Prognostic factors predicting postoperative survival period in the treatment of
      primary retroperitoneal leiomyosarcoma].
AB  - OBJECTIVE: To evaluate prognostic factors predicting postoperative period for
      patients with primary retroperitoneal leiomyosarcoma. METHODS: The clinical data
      and prognosis of 35 patients with primary retroperitoneal leiomyosarcoma between
      August 2002 and June 2011 were retrospectively reviewed and analyzed. RESULTS:
      The resectability rate of primary tumors was 91.4% (32/35) , and 71.4% (25/35) of
      the patients underwent complete resection. The 21 patients (84.0%) who got a
      complete resection of the primary tumor got tumor recurrence and died of tumor
      recurrence eventually. The overall 1-, 3-, 5-year survival rate were 82.9%, 54.3%
      and 31.4% and the median survival was 36 months. In the analysis of factors
      influencing postoperative survival, factors associated with postoperative survive
      were modus operandi of the tumor resection (chi(2) = 16.871, P = 0.000), tumor
      size (chi(2) = 5.548, P = 0.019) and tumor grade (chi(2) = 8.080, P = 0.014); the
      difference between age (chi(2) = 0.073, P = 0.787), gender (chi(2) = 2.181, P =
      0.140) and adjuvant therapy (chi(2) = 1.344, P = 0.511) got no statistical
      significance. CONCLUSIONS: The efficiency of adjuvant therapy for primary
      retroperitoneal leiomyosarcoma is not clear, complete resection remains the
      mainstream for primary leiomyosarcoma. Incomplete resection, large tumor (tumor
      diameter >= 10 cm) and high grade tumor predict shorter postoperative survival
      period.

PMID- 24433767
TI  - [Correlation between the shifting of medulla oblongata and cerebellum and syrinx
      resolution after posterior fossa decompression in Chiari malformation].
AB  - OBJECTIVES: To evaluate the changes of the position of medulla oblongata and
      cerebellum following posterior fossa decompression (PFD), and to investigate
      their influences on the prognosis of the syringomyelia in adolescents with Chiari
      malformation (CM). METHODS: A retrospective review was performed on all CM
      patients between September 2006 and September 2011. A subset of 46 patients,
      including 25 male and 21 female patients, was finally enrolled according to the
      inclusion criteria. The initial age and duration of follow-up averaged 13.9 years
      (range, 10-17 years) and 13 months (range, 6-52 months), respectively. On mid
      sagittal MRI, the following parameters were evaluated pre- and postoperatively
      (follow-up >= 6 months): the longitudinal and transverse position of bulbopontine
      sulcus, the fourth ventricle vertex, the lower extreme of cerebella tonsil, the
      cervico-medullary angle, the maximal syrinx/cord(S/C) ratio and the syrinx
      length. Changes in these parameters were analysed using the paired samples t
      test, and for these reaching statistical significances, an additional bivariate
      correlation analysis was performed to investigate their relation with syrinx
      resolution. RESULTS: At the latest follow-up, upward shifting of the bulbopontine
      sulcus was observed in 31 patients(67.4%), with upward shifting of the lower
      extreme of cerebella tonsil presenting in 35 patients(76.0%). The maximal S/C
      ratio and the syrinx length were significantly improved postoperatively (t =
      7.114 and 7.816, P = 0.000).Significant resolution of the syrinx was demonstrated
      in 40 patients(86.9%), and more specifically, the average improvement rates of
      the maximal S/C ratio and the syrinx length were 32% +/- 30%and 43% +/- 33%,
      respectively. In addition, the bivariate correlation analysis revealed that
      syrinx resolution was significantly correlated with the upward shifting of the
      bulbopontine sulcus (r = 0.332, P = 0.027) and lower extreme of cerebella (r =
      0.298, P = 0.044) . CONCLUSION: The upward shifting of the bulbopontine sulcus
      and the lower extreme of cerebella tonsil might be implicated in the mechanisms
      of postoperative syrinx resolution.

PMID- 24433768
TI  - [Lung cancer associated paraneoplastic limbic encephalitis: an analysis of 7
      cases].
AB  - OBJECTIVE: To analyze the clinical features, diagnosis and treatment of lung
      cancer associated paraneoplastic limbic encephalitis (PLE). METHODS: The clinical
      data of 7 cases of patients with lung cancer associated PLE out of 8927 patients
      of lung cancer from January 2000 to May 2010 was analyzed retrospectively. All
      the patients were male, aging from 41 to 54 years with a mean of 48 years. The
      data including history, physical examination, laboratory tests, diagnosis,
      treatment and follow-up were collected and analyzed. RESULTS: All the 7 patients
      had smoking history. All 7 patients had varying short-term memory loss, 6 had
      epilepsy, 4 had different degrees of mental disorders, and 2 had syndrome of
      inappropriate secretion of antidiuretic hormone. Malignancies were screened and
      detected by chest X-ray or CT scan, while the pathological diagnoses were
      obtained through biopsy or transbronchial needle aspiration through electronic
      bronchoscope (5/7), biopsy of supraclavicular lymph nodes (1/7) and open
      pulmonary lobectomy (1/7). The pathological diagnosis included small cell lung
      cancer in 6 cases, adenocarcinoma of lung in 1 case. During the follow-up, 1
      patient was lost, and the mean time of follow-up of the remaining 6 patients was
      about 11.5 months (ranged from 4 to 21 months). Four patients received early
      immunosuppressive treatment in terms of corticosteroids, only slight relief of
      neurological symptoms was seen in 2 patients. However, after chemotherapy (6/6),
      radiation (3/6), or surgical removal of the tumor (1/6), complete remission (3/6,
      with negative anti-Hu antibody) or partial remission (3/6, 2 of whom with
      positive anti-Hu antibody) of neurological symptoms were observed. Till October
      2010, 3 patients with poorer tumor stag died ( survival were 4, 10, and 14 months
      respectively), while the other 3 patients with negative anti-Hu antibody and
      relative better tumor stag were still in the follow-up (the period were 5, 15,
      and 21 months). CONCLUSIONS: PLE is a rare disease. In comparison with
      immunosuppressive therapy, chemotherapy, radiation or surgical removal of the
      tumor could provide better remission of the neurological symptoms. Positive serum
      anti-Hu antibody, poorer tumor stag, and together with poorer response to
      treatments seem to indicate a poorer prognosis.

PMID- 24433769
TI  - [Correlation analysis between imaging features and lymph node metastasis in T1a
      lung adenocarcinoma].
AB  - OBJECTIVE: To analyze the data of patients with clinical stage T1a lung
      adenocarcinoma and find the predictive factors associated with lymph node
      metastasis. METHODS: From January to June 2012, 271 patients with small nodules
      of peripheral lung adenocarcinoma were enrolled in the retrospective review.
      There were 105 male and 112 female patients, with an average age of (61 +/-
      11)years (range 32-85 years). The data were collected including age, gender,
      smoking history, carcinoembryonic antigen(CEA), imaging findings, surgical
      procedure, pleural involvement, symptoms, tumor size, pathological
      classification, pathologic stage, maximum standardized uptake value(SUVmax) and
      lymph node metastasis. The predictive factors of lymph node metastasis in
      clinical factors were detected by univariate and multivariate analysis. RESULTS:
      By preoperative thin-section CT, 35 patients were categorized as pure ground
      grass opacity(GGO), 11 cases of atypical adenomatous hyperplasia, 24 cases of
      adenocarcinoma in situ, with no lymph node metastasis. Categorized as mixed
      ground-glass opacities in 89 patients, 84 patients (94.4%) had no lymph node
      metastasis, only 5 patients (6.0%) with lymph node metastasis. Categorized as
      solid nodules in 93 patients, a total of 28 cases (30.1%) had lymph node
      metastasis. There were statistically significant difference between three groups
      (chi(2) = 23.41, P < 0.001) . By univariate analysis, we found that the
      predictive factors of lymph node metastasis were as follows: tumor size > 1 cm
      (chi(2) = 9.021, P < 0.003) , imaging performance with mixed GGO or solid nodules
      (chi(2) = 23.41, P < 0.000) , CEA > 5 ug/L (chi(2) = 15.541, P < 0.000) and PET
      CT SUVmax > 5 (chi(2) = 0.644, P < 0.000). By multivariate analysis, we found
      that imaging performance (mixed GGO or solid nodules) was the independent
      predictor of lymph node metastasis in clinical factors (OR = 166.116,
      95%CI:18.161-25.19, P < 0.001) . CONCLUSIONS: Patients of pure GGO generally do
      not have lymph node metastasis. Tumor diameter > 1 cm, imaging findings with the
      mixed GGO or solid nodules, carcinoembryonic antigen CEA > 5 ug/L, PET-CT SUVmax
      > 5 are predictive factors of lymph node metastasis in which imaging is
      independent predictor.

PMID- 24433771
TI  - [Surgical management of intracranial mirror aneurysms].
AB  - OBJECTIVE: To study the clinical characteristics and treatment strategies of
      mirror aneurysms. METHODS: Nineteen patients with 20 pairs of mirror aneurysms
      from November 2007 to November 2012 were retrospectively analysed. Among the 19
      patients, 13 were female and 6 were male, mean age was 56 years (ranged 32-75
      years). Distribution of the lesions included 11 bilateral posterior communicating
      artery aneurysms (one with a pair of anterior choroidal artery aneurysm), 4
      bilateral middle cerebral artery aneurysms, 3 bilateral paraclinoidal aneurysms,
      and 1 bilateral pericallosal-callosomarginal artery aneurysm. Surgical strategies
      were selected according to location of hemorrhage, Hunt-Hess grade, location and
      size of aneurysm, etc. RESULTS: Four mirror aneurysms were clipped at one stage,
      3 mirror aneurysms were clipped at two stages, 2 were treated with combination of
      clipping and coiling and remaining 10 were clipped unilaterally. At discharge, 15
      out of 19 patients had a Glasgow Outcome Scale score of 5, 4 patients had a score
      of 4. The mean clinical follow-up was 18.6 months (range 3-50 months). Two
      patients had oculomotor nerve palsy postoperatively. At 3-month follow-up, 1
      improved and 1 unchanged. In 10 patients with unilateral clipping, contralateral
      aneurysms were unruptured, small ( < 5 mm) and regular. No remnant or recurrence
      of aneurysm were found in other 9 patients whose bilateral aneurysms had been
      treated. CONCLUSIONS: The mirror aneurysms are rare kinds of multiple aneurysms.
      The aneurysm responsible for hemorrhage should be treated with first priority.
      The contralateral unruptured aneurysm could be observed, clipped or coiled in one
      stage, or treated in two separate stages.

PMID- 24433770
TI  - [Recurrence pattern of histological node-negative squamous cell carcinoma of the
      thoracic esophagus after extended radical esophagectomy with lymphadenectomy].
AB  - OBJECTIVE: To analyze the clinical and pathologic influencing factors of early
      recurrence in patients with histological node-negative (pN0 stage) esophageal
      squamous cell carcinoma after radical esophagectomy. METHODS: A retrospective
      study on 112 consecutive pN0 stage esophageal squamous cell carcinoma patients
      who underwent esophagectomy with lymphadenectomy by the same surgical team from
      January 2004 to December 2010. There were 92 male and 20 female patients, aging
      from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards
      model was used to determine the independent risk factors for recurrence within 3
      years after the operation. RESULTS: Recurrence was recognized in 45 patients
      (40.2%) within 3 years after operation. The median time to tumor recurrence was
      17.4 months. Locoregional recurrence was found in 38 patients (33.9%), and
      hematogenous metastasis in 7 patients (6.3%). Recurrence closely correlated with
      tumor location, grade of differentiation, pT stage and pathologic stage (chi(2) =
      6.380 to 18.837, P < 0.05). The Cox multivariate analysis showed that tumor
      location (RR = 1.092, P = 0.049) and pT3-4a stage (RR = 3.296, P = 0.017) were
      independent risk factors for postoperative locoregional recurrence. CONCLUSIONS:
      The most common recurrence pattern of patients with pN0 esophageal squamous cell
      carcinoma would develop recurrence within 3 years after operation is locoregional
      recurrence. Upper/middle thoracic location and pT3-4a stage are independent risk
      factors for locoregional recurrence of pN0 esophageal squamous cell carcinoma
      after operation.

PMID- 24433772
TI  - [Correlation between Gli1 expression and clinicopathological significance in
      human pancreatic cancer].
AB  - OBJECTIVE: To study the clinicopathological significance and relationship of
      Gli1, MDM2 and p53 expression in human pancreatic cancer. METHODS: The expression
      of Gli1, MDM2 and p53 proteins in 57 paired paraffin embedded pancreatic ductal
      adenocarcinoma (PDAC) specimens and adjacent non-cancerous pancreatic tissues was
      detected by immunohistochemistry. The relationship between their expression and
      clinicopathological characters was analyzed. Quantitative real-time PCR (qRT-PCR)
      was used to examine the expression of Gli1 mRNA level in 14 paired fresh PDAC
      specimens and adjacent non-cancerous pancreatic tissues. siRNA interference were
      used to further detect the close relationship among them. RESULTS: IHC showed the
      expression of Gli1 (50.9%), MDM2 (57.9%) and p53 (56.1%) was increased in 57
      cases of pancreatic cancer compared to that in paired normal pancreatic tissues
      (33.3%, 26.3% and 17.5% respectively, t = 2.413, 2.848 and 2.960, all P < 0.05).
      Gli1 expression was positively associated with tumor TNM stage (chi(2) = 8.211, P
      = 0.004), invasion depth (chi(2) = 4.247, P = 0.039) and MDM2 expression (r =
      0.299, chi(2) = 5.105, P = 0.024), while expression of MDM2 and p53 was
      associated with tumor invasion depth (chi(2) = 5.182, P = 0.023) and TNM stage
      (chi(2) = 5.696, P = 0.017), respectively. Univariate and multivariate analysis
      revealed that Gli1 was an independent adverse prognostic indicator for patients
      with PDAC (RR = 2.290, 95%CI: 1.051-4.992, P = 0.037), and patients with Gli1 and
      MDM2 co-expression had a significantly poorer overall survival than patients with
      their negative expression (P = 0.034). Gli1 mRNA expression was much higher in 14
      cases of PDAC than that in adjacent normal pancreatic tissues (t = 2.926, P =
      0.012). In p53 mutant AsPC-1 cells, Gli1 knockdown down regulated MDM2, but had
      no effect on p53 expression, whereas Gli1 knockdown down regulated MDM2 and up
      regulated p53 protein levels in p53 wild-type Capan-2 cells. CONCLUSIONS: Gli1,
      MDM2 and p53 are overexpressed in PDAC, and are benefit for predicting patients'
      prognosis. Gli1can regulate MDM2 and wild-type p53 expression. Their co
      expression might coordinately contribute to the development and progression of
      PDAC.

PMID- 24433773
TI  - [Prophylatic antibiotic use in percutaneous nephrolithotomy: a meta-analysis].
AB  - OBJECTIVE: To determine whether antibiotic prophylaxis can reduce the risk of
      postoperative infective complications in patients undergoing percutaneous
      nephrolithotomy (PCNL) who have sterile preoperative urine. METHODS: MEDLINE,
      EMBASE, Cochrane Collaboration Reviews, CMCC and CNKI were searched for RCTs
      comparing antibiotic prophylaxis with placebo (or blank controls) for patients
      undergoing PCNL with preoperative sterile urine. The search strategy was made
      according to the Collaborative Review Group search strategy. Data were extracted
      by 2 reviewers using the designed extraction form. The software RevMan 4.2 was
      used to review management and data analysis. RESULTS: A total of 9 trails, 1
      placebo controlled, 3 non treatment controlled, and 5 active controlled,
      involving 1018 patients, met the inclusion criteria. Prophylactic antibiotic use
      in patients at low risk undergoing PCNL significantly decreased fever (RR = 0.71,
      95% CI: 0.54-0.92, P = 0.009), bacteriuria (RR = 0.39, 95%CI: 0.23-0.67, P =
      0.0006) and bacteremia incidence (RR = 0.43, 95%CI: 0.25-0.73, P = 0.002).
      Effective antibiotic classes included quinolone which significantly decreased
      bacteriuria incidence (RR = 0.31, 95%CI: 0.12-0.82, P = 0.010) and nitrofurantoin
      which significantly decreased fever incidence (RR = 0.38, 95%CI: 0.24-0.61, P =
      0.005). Extended course significantly decreased fever incidence (RR = 0.64,
      95%CI: 0.47-0.87, P = 0.004) and bacteriuria incidence (RR = 0.35, 95%CI: 0.18
      0.71, P = 0.003). CONCLUSIONS: Prophylactic antibiotics can significantly
      decrease the incidence of postoperative infective complications. A significant
      decrease in bacteriuria incidence can be achieved with quinolones. Extended
      course is effective in decreasing fever, and bacteriuria incidence.

PMID- 24433774
TI  - Among 1,706 cases of abdominal wall reconstruction, what factors influence the
      occurrence of major operative complications?
AB  - BACKGROUND: Abdominal wall reconstruction (AWR) poses a substantial operative
      challenge, often in the setting of multiple failed attempts at repair in high
      risk patients. Our aim was to assess risk factors for major operative morbidity
      after AWR using the American College of Surgeons-National Surgical Quality
      Improvement Program (ACS-NSQIP) patient database. METHODS: A review of the ACS
      NSQIP database of outcomes from 2005 to 2010 was performed to identify patients
      undergoing AWR utilizing Current Procedural Terminology codes for ventral hernia
      repair and a concomitant component separation. Independent variables included
      patient demographics, medical comorbidities, and operative considerations. Major
      operative complication (deep wound infection, graft or prosthetic loss, or
      unplanned return to the operating room within 30 days) was used as our dependent
      variable. Stepwise, multivariate logistic regression was performed to evaluate
      patient risk factors influencing the occurrence of major operative complications.
      RESULTS: We identified 1,706 patients with an average age of 55.9 +/- 12.8 years
      with 30.1% undergoing concurrent intra-abdominal procedures and 57.1% undergoing
      mesh repair. Notable medical comorbidities included obesity (63.4%), smoking
      (24.9%), hypertension (53.1%), diabetes (19.9%), and anemia (22.6%). Average
      operative time was 211.7 +/- 105.0 minutes. Regression analysis determined that
      prolonged operative time (odds ratio [OR], 2.7; P < .001) and American Society of
      Anesthesiologists >2 (OR, 1.8; P = .009) were positively associated, whereas
      advanced age (OR, 0.5; P = .005) was negatively associated with the occurrence of
      major operative complications. CONCLUSION: Greater operative times and overall
      patient health are important prognostic factors for individuals undergoing AWR.
      The increased physiologic stress of a greater operative duration on patients who
      often have multiple comorbidities seems to play a significant role in predicting
      negative outcomes after AWR.

PMID- 24433775
TI  - Is there an evidence-based argument for embracing an antimicrobial (triclosan)
      coated suture technology to reduce the risk for surgical-site infections? A meta
      analysis.

PMID- 24433776
TI  - National estimates of noncanine bite and sting injuries treated in US Hospital
      Emergency Departments, 2001-2010.
AB  - OBJECTIVE: Injuries resulting from contact with animals and insects are a
      significant public health concern. This study quantifies nonfatal bite and sting
      injuries by noncanine sources using data from the National Electronic Injury
      Surveillance System-All Injury Program (NEISS-AIP). METHODS: The NEISS-AIP is an
      ongoing nationally representative surveillance system used to monitor all types
      and causes of injuries treated in US hospital emergency departments (EDs). Cases
      were coded by trained hospital coders using information from medical records on
      animal and insect sources of bite and sting injuries being treated. Data were
      weighted to produce national annualized estimates, percentages, and rates based
      on the US population. RESULTS: From 2001 to 2010 an estimated 10.1 million people
      visited EDs for noncanine bite and sting injuries, based on an unweighted case
      count of 169,010. This translates to a rate of 340.1 per 100,000 people (95% CI,
      232.9-447.3). Insects accounted for 67.5% (95% CI, 45.8-89.2) of bite and sting
      injuries, followed by arachnids 20.8% (95% CI, 13.8-27.9). The estimated number
      of ED visits for bedbug bite injuries increased more than 7-fold-from 2156 visits
      in 2007 to 15,945 visits in 2010. CONCLUSIONS: This study provides an update of
      national estimates of noncanine bite and sting injuries and describes the
      diversity of animal exposures based on a national sample of EDs. Treatment of
      nonfatal bite and sting injuries are costly to society. Direct medical and work
      time lost translates to an estimated $7.5 billion annually.

PMID- 24433777
TI  - Appalachian Trail hikers' ability to recognize Lyme disease by visual stimulus
      photographs.
AB  - BACKGROUND: Lyme disease is the most common vector-borne infectious disease in
      North America. With nearly 2,500 Appalachian Trail (AT) hikers entering the
      endemic area for as long as 6 months, exposure to the disease is likely. The
      characteristic exanthem of erythema migrans (EM) should be a trigger for seeking
      medical treatment, and its recognition in this relatively isolated environment is
      important. OBJECTIVE: The purpose of this study was to determine the ability of
      AT hikers to identify EM, the exanthem of Lyme disease. METHODS: Hikers were
      administered a photographic stimulus in this Internal Review Board-approved pilot
      study. Historical hiking data, basic demographics, and self-reported treatment
      and diagnosis were collected. RESULTS: In all, 379 responses were collected by 4
      researchers at 3 geographically separate locations at or proximate to the AT from
      June 2011 to May 2012. Fifty-four percent of respondents (206 of 379) were able
      to recognize the photographs of EM/Lyme disease; 46% could not. Of those who did
      recognize EM, 23 (6%) had seen it either on themselves or on another hiker while
      on the AT. A total of 37 hikers stated that they had been diagnosed with Lyme
      disease while hiking, and of these, 89% were treated with antibiotics. Thirteen
      of these 37 hikers (35%) diagnosed with Lyme disease had visualized an embedded
      tick. Nine percent of all respondents reported they had been diagnosed with Lyme
      disease by a healthcare practitioner, whether from EM, symptomatology, or by
      titer. CONCLUSIONS: This study suggests that hikers are poorly able to recognize
      the characteristic exanthem of Lyme disease but have a high exposure risk.

PMID- 24433778
TI  - Tolerance of anemia: understanding the adaptive physiological mechanisms which
      promote survival.
AB  - Acute anemia and hemodilution are associated with increased organ injury (brain,
      kidney) and mortality in patients undergoing surgery. A more complete
      understanding of the adaptive physiological mechanisms which maintain tissue
      oxygen delivery, and the hemoglobin concentration at which these mechanisms are
      overwhelmed, would help to direct treatments to improve event free survival in
      patients who experience acute anemia. Adaptive cardiovascular and cellular
      responses are key to maintaining survival during acute anemia. We have identified
      neuronal nitric oxide synthase (nNOS) and hypoxia inducible factor (HIF) promote
      survival during acute anemia in animal models. In addition, activation of tissue
      nNOS may promote oxidation of hemoglobin to methemoglobin: a potential biomarker
      of anemia-induced tissue hypoxia. We continue to explore the possibility that
      methemoglobin, and other hypoxic signaling molecules, may be biomarkers of anemia
      induced tissue hypoxia which can be used to guide optimal treatment of anemic
      patents. 

PMID- 24433779
TI  - Influence of L-arginine supplementation on reproductive blood flow and embryo
      recovery rates in mares.
AB  - Supplementation with L-arginine can increase uterine arterial blood flow and
      vascular perfusion of the preovulatory follicle in mares. Increased vascular
      perfusion of the preovulatory follicle has been correlated with successful
      pregnancy in mares. The objective of this study was to determine if supplemental
      L-arginine would increase ovarian arterial blood flow, vascular perfusion of the
      preovulatory follicle, and embryo recovery rates in mares. Mares were blocked by
      age and breed and assigned at random within block to L-arginine supplementation
      or control groups. Mares were fed L-arginine beginning 17 days before and through
      the duration of the study. Transrectal Doppler ultrasonography was used to
      measure ovarian arterial blood flow and vascular perfusion of the preovulatory
      follicle daily when it reached 35 mm and subsequent CL on Days 2, 4, and 6.
      Mares, on achieving a follicle of 35 mm or more were bred via artificial
      insemination and an embryo collection was attempted 7 days after ovulation.
      Treatment did not affect interovulatory interval (arginine-treated, 18.1 +/- 2.6
      days; control, 20.7 +/- 2.3 days) or embryo recovery rate (arginine-treated, 54%;
      control, 48%). Mares treated with l-arginine had a larger follicle for the 10
      days preceding ovulation than control mares (30.4 +/- 1.2 and 26.3 +/- 1.3 mm,
      respectively; P < 0.05) and vascular perfusion of the dominant follicle tended (P
      = 0.10) to be greater for the 4 days before ovulation. No differences were
      observed between groups in diameter or vascular perfusion of the CL. Resistance
      indices, normalized to ovulation, were not significantly different between groups
      during the follicular or luteal phase. Oral l-arginine supplementation increased
      the size and tended to increase perfusion of the follicle 1, but had no effect on
      luteal perfusion or embryo recovery rates in mares.

PMID- 24433780
TI  - Inhibition of beta-N-acetylglucosaminidase by acetamide affects sperm motility
      and fertilization success of rainbow trout (Oncorhynchus mykiss) and Siberian
      sturgeon (Acipenser baerii).
AB  - beta-N-Acetylglucosaminidase (beta-NAGase) is an enzyme found in the sperm
      acrosome of numerous animal species including fish. Fish spermatozoa differ in
      their morphology including acrosome or acrosomeless aquasperm in chondrostean
      (e.g., sturgeon) and teleostean (e.g., rainbow trout). It has been shown that
      beta-NAGase exists with high activity in both eggs and sperm of these species.
      The present study shows the potency of beta-NAGase in fertilization. In rainbow
      trout, increase in sperm motility parameters (VAP and MOT) were observed in the
      presence of acetamide, an inhibitor for beta-NAGase. In contrast, sperm motility
      parameters (VCL, VSL, VAP, MOT, and PRG) were reduced on the Siberian sturgeon in
      the presence of acetamide. The inhibition of the activity of beta-NAGase in
      rainbow trout spermatozoa was led to a reduction in the number of fertilized eggs
      from 79% to 40%, whereas in sturgeon no change was observed in fertilization.
      Moreover, inhibition of beta-NAGase in both spermatozoa and eggs of trout and
      sturgeon resulted in significant decrease in fertilization rate from 79% to 1% in
      rainbow trout and from 84% to 12% in Siberian sturgeon. Our research proves that
      beta-NAGase can play a significant role in the fertilization process in
      teleosteans. 

PMID- 24433781
TI  - Comparative metabolism of PGFM (13,14-dihydro-15-keto-PGF2alpha) in feces of
      felids.
AB  - Methods for monitoring endocrine activities are useful tools for reproduction
      management. In particular, captive breeding of endangered felid species is
      considered to be an important part of the species conservation efforts. Within
      breeding programs, reliable methods for pregnancy diagnosis are highly demanded
      to prevent peri- and postpartal losses, but pregnancy diagnosis based on gestagen
      metabolites in felids is hampered by pseudopregnancies. Recently, we described
      fecal PGFM as an indicator for pregnancy in several feline species, but peak
      levels of PGFM secretion differed dramatically between species. It is believed
      that prostaglandin composition and metabolism pathways may differ as well.
      Therefore, a study was devised to both compare various fecal immunoreactive PGFM
      metabolites and to identify prostaglandins in fecal extracts by liquid
      chromatography-mass spectrometry (LCMS). Our results confirmed that fecal
      metabolite patterns differ between feline species. The identity of PGFM was
      confirmed in six of eight felids. In Iberian lynx and the Sumatran tiger, PGFM
      did not exceed 5% of all immunoreactivities. The total number of
      immunoreactivities varied between two (e.g., domestic cat) and four (e.g.,
      oncilla). Several prostaglandins were identified by LCMS; apart from PGFM, all
      LCMS-identified prostaglandins, including tetranor-PGFM, did not show any cross
      reactivity with our PGFM-specific antibody. This indicates the existence of still
      unknown eicosanoids and further studies are needed to clarify the origin of the
      different metabolites. Although differing stages of pregnancy did not reveal
      significant differences in the composition of metabolites, we could not exclude
      the possibility that metabolites from other prostaglandins (e.g. PGE2)
      contributed to the fecal metabolite patterns. 

PMID- 24433782
TI  - Results of endovascular repair of infrarenal aortic aneurysms using the Endurant
      stent graft.
AB  - OBJECTIVE: Recent reports showed that the Endurant stent graft (Medtronic
      Cardiovascular, Santa Rosa, Calif) is safe and effective for endovascular repair
      of abdominal aortic aneurysms (AAAs). However, due to its relatively recent
      introduction, only short-term follow-up data are available. This study presents
      the 4-year results using this device. METHODS: All clinical data, including
      detailed anatomic information of the first 100 consecutive patients treated with
      the Endurant stent graft for an infrarenal AAA in three Dutch high-volume
      hospitals, were prospectively collected. Computed tomography angiography was
      routinely performed before the procedure, <= 1 month, and at 1 year post
      endovascular aneurysm repair. Thereafter, the imaging modality during yearly
      follow-up was individualized (duplex ultrasound imaging or computed tomography
      angiography). Patients were classified as within or outside the instructions for
      use (IFU) for analysis. Study end points were primary clinical success, overall
      and AAA-related mortality, and sac morphology changes and endoleak during follow
      up. Estimates were obtained using Kaplan-Meier plots. RESULTS: The study included
      100 consecutive patients (88 men) with a median age of 74 years (interquartile
      range [IQR], 67-79 years) and median AAA diameter of 58 mm (IQR, 55-65 mm),
      between December 2007 and March 2009. Twenty patients (20%) were treated outside
      the IFU (18, outside proximal neck IFU, one outside iliac IFU, and one outside
      both IFUs). Median follow-up was 48 months (IQR, 36-53 months), and no patients
      were lost. One contained rupture was observed after 1.5 months due to graft
      infection. No patients had graft migration. Two type Ia endoleaks, 5 type Ib
      endoleaks, and 15 type II endoleaks were found. Primary clinical success was 97%,
      90%, 84% and 77% at 1, 2, 3, and 4 years, respectively. Primary clinical success
      was comparable for patients treated within or outside IFU (P = .20), although
      both patients outside iliac IFU needed a secondary iliac intervention. Over time,
      maximum aneurysm diameter decreased >= 5 mm, remained stable, and increased >= 5
      mm in 58%, 32%, and 10% of the patients, respectively. All-cause mortality was
      20% at 4 years, with a 3% AAA-related mortality. CONCLUSIONS: The 4-year follow
      up data of the Endurant stent graft for AAA treatment shows its use results in a
      low AAA-related mortality with adequate prevention of rupture or aneurysm growth.
      Although patients with very challenging anatomy were treated in our series,
      primary clinical success rates were comparable for patients treated within and
      outside the IFU. However, both patients outside the iliac IFU needed a secondary
      iliac intervention. The knowledge of the present results may aid in improving
      outcomes in the future.

PMID- 24433783
TI  - Endovascular strategies for treatment of embolizing thoracoabdominal aortic
      lesions.
AB  - OBJECTIVE: Aortic sources of peripheral and visceral embolization remain
      challenging to treat. The safety of stent graft coverage continues to be debated.
      This study reports the outcomes of stent coverage of these complex lesions.
      METHODS: Hospital records were retrospectively reviewed for patients undergoing
      aortic stenting between 2006 and 2013 for visceral and peripheral embolic
      disease. Renal function, method of coverage, and mortality after stent grafting
      were reviewed. RESULTS: Twenty-five cases of embolizing aortic lesions treated
      with an endovascular approach were identified. The mean age was 65 +/- 13 years
      (range, 45-87 years), and 64% were female. Sixteen (64%) patients presented with
      peripheral embolic events, six with concomitant renal embolization. Five patients
      presented with abdominal or flank pain, and two were discovered incidentally.
      Three patients had undergone an endovascular procedure for other indications
      within the preceding 6 months of presentation. Nineteen patients had existing
      chronic kidney disease (stage II or higher), but only three had stage IV disease.
      Of the eight patients tested, four had a diagnosed hypercoagulable state. Eight
      of the patients had lesions identified in multiple aortic segments, and aortic
      aneurysm disease was present in 24%. Coverage of both abdominal and thoracic
      sources occurred in eight patients, whereas 17 had only one segment covered.
      Minimal intraluminal catheter and wire manipulation was paired with the use of
      intravascular ultrasound in an effort to reduce embolization and contrast use.
      Intravascular ultrasound was used in the majority of cases and transesophageal
      echo in 28% of patients. Two patients with stage IV kidney disease became
      dialysis-dependent within 3 months of the procedure. No other patients had an
      increase in their postoperative or predischarge serum creatinine levels. No
      embolic events were precipitated during the procedure, nor were there any
      recurrent embolic events detected on follow-up. The 1-year mortality rate was
      25%. CONCLUSIONS: Endovascular coverage of atheroembolic sources in the aorta is
      feasible and is safe and effective in properly selected patients. It does not
      appear to worsen renal function when performed with the use of specific technical
      strategies.

PMID- 24433784
TI  - Biocontrol potential of essential oil monoterpenes against housefly, Musca
      domestica (Diptera: Muscidae).
AB  - Housefly (Musca domestica L.), one of the most common insects in human
      settlements, has been associated as vectors for various food-borne pathogens,
      causing food spoilage and disease transmission. The control of housefly was
      attempted using plant monoterpenes; menthone, menthol, menthyl acetate, limonene,
      citral and 1,8-cineole, against different life stages of housefly. Bioefficacy
      against housefly adults revealed highest repellent activity by menthol (95.6
      percent) and menthone (83.3 percent). Against housefly larvae, menthol with an
      LC90 of 0.02 ul/cm(2) in contact toxicity assay and menthone with a LC90 value of
      5.4 ul/L in fumigation assay were found to be most effective control agent. With
      respect to pupicidal activity, superior performance was shown by menthol, citral
      and 1,8-cineole in contact toxicity assay and citral and 1,8-cineole in
      fumigation assay. Limonene was found to be the poorest performer in all the
      assays. Overall, highest efficacy observed for menthol and menthone in various
      bioassays was in agreement with the results of essential oil activity obtained
      previously. Significant activity of monoterpenes against various life stages of
      housefly demonstrates their potential as excellent insecticides with prospects of
      monoterpenes being developed into eco-friendly and acceptable products for
      housefly control.

PMID- 24433785
TI  - Genotoxic and biochemical effects of atrazine and Roundup((r)), alone and in
      combination, on the Asian clam Corbicula fluminea.
AB  - The present study aimed to evaluate biochemical and genotoxic effects of the
      herbicides atrazine (ATZ) and Roundup((r)) (RD) separately, as well as their
      mixture, on the freshwater clam Corbicula fluminea after 96 h exposure. Animals
      were exposed to 2 and 10 ppb of ATZ (ATZ2 and ATZ10), 2 and 10 ppm of RD (RD2 and
      RD10) and the following mixtures: 2 ppb ATZ+2ppm RD (AR2) and 10 ppb ATZ+10 ppm
      RD (AR10). Activities of ethoxyresorufin-O-deethylase (EROD), glutathione-S
      transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx) and glutathione reductase (GR), as well as the multixenobiotic
      resistance mechanism (MXR), reduced glutathione concentrations (GSH) and lipid
      peroxidation (LPO) were measured in gills and digestive gland. DNA damage was
      determined in clams hemocytes through the comet assay. The gills were more
      susceptible to the action of the herbicides and the results showed that ATZ2 and
      ATZ10 caused a significant reduction in EROD and the mixture leads to a
      significant decrease in EROD and MXR. No significant change in the
      biotransformation parameters was observed in the digestive gland. Regarding the
      primary antioxidant defenses, SOD activity increased in the gills of clams
      exposed to ATZ10 and RD10 and in the digestive gland of animals exposed to RD2
      and RD10, CAT activity was significantly reduced only in digestive gland of clams
      exposed RD10 while GPX increased in the gills after exposure to ATZ2 and RD10.
      The exposure to RD10 caused a significant increase in LPO in both gills and
      digestive gland. While the exposure to ATZ and RD separately did not increase DNA
      damage, the exposure to AR2 and AR10 caused a significant increase in the
      occurrence of DNA damage. In conclusion, this study showed that both herbicides
      applied alone caused effects on C. fluminea; ATZ interfered mostly in
      biotransformation while RD interfered mainly in antioxidant defenses leading to
      lipid peroxidation. The herbicides mixture showed antagonistic effects on the
      gills EROD and on lipid peroxidation in gills and digestive gland and synergistic
      effects on the gills MXR and on DNA damage in the hemocytes.

PMID- 24433786
TI  - Proteomic analysis in caged Mediterranean crab (Carcinus maenas) and chemical
      contaminant exposure in Teboulba Harbour, Tunisia.
AB  - This study uses proteomics approach to assess the toxic effects of contaminants
      in the Mediterranean crab (Carcinus maenas) after transplantation into Teboulba
      fishing harbour. High levels of aliphatic and aromatic hydrocarbons were detected
      in sediments. Although their effects on vertebrates are well described, little is
      known about their early biological effects in marine invertebrates under
      realistic conditions. Protein expression profiles of crabs caged for 15, 30 and
      60 days were compared to unexposed animals. Nineteen proteins with significant
      expression differences were identified by capLC-uESI-IT MS/MS and homology search
      on databases. Differentially expressed proteins were assigned to five different
      categories of biological function including: (1) chitin catabolism, (2)
      proteolysis, (3) exoskeleton biosynthesis, (4) protein folding and stress
      response, and (5) transport. The proteins showing major expression changes in C.
      maenas after different caging times may be considered as novel molecular
      biomarkers for effectively biomonitoring aquatic environment contamination. 

PMID- 24433787
TI  - Screening for PCDD/Fs and dl-PCBs in local and imported food and feed products
      available across the State of Kuwait and assessment of dietary intake.
AB  - A total of 318 local and imported meat, milk, eggs, fish, and animal feed samples
      collected in Kuwait were analyzed by cell-based reporter gene assay (Dioxin
      Responsive Chemical Activated LUciferase gene eXpression DR-CALUX) for PCDD/Fs
      and dl-PCBs. The bioanalytical equivalents (BEQs) obtained by DR-CALUX bioassay
      were compared with the official maximum limits according to the European
      Commission (EC) regulations. Suspected and randomly chosen negative samples were
      analyzed by gas chromatography-high resolution mass spectrometry (GC-HRMS). The
      results showed that among suspected samples, one sample was confirmed to be non
      compliant. The positive sample was of imported origin. The correlation
      coefficient of 0.98 between DR-CALUX and GC-HRMS was found. Moreover, the average
      daily intakes of PCDD/Fs and dl-PCBs for the Kuwaiti population were estimated.
      Results obtained in this study were discussed and compared with other published
      data. 

PMID- 24433788
TI  - Gastrointestinal absorption, dynamic tissue-specific accumulation, and isomer
      composition of dechlorane plus and related analogs in common carp by dietary
      exposure.
AB  - Dechlorane plus (DP) is a high-productive volume substance which had been
      identified as ubiquitous pollutant and has been widely detected in biota. In the
      present study, common carp (Cyprinus carpio) was exposed to known amounts of
      commercial DP-25 under laboratory conditions. The gastrointestinal absorption and
      tissue-specific bioaccumulation of DP and its dechlorinated analogs in common
      carp were investigated. The higher absorption efficiencies but lower assimilation
      efficiencies of anti-isomers indicated stereoselective metabolism of anti-isomers
      in fish. Linear uptake curves were seen in serum and muscle, but the depuration
      curves for all the four tissues (muscle, serum, liver and gonad) did not follow
      the first-order kinetics. The liver exhibited a high affinity for anti-isomers
      during the experiment. Other tissues, such as serum, muscle, and gonad, showed a
      selective accumulation of syn-DP in the early stages of the experiment,
      particularly the serum. However, the deviation of fanti between different tissues
      disappeared at late stages of the experiment, and the fanti values in all tissues
      were close to that in commercial mixtures. Our results suggest that the
      bioaccumulation of DP is a complex and multi-factorial process. 

PMID- 24433789
TI  - Characterization of plasma cholinesterase in rabbit and evaluation of the
      inhibitory potential of diazinon.
AB  - Several studies indicate that more than one cholinesterase form may be present in
      the blood of mammals. In this study the predominant plasma cholinesterase
      activity, the physiological cholinesterase activity as well as cholinesterase sex
      dependent changes in non-exposed individuals of rabbit have been established.
      Plasma cholinesterase was characterized using three substrates (acetylthiocholine
      iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three
      cholinesterase inhibitors (eserine sulfate, BW284C51 and iso-OMPA). The results
      indicated that propionylthiocholine was the preferred substrate by plasma
      cholinesterase followed by acetylthiocholine and butyrylthiocholine, and the
      predominant enzymatic activity was acetylcholinesterase. Physiological plasma
      cholinesterase activity was 198.9 +/- 5.8 nmol/min/ml for male and 205.2 +/- 5.0
      nmol/min/ml for female using acetylthiocholine as substrate. Thus, sex had no
      significant effect on the physiological cholinesterase activity (p>0.05). In
      addition, the in vivo and in vitro sensitivity of plasma cholinesterase to
      diazinon was also investigated. In rabbits exposed to single doses of diazinon
      (25 or 125 mg/kg) the higher inhibitions of plasma cholinesterase were reached 9h
      after oral administration (53% and 87% inhibition, respectively). Cholinesterase
      activity significantly recovered up to values similar to pre-administration
      between 3 and 7d depending on the administered dose and sex of the animals.
      Plasma cholinesterase activity decreased to 24%, 53% and 74% of the initial
      activity at 9h of in vitro exposure to 1.25, 3.13 and 6.25mg/l of diazinon,
      respectively, and it remained steadily depressed throughout the experimental
      period (10d). This study has demonstrated the sensitivity of cholinesterase
      activity in plasma of rabbits following both in vivo and in vitro exposure to sub
      lethal concentrations of diazinon.

PMID- 24433790
TI  - Solid phase microextraction of organic pollutants from natural and artificial
      soils and comparison with bioaccumulation in earthworms.
AB  - The presented study investigates the use of passive sampling, i.e. solid phase
      microextraction with polydimethylsiloxane fibers (PDMS-SPME), to assess the
      bioavailability of fiver neutral organic chemicals (phenanthrene, pyrene,
      lindane, p,p'-DDT, and PCB 153) spiked to natural and artificial soils after
      different aging times. Contaminant bioavailability was assessed by comparing PDMS
      concentrations with results from a 10 day bioaccumulation test with earthworms
      (Eisenia fetida). The hypotheses tested were (i) organic carbon (OC)
      normalization, which is commonly used to account for sorption and bioavailability
      of hydrophobic organic chemicals in soil risk assessment, has limitations due to
      differences in sorptive properties of OC and aging processes (i.e. sequestration
      and biodegradation) and (ii) PDMS-SPME provides a more reliable measure of soil
      contaminant bioavailability than OC normalized soil concentrations. The above
      stated hypotheses were confirmed since the results showed that: (i) the PDMS/soil
      organic carbon partition ratio (R) accounting for the role that OC plays in
      partitioning significantly differed between soils and aging times and (ii) the
      correlation with earthworm concentrations was better using porewater
      concentrations derived from PDMS concentrations than when organic normalized soil
      concentrations were used. Capsule: Sorption of organic compounds measured by SPME
      method and their bioavailability to earthworms cannot be reliably predicted using
      OC content. 

PMID- 24433791
TI  - Heavy metals in Australian grown and imported rice and vegetables on sale in
      Australia: health hazard.
AB  - Dietary exposure to heavy metals is a matter of concern for human health risk
      through the consumption of rice, vegetables and other major foodstuffs. In the
      present study, we investigated concentrations of cadmium (Cd), cobalt (Co),
      chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn)
      in Australian grown and imported rice and vegetables on sale in Australia. The
      mean concentrations of Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn in Australian grown
      rice were 7.5 ug kg(-1), 21 ug kg(-1), 144 ug kg(-1), 2.9 mg kg(-1), 24.4 mg kg(
      1), 166 ug kg(-1), 375 ug kg(-1), and 17.1 mg kg(-1) dry weight (d. wt.),
      respectively. Except Cd, heavy metal concentrations in Australian grown rice were
      higher than Bangladeshi rice on sale in Australia. However, the concentrations of
      Cd, Cr, Cu, and Ni in Indian rice on sale in Australia were higher than
      Australian grown rice. The concentrations of Cu and Ni in Vietnamese rice, and
      that of Cd, Cr, Cu, Ni, and Pb in Thai rice on sale in Australia were also higher
      than Australian grown rice. Heavy metal concentrations in Pakistani rice on sale
      in Australia were substantially lower than that in Australian grown rice. In
      Australian grown rice varieties, the concentrations of heavy metals were
      considerably higher in brown rice varieties than white rice varieties, indicating
      Australian brown rice as a potential source of dietary heavy metals for
      Australian consumers. The mean concentrations of heavy metals in Australian grown
      and Bangladeshi vegetables on sale in Australia were also determined. Some of the
      Australian grown and Bangladeshi vegetables contained heavy metals higher than
      Australian standard maximum limits indicating them as potential sources of
      dietary heavy metals for Australian consumers. Further investigation is required
      to estimate health risks of heavy metals from rice and vegetables consumption for
      Australian consumers.

PMID- 24433792
TI  - Benthic macroalgae as biological indicators of heavy metal pollution in the
      marine environments: a biomonitoring approach for pollution assessment.
AB  - Metal pollution in the marine coastline environment is an important topical issue
      in the context of ecological disturbance and climate change. Heavy metal
      contaminations (Cd, Cr, Cu, Mn, Ni, Pb and Zn) in seawater and surficial
      sediments, as well as macroalgal diversity, were determined in six different
      locations along the coast of the Gulf of Kutch in India. The marine coastline
      environment was found to be enriched with Cd and Zn in comparison to other
      metals. Significant (p <= 0.05) inter-elemental positive-correlations were
      observed between Fe-Mn, Fe-Cu, Fe-Cr, Fe-Zn, Cr-Cu, Cu-Mn, and Cd-Zn, as well as
      negative-correlations between Cd-Pb, Ni-Pb, and Zn-Pb. Though genus specific
      macroalgal responses to heavy metal accumulation were significant, species
      specific response was insignificant (p <= 0.05). The relative abundance of metals
      in macroalgae followed the order of Fe>Zn>Mn>Cu>Cd>Cr>Ni>Pb. The high uptake of
      metals in green algae (Ulva lactuca and Enteromorpha intestinalis) and brown
      algae (Padina gymnospora and Dictyota bartayresiana) suggested that these algae
      may be used as potential biomonitors for heavy metal pollution. Three pollution
      indicators, Contamination Factor (CF), Enrichment Factor (EF) and Geochemical
      Index (Igeo) were calculated to determine the degree of metal pollution in the
      marine coastline and the contribution of anthropogenic influence.

PMID- 24433793
TI  - A novel Moringa oleifera leaf extract can mitigate the stress effects of salinity
      and cadmium in bean (Phaseolus vulgaris L.) plants.
AB  - Phaseolus vulgaris plants were grown in the presence of NaCl and/or CdCl2
      beginning from the second week, sprayed twice with moringa leaf extract (MLE) at
      21 and 28 days after sowing (DAS), and were sampled at 35 DAS for growth and
      chemical analyses and yielded at the end of experiment. Growth traits, level of
      photosynthetic pigments, green pod yield and pod protein were significantly
      reduced with exposing the plants to NaCl and/or CdCl2. However, the follow up
      foliar application with MLE detoxified the stress generated by NaCl and/or CdCl2
      and significantly enhanced the aforementioned parameters. Either individual or
      combined used stresses increased the electrolyte leakage (EL), lipid peroxidation
      and plant Cd(2+) content, and decreased the membrane stability index (MSI) and
      relative water content (RWC). However, the foliar application of MLE in the
      absence of the stress improved the MSI and RWC and minimized plant Cd(2+) content
      but could not affect EL and lipid peroxidation. Proline content and the activity
      of antioxidant enzymes showed a significant increase in response to MLE as well
      as to NaCl and/or CdCl2 stress. 

PMID- 24433794
TI  - A method for real-time measurement of respiratory rhythms in medaka (Oryzias
      latipes) using computer vision for water quality monitoring.
AB  - The respiratory rhythms of Japanese medaka is considered to be an efficient
      indicator for monitoring water quality since they are sensitive to chemicals and
      can be measured directly from the movement of fish gill tissue generated by their
      breathe. However, few methods have been established to measure the feature of
      small free-swimming fish intuitively. In this article, a method is proposed to
      measure the influence of the pollution to the Japanese medaka's respiratory
      rhythms with computer vision technology in real time. In order to get the images
      which contains the complete gill tissue remotely and steadily, a special object
      container and an experiment platform are designed. With the aim of capturing
      Japanese medaka's respiratory rhythms in real time, a set of image processing
      algorithms such as the color distribution table, Support Vector Machine (SVM),
      adaptive boosting (Adaboost) and mathematical morphology are applied. Then, in
      order to verify the effectiveness and accuracy of the whole method, fourteen
      groups of Japanese medakas are respectively exposed to copper ions solutions with
      different concentrations of 0, 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 mg/L for 48 h. The
      comparison between the human eyes observation and the above method indicates that
      the data obtained through the method is generally accurate. We found that the
      respiratory rate of Japanese medaka showed a downward trend initially when
      exposed in the copper ions solution, afterwards fluctuated repeatly arounding the
      lower rate, before death, the respiratory rate rised slowly for a while. With the
      increase of concentration, this trend will be more obvious. But the above
      phenomenon is absolutely different from that in the standard dilution water.
      Moreover, the two kinds of special respiratory rhythm of medakas poisoning were
      discovered. This method can be widely applied to study some toxic substances'
      effects on Japanese medaka's respiratory rhythms and to assess the degree of risk
      of the water environment.

PMID- 24433795
TI  - Mercury and selenium intake by seafood from the Ionian Sea: A risk evaluation.
AB  - The subject of the present study is the evaluation of the concentrations of
      mercury (Hg) and selenium (Se) in fish and shellfish from the Gulf of Catania
      (Ionian Sea) and the assessment of related risk-based consumption limits per
      single contaminant in adults and children. In contrast to the potential harm from
      Hg, Se is an essential element that is normally found in high levels in seafood.
      If the amount of Hg is high enough, it could bind Se and irreversibly inhibit
      selenium-dependent enzymes. Thus, adequate levels of Se need to be available to
      replace the amount of Se lost to Hg sequestration, thereby maintaining normal
      selenoprotein synthesis. Hg analysis was conducted using a flow injection
      analysis system coupled with an atomic adsorption spectrometer, and Se analysis
      was conducted using an inductively coupled plasma mass spectrometry (ICP-MS). Of
      the trace elements investigated, only Hg has a limit set by the European
      Community for human consumption, and this was never exceeded. Nevertheless, based
      on Target Hazard Quotient (THQ) over 1, and on the Estimated Daily Intake per
      meal (EDIm) higher than the Provisional Tolerable Intake (PTI) suggested by the
      Joint FAO/WHO Expert Committee on Food Additive (JECFA), Hg oral exposure derived
      from consumption of the benthonic fish and of the bigger pelagic fish species
      analyzed, could follow the occurrence of systemic effects. Se was found always in
      molar excess respect to Hg in all pelagic fish and in the shellfish, nearly
      equimolar in the benthonic fish. Determining the evidence that foods, such as
      pelagic fish, with high molar excess of Se, could contribute to replace the
      amount of Se bound to Hg and thereby maintaining normal selenoprotein synthesis,
      is useful for a better understanding of the seafood safety. 

PMID- 24433796
TI  - [Debate on the prophylactic application of hepatoprotectants during anti
      tuberculosis treatment].

PMID- 24433797
TI  - [Pay attention to liver injury induced by antituberculosis drugs].

PMID- 24433799
TI  - [Application of liver protection drugs in patients with anti-tuberculosis therapy
      induced liver injury].

PMID- 24433798
TI  - [Pathogenesis and treatment strategies of drug-induced liver injury].

PMID- 24433800
TI  - [Clinical analysis of protionamide and para-aminosalicylic acid induced
      hepatotoxicity in 129 cases].
AB  - OBJECTIVE: To investigate drug-induced liver injury (DILI) in tuberculosis (TB)
      patients treated with protionamide (Pto) and (or) para-aminosalicylic acid (PAS),
      and therefore to provide data for using second-line anti-tuberculosis drugs and
      risk prediction of liver damage. METHODS: A retrospective analysis was performed
      for TB patients treated with regimens containing Pto and (or) PAS in Beijing
      Chest Hospital during Jan. 2008 to Jan. 2013. Cases with DILI were identified,
      and associated factors including patients' age and gender, time of onset,
      severity, clinical manifestations and prognosis of DILI were analyzed. The 2
      groups were compared with chi(2) test. P < 0.05 was considered to be significant.
      RESULTS: A total of 1714 cases were admitted, among whom 226 experienced liver
      damage during treatment, of which 97 cases were excluded because of underlying
      alcoholic liver disease, viral hepatitis B and C. Finally, 129 cases were
      diagnosed as having DILI, resulting in an overall incidence of 7.5% (129/1714),
      being 9.2% (59/641) in females, and 6.5% (70/1073) in males (chi(2) = 4.143, P <
      0.05). DILI in most patients occurred between 1 week to 2 months, with 30.2%
      (39/129) within 2-4 weeks. 47.3% (61/129) of the patients showed no obvious
      clinical symptoms of hepatotoxicity. Among different regimens, combination of
      Pto, PAS and PZA resulted in the highest rate of DILI (20.7%, 19/92), while the
      rate was 9.8% (8/82) for the combination of Pto and PZA, P < 0.05. CONCLUSIONS:
      DILI caused by Pto and PAS should be taken into account, especially in female
      patients and for multi-drug combination therapy. Liver function should be
      monitored even in patients without related clinical manifestations for early
      identification and treatment, and therefore avoiding severe liver damage.

PMID- 24433801
TI  - [Allergic bronchopulmonary aspergillosis in patients with chronic obstructive
      pulmonary disease: report of 3 cases].
AB  - OBJECTIVE: To improve the clinical knowledge on allergic bronchopulmonary
      aspergillosis (ABPA) combined with COPD by report of cases. METHODS: We
      retrospectively analyzed the clinical information of 3 cases of ABPA combined
      with COPD diagnosed in our hospital from Jan. 2009 to Dec. 2012. RESULTS: The 3
      patients were all males, and aged from 68 to 82 years. The main complaints of all
      the patients were exertional dyspnea, cough and sputum production, with episodes
      of wheezing. All patients denied the history of allergic diseases, e.g., asthma,
      rhinitis, sinusitis, eczema, and family history of asthma. They all had a history
      of heavy smoking. The pulmonary function tests indicated obstructive impairment,
      and the ratio of FEV1 to FVC (FEV1/FVC) after bronchodilators were 30%, 33% and
      43%, respectively, with no significant bronchodilator reversibility, which were
      consistent with the diagnostic criteria for COPD, with 1 case in GOLD grade III
      and 2 cases in GOLD grade IV based on the GOLD spirometric criteria for COPD
      severity. Lung HRCT showed emphysema with or without bulla formation. All cases
      showed immediate positive response to Aspergillus antigen by skin prick test
      (SPT), increased serum total IgE > 1000 kU/L, increased serum level of
      Aspergillus specific IgE (>0.35 kU/L) and IgG (>40 mg/L). Central bronchiectasis
      was also evident on HRCT scan in the 3 patients. In addition, the eosinophil
      percentage in peripheral blood was all >5%. Pulmonary infiltrates, brown phlegm
      plugs, and growth of Aspergillus fumigatus were also noted in some cases. After
      the diagnosis of ABPA, the patients were all given oral prednisone therapy, with
      notable improvement in dyspnea and FEV1. CONCLUSIONS: ABPA in COPD is uncommon,
      but early identification and initiation of systemic corticosteroid therapy can
      lead to improvement in symptoms and prognosis. For COPD patients with recurrent
      attacks of wheezing or are unresponsive to combination therapy of inhaled long
      acting bronchodilators and corticosteroids, concurrent ABPA should be suspected
      and investigated accordingly.

PMID- 24433802
TI  - [Optimal cut-off point of symptom association probability in the diagnosis of
      gastroesophageal reflux-induced chronic cough].
AB  - OBJECTIVE: To explore the optimal cut-off point of symptom association
      probability (SAP) in the diagnosis of gastroesophageal reflux-induced chronic
      cough (GERC) and therefore to improve the diagnostic accuracy. METHODS: Patients
      with suspected GERC consecutively referred to our respiratory clinic were
      enrolled into this prospective study between July 2011 and February 2013. After
      multi-channel intraluminal esophageal impedance and pH monitoring, SAP was
      calculated by associating the cough recordings on the patients' diary with the
      detected reflux. GERC was confirmed when there was a favorable response to the
      following anti-reflux therapy despite the laboratory findings. The optimal cutoff
      point of SAP was defined according to the highest Youden index. Then, the
      sensitivity, specificity, positive and negative predictive values, the area under
      the curve of ROC, and the Kappa value for the optimal cut-off point of SAP was
      calculated and compared to those of SAP standards currently used in China or
      generally accepted in the diagnosis of GERC. RESULTS: During the study period,
      103 patients with suspected GERC were recruited. Among them, GERC was confirmed
      in 87 patients (84.5%), including 54 patients (62.1%) due to acid reflux and 33
      patients (37.9%) due to non-acid reflux. The optimal cut-off point of SAP was
      defined at >= 80% based on the highest Youden index of 0.372. For the diagnosis
      of GERC, SAP >= 80% had the area under the curve of ROC of 0.686, the Kappa value
      of 0.264, the sensitivity of 74.7%, the specificity of 62.5%, positive predictive
      value of 91.5% and negative predictive value of 31.3% respectively, which were
      superior to those of SAP >= 75% currently used in China, and to those of SAP >=
      95% ( the generally accepted cut-off) in that the balance between higher
      sensitivity and higher specificity was maintained. When combined with DeMeester
      score >= 12.7, the diagnostic accuracy of SAP >= 80% was further improved, with
      the area under the curve of ROC of 0.820, the Kappa value of 0.689, the
      sensitivity of 87.0%, the specificity of 76.0%, positive predictive value of
      94.1% and negative predictive value of 80.0%. CONCLUSION: SAP >= 80% may be a
      more suitable standard for the diagnosis of GERC.

PMID- 24433803
TI  - [Changes of Th1/Th2 cytokines in immunocompetent patients with pulmonary
      cryptococcosis].
AB  - OBJECTIVE: To study the changes of Th1/Th2 cytokines in immunocompetent patients
      with pulmonary cryptococcosis (PC). METHODS: Twenty immunocompetent patients with
      PC were identified by histopathological examination and enrolled along with the
      age- and gender-matched healthy controls. The serum concentrations of interferon
      gamma (IFN-gamma), interleukin-4 (IL-4) and interleukin-12 (IL-12) were measured
      by enzyme linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells
      (PBMC) in both groups were isolated and incubated with or without recombinant
      human IL-12 (rhIL-12) for 48 hours, and the concentrations of IFN-gamma and IL-4
      in the supernatant were measured by ELISA. RESULTS: (1) Serum IFN-gamma levels
      were significantly decreased in the patients compared with the control group
      [(14.5 +/- 2.7) vs (81.8 +/- 9.8) ng/L (t = 6.590, P < 0.01)], while no
      significant difference was observed in serum IL-12 and IL-4 levels [(2.5 +/- 0.5)
      vs (2.52 +/- 0.6) ng/L and (6.9 +/- 1.3) vs (7.3 +/- 1.5) ng/L, (t = 0.0035 and
      0.2136, P > 0.05) ]. (2) The concentrations of IFN-gamma and IL-4 in the
      supernatant of PBMC without rhIL-12 stimulation showed no differences between the
      2 groups [(55.7 +/- 13.6) vs (51.1 +/- 17.5) ng/L and (5.1 +/- 0.7) vs (5.0 +/-
      0.6) ng/L (t = 0.2979 and 0.0325, P > 0.05) ]. (3) Treatment with rhIL-12
      stimulated the release of IFN-gamma, but the increase in the patients [(4.3 +/-
      0.5) folds] was less compared with that in the controls [(7.9 +/- 1.1) folds] (t
      = 3.01, P < 0.01) , while IL-4 concentration in the supernatant of PBMC was not
      increased in both groups[ (0.9 +/- 0.4) vs (1.3 +/- 0.4) folds (t = 0.7240, P >
      0.05) ]. CONCLUSIONS: Serum Th1 cytokine (IFN-gamma) levels may be dampened in
      immunocompetent patients with PC, without significant change in serum levels of
      Th2 cytokines (IL-4). Deficiency in the response to IL-12 stimulation of Th1
      cells may be one of the underlying mechanisms for the decline in serum IFN-gamma
      levels.

PMID- 24433804
TI  - [The clinical characteristics, treatment and outcome of macrolide-resistant
      Mycoplasma pneumoniae pneumonia in children].
AB  - OBJECTIVE: To investigate the drug resistance of Mycoplasma pneumoniae among
      children with community-acquired pneumonia (CAP), and to explore the clinical and
      radiological characteristics of and the role of azithromycin in the treatment of
      of macrolide-resistant (MR) Mycoplasma pneumoniae pneumonia. METHODS: Cases of
      CAP in children (n = 179) were prospectively enrolled in the Pediatric ward of
      Beijing Chaoyang Hospital from 1st September, 2010 to 31st August 2011.
      Pharyngeal swabs were collected for detection of Mycoplasma pneumoniae DNA.
      Mycoplasma pneumoniae culture and in vitro susceptibility testing were also
      performed. RESULTS: Eighty-three cases met the diagnostic criteria of mycoplasma
      pneumonia, accounting for 46% of the CAP patients. Mycoplasma pneumoniae culture
      was positive in 45 cases, including 44 highly resistant to macrolides (MR) in
      vitro, and 1 sensitive. The 44 cases caused by MR pathogen presented with fever
      for (8 +/- 3) d and cough for (17 +/- 5) d, with higher fever (39.5 +/- 0.7) 
      degrees C and more irritating dry cough. In most of the children, peripheral
      blood leukocytes (8 +/- 4)*10(9)/L were normal, with normal or elevated (0.60 +/-
      0.94) neutrophils, normal or slightly elevated erythrocyte sedimentation rate
      [(24 +/- 14) mm/1 h] and CRP (12.8 mg/L). Chest X-ray showed lobar consolidation
      in 10 cases (23%, 10/44), among them 3 in the lower left lung, 2 in the left
      lung, 3 in the right lower lung, 2 in the right upper lung. Pleural effusion
      (small amount), combined with right lower lung consolidation, was found in 1
      case. Patchy shadows were found in 27 cases, and interstitial lung infiltrate in
      7 cases. Of the 44 cases caused by MR Mycoplasma pneumoniae, 19 had lung computed
      tomography (CT) scanning, among them 13 had lobar or segmental consolidation.
      Azithromycin therapy started in an average of 4.0 days after onset of illness,
      with duration of therapy averaging (9 +/- 4) d. Cephalosporin or penicillin (n =
      1) was the initial antibiotic choice in 12 of them, while combination therapy
      with azithromycin and cephalosporin or penicillin antibiotics was given in 41 of
      them. The duration of fever averaged (6 +/- 3) d after treatment of azithromycin
      and duration of cough averaged (17 +/- 5) d after treatment. Among patients with
      MR Mycoplasma pneumonia, those with lobar consolidation had longer duration of
      fever after treatment with azithromycin, compared with those without
      consolidation (P < 0.05). CONCLUSIONS: The macrolide resistance rate was 98%
      (44/45) in our patients. Fever and duration of therapy with azithromycin in MR
      infection was longer in patients with lobar consolidation. The 44 children with
      MR Mycoplasma pneumonia recovered with no serious complications.

PMID- 24433805
TI  - [A study on the feasibility of CT pulmonary function imaging for screening target
      lung lobes in bronchoscopic lung volume reduction].
AB  - OBJECTIVE: To study the feasibility of CT pulmonary function imaging as a tool
      for screening target lung lobes in bronchoscopic lung volume reduction. METHODS:
      A total of 31 patients with chronic bronchitis were included in the study and all
      of them underwent lung function tests, chest HRCT, and pulmonary ventilation
      perfusion radionuclide scan. According to the lung function results, the patients
      were divided into 2 groups: 9 with normal lung function (normal group) and 22
      with obstructive ventilatory dysfunction (emphysema group). The correlation
      between HRCT visual score, CT imaging parameters of lung function and pulmonary
      function results were analyzed. For each lung lobe, the correlation and
      difference between average CT values, pixel index (PI), and ventilation perfusion
      ratio (V/Q) were also analyzed to explore the reliability of CT lung function
      imaging for determining regional non-functional "target area" in candidate
      patients for bronchoscopic lung volume reduction. RESULTS: There was no
      correlation between HRCT visual scores and lung function test parameters (RV/TLC
      and FEV1/FVC) However, CT lung function imaging evaluation showed a good
      correlation with the lung function test parameters. For individual lung lobes,
      the average CT value and the pixel index (PI = -910 HU) were correlated with the
      corresponding lobe perfusion of the total lung perfusion percentage ratio.
      CONCLUSIONS: CT pulmonary function imaging results were objective, and had a good
      correlation with lung function tests and lung ventilation-perfusion scan results,
      which may be useful as a tool for screening target lung lobes in bronchoscopic
      lung volume reduction.

PMID- 24433806
TI  - [Rational use of hepato-protectants in the prophylaxis and treatment of anti
      tuberculosis drug-induced hepatotoxicity].

PMID- 24433807
TI  - [Anti-tuberculosis therapy in patients with liver diseases and tuberculosis].

PMID- 24433808
TI  - [Immunomodulatory impact of 1, 25-dihydroxyvitamin D3 on tuberculosis].

PMID- 24433809
TI  - [Progress of research in pulmonary alveolar microlithiasis].

PMID- 24433810
TI  - [Advances in researches on risk factors of venous thromboembolism recurrence].

PMID- 24433811
TI  - A review of the current status of laparoscopic and robot-assisted sacrocolpopexy
      for pelvic organ prolapse.
AB  - CONTEXT: Abdominal sacrocolpopexy (ASC) represents the superior treatment for
      apical pelvic organ prolapse (POP) but is associated with increased length of
      stay, analgesic requirement, and cost compared with transvaginal procedures.
      Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) may
      offer shorter postoperative recovery while maintaining equivalent rates of cure.
      OBJECTIVE: This review evaluates the literature on LSC and RSC for clinical
      outcomes and complications. EVIDENCE ACQUISITION: A PubMed search of the
      available literature from 1966 to 2013 on LSC and RSC with a follow-up of at
      least 12 mo was performed. A total of 256 articles were screened, 69 articles
      selected, and outcomes from 26 presented. A review, not meta-analysis, was
      conducted due to the quality of the articles. EVIDENCE SYNTHESIS: LSC has become
      a mature technique with results from 11 patient series encompassing 1221 patients
      with a mean follow-up of 26 mo. Mean operative time was 124 min (range: 55-185)
      with a 3% (range: 0-11%) conversion rate. Objective cure was achieved in 91% of
      patients, with similar satisfaction rates (92%). Six patient series encompassing
      363 patients treated with RSC with a mean follow-up of 28 mo have been reported.
      Mean operative time was 202 min (range: 161-288) with a 1% (range: 0-4%)
      conversion rate. Objective cure rate was 94%, with a 95% subjective success rate.
      Overall, early outcomes and complication rates for both LSC and RSC appeared
      comparable with open ASC. CONCLUSIONS: LSC and RSC provide excellent short- to
      medium-term reconstructive outcomes for patients with POP. RSC is more expensive
      than LSC. Further studies are required to better understand the clinical
      performance of RSC versus LSC and confirm long-term efficacy. PATIENT SUMMARY:
      Laparoscopic and robot-assisted sacrocolpopexy represent attractive minimally
      invasive alternatives to abdominal sacrocolpopexy. They may offer reduced patient
      morbidity but are associated with higher costs.

PMID- 24433812
TI  - Is metastatic prostate cancer changing, and how will we know it? It's time for
      standard nomenclature for nonosseous metastases in clinical trials of patients
      with metastatic castration resistant prostate cancer.
AB  - Successful phenotype-genotype correlation is critically dependent on precise
      definition and reporting of end points in clinical trials. An uniform
      nomenclature for "deep phenotyping" of metastatic sites in patients with
      castration-resistant prostate cancer should be mandated in future clinical drug
      development. 

PMID- 24433814
TI  - Why a governance perspective could contribute to improving drug policy and
      engaging the international development community: lessons from Colombia.

PMID- 24433813
TI  - Piloting a 'spatial isolation' index: the built environment and sexual and drug
      use risks to sex workers.
AB  - BACKGROUND: Employing innovative mapping and spatial analyses of individual and
      neighbourhood environment data, we examined the social, physical and structural
      features of overlapping street-based sex work and drug scenes and explored the
      utility of a 'spatial isolation index' in explaining exchanging sex for drugs and
      exchanging sex while high. METHODS: Analyses drew on baseline interview and
      geographic data (January 2010-October 2011) from a large prospective cohort of
      street and off-street sex workers (SWs) in Metropolitan Vancouver and external
      publically-available, neighbourhood environment data. An index measuring 'spatial
      isolation' was developed from seven indicators measuring features of the built
      environment within 50m buffers (e.g., industrial or commercial zoning, lighting)
      surrounding sex work environments. Bivariate and multivariable logistic
      regression was used to examine associations between the two outcomes (exchanged
      sex for drugs; exchanged sex while high) and the index, as well as each
      individual indicator. RESULTS: Of 510 SWs, 328 worked in street-based/outdoor
      environments (e.g., streets, parks, alleys) and were included in the analyses. In
      multivariable analysis, increased spatial isolation surrounding street
      based/outdoor SWs' main places of servicing clients as measured with the index
      was significantly associated with exchanging sex for drugs. Exchanging sex for
      drugs was also significantly positively associated with an indicator of the built
      environment suggesting greater spatial isolation (increased percent of parks) and
      negatively associated with those suggesting decreased spatial isolation
      (increased percent commercial areas, increased count of lighting, increased
      building footprint). Exchanging sex while high was negatively associated with
      increased percent of commercial zones but this association was removed when
      adjusting for police harassment. CONCLUSIONS: The results from our exploratory
      study highlight how built environment shapes risks within overlapping street
      based sex work and drug scenes through the development of a novel index comprised
      of multiple indicators of the built environment available through publicly
      available data, This study informs the important role that spatially-oriented
      responses, such as safer-environment interventions, and structural responses,
      such as decriminalization of sex work can play in improving the health, safety
      and well-being of SWs.

PMID- 24433815
TI  - Advertising in Actas Dermosifiliograficas, 1909-1939.
AB  - We review advertisements published in the journal Actas Dermosifiliograficas
      between 1909 and 1939. Treatments for sexually transmitted diseases were
      advertised with particular frequency, and they offer a case in point that
      exemplifies the close relationship between the pharmaceutical industry and
      medical journals. 

PMID- 24433816
TI  - Academic performance in relation to adherence to the Mediterranean diet and
      energy balance behaviors in Greek primary schoolchildren.
AB  - OBJECTIVE: To explore possible links between adherence to the Mediterranean Diet
      (MeD), excess body weight, energy balance behaviors, and academic performance in
      Greek primary schoolchildren. DESIGN: Cross-sectional study. SETTING: Primary
      schools in Athens, Greece. PARTICIPANTS: A total of 528 students (256 boys and
      272 girls), 10-12 years of age, were recruited from 21 primary schools in the
      area of Athens, Greece. MAIN OUTCOME MEASURES: Students completed a specifically
      designed energy balance behaviors questionnaire together with the KIDMED index,
      which evaluates the degree of adherence to the MeD. The teacher assessed academic
      performance through a specifically designed, 5-scale questionnaire. Standard
      anthropometric measurements were also taken. ANALYSIS: Block stepwise regression
      analysis was conducted. RESULTS: Adherence to the MeD (beta = .140; P = .001),
      obesity (beta = -.095; P = .001), physical activity levels (beta = .206; P =
      .001), hours of sleep (beta = .100; P = .003), television viewing (beta = -.068;
      P = .05), and global self-esteem levels (beta = .122; P = .001) are significant
      factors in predicting academic performance in primary schoolchildren. CONCLUSIONS
      AND IMPLICATIONS: Poor adherence to the MeD, obesity, and low physical activity
      levels seem to negatively affect academic performance in children. Understanding
      these interrelationships could facilitate the formation of policies focused on
      improving children's academic achievement.

PMID- 24433817
TI  - Manga comic influences snack selection in Black and Hispanic New York City youth.
AB  - OBJECTIVE: To determine whether a single exposure to a Manga comic (Japanese
      comic art) with multiple messages promoting fruit intake influenced snack
      selection in minority urban youth. METHODS: Fifty-seven youth (mean age 10.8 y;
      54% female; 74% black/African American) attending after-school programs in
      Brooklyn, NY participated in a pilot study in which they were randomly assigned
      to receive the comic or a non-health-related newsletter. After reading their
      media, participants were offered a snack and could choose from among
      healthy/unhealthy options. Secondary outcomes included knowledge, self-efficacy,
      and outcome expectations related to fruit intake and media transportation. Data
      were analyzed using regression and paired t test. RESULTS: Comic group
      participants were significantly more likely to choose a healthy snack, compared
      to the Attention-control group (odds ratio = 3.6, 95% confidence interval: 1.1
      12.1, P = .04). The Comic group reported increases in self-efficacy (P = .04) and
      greater transportation (immersion into media) (P = .006). CONCLUSIONS AND
      IMPLICATIONS: Results suggest Manga comics may be a useful format to promote
      healthy snack selection in urban minority youth.

PMID- 24433818
TI  - The frequency of presentation and clinico-pathological characteristics of
      symptomatic versus screen detected ductal carcinoma in situ of the breast.
AB  - INTRODUCTION: DCIS accounts for 20% of screen-detected breast cancers, but also
      presents symptomatically. Historically, approximately 5% of DCIS was thought to
      be symptomatic, but accurate evaluation of the presentation of symptomatic DCIS
      is needed to determine its incidence and tumour biology. METHODS: Clinico
      pathological details of a consecutive series of patients presenting to a single
      breast-unit, with a pre-operative diagnosis of DCIS, were selected. Data included
      age, mode of presentation, pre-operative clinical and radiographical findings.
      The final tumour histology, operation, size, grade, ER status (and HER2
      expression in invasive cases) were recorded. RESULTS: 375 patients had a pre
      operative histological diagnosis of DCIS. 308 (82%) screen-detected (median age
      59), 67 (18%) presented via symptomatic clinics (median age 50). At final
      histology 286 (74%) were pure DCIS, and 67 (23%) had an invasive focus. 43%
      (29/67) of symptomatic cases had an invasive focus at final histology versus 19%
      (60/308) screen-detected (p <= 0.001). 31% (9/29) of symptomatic, versus 10%
      (6/60) of screen-detected cases with invasion were node positive (p = 0.05). 45%
      (28/62) intermediate/high-grade symptomatic cases had an invasive focus at final
      histology, compared to 19% (57/297) intermediate/high-grade screen-detected
      cases. 86% (212/248) screen-detected pure DCIS was ER positive compared to 68%
      (26/38) symptomatically presenting pure DCIS (p <= 0.001). Overall, 13% (38/248)
      pure DCIS presented symptomatically (p = 0.001). CONCLUSIONS: Overall, thirteen
      percent of pure DCIS present symptomatically. Nearly half of symptomatically
      presenting DCIS at core biopsy has an occult invasive focus and is more
      frequently ER negative. Symptomatic DCIS with an invasive focus is more likely to
      have lymph node involvement.

PMID- 24433819
TI  - Aortic valve reconstruction with leaflet replacement and sinotubular junction
      fixation: early and midterm results.
AB  - BACKGROUND: Aortic valve reconstruction surgery (AVRS), consisting of aortic
      leaflet reconstruction with tailored pericardial patches and fixation of the
      sinotubular junction with properly sized fabric rings, is performed for the
      treatment of aortic valve diseases. The early and midterm outcomes of AVRS were
      analyzed. METHODS: Between December 2007 and December 2012, 262 patients with
      isolated aortic valve disease underwent AVRS in one center. Clinical outcomes,
      effective orifice area, mean gradients, and left ventricular mass index were
      evaluated yearly. RESULTS: Mean follow-up duration was 36.0+/-17.1 months and was
      complete in 100% of surviving patients. There was no hospital mortality, but
      there were 3 late deaths (1.1% late mortality). Seven patients (2.7%) required
      reoperation: 5 because of endocarditis and 2 because of suture disruption of the
      leaflets. Ten patients (3.8%) experienced neurologic events. Aortic valve
      regurgitation was absent or trivial in 226 patients (87.3%) and mild in 29
      (11.2%), mild to moderate in 3 (1.2%), and moderate to severe in 1 (0.4%). The
      mean valve gradient and valve orifice index were 10.6+/-5.3 mm Hg and 1.3+/-0.4
      cm2/m2, respectively. CONCLUSIONS: The data from the first 5 years after AVRS
      reveal good clinical and hemodynamic outcomes, suggesting that AVRS is a new
      alternative technique to the practice of replacement with stented bioprostheses
      and mechanical prostheses. However, whether the reconstructed aortic valve
      represents a truly long-term valve remains to be demonstrated.

PMID- 24433820
TI  - An assessment on the recycling opportunities of wastes emanating from scrap metal
      processing in Mauritius.
AB  - This paper presents an assessment on the wastes namely slag, dust, mill scale and
      sludge resulting from scrap metal processing. The aim of this study is to
      demonstrate that there are various ways via which scrap metal processing wastes
      can be reused or recycled in other applications instead of simply diverting them
      to the landfill. These wastes are briefly described and an overview on the
      different areas of applications is presented. Based on the results obtained, the
      waste generation factor developed was 349.3 kg per ton of steel produced and it
      was reported that slag represents 72% of the total wastes emanating from the iron
      and steel industry in Mauritius. Finally the suitability of the different
      treatment and valorisation options in the context of Mauritius is examined.

PMID- 24433821
TI  - Evaluation of new treatment for incipient enamel demineralization using 45S5
      bioglass.
AB  - Bioglass 45S5 is a silica-based bioactive glass capable of depositing a layer of
      hydroxyl carbonate apatite on the surface of the glass when immersed in body
      fluids. The present paper studies a new technique for treating early human dental
      enamel caries lesions by using a paste composed of 45S5 bioglass and phosphoric
      acid. Artificial caries lesions were induced in enamel flat surfaces by means of
      a decalcification solution. All specimens were exposed to a brushing-abrasion
      challenge to test the durability of any newly formed layer resulting from the
      application of 45S5 bioglass paste. The specimens treated with bioglass paste
      showed complete coverage with a layer of brushite crystals. The brushing-abrasion
      challenge did not statistically affect the percentage of enamel coverage with the
      crystalline layer formed by the application of bioglass (p<0.05). These crystals
      were converted to hydroxyapatite crystals when stored in artificial saliva for 14
      days. The current technique suggests the possibility of restoring incipient
      enamel erosive lesion with an abrasion durable layer of hydroxyapatite crystals. 

PMID- 24433822
TI  - The feasibility of using a parenting programme for the prevention of
      unintentional home injuries in the under-fives: a cluster randomised controlled
      trial.
AB  - BACKGROUND: Unintentional injury is the leading cause of preventable death of
      children over the age of 1 year in the UK and a major cause of attendance at
      emergency departments. Children having one injury are at increased risk of
      further injuries. Parenting programmes can reduce injuries in preschool children
      if delivered in the home and on a one-to-one basis. It is not known if group
      based programmes delivered outside the home are effective. OBJECTIVES: To develop
      (1) a parenting programme to prevent recurrent unintentional home injuries in
      preschool children and (2) a tool for parents to report unintentional home
      injuries occurring to their preschool children. To assess the feasibility of
      delivering and evaluating the parenting programme through a cluster randomised
      controlled trial, specifically to (1) assess methods for the recruitment and
      retention of parents; (2) determine the training, equipment and facilities needed
      for the delivery of the programme; (3) establish appropriate primary and
      secondary outcome measures and methods for their collection; (4) determine how
      'normal care' in a comparison arm should be defined; and (5) determine the
      resource utilisation and costing data that would need to be collected for the
      cost-effectiveness component of a future trial; and (6) produce estimates of
      effect sizes to inform sample size estimation for a main trial. DESIGN:
      Feasibility multicentre, cluster, randomised, unblinded trial. SETTING: Eight
      children's centres in Bristol and Nottingham, UK. PARTICIPANTS: Ninety-six
      parents of preschool children who had sustained an unintentional injury requiring
      medical attention in the previous 12 months. INTERVENTIONS: The First-aid Advice
      and Safety Training (FAST) parent programme, comprising parenting support and
      skills combined with first aid and home safety advice. MAIN OUTCOME MEASURES:
      Parent-reported medically attended injuries in the index child and any preschool
      siblings sustained during a 6-month period of observation. RESULTS: An 8-week
      parenting programme was produced, designed with participant-friendly,
      incrementally progressive content. A slimline, month-to-a-view injury calendar,
      spiral bound and suitable for hanging on a wall, was designed for parents to
      record injuries occurring to their preschool children during the 6-month period
      of observed time. Fifty-one parents were recruited (40 meeting eligibility
      criteria plus 11 following 'open invite' to participate); 15 parents completed
      the FAST parent programme and 49 provided data at baseline and during follow-up.
      Completion of the programme was significantly greater for participants using the
      'open invite' approach (85%) than for those recruited using the original
      eligibility criteria (31%). Prototype resource use checklists, unit costs and
      total costs were developed for phases 0, 1 and 2 of the study for use in a future
      trial. CONCLUSIONS: This feasibility study has developed an innovative injury
      prevention intervention and a tool to record parent-reported injuries in
      preschool children. It was not feasible to recruit parents of children who had
      sustained a recent injury, or to ask health visitor teams to identify potential
      participants and to deliver the programme. A trial should target all families
      attending children's centres in disadvantaged areas. The intervention could be
      delivered by a health professional supported by a member of the children's centre
      team in a community setting. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN03605270. SOURCE OF FUNDING: This project was funded by the NIHR Health
      Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 18, No. 3. See the NIHR Journals Library website for
      further project information.

PMID- 24433823
TI  - Diagnosis of twin-to-twin transfusion syndrome, selective fetal growth
      restriction, twin anaemia-polycythaemia sequence, and twin reversed arterial
      perfusion sequence.
AB  - Monochorionic twin pregnancies are well known to be at risk for a variety of
      severe complications, a true challenge for the maternal-fetal medicine
      specialist. With current standards of care, monochorionicity should be
      established in the first trimester. Subsequently, frequent monitoring using the
      appropriate diagnostic tools, and in-depth knowledge about the pathophysiology of
      all possible clinical presentations of monochorionic twin abnormalities, should
      lead to timely recognition, and appropriate management. Virtually all unique
      diseases found in monochorionic twins are directly related to placental angio
      architecture. This, however, cannot be established reliably before birth. The
      clinician needs to be aware of the definitions and symptoms of twin-to twin
      transfusion syndrome, selective fetal growth restriction, twin anaemia
      polycythaemia sequence, and twin reversed arterial perfusion sequence, to be able
      to recognise each disease and take the required action. In this chapter, we
      address current standards on correct and timely diagnoses of severe complications
      of monochorionic twin pregnancies. 

PMID- 24433824
TI  - High-dose, conventionally fractionated thoracic reirradiation for lung tumors.
AB  - BACKGROUND: Loco-regional recurrences and second primary lung tumors are not
      uncommon after high-dose thoracic radiotherapy. The availability of improved
      radiotherapy techniques increases options for reirradiation. We describe a single
      institutional experience with high-dose conventional thoracic reirradiation for
      both loco-regional recurrences and new primary tumors. METHODS: Retrospective
      chart review of patients undergoing reirradiation between February 2004 and
      February 2013. RESULTS: Of 24 patients identified, 54% had a loco-regional
      recurrence, and 46% a new primary tumor. The majority (63%) had stage III NSCLC
      at both initial and second treatment; median interval between treatments was 51
      months (5-189), median follow-up after reirradiation was 19.3 months (95% CI: 2.8
      35.9). Median overall survival (OS) after reirradiation was 13.5 months, with 1
      year survival 51%. Median event-free survival (EFS) was 8.4 months. Median time
      between reirradiation and local progression (n=8) or distant progression (n=8)
      was 6.7 and 11.8 months, respectively. Three patients died with possible grade 5
      bleeding. Other toxicities were uncommon. Planning target volume (PTV) at
      reirradiation was the most important prognostic factor; PTV <300 versus >=300cc
      was significantly associated with median OS (17.4 vs 8.2 months, p=0.03) and EFS
      (14.1 vs 5.5 months, p=0.03). Magnitude of overlap between the initial and
      subsequent PTVs, and between dose distributions, did not influence survival.
      CONCLUSION: Thoracic reirradiation with high dose conventional radiotherapy
      appears to deliver a meaningful survival benefit in low volume new primary or
      recurrent lung cancer. Further studies are needed to confirm these findings, and
      to establish reliable normal tissue tolerance doses for reirradiation.

PMID- 24433825
TI  - Resumption of puberty in girls and boys following removal of the histrelin
      implant.
AB  - OBJECTIVES: To determine time to menarche in girls and testicular volume increase
      in boys after removal of a histrelin implant, which causes profound hypothalamic
      pituitary-gonadal axis suppression. STUDY DESIGN: Medical records of patients
      treated with a histrelin implant were reviewed. Seventy-one patients (56 girls)
      treated with the histrelin implant were identified, of these patients, 37
      explanted girls (68% naive) and 6 explanted boys (83% naive) were included in the
      analysis. Time to menarche after explantation in girls and time to testicular
      volume increase after explantation in boys were determined. Additional variables
      investigated included indication for and duration of treatment, history of
      menarche (girls), previous therapy, and age at beginning and end of histrelin
      treatment. RESULTS: Of the girls, 30 were treated for central precocious puberty
      (CPP), 26 had menarche at an average of 12.75 months after explantation. Of the
      30, 7 were treated for other indications, of whom 6 had reached menarche. In
      girls with CPP, older age at explantation correlated with sooner menarche (P =
      .04). All boys achieved spontaneous testicular enlargement within 1 year of
      explantation. CONCLUSIONS: This study documented resumption of puberty after
      histrelin explantation in treatment naive and non-naive boys and girls with and
      without CPP. Menarche in girls with CPP occurs within a similar timeframe to that
      observed after other treatment approaches.

PMID- 24433826
TI  - Spectrum of disease and outcome in children with symptomatic congenital
      cytomegalovirus infection.
AB  - OBJECTIVE: To evaluate differences in presentation and outcomes in children with
      symptomatic congenital cytomegalovirus (cCMV) identified on newborn screening
      (screened group) and those identified based on clinical findings at birth
      (referred group). STUDY DESIGN: Data on 178 infants with symptomatic cCMV were
      analyzed. Demographic characteristics, clinical and laboratory findings
      documented in the nursery, and sequelae data were compared between the screened
      and the referred groups using chi(2) or Fisher exact test. RESULTS: Two or more
      clinical findings were detected at birth in 91% of referred infants, and only 58%
      of screened infants (P < .001). Significantly more children in the referred group
      had hearing loss compared with screened infants (P = .009). Fifty-one percent of
      screened children were free of sequelae compared with only 28% of the referred
      group (P < .003). CONCLUSIONS: Infants with symptomatic cCMV identified based on
      clinical suspicion have more severe disease at birth and more commonly have
      sequelae than those identified on newborn screening. Inclusion of referral
      infants in many previous reports may have overestimated the severity of disease
      because of selection bias. Defining the complete spectrum of symptomatic disease
      due to cCMV and providing precise estimates of disease burden can only be
      gathered from large newborn screening studies.

PMID- 24433827
TI  - Multifocal vascular tumors and fetal hydrops.

PMID- 24433828
TI  - Oxygen saturation targeting in preterm infants receiving continuous positive
      airway pressure.
AB  - OBJECTIVE: The precision of oxygen saturation (SpO2) targeting in preterm infants
      on continuous positive airway pressure (CPAP) is incompletely characterized. We
      therefore evaluated SpO2 targeting in infants solely receiving CPAP, aiming to
      describe their SpO2 profile, to document the frequency of prolonged hyperoxia and
      hypoxia episodes and of fraction of inspired oxygen (FiO2) adjustments, and to
      explore the relationships with neonatal intensive care unit operational factors.
      STUDY DESIGN: Preterm infants <37 weeks' gestation in 2 neonatal intensive care
      units were studied if they were receiving CPAP and in supplemental oxygen at the
      beginning of each 24-hour recording. SpO2, heart rate, and FiO2 were recorded
      (sampling interval 1-2 seconds). We measured the proportion of time spent in
      predefined SpO2 ranges, the frequency of prolonged episodes (>=30 seconds) of
      SpO2 deviation, and the effect of operational factors including nurse-patient
      ratio. RESULTS: A total of 4034 usable hours of data were recorded from 45
      infants of gestation 30 (27-32) weeks (median [IQR]). When requiring supplemental
      oxygen, infants were in the target SpO2 range (88%-92%) for only 31% (19%-39%) of
      total recording time, with 48 (6.9-90) episodes per 24 hours of severe hyperoxia
      (SpO2 >=98%), and 9.0 (1.6-21) episodes per 24 hours of hypoxia (SpO2 <80%). An
      increased frequency of prolonged hyperoxia in supplemental oxygen was noted when
      nurses were each caring for more patients. Adjustments to FiO2 were made 25 (16
      41) times per day. CONCLUSION: SpO2 targeting is challenging in preterm infants
      receiving CPAP support, with a high proportion of time spent outside the target
      range and frequent prolonged hypoxic and hyperoxic episodes.

PMID- 24433829
TI  - Urine protein biomarkers for the diagnosis and prognosis of necrotizing
      enterocolitis in infants.
AB  - OBJECTIVES: To test the hypothesis that an exploratory proteomics analysis of
      urine proteins with subsequent development of validated urine biomarker panels
      would produce molecular classifiers for both the diagnosis and prognosis of
      infants with necrotizing enterocolitis (NEC). STUDY DESIGN: Urine samples were
      collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time
      of initial clinical concern for disease. The urine from 59 infants was used for
      candidate biomarker discovery by liquid chromatography/mass spectrometry. The
      remaining 60 samples were subject to enzyme-linked immunosorbent assay for
      quantitative biomarker validation. RESULTS: A panel of 7 biomarkers (alpha-2
      macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3,
      fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding
      protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry
      and subsequently validated by enzyme-linked immunosorbent assay. These proteins
      were consistently found to be either up- or down-regulated depending on the
      presence, absence, or severity of disease. Biomarker panel validation resulted in
      a receiver-operator characteristic area under the curve of 98.2% for NEC vs
      sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC.
      CONCLUSIONS: We identified 7 urine proteins capable of providing highly accurate
      diagnostic and prognostic information for infants with suspected NEC. This work
      represents a novel approach to improving the efficiency with which we diagnose
      early NEC and identify those at risk for developing severe, or surgical, disease.

PMID- 24433830
TI  - Extremely elevated cerebrospinal fluid protein levels in a child with neurologic
      symptoms: beware of haemophagocytic lymphohistiocytosis.
AB  - Neurologic symptoms can be the initial manifestation of haemophagocytic
      lymphohistiocytosis (HLH). In this case study, we present a 3-year old boy with a
      clinical picture of encephalitis, a cerebrospinal fluid (CSF) protein level up to
      1165 mg/dl and diffuse cerebral MRI abnormalities. The diagnosis of HLH was
      established only 6 weeks after initial presentation. The boy recovered after HLH
      therapy with persisting mild cognitive defects. Genetic investigation
      demonstrated X-linked lymphoproliferative disease (XLP) as the underlying cause
      of HLH. The extremely elevated protein level in CSF in this case has not yet been
      reported in patients with HLH.

PMID- 24433831
TI  - Progesterone signaling/miR-200a/zeb2 axis regulates self-renewal of mouse
      embryonic stem cells.
AB  - Progesterone is a steroid hormone and plays an important role during pregnancy.
      But the regulation mechanisms of progesterone-progesterone receptor (P4-PR)
      signaling during pregnancy remain largely unknown. In this study, we used
      medroxyprogesterone 17-acetate (MPA) which is a synthetic variant of progesterone
      and has 20-30 times the activity of progesterone to find that at the same
      physiological concentration as progesterone during early pregnancy MPA had no
      significant influence on ES cells self-renewal. But with the increasing of
      dosage, MPA can inhibit the self-renewal capacity of mouse embryonic stem cells
      (ES cells) and promote differentiation untimely. We further determined that MPA
      can influence the miR-200a/zeb2 pathway by down regulating the level of miR-200a.
      miR-200a significantly higher expressed in ES cells to down-regulate the
      expression of zeb2 to inhibit the self-renewal and promote differentiation of ES
      cells. Then we found that the function of MPA can be rescued by over-expression
      of miR-200a or down-regulation of zeb2. Our findings revealed the progesterone
      signaling/miR-200a/zeb2 axis regulating the progesterone signaling to insure the
      balance of self-renewal and differentiation of ES cells. Our study also provided
      new insight into the dosage of progesterone and it's derivant in the hormone
      replacement therapy for pregnant woman. 

PMID- 24433832
TI  - RASSF10 is epigenetically inactivated and induces apoptosis in lung cancer cell
      lines.
AB  - Ras-association domain family 10 (RASSF10), the latest member of the RASSF family
      with Ras effector function, has been frequently inactivated by aberrant promoter
      hypermethylation in several human cancers. However, its role in lung cancer has
      remained unclear. In this study, we investigated the methylation status of
      RASSF10 by combined bisulfate restriction analysis (COBRA) and examined its
      preliminary function in lung cancer cell lines. RASSF10 was methylated in four
      out of six lung cancer cell lines, including NCI-H157, NCI-460, SPCA-1 and NCI
      H446. Treatment with a DNA methylation inhibitor, 5-aza-2'-deoxycytiding (5-aza
      DC), restored RASSF10 mRNA expression and the restoration of RASSF10 increased
      cell apoptosis in a dose dependent manner, whereas knockdown of RASSF10 improved
      cell proliferation ability and inhibited cell apoptosis rate significantly.
      Immunofluorescence revealed that RASSF10 protein was located in the cell
      membrane. Taken together, our data for the first time demonstrates the frequent
      epigenetic inactivation of RASSF10 in lung cancer cell lines. RASSF10 induces
      cell apoptosis and might function as a tumor suppressor gene in lung cancer. 

PMID- 24433833
TI  - Dosimetric effect of Elekta Beam modulator micromultileaf in three-dimensional
      conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer.
AB  - The purpose of this study is to analyze the dosimetric effect of Elekta Beam
      Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity
      modulated radiation therapy (IMRT) for localized prostate cancer. We compared
      treatment plans developed with 2 different Elekta multileaf collimators (MLC):
      Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard
      MLC (10-mm leaf width at the isocenter). The comparison was performed for 15
      patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60
      treatment plans were processed. The dose-volume histograms were used to provide
      the quantitative comparison between plans. In particular, we analyzed differences
      between rectum and bladder sparing in terms of a set of appropriate Vx
      (percentage of organ at risk [OAR] volume receiving the x dose) and differences
      between target conformity and coverage in terms of coverage factor and
      conformation number. Our analysis demonstrates that in 3DCRT there is an
      advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in
      particular, a significant decrease in rectal V60 and V50 (p = 0.001) and in
      bladder V70 and V65 (p = 0.007 and 0.002, respectively) was found. Moreover, a
      better target dose conformity was obtained (p = 0.002). IMRT plans comparison
      demonstrated no significant differences between the use of the 4 or 10-mm MLCs.
      Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives
      a gain in target conformity and in OARs dose sparing whereas in IMRT plans there
      is no advantage. 

PMID- 24433834
TI  - Helical tomotherapy quality assurance with ArcCHECK.
AB  - To design a quality assurance (QA) procedure for helical tomotherapy that
      measures multiple beam parameters with 1 delivery and uses a rotating gantry to
      simulate treatment conditions. The customized QA procedure was preprogrammed on
      the tomotherapy operator station. The dosimetry measurements were performed using
      an ArcCHECK diode array and an A1SL ion chamber inserted in the central holder.
      The ArcCHECK was positioned 10cm above the isocenter so that the 21-cm diameter
      detector array could measure the 40-cm wide tomotherapy beam. During the
      implementation of the new QA procedure, separate comparative measurements were
      made using ion chambers in both liquid and solid water, the tomotherapy onboard
      detector array, and a MapCHECK diode array for a period of 10 weeks. There was
      good agreement (within 1.3%) for the beam output and cone ratio obtained with the
      new procedure and the routine QA measurements. The measured beam energy was
      comparable (0.3%) to solid water measurement during the 10-week evaluation
      period, excluding 2 of the 10 measurements with unusually high background. The
      symmetry reading was similarly compromised for those 2 weeks, and on the other
      weeks, it deviated from the solid water reading by ~2.5%. The ArcCHECK phantom
      presents a suitable alternative for performing helical tomotherapy QA, provided
      the background is collected properly. The proposed weekly procedure using
      ArcCHECK and water phantom makes the QA process more efficient. 

PMID- 24433835
TI  - Myocardial contraction and hyaluronic acid mechanotransduction in epithelial-to
      mesenchymal transformation of endocardial cells.
AB  - Epithelial-to-mesenchymal transition (EMT) of endocardial cells is a critical
      initial step in the formation of heart valves. The collagen gel in vitro model
      has provided significant information on the role of growth factors regulating EMT
      but has not permitted investigation of mechanical factors. Therefore we sought to
      develop a system to probe the effects of mechanical inputs on endocardial EMT by
      incorporating hyaluronic acid (HA), the primary component of endocardial cushions
      in developing heart valves, into the gel assay. This was achieved using a
      combination collagen and crosslinkable methacrylated HA hydrogel (Coll-MeHA).
      Avian atrioventricular canal explants on Coll-MeHA gels showed increased numbers
      of transformed cells. Analysis of the mechanical properties of Coll-MeHA gels
      shows that stiffness does not directly affect EMT. Hydrogel deformation from the
      beating myocardium of explants directly led to higher levels of regional gel
      deformation and larger average strain magnitudes associated with invaded cells on
      Coll-MeHA gels. Inhibition of this contraction reduced EMT on all gel types,
      although to a lesser extent on Coll-MeHA gels. Using the system we have
      developed, which permits the manipulation of mechanical factors, we have
      demonstrated that active mechanical forces play a role in the regulation of
      endocardial EMT.

PMID- 24433837
TI  - A pilot randomised trial to assess the methods and procedures for evaluating the
      clinical effectiveness and cost-effectiveness of Exercise Assisted Reduction then
      Stop (EARS) among disadvantaged smokers.
AB  - BACKGROUND: There have been few rigorous studies on the effects of behavioural
      support for helping smokers to reduce who do not immediately wish to quit. While
      reduction may not have the health benefits of quitting, it may lead smokers to
      want to quit. Physical activity (PA) helps to reduce cravings and withdrawal
      symptoms, and also reduces weight gain after quitting, but smokers may be less
      inclined to exercise. There is scope to develop and determine the effectiveness
      of interventions to support smoking reduction and increase physical activity, for
      those not ready to quit. OBJECTIVE: To conduct a pilot randomised controlled
      trial (RCT) [Exercise Assisted Reduction then Stop (EARS) smoking study] to (1)
      design and evaluate the feasibility and acceptability of a PA and smoking
      reduction counselling intervention [for disadvantaged smokers who do not wish to
      quit but do want to reduce their smoking (to increase the likelihood of
      quitting)], and (2) to inform the design of a large RCT to determine the clinical
      effectiveness and cost-effectiveness of the intervention. DESIGN: A single
      centre, pragmatic, pilot trial with follow-up up to 16 weeks. A mixed methods
      approach assessed the acceptability and feasibility of the intervention and trial
      methods. Smokers were individually randomised to intervention or control arms.
      SETTING: General practices, NHS buildings, community venues, and the Stop Smoking
      Service (SSS) within Plymouth, UK. PARTICIPANTS: Aged > 18 years, smoking >= 10
      cigarettes per day (for >= 2 years) who wished to cut down. We excluded
      individuals who were contraindicated for moderate PA, posed a safety risk to the
      research team, wished to quit immediately or use Nicotine Replacement Therapy,
      not registered with a general practitioner, or did not converse in English.
      INTERVENTION: We designed a client-centred, counselling-based intervention
      designed to support smoking reduction and increases in PA. Support sessions were
      delivered by trained counsellors either face to face or by telephone. Both
      intervention and control arms were given information at baseline on specialist
      SSS support available should they have wished to quit. MAIN OUTCOME MEASURES: The
      primary outcome was 4-week post-quit expired air carbon monoxide (CO)-confirmed
      abstinence from smoking. Secondary outcomes included validated behavioural,
      cognitive and emotional/affective and health-related quality of life measures and
      treatment costs. RESULTS: The study randomised 99 participants, 49 to the
      intervention arm and 50 to the control arm, with a 62% follow-up rate at 16
      weeks. In the intervention and control arms, 14% versus 4%, respectively
      [relative risk = 3.57; 95% confidence interval (CI) 0.78 to 16.35], had expired
      CO-confirmed abstinence at least 4 and up to 8 weeks after quit day; 22% versus
      6% (relative risk = 3.74; 95% CI 1.11 to 12.60) made a quit attempt; 10% versus
      4% (relative risk = 92.55; 95% CI 0.52 to 12.53) achieved point-prevalent
      abstinence at 16 weeks; and 39% versus 20% (relative risk = 1.94; 95% CI 1.01 to
      3.74) achieved at least a 50% reduction in the number of cigarettes smoked daily.
      The percentage reporting using PA for controlling smoking in the intervention
      versus control arms was 55% versus 22%, respectively at 8 weeks and 37% versus
      16%, respectively, at 16 weeks. The counsellors generally delivered the
      intervention as planned and participants responded with a variety of smoking
      reduction strategies, sometimes supported by changes in PA. The intervention
      costs were approximately L192 per participant. Exploratory cost-effectiveness
      modelling indicates that the intervention may be cost-effective. CONCLUSIONS: The
      study provided valuable information on the resources needed to improve study
      recruitment and retention. Offering support for smoking reduction and PA appears
      to have value in promoting reduction and cessation in disadvantaged smokers not
      currently motivated to quit. A large RCT is needed to assess the clinical
      effectiveness and cost-effectiveness of the intervention in this population.
      TRIAL REGISTRATION: ISRCTN 13837944. FUNDING: This project was funded by the NIHR
      Health Technology Assessment programme and will be published in full in Health
      Technology Assessment, Vol. 18, No. 4. See the NIHR Journals Library website for
      further project information.

PMID- 24433836
TI  - Hippocampal injury-induced cognitive and mood dysfunction, altered neurogenesis,
      and epilepsy: can early neural stem cell grafting intervention provide
      protection?
AB  - Damage to the hippocampus can occur through many causes including head trauma,
      ischemia, stroke, status epilepticus, and Alzheimer's disease. Certain changes
      such as increased levels of neurogenesis and elevated concentrations of multiple
      neurotrophic factors that ensue in the acute phase after injury seem beneficial
      for restraining hippocampal dysfunction. However, many alterations that arise in
      the intermediate to chronic phase after injury such as abnormal migration of
      newly born neurons, aberrant synaptic reorganization, progressive loss of
      inhibitory gamma-amino butyric acid positive interneurons including those
      expressing reelin, greatly declined neurogenesis, and sustained inflammation are
      detrimental. Consequently, the net effect of postinjury plasticity in the
      hippocampus remains inadequate for promoting significant functional recovery.
      Hence, ideal therapeutic interventions ought to be efficient for restraining
      these detrimental changes in order to block the propensity of most hippocampal
      injuries to evolve into learning deficits, memory dysfunction, depression, and
      temporal lobe epilepsy. Neural stem cell (NSC) grafting into the hippocampus
      early after injury appears alluring from this perspective because several recent
      studies have demonstrated the therapeutic value of this intervention, especially
      for preventing/easing memory dysfunction, depression, and temporal lobe epilepsy
      development in the chronic phase after injury. These beneficial effects of NSC
      grafting appeared to be mediated through considerable modulation of aberrant
      hippocampal postinjury plasticity with additions of new inhibitory gamma-amino
      butyric acid positive interneurons and astrocytes secreting a variety of
      neurotrophic factors and anticonvulsant proteins. This review presents
      advancements made in NSC grafting therapy for treating hippocampal injury in
      animal models of excitotoxic injury, traumatic brain injury, Alzheimer's disease,
      and status epilepticus; potential mechanisms of functional recovery mediated by
      NSC grafts placed early after hippocampal injury; and issues that need to be
      resolved prior to considering clinical application of NSC grafting for
      hippocampal injury.

PMID- 24433838
TI  - Modified indexing technique for the immediate interim restoration of a dental
      implant.
AB  - Because of the functional and esthetic requirements of patients, different
      techniques have been proposed to reduce the time between dental implant placement
      and interim restoration fabrication. This article describes a modified indexing
      technique by using a surgical template for open-tray impression and definitive
      cast development during immediate loading procedures. This technique does not use
      a complete impression of the oral cavity and, therefore, is more comfortable,
      less time consuming, and less expensive. It also allows the fabrication of
      interim restorations with the optimal shape for developing an adequate emergence
      profile.

PMID- 24433839
TI  - The use of CAD/CAM technology to fabricate a custom ceramic implant abutment: a
      clinical report.
AB  - Well-placed dental implants are a prerequisite of functional and esthetically
      successful dental implant-supported crowns. The presence of soft tissue is
      essential for excellent esthetics because the dental implant or titanium abutment
      may become visible if the soft-tissue contour is not acceptable. This clinical
      report describes the use of a custom ceramic implant abutment designed with
      computer-aided design and computer-aided manufacturing (CAD/CAM) technology by
      milling a zirconia framework that was cemented extraorally to a prefabricated
      titanium abutment with a reduced diameter. This ceramic abutment has the strength
      and precise fit of a titanium interface and also the esthetic advantages of
      shaded custom-milled zirconia, with no visible metal.

PMID- 24433840
TI  - A critical appraisal of the systematic review process: systematic reviews of
      zirconia single crowns.
AB  - STATEMENT OF PROBLEM: Systematic reviews analyze the data of published research
      in an effort to assemble the scientific evidence to help clinicians apply
      evidence-based information in decision making. The quality of systematic reviews
      varies greatly. PURPOSE: The purpose of this study was to critically appraise the
      current systematic review process by evaluating systematic reviews that pertain
      to zirconia-based single crowns. MATERIALS AND METHODS: The following PICO
      (patients, intervention, comparison, outcome) question was formulated: "In
      adults, how does the long-term prognosis of zirconia-based single crowns compare
      with conventional single crowns on natural teeth?" An electronic search was
      performed in PubMed and the Cochran Library for articles published in English
      between 1950 and October 2012. Additional manual searches were completed. To be
      included in the analysis, the study must have been a systematic review, published
      in an English-speaking peer-reviewed journal, and evaluated zirconia crowns on
      teeth. Two examiners qualitatively evaluated the publications with an Assessment
      of Multiple Systematic Reviews checklist and the Oxford Systematic Review
      Appraisal form. RESULTS: Three systematic reviews were identified that met the
      search criteria. Two studies met 5 of the 11 Assessment of Multiple Systematic
      Reviews criteria, whereas the third met only 1 criterion. The same 2 studies met
      3 of the 5 Oxford Systematic Review Appraisal criteria and the third met only 2
      criteria. CONCLUSION: Because of the variation in methodologies, systematic
      reviews should be interpreted cautiously. The Assessment of Multiple Systematic
      Reviews Checklist and the Oxford Systematic Review Appraisal Sheet are practical
      tools for appraising and determining the quality of systematic reviews.

PMID- 24433841
TI  - [Autonomy of the patient with chronic diseases: from passive patient to active
      patient].
AB  - Due to social, economic and cultural changes, there has been a transformation of
      Health Services around the world. A new figure has emerged from this: the Active
      Patient, more responsible, with more information and willing to change his life
      as a chronic patient. In order to respond to this new situation, several
      countries have established initiatives such as self-reliance programmes for
      chronic patients. The aim of this article is to underline the Expert Patient
      Programme Catalonia((r)) and to explain its operation and the results obtained up
      until now. The purpose of this program is to improve the experience of chronic
      disease by patients, from meetings in which an expert patient provides his
      knowledge and experiences to a group of patients with the same disease, with the
      aim of promoting changes in habits and lifestyles that improve the quality of
      life and the coexistence of the person with his chronic process. 

PMID- 24433842
TI  - Reply to: Enzalutamide after failure of docetaxel and abiraterone in metastatic
      castrate resistant prostate cancer.

PMID- 24433843
TI  - Feasibility of preoperative and postoperative chemoradiotherapy in gastric
      adenocarcinoma. Two phase II studies done in parallel. Federation Francophone de
      Cancerologie Digestive 0308.
AB  - BACKGROUND: For resectable gastric cancer, both postoperative chemoradiotherapy
      and perioperative chemotherapy demonstrate high-level evidence for improved
      survival in Western populations. To evaluate the feasibility of pre- or
      postoperative chemoradiotherapy, we proposed two multicentre phase II studies.
      PATIENTS AND METHODS: Patients with localised, histologically confirmed gastric
      cancer and Eastern Cooperative Oncology Group (ECOG) performance status <2 judged
      suitable for curative resection were eligible. Eligible patients were assigned to
      either preoperative chemoradiotherapy followed by surgical resection or surgical
      resection followed by chemoradiotherapy depending on each centre.
      Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil,
      Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200 mg/m2/d by
      continuous infusion 5 days each week. A dose of 50 Gy in 25 fractions in the
      preoperative study, or 45 Gy in 25 fractions in the postoperative study, was
      delivered. The primary end-point for both studies was the proportion of patients,
      who completed the therapeutic sequence. RESULTS: Between September 2007 and
      January 2010, 63 patients were included in both studies. The postoperative study
      was stopped for futility at the first step. In the preoperative study, 31
      patients (73.8%, confidence interval (CI) 95%: 65.8-90.1%) received complete
      therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ
      STO22 (Quality of Life-Stomach module) score were significantly linked with
      chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio
      (OR) 1.16 [CI 95%: 1.01-1.33] and 0.17 [0.03-0.89], p=0.04. Median overall
      survival time was 26.4 months in the preoperative study. CONCLUSION: Feasibility
      of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8
      90.1) and 42.9% (CI 95%: 21.8-66%) in preoperative and postoperative settings
      respectively.

PMID- 24433844
TI  - Reply to Kershaw and Rosenbaum.

PMID- 24433845
TI  - Anomalous coronary origin: from suspicion to surgical revascularization.
AB  - Congenital anomalies of the coronary arteries are uncommon and can present a
      diagnostic challenge. The authors present the case of a patient with recurrent
      chest pain during exertion admitted for acute coronary syndrome. Coronary
      angiography revealed no coronary lesions but showed that the right coronary
      artery originated from the anterolateral aortic wall, above the sinuses of
      Valsalva, leading to suspicion of compression by the pulmonary artery, confirmed
      by CT angiography. The patient underwent surgical revascularization with a good
      result. The authors highlight the need to consider compression of an anomalous
      coronary artery by the pulmonary artery in the differential diagnosis of
      recurrent chest pain on exertion and acute myocardial infarction without
      significant coronary stenosis. 

PMID- 24433846
TI  - Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells
      is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2
      phosphorylation and prostaglandin E2 production.
AB  - INTRODUCTION: Macrophage migration inhibitory factor (MIF) participates in the
      immune response to Toxoplasma gondii, triggers ERK1/2 and prostaglandin E2 (PGE2)
      activation, but there is limited information on these mechanisms in human
      trophoblast. The present study aimed to verify the role of MIF in the ERK1/2
      phosphorylation and PGE2 production, as well as its effect on the susceptibility
      to T. gondii in BeWo cells. METHODS: BeWo cells were treated with increasing
      concentrations of recombinant MIF (rMIF) and/or T. gondii-soluble tachyzoite
      antigen (STAg) and analyzed for ERK1/2 phosphorylation and PGE2 production by
      Western blotting and ELISA, respectively. Cells were also treated with increasing
      concentrations of rMIF, rPGE2, or ERK1/2 inhibitor and tested for T. gondii
      proliferation. The supernatants of cells treated with rPGE2 were assayed for
      cytokine production by ELISA or CBA. RESULTS: ERK1/2 phosphorylation and PGE2
      production increased when the cells were treated with low MIF concentrations
      while the parasitism control occurred only at high MIF concentrations. STAg was
      unable to change ERK1/2 phosphorylation or PGE2 release. BeWo cells demonstrated
      increased T. gondii proliferation and reduced production of pro-inflammatory
      cytokines when treated with PGE2, while PD98059 diminished the parasite
      proliferation. DISCUSSION: The intracellular mechanisms triggered by MIF are dose
      dependent in BeWo cells, and PGE2 is an important factor for the persistence of
      T. gondii at the maternal fetal interface. CONCLUSION: MIF was unable to control
      T. gondii infection in BeWo cells at low concentrations since ERK1/2 and PGE2
      expression were activated, demonstrating a critical effect of these mediators
      favoring parasite proliferation.

PMID- 24433847
TI  - Imaging studies on dopamine transporter and depression: a review of literature
      and suggestions for future research.
AB  - We review the conflicting results from imaging studies of dopamine transporter
      availability in depressed patients and also discuss the heterogeneity of the
      variables involved. Major depression includes diverse clinical manifestations and
      in recent years there has been an increasing interest in the identification of
      homogeneous phenotypes and different clinical subtypes of depression, e.g.
      anhedonic depression, retarded depression, etc. In addition, the use of different
      radioligands and imaging techniques, diverse rating scales, together with the
      lack of control of clinical variables (clinical course, recent or past use of
      substances of abuse, etc.) make it difficult to clearly identify neuronal regions
      or networks with consistently abnormal structures or functions in major
      depressive disorder. It is probably necessary to build a shared approach between
      clinicians and researchers in order to identify standardized procedures to better
      understand the role of the dopamine transporter in depression. We outline a list
      of major issues and also suggest some standardized procedures in collecting
      clinical and imaging data on major depressed patients. Our aim is to delineate a
      possible "modus operandi" that would be a proposal for neuroreceptor studies on
      major depression. 

PMID- 24433848
TI  - Reduced striatal adenosine A2A receptor levels define a molecular subgroup in
      schizophrenia.
AB  - Schizophrenia (SZ) is a mental disorder of unknown origin. Some scientific
      evidence seems to indicate that SZ is not a single disease entity, since there
      are patient groups with clear symptomatic, course and biomarker differences. SZ
      is characterized by a hyperdopaminergic state related to high dopamine D2
      receptor activity. It has also been proposed that there is a hypoadenosynergic
      state. Adenosine is a nucleoside widely distributed in the organism with
      neuromodulative and neuroprotective activity in the central nervous system. In
      the brain, the most abundant adenosine receptors are A1R and A2AR. In the present
      report, we characterize the presence of both receptors in human postmortem
      putamens of patients suffering SZ with real time TaqMan PCR, western blotting and
      radioligand binding assay. We show that A1R levels remain unchanged with respect
      to age-matched controls, whereas nearly fifty percent of patients have reduced
      A2AR, at the transcriptional and translational levels. Moreover, we describe how
      DNA methylation plays a role in the pathological A2AR levels with the bisulfite
      sequencing technique. In fact, an increase in 5-methylcytosine percentage in the
      5' UTR region of ADORA2A was found in those SZ patients with reduced A2AR levels.
      Interestingly, there was a relationship between the A2A/beta-actin ratio and
      motor disturbances as assessed with some items of the PANSS, AIMS and SAS scales.
      Therefore, there may be a subgroup of SZ patients with reduced striatal A2AR
      levels accompanied by an altered motor phenotype. 

PMID- 24433850
TI  - Emergency department waiting times: Do the raw data tell the whole story?
AB  - OBJECTIVE: To determine whether there are real differences in emergency
      department (ED) performance between Australian states and territories. METHODS:
      Cross-sectional analysis of 2009-10 attendances at an ED contributing to the
      Australian non-admitted patient ED care database. The main outcome measure was
      difference in waiting time across triage categories. RESULTS: There were more
      than 5.8 million ED attendances. Raw ED waiting times varied by a range of
      factors including jurisdiction, triage category, geographic location and hospital
      peer group. All variables were significant in a model designed to test the effect
      of jurisdiction on ED waiting times, including triage category, hospital peer
      group, patient socioeconomic status and patient remoteness. When the interaction
      between triage category and jurisdiction entered the model, it was found to have
      a significant effect on ED waiting times (P<0.001) and triage was also
      significant (P<0.001). Jurisdiction was no longer statistically significant
      (P=0.248 using all triage categories and 0.063 using only Australian Triage Scale
      2 and 3). CONCLUSIONS: Although the Council of Australian Governments has adopted
      raw measures for its key ED performance indicators, raw waiting time statistics
      are misleading. There are no consistent differences in ED waiting times between
      states and territories after other factors are accounted for. WHAT IS KNOWN ABOUT
      THE TOPIC? The length of time patients wait to be treated after presenting at an
      ED is routinely used to measure ED performance. In national health agreements
      with the federal government, each state and territory in Australia is expected to
      meet waiting time performance targets for the five ED triage categories. The raw
      data indicate differences in performance between states and territories. WHAT
      DOES THIS PAPER ADD? Measuring ED performance using raw data gives misleading
      results. There are no consistent differences in ED waiting times between the
      states and territories after other factors are taken into account. WHAT ARE THE
      IMPLICATIONS FOR PRACTITIONERS? Judgements regarding differences in performance
      across states and territories for triage waiting times need to take into account
      the mix of patients and the mix of hospitals.

PMID- 24433849
TI  - Cross-diagnostic comparison of visual processing in bipolar disorder and
      schizophrenia.
AB  - Patients with Schizophrenia (SZ) show deficits across various stages of visual
      information processing. Whether patients with Bipolar Disorder (BD) exhibit these
      deficits is unclear. In this study, we conducted a detailed comparison of
      specific stages of early visual perception in BD and SZ. Forty-three BD patients,
      43 SZ patients, and 51 matched healthy control subjects (HC) were administered
      three visual processing paradigms emphasizing: 1) an early stage of object
      formation (location backward masking), 2) a middle stage of object substitution
      (four-dot backward masking), and 3) a later stage at the perception-attention
      interface (rapid serial visual processing (RSVP) task eliciting the attentional
      blink). SZ performed significantly worse than BD and HC on location and four-dot
      masking. BD did not significantly differ from HC on either masking task. Both
      patient groups performed significantly worse than HC on the RSVP task; unlike SZ,
      BD did not show a significant attentional blink effect compared to HC. Our
      results indicate that BD patients were intact at the early and middle stages of
      visual processing (object formation and substitution) but intermediate between
      the SZ and HC groups at a later processing stage involving perceptual and
      attentional processes (RSVP task). These findings suggest that SZ is
      characterized by a diffuse pathophysiology affecting all stages of visual
      processing whereas in BD disruption is only at the latest stage involving higher
      order attentional functions. 

PMID- 24433851
TI  - Development of Strongylus vulgaris-specific serum antibodies in naturally
      infected foals.
AB  - Strongylus vulgaris is regarded as the most pathogenic helminth parasite
      infecting horses. Migrating larvae cause pronounced endarteritis and thrombosis
      in the cranial mesenteric artery and adjacent branches, and thromboembolism can
      lead to ischemia and infarction of large intestinal segments. A recently
      developed serum ELISA allows detection of S. vulgaris-specific antibodies during
      the six-month-long prepatent period. A population of horses has been maintained
      at the University of Kentucky without anthelmintic intervention since 1979, and
      S. vulgaris has been documented to be highly prevalent. In 2012, 12 foals were
      born in this population, and were studied during a 12-month period (March-March).
      Weekly serum samples were collected to monitor S. vulgaris specific antibodies
      with the ELISA. Nine colts underwent necropsy at different time points between 90
      and 300 days of age. At necropsy, Strongylus spp. and Parascaris equorum were
      identified to species and stage and enumerated. Initial statistical findings
      indicate a significant interaction between foal age and ELISA results (p<0.042).
      All foals had initial evidence of S. vulgaris-directed maternal antibodies
      transferred in the colostrum, but then remained ELISA negative during their first
      three months of life. Foals born in February and March became ELISA positive at
      about 12 weeks of age, while those born in April and May went positive at about
      15 and 21 weeks, respectively. Foal date of birth was significantly associated
      with ELISA results (p<0.0001). This could be explained by birth date-dependent
      differences in parasite exposure. One foal remained ELISA-negative throughout the
      course of 30 weeks during the study. A significant association was found between
      ELISA values and larval S. vulgaris burdens (p<0.0001) as well as a three-way
      interaction between S. vulgaris, S. edentatus, and P. equorum burdens (p<0.001).
      A plateau with a subsequent decline in ELISA values corresponded with S. vulgaris
      larvae leaving the bloodstream and migrating back to the intestine. 

PMID- 24433852
TI  - Anthelmintic resistance in equine parasites--current evidence and knowledge gaps.
AB  - Anthelmintic resistance is becoming increasingly prevalent among equine nematode
      parasites. The first reports documenting resistance were published in the 1960s,
      just a short time after introduction of the first modern anthelmintics
      phenothiazine and thiabendazole. Several factors are known to influence
      development of resistance, but evidence specific to equine parasites is limited.
      Most current knowledge and applications have been extrapolated from research with
      trichostrongylid parasites of sheep. The number of cyathostomin species co
      infecting horses adds to the complexity of investigating drug resistance but,
      given their apparent limited biological diversity, viewing these in a unispecific
      context remains a pragmatic approach. Factors affecting resistance development in
      cyathostomins include parasite seasonality, life span and fecundity, host
      immunity, and the existence of encysted stages. Further, parasite refugia have
      been shown to play a vital role in resistance development in other parasites, and
      likely is also important in equine parasites. Specific genetic factors for drug
      resistance and possible modes of inheritance have been identified for
      trichostrongylid nematodes, but it is widely accepted that several more remain
      undiscovered. Current evidence with equine and ruminant parasites suggests that
      fitness is not significantly compromised in drug resistant strains. Attempts to
      develop in vitro and molecular assays for diagnosing anthelmintic resistance in
      equine nematodes have had only limited success, standardized guidelines are
      sorely needed for performing the fecal egg count reduction test in horse
      populations. Taken together, this review illustrates the complexity of
      understanding anthelmintic resistance in equine nematodes, and emphasizes the
      need for further research. 

PMID- 24433853
TI  - Frequency of intestinal parasites in pet dogs from an urban area (Greater Oporto,
      northern Portugal).
AB  - The present study was conducted to evaluate the prevalence of gastrointestinal
      parasites in dogs with no clinical signs (n=175; group H) and in dogs with
      gastrointestinal disease (n=193; group D) that were admitted to a veterinary
      hospital. In group H, the overall prevalence of intestinal parasites (i.e. the
      presence of at least one species) was 20.6%. Cystoisospora canis was the most
      prevalent protozoon (8.0%) followed by Giardia spp. (7.4%); Toxocara canis (5.1%)
      was the most frequent helminth, followed by Trichuris vulpis (1.1%) and
      Toxascaris leonina (0.6%). Among group H, age <= 6 months was found to be a risk
      factor for infection with C. canis and with at least one agent (odds ratio
      [OR]=3.4). In group D parasites were found in 33.7% of the dogs, with Giardia
      spp. (15.5%) being the most prevalent species, followed by C. canis (13.5%), T.
      canis (7.8%), T. vulpis (2.6%) and T. leonina (0.5%). In group D dogs, age <= 6
      months was a risk factor for infection with Giardia spp. (OR=3.2), with C. canis
      (OR=32.7) and with at least one agent (OR=7.2). This study reveals a remarkable
      number of dogs infected but with no clinical signs.

PMID- 24433854
TI  - Reductions in brain 5-HT1B receptor availability in primarily cocaine-dependent
      humans.
AB  - BACKGROUND: Preclinical evidence implicates the serotonin receptor 5
      hydroxytryptamine 1B (5-HT1B) in the effects of cocaine. This study explores 5
      HT1B in humans by examining receptor availability in vivo in subjects whose
      primary addiction is cocaine dependence (CD) using positron emission tomography.
      METHODS: Study participants included 14 medically healthy subjects with CD (mean
      age = 41 +/- 6 years) who were compared with 14 age-matched healthy control
      subjects (mean age = 41 +/- 8 years) with no past or current history of cocaine
      or other illicit substance abuse. Participants underwent magnetic resonance
      imaging followed by positron emission tomography with the highly selective 5-HT1B
      tracer, [(11)C]P943, for purposes of quantifying regional binding potential.
      Voxel-based morphometry and gray matter masking also were employed to control for
      potential partial volume effects. RESULTS: The [(11)C]P943 positron emission
      tomography imaging data in nine candidate regions (amygdala, anterior cingulate
      cortex, caudate, frontal cortex, hypothalamus, pallidum, putamen, thalamus, and
      ventral striatum) showed significant or nearly significant reductions of regional
      binding potential in subjects with CD in three regions: anterior cingulate (-16%,
      p < .01), hypothalamus (-16%, p = .03), and frontal cortex (-7%, p = .08). Voxel
      based morphometry showed significant gray matter reductions in the frontal cortex
      of subjects with CD. After gray matter masking, statistically significant
      reductions in the [(11)C]P943 regional binding potential were either retained
      (anterior cingulate, -14%, p = .01; hypothalamus, -20%, p < .01) or achieved
      (frontal cortex, -14%, p < .01). Whole-brain voxel-wise parameter estimation
      confirmed these results. Secondary analyses were also significant in some regions
      for years of cocaine and daily tobacco use. CONCLUSIONS: The reductions found in
      this study suggest that 5-HT1B receptors may contribute to the etiology or
      expression of CD and potentially represent a target for medication development.

PMID- 24433855
TI  - Clinical practice, resource utilization, and outcomes of device closure of patent
      foramen ovale in pediatrics.
AB  - BACKGROUND: There are few data on patent foramen ovale closure and its outcome in
      children. In this study, we evaluated the current clinical practice, resource
      utilization, and outcome of device closure of patent foramen ovale in children.
      We hypothesized that patent foramen ovale closure would not result in a
      demonstrated benefit in children. METHODS: We undertook a prospective survey of
      all consecutive patients (<20 years) who underwent patent foramen ovale closure
      in our metropolitan area between 1995 and 2010. Differences in proportions were
      tested using the chi-square test or Fisher's exact test where appropriate.
      Differences in group medians were tested using Wilcoxon signed-rank test.
      RESULTS: A total of 153 patients (104 girls), median age 16 years (range 7-19)
      were studied. Indications for patent foramen ovale closure included: (1) migraine
      headache (104; 68%), (2) nonmigraine headache (24; 16%), (3) visual symptoms
      (110; 72%), (4) transient ischemic attack symptoms (42; 28%), and (5) stroke-like
      symptom (24; 16%). Patent foramen ovale was closed with an Amplatzer septal
      occluder in 115 (75%) and a Helex septal occluder in 47 (30%). The mean length of
      hospital stay was 18 +/- 11 hours; the mean hospital charge was $24,126 +/-
      $5808. The median duration of follow-up was 12 months, and 80 patients responded
      to the study survey. On follow-up, symptoms improved in 143 (93%), of which 29
      (19%) had a residual shunt. None of the patient or treatment parameters predicted
      lack of improvement on follow-up. CONCLUSIONS: Despite the lack of proven
      benefit, children undergo closure of the patent foramen ovale for a variety of
      reasons, with the vast majority (92%) of patients reporting significant
      improvement in their symptoms. However, patent foramen ovale closure is an
      expensive procedure with serious potential complications. Symptomatic improvement
      even in the presence of a residual shunt suggests a strong placebo effect.

PMID- 24433856
TI  - Ketogenic diet efficacy in the treatment of intractable epileptic spasms.
AB  - OBJECTIVE: To determine the efficacy of the ketogenic diet in controlling
      epileptic spasms after failing traditional antiepileptic medication therapy.
      METHODS: This is a prospective, case-based study of all infants with epileptic
      spasms who were referred for treatment with the ketogenic diet at our hospital
      between 2009 and 2012. All subjects continued to have epileptic spasms with
      evidence of hypsarrhythmia or severe epileptic encephalopathy on
      electroencephalography despite appropriate medication treatments. The diet
      efficacy was assessed through clinic visits, phone communications, and
      electroencephalography. Quality of life improvement was charted based on the
      caregiver's perspective. RESULTS: Twenty infants (15 males) were included in the
      study. The mean age at seizure onset was 4.5 months. Age at ketogenic diet
      initiation was 0.3 to 2.9 years (mean 1.20, standard deviation 0.78). Fifteen
      patients had epileptic spasms of unknown etiology; three had perinatal hypoxic
      ischemic encephalopathy, one had lissencephaly, and one had STXBP1 mutation.
      Fifteen infants failed to respond to adrenocorticotropin hormone and/or
      vigabatrin before going on the ketogenic diet. Three months after starting the
      diet, >50% seizure reduction was achieved in 70% of patients (95% CI 48-86).
      These results were maintained at 6- and 12-month intervals. All eight of the
      patients followed for 24 months had >50% seizure reduction (95% CI 63-100). At
      least 90% seizure reduction was reported in 20% of patients at 3 months (95% CI 7
      42), 22% (95% CI 8-46) at 6 months, and 35% (95% CI 17-59) at 12 months. The
      majority of patients (63%) achieved improvement of their spasms within 1 month
      after starting the diet. Sixty percent of patients had electroencephalographic
      improvement. All caregivers reported improvement of the quality of life at the 3
      month visit (95% confidence interval 81-100). This ratio was 94% at 6 months (95%
      CI 72-99) and 82% at 12 months (95% CI 58-95). CONCLUSION: The ketogenic diet is
      a safe and potentially effective method of treatment for patients with epileptic
      spasms, especially those who do not respond to customary medication therapies.

PMID- 24433857
TI  - Intra-abdominal benign multicystic peritoneal mesothelioma.
AB  - Benign multicystic peritoneal mesotheliomas are rare: pre-operative diagnosis
      relies on proper imaging. The differential diagnosis includes pseudomyxoma
      peritonei and other peritoneal cysts. Absence of previous surgical resection
      offers the best chance of success when complete resection is performed in a
      specialized center. We report the case of a 43 year-old man with benign
      multicystic peritoneal mesothelioma treated by cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy. 

PMID- 24433858
TI  - alpha-Helix mimetics: outwards and upwards.
AB  - alpha-Helices are common secondary structural elements forming key parts of the
      large, generally featureless interfacial regions of many therapeutically-relevant
      protein-protein interactions (PPIs). The rational design of helix mimetics is an
      appealing small-molecule strategy for the mediation of aberrant PPIs, however the
      first generation of scaffolds presented a relatively small number of residues on
      a single recognition surface. Increasingly, helices involved in PPIs are found to
      have more complex binding modes, utilizing two or three recognition surfaces, or
      binding with extended points of contact. To address these unmet needs the design
      and synthesis of new generations of multi-sided, extended, and supersecondary
      structures are underway. 

PMID- 24433859
TI  - Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of
      human nicotinamide phosphoribosyltransferase (NAMPT).
AB  - The fragment-based identification of two novel and potent biochemical inhibitors
      of the nicotinamide phosphoribosyltransferase (NAMPT) enzyme is described. These
      compounds (51 and 63) incorporate an amide moiety derived from 3-aminopyridine,
      and are thus structurally distinct from other known anti-NAMPT agents. Each
      exhibits potent inhibition of NAMPT biochemical activity (IC50=19 and 15 nM,
      respectively) as well as robust antiproliferative properties in A2780 cell
      culture experiments (IC50=121 and 99 nM, respectively). However, additional
      biological studies indicate that only inhibitor 51 exerts its A2780 cell culture
      effects via a NAMPT-mediated mechanism. The crystal structures of both 51 and 63
      in complex with NAMPT are also independently described.

PMID- 24433860
TI  - Identification of novel 7-amino-5-methyl-1,6-naphthyridin-2(1H)-one derivatives
      as potent PI3K/mTOR dual inhibitors.
AB  - Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of
      rapamycin (mTOR) signaling pathway is one of the most intensively studied
      approaches to cancer therapy. Rational design led to the identification of novel
      7-amino-5-methyl-1,6-naphthyridin-2(1H)-one derivatives as potent PI3K/mTOR dual
      inhibitors. Design, synthesis and structure activity relationship are reported. 

PMID- 24433861
TI  - Antitrypanosomal structure-activity-relationship study of synthetic cynaropicrin
      derivatives.
AB  - Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic
      skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that
      the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite
      Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping
      sickness). In this Letter, chemical derivatization of cynaropicrin and the
      structure-activity-relationship (SAR) study against T. brucei is described. 

PMID- 24433862
TI  - Discovery of MK-7655, a beta-lactamase inhibitor for combination with
      Primaxin(r).
AB  - beta-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic
      side chains were prepared and evaluated as potential partners for combination
      with imipenem to overcome class A and C beta-lactamase mediated antibiotic
      resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C beta
      lactamases in vitro. It effectively restored imipenem's activity against imipenem
      resistant Pseudomonas and Klebsiella strains at clinically achievable
      concentrations. A combination of MK-7655 and Primaxin(r) is currently in phase II
      clinical trials for the treatment of Gram-negative bacterial infections. 

PMID- 24433863
TI  - Heteroarylureas with spirocyclic diamine cores as inhibitors of fatty acid amide
      hydrolase.
AB  - A series of mechanism based heteroaryl urea fatty acid amide hydrolase (FAAH)
      inhibitors with spirocyclic diamine cores is described. A potent member of this
      class, (37), was found to inhibit FAAH centrally, elevate the brain levels of
      three fatty acid ethanolamides [FAAs: anandamide (AEA), oleoyl ethanolamide (OEA)
      and palmitoyl ethanolamide (PEA)], and was moderately efficacious in a rat model
      of neuropathic pain. 

PMID- 24433864
TI  - The difficulty to define progression patterns in patients with early stage
      myelodysplastic syndromes and deletion 5q--new prognostic markers are needed.

PMID- 24433865
TI  - Elacytarabine in relapsed/refractory acute myeloid leukaemia: an evaluation of
      clinical efficacy, pharmacokinetics, cardiac safety and effects on lipid profile.
AB  - Elacytarabine is the elaidic acid ester derivative of cytarabine, designed to
      enter cells independently of nucleoside transporters. Effects of elacytarabine on
      QT interval, serum lipid profile and clinical activity were investigated in 43
      relapsed/refractory AML patients. Mean maximum increase in corrected QT interval
      of 24( +/- 29)ms occurred 48 h after elacytarabine infusion without associated
      arrhythmias or clinical symptoms. A non-clinically significant, elacytarabine
      exposure-dependent increase in cholesterol was caused by a cholesterol rich
      lipoprotein depleted of apolipoprotein B formed by infused phospholipids
      complexing cholesterol. Elacytarabine is clinically active in relapsed/refractory
      AML: overall response rate (CR + CRi) was 44% (16/36 with 7 non-evaluable
      patients) and adverse events were manageable. Clinical Trials.gov Identifier:
      NCT01258816.

PMID- 24433866
TI  - [Social-health characteristics of subjects who make a living will].
AB  - INTRODUCTION: The Living Will (LW) is well publicised, and still largely unknown
      to the general public and health professionals. OBJECTIVE: To describe the
      characteristics of the subjects that formalize a LW related to socio-demographic
      situation, health status, degree of dependence, healthcare characteristics and
      psychosocial aspects. METHOD: Descriptive observational study conducted in the
      Health Area of Albacete including 123 people who formalized the LW in a Will
      Register in 2011. Study variables included: self-perceived health, functional
      status, morbidity, socio-demographic characteristics, use of health services,
      attitudes towards the LW, and psychosocial aspects. RESULTS: Those that made an
      LW, were mainly women (64.2%), had a mean age of 53.3 years (SD: 14.5), higher
      levels of education (61% with at least secondary education), and a lifestyle
      other than living with a partner, and with children (67.5%). The majority were
      self-sufficient for their daily living activities (98.4% to 94.3% for basic and
      instrumental), and suffered from chronic disease (73.2%). Despite lasting
      relationships with their physicians (9.4 years; SD: 7.9), there was very little
      talk about the end of life (18.3%). More than a half had a family member who had
      previously signed a document (54.5%). More than two-thirds (68.5%) considered
      this document useful in the death of a relative, and also a 56.7% had also served
      as a caregiver of a terminal patient. CONCLUSIONS: Middle-aged people,
      predominantly women, formalized an LW most often. They are usually chronic, but
      self-sufficient for their daily living activities, and are convinced that they
      can influence their health situation.

PMID- 24433867
TI  - Upregulation of hepatic melanocortin 4 receptor during rat liver regeneration.
AB  - BACKGROUND: Melanocortin 4 receptor (MC4R) is predominantly recognized to mediate
      energy metabolism and anti-inflammation through the central nervous system.
      However, the expression of MC4R has recently been identified in rat liver and was
      shown to be upregulated during acute phase response. This study aims to
      investigate potential roles of MC4R in liver regeneration. MATERIALS AND METHODS:
      Rat partial hepatectomy (PH) was performed, and MC4R expression was analyzed at
      different time points after resection. Sham-operated animals (SH) served as
      controls. In vitro primary hepatocytes (HCs) were isolated from normal rat liver
      and stimulated with alpha-melanocyte-stimulating hormone (MC4R agonist). Real
      time polymerase chain reaction, Western blot, and immunofluorescence staining
      were applied to detect gene expression. RESULTS: Up to 8 h after PH, hepatic
      messenger RNA of proinflammatory cytokines interleukin 6 and tumor necrosis
      factor alpha reached peak values. Between 8 and 72 h after PH, rat liver
      regeneration was extremely active as assessed by the regeneration indices labeled
      by Ki-67. Immunofluorescence staining indicated that MC4R was mostly expressed in
      hepatocyte nuclear factor 4(+) cells (HCs) and upregulated during rat liver
      regeneration. Concurrently, the expression of hepatic MC4R protein was
      significantly higher in PH than in SH animals, and phosphorylated extracellular
      signal-regulated kinase 1/2 was remarkably increased in PH compared with SH
      animals (P < 0.05, respectively). In vitro experiments showed that the expression
      of proliferating cell nuclear antigen was significantly higher in HCs treated
      with alpha-melanocyte-stimulating hormone than in control HCs, which was
      correlated to the increase of phosphorylated extracellular signal-regulated
      kinase 1/2 and reduction of phosphorylated signal transducer and activator of
      transcription 3 (P < 0.05, respectively). CONCLUSIONS: MC4R is predominantly
      expressed in HCs and upregulated during rat liver regeneration. In vitro
      stimulation of HC MC4R is associated with a modulation of extracellular signal
      regulated kinase and signal transducer and activator of transcription 3 pathways
      regulating liver regeneration.

PMID- 24433868
TI  - Invasive neural interfaces: the perspective of the surgeon.
AB  - BACKGROUND: By implanting electrodes inside peripheral nerves, amputee's
      intentions are picked up and exploited to control novel dexterous sensorized hand
      prostheses. Under the pretext of presenting surgical technique and clinical
      outcomes of the implant of invasive peripheral neural interfaces in a human
      amputee, this article critically comments, from the point of view of the surgeon,
      strengths and weaknesses of the procedure. MATERIALS AND METHODS: Four
      multielectrodes were implanted in the medial and ulnar nerves of a young
      volunteer, which, following a car-crash, had a left transradial amputation. Both
      nerves were approached with a single incision in the medial aspect of the upper
      arm. Four weeks later, the electrodes were removed. RESULTS: Even if the trauma
      and the postamputation plastic processes altered the anatomy, electrodes were
      proficiently implanted with an overall success of 66%. Looking at the procedure
      from the surgeon's viewpoint unveils few still open issues. Electrodes weaknesses
      were related to the absence of stabilizing structures, the cable transit through
      the skin, the implant angle, and the unproven magnetic resonance imaging
      compatibility. Future investigations are needed to definitely address the better
      anesthesia, number and sites of incisions, the nerves to implant, and the
      convenience of performing epineural microdissection. CONCLUSIONS: Invasive neural
      interfaces developmental process almost completely relies on the efforts of
      bioengineers and neurophysiologists; however, the surgeon is responsible for
      intra and perioperative factors. Therefore, he deserves to play a major role also
      at the stage of specifying the requirements, to satisfy the requisites of a safe,
      stable, and long-lasting implant.

PMID- 24433869
TI  - Systematic review with meta-analysis of studies comparing intraoperative
      neuromonitoring of recurrent laryngeal nerves versus visualization alone during
      thyroidectomy.
AB  - BACKGROUND: The role of intraoperative neuromonitoring (IONM) of the recurrent
      laryngeal nerve (RLN) during thyroid surgery is still debatable. The aim of this
      meta-analysis was to evaluate the potential improvement of IONM versus RLN
      visualization alone (VA) in reducing the incidence of vocal cord palsy. METHODS:
      A literature search for studies comparing IONM versus VA during thyroidectomy was
      performed. Studies were reviewed for primary outcome measures: overall,
      transient, and permanent RLN palsy per nerve and per patients at risk; and for
      secondary outcome measures: operative time; overall, transient and permanent RLN
      palsy per nerve at low and high risk; and the results regarding assistance in RLN
      identification before visualization. RESULTS: Twenty studies comparing
      thyroidectomy with and without IONM were reviewed: three prospective, randomized
      trials, seven prospective trials, and ten retrospective, observational studies.
      Overall, 23,512 patients were included, with thyroidectomy performed using IONM
      compared with thyroidectomy by VA. The total number of nerves at risk was 35,513,
      with 24,038 nerves (67.7%) in the IONM group, compared with 11,475 nerves (32.3%)
      in the VA group. The rates of overall RLN palsy per nerve at risk were 3.47% in
      the IONM group and 3.67% in the VA group. The rates of transient RLN palsy per
      nerve at risk were 2.62% in the IONM group and 2.72% in the VA group. The rates
      of permanent RLN palsy per nerve at risk were 0.79% in the IONM group and 0.92%
      and in the VA group. None of these differences were statistically significant,
      and no other differences were found. CONCLUSIONS: The current review with meta
      analysis showed no statistically significant difference in the incidence of RLN
      palsy when using IONM versus VA during thyroidectomy. However, these results must
      be approached with caution, as they were mainly based on data coming from non
      randomized observational studies. Further studies including high-quality
      multicenter, prospective, randomized trials based on strict criteria of
      standardization and subsequent clustered meta-analysis are required to verify the
      outcomes of interest.

PMID- 24433870
TI  - Human C1 inhibitor attenuates liver ischemia-reperfusion injury and promotes
      liver regeneration.
AB  - Liver ischemia-reperfusion injury (IRI) is a well-known cause of morbidity and
      mortality after liver transplantation (LT). Activation of the complement system
      contributes to the pathogenesis of IRI. Effective treatment strategies aimed at
      reducing hepatic IRI and accelerating liver regeneration could offer major
      benefits in LT. Herein, we investigated the effect of C1-esterase inhibitor
      (human) [C1-INH] on IRI and liver regeneration. Mice were subjected to 60-min
      partial IRI, with or without 70% partial hepatectomy, or CCl4-induced acute liver
      failure. Before liver injury, the animals were pretreated with intravenous C1-INH
      or normal saline. Liver IRI was evaluated using serum levels of alanine
      aminotransferase, serum interleukin-6, and histopathology. Liver samples were
      stained for specific markers of regeneration (5-bromo-2'-deoxyuridine [BrdU]
      staining and proliferating cell nuclear antigen [PCNA]). Histology, serum
      interleukin-6, and alanine aminotransferase release revealed that C1-INH
      treatment attenuated liver injury compared with controls. Improved animal
      survival and increased number of BrdU- and PCNA-positive cells were observed in
      C1-INH-treated animals which underwent IRI + partial hepatectomy or CCl4
      injection compared with control group. These data indicate that complement plays
      a key role in IRI and liver regeneration. C1-INH represents a potential
      therapeutic strategy to reduce IRI and promote regeneration in LT. 

PMID- 24433871
TI  - Explicit role of peroxisome proliferator-activated receptor gamma in gallic acid
      mediated protection against ischemia-reperfusion-induced acute kidney injury in
      rats.
AB  - BACKGROUND: Gallic acid is a polyphenolic compound and is reported to be
      renoprotective because of its antioxidant activity in various preclinical
      studies. Gallic acid has been reported to activate peroxisome proliferator
      activated receptor gamma (PPAR-gamma) in vitro. However, the relevance of the
      interplay between gallic acid and PPAR-gamma in various pathologic conditions is
      yet to be established in vivo. The present study investigated the protective role
      of gallic acid against ischemia-reperfusion-induced acute kidney injury (AKI) and
      the possible involvement of PPAR-gamma in gallic acid-mediated renoprotection.
      MATERIALS AND METHODS: The AKI was induced in rats through bilateral clamping of
      renal arteries for 40 min followed by reperfusion for 24 h. The AKI was assessed
      by the quantification of creatinine clearance, blood urea nitrogen, uric acid,
      potassium level, fractional excretion of sodium, and urinary microproteins. The
      oxidative stress in renal tissues was quantified in terms of myeloperoxidase
      activity, thiobarbituric acid reactive substances, superoxide anion generation,
      and reduced glutathione level. The histopathologic changes in renal tissues were
      assessed by hemotoxylin and eosin staining. The rats were administered gallic
      acid (50, 100, and 200 mg/kg) orally for 7 d before subjecting them to AKI.
      RESULTS: The renal ischemia-reperfusion induced significant changes in plasma,
      urinary, and tissue parameters. The administration of gallic acid at three dose
      levels offered a significant protection against renal ischemia-reperfusion
      induced AKI. The prior treatment with PPAR-gamma antagonist, bisphenol A
      diglycidyl ether, significantly abolished the renoprotective effect of gallic
      acid that confirms the involvement of PPAR-gamma in gallic acid-mediated
      renoprotection. CONCLUSIONS: It is concluded that the activation of PPAR-gamma
      significantly contributes toward gallic acid-mediated protection against ischemia
      reperfusion-induced AKI.

PMID- 24433872
TI  - A prospective evaluation of the clinical, histologic, and therapeutic variables
      associated with incidental perineural invasion in cutaneous squamous cell
      carcinoma.
AB  - BACKGROUND: The prognosis and management of incidental perineural invasion (PNI)
      in patients with cutaneous squamous cell carcinoma (CSCC) has not been well
      defined. OBJECTIVE: We sought to investigate the clinical, histologic, and
      treatment characteristics associated with incidental PNI, histologic PNI
      extending beyond the tumor bulk, in patients with CSCC. METHODS: We conducted a
      multicenter prospective analysis of patients with CSCC undergoing Mohs
      micrographic surgery. RESULTS: The incidence of PNI was 4.6% in 753 CSCC cases.
      PNI was significantly associated with tumors of the head and neck (P = .039),
      larger tumor diameter (P < .001), presence of clinically palpable lymphadenopathy
      (P = .012), and recurrent (P < .001) and painful (P < .001) tumors. Further, PNI
      was significantly associated with poor tumor differentiation (P < .001), greater
      tumor thickness (P < .001), a greater number of Mohs stages (P < .001), and
      larger estimated maximum Mohs margin (P < .001) required to clear the tumor.
      LIMITATIONS: The low numbers of patients demonstrating incidental PNI limits this
      study. CONCLUSIONS: The association of incidental PNI with clinicopathological
      indicators of poor prognosis suggests that incidental PNI may serve as a marker
      to improve the precision in the prognostic assessment of patients with CSCC.

PMID- 24433873
TI  - Clinicopathologic and molecular features in cutaneous extranodal natural killer
      /T-cell lymphoma, nasal type, with aggressive and indolent course.
AB  - BACKGROUND: Extranodal natural killer-/T-cell lymphoma, nasal type (ENKTCL-NT) is
      a highly aggressive lymphoma and prognosis is usually poor. The genetic
      background of primary cutaneous cases is poorly understood. OBJECTIVE: We sought
      to evaluate the clinicopathologic features of cutaneous ENKTCL-NT, and the
      prognostic significance of genomic copy number alterations. METHODS: Eight cases
      of cutaneous ENKTCL-NT (5 primary, 2 secondary, 1 no staging performed),
      including 2 patients with an unusually prolonged course of 5 and 23 years, were
      investigated using array comparative genomic hybridization. RESULTS: All patients
      presented with typical clinicopathologic features. Epstein-Barr virus was found
      in neoplastic cells in all specimens. Copy number alterations were detected in
      all 8 cases with losses on 6q (37.5% of cases) and 7p (37.5% of cases), and gains
      on 7q (37.5% of cases) being the most frequent. Complexity of array comparative
      genomic hybridization profile did not correlate with the course of the disease.
      However, an increase of copy number alterations was detected in sequential biopsy
      specimens of 1 long-term survivor. LIMITATIONS: This was a small case series
      retrospective study. CONCLUSION: Clinicopathologic features of cutaneous ENKTCL
      NT are distinctive. Lower number of copy number alterations cannot be used as
      predictor for prolonged survival in cutaneous ENKTCL-NT.

PMID- 24433874
TI  - Treatment of indolent primary cutaneous B-cell lymphomas with subcutaneous
      interferon-alfa.
AB  - BACKGROUND: Interferon-alfa is used in the treatment of primary cutaneous B-cell
      lymphoma (PCBCL). Therapy with interferon-alfa has thus far been reported solely
      in case reports and small case series, mostly describing intralesional use.
      OBJECTIVE: We sought to evaluate efficacy, response rate, time to response,
      duration of response, and safety of subcutaneously administered interferon-alfa
      for the treatment of cutaneous B-cell lymphoma. METHODS: We conducted a
      retrospective chart analysis of patients given the diagnosis of PCBCL and treated
      with interferon-alfa subcutaneously at a tertiary referral center. RESULTS:
      Fifteen patients with indolent subtypes of PCBCL were identified. The overall
      response rate was 66.7%; all responding patients went into complete remission.
      Response was not significantly associated with the maximum tolerated dose. Within
      the median follow-up time of 40 months, 90% of the responders experienced a
      relapse; median duration of response was 15.5 months. Adverse events were
      predominantly mild and in no case led to cessation of therapy. LIMITATIONS:
      Retrospective nature of the analysis and small number of patients because of
      scarcity of the disease are limitations. CONCLUSION: Treatment of indolent PCBCL
      with subcutaneously injected interferon-alfa demonstrated good response rates and
      tolerability. Response was not dose dependent. Relapses were observed in nearly
      all responding patients raising the question of interferon-alfa maintenance
      therapy in PCBCL.

PMID- 24433875
TI  - The prevalence of metabolic syndrome in patients with hidradenitis suppurativa.
AB  - BACKGROUND: Metabolic syndrome is a multifaceted disorder strongly associated
      with increased risk for development of cardiovascular disease. Chronic
      inflammatory diseases have been associated with metabolic syndrome. Hidradenitis
      suppurativa is a chronic inflammatory skin disease with significant physical and
      emotional sequelae. OBJECTIVE: We sought to investigate a possible association
      between hidradenitis suppurativa and metabolic syndrome. METHODS: A retrospective
      chart review of all dermatology clinic encounters over an 18-month period
      identified 366 patients with an appropriate diagnosis of hidradenitis
      suppurativa. A control population was created from patients seen in the same
      clinic during the same time period for the diagnoses of either keloids or verruca
      vulgaris using the matching criteria of age +/-5 years, race, and gender. All
      participants were examined for characteristics of the metabolic syndrome as
      defined by the National Cholesterol Education Program Adult Treatment Program III
      guidelines. RESULTS: The prevalence of metabolic syndrome in patients with
      hidradenitis suppurativa was 50.6%, which was significantly higher than the
      control group at 30.2% (P < .001). LIMITATIONS: This was a retrospective review.
      Some participants could not be analyzed for metabolic syndrome presence as a
      result of missing data points. CONCLUSION: Our results indicate that patients
      with hidradenitis suppurativa may be at high risk for metabolic syndrome.

PMID- 24433876
TI  - Treatment of extramammary Paget disease of the vulva with imiquimod: a
      retrospective, multicenter study by the German Colposcopy Network.
AB  - BACKGROUND: Extramammary Paget disease (EMPD) is a very rare genital neoplasia
      associated with a high frequency of local recurrences. Surgical excision is the
      standard treatment, but results in mutilating procedures in patients with
      advanced or recurrent disease. Case reports have shown clinical responses to
      imiquimod in patients with EMPD, but this therapy has not been evaluated
      systematically. OBJECTIVE: The aim of this study was to evaluate imiquimod as
      local treatment of first-time and recurrent EMPD. METHODS: All cases of biopsy
      proven EMPD of the vulva treated within the German Colposcopy Network or other
      institutions specializing in vulvar diseases in Germany were included in this
      retrospective analysis. RESULTS: A total of 21 women with EMPD treated with
      imiquimod were identified: 11 (52.4%) achieved complete response, 6 (28.6%)
      achieved partial response, and there were no cases of progressive disease. The
      dose and duration of imiquimod differed between patients. The mean duration of
      treatment exceeded 16 weeks in women achieving complete response. LIMITATIONS:
      EMPD is rare and this retrospective study is limited by the small number of
      patients identified. CONCLUSION: When associated cancers and invasive growth are
      excluded, imiquimod appears to be a useful treatment option for recurrent EMPD
      and may avoid extensive mutilating surgical treatment.

PMID- 24433877
TI  - Is transition to disability pension in young people associated with changes in
      risk of attempted suicide?
AB  - BACKGROUND: The aim of the present study was to investigate trajectories of
      suicide attempt risks before and after granting of disability pension in young
      people. METHOD: The analytic sample consisted of all persons 16-30 years old and
      living in Sweden who were granted a disability pension in the years 1995-1997;
      2000-2002 as well as 2005-2006 (n = 26,624). Crude risks and adjusted odds ratios
      for suicide attempt were computed for the 9-year window around the year of
      disability pension receipt by repeated-measures logistic regressions. RESULTS:
      The risk of suicide attempt was found to increase continuously up to the year
      preceding the granting of disability pension in young people, after which the
      risk declined. These trajectories were similar for women and men and for
      disability pension due to mental and somatic diagnoses. Still, the multivariate
      odds ratios for suicide attempts for women and for disability pension due to
      mental disorders were 2.5- and 3.8-fold increased compared with the odds ratios
      for men and disability pension due to somatic disorders, respectively.
      Trajectories of suicide attempts differed for young individuals granted a
      disability pension during 2005-2006 compared with those granted during 1995-1997
      and 2000-2002. CONCLUSIONS: We found an increasing risk of suicide attempt up
      until the granting of a disability pension in young individuals, after which the
      risk decreased. It is of clinical importance to monitor suicide attempt risk
      among young people waiting for the granting of a disability pension.

PMID- 24433878
TI  - Current status of HIV treatment in Asia and the Pacific region.
AB  - Asia and the Pacific represent a diverse group of nations facing HIV epidemic
      profiles of differing severity. Compared to other parts of the world, the burden
      of HIV disease is high in this region because of its large populations. At the
      end of 2011, 5million people were living with HIV in Asia and the Pacific. This
      accounted for 15% of people living with HIV worldwide. The prevalence of people
      living with HIV, as well as access to HIV treatment and care, varies widely
      between countries. Differences between high-income economies and the rest of the
      continent are remarkable. Many high-income countries provide antiretroviral
      therapy (ART) to their citizens. Middle- and low-income countries have rapid ART
      scale-up and are dependent on international funding. This may compromise the
      sustainability of ART availability. In addition, lack of access to second- and
      third-line therapy remains a problem in many countries. The global goal of
      achieving universal access to ART by 2015 requires mainly low- and middle-income
      countries to be targeted. Regional policy should be developed in order to
      identify new infections in key populations, to start earlier treatment, to retain
      patients in care and to maintain funding. 

PMID- 24433879
TI  - Impact of indoor surface material on perceived air quality.
AB  - The material combination impact on perceived indoor air quality for various
      surface interior materials is presented in this paper. The chemical analysis and
      sensory assessments identifies health adverse of indoor air pollutants (TVOCs).
      In this study, emissions and odors from different common indoor surface materials
      were investigated in glass test chamber under standardized conditions. Chemical
      measurements (TVOC concentration) and sensory assessments (odor intensity, air
      acceptability) were done after building materials exposure to standardized
      conditions. The results of the chemical and sensory assessment of individual
      materials and their combinations are compared and discussed within the paper. The
      using possibility of individual material surface sorption ability was
      investigated. The knowledge of targeted sorption effects can be used in the
      interior design phase. The results demonstrate the various sorption abilities of
      various indoor materials as well as the various sorption abilities of the same
      indoor material in various combinations. 

PMID- 24433880
TI  - Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan
      nanoparticles on human hepatoma HepG2 cells.
AB  - Tea polyphenols have strong antioxidant and antitumor activities. However, these
      health benefits are limited due to their poor in vivo stability and low
      bioavailability. Chitosan nanoparticles as delivery systems may provide an
      alternative approach for enhancing bioavailability of poorly absorbed drugs. In
      this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using
      two different chitosan biomaterials, and their antitumor effects were evaluated
      in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis,
      cell apoptosis and cell cycle detection. The results indicated that the tea
      polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous
      distribution in prepared suspension. MTT assay suggested that tea polyphenol
      loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and
      the cytotoxicity rates were increased gradually and appeared an obvious dose
      dependent relationship. Transmission electron microscope images showed that the
      HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited
      some typical apoptotic features, such as microvilli disappearance, margination of
      nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In
      addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak
      inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea
      polyphenols not only induced cancer cell apoptosis, but also promoted their
      necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their
      antitumor effects mainly through inducing cell apoptosis. Our results revealed
      that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on
      tumor cells probably depended on their controlled drug release and effective cell
      delivery. The chitosan nanoparticles themselves as the delivery carrier showed
      limited antitumor effects compared with their encapsulated drugs. 

PMID- 24433881
TI  - Bio-modified carbon nanoparticles loaded with methotrexate possible carrier for
      anticancer drug delivery.
AB  - The modification of carbon nanoparticles (CNPs) using biological molecules is
      important in the field of chemical biology, as the CNPs have the potential to
      deliver the drugs directly to the targeted cells and tissues. We have modified
      the CNPs by coating bovine serum albumin (BSA) on their surfaces and loaded with
      methotrexate (Mtx). Infrared spectra have revealed the coating of BSA and Mtx on
      CNP (CBM). Scanning electron microscopy (SEM) and atomic force microscope (AFM)
      pictures have exhibited the spherical nature of the composite and coating of the
      proteins on CNPs. The prepared CBM biocomposite has exhibited a sustained release
      of drug. MTT assay using A549 lung cancer cell lines has revealed 83% cell death
      at 150 MUg/ml concentration of CBM. These results indicate that CNPs based
      biocomposites may be tried as therapeutic agents in treatment of cancer like
      diseases.

PMID- 24433882
TI  - Investigation of the sample preparation and curing treatment effects on
      mechanical properties and bioactivity of silica rich metakaolin geopolymer.
AB  - In many biomedical applications both the biological and mechanical behaviours of
      implants are of relevant interest; in the orthopaedic field, for example,
      favourable bioactivity and biocompatibility capabilities are necessary, but at
      the same time the mechanical characteristics of the implants must be such as to
      allow one to support the body weight. In the present work, the authors have
      examined the application of geopolymers with composition H24AlK7Si31O79 and ratio
      Si/Al=31 to be used in biomedical field, considering two different preparation
      methods: one of the activators (KOH) has been added as pellets in the potassium
      silicate solution, in the other as a water solution with 8M concentration.
      Moreover, a different water content was used and only some of the synthesized
      samples were heat treated. The chemical and microstructural characterizations of
      those materials have been carried out by Fourier transform infrared spectroscopy
      (FT-IR) and scanning electron microscopy (SEM). Subsequently, the effects of the
      adopted preparation on the mechanical and biological properties have been
      studied: compressive strength tests have demonstrated that more fragile specimens
      were obtained when KOH was added as a solution. The bioactivity was successfully
      evaluated with the soaking of the samples in a simulated body fluid (SBF) for 3
      weeks. The formation of a layer of hydroxyapatite on the surface of the materials
      has been shown both by SEM micrographs and EDS analyses.

PMID- 24433883
TI  - Novel systems for tailored neurotrophic factor release based on hydrogel and
      resorbable glass hollow fibers.
AB  - A novel system for the release of neurotrophic factor into a nerve guidance
      channel (NGC) based on resorbable phosphate glass hollow fibers (50P2O5-30CaO
      9Na2O-3SiO2-3MgO-2.5K2O-2.5TiO2 mol%) in combination with a genipin-crosslinked
      agar/gelatin hydrogel (A/G_GP) is proposed. No negative effect on the growth of
      neonatal olfactory bulb ensheathing cell line (NOBEC) as well as on the
      expression of pro- and anti-apoptotic proteins was measured in vitro in the
      presence of fiber dissolution products in the culture medium. For the release
      studies, fluorescein isothiocyanate-dextran (FD-20), taken as growth factor model
      molecule, was solubilized in different media and introduced into the fiber lumen
      exploiting the capillary action. The fibers were filled with i) FD-20/phosphate
      buffered saline (PBS) solution, ii) FD-20/hydrogel solution before gelation and
      iii) hydrogel before gelation, subsequently lyophilized and then filled with the
      FD-20/PBS solution. The different strategies used for the loading of the FD-20
      into the fibers resulted in different release kinetics. A slower release was
      observed with the use of A/G_GP hydrogel. At last, poly(epsilon-caprolactone)
      (PCL) nerve guides containing the hollow fibers and the hydrogel have been
      fabricated.

PMID- 24433884
TI  - Preparation and characterization of uniform-sized chitosan/silver microspheres
      with antibacterial activities.
AB  - The chitosan/silver microspheres (CAgMs), which possess effective inhibitory on
      microorganisms, were prepared by an inverse-emulsification cross-linking method
      using CS/Ag sol as dispersed phase, whiteruss as continuous phase, and
      glutaraldehyde as crosslinking agent. The size and shape of CAgMs, greatly
      affecting their antibacterial activities, were controlled by varying the
      concentrations of cross-linking agent, emulsifier and CS/Ag colloid. The
      preparation conditions for obtaining uniform-sized microspheres were optimized.
      The morphology of CAgMs was characterized by scanning electron microscopy (SEM)
      and laser particle size analysis. The spherical CAgMs with smooth surface in the
      mean size of ca. 5 MUm exhibited a narrow particle size distribution. Energy
      Dispersive X-ray spectroscopy (EDX) revealed the elemental composition of the
      microspheres. Transmission electron micrographs (TEM) and Fourier transform
      infrared spectroscopy (FTIR) of the microspheres confirmed the formation of
      silver nanoparticles (AgNPs). The X-ray diffraction (XRD) patterns and UV-Visible
      diffuse reflectance spectroscopy (UV-vis DRS) of the sample showed that AgNPs
      with the diameter no more than 20 nm were face-centered cubic crystallites. X-ray
      photoelectron spectroscopy (XPS) proved that AgO bond existed in the
      microspheres. Thermogravimetric analysis (TGA) showed that the starting
      decomposition temperature of CAgMs (ca. 260 degrees C) was much higher than that
      of CS (ca. 160 degrees C), suggesting that the as-prepared CAgMs possessed better
      thermal stability than original CS did. Antimicrobial assays were performed using
      typical Gram bacteria and fungi. The inhibitory effect indicated that the as
      prepared microspheres exerted a stronger antibacterial activity as the
      concentration of the AgNPs is increasing, and the microspheres in smaller size
      had much better antibacterial activity than those in the larger size. The
      antimicrobial mechanism of CAgMs was discussed.

PMID- 24433885
TI  - Hemocompatibility improvement of poly(ethylene terephthalate) via self
      polymerization of dopamine and covalent graft of zwitterions.
AB  - Poly (ethylene terephthalate) (PET) has been widely adopted as a scaffold
      biomaterial, but further hemocompatibility improvement is still needed for wide
      biomedical applications. Inspired by the composition of adhesive proteins in
      mussels, we propose to use self-polymerized dopamine to form a surface-adherent
      polydopamine layer onto PET sheet, followed by Michael addition with N,N
      dimethylethylenediamine (DMDA) to build tertiary amine, and final
      zwitterions(sulfobetaine and carboxybetaine) construction through ring-opening
      reaction. Physicochemical properties of substrates were demonstrated by water
      contact angle measurement, attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The
      hemocompatibility was evaluated by platelet adhesion, hemolytic, and protein
      adsorption. The results showed that the zwitterions immobilized PET endowed with
      improved resistance to nonspecific protein adsorption and platelet adhesion as
      well as nonhemolytic. The zwitterions with desirable hemocompatibility can be
      readily tailored to catheter for various biomedical applications. 

PMID- 24433886
TI  - Molecular dynamics simulation of interlayer water embedded in phospholipid
      bilayer.
AB  - 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayer with a thin layer of water
      molecules inserted in the hydrophobic region was simulated at 300K to observe the
      pore structure formation during escape of the water molecules from the
      hydrophobic region. The transformation of the water slab into a cylindrical
      droplet in the hydrophobic region, which locally deformed the lipid monolayer,
      was prerequisite to the pore formation. If the thickness of the interlayer water
      was increased beyond a critical value, the local deformation was suppressed as
      such deformation would rupture the lipid bilayer. Hence, it was demonstrated that
      the pore structure formation or local permeability of the lipid membrane is
      closely related to the rigidity of the lipid membrane. 

PMID- 24433887
TI  - Fabricating antigen recognition and anti-bioadhesion polymeric surface via a
      photografting polymerization strategy.
AB  - A polymeric platform for immunodiagnostic bioassay was constructed based on
      biostable polymeric support and two functional monomers, low-fouling
      methacryloyloxyethyl phosphorylcholine (MPC) and acrylic acid (AAc), by a
      photografting polymerization approach. Covalent binding of antibody to pAAc
      chains was achieved by activating carboxyl with NHS/EDC partner. The resultant
      surface showed obvious suppression of nonspecific protein adsorption and platelet
      adhesion relative to the control sample, exhibiting good anti-bioadhesion
      performances. Based on the polymer-supported matrix, a highly sensitive antibody
      antigen specific recognition was confirmed in both native plasma and diluted
      human plasma due to the enhanced antibody loading capacity and lowered
      bioadhesion as compared to the reference. 

PMID- 24433888
TI  - Preliminary research on a novel bioactive silicon doped calcium phosphate coating
      on AZ31 magnesium alloy via electrodeposition.
AB  - A silicon doped calcium phosphate coating was obtained successfully on AZ31 alloy
      substrate via pulse electrodeposition. A novel dual-layer structure was observed
      with a porous lamellar-like and outer block-like apatite layer. In vitro
      immersion tests were adopted in simulated body fluid within 28 days of immersion.
      Slow degradation rate obtained from weight loss was observed for the Si-doped Ca
      P coating, which was also consistent with the results of electrochemical
      experiments showing an enhanced corrosion resistance for the coating. Further
      formation of an apatite-like layer on the surface after immersion proved better
      integrity and biomineralization performance of the coating. Biological
      characterization was carried out for viability, proliferation and differentiation
      of MG63 osteoblast-like cells. The coating showed a good cell growth and an
      enhanced cell proliferation. Moreover, an increased activity of osteogenic marker
      ALP was found. All the results demonstrated that the Si-doped calcium phosphate
      was perspective to be used as a coating for magnesium alloy implants to control
      the degradation rate and enhance the bioactivity, which would facilitate the
      rapidity of bone tissue repair.

PMID- 24433889
TI  - Process engineering of high voltage alginate encapsulation of mesenchymal stem
      cells.
AB  - Encapsulation of stem cells in alginate beads is promising as a sophisticated
      drug delivery system in treatment of a wide range of acute and chronic diseases.
      However, common use of air flow encapsulation of cells in alginate beads fails to
      produce beads with narrow size distribution, intact spherical structure and
      controllable sizes that can be scaled up. Here we show that high voltage
      encapsulation (>= 15 kV) can be used to reproducibly generate spherical alginate
      beads (200-400 MUm) with narrow size distribution (+/- 5-7%) in a controlled
      manner under optimized process parameters. Flow rate of alginate solution ranged
      from 0.5 to 10 ml/h allowed producing alginate beads with a size of 320 and 350
      MUm respectively, suggesting that this approach can be scaled up. Moreover, we
      found that applied voltages (15-25 kV) did not alter the viability and
      proliferation of encapsulated mesenchymal stem cells post-encapsulation and
      cryopreservation as compared to air flow. We are the first who employed a
      comparative analysis of electro-spraying and air flow encapsulation to study the
      effect of high voltage on alginate encapsulated cells. This report provides
      background in application of high voltage to encapsulate living cells for further
      medical purposes. Long-term comparison and work on alginate-cell interaction
      within these structures will be forthcoming.

PMID- 24433890
TI  - Grade-1 titanium soaked in a DMEM solution at 37 degrees C.
AB  - DMEM (Dulbecco's modified Eagle medium) solutions are used in performing in vitro
      cell culture experiments to assess the cell biocompatibility of synthetic
      biomaterials. In this study, Hepes-buffered, phenol red- and sodium pyruvate-free
      DMEM solutions were used, for the first time as immersion media at 37 degrees C,
      to test alkali-treated (5M NaOH, 60 degrees C, 24h) grade-1 titanium substrates.
      Such DMEM solutions were found to deposit X-ray-amorphous calcium phosphate
      (ACP), in one or two weeks, on the soaked grade-1 Ti substrates. A limited number
      of previous studies focusing on the biomimetic coating of alkali-treated Ti6Al4V
      coupons in DMEM have actually used different DMEM solutions, which were not Hepes
      buffered and containing phenol red and sodium pyruvate. The previous studies with
      such DMEM solutions reported the deposition of cryptocrystalline apatitic calcium
      phosphate (Ap-CaP) on Ti6Al4V substrates, but not ACP. An inorganic solution
      (free of amino acids, vitamins, glucose, sodium pyruvate and phenol red),
      simulating the ion concentrations of the DMEM solutions, was also used for the
      first time in depositing ACP on grade-1 Ti substrates upon soaking at 37 degrees
      C for only 24h. The solutions and deposits of this study were analyzed by AAS,
      ICP-AES, FTIR, XRD, XPS, and surface profilometry. 

PMID- 24433891
TI  - Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite
      scaffolds for bone tissue engineering.
AB  - In this study, biomorphic poly(dl-lactic-co-glycolic acid)/nano-hydroxyapatite
      (PLGA/nHA) composite scaffolds were successfully prepared using cane as a
      template. The porous morphology, phase, compression characteristics and in vitro
      biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA
      scaffolds as control were investigated. The results showed that the biomorphic
      scaffolds preserved the original honeycomb-like architecture of cane and
      exhibited a bimodal porous structure. The average channel diameter and micropore
      size of the PLGA/nHA composite scaffolds were 164 +/- 52 MUm and 13 +/- 8 MUm,
      respectively, with a porosity of 89.3 +/- 1.4%. The incorporation of nHA into
      PLGA decreased the degree of crystallinity of PLGA, and significantly improved
      the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility
      evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA
      composite scaffolds could better support cell attachment, proliferation and
      differentiation than the biomorphic PLGA scaffolds. The localization depth of
      MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds
      could reach approximately 400 MUm. The results suggested that the biomorphic
      PLGA/nHA composite scaffolds were promising candidates for bone tissue
      engineering.

PMID- 24433892
TI  - Development of a selective and sensitive voltammetric sensor for propylparaben
      based on a nanosized molecularly imprinted polymer-carbon paste electrode.
AB  - The design and construction of a selective voltammetric sensor for propylparaben
      (PP) in cosmetics by using a molecularly imprinted polymer (MIP) as recognition
      element was introduced. The MIP was synthesized by using PP as template and
      methacrylic acid as functional monomer and then incorporated in the carbon paste
      electrode as PP sensor. The molecularly imprinted polymer-carbon paste electrode
      (MIP-CPE) showed very high recognition ability in comparison to non-imprinted
      polymer-carbon paste electrode (NIP-CPE). It was shown that electrode washing
      after PP extraction, led to enhanced selectivity, without noticeably decreasing
      the sensitivity. Some parameters affecting sensor response were optimized, and a
      calibration curve was then plotted using differential pulse voltammetric (DPV)
      technique. A dynamic linear range of 1 nM to 100 nM was obtained. The detection
      limit of the sensor was calculated to be equal to 0.32 nM. The imprinted
      electrode also displayed good selectivity for PP and selectivity coefficients
      were 2.29 and 1.66 for methylparaben (MP) and ethylparaben (EP) respectively.
      Structural analogs, such as phenol and p-hydroxybenzoic acid had almost no
      response. This sensor was used successfully for propylparaben determination in
      cosmetic sample.

PMID- 24433893
TI  - Biopolymeric antimicrobial films: study of the influence of hydroxypropyl
      methylcellulose, tapioca starch and glycerol contents on physical properties.
AB  - Mixture design methodology was applied to study the effect of different levels of
      tapioca starch (TS), hydroxypropyl methylcelullose (HPMC), and glycerol (Gly) on
      the physical properties of biopolymeric films supporting potassium sorbate (KS;
      0.3% w/w) with the goal of contributing to the development of materials for
      preventing food surface contamination. Mechanical properties, water vapour
      permeability (WVP), solubility in water (S) and colour attributes were evaluated
      on the films. HPMC addition produced an increase of elastic modulus (Ec), stress
      at break (sigmab) and S. It also decreased the yellow index (YI) values and the
      strain at break (epsilonb). The study was deepened using the formulation
      containing 2.67 g/100g of TS, 0.67 g/100g of HPMC, 1.67 g/100g Gly and 0.3g/100g
      KS, observing that it behaved as an effective antimicrobial barrier against
      Zygosaccharomyces bailii external contamination. Microstructural analysis allowed
      us to conclude that HPMC incorporation to a TS network decreased roughness of the
      films and it also increased permeability to oxygen (PO2).

PMID- 24433894
TI  - Evaluation of passive oxide layer formation-biocompatibility relationship in NiTi
      shape memory alloys: geometry and body location dependency.
AB  - A systematic set of ex-situ experiments were carried out on Nickel-Titanium
      (NiTi) shape memory alloy (SMA) in order to identify the dependence of its
      biocompatibility on sample geometry and body location. NiTi samples with three
      different geometries were immersed into three different fluids simulating
      different body parts. The changes observed in alloy surface and chemical content
      of fluids upon immersion experiments designed for four different time periods
      were analyzed in terms of ion release, oxide layer formation, and chemical
      composition of the surface layer. The results indicate that both sample geometry
      and immersion fluid significantly affect the alloy biocompatibility, as evidenced
      by the passive oxide layer formation on the alloy surface and ion release from
      the samples. Upon a 30 day immersion period, all three types of NiTi samples
      exhibited lower ion release than the critical value for clinic applications.
      However; a significant amount of ion release was detected in the case of gastric
      fluid, warranting a thorough investigation prior to utility of NiTi in
      gastrointestinal treatments involving long-time contact with tissue. Furthermore,
      certain geometries appear to be safer than the others for each fluid, providing a
      new set of guidelines to follow while designing implants making use of NiTi SMAs
      to be employed in treatments targeting specific body parts.

PMID- 24433895
TI  - Co-electrospun gelatin-poly(L-lactic acid) scaffolds: modulation of mechanical
      properties and chondrocyte response as a function of composition.
AB  - Bio-synthetic scaffolds of interspersed poly(l-lactic acid) (PLLA) and gelatin
      (GEL) fibers are fabricated by co-electrospinning. Tailored PLLA/GEL compositions
      are obtained and GEL crosslinking with genipin provides for the maintenance of
      good fiber morphology. Scaffold tensile mechanical properties are intermediate
      between those of pure PLLA and GEL and vary as a function of PLLA content.
      Primary human chondrocytes grown on the scaffolds exhibit good proliferation and
      increased values of the differentiation parameters, especially for intermediate
      PLLA/GEL compositions. Mineralization tests enable the deposition of a uniform
      layer of poorly crystalline apatite onto the scaffolds, suggesting potential
      applications involving cartilage as well as cartilage-bone interface tissue
      engineering. 

PMID- 24433896
TI  - Pure zinc sulfide quantum dot as highly selective luminescent probe for
      determination of hazardous cyanide ion.
AB  - A rapid and simple fluorescence method is presented for selective and sensitive
      determination of hazardous cyanide ion in aqueous solution based on
      functionalized zinc sulfide (ZnS) quantum dot (QD) as luminescent prob. The ultra
      small ZnS QDs were synthesized using a chemical co-precipitation method in the
      presence of 2-mercaptoethanol (ME) as an efficient capping agent. The prepared
      pure ZnS QDs was applied as an optical sensor for determination of cyanide ions
      in aqueous solutions. ZnS nanoparticles have exhibited a strong fluorescent
      emission at about 424 nm. The fluorescence intensity of QDs is linearly
      proportional to the cyanide ion concentration in the range 2.44*10(-6) to
      2.59*10(-5)M with a detection limit of 1.70*10(-7)M at pH11. The designed
      fluorescent sensor possesses remarkable selectivity for cyanide ion over other
      anions such as Cl(-), Br(-), F(-), I(-), IO3(-), ClO4(-), BrO3(-), CO3(2-), NO2(
      ), NO3(-), SO4(2-), S2O4(2-), C2O4(2-), SCN(-), N3(-), citrate and tartarate with
      negligible influences on the cyanide detection by fluorescence spectroscopy.

PMID- 24433897
TI  - Preparation, characterization, and antibacterial activity studies of silver
      loaded poly(styrene-co-acrylic acid) nanocomposites.
AB  - A simple method for preparing a new type of stable antibacterial agent was
      presented. Monodisperse poly(styrene-co-acrylic acid) (PSA) nanospheres, serving
      as matrices, were synthesized via soap-free emulsion polymerization. Field
      emission scanning electron microscopy micrographs indicated that PSA nanospheres
      have interesting surface microstructures and well-controlled particle size
      distributions. Silver-loaded poly(styrene-co-acrylic acid) (PSA/Ag-NPs)
      nanocomposites were prepared in situ through interfacial reduction of silver
      nitrate with sodium borohydride, and further characterized by transmission
      electron microscopy and X-ray diffraction. Their effects on antibacterial
      activity including inhibition zone, minimum inhibitory concentration (MIC),
      minimum bactericidal concentration (MBC), and bactericidal kinetics were
      evaluated. In the tests, PSA/Ag-NPs nanocomposites showed excellent antibacterial
      activity against both gram-positive Staphylococcus aureus and gram-negative
      Escherichia coli. These nanocomposites are considered to have potential
      application in antibacterial coatings on biomedical devices to reduce nosocomial
      infection rates. 

PMID- 24433898
TI  - The facile and low temperature synthesis of nanophase hydroxyapatite crystals
      using wet chemistry.
AB  - A simple and facile wet chemistry route was used to synthesize nanophase
      hydroxyapatite (HaP) crystals at low temperature. The synthesis was carried out
      at a pH of 11.0 and at a temperature of 37 degrees C. The resulting samples were
      washed several times and subjected to further analysis. XRD studies revealed that
      the HaP crystals were polycrystalline in nature with a crystallite size of ~15-60
      +/- 5 nm. SEM-EDXA images confirmed the presence of calcium (Ca), phosphorous
      (P), and oxygen (O) peaks. Likewise, FTIR confirmed the presence of
      characteristic phosphate and hydroxyl peaks in samples. Lastly, HRTEM images
      clearly showed distinctive lattice fringes positioned in the 100 and 002 planes.
      TGA analysis shows that HaP crystals can withstand higher calcination
      temperatures and are thermally stable.

PMID- 24433899
TI  - Magnetic core-shell Fe3O4@SiO2/MWCNT nanocomposite modified carbon paste
      electrode for amplified electrochemical sensing of uric acid.
AB  - A new type of nanocomposite based on multi-walled carbon nanotubes decorated with
      magnetic core-shell Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2/MWCNTs) was prepared and
      used to fabricate a modified carbon paste electrode (CPE). The nanocomposite was
      characterized by transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Fourier
      transform infrared spectroscopy (FT-IR) techniques. Electrochemical behavior of
      uric acid (UA) was investigated on Fe3O4@SiO2/MWCNTs-CPE by cyclic voltammetry
      (CV) and square wave voltammetry (SWV) in phosphate buffer solution (pH6.0).
      Under the optimized conditions, the peak currents increased linearly with the
      concentration of UA in the range from 0.60 to 100.0 MUM, with a detection limit
      of 0.13 MUM. The proposed sensor was successfully applied for the determination
      of UA in biological fluids.

PMID- 24433900
TI  - First report for voltammetric determination of methyldopa in the presence of
      folic acid and glycine.
AB  - In this study, a carbon paste electrode modified with TiO2 nanoparticles and
      ferrocene monocarboxylic acid (FM) was used to prepare a novel electrochemical
      sensor. The objective of this novel electrode modification was to seek new
      electrochemical performances for the detection of methyldopa in the presence of
      folic acid and glycine. The peak potentials recorded in a phosphate buffer
      solution (PBS) of pH7.0 were 325, 750 and 880 mV vs. Ag/AgCl/KCl (3.0M) for
      methyldopa, folic acid and glycine, respectively. Under the optimum pH of 7.0,
      the oxidation of methyldopa occurred at a potential about 160 mV less positive
      than that of the unmodified carbon paste electrode (CPE). The response of
      catalytic current with methyldopa concentration showed a linear relation in the
      range from 2.0*10(-7) to 1.0*10(-4)M with a detection limit of 8.0 (+/- 0.2)*10(
      8)M.

PMID- 24433901
TI  - Study on the friction of kappa-carrageenan hydrogels in air and aqueous
      environments.
AB  - Understanding the friction mechanism of polysaccharide hydrogels, which is the
      key component of human cartilage that has very low friction coefficient, is
      critical to develop next generation artificial joint replacement materials. In
      this study, the friction of the polysaccharide kappa-carrageenan hydrogel was
      investigated to elucidate the effect of external load, cross-linking density,
      velocity, and environment on friction. Our experimental results show that (1)
      coefficient of friction (COF) decreases with normal load in air and remains
      constant in water, (2) increasing cross-linking density concurrently increases
      friction and is proportional to Young's modulus, (3) COF increases with testing
      velocity in both air and water, and (4) friction is reduced in aqueous
      environment due to the lubricating effect of water. The underlying frictional
      mechanism is discussed on the basis of water transport from bulk to surface and a
      previously proposed "repulsion-adsorption" model. 

PMID- 24433902
TI  - Photodynamic therapy in the cattle protozoan Tritrichomonas foetus cultivated on
      superhydrophilic carbon nanotube.
AB  - Superhydrophilic vertically aligned carbon nanotubes (VACNT-O2) were used for the
      first time as scaffolds for photodynamic therapy (PDT) to induce inhibition of
      cell division in eukaryotic cells. VACNT-O2 scaffolds were produced on Ti
      substrates using plasma enhanced chemical vapor deposition technique and
      functionalized by oxygen plasma. Scanning electron microscopy (SEM) analysis was
      performed to characterize the surface changes of the protozoan and interaction
      with VACNT-O2. Characterization of lipid and total protein expression was
      performed with protozoa that were or not treated with PDT. Quantification of
      protein was conducted using Qubit fluorometer and separated on a polyacrylamide
      gel. SEM analysis showed the release of lipid vesicles by protozoa after the PDT.
      These vesicles were characterized by the PKH26 fluorescent probe. The results
      demonstrated a greater amount of protein released after PDT than in the control.
      When analyzing the protein material in polyacrylamide gel, a significant protein
      expression of approximately 65 kDa was found. A model identified the programmed
      death of Tritrichomonas foetus after the PDT was also proposed.

PMID- 24433903
TI  - Construction and performance characteristics of polymeric membrane electrode and
      coated graphite electrode for the selective determination of Fe3+ ion.
AB  - Novel Fe(3+) ion-selective polymeric membrane electrodes (PMEs) were prepared
      using three different ionophores N-(4-(dimethylamino)benzylidene)thiazol-2-amine
      [L1], 5-((3-methylthiophene-2yl) methyleneamino)-1,3,4-thiadiazole-2-thiol [L2]
      and N-((3-methylthiophene-2yl)methylene)thiazol-2-amine [L3] and their
      potentiometric characteristics were discussed. Effect of various plasticizers and
      anion excluders was also studied in detail and improved performance was observed.
      The best performance was obtained for the membrane electrode having a composition
      of L2:PVC:o-NPOE:NaTPB as 3:38.5:56:2.5 (w/w; mg). A coated graphite electrode
      (CGE) was also prepared with the same composition and compared. CGE is found to
      perform better as it shows a wider working concentration range of 8.3*10(-8)
      1.0*10(-1)molL(-1), a lower detection limit of 2.3*10(-8)molL(-1), and a near
      Nernstian slope of 19.5 +/- 0.4 mVdecade(-1) of activity with a response time of
      10s. The CGE shows a shelf life of 6 weeks and in view of high selectivity, it
      can be used to quantify Fe(3+) ion in water, soil, vegetable and medicinal
      plants. It can also be used as an indicator electrode in potentiometric titration
      of EDTA with Fe(3+) ion.

PMID- 24433904
TI  - Effect of Sr on the bioactivity and corrosion resistance of nanoporous niobium
      oxide coating for orthopaedic applications.
AB  - In this study, strontium incorporated Nb2O5 was synthesized in two different
      proportions by sol-gel methodology and was deposited on 316L SS by spin coating
      method. The synthesis conditions were optimized to obtain a nanoporous
      morphology. The prepared Sr-incorporated Nb2O5 coatings were uniform, smooth and
      well adherent on to the substrate 316L SS. The coatings were characterized by
      attenuated total reflectance-infrared spectroscopy (ATR-IR), X-ray diffraction
      analysis (XRD), scanning electron microscopy (SEM), energy dispersive X-ray
      analysis (EDX), atomic force microscopy (AFM) and transmission electron
      microscopy (TEM) and the formation of Sr-incorporated Nb2O5 coatings with
      nanoporous morphology was confirmed. Static water contact angle measurements
      showed an enhancement in the wettability of the obtained coatings. In vitro
      bioactivity test of the coated substrates showed that 0.05M Sr-incorporated Nb2O5
      coating had better bioactivity compared to 0.1M Sr-incorporated coating. Solution
      analysis studies confirmed the controlled release of Sr ions from the coating,
      which aid and enhance hydroxyapatite (HAp) growth. Electrochemical studies
      confirmed that the coatings provided excellent corrosion protection to the base
      material as increased charge transfer resistance and decreased double layer
      capacitance was observed for the coated substrates. 

PMID- 24433905
TI  - In vitro response of human osteoblasts to multi-step sol-gel derived bioactive
      glass nanoparticles for bone tissue engineering.
AB  - A multi-step sol-gel process was employed to synthesize bioactive glass (BG)
      nanoparticles. Transmission electron microscopy (TEM) revealed that the BG
      nanoparticles were spherical and ranged from 30 to 60 nm in diameter. In vitro
      reactivity of the BG nanoparticles was tested in phosphate buffer saline (PBS),
      Tris-buffer (TRIS), simulated body fluid (SBF), and Dulbecco's modified Eagle's
      medium (DMEM), in comparison with similar sized hydroxyapatite (HA) and silicon
      substituted HA (SiHA) nanoparticles. Bioactivity of the BG nanoparticles was
      confirmed through Fourier transform infrared spectroscopy (FTIR) analysis. It was
      found that bone-like apatite was formed after immersion in SBF at 7 days.
      Solutions containing BG nanoparticles were slightly more alkaline than HA and
      SiHA, suggesting that a more rapid apatite formation on BG was related to
      solution-mediated dissolution. Primary human osteoblast (HOB) cell model was used
      to evaluate biological responses to BG nanoparticles. Lactate dehydrogenase (LDH)
      cytotoxicity assay showed that HOB cells were not adversely affected by the BG
      nanoparticles throughout the 7day test period. Interestingly, MTS assay results
      showed an enhancement in cell proliferation in the presence of BG when compared
      to HA and SiHA nanoparticles. Particularly, statistically significant (p<0.05)
      alkaline phosphatase (ALP) activity of HOB cells was found on the culture
      containing BG nanoparticles, suggesting that the cell differentiation might be
      promoted by BG. Real-time quantitative PCR analysis (qPCR) further confirmed this
      finding, as a significantly higher level of RUNX2 gene expression was recorded on
      the cells cultured in the presence of BG nanoparticles when compared to those
      with HA and SiHA.

PMID- 24433906
TI  - Silver-doped hydroxyapatite coatings formed on Ti-6Al-4V substrates and their
      characterization.
AB  - Coatings with antibacterial components for medical implants are recommended to
      reduce the risk of bacterial infections. Therefore hydroxyapatite (HA) coatings
      with addition of chitosan (CS) and silver (Ag) are proposed in this work in an
      attempt to resolve this problem. Ti-6Al-4V substrates were modified by a chitosan
      film to study the influence of surface modification on the formation of the HA-Ag
      and HA-CS-Ag coatings. Using a thermal substrate method, HA and HA-CS coatings
      doped with Ag(+) were prepared at low substrate temperatures (90 degrees C).
      Coated surfaces were examined using X-ray diffraction and scanning electron
      microscopy. The amount of silver in the deposited coatings was analyzed by atomic
      absorption spectroscopy. From this study it is concluded that the substrate
      surface modified by a chitosan film promotes the coating formation and increases
      the antibacterial activity of produced coatings against a strain of Escherichia
      coli. The adhesion of E. coli (ATCC 25922) to sheep erythrocytes was decreased by
      14% as compared with the reference samples without Ag. It could be explained by
      the inhibition of bacterial adhesins by Ag(+) ions released. The combined action
      of silver ions and chitosan resulted in a 21% decrease in adhesive index. 

PMID- 24433907
TI  - Promising antimicrobial capability of thin film metallic glasses.
AB  - Thin film metallic glasses (TFMGs) are demonstrated to exhibit excellent surface
      flatness, high corrosion resistance and satisfactory hydrophobic properties.
      Moreover, the antimicrobial and biocompatibility abilities of TFMGs are examined
      and the results are compared with the behavior of pure Ag and 316L stainless
      steel. Three TFMGs, Al48Ag37Ti15, Zr54Ti35Si11, and Zr59Ti22Ag19, are prepared by
      sputtering to assess the antimicrobial performance against Staphylococcus aureus,
      Escherichia coli and Pseudomonas aeruginosa, which are the most common nosocomial
      infection pathogens. Experimental results show that the antimicrobial effect of
      the Al- or Ag-containing AlAgTi and ZrTiAg TFMGs is similar to that of the pure
      Ag coating. The ZrTiSi TFMG with no Ag or Al shows poor antimicrobial capability.
      The physical properties of highly smooth surface and hydrophobic nature alone are
      not sufficient to result in promising antimicrobial ability. The chemical metal
      ion release still plays a major role, which should be born in mind in designing
      biomedical devices. 

PMID- 24433908
TI  - Biomaterials from blends of fluoropolymers and corn starch-implant and structural
      aspects.
AB  - The development of polymeric blends to be used as matrices for bone regeneration
      is a hot topic nowadays. In this article we report on the blends composed by corn
      starch and poly(vinylidene fluoride), PVDF, or poly(vinylidene fluoride
      trifluoroethylene), P(VDF-TrFE), to obtain biocompatible materials. Blends were
      produced by compressing/annealing and chemically/structurally characterized by
      micro-Raman scattering and Fourier transform infrared (FTIR) absorption
      spectroscopies, dynamic mechanical analysis (DMA) and scanning electron
      microscopy (SEM), besides in vivo study to evaluate the tissue response.
      Vibrational spectroscopy reveals no chemical interaction between the polymers and
      starch, absence of material degradation due to compressing/annealing process or
      organism implantation, and maintenance of alpha and ferroelectric crystalline
      phases of PVDF and P(VDF-TrFE), respectively. As a consequence of absence of
      interaction between polymers and starch, it was possible to identify by SEM each
      material, with starch acting as filler. Elastic modulus (E') obtained from DMA
      measurement, independent of the material proportion used in blends, reaches
      values close to those of cancellous bone. Finally, the in vivo study in animals
      shows that the blends, regardless of the composition, were tolerated by
      cancellous bone. 

PMID- 24433909
TI  - pH-responsive controlled-release system based on mesoporous bioglass materials
      capped with mineralized hydroxyapatite.
AB  - A controlled release system with pH-responsive ability has been presented.
      Mesoporous bioglass (MBG) was used as the drug carrier and a spontaneous
      mineralization method was adopted to cap the pores of the carrier with
      hydroxyapatite (HAp) and to restrict the drug release. It is a simple and green
      method to realize the ingenious pH-sensitive controlled release. The model drug,
      metformin hydrochloride (MH), was loaded simultaneously with the mineralization
      process. Due to the degradation of HAp at acid environments, the system shows
      well pH-sensitive drug release ability. The release kinetics can be easily
      adjusted by the mineralization time and the ion concentration of media. The
      system is recommended as a promising candidate as a pH-sensitive vehicle for drug
      controlled release to low pH tissues, such as inflammatory sites and tumors. 

PMID- 24433910
TI  - Adhesive strength of medical polymer on anodic oxide nanostructures fabricated on
      biomedical beta-type titanium alloy.
AB  - Anodic oxide nanostructures (nanopores and nanotubes) were fabricated on a
      biomedical beta-type titanium alloy, Ti-29Nb-13Ta-4.6Zr alloy (TNTZ), by
      anodization in order to improve the adhesive strength of a medical polymer,
      segmented polyurethane (SPU), to TNTZ. TNTZ was anodized in 1.0M H3PO4 solution
      with 0.5 mass% NaF using a direct-current power supply at a voltage of 20V. A
      nanoporous structure is formed on TNTZ in the first stage of anodization, and the
      formation of a nanotube structure occurs subsequently beneath the nanoporous
      structure. The nanostructures formed on TNTZ by anodization for less than 3,600s
      exhibit higher adhesive strengths than those formed at longer anodization times.
      The adhesive strength of the SPU coating on the nanoporous structure formed on
      top of TNTZ by anodization for 1,200s improves by 144% compared to that of the
      SPU coating on as-polished TNTZ with a mirror surface. The adhesive strength of
      the SPU coating on the nanotube structure formed on TNTZ by anodization for
      3,600s increases by 50%. These improvements in the adhesive strength of SPU are
      the result of an anchor effect introduced by the nanostructures formed by
      anodization. Fracture occurs at the interface of the nanoporous structure and the
      SPU coating layer. In contrast, in the case that SPU coating has been performed
      on the nanotube structure, fracture occurs inside the nanotubes.

PMID- 24433911
TI  - A simultaneous process of 3D magnesium phosphate scaffold fabrication and
      bioactive substance loading for hard tissue regeneration.
AB  - A novel room temperature process was developed to produce a 3D porous magnesium
      phosphate (MgP) scaffold with high drug load/release efficiency for use in hard
      tissue regeneration through a combination of a paste extruding deposition (PED)
      system and cement chemistry. MgP scaffolds were prepared using a two-step
      process. The first step was fabrication of the 3D porous scaffold green body to
      control both the morphology and pore structure using a PED system without
      hardening. The second step was cementation, which was carried out by immersing
      the scaffold green body in the binder solution for hardening instead of the
      typical sintering process in ceramic scaffold fabrication. Separation of the
      manufacturing process and cement reaction was important to secure enough time to
      fabricate a 3D scaffold with various sizes and architectures under homogeneous
      extruding conditions. Because the whole process is carried out at room
      temperature, the bioactive molecules, which are easily denatured by heat, may
      apply to scaffolds during the process. Lysozyme was selected as a model bioactive
      substance to demonstrate the efficiency of this process; this was directly mixed
      into MgP powder to introduce homogeneous distribution in the scaffold. The
      extruding paste for the PED system was prepared using the MgP-lysozyme blended
      powder as starting materials. That is, both 3D scaffold fabrication and
      functionalization of the scaffold with bioactive substances could be carried out
      simultaneously. This process significantly enhanced both drug loading efficiency
      and release performance compared to the typical sintering process, where the drug
      is generally loaded by adsorption after heat treatment. The MgP scaffold
      developed in this study satisfied the required conditions for scaffolding in hard
      tissue regeneration in an ideal manner, including 3 dimensionally well
      interconnected pore structures, favorable mechanical properties,
      biodegradability, good cell affinity and in vitro biocompatibility; thus, it has
      excellent potential for application in the field of biomaterials. 

PMID- 24433912
TI  - Structure, phases, and mechanical response of Ti-alloy bioactive glass composite
      coatings.
AB  - Porous titanium alloy-bioactive glass composite coatings were manufactured via
      the flame spray deposition process. The porous coatings, targeted for orthodontic
      and bone-fixation applications, were made from bioactive glass (45S5) powder
      blended with either commercially pure titanium (Cp-Ti) or Ti-6Al-4V alloy powder.
      Two sets of spray conditions, two metallic particle size distributions, and two
      glass particle size distributions were used for this study. Negative control
      coatings consisting of pure Ti-6Al-4V alloy or Cp-Ti were sprayed under both
      conditions. The as-sprayed coatings were characterized through quantitative
      optical cross-sectional metallography, X-ray diffraction (XRD), and ASTM Standard
      C633 tensile adhesion testing. Determination of the porosity and glassy phase
      distribution was achieved by using image analysis in accordance with ASTM
      Standard E2109. Theoretical thermodynamic and heat transfer modeling was
      conducted to explain experimental observations. Thermodynamic modeling was
      performed to estimate the flame temperature and chemical environment for each
      spray condition and a lumped capacitance heat transfer model was developed to
      estimate the temperatures attained by each particle. These models were used to
      establish trends among the choice of alloy, spray condition, and particle size
      distribution. The deposition parameters, alloy composition, and alteration of the
      feedstock powder size distribution had a significant effect on the coating
      microstructure, porosity, phases present, mechanical response, and theoretical
      particle temperatures that were attained. The most promising coatings were the Ti
      6Al-4V-based composite coatings, which had bond strength of 20+/-2MPa (n=5) and
      received reinforcement and strengthening from the inclusion of a glassy phase. It
      was shown that the use of the Ti-6Al-4V-bioactive glass composite coatings may be
      a superior choice due to the possible osteoproductivity from the bioactive glass,
      the potential ability to support tissue ingrowth and vascular tissue, and the
      comparable strength to similar coatings. 

PMID- 24433913
TI  - Synthesis of a novel supermagnetic iron oxide nanocomposite hydrogel based on
      graft copolymerization of poly((2-dimethylamino)ethyl methacrylate) onto salep
      for controlled release of drug.
AB  - In this research, a novel supermagnetic iron oxide nanocomposite hydrogel was
      prepared using simultaneous in situ formation of iron oxide nanoparticles (IONs)
      and three-dimensional cross-linked polymer networks based on graft
      copolymerization of poly((2-dimethylamino)ethyl methacrylate) (PDMA) onto salep
      (PDMA-g-salep). The prepared ION-PDMA-g-salep hydrogel was systematically
      characterized by Fourier transform infrared spectroscopy (FT-IR), scanning
      electron microscopy with energy dispersive X-ray analysis (SEM-EDAX),
      transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray
      diffraction (XRD), and vibrating sample magnetometer (VSM). In addition, the ION
      PDMA-g-salep hydrogel exhibits favorable swelling properties that are sensitive
      to temperature, pH, and external magnetic field (EMF). The drug release behavior
      of the prepared hydrogel under EMF, different temperatures and pHs was also
      studied for the evaluation of the release mechanism and determination of
      diffusion coefficients. Finally, the antibacterial activity and cytotoxicity
      studies of the prepared hydrogel were examined. These results suggested that the
      ION-PDMA-g-salep hydrogel could be a promising candidate for biological dressing
      applications. 

PMID- 24433914
TI  - Using casein and oxidized hyaluronic acid to form biocompatible composite
      hydrogels for controlled drug release.
AB  - To develop biocompatible polymeric hydrogels for the in-situ encapsulation and
      controlled release of hydrophilic drugs, the oxidized hyaluronic acid containing
      aldehyde groups was prepared by the reaction between hyaluronic acid and sodium
      periodate, and then used for the first time to crosslink casein protein in
      aqueous system. By changing its aldehyde group content or amount, we found that
      the gelation kinetics and the properties of resultant composite hydrogel could be
      modulated. Particularly, an increase of its aldehyde group content or amount was
      found to result in a shorten gelation time, an enhanced gel strength, a reduced
      swelling ratio and a prolonged drug release. In addition, the as obtained
      composite hydrogel was also evaluated for its in vitro cytotoxicity on L929 mouse
      fibroblast cells and was confirmed to have a good biocompatibility. 

PMID- 24433915
TI  - Biodegradable borosilicate bioactive glass scaffolds with a trabecular
      microstructure for bone repair.
AB  - Three-dimensional porous scaffolds of a borosilicate bioactive glass (designated
      13-93B1), with the composition 6Na2O-8K2O-8MgO-22CaO-18B2O3-36SiO2-2P2O5 (mol%),
      were prepared using a foam replication technique and evaluated in vitro and in
      vivo. Immersion of the scaffolds for 30 days in a simulated body fluid in vitro
      resulted in partial conversion of the glass to a porous hydroxyapatite composed
      of fine needle-like particles. The capacity of the scaffolds to support bone
      formation in vivo was evaluated in non-critical sized defects created in the
      femoral head of rabbits. Eight weeks post-implantation, the scaffolds were
      partially converted to hydroxyapatite, and they were well integrated with newly
      formed bone. When loaded with platelet-rich plasma (PRP), the scaffolds supported
      bone regeneration in segmental defects in the diaphysis of rabbit radii. The
      results indicate that these 13-93B1 scaffolds, loaded with PRP or without PRP,
      are beneficial for bone repair due to their biocompatibility, conversion to
      hydroxyapatite, and in vivo bone regenerative properties.

PMID- 24433916
TI  - Hyaluronan microgel as a potential carrier for protein sustained delivery by
      tailoring the crosslink network.
AB  - Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs
      1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as
      the crosslinker in an inverse microemulsion system for controlling the sustained
      delivery of bovine serum albumin (BSA). With increasing the crosslinker content,
      the average particle size slightly increased from 1.9 +/- 0.3 MUm to 3.6 +/- 0.5
      MUm by dynamic laser scattering analysis. However, the crosslinker content had no
      significant effect on the morphology of HA microgels by scanning and transmission
      electron microscopes. Fourier transform infrared spectroscopy and elemental
      analysis proved more sulfur participated in the crosslink reaction when raising
      the crosslinker amount. The water swelling test confirmed the increasing
      crosslink density with the crosslinker content by calculating the average
      molecular weight between two crosslink points to be 8.25 +/- 2.51 * 10(5), 1.26
      +/- 0.43 * 10(5), 0.96 +/- 0.09 * 10(5), 0.64 +/- 0.03 * 10(5), and 0.11 +/- 0.01
      * 10(5) respectively. The degradation of HA microgels by hyaluronidase slowed
      down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as
      opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the
      surface morphology of HA microgels but seemed to induce their aggregation. The
      increase of crosslink density decreased the BSA loading capacity but facilitated
      its long-term sustained delivery. When the molar ratio of DVS to repeating unit
      of HA reached 3 or higher, similar delivery profiles were obtained. Among all
      these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in
      this system because it possessed both high BSA loading capacity and long-term
      delivery profile simultaneously.

PMID- 24433917
TI  - Influence of operating parameters on surface properties of RF glow discharge
      oxygen plasma treated TiO2/PET film for biomedical application.
AB  - In this paper, a thin transparent titania (TiO2) film was coated on the surface
      of flexible poly(ethylene terephthalate) (PET) film using the sol-gel method. The
      surface properties of the obtained TiO2/PET film were further improved by RF glow
      discharge oxygen plasma as a function of exposure time and discharge power. The
      changes in hydrophilicity of TiO2/PET films were analyzed by contact angle
      measurements and surface energy. The influence of plasma on the surface of the
      TiO2/PET films was analyzed by atomic force microscopy (AFM) as well as the
      change in chemical state and composition that were investigated by X-ray photo
      electron spectroscopy (XPS). The cytotoxicity of the TiO2/PET films was analyzed
      using human osteoblast cells and the bacterial eradication behaviors of TiO2/PET
      films were also evaluated against Staphylococcus bacteria. It was found that the
      surface roughness and incorporation of oxygen containing polar functional groups
      of the plasma treated TiO2/PET films increased substantially as compared to the
      untreated one. Moreover the increased concentration of Ti(3+) on the surface of
      plasma treated TiO2/PET films was due to the transformation of chemical states
      (Ti(4+)->Ti(3+)). These morphological and chemical changes are responsible for
      enhanced hydrophilicity of the TiO2/PET films. Furthermore, the plasma treated
      TiO2/PET film exhibited no citotoxicity against osteoblast cells and
      antibacterial activity against Staphylococcus bacteria which can find application
      in manufacturing of biomedical devices. 

PMID- 24433918
TI  - Aceclofenac microspheres: quality by design approach.
AB  - The purpose of this study was to prepare polymeric microspheres containing
      aceclofenac by single emulsion [oil-in-water (o/w)] solvent evaporation method.
      Two biocompatible polymers, ethylcellulose, and Eudragit(r) RS100 were used in
      combination. Seven processing factors were investigated by Plackett-Burman design
      (PBD) in order to enhance the encapsulation efficiency of the microspheres. A
      Plackett-Burman design was employed by using the Design-Expert(r) software
      (Version-8.0.7.1). The resultant microspheres were characterized for their size,
      morphology, encapsulation efficiency, and drug release. Imaging of particles was
      performed by field emission scanning electron microscopy. Interaction between the
      drug and polymers were investigated by Fourier transform infrared (FTIR)
      spectroscopy, and X-ray powder diffractometry (XRPD). Graphical and mathematical
      analyses of the design showed that Eudragit(r) RS100, and polyvinyl alcohol (PVA)
      were significant negative effect on the encapsulation efficiency and identified
      as the significant factor determining the encapsulation efficiency of the
      microspheres. The low magnitudes of error and the significant values of R(2) in
      the present investigation prove the high prognostic ability of the design. The
      microspheres showed high encapsulation efficiency (70.15% to 83.82%). The
      microspheres were found to be discrete, oval with smooth surface. The FTIR
      analysis confirmed the compatibility of aceclofenac with the polymers. The XRPD
      revealed the dispersion of drug within microspheres formulation. Perfect
      prolonged drug release profile over 12h was achieved by a combination of
      ethylcellulose, and Eudragit(r) RS100 polymers. In conclusion, polymeric
      microspheres containing aceclofenac can be successfully prepared using the
      technique of experimental design, and these results helped in finding the optimum
      formulation variables for encapsulation efficiency of microspheres. 

PMID- 24433919
TI  - Precipitation of beta' phase and hardening in dental-casting Ag-20Pd-12Au-14.5Cu
      alloys subjected to aging treatments.
AB  - The age-hardening behavior of the dental-casting Ag-20Pd-12Au-14.5Cu alloy
      subjected to aging treatment at around 673K is well known, and this hardening has
      been widely employed in various applications. To date, the age-hardening of this
      alloy has been explained to attribute to the precipitation of a beta phase, which
      is a B2-type ordered CuPd phase or PdCuxZn1-x phase. In this study, results
      obtained from microstructural observations using a transmission electron
      microscopy and a scanning transmission electron microscopy revealed that a fine
      L10-type ordered beta' phase precipitated in the matrix and a coarse-structure
      region (consisting of Ag- and Cu-rich regions) appeared after aging treatment at
      673K and contributed to increase in hardness. The microstructure of the coarse
      beta phase, which existed before aging treatment, did not change by aging
      treatment. Thus, it is concluded that the fine beta' phase precipitated by aging
      treatment contributed more to increase in hardness than the coarse-structure
      region and coarse beta phase. 

PMID- 24433920
TI  - In vitro and in vivo degradation evaluation of novel iron-bioceramic composites
      for bone implant applications.
AB  - Biodegradable metals such as magnesium, iron and their alloys have been known as
      potential materials for temporary medical implants. However, most of the studies
      on biodegradable metals have been focusing on optimizing their mechanical
      properties and degradation behavior with no emphasis on improving their
      bioactivity behavior. We therefore investigated the possibility of improving iron
      biodegradation rate and bioactivity by incorporating various bioactive
      bioceramics. The iron-based bioceramic (hydroxyapatite, tricalcium phosphate and
      biphasic calcium phosphate) composites were prepared by mechanical mixing and
      sintering process. Degradation studies indicated that the addition of bioceramics
      lowered the corrosion potential of the composites and slightly increased their
      corrosion rate compared to that of pure iron. In vitro cytotoxicity results
      showed an increase of cellular activity when rat smooth muscle cells interacted
      with the degrading composites compared to pure iron. X-ray radiogram analysis
      showed a consistent degradation progress with that found in vivo and positive
      tissue response up to 70 days implantation in sheep animal model. Therefore, the
      iron-based bioceramic composites have the potential to be used for biodegradable
      bone implant applications.

PMID- 24433921
TI  - Complex cystic breast masses in ultrasound examination.
AB  - Complex cystic masses are defined as lesions composed of anechoic (cystic) and
      echogenic (solid) components, unlike complicated cysts, the echogenic fluid
      content of which imitates a solid lesion. Complex masses are classified as ACR4
      and require histological verification by percutaneous biopsy and/or surgical
      ablation. The etiology is diverse, and can be benign or high risk (an abscess,
      hematoma, fat necrosis, fibrocystic mastopathy, a phyllodes tumor, papilloma) as
      much as malignant (papillary cancer, necrotic cancer, a ductal carcinoma in situ,
      metastases). The biopsy technique must be adapted to each case and it is often
      necessary to insert a coil during the procedure. Histopathological correlation is
      essential to ensure that the samples are representative and concur with the
      ultrasound appearance, so as not to fail to recognize high risk or malignant
      lesions requiring appropriate management. 

PMID- 24433923
TI  - The care model of the future: supporting APRNs through an innovative transition
      to practice program.

PMID- 24433922
TI  - Emerging roles of immunostimulatory oral bacteria in periodontitis development.
AB  - Periodontitis is a common dental disease which results in irreversible alveolar
      bone loss around teeth, and subsequent tooth loss. Previous studies have focused
      on bacteria that damage the host and the roles of commensals to facilitate their
      colonization. Although some immune responses targeting oral bacteria protect the
      host from alveolar bone loss, recent studies show that particular host defense
      responses to oral bacteria can induce alveolar bone loss. Host-damaging and
      immunostimulatory oral bacteria cooperatively induce bone loss by inducing
      gingival damage followed by immunostimulation. In mouse models of experimental
      periodontitis induced by either Porphyromonas gingivalis or ligature, gamma
      proteobacteria accumulate and stimulate host immune responses to induce host
      damage. Here we review the differential roles of individual bacterial groups in
      promoting bone loss through the induction of host damage and immunostimulation. 

PMID- 24433925
TI  - Meticillin-resistant Staphylococcus aureus: spread of specific lineages among
      patients in different wards at a Brazilian teaching hospital.
AB  - This study aimed to characterize meticillin-resistant Staphylococcus aureus
      (MRSA) lineages circulating in a Brazilian teaching hospital. MRSA isolates from
      nasal swabs were evaluated to assess antimicrobial susceptibility, staphylococcal
      cassette chromosome mec (SCCmec), Panton-Valentine leucocidin status, pulsed
      field gel electrophoresis profile and multi-locus sequence type (MLST) analysis.
      Eighty-three MRSA isolates were analysed. SCCmec III (43.4%) and IV (49.4%) were
      predominant. ST1-IV (USA400) was more common in internal medicine (P = 0.002)
      whereas 'clone M' (SCCmec III) was more common in the medical and surgical
      intensive care unit (P = 0.004), and all isolates were ST5-IV (USA800) in
      dermatology (P < 0.001). These data improved the understanding of the MRSA
      epidemiology inside the hospital and helped to establish effective control
      measures.

PMID- 24433924
TI  - Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus
      bacteraemia: role of a cryptic variant of an epidemic clone.
AB  - BACKGROUND: New strains of meticillin-resistant Staphylococcus aureus (MRSA) may
      be associated with changes in rates of disease or clinical presentation.
      Conventional typing techniques may not detect new clonal variants that underlie
      changes in epidemiology or clinical phenotype. AIM: To investigate the role of
      clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in
      England. METHODS: Bacteraemia isolates of the major UK lineages (EMRSA-15 and 
      16) from before and after the outbreak were analysed by whole-genome sequencing
      in the context of epidemiological and clinical data. For comparison, EMRSA-15 and
      -16 isolates from another hospital in England were sequenced. A clonal variant of
      EMRSA-16 was identified at the outbreak hospital and a molecular signature test
      designed to distinguish variant isolates among further EMRSA-16 strains.
      FINDINGS: By whole-genome sequencing, EMRSA-16 isolates during the outbreak
      showed strikingly low genetic diversity (P < 1 * 10(-6), Monte Carlo test),
      compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the
      comparator hospital, demonstrating the emergence of a clonal variant. The variant
      was indistinguishable from the ancestral strain by conventional typing. This
      clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the
      outbreak hospital from 2006. CONCLUSIONS: Evolutionary changes in epidemic MRSA
      strains not detected by conventional typing may be associated with changes in
      disease epidemiology. Rapid and affordable technologies for whole-genome
      sequencing are becoming available with the potential to identify and track the
      emergence of variants of highly clonal organisms.

PMID- 24433926
TI  - Interferon-beta-1a treatment has a positive effect on quality of life of
      relapsing-remitting multiple sclerosis: results from a longitudinal study.
AB  - PURPOSE: The impact of interferon beta (IFNbeta) therapy on a patient's quality
      of life (QoL) has not been completely clarified. This multicenter, independent,
      observational and longitudinal study was aimed to evaluate the impact of
      different pharmaceutical formulations of IFNbeta-1a on QoL in patients affected
      by relapsing-remitting multiple sclerosis (RRMS). METHODS: The multiple sclerosis
      quality of life-54 questionnaire was used to assess patients' QoL. RESULTS: 394
      (66%) patients completed the two-year study; 152 were treated with IFNbeta-1a
      i.m. weekly injected (group a), 152 with IFNbeta-1a 44 MUg s.c. injected three
      times a week (group b) and 90 were untreated (group c). After two years, a
      significant increase was found in the physical health composite score (Delta =
      +3.1 in group a, Delta = +3 in group b, p < 0.05 in both), mental health
      composite score (Delta = +4.7 in group a, Delta = +5.5 in group b, p < 0.001 in
      both), in eight MSQoL sub-items of group a and in seven sub-items in group b.
      Conversely, the untreated group showed a slight decrease in seven domains. The
      variable "therapy with DMDs" was associated with improved QoL. CONCLUSION: QoL of
      RRMS could be improved by IFNbeta-1a treatment, despite natural history data
      which seem to demonstrate that QoL could get worse over the time.

PMID- 24433927
TI  - Docosahexaenoic acid confers enduring neuroprotection in experimental stroke.
AB  - Recently we demonstrated that docosahexaenoic acid (DHA) is highly
      neuroprotective when animals were allowed to survive during one week. This study
      was conducted to establish whether the neuroprotection induced by DHA persists
      with chronic survival. Sprague-Dawley rats underwent 2h of middle cerebral artery
      occlusion (MCAo) and treated with DHA or saline at 3h after MCAo. Animals
      received neurobehavioral examination (composite neuroscore, rota-rod, beam
      walking and Y maze tests) followed by ex vivo magnetic resonance imaging and
      histopathology at 3 weeks. DHA improved composite neurologic score beginning on
      day 1 by 20%, which persisted throughout weeks 1-3 by 24-41% compared to the
      saline-treated group. DHA prolonged the latency in rota-rod on weeks 2-3 by 162
      178%, enhanced balance performance in the beam walking test on weeks 1 and 2 by
      42-51%, and decreased the number of entries in the Y maze test by 51% and
      spontaneous alteration by 53% on week 2 compared to the saline-treated group. DHA
      treatment reduced tissue loss (computed from T2-weighted images) by 24% and total
      and cortical infarct volumes by 46% and 54% compared to the saline-treated group.
      These results show that DHA confers enduring ischemic neuroprotection.

PMID- 24433928
TI  - Brain control of volitional ankle tasks in people with chronic stroke and in
      healthy individuals.
AB  - This study explored the relationships between motor cortical control of ankle
      dorsiflexors and clinical impairments of volitional ankle dorsiflexion in people
      with chronic stroke. Eighteen persons with stroke and 14 controls were evaluated.
      Clinical tools were used to assess ankle dorsiflexion amplitude and isometric
      strength. Transcranial magnetic stimulation (TMS) of the primary motor cortex
      (M1) tested the functional integrity of cortical circuits controlling the
      tibialis anterior (TA). All clinical scores and most TMS outcomes were impaired
      in people with chronic stroke. The lower clinical scores were related to the
      reduction of the strength of corticospinal projections onto spinal motoneurons.
      Concurrent TMS and clinical testing in chronic stroke provided original data
      demonstrating relationships between the integrity of cortical and corticospinal
      components of TA motor control and volitional ankle tasks. Our study proposes
      that volitional ankle mobilization in chronic stroke may be explained by the
      residual abnormal M1 circuits which may be responsive for rehabilitation
      intervention. This should be confirmed in longitudinal studies with larger
      samples to determine whether TMS outcomes associated with lower limb muscles are
      predictive of clinical changes or vice versa. 

PMID- 24433929
TI  - Predictors and impact of the working alliance in the neuropsychological
      rehabilitation of patients with multiple sclerosis.
AB  - BACKGROUND: There is preliminary evidence of positive effects of
      neuropsychological rehabilitation in multiple sclerosis (MS). However, whether a
      working alliance affects rehabilitation outcome has not been studied. OBJECTIVE:
      The aim of this study was to evaluate the effects of the baseline patient-related
      (cognitive, mood and fatigue symptoms, cognitive status, demographic factors) and
      illness-related factors (duration and severity of the disease) on the alliance,
      as well as the effects of the alliance on rehabilitation outcome in
      neuropsychological rehabilitation among MS patients. METHODS: Fifty-six patients
      with relapsing-remitting MS received multimodal neuropsychological intervention
      (attention retraining, learning strategies, psychoeducation, psychological
      support, homework assignments) conducted once a week in 60-minute sessions for
      thirteen consecutive weeks. After the intervention, both patients and therapists
      evaluated the alliance with the short form of the Working Alliance Inventory.
      RESULTS: None of the baseline factors was related to the alliance. Better patient
      evaluated alliance was associated with a more prominent decrease in fatigue
      symptoms and greater achievement of rehabilitation goals. Better therapist
      evaluated alliance was associated with greater benefit from the intervention as
      evaluated by therapists. CONCLUSION: A positive patient-therapist alliance may
      relate to positive neuropsychological rehabilitation outcome in MS.

PMID- 24433930
TI  - The salt stimulation property of serum paraoxonase (PON1) could be a valuable
      factor in evaluating the enzyme status in ischemic stroke: the role of activity
      determined PON1 192Q/R phenotypes.
AB  - Variability in the activity and function of serum paraoxonase (PON1) as an
      antioxidant enzyme involved in vascular disease has been observed. In this study,
      we investigated the enzyme activity parameters, based on the 192Q/R polymorphism,
      using the salt stimulation property of PON1 as an important although neglected
      property. In total, 172 participants, including 90 control subjects and 82
      patients with ischemic stroke were enrolled. Paraoxonase activity (para),
      arylesterase activity (aryl) and salt-stimulated paraoxonase activity (para-Na)
      were measured by spectrophotometric assays. The distribution of the 192Q/R
      phenotypes was determined using the dual substrate method. We observed that the
      para-percent (percentage stimulation of paraoxonase activity by NaCl) was
      significantly lower in the patients than in the controls, in both the QR+RR group
      (p=0.01) and QQ phenotypes (p=0.001). More than the other parameters, para
      percent and para-degree (para-Na-para) are affected by ischemic stroke (p<0.001).
      In R-containing phenotypes, significant correlations were observed between both
      aryl and para, with age (r=-0.364, p=0.016; and r=-0.333, p=0.029, respectively).
      The salt stimulation properties of PON1 activity, particularly the parameters
      para-percent and para-degree, could be considered more important than the
      prevalent activities of the enzyme, and could be better applied for the
      assessment of PON1 status in ischemic stroke rather than the common enzyme
      activities. 

PMID- 24433931
TI  - Non-motor symptoms of Parkinson's disease A review...from the past.
AB  - Although Parkinson's disease (PD) has been classically defined as a motor
      disorder, a range of non-motor symptoms (NMS) including cognitive, mood,
      autonomic and sleep disturbances occur with the passage of time. Although it
      seems that the non-motor aspect of PD is a recent observation, classic authors
      (James Parkinson, Charcot, Gowers, Oppenheim and Wilson) had described many NMS
      including pain, fatigue, bladder dysfunction, cognitive decline and delusion. In
      this review we have collated the classic literature of NMS in PD. 

PMID- 24433932
TI  - Recent advances in acute hearing loss due to posterior circulation ischemic
      stroke.
AB  - Acute hearing loss (AHL) has traditionally been considered to be a neglected and
      underestimated symptom of stroke. However, because the blood supply to the
      auditory system originates from the vertebrobasilar system, stroke in the
      distribution of the vertebrobasilar circulation can present with acute hearing
      loss (AHL) and/or tinnitus. Approximately one-tenth of vertebrobasilar ischemic
      stroke (VBIS) is accompanied by AHL. Sometimes, AHL is a warning symptom of
      impending VBIS (mainly in the anterior inferior cerebellar artery). In this case,
      the MRI is normal, and the clinician must rely on other clinical features to make
      the diagnosis. This review summarizes the current advances in the clinical
      syndromes and signs of AHL due to VBIS. 

PMID- 24433933
TI  - Circadian disruption in the pathogenesis of metabolic syndrome.
AB  - Metabolic syndrome is a multifactorial process induced by a combination of
      genetic and environmental factors and recent evidence has highlighted that
      circadian disruption and sleep loss contribute to disease pathogenesis. Emerging
      work in experimental genetic models has provided insight into the mechanistic
      basis for clock disruption in disease. Indeed, disruption of the clock system
      perturbs both neuroendocrine pathways within the hypothalamus important in
      feeding and energetics, in addition to peripheral tissues involved in glucose and
      lipid metabolism. This review illustrates the impact of molecular clock
      disruptions at the level of both brain and behavior and peripheral tissues, with
      a focus on how such dysregulation in turn impacts lipid and glucose homeostasis,
      inflammation and cardiovascular function. New insight into circadian biology may
      ultimately lead to improved therapeutics for metabolic syndrome and
      cardiovascular disease in humans. 

PMID- 24433934
TI  - A pocket of very high suicide rates in a non-violent, egalitarian and cooperative
      population of South-East Asia.
AB  - BACKGROUND: Extremely high rates of suicide localized within subgroups of
      populations where suicide is rare have been reported. We investigated this
      intriguing observation in a population of South-East Asia, where local culture
      should theoretically be preventative of suicide. METHOD: A team including an
      anthropologist and a psychiatrist surveyed all cases of suicide that had occurred
      over 10 years in four isolated regions. A psychological autopsy was carried out
      comparing each suicide case with two matched control cases. RESULTS: In a region
      of 1192 inhabitants, 16 suicides occurred, leading to an annual suicide rate of
      134/1,000,00 which is 10 times the rate in the USA or Canada. By contrast, three
      ethnically similar distant communities showed low to null rates. The gender ratio
      was three males to one female and two-thirds of cases were aged below 35 years.
      Methods of suicide were poisoning and hanging and motives mainly included
      interpersonal discord. The pattern of developmental and clinical risk factors was
      somewhat different from Western countries, showing no childhood maltreatment,
      only one case of alcohol/substance abuse and impulsive-aggressive personality but
      elevated rates of social anxiety. Suicide cases had very high frequencies of
      second-degree biological relatives who committed suicide. CONCLUSIONS: Our study
      confirms a persistent phenomenon of high suicide rates restricted to a subgroup
      of a pre-industrialized population. We hypothesized this might be explained by
      isolation and endogamy, which may have promoted the selection/amplification of
      genetic vulnerability factors, or a contagion effect. These findings shed light
      on suicide from both a singular and a universal perspective, suggesting that
      particular local conditions may significantly modulate the rate of this complex
      behavior.

PMID- 24433935
TI  - [Appendiceal diverticulitis: A possible diagnosis in acute abdomen].

PMID- 24433936
TI  - The use of Indocyanine green dye angiography in burns.

PMID- 24433937
TI  - Cryopreserved human skin allografts: efficacy and viability.

PMID- 24433938
TI  - Differences between intentional and non-intentional burns in India: implications
      for prevention.
AB  - Non-intentional and deliberate burns in India and other developing countries
      present particular challenges of prevention and treatment. This exploratory study
      sought improved understanding of burns in order to inform treatment and
      prevention. It gathered data in 2011/2012 on burns from the hospital registry
      (N=768) of a government hospital in India and from interviews with women patients
      (N=60) admitted to the burns ward. Analysis indicated that: (1) the conditions
      that facilitate intentional and non-intentional burns are similar, but
      intentional burns involve additional contributory factors; (2) a high proportion
      of patients subjected to burns are young women in domestic situations; and (3) a
      higher proportion of their TBSA was burned, with consequent higher mortality than
      for men. It was concluded that: (1) Haddon's matrix and the situational crime
      prevention framework of criminology assist in understanding the etiology of
      intentional burns and in identifying preventive measures; (2) social service and
      criminal justice agencies have important roles in dealing with victims of
      intentional burns during and after treatment; (3) full account should be taken of
      gender-related physical, psychological and family factors in planning treatment;
      and (4) maintaining careful records of burns cases is vital for estimating the
      prevalence and incidence of intentional injuries. 

PMID- 24433939
TI  - Health related quality of life in burn patients--a review of the literature.
AB  - The burn trauma is multifactorial and involves pathophysiologic processes of all
      of the body's systems. The impact it could have on a person's life includes
      impairments on their esthetic appearance, interpersonal relationships,
      psychological, social and physical functioning. Previously, the outcomes of burn
      care were confined in the context of mortality and length of hospital stay.
      Currently, a shift is afoot from defining good health care as merely the
      reduction of morbidity and mortality to a more holistic approach that involves
      aspects of Health Related Quality of Life. In this article we aim to present a
      concise review of the relevant literature and relevant topics pertaining Health
      Related Quality of Life and burn. 

PMID- 24433940
TI  - Biological markers of stress in pediatric acute burn injury.
AB  - BACKGROUND: Burns and their associated wound care procedures evoke significant
      stress and anxiety, particularly for children. Little is known about the body's
      physiological stress reactions throughout the stages of re-epithelialization
      following an acute burn injury. Previously, serum and urinary cortisol have been
      used to measure stress in burn patients, however these measures are not suitable
      for a pediatric burn outpatient setting. AIM: To assess the sensitivity of
      salivary cortisol and sAA in detecting stress during acute burn wound care
      procedures and to investigate the body's physiological stress reactions
      throughout burn re-epithelialization. METHODS: Seventy-seven participants aged
      four to thirteen years who presented with an acute burn injury to the burn center
      at the Royal Children's Hospital, Brisbane, Australia, were recruited between
      August 2011 and August 2012. RESULTS: Both biomarkers were responsive to the
      stress of burn wound care procedures. sAA levels were on average 50.2 U/ml higher
      (p<0.001) at 10 min post-dressing removal compared to baseline levels. Salivary
      cortisol levels showed a blunted effect with average levels at ten minutes post
      dressing removal decreasing by 0.54 nmol/L (p<0.001) compared to baseline levels.
      sAA levels were associated with pain (p=0.021), no medication (p=0.047) and Child
      Trauma Screening Questionnaire scores at three months post re-epithelialization
      (p=0.008). Similarly, salivary cortisol was associated with no medication
      (p<0.001), pain scores (p=0.045) and total body surface area of the burn
      (p=0.010). CONCLUSION: Factors which support the use of sAA over salivary
      cortisol to assess stress during morning acute burn wound care procedures
      include; sensitivity, morning clinic times relative to cortisol's diurnal peaks,
      and relative cost.

PMID- 24433941
TI  - Mortality and its predictors among antiretroviral therapy naive HIV-infected
      individuals with CD4 cell count >=350 cells/mm(3) compared to the general
      population: data from a population-based prospective HIV cohort in Uganda.
AB  - BACKGROUND: Evidence exists that even at high CD4 counts, mortality among HIV
      infected antiretroviral therapy (ART) naive individuals is higher than that in
      the general population. However, many developing countries still initiate ART at
      CD4 <=350 cells/mm(3). OBJECTIVE: To compare mortality among HIV-infected ART
      naive individuals with CD4 counts >=350 cells/mm(3) with mortality in the general
      Ugandan population and to investigate risk factors for death. DESIGN: Population
      based prospective HIV cohort. METHODS: The study population consisted of HIV
      infected people in rural southwest Uganda. Patients were reviewed at the study
      clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios
      were estimated using Poisson regression. Indirect methods were used to calculate
      standardised mortality ratios (SMRs). RESULTS: A total of 374 participants with
      CD4 >=350 cells/mm(3) were followed for 1,328 person-years (PY) over which 27
      deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95
      29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15
      49 years. Mortality was higher in periods during which participants had CD4 350
      499 cells/mm(3) than during periods of CD4 >=500 cells/mm(3) although the
      difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95%
      CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs
      were 123% higher among participants with CD4 >=500 cells/mm(3) (SMR: 223%, 95%
      CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3)
      (246%, 117%-516). After adjusting for current age, mortality was associated with
      increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95%
      CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories
      <=17.4 Kg/m(2) and >=18.5 Kg/m(2): 6.11, 2.30-16.20). CONCLUSION: HIV-infected
      ART naive individuals with CD4 count >=350 cells/mm(3) had a higher mortality
      than the general population. After adjusting for age, the main predictors of
      mortality were WHO clinical stage and BMI.

PMID- 24433942
TI  - Adoption of routine telemedicine in Norway: the current picture.
AB  - BACKGROUND: Telemedicine appears to be ready for wider adoption. Although
      existing research evidence is useful, the adoption of routine telemedicine in
      healthcare systems has been slow. OBJECTIVE: We conducted a study to explore the
      current use of routine telemedicine in Norway, at national, regional, and local
      levels, to provide objective and up-to-date information and to estimate the
      potential for wider adoption of telemedicine. Design : A top-down approach was
      used to collect official data on the national use of telemedicine from the
      Norwegian Patient Register. A bottom-up approach was used to collect
      complementary information on the routine use of telemedicine through a survey
      conducted at the five largest publicly funded hospitals. RESULTS: Results show
      that routine telemedicine has been adopted in all health regions in Norway and in
      68% of hospitals. Despite being widely adopted, the current level of use of
      telemedicine is low compared to the number of face-to-face visits. Examples of
      routine telemedicine can be found in several clinical specialties. Most services
      connect different hospitals in secondary care, and they are mostly delivered as
      teleconsultations via videoconference. CONCLUSIONS: Routine telemedicine in
      Norway has been widely adopted, probably for geographical reasons, as in other
      settings. However, the level of use of telemedicine in Norway is rather low, and
      it has significant potential for further development as an alternative to face-to
      face outpatient visits. This study is a first attempt to map routine telemedicine
      at regional, institutional, and clinical levels, and it provides useful
      information to understand the adoption of telemedicine in routine healthcare and
      to measure change in future updates.

PMID- 24433943
TI  - Reorienting women's health in low- and middle-income countries: the case of
      depression and Type 2 diabetes.
AB  - Women's health in low- and middle-income countries (LMICs) has historically
      focused on sexual and reproductive health. However, understanding how women
      acquire, experience, and treat non-reproductive health conditions, such as non
      communicable diseases, has become a fundamental public health concern. Special
      attention to the social determinants of LMIC women's health can provide socially
      and culturally relevant knowledge for implementation of policies and programs for
      women increasingly confronting these 'New Challenge Diseases'. This article uses
      the example of depression and Type 2 diabetes comorbidity to illustrate how
      attending to the social determinants of mental and physical health beyond the
      reproductive years contributes to a more holistic agenda for women's health. For
      instance, we must address the plurality of experiences that shape women's health
      from social determinants of depression, such as gendered subjugation within the
      home and public sphere, to the structural determinants of obesity and diabetes,
      such as poor access to healthy foods and health care. Attending to the
      complexities of health and social well-being beyond the reproductive years helps
      the women's global health agenda capture the full spectrum of health concerns,
      particularly the chronic and non-communicable conditions that emerge as life
      expectancy increases. 

PMID- 24433944
TI  - Public and private maternal health service capacity and patient flows in Southern
      Tanzania: using a geographic information system to link hospital and national
      census data.
AB  - BACKGROUND: Strategies to improve maternal health in low-income countries are
      increasingly embracing partnership approaches between public and private
      stakeholders in health. In Tanzania, such partnerships are a declared policy
      goal. However, implementation remains challenging as unfamiliarity between
      partners and insufficient recognition of private health providers prevail. This
      hinders cooperation and reflects the need to improve the evidence base of private
      sector contribution. OBJECTIVE: To map and analyse the capacities of public and
      private hospitals to provide maternal health care in southern Tanzania and the
      population reached with these services. DESIGN: A hospital questionnaire was
      applied in all 16 hospitals (public n=10; private faith-based n=6) in 12
      districts of southern Tanzania. Areas of inquiry included selected maternal
      health service indicators (human resources, maternity/delivery beds), provider
      fees for obstetric services and patient turnover (antenatal care, births).
      Spatial information was linked to the 2002 Population Census dataset and a
      geographic information system to map patient flows and socio-geographic
      characteristics of service recipients. RESULTS: The contribution of faith-based
      organizations (FBOs) to hospital maternal health services is substantial. FBO
      hospitals are primarily located in rural areas and their patient composition
      places a higher emphasis on rural populations. Also, maternal health service
      capacity was more favourable in FBO hospitals. We approximated that 19.9% of
      deliveries in the study area were performed in hospitals and that the proportion
      of c-sections was 2.7%. Mapping of patient flows demonstrated that women often
      travelled far to seek hospital care and where catchment areas of public and FBO
      hospitals overlap. CONCLUSIONS: We conclude that the important contribution of
      FBOs to maternal health services and capacity as well as their emphasis on
      serving rural populations makes them promising partners in health programming.
      Inclusive partnerships could increase integration of FBOs into the public health
      care system and improve coordination and use of scarce resources.

PMID- 24433945
TI  - Associations between mass media exposure and birth preparedness among women in
      southwestern Uganda: a community-based survey.
AB  - BACKGROUND: Exposure to mass media provides increased awareness and knowledge, as
      well as changes in attitudes, social norms and behaviors that may lead to
      positive public health outcomes. Birth preparedness (i.e. the preparations for
      childbirth made by pregnant women, their families, and communities) increases the
      use of skilled birth attendants (SBAs) and hence reduces maternal morbidity and
      mortality. OBJECTIVE: The aim of this study was to explore the association
      between media exposure and birth preparedness in rural Uganda. METHOD: A total of
      765 recently delivered women from 120 villages in the Mbarara District of
      southwest Uganda were selected for a community-based survey using two-stage
      cluster sampling. Univariate and multivariate logistic regression was performed
      with generalized linear mixed models using SPSS 21. RESULTS: We found that 88.6%
      of the women surveyed listened to the radio and 33.9% read newspapers. Birth
      preparedness actions included were money saved (87.8%), identified SBA (64.3%),
      identified transport (60.1%), and purchased childbirth materials (20.7%). Women
      who had taken three or more actions were coded as well birth prepared (53.9%).
      Women who read newspapers were more likely to be birth prepared (adjusted OR 2.2,
      95% CI 1.5-3.2). High media exposure, i.e. regular exposure to radio, newspaper,
      or television, showed no significant association with birth preparedness
      (adjusted OR 1.3, 95% CI 0.9-2.0). CONCLUSION: Our results indicate that
      increased reading of newspapers can enhance birth preparedness and skilled birth
      attendance. Apart from general literacy skills, this requires newspapers to be
      accessible in terms of language, dissemination, and cost.

PMID- 24433946
TI  - Region-wide assessment of the capacity for human nutrition training in West
      Africa: current situation, challenges, and way forward.
AB  - BACKGROUND: There is a dearth of information on existing nutrition training
      programs in West Africa. A preliminary step in the process of developing a
      comprehensive framework to strengthen human capacity for nutrition is to conduct
      an inventory of existing training programs. OBJECTIVE: This study was conducted
      to provide baseline data on university-level nutrition training programs that
      exist in the 16 countries in West Africa. It also aimed to identify existing gaps
      in nutrition training and propose solutions to address them. DESIGN:
      Participating institutions were identified based on information provided by in
      country key informants, UNICEF offices or through internet searches. Data were
      collected through semi-structured interviews during on-site visits or through
      self-administered questionnaires. Simple descriptive and bivariate analyses were
      performed. RESULTS: In total, 83 nutrition degree programs comprising 32 B.Sc.
      programs, 34 M.Sc. programs, and 17 Ph.D. programs were identified in the region.
      More than half of these programs were in Nigeria. Six countries (Cape Verde,
      Guinea-Bissau, Liberia, Mali, The Gambia, and Togo) offered no nutrition degree
      program. The programs in francophone countries were generally established more
      recently than those in anglophone countries (age: 3.5 years vs. 21.4 years).
      Programs were predominantly (78%) run by government-supported institutions. They
      did not provide a comprehensive coverage of all essential aspects of human
      nutrition. They were heavily oriented to food science (46%), with little emphasis
      on public health nutrition (24%) or overnutrition (2%). Annual student intakes
      per program in 2013 ranged from 3 to 262; 7 to 40; and 3 to 10, respectively, for
      bachelor's, master's, and doctoral programs while the number of graduates
      produced annually per country ranged from 6 to 271; 3 to 64; and 1 to 18,
      respectively. External collaboration only existed in 15% of the programs. In
      service training programs on nutrition existed in less than half of the
      countries. The most important needs for improving the quality of existing
      training programs reported were teaching materials, equipment and
      infrastructures, funding, libraries and access to advanced technology resources.
      CONCLUSIONS: There are critical gaps in nutrition training in the West Africa
      region. The results of the present study underscore the urgent need to invest in
      nutrition training in West Africa. An expanded set of knowledge, skills, and
      competencies must be integrated into existing nutrition training curricula. Our
      study provides a basis for the development of a regional strategy to strengthen
      human capacity for nutrition across the region.

PMID- 24433947
TI  - Learning by observation in children with autism spectrum disorder.
AB  - BACKGROUND: Observing another person performing a complex action accelerates the
      observer's acquisition of the same action and limits the time-consuming process
      of learning by trial and error. Learning by observation requires specific skills
      such as attending, imitating and understanding contingencies. Individuals with
      autism spectrum disorder (ASD) exhibit deficits in these skills. METHOD: The
      performance of 20 ASD children was compared with that of a group of typically
      developing (TD) children matched for chronological age (CA), IQ and gender on
      tasks of learning of a visuomotor sequence by observation or by trial and error.
      Acquiring the correct sequence involved three phases: a detection phase (DP), in
      which participants discovered the correct sequence and learned how to perform the
      task; an exercise phase (EP), in which they reproduced the sequence until
      performance was error free; and an automatization phase (AP), in which by
      repeating the error-free sequence they became accurate and speedy. RESULTS: In
      the DP, ASD children were impaired in detecting a sequence by trial and error
      only when the task was proposed as first, whereas they were as efficient as TD
      children in detecting a sequence by observation. In the EP, ASD children were as
      efficient as TD children. In the AP, ASD children were impaired in automatizing
      the sequence. Although the positive effect of learning by observation was
      evident, ASD children made a high number of imitative errors, indicating marked
      tendencies to hyperimitate. CONCLUSIONS: These findings demonstrate the imitative
      abilities of ASD children although the presence of imitative errors indicates an
      impairment in the control of imitative behaviours.

PMID- 24433948
TI  - Effects of computerized physician order entry on medication turnaround time and
      orders requiring pharmacist intervention.
AB  - BACKGROUND: Previous studies have demonstrated that computerized physician order
      entry (CPOE) of prescriptions reduces both turnaround time (TAT) and medication
      errors. However, these studies have been performed primarily in large academic
      centers with a relatively small number of medication orders. As such, many
      studies investigating the impact of CPOE on the level of pharmacist intervention
      have yielded conflicting results. OBJECTIVE: The objective of this study was to
      examine the effects of CPOE on medication order TAT and the frequency of
      medication orders requiring pharmacist intervention in a community-based medical
      center. METHODS: A prospective cohort study was conducted at a community-based
      medical center. A total of 24,767 prescriptions written for 940 patients over a
      six-month period were stratified into CPOE or non-CPOE (handwritten) cohorts. TAT
      between cohorts were tested using analysis of variance and Tukey's Honestly
      Significant Difference test. The number of orders requiring pharmacist
      intervention was compared between cohorts and tested using chi-square test or
      Fisher's exact test. Medication orders requiring pharmacist intervention were
      stratified by patient characteristics, therapeutic class, and types of medication
      error. RESULTS: Medication orders not using CPOE were approximately 8 times more
      likely to require pharmacist intervention (2.26% versus 0.29%; P < 0.001), with
      the majority of pharmacist interventions performed to prevent medication errors.
      The overall mean TAT for medication orders was significantly shorter in the CPOE
      group in comparison with the non-CPOE group (22.2 +/- 86.5 min versus 81 +/-
      256.7 min; P < 0.001). CPOE orders nearly eliminated medication errors with wrong
      dosage forms and formulary issues. CONCLUSIONS: Medication orders entered via
      CPOE are associated with a significant reduction in medication TAT and less
      likely to require pharmacist intervention. Use of CPOE may improve quality of
      patient care and efficiency of health care delivery.

PMID- 24433949
TI  - Dietary and weight-related behaviors and body mass index among Hispanic, Hmong,
      Somali, and white adolescents.
AB  - BACKGROUND: The population of the United States is becoming increasingly
      ethnically and racially diverse, much of it due to immigration patterns. However,
      little is known about dietary intake and weight-related concerns and behaviors of
      youth from some ethnic-minority groups, especially Hispanic, Hmong, and Somali
      adolescents. OBJECTIVE: Our aim was to describe dietary intake and weight-related
      concerns and behaviors among Hispanic, Hmong, and Somali adolescents and compare
      them with white adolescents. DESIGN: We performed a cross-sectional analysis of
      data from Eating and Activity in Teens 2010, a population-based study in the
      Minneapolis/St Paul metropolitan area. PARTICIPANTS/SETTING: Current analysis
      includes 1,672 adolescents (Hispanic: n=562 [33.6%]; Hmong: n=477 [28.5%];
      Somali: n=113 [6.8%]; white: n=520 [31.1%]; mean age=15.0 years). Adolescents
      completed classroom surveys and had their height/weight measured during the 2009
      2010 academic year. STATISTICAL ANALYSIS: Multivariable regression models,
      adjusted for socioeconomic status, age, and school as a random effect were used
      to examine racial/ethnic differences for each outcome variable for boys and
      girls. RESULTS: There were numerous differences in the behaviors of Hispanic,
      Hmong, and Somali adolescents as compared with whites. Hispanic and Somali youth
      consumed fruit and fast food more frequently. Hmong adolescents consumed sugar
      sweetened beverages less frequently, and Somali boys consumed energy and sport
      drinks more frequently than whites. Compared with white boys, overweight/obesity
      was higher among Hispanic and Hmong. A higher percentage of Hmong and Somali
      adolescents engaged in unhealthy weight control behaviors. Body satisfaction was
      lower for all Hmong adolescents compared with whites. CONCLUSIONS: There were
      varying areas of concern in dietary intake, weight, and weight-related concerns
      and behaviors among adolescents in all ethnic groups. Future nutrition and
      physical activity interventions that include adolescents from these ethnic and
      cultural groups can benefit from, for example, modifying intervention strategies
      to the specific priority behaviors within the target population.

PMID- 24433950
TI  - Defining acute ischemic stroke tissue pathophysiology with whole brain CT
      perfusion.
AB  - BACKGROUND: This study aimed to identify and validate whole brain perfusion
      computed tomography (CTP) thresholds for ischemic core and salvageable penumbra
      in acute stroke patients and develop a probability based model to increase the
      accuracy of tissue pathophysiology measurements. METHODS: One hundred and eighty
      three patients underwent multimodal stroke CT using a 320-slice scanner within
      6hours of acute stroke onset, followed by 24hour MRI that included diffusion
      weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging
      (PWI). Coregistered acute CTP and 24hour DWI was used to identify the optimum
      single perfusion parameter thresholds to define penumbra (in patients without
      reperfusion), and ischemic core (in patients with reperfusion), using a pixel
      based receiver operator curve analysis. Then, these results were used to develop
      a sigma curve fitted probability based model incorporating multiple perfusion
      parameter thresholds. RESULTS: For single perfusion thresholds, a time to peak
      (TTP) of +5seconds best defined the penumbra (area under the curve, AUC 0.79 CI
      0.74-0.83) while a cerebral blood flow (CBF) of < 50% best defined the acute
      ischemic core (AUC 0.73, CI 0.69-0.77). The probability model was more accurate
      at detecting the ischemic core (AUC 0.80 SD 0.75-0.83) and penumbra (0.85 SD 0.83
      0.87) and was significantly closer in volume to the corresponding reference DWI
      (P=0.031). CONCLUSIONS: Whole brain CTP can accurately identify penumbra and
      ischemic core using similar thresholds to previously validated 16 or 64 slice
      CTP. Additionally, a novel probability based model was closer to defining the
      ischemic core and penumbra than single thresholds.

PMID- 24433951
TI  - Pure endoscopic expanded endonasal approach for olfactory groove and tuberculum
      sellae meningiomas.
AB  - The expanded endoscopic endonasal (EEE) approach for the removal of olfactory
      groove (OGM) and tuberculum sellae (TSM) meningiomas is currently becoming an
      acceptable surgical approach in neurosurgical practice, although it is still
      controversial with respect to its outcomes, indications and limitations. Here we
      provide a review of the available literature reporting results with use of the
      EEE approach for these lesions together with our experience with the use of the
      endoscope as the sole means of visualization in a series of patients with no
      prior surgical biopsy or resection. Surgical cases between May 2006 and January
      2013 were retrospectively reviewed. Twenty-three patients (OGM n=6; TSM n=17)
      were identified. In our series gross total resection (GTR) was achieved in 4/6
      OGM (66.7%) and 11/17 (64.7%) TSM patients. Vision improved in the OGM group
      (2/2) and 8/11 improved in the TSM group with no change in visual status in the
      remaining three patients. Post-operative cerebrospinal fluid (CSF) leak occurred
      in 2/6 (33%) OGM and 2/17 (11.8%) TSM patients. The literature review revealed a
      total of 19 OGM and 174 TSM cases which were reviewed. GTR rate was 73% for OGM
      and 56.3% for TSM. Post-operative CSF leak was 30% for OGM and 14% for TSM. With
      careful patient selection and a clear understanding of its limitations, the EEE
      technique is both feasible and safe. However, longer follow-ups are necessary to
      better define the appropriate indications and ideal patient population that will
      benefit from the use of these newer techniques. 

PMID- 24433952
TI  - [Differential diagnosis of local tumor recurrence or radionecrosis after
      stereotactic radiosurgery for treatment of brain metastasis].
AB  - Magnetic resonance imaging (MRI) is a method of choice for follow-up of
      irradiated brain metastasis. It is difficult to differentiate local tumour
      recurrences from radiation induced-changes in case of suspicious contrast
      enhancement. New advanced MRI techniques (perfusion and spectrometry) and amino
      acid positron-emission tomography (PET) allow to be more accurate and could avoid
      a stereotactic biopsy for histological assessment, the only reliable but invasive
      method. We report the case of a patient who underwent surgery for a single, left
      frontal brain metastasis of a breast carcinoma, followed by adjuvant stereotactic
      radiotherapy in the operative bed. Seven months after, she presented a local
      change in the irradiated area on the perfusion-weighted MRI, for which the
      differentiation between a local tumour recurrence and radionecrosis was not
      possible. PET with 2-deoxy-((18)F)-fluoro-D-glucose (FDG) revealed a
      hypermetabolic lesion. After surgical resection, the histological assessment has
      mainly recovered radionecrosis with few carcinoma cells. The multimodal MRI has
      greatly contributed to refine the differential diagnosis between tumour
      recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in
      favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion
      is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve
      interest but are not available in all centres. Stereotactic biopsy should be
      discussed if any doubt remains. 

PMID- 24433953
TI  - Transcatheter aortic valve replacement for isolated aortic valve insufficiency:
      experience with the Engager valve.

PMID- 24433954
TI  - Statins can induce myasthenia gravis.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      statins, are commonly prescribed for prevention of cardiovascular morbidity. A
      rare side effect of statin medication is the induction of autoimmune illnesses,
      including myasthenia gravis (myasthenia). Here we present two patients with
      seropositive myasthenia that developed 4 weeks after initiation of atorvastatin,
      increasing the total reported patients to seven. Reviewing recent literature we
      highlight the connections between statins, auto-immunity and myasthenia. Statins
      may favour T-cell phenotypes that reduce cell-mediated immunity but could
      increase antibody-mediated humoral immunity.

PMID- 24433955
TI  - Epigenetic targeting in pancreatic cancer.
AB  - The prognosis of pancreatic cancer patients is very poor, with a 5-year survival
      of less than 6%. Therefore, there is an urgent need for new therapeutic options
      in pancreatic cancer. In the past years it became evident that deregulation of
      epigenetic mechanisms plays an important role in pancreatic carcinogenesis. This
      review focuses on the exploitation of drugs that alter histone modifications, DNA
      methylation and microRNA expression as options for the treatment of pancreatic
      cancer. 

PMID- 24433956
TI  - Genetic and environmental analysis of dystocia and stillbirths in draft horses.
AB  - Genetic parameters and environmental factors were estimated for foaling ease (FE)
      and stillbirths (SBs) in four breeds of draft horses based on 11 229, 38 877, 35
      764 and 13 274 FE and SB scores recorded between 1998 and 2010 for Ardennais (A),
      Breton (B), Comtois (C) and Percheron (P), respectively. Incidences for the three
      FE categories were: easy or without help 91.0% (A) to 95.4% (B), difficult 3.4%
      (B) to 7.1% (A) and intervention of a veterinarian 1.1% (B) to 1.9% (A). The
      frequency of SB ranged between 5.4% (B) and 9.4% (A). A multiple-trait threshold
      animal model was used that included the effects of sex of foal, region, month,
      year of foaling, combined maternal age and parity, direct genetic, maternal
      genetic and permanent environments. Estimates were obtained using Markov Chain
      Monte Carlo Gibbs sampling. The most unfavourable effect was first parity, which
      decreased the probability of easy foaling to 78.6% for A and 88.3% for B.
      Interaction with age showed that the risk for first foaling for mares aged 3
      years was higher than at 4 or 5 to 9 years. This was also observed for SB with an
      increased probability of SB at first foaling of 17.9% (A) or 9.6% (B). The most
      unfavourable month was found to be the most frequent month for foaling (April)
      and not the most demanding months weather-wise (winter). For FE, direct
      heritabilities were A 0.27 (0.06), B 0.14 (0.03), C 0.18 (0.03) and P 0.18
      (0.04), and maternal heritabilities were A 0.25 (0.06), B 0.19 (0.04), C 0.12
      (0.03) and P 0.21 (0.06). Genetic correlations between direct and maternal
      genetic effects were A -0.29 (0.14), B -0.39 (0.12), C -0.09 (0.14) and P -0.54
      (0.17). For SB, direct heritabilities were A 0.52 (0.09), B 0.42 (0.04), C 0.28
      (0.04) and P 0.39 (0.05), and maternal heritabilities were A 0.25 (0.05), B 0.10
      (0.02), C 0.07 (0.02) and P 0.14 (0.02). Genetic correlations between direct and
      maternal genetic effects were A -0.85 (0.06), B -0.63 (0.06), C -0.64 (0.11) and
      P -0.69 (0.06). Direct genetic correlations between FE and SB traits were A 0.60
      (0.10), B 0.58 (0.10), C 0.36 (0.10) and P 0.29 (0.15). Maternal genetic
      correlations between FE and SB traits were A 0.67 (0.10), B 0.47 (0.13), C 0.28
      (0.15) and P 0.39 (0.15). These estimates are posterior means of the Gibbs
      samples and are within the upper limits of comparable results reported in cattle.

PMID- 24433957
TI  - Genetic diversity and differentiation of 12 eastern Adriatic and western Dinaric
      native sheep breeds using microsatellites.
AB  - Nuclear genetic diversity and differentiation of 341 sheep belonging to 12 sheep
      breeds from Croatia and Bosnia and Herzegovina were examined. The aim of the
      study was to provide the understanding of the genetic structure and variability
      of the analysed pramenka sheep populations, and to give indications for
      conservation strategies based on the population diversity and structure
      information. The genetic variation of the sheep populations, examined at the
      nuclear level using 27 microsatellite loci, revealed considerable levels of
      genetic diversity, similar to the diversity found in other European indigenous
      low-production sheep breeds. Population-specific alleles were detected at most
      loci and in breeds analysed. The observed heterozygosity ranged from 0.643 (in
      Lika pramenka) to 0.743 (in Vlasic pramenka), and the expected heterozygosity
      ranged from 0.646 (in Lika pramenka) to 0.756 (in Dalmatian pramenka).
      Significant inbreeding coefficients were found for half of the populations
      studied and ranged from 0.040 (Pag island sheep) to 0.091 (Kupres pramenka).
      Moderate genetic differentiation was found between the studied sheep populations.
      The total genetic variability observed between different populations was 5.29%,
      whereas 94.71% of the variation was found within populations. Cres island sheep,
      Lika pramenka and Istrian sheep were identified as the most distinct populations,
      which was confirmed by the factorial analysis of correspondence and supported
      through a bootstrapping adjustment to correct for the difference in the sample
      sizes. The population structure analysis distinguished 12 clusters for the 12
      sheep breeds analysed. However, the cluster differentiation was low for
      Dalmatian, Vlasic, Stolac and Krk pramenka. This systematic study identified Lika
      pramenka and Rab island sheep as those with the lowest diversity, whereas Istrian
      sheep and Pag island sheep had the highest. Conservation actions are proposed for
      Istrian, Rab and Cres island sheep, Lika and Kupres pramenka because of high
      estimated coefficients of inbreeding.

PMID- 24433958
TI  - Predictive ability of selected subsets of single nucleotide polymorphisms (SNPs)
      in a moderately sized dairy cattle population.
AB  - Several studies have shown that computation of genomic estimated breeding values
      (GEBV) with accuracies significantly greater than parent average (PA) estimated
      breeding values (EBVs) requires genotyping of at least several thousand progeny
      tested bulls. For all published analyses, GEBV computed from the selected samples
      of markers have lower or equal accuracy than GEBV derived on the basis of all
      valid single nucleotide polymorphisms (SNPs). In the current study, we report on
      four new methods for selection of markers. Milk, fat, protein, somatic cell
      score, fertility, persistency, herd life and the Israeli selection index were
      analyzed. The 972 Israeli Holstein bulls genotyped with EBV for milk production
      traits computed from daughter records in 2012 were assigned into a training set
      of 844 bulls with progeny test EBV in 2008, and a validation set of 128 young
      bulls. Numbers of bulls in the two sets varied slightly among the nonproduction
      traits. In EFF12, SNPs were first selected for each trait based on the effects of
      each marker on the bulls' 2012 EBV corrected for effective relationships, as
      determined by the SNP matrix. EFF08 was the same as EFF12, except that the SNPs
      were selected on the basis of the 2008 EBV. In DIFmax, the SNPs with the greatest
      differences in allelic frequency between the bulls in the training and validation
      sets were selected, whereas in DIFmin the SNPs with the smallest differences were
      selected. For all methods, the numbers of SNPs retained varied over the range of
      300 to 6000. For each trait, except fertility, an optimum number of markers
      between 800 and 5000 was obtained for EFF12, based on the correlation between the
      GEBV and current EBV of the validation bulls. For all traits, the difference
      between the correlation of GEBV and current EBV and the correlation of the PA and
      current EBV was >0.25. EFF08 was inferior to EFF12, and was generally no better
      than PA EBV. DIFmax always outperformed DIFmin and generally outperformed EFF08
      and PA. Furthermore, GEBV based on DIFmax were generally less biased than PA. It
      is likely that other methods of SNP selection could improve upon these results. 

PMID- 24433959
TI  - Maternal backfat depth in gestating sows has a greater influence on offspring
      growth and carcass lean yield than maternal feed allocation during gestation.
AB  - A commercial pig spends nearly half of its life in utero and its nutrition during
      this time can influence birth weight and postnatal growth. We hypothesised that
      postnatal growth is increased in pigs raised by sows with a high backfat depth
      and high level of energy intake during gestation compared with sows with a low
      backfat depth and low level of energy intake during gestation. This was tested in
      a 2 * 3 factorial design experiment with 2 factors for gilt backfat depth (Thin
      and Fat) and 3 factors for gestation feed allowance (Restricted, Control and
      High). Between d 25 and d 90 of gestation, Thin gilts (n=68; 12 +/- 0.6 mm P2
      backfat) and Fat gilts (n=72; 19 +/- 0.6 mm P2 backfat) were randomly allocated,
      as individuals, to a gestation diet (6.19 g/kg lysine, 13.0 MJ DE/kg) at the
      following feed allowances: 1.8 kg/day (Restricted); 2.5 kg/day (Control) and 3.5
      kg/day (High). For the remainder of gestation and during lactation all gilts were
      treated similarly. At weaning (day 28), 155 piglets were sacrificed and 272 were
      individually housed and followed through to slaughter (day 158). At day 80 of
      gestation, fasted Thin Restricted gilts had lower serum IGF-1 concentrations than
      Thin High or Thin Control fed gilts (P<0.001). Pigs born from Fat gilts had
      greater backfat depths (P<0.05), a lower lean meat yield (P<0.05) and were
      heavier (P<0.05) at slaughter than pigs born from Thin gilts. Gilt gestation feed
      allowance had only transitory effects on average daily gain and feed conversion
      efficiency and had no effect on pig weight at slaughter (P>0.05) or lean meat
      yield (P>0.05). In conclusion, gilts with a backfat depth of ~19 mm at
      insemination produced pigs that were heavier and fatter at ~158 days of age than
      those born from gilts with ~12 mm backfat depth at insemination. Maternal body
      condition during gestation had a more predominant influence on growth parameters
      of the offspring, such as weight at slaughter and backfat depth, than did feed
      level during gestation.

PMID- 24433960
TI  - Apparent digestibility of broken rice in horses using in vivo and in vitro
      methods.
AB  - The aim of this study was to assess the apparent digestibility of broken rice
      using total collection of feces and the pepsin-cellulase in vitro technique to
      provide updated and more accurate digestion coefficients for this by-product when
      fed to horses. The in vivo digestibility trial was consecutively performed, using
      five adult geldings, weighing 555.6 kg on average. First, hay was given as the
      only feedstuff, while second, the experimental diet consisted of the same hay
      plus broken rice at a forage-to-concentrate ratio of 70/30 (on dry matter (DM)
      basis). Feces were collected over 6 days preceded by a 14-day adaptation period.
      The digestibility trial was carried out to determine the digestion coefficients
      for DM, organic matter (OM), CP and gross energy in both diets, while apparent
      digestion coefficients for the same parameters were calculated for broken rice
      alone, using the difference between the two sets of results. At the same time, an
      in vitro trial was carried out using pepsin-cellulase technique on the samples of
      hay and broken rice tested during the in vivo trial. As expected, supplementation
      with broken rice increased digestibility according to all the parameters used.
      The high OM digestion coefficients of broken rice were confirmed both by the
      calculated in vivo method and by the predicted results of pepsin-cellulase
      technique (92.6% and 87.1%, respectively), underlining the high digestibility of
      this by-product when fed to horses. 

PMID- 24433961
TI  - Food restriction enhances oxidative status in aging rats with neuroprotective
      effects on myenteric neuron populations in the proximal colon.
AB  - Food restriction may slow the aging process by increasing the levels of
      antioxidant defenses and reducing cell death. We evaluated the effects of food
      restriction on oxidative and nutritional status, myenteric cell populations, and
      the colonic muscle layer in aging rats. Wistar rats were distributed into control
      groups (7, 12, and 23months of age) and subjected to food restriction (50% of
      normal diet) beginning at 7months of age. The animals were sacrificed, and blood
      was collected to evaluate its components and markers of oxidative status,
      including thiobarbituric acid-reactive substances, reduced glutathione, catalase,
      glutathione peroxidase, and total antioxidant capacity. The proximal colon was
      collected to evaluate HuC/D and neuronal nitric oxide synthase (nNOS)-positive
      and -negative myenteric neurons, S-100 glial cells, and the muscle layer. Age
      negatively affected oxidative status in the animals, which also increased the
      levels of total cholesterol, protein, and globulins and increased the thickness
      of the muscle layer. Aging also reduced the number and hypertrophied glial cell
      bodies, HuC/D neurons, and nNOS-negative and -positive neurons. An improvement
      was observed in oxidative status and the levels of total cholesterol and
      triglycerides with food restriction, which also provided neuroprotection of the
      intrinsic innervation. However, food restriction accentuated the loss of enteric
      glia and caused hypertrophy in the muscle layer at 23months. Food restriction
      improved oxidative and nutritional status in rats and protected HuC/D neurons and
      nNOS-negative and -positive neurons against neuronal loss. Nevertheless, food
      restriction caused morphoquantitative changes in glial cell populations, with
      possible interference with colonic neuromuscular control. 

PMID- 24433962
TI  - Direct synthesis of C3-mono-functionalized oxindoles from N-unprotected 2
      oxindole and their antileishmanial activity.
AB  - A novel approach for the synthesis of unprecedented C3-mono-functionalized
      indolin-2-ones is reported, starting from 2-oxindole and chalcones. The reactions
      proceed regioselectively under mild conditions, without di- and tri-alkylated
      side products. The new compounds have been evaluated in vitro for their
      antiproliferative effects against the protozoan Leishmania infantum.
      Interestingly, they appear able to kill L. infantum promastigotes and
      amastigotes, without significant cytotoxic effects. 

PMID- 24433964
TI  - Structure-activity relationships of substituted oxyoxalamides as inhibitors of
      the human soluble epoxide hydrolase.
AB  - We explored both structure-activity relationships among substituted oxyoxalamides
      used as the primary pharmacophore of inhibitors of the human sEH and as a
      secondary pharmacophore to improve water solubility of inhibitors. When the
      oxyoxalamide function was modified with a variety of alkyls or substituted
      alkyls, compound 6 with a 2-adamantyl group and a benzyl group was found to be a
      potent sEH inhibitor, suggesting that the substituted oxyoxalamide function is a
      promising primary pharmacophore for the human sEH, and compound 6 can be a novel
      lead structure for the development of further improved oxyoxalamide or other
      related derivatives. In addition, introduction of substituted oxyoxalamide to
      inhibitors with an amide or urea primary pharmacophore produced significant
      improvements in inhibition potency and water solubility. In particular, the N,N,O
      trimethyloxyoxalamide group in amide or urea inhibitors (26 and 31) was most
      effective among those tested for both inhibition and solubility. The results
      indicate that substituted oxyoxalamide function incorporated into amide or urea
      inhibitors is a useful secondary pharmacophore, and the resulting structures will
      be an important basis for the development of bioavailable sEH inhibitors. 

PMID- 24433963
TI  - Microtubule-stabilizing agents as potential therapeutics for neurodegenerative
      disease.
AB  - Microtubules (MTs), cytoskeletal elements found in all mammalian cells, play a
      significant role in cell structure and in cell division. They are especially
      critical in the proper functioning of post-mitotic central nervous system
      neurons, where MTs serve as the structures on which key cellular constituents are
      trafficked in axonal projections. MTs are stabilized in axons by the MT
      associated protein tau, and in several neurodegenerative diseases, including
      Alzheimer's disease, frontotemporal lobar degeneration, and Parkinson's disease,
      tau function appears to be compromised due to the protein dissociating from MTs
      and depositing into insoluble inclusions referred to as neurofibrillary tangles.
      This loss of tau function is believed to result in alterations of MT structure
      and function, resulting in aberrant axonal transport that likely contributes to
      the neurodegenerative process. There is also evidence of axonal transport
      deficiencies in other neurodegenerative diseases, including amyotrophic lateral
      sclerosis and Huntington's disease, which may result, at least in part, from MT
      alterations. Accordingly, a possible therapeutic strategy for such
      neurodegenerative conditions is to treat with MT-stabilizing agents, such as
      those that have been used in the treatment of cancer. Here, we review evidence of
      axonal transport and MT deficiencies in a number of neurodegenerative diseases,
      and summarize the various classes of known MT-stabilizing agents. Finally, we
      highlight the growing evidence that small molecule MT-stabilizing agents provide
      benefit in animal models of neurodegenerative disease and discuss the desired
      features of such molecules for the treatment of these central nervous system
      disorders. 

PMID- 24433965
TI  - Small molecule mimetics of an interferon-alpha receptor interacting domain.
AB  - Small molecules that mimic IFN-alpha epitopes that interact with the cell surface
      receptor, IFNAR, would be useful therapeutics. One such 8-amino acid region in
      IFN-alpha2, designated IRRP-1, was used to derive 11 chemical compounds that
      belong to 5 distinct chemotypes, containing the molecular features represented by
      the key residues Leu30, Arg33, and Asp35 in IRRP-1. Three of these compounds
      exhibited potential mimicry to IRRP-1 and, in cell based assays, as predicted,
      effectively inhibited IFNAR activation by IFN-alpha. Of these, compound 3 did not
      display cell toxicity and reduced IFN-alpha-inducible STAT1 phosphorylation and
      STAT-DNA binding. Based on physicochemical properties' analyses, our data suggest
      that moieties with acidic pKa on the small molecule may be a necessary element
      for mimicking the carboxyl group of Asp35 in IRRP-1. Our data confirm the
      relevance of this strategy of molecular mimicry of ligand-receptor interaction
      domains of protein partners for small molecule drug discovery. 

PMID- 24433966
TI  - Synthesis of quercetin glycosides and their melanogenesis stimulatory activity in
      B16 melanoma cells.
AB  - 4'-O-beta-d-Glucopyranosyl-quercetin-3-O-beta-d-glucopyranosyl-(1->4)-beta-d
      glucopyra-noside (3) was isolated from Helminthostachys zeylanica root extract as
      a melanogenesis acceleration compound and was synthesized using rutin as the
      starting material. Related compounds were also synthesized to understand the
      structure-activity relationships in melanin biosynthesis. Melanogenesis
      activities of the glycosides were determined by measuring intracellular melanin
      content in B16 melanoma cells. Among the synthesized quercetin glycosides,
      quercetin-3-O-beta-d-glucopyranoside (1), quercetin-3-O-beta-d-glucopyranosyl-(1
      >4)-beta-d-glucopyranoside (2), and 3 showed more potent intracellular
      melanogenesis acceleration activities than theophyline used as positive control
      in a dose-dependent manner with no cytotoxic effect. 

PMID- 24433967
TI  - Synthesis, biophysical characterization and anti-HIV activity of d(TG3AG)
      Quadruplexes bearing hydrophobic tails at the 5'-end.
AB  - Novel conjugated G-quadruplex-forming d(TG3AG) oligonucleotides, linked to
      hydrophobic groups through phosphodiester bonds at 5'-end, have been synthesized
      as potential anti-HIV aptamers, via a fully automated, online phosphoramidite
      based solid-phase strategy. Conjugated quadruplexes showed pronounced anti-HIV
      activity with some preference for HIV-1, with inhibitory activity invariably in
      the low micromolar range. The CD and DSC monitored thermal denaturation studies
      on the resulting quadruplexes, indicated the insertion of lipophilic residue at
      the 5'-end, conferring always improved stability to the quadruplex complex
      (20<DeltaTm<40 degrees C). The data suggest no direct functional relationship
      between the thermal stability and anti-HIV activity of the folded conjugated G
      quartets. It would appear that the nature of the residue at 5' end of the
      d(TG3AG) quadruplexes plays an important role in the thermodynamic stabilization
      but a minor influence on the anti-HIV activity. Moreover, a detailed CD and DSC
      analyses indicate a monophasic behaviour for sequences I and V, while for ODNs
      (II-IV) clearly show that these quadruplex structures deviate from simple two
      state melting, supporting the hypothesis that intermediate states along the
      dissociation pathway may exist. 

PMID- 24433968
TI  - Distribution and morphology of calcitonin gene-related peptide and substance P
      immunoreactive axons in the whole-mount atria of mice.
AB  - The murine model has been used to investigate the role of cardiac sensory axons
      in various disease states. However, the distribution and morphological structures
      of cardiac nociceptive axons in normal murine tissues have not yet been well
      characterized. In this study, whole-mount atria from FVB mice were processed with
      calcitonin gene-related peptide (CGRP) and substance P (SP) primary antibodies
      followed by secondary antibodies, and then examined using confocal microscopy. We
      found: 1) Large CGRP-IR axon bundles entered the atria with the major veins, and
      these large bundles bifurcated into small bundles and single axons that formed
      terminal end-nets and free endings in the epicardium. Varicose CGRP-IR axons had
      close contacts with muscle fibers, and some CGRP-IR axons formed varicosities
      around principle neurons (PNs) within intrinsic cardiac ganglia (ICGs). 2) SP-IR
      axons also were found in the same regions of the atria, attached to veins, and
      within cardiac ganglia. Similar to CGRP-IR axons, these SP-IR axons formed
      terminal end-nets and free endings in the atrial epicardium and myocardium.
      Within ICGs, SP-IR axons formed varicose endings around PNs. However, SP-IR nerve
      fibers were less abundant than CGRP-IR fibers in the atria. 3) None of the PNs
      were CGRP-IR or SP-IR. 4) CGRP-IR and SP-IR often colocalized in terminal
      varicosities around PNs. Collectively, our data document the distribution pattern
      and morphology of CGRP-IR and SP-IR axons and terminals in different regions of
      the atria. This knowledge provides useful information for CGRP-IR and SP-IR axons
      that can be referred to in future studies of pathological remodeling. 

PMID- 24433969
TI  - Geographic atrophy: clinical features and potential therapeutic approaches.
AB  - In contrast to wet age-related macular degeneration (AMD), where loss of vision
      is typically acute and treatment leads to a relatively rapid reduction in retinal
      fluid and subsequent improvements in visual acuity (VA), disease progression and
      vision loss in geographic atrophy (GA) owing to AMD are gradual processes.
      Although GA can result in significant visual function deficits in reading, night
      vision, and dark adaptation, and produce dense, irreversible scotomas in the
      visual field, the initial decline in VA may be relatively minor if the fovea is
      spared. Because best-corrected VA does not correlate well with GA lesions or
      progression, alternative clinical endpoints are being sought. These include
      reduction in drusen burden, slowing the enlargement rate of GA lesion area, and
      slowing or eliminating the progression of intermediate to advanced AMD. Among
      these considerations, slowing the expansion of the GA lesion area seems to be a
      clinically suitable primary efficacy endpoint. Because GA lesion growth is
      characterized by loss of photoreceptors, it is considered a surrogate endpoint
      for vision loss. Detection of GA can be achieved with a number of different
      imaging techniques, including color fundus photography, fluorescein angiography,
      fundus autofluorescence (FAF), near-infrared reflectance, and spectral-domain
      optical coherence tomography. Previous studies have identified predictive
      characteristics for progression rates including abnormal patterns of FAF in the
      perilesional retina. Although there is currently no approved or effective
      treatment to prevent the onset and progression of GA, potential therapies are
      being evaluated in clinical studies. 

PMID- 24433970
TI  - Outcomes of changing immunosuppressive therapy after treatment failure in
      patients with noninfectious uveitis.
AB  - PURPOSE: To evaluate the outcomes of changing immunosuppressive therapy for
      noninfectious uveitis after failure. DESIGN: Retrospective cohort study.
      PARTICIPANTS: Patients with noninfectious uveitis managed at 2 tertiary uveitis
      clinics in the United Kingdom and Australia. METHODS: Participants with a history
      of using immunosuppressive therapy were identified in clinics, and notes were
      reviewed by doctors trained in uveitis therapy. Each treatment episode/course
      (starting or changing a therapy) was identified, and demographic details,
      clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or
      biologicals), and drug doses were obtained. MAIN OUTCOME MEASURES: For each
      treatment episode, the reasons for changing therapy, corticosteroid-sparing
      effects, and control of inflammation were determined. RESULTS: A total of 147
      patients were identified who underwent 309 different treatment episodes. Fifty
      five percent of patients eventually required a change in treatment after their
      first treatment episode/course. Forty-five episodes involved switching from one
      ISA to another, with 50% to 100% of these patients achieving "success"
      (prednisolone <=10 mg and sustained control) with the new ISA. A combination of
      ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of
      these patients. Biological agents were used in 45 episodes, the most common one
      being infliximab, which achieved success in 80% of patients. CONCLUSIONS: Our
      data suggest that control of inflammation can be achieved after switching or
      combining ISAs.

PMID- 24433971
TI  - Use of health care claims data to study patients with ophthalmologic conditions.
AB  - OBJECTIVE: To describe what information is or is not included in health care
      claims data, provide an overview of the main advantages and limitations of
      performing analyses using health care claims data, and offer general guidance on
      how to report and interpret findings of ophthalmology-related claims data
      analyses. DESIGN: Systematic review. PARTICIPANTS: Not applicable. METHODS: A
      literature review and synthesis of methods for claims-based data analyses. MAIN
      OUTCOME MEASURES: Not applicable. RESULTS: Some advantages of using claims data
      for analyses include large, diverse sample sizes, longitudinal follow-up, lack of
      selection bias, and potential for complex, multivariable modeling. The
      disadvantages include (a) the inherent limitations of claims data, such as
      incomplete, inaccurate, or missing data, or the lack of specific billing codes
      for some conditions; and (b) the inability, in some circumstances, to adequately
      evaluate the appropriateness of care. In general, reports of claims data analyses
      should include clear descriptions of the following methodological elements: the
      data source, the inclusion and exclusion criteria, the specific billing codes
      used, and the potential confounding factors incorporated in the multivariable
      models. CONCLUSIONS: The use of claims data for research is expected to increase
      with the enhanced availability of data from Medicare and other sources. The use
      of claims data to evaluate resource use and efficiency and to determine the basis
      for supplementary payment methods for physicians is anticipated. Thus, it will be
      increasingly important for eye care providers to use accurate and descriptive
      codes for billing. Adherence to general guidance on the reporting of claims data
      analyses, as outlined in this article, is important to enhance the credibility
      and applicability of findings. Guidance on optimal ways to conduct and report
      ophthalmology-related investigations using claims data will likely continue to
      evolve as health services researchers refine the metrics to analyze large
      administrative data sets.

PMID- 24433972
TI  - Qualitative and quantitative characteristics of near-infrared autofluorescence in
      diabetic macular edema.
AB  - OBJECTIVE: To study the characteristics of near-infrared autofluorescence (NIR
      AF) imaging and its association with spectral-domain optical coherence tomography
      (SD-OCT) findings and logarithm of the minimal angle of resolution (logMAR)
      visual acuity (VA) in diabetic macular edema (DME). DESIGN: Retrospective,
      observational, cross-sectional study. PARTICIPANTS: One hundred twenty-one
      consecutive eyes of 87 patients with center-involved DME for whom NIR-AF and SD
      OCT images of sufficient quality were obtained. METHODS: The NIR-AF images were
      acquired using Heidelberg Retina Angiograph 2 (Heidelberg Engineering,
      Heidelberg, Germany), and sectional retinal images were obtained using Spectralis
      OCT (Heidelberg Engineering). The presence of a mosaic pattern and cystoid signs
      were determined qualitatively. We quantified the average fluorescence intensity
      in the central 1-mm subfield. The characteristics of the NIR-AF images were
      compared with the OCT findings and logMAR VA. MAIN OUTCOME MEASURES: Qualitative
      and quantitative characteristics of the NIR-AF images and their association with
      SD-OCT findings and logMAR VA. RESULTS: Fifty-seven eyes with a mosaic pattern in
      the NIR-AF macular images had worse logMAR VA (0.355+/-0.239 vs. 0.212+/-0.235; P
      = 0.001), a thicker central subfield (CSF) (530+/-143 MUm vs. 438+/-105 MUm; P
      <0.001), and disrupted external limiting membrane (ELM; P <0.001) compared with
      64 eyes without these findings. Forty-one eyes with a cystoid sign in the NIR-AF
      images had worse logMAR VA (0.393+/-0.233 vs. 0.221+/-0.234; P <0.001) and a
      thicker CSF (557+/-155 MUm vs. 443+/-100 MUm; P <0.001) than those without them;
      there were no significant differences in the ELM status. The relative
      fluorescence intensity in the central subfield in the NIR-AF images was
      correlated negatively with the CSF thickness and logMAR VA (R = 0.492, P <0.001
      and R = 0.377, P <0.001, respectively). Eyes with foveal serous retinal
      detachment had lower levels of relative fluorescence intensity than those without
      it (0.751+/-0.191 vs. 0.877+/-0.154; P = 0.007); there was no association with
      the presence of foveal cystoid spaces, disrupted ELM, or hyperreflective foci in
      the outer retinal layers. CONCLUSIONS: Novel qualitative and quantitative NIR-AF
      characteristics in the macula indicated the clinical relevance and suggested the
      pathogenesis in DME.

PMID- 24433973
TI  - Predictors of matching in ophthalmology residency for international medical
      graduates.

PMID- 24433974
TI  - Utility of cell block in the cytological preoperative diagnosis of keratocystic
      odontogenic tumor.
AB  - In most cases involving jaw lesions, a biopsy and a histopathological analysis
      are necessary to establish the final diagnosis. However, biopsy may be a complex
      procedure at some maxillomandibular sites, and some systemic conditions could
      contraindicate the procedure. Thus, a search for new, less invasive techniques,
      which could eventually replace biopsy and simplify the diagnostic process, would
      benefit both professionals and patients. The aim of this study was to evaluate
      the cell block technique, prepared from the aspiration of luminal contents, in
      the preoperative diagnosis of keratocystic odontogenic tumors (KCOT). From 135
      cases of lesions aspirated and processed by the cell block technique, we selected
      those containing keratin. In all cases selected, histological diagnosis was based
      on surgical biopsy. From 20 cases containing keratin in the cytological analyses,
      19 were KCOTs and one was an orthokeratinized odontogenic cyst (OOC). In all KCOT
      cases, we observed the presence of parakeratin, even in those with intense
      inflammation. In the cytological analysis of the OOC, parakeratin was not
      observed. In conclusion, there is strong evidence that KCOT can be confidently
      diagnosed preoperatively by cytological analyses of lesions punctured and
      processed by the cell block technique. 

PMID- 24433975
TI  - Solid state and sonochemical syntheses of nano lead(II) chloride and bromide
      coordination polymers from its nitrate analog via mechanochemical crystal to
      crystal transformations.
AB  - Reversible crystal-to-crystal transformations of 3D lead(II) coordination
      polymers with the ligand 2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene (4-bpdh),
      from nitrate analoge [Pb(4-bpdh)(NO3)2(H2O)]n (1) to [Pb(4-bpdh)(NO3)(Br)]n (2),
      [Pb(4-bpdh)(Br)2]n (3), [Pb(4-bpdh)(NO3)(Cl)]n (4) and [Pb(4-bpdh)(Cl)2]n (5) by
      solid state anion-replacement processes under mechanochemical reactions, have
      been studied. The reversible solid state structural transformations of compounds
      1-5, by anion-replacement processes under mechanochemical reaction, have been
      verified by PXRD measurements. Nanoparticles of compounds were synthesized by
      sonochemical process and characterized by scanning electron microscopy (SEM),
      powder X-ray diffraction, IR spectroscopy and elemental analyses. The SEM images
      showed that morphology change occurs during solid state anion-replacements of
      nanocrystals.

PMID- 24433976
TI  - Synchrotron radiation X-ray imaging of cavitation bubbles in Al-Cu alloy melt.
AB  - Cavitation bubbles in Al-10 wt.%Cu melt has been investigated by adopting
      synchrotron radiation X-ray imaging technology. In-situ observation reveals that
      most of bubbles concentrate within an intense cavitation zone nearby the
      radiation face. The measured near-maximum bubble radii obey a similar truncated
      Gaussian distribution as in water but increase by nearly the magnitude of one
      order due to higher ultrasonic intensity applied in aluminum melt.

PMID- 24433977
TI  - Eating to stop: tyrosine supplementation enhances inhibitory control but not
      response execution.
AB  - Animal studies and research in humans have shown that the supplementation of
      tyrosine, or tyrosine-containing diets, increase the plasma tyrosine and enhance
      brain dopamine (DA). However, the strategy of administering tyrosine (and the
      role of DA therein) to enhance cognition is unclear and heavily debated. We
      studied, in a healthy population, whether tyrosine supplementation improves
      stopping overt responses, a core cognitive-control function. In a double-blind,
      placebo-controlled, within-subject design, one hour following the administration
      of tyrosine (corresponding to the beginning of the 1h-peak of the plasma
      concentration) or placebo, participants performed a stop-signal task-which taps
      into response inhibition and response execution speed. Participants in the
      Tyrosine condition were more efficient in inhibiting unwanted action tendencies
      but not in reacting to go signals. This is the first demonstration that the
      supplementation of tyrosine selectively targets, and reliably improves the
      ability to stop overt responses. 

PMID- 24433978
TI  - Association between multilayer left ventricular rotational mechanics and the
      development of left ventricular remodeling after acute myocardial infarction.
AB  - BACKGROUND: The identification of patients at risk for developing left
      ventricular (LV) remodeling after acute myocardial infarction (AMI) has crucial
      prognostic implications. The aims of this study were (1) to investigate the
      relationship between peak subepicardial and subendocardial twist and infarct
      transmurality, as assessed using contrast-enhanced magnetic resonance imaging,
      and (2) to evaluate the association between peak subepicardial and subendocardial
      twist and LV remodeling 6 months after AMI. METHODS: A total of 213 patients with
      ST-segment elevation AMIs who underwent three-dimensional echocardiography for LV
      volumes and functional assessment and two-dimensional speckle-tracking analysis
      for the evaluation of LV twist (subendocardial vs subepicardial) were
      retrospectively included. A subgroup of 40 patients underwent magnetic resonance
      imaging within 2 months for infarct size quantification. RESULTS: Peak
      subepicardial twist was strongly related to infarct size (number of segments with
      transmural scar: r(2) = 0.526, P < .001; total scar score: r(2) = 0.515, P <
      .001) compared with peak subendocardial twist (number of segments with transmural
      scar: r(2) = 0.379, P < .001; total scar score: r(2) = 0.331, P < .001). In the
      overall population, 44 patients (21%) developed significant LV remodeling at 6
      month follow-up (LV end-systolic volume increase >= 15%). These patients showed
      significantly more impaired peak subepicardial and subendocardial twist at
      baseline compared with patients without LV remodeling (4.5 +/- 1.3 degrees  vs
      9.4 +/- 3.5 degrees , P < .001; 7.0 +/- 3.2 degrees  vs 12.9 +/- 5.8 degrees , P
      < .001, respectively). Importantly, peak subepicardial twist (odds ratio, 0.241;
      95% confidence interval, 0.134-0.431; P < .001) and peak troponin T (odds ratio,
      1.152; 95% confidence interval, 1.006-1.320; P = .041) were independently
      associated with the development of LV remodeling. CONCLUSIONS: Peak subepicardial
      twist strongly reflects infarct transmurality as assessed with magnetic resonance
      imaging and is independently associated with LV remodeling after AMI.

PMID- 24433979
TI  - Development and evaluation of methodologies for teaching focused cardiac
      ultrasound skills to medical students.
AB  - BACKGROUND: Handheld ultrasound is emerging as an important tool for point-of
      care cardiac assessment. Although cardiac ultrasound skills are traditionally
      introduced during postgraduate training, the optimal time and methodology to
      initiate training in focused cardiac ultrasound (FCU) are unknown. The objective
      of this study was to develop and evaluate a novel curriculum for training medical
      students in the use of FCU. METHODS: The study was conducted in two phases. In
      the first phase, 12 first-year medical students underwent FCU training over an 8
      week period. In the second phase, 45 third-year medical students were randomized
      to one of three educational programs. Program 1 consisted of a lecture-based
      approach with scan training by a sonographer. Program 2 coupled electronic
      education modules with sonographer scan training. Program 3 was fully self
      directed, combining electronic modules with scan training on a high-fidelity
      ultrasound simulator. Image interpretation skills and scanning technique were
      evaluated after each program. RESULTS: First-year medical students were able to
      modestly improve interpretation ability and acquire limited scanning skills.
      Third-year medical students exhibited similar improvement in mean examination
      score for image interpretation whether a lecture-based program or electronic
      modules was used. Students in the self-directed group using an ultrasound
      simulator had significantly lower mean quality scores than students taught by
      sonographers. CONCLUSIONS: Third-year medical students were able to acquire FCU
      image acquisition and interpretation skills after a novel training program. Self
      directed electronic modules are effective for teaching introductory FCU
      interpretation skills, while expert-guided training is important for developing
      scanning technique.

PMID- 24433980
TI  - Quantum dot-based assay for Cu(2+) quantification in bacterial cell culture.
AB  - A simple and sensitive method for quantification of nanomolar copper with a
      detection limit of 1.2*10(-10)M and a linear range from 10(-9) to 10(-8)M is
      reported. For the most useful analytical concentration of quantum dots,
      1160MUg/ml, a 1/Ksv value of 11MUM Cu(2+) was determined. The method is based on
      the interaction of Cu(2+) with glutathione-capped CdTe quantum dots (CdTe-GSH
      QDs) synthesized by a simple and economic biomimetic method. Green CdTe-GSH QDs
      displayed the best performance in copper quantification when QDs of different
      sizes/colors were tested. Cu(2+) quantification is highly selective given that no
      significant interference of QDs with 19 ions was observed. No significant effects
      on Cu(2+) quantification were determined when different reaction matrices such as
      distilled water, tap water, and different bacterial growth media were tested. The
      method was used to determine copper uptake kinetics on Escherichia coli cultures.
      QD-based quantification of copper on bacterial supernatants was compared with
      atomic absorption spectroscopy as a means of confirming the accuracy of the
      reported method. The mechanism of Cu(2+)-mediated QD fluorescence quenching was
      associated with nanoparticle decomposition. 

PMID- 24433981
TI  - Stroke in community-acquired bacterial meningitis: a Danish population-based
      study.
AB  - OBJECTIVES: Stroke is a serious complication in community-acquired bacterial
      meningitis (CABM), but the incidence, predispositions, and outcome need further
      clarification; this pertains in particular to the impact of pre-existing
      atherosclerosis risk factors. Therefore, we aimed to assess these features in a
      retrospective population-based cohort study. METHODS: We included all patients
      over 16 years of age with CABM in North Denmark Region, 1998-2010. All data were
      retrieved from the patient records. A Glasgow Outcome Scale score of 1-4 was
      defined as an unfavourable outcome and 5 as favourable. RESULTS: We identified
      152 episodes of CABM. In 22 (14%) of the episodes, the patient had a stroke; 15
      strokes were ischaemic, three were haemorrhagic, and four were a combination of
      both. Age and atherosclerosis risk factors were not significantly associated with
      stroke. However, stroke was associated with a higher in-hospital mortality (27%
      vs. 16%; age adjusted risk ratio (age aj. RR) 1.43, 95% confidence interval (CI)
      0.67-3.04), unfavourable outcome (86% vs. 37%; age adj. RR 2.09, 95% CI 1.59
      2.75), and long-term sequelae among survivors (88% vs. 40%, age adj. RR 2.01, 95%
      CI 1.53-2.65) compared with patients without stroke. CONCLUSIONS: Stroke is a
      common complication among adult CABM patients and is associated with long-term
      sequelae and possibly also death. However, stroke seemed not to be related to
      atherosclerosis risk factors.

PMID- 24433982
TI  - Splenic abscess due to brucellosis: a case report and a review of the literature.
AB  - Splenic abscess due to acute brucellosis is a rare event. We report a case of
      multiple splenic abscesses caused by Brucella melitensis in a 45-year-old woman
      and review the English language literature based on a PubMed/MEDLINE search of
      the last 50 years. The majority of the cases published in the literature were due
      to B. melitensis and a splenectomy was required in half of the cases. Antibiotics
      alone without surgical intervention can be successful in the treatment of
      patients with splenic brucellosis in the early stages of the disease. 

PMID- 24433983
TI  - The vulnerability of men to virologic failure during antiretroviral therapy in a
      public routine clinic in Burkina Faso.
AB  - INTRODUCTION: Gender differences in antiretroviral therapy (ART) outcomes are
      critical in sub-Saharan Africa. We assessed the association between gender and
      virologic failure among adult patients treated in a public routine clinic (one of
      the largest in West Africa) in Burkina Faso. METHODS: We performed a case-control
      study between July and October 2012 among patients who had received ART at the
      Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or
      older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six
      months. Cases were all patients with two consecutive HIV loads >1000 copies/mL
      (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL
      associated with immunologic or clinical failure criteria. Controls were all
      patients who only had HIV loads <300 copies/mL. The association between gender
      and virologic failure was assessed using a multivariate logistic regression,
      adjusted on age, level of education, baseline CD4+ T cell count, first and
      current antiretroviral regimens and time on ART. RESULTS: Of 2303 patients (74.2%
      women; median age: 40 years; median time on ART: 34 months), 172 had virologic
      failure and 2131 had virologic success. Among the former, 130 (75.6%) had
      confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four
      (2.3%) had viro-clinical failure. The proportion of men was significantly higher
      among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to
      controls, cases were also younger, more immunodeficient at ART initiation, less
      likely to receive a protease inhibitor-based antiretroviral regimen and had spent
      a longer period of time on ART. After adjustment, male gender remained strongly
      associated with virologic failure (odds ratio 2.52, 95% CI: 1.77-3.60; p<0.001).
      CONCLUSIONS: Men on ART appeared more vulnerable to virologic failure than women.
      Additional studies are needed to confirm the poorer prognosis of men in this
      setting and to determine the causes for their vulnerability in order to optimize
      HIV care. From now on, efforts should be made to support the adherence of men to
      ART in the African setting.

PMID- 24433984
TI  - High prevalence of low bone mass and associated factors in Korean HIV-positive
      male patients undergoing antiretroviral therapy.
AB  - INTRODUCTION: Low bone mass is prevalent in HIV-positive patients. However,
      compared to Western countries, less is known about HIV-associated osteopenia in
      Asian populations. METHODS: We performed a cross-sectional survey in Seoul
      National University Hospital from December 2011 to May 2012. We measured bone
      mineral density using central dual energy X-ray absorptiometry, with consent, in
      male HIV-positive patients, aged 40 years and older. Diagnosis of low bone mass
      was made using International Society for Clinical Densitometry Z-score criteria
      in the 40-49 years age group and World Health Organization T-score criteria in
      the >50-year age group. The data were compared with those of a community-based
      cohort in Korea. RESULTS: Eighty-four HIV-positive male patients were included in
      this study. Median age was 49 (interquartile range [IQR], 45-56) years, and
      median body mass index (BMI) was 22.6 (IQR, 20.9-24.4). Viral suppression was
      achieved in 75 (89.3%) patients and median duration of antiretroviral therapy was
      71 (IQR, 36-120) months. The overall prevalence of low bone mass was 16.7% in the
      40-49 years age group and 54.8% in the>50 years age group. Our cohort had
      significantly lower bone mass at the femur neck and total hip than HIV-negative
      Koreans in the 40-49 years age group. Low bone mass was significantly associated
      with low BMI, and a high level of serum carboxy-terminal collagen crosslinks, but
      was not associated with antiretroviral regimen or duration of antiretroviral
      therapy. CONCLUSIONS: Low bone mass is prevalent in Korean HIV-positive males
      undergoing antiretroviral therapy, and may be associated with increased bone
      resorption.

PMID- 24433985
TI  - Exome analysis of HIV patients submitted to dendritic cells therapeutic vaccine
      reveals an association of CNOT1 gene with response to the treatment.
AB  - INTRODUCTION: With the aim of searching genetic factors associated with the
      response to an immune treatment based on autologous monocyte-derived dendritic
      cells pulsed with autologous inactivated HIV, we performed exome analysis by
      screening more than 240,000 putative functional exonic variants in 18 HIV
      positive Brazilian patients that underwent the immune treatment. METHODS: Exome
      analysis has been performed using the ILLUMINA Infinium HumanExome BeadChip.
      zCall algorithm allowed us to recall rare variants. Quality control and SNP
      centred analysis were done with GenABEL R package. An in-house implementation of
      the Wang method permitted gene-centred analysis. RESULTS: CCR4-NOT transcription
      complex, subunit 1 (CNOT1) gene (16q21), showed the strongest association with
      the modification of the response to the therapeutic vaccine (p=0.00075). CNOT1
      SNP rs7188697 A/G was significantly associated with DC treatment response. The
      presence of a G allele indicated poor response to the therapeutic vaccine
      (p=0.0031; OR=33.00; CI=1.74-624.66), and the SNP behaved in a dominant model
      (A/A vs. A/G+G/G p=0.0009; OR=107.66; 95% CI=3.85-3013.31), being the A/G
      genotype present only in weak/transient responders, conferring susceptibility to
      poor response to the immune treatment. DISCUSSION: CNOT1 is known to be involved
      in the control of mRNA deadenylation and mRNA decay. Moreover, CNOT1 has been
      recently described as being involved in the regulation of inflammatory processes
      mediated by tristetraprolin (TTP). The TTP-CCR4-NOT complex (CNOT1 in the CCR4
      NOT complex is the binding site for TTP) has been reported as interfering with
      HIV replication, through post-transcriptional control. Therefore, we can
      hypothesize that genetic variation occurring in the CNOT1 gene could impair the
      TTP-CCR4-NOT complex, thus interfering with HIV replication and/or host immune
      response. CONCLUSIONS: Being aware that our findings are exclusive to the 18
      patients studied with a need for replication, and that the genetic variant of
      CNOT1 gene, localized at intron 3, has no known functional effect, we propose a
      novel potential candidate locus for the modulation of the response to the immune
      treatment, and open a discussion on the necessity to consider the host genome as
      another potential variant to be evaluated when designing an immune therapy study.

PMID- 24433986
TI  - Cognitive performance and convulsion risk after experimentally-induced febrile
      seizures in rat.
AB  - Many reports indicated that small percentage of children with febrile seizures
      develop epilepsy and cognitive disorders later in adulthood. In addition, the
      neuronal network of the hippocampus was reported to be deranged in adult animals
      after being exposed to hyperthermia-induced seizures in their neonatal life. The
      aims of this study were to investigate (1) latency and probability of seizures,
      (2) spatial learning and memory, in adult rats after neonatal hyperthermia
      induced febrile seizures (FS). Prolonged FS were elicited in 10-day old, male
      Sprague Dawleys (n=11/group) by exposure to heated air (48-52  degrees C) for 30
      min; control rats were exposed to 30  degrees C air. After 1.5 months the
      animal's cognitive performance was assessed by 5 day trial in the Morris water
      maze. In another experiment the latency and probability of seizures were measured
      in response to pentylenetetrazole (PTZ) injections (increased doses ranged from 7
      to 140 mg/kg; i.p.). In water maze, both groups showed improvements in escape
      latency and distance swam to reach the platform; effects were significantly
      greater in control versus hyperthermia-treated animals on days 3 and 4. Latency
      and probability of PTZ-induced seizures were shorter and higher respectively, in
      hyperthermia-treated animals compared to controls. We concluded that FS in
      neonatal rats leads to enhanced susceptibility for seizures, as well as cognitive
      deficits in adults.

PMID- 24433988
TI  - [Misoprostol: off-label use in the first trimester of pregnancy (spontaneous
      abortion, and voluntary medical termination of pregnancy)].
AB  - OBJECTIVE: State of knowledge about misoprostol's use out of its marketing
      authorization during the first trimester of pregnancy, in early miscarriage or to
      induce abortion or medical termination of pregnancy. METHODS: French and English
      publications were searched using PubMed, Cochrane Library and international
      learned societies recommendations. RESULTS: Cervical ripening prior to surgical
      uterine evacuation during the first trimester of pregnancy facilitates cervical
      dilatation and reduces operative time and uterine retention risk. Misoprostol,
      mifepristone and osmotic cervical dilators are equally efficient. Concerning
      first trimester miscarriage, surgical uterine evacuation remains the most
      effective and the quickest method of treatment (EL 1). Depending on the clinical
      situation, medical treatment using misoprostol (missed miscarriage) or
      expectative attitude (incomplete miscarriage) does not increase the risk of
      complications, neither haemorrhagic nor infectious (EL 1). However, these
      alternatives generally require longer outpatient follow-up, which leads to more
      consultations, prolonged bleeding and not planned surgical procedures (EL 1).
      Concerning missed miscarriage, a vaginal dose of 800 MUg of misoprostol, possibly
      repeated 24 to 48 hours later, seems to offer the best efficiency/tolerance ratio
      (EL 2). Concerning early abortion, medical method is a safe and efficient
      alternative to surgery (EL 2). Success rates are inversely proportional to
      gestational age (EL 2). According to the modalities of its marketing
      authorization, 400 MUg of misoprostol can only be given by oral route, for less
      than 7 weeks of amenorrhea (WA) pregnancies and after 36 to 48 hours following
      600 mg of mifepristone (EL 1). However, 200mg of mifepristone is as efficient as
      600 mg (EL 1). Beyond 7WA, misoprostol buccal dissolution (sublingual or
      prejugal) or vaginal administration are more efficient and better tolerated than
      oral ingestion (EL 1). Between 7 and 9WA, the best protocol in terms of
      efficiency and tolerance is the association of 200mg of mifepristone followed 24
      to 48 hours later by 800 MUg of vaginal, sublingual or buccal misoprostol (EL 1).
      An additional dose of 400 MUg can be given 3 hours later if necessary (EL 3). In
      case of buccal administration, the dose of 400 MUg seems to offer the same
      efficiency with a better tolerance but further evaluation is needed (EL 2).
      Between 9 and 12WA, medical treatment is less efficient than surgery and its
      tolerance is lower (EL 2). However, a protocol of 200mg of mifepristone followed
      36 to 48 hours later by 800 MUg of vaginal or sublingual misoprostol, plus an
      additional 400 MUg dose every 3-4 hours (until 4-5 doses maximum) seems safe and
      efficient (EL 5). CONCLUSION: Misoprostol use during the first trimester of
      pregnancy is a safe and efficient alternative to surgery as long as detailed
      protocols adjusted to each clinical situation are respected.

PMID- 24433989
TI  - [Cervical ripening with misoprostol with a live fetus].
AB  - OBJECTIVES: To evaluate the effectiveness and safety of misoprostol for cervical
      ripening or induction of labor at term. METHODS: A critical review of studies
      identified from searches of PubMed and the Cochrane libraries using the following
      keywords: "misoprostol", "cervical ripening", "epidemiology", "pregnancy
      outcome", "maternal morbidity", "perinatal death". RESULTS: Vaginal misoprostol
      in doses of 25 MUg three- to six-hourly was similar as dinoprostone in
      effectiveness (caesarean section rate or vaginal delivery in 24 hours) (LE1) and
      risks (uterine hyperstimulation, adverse neonatal outcome, uterine rupture,
      maternal side-effects) (LE1). Published medico-economic studies are not
      sufficient to evaluate a potential profit to the use of vaginal misoprostol 25
      MUg (Avis d'Experts). The use of misoprostol in women with prior cesarean
      delivery or major uterine surgery has been associated with an increase in uterine
      rupture and therefore should be avoided (LE4). CONCLUSIONS: Review of the current
      literature favors the use of vaginal misoprostol 25 MUg three- to six-hourly
      equally to dinoprostone accordingly with previous French and international
      guidelines (World Health Organization and American College of Obstetricians and
      Gynecologist). The use of misoprostol 25 MUg supposes a preparation by the
      pharmacist to ensure the safety of this precise posology. Medico-economic studies
      are warranted to attest an economic profit to the use of misoprostol 25 MUg in
      comparison to dinoprostone.

PMID- 24433987
TI  - Roles for TNF-receptor associated factor 3 (TRAF3) in lymphocyte functions.
AB  - TRAF3 is an adapter protein that serves and regulates the functions of several
      types of receptors, located both inside the cell and at the plasma membrane.
      These include members of the TNF receptor superfamily (TNFR-SF), toll-like
      receptors (TLR), and cytokine receptors. It has become increasingly evident that
      the roles and functions of TRAF3 are highly context-dependent. TRAF3 can serve
      distinct roles for different receptors in the same cell, and also has highly cell
      type-dependent functions. This review focuses upon the current state of knowledge
      regarding how TRAF3 regulates the biology and effector functions of B and T
      lymphocytes, two major cell types of the adaptive immune response in which TRAF3
      has markedly distinct roles. 

PMID- 24433990
TI  - [Use of misoprostol in gynaecology].
AB  - OBJECTIVES: To assess the interest of misoprostol in gynaecology and particularly
      for cervical priming. METHOD: Research in PubMed in English and French about
      misoprostol and its use in gynaecology. RESULTS: We summarized the results of 3
      meta-analyses, randomized controlled trials and literature review. Results show
      that misoprostol did not scientifically prove a benefit for cervical priming
      before hysteroscopy or before intra-uterine device (IUD). Results are the same
      with post-menopausal or nulliparous women. It did not lead either to lower the
      complications but increase adverse effects. CONCLUSION: It is not indicated to
      use misoprostol for cervical priming in gynaecology.

PMID- 24433991
TI  - Feasibility study on pinhole camera system for online dosimetry in boron neutron
      capture therapy.
AB  - The feasibility of a pinhole camera system for online dosimetry in boron neutron
      capture therapy (BNCT) was studied. A prototype system was designed and built.
      Prompt gamma-rays from the (10)B(n,alpha)(7)Li reaction from a phantom irradiated
      with neutrons were detected with the prototype system. An image was reconstructed
      from the experimental data. The reconstructed image showed a good separation of
      the two borated regions in the phantom. The counting rates and signal-to-noise
      ratio when using the system in actual BNCT applications are also discussed. 

PMID- 24433992
TI  - Interaction of Bothrops jararaca venom metalloproteinases with protein
      inhibitors.
AB  - Snake venom metalloproteinases (SVMPs) play important roles in the local and
      systemic hemorrhage observed upon envenomation. In a previous study on the
      structural elements important for the activities of HF3 (highly hemorrhagic, P
      III-SVMP), bothropasin (hemorrhagic, P-III-SVMP) and BJ-PI (non-hemorrhagic, P-I
      SVMP), from Bothrops jararaca, it was demonstrated that they differ in their
      proteolysis profile of plasma and extracellular matrix proteins. In this study,
      we evaluated the ability of proteins DM43 and alpha2-macroglobulin to interfere
      with the proteolytic activity of these SVMPs on fibrinogen and collagen VI and
      with their ability to induce hemorrhage. DM43 inhibited the proteolytic activity
      of bothropasin and BJ-PI but not that of HF3, and was not cleaved the three
      proteinases. On the other hand, alpha2-macroglobulin did not inhibit any of the
      proteinases and was rather cleaved by them. In agreement with these findings,
      binding analysis showed interaction of bothropasin and BJ-PI but not HF3 to DM43
      while none of the proteinases bound to alpha2-macroglobulin. Moreover, DM43
      promoted partial inhibition of the hemorrhagic activity of bothropasin but not
      that of HF3. Our results demonstrate that metalloproteinases of B. jararaca venom
      showing different domain composition, glycosylation level and hemorrhagic potency
      show variable susceptibilities to protein inhibitors. 

PMID- 24433993
TI  - Pelvic radiculopathies, lumbosacral plexopathies, and neuropathies in oncologic
      disease: a multidisciplinary approach to a diagnostic challenge.
AB  - The purpose of this article is to familiarize the reader with the anatomy of the
      major pelvic nerves and the clinical features of associated lumbosacral
      plexopathies. To demonstrate this we illustrate several cases of malignant
      lumbosacral plexopathy on computed tomography, magnetic resonance imaging, and
      positron emission tomography/computed tomography. A new lumbosacral plexopathy in
      a patient with a prior history of abdominal or pelvic malignancy is usually of
      malignant etiology. Biopsies may be required to definitively differentiate tumour
      from posttreatment fibrosis, and in cases of inconclusive sampling or where
      biopsies are not possible, follow-up imaging may be necessary. In view of the
      complexity of clinical findings often confounded by a history of prior surgery
      and/or radiotherapy, a multidisciplinary approach between oncologists,
      neurologists, and radiologists is often required for what can be a diagnostic
      challenge. 

PMID- 24433994
TI  - [Elevation of cardiac biomarkers in an elderly patient: beyond the acute coronary
      syndrome].

PMID- 24433995
TI  - Antiproliferative effects of carbon monoxide on pancreatic cancer.
AB  - BACKGROUND: Carbon monoxide, the gaseous product of heme oxygenase, is a
      signalling molecule with a broad spectrum of biological activities. The aim of
      this study was to investigate the effects of carbon monoxide on proliferation of
      human pancreatic cancer. METHODS: In vitro studies were performed on human
      pancreatic cancer cells (CAPAN-2, BxPc3, and PaTu-8902) treated with a carbon
      monoxide-releasing molecule or its inactive counterpart, or exposed to carbon
      monoxide gas (500 ppm/24h). For in vivo studies, pancreatic cancer cells (CAPAN
      2/PaTu-8902) were xenotransplanted subcutaneously into athymic mice, subsequently
      treated with carbon monoxide-releasing molecule (35 mg/kg b.w. i.p./day), or
      exposed to safe doses of carbon monoxide (500 ppm 1h/day; n = 6 in each group).
      RESULTS: Both carbon monoxide-releasing molecule and carbon monoxide exposure
      significantly inhibited proliferation of human pancreatic cancer cells (p<0.05).
      A substantial decrease in Akt phosphorylation was observed in carbon monoxide
      releasing molecule compared with inactive carbon monoxide-releasing molecule
      treated cancer cells (by 30-50%, p<0.05). Simultaneously, carbon monoxide
      releasing molecule and carbon monoxide exposure inhibited tumour proliferation
      and microvascular density of xenotransplanted tumours (p<0.01), and doubled the
      survival rates (p<0.005). Exposure of mice to carbon monoxide led to an almost 3
      fold increase in carbon monoxide content in tumour tissues (p=0.006). CONCLUSION:
      These data suggest a new biological function for carbon monoxide in
      carcinogenesis, and point to the potential chemotherapeutic/chemoadjuvant use of
      carbon monoxide in pancreatic cancer.

PMID- 24433996
TI  - Laparoscopic liver resections in normal and cirrhotic livers: a retrospective
      analysis in a tertiary hepato-biliary unit.
AB  - BACKGROUND: Liver surgery in patients with underlying liver disease results in
      higher mortality and morbidity rates compared to patients without underlying
      liver disease. Laparoscopy seems to have good results in patients with normal
      liver in terms of postoperative outcomes, but is more challenging in cirrhotic
      patients. Aim of this study was to evaluate the feasibility of laparoscopic liver
      resection both in normal and cirrhotic livers, and secondary endpoint was to
      compare the surgical results. METHODS: We retrospectively evaluated 105 patients
      who underwent laparoscopic liver resection between November 2001 and January
      2012. Candidates for laparoscopic liver resection were divided into two groups
      according to the presence or absence of an underlying liver disease. RESULTS: 105
      patients (52.4% males, median age 56.1 years) were enrolled, and 37.1% had liver
      cirrhosis. Hepatocellular carcinoma in hepatitis C virus-related cirrhosis
      (89.7%) and liver metastases (57.6%) were the main indications for surgery in
      patients with cirrhosis and non-cirrhotic livers, respectively. None of the
      patients died post-operatively. Cirrhotic patients had greater blood loss (100 vs
      50 ml; p<0.012) and longer hospital stays (6 vs 4 days; p<0.031) compared to non
      cirrhotics. CONCLUSIONS: Laparoscopic liver resections are safe and feasible
      procedures in both patients with cirrhotic and non-cirrhotic livers.

PMID- 24433997
TI  - Acute variceal haemorrhage in the United Kingdom: patient characteristics,
      management and outcomes in a nationwide audit.
AB  - BACKGROUND: Despite advances in treatment, acute variceal haemorrhage remains
      life-threatening. AIM: To describe contemporary characteristics, management and
      outcomes of patients with cirrhosis and acute variceal haemorrhage and risk
      factors for rebleeding and mortality. METHODS: Multi-centre clinical audit
      conducted in 212 UK hospitals. RESULTS: In 526 cases of acute variceal
      haemorrhage, 66% underwent endoscopy within 24h with 64% (n=339) receiving
      endoscopic therapy. Prior to endoscopy, 57% (n=299) received proton pump
      inhibitors, 44% (n=232) vasopressors and 27% (n=144) antibiotics. 73% (n=386)
      received red cell transfusion, 35% (n=184) fresh frozen plasma and 14% (n=76)
      platelets, with widely varying transfusion thresholds. 26% (n=135) experienced
      further bleeding and 15% (n=80) died by day 30. The Model for End Stage Liver
      Disease score was the best predictor of mortality (area under the receiver
      operating curve=0.74, P<0.001). Neither the clinical nor full Rockall scores were
      useful predictors of outcome. Coagulopathy was strongly associated with
      rebleeding (odds ratio 2.23, 95% CI 1.22-4.07, P=0.01, up to day 30) and
      mortality (odds ratio 3.06, 95% CI 1.29-7.26, P=0.01). CONCLUSIONS: Although
      mortality has improved following acute variceal haemorrhage, rebleeding rates
      remain appreciably high. There are notable deficiencies in the use of
      vasopressors and endoscopic therapy. More work is needed to understand the
      optimum transfusion strategies. Better risk stratification tools are required to
      identify patients needing more intensive support.

PMID- 24433998
TI  - Physiological responses of the seagrass Thalassia hemprichii (Ehrenb.) Aschers as
      indicators of nutrient loading.
AB  - To select appropriate bioindicators for the evaluation of the influence of
      nutrients from human activities in a Thalassia hemprichii meadow, environmental
      variables and plant performance parameters were measured in Xincun Bay, Hainan
      Island, South China. Nutrient concentrations in the bay decreased along a
      gradient from west to southeast. Moreover, the nutrients decreased with an
      increase in the distance from the shore on the southern side of the bay. Among
      the candidate indicators, the P content of the tissues closely mirrored the two
      nutrient loading gradients. The epiphytic algae biomass and the N content in the
      tissues mirrored one of the two nutrient loading trends. The leaf length,
      however, exhibited a significant negative correlation with the nutrient
      gradients. We propose that changes in the P content of T. hemprichii, followed by
      epiphytic algae biomass and N content of the tissues, may be the useful
      indicators of nutrient loading to coastal ecosystems. 

PMID- 24433999
TI  - Protected areas in the Atlantic facing the hazards of micro-plastic pollution:
      first diagnosis of three islands in the Canary Current.
AB  - Coastal zones and the biosphere as a whole show signs of cumulative degradation
      due to the use and disposal of plastics. To better understand the manifestation
      of plastic pollution in the Atlantic Ocean, we partnered with local communities
      to determine the concentrations of micro-plastics in 125 beaches on three islands
      in the Canary Current: Lanzarote, La Graciosa, and Fuerteventura. We found that,
      in spite of being located in highly-protected natural areas, all beaches in our
      study area are exceedingly vulnerable to micro-plastic pollution, with pollution
      levels reaching concentrations greater than 100 g of plastic in 1l of sediment.
      This paper contributes to ongoing efforts to develop solutions to plastic
      pollution by addressing the questions: (i) Where does this pollution come from?;
      (ii) How much plastic pollution is in the world's oceans and coastal zones?;
      (iii) What are the consequences for the biosphere?; and (iv) What are possible
      solutions?

PMID- 24434000
TI  - Predictable pollution: an assessment of weather balloons and associated impacts
      on the marine environment--an example for the Great Barrier Reef, Australia.
AB  - Efforts to curb pollution in the marine environment are covered by national and
      international legislation, yet weather balloons are released into the environment
      with no salvage agenda. Here, we assess impacts associated with weather balloons
      in the Great Barrier Reef World Heritage Area (GBRWHA). We use modeling to assess
      the probability of ocean endpoints for released weather balloons and predict
      pathways post-release. In addition, we use 21 months of data from beach cleanup
      events to validate our results and assess the abundance and frequency of weather
      balloon fragments in the GBRWHA. We found between 65% and 70% of balloons land in
      the ocean and ocean currents largely determine final endpoints. Beach cleanup
      data revealed 2460 weather balloon fragments were recovered from 24 sites within
      the GBRWHA. This is the first attempt to quantify this problem and these data
      will add support to a much-needed mitigation strategy for weather balloon waste.

PMID- 24434001
TI  - Environmental variabilities and the distribution of octocorals and black corals
      in Hong Kong.
AB  - A recent comprehensive survey covering 125 sites in Hong Kong waters recorded 29
      soft coral species in 14 genera, 38 species of gorgonians in 19 genera and six
      species of black corals in two genera. Environmental variabilities based on water
      quality data collected by Hong Kong Environmental Protection Department were
      analyzed using multivariate statistics to find variables that are significantly
      correlated with coral distribution patterns. Eleven water quality zones with
      similar environmental variabilities were recognized, which could further be
      classified into five groups, namely Inner Bay, Outer Bay, Eastern, Western and
      Southern waters. LINKTREE analysis provided an overall trend indicating the
      importance of salinity, sediment and nutrient loadings in affecting octocoral and
      black coral distribution from west to east of Hong Kong waters, and from inner to
      outer bays. Furthermore, water turbidity and wave exposure could also affect the
      coral distribution patterns from north, northeast to southern waters. 

PMID- 24434002
TI  - Usefulness of interictal spike source localization in temporal lobe epilepsy:
      electrocorticographic study.
AB  - The success of epilepsy surgery depends on delineation of the suspected
      epileptogenic zone. The gold standard to delineate it is to use the ictal onset
      zone from an electrocorticography (ECoG). Although interictal spikes are also
      associated with the epileptogenic zone, their clinical significance has been
      under-evaluated. The aim of this study was to evaluate the source localization of
      interictal spikes in terms of the association with epileptogenic zone in surgical
      temporal lobe epilepsy patients. The proposition is that the resection volume in
      patients with favorable outcomes includes the epileptogenic zone. The association
      with the epileptogenic zone was assessed as follows: (1) how many of the
      interictal spike sources are within the resection volume in patients with
      favorable outcomes and (2) how many of the interictal spike sources are outside
      the resection volume in patients with unfavorable outcomes. Thirty-eight temporal
      lobe epilepsy (TLE) patients who underwent both ECoG monitoring and epilepsy
      surgery were recruited and their 10min of ECoG recordings were analyzed. Six
      tumor-related TLE patients were excluded in the analysis. Of the remaining 32
      patients, 20 patients achieved favorable surgical outcomes (Engel I and II),
      while the surgical outcomes of 12 patients were unfavorable (Engel III and IV).
      In each patient, interictal spike sources were localized using sLORETA and co
      registered into a reconstructed brain model. The correspondence rate with the
      resection volume was estimated by counting the percentage of interictal spike
      sources in the resection volume. The correspondence rate in patients with
      favorable outcomes was 72.8+/-22.1, which was significantly higher than that
      (41.2+/-28.8) of the patients with unfavorable outcomes (p=0.002). Nine out of
      twelve patients (75%) with unfavorable outcomes had multiple interictal spike
      source clusters both interior and exterior to the resection volume, while 4 of
      the 20 patients with favorable outcomes (20%) had such multiple clusters
      (p=0.021). In conclusion, interictal spike sources are highly associated with the
      epileptogenic zone. ECoG interictal spike source localization could help in the
      delineation of the potential resection volume. 

PMID- 24434003
TI  - Effects of thiamine and thiamine pyrophosphate on epileptic episode model
      established with caffeine in rats.
AB  - This study examines the effect of thiamine (TH) and thiamine pyrophosphate (TPP)
      on epileptic episode model induced in rats with caffeine. Animals were divided
      into groups and given TH or TPP at doses of 10, 30 or 50mg/kg intraperitoneally.
      Subsequently, all animal groups were injected intraperitoneally with caffeine at
      a dose of 300mg/kg. Time of onset of epileptic episode was recorded, and the
      latent period was calculated in seconds. At the end of the experiment, tGSH and
      MDA levels and SOD and MPO enzyme activities in extracted brain tissues were
      measured. Latent period duration in rats in the control group was 134+/-3.2s,
      compared to 144+/-13.9, 147+/-14.5 and 169+/-15.1s, respectively, in the TH10,
      TH30 and TH50 groups and 184+/-8.54, 197+/-9.1, 225+/-8.37s, respectively, in the
      TPP10, TPP30 and TPP50 groups. Latent period duration was 236+/-6.7 in the
      diazepam group. Oxidant products were significantly lower in the TPP10, TPP30,
      TPP50 and diazepam groups compared to the control group (P<0.05), while SOD
      activity and tGSH levels were significantly higher (P<0.05). There was no
      significant difference between the TH10, TH30, TH50 groups and the control group
      in terms of oxidant and antioxidant levels (P>0.05). In conclusions, TPP,
      especially at a dose of 50mg/kg, significantly prolonged the latent period from
      administration of caffeine to time of episode and prevented oxidative damage. 

PMID- 24434005
TI  - Folding and stability studies on C-PE and its natural N-terminal truncant.
AB  - The conformational and functional state of biliproteins can be determined by
      optical properties of the covalently linked chromophores. alpha-Subunit of most
      of the phycoerythrin contains 164 residues. Recently determined crystal structure
      of the naturally truncated form of alpha-subunit of cyanobacterial phycoerythrin
      (Tr-alphaC-PE) lacks 31 N-terminal residues present in its full length form (FL
      alphaC-PE). This provides an opportunity to investigate the structure-function
      relationship between these two natural forms. We measured guanidinium chloride
      (GdmCl)-induced denaturation curves of FL-alphaC-PE and Tr-alphaC-PE proteins,
      followed by observing changes in absorbance at 565nm, fluorescence at 350 and
      573nm, and circular dichroism at 222nm. The denaturation curve of each protein
      was analyzed for DeltaGD(?), the value of Gibbs free energy change on
      denaturation (DeltaGD) in the absence of GdmCl. The main conclusions of the this
      study are: (i) GdmCl-induced denaturation (native state<->denatured state) of FL
      alphaC-PE and Tr-alphaC-PE is reversible and follows a two-state mechanism, (ii)
      FL-alphaC-PE is 1.4kcalmol(-1) more stable than Tr-alphaC-PE, (iii) truncation of
      31-residue long fragment that contains two alpha-helices, does not alter the 3-D
      structure of the remaining protein polypeptide chain, protein-chromophore
      interaction, and (iv) amino acid sequence of Tr-alphaC-PE determines the
      functional structure of the phycoerythrin. 

PMID- 24434004
TI  - Conformational changes involving ammonia tunnel formation and allosteric control
      in GMP synthetase.
AB  - GMP synthetase is the glutamine amidotransferase that catalyzes the final step in
      the guanylate branch of de novo purine biosynthesis. Conformational changes are
      required to efficiently couple distal active sites in the protein; however, the
      nature of these changes has remained elusive. Structural information derived from
      both limited proteolysis and sedimentation velocity experiments support the
      hypothesis of nucleotide-induced loop- and domain-closure in the protein. These
      results were combined with information from sequence conservation and precedents
      from other glutamine amidotransferases to develop the first structural model of
      GMPS in a closed, active state. In analyzing this Catalytic model, an interdomain
      salt bridge was identified residing in the same location as seen in other triad
      glutamine amidotransferases. Using mutagenesis and kinetic analysis, the salt
      bridge between H186 and E383 was shown to function as a connection between the
      two active sites. Mutations at these residues uncoupled the two half-reactions of
      the enzyme. The chemical events of nucleotide binding initiate a series of
      conformational changes that culminate in the establishment of a tunnel for
      ammonia as well as an activated glutaminase catalytic site. The results of this
      study provide a clearer understanding of the allostery of GMPS, where, for the
      first time, key substrate binding and interdomain contacts are modeled and
      analyzed. 

PMID- 24434006
TI  - NMR studies of interactions between Bax and BH3 domain-containing peptides in the
      absence and presence of CHAPS.
AB  - Activation and oligomerisation of Bax, a key pro-apoptotic Bcl-2 family protein,
      are key steps in the mitochondrial pathway to apoptosis. The signals for
      apoptosis are conveyed by the distantly related BH3-only proteins, which use
      their short BH3 domain, an amphipathic alpha-helix, to interact with other Bcl-2
      family members. Here we report an NMR study of interactions between BaxDeltaC and
      BH3 domain-containing peptides in the absence and presence of CHAPS, a
      zwitterionic detergent. We find for the first time that CHAPS interacts weakly
      with BaxDeltaC (fast exchange on the NMR chemical shift timescale), at
      concentrations below micelle formation and with an estimated Kd in the tens of
      mM. Direct and relatively strong-interactions (slow exchange on the NMR chemical
      shift timescale) were also observed for BaxDeltaC with BaxBH3 (estimated Kd of
      circa 150MUM) or BimBH3 in the absence of CHAPS. The interaction with either
      peptide alone induced widespread chemical shift perturbations to BaxDeltaC in
      solution which implies that BaxDeltaC might have undergone significant
      conformation change upon binding the BH3 peptide. However, BaxDeltaC remained
      monomeric upon binding either CHAPS or a BH3 peptide alone, but the presence of
      both provoked it to form a dimer. 

PMID- 24434007
TI  - [Ketamine's antidepressant effect: focus on ketamine mechanisms of action].
AB  - BACKGROUND: In recent years, discovery of ketamine's fast and powerful
      antidepressant effects for treatment-resistant depression (TRD) has led to
      rethinking of the pathophysiology of depression. Numerous studies in humans and
      animals have focused on mechanisms of action underlying this effect, producing a
      number of explanatory pathways. METHOD: The aim of this article is to summarize
      the various hypotheses underlying rapid antidepressant action of ketamine and
      therefore to better understand the mechanisms underlying depression and
      antidepressant action. RESULTS: Ketamine unique antidepressant properties have
      led to many studies on its neurobiological grounds. Intracellular signaling
      pathways such as mTOR, GSK3 or eEF2 seem to play a key role and are associated
      with an increased synaptic plasticity. Other hypotheses are discussed such as
      ketamine effects on neuro-inflammation, the role of anterior cingulate cortex in
      brain changes induced by ketamine, and the potential benefits of analgesic
      properties of ketamine in depressive disorders. CONCLUSION: Our review highlights
      the potential role of the glutamatergic system in the pathophysiology and
      treatment of mood disorders. Understanding which pathways underlie the fast
      antidepressant effect of ketamine paves the way for the development of new
      antidepressants.

PMID- 24434008
TI  - [Ketamine's antidepressant effect: literature review on clinical use].
AB  - BACKGROUND: Depressive disorders have a major impact on public health. They are
      prevalent and disabling, with high economic burden for society. Antidepressants
      have a delayed action and at least one third of patients do not achieve adequate
      response. The recent discovery of ketamine's unique antidepressant properties,
      with rapid onset of response and high rate of responders opens new perspectives
      for treatment-resistant depression (TRD). METHOD: The aim of this article is to
      summarize preclinical trials and clinical trials demonstrating ketamine
      antidepressant properties and to review the different modalities of use. RESULTS:
      Most clinical studies used ketamine with a single subanesthetic intravenous
      administration in patients with treatment-resistant depression, demonstrating a
      rapid but transient antidepressant response with high response rates. To prevent
      relapse and maintain the initial benefits, few studies have shown the interest of
      serial infusions of ketamine, while others combined ketamine and
      electroconvulsive therapy using the former as an anesthetic. So far, relay
      treatments with glutamatergic agents such as riluzole are disappointing. Although
      most studies were conducted in patients with TRD in recurrent depression or
      bipolar disorder, efficacy in acutely suicidal patients is promising. CONCLUSION:
      Our review highlights the increasing interest in the use of ketamine in the
      treatment of treatment-resistant depression. Although a widespread use of
      ketamine as an antidepressant in routine clinical settings seems limited by
      psychotomimetic effects and the lack of strategy to maintain initial benefits,
      ketamine or related drugs might be used to target specific conditions, such as
      bipolar depression or high suicide risk.

PMID- 24434009
TI  - Another year of microbial pathogens and the host immune response.

PMID- 24434010
TI  - HDAC6 is overexpressed in cystic cholangiocytes and its inhibition reduces
      cystogenesis.
AB  - Polycystic liver disease (PLD) is a member of the cholangiopathies, a group of
      liver diseases in which cholangiocytes, the epithelia lining of the biliary tree,
      are the target cells. PLDs are caused by mutations in genes involved in
      intracellular signaling pathways, cell cycle regulation, and ciliogenesis, among
      others. We previously showed that cystic cholangiocytes have abnormal cell cycle
      profiles and malfunctioning cilia. Because histone deacetylase 6 (HDAC6) plays an
      important role in both cell cycle regulation and ciliary disassembly, we examined
      the role of HDAC6 in hepatic cystogenesis. HDAC6 protein was increased sixfold in
      cystic liver tissue and in cultured cholangiocytes isolated from both PCK rats
      (an animal model of PLD) and humans with PLD. Furthermore, pharmacological
      inhibition of HDAC6 by Tubastatin-A, Tubacin, and ACY-1215 decreased
      proliferation of cystic cholangiocytes in a dose- and time-dependent manner, and
      inhibited cyst growth in three-dimensional cultures. Importantly, ACY-1215
      administered to PCK rats diminished liver cyst development and fibrosis. In
      summary, we show that HDAC6 is overexpressed in cystic cholangiocytes both in
      vitro and in vivo, and its pharmacological inhibition reduces cholangiocyte
      proliferation and cyst growth. These data suggest that HDAC6 may represent a
      potential novel therapeutic target for cases of PLD. 

PMID- 24434011
TI  - Complex cellular composition of solitary fibrous tumor of the prostate.
AB  - Solitary fibrous tumors (SFTs) of the prostate are a rare type of spindle cell
      neoplasm that can demonstrate either a benign or malignant phenotype. SFTs
      represent a clinical challenge along with other spindle cell lesions of the
      prostate in terms of both diagnosis and treatment. The present study shows, for
      the first time, that SFTs of the prostate and other organs can comprise a mixed
      population of fibroblast, myofibroblast, and smooth muscle cell types. The highly
      proliferative component demonstrated a fibroblastic phenotype that readily
      underwent myofibroblast differentiation on exposure to profibrotic stimuli.
      Consistent with other recent studies, the prostatic SFTs demonstrated NAB2-STAT6
      gene fusions that were also present in the fibroblast, myofibroblast, and smooth
      muscle cell types of the SFT. The results of these studies suggest that benign
      and malignant prostatic tumors of mesenchymal origin may be distinguished at the
      molecular and cellular levels, and that delineation of such defining
      characteristics may help elucidate the etiology and prognosis of such tumors. 

PMID- 24434013
TI  - The production of radionuclides for nuclear medicine from a compact, low-energy
      accelerator system.
AB  - INTRODUCTION: The field of nuclear medicine is reliant on radionuclides for
      medical imaging procedures and radioimmunotherapy (RIT). The recent shut-downs of
      key radionuclide producers have highlighted the fragility of the current
      radionuclide supply network, however. To ensure that nuclear medicine can
      continue to grow, adding new diagnostic and therapy options to healthcare, novel
      and reliable production methods are required. Siemens are developing a low
      energy, high-current - up to 10 MeV and 1 mA respectively - accelerator. The
      capability of this low-cost, compact system for radionuclide production, for use
      in nuclear medicine procedures, has been considered. METHODOLOGY: The production
      of three medically important radionuclides - (89)Zr, (64)Cu, and (103)Pd - has
      been considered, via the (89)Y(p,n), (64)Ni(p,n) and (103)Rh(p,n) reactions,
      respectively. Theoretical cross-sections were generated using TALYS and compared
      to experimental data available from EXFOR. Stopping power values generated by
      SRIM have been used, with the TALYS-generated excitation functions, to calculate
      potential yields and isotopic purity in different irradiation regimes. RESULTS:
      The TALYS excitation functions were found to have a good agreement with the
      experimental data available from the EXFOR database. It was found that both
      (89)Zr and (64)Cu could be produced with high isotopic purity (over 99%), with
      activity yields suitable for medical diagnostics and therapy, at a proton energy
      of 10MeV. At 10MeV, the irradiation of (103)Rh produced appreciable quantities of
      (102)Pd, reducing the isotopic purity. A reduction in beam energy to 9.5MeV
      increased the radioisotopic purity to 99% with only a small reduction in activity
      yield. CONCLUSION: This work demonstrates that the low-energy, compact
      accelerator system under development by Siemens would be capable of providing
      sufficient quantities of (89)Zr, (64)Cu, and (103)Pd for use in medical
      diagnostics and therapy. It is suggested that the system could be used to produce
      many other isotopes currently useful to nuclear medicine.

PMID- 24434012
TI  - The senescence-associated secretory phenotype promotes benign prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in
      the transition zone of the prostate, which leads to obstruction of urine outflow
      and considerable morbidity in a majority of older men. Senescent cells accumulate
      in human tissues, including the prostate, with increasing age. Expression of
      proinflammatory cytokines is increased in these senescent cells, a manifestation
      of the senescence-associated secretory phenotype. Multiplex analysis revealed
      that multiple cytokines are increased in BPH, including GM-CSF, IL-1alpha, and IL
      4, and that these are also increased in senescent prostatic epithelial cells in
      vitro. Tissue levels of these cytokines were correlated with a marker of
      senescence (cathepsin D), which was also strongly correlated with prostate
      weight. IHC analysis revealed the multifocal epithelial expression of cathepsin D
      and coexpression with IL-1alpha in BPH tissues. In tissue recombination studies
      in nude mice with immortalized prostatic epithelial cells expressing IL-1alpha
      and prostatic stromal cells, both epithelial and stromal cells exhibited
      increased growth. Expression of IL-1alpha in prostatic epithelial cells in a
      transgenic mouse model resulted in increased prostate size and bladder
      obstruction. In summary, both correlative and functional evidence support the
      hypothesis that the senescence-associated secretory phenotype can promote the
      development of BPH, which is the single most common age-related pathology in
      older men. 

PMID- 24434014
TI  - Transcriptional response of kidney tissue after 177Lu-octreotate administration
      in mice.
AB  - INTRODUCTION: The kidneys are one of the main dose limiting organs in (177)Lu
      octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation
      damage would be of great importance in this type of therapy. The purpose of this
      study was to investigate the absorbed dose dependency on early transcriptional
      changes in the kidneys from (177)Lu-octreotate exposure. METHODS: Female Balb/c
      nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq (177)Lu-octreotate.
      The animals were killed 24 h after injection followed by excision of the kidneys.
      The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was
      extracted from separated renal tissue samples, and applied to Illumina MouseRef-8
      Whole-Genome Expression Beadchips to identify regulated transcripts after
      irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data
      processing and to determine affected biological processes. RESULTS: Distinct
      transcriptional responses were observed following (177)Lu-octreotate
      administration. A higher number of differentially expressed transcripts were
      observed in the kidney medulla (480) compared to cortex (281). In addition, 39
      transcripts were regulated at all absorbed dose levels in the medulla, compared
      to 32 in the cortex. Three biological processes in the cortex and five in the
      medulla were also shared by all absorbed dose levels. Strong association to
      metabolism was found among the affected processes in both tissues. Furthermore,
      an association with cellular and developmental processes was prominent in kidney
      medulla, while transport and immune response were prominent in kidney cortex.
      CONCLUSION: Specific biological and dose-dependent responses were observed in
      both tissues. The number of affected transcripts and biological processes
      revealed distinct response differences between the absorbed doses delivered to
      the tissues.

PMID- 24434015
TI  - [Cardiovascular involvement in Behcet's disease].
AB  - Vascular involvement is a common complication of Behcet's disease (BD) and
      affects up to 40% of BD patients. These complications worsen the prognosis of BD.
      The concept of vasculo-Behcet has been adopted for cases in which vascular
      complications dominate the clinical features. Vascular manifestations affect
      particularly young men, during the first years following onset of the disease.
      Venous complications are the most frequent vascular complications, affecting 14
      to 40% of BD patients. Superficial and deep lower limb thrombosis is the most
      frequent venous complications but one third of venous thrombosis concern large
      vessels (such as cerebral venous thrombosis, pulmonary embolism, and inferior or
      superior vena cava, etc.). Budd-Chiari syndrome is the worst prognostic factor
      increasing mortality by 9 times. Arterial complications (2 to 17% of BD patients)
      include aneurysms and occlusions/stenosis. Main locations of arterial lesions are
      aortic (abdominal and thoracic), femoral, pulmonary and iliac arteries. Aneurysms
      are the most severe arterial complications, particularly pulmonary aneurysms
      associated with a high risk of massive bleeding. Cardiac complications (up to 6%
      of BD patients) include pericarditis, endocardial lesions (aortic regurgitation
      and less often mitral insufficiency), myocardial lesions (myocardial infarction,
      myocarditis and endomyocardial fibrosis) and intracardiac thrombosis (right
      ventricle and atrium). Coronary lesions complicated to myocardial infarction are
      the most severe cardiac complications. Treatment is based on corticosteroids and
      immunosuppressive drugs. The use of anticoagulation in venous thrombosis is still
      controversial. 

PMID- 24434016
TI  - Early adolescent patterns of alcohol, cigarettes, and marijuana polysubstance use
      and young adult substance use outcomes in a nationally representative sample.
AB  - BACKGROUND: Alcohol, tobacco and marijuana are the most commonly used drugs by
      adolescents in the U.S. However, little is known about the patterning of early
      adolescent substance use, and its implications for problematic involvement with
      substances in young adulthood. We examined patterns of substance use prior to age
      16, and their associations with young adult substance use behaviors and substance
      use disorders in a nationally representative sample of U.S. adolescents. METHOD:
      Using data from Wave 4 of the Add Health Survey (n=4245), we estimated the
      prevalence of various patterns of early adolescent use of alcohol, cigarettes,
      and marijuana use individually and in combination. Then we examined the effects
      of patterns of early use of these substances on subsequent young adult substance
      use behaviors and DSM-IV substance use disorders. RESULTS: While 34.4% of
      individuals reported no substance use prior to age 16, 34.1% reported either
      early use of both alcohol and marijuana or alcohol, marijuana and cigarettes,
      indicating the relatively high prevalence of this type of polysubstance use
      behavior among U.S. adolescents. Early adolescent use of all three substances was
      most strongly associated with a spectrum of young adult substance use problems,
      as well as DSM-IV substance use disorder diagnoses. CONCLUSIONS: This research
      confirms the elevated prevalence and importance of polysubstance use behavior
      among adolescents prior to age 16, and puts early onset of alcohol, marijuana and
      cigarette use into the context of use patterns rather than single drug exposures.

PMID- 24434017
TI  - MDWiZ: a platform for the automated translation of molecular dynamics
      simulations.
AB  - A variety of popular molecular dynamics (MD) simulation packages were
      independently developed in the last decades to reach diverse scientific goals.
      However, such non-coordinated development of software, force fields, and analysis
      tools for molecular simulations gave rise to an array of software formats and
      arbitrary conventions for routine preparation and analysis of simulation input
      and output data. Different formats and/or parameter definitions are used at each
      stage of the modeling process despite largely contain redundant information
      between alternative software tools. Such Babel of languages that cannot be easily
      and univocally translated one into another poses one of the major technical
      obstacles to the preparation, translation, and comparison of molecular simulation
      data that users face on a daily basis. Here, we present the MDWiZ platform, a
      freely accessed online portal designed to aid the fast and reliable preparation
      and conversion of file formats that allows researchers to reproduce or generate
      data from MD simulations using different setups, including force fields and
      models with different underlying potential forms. The general structure of MDWiZ
      is presented, the features of version 1.0 are detailed, and an extensive
      validation based on GROMACS to LAMMPS conversion is presented. We believe that
      MDWiZ will be largely useful to the molecular dynamics community. Such fast
      format and force field exchange for a given system allows tailoring the chosen
      system to a given computer platform and/or taking advantage of a specific
      capabilities offered by different software engines. 

PMID- 24434018
TI  - Models for H3 receptor antagonist activity of sulfonylurea derivatives.
AB  - The histamine H3 receptor has been perceived as an auspicious target for the
      treatment of various central and peripheral nervous system diseases. In present
      study, a wide variety of 60 2D and 3D molecular descriptors (MDs) were
      successfully utilized for the development of models for the prediction of
      antagonist activity of sulfonylurea derivatives for histamine H3 receptors.
      Models were developed through decision tree (DT), random forest (RF) and moving
      average analysis (MAA). Dragon software version 6.0.28 was employed for
      calculation of values of diverse MDs of each analogue involved in the data set.
      The DT classified and correctly predicted the input data with an impressive non
      error rate of 94% in the training set and 82.5% during cross validation. RF
      correctly classified the analogues into active and inactive with a non-error rate
      of 79.3%. The MAA based models predicted the antagonist histamine H3 receptor
      activity with non-error rate up to 90%. Active ranges of the proposed MAA based
      models not only exhibited high potency but also showed improved safety as
      indicated by relatively high values of selectivity index. The statistical
      significance of the models was assessed through sensitivity, specificity, non
      error rate, Matthew's correlation coefficient and intercorrelation analysis.
      Proposed models offer vast potential for providing lead structures for
      development of potent but safe H3 receptor antagonist sulfonylurea derivatives.

PMID- 24434020
TI  - Urinary phytoestrogens and depression in perimenopausal US women: NHANES 2005
      2008.
AB  - BACKGROUND: Fluctuating hormonal levels observed during the menopausal transition
      may increase vulnerability to depression in susceptible women. Thus, it is of
      interest to examine the effect of natural estrogens such as phytoestrogens on the
      risk of depression in perimenopausal women. METHODS: Our analysis included 193
      perimenopausal women of the National Health and Nutrition Survey (NHANES) 2005
      2008 aged 45-55 years. Urinary concentrations of phytoestrogens (isoflavones and
      lignans) were measured by HPLC-APPI-MS/MS. Depression was assessed using the
      Patient Health Questionnaire-9 (PHQ-9). Logistic regression models examined the
      association of phytoestrogens concentrations (creatinine-standardized and log
      transformed) with depression (yes/no). RESULTS: Unadjusted odds ratios (OR) of
      the associations between urinary phytoestrogen concentrations and perimenopausal
      depression were below 1; however, only lignans were significantly inversely
      associated with depression. The latter findings were not attenuated in
      multivariate analysis including age, race, body mass index, poverty income ratio,
      smoking, alcohol consumption, cancer, diabetes, and cardiovascular disease
      (lignans: OR=0.66; 95% confidence intervals (CI) 0.50-0.87, enterodiol: OR=0.63;
      95% CI 0.51-0.78, enterolactone: OR=0.75; 95% CI 0.60-0.93). LIMITATIONS: Our
      cross-sectional study design does not allow for causal inferences. Because
      information to precisely assess perimenopausal symptoms was missing, we defined
      perimenopause based on women's age. CONCLUSIONS: Lower lignans but not
      isoflavones concentrations were statistically significantly associated with an
      increased risk of depression in perimenopausal women. Because of medical risks
      associated with the use of hormone therapy, further investigation on the effect
      of lignans on the risk of depression in perimenopausal women is warranted.

PMID- 24434019
TI  - Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of
      the Wnt/beta-catenin signaling pathway and epithelial-mesenchymal transition.
AB  - The aberrant activation of Wnt/beta-catenin signaling plays an important role in
      the carcinogenesis and progression of hepatocellular carcinoma (HCC). Therefore,
      the Wnt/beta-catenin signaling molecules are attractive candidates for the
      development of targeted therapies for this disease. The present study showed that
      destruxin B (DB) inhibits the proliferation and induces the apoptosis of HCC
      cells by decreasing the protein expression of anti-apoptotic Bcl-2 and Bcl-xL and
      increasing the expression of the proapoptotic protein Bax. More importantly, DB
      also attenuates Wnt-signaling in HCC cells by downregulating beta-catenin, Tcf4,
      and beta-catenin/Tcf4 transcriptional activity, which results in the decreased
      expression of beta-catenin target genes, such as cyclin D1, c-myc, and survivin.
      Furthermore, DB affects the migratory and invasive abilities of Sk-Hep1 cells
      through the suppression of markers of the epithelial-mesenchymal transition
      (EMT). A synergistic anti-proliferative and migratory effect was achieved using
      the combination of DB and sorafenib in Sk-Hep1 cells. In conclusion, DB acts as a
      novel Wnt/beta-catenin inhibitor and reduces the aggressiveness and invasive
      potential of HCC by altering the cells' EMT status and mobility. DB in
      combination with sorafenib may be considered for future clinical use for the
      management of metastatic HCC. 

PMID- 24434021
TI  - Adrenal collision tumors and their mimics: multimodality imaging findings.
AB  - Adrenal collision tumors (ACTs) refer to coexistence of two adjacent, but
      histologically distinct neoplasms involving the adrenal gland without histologic
      admixture at interface. ACTs include adenoma with myelolipoma, adenoma with
      metastases, hemangioma with adenoma, and adrenocortical carcinoma with
      myelolipoma. In addition, hemorrhage into a pre-existing adrenal mass can mimic
      an ACT, and it is important to differentiate these two pathologies. Accurate
      characterization of ACTs is difficult, but critical, for correct staging of
      patients with malignancies and to guide percutaneous biopsy. Magnetic resonance
      imaging (MRI) and multidetector computed tomography imaging techniques may depict
      different tumor components separately; however, biopsy may be required in
      selected patients for confirmation. [(18)F]Fluorodeoxyglucose-positron emission
      tomography (PET) shows increased uptake in the malignant component of ACTs, and
      guides percutaneous biopsy. Even in patients requiring percutaneous biopsy for a
      definite diagnosis, imaging findings can help in guiding the appropriate
      component to be biopsied. Knowledge of imaging findings of different ACTs and
      their mimics on MRI, computed tomography, and PET help in optimal patient
      management. 

PMID- 24434022
TI  - Age-related changes in neural recruitment for cognitive control.
AB  - The dual mechanisms of control (DMC; Braver, Gray, & Burgess, 2007) framework
      postulates a distinction between proactive and reactive modes of cognitive
      control. Event-related brain potentials (ERPs) were used to examine age
      differences in the neural correlates of proactive and reactive control for task
      switching. Whereas proactive control is associated with brain activity for
      anticipatory task preparation, reactive control is accompanied by reduced
      preparatory activity, but increased activation during task execution. Switching
      between tasks was based on feedback-based transition cueing which places
      particularly high demands on mechanisms for cognitive control. Older adults
      maintained good performance accuracy at the expense of slower response times. No
      age-related increase in behavioral switching costs was observed. The cue-locked
      ERP (P3a) data revealed an age-related decrease in neural activity related to the
      processing of switch cues. In the target-locked ERPs, there was an increased
      frontal focus of the P3b in older adults. These ERP data indicate an age-related
      neural under-recruitment for proactive cognitive control and an age-related
      neural over-recruitment for reactive cognitive control. They are consistent with
      the idea that older adults may not fully implement task settings before target
      onset, after which they need to catch up on the omitted preparatory task
      settings. 

PMID- 24434023
TI  - The HIF-2alpha dependent induction of PAP and adenosine synthesis regulates
      glioblastoma stem cell function through the A2B adenosine receptor.
AB  - Glioblastomas are lethal tumors characterized by malignant proliferation and
      recurrence promoted partly by glioblastoma stem cells (GSCs). GSCs are known to
      be regulated by hypoxia, but the mechanisms involved in this regulation are not
      fully understood. We now demonstrate that hypoxia-inducible factor HIF2alpha and
      prostatic acid phosphatase (PAP) are preferentially expressed in hypoxic GSCs in
      comparison with non-stem tumor cells and normal neural stem cells and that PAP is
      regulated by HIF2alpha. Targeting PAP in hypoxic GSCs inhibits self-renewal and
      proliferation in vitro and attenuates tumor initiation potential of GSCs in vivo.
      Using specific adenosine receptor antagonists, we further find that the pro
      proliferative role of PAP is stemmed from stimulated A2B adenosine receptors.
      Moreover, selective blockage of A2B receptor or knockdown of PAP or A2B on
      hypoxic GSCs results in significant reduction of phosphorylation of Akt and Erk
      1/2. Our results demonstrate that PAP may play a pro-proliferative role in
      hypoxic GSCs with a HIF2alpha-induction pattern, which may be ascribed to
      stimulated A2B receptors and activated Akt and Erk-1/2 pathways. Therefore, we
      propose that these identified molecular regulators of GSCs in the hypoxic niche
      might represent promising targets for antiglioblastoma therapies. 

PMID- 24434024
TI  - Task effects reveal cognitive flexibility responding to frequency and
      predictability: evidence from eye movements in reading and proofreading.
AB  - It is well-known that word frequency and predictability affect processing time.
      These effects change magnitude across tasks, but studies testing this use tasks
      with different response types (e.g., lexical decision, naming, and fixation time
      during reading; Schilling, Rayner, & Chumbley, 1998), preventing direct
      comparison. Recently, Kaakinen and Hyona (2010) overcame this problem, comparing
      fixation times in reading for comprehension and proofreading, showing that the
      frequency effect was larger in proofreading than in reading. This result could be
      explained by readers exhibiting substantial cognitive flexibility, and
      qualitatively changing how they process words in the proofreading task in a way
      that magnifies effects of word frequency. Alternatively, readers may not change
      word processing so dramatically, and instead may perform more careful
      identification generally, increasing the magnitude of many word processing
      effects (e.g., both frequency and predictability). We tested these possibilities
      with two experiments: subjects read for comprehension and then proofread for
      spelling errors (letter transpositions) that produce nonwords (e.g., trcak for
      track as in Kaakinen & Hyona) or that produce real but unintended words (e.g.,
      trial for trail) to compare how the task changes these effects. Replicating
      Kaakinen and Hyona, frequency effects increased during proofreading. However,
      predictability effects only increased when integration with the sentence context
      was necessary to detect errors (i.e., when spelling errors produced words that
      were inappropriate in the sentence; trial for trail). The results suggest that
      readers adopt sophisticated word processing strategies to accommodate task
      demands. 

PMID- 24434025
TI  - Development of a medical academic degree system in China.
AB  - CONTEXT: The Chinese government launched a comprehensive healthcare reform to
      tackle challenges to health equities. Medical education will become the key for
      successful healthcare reform. PURPOSE: We describe the current status of the
      Chinese medical degree system and its evolution over the last 80 years. CONTENT:
      Progress has been uneven, historically punctuated most dramatically by the
      Cultural Revolution. There is a great regional disparity. Doctors with limited
      tertiary education may be licensed to practice, whereas medical graduates with
      advanced doctorates may have limited clinical skills. There are undefined
      relationships between competing tertiary training streams, the academic
      professional degree, and the clinical residency training programme (RTP). The
      perceived quality of training in both streams varies widely across China. As the
      degrees of master or doctor of academic medicine is seen as instrumental in
      career advancement, including employability in urban hospitals, attainment of
      this degree is sought after, yet is often unrelated to a role in health care, or
      is seen as superior to clinical experience. Meanwhile, the practical experience
      gained in some prestigious academic institutions is deprecated by the RTP and
      must be repeated before accreditation for clinical practice. This complexity is
      confusing both for students seeking the most appropriate training, and also for
      clinics, hospitals and universities seeking to recruit the most appropriate
      applicants. CONCLUSION: The future education reforms might include: 1) a domestic
      system of 'credits' that gives weight to quality clinical experience vs. academic
      publications in career advancement, enhanced harmonisation between the competing
      streams of the professional degree and the RTP, and promotion of mobility of
      staff between areas of excellence and areas of need; 2) International - a mutual
      professional and academic recognition between China and other countries by
      reference to the Bologna Accord, setting up a system of easily comparable and
      well-understood medical degrees.

PMID- 24434026
TI  - Student performance and grading changes in a systems-based curriculum.
AB  - INTRODUCTION: Changing from a conventional discipline-based, basic science
      medical school curriculum to an integrated systems-based curriculum, which was
      graded on overall performance not by discipline, was associated with a highly
      significant improvement in an externally administered comprehensive exam at the
      end of the 2-year basic science program. The reason for the improvement was
      unclear, but we hypothesized that it was partly due to a change in student study
      strategy. Anecdotal evidence suggested that students had changed their study
      habits to spend less time on previously harder-to-pass courses and more time on
      courses with previously lower failure rates. If this were so, performance in
      previously harder disciplines might have deteriorated, while performance in
      previously easier disciplines could have improved. METHODS: We examined relative
      performance in the four discipline-based courses of Systemic Pathology,
      Microbiology, Pharmacology, and Introductory Clinical Medicine (ICM) in the
      fourth (and last) semester of the curriculum. We compared failure rates in these
      four courses for the three cohorts before the change with the three cohorts
      after. RESULTS: Pharmacology and Microbiology which had failure rates over twice
      as high as Systemic Pathology and ICM in the conventional program before the
      curriculum change showed a deterioration in performance after the change with an
      approximately threefold rise in internal failure rate. In contrast, Systemic
      Pathology showed a dramatic improvement with a more than threefold drop in the
      failure rate, while the ICM clinical skills course, which was largely assessed by
      a practical exam in all 6 cohorts, showed no change. CONCLUSION: The improvement
      in student performance in an external assessment may be due, at least partly, to
      a change in the school's internal grading policy which led to a more appropriate
      balancing of student study strategies. Future studies on the effect of curriculum
      change should include an assessment of the impact on student study strategies.

PMID- 24434027
TI  - Turning the corner with the flash-lag illusion.
AB  - Previous attempts to measure localization bias around a right-angle turn (L
      trajectory) have found either no spatial bias off the trajectory (Whitney,
      Cavanagh, & Murakami, 2000) or a bias, in different experiments, both 'inside'
      and 'outside' the trajectory (Nieman, Sheth, & Shimojo, 2010). However, Eagleman
      and Sejnowski (2007) presented data showing that the perceived location of a
      brief feature on two moving stimuli could be predicted from the vector sum of
      their directions after the feature appeared. Such a vector sum with an L
      trajectory could predict that the perceived position before the turn should be
      biased 'sideways' off the trajectory, in the direction of the final motion. With
      stimuli that particularly facilitated accurate vernier judgments, and measuring
      bias via the flash-lag illusion, this is indeed what we observed. Our data thus
      favour Eagleman and Sejnowski's (2007) supposition. Further, the bias occurred
      before the change in direction, rather than after it, supporting the contention
      that it is motion after a point being sampled that affects its perception
      (Bachmann et al., 2003; Eagleman & Sejnowski, 2007; Krekelberg & Lappe, 2000;
      Nieman, Sheth, & Shimojo, 2010). 

PMID- 24434028
TI  - Characterization of wave phenomena in the relaxation of flash-induced chlorophyll
      fluorescence yield in cyanobacteria.
AB  - Fluorescence yield relaxation following a light pulse was studied in various
      cyanobacteria under aerobic and microaerobic conditions. In Synechocystis PCC
      6803 fluorescence yield decays in a monotonous fashion under aerobic conditions.
      However, under microaerobic conditions the decay exhibits a wave feature showing
      a dip at 30-50 ms after the flash followed by a transient rise, reaching maximum
      at ~1s, before decaying back to the initial level. The wave phenomenon can also
      be observed under aerobic conditions in cells preilluminated with continuous
      light. Illumination preconditions cells for the wave phenomenon transiently: for
      few seconds in Synechocystis PCC 6803, but up to one hour in Thermosynechocystis
      elongatus BP-1. The wave is eliminated by inhibition of plastoquinone binding
      either to the QB site of Photosystem-II or the Qo site of cytochrome b6f complex
      by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea or 2,5-dibromo-3-methyl-6-isopropyl
      p-benzoquinone, respectively. The wave is also absent in mutants, which lack
      either Photosystem-I or the NAD(P)H-quinone oxidoreductase (NDH-1) complex.
      Monitoring the redox state of the plastoquinone pool revealed that the dip of the
      fluorescence wave corresponds to transient oxidation, whereas the following rise
      to re-reduction of the plastoquinone pool. It is concluded that the unusual wave
      feature of fluorescence yield relaxation reflects transient oxidation of highly
      reduced plastoquinone pool by Photosystem-I followed by its re-reduction from
      stromal components via the NDH-1 complex, which is transmitted back to the
      fluorescence yield modulator primary quinone electron acceptor via charge
      equilibria. Potential applications of the wave phenomenon in studying
      photosynthetic and respiratory electron transport are discussed. This article is
      part of a special issue entitled: photosynthesis research for sustainability:
      keys to produce clean energy.

PMID- 24434029
TI  - Update on the pathogenesis of bullous pemphigoid: an autoantibody-mediated
      blistering disease targeting collagen XVII.
AB  - Bullous pemphigoid (BP) is a common autoimmune blistering skin disorder that
      tends to affect the elderly. Autoantibodies (autoAbs) from BP patients react with
      two hemidesmosomal components: transmembrane collagen XVII (BP180 or BPAG2) and
      plakin family protein BP230 (BPAG1). Of these, collagen XVII (COL17) is thought
      to be a major autoantigen. The binding of autoAbs to COL17 following the
      activation of complements and inflammatory pathways eventually leads to the
      degradation of COL17, and this has been regarded as the main pathogenesis of BP.
      However, recent investigations have suggested other pathways, including a
      complement-independent pathway and a pathway involving IgE-autoAbs. BP-autoAbs
      can directly deplete COL17, leading to fragility of the dermal-epidermal
      junction. In addition, IgE-autoAbs to COL17 may be involved in the formation of
      itchy urticarial erythema associated with eosinophilic infiltration. This article
      summarizes the update on pathogenesis of BP, with a special focus on blister
      formation by autoAbs to COL17. 

PMID- 24434030
TI  - Rapid decline in nuclear costitutive photomorphogenesis1 abundance anticipates
      the stabilization of its target elongated hypocotyl5 in the light.

PMID- 24434031
TI  - Rule-based deduplication of article records from bibliographic databases.
AB  - We recently designed and deployed a metasearch engine, Metta, that sends queries
      and retrieves search results from five leading biomedical databases: PubMed,
      EMBASE, CINAHL, PsycINFO and the Cochrane Central Register of Controlled Trials.
      Because many articles are indexed in more than one of these databases, it is
      desirable to deduplicate the retrieved article records. This is not a trivial
      problem because data fields contain a lot of missing and erroneous entries, and
      because certain types of information are recorded differently (and
      inconsistently) in the different databases. The present report describes our rule
      based method for deduplicating article records across databases and includes an
      open-source script module that can be deployed freely. Metta was designed to
      satisfy the particular needs of people who are writing systematic reviews in
      evidence-based medicine. These users want the highest possible recall in
      retrieval, so it is important to err on the side of not deduplicating any records
      that refer to distinct articles, and it is important to perform deduplication
      online in real time. Our deduplication module is designed with these constraints
      in mind. Articles that share the same publication year are compared sequentially
      on parameters including PubMed ID number, digital object identifier, journal
      name, article title and author list, using text approximation techniques. In a
      review of Metta searches carried out by public users, we found that the
      deduplication module was more effective at identifying duplicates than EndNote
      without making any erroneous assignments. 

PMID- 24434032
TI  - DBM-DB: the diamondback moth genome database.
AB  - The diamondback moth Genome Database (DBM-DB) is a central online repository for
      storing and integrating genomic data of diamondback moth (DBM), Plutella
      xylostella (L.). It provides comprehensive search tools and downloadable datasets
      for scientists to study comparative genomics, biological interpretation and gene
      annotation of this insect pest. DBM-DB contains assembled transcriptome datasets
      from multiple DBM strains and developmental stages, and the annotated genome of
      P. xylostella (version 2). We have also integrated publically available ESTs from
      NCBI and a putative gene set from a second DBM genome (KONAGbase) to enable users
      to compare different gene models. DBM-DB was developed with the capacity to
      incorporate future data resources, and will serve as a long-term and open-access
      database that can be conveniently used for research on the biology, distribution
      and evolution of DBM. This resource aims to help reduce the impact DBM has on
      agriculture using genomic and molecular tools. Database URL:
      http://iae.fafu.edu.cn/DBM/ 

PMID- 24434033
TI  - Pragmatic approach to nutrition in the ICU: expert opinion regarding which
      calorie protein target.
AB  - BACKGROUND & AIMS: Since the publications of the ESPEN guidelines on enteral and
      parenteral nutrition in ICU, numerous studies have added information to assist
      the nutritional management of critically ill patients regarding the recognition
      of the right population to feed, the energy-protein targeting, the route and the
      timing to start. METHODS: We reviewed and discussed the literature related to
      nutrition in the ICU from 2006 until October 2013. RESULTS: To identify safe,
      minimal and maximal amounts for the different nutrients and at the different
      stages of the acute illness is necessary. These amounts might be specific for
      different phases in the time course of the patient's illness. The best approach
      is to target the energy goal defined by indirect calorimetry. High protein intake
      (1.5 g/kg/d) is recommended during the early phase of the ICU stay, regardless of
      the simultaneous calorie intake. This recommendation can reduce catabolism. Later
      on, high protein intake remains recommended, likely combined with a sufficient
      amount of energy to avoid proteolysis. CONCLUSIONS: Pragmatic recommendations are
      proposed to practically optimize nutritional therapy based on recent
      publications. However, on some issues, there is insufficient evidence to make
      expert recommendations.

PMID- 24434034
TI  - Risk factors for febrile neutropenia among patients with cancer receiving
      chemotherapy: A systematic review.
AB  - Neutropenia with fever (febrile neutropenia [FN]) is a serious consequence of
      myelosuppressive chemotherapy that usually results in hospitalization and the
      need for intravenous antibiotics. FN may result in dose reductions, delays, or
      even discontinuation of chemotherapy, which, in turn, may compromise patient
      outcomes. It is important to identify which patients are at high risk for
      developing FN so that patients can receive optimal chemotherapy while their risk
      for FN is appropriately managed. A systematic review of the literature was
      performed to gain a comprehensive and updated understanding of FN risk factors.
      Older age, poor performance status, advanced disease, certain comorbidities, low
      baseline blood cell counts, low body surface area/body mass index, treatment with
      myelosuppressive chemotherapies, and specific genetic polymorphisms correlated
      with the risk of developing FN. Albeit many studies have analyzed FN risk
      factors, there are several limitations, including the retrospective nature and
      small sample sizes of most studies.

PMID- 24434035
TI  - Split WHO in two: strengthening political decision-making and securing
      independent scientific advice.
AB  - The World Health Organization (WHO) has never fulfilled its original mission of
      simultaneously serving as the world's pre-eminent public health authority and
      intergovernmental platform for global health negotiations. While WHO's
      secretariat works hard to fulfill both functions, it is undermined by an
      institutional design that mixes technical and political mandates. This forces
      staff to walk uncomfortably along many fine lines: advising but never directing;
      guiding but never governing; leading but never advocating; evaluating but never
      judging. The result is mediocrity on both fronts. Instead, WHO should be split in
      two, separating its technical and political stewardship functions into separate
      entities, with collaboration in areas of overlap. The Executive Board and
      secretariat would be bifurcated, with technical units reporting to a Technical
      Board and political units reporting to a Political Board. Both boards would
      report to the World Health Assembly where all member states would continue to
      provide ultimate oversight. Such bold changes can be implemented either by
      revising WHO's constitution or through simpler mechanisms. Either way, structural
      governance reforms would need to be accompanied by complementary changes in
      culture that support strengthened political decision-making and scientific
      independence. States' inability to act on WHO's institutional design challenges
      will only lead them and non-state actors to continue bypassing the organization
      through the creation of new entities as they have done over the last 15 years.
      The key will be to mobilize those advocates and decision-makers who have the
      audacity to demand more from WHO and convince member states to elevate their
      ambitions in current WHO reform efforts. Continued progress in global health
      depends on it. 

PMID- 24434036
TI  - Advanced imaging techniques for the study of plant growth and development.
AB  - A variety of imaging methodologies are being used to collect data for
      quantitative studies of plant growth and development from living plants. Multi
      level data, from macroscopic to molecular, and from weeks to seconds, can be
      acquired. Furthermore, advances in parallelized and automated image acquisition
      enable the throughput to capture images from large populations of plants under
      specific growth conditions. Image-processing capabilities allow for 3D or 4D
      reconstruction of image data and automated quantification of biological features.
      These advances facilitate the integration of imaging data with genome-wide
      molecular data to enable systems-level modeling. 

PMID- 24434037
TI  - Impulse control disorder in patients with Parkinson's disease under dopamine
      agonist therapy: a multicentre study.
AB  - BACKGROUND: Impulse control disorders (ICDs) encompass a wide spectrum of
      abnormal behaviour frequently found in cases of Parkinson's disease (PD) treated
      with dopamine agonists (DAs). The main aim of this study was to analyse ICD
      prevalence with different DAs. METHODS: We carried out a multicentre transversal
      study to evaluate the presence of ICDs in patients with PD chronically treated
      (>6 months) with a single non-ergolinic DA (pramipexole, ropinirole, or
      rotigotine). Clinical assessment of ICD was performed using the Questionnaire for
      Impulsive-Compulsive Disorders in Parkinson's disease. RESULTS: Thirty-nine per
      cent of patients (91/233) fulfilled the clinical criteria for ICD. The group of
      patients with ICD symptoms (ICD+) differed from those without ICD symptoms (ICD-)
      in younger age and type of DA intake. Oral DA treatment (pramipexole and
      ropinirole) was associated with higher risk of ICDs compared with transdermal DA
      (rotigotine): 84/197 (42%) patients treated with oral DA developed ICD, versus
      7/36 (19%) patients treated with transdermal DA (Fisher's exact text <0.01). In
      univariate analysis, a younger age (p<0.01), treatment with rasagiline (p<0.05),
      and especially treatment with an oral DA (pramipexole or ropinirole) (p<0.01)
      were significantly associated with ICD. Multivariate analysis confirmed that oral
      DA remained significantly associated with ICD (p: 0.014, OR: 3.14; 1.26-7.83).
      CONCLUSIONS: ICD was significantly associated with the use of the non-ergolinic
      oral DA (pramipexole and ropinirole) when compared with transdermal non-ergolinic
      DA (rotigotine). Since pramipexole, ropinirole and rotigotine are non-ergolinic
      DAs with very similar pharmacodynamic profiles, it is likely that other factors
      including route of administration (transdermal vs oral) explain the difference in
      risk of ICD development.

PMID- 24434038
TI  - Gynecologic tumors: how to communicate imaging results to the surgeon.
AB  - Gynecologic cancers are a leading cause of morbidity and mortality for female
      patients, with an estimated 88,750 new cancer cases and 29,520 deaths in the
      United States in 2012. To offer the best treatment options to patients it is
      important that the radiologist, surgeon, radiation oncologist, and gynecologic
      oncologist work together with a multidisciplinary approach. Using the available
      diagnostic imaging modalities, the radiologist must give appropriate information
      to the surgeon in order to plan the best surgical approach and its timing. 

PMID- 24434039
TI  - Reduced thymic output in elite athletes.
AB  - Athletes undergoing intensive training schedules have chronic exposure to stress
      induced hormones such as cortisol that can depress immune function. We compared
      the circulating levels of T cell receptor excision circles (TREC), a marker of
      recent thymic emigrants, as well as the levels of naive and memory subsets in a
      group of elite endurance athletes and in controls. The athletes showed a
      reduction in absolute numbers of naive T cells, particularly in CD4 T cells. In
      contrast, memory cells were increased. TREC levels in the athletes were
      significantly reduced compared to age-matched controls. Such changes resemble
      premature ageing of the T cell component of the immune system. Since thymic
      production of T cells naturally decline with age, these results raise the concern
      that prolonging high intensity exercise into the 4th decade of life may have
      deleterious consequences for athletes' health. 

PMID- 24434040
TI  - Effect of exercise training on skeletal muscle cytokine expression in the
      elderly.
AB  - Aging is associated with increased circulating pro-inflammatory and lower anti
      inflammatory cytokines. Exercise training, in addition to improving muscle
      function, reduces these circulating pro-inflammatory cytokines. Yet, few studies
      have evaluated changes in the expression of cytokines within skeletal muscle
      after exercise training. The aim of the current study was to examine the
      expression of cytokines both at rest and following a bout of isokinetic exercise
      performed before and after 12weeks of resistance exercise training in young (n=8,
      20.3+/-0.8yr) and elderly men (n=8, 66.9+/-1.6yr). Protein expression of various
      cytokines was determined in muscle homogenates. The expression of MCP-1, IL-8 and
      IL-6 (which are traditionally classified as 'pro-inflammatory') increased
      substantially after acute exercise. By contrast, the expression of the anti
      inflammatory cytokines IL-4, IL-10 and IL-13 increased only slightly (or not at
      all) after acute exercise. These responses were not significantly different
      between young and elderly men, either before or after 12weeks of exercise
      training. However, compared with the young men, the expression of pro
      inflammatory cytokines 2h post exercise tended to be greater in the elderly men
      prior to training. Training attenuated this difference. These data suggest that
      the inflammatory response to unaccustomed exercise increases with age.
      Furthermore, regular exercise training may help to normalize this inflammatory
      response, which could have important implications for muscle regeneration and
      adaptation in the elderly. 

PMID- 24434041
TI  - Dysfunctional decision-making in pathological gambling: pattern specificity and
      the role of impulsivity.
AB  - Dysfunctional decision-making in individuals with pathological gambling (PGs) may
      result from dominating reward-driven processes, indicated by higher impulsivity.
      In the current study we examined (1) if PGs show specific decision-making
      impairments related to dominating reward-driven processes rather than to
      strategic planning deficits and (2) whether these impairments are related to
      impulsivity. Nineteen PGs according to DSM-IV and 19 matched control subjects
      undertook the Cambridge Gambling Task (CGT) to assess decision-making. The delay
      discounting paradigm (DDP) as well as the UPPS Impulsive Behavior Scale
      (measuring urgency, premeditation, perseverance and sensation seeking) were
      administered as multidimensional measures of impulsivity. Results revealed that
      (1) PGs exhibited higher risk seeking and an immediate reward focus in the CGT
      and, in contrast, comparable strategic planning to the control group. (2)
      Decision-making impairments were related to more severe delay discounting and,
      specifically, to increased urgency and less premeditation. Our findings suggest
      (1) the necessity to disentangle decision-making components in order to improve
      etiological models of PGs, and (2) that urgency and premeditation are
      specifically related to disadvantageous decision-making and should be tackled in
      intervention strategies focusing on emotion tolerance and control strategies. 

PMID- 24434042
TI  - Training mode's influences on the relationships between training-load models
      during basketball conditioning.
AB  - PURPOSE: To compare perceptual and physiological training-load responses during
      various basketball training modes. METHODS: Eight semiprofessional male
      basketball players (age 26.3 +/- 6.7 y, height 188.1 +/- 6.2 cm, body mass 92.0
      +/- 13.8 kg) were monitored across a 10-wk period in the preparatory phase of
      their training plan. Player session ratings of perceived exertion (sRPE) and
      heart-rate (HR) responses were gathered across base, specific, and tactical/game
      play training modes. Pearson correlations were used to determine the
      relationships between the sRPE model and 2 HR-based models: the training impulse
      (TRIMP) and summated HR zones (SHRZ). One-way ANOVAs were used to compare
      training loads between training modes for each model. RESULTS: Stronger
      relationships between perceptual and physiological models were evident during
      base (sRPE-TRIMP r = .53, P < .05; sRPE-SHRZ r = .75, P < .05) and tactical/game
      play conditioning (sRPE-TRIMP r = .60, P < .05; sRPE-SHRZ r = .63; P < .05) than
      during specific conditioning (sRPE-TRIMP r = .38, P < .05; sRPE-SHRZ r = .52; P <
      .05). Furthermore, the sRPE model detected greater increases (126-429 AU) in
      training load than the TRIMP (15-65 AU) and SHRZ models (27-170 AU) transitioning
      between training modes. CONCLUSIONS: While the training-load models were
      significantly correlated during each training mode, weaker relationships were
      observed during specific conditioning. Comparisons suggest that the HR-based
      models were less effective in detecting periodized increases in training load,
      particularly during court-based, intermittent, multidirectional drills. The
      practical benefits and sensitivity of the sRPE model support its use across
      different basketball training modes.

PMID- 24434043
TI  - Predictors of IV behaviors during and after the 2009 influenza pandemic in
      France.
AB  - BACKGROUND: Controversies about the 2009 H1N1 pandemic influenza vaccination
      might have impacted the motivational processes that underlie individual
      immunization against seasonal influenza. The purpose of this article is to
      investigate correlates of vaccine uptake during and after the pandemic. METHODS:
      Data from the 1174 subjects of the CoPanFlu France cohort aged 15 and over were
      used. We used logistic regression models to identify social and behavioral
      predictors of getting vaccinated against seasonal influenza in 2009-2010 and in
      2010-2011 and against H1N1 influenza in 2009-2010. RESULTS: This study points out
      that correlates of vaccination behaviors varied according to the vaccine.
      Respondents under 65 years who adopted the seasonal influenza vaccine were, as
      usual, more likely to belong to a target group and have a lower education,
      contrary to subjects who chose the pandemic vaccine. Exceptionally during the
      pandemic, a higher socioeconomic status also led to adoption of either vaccine.
      Motivational processes differed by vaccine. Uptaking the "new" pandemic vaccine
      was the result of a deliberative decision-making process, influenced by cognitive
      factors related to the pandemic context (such as perceived severity of the H1N1
      flu strain and trust in public health authorities). In contrast, respondents got
      the seasonal flu vaccine without relying on explicit justifications, but instead
      through habit of performing this behavior in the past. CONCLUSIONS: Target groups
      for seasonal influenza but not those for pandemic influenza were more likely to
      adopt the pandemic vaccine, which is a cause for great concern. This may be due
      to large extent to the automatic and habitual nature of influenza vaccination
      decisions. Public health authorities, should pay more attention to situational
      than informational cues to facilitate vaccine uptake among priority groups,
      especially in case of mild pandemic influenza.

PMID- 24434044
TI  - Sublingual immunization with a subunit influenza vaccine elicits comparable
      systemic immune response as intramuscular immunization, but also induces local
      IgA and TH17 responses.
AB  - Influenza is a vaccine-preventable disease that remains a major health problem
      world-wide. Needle and syringe are still the primary delivery devices, and
      injection of liquid vaccine into the muscle is still the primary route of
      immunization. Vaccines could be more convenient and effective if they were
      delivered by the mucosal route. Elicitation of systemic and mucosal innate and
      adaptive immune responses, such as pathogen neutralizing antibodies (including
      mucosal IgA at the site of pathogen entry) and CD4(+) T-helper cells (especially
      the Th17 subset), have a critical role in vaccine-mediated protection. In the
      current study, a sublingual subunit influenza vaccine formulated with or without
      mucosal adjuvant was evaluated for systemic and mucosal immunogenicity and
      compared to intranasal and intramuscular vaccination. Sublingual administration
      of adjuvanted influenza vaccine elicited comparable antibody titers to those
      elicited by intramuscular immunization with conventional influenza vaccine.
      Furthermore, influenza-specific Th17 cells or neutralizing mucosal IgA were
      detected exclusively after mucosal immunization. 

PMID- 24434045
TI  - Rabies: underused vaccines, unnecessary deaths.

PMID- 24434046
TI  - Trend in proportions of missed children during polio supplementary immunization
      activities in the African Region: evidence from independent monitoring data 2010
      2012.
AB  - This is a comparative analysis of independent monitoring data collected between
      2010 and 2012, following the implementation of supplementary immunization
      activities (SIAs) in countries in the three sub regional blocs of World Health
      Organization in the African Region. The sub regional blocs are Central Africa,
      West Africa, East and Southern Africa. In addition to the support for SIAs, the
      Central and West African blocs, threatened with importation and re-establishment
      of polio transmission received intensive coordination through weekly
      teleconferences. The later, East and Southern African bloc with low polio threats
      was not engaged in the intensive coordination through teleconferences. The key
      indicator of the success of SIAs is the proportion of children missed during
      SIAs. The results showed that generally there was a decrease in the proportion of
      children missed during SIAs in the region, from 7.94% in 2010 to 5.95% in 2012.
      However, the decrease was mainly in the Central and West African blocs. The East
      and Southern African bloc had countries with as much as 25% missed children. In
      West Africa and Central Africa, where more coordinated SIAs were conducted, there
      were progressive and consistent drops, from close to 20-10% at the maximum. At
      the country and local levels, steps were undertaken to ameliorate situation of
      low immunization uptake. Wherever an area is observed to have low coverage, local
      investigations were conducted to understand reasons for low coverage, plans to
      improve coverage are made and implemented in a coordinated manner. Lessons
      learned from close monitoring of polio eradication SIAs are will be applied to
      other campaigns being conducted in the African Region to accelerate control of
      other vaccine preventable diseases including cerebrospinal meningitis A, measles
      and yellow fever. 

PMID- 24434047
TI  - The role of molecular imaging in modern drug development.
AB  - Drug development represents a highly complex, inefficient and costly process.
      Over the past decade, the widespread use of nuclear imaging, owing to its
      functional and molecular nature, has proven to be a determinant in improving the
      efficiency in selecting the candidate drugs that should either be abandoned or
      moved forward into clinical trials. This helps not only with the development of
      safer and effective drugs but also with the shortening of time-to-market. The
      modern concept and future trends concerning molecular imaging will assumedly be
      hybrid or multimodality imaging, including combinations between high sensitivity
      and functional (molecular) modalities with high spatial resolution and
      morphological techniques.

PMID- 24434048
TI  - End-of-life preferences and presence of advance directives among ethnic
      populations with severe chronic cardiovascular illnesses.
AB  - BACKGROUND: Little end-of-life planning occurs among ethnic minorities with
      severe cardiovascular illnesses. AIM: The purpose of this study was to explore
      end-of-life preferences and determine the presence of signed end-of-life advanced
      directives. METHODS: Thirty ethnic minority patients volunteered for an open
      ended question interview. Content analysis was used to summarize responses into
      themes using patients' terms. FINDINGS: Five themes emerged: (a) importance of
      family involvement in care at end of life; (b) being pain free (or pain
      controlled) at the end of life; (c) having a comfortable environment for death
      was desired; (d) wanting no procedures for prolonging life; and (e) desiring a
      relationship with a professional for end-of-life decision making (reported as
      inconsistently available). New unique findings were related to concerns about
      multiple and repeatedly rotating professionals not allowing these ethnic patients
      end-of-life discussions and fear that signing forms would lead to deportation.
      Overall, 50% of the participants had signed standard advanced directives as
      requested upon entry to the home care agency. CONCLUSIONS: Most of these very ill
      patients did readily discuss these sensitive issues with the research nurse.
      Cardiovascular training in end-of-life care should include sensitivity to ethnic
      and cultural preferences and competencies in interviewing on sensitive topics.

PMID- 24434049
TI  - Development of a practice tool for community-based nurses: the Heart Failure
      Palliative Approach to Care (HeFPAC).
AB  - BACKGROUND: Patients living with advanced heart failure (HF) require a palliative
      approach to reduce suffering. Nurses have described significant knowledge gaps
      about the disease-specific palliative care (PC) needs of these patients. An
      intervention is required to facilitate appropriate end-of-life care for HF
      patients. AIMS: The purpose of this study was to develop a user-friendly,
      evidence-informed HF-specific practice tool for community-based nurses to
      facilitate care and communication regarding a palliative approach to HF care.
      METHODS: Guided by the Knowledge to Action framework, we identified key HF
      specific issues related to advanced HF care provision within the context of a
      palliative approach to care. Informed by current evidence and subsequent
      iterative consultation with community-based and specialist PC and HF nurses, a
      pocket guide tool for community-based nurses was created. RESULTS: We developed
      the Heart Failure Palliative Approach to Care (HeFPAC) pocket guide to promote
      communication and a palliative approach to care for HF patients. The HeFPAC has
      potential to improve the quality of care and experiences for patients with
      advanced HF. It will be piloted in community-based practice and in a continuing
      education program for nurses. CONCLUSION: The HeFPAC pocket guide offers PC
      nurses a concise, evidence-informed and practical point-of care tool to
      communicate with other clinicians and patients about key HF issues that are
      associated with improving disease-specific HF palliative care and the quality of
      life of patients and their families. Pilot testing will offer insight as to its
      utility and potential for modification for national and international use.

PMID- 24434050
TI  - Self-reported health status in coronary heart disease patients: a comparison with
      the general population.
AB  - BACKGROUND: The aim of our study was to compare Euroqol-5D (EQ-5D) outcomes in
      coronary heart disease (CHD) patients with those from the general population. We
      aimed to identify those dimensions which were mostly impaired. METHODS: EQ-5D
      results (both the dimensions and the EQ-5D visual analogue scale (EQ-VAS)) from a
      European sample (11 countries) of coronary patients were compared with published
      age- and gender-specific normative data. RESULTS: EQ-5D outcomes differed across
      countries and gender. Overall, the age-adjusted EQ-VAS scores were significantly
      lower in coronary patients compared with the general population, both in males
      (mean difference (MD)= -5.24(-7.59 to -2.88)) and in females (MD= -8.32 (-11.69
      to -4.95)). Coronary patients had a significantly higher risk to report moderate
      or severe problems related to anxiety/depression (odds ratio (OR) male=1.84 (1.14
      2.95); OR female=3.20 (2.32-4.40)). Furthermore, female coronary patients
      reported more problems on the mobility (OR=2.00 (1.38-2.90)), usual activity (OR=
      2.54 (1.81-3.57)) and pain/discomfort dimension (OR=1.73 (1.23-2.43)) whereas in
      males, a borderline significant OR was found on the mobility (OR=1.43 (0.97
      2.11)) and usual activity dimension (OR=1.44 (0.94-2.20)). The difference between
      the general population and the CHD patients attenuated as age increased.
      CONCLUSIONS: CHD has a negative influence on patient's self-reported health
      status, both the EQ-VAS as well as the EQ-5D dimensions (with the exception of
      self-care in both genders and pain/discomfort in males) were impaired. The
      relative impairment was the greatest in female patients and the differences in
      the proportion of reported problems diminished with increasing age. The EQ-5D
      instrument is appropriate in capturing problems related to anxiety/depression,
      pain/discomfort, mobility and usual activities. Within clinical practice,
      particular attention should be given to females and younger CHD patients.

PMID- 24434052
TI  - Are we seeing the effects of public awareness campaigns? A 10-year analysis of
      Breslow thickness at presentation of malignant melanoma in the South West of
      England.
AB  - INTRODUCTION: The last 20 years has seen a marked improvement in skin cancer
      awareness campaigns. We sought to establish whether this has affected the
      presenting Breslow thickness of malignant melanoma in the South West. METHOD:
      This is a retrospective study looking at the first presentation of melanomas from
      2003 to 2011. Data was accessed using the local online melanoma database.
      RESULTS: A total of 2001 new melanomas presented from 2003 to 2012 (Male:Female =
      1:1.062). The average yearly number of melanomas was 200.1 (range = 138-312). The
      mean age was 62.5 years (range 12-99). Data was analysed using a Chi2 test. For 0
      1 mm melanomas, there is a significant difference in the observed versus expected
      values over the 10 years (p = 0.0018). There is an increasing proportion of 0-1
      mm (thin) melanomas presenting year on year, with a positive linear trend. This
      is very statistically significant (p < 0.0001). The 1-2 mm melanomas are
      decreasing in proportion with a negative linear trend (p = 0.0013). The 2-4 mm
      are also decreasing in proportion (p = 0.0253). There is no significant change in
      the thick >4 mm melanomas (p = 0.1456). CONCLUSION: The proportion of thin 0-1 mm
      melanomas presenting in South West England has significantly increased from 2003
      to 2012. There is no significant change in the thick >4 mm melanomas. This may be
      a result of increased public awareness due to effective public health campaigns
      which has significant prognostic and financial implications.

PMID- 24434051
TI  - Factors associated with perceived control and the relationship to quality of life
      in patients with heart failure.
AB  - BACKGROUND AND PURPOSE: Health-related quality of life (HRQOL) is as important as
      survival to patients with heart failure (HF). Perceptions of loss of control are
      common in HF and negatively affect HRQOL. Knowledge of modifiable factors
      associated with perceived control could guide the development of interventions to
      improve perceived control and thus HRQOL. Accordingly, this study examined
      factors related to perceived control and the relationship between perceived
      control and HRQOL. METHODS: Patients (N=232, mean age 61 +/- 12, 67% male, 78%
      Caucasian) provided data on HRQOL (Minnesota Living with Heart Failure
      questionnaire), perceived control (Control Attitudes Scale-Revised), and factors
      possibly associated with perceived control (knowledge and barriers (Heart Failure
      Knowledge and Barriers to Adherence Scale), attitudes (Dietary Sodium Restriction
      Questionnaire), and social support (Multidimensional Scale of Perceived Social
      Support)). Patients also provided data on depressive symptoms, which were a
      covariate of HRQOL. Hierarchical multiple regression analysis was used to analyze
      the data. RESULTS: Fewer barriers to following a low sodium diet, more positive
      attitudes toward following a low sodium diet, and better social support were
      related to higher perceived control (F=7.54, R(2)=0.17, p<0.001). Perceived
      control was independently associated with HRQOL, controlling for depressive
      symptoms, New York Heart Association functional class, age, gender, and all
      variables possibly associated with perceived control (F=29.67, R(2)=0.55,
      p<0.001). CONCLUSIONS: Interventions targeting attitudes and barriers to a low
      sodium diet and social support may improve perceived control and, in turn, HRQOL.

PMID- 24434053
TI  - "Out of our control": living through Cyclone Yasi.
AB  - The aim of this study was to explore the experiences of people who lived through
      Cyclone Yasi on 3 February 2011. Data from two open-ended questions (Q1: n=344;
      and Q2: n=339) within a survey completed by 433 residents of cyclone-affected
      areas between Cairns and Townsville, Australia, were analysed using a
      qualitative, thematic approach. Experiences were portrayed in three main themes:
      (1) living in the mode of existential threat describes survivors' sense of panic
      and feeling at the mercy of nature as they feared for their life; (2)
      unforgettable memories describe feelings of emotional helplessness and the
      unimaginable chaos that the cyclone wrought; and (3) centrality of others shows
      how community support and closeness helped alleviate losses and uncertainty. A
      critical finding from this study was the negative role of the media in escalating
      fears for life prior to and during the cyclone, highlighting the need for
      government, community leaders, and health professionals to have a media plan in
      place to ensure that disaster warnings are taken seriously without inciting
      unnecessary panic. Although survivors experienced extreme vulnerability and a
      threat to life, the disaster also brought communities closer together and
      connected family, friends, and neighbours through the caring, support, and help
      they offered each other. This highlights the central role of others during the
      recovery process and underlines the importance of promoting and facilitating
      social support to aid recovery post disaster. 

PMID- 24434054
TI  - South African managers in public service: on being authentic.
AB  - South African managers in public service consistently face challenges related to
      managing a well-adjusted and productive diverse workforce. Following the notion
      that leadership authenticity fosters positive psychological employee capacity,
      the aim of this study was to explore the meaning essence of authenticity as lived
      in the work-life experiences of senior managers in public service. Five senior
      managers in public service were purposefully selected based on their articulated
      challenges with being authentic at work, whilst attending a diversity sensitivity
      workshop. From a hermeneutic phenomenological perspective, in-depth interviews
      were used, and an interpretative phenomenological analysis yielded two
      predominant themes offering a description of what it means to be authentic.
      Authenticity is experienced as an affective state that results from a continuous
      self-appraisal of the extent to which expression of self is congruent with a
      subjective and socially constructed expectation of self in relation to others.
      Authenticity seems to develop through a continuous process of internal and
      external adaptation, and it leads to ultimately building a differentiated yet
      integrated identity of self. A reciprocal dynamic between feeling authentic and
      self-confidence alludes to the potential importance of authenticity dynamics in
      identity work. 

PMID- 24434055
TI  - Medical yoga: another way of being in the world-a phenomenological study from the
      perspective of persons suffering from stress-related symptoms.
AB  - The prevalence of stress-related illness has grown in recent years. Many of these
      patients seek help in primary health care. Yoga can reduce stress and thus
      complements pharmacological therapy in medical practice. To our knowledge, no
      studies have investigated patients' experiences of yoga treatment in a primary
      health care setting or, specifically, the experiences of yoga when suffering from
      stress-related illness. Thus, the aim of the present study was to explore the
      meaning of participating in medical yoga as a complementary treatment for stress
      related symptoms and diagnosis in a primary health care setting. This study has a
      descriptive phenomenological design and took place at a primary health care
      centre in Sweden during 2011. Five women and one man (43-51 years) participated.
      They were recruited from the intervention group (n=18) in a randomized control
      trial, in which they had participated in a medical yoga group in addition to
      standard care for 12 weeks. Data were collected by means of qualitative
      interviews, and a phenomenological data analysis was conducted. The essential
      meaning of the medical yoga experience was that the medical yoga was not an
      endpoint of recovery but the start of a process towards an increased sense of
      wholeness. It was described as a way of alleviating suffering, and it provided
      the participants with a tool for dealing with their stress and current situation
      on a practical level. It led to greater self-awareness and self-esteem, which in
      turn had an implicit impact on their lifeworld. In phenomenological terms, this
      can be summarized as Another way of being in the world, encompassing a perception
      of deepened identity. From a philosophical perspective, due to using the body in
      a new way (yoga), the participants had learnt to see things differently, which
      enriched and recast their perception of themselves and their lives. 

PMID- 24434056
TI  - Safety, bioavailability and mechanism of action of nitric oxide to control Bovine
      Respiratory Disease Complex in calves entering a feedlot.
AB  - Bovine Respiratory Disease Complex (BRDc), a multi-factorial disease, negatively
      impacts the cattle industry. Nitric oxide (NO), a naturally occurring molecule,
      may have utility controlling incidence of BRDc. Safety, bioavailability,
      toxicology and tolerance/stress of administering NO to cattle is evaluated
      herein. Thirteen, crossbred, multiple-sourced, commingled commercial weaned beef
      calves were treated multiple times intranasally over a 4 week period with either
      a nitric oxide releasing solution (treatment) or saline (control). Exhaled NO,
      methemoglobin percent (MetHg) and serum nitrites demonstrated biological
      availability as a result of treatment. Cortisol levels, tissue nitrites, behavior
      and gross and macroscopic pathology of organs were all normal. Moreover,
      preliminary in vitro studies using Mannheimia haemolytica, Infectious Bovine
      Rhinotracheitis, Bovine Parainfluenza-3 and Bovine Respiratory Syncytial Virus,
      suggest a potential explanation for the previously demonstrated efficacy for
      BRDc. These data confirm the bioavailability, safety and lack of residual of NO
      treatment to cattle, along with the bactericidal and virucidal effects.

PMID- 24434057
TI  - Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: a
      histologic dichotomy.
AB  - BACKGROUND: Treatment failures in stage IIIC endometrial carcinoma (EC) are
      predominantly due to occult extrapelvic metastases (EPM). The impact of
      chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs
      G3EC. METHODS: All surgical-stage IIIC EC cases from January 1, 1999, through
      December 31, 2008, from Mayo Clinic were included. Patient-, disease-, and
      treatment-specific risk factors were assessed for association with overall
      survival, cause-specific survival, and extrapelvic disease-free survival (DFS)
      using Cox proportional hazards regression. RESULTS: 109 cases met criteria, with
      92 (84%) having systematic lymphadenectomy (>10 pelvic and >5 paraaortic lymph
      nodes resected). In patients with documented recurrence sites, occult EPM
      accounted for 88%. Among G1/2EC cases (n=48), the sole independent predictor of
      extrapelvic DFS was grade 2 histology (hazard ratio [HR], 0.28; 95% CI, 0.08
      0.91; P=.03) while receipt of adjuvant chemotherapy approached significance (HR
      0.13; 95% CI, 0.02, 1.01; P=.0511). The 5-year extrapelvic DFS with and without
      adjuvant chemotherapy was 93% and 54%, respectively (log-rank, P=.02). Among G3EC
      (n=61), the sole independent predictor of extrapelvic DFS was lymphovascular
      space involvement (HR, 2.63; 95% CI, 1.16-5.97; P=.02). Adjuvant chemotherapy did
      not affect occult EPM in G3EC; the 5-year extrapelvic DFS for G3EC with and
      without adjuvant chemotherapy was 43% and 42%, respectively (log-rank, P=.91).
      CONCLUSIONS: Chemotherapy improves extrapelvic DFS for stage IIIC G1/2EC but not
      stage IIIC G3EC. Future efforts should focus on prospectively assessing the
      impact of chemotherapy on DFS in G3EC and developing innovative phase I and II
      trials of novel systemic therapies for advanced G3EC.

PMID- 24434058
TI  - Oncolytic vaccinia virotherapy for endometrial cancer.
AB  - OBJECTIVE: Oncolytic virotherapy is a promising modality in endometrial cancer
      (EC) therapy. In this study, we compared the efficacy of the Copenhagen and Wyeth
      strains of oncolytic vaccinia virus (VV) incorporating the human thyroidal sodium
      iodide symporter (hNIS) as a reporter gene (VVNIS-C and VVNIS-W) in EC. METHODS:
      Infectivity of VVNIS-C and VVNIS-W in type I (HEC1A, Ishikawa, KLE, RL95-2, and
      AN3 CA) and type II (ARK-1, ARK-2, and SPEC-2) human EC cell lines was evaluated.
      Athymic mice with ARK-2 or AN3 CA xenografts were treated with one intravenous
      dose of VVNIS-C or VVNIS-W. Tumor regression and in vivo infectivity were
      monitored via NIS expression using SPECT-CT imaging. RESULTS: All EC cell lines
      except KLE were susceptible to infection and killing by VVNIS-C and VVNIS-W in
      vitro. VVNIS-C had higher infectivity and oncolytic activity than VVNIS-W in all
      cell lines, most notably in AN3 CA. Intravenous VVNIS-C was more effective at
      controlling AN3 CA xenograft growth than VVNIS-W, while both VVNIS-C and VVNIS-W
      ceased tumor growth and induced tumor regression in 100% of mice bearing ARK-2
      xenografts. CONCLUSION: Overall, VVNIS-C has more potent oncolytic viral activity
      than VVSIN-W in EC. VV appears to be most active in type II EC. Novel therapies
      are needed for the highly lethal type II EC histologies and further development
      of a VV clinical trial in type II EC is warranted.

PMID- 24434059
TI  - MEK1/2 inhibitors in the treatment of gynecologic malignancies.
AB  - Mitogen-activated protein kinases (MAPKs) are a family of ubiquitous eukaryotic
      signal transduction enzymes which link extracellular stimuli to intracellular
      gene expression pathways. While several three-tiered MAPK cascades have been
      elucidated in mammals, the prototypical pathway involves a network of proteins
      and kinases including the Rat sarcoma protein (Ras), mitogen-activated protein
      kinase kinase kinase (Raf or MAP3K), mitogen-activated protein kinase kinase (MEK
      or MAP2K), and extracellular signal regulated protein kinase (ERK or MAPK). This
      MAPK cascade (the Ras/Raf/MEK/ERK pathway) is a receptor tyrosine kinase mediated
      signaling pathway that regulates cell proliferation, cell cycle progression, and
      cell migration. There are multiple molecular mechanisms of interaction and
      activation between the upstream nodes of the Ras/Raf/MEK/ERK cascade and other
      cell signaling pathways, all ultimately leading to the activation of the nuclear
      transcription factor ERK. Important downstream targets include MEK1/2, which
      comprise the final step leading to ERK transcription factor activation. While
      multiple conduits exist to activate ERK upstream of MEK, there is little
      redundancy downstream. Located at this pivotal intersection between a limited
      number of upstream activators and its exclusive downstream targets, MEK is an
      appealing molecular target of novel cancer therapies. MEK inhibitors are small
      molecules that inhibit MEK phosphorylation by binding to a pocket adjacent to the
      ATP binding site, decreasing both the amount of MEK activity, and the quantity of
      activated ERK in the cell. Unique allosteric noncompetitive binding sites of MEK
      inhibitors allow specific targeting of MEK enzymes and prevent cross-activation
      of other serine/threonine protein kinases through the conserved ATP binding site.
      This paper reviews the translational evidence in favor of MEK inhibitors in
      cancer, their role in gynecologic malignancies, and details regarding the status
      of the fourteen MEK inhibitors currently being clinically tested: trametinib,
      selumetinib, pimasertib, refametinib, PD-0325901, MEK162, TAK733, RO5126766, WX
      554, RO4987655, cobimetinib, AZD8330, MSC2015103B, and ARRY-300.

PMID- 24434060
TI  - Effects of gangliosides on the activity of the plasma membrane Ca2+-ATPase.
AB  - Control of intracellular calcium concentrations ([Ca(2+)]i) is essential for
      neuronal function, and the plasma membrane Ca(2+)-ATPase (PMCA) is crucial for
      the maintenance of low [Ca(2+)]i. We previously reported on loss of PMCA activity
      in brain synaptic membranes during aging. Gangliosides are known to modulate
      Ca(2+) homeostasis and signal transduction in neurons. In the present study, we
      observed age-related changes in the ganglioside composition of synaptic plasma
      membranes. This led us to hypothesize that alterations in ganglioside species
      might contribute to the age-associated loss of PMCA activity. To probe the
      relationship between changes in endogenous ganglioside content or composition and
      PMCA activity in membranes of cortical neurons, we induced depletion of
      gangliosides by treating neurons with d-threo-1-phenyl-2-decanoylamino-3
      morpholino-1-propanol (d-PDMP). This caused a marked decrease in the activity of
      PMCA, which suggested a direct correlation between ganglioside content and PMCA
      activity. Neurons treated with neuraminidase exhibited an increase in GM1
      content, a loss in poly-sialoganglioside content, and a decrease in PMCA activity
      that was greater than that produced by d-PDMP treatment. Thus, it appeared that
      poly-sialogangliosides had a stimulatory effect whereas mono-sialogangliosides
      had the opposite effect. Our observations add support to previous reports of PMCA
      regulation by gangliosides by demonstrating that manipulations of endogenous
      ganglioside content and species affect the activity of PMCA in neuronal
      membranes. Furthermore, our studies suggest that age-associated loss in PMCA
      activity may result in part from changes in the lipid environment of this Ca(2+)
      transporter. 

PMID- 24434061
TI  - System A amino acid transporter SNAT2 shows subtype-specific affinity for betaine
      and hyperosmotic inducibility in placental trophoblasts.
AB  - Betaine uptake is induced by hypertonic stress in a placental trophoblast cell
      line, and involvement of amino acid transport system A was proposed. Here, we
      aimed to identify the subtype(s) of system A that mediates hypertonicity-induced
      betaine uptake. Measurement of [(14)C]betaine uptake by HEK293 cells transiently
      transfected with human or rat sodium-coupled neutral amino acid transporters
      (SNATs), SNAT1, SNAT2 and SNAT4 revealed that only human and rat SNAT2 have
      betaine uptake activity. The Michaelis constants (Km) of betaine uptake by human
      and rat SNAT2 were estimated to be 5.3 mM and 4.6 mM, respectively. Betaine
      exclusively inhibited the uptake activity of SNAT2 among the rat system A
      subtypes. We found that rat SNAT1, SNAT2 and SNAT4 were expressed at the mRNA
      level under isotonic conditions, while expression of SNAT2 and SNAT4 was induced
      by hypertonicity in TR-TBT 18d-1 cells. Western blot analyses revealed that SNAT2
      expression on plasma membrane of TR-TBT 18d-1 cells was more potently induced by
      hypertonicity than that in total cell lysate. Immunocytochemistry confirmed the
      induction of SNAT2 expression in TR-TBT 18d-1 cells exposed to hypertonic
      conditions and indicated that SNAT2 was localized on the plasma membrane in these
      cells. Our results indicate that SNAT2 transports betaine, and that tonicity
      sensitive SNAT2 expression may be involved in regulation of betaine concentration
      in placental trophoblasts.

PMID- 24434062
TI  - Epithelial gp130/Stat3 functions: an intestinal signaling node in health and
      disease.
AB  - A contiguous intestinal epithelial barrier safeguards against aberrant activation
      of the immune system and therefore requires molecular mechanisms that ensure
      effective wound-healing responses. During this processes cytokine-producing
      myeloid cells serve as rheostats that link the degree of wounding and local
      inflammation to the epithelial repair response. Likewise, intestinal inflammation
      is an important factor by which the microenvironment promotes tumorigenesis and
      the progression of established cancers by facilitating neoplastic cell survival
      and proliferation. Among the cytokines and chemokines orchestrating this process,
      those comprising the interleukin (IL) IL6, IL10/IL22 and IL17/IL23 families play
      a prominent role by virtue of converging on the latent Signal Transducer and
      Activator of Transcription (Stat)-3. Accordingly, aberrant and persistent Stat3
      activation is a frequent observation in cancers of the gastrointestinal tract
      where it promotes "cancer hallmark capabilities" in the malignant epithelium and
      suppresses the anti-tumor response of innate and adaptive immune cells. Here, we
      discuss recent insights arising from situations where persistent activation of
      the gp130/Stat3 signaling cascades result from excessive abundance of IL6 family
      cytokines. In particular, we highlight novel and unique roles for IL11 in
      promoting intestinal wound-healing and, in its corrupted form, enabling and
      facilitating growth of inflammation-associated and sporadic gastrointestinal
      tumors. 

PMID- 24434064
TI  - Comment on "inflammation in the context of oral cancer" by L. Feller, M. Altini,
      J. Lemmer [Oral Oncol 2013;49(9):887-92].

PMID- 24434065
TI  - Defining 'upper mediastinal irradiation' in secondary subglottic laryngeal
      cancer.

PMID- 24434063
TI  - Toward a new STATe: the role of STATs in mitochondrial function.
AB  - Signal Transducers and Activators of Transcription (STATs) have been studied
      extensively and have been associated with virtually every biochemical pathway.
      Until recently, however, they were thought to exert these effects solely as a
      nuclear transcription factor. The finding that STAT3 localizes to the
      mitochondria and modulates respiration has opened up a new avenue through which
      STATs may regulate the cell. Recently, other members of the STAT family (STAT1,
      STAT2, STAT5, and STAT6) have also been shown to be present in the mitochondria.
      Coordinate regulation at the nucleus and mitochondria by these proteins places
      them in a unique position to drive cellular processes to achieve a specific
      response. This review summarizes recent findings that have led to our current
      understanding of how STATs influence mitochondrial function in health and
      disease. 

PMID- 24434066
TI  - Patients with HPV-related tonsil squamous cell carcinoma rarely harbour oncogenic
      HPV infection at other pharyngeal sites.
AB  - OBJECTIVES: Patients with human papillomavirus (HPV)-related oropharyngeal
      squamous cell carcinoma (OPSCC) have a reduced risk of developing second primary
      upper aerodigestive tract (UADT) tumours compared to patients with HPV-negative
      primary tumours at the same site. To determine whether this finding might be
      explained by a lack of viral-induced field cancerisation or multifocal infection,
      we investigated whether there was epithelial dysplasia and/or evidence of HPV
      infection at other pharyngeal mucosal sites in patients presenting with the
      disease. MATERIALS AND METHODS: Sixty-three patients with primary tonsil SCC and
      108 pharyngeal endoscopic biopsies, representing at least one pharyngeal subsite
      from each patient, were included in this study. Tissue samples were tested using
      HPV PCR (GP5+/6+), p16 immunohistochemistry (IHC) and high risk HPV DNA in situ
      hybridisation (ISH). RESULTS: There were 46 patients with HPV-related SCC and 17
      patients with HPV-negative disease. PCR detected HPV DNA in a fifth of pharyngeal
      endoscopic biopsies and was equally likely to be from a patient with HPV-related
      SCC as from a patient with HPV negative disease. All PCR positive cases were
      tested using p16 IHC and high risk HPV ISH and only three biopsies were positive.
      Significantly, these three biopsies all showed evidence of epithelial dysplasia
      and were from patients with an HPV positive index tumour. CONCLUSION: Our data
      suggest that virus-induced field cancerisation and/or multifocal oncogenic HPV
      infection of the pharynx is uncommon in OPSCC and supports the concept that these
      patients have a lower risk of developing second primary tumours of the UADT.

PMID- 24434067
TI  - Vanilloids induce oral cancer apoptosis independent of TRPV1.
AB  - OBJECTIVE: To investigate the mechanisms of vanilloid cytotoxicity and anti-tumor
      effects in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS:
      Immunohistochemistry and qPCR analyses demonstrated expression of the TRP
      vanilloid type 1 (TRPV1) receptor in OSCC. Using cell proliferation assays,
      calcium imaging, and three mouse xenograft models, prototypical vanilloid agonist
      (capsaicin) and antagonist (capsazepine) were evaluated for cytotoxic and anti
      tumor effects in OSCC. RESULTS: OSCC cell lines treated with capsaicin displayed
      significantly reduced cell viability. Pre-treatment with capsazepine failed to
      reverse these effects. Moreover, capsazepine alone was significantly cytotoxic to
      tumor cells, suggesting the mechanism-of-action is independent of TRPV1
      activation. This was further confirmed by calcium imaging indicating that TRPV1
      channels are not functional in the cell lines tested. We then examined whether
      the observed vanilloid cytotoxicity was due to the generation of reactive oxygen
      species (ROS) and subsequent apoptosis. Induction of ROS was confirmed by flow
      cytometry and reversed by co-treatment with the antioxidant N-acetyl-cysteine
      (NAC). NAC also significantly reversed vanilloid cytotoxicity in cell
      proliferation assays. Dose-dependent induction of apoptosis with capsazepine
      treatment was demonstrated by FACS analyses and c-PARP expression in treated
      cells. Our in vivo xenograft studies showed that intra-tumoral injections of
      capsazepine exhibited high effectiveness in suppressing tumor growth with no
      identifiable toxicities. CONCLUSIONS: These findings confirm TRPV1 channel
      expression in OSCC. However anti-tumor effects of vanilloids are independent of
      TRPV1 activation and are most likely due to ROS induction and subsequent
      apoptosis. Importantly, these studies demonstrate capsazepine is a potential
      therapeutic candidate for OSCC.

PMID- 24434069
TI  - Childhood ILD: Don't forget lymphocytic interstitial pneumonitis.

PMID- 24434068
TI  - PPARgamma in head and neck cancer prevention.
AB  - Head and neck cancer is a major source of morbidity and mortality worldwide.
      Intervention during the early phases of carcinogenesis represents a promising new
      strategy for curbing the devastating effects of this disease and its primary
      treatment modalities, surgery and radiation with or without concomitant
      chemotherapy. This review focuses on the peroxisome proliferator-activated
      receptor gamma (PPARgamma) as a target for chemoprevention of oral cancer.
      Accumulating data suggest that ligands of PPARgamma, which include the
      thiazolidinedione class of agents approved for the treatment of diabetes, inhibit
      cancer cell growth in vitro and in animal carcinogenesis models, providing the
      rationale for testing this approach in populations at risk for head and neck
      cancer. 

PMID- 24434070
TI  - Group problem-solving skills training for self-harm: randomised controlled trial.
AB  - BACKGROUND: Rates of self-harm are high and have recently increased. This trend
      and the repetitive nature of self-harm pose a significant challenge to mental
      health services. AIMS: To determine the efficacy of a structured group problem
      solving skills training (PST) programme as an intervention approach for self-harm
      in addition to treatment as usual (TAU) as offered by mental health services.
      METHOD: A total of 433 participants (aged 18-64 years) were randomly assigned to
      TAU plus PST or TAU alone. Assessments were carried out at baseline and at 6-week
      and 6-month follow-up and repeated hospital-treated self-harm was ascertained at
      12-month follow-up. RESULTS: The treatment groups did not differ in rates of
      repeated self-harm at 6-week, 6-month and 12-month follow-up. Both treatment
      groups showed significant improvements in psychological and social functioning at
      follow-up. Only one measure (needing and receiving practical help from those
      closest to them) showed a positive treatment effect at 6-week (P = 0.004) and 6
      month (P = 0.01) follow-up. Repetition was not associated with waiting time in
      the PST group. CONCLUSIONS: This brief intervention for self-harm is no more
      effective than treatment as usual. Further work is required to establish whether
      a modified, more intensive programme delivered sooner after the index episode
      would be effective.

PMID- 24434071
TI  - Mental health outcomes in US and UK military personnel returning from Iraq.
AB  - BACKGROUND: Research of military personnel who deployed to the conflicts in Iraq
      or Afghanistan has suggested that there are differences in mental health outcomes
      between UK and US military personnel. AIMS: To compare the prevalence of post
      traumatic stress disorder (PTSD), hazardous alcohol consumption, aggressive
      behaviour and multiple physical symptoms in US and UK military personnel deployed
      to Iraq. METHOD: Data were from one US (n = 1560) and one UK (n = 313) study of
      post-deployment military health of army personnel who had deployed to Iraq during
      2007-2008. Analyses were stratified by high- and low-combat exposure. RESULTS:
      Significant differences in combat exposure and sociodemographics were observed
      between US and UK personnel; controlling for these variables accounted for the
      difference in prevalence of PTSD, but not in the total symptom level scores.
      Levels of hazardous alcohol consumption (low-combat exposure: odds ratio (OR) =
      0.13, 95% CI 0.07-0.21; high-combat exposure: OR = 0.23, 95% CI 0.14-0.39) and
      aggression (low-combat exposure: OR = 0.36, 95% CI 0.19-0.68) were significantly
      lower in US compared with UK personnel. There was no difference in multiple
      physical symptoms. CONCLUSIONS: Differences in self-reported combat exposures
      explain most of the differences in reported prevalence of PTSD. Adjusting for
      self-reported combat exposures and sociodemographics did not explain differences
      in hazardous alcohol consumption or aggression.

PMID- 24434072
TI  - Psychotic traits in comedians.
AB  - BACKGROUND: The popular belief that creativity is associated with madness has
      increasingly become the focus of research for many psychologists and
      psychiatrists. However, despite being prime examples of creative thinking, comedy
      and humour have been largely neglected. AIMS: To test the hypothesis that
      comedians would resemble other creative individuals in showing a higher level of
      psychotic characteristics related to both schizophrenia and manic depression.
      METHOD: A group of comedians (n = 500+) and a control sample of actors (n = 350+)
      completed an online questionnaire containing the short version of the Oxford
      Liverpool Inventory of Feelings and Experiences (O-LIFE), with scales measuring
      four dimensions of psychotic traits. Scores were compared with general population
      norms. RESULTS: Comedians scored significantly above O-LIFE norms on all four
      scales. Actors also differed from the norms but on only three of the scales. Most
      striking was the comedians' high score on both introverted anhedonia and
      extraverted impulsiveness. CONCLUSIONS: This unusual personality structure may
      help to explain the facility for comedic performance.

PMID- 24434073
TI  - Efficacy of Coming Out Proud to reduce stigma's impact among people with mental
      illness: pilot randomised controlled trial.
AB  - BACKGROUND: Facing frequent stigma and discrimination, many people with mental
      illness have to choose between secrecy and disclosure in different settings.
      Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in
      this domain in order to reduce stigma's negative impact. AIMS: To examine COP's
      efficacy to reduce negative stigma-related outcomes and to promote adaptive
      coping styles (Current Controlled Trials number: ISRCTN43516734). METHOD: In a
      pilot randomised controlled trial, 100 participants with mental illness were
      assigned to COP or a treatment-as-usual control condition. Outcomes included self
      stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure.
      RESULTS: Intention-to-treat analyses found no effect of COP on self-stigma or
      empowerment, but positive effects on stigma stress, disclosure-related distress,
      secrecy and perceived benefits of disclosure. Some effects diminished during the
      3-week follow-up period. CONCLUSIONS: Coming Out Proud has immediate positive
      effects on disclosure- and stigma stress-related variables and may thus alleviate
      stigma's negative impact.

PMID- 24434074
TI  - Working memory networks and activation patterns in schizophrenia and bipolar
      disorder: comparison with healthy controls.
AB  - BACKGROUND: Schizophrenia and bipolar disorder are severe mental disorders with
      overlapping genetic and clinical characteristics, including cognitive
      impairments. An important question is whether these disorders also have
      overlapping neuronal deficits. AIMS: To determine whether large-scale brain
      networks associated with working memory, as measured with functional magnetic
      resonance imaging (fMRI), are the same in both schizophrenia and bipolar
      disorder, and how they differ from those in healthy individuals. METHOD: Patients
      with schizophrenia (n = 100) and bipolar disorder (n = 100) and a healthy control
      group (n = 100) performed a 2-back working memory task while fMRI data were
      acquired. The imaging data were analysed using independent component analysis to
      extract large-scale networks of task-related activations. RESULTS: Similar
      working memory networks were activated in all groups. However, in three out of
      nine networks related to the experimental task there was a graded response
      difference in fMRI signal amplitudes, where patients with schizophrenia showed
      greater activation than those with bipolar disorder, who in turn showed more
      activation than healthy controls. Secondary analysis of the patient groups showed
      that these activation patterns were associated with history of psychosis and
      current elevated mood in bipolar disorder. CONCLUSIONS: The same brain networks
      were related to working memory in schizophrenia, bipolar disorder and controls.
      However, some key networks showed a graded hyperactivation in the two patient
      groups, in line with a continuum of neuronal abnormalities across psychotic
      disorders.

PMID- 24434075
TI  - Epidemic of charcoal burning suicide in Japan.
AB  - BACKGROUND: The charcoal burning suicide epidemics in both Hong Kong and Taiwan
      have been well documented. However, little is known about the situation in Japan.
      AIMS: To examine the impact of charcoal burning suicide on the overall and other
      method-specific suicide rates between 1998 and 2007 in Japan. METHOD: Using data
      obtained from the Vital Statistics of Japan, negative binomial regression
      analyses were performed to investigate the impact of the charcoal burning method.
      RESULTS: In males and females aged 15-24 and 25-44 years, the charcoal burning
      epidemic led to a substantial increase in overall suicides, without a decrease in
      other methods. In all other age groups, no such trend was observed. CONCLUSIONS:
      In young Japanese, the charcoal burning method may have appealed to individuals
      who might not have chosen other highly or relatively lethal methods, and
      consequently led to an increase in overall suicides.

PMID- 24434076
TI  - Soluble complement complex C5b-9 promotes microglia activation.
AB  - Soluble C5b-9 has been described as a pro-inflammatory mediator that triggers
      cell activation rather than inducing cell death. Microglia is the most important
      immune cell involved in inflammatory response in the CNS. Although microglia
      activation induced by various stimuli has been well characterized, the role of
      C5b-9 in microglia has not been well studied. In the current experiment, we
      utilized assembled functional C5b-9 to treat microglia and analyzed the function.
      We found that soluble C5b-9 could promote microglia activation by up-regulation
      of costimulatory molecules and increase cytokine secretion. Our results suggested
      that soluble C5b-9 possessed immunoregulatory potential on microglia. 

PMID- 24434077
TI  - Therapeutic effect of anti-alphav integrin mAb on Theiler's murine
      encephalomyelitis virus-induced demyelinating disease.
AB  - We examined the regulatory role of alphav integrins in the development of
      Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV
      IDD), a model of multiple sclerosis (MS). Blockade of alphav integrins by anti
      alphav integrin monoclonal antibody (mAb) in the effector phase significantly
      suppressed the development of TMEV-IDD both clinically and histologically. The
      number of infiltrating mononuclear cells (MNCs) in the CNS was significantly
      decreased in mice treated with anti-alphav integrin mAb. Flow cytometric analysis
      of cytokine staining revealed that absolute numbers of IFN-gamma- and IL-17
      producing CD4+ and IFN-gamma-producing CD8+ T cells were significantly decreased
      in the CNS of mice treated with anti-alphav integrin mAb. These data suggest that
      alphav integrins may play important roles in the development of TMEV-IDD. 

PMID- 24434078
TI  - Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence.
AB  - PURPOSE: Mucosal melanoma is a rare but aggressive subtype of melanoma with
      unique clinicopathologic features. We hypothesize that mucosal melanoma shows
      predilection for separate and unique metastatic pathways. MATERIALS AND METHODS:
      This was a retrospective analysis of 19 patients (5 men and 14 women; median age
      60 years, range 38-76 years) with metastatic mucosal melanoma presenting to a
      tertiary oncology center between 2005 and 2010. We performed a review of medical
      records and histologic and imaging studies to evaluate the natural history,
      metastatic patterns and the role of imaging in the management of patients with
      advanced mucosal melanoma. RESULTS: At presentation, disease was confined to the
      primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most
      patients. The most common site of metastasis was the lungs (89%, n = 16),
      followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal
      melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to
      the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n =
      4). CONCLUSION: Pathways of metastatic spread in mucosal melanoma may differ from
      other forms of melanoma and between different primary sites of mucosal origin.

PMID- 24434079
TI  - Influence of pacing manipulation on performance of juniors in simulated 400-m
      swim competition.
AB  - PURPOSE: To date, there has been limited research examining the influence of
      pacing pattern (PP) on middle-distance swimming performance. As such, the purpose
      of the current study was to examine the influence of PP manipulation on 400-m
      freestyle swimming performance. METHODS: 15 front-crawl swimmers (5 female, 10
      male; age 18 +/- 2 y) performed 3 simulated 400-m swimming events. The initial
      trial was self-selected pacing (PPSS). The following 2 trials were performed in a
      counterbalanced order and required participants to complete the first 100 m more
      slowly (PPSLOW: 4.5% +/- 2.2%) or quickly (PPFAST: 2.4% +/- 1.6%) than the PPSS
      trial. 50-m split times were recorded during each trial. RESULTS: Overall
      performance time was faster in PPSS (275.0 +/- 15.9 s) than in PPFAST (278.5 +/-
      16.4 s, P = .05) but not significantly different from PPSLOW (277.5 +/- 16.2 s, P
      = .22). However, analysis for practical relevance revealed that pacing
      manipulation resulted in a "likely" (>88.2%) decrease in performance compared
      with PPSS. CONCLUSION: Moderate manipulation of the starting speed during
      simulated 400-m freestyle races seems to affect overall performance. The observed
      results indicate that PPSS is optimal in most individuals, yet it seems to fail
      in some swimmers. Future research should focus on the identification of athletes
      possibly profiting from manipulations.

PMID- 24434080
TI  - Liquid fructose downregulates Sirt1 expression and activity and impairs the
      oxidation of fatty acids in rat and human liver cells.
AB  - Fructose ingestion is associated with the production of hepatic steatosis and
      hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous
      induction of fatty acid synthesis and inhibition of fatty acid oxidation is
      required. We aimed to determine the mechanism involved in the inhibition of fatty
      acid oxidation by fructose and whether this effect occurs also in human liver
      cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7
      or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes
      were incubated with fructose 25mM for 24h. The expression and activity of the
      enzymes and transcription factors relating to fatty acid beta-oxidation were
      evaluated. Fructose inhibited the activity of fatty acid beta-oxidation only in
      livers of 14-day fructose-supplemented rats, as well as the expression and
      activity of peroxisome proliferator activated receptor alpha (PPARalpha). Similar
      results were observed in FaO and HepG2 cells and human hepatocytes. PPARalpha
      downregulation was not due to an osmotic effect or to an increase in protein
      phosphatase 2A activity caused by fructose. Rather, it was related to increased
      content in liver of inactive and acetylated peroxisome proliferator activated
      receptor gamma coactivator 1alpha, due to a reduction in sirtuin 1 expression and
      activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing
      PPARalpha expression and activity, both in rat and human liver cells, by a
      mechanism involving sirtuin 1 down-regulation.

PMID- 24434081
TI  - Color me healthy: food diversity in school community gardens in two rapidly
      urbanising Australian cities.
AB  - Community garden research has focused on social aspects of gardens, neglecting
      systematic analysis of what food is grown. Yet agrodiversity within community
      gardens may provide health benefits. Diverse fruit and vegetables provide
      nutritional benefits, including vitamins, minerals and phytochemicals. This paper
      reports research that investigated the agro-biodiversity of school-based
      community gardens in Brisbane and Gold Coast cities, Australia. Common
      motivations for establishing these gardens were education, health and
      environmental sustainability. The 23 gardens assessed contained 234 food plants,
      ranging from 7 to 132 plant types per garden. This included 142 fruits and
      vegetables. The nutritional diversity of fruits and vegetable plants was examined
      through a color classification system. All gardens grew fruits and vegetables
      from at least four food color groups, and 75% of the gardens grew plants from all
      seven color groups. As places with high agrodiversity, and related nutritional
      diversity, some school community gardens can provide children with exposure to a
      healthy range of fruit and vegetables, with potential flow-on health benefits. 

PMID- 24434082
TI  - Relationship between urban sprawl and physical activity, obesity, and morbidity -
      update and refinement.
AB  - AIMS: This study aims to model multiple health outcomes and behaviors in terms of
      the updated, refined, and validated county compactness/sprawl measures. METHODS:
      Multiple health outcomes and behaviors are modeled using multi-level analysis.
      RESULTS: After controlling for observed confounding influences, both original and
      new compactness measures are negatively related to BMI, obesity, heart disease,
      high blood pressure, and diabetes. Indices are not significantly related to
      physical activity, perhaps because physical activity is not defined broadly to
      include active travel to work, shopping, and other destinations. CONCLUSIONS:
      Developing urban and suburban areas in a more compact manner may have some
      salutary effect on obesity and chronic disease trends.

PMID- 24434083
TI  - More than just hormones: H295R cells as predictors of reproductive toxicity.
AB  - Many of the commonly observed reproductive toxicities associated with therapeutic
      compounds can be traced to a disruption of the steroidogenic pathway. We sought
      to develop an in vitro assay that would predict reproductive toxicity and be high
      throughput in nature. H295R cells, previously validated as having an intact and
      functional steroidogenic pathway, were treated with 83 known-positive and 79
      known-negative proprietary and public-domain compounds. The assay measured the
      expression of the key enzymes STAR, 3betaHSD2, CYP17A1, CYP11B2, CYP19A1,
      CYP21A2, and CYP11A1 and the hormones DHEA, progesterone, testosterone, and
      cortisol. We found that a Random Forest model yielded a receiver operating
      characteristic area under the curve (ROC AUC) of 0.845, with sensitivity of 0.724
      and specificity of 0.758 for predicting in vivo reproductive toxicity with this
      in vitro assay system. 

PMID- 24434084
TI  - Endoscopic removal of obstructing sutures using argon plasma coagulation.

PMID- 24434085
TI  - Routine colonoscopy after left-sided acute uncomplicated diverticulitis: a
      systematic review.

PMID- 24434087
TI  - A numerical flow analysis using the concept of inflow age for oxidation pond
      design.
AB  - A numerical flow analysis for the design of an oxidation pond was conducted to
      investigate the optimal flow characteristics. This analysis includes the inflow
      rate and the shape and depth of the oxidation pond. The total area and maximum
      depth of the pond were 500 m(2) and 3 m, respectively. We defined the retention
      time, retention time ratio, homogeneity index, and inflow exchange efficiency in
      order to choose the optimal conditions. The optimum width to length ratio and
      depth of the pond were found to be 1:5 and 2 m, respectively. 

PMID- 24434086
TI  - A novel subtyping assay for detection of Clostridium difficile virulence genes.
AB  - This proof-of-concept study demonstrates the application of a novel nucleic acid
      detection platform to detect Clostridium difficile in subjects presenting with
      acute diarrheal symptoms. This method amplifies three genes associated with C.
      difficile infection, including genes and deletions (cdtB and tcdC) associated
      with hypervirulence attributed to the NAP1/027/BI strain. Amplification of DNA
      from the tcdB, tcdC, and cdtB genes was performed using a droplet-based sandwich
      platform with quantitative real-time PCR in microliter droplets to detect and
      identify the amplified fragments of DNA. The device and identification system are
      simple in design and can be integrated as a point-of-care test to help rapidly
      detect and identify C. difficile strains that pose significant health threats in
      hospitals and other health-care communities. 

PMID- 24434088
TI  - Incidence of cardiovascular outcomes and diabetes mellitus among users of second
      generation antipsychotics.
AB  - OBJECTIVE: To examine the risk of cardiovascular outcomes and diabetes mellitus
      in patients prescribed second-generation antipsychotics. METHOD: From the
      MarketScan claims database, nondiabetic adults prescribed aripiprazole between
      July 2003 and March 2010 were propensity score-matched with patients prescribed
      olanzapine, quetiapine, risperidone, and ziprasidone. Patients were followed
      through the claims for International Classification of Diseases, Ninth Revision
      codes indicating myocardial infarction, stroke, heart failure, coronary
      bypass/angioplasty procedures, and incident diabetes. Incidence rates of each
      outcome were calculated and compared between aripiprazole and the other second
      generation antipsychotics using Cox models. RESULTS: Aripiprazole initiators were
      matched 1:1 to 9,917 olanzapine, 14,935 quetiapine, 10,192 risperidone, and 5,696
      ziprasidone initiators. Increased risk was found with olanzapine for stroke
      (hazard ratio = 1.43; 95% confidence interval, 1.05-1.95) and any cardiovascular
      event (1.28; 1.05-1.55); with quetiapine for stroke (1.58; 1.19-2.09), heart
      failure (1.55; 1.15-2.11), and any cardiovascular event (1.50; 1.25-1.79); and
      with risperidone for stroke (1.54; 1.12-2.12), heart failure (1.43; 1.02-1.99),
      and any cardiovascular event (1.49; 1.21-1.83). Ziprasidone showed no significant
      difference in risk from aripiprazole for any outcome. Incidence of diabetes
      ranged from 18 to 21 events per 1,000 person-years in each cohort and did not
      differ significantly between second-generation drugs. CONCLUSIONS: This analysis
      of real-world data found lower risk of some cardiovascular events with
      aripiprazole than with olanzapine, quetiapine, or risperidone, but no differences
      were found with ziprasidone. There were no significant differences in risk of
      diabetes. Limitations include use of claims data and inability to adequately
      control for differential prescribing of second-generation antipsychotics to
      patients at higher risk of diabetes.

PMID- 24434089
TI  - Gender-specific suicide risk factors: a case-control study of individuals with
      major depressive disorder.
AB  - OBJECTIVE: Available information on risk for suicide completion in females is
      limited and often extrapolated from studies conducted in males. However, the
      validity of extending to females risk factors identified among male suicide cases
      is unclear. In this study, we aimed to investigate clinical and behavioral risk
      factors for suicide among female depressed patients and compare them to similar
      factors among male depressed patients. METHOD: We identified 201 suicide
      completers (160 male and 41 female) who died during an episode of major
      depressive disorder (MDD). Cases were compared to 127 living patients with MDD
      (88 male and 39 female). All subjects were characterized for Axis I and II
      diagnoses using the Structured Clinical Interview for DSM-IV Axis I Disorders and
      Structured Clinical Interview for DSM-IV Axis II Personality Disorders according
      to the DSM-IV, as well as behavioral and temperament dimensions using proxy-based
      interviews. The primary outcome was measures of impulsive and impulsive
      aggressive behaviors. RESULTS: Compared to controls, male, but not female suicide
      cases had higher levels of impulsive aggression (P < .05). Nonimpulsive
      aggression differentiated both female (P < .05) and male (P < .01) suicide cases
      from controls. However, nonimpulsive aggression and impulsive aggression were
      correlated constructs in males (r = 0.297; P < .001), yet uncorrelated among
      females (r = 0.121; P = .390). Established risk factors for suicide, such as
      alcohol and substance dependence, cluster B disorders, and elevated hostility and
      aggression, were replicated in the pooled-sex analyses, and, though not
      statistically significant in discriminating between suicide cases and controls by
      gender, maintained strong group differences. CONCLUSIONS: Males and females share
      many risk factors for suicide in MDD, yet alcohol dependence is much more
      specific though less sensitive among depressed females. Nonimpulsive aggression
      is part of a diathesis for suicide in females, which is distinct from the well
      characterized impulsive aggression that is consistently reported in a portion of
      male suicide cases.

PMID- 24434090
TI  - Atomoxetine tolerability in pediatric and adult patients receiving different
      dosing strategies.
AB  - OBJECTIVE: Examine how different dosing schedules and recent stimulant therapy
      effect incidence, time to onset, and duration of common treatment-emergent
      adverse events (TEAEs) during atomoxetine treatment. METHOD: Post hoc analyses
      including safety data (open-ended questions) from 22 pediatric and 3 adult
      atomoxetine trials (1998-2009) in patients with attention-deficit/hyperactivity
      disorder. Most common TEAEs were determined by incidence rates and frequency of
      consumer and clinician inquiries. Onset and duration of TEAEs with slow versus
      fast titration, once-daily versus twice-daily dosing, and previous stimulant
      exposure were compared among treatment groups using Kaplan-Meier methods.
      RESULTS: In pediatric patients, the most commonly reported TEAEs were abdominal
      pain, decreased appetite, fatigue, nausea, somnolence, and vomiting; time to
      onset of TEAEs was significantly shorter for once-daily versus twice-daily dosing
      for all TEAEs (P <= .007) and for fast versus slow titration for abdominal pain,
      decreased appetite, and somnolence (all P values <= .009); duration of TEAEs with
      once-daily dosing was significantly longer for decreased appetite (P = .001) and
      nausea (P = .041); and more common in stimulant-naive patients versus patients
      with prior stimulant use were abdominal pain, decreased appetite, and fatigue (P
      <= .047). In adult patients, the most commonly reported TEAEs (erectile
      dysfunction data were excluded) were nausea, insomnia, decreased appetite,
      urinary hesitation/urinary retention, and fatigue; insomnia had a significantly
      shorter time to onset and longer duration with twice-daily versus once-daily
      dosing (P <= .032) and fast versus slow titration (P <= .007). CONCLUSIONS: Time
      to onset and resolution of TEAEs appear dependent on dosing schedule and
      titration speed. These findings can help to better manage tolerability issues and
      set appropriate expectations for clinicians and patients during atomoxetine
      titration, potentially improving treatment adherence and success.

PMID- 24434091
TI  - The retinoid X receptor agonist bexarotene relieves positive symptoms of
      schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter
      trial.
AB  - OBJECTIVE: The limitations of antipsychotic therapy in schizophrenia and
      schizoaffective disorder led to the investigation of the putative utility of
      pharmacologic augmentation strategies. The antitumor agent bexarotene via nuclear
      retinoid X receptor (RXR) activation might modulate numerous metabolic pathways
      involved in the pathogenesis of schizophrenia and schizoaffective disorder. This
      trial aimed to investigate efficacy and safety of add-on bexarotene to ongoing
      antipsychotic treatment of patients with schizophrenia or schizoaffective
      disorder. METHOD: Ninety inpatients and outpatients that met DSM-IV-TR criteria
      for schizophrenia or schizoaffective disorder participated in a 6-week, double
      blind, randomized, placebo-controlled multicenter study. Bexarotene (75 mg/d) was
      added to ongoing antipsychotic treatment from October 2008 to December 2010. The
      reduction in the severity of symptoms on the Positive and Negative Syndrome Scale
      (PANSS) was a primary outcome. Secondary outcomes included general functioning,
      quality of life, and side effect scales. RESULTS: Seventy-nine participants (88%)
      completed the protocol. Controlling for antipsychotic agents, a mixed model
      showed that patients who received adjunctive bexarotene had significantly lower
      PANSS positive scale scores compared to patients who received placebo (F = 8.6, P
      = .003; treatment arms * time, F = 2.7, P = .049), with moderate effect size (d =
      0.48; 95% CI,0.04-0.93). Patients with mean or higher baseline PANSS positive
      scale scores and patients who did not take lipid-reducing agents revealed greater
      amelioration of positive symptoms (F = 7.4, P = .008). Other symptoms and
      secondary outcome measures were not affected by adjunctive bexarotene. Bexarotene
      was well tolerated, though 2 reversible side effects were reported: a significant
      increase in total cholesterol levels (P < .001) and a decrease in total thyroxine
      levels (P < .001). CONCLUSIONS: Bexarotene might potentially be a novel adjuvant
      therapeutic strategy for schizophrenia, particularly for the reduction of
      positive symptoms. The potential benefits and risks of ongoing administration of
      bexarotene warrant further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00535574.

PMID- 24434092
TI  - Depressive and anxiety disorders predicting first incidence of alcohol use
      disorders: results of the Netherlands Study of Depression and Anxiety (NESDA).
AB  - INTRODUCTION: Depressive and anxiety disorders may predict first incidence of
      alcohol abuse and alcohol dependence. This study aims to identify those persons
      who are at an increased risk of developing alcohols abuse or alcohol dependence
      by considering the heterogeneity of depressive and anxiety disorders and
      exploring the role of other risk factors. METHOD: In a large sample of persons
      with and without baseline DSM-IV depressive or anxiety disorders (n = 2,676; 18
      65 years; assessed in 2004-2007), the first incidences of DSM-IV alcohol abuse
      and alcohol dependence during a 4-year follow-up were considered as primary
      outcomes. Status (remitted or current disorder), severity, and type (specific
      disorders) of depressive and anxiety disorders were assessed, as well as other
      risk factors, such as sociodemographic, vulnerability, and addiction-related
      factors. RESULTS: Cumulative first-incidence rates of alcohol abuse and alcohol
      dependence were 2.0% and 3.0%, respectively. Persons with current, but not
      remitted, depressive or anxiety disorders were at an increased risk of a first
      incidence of alcohol dependence (hazard ratio [HR] = 2.69; 95% CI, 1.37-5.29),
      but not first incidence of alcohol abuse (HR = 0.55; 95% CI, 0.28-1.09). Although
      this association was not conditional on the type of disorder, first-incidence
      rates of alcohol dependence gradually increased with the number of depressive and
      anxiety disorders (HR per SD increase = 1.65; 95% CI, 1.37-2.00). Subthreshold
      alcohol problems especially (P < .001), but also recent negative life events (P =
      .06), were additional independent predictors of first incidence of alcohol
      dependence. CONCLUSION: Current depressive disorder, anxiety disorder, or both
      significantly predicted first incidence of alcohol dependence, which stresses the
      importance of addiction prevention strategies for depressed and anxious patients
      in mental health settings. Subthreshold alcohol problems and recent negative life
      events may help to identify persons at an increased risk for developing alcohol
      dependence.

PMID- 24434093
TI  - Do benzodiazepines reduce the effectiveness of exposure therapy for posttraumatic
      stress disorder?
AB  - OBJECTIVE: Benzodiazepines, other anxiolytics, or sedative hypnotics are
      prescribed for 30%-50% of posttraumatic stress disorder (PTSD) patients. Prior
      data and theory suggest that these medications may inhibit response to exposure
      therapy, one of the most effective PTSD treatments. The present post hoc study
      reanalyzed results from a psychotherapy trial to assess whether benzodiazepine
      use was associated with reduced response to exposure therapy. METHOD: Between
      August 2002 and October 2005, 283 female veterans and soldiers meeting DSM-IV
      criteria for PTSD were randomly assigned to 10 weekly 90-minute sessions of
      either prolonged exposure (n = 140) or present-centered psychotherapy (n = 143).
      Benzodiazepine use (n = 57) or non-use (n = 226) at intake was not randomly
      assigned. Multilevel modeling was used to assess the effects of benzodiazepine
      status, psychotherapy condition, and their interaction on changes on the
      Clinician-Administered PTSD Scale and the PTSD Checklist during the treatment and
      6-month follow-up periods. RESULTS: Consistent with prior reports from these
      data, prolonged exposure psychotherapy produced greater reductions per week in
      PTSD symptoms than did present-centered psychotherapy (b = -0.48, P = .02).
      Patients prescribed benzodiazepines did not have weaker response to prolonged
      exposure, but demonstrated poorer posttreatment maintenance of gains from present
      centered psychotherapy (b = -0.78, P < .001). CONCLUSIONS: Prolonged exposure is
      a sufficiently robust treatment that patients who are taking benzodiazepines can
      benefit from it. It is unclear whether benzodiazepine use or other patient
      factors accounted for benzodiazepine recipients' poorer maintenance of gains in
      present-centered psychotherapy. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00032617.

PMID- 24434094
TI  - Prospective trial of customized adherence enhancement plus long-acting injectable
      antipsychotic medication in homeless or recently homeless individuals with
      schizophrenia or schizoaffective disorder.
AB  - BACKGROUND: Treatment nonadherence in people with schizophrenia is associated
      with relapse and homelessness. Building on the usefulness of long-acting
      medication and our work in psychosocial interventions to enhance adherence, we
      conducted a prospective uncontrolled trial of customized adherence enhancement
      (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate
      in 30 homeless or recently homeless individuals with DSM-IV-defined schizophrenia
      or schizoaffective disorder. METHOD: Participants received monthly CAE and LAI
      (CAE-L) for 6 months. Primary outcomes were adherence, as measured by the Tablets
      Routine Questionnaire, and housing status. Secondary outcomes included
      psychiatric symptoms, functioning, side effects, and hospitalizations. The study
      was conducted from July 2010 to December 2012. RESULTS: The mean age of
      participants was 41.8 years (SD = 8.6); they were mainly minorities (90%, n = 27
      African-American) and mainly single/never married (70%, n = 21). Most (97%, n =
      29) had past or current substance abuse and had been incarcerated (97%, n = 29).
      Ten individuals (33%) terminated the study prematurely. CAE-L was associated with
      good adherence to LAI (at 6 months, 76%) and dramatic improvement in oral
      medication adherence, which changed from missing 46% of medication at study
      enrollment to missing only 10% at study end (P = .03). There were significant
      improvements in psychiatric symptoms (P < .001) and functioning (P < .001).
      Akathisia was a major side effect with LAI. CONCLUSIONS: While interpretation of
      findings must be tempered by the methodological limitations, CAE-L appears to be
      associated with improved adherence, symptoms, and functioning in homeless or
      recently homeless individuals with schizophrenia or schizoaffective disorder.
      Additional research is needed on effective and practical approaches to improving
      health outcomes for homeless people with serious mental illness. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT01152697.

PMID- 24434096
TI  - Depression and risk of dementia: exploring the interface.

PMID- 24434095
TI  - Depressive symptoms in healthy apolipoprotein E epsilon4 carriers and
      noncarriers: a longitudinal study.
AB  - OBJECTIVE: To determine if symptoms of depression accelerate in cognitively
      normal apolipoprotein E (APOE) epsilon4 carriers as compared to noncarriers.
      METHOD: Six hundred thirty-three cognitively and functionally normal members of
      the Arizona APOE Cohort aged 21-86 years underwent neuropsychological testing
      every 1 to 2 years that included the Hamilton Depression Rating Scale, the Beck
      Depression Inventory, the Geriatric Depression Scale, and the Personality
      Assessment Inventory. We estimated the longitudinal change on these measures
      using mixed models that simultaneously modeled cross-sectional and longitudinal
      effects of age on depression scores by APOE status and the interaction between
      the two. We also estimated incident depression on the basis of accepted clinical
      cut-scores on depression measures and use of depression medications. RESULTS: The
      mean length of follow-up was 7.7 years. Comparing APOE epsilon4 carriers with
      noncarriers revealed no significant longitudinal difference in the rate of change
      or slope of change on any depression scale or subscale. There was also no
      difference in incident depression or antidepressant drug use between the carrier
      and noncarrier groups. CONCLUSIONS: These data fail to support a relationship
      between APOE genotype and longitudinal change in depression symptoms, suggesting
      that depression symptoms may not be intrinsic to the early preclinical phase of
      Alzheimer's disease.

PMID- 24434097
TI  - Predictors of suicide attempt in early-onset psychosis: methodological issues and
      concerns.

PMID- 24434098
TI  - Drs Sanchez-Gistau and Castro-Fornieles reply.

PMID- 24434099
TI  - The association of disaster-related experiences and self-reported recollections
      of national trauma with posttraumatic stress disorder symptoms following
      Hurricane Sandy.

PMID- 24434100
TI  - Augmenting selective serotonin reuptake inhibitors with clomipramine in obsessive
      compulsive disorder: benefits and risks.
AB  - A small body of literature suggests that clomipramine may usefully augment
      selective serotonin reuptake inhibitor (SSRI) treatment in obsessive-compulsive
      disorder (OCD) patients who do not respond to SSRI monotherapy. The combination,
      however, is associated with the risk of clinically significant drug interactions.
      Clomipramine can raise the blood levels and hence the adverse effects of most
      SSRIs, and many SSRIs can raise the blood levels and hence the adverse effects of
      clomipramine. The latter situation is more important because certain dose
      dependent adverse effects of clomipramine, such as seizures, can be life
      threatening. This article presents an evidence-based discussion of the
      pharmacodynamic and pharmacokinetic adverse effects of the SSRI-clomipramine
      combination along with suggestions for dosing and monitoring when the combination
      is used in OCD. 

PMID- 24434101
TI  - The perfusion pattern in a patient with lithium intoxication mimicking
      Creutzfeldt-Jakob disease.

PMID- 24434102
TI  - Prophylactic antipsychotic use for postoperative delirium: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: Although antipsychotics have been used empirically to prevent the
      development of postoperative delirium, there has been no confirming evidence to
      support their use. Thus, we conducted a systematic review and a meta-analysis to
      elucidate their efficacy and tolerability in surgical patients. DATA SOURCES:
      MEDLINE, EMBASE, the Cochrane Library databases, CINAHL, and PsycINFO were
      searched up to February 2013 without language restrictions, using the following
      keywords: (antipsychotics OR [nonproprietary name of each antipsychotic
      medication, separated by OR]) AND delirium AND (randomized OR random OR
      randomly). STUDY SELECTION: Randomized controlled trials comparing prophylactic
      use of antipsychotics with placebo in surgical patients were included. DATA
      EXTRACTION: Two authors extracted and scrutinized the data. The risk ratio (RR),
      95% confidence interval (CI), number needed to treat (NNT), and standardized mean
      difference were used. RESULTS: Six studies (3 haloperidol, 1 olanzapine, and 2
      risperidone) including 1,689 surgical patients were identified. The results
      showed significant efficacy in reducing the occurrence of delirium (RR = 0.50,
      95% CI = 0.34 to 0.73, P = .0003; NNT = 7, P = .001, 6 studies). Sensitivity
      analysis showed that second-generation antipsychotics were superior to placebo
      (RR = 0.36, P < .00001; NNT = 4, P < .00001), whereas haloperidol failed to show
      superiority to placebo. There were no statistically significant differences
      between groups in severity of delirium, discontinuation rate, or rates of several
      adverse events. CONCLUSIONS: Our results suggest that second-generation
      antipsychotics are more beneficial than placebo for preventing the incidence of
      delirium. Among patients who do develop delirium, the severity of delirium is not
      reduced in those who received prophylactic antipsychotics.

PMID- 24434103
TI  - Psychoeducational interventions for family members of people with schizophrenia:
      a mixed-method systematic review.
AB  - OBJECTIVE: This systematic review investigates the effectiveness of
      psychoeducation in improving the well-being of family members of people with
      schizophrenia and identifies the common ingredients, implementation
      considerations, and participants' feedback. DATA SOURCES: Published articles in
      either English or Chinese which reported psychoeducational intervention studies
      that targeted family members of people with schizophrenia as participants, were
      searched with the keywords schizophrenia and/or psychosis and
      psychoeducation/psychoeducational interventions in 8 databases (MEDLINE,
      PsycINFO, CINAHL, EMBASE, Web of Science, Applied Social Sciences Index and
      Abstracts [ASSIA], Cochrane Reviews Library, and CENTRAL), from the time of
      inception of the various databases to March 2012. STUDY SELECTION: Fifty-eight
      articles reporting 44 research studies met all the inclusion criteria and the
      quality assessment requirement and were included in the review. DATA EXTRACTION:
      Data from trials, quantitative studies, and qualitative research were extracted
      to address 3 parallel syntheses, following the Evidence for Policy and Practice
      Information Coordination Centre mixed-method systematic approach. RESULTS:
      Psychoeducation was found to be consistently effective in improving family
      members' knowledge and coping. However, it was less successful in changing family
      members' psychological morbidities, burden, or expressed emotion. Common
      ingredients across interventions included coverage of common coping strategies
      and problem-solving strategies to enhance communication or coping. Particularly
      valued by family carers were a group format to share experiences with other
      carers, skillful facilitation by professionals, and knowledge and skill
      development. CONCLUSIONS: This review indicates that psychoeducation should be
      routinely provided to family members as early as possible following contact with
      health services. Suggestions are made for optimal psychoeducational intervention
      design and its successful implementation, and for further research to establish
      the enhanced effect of booster sessions, between-session practice, and online
      delivery.

PMID- 24434104
TI  - Long-term trajectories of posttraumatic stress disorder in veterans: the role of
      social resources.
AB  - OBJECTIVE: To (1) identify long-term trajectories of combat-induced posttraumatic
      stress disorder (PTSD) symptoms over a 20-year period from 1983 to 2002 in
      veterans with and without combat stress reaction (CSR) and (2) identify social
      predictors of these trajectories. METHOD: A latent growth mixture modeling
      analysis on PTSD symptoms was conducted to identify PTSD trajectories and
      predictors. PTSD was defined according to DSM-III and assessed through the PTSD
      Inventory. Israeli male veterans with (n = 369) and without (n = 306) CSR were
      queried at 1, 2, and 20 years after war about combat exposure, military unit
      support, family environment, and social reintegration. RESULTS: For both study
      groups, we identified 4 distinct trajectories with varying prevalence across
      groups: resilience (CSR = 34.4%, non-CSR = 76.5%), recovery (CSR = 36.3%, non-CSR
      = 10.5%), delayed onset (CSR = 8.4%, non-CSR = 6.9%), and chronicity (CSR =
      20.9%, non-CSR = 6.2%). Predictors of trajectories in both groups included
      perception of war threat (ORs = 1.59-2.47, P values <= .30), and negative social
      reintegration (ORs = 0.24-0.51, P values <= .047). Social support was associated
      with symptomatology only in the CSR group (ORs = 0.40-0.61, P values <= .045),
      while family coherence was predictive of symptomatology in the non-CSR group (OR
      = 0.76, P = .015) but not in the CSR group. CONCLUSIONS: Findings confirmed
      heterogeneity of long-term sequelae of combat, revealing 4 trajectories of
      resilience, recovery, delay, and chronicity in veterans with and without CSR.
      Symptomatic trajectories were more prevalent for the CSR group, suggesting that
      acute functional impairment predicts pathological outcomes. Predictors of
      symptomatic trajectories included perceived threat and social resources at the
      family, network, and societal levels.

PMID- 24434105
TI  - Antipsychotics for cocaine or psychostimulant dependence: systematic review and
      meta-analysis of randomized, placebo-controlled trials.
AB  - OBJECTIVE: Since cocaine and psychostimulant dependence are related to increased
      dopamine release, antipsychotics have been tried to reduce their reinforcing
      properties. A meta-analysis was undertaken to assess the efficacy and
      tolerability of antipsychotics in cocaine- or stimulant-dependent patients. DATA
      SOURCES: We searched PubMed, Cochrane Library databases, and PsycINFO from
      database inception until June 24, 2013, using the following keywords: (randomized
      OR random OR randomly) AND (placebo) AND (methylphenidate OR cocaine OR
      methamphetamine OR amphetamine OR 3,4-methylenedioxymethamphetamine) AND
      (dependence OR abuse) AND (antipsychotic OR neuroleptic OR 34 specific
      antipsychotic names). STUDY SELECTION: Included were randomized, placebo
      controlled trials of antipsychotics lasting at least 2 weeks in patients with
      primary cocaine or psychostimulant dependence. Of 363 hits, we removed 316
      duplicates, 20 references based on abstract/title, and 13 ineligible full-text
      articles, retaining 14 trials for this meta-analysis. DATA EXTRACTION: Two
      authors independently extracted the data. Coprimary outcomes included degree of
      substance use and lack of abstinence. Risk ratio (RR), 95% CI, and standardized
      mean difference were calculated. RESULTS: Ten studies in patients with primary
      cocaine dependence (risperidone = 5, olanzapine = 3, reserpine = 2; n = 562) and
      4 in those with amphetamine/methamphetamine dependence (aripiprazole = 4; n =
      179) were meta-analyzed (14 studies, total n = 741). When study results were
      pooled together, antipsychotics did not differ from placebo in regard to cocaine
      use days and lack of cocaine or amphetamine/methamphetamine abstinence, severity
      of addiction, cocaine or amphetamine/methamphetamine craving, Clinical Global
      Impressions-Severity of Illness (CGI-S) scores, depression, anxiety, compliance,
      all-cause discontinuation, and several side effects. However, antipsychotics
      caused more intolerability-related discontinuation than placebo (P = .0009).
      Individually, aripiprazole was superior to placebo in regard to CGI-S (P = .001),
      while olanzapine was inferior to placebo in regard to cocaine craving (P = .03)
      and risperidone was inferior to placebo in regard to depression (P = .002).
      CONCLUSIONS: Antipsychotics had no advantages over placebo in regard to cocaine
      use and cocaine or psychostimulant abstinence or craving, while causing more
      intolerability-related discontinuations.

PMID- 24434106
TI  - Reduction of alcohol consumption and subsequent mortality in alcohol use
      disorders: systematic review and meta-analyses.
AB  - OBJECTIVE: To determine whether a reduction in drinking in individuals with
      alcohol use disorders resulted in reduced mortality risk. DATA SOURCES:
      Electronic searches were performed of MEDLINE, EMBASE, and ISI Web of Science and
      references of identified articles were searched up to May 2012 using these
      keywords: (alcohol dependence OR alcohol abuse) AND (mortality) AND (cohort OR
      follow-up). Only English-language articles were included. STUDY SELECTION:
      Sixteen cohort studies were identified that reported all-cause mortality risk by
      drinking groups measuring change in alcohol intake among people with alcohol use
      disorders. DATA EXTRACTION: Numbers of participants and deaths in each group;
      odds ratios (ORs); and demographic, clinical, and methodological variables were
      extracted. RESULTS: In comparison to continued heavy drinking, a reduction below
      heavy levels of alcohol use (including abstention) was associated with a
      substantially reduced risk of mortality (random-effects pooled OR = 0.41; 95% CI,
      0.34-0.50; P < .001). The OR was 0.35 (95% CI, 0.20-0.60; P < .001) for those who
      reached abstention and 0.61 (95% CI, 0.39-0.94; P = .026) for those who did not
      reach abstention but substantially reduced their consumption. The pooled OR for
      abstention compared to reduced consumption was 0.42 (95% CI, 0.19-0.92; P =
      .031). Meta-regression models did not reveal significant influences of study
      characteristics examined. CONCLUSIONS: Reduction of drinking in alcohol use
      disorders was associated with a marked reduction in mortality risk for those who
      reached abstinence or reduced drinking compared to continued heavy drinkers.
      Those who reached abstention showed the smallest mortality risk, lower than the
      risk for reduced consumption without abstinence.

PMID- 24434107
TI  - Changes in inpatient and postdischarge suicide rates in a nationwide cohort of
      Danish psychiatric inpatients, 1998-2005.
AB  - BACKGROUND: A reduction in the number of inpatient beds as well as shorter
      admissions have aroused concern that tendencies to deinstitutionalize may
      increase the suicide rate for psychiatric patients who have been hospitalized.
      One study indicates that a decreasing inpatient suicide rate may actually reflect
      a transfer to an increasing postdischarge suicide rate; however, uncertainties
      exist about this transfer, since it is not well studied. The objectives of this
      study were to estimate adjusted changes over time in suicide rates among
      psychiatric inpatients and recently discharged psychiatric patients and to
      estimate changes in these rates by gender and diagnosis. METHOD: Data on all
      psychiatric patients admitted from 1998 through 2005 in Denmark were extracted
      from the Danish Psychiatric Central Register and merged with information from the
      Danish Cause of Death Register. Calendar year was applied as an independent
      continuous variable in Cox survival analyses modeling the hazard of suicide
      during inpatient treatment and during the 3-month postdischarge period. Analyses
      were adjusted for sex, age, educational status, primary diagnosis, and previous
      suicide attempt. RESULTS: The overall inpatient suicide rate declined in
      psychiatric patients admitted from 1998 through 2005 (hazard ratio [HR] = 0.93
      [95% CI, 0.88-0.99]), particularly among women (HR = 0.87 [95% CI, 0.79-0.96]).
      The overall rate of suicide in the 3-month postdischarge period also declined
      significantly (HR = 0.94 [95% CI, 0.91-0.98]), which was explained mostly by a
      falling rate among men (HR = 0.94 [95% CI, 0.90-0.98]) as well as among patients
      who were discharged with a diagnosis of schizophrenia (HR = 0.90 [95% CI, 0.83
      0.99]). CONCLUSIONS: Although our results show a decreasing trend in suicide
      rates, the sizes of the rates emphasize that focus on suicide in mental health
      care settings must continue and be improved, as the rates are still very high.

PMID- 24434108
TI  - Assessing and managing pain and major depression with medical comorbidities.
AB  - Chronic pain is the leading reason patients see their primary care physician, and
      the burden of pain and depression in those with medical illness is particularly
      severe. Improving depressive symptoms can decrease physical symptoms in many
      patients, but these patients may require a different treatment strategy than
      those with depression alone. This activity provides guidance on recognizing and
      accurately diagnosing pain and major depression, managing these conditions using
      assessment tools and measurement-based care, avoiding unwanted side effects and
      drug interactions, and properly matching patients to appropriate treatments. 

PMID- 24434109
TI  - Working together to address domestic violence among veterans.
AB  - Most veterans do not have psychiatric illness and do not have problems with
      domestic violence, but PTSD is a strong risk factor for intimate partner
      violence. Other risk factors include depression and substance use disorders, and
      the risk is compounded by the presence of several factors. Clinicians should
      screen for domestic violence among veterans and their partners using direct,
      nonjudgmental questions. To improve their relationships, veterans may need help
      with problems such as mistrust, low esteem for self or others, and power/control
      conflicts. Veterans and their intimate partners should also receive education
      about any psychiatric diagnosis that is given, the problem of survival-mode
      thinking at home, and available resources such as cognitive-behavioral
      interventions to prevent or stop domestic violence. When addressing a veteran's
      domestic violence, coordination of care is necessary to reduce recidivism. With
      intimate partners, clinicians should discuss the support system and safety plan. 

PMID- 24434110
TI  - Strategies for achieving full remission when first-line antidepressants are not
      enough.
AB  - Remission rates for patients with major depressive disorder are discouragingly
      low. Even when first-line treatment is administered at an adequate dose for a
      sufficient duration, approximately two-thirds of patients will fail to achieve
      remission, and many who remit have residual symptoms. Clinicians must assess
      problems with the first treatment and select the most appropriate second-line
      treatment based on patient preference, clinical judgment, and any comorbid
      conditions. Strategies like implementing psychotherapy, switching agents, or
      augmenting antidepressants may help patients achieve remission. Patients may also
      require adjunctive therapy to target common residual symptoms such as fatigue or
      insomnia. 

PMID- 24434112
TI  - Value of cone-beam computed tomography in the process of diagnosis and management
      of disorders of the temporomandibular joint.
AB  - The objective of this study was to assess the value of cone-beam computed
      tomographic (CT) images in the primary diagnosis and management of 128
      outpatients with disorders of the temporomandibular joint (TMJ). Before a
      diagnosis was made and treatment planned, the history was taken, physical
      examination made, and the orthopantomogram studied. After assessment of the cone
      beam CT, the oral and maxillofacial surgeon (specialist or resident) was allowed
      to revise the provisional primary diagnosis and management. The degree of
      certainty was rated by the clinician before and after the cone-beam CT had been
      assessed. The primary diagnosis was changed in 32 patients (25%), additional
      diagnostic procedures were changed in 57 (45%), and the treatment was changed in
      15 (12%) (in 4 the treatment was changed to a (minimally) invasive procedure). A
      total of 74 patients (58%) had their diagnosis and management changed after the
      cone-beam CT had been assessed. Changes in diagnosis and management were
      clinically relevant in 9/32 and 9/61 patients, respectively. The clinician's
      certainty about the primary diagnosis increased after the cone-beam CT had been
      assessed in 57 patients. Logistic regression analysis showed that the odds in
      favour of changes in primary diagnosis and management increased when limited
      mandibular function was a primary symptom, the patient was taking medication for
      pain, and the articular eminence could not be assessed on OPT. Assessment of cone
      beam CT led to changes in primary diagnosis and management in more than half the
      patients with disorders of the TMJ. 

PMID- 24434113
TI  - Novel rhodamine derivate as high selective detection lead sensor.
AB  - A novel rhodamine based sensor 1 has been synthesized and characterized by NMR,
      FT-IR and mass. The binding properties of sensor 1 were investigated in the
      presence of various metal ions by UV-Vis spectroscopy and fluorescence
      spectroscopy. Sensor 1 showed colorimetric and high emission intensity
      enhancement in the presence of Pb(2+) in chloroform-THF (7:3). 

PMID- 24434115
TI  - Probabilistic approaches to compute uncertainty intervals and sensitivity factors
      of ultrasonic simulations of a weld inspection.
AB  - For comprehension purpose, numerical computations are more and more used to
      simulate the propagation phenomena observed during experimental inspections.
      However, the good agreement between experimental and simulated data necessitates
      the use of accurate input data and thus a good characterization of the inspected
      material. Generally the input data are provided by experimental measurements and
      are consequently tainted with uncertainties. Thus, it becomes necessary to
      evaluate the impact of these uncertainties on the outputs of the numerical model.
      The aim of this study is to perform a probabilistic analysis of an ultrasonic
      inspection of an austenitic weld containing a manufactured defect based on
      advanced techniques such as polynomial chaos expansions and computation of
      sensitivity factors (Sobol, DGSM). The simulation of this configuration with the
      finite element code ATHENA2D was performed 6000times with variations of the input
      parameters (the columnar grain orientation and the elastic constants of the
      material). The 6000 sets of input parameters were obtained from adapted
      statistical laws. The output parameters (the amplitude and the position of the
      defect echo) distributions were then analyzed and the 95% confidence intervals
      were determined. 

PMID- 24434114
TI  - Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B
      inhibitors: scaffold hopping from known antibacterial leads.
AB  - DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that
      ensures the regulation of DNA topology and has been genetically demonstrated to
      be a bactericidal drug target. We present the discovery and optimisation of a
      novel series of mycobacterial DNA gyrase inhibitors with a high degree of
      specificity towards the mycobacterial ATPase domain. Compound 5-fluoro-1-(2-(4-(4
      (trifluoromethyl)benzylamino)piperidin-1-yl)ethyl)indoline-2,3-dione (17) emerged
      as the most potent lead, exhibiting inhibition of MTB DNA gyrase supercoiling
      assay with an IC50 (50% inhibitory concentration) of 3.6 +/- 0.16 MUM, a
      Mycobacterium smegmatis GyrB IC50 of 10.6 +/- 0.6 MUM, and MTB minimum inhibitory
      concentrations of 6.95 MUM and 10 MUM against drug-sensitive (MTB H37Rv) and
      extensively drug-resistant strains, respectively. Furthermore, the compounds did
      not show any signs of cardiotoxicity in zebrafish ether-a-go-go-related gene
      (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic
      N-linked aminopiperidine analogues.

PMID- 24434116
TI  - Ultrasound-assisted handling force reduction during the solar silicon wafers
      production.
AB  - Surface adhesion between wet wafers poses great challenges for silicon wafer
      handling. It has been shown that both the shear and normal handling forces of the
      solar silicon wafers can be dramatically reduced by using the ultrasound energy.
      Approximately 20 and 5 times reduction in horizontal and vertical forces were
      achieved by as low power as 10W, and a good agreement was found between the
      measured values and the predictions of a simple model for the effect of
      longitudinal vibration we developed. 

PMID- 24434117
TI  - Effects of creatine monohydrate supplementation on simulated soccer performance.
AB  - PURPOSE: To determine the effects of acute short-term creatine (Cr)
      supplementation on physical performance during a 90-min soccer-specific
      performance test. METHODS: A double-blind, placebo-controlled experimental design
      was adopted during which 16 male amateur soccer players were required to consume
      20 g/d Cr for 7 d or a placebo. A Ball-Sport Endurance and Speed Test (BEAST)
      comprising measures of aerobic (circuit time), speed (12- and 20-m sprint), and
      explosive-power (vertical jump) abilities performed over 90 min was performed
      presupplementation and postsupplementation. RESULTS: Performance measures during
      the BEAST deteriorated during the second half relative to the first for both Cr
      (1.2-2.3%) and placebo (1.0-2.2%) groups, indicating a fatigue effect associated
      with the BEAST. However, no significant differences existed between groups,
      suggesting that Cr had no performance-enhancing effect or ability to offset
      fatigue. When effect sizes were considered, some measures (12-m sprint, -0.53 +/-
      0.69; 20-m sprint, -0.39 +/- 0.59) showed a negative tendency, indicating chances
      of harm were greater than chances of benefit. CONCLUSIONS: Acute short-term Cr
      supplementation has no beneficial effect on physical measures obtained during a
      90-min soccer-simulation test, thus bringing into question its potential as an
      effective ergogenic aid for soccer players.

PMID- 24434118
TI  - Species-specific relative AHR1 binding affinities of 2,3,4,7,8
      pentachlorodibenzofuran explain avian species differences in its relative
      potency.
AB  - Results of recent studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PeCDF)
      and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are equipotent in domestic chicken
      (Gallus gallus domesticus) while PeCDF is more potent than TCDD in ring-necked
      pheasant (Phasianus colchicus) and Japanese quail (Coturnix japonica). To
      elucidate the mechanism(s) underlying these differences in relative potency of
      PeCDF among avian species, we tested the hypothesis that this is due to species
      specific differential binding affinity of PeCDF to the aryl hydrocarbon receptor
      1 (AHR1). Here, we modified a cell-based binding assay that allowed us to measure
      the binding affinity of dioxin-like compounds (DLCs) to avian AHR1 expressed in
      COS-7 (fibroblast-like cells). The results of the binding assay show that PeCDF
      and TCDD bind with equal affinity to chicken AHR1, but PeCDF binds with greater
      affinity than TCDD to pheasant (3-fold) and Japanese quail (5-fold) AHR1. The
      current report introduces a COS-7 whole-cell binding assay and provides a
      mechanistic explanation for differential relative potencies of PeCDF among
      species of birds. 

PMID- 24434111
TI  - Sex differences in cognitive impairment and Alzheimer's disease.
AB  - Studies have shown differences in specific cognitive ability domains and risk of
      Alzheimer's disease between the men and women at later age. However it is
      important to know that sex differences in cognitive function during adulthood may
      have their basis in both organizational effects, i.e., occurring as early as
      during the neuronal development period, as well as in activational effects, where
      the influence of the sex steroids influence brain function in adulthood. Further,
      the rate of cognitive decline with aging is also different between the sexes.
      Understanding the biology of sex differences in cognitive function will not only
      provide insight into Alzheimer's disease prevention, but also is integral to the
      development of personalized, gender-specific medicine. This review draws on
      epidemiological, translational, clinical, and basic science studies to assess the
      impact of sex differences in cognitive function from young to old, and examines
      the effects of sex hormone treatments on Alzheimer's disease in men and women. 

PMID- 24434119
TI  - Oxidative stress induces mitochondrial dysfunction and a protective unfolded
      protein response in RPE cells.
AB  - How cells degenerate from oxidative stress in aging-related disease is
      incompletely understood. This study's intent was to identify key cytoprotective
      pathways activated by oxidative stress and determine the extent of their
      protection. Using an unbiased strategy with microarray analysis, we found that
      retinal pigmented epithelial (RPE) cells treated with cigarette smoke extract
      (CSE) had overrepresented genes involved in the antioxidant and unfolded protein
      response (UPR). Differentially expressed antioxidant genes were predominantly
      located in the cytoplasm, with no induction of genes that neutralize superoxide
      and H2O2 in the mitochondria, resulting in accumulation of superoxide and
      decreased ATP production. Simultaneously, CSE induced the UPR sensors IRE1alpha,
      p-PERK, and ATP6, including CHOP, which was cytoprotective because CHOP knockdown
      decreased cell viability. In mice given intravitreal CSE, the RPE had increased
      IRE1alpha and decreased ATP and developed epithelial-mesenchymal transition, as
      suggested by decreased LRAT abundance, altered ZO-1 immunolabeling, and
      dysmorphic cell shape. Mildly degenerated RPE from early age-related macular
      degeneration (AMD) samples had prominent IRE1alpha, but minimal mitochondrial
      TOM20 immunolabeling. Although oxidative stress is thought to induce an
      antioxidant response with cooperation between the mitochondria and the ER, herein
      we show that mitochondria become impaired sufficiently to induce epithelial
      mesenchymal transition despite a protective UPR. With similar responses in early
      AMD samples, these results suggest that mitochondria are vulnerable to oxidative
      stress despite a protective UPR during the early phases of aging-related disease.

PMID- 24434120
TI  - Mg supplementation protects against ritonavir-mediated endothelial oxidative
      stress and hepatic eNOS downregulation.
AB  - Ritonavir (RTV), a prototypical protease inhibitor currently used as a key
      component of anti-HIV therapy, is known for its endothelial and hepatic toxicity.
      The effects of RTV and magnesium supplementation on cultured bovine endothelial
      cell (EC) and rat hepatic endothelial nitric oxide synthase (eNOS) status were
      investigated. RTV dose-dependently (5-30 uM) decreased EC viability after 48 h;
      high Mg (2mM) significantly attenuated the lost viability. ECs incubated with 15
      uM RTV for 6 to 24h resulted in two- to fourfold elevation of oxidized
      glutathione and a 25% loss of total glutathione. At 24h, EC superoxide production
      due to RTV was detected by dihydroethidium staining and increased 41% when
      quantified by flow cytometry; altered glutathione status and superoxide levels
      were both substantially reversed by 2mM Mg. RTV reduced eNOS mRNA (-25% at 24 h)
      and led to decreased eNOS dimer/monomer ratios; nitric oxide-derived products
      decreased 40%; both changes were attenuated by Mg supplementation. In male Lewis
      Brown Norway rats, RTV administration (75 mg/kg/day, 5 weeks) resulted in an 85%
      increase in plasma 8-isoprostane and a 23% decrease in hepatic eNOS mRNA;
      concomitantly, eNOS protein decreased 75%, whereas plasma nitrite level was
      reduced 48%. Dietary Mg supplementation (sixfold higher than control) prevented
      the eNOS mRNA decrease along with lowering 8-isoprostane and restored the eNOS
      protein and plasma nitrite levels comparable to controls. In conclusion, Mg
      attenuates RTV-mediated EC oxidative eNOS dysfunction and downregulation of
      hepatic eNOS expression; we suggest that Mg can serve as a beneficial adjunct
      therapeutic against RTV-mediated eNOS toxicity.

PMID- 24434123
TI  - Nonlinear state feedback controller design for underactuated mechanical system: a
      modified block backstepping approach.
AB  - This paper presents the formulation of a novel block-backstepping based control
      algorithm to address the stabilization problem for a generalized nonlinear
      underactuated mechanical system. For the convenience of compact design, first,
      the state model of the underactuated system has been converted into the block
      strict feedback form. Next, we have incorporated backstepping control action to
      derive the expression of the control input for the generic nonlinear
      underactuated system. The proposed block backstepping technique has further been
      enriched by incorporating an integral action additionally for enhancing the
      steady state performance of the overall system. Asymptotic stability of the
      overall system has been analyzed using Lyapunov stability criteria. Subsequently,
      the stability of the zero dynamics has also been analyzed to ensure the global
      asymptotic stability of the entire nonlinear system at its desired equilibrium
      point. The proposed control algorithm has been applied for the stabilization of a
      benchmarked underactuated mechanical system to verify the effectiveness of the
      proposed control law in real-time environment. 

PMID- 24434121
TI  - Sepp1(UF) forms are N-terminal selenoprotein P truncations that have peroxidase
      activity when coupled with thioredoxin reductase-1.
AB  - Mouse selenoprotein P (Sepp1) consists of an N-terminal domain (residues 1-239)
      that contains one selenocysteine (U) as residue 40 in a proposed redox-active
      motif (-UYLC-) and a C-terminal domain (residues 240-361) that contains nine
      selenocysteines. Sepp1 transports selenium from the liver to other tissues by
      receptor-mediated endocytosis. It also reduces oxidative stress in vivo by an
      unknown mechanism. A previously uncharacterized plasma form of Sepp1 is filtered
      in the glomerulus and taken up by renal proximal convoluted tubule (PCT) cells
      via megalin-mediated endocytosis. We purified Sepp1 forms from the urine of
      megalin(-/-) mice using a monoclonal antibody to the N-terminal domain. Mass
      spectrometry revealed that the purified urinary Sepp1 consisted of N-terminal
      fragments terminating at 11 sites between residues 183 and 208. They were
      therefore designated Sepp1(UF). Because the N-terminal domain of Sepp1 has a
      thioredoxin fold, Sepp1(UF) were compared with full-length Sepp1, Sepp1(Delta240
      361), and Sepp1(U40S) as a substrate of thioredoxin reductase-1 (TrxR1). All
      forms of Sepp1 except Sepp1(U40S), which contains serine in place of the
      selenocysteine, were TrxR1 substrates, catalyzing NADPH oxidation when coupled
      with H2O2 or tert-butylhydroperoxide as the terminal electron acceptor. These
      results are compatible with proteolytic cleavage freeing Sepp1(UF) from full
      length Sepp1, the form that has the role of selenium transport, allowing
      Sepp1(UF) to function by itself as a peroxidase. Ultimately, plasma Sepp1(UF) and
      small selenium-containing proteins are filtered by the glomerulus and taken up by
      PCT cells via megalin-mediated endocytosis, preventing loss of selenium in the
      urine and providing selenium for the synthesis of glutathione peroxidase-3. 

PMID- 24434122
TI  - Partial state estimation for linear systems with output and input time delays.
AB  - This paper deals with the problem of partial state observer design for linear
      systems that are subject to time delays in the measured output as well as the
      control input. By choosing a set of appropriate augmented Lyapunov-Krasovskii
      functionals with a triple-integral term and using the information of both the
      delayed output and input, a novel approach to design a minimal-order observer is
      proposed to guarantee that the observer error is epsilon-convergent with an
      exponential rate. Existence conditions of such an observer are derived in terms
      of matrix inequalities for the cases with time delays in both the output and
      input and with output delay only. Constructive design algorithms are introduced.
      Numerical examples are provided to illustrate the design procedure, practicality
      and effectiveness of the proposed observer. 

PMID- 24434124
TI  - Uneven batch data alignment with application to the control of batch end-product
      quality.
AB  - Batch processes are commonly characterized by uneven trajectories due to the
      existence of batch-to-batch variations. The batch end-product quality is usually
      measured at the end of these uneven trajectories. It is necessary to align the
      time differences for both the measured trajectories and the batch end-product
      quality in order to implement statistical process monitoring and control schemes.
      Apart from synchronizing trajectories with variable lengths using an indicator
      variable or dynamic time warping, this paper proposes a novel approach to align
      uneven batch data by identifying short-window PCA&PLS models at first and then
      applying these identified models to extend shorter trajectories and predict
      future batch end-product quality. Furthermore, uneven batch data can also be
      aligned to be a specified batch length using moving window estimation. The
      proposed approach and its application to the control of batch end-product quality
      are demonstrated with a simulated example of fed-batch fermentation for
      penicillin production. 

PMID- 24434125
TI  - A data-driven multiplicative fault diagnosis approach for automation processes.
AB  - This paper presents a new data-driven method for diagnosing multiplicative key
      performance degradation in automation processes. Different from the well
      established additive fault diagnosis approaches, the proposed method aims at
      identifying those low-level components which increase the variability of process
      variables and cause performance degradation. Based on process data, features of
      multiplicative fault are extracted. To identify the root cause, the impact of
      fault on each process variable is evaluated in the sense of contribution to
      performance degradation. Then, a numerical example is used to illustrate the
      functionalities of the method and Monte-Carlo simulation is performed to
      demonstrate the effectiveness from the statistical viewpoint. Finally, to show
      the practical applicability, a case study on the Tennessee Eastman process is
      presented. 

PMID- 24434126
TI  - On the engineering design for systematic integration of agent-orientation in
      industrial automation.
AB  - In today's automation industry, agent-oriented development of system
      functionalities appears to have a great potential for increasing autonomy and
      flexibility of complex operations, while lowering the workload of users. In this
      paper, we present a reference model for the harmonious and systematical
      integration of agent-orientation in industrial automation. Considering
      compatibility with existing automation systems and best practice, this model
      combines advantages of function block technology, service orientation and native
      description methods from the automation standard IEC 61131-3. This approach can
      be applied as a guideline for the engineering design of future agent-oriented
      automation systems. 

PMID- 24434127
TI  - Anti-disturbance control theory for systems with multiple disturbances: a survey.
AB  - The problem of anti-disturbance control has been an eternal topic along with the
      development of the control theory. However, most methodologies can only deal with
      systems subject to a single equivalent disturbance which was merged by various
      types of uncertainties. In this paper, a review on anti-disturbance control is
      presented for systems with multiple disturbances. First, the classical control
      methods are briefly reviewed for disturbance attenuation or rejection problems.
      Then, recent advances in disturbance observer based control (DOBC) theory are
      introduced and especially, the composite hierarchical anti-disturbance control
      (CHADC) is firstly addressed. A comparison of different approaches is briefly
      carried out. Finally, focuses in the field on the current research are also
      addressed with emphasis on the practical application of the techniques. 

PMID- 24434128
TI  - Effects of a pulsatile electrostatic field on ischemic injury to the diabetic
      foot: evaluation of refractory ulcers.
AB  - AIMS: The macro- and microcirculation disease, in patients with type 2 diabetes
      mellitus (T2DM), induces ischemic wounds of the lower limbs. We have tried to
      reduce the aggregation of red blood cells and to improve the O2 supply to the
      tissues and speed the healing of ulcers in T2DM patients. METHODS: We enrolled 25
      obese subjects without glucose intolerance (group A; BMI greater than 30 kg/m2),
      20 obese adults intolerant to glucose (group B) and two subgroups, groups C and
      D, with T2DM and with leg ulcers. The groups A, B and C were treated with PESF.
      Body weight, O2 extraction, the capillary pulse, blood pressure and the surface
      of the ulcers were monitored. RESULTS: The technique PESF shows to have positive
      effects on the metabolism, on the reduction of body weight in the groups A and B,
      increasing extraction of O2 in group C and increase the speed of healing of
      wounds in group C compared to group D. In group A, there was a significant
      reduction in systolic and diastolic blood pressure. CONCLUSIONS: The technique
      PESF has affected the metabolic processes and the speed of wound healing ulcer in
      patients with T2DM.

PMID- 24434129
TI  - Management of third branchial pouch anomalies - an evolution of a minimally
      invasive technique.
AB  - OBJECTIVES: The management of third branchial pouch anomalies has evolved in
      recent times with the popularisation of the endoscopic diathermy technique to
      sclerose the pyriform fossa sinus opening. We present our experience in managing
      3 children with third branchial pouch anomalies and propose a minimally invasive
      management algorithm avoiding open neck surgery. METHODS: Retrospective case
      review of 3 patients including demographics, mode of presentation,
      investigations, management and complications. RESULTS: Three children, two male
      and one female of mean age 9.6 years presented with painful left anterior neck
      swelling. Axial neck imaging showed a superficial abscess with air locules and a
      sinus tract leading towards the left pharynx. Diagnosis was confirmed by
      endoscopic examination of the pyriform fossa revealing a sinus opening. Two
      patients underwent open excision; one combined with diathermy to the sinus
      opening. The last patient was diagnosed at his initial presentation and managed
      with endoscopic diathermy of the sinus opening combined with percutaneous needle
      aspiration of the neck abscess at the same sitting. One patient had two
      recurrences, the first after initial open surgery and the second after the first
      cautery. Two patients developed temporary hoarseness after the procedure, which
      resolved within two weeks. All patients were free from recurrences at follow-up.
      CONCLUSIONS: Introduction of the technique of endoscopic diathermy to the
      pyriform fossa sinus opening in children with third branchial pouch anomalies has
      revolutionised their management avoiding open and potentially morbid surgery. Our
      algorithm takes this further by advocating percutaneous needle aspiration of the
      infective component and performing diathermy to the sinus opening at the first
      presentation.

PMID- 24434130
TI  - Protective effect of silymarin against cisplatin-induced ototoxicity.
AB  - OBJECTIVES: Silymarin is a plant extract with strong antioxidant properties in
      addition to anti-inflammatory and anticarcinogenic actions. The aim of this study
      was to investigate the potential preventive effect of silymarin on cisplatin
      ototoxicity in an auditory cell line, HEI-OC1 cells. METHODS: Cultured HEI-OC1
      cells were exposed to cisplatin (30 MUM) with or without pre-treatment with
      silymarin (50 MUM). Cell viability was evaluated using MTT assay. Hoechst 33258
      staining was used to identify cells undergoing apoptosis. Western blot analysis
      was done to evaluate whether silymarin inhibits cisplatin-induced caspase and
      PARP activation. Cell-cycle analysis was done by flow cytometry to investigate
      whether silymarin is capable of protecting cisplatin-induced cell cycle arrest.
      RESULTS: Cell viability significantly increased in cells pretreated with
      silymarin compared with cells exposed to cisplatin alone. Pre-treatment of
      silymarin appeared to protect against cisplatin-induced apoptotic features on
      Hoechst 33258 staining. Cisplatin increased cleaved caspase-3 and PARP on Western
      blot analysis. However, pre-treatment with silymarin inhibited the expression of
      cleaved caspase-3 and PARP. Silymarin did attenuate cell cycle arrest and
      apoptosis in HEI-OC1 cells. CONCLUSIONS: Our results demonstrate that silymarin
      treatment inhibited cisplatin-induced cytotoxicity in the auditory cell line, HEI
      OC1. Silymarin may be a potential candidate drug to eliminate cisplatin induced
      ototoxicity.

PMID- 24434131
TI  - Oral communicating children using a cochlear implant: good reading outcomes are
      linked to better language and phonological processing abilities.
AB  - INTRODUCTION/OBJECTIVE: Cochlear implantation provides children with a
      significant hearing loss the potential to engage in phonological processing via
      audition; however these children can still have poor or inadequately detailed
      mental (phonological) representations of speech and as such phonological
      awareness and reading difficulties. Heterogeneous participant profiles,
      particularly varying modes of communication have clouded the research regarding
      reading outcomes of children using a cochlear implant. The objective of this
      study was to explore the relationships between word reading and reading
      comprehension outcomes, and a range of variables of a relatively homogenous group
      of children using cochlear implants. METHOD: Forty-seven oral communicating
      children using a cochlear implant and who had attended auditory-verbal therapy
      served as participants. They were administered a comprehensive battery of 10
      different assessments covering 22 different tasks across the domains of speech
      perception, speech production, language, phonological processing and reading.
      Correlation and principal component analyses were used to examine the
      relationships between outcome areas. RESULTS: Audiologic and demographic
      variables were not significantly related to reading outcomes, with the exception
      of family size. Language and word reading were most strongly related to reading
      comprehension, while phonological awareness and language were most strongly
      related to word reading. It is proposed that the development of well-specified
      phonological representations might underlie these relationships. CONCLUSION: For
      oral communicating children using a cochlear implant, good reading outcomes are
      linked to better language and phonological processing abilities.

PMID- 24434132
TI  - Effect of soil moisture on chlorine deposition.
AB  - The effect of soil moisture on chlorine (Cl(2)) deposition was examined in
      laboratory chamber experiments at high Cl(2) exposures by measuring the
      concentration of chloride (Cl(-)) in soil columns. Soil mixtures with varying
      amounts of clay, sand, and organic matter and with moisture contents up to 20%
      (w/w) were exposed to ~3*10(4)ppm Cl(2) vapor. For low water content soils,
      additional water increased the reaction rate as evidenced by higher Cl(-)
      concentration at higher soil moisture content. Results also showed that the
      presence of water restricted transport of Cl(2) into the soil columns and caused
      lower overall deposition of Cl(2) in the top 0.48-cm layer of soil when water
      filled ~60% or more of the void space in the column. Numerical solutions to
      partial differential equations of Fick's law of diffusion and a simple rate law
      for Cl(2) reaction corroborated conclusions derived from the data. For the soil
      mixtures and conditions of these experiments, moisture content that filled 30-50%
      of the available void space yielded the maximum amount of Cl(2) deposition in the
      top 0.48cm of soil.

PMID- 24434133
TI  - A RING to rule them all: RING1 as silencer and activator.
AB  - Polycomb proteins are known for silencing their target genes during development
      and cell differentiation. Reporting in Developmental Cell, Kondo et al. (2014)
      now show that Polycomb factors can also participate in gene activation by
      orchestrating the 3D chromatin structure changes involved in transcriptional
      activation of their target genes. 

PMID- 24434134
TI  - Ho(a)xing autophagy to regulate development.
AB  - In this issue of Developmental Cell, Banreti et al. (2014) demonstrate that
      canonical autophagy is inhibited in the Drosophila fat body by Hox
      transcriptional factors. This regulation involves repression of the Atg genes.
      Programmed developmental autophagy is thus under Hox control and may influence
      cell fate determination. 

PMID- 24434135
TI  - Ultrafast synaptic endocytosis cycles to the center stage.
AB  - Upon synaptic vesicle fusion, the neuronal membrane surface expands. Clathrin
      mediated endocytosis compensates for this expansion but is a slow process. Recent
      studies in eLife and Nature identify an ultrafast mode of endocytosis, occurring
      in the space between active and periactive zones, that compensates for membrane
      addition during vesicle fusion. 

PMID- 24434136
TI  - Contrasting the glial response to axon injury in the central and peripheral
      nervous systems.
AB  - Enabling axon regeneration after central nervous system (CNS) injury remains a
      major challenge in neurobiology. One of the major differences between the injured
      peripheral nervous system (PNS) and CNS is the pro- and antiregenerative
      responses of their glial cell populations. In addition to intrinsic qualities of
      the neurons themselves, glial-driven changes to the neural environment have a
      significant impact on regenerative outcome. This Review presents a comparison of
      the glial response to injury between the CNS and PNS and highlights features of
      the PNS glial response that, with continued study, might reveal long-sought-after
      keys to achieving CNS repair. 

PMID- 24434137
TI  - Making the connection: ciliary adhesion complexes anchor basal bodies to the
      actin cytoskeleton.
AB  - Cilia have been associated with diverse developmental and physiological
      processes, and defects in cilia underlie a number of genetic conditions. Several
      lines of evidence support a critical role of the actin cytoskeleton in
      ciliogenesis and ciliary function. Here, we show that well-characterized focal
      adhesion (FA) proteins, including FAK, Paxillin, and Vinculin, associate with the
      basal bodies of multiciliated cells and form complexes (CAs) that interact with
      the actin cytoskeleton. FAK downregulation leads to ciliogenesis defects similar
      to those observed when the actin cytoskeleton is disrupted, including defects in
      basal body migration, docking, and spacing, suggesting that CAs link basal bodies
      to the actin cytoskeleton. The important role of FA proteins in ciliogenesis
      leads us to propose that evolutionarily FA proteins, many of which are found in
      primitive flagellated unicellular eukaryotes, may have originally evolved to
      perform functions at flagella and were later co-opted for use in cell adhesion. 

PMID- 24434138
TI  - Small Ubiquitin-like Modifier protein SUMO enables plants to control growth
      independently of the phytohormone gibberellin.
AB  - Plants survive adverse conditions by modulating their growth in response to a
      changing environment. Gibberellins (GAs) play a key role in these adaptive
      responses by stimulating the degradation of growth-repressing DELLA proteins. GA
      binding to its receptor GID1 enables association of GID1 with DELLAs. This leads
      to the ubiquitin-mediated proteasomal degradation of DELLAs and consequently
      growth promotion. We report that DELLA-dependent growth control can be regulated
      independently of GA. We demonstrate that when a proportion of DELLAs is
      conjugated to the Small Ubiquitin-like Modifier (SUMO) protein, the extent of
      conjugation increases during stress. We identify a SUMO-interacting motif in GID1
      and demonstrate that SUMO-conjugated DELLA binds to this motif in a GA
      independent manner. The consequent sequestration of GID1 by SUMO-conjugated
      DELLAs leads to an accumulation of non-SUMOylated DELLAs, resulting in beneficial
      growth restraint during stress. We conclude that plants have developed a GA
      independent mechanism to control growth. 

PMID- 24434139
TI  - TMPRSS4 induces cancer cell invasion through pro-uPA processing.
AB  - TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed
      on the cell surface in pancreatic, thyroid, colon, and other cancer tissues.
      Previously, we demonstrated that TMPRSS4 mediates cancer cell invasion,
      epithelial-mesenchymal transition, and metastasis and that increased TMPRSS4
      expression correlates with colorectal cancer progression. We also demonstrated
      that TMPRSS4 upregulates urokinase-type plasminogen activator (uPA) gene
      expression to induce cancer cell invasion. However, it remains unknown how
      proteolytic activity of TMPRSS4 contributes to invasion. In this study, we report
      that TMPRSS4 directly converted inactive pro-uPA into the active form through its
      proteolytic activity. Analysis of conditioned medium from cells overexpressing
      TMPRSS4 demonstrated that the active TMPRSS4 protease domain is released from the
      cells and is associated with the plasma membrane. Furthermore, TMPRSS4 could
      increase pro-uPA-mediated invasion in a serine proteolytic activity-dependent
      manner. These observations suggest that TMPRSS4 is an upstream regulator of pro
      uPA activation. This study provides valuable insights into the proteolytic
      function of TMPRSS4 as well as mechanisms for the control of invasion. 

PMID- 24434140
TI  - Hepatitis B virus X protein mutant HBxDelta127 promotes proliferation of hepatoma
      cells through up-regulating miR-215 targeting PTPRT.
AB  - The mutant of virus is a frequent event. Hepatitis B virus X protein (HBx) plays
      a vital role in the development of hepatocellular carcinoma (HCC). Therefore, the
      identification of potent mutant of HBx in hepatocarcinogenesis is significant.
      Previously, we identified a natural mutant of the HBx gene (termed HBxDelta127).
      Relative to wild type HBx, HBxDelta127 strongly enhanced cell proliferation and
      migration in HCC. In this study, we aim to explore the mechanism of HBxDelta127
      in promotion of proliferation of hepatoma cells. Our data showed that both wild
      type HBx and HBxDelta127 could increase the expression of miR-215 in hepatoma
      HepG2 and H7402 cells. However, HBxDelta127 was able to significantly increase
      miR-215 expression relative to wild type HBx in the cells. We identified that
      protein tyrosine phosphatase, receptor type T (PTPRT) was one of the target genes
      of miR-215 through targeting 3'UTR of PTPRT mRNA. In function, miR-215 was able
      to promote the proliferation of hepatoma cells. Meanwhile anti-miR-215 could
      partially abolish the enhancement of cell proliferation mediated by HBxDelta127
      in vitro. Knockdown of PTPRT by siRNA could distinctly suppress the decrease of
      cell proliferation mediated by anti-miR-215 in HepG2-XDelta127/H7402-XDelta127
      cells. Moreover, we found that anti-miR-215 remarkably inhibited the tumor growth
      of hepatoma cells in nude mice. Collectively, relative to wild type HBx,
      HBxDelta127 strongly enhances proliferation of hepatoma cells through up
      regulating miR-215 targeting PTPRT. Our finding provides new insights into the
      mechanism of HBx mutant HBxDelta127 in promotion of proliferation of hepatoma
      cells. 

PMID- 24434141
TI  - The ribosomal protein rpl26 promoter is required for its 3' sense terminus ncRNA
      transcription in Schizosaccharomyces pombe, implicating a new transcriptional
      mechanism for ncRNAs.
AB  - Transcriptome studies have revealed that many non-coding RNAs (ncRNAs) are
      located near the 3' sense terminus of protein-coding genes. However, the
      transcription and function of these RNAs remain elusive. Here, we identify a 3'
      sense termini-associated sRNA (TASR) downstream of rpl26 in Schizosaccharomyces
      pombe (S. pombe). Structure and function assays indicate that the TASR is an
      H/ACA box snoRNA required for 18S rRNA pseudouridylation at U121 and U305 sites
      and is therefore a cognate of snR49 from the budding yeast. Transcriptional
      studies show that pre-snR49 overlaps most of the coding sequence (CDS) of rpl26.
      Using scanning deletion analysis within promoter region, we show that the rpl26
      promoter is required for the 3' TASR transcription. Interestingly, chromosomal
      synteny of rpl26-snR49 is found in the Schizosaccharomyces groups. Taken
      together, we have revealed a new transcriptional mechanism for 3' sense TASRs,
      which are transcribed by the same promoter as their upstream protein genes. These
      results further suggest that the origin and function of 3' sense ncRNAs are
      associated with upstream genes in higher eukaryotes. 

PMID- 24434142
TI  - Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion
      lymphoma cells.
AB  - Sangivamycin, a structural analog of adenosine and antibiotic exhibiting
      antitumor and antivirus activities, inhibits protein kinase C and the synthesis
      of both DNA and RNA. Primary effusion lymphoma (PEL) is an aggressive neoplasm
      caused by Kaposi's sarcoma-associated herpesvirus (KSHV) in immunosuppressed
      patients and HIV-infected homosexual males. PEL cells are derived from post
      germinal center B cells, and are infected with KSHV. Herein, we asked if
      sangivamycin might be useful to treat PEL. We found that sangivamycin killed PEL
      cells, and we explored the underlying mechanism. Sangivamycin treatment
      drastically decreased the viability of PEL cell lines compared to KSHV-uninfected
      B lymphoma cell lines. Sangivamycin induced the apoptosis of PEL cells by
      activating caspase-7 and -9. Further, sangivamycin suppressed the phosphorylation
      of Erk1/2 and Akt, thus inhibiting activation of the proteins. Inhibitors of Akt
      and MEK suppressed the proliferation of PEL cells compared to KSHV-uninfected
      cells. It is known that activation of Erk and Akt signaling inhibits apoptosis
      and promotes proliferation in PEL cells. Our data therefore suggest that
      sangivamycin induces apoptosis by inhibiting Erk and Akt signaling in such cells.
      We next investigated whether sangivamycin, in combination with an HSP90 inhibitor
      geldanamycin (GA) or valproate (valproic acid), potentiated the cytotoxic effects
      of the latter drugs on PEL cells. Compared to treatment with GA or valproate
      alone, the addition of sangivamycin enhanced cytotoxic activity. Our data thus
      indicate that sangivamycin may find clinical utility as a novel anti-cancer agent
      targeting PEL. 

PMID- 24434143
TI  - KB-R7943, a plasma membrane Na(+)/Ca(2+) exchanger inhibitor, blocks opening of
      the mitochondrial permeability transition pore.
AB  - The isothiourea derivative, KB-R7943, inhibits the reverse-mode of the plasma
      membrane sodium/calcium exchanger and protects against ischemia/reperfusion
      injury. The mechanism through which KB-R7943 confers protection, however, remains
      controversial. Recently, KB-R7943 has been shown to inhibit mitochondrial calcium
      uptake and matrix overload, which may contribute to its protective effects. While
      using KB-R7943 for this purpose, we find here no evidence that KB-R7943 directly
      blocks mitochondrial calcium uptake. Rather, we find that KB-R7943 inhibits
      opening of the mitochondrial permeability transition pore in permeabilized cells
      and isolated liver mitochondria. Furthermore, we find that this observation
      correlates with protection against calcium ionophore-induced mitochondrial
      membrane potential depolarization and cell death, without detrimental effects to
      basal mitochondrial membrane potential or complex I-dependent mitochondrial
      respiration. Our data reveal another mechanism through which KB-R7943 may protect
      against calcium-induced injury, as well as a novel means to inhibit the
      mitochondrial permeability transition pore. 

PMID- 24434144
TI  - Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by
      activating NF-kappaB pathway in experimental pancreatitis.
AB  - Inflammation triggered by necrotic acinar cells contributes to the
      pathophysiology of acute pancreatitis (AP), but its precise mechanism remains
      unclear. Recent studies have shown that Cyclophilin A (CypA) released from
      necrotic cells is involved in the pathogenesis of several inflammatory diseases.
      We therefore investigated the role of CypA in experimental AP induced by
      administration of sodium taurocholate (STC). CypA was markedly upregulated and
      widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and
      tubular complexes. In vitro, it was released from damaged acinar cells by
      cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced
      acinar cell necrosis, promoted nuclear factor (NF)-kappaB p65 activation, and
      increased cytokine production. In conclusion, CypA promotes pancreatic damage by
      upregulating expression of inflammatory cytokines of acinar cells via the NF
      kappaB pathway. 

PMID- 24434145
TI  - Functional characterization of Helicobacter pylori TlyA: pore-forming hemolytic
      activity and cytotoxic property of the protein.
AB  - Helicobacter pylori is a human specific gastric pathogen. H. pylori pathogenesis
      process involves a number of well-studied virulence factors that include the
      'vacuolating cytotoxin' and the 'cytotoxin associated gene A'. Analysis of the H.
      pylori genome, however, indicates presence of additional virulence factors that
      are yet to be characterized in molecular detail. For example, H. pylori genome
      harbors a gene that has potential to encode a protein with sequence similarity to
      those of the TlyA-like proteins of several pathogenic bacteria. Earlier studies
      have indicated potential association of this H. pylori tlyA gene in the virulence
      mechanism of the organism. Despite such notions, however, the TlyA-like protein
      of H. pylori has not been studied previously in molecular detail. In particular,
      purified form of H. pylori TlyA has never been studied before toward exploring
      its functional properties. Here, we report characterization of the H. pylori TlyA
      protein purified from the recombinant over-expression system in Escherichia coli.
      Purified form of the recombinant TlyA exhibits prominent hemolytic activity
      against human erythrocytes, presumably via formation of pores of specific
      diameter in the cell membrane. Purified TlyA also triggers prominent cytotoxic
      responses in human gastric adenocarcinoma cells. Altogether, our study
      establishes H. pylori TlyA as a potential virulence factor of the organism. 

PMID- 24434146
TI  - Suppression of protein kinase C-zeta attenuates vascular leakage via prevention
      of tight junction protein decrease in diabetic retinopathy.
AB  - To investigate the effect of protein kinase C (PKC)-zeta inhibition on vascular
      leakage in diabetic retinopathy, streptozotocin-induced diabetic mice were
      intravitreously injected with siPKC-zeta. According to the fluorescein
      angiography of the retinal vessels, suppression of PKC-zeta effectively
      attenuated vascular leakage in diabetic retina. Further evaluation on the retina
      with western blot analysis and immunohistochemistry revealed accompanying
      restoration of tight junction proteins on retinal vessels. As two major
      contributors to vascular leakage in diabetic retinopathy, vascular endothelial
      growth factor (VEGF) and advanced glycation end products (AGEs) were investigated
      on the tight junction protein expression in endothelial cells. Inhibition of PKC
      zeta attenuated VEGF-induced decrease of tight junction proteins and accompanying
      hyperpermeability in human retinal microvascular endothelial cells (HRMECs). PKC
      zeta inhibition also attenuated AGE-induced decrease of tight junction proteins
      in HRMECs. Our findings suggest that inhibition of PKC-zeta could be an
      alternative treatment option for compromised blood-retinal barrier in diabetic
      retinopathy. 

PMID- 24434147
TI  - Antifungal effect and mode of action of glochidioboside against Candida albicans
      membranes.
AB  - Glochidioboside was obtained from Sambucus williamsii and its biological effect
      has not been reported. Its antifungal activity against pathogenic fungi and the
      mode of action involved in its effect were examined. Glochidioboside exerted
      antifungal effect with almost no hemolytic effect against human erythrocytes. To
      understand its antifungal mechanisms, membrane studies were done. Using two dyes,
      3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)] and propidium iodide, membrane
      depolarization and permeabilization by glochidioboside were confirmed.
      Furthermore, the membrane-active mechanism was proven by synthesizing a model
      membrane, calcein-encapsulating large unilamellar vesicles (LUVs), and also by
      observing the influx of different sized fluorescent dyes, such as calcein, FD4
      and FD10, into the fungal cells. The membrane-active action was pore-forming
      action with radii between 1.4 and 2.3 nm. Finally, three dimensional (3D) flow
      cytometric analysis showed the shrinkage of the fungal cells from the membrane
      damage. In conclusion, this study suggests that glochidioboside exerts an
      antifungal activity through a membrane-disruptive mechanism.

PMID- 24434148
TI  - Fatty acid epoxyisoprostane E2 stimulates an oxidative stress response in
      endothelial cells.
AB  - Atherosclerosis is the main underlying cause of major cardiovascular diseases
      such as stroke and heart attack. Oxidized phospholipids such as oxidized 1
      palmitoyl-2-arachidonoyl-sn-Glycero-3-phosphorylcholine (OxPAPC) accumulate in
      lesions of and promote atherosclerosis. OxPAPC activates endothelial cells, a
      critical early event of atherogenesis. Epoxyisoprostane E2 (EI) is an oxidized
      fatty acid contained at the sn-2 position of 1-palmitoyl-2-epoxyisoprostane E2-sn
      glycero-3-phosphorylcholine (PEIPC), the most active component of OxPAPC in
      regulating inflammation. OxPAPC and its components including PEIPC activate
      endothelial cells to express an array of genes in different categories including
      oxidative stress response genes such as tumor suppressor gene OKL38 and Heme
      oxygenase-1 (HO-1). EI can be released by lipase from PEIPC. In this study, we
      examined the ability of EI to stimulate oxidative stress response in endothelial
      cells. EI released from OxPAPC and synthetic EI stimulated the expression of
      oxidative stress response gene OKL38 and antioxidant gene HO-1. Treatment of
      endothelial cells with EI increased the production of superoxide. NADPH oxidase
      inhibitor Apocynin and superoxide scavenger N-acetyl-cysteine (NAC) significantly
      attenuated EI-stimulated expression of OKL38 and HO-1. We further demonstrated
      that EI activated oxidative stress-sensitive transcription factor Nrf2. Silencing
      of Nrf2 with siRNA significantly reduced EI stimulated expression of OKL38 and HO
      1. Thus, we demonstrated that EI induced oxidative stress in endothelial cells
      leading to increased expression of oxidative stress response gene OKL38 and HO-1
      via Nrf2 signaling pathway relevant to atherosclerosis. 

PMID- 24434149
TI  - In-depth proteomic analyses of ovarian cancer cell line exosomes reveals
      differential enrichment of functional categories compared to the NCI 60 proteome.
AB  - Molecular communication between cancer cells and its stromal microenvironment is
      a key factor for cancer progression. Alongside classic secretory pathways, it has
      recently been proposed that small membranous vesicles are alternative mediators
      of intercellular communication. Exosomes carry an effector-rich proteome with the
      ability to modulate various functional properties of the recipient cell. In this
      study, exosomes isolated from four epithelial ovarian cancer cell lines (OVCAR3,
      OVCAR433, OVCAR5 and SKOV3) were characterized using mass spectrometry-based
      proteomics. Using an optimized workflow consisting of efficient exosome
      solubilization and the latest generation of proteomic instrumentation, we
      demonstrate improved detection depth. Systematic comparison of our cancer cell
      line exosome proteome against public data (Exocarta) and the recently published
      NCI 60 proteome revealed enrichment of functional categories related to signaling
      biology and biomarker discovery.

PMID- 24434150
TI  - Anthraquinones quinizarin and danthron unwind negatively supercoiled DNA and
      lengthen linear DNA.
AB  - The intercalating drugs possess a planar aromatic chromophore unit by which they
      insert between DNA bases causing the distortion of classical B-DNA form. The
      planar tricyclic structure of anthraquinones belongs to the group of chromophore
      units and enables anthraquinones to bind to DNA by intercalating mode. The
      interactions of simple derivatives of anthraquinone, quinizarin (1,4
      dihydroxyanthraquinone) and danthron (1,8-dihydroxyanthraquinone), with
      negatively supercoiled and linear DNA were investigated using a combination of
      the electrophoretic methods, fluorescence spectrophotometry and single molecule
      technique an atomic force microscopy. The detection of the topological change of
      negatively supercoiled plasmid DNA, unwinding of negatively supercoiled DNA,
      corresponding to appearance of DNA topoisomers with the low superhelicity and an
      increase of the contour length of linear DNA in the presence of quinizarin and
      danthron indicate the binding of both anthraquinones to DNA by intercalating
      mode. 

PMID- 24434151
TI  - Inhibitory role of Id1 on TGF-beta-induced collagen expression in human dermal
      fibroblasts.
AB  - Inhibitor of DNA binding 1 (Id1) is a basic helix-loop-helix (bHLH) protein that
      has a variety of functional roles in cellular events including differentiation,
      cell cycle and cancer development. In addition, it has been demonstrated that Id1
      is related with TGF-beta and Smad signaling in various biological conditions. In
      this study, we investigated the effect of Id1 on TGF-beta-induced collagen
      expression in human dermal fibroblasts. When Id1-b isoform was overexpressed, TGF
      beta-induced collagen expression was markedly inhibited. Consistent with this
      result, Id1-b significantly inhibited TGF-beta-induced collagen gel contraction.
      In addition, Id1-b inhibited TGF-beta-induced phosphorylation of Smad2 and Smad3.
      Finally, immunohistochemistry showed that Id1 expression was decreased in
      fibrotic skin diseases while TGF-beta signaling was increased. Together, these
      results suggest that Id1 is an inhibitory regulator on TGF-beta-induced collagen
      expression in dermal fibroblasts. 

PMID- 24434152
TI  - PTEN overexpression improves cisplatin-resistance of human ovarian cancer cells
      through upregulating KRT10 expression.
AB  - Multi-drug resistance (MDR) is a common cause of the failure of chemotherapy in
      ovarian cancer. PTEN, a tumor suppressor gene, has been demonstrated to be able
      to reverse cisplatin-resistance in ovarian cancer cell line C13K. However, the
      downstream molecules of PTEN involved in the resistance-reversing effect have not
      been completely clarified. Therefore, we screened the downstream molecules of
      PTEN and studied their interactions in C13K ovarian cancer cells using a 3D
      culture model. Firstly, we constructed an ovarian cancer cell line stably
      expressing PTEN, C13K/PTEN. MTT assay showed that overexpression of PTEN enhanced
      the sensitivity of C13K cells to cisplatin, but not to paclitaxel. Then we
      examined the differently expressed proteins that interacted with PTEN in
      C13K/PTEN cells with or without cisplatin treatment by co-immunoprecipitation.
      KRT10 was identified as a differently expressed protein in cisplatin-treated
      C13K/PTEN cells. Further study confirmed that cisplatin could induce upregulation
      of KRT10 mRNA and protein in C13K/PTEN cells and there was a directly interaction
      between KRT10 and PTEN. Forced expression of KRT10 in C13K cells also enhanced
      cisplatin-induced proliferation inhibition and apoptosis of C13K cells. In
      addition, KRT10 siRNA blocked cisplatin-induced proliferation inhibition of
      C13K/PTEN cells. In conclusion, our data demonstrate that KRT10 is a downstream
      molecule of PTEN which improves cisplatin-resistance of ovarian cancer and forced
      KRT10 overexpression may also act as a therapeutic method for overcoming MDR in
      ovarian cancer. 

PMID- 24434153
TI  - Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-kappaB
      pathway in ischemia/reperfusion-induced acute kidney injury.
AB  - BACKGROUND: The pathophysiology of ischemic acute kidney injury (AKI) is thought
      to include a complex interplay between vascular endothelial cell dysfunction,
      inflammation, and tubular cell damage. Several lines of evidence suggest a
      potential anti-inflammatory effect of vitamin D in various kidney injury models.
      In this study, we investigated the effect of paricalcitol, a synthetic vitamin D
      analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R)
      induced acute kidney injury (AKI). METHODS: Paricalcitol was administered via
      intraperitoneal (IP) injection at 24h before ischemia, and then I/R was performed
      through bilateral clamping of the renal pedicles. Twenty-four hours after I/R,
      mice were sacrificed for the evaluation of injury and inflammation. Additionally,
      an in vitro experiment using HK-2 cells was also performed to examine the direct
      effect of paricalcitol on tubular cells. RESULTS: Pre-treatment with paricalcitol
      attenuated functional deterioration and histological damage in I/R induced AKI,
      and significantly decreased tissue neutrophil and macrophage infiltration and the
      levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and
      monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced
      upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65
      subunit of NF-kappaB. Results from the in vitro study showed pre-treatment with
      paricalcitol suppressed the TNF-alpha-induced depletion of cytosolic IkappaB in
      HK-2 cells. CONCLUSION: These results demonstrate that pre-treatment with
      paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing
      TLR4-NF-kappaB mediated inflammation.

PMID- 24434154
TI  - Down-regulation of thyroid hormone receptor beta1 gene expression in gastric
      cancer involves promoter methylation.
AB  - Hypermethylation has been shown in the promoter region of the thyroid hormone
      receptor beta1 (TRbeta1) gene in several human tumors. However, its role in
      gastric cancer formation is still unclear. In the study, we analyzed mRNA
      expression of TRbeta1 gene using real-time quantitative PCR (qPCR). A
      quantitative methylation-specific PCR (Q-MSP) assay was used to determine the
      methylation status of the TRbeta1 gene promoter region in 46 pair-matched gastric
      neoplastic and adjacent non-neoplastic tissues. The results showed that TRbeta1
      mRNA expression was significantly reduced in gastric cancer specimens. The
      methylation of promoter of TRbeta1 gene in gastric cancer tissues was
      significantly higher than in adjacent normal tissues. Promoter hypermethylation
      of the TRbeta1 gene correlated with tumor infiltration, lymph node metastasis,
      and distant metastasis, but it was not associated with other clinicopathological
      characteristics. We treated gastric cancer cell lines MKN-45, MKN-28, SGC-7901,
      NCI-N87, and SNU-1 with 5-Aza-2-deoxycytidine (5-Aza-dC). The results showed the
      expression of TRbeta1 mRNA was increased in MKN-45, MKN-28, SGC-7901, but not
      increased in NCI-N87 and SNU-1. These results suggest that the TRbeta1 gene plays
      important roles in the development of gastric cancer partially through epigenetic
      mechanisms. 

PMID- 24434155
TI  - Crystal structure of FliC flagellin from Pseudomonas aeruginosa and its
      implication in TLR5 binding and formation of the flagellar filament.
AB  - Pseudomonas aeruginosa is one of leading opportunistic pathogens in humans and
      its movement is driven by a flagellar filament that is constituted through the
      polymerization of a single protein, FliC flagellin (paFliC). paFliC is an
      essential virulence factor for the colonization of P. aeruginosa. paFliC
      activates innate immune responses via its recognition by Toll-like receptor 5
      (TLR5) and adaptive immunity in the host. Thus, paFliC has been a vaccine
      candidate to prevent P. aeruginosa infection, particularly for cystic fibrosis
      patients. To provide structural information on paFliC and its flagellar filament,
      we have determined the crystal structure of paFliC, which contains the conserved
      D1 and variable D2 domains, at 2.1 A resolution. As observed for Salmonella FliC,
      the paFliC D1 domain is folded into a rod-shaped structure, and paFliC was
      demonstrated by gel filtration and native PAGE analyses to directly interact with
      TLR5. Moreover, a structural model of the paFliC-TLR5 complex suggests that
      paFliC D1 would provide major TLR5-binding sites, similar to Salmonella FliC. In
      contrast to the D1 domain, the paFliC D2 domain exhibits a unique structure of
      two beta-sheets and one alpha-helix that has not been found in other flagellins.
      An in silico construction of a flagellar filament based on the packing of paFliC
      in the crystal suggests that the D2 domain would be exposed to solution and could
      play an important role in immunogenicity. Our biophysical and structure-based
      modeling study on paFliC, the paFliC-TLR5 complex, and the paFliC filament could
      contribute to the improvement of vaccine design to control P. aeruginosa
      infection.

PMID- 24434156
TI  - Interaction with Cu2+ disrupts the RNA binding affinities of RNA recognition
      motif containing protein.
AB  - The glycine-rich proteins (GRP) containing RNA recognition motifs (RRM) are
      involved in the regulation of transcriptional and/or post-transcriptional events.
      Previous studies have established that GRP162 plays an important role in the
      restoration of fertility in Honglian cytoplasmic male sterile (HL-CMS) rice. In
      this study, the ion binding properties of rGRP162 were tested by isothermal
      titration calorimetry (ITC) and electrophoretic mobility shift assay (EMSA) was
      performed to test the interaction. Circular dichroism (CD) was carried out to
      detect the alteration of secondary structure in the presence and absence of
      Cu(2+). Furthermore, two RRM containing proteins, AtRBP45A and AtRBP47A, were
      expressed to validate the interaction. Results showed Cu(2+) and Fe(3+) bound
      GRP162, whereas Ca(2+), Mn(2+), Mg(2+) and K(+) did not. EMSA confirmed that
      interaction with Cu(2+) interrupted the biological activity of GRP162 by
      disrupting the secondary structure of the protein based on the results of CD.
      Moreover, the RNA binding activities of rAtRBP45A and rAtRBP47A were also
      impaired in the presence of Cu(2+). Data suggest that Cu(2+) in excess may
      disrupt RNA-binding proteins containing RRM that are essential for post
      transcriptional regulation and may impair the development of plants or animals. 

PMID- 24434157
TI  - Perfusion CT imaging of colorectal cancer.
AB  - Imaging plays an important role in the assessment of colorectal cancer, including
      diagnosis, staging, selection of treatment, assessment of treatment response,
      surveillance and investigation of suspected disease relapse. Anatomical imaging
      remains the mainstay for size measurement and structural evaluation; however,
      functional imaging techniques may provide additional insights into the tumour
      microenvironment. With dynamic contrast-enhanced CT techniques, iodinated
      contrast agent kinetics may inform on regional tumour perfusion, shunting and
      microvascular function and provide a surrogate measure of tumour hypoxia and
      angiogenesis. In colorectal cancer, this may be relevant for clinical practice in
      terms of tumour phenotyping, prognostication, selection of individualized
      treatment and therapy response assessment. 

PMID- 24434159
TI  - 'Living each week as unique': maternal fears in assisted reproductive technology
      pregnancies.
AB  - OBJECTIVE: to explore women's fears during pregnancy following conception via
      assisted reproductive technology (ART). METHODS: 19 expectant first-time mothers
      were interviewed during the third trimester of pregnancy using a semi-structured
      schedule. Perceptions of and feelings about pregnancy were assessed. Content
      analysis was used to identify themes and subthemes. FINDINGS: four overarching
      themes emerged: the baby's survival, the health of the baby, the efficacy of the
      mother and childbirth. Of these, the most commonly reported fears were related to
      miscarriage or fetal death, and the baby being born with an abnormality.
      CONCLUSIONS AND IMPLICATIONS: in addition to fears that are experienced by some
      women who conceived spontaneously, the women in this study who conceived via ART
      reported other fears, such as miscarriage or fetal death, that are more specific
      to this context. This suggests that these concerns should be taken into
      consideration when providing psychological support for ART mothers.

PMID- 24434158
TI  - Review of ultrasonography of malignant neck nodes: greyscale, Doppler, contrast
      enhancement and elastography.
AB  - Assessment of neck lymph nodes is essential in patients with head and neck
      cancers for predicting the patient's prognosis and selecting the appropriate
      treatment. Ultrasonography is a useful imaging tool in the assessment of neck
      lymph nodes. Greyscale ultrasonography assesses the size, distribution, and
      internal architecture of lymph nodes. Doppler ultrasonography evaluates the
      intranodal vascular pattern and resistance of lymph nodes. Contrast-enhanced
      ultrasonography provides information on lymph node parenchymal perfusion.
      Elastography allows qualitative and quantitative assessment of lymph node
      stiffness. This article reviews the value of greyscale, Doppler and contrast
      enhanced ultrasonography as well as elastography in the assessment of malignant
      nodes in the neck. 

PMID- 24434160
TI  - Effectiveness of a school-based multi-component smoking prevention intervention:
      the LdP cluster randomized controlled trial.
AB  - OBJECTIVE: We assessed the effectiveness of the Luoghi di Prevenzione-Prevention
      Grounds school-based smoking prevention programme. METHODS: We undertook a
      cluster randomized controlled trial of 989 students aged 14-15 years in 13
      secondary schools located in Reggio Emilia, Italy. The intervention consisted of
      the "Smoking Prevention Tour" (SPT) out-of-school workshop, one in-depth lesson
      on one Smoking Prevention Tour topic, a life-skills peer-led intervention, and
      enforcement surveillance of school antismoking policy. Self-reported past 30-day
      smoking of >= 20 or 1-19 days of cigarette smoking (daily or frequent smoking,
      respectively) was recorded in 2 surveys administered immediately before and 18
      months after the beginning of the programme. Analysis was by intention to treat.
      The effect of the intervention was evaluated using random effects logistic
      regression and propensity score-matching analyses. RESULTS: Past 30-day smoking
      and daily cigarette use at eighteen months follow-up were 31% and 46% lower,
      respectively, for intervention students compared to control students. Taking into
      account non-smokers at baseline only, daily smoking at eighteen months follow-up
      was 59% lower in intervention students than in controls. Past 30-day smoking in
      school areas was 62% lower in intervention students compared to controls.
      CONCLUSIONS: The Luoghi di Prevenzione-Prevention Grounds programme was effective
      in reducing daily smokers and in reducing smoking in school areas.

PMID- 24434162
TI  - Providing quality skin and wound care for the bariatric patient: an overview of
      clinical challenges.
AB  - Obesity, (defined as body mass index [BMI] >=30), and especially morbid obesity
      (defined as BMI >=40), has a profound impact on the health and integrity of the
      patient's integumentary system and on the caregivers who strive to provide care
      for larger, heavy patients. The purpose of this overview is to address some
      common skin and wound care issues faced by bariatric patients in order to inform
      clinicians, patients, and caregivers and enable them to optimize care. For
      bariatric patients, extra attention must be paid to skin care, cleanliness, skin
      fold management, perigenital care, odor management, and effective pressure
      redistribution. Despite these interventions, the multifactorial challenges
      presented by morbid obesity increase patient risk for serious skin diseases and
      wound conditions. Implications for practice include how best to educate patients
      and caregivers for optimal problem prevention. Future research should target
      improving bariatric care equipment and decreasing risk indices. 

PMID- 24434163
TI  - The role of obesity in the patient undergoing colorectal surgery and fecal
      diversion: a review of the literature.
AB  - The obese colorectal surgery patient may face several challenges, including a
      high risk for the development of colorectal cancer, an increased risk for
      complications with diverticular disease, and surgical risk factors including
      anastomotic leaks, inability to perform a low anastomosis, and septic
      complications. The purpose of this literature review was to examine available
      data on the implications of obesity on colorectal disease and colorectal surgery,
      particularly stoma surgery. Obesity has been documented as a risk factor for
      colorectal disease, but results of studies examining surgeryrelated problems
      secondary to obesity are inconsistent. However, clinicians generally believe
      obese patients undergoing colorectal surgery may be at higher risk of
      complications than their non-obese counterparts. The obese patient requiring the
      creation of a fecal diversion may encounter stoma-related issues such as
      stenosis, retraction, and inability to maintain a consistent pouching system
      seal. Stoma site marking can be challenging because of the large shifts in
      subcutaneous tissue and the inability for a person with a large abdomen to be
      able to visualize the stoma if the stoma is placed too low on the abdomen.
      Additional research to elucidate complication rates and risk factors is needed to
      help clinicians develop optimal plans of care. 

PMID- 24434161
TI  - Association of depressive symptoms, trait anxiety, and perceived stress with
      subclinical atherosclerosis: results from the Chicago Healthy Aging Study (CHAS).
AB  - OBJECTIVE: Examine the association between multiple psychological factors
      (depressive symptoms, trait anxiety, perceived stress) and subclinical
      atherosclerosis in older age. METHOD: This cross-sectional study included 1101
      adults ages 65-84 from the Chicago Healthy Aging Study (CHAS - 2007-2010).
      Previously validated self-report instruments were used to assess psychological
      factors. Non-invasive methods were used to assess subclinical atherosclerosis in
      two regions of the body, i.e., ankle-brachial blood pressure index (ABI) and
      coronary artery calcification (CAC). Multivariate logistic regression was used to
      examine the association between each psychological measure and subclinical
      atherosclerosis, after the adjustment for socio-demographic factors, sleep
      quality, young adulthood/early middle age and late-life CVD risk status, and
      psychological ill-being as appropriate. RESULTS: The burden of major
      cardiovascular disease risk factors did not significantly differ across tertiles
      of psychological factors. In multivariate adjusted models, trait anxiety was
      associated with calcification: those in the second tertile were significantly
      more likely to have CAC >0 compared to those in the lowest anxiety tertile
      [OR=1.68; 95% CI=1.09-2.58], but no significant difference was observed for
      Tertile III of trait anxiety [OR=1.31; 95% CI=0.75-2.27]. No association was seen
      between psychological measures and ABI. CONCLUSION: Of several psychological
      factors, only trait anxiety was significantly associated with CAC.

PMID- 24434164
TI  - Massive localized lymphedema, a disease unique to the morbidly obese: a case
      study.
AB  - Massive localized lymphedema (MLL) is a unique presentation of lymphedema
      resulting in a large, benign, painless mass that develops in morbidly obese
      patients, most commonly on the medial thigh. Because nearly 6% of the United
      States adult population is morbidly obese, MLL is believed to be under-diagnosed.
      To better guide the clinician in identifying and treating MLL, a case study of a
      44-year-old Caucasian woman with type I diabetes who presented to the study wound
      care clinic with MLL is reported, along with the experience of managing more than
      70 patients with MLL. A diagnosis of MLL is usually made based on clinical
      history and presentation. Routine tissue biopsy is not advisable, and diagnostic
      tests such as magnetic resonance imaging (MRI) may be impossible due to the
      morbid obesity of most patients. Complete decongestive physiotherapy (CDP) is
      recommended. Although surgical removal of the MLL collection may be possible, it
      is technically difficult and not always advisable due to the risk of
      perioperative complications, including wound dehiscence. Furthermore, in the
      author's experience, recurrence is possible even after surgical removal,
      particularly if conscientious adherence to compression and weight management do
      not continue. The advent of advanced pneumatic compression devices designed for
      the morbidly obese and the possibility of using near-infrared fluorescence
      imaging to guide treatment may transform the MLL management process. Considering
      the increasing number of MLL cases, the comorbidities and complexities of
      treating morbidly obese patients, and associated complications, clinicians caring
      for the morbidly obese need a heightened awareness of this condition. 

PMID- 24434165
TI  - A pictorial overview of technology-assisted care options for bariatric patients:
      one hospital's experience.
AB  - Best practice guidelines to avoid pressure ulcers and skin breakdown among obese
      patients include early and progressive mobility, rigorous turning schedules, and
      proper skin care. However, implementation of some these guidelines may increase
      the risk of patient and caregiver injury. An acute care hospital implemented safe
      patient handling protocols that involved equipment purchase and extensive
      training for all care staff. The new equipment facilitated repositioning,
      including boosting and turning, lateral transfers, vertical transfers and
      ambulation, and bathing and toileting. All healthcare facilities are expected to
      see an increase in the number of bariatric patients and need for safe patient
      handling protocols and procedures. At the same time, research is needed to
      evaluate the safety, effectiveness, and cost-effectiveness of currently available
      devices designed to improve patient safety and reduce caregiver injury. 

PMID- 24434167
TI  - One size does not fit all: matching patients with insomnia treatment modality.

PMID- 24434166
TI  - Automatic detection of subsolid pulmonary nodules in thoracic computed tomography
      images.
AB  - Subsolid pulmonary nodules occur less often than solid pulmonary nodules, but
      show a much higher malignancy rate. Therefore, accurate detection of this type of
      pulmonary nodules is crucial. In this work, a computer-aided detection (CAD)
      system for subsolid nodules in computed tomography images is presented and
      evaluated on a large data set from a multi-center lung cancer screening trial.
      The paper describes the different components of the CAD system and presents
      experiments to optimize the performance of the proposed CAD system. A rich set of
      128 features is defined for subsolid nodule candidates. In addition to previously
      used intensity, shape and texture features, a novel set of context features is
      introduced. Experiments show that these features significantly improve the
      classification performance. Optimization and training of the CAD system is
      performed on a large training set from one site of a lung cancer screening trial.
      Performance analysis on an independent test from another site of the trial shows
      that the proposed system reaches a sensitivity of 80% at an average of only 1.0
      false positive detections per scan. A retrospective analysis of the output of the
      CAD system by an experienced thoracic radiologist shows that the CAD system is
      able to find subsolid nodules which were not contained in the screening database.

PMID- 24434168
TI  - Planarian D-amino acid oxidase is involved in ovarian development during sexual
      induction.
AB  - To elucidate the molecular mechanisms underlying switching from asexual to sexual
      reproduction, namely sexual induction, we developed an assay system for sexual
      induction in the hermaphroditic planarian species Dugesia ryukyuensis. Ovarian
      development is the initial and essential step in sexual induction, and it is
      followed by the formation of other reproductive organs, including the testes.
      Here, we report a function of a planarian D-amino acid oxidase, Dr-DAO, in the
      control of ovarian development in planarians. Asexual worms showed significantly
      more widespread expression of Dr-DAO in the parenchymal space than did sexual
      worms. Inhibition of Dr-DAO by RNAi caused the formation of immature ovaries. In
      addition, we found that feeding asexual worms 5 specific D-amino acids could
      induce the formation of immature ovaries that are similar to those observed in Dr
      DAO knockdown worms, suggesting that Dr-DAO inhibits the formation of immature
      ovaries by degrading these D-amino acids. Following sexual induction, Dr-DAO
      expression was observed in the ovaries. The knockdown of Dr-DAO during sexual
      induction delayed the maturation of the other reproductive organs, as well as
      ovary. These findings suggest that Dr-DAO acts to promote ovarian maturation and
      that complete sexual induction depends on the production of mature ovaries. We
      propose that Dr-DAO produced in somatic cells prevents the onset of sexual
      induction in the asexual state, and then after sexual induction, the female germ
      cells specifically produce Dr-DAO to induce full maturation. Therefore, Dr-DAO
      produced in somatic and female germline cells may play different roles in sexual
      induction.

PMID- 24434169
TI  - 454 pyrosequencing-based analysis of gene expression profiles in the amphipod
      Melita plumulosa: transcriptome assembly and toxicant induced changes.
AB  - Next generation sequencing using Roche's 454 pyrosequencing platform can be used
      to generate genomic information for non-model organisms, although there are
      bioinformatic challenges associated with these studies. These challenges are
      compounded by a lack of a standardized protocol to either assemble data or to
      evaluate the quality of a de novo transcriptome. This study presents an assembly
      of the control and toxicant responsive transcriptome of Melita plumulosa, an
      Australian amphipod commonly used in ecotoxicological studies. RNA was harvested
      from control amphipods, juvenile amphipods, and from amphipods exposed to either
      metal or diesel contaminated sediments. This RNA was used as the basis for a 454
      based transcriptome sequencing effort. Sequencing generated 1.3 million reads
      from control, juvenile, metal-exposed and diesel-exposed amphipods. Different
      read filtering and assembly protocols were evaluated to generate an assembly that
      (i) had an optimal number of contigs; (ii) had long contigs; (iii) contained a
      suitable representation of conserved genes; and (iv) had long ortholog alignment
      lengths relative to the length of each contig. A final assembly, generated using
      fixed-length trimming based on the sequence quality scores, followed by assembly
      using the MIRA algorithm, produced the best results. The 26,625 contigs generated
      via this approach were annotated using Blast2GO, and the differential expression
      between treatments and control was determined by mapping with BWA followed by
      DESeq. Although the mapping generated low coverage, many differentially expressed
      contigs, including some with known developmental or toxicological function, were
      identified. This study demonstrated that 454 pyrosequencing is an effective means
      of generating reference transcriptome information for organisms, such as the
      amphipod M. plumulosa, that have no genomic information available in databases or
      in closely related sequenced species. It also demonstrated how optimization of
      read filtering protocols and assembly approaches changes the utility of results
      obtained from next generation sequencing studies, and establishes criteria to
      determine the quality of a de novo assembly in species lacking a reference
      genome. This new transcriptomic knowledge provides the genomic foundation for the
      creation of microarray and qPCR assays, serving as a reference transcriptome in
      future RNAseq studies, and allowing both the biology and ecotoxicology of this
      organism to be better understood. This approach will allow genomics-based
      methodology to be applied to a wider range of environmentally relevant species. 

PMID- 24434170
TI  - Selective extraction of PAHs from a sediment with structural preservation of
      Natural Organic Matter.
AB  - Selective extraction of Polycyclic Aromatic Hydrocarbons (PAH) without structural
      modification of the Natural Organic Matter (NOM) from a heavily contaminated
      sediment was investigated using various solvents mixtures. Structural
      modification of the NOM was monitored after extraction using 3D-fluorescence
      spectroscopy. Better results were obtained with a 15-h PAH extraction under
      reflux with a dichloromethane/cyclohexane 20/80 mixture. The experimental
      procedure was validated with NOM standard materials before to be applied on
      natural sediments. It could be applied to any environmental solid sample such as
      sediments and soils. 

PMID- 24434171
TI  - Note from the editors: a busy and eventful year has passed.

PMID- 24434172
TI  - A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance
      to oseltamivir and peramivir in Japan, November to December 2013.
AB  - Six influenza A(H1N1)pdm09 viruses were detected in Sapporo, Japan, between
      November and December 2013. All six viruses possessed an H275Y substitution in
      the neuraminidase protein, which confers cross-resistance to oseltamivir and
      peramivir. No epidemiological link among the six cases could be identified; none
      of them had received neuraminidase inhibitors before specimen collection. The
      haemagglutinin and neuraminidase genes of the six viruses were closely related to
      one another, suggesting clonal spread of a single resistant virus.

PMID- 24434173
TI  - An outbreak of Salmonella Newport associated with mung bean sprouts in Germany
      and the Netherlands, October to November 2011.
AB  - The largest Salmonella enterica serovar Newport outbreak (n=106) ever reported in
      Germany occurred in October and November 2011. Twenty associated cases were
      reported in the Netherlands. The outbreak investigation included an analytical
      epidemiological study, molecular typing of human and food isolates and food
      traceback investigations. Unspecified Salmonella had been detected in samples of
      mung bean sprouts at a sprout producer (producer A) in the Netherlands and mung
      bean sprouts contaminated with S. Newport had been found during routine sampling
      at a sprout distributor in Germany. Therefore, we tested the hypothesis of
      sprouts being the infection vehicle. In a case-control study, we compared 50
      notified adult S. Newport cases with 45 Salmonella enterica serovar Enteritidis
      cases regarding their food consumption in the three days before illness. In
      multivariable logistic regression analysis, only sprout consumption was
      significantly associated with S. Newport infection (odds ratio: 18.4; 95%
      confidence interval: 2.2-150.2). Molecular typing patterns of human isolates were
      indistinguishable from a mung bean sprouts isolate. Traceback of sprouts led to
      distributors and producer A in the Netherlands. Since sprouts are frequently
      contaminated with microorganisms, consumers need to be aware that consumption of
      raw or insufficiently cooked sprouts may pose a health risk.

PMID- 24434174
TI  - The French human Salmonella surveillance system: evaluation of timeliness of
      laboratory reporting and factors associated with delays, 2007 to 2011.
AB  - Given the regular occurrence of salmonellosis outbreaks in France, evaluating the
      timeliness of laboratory reporting is critical for maintaining an effective
      surveillance system. Laboratory-confirmed human cases of Salmonella infection
      from whom strains were isolated from 2007 to 2011 in France (n=38,413) were
      extracted from the surveillance database. Three delay intervals were defined:
      transport delay (strain isolation, transport from primary laboratory to national
      reference laboratory), analysis delay (serotyping, reporting) and total reporting
      delay. We calculated the median delay in days and generated the cumulative delay
      distribution for each interval. Variables were tested for an association with
      reporting delay using a multivariable generalised linear model. The median
      transport and analysis delays were 7 and 6 days respectively (interquartile range
      (IQR: 6-10 and 4-9 respectively), with a median total reporting delay of 14 days
      (IQR: 11-19). Timeliness was influenced by various external factors: decreasing
      serotype frequency, geographical zone of primary laboratory and strain isolation
      on Sundays were the variables most strongly associated with increased length of
      delay. The effect of season and day of the week of isolation was highly variable
      over the study period. Several areas for interventions to shorten delays are
      identified and discussed for both transport and analysis delays.

PMID- 24434175
TI  - The Danish Microbiology Database (MiBa) 2010 to 2013.
AB  - The Danish Microbiology Database (MiBa) is a national database that receives
      copies of reports from all Danish departments of clinical microbiology. The
      database was launched in order to provide healthcare personnel with nationwide
      access to microbiology reports and to enable real-time surveillance of
      communicable diseases and microorganisms. The establishment and management of
      MiBa has been a collaborative process among stakeholders, and the present paper
      summarises lessons learned from this nationwide endeavour which may be relevant
      to similar projects in the rapidly changing landscape of health informatics.

PMID- 24434176
TI  - Conclusions of the fourth CONSISE international meeting.

PMID- 24434180
TI  - Flying blind in American orthopaedic surgery: the urgent need for an educational
      curriculum in orthopaedic surgery residency training.

PMID- 24434181
TI  - Autoregressive cross-lagged models of IMPACT-III and Pediatric Crohn's Disease
      Activity Indexes during one year infliximab therapy in pediatric patients with
      Crohn's disease.
AB  - BACKGROUND: Quality of life (QoL) is an important outcome measure in the
      evaluation of therapies for inflammatory bowel disease. The primary aim of this
      study was to determine the effect of one year infliximab treatment on QoL and
      clinical parameters in pediatric patients with Crohn's diseases (CD). METHODS:
      Our prospective study involved 51 children with conventional therapy resistant,
      severe CD (mean age: 15.25years, range: 11-18years). Infliximab was given
      according to the protocol (5mg/kg, at weeks 0, 2, 6 and every 8weeks). During the
      infliximab courses QoL of patients was evaluated by IMPACT-III questionnaire at
      weeks 0, 6, 30 and 53. At the same time, the Pediatric Crohn's Disease Activity
      Index (PCDAI) score was calculated. Moreover, serum C-reactive protein (CRP),
      serum platelets and serum albumin were followed up. Auto-regressive, cross-lagged
      models were used to assess relation between QoL and the clinical parameters.
      RESULTS: The initial IMPACT-III scores [median, percentile 25-75 (pc 25-75) at
      week 0: 115, 102.5-130.25] increased significantly (p<0.001) following infliximab
      therapy at week 54 (median: 141.5, 124.5-153.75). Clinical and laboratory
      parameters also improved significantly (p<0.001). Auto-regressive regression
      coefficients (beta value) were significant between each variable over time. The
      strongest cross-lagged relations were observed between IMPACT-III and serum
      albumin, IMPACT-III and platelets. Reliability test of IMPACT-III revealed an
      excellent level of internal consistency (Cronbach's alpha=0.931). CONCLUSION:
      Infliximab treatment has beneficial clinical effect which is confirmed by
      decrease of PCDAI and increase of IMPACT-III. Autoregressive regression analysis
      showed regression relation between IMPACT-III and PCDAI and laboratory
      parameters.

PMID- 24434182
TI  - Increased hospitalizations in elderly with inflammatory bowel disease on anti
      tumor necrosis factor therapy but not increased infections: a community practice
      experience.

PMID- 24434184
TI  - FGF23 promotes renal calcium reabsorption through the TRPV5 channel.
AB  - alphaKlotho is thought to activate the epithelial calcium channel Transient
      Receptor Potential Vanilloid-5 (TRPV5) in distal renal tubules through its
      putative glucuronidase/sialidase activity, thereby preventing renal calcium loss.
      However, alphaKlotho also functions as the obligatory co-receptor for fibroblast
      growth factor-23 (FGF23), a bone-derived phosphaturic hormone. Here, we show that
      renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in
      Fgf23 knockout mice, similar to what is seen in alphaKlotho knockout mice. We
      further demonstrate that alphaKlotho neither co-localizes with TRPV5 nor is
      regulated by FGF23. Rather, apical membrane abundance of TRPV5 in renal distal
      tubules and thus renal calcium reabsorption are regulated by FGF23, which binds
      the FGF receptor-alphaKlotho complex and activates a signaling cascade involving
      ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not alphaKlotho, as a
      calcium-conserving hormone in the kidney. 

PMID- 24434185
TI  - Quetiapine responsive catatonia in an autistic patient with comorbid bipolar
      disorder and idiopathic basal ganglia calcification.
AB  - BACKGROUND: Bipolar disorder (BD) has been linked with the manifestation of
      catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal
      ganglia calcification (IBGC) is characterized by movement disorders and various
      neuropsychiatric disturbances including mood disorder. CASE: We present a patient
      with ASD and IBGC who developed catatonia presenting with prominent dystonic
      feature caused by comorbid BD, which was treated effectively with quetiapine.
      CONCLUSION: In addition to considering the possibility of neurodegenerative
      disease, careful psychiatric interventions are important to avoid overlooking
      treatable catatonia associated with BD in cases of ASD presenting with both
      prominent dystonic features and apparent fluctuation of the mood state.

PMID- 24434186
TI  - Physical activity and risk of gastric cancer: a meta-analysis of observational
      studies.
AB  - BACKGROUND: Studies evaluating the relationship of physical activity and stomach
      cancer risk have yielded inconsistent and largely inconclusive results. We
      therefore conducted a systematic review and meta-analysis of observational
      studies that assessed the relationship between physical activity and risk of
      gastric cancer. METHODS: Following a standard protocol, we searched medical
      literature databases (PubMed, EMBASE, CINAHL, PsycINFO and Google Scholar) from
      inception to July 2012, and conducted a random effects meta-analysis. RESULTS:
      Seven prospective cohorts and four case-control studies of physical activity and
      gastric cancer risk, with 1,535,006 people and 7944 cases of gastric cancer were
      included. We found a modest protective association between sufficient physical
      activity and gastric cancer risk (relative risk: 0.81 (95% CI 0.69 to 0.96);
      I(2)=68.5%) in the prospective studies and (relative risk: 0.78 (95% CI 0.66 to
      0.91); I(2)=0%) in case-control studies. The association appeared weaker in
      smokers than in non-smokers (p heterogeneity=0.035). The association may also be
      weaker for gastric cardia cancer relative to the distal non-cardia subtypes.
      Physical activity type (recreational or occupational), intake of alcohol, total
      energy intake, consumption of fruits and vegetables and infection with
      Helicobacter pylori had no influence on the association. The effect measure from
      cohort studies (relative risk: 0.82 (95% CI 0.70 to 0.97); I(2)=61.7%) and case
      control studies (relative risk: 0.83 (95% CI 0.66 to 1.04); I(2)=49.8%) did not
      differ materially at higher physical activity levels. CONCLUSIONS: We conclude
      that a regular physical activity may be protective against stomach cancer risk.

PMID- 24434187
TI  - Advance care planning for adults with CKD: a systematic integrative review.
AB  - BACKGROUND: Recent clinical practice guidelines have highlighted the importance
      of advance care planning (ACP) for improving end-of-life care for people with
      chronic kidney disease (CKD). STUDY DESIGN: We conducted a systematic integrative
      review of the literature to inform future ACP practice and research in CKD,
      searching electronic databases in April 2013. Synthesis used narrative methods.
      SETTING & POPULATION: We focused on adults with a primary diagnosis of CKD in any
      setting. SELECTION CRITERIA FOR STUDIES: We included studies of any design,
      quantitative or qualitative. INTERVENTIONS: ACP was defined as any formal means
      taken to ensure that health professionals and family members are aware of
      patients' wishes for care in the event they become too unwell to speak for
      themselves. OUTCOMES: Measures of all kinds were considered of interest. RESULTS:
      55 articles met criteria reporting on 51 discrete samples. All patient samples
      included people with CKD stage 5; 2 also included patients with stage 4. Seven
      interventions were tested; all were narrowly focused and none was evaluated by
      comparing wishes for end-of-life care with care received. One intervention
      demonstrated effects on patient and family outcomes in the form of improved well
      being and anxiety following sessions with a peer mentor. Insights from
      qualitative studies that have not been used to inform interventions include the
      importance of instilling patient confidence that their advance directives will be
      enacted and discussing decisions about (dis)continuing dialysis therapy
      separately from "aggressive" life-sustaining treatments (eg, ventilation).
      LIMITATIONS: Although quantitative and qualitative findings were integrated
      according to best practice, methods for this are in their infancy. CONCLUSIONS:
      Research on ACP in patients with CKD is limited, especially intervention studies.
      Interventions in CKD should attend to barriers and facilitators at the levels of
      patient, caregiver, health professional, and system. Intervention studies should
      measure impact on compliance with patient wishes for end-of-life care.

PMID- 24434188
TI  - Convective versus diffusive dialysis therapies for chronic kidney failure: an
      updated systematic review of randomized controlled trials.
AB  - BACKGROUND: Convective dialysis therapies (hemofiltration or hemodiafiltration)
      are associated with lower mortality compared to hemodialysis in observational
      studies. A previous meta-analysis of randomized trials comparing convective
      modalities with hemodialysis in 2006 was inconclusive due to insufficient data.
      Additional randomized trials recently have reported conflicting results. STUDY
      DESIGN: Systematic review and meta-analysis of randomized trials to February 27,
      2013. SETTING & POPULATION: Patients with chronic kidney failure treated by
      hemodialysis, hemodiafiltration, hemofiltration, or biofiltration. SELECTION
      CRITERIA FOR STUDIES: Randomized controlled trials. INTERVENTION: Convective
      therapies (hemodiafiltration, hemofiltration, and acetate-free biofiltration)
      compared with hemodialysis. OUTCOMES: All-cause and cardiovascular mortality,
      nonfatal cardiovascular events, hospitalization, change in dialysis modality,
      health-related quality of life, adverse events, blood pressure, and clearances of
      urea and beta2-microglobulin. RESULTS: 35 trials (4,039 participants) were
      included. In low-quality evidence, convective dialysis had little or no effect on
      all-cause mortality (relative risk [RR], 0.87; 95% CI, 0.70-1.07) and may reduce
      cardiovascular mortality (RR, 0.75; 95% CI, 0.58-0.97) and hypotension (RR, 0.72;
      95% CI, 0.66-0.80) during dialysis, but had uncertain effects on nonfatal
      cardiovascular events (RR, 1.14; 95% CI, 0.85-1.52) and hospitalization (RR,
      1.21; 95% CI, 0.12-12.05). Adverse events were not reported systematically and
      health-related quality-of-life outcomes were sparse. Convective therapies reduced
      predialysis levels of beta2-microglobulin (mean difference, -5.77 [95% CI, -10.97
      to -0.56]mg/dL) and increased dialysis dose (Kt/Vurea mean difference, 0.10; 95%
      CI, 0.02-0.19), but these effects were very heterogeneous. Sensitivity analyses
      limited to trials comparing hemodiafiltration with hemodialysis showed similar
      results. LIMITATIONS: Studies had important risks of bias leading to low
      confidence in the summary estimates and generally were limited to patients who
      had adequate dialysis vascular access. CONCLUSIONS: Treatment effects of
      convective dialysis are unreliable due to limitations in trial methods and
      reporting. Convective dialysis may reduce cardiovascular but not all-cause
      mortality, and effects on nonfatal cardiovascular events and hospitalization are
      inconclusive.

PMID- 24434189
TI  - A novel fluorometric assay for aldo-keto reductase 1C3 predicts metabolic
      activation of the nitrogen mustard prodrug PR-104A in human leukaemia cells.
AB  - Aldo-keto reductase 1C3 (AKR1C3, EC 1.1.1.188) metabolises steroid hormones,
      prostaglandins and xenobiotics, and activates the dinitrobenzamide mustard
      prodrug PR-104A by reducing it to hydroxylamine PR-104H. Here, we describe a
      functional assay for AKR1C3 in cells using the fluorogenic probe coumberone (a
      substrate for all AKR1C isoforms) in conjunction with a specific inhibitor of
      AKR1C3, the morpholylurea SN34037. We use this assay to evaluate AKR1C3 activity
      and PR-104A sensitivity in human leukaemia cells. SN34037-sensitive reduction of
      coumberone to fluorescent coumberol correlated with AKR1C3 protein expression by
      immunoblotting in a panel of seven diverse human leukaemia cell lines, and with
      SN34037-sensitive reduction of PR-104A to PR-104H. SN34037 inhibited aerobic
      cytotoxicity of PR-104A in high-AKR1C3 TF1 erythroleukaemia cells, but not in low
      AKR1C3 Nalm6 pre-B cell acute lymphocytic leukaemia (B-ALL) cells, although
      variation in PR-104H sensitivity confounded the relationship between AKR1C3
      activity and PR-104A sensitivity across the cell line panel. AKR1C3 mRNA
      expression showed wide variation between leukaemia patients, with consistently
      higher levels in T-ALL than B-ALL. In short term cultures from patient-derived
      paediatric ALL xenografts, PR-104A was more potent in T-ALL than B-ALL lines, and
      PR-104A cytotoxicity was significantly inhibited by SN34037 in T-ALL but not B
      ALL. Overall, the results demonstrate that SN34037-sensitive coumberone reduction
      provides a rapid and specific assay for AKR1C3 activity in cells, with potential
      utility for identifying PR-104A-responsive leukaemias. However, variations in PR
      104H sensitivity indicate the need for additional biomarkers for patient
      stratification. 

PMID- 24434191
TI  - Socioeconomic status and heart failure in Sydney.
AB  - BACKGROUND: Socioeconomic disadvantage is associated with an increased risk of
      developing heart failure and with inferior health outcomes following diagnosis.
      METHODS: Data for hospitalisations and deaths due to heart failure in the Sydney
      metropolitan region were extracted from New South Wales hospital records and
      Australian Bureau of Statistics databases for 1999-2003. Standardised rates were
      analysed according to patients' residential local government area and correlated
      with an index of socioeconomic disadvantage. RESULTS: Eight of the 13 local
      government areas with standardised separation rate ratios significantly higher
      than all NSW, and those with the six highest standardised separation rate ratios,
      were in Greater Western Sydney. Rates of heart failure hospitalisations per local
      government area were inversely correlated with level of socioeconomic status.
      CONCLUSIONS: Higher rates of heart failure hospitalisations among residents of
      socioeconomically disadvantaged regions within Sydney highlight the need for
      strategies to lessen the impact of disadvantage and strategies to improve
      cardiovascular health.

PMID- 24434192
TI  - An informatics framework for the standardized collection and analysis of
      medication data in networked research.
AB  - Medication exposure is an important variable in virtually all clinical research,
      yet there is great variation in how the data are collected, coded, and analyzed.
      Coding and classification systems for medication data are heterogeneous in
      structure, and there is little guidance for implementing them, especially in
      large research networks and multi-site trials. Current practices for handling
      medication data in clinical trials have emerged from the requirements and
      limitations of paper-based data collection, but there are now many electronic
      tools to enable the collection and analysis of medication data. This paper
      reviews approaches to coding medication data in multi-site research contexts, and
      proposes a framework for the classification, reporting, and analysis of
      medication data. The framework can be used to develop tools for classifying
      medications in coded data sets to support context appropriate, explicit, and
      reproducible data analyses by researchers and secondary users in virtually all
      clinical research domains. 

PMID- 24434190
TI  - Therapeutic implications of the prostaglandin pathway in Alzheimer's disease.
AB  - An important pathologic hallmark of Alzheimer's disease (AD) is
      neuroinflammation, a process characterized in AD by disproportionate activation
      of cells (microglia and astrocytes, primarily) of the non-specific innate immune
      system within the CNS. While inflammation itself is not intrinsically
      detrimental, a delicate balance of pro- and anti-inflammatory signals must be
      maintained to ensure that long-term exaggerated responses do not damage the brain
      over time. Non-steroidal anti-inflammatory drugs (NSAIDs) represent a broad class
      of powerful therapeutics that temper inflammation by inhibiting cyclooxygenase
      mediated signaling pathways including prostaglandins, which are the principal
      mediators of CNS neuroinflammation. While historically used to treat discrete or
      systemic inflammatory conditions, epidemiologic evidence suggests that protracted
      NSAID use may delay AD onset, as well as decrease disease severity and rate of
      progression. Unfortunately, clinical trials with NSAIDs have thus far yielded
      disappointing results, including premature discontinuation of a large-scale
      prevention trial due to unexpected cardiovascular side effects. Here we review
      the literature and make the argument that more targeted exploitation of
      downstream prostaglandin signaling pathways may offer significant therapeutic
      benefits for AD while minimizing adverse side effects. Directed strategies such
      as these may ultimately help to delay the deleterious consequences of brain aging
      and might someday lead to new therapies for AD and other chronic
      neurodegenerative diseases. 

PMID- 24434195
TI  - pVEGF-loaded lipopolysaccharide-amine nanopolymersomes for therapeutic
      angiogenesis.
AB  - Therapeutic angiogenesis via gene delivery is promising for tissue survival and
      regeneration after injury or ischemia. A stable, safe and efficient gene vector
      is essential for successful angiogenesis. We have demonstrated that our newly
      developed lipopolysaccharide-amine nanopolymersomes (LNPs) have higher than 95%
      transfection efficiency when delivering pEGFP into mesenchymal stem cells (MSCs).
      To explore their clinical potential in therapeutic angiogenesis, in this study,
      we studied their toxicity, storage stability, protection ability to genes and
      efficacy to deliver therapeutic genes of pVEGF in MSCs and zebrafish. The results
      show that LNPs can condense pVEGF to form pVEGF-loaded nanopolymersomes (VNPs),
      and protect pVEGF against DNase digestion in 6 h. Both LNPs and VNPs have low
      toxicity to MSCs, erythrocytes and zebrafish embryos. LNPs are stable at 4 
      degrees C for at least two years with unchanged size and transfection efficiency.
      MSCs transfected by VNPs continuously synthesize VEGF for at least four days
      under control, with a peak (21.25 ng ml(-1)) ~35-fold greater than that for the
      untreated group. VNPs induce significant and dose-dependent angiogenesis in
      zebrafish without causing death, deformity or delay in growth and development,
      and the induced maximal vessel area of subintestinal vessel plexus is 2.5-fold
      higher than that for the untreated group. Our study suggests that VNP has high
      potential in therapeutic angiogenesis.

PMID- 24434194
TI  - Evidence for altered amygdala activation in schizophrenia in an adaptive emotion
      recognition task.
AB  - Deficits in social cognition seem to present an intermediate phenotype for
      schizophrenia, and are known to be associated with an altered amygdala response
      to faces. However, current results are heterogeneous with respect to whether this
      altered amygdala response in schizophrenia is hypoactive or hyperactive in
      nature. The present study used functional magnetic resonance imaging to
      investigate emotion-specific amygdala activation in schizophrenia using a novel
      adaptive emotion recognition paradigm. Participants comprised 11 schizophrenia
      outpatients and 16 healthy controls who viewed face stimuli expressing emotions
      of anger, fear, happiness, and disgust, as well as neutral expressions. The
      adaptive emotion recognition approach allows the assessment of group differences
      in both emotion recognition performance and associated neuronal activity while
      also ensuring a comparable number of correctly recognized emotions between
      groups. Schizophrenia participants were slower and had a negative bias in emotion
      recognition. In addition, they showed reduced differential activation during
      recognition of emotional compared with neutral expressions. Correlation analyses
      revealed an association of a negative bias with amygdala activation for neutral
      facial expressions that was specific to the patient group. We replicated previous
      findings of affected emotion recognition in schizophrenia. Furthermore, we
      demonstrated that altered amygdala activation in the patient group was associated
      with the occurrence of a negative bias. These results provide further evidence
      for impaired social cognition in schizophrenia and point to a central role of the
      amygdala in negative misperceptions of facial stimuli in schizophrenia. 

PMID- 24434196
TI  - The effect of beta-glucan on formation and functionality of neutrophil
      extracellular traps in carp (Cyprinus carpio L.).
AB  - The formation of neutrophil extracellular traps (NETs) has been characterised as
      a novel antimicrobial host defence strategy of neutrophils besides phagocytosis
      and degranulation, which may lead to entrapment and subsequent immobilisation
      and/or killing of bacterial pathogens. Here we studied the effect of the feed
      additive beta-glucan, namely MacroGard((r)), on the formation and functionality
      of NETs in carp. Therefore, common carp (Cyprinus carpio) head kidney and kidney
      cells were isolated and treated with or without beta-glucan over time. The
      formation of NETs was analysed by immunofluorescence microscopy and revealed a
      distinct increase of NET-formation with beta-glucan. Furthermore the subsequent
      entrapment of Aeromonas hydrophila, an important fish pathogen, was increased
      after stimulating the cells with beta-glucan. However, beta-glucan did not lead
      to a stimulation of antimicrobial activity of neutrophils against A. hydrophila.
      In conclusion, the data underline the fact that the feed additive beta-glucan is
      able to modulate carp neutrophil functions.

PMID- 24434193
TI  - Brain atrophy in primary progressive aphasia involves the cholinergic basal
      forebrain and Ayala's nucleus.
AB  - Primary progressive aphasia (PPA) is characterized by left hemispheric
      frontotemporal cortical atrophy. Evidence from anatomical studies suggests that
      the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal
      forebrain, may be involved in the pathological process of PPA. Therefore, we
      studied the pattern of cortical and basal forebrain atrophy in 10 patients with a
      clinical diagnosis of PPA and 18 healthy age-matched controls using high
      resolution magnetic resonance imaging (MRI). We determined the cholinergic basal
      forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference
      space based on histological sections and the MRI scan of a post-mortem brain in
      cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in
      PPA patients compared with controls, including prefrontal, lateral temporal and
      medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in
      left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first
      time, we have described the pattern of basal forebrain atrophy in PPA and
      confirmed the involvement of NSP that had been predicted based on theoretical
      considerations. Our findings may enhance understanding of the role of cholinergic
      degeneration for the regional specificity of the cortical destruction leading to
      the syndrome of PPA.

PMID- 24434197
TI  - RNAi knock-down of shrimp Litopenaeus vannamei Toll gene and immune deficiency
      gene reveals their difference in regulating antimicrobial peptides transcription.
AB  - NF-kappaB dependent antimicrobial peptides (AMPs) are of critical importance in
      protecting insects or mammals from microorganisms infection. However, we still do
      not make clear signaling pathways in regulating AMPs expression in shrimps. In
      this study, RNAi approach was used to study differences between Toll signaling
      pathway and immune deficiency signaling pathway in regulating the transcription
      of NF-kappaB dependent AMPs post bacteria challenge. Results showed that the
      transcription level of anti-lipopolysaccharide factor was highly suppressed in
      Litopenaeus vannamei immune deficiency (LvIMD) silenced shrimps by gene specific
      dsRNA compared to Litopenaeus vannamei Toll (LvToll) silenced shrimps with or
      without Vibrio anguillarum and Micrococcus lysodeikticus challenge. Conversely
      the transcription level of penaeidin3a was significantly suppressed in LvToll
      silenced shrimps compared to LvIMD silenced shrimps. However, no obvious
      difference was found in regulating the transcription of CrustinP. Meanwhile, we
      found that silencing LvToll both down regulated the transcription of Dorsal and
      Relish while silencing LvIMD only down regulated the transcription of Relish. At
      last, shrimp survival experiment showed that post V. anguillarum challenge high
      mortality was found both in LvToll and LvIMD silenced groups while post M.
      lysodeikticus challenge we saw high mortality only in LvToll silenced group.
      Hence, we conclude that shrimp L. vannamei Toll pathway and IMD pathway might be
      different in regulating the transcription of NF-kappaB dependent AMPs and
      responding to bacteria challenge but not independent of each other.

PMID- 24434198
TI  - Feasibility testing of a web-based symptom self-management system for persons
      living with HIV.
AB  - The purpose of this study was to explore the feasibility of using a Web-based
      tool to provide tailored symptom management strategies for persons living with
      HIV (PLWH) and to estimate the effect size of the tool for future studies.
      Testing the components of the Web-based system was done by incorporating a
      repeated-measures design measuring the outcomes of symptom frequency and
      intensity, use of symptom management strategies, and engagement with health care
      providers. We recruited 42 PLWH; participants were enrolled in the study for 12
      weeks and were asked to use the system and complete the questionnaires every 2
      weeks. Our results showed that participants who used the strategies were more
      likely to have a decrease in symptom frequency and intensity. Findings from this
      feasibility study provide preliminary evidence for the use of a Web-based HIV
      symptom management tool with self-management strategies for individuals living
      with HIV infection.

PMID- 24434199
TI  - Identifications of household's spores using mid infrared spectroscopy.
AB  - Exposure to household fungi is very common both inside and outside the house and
      can cause health issues. The application of fourier transforms mid infrared
      spectroscopy (FTIR) as a screening technique for the detection and identification
      of household fungi was investigated. Early detection and identification of these
      household pathogens is very important and critical for their control. The current
      available methods for identification of fungi are time consuming, expensive and
      not very specific. Mid IR spectroscopy is a reliable and sensitive technique for
      the detection of spores. FTIR Spectra of four household fungi such as Aspergillus
      Ochraceus, Aspergillus Niger, Candida Glabrata and Penicillium Roguefortii were
      recorded in the mid infrared range from 600 to 4000cm(-1) using attenuated total
      reflectance (ATR) sampling accessory. Chemometrics analysis using principal
      component analysis (PCA), canonical variate analysis (CVA) and linear
      discriminant analysis (LDA) were performed to discriminate the fungi samples.
      Correspondence analysis (CA) was performed in order to visualize the relationship
      between different spores. An optimum classification of 100% was achieved for four
      different fungi. Results demonstrated that discriminant analysis of the FTIR
      spectra of fungi could be used for rapid detection of household fungi. 

PMID- 24434200
TI  - Charge-transfer interactions of metoclopramide nausea drug against six kind of pi
      acceptors: spectral and thermal discussions.
AB  - The target of this paper is aimed to discuss the fast and newly techniques in
      order to assessment the metoclopramide (Mcp) nausea drug in pure form in solid
      and solution shape with different kind of pi-acceptors upon charge transfer
      interactions. Charge-transfer complexes (CTC) of metoclopramide with picric acid
      (PA), 2,3-dichloro-5,6-dicyano-p-benzoquinon (DDQ), tetracyanoquinodimethane
      (TCNQ), m-dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA) and tetrachloro-p
      quinon (p-CL) have been studied spectrophotometrically in absolute methanol at
      room temperature. The stoichiometries of the complexes were found to be 1:1 ratio
      by the spectrophotometric titration between metoclopramide and represented pi
      acceptors. The equilibrium constants, molar extinction coefficient (epsilonCT)
      and spectroscopic-physical parameters (standard free energy (DeltaG degrees ),
      oscillator strength (f), transition dipole moment (MU), resonance energy (RN) and
      ionization potential (ID)) of the complexes were determined upon the modified
      Benesi-Hildebrand equation. The results indicate that the formation constants for
      the complexes depend on the nature of electron acceptors and configuration of
      drug donor, and also the spectral studies of the complexes were determined by
      (infrared, Raman, and (1)H NMR) spectra and X-ray powder diffraction (XRD). The
      charge-transfer complexes are formed during the interaction of electron-acceptors
      and electron-donors as result of partial or complete transfer of a negative
      charge from (D(+)-A(-)). 

PMID- 24434201
TI  - Phenylalanine and tyrosine methyl ester intramolecular interactions and
      conformational analysis by (1)H NMR and infrared spectroscopies and theoretical
      calculations.
AB  - Amino acid conformational analysis in solution are scarce, since these compounds
      present a bipolar zwitterionic structure ((+)H3NCHRCOO(-)) in these media. Also,
      intramolecular hydrogen bonds have been classified as the sole interactions
      governing amino acid conformational behavior in the literature. In the present
      work we propose phenylalanine and tyrosine methyl ester conformational studies in
      different solvents by (1)H NMR and infrared spectroscopies and theoretical
      calculations. Both experimental and theoretical results are in agreement and
      suggest that the conformational behavior of the phenylalanine and tyrosine methyl
      esters are similar and are dictated by the interplay between steric and
      hyperconjugative interactions. 

PMID- 24434202
TI  - Conjugation of a TLR7 agonist and antigen enhances protection in the S.
      pneumoniae murine infection model.
AB  - Next generation vaccine adjuvants include Toll like receptor agonists, which are
      mostly extracted from microorganisms, but synthetic small molecule TLR agonists
      have also been identified. However, their delivery systems have not been
      optimized for effective administration in conjunction with antigens. Here, we
      describe a novel approach in which a small molecule TLR agonist was directly
      conjugated to antigen to ensure effective co-delivery. We describe the
      conjugation of a recombinant protective antigen from Streptococcus pneumoniae
      linked to a TLR7 agonist. Following thorough characterization to ensure no
      aggregation, the conjugate was evaluated in a murine infection model. Results
      showed that the conjugate extended the animals' survival after lethal challenge
      with S. pneumoniae. Comparable results were obtained with a dose 10-fold lower
      than that of the native unconjugated antigen. Notably, the animals immunized with
      the same dose of unconjugated TLR7 agonist and antigen showed no adjuvant effect.
      The increased immunogenicity was likely a consequence of the co-localization of
      TLR7 agonist and antigen by chemical binding and was more effective than simple
      co-administration. This approach can be adopted to increase potency of a broad
      variety of antigens and reduce the dose of antigen required to induce protective
      immunity. 

PMID- 24434203
TI  - CARMA: CARM1 methylation of SWI/SNF in breast cancer.
AB  - In this issue of Cancer Cell, Wang and colleagues report that CARM1, a protein
      arginine methyltransferase, specifically methylates BAF155/SMARCC1, a core
      subunit of the SWI/SNF chromatin remodeling/tumor suppressor complex. This
      modification facilitates the targeting of BAF155 to genes of the c-Myc pathway
      and enhances breast cancer progression and metastasis. 

PMID- 24434204
TI  - RAS's cloak of invincibility slips at last?
AB  - KRAS is the most frequently activated oncogene in human cancer, but it has, so
      far, shrugged off all attempts to inhibit its function directly. However, a
      recent report provides an entirely new approach to blocking mutant KRAS with
      small molecules and has the added benefit of sparing the wild-type protein. 

PMID- 24434205
TI  - Unlocking new therapeutic targets and resistance mechanisms in mantle cell
      lymphoma.
AB  - Mantle cell lymphoma is an aggressive tumor for which new drugs targeting
      underlying molecular mechanisms are opening promising avenues. A recent study has
      elucidated the basis for targeting B cell receptor signaling in these lymphomas
      and identified somatic mutations in NF-kappaB regulatory genes that confer
      resistance to this therapy. 

PMID- 24434206
TI  - From anecdote to targeted therapy: the curious case of thalidomide in multiple
      myeloma.
AB  - Thalidomide and related drugs are key drugs for the treatment of multiple myeloma
      (MM). These agents bind to cereblon, a component of a ubiquitin ligase complex,
      altering the specificity of the complex to induce the ubiquitylation and
      degradation of Ikaros (IKZF1) and Aiolos (IKZF3), transcription factors essential
      for MM growth.

PMID- 24434207
TI  - Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis.
AB  - Why does cancer risk increase as we age? Frequently attributed to the multi-hit
      hypothesis and the time required to accumulate genomic mutations, this question
      is a matter of ongoing debate. Here, we propose that the normal decline in
      oxidative metabolism during aging constitutes an early and important "hit" that
      drives tumorigenesis. Central to these metabolic changes are the sirtuins, a
      family of NAD(+)-dependent deacylases that have evolved as coordinators of
      physiological responses to nutrient intake and energetic demand. Thus, the
      modulation of sirtuins might be a fruitful approach to reversing the age-related
      metabolic changes that could underlie tumorigenesis. 

PMID- 24434208
TI  - CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression
      and metastasis.
AB  - Coactivator-associated arginine methyltransferase 1 (CARM1), a coactivator for
      various cancer-relevant transcription factors, is overexpressed in breast cancer.
      To elucidate the functions of CARM1 in tumorigenesis, we knocked out CARM1 from
      several breast cancer cell lines using Zinc-Finger Nuclease technology, which
      resulted in drastic phenotypic and biochemical changes. The CARM1 KO cell lines
      enabled identification of CARM1 substrates, notably the SWI/SNF core subunit
      BAF155. Methylation of BAF155 at R1064 was found to be an independent prognostic
      biomarker for cancer recurrence and to regulate breast cancer cell migration and
      metastasis. Furthermore, CARM1-mediated BAF155 methylation affects gene
      expression by directing methylated BAF155 to unique chromatin regions (e.g., c
      Myc pathway genes). Collectively, our studies uncover a mechanism by which BAF155
      acquires tumorigenic functions via arginine methylation.

PMID- 24434210
TI  - The cyclin-like protein Spy1 regulates growth and division characteristics of the
      CD133+ population in human glioma.
AB  - The heterogeneity of brain cancers, as most solid tumors, complicates diagnosis
      and treatment. Identifying and targeting populations of cells driving
      tumorigenesis is a top priority for the cancer biology field. This is not a
      trivial task; considerable variance exists in the driving mutations, identifying
      markers, and evolutionary pressures influencing initiating cells in different
      individual tumors. Despite this, the ability to self-renew and differentiate must
      be conserved to reseed a heterogeneous tumor mass. Focusing on one example of a
      tumor-initiating cell population, we demonstrate that the atypical cyclin-like
      protein Spy1 plays a role in balancing the division properties of glioma cells
      with stemness properties. This mechanistic insight may provide new opportunities
      for therapeutic intervention of brain cancer.

PMID- 24434209
TI  - Targeting the tumor microenvironment with interferon-beta bridges innate and
      adaptive immune responses.
AB  - Antibodies (Abs) that preferentially target oncogenic receptors have been
      increasingly used for cancer therapy, but tumors often acquire intrinsic Ab
      resistance after prolonged and costly treatment. Herein we armed the Ab with
      IFNbeta and observed that it is more potent than the first generation of Ab for
      controlling Ab-resistant tumors. This strategy controls Ab resistance by
      rebridging suppressed innate and adaptive immunity in the tumor microenvironment.
      Mechanistically, Ab-IFNbeta therapy primarily and directly targets intratumoral
      dendritic cells, which reactivate CTL by increasing antigen cross-presentation
      within the tumor microenvironment. Additionally, blocking PD-L1, which is induced
      by Ab-IFNbeta treatment, overcomes treatment-acquired resistance and completely
      eradicates established tumors. This study establishes a next-generation Ab-based
      immunotherapy that targets and eradicates established Ab-resistant tumors.

PMID- 24434211
TI  - A targeting modality for destruction of RNA polymerase I that possesses
      anticancer activity.
AB  - We define the activity and mechanisms of action of a small molecule lead compound
      for cancer targeting. We show that the compound, BMH-21, has wide and potent
      antitumorigenic activity across NCI60 cancer cell lines and represses tumor
      growth in vivo. BMH-21 binds GC-rich sequences, which are present at a high
      frequency in ribosomal DNA genes, and potently and rapidly represses RNA
      polymerase I (Pol I) transcription. Strikingly, we find that BMH-21 causes
      proteasome-dependent destruction of RPA194, the large catalytic subunit protein
      of Pol I holocomplex, and this correlates with cancer cell killing. Our results
      show that Pol I activity is under proteasome-mediated control, which reveals an
      unexpected therapeutic opportunity.

PMID- 24434213
TI  - Vascular RhoJ is an effective and selective target for tumor angiogenesis and
      vascular disruption.
AB  - Current antiangiogenic therapy is limited by its cytostatic nature and systemic
      side effects. To address these limitations, we have unveiled the role of RhoJ, an
      endothelial-enriched Rho GTPase, during tumor progression. RhoJ blockade provides
      a double assault on tumor vessels by both inhibiting tumor angiogenesis and
      disrupting the preformed tumor vessels through the activation of the RhoA-ROCK
      (Rho kinase) signaling pathway in tumor endothelial cells, consequently resulting
      in a functional failure of tumor vasculatures. Moreover, enhanced anticancer
      effects were observed when RhoJ blockade was employed in concert with a cytotoxic
      chemotherapeutic agent, angiogenesis-inhibiting agent, or vascular-disrupting
      agent. These results identify RhoJ blockade as a selective and effective
      therapeutic strategy for targeting tumor vasculature with minimal side effects.

PMID- 24434215
TI  - SnapShot: diffuse large B cell lymphoma.

PMID- 24434212
TI  - Widespread genetic heterogeneity in multiple myeloma: implications for targeted
      therapy.
AB  - We performed massively parallel sequencing of paired tumor/normal samples from
      203 multiple myeloma (MM) patients and identified significantly mutated genes and
      copy number alterations and discovered putative tumor suppressor genes by
      determining homozygous deletions and loss of heterozygosity. We observed frequent
      mutations in KRAS (particularly in previously treated patients), NRAS, BRAF,
      FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often
      present in subclonal populations, and multiple mutations within the same pathway
      (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling
      predicts only partial treatment efficacy of targeting subclonal mutations, and
      even growth promotion of nonmutated subclones in some cases. These results
      emphasize the importance of heterogeneity analysis for treatment decisions.

PMID- 24434214
TI  - Cbx4 governs HIF-1alpha to potentiate angiogenesis of hepatocellular carcinoma by
      its SUMO E3 ligase activity.
AB  - Cbx4 is a polycomb group protein that is also a SUMO E3 ligase, but its potential
      roles in tumorigenesis remain to be explored. Here, we report that Cbx4, but not
      other members of the Cbx family, enhances hypoxia-induced vascular endothelial
      growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma
      (HCC) cells through enhancing HIF-1alpha sumoylations at K391 and K477 in its two
      SUMO-interacting motifs-dependent mechanisms and increasing transcriptional
      activity of HIF-1. The Cbx4 expression is significantly correlated with VEGF
      expression, angiogenesis, and the overall survival of HCC patients and also in
      subcutaneously and orthotopically transplanted mice HCC models. Collectively, our
      findings demonstrate that Cbx4 plays a critical role in tumor angiogenesis by
      governing HIF-1alpha protein.

PMID- 24434216
TI  - A modular degree-of-interest specification for the visual analysis of large
      dynamic networks.
AB  - Large dynamic networks are targets of analysis in many fields. Tracking temporal
      changes at scale in these networks is challenging due in part to the fact that
      small changes can be missed or drowned-out by the rest of the network. For static
      networks, current approaches allow the identification of specific network
      elements within their context. However, in the case of dynamic networks, the user
      is left alone with finding salient local network elements and tracking them over
      time. In this work, we introduce a modular DoI specification to flexibly define
      what salient changes are and to assign them a measure of their importance in a
      time-varying setting. The specification takes into account neighborhood structure
      information, numerical attributes of nodes/edges, and their temporal evolution. A
      tailored visualization of the DoI specification complements our approach.
      Alongside a traditional node-link view of the dynamic network, it serves as an
      interface for the interactive definition of a DoI function. By using it to
      successively refine and investigate the captured details, it supports the
      analysis of dynamic networks from an initial view until pinpointing a user's
      analysis goal. We report on applying our approach to scientific coauthorship
      networks and give concrete results for the DBLP data set. 

PMID- 24434217
TI  - A structure-based distance metric for high-dimensional space exploration with
      multidimensional scaling.
AB  - Although the euclidean distance does well in measuring data distances within high
      dimensional clusters, it does poorly when it comes to gauging intercluster
      distances. This significantly impacts the quality of global, low-dimensional
      space embedding procedures such as the popular multidimensional scaling (MDS)
      where one can often observe nonintuitive layouts. We were inspired by the
      perceptual processes evoked in the method of parallel coordinates which enables
      users to visually aggregate the data by the patterns the polylines exhibit across
      the dimension axes. We call the path of such a polyline its structure and suggest
      a metric that captures this structure directly in high-dimensional space. This
      allows us to better gauge the distances of spatially distant data constellations
      and so achieve data aggregations in MDS plots that are more cognizant of existing
      high-dimensional structure similarities. Our biscale framework distinguishes far
      distances from near-distances. The coarser scale uses the structural similarity
      metric to separate data aggregates obtained by prior classification or
      clustering, while the finer scale employs the appropriate euclidean distance. 

PMID- 24434218
TI  - A task taxonomy for network evolution analysis.
AB  - Visualization has proven to be a useful tool for understanding network
      structures. Yet the dynamic nature of social media networks requires powerful
      visualization techniques that go beyond static network diagrams. To provide
      strong temporal network visualization tools, designers need to understand what
      tasks the users have to accomplish. This paper describes a taxonomy of temporal
      network visualization tasks. We identify the 1) entities, 2) properties, and 3)
      temporal features, which were extracted by surveying 53 existing temporal network
      visualization systems. By building and examining the task taxonomy, we report
      which tasks are well covered by existing systems and make suggestions for
      designing future visualization tools. The feedback from 12 network analysts
      helped refine the taxonomy. 

PMID- 24434219
TI  - Activity detection in scientific visualization.
AB  - For large-scale simulations, the data sets are so massive that it is sometimes
      not feasible to view the data with basic visualization methods, let alone explore
      all time steps in detail. Automated tools are necessary for knowledge discovery,
      i.e., to help sift through the data and isolate specific time steps that can then
      be further explored. Scientists study patterns and interactions and want to know
      when and where interesting things happen. Activity detection, the detection of
      specific interactions of objects which span a limited duration of time, has been
      an active research area in the computer vision community. In this paper, we
      introduce activity detection to scientific simulations and show how it can be
      utilized in scientific visualization. We show how activity detection allows a
      scientist to model an activity and can then validate their hypothesis on the
      underlying processes. Three case studies are presented. 

PMID- 24434220
TI  - An evaluation of depth enhancing perceptual cues for vascular volume
      visualization in neurosurgery.
AB  - Cerebral vascular images obtained through angiography are used by neurosurgeons
      for diagnosis, surgical planning, and intraoperative guidance. The intricate
      branching of the vessels and furcations, however, make the task of understanding
      the spatial three-dimensional layout of these images challenging. In this paper,
      we present empirical studies on the effect of different perceptual cues (fog,
      pseudo-chromadepth, kinetic depth, and depicting edges) both individually and in
      combination on the depth perception of cerebral vascular volumes and compare
      these to the cue of stereopsis. Two experiments with novices and one experiment
      with experts were performed. The results with novices showed that the pseudo
      chromadepth and fog cues were stronger cues than that of stereopsis. Furthermore,
      the addition of the stereopsis cue to the other cues did not improve relative
      depth perception in cerebral vascular volumes. In contrast to novices, the
      experts also performed well with the edge cue. In terms of both novice and expert
      subjects, pseudo-chromadepth and fog allow for the best relative depth
      perception. By using such cues to improve depth perception of cerebral
      vasculature, we may improve diagnosis, surgical planning, and intraoperative
      guidance. 

PMID- 24434221
TI  - Attributes of subtle cues for facilitating visual search in augmented reality.
AB  - Goal-oriented visual search is performed when a person intentionally seeks a
      target in the visual environment. In augmented reality (AR) environments, visual
      search can be facilitated by augmenting virtual cues in the person's field of
      view. Traditional use of explicit AR cues can potentially degrade visual search
      performance due to the creation of distortions in the scene. An alternative to
      explicit cueing, known as subtle cueing, has been proposed as a clutter-neutral
      method to enhance visual search in video-see-through AR. However, the effects of
      subtle cueing are still not well understood, and more research is required to
      determine the optimal methods of applying subtle cueing in AR. We performed two
      experiments to investigate the variables of scene clutter, subtle cue opacity,
      size, and shape on visual search performance. We introduce a novel method of
      experimentally manipulating the scene clutter variable in a natural scene while
      controlling for other variables. The findings provide supporting evidence for the
      subtlety of the cue, and show that the clutter conditions of the scene can be
      used both as a global classifier, as well as a local performance measure. 

PMID- 24434222
TI  - FaceWarehouse: a 3D facial expression database for visual computing.
AB  - We present FaceWarehouse, a database of 3D facial expressions for visual
      computing applications. We use Kinect, an off-the-shelf RGBD camera, to capture
      150 individuals aged 7-80 from various ethnic backgrounds. For each person, we
      captured the RGBD data of her different expressions, including the neutral
      expression and 19 other expressions such as mouth-opening, smile, kiss, etc. For
      every RGBD raw data record, a set of facial feature points on the color image
      such as eye corners, mouth contour, and the nose tip are automatically localized,
      and manually adjusted if better accuracy is required. We then deform a template
      facial mesh to fit the depth data as closely as possible while matching the
      feature points on the color image to their corresponding points on the mesh.
      Starting from these fitted face meshes, we construct a set of individual-specific
      expression blendshapes for each person. These meshes with consistent topology are
      assembled as a rank-3 tensor to build a bilinear face model with two attributes:
      identity and expression. Compared with previous 3D facial databases, for every
      person in our database, there is a much richer matching collection of
      expressions, enabling depiction of most human facial actions. We demonstrate the
      potential of FaceWarehouse for visual computing with four applications: facial
      image manipulation, face component transfer, real-time performance-based facial
      image animation, and facial animation retargeting from video to image. 

PMID- 24434223
TI  - Implicit incompressible SPH.
AB  - We propose a novel formulation of the projection method for Smoothed Particle
      Hydrodynamics (SPH). We combine a symmetric SPH pressure force and an SPH
      discretization of the continuity equation to obtain a discretized form of the
      pressure Poisson equation (PPE). In contrast to previous projection schemes, our
      system does consider the actual computation of the pressure force. This
      incorporation improves the convergence rate of the solver. Furthermore, we
      propose to compute the density deviation based on velocities instead of positions
      as this formulation improves the robustness of the time-integration scheme. We
      show that our novel formulation outperforms previous projection schemes and state
      of-the-art SPH methods. Large time steps and small density deviations of down to
      0.01 percent can be handled in typical scenarios. The practical relevance of the
      approach is illustrated by scenarios with up to 40 million SPH particles. 

PMID- 24434224
TI  - Optimized synthesis of art patterns and layered textures.
AB  - Line drawings and digital arts appear everywhere, from simple icons and logos to
      cartoons, maps, and illustrations. We define art patterns as the subset of line
      drawings and digital arts that are comprised of repeated elements. There exist
      textures that share characteristics with art patterns. Examples of such textures
      include piled discrete elements with curved contours. Inspired by recent success
      of exemplar-based texture synthesis, in this paper, we focus on synthesizing art
      patterns and textures with curvilinear features from exemplars, which we cast as
      a global optimization problem. Our energy function for this problem measures both
      the appearance similarity of color patterns and shape similarity of curvilinear
      features between an input exemplar and a synthesized image. We develop an overall
      expectation-maximization-style algorithm for minimizing this energy function. The
      shape similarity part of the energy is minimized through an innovative
      application of the level set method. We further generalize our energy function
      and optimization algorithm to multilayer pattern and texture synthesis. Our
      generalized optimization can effectively handle multiple layers and synthesize
      valid instances of interaction. 

PMID- 24434225
TI  - Scalable collision detection using p-partition fronts on many-core processors.
AB  - We present a new parallel algorithm for collision detection using many-core
      computing platforms of CPUs or GPUs. Based on the notion of a $(p)$-partition
      front, our algorithm is able to evenly partition and distribute the workload of
      BVH traversal among multiple processing cores without the need for dynamic
      balancing, while minimizing the memory overhead inherent to the state-of-the-art
      parallel collision detection algorithms. We demonstrate the scalability of our
      algorithm on different benchmarking scenarios with and without using temporal
      coherence, including dynamic simulation of rigid bodies, cloth simulation, and
      random collision courses. In these experiments, we observe nearly linear
      performance improvement in terms of the number of processing cores on the CPUs
      and GPUs. 

PMID- 24434226
TI  - Similarity preserving snippet-based visualization of web search results.
AB  - Internet users are very familiar with the results of a search query displayed as
      a ranked list of snippets. Each textual snippet shows a content summary of the
      referred document (or webpage) and a link to it. This display has many
      advantages, for example, it affords easy navigation and is straightforward to
      interpret. Nonetheless, any user of search engines could possibly report some
      experience of disappointment with this metaphor. Indeed, it has limitations in
      particular situations, as it fails to provide an overview of the document
      collection retrieved. Moreover, depending on the nature of the query--for
      example, it may be too general, or ambiguous, or ill expressed--the desired
      information may be poorly ranked, or results may contemplate varied topics.
      Several search tasks would be easier if users were shown an overview of the
      returned documents, organized so as to reflect how related they are, content
      wise. We propose a visualization technique to display the results of web queries
      aimed at overcoming such limitations. It combines the neighborhood preservation
      capability of multidimensional projections with the familiar snippet-based
      representation by employing a multidimensional projection to derive two
      dimensional layouts of the query search results that preserve text similarity
      relations, or neighborhoods. Similarity is computed by applying the cosine
      similarity over a "bag-of-words" vector representation of collection built from
      the snippets. If the snippets are displayed directly according to the derived
      layout, they will overlap considerably, producing a poor visualization. We
      overcome this problem by defining an energy functional that considers both the
      overlapping among snippets and the preservation of the neighborhood structure as
      given in the projected layout. Minimizing this energy functional provides a
      neighborhood preserving two-dimensional arrangement of the textual snippets with
      minimum overlap. The resulting visualization conveys both a global view of the
      query results and visual groupings that reflect related results, as illustrated
      in several examples shown.

PMID- 24434227
TI  - T-ReX: interactive global illumination of massive models on heterogeneous
      computing resources.
AB  - We propose several interactive global illumination techniques for a diverse set
      of massive models. We integrate these techniques within a progressive rendering
      framework that aims to achieve both a high rendering throughput and an
      interactive responsiveness. To achieve a high rendering throughput, we utilize
      heterogeneous computing resources consisting of CPU and GPU. To reduce expensive
      data transmission costs between CPU and GPU, we propose to use separate,
      decoupled data representations dedicated for each CPU and GPU. Our
      representations consist of geometric and volumetric parts, provide different
      levels of resolutions, and support progressive global illumination for massive
      models. We also propose a novel, augmented volumetric representation that
      provides additional geometric resolutions within our volumetric representation.
      In addition, we employ tile-based rendering and propose a tile ordering technique
      considering visual perception. We have tested our approach with a diverse set of
      large-scale models including CAD, scanned, simulation models that consist of more
      than 300 million triangles. By using our methods, we are able to achieve ray
      processing performances of 3 M~20 M rays per second, while limiting response time
      to users within 15~67 ms. We also allow dynamic modifications of light, and
      interactive setting of materials, while efficiently supporting novel view
      rendering.

PMID- 24434228
TI  - Yttrium-90 radioembolization of liver tumors: what do the images tell us?
AB  - Transarterial radioembolization (TARE) with yttrium 90 microspheres is an
      increasingly popular therapy for both primary and secondary liver malignancies.
      TARE entails delivery of beta-particle brachytherapy and embolization of the
      tumor vasculature. The consequent biological sequelae are distinct from those of
      other transarterial therapies for liver tumors, as reflected in the often
      baffling post-treatment imaging features. As the clinical use of TARE is
      increasing, more diverse post-treatment radiological findings are encountered
      with variable overlap among treatment response, residual disease, reactionary
      changes and complications. Thus, post-TARE image interpretation is challenging.
      This review provides a comprehensive description of the different findings seen
      in post-treatment scans, with the aim of facilitating appropriate radiological
      interpretation of post-TARE pathologic changes, notwithstanding their existing
      limitations. 

PMID- 24434229
TI  - Outreach and integration programs to promote family planning in the extended
      postpartum period.
AB  - BACKGROUND: WHO recommends birth spacing to improve the health of the mother and
      child. One strategy to facilitate birth spacing is to improve the use of family
      planning during the first year postpartum. OBJECTIVES: To determine from the
      literature the effectiveness of postpartum family-planning programs and to
      identify research gaps. SEARCH STRATEGY: PubMed and the Cochrane Central Register
      of Controlled Trials were systematically searched for articles published between
      database inception and March 2013. Abstracts of conference presentations,
      dissertations, and unpublished studies were also considered. SELECTION CRITERIA:
      Published studies with birth spacing or contraceptive use outcomes were included.
      DATA COLLECTION AND ANALYSIS: Standard abstract forms and the US Preventive
      Services Task Force grading system were used to summarize and assess the quality
      of the evidence. MAIN RESULTS: Thirty-four studies were included. Prenatal care,
      home visitation programs, and educational interventions were associated with
      improved family-planning outcomes, but should be further studied in low-resource
      settings. Mother-infant care integration, multidisciplinary interventions, and
      cash transfer/microfinance interventions need further investigation. CONCLUSIONS:
      Programmatic interventions may improve birth spacing and contraceptive uptake.
      Larger well-designed studies in international settings are needed to determine
      the most effective ways to deliver family-planning interventions.

PMID- 24434230
TI  - Prevalence of polycystic ovary syndrome among fertile and infertile women in
      Minia Governorate, Egypt.

PMID- 24434231
TI  - Prenatal diagnosis of Prader-Willi syndrome and Angelman syndrome for fetuses
      with suspicious deletion of chromosomal region 15q11-q13.
AB  - OBJECTIVE: To identify Prader-Willi syndrome (PWS) and Angelman syndrome (AS)
      among fetuses with suspicious deletion of the chromosomal region 15q11-q13.
      METHODS: In a retrospective study, data were assessed from fetuses missing
      chromosomal band 15q12 that underwent molecular diagnosis at the National Chen
      Kung University Hospital, Tainan, Taiwan, between January 2001 and December 2012.
      Amniocytes were subjected to molecular testing, including fluorescence in situ
      hybridization (FISH) analysis, methylation-specific PCR (M-PCR), and methylation
      specific multiplex-ligation-dependent probe amplification (MS-MLPA). RESULTS:
      During the 12-year study period, 26 041 amniocyte samples were analyzed at the
      study center and 27 (0.1%) were found to have a missing 15q12 band. A further 16
      samples with a missing 15q12 band were received from other cytogenetic
      laboratories; as a result, 43 amniocyte samples lacking chromosomal band 15q12
      underwent further molecular testing. Among these samples, 3 fetuses (7.0%) were
      found to have PWS (n=1) or AS (n=2). CONCLUSION: A minority of cases with missing
      15q12 had deletion of the PWS/AS critical region. This finding draws attention to
      the subtle structural rearrangements that occur on 15q11-q13 and provides useful
      information for prenatal diagnosis of PWS and AS.

PMID- 24434232
TI  - Pure natural orifice transluminal endoscopic surgery (NOTES) involving peroral
      endoscopic salpingo-oophorectomy (POESY).
AB  - OBJECTIVE: Natural orifice transluminal endoscopic surgery (NOTES) is a surgical
      approach that uses natural orifices to gain access to areas of the body. In the
      present article, we describe the first transgastric pure NOTES salpingo
      oophorectomy, which we call peroral endoscopic salpingo-oophorectomy (POESY).
      METHODS: A woman with BRCA1 mutation presented for prophylactic bilateral
      salpingo-oophorectomy. We offered her the transgastric approach, having performed
      more than 25 transgastric appendectomies. After gastroscopic incision in the
      corpus wall, we advanced the gastroscope into the abdominal cavity. Salpingo
      oophorectomy was performed with the help of an intrauterine manipulator and a
      transvaginally introduced 5-mm trocar. The posterior colpotomy was dilated and
      the specimens were extracted. The gastrotomy was closed with an over-the-scope
      clip, and the colpotomy with a running suture. RESULTS: The gastroscope provided
      excellent optical control and good tissue preparation. Prophylactic bilateral
      salpingo-oophorectomy was performed successfully via POESY. The patient recovered
      quickly and was discharged on the third day, with an uneventful follow-up.
      CONCLUSION: The present case demonstrates the feasibility of transgastric access.
      The gastroscope provided excellent optical control and good tissue preparation.
      Therefore, we expect an increasing role of transgastric procedures for diseases
      in the pelvic region, particularly if new endoscopic platforms with better means
      of instrumentation and tissue management become available.

PMID- 24434233
TI  - A relatively high number of pregnant women in Kuwait remain susceptible to
      rubella: a need for an alternative vaccination policy.
AB  - OBJECTIVE: To measure the prevalence of anti-rubella IgG and hepatitis B surface
      antigen (HBsAg) among pregnant women in Kuwait in order to assess the
      effectiveness of the current vaccination programs. SUBJECTS AND METHODS: This
      retrospective study involved 4,062 pregnant women evaluated in health centers in
      the Hawalli Province of Kuwait. They were screened for anti-rubella IgG and HBsAg
      using commercially available assays. The data were obtained from medical
      laboratory records. RESULTS: The mean age of the pregnant women was 29.2 +/- 5.26
      years (range 17-49). The rubella IgG prevalence among the pregnant women was
      88.4% (n = 3,589); 276 (6.8%) of the pregnant women had no antibody to rubella,
      and 197 (4.8%) had rubella antibody levels <=10 IU/ml. Therefore, 473 (11.6%) of
      the pregnant women were susceptible to rubella. The proportion of susceptible
      women increased with increasing age from 3.4 to 10.3% and from 3.4 to 6.7% among
      women aged <20 years and those aged >=40 years, respectively (p = 0.016). The
      prevalence of HBsAg was 0.3%, and it did not vary with age. CONCLUSION: The
      prevalence of both anti-rubella IgG and HBsAg among pregnant women in Kuwait was
      relatively high. However, about 11.6% of pregnant women in Kuwait remain
      susceptible to rubella infection and hence congenital infection and fetal
      malformation.

PMID- 24434234
TI  - Mismatch or cumulative stress: the pathway to depression is conditional on
      attention style.
AB  - In the study reported here, the main question we investigated was whether
      attention style could be a conditional adaptation. We organized participants of
      the TRacking Adolescents' Individual Lives Survey (TRAILS; N = 2,230) into
      shifters, sustainers, and two comparison groups, depending on their performance
      on a shifting- and a sustained-attention task at age 11 years. Compared with
      sustainers, shifters reported more pre- and perinatal risk factors and more
      childhood stress, and they adopted a faster life-history strategy. These
      differences were not found between the comparison groups, who performed well or
      poorly on both tasks, which suggests that specialization for either sustained or
      shifting attention is the key to conditional adaptation. In a subsample (n =
      860), we found that stress did not increase depression risk in shifters, whereas
      a mismatch between early and recent stress predicted depression in sustainers.
      Cumulative stress predicted depression in the comparison group. These results
      suggest that shifters retain high levels of plasticity throughout life, whereas
      sustainers' adapted their phenotype early in life to the expected mature
      environment.

PMID- 24434235
TI  - "That's not just beautiful--that's incredibly beautiful!": the adverse impact of
      inflated praise on children with low self-esteem.
AB  - In current Western society, children are often lavished with inflated praise
      (e.g., "You made an incredibly beautiful drawing!"). Inflated praise is often
      given in an attempt to raise children's self-esteem. An experiment (Study 1) and
      naturalistic study (Study 2) found that adults are especially inclined to give
      inflated praise to children with low self-esteem. This inclination may backfire,
      however. Inflated praise might convey to children that they should continue to
      meet very high standards-a message that might discourage children with low self
      esteem from taking on challenges. Another experiment (Study 3) found that
      inflated praise decreases challenge seeking in children with low self-esteem and
      has the opposite effect on children with high self-esteem. These findings show
      that inflated praise, although well intended, may cause children with low self
      esteem to avoid crucial learning experiences. 

PMID- 24434236
TI  - A lack of material resources causes harsher moral judgments.
AB  - In the research presented here, we tested the idea that a lack of material
      resources (e.g., low income) causes people to make harsher moral judgments
      because a lack of material resources is associated with a lower ability to cope
      with the effects of others' harmful behavior. Consistent with this idea, results
      from a large cross-cultural survey (Study 1) showed that both a chronic (due to
      low income) and a situational (due to inflation) lack of material resources were
      associated with harsher moral judgments. The effect of inflation was stronger for
      low-income individuals, whom inflation renders relatively more vulnerable. In a
      follow-up experiment (Study 2), we manipulated whether participants perceived
      themselves as lacking material resources by employing different anchors on the
      scale they used to report their income. The manipulation led participants in the
      material-resources-lacking condition to make harsher judgments of harmful, but
      not of nonharmful, transgressions, and this effect was explained by a sense of
      vulnerability. Alternative explanations were excluded. These results demonstrate
      a functional and contextually situated nature of moral psychology. 

PMID- 24434237
TI  - The attentional blink reveals the probabilistic nature of discrete conscious
      perception.
AB  - Attention and awareness are two tightly coupled processes that have been the
      subject of the same enduring debate: Are they allocated in a discrete or in a
      graded fashion? Using the attentional blink paradigm and mixture-modeling
      analysis, we show that awareness arises at central stages of information
      processing in an all-or-none manner. Manipulating the temporal delay between two
      targets affected subjects' likelihood of consciously perceiving the second
      target, but did not affect the precision of its representation. Furthermore,
      these results held across stimulus categories and paradigms, and they were
      dependent on attention having been allocated to the first target. The findings
      distinguish the fundamental contributions of attention and awareness at central
      stages of visual cognition: Conscious perception emerges in a quantal manner,
      with attention serving to modulate the probability that representations reach
      awareness. 

PMID- 24434238
TI  - Cognitive skills, student achievement tests, and schools.
AB  - Cognitive skills predict academic performance, so schools that improve academic
      performance might also improve cognitive skills. To investigate the impact
      schools have on both academic performance and cognitive skills, we related
      standardized achievement-test scores to measures of cognitive skills in a large
      sample (N = 1,367) of eighth-grade students attending traditional, exam, and
      charter public schools. Test scores and gains in test scores over time correlated
      with measures of cognitive skills. Despite wide variation in test scores across
      schools, differences in cognitive skills across schools were negligible after we
      controlled for fourth-grade test scores. Random offers of enrollment to
      oversubscribed charter schools resulted in positive impacts of such school
      attendance on math achievement but had no impact on cognitive skills. These
      findings suggest that schools that improve standardized achievement-test scores
      do so primarily through channels other than improving cognitive skills. 

PMID- 24434239
TI  - Neighborhood ethnic diversity and trust: the role of intergroup contact and
      perceived threat.
AB  - This research reported here speaks to a contentious debate concerning the
      potential negative consequences of diversity for trust. We tested the
      relationship between neighborhood diversity and out-group, in-group, and
      neighborhood trust, taking into consideration previously untested indirect
      effects via intergroup contact and perceived intergroup threat. A large-scale
      national survey in England sampled White British majority (N = 868) and ethnic
      minority (N = 798) respondents from neighborhoods of varying degrees of
      diversity. Multilevel path analyses showed some negative direct effects of
      diversity for the majority group but also confirmed predictions that diversity
      was associated indirectly with increased trust via positive contact and lower
      threat. These indirect effects had positive implications for total effects of
      diversity, cancelling out most negative direct effects. Our findings have
      relevance for a growing body of research seeking to disentangle effects of
      diversity on trust that has so far largely ignored the key role of intergroup
      contact. 

PMID- 24434240
TI  - Hepatitis E: an emerging disease.
AB  - Currently, the infection with the hepatitis E virus represents the most frequent
      cause for acute hepatitis and jaundice in the world. According to WHO
      estimations, around two billion people, representing one third of the world's
      population, live in endemic areas for HEV and, therefore, are at risk of
      infection. In developed countries, the circulation of the virus in both human and
      animal (swine, boar, deer) sewage has been confirmed; however, the incidence rate
      is low compared to that of developing countries where outbreaks of acute
      hepatitis transmitted via the fecal-oral route are originated, more frequently in
      the flooding season or after natural disasters, combined with deficient sanitary
      conditions. There are currently 4 known genotypes of HEV. Genotypes 1 and 2 are
      isolated in all human epidemic outbreaks in developing countries, while genotypes
      3 and 4 are isolated not only in humans but also in animals, in both developing
      and industrialized countries. These data support genotypes 3 and 4 having
      zoonotic nature. The diagnosis of this disease is based in the detection of anti
      HEV IgG and IgM in blood serum using enzyme-linked immunosorbent methods.
      However, the method that best confirms the diagnosis is the RT-PCR, which detects
      HEV RNA in blood serum and also provides the genotype. The clinical course is
      generally that of an acute hepatitis which in some cases may require
      hospitalization and that, in transplant patients or HIV infected individuals can
      become a chronic hepatitis. Furthermore, the virus constitutes an important risk
      for pregnant women. The hepatitis E can present a wide range of symptoms, from a
      subclinical case to chronic liver disease with extrahepatic manifestations. For
      this reason, the diagnostic is challenging if no differential diagnosis is
      included. There is no specific antiviral drug for hepatitis E, but satisfactory
      results have been observed in some patients treated with pegylated interferon
      alfa2a and/or ribavirin. This revision is an update of all the molecular,
      epidemiological, clinic and preventive knowledge on this emergent disease up to
      date. 

PMID- 24434241
TI  - A rare non-Robertsonian translocation with chromosome fusion
      der(5;15)(q35.3;q10): segregation analysis in male meiosis and preimplantation
      embryos.
AB  - Balanced chromosomal translocations do not normally have phenotypic
      manifestation, but lead to increased risk of infertility, miscarriage and live
      birth of chromosomally unbalanced offspring in carriers. The risk assessment of
      such outcomes in carriers of rare chromosomal abnormalities is complicated since
      limited information is available on the frequencies of unbalanced sperm and
      embryo formation. Therefore, the aim of this study was to investigate the amount
      of normal/balanced and unbalanced sperm and embryos of a rare non-Robertsonian
      chromosome fusion carrier with karyotype 45,XY,der(5;15)(q35.3;q10). Cytogenetic
      analyses of peripheral blood lymphocytes, multicolour fluorescence in situ
      hybridization on sperm sample, trophectoderm biopsy, and preimplantation genetic
      diagnosis by array comparative genomic hybridization were performed. The most
      frequent type of meiotic segregation was alternate (53% in sperm and 66.7% in
      embryos), followed by adjacent (44% in sperm and 33.3% in day-5 embryos).
      Additionally, 3:0 segregation was detected in sperm with a frequency of 2.6% and
      not detected in day-5 embryos. Results of sperm segregation analysis in rare
      rearrangement carriers are valuable for genetic counselling in assisted
      reproduction.

PMID- 24434242
TI  - Different topological organization of human brain functional networks with eyes
      open versus eyes closed.
AB  - Opening and closing the eyes are fundamental behaviors for directing attention to
      the external versus internal world. However, it remains unclear whether the
      states of eyes-open (EO) relative to eyes-closed (EC) are associated with
      different topological organizations of functional neural networks for
      exteroceptive and interoceptive processing (processing the external world and
      internal state, respectively). Here, we used resting-state functional magnetic
      resonance imaging and neural network analysis to investigate the topological
      properties of functional networks of the human brain when the eyes were open
      versus closed. The brain networks exhibited higher cliquishness and local
      efficiency, but lower global efficiency during the EO state compared to the EC
      state. These properties suggest an increase in specialized information processing
      along with a decrease in integrated information processing in EO (vs. EC). More
      importantly, the "exteroceptive" network, including the attentional system (e.g.,
      superior parietal gyrus and inferior parietal lobule), ocular motor system (e.g.,
      precentral gyrus and superior frontal gyrus), and arousal system (e.g., insula
      and thalamus), showed higher regional nodal properties (nodal degree, efficiency
      and betweenness centrality) in EO relative to EC. In contrast, the
      "interoceptive" network, composed of visual system (e.g., lingual gyrus, fusiform
      gyrus and cuneus), auditory system (e.g., Heschl's gyurs), somatosensory system
      (e.g., postcentral gyrus), and part of the default mode network (e.g., angular
      gyrus and anterior cingulate gyrus), showed significantly higher regional
      properties in EC vs. EO. In addition, the connections across sensory modalities
      were altered by volitional eye opening. The synchronicity between the visual
      system and the motor, somatosensory and auditory systems, characteristic of EC,
      was attenuated in EO. Further, the connections between the visual system and the
      attention, arousal and subcortical systems were increased in EO. These results
      may indicate that EO leads to a suppression of sensory modalities (other than
      visual) to allocate resources to exteroceptive processing. Our findings suggest
      that the topological organization of human brain networks dynamically switches
      corresponding to the information processing modes as we open or close our eyes. 

PMID- 24434243
TI  - Stem cells and kidney regeneration.
AB  - Kidney disease is an escalating burden all over the world. In addition to
      preventing kidney injury, regenerating damaged renal tissue is as important as to
      retard the progression of chronic kidney disease to end stage renal disease.
      Although the kidney is a delicate organ and has only limited regenerative
      capacity compared to the other organs, an increasing understanding of renal
      development and renal reprogramming has kindled the prospects of regenerative
      options for kidney disease. Here, we will review the advances in the kidney
      regeneration including the manipulation of renal tubular cells, fibroblasts,
      endothelial cells, and macrophages in renal disease. Several types of stem cells,
      such as bone marrow-derived cells, adipocyte-derived mesenchymal stem cells,
      embryonic stem cells, and induced pluripotent stem cells are also applied for
      renal regeneration. Endogenous or lineage reprogrammed renal progenitor cells
      represent an attractive possibility for differentiation into multiple renal cell
      types. Angiogenesis can ameliorate hypoxia and renal fibrosis. Based on these
      studies and knowledge, we hope to innovate more reliable pharmacological or
      biotechnical methods for kidney regeneration medicine. 

PMID- 24434244
TI  - Assessing quality of life in Taiwanese patients with Graves' ophthalmopathy.
AB  - BACKGROUND/PURPOSE: This study investigated the clinical significance of quality
      of life (QOL) related specifically to Graves' ophthalmopathy (GO) among Taiwanese
      patients. METHODS: We recruited 271 patients with GO who were seen at the
      National Taiwan University Hospital Department of Ophthalmology from September 1,
      2012 to November 30, 2012. Patients completed the GO-QOL Questionnaire. The main
      outcome measures were the scores on two GO-QOL subscales: visual functioning and
      appearance. The percentage of responses occurring at the maximum and minimum
      values was also calculated to assess possible ceiling and floor effects,
      respectively. RESULTS: The mean +/- standard deviation QOL scores for the
      subscales of visual functioning and appearance were 58.39 +/- 25.17 and 54.45 +/-
      20.52, respectively. The scores for both subscales were significantly correlated
      with disease severity and clinical activity scores (all p < 0.05). The QOL scores
      for the appearance subscale were significantly correlated with the degree of
      diplopia (p < 0.05). No significant ceiling or floor effects were observed for
      either subscale of the GO-QOL. CONCLUSION: Scores on the Chinese (Taiwan) version
      of the GO-QOL were strongly correlated with disease severity and clinical
      activity. The GO-QOL is a simple and practical tool that can be used to evaluate
      health-related QOL in GO patients.

PMID- 24434245
TI  - Role of PI3K/Akt/mTOR and MEK/ERK pathway in Concanavalin A induced autophagy in
      HeLa cells.
AB  - Concanavalin A (Con A), a mannose or glucose specific legume lectin, is well
      known for its anti-proliferative and cytotoxic effect on different types of
      cancer cells, through its binding to the membrane receptors leading to a major
      stimulus for the induction of distinct metabolic responses. Recently it has been
      also been proved that, Con A induces autophagy in hepatoma cells through
      internalization and mitochondria mediated pathway involving a mitochondrial
      interacting protein named Bcl2/E1B-19kDa protein-interacting protein 3 (BNIP3).
      Through this current endeavor, we propose a membrane associated pathway involved
      in Con A induced autophagy, taking Human cervical cancer (HeLa) cell as a cancer
      model. Here, we deciphered the role of membrane mediated phosphatidylinositol 3
      kinase (PI3K)/Akt/mTOR (mammalian target of rapamycin) and MEK/Extracellular
      signal-regulated kinases (ERK) pathway in Con A induced autophagy in HeLa cells.
      Subsequently, we found that Con A treatment suppresses the PI3K/Akt/mTOR and up
      regulates the MEK/ERK pathway leading to the activation of autophagy. This study
      will further help us to understand the mechanism behind the autophagic pathway
      induced by Con A and simultaneously it will strengthen its effective use as a
      prospective cancer chemo-therapeutic. 

PMID- 24434246
TI  - Investigation into the cyto-protective and wound healing properties of cryptic
      peptides from bovine Achilles tendon collagen.
AB  - Many proteins have concealed regions in their amino acid sequences that when
      liberated or exposed by conformational changes can exhibit bioactivity. Two such
      cryptic bioactive peptides, C2 (with cell adhesive properties) and E1 (with cell
      adhesive and antioxidant properties) have been isolated from bovine tendon
      collagen. This investigation deals with the efficacy of these peptides in
      countering externally generated stress and imparting cyto-protection in mammalian
      cell systems. The cell survival activity was studied with two cell lines, viz.,
      HeLa and Vero, with varying concentrations of five oxidative stress-generating
      agents. The activities of the peptides in supporting cell adhesion and countering
      stress were determined in their coated and dissolved forms. C2 and E1 coated
      dishes registered 8 times (p<0.01) higher rate of cell survival against oxidative
      stress than collagen coated dishes. E1 increased stress tolerance levels by >100
      times in dissolved form and C2, by 8 times in coated form. The peptides supported
      faster wound closure than collagen under normal as well as stressed condition.
      Maximum stress tolerance was observed on C2 coated dishes in the presence of E1
      in the medium suggesting that both enhanced cell adhesion and antioxidative
      activities significantly contribute to the cell survival during stress. The
      present study emphasizes that collagen peptides, apart from providing a suitable
      surface for cell adhesion, also confer protection to cells against oxidative
      stress. 

PMID- 24434247
TI  - Inhabitants' and professionals' social representations of health determinants in
      a disadvantaged urban area in France: a qualitative analysis.
AB  - BACKGROUND AND OBJECTIVE: Access to care in French disadvantaged urban areas
      remains an issue despite the implementation of local healthcare structures. To
      understand this contradiction, we investigated social representations held by
      inhabitants of such areas, as well as those of social and healthcare
      professionals, regarding events or behaviours that can impact low-income
      individuals' health. METHOD: In the context of a health diagnosis, 288
      inhabitants living in five disadvantaged districts of Aix-les-Bains, as well as
      28 professionals working in these districts, completed an open-ended
      questionnaire. The two groups of respondents were asked to describe what could
      have an impact on health status from the inhabitants' point of view. The textual
      responses were analyzed using the Alceste method. RESULTS: We observed a number
      of differences in the way the inhabitants and professionals represented
      determinants of health in disadvantaged urban areas: the former proposed a
      representation mixing personal responsibility with physiological, social,
      familial, and professional aspects, whereas the latter associated health issues
      with marginalization (financial, drug, or alcohol problems) and personal
      responsibility. Both inhabitants and professionals mentioned control over events
      and lifestyle as determinants of health. DISCUSSION: The results are discussed
      regarding the consequences of these different representations on the beneficiary 
      healthcare-provider relationship in terms of communication and trust.

PMID- 24434248
TI  - Algerian medical teachers' research output and its determinants during the 2000
      2009 decade.
AB  - BACKGROUND: Publications are the primary output of scientific research. We
      conducted a national study to quantify Algerian medical teachers' research output
      and identify its determinants during the 2000-2009 decade. METHODS: The American
      Medline database and the French Pascal database were used. A publication was
      eligible only if the lead author was an Algerian medical teacher (in medicine,
      pharmacy, or dentistry) working in Algeria. The same questionnaire was completed
      by cases (teachers who were first authors of an original article during the study
      period) and randomly selected controls. Logistic regression analysis was used to
      identify factors related to research output. RESULTS: A total of 79 original
      articles (42.2% of publications) were retrieved, a quarter of which were listed
      in Pascal alone. The publication rate was 2.6 original articles per 1000 teachers
      per year. The journals that published these original articles had a median impact
      factor of 0.83. The ability to publish an original article was 4.3 times higher
      if the teacher had undergone training in biostatistics and/or epidemiology
      (adjusted odds ratio [aOR]=4.31, 95% confidence interval [CI]: 1.79-10.38). A
      promotion evaluation grid that did not encourage writing (aOR=3.44, 95% CI: 1.42
      8.33), a doctoral thesis, seniority, foreign collaboration, and English language
      proficiency were found to be associated with publication output. CONCLUSIONS:
      Algerian medical teachers' research output was particularly low. Replacing the
      current promotion grid with a grid that promotes writing, developing abilities to
      read and write articles and developing English language proficiency are likely to
      improve this situation.

PMID- 24434249
TI  - [The analysis of "Big Data" in clinical research].

PMID- 24434250
TI  - Mental health & substance use: challenges for serving older adults.

PMID- 24434251
TI  - Impaired function of upper limb muscles in patients with chronic obstructive
      pulmonary disease.

PMID- 24434252
TI  - Socio-economic dynamics of asthma.

PMID- 24434253
TI  - New treatment strategies for Alzheimer's disease: is there a hope?
AB  - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative
      disease, and corresponds to the most common cause of dementia worldwide. Although
      not fully understood, the pathophysiology of AD is largely represented by the
      neurotoxic events triggered by the beta-amyloid cascade and by cytoskeletal
      abnormalities subsequent to the hyperphosphorylation of microtubule-associated
      Tau protein in neurons. These processes lead respectively to the formation of
      neuritic plaques and neurofibrillary tangles, which are the pathological
      hallmarks of the disease. Clinical benefits of the available pharmacological
      treatment for AD with antidementia drugs (namely cholinesterase inhibitors and
      memantine) are unquestionable, although limited to a temporary, symptomatic
      support to cognitive and related functions. Over the past decade, substantial
      funding and research have been dedicated to the search and development of new
      pharmaceutical compounds with disease-modifying properties. The rationale of such
      approach is that by tackling key pathological processes in AD it may be possible
      to attenuate or even change its natural history. In the present review, we
      summarize the available evidence on the new therapeutic approaches that target
      amyloid and Tau pathology in AD, focusing on pharmaceutical compounds undergoing
      phase 2 and phase 3 randomized controlled trials. 

PMID- 24434255
TI  - Upper limb muscle strength & endurance in chronic obstructive pulmonary disease.
AB  - BACKGROUND & OBJECTIVES: There are very few studies that have investigated the
      muscle strength and endurance of upper limbs (UL) in chronic obstructive
      pulmonary disease (COPD). We undertook this study to measure and compare the
      skeletal muscle strength and endurance of UL in COPD patients and age matched
      healthy controls and to study the association between lung function parameters
      and UL muscle strength and endurance. METHODS: Forty one COPD patients and 45
      height and weight matched healthy subjects of the same age group were studied. UL
      skeletal muscle strength and endurance were measured using the hand grip
      dynamometer test. Forced vital capacity (FVC), forced expiratory volume in 1 sec
      (FEV1), forced expiratory flow during 25-75% FVC (FEF (25-75%)) and peak
      expiratory flow rate (PEFR) were measured. The handgrip muscle strength and
      endurance between the two groups were compared and correlations between FVC and
      FEV 1 with muscle strength and endurance were analyzed. RESULTS: The mean
      handgrip strength and mean muscle endurance in COPD patients were significantly
      lesser than the normal subjects in both males and females (P<0.001). There was
      significant positive correlation between muscle strength and FVC in males (r2
      =0.32, P<0.05); and between muscle strength and FEV1 in females (r2 =0.20,
      P<0.05). INTERPRETATION & CONCLUSION: The study showed that the handgrip muscle
      strength decreases as the FVC and FEV1 decrease in patients with COPD.
      Identifying those patients who have reduced strength and endurance will allow
      early interventions targeted at improving the quality of life of the patient.

PMID- 24434256
TI  - Association of socio-economic status with family history in adult patients with
      asthma.
AB  - BACKGROUND & OBJECTIVES: Socio-economic status is associated with increased
      morbidity in patients with asthma. The aim of the present study was to assess the
      association between socio-economic status and family history of asthma in adult
      asthma patients. METHODS: The study included 200 adults with asthma and 400 non
      asthmatic controls. Socio-economic status was determined based on income.
      Regression analysis was used to estimate odd ratios in relation to socio-economic
      class, using age, gender, family history of asthma and smoking habits. RESULTS:
      The highest occurrence of having any family history of asthma was observed in the
      high class group (88.2%), followed by upper middle class (79.5%), lower middle
      class (60%) and the lowest in the low class group (34%). Having any family
      history of asthma was an important risk factor in both univariate and
      multivariate analyses in lower middle class, upper middle class and high class,
      but not in the low class group. INTERPRETATION AND CONCLUSIONS: The results
      indicated a positive association between having a family history of asthma and
      higher socio-economic status. Further studies on a large representative sample
      need to be conducted to confirm these findings.

PMID- 24434257
TI  - Prevalence of psychiatric morbidity amongst the community dwelling rural older
      adults in northern India.
AB  - BACKGROUND & OBJECTIVES: The population of elderly is growing globally and so are
      the physical illnesses and psychiatric morbidity. This study was planned to
      assess the prevalence and patterns of psychiatric morbidity amongst rural older
      adults in Lucknow, north India. METHODS: A survey was conducted in subjects aged
      60 yr and above to identify the cases of psychiatric morbidity in rural
      population from randomly selected two revenue blocks of Lucknow district, Uttar
      Pradesh, India. All subjects were screened through Hindi Mental Status
      Examination (HMSE) and Survey Psychiatric Assessment Schedule (SPAS) to identify
      for the suspected cases of cognitive and the psychiatric disorders, respectively.
      The subjects screened positive on HMSE and SPAS were assessed in detail on
      Cambridge Mental Disorder of the Elderly Examination-Revised (CAMDEX-R) and
      Schedule for Clinical Assessment in Neuropsychiatry (SCAN), to diagnose cognitive
      disorders and psychiatric disorders (other than the cognitive), respectively on
      the basis of International Classification of Diseases-10 (ICD-10) diagnostic
      guidelines. RESULTS: The overall prevalence of psychiatric morbidity in rural
      older adults was found to be 23.7 per cent (95% CI=21.89-25.53). Mood (affective)
      disorders were the commonest (7.6%, 95% CI=6.51-8.80), followed by mild cognitive
      impairment (4.6%, 95% CI=3.72-5.53), mental and behavioural disorders due to
      substance use (4.0%, 95% CI=3.17-4.87) and dementia (2.8%) [Alzheimer's disease
      (2.4%, 95% CI=1.81-3.16) and vascular (0.4%, 95% CI=0.16-0.73)]. INTERPRETATION &
      CONCLUSIONS: Overall prevalence of psychiatric morbidity amongst rural elderly in
      this study was found to be less in comparison to those reported in earlier
      studies from India. However, prevalence pattern of different disorders was found
      to be similar. Therefore, it appears that a stringent methodology, refined case
      criteria for diagnosis and assessment by trained professionals restrict false
      diagnosis.

PMID- 24434258
TI  - Effect of body mass index on physical self concept, cognition & academic
      performance of first year medical students.
AB  - BACKGROUND & OBJECTIVES: The relationship between obesity and self perception,
      particularly in children and young adults has important implications for physical
      and psychosocial health and well-being. A better understanding of this
      relationship could help target psychology services and public health strategies
      more effectively. The aim of the present study was to assess the effect of body
      mass index (BMI) on physical self concept and cognition of the first year medical
      undergraduate students in a medical college in north India. The relationship
      between physical self concept and academic performance and presence of any gender
      differences were also examined. METHODS: The study was carried out on 18-21 yr
      old first year M.B.B.S. students of Maulana Azad Medical College, New Delhi,
      India. Physical self concept was assessed using short version of Physical Self
      Description Questionnaire (PSDQ-S) which is a psychometrically strong instrument
      for measuring multiple dimensions of physical self-concept. Cognition was
      assessed by P300 evoked potentials and academic performance was evaluated on the
      basis of marks obtained in anatomy, physiology and biochemistry subjects.
      RESULTS: There was no association between BMI and physical self-concept or
      between BMI and cognition. Gender differences on physical self-concept were also
      insignificant. No correlation was seen between physical self-concept and academic
      performance. INTERPRETATION & CONCLUSION: The present results suggest that
      negative consequences of high body mass index on physical self-concept and
      cognition are not seen in young adults. It may be that academic achievement
      nullifies the effect on physical self-concept and the effect on cognition
      accumulates as the age progresses, therefore, appears later in life.

PMID- 24434254
TI  - Benefits & risks of statin therapy for primary prevention of cardiovascular
      disease in Asian Indians - a population with the highest risk of premature
      coronary artery disease & diabetes.
AB  - Several reviews and meta-analyses have demonstrated the incontrovertible benefits
      of statin therapy in patients with cardiovascular disease (CVD). But the role for
      statins in primary prevention remained unclear. The updated 2013 Cochrane review
      has put to rest all lingering doubts about the overwhelming benefits of long-term
      statin therapy in primary prevention by conclusively demonstrating highly
      significant reductions in all-cause mortality, major adverse cardiovascular
      events (MACE) and the need for coronary artery revascularization procedures
      (CARPs). More importantly, these benefits of statin therapy are similar at all
      levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In
      addition to preventing myocardial infarction (MI), stroke, and death, primary
      prevention with statins is also highly effective in delaying and avoiding
      expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no
      evidence of any serious harm or threat to life caused by statin therapy, though
      several adverse effects that affect the quality of life, especially diabetes
      mellitus (DM) have been reported. Asian Indians have the highest risk of
      premature coronary artery disease (CAD) and diabetes. When compared with Whites,
      Asian Indians have double the risk of CAD and triple the risk of DM, when
      adjusted for traditional risk factors for these diseases. Available evidence
      supports the use of statin therapy for primary prevention in Asian Indians at a
      younger age and with lower targets for low-density lipoprotein cholesterol (LDL
      C) and non-high density lipoprotein (non-HDL-C), than those currently recommended
      for Americans and Europeans. Early and aggressive statin therapy offers the
      greatest potential for reducing the continuing epidemic of CAD among Indians. 

PMID- 24434259
TI  - Toll-like receptors, cytokines & nitric oxide synthase in patients with otitis
      media with effusion.
AB  - BACKGROUND & OBJECTIVES: Microbial infections in the normally sterile environment
      of the middle ear cavity in patients with otitis media trigger expression of Toll
      like receptors (TLRs), cytokines, and nitric oxide. We evaluated the expression
      levels of TLR-1, -2, -4, -5, -6, and -9, interleukin (IL)-6, -8, -10, and -12,
      interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and
      nitric oxide (NO), in paediatric patients with otitis media with effusion (OME).
      METHODS: The levels of TLR, cytokine, and nitric oxide synthase (NOS) mRNAs in
      middle ear effusion were assessed by real-time polymerase chain reaction in 96
      children with OME, 24 prone and 72 not prone to otitis. The level of expression
      of each mRNA was compared in the otitis-prone and non-otitis-prone groups, in
      patients with and without bacteria, and by frequency of ventilation tube
      insertion. RESULTS: The expression of TLR-1, -2, -4, -5, -6, and -9; IL-6, -8, 
      10, and -12; IFN-gamma; TNF-alpha; and NOS mRNAs in the effusion fluid of both
      the otitis-prone and non-otitis-prone groups were measured. The expression levels
      of TLR-2, -4, -6, and -9 mRNA were significantly lower in the otitis-prone than
      in the non-otitis-prone group (P<0.05). Although higher levels of TLR, cytokine,
      and NOS mRNAs were generally observed in culture positive than in culture
      negative patients, none of these differences was statistically significant. No
      differences were observed in the expressions relative to the frequencies of
      ventilation tube insertion. INTERPRETATION & CONCLUSIONS: TLRs, cytokines, and
      NOS, which act cooperatively in the innate immune response, were closely
      associated with OME. Decreased expression of TLRs may be associated with
      increased susceptibility to OME.

PMID- 24434260
TI  - Evaluation of the effectiveness of diagnostic & management decision by
      teleophthalmology using indigenous equipment in comparison with in-clinic
      assessment of patients.
AB  - BACKGROUND & OBJECTIVES: There is a concern on the quality and the usefulness of
      teleophthalmology images, particularly those using indigenous equipment, in
      making a diagnosis and treatment decisions in ophthalmology. The present study
      was done to compare the level of agreement and sensitivity and specificity of
      diagnosis and management decisions of various eye diseases by teleophthalmology
      using indigenous equipment, compared to the in-clinic assessment. METHODS:
      Patients having different eye diseases were evaluated by two ophthalmologists -
      one ophthalmologist examined the patient in clinic setting while the other
      ophthalmologist made the diagnosis and management decision based on images sent
      by teleophthalmology. The images were taken by the ophthalmic technician using
      digital imaging system and fundus camera. The clinical findings and management
      decisions by the two ophthalmologists were masked to each others. RESULTS: In
      diagnosis of anterior segment eye diseases such as cataract and corneal diseases
      there was good to very good agreement (kappa values of 0.68 and 0.91 for cataract
      and corneal diseases respectively) between in-clinic assessment and assessment by
      teleophthalmology. There was moderate agreement (kappa values of 0.52 and 0.48
      for glaucoma and retinal diseases respectively) between in-clinic assessment and
      assessment by teleophthalmology for the diagnosis of glaucoma and retinal
      diseases. For the management decisions of patients, there was moderate level of
      agreement in all groups of eye diseases. INTERPRETATION & CONCLUSIONS:
      Teleophthalmology, using indigenous equipment was found to be effective in
      diagnosis and management decision of anterior segment eye diseases such as
      cataract and cornea, and with some modification and continuous training to the
      technicians could become an effective tool for screening and referral of glaucoma
      and retinal diseases.

PMID- 24434261
TI  - Twelve months fixed duration WHO multidrug therapy for multibacillary leprosy:
      incidence of relapses in Agra field based cohort study.
AB  - BACKGROUND & OBJECTIVES: The reported low relapse rates after 24 months multidrug
      therapy (MDT) for multibacillary leprosy (MB) led to the recommendation of
      reducing duration of therapy to 12 months. However, only a few reports exist on
      long term follow up data after 12 months fixed duration therapy (FDT). The
      present study was done to assess the incidence of relapse in MB leprosy patients
      after 12 months treatment. METHODS: The leprosy patients detected in field
      surveys during 2001-2006 in Agra district, Uttar Pradesh, India, were put on WHO
      MDT and followed up for treatment completion, relapse, reactions and development
      of disability. The assessment was done clinically by following up the patients
      until January 2011. Data collected were analyzed for risk and survival analysis.
      RESULTS: The incidence of relapse was found to be 1.97/100 person years of follow
      up. The incidence of relapse by age (34 yr vs >34 yr), sex (male vs female),
      delay in detection (<36 months vs >36 months) and smear status (smear +ve vs -ve)
      was not found to be significantly different but patients with no nerve
      involvement were observed to have significantly higher relapses than those with
      three or more nerve involvement (P<0.05). Similarly, borderline-borderline and BB
      with reaction (BB/BBR) patients were observed to have significantly high relapses
      than among those with borderline tuberculoid or BT with reaction (BT/BTR) or
      borderline lipromatous/lepromatous/neuritic (BL/LL/N) type of leprosy (P<0.01).
      INTERPRETATION & CONCLUSION: From the observations in the study, it can be
      suggested that relapses occur in 12 months FDT and almost as much as reported in
      24 months FDT for MB leprosy. Although, early relapses may be due to insufficient
      treatment, late relapses may be due to persistent dormant mycobacteria. However,
      a study relating to immunological response of treatment and change in
      immunological profile relating to the occurrence of relapses and its clinical
      correlates may suggest better information on causes of relapses.

PMID- 24434262
TI  - Effects of different methods of decontamination for successful cultivation of
      Mycobacterium tuberculosis.
AB  - BACKGROUND & OBJECTIVES: There has been an extensive invasion of tuberculosis at
      the global level by multidrug resistant as well as extensively drug resistant
      organisms. Attempts to recover the pathogen in pure culture have frequently
      failed since the specimens are often highly contaminated and also due to use of
      insufficient or over-active decontamination procedures. Hence in the present
      study different methods of decontamination were tested to evaluate their
      independent efficacies for culture of Mycobacterium tuberculosis. METHODS: A
      total of 359 samples (241 sputum, 59 urine, 50 endometrium biopsy, 9 pus samples)
      from clinically suspected cases of tuberculosis were subjected to four different
      methods of decontamination followed by inoculation in Lowenstein-Jensen medium
      (LJM), and bilayered medium (BLM) and Kirchner's liquid medium (KLM) to determine
      the influence of differential decontamination processes. Sputum scanty and
      positive specimens were graded and each sample was subjected to decontamination
      by four different techniques. RESULTS: Treatment of specimens with 4 per cent
      NaOH yielded minimum recovery of pure cultures, while use of 2 per cent NaOH
      produced higher number of contaminants compared to other methods of
      decontamination. Addition of N-acetyl L-cystein (NALC) coupled with 2 per cent
      NaOH to the samples for decontamination provided fairly reasonable recovery, but
      the highest number of M. tuberculosis cultures could be obtained when the
      specimens were treated with tri-sodium phosphate and benzalkonium (TSPB). Among
      the sputum positive cases recovery of growth of M. tuberculosis was higher with
      greater number of bacilli present in the specimens. Regarding the influence of
      culture media, BLM produced not only rapid growth, but reasonably higher rate of
      isolation of M. tuberculosis. INTERPRETATION & CONCLUSIONS: Although use of TSPB
      was found to be an efficient method of decontamination for successful isolation
      of M. tuberculosis from contaminated samples, both NALC+ 2 per cent NaOH and TSPB
      also showed significant recovery of M. tuberculosis cultures in BLM that can
      facilitate early diagnosis and initiation of treatment.

PMID- 24434263
TI  - Phenotypic & genotypic characterization of vancomycin resistant Enterococcus
      isolates from clinical specimens.
AB  - BACKGROUND & OBJECTIVES: Enterococci have emerged as important nosocomial
      pathogens and emergence of resistance to many of the antimicrobials used for Gram
      positive organisms has made the management of infections due to Enterococcus
      species difficult. Resistance to glycopeptide antibiotics, especially vancomycin
      is of special concern. This study was undertaken to perform a phenotypic and
      genotypic characterization of vancomycin resistant Enterococcus (VRE) isolates
      obtained from clinical samples in a tertiary care hospital in southern India.
      METHODS: Susceptibility testing was performed for Enterococcus isolates collected
      over a period of one year (November 2008-October 2009). Minimum inhibitory
      concentrations (MIC) of vancomycin and teicoplanin were determined for the
      isolates by the agar dilution method. Genotypic characterization of VRE isolates
      was done by performing multiplex polymerase chain reaction (PCR) for detecting
      the various vancomycin resistance genes. RESULTS: Of the 367 isolates of
      Enterococcus species isolated, 32 were found to be resistant to vancomycin after
      MIC testing. VanA was the commonest phenotype of vancomycin resistance and the
      commonest genotype was vanA. Among the other important findings of the study was
      the presence of heterogeneity in isolates of VRE with the vanA gene cluster with
      regards to resistance to teicoplanin and the coexistence of vanA and vanC1 gene
      clusters in an isolate of E. gallinarum which conferred high level glycopeptide
      resistance to the isolate. INTERPRETATION & CONCLUSIONS: Enterococcus species
      have emerged as important nosocomial pathogens in our patients with a capacity to
      cause a variety of infections. The vancomycin resistance among Enterococcus
      isolates was 8.7 per cent in our study which was high compared to other Indian
      studies. VanA was the commonest phenotype of glycopeptide resistance and vanA was
      the commonest vancomycin resistance gene. The study also demonstrates phenotypic
      as well as genotypic heterogeneity among isolates of VRE from clinical specimens.

PMID- 24434264
TI  - Assessment of phylogenetic affiliation using 16S rRNA gene sequence analysis for
      Pseudomonas aeruginosa in patients of lower respiratory tract infection.

PMID- 24434265
TI  - Research & policy disconnect: the case of rabies research in India.

PMID- 24434266
TI  - Higher homocysteine levels in young Indian adults: impact of vitamin B12 & folate
      deficiencies.

PMID- 24434267
TI  - Analyzing trends- a comment on epidemiological trends of RF/RHD in school
      children of Shimla in north India.

PMID- 24434268
TI  - Anomalous origin of left coronary artery in an adult.

PMID- 24434269
TI  - Pancreatic cancer in a case of idiopathic chronic pancreatitis.

PMID- 24434271
TI  - Increased IL-23 receptor, TNF-alpha and IL-6 expression in individuals with the
      IL23R-IL12RB2 locus polymorphism.

PMID- 24434272
TI  - Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in
      hepatitis C cirrhosis.
AB  - Hepatitis C cirrhosis is associated with a profound disappearance of memory B
      cells. We sought to determine if this loss is associated with the expansion of
      the CD27(-)CD21(-) tissue-like memory B-cells with features of B-cell exhaustion.
      To this end, we quantified the frequency of CD27(-)CD21(-) B-cells in healthy,
      non-cirrhotic HCV-infected, and cirrhotic patients. We examined the expression of
      putative inhibitory receptors, the proliferative and immunoglobulin-secreting
      capacity of CD27/CD21-defined B-cell subsets upon B-cell receptor and/or CD40
      stimulation. We found that CD27(-)CD21(-) B-cells are significantly increased in
      frequency relative to healthy donors in HCV-infected patients. CD27(-)CD21(-) B
      cells were hypoproliferative relative to naive and resting memory B-cells upon
      agonistic stimulation, but retained similar capacity for antibody secretion.
      CONCLUSION: CD27(-)CD21(-) tissue-like memory B-cells with exhausted
      proliferation circulate at increased frequency in cirrhotic and non-cirrhotic HCV
      infected patients. This B-cell subset does not appear anergic, exhibiting
      immunoglobulin-secreting capacity on CD40 agonism indistinguishable from other
      CD27/CD21-defined B-cell subsets.

PMID- 24434274
TI  - Monodispersed LaF3 nanocrystals: shape-controllable synthesis, excitation-power
      dependent multi-color tuning and intense near-infrared upconversion emission.
AB  - In this study, monodispersed and high-quality hexagonal phase LaF3 nanocrystals
      with different shapes and sizes were synthesized by a solvothermal method using
      oleic acid as the stabilizing agent. The as-prepared LaF3 nanocrystals were
      characterized by transmission electron microscopy (TEM), x-ray diffraction (XRD),
      and analysis of the upconversion spectra. The TEM results reveal that the samples
      present high uniformity and monodispersity and are self-assembled into a two
      dimensional ordered array. Moreover, the shape, size and structure of the
      nanocrystals can be readily tuned by adjusting the NaF content. With increasing
      content of NaF, the shape of the LaF3 nanocrystals changed from particle to rod
      and the size gradually increased. More importantly, high NaF content favors the
      formation of one-dimensional nanorods. High Y b(3+) and Er(3+) content is
      beneficial to synthesizing the hexagonal phase of NaLaF4 nanocrystals.
      Furthermore, the TEM results show that the shape and size of the LaF3
      nanocrystals can also be tuned by doping lanthanide ions, which provides a new
      route for size and shape control of nanocrystals. In addition, LaF3 nanocrystals
      co-doped with Y b(3+)/Tm(3+) present efficient near-infrared (NIR)-NIR
      upconversion luminescence. More importantly, the upconversion luminescent colors
      can be readily tuned from blue-white to blue by adjusting the excitation power.
      Therefore, it is expected that these LaF3 nanocrystals with well-controlled
      shape, size and NIR-NIR upconversion emission have potential applications in
      biomedical imaging fields. 

PMID- 24434275
TI  - Microsatellite instability testing in colorectal carcinoma: a practical guide.

PMID- 24434273
TI  - A T cell gene expression panel for the diagnosis and monitoring of disease
      activity in patients with systemic lupus erythematosus.
AB  - Systemic Lupus Erythematosus (SLE) remains a challenging disease to diagnose and
      follow, as no reliable biomarkers are known to date. We designed a gene
      expression panel with 40 genes known to play a role in SLE pathogenesis. We found
      that the combined expression of these genes in SLE T cells can accurately
      differentiate SLE from healthy individuals and patients with other autoimmune
      diseases. The accuracy of the test increased further (83%) when only three out of
      the initial genes (OAS2, CD70 and IL10) were used. A T cell score, calculated
      from the combined expression levels of these genes, correlated positively with
      various SLE activity markers in a cross-sectional cohort and in a few patients
      that were followed prospectively. These data showcase the usefulness of measuring
      mRNA levels of key molecules in diagnosing and following patients with SLE. 

PMID- 24434276
TI  - Immediate effects of unaffected arm exercise in poststroke patients with spastic
      upper limb hemiparesis.
AB  - BACKGROUND: Spasticity is a major disabling symptom in stroke patients.
      Clinically, one of the goals of management of stroke patients should be to reduce
      spasticity. Recent evidence suggests that motor recovery after stroke comprises a
      hierarchical, dynamic framework of interacting mechanisms in brain cortex. We
      hypothesized that unaffected arm exercise can stimulate the ipsilateral motor
      cortex and change the affected upper limb function and spasticity in stroke
      patients. To test the hypothesis, we evaluated the effects of unaffected arm
      exercise on spasticity of the affected upper limb and motor function in stroke
      patients. METHODS: The study was performed in 41 chronic stroke patients with
      upper limb hemiparesis. Affected upper limb spasticity and function were assessed
      at baseline and after each intervention by the modified Ashworth Scale and Fugl
      Meyer Assessment, respectively. Patients were also evaluated clinically by the
      modified Rankin Scale, Functional Independence Measurement and National
      Institutes of Health Stroke Scale. Subjects stood for 10 min during the control
      period, and then cycled an arm crank ergometer at 50% of maximum work load for 10
      min by the unaffected arm in standing position. RESULTS: The mean age at study
      entry was 64.6 +/- 1.7 years. The latency between onset of stroke and the study
      was 109.0 +/- 17.0 months (range, 6-495). The cause of hemiparesis was cerebral
      infarction (n = 21), intracerebral hemorrhage (n = 17) or subarachnoid hemorrhage
      (n = 3). Exercise significantly improved the modified Ashworth Scale compared
      with baseline (p < 0.0001). No such change was noted after the control
      intervention. The Fugl-Meyer Assessment score did not change after exercise
      compared with baseline (p = 0.95). CONCLUSIONS: We conclude that 10 min of
      unaffected arm exercise improves the affected upper limb spasticity in stroke
      patients. Further studies are needed to determine the exact mechanism of such
      improvement and the long-term effects of unaffected arm exercise on motor
      performance.

PMID- 24434278
TI  - Evaluation of albumin structural modifications through cobalt-albumin binding
      (CAB) assay.
AB  - Human serum albumin (HSA) is the most abundant protein in the human body. HSA
      injections prepared by fractionating human blood have mainly covered the demand
      for albumin to treat hypoalbuminemia, the state of low concentration of albumin
      in blood. HSA in solution may exist in various forms such as monomers, oligomers,
      polymers, or as mixtures, and its conformational change and/or aggregation may
      occur easily. Considering these characteristics, there is a great chance of
      modification and polymer formation during the preparation processes of albumin
      products, especially injections. The albumin cobalt binding (ACB) test reported
      by Bar-Or et al. was originally designed to detect ischemia modified albumin
      (IMA), which contains the modified HSA N-terminal sequence by cleavage of the
      last two amino acids. In this study, we developed a cobalt albumin binding (CAB)
      assay to correct the flaws of the ACB test with improving the sensitivity and
      precision. The newly developed CAB assay easily detects albumin configuration
      alterations and may be able to be used in developing a quality control method for
      albumin and its pharmaceutical formulations including albumin injections. 

PMID- 24434277
TI  - Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV
      1 miRNA expression.
AB  - Methamphetamine is the second most frequently used illicit drug in the United
      States. Methamphetamine abuse is associated with increased risk of HIV-1
      acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a
      direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be
      established in patients, methamphetamine has been shown to increase HIV-1
      replication in macrophages, dendritic cells, and cells of HIV transgenic mice.
      Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+)
      T cells that serve as the primary targets of infection in vivo are not clearly
      understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in
      the presence of methamphetamine in a dose-dependent manner. Our results
      demonstrate that methamphetamine had a minimal effect on HIV-1 replication at
      concentrations of 1 to 50 MUmol/L. However, at concentrations >100 MUmol/L, it
      inhibited HIV-1 replication in a dose-dependent manner. We also discovered that
      methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR
      150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up
      regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are
      contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by
      increasing HIV-1 replication. Therefore, our findings underline the complex
      interaction between drug use and HIV-1 and necessitate comprehensive
      understanding of the effects of methamphetamine on HIV-1 pathogenesis. 

PMID- 24434279
TI  - Extensive intestinal first-pass metabolism of arctigenin: evidenced by
      simultaneous monitoring of both parent drug and its major metabolites.
AB  - The current study aims to investigate intestinal absorption and metabolism of
      arctigenin (AR) through simultaneous monitoring of AR and its major metabolites
      in rat plasma. An UPLC/MS/MS assay was developed with chromatographic separation
      of all analytes achieved by a C18 Column (3.9mm*150mm, 3.5MUm) and a gradient
      elution with acetonitrile and 0.1% formic acid within 9min. Sample extraction
      with acetonitrile was optimized to achieve satisfactory recovery for both AR and
      its major metabolites. The lower limit of quantification (LLOQ) for all analytes
      was 25ng/ml. The intra-day and inter-day precision and accuracy of each analyte
      at LLOQ and three quality control (QC) concentrations (low, middle and high) in
      rat plasma was within 15.0% RSD and 15.0% bias. The extraction recoveries were
      within the range of 83.8-94.0% for all analytes. The developed and validated
      assay was then applied to the absorption study of AR in both Caco-2 cell
      monolayer model and in situ single-pass rat intestinal perfusion model. High
      absorption permeability of AR was demonstrated in both models with Papp of
      (1.76+/-0.48)*10(-5) (A->B) (Caco-2) and Pblood of (8.6+/-3.0)*10(-6)cm/s
      (intestinal perfusion). Extensive first-pass metabolism of AR to arctigenic acid
      (AA) and arctigenin-4'-O-glucuronide (AG) was identified in rat intestinal
      perfusion study with Cummins's extraction ratios of 0.458+/-0.012 and 0.085+/
      0.013, respectively. The current assay method demonstrated to be a practical tool
      for pharmacokinetics investigation of AR with complicated metabolism pathways and
      multiple metabolites. 

PMID- 24434280
TI  - Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3): the V54L
      mutation restricting the steroid alternative binding and enhancing the 20alpha
      HSD activity.
AB  - Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3) has an essential
      role in the inactivation of 5alpha-dihydrotestosterone (DHT). Notably, human
      3alpha-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid
      dehydrogenase (20alpha-HSD) and there is only one amino acid difference (residue
      54) that is located in their steroid binding pockets. However, 20alpha-HSD
      displays a distinctive ability in transforming progesterone to 20alpha-hydroxy
      progesterone (20alpha-OHProg). In this study, to understand the role of residue
      54 in the steroid binding and discrimination, the V54L mutation in human 3alpha
      HSD3 has been created. We have solved two crystal structures of the 3alpha
      HSD3.NADP(+).Progesterone complex and the 3alpha-HSD3 V54L.NADP(+).progesterone
      complex. Interestingly, progesterone adopts two different binding modes to form
      complexes within the wild type enzyme, with one binding mode similar to the
      orientation of a bile acid (ursodeoxycholate) in the reported ternary complex of
      human 3alpha-HSD3.NADP(+).ursodeoxycholate and the other binding mode resembling
      the orientation of 20alpha-OHProg in the ternary complex of human 20alpha
      HSD.NADP(+).20alpha-OHProg. However, the V54L mutation directly restricts the
      steroid binding modes to a unique one, which resembles the orientation of 20alpha
      OHProg within human 20alpha-HSD. Furthermore, the kinetic study has been carried
      out. The results show that the V54L mutation significantly decreases the 3alpha
      HSD activity for the reduction of DHT, while this mutation enhances the 20alpha
      HSD activity to convert progesterone. 

PMID- 24434281
TI  - Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in
      specific brain regions that primarily related to memory, neuroendocrine and
      integration.
AB  - As one of the third generation of aromatase inhibitors, letrozole is a favored
      drug for the treatment of hormone receptor-positive breast cancer with some
      adverse effects on the nervous system, but the knowledge is limited and the
      results are controversial, the mechanism underlying its central action is also
      unclear. Accumulated evidences have demonstrated that estrogens derived from
      androgens by aromatase play profound roles in the brain through their receptors,
      which needs coactivator for the transcription regulation, among which steroid
      receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in
      the brain, but whether it is regulated by letrozole is currently unknown. In this
      study, we examined letrozole regulation on SRC-1 expression in adult mice brain
      using immunohistochemistry. The results showed that letrozole induced dramatic
      decrease of SRC-1 in the medial septal, hippocampus, medial habenular nucleus,
      arcuate hypothalamic nucleus and superior colliculus (p<0.01). Significant
      decrease was detected in the dorsal lateral septal nucleus, bed nucleus of stria
      terminalis, ventral taenia tecta, dorsomedial and ventromedial hypothalamic
      nuclei, dorsomedial periaqueductal gray, superior paraolivary nucleus and pontine
      nucleus (p<0.05). In the hippocampus, levels of estradiol content, androgen
      receptor, estrogen receptor alpha and beta also decreased significantly after
      letrozole injection. The above results demonstrated letrozole downregulation of
      SRC-1 in specific regions that are primarily related to learning and memory,
      cognition and mood, neuroendocrine as well as information integration, indicating
      that SRC-1 may be one important downstream central target of letrozole.
      Furthermore, these potential central adverse effects of letrozole should be taken
      into serious considerations. 

PMID- 24434282
TI  - In vitro and in vivo evaluation of a 3beta-androsterone derivative as inhibitor
      of 17beta-hydroxysteroid dehydrogenase type 3.
AB  - 17beta-Hydroxysteroid dehydrogenase type 3 (17beta-HSD3 or HSD17B3) catalyzes the
      last step in the biosynthesis of the potent androgen testosterone (T), by
      stereoselectively reducing the C17 ketone of 4-androstene-3,17-dione (4-dione),
      with NADPH as cofactor. Since T plays an important role in androgen-sensitive
      diseases, this enzyme is thus an interesting therapeutic target. In an attempt to
      design compounds to lower the level of T, we synthesized androsterone derivatives
      substituted at position 3 as inhibitors of 17beta-HSD3, and selected one of the
      most potent compounds for additional studies. In an enzymatic assay in
      homogenized and whole HEK-293 cells overexpressing 17beta-HSD3, the inhibitor RM
      532-105 efficiently inhibited the conversion of natural substrate 4-dione (50nM)
      into T with an IC50 of 26nM and 5nM, respectively. Moreover, the inhibitor RM-532
      105 (10mg/kg) reached a plasma concentration of 250ng/mL at 7h (AUC 24h:
      3485ngh/mL) after subcutaneous (s.c.) injection in the rat. In order to mimic the
      human situation in which 4-dione is converted to T in the testis, we used intact
      rats. Treatment for 7 days with 17beta-HSD3 inhibitor RM-532-105 by s.c.
      injection or oral gavage exerted no effect on the testis, prostate and seminal
      vesicle weight and no modification in the levels of plasma steroids. However,
      after this treatment, the concentration of inhibitor in plasma increased
      depending on the dose. We thereafter determined the concentration of inhibitor in
      the testis and we discovered that the compound was slightly present. In fact, at
      10mg/kg, the inhibitor RM-532-105 seems to have difficulty penetrating inside the
      testis and was found to be concentrated in the testicular capsule, and therefore
      unable to inhibit the 17beta-HSD3 located inside the testis. However, with a
      higher dose of 50mg/kg injected s.c. in rats, RM-532-105 significantly decreased
      the level of T and dihydrotestosterone measured in plasma at 2h. 

PMID- 24434283
TI  - Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone
      loss during vitamin D-deficiency.
AB  - There are several lines of evidence that demonstrate the ability of 1,25
      dihydroxyvitamin D (1,25(OH)2D3), acting via the vitamin D receptor (VDR) to
      mediate negative or positive effects in bone. Transgenic over-expression of VDR
      in osteoblasts and osteocytes in a mouse model (OSVDR) has been previously shown
      to inhibit processes of bone resorption and enhance bone formation, under
      conditions of adequate calcium intake. While these findings suggest that vitamin
      D signalling in osteoblasts and osteocytes promotes bone mineral accrual, the
      vitamin D requirement for this action is not well understood. In this study, 4
      week old female OSVDR and wild-type (WT) mice were fed either a vitamin D-replete
      (1000IU/kg diet, D+) or vitamin D-deficient (D-) diet for 4 months to observe
      changes to bone mineral homeostasis. Tibial bone mineral volume was analysed by
      micro-CT and changes to bone cell activities were measured using standard dynamic
      histomorphometric techniques. While vitamin D-deplete WT mice demonstrated a
      reduction in periosteal bone accrual and overall bone mineral volume, OSVDR mice,
      however, displayed increased cortical and cancellous bone volume in mice which
      remained higher during vitamin D-depletion due to a reduced osteoclast number and
      increased bone formation rate. These data suggest that increased VDR-mediated
      activity in osteoblast and osteocytes prevents bone loss due to vitamin D
      deficiency. This article is part of a Special Issue entitled '16th Vitamin D
      Workshop'. 

PMID- 24434284
TI  - DNA damage response (DDR) via NKX3.1 expression in prostate cells.
AB  - It has been reported that NKX3.1 an androgen-regulated homeobox gene restricted
      to prostate and testicular tissues, encodes a homeobox protein, which
      transcriptionally regulates oxidative damage responses and enhances topoisomerase
      I re-ligation by a direct interaction with the ATM protein in prostate cells. In
      this study, we aimed to investigate the role of NKX3.1 in DNA double-strand break
      (DSB) repair. We demonstrate that the DNA damage induced by CPT-11 (irinotecan, a
      topo I inhibitor), doxorubicin (a topo II inhibitor), and H2O2 (a mediator of
      oxidative damage), but not by etoposide (another topo II inhibitor), is
      negatively influenced by NKX3.1 expression. We also examined gammaH2AX((S139))
      foci formation and observed that the overexpression of NKX3.1 resulted a
      remarkable decrease in the formation of gammaH2AX((S139)) foci. Intriguingly, we
      observed in NKX3.1 silencing studies that the depletion of NKX3.1 correlated with
      a significant decrease in the levels of p-ATM((S1981)) and gammaH2AX((S139)). The
      data imply that the DNA damage response (DDR) can be altered, perhaps via a
      decrease in the topoisomerase I re-ligation function; this is consistent with the
      physical association of NKX3.1 with DDR mediators upon treatment of both PC-3 and
      LNCaP cells with CPT-11. Furthermore, the depletion of NKX3.1 resulted in a G1/S
      progression via the facilitation of an increase in E2F stabilization concurrent
      with the suppressed DDR. Thus, the topoisomerase I inhibitor-mediated DNA damage
      enhanced the physical association of NKX3.1 with gammaH2AX((S139)) on the
      chromatin in LNCaP cells, whereas NKX3.1 in the soluble fraction was associated
      with p-ATM((S1981)) and RAD50 in these cells. Overall, the data suggest that
      androgens and NKX3.1 expression regulate the progression of the cell cycle and
      concurrently activate the DDR. Therefore, androgen withdrawal may augment the
      development of an error-prone phenotype and, subsequently, the loss of DNA damage
      control during prostate cancer progression. 

PMID- 24434286
TI  - Investigating the role of site specific synonymous variation in disease
      association studies.
AB  - Synonymous codon changes may not always be neutral indicating their significance
      in disease association studies, which is almost always overlooked. Synonymous
      substitutions may affect protein-folding rates leading to protein misfolding and
      aggregation. Genome wide analysis of 2301 mitochondrial genomes is performed to
      evaluate the significance of synonymous codons in disease association studies.
      The analysis revealed usage of rare codons at several sites in mitochondrial
      genes with rare codon usage higher for hydrophobic amino acids. The analysis
      suggests that variation data in association studies should be analyzed using site
      specific codon usage values to infer the potential phenotypic impact of
      synonymous changes. 

PMID- 24434287
TI  - Norway: health system review.
AB  - Norways five million inhabitants are spread over nearly four hundred thousand
      square kilometres, making it one of the most sparsely populated countries in
      Europe. It has enjoyed several decades of high growth, following the start of oil
      production in early 1970s, and is now one of the richest countries per head in
      the world. Overall, Norways population enjoys good health status; life expectancy
      of 81.53 years is above the EU average of 80.14, and the gap between overall life
      expectancy and healthy life years is around half the of EU average. The health
      care system is semi decentralized. The responsibility for specialist care lies
      with the state (administered by four Regional Health Authorities) and the
      municipalities are responsible for primary care. Although health care expenditure
      is only 9.4% of Norways GDP (placing it on the 16th place in the WHO European
      region), given Norways very high value of GDP per capita, its health expenditure
      per head is higher than in most countries. Public sources account for over 85% of
      total health expenditure; the majority of private health financing comes from
      households out-of-pocket payments.The number of practitioners in most health
      personnel groups, including physicians and nurses, has been increasing in the
      last few decades and the number of health care personnel per 100 000 inhabitants
      is high compared to other EU countries. However, long waiting times for elective
      care continue to be a problem and are cause of dissatisfaction among the
      patients. The focus of health care reforms has seen shifts over the past four
      decades. During the 1970s the focus was on equality and increasing geographical
      access to health care services; during the 1980s reforms aimed at achieving cost
      containment and decentralizing health care services; during the 1990s the focus
      was on efficiency. Since the beginning of the millennium the emphasis has been
      given to structural changes in the delivery and organization of health care and
      to policies intended to empower patients and users. The past few years have seen
      efforts to improve coordination between health care providers, as well as an
      increased attention towards quality of care and patient safety issues. Overall,
      comparing mortality rates amenable to medical intervention suggests that Norway
      is among the better performing European countries. Despite having one of the
      highest densities of physicians in Europe, though, Norway still struggles to
      ensure geographical and social equity in access to health care. 

PMID- 24434288
TI  - A molecular approach to breast imaging.
AB  - Molecular imaging is a multimodality discipline for noninvasively visualizing
      biologic processes at the subcellular level. Clinical applications of
      radionuclide-based molecular imaging for breast cancer continue to evolve. Whole
      body imaging, with scintimammography and PET, and newer dedicated breast imaging
      systems are reviewed. The potential clinical indications and the challenges of
      implementing these emerging technologies are presented. 

PMID- 24434289
TI  - In vivo tracking of Th1 cells by PET reveals quantitative and temporal
      distribution and specific homing in lymphatic tissue.
AB  - Although T cells can be labeled for noninvasive in vivo imaging, little is known
      about the impact of such labeling on T-cell function, and most imaging methods do
      not provide holistic information about trafficking kinetics, homing sites, or
      quantification. METHODS: We developed protocols that minimize the inhibitory
      effects of (64)Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) ((64)Cu-PTSM)
      labeling on T-cell function and permit the homing patterns of T cells to be
      followed by PET. Thus, we labeled ovalbumin (OVA) T-cell receptor transgenic
      interferon (IFN)-gamma-producing CD4(+) T (Th1) cells with 0.7-2.2 MBq of (64)Cu
      PTSM and analyzed cell viability, IFN-gamma production, proliferation, apoptosis,
      and DNA double-strand breaks and identified intracellular (64)Cu accumulation
      sites by energy dispersive x-ray analysis. To elucidate the fate of Th1 cell
      homing by PET, 10(7 64)Cu-OVA-Th1 cells were injected intraperitoneally or
      intravenously into healthy mice. To test the functional capacities of (64)Cu-OVA
      Th1 cells during experimental OVA-induced airway hyperreactivity, we injected
      10(7 64)Cu-OVA-Th1 cells intraperitoneally into OVA-immunized or nonimmunized
      healthy mice, which were challenged with OVA peptide or phosphate-buffered saline
      or remained untreated. In vivo PET investigations were followed by
      biodistribution, autoradiography, and fluorescence-activated cell sorting
      analysis. RESULTS: PET revealed unexpected homing patterns depending on the mode
      of T-cell administration. Within 20 min after intraperitoneal administration,
      (64)Cu-OVA-Th1 cells homed to the perithymic lymph nodes (LNs) of naive mice.
      Interestingly, intravenously administered (64)Cu-OVA-Th1 cells homed
      predominantly into the lung and spleen but not into the perithymic LNs. The
      accumulation of (64)Cu-OVA-Th1 cells in the pulmonary LNs (6.8 +/- 1.1 percentage
      injected dose per cubic centimeter [%ID/cm(3)]) 24 h after injection was highest
      in the OVA-immunized and OVA-challenged OVA airway hyperreactivity-diseased
      littermates 24 h after intraperitoneal administration and lowest in the untreated
      littermates (3.7 +/- 0.4 %ID/cm(3)). As expected, (64)Cu-OVA-Th1 cells also
      accumulated significantly in the pulmonary LNs of nonimmunized OVA-challenged
      animals (6.1 +/- 0.5 %ID/cm(3)) when compared with phosphate-buffered saline
      challenged animals (4.6 +/- 0.5 %ID/cm(3)). CONCLUSION: Our protocol permits the
      detection of Th1 cells in single LNs and enables temporal in vivo monitoring of T
      cell homing over 48 h. This work enables future applications for (64)Cu-PTSM
      labeled T cells in clinical trials and novel therapy concepts focusing on T-cell
      based immunotherapies of autoimmune diseases or cancer.

PMID- 24434290
TI  - Glial activation in the early stages of brain metastasis: TSPO as a diagnostic
      biomarker.
AB  - Metastatic spread of cancer cells to the brain is associated with high mortality,
      primarily because current diagnostic tools identify only well-advanced
      metastases. Brain metastases have been shown to induce a robust glial response,
      including both astrocyte and microglial activation. On the basis of these
      findings, we hypothesized that this stromal response may provide a sensitive
      biomarker of tumor burden, in particular through the use of SPECT/PET imaging
      agents targeting the translocator protein (TSPO) that is upregulated on activated
      glia. Our goals, therefore, were first to determine the spatial and temporal
      profile of glial activation during early metastasis growth in vivo and second to
      assess the potential of the radiolabeled TSPO ligand (123)I-DPA-713 for early
      detection of brain metastases. METHODS: Metastatic mouse mammary carcinoma 4T1
      green fluorescent protein cells were injected either intracerebrally or
      intracardially into female BALB/c mice to induce brain metastases. Astrocyte and
      microglial activation was assessed immunohistochemically over a 28-d period,
      together with immunofluorescence detection of TSPO upregulation. Subsequently,
      SPECT imaging and autoradiography were used to determine in vivo binding of
      (123)I-DPA-713 at metastatic sites. RESULTS: Dynamic astrocyte and microglial
      activation was evident throughout the early stages of tumor growth, with the
      extent of astrocyte activation correlating significantly with tumor size (P <
      0.0001). Microglial activation appeared to increase more rapidly than astrocyte
      activation at the earlier time points, but by later time points the extent of
      activation was comparable between the glial cell types. Upregulation of TSPO
      expression was found on both glial populations. Both autoradiographic and in vivo
      SPECT data showed strong positive binding of (123)I-DPA-713 in the
      intracerebrally induced model of brain metastasis, which was significantly
      greater than that observed in controls (P < 0.05). (123)I-DPA-713 binding was
      also evident autoradiographically in the intracardially induced model of brain
      metastasis but with lower sensitivity because of smaller tumor size (~ 100-MUm
      diameter vs. ~ 600-MUm diameter in the intracerebral model). CONCLUSION: These
      data suggest that the glial response to brain metastasis may provide a sensitive
      biomarker of tumor burden, with a tumor detection threshold lying between 100 and
      600 MUm in diameter. This approach could enable substantially earlier detection
      of brain metastases than the current clinical approach of gadolinium-enhanced MR
      imaging.

PMID- 24434291
TI  - Improvement of attenuation correction in time-of-flight PET/MR imaging with a
      positron-emitting source.
AB  - Quantitative PET imaging relies on accurate attenuation correction. Recently,
      there has been growing interest in combining state-of-the-art PET systems with MR
      imaging in a sequential or fully integrated setup. As CT becomes unavailable for
      these systems, an alternative approach to the CT-based reconstruction of
      attenuation coefficients (MU values) at 511 keV must be found. Deriving MU values
      directly from MR images is difficult because MR signals are related to the proton
      density and relaxation properties of tissue. Therefore, most research groups
      focus on segmentation or atlas registration techniques. Although studies have
      shown that these methods provide viable solutions in particular applications,
      some major drawbacks limit their use in whole-body PET/MR. Previously, we used an
      annulus-shaped PET transmission source inside the field of view of a PET scanner
      to measure attenuation coefficients at 511 keV. In this work, we describe the use
      of this method in studies of patients with the sequential time-of-flight (TOF)
      PET/MR scanner installed at the Icahn School of Medicine at Mount Sinai, New
      York, NY. METHODS: Five human PET/MR and CT datasets were acquired. The
      transmission-based attenuation correction method was compared with conventional
      CT-based attenuation correction and the 3-segment, MR-based attenuation
      correction available on the TOF PET/MR imaging scanner. RESULTS: The transmission
      based method overcame most problems related to the MR-based technique, such as
      truncation artifacts of the arms, segmentation artifacts in the lungs, and
      imaging of cortical bone. Additionally, the TOF capabilities of the PET detectors
      allowed the simultaneous acquisition of transmission and emission data. Compared
      with the MR-based approach, the transmission-based method provided average
      improvements in PET quantification of 6.4%, 2.4%, and 18.7% in volumes of
      interest inside the lung, soft tissue, and bone tissue, respectively. CONCLUSION:
      In conclusion, a transmission-based technique with an annulus-shaped transmission
      source will be more accurate than a conventional MR-based technique for measuring
      attenuation coefficients at 511 keV in future whole-body PET/MR studies.

PMID- 24434292
TI  - Use of 11C-MPDX and PET to study adenosine A1 receptor occupancy by
      nonradioactive agonists and antagonists.
AB  - Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with
      the radioligand 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C
      MPDX) and PET. Here we investigated whether A1R occupancy by nonradioactive
      agonists and antagonists can be assessed with this technique. METHODS: Small
      animal PET scans with arterial blood sampling were obtained for 4 groups of
      isoflurane-anesthetized Wistar rats: controls (n = 7); pretreated with a
      centrally active A1R agonist, N(6)-cyclopentyladenosine (CPA; 0.25 mg/kg
      intraperitoneally; dissociation constant, 0.48 nM; n = 7); pretreated with a
      moderate dose of caffeine (antagonist for A1Rs and adenosine A2A receptors; 4
      mg/kg intraperitoneally; dissociation constant, 11 MUM; n = 6); and pretreated
      with a high dose of caffeine (40 mg/kg intraperitoneally; n = 6). RESULTS: The
      administration of CPA resulted in a strong reduction (>50%) in the heart rate,
      and caffeine administration resulted in a small increase (10%-15%). A caffeine
      dose of 4 mg/kg (n = 6) resulted in 65.9% A1R occupancy, and a dose of 40 mg/kg
      (n = 6) resulted in 98.5% occupancy (calculated from a modified Lassen plot).
      However, the administration of CPA resulted in an increase in (11)C-MPDX binding
      in the brain. CONCLUSION: Small-animal PET with (11)C-MPDX can be used to assess
      antagonist but not agonist binding at A1Rs. Changes in tracer uptake after the
      administration of CPA resembled previously reported changes induced by treatment
      of rats with ethanol and an adenosine kinase inhibitor (ABT702). Thus, the
      administration of an exogenous agonist or increasing the level of an endogenous
      agonist have similar effects. Agonists and antagonists may bind to different
      sites on the A1R protein having allosteric interactions.

PMID- 24434293
TI  - Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic
      acid-ubiquicidin as a radioligand for PET infection imaging.
AB  - Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate
      between mammalian and bacterial or fungal cells. (99m)Tc-UBI29-41 was previously
      tested for detecting infection in humans using SPECT. For the present study, the
      UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane
      triacetic acid (NOTA), radiolabeled with (68)Ga, and investigated in a rabbit
      infection model. METHODS: (68)Ga was obtained from a 1.85-GBq (68)Ge/(68)Ga
      generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine
      before tracer administration and placed in a clinical PET/CT scanner. (68)Ga
      1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ((68)Ga-NOTA-UBI29
      41) was formulated in saline solution, and 101 +/- 41 MBq were administered
      intravenously. The tracer distribution was studied by PET/CT imaging in animals
      (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and
      turpentine oil-induced muscular inflammations, and (c) bearing ovalbumin-induced
      lung inflammations. Static PET/CT imaging was performed at different time
      intervals up to 120 min after injection. For calculation of target-to-nontarget
      ratios, standardized uptake values were normalized against healthy thigh muscle,
      representing nontargeted tissue. RESULTS: PET/CT images of healthy animals showed
      predominant distribution in the kidneys, liver, and bladder; heart and spleen
      showed moderate, declining uptake, only. The biologic half-life in blood was 29
      min. Urinary accumulation of (68)Ga-NOTA-UBI29-41 peaked at 3.8 +/- 0.91
      percentage injected dose per gram (%ID) at 120 min, and 88 +/- 5.2 %ID was
      recovered in total urine. (68)Ga-NOTA-UBI29-41 imaging in (b) selectively
      visualized the muscular infection site and was differentiated from sterile
      inflammatory processes. Standardized uptake value ratios for muscles
      (infected/inflamed) were 2.9 +/- 0.93, 2.9 +/- 0.50, 3.5 +/- 0.86, and 3.8 +/-
      0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with
      asthma showed insignificant uptake. CONCLUSION: (68)Ga-NOTA-UBI29-41 was strongly
      localized in bacteria-infected areas and minimally detected in a sterile
      inflammation area in rabbit muscles. The findings propose this compound to be an
      excellent first-line PET/CT tracer to allow the distinguishing of infection from
      inflammation.

PMID- 24434294
TI  - Detection of recurrent prostate cancer after radical prostatectomy: comparison of
      11C-choline PET/CT with pelvic multiparametric MR imaging with endorectal coil.
AB  - The aim of this study was to compare (11)C-choline PET/CT with pelvic
      multiparametric MR imaging for detection of recurrent prostate carcinoma in
      patients with suspected recurrence after radical prostatectomy and to identify an
      optimal imaging method to restage these patients. METHODS: This was a
      retrospective, single-institution study of 115 prostatectomy patients with
      suspected tumor recurrence who underwent both (11)C-choline PET/CT and
      multiparametric MR imaging with endorectal coil. The reference standard included
      histopathology, treatment change, and imaging follow-up for determination of
      locally recurrent tumor, lymph node (LN) metastases, and skeletal metastases. Two
      nuclear medicine and 2 genitourinary radiologists independently and in a masked
      manner reviewed PET/CT and multiparametric MR imaging, respectively. The
      reviewers assessed for local recurrence in the prostatectomy bed as well as LN
      and bone metastases, rating their diagnostic confidence with a 5-point scoring
      system for each location. Receiver-operating-characteristic analysis was used to
      compare the 2 modalities. RESULTS: The standard of reference (either positive or
      negative) for the diagnosis of local recurrence and pelvic LN and bone metastases
      was met in 87, 70, and 95 patients, respectively. Documented local recurrence and
      pelvic LN and bone metastases was present in 61 of 87 (70.1%), 50 of 70 (71.4%),
      and 16 of 95 (16.8%) patients, respectively. Patient-based area under the
      receiver-operating-characteristic curves of multiparametric MR imaging versus
      PET/CT for the diagnosis of local recurrence and pelvic LN and bone metastases
      were 0.909 versus 0.761 (P = 0.0079), 0.812 versus 0.952 (P = 0.0064), and 0.927
      versus 0.898 (P = 0.69), respectively. Among 61 patients with local recurrence,
      32 patients (52.4%) were correctly diagnosed as having local recurrence by both
      multiparametric MR imaging and PET/CT, 22 (36.1%) were correctly diagnosed by
      multiparametric MR imaging only, 6 (9.8%) could not be diagnosed by either
      modality, and 1 (1.6%) was correctly diagnosed by PET/CT only. The patient-based
      sensitivity, specificity, and accuracy of multiparametric MR imaging for
      diagnosing local recurrence were 88.5% (54/61), 84.6% (22/26), and 87.4% (76/87)
      whereas those of PET/CT for detecting body LN or bone metastases were 92.3%
      (72/78), 100% (18/18), and 93.8% (90/96), respectively. CONCLUSION:
      Multiparametric MR imaging with endorectal coil is superior for the detection of
      local recurrence, PET/CT is superior for pelvic LN metastasis, and both were
      equally excellent for pelvic bone metastasis. (11)C-choline PET/CT and pelvic
      multiparametric MR imaging are complementary for restaging prostatectomy patients
      with suspected recurrent disease.

PMID- 24434295
TI  - Evaluation of frame-based and event-by-event motion-correction methods for awake
      monkey brain PET imaging.
AB  - PET imaging of nonhuman primates (NHPs) requires correction of head motion if the
      subjects are scanned awake and their heads are unrestrained, because the NHPs
      move their heads faster and more frequently than human subjects. This work
      focuses on designing and validating 2 motion-correction algorithms for awake NHP
      brain PET imaging. METHODS: Two motion-correction methods were implemented for
      awake NHP brain PET imaging: multiacquisition frame (MAF) and event-by-event
      (EBE). Motion data were acquired from an external motion-tracking device. The MAF
      method divides scan data into short subframes, reconstructs each subframe
      individually, and registers them to a reference orientation. This method suffers
      from residual intraframe motion and data loss when motion is large because a
      minimum frame duration is often required. The EBE method, previously implemented
      for a human brain scanner and adapted for a small-animal PET scanner in this
      work, eliminates intraframe motion and should have a best accuracy. We first
      evaluated the accuracy of both motion-correction methods with moving phantom
      scans. Both motion-correction methods were then applied to awake NHP brain PET
      studies with a gamma-aminobutyric acid A-benzodiazepine receptor ligand, (11)C
      flumazenil, and the reconstructed images were compared with those from a motion
      free anesthetized study. RESULTS: The phantom studies showed that EBE motion
      correction recovers the contrast (within 3%) similarly to the static study,
      whereas MAF motion correction using the standard algorithm setting showed a 25%
      reduction in contrast from the static case. In awake NHP brain PET imaging, EBE
      motion correction better recovers the fine structures than the MAF method, as
      compared with anesthetized studies. CONCLUSION: The large magnitude and frequency
      of NHP head motion suggests that EBE motion correction with accurate externally
      measured motion data can noticeably alleviate image blurring due to the
      intraframe motion in the MAF motion-correction method.

PMID- 24434296
TI  - Predictors of long-term outcome in patients with well-differentiated
      gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide
      therapy with 177Lu-octreotate.
AB  - Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors
      (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited,
      especially with regard to the impact of the Ki-67 index. Using a single-center
      analysis, we aimed to establish predictors of survival. METHODS: We
      retrospectively analyzed a consecutive cohort of 74 patients who had metastatic
      GEP NET and underwent PRRT with (177)Lu-octreotate (mean activity of 7.9 GBq per
      cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33
      with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable
      metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or
      clinical progression within less than 12 mo or uncontrolled disease under
      somatostatin analog treatment. Responses were evaluated according to modified
      Southwest Oncology Group criteria. Potential predictors of survival were analyzed
      with the Kaplan-Meier curve method (log-rank test) and multivariate analysis (P <
      0.05). RESULTS: The response rates were 36.5% partial response, 17.6% minor
      response, 35.1% stable disease, and 10.8% progressive disease for the entire
      cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and
      9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1%
      minor response, 48.8% stable disease, and 12.2% progressive disease for
      nonpancreatic GEP NET. The median progression-free survival and overall survival
      were 26 mo (95% confidence interval, 18.3-33.7) and 55 mo (95% confidence
      interval, 48.8-61.2), respectively. Besides the Ki-67 index, a Karnofsky
      performance score of less than or equal to 70%, a hepatic tumor burden of greater
      than or equal to 25%, and a baseline plasma level of neuron-specific enolase of
      greater than 15 ng/mL independently predicted shorter overall survival (hazard
      ratio, 2.1-3.1). Patients with a Ki-67 index of greater than 10% still had median
      progression-free survival and overall survival of 19 and 34 mo, respectively.
      CONCLUSION: The results of this study demonstrated the favorable response and
      long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent
      predictors of survival were the Ki-67 index, the patient's performance status
      (Karnofsky performance scale score), the tumor burden, and the baseline neuron
      specific enolase level. Even patients with a Ki-67 index of greater than 10%
      seemed to benefit from PRRT, with a good response and a notable long-term
      outcome. We present the first evidence, to our knowledge, that even in patients
      with metastatic disease the distinction between G1 and G2-in particular, between
      G1 (Ki-67 index of 1%-2%) and low-range G2 (Ki-67 index of 3%-10%)-provides
      prognostic stratification.

PMID- 24434298
TI  - Low birth weight, preterm births, and intrauterine growth retardation in relation
      to parental smoking during pregnancy.

PMID- 24434297
TI  - Update on key emerging challenges in cystic fibrosis.
AB  - Cystic fibrosis (CF) is a multisystem disease causing severe chronic
      sinopulmonary disease and loss of pancreatic exocrine function, which affects
      approximately 70,000 individuals worldwide. New therapeutic developments over the
      last few decades have resulted in a significant increase in survival, with the
      median predicted survival now reaching the late thirties and more and more CF
      patients living well into adulthood. However, with this advent of new therapies
      and the associated increase in survival, new challenges in CF care have also
      emerged. Two of these challenges, i.e. chronic methicillin-resistant
      Staphylococcus aureus lung infection and patient adherence to very complicated
      and time-consuming therapeutic regimens, are reviewed in detail here. In
      addition, the ultimate challenge of treating the underlying cause of CF by
      correcting the dysfunction of the CF transmembrane conductance regulator chloride
      channel is reviewed, as agents to correct channel function will likely
      significantly alter CF clinical outcomes and treatment approaches in the next
      decade.

PMID- 24434299
TI  - Application of floating silicon-based linear  multielectrode arrays for acute
      recording of single  neuron activity in awake behaving monkeys.
AB  - One of the fundamental challenges in behavioral neurophysiology in awake animals
      is the steady recording of action potentials of many single neurons for as long
      as possible. Here, we present single neuron data obtained during acute recordings
      mainly from premotor cortices of three macaque monkeys using a silicon-based
      linear multielectrode array. The most important aspect of these probes, compared
      with similar models commercially available, is that, once inserted into the brain
      using a dedicated insertion device providing an intermediate probe fixation by
      means of vacuum, they can be released and left floating in the brain. On the
      basis of our data, these features appear to provide (i) optimal physiological
      conditions for extracellular recordings, (ii) good or even excellent signal-to
      noise ratio depending on the recorded brain area and cortical layer, and (iii)
      extreme stability of the signal over relatively long periods. The quality of the
      recorded signal did not change significantly after several penetrations into the
      same restricted cortical sector, suggesting limited tissue damage due to probe
      insertion. These results indicate that these probes offer several advantages for
      acute neurophysiological experiments in awake monkeys, and suggest the
      possibility to employ them for semichronic or even chronic studies.

PMID- 24434300
TI  - Long-term follow-up and mutation analysis of 27 chinese cases of congenital
      hyperinsulinism.
AB  - OBJECTIVES: Long-term clinical follow-up and mutation analysis were performed in
      27 Chinese congenital hyperinsulinism patients. METHOD: 27 hypoglycemia patients
      were diagnosed with CHI within 2 years of age. The long-term clinical outcome was
      analyzed and mutation analysis of 5 hyperinsulinism candidate genes was
      performed. RESULTS: The median onset age of hypoglycemia in the patients was 60
      days; 11 patients showed hypoglycemic symptoms in the neonatal stage, and
      hypoglycemia in most of the patients was first expressed as a seizure. Blood was
      collected during the hypoglycemic episode and insulin levels were significantly
      elevated. ABCC8, KCNJ11, GCK, HNF4a and GLUD1 genes were screened for mutation
      analysis. 14 mutations in ABCC8 or KCNJ11 genes in 12 cases were identified
      (44%). 57% (8/14) of the mutations have not been reported before. 83% (10/12) of
      the patients have a monoallelic mutation. 58% of these 12 patients were predicted
      to be focal. 73% of the patients without KATP channel mutations were sensitive to
      diazoxide. 26 patients were followed over a period of 1-13 years. 50% of all 27
      patients showed brain impairment. CONCLUSIONS: Chinese CHI patients are similar
      to other ethnic groups in terms of prevalence of KATP-HI, onset age, severity of
      hypoglycemia and treatment. Mutations in ABCC8 and KCNJ11 are common causes of
      CHI in Chinese patients. Mutation analysis showed more novel and monoallele
      mutations in KATP genes.

PMID- 24434301
TI  - Statins in low doses reduce VEGF and bFGF serum levels in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND/AIMS: Recent experimental research revealed that statins at low doses
      induce angiogenesis, which in turn may be related to the course of
      atherosclerosis. There are no clinical studies evaluating the effect of 'low
      dose' statins on serum levels of angiogenesis regulators in diabetic subjects. We
      aimed to explain how low doses of statins modify the serum concentrations of two
      potent proangiogenic factors, vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF), in patients with type 2 diabetes. METHODS:
      Measurements of fasting glucose level, HbA1c, 1,5-anhydro-D-glucitol and lipid
      profile were taken from 47 patients with type 2 diabetes treated with low doses
      of atorvastatin (10 mg daily) or simvastatin (10-20 mg daily), from 45 statin
      free patients with type 2 diabetes and from 23 nondiabetic subjects. Measurements
      of VEGF and bFGF in serum were taken using the BDTM Cytometric Bead Array.
      RESULTS AND CONCLUSION: Statins used in low doses in patients with type 2
      diabetes reduce the serum concentration of VEGF and bFGF which suggests
      antiangiogenic potential of these doses. Nevertheless, this effect could be
      neutralized by postprandial hyperglycemia.

PMID- 24434302
TI  - Patient blood management in elective total hip- and knee-replacement surgery
      (part 2): a randomized controlled trial on blood salvage as transfusion
      alternative using a restrictive transfusion policy in patients with a
      preoperative hemoglobin above 13 g/dl.
AB  - BACKGROUND: Patient blood management is introduced as a new concept that involves
      the combined use of transfusion alternatives. In elective adult total hip- or
      knee-replacement surgery patients, the authors conducted a large randomized study
      on the integrated use of erythropoietin, cell saver, and/or postoperative drain
      reinfusion devices (DRAIN) to evaluate allogeneic erythrocyte use, while applying
      a restrictive transfusion threshold. Patients with a preoperative hemoglobin
      level greater than 13 g/dl were ineligible for erythropoietin and evaluated for
      the effect of autologous blood reinfusion. METHODS: Patients were randomized
      between autologous reinfusion by cell saver or DRAIN or no blood salvage device.
      Primary outcomes were mean intra- and postoperative erythrocyte use and
      proportion of transfused patients (transfusion rate). Secondary outcome was cost
      effectiveness. RESULTS: In 1,759 evaluated total hip- and knee-replacement
      surgery patients, the mean erythrocyte use was 0.19 (SD, 0.9) erythrocyte
      units/patient in the autologous group (n = 1,061) and 0.22 (0.9) erythrocyte
      units/patient in the control group (n = 698) (P = 0.64). The transfusion rate was
      7.7% in the autologous group compared with 8.3% in the control group (P = 0.19).
      No difference in erythrocyte use was found between cell saver and DRAIN groups.
      Costs were increased by ?298 per patient (95% CI, 76 to 520). CONCLUSION: In
      patients with preoperative hemoglobin levels greater than 13 g/dl, autologous
      intra- and postoperative blood salvage devices were not effective as transfusion
      alternatives: use of these devices did not reduce erythrocyte use and increased
      costs.

PMID- 24434303
TI  - Effect of simulation training on compliance with difficult airway management
      algorithms, technical ability, and skills retention for emergency cricothyrotomy.
AB  - BACKGROUND: The effectiveness of simulation is rarely evaluated. The aim of this
      study was to assess the impact of a short training course on the ability of
      anesthesiology residents to comply with current difficult airway management
      guidelines. METHODS: Twenty-seven third-year anesthesiology residents were
      assessed on a simulator in a "can't intubate, can't ventilate" scenario before
      the training (the pretest) and then randomly 3, 6, or 12 months after training
      (the posttest). The scenario was built so that the resident was prompted to
      perform a cricothyrotomy. Compliance with airway management guidelines and the
      cricothyrotomy's duration and technical quality were assessed as a checklist
      score [0 to 10] and a global rating scale [7 to 35]. RESULTS: After training, all
      27 residents (100%) complied with the airway management guidelines, compared with
      17 (63%) in the pretest (P < 0.005). In the pretest and the 3-, 6-, and 12-month
      posttests, the median [range] duration of cricothyrotomy was respectively 117 s
      [70 to 184], 69 s [43 to 97], 52 s [43 to 76], and 62 s [43 to 74] (P < 0.0001
      vs. in the pretest), the median [range] checklist score was 3 [0 to 7], 10 [8 to
      10], 9 [6 to 10], and 9 [4 to 10] (P < 0.0001 vs. in the pretest) and the median
      [range] global rating scale was 12 [7 to 22], 30 [20 to 35], 33 [23 to 35], and
      31 [18 to 33] (P < 0.0001 vs. in the pretest). There were no significant
      differences between performance levels achieved in the 3-, 6-, and 12-month
      posttests. CONCLUSION: The training session significantly improved the residents'
      compliance with guidelines and their performance of cricothyrotomy.

PMID- 24434304
TI  - The evaluation and comparison of consecutive high speed centrifugation and
      LipoClear(r) reagent for lipemia removal.
AB  - BACKGROUND: The aim of this study was to evaluate and compare the efficiency of
      high speed centrifugation and LipoClear(r) reagent for lipemia removal in plasma
      samples spiked with Intralipid(r), for 26 biochemistry analytes. MATERIALS AND
      METHODS: A plasma pool was collected. Aliquots of the pool were spiked with
      Intralipid(r) (final concentrations of 300mg/dL and 500mg/dL Intralipid(r)). The
      lipemia was removed from the aliquots by high speed centrifugation or
      LipoClear(r) reagent. 26 analytes were determined in native, lipemic plasma and
      in samples after lipemia removal. The bias from the concentration in the native
      sample was calculated for each parameter for Intralipid(r) concentrations, 300
      and 500mg/dL of Intralipid(r), respectively. Also, the recovery for each
      parameter after processing the samples using high speed centrifugation and
      LipoClear(r) was calculated. The biases and test recoveries were compared with
      the desirable specification for imprecision (DSI) according to Ricos available at
      the Wesgard's website. The bias and recovery for procalcitonin were compared with
      DSI according to Barassi and colleagues. RESULTS: The bias of the spiked samples
      exceeded the DSI at 300mg/L Intralipid(r) for creatinine, glucose, total protein,
      iron and albumin; and for all previously mentioned parameters including CK-MB,
      sodium, potassium, chlorides, magnesium and ALP at concentration of 500mg/L
      Intralipid(r). For the test recovery the DSI criteria were not met for calcium,
      total protein, sodium and chlorides after high speed centrifugation and for
      glucose, calcium, phosphates, magnesium, sodium, potassium, chlorides, ALP, GGT,
      CK-MB, total protein, albumin and troponin T after using LipoClear(r).
      CONCLUSIONS: LipoClear(r) is not suitable for lipemia removal from samples
      designated for glucose, sodium, potassium, chlorides, phosphates, magnesium, CK
      MB, ALP, GGT, total protein, albumin, CRP and troponin T measurements. High speed
      centrifugation should be used for lipemia removal instead for glucose, potassium,
      phosphates, magnesium, CK-MB, ALP, GGT, albumin, CRP and TnT measurements.

PMID- 24434305
TI  - Wheel-running mitigates psychomotor sensitization initiation but not post
      sensitization conditioned activity and conditioned place preference induced by
      cocaine in mice.
AB  - Previous literature suggests that physical exercise allowed by an unlimited
      access to a running wheel for several weeks can mitigate chronic neurobehavioral
      responsiveness to several addictive drugs in rodents. Here, the potential
      preventive effects of unlimited wheel-running on the initiation of psychomotor
      sensitization and the acquisition and extinction of conditioned place preference
      (CPP) induced by 10 mg/kg cocaine in C56BL/6J mice were assessed in two
      independent experiments. To this end, half of the mice were singly housed with a
      running wheel at 28 days of age for 10 weeks prior to psychopharmacological
      tests, during which housing conditions did not change, and the other half of mice
      were housed without running wheel. In Experiment 1, prior to initiating
      sensitization, psychomotor activity on the two first drug-free once-daily
      sessions was not affected by wheel-running. This was also found for the acute
      psychomotor-activating effect of cocaine on the first sensitization session.
      Psychomotor sensitization readily developed over the 9 following once-daily
      sessions in mice housed without wheel, whereas it was inhibited in mice housed
      with a wheel. However, that difference did not transfer to post-sensitization
      conditioned activity. In contrast with the sensitization results, mice housed
      with a wheel still expressed a clear-cut CPP which did not extinguish differently
      from that of the other group, a result in disaccord with previous studies
      reporting either an attenuating or an increasing effect of wheel-running on
      cocaine-induced conditioned reward. The available results together indicate that
      interactions between wheel-running and cocaine effects are far from being
      satisfactorily characterized.

PMID- 24434306
TI  - Ferroelectric properties of composites containing BaTiO3 nanoparticles of various
      sizes.
AB  - Size effects, including the occurrence of superparaelectric phases associated
      with small scale, are a significant research topic for ferroelectrics. Relevant
      phenomena have been explored in detail, e.g. for homogeneous, thin ferroelectric
      films, but the related effects associated with nanoparticles are usually only
      inferred from their structural properties. In contrast, this paper describes all
      the steps and concepts necessary for the direct characterization and quantitative
      assessment of the ferroelectric properties of as-synthesized and as-received
      nanoparticles. The method adopted uses electrical polarization measurements on
      polymer matrix composites containing ferroelectric nanoparticles. It is applied
      to ten different BaTiO3 particle types covering a size range from 10 nm to 0.8
      MUm. The influence of variations of particle characteristics such as
      tetragonality and dielectric constant is considered based on measurements of
      these properties. For composites containing different particle types a clearly
      differing polarization behaviour is found. For decreasing particle size,
      increasing electric field is required to achieve a given level of polarization.
      The size dependence of a measure related to the coercive field revealed by this
      work is qualitatively in line with the state of the knowledge for ferroelectrics
      having small dimensions. For the first time, such results and size effects are
      described based on data from experiments on collections of actual nanoparticles.

PMID- 24434307
TI  - Language and social functioning in children and adolescents with epilepsy.
AB  - Individuals with epilepsy have difficulties with social function that are not
      adequately accounted for by seizure severity or frequency. This study examined
      the relationship between language ability and social functioning in 193 children
      with epilepsy over a period of 36months following their first recognized seizure.
      The findings show that children with persistent seizures have poorer language
      function, even at the onset of their seizures, than do their healthy siblings,
      children with no recurrent seizures, and children with recurrent but not
      persistent seizures. They continue to demonstrate poorer language function
      36months later. This poor language function is associated with declining social
      competence. Intervention aimed at improving social competence should include
      consideration of potential language deficits that accompany epilepsy and social
      difficulty. 

PMID- 24434308
TI  - Variables associated with emergency department and/or unplanned hospital
      utilization for children with epilepsy.
AB  - In the United States, approximately one million people are evaluated annually in
      an emergency department (ED) for the diagnosis of a seizure or epilepsy. The
      highest percentages of these patients are less than five years of age. No studies
      have been performed on assessing potential variables associated with recurrent ED
      visits and/or unplanned hospitalizations for children with epilepsy.
      Institutional review board approval from Nationwide Children's Hospital was
      obtained prior to study initiation. An accountable care organization (ACO),
      Partner for Kids (PFK), database was searched for patients with the highest and
      the lowest number of ED visits and/or unplanned hospitalizations from 2007
      through 2011 using ICD-9 codes of 345.xx and 780.39. The patients were stratified
      into a high and a low utilizer group. The total number of visits and their
      associated health care costs were noted for each patient. In total, 120 patients
      were included for review. Information on the total number of no-shows to
      outpatient neurology clinic visits and telephone calls to neurology triage
      nursing was noted. A chart review was performed by a pediatric epileptologist to
      determine if each individual patient was an appropriate candidate for an
      emergency seizure treatment. The dose of emergency seizure medication was cross
      checked to the patient's actual dose during the time of ED or hospital
      presentation to determine if the dose given was high, low, or accurate based on
      dosing recommendations. Multivariable logistic regression was used to test the
      effects of factors. When controlling for other factors, patients who were given
      an incorrect or no emergency seizure dosing had a high probability of having
      multiple ED visits/unplanned hospitalizations compared with patients who were
      given correct dosing (odds ratio=11.28, 95% CI of odds ratio=(2.42, 52.63), p
      value<0.01 (p=0.0021)). Using a similar model, patients who experienced a higher
      number of no-shows to clinic visits had a higher probability of having multiple
      ED visits/unplanned hospitalizations (odds ratio=5.73 per 1 more number of no
      show, 95% CI of odds ratio=(1.78, 18.44), p value<0.01 (p=0.0034)). Future
      studies are planned to target these risk factors with the goal of decreased ED
      and/or hospital utilization for children with epilepsy. 

PMID- 24434309
TI  - Memory consolidation in children with epilepsy: does sleep matter?
AB  - INTRODUCTION: Children with epilepsy have frequent sleep disturbance and
      challenges in learning and memory. There is little research on the consolidation
      of memory during sleep in this population. The goal of this pilot study was to
      determine whether children with epilepsy are able to consolidate memories better
      after a sleep versus wake period as has been demonstrated in typically developing
      children. METHODS: This study was a prospective evaluation of children with
      epilepsy to determine if sleep improved episodic memory (using word lists) as
      compared with memory following a wake period of similar duration. The study was
      conducted in patients in the Epilepsy Monitoring Unit at a single academic health
      science center. In the sleep recall condition, the learning trials were presented
      in the evening, and delayed recall of the words was tested in the morning. In the
      wake condition, the learning took place in the morning, and the delayed recall
      took place later in the day. Subjects wore an actigraph to evaluate sleep/wake
      patterns. Data regarding the children's epilepsy, antiepileptic medications, and
      frequency of interictal epileptiform discharges were also documented. RESULTS:
      Ten children (agd 8-17years) participated in the study. For the entire sample,
      recall after sleep was better than recall after awake (p=0.03), and 7 of the 10
      children showed this effect. However, reanalyses removing an outlier showed no
      difference between the two recall conditions. The mean number of interictal
      epileptiform discharges was 8.8 during the recall after sleep and 7.8 during the
      recall after awake. Three children had seizures during the evaluation.
      CONCLUSION: In this pilot study, we demonstrated that a small cohort of children
      with epilepsy, with similar interictal epileptiform discharges during sleep and
      wake, showed no advantage in memory for a word list after a period of sleep than
      after a period of being awake. This finding requires further study in a larger
      cohort. Poor memory consolidation during sleep may contribute to the cognitive
      deficits in children with epilepsy.

PMID- 24434310
TI  - Aquaporin, forward osmosis and biomimetic membranes.
AB  - Aquaporin attracted attention not only of physiologists and biophysicists, but
      also of chemical engineers. Here we critically analyze a paper describing
      aquaporin-based artificial membranes, suggested for forward osmosis-based water
      purification (Wang et al. 2012, Small 8, pp. 1185-1190). Related papers published
      later by the same group are also discussed. We indicate recently developed
      general approach to describe membrane transport, membrane permeability and
      selectivity, which is applicable for forward osmosis. In addition, we also
      mention our papers describing simple nitrocellulose-based membranes, which have
      selective aqueous channels without proteins, but successfully imitate many
      properties of biomembranes. 

PMID- 24434312
TI  - Translational immunology in Asia Oceania.

PMID- 24434313
TI  - Role of apoptosis-inducing factor (Aif) in the T cell lineage.
AB  - Multiple checkpoints regulating finely balanced death-versus-survival decisions
      characterize both thymic development and peripheral homeostasis of T lymphocytes.
      While exploring the mechanisms of T cell death involved at various stages during
      the life of a T cell, we have observed and reported a variety of non-redundant
      roles for apoptosis inducing factor (Aif), a mitochondrial flavoprotein. Aif is
      ubiquitously expressed in all cell lineages and functions as an NADH oxidase in
      its mitochondrial location. It is released following the mitochondrial death
      signals, whereupon it translocates to the nucleus, binds to DNA and causes large
      scale DNA fragmentation. During T cell development, Aif is important for
      developing thymocytes to navigate the double negative (DN)3 to DN4 transition
      (beta-selection), via its oxidoreductase property which protects the rapidly
      proliferating cells from death due to reactive oxygen species (ROS). In
      peripheral mature T cells, Aif deficiency leads to an increased susceptibility of
      T cell blasts to activation induced cell death (AICD), possibly mediated by its
      antioxidant function, and decreased sensitivity to neglect-induced death (NID).
      Thus, Aif seems to have pro-apoptotic and anti-apoptotic roles in the same
      lineage in different contexts and at different stages. Surprisingly, in the
      closely related B lymphocyte lineage, Aif deficiency does not result in any
      abnormality. These findings generate the possibility of specific T cell
      dysfunction in human disease caused by Aif deficiency, as well as in
      mitochondriopathies due to other causes. Also, these data raise questions
      regarding the basis of lineage-specific consequences of the
      dysfunction/deficiency of apparently ubiquitous molecules. 

PMID- 24434314
TI  - Modulation of autoimmune diseases by interleukin (IL)-17 producing regulatory T
      helper (Th17) cells.
AB  - Following the discovery of interleukin (IL)-17 producing T helper (Th17) cells as
      a distinct lineage of CD4+ T helper cells it became clear that these cells play
      an important role in the host defense against extracellular fungal and bacterial
      pathogens and participate in the pathogenesis of multiple inflammatory and
      autoimmune disorders. Depending on the microenvironment, Th17 cells can alter
      their differentiation programme ultimately giving rise to either protective or
      pro-inflammatory pathogenic cells. We found that besides the conventional in
      vitro protocol for Th17 differentiation by transforming growth factor-beta (TGF
      beta) plus IL-6 cytokines, a combination of IL-23 plus IL-6 can also induce Th17
      cells. The Th17 cells induced by IL-23 plus IL-6 (termed as effector Th17, Teff17
      cells) are pathogenic upon adoptive transfer into non-obese diabetic (NOD) mice
      contributing to the development of type 1 diabetes (T1D) while cells induced by
      TGF-beta plus IL-6 (termed as regulatory T cells, Treg17 cells) are non
      pathogenic and regulatory, and suppressed the pathogenic T cells in T1D. These
      cells differentially expressed a number of cytokines where Teff17 cells exhibited
      an increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL
      22 whereas Treg17 cells demonstrated increased expression of IL-21 and
      immunosuppressive cytokine IL-10. Differentiation of Th17 cells is controlled by
      a transcription factor, RORgammaT although these cells also express variable
      levels of T-bet and FoxP3 transcription factors. This points to a dual functional
      role of Th17 subsets in autoimmune diseases particularly T1D. We suggest that
      similar to conventional regulatory T cells (Treg), induction of regulatory Treg17
      cells could play an important role in modulating and preventing certain
      autoimmune diseases. 

PMID- 24434315
TI  - T cell ageing: effects of age on development, survival & function.
AB  - Age associated decline of the immune system continues to be a major health
      concern. All components of innate and adaptive immunity are adversely affected to
      lesser or greater extent by ageing resulting in an overall decline of
      immunocompetence. As a result in the aged population, there is increased
      susceptibility to infection, poor responses to vaccination, and increased
      incidence of autoreactivity. There is an increasing focus on the role of T cells
      during ageing because of their impact on the overall immune responses. A steady
      decline in the production of fresh naive T cells, more restricted T cell receptor
      (TCR) repertoire and weak activation of T cells are some of the effects of
      ageing. In this review we summarize our present understanding of the effects of
      ageing on naive CD4 T cells and potential approaches for therapeutic
      interventions to restore protective immunity in the aged population. 

PMID- 24434316
TI  - Targeting toll-like receptor signaling as a novel approach to prevent ocular
      infectious diseases.
AB  - Toll-like receptors (TLRs) play a key role in the innate immune response to
      invading pathogens. Thus, their discovery has opened up a wide range of
      therapeutic possibilities for various infectious and inflammatory diseases. In
      the last several years, extensive research efforts have provided a considerable
      wealth of information on the expression and function of TLRs in the eye, with
      significant implications for better understanding of pathogenesis of infectious
      eye diseases affecting the cornea, uvea, and the retina. In this review, by using
      bacterial keratitis and endophthalmitis as examples, we discuss the possibilities
      of targeting TLR signaling for the prevention or treatment of ocular infectious
      diseases. 

PMID- 24434317
TI  - T cell recognition of non-peptidic antigens in infectious diseases.
AB  - The immune system has evolved to recognize a wide range of antigenic molecules of
      self and non-self origin. The stimulatory antigens form complexes with antigen
      presenting molecules and directly interact with the T cell receptor (TCR).
      Peptidic antigens associate with major histocompatibility complex (MHC) molecules
      and therefore, are indicated as MHC-restricted. Non-peptidic antigens do not bind
      to MHC molecules and are presented by other classes of antigen-presenting
      molecules. These non-MHC restricted antigens include glycolipid molecules,
      phosphorylated metabolites of the mevalonate pathway and vitamin B2 precursors. T
      cells specific for non-peptidic antigens have important roles in host defense
      against infections, autoimmunity, allergies and tumour immunosurveillance. Hence,
      understanding the molecular interactions between the antigen presenting cell
      (APC) and the T cells with non-peptidic specificity is of great relevance. Here,
      we review current knowledge of this type of T cells, their TCR repertoire, the
      structural aspects of recognized antigens, the mode of antigen recognition, and
      their function with special emphasis on their role in infectious diseases. 

PMID- 24434319
TI  - Sialic acids siglec interaction: a unique strategy to circumvent innate immune
      response by pathogens.
AB  - Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal
      residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like
      lectins (siglecs) are generally expressed on various immune cells. They
      selectively recognize different linkage-specific sialic acids and undertake a
      variety of cellular functions. Many pathogens either synthesize or acquire sialic
      acids from the host. Sialylated pathogens generally use siglecs to manipulate the
      host immune response. The present review mainly deals with the newly developed
      information regarding mechanism of acquisition of sialic acids by pathogens and
      their biological relevance especially in the establishment of successful
      infection by impairing host innate immunity. The pathogens which are unable to
      synthesize sialic acids might adsorb these from the host as a way to engage the
      inhibitory siglecs. They promote association with the immune cells through sialic
      acids-siglec dependent manner. Such an association plays an important role to
      subvert host's immunity. Detailed investigation of these pathways has been
      discussed in this review. Particular attention has been focused on Pseudomonas
      aeruginosa (PA) and Leishmania donovani. 

PMID- 24434318
TI  - Antiviral macrophage responses in flavivirus encephalitis.
AB  - Mosquito-borne flaviviruses are a major current and emerging threat, affecting
      millions of people worldwide. Global climate change, combined with increasing
      proximity of humans to animals and mosquito vectors by expansion into natural
      habitats, coupled with the increase in international travel, have resulted in
      significant spread and concomitant increase in the incidence of infection and
      severe disease. Although neuroinvasive disease has been well described for some
      viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus
      (WNV), others such as dengue virus (DENV) have recently displayed an emerging
      pattern of neuroinvasive disease, distinct from the previously observed,
      systemically-induced encephalomyelopathy. In this setting, the immune response is
      a crucial component of host defence, in preventing viral dissemination and
      invasion of the central nervous system (CNS). However, subversion of the anti
      viral activities of macrophages by flaviviruses can facilitate viral replication
      and spread, enhancing the intensity of immune responses, leading to severe immune
      mediated disease which may be further exacerbated during the subsequent infection
      with some flaviviruses. Furthermore, in the CNS myeloid cells may be responsible
      for inducing specific inflammatory changes, which can lead to significant
      pathological damage during encephalitis. The interaction of virus and cells of
      the myeloid lineage is complex, and this interaction is likely responsible at
      least in part, for crucial differences between viral clearance and pathology.
      Recent studies on the role of myeloid cells in innate immunity and viral control,
      and the mechanisms of evasion and subversion used by flaviviruses are rapidly
      advancing our understanding of the immunopathological mechanisms involved in
      flavivirus encephalitis and will lead to the development of therapeutic
      strategies previously not considered. 

PMID- 24434320
TI  - Genomic architecture of HIV-1 infection: current status & challenges.
AB  - Studies on host genomics have revealed the existence of identifiable HIV-1
      specific protective factors among infected individuals who remain naturally
      resistant viraemia controllers with little or no evidence of virus replication.
      These factors are broadly grouped into those that are immune associated (MHC,
      chemokines, cytokines, CTLs and others), linked to viral entry (chemokine co
      receptors and ligands), act as post-entry restriction elements (TRIM5a, APOBEC3)
      and those associated with viral replication (cytokines and others). These
      features have been identified through multiple experimental approaches ranging
      from candidate gene approaches, genome wide association studies (GWAS),
      expression analysis in conjunction with functional assays in humans to primate
      based models. Several studies have highlighted the individual and population
      level gross differences both in the viral clade sequences as well as host
      determined genetic associations. This review collates current information on
      studies involving major histocompatibility complex (MHC) as well as non MHC genes
      in the context of HIV-1 infection and AIDS involving varied ethnic groups.
      Special focus of the review is on the genetic studies carried out on the Indian
      population. Further challenges with regard to therapeutic interventions based on
      current knowledge have been discussed along with discussion on documented cases
      of stem cell therapy and very early highly active antiretroviral therapy (HAART)
      interventions. 

PMID- 24434321
TI  - The enduring tale of T cells in HIV immunopathogenesis.
AB  - HIV continues to be a major health problem worldwide even today. Owing to the
      intricate nature of its interactions with the immune system, HIV has remained an
      enigma that cleverly utilizes the host machinery to survive. Its ability to evade
      the host immune system, at both levels, innate and adaptive, allows the pathogen
      to replicate and transmit from one host to another. It has been shown that HIV
      has multipronged effects especially on the adaptive immunity, with CD4+ T cells
      being the worst affected T cell populations. Various analyses have revealed that
      the exposure to HIV results in clonal expansion and excessive activation of the
      immune system. Also, an abnormal process of differentiation has been observed
      suggestive of an alteration and blocks in the maturation of various T cell
      subsets. Additionally, HIV has shown to accelerate immunosenescence and
      exhaustion of the overtly activated T cells. Apart from causing phenotypic
      changes, HIV has adverse effects on the functional aspect of the immune system,
      with evidences implicating it in the loss of the capacity of T cells to secrete
      various antiviral cytokines and chemokines. However, there continues to be many
      aspects of the immunopathogenesis of HIV that are still unknown and thus require
      further research to convert the malaise of HIV into a manageable epidemic. 

PMID- 24434322
TI  - Immunological mechanisms of hepatitis B virus persistence in newborns.
AB  - Chronic hepatitis B virus (HBV) infection affects millions of people worldwide
      and about a half million people die every year. India represents the second
      largest pool of chronic HBV infection worldwide with an estimated 40 million
      infected people. The prevalence of chronic HBV infection in pregnant women is
      shown to be 0.82 per cent with the risk of mother-to-child vertical transmission.
      Hepatitis B e antigen (HBeAg) positivity indicates replicative form of HBV which
      may play a role in immunotolerance in utero by crossing the placenta. In case of
      HBeAg positivity and high viral load of mother, HBV immunoglobulin is preferably
      given along with HBV vaccination. Antiviral therapy is recommended for use in the
      third trimester of pregnancy to reduce the perinatal transmission of HBV,
      however, use of antiviral therapy should be individualized during pregnancy.
      Chronic HBV infection in neonates is linked with strong presence of Tregs (T
      regulatory cells) and defective CD8 T cells pool to produce interferon (IFN)
      gamma. T cell receptor (TCRzeta) chain defects were also associated with
      decreased CD8 T cell dysfunction. Decreased TCRzeta expression could be due to
      persistent intrauterine exposure of the viral antigens early in embryonic
      development leading to immune tolerance to HBV antigens in the newborns positive
      for hepatitis B surface antigen (HBsAg+ve). Therefore, due to HBV infection, T
      cell tolerance to HBV-antigen may probably leave the newborn as a chronic
      carrier. However, HBV vaccination may have benefits in restoring acquired
      immunity and better production of HBV specific antibodies. 

PMID- 24434323
TI  - Inflammation & autoimmunity in human ageing: dendritic cells take a center stage.
AB  - Dendritic cells (DCs) play an important role in both immunological tolerance and
      immunity as well as in pro- and anti-inflammatory responses. Upon uptake of
      apoptotic cells and apoptotic bodies, DCs degrade self antigens from them and
      induce anti-inflammatory response and T regulatory (Treg) cells resulting in the
      maintenance of tolerance to self antigens. Ageing is characterized by progressive
      immunodeficiency, inflammation, and autoimmunity. In this paper we will review
      the role of DCs in inflammation and autoimmunity in human ageing and will
      highlight the observations that DCs from aged humans display impairment in their
      capacity to uptake apoptotic cells, and paradoxically induce proinflammatory
      response and increased reactivity to self antigen (DNA). DNA from aged is
      hypomethylated and hypomethylation is associated with increased immunogenecity of
      self DNA. 

PMID- 24434324
TI  - Temporal cytokine expression and the target organ attributes unravel novel
      aspects of autoimmune arthritis.
AB  - Susceptibility to autoimmunity is determined by multiple factors. Defining the
      contribution of the quantitative versus qualitative aspects of antigen-directed
      immune responses as well as the factors influencing target organ susceptibility
      is vital to advancing the understanding of the pathogenesis of autoimmunity. In a
      series of studies, we have addressed these issues using the adjuvant-induced
      arthritis (AA) model of human rheumatoid arthritis (RA). Lewis rats are
      susceptible to AA following immunization with heat-killed Mycobacterium
      tuberculosis H37Ra, whereas Wistar-Kyoto (WKY) rats of the same MHC (major
      histocompatibility complex) haplotype are resistant. Comparative studies on these
      and other susceptible/resistant rodent strains have offered interesting insights
      into differential cytokine responses in the face of comparable T cell
      proliferative response to the disease relevant antigens. Study of the cytokine
      kinetics have also permitted validation of the disease-protective versus disease
      aggravating effects of specific cytokines by treatment of rats/mice with those
      cytokines at different phases of the disease. In regard to the target organ
      attributes, the migration of arthritogenic leukocytes into the joints; the
      expression of mediators of inflammation, angiogenesis, and tissue damage; the
      role of vascular permeability; and the characteristics of vascular endothelial
      cells have been examined. Further, various inhibitors of angiogenesis are
      effective in suppressing arthritis. Taken together, the differential cytokine
      responses and unique attributes of the target organ have revealed novel aspects
      of disease susceptibility and joint damage in AA. The translation of this basic
      research in animal models to RA patients would not only advance our understanding
      of the disease process, but also offer novel avenues for immunomodulation of this
      disease. 

PMID- 24434326
TI  - Lipidated promiscuous peptide augments the expression of MHC-II molecules on
      dendritic cells and activates T cells.
AB  - BACKGROUND & OBJECTIVES: In spite of the fact that BCG is the most widely used
      vaccine, tuberculosis (TB) continues to be a major killer disease in TB-endemic
      regions. Recently, many emerging evidences from the published literature indicate
      the role of environmental mycobacteria in blocking the processing and
      presentation of BCG antigens and thereby impairing with suboptimal generation of
      protective T cells. To surmount this problem associated with BCG, we constructed
      a novel lipopeptide (L91) by conjugating a promiscuous peptide consisting of CD4
      + T-helper epitope of sequence of 91-110 of 16 kDa antigen of Mycobacterium
      tuberculosis to Pam2Cys, an agonist of Toll-like receptor-2. METHODS: Mice were
      immunized subcutaneously with 20 nmol of L91, followed by a booster with 10 nmol,
      after an interval of 21 days of primary immunization. Animals were sacrificed
      after seven days of post-booster immunization. L91 induced immune response was
      characterized by the expression of MHC-II and CD74 on the surface of dendritic
      cells (DCs) by flowcytometry. Cytokines (IL-4, IL-10, IFN-gamma) secretion and
      anti-peptide antibodies were measured by ELISA. RESULTS: Self-adjuvanting
      lipopeptide vaccine (L91) was directly bound to MHC-II molecules and without
      requiring extensive processing for its presentation to T cells. It stimulated and
      activated dendritic cells and augmented the expression of MHC-II molecules.
      Further, it activated effector CD4 T cells to mainly secrete interferon (IFN)
      gamma but not interleukin (IL)-4 and IL-10. L91 did not elicit anti-peptide
      antibodies. INTERPRETATION & CONCLUSIONS: The findings suggest that L91 evokes
      maturation and upregulation of MHC class II molecules and promotes better antigen
      presentation and, therefore, optimum activation of T cells. L91 mainly induces
      effector Th1 cells, as evidenced by predominant release of IFN-gamma,
      consequently can mount favourable immune response against M. tuberculosis . As
      L91 does not provoke the generation of anti-peptide antibodies, there is no fear
      of the efficacy of the vaccine being neutralized by pre-existing anti
      mycobacterial antibodies in TB-endemic population. In conclusion, L91 may be
      considered as a future potential candidate vaccine against TB.

PMID- 24434325
TI  - Bugs & us: the role of the gut in autoimmunity.
AB  - Rheumatoid arthritis (RA) is a multifactorial disease and requires interaction
      between genetic and environmental factors for predisposition. The presence of
      bacterial DNA of the gut residing commensals in synovium as well as dysbiosis of
      certain commensal bacteria in faecal samples of RA patients as compared to
      controls suggest a significant role of the gut flora in pathogenesis of RA. The
      gut commensals are involved in host immune development and function suggesting
      they might be critical epigenetic factors modifying autoimmune diseases like RA.
      This raises the question if gut-derived commensal can be exploited to generate a
      biomarker profile along with genetic factors to define individuals at risk.
      Genomic wide association studies have confirmed the HLA (human leukocyte antigen)
      class II genes as the strongest risk factor for predisposition to RA. HLA-DQ8 and
      DRB1FNx010401 molecules predispose to develop arthritis while DRB1FNx010402
      provides protection. Interaction between host genetic factors like major
      histocompatibility complex (MHC) and gut microbiota and its impact on the
      development of RA is difficult to study in humans due to high variability in the
      genetic factors and diet. Animal models provide a means to study the molecular
      basis of pathogenesis thereby providing a basis for developing therapeutic
      strategies. Using transgenic mice expressing RA-associated and resistant HLA
      genes, we have developed a collagen-induced arthritis (CIA) model that shares
      similarities with human disease in sex-bias, autoantibody profile and phenotype.
      Studies in transgenic mice suggest that arthritis-susceptibility may be
      associated with dysbiosis in the gut microbiome. Studies in animal models
      underscore the impact of the gut flora in extra-intestinal diseases. Exploring
      the role of gut microbes will significantly advance our understanding of RA
      pathogenesis and may further help develop strategies for mucosal modulation of
      RA. 

PMID- 24434327
TI  - Allogenicity & immunogenicity in regenerative stem cell therapy.
AB  - The development of regenerative medicine relies in part on the capacity of stem
      cells to differentiate into specialized cell types and reconstitute tissues and
      organs. The origin of the stem cells matters. While autologous cells were
      initially the preferred ones the need for "off the shelf" cells is becoming
      prevalent. These cells will be immediately available and they originate from
      young non diseased individuals. However their allogenicity can be viewed as a
      limitation to their use. Recent works including our own show that allogenicity of
      stem cell can be viewed as on one hand detrimental leading to their elimination
      and on the other hand beneficial through a paracrine effect that can induce a
      local tissue regenerative effect from endogenous stem cells. Also their immune
      modulatory capacity can be harnessed to favor regeneration. Therefore the immune
      phenotype of stem cells is an important criteria to be considered before their
      clinical use. Immuno monitoring of the consequences of their in vivo injection
      needs to be taken into account. Transplantation immunology knowledge will be
      instrumental to enable the development of safe personalized regenerative stem
      cell therapy. 

PMID- 24434328
TI  - Targeting gamma delta T cells for cancer immunotherapy: bench to bedside.
AB  - gammadelta T lymphocytes represent a minor subset of peripheral blood in humans
      (<10%). gammadelta T cells expressing Vgamma9Vdelta2 T cell receptor recognise
      the endogenous pool of isopentenyl pyrophosphate (IPP) that is overproduced in
      cancer cells as a result of dysregulated mevalonate pathway. Aminobisphosphonates
      increase the endogenous pool of IPP in cells by blocking the enzyme farnesyl
      pyrophosphate synthase (FPPS) of the mevalonate pathway. Activated gammadelta T
      cells release copious amounts of interferon (IFN)-gamma and tumour necrosis
      factor (TNF)-alpha and exhibit potent anti-tumour activity. Combination of
      gammadelta T cells with therapeutic monoclonal antibodies can efficiently mediate
      antibody dependent cellular cytotoxicity against tumours. These features makes
      gammadelta T cells attractive mediator of cancer immunotherapy. We review here,
      the basic properties and importance of gammadelta T cells in tumour immunity, and
      highlight the key advances in anti-tumour effector functions of gammadelta T
      cells achieved over the last few years and also summarize the results of the
      clinical trials that have been done till date. Future immunotherapeutic approach
      utilizing gammadelta T cells holds considerable promise for treatment of
      different types of cancer. 

PMID- 24434329
TI  - Approaches to the treatment of disease induced by chikungunya virus.
AB  - Chikungunya virus, a re-emerging mosquito-borne alphavirus, causes fever, rash
      and persistent arthralgia/arthritis in humans. Severe outbreaks have occurred
      resulting in infections of millions of people in Southeast Asia and Africa.
      Currently there are no antiviral drugs or vaccines for prevention and treatment
      of chikungunya infections. Herein we report the current status of research on
      antiviral drugs and vaccines for chikungunya virus infections. 

PMID- 24434330
TI  - Success of antiviral therapy in chronic hepatitis C infection relates to
      functional status of myeloid dendritic cells.
AB  - Chronic hepatitis C infection poses a major global health predicament and appears
      to be potent threat to mankind. The treatment in wide use is interferon/ribavirin
      combination therapy which is generally effective in about 60-70 per cent of
      patients carrying genotype 3 and causes significant morbidity. The response to
      therapy is largely guided by limited number of factors such as genotype of virus,
      rapid virological response, ethnicity, pre-therapy viral load, etc. While
      involvement of host genetic factors has been a major focus of research in playing
      an important role in the outcome of disease, the role of immune system cannot be
      marginalized. Poor cellular trafficking and suboptimal T cell responses in liver,
      the hall marks of chronic hepatitis C virus infection, might be attributed to
      defective antigen presentation. Various immunological factors, both innate and
      adaptive, play role in the pathogenesis of the disease and become dysfunctional
      in active disease. Recent reports suggest the major impact of functional and
      numerical status of dendritic cells in deciding the fate of antiviral therapy. In
      this review we take a look at the involvement of dendritic cells in playing an
      important role in the response to therapy. 

PMID- 24434331
TI  - Novel adjuvants & delivery vehicles for vaccines development: a road ahead.
AB  - The pure recombinant and synthetic antigens used in modern day vaccines are
      generally less immunogenic than older style live/attenuated and killed whole
      organism vaccines. One can improve the quality of vaccine production by
      incorporating immunomodulators or adjuvants with modified delivery vehicles viz.
      liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from
      alum, being used as gold standard. Adjuvants are used to augment the effect of a
      vaccine by stimulating the immune system to respond to the vaccine, more
      vigorously, and thus providing increased immunity to a particular disease.
      Adjuvants accomplish this task by mimicking specific sets of evolutionary
      conserved molecules which include lipopolysaccharides (LPS), components of
      bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and
      unmethylated CpG dinucleotide containing DNA. This review provides information on
      various vaccine adjuvants and delivery vehicles being developed to date. From
      literature, it seems that the humoral immune responses have been observed for
      most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides
      have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL(r) have
      elicited Th1 responses, and virus-like particles (VLPs), non-degradable
      nanoparticle and liposomes have also generated cellular immunity. Such vaccine
      components have also been evaluated for alternative routes of administration with
      clinical success reported for intranasal delivery of viral-vectors and
      proteosomes and oral delivery of VLP vaccines. 

PMID- 24434334
TI  - ET-1/NO: a controversial target for myocardial ischemia-reperfusion injury.

PMID- 24434333
TI  - Probiotics as efficient immunopotentiators: translational role in cancer
      prevention.
AB  - Accumulating evidences indicate that some diseases are triggered by abnormalities
      of the gut microbiota. Among these, immune-related diseases can be the promising
      targets for probiotcs. Several studies have proved the efficacy of probiotics for
      preventing such diseases including cancers, infections, allergies, inflammatory
      bowel diseases and autoimmune diseases. Lactobacillus casei strain Shirota (LcS)
      is one of the most popular probiotics, benefits of which in health maintenance
      and disease control have been supported by several science-based evidences. This
      review summarizes human clinical trials with this probiotic against cancer
      development and also discusses the possible immunomodulatory mechanisms by which
      LcS exerts anti-cancer activity. 

PMID- 24434332
TI  - Cellular immune therapy for viral infections in transplant patients.
AB  - Stem cell and organ transplantation are considered as the major advances of
      modern medicine. Unfortunately the success of transplantation is limited by its
      toxicity and infectious complications as a result of profound immunosuppression.
      Viral infections are an extremely common and predictable problem in these
      patients. Antiviral drugs given either prophylactically or as early therapy for
      patients with detectable viral loads appear to be an effective strategy for
      reducing viral infections. However, long-term treatment with these drugs is
      associated with significant toxicity, expense and the appearance of drug
      resistant virus isolates ultimately resulting in treatment failure. Over the last
      few years, there is increasing evidence that cellular immune therapies can
      reverse the outgrowth of haematological malignancies and can also provide
      therapeutic benefit against lethal viral infections. While the expansion and
      adoptive transfer of virus-specific T-cells from the healthy donor can be an
      effective strategy to control viral replication, this is not possible when donors
      are seronegative or are subsequently inaccessible. Recent studies have
      demonstrated successful expansion of virus-specific T-cells from seropositive
      stem cell transplant recipients of a seronegative graft with active virus disease
      and the long term reconstitution of protective anti-viral immunity following
      their adoptive transfer back into the patients. Furthermore, this
      immunotherapeutic strategy has also been extended for multiple pathogens
      including cytomegalovirus, Epstein-Barr virus, adenovirus and BK polyoma-virus.
      This approach can be employed to rapidly expand multiple pathogens-specific T
      cells that can be used for adoptive immunotherapy. Finally, new assays to monitor
      T cell immunity have been developed which will allow to identify the high risk
      transplant patients who may develop virus-associated complications post
      transplantation and can be given adoptive T cell therapy prophylactically. 

PMID- 24434339
TI  - Abstracts of the 11th Annual World Congress on Insulin Resistance, Diabetes &
      Cardiovascular Disease (WCIRDC).

PMID- 24434335
TI  - Strain- and age-dependent hippocampal neuron sodium currents correlate with
      epilepsy severity in Dravet syndrome mice.
AB  - Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic
      encephalopathy of infancy that exhibits variable clinical severity. We utilized a
      heterozygous Scn1a knockout (Scn1a(+/-)) mouse model of Dravet syndrome to
      investigate the basis for phenotype variability. These animals exhibit strain
      dependent seizure severity and survival. Scn1a(+/-) mice on strain 129S6/SvEvTac
      (129.Scn1a(+/-)) have no overt phenotype and normal survival compared with
      Scn1a(+/-) mice bred to C57BL/6J (F1.Scn1a(+/-)) that have severe epilepsy and
      premature lethality. We tested the hypothesis that strain differences in sodium
      current (INa) density in hippocampal neurons contribute to these divergent
      phenotypes. Whole-cell voltage-clamp recording was performed on acutely
      dissociated hippocampal neurons from postnatal days 21-24 (P21-24) 129.Scn1a(+/-)
      or F1.Scn1a(+/-) mice and wild-type littermates. INa density was lower in
      GABAergic interneurons from F1.Scn1a(+/-) mice compared to wild-type littermates,
      while on the 129 strain there was no difference in GABAergic interneuron INa
      density between 129.Scn1a(+/-) mice and wild-type littermate controls. By
      contrast, INa density was elevated in pyramidal neurons from both 129.Scn1a(+/-)
      and F1.Scn1a(+/-) mice, and was correlated with more frequent spontaneous action
      potential firing in these neurons, as well as more sustained firing in
      F1.Scn1a(+/-) neurons. We also observed age-dependent differences in pyramidal
      neuron INa density between wild-type and Scn1a(+/-) animals. We conclude that
      preserved INa density in GABAergic interneurons contributes to the milder
      phenotype of 129.Scn1a(+/-) mice. Furthermore, elevated INa density in excitatory
      pyramidal neurons at P21-24 correlates with age-dependent onset of lethality in
      F1.Scn1a(+/-) mice. Our findings illustrate differences in hippocampal neurons
      that may underlie strain- and age-dependent phenotype severity in a Dravet
      syndrome mouse model, and emphasize a contribution of pyramidal neuron
      excitability. 

PMID- 24434340
TI  - Management of multivessel coronary artery disease.
AB  - Optimal management of multivessel disease (MVD) is a complex medical decision
      with significant prognostic implications. Despite the advent of clinical and
      angiographic scores to aid with treatment delineation, therapy for MVD must be
      individualized for each patient and his/her clinical presentation. Particularly
      among patients with MVD, the selection of coronary revascularization with
      percutaneous coronary intervention versus coronary artery bypass graft surgery
      versus guideline-directed medical therapy (GDMT) alone is a prognostically
      important decision. Several patient factors including clinical presentation,
      severity of coronary artery disease, presence of left ventricular dysfunction and
      other comorbidities, and the patient's personal preferences should guide the
      decision making process. In this review, we discuss the management of MVD with
      regards to decisions of revascularization versus GDMT alone, mode of
      revascularization, extent of revascularization (i.e., complete versus
      incomplete), the strategy of angiography- versus ischemia-guided
      revascularization, and MVD management in the setting of an acute coronary
      syndrome. 

PMID- 24434336
TI  - The dengue virus non-structural 1 protein: risks and benefits.
AB  - The dengue virus (DENV) non-structural 1 (NS1) protein plays a critical role in
      viral RNA replication and has a central position in DENV pathogenesis. DENV NS1
      is a glycoprotein expressed in infected mammalian cells as soluble monomers that
      dimerize in the lumen of the endoplasmic reticulum; NS1 is subsequently
      transported to the cell surface, where it remains membrane associated or is
      secreted into the extracellular milieu as a hexameric complex. During the last
      three decades, the DENV NS1 protein has also been intensively investigated as a
      potential target for vaccines and antiviral drugs. In addition, NS1 is the major
      diagnostic marker for dengue infection. This review highlights some important
      issues regarding the role of NS1 in DENV pathogenesis and its biotechnological
      applications, both as a target for the development of safe and effective vaccines
      and antiviral drugs and as a tool for the generation of accurate diagnostic
      methods. 

PMID- 24434341
TI  - Current state of percutaneous transcatheter mitral valve therapies.
AB  - Mitral valve regurgitation (MR) is a frequent condition usually associated with
      heart failure and reduced survival. Surgery remains the gold standard treatment
      but a significant number of patients are not optimal candidates due to age,
      comorbidities or poor left ventricular function. In this subgroup of patients
      transcatheter mitral interventions have emerged as an alternative to offer
      improvement of symptoms and increase survival. MitraClip (r) is the device with
      the largest clinical experience and it has been demonstrated to provide clinical
      benefit in selected patients. However, mitral apparatus is a complex scenario and
      there are several potential targets for improving mitral regurgitation. The aim
      of this paper was to review the current trnascatheter technology developed to
      treat MR. 

PMID- 24434342
TI  - The optimal treatment of STEMI: new pharmacological and device approaches.
AB  - Cardiovascular disease remains the leading cause of mortality worldwide. Many
      deaths are contributed to acute ST elevation myocardial infarction (STEMI).
      Recently, epidemiological studies have been shown reduction in STEMI related
      mortality over the last decade. This reduction has partially been attributed to
      new pharmacological and device advances that were utilized during STEMI
      treatment. The goal of this manuscript is to review new pharmacological and
      device approaches available in the treatment of STEMI patients. 

PMID- 24434343
TI  - Innovations in drug-eluting stents.
AB  - Coronary artery disease affects patients worldwide and is a major cause of
      morbidity and mortality. Historically, the treatment approach for patients with
      coronary syndromes has been surgical. In the 1970s, percutaneous balloon
      angioplasty was introduced, leading to creation of a new field of interventional
      cardiology, which allowed a non-surgical minimally invasive approach to treat
      patients with coronary artery disease. However, the major limitations of balloon
      angioplasty were acute vessel closure and later restenosis. The introduction of
      bare metal stents and then drug-eluting stents (DES) revolutionized the practice
      of interventional cardiology and allowed for safe treatment of increasingly
      complex coronary artery lesions. Although drug-eluting coronary stents improve
      patient outcomes, they still have limitations. These limitations may arise from
      delayed endothelialization, local vessel hypersensitivity and endothelial
      dysfunction secondary to the drug elution, the durable polymer coating, or the
      stent scaffold. This comprehensive review will discuss the evolution of
      intracoronary stents from their introduction to current utilization of DES as
      well as future research on bioabsorbable stents and polymers. 

PMID- 24434344
TI  - Targeted vascular drug delivery. A new day for an old way.
AB  - Local drug delivery for the treatment of vascular disease has been studied for
      many years. In coronary artery disease, drug eluting stents are routinely
      deployed. However, with concerns regarding late thrombosis, and clinical
      applications where stenting is not desirable, such as peripheral vascular
      disease, a new direction to "leave nothing behind" has emerged. In Europe,
      paclitaxel-coated balloons have shown promise in reducing restenosis in both
      peripheral and coronary applications. However, a number of technical, economic
      and regulatory limitations of the current devices have been identified. Local or
      targeted fluid delivery of drugs may offer a relatively simple solution. 

PMID- 24434345
TI  - Plasma brain derived neurotrophic factor levels and neuropsychological aspects of
      depressed patients treated with paroxetine.
AB  - AIM: Studies on major depressive disorders (MDD) pathophysiology show decreased
      blood levels of brain-derived neurotrophic factor (BDNF) that increase after
      antidepressant treatment. The link between BDNF levels and antidepressants is
      still controversial. In addiction, there is a relationship between MDD and
      concurrent cognitive function. Hippocampus is linked to memory and learning and
      BDNF is abundant in this area. For this reason we investigated the presence of
      any association between paroxetine treatment, BDNF levels and cognitive
      performances in depressed patients. METHODS: Sixteen patients with MDD were
      compared with a control group of 18 randomly selected healthy individuals. Blood
      samples were taken and clinical and neuropsychological assessments were performed
      at baseline and after two months of treatment. Plasma and serum BDNF levels were
      measured with the Elisa method. RESULTS: Plasma BDNF levels are lower in
      depressed patients and increased after treatment. No serum BDNF significant
      differences were found. Depressed patients showed a mild deficit in prose memory
      tests that reached normality after antidepressant treatment. No correlations were
      evidenced between patients plasma BDNF levels and cognitive results. CONCLUSION:
      To our knowledge this is one of the few studies on the effects of paroxetine
      treatment on plasma BDNF levels. We confirm literature data regarding the link
      between BDNF plasma levels, depression and antidepressant treatments. In
      addiction we found a specific cognitive deficit of depressed patients.

PMID- 24434346
TI  - The levels of adhesion molecules in essential thrombocythemia.
AB  - AIM: It is known that thrombocytosis is closely related to vascular complications
      and particularly thrombosis in essential thrombocytemia (ET) cases. The aim of
      this study is to investigate a possible correlation between adhesion molecules
      and vascular attacks as well as the relation of these molecules to the platelet
      count. METHODS: The study group consisted of 30 ET patients and 30 healthy
      controls subjects. Serum intracellular adhesion molecule-1 (ICAM-1), serum
      vascular adhesion molecule-1 (VCAM-1) and serum E-selectin levels were determined
      by ELISA method according to manufacturer's instructions. RESULTS: There were no
      significant differences between two groups with respect to levels of sICAM-1 and
      sE-selectin (P>0.05). The VCAM-1 levels and platelets were significantly higher
      in patients with ET compared to controls (P=0.000). Spearman's correlation
      analysis revealed that sVCAM-1 levels were correlated with platelet counts
      (r=0.574, P<0.001) CONCLUSION: High VCAM-1 level in ET and its correlation with
      the platelet count suggest that these may be a factor in vascular complications
      and thrombocytosis.

PMID- 24434347
TI  - Aortic valve stenosis and lipid-lowering therapy: the state of the art.
AB  - Aortic valve stenosis is the most common native valve disease and its most common
      cause in the United States and Europe is the calcification of a normal
      trileaflet. Recently, there is increasing evidence indicating that valve
      calcification has common underlying mechanisms with atherosclerosis. This
      connection raises interest in the potential efficacy of antiatherosclerosis
      medications in calcific valve stenosis (AS) therapy. Among them statins, are one
      of the most promising candidates, because of their pleiotropic effects. The aim
      of this review is to summarize and analyze the findings of contemporary studies
      and to discuss the rationale for statin usage in AS populations. 

PMID- 24434348
TI  - Does it exist a personality core of mental illness? A systematic review on core
      psychobiological personality traits in mental disorders.
AB  - AIM: Research investigating the relationship between mental disorders and
      personality traits leads to interesting results. Individuals affected by several
      mental disorders have been worldwide assessed according to the psychobiological
      model of personality. This review aims to explore which temperament and character
      traits are recurrent in mental disorders and to highlight what traits may be
      shared determinants or consequences of the expression of a mental disorder.
      METHODS: Systematic search of Medline database between 1998 and 2011 has been
      conducted to select the studies exploring the Temperament and Character Inventory
      (TCI) dimensions in the most relevant axis I psychiatric disorders. Of the 110
      studies that were retrieved, 88 met the inclusion/exclusion criteria and were
      analyzed. RESULTS: High HA (HA) and low self-directedness are recurrent and can
      be considered as a "personality core" regardless of the diagnosis. They may be
      risk factors and relapse-related, they can indicate incomplete remission or
      chronic course of mental disorders, and consistently influence patients'
      functioning. Furthermore, they can be modified by medications or psychotherapy
      and represent outcome predictors of treatments. CONCLUSION: This "core" may
      represent a personality diathesis to psychopathology. Relational environment can
      influence the development of both temperament and character, thus prevention of
      mental disorders should promote a positive development of these traits. Although
      further research is needed, psychotherapeutic interventions should be performed
      also considering that mental disorders could benefit from HA desensitization and
      SD reinforcement. Finally, these traits may be used to provide diagnostic,
      prognostic, quality of life and efficacy inferences on psychiatric treatments.

PMID- 24434349
TI  - Biomarkers of coagulation, fibrinolysis, endothelial function, and inflammation
      in arterialized venous blood.
AB  - Effects of venous blood arterialization on cardiovascular risk markers are still
      unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and
      endothelial function in arterialized compared with regular venous blood. Cubital
      venipunctures were obtained from 10 healthy volunteers. Arterialization was
      generated by 10 min heating of the contralateral hand. Concentrations of albumin,
      C-reactive protein (CRP), tissue-type plasminogen activator (t-PA), plasminogen
      activator inhibitor type 1 (PAI-1), and von Willebrand factor (vWF) were measured
      by validated assays. Concentrations of albumin, CRP, and vWF were significantly
      lower in arterialized than in venous blood (albumin: 43.8 g/l and 44.8 g/l, P =
      0.02). Differences in CRP and vWF became insignificant after adjusting for
      albumin. The endogenous thrombin potential (ETP) was significantly higher in
      arterialized than in venous blood (1929 nmol/l*min vs. 1872 nmol/l*min, P =
      0.02). Addition of the FXIIa inhibitor Corn Trypsin Inhibitor (CTI) prior to the
      thrombin generation test eliminated the ETP difference suggesting that hand
      heating activates the FXII-dependent coagulation pathway. 

PMID- 24434350
TI  - The utility of the Wells clinical prediction model and ventilation-perfusion
      scanning for pulmonary embolism diagnosis in pregnancy.
AB  - Pulmonary embolism is one of the leading causes of mortality in pregnancy in the
      Western world. No clinical prediction models have been validated in pregnancy. As
      a result, any pregnant woman presenting with signs possibly consistent with
      pulmonary embolism is investigated radiologically. This study investigates
      whether using clinical prediction models for pulmonary embolism in pregnancy
      should be pursued in future prospective trials. The aim of this study was to
      retrospectively evaluate the Wells clinical prediction model and ventilation
      perfusion scanning for pulmonary embolism in pregnancy. A retrospective study was
      performed on consecutive pregnant women who presented with suspected pulmonary
      emboli and underwent ventilation perfusion scanning at two tertiary institutions
      from 2007 until 2010. The clinical pretest probability was determined as likely
      or unlikely by two independent clinicians retrospectively using Wells-modified
      criteria. Scans were determined as normal, nondiagnostic or high probability for
      pulmonary emboli independently by two experienced radiologists. Disagreements
      were resolved by a third assessor independently. In 183 pregnant women, the
      pretest probability was determined as 'pulmonary emboli likely' in 76 (42%) and
      'pulmonary emboli unlikely' in 107 (58%) of women. Scans were of high probability
      in four (2%), nondiagnostic in six (3%) and normal in 173 (95%) of women. This
      gives the pretest probability using Wells-modified criteria a sensitivity of 100%
      [95% confidence interval (CI) 0.4-1.0] and a negative predictive value of 100%
      (95% CI 0.96-1.0). A structured clinical model such as modified Wells criteria
      may be useful in pregnancy, but further prospective evaluation is required. 

PMID- 24434351
TI  - Absence of GPR54 and TACR3 mutations in sporadic cases of idiopathic central
      precocious puberty.
AB  - BACKGROUND/AIMS: Kisspeptin (KISS1)/GPR54 (KISSR) signaling complex and
      neurokinin B (NKB)/NKB receptor (TACR3) signaling have been proposed as an
      integral part of the network coordinating GnRH release. GPR54 (KISS1R) and TACR3
      gene mutations have been described in cases of idiopathic hypogonadotrophic
      hypogonadism, while limited data exist on gain-of-function mutation in GPR54
      (KISS1R) gene causing idiopathic central precocious puberty (ICPP). No data on
      TACR3 mutations in ICPP have been described so far. The aim of this study was to
      elucidate the possible impact of GPR54 (KISS1R) and TACR3 mutations in ICPP.
      METHODS: PCR-amplified genomic DNA of 38 girls with ICPP was analyzed for GPR54
      and TACR3 gene mutations. RESULTS: No GPR54 or TACR3 mutations were found. The
      A/G coding sequence single nucleotide polymorphism (SNP) on the GPR54 gene (dbSNP
      ID: rs10407968) was found in 2 patients with ICPP. CONCLUSION: Our data indicate
      that GPR54 and TACR3 gene mutations are not a frequent cause of ICPP. The
      identified A/G synonymous SNP (dbSNP ID: rs10407968) located in exon 1 of the
      gene is not likely to have a pathogenic role in exon splicing and therefore in
      the premature initiation of puberty.

PMID- 24434352
TI  - Celastrol induces apoptosis of gastric cancer cells by miR-21 inhibiting PI3K/Akt
      NF-kappaB signaling pathway.
AB  - OBJECTIVE: Celastrol, a plant triterpene, has anticancer effects by increase of
      apoptosis. In the present study, the mechanism of celastrol on gastric cancer
      cell apoptosis was examined. METHODS: The effect of celastrol on PI3K/Akt and the
      NF-kappaB signaling pathway was evaluated with Western blot and luciferase
      reporter assay. miR-21 expression was determined using real-time PCR. miR-21
      inhibitor and miR-21 mimic were used to downregulate and upregulate miR-21
      expression, respectively. RESULTS: It was identified that celastrol was capable
      of inducing apoptosis of gastric cancer cells, which was mediated via inhibiting
      the activation of PI3K/Akt and NF-kappaB. A strong activator of Akt, IGF-1
      restored NF-kappaB activity in cells treated with celastrol. Celastrol could also
      significantly suppress miR-21 expression. Furthermore, miR-21 inhibitor could
      decrease phospho-Akt expression and NF-kappaB activity. Notably, upregulation of
      miR-21 expression can increase PI3K/Akt and NF-kappaB activity and decrease
      apoptosis of gastric cancer cells treated with celastrol, which could be reversed
      by PI3K inhibitor. CONCLUSIONS: Our data revealed that the effect of celastrol on
      apoptosis was due to miR-21 inhibiting the PI3K/Akt-dependent NF-kappaB pathway.

PMID- 24434353
TI  - Molecular mechanisms of congenital heart block.
AB  - Autoantibody-associated congenital heart block (CHB) is a passively acquired
      autoimmune condition associated with maternal anti-Ro/SSA antibodies and
      primarily affecting electric signal conduction at the atrioventricular node in
      the fetal heart. CHB occurs in 1-2% of anti-Ro/SSA antibody-positive pregancies
      and has a recurrence rate of 12-20% in a subsequent pregnancy. Despite the long
      recognized association between maternal anti-Ro/SSA autoantibodies and CHB, the
      molecular mechanisms underlying CHB pathogenesis are not fully understood, but
      several targets for the maternal autoantibodies in the fetal heart have been
      suggested. Recent studies also indicate that fetal susceptibility genes determine
      whether an autoantibody-exposed fetus will develop CHB or not, and begin to
      identify such genes. In this article, we review the different lines of
      investigation undertaken to elucidate the molecular pathways involved in CHB
      development and reflect on the hypotheses put forward to explain CHB pathogenesis
      as well as on the questions left unanswered and that should guide future studies.

PMID- 24434354
TI  - A synthetic mechano-growth factor E peptide promotes rat tenocyte migration by
      lessening cell stiffness and increasing F-actin formation via the FAK-ERK1/2
      signaling pathway.
AB  - Tendon injuries are common in sports and are frequent reasons for orthopedic
      consultations. The management of damaged tendons is one of the most challenging
      problems in orthopedics. Mechano-growth factor (MGF), a recently discovered
      growth repair factor, plays positive roles in tissue repair through the
      improvement of cell proliferation and migration and the protection of cells
      against injury-induced apoptosis. However, it remains unclear whether MGF has the
      potential to accelerate tendon repair. We used a scratch wound assay in this
      study to demonstrate that MGF-C25E (a synthetic mechano-growth factor E peptide)
      promotes the migration of rat tenocytes and that this promotion is accompanied by
      an elevation in the expression of the following signaling molecules: focal
      adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2).
      Inhibitors of the FAK and ERK1/2 pathways inhibited the MGF-C25E-induced tenocyte
      migration, indicating that MGF-C25E promotes tenocyte migration through the FAK
      ERK1/2 signaling pathway. The analysis of the mechanical properties showed that
      the Young's modulus of tenocytes was decreased through treatment of MGF-C25E, and
      an obvious formation of pseudopodia and F-actin was observed in MGF-C25E-treated
      tenocytes. The inhibition of the FAK or ERK1/2 signals restored the decrease in
      Young's modulus and inhibited the formation of pseudopodia and F-actin. Overall,
      our study demonstrated that MGF-C25E promotes rat tenocyte migration by lessening
      cell stiffness and increasing pseudopodia formation via the FAK-ERK1/2 signaling
      pathway. 

PMID- 24434355
TI  - Efficient programming of human eye conjunctiva-derived induced pluripotent stem
      (ECiPS) cells into definitive endoderm-like cells.
AB  - Due to pluripotency of induced pluripotent stem (iPS) cells, and the lack of
      immunological incompatibility and ethical issues, iPS cells have been considered
      as an invaluable cell source for future cell replacement therapy. This study was
      aimed first at establishment of novel iPS cells, ECiPS, which directly
      reprogrammed from human Eye Conjunctiva-derived Mesenchymal Stem Cells (EC-MSCs);
      second, comparing the inductive effects of Wnt3a/Activin A biomolecules to IDE1
      small molecule in derivation of definitive endoderm (DE) from the ECiPS cells. To
      that end, first, the EC-MSCs were transduced by SOKM-expressing lentiviruses and
      characterized for endogenous expression of embryonic markers Then the established
      ECiPS cells were induced to DE formation by Wnt3a/Activin A or IDE1.
      Quantification of GSC, Sox17 and Foxa2 expression, as DE-specific markers, in
      both mRNA and protein levels revealed that induction of ECiPS cells by either
      Wnt3a/Activin A or IDE1 could enhance the expression level of the genes; however
      the levels of increase were higher in Wnt3a/Activin A induced ECiPS-EBs than IDE1
      induced cells. Furthermore, the flow cytometry analyses showed no synergistic
      effect between Activin A and Wnt3a to derive DE-like cells from ECiPS cells. The
      comparative findings suggest that although both Wnt3a/Activin A signaling and
      IDE1 molecule could be used for differentiation of iPS into DE cells, the DE
      inducing effect of Wnt3a/Activin A was statistically higher than IDE1. 

PMID- 24434356
TI  - Activation-induced cytidine deaminase (AID) is localized to subnuclear domains
      enriched in splicing factors.
AB  - Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive
      immunity. AID initiates the antibody diversification processes in activated B
      cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent
      other genes are also targeted, which may lead to genome instability and B cell
      malignancy. Thus, it is crucial to understand its targeting and regulation
      mechanisms. AID is regulated at several levels including subcellular
      compartmentalization. However, the complex nuclear distribution and trafficking
      of AID has not been studied in detail previously. In this work, we examined the
      subnuclear localization of AID and its interaction partner CTNNBL1 and found that
      they associate with spliceosome-associated structures including Cajal bodies and
      nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by
      phosphorylation at Ser38, is present together with AID in nuclear speckles.
      Importantly, we demonstrate that AID physically associates with the major
      spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other
      essential splicing components, in addition to the transcription machinery. Based
      on our findings and the literature, we suggest a transcription-coupled splicing
      associated model for AID targeting and activation. 

PMID- 24434357
TI  - Emergency ultrasound of the chest.
AB  - Thoracic ultrasound is a noninvasive and portable diagnostic tool which is highly
      indicated for an initial workup of thoracic emergencies. The suspicion of a
      pneumothorax, pneumonia, pulmonary embolism or a lung contusion after trauma can
      be quickly assessed using ultrasound. Main advantages are its good availability
      and the steep learning curve. Another advantage of thoracic sonography is that
      this rapid, symptom-based examination has a high sensitivity and specificity.
      However, a disadvantage is that only pleura-affecting lesions or lesions visible
      through a sound window, e.g. an effusion or a subpleural consolidation, can be
      reached.

PMID- 24434359
TI  - Diagnosis and classification of psoriasis.
AB  - Psoriasis is a chronic inflammatory multi organ disease with well characterized
      pathology occurring in the skin and often the joints. Although the disease has
      many characteristic and even pathognomonic features, no established diagnostic
      criteria exist for cutaneous psoriasis and there is no unified classification for
      the clinical spectrum of the disease. Prior approaches that have been taken to
      classify psoriasis include age of onset, severity of the disease, and morphologic
      evaluation. The latter has yielded plaque, guttate, pustular, and erythrodermic
      as subtypes of psoriasis. Unlike other autoimmune diseases, histopathological
      examination and blood tests are generally not valuable tools in making the
      diagnosis of psoriasis. However, on occasion, dermatopathologic evaluation may be
      helpful in confirming the diagnosis of psoriasis. Thus, in most cases the
      diagnosis of psoriasis is dependent primarily on pattern recognition that is
      morphologic evaluation of skin lesions and joints. 

PMID- 24434358
TI  - Diagnosis and classification of autoimmune blistering diseases.
AB  - Blistering skin diseases are a group of autoimmune disorders that are
      characterized by autoantibodies against structural proteins of the epidermis or
      the dermal-epidermal junction and clinically by blisters and erosions on skin
      and/or mucous membranes. Since clinical criteria and histopathological
      characteristics are not sufficient for diagnosis, direct immunofluorescence
      microscopy of a biopsy specimen or serological tests are needed for exact
      diagnosis. The differentiation between the various disorders became more
      important since prognosis as well as different treatment options are nowadays
      available for the various diseases. Moreover, some bullous diseases may indicate
      the presence of an underlying malignancy. The detection of serum autoantibodies
      have been shown to correlate with disease activity and thus may be helpful in
      deciding treatment options for these patients. 

PMID- 24434360
TI  - Hashimoto thyroiditis: clinical and diagnostic criteria.
AB  - Hashimoto thyroiditis (HT), now considered the most common autoimmune disease,
      was described over a century ago as a pronounced lymphoid goiter affecting
      predominantly women. In addition to this classic form, several other clinico
      pathologic entities are now included under the term HT: fibrous variant, IgG4
      related variant, juvenile form, Hashitoxicosis, and painless thyroiditis
      (sporadic or post-partum). All forms are characterized pathologically by the
      infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the
      interstitium among the thyroid follicles, although specific features can be
      recognized in each variant. Thyroid cells undergo atrophy or transform into a
      bolder type of follicular cell rich in mitochondria called Hurthle cell. Most HT
      forms ultimately evolve into hypothyroidism, although at presentation patients
      can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the
      demonstration of circulating antibodies to thyroid antigens (mainly
      thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram
      in a patient with proper clinical features. The treatment remains symptomatic and
      based on the administration of synthetic thyroid hormones to correct the
      hypothyroidism as needed. Surgery is performed when the goiter is large enough to
      cause significant compression of the surrounding cervical structures, or when
      some areas of the thyroid gland mimic the features of a nodule whose cytology
      cannot be ascertained as benign. HT remains a complex and ever expanding disease
      of unknown pathogenesis that awaits prevention or novel forms of treatment. 

PMID- 24434361
TI  - Diagnosis and classification of autoimmune hypophysitis.
AB  - Autoimmmune hypophysitis (AH) is the consequence of an immune-mediated
      inflammation of the pituitary gland. The initial pituitary enlargement, secondary
      to infiltration and oedema, can evolve to remission, for spontaneous or
      pharmacological resolution of the inflammation, or evolve to progressive diffuse
      destruction with gland atrophy for fibrotic replacement, thus leading to various
      degrees of pituitary dysfunction. The autoimmune process against the pituitary
      gland is made evident by the appearance of circulating autoantibodies (APA),
      mainly detected by indirect immunofluorescence on cryostatic sections of human or
      primate pituitary. Among the target autoantigens recognized by APA are alpha
      enolase, gamma-enolase, the pituitary gland specific factors (PGSF) 1 and 2 and
      corticotroph-specific transcription factor (TPIT). However, the low diagnostic
      sensitivity and specificity of APA for AH strongly limit the clinical use of this
      marker. AH should be considered in the differential diagnosis of non-secreting
      space-occupying lesions of sella turcica, to avoid misdiagnosis that may lead to
      an aggressive surgery approach, since endocrine dysfunction and the compressive
      effect may be transient. 

PMID- 24434362
TI  - Diagnosis and classification of IgA nephropathy.
AB  - IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The
      diagnostic hallmark of IgAN is the predominance of IgA deposits in the glomerular
      mesangium. The natural history of IgAN is variable. Clinical features including
      heavy proteinuria, elevated serum creatinine level, hypertension at presentation,
      and advanced histologic findings can strongly predict the risk of progressive
      chronic kidney disease. This article reviews the evolving history of diagnostic
      criteria of IgAN and the controversial aspects of the Oxford Classification. To
      date, there is no disease-targeted treatment for IgAN. Advances in understanding
      of the pathogenesis may help with earlier diagnosis and better monitoring of the
      treatment response and clinical course, and in the development of targeted
      therapy in the future. 

PMID- 24434363
TI  - Guillain Barre syndrome and other immune mediated neuropathies: diagnosis and
      classification.
AB  - Immune mediated neuropathies are uncommon but important to diagnose because they
      are potentially treatable. This chapter summarizes the clinical approach to
      diagnosis of Guillain Barre syndrome (GBS), chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP), and related neuropathies which are thought to be
      caused by direct autoimmune attack on peripheral nerves. 

PMID- 24434364
TI  - Cervical spine instability following axial compression injury: a biomechanical
      study.
AB  - BACKGROUND: Axial compression injuries of the cervical spine occur during contact
      sports, automobile collisions, and falls. The objective of this study was to use
      flexibility tests to determine biomechanical instability of the cervical spine
      due to simulated axial compression injuries. HYPOTHESIS: We hypothesized that the
      axial compression injuries cause severe biomechanical instability throughout the
      cervical spine. MATERIALS AND METHODS: The injuries were simulated using 2.4m/s
      head-first impacts of a cadaveric cervical spine model (n=10) mounted
      horizontally to a torso-equivalent mass on a sled and carrying a surrogate head
      in protruded posture. Intact and post-impact flexibility tests were performed up
      to 1.5, 3, and 1.5 Nm in flexion-extension, axial torque, and lateral bending,
      respectively. Instability parameters of range of motion (RoM) and neutral zone
      (NZ) were determined for injured spinal levels and statistically compared
      (P<0.05) between intact and post-impact. RESULTS: The sagittal instability
      parameters indicated extension-compression injuries at the upper and middle
      cervical spine and flexion-compression injuries at the lower cervical spine.
      Increases in extension RoM were 14.9 degrees  at the upper cervical spine and
      24.9 degrees  (P<0.05) at the middle cervical spine and in flexion RoM at C7/T1
      were 25.6 degrees . RoM and NZ increases in axial rotation and lateral bending
      were nearly symmetric among left and right. DISCUSSION: Multidirectional
      instability of the upper cervical spine caused by atlas and dens fractures was
      evidenced by increases between 36% and 53% in RoM and NZ due to the impacts. The
      sagittal RoM of injured spinal levels of the middle and lower cervical spine
      exceeded a proposed threshold for clinical instability by between 67% and 114%.
      The instability documented throughout the cervical spine was consistent with
      clinical observations of cord injuries and paralysis in patients. LEVEL OF
      EVIDENCE: Level IV, controlled laboratory investigation.

PMID- 24434365
TI  - Treatment of recent trochanteric fracture in adults.
AB  - Recent trochanteric fracture is frequent in adults, and mainly affects elderly
      patients who risk loss of independence. Treatment is surgical, of various sorts.
      Open reduction internal fixation (ORIF) with intra- or extra-medullary implants
      is the most frequent attitude in these fractures, which usually heal easily. In
      elderly patients, arthroplasty is an alternative of choice for some authors.
      These different treatment modalities are presented, focusing on technical
      details. Possible technical difficulties and the means of dealing with them are
      considered. Published results help in choosing the treatment most suitable for a
      particular type of fracture in a particular patient. 

PMID- 24434366
TI  - Surgical management of recurrent dislocation after total hip arthroplasty.
AB  - Dislocation is a major complication of total hip arthroplasty (THA), whose
      frequency has been unaffected by improvements in surgical techniques and
      implants. The dislocation rate depends on multiple factors related to the
      patient, hip disease, and surgical procedure and is therefore also dependent on
      the surgeon. The many published studies on THA dislocation, its causes, and its
      treatment have produced conflicting results. The objective of this work is to
      review the management of THA dislocation, which is a severe event for both the
      patient and the surgeon. This lecture starts with a brief review of data on THA
      dislocation rates and the many factors that influence them. Emphasis is then put
      on the evaluation for a cause and, more specifically, on the challenges raised by
      detecting suboptimal cup position. Next, reported techniques for treating THA
      dislocation and the outcomes of each are discussed. Finally, a management
      strategy for patients selected for revision surgery is suggested. 

PMID- 24434367
TI  - Computational identification and characterization of conserved miRNAs and their
      target genes in garlic (Allium sativum L.) expressed sequence tags.
AB  - The endogenous small non-coding functional microRNAs (miRNAs) are short in size,
      range from ~21 to 24 nucleotides in length, play a pivotal role in gene
      expression in plants and animals by silencing genes either by destructing or
      blocking of translation of homologous mRNA. Although various high-throughput,
      time consuming and expensive techniques like forward genetics and direct cloning
      are employed to detect miRNAs in plants but comparative genomics complemented
      with novel bioinformatic tools pave the way for efficient and cost-effective
      identification of miRNAs through homologous sequence search with previously known
      miRNAs. In this study, an attempt was made to identify and characterize conserved
      miRNAs in garlic expressed sequence tags (ESTs) through computational means. For
      identification of novel miRNAs in garlic, a total 3227 known mature miRNAs of
      plant kingdom Viridiplantae were searched for homology against 21,637 EST
      sequences resulting in identification of 6 potential miRNA candidates belonging
      to 6 different miRNA families. The psRNATarget server predicted 33 potential
      target genes and their probable functions for the six identified miRNA families
      in garlic. Most of the garlic miRNA target genes seem to encode transcription
      factors as well as genes involved in stress response, metabolism, plant growth
      and development. The results from the present study will shed more light on the
      understanding of molecular mechanisms of miRNA in garlic which may aid in the
      development of novel and precise techniques to understand some post
      transcriptional gene silencing mechanism in response to stress tolerance. 

PMID- 24434368
TI  - Incidence, complexity and diversity of simple sequence repeats across potexvirus
      genomes.
AB  - An in-silico analysis of simple sequence repeats (SSRs) in genomes of 32 species
      of potexviruses was performed wherein a total of 691 SSRs and 33 cSSRs were
      observed. Though SSRs were present in all the studied genomes their incident
      frequency ranged from 11 to 30 per genome. Further, 10 potexvirus genomes
      possessed no cSSRs when extracted at a dMAX of 10 and wherein present, the
      highest frequency was 3. SSR and cSSR incidence, relative density and relative
      abundance were non-significantly correlated with genome size and GC content
      suggesting an ongoing evolutionary and adaptive phase of the virus species. SSRs
      present primarily ranged from mono- to tri-nucleotide repeat motifs with a
      greatly skewed distribution across the coding and non-coding regions. Present
      work is an effort for the undergoing compilation and analysis of incidence,
      distribution and variation of the viral repeat sequences to understand their
      evolutionary and functional relevance. 

PMID- 24434369
TI  - Isolation and expression analysis of proline metabolism-related genes in
      Chrysanthemum lavandulifolium.
AB  - Proline plays a significant role in plant resistance to abiotic stresses, and its
      level is determined by a combination of synthesis, catabolism and transport. The
      primary proteins involved are Delta(1)-pyrroline-5-carboxylate synthetase (P5CS),
      proline dehydrogenase (PDH) and proline transporter (ProT). To utilise proline
      metabolism to improve the stress resistance of Chrysanthemum*morifolium, we
      isolated two P5CS-homologous genes (ClP5CS1 and ClP5CS2), one PDH gene (ClPDH)
      and four ProT-homologous genes (ClProT1-4) (GenBANK accession numbers: KF743136
      KF743142) from Chrysanthemum lavandulifolium, which is closely related to
      chrysanthemums and exhibits strong resistance to stresses. Expression analysis of
      these genes in different organs and under various stresses indicated that ClP5CSs
      showed substantial constitutive expression, while ClPDH was only strongly
      expressed in the capitulum and was inhibited under most stresses. The expression
      patterns of four ClProT genes presented characteristics of organ specificity and
      disparity under stresses. Above all, the expression of ClProT2 was restricted to
      above-ground organs, especially strong in the capitulum and could be obviously
      induced by various stress conditions. Promoters of ClPDH and ClProTs contained
      many cis-acting regulatory elements involved in stress responses and plant growth
      and development. High levels of free proline were found in flower buds, the
      capitulum under the non-stress condition and later periods of stress conditions
      except cold treatment. Interestingly, organ specificity and disparity also exist
      in the level of free proline under different stress conditions. Our study
      indicates that ClProTs play significant roles in proline accumulation and stress
      responses, and that ClProT2 could be used to genetically modify the stress
      resistance of chrysanthemums. In addition, proline metabolism might be closely
      related to plant flowering and floral development.

PMID- 24434370
TI  - Darunavir minimum plasma concentration and ritonavir-boosted darunavir
      monotherapy outcome in HIV-infected patients.
AB  - BACKGROUND: This study aimed to evaluate whether low darunavir (DRV) minimum
      plasma concentration (Cmin) values contribute to virological outcomes during
      DRV/ritonavir monotherapy (mtDRV/rtv). METHODS: This was a prospective
      observational single-arm 96-week efficacy study in virologically suppressed
      subjects on triple therapy switched to mtDRV/rtv (800/100 mg every 24 h).
      Previous virological failures (VF) on protease-inhibitor-based regimens were
      allowed if the historical resistance tests showed no major resistance mutation to
      DRV/rtv. VF was defined as two consecutive HIV RNA measurements of >200
      copies/ml. Efficacy was analysed by per-protocol and by intention-to-treat
      analyses. Plasma DRV Cmin values were measured by LC-MS/MS. RESULTS: A total of
      150 subjects were included. At week 96, the efficacy rate on treatment was 83.6%
      (95% CI 77.2%, 90.0%) by per-protocol analysis and 67.6% (95% CI 60.0%, 75.2%) by
      intention-to-treat. In the whole cohort the median (IQR) DRV Cmin was
      significantly higher during the periods of undetectable than of detectable
      viraemia (1.82 ug/ml [1.47-2.46] versus 1.56 ug/ml [0.93-2.32]; P=0.006) as well
      as in the subjects with blips and VF. However, a cutoff point sufficiently
      sensitive and specific could not be found. CONCLUSIONS: The DRV Cmin values are
      related to viral control during mtDRV/rtv, but therapeutic drug monitoring cannot
      be recommended routinely as a precise cutoff point is unknown. Adherence is a key
      success factor on this regimen.

PMID- 24434372
TI  - Fluticasone furoate is more effective than mometasone furoate in restoring
      tobacco smoke inhibited SOCS-3 expression in airway epithelial cells.
AB  - Fluticasone furoate (FF) and mometasone furoate (MF) are potent glucocorticoids
      recommended for the treatment of allergic rhinitis and other inflammatory
      diseases. However, whether these drugs render any anti-inflammatory effects in
      Chronic Obstructive Pulmonary Disease (COPD) is unclear. Emerging data on
      suppressors of cytokine signaling-3 (SOCS-3) activation in the lungs during
      inflammation suggests that SOCS3 can be potential targets for regulating
      pulmonary inflammatory responses in COPD. In this study, we compared the effect
      of FF with MF on SOCS-3 expression in tobacco smoke (TS) exposed BAEpCs in vitro
      and in a mouse model of COPD in vivo. BAEpCs were exposed to TS or room air and
      later were treated with either FF (1nmol-100nmol) or MF (10-500nmol) inhibitors
      in the presence and absence of Jak1 and Stat-3 inhibitors. C57BL/6 mice were
      exposed to TS for 6 months, and treated with either FF, MF for 2 and 4 weeks. FF
      induced 7 fold increases in SOCS-3 expression in BAEpCs whereas MF induced a
      three fold increase when compared to control. Jak1 and Stat-3 inhibitors
      significantly inhibited the FF and MF induced SOCS-3 expression in BAEpCs. In
      addition, FF and MF restored TS inhibited SOCS-3 expression in the airway
      epithelium of COPD mice. FF and MF treatments significantly reduced leukocyte
      infiltration in airways and inhibited lung inflammation. Our study elucidates a
      novel mechanism for the anti-inflammatory action of FF in COPD. The superior
      efficacy of FF may be in part due to the increased expression of SOCS-3 in
      BAEpCs. 

PMID- 24434371
TI  - Echinacea purpurea (L.) Moench modulates human T-cell cytokine response.
AB  - The study objective was to evaluate the composition of a neutral and weakly
      acidic water-soluble extract from Echinacea purpurea (L.) Moench (EchNWA)
      previously shown to modify murine influenza infection, and to assess
      immunomodulatory effects on human T-cells. EchNWA extract from fresh aerial parts
      was extracted with water, ethanolic precipitation, and size-exclusion
      chromatography. The chemical profile of EchNWA was characterized by
      chromatography (size-exclusion, HPLC, GC-MS), and small molecule fingerprint
      analysis performed by HPLC-PDA. Jurkat T-cells at high and low cell density were
      pretreated or not with doses of EchNWA, followed by activation with phorbol 12
      myristate 13-acetate plus ionomycin (PMA+I). Interleukin-2 (IL-2) and interferon
      gamma (IFNg) cytokine secretions were measured by multi-cytokine luminex
      technology. Results showed that EchNWA contains 80% polysaccharides,
      predominantly a 10kDa entity; phenolic compounds, cynarin, cichoric and caftaric
      acids, but no detectable alkylamides. Cytokine production required stimulation
      and was lower after PMA+I activation in high-density compared to low-density
      conditions. EchNWA mediated a strong dose-dependent enhancement of high-density T
      cell production of IL-2 and IFNg response to PMA+I. EchNWA alone did not
      stimulate T-cells. EchNWA enhanced mean fluorescence intensity of IL-2 in Jurkat
      T-cells activated by PMA+1 or ionomycin alone. Conversely EchNWA mediated modest
      but significant suppression of IFNg response and reduced the percentage of CD25+
      T-cells under low-density conditions. Conclusions are that EchNWA
      polysaccharides, but not phenolic compounds have dose-related adjuvant effects on
      human T-cell cytokine responses characterized by enhancing and suppressive
      effects that are regulated by T-cell density. 

PMID- 24434373
TI  - Comparison of the carbohydrate preference of SIGNR1 as a phagocytic receptor with
      the preference as an adhesion molecule.
AB  - C-type lectin receptors expressed on cell surfaces of antigen-presenting cells
      can serve as not only cell adhesion molecules but also as phagocytic receptors,
      and therefore, are potentially useful for antigen targeting for vaccination. In
      the present study, we compared the carbohydrate preference of the C-type lectin
      SIGNR1 as a cell adhesion molecule with that of SIGNR1 as a phagocytic receptor,
      using a series of neoglycolipids (NGLs) and the mouse macrophage-like cells
      stably expressing SIGNR1. When SIGNR1-mediated cell adhesion was assessed based
      on the binding of the cells to NGL-coated solid phases, the order of degree of
      cell adhesion was Le(b)-~Le(a)-~Le(x)->=Man5->Man3->=alpha1-3Man2->alpha1-6Man2
      DPPE. By contrast, when SIGNR1-mediated phagocytosis was assessed based on the
      uptake of NGL-coated liposomes, the order of phagocytosis of the liposomes by the
      cells was Le(a)-~Man3->Man5-~alpha1-3Man2->Le(x)->Le(b)->alpha1-6Man2-DPPE.
      Collectively, SIGNR1 mediates cell adhesion to Lewis blood group antigen
      containing NGL-coated solid phases more preferably than those coated with
      terminal mannose-containing NGLs, but mediates the phagocytosis of the Man3-DPPE-
      and Le(a)-DPPE-coated liposomes most preferably among the tested NGLs. Thus, the
      subtle carbohydrate preference of SIGNR1 on the cell surface is altered depending
      on the function, and the preferable carbohydrate for phagocytosis elucidated
      using NGL-coated liposomes might be used as the appropriate targeting signals for
      antigen delivery. 

PMID- 24434374
TI  - The forgotten diagnostic caveats in Takotsubo cardiomyopathy.

PMID- 24434375
TI  - Hepatitis C virus infection in dialysis patients.
AB  - Despite the introduction of strict hygienic precautions preventing infection
      spread of hepatitis C virus (HCV) in dialysis settings, this infection is still
      prevalent among dialysis patients due to procedures making the patients
      vulnerable to infection through blood contamination. Treatment of HCV infection
      in dialysis patients is also less successful than that in the non-uremic
      population due to contraindication of using ribavirin, a main drug, in the
      infected patients. In this review article we aim to investigate the feasibility
      of the current antiviral therapies in dialysis patients infected with HCV
      infection. 

PMID- 24434376
TI  - Anti-thymocyte globulin versus basiliximab induction in renal transplant
      recipients: Long-term outcome.
AB  - Although basiliximab and rabbit anti-thymocyte globulin (ATG) are effective in
      delaying and reducing the incidence of acute rejection (AR) thus improving short
      term graft survival, their impact on long-term graft survival has not been well
      established in renal transplant recipients. To evaluate the long-term efficacy
      after induction therapy with ATG/basiliximab in renal transplant recipients, we
      studied retrospectively 86 renal transplant recipients of living donor renal
      transplantation from 2003 to 2006; of them, 42 patients received induction with
      ATG three doses of 50 mg, 25 mg, 25 mg/day on 0, 1 and 2 post-operative days
      (POD) and 44 age-matched patients received induction with basiliximab (20 mg/day
      on 0 and 4 PODs). All the patients received tacrolimus, mycophenolate mofetil and
      corticosteroids as maintenance immunosuppressive therapy. Demographic
      characteristics were similar between both groups. Patient survival at 5 years was
      90.5% in the ATG group and 84.1% in the basiliximab group, while graft survival
      was 83.4% and 77.3%, respectively. The incidence of acute rejection was 14.2% and
      18.1% in the ATG and the basiliximab groups, respectively. The estimated mean
      glomerular filtration rates at 5 years post-transplantation was 52.1 mL/min and
      49.1 mL/min and the mean serum creatinine levels were 1.55 +/- 0.37 and 1.66 +/-
      0.51 mg/dL in the ATG and basiliximab groups, respectively. A low incidence of
      tuberculosis and cytomegalovirus (CMV) was observed in the ATG group. There were
      no significant differences between the two groups, and both induction regimens
      assured a safe and effective treatment and were associated with similar excellent
      long-term patient and graft survival. 

PMID- 24434377
TI  - The seroprevalence of Parvovirus B19 among kidney transplant recipients: a single
      center study.
AB  - Parvovirus B19 is a DNA virus that is responsible for causing several diseases in
      humans. Parvovirus B19-induced persistent anemia is one of its manifestations
      that is relatively common in transplant recipients. This study was aimed to
      investigate the seroprevalence of parvovirus B19 among kidney transplant
      recipients. Ninety-one transplant recipients were selected randomly and were
      investigated for several variables including age, gender, educational status,
      history of hemodialysis (HD), history of blood transfusion and immunosuppressive
      therapy. Two milliliters of blood samples were collected via venipuncture and
      evaluated for anti-Parvovirus B19 IgG antibody using enzyme-linked immunosorbent
      assay. All recipients were anemic, with 72.5% of them suffering from severe
      anemia (Hb <= 11 in men and <= 10 in women). Sixty-three patients (69.2%) were
      seropositive for Parvovirus B19. There was no significant difference in age, sex,
      educational status, history of blood transfusion, history of HD and
      immunosuppressive therapy between seropositive and seronegative groups. The
      seroprevalence of Parvovirus B19 was relatively high in kidney transplant
      recipients in Urmia, Iran. Our study failed to find a correlation between the
      severity of anemia and the seropositivity of Parvovirus B19. 

PMID- 24434378
TI  - Hypertension in post-renal transplant patients: pilot study.
AB  - Post-transplant hypertension is a major risk factor for graft loss and patient
      survival; therefore, hypertension following renal transplantation must be treated
      strictly. There seems to be a strong association between hypertension, total body
      water (TBW) and dry weight. In this study, we report the relationship of body
      water and body composition with hypertension in post-renal transplant patients.
      Forty-five post-transplant patients were enrolled in the study. Blood pressure
      (BP) was labeled as controlled if BP was 120/80 mm Hg and not under good control
      if BP was above 120/80 mm Hg. Based on the number of antihypertensive medications
      a patient was taking, patients were divided into two groups: Group 1 patients on
      one antihypertensive drug and Group 2 patients on more than one antihypertensive
      drug. Nutritional status of the patients was assessed. Body composition (water
      compartments, body fat and lean mass) was assessed using bioelectrical impedance
      analysis (BIA). Patient data were compared with 30 healthy volunteers. In
      patients, systolic BP was associated with TBW (P = 0.016), extracellular water
      (ECW Lt; r = 0.99), ECW% (r = 0.78) and diastolic BP with TBW% (P = 0.003), dry
      weight (r = 0.76) ECW% (r = 0.95) and percent intracellular water (ICW%) (r =
      0.79). Compared with controls, ECW and ECW% was higher in patients, and the ICW%
      was less in patients. There was significant difference in the actual weight of
      the patients and BIA-derived dry weight, although patients were clinically not
      edematous. The study showed a significant increase in diastolic BP with increase
      in dry weight. Significant difference in TBW was observed when the patients were
      grouped on the basis of the antihypertensive medication a patient was taking (one
      antihypertensive drug versus more than one antihypertensive drug). This study
      also showed an association between hypertension and overhydration. BIA may be a
      useful tool for the clinical assessment of overhydration in non-edematous
      patients. 

PMID- 24434379
TI  - CD20 antigen expression by lymphoma cells in lung allograft recipients is
      associated with higher remission rate and superior survival: a study on heart and
      lung transplant recipients.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are one of the fatal
      complications of transplantation, and there is scarcity of data on the relevance
      of antigen expression by tumor cells in PTLD. In the current study, we aimed to
      investigate the potential effects of CD20 antigen expression by PTLD lesions
      developing in heart/lung transplant recipients. A comprehensive search was
      performed for reports indicating CD20 antigen tests in PTLD lesions developing in
      heart and/or lung transplant recipients. For data accumulation, we developed a
      standard questionnaire and data of patients presented in different published
      reports were entered into it. Finally, data from 26 previously published reports
      from different centers around the world were included in the analysis. CD20
      positive PTLD lesions are significantly more likely to be of the B cell type (P =
      0.006). PTLD in patients with a CD20-positive test represented relevantly shorter
      time from transplantation to PTLD, although it did not reach a significance level
      (P = 0.08). At the last follow-up, 53% patients were dead. Survival analysis
      showed no prognosis difference regarding CD20 test. When data were reanalyzed
      separately for heart and lung transplant recipients, lung recipients developing
      PTLD with a CD20-positive test were significantly more likely to represent
      remission episodes (P = 0.03), and also represented a significantly better
      outcome than CD20-negative PTLD patients (P = 0.04). CD20-positive PTLD lesions
      in heart/lung recipients are more likely of the B cell type and develop PTLD
      lesions earlier than their CD20-negative counterparts. Lung recipients developing
      CD20-positive PTLD lesions represented higher remission rates and better outcome.
      Further studies with prospective follow-up of patients are needed for confirming
      our findings. 

PMID- 24434380
TI  - Mean bone mineral density and frequency of occurrence of osteopenia and
      osteoporosis in patients on hemodialysis: a single-center study.
AB  - Chronic renal disease changes both quality and quantity of bone through multi
      factorial influences on bone metabolism, leading to osteopenia, osteoporosis and
      increased risk of fracture. The objectives of our present cross-sectional study
      were to determine the mean bone mineral density (BMD) and frequency of occurrence
      of osteoporosis and osteopenia in Saudi patients on hemodialysis (HD) for longer
      than 1 year. Forty-two male and 78 female patients with age between 20 and 50
      years were enrolled in this study. The BMD of the lumbar vertebral spine (LV) and
      the neck of femur (FN) were measured in all patients. Data were analyzed using
      SPSS version 17.0 software and the level of significance was considered as P
      <0.05. The mean BMD in the LV (L2-L4) was 1.155 +/- 0.026 g/cm 2 in male and
      1.050 +/- 0.025 g/cm 2 in female patients (P = 0.016). The mean BMD in the FN was
      1.010 +/- 0.023 g/cm 2 in male and 0.784 +/- 0.020 g/cm 2 in female patients (P =
      0.00). Based on the World Health Organization criteria, 73.8% of the male and
      44.9% of the female patients in our study had normal BMD (P = 0.002); 16.7% male
      and 28.2% female patients had osteopenia (P = 0.14), while 9.5% male and 26.9%
      female patients had osteoporosis (P = 0.01). This study showed a marked decrease
      in mean BMD in the cortical bone (FN) compared with trabecular bone (LV) (P =
      0.00) as well as in female patients on HD compared with male patients (P = 0.016
      for LV and P = 0.00 for FN). 

PMID- 24434381
TI  - The value of serum FGF-23 as a cardiovascular marker in HD patients.
AB  - Fibroblast growth factor 23 (FGF-23) is a recently discovered regulator of
      phosphate and mineral metabolism and has been associated with both progression of
      CKD and mortality in dialysis patients. To evaluate the association between serum
      FGF-23 levels and echocardiographic measurements in long-term HD (HD) patients
      without cardiac symptoms, we studied 90 consecutive patients treated in a single
      HD center (51 males, 39 females; mean age 41.5 +/- 14.2 years, mean HD duration
      71.2 +/- 14.2 months). Comprehensive echocardiography was performed after HD and
      blood samples were obtained before HD. The serum FGF-23 level in dialysis
      patients was 95.7 +/- 88.4 pg/mL. In univariate analysis, serum calcium levels (r
      = 0.33, P <0.05), serum creatinine (r = 0.34, P <0.05), serum albumin (r = 0.35,
      P <0.05) and left ventricular mass index (LVMI) (r = 0.33, P <0.001) were
      correlated weakly with the FGF-23 levels. Neither s. phosphorus nor calcium x
      phosphorus product correlated with FGF-23. In univariate regression analysis,
      only LVMI [beta = 0.42, P <0.05, confidence interval (CI) 0.3-4.3], serum calcium
      (beta= 0.87, P <0.001, CI 0.8-7.3), serum albumin (beta= 0.87, P < 0.001, CI 0.8
      7.3) and serum creatinine (beta= 0.67, P <0.05, CI 0.5-6.5) significantly
      correlated with FGF-23. FGF-23 was identified as a factor that is weakly
      associated with LVMI. Thus, FGF-23 alone may not be a parameter that can be used
      for evaluation of the cardiac status in HD patients.

PMID- 24434382
TI  - Expression comparison of azithromycin and clarithromycin in triple-therapy
      regimens for eradication of Helicobacter pylori in hemodialysis patients.
AB  - To compare a triple-therapy regimen based on change of antibiotic (azithromycin
      and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis
      (HD) patients, we studied in a prospective, randomized, double-blinded clinical
      trial 39 patients who had dyspepsia and showed two positive results from the
      diagnostic tests of H. pylori infection including anti-H. pylori serology and
      stool antigen (HpSAg) and urease breath test (UBT). The patients were divided
      into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and
      clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg,
      amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and
      compliance with triple therapy were reviewed at one visit per week. Both groups
      were prescribed their medications for 14 days. Of the 39 patients, only 37
      patients completed the treatment schedule (20 men and 19 women, with the mean
      being 59 years). Two patients died due to myocardial infarction before the start
      of treatment and were out of the study. The eradication rate of H. pylori,
      evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P
      value = 1.0). The results of our study showed no significant difference of
      azitromycin versus claritromycin in the eradication of H. pylori infection in HD
      patients. 

PMID- 24434383
TI  - Carotid artery stenosis in patients with chronic kidney disease undergoing
      dialysis: epidemiological aspects, main risk factors and appropriate diagnostic
      criteria.
AB  - Knowledge of the epidemiology and risk profile of peripheral vascular disease
      among patients with chronic kidney disease (CKD) has a potential role for
      determining its outcome. This study assessed the epidemiological aspects and risk
      factors of carotid artery stenosis (CAS), assessed by clinical ankle brachial
      index (ABI), in patients on dialysis. This study was performed on 84 patients
      with CKD undergoing hemodialysis (HD; n = 65) or peritoneal dialysis (PD; n =
      19). The ABI was measured using a concurrent oscillometric method and Color
      Doppler sonography. An ABI value >0.9 was defined as normal. Severity of the
      stenosis was determined using B-Mode sonography. Overall, CAS was seen in 51.2%
      of the study patients. No significant difference was found in the overall
      prevalence of CAS between the HD and PD groups (50.8% vs. 52.6%, P = 0.552). The
      mean ABI in the HD and PD groups was 1.13 and 1.06, respectively. Among patient
      characteristics, advanced age was found to be a predictor of CAS in the study
      patients. Gender, type of dialysis or underlying risk factors could not predict
      CAS. ABI measurement was an acceptable predictor of CAS, with a receiver operator
      characteristic of 0.645. The optimal cut-off for ABI for predicting CAS was
      identified at 1.0; this yielded a sensitivity of 70.8% and a specificity of 63.6%
      for the test. In conclusion, a notable number of patients undergoing dialysis for
      CKD had CAS. The main predictive factor was advanced age. ABI measurement seems
      to be an acceptable tool to diagnose CAS. 

PMID- 24434384
TI  - The effect of treatment with N-acetylcysteine on the serum levels of C-reactive
      protein and interleukin-6 in patients on hemodialysis.
AB  - Patients with end-stage renal disease (ESRD) are at an increased risk of
      cardiovascular disease due to many factors including inflammation and oxidative
      stress. N-acetylcysteine (NAC) is a thiol-containing anti-oxidant with anti
      inflammatory properties. We aimed to assess the effect of three months treatment
      with oral NAC on the plasma levels of inflammatory mediators like interleukin-6
      (IL-6) and C-reactive protein (hs-CRP) in patients on hemodialysis (HD). Twenty
      four patients (nine males and 15 females) on maintenance HD were recruited in the
      study. Their mean age was 55.3 years. All the patients received oral NAC (600 mg
      twice a day) for a period of three months. The serum levels of biomedical
      parameters and IL-6 and hs-CRP were measured at baseline and three months after
      initiation of treatment. A significant decrease in serum levels of hs-CRP (22.4
      vs. 5.2), IL-6 (8.1 vs. 3.6), parathyroid hormone (iPTH) (257.2 vs. 158.8),
      ferritin (632.0 vs. 515.1) and erythrocyte sedimentation rate (ESR) (54.2 vs.
      38.3) was observed following NAC treatment. Female subjects presented with a
      significantly higher change in serum levels of hs-CRP compared with males (23 vs.
      5.4). In three subjects who were less than 40 years old, the hs-CRP and IL-6
      levels showed an increase following NAC treatment. Our study found that short
      term oral NAC treatment might result in the reduction of IL-6 and hs-CRP in
      patients who are on regular HD. This suggests that patients with ESRD may benefit
      from the anti-inflammatory effects of NAC.

PMID- 24434385
TI  - Evaluation of the effect of pentoxifylline on erythropoietin-resistant anemia in
      hemodialysis patients.
AB  - Use of recombinant human erythropoietin (rh-Epo) improves hemoglobin (Hgb) in 90
      95% of the cases of anemia of chronic kidney disease (CKD). However, it is known
      that pro-inflammatory cytokines such as interferon-gamma (IFN-gamma), tumor
      necrosis factor-alfa (TNF-alpha) and interleukin-1 (IL-1) suppress
      erythropoiesis, resulting in inadequate response to rh-Epo. Pentoxifylline has
      been shown to have modulatory effects on the immune system. This prospective
      study to evaluate the effect of pentoxyphylline on erythropoeisis was performed
      on 15 (eight males, seven females) clinically stable patients who had been on
      hemodialysis for at least six months with anemia (Hgb of <10.7 g/dL) unresponsive
      to rh-Epo despite high doses. They were treated with 400 mg pentoxifylline
      tablets once daily for 12 weeks. Hgb increased after one and two months of drug
      administration, but significant changes were observed in eight (53%) patients
      after three months (P <0.05). Our study illustrates a probable new use for an old
      medicine. Three months treatment with pentoxifylline was seen to increase Hgb
      significantly in rh-Epo-resistant patients. More prospective studies with a
      larger sample size are needed to determine the inhibitory role of cytokines on
      hematopoiesis and exploring new drugs or new drug indications to overcome anemia
      in advanced renal failure.

PMID- 24434386
TI  - Expression of CD44 and P53 in renal cell carcinoma: association with tumor
      subtypes.
AB  - Renal cell carcinoma (RCC) is a common malignancy of the kidney and accurate
      prediction of prognosis is valuable for the design of adjuvant therapy and
      counseling and effective scheduling of follow-up visits. Molecular genetic
      investigations of CD44 and P53 in RCC may be helpful in this regard. We studied
      the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens
      of 64 RCC patients (37 male/27 female) who underwent surgery from 2003 to 2008 by
      immunohistochemistry and analyzed the correlation of P53 and CD44 expression in
      RCC and outcome. Thirteen of 64 (20.3%) specimens were P53 positive, 30/64
      (46.9%) were CD44 positive and five tumors with positive P53 expressed CD44
      protein (P = 0.5). A statistically significant correlation was not found between
      CD44 and P53 expression (P = 0.5) and age (P = 0.07), sex (P= 0.3), tumor size (P
      = 0.7), grade (P = 0.23), vascular invasion (P = 1.00) and ureteral invasion (P =
      1.00). Furthermore, a significant correlation was not found between P53
      expression with age (P = 0.3), sex (P = 0.7), tumor size (P = 0.7), grade (P =
      0.1), vascular invasion (P = 1.00) and ureteral invasion (P = 1.00). According to
      our findings, only P53 expression is generally accompanied by non-conventional
      subtype tumor.

PMID- 24434387
TI  - Urinary tract infections in pregnancy: evaluation of diagnostic framework.
AB  - This study was performed with the objective to examine the diagnostic framework
      for urinary tract infection (UTI) in pregnancy and physician response to the
      clinical diagnosis and to correlate responses to the results of urine culture and
      sensitivity. Over a 6-month period, 81 consecutive patients attending the labor
      ward admission of a district general hospital with the diagnosis of UTI during
      pregnancy were analyzed. Relevant information on symptom complex, result of
      dipstick urinalysis and culture and sensitivity were recorded. Data were analyzed
      using descriptive statistics. Of the 78 patients analyzed, 79% had increased
      urinary frequency, 73.1% had suprapubic pains and 53.1% had dysuria. All the
      patients had urinalysis with dipsticks, 41 (52.6%) were positive for nitrites and
      64 (82.1%) were positive for leukocyte esterase. All 78 patients had urine
      culture and sensitivity, 21 (26.8%) of who were positive, and coliforms were the
      most commonly isolated pathogens. The sensitivity for nitrite was 80.9%,
      specificity 57.9% and positive predictive value 41.4%. The corresponding figures
      for leukocyte esterase were sensitivity 100%, specificity 24.6% and positive
      predictive value 32.8%. Sixty-six (84.6%) patients had treatment started on the
      basis of the clinical diagnosis, mostly with co-amoxyclavullinic acid or
      amoxicillin alone. A high resistance rate to these empirically chosen antibiotics
      was seen in the sensitivity pattern of isolated pathogens. Current clinical
      diagnostic algorithms for the diagnosis of UTI when applied in the context of
      pregnancy have low specificity and positive predictive values; yet, empirical
      antibiotics are frequently employed on this basis. These are often not in keeping
      with the sensitivity pattern of isolated organisms. There is need for a
      continuing research for more specific bedside tests.

PMID- 24434388
TI  - Monitoring the microbiological quality of dialysate and treated water.
AB  - During hemodialysis and related therapies, removal of waste products from the
      blood is made possible across a semi-permeable membrane. The microbiological
      quality of treated water (TW) and dialysate influences a number of dialysis
      related complications. This article is a review of the microbiological features
      of TW and dialysate fluid over a six-year period (February 2007 to December 2012)
      in the Dialysis Unit, 1 st Medico-Surgical Hospital, Agadir, Morocco.
      Installation of a water treatment unit has been followed by a protocol to check
      its quality periodically. Results of microbiological monitoring (microorganisms
      and endotoxins) were collected over a six-year period. Fifty-four samples of TW
      and 12 samples of dialysate fluid were analyzed for colony forming units (CFU)
      and endotoxin during this period. All dialysate samples were negative, while in
      the TW, 9.2% of the samples yielded >100/mL CFU and 16.7% yielded >0.06 EU/mL of
      endotoxins. These abnormal results happened especially during the first two first
      years. More frequent disinfection of the distribution loop was the corrective
      measure. To obtain high-quality water for hemodialysis, the appropriate system
      must be continuously monitored in order to get high microbiological quality of TW
      and dialysate fluid.

PMID- 24434389
TI  - Renovascular hypertension: a report of 21 cases.
AB  - Renovascular hypertension (RVH) is among the most common forms of secondary
      hypertension. We studied 21 patients (eight male and 13 female) with RVH who were
      encountered during a period of 16 years. The average age of the patients was
      34.75 years. Trans-renal Doppler ultrasound confirmed the diagnosis of
      renovascular stenosis (RAS) as the cause of RVH in 95% of the patients. Computed
      tomography angiography was performed in ten cases, which confirmed the diagnosis
      in all these cases. Magnetic resonance angiography was performed in only three
      patients. Renal scintigraphy was performed in 11 patients, with DTPA in nine
      patients and with MAG3 in two cases. Arteriography was performed in 15 cases for
      therapeutic end points. In two patients, we treated the arteries of both kidneys
      and in 19 cases we treated only one kidney artery. Percutaneous transluminal
      angioplasty was performed in ten cases. Renal arterial stent placement was
      performed in three cases in which RAS was from an atherosclerosis etiology.
      Surgical revascularization was performed in four cases. Nephrectomy was necessary
      in four cases. After interventional treatment, medical treatment using
      antihypertensive drugs was necessary in 17 of the patients. After treatment,
      three patients returned to normal kidney function, while worsening of glomerular
      filtration rate was noted in four patients. Some complications such as a kidney
      infarct after treatment, a nephrectomy, artery thrombosis, an ischemic stroke and
      recurrent RAS were also noted. 

PMID- 24434390
TI  - Recurrent renal allograft dysfunction due to ureteric stenosis in a patient with
      the BK virus infection.
AB  - Diseases of the genitourinary tract in association with the BK virus (BKV)
      infection are increasing among renal allograft recipients. We herewith report a
      young, female renal transplant recipient who presented with allograft dysfunction
      secondary to proximal ureteric stenosis. The allograft function improved
      dramatically after correction and stenting of the stenosis. Our case suggests
      that screening for BKV infection should be an integral part of evaluation of
      allograft dysfunction.

PMID- 24434391
TI  - Leak from the surface of a decapsulated renal allograft: urine or lymph?
      Excellent response to povidone iodine instillation.

PMID- 24434392
TI  - Forgotten ureteric stents in renal transplant recipients: three case reports.
AB  - Ureteric stents are widely used in renal transplantation to minimize the early
      urological complications. Ureteric stents are removed between two and 12 weeks
      following trans-plantation, once the vesico-ureteric anastomosis is healed.
      Ureteric stents are associated with considerable morbidity due to complications
      such as infection, hematuria, encrustations and migration. Despite the patient
      having a regular follow-up in the renal transplant clinic, ureteric stents may be
      overlooked and forgotten. The retained or forgotten ureteric stents may adversely
      affect renal allograft function and could be potentially life-threatening in
      immunocompromised transplant recipients with a single transplant kidney.
      Retrieving these retained ureteric stents could be challenging and may
      necessitate multimodal urological treatments. We report three cases of forgotten
      stents in renal transplant recipients for more than four years. These cases
      emphasize the importance of patient education about the indwelling ureteric stent
      and possibly providing with a stent card to the patient. Maintaining a stent
      register, with a possible computer tracking system, is highly recommended to
      prevent such complications. 

PMID- 24434393
TI  - Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a
      renal transplant recipient.
AB  - Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive
      states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion.
      We report a case of secondary hyperoxaluria in which the diagnosis was not
      considered initially because there was no past history of urinary calculi and no
      evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography.
      The disease was detected and diagnosed only after kidney transplantation.
      Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the
      allograft should be carefully examined for oxalate deposits even in the absence
      of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD)
      to eliminate calcium oxalate can help in the recovery of renal function in some
      cases. Systematic vitamin C supplementation in HD patients should be avoided as
      it can be a cause of secondary oxalosis. 

PMID- 24434394
TI  - Recurrent epistaxis revealing a non-catheter-related superior vena cava syndrome
      in a hemodialysis patient: unmasking undifferentiated connective tissue disease.
AB  - We report a case of an 80-year-old Caucasian woman on maintenance hemodialysis
      for almost three years through a right-tunneled jugular catheter. She presented
      with recurrent epistaxis for which she was periodically blood transfused despite
      erythropoietin therapy. She continued manifesting epistaxis, which was
      progressively emerging as a sign related to superior vena cava syndrome due to
      mediastinal mass. Laboratory investigations revealed active immunological
      abnormalities thereafter. Malignant superior vena syndrome remains an uncommon
      com-plication in this population related to a history of or ongoing central vein
      catheterization. Prolonged oozing from the vascular site was the first alerting
      sign of the existence of this syndrome. We conclude that sometimes the
      transformation of undifferentiated connective tissue disease in the presence of
      epidermoid carcinoma of the superior mediastinum may be revealed during the use
      of catheters in dialysis.

PMID- 24434395
TI  - Acute renal failure and severe thrombocytopenia associated with metamizole.
AB  - Metamizole or dipyrone is a pyrazolone derivative that belongs to the non
      steroidal anti-inflammatory drugs. Its main side-effect is hematological
      toxicity. Thrombocytopenia due to metamizole is rare and is usually associated
      with the involvement of the two other blood series. Drug-induced thrombocytopenia
      is more frequently related to immune mechanisms, and the diagnosis is still
      largely made by exclusion of other causes and by correlation of timing of
      thrombocytopenia with the administration of drug. Metamizole may cause acute
      renal failure due to hemodynamic renal failure/acute tubular necrosis and/or
      acute tubulointerstitial nephritis. We report a case of acute renal failure and
      severe thrombocytopenia after metamizole. As far as we know, this combination of
      adverse effects from this drug has not been reported previously.

PMID- 24434396
TI  - Multiple cysts in kidneys: a case report.
AB  - Von Hippel-Lindau (VHL) disease, which is an autosomal dominant inherited
      disease, is characterized by highly vascularized tumors in different organs. We
      report a 42-year-old male who presented to our hospital with diarrhea and weight
      loss of six months' duration. Ultrasonography of the abdomen revealed bilateral
      polycystic kidneys with multiple cystic and solid components as well as
      polycystic pancreas. A computerized tomography scan of the abdomen revealed
      bilateral multiple simple and complex renal cysts, cystic lesions in the head and
      body of the pancreas and a non-enhancing lesion in the left adrenal gland. The
      features raised the possibility of VHL syndrome and a biopsy of the kidney
      revealed atypical cells with a suspicion of malignancy. He underwent bilateral
      nephrectomy and is on maintenance dialysis since then.

PMID- 24434397
TI  - Tranexamic acid overdosage-induced generalized seizure in renal failure.
AB  - We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic
      tubulointerstial disease. She was admitted to our center for severe anemia due to
      menorrhagia and deterioration of renal function. She was infused three units of
      packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly
      was administered to her to control bleeding per vaginum. Two hours after the
      sixth dose of TNA, she had an episode of generalized tonic clonic convulsions.
      TNA was discontinued. Investigations of the patient revealed no biochemical or
      structural central nervous system abnormalities that could have provoked the
      convulsions. She did not require any further dialytic support. She had no further
      episodes of convulsion till dis-charge and during the two months of follow-up.
      Thus, the precipitating cause of convulsions was believed to be an overdose of
      TNA. 

PMID- 24434398
TI  - Adaptation and implementation of the "Kidney Disease: Improving Global Outcomes
      (KDIGO)" guidelines for evaluation and management of mineral and bone disorders
      in chronic kidney disease for practice in the Middle East countries.
AB  - This review presents the views of an expert group of nephrologists from the
      Middle East along with an international expert on adaptation and implementation
      of the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for
      evaluation and manage-ment of mineral and bone disorders in chronic kidney
      disease (CKD-MBD) for practice in the Middle East countries. The members of the
      panel examined the KDIGO guidelines and formulated recommendations that can be
      implemented practically for the management of CKD-MBD in the Middle East. There
      was a broad agreement on most of the recommendations made by the KDIGO work
      group. However, the panelists commented on specific areas and amplified certain
      concepts that might help the nephrologists in the Middle East. The final document
      was reviewed by all participants as well as by members of the Middle East task
      force implementation group for KDIGO guidelines. Their comments were
      incorporated. The guideline statements are presented along with detailed
      rationale and relevant discussion as well as limitations of the evidence. The
      panel recognized the need to upgrade the suggestion of KDIGO related to lateral
      abdominal radiograph and echocardiogram in patients with CKD stages 3-5D into a
      stronger recommendation. The panel underlined the risk of hyper-phosphatemia to
      CKD-MBD and the importance of prompt initiation or modification of therapy
      according to rising trends in para-thyroid hormone level. They recommended the
      use of non-calcium-based phosphate binders as the first-line therapy in CKD
      patients with signs of vascular calcification. The panel agreed that all aspects
      of the KDIGO recommendations concerning bone biopsy, evaluation and treatment of
      bone disease after kidney trans-plantation should be implemented as such. 

PMID- 24434399
TI  - Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a
      renal transplant recipient.

PMID- 24434400
TI  - Dengue transmission via transplantation: need further evidence.

PMID- 24434401
TI  - Inguinal herniation of the bladder and ureter: an unusual cause of obstructive
      uropathy in a transplant kidney.

PMID- 24434402
TI  - Polyflux(r) 210H hemodialysis membrane targets to improve filtration.

PMID- 24434403
TI  - Factors affecting the maturation of arterio-venous fistula in patients with end
      stage renal disease.

PMID- 24434404
TI  - Adding peritoneal flush for catheter salvage after early CAPD peritonitis: a
      report of two cases.

PMID- 24434405
TI  - Half and half nail.

PMID- 24434406
TI  - Inverted cortico-medullary differentiation of renal hemosiderosis.

PMID- 24434407
TI  - Creatinine clearance of strict vegetarianism practitioners: an observation.

PMID- 24434408
TI  - Prevalence of hypertension in healthy school children in Pakistan and its
      relationship with body mass index, proteinuria and hematuria.

PMID- 24434409
TI  - Metabolic status of 1088 patients after renal transplantation: assessment of
      twelve years monitoring in Algiers Mustapha Hospital.
AB  - Since the introduction of monitoring levels of immunosuppressive medications in
      our service in July 2000, 1088 kidney transplant patients were received for
      therapeutic drug monitoring and regular follow-up. The aim of this study was to
      retrospectively analyze the data on these renal graft patients in Algeria and
      correlate with our 12 years' experience with calcineurin inhibitor (CNI)
      measurements. In addition, during this period, we also examined other bioche
      mical parameters. The analysis was focused on the difference of effect of
      cyclosporin A (CsA; 623 patients) and Tacrolimus (Tac; 465 patients) on lipid and
      glucose metabolism and their side-effects, if any, on the renal function. The
      mean age at the time of transplantation was 36.1 years. A great majority of the
      transplanted kidneys had been taken from living related donors (88.6%). Three
      quarters of all grafts were transplanted in our country (79.5%). Dyslipidemia and
      renal dysfunction were the most common adverse effects of CsA and Tac exposure,
      with a frequency of 21.4% and 10.3%, respectively. Both the CNIs had a similar
      effect on the lipid levels. The highest incidence occurred at 3-12 months after
      renal graft. Tac seemed to have more side-effects on glycemia, causing the onset
      of diabetes mellitus more than two-fold than CsA (6.9% vs. 3.1%). A significant
      difference was observed during 12-24 months after transplantation. However, Tac
      was associated with the most favorable effects on renal function estimated with
      the Modification of Diet in Renal Disease (MDRD) formula. 

PMID- 24434410
TI  - Factors affecting response to hepatitis B vaccine among hemodialysis patients in
      a large Saudi Hemodialysis Center.
AB  - The aim of this study is to determine the response to hepatitis B virus (HBV)
      vaccination in patients on hemodialysis (HD) and to identify the factors that
      could affect this response. This retrospective study was carried out during the
      period from January 2009 to December 2009 in the Prince Salman Center for Kidney
      Diseases (PSCKD), Riyadh, and included 144 patients (78 males and 66 females) on
      regular HD, all of whom received hepatitis B vacci-nation. Patients were divided
      into two groups according to the level of hepatitis B surface antibodies (HBsAb):
      Responders group (>10 IU/L) and non-responders group (<10 IU/L). The study looked
      at the factors that may affect the responsiveness to hepatitis B vaccination,
      like gender, age, co-existence of hepatitis C virus (HCV) infection, dialysis
      adequacy that was evaluated by urea reduction ratio (URR) and Kt/V, hemoglobin
      level, albumin level, protein catabolic rate (PCR), body mass index (BMI),
      subjective global nutritional status (SGA) and HbA1c. There were 129 patients
      (89.6%) in the responders group including 69 males and 60 females and 15 patients
      (10.4%) in the non-responders group including nine males and six females. The
      mean age in the responders group and the non-responders group was 50.56 +/- 15.35
      and 56.87 +/- 12.52 years, respectively (P = 0.128). The mean value of the PCR
      was 1.03 +/- 0.17 and 0.88 +/- 0.17 g/kg/day in the responders group and non
      responders group, respectively (P = 0.002). There was no statically significant
      difference between the two groups regarding the presence or absence of HCV
      infection, age, gender, diabetes mellitus, URR, Kt/V, hemoglobin level and
      albumin level. We report a high response rate (89%) for HBV vaccination in our HD
      patients. The PCR was the only factor that affected the response to HBV
      vaccination in these patients. 

PMID- 24434411
TI  - End-stage renal disease in Tabuk Area, Saudi Arabia: an epidemiological study.
AB  - The purpose of this study was to determine the prevalence, etiology and risk
      factors of treated end-stage renal disease (ESRD) in the region of Tabuk, Saudi
      Arabia. We studied 460 renal replacement therapy patients through a review of
      medical records and patient interviews and obtained patient demographics, family
      history, risk factors for ESRD, environmental exposure to toxins, work
      conditions, social history and causes of death. The estimated prevalence of
      treated ESRD was 460 per million populations (PMP); 350 (76%) were treated by
      hemodialysis, 30 (7%) by peritoneal dialysis and 80 (17%) by kidney
      transplantation. The mean age was 48 +/- 17 years, body mass index was 25 +/- 2
      kg/m 2 and the male vs. female ratio was 64% vs. 36%. Most patients (55%) were
      living in rural areas. Etiology of the ESRD was unknown in 33%, hypertension in
      24%, chronic glomerulonephritis in 8%, obstructive uropathy in 3.5%, analgesic
      nephropathy in 5%, Bilhaziasis in 0.5%, chronic pyelonephritis in 2% and diabetic
      nephropathy in 18%. Other causes such as gouty nephropathy, collagen diseases,
      toxemia of pregnancy and lupus nephritis constituted 6% of the cases. We conclude
      that the epidemiology of the treated ESRD in Tabuk area is similar to that in
      Egypt, but very different from that in the United States.

PMID- 24434412
TI  - Predictors of public attitude toward living organ donation in Kano, northern
      Nigeria.
AB  - Organ shortage is a major public health challenge for transplant programs
      globally. The sustenance of such programs as an effective therapy for end-stage
      organ failure (ESOF) requires an exploration of public awareness and willingness
      to donate organs. This is imperative, especially in developing countries where
      ESOF is highly prevalent. We studied the awareness and predictors of public
      attitude toward organ donation in Kano city in northern Nigeria. Using
      interviewer-administered questionnaires, we assessed the awareness and
      willingness to donate solid organs among 400 adults in the Kano metropolis. Three
      hundred and five of the 383 respondents (79.6%) reported that they had heard
      about organ donation. There was a significant variation of awareness by education
      and ethnicity (P <0.05). Most respondents, 303 (79.1%), were willing to donate an
      organ. Gender [adjusted odds ratio (AOR) = 2.13; 95% confidence interval (CI):
      1.40-4.95], educational attainment (AOR = 2.55; 95% CI: 1.35-5.88), marital
      status (AOR = 4.5; 95% CI: 2.97-9.1), religion (AOR = 3.40; 95% CI: 1.43-8.10)
      and ethnicity (AOR = 2.36; 95% CI 1.04-5.35) were significant predictors of
      willingness to donate an organ. Preferred organ recipients were parents (48.9%),
      children (21.3%), spouses (14.6%) and other relatives (13.4%). Reasons for
      willingness to donate organs included religion (51.2%), moral obligation (21.4%)
      and compassion (11.9%), among others. However, there was widespread ignorance of
      religious precepts concerning organ donation. The high level of awareness and
      willingness to donate organs in this society could be further enhanced by
      intensive information, education and communication strategies providing clear
      messages on societal benefits, religious aspects and bioethical guidance
      regarding organ donation. 

PMID- 24434413
TI  - Precordial vibrations provide noninvasive detection of early-stage hemorrhage.
AB  - Graded lower-body negative pressure was used to create a hemodynamic response
      similar to hemorrhage. Echocardiogram measurements showed a maximal reduction of
      32.4% in stroke volume. Analysis of systolic time intervals, such as pre-ejection
      period and left ventricular ejection time (LVET), derived from a seismocardiogram
      (SCG), were demonstrated to be more sensitive in detection of early-stage
      hemorrhage compared with pulse pressure, heart rate, and the amplitude features
      extracted from SCG. In particular, the LVET and pre-ejection period/LVET
      features, extracted from SCG, were significantly different between, and
      correlated with, the different stages of lower-body negative pressure (r = 0.9
      and 0.88, P < 0.05), for 32 subjects. These results suggest a portable, cost
      effective solution for identification of mild or moderate hemorrhage using
      accelerometers. 

PMID- 24434414
TI  - Lipid-rich enteral nutrition improves the defense against an opportunistic
      infection during polymicrobial sepsis.
AB  - The development of an immunosuppressive state during the protracted course of
      sepsis is associated with opportunistic infections and is considered to correlate
      with the extent of the proinflammatory response during early sepsis. Short-term
      intervention with enteral lipid-rich nutrition was shown to attenuate the acute
      inflammatory response. This study investigates the effects of lipid-rich
      nutrition on the immunosuppression induced by polymicrobial sepsis. Female BALB/c
      mice were either fasted or fed liquid lipid-rich nutrition or isocaloric control
      nutrition before and shortly after induction of polymicrobial sepsis through
      cecal ligation and puncture (CLP) or sham operation. After 4 days, mice were
      intranasally infected with Pseudomonas aeruginosa. Twenty-four hours after P.
      aeruginosa infection, fasted and control nutrition-fed CLP mice displayed a
      significantly higher bacterial load in the lungs than did corresponding sham
      operated mice (P < 0.001 and P < 0.05, respectively). Fasted CLP mice expressed
      reduced pulmonary levels of proinflammatory cytokines interleukin 12 (IL-12) and
      interferon gamma (IFN-gamma) in comparison to sham mice (both P < 0.05). Lipid
      rich nutrition prevented the increase in bacteria, promoted the IL-12 and IFN
      gamma production (IL-12 and IFN-gamma [P < 0.05] vs. fasted and IFN-gamma [P <
      0.05] vs. control nutrition), and prevented the expression of the
      immunosuppressive cytokine IL-10 (P < 0.05 vs. control nutrition) in lungs of CLP
      mice. The preserved immune defense during late sepsis in lipid-rich fed mice was
      preceded by attenuation of the early inflammatory response (IL-6 [P = 0.05] and
      IL-10 [P < 0.01] vs. fasted CLP mice) at 6 h after CLP. In conclusion, short-term
      treatment with lipid-rich enteral nutrition improves the pulmonary antimicrobial
      defense during polymicrobial sepsis. 

PMID- 24434415
TI  - Glutamine administration modulates lung gammadelta T lymphocyte expression in
      mice with polymicrobial sepsis.
AB  - This study investigated the effects of glutamine (GLN) administration on
      regulating lung gammadelta T cells in polymicrobial sepsis. Mice were randomly
      assigned to normal group (NC), septic saline group (SS), and septic GLN group
      (SG). All mice were fed with chow diet. Sepsis was induced by cecal ligation and
      puncture (CLP). The SS and SG groups were, respectively, injected with saline and
      0.75 g GLN/kg body weight once via tail vein 1 h after CLP. Mice were killed 12
      and 24 h after CLP. Their lungs were collected for further analysis. The results
      showed that, compared with normal mice, sepsis resulted in higher lung gammadelta
      T cell and neutrophil percentages and higher cytokine expressed by gammadelta T
      cells. Histopathologic findings showed that the extent of inflammatory lesions of
      the lung alveolar was less severe in the SG group than the SS group after CLP.
      The SG group had a higher gammadelta T cell percentage and lower gammadelta T
      cell apoptotic rates as well as lower neutrophil numbers in the lungs. Also,
      interleukin 17A (IL-17A), interferon gamma, and IL-10 expressed by gammadelta T
      cells and CXC receptor 2 expressed by neutrophils decreased in the SG group.
      Moreover, GLN reduced IL-17A, IL-1beta, and IL-23 concentrations and
      myeloperoxidase activity in lung tissues. Our results suggest that GLN
      administration after initiation of sepsis affects lung gammadelta T cell
      percentage and cytokine secretion and prevented apoptosis of gammadelta T cells
      and neutrophil infiltration to the lungs, which may partly be responsible for
      ameliorating acute lung injury induced by sepsis. 

PMID- 24434417
TI  - Estrus cycle status defined by vaginal cytology does not correspond to
      fluctuations of circulating estrogens in female mice.
AB  - Gender-oriented studies in shock, trauma, and/or sepsis require accurate
      monitoring of hormonal fluctuations as estrogens may influence various end
      points. Yet, monitoring is challenging in small laboratory animals: e.g., despite
      its subjectivity, vaginal smears are the major method for determination of estrus
      cycle phases in mice. Using female mice of different age, we aimed to (a)
      characterize general age-related changes in systemic estrogens and (b) examine
      the utility of determination of the estrus cycle by vaginal smears and/or
      impedance simultaneously comparing them with oscillation of systemic estrogens.
      In this study, 3-, 15-, and 20-month-old mice underwent vaginal smear and
      impedance examination each morning for 22 days. Ten hours after each morning
      checkup, feces were collected, and a second vaginal smear performed. Blood was
      collected on days 15 and 22. In 3-month-old females, estrus (by smears) was three
      times more frequent than in older mice, but mean concentrations of plasma and
      fecal estrogens never decreased with age. Collectively (not individually) plotted
      fecal estrogens values increased in the proestrus/estrus interphase (by smears)
      in 3-month-old mice only. Impedance typically peaked (4.5 Omega in 3-month-old
      mice) in the estrus phase, and only the prediction of estrus (highest area under
      the curve = 0.87 in 3-month-old) but not of other phases was possible. Regardless
      of age, individual cycle phase (by smears) never correlated with corresponding
      fecal estrogens, and estrus could not be predicted. In conclusion, while the
      fecal estrogens oscillation and frequency of estrus phase were affected by age,
      the systemic hormone release persisted. In mice, vaginal cytology did not reflect
      changes of systemic (fecal) estrogens, whereas impedance accurately identified
      estrus. The flaws and advantages of the examined monitoring methods should be
      considered in the design of future shock studies. 

PMID- 24434416
TI  - Burn plus lipopolysaccharide augments endoplasmic reticulum stress and NLRP3
      inflammasome activation and reduces PGC-1alpha in liver.
AB  - Extensively burned patients often suffer from sepsis (especially caused by
      Pseudomonas aeruginosa), which may prolong metabolic derangement, contribute to
      multiple organ failure, and increase mortality. The molecular and cellular
      mechanisms of such infection-related metabolic derangement and organ dysfunction
      are unclear. We have previously shown that severely burned patients have
      significant and persisting hepatic endoplasmic reticulum (ER) stress. We
      hypothesized that ER stress and the unfolded protein response correlate with NOD
      like receptor, pyrin domain containing 3 (NLRP3) inflammasome activation in burn.
      These may trigger profound metabolic changes in the liver, which form the
      pathological basis of liver damage and liver dysfunction after burn injury. A two
      hit rat model was established by a 60% total body surface area scald burn and
      intraperitoneal injection of P. aeruginosa-derived lipopolysaccharide (LPS) 3
      days after burn. One day later, animals were killed, and liver tissue samples
      were collected for gene expression and protein analysis of NLRP3 inflammasome
      activation, ER stress, and glucose and lipid metabolism. Liver damage was
      assessed by plasma markers (alanine aminotransferase and aspartate
      aminotransferase) and liver immunohistochemical analysis. Our results showed that
      burn injury and LPS injection induced inflammasome activation in liver and
      augmented hepatic ER stress and liver damage. Although there was an increased
      metabolic demand after burn, hepatic NLRP3 inflammasome activation corresponded
      to inhibition of PGC-1alpha (peroxisome proliferator-activated receptor gamma
      coactivator 1alpha) and its upstream regulators protein kinase A catalyst unit,
      AMP-activated protein kinase alpha, and sirtuin-1 may provide a mechanism for the
      enhanced metabolic derangement after major burn injury plus sepsis. In
      conclusion, burn + LPS augments inflammasome activation and ER stress in liver,
      which in turn contribute to postburn metabolic derangement. 

PMID- 24434418
TI  - Comparative effect of hypothermia and adrenaline during cardiopulmonary
      resuscitation in rabbits.
AB  - BACKGROUND: Therapeutic hypothermia was shown to facilitate resumption of
      spontaneous circulation when instituted during cardiac arrest. Here, we
      investigated whether it directly improved the chance of successful resuscitation
      independently of adrenaline administration in rabbits. We further evaluated the
      direct effect of hypothermia on vascular function in vitro. METHODS: In a first
      set of experiments, four groups of anesthetized rabbits were submitted to 15 min
      of cardiac arrest and subsequent cardiopulmonary resuscitation (CPR). The
      "control" group underwent CPR with only cardiac massage and defibrillation
      attempts. Two other groups received cold or normothermic saline infusion during
      CPR (20 mL/kg of NaCl 0.9% at 4 degrees C or 38 degrees C, respectively). In a
      last group, the animals received adrenaline (15 ug/kg intravenously) during CPR.
      In a second set of experiments, we evaluated at 32 degrees C vs. 38 degrees C the
      vascular function of aortic rings withdrawn from healthy rabbits or after cardiac
      arrest. RESULTS: In the first set of experiments, cardiac massage efficiency was
      improved by adrenaline but neither by hypothermic nor normothermic saline
      administration. Resumption of spontaneous circulation was observed in five of
      eight animals after adrenaline as compared with none of eight in other groups.
      Defibrillation rates were conversely similar among groups (7/8 or 8/8). In the
      second set of experiments, in vitro hypothermia (32 degrees C) was not able to
      prevent the dramatic alteration of vascular function observed after cardiac
      arrest. It also did not directly modify vasocontractile or the vasodilating
      functions in healthy conditions. CONCLUSION: In rabbits, hypothermia did not
      exert a direct hemodynamic or vascular effect that might explain its beneficial
      effect during CPR.

PMID- 24434419
TI  - Midterm effects of fluid resuscitation strategies in an experimental model of
      lung contusion and hemorrhagic shock.
AB  - BACKGROUND: This study compared three different fluid resuscitation strategies in
      terms of respiratory tolerance and hemodynamic efficacy in a pig model of blunt
      chest trauma with lung contusion and controlled hemorrhagic shock. We
      hypothesized that the choice of fluid resuscitation strategy (type and amount of
      fluids) may impact differently contused lungs in terms of extravascular lung
      water (EVLW) 20 h after trauma. METHODS: Anesthetized female pigs (n = 5/group)
      received five bolt shots to the right thoracic cage and allowed to hemorrhage for
      30 min, with 25 to 30 mL/kg of blood loss. Pigs were randomly assigned to
      resuscitation groups that maintained a minimum mean arterial blood pressure of 70
      mmHg with one of three methods: normal saline (NS), unrestricted normal saline;
      NOREPI, low-volume normal saline with norepinephrine; or HS-HES, hypertonic
      saline with hydroxyethyl starch. Control pigs were anesthetized, but received no
      injury or treatment. After 20 h, animals were killed to measure EVLW by
      gravimetry. RESULTS: Fluid loading was significantly different in each group. All
      three treatment groups had higher EVLW than controls. Moderate, bilateral
      pulmonary edema was observed in the NS and HS-HES groups. The three treatment
      groups showed similar reductions in oxygenation. Static pulmonary compliance was
      diminished in the NS and HS-HES groups, but compliance was similar in NOREPI and
      control groups. The NOREPI group had pathological lactate levels. CONCLUSIONS:
      This study demonstrated the impact of fluid resuscitation on contused lungs.
      Twenty hours after the trauma, all three resuscitation approaches showed modest
      clinical consequences, with moderate lung edema and reduced compliance in
      response to the infused volume.

PMID- 24434420
TI  - In vivo evaluation of the elastic anisotropy of the human Achilles tendon using
      shear wave dispersion analysis.
AB  - Non-invasive evaluation of the Achilles tendon elastic properties may enhance
      diagnosis of tendon injury and the assessment of recovery treatments. Shear wave
      elastography has shown to be a powerful tool to estimate tissue mechanical
      properties. However, its applicability to quantitatively evaluate tendon
      stiffness is limited by the understanding of the physics on the shear wave
      propagation in such a complex medium. First, tendon tissue is transverse
      isotropic. Second, tendons are characterized by a marked stiffness in the 400 to
      1300 kPa range (i.e. fast shear waves). Hence, the shear wavelengths are greater
      than the tendon thickness leading to guided wave propagation. Thus, to better
      understand shear wave propagation in tendons and consequently to properly
      estimate its mechanical properties, a dispersion analysis is required. In this
      study, shear wave velocity dispersion was measured in vivo in ten Achilles
      tendons parallel and perpendicular to the tendon fibre orientation. By modelling
      the tendon as a transverse isotropic viscoelastic plate immersed in fluid it was
      possible to fully describe the experimental data (deviation<1.4%). We show that
      parallel to fibres the shear wave velocity dispersion is not influenced by
      viscosity, while it is perpendicularly to fibres. Elasticity (found to be in the
      range from 473 to 1537 kPa) and viscosity (found to be in the range from 1.7 to 4
      Pa.s) values were retrieved from the model in good agreement with reported
      results. 

PMID- 24434421
TI  - Isothiocyanate-cysteine conjugates protect renal tissue against cisplatin-induced
      apoptosis via induction of heme oxygenase-1.
AB  - Heme oxygenase-1 (HO-1) is a redox sensitive inducible enzyme endowed with
      important antioxidant and cytoprotective activities. Here we report that two
      water-soluble isothiocyanate-cysteine conjugates, S-[N-benzyl(thiocarbamoyl)]-l
      cysteine (BTTC) and S-[N-(3-phenylpropyl)(thiocarbamoyl)]-l-cysteine (PTTC),
      potently increase HO-1 protein expression and heme oxygenase activity in renal
      tubular epithelial cells at 5 and 10MUM, while higher concentrations are
      themselves cytotoxic and pro-apoptotic. Inhibitors of the pro-survival pathways
      ERK, MAPK and PI3K almost completely abolished the increase in HO-1 induction and
      heme oxygenase activity, while the JNK pathway appeared to be mainly involved in
      the apoptosis triggered by the isothiocyanates. We also found that renal cells
      exposed to 50MUM cisplatin (CDDP), a chemotherapeutic agent known for its
      nephrotoxic actions, displayed a marked increase in caspase-3 activity and the
      number of apoptotic cells. These effects were abolished by pre-incubation of
      cells with concentrations of BTCC or PTCC that maximize HO-1 induction and were
      reversed by the inhibitor of heme oxygenase activity tin protoporphyrin IX
      (SnPPIX). Moreover, in a model of CDDP-induced nephrotoxicity in vivo, pre
      treatment of rats with a daily dose of BTCC or PTCC (25mg/kg, i.p.) completely
      abolished the increase in serum creatinine and urea levels and markedly reduced
      the severity of renal tissue apoptosis caused by CDDP. The renoprotective effects
      of BTCC and PTCC in vivo were markedly attenuated by administration of rats with
      SnPPIX. These findings indicate that water-soluble isothiocyanates counteract
      renal dysfunction and apoptosis by up-regulating the HO-1 system and could be
      used as a supplementary treatment to mitigate CDDP-induced nephrotoxic effects. 

PMID- 24434422
TI  - Regeneration of calvarial defects with Escherichia coli -derived rhBMP-2 adsorbed
      in PLGA membrane.
AB  - OBJECTIVE: Escherichia coli-derived recombinant human bone morphogenetic protein
      2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2.
      However, several in vitro and in vivo experiments are still necessary to validate
      the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly
      related to protein nonglycosylation. The objective of this study was to
      investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a
      suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized
      defects in rat calvaria. MATERIALS AND METHODS: First, the osteoinductive effect
      of E-BMP-2 was confirmed in vitro in mouse bone marrow stromal cells by analysis
      of osteocalcin mRNA levels, and calcium deposition was detected by alizarin red
      staining. Before in vivo experiments, the release profile of E-BMP-2 from PLGA
      membranes was determined by ELISA. E-BMP-2 (0, 1, 5 and 10 MUg/MUl) was applied
      for ectopic and orthotopic bone formation and was analyzed by X-ray, micro-CT and
      histology. RESULTS: Release-profile testing showed that PLGA membrane could
      retain 94% of the initially applied E-BMP-2. Ectopic bone formation assay
      revealed that combination of E-BMP-2/PLGA membrane strongly induced bone
      formation. Stronger osteoinductivity with complete repair of critical-sized
      defects was observed only with PLGA membranes adsorbed with 5 and 10 MUg/MUl of E
      BMP-2, whereas no bone formation was observed in the groups that received no
      membrane or 0-MUg/MUl dose of E-BMP-2. CONCLUSION: PLGA membrane was shown to be
      a suitable carrier for sustained release of E-BMP-2, and the E-BMP-2/PLGA
      membrane combination was demonstrated to be efficient in bone regeneration in a
      model of critical-sized defects.

PMID- 24434423
TI  - Topical delivery of siRNA into skin using SPACE-peptide carriers.
AB  - Short-interfering RNAs (siRNAs) offer a potential tool for the treatment of skin
      disorders. However, applications of siRNA for dermatological conditions are
      limited by their poor permeation across the stratum corneum of the skin and low
      penetration into the skin's viable cells. In this study, we report the use of
      SPACE-peptide in combination with a DOTAP-based ethosomal carrier system to
      enhance skin delivery of siRNA. A DOTAP-based SPACE Ethosomal System
      significantly enhanced siRNA penetration into porcine skin in vitro by 6.3+/-1.7
      fold (p<0.01) with an approximately 10-fold (p<0.01) increase in epidermis
      accumulation of siRNA compared to that from an aqueous solution. Penetration of
      siRNA was also enhanced at the cellular level. Internalization of SPACE-peptide
      occurred in a concentration dependent manner marked by a shift in intracellular
      distribution from punctate spots to diffused cytoplasmic staining at a peptide
      concentration of 10mg/mL. In vitro delivery of GAPDH siRNA by SPACE peptide led
      to 83.3+/-3.0% knockdown relative to the control. In vivo experiments performed
      using female BALB/C mice also confirmed the efficacy of DOTAP-SES in delivering
      GAPDH-siRNA into skin. Topical application of DOTAP-SES on mice skin resulted in
      63.2%+/-7.7% of GAPDH knockdown, which was significantly higher than that from
      GAPDH-siRNA PBS (p<0.05). DOTAP-SES formulation reported here may open new
      opportunities for cutaneous siRNA delivery. 

PMID- 24434425
TI  - Sequence-based protein stabilization in the absence of glycosylation.
AB  - Asparagine-linked N-glycosylation is a common modification of proteins that
      promotes productive protein folding and increases protein stability. Although N
      glycosylation is important for glycoprotein folding, the precise sites of
      glycosylation are often not conserved between protein homologues. Here we show
      that, in Saccharomyces cerevisiae, proteins upregulated during sporulation under
      nutrient deprivation have few N-glycosylation sequons and in their place tend to
      contain clusters of like-charged amino-acid residues. Incorporation of such
      sequences complements loss of in vivo protein function in the absence of
      glycosylation. Targeted point mutation to create such sequence stretches at
      glycosylation sequons in model glycoproteins increases in vitro protein stability
      and activity. A dependence on glycosylation for protein stability or activity can
      therefore be rescued with a small number of local point mutations, providing
      evolutionary flexibility in the precise location of N-glycans, allowing protein
      expression under nutrient-limiting conditions, and improving recombinant protein
      production. 

PMID- 24434424
TI  - Accumulation, internalization and therapeutic efficacy of neuropilin-1-targeted
      liposomes.
AB  - Advancements in liposomal drug delivery have produced long circulating and very
      stable drug formulations. These formulations minimize systemic exposure; however,
      unfortunately, therapeutic efficacy has remained limited due to the slow
      diffusion of liposomal particles within the tumor and limited release or uptake
      of the encapsulated drug. Here, the carboxyl-terminated CRPPR peptide, with
      affinity for the receptor neuropilin-1 (NRP), which is expressed on both
      endothelial and cancer cells, was conjugated to liposomes to enhance the tumor
      accumulation. Using a pH sensitive probe, liposomes were optimized for specific
      NRP binding and subsequent cellular internalization using in vitro cellular
      assays. Liposomes conjugated with the carboxyl-terminated CRPPR peptide (termed C
      LPP liposomes) bound to the NRP-positive primary prostatic carcinoma cell line
      (PPC-1) but did not bind to the NRP-negative PC-3 cell line, and binding was
      observed with liposomal peptide concentrations as low as 0.16mol%. Binding of the
      C-LPP liposomes was receptor-limited, with saturation observed at high liposome
      concentrations. The identical peptide sequence bearing an amide terminus did not
      bind specifically, accumulating only with a high (2.5mol%) peptide concentration
      and adhering equally to NRP positive and negative cell lines. The binding of C
      LPP liposomes conjugated with 0.63mol% of the peptide was 83-fold greater than
      liposomes conjugated with the amide version of the peptide. Cellular
      internalization was also enhanced with C-LPP liposomes, with 80% internalized
      following 3h incubation. Additionally, fluorescence in the blood pool (~40% of
      the injected dose) was similar for liposomes conjugated with 0.63mol% of carboxyl
      terminated peptide and non-targeted liposomes at 24h after injection, indicating
      stable circulation. Prior to doxorubicin treatment, in vivo tumor accumulation
      and vascular targeting were increased for peptide-conjugated liposomes compared
      to non-targeted liposomes based on confocal imaging of a fluorescent cargo, and
      the availability of the vascular receptor was confirmed with ultrasound molecular
      imaging. Finally, over a 4-week course of therapy, tumor knockdown resulting from
      doxorubicin-loaded, C-LPP liposomes was similar to non-targeted liposomes in
      syngeneic tumor-bearing FVB mice and C-LPP liposomes reduced doxorubicin
      accumulation in the skin and heart and eliminated skin toxicity. Taken together,
      our results demonstrate that a carboxyl-terminated RXXR peptide sequence,
      conjugated to liposomes at a concentration of 0.63mol%, retains long circulation
      but enhances binding and internalization, and reduces toxicity. 

PMID- 24434426
TI  - Time-dependent risk of developing distant metastasis in breast cancer patients
      according to treatment, age and tumour characteristics.
AB  - BACKGROUND: Metastatic breast cancer is a severe condition without curative
      treatment. How relative and absolute risk of distant metastasis varies over time
      since diagnosis, as a function of treatment, age and tumour characteristics, has
      not been studied in detail. METHODS: A total of 9514 women under the age of 75
      when diagnosed with breast cancer in Stockholm and Gotland regions during 1990
      2006 were followed up for metastasis (mean follow-up=5.7 years). Time-dependent
      development of distant metastasis was analysed using flexible parametric survival
      models and presented as hazard ratio (HR) and cumulative risk. RESULTS: A total
      of 995 (10.4%) patients developed distant metastasis; the most common sites were
      skeleton (32.5%) and multiple sites (28.3%). Women younger than 50 years at
      diagnosis, with lymph node-positive, oestrogen receptor (ER)-negative, >20 mm
      tumours and treated only locally, had the highest risk of distant metastasis (0-5
      years' cumulative risk =0.55; 95% confidence interval (CI): 0.47-0.64). Women
      older than 50 years at diagnosis, with ER-positive, lymph node-negative and <=20
      mm tumours, had the same and lowest cumulative risk of developing metastasis 0-5
      and 5-10 years (cumulative risk=0.03; 95% CI: 0.02-0.04). In the period of 5-10
      years after diagnosis, women with ER-positive, lymph node-positive and >20-mm
      tumours were at highest risk of distant recurrence. Women with ER-negative
      tumours showed a decline in risk during this period. CONCLUSION: Our data show no
      support for discontinuation at 5 years of clinical follow-up in breast cancer
      patients and suggest further investigation on differential clinical follow-up for
      different subgroups of patients.

PMID- 24434427
TI  - CD44 targets Na(+)/H(+) exchanger 1 to mediate MDA-MB-231 cells' metastasis via
      the regulation of ERK1/2.
AB  - BACKGROUND: CD44, a transmembrane glycoprotein expressed in a variety of cells
      and tissues, has been implicated in tumour metastasis. But the molecular
      mechanisms of CD44-mediated tumour cell metastasis remain to be elucidated.
      METHODS: The downregulation of CD44 was determined by immunofluorescence.
      Moreover, the motility of breast cancer cells was detected by wound-healing and
      transwell experiments. Then the spontaneous metastasis of CD44-silenced MDA-MB
      231 cells was tested by histology with BALB/c nude mice. RESULTS: A positive
      correlation between CD44 and Na(+)/H(+) exchanger isoform 1 (NHE1) was found in
      two breast cancer cells. CD44 downregulation could inhibit the metastasis of MDA
      MB-231 cells and the expressions of Na(+)/H(+) exchanger 1. Moreover, CD44
      overexpression upregulated the metastasis of MCF-7 cells, but the elevated
      metastatic ability was then inhibited by Cariporide. Interestingly, during these
      processes only the p-ERK1/2 was suppressed by CD44 downregulation and the
      expression of matrix metalloproteinases and metastatic capacity of MDA-MB-231
      cells were greatly inhibited by the MEK1 inhibitor PD98059, which even had a
      synergistic effect with Cariporide. Furthermore, CD44 downregulation inhibits
      breast tumour outgrowth and spontaneous lung metastasis. CONCLUSIONS: Taken
      together, this work indicates that CD44 regulates the metastasis of breast cancer
      cells through regulating NHE1 expression, which could be used as a novel strategy
      for breast cancer therapy.

PMID- 24434428
TI  - Host genetic variants of ABCB1 and IL15 influence treatment outcome in paediatric
      acute lymphoblastic leukaemia.
AB  - BACKGROUND: Host germline variations and their potential prognostic importance is
      an emerging area of interest in paediatric ALL. METHODS: We investigated the
      associations between 20 germline variations and various clinical end points in
      463 children with ALL. RESULTS: After adjusting for known prognostic factors,
      variants in two genes were found to be independently associated with poorer EFS:
      ABCB1 T/T at either 2677 (rs2032582) or 3435 (rs1045642) position (P=0.003) and
      IL15 67276493G/G (rs17015014; P=0.022). These variants showed a strong additive
      effect affecting outcome (P<0.001), whereby patients with both risk genotypes had
      the worst EFS (P=0.001), even after adjusting for MRD levels at the end of
      remission induction. The adverse effect of ABCB1 T/T genotypes was most
      pronounced in patients with favourable cytogenetics (P=0.011) while the IL15
      67276493G/G genotype mainly affected patients without common chromosomal
      abnormalities (P=0.022). In both cytogenetic subgroups, increasing number of such
      risk genotypes still predicted worsening outcome (P<0.001 and=0.009,
      respectively). CONCLUSION: These results point to the prognostic importance of
      host genetic variants, although the specific mechanisms remain unclarified.
      Inclusion of ABCB1 and IL15 variants may help improve risk assignment strategies
      in paediatric ALL.

PMID- 24434429
TI  - Circulating fibrinogen is a prognostic and predictive biomarker in malignant
      pleural mesothelioma.
AB  - BACKGROUND: To investigate the clinical utility of pretreatment plasma fibrinogen
      levels in malignant pleural mesothelioma (MPM) patients. METHODS: A retrospective
      multicenter study was performed in histologically proven MPM patients. All
      fibrinogen levels were measured at the time of diagnosis and clinical data were
      retrospectively collected after approval of the corresponding ethics committees.
      RESULTS: In total, 176 MPM patients (mean age: 63.5 years +/- 10.4 years, 38
      females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated
      (>= 390 mg dl(-1)) plasma fibrinogen levels. When patients were grouped by median
      fibrinogen, patients with low level (<= 627 mg dl(-1)) had significantly longer
      overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months)
      when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In
      multivariate survival analyses, fibrinogen was found to be an independent
      prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly,
      fibrinogen (cutoff 75th percentile per 750 mg dl(-1)) proved to be a predictive
      biomarker indicating treatment benefit achieved by surgery within multimodality
      therapy (interaction term: P=0.034). Accordingly, only patients below the 75th
      percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months
      OS). CONCLUSIONS: Fibrinogen is a novel independent prognostic biomarker in MPM.
      Most importantly, fibrinogen predicted treatment benefit achieved by surgery
      within multimodality therapy.

PMID- 24434430
TI  - Phase I study of panobinostat and imatinib in patients with treatment-refractory
      metastatic gastrointestinal stromal tumors.
AB  - BACKGROUND: Panobinostat, a pan-deacetylase inhibitor, overcomes imatinib
      resistance in preclinical models of gastrointestinal stromal tumours (GIST). Here
      we determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT)
      of panobinostat in combination with imatinib (IM) for treatment of patients with
      refractory GIST. METHODS: Following a 7-day run-in phase of IM (400 mg per day),
      escalating doses of panobinostat were added following a '3 plus 3' design. Twelve
      heavily pretreated GIST patients were enrolled in two dose levels. RESULTS: Most
      common adverse events were thrombocytopenia, anaemia, fatigue, creatinine
      elevation, nausea, emesis and diarrhoea. Twenty micrograms of panobinostat and
      400 mg IM were declared the MTD. Pharmacologically active concentrations of
      panobinostat and IM were achieved as evidenced by histone H3 acetylation in blood
      mononuclear cells in vivo and inhibition of the IM-resistant KIT (D816) mutation
      in vitro. In FDG-PET-CT scans after IM run-in and following 3 weeks panobinostat
      treatment, 1 out of 11 evaluable patients showed a metabolic partial response, 7
      patients were metabolically stable and 3 patients progressed. Longest treatment
      duration was 17 weeks (median 6). CONCLUSION: Panobinostat and IM can be
      administered at doses achieving target inhibition in vivo. Further clinical
      exploration of patients with treatment-refractory GIST is warranted. Correlative
      studies in this trial may help to optimise dosing schedules in GIST.

PMID- 24434431
TI  - Molecular heterogeneity and prognostic implications of synchronous advanced
      colorectal neoplasia.
AB  - BACKGROUND: It is uncertain whether synchronous colorectal cancers (S-CRCs)
      preferentially develop through widespread DNA methylation and whether they have a
      prognosis worse than solitary CRC. As tumours with microsatellite instability
      (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this
      issue in a series of CRC characterised by BRAF and MS status. METHODS:
      Demographics, clinicopathological records and disease-specific survival (DSS)
      were assessed in 881 consecutively resected CRC undergoing complete colonoscopy.
      All tumours were typed for BRAF(c.1799T>A) mutation and MS status, followed by
      search of germ-line mutation in patients with MSI CRC. RESULTS: Synchronous
      colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite
      stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001).
      BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%,
      P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer
      (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95%
      CI 1.27-2.58; P=0.001), and BRAF(c.1799T>A) mutation (HR 2.16; 95% CI 1.25-3.73;
      P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific
      survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09
      5.75; P=0.77). CONCLUSION: Microsatellite-stable CRCs have a worse prognosis if S
      CRC or synchronous advanced adenoma are diagnosed. The occurrence and the
      enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated
      with BRAF mutation.

PMID- 24434432
TI  - Piperlongumine promotes autophagy via inhibition of Akt/mTOR signalling and
      mediates cancer cell death.
AB  - BACKGROUND: The Akt/mammalian target of rapamycin (mTOR) signalling pathway
      serves as a critical regulator of cellular growth, proliferation and survival.
      Akt aberrant activation has been implicated in carcinogenesis and anticancer
      therapy resistance. Piperlongumine (PL), a natural alkaloid present in the fruit
      of the Long pepper, is known to exhibit notable anticancer effects. Here we
      investigate the impact of PL on Akt/mTOR signalling. METHODS: We examined
      Akt/mTOR signalling in cancer cells of various origins including prostate, kidney
      and breast after PL treatment. Furthermore, cell viability after concomitant
      treatment with PL and the autophagy inhibitor, Chloroquine (CQ) was assessed. We
      then examined the efficacy of in vivo combination treatment using a mouse
      xenograft tumour model. RESULTS: We demonstrate for the first time that PL
      effectively inhibits phosphorylation of Akt target proteins in all tested cells.
      Furthermore, the downregulation of Akt downstream signalling resulted in decrease
      of mTORC1 activity and autophagy stimulation. Using the autophagy inhibitor, CQ,
      the level of PL-induced cellular death was significantly increased. Moreover,
      concomitant treatment with PL and CQ demonstrated notable antitumour effect in a
      xenograft mouse model. CONCLUSIONS: Our data provide novel therapeutic
      opportunities to mediate cancer cellular death using PL. As such, PL may afford a
      novel paradigm for both prevention and treatment of malignancy.

PMID- 24434433
TI  - Chronic fatigue in Hodgkin lymphoma survivors and associations with anxiety,
      depression and comorbidity.
AB  - BACKGROUND: Fatigue is a frequent and persistent problem among Hodgkin lymphoma
      (HL) survivors. We investigated the prevalence of clinically relevant fatigue in
      HL survivors and the relation between fatigue and anxiety and depression.
      METHODS: Fatigue was measured through the generic European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and
      Fatigue Assessment Scale (FAS). Anxiety and depression were measured with the
      Hospital Anxiety and Depression Scale. Questionnaires were mailed to 267 HL
      survivors. Results were compared with a Dutch age-matched normative population.
      RESULTS: Response rate was 68% (median age 46 years, mean time since diagnosis
      4.6 years). Prevalence of fatigue was significantly higher among HL survivors
      than in the norm population (FAS 41% vs 23%, QLQ-C30 43% vs 28%), as were fatigue
      levels. There was a significant association between fatigue, anxiety and
      depression. Of the HL survivors with high symptom levels of depression, 97% also
      reported fatigue. In multivariate analysis, depression was strongly associated
      with high levels of fatigue and, to a lesser extent, anxiety and comorbidity.
      CONCLUSIONS: Prevalence rates of fatigue are significantly higher in HL survivors
      than in the general population and differences are clinically relevant.
      Depression and anxiety were strongly associated with high levels of fatigue.
      Reducing fatigue levels by treatment of depression and anxiety should be further
      explored.

PMID- 24434434
TI  - Efficacy and safety of sunitinib in elderly patients with metastatic renal cell
      carcinoma.
AB  - BACKGROUND: We retrospectively analyzed sunitinib outcome as a function of age in
      metastatic renal cell carcinoma (mRCC) patients. METHODS: Data were pooled from
      1059 patients in six trials. Kaplan-Meier estimates of progression-free survival
      (PFS) and overall survival (OS) were compared by log-rank test between patients
      aged <70 (n=857; 81%) and >=70 (n=202; 19%) years. RESULTS: In first-line
      patients, median PFS was comparable in younger and older patients, 9.9 vs 11.0
      months, respectively (HR, 0.89; 95% CI: 0.73-1.09; P=0.2629), as was median OS,
      23.6 vs 25.6 months (HR, 0.93; 95% CI: 0.74-1.18; P=0.5442). Similarly, in
      cytokine-refractory patients, median PFS was 8.1 vs 8.4 months (HR, 0.79; 95% CI:
      0.49-1.28; P=0.3350), while median OS was 20.2 vs 15.8 months (HR, 1.14; 95% CI:
      0.73-1.79; P=0.5657). Some treatment-emergent adverse events were significantly
      less common in younger vs older patients, including fatigue (60% vs 69%), cough
      (20% vs 29%), peripheral edema (17% vs 27%), anemia (18% vs 25%), decreased
      appetite (13% vs 29%), and thrombocytopenia (16% vs 25%; all P<0.05). Hand-foot
      syndrome was more common in younger patients (32% vs 24%). CONCLUSIONS: Advanced
      age should not be a deterrent to sunitinib therapy and elderly patients may
      achieve additional clinical benefit.

PMID- 24434435
TI  - TMPRSS4 regulates levels of integrin alpha5 in NSCLC through miR-205 activity to
      promote metastasis.
AB  - BACKGROUND: TMPRSS4 is a membrane-anchored protease involved in cell migration
      and invasion in different cancer types including lung cancer. TMPRSS4 expression
      is increased in NSCLC and its inhibition through shRNA reduces lung metastasis.
      However, molecular mechanisms leading to the protumorigenic regulation of TMPRSS4
      in lung cancer are unknown. METHODS: miR-205 was identified as an overexpressed
      gene upon TMPRSS4 downregulation through microarray analysis. Cell migration and
      invasion assays and in vivo lung primary tumour and metastasis models were used
      for functional analysis of miR-205 overexpression in H2170 and H441 cell lines.
      Luciferase assays were used to identify a new miR-205 direct target in NSCLC.
      RESULTS: miR-205 overexpression promoted an epithelial phenotype with increased E
      cadherin and reduced fibronectin. Furthermore, miR-205 expression caused a G0/G1
      cell cycle arrest and inhibition of cell growth, migration, attachment to
      fibronectin, primary tumour growth and metastasis formation in vivo. Integrin
      alpha5 (a proinvasive protein) was identified as a new miR-205 direct target in
      NSCLC. Integrin alpha5 downregulation in lung cancer cells resulted in complete
      abrogation of cell migration, a decreased capacity to adhere to fibronectin and
      reduced in vivo tumour growth, compared with control cells. TMPRSS4 silencing
      resulted in a concomitant reduction of integrin alpha5 levels. CONCLUSION: We
      have demonstrated for the first time a new molecular pathway that connects
      TMPRSS4 and integrin alpha5 through miR-205 to regulate cancer cell invasion and
      metastasis. Our results will help designing new therapeutic strategies to inhibit
      this novel pathway in NSCLC.

PMID- 24434436
TI  - Role of SNTA1 in Rac1 activation, modulation of ROS generation, and migratory
      potential of human breast cancer cells.
AB  - BACKGROUND: Alpha-1-syntrophin (SNTA1) has been implicated in the activation of
      Rac1. However, the underlying mechanism has not yet been explored. Here, we show
      that a novel complex, involving SNTA1, P66shc, and Grb2 proteins, is involved in
      Rac1 activation. METHODS: Co-immunoprecipitation assays were used to show the
      complex formation, while siRNAs and shRNAs were used to downregulate expression
      of these proteins. Various Rac1 activation assays and functional assays, such as
      migration assays, in vitro wound healing assays, cell proliferation assays, and
      ROS generation assays, were also performed. RESULTS: The results showed a
      significant increase in activation of Rac1 when SNTA1 and P66shc were
      overexpressed, whereas depletion of SNTA1 and P66shc expression effectively
      reduced the levels of active Rac1. The results indicated a significant
      displacement of Sos1 protein from Grb2 when SNTA1 and P66shc are overexpressed in
      breast cancer cell lines, resulting in Sos1 predominantly forming a complex with
      Eps8 and E3b1. In addition, the SNTA1/P66shc-mediated Rac1 activation resulted in
      an increase in reactive oxygen species (ROS) production and migratory potential
      in human breast cancer cells. CONCLUSION: Together, our results present a
      possible mechanism of Rac1 activation involving SNTA1 and emphasise its role in
      ROS generation, cell migration, and acquisition of malignancy.

PMID- 24434437
TI  - Hypothyroidism affects D2 receptor-mediated breathing without altering D2
      receptor expression.
AB  - Bromocriptine depressed ventilation in air and D2 receptor expression in the
      nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated
      that in age-matched hypothyroid female hamsters, the pattern of D2 receptor
      modulation of breathing and D2 receptor expression would differ from those
      reported in hypothyroid males. In females hypothyroidism did not affect D2
      receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine,
      but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen
      consumption and body temperature in awake air-exposed hypothyroid female hamsters
      and stimulated their ventilation before and following exposure to hypoxia.
      Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to,
      during and following hypoxia exposures and stimulated it in the hypothyroid
      hamsters following hypoxia. Although hypothyroidism did not affect expression of
      D2 receptors, it influenced central D2 modulation of breathing in a disparate
      manner relative to euthyroid hamsters. 

PMID- 24434439
TI  - Effect of intensive atorvastatin therapy on periprocedural PDCD4 expression in
      CD4+ T lymphocytes of patients with unstable angina undergoing percutaneous
      coronary intervention.
AB  - OBJECTIVE: To investigate the effects of intensive atorvastatin therapy on
      programmed cell death 4 (PDCD4) expression by CD4+ T lymphocytes in patients with
      unstable angina who received percutaneous coronary intervention (PCI). METHODS:
      Patients with unstable angina were randomized to pretreatment with either an
      intensive dose (80 mg/day, n = 33) or a conventional dose (20 mg/day, n = 33) of
      atorvastatin. Circulating CD4+ T cells were subsequently obtained prior to PCI,
      and also 18-24 h after PCI, using a magnetic cell sorting system. Fluorescence
      based quantitative real-time PCR was then used to measure levels of PDCD4 mRNA in
      the isolated CD4+ T lymphocytes, and Western blot analysis was used to detect
      levels of PDCD4. Serum levels of interleukin (IL)-10 and TNF-alpha were
      quantified using enzyme-linked immunosorbent assays. RESULTS: Of the 66 patients
      with unstable angina that were examined, levels of PDCD4 mRNA and protein were
      found to dramatically decrease in patients who received an intensive dose of
      atorvastatin following PCI (p < 0.05). In contrast, serum levels of TNF-alpha
      significantly increased following PCI in both the intensive dose group and the
      conventional dose group, with the latter being higher than the former (p < 0.05).
      Serum IL-10 levels also markedly increased following PCI for the two groups.
      However, higher values were associated with the intensive dose group (p < 0.05).
      CONCLUSIONS: Intensive atorvastatin treatment reduced the post-PCI myocardial
      inflammatory response in patients with unstable angina, possibly by inhibiting
      PDCD4 expression in CD4+ T lymphocytes.

PMID- 24434440
TI  - Investigating conflict in ICUs-is the clinicians' perspective enough?
AB  - OBJECTIVE: Most studies have assessed conflict between clinicians and surrogate
      decision makers in ICUs from only clinicians' perspectives. It is unknown if
      surrogates' perceptions differ from clinicians'. We sought to determine the
      degree of agreement between physicians and surrogates about conflict and to
      identify predictors of physician-surrogate conflict. DESIGN: Prospective cohort
      study. SETTING: Four ICUs of two hospitals in San Francisco, California.
      PATIENTS: Two hundred and thirty surrogate decision makers and 100 physicians of
      175 critically ill patients. MEASUREMENTS: Questionnaires addressing
      participants' perceptions of whether there was physician-surrogate conflict, as
      well as attitudes and preferences about clinician-surrogate communication; kappa
      scores to quantify physician-surrogate concordance about the presence of
      conflict; and hierarchical multivariate modeling to determine predictors of
      conflict. MAIN RESULTS: Either the physician or surrogate identified conflict in
      63% of cases. Physicians were less likely to perceive conflict than surrogates
      (27.8% vs 42.3%; p = 0.007). Agreement between physicians and surrogates about
      conflict was poor (kappa = 0.14). Multivariable analysis with surrogate-assessed
      conflict as the outcome revealed that higher levels of surrogates' satisfaction
      with physicians' bedside manner were associated with lower odds of conflict (odds
      ratio, 0.75 per 1 point increase in satisfaction; 95% CI, 0.59-0.96).
      Multivariable analysis with physician-assessed conflict as the outcome revealed
      that the surrogate having felt discriminated against in the healthcare setting
      was associated with higher odds of conflict (odds ratio, 17.5; 95% CI, 1.6-190.1)
      while surrogates' satisfaction with physicians' bedside manner was associated
      with lower odds of conflict (0-10 scale; odds ratio, 0.76 per 1 point increase;
      95% CI, 0.58-0.99). CONCLUSIONS: Conflict between physicians and surrogates is
      common in ICUs. There is little agreement between physicians and surrogates about
      whether physician-surrogate conflict has occurred. Further work is needed to
      develop reliable and valid methods to assess conflict. In the interim, future
      studies should assess conflict from the perspective of both clinicians and
      surrogates.

PMID- 24434441
TI  - Therapeutic hypothermia is cool, but be aware of the infection heat*.

PMID- 24434442
TI  - Training pediatric rapid response teams: the next layer?

PMID- 24434443
TI  - Positive end-expiratory pressure in acute respiratory distress syndrome: when
      should we turn up the pressure?

PMID- 24434444
TI  - Tapping a vital resource: increasing the yield of family care conferences.

PMID- 24434445
TI  - Studying community consultation in exception from informed consent trials.

PMID- 24434446
TI  - Outcomes in elderly patients resuscitated from cardiac arrest: is age an
      independent predictor?

PMID- 24434447
TI  - Clinical and economic implications of timing of limitations in life support.

PMID- 24434449
TI  - Rapid response systems call: an indication for a palliative care assessment?

PMID- 24434448
TI  - Adjuvant immunosuppression in the management of severe influenza: friend or foe?

PMID- 24434450
TI  - The epidemic of physician-family conflict in the ICU and what we should do about
      it.

PMID- 24434451
TI  - The effect of organizational structure and processes of care on ICU mortality as
      revealed by the United States critical illness and injury trials group critical
      illness outcomes study.

PMID- 24434452
TI  - Defining an Intermediate Step in End-of-Life Therapy.

PMID- 24434453
TI  - Duration of delirium and postintensive care functional outcome: over the hill?

PMID- 24434454
TI  - Intra-abdominal pressure: why are you not measuring it?

PMID- 24434455
TI  - Toxicity with hyperoxia in brain injury? Retrospection identifies unforeseen
      obstacles.

PMID- 24434456
TI  - Working toward "just right": fluid balance in pediatric septic shock.

PMID- 24434457
TI  - Inhaled nitric oxide in patients with acute respiratory distress syndrome: an end
      to the debate?

PMID- 24434458
TI  - Use of inhaled anticoagulants for treatment of smoke inhalation-associated acute
      lung injury-playing the waiting game.

PMID- 24434459
TI  - Macrolides and mortality in severe community-acquired pneumonia.

PMID- 24434460
TI  - Prevention and treatment of methicillin-resistant Staphylococcus aureus
      colonization in the ICU: a process of care that should be considered mandatory.

PMID- 24434461
TI  - Intermittent positive-pressure ventilation, chest compression synchronized
      ventilation, bilevel ventilation, continuous chest compression, active
      compression decompression, and impedance threshold device-the complexity of
      ventilation during cardiopulmonary resuscitation.

PMID- 24434462
TI  - The right target at the right time: the microcirculation in circulatory shock.

PMID- 24434463
TI  - In comatose postcardiac arrest patients treated with therapeutic hypothermia:
      what is the optimal rate of rewarming?

PMID- 24434464
TI  - Brain perfusion in sepsis or to resolve the macro part of the micro.

PMID- 24434465
TI  - Targeting toll-like receptors 4 intracellular domain to prevent ischemic liver
      disease: an innovative approach or just a futuristic dream?.

PMID- 24434466
TI  - If some hypothermia is good, more hypothermia must be better, right?

PMID- 24434467
TI  - The remarkable career of leptin: from antidote to obesity to mediator of lung
      inflammation.

PMID- 24434468
TI  - Preventing ventilator-induced diaphragmatic dysfunction with phrenic nerve
      stimulation.

PMID- 24434469
TI  - Volatile anesthetic sedation during therapeutic hypothermia after cardiac arrest
      in the ICU: a journey of a thousand miles begins with a single step.

PMID- 24434470
TI  - The effects of the rate of postresuscitation rewarming following hypothermia on
      outcomes of cardiopulmonary resuscitation in a rat model.
AB  - OBJECTIVE: To investigate the optimal rewarming rate following therapeutic
      hypothermia in a rate model of cardiopulmonary resuscitation. Both clinical and
      laboratory studies have demonstrated that mild therapeutic hypothermia following
      cardiopulmonary resuscitation improves myocardial and neurologic outcomes of
      cardiac arrest. However, the optimal rewarming strategy following therapeutic
      hypothermia remains to be explored. DESIGN: Prospective randomized controlled
      experimental study. SETTING: University-affiliated research institution.
      SUBJECTS: Twenty-three healthy male Sprague-Dawley rats. INTERVENTIONS: Four
      groups of Sprague-Dawley rats were randomized: 1) normothermia group (control),
      2) rewarming rate at 2 degrees C/hr, 3) rewarming rate at 1 degrees C/hr, and 4)
      rewarming rate at 0.5 degrees C/hr. Ventricular fibrillation was induced and
      untreated for 8 minutes, and defibrillation was attempted after 8 minutes of
      cardiopulmonary resuscitation. For the 2, 1, and 0.5 degrees C/hr groups, rapid
      cooling was started at the beginning of cardiopulmonary resuscitation. On
      reaching the target cooling temperature of 33 degrees C +/- 0.2 degrees C, the
      temperature was maintained with the aid of a cooling blanket until 4 hours after
      resuscitation. Rewarming was then initiated at the rate of 2.0, 1.0, or 0.5
      degrees C/hr, respectively, until the body temperature reached 37 degrees C +/
      0.2 degrees C. Blood samples were drawn at baseline and postresuscitation of 4,
      6, 8, 10, and 12 hours for the measurements of blood gas and serum biomarkers.
      MEASUREMENTS AND MAIN RESULTS: Blood temperature significantly decreased in the
      hypothermic groups from cardiopulmonary resuscitation to postresuscitation 4
      hours. Significantly better cardiac output, ejection fraction, myocardial
      performance index, reduced neurologic deficit scores, and longer duration of
      survival were observed in the 1 and 0.5 degrees C/hr groups. The increased serum
      concentration of troponin I, interleukin-6, and tumor necrosis factor-alpha was
      partly attenuated in the 1 and 0.5 degrees C/hr groups when compared with the
      control and 2 degrees C/hr groups. CONCLUSIONS: This study demonstrated that the
      severity of myocardial, cerebral injuries, and inflammatory reaction after
      cardiopulmonary resuscitation was reduced when mild therapeutic hypothermia was
      applied. A rewarming rate at 0.5-1 degrees C/hr did not alter the beneficial
      effects of therapeutic hypothermia. However, a rapid rewarming rate at 2 degrees
      C/hr abolished the beneficial effects of hypothermia.

PMID- 24434471
TI  - Possible negative impact of bundle care for preventing central catheter-related
      infection.

PMID- 24434472
TI  - The authors reply.

PMID- 24434473
TI  - Trials of biomarker-guided antimicrobial therapy in sepsis: improvements in trial
      design require better control groups.

PMID- 24434474
TI  - The authors reply.

PMID- 24434475
TI  - Mistaking complications of critical illness for those of critical care.

PMID- 24434476
TI  - The authors reply.

PMID- 24434477
TI  - Sex differences in behavioral outcome following neonatal hypoxia ischemia:
      insights from a clinical meta-analysis and a rodent model of induced hypoxic
      ischemic brain injury.
AB  - Hypoxia ischemia (HI; reduced oxygen and/or blood flow to the brain) is one of
      the most common injuries among preterm infants and term infants with birth
      complications. Both populations show cognitive/behavioral deficits, including
      impairments in sensory, learning/memory, and attention domains. Clinical data
      suggests a sex difference in HI outcomes, with males exhibiting more severe
      cognitive/behavioral deficits relative to matched females. Our laboratory has
      also reported more severe behavioral deficits among male rats with induced HI
      relative to females with comparable injury (Hill et al., 2011a,b). The current
      study initially examined published clinical studies from the past 20years where
      long-term IQ outcome scores for matched groups of male and female premature
      infants were reported separately (IQ being the most common outcome measure). A
      meta-analysis revealed a female "advantage," as indicated by significantly better
      scores on performance and full scale IQ (but not verbal IQ) for premature
      females. We then utilized a rodent model of neonatal HI injury to assess sham and
      postnatal day 7 (P7) HI male and female rats on a battery of behavioral tasks.
      Results showed expected deficits in HI male rats, but also showed task-dependent
      sex differences, with HI males having significantly larger deficits than HI
      females on some tasks but equivalent deficits on other tasks. In contrast to
      behavioral results, post mortem neuropathology associated with HI was comparable
      across sex. These findings suggest: 1) neonatal female "protection" in some
      behavioral domains, as indexed by superior outcome following early injury
      relative to males; and 2) female protection may entail sex-specific plasticity or
      compensation, rather than a reduction in gross neuropathology. Further
      exploration of the mechanisms underlying this sex effect could aid in
      neuroprotection efforts for at-risk neonates in general, and males in particular.
      Moreover, our current report of comparable anatomical damage coupled with
      differences in cognitive outcomes (by sex) provides a framework for future
      studies to examine neural mechanisms underlying sex differences in cognition and
      behavior in general. 

PMID- 24434478
TI  - Treatment of hepatitis C with an interferon-based lead-in phase: a perspective
      from mathematical modelling.
AB  - BACKGROUND: The standard of care for HCV genotype 1 is a protease inhibitor
      (telaprevir or boceprevir) combined with pegylated interferon (PEG-IFN) and
      ribavirin (RBV). A lead-in phase of PEG-IFN/RBV therapy before addition of the
      protease inhibitor has been used, with the aim of improving response rates by
      reducing the development of protease inhibitor resistance. However, whether such
      a strategy can bring benefit to patients is unclear. METHODS: A viral dynamic
      model was used to compare in silico HCV dynamics in patients treated with a
      period of PEG-IFN/RBV lead-in therapy followed by the addition of a protease
      inhibitor versus immediate triple therapy without lead-in. RESULTS: The model
      predicts that both regimens result in a similar end-of-treatment viral load
      change (viral decline or breakthrough). Thus, the current lead-in strategy may
      not decrease the rate of viral breakthrough/relapse or increase the rate of
      sustained virological response. This agrees with available data from clinical
      trials of several HCV protease inhibitors, such as telaprevir, boceprevir and
      faldaprevir. CONCLUSIONS: These results suggest that current PEG-IFN/RBV lead-in
      strategies may not improve treatment outcomes. However, viral kinetics during a
      period of PEG-IFN/RBV therapy, combined with other factors, such as the IL28B
      polymorphism and baseline viral load, can identify IFN-sensitive patients and
      help develop response-guided therapies.

PMID- 24434479
TI  - Older adult experience of online diagnosis: results from a scenario-based think
      aloud protocol.
AB  - BACKGROUND: Searching for online information to interpret symptoms is an
      increasingly prevalent activity among patients, even among older adults. As older
      adults typically have complex health care needs, their risk of misinterpreting
      symptoms via online self-diagnosis may be greater. However, limited research has
      been conducted with older adults in the areas of symptom interpretation and human
      computer interaction. OBJECTIVE: The intent of the study was to describe the
      processes that a sample of older adults may use to diagnose symptoms online as
      well as the processes that predict accurate diagnosis. METHODS: We conducted a
      series of "think-aloud" protocols with 79 adults aged 50 years or older.
      Participants received one of two vignettes that depicted symptoms of illness.
      Participants talked out loud about their thoughts and actions while attempting to
      diagnose the symptoms with and without the help of common Internet tools (Google
      and WebMD's Symptom Checker). Think-aloud content was categorized using an
      adapted Q-sort and general inductive approach. We then compared the think-aloud
      content of participants who were accurate in their diagnosis with those who were
      not. RESULTS: Nineteen descriptive codes were identified from the think-aloud
      content. The codes touched upon Web navigation, attempts to organize and evaluate
      online health information, and strategies to diagnose symptoms. Participants most
      frequently relied on a strategy where they reviewed and then rejected the online
      diagnoses if they contained additional symptoms than those that were depicted in
      the vignette. Finally, participants who were inaccurate in their diagnosis
      reported being confused by the diagnosis task, lacking confidence in their
      diagnosis, and using their past experiences with illness to guide diagnosis more
      frequently than those participants who accurately diagnosed the symptoms.
      CONCLUSIONS: Older adult participants tended to rely on matching strategies to
      interpret symptoms, but many still utilized existing medical knowledge and
      previous illness experiences as a guide for diagnosis. Many participants also had
      difficulty navigating the Internet tools, which suggests an increased need for
      navigation aids in Web design. Furthermore, participants who were inaccurate in
      their diagnosis had more difficulty with the Internet tools and confusion with
      the task than those who were accurate. Future work in this area may want to
      utilize additional study design such as eye-tracking to further understand the
      coordination between Web navigation, online symptom information processing, and
      diagnostic strategies.

PMID- 24434482
TI  - DCD pigs' kidneys analyzed by MRI to assess ex vivo their viability.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) gadolinium-perfusion was applied in
      simulated Donation after Cardiac Death (DCD) in porcine kidneys to measure
      intrarenal perfusion. Adenosine triphosphate (ATP) resynthesis during oxygenated
      hypothermic perfusion was compared to evaluate the "ex vivo organ viability".
      Adenine nucleotide (AN) was measured by P nuclear magnetic resonance (NMR)
      spectroscopy. Whereas this latter technique requires sophisticated hardware,
      gadolinium-perfusion can be realized using any standard proton-MRI scanner. The
      aim of this work was to establish a correlation between the two methods. METHODS:
      Twenty-two porcine kidneys presenting up to 90 min warm ischemia were perfused
      with oxygenation at 4  degrees C using our magnetic resonance-compatible machine.
      During the perfusion, P NMR spectroscopy and gadolinium-perfusion sequences were
      performed. Measures obtained from the gadolinium-perfusion were the speed of
      elimination of the cortical gadolinium and the presence or absence of a
      corticomedullar shunt. For ATP resynthesis analysis, P chemical shift imaging was
      acquired and analyzed. All the kidneys have been submitted to histologic
      examination. RESULTS: ATP resynthesis was observed in all organs presenting a
      cortical gadolinium elimination slope of (-) 23 degrees  or greater. In organs
      with lower gadolinium elimination, no AN or only precursors were detected. This
      study reveals a link between the two methods and demonstrates ex vivo viability
      in 93% of the analyzed kidneys. Benefits and side effects of both methods are
      discussed. CONCLUSION: Oxygenated hypothermic perfusion enables the evaluation of
      kidneys in DCD simulated situation; gadolinium-perfusion can be introduced into
      any center equipped with a proton-MRI scanner allowing results superposable with
      ATP measurement.

PMID- 24434483
TI  - Targeting platelet migration in the postischemic liver by blocking protease
      activated receptor 4.
AB  - BACKGROUND: Platelets play a critical role during hepatic ischemia/reperfusion
      (I/R). Antiplatelet strategies during liver transplantation are, however, limited
      because of bleeding complications. Thrombin is activated during reperfusion and
      regulates platelet and endothelial cell function via protease-activated receptor
      4 (PAR-4). Interventions at the level of PAR-4, the main platelet receptor for
      thrombin, are assumed to attenuate the proinflammatory effects of thrombin
      without affecting blood coagulation. The aim of our study was to analyze the
      impact of PAR-4 blockade on platelet recruitment and microvascular injury during
      hepatic I/R. METHODS: C57BL/6 mice undergoing hepatic I/R (90 min/60 min and 240
      min) were treated either with a selective PAR-4 antagonist TcY-NH2 or vehicle.
      Sham-operated animals served as controls. Recruitment of freshly isolated and
      fluorescence-labeled platelets and CD4 T cells was analyzed using intravital
      video fluorescence microscopy. Parameters of tissue injury, regeneration, and
      blood coagulation were assessed in tissue/blood samples. RESULTS: Results show
      that treatment with TcY-NH2 attenuated I/R-induced platelet and CD4 T-cell
      recruitment, improved sinusoidal perfusion failure, and reduced apoptotic and
      necrotic injury. The protective effect of PAR-4 blockade did not suppress
      hemostasis or liver regeneration. CONCLUSION: Our in vivo data suggest PAR-4 as a
      potential target for future therapeutic strategies against platelet-mediated
      liver injury on transplantation.

PMID- 24434484
TI  - Intestinal mucormycosis with Rhizopus microsporus after liver transplantation-
      successful treatment of a rare but life-threatening complication.

PMID- 24434485
TI  - The successful use of telaprevir to treat hepatitis C recurrence after liver
      transplantation in an HIV co-infected patient.

PMID- 24434486
TI  - Wait and transplant for stage 2 hepatocellular carcinoma with deceased-donor
      liver grafts: how long should we wait?

PMID- 24434487
TI  - Reply to "Wait and transplant for stage 2 hepatocellular carcinoma with deceased
      donor liver grafts: how long should we wait?".

PMID- 24434488
TI  - ABO-incompatible paired kidney exchange for failed desensitization.

PMID- 24434489
TI  - The incretin response after successful islet transplantation.

PMID- 24434490
TI  - Cutaneous reactions in patients with chronic hepatitis C treated with
      peginterferon and ribavirin.
AB  - BACKGROUND/OBJECTIVE: Peginterferon alfa and ribavirin could cause various
      cutaneous reactions. Treatment-related cutaneous reactions are common, and
      treatable complications can contribute to the treatment discontinuation. METHODS:
      We performed a 6-year prospective study of cutaneous reactions in 271 patients
      with chronic hepatitis C treated with peginterferon and ribavirin. RESULTS:
      Cutaneous reactions of mild to moderate degree were seen in 36 (13.3%) patients:
      localized cutaneous reactions in 7 (2.6%) patients, generalized reactions -
      pruritus, skin xerosis and eczematous changes - in 28 (10.3%) patients, alopecia
      in 11 (4.1%) patients; exacerbation of lichen planus was seen in 1 patient.
      CONCLUSION: The study showed a relatively low prevalence of cutaneous reactions
      without the need for discontinuation of any of the drugs used. These reactions
      correlated only with the age of the patients and treatment duration. This finding
      is of particular importance with regard to the recently introduced direct-acting
      antivirals in the treatment of hepatitis C virus infection, which can cause a
      very severe form of cutaneous reactions.

PMID- 24434491
TI  - Quality assurance for high dose rate brachytherapy treatment planning
      optimization: using a simple optimization to verify a complex optimization.
AB  - As dose optimization for high dose rate brachytherapy becomes more complex, it
      becomes increasingly important to have a means of verifying that optimization
      results are reasonable. A method is presented for using a simple optimization as
      quality assurance for the more complex optimization algorithms typically found in
      commercial brachytherapy treatment planning systems. Quality assurance tests may
      be performed during commissioning, at regular intervals, and/or on a patient
      specific basis. A simple optimization method is provided that optimizes conformal
      target coverage using an exact, variance-based, algebraic approach. Metrics such
      as dose volume histogram, conformality index, and total reference air kerma agree
      closely between simple and complex optimizations for breast, cervix, prostate,
      and planar applicators. The simple optimization is shown to be a sensitive
      measure for identifying failures in a commercial treatment planning system that
      are possibly due to operator error or weaknesses in planning system optimization
      algorithms. Results from the simple optimization are surprisingly similar to the
      results from a more complex, commercial optimization for several clinical
      applications. This suggests that there are only modest gains to be made from
      making brachytherapy optimization more complex. The improvements expected from
      sophisticated linear optimizations, such as PARETO methods, will largely be in
      making systems more user friendly and efficient, rather than in finding
      dramatically better source strength distributions. 

PMID- 24434492
TI  - Novel plasmonic field-enhanced nanoassay for trace detection of proteins.
AB  - Recently discovered effects of plasmonic field on molecular fluorescence offer
      new insights into the optical interactions at the nanoscale which can help
      solving problems encountered in widely applied fluorescent labeling of
      biomolecules for studying life processes in biomedicine and pharmacy. In this
      work, we have focused on exploring a novel sensitivity-enhancing phenomenon based
      on protein modulation of plasmon-controlled fluorescence. We have demonstrated
      that a protein (cytochrome c (Cytc c) or bovine serum albumin (BSA)) can be
      employed to gate fluorescence resonance energy transfer occurring from a
      fluorescein isothiocyanate fluorescent dye to plasmonic citrate-capped gold
      nanoparticles. By applying plasmonic field gated by protein, facilitated by the
      formation of multi-shell nanoparticles, (AuNP@Cit/Cytc-FITC or AuNP@Cit/BSA
      FITC), low limits of detection for Cyt c (LOD = 370 pM) and for BSA (LOD = 1.8
      nM) have been achieved even for large fluorophore:protein ratios, up to 30:1
      (over-labeling), normally plagued with energy migration and background
      fluorescence problems. Control experiments confirming adsorption of proteins on
      AuNPs have been performed using light scattering and piezometric techniques. The
      proposed nanoassay may be applied in microanalysis of trace amounts of proteins,
      e.g. in microfluidic devices.

PMID- 24434493
TI  - Novel pyrazoline-based fluorescent probe for detecting glutathione and its
      application in cells.
AB  - A novel compound, 2-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl acrylate
      (probe L), was designed and synthesized as a highly sensitive and selective
      fluorescent probe for recognizing and detecting glutathione among cysteine,
      homocysteine and other amino acids. The structures of related compounds were
      characterized using IR, NMR and HRMS spectroscopy analysis. The probe is a non
      fluorescent compound. On being mixed with glutathione in buffered EtOH:PBS=3:7
      solution at pH 7.4, the probe exhibited the blue emission of the pyrazoline at
      474 nm and a 83-fold enhancement in fluorescence intensity. This probe is very
      sensitive and displayed a linear fluorescence off-on response to glutathione with
      fluorometric detection limit of 8.2 * 10(-8)M. The emission of the probe is pH
      independent in the physiological pH range. Live-cell imaging of HeLa cells
      confirmed the cell permeability of the probe and its ability to selectively
      discriminate GSH from Cys and Hcy in cells. The toxicity of the probe was low in
      cultured HeLa cells.

PMID- 24434494
TI  - Development of colloidal gold-based immunochromatographic assay for rapid
      detection of Mycoplasma suis in porcine plasma.
AB  - A one-step immunochromatographic assay using gold nanoparticles coated with
      polyclonal antibody (pAb) against Mycoplasma suis (M. suis) was developed in this
      study for the detection of M. suis in porcine plasma. The colloidal gold was
      prepared by the reduction of gold salt with sodium citrate coupled with pAb
      against M. suis. The pAb was produced by immunizing the BALB/c mice with
      recombinant MSG1 (rMSG1) protein from M. suis expressed in Escherichia coli. The
      optimal concentrations of the capture antibody and the coating antibody were 12
      MUg/ml and 1.5 mg/ml, respectively, and that of the blocking buffer was 1% bovine
      serum albumin. The lower detection limit of the immunochromatographic assay test
      was 100 ng/ml with visual detection under optimal conditions of analysis.
      Classical swine fever virus, porcine reproductive and respiratory syndrome virus,
      swine pneumonia mycoplasma, swine toxoplasma, and porcine parvovirus were used to
      evaluate the specificity of the immunochromatographic strips. No cross-reaction
      of the antibodies with other related swine pathogens was observed. This
      qualitative test based on the visual evaluation of the results did not require
      any equipment. The assay time for M. suis detection was less than 10 min,
      suitable for rapid detection at the grassroots level. The one-step colloidal gold
      immunochromatographic strips that we developed had high specificity and
      sensitivity. Therefore, this method would be feasible, convenient, rapid, and
      effective for detecting M. suis in porcine plasma.

PMID- 24434495
TI  - Nicking enzyme-assisted biosensor for Salmonella enteritidis detection based on
      fluorescence resonance energy transfer.
AB  - Salmonella enteritidis (S. enteritidis) outbreaks continue to occur, and have
      increased public awareness of this pathogen. Nicking endonuclease Nb.BbvC I is
      widely used for the detection of biomolecules and displays activity for specific
      double-stranded DNA (dsDNA). In this study, we developed a biosensor to detect S.
      enteritidis based on fluorescence resonance energy transfer (FRET) using nicking
      enzyme and carbon nanoparticles (CNPs). Because of the quenching effect of black
      hole quencher 1 (BHQ 1), the CNPs do not fluoresce in the reaction system. When
      the target bacteria are added, the nicking enzyme recognizes and cleaves the
      dsDNA fabricated by the interaction between probe and target. As a result, the
      CNPs dissociate from BHQ 1 and emit strong fluorescence. Using the nicking
      enzyme, the fluorescence signals of the biosensor are greatly amplified. The
      biosensor exhibited a linear relationship with the concentration of S.
      enteritidis ranging from 10(2) to 3 * 10(3)CFU/mL in water and from 1.5 * 10(2)
      to 3 * 10(3)CFU/mL in milk. The present results indicate that our FRET-based
      detection system can be widely employed for the effective detection of pathogens.

PMID- 24434496
TI  - Highly sensitive and quantitative human thrombospondin-1 detection by an M55
      aptasensor and clinical validation in patients with atherosclerotic disease.
AB  - Aptamer-based biosensors (aptasensor) are powerful tools for rapid and sensitive
      biomarker detection. In this study, we report a DNA aptamer probe evolved from
      cell-SELEX that can recognize thrombospondin-1 protein in human plasma samples.
      The KD value of the aptamer M55 binding to thrombospondin-1 was determined as 0.5
      +/- 0.2 MUM with an R(2) of 0.9144. A horseradish peroxidase-linked short oligo
      was complementarily bound onto the 3' end of the aptamer sequence to facilitate
      the 'smart' design of an M55-aptasensor for quantifying thrombospondin-1 protein
      in plasma samples. The limit of detection was 6.96 fM. Thrombospondin-1 is a
      glycoprotein with multiple biological functions, including inflammation, platelet
      aggregation and endothelial cell apoptosis, and is involved in the pathology of
      atherosclerosis. In total, 118 plasma subjects were analyzed by using the
      aptasensor measurement with 1 MUL sample volume and 5 min incubation time. The
      thrombospondin-1 concentrations in ST-Elevation Myocardial Infarction patients
      with severe atherosclerotic plaque burden were statistically significantly higher
      than in the healthy volunteers without atherosclerosis conditions, suggesting
      that thromboposnidn-1 is a potential plasma biomarker for atherosclerosis
      progression.

PMID- 24434497
TI  - Aptamer-based portable biosensor for platelet-derived growth factor-BB (PDGF-BB)
      with personal glucose meter readout.
AB  - A novel portable biosensor for sensitive and selective detection of platelet
      derived growth factor-BB (PDGF-BB) had been developed based on the specific
      recognition between aptamer and protein using a personal glucose meter (PGM) as
      readout. In the presence of PDGF-BB, the primary aptamer of PDGF-BB which is
      bound to the surface of streptavidin magnespheres paramagnetic particles (SA
      PMPs) reacts quantitatively with invertase-functionalized secondary aptamer of
      PDGF-BB to form a stable complex, resulting in the attachment of invertase on the
      SA-PMPs. Subsequently, the invertase catalyzes the hydrolysis of sucrose to
      produce a large amount of glucose and quantitative readout by the PGM. The
      enhanced signal of the PGM has a relationship with the concentration of PDGF-BB
      in the range of 1.0 * 10(-14) M~3.16 * 10(-12) M, and the detection limit is 2.9
      fM. The proposed portable biosensor had been successfully applied to assay the
      PDGF-BB in saliva samples.

PMID- 24434498
TI  - Nano-yeast-scFv probes on screen-printed gold electrodes for detection of
      Entamoeba histolytica antigens in a biological matrix.
AB  - The time and costs associated with monoclonal antibody production limit the
      potential for portable diagnostic devices to penetrate the market. Replacing the
      antibody with a low-cost alternate affinity reagent would reduce the costs of
      diagnostic development and use, and lead to new portable diagnostic devices
      towards many diseases. Herein, we present low-cost affinity reagents, nano-yeast
      scFv, on commercially available, inexpensive, and portable screen-printed
      electrodes for the label-free electrochemical detection of Entamoeba histolytica
      cyst antigens. The biosensor was able to detect antigen at concentrations down to
      10 pg mL(-1) in buffer with an inter-assay reproducibility of (% RSD, n=3) 4.1%.
      The applicability of two differently engineered nano-yeast-scFv to each
      specifically detect their cognant E. histolytica cyst antigens was demonstrated
      in a biological matrix derived from human stool. Because of the simple,
      inexpensive, and sensitive nature of this methodology, it may offer a low-cost
      alternative to immunosensors based on antibody-target recognition.

PMID- 24434499
TI  - A recombinant estrogen receptor fragment-based homogeneous fluorescent assay for
      rapid detection of estrogens.
AB  - In this work, we demonstrate a novel estrogenic receptor fragment-based
      homogeneous fluorescent assay which enables rapid and sensitive detection of
      17beta-estradiol (E2) and other highly potent estrogens. A modified human
      estrogenic receptor fragment (N-His * 6-hER270-595-C-Strep tag II) has been
      constructed that contains amino acids 270-595 of wild-type human estrogenic
      receptor alpha (hER270-595) and two specific tags (6 * His and Strep tag II)
      fused to the N and C terminus, respectively. The designed receptor protein
      fragment could be easily produced by prokaryotic expression with high yield and
      high purity. The obtained protein exhibits high binding affinity to E2 and the
      two tags greatly facilitate the application of the recombinant protein. Taking
      advantage of the unique spectroscopic properties of coumestrol (CS), a
      fluorescent phytoestrogen, a CS/hER270-595-based fluorescent assay has been
      developed which can sensitively respond to E2 within 1.0 min with a linear
      working range from 0.1 to 20 ng/mL and a limit of detection of 0.1 ng/mL. The
      assay was successfully applied for rapid detection of E2 in the culture medium of
      rat hippocampal neurons. The method also holds great potential for high
      throughput monitoring the variation of estrogen levels in complex biological
      fluids, which is crucial for investigation of the molecular basis of various
      estrogen-involved processes.

PMID- 24434500
TI  - Liver tuberculosis presenting as an uncommon cause of pyrexia of unknown origin:
      positron emission tomography/computed tomography identifies the correct site for
      biopsy.
AB  - OBJECTIVE: To identify the correct site to biopsy in a case of pyrexia of unknown
      origin (PUO) caused by hepatic tuberculosis (TB). CLINICAL PRESENTATION AND
      INTERVENTION: A 58-year-old man who developed hepatic TB presented with PUO.
      Ultrasonography (US) and computed tomography (CT) of the abdomen showed only
      calcifications in the liver, and positron emission tomography (PET)/CT showed
      diffuse increased metabolic activity in addition to focal areas of increased
      activity. A diagnosis of hepatic TB was confirmed by histological examination of
      liver tissues and interferon-gamma release assays (IGRAs of T-SPOT/TB). The
      patient was treated with 4 anti-tubercular therapies (rifampicin, isoniazid,
      ethambutol and pyrazinamide). At the 3-month follow-up, the patient was disease
      free as confirmed by abdominal US. CONCLUSION: PET/CT was helpful in identifying
      a site to biopsy that led to the correct diagnosis.

PMID- 24434501
TI  - PSC: Novel disease associations providing pathogenetic clues?

PMID- 24434502
TI  - The impact of chronic hepatitis C infection on the circadian clock and sleep.

PMID- 24434504
TI  - Extraneural metastases of primary central nervous system tumors identified by
      fine needle aspiration: a retrospective analysis.
AB  - OBJECTIVE: Extraneural metastasis (EM) of primary central nervous system (PCNS)
      neoplasms is rare and signifies a poor clinical outcome. Due to its infrequent
      occurrence, relatively few reports on the cytomorphology of these neoplasms have
      been published. We describe a series of 19 cases from 16 patients at a single,
      large tertiary care center. STUDY DESIGN: A retrospective analysis of 19 cases of
      metastases from PCNS neoplasms identified on fine needle aspiration (FNA) in 8
      male and 8 female patients aged 14-72 years (mean age 39.6) from 1989 to 2013 was
      conducted to further characterize the cytomorphologic features identified at
      metastatic sites. RESULTS: Six different PCNS neoplasms were identified:
      meningioma, glioblastoma, hemangiopericytoma (HPC), oligodendroglioma,
      medulloblastoma, and retinoblastoma. The mean latency period between the
      diagnoses of the primary and first metastatic tumors was 7.4 years (range 0-15).
      The most common PCNS malignancy responsible for EM was HPC. The most common
      metastatic sites were the lung (31%) and soft tissue/bone (31%). CONCLUSIONS: EM
      of PCNS tumors is extremely rare. FNA allows for quick, safe and accurate
      diagnosis. Cytomorphologic features are characteristic, and in conjunction with
      the clinical history and immunohistochemistry, an accurate diagnosis was obtained
      in 100% of the cases.

PMID- 24434503
TI  - A randomized, double-blind, multiple-dose study of the pan-genotypic NS5A
      inhibitor samatasvir in patients infected with hepatitis C virus genotype 1, 2, 3
      or 4.
AB  - BACKGROUND & AIMS: Samatasvir is a pan-genotypic inhibitor of the hepatitis C
      (HCV) non-structural protein 5A (NS5A). This study evaluated the antiviral
      activity, pharmacokinetics and safety of samatasvir monotherapy in treatment
      naive subjects infected with HCV genotype 1-4. METHODS: Thirty-four genotype 1
      and thirty genotype 2, 3 or 4 subjects were randomized to receive for 3days
      placebo or samatasvir 25-100mg per day. Plasma samples for HCV RNA,
      pharmacokinetics and sequencing were collected up to day 10. RESULTS: Samatasvir
      achieved potent antiviral activity across genotypes: mean maximum reductions from
      baseline were 3.2-3.6 (genotype 1a), 3.0-4.3 (genotype 1b), 3.2-3.4 (genotype 3),
      and 3.6-3.9 (genotype 4) log10/ml respectively; no viral rebound was observed
      during the 3-day treatment period. For genotype 2 HCV, samatasvir was active in
      subjects with NS5A L31 polymorphism at baseline (individual range 2.5-4.1
      log10/ml), but showed minimal activity in those with baseline M31 polymorphism.
      Samatasvir exhibited a long plasma half-life of approximately 20h which supports
      once daily dosing. Samatasvir was well tolerated in all subjects with no safety
      related discontinuations or serious adverse events. The most common adverse
      events included constipation, nausea and headache and occurred at similar
      frequency in active and placebo subjects. All events were mild or moderate in
      intensity. There were no patterns or dose dependence of adverse events, vital
      signs, laboratory parameters or electrocardiograms. CONCLUSIONS: Samatasvir 25
      100mg monotherapy for 3days was well tolerated and induced a rapid and profound
      reduction in plasma HCV RNA in subjects infected with HCV genotype 1-4.
      Samatasvir is being evaluated in combination with other direct-acting antiviral
      agents in subjects with HCV infection.

PMID- 24434505
TI  - Assembly of chemically modified G-rich sequences into tetramolecular DNA G
      quadruplexes and higher order structures.
AB  - In this review, we introduce the biophysical and biochemical methods currently
      used to investigate the structures and stabilities of tetramolecular DNA G
      quadruplexes containing chemical modifications. We hope this paper will guide
      others as they perform similar experiments leading to more information about the
      effects of chemical modifications on G-quadruplex formation. The structures of
      tetramolecular quadruplexes and some higher order structures based on
      tetramolecular quadruplexes are also described. 

PMID- 24434506
TI  - Cell lines.
AB  - We review the properties and uses of cell lines in Drosophila research,
      emphasizing the variety of lines, the large body of genomic and transcriptional
      data available for many of the lines, and the variety of ways the lines have been
      used to provide tools for and insights into the developmental, molecular, and
      cell biology of Drosophila and mammals. 

PMID- 24434507
TI  - Comparing mRNA levels using in situ hybridization of a target gene and co-stain.
AB  - In situ hybridization is an important technique for measuring the spatial
      expression patterns of mRNA in cells, tissues, and whole animals. However, mRNA
      levels cannot be compared across experiments using typical protocols. Here we
      present a semi-quantitative method to compare mRNA levels of a gene across
      multiple samples. This method yields an estimate of the error in the measurement
      to allow statistical comparison. Our method uses a typical in situ hybridization
      protocol to stain for a target gene and an internal standard, which we refer to
      as a co-stain. As a proof of concept, we apply this method to multiple lines of
      transgenic Drosophila embryos, harboring constructs that express reporter genes
      to different levels. We generated this test set by mutating enhancer sequences to
      contain different numbers of binding sites for Zelda, a transcriptional
      activator. We demonstrate that using a co-stain with in situ hybridization is an
      effective method to compare mRNA levels across samples. This method requires only
      minor modifications to existing in situ hybridization protocols and uses
      straightforward analysis techniques. This strategy can be broadly applied to
      detect quantitative, spatially resolved changes in mRNA levels. 

PMID- 24434508
TI  - The traditional Chinese medical compound Rocaglamide protects nonmalignant
      primary cells from DNA damage-induced toxicity by inhibition of p53 expression.
AB  - One of the main obstacles of conventional anticancer therapy is the toxicity of
      chemotherapeutics to normal tissues. So far, clinical approaches that aim to
      specifically reduce chemotherapy-mediated toxicities are rare. Recently, a number
      of studies have demonstrated that herbal extracts derived from traditional
      Chinese medicine (TCM) may reduce chemotherapy-induced side effects. Thus, we
      screened a panel of published cancer-inhibiting TCM compounds for their
      chemoprotective potential and identified the phytochemical Rocaglamide (Roc-A) as
      a candidate. We show that Roc-A significantly reduces apoptotic cell death
      induced by DNA-damaging anticancer drugs in primary human and murine cells.
      Investigation of the molecular mechanism of Roc-A-mediated protection revealed
      that Roc-A specifically blocks DNA damage-induced upregulation of the
      transcription factor p53 by inhibiting its protein synthesis. The essential role
      of p53 in Roc-A-mediated protection was confirmed by siRNA knockdown of p53 and
      by comparison of the effects of Roc-A on chemoprotection of splenocytes isolated
      from wild-type and p53-deficient mice. Importantly, Roc-A did not protect p53
      deficient or -mutated cancer cells. Our data suggest that Roc-A may be used as an
      adjuvant to reduce the side effects of chemotherapy in patients with p53
      deficient or -mutated tumors. 

PMID- 24434509
TI  - Pretubulysin: a new option for the treatment of metastatic cancer.
AB  - Tubulin-binding agents such as taxol, vincristine or vinblastine are well
      established drugs in clinical treatment of metastatic cancer. However, because of
      their highly complex chemical structures, the synthesis and hence the supply
      issues are still quite challenging. Here we set on stage pretubulysin, a
      chemically accessible precursor of tubulysin that was identified as a potent
      microtubule-binding agent produced by myxobacteria. Although much simpler in
      chemical structure, pretubulysin abrogates proliferation and long-term survival
      as well as anchorage-independent growth, and also induces anoikis and apoptosis
      in invasive tumor cells equally potent to tubulysin. Moreover, pretubulysin
      posseses in vivo efficacy shown in a chicken chorioallantoic membrane (CAM) model
      with T24 bladder tumor cells, in a mouse xenograft model using MDA-MB-231 mammary
      cancer cells and finally in a model of lung metastasis induced by 4T1 mouse
      breast cancer cells. Pretubulysin induces cell death via the intrinsic apoptosis
      pathway by abrogating the expression of pivotal antiapoptotic proteins, namely
      Mcl-1 and Bcl-xL, and shows distinct chemosensitizing properties in combination
      with TRAIL in two- and three-dimensional cell culture models. Unraveling the
      underlying signaling pathways provides novel information: pretubulysin induces
      proteasomal degradation of Mcl-1 by activation of mitogen-activated protein
      kinase (especially JNK (c-Jun N-terminal kinase)) and phosphorylation of Mcl-1,
      which is then targeted by the SCF(Fbw7) E3 ubiquitin ligase complex for
      ubiquitination and degradation. In sum, we designate the microtubule
      destabilizing compound pretubulysin as a highly promising novel agent for mono
      treatment and combinatory treatment of invasive cancer.

PMID- 24434510
TI  - Ankrd2 is a modulator of NF-kappaB-mediated inflammatory responses during muscle
      differentiation.
AB  - Adaptive responses of skeletal muscle regulate the nuclear shuttling of the
      sarcomeric protein Ankrd2 that can transduce different stimuli into specific
      adaptations by interacting with both structural and regulatory proteins. In a
      genome-wide expression study on Ankrd2-knockout or -overexpressing primary
      proliferating or differentiating myoblasts, we found an inverse correlation
      between Ankrd2 levels and the expression of proinflammatory genes and identified
      Ankrd2 as a potent repressor of inflammatory responses through direct interaction
      with the NF-kappaB repressor subunit p50. In particular, we identified Gsk3beta
      as a novel direct target of the p50/Ankrd2 repressosome dimer and found that the
      recruitment of p50 by Ankrd2 is dependent on Akt2-mediated phosphorylation of
      Ankrd2 upon oxidative stress during myogenic differentiation. Surprisingly, the
      absence of Ankrd2 in slow muscle negatively affected the expression of cytokines
      and key calcineurin-dependent genes associated with the slow-twitch muscle
      program. Thus, our findings support a model in which alterations in Ankrd2
      protein and phosphorylation levels modulate the balance between physiological and
      pathological inflammatory responses in muscle. 

PMID- 24434511
TI  - Cytolethal distending toxin B as a cell-killing component of tumor-targeted
      anthrax toxin fusion proteins.
AB  - Cytolethal distending toxin (Cdt) is produced by Gram-negative bacteria of
      several species. It is composed of three subunits, CdtA, CdtB, and CdtC, with
      CdtB being the catalytic subunit. We fused CdtB from Haemophilus ducreyi to the N
      terminal 255 amino acids of Bacillus anthracis toxin lethal factor (LFn) to
      design a novel, potentially potent antitumor drug. As a result of this fusion,
      CdtB was transported into the cytosol of targeted cells via the efficient
      delivery mechanism of anthrax toxin. The fusion protein efficiently killed
      various human tumor cell lines by first inducing a complete cell cycle arrest in
      the G2/M phase, followed by induction of apoptosis. The fusion protein showed
      very low toxicity in mouse experiments and impressive antitumor effects in a
      Lewis Lung carcinoma model, with a 90% cure rate. This study demonstrates that
      efficient drug delivery by a modified anthrax toxin system combined with the
      enzymatic activity of CdtB has great potential as anticancer treatment and should
      be considered for the development of novel anticancer drugs. 

PMID- 24434512
TI  - Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a
      delayed RIPK1 kinase-dependent apoptosis.
AB  - In human cells, the RIPK1-RIPK3-MLKL-PGAM5-Drp1 axis drives tumor necrosis factor
      (TNF)-induced necroptosis through mitochondrial fission, but whether this pathway
      is conserved among mammals is not known. To answer this question, we analyzed the
      presence and functionality of the reported necroptotic axis in mice. As in
      humans, knockdown of receptor-interacting kinase-3 (RIPK3) or mixed lineage
      kinase domain like (MLKL) blocks TNF-induced necroptosis in L929 fibrosarcoma
      cells. However, repression of either of these proteins did not protect the cells
      from death, but instead induced a switch from TNF-induced necroptosis to receptor
      interacting kinase-1 (RIPK1) kinase-dependent apoptosis. In addition, although
      mitochondrial fission also occurs during TNF-induced necroptosis in L929 cells,
      we found that knockdown of phosphoglycerate mutase 5 (PGAM5) and dynamin 1 like
      protein (Drp1) did not markedly protect the cells from TNF-induced necroptosis.
      Depletion of Pink1, a reported interactor of both PGAM5 and Drp1, did not affect
      TNF-induced necroptosis. These results indicate that in these murine cells
      mitochondrial fission and Pink1 dependent processes, including Pink-Parkin
      dependent mitophagy, apparently do not promote necroptosis. Our data demonstrate
      that the core components of the necrosome (RIPK1, RIPK3 and MLKL) are crucial to
      induce TNF-dependent necroptosis both in human and in mouse cells, but the
      associated mechanisms may differ between the two species or cell types. 

PMID- 24434513
TI  - Osteolytic bone metastasis is hampered by impinging on the interplay among
      autophagy, anoikis and ossification.
AB  - Here we show that the fate of osteolytic bone metastasis depends on the balance
      among autophagy, anoikis resistance and ossification, and that the hepatocyte
      growth factor (HGF) signaling pathway seems to have an important role in
      orchestrating bone colonization. These findings are consistent with the
      pathophysiology of bone metastasis that is influenced by the cross-talk of
      supportive and neoplastic cells through molecular signaling networks. We adopted
      the strategy to target metastasis and stroma with the use of adenovirally
      expressed NK4 (AdNK4) and Dasatinib to block HGF/Met axis and Src activity. In
      human bone metastatic 1833 cells, HGF conferred anoikis resistance via Akt and
      Src activities and HIF-1alpha induction, leading to Bim isoforms degradation.
      When Src and Met activities were inhibited with Dasatinib, the Bim isoforms
      accumulated conferring anoikis sensitivity. The proviability effect of HGF, under
      low-nutrient stress condition, was related to a faster autophagy deactivation
      with respect to HGF plus Dasatinib. In the 1833 xenograft model, AdNK4 switched
      metastasis vasculature to blood lacunae, increasing HIF-1alpha in metastasis. The
      combination of AdNK4 plus Dasatinib gave the most relevant results for mice
      survival, and the following molecular and cellular changes were found to be
      responsible. In bone metastasis, we observed a hypoxic condition - marked by HIF
      1alpha - and an autophagy failure - marked by p62 without Beclin-1. Then,
      osteolytic bone metastases were largely prevented, because of autophagy failure
      in metastasis and ossification in bone marrow, with osteocalcin deposition. The
      abnormal repair process was triggered by the dysfunctional autophagy/anoikis
      interplay. In conclusion, the concomitant blockade of HGF/Met axis and Src
      activity seemed to induce HIF-1alpha in metastasis, whereas the bone marrow
      hypoxic response was reduced. As a consequence, anoikis resistance might be
      hampered favoring, instead, autophagy failure and neoformation of woven bone
      trabeculae. Mice survival was, therefore, prolonged by overcoming an escape
      strategy adopted by metastatic cells by disruption of tumor-stroma coevolution,
      showing the importance of autophagy inhibition for the therapy of bone
      metastasis. 

PMID- 24434515
TI  - Weakened rate-dependent depression of Hoffmann's reflex and increased motoneuron
      hyperactivity after motor cortical infarction in mice.
AB  - Abnormal reflexes associated with spasticity are considered a major determinant
      of motor impairments occurring after stroke; however, the mechanisms underlying
      post-stroke spasticity remain unclear. This may be because of the lack of
      suitable rodent models for studying spasticity after cortical injuries. Thus, the
      purpose of the present study was to establish an appropriate post-stroke
      spasticity mouse model. We induced photothrombotic injury in the rostral and
      caudal forelimb motor areas of mice and used the rate-dependent depression (RDD)
      of Hoffmann's reflex (H-reflex) as an indicator of spastic symptoms. To detect
      motoneuron excitability, we examined c-fos mRNA levels and c-Fos immunoreactivity
      in affected motoneurons using quantitative real-time reverse transcription PCR
      and immunohistochemical analysis, respectively. To confirm the validity of our
      model, we confirmed the effect of the anti-spasticity drug baclofen on H-reflex
      RDDs 1 week post stroke. We found that 3 days after stroke, the RDD was
      significantly weakened in the affected muscles of stroke mice compared with sham
      operated mice, and this was observed for 8 weeks. The c-fos mRNA levels in
      affected motoneurons were significantly increased in stroke mice compared with
      sham-operated mice. Immunohistochemical analysis revealed a significant increase
      in the number of c-Fos-positive motoneurons in stroke mice compared with sham
      operated mice at 1, 2, 4, and 8 weeks after stroke; however, the number of c-Fos
      positive motoneurons on both sides of the brain gradually decreased over time.
      Baclofen treatment resulted in recovery of the weakened RDD at 1 week post
      stroke. Our findings suggest that this is a viable animal model of post-stroke
      spasticity. 

PMID- 24434514
TI  - Advanced oxidation protein products induce intestine epithelial cell death
      through a redox-dependent, c-jun N-terminal kinase and poly (ADP-ribose)
      polymerase-1-mediated pathway.
AB  - Advanced oxidation protein products (AOPPs), a novel protein marker of oxidative
      damage, have been confirmed to accumulate in patients with inflammatory bowel
      disease (IBD), as well as those with diabetes and chronic kidney disease.
      However, the role of AOPPs in the intestinal epithelium remains unclear. This
      study was designed to investigate whether AOPPs have an effect on intestinal
      epithelial cell (IEC) death and intestinal injury. Immortalized rat intestinal
      epithelial (IEC-6) cells and normal Sprague Dawley rats were treated with AOPP
      albumin prepared by incubation of rat serum albumin (RSA) with hypochlorous acid.
      Epithelial cell death, nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase subunit activity, reactive oxygen species (ROS) generation, apoptosis
      related protein expression, and c-jun N-terminal kinase (JNK) phosphorylation
      were detected both in vivo and in vitro. In addition, we measured AOPPs
      deposition and IEC death in 23 subjects with Crohn's disease (CD). Extracellular
      AOPP-RSA accumulation induced apoptosis in IEC-6 cultures. The triggering effect
      of AOPPs was mainly mediated by a redox-dependent pathway, including NADPH
      oxidase-derived ROS generation, JNK phosphorylation, and poly (ADP-ribose)
      polymerase-1 (PARP-1) activation. Chronic AOPP-RSA administration to normal rats
      resulted in AOPPs deposition in the villous epithelial cells and in inflammatory
      cells in the lamina propria. These changes were companied with IEC death,
      inflammatory cellular infiltration, and intestinal injury. Both cell death and
      intestinal injury were ameliorated by chronic treatment with apocynin.
      Furthermore, AOPPs deposition was also observed in IECs and inflammatory cells in
      the lamina propria of patients with CD. The high immunoreactive score of AOPPs
      showed increased apoptosis. Our results demonstrate that AOPPs trigger IEC death
      and intestinal tissue injury via a redox-mediated pathway. These data suggest
      that AOPPs may represent a novel pathogenic factor that contributes to IBD
      progression. Targeting AOPP-induced cellular mechanisms might emerge as a
      promising therapeutic option for patients with IBD. 

PMID- 24434516
TI  - Inhibition of the AIF/CypA complex protects against intrinsic death pathways
      induced by oxidative stress.
AB  - Delayed neuronal cell death largely contributes to the progressive infarct
      development and associated functional impairments after cerebral ischemia or
      brain trauma. Previous studies exposed a key role for the interaction of the
      mitochondrial protein apoptosis-inducing factor (AIF) and cytosolic cyclophilin A
      (CypA) in pathways of programmed cell death in neurons in vitro and in vivo.
      These studies suggested that pro-apoptotic activities of AIF, such as its
      translocation to the nucleus and subsequent DNA degradation, depend on the
      physical interaction of AIF with CypA. Hence, this protein complex may represent
      a new pharmacological target for inhibiting the lethal action of AIF on the brain
      tissue. In this study, we show that the AIF amino-acid residues 370-394 mediate
      the protein complex formation of AIF with CypA. The synthetic AIF(370-394)
      peptide inhibited AIF/CypA complex formation in vitro by binding CypA with a K(D)
      of 12 MUM. Further, the peptide exerted pronounced neuroprotective effects in a
      model of glutamate-induced oxidative stress in cultured HT-22 cells. In this
      model system of AIF-dependent cell death, the AIF(370-394) peptide preserved
      mitochondrial integrity, as detected by measurements of the mitochondrial
      membrane potential and quantification of mitochondrial fragmentation. Further,
      the AIF(370-394) peptide inhibited perinuclear accumulation of fragmented
      mitochondria, mitochondrial release of AIF to the nucleus and glutamate-induced
      cell death to a similar extent as CypA-siRNA. These data indicate that the
      targeting of the AIF-CypA axis is an effective strategy of neuroprotection.

PMID- 24434517
TI  - Plasmodium falciparum signal recognition particle components and anti-parasitic
      effect of ivermectin in blocking nucleo-cytoplasmic shuttling of SRP.
AB  - Signal recognition particle (SRP) is a ubiquitous ribonucleoprotein complex that
      targets proteins to endoplasmic reticulum (ER) in eukaryotes. Here we report that
      Plasmodium falciparum SRP is composed of six polypeptides; SRP9, SRP14, SRP19,
      SRP54, SRP68 and SRP72 and a 303nt long SRP RNA. We generated four transgenic
      parasite lines expressing SRP-GFP chimeric proteins and co-localization studies
      showed the nucleo-cytoplasmic localization for these proteins. The evaluation of
      the effect of known SRP and nuclear import/export inhibitors on P. falciparum
      revealed that ivermectin, an inhibitor of importin alpha/beta mediated nuclear
      import inhibited the nuclear import of PfSRP polypeptides at submicromolar
      concentration, thereby killing the parasites. These findings provide insights
      into dynamic structure of P. falciparum SRP and also raise the possibility that
      ivermectin could be used in combination with other antimalarial agents to control
      the disease. 

PMID- 24434518
TI  - Prostasin may contribute to chemoresistance, repress cancer cells in ovarian
      cancer, and is involved in the signaling pathways of CASP/PAK2-p34/actin.
AB  - Ovarian cancer is the deadliest of gynecologic cancers, largely due to the
      development of drug resistance in chemotherapy. Prostasin may have an essential
      role in the oncogenesis. In this study, we show that prostasin is decreased in an
      ovarian cancer drug-resistant cell line and in ovarian cancer patients with high
      levels of excision repair cross-complementing 1, a marker for chemoresistance.
      Our cell cultural model investigation demonstrates prostasin has important roles
      in the development of drug resistance and cancer cell survival. Forced
      overexpression of prostasin in ovarian cancer cells greatly induces cell death
      (resulting in 99% cell death in a drug-resistant cell line and 100% cell death in
      other tested cell lines). In addition, the surviving cells grow at a much lower
      rate compared with non-overexpressed cells. In vivo studies indicate that forced
      overexpression of prostasin in drug-resistant cells greatly inhibits the growth
      of tumors and may partially reverse drug resistance. Our investigation of the
      molecular mechanisms suggests that prostasin may repress cancer cells and/or
      contribute to chemoresistance by modulating the CASP/P21-activated protein kinase
      (PAK2)-p34 pathway, and thereafter PAK2-p34/JNK/c-jun and PAK2-p34/mlck/actin
      signaling pathways. Thus, we introduce prostain as a potential target for
      treating/repressing some ovarian tumors and have begun to identify their relevant
      molecular targets in specific signaling pathways. 

PMID- 24434519
TI  - Molecular mechanisms of hepatic apoptosis.
AB  - Apoptosis is a prominent feature of liver diseases. Causative factors such as
      alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can
      induce apoptotic cell death via membrane receptors and intracellular stress.
      Apoptotic signaling network, including membrane death receptor-mediated cascade,
      reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress,
      lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each
      other, but one mechanism may dominate at a particular stage. Mechanisms of
      hepatic apoptosis are complicated by multiple signaling pathways. The progression
      of liver disease is affected by the balance between apoptotic and antiapoptotic
      capabilities. Therapeutic options of liver injury are impacted by the clear
      understanding toward mechanisms of hepatic apoptosis. 

PMID- 24434520
TI  - Calcineurin suppresses AMPK-dependent cytoprotective autophagy in cardiomyocytes
      under oxidative stress.
AB  - Calcineurin signalling plays a critical role in the pathogenesis of many
      cardiovascular diseases. Calcineurin has been proven to affect a series of
      signalling pathways and to exert a proapoptotic effect in cardiomyocytes.
      However, whether it is able to regulate autophagy remains largely unknown. Here,
      we report that prolonged oxidative stress-induced activation of calcineurin
      contributes to the attenuation of adaptive AMP-activated protein kinase (AMPK)
      signalling and inhibits autophagy in cardiomyocytes. Primary cardiomyocytes
      exhibited rapid formation of autophagosomes, microtubule-associated protein 1
      light chain 3 (LC3) expression and phosphorylation of AMPK in response to
      hydrogen peroxide (H2O2) treatment. However, prolonged (12 h) H2O2 treatment
      attenuated these effects and was accompanied by a significant increase in
      calcineurin activity and apoptosis. Inhibition of calcineurin by FK506 restored
      AMPK function and LC3 expression, and decreased the extent of apoptosis caused by
      prolonged oxidative stress. In contrast, overexpression of the constitutively
      active form of calcineurin markedly attenuated the increase in LC3 induced by
      short-term (3 h) H2O2 treatment and sensitised cells to apoptosis. In addition,
      FK506 failed to induce autophagy and alleviate apoptosis in cardiomyocytes
      expressing a kinase-dead K45R AMPK mutant. Furthermore, inhibition of autophagy
      by 3-methylanine (3-MA) or by knockdown of the essential autophagy-related gene
      ATG7 abrogated the protective effect of FK506. These findings suggest a novel
      role of calcineurin in suppressing adaptive autophagy during oxidative stress by
      downregulating the AMPK signalling pathway. The results also provide insight into
      how altered calcineurin and autophagic signalling is integrated to control cell
      survival during oxidative stress and may guide strategies to prevent cardiac
      oxidative damage.

PMID- 24434521
TI  - RhoA/ROCK/PTEN signaling is involved in AT-101-mediated apoptosis in human
      leukemia cells in vitro and in vivo.
AB  - R-(-)-gossypol acetic acid (AT-101) is a natural cottonseed product that exhibits
      anticancer activity. However, the molecular mechanism behind the antileukemic
      activity of AT-101 has not been well characterized. In this study, we
      investigated how AT-101 induces apoptosis in human leukemia cells. Exposure to AT
      101 significantly increased apoptosis in both human leukemia cell lines and
      primary human leukemia cells. This increase was accompanied by the activation of
      caspases, cytochrome c release, Bcl2-associated X protein (Bax) translocation,
      myeloid cell leukemia-1 (Mcl-1) downregulation, Bcl-2-associated death promoter
      (Bad) dephosphorylation, Akt inactivation, and RhoA/Rho-associated coiled-coil
      containing protein kinase 1/phosphatase and tensin homolog (RhoA/ROCK1/PTEN)
      activation. RhoA, rather than caspase-3 cleavage, mediated the
      cleavage/activation of ROCK1 that AT-101 induced. Inhibiting RhoA and ROCK1
      activation by C3 exoenzyme (C3) and Y27632, respectively, attenuated the ROCK1
      cleavage/activation, PTEN activity, Akt inactivation, Mcl-1 downregulation, Bad
      dephosphorylation, and apoptosis mediated by AT-101. Knocking down ROCK1
      expression using a ROCK1-specific siRNA also significantly abrogated AT-101
      mediated apoptosis. Constitutively active Akt prevented the AT-101-induced Mcl-1
      downregulation, Bad dephosphorylation, and apoptosis. Conversely, AT-101
      lethality was potentiated by the phosphatidylinositol 3-kinase inhibitor
      LY294002. In vivo, the tumor growth inhibition caused by AT-101 was also
      associated with RhoA/ROCK1/PTEN activation and Akt inactivation in a mouse
      leukemia xenograft model. Collectively, these findings suggest that AT-101 may
      preferentially induce apoptosis in leukemia cells by interrupting the
      RhoA/ROCK1/PTEN pathway, leading to Akt inactivation, Mcl-1 downregulation, Bad
      dephosphorylation, and Bax translocation, which culminate in mitochondrial injury
      and apoptosis. 

PMID- 24434523
TI  - Programming a Pavlovian-like conditioning circuit in Escherichia coli.
AB  - Synthetic genetic circuits are programmed in living cells to perform
      predetermined cellular functions. However, designing higher-order genetic
      circuits for sophisticated cellular activities remains a substantial challenge.
      Here we program a genetic circuit that executes Pavlovian-like conditioning, an
      archetypical sequential-logic function, in Escherichia coli. The circuit design
      is first specified by the subfunctions that are necessary for the single
      simultaneous conditioning, and is further genetically implemented using four
      function modules. During this process, quantitative analysis is applied to the
      optimization of the modules and fine-tuning of the interconnections. Analogous to
      classical Pavlovian conditioning, the resultant circuit enables the cells to
      respond to a certain stimulus only after a conditioning process. We show that,
      although the conditioning is digital in single cells, a dynamically progressive
      conditioning process emerges at the population level. This circuit, together with
      its rational design strategy, is a key step towards the implementation of more
      sophisticated cellular computing. 

PMID- 24434522
TI  - Subcellular expression and neuroprotective effects of SK channels in human
      dopaminergic neurons.
AB  - Small-conductance Ca(2+)-activated K(+) channel activation is an emerging
      therapeutic approach for treatment of neurological diseases, including stroke,
      amyotrophic lateral sclerosis and schizophrenia. Our previous studies showed that
      activation of SK channels exerted neuroprotective effects through inhibition of
      NMDAR-mediated excitotoxicity. In this study, we tested the therapeutic potential
      of SK channel activation of NS309 (25 MUM) in cultured human postmitotic
      dopaminergic neurons in vitro conditionally immortalized and differentiated from
      human fetal mesencephalic cells. Quantitative RT-PCR and western blotting
      analysis showed that differentiated dopaminergic neurons expressed low levels of
      SK2 channels and high levels of SK1 and SK3 channels. Further, protein analysis
      of subcellular fractions revealed expression of SK2 channel subtype in
      mitochondrial-enriched fraction. Mitochondrial complex I inhibitor rotenone (0.5
      MUM) disrupted the dendritic network of human dopaminergic neurons and induced
      neuronal death. SK channel activation reduced mitochondrial membrane potential,
      while it preserved the dendritic network, cell viability and ATP levels after
      rotenone challenge. Mitochondrial dysfunction and delayed dopaminergic cell death
      were prevented by increasing and/or stabilizing SK channel activity. Overall, our
      findings show that activation of SK channels provides protective effects in human
      dopaminergic neurons, likely via activation of both membrane and mitochondrial SK
      channels. Thus, SK channels are promising therapeutic targets for
      neurodegenerative disorders such as Parkinson's disease, where dopaminergic cell
      loss is associated with progression of the disease.

PMID- 24434524
TI  - Safety and efficacy of tolcapone in the long-term use in Parkinson disease: an
      observational study.
AB  - OBJECTIVES: The aim of this observational study was to investigate the safety and
      efficacy of tolcapone under practice conditions. METHODS: This 12-month non
      interventional study was conducted from November 2005 to August 2009. Safety
      parameters were incidence of adverse drug reactions (ADRs), signs and symptoms of
      liver failure, and liver monitoring. Efficacy was evaluated on the basis of the
      assessment by physicians and patients by means of the clinical global impression
      scale. RESULTS: Data from 391 patients were available for evaluation. Fifty-six
      ADRs were documented in 45 patients: most frequently, increase in liver enzymes
      (5.6%), diarrhea (2.6%), and nausea (1.3%). No serious ADRs or fulminant
      hepatotoxicity occurred. Sixteen patients discontinued the treatment with
      tolcapone because of adverse events, thereof 7 because of increase in liver
      enzymes, as prespecified in the protocol. Sixty-two elevations of aspartate
      aminotransferase or alanine aminotransferase occurred in 34 patients (8.7%), most
      of them within the first 3 months after initiating tolcapone. Five patients
      (1.3%) experienced clinically relevant elevations (>2xULN). In most patients with
      minimally elevated transaminase levels, tolcapone was continued, leading to
      normalization of transaminase levels in 74% of these patients. Two patients died
      but without causal relationship to tolcapone. The physicians reported improvement
      of clinical global impression for 71.7% of the patients after 3 months and for
      59.1% of the patients after 12 months. CONCLUSIONS: Under routine practice
      conditions, tolcapone was shown to be safe and effective in patients with
      Parkinson disease. Significant liver transaminase elevations were rare and
      generally returned to normal without intervention in most patients. This study
      confirms the low risk for hepatotoxicity associated with tolcapone.

PMID- 24434525
TI  - Agomelatine is effective in reducing insomnia in abstinent alcohol-dependent
      patients.
AB  - OBJECTIVES: Sleep disorders are a widespread, persistent problem among alcohol
      dependent patients and have been implicated in an increased risk for alcohol
      relapse. The melatonin-agonist agomelatine has been shown to improve overall
      sleep quality without daytime sedation. METHODS: In an off-label therapeutic
      setting, 9 alcohol-dependent patients with chronic sleep disorders received
      nightly doses of between 25 and 50 mg of agomelatine. RESULTS: After 6 weeks of
      agomelatine treatment, the Pittsburgh Sleep Quality Index global score for all
      patients had decreased significantly from a mean (SD) of 13.1 (1.7) to 7.8 (1.7)
      (t = 12.8; P = 0.00). CONCLUSIONS: Agomelatine is a preparation that is not prone
      to abuse. The current pilot investigation shows that agomelatine might offer the
      prospect of becoming a valuable addition to the pharmacological repertoire for
      the treatment of alcohol-dependence-associated insomnia.

PMID- 24434526
TI  - Long-term safety of rivastigmine in parkinson disease dementia: an open-label,
      randomized study.
AB  - OBJECTIVE: This study investigated the long-term safety of rivastigmine (12 mg/d
      capsules, 9.5 mg/24 h patch) and effects on motor symptoms in patients with mild
      to-moderately severe Parkinson disease dementia. METHODS: This was a 76-week,
      prospective, open-label, randomized study in patients aged 50 to 85 years.
      Primary outcomes included incidence of, and discontinuation due to, predefined
      adverse events (AEs) potentially arising from worsening of Parkinson disease
      motor symptoms with capsules. Secondary outcomes included frequency of
      AEs/serious AEs. Efficacy outcomes included Alzheimer's Disease Cooperative Study
      Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI-10), and
      Mattis Dementia Rating Scale (MDRS). RESULTS: Five hundred eighty-three patients
      were randomized to rivastigmine capsules (n = 295) or patch (n = 288). Incidence
      of predefined AEs was 36.1% for capsules, 31.9% for patch; discontinuation due to
      worsening of motor symptoms was 4.4% and 2.4%, respectively. Most common AEs were
      nausea (capsules, 40.5%; patch, 8.3%), tremor (24.5%; 9.7%), fall (17.0%; 20.1%),
      vomiting (15.3%; 2.8%), and application site erythema (0%; 13.9%). Significant
      efficacy in favor of capsules was observed at weeks 24 to 76 on MDRS; 24 and 76
      on NPI-10; weeks 52 and 76 on ADCS-ADL. In patients with Mini-Mental State
      Examination (MMSE) greater than 21, no differences in efficacy on MDRS and ADCS
      ADL were observed at any time point; significant differences in favor of capsules
      were maintained in patients with MMSE less than or equal to 21. CONCLUSIONS: This
      study supports the long-term safety of rivastigmine in Parkinson disease
      dementia. The rate of worsening of motor symptoms was in the range expected due
      to the natural progression of Parkinson disease, no new or unexpected safety
      issues emerged in the long-term.

PMID- 24434527
TI  - Bupropion as an add-on therapy in depressed bipolar disorder type I patients with
      comorbid cocaine dependence.
AB  - OBJECTIVES: The treatment of bipolar disorder type I (BD-I) with a comorbid
      cocaine dependence disorder (CDD) is a challenge in current psychiatric practice.
      Drugs with proven efficacy in manic/mixed episodes, such as atypical
      antipsychotics and mood stabilizers, sometimes do not prevent depressive
      relapses; on the other hand, the use of antidepressants during acute depressive
      episodes may increase the risk of a manic switch. The aim of the present study
      was to investigate the short-term efficacy of bupropion augmentation in acutely
      depressed BD-I patients with co-occurring CDD. METHODS: Twelve depressed BD-I
      patients, with a comorbid CDD, treated with valproate 1000 to 1500 mg/d and
      aripiprazole 10 mg/d, were randomly assigned to receive bupropion 150 mg/d as an
      open-label add-on therapy (n = 5) or to continue their previous treatment (n =
      7). RESULTS: After 4 weeks of observation, patients receiving add-on therapy with
      bupropion have improved in terms of Hamilton Depression Rating Scale scores and
      Drug Abuse Screening Test scores, with respect to those of the comparison group,
      whereas no significant increase of Young Mania Rating Scale scores over time was
      observed. CONCLUSIONS: Our preliminary findings suggest that combining bupropion
      with mood stabilizers and atypical antipsychotics may be a good therapeutic
      option in short-term treatment of depressed BD-I patients with comorbid CDD.

PMID- 24434528
TI  - Reduction in the free radical status and clinical benefit of repeated intrathecal
      triamcinolone acetonide application in patients with progressive multiple
      sclerosis.
AB  - BACKGROUND: Previous open trials performed repeated intrathecal application of
      the sustained release steroid triamcinolone acetonide every third day in patients
      with progressive multiple sclerosis and described enhanced walking abilities.
      OBJECTIVES: The objectives of this study were to demonstrate the efficacy of 5
      triamcinolone administrations every other day and to describe their effects on
      the amount of inducible free radicals in cerebrospinal fluid. SUBJECTS/METHODS:
      Clinical ratings, determinations of maximum walking distance, and execution of an
      instrumental peg insertion test were performed at baseline and on each day after
      a triamcinolone injection in 21 patients with progressive multiple sclerosis.
      Induction of free radicals was assessed in cerebrospinal fluid before each
      triamcinolone application by electron spin resonance spectroscopy. RESULTS:
      Scores for multiple sclerosis improved, walking distance increased, and necessary
      intervals for the peg insertion procedure were shortened. The amount of inducible
      free radicals decreased. CONCLUSIONS: Repeat triamcinolone application improves
      dysfunction of upper and lower extremities even when administered 5 times only
      and in series every other day. The declined potential for free radical synthesis
      may be caused by the anti-inflammatory effect of triamcinolone. It may contribute
      to suppress the smoldering, chronic inflammation, particularly in spinal lesions
      of patients with progressive multiple sclerosis. The enhanced arm function
      hypothetically reflects the effect on cervical and brain lesions due to the
      hypobaric features of triamcinolone.

PMID- 24434529
TI  - A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome.
AB  - OBJECTIVES: Dysregulation of dopaminergic signaling has been hypothesized to
      underlie the motor and phonic tics in Tourette syndrome (TS). The objective of
      this trial was to evaluate the safety and tic-reducing activity of the selective
      dopamine D1 receptor antagonist ecopipam in adults with TS. METHODS: This was a
      multicenter, nonrandomized, open-label study of 50-mg ecopipam daily (weeks 1-2)
      and then 100 mg daily (weeks 3-8), taken orally before bedtime. The primary
      efficacy end point was the change in the Yale Global Tic Severity Scale (YGTSS)
      total tic score. Comorbid psychiatric symptoms and premonitory urges were rated;
      weight, serum metabolic studies, and adverse effects were monitored. RESULTS:
      Eighteen adults (15 men; 15 white, 2 African American, 1 Asian), with a mean age
      of 36.2 years (range, 18-63 years), were enrolled, and 15 completed the study.
      Mean (SD) YGTSS Total Tic score was 30.6 (8.8) at baseline and 25.3 (9.2) at 8
      weeks (2-tailed paired t17 = 4.4; P = 0.0004). Mean (SD) YGTSS impairment score
      was 29.7 (10.9) at baseline and 22.8 (13.7) at final visit (t17 = 2.2; P = 0.04).
      There was no significant change in premonitory urges or psychiatric symptoms.
      Mean change in weight was -0.7 kg (P = 0.07). The most commonly reported adverse
      events were sedation (39%), fatigue (33%), insomnia (33%), somnolence (28%),
      anxiety (22%), headache (22%), and muscle twitching (22%). CONCLUSIONS: In this
      open-label study in adults with TS, tics were reduced after 8 weeks of treatment
      with ecopipam. To confirm safety and efficacy, randomized, double blind, placebo
      controlled trials are warranted.

PMID- 24434530
TI  - Successful use of agomelatine in the treatment of major depression in a woman
      taking tamoxifen: a case report.
AB  - The selective estrogen receptor modulator, tamoxifen, is extensively used for the
      endocrine treatment of all stages of hormone receptor-positive breast cancer.
      Tamoxifen is a mainly inactive prodrug, necessitating metabolism by the
      cytochrome P450 (CYP450) pathway, predominantly the Cytochrome P450 2D6 (CYP2D6),
      into the active metabolites 4-hydroxytamoxifen and, in particular, endoxifen to
      achieve its therapeutic effect. As several women treated with tamoxifen may
      experience depressive symptoms or may have a previous or actual major depressive
      episode with ongoing antidepressant treatment or need for a new-onset therapy,
      the coprescription of an antidepressant drug may be particularly problematic as
      several antidepressants are potent CYP2D6-inhibiting drugs. We herein report a
      case of a patient with major depression and concurrent tamoxifen therapy
      successfully treated with agomelatine monotherapy. 

PMID- 24434531
TI  - Rapid weight gain associated with edema after use of paroxetine and venlafaxine:
      2 case reports.
AB  - Edema is a rarely observed adverse effect of the usage of antidepressant, with
      only few case reports of peripheral edema in the literature. This report included
      2 patients who presented with rapid weight gain related to edema after the use of
      venlafaxine and paroxetine alone. The adverse effects developed within 2 to 3
      weeks after the start of the treatments and completely resolved after their
      discontinuation. 

PMID- 24434532
TI  - Tourette disorder treated with valproic acid.
AB  - Valproic acid was successfully prescribed for a 10-year old boy suffering from
      Tourette's Disorder with a co-morbid bipolar diagnosis. Valproic acid has
      demonstrated efficacy in reducing the total number of motor tics, their
      frequency, intensity, complexity, and impairment in a patient who had failed to
      respond to numerous other medications. Valproic acid may be a useful agent to
      consider for children with treatment-resistant Tourette's disorder. 

PMID- 24434533
TI  - Timing and clinical characteristics of topiramate-induced psychosis in a patient
      with epilepsy and tuberous sclerosis.
AB  - Several lines of scientific evidence showed that topiramate may induce psychotic
      symptoms when used as monotherapy. It has been postulated that this topiramate
      effect may be caused by the inhibition of frontal and prefrontal areas induced by
      topiramate. The clinical history of the patient described shows that topiramate
      may also induce psychosis when used in polytherapy. A 34-year-old man, with
      epilepsy associated to tuberous sclerosis complex and without a previous history
      of mental disorders, presented an acute onset of florid psychotic symptoms,
      including visual and auditory hallucinations, derealization, and
      depersonalization. These symptoms appeared 1 month after the introduction of
      topiramate, added to levetiracetam and carbamazepine, when topiramate reached the
      dose of 200 mg daily. Once topiramate was discontinued, the psychotic symptoms
      disappeared, with no recurrence in a 4-month follow-up. Psychotic symptoms were
      associated with topiramate administration. We hypothesized that psychotic
      symptoms appeared a month after the topiramate introduction because of the slow
      topiramate titration and protective effect of carbamazepine. 

PMID- 24434534
TI  - Designing nanogel carriers for antibacterial applications.
AB  - We have developed a novel and simple synthesis route to create nanosized (~5nm)
      silver nanoparticles (Ag NPs) embedded in a biocompatible nanogel (NG) comprising
      degradable, natural polymers, namely dextran and lysozyme. In this study, we
      prepared hybrid nanogels with varying lysozyme content, evaluated their potential
      to reduce Ag NPs in situ (using ultraviolet-visible spectroscopy, cryo
      transmission electronic microscopy, thermogravimetric analysis and Fourier
      transform infrared spectroscopy) and determined their antibacterial properties
      against Escherichia coli and Staphylococcus aureus. Lysozyme was found to enhance
      nucleation and stabilization of Ag NPs while limiting their growth. As lysozyme
      concentration increased, larger nanogels with greater loading of smaller Ag NPs
      were obtained. The antibacterial properties of hybrid NGs were found to depend
      upon nanogel type and bacterial conditions. Hybrid nanogels with the largest Ag
      NPs showed the lowest minimum inhibition concentration. However, the greatest
      bacterial killing efficiency (up to 100%) occurred within 1h if the bacteria were
      exposed to hybrid nanogels with smaller Ag NPs while agitating the medium. These
      results suggest that nanogel properties as well as antibacterial activity can be
      tuned by varying the lysozyme content. By targeting drug delivery (e.g. ligand
      grafted surface), these nanogels can be used to prevent biofilm formation and
      control infection without the complications (i.e. overexposure) associated with
      classical antibiotic delivery platforms. 

PMID- 24434536
TI  - Mechanical properties of electrospun bilayer fibrous membranes as potential
      scaffolds for tissue engineering.
AB  - Bilayer fibrous membranes of poly(l-lactic acid) (PLLA) were fabricated by
      electrospinning, using a parallel-disk mandrel configuration that resulted in the
      sequential deposition of a layer with fibers aligned across the two parallel
      disks and a layer with randomly oriented fibers, both layers deposited in a
      single process step. Membrane structure and fiber alignment were characterized by
      scanning electron microscopy and two-dimensional fast Fourier transform. Because
      of the intricacies of the generated electric field, bilayer membranes exhibited
      higher porosity than single-layer membranes consisting of randomly oriented
      fibers fabricated with a solid-drum collector. However, despite their higher
      porosity, bilayer membranes demonstrated generally higher elastic modulus, yield
      strength and toughness than single-layer membranes with random fibers. Bilayer
      membrane deformation at relatively high strain rates comprised multiple abrupt
      microfracture events characterized by discontinuous fiber breakage. Bilayer
      membrane elongation yielded excessive necking of the layer with random fibers and
      remarkable fiber stretching (on the order of 400%) in the layer with fibers
      aligned in the stress direction. In addition, fibers in both layers exhibited
      multiple localized necking, attributed to the nonuniform distribution of
      crystalline phases in the fibrillar structure. The high membrane porosity, good
      mechanical properties, and good biocompatibility and biodegradability of PLLA
      (demonstrated in previous studies) make the present bilayer membranes good
      scaffold candidates for a wide range of tissue engineering applications.

PMID- 24434535
TI  - Synthesis of bone-like nanocomposites using multiphosphorylated peptides.
AB  - There is a great need for novel materials for mineralized tissue repair and
      regeneration. Two examples of such tissue, bone and dentin, are highly organized
      hierarchical nanocomposites in which mineral and organic phases interface at the
      molecular level. In contrast, current graft materials are either ceramic powders
      or physical blends of mineral and organic phases with mechanical properties far
      inferior to those of their target tissues. The objective of this study was to
      synthesize composite nanofibrils with highly integrated organic/inorganic phases
      inspired by the mineralized collagen fibrils of bone and dentin. Utilizing our
      understanding of bone and dentin biomineralization, we have first designed
      bioinspired peptides containing 3 Ser-Ser-Asp repeat motifs based on the highly
      phosphorylated protein, dentin phosphophoryn (DPP), found in dentin and alveolar
      bone. We demonstrate that up to 80% of serines in the peptide can be
      phosphorylated by casein kinases. We further tested the ability of these peptides
      to induce biomimetic calcium phosphate mineralization of collagen fibrils. Our
      mineralization studies have revealed that in the presence of these phosphorylated
      peptides, mineralized collagen fibrils structurally similar to the mineralized
      collagen fibrils of bone and dentin were formed. Our results demonstrate that
      using phosphorylated DPP-inspired peptides, we can successfully synthesize
      biomimetic composite nanofibrils with integrated organic and inorganic phases.
      These results provide the first step in the development of biomimetic
      nanostructured materials for mineralized tissue repair and regeneration using
      phosphopeptides. 

PMID- 24434537
TI  - A histological and mechanical analysis of the cardiac lead-tissue interface:
      implications for lead extraction.
AB  - The major risks of pacemaker and implantable cardioverter defibrillator
      extraction are attributable to the fibrotic tissue that encases them in situ, yet
      little is known about the cellular and functional properties of this response. In
      the present research, we performed a histological and mechanical analysis of
      human tissue collected from the lead-tissue interface to better understand this
      process and provide insights for the improvement of lead design and extraction.
      The lead-tissue interface consisted of a thin cellular layer underlying a smooth,
      acellular surface, followed by a circumferentially organized collagen-rich
      matrix. 51.8+/-4.9% of cells were myofibroblasts via immunohistochemistry, with
      these cells displaying a similar circumferential organization. Upon mechanical
      testing, samples exhibited a triphasic force-displacement response consisting of
      a toe region during initial tensioning, a linear elastic region and a yield and
      failure region. Mean fracture load was 5.6+/-2.1N, and mean circumferential
      stress at failure was 9.5+/-4.1MPa. While the low cellularity and fibrotic
      composition of tissue observed herein is consistent with a foreign body reaction
      to an implanted material, the significant myofibroblast response provides a
      mechanical explanation for the contractile forces complicating extractions.
      Moreover, the tensile properties of this tissue suggest the feasibility of
      circumferential mechanical tissue disruption, similar to balloon angioplasty
      devices, as a novel approach to assist with lead extraction. 

PMID- 24434538
TI  - Connexin hemichannel and pannexin channel electrophysiology: how do they differ?
AB  - Connexin hemichannels are postulated to form a cell permeabilization pore for the
      uptake of fluorescent dyes and release of cellular ATP. Connexin hemichannel
      activity is enhanced by low external [Ca(2+)]o, membrane depolarization,
      metabolic inhibition, and some disease-causing gain-of-function connexin
      mutations. This paper briefly reviews the electrophysiological channel
      conductance, permeability, and pharmacology properties of connexin hemichannels,
      pannexin 1 channels, and purinergic P2X7 receptor channels as studied in
      exogenous expression systems including Xenopus oocytes and mammalian cell lines
      such as HEK293 cells. Overlapping pharmacological inhibitory and channel
      conductance and permeability profiles makes distinguishing between these channel
      types sometimes difficult. Selective pharmacology for Cx43 hemichannels (Gap19
      peptide), probenecid or FD&C Blue #1 (Brilliant Blue FCF, BB FCF) for Panx1, and
      A740003, A438079, or oxidized ATP (oATP) for P2X7 channels may be the best way to
      distinguish between these three cell permeabilizing channel types. Endogenous
      connexin, pannexin, and P2X7 expression should be considered when performing
      exogenous cellular expression channel studies. Cell pair electrophysiological
      assays permit the relative assessment of the connexin hemichannel/gap junction
      channel ratio not often considered when performing isolated cell hemichannel
      studies. 

PMID- 24434539
TI  - Gap junction and hemichannel-independent actions of connexins on cell and tissue
      functions--an update.
AB  - Connexins, a family of transmembrane proteins, are components of both gap
      junction channels and hemichannels, which mediate the exchange of ions and small
      molecules between adjacent cells, and between the inside and outside of the cell,
      respectively. Substantial advancements have been made in the comprehension of the
      role of gap junctions and hemichannels in coordinating cellular events. In recent
      years, a plethora of studies demonstrate a role of connexin proteins in the
      regulation of tissue homeostasis that occurs independently of their channel
      activities. This is shown in the context of cell growth, adhesion, migration,
      apoptosis, and signaling. The major mechanisms of these channel-independent
      activities still remain to be discovered. In this review, we provide an updated
      overview on the current knowledge of gap junction- and hemichannel-independent
      functions of connexins, in particular, their effects on tumorigenesis,
      neurogenesis and disease development. 

PMID- 24434540
TI  - Syndromic and non-syndromic disease-linked Cx43 mutations.
AB  - There are now at least 14 distinct diseases linked to germ line mutations in the
      21 genes that encode the connexin (Cx) family of gap junction proteins. This
      review focuses on the links between germ-line mutations in the gene encoding Cx43
      (GJA1) and the human disease termed oculodentodigital dysplasia (ODDD). This
      disease is clinically characterized by soft tissue fusion of the digits, abnormal
      craniofacial bone development, small eyes and loss of tooth enamel. However, the
      disease is considerably more complex and somewhat degenerative as patients often
      suffer from other syndromic effects that include incontinence, glaucoma, skin
      diseases and neuropathies that become more pronounced during aging. The challenge
      continues to be understanding how distinct Cx43 gene mutations cause such a
      diverse range of tissue phenotypes and pathophysiological changes while other
      Cx43-rich organs are relatively unaffected. This review will provide an overview
      of many of these studies and distill some themes and outstanding questions that
      need to be addressed in the coming years. 

PMID- 24434542
TI  - Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression.
AB  - Circulating tumor cells (CTCs) are a promising diagnostic and prognostic
      biomarker for metastatic tumors. We demonstrate that CTCs' diagnostic value might
      be increased through real-time monitoring of CTC dynamics. Using preclinical
      animal models of breast cancer and melanoma and in vivo flow cytometry with
      photoacoustic and fluorescence detection schematics, we show that CTC count does
      not always correlate with the primary tumor size. Individual analysis elucidated
      many cases where the highest level of CTCs was detected before the primary tumor
      starts progressing. This phenomenon could be attributed to aggressive tumors
      developing from cancer stem cells. Furthermore, real-time continuous monitoring
      of CTCs reveals that they occur at highly variable rates in a detection point
      over a period of time (e.g., a range of 0-54 CTCs per 5 min). These same
      fluctuations in CTC numbers were observed in vivo in epithelial and non
      epithelial metastatic tumors, in different stages of tumor progression, and in
      different vessels. These temporal CTC fluctuations can explain false negative
      results of a one-time snapshot test in humans. Indeed, we observed wide
      variations in the number of CTCs in subsequent blood samples taken from the same
      metastatic melanoma patient, with some samples being CTC-free. If these phenomena
      are confirmed in our ongoing in vivo clinical trials, this could support a
      personalized strategy of CTC monitoring for cancer patients. 

PMID- 24434541
TI  - Roles and regulation of lens epithelial cell connexins.
AB  - The avascular lens of the eye is covered anteriorly by an epithelium containing
      nucleated, metabolically active cells. This epithelium contains the first lens
      cells to encounter noxious external stimuli and cells that can develop
      compensatory or protective responses. Lens epithelial cells express the gap
      junction proteins, connexin43 (Cx43) and connexin50 (Cx50). Cx43 and Cx50 form
      gap junction channels and hemichannels with different properties. Although they
      may form heteromeric hemichannels, Cx43 and Cx50 probably do not form heterotypic
      channels in the lens. Cx50 channels make their greatest contribution to
      intercellular communication during the early postnatal period; subsequently, Cx43
      becomes the predominant connexin supporting intercellular communication. Although
      epithelial Cx43 appears dispensable for lens development, Cx50 is critical for
      epithelial cell proliferation and differentiation. Cx43 and Cx50 hemichannels and
      gap junction channels are regulated by multiple different agents. Lens epithelial
      cell connexins contribute to both normal lens physiology and pathology. 

PMID- 24434543
TI  - The role and clinical relevance of disseminated tumor cells in breast cancer.
AB  - Tumor cell dissemination is a common phenomenon observed in most cancers of
      epithelial origin. One-third of breast cancer patients present with disseminated
      tumor cells (DTCs) in bone marrow at time of diagnosis; these patients, as well
      as patients with persistent DTCs, have significantly worse clinical outcome than
      DTC-negative patients. Since DTC phenotype may differ from the primary tumor with
      regard to ER and HER2 status, reevaluation of predictive markers on DTCs may
      optimize treatment choices. In the present review, we report on the clinical
      relevance of DTC detection in breast cancer. 

PMID- 24434544
TI  - Effect of hyperthyroidism on the hypercoagulable state and thromboembolic events
      in patients with atrial fibrillation.
AB  - OBJECTIVE: To clarify whether hyperthyroidism (HT) itself confers an additional
      effect on the hypercoagulable state and the risk of ischemic stroke among
      patients with hyperthyroid atrial fibrillation (AF). METHODS: We prospectively
      evaluated plasma D-dimer levels and thromboembolic events among three groups of
      patients (hyperthyroid AF, n = 62; nonthyroid AF, n = 107, and HT without AF, n =
      100). Plasma D-dimer levels were used to evaluate the hypercoagulable state.
      RESULTS: The D-dimer level was significantly higher in patients with hyperthyroid
      AF than in nonthyroid AF (0.66 +/- 0.06 vs. 0.34 +/- 0.02 mg/l, p < 0.001) and HT
      without AF (0.66 +/- 0.06 vs. 0.27 +/- 0.02 mg/l, p < 0.001). During a 3-year
      follow-up, patients with hyperthyroid AF had a significantly higher incidence of
      ischemic stroke compared with patients with nonthyroid AF (hazard ratio, HR: 3.2,
      95% confidence interval, CI: 1.01-5.59, p = 0.04). Cox regression analysis
      revealed that age (HR: 2.5, 95% CI: 1.01-1.21, p = 0.05), CHADS2-VAS score (HR:
      5.5, 95% CI: 1.51-7.43, p = 0.01) and anticoagulation (HR: 0.45, 95% CI: 0.07
      0.54, p = 0.01) were independent predictors of risk for the occurrence of
      ischemic stroke. CONCLUSIONS: The present study suggests that HT may enhance the
      hypercoagulable state and the risk of ischemic stroke in patients with AF.

PMID- 24434545
TI  - Rosuvastatin suppresses the oxidative response in the venous limb of an
      arteriovenous fistula and enhances the fistula blood flow in diabetic rats.
AB  - OBJECTIVE: The blood flow in the arteriovenous (AV) fistula is significantly
      reduced in diabetic patients. Statins are known to mediate pleiotropic effects in
      the vascular endothelium and attenuate inflammatory responses. This study tested
      the vascular protective effect of rosuvastatin in an experimental model of AV
      fistula. METHODS: One week after the induction of diabetes mellitus (DM) in rats,
      a fistula was created in the abdominal aorta and inferior vena cava. Rats
      received placebo or rosuvastatin (15 mg/kg/day) in chow for 2 weeks. The blood
      flow in the venous segments of the fistula was measured. The expression of
      proinflammatory genes and the generation of superoxide in the venous fistula were
      examined. RESULTS: The blood flow and luminal diameter of the AV fistula was
      significantly enhanced in animals treated with rosuvastatin. Rosuvastatin
      attenuated the expression of inducible nitric oxide synthase, NADPH oxidase, and
      monocyte chemotactic protein-1 in the fistula. The levels of superoxide anions
      and proinflammatory cytokines were also suppressed in rosuvastatin-treated
      animals. Neointimal formation in the AV fistula was not affected following
      treatment with rosuvastatin. CONCLUSIONS: We demonstrated that rosuvastatin
      improves luminal dilatation and blood flow in the AV fistula of subjects with DM.
      These vascular protective effects of rosuvastatin are most likely mediated by the
      attenuation of proinflammatory activities in the remodeled vasculature.

PMID- 24434546
TI  - A dragline-forming mobile robot inspired by spiders.
AB  - Mobility of wheeled or legged machines can be significantly increased if they are
      able to move from a solid surface into a three-dimensional space. Although that
      may be achieved by addition of flying mechanisms, the payload fraction will be
      the limiting factor in such hybrid mobile machines for many applications.
      Inspired by spiders producing draglines to assist locomotion, the paper proposes
      an alternative mobile technology where a robot achieves locomotion from a solid
      surface into a free space. The technology resembles the dragline production
      pathway in spiders to a technically feasible degree and enables robots to move
      with thermoplastic spinning of draglines. As an implementation, a mobile robot
      has been prototyped with thermoplastic adhesives as source material of the
      draglines. Experimental results show that a dragline diameter range of 1.17-5.27
      mm was achievable by the 185 g mobile robot in descending locomotion from the
      solid surface of a hanging structure with a power consumption of 4.8 W and an
      average speed of 5.13 cm min(-1). With an open-loop controller consisting of
      sequences of discrete events, the robot has demonstrated repeatable dragline
      formation with a relative deviation within -4% and a length close to the metre
      scale. 

PMID- 24434547
TI  - Systemic light-chain amyloidosis revealed by progressive nail involvement,
      diffuse alopecia and sicca syndrome: report of an unusual case with a review of
      the literature.
AB  - Immunoglobulin light-chain (AL) amyloidosis is a form of systemic amyloidosis in
      which the fibrils are derived from monoclonal light chains. We report a case of a
      66-year-old woman presenting with nail changes, parchment-like hand changes,
      progressive alopecia and sicca syndrome. Histopathological studies of biopsy
      specimens of the scalp, the nail, minor labial salivary glands and abdominal skin
      revealed deposits of AL kappa-type amyloid. Urine protein electrophoresis
      exhibited a weak band of kappa-type light chains. Based on this striking case, we
      here review the characteristic nail and hair manifestations associated with
      systemic amyloidosis. Knowledge of these signs is important for an early
      diagnosis of systemic amyloidosis, identification of the underlying disease and
      patient management.

PMID- 24434548
TI  - Polycomb silencing: from linear chromatin domains to 3D chromosome folding.
AB  - Polycomb group (PcG) proteins are conserved chromatin factors that regulate key
      developmental genes. Genome wide studies have shown that PcG proteins and their
      associated H3K27me3 histone mark cover long genomic domains. PcG proteins and
      H3K27me3 accumulate in Pc nuclear foci, which are the cellular counterparts of
      genomic domains silenced by PcG proteins. One explanation for how large genomic
      domains form nuclear foci may rely on loops occurring between specific elements
      located within domains. However, recent improvement of the chromosome
      conformation capture (3C) technology, which allowed monitoring genome wide
      contacts depicts a more complex picture in which chromosomes are composed of many
      topologically associating domains (TADs). Chromatin regions marked with H3K27me3
      correspond to one class of TADs and PcG proteins participate in long-range
      interactions of H3K27me3 TADs, whereas insulator proteins seem to be important
      for separating TADs and may also participate in the regulation of intra TAD
      architecture. Recent data converge to suggest that this hierarchical organization
      of chromosome domains plays an important role in genome function during cell
      proliferation and differentiation. 

PMID- 24434549
TI  - TRIM38 inhibits TNFalpha- and IL-1beta-triggered NF-kappaB activation by
      mediating lysosome-dependent degradation of TAB2/3.
AB  - TNFalpha and IL-1beta are two proinflammatory cytokines that play critical roles
      in many diseases, including rheumatoid arthritis and infectious diseases. How
      TNFalpha- and IL-1beta-mediated signaling is finely tuned is not fully
      elucidated. Here, we identify tripartite-motif protein 38 (TRIM38) as a critical
      negative regulator of TNFalpha- and IL-1beta-triggered signaling. Overexpression
      of TRIM38 inhibited activation of NF-kappaB and induction of downstream cytokines
      following TNFalpha and IL-1beta stimulation, whereas knockdown or knockout of
      TRIM38 had the opposite effects. TRIM38 constitutively interacted with critical
      components TGF-beta-activated kinase 1 (TAK1)-binding protein 2/3 (TAB2/3) and
      promoted lysosome-dependent degradation of TAB2/3 independent of its E3 ubiquitin
      ligase activity. Consistently, deficiency of TRIM38 resulted in abolished
      translocation of TAB2 to the lysosome, increased level of TAB2 in cells, and
      enhanced activation of TAK1 after TNFalpha and IL-1beta stimulation. We conclude
      that TRIM38 negatively regulates TNFalpha- and IL-1beta-induced signaling by
      mediating lysosome-dependent degradation of TAB2/3, two critical components in
      TNFalpha- and IL-1beta-induced signaling pathways. Our findings reveal a
      previously undiscovered mechanism by which cells keep the inflammatory response
      in check to avoid excessive harmful immune response triggered by TNFalpha and IL
      1beta. 

PMID- 24434550
TI  - Release of protein A from the cell wall of Staphylococcus aureus.
AB  - Staphylococcal protein A (SpA) is anchored to the cell wall envelope of
      Staphylococcus aureus by sortase A, which links the threonyl (T) of its C
      terminal LPXTG motif to peptidoglycan cross-bridges (i.e., Gly5). SpA binds the
      Fcgamma domains of IgG and protects staphylococci from opsonophagocytic
      clearance. Moreover, SpA cross-links B-cell receptors to modify host adaptive
      immune responses. The mechanisms whereby SpA is released from the bacterial
      surface to access the host's immune system are not known. Here we demonstrate
      that SpA is released with murein tetrapeptide-tetraglycyl [L-Ala-D-iGln-(SpA
      Gly5)L-Lys-D-Ala-Gly4] linked to its C-terminal threonyl. LytN, a cross-wall
      murein hydrolase, contributes to the release of SpA by removing amino sugars
      [i.e., N-acetylmuramic acid-N-acetylglucosamine (MurNAc-GlcNAc)] from attached
      peptidoglycan, whereas LytM, a pentaglycyl-endopeptidase, triggers polypeptide
      release from the bacterial envelope. A model is proposed whereby murein
      hydrolases cleave the anchor structure of released SpA to modify host immune
      responses.

PMID- 24434551
TI  - Carlactone is an endogenous biosynthetic precursor for strigolactones.
AB  - Strigolactones (SLs) are a class of terpenoid plant hormones that regulate shoot
      branching as well as being known as root-derived signals for symbiosis and
      parasitism. SL has tricyclic-lactone (ABC-ring) and methyl butenolide (D-ring),
      and they are connected through an enol ether bridge. Recently, a putative
      biosynthetic intermediate called carlactone (CL), of which carbon skeleton is in
      part similar to those of SLs, was identified by biochemical analysis of three
      biosynthetic enzymes, DWARF27, CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7), and CCD8
      in vitro. However, CL has never been identified from plant tissues, and the
      conversion of CL to SLs has not been proven in vivo. To address these questions,
      we chemically synthesized (13)C-labeled CL. We show that (13)C-labeled CL is
      converted to (-)-[(13)C]-2'-epi-5-deoxystrigol ((-)-2'-epi-5DS) and [(13)C]
      orobanchol, endogenous SLs in rice, in the dwarf10 mutant, which is defective in
      CCD8. In addition, we successfully identified endogenous CL by using liquid
      chromatography-quadrupole/time-of-flight tandem mass spectrometry in rice and
      Arabidopsis. Furthermore, we determined the absolute stereochemistry of
      endogenous CL to be (11R)-configuration, which is the same as that of (-)-2'-epi
      5DS at the corresponding position. Feeding experiments showed that only the (11R)
      isomer of CL, but not the (11S)-isomer, was converted to (-)-2'-epi-5DS in vivo.
      Taken together, our data provide conclusive evidence that CL is an endogenous SL
      precursor that is stereospecifically recognized in the biosynthesis pathway. 

PMID- 24434552
TI  - Crystal structure of the essential transcription antiterminator M2-1 protein of
      human respiratory syncytial virus and implications of its phosphorylation.
AB  - The M2-1 protein of the important pathogen human respiratory syncytial virus is a
      zinc-binding transcription antiterminator that is essential for viral gene
      expression. We present the crystal structure of full-length M2-1 protein in its
      native tetrameric form at a resolution of 2.5 A. The structure reveals that M2-1
      forms a disk-like assembly with tetramerization driven by a long helix forming a
      four-helix bundle at its center, further stabilized by contact between the zinc
      binding domain and adjacent protomers. The tetramerization helix is linked to a
      core domain responsible for RNA binding activity by a flexible region on which
      lie two functionally critical serine residues that are phosphorylated during
      infection. The crystal structure of a phosphomimetic M2-1 variant revealed
      altered charge density surrounding this flexible region although its position was
      unaffected. Structure-guided mutagenesis identified residues that contributed to
      RNA binding and antitermination activity, revealing a strong correlation between
      these two activities, and further defining the role of phosphorylation in M2-1
      antitermination activity. The data we present here identify surfaces critical for
      M2-1 function that may be targeted by antiviral compounds. 

PMID- 24434553
TI  - RIG-I-like receptor LGP2 protects tumor cells from ionizing radiation.
AB  - An siRNA screen targeting 89 IFN stimulated genes in 14 different cancer cell
      lines pointed to the RIG-I (retinoic acid inducible gene I)-like receptor
      Laboratory of Genetics and Physiology 2 (LGP2) as playing a key role in
      conferring tumor cell survival following cytotoxic stress induced by ionizing
      radiation (IR). Studies on the role of LGP2 revealed the following: (i) Depletion
      of LGP2 in three cancer cell lines resulted in a significant increase in cell
      death following IR, (ii) ectopic expression of LGP2 in cells increased resistance
      to IR, and (iii) IR enhanced LGP2 expression in three cell lines tested. Studies
      designed to define the mechanism by which LGP2 acts point to its role in
      regulation of IFNbeta. Specifically (i) suppression of LGP2 leads to enhanced
      IFNbeta, (ii) cytotoxic effects following IR correlated with expression of
      IFNbeta inasmuch as inhibition of IFNbeta by neutralizing antibody conferred
      resistance to cell death, and (iii) mouse embryonic fibroblasts from IFN receptor
      1 knockout mice are radioresistant compared with wild-type mouse embryonic
      fibroblasts. The role of LGP2 in cancer may be inferred from cumulative data
      showing elevated levels of LGP2 in cancer cells are associated with more adverse
      clinical outcomes. Our results indicate that cytotoxic stress exemplified by IR
      induces IFNbeta and enhances the expression of LGP2. Enhanced expression of LGP2
      suppresses the IFN stimulated genes associated with cytotoxic stress by turning
      off the expression of IFNbeta. 

PMID- 24434554
TI  - Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae
      using a C-16alpha hydroxylase from Bupleurum falcatum.
AB  - The saikosaponins comprise oleanane- and ursane-type triterpene saponins that are
      abundantly present in the roots of the genus Bupleurum widely used in Asian
      traditional medicine. Here we identified a gene, designated CYP716Y1, encoding a
      cytochrome P450 monooxygenase from Bupleurum falcatum that catalyzes the C
      16alpha hydroxylation of oleanane- and ursane-type triterpenes. Exploiting this
      hitherto unavailable enzymatic activity, we launched a combinatorial synthetic
      biology program in which we combined CYP716Y1 with oxidosqualene cyclase, P450,
      and glycosyltransferase genes available from other plant species and
      reconstituted the synthesis of monoglycosylated saponins in yeast. Additionally,
      we established a culturing strategy in which applying methylated beta
      cyclodextrin to the culture medium allows the sequestration of heterologous
      nonvolatile hydrophobic terpenes, such as triterpene sapogenins, from engineered
      yeast cells into the growth medium, thereby greatly enhancing productivity.
      Together, our findings provide a sound base for the development of a synthetic
      biology platform for the production of bioactive triterpene sapo(ge)nins. 

PMID- 24434555
TI  - Reconciling disparate views of template-directed nucleation through measurement
      of calcite nucleation kinetics and binding energies.
AB  - The physical basis for how macromolecules regulate the onset of mineral formation
      in calcifying tissues is not well established. A popular conceptual model assumes
      the organic matrix provides a stereochemical match during cooperative
      organization of solute ions. In contrast, another uses simple binding assays to
      identify good promoters of nucleation. Here, we reconcile these two views and
      provide a mechanistic explanation for template-directed nucleation by correlating
      heterogeneous nucleation barriers with crystal-substrate-binding free energies.
      We first measure the kinetics of calcite nucleation onto model substrates that
      present different functional group chemistries (carboxyl, thiol, phosphate, and
      hydroxyl) and conformations (C11 and C16 chain lengths). We find rates are
      substrate-specific and obey predictions of classical nucleation theory at
      supersaturations that extend above the solubility of amorphous calcium carbonate.
      Analysis of the kinetic data shows the thermodynamic barrier to nucleation is
      reduced by minimizing the interfacial free energy of the system, gamma. We then
      use dynamic force spectroscopy to independently measure calcite-substrate-binding
      free energies, DeltaGb. Moreover, we show that within the classical theory of
      nucleation, gamma and DeltaGb should be linearly related. The results bear out
      this prediction and demonstrate that low-energy barriers to nucleation correlate
      with strong crystal-substrate binding. This relationship is general to all
      functional group chemistries and conformations. These findings provide a physical
      model that reconciles the long-standing concept of templated nucleation through
      stereochemical matching with the conventional wisdom that good binders are good
      nucleators. The alternative perspectives become internally consistent when viewed
      through the lens of crystal-substrate binding. 

PMID- 24434556
TI  - Inhibition of master transcription factors in pluripotent cells induces early
      stage differentiation.
AB  - The potential for pluripotent cells to differentiate into diverse specialized
      cell types has given much hope to the field of regenerative medicine.
      Nevertheless, the low efficiency of cell commitment has been a major bottleneck
      in this field. Here we provide a strategy to enhance the efficiency of early
      differentiation of pluripotent cells. We hypothesized that the initial phase of
      differentiation can be enhanced if the transcriptional activity of master
      regulators of stemness is suppressed, blocking the formation of functional
      transcriptomes. However, an obstacle is the lack of an efficient strategy to
      block protein-protein interactions. In this work, we take advantage of the
      biochemical property of seventeen kilodalton protein (Skp), a bacterial molecular
      chaperone that binds directly to sex determining region Y-box 2 (Sox2). The small
      angle X-ray scattering analyses provided a low resolution model of the complex
      and suggested that the transactivation domain of Sox2 is probably wrapped in a
      cleft on Skp trimer. Upon the transduction of Skp into pluripotent cells, the
      transcriptional activity of Sox2 was inhibited and the expression of Sox2 and
      octamer-binding transcription factor 4 was reduced, which resulted in the
      expression of early differentiation markers and appearance of early neuronal and
      cardiac progenitors. These results suggest that the initial stage of
      differentiation can be accelerated by inhibiting master transcription factors of
      stemness. This strategy can possibly be applied to increase the efficiency of
      stem cell differentiation into various cell types and also provides a clue to
      understanding the mechanism of early differentiation. 

PMID- 24434557
TI  - Microbial metabolites control gut inflammatory responses.

PMID- 24434558
TI  - An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release
      and Aire-activated ectopic transcription.
AB  - Aire induces the expression of a large set of autoantigen genes in the thymus,
      driving immunological tolerance in maturing T cells. To determine the full
      spectrum of molecular mechanisms underlying the Aire transactivation function, we
      screened an AIRE-dependent gene-expression system with a genome-scale lentiviral
      shRNA library, targeting factors associated with chromatin architecture/function,
      transcription, and mRNA processing. Fifty-one functional allies were identified,
      with a preponderance of factors that impact transcriptional elongation compared
      with initiation, in particular members of the positive transcription elongation
      factor b (P-TEFb) involved in the release of "paused" RNA polymerases (CCNT2 and
      HEXIM1); mRNA processing and polyadenylation factors were also highlighted
      (HNRNPL/F, SFRS1, SFRS3, and CLP1). Aire's functional allies were validated on
      transfected and endogenous target genes, including the generation of lentigenic
      knockdown (KD) mice. We uncovered the effect of the splicing factor Hnrnpl on
      Aire-induced transcription. Transcripts sensitive to the P-TEFb inhibitor
      flavopiridol were reduced by Hnrnpl knockdown in thymic epithelial cells,
      independently of their dependence on Aire, therefore indicating a general effect
      of Hnrnpl on RNA elongation. This conclusion was substantiated by demonstration
      of HNRNPL interactions with P-TEFb components (CDK9, CCNT2, HEXIM1, and the small
      7SK RNA). Aire-containing complexes include 7SK RNA, the latter interaction
      disrupted by HNRNPL knockdown, suggesting that HNRNPL may partake in delivering
      inactive P-TEFb to Aire. Thus, these results indicate that mRNA processing
      factors cooperate with Aire to release stalled polymerases and to activate
      ectopic expression of autoantigen genes in the thymus. 

PMID- 24434560
TI  - Validity of pHluorin-tagged GluA2 as a reporter for AMPA receptor surface
      expression and endocytosis.

PMID- 24434559
TI  - GRK3 is essential for metastatic cells and promotes prostate tumor progression.
AB  - The biochemical mechanisms that regulate the process of cancer metastasis are
      still poorly understood. Because kinases, and the signaling pathways they
      comprise, play key roles in regulation of many cellular processes, we used an
      unbiased RNAi in vitro screen and a focused cDNA in vivo screen against human
      kinases to identify those with previously undocumented roles in metastasis. We
      discovered that G-protein-coupled receptor kinase 3 (GRK3; or beta-adrenergic
      receptor kinase 2) was not only necessary for survival and proliferation of
      metastatic cells, but also sufficient to promote primary prostate tumor growth
      and metastasis upon exogenous expression in poorly metastatic cells in mouse
      xenograft models. Mechanistically, we found that GRK3 stimulated angiogenesis, at
      least in part through down-regulation of thrombospondin-1 and plasminogen
      activator inhibitor type 2. Furthermore, GRK3 was found to be overexpressed in
      human prostate cancers, especially in metastatic tumors. Taken together, these
      data suggest that GRK3 plays an important role in prostate cancer progression and
      metastasis. 

PMID- 24434561
TI  - Evaluation of multiple reaction monitoring cubed for the analysis of tachykinin
      related peptides in rat spinal cord using a hybrid triple quadrupole-linear ion
      trap mass spectrometer.
AB  - Targeted peptide methods generally use HPLC-MS/MRM approaches. Although dependent
      on the instrumental resolution, interferences may occur while performing analysis
      of complex biological matrices. HPLC-MS/MRM(3) is a technique, which provides a
      significantly better selectivity, compared with HPLC-MS/MRM assay. HPLC-MS/MRM(3)
      allows the detection and quantitation by enriching standard MRM with secondary
      product ions that are generated within the linear ion trap. Substance P (SP) and
      neurokinin A (NKA) are tachykinin peptides playing a central role in pain
      transmission. The objective of this study was to verify whether HPLC-MS/MRM(3)
      could provide significant advantages over a more traditional HPLC-MS/MRM assay
      for the quantification of SP and NKA in rat spinal cord. The results suggest that
      reconstructed MRM(3) chromatograms display significant improvements with the
      nearly complete elimination of interfering peaks but the sensitivity (i.e. signal
      to-noise ratio) was severely reduced. The precision (%CV) observed was between
      3.5% and 24.1% using HPLC-MS/MRM and in the range of 4.3-13.1% with HPLC
      MS/MRM(3), for SP and NKA. The observed accuracy was within 10% of the
      theoretical concentrations tested. HPLC-MS/MRM(3) may improve the assay
      sensitivity to detect difference between samples by reducing significantly the
      potential of interferences and therefore reduce instrumental errors. 

PMID- 24434562
TI  - Determination of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) in human urine
      by ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - A rapid, simple and sensitive method was developed for the determination of 8-iso
      PGF2alpha in urine using ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS); 8-iso-PGF2alpha-d4 was used as the internal standard
      (IS). Chromatographic separation was performed using an Acquity BEH C18 column
      with a mobile phase composition of A: 0.1% acetic acid in methanol:acetonitrile
      (1:1, v:v) and B: 0.1% acetic acid in water (A:B, 32.5:67.5, v:v). Detection was
      performed on a triple-quadrupole tandem mass spectrometer using atmospheric
      pressure chemical ionization (APCI) in negative mode and using multiple reaction
      monitoring (MRM). The MS/MS ion transitions monitored were m/z 353->193 and 357
      >197 for 8-iso-PGF2alpha and IS, respectively. The calibration curve was prepared
      in PBS buffer because of the presence of endogenous concentrations of analyte in
      the control matrix; the internal standard successfully correcting for matrix
      effects. Good linearity was observed over the concentration range of 0.025-20
      ng/mL; the method proving to be accurate and reliable was successfully used in
      support of a pharmacodynamic study in humans.

PMID- 24434563
TI  - A liquid chromatography-mass spectrometry assay for quantification of Exendin[9
      39] in human plasma.
AB  - Exendin[9-39] is a glucagon-like peptide-1 receptor (GLP-R) antagonist and a
      potential therapeutic drug for treatment of congenital hyperinsulism by lowering
      insulin concentration in plasma. A specific and sensitive LC-MS/MS method was
      validated for quantification of Exendin[9-39] in human plasma. Exendin[9-39] and
      the stable isopically labeled internal standard eluted at 9.2 min and were
      analyzed by single reaction monitoring (SRM) of the transitions m/z 842.9->991.8
      and 848.2->998.8, respectively. The calibration curve was linear in the range 15
      1260 ng/mL with a limit of detection of 1.3 ng/mL. The CVs of the standards were
      2.7-13.1% within-run and 3.1-13.2% between-run. The matrix effect was >100% and
      the SPE recovery was 98.4+/-12.9%. In absence of protease inhibitors, short-term
      stability at room temperature was only one hour. Accordingly, samples were kept
      on ice and sample processing was kept below 1h. Human plasma samples from a
      clinical pilot study in which Exendin[9-39] was administered intravenously were
      analyzed and concentrations up to 600 ng/mL were reported Plasma samples from the
      study were stored at -80  degrees C with internal standard and successfully
      reanalyzed after 12 months.

PMID- 24434564
TI  - Development of "one-pot" method for multi-class compounds in porcine formula feed
      by multi-function impurity adsorption cleaning followed ultra-performance liquid
      chromatography-tandem mass spectrometry detection.
AB  - A novel and efficient determination method for multi-class compounds including
      beta-agonists, sedatives, nitro-imidazoles and aflatoxins in porcine formula feed
      based on a fast "one-pot" extraction/multifunction impurity adsorption (MFIA)
      clean-up procedure has been developed. 23 target analytes belonging to four
      different class compounds could be determined simultaneously in a single run.
      Conditions for "one-pot" extraction were studied in detail. Under the optimized
      conditions, the multi-class compounds in porcine formula feed samples were
      extracted and purified with methanol contained ammonia and absorbents by one
      step. The compounds in extracts were purified by using multi types of absorbent
      based on MFIA in one pot. The multi-walled carbon nanotubes were employed to
      improved clean-up efficiency. Shield BEH C18 column was used to separate 23
      target analytes, followed by tandem mass spectrometry (MS/MS) detection using an
      electro-spray ionization source in positive mode. Recovery studies were done at
      three fortification levels. Overall average recoveries of target compounds in
      porcine formula feed at each levels were >51.6% based on matrix fortified
      calibration with coefficients of variation from 2.7% to 13.2% (n=6). The limit of
      determination (LOD) of these compounds in porcine formula feed sample matrix was
      <5.0 MUg/kg. This method was successfully applied in screening and confirmation
      of target drugs in >30 porcine formula feed samples. It was demonstrated that the
      integration of the MFIA protocol with the MS/MS instrument could serve as a
      valuable strategy for rapid screening and reliable confirmatory analysis of multi
      class compounds in real samples.

PMID- 24434565
TI  - Quantitative determination of 11-nor-9-carboxy-tetrahydrocannabinol in hair by
      column switching LC-ESI-MS(3).
AB  - Hair analysis has been regarded as an alternative method to urine analysis in
      forensic and criminal cases. Cannabis (marijuana) is one of the most widely used
      drugs in the world and it has been controlled in South Korea since 1976.
      Identification of 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) in hair can be
      an important proof of cannabis use because it can exclude the possibility of
      passive cannabis smoke exposure. In this study, we described a quantitative
      method of THCCOOH in hair using simple liquid-liquid extraction (LLE), selective
      column switching liquid chromatography with electrospray ionization (ESI)-MS(3).
      For the column switching system three columns (precolumn, trap column and
      analytical column) were used. Valve switch from the precolumn to the trap column
      was set from 3.0 to 4.0 min because THCCOOH appeared around 3.5 min with this
      precolumn. After 4.0 min the valve was switched to the original position and the
      analytes in the trap column were eluted onto the analytical column. Resolution
      occurred in this column and eluted into the ESI-MS(3) system. The internal
      standard was THCCOOH-d3. We used ESI-negative-MS(3) transition of ions at m/z 343
      to 299 to 245 (343/299/245) and m/z 346 to 302 to 248 (346/302/248) for
      quantification of THCCOOH and THCCOOH-d3, respectively. The validation results of
      selectivity, matrix effect, recovery, linearity, precision and accuracy, and
      processed sample stability were satisfactory. The limit of detection (LOD) was
      0.05 pg/mg and the limit of quantification (LOQ) was 0.10 pg/mg. The range of
      concentration of THCCOOH from 98 authentic human hair was 0.13-15.75 pg/mg. This
      method was successfully applied in the analysis of authentic human hair samples.

PMID- 24434566
TI  - Expression, characterization and homology modeling of a novel eukaryotic GH84
      beta-N-acetylglucosaminidase from Penicillium chrysogenum.
AB  - beta-N-acetylglucosaminidases from the family 84 of glycoside hydrolases form a
      small group of glycosidases in eukaryotes responsible for the modification of
      nuclear and cytosolic proteins with O-GlcNAc, thus they are involved in a number
      of important cell processes. Here, the first fungal beta-N-acetylglucosaminidase
      from Penicillium chrysogenum was expressed in Pichia pastoris and secreted into
      the media, purified and characterized. Moreover, homology modeling and substrate
      and inhibitor docking were performed to obtain structural information on this new
      member of the GH84 family. Surprisingly, we found that this fungal beta-N
      acetylglucosaminidase with its sequence and structure perfectly fitting to the
      GH84 family displays biochemical properties rather resembling the beta-N
      acetylhexosaminidases from the family 20 of glycoside hydrolases. This work
      helped to increase the knowledge on the scarcely studied glycosidase family and
      revealed a new type of eukaryotic beta-N-acetylglucosaminidase. 

PMID- 24434567
TI  - Extramedullary myeloma spread triggered by surgical procedures: an emerging
      entity?

PMID- 24434568
TI  - Efficient fully 3D list-mode TOF PET image reconstruction using a factorized
      system matrix with an image domain resolution model.
AB  - A factorized system matrix utilizing an image domain resolution model is
      attractive in fully 3D time-of-flight PET image reconstruction using list-mode
      data. In this paper, we study a factored model based on sparse matrix
      factorization that is comprised primarily of a simplified geometrical projection
      matrix and an image blurring matrix. Beside the commonly-used Siddon's ray
      tracer, we propose another more simplified geometrical projector based on the
      Bresenham's ray-tracer which further reduces the computational cost. We discuss
      in general how to obtain an image blurring matrix associated with a geometrical
      projector, and provide theoretical analysis that can be used to inspect the
      efficiency in model factorization. In simulation studies, we investigate the
      performance of the proposed sparse factorization model in terms of spatial
      resolution, noise properties and computational cost. The quantitative results
      reveal that the factorization model can be as efficient as a non-factored model,
      while its computational cost can be much lower. In addition we conduct Monte
      Carlo simulations to identify the conditions under which the image resolution
      model can become more efficient in terms of image contrast recovery. We verify
      our observations using the provided theoretical analysis. The result offers a
      general guide to achieve the optimal reconstruction performance based on a sparse
      factorization model with an image domain resolution model. 

PMID- 24434569
TI  - Hunger Games.

PMID- 24434570
TI  - The effects on health behavior and health outcomes of Internet-based asynchronous
      communication between health providers and patients with a chronic condition: a
      systematic review.
AB  - BACKGROUND: In support of professional practice, asynchronous communication
      between the patient and the provider is implemented separately or in combination
      with Internet-based self-management interventions. This interaction occurs
      primarily through electronic messaging or discussion boards. There is little
      evidence as to whether it is a useful tool for chronically ill patients to
      support their self-management and increase the effectiveness of interventions.
      OBJECTIVE: The aim of our study was to review the use and usability of patient
      provider asynchronous communication for chronically ill patients and the effects
      of such communication on health behavior, health outcomes, and patient
      satisfaction. METHODS: A literature search was performed using PubMed and Embase.
      The quality of the articles was appraised according to the National Institute for
      Health and Clinical Excellence (NICE) criteria. The use and usability of the
      asynchronous communication was analyzed by examining the frequency of use and the
      number of users of the interventions with asynchronous communication, as well as
      of separate electronic messaging. The effectiveness of asynchronous communication
      was analyzed by examining effects on health behavior, health outcomes, and
      patient satisfaction. RESULTS: Patients' knowledge concerning their chronic
      condition increased and they seemed to appreciate being able to communicate
      asynchronously with their providers. They not only had specific questions but
      also wanted to communicate about feeling ill. A decrease in visits to the
      physician was shown in two studies (P=.07, P=.07). Increases in self
      management/self-efficacy for patients with back pain, dyspnea, and heart failure
      were found. Positive health outcomes were shown in 12 studies, where the clinical
      outcomes for diabetic patients (HbA1c level) and for asthmatic patients (forced
      expiratory volume [FEV]) improved. Physical symptoms improved in five studies.
      Five studies generated a variety of positive psychosocial outcomes. CONCLUSIONS:
      The effect of asynchronous communication is not shown unequivocally in these
      studies. Patients seem to be interested in using email. Patients are willing to
      participate and are taking the initiative to discuss health issues with their
      providers. Additional testing of the effects of asynchronous communication on
      self-management in chronically ill patients is needed.

PMID- 24434571
TI  - The combination of i-leader truncation and gemcitabine improves oncolytic
      adenovirus efficacy in an immunocompetent model.
AB  - Adenovirus (Ad) i-leader protein is a small protein of unknown function. The C
      terminus truncation of the i-leader protein increases Ad release from infected
      cells and cytotoxicity. In the current study, we use the i-leader truncation to
      enhance the potency of an oncolytic Ad. In vitro, an i-leader truncated oncolytic
      Ad is released faster to the supernatant of infected cells, generates larger
      plaques, and is more cytotoxic in both human and Syrian hamster cell lines. In
      mice bearing human tumor xenografts, the i-leader truncation enhances oncolytic
      efficacy. However, in a Syrian hamster pancreatic tumor model, which is
      immunocompetent and less permissive to human Ad, antitumor efficacy is only
      observed when the i-leader truncated oncolytic Ad, but not the non-truncated
      version, is combined with gemcitabine. This synergistic effect observed in the
      Syrian hamster model was not seen in vitro or in immunodeficient mice bearing the
      same pancreatic hamster tumors, suggesting a role of the immune system in this
      synergism. These results highlight the interest of the i-leader C-terminus
      truncation because it enhances the antitumor potency of an oncolytic Ad and
      provides synergistic effects with gemcitabine in the presence of an immune
      competent system. 

PMID- 24434572
TI  - Methylation of SFRP5 is related to multidrug resistance in leukemia cells.
AB  - Methylation of secreted frizzle-related protein (SFRP) genes activates Wnt/beta
      catenin signaling and promotes tumor development. This study investigated whether
      SFRP5 gene methylation causes multidrug resistance (MDR) in leukemia through the
      Wnt/beta-catenin signaling, leading to the upregulation of the mdr1 gene and its
      product, P-glycoprotein (P-gp). Methylation-specific PCR identified SFRP5 gene
      methylation in cultured bone mononuclear cells from 7/12 patients with acute
      leukemia and in four human leukemia cell lines (HL-60, Raji, U937 and KG1a).
      Western blotting revealed absent SFRP5 protein expression in cells from 5/7
      patients with SFRP5 gene methylation and in all cell lines. Treatment with a
      demethylation agent (DAC) rescued SFRP5 expression. mdr1 mRNA and P-gp protein
      were detected in cells from 3/5 patients with absent SFRP5, and in the KG1a cell
      line; these cells also had the highest levels of activated beta-catenin. In cells
      from these three patients, DAC rescued SFRP5 expression and downregulated mdr1
      and P-gp. SFRP5 protein expression was rescued in transgenic KG1a/SFRP5 cells,
      compared with KG1a/eGFP or untransfected KG1a cells. mdr1 and P-gp in KG1a/SFRP5
      cells were downregulated. Doxorubicin IC50 values were significantly lower in
      KG1a/SFRP5 (0.573+/-0.131 MUM) than in KG1a (0.963+/-0.115) or KG1a/eGFP (0.917+/
      0.138) cells (P<0.05). We conclude that SFRP5 gene methylation in leukemia cells
      activates Wnt/beta-catenin signaling to upregulate mdr1/P-gp expression and cause
      MDR. Recovery of SFRP5 expression reversed MDR in the KG1a leukemia cell line.
      Our results suggest that modulating SFRP5 methylation could decrease MDR in
      leukemia patients.

PMID- 24434573
TI  - Depletion of myeloid-derived suppressor cells during interleukin-12 immunogene
      therapy does not confer a survival advantage in experimental malignant glioma.
AB  - Myeloid-derived suppressor cells (MDSCs) accumulate in the glioma
      microenvironment during tumor progression and promote immunosuppression.
      Interleukin-12 (IL-12) immunogene therapy can alter MDSCs toward an antigen
      presenting cell phenotype and these mature cells can have a central role in
      antigen presentation. It remains unclear, however, how MDSC depletion can affect
      glioma immunotherapy. In this study, we generated a replication-deficient
      adenoviral vector, Ad.5/3.cRGD-mIL12p70, that transduces the GL261-based murine
      glioma cell line, resulting in the induction of biologically active, murine
      IL12p70 expression. Ex vivo, IL-12 expressed by GL261 cells induced interferon
      gamma synthesis in CD8(+) T cells (P<0.001), CD4(+) T cells (P=0.009) and natural
      killer cells (P=0.036). When injected 1 week after tumor implantation,
      Ad.5/3.cRGD-mIL12p70 successfully prolonged the survival of glioma-bearing mice.
      Sixty percent of animals treated with IL-12 immunotherapy were long-term
      survivors over 175 days, whereas all the control group animals expired by 40 days
      after tumor implantation (P=0.026). Mice receiving Ad.5/3.cRGD-mIL12p70 also
      accumulated 50% less MDSCs in the brain than the control group (P=0.007).
      Moreover, in the IL-12 group, MDSCs significantly overexpressed CD80 and major
      histocompatibility complex class II molecules (P=0.041). Depletion of MDSCs with
      Gr1(+) antibody had no survival benefit induced by IL-12-mediated immunotherapy.
      Of note, IL-12 therapy increased the presence of myeloid dendritic cells (mDCs)
      in the glioma microenvironment (P=0.0069). Ultimately, the data show that in the
      context of IL-12 immunogene therapy, MDSCs are dispensable and mDCs may provide
      the majority of antigen presentation in the brain. 

PMID- 24434574
TI  - Combination of adenoviruses expressing melanoma differentiation-associated gene-7
      and chemotherapeutic agents produces enhanced cytotoxicity on esophageal
      carcinoma.
AB  - We examined the combinatory antitumor effects of adenoviruses expressing human
      mda-7/IL-24 gene (Ad-mda-7) and chemotherapeutic agents on nine kinds of human
      esophageal carcinoma cells. All the carcinoma cells expressed the melanoma
      differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) receptor
      complexes, IL-20R2 and either IL-20R1 or IL-22R1, and were susceptible to Ad-mda
      7, whereas fibroblasts were positive only for IL-20R2 gene and resistant to Ad
      mda-7-mediated cytotoxicity. Sensitivity of these esophageal carcinoma cells to
      Ad-mda-7 was however lower than that to Ad expressing the wild-type p53 gene. We
      thereby investigated a possible combination of Ad-mda-7 and anticancer agents and
      found that Ad-mda-7 with 5-fluorouracil (5-FU), cisplatin, mitomycin C or
      etoposide produced greater cytotoxic effects than those by Ad-mda-7 or the agent
      alone. Half-maximal inhibitory concentration values of the agents in respective
      cells were decreased by the combination with Ad-mda-7. Cell cycle analyses showed
      that Ad-mda-7 and 5-FU increased G2/M-phase and S-phase populations,
      respectively, and the combination augmented sub-G1 populations. Ad-mda-7-treated
      cells showed cleavages of caspase-8, -9 and -3 and poly (ADP-ribose) polymerase,
      but the cleavage levels were not different from those of the combination-treated
      cells. Ad-mda-7 treatments upregulated Akt phosphorylation but suppressed IkappaB
      alpha levels, whereas 5-FU treatments induced phosphorylation of p53 and
      extracellular signal-regulated protein kinases 1 and 2. Molecular changes caused
      by the combination were similar to those by Ad-mda-7 treatments, but the Ad-mda-7
      mediated upregulation of Akt phosphorylation decreased with the combination.
      These data collectively suggest that Ad-mda-7 induced apoptosis despite Akt
      activation and that the combinatory antitumor effects with 5-FU were produced
      partly by downregulating the Ad-mda-7-induced Akt activation. 

PMID- 24434575
TI  - Complication rate of endosonography (endobronchial and endoscopic ultrasound): a
      systematic review.
AB  - BACKGROUND: Endosonography [endoscopic ultrasound (EUS)-guided fine needle
      aspiration and endobronchial ultrasound (EBUS)-guided transbronchial needle
      aspiration] is increasingly used for lung cancer staging and the assessment of
      sarcoidosis. Serious adverse events (SAE) have been reported in case reports, but
      the true incidence of complications is yet unknown. OBJECTIVES: To assess the
      rate of SAE related to endosonography and to investigate associated risk factors.
      MATERIALS AND METHODS: PubMed, EMBASE and Cochrane libraries were searched for
      eligible references up to April 2012 and these included studies reporting on
      linear EUS or EBUS for the analysis of mediastinal/hilar nodal or central
      intrapulmonary lesions. Case series describing complications were excluded.
      Reported complications were classified into SAE or minor adverse events (AE).
      RESULTS: 190 studies met the inclusion criteria. Information on follow-up was
      missing in half of the studies. In 16,181 patients, 23 SAE (0.14%) and 35 AE
      (0.22%) were reported. No mortality was observed. SAE were more frequent in
      patients investigated with EUS (0.30%) than in those investigated with EBUS
      (0.05%). Infectious SAE were most prevalent (0.07%) and predominantly occurred in
      patients with cystic lesions and sarcoidosis. In lung cancer patients,
      complications were rare. DISCUSSION: Endosonography for intrathoracic nodal
      assessment seems safe for lung cancer patients and mortality has not been
      reported. For cystic lesions and sarcoidosis, there may be a small, but
      nonnegligible risk of infectious complications. The true incidence of SAE might
      be higher as accurate documentation of complications is missing in most studies.

PMID- 24434576
TI  - Second-harmonic generation using 4-quasi-phasematching in a GaAs whispering
      gallery-mode microcavity.
AB  - The 4 crystal symmetry in materials such as GaAs can enable quasi-phasematching
      for efficient optical frequency conversion without poling, twinning or other
      engineered domain inversions. 4 symmetry means that a 90 degrees  rotation is
      equivalent to a crystallographic inversion. Therefore, when light circulates
      about the 4 axis, as in GaAs whispering-gallery-mode microdisks, it encounters
      effective domain inversions that can produce quasi-phasematching. Microdisk
      resonators also offer resonant field enhancement, resulting in highly efficient
      frequency conversion in micrometre-scale volumes. These devices can be integrated
      in photonic circuits as compact frequency convertors, sources of radiation or
      entangled photons. Here we present the first experimental observation of second
      harmonic generation in a whispering-gallery-mode microcavity utilizing -quasi
      phasematching. We use a tapered fibre to couple into the 5-MUm diameter microdisk
      resonator, resulting in a normalized conversion efficiency eta~5 * 10(-5)mW(-1).
      Simulations indicate that when accounting for fibre-cavity scattering, the
      normalized conversion efficiency is eta~3 * 10(-3)mW(-1).

PMID- 24434577
TI  - High-risk mitral valve surgery: what is the role of risk calculators?
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the role of
      established risk scores in assessing patient outcomes following high-risk mitral
      valve surgery. RECENT FINDINGS: The use of risk calculators has become
      increasingly popular in cardiac surgery, particularly in assessing risk for sick
      patients for whom percutaneous therapies may be advantageous. A review of the
      available literature suggests that validated algorithms, namely, the European
      System for Cardiac Operative Risk Evaluation II and Society of Thoracic Surgeons
      models, may have poor discriminatory power in assessing risk for patients
      undergoing high-risk mitral surgery. Therefore, the limitations of these risk
      scores in this population must be taken into consideration. SUMMARY: Current risk
      models provide important insight into the perioperative risk to the patient.
      Further refinement of established risk scores, however, may provide better risk
      prognostication for patients undergoing high-risk mitral valve surgery.

PMID- 24434578
TI  - Surgical approach to functional tricuspid regurgitation: should we be more
      aggressive?
AB  - PURPOSE OF REVIEW: Functional tricuspid regurgitation (FTR) is an important
      clinical entity that is encountered frequently during the operative management of
      left-sided heart valve disease, particularly in the setting of mitral
      regurgitation. Failure to recognize the importance of FTR during mitral valve
      surgery may result in inferior early and late outcomes because of the progression
      of tricuspid regurgitation and right heart failure. In this review, attention is
      focused on recent literature, which increasingly supports the use of corrective
      tricuspid valve annuloplasty, and the growing consensus that FTR or tricuspid
      annular dilation should be more aggressively addressed at the time of cardiac
      surgery. RECENT FINDINGS: The European Society of Cardiology and the European
      Association for Cardiothoracic Surgery (ESC/EACTS) 2012 guidelines recommend a
      more proactive approach to tricuspid regurgitation correction and highlight the
      shifting consensus toward more aggressive surgical therapy. Rigid annuloplasty
      rings should be used in favor of flexible bands or DeVega-style repairs.
      Preoperative determinants of clinical outcomes now include echocardiographic
      parameters of tricuspid valve tenting area, and associated right ventricular size
      and function. SUMMARY: Despite data demonstrating inferior outcomes in the
      presence of residual tricuspid regurgitation after cardiac surgery, surgical
      repair for FTR appears to be underutilized. Increased recognition and correction
      of tricuspid regurgitation at the time of surgery is increasingly supported by
      published guidelines, although randomized prospective data are needed to bolster
      current recommendations.

PMID- 24434579
TI  - Control of lipid droplet size in budding yeast requires the collaboration between
      Fld1 and Ldb16.
AB  - The human congenital generalized lipodystrophy type 2 protein seipin (Fld1 in
      budding yeast) controls lipid droplet (LD) size through an unknown mechanism.
      Here, we report that deletion of yeast LDB16/YCL005W, similar to deletion of
      FLD1, causes supersized and small clustered LDs, altered phospholipid metabolism
      and impaired distribution of a subset of LD proteins. Ldb16 is a transmembrane
      protein in the endoplasmic reticulum (ER) that assembles together with Fld1 at ER
      LD contact sites, a region that probably links neutral lipid synthesis with LD
      assembly. The formation of the Fld1-Ldb16 complex involves putative transmembrane
      segments of both proteins, thus, directly contributing to the maintenance of LD
      morphology. The stability of Ldb16 requires Fld1, as Ldb16 is subjected to ER
      associated degradation (ERAD) in the absence of Fld1 but is stabilized when Fld1
      is present. Strikingly, human seipin, but not yeast Fld1, complements the defects
      in LDs in ldb16Delta yeast, implying that seipin can substitute for the function
      of the Fld1-Ldb16 complex. We propose that human seipin might adopt the
      architecture of the yeast Fld1-Ldb16 complex in order to properly maintain the
      size of LDs.

PMID- 24434580
TI  - PIP-box-mediated degradation prohibits re-accumulation of Cdc6 during S phase.
AB  - Cdc6 and Cdt1 initiate DNA replication licensing when cells exit mitosis. In
      cycling cells, Cdc6 is efficiently degraded from anaphase onwards as a result of
      APC/C-Cdh1 activity. When APC/C-Cdh1 is switched off again, at the end of G1
      phase, Cdc6 could thus re-accumulate, risking the re-licensing of DNA as long as
      Cdt1 is present. Here, we carefully investigated the dynamics of Cdt1 and Cdc6 in
      cycling cells. We reveal a novel APC/C-Cdh1-independent degradation pathway that
      prevents nuclear Cdc6 re-accumulation at the G1-S transition and during S phase.
      Similar to Cdt1, nuclear clearance of Cdc6 depends on an N-terminal PIP-box and
      the Cdt2-containing CRL4 complex. When cells reach G2 phase, Cdc6 rapidly re
      accumulates but, at this time, Cdt1 is mostly absent and expression of Cdc6 is
      limited to the cytoplasm. We propose that Cdk1 contributes to the nuclear export
      of Cdc6 at the S-to-G2 transition. In summary, our results show that different
      control mechanisms of Cdc6 restrain erroneous licensing of DNA replication during
      G1, S and G2 phase.

PMID- 24434581
TI  - PIPKIgamma targets to the centrosome and restrains centriole duplication.
AB  - Centriole biogenesis depends on the polo-like kinase (PLK4) and a small group of
      structural proteins. The spatiotemporal regulation of these proteins at pre
      existing centrioles is essential to ensure that centriole duplication occurs once
      per cell cycle. Here, we report that phosphatidylinositol 4-phosphate 5-kinase
      type-1 gamma (PIP5K1C, hereafter referred to as PIPKIgamma) plays an important
      role in centriole fidelity. PIPKIgamma localized in a ring-like pattern in the
      intermediate pericentriolar materials around the proximal end of the centriole in
      G1, S and G2 phases, but not in M phase. This localization was dependent upon an
      association with centrosomal protein of 152 KDa (CEP152). Without detaining cells
      in S or M phase, the depletion of PIPKIgamma led to centriole amplification in a
      manner that was dependent upon PLK4 and spindle assembly abnormal protein 6
      homolog (SAS6). The expression of exogenous PIPKIgamma reduced centriole
      amplification that occurred as a result of endogenous PIPKIgamma depletion,
      hydroxyurea treatment or PLK4 overexpression, suggesting that PIPKIgamma is
      likely to function at the PLK4 level to restrain centriole duplication.
      Importantly, we found that PIPKIgamma bound to the cryptic polo-box domain of
      PLK4 and that this binding reduced the kinase activity of PLK4. Together, our
      findings suggest that PIPKIgamma is a novel negative regulator of centriole
      duplication, which acts by modulating the homeostasis of PLK4 activity.

PMID- 24434582
TI  - Integrin alpha3beta1 controls mRNA splicing that determines Cox-2 mRNA stability
      in breast cancer cells.
AB  - It is unknown how cues from the tumor microenvironment can regulate post
      transcriptional mechanisms, such as alternative splicing, that control genes that
      drive malignant growth. The induction of cyclooxygenase 2 (Cox-2) by integrin
      alpha3beta1 in breast cancer cells can promote tumor progression. We have used
      RNAi to suppress alpha3beta1 in human MDA-MB-231 breast cancer cells and then
      investigated changes in global gene expression. Numerous mRNAs, including Cox-2,
      show altered expression and/or alternative exon usage (AEU) in alpha3beta1
      deficient cells. AEU included patterns predicted to render an mRNA susceptible to
      degradation, such as 3'-UTR variations or retention of elements that target an
      mRNA for nonsense-mediated decay (NMD). PCR-based analysis of alpha3beta1
      deficient cells confirmed changes in Cox-2 mRNA that might target it for NMD,
      including retention of an intron that harbors premature termination codons and
      changes within the 3'-UTR. Moreover, Cox-2 mRNA has reduced stability in
      alpha3beta1-deficient cells, which is partially reversed by knockdown of the
      essential NMD factor UPF1. Our study identifies alpha3beta1-mediated AEU as a
      novel paradigm of integrin-dependent gene regulation that has potential for
      exploitation as a therapeutic target.

PMID- 24434583
TI  - A Pil1-Sle1-Syj1-Tax4 functional pathway links eisosomes with PI(4,5)P2
      regulation.
AB  - Stable compartments of the plasma membrane promote a wide range of cellular
      functions. In yeast cells, cytosolic structures called eisosomes generate
      prominent cortical invaginations of unknown function. Through a series of genetic
      screens in fission yeast, we found that the eisosome proteins Pil1 and Sle1
      function with the synaptojanin-like lipid phosphatase Syj1 and its ligand Tax4.
      This genetic pathway connects eisosome function with the hydrolysis of
      phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] in cells. Defects in
      PI(4,5)P2 regulation led to eisosome defects, and we found that the core eisosome
      protein Pil1 can bind to and tubulate liposomes containing PI(4,5)P2. Mutations
      in components of the Pil1-Sle1-Syj1-Tax4 pathway suppress the growth and
      morphology defects of TORC2 mutants, indicating that eisosome-dependent
      regulation of PI(4,5)P2 feeds into signal transduction pathways. We propose that
      the geometry of membrane invaginations generates spatial and temporal signals for
      lipid-mediated signaling events in cells. 

PMID- 24434584
TI  - Enrichment of biscuits and juice with oat beta-glucan enhances postprandial
      satiety.
AB  - Effects of fibre and beta-glucan on satiety have been reported in many studies,
      but no consensus has been reached. The aim of this study was to examine the
      effects of breakfasts varying in the dose of oat bran (4g or 8g beta-glucan). The
      approach was to study whether the food matrix (solid or liquid) into which the
      oat bran is incorporated influences postprandial satiety in otherwise similar
      meal settings. Thirty healthy females were offered four different breakfasts:
      biscuits+juice (0g beta-glucan), enriched biscuits+juice (4g beta-glucan),
      biscuits+enriched juice (4g beta-glucan) and enriched biscuits+enriched juice (8g
      beta-glucan) in a random order on separate test days. The sensations associated
      with hunger and satiety were evaluated using visual analogue scales (VAS) before
      and after ingesting the test breakfasts and every 30min until 210min. Oat bran
      addition in breakfasts increased postprandial satiety especially when both juice
      and biscuits were enriched (8g of beta-glucan). Addition of oat bran to juice
      enhanced satiety and related feelings more effectively than the addition into
      biscuits. 

PMID- 24434585
TI  - Structure and post-translational modifications of the web silk protein spidroin-1
      from Nephila spiders.
AB  - Spidroin-1 is one of the major ampullate silk proteins produced by spiders for
      use in the construction of the frame and radii of orb webs, and as a dragline to
      escape from predators. Only partial sequences of spidroin-1 produced by Nephila
      clavipes have been reported up to now, and there is no information on post
      translational modifications (PTMs). A gel-based mass spectrometry strategy with
      ETD and CID fragmentation methods were used to sequence and determine the
      presence/location of any PTMs on the spidroin-1. Sequence coverage of 98.06%,
      95.05%, and 98.37% were obtained for N. clavipes, Nephila edulis and for Nephila
      madagascariensis, respectively. Phosphorylation was the major PTM observed with 8
      phosphorylation sites considered reliable on spidroin-1 produced by N. clavipes,
      4 in N. madagascariensis and 2 for N. edulis. Dityrosine and 3,4
      dihydroxyphenylalanine (formed by oxidation of the spidroin-1) were observed,
      although the mechanism by which they are formed (i.e. exposure to UV radiation or
      to peroxidases in the major ampullate silk gland) is uncertain. Herein we present
      structural information on the spidroin-1 produced by three different Nephila
      species; these findings may be valuable for understanding the physicochemical
      properties of the silk proteins and moreover, future designs of recombinantly
      produced spider silk proteins. Biotechnological significance The present
      investigation shows for the first time spidroin structure and post-translational
      modifications observed on the major ampullate silk spidroin-1. The many site
      specific phosphorylations (localized within the structural motifs) along with the
      probably photoinduction of hydroxylations may be relevant for scientists in
      material science, biology, biochemistry and environmental scientists. Up to now
      all the mechanical properties of the spidroin have been characterized without any
      consideration about the existence of PTMs in the sequence of spidroins. Thus,
      these findings for major ampullate silk spidroin-1 from Nephila spiders provide
      the basis for mechanical-elastic property studies of silk for biotechnological
      and biomedical potential applications. This article is part of a Special Issue
      entitled: Proteomics of non-model organisms. 

PMID- 24434586
TI  - MRM validation of targeted nonglycosylated peptides from N-glycoprotein
      biomarkers using direct trypsin digestion of undepleted human plasma.
AB  - A rapid, simple, and reproducible MRM-based validation method for serological
      glycoprotein biomarkers in clinical use was developed by targeting the
      nonglycosylated tryptic peptides adjacent to N-glycosylation sites. Since changes
      in protein glycosylation are known to be associated with a variety of diseases,
      glycoproteins have been major targets in biomarker discovery. We previously found
      that nonglycosylated tryptic peptides adjacent to N-glycosylation sites differed
      in concentration between normal and hepatocellular carcinoma (HCC) plasma due to
      differences in steric hindrance of the glycan moiety in N-glycoproteins to
      tryptic digestion (Lee et al., 2011). To increase the feasibility and
      applicability of clinical validation of biomarker candidates (nonglycosylated
      tryptic peptides), we developed a method to effectively monitor nonglycosylated
      tryptic peptides from a large number of plasma samples and to reduce the total
      analysis time with maximizing the effect of steric hindrance by the glycans
      during digestion of glycoproteins. The AUC values of targeted nonglycosylated
      tryptic peptides were excellent (0.955 for GQYCYELDEK, 0.880 for FEDGVLDPDYPR and
      0.907 for TEDTIFLR), indicating that these could be effective biomarkers for
      hepatocellular carcinoma. This method provides the necessary throughput required
      to validate glycoprotein biomarkers, as well as quantitative accuracy for human
      plasma analysis, and should be amenable to clinical use. BIOLOGICAL SIGNIFICANCE:
      Difficulties in verifying and validating putative protein biomarkers are often
      caused by complex sample preparation procedures required to determine their
      concentrations in a large number of plasma samples. To solve the difficulties, we
      developed MRM-based protein biomarker assays that greatly reduce complex, time
      consuming, and less reproducible sample pretreatment steps in plasma for clinical
      implementation. First, we used undepleted human plasma samples without any
      enrichment procedures. Using nanoLC/MS/MS, we targeted nonglycosylated tryptic
      peptides adjacent to N-linked glycosylation sites in N-linked glycoprotein
      biomarkers, which could be detected in human plasma samples without depleting
      highly abundant proteins. Second, human plasma proteins were digested with
      trypsin without reduction and alkylation procedures to minimize sample
      preparation. Third, trypsin digestion times were shortened so as to obtain
      reproducible results with maximization of the steric hindrance effect of the
      glycans during enzyme digestion. Finally, this rapid and simple sample
      preparation method was applied to validate targeted nonglycosylated tryptic
      peptides as liver cancer biomarker candidates for diagnosis in 40 normal and 41
      hepatocellular carcinoma (HCC) human plasma samples. This strategy provided the
      necessary throughput required to monitor protein biomarkers, as well as
      quantitative accuracy in human plasma analysis. From biomarker discovery to
      clinical implementation, our method will provide a biomarker study platform that
      is suitable for clinical deployment, and can be applied to high-throughput
      approaches.

PMID- 24434587
TI  - Vintage venoms: proteomic and pharmacological stability of snake venoms stored
      for up to eight decades.
AB  - For over a century, venom samples from wild snakes have been collected and stored
      around the world. However, the quality of storage conditions for "vintage" venoms
      has rarely been assessed. The goal of this study was to determine whether such
      historical venom samples are still biochemically and pharmacologically viable for
      research purposes, or if new sample efforts are needed. In total, 52 samples
      spanning 5 genera and 13 species with regional variants of some species (e.g., 14
      different populations of Notechis scutatus) were analysed by a combined proteomic
      and pharmacological approach to determine protein structural stability and
      bioactivity. When venoms were not exposed to air during storage, the proteomic
      results were virtually indistinguishable from that of fresh venom and bioactivity
      was equivalent or only slightly reduced. By contrast, a sample of Acanthophis
      antarcticus venom that was exposed to air (due to a loss of integrity of the
      rubber stopper) suffered significant degradation as evidenced by the proteomics
      profile. Interestingly, the neurotoxicity of this sample was nearly the same as
      fresh venom, indicating that degradation may have occurred in the free N- or C
      terminus chains of the proteins, rather than at the tips of loops where the
      functional residues are located. These results suggest that these and other
      vintage venom collections may be of continuing value in toxin research. This is
      particularly important as many snake species worldwide are declining due to
      habitat destruction or modification. For some venoms (such as N. scutatus from
      Babel Island, Flinders Island, King Island and St. Francis Island) these were the
      first analyses ever conducted and these vintage samples may represent the only
      venom ever collected from these unique island forms of tiger snakes. Such vintage
      venoms may therefore represent the last remaining stocks of some local
      populations and thus are precious resources. These venoms also have significant
      historical value as the Oxyuranus venoms analysed include samples from the first
      coastal taipan (Oxyuranus scutellatus) collected for antivenom production (the
      snake that killed the collector Kevin Budden), as well as samples from the first
      Oxyuranus microlepidotus specimen collected after the species' rediscovery in
      1976. These results demonstrate that with proper storage techniques, venom
      samples can retain structural and pharmacological stability. This article is part
      of a Special Issue entitled: Proteomics of non-model organisms. BIOLOGICAL
      SIGNIFICANCE: 

PMID- 24434588
TI  - Critical roles of mitochondria in brain activities of torpid Myotis ricketti bats
      revealed by a proteomic approach.
AB  - Bats are the only mammals that fly and hibernate. Little is known about their
      overall metabolism in the brain during hibernation. In this study, brain proteins
      of torpid and active Myotis ricketti bats were fractionated and compared using a
      proteomic approach. Results showed that 21% (23 proteins) of identified proteins
      with significant expression changes were associated with amino acid metabolism
      and proteostasis. The expression levels of proteins involved in energy metabolism
      (15 proteins), cytoskeletal structure (18 proteins), and stress response (13
      proteins) were also significantly altered in torpid bats. Over 30% (34 proteins)
      of differentially expressed proteins were associated with mitochondrial
      functions. Various post-translational modifications (PTMs) on PDHB, DLD, and ARG1
      were detected, suggesting that bats use PTMs to regulate protein functions during
      torpor. Antioxidation and stress responses in torpid bats were similar to those
      of hibernated squirrels, suggesting a common strategy adopted by small
      hibernators against brain dysfunction. Since many amino acids that metabolize in
      mitochondria modulate neuronal transmissions, results of this study reveal
      pivotal roles of mitochondria in neural communication, metabolic regulation, and
      brain cell survival during bat hibernation. This article is part of a Special
      Issue entitled: Proteomics of non-model organisms. BIOLOGICAL SIGNIFICANCE: This
      study reveals the mechanisms used by bats to regulate brain activities during
      torpor. These mechanisms include post-translational modifications and
      differential expression of proteins involved in mitochondrial electron transport,
      anaerobic glycolysis, TCA cycle efflux, cytoskeletal plasticity, amino acid
      metabolism, vesicle structure, antioxidation defense, stress response, and
      proteostasis. Our study provides insights in metabolic regulation of flying
      mammals during torpor and common strategies used by small hibernators in response
      to hibernation. This article is part of a Special Issue entitled: Proteomics of
      non-model organisms.

PMID- 24434589
TI  - Characterization of carp seminal plasma proteome in relation to blood plasma.
AB  - The present study for the first time characterizes a diverse cohort of carp
      seminal and blood plasma proteins using the combination of protein fractionation
      by one-dimensional gel electrophoresis and high performance liquid chromatography
      electrospray ionization tandem mass spectrometry. Using this approach, we
      identified 137 proteins in carp seminal plasma and 88 proteins in carp blood
      plasma, most of which were newly identified in fish. Transferrin, serine
      proteinase inhibitors, apolipoproteins, complement C3 and Wap65 were present in
      high abundance in carp seminal plasma. In carp blood plasma, besides these
      proteins, immunoglobulins and macroglobulins were identified as major proteins.
      Comparative analysis of carp seminal and blood plasma proteome performed using 2D
      DIGE revealed that in contrast to mammals the majority (1014 from 1240 spots) of
      carp seminal plasma proteins are blood proteins. Moreover, proteins more abundant
      in seminal plasma (99 from 1240 spots) were identified, including parvalbumin,
      isoforms of apolipoproteins, heat shock proteins, components of antioxidative
      system, matrix metalloproteinases, cathepsin D, enzymes of glycolysis and sperm
      structural proteins. These proteins are involved in the regulation of sperm
      motility, spermatogenesis, maintenance of sperm membrane lipid stability and
      antioxidant protection. This study enhances the basic knowledge concerning fish
      seminal plasma protein composition and their potential role in fish reproduction.
      BIOLOGICAL SIGNIFICANCE: Proteins similar or identical to blood plasma components
      are important for male reproductive physiology. Comparative study of blood and
      seminal plasma is especially justified in fish. Using 2D-DIGE we indicated that,
      in contrast to mammals, in carp seminal plasma most proteins are common for blood
      and seminal plasma, which possibly is related to a lack of accessory glands in
      reproductive tract of most fish. The proteins present in higher abundance in
      seminal plasma can be related to physiology of fish male reproduction including
      regulation of sperm motility, spermatogenesis, maintenance of sperm surface
      composition and antioxidant protection. Application of proteomics analysis to
      identify carp seminal and blood plasma proteins significantly extends current
      knowledge regarding the composition of fish seminal and blood plasma proteins and
      their relationship to higher vertebrates. Moreover, proteomic profiling of carp
      seminal plasma appears to be helpful for further understanding of the role of
      fish seminal plasma proteins in male reproductive tract as well as for
      identification of novel biomarkers for sperm quality.

PMID- 24434590
TI  - Proteolytic events are relevant cellular responses during nervous system
      regeneration of the starfish Marthasterias glacialis.
AB  - The molecular pathways that trigger the amazing intrinsic regenerative ability of
      echinoderm nervous system are still unknown. In order to approach this subject, a
      2D-DIGE proteomic strategy was used, to screen proteome changes during neuronal
      regeneration in vivo, using starfish (Asteroidea, Echinodermata) as a model. A
      total of 528 proteins showed significant variations during radial nerve cord
      regeneration in both soluble and membrane protein-enriched fractions. Several
      functional classes of proteins known to be involved in axon regeneration events
      in other model organisms, such as chordates, were identified for the first time
      in the regenerating echinoderm nervous system. Unexpectedly, most of the
      identified proteins presented a molecular mass either higher or lower than
      expected. Such results suggest a functional modulation through protein post
      translational modifications, such as proteolysis. Among these are proteins
      involved in cytoskeleton and microtubule regulators, axon guidance molecules and
      growth cone modulators, protein de novo synthesis machinery, RNA binding and
      transport, transcription factors, kinases, lipid signaling effectors and proteins
      with neuroprotective functions. In summary, the impact of proteolysis during
      regeneration events is here shown, although requiring further studies to detail
      on the mechanisms involving this post-transcriptional event on nervous system
      regeneration. BIOLOGICAL SIGNIFICANCE: The nervous systems of some organisms
      present a complete inability of neurons to regrow across a lesion site, which is
      the case of the adult mammalian central nervous system (CNS). Expanding our
      knowledge on how other animals regenerate their nervous system offers great
      potential for groundbreaking biomedical applications towards the enhancement of
      mammalian CNS regeneration. In order to approach this subject, a 2D-DIGE
      proteomic strategy was used for the first time, to screen the proteome changes
      during neuronal regeneration in vivo, using starfish (Asteroidea, Echinodermata)
      as a model. We strongly believe in the relevance of our results and have clear
      evidences that this work constitutes a solid basis for new research on starfish
      regenerating nerve cord. We also believe this work will have a significant impact
      not only on the general scientific community as we present here an alternative
      animal model to neurobiology, but also on the scientific community that works
      with echinoderms or closely related marine invertebrates, which are constantly
      searching for specific protein markers of several tissues, thus constituting an
      important advance towards the improvement of large scale protein information of
      unsequenced, but yet not less important organisms.

PMID- 24434591
TI  - Insulin receptor compensates for IGF1R inhibition and directly induces mitogenic
      activity in prostate cancer cells.
AB  - Hyperinsulinemia is a major complication associated with the development of
      insulin resistance. In addition to its normal spectrum of metabolic effects,
      insulin can act as a growth factor and has the ability to promote mitogenic
      activity. Thus, hyperinsulinemia is regarded as a potentially important cancer
      risk factor among diabetic patients. However, the mechanisms of action of insulin
      in the specific context of prostate cancer (PCa) and, in particular, the specific
      receptor that mediates its actions have not been elucidated yet. The aims of this
      study were to investigate whether insulin can directly induce mitogenic
      activities in PCa-derived cell lines and to examine the mechanisms responsible
      for these actions. To this end, we used several PCa-derived cell lines,
      representing early and advanced stages of the disease. Our results indicated that
      insulin induces cell proliferation in a dose-dependent fashion in the LNCaP, C4
      2, and P69 cell lines. We also demonstrated that insulin enabled LNCaP and C4-2
      cells to progress through the cell cycle. Immunoprecipitation assays revealed
      that insulin activated the insulin receptor (INSR), but not the IGF1 receptor
      (IGF1R). In addition, INSR was able to compensate for and mediate IGF1 mitogenic
      signals following IGF1R inhibition. In conclusion, insulin exhibits direct
      mitogenic activities in PCa cells, which are mediated exclusively through the
      INSR. Further research is needed to fully dissect the molecular mechanisms
      underlying the biological actions of insulin in PCa. 

PMID- 24434592
TI  - Preoperative serum receptor activator of nuclear factor-kappaB
      ligand/osteoprotegerin predict stabilization of spontaneously restored sinus
      rhythm in persistent atrial fibrillation patients after mitral valve surgery.
AB  - OBJECTIVE: The osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB
      (RANK)/RANK ligand (RANKL) axis may play an important role in the stabilization
      of restored sinus rhythm (SR) after mitral valve (MV) surgery by stimulating
      atrial fibrillation (AF)-related atrial remodeling in AF patients. Herein, we
      investigated the association between preoperative serum soluble RANKL
      (sRANKL)/OPG and the stabilization of restored SR after MV surgery. METHODS:
      Persistent AF patients who had spontaneously restored SR after MV replacement
      were enrolled (n = 203). Comparison was made between patients without AF
      recurrence (n = 71) and patients experiencing recurrence (n = 132). RESULTS:
      Patients experiencing recurrence had higher serum levels of sRANKL, OPG and
      sRANKL/OPG ratio than patients without recurrence. Multivariate survival
      regression analysis showed that clinical factors such as duration of AF, left
      atrial diameter and left atrial thrombosis, as well as serum sRANKL level and the
      sRANKL/OPG ratio, were independent predictors of AF recurrence. Receiver
      operating characteristic curve analysis showed that the best diagnostic values of
      the serum sRANKL level and the sRANKL/OPG ratio for predicting recurrence were
      3.44 pmol/l and 0.53, respectively. CONCLUSIONS: Patients who had a low
      preoperative serum sRANKL level and sRANKL/OPG ratio are likely to have a stable
      spontaneously restored SR postoperatively. Thus, we suggest that patients at high
      risk of early AF recurrence should be considered for concomitant surgical
      cardioversion during MV surgery.

PMID- 24434593
TI  - Human leptospirosis on Reunion Island: past and current burden.
AB  - Since 1953, leptospirosis has been recognized as a public health problem on
      Reunion Island. In 2004, was implemented a specific surveillance system that
      included systematic reporting and the realization of environmental investigations
      around hospitalized cases. Here, we present the synthesis of historical data and
      the assessment of 9 years of leptospirosis surveillance. From 2004 to 2012, 414
      hospitalized cases were reported. Cases of leptospirosis occurred mostly during
      the rainy season from December to May. Approximately 41% of infections occurred
      at home, 12% of infections occurred during aquatic leisure and 5% of cases were
      linked to professional activities. Furthermore, for 41% of cases, the place of
      infection could not be determined due to the accumulation of residential and non
      residential exposure. Most of the cases of leptospirosis were linked to rural
      areas or traditional, rural occupations. We did not observe a shift to
      recreational leptospirosis as described in some developed countries. According to
      the new surveillance system, the number of reported cases has regularly increased
      since 2004. This situation is in part due to the improvement of the system in the
      first years but also to a real increase in the number of detected cases due to
      the introduction of molecular methods and to increased biological investigation
      into the Dengue-like syndrome by medical practitioners on the island since the
      Chikungunya crisis in 2006. This increase is probably due to surveillance and
      diagnosis biases but need to be carefully monitored. Nevertheless, the
      possibility of an outbreak is always present due to climatic events, such as
      after the "hyacinth" hurricane in 1980. 

PMID- 24434594
TI  - Geospatial interpolation and mapping of tropospheric ozone pollution using
      geostatistics.
AB  - Tropospheric ozone (O3) pollution is a major problem worldwide, including in the
      United States of America (USA), particularly during the summer months. Ozone
      oxidative capacity and its impact on human health have attracted the attention of
      the scientific community. In the USA, sparse spatial observations for O3 may not
      provide a reliable source of data over a geo-environmental region. Geostatistical
      Analyst in ArcGIS has the capability to interpolate values in unmonitored geo
      spaces of interest. In this study of eastern Texas O3 pollution, hourly episodes
      for spring and summer 2012 were selectively identified. To visualize the O3
      distribution, geostatistical techniques were employed in ArcMap. Using ordinary
      Kriging, geostatistical layers of O3 for all the studied hours were predicted and
      mapped at a spatial resolution of 1 kilometer. A decent level of prediction
      accuracy was achieved and was confirmed from cross-validation results. The mean
      prediction error was close to 0, the root mean-standardized-prediction error was
      close to 1, and the root mean square and average standard errors were small. O3
      pollution map data can be further used in analysis and modeling studies. Kriging
      results and O3 decadal trends indicate that the populace in Houston-Sugar Land
      Baytown, Dallas-Fort Worth-Arlington, Beaumont-Port Arthur, San Antonio, and
      Longview are repeatedly exposed to high levels of O3-related pollution, and are
      prone to the corresponding respiratory and cardiovascular health effects.
      Optimization of the monitoring network proves to be an added advantage for the
      accurate prediction of exposure levels. 

PMID- 24434595
TI  - Ninth international symposium on recent advances in environmental health
      research.

PMID- 24434596
TI  - The portrayal of natural environment in the evolution of the ecological public
      health paradigm.
AB  - This paper explores the conceptualization of the natural environment in an
      evolving ecological public health paradigm. The natural environment has long been
      recognized as essential to supporting life, health, and wellbeing. Our
      understanding of the relationship between the natural environment and health has
      steadily evolved from one of an undynamic environment to a more sophisticated
      understanding of ecological interactions.  This evolution is reflected in a
      number of ecological public health models which demonstrate the many external and
      overlapping determinants of human health. Six models are presented here to
      demonstrate this evolution, each model reflecting an increasingly ecological
      appreciation for the fundamental role of the natural environment in supporting
      human health. We conclude that after decades of public health's acceptance of the
      ecological paradigm, we are only now beginning to assemble knowledge of
      sophisticated ecological interdependencies and apply this knowledge to the
      conceptualization and study of the relationship between the natural environment
      and the determinants of human health. 

PMID- 24434598
TI  - Design and control of a bio-inspired soft wearable robotic device for ankle-foot
      rehabilitation.
AB  - We describe the design and control of a wearable robotic device powered by
      pneumatic artificial muscle actuators for use in ankle-foot rehabilitation. The
      design is inspired by the biological musculoskeletal system of the human foot and
      lower leg, mimicking the morphology and the functionality of the biological
      muscle-tendon-ligament structure. A key feature of the device is its soft
      structure that provides active assistance without restricting natural degrees of
      freedom at the ankle joint. Four pneumatic artificial muscles assist dorsiflexion
      and plantarflexion as well as inversion and eversion. The prototype is also
      equipped with various embedded sensors for gait pattern analysis. For the subject
      tested, the prototype is capable of generating an ankle range of motion of 27
      degrees  (14 degrees  dorsiflexion and 13 degrees  plantarflexion). The
      controllability of the system is experimentally demonstrated using a linear time
      invariant (LTI) controller. The controller is found using an identified LTI model
      of the system, resulting from the interaction of the soft orthotic device with a
      human leg, and model-based classical control design techniques. The suitability
      of the proposed control strategy is demonstrated with several angle-reference
      following experiments. 

PMID- 24434599
TI  - Lytic peptidase L5 of Lysobacter sp. XL1 with broad antimicrobial spectrum.
AB  - The Gram-negative bacterium Lysobacter sp. XL1 secretes lytic enzymes (L1-L5)
      into the culture medium. Enzyme L5 is the most recently found extracellular lytic
      enzyme of this bacterium. The paper presents the results of the isolation and
      characterization of some properties of this enzyme. Thus, enzyme L5 of Lysobacter
      sp. XL1 is a lytic serine protease. Earlier, the enzyme was shown to be secreted
      into the culture medium by means of outer membrane vesicles, which possess a
      lytic effect towards living cells of Erwinia caratovora B15 [Vasilyeva et al.,
      FEBS J 2008;15:3827-3835]. This work shows the action of enzyme L5 either as a
      vesicle component or the homogeneous enzyme L5 on a broad range of Gram-positive
      and Gram-negative microorganisms. Moreover, the vesicles containing this enzyme
      were shown to lyze the selected test cultures more efficiently than the soluble
      enzyme L5. It appears to be one of the first precedents of a bacteriolytic effect
      mediated by the action of outer membrane vesicles filled with extracellular lytic
      enzymes. The results suggest that the enzyme L5 of Lysobacter sp. XL1 and the
      vesicles containing this enzyme can be used as an antimicrobial drug.

PMID- 24434600
TI  - A volume of intersection approach for on-the-fly system matrix calculation in 3D
      PET image reconstruction.
AB  - The aim of this study is the evaluation of on-the-fly volume of intersection
      computation for system's geometry modelling in 3D PET image reconstruction. For
      this purpose we propose a simple geometrical model in which the cubic image
      voxels on the given Cartesian grid are approximated with spheres and the
      rectangular tubes of response (ToRs) are approximated with cylinders. The model
      was integrated into a fully 3D list-mode PET reconstruction for performance
      evaluation. In our model the volume of intersection between a voxel and the ToR
      is only a function of the impact parameter (the distance between voxel centre to
      ToR axis) but is independent of the relative orientation of voxel and ToR. This
      substantially reduces the computational complexity of the system matrix
      calculation. Based on phantom measurements it was determined that adjusting the
      diameters of the spherical voxel size and the ToR in such a way that the actual
      voxel and ToR volumes are conserved leads to the best compromise between high
      spatial resolution, low noise, and suppression of Gibbs artefacts in the
      reconstructed images. Phantom as well as clinical datasets from two different PET
      systems (Siemens ECAT HR(+) and Philips Ingenuity-TF PET/MR) were processed using
      the developed and the respective vendor-provided (line of intersection related)
      reconstruction algorithms. A comparison of the reconstructed images demonstrated
      very good performance of the new approach. The evaluation showed the respective
      vendor-provided reconstruction algorithms to possess 34-41% lower resolution
      compared to the developed one while exhibiting comparable noise levels. Contrary
      to explicit point spread function modelling our model has a simple straight
      forward implementation and it should be easy to integrate into existing
      reconstruction software, making it competitive to other existing resolution
      recovery techniques. 

PMID- 24434597
TI  - Prolactin and teleost ionocytes: new insights into cellular and molecular targets
      of prolactin in vertebrate epithelia.
AB  - The peptide hormone prolactin is a functionally versatile hormone produced by the
      vertebrate pituitary. Comparative studies over the last six decades have revealed
      that a conserved function for prolactin across vertebrates is the regulation of
      ion and water transport in a variety of tissues including those responsible for
      whole-organism ion homeostasis. In teleost fishes, prolactin was identified as
      the "freshwater-adapting hormone", promoting ion-conserving and water-secreting
      processes by acting on the gill, kidney, gut and urinary bladder. In mammals,
      prolactin is known to regulate renal, intestinal, mammary and amniotic epithelia,
      with dysfunction linked to hypogonadism, infertility, and metabolic disorders.
      Until recently, our understanding of the cellular mechanisms of prolactin action
      in fishes has been hampered by a paucity of molecular tools to define and study
      ionocytes, specialized cells that control active ion transport across branchial
      and epidermal epithelia. Here we review work in teleost models indicating that
      prolactin regulates ion balance through action on ion transporters, tight
      junction proteins, and water channels in ionocytes, and discuss recent advances
      in our understanding of ionocyte function in the genetically and embryonically
      accessible zebrafish (Danio rerio). Given the high degree of evolutionary
      conservation in endocrine and osmoregulatory systems, these studies in teleost
      models are contributing novel mechanistic insight into how prolactin participates
      in the development, function, and dysfunction of osmoregulatory systems across
      the vertebrate lineage. 

PMID- 24434601
TI  - Monosymptomatic Persistent Hematospermia due to Rarely Encountered Prostatic
      Utricle Stones.
AB  - We present a young patient who had hematospermia which was unresponsive to
      repeated medical therapies. In this patient prostatic utricle stones were
      detected via pelvic and transrectal ultrasonography, the presence of the stones
      was confirmed by transurethral fenestration, and persistent hematospermia
      disappeared following surgical excision. Thus, we conclude that prostatic utricle
      stones might have caused hematospermia in this young patient, who had no
      additional pathology likely to be responsible for this condition. 

PMID- 24434602
TI  - Towards an accurate understanding of UHMWPE visco-dynamic behaviour for numerical
      modelling of implants.
AB  - Considerable progress has been made in understanding implant wear and developing
      numerical models to predict wear for new orthopaedic devices. However any model
      of wear could be improved through a more accurate representation of the
      biomaterial mechanics, including time-varying dynamic and inelastic behaviour
      such as viscosity and plastic deformation. In particular, most computational
      models of wear of UHMWPE implement a time-invariant version of Archard's law that
      links the volume of worn material to the contact pressure between the metal
      implant and the polymeric tibial insert. During in-vivo conditions, however, the
      contact area is a time-varying quantity and is therefore dependent upon the
      dynamic deformation response of the material. From this observation one can
      conclude that creep deformations of UHMWPE may be very important to consider when
      conducting computational wear analyses, in stark contrast to what can be found in
      the literature. In this study, different numerical modelling techniques are
      compared with experimental creep testing on a unicondylar knee replacement system
      in a physiologically representative context. Linear elastic, plastic and time
      varying visco-dynamic models are benchmarked using literature data to predict
      contact deformations, pressures and areas. The aim of this study is to elucidate
      the contributions of viscoelastic and plastic effects on these surface
      quantities. It is concluded that creep deformations have a significant effect on
      the contact pressure measured (experiment) and calculated (computational models)
      at the surface of the UHMWPE unicondylar insert. The use of a purely
      elastoplastic constitutive model for UHMWPE lead to compressive deformations of
      the insert which are much smaller than those predicted by a creep-capturing
      viscoelastic model (and those measured experimentally). This shows again the
      importance of including creep behaviour into a constitutive model in order to
      predict the right level of surface deformation on a tibial insert. At high
      compressive loads, inelastic deformation mechanisms (creep and plasticity)
      dominate the mechanical response of UHMWPE components by altering the surface
      geometry (penetration depth and so contact area) and therefore the contact
      pressure. Although generic creep models can provide a good first approximation of
      material characteristics, for best accuracy both viscous and plastic effects must
      be captured, and model parameters must be founded upon specific experimental test
      data. Such high-fidelity numerical creep models will provide a better foundation
      for the next generation of more robust and accurate in-silico wear prediction
      tools. 

PMID- 24434605
TI  - ATRA + ATO: has a new standard of care been established in low-risk acute
      promyelocytic leukaemia?
AB  - PURPOSE OF REVIEW: Arsenic trioxide (ATO) has been shown to be the most effective
      single agent in acute promyelocytic leukaemia (APL) and has been approved for the
      treatment of relapsed patients both in the US and Europe. The role of ATO in
      front-line therapy of APL is under investigation. RECENT FINDINGS: Pilot studies
      using ATO with or without all-trans retinoic acid (ATRA) have been carried out in
      newly diagnosed APL patients with the aim to reduce the short and long-term toxic
      effects of chemotherapy and to improve clinical outcome. Especially in patients
      with non-high-risk APL, the ATRA + ATO approach allowed significant increase in
      event-free survival and overall survival rates compared to standard ATRA and
      chemotherapy. This has been demonstrated by pilot studies and, more recently, by
      a randomized comparative multi-centre study conducted in Italy and Germany.
      SUMMARY: The ATO + ATRA strategy for APL may provide the first paradigm of acute
      leukaemia curability by targeted agents and without chemotherapy. However, longer
      follow-up of available studies and independent confirmation of the Italian-German
      findings are awaited to firmly establish this paradigm. Finally, extension of
      this approach to other patient categories such as high-risk, elderly and children
      will need to be explored in the near future.

PMID- 24434606
TI  - Is lack of sleep capable of inducing DNA damage in aged skin?
AB  - Skin naturally changes with age, becoming more fragile. Various stimuli can alter
      skin integrity. The aim of this study was to evaluate whether sleep deprivation
      affects the integrity of DNA in skin and exacerbates the effects of aging.
      Fifteen-month old female Hairless mice underwent 72 h of paradoxical sleep
      deprivation or 15 days of chronic sleep restriction. Punch biopsies of the skin
      were taken to evaluate DNA damage by single cell gel (comet) assay. Neither
      paradoxical sleep deprivation nor sleep restriction increased genetic damage,
      measured by tail movement and tail intensity values. Taken together, the findings
      are consistent with the notion that aging overrides the effect of sleep loss on
      the genetic damage in elderly mice.

PMID- 24434607
TI  - Autaptic self-inhibition of cortical GABAergic neurons: synaptic narcissism or
      useful introspection?
AB  - Fast synaptic inhibition sculpts all forms of cortical activity by means of a
      specialized connectivity pattern between highly heterogeneous inhibitory
      interneurons and principal excitatory cells. Importantly, inhibitory neurons
      connect also to each other extensively, following a detailed blueprint, and,
      indeed, specific forms of disinhibition affect important behavioral functions.
      Here we discuss a peculiar form of cortical disinhibition: the massive autaptic
      self-inhibition of parvalbumin-(PV) positive basket cells. Despite being
      described long ago, autaptic inhibition onto PV basket cells is rarely included
      in cortical circuit diagrams, perhaps because of its still elusive function. We
      propose here a potential dual role of autaptic feedback inhibition in temporally
      coordinating PV basket cells during cortical network activity. 

PMID- 24434608
TI  - Early GABAergic circuitry in the cerebral cortex.
AB  - In the cerebral cortex GABAergic signaling plays an important role in regulating
      early developmental processes, for example, neurogenesis, migration and
      differentiation. Transient cell populations, namely Cajal-Retzius in the marginal
      zone and thalamic input receiving subplate neurons, are integrated as active
      elements in transitory GABAergic circuits. Although immature pyramidal neurons
      receive GABAergic synaptic inputs already at fetal stages, they are integrated
      into functional GABAergic circuits only several days later. In consequence,
      GABAergic synaptic transmission has only a minor influence on spontaneous network
      activity during early corticogenesis. Concurrent with the gradual developmental
      shift of GABA action from excitatory to inhibitory and the maturation of cortical
      synaptic connections, GABA becomes more important in synchronizing neuronal
      network activity. 

PMID- 24434609
TI  - Stereospecific ring expansion from orthocyclophanes with central chirality to
      metacyclophanes with planar chirality.
AB  - Carbon-carbon bonds constitute the major framework of organic molecules and
      carbon-hydrogen bonds are abundant in their peripheries. Such nonpolar sigma
      bonds are thermodynamically stable and kinetically inert in general. Nonetheless,
      selective activation of those ubiquitous bonds may offer a straightforward method
      to construct and/or functionalize organic skeletons. Herein we describe ring
      expansion from orthocyclophanes to metacyclophanes occurring upon sequential
      action of light and a metal catalyst. Formally, specific non-strained carbon
      hydrogen and carbon-carbon bonds are cleaved and exchanged without elimination of
      any leaving groups. Notably, the product is energetically uphill from the
      starting material, but the endergonic photocyclization step makes it possible to
      drive the transformation forward. The ring expansion is extended to the
      stereospecific synthesis of metacyclophanes possessing planar chirality, during
      which central chirality on a tertiary carbon is transferred to planar chirality. 

PMID- 24434610
TI  - Efficacy of bronchoscopic closure of a bronchopleural fistula with amplatzer
      devices: long-term follow-up.
AB  - BACKGROUND: The development of a bronchopleural fistula (BPF) is associated with
      high rates of morbidity and mortality. We have developed a minimally invasive
      method of bronchoscopic BPF closure using Amplatzer devices (AD) and Amplatzer
      vascular plugs (AVP), with excellent short-term results. OBJECTIVES: The aim of
      the present report was to explore the long-term outcome of patients treated by
      Amplatzer occluders and the durability of this novel modality of BPF treatment.
      METHODS: A total of 31 central BPF in 31 patients (mean age 66.8 years, range 19
      91) were sealed under moderate sedation bronchoscopically by either AD (n = 19)
      or AVP (n = 12). The average follow-up period was 17.6 months (range 1-68
      months). RESULTS: The main etiology for BPF was surgery (n = 24), pneumonectomy
      (n = 14) or lobectomy/segmentectomy (n = 10). The underlying disease was either
      primary (n = 19) or metastatic (n = 2) lung cancer. The immediate success rate
      was 96% as symptoms related to BPF disappeared in 30 of the 31 patients. Short
      term (<30 days) mortality was 13% (4 patients). At follow-up, 14 patients (45%)
      are still alive. Out of 12 patients with late mortality, in 5 patients (41%) the
      death was directly related to cancer relapse, and no patient died due to BPF
      recurrence. CONCLUSION: Endobronchial closure of BPF using both types of
      Amplatzer occluders (AD and AVP) is a minimally invasive effective modality of
      treatment with high safety profile and satisfactory long-term outcome considering
      the poor prognosis in this particular group of patients.

PMID- 24434611
TI  - Convergently-evolved structural anomalies in the coiled coil domains of insect
      silk proteins.
AB  - The use of coiled coil proteins as the basis of silk materials is an engineering
      solution that has evolved convergently in at least five insect lineages-the
      stinging hymenopterans (ants, bees, hornets), argid sawflies, fleas, lacewings,
      and praying mantises-and persisted throughout large radiations of these insect
      families. These coiled coil silk proteins share a characteristic distinct from
      other coiled coil proteins, in that they are fabricated into solid materials
      after accumulating as highly concentrated solutions within dedicated glands.
      Here, we relate the amino acid sequences of these proteins to the secondary and
      tertiary structural information available from biophysical methods such as X-ray
      scattering, nuclear magnetic resonance and Raman spectroscopy. We investigate
      conserved and convergently evolved features within these proteins and compare
      these to the features of classic coiled coil proteins including tropomyosin and
      leucine zippers. Our analysis finds that the coiled coil domains of insect silk
      proteins have several common structural anomalies including a high prevalence of
      alanine residues in core positions. These atypical features of the coiled coil
      fibrous proteins - which likely produce deviations from canonical coiled-coil
      structure - likely exist due to selection pressures related to the process of
      silk fabrication and the final function of the proteins. 

PMID- 24434613
TI  - Myeloma in scar tissue--an underreported phenomenon or an emerging entity in the
      novel agents' era? A single center series.
AB  - Tumor relapse in scar tissue is uncommon in cancer patients. Likewise,
      extramedullary plasmacytoma (EMP) relapse in scar tissue in the setting of
      multiple myeloma (MM) has been rarely reported. We report a series of 3 patients
      whose disease progressed as EMP at the site of a wound from previous invasive
      procedures. All 3 patients were treated for the relapsed disease with different
      treatment modalities, but failed to respond adequately and died several months
      after relapse. At original MM diagnosis, all had advanced-stage disease. They
      were treated with novel agents with or without autologous hematopoietic stem cell
      transplantation and achieved either a complete or very good partial response. We
      suggest that these treatments, which have become the standard of care in MM, may
      permit a predominance of myeloma subclones which are independent of the bone
      marrow microenvironment. These myeloma subclones then gain a survival advantage
      in the active scar-tissue niche, allowing for their uncontrolled proliferation.
      This case series might represent an underreported phenomenon and therefore may
      indicate an emerging and difficult-to-treat disease in the era of targeted
      therapies in MM. Physicians treating MM should be aware of this phenomenon,
      especially when referring their patients for invasive procedures.

PMID- 24434612
TI  - Bacterial collagen-like proteins that form triple-helical structures.
AB  - A large number of collagen-like proteins have been identified in bacteria during
      the past 10years, principally from analysis of genome databases. These bacterial
      collagens share the distinctive Gly-Xaa-Yaa repeating amino acid sequence of
      animal collagens which underlies their unique triple-helical structure. A number
      of the bacterial collagens have been expressed in Escherichia coli, and they all
      adopt a triple-helix conformation. Unlike animal collagens, these bacterial
      proteins do not contain the post-translationally modified amino acid,
      hydroxyproline, which is known to stabilize the triple-helix structure and may
      promote self-assembly. Despite the absence of collagen hydroxylation, the triple
      helix structures of the bacterial collagens studied exhibit a high thermal
      stability of 35-39 degrees C, close to that seen for mammalian collagens. These
      bacterial collagens are readily produced in large quantities by recombinant
      methods, either in the original amino acid sequence or in genetically manipulated
      sequences. This new family of recombinant, easy to modify collagens could provide
      a novel system for investigating structural and functional motifs in animal
      collagens and could also form the basis of new biomedical materials with designed
      structural properties and functions. 

PMID- 24434614
TI  - Monitoring bone strontium intake in osteoporotic females self-supplementing with
      strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.
AB  - Ten female volunteers were recruited as part of the Ryerson and McMaster
      University Strontium (Sr) in Bone Research Study to have their bone Sr levels
      measured as they self-supplemented with Sr supplements of their choice. Of the
      ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non
      invasive bone Sr measurements were performed using an in vivo x-ray fluorescence
      (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger
      and ankle, representing primarily cortical and trabecular bone, respectively. For
      analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV
      was used. Baseline readings, representing natural bone Sr levels were acquired
      since all volunteers had no previous intake of Sr based supplements or
      medications. Once Sr supplements were started, a 24h reading was taken, followed
      by frequent measurements ranging from weekly, biweekly to monthly. The longest
      volunteer participation was 1535days. The mean baseline Sr signal observed for
      the group was 0.42+/-0.13 and 0.39+/-0.07 for the finger and ankle, respectively.
      After 24h, the mean Sr signal rose to 1.43+/-1.12 and 1.17+/-0.51, for the finger
      and ankle, respectively, representing a statistically significant increase
      (p=0.0043 & p=0.000613). Bone Sr levels continued to increase throughout the
      length of the study. However the Sr signal varied widely between the individuals
      such that after three years, the highest Sr signal observed was 28.15+/-0.86 for
      the finger and 26.47+/-1.22 for the ankle in one volunteer compared to 3.15+/
      0.15 and 4.46+/-0.36, for the finger and ankle, respectively in another.
      Furthermore, while it was previously reported by our group, that finger bone Sr
      levels may plateau within two years, these results suggest otherwise, indicating
      that bone Sr levels will continue to rise at both bone sites even after 4years of
      Sr intake. 

PMID- 24434615
TI  - End-stage heart failure non-pharmacological therapy: recent advances in
      pacemakers, pressure monitors, pumps and other devices.
AB  - Heart failure is a common, expensive and fatal condition and yet, until recently,
      there was a paucity of treatment options for patients with end-stage heart
      failure (ESHF), other than pharmacotherapy or heart transplant. Recent advances
      mean there is now an array of non-pharmacological therapies available for such
      patients; two such examples are cardiac resynchronisation therapy (CRT) and
      implantable cardioverter defibrillators (ICDs), which improve pump function,
      symptoms, exercise capacity or reduce the risk of arrhythmic death, respectively.
      Furthermore, prior to transplant or if they are deemed unsuitable, patients now
      have the option of a left ventricular assist device (LVAD) or total artificial
      heart (TAH), where available, before heart transplant needs to be considered. The
      concept of remote monitoring is increasingly popular, and while recording
      parameters such as blood pressure and weight are not new, what is new is how
      implantable remote monitoring devices are now able to detect clinical
      decompensation before even the patient is symptomatic and relay this information
      onto the clinician. Other more novel therapies for ESHF include nerve stimulators
      to reduce sympathetic tone, the risk of arrhythmia and augment reverse cardiac
      remodelling and, perhaps the most novel of all, cardiac contractility modulation,
      stimulating the heart paradoxically during the absolute refractory period that
      serves to improve cardiac contractility. 

PMID- 24434616
TI  - Assessment of toxicological effects of blood microsampling in the vehicle dosed
      adult rat.
AB  - Historically, satellite groups are often used for rodent toxicokinetic profiling
      because of the haematological consequences of blood sampling. If microsampling is
      shown to be toxicologically benign, its adoption in rat studies would enable
      comparison of exposure and toxicity in individual animals (as happens in non
      rodent studies) as well as obviating need for satellite groups. METHODS: Groups
      of 10 male (200-300g) and female (150-250g) rats aged 10weeks were vehicle dosed
      and either left unsampled, conventional blood volume sampled (6*200MUL) or
      microsampled (6*32MUL) on Days 1 and 14. At termination on Day 15, clinical
      pathology plus liver and spleen weights and histopathology were obtained.
      RESULTS: All clinical pathology parameters were within background range. However,
      compared to unsampled controls, conventional volume sampled rats showed a
      statistically significant (p<0.001) decrease in haemaglobin, haematocrit and red
      blood cell count, an increase in reticulocytes (at least p<0.01), increased AST
      and GLDH and, in males only, an increase in monocytes and neutrophils. In
      contrast, microsampled animals showed no changes except for a slight,
      toxicologically insignificant decrease in haemoglobin concentration (15.0g/dL
      compared to the unsampled group mean of 14.4g/dL) in females (p<0.05) and a small
      increase in monocytes (p<0.05) in males. CONCLUSION: Microsampling of adult rats
      is possible without adverse toxicological consequences.

PMID- 24434618
TI  - Surface Plasmon Resonance imaging: a method to measure the affinity of the
      antibodies in allergy diagnosis.
AB  - AIM: The biological diagnosis of type I hypersensitivity reactions is based on
      the quantification of specific IgEs. However, the IgE titer is not always
      strongly related to the clinical symptoms or predictive of the evolution of the
      disease. The specificity and affinity of antibodies of other isotypes may
      contribute to the allergic status of the patients. The aim of the present work
      was to develop a method that simultaneously detects the complex antibody response
      to various allergens and measures the avidity of the antibodies directed to each
      allergen. METHODS: A chip based on a covalent binding of 3 major milk allergens
      on a gold-activated surface was developed. The binding of specific antibodies to
      alpha-lactalbumin, beta-lactoglobulin or caseins was monitored using Surface
      Plasmon Resonance imaging (SPRi). The sensitivity and specificity of the method
      were compared to those obtained by ELISA, the reference method. RESULTS: The
      specificity of the antibodies characterized by SPRi was identical to the one
      obtained by ELISA. The intensity of the signal was proportional to the quantity
      of antibodies bound to each allergen. The sensitivity of the SPRi detection was
      about 8-10 times lower than for ELISA but the SPRi is faster and the analysis of
      association/dissociation kinetics allowed the determination of the avidity of the
      antibody response. CONCLUSION: The present study shows that SPRi allows a
      multiplex monitoring of the complex antibody response to the major allergens of
      an allergenic source. This label-free method constitutes a new tool that may be
      added to IgE detection to improve allergy diagnosis.

PMID- 24434619
TI  - In vitro phosphorylation does not influence the aggregation kinetics of WT alpha
      synuclein in contrast to its phosphorylation mutants.
AB  - The aggregation of alpha-synuclein (alpha-SYN) into fibrils is characteristic for
      several neurodegenerative diseases, including Parkinson's disease (PD). Ninety
      percent of alpha-SYN deposited in Lewy Bodies, a pathological hallmark of PD, is
      phosphorylated on serine129. alpha-SYN can also be phosphorylated on tyrosine125,
      which is believed to regulate the membrane binding capacity and thus possibly its
      normal function. A better understanding of the effect of phosphorylation on the
      aggregation of alpha-SYN might shed light on its role in the pathogenesis of PD.
      In this study we compare the aggregation properties of WT alpha-SYN with the
      phospho-dead and phospho-mimic mutants S129A, S129D, Y125F and Y125E and in vitro
      phosphorylated alpha-SYN using turbidity, thioflavin T and circular dichroism
      measurements as well as transmission electron microscopy. We show that the
      mutants S129A and S129D behave similarly compared to wild type (WT) alpha-SYN,
      while the mutants Y125F and Y125E fibrillate significantly slower, although all
      mutants form fibrillar structures similar to the WT protein. In contrast, in
      vitro phosphorylation of alpha-SYN on either S129 or Y125 does not significantly
      affect the fibrillization kinetics. Moreover, FK506 binding proteins (FKBPs),
      enzymes with peptidyl-prolyl cis-trans isomerase activity, still accelerate the
      aggregation of phosphorylated alpha-SYN in vitro, as was shown previously for WT
      alpha-SYN. In conclusion, our results illustrate that phosphorylation mutants can
      display different aggregation properties compared to the more biologically
      relevant phosphorylated form of alpha-SYN. 

PMID- 24434620
TI  - Identification of the high molecular weight isoform of phostensin.
AB  - Phostensin is encoded by KIAA1949. 5'-RACEanalysis has been used to identify the
      translation start site of phostensin mRNA, indicating that it encodes 165 amino
      acids with an apparent molecular weight of 26 kDa on SDS-PAGE. This low-molecular
      weight phostensin is present in human peripheral blood mononuclear cells and many
      leukemic cell lines. Phostensin is a protein phosphatase-1(PP1) binding protein.
      It also contains one actin-binding motif at its C-terminal region and binds to
      the pointed ends of actin filaments, modulating actin dynamics. In the current
      study, a high-molecular-weight phostensin is identified by using
      immunoprecipitationin combination with a proteomic approach. This new species of
      phostensin is also encoded by KIAA1949 and consists of 613 amino acids with an
      apparent molecular weight of 110 kDa on SDS-PAGE. The low-molecular-weight and
      high-molecular-weight phostensins were named as phostensin-alpha and phostensin
      beta, respectively. Although phostensin-alpha is the C-terminal region of
      phostensin-beta, it is not degraded from phostensin-beta. Phostensin-beta is
      capable of associating with PP1 and actin filaments, and is present in many cell
      lines. 

PMID- 24434622
TI  - Respiratory motion guided four dimensional cone beam computed tomography:
      encompassing irregular breathing.
AB  - Four dimensional cone beam computed tomography (4DCBCT) images suffer from
      angular under sampling and bunching of projections due to a lack of feedback
      between the respiratory signal and the acquisition system. To address this
      problem, respiratory motion guided 4DCBCT (RMG-4DCBCT) regulates the gantry
      velocity and projection time interval, in response to the patient's respiratory
      signal, with the aim of acquiring evenly spaced projections in a number of phase
      or displacement bins during the respiratory cycle. Our previous study of RMG
      4DCBCT was limited to sinusoidal breathing traces. Here we expand on that work to
      provide a practical algorithm for the case of real patient breathing data. We
      give a complete description of RMG-4DCBCT including full details on how to
      implement the algorithms to determine when to move the gantry and when to acquire
      projections in response to the patient's respiratory signal. We simulate a
      realistic working RMG-4DCBCT system using 112 breathing traces from 24 lung
      cancer patients. Acquisition used phase-based binning and parameter settings
      typically used on commercial 4DCBCT systems (4 min acquisition time, 1200
      projections across 10 respiratory bins), with the acceleration and velocity
      constraints of current generation linear accelerators. We quantified streaking
      artefacts and image noise for conventional and RMG-4DCBCT methods by
      reconstructing projection data selected from an oversampled set of Catphan
      phantom projections. RMG-4DCBCT allows us to optimally trade-off image quality,
      acquisition time and image dose. For example, for the same image quality and
      acquisition time as conventional 4DCBCT approximately half the imaging dose is
      needed. Alternatively, for the same imaging dose, the image quality as measured
      by the signal to noise ratio, is improved by 63% on average. C-arm cone beam
      computed tomography systems, with an acceleration up to 200 degrees /s(2), a
      velocity up to 100 degrees /s and the acquisition of 80 projections per second,
      allow the image acquisition time to be reduced to below 60 s. We have made
      considerable progress towards realizing a system to reduce projection clustering
      in conventional 4DCBCT imaging and hence reduce the imaging dose to the patient. 

PMID- 24434621
TI  - The function and catalysis of 2-oxoglutarate-dependent oxygenases involved in
      plant flavonoid biosynthesis.
AB  - Flavonoids are secondary metabolites derived from phenylalanine and acetate
      metabolism. They fulfil a variety of functions in plants and have health benefits
      for humans. During the synthesis of the tricyclic flavonoid natural products in
      plants, oxidative modifications to the central C ring are catalyzed by four of
      FeII and 2-oxoglutarate dependent (2-ODD) oxygenases, namely flavone synthase I
      (FNS I), flavonol synthase (FLS), anthocyanidin synthase (ANS) and flavanone
      3beta-hydroxylase (FHT). FNS I, FLS and ANS are involved in desaturation of C2-C3
      of flavonoids and FHT in hydroxylation of C3. FNS I, which is restricted to the
      Apiaceae species and in rice, is predicted to have evolved from FHT by
      duplication. Due to their sequence similarity and substrate specificity, FLS and
      ANS, which interact with the alpha surface of the substrate, belong to a group of
      dioxygenases having a broad substrate specificity, while FNS I and FHT are more
      selective, and interact with the naringenin beta surface. Here, we summarize
      recent findings regarding the function of the four 2-ODD oxygenases and the
      relationship between their catalytic activity, their polypeptide sequence and
      their tertiary structure. 

PMID- 24434623
TI  - Meta-analysis of lipid-lowering therapy in maintenance dialysis patients.
AB  - BACKGROUND/AIMS: The use of lipid-lowering therapy (LLT) in patients on chronic
      dialysis is contentious. Here we present an aggregate data meta-analysis of
      randomised controlled trials (RCTs) comparing long-term LLT versus placebo in
      dialysis patients. METHOD: A search of Medline, Google Scholar, COCHRANE
      database, EMBASE, and cardiovascular and nephrology society proceedings was
      performed. Criteria for inclusion were RCTs of LLT versus placebo, in which LLT
      was demonstrated to significantly reduce low-density lipoprotein cholesterol, >12
      months of follow-up, and at least one cardiovascular or mortality endpoint in an
      independently reported dialysis population. Meta-analysis was performed for
      atherosclerotic cardiovascular events, stroke and mortality using a random
      effects method for odds ratio (OR) of risk. RESULTS: Three studies were included
      with 7,051 patients (3,541 treatment and 3,510 placebo). Twenty-five percent of
      the LLT patients suffered an atherosclerotic cardiovascular event versus 27% for
      placebo. The OR was 0.89 (95% CI: 0.80-0.99, p = 0.04). For stroke (haemorrhagic
      and non-haemorrhagic combined), the figures were 6.2% (LLT) versus 5.7% (placebo)
      [OR = 1.11 (95% CI: 0.85-1.46, p = 0.45)]. For all-cause mortality, the figures
      were 40 versus 42% [OR = 0.97 (95% CI: 0.88-1.06, p = 0.49)]. CONCLUSION: There
      was an overall significant reduction in risk for atherosclerotic cardiovascular
      events in dialysis patients treated with LLT compared to placebo. There was a
      numerical but not a statistical reduction in mortality. There was no
      statistically significant increase in risk of stroke as has been previously
      reported.

PMID- 24434624
TI  - Electroencephalographic upper/low alpha frequency power ratio relates to cortex
      thinning in mild cognitive impairment.
AB  - OBJECTIVE: Temporoparietal cortex thinning is associated with mild cognitive
      impairment (MCI) due to Alzheimer disease (AD). The increase in EEG upper/low
      alpha frequency power ratio has been associated with AD converter MCI subjects.
      We investigated the association of the EEG upper/low alpha frequency power ratio
      with patterns of cortical thickness in MCI. METHODS: 74 adult subjects with MCI
      underwent clinical and neuropsychological evaluation, electroencephalography
      (EEG) recording and high-resolution 3-dimensional magnetic resonance imaging
      (MRI). The EEG upper/low alpha frequency power ratio as well as cortical
      thickness were computed for each subject. Three MCI groups were detected
      according to increasing tertile values of EEG upper/low alpha frequency power
      ratios, and the difference of cortical thickness among the groups was estimated.
      RESULTS: The EEG high upper/low alpha frequency power ratio group had a total
      cortical grey matter volume reduction of 471 mm(2), greater than that of the EEG
      low upper/low alpha frequency power ratio group (p < 0.001). The EEG high
      upper/low alpha frequency power ratio group showed a similar but less marked
      pattern (160 mm(2)) of cortical thinning when compared to the EEG middle
      upper/low alpha frequency power ratio group (p < 0.001). Moreover, the EEG high
      upper/low alpha frequency power ratio group had wider cortical thinning than
      other groups, mapped to the supramarginal gyrus and precuneus bilaterally. No
      significant regional cortical thickness differences were found between middle and
      low EEG upper/low alpha frequency power ratio groups. CONCLUSION: A high EEG
      upper/low alpha frequency power ratio was associated with temporoparietal
      cortical thinning in MCI subjects. The combination of upper/low alpha frequency
      power ratio and cortical thickness measurement could be useful for identifying
      individuals at risk for progression to AD dementia and may be of value in the
      clinical context.

PMID- 24434625
TI  - Effect of torsional stiffness and inertia on the dynamics of low aspect ratio
      flapping wings.
AB  - Micro air vehicle-motivated aerodynamics in biological flight has been an
      important subject in the past decade. Inspired by the novel flapping wing
      mechanisms in insects, birds and bats, we have carried out a numerical study
      systematically investigating a three-dimensional flapping rigid wing with
      passively actuated lateral and rotational motion. Distinguishing it from the
      limited existing studies, this work performs a systematic examination on the
      effects of wing aspect ratio (AR = 1.0 to infinity), inertia (density ratio sigma
      = 4-32), torsional stiffness (frequency ratio F = 1.5-10 and infinity) and pivot
      point (from chord-center to leading edge) on the dynamics response of a low AR
      rectangular wing under an initial zero speed flow field condition. The simulation
      results show that the symmetry breakdown of the flapping wing results in a
      forward/backward motion with a rotational pitching. When the wing reaches its
      stable periodic state, the induced pitching frequency is identical to its forced
      flapping frequency. However, depending on various kinematic and dynamic system
      parameters, (i.e. flapping frequency, density ratio and pitching axis), the
      lateral induced velocity shows a number of different oscillating frequencies.
      Furthermore, compared with a one degree of freedom (DoF) wing in the lateral
      direction only, the propulsion performance of such a two DoF wing relies very
      much on the magnitude of torsional stiffness adding on the pivot point, as well
      as its pitching axis. In all cases examined here, thrust force and moment
      generated by a long span wing is larger than that of a short wing, which is
      remarkably linked to the strong reverse von Karman vortex street formed in the
      wake of a wing. 

PMID- 24434626
TI  - Visual categorization is automatic and obligatory: evidence from Stroop-like
      paradigm.
AB  - Human observers categorize visual stimuli with remarkable efficiency--a result
      that has led to the suggestion that object and scene categorization may be
      automatic processes. We tested this hypothesis by presenting observers with a
      modified Stroop paradigm in which object or scene words were presented over
      images of objects or scenes. Terms were either congruent or incongruent with the
      images. Observers classified the words as being object or scene terms while
      ignoring images. Classifying a word on an incongruent image came at a cost for
      both objects and scenes. Furthermore, automatic processing was observed for entry
      level scene categories, but not superordinate-level categories, suggesting that
      not all rapid categorizations are automatic. Taken together, we have demonstrated
      that entry-level visual categorization is an automatic and obligatory process.

PMID- 24434627
TI  - Adaptation to vergent and averted eye gaze.
AB  - Previous adaptation studies have revealed the tuning properties of mechanisms
      coding left-right averted gaze. Here, Experiment 1 used an adaptation procedure
      to investigate the mechanisms that encode vergent eye gaze. Following prolonged
      exposure to convergent or divergent gaze, observers were more likely to
      categorize smaller gaze deviations in the adapted direction as parallel (i.e.,
      nonvergent). We then examined whether adaptation was occurring to the eyes
      independently (monocular gaze direction) as opposed to the two eyes as a unitary
      stimulus (binocular gaze direction). In Experiment 2, we interleaved
      presentations of convergent and divergent adaptors and tested with either
      congruent (vergent) or incongruent (left-right) stimuli. Similarly, we
      interleaved presentations of leftward- and rightward-averted adaptors and tested
      with congruent (left-right) and incongruent (vergent) stimuli. If adaptation were
      driven solely by monocular gaze direction, congruent and incongruent adaptation
      would be similar because, at the level of an individual eye, the stimuli are
      identical. We find considerable adaptation in the incongruent conditions,
      consistent with adaptation to individual eye directions. However, we also find
      greater adaptation in congruent conditions, implicating the involvement of
      mechanisms that encode binocular gaze direction. 

PMID- 24434628
TI  - The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human
      endothelial cells and osteoblasts: implications for arthritic joints.
AB  - This study was performed to evaluate the contribution of adiponectin to the
      production of interleukin (IL)-6, IL-8, vascular endothelial growth factor
      (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells
      and osteoblasts in arthritic joints. Cultured human umbilical vascular
      endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or
      10 MUg ml(-1)) or IL-1beta (0.1 ng ml(-1)) in the presence or absence of hypoxia
      for 24 h. The protein expression patterns were examined by analyzing culture
      supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin
      significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts
      but not in endothelial cells, whereas it significantly stimulated the production
      of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF
      production induced by adiponectin was significantly greater than that induced by
      IL-1beta. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial
      cells was approximately 10-fold higher than that in IL-1beta-stimulated
      endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion
      was approximately twofold higher than that induced by IL-1beta. In addition, IL-8
      production in endothelial cells was approximately sevenfold higher than in
      osteoblasts. However, IL-6 levels were similar between the two cell types,
      suggesting that adiponectin may be involved in the production of IL-8 in
      endothelial cells, which may have an important role in neutrophil recruitment to
      arthritic joints. Furthermore, the increases in protein expression induced by
      adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin
      has a more important role than does IL-1beta in the production of mediators that
      drive synovitis and joint destruction in endothelial cells and osteoblasts at
      physiological concentrations. 

PMID- 24434630
TI  - 2-Bromopalmitate modulates neuronal differentiation through the regulation of
      histone acetylation.
AB  - In order to evaluate the functional significance of palmitoylation during multi
      potent neural stem/progenitor cell proliferation and differentiation, retinoic
      acid-induced P19 cells were used in this study as a model system. Cell behaviour
      was monitored in the presence of the protein palmitoylation inhibitor 2
      bromopalmitate (2BP). Here, we observed a significant reduction in neuronal
      differentiation in the 2BP-treated cell model. We further explored the underlying
      mechanisms and found that 2BP resulted in the decreased acetylation of histones
      H3 and H4 and interfered with cell cycle withdrawal and neural stem/progenitor
      cells' renewal. Our results established a direct link between palmitoylation and
      the regulation of neural cell fate specification and revealed the epigenetic
      regulatory mechanisms that are involved in the effects of palmitoylation during
      neural development. 

PMID- 24434629
TI  - Dystrophin-deficient cardiomyocytes derived from human urine: new biologic
      reagents for drug discovery.
AB  - The ability to extract somatic cells from a patient and reprogram them to
      pluripotency opens up new possibilities for personalized medicine. Induced
      pluripotent stem cells (iPSCs) have been employed to generate beating
      cardiomyocytes from a patient's skin or blood cells. Here, iPSC methods were used
      to generate cardiomyocytes starting from the urine of a patient with Duchenne
      muscular dystrophy (DMD). Urine was chosen as a starting material because it
      contains adult stem cells called urine-derived stem cells (USCs). USCs express
      the canonical reprogramming factors c-myc and klf4, and possess high telomerase
      activity. Pluripotency of urine-derived iPSC clones was confirmed by
      immunocytochemistry, RT-PCR and teratoma formation. Urine-derived iPSC clones
      generated from healthy volunteers and a DMD patient were differentiated into
      beating cardiomyocytes using a series of small molecules in monolayer culture.
      Results indicate that cardiomyocytes retain the DMD patient's dystrophin
      mutation. Physiological assays suggest that dystrophin-deficient cardiomyocytes
      possess phenotypic differences from normal cardiomyocytes. These results
      demonstrate the feasibility of generating cardiomyocytes from a urine sample and
      that urine-derived cardiomyocytes retain characteristic features that might be
      further exploited for mechanistic studies and drug discovery. 

PMID- 24434631
TI  - Perlecan is required for FGF-2 signaling in the neural stem cell niche.
AB  - In the adult subventricular zone (neurogenic niche), neural stem cells double
      positive for two markers of subsets of neural stem cells in the adult central
      nervous system, glial fibrillary acidic protein and CD133, lie in proximity to
      fractones and to blood vessel basement membranes, which contain the heparan
      sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency
      reduces the number of both GFAP/CD133-positive neural stem cells in the
      subventricular zone and new neurons integrating into the olfactory bulb. We also
      show that FGF-2 treatment induces the expression of cyclin D2 through the
      activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in
      vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere
      formation. These results suggest that perlecan is a component of the neurogenic
      niche that regulates FGF-2 signaling and acts by promoting neural stem cell self
      renewal and neurogenesis. 

PMID- 24434633
TI  - Laboratory investigation of platelet function in patients with thalassaemia.
AB  - The aim of this study was to investigate platelet function in patients with
      thalassaemia and to detect any relation to chelation treatment (deferasirox or
      deferiprone/deferiprone plus desferioxamine). Thirty-three transfusion-dependent
      patients with thalassaemia were included. The investigation consisted of
      aggregation testing of platelet-rich plasma by light transmission aggregometry
      (LTA) with the use of 5 agonists as well as the global test of haemostasis by
      means of the PFA-100 platelet function analyser. In 66.67% of the patients, there
      was reduced LTA to at least one agonist and in 18.18% there was reduced LTA to
      two or more agonists. The PFA-100 test was prolonged in 60.6% of the cases. An
      abnormal LTA and a prolonged PFA-100 time were recorded in 33.3% of the patients
      and 27.4% had a normal aggregation and PFA-100 test. No correlation between
      chelation regimen and either LTA or PFA-100 test was found. The abnormal LTA can
      be explained either by the release of ADP from the haemolysed red blood cells,
      which leads to defective platelet aggregation, or by the presence of two platelet
      populations. An in vitro effect without an in vivo impact could be an alternative
      explanation. In patients with thalassaemia, the reduced LTA and the prolonged PFA
      100 closure time could be an in vitro effect and has a close correlation to the
      bleeding phenotype of each patient.

PMID- 24434634
TI  - The role of systemic therapies in the management of melanoma brain metastases.
AB  - PURPOSE OF REVIEW: Brain metastases in metastatic melanoma are highly prevalent
      and are associated with significant morbidity and a poor prognosis. Local therapy
      (surgery or radiotherapy) has been the mainstay of treatment, due in part to the
      lack of efficacy of systemic therapy. This review will focus on new systemic
      therapies for metastatic melanoma and their evolving role in the management of
      brain metastases. RECENT FINDINGS: BRAF inhibitors have demonstrated efficacy in
      active (i.e. untreated or progressing) brain metastases in BRAF mutated
      metastatic melanoma. The cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody,
      ipilimumab, has also shown activity, particularly in asymptomatic metastases.
      Studies of programmed death 1/programmed death ligand 1 checkpoint inhibitors and
      combination BRAF and MEK inhibitor therapy in brain metastases are planned.
      Emerging evidence on the molecular biology of melanoma brain metastases,
      particularly the role of the phosphatidylinositol 3-kinase-AKT pathway, may
      identify additional therapeutic targets. SUMMARY: The development of systemic
      therapy effective in controlling both intra-cranial and extra-cranial melanoma
      metastases has resulted in a change in the paradigm of management. More research
      is required in patients with active brain metastases to improve patient outcomes,
      including studies early in the development of novel therapies, and studies to
      determine the safe and effective combination or sequencing of local and systemic
      therapies.

PMID- 24434632
TI  - Comparing protein folding in vitro and in vivo: foldability meets the fitness
      challenge.
AB  - In this review, we compare and contrast current knowledge about in vitro and in
      vivo protein folding. Major advances in understanding fundamental principles
      underlying protein folding in optimized in vitro conditions have yielded detailed
      physicochemical principles of folding landscapes for small, single domain
      proteins. In addition, there has been increased research focusing on the key
      features of protein folding in the cell that differentiate it from in vitro
      folding, such as co-translational folding, chaperone-facilitated folding, and
      folding in crowded conditions with many weak interactions. Yet these two research
      areas have not been bridged effectively in research carried out to date. This
      review points to gaps between the two that are ripe for future research.
      Moreover, we emphasize the biological selection pressures that impact protein
      folding in vivo and how fitness drives the evolution of protein sequences in ways
      that may place foldability in tension with other requirements on a given protein.
      We suggest that viewing the physicochemical process of protein folding through
      the lens of evolution will unveil new insights and pose novel challenges about in
      cell folding landscapes. 

PMID- 24434635
TI  - Nematode-derived drosomycin-type antifungal peptides provide evidence for plant
      to-ecdysozoan horizontal transfer of a disease resistance gene.
AB  - Drosomycin-type antifungal peptides (DTAFPs) are key innate immunity components
      of Drosophila and plants and confer resistance to fungal infection. Here we
      report the discovery of a multigene family of DTAFPs, comprising of 15 members
      (termed cremycin-1 to crymycin-15), in the fruit nematode Caenorhabditis remanei.
      Cremycins share highly similar amino-acid sequences and identical precursor
      organization to drosomycins. Of the 15 cremycin genes, 10 are found to be
      transcriptionally active and 6 are upregulated after fungal challenge. Synthetic
      cremycin-5 is active on filamentous fungi and a series of clinical isolates of
      human pathogenic yeasts and exhibits low haemolysis and high serum stability. The
      specific distribution of DTAFPs in a clade of moulting animals (Ecdysozoa),
      including Arthropoda, Nematoda and Tardigrada, together with the widespread
      presence in plants but the absence in fungi and protozoans, provides evidence for
      horizontal transfer of a disease resistance gene between plants and ecdysozoans. 

PMID- 24434636
TI  - Sphingosine-1-phosphate differently regulates the cytokine production of IL-12,
      IL-23 and IL-27 in activated murine bone marrow derived dendritic cells.
AB  - Sphingosine-1-phosphate (S1P) modulates many cell functions such as lymphocyte
      trafficking and signaling as well as keratinocyte proliferation. However, less is
      known about the specific effects of S1P on cytokine production, particularly on
      the interaction between dendritic cells (DCs) and keratinocytes, cell types which
      are crucial for the initiation and maintenance of chronic inflammatory skin
      diseases like atopic dermatitis or psoriasis. Especially the cytokines of the IL
      12 family play a dominant role in many inflammatory diseases as they have a
      significant impact on T-helper cell function. In the present study we show that
      S1P decreased the production of the pro-inflammatory cytokines IL-12 and IL-23 in
      LPS-stimulated DCs via the common subunit p40 as well as in the crosstalk with
      activated keratinocytes. By using specific S1P receptor agonists (SEW2871, FTY720
      P) and antagonist (JTE013) we identified an important role for S1P receptor 1 in
      the modulation of the cytokine profile. While diminishing IL-12 and IL-23
      secretion, S1P enhanced IL-27 production in DCs. To elucidate the mechanism of
      the different impact on the IL-12 family cytokine production, we investigated the
      mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)
      pathways in DCs. By using specific MAPK-Inhibitors (U0126, SB202190, SP600125) we
      demonstrated that ERK, p38 and JNK differently regulate each pathway of each
      cytokine. While p38 and JNK did not seem to play a role in the modulation
      properties of S1P on cytokine production, ERK is at least partially involved in
      the S1P mediated modulation of IL-12 and IL-27. The PI3K-Inhibitor abrogated the
      S1P-induced decrease of IL-12 and IL-23 secretion, while it had no influence on
      the S1P-induced increase of IL-27 production. These data implicate, that S1P has
      an anti-inflammatory impact on the production of IL-12 family cytokines,
      indicating therapeutic potential for S1P treatment of several inflammatory
      diseases like psoriasis. 

PMID- 24434637
TI  - Aldehyde dehydrogenase 2 ameliorates doxorubicin-induced myocardial dysfunction
      through detoxification of 4-HNE and suppression of autophagy.
AB  - Mitochondrial aldehyde dehydrogenase (ALDH2) protects against cardiac injury via
      reducing production of 4-hydroxynonenal (4-HNE) and ROS. This study was designed
      to examine the impact of ALDH2 on doxorubicin (DOX)-induced cardiomyopathy and
      mechanisms involved with a focus on autophagy. 4-HNE and autophagic markers were
      detected by Western blotting in ventricular tissues from normal donors and
      patients with idiopathic dilated cardiomyopathy. Cardiac function, 4-HNE and
      levels of autophagic markers were detected in WT, ALDH2 knockout or ALDH2
      transfected mice treated with or without DOX. Autophagy regulatory signaling
      including PI-3K, AMPK and Akt was examined in DOX-treated cardiomyocytes
      incubated with or without ALDH2 activator Alda-1. DOX-induced myocardial
      dysfunction, upregulation of 4-HNE and autophagic proteins were further
      aggravated in ALDH2 knockout mice while they were ameliorated in ALDH2
      transfected mice. DOX downregulated Class I and upregulated Class III PI3-kinase,
      the effect of which was augmented by ALDH2 deletion. Accumulation of 4-HNE and
      autophagic protein markers in DOX-induced cardiomyocytes was significantly
      reduced by Alda-1. DOX depressed phosphorylated Akt but not AMPK, the effect was
      augmented by ALDH2 knockout. The autophagy inhibitor 3-MA attenuated, whereas
      autophagy inducer rapamycin mimicked DOX-induced cardiomyocyte contractile
      defects. In addition, rapamycin effectively mitigated Alda-1-offered protective
      action against DOX-induced cardiomyocyte dysfunction. Our data further revealed
      downregulated ALDH2 and upregulated autophagy levels in the hearts from patients
      with dilated cardiomyopathy. Taken together, our findings suggest that inhibition
      of 4-HNE and autophagy may be a plausible mechanism underscoring ALDH2-offered
      protection against DOX-induced cardiac defect. This article is part of a Special
      Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and
      Autophagy". 

PMID- 24434638
TI  - The effect of radiation on the immune response to cancers.
AB  - In cancer patients undergoing radiation therapy, the beneficial effects of
      radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of
      localized radiation to tumors often leads to systemic responses at distant sites,
      a phenomenon known as the abscopal effect which has been attributed to the
      induction and enhancement of the endogenous anti-tumor innate and adaptive immune
      response. The mechanisms surrounding the abscopal effect are diverse and include
      trafficking of lymphocytes into the tumor microenvironment, enhanced tumor
      recognition and killing via up-regulation of tumor antigens and antigen
      presenting machinery and, induction of positive immunomodulatory pathways. Here,
      we discuss potential mechanisms of radiation-induced enhancement of the anti
      tumor response through its effect on the host immune system and explore potential
      combinational immune-based strategies such as adoptive cellular therapy using ex
      vivo expanded NK and T cells as a means of delivering a potent effector
      population in the context of radiation-enhanced anti-tumor immune environment. 

PMID- 24434639
TI  - Purification and characterization of iso-ribonucleases from a novel thermophilic
      fungus.
AB  - A thermophilic fungus previously isolated from composted horse manure was found
      to produce extracellular iso-RNases that were purified 127.6-fold using a
      combination of size exclusion chromatography and a novel affinity membrane
      purification system. The extent of purification was determined
      electrophoretically using 4%-15% gradient polyacrylamide gels. RNase activity was
      dependent on the presence of a metal co-factor with significantly more activity
      with Zn2+ or Mn2+ than Mg2+. The RNases exhibited maximum activity at both pH 3.0
      and pH 7.0 with no activity at pH 2.0 or 10.0. The optimal temperature for the
      iso-RNase was 70  degrees C. The molecular weight of the iso-RNase was determined
      to be 69 kDa using a Sephadex G-75 column. 

PMID- 24434640
TI  - Genistein induces increase in fluid pH, Na+ and HCO3(-) concentration, SLC26A6
      and SLC4A4 (NBCe1)-B expression in the uteri of ovariectomized rats.
AB  - Genistein has been reported to stimulate luminal HCO3(-) secretion. We
      hypothesized that genistein mediates this effect via SLC26A6 and SLC4A4 (NBCe1)
      transporters. Our study aimed to: investigate changes in uterine fluid pH, Na+
      and HCO3(-) concentration and expression of uterine SLC26A6 and NBCe1 under
      genistein effect. Ovariectomized adult female rats received 25, 50 and 100
      mg/kg/day genistein for a week with and without ICI 182780. A day after the last
      injection, in vivo uterine perfusion was performed to collect uterine fluid for
      Na+, HCO3(-) and pH determination. The animals were then sacrificed and uteri
      were removed for mRNA and protein expression analyses. SLC26A6 and NBCe1-A and
      NBCe1-B distribution were visualized by immunohistochemistry (IHC). Genistein at
      50 and 100 mg/kg/day stimulates uterine fluid pH, Na+ and HCO3(-) concentration
      increase. Genistein at 100 mg/kg/day up-regulates the expression of SLC26A6 and
      SLC4A4 mRNA, which were reduced following concomitant ICI 182780 administration.
      In parallel, SLC26A6 and NBCe1-B protein expression were also increased following
      high dose genistein treatment and were localized mainly at the apical membrane of
      the luminal epithelia. SLC26A6 and NBCe1-B up-regulation by genistein could be
      responsible for the observed increase in the uterine fluid pH, Na+ and HCO3(-)
      concentration under this condition.

PMID- 24434641
TI  - Serum starvation-induced voltage-gated potassium channel Kv7.5 expression and its
      regulation by Sp1 in canine osteosarcoma cells.
AB  - The KCNQ gene family, whose members encode Kv7 channels, belongs to the voltage
      gated potassium (Kv) channel group. The roles of this gene family have been
      widely investigated in nerve and muscle cells. In the present study, we
      investigated several characteristics of Kv7.5, which is strongly expressed in the
      canine osteosarcoma cell line, CCL-183. Serum starvation upregulated Kv7.5
      expression, and the Kv7 channel opener, flupirtine, attenuated cell proliferation
      by arresting cells in the G0/G1 phase. We also showed that Kv7.5 knockdown helps
      CCL-183 cells to proliferate. In an effort to find an endogenous regulator of
      Kv7.5, we used mithramycin A to reduce the level of the transcription factor Sp1,
      and it strongly inhibited the induction of Kv7.5 in CCL-183 cells. These results
      suggest that the activation of Kv7.5 by flupirtine may exert an anti
      proliferative effect in canine osteosarcoma. Therefore, Kv7.5 is a possible
      molecular target for canine osteosarcoma therapy. 

PMID- 24434642
TI  - Walnuts (seeds of Juglandis sinensis L.) protect human epidermal keratinocytes
      against UVB-induced mitochondria-mediated apoptosis through upregulation of ROS
      elimination pathways.
AB  - PURPOSE: Ultraviolet (UV) light from sunlight is an important environmental
      factor causing hazardous health effects, including various skin disorders. UV
      irradiation downregulates reactive oxygen species (ROS) elimination pathways,
      thereby promoting the production of ROS, which are implicated in mitochondria
      mediated apoptosis. Walnuts, the seeds of Juglandis sinensis L., are a highly
      nutritious food and have been shown to have a number of pharmacological
      activities. To our knowledge, no study on the protective effects of walnuts on
      human epidermal keratinocytes has been reported previously. Here, we investigated
      the protective effects of walnuts against UVB (50 mJ/cm(2)) -induced mitochondria
      mediated apoptosis. PROCEDURES AND RESULTS: Walnuts significantly and dose
      dependently reduced UVB-induced apoptotic toxicity by lactate dehydrogenase assay
      kit. Walnuts decreased mitochondrial dysfunction, B-cell lymphoma 2 (Bcl-2)
      associated X (Bax) protein levels, and cytochrome c release from mitochondria,
      while increasing Bcl-2 protein levels using immunofluorescence, Western blot, or
      kit analysis. Moreover, walnuts inhibited caspase-3 activity, indicating an
      inhibition of the apoptotic cascade, and induced the expression of heme oxygenase
      and NAD(P)H dehydrogenase via NF-E2-related factor-2 activation using
      immunofluorescence or Western blot analysis. CONCLUSION: Together, these results
      demonstrate that walnuts can protect human epidermal keratinocytes against UVB
      induced mitochondria-mediated apoptosis by regulating ROS elimination pathways.

PMID- 24434643
TI  - Ischemic preconditioning protects cardiomyocyte mitochondria through mechanisms
      independent of cytosol.
AB  - Mitochondria play a central role in the protection conferred by ischemic
      preconditioning (IP) by not fully elucidated mechanisms. We investigated whether
      IP protects mitochondria against ischemia-reperfusion (IR) injury through
      mechanisms independent of cytosolic signaling. In isolated rat hearts, sublethal
      IR increased superoxide production and reduced complex-I- and II-mediated
      respiration in subsarcolemmal (SS), but not interfibrillar (IF) mitochondria.
      This effect of IR on mitochondrial respiration was significantly attenuated by
      IP. Similar results were obtained in isolated cardiac mitochondria subjected to
      in vitro IR. The reduction in SS mitochondrial respiration in the heart and in
      vitro model was paralleled by an increase in oxidized cysteine residues, which
      was also prevented by IP. IP was also protective in mitochondria submitted to
      lethal IR. The protective effect of IP against respiratory failure was unaffected
      by inhibition of mitochondrial KATP channels or mitochondrial permeability
      transition. However, IP protection was lost in mitochondria from genetically
      modified animals in which connexin-43, a protein present in SS but not IF
      mitochondria, was replaced by connexin-32. Our results demonstrate the existence
      of a protective mitochondrial mechanism or "mitochondrial preconditioning"
      independent of cytosol that confers protection against IR-induced respiratory
      failure and oxidative damage, and requires connexin-43. 

PMID- 24434644
TI  - Percutaneous transhepatic biliary drainage in patients with postsurgical bile
      leakage and nondilated intrahepatic bile ducts.
AB  - OBJECTIVE AND BACKGROUND: Bile leakage is a serious postoperative complication
      and percutaneous transhepatic biliary drainage (PTBD) may be an option when
      endoscopic treatment is not feasible. In this retrospective study, we established
      technical and clinical success rates as well as the complication rates of PTBD in
      a large group of patients with postoperative bile leakage. METHODS: Data on all
      patients with nondilated intrahepatic bile ducts who underwent a PTBD procedure
      for the treatment of bile leakage between January 2000 and August 2012 were
      retrospectively assessed. Data included type of surgery, site of bile leak,
      previous attempts of bile leak repair, interval between surgery and PTBD
      placement. Outcome measures were the technical and clinical success rates, the
      procedure-related complications, and mortality rate. RESULTS: A total of 63
      patients were identified; PTBD placement was technically successful in 90.5%
      (57/63) after one to three attempts. The clinical success rate was 69.8% (44/63).
      Four major complications were documented (4/63; 6.3%): liver laceration,
      pneumothorax, pleural empyema, and prolonged hemobilia. One minor complication
      involved pain. CONCLUSIONS: PTBD is an effective treatment with low complication
      rates for the management of postsurgical bile leaks in patients with nondilated
      bile ducts.

PMID- 24434646
TI  - Genomic organization and functional diversification of two warm-temperature
      acclimation-associated 65-kDa protein genes in rockbream (Oplegnathus fasciatus;
      Perciformes).
AB  - Two paralogue genes of warm-temperature-acclimation-associated 65-kDa protein
      were characterized and their mRNA expression patterns during various experimental
      stimulations were examined in the rockbream (Oplegnathus fasciatus; Perciformes).
      Rockbream Wap65 isoforms (rbWap65-1 and rbWap65-2) share basically common
      structural features with other teleostean orthologues and human hemopexin (HPX)
      at both amino acid (conserved cysteine and histidine residues) and genomic levels
      (ten-exon structure), although the rbWap65-2 reveals more homologous
      characteristics to human HPX than does rbWap65-1 isoform. Southern blot analysis
      indicates that each rbWap65 isoform exists as a single copy gene in the rockbream
      genome. Both rbWap65 genes were predicted to possess various transcription factor
      (TF) binding motifs related with stress and innate immunity in their 5'-upstream
      regions, in which inflammation-related motifs were more highlighted in the
      rbWap65-2 than in rbWap65-1. Based on the RT-PCR assay, the liver-predominant
      expression pattern was more apparent in rbWap65-1 than rbWap65-2 isoform. During
      thermal elevation, clear upregulation was found only for the rbWap65-1. In
      contrast, immune stimulations (bacterial challenges, viral infection and iron
      overload) activated more preferentially the rbWap65-2 isoform in overall,
      although the inducibility was affected by the kinds of stimulators and tissue
      types. Taken together, our data suggest that the two paralogue rbWap65 isoforms
      have experienced subfunctionalization and/or neofunctionalization during their
      evolutionary history, in which the rbWap65-2 has retained closer, functional
      orthology to the human HPX while the rbWap65-1 have been diversified to be more
      related with thermal acclimation physiology. 

PMID- 24434645
TI  - Identification of two secreted ferritin subunits involved in immune defense of
      Yesso scallop Patinopecten yessoensis.
AB  - As an important iron storage protein, ferritin plays a crucial role in the iron
      withholding defense system. In this study, two secreted ferritin subunits
      (PyFerS1 and PyFerS2) were identified from the Yesso scallop, Patinopecten
      yessoensis. The complete DNA sequences of the two ferritins are 7101 and 5359 bp,
      consisting of seven and five exons, respectively. The full-length cDNAs of
      PyFerS1 and PyFerS2 are 960 and 956 bp in length, encoding 228 and 220 amino
      acids, respectively. They have typical ferritin structures, with four long alpha
      helices, one short alpha-helix and an L-loop. Signal peptides were found at the N
      terminus of both ferritins, and phylogenetic analysis showed that they both
      clustered with secreted mollusc ferritins. PyFerS1 possesses all seven conserved
      residues of the ferroxidase center, whereas PyFerS2 only has two. Real-time PCR
      analysis indicated high expression level of PyFerS2 in the D-shaped larvae, and
      PyFerS1 in both D-shaped larvae and fertilized eggs. In adult scallops, PyFerS1
      was only detected in the hepatopancreas, whereas PyFerS2 was detected in both
      hepatopancreas and mantle. After the scallops were challenged by iron ion or
      bacteria Vibrio anguillarum, the expression of both PyFerS1 and PyFerS2 was
      significantly elevated, suggesting they may play a role in scallop innate immune
      defense. For the first time, secreted ferritins were cloned and comprehensively
      characterized in bivalve molluscs. It will assist in better understanding of the
      role of secreted ferritins in bivalve innate immunity. 

PMID- 24434647
TI  - Proteomic identification, characterization and expression analysis of
      Ctenopharyngodon idella VDAC1 upregulated by grass carp reovirus infection.
AB  - Voltage-dependent anion channels (VDACs) located in the mitochondrial outer
      membrane are mitochondrial porins that play central roles in regulating cell life
      and death. In this present report, the VDAC protein 1 from grass carp
      Ctenopharyngodon idella (designated as CiVDAC1) was found to be upregulated by
      grass carp reovirus (GCRV) infection through two-dimensional gel electrophoresis
      and protein analysis of infected C. idella kidney (CIK) cells. The full-length
      cDNA of CiVDAC1 was 995 bp with an open reading frame (ORF) of 852 bp that
      encodes a putative 283-amino acid protein. Phylogenic analysis revealed that the
      complete ORF of CiVDAC1 demonstrated high identity with well characterized
      mammalian homologs. The deduced CiVDAC1 protein contains an alpha-helix at the
      amino terminal, 19 membrane-spanning beta-strands, and one eukaryotic
      mitochondrial porin signature motif. Tissue tropism analysis indicated that
      CiVDAC1 is abundant in muscle, heart, skin, swim bladder, trunk kidney and
      spleen. Transcriptional expression profiles indicated that the CiVDAC1 gene was
      upregulated upon viral challenge in a manner similar to the Mx2 gene, which is a
      marker gene used to indicate activation of innate antiviral immunity. Similar
      expression patterns of the CiVDAC1 gene were observed in CIK cells stimulated
      with poly (I:C), as well as grass carp kidney tissue challenged with GCRV in
      vivo. CiVDAC1 silencing in CIK cells had no impact on progeny virus production,
      but over-expression of CiVDAC1 in vivo showed strongly protect against challenge
      with live virus. To interpret the role of other VDAC proteins in viral
      pathogenesis, CiVDAC2 was characterized and showed to respond positively to GCRV
      challenge, which suggested that CiVDAC2 might functionally complement CiVDAC1 in
      C. idella. The present data did demonstrate that CiVDAC1 might be mediated grass
      carp antiviral immune response. 

PMID- 24434648
TI  - Knockdown of a novel G-protein pathway suppressor 2 (GPS2) leads to shrimp
      mortality by exuvial entrapment during ecdysis.
AB  - A novel G-protein pathway suppressor 2 (GPS2) has been identified from hemocytes
      of the whiteleg shrimp Penaeus vannamei (Pv) and appears to play a role in
      ecdysis. The full-length of PvGPS2 cDNA consisted of a 1230-bp open reading
      frame, encoding 409 deduced amino acids with significant sequence homology to
      GPS2 sequences of crustaceans and insects. RT-PCR revealed that PvGPS2 was
      expressed in all P. vannamei tissues examined, but that expression was molt stage
      specific in eyestalk tissue. Relative expression was higher in the period before
      molting (i.e., intermolt and pre-molt stages) than in the post-molt stage. When
      double-stranded RNA (dsRNA)-mediated RNA interference was employed to inhibit
      PvGPS2 formation in shrimp, it led to significant mortality due to unsuccessful
      separation of new cuticle from old cuticle (exuvial entrapment) during ecdysis. 

PMID- 24434649
TI  - Dose calibration optimization and error propagation in polymer gel dosimetry.
AB  - This study reports on the relative precision, relative error, and dose
      differences observed when using a new full-image calibration technique in NIPAM
      based x-ray CT polymer gel dosimetry. The effects of calibration parameters (e.g.
      gradient thresholding, dose bin size, calibration fit function, and spatial
      remeshing) on subsequent errors in calibrated gel images are reported. It is
      found that gradient thresholding, dose bin size, and fit function all play a
      primary role in affecting errors in calibrated images. Spatial remeshing induces
      minimal reductions or increases in errors in calibrated images. This study also
      reports on a full error propagation throughout the CT gel image pre-processing
      and calibration procedure thus giving, for the first time, a realistic view of
      the errors incurred in calibrated CT polymer gel dosimetry. While the work is
      based on CT polymer gel dosimetry, the formalism is valid for and easily extended
      to MRI or optical CT dosimetry protocols. Hence, the procedures developed within
      the work are generally applicable to calibration of polymer gel dosimeters. 

PMID- 24434650
TI  - Nutritional therapy, phosphate control and renal protection.
AB  - Dietary management of chronic kidney disease (CKD) focusses on limiting the
      intake of substances that might accumulate to toxic levels (such as potassium,
      phosphorus or salt) and, although still a matter of debate for some, restricting
      dietary protein to retard kidney damage. Recent evidence brings the opportunity
      to revisit the role of a healthy diet on disease progression and on some of the
      cardiometabolic complications of moderate/advanced CKD, such as inflammation or
      oxidative stress control. This review provides a brief overview of dietary
      strategies that delay CKD progression and CKD complications, and discusses
      currently limited data addressing the development of malnutrition and protein
      energy wasting before dialysis initiation.

PMID- 24434651
TI  - Multiple breath washout is feasible in the clinical setting and detects abnormal
      lung function in infants and young children with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) lung disease starts in the first months of life
      often before the onset of clinical symptoms. Multiple breath washout (MBW)
      detects abnormal lung function in infants and young children in the laboratory
      setting. OBJECTIVE: The aim of this study was to determine the feasibility of MBW
      in 0- to 4-year-old children with CF and non-CF controls in the clinical setting.
      METHODS: Fourteen children with CF (mean age 1.3 +/- 1.0 years) and 26 age
      matched non-CF controls were sedated with chloral hydrate and MBW was performed
      with sulfur hexafluoride. RESULTS: MBW measurements were successful in 27 of 40
      children (67.5%). The mean lung clearance index (LCI) was significantly higher in
      CF patients compared to non-CF controls (p = 0.006). Further, the frequency of
      elevated LCI (z-score >1.96) was significantly increased in CF patients compared
      to controls (p = 0.0003). CONCLUSIONS: We conclude that MBW is feasible and
      sensitive to detect abnormal lung function in infants and young children with CF
      in the clinical setting.

PMID- 24434652
TI  - NR5A1 gene mutations: clinical, endocrine and genetic features in two girls with
      46,XY disorder of sex development.
AB  - BACKGROUND: Steroidogenic factor 1, encoded by the NR5A1 gene, is a key regulator
      of endocrine function within the hypothalamic-pituitary-steroidogenic axis. Both
      homozygous, compound heterozygous and heterozygous mutations in the NR5A1 gene
      may determine 46,XY disorders of sex development (DSD). PATIENTS AND METHODS:
      NR5A1 gene sequencing was performed in a cohort of 6 patients with 46,XY DSD
      without specific diagnosis. RESULTS: Heterozygous NR5A1 gene mutations were found
      in 2 girls, aged 0.5 years and 14 years. The older girl harbored the c.250C>T
      transition in exon 4 (p.Arg84Cys), previously reported in a Japanese girl. The
      younger girl presented a de novo novel exon 6 heterozygous frameshift mutation
      (c.1074dupG) in codon 359 associated with the p.Gly146Ala polymorphism the latter
      inherited from her father. This baby showed severe impairment of androgen
      secretion from the first months of life. Overt adrenal insufficiency did not
      occur, but the older girl showed subnormal cortisol peak after ACTH stimulation.
      CONCLUSIONS: NR5A1 gene mutations are a relatively frequent cause of 46,XY DSD in
      humans. Clear indications for management of these individuals remain elusive,
      mainly when diagnosis is made in infancy. Long-term monitoring of adrenal
      function should be recommended.

PMID- 24434653
TI  - RRM1 maintains centrosomal integrity via CHK1 and CDK1 signaling during
      replication stress.
AB  - DNA lesion-induced centrosomal abnormalities during the replication phase are
      relatively unknown. Here, we report that RNAi-mediated depletion of RRM1 induces
      cell-cycle arrest at the replication phase, along with severe DNA damage and
      centrosomal amplification. Interestingly, CHK1 depletion synergistically
      increased RRM1-depletion-induced centrosomal amplification. In response to
      hydroxyurea, CHK1 was delocalized from the centrosome by RRM1 depletion.
      Moreover, CDK1, which functions in centrosome separation and is inhibited by
      CHK1, was found to be essential for RRMI1-depletion-induced centrosomal
      amplification. Thus, we herein demonstrate that RRM1 preserves chromosomal
      stability via the CHK1- and CDK1-dependent stabilization of the centrosomal
      integrity at the replication stage. 

PMID- 24434655
TI  - Reliability reallocation models as a support tools in traffic safety analysis.
AB  - One of the essential questions placed before a road authority is where to act
      first, i.e. which road sections should be treated in order to achieve the desired
      level of reliability of a particular road, while this is at the same time the
      subject of this research. The paper shows how the reliability reallocation theory
      can be applied in safety analysis of a road consisting of sections. The model has
      been successfully tested using two apportionment techniques - ARINC and the
      minimum effort algorithm. The given methods were applied in the traffic safety
      analysis as a basic step, for the purpose of achieving a higher level of
      reliability. The previous methods used for selecting hazardous locations do not
      provide precise values for the required frequency of accidents, i.e. the time
      period between the occurrences of two accidents. In other words, they do not
      allow for the establishment of a connection between a precise demand for
      increased reliability (expressed as a percentage) and the selection of particular
      road sections for further analysis. The paper shows that reallocation models can
      also be applied in road safety analysis, or more precisely, as part of the
      measures for increasing their level of safety. A tool has been developed for
      selecting road sections for treatment on the basis of a precisely defined
      increase in the level of reliability of a particular road, i.e. the mean time
      between the occurrences of two accidents. 

PMID- 24434654
TI  - Carcinogenic metalloid arsenic induces expression of mdig oncogene through JNK
      and STAT3 activation.
AB  - Environmental or occupational exposure to arsenic, a chemical element classified
      as metalloid, has been associated with cancer of the lung, skin, bladder, liver,
      etc. Mdig (mineral dust-induced gene) is a newly identified oncogene linked to
      occupational lung diseases and lung cancer. It is unclear whether mdig is also
      involved in arsenic-induced malignant transformation of the lung cells. By using
      human bronchial epithelial cells and human lung cancer cell lines, we showed that
      arsenic was able to induce expression of mdig. We further demonstrated that this
      mdig induction by arsenic was partially dependent on the JNK and STAT3 signaling
      pathways. Disruption of the JNK or STAT3 by either chemical inhibitors or siRNAs
      diminished arsenic-induced accumulation of mdig mRNA and protein. Furthermore, we
      also showed that microRNA-21 (miR-21) and Akt were down-stream effectors of the
      JNK and STAT3 signaling pathways in arsenic-induced mdig expression. Transfection
      of the cells with anti-miR-21 or pre-treatment of the cells with Akt inhibitor
      blunted mdig induction by arsenic. Clinically, the levels of mdig can be applied
      to predict the disease progression, the first progression (FP), in non-small cell
      lung cancer (NSCLC) patients. Taken together, our data suggest that mdig may play
      important roles on the pathogenesis of arsenic-induced lung cancer and that JNK
      and STAT3 signaling pathways are essential in mediating arsenic-induced mdig
      expression. 

PMID- 24434657
TI  - Stakeholder consultation insights on the future of genomics at the clinical
      public health interface.
AB  - In summer 2011, the Centers for Disease Control and Prevention Office of Public
      Health Genomics conducted a stakeholder consultation, administered by the
      University of Michigan Center for Public Health and Community Genomics, and
      Genetic Alliance, to recommend priorities for public health genomics from 2012
      through 2017. Sixty-two responses from health professionals, administrators, and
      members of the public were pooled with 2 sets of key informant interviews and 3
      discussion groups. NVivo 9 and manual methods were used to organize themes. This
      review offers an interim analysis of progress with respect to the final
      recommendations, which demonstrated a strong interest in moving genomic
      discoveries toward implementation and comparative effectiveness (T3/T4)
      translational research. A translational research continuum exists with familial
      breast and ovarian cancer at one end and prostate cancer at the other. Cascade
      screening for inherited arrhythmia syndromes and hypercholesterolemia lags
      stakeholder recommendations in the United States but not in Europe;
      implementation of health service-based screening for Lynch syndrome, and
      integration into electronic health information systems, is on pace with the
      recommended timeline. A number of options exist to address deficits in the
      funding of translational research, particularly for oncogenomic gene expression
      profiling. The goal of personalized risk assessment necessitates both research
      progress (eg, in whole genome sequencing, as well as provider education in the
      differentiation of low- vs high-risk status. The public health approach supports
      an emphasis on genetic test validation while endorsing clinical translation
      research inclusion of an environmental and population-based perspective. 

PMID- 24434656
TI  - Association between MUC5B and TERT polymorphisms and different interstitial lung
      disease phenotypes.
AB  - TERT and MUC5B polymorphisms have been associated consistently with idiopathic
      pulmonary fibrosis (IPF) in recent genomewide genetic studies. However, it
      remains unclear how both loci contribute to the susceptibility to different
      entities of sporadic interstitial lung disease (ILD). We sought to test the
      associations of the 2 polymorphisms with IPF and non-IPF ILD entities in a white
      population. Associations between 2 polymorphisms in TERT (rs2736100) and MUC5B
      (rs35705950) and IPF or non-IPF sporadic ILD were tested using 227 patients with
      ILD and 689 control subjects. Genotypic data were also correlated with pulmonary
      functions measured in patients with ILD. As a result, rs2736100 and rs35705950
      were associated significantly and independently with ILD as a single phenotype
      (Odds ratio [OR], 1.29; 95% confidence interval [CI], 1.04-1.60; P = 2 * 10(-2);
      and OR, 2.22; 95% CI, 1.69-2.92; P = 7 * 10(-9); respectively). When considering
      IPF and "other ILD" (non-IPF) separately, rs35705950 had a stronger association
      with IPF (OR, 3.2; 95% CI, 2.21-4.63; P = 1.2 * 10(-10)) than with other ILD (OR,
      1.72; 95% CI, 1.22-2.42; P = 1.2 * 10(-3)). In contrast, rs2736100 was associated
      with other ILD (OR, 1.43; 95% CI, 1.11-1.85; P = 6.2 * 10(-3)) but not with IPF
      (OR, 1.08; 95% CI, 0.78-1.49; P > 0.05). Rs35705950 correlated significantly with
      increased pulmonary function (P < 0.05). It was also associated with ILD without
      airflow obstruction in both the IPF and other ILD groups (P < 0.01 for both), and
      conferred the highest risk for IPF without airflow obstruction (OR, 4.46; 95% CI,
      2.60-7.66; P = 4.5 * 10(-9)). Our study suggests that although both loci confer
      independent risks for ILD, rs35705950 may, in particular, contribute
      differentially to IPF and other ILD entities. Our study further highlights the
      genetic and phenotypic heterogeneity of ILD. 

PMID- 24434658
TI  - Towards terrain interaction prediction for bioinspired planetary exploration
      rovers.
AB  - Deployment of a small legged vehicle to extend the reach of future planetary
      exploration missions is an attractive possibility but little is known about the
      behaviour of a walking rover on deformable planetary terrain. This paper applies
      ideas from the developing study of granular materials together with a detailed
      characterization of the sinkage process to propose and validate a combined model
      of terrain interaction based on an understanding of the physics and micro
      mechanics at the granular level. Whilst the model reflects the complexity of
      interactions expected from a walking rover, common themes emerge which enable the
      model to be streamlined to the extent that a simple mathematical representation
      is possible without resorting to numerical methods. Bespoke testing and analysis
      tools are described which reveal some unexpected conclusions and point the way
      towards intelligent control and foot geometry techniques to improve thrust
      generation. 

PMID- 24434660
TI  - YouTube as a source of information about retinitis pigmentosa.

PMID- 24434659
TI  - Bimatoprost 0.01% vs bimatoprost 0.03%: a 12-month prospective trial of clinical
      and in vivo confocal microscopy in glaucoma patients.
AB  - PURPOSE: To evaluate the safety of two commercially available formulations of
      bimatoprost eye drops: 0.03 and 0.01% ophthalmic solutions. METHODS: This was a
      randomized, prospective, parallel-group, open-label, cohort study. A total of 60
      glaucoma patients (60 eyes) under bimatoprost 0.03% monotherapy since at least 1
      year were enrolled. Selected patients were randomized to receive a single drop of
      bimatoprost 0.01% (n=30) or bimatoprost 0.03% (n=30) ophthalmic solutions for 12
      months. Statistical analysis was performed using paired t-test and repeated
      measures ANOVA test. RESULTS: Global clinical score (the sum of pruritus,
      stinging/burning, blurred vision, sticky eye sensation, eye dryness sensation,
      and foreign body sensation) significantly decreased in the bimatoprost 0.01%
      group from baseline 4.7 +/- 3.8 to 2.9 +/- 2.3 (P < 0.001) and 2.5 +/- 2.0 (P <
      0.001) at 6-month and 12-month follow-ups, respectively. Comparison between
      groups showed differences at both follow-up visits (P = 0.003 and P < 0.001,
      respectively). In vivo confocal microscopy revealed a significant increase in
      goblet cell density in the bimatoprost 0.01% group compared with the bimatoprost
      0.03% group (P<0.001 at both follow-up visits). All functional parameters and
      conjunctival hyperemia improved in the bimatoprost 0.01% group at each follow-up
      visit (P < 0.05) and in comparison with bimatoprost 0.03% (P < 0.05). CONCLUSION:
      The results of this trial suggest that bimatoprost 0.01% eye drops seem to
      decrease the ocular discomfort with respect to bimatoprost 0.03% eye drops.

PMID- 24434661
TI  - Comparison of spectral domain and swept-source optical coherence tomography in
      pathological myopia.
AB  - PURPOSE: To compare optical coherence tomography (OCT) images obtained with swept
      source OCT (SS-OCT) and spectral domain OCT (SD-OCT) in pathological myopia.
      METHODS: This is a comparative observational cases series. Five patients with
      pathological myopia underwent SD-OCT and SS-OCT imaging. SS-OCT was performed
      using a prototype system (Topcon Medical Systems). SD-OCT was performed using
      enhanced depth imaging on the Heidelberg Spectralis OCT. The closest
      corresponding scans from the central subfield were compared. RESULTS: Eight eyes
      of five patients with pathological myopia were included (mean spherical
      equivalent: -16.00 +/- 4.70 D). Overall, SS-OCT better visualized retino
      choroidal structures. The choroid, inner segment (IS)/outer segment (OS) line,
      and external limiting membrane (ELM) were clearly seen in a higher proportion of
      SS-OCT than SD-OCT scans, (P<0.01 for all) whereas visualization of the sclera
      and retinal pigment epithelium (RPE) were similar. SS-OCT demonstrated
      foveoschisis in four eyes, with one of these not visible on SD-OCT. The wider SS
      OCT scan revealed additional pathology not visible using SD-OCT along the
      staphyloma walls in 4/8 images. These included incomplete posterior vitreous
      detachment in one eye and peripheral retinoschisis in 3/8 eyes. Vitreoschisis was
      visible in 3/8 SS-OCT images but not in the SD-OCT images. CONCLUSION: SS-OCT is
      useful for imaging the posterior staphyloma of pathological myopia, providing
      greater detail than SD-OCT.

PMID- 24434662
TI  - Cellular changes in tears associated with keratoconjunctival responses induced by
      nasal allergy.
AB  - BACKGROUND: Allergic keratoconjunctivitis occurs in a primary form, caused by an
      allergic reaction localized in the conjunctiva, and in a secondary form, induced
      by an allergic reaction originating in the nasal mucosa. Various hypersensitivity
      mechanisms involved in the keratoconjunctivitis forms result in different
      keratoconjunctival response types. PURPOSE: To investigate the cytologic changes
      in tears during the secondary immediate (SIKCR), late (SLKCR), and delayed
      (SDYKCR) keratoconjunctival responses. METHODS: In 61 patients, comprising 20
      SIKCRs, 23 SLKCRs, and 18 SDYKCRs, nasal provocation tests (NPTs) with allergens
      and 61 phosphate-buffered control challenges were repeated and supplemented with
      cell counting in the tears. RESULTS: The SIKCR (P<0.01), appearing 10-120 min
      after the NPT, was associated with increased eosinophil and mast cell counts in
      tears. The SLKCR (P<0.01), appearing 5-12 h after the NPT, was accompanied by
      increased counts of eosinophils, neutrophils, basophils, and conjunctival
      epithelial and goblet cells. The SDYKCR (P<0.05), appearing 24-48 h after NPT,
      was associated with increased counts of lymphocytes, neutrophils, monocytes,
      basophils, conjunctival epithelial, corneal epithelial and goblet cells.
      CONCLUSIONS: The SIKCR, SLKCR, and SDYKCR, induced by nasal allergy, were
      associated with different cellular profiles in the tears. The cells, except mast,
      epithelial and goblet cells, displaying no intracellular changes, migrated
      probably from the conjunctival capillaries, in response to the factors released
      during the primary allergic reaction in the nasal mucosa and subsequently
      penetrating into the conjunctiva. These results demonstrate a causal role of
      nasal allergy and diagnostic value of NPT combined with recording of ocular
      features and cellular profiles in tears in some keratoconjunctivitis patients.

PMID- 24434663
TI  - 'Toy' laser macular burns in children.
AB  - PURPOSE: Laser 'toys' can be purchased online and imported with relative ease;
      the variety of such devices is a potential public safety concern. We describe
      five children with maculopathy following exposure to laser 'toys'. METHODS: Case
      series of maculopathy following exposure to laser 'toys'. RESULTS: Five children
      were seen in our Ophthalmic Unit with macular injuries following exposure to
      laser 'toys'. Clinically, three children had an acute vitelliform-like
      maculopathy which resolved to leave sub-foveal retinal pigment epithelium changes
      with reduced vision. One case was complicated by a choroidal neovascular
      membrane. CONCLUSION: Laser 'toys', which resemble laser pointers, are
      increasingly available over the internet. Such 'toys' may not meet safety
      standards. Retinal injury in childhood following exposure to laser 'toys' is a
      public safety concern.

PMID- 24434664
TI  - Intravitreal bevacizumab injection in unrecognised early pregnancy.
AB  - PURPOSE: The use of intravitreal vascular endothelial growth factor (VEGF)
      inhibitor medications has widened considerably to include indications affecting
      females of reproductive age. PATIENTS AND METHODS: We present our experiences
      following intravitreal injection of bevacizumab during the first trimester of
      unrecognised pregnancies in four women. RESULTS: All our patients were
      inadvertently exposed to bevacizumab within the first trimester when placental
      growth and fetal organogenesis take place. There were three cases of pregnancy
      without complication and one case of complicated pregnancy in which there was a
      significant past obstetric history. CONCLUSION: This case series provides further
      insights into intravitreal injection of bevacizumab in early pregnancy. There is
      insufficient information to suggest that such use is safe, nor is there
      definitive evidence to suggest that it causes harm. We advise that
      ophthalmologists discuss pregnancy with women of childbearing age undergoing
      intraocular anti-VEGF injections. Should a woman become pregnant, counselling is
      needed to explain the potential risks and benefits, and the limited available
      data relating to the use of these agents in early pregnancy.

PMID- 24434665
TI  - Nodular regenerative hyperplasia causing portal hypertension in a patient with
      chronic graft versus host disease: response to sirolimus.

PMID- 24434666
TI  - Chronic obstructive pulmonary disease: getting it right. Does optimal management
      of chronic obstructive pulmonary disease alter disease progression and improve
      survival?
AB  - PURPOSE OF REVIEW: We live in a world where people live longer lives. The
      standardized mortality rate for many diseases is decreasing. Chronic obstructive
      pulmonary disease (COPD) is not following this trend. Over the last 10 years,
      interventions for COPD have been developed, but have any changed the prognosis or
      trajectory of this modern epidemic? We review the most recent and classical
      literature in order to answer this question. RECENT FINDINGS: Recent analyses of
      data have clarified which interventions are effective in COPD and which are not.
      New studies have defined what is achievable with the current therapies. Only two
      interventions have been demonstrated to improve survival: smoking cessation and
      long-term oxygen therapy. Other treatments do reduce exacerbations, improve lung
      function and improve the patient's quality of life, but do not affect
      physiological disease progression or mortality. SUMMARY: There is much work to
      do, not only to improve the treatments we have for this disease, but also to
      diagnose it early, intervene at the right time, reduce the treatment side-effects
      and most importantly understand the pathophysiology better. Moreover, we are duty
      bound to look at each patient and review what we are trying to achieve for each
      one through appropriate phenotyping as well as sometimes taking a more palliative
      approach.

PMID- 24434667
TI  - Imaging in occupational and environmental lung disease.
AB  - PURPOSE OF REVIEW: Work-related and environmental lung disease is increasing over
      time and new antigens causing pulmonary response are described in medical
      literature every year with more or less specific imaging findings. The purposes
      of this review are to highlight the current role of imaging, describe classic as
      well as uncommon high-resolution computed tomography (HRCT) patterns helpful in
      guiding diagnosis and update the recent literature on this topic. RECENT
      FINDINGS: Recent literature on imaging of occupational and environmental lung
      disease is scarce and is predominantly based on the HRCT appearance related to
      specific antigen exposure and on prognostic significance of findings. SUMMARY:
      Knowledge of imaging modality potential and radiologic appearance may guide
      identification, characterization and follow-up of old and new occupational and
      environmental lung diseases. HRCT plays a key role in this context, having
      radiation exposure as a major limitation, especially in asymptomatic patients.
      Low-dose HRCT has the potential to be employed for screening and surveillance of
      the exposed individuals. However, future research is needed to further this
      field.

PMID- 24434668
TI  - Synthesis and broad-spectrum antiviral activity of some novel benzo-heterocyclic
      amine compounds.
AB  - A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives
      were synthesized and assayed to determine their in vitro broad-spectrum antiviral
      activities. The biological results showed that most of our synthesized compounds
      exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f
      (IC50=3.21-5.06 MUM) and 3g (IC50=0.71-34.87 MUM) showed potent activity towards
      both RNA viruses (influenza A, HCV and Cox B3 virus) and a DNA virus (HBV) at low
      micromolar concentrations. An SAR study showed that electron-withdrawing
      substituents located on the aromatic or heteroaromatic ring favored antiviral
      activity towards RNA viruses.

PMID- 24434669
TI  - Pd-catalyzed amination in the synthesis of a new family of macropolycyclic
      compounds comprising diazacrown ether moieties.
AB  - N,N'-bis(bromobenzyl) and N,N'-bis(halopyridinyl) derivatives of diaza-12-crown
      4, diaza-15-crown-5 and diaza-18-crown-6 ethers were synthesized in high yields.
      The Pd-catalyzed macrocyclization reactions of these compounds were carried out
      using a variety of polyamines and oxadiamines were carried out to give novel
      macrobicyclic and macrotricyclic compounds of the cryptand type. The dependence
      of the yields of macropolycycles on the nature of the starting diazacrown
      derivatives and polyamines was established. Generally N,N'-bis(3-bromobenzyl)
      substituted diazacrown ethers and oxadiamines provided better yields of the
      target products. The highest yield of the macrobicyclic products reached 57%. 

PMID- 24434670
TI  - Influence of disulfide connectivity on structure and bioactivity of alpha
      conotoxin TxIA.
AB  - Cone snails express a sophisticated arsenal of small bioactive peptides known as
      conopeptides or conotoxins (CTxs). Through evolutionary selection, these peptides
      have gained the ability to interact with a range of ion channels and receptors,
      such as nicotinic acetylcholine receptors (nAChRs). Here, we used reversed-phase
      high performance liquid chromatography (RP-HPLC) and electrospray ionization-mass
      spectrometry (ESI-MS) to explore the venom peptide diversity of Conus textile, a
      species of cone snail native to Hainan, China. One fraction of C. textile crude
      venom potently blocked alpha3beta2 nAChRs. Subsequent purification, synthesis,
      and tandem mass spectrometric analysis demonstrated that the most active compound
      in this fraction was identical to alpha-CTx TxIA, an antagonist of alpha3beta2
      nAChRs. Then three disulfide isoforms of alpha-CTx TxIA were synthesized and
      their activities were investigated systematically for the first time. As we
      observed, disulfide isomerisation was particularly important for alpha-CTx TxIA
      potency. Although both globular and ribbon isomers showed similar retention times
      in RP-HPLC, globular TxIA potently inhibited alpha3beta2 nAChRs with an IC50 of
      5.4 nM, while ribbon TxIA had an IC50 of 430 nM. In contrast, beads isomer had
      little activity towards alpha3beta2 nAChRs. Two-step oxidation synthesis produced
      the highest yield of alpha-CTx TxIA native globular isomer, while a one-step
      production process based on random oxidation folding was not suitable. In
      summary, this study demonstrated the relationship between conotoxin activity and
      disulfide connectivity on alpha-CTx TxIA. 

PMID- 24434671
TI  - EPR spectroscopy of a clinically active (1:2) copper(II)-histidine complex used
      in the treatment of Menkes disease: a Fourier transform analysis of a fluid CW
      EPR spectrum.
AB  - Redox active transition metal ions (e.g., iron and copper) have been implicated
      in the etiology of many oxidative stress-related diseases including also
      neurodegenerative disorders. Unbound copper can catalyze formation of reactive
      oxygen species (hydroxyl radicals) via Fenton reaction/Haber-Weiss chemistry and
      therefore, under physiological conditions, free copper is potentially toxic and
      very rarely exists inside cells. Copper(II) bound to the aminoacid L-histidine
      represents a species discovered in blood in the mid 60s and since then extensive
      research on this complex was carried out. Copper bound to L-histidine represents
      an exchangeable pool of copper(II) in equilibrium with the most abundant blood
      plasma protein, human serum albumin. The structure of this complex, in aqueous
      solution, has been a subject of many studies and reviews, however without
      convincing success. The significance of the (1:2) copper(II)-L-histidine complex
      at physiological pH documents its therapeutic applications in the treatment of
      Menkes disease and more recently in the treatment of infantile hypertrophic
      cardioencephalomyopathy. While recently the (1:2) Cu(II)-L-His complex has been
      successfully crystallized and the crystal structure was solved by X-ray
      diffraction, the structure of the complex in fluid solution at physiological pH
      is not satisfactorily known. The aim of this paper is to study the (1:2) Cu(II)-L
      histidine complex at low temperatures by X-band and S-band EPR spectroscopy and
      at physiological pH at room temperature by Fourier transform CW-EPR spectroscopy.

PMID- 24434672
TI  - Fatty acid profile of cheese from dairy goats fed a diet enriched with castor,
      sesame and faveleira vegetable oils.
AB  - The addition of vegetable oils to the diets of dairy goats is an alternative to
      supplemental feeding during the dry period and improves the lipid profile of milk
      and by-products. Cheeses were produced using milk from cross bred goats
      (Saanen*Alpina) fed diets enriched with 4% vegetable oil (faveleira, sesame or
      castor), the fatty acid profile of cheeses was studied. Supplementation with
      vegetable oils did not increase the total fat percentage of the cheese (p>=0.05)
      but did increase the percentage of CLA isomers, long-chain fatty acids (LCFA) and
      polyunsaturated fatty acids (PUFA); in addition, the index of desirable fatty
      acids (DFA--expressed as the sum of unsaturated fatty acids plus stearic acid)
      was increased for cheese made from milk from goats fed sesame or faveleira oil.
      Cheeses may have had increased percentages of cis-9,trans-11-CLA due to the
      supplementation of animal diets with vegetable oils rich in C18:2, such as
      faveleira and sesame oils. The fatty acid profile of goat cheese did not change
      significantly in response to the use of castor oil. Thus, the addition of sesame
      and faveleira oils to goat diets positively altered the fatty acid profile, which
      improved the nutritional characteristics of the fat present in goat cheese.

PMID- 24434673
TI  - Coupling bioorthogonal chemistries with artificial metabolism: intracellular
      biosynthesis of azidohomoalanine and its incorporation into recombinant proteins.
AB  - In this paper, we present a novel, "single experiment" methodology based on
      genetic engineering of metabolic pathways for direct intracellular production of
      non-canonical amino acids from simple precursors, coupled with expanded genetic
      code. In particular, we engineered the intracellular biosynthesis of L
      azidohomoalanine from O-acetyl-L-homoserine and NaN3, and achieved its direct
      incorporation into recombinant target proteins by AUG codon reassignment in a
      methionine-auxotroph E. coli strain. In our system, the host's methionine
      biosynthetic pathway was first diverted towards the production of the desired non
      canonical amino acid by exploiting the broad reaction specificity of recombinant
      pyridoxal phosphate-dependent O-acetylhomoserine sulfhydrylase from
      Corynebacterium glutamicum. Then, the expression of the target protein barstar,
      accompanied with efficient L-azidohomoalanine incorporation in place of L
      methionine, was accomplished. This work stands as proof-of-principle and paves
      the way for additional work towards intracellular production and site-specific
      incorporation of biotechnologically relevant non-canonical amino acids directly
      from common fermentable sources. 

PMID- 24434674
TI  - Preparation of 2'-13C-L-histidine starting from 13C-thiocyanate: synthetic access
      to any site-directed stable isotope enriched L-histidine.
AB  - 1-Benzyl-2-(methylthio)-imidazole-5-ketone is obtained in a few simple steps
      starting from thiocyanate and glycine amide (glycin). Subsequent treatment with
      diethyl phosphorocyanidate and functional group manipulations gives 1-benzyl-5
      chloromethyl-imidazolium chloride. This compound is converted under mild
      O'Donnell conditions into the corresponding L-histidine derivative. After
      deprotection L-histidine is obtained in good yield and 99% enantiomeric excess.
      2'-13C-L-Histidine has been obtained via this new scheme with high (99%) 13C
      incorporation starting with commercially available 13C- thiocyanate. This
      synthetic scheme allows access to any isotopomer of L-histidine and many other
      biologically important imidazole derivatives. 

PMID- 24434675
TI  - Using sulcal and gyral measures of brain structure to investigate benefits of an
      active lifestyle.
AB  - BACKGROUND: Physical activity is associated with brain and cognitive health in
      ageing. Higher levels of physical activity are linked to larger cerebral volumes,
      lower rates of atrophy, better cognitive function and a lower risk of cognitive
      decline and dementia. Neuroimaging studies have traditionally focused on
      volumetric brain tissue measures to test associations between factors of interest
      (e.g. physical activity) and brain structure. However, cortical sulci may provide
      additional information to these more standard measures. METHOD: Associations
      between physical activity, brain structure, and cognition were investigated in a
      large, community-based sample of cognitively healthy individuals (N=317) using
      both sulcal and volumetric measures. RESULTS: Physical activity was associated
      with narrower width of the Left Superior Frontal Sulcus and the Right Central
      Sulcus, while volumetric measures showed no association with physical activity.
      In addition, Left Superior Frontal sulcal width was associated with processing
      speed and executive function. DISCUSSION: These findings suggest sulcal measures
      may be a sensitive index of physical activity related to cerebral health and
      cognitive function in healthy older individuals. Further research is required to
      confirm these findings and to examine how sulcal measures may be most effectively
      used in neuroimaging.

PMID- 24434676
TI  - Coherent slow cortical potentials reveal a superior localization of resting-state
      functional connectivity using voltage-sensitive dye imaging.
AB  - The resting-state functional connectivity (RSFC) of spontaneous hemodynamic
      fluctuations is widely used to investigate large-scale functional brain networks
      based on neurovascular mechanisms. However, high-resolution RSFC networks based
      on neural activity have not been disclosed to explore the neural basis of these
      spontaneous hemodynamic signals. The present study examines the neural RSFC
      networks in mice at high spatial resolution using optical imaging with voltage
      sensitive dyes (VSDs). Our results show that neural RSFC networks for the slow
      cortical potentials (0.1-4Hz) showed similar correlation patterns to the RSFC
      networks for the spontaneous hemodynamic signals, indicating a tight coupling
      between the slow cortical potential and the spontaneous hemodynamic signals
      during rest, but the bilateral symmetry of the RSFC networks for the slow
      cortical potentials was significantly lower than that for the spontaneous
      hemodynamic signals. Moreover, similar asymmetric neural activation patterns
      could also be found between the bilateral cortexes after stimulating the paws of
      mice. By increasing anesthetic levels to induce the reduction of consciousness,
      the RSFC networks for the slow cortical potentials persisted, but those for the
      spontaneous hemodynamic signals became discrete. These results suggest that the
      coherent slow cortical potentials underlie the spontaneous hemodynamic
      fluctuations and reveal a superior localization of RSFC networks. VSD imaging may
      potentially be used to examine the RSFC of neural activity, particularly under
      conditions of impaired neurovascular coupling. 

PMID- 24434677
TI  - A neural mechanism for recognizing speech spoken by different speakers.
AB  - Understanding speech from different speakers is a sophisticated process,
      particularly because the same acoustic parameters convey important information
      about both the speech message and the person speaking. How the human brain
      accomplishes speech recognition under such conditions is unknown. One view is
      that speaker information is discarded at early processing stages and not used for
      understanding the speech message. An alternative view is that speaker information
      is exploited to improve speech recognition. Consistent with the latter view,
      previous research identified functional interactions between the left- and the
      right-hemispheric superior temporal sulcus/gyrus, which process speech- and
      speaker-specific vocal tract parameters, respectively. Vocal tract parameters are
      one of the two major acoustic features that determine both speaker identity and
      speech message (phonemes). Here, using functional magnetic resonance imaging
      (fMRI), we show that a similar interaction exists for glottal fold parameters
      between the left and right Heschl's gyri. Glottal fold parameters are the other
      main acoustic feature that determines speaker identity and speech message
      (linguistic prosody). The findings suggest that interactions between left- and
      right-hemispheric areas are specific to the processing of different acoustic
      features of speech and speaker, and that they represent a general neural
      mechanism when understanding speech from different speakers. 

PMID- 24434678
TI  - Comparison of three-shell and simplified volume conductor models in
      magnetoencephalography.
AB  - Experimental MEG source imaging studies have typically been carried out with
      either a spherically symmetric head model or a single-shell boundary-element
      (BEM) model that is shaped according to the inner skull surface. The concepts and
      comparisons behind these simplified models have led to misunderstandings
      regarding the role of skull and scalp in MEG. In this work, we assess the forward
      model errors due to different skull/scalp approximations and due to differences
      and errors in model geometries. We built five anatomical models of a volunteer
      using a set of T1-weighted MR scans and three common toolboxes. Three of the
      models represented typical models in experimental MEG, one was manually
      constructed, and one contained a major segmentation error at the skull base. For
      these anatomical models, we built forward models using four simplified approaches
      and a three-shell BEM approach that has been used as reference in previous
      studies. Our reference model contained in addition the skull fine-structure
      (spongy bone). We computed signal topographies for cortically constrained sources
      in the left hemisphere and compared the topographies using relative error and
      correlation metrics. The results show that the spongy bone has a minimal effect
      on MEG topographies, and thus the skull approximation of the three-shell model is
      justified. The three-shell model performed best, followed by the corrected-sphere
      and single-shell models, whereas the local-spheres and single-sphere models were
      clearly worse. The three-shell model was the most robust against the introduced
      segmentation error. In contrast to earlier claims, there was no noteworthy
      difference in the computation times between the realistically-shaped and sphere
      based models, and the manual effort of building a three-shell model and a
      simplified model is comparable. We thus recommend the realistically-shaped three
      shell model for experimental MEG work. In cases where this is not possible, we
      recommend a realistically-shaped corrected-sphere or single-shell model. 

PMID- 24434680
TI  - Influence of different cosmetic formulations on the human skin barrier.
AB  - The human skin barrier is an important part of the skin's intactness and its
      functionality is a precondition for healthy skin. Ingredients in cosmetic
      formulations, especially penetration enhancers, can influence this barrier
      function as they transport active agents into deeper skin layers. In this study
      different cosmetic formulations were tested by 60 healthy female volunteers over
      a period of 4 weeks. The skin hydration and barrier function before and during
      the application were measured. Significant changes in both parameters were
      determined. A negative influence on the barrier function by penetration enhancers
      could be observed, but it was also found that lamellar lipid structures
      (DermaMembranSysteme(r), DMS(r)) are able to enhance the skin barrier. Both
      penetration enhancers as well as DMS can increase skin hydration.

PMID- 24434681
TI  - Dual source and dual detector arrays tetrahedron beam computed tomography for
      image guided radiotherapy.
AB  - Cone-beam computed tomography (CBCT) is an important online imaging modality for
      image guided radiotherapy. But suboptimal image quality and the lack of a real
      time stereoscopic imaging function limit its implementation in advanced treatment
      techniques, such as online adaptive and 4D radiotherapy. Tetrahedron beam
      computed tomography (TBCT) is a novel online imaging modality designed to improve
      on the image quality provided by CBCT. TBCT geometry is flexible, and multiple
      detector and source arrays can be used for different applications. In this paper,
      we describe a novel dual source-dual detector TBCT system that is specially
      designed for LINAC radiation treatment machines. The imaging system is positioned
      in-line with the MV beam and is composed of two linear array x-ray sources
      mounted aside the electrical portal imaging device and two linear arrays of x-ray
      detectors mounted below the machine head. The detector and x-ray source arrays
      are orthogonal to each other, and each pair of source and detector arrays forms a
      tetrahedral volume. Four planer images can be obtained from different view angles
      at each gantry position at a frame rate as high as 20 frames per second. The
      overlapped regions provide a stereoscopic field of view of approximately 10-15
      cm. With a half gantry rotation, a volumetric CT image can be reconstructed
      having a 45 cm field of view. Due to the scatter rejecting design of the TBCT
      geometry, the system can potentially produce high quality 2D and 3D images with
      less radiation exposure. The design of the dual source-dual detector system is
      described, and preliminary results of studies performed on numerical phantoms and
      simulated patient data are presented. 

PMID- 24434679
TI  - Oscillatory activity in neocortical networks during tactile discrimination near
      the limit of spatial acuity.
AB  - Oscillatory interactions within functionally specialized but distributed brain
      regions are believed to be central to perceptual and cognitive functions. Here,
      using human scalp electroencephalography (EEG) recordings combined with source
      reconstruction techniques, we study how oscillatory activity functionally
      organizes different neocortical regions during a tactile discrimination task near
      the limit of spatial acuity. While undergoing EEG recordings, blindfolded
      participants felt a linear three-dot array presented electromechanically, under
      computer control, and reported whether the central dot was offset to the left or
      right. The average brain response differed significantly for trials with correct
      and incorrect perceptual responses in the timeframe approximately between 130 and
      175ms. During trials with correct responses, source-level peak activity appeared
      in the left primary somatosensory cortex (SI) at around 45ms, in the right
      lateral occipital complex (LOC) at 130ms, in the right posterior intraparietal
      sulcus (pIPS) at 160ms, and finally in the left dorsolateral prefrontal cortex
      (dlPFC) at 175ms. Spectral interdependency analysis of activity in these nodes
      showed two distinct distributed networks, a dominantly feedforward network in the
      beta band (12-30Hz) that included all four nodes and a recurrent network in the
      gamma band (30-100Hz) that linked SI, pIPS and dlPFC. Measures of network
      activity in both bands were correlated with the accuracy of task performance.
      These findings suggest that beta and gamma band oscillatory networks coordinate
      activity between neocortical regions mediating sensory and cognitive processing
      to arrive at tactile perceptual decisions. 

PMID- 24434682
TI  - Determination of the self-association residues within a homomeric and a
      heteromeric AAA+ enhancer binding protein.
AB  - The sigma(54)-dependent transcription in bacteria requires specific activator
      proteins, bacterial enhancer binding protein (bEBP), members of the AAA+ (ATPases
      Associated with various cellular Activities) protein family. The bEBPs usually
      form oligomers in order to hydrolyze ATP and make open promoter complexes. The
      bEBP formed by HrpR and HrpS activates transcription from the sigma(54)-dependent
      hrpL promoter responsible for triggering the Type Three Secretion System in
      Pseudomonas syringae pathovars. Unlike other bEBPs that usually act as
      homohexamers, HrpR and HrpS operate as a highly co-dependent heterohexameric
      complex. To understand the organization of the HrpRS complex and the HrpR and
      HrpS strict co-dependence, we have analyzed the interface between subunits using
      the random and directed mutagenesis and available crystal structures of several
      closely related bEBPs. We identified key residues required for the self
      association of HrpR (D32, E202 and K235) with HrpS (D32, E200 and K233), showed
      that the HrpR D32 and HrpS K233 residues form interacting pairs directly involved
      in an HrpR-HrpS association and that the change in side-chain length at position
      233 in HrpS affects self-association and interaction with the HrpR and
      demonstrated that the HrpS D32, E200 and K233 are not involved in negative
      regulation imposed by HrpV. We established that the equivalent residues K30, E200
      and E234 in a homo-oligomeric bEBP, PspF, are required for the subunit
      communication and formation of an oligomeric lock that cooperates with the ATP
      gamma-phosphate sensing PspF residue R227, providing insights into their roles in
      the heteromeric HrpRS co-complex. 

PMID- 24434683
TI  - Transient versus persistent acute kidney injury and the diagnostic performance of
      fractional excretion of urea in critically ill patients.
AB  - AIMS: To evaluate the performance of fractional excretion of urea (FeU) for
      differentiating transient (T) from persistent (P) acute kidney injury (AKI) and
      to assess performance of FeU in predicting AKI in patients admitted to the ICU.
      METHODS: We performed secondary analysis of a multicenter prospective
      observational cohort study on the predictive performance of biological markers
      for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging.
      RESULTS: Of 150 patients, 51 and 41 patients were classified as having T-AKI and
      P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI
      from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49-0.73). The
      diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor
      as well (AUC-ROC = 0.61; 95% CI: 0.47-0.74, and 0.58; 95% CI: 0.43-0.73,
      respectively). CONCLUSIONS: FeU does not seem to be helpful in differentiating T-
      from P-AKI in critically ill patients and it is a poor predictor of AKI.

PMID- 24434684
TI  - Hemoadsorption of high-mobility group box chromosomal protein 1 using a column
      for large animals.
AB  - BACKGROUND: High-mobility group box chromosomal protein 1 (HMGB1) has recently
      been identified as an important mediator of various kinds of acute and chronic
      inflammation. A method for efficiently removing HMGB1 from the systemic
      circulation could be a promising therapy for HMGB1-mediated inflammatory
      diseases. MATERIALS AND METHODS: In this study, we produced a new adsorbent
      material by chemically treating polystyrene fiber. We first determined whether
      the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1
      solution and a plasma sample from a swine model of acute liver failure. We then
      constructed a column by embedding fabric sheets of the newly developed fibers
      into a cartridge and tested the ability of the column to reduce plasma HMGB1
      levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute
      liver failure. RESULTS: The in vitro adsorption test of the new fiber showed high
      performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and
      94% in the acute liver failure swine plasma, 2 h incubation at 37 degrees C; p <
      0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the
      HMGB1 concentration at the outlet versus the inlet of the column was
      significantly lower in swine hemoperfused with the newly developed column (53 and
      61% at the beginning and end of perfusion, respectively) than in those animals
      hemoperfused with the control column (94 and 93% at the beginning and end of
      perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of
      HMGB1 was significantly lower during perfusion with the new column than with the
      control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion).
      CONCLUSION: These data suggest that the newly developed column has the potential
      to effectively adsorb HMGB1 during hemoperfusion in swine.

PMID- 24434685
TI  - Therapeutic efficacy of topical calcineurin inhibitors in plasma cell balanitis:
      case series and review of the literature.
AB  - Plasma cell balanitis of Zoon (PCBZ) and plasma cell vulvitis (PCV) are
      characterized as idiopathic, benign, chronic irritant mucositis. The clinical
      symptoms and signs usually persist or reappear after treatment withdrawal.
      Therefore, many therapies have been tried and are available. Recently, several
      reports of PCBZ and PCV treated with calcineurin inhibitors, tacrolimus and
      pimecrolimus, have been reported in the literature. We present 9 cases of PCBZ
      treated with tacrolimus 0.1% ointment (Protopic, Toyama, Japan) that showed good
      therapeutic results within 4 weeks of treatment, and we review the literature of
      PCBZ and PCV and their response to these topical immunomodulators. Based on the
      current literature and on the anecdotal experience, we believe that topical
      calcineurin inhibitors may serve as a therapeutic option in recalcitrant plasma
      cell balanitis and vulvitis.

PMID- 24434686
TI  - Phytocompounds for the control of human enteric viruses.
AB  - Plant extracts and associated polyphenols are known for their varied health
      benefits that include antioxidant effects and antimicrobial properties. The
      increasing consumer demand for cost-effective and natural alternatives to
      chemically-synthesized antimicrobials and therapeutics that are also sustainable
      makes the field of phytochemical research rather intriguing and challenging.
      Human enteric viruses are increasingly recognized worldwide as significant causes
      of human disease in adults and children, alike. In the absence of available
      vaccines for the human noroviruses, plant extracts are gaining popularity for the
      prevention and treatment of viral diseases. Research on plant extracts
      (particularly polyphenols derived from fruits) for human enteric virus control
      will be briefly summarized in this article. 

PMID- 24434687
TI  - Diversity-oriented synthesis as a tool for identifying new modulators of mitosis.
AB  - The synthesis of diverse three-dimensional libraries has become of paramount
      importance for obtaining better leads for drug discovery. Such libraries are
      predicted to fare better than traditional compound collections in phenotypic
      screens and against difficult targets. Herein we report the diversity-oriented
      synthesis of a compound library using rhodium carbenoid chemistry to access
      structurally diverse three-dimensional molecules and show that they access
      biologically relevant areas of chemical space using cheminformatic analysis. High
      content screening of this library for antimitotic activity followed by chemical
      modification identified 'Dosabulin', which causes mitotic arrest and cancer cell
      death by apoptosis. Its mechanism of action is determined to be microtubule
      depolymerization, and the compound is shown to not significantly affect
      vinblastine binding to tubulin; however, experiments suggest binding to a site
      vicinal or allosteric to Colchicine. This work validates the combination of
      diversity-oriented synthesis and phenotypic screening as a strategy for the
      discovery of biologically relevant chemical entities. 

PMID- 24434688
TI  - Gray matter volume abnormalities in type 2 diabetes mellitus with and without
      mild cognitive impairment.
AB  - This study sought to evaluate the potential brain gray matter (GM) volume changes
      that occur with the transition from normal cognition to mild cognitive impairment
      (MCI) in patients with type 2 diabetes mellitus (T2DM) using voxel-based
      morphometry (VBM). VBM analyses of brain GM based on magnetic resonance imaging
      (MRI) data were performed on 28 T2DM patients with MCI, 25 T2DM patients without
      MCI, 28 MCI patients and 29 healthy controls (HC). Compared with the HC, the T2DM
      patients both with and without MCI showed significantly decreased total GM
      volume. Furthermore, the VBM results indicated that the T2DM patients without MCI
      exhibited extensively decreased GM volume compared with the HC in certain brain
      regions, including the superior and middle temporal gyrus (MTG), the superior and
      medial frontal gyrus and the middle occipital gyrus. In addition to more
      extensive GM atrophy in the aforementioned brain regions, the medial temporal
      lobe also exhibited GM loss in the T2DM patients with MCI. Furthermore, relative
      to the patients without MCI, only the left MTG exhibited a lower GM volume in the
      T2DM patients with MCI, which was positively correlated with the total MoCA score
      (r=0.699, P<0.01). Finally, relative to MCI, the left MTG atrophy was also found
      in the T2DM patients with MCI. Our findings suggest that MTG atrophy was
      associated with an increased risk for MCI in T2DM patients. The brain structural
      changes in many brain regions may underlie the transition from normal cognition
      to MCI in T2DM patients. 

PMID- 24434689
TI  - Relationship between Plasmodium falciparum malaria prevalence, genetic diversity
      and endemic Burkitt lymphoma in Malawi.
AB  - Endemic Burkitt lymphoma (eBL) has been linked to Plasmodium falciparum (Pf)
      malaria infection, but the contribution of infection with multiple Pf genotypes
      is uncertain. We studied 303 eBL (cases) and 274 non eBL-related cancers
      (controls) in Malawi using a sensitive and specific molecular-barcode array of 24
      independently segregating Pf single nucleotide polymorphisms. Cases had a higher
      Pf malaria prevalence than controls (64.7% versus 45.3%; odds ratio [OR] 2.1, 95%
      confidence interval (CI): 1.5 to 3.1). Cases and controls were similar in terms
      of Pf density (4.9 versus 4.5 log copies, p = 0.28) and having >=3 non-clonal
      calls (OR 2.7, 95% CI: 0.7-9.9, P = 0.14). However, cases were more likely to
      have a higher Pf genetic diversity score (153.9 versus 133.1, p = 0.036), which
      measures a combination of clonal and non-clonal calls, than controls. Further
      work is needed to evaluate the possible role of Pf genetic diversity in the
      pathogenesis of endemic BL. 

PMID- 24434690
TI  - Prostate cancer incidence in males with Lynch syndrome.
AB  - PURPOSE: An increased risk of prostate cancer is currently not considered a part
      of the Lynch syndrome spectrum. The purpose of this study was to retrospectively
      examine prostate cancer incidence in the Lynch syndrome cohort at the Ohio State
      University in comparison with that in the general population. METHODS: We
      included all males diagnosed with Lynch syndrome from June 1998 to June 2012 at
      the Ohio State University and obtained baseline information including cancer
      history. If patients had not been seen in the 12 months before June 2012, they
      were contacted to document changes in their cancer history. We compared prostate
      cancer incidence among the Lynch syndrome families with that of the general
      population by using the Surveillance, Epidemiology, and End RESULTS registry 1999
      2009. RESULTS: Of the 188 males identified with Lynch syndrome, 11 males were
      diagnosed with prostate cancer during the study period. The ratio of observed to
      expected numbers of prostate cancer cases resulted in a standardized rate ratio
      of 4.87 (95% confidence interval: 2.43-8.71). Impaired mismatch repair expression
      and microsatellite instability were seen in one out of two prostate cancer
      specimens available for testing. CONCLUSION: Males with Lynch syndrome had a
      nearly fivefold increased risk of developing prostate cancer but did not appear
      to have earlier onset or a more aggressive phenotype.

PMID- 24434691
TI  - Attitudes of parents toward the return of targeted and incidental genomic
      research findings in children.
AB  - PURPOSE: We describe parental attitudes toward the return of targeted and
      incidental genomic research results in the setting of high-risk pediatric cancer
      and inherited childhood diseases. METHODS: A validated 36-item questionnaire was
      mailed to participants in three large-scale genome research consortia examining
      attitudes toward receipt of genomic research results and the influence of
      certainty, severity, and onset of the condition, in addition to responsibilities
      to extended family and provision of results even after death of the proband.
      RESULTS: Of the 563 participants who were sent questionnaires, 362 (64%)
      responded. Most of them stated a positive right to receive results related to the
      target condition (97%) or to incidental findings (86%); no difference was found
      in results between participants with cancer and those with orphan diseases.
      Furthermore, 92% indicated that genomic research for childhood-onset conditions
      should occur. The majority wanted incidental results predicting susceptibility
      even to untreatable fatal conditions (83%), to multiple conditions (87%), or to
      those with uncertain impact (70%). Most felt sibling genomic results showing
      serious conditions, whether treatable (93%) or not (88%), and/or results
      discovered after death of the proband should be shared with family (74%).
      CONCLUSION: Many parents of children in pediatric genomic research indicated a
      strong desire to receive a broader range of results than is described in
      consensus recommendations. Clear delineation of what will be offered should be
      established at the time of consent.

PMID- 24434692
TI  - Charcot-Marie-Tooth disease: an overview of genotypes, phenotypes, and clinical
      management strategies.
AB  - Charcot-Marie-Tooth (CMT) disease, which encompasses several hereditary motor and
      sensory neuropathies, is one of the most common neuromuscular disorders. Our
      understanding of the molecular genotypes of CMT and the resultant clinical and
      electrophysiological phenotypes has increased greatly in the past decade.
      Characterized by electrodiagnostic studies into demyelinating (type 1) and axonal
      (type 2) forms, subsequent genetic testing often provides an exact diagnosis of a
      specific subtype of CMT. These advancements have made diagnostic paradigms fairly
      straightforward. Still, the nature and extent of neuromuscular disability is
      often complex in persons with CMT, and no curative treatments are yet available.
      Genotypically homologous animal models of CMT have improved exploration of
      disease-modifying treatments, of which molecular genetic manipulation and stem
      cell therapies appear to be the most promising. Research is also needed to
      develop better rehabilitative strategies that may limit disease burden and
      improve physical performance and psychosocial integration. Clinical management
      should be multidisciplinary, including neurologists, physiatrists,
      neurogeneticists, neuromuscular nurse practitioners, and orthopedists, along with
      physical and occupational therapists, speech-language pathologists, orthotists,
      vocational counselors, social workers, and other rehabilitation clinicians. Goals
      should include maximizing functional independence and quality of life while
      minimizing disability and secondary morbidity. 

PMID- 24434693
TI  - Synthesis and photophysical property studies of the 2,6,8-triaryl-4
      (phenylethynyl)quinazolines.
AB  - The 2-aryl-6,8-dibromo-4-chloroquinazolines derived from the 2-aryl-6,8
      dibromoquinazolin-4(3H)-ones were subjected to the Sonogashira cross-coupling
      with terminal acetylenes at room temperature to afford novel 2-aryl-6,8-dibromo-4
      (alkynyl)quinazoline derivatives. Further transformation of the 2-aryl-6,8
      dibromo-4-(phenylethynyl)quinazolines via Suzuki-Miyaura cross-coupling with
      arylboronic acids occurred without selectivity to afford the corresponding 2,6,8
      triaryl-4-(phenylethynyl)quinazolines. The absorption and emission properties of
      these polysubstituted quinazolines were also determined. 

PMID- 24434694
TI  - Pestalafuranones F-J, five new furanone analogues from the endophytic fungus
      Nigrospora sp. BM-2.
AB  - Five new 2(5H)-furanone-type derivatives, pestalafuranones F-J (compounds 3-7),
      together with two known compounds, pestalafuranones A (1) and B (2), were
      isolated from the ethyl acetate extract from the fermentation broth of the
      endophytic fungus Nigrospora sp. BM-2 in a hypersaline medium. The structures of
      these metabolites were elucidated by EIMS, HREIMS and NMR spectroscopic data.
      Compounds 1-7 exhibited no cytotoxic activities against the MDA-MB-231 and Caski
      cancer cell lines. 

PMID- 24434695
TI  - Diastereoselective three-component reactions of chiral nickel(II) glycinate for
      convenient synthesis of novel alpha-amino-beta-substituted-gamma,gamma
      disubstituted butyric acids.
AB  - The convenient, high yielding and diastereoselective synthesis of alpha-amino
      beta-substituted-gamma,gamma-disubstituted butyric acid derivatives was carried
      out by a three-component tandem reaction of a chiral equivalent of nucleophilic
      glycine. The reaction was performed smoothly under mild conditions and enabled
      the construction of two or three adjacent chiral centers in one step, thus
      affording a novel and convenient route to alpha-amino-beta-substituted
      gamma,gamma-disubstituted butyric acid derivatives. 

PMID- 24434696
TI  - A stable synergistic microbial consortium for simultaneous azo dye removal and
      bioelectricity generation.
AB  - Microbial species coexist in natural or engineered settings, where they encounter
      extensive competition and cooperation. Interactions occurring through metabolite
      exchange or direct contact might be important in establishment of functional
      biodegradation consortium. Understanding these interactions can facilitate
      manipulation of selected communities and exploitation of their capacity for
      specific industrial applications. Here, a simple dual-species consortium
      (Pseudomonas putida and Shewanella oneidensis) was established for examining
      simultaneous Congo red bioremediation in planktonic culture and power generation
      in anode biofilms. Compared to mono-species cultures, co-cultures generated
      higher current densities and could concurrently degrade Congo red over 72h.
      Disabling the large secreted adhesion protein, LapA, of P. putida greatly
      enhanced S. oneidensis biofilm formation on the anode, which increased power
      generation in co-cultures. This demonstrates simultaneous control of specific
      planktonic and biofilm communities could be effective in manipulating microbial
      communities for targeted applications. 

PMID- 24434697
TI  - Biodiesel production from yeast Cryptococcus sp. using Jerusalem artichoke.
AB  - Jerusalem artichoke was investigated as a cheap substrate for the heterotrophic
      production using a lab yeast strain Cryptococcus sp. Using Response Surface
      Method, 54.0% of fructose yield was achieved at 12% of dried Jerusalem artichoke
      powder, 0.57% of nitric acid concentration, 117 degrees C of reaction
      temperature, and 49min of reaction time. At this optimal condition, nitric acid
      showed the best catalytic activity toward inulin hydrolysis and also the
      resulting fructose hydrolyte supported the highest microbial growth compared with
      other acids. In addition, lipid productivity of 1.73g/L/d was achieved, which is
      higher than a defined medium using pure fructose as a substrate. Lipid quality
      was also found to be generally satisfactory as a feedstock for fuel,
      demonstrating Jerusalem artichoke could indeed be a good and cheap option for the
      purpose of biodiesel production. 

PMID- 24434698
TI  - Effect of presence of cellulose in the freshwater sediment on the performance of
      sediment microbial fuel cell.
AB  - The performance of sediment microbial fuel cells (SMFCs) was evaluated in the
      presence of cellulose in the aquaculture pond sediment as 2% (w/w) in SMFC-2, 4%
      in SMFC-3 and without adding cellulose in SMFC-1. From aquaculture water, average
      chemical oxygen demand (COD) and total nitrogen (TN) removal efficiencies of
      80.6+/-0.3% and 83.0+/-0.01% were obtained in SMFC-1, 88.2+/-0.5% and 89.6+/-0.8%
      in SMFC-2 and 83.1+/-0.3% and 64.5+/-1.6% in SMFC-3, respectively. During the
      complete experimental period, acetic acid was the only short chain fatty acid
      detected in all three SMFCs. Sediment organic matter removal in SMFC-1, SMFC-2
      and SMFC-3 were 16%, 22% and 18.6%, respectively. SMFCs demonstrated effective
      cellulose degradation from aquaculture pond sediment and maintained the oxidized
      sediment top layer favourable for aquaculture. 

PMID- 24434699
TI  - Acid tolerance response (ATR) of microbial communities during the enhanced
      biohydrogen process via cascade acid stress.
AB  - Enhanced biohydrogen production via cascade acid stress on microbial communities,
      structure patterns of the microbial communities revealed by PLFAs, and the
      succession of biohydrogen related species against cascade acid stress were all
      investigated. It was found that hydrogen production could be improved from 48.7
      to 79.4mL/gVS after cascade acid stress. In addition, the Gram negative (G(-))
      bacteria were found to be more tolerant to organic acids than those of the Gram
      positive (G(+)) bacteria, regardless of the dominance of G(+) bacteria within the
      microbial communities. Moreover, Clostridium butyricum, Clostridium aciditolerans
      and Azospira oryzae, were proved to be enriched, and then might play
      indispensable roles for the enhanced biohydrogen production after cascade acid
      stress, as which were responsible for the biohydrogen accumulation, acid
      tolerance and nitrogen removal, respectively. 

PMID- 24434700
TI  - Metabolic studies of temperature control strategy on poly(gamma-glutamic acid)
      production in a thermophilic strain Bacillus subtilis GXA-28.
AB  - A thermophilic strain Bacillus subtilis GXA-28 with capability of gamma-PGA
      production was characterized, and its product was identified. The effect of
      temperatures on cell growth, gamma-PGA yield and molecular weight were
      investigated. Results showed that gamma-PGA yield reached 19.92g/L at 45 degrees
      C with a high productivity of 0.91g/L/h, and the molecular weight reached
      3.03*10(6)Da. Then, the flux distribution and the key enzyme activities at 2
      oxoglutarate branch under specified temperature were determined to illustrate the
      possible metabolic mechanism contributing to the improved gamma-PGA production.
      Results indicated that the fluxes from iso-citrate to 2-oxoglutarate and from 2
      oxoglutarate to glutamate were increased with high activity of isocitrate
      dehydrogenase and glutamate dehydrogenase, which led to enhance gamma-PGA
      production. This work firstly employed temperature control strategy to improve
      gamma-PGA production, and provided novel information on the metabolic mechanism
      of gamma-PGA biosynthesis in Bacillus species. 

PMID- 24434701
TI  - Recovering/concentrating of hemicellulosic sugars and acetic acid by
      nanofiltration and reverse osmosis from prehydrolysis liquor of kraft based
      hardwood dissolving pulp process.
AB  - This work investigated the feasibility of recovering and concentrating sugars and
      acetic acid (HAc) from prehydrolysis liquor (PHL) of the kraft-based dissolving
      pulp process prior to fermentation of hemicellulosic sugars, by the combination
      of activated carbon adsorption, nanofiltration (NF) and reverse osmosis (RO)
      processes. To reduce the fouling PHL was subjected to adsorption on activated
      carbon, then the treated PHL (TPHL) passed through a nanofiltration (NF DK)
      membrane to retain the sugars, and the permeate of acetic acid rich solution was
      passed through a reverse osmosis membrane (RO SG). It was found that for NF
      process sugars were concentrated from 48 to 227g/L at a volume reduction factor
      (VRF) of 5 while 80 to 90% of acetic acid was permeated. For the reverse osmosis
      process, 68% of acetic acid retention was achieved at pH 4.3 and 500 psi pressure
      and the HAc concentration increased from 10 to 50g/L. 

PMID- 24434702
TI  - Efficient conversion of brown grease produced by municipal wastewater treatment
      plant into biofuel using aluminium chloride hexahydrate under very mild
      conditions.
AB  - Wastes produced by oil/water separation at the wastewater treatment plant of Bari
      West (Southern Italy) were taken, characterized and converted. About 12% of this
      material was composed of greases, mainly made of free fatty acids (50%) and soaps
      (34%), and was easily separable by the aqueous phase through a hot
      centrifugation. After chemical activation of this fatty fraction, a direct
      esterification was carried out under very mild conditions (320K and atmospheric
      pressure), converting more than 90% of the original free fatty acids into the
      respective methyl esters in less than 4h, by using AlCl3.6H2O. The activation
      energy correlated to the use of this catalyst was also calculated
      (Eaest=43.9kJmol(-1)). The very low cost of the biodiesel produced (0.45?L(-1))
      and the associated relevant specific energy (5.02MJ kgFAMEs(-1)) make such a
      process a really sustainable and effective example of valorization of a waste. 

PMID- 24434703
TI  - Enhanced cell growth by nanoengineering zirconia to stimulate electrostatic
      fibronectin activation.
AB  - We address the enhanced bone growth on designed nanocrystalline zirconia implants
      as reported by in vivo experiments. In vitro experiments demonstrate that the
      activation of adhesive proteins on nanoengineered zirconia stimulates cell
      adhesion and growth as shown by confocal microscopy. Fibrillar fibronectin (FN)
      forms a matrix assembly on the nanostructured surface in the cell adhesion
      process. We discuss the importance of FN dimer activation due to its
      immobilization on the designed nanocrystalline ZrO2 implant fabricated by ion
      beam assisted deposition. The Monte-Carlo analysis indicates that FN activation
      on the surface can be promoted by selective electrostatic interactions between
      negatively charged ZrO2 surface patches and oppositely charged FN domains.

PMID- 24434704
TI  - A word from the Editor on the special issue on 'Public Engagement'.

PMID- 24434705
TI  - Why should we promote public engagement with science?
AB  - This introductory essay looks back on the two decades since the journal Public
      Understanding of Science was launched. Drawing on the invited commentaries in
      this special issue, we can see narratives of continuity and change around the
      practice and politics of public engagement with science. Public engagement would
      seem to be a necessary but insufficient part of opening up science and its
      governance. Those of us who have been involved in advocating, conducting and
      evaluating public engagement practice could be accused of over-promising. If we,
      as social scientists, are going to continue a normative commitment to the idea of
      public engagement, we should therefore develop new lines of argument and
      analysis. Our support for the idea of public engagement needs qualifying, as part
      of a broader, more ambitious interest in the idea of publicly engaged science. 

PMID- 24434706
TI  - Engaging with the political imaginaries of science: Near misses and future
      targets.
AB  - The current economic and financial crisis is also a political crisis that
      requires a rethinking of public engagement with science. In the past, the
      dominant focus of science, technology and society (STS) has led to a blind spot:
      political understanding and engagement of policy-makers and politicians with
      science, which is an integral part of any public engagement. Arguably, it is
      bound to and emerges from what Ezrahi calls collective political imaginaries.
      These are necessary fictions, which are causative and performative. In crude
      form, they manifest themselves in short-term impact measurements of every unit of
      scientific activity with citizens as the fictitious ultimate beneficiaries. In
      the future, STS can gain from coming up with a workable definition of the public
      interest with a focus on the public value of science. It can investigate
      collective imaginaries as they emerge from interactions with new media. As
      necessary fictions they may hold answers we never imagined them to hold. 

PMID- 24434707
TI  - A mirror for science.
AB  - Early conceptions of the public understanding of science suffered from a narrow
      framing of what science means and a presumption that science is divided from its
      publics by walls of ignorance and indifference. Those assumptions amplified
      misunderstanding and led to faulty policies. It is time to reopen each element in
      the term "public understanding of science" to renewed reflection. This journal
      can advance that goal by encouraging research on actual rather than imagined
      public responses to science, on representations of science in the public sphere,
      and on interactions between science, technology and society.

PMID- 24434708
TI  - Reflecting on public engagement and science policy.
AB  - This article presents a personal reflection on the evolution of thinking about
      public engagement with science in the UK, with a particular emphasis on the
      experience with nanotechnology. 

PMID- 24434709
TI  - Unbalanced progress: The hard road from science popularisation to public
      engagement with science in China.
AB  - This article critically traces the development of science communication in China
      in the past 30 years. While confirming the tremendous progress Chinese science
      communicators have achieved in popularising science, it argues that the deficit
      model-based popularisation effort cannot meet the diversifying demands on science
      in Chinese society. Citing both recent science and technology controversies and
      active public participation in science pilot initiatives in China, this article
      concludes that science communication efforts in the country must be focused on
      constructive dialogues and public engagement with science.

PMID- 24434710
TI  - On the limits of public engagement for the governance of emerging technologies.

PMID- 24434711
TI  - On the weakness of strong ties.
AB  - Departing from experiences at a recent conference on Science in Dialogue, the
      paper reflects on the significance of the closure of the Danish Board of
      Technology as a government funded institution. It is argued that the lack of
      active support from the Danish public might be an unanticipated consequence of
      the Board's successful institutionalisation. 

PMID- 24434712
TI  - From 'trust us' to participatory governance: Deliberative publics and science
      policy.
AB  - The last 20 years have seen a shift from the view that publics need to be
      educated so that they trust science and its governance to the recognition that
      publics possess important local knowledge and the capacity to understand
      technical information sufficiently to participate in policy decisions. There are
      now a variety of approaches to increasing the role of publics and advocacy groups
      in the policy and governance of science and biotechnology. This article considers
      recent experiences that demonstrate that it is possible to bring together those
      with policy making responsibility and diverse publics to co-produce policy and
      standards of practice that are technically informed, incorporate wide social
      perspectives and explicitly involve publics in key decisions. Further, the
      process of deliberation involving publics is capable of being incorporated into
      governance structures to enhance the capacity to respond to emerging issues with
      levels of public engagement that are proportionate to the issues. 

PMID- 24434713
TI  - Building the capacity for public engagement with science in the United States.
AB  - This paper reviews efforts of the Center for Nanotechnology in Society at Arizona
      State University (CNS-ASU) to begin to build capacity for public engagement with
      science in the United States. First, the paper sets a context in the US of the
      current challenges to democracy and for science. It then reviews the literature
      on the accomplishments of the National Citizens' Technology Forum (NCTF) on
      nanotechnology and human enhancement, held in 2008, as well as some caveats that
      emerged from that enterprise. It concludes with a brief discussion of two kinds
      of activities - participation in the World Wide Views process organized by the
      Danish Board of Technology, and methodological innovations that include more
      concrete and experiential modes of engagement - that have spun off from the NCTF.

PMID- 24434714
TI  - Further disorientation in the hall of mirrors.
AB  - This paper reviews some changes and continuities in science-society relations
      which have shaped this journal's birth and development. I argue that the main
      focus on publics has been developed with insufficient primary attention to
      problematising what is meant by 'science' in its variable public forms, including
      discourses. We cannot understand 'publics' in relation to 'science', unless we
      also ask, searchingly, what is it that they experience as such, in all its
      multiple self-contradictions and confusions? Thus I reiterate the point made in
      the inaugural issue, still neglected in mainstream science and policy, that
      'science' needs to be critically addressed in several dimensions, as part of
      public understanding of science research. First, instrumental pragmatic
      scientific meanings, useful in their own parochial situations, should not be
      given automatic sovereignty in public issues. Second, public concerns where they
      exist should not be interpreted and judged against this presumptively entrenched
      scientistic normative baseline.

PMID- 24434715
TI  - From deficit to democracy (re-visited).
AB  - Taking as its frame the last twenty years of policy-making and academic
      discussion regarding public engagement with science (PES), this short article
      offers a personal evaluation of the balance between failure and achievement, and
      reflects upon some of the other contributions to the special issue. Put in the
      most general terms, have we been moving forwards or in circles? The persistence
      of public engagement efforts and existence of constructive science-social science
      collaborations are noted. However, the ambiguous character of the institutional
      embrace of social science and the instrumental role accorded to PES research
      remain as significant issues. Following a retrospective discussion of the
      'deficit' model of science-public relations, some conclusions are drawn
      concerning the future needs of both reflective practice and practical reflection.

PMID- 24434716
TI  - Impact of legislation on passive smoking in Spain.
AB  - BACKGROUND: In 2005, the Spanish government approved Law 28/2005 on health
      measures against smoking; this was amended in 2010 by Law 42/2010. OBJECTIVE: The
      purpose of this study was to assess the impact of these laws on passive smoking.
      METHODS: Three epidemiological studies were conducted on a representative sample
      of the population via telephone surveys. The first was conducted prior to the
      first law coming into force, the second a year after its approval and the third a
      year after the approval of the second. RESULTS: Six thousand eight hundred people
      were surveyed in 2005, 3,289 in 2007 and 3,298 in 2011. The first survey showed
      that 49.5% of nonsmokers were exposed to second-hand smoke (SHS) while by 2007,
      following the introduction of Law 28/2005, this exposure had been reduced to
      37.9% (results previously published in 2008). The 2011 survey, conducted
      following the introduction of Law 42/2010, showed that just 21% of people were
      exposed. These data indicate that overall exposure to SHS was reduced by 22%
      between 2005 and 2007 and by a further 16.9% between 2007 and 2011. The overall
      impact of Law 42/2010 is estimated to be around 44% and Law 28/2005 around 22%.
      CONCLUSION: Legislation introduced in Spain has markedly reduced the exposure of
      nonsmokers to SHS.

PMID- 24434717
TI  - Estimation of ligand affinity constants for receptor states in functional studies
      involving the allosteric modulation of G protein-coupled receptors: implications
      for ligand bias.
AB  - INTRODUCTION: The affinity constants of a ligand for active and inactive states
      of a receptor ultimately determine its capacity to activate downstream signaling
      events. In this report, we describe a reverse-engineering strategy for estimating
      these microscopic constants. METHODS: Our approach involves analyzing responses
      measured downstream in the signaling pathway of a G protein-coupled receptor
      under conditions of allosteric modulation and reduced receptor expression or
      partial receptor inactivation. The analysis also yields estimates of the
      isomerization constant of the unoccupied receptor, the sensitivity constant of
      the signaling pathway, and the more empirical parameters of the receptor
      population including the observed affinities and efficacies of allosteric and
      orthosteric ligands - including inverse agonists - and the efficacy of the
      unoccupied receptor (i.e., constitutive activity). RESULTS AND DISCUSSION: We
      validate our approach with an analytical proof and by analysis of simulated data.
      We also use our method to analyze data from the literature. We show that the
      values of the microscopic constants of orthosteric and allosteric ligands are
      constant regardless of the allosteric interaction and the nature of the receptor
      signaling pathway as long as the same active state mediates the response. Our
      analysis is useful for quantifying probe-dependent allosteric interactions and
      the selectivity of agonists for different signaling pathways. Knowing the
      isomerization constant and sensitivity constant of a signaling pathway in a given
      cell line or tissue preparation enables future investigators to estimate the
      affinity constants of agonists for receptor states simply through analysis of
      their concentration-response curves. Our approach also provides a means of
      validating in silico estimates of ligand affinity for crystal structures of
      active and inactive states of the receptor.

PMID- 24434718
TI  - LAMP3 is involved in tamoxifen resistance in breast cancer cells through the
      modulation of autophagy.
AB  - Lysosome-associated membrane protein 3 (LAMP3) is a member of the LAMP-family of
      proteins, which are involved in the process of autophagy. Autophagy is induced by
      tamoxifen in breast cancer cells and may contribute to tamoxifen resistance. In
      this study, the significance of LAMP3 for tamoxifen resistance in breast cancer
      was examined. The methods employed included use of clonogenic assays to assess
      the survival of MCF7 breast cancer cells with LAMP3 knockdown after tamoxifen
      treatment and of quantitative real-time PCR of LAMP3 to evaluate its predictive
      value for first-line tamoxifen treatment in patients with advanced breast cancer.
      Results show that tamoxifen treatment of MCF7 cells induced LAMP3 mRNA
      expression. LAMP3 knockdown in these cells increased tamoxifen sensitivity.
      Evaluation of expression of the autophagy markers, LC3B and p62, after LAMP3
      knockdown showed increased expression levels, indicating that cells with LAMP3
      knockdown have a suppressed ability to complete the autophagic process. In
      addition, knockdown of autophagy-associated genes resulted in sensitization to
      tamoxifen. Next, tamoxifen-resistant MCF7 cells were cultured. These cells had a
      sevenfold higher LAMP3 mRNA expression, showed elevated basal autophagy levels,
      and could be significantly resensitized to tamoxifen by LAMP3 knockdown. In
      patients treated with first-line tamoxifen for advanced disease (n=304), high
      LAMP3 mRNA expression was associated with shorter progression-free survival
      (P=0.003) and shorter post-relapse overall survival (P=0.040), also in
      multivariate analysis. Together, these results indicate that LAMP3 contributes to
      tamoxifen resistance in breast cancer. Tamoxifen-resistant cells are resensitized
      to tamoxifen by the knockdown of LAMP3. Therefore, LAMP3 may be clinically
      relevant to countering tamoxifen resistance in breast cancer patients. 

PMID- 24434719
TI  - Aromatase inhibitors in the breast cancer clinic: focus on exemestane.
AB  - Breast cancer is the most prevalent type of cancer in women and responsible for
      significant female cancer-related mortality worldwide. In the Western world, over
      80% of breast cancers are hormone-receptor positive for which endocrine therapy
      is administered. The main anti-estrogen treatments in use consist of selective
      estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase
      inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review,
      the focus will lie on exemestane, its clinical use, and its side-effect profile.
      Exemestane is the only third-generation steroidal AI. Its efficacy as a first
      line treatment in metastatic breast cancer has been demonstrated. Therefore,
      exemestane could be considered a valid first-line therapeutic option, but it also
      can be used in second-line or further situations. Exemestane is mostly used as
      part of sequential adjuvant treatment following tamoxifen, but in this setting it
      is also active in monotherapy. Furthermore, this AI has been studied in the
      neoadjuvant setting as presurgical treatment, and even as chemoprevention in high
      risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such
      as endometrial changes and thromboembolic disease but may also cause some
      inconvenient side effects itself. Additionally, there is a lack of total cross
      resistance between exemestane and nonsteroidal AIs as far as their anti-tumoral
      efficacy is concerned; moreover the two classes of AIs display a nontotal
      overlapping toxicity profile. Taking together, exemestane can be considered as a
      useful treatment option at all stages of breast cancer. 

PMID- 24434720
TI  - Mild cognitive impairment in patients with moderate to severe chronic plaque
      psoriasis.
AB  - BACKGROUND: Psoriasis is frequently associated with cardiometabolic comorbidities
      and depression that are risk factors for cognitive impairment. OBJECTIVE: To
      investigate cognitive performance in psoriatic patients. METHOD: Cognitive
      performances were assessed by neuropsychological tests in 41 patients with
      psoriasis and 37 controls. Diagnostic criteria for mild cognitive impairment
      (MCI) were (1) subjective complaint of a memory deficit, confirmed by a relative
      or caregiver, (2) pathological performance on neuropsychological tests
      investigating cognitive domains, (3) normal performance of daily living
      activities and (4) no dementia. Neuroimaging was studied by high-field magnetic
      resonance imaging and cortical thickness analysis. RESULTS: MCI was found in 18
      out of 41 (44%) patients with psoriasis compared to 4 out of 37 (11%) controls (p
      = 0.002). In particular, patients with psoriasis had lower scores in the delayed
      recall of the Rey Auditory Verbal Learning Test (p = 0.04), Backwards Digit Span
      Test (p = 0.002), Weigl's Sorting Test (p = 0.01) and Trail Making Test B (p =
      0.008). In the 7 patients submitted to cortical thickness analysis, a reduction
      in brain thickness in parahippocampal, superior temporal and frontal gyri of the
      left hemisphere was observed. CONCLUSIONS: Patients with psoriasis may have a
      precocious impairment of long-term verbal memory, executive functions and
      attention.

PMID- 24434721
TI  - A Fas-associated via death domain promoter polymorphism (rs10898853, -16C/T) as a
      risk factor for papillary thyroid cancer.
AB  - PURPOSE: To determine whether a Fas-associated via death domain (FADD) promoter
      single-nucleotide polymorphism (SNP) is associated with susceptibility to
      papillary thyroid cancer (PTC) and clinicopathological features of PTC. METHODS:
      To identify a possible association with PTC, 94 patients with PTC and 346 healthy
      controls were recruited. One promoter SNP (rs10898853, -16C/T) was analyzed by
      direct sequencing. Multiple logistic regression models (co-dominant, dominant,
      recessive, and log-additive models) were applied, and odds ratios (ORs), 95%
      confidence intervals (CIs), and p values were calculated. RESULTS: The genotype
      of the promoter SNP (rs10898853) of FADD was found to be significantly associated
      with PTC in the co-dominant model 2 (T/T vs. C/C; p = 0.002, OR = 2.80, 95% CI =
      1.39-5.65), the recessive model (p = 0.003, OR = 2.21, 95% CI = 1.31-3.71), and
      the log-additive model (p = 0.002, OR = 1.71, 95% CI = 1.20-2.44). Allele
      frequency analysis showed that the C allele of rs10898853 was significantly
      associated with an increased risk of PTC (p = 0.002, OR = 1.67, 95% CI = 1.21
      2.32). CONCLUSIONS: Our results suggest that the FADD promoter polymorphism is
      associated with susceptibility to PTC.

PMID- 24434722
TI  - Combustion By-Products and their Health Effects--combustion engineering and
      global health in the 21st century: issues and challenges.
AB  - The 13th International Congress on Combustion By-Products and their Health
      Effects was held in New Orleans, Louisiana from May 15 to 18, 2013. The congress,
      sponsored by the Superfund Research Program, National Institute of Environmental
      Health Sciences, and National Science Foundation, brought together international
      academic and government researchers, engineers, scientists, and policymakers.
      With industrial growth, increased power needs and generation and coal consumption
      and their concomitant emissions, pernicious health effects associated with
      exposures to these emissions are on the rise. This congress provides a unique
      platform for interdisciplinary exchange and discussion of these topics. The
      formation, conversion, control, and health effects of combustion by-products,
      including particulate matter and associated heavy metals, persistent organic
      pollutants, and environmentally persistent free radicals, were discussed during
      the congress. This review will summarize and discuss the implications of the data
      presented. 

PMID- 24434724
TI  - Death by oxymoron? The enigma of heart failure with preserved ejection fraction.

PMID- 24434723
TI  - Glyphosate commercial formulation causes cytotoxicity, oxidative effects, and
      apoptosis on human cells: differences with its active ingredient.
AB  - In the present study, the effects on oxidative balance and cellular end points of
      glyphosate, aminomethylphosphonic acid (AMPA), and a glyphosate formulation (G
      formulation) were examined in HepG2 cell line, at dilution levels far below
      agricultural recommendations. Our results show that G formulation had toxic
      effects while no effects were found with acid glyphosate and AMPA treatments.
      Glyphosate formulation exposure produced an increase in reactive oxygen species,
      nitrotyrosine formation, superoxide dismutase activity, and glutathione (GSH)
      levels, while no effects were observed for catalase and GSH-S-transferase
      activities. Also, G formulation triggered caspase 3/7 activation and hence
      induced apoptosis pathway in this cell line. Aminomethylphosphonic acid exposure
      produced an increase in GSH levels while no differences were observed in other
      antioxidant parameters. No effects were observed when the cells were exposed to
      acid glyphosate. These results confirm that G formulations have adjuvants working
      together with the active ingredient and causing toxic effects that are not seen
      with acid glyphosate. 

PMID- 24434725
TI  - Novel hypoglycaemic agents: considerations in patients with chronic kidney
      disease.
AB  - One of the commonest complications of type 2 diabetes is renal disease. Treatment
      guidelines emphasise the need for tight glycaemic control to reduce the
      development of future complications; however, with the development of renal
      impairment, the benefit of tight glycaemic control must be weighed against the
      potential for adverse effects from drugs or their metabolites which may
      accumulate. In this article, the glucose-lowering drugs used in the management of
      type 2 diabetes are reviewed, with particular emphasis on newer guidelines and
      agents.

PMID- 24434726
TI  - Efficacy of different carrier gases for barrier discharge plasma generation
      compared to chlorhexidine on the survival of Pseudomonas aeruginosa embedded in
      biofilm in vitro.
AB  - Because of its antimicrobial properties, nonthermal plasma could serve as an
      alternative to chemical antisepsis in wound treatment. Therefore, this study
      investigated the inactivation of biofilm-embedded Pseudomonas aeruginosa SG81 by
      a surface barrier-discharged (SBD) plasma for 30, 60, 150 and 300 s. In order to
      optimize the efficacy of the plasma, different carrier gases (argon, argon
      admixed with 1% oxygen, and argon with increased humidity up to approx. 80%) were
      tested and compared against 0.1% chlorhexidine digluconate (CHG) exposure for 600
      s. The antimicrobial efficacy was determined by calculating the difference
      between the numbers of colony-forming units (CFU) of treated and untreated
      biofilms. Living bacteria were distinguished from dead by fluorescent staining
      and confocal laser scanning microscopy. Both SBD plasmas and CHG showed
      significant antimicrobial effects compared to the untreated control. However,
      plasma treatment led to a higher antimicrobial reduction (argon plasma 4.9 log10
      CFU/cm(2), argon with admixed oxygen 3 log10 CFU/cm(2), and with increased gas
      humidity 2.7 log10 CFU/cm(2) after 300 s) compared to CHG. In conclusion, SBD
      plasma is suitable as an alternative to CHG for inactivation of Pseudomonas
      aeruginosa embedded in biofilm. Further development of SBD plasma sources and
      research on the role of carrier gases and humidity may allow their clinical
      application for wound management in the future.

PMID- 24434727
TI  - Para-iliac actinomycetoma presenting as sarcoma, a late complication of
      appendicitis: A case report.
AB  - INTRODUCTION: Actinomycosis is known to mimic several types of neoplasms, leading
      to morbid surgical interventions. PRESENTATION OF CASE: We report the particular
      case of an extensive right para-iliac actinomycetoma presenting as a sarcoma,
      which to our knowledge has not yet been described in the literature, in a patient
      with previous ruptured appendicitis. Thanks to the collaborative work between the
      orthopedic and general surgeons, pathologist and microbiologist, the diagnosis of
      actinomycosis was made pre-operatively, saving this 15-year-old patient from a
      tumor resection protocol. DISCUSSION: Actinomycetomas have often been reported to
      present in the same way as several abdominal and gynecological neoplasms, and on
      rare occasions been described as mimicking other soft-tissue sarcomas, leading to
      unnecessary morbid tumor resection protocols. The most common cause of abdominal
      actinomycosis is perforated appendicitis, and may present several years later.
      CONCLUSION: While faced with a soft tissue mass transgressing tissue planes and
      possibly extending to the region of the right lower quadrant, especially with a
      history of previous perforated appendicitis, one should consider the possibility
      of an abscess caused by pathogens of intestinal origin, including the gram
      positive anaerobe Actinomycosis israelii. Failure to actively search for this
      pathogen, which is not detectable with routine staining techniques and may take
      up to 1-2 weeks to isolate, may lead to unnecessary morbid surgical procedures.

PMID- 24434728
TI  - Rupture of posterior gastric artery after vomiting: A rare cause of acute
      abdomen.
AB  - INTRODUCTION: Spontaneous hemoperitoneum in healthy males is an extremely rare,
      life threatening emergency condition with high mortality and morbidity, if not
      diagnosed and managed early. PRESENTATION OF CASE: We present a 33-year-old male
      who presented with hemoperitoneum following self-induced vomiting. DISCUSSION: To
      suspect and diagnose the condition is a challenge for clinician if ambiguity in
      presentation prevails. CONCLUSION: The most important strategy in management of
      equivocal cases is early surgical exploration to establish the diagnosis and
      treat accordingly.

PMID- 24434729
TI  - Sex differences in connectivity of the subgenual anterior cingulate cortex.
AB  - We previously reported that women exhibit greater heat pain adaptation to a
      prolonged painful stimulus and greater habituation to repeated painful stimuli
      than men. The neural mechanism underlying this sex difference is unknown.
      However, Bingel et al. (2007) have shown that pain habituation after 8 days of
      daily pain testing is associated with an increase in pain-evoked activity of the
      subgenual anterior cingulate cortex (sgACC), suggesting that pain habituation may
      be mediated via connectivity between the sgACC and the descending pain
      antinociceptive system. Therefore, we investigated whether women have stronger
      functional connectivity (FC) and greater structural connectivity (SC) compared to
      men between the sgACC and the descending antinociceptive system. Our analyses
      revealed that (1) women exhibited greater FC between the sgACC and the
      periaqueductal gray (PAG), raphe nucleus, medial thalamus, and anterior
      midcingulate cortex (aMCC) than men; (2) men had stronger sgACC FC with the
      anterior insula and temporoparietal junction than women; (3) women and men
      exhibited comparable SC of the sgACC with the PAG, thalamus, aMCC, anterior
      insula, and amygdala; and (4) men have stronger sgACC SC with the hypothalamus
      than women. These data indicate that brain circuitry in women may provide for
      greater engagement of the descending modulation system mediating pain
      habituation. In contrast, in men, the salience network may be more engaged, which
      could support greater sustained attention to pain, thereby preventing pain
      habituation. Furthermore, the hypothalamus findings suggest a more powerful
      stress and endorphin-based system at play in men than women.

PMID- 24434731
TI  - Letter to the editor.

PMID- 24434730
TI  - Nociception and inflammatory hyperalgesia evaluated in rodents using infrared
      laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion.
AB  - TRPV1 is expressed in a subpopulation of myelinated Adelta and unmyelinated C
      fibers. TRPV1+ fibers are essential for the transmission of nociceptive thermal
      stimuli and for the establishment and maintenance of inflammatory hyperalgesia.
      We have previously shown that high-power, short-duration pulses from an infrared
      diode laser are capable of predominantly activating cutaneous TRPV1+ Adelta
      fibers. Here we show that stimulating either subtype of TRPV1+ fiber in the paw
      during carrageenan-induced inflammation or following hind-paw incision elicits
      pronounced hyperalgesic responses, including prolonged paw guarding. The
      ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates
      TRPV1+ fibers and blocks thermal nociceptive responses in baseline or inflamed
      conditions. Injecting sufficient doses of RTX peripherally renders animals
      unresponsive to laser stimulation even at the point of acute thermal skin damage.
      In contrast, Trpv1-/- mice, which are generally unresponsive to noxious thermal
      stimuli at lower power settings, exhibit withdrawal responses and inflammation
      induced sensitization using high-power, short duration Adelta stimuli. In rats,
      systemic morphine suppresses paw withdrawal, inflammatory guarding, and
      hyperalgesia in a dose-dependent fashion using the same Adelta stimuli. The
      qualitative intensity of Adelta responses, the leftward shift of the stimulus
      response curve, the increased guarding behaviors during carrageenan inflammation
      or after incision, and the reduction of Adelta responses with morphine suggest
      multiple roles for TRPV1+ Adelta fibers in nociceptive processes and their
      modulation of pathological pain conditions.

PMID- 24434732
TI  - Improvement of pain-related self-management for cancer patients through a modular
      transitional nursing intervention: a cluster-randomized multicenter trial.
AB  - Patients' self-management skills are affected by their knowledge, activities, and
      attitudes toward pain management. This trial aimed to test the Self Care
      Improvement through Oncology Nursing (SCION)-PAIN program, a multimodular
      structured intervention to reduce patients' barriers to self-management of cancer
      pain. Two hundred sixty-three patients with diagnosed malignancy, pain>3 days,
      and average pain > or = 3/10 participated in a cluster-randomized trial on 18
      wards in 2 German university hospitals. Patients on the intervention wards
      received, in addition to standard pain treatment, the SCION-PAIN program
      consisting of 3 modules: pharmacologic, nonpharmacologic pain management, and
      discharge management. The intervention was conducted by specially trained cancer
      nurses and included components of patient education, skills training, and
      counseling. Starting with admission, patients received booster sessions every
      third day and one follow-up telephone counseling session within 2 to 3 days after
      discharge. Patients in the control group received standard care. Primary end
      point was the group difference in patient-related barriers to self-management of
      cancer pain (Barriers Questionnaire-BQ II) 7 days after discharge. The SCION-PAIN
      program resulted in a significant reduction of patient-related barriers to pain
      management 1 week after discharge from the hospital: mean difference on BQ II was
      -0.49 points (95% confidence interval -0.87 points to -0.12 points; P=0.02).
      Furthermore, patients showed improved adherence to pain medication; odds ratio
      8.58 (95% confidence interval 1.66-44.40; P=0.02). A post hoc analysis indicated
      reduced average and worst pain intensity as well as improved quality of life.
      This trial reveals the positive impact of a nursing intervention to improve
      patients' self-management of cancer pain.

PMID- 24434733
TI  - A dynamic model of the eye nystagmus response to high magnetic fields.
AB  - It was recently shown that high magnetic fields evoke nystagmus in human subjects
      with functioning vestibular systems. The proposed mechanism involves interaction
      between ionic currents in the endolymph of the vestibular labyrinth and the
      static magnetic field. This results in a Lorentz force that causes endolymph flow
      to deflect the cupulae of the semi-circular canals to evoke a vestibular-ocular
      reflex (VOR). This should be analogous to stimulation by angular acceleration or
      caloric irrigation. We made measurements of nystagmus slow-phase velocities in
      healthy adults experiencing variable magnetic field profiles of up to 7 T while
      supine on a bed that could be moved smoothly into the bore of an MRI machine. The
      horizontal slow-phase velocity data were reliably modelled by a linear transfer
      function incorporating a low-pass term and a high-pass adaptation term. The
      adaptation time constant was estimated at 39.3 s from long exposure trials. When
      constrained to this value, the low-pass time constant was estimated at 13.6 +/-
      3.6 s (to 95% confidence) from both short and long exposure trials. This
      confidence interval overlaps with values obtained previously using angular
      acceleration and caloric stimulation. Hence it is compatible with endolymph flow
      causing a cupular deflection and therefore supports the hypothesis that the
      Lorentz force is a likely transduction mechanism of the magnetic field-evoked
      VOR. 

PMID- 24434734
TI  - Fabrication of [001]-oriented tungsten tips for high resolution scanning
      tunneling microscopy.
AB  - The structure of the [001]-oriented single crystalline tungsten probes sharpened
      in ultra-high vacuum using electron beam heating and ion sputtering has been
      studied using scanning and transmission electron microscopy. The electron
      microscopy data prove reproducible fabrication of the single-apex tips with
      nanoscale pyramids grained by the {011} planes at the apexes. These sharp, [001]
      oriented tungsten tips have been successfully utilized in high resolution
      scanning tunneling microscopy imaging of HOPG(0001), SiC(001) and
      graphene/SiC(001) surfaces. The electron microscopy characterization performed
      before and after the high resolution STM experiments provides direct correlation
      between the tip structure and picoscale spatial resolution achieved in the
      experiments. 

PMID- 24434740
TI  - Cumulative cultural evolution: the role of teaching.
AB  - In humans, cultural transmission occurs usually by cumulative inheritance,
      generating complex adaptive behavioral features. Cumulative culture requires key
      psychological processes (fundamentally imitation and teaching) that are absent or
      impoverished in non-human primates. In this paper we analyze the role that
      teaching has played in human cumulative cultural evolution. We assume that a
      system of cumulative culture generates increasingly adaptive behaviors, that are
      also more complex and difficult to imitate. Our thesis is that, as cultural
      traits become more complex, cumulative cultural transmission requires teaching to
      ensure accurate transmission from one generation to the next. In an increasingly
      complex cultural environment, we consider that individuals commit errors in
      imitation. We develop a model of cumulative cultural evolution in a changing
      environment and show that these errors hamper the process of cultural
      accumulation. We also show that a system of teaching between parents and
      offspring that increases the fidelity of imitation unblocks the accumulation and
      becomes adaptive whenever the gain in fitness compensates the cost of teaching. 

PMID- 24434741
TI  - Evolution of the genetic code through progressive symmetry breaking.
AB  - Evolution of the genetic code in an early RNA world is dependent on the steadily
      improving specificity of the coevolving protein synthesis machinery for codons,
      anticodons, tRNAs and amino acids. In the beginning, there is RNA but the
      machinery does not distinguish yet between the codons, which therefore all encode
      the same information. Synonymous codons are equivalent under a symmetry group
      that exchanges (permutes) the codons without affecting the code. The initial
      group changes any codon into any other by permuting the order of the bases in the
      triplet as well as by replacing the four RNA bases with each other at every codon
      position. This group preserves the differences between codons, known as Hamming
      distances, with a 1-distance corresponding to a single point mutation. Stepwise
      breaking of the group into subgroups divides the 64 codons into progressively
      smaller subsets - blocks of equivalent codons under the smaller symmetry groups,
      with each block able to encode a different message. This formalism prescribes how
      the evolving machinery increasingly differentiates between codons. The model
      indicates that primitive ribosomes first identified a unique mRNA reading frame
      to break the group permuting the order of the bases and subsequently enforced
      increasingly stringent codon-anticodon basepairing rules to break the subgroups
      permuting the four bases at each codon position. The modern basepairing rules
      evolve in five steps and at each step the number of codon blocks doubles. The
      fourth step generates 16 codon blocks corresponding with the 16 family boxes of
      the standard code and the last step splits these boxes into 32 blocks of commonly
      two, but rarely one or three, synonymous codons. The evolving codes transmit at
      most one message per codon block and as the number of messages increases so does
      the specificity of the code and of protein synthesis. The selective advantage
      conferred by better functioning proteins drives the symmetry breaking process.
      Over time paralogous tRNA evolution expands the anticodon repertoire, which is
      divided into anticodon blocks matching the codon blocks under the stage-specific
      ribosomal basepairing rules. Contemporaneously an expanding family of primitive
      aminoacyl-tRNA synthetases (aaRSs) divides the tRNA diversities into various
      different and overlapping subsets: each aaRS accepts some tRNAs but rejects all
      others and several aaRSs may accept the same tRNA species. Selection favoring
      less ambiguous codes eliminates these overlaps and also imposes the ribosomal
      anticodon block division as ambiguity arises when different aaRSs accept tRNAs of
      the same anticodon block. Only when the tRNAs of one or several anticodon blocks
      are accepted by a unique aaRS does the code become specific. This coding pattern
      is observed in the standard code and the evolution of amino acid assignments by
      primitive aaRSs onto tRNAs is traced back via tRNA trees that picture a gradual
      division of tRNA diversities into blocks with increasingly specific amino acid
      assignments. Symmetry breaking combined with continuous selection for codes
      carrying more information evolves increasingly specific codes and efficiently
      traverses an immense space of all possible codes (>10(84)) to give rise to the
      standard code. 

PMID- 24434742
TI  - Modelling the coupling between intracellular calcium release and the cell cycle
      during cortical brain development.
AB  - Most neocortical neurons formed during embryonic brain development arise from
      radial glial cells which communicate, in part, via ATP mediated calcium signals.
      Although the intercellular signalling mechanisms that regulate radial glia
      proliferation are not well understood, it has recently been demonstrated that ATP
      dependent intracellular calcium release leads to an increase of nearly 100% in
      overall cellular proliferation. It has been hypothesised that cytoplasmic calcium
      accelerates entry into S phase of the cell cycle and/or acts to recruit otherwise
      quiescent cells onto the cell cycle. In this paper we study this cell cycle
      acceleration and recruitment by forming a differential equation model for ATP
      mediated calcium-cell cycle coupling via Cyclin D in a single radial glial cell.
      Bifurcation analysis and numerical simulations suggest that the cell cycle period
      depends only weakly on cytoplasmic calcium. Therefore, the accelerative impact of
      calcium on the cell cycle can only account for a small fraction of the large
      increase in proliferation observed experimentally. Crucially however, our
      bifurcation analysis reveals that stable fixed point and stable limit cycle
      solutions can coexist, and that calcium dependent Cyclin D dynamics extend the
      oscillatory region to lower Cyclin D synthesis rates, thus rendering cells more
      susceptible to cycling. This supports the hypothesis that cycling glial cells
      recruit quiescent cells (in G0 phase) onto the cell cycle, via a calcium
      signalling mechanism, and that this may be the primary means by which calcium
      augments proliferation rates at the population scale. Numerical simulations of
      two coupled cells demonstrate that such a scenario is indeed feasible. 

PMID- 24434743
TI  - Effect of food insecurity on chronic kidney disease in lower-income Americans.
AB  - BACKGROUND: The relation of food insecurity (inability to acquire nutritionally
      adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined
      whether food insecurity is associated with prevalent CKD among lower-income
      individuals in both the general US adult population and an urban population.
      METHODS: We conducted cross-sectional analyses of lower-income participants of
      the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n =
      9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span
      (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires
      and CKD was defined by reduced estimated glomerular filtration rate or
      albuminuria; adjustment was performed with multivariable logistic regression.
      RESULTS: In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7%
      for the high, marginal, and no food insecurity groups, respectively. Analyses
      adjusting for sociodemographics and smoking status revealed high food insecurity
      to be associated with greater odds of CKD only among participants with either
      diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity
      groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age
      adjusted CKD prevalence was 5.9 and 4.6% for those with and without food
      insecurity, respectively (p = 0.33). Food insecurity was associated with a trend
      towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of
      effect modification across diabetes, hypertension, or obesity subgroups.
      CONCLUSION: Food insecurity may contribute to disparities in kidney disease,
      especially among persons with diabetes or hypertension, and is worthy of further
      study.

PMID- 24434745
TI  - Evaluation of several multiple diglycolamide-functionalized calix[4]arene ligands
      for the isolation of carrier free 90Y from 90Sr.
AB  - Several diglycolamide-functionalized calix[4]arenes containing four and eight
      diglycolamide (DGA) moieties were evaluated for their relative extraction
      efficiencies towards Y(III) and Sr(II). Ligands containing four DGA units with n
      propyl, iso-pentyl, and n-octyl groups at the amidic N atom adjacent to the
      calix[4]arene skeleton showed efficient extraction of Y(III) from 3M HNO3. The
      extraction of Sr(II) was poor in all cases in the entire acidity range (0.1-6M
      HNO3) studied. The ligands with a hydrogen atom and an n-propyl group at the
      concerning amidic N atom showed a very high separation efficiency as reflected in
      separation factor (S.F.=DY/DSr) values in the range of 10(5)-10(6). A method was
      developed for the separation of carrier-free (90)Y from a (90)Y-(90)Sr mixture
      involving consecutive extraction-stripping cycles. The product purity was checked
      using half-life measurements. Two consecutive cycles of extraction and stripping
      were found to be sufficient for obtaining pure (90)Y. The results obtained in the
      present studies were compared with those obtained previously using analogous
      ligands such as TODGA (N,N,N',N'-tetraoctyl diglycolamide), T2EHDGA (N,N,N',N'
      tetra-2-ethylhexyl diglycolamide), and PC-88A (bis(2-ethylhexyl) phosphonic
      acid). 

PMID- 24434744
TI  - PACAP in the BNST produces anorexia and weight loss in male and female rats.
AB  - Recent gene association studies have implicated pituitary adenylate cyclase
      activating peptide (PACAP) systems in several psychiatric disorders associated
      with stressor exposure, and we have argued that many of the behavioral
      consequences of repeated stressor exposure may depend on the expression of PACAP
      in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of
      the activation of stress systems can be anorexia and subsequent weight loss, and
      both the activation of central PACAP systems as well as neuronal activity in the
      BNST have also been associated with anorexic states in rodents. Hence, we
      investigated the regulation of food and water intake and weight loss following
      BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well
      as food and water intake in the first 24 h following infusion. Because different
      BNST subregions differentially regulate stress responding, we further examined
      the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST
      PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion
      resulted in weight loss. PACAP38 infused into the lateral ventricles did not
      alter weight, suggesting that the effects of BNST-infused PACAP were not mediated
      by leakage into the ventricular system. These data suggest that PACAP receptor
      activation in posterior BNST subregions can produce anorexia and weight loss, and
      corroborate growing data implicating central PACAP activation in mediating the
      consequences of stressor exposure. 

PMID- 24434746
TI  - Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.
AB  - Metastatic melanoma often relapses despite cytotoxic treatment, and hence the
      understanding of melanoma tumor repopulation is crucial for improving our current
      therapies. In this study, we aim to define the role of caspase 3 in melanoma
      tumor growth after cytotoxic therapy. We examined a paradigm-changing hypothesis
      that dying melanoma cells undergoing apoptosis during cytotoxic treatment
      activate paracrine signaling events that promote the growth of surviving tumor
      cells. We propose that caspase 3 has a key role in the initiation of the release
      of signals from dying cells to stimulate melanoma tumor growth. We created a
      model for tumor cell repopulation in which a small number of luciferase-labeled,
      untreated melanoma cells are seeded onto a layer of a larger number of unlabeled,
      lethally treated melanoma cells. We found that dying melanoma cells significantly
      stimulate the growth of living melanoma cells in vitro and in vivo. Furthermore,
      we observed that caspase 3 gene knockdown attenuated the growth-stimulating
      effect of irradiated, dying cells on living melanoma cell growth. Finally, we
      showed that caspase 3-mediated dying melanoma cell stimulation of living cell
      growth involves secreted prostaglandin E2 (PGE2). Our study therefore suggests a
      counterintuitive strategy to inhibit caspase 3 for therapeutic gain in melanoma
      treatment. 

PMID- 24434748
TI  - Randomized, within-patient, clinical trial comparing fluorine-synthetic fiber
      socks with standard cotton socks in improving plantar pustulosis.
AB  - BACKGROUND/AIMS: Rubbing the skin may influence the persistence of pustulosis
      over time. The aim of this study was to assess the impact of a new fabric made
      with fluorine-synthetic fiber in improving plantar pustulosis. METHODS: A total
      of 17 patients were randomized to receive on one side a sock made of fluorine
      synthetic fiber and on the other a sock made of cotton fabric for 4 weeks. The
      main outcome was the percentage reduction of lesional area at week 4. RESULTS:
      The median lesion reduction at week 4 was 42.6% in the fluorine-synthetic fiber
      arm and 2.7% in the cotton arm (p = 0.148). Among secondary outcomes, the overall
      reduction over time in the treated areas was significantly in favor of the
      fluorine-synthetic fiber arm (p = 0.045) as well as the perception of the disease
      by the patient (p = 0.025). CONCLUSION: Despite the fact that the primary outcome
      was not reached, there was a tangible reduction in the extension of the treated
      areas and in the perception of the disease by the patient.

PMID- 24434749
TI  - Aquagenic wrinkling of the palms and cystic fibrosis: an Italian study with
      controls and genotype-phenotype correlations.
AB  - AIMS: The primary aim was to determine the prevalence of aquagenic wrinkling of
      the palms (AWP) in patients with cystic fibrosis (CF) compared to controls, and
      secondarily to evaluate genotype-phenotype correlations among CF subjects found
      to have AWP. METHODS: Fifty-eight patients with CF underwent a hand immersion
      test in tap water. Twenty-three of their CF carrier relatives and 7 subjects with
      a negative genetic test for CF were recruited as controls. Secondary analyses
      explored associations with genotype, pulmonary function, and sweat electrolyte
      levels in all subjects with and without AWP. Additional information about atopic
      diathesis, hyperhidrosis of the palms and drug intake were also collected.
      RESULTS: Thirty-one of the patients with CF (53.4%) exhibited AWP, in contrast to
      only 2 carriers (8.7%) and none in the control group. No correlation was found
      between CF genotype and AWP score severity. Twenty-three (39.7%) CF patients
      reported a history of hyperhidrosis, and in 17 of them (74%) AWP had been
      provoked. No correlation with history of atopy and lung function was noted. The
      difference between CF patients with hyperhidrosis and those without was highly
      significant (p = 0.016). Salt concentrations were significantly higher in
      patients with AWP. CONCLUSIONS: AWP is linked to CF and its diagnosis should lead
      the patients to a genetic or sweat test for CF. We found a significant
      association with hyperhidrosis and sweat electrolytes which supports the
      'hyperconcentrated sweat' pathogenetic theory of AWP.

PMID- 24434747
TI  - High-caloric and chocolate stimuli processing in healthy humans: an integration
      of functional imaging and electrophysiological findings.
AB  - There has been a great deal of interest in understanding how the human brain
      processes appetitive food cues, and knowing how such cues elicit craving
      responses is particularly relevant when current eating behavior trends within
      Westernized societies are considered. One substance that holds a special place
      with regard to food preference is chocolate, and studies that used functional
      magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have
      identified neural regions and electrical signatures that are elicited by
      chocolate cue presentations. This review will examine fMRI and ERP findings from
      studies that used high-caloric food and chocolate cues as stimuli, with a focus
      on responses observed in samples of healthy participants, as opposed to those
      with eating-related pathology. The utility of using high-caloric and chocolate
      stimuli as a means of understanding the human reward system will also be
      highlighted, as these findings may be particularly important for understanding
      processes related to pathological overeating and addiction to illicit substances.
      Finally, research from our own lab that focused on chocolate stimulus processing
      in chocolate cravers and non-cravers will be discussed, as the approach used may
      help bridge fMRI and ERP findings so that a more complete understanding of
      appetitive stimulus processing in the temporal and spatial domains may be
      established. 

PMID- 24434751
TI  - The US 2009 A(H1N1) influenza epidemic: quantifying the impact of school openings
      on the reproductive number.
AB  - BACKGROUND: There is limited information on differences in the dynamics of
      influenza transmission during time periods when schools are open compared with
      periods when they are closed. METHODS: Data on school openings, influenza
      surveillance, and absolute humidity were incorporated into a regression model to
      estimate the increase in the reproductive number for the 2009 A(H1N1) influenza
      pandemic associated with the opening of school in 10 US states. RESULTS: The
      estimate for the average increase in the reproductive number for the 2009 A(H1N1)
      influenza pandemic associated with the beginning of the school year was 19.5%
      (95% credible interval = 10%-29%). CONCLUSIONS: Whether schools are open or
      closed can have a major impact on community transmission dynamics of influenza.

PMID- 24434750
TI  - Chemical signatures and new drug targets for gametocytocidal drug development.
AB  - Control of parasite transmission is critical for the eradication of malaria.
      However, most antimalarial drugs are not active against P. falciparum
      gametocytes, responsible for the spread of malaria. Consequently, patients can
      remain infectious for weeks after the clearance of asexual parasites and clinical
      symptoms. Here we report the identification of 27 potent gametocytocidal
      compounds (IC50 < 1 MUM) from screening 5,215 known drugs and compounds. All
      these compounds were active against three strains of gametocytes with different
      drug sensitivities and geographical origins, 3D7, HB3 and Dd2. Cheminformatic
      analysis revealed chemical signatures for P. falciparum sexual and asexual stages
      indicative of druggability and suggesting potential targets. Torin 2, a top lead
      compound (IC50 = 8 nM against gametocytes in vitro), completely blocked oocyst
      formation in a mouse model of transmission. These results provide critical new
      leads and potential targets to expand the repertoire of malaria transmission
      blocking reagents. 

PMID- 24434752
TI  - Long-term mobile phone use and acoustic neuroma risk.
AB  - BACKGROUND: There is concern about potential effects of radiofrequency fields
      generated by mobile phones on cancer risk. Most previous studies have found no
      association between mobile phone use and acoustic neuroma, although information
      about long-term use is limited. METHODS: We conducted a population-based, nation
      wide, case-control study of acoustic neuroma in Sweden. Eligible cases were
      persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls
      were randomly selected from the population registry, matched on age, sex, and
      residential area. Postal questionnaires were completed by 451 cases (83%) and 710
      controls (65%). RESULTS: Ever having used mobile phones regularly (defined as
      weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18
      (95% confidence interval = 0.88 to 1.59). The association was weaker for the
      longest induction time (>=10 years) (1.11 [0.76 to 1.61]) and for regular use on
      the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of
      cumulative calling time (>=680 hours) was 1.46 (0.98 to 2.17). Restricting
      analyses to histologically confirmed cases reduced all ORs; the OR for >=680
      hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line
      phones, although with slightly higher ORs. Analyses of the complete history of
      laterality of mobile phone revealed considerable bias in laterality analyses.
      CONCLUSIONS: The findings do not support the hypothesis that long-term mobile
      phone use increases the risk of acoustic neuroma. The study suggests that phone
      use might increase the likelihood that an acoustic neuroma case is detected and
      that there could be bias in the laterality analyses performed in previous
      studies.

PMID- 24434754
TI  - Fasting therapy - old and new perspectives.

PMID- 24434753
TI  - Requirement of the expression of 3-phosphoglycerate dehydrogenase for traversing
      S phase in murine T lymphocytes following immobilized anti-CD3 activation.
AB  - Murine resting (G(0)) T lymphocytes contained no detectable mRNA of 3
      phosphoglycerate dehydrogenase (PHGDH) catalyzing the first step in the
      phosphorylated pathway of l-serine biosynthesis. Immobilized anti-CD3 activation
      of G(0) T cells expressed the PHGDH mRNA in G(1) with a maximum level in S phase.
      G(0) T cells activated with either immobilized anti-CD3 plus CsA or PBu(2), which
      failed to drive the activated T cells to enter S phase, did not express the PHGDH
      mRNA unless exogenous rIL-2 was added. Blocking of IL-2R signaling by adding anti
      IL-2 and anti-IL-2Ralpha resulted in no expression of the PHGDH mRNA during
      immobilized anti-CD3 activation of G(0) T cells. Deprivation of l-serine from
      culture medium or addition of antisense PHGDH oligonucleotide significantly
      reduced [(3)H]TdR incorporation of activated T cells. These results indicate that
      the PHGDH gene expression, dictated by IL-2R signaling, is a crucial event for
      DNA synthesis during S phase of activated T cells.

PMID- 24434755
TI  - Metabolic and psychological response to 7-day fasting in obese patients with and
      without metabolic syndrome.
AB  - BACKGROUND: Extended modified fasting is a frequently practiced tradition in
      Europe. It is claimed to improve the cardiometabolic state and physical and
      psychological well-being by an evolutionary co-developed adaptation response. We
      aimed to investigate the cardiometabolic and psychological effects of a 7-day
      fast and differences of these responses between patients with or without
      metabolic syndrome (MetS). METHODS: We investigated 30 female subjects (49.0 +/-
      8.1 years, BMI 30.4 +/- 6.7 kg/m(2)) with (n = 12) and without (n = 18) MetS. All
      subjects participated in a 7-day fast according to Buchinger with a nutritional
      energy intake of 300 kcal/day and stepwise reintroduction of solid food
      thereafter. Outcomes were assessed baseline and after fasting and included
      measures of metabolic and glucoregulatory control, adipokines as well as
      psychological well-being as assessed by Profile of Mood States (POMS) and
      Hospital Anxiety and Depression Scale (HADS). RESULTS: Mean weight decreased from
      85.4 +/- 18.8 kg to 79.7 +/- 18.2 kg accompanied by systolic/diastolic blood
      pressure (BP) reduction of -16.2 mm Hg (95% CI: -9.1; -23.3 mm Hg) and -6.0 mm Hg
      (95% CI: -1.8; -10.3 mm Hg), each p < 0.001 and p = 0.005. Fasting led to marked
      decreases of levels of LDL-cholesterol, leptin, and insulin and increases of
      levels of adiponectin, leptin receptors, and resistin. Fasting-induced mood
      enhancement was reflected by decreased anxiety, depression, fatigue, and improved
      vigor. Patients with MetS showed some greater changes in B P, LDL-cholesterol,
      triglycerides, adiponectin, leptin, and sleep quality. Fasting was well
      tolerated. CONCLUSIONS: Our results point to marked beneficial responses to 7-day
      modified fasting and a potential role in the prevention of the MetS. Randomized
      trials with longer observation periods should test the clinical effectiveness of
      fasting in metabolic diseases.

PMID- 24434756
TI  - Therapeutic fasting in patients with metabolic syndrome and impaired insulin
      resistance.
AB  - BACKGROUND: In this study, we evaluated whether a short- to mid-term fasting
      therapy (7-18 days) might improve insulin resistance according to the homeostasis
      model assessment for insulin resistance (HOMA-IR), measured during mid-term (80
      days) follow-up observation in patients with metabolic syndrome. METHODS: In this
      open label observational study in inpatients, criteria of metabolic syndrome were
      defined. Before medically controlled Buchinger fasting, a wash-out period for
      hypoglycemic agents was conducted. Further evaluation was carried out on day 80.
      RESULTS: 25 patients (13 males, 12 females, mean age 61.3 years) were included in
      this study (mean fasting duration 11.5 days). Out of 16 inpatients with type 2
      diabetes, 4 had been treated with metformin, 3 with insulin, and 1 with
      glimepiride before the intervention. After therapy, body mass index (BMI),
      fasting insulin, fasting glucose, and HOMA-IR were all significantly reduced.
      Compared to baseline, HOMA-IR decreased by 33% in all patients, by 38% in
      patients with type 2 diabetes, and by 23% in patients without diabetes. At day
      80, BMI further improved, while other parameters showed complete (insulin) or
      partial (glucose, HOMA-IR) rebound. At this time, HOMA-IR values showed an only
      insignificant improvement in 15% of all patients, in 20% of patients with type 2
      diabetes, and in 6% of patients without diabetes. There was no correlation
      between change in BMI and change in HOMA-IR (r(2) = 0.008, baseline minus day
      80). No serious side effects were observed. CONCLUSIONS: Fasting as a safe and
      acceptable procedure may cause short- and mid-term improvement of increased
      insulin resistance (HOMA-IR). Patients with type 2 diabetes benefit more than
      those without diabetes. A possible clinical significance of this effect should be
      explored in larger and controlled clinical trials.

PMID- 24434757
TI  - Anthropometric, hemodynamic, metabolic, and renal responses during 5 days of food
      and water deprivation.
AB  - BACKGROUND: Although there is considerable research in the field of fasting and
      fluid restriction, little is known about the impact of food and water deprivation
      (FWD) on body circumferences and vital parameters. METHODS: During 5 days of FWD
      in 10 healthy adults, hemodynamic, metabolic, and renal parameters, such as
      weight, 5 circumferences at neck, waist, hip, chest at axilla, chest at nipples,
      and 1 new oblique hip circumference were measured daily. For each circumference,
      new quotients of daily circumference-to-weight decrease were calculated. The set
      of employed parameters quantified and monitored dieting persons' compliance and
      efficacy of the method. RESULTS: The values of blood pressure, heart rate,
      hemoglobin oxygen saturation, glucose, K(+), Na(+), Cl(-), urea, creatinine, and
      serum osmolality proved to be stable. The mean creatinine clearance increased up
      to 167%. The mean daily weight decrease (1,390 +/- 60 g) demonstrated the
      effectiveness of FWD in weight reduction. The daily decrease of all measured
      circumferences and the values of the corresponding circumference-to-weight
      decrease quotients reflected considerable volume decrease in all measured body
      parts per day and kg of weight loss during FWD. CONCLUSION: The intervention of 5
      FWD days in 10 healthy adults was found to be safe, decreased weight and all
      measured circumferences, and improved renal function considerably.

PMID- 24434758
TI  - Fasting therapy - an expert panel update of the 2002 consensus guidelines.
AB  - Fasting for medical purpose (fasting therapy) has a long tradition in Europe and
      is established as a defined therapeutic approach in specialized fasting hospitals
      or within clinical departments for integrative medicine. In 2002, the first
      guidelines for fasting therapy were published following an expert consensus
      conference; here we present a revised update elaborated by an expert panel.
      Historical aspects and definitions, indications, methods, forms, and accompanying
      procedures of fasting as well as safety and quality criteria of fasting
      interventions are described. Fasting has shown beneficial effects in various
      chronic diseases with highest level of evidence for rheumatic diseases.
      Preliminary clinical and observational data and recently revealed mechanisms of
      fasting and caloric restriction indicate beneficial effects of fasting also in
      other chronic conditions such as metabolic diseases, pain syndromes,
      hypertension, chronic inflammatory diseases, atopic diseases, and psychosomatic
      disorders. Fasting can also be applied for preventing diseases in healthy
      subjects. In order to guarantee successful use of fasting and to ensure adherence
      of all safety and quality standards it is mandatory that all interventions during
      fasting are guided/accompanied by physicians/therapists trained and certified in
      fasting therapy.

PMID- 24434759
TI  - Fasting therapy for treating and preventing disease - current state of evidence.
AB  - Periods of deliberate fasting with restriction of solid food intake are practiced
      worldwide, mostly based on traditional, cultural or religious reasons. There is
      large empirical and observational evidence that medically supervised modified
      fasting (fasting cure, 200-500 kcal nutritional intake per day) with periods of 7
      21 days is efficacious in the treatment of rheumatic diseases, chronic pain
      syndromes, hypertension, and metabolic syndrome. The beneficial effects of
      fasting followed by vegetarian diet in rheumatoid arthritis are confirmed by
      randomized controlled trials. Further beneficial effects of fasting are supported
      by observational data and abundant evidence from experimental research which
      found caloric restriction and intermittent fasting being associated with
      deceleration or prevention of most chronic degenerative and chronic inflammatory
      diseases. Intermittent fasting may also be useful as an accompanying treatment
      during chemotherapy of cancer. A further beneficial effect of fasting relates to
      improvements in sustainable lifestyle modification and adoption of a healthy
      diet, possibly mediated by fasting-induced mood enhancement. Various identified
      mechanisms of fasting point to its potential health-promoting effects, e.g.,
      fasting-induced neuroendocrine activation and hormetic stress response, increased
      production of neurotrophic factors, reduced mitochondrial oxidative stress,
      general decrease of signals associated with aging, and promotion of autophagy.
      Fasting therapy might contribute to the prevention and treatment of chronic
      diseases and should be further evaluated in controlled clinical trials and
      observational studies.

PMID- 24434760
TI  - Too much salt and how we can get rid of it.
AB  - Humans evolved on potassium-rich diets containing only small amounts of sodium.
      Nowadays, sodium intake considerably exceeds potassium intake. However, from the
      evolutionary point of view we are not accustomed to such high salt (sodium
      chloride) ingestion. The consequences of a high dietary salt intake are primarily
      elevated blood pressure with a higher risk for cardiovascular diseases, but also
      a higher probability of developing kidney diseases and stomach cancer. High
      sodium consumption is favored by an extremely 'salty' environment, where
      palatable salty food is frequently available promoting a dietary salt overload of
      the human body. To efficiently achieve a consistent reduction in dietary salt
      intake, sodium content of food should be reduced and eating behavior modified.
      This review covers both of these aspects, including the reasons why we are not
      'programmed' to cope with high salt loads, the clinical consequences of a high
      salt consumption and the possibilities of reducing dietary salt intake and
      getting rid of the 'salty' environment.

PMID- 24434761
TI  - Eat, fast, and live longer!

PMID- 24434762
TI  - Oatmeal diet days may improve insulin resistance in patients with type 2 diabetes
      mellitus.

PMID- 24434763
TI  - [On Gehrke M, Kessler C, Zosch S: Arztekongress VegMed 2012: Medical Congress
      VegMed 2012: Vegetarian nutrition and medicine - solid evidence, but better
      implementation in general practice is necessary].

PMID- 24434764
TI  - Nutrition research in the military.
AB  - Military research performed in an operational environment involves mission
      specific considerations. The Institute of Naval Medicine was tasked in 2008 by
      the Surgeon General to investigate the nutritional status of deployed British
      military personnel, and how this might affect body composition, physical fitness
      and operational capability. This paper briefly describes the logistic and
      technical issues specific to military research that were encountered by the study
      team, how these issues were overcome and how this research has influenced
      military practice. 

PMID- 24434765
TI  - A qualitative study of the use of the four quadrant approach to assist ethical
      decision-making during deployment.
AB  - AIM: The aim of the study was to explore how useful clinicians deployed to the
      Field Hospital in Afghanistan found using the four quadrant approach (4QA) as a
      tool to aid ethical decision-making. In addition, the study aimed to determine
      whether the 4QA needed to be amended to make it more effective in assisting the
      ethical decision-making process for military health professionals on deployment.
      METHOD: A qualitative pilot study in two phases was undertaken between September
      2012 and January 2013. In Phase I, senior deployed clinicians completed a pro
      forma of the 4QA on cases that potentially raised ethical issues. Thirteen pro
      formas were submitted on four cases; the Deployed Medical Director submitted a
      log of 14 cases that had involved using the 4QA. Phase II consisted of interviews
      with five senior clinicians who had recently returned from deployment in
      Afghanistan to discuss their experiences and perceptions of using the 4QA.
      RESULTS: Phase I identified a variation in the level of detail recorded and where
      that information was placed on the quadrant. Four themes were generated from
      Phase II. These included the characteristics of ethical decisions; the processes
      used to make ethical decisions; use, usefulness and limitations of the 4QA; and
      views about training in ethics. The findings suggested that amendments to the pro
      forma may improve its utility. CONCLUSIONS: The 4QA is a useful tool within an
      operational setting but amending its diagrammatic presentation could improve its
      effectiveness. Pre-deployment training should include practising using the
      quadrant as described in Clinical Guidelines for Operations. This is particularly
      important as the participants relied heavily on experience to help them make
      ethical decisions, and this experience may not be available in future operations
      outside Afghanistan.

PMID- 24434766
TI  - Cognitive impairment in elderly renal inpatients: an under-identified phenomenon.
AB  - BACKGROUND/AIMS: Cognitive impairment is a common but under-recognised problem in
      patients with chronic kidney disease, and is likely to become more significant as
      this patient population ages. METHODS: This cross-sectional study focussed on
      inpatients aged >=65 years at a tertiary renal unit, and consisted of two parts.
      Part 1 (n = 25) considered whether cognitively impaired inpatients were being
      identified and being referred to memory services. In Part 2 (n = 105) two
      different cognitive function tests were attempted (6-CIT, MMSE). RESULTS: In Part
      1, cognitive function tests were attempted in only 4 patients at admission and 1
      patient subsequently. No patients were referred to memory services. In Part 2, 6
      CIT was abnormal (score >=8) in 61.4%, and MMSE was abnormal (score <27) in 79.5%
      (score 21-26: 28.9%, 15-20: 28.9%, 10-14: 13.3%, <10: 8.4%). There was a close
      correlation between MMSE and 6-CIT (R(2) = 0.735). Only 7.2% of those assessed
      had a documented cognitive deficit prior to admission. CONCLUSION: This is the
      first study looking at cognition in elderly inpatients with chronic kidney
      disease. There appears to be a much higher rate of cognitive impairment than
      expected and this is largely unidentified. These deficits are likely to have a
      major impact on both inpatient and outpatient management.

PMID- 24434767
TI  - Multistructural biomimetic substrates for controlled cellular differentiation.
AB  - Multidimensional scaffolds are considered to be ideal candidates for regenerative
      medicine and tissue engineering based on their potential to provide an excellent
      microenvironment and direct the fate of the cultured cells. More recently, the
      use of stem cells in medicine has opened a new technological opportunity for
      controlled tissue formation. However, the mechanism through which the substrate
      directs the differentiation of stem cells is still rather unclear. Data
      concerning its specific surface chemistry, topology, and its signaling ability
      need to be further understood and analyzed. In our study, atomic force microscopy
      was used to study the stiffness, roughness, and topology of the collagen (Coll)
      and metallized collagen (MC) substrates, proposed as an excellent substrate for
      regenerative medicine. The importance of signaling molecules was studied by
      constructing a new hybrid signaling substrate that contains both collagen and
      laminin extracellular matrix (ECM) proteins. The cellular response-such as
      attachment capability, proliferation and cardiac and neuronal phenotype
      expression on the metallized and non-metallized hybrid substrates (collagen +
      laminin)-was studied using MTT viability assay and immunohistochemistry studies.
      Our findings indicate that such hybrid materials could play an important role in
      the regeneration of complex tissues. 

PMID- 24434768
TI  - Muscle tension induced after learning enhances long-term narrative and visual
      memory in healthy older adults.
AB  - Arousing events are better remembered than mundane events. Indeed, manipulation
      of arousal, such as by muscle tension, can influence memory even when it occurs
      shortly after learning. Indeed, our founding study showed this approach can raise
      delayed memory performance in older adults to a level comparable to that of
      unaided young adults. Yet, systematic studies, especially those investigating
      different modalities or types of memory, have not been done. This study
      investigated the effects of a brief bout of isometric exercise via handgrip on
      narrative and visuospatial episodic memory in healthy elders. Forty-seven
      participants completed the Logical Memory subtest of the Wechsler Memory Scales
      III (LM) and the Benton Visual Retention Test (BVRT), followed alternately by no
      treatment and by moderately squeezing a sand-filled latex ball for 1-min
      (counterbalanced order and test forms). Isometric exercise significantly
      increased both positive and negative affect ratings. Retention was tested 2 weeks
      later. Delayed recall and recognition of LM was enhanced by arousal relative to
      control, as was recognition of the BVRT. The results extend past findings that
      muscle tension induced after learning modulates memory consolidation, extending
      findings in elders to suggest that a simple form of isometric exercise can have
      practical effects, such as aiding memory for stories and images.

PMID- 24434769
TI  - Modulation of oxidative stress and Ca(2+) mobilization through TRPM2 channels in
      rat dorsal root ganglion neuron by Hypericum perforatum.
AB  - A main component of St. John's Wort (Hypericum perforatum, HP) is hyperforin
      which has antioxidant properties in dorsal root ganglion (DRG) neurons, due to
      its ability to modulate NADPH oxidase and protein kinase C. Recent reports
      indicate that oxidative stress through NADPH oxidase activates TRPM2 channels. HP
      may be a useful treatment for Ca(2+) entry and oxidative stress through
      modulation of TRPM2 channels in the DRG. We aimed to investigate the protective
      role of HP on Ca(2+) entry and oxidative stress through TRPM2 channels in DRG
      neurons of rats. The native rat DRG neurons were used in whole-cell patch-clamp,
      Fura-2 and antioxidant experiments. Appropriate, nontoxic concentrations and
      incubation times for HP were determined in the DRG neurons by assessing cell
      viability. The H2O2-induced TRPM2 currents were inhibited by 2-aminoethyl
      diphenylborinate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA). TRPM2
      current densities and cytosolic free Ca(2+) concentration in the neurons were
      also reduced by HP (2 and 24h). In Fura-2 experiments, cytosolic Ca(2+)
      mobilization was reduced by voltage-gated calcium channel blockers
      (verapamil+diltiazem, V+D) and HP. Glutathione peroxidase activity and GSH values
      in the DRG were high in HP, 2-APB and V+D groups although lipid peroxidation
      level was low in the groups. In conclusion, we observed a protective role for HP
      on Ca(2+) entry through a TRPM2 channel in the DRG neurons. Since over-production
      of oxidative stress and Ca(2+) entry are implicated in the pathophysiology of
      neuropathic pain and neuronal inflammation, our findings may be relevant to the
      etiology and treatment of neuropathology in DRG neurons. 

PMID- 24434770
TI  - Cannabinoid type-1 receptors in the paraventricular nucleus of the hypothalamus
      inhibit stimulated food intake.
AB  - Cannabinoid receptor type 1 (CB1)-dependent signaling in the brain is known to
      modulate food intake. Recent evidence has actually shown that CB1 can both
      inhibit and stimulate food intake in fasting/refeeding conditions, depending on
      the specific neuronal circuits involved. However, the exact brain sites where
      this bimodal control is exerted and the underlying neurobiological mechanisms are
      not fully understood yet. Using pharmacological and electrophysiological
      approaches, we show that local CB1 blockade in the paraventricular nucleus of the
      hypothalamus (PVN) increases fasting-induced hyperphagia in rats. Furthermore,
      local CB1 blockade in the PVN also increases the orexigenic effect of the gut
      hormone ghrelin in animals fed ad libitum. At the electrophysiological level, CB1
      blockade in slices containing the PVN potentiates the decrease of the activity of
      PVN neurons induced by long-term application of ghrelin. Hence, the PVN is (one
      of) the site(s) where signals associated with the body's energy status determine
      the direction of the effects of endocannabinoid signaling on food intake. 

PMID- 24434771
TI  - Etazolate abrogates the lipopolysaccharide (LPS)-induced downregulation of the
      cAMP/pCREB/BDNF signaling, neuroinflammatory response and depressive-like
      behavior in mice.
AB  - Increasing evidence has indicated that immune challenge by bacterial
      lipopolysaccharide (LPS) induces depressive-like behavior, neuroinflammatory
      response and upregulates phosphodiesterase-4 (PDE4), an enzyme that specifically
      hydrolyzes cyclic adenosine monophosphate (cAMP). However, whether the potential
      PDE4 inhibitor etazolate prevents the LPS-induced depressive-like behavior
      remains unclear. Here using a model of depression induced by the repeated
      administration of LPS during 16days, and then investigated the influence of LPS
      on the expression of PDE4, interleukin-1beta (IL-1beta) and antidepressant action
      of etazolate in mice through forced swimming, novelty suppressed feeding, sucrose
      preference and open-field tests. Our results showed that etazolate pretreatment
      facilitated the recovery from weight loss and prevented the depressive-like
      behavior induced by repeated LPS administration. Moreover, the antidepressant
      action of etazolate was paralleled by significantly reducing the expression
      levels of PDE4A, PDE4B, PDE4D and IL-1beta and up-regulating the
      cAMP/phosphorylated cAMP response-element binding protein (pCREB)/brain-derived
      neurotrophic factor (BDNF) signaling in the hippocampus and prefrontal cortex of
      mice. These results indicate that the effects of etazolate on the depressive-like
      behavior induced by repeated LPS treatment may partially depend on the inhibition
      of PDE4 subtypes, the activation of the cAMP/pCREB/BDNF signaling and the anti
      inflammatory responses in the hippocampus and prefrontal cortex. 

PMID- 24434772
TI  - GABAergic synaptic transmission onto striatal cholinergic interneurons in
      dopamine D2 receptor knock-out mice.
AB  - Whole-cell or cell-attached analysis was carried out in dopamine (DA) D2 receptor
      (D2R) knock-out (KO) mice to elucidate the function of this receptor in the
      regulation of GABAergic synaptic transmission onto striatal cholinergic
      interneurons as well as their spontaneous firing. In slice preparation obtained
      from wild-type mice, evoked GABAergic inhibitory postsynaptic currents (IPSCs)
      showed frequency-dependent suppression, and this suppression significantly
      decreased in the presence of a D2-like receptor antagonist or in D2R KO mice.
      Contribution of N-type calcium channel was also significantly reduced in the
      striatal cholinergic interneurons of the D2R KO mice compared with that in the
      wild-type mice. Spontaneous firing of striatal cholinergic interneurons was
      inhibited by 5- or 10-Hz stimulation, and the suppression was decreased in the
      presence of a D2-like receptor antagonist or in D2R KO mice. These findings
      substantiate the physiological role of D2R in the regulation of GABAergic
      synaptic transmission onto striatal cholinergic interneurons as well as their
      excitability, confirming the tight coupling between D2R and N-type calcium
      channels in the regulation of GABA release. 

PMID- 24434774
TI  - Modulation of spinal excitability by a sub-threshold stimulation of M1 area
      during muscle lengthening.
AB  - It is well known that the H-reflex amplitude decreases during passive muscle
      lengthening in comparison with passive shortening. However, this decrease in
      spinal synaptic efficacy observed during passive lengthening seems to be lesser
      during eccentric voluntary contraction. The aim of the present study was to
      examine whether spinal excitability during lengthening condition could be
      modulated by magnetic brain stimulation. H reflexes of the triceps surae muscles
      were elicited on 10 young healthy subjects, and conditioned by a sub-threshold
      transcranial magnetic stimulation (TMS). The conditioning stimulation was applied
      over the M1 area of triceps surae muscles at an intensity below motor threshold
      with a conditioning-test interval of 5ms. Conditioned and non-conditioned H
      reflexes were elicited at rest, during passive lengthening and shortening, and
      during submaximal contractions (concentric, eccentric and isometric). During
      passive and active lengthening, H reflexes conditioned by a sub-threshold TMS
      pulse increased on average by 50% compared with non-conditioned responses. No
      significant effect was found during isometric and concentric conditions.
      Activation of the corticospinal pathway would partially cancel inhibitions caused
      by muscle stretch, and according to the time-delayed effect, this result
      suggested the existence of a specific polysynaptic pathway. In additional
      experiments, H responses were conditioned by cervico-medullary stimulations,
      showing that the modulation described by the previous results involves
      subcortical mechanisms. This study provides further evidences that the modulation
      of the final cortico-spinal command reaching the muscle depends on a central
      mechanism that controls peripheral input, such as Ia afference discharge during
      lengthening. 

PMID- 24434775
TI  - Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for
      patients with prostate cancer.
AB  - We designed and constructed an in vivo dosimetry system using plastic
      scintillation detectors (PSDs) to monitor dose to the rectal wall in patients
      undergoing intensity-modulated radiation therapy for prostate cancer. Five
      patients were enrolled in an Institutional Review Board-approved protocol for
      twice weekly in vivo dose monitoring with our system, resulting in a total of 142
      in vivo dose measurements. PSDs were attached to the surface of endorectal
      balloons used for prostate immobilization to place the PSDs in contact with the
      rectal wall. Absorbed dose was measured in real time and the total measured dose
      was compared with the dose calculated by the treatment planning system on the
      daily computed tomographic image dataset. The mean difference between measured
      and calculated doses for the entire patient population was -0.4% (standard
      deviation 2.8%). The mean difference between daily measured and calculated doses
      for each patient ranged from -3.3% to 3.3% (standard deviation ranged from 5.6%
      to 7.1% for four patients and was 14.0% for the last, for whom optimal
      positioning of the detector was difficult owing to the patient's large size).
      Patients tolerated the detectors well and the treatment workflow was not
      compromised. Overall, PSDs performed well as in vivo dosimeters, providing
      excellent accuracy, real-time measurement and reusability. 

PMID- 24434773
TI  - Separating analgesia from reward within the ventral tegmental area.
AB  - Activation of the dopaminergic mesolimbic reward circuit that originates in the
      ventral tegmental area (VTA) is postulated to preferentially suppress emotional
      responses to noxious stimuli, and presumably contributes to the addictive
      liability of strong analgesics. VTA dopamine neurons are activated via
      cholinergic afferents and microinjection of carbachol (cholinergic agonist) into
      VTA is rewarding. Here, we evaluated regional differences within VTA in the
      capacity of carbachol to suppress rats' affective response to pain (vocalization
      afterdischarges, VADs) and to support conditioned place preference (CPP)
      learning. As carbachol is a non-specific agonist, muscarinic and nicotinic
      receptor involvement was assessed by administering atropine (muscarinic
      antagonist) and mecamylamine (nicotinic antagonist) into VTA prior to carbachol
      treatment. Unilateral injections of carbachol (4MUg) into anterior VTA (aVTA) and
      posterior VTA (pVTA) suppressed VADs and supported CPP; whereas, injections into
      midVTA failed to effect either VADs or CPP. These findings corroborate the
      hypothesis that the neural substrates underlying affective analgesia and reward
      overlap. However, the extent of the overlap was only partial. Whereas both
      nicotinic and muscarinic receptors contributed to carbachol-induced affective
      analgesia in aVTA, only muscarinic receptors mediated the analgesic action of
      carbachol in pVTA. The rewarding effects of carbachol are mediated by the
      activation of both nicotinic and muscarinic receptors in both aVTA and pVTA. The
      results indicate that analgesia and reward are mediated by separate cholinergic
      mechanisms within pVTA. Nicotinic receptor antagonism within pVTA failed to
      attenuate carbachol-induced analgesia, but prevented carbachol-induced reward. As
      addictive liability of analgesics stem from their rewarding properties, the
      present findings suggest that these processes can be neuropharmacologically
      separated within pVTA. 

PMID- 24434776
TI  - Folliculin deficient renal cancer cells show higher radiosensitivity through
      autophagic cell death.
AB  - PURPOSE: Mutations in the FLCN gene are responsible for fibrofolliculoma,
      pulmonary and renal cysts, and renal cell carcinoma in patients with Birt-Hogg
      Dube syndrome. To explore therapeutic approaches to renal cell carcinoma in
      patients with Birt-Hogg-Dube syndrome we investigated the anticancer effects of
      irradiation on folliculin deficient renal cancer cells. MATERIALS AND METHODS:
      Folliculin deficient (UOK257 and ACHN-5968) and folliculin expressing (UOK257-2
      and ACHN-sc) cell lines were used in this study. Clonogenic assays were used to
      determine the radiosensitivity of folliculin deficient and expressing renal cell
      carcinoma cells. Apoptosis was detected in these cells by DAPI and TUNEL assays
      after irradiation. Monodansylcadaverine analysis, GFP-LC3 assay and Western blot
      were performed to monitor the autophagic process. RESULTS: Folliculin deficient
      cells were more sensitive to irradiation than their folliculin expressing
      counterparts. The enhanced effects of irradiation on folliculin deficient cells
      were mediated by increased autophagy but not by apoptosis. An increased Beclin 1
      protein level and an activated mitogen-activated protein kinase pathway were
      identified as the key regulators of increased autophagy in these folliculin
      deficient cells. Inhibiting autophagy with 3-methyladenine or beclin 1 siRNA
      obviously increased radioresistance in folliculin deficient cells. Moreover,
      irradiation combined with autophagic inducer rapamycin significantly increased
      autophagy and radiosensitivity in folliculin deficient renal cell carcinoma
      cells. CONCLUSIONS: Findings suggest that folliculin deficient renal cell
      carcinoma cells are highly sensitive to irradiation due to increased autophagic
      cell death, unlike other types of renal cell carcinoma. Irradiation plus
      autophagy inducers, eg rapamycin, might be a potentially more effective
      therapeutic approach to folliculin deficient renal cell carcinoma.

PMID- 24434777
TI  - Neonatal morbidity occurs despite pulmonary maturity prior to 39 weeks gestation.
AB  - OBJECTIVE: To compare outcomes among late-preterm or early-term neonates
      according to fetal lung maturity (FLM) status. STUDY DESIGN: We conducted a
      retrospective cohort study of 234 eligible singletons delivered after FLM testing
      before 39 weeks gestation at our center over a 2-year time period. A primary
      composite neonatal outcome included death and major morbidities. RESULT: The
      overall rate of primary composite morbidity was 25/46 (52.2%) and 61/188 (32.4%)
      in the immature/transitional and mature groups, respectively. After adjustment
      for confounders including gestational age, the composite outcome was not
      significantly different; adjusted odds ratio (aOR)=1.4 (confidence interval
      (CI)=0.7-3.0). The rate of respiratory distress syndrome was significantly higher
      in the immature/transitional group; odds ratio=3.4 (CI=1.1-10.3) as expected.
      CONCLUSION: FLM status did not correlate with the spectrum of neonatal
      morbidities in late-preterm and early-term births. Neonatal complications
      remained common in both groups.

PMID- 24434778
TI  - Risk of necrotizing enterocolitis in very-low-birth-weight infants with isolated
      atrial and ventricular septal defects.
AB  - OBJECTIVE: Necrotizing enterocolitis (NEC) is associated with a significant
      morbidity and mortality in premature infants. We sought to identify the frequency
      of NEC in very-low-birth-weight infants with isolated ventricular septal defects
      (VSDs) or atrial septal defects (ASDs) using a large multicenter database. STUDY
      DESIGN: We identified a cohort of infants with birth weight <1500 g cared for in
      312 neonatal intensive care units (NICUs) managed by the Pediatrix Medical Group
      between 1997 and 2010. We examined the association between the presence of an ASD
      or a VSD with development of NEC using logistic regression to control for small
      for-gestational age status, antenatal steroid use, antenatal antibiotic use,
      gestational age, sex, race, Apgar score at 5 min and method of delivery. RESULT:
      Of the 98 523 infants who met inclusion criteria, 1904 (1.9%) had an ASD, 1943
      (2.0%) had a VSD and 146 (0.1%) had both. The incidence of NEC was 6.2% in
      infants without septal defects, 9.3% in those with an ASD, 7.8% in those with a
      VSD, and 10.3% in infants with both an ASD and a VSD. Compared with infants
      without septal defects, the adjusted odds ratios for developing NEC for each
      group-ASD alone, VSD alone and ASD with VSD-were 1.26 (95% confidence interval
      1.07 to 1.49), 1.27 (1.07 to 1.51) and 1.79 (1.03 to 3.12), respectively.
      CONCLUSION: The presence of an ASD or a VSD was associated with NEC in this
      cohort of premature infants.

PMID- 24434779
TI  - Placental pathology, first-trimester biomarkers and adverse pregnancy outcomes.
AB  - OBJECTIVE: We investigated the relationship between placental pathological
      findings in pregnancies with adverse pregnancy outcomes and first-trimester serum
      analytes and uterine artery Doppler results. STUDY DESIGN: This is a secondary
      analysis of a prospective study of first-trimester screening for adverse
      pregnancy outcomes, including preterm birth (PTB (delivery<37 weeks)), pre
      eclampsia (PE), gestational hypertension, and small for gestational age (SGA)
      infants (birth weight <10th percentile). We compared the mean levels of serum
      analytes (pregnancy-associated plasma protein A (PAPP-A), placental protein 13
      (PP13), a-disintegrin and metalloproteinase 12 (ADAM12), placental growth factor
      (PLGF)) and uterine artery Doppler pulsatility index (UADPI) obtained between 11
      and 14 weeks gestation in cases with adverse outcomes and abnormal placental
      histology to a control group without adverse outcome or abnormal placental
      pathology. Placental findings were classified as: lesions of maternal under
      perfusion, lesions causing reduced placental reserve, infections/inflammatory
      lesions, and fetal vascular lesions. RESULT: Among 193 cases, lesions of maternal
      under perfusion were seen in 50 cases (25.9%), lesions causing reduced placental
      reserve in 63 cases (32.8%), infection/inflammation in 65 cases (34.2%) and fetal
      vascular lesions in 23 cases (11.9%). There were 123 pregnancies with no adverse
      pregnancy outcome or placental lesion used as controls. Pregnancies with PE had a
      significant association with lesions of maternal under perfusion (P=0.005) and
      placental infection/inflammation (P=0.003). Significant differences were seen in
      mean levels of PAPP-A, ADAM12 and PLGF in cases with PE, PTB and SGA with
      specific placental histological findings when compared with controls. UADPI was
      not significantly different between the cases with adverse pregnancy outcomes and
      abnormal histology. CONCLUSION: Our findings provide evidence linking placental
      pathology with suboptimal secretion of analytes in the first trimester in
      pregnancies with adverse outcomes, especially PE.

PMID- 24434780
TI  - JNK1 stress signaling is hyper-activated in high breast density and the tumor
      stroma: connecting fibrosis, inflammation, and stemness for cancer prevention.
AB  - Mammography is an important screening modality for the early detection of DCIS
      and breast cancer lesions. More specifically, high mammographic density is
      associated with an increased risk of breast cancer. However, the biological
      processes underlying this phenomenon remain largely unknown. Here, we re
      interrogated genome-wide transcriptional profiling data obtained from low-density
      (LD) mammary fibroblasts (n = 6 patients) and high-density (HD) mammary
      fibroblasts (n = 7 patients) derived from a series of 13 female patients. We used
      these raw data to generate a "breast density" gene signature consisting of>1250
      transcripts that were significantly increased in HD fibroblasts, relative to LD
      fibroblasts. We then focused on the genes that were increased by >= 1.5-fold
      (P<0.05) and performed gene set enrichment analysis (GSEA), using the molecular
      signatures database (MSigDB). Our results indicate that HD fibroblasts show the
      upregulation and/or hyper-activation of several key cellular processes, including
      the stress response, inflammation, stemness, and signal transduction. The
      transcriptional profiles of HD fibroblasts also showed striking similarities to
      human tumors, including head and neck, liver, thyroid, lung, and breast cancers.
      This may reflect functional similarities between cancer-associated fibroblasts
      (CAFs) and HD fibroblasts. This is consistent with the idea that the presence of
      HD fibroblasts may be a hallmark of a pre-cancerous phenotype. In these
      biological processes, GSEA predicts that several key signaling pathways may be
      involved, including JNK1, iNOS, Rho GTPase(s), FGF-R, EGF-R, and PDGF-R-mediated
      signal transduction, thereby creating a pro-inflammatory, pro-proliferative,
      cytokine, and chemokine-rich microenvironment. HD fibroblasts also showed
      significant overlap with gene profiles derived from smooth muscle cells under
      stress (JNK1) and activated/infected macrophages (iNOS). Thus, HD fibroblasts may
      behave like activated myofibroblasts and macrophages, to create and maintain a
      fibrotic and inflammatory microenvironment. Finally, comparisons between the HD
      fibroblast gene signature and breast cancer tumor stroma revealed that JNK1
      stress signaling is the single most significant biological process that is shared
      between these 2 data sets (with P values between 5.40E-09 and 1.02E-14), and is
      specifically associated with tumor recurrence. These results implicate "stromal
      JNK1 signaling" in the pathogenesis of human breast cancers and the transition to
      malignancy. Augmented TGF-beta signaling also emerged as a common feature linking
      high breast density with tumor stroma and breast cancer recurrence (P = 5.23E
      05). Similarities between the HD fibroblast gene signature, wound healing, and
      the cancer-associated fibroblast phenotype were also noted. Thus, this unbiased
      informatics analysis of high breast density provides a novel framework for
      additional experimental exploration and new hypothesis-driven breast cancer
      research, with a focus on cancer prevention and personalized medicine. 

PMID- 24434781
TI  - Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell
      transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or
      mantle cell lymphoma.
AB  - A phase I/II trial was designed to evaluate the safety and efficacy of adding
      bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and
      autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had
      relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell
      lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete
      remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before
      ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients
      were accrued to each. Any nonhematological ASCT-related toxicity >2 on the
      Bearman scale occurring between day -11 and engraftment defined the maximum
      tolerated dose (MTD). After the MTD has been reached, another 20 patients were
      enrolled at this dose to determine a preliminary overall response rate (ORR).
      Patients who were in CR or PR at day +100 were considered responders. The study
      enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to
      73) years, with 33 males and 9 females. The most common diagnoses were MCL (23
      patients) and follicular lymphoma (7 patients). The median number of prior
      therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to
      6.98) years. Thirteen patients were treated in phase I and 29 patients were
      treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it
      was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity
      and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all
      38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive
      disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1
      year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79%
      to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National
      Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%),
      peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and
      1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls
      treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and
      57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1
      and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM
      group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P =
      .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable
      and we did not observe any treatment-related mortalities; however, we did observe
      an excess of autonomic dysfunction and ileus, which is concerning for overlapping
      toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared
      to BEAM would require a randomized trial.

PMID- 24434782
TI  - Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high
      affinity IL-2 receptor on human cytokine-induced memory-like natural killer
      cells.
AB  - Natural killer (NK) cells are effector lymphocytes that are under clinical
      investigation for the adoptive immunotherapy of hematologic malignancies,
      especially acute myeloid leukemia. Recent work in mice has identified innate
      memory-like properties of NK cells. Human NK cells also exhibit memory-like
      properties, and cytokine-induced memory-like (CIML) NK cells are generated via
      brief preactivation with IL-12, IL-15, and IL-18, which later exhibit enhanced
      functionality upon restimulation. However, the optimal cytokine receptors and
      signals for maintenance of enhanced function and homeostasis after preactivation
      remain unclear. Here, we show that IL-12, IL-15, and IL-18 preactivation induces
      a rapid and prolonged expression of CD25, resulting in a functional high-affinity
      IL-2 receptor (IL-2Ralphabetagamma) that confers responsiveness to picomolar
      concentrations of IL-2. The expression of CD25 correlated with STAT5
      phosphorylation in response to picomolar concentrations of IL-2, indicating the
      presence of a signal-competent IL-2Ralphabetagamma. Furthermore, picomolar
      concentrations of IL-2 acted synergistically with IL-12 to costimulate IFN-gamma
      production by preactivated NK cells, an effect that was CD25 dependent. Picomolar
      concentrations of IL-2 also enhanced NK cell proliferation and cytotoxicity via
      the IL-2Ralphabetagamma. Further, after adoptive transfer into immunodeficient
      NOD-SCID-gammac(-/-) mice, human cytokine-preactivated NK cells expand
      preferentially in response to exogenous IL-2. Collectively, these data
      demonstrate that human CIML NK cells respond to IL-2 via IL-2Ralphabetagamma with
      enhanced survival and functionality, and they provide additional rationale for
      immunotherapeutic strategies that include brief cytokine preactivation before
      adoptive NK cell transfer, followed by low-dose IL-2 therapy. 

PMID- 24434784
TI  - Sexual transmission of giardiasis: a neglected route of spread?
AB  - Sexually transmitted infections (STIs) are often discussed in the context of
      syphilis, gonorrhea, herpes, chlamydiasis and AIDS. However, since the past 30
      years of the last century, epidemiology and natural history studies have led to
      improved understanding of giardiasis as a STI, as a result of oral-anal sexual
      contact. Studies suggest that Giardia is an increasingly recognized infection
      that may be underdiagnosed under the STI context. Health care providers should
      maintain a high index of suspicion for Giardia, obtain suitable diagnostic tests
      to identify and screen those at high risk for this infection, institute
      appropriate therapy, counsel patients regarding treatment compliance, follow-up,
      encourage partner notification and teach strategies for preventing the
      transmission of this disease, including the discussion of the risk of enteric
      infections after oral-anal sexual contact. We summarize some data concerning the
      research and clinical literature on Giardia infection as a STI and identify the
      specific recommendations for control of giardiasis as STI that available evidence
      indicates can reduce its transmission. 

PMID- 24434783
TI  - Adjustment in parents of children undergoing stem cell transplantation.
AB  - Pediatric stem cell transplantation (SCT) is a demanding procedure for children
      and parents. Interventions to promote positive adjustment of parents in this
      setting are needed. A total of 171 patient-parent dyads from 4 sites received 1
      of 3 interventions to reduce SCT-related distress: a child intervention with
      massage and humor therapy, an identical child intervention plus a parent
      intervention with massage and relaxation/imagery, or standard care. Parents
      completed weekly self-report measures of distress and positive affect during the
      acute phase of treatment (weeks -1 through +6); and measures of depression,
      posttraumatic stress (PTSD), and benefit finding at baseline and week +24. No
      significant differences across treatment arms were observed on repeated measures
      of parental distress. There was a marginally significant effect of the child
      intervention on parental positive affect. Over time, parental distress decreased
      significantly and positive affect increased significantly in all groups.
      Similarly, there were no significant intervention effects on the global
      adjustment outcomes of depression, PTSD, and benefit finding. However, reports of
      depression and PTSD decreased significantly and reports of benefit finding
      increased significantly from baseline to week +24 for all groups. Across all
      study arms, parent adjustment improved over time, suggesting that parents
      demonstrate a transient period of moderately elevated distress at the time of
      their child's admission for transplantation, followed by rapid improved to
      normative levels of adjustment. Similar to results previously reported for their
      children, these parents appear resilient to the challenges of transplantation.

PMID- 24434785
TI  - Effect of estrogen receptor alpha binding on functional DNA methylation in breast
      cancer.
AB  - Epigenetic modifications introduce an additional layer of regulation that
      drastically expands the instructional capability of the human genome. The
      regulatory consequences of DNA methylation is context dependent; it can induce,
      enhance, and suppress gene expression, or have no effect on gene regulation.
      Therefore, it is essential to account for the genomic location of its occurrence
      and the protein factors it associates with to improve our understanding of its
      function and effects. Here, we use ENCODE ChIP-seq and DNase I hypersensitivity
      data, along with large-scale breast cancer genomic data from The Cancer Genome
      Atlas (TCGA) to computationally dissect the intricacies of DNA methylation in
      regulation of cancer transcriptomes. In particular, we identified a relationship
      between estrogen receptor alpha (ERalpha) activity and DNA methylation patterning
      in breast cancer. We found compelling evidence that methylation status of DNA
      sequences at ERalpha binding sites is tightly coupled with ERalpha activity.
      Furthermore, we predicted several transcription factors including FOXA1, GATA1,
      and SUZ12 to be associated with breast cancer by examining the methylation status
      of their binding sites in breast cancer. Lastly, we determine that methylated
      CpGs highly correlated with gene expression are enriched in regions 1kb or more
      downstream of TSSs, suggesting more significant regulatory roles for CpGs distal
      to gene TSSs. Our study provides novel insights into the role of ERalpha in
      breast cancers. 

PMID- 24434786
TI  - WHO Collaborating Centre for Acquired Immunodeficiency Syndrome for the Eastern
      Mediterranean Regional Office, Faculty of Medicine, Kuwait University, Kuwait.
AB  - In the early 1980s, the World Health Organization (WHO) designated the Virology
      Unit of the Faculty of Medicine, Health Sciences Centre, Kuwait University,
      Kuwait, a collaborating centre for AIDS for the Eastern Mediterranean Regional
      Office (EMRO), recognizing it to be in compliance with WHO guidelines. In this
      centre, research integral to the efforts of WHO to combat AIDS is conducted. In
      addition to annual workshops and symposia, the centre is constantly updating and
      renewing its facilities and capabilities in keeping with current and latest
      advances in virology. As an example of the activities of the centre, the HIV-1
      RNA viral load in plasma samples of HIV-1 patients is determined by real-time PCR
      using the AmpliPrep TaqMan HIV-1 test v2.0. HIV-1 drug resistance is determined
      by sequencing the reverse transcriptase and protease regions on the HIV-1 pol
      gene, using the TRUGENE HIV-1 Genotyping Assay on the OpenGene(r) DNA Sequencing
      System. HIV-1 subtypes are determined by sequencing the reverse transcriptase and
      protease regions on the HIV-1 pol gene using the genotyping assays described
      above. A fundamental program of Kuwait's WHO AIDS collaboration centre is the
      national project on the surveillance of drug resistance in human deficiency virus
      in Kuwait, which illustrates how the centre and its activities in Kuwait can
      serve the EMRO region of WHO.

PMID- 24434787
TI  - Intrinsically higher fatigue cracking resistance of the penetrable and movable
      incoherent twin boundary.
AB  - Incoherent twin boundaries (ITBs) are widespread and play a crucial role in
      unidirectional deformation behavior of materials, however, the intrinsic role of
      individual ITB under cyclic loading remains elusive. Here we show the fatigue
      cracking behavior of Cu bicrystal with an ITB as its sole interface for the first
      time. The slip bands (SBs) could transfer through the ITB; meanwhile, the ITB
      could migrate with the motion of partial dislocations. Both the penetrability and
      mobility contribute to the higher fatigue cracking resistance of the ITB and
      hence the fatigue crack nucleates along the SBs preferentially. These new
      findings not only shed light on the fatigue cracking mechanisms of a penetrable
      boundary with direct evidence but also could provide important implications for
      future interfacial optimization of metallic materials. 

PMID- 24434789
TI  - X-ray absorption spectroscopy and resonant inelastic scattering study of the
      first lithiation cycle of the Li-ion battery cathode Li(2-x)MnSiO4.
AB  - We employ soft X-ray absorption spectroscopy and resonant inelastic X-ray
      scattering spectroscopy to study the redox behavior in the first
      lithiation/delithiation cycle of Li(2-x)MnSiO4 (4.0-4.6 V). For extraction of
      lithium ions up to an end potential of 4.1 V, we do not detect any change in the
      oxidation state for the expected redox-active Mn atom, instead the electronic
      structure of the Si-O network is affected. Above 4.1 V, there is an abrupt change
      in the oxidation state of the Mn-ions, from 2+ to 4+, which is accompanied by a
      complete loss of long range order in the material, as detected by X-ray
      diffraction. Further lithium extraction leads to progressive loss of
      crystallinity of Li(2-x)MnSiO4, rather than formation of a new structure,
      explaining the measured first-cycle capacity loss of this material. Our results
      suggest that future improvement of the crystalline stability of the material,
      particularly with respect to the SiO4 network, is required to harness the full
      charge capacity of Li(2-x)MnSiO4.

PMID- 24434788
TI  - The emerging potential of autophagy-based therapies in the treatment of cystic
      fibrosis lung infections.
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR), a channel that normally transports anions across epithelial
      cell membranes. The most common manifestation of CF is buildup of mucus in the
      airways and bacterial colonization of the lower respiratory tract, accompanied by
      chronic inflammation. Antibiotics are used to control CF-associated opportunistic
      infections, but lengthy antibiotic treatment risks the emergence of multiple-drug
      resistant (MDR) strains. New antimicrobial strategies are needed to prevent and
      treat infections in these high-risk individuals. Autophagy contributes to the
      control of a variety of microbial infections. For this reason, the recent
      discovery of functional impairment of autophagy in CF provides a new basis for
      understanding susceptibility to severe infections. Here, we review the role of
      autophagy in host defense against CF-associated bacterial and fungal pathogens,
      and survey pharmacologic approaches to restore normal autophagy function in these
      individuals. Autophagy restoration therapy may improve pathogen clearance and
      mitigate lung inflammation in CF airways. 

PMID- 24434790
TI  - Proteomic analysis of whole glomeruli in patients with IgA nephropathy using
      microsieving.
AB  - BACKGROUND: To promote understanding of immunoglobulin A nephropathy (IgAN)
      pathophysiology, we tried to elucidate glomerular protein profiles in IgAN, using
      microsieving that we established recently to isolate glomeruli from renal biopsy
      samples and proteomic approaches. METHODS: Glomeruli were isolated from renal
      biopsy samples of patients with IgAN (n = 5) and with minimal change nephrotic
      syndrome (MCNS; n = 5) using microsieving. Proteins extracted from the isolated
      glomeruli were separated by 2-dimensional differential gel electrophoresis (2D
      DIGE). Proteins with different amounts between the two groups were identified by
      mass spectrometry. One of the identified proteins, alpha-actinin-4 (ACTN4), was
      further analyzed by Western blotting, RT-polymerase chain reaction (PCR), and
      immunohistochemistry. RESULTS: By 2D-DIGE, 72 out of the detected 1,170 protein
      spots showed significantly different intensity between the two groups (p < 0.05).
      Thirty-four out of the 72 protein spots showed more than 1.5-fold or less than
      1/1.5-fold intensity, out of which 16 protein spots were successfully identified.
      No microbial protein was identified. ACTN4 molecules with a low molecular weight
      of approximately 77 kDa were found to increase in the IgAN group. Lack of an N
      terminal part of ACTN4 was demonstrated by Western blotting. No defect of mRNA
      for ACTN4 was evidenced by RT-PCR. Predominant existence of ACTN4 in capillary
      walls of glomeruli of IgAN patients was demonstrated by immunohistochemistry in
      glomerular sections of patients with IgAN. CONCLUSION: Use of microsieving
      enabled us to biochemically analyze glomerular proteins in renal biopsy samples
      from patients with glomerular diseases. With this method, we demonstrated skewed
      glomerular protein profiles in IgAN.

PMID- 24434792
TI  - Dose in x-ray computed tomography.
AB  - Radiation dose in x-ray computed tomography (CT) has become a topic of high
      interest due to the increasing numbers of CT examinations performed worldwide.
      This review aims to present an overview of current concepts for both scanner
      output metrics and for patient dosimetry and will comment on their strengths and
      weaknesses. Controversial issues such as the appropriateness of the CT dose index
      (CTDI) are discussed in detail. A review of approaches to patient dose assessment
      presently in practice, of the dose levels encountered and options for further
      dose optimization are also given and discussed. Patient dose assessment remains a
      topic for further improvement and for international consensus. All approaches
      presently in use are based on Monte Carlo (MC) simulations. Estimates for
      effective dose are established, but they are crude and not patient-specific;
      organ dose estimates are rarely available. Patient- and organ-specific dose
      estimates can be provided with adequate accuracy and independent of CTDI phantom
      measurements by fast MC simulations. Such information, in particular on 3D dose
      distributions, is important and helpful in optimization efforts. Dose
      optimization has been performed very successfully in recent years and even
      resulted in applications with effective dose values of below 1 mSv. In general, a
      trend towards lower dose values based on technical innovations has to be
      acknowledged. Effective dose values are down to clearly below 10 mSv on average,
      and there are a number of applications such as cardiac and pediatric CT which are
      performed routinely below 1 mSv on modern equipment. 

PMID- 24434791
TI  - Widespread differences in cortex DNA methylation of the "language gene" CNTNAP2
      between humans and chimpanzees.
AB  - CNTNAP2, one of the largest genes in the human genome, has been linked to human
      specific language abilities and neurodevelopmental disorders. Our hypothesis is
      that epigenetic rather than genetic changes have accelerated the evolution of the
      human brain. To compare the cortex DNA methylation patterns of human and
      chimpanzee CNTNAP2 at ultra-high resolution, we combined methylated DNA
      immunoprecipitation (MeDIP) with NimbleGen tiling arrays for the orthologous gene
      and flanking sequences. Approximately 1.59 Mb of the 2.51 Mb target region could
      be aligned and analyzed with a customized algorithm in both species. More than
      one fifth (0.34 Mb) of the analyzed sequence throughout the entire gene displayed
      significant methylation differences between six human and five chimpanzee
      cortices. One of the most striking interspecies differences with 28% methylation
      in human and 59% in chimpanzee cortex (by bisulfite pyrosequencing) lies in a
      region 300 bp upstream of human SNP rs7794745 which has been associated with
      autism and parent-of-origin effects. Quantitative real-time RT PCR revealed that
      the protein-coding splice variant CNTNAP2-201 is 1.6-fold upregulated in human
      cortex, compared with the chimpanzee. Transcripts CNTNAP2-001, -002, and -003 did
      not show skewed allelic expression, which argues against CNTNAP2 imprinting, at
      least in adult human brain. Collectively, our results suggest widespread cortex
      DNA methylation changes in CNTNAP2 since the human-chimpanzee split, supporting a
      role for CNTNAP2 fine-regulation in human-specific language and communication
      traits. 

PMID- 24434793
TI  - Host-defense peptides with therapeutic potential from skin secretions of frogs
      from the family pipidae.
AB  - Skin secretions from frogs belonging to the genera Xenopus, Silurana,
      Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of
      host-defense peptides with varying degrees of antimicrobial activities and
      cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide
      (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF)
      peptides have been isolated from norepinephrine-stimulated skin secretions from
      several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins
      have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A
      major obstacle to the development of these peptides as anti-infective agents is
      their hemolytic activities against human erythrocytes. Analogs of the magainins,
      CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low
      cytotoxicities have been developed that are active (MIC < 5 MUM) against
      multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli,
      Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae.
      Despite this, the therapeutic potential of frog skin peptides as anti-infective
      agents has not been realized so that alternative clinical applications as anti
      cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored. 

PMID- 24434794
TI  - Clinical potential of oral nicorandil to improve myocardial fatty acid metabolism
      after percutaneous coronary intervention in hemodialysis patients.
AB  - BACKGROUND/AIMS: The assessment of myocardial fatty acid metabolism impairment by
      single-photon emission computed tomography (SPECT) using (123)I-beta
      methyliodophenyl-pentadecanoic acid (BMIPP) might predict the risk of cardiac
      death in hemodialysis patients. We investigated the potential of oral nicorandil
      to improve myocardial fatty acid metabolism after percutaneous coronary
      intervention (PCI) in this population. METHODS: We evaluated 128 hemodialysis
      patients who had obtained coronary revascularization by PCI (90 men and 38 women,
      66 +/- 9 years). Participants for the analysis were randomly assigned to either
      the nicorandil (n = 63) or control group (n = 65). BMIPP SPECT was performed
      every year after coronary revascularization by PCI. Uptake on SPECT was graded in
      17 segments on a 5-point scale (0, normal; 4, absent) and assessed as BMIPP
      summed scores (SS). RESULTS: The incidence of cardiac death was lower (p = 0.004)
      in the nicorandil group (7/63, 11.1%) than in the control group (21/65, 32.3%)
      during a mean follow-up of 2.7 +/- 1.4 years. BMIPP SS reduction rates improved
      in the nicorandil group compared with the control group from 3 years of
      administration. In Kaplan-Meier analyses, free survival rate of cardiac death was
      higher in patients with a >=20% BMIPP SS reduction rate as compared with those
      with a <20% BMIPP SS reduction rate (p = 0.0001). In multiple logistic analysis,
      oral administration of nicorandil was associated with >=20% reduction rates of
      BMIPP SS (odds ratio 2.823, p = 0.011). CONCLUSION: Long-term oral administration
      of nicorandil may improve impaired myocardial fatty acid metabolism after
      coronary revascularization by PCI in hemodialysis patients.

PMID- 24434795
TI  - Seeing is believing: dynamic changes in renal epithelial autophagy during injury
      and repair.
AB  - Ischemic injury to the kidneys is a prevalent clinical problem, contributing
      importantly to chronic kidney disease. Yet, underlying molecular mechanisms are
      elusive. To address the possible role of autophagy, we engineered a novel strain
      of mice harboring a ubiquitously expressed CAG-RFP-EGFP-LC3 transgene. Using this
      tool, we examined the post-ischemic kidney and detailed the dynamics of renal
      tubular epithelial autophagy. In addition, we defined the role of MTOR in the
      resolution of autophagy during epithelial survival and kidney repair. 

PMID- 24434797
TI  - Differential expression of cardiac uncoupling proteins 2 and 3 in response to
      myocardial ischemia-reperfusion in rats.
AB  - AIMS: We aimed to evaluate the transcription and translation of genes for
      uncoupling protein 2 (UCP2) & uncoupling protein 3 (UCP3) in rat heart
      mitochondria of both ventricles after myocardial ischemia followed by various
      periods of reperfusion. MAIN METHODS: Seven groups of 8 male Wistar rats were
      evaluated for the effects of ischemia and also reperfusion, using Western blot of
      isolated mitochondrial proteins in addition to RNA extraction followed by real
      time RT-PCR analysis. KEY FINDINGS: In rats with 30 min of reperfusion (R30) UCP2
      protein was increased 213+/-33%, which is meaningfully more than the control
      group (P<0.001). Western blot showed increase in UCP2 protein level in groups
      receiving reperfusion for 60 min (R60), 120 min (R120) and 180 min (R180) as much
      as 152+/-28% (P<0.001 vs. control), 123+/-19% (P<0.01 vs. control) and 131+/-30%
      (P<0.01 vs. control), respectively. There was no statistically important
      difference in UCP2 mRNA between either right or left ventricles of ischemic and
      ischemia-reperfusion (IR) groups vs. control group. In the groups R180 and R240,
      UCP3 protein levels showed 131+/-27% and 102+/-18% increase, respectively (both
      P<0.001 vs. control group). However, the change in UCP3 level in other groups was
      not significantly different from the control group. SIGNIFICANCE: UCP2 and UCP3
      protein levels are considerably increased in the ischemic area early after acute
      myocardial IR. The right ventricular UCP2 protein expression does not change,
      that is, effect of IR on UCP2 protein is a local process. However, UCP3 protein
      level increased both in ischemic area of the left ventricle and in non-ischemic
      area of the right ventricle.

PMID- 24434796
TI  - Late dual endothelin receptor blockade with bosentan restores impaired
      cerebrovascular function in diabetes.
AB  - AIMS: Up-regulation of the endothelin (ET) system in type-2 diabetes increases
      contraction and decreases relaxation in basilar artery. We showed that 1) ET
      receptor antagonism prevents diabetes-mediated cerebrovascular dysfunction; and
      2) glycemic control prevents activation of the ET-system in diabetes. Here, our
      goal is to determine whether and to what extent glycemic control or ET-receptor
      antagonism reverses established cerebrovascular dysfunction in diabetes. MAIN
      METHODS: Non-obese type-2 diabetic Goto-Kakizaki rats were administered either
      vehicle, metformin (300 mg/kg/day) or dual ET-receptor antagonist bosentan
      (100mg/kg) for 4-weeks starting at 18-weeks after established cerebrovascular
      dysfunction (n=5-6/group). Control group included vehicle-treated aged-matched
      Wistar rats. Blood glucose and pressure were monitored weekly. At termination,
      basilar arteries were collected and cumulative dose-response curves to ET-1 (0.1
      500 nM), 5-HT (1-1000 nM) and acetylcholine (Ach, 0.1 nM-5 MUM) were studied by
      wire myograph. Middle cerebral artery (MCA) myogenic reactivity and tone were
      measured using pressurized arteriograph. KEY FINDINGS: There was no difference in
      ET-1 and 5-HT-mediated constrictions. Endothelium-dependent relaxation was
      impaired in diabetes. Bosentan improved sensitivity to Ach as well as the maximum
      relaxation. Myogenic-tone is decreased over the course of the disease. Both
      treatments improved the ability of MCAs to develop tone at 80 mm Hg and only
      bosentan improved the tone at higher pressures. SIGNIFICANCE: These results
      suggest that contractile response is not affected by glycemic control or ET
      receptor antagonism. Meanwhile, dual ET-receptor blockade is effective in
      partially improving endothelium-dependent relaxation and myogenic response in a
      blood pressure-independent manner even after established cerebrovascular
      dysfunction and offers therapeutic potential.

PMID- 24434798
TI  - Highly reliable field electron emitters produced from reproducible damage-free
      carbon nanotube composite pastes with optimal inorganic fillers.
AB  - Highly reliable field electron emitters were developed using a formulation for
      reproducible damage-free carbon nanotube (CNT) composite pastes with optimal
      inorganic fillers and a ball-milling method. We carefully controlled the ball
      milling sequence and time to avoid any damage to the CNTs, which incorporated
      fillers that were fully dispersed as paste constituents. The field electron
      emitters fabricated by printing the CNT pastes were found to exhibit almost
      perfect adhesion of the CNT emitters to the cathode, along with good uniformity
      and reproducibility. A high field enhancement factor of around 10,000 was
      achieved from the CNT field emitters developed. By selecting nano-sized metal
      alloys and oxides and using the same formulation sequence, we also developed
      reliable field emitters that could survive high-temperature post processing.
      These field emitters had high durability to post vacuum annealing at 950  degrees
      C, guaranteeing survival of the brazing process used in the sealing of field
      emission x-ray tubes. We evaluated the field emitters in a triode configuration
      in the harsh environment of a tiny vacuum-sealed vessel and observed very
      reliable operation for 30 h at a high current density of 350 mA cm(-2). The CNT
      pastes and related field emitters that were developed could be usefully applied
      in reliable field emission devices.

PMID- 24434799
TI  - Surgical models for cardiac regeneration in neonatal mice.
AB  - Although amphibian and fish models of heart regeneration have existed for
      decades, a mammalian equivalent has long remained elusive. Our discovery of a
      brief postnatal window for heart regeneration in neonatal mice has led to the
      establishment of surgical models for cardiac regenerative studies in mammals for
      the first time. This protocol describes a 10-min surgical procedure to induce
      cardiac injury in 1-d-old neonatal mice. This allows for the analysis of cardiac
      regeneration after surgical amputation of the left ventricle (LV) (apical
      resection) and coronary artery occlusion (myocardial infarction (MI)). A
      comparative analysis of neonatal and adult responses to myocardial injury should
      enable identification of the key differences between regenerative and
      nonregenerative responses to cardiac injury. This protocol can also be adapted to
      the growing repertoire of genetic models available in the mouse, and it provides
      a valuable tool for unlocking the molecular mechanisms that guide mammalian heart
      regeneration during early postnatal life. 

PMID- 24434800
TI  - Isolation of plasma membrane-associated membranes from rat liver.
AB  - Dynamic interplay between intracellular organelles requires a particular
      functional apposition of membrane structures. The organelles involved come into
      close contact, but do not fuse, thereby giving rise to notable microdomains;
      these microdomains allow rapid communication between the organelles. Plasma
      membrane-associated membranes (PAMs), which are microdomains of the plasma
      membrane (PM) interacting with the endoplasmic reticulum (ER) and mitochondria,
      are dynamic structures that mediate transport of proteins, lipids, ions and
      metabolites. These structures have gained much interest lately owing to their
      roles in many crucial cellular processes. Here we provide an optimized protocol
      for the isolation of PAM, PM and ER fractions from rat liver that is based on a
      series of differential centrifugations, followed by the fractionation of crude PM
      on a discontinuous sucrose gradient. The procedure requires ~8-10 h, and it can
      be easily modified and adapted to other tissues and cell types. 

PMID- 24434801
TI  - Imaging pericytes and capillary diameter in brain slices and isolated retinae.
AB  - The cerebral circulation is highly specialized, both structurally and
      functionally, and it provides a fine-tuned supply of oxygen and nutrients to
      active regions of the brain. Our understanding of blood flow regulation by
      cerebral arterioles has evolved rapidly. Recent work has opened new avenues in
      microvascular research; for example, it has been demonstrated that contractile
      pericytes found on capillary walls induce capillary diameter changes in response
      to neurotransmitters, suggesting that pericytes could have a role in
      neurovascular coupling. This concept is at odds with traditional models of brain
      blood flow regulation, which assume that only arterioles control cerebral blood
      flow. The investigation of mechanisms underlying neurovascular coupling at the
      capillary level requires a range of approaches, which involve unique technical
      challenges. Here we provide detailed protocols for the successful physiological
      and immunohistochemical study of pericytes and capillaries in brain slices and
      isolated retinae, allowing investigators to probe the role of capillaries in
      neurovascular coupling. This protocol can be completed within 6-8 h; however,
      immunohistochemical experiments may take 3-6 d. 

PMID- 24434802
TI  - Transcriptome-wide target profiling of RNA cytosine methyltransferases using the
      mechanism-based enrichment procedure Aza-IP.
AB  - Cytosine methylation within RNA is common, but its full scope and functions are
      poorly understood, as the RNA targets of most mammalian cytosine RNA
      methyltransferases (m(5)C-RMTs) remain uncharacterized. To enable their
      characterization, we developed a mechanism-based method for transcriptome-wide
      m(5)C-RMT target profiling. All characterized mammalian m(5)C-RMTs form a
      reversible covalent intermediate with their cytosine substrate-a covalent linkage
      that is trapped when conducted on the cytosine analog 5-azacytidine (5-aza-C). We
      used this property to develop Aza-immunoprecipitation (Aza-IP), a methodology to
      form stable m(5)C-RMT-RNA linkages in cell culture, followed by IP and high
      throughput sequencing, to identify direct RNA substrates of m(5)C-RMTs.
      Remarkably, a cytosine-to-guanine (C->G) transversion occurs specifically at
      target cytosines, allowing the simultaneous identification of the precise target
      cytosine within each RNA. Thus, Aza-IP reports only direct RNA substrates and the
      C->G transversion provides an important criterion for target cytosine
      identification, which is not available in alternative approaches. Here we present
      a step-by-step protocol for Aza-IP and downstream analysis, designed to reveal
      identification of substrate RNAs and precise cytosine targets of m(5)C-RMTs. The
      entire protocol takes 40-50 d to complete. 

PMID- 24434804
TI  - Precise determination of seawater calcium using isotope dilution inductively
      coupled plasma mass spectrometry.
AB  - We describe a method for rapid, precise and accurate determination of calcium ion
      (Ca(2+)) concentration in seawater using isotope dilution inductively coupled
      plasma mass spectrometry (ID-ICP-MS). A 10 MUL aliquot of seawater was spiked
      with an appropriate (43)Ca enriched solution for (44)Ca/(43)Ca ID-ICP-MS
      analyses, using an Element XR (Thermo Fisher Scientific), operated at low
      resolution in E-scan acquisition mode. A standard-sample bracketing technique was
      applied to correct for potential mass discrimination and ratio drift at every 5
      samples. A precision of better than 0.05% for within-run and 0.10% for duplicate
      measurements of the IAPSO seawater standard was achieved using 10 MUL solutions
      with a measuring time less than 3 minutes. Depth profiles of seawater samples
      collected from the Arctic Ocean basin were processed and compared with results
      obtained by the classic ethylene glycol tetra-acetic acid (EGTA) titration. Our
      new ID-ICP-MS data agreed closely with the conventional EGTA data, with the
      latter consistently displaying 1.5% excess Ca(2+) values, possibly due to a
      contribution of interference from Mg(2+) and Sr(2+) in the EGTA titration. The
      newly obtained Sr/Ca profiles reveal sensitive water mass mixing in the upper
      oceanic column to reflect ice melting in the Arctic region. This novel technique
      provides a tool for seawater Ca(2+) determination with small sample size, high
      throughput, excellent internal precision and external reproducibility. 

PMID- 24434803
TI  - Universal sample preparation method integrating trichloroacetic acid/acetone
      precipitation with phenol extraction for crop proteomic analysis.
AB  - Crop plants contain large amounts of secondary compounds that interfere with
      protein extraction and gel-based proteomic analysis. Thus, a protein extraction
      protocol that can be easily applied to various crop materials with minimal
      optimization is essential. Here we describe a universal protocol for total
      protein extraction involving trichloroacetic acid (TCA)/acetone precipitation
      followed by SDS and phenol extraction. Through SDS extraction, the proteins
      precipitated by the TCA/acetone treatment can be fully resolubilized and then
      further purified by phenol extraction. This protocol combines TCA/acetone
      precipitation, which aggressively removes nonprotein compounds, and phenol
      extraction, which selectively dissolves proteins, resulting in effective
      purification of proteins from crop tissues. This protocol can also produce high
      quality protein preparations from various recalcitrant tissues, and therefore it
      has a wide range of applications in crop proteomic analysis. Designed to run on a
      small scale, this protocol can be completed within 5 h. 

PMID- 24434805
TI  - Dietary live yeast alters metabolic profiles, protein biosynthesis and thermal
      stress tolerance of Drosophila melanogaster.
AB  - The impact of nutritional factors on insect's life-history traits such as
      reproduction and lifespan has been excessively examined; however, nutritional
      determinant of insect's thermal tolerance has not received a lot of attention.
      Dietary live yeast represents a prominent source of proteins and amino acids for
      laboratory-reared drosophilids. In this study, Drosophila melanogaster adults
      were fed on diets supplemented or not with live yeast. We hypothesized that
      manipulating nutritional conditions through live yeast supplementation would
      translate into altered physiology and stress tolerance. We verified how live
      yeast supplementation affected body mass characteristics, total lipids and
      proteins, metabolic profiles and cold tolerance (acute and chronic stress).
      Females fed with live yeast had increased body mass and contained more lipids and
      proteins. Using GC/MS profiling, we found distinct metabolic fingerprints
      according to nutritional conditions. Metabolite pathway enrichment analysis
      corroborated that live yeast supplementation was associated with amino acid and
      protein biosyntheses. The cold assays revealed that the presence of dietary live
      yeast greatly promoted cold tolerance. Hence, this study conclusively
      demonstrates a significant interaction between nutritional conditions and thermal
      tolerance. 

PMID- 24434806
TI  - Brainstem mechanisms controlling cardiovascular reflexes in channel catfish.
AB  - Microinjections of kynurenic acid and kainic acid into the general visceral
      nucleus (nGV), homologous to the mammalian nucleus tractus solitarius of the
      medulla, in anesthestized, spontaneously breathing catfish were used to identify
      central areas and mechanisms controlling resting normoxic heart rate and blood
      pressure and the cardiovascular responses to hypoxia. Kynurenic acid, an
      antagonist of ionotropic glutamate receptors, significantly reduced resting
      normoxic heart rate but did not block the bradycardia associated with aquatic
      hypoxia. Kainic acid (an excitotoxic glutamatergic receptor agonist) also
      significantly reduced normoxic heart rate, but blocked the hypoxia-induced
      bradycardia. Neither kynurenic acid nor kainic acid microinjections affected
      blood pressure in normoxia or hypoxia. The results of this study indicate that
      glutamatergic receptors in the nGV are involved in the maintenance of resting
      heart rate and the destruction of these neurons with kainic acid abolishes the
      bradycardia associated with aquatic hypoxia. 

PMID- 24434807
TI  - Experimental and theoretical study of the electronic properties of Cu-doped
      anatase TiO2.
AB  - A good correlation was obtained between the electronic properties of Cu-doped
      anatase TiO2 by virtue of both physical chemistry characterization and
      theoretical calculations. Pure and Cu-doped TiO2 were synthesized. The
      composition, structural and electronic properties, and the band gap energy were
      obtained using several techniques. The method of synthesis used produces Cu-doped
      anatase TiO2, and XRD, XPS and Raman spectroscopy indicate that Cu atoms are
      incorporated in the structure by substitution of Ti atoms, generating a
      distortion of the structure and oxygen vacancies. In turn, the band gap energy of
      the synthesized samples decrease drastically with the Cu doping. Moreover,
      periodic density functional theory (DFT-periodic) calculations were carried out
      both to model the experimentally observed doped structures and to understand
      theoretically the experimental structures obtained, the formation of oxygen
      vacancies and the values of the band gap energy. From the analysis of density of
      states (DOS), projected density of states (PDOS) and the electron localization
      function (ELF) a decrease in the band gap is predicted upon increasing the Cu
      doping. Thus, the inclusion of Cu in the anatase structure implies a covalent
      character in the Cu-O interaction, which involves the appearance of new states in
      the valence band maximum with a narrowing in the band gap. 

PMID- 24434809
TI  - Comparative structural and functional analysis of genes encoding pectin
      methylesterases in Phytophthora spp.
AB  - We have scanned the Phytophthora infestans, P. ramorum, and P. sojae genomes for
      the presence of putative pectin methylesterase genes and conducted a sequence
      analysis of all gene models found. We also searched for potential regulatory
      motifs in the promoter region of the proposed P. infestans models, and
      investigated the gene expression levels throughout the course of P. infestans
      infection on potato plants, using in planta and detached leaf assays. We found
      that genes located on contiguous chromosomal regions contain similar motifs in
      the promoter region, indicating the possibility of a shared regulatory mechanism.
      Results of our investigations also suggest that, during the pathogenicity
      process, the expression levels of some of the analyzed genes vary considerably
      when compared to basal expression observed in in vitro cultures of non
      sporulating mycelium. These results were observed both in planta and in detached
      leaf assays.

PMID- 24434808
TI  - Potential of compressed sensing in quantitative MR imaging of cancer.
AB  - Classic signal processing theory dictates that, in order to faithfully
      reconstruct a band-limited signal (e.g., an image), the sampling rate must be at
      least twice the maximum frequency contained within the signal, i.e., the Nyquist
      frequency. Recent developments in applied mathematics, however, have shown that
      it is often possible to reconstruct signals sampled below the Nyquist rate. This
      new method of compressed sensing (CS) requires that the signal have a concise and
      extremely dense representation in some mathematical basis. Magnetic resonance
      imaging (MRI) is particularly well suited for CS approaches, owing to the
      flexibility of data collection in the spatial frequency (Fourier) domain
      available in most MRI protocols. With custom CS acquisition and reconstruction
      strategies, one can quickly obtain a small subset of the full data and then
      iteratively reconstruct images that are consistent with the acquired data and
      sparse by some measure. Successful use of CS results in a substantial decrease in
      the time required to collect an individual image. This extra time can then be
      harnessed to increase spatial resolution, temporal resolution, signal-to-noise,
      or any combination of the three. In this article, we first review the salient
      features of CS theory and then discuss the specific barriers confronting CS
      before it can be readily incorporated into clinical quantitative MRI studies of
      cancer. We finally illustrate applications of the technique by describing
      examples of CS in dynamic contrast-enhanced MRI and dynamic susceptibility
      contrast MRI. 

PMID- 24434810
TI  - Two novel mutations in glucocerebrosidase, C23W and IVS7-1 G>A, identified in
      Type 1 Gaucher patients heterozygous for N370S.
AB  - Gaucher disease is an autosomal recessive lysosomal storage disorder resulting
      from deficient glucocerebrosidase activity. There have been nearly 300 mutations
      described to date. Novel mutations can potentially provide insight into the
      biochemical basis of the disease. Two novel mutations are described in two Type 1
      Gaucher patients with N370S compound heterozygosity; a point mutation that causes
      an amino acid substitution at cysteine residue 23 for tryptophan, and a second
      point mutation within the splicing element at the 3' end of intron 7. Both
      mutations were identified by PCR amplification and sequence analysis of patient
      glucocerebrosidase genomic DNA. Restriction fragment length polymorphism analysis
      was established for both novel mutations for efficient identification in future
      patients. Past literature suggests that mutations affecting cysteine residues
      involved in disulfide bridges, as well as mutations affecting splicing patterns
      of the glucocerebrosidase transcript, are detrimental to enzyme activity.
      However, compound heterozygosity with N370S, a mild mutation, will lead to a mild
      phenotype. The cases reported here support these past findings. 

PMID- 24434811
TI  - The association of interleukin-21 polymorphisms with interleukin-21 serum levels
      and risk of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with
      complex genetic components. Interleukin-21 (IL-21) is the most recently
      discovered member of the type-I cytokine family, which has a variety of effects
      on the immune system, including B cell activation, plasma cell differentiation,
      and immunoglobulin production. Previous studies have identified that IL-21 was
      associated with different autoimmune and inflammatory diseases, such as
      rheumatoid arthritis, multiple sclerosis and SLE. Variations in the DNA sequence
      in the IL-21 gene may lead to altered IL-21 production and/or activity, and thus
      this can modulate an individual's susceptibility to SLE. To test this hypothesis,
      we investigated the association of the IL-21 polymorphisms and its serum levels
      with the risk of SLE in a Chinese population. We analyzed three single nucleotide
      polymorphisms of IL-21 gene rs907715 C/T, rs2221903 T/C and rs2055979 C/A in 175
      patients with SLE and 190 age- and sex-matched controls, using Snapshot SNP
      genotyping assays and DNA sequencing method. Soluble IL-21 (sIL-21) levels were
      measured by ELISA. There were significant differences in the genotype and allele
      frequencies of IL-21 gene rs2055979 C/A polymorphism between the group of
      patients with SLE and the control group (P<0.05). sIL-21 levels were increased in
      patients with SLE compared with controls (P<0.01). Moreover, genotypes carrying
      the IL-21 rs2055979 A variant allele were associated with increased IL-21 levels
      compared to the homozygous wild-type genotype in patients with SLE. The rs2055979
      C/A polymorphism of IL-21 and its sIL-21 levels were associated with SLE in the
      Chinese population. Our data suggests that IL-21 gene may play a role in the
      development of SLE.

PMID- 24434812
TI  - Unusual maternal uniparental isodisomic x chromosome mosaicism with asymmetric y
      chromosomal rearrangement.
AB  - Infertile men with azoospermia commonly have associated microdeletions in the
      azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or
      sex chromosome rearrangements. In this study, we describe an unusual 46,XX and
      45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal
      male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pter
      >q11.222::p11.2->pter)[25]. The derivative Y chromosome had a deletion at
      Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed
      by fluorescence in situ hybridization analysis, and complete deletion of the AZFb
      and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X
      chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and
      derived from the maternal gamete, as determined by examination of short tandem
      repeat markers. We postulate that the derivative Y chromosome might have been
      generated during paternal meiosis or early embryogenesis. Also, we suggest that
      the very rare mosaicism of isodisomic X chromosomes might be formed during
      maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/
      45,X lineage because of the instability of the derivative Y chromosome. To our
      knowledge, this is the first confirmatory study to verify the origin of a sex
      chromosome mosaicism with a Y chromosome rearrangement.

PMID- 24434813
TI  - One-step synthesis of a highly homogeneous SBA-NHC hybrid material: en route to
      single-site NHC-metal heterogeneous catalysts with high loadings.
AB  - The one-step synthesis of a mesoporous silica of SBA type, functionalized with a
      1-(2,6-diisopropylphenyl)-3-propyl-imidazolium (iPr2Ar-NHC-propyl) cation located
      in the pore channels, is described. This material was obtained by the direct
      hydrolysis and co-condensation of tetraethylorthosilicate (TEOS) and 1-(2,6
      diisopropylphenyl)-3-[3-(triethoxysilyl)propyl]-imidazolium iodide in the
      presence of Pluronic P123 as a non-ionic structure-directing agent and aqueous
      HCl (37%) as an acid catalyst. Small-angle X-ray diffraction measurements,
      scanning and transmission electron microscopies, as well as dinitrogen sorption
      analyses revealed that the synthesized material is highly mesoporous with a 2D
      hexagonal arrangement of the porous network. (13)C and (29)Si CP-MAS NMR
      spectroscopy confirmed that the material contains intact iPr2Ar-NHC-propyl
      cations, which are covalently anchored via silicon atoms fused into the silica
      matrix. Moreover, comparison of the latter data with those of an analogous post
      synthetic grafted SBA-NHC material allowed us to establish that, as expected, (i)
      it is most probably more homogeneous and (ii) it shows a more robust anchoring of
      the organic units. Finally, elemental mapping by energy dispersive X-ray
      spectroscopy in the scanning electron microscope demonstrated a very homogeneous
      distribution of the imidazolium units within the one-pot material, moreover with
      a high content. This study thus demonstrates that a relatively bulky and
      hydrophilic imidazolium unit can be directly co-condensed with TEOS in the
      presence of a structure-directing agent to provide in a single step a highly
      ordered and homogeneous mesoporous hybrid SBA-NHC material, possessing a
      significant number of cationic NHC sites. 

PMID- 24434814
TI  - Identification of three novel mutations in the FRMD7 gene for X-linked idiopathic
      congenital nystagmus.
AB  - Idiopathic congenital nystagmus (ICN) consists of involuntary and periodic ocular
      motility, often with seriously reduced visual acuity. To identify the genetic
      defects associated with X-linked ICN, we performed PCR-based DNA direct
      sequencing of two candidate genes, FRMD7 and GPR143, in four families. Mutation
      analysis led to identification of three novel mutations, p.S260R, p.Q487X, and
      p.V549Y fsX554, in FRMD7 in three of the recruited families. Results from
      structural modeling indicated that the p.S260R may potentially disrupt FRMD7
      function through loss of a phosphorylation site and/or interference with protein
      protein interactions. Both p.Q487X, and p.V549Y fsX554 mutations were predicted
      to generate nonfunctional truncated proteins. Using a capture next generation
      sequencing method, we excluded CASK as the responsible gene for the remaining
      family. Combining sequence analysis and structural modeling, we report three
      novel mutations in FRMD7 in three independent families with XLICN, and provide
      molecular insights for future XLICN diagnosis and treatment. 

PMID- 24434816
TI  - Changes in the electrical properties of the electrode-skin-underlying tissue
      composite during a week-long programme of neuromuscular electrical stimulation.
AB  - Particular neuromuscular electrical stimulation (NMES) applications require the
      use of the same electrodes over a long duration (>1 day) without having access to
      them. Under such circumstance the quality of the electrode-skin contact cannot be
      assessed. We used the NMES signal itself to assess the quality of the electrode
      skin contact and the electrical properties of the underlying tissues over a week.
      A 14% decrease in the skin's stratum corneum resistance (from 20 to 17 kOmega)
      and a 15% decrease in the resistance of the electrodes and underlying tissues
      (from 550 to 460 Omega) were observed in the 14 healthy subjects investigated. A
      follow-on investigation of the effect of exercise-induced sweating on the
      electrical properties of the electrode-skin-underlying tissue composite during
      NMES indicated a correlation between the decrease in the resistance values
      observed over the course of the week and the accumulation of sweat at the
      electrode-skin interface. The value of the capacitance representing the
      dielectric properties of the skin's stratum corneum increased after exercise
      induced sweating but did not change significantly over the course of the week. We
      conclude that valuable information about the electrode-skin-underlying tissue
      composite can be gathered using the NMES signal itself, and suggest that this is
      a practical, safe and relatively simple method for monitoring these electrical
      properties during long-term stimulation. 

PMID- 24434818
TI  - Analysis of an asymmetric two-strain dengue model.
AB  - In this paper we analyse a two-strain compartmental dengue fever model that
      allows us to study the behaviour of a Dengue fever epidemic. Dengue fever is the
      most common mosquito-borne viral disease of humans that in recent years has
      become a major international public health concern. The model is an extension of
      the classical compartmental susceptible-infected-recovered (SIR) model where the
      exchange between the compartments is described by ordinary differential equations
      (ode). Two-strains of the virus exist so that a primary infection with one strain
      and secondary infection by the other strain can occur. There is life-long
      immunity to the primary infection strain, temporary cross-immunity and after the
      secondary infection followed by life-long immunity, to the secondary infection
      strains. Newborns are assumed susceptible. Antibody Dependent Enhancement (ade)
      is a mechanism where the pre-existing antibodies to the previous dengue infection
      do not neutralize but rather enhance replication of the secondary strain. In the
      previously studied models the two strains are identical with respect to their
      epidemiological functioning: that is the epidemiological process parameters of
      the two strains were assumed equal. As a result the mathematical model possesses
      a mathematical symmetry property. In this manuscript we study a variant with
      epidemiological asymmetry between the strains: the force of infection rates
      differ while all other epidemiological parameters are equal. Comparison with the
      results for the epidemiologically symmetric model gives insight into its
      robustness. Numerical bifurcation analysis and simulation techniques including
      Lyapunov exponent calculation will be used to study the long-term dynamical
      behaviour of the model. For the single strain system stable endemic equilibria
      exist and for the two-strain system endemic equilibria, periodic solutions and
      also chaotic behaviour. 

PMID- 24434819
TI  - Transcriptional response of Enterococcus faecalis to sunlight.
AB  - Microarrays were used to investigate the transcriptional response of Enterococcus
      faecalis to photostress. E. faecalis are Gram-positive bacteria used as
      indicators of water quality and have been shown to vary diurnally in response to
      sunlight. E. faecalis in filtered seawater microcosms were exposed to artificial
      sunlight for 12h and then placed in the dark for 12h. Transcript abundance was
      measured at 0, 2, 6, 12, and 24h in the sunlit microcosm and a dark control using
      microarrays. Culturable E. faecalis concentrations decreased 6-7 orders of
      magnitude within the first 6h of light exposure. After 12h in the dark, no
      evidence of dark-repair was observed. Expression data collected after 12h of
      sunlight exposure revealed a difference in transcript abundance in the light
      relative to dark microcosms for 35 unique ORFs, 33 ORFs showed increased
      transcript abundance and 2 ORFs showed reduced transcript abundance. A majority
      (51%) of the ORFs with increased transcript abundance in the sunlit relative to
      dark microcosms encoded hypothetical proteins; others were associated with
      protein synthesis, oxidative stress and DNA repair. Results suggest that E.
      faecalis exposed to sunlight actively transcribe RNA in response to photostress. 

PMID- 24434817
TI  - Glutathione transferase mu 2 protects glioblastoma cells against aminochrome
      toxicity by preventing autophagy and lysosome dysfunction.
AB  - U373MG cells constitutively express glutathione S-transferase mu 2 (GSTM2) and
      exhibit (3)H-dopamine uptake, which is inhibited by 2 uM of nomifensine and 15 uM
      of estradiol. We generated a stable cell line (U373MGsiGST6) expressing an siRNA
      against GSTM2 that resulted in low GSTM2 expression (26% of wild-type U373MG
      cells). A significant increase in cell death was observed when U373MGsiGST6 cells
      were incubated with 50 uM purified aminochrome (18-fold increase) compared with
      wild-type cells. The incubation of U373MGsiGST6 cells with 75 uM aminochrome
      resulted in the formation of autophagic vacuoles containing undigested cellular
      components, as determined using transmission electron microscopy. A significant
      increase in autophagosomes was determined by measuring endogenous LC3-II, a
      significant decrease in cell death was observed in the presence of bafilomycin A
      1, and a significant increase in cell death was observed in the presence of
      trehalose. A significant increase in LAMP2 immunostaining was observed, a
      significant decrease in bright red fluorescence of lysosomes with acridine orange
      was observed, and bafilomycin A 1 pretreatment reduced the loss of lysosome
      acidity. A significant increase in cell death was observed in the presence of
      lysosomal protease inhibitors. Aggregation of TUBA/alpha-tubulin (tubulin, alpha)
      and SQSTM1 protein accumulation were also observed. Moreover, a significant
      increase in the number of lipids droplets was observed compared with U373MG cells
      with normal expression of GSTM2. These results support the notion that GSTM2 is a
      protective enzyme against aminochrome toxicity in astrocytes and that aminochrome
      cell death in U373MGsiGST6 cells involves autophagic-lysosomal dysfunction. 

PMID- 24434820
TI  - Does knowledge of coronary artery calcium affect cardiovascular risk perception,
      likelihood of taking action, and health-promoting behavior change?
AB  - BACKGROUND: Evidence indicates that a healthy lifestyle can reduce cardiovascular
      disease risk, yet many people engage in unhealthy behaviors. New technologies
      such as coronary artery calcium (CAC) screening detect atherosclerosis before
      clinical disease is manifested. Knowledge of an abnormal finding could provide
      the "teachable moment" to enhance motivation for change. OBJECTIVE: The aim of
      this study was to examine how knowledge of CAC score affects risk perception,
      likelihood of taking action, and health-promoting behavior change in persons at
      high risk for cardiovascular disease. METHODS: This study used a descriptive
      prospective design with 174 high-risk adults (>=3 major risk factors) recruited
      at a radiology center offering CAC scans. Baseline self-report surveys using the
      Perception of Risk of Heart Disease Scale, the Benefits and Barriers Scale, the
      Quality of Life Index, and the Health-Promoting Lifestyle Profile II were
      completed immediately after a screening CAC scan but before results were known.
      Follow-up occurred 3 months later using mailed packets. RESULTS: Participants'
      mean age was 58 years; 62% were men, 89% were white, and most were well educated.
      There was no significant change in risk perception scores over time or between
      groups, except for a positive interaction in the moderate-risk group (CAC scores
      of 101-400) (P = .004). Quality of life remained unchanged. Health-promoting
      behavior changes increased in all groups over time (P < .001). McNemar chi2
      analysis indicated that risk reduction medication use increased in all groups,
      with a significant increase in statin (P < .001) and aspirin (P < .001) intake.
      Predictors of behavior change were perceived barriers (beta = -.41; P < .001) and
      quality of life (beta = .44; P < .001). CONCLUSIONS: Knowledge of CAC score does
      impact risk perception for some at-risk groups. This knowledge does enhance
      motivation for behavior change. Knowledge of CAC score does not impact quality of
      life. It is hoped that through improved understanding of the effect of CAC
      scoring on behavior change, nurses can better assist patients to modify behaviors
      during teachable moments.

PMID- 24434821
TI  - Family context influences psychological outcomes of depressive symptoms and
      emotional quality of life in patients with heart failure.
AB  - BACKGROUND: Although family influences in heart failure (HF) care are considered
      important, little evidence is available regarding relationships between the
      family context and specific outcomes for patients with HF. OBJECTIVE: The aim of
      this study was to examine the relationships of patient perceptions of family
      functioning, autonomy support, and perceived criticism, as well as their family
      member's (FM) HF knowledge, with patient outcomes of depressive symptoms and HF
      quality of life (QOL). METHODS: Participants (n = 117) with HF were enrolled in a
      family partnership intervention study. Self-report questionnaires measuring the
      HF patient's perceptions of family context and the FM's knowledge were analyzed
      relative to the HF patient's outcomes using correlations and sequential
      multivariate regression analyses. Only preintervention, baseline data are
      reported here. RESULTS: Age, ethnicity, Charlson comorbidity index, global family
      functioning, and FM's HF knowledge accounted for 37.8% (P < .001) of the variance
      in the patient's depressive symptoms. An additional moderating effect of
      ethnicity on the association between global family functioning and patient's
      depressive symptoms was significant (change R2 = 0.06, P = .001), resulting in a
      final model that accounted for 43.3% of depressive symptom variance. Age,
      ethnicity, global family functioning, and autonomy support accounted for 24.9% (P
      < .001) of the variance in emotional HF QOL. An additional moderating effect of
      ethnicity on the association between global family functioning and patient's
      emotional HF QOL was significant (change R2 = 0.05, P = .009), resulting in a
      final model that accounted for 28.9% of emotional QOL variance. CONCLUSIONS: This
      study underscores the importance of the patient's perspective on family
      functioning and autonomy support, along with FM's HF knowledge, on HF patient
      outcomes moderated by ethnicity. Future interventions could target the modifiable
      patient-family context relationships for improving depressive symptoms and QOL in
      HF patients. These findings point to the need for greater family assessment to
      identify those at risk for worse outcomes and to guide family focused
      interventions.

PMID- 24434822
TI  - Translation and validation of the Self-care of Heart Failure Index into Persian.
AB  - BACKGROUND: Chronic heart failure (CHF) is a common burdensome health problem
      worldwide. Self-care improves outcomes in patients with CHF. The Self-care of
      Heart Failure Index (SCHFI) is a well-known scale for assessing self-care. A
      reliable, valid, and culturally acceptable instrument is needed to develop and
      test self-care interventions in Iran. OBJECTIVE: We sought to translate and
      validate the Persian version of SCHFI v 6.2 (pSCHFI). METHODS AND RESULTS: We
      translated the SCHFI into Persian (pSCHFI) using standardized methods. The
      reliability was evaluated by assessing Cronbach's alpha coefficient. Expert
      opinion, discussion with patients, and confirmatory factor analysis were used to
      assess face validity, content validity, and construct validity, respectively. The
      analysis, using 184 participants, showed acceptable internal consistency and
      construct validity for the 3 subscales of pSCHFI-self-care maintenance, self-care
      management, and self-care self-confidence. CONCLUSION: The pSCHFI is a valid
      instrument with an acceptable reliability for evaluating self-care in Persian
      patients with heart failure.

PMID- 24434823
TI  - Transcatheter aortic valve replacement options for severe aortic stenosis in high
      risk patients.
AB  - BACKGROUND: Calcific aortic stenosis has now become the most common valvular
      disease in Western countries. It is a disease of the old and very old. Senile
      calcific aortic stenosis affects 5% of the population 70 years or older in the
      United States. Traditionally, the gold standard for treating aortic stenosis has
      been surgical aortic valve replacement. Unfortunately, surgical aortic valve
      replacement is, in many cases, not a viable option for this patient population.
      PURPOSE: This article examines transcatheter aortic valve replacement as an
      evolving technology and medical procedure with the high-risk and inoperable
      patients in mind. Since then, the geriatric patient population is ever increasing
      and the numbers of severe aortic stenosis cases are expected to increase
      accordingly. It is vital for healthcare professionals to be well informed to give
      competent care. SUMMARY: International research over the last decade has shown
      promising results in improved quality of life with regard to pain, functional
      status, and overall health. This research has expanded to the United States
      within the last few years. Two transcatheter aortic valve systems are available
      for use and are being researched. The Placement of AoRTic TraNscathetER Valve
      Trial (PARTNER trial) (Edwards SAPIEN valve) and the US Pivotal study (Medtronic
      CoreValve) are 2 large studies being conducted, and the medical community is
      anxiously awaiting results. CLINICAL IMPLICATIONS: These complex patients require
      a team approach between the interventional cardiologist, primary cardiologist,
      cardiac surgeons, and highly trained nursing staff. The transcatheter aortic
      valve replacement nurse coordinator is a core member of the team, and the
      contributions of that individual are vital to program success. To avoid
      complications, careful patient selection is important, and a highly trained valve
      clinic coordinator must perform a careful and thorough assessment.

PMID- 24434824
TI  - Construct validity of the Chinese version of the Self-care of Heart Failure Index
      determined using structural equation modeling.
AB  - BACKGROUND: The Self-care of Heart Failure Index (SCHFI) is an empirically tested
      instrument for measuring the self-care of patients with heart failure. OBJECTIVE:
      The aim of this study was to develop a simplified Chinese version of the SCHFI
      and provide evidence for its construct validity. METHODS: A total of 182 Chinese
      with heart failure were surveyed. A 2-step structural equation modeling procedure
      was applied to test construct validity. RESULTS: Factor analysis showed 3 factors
      explaining 43% of the variance. Structural equation model confirmed that self
      care maintenance, self-care management, and self-care confidence are indeed
      indicators of self-care, and self-care confidence was a positive and equally
      strong predictor of self-care maintenance and self-care management. Moreover,
      self-care scores were correlated with the Partners in Health Scale, indicating
      satisfactory concurrent validity. CONCLUSION: The Chinese version of the SCHFI is
      a theory-based instrument for assessing self-care of Chinese patients with heart
      failure.

PMID- 24434825
TI  - Cholesterol screening in US adults and awareness of high cholesterol among
      individuals with severe hypertriglyceridemia: National Health and Nutrition
      Examination Surveys 2001-2008.
AB  - BACKGROUND: Cholesterol screening is an effective method for identifying
      individuals with elevated triglyceride levels. Individuals with severe
      hypertriglyceridemia (SHTG; >=500 mg/dL) have a substantially higher risk for
      developing coronary heart disease and acute pancreatitis than individuals with
      lower triglyceride levels. OBJECTIVE: The aims of this study were to estimate the
      proportion of US adults who reported having their cholesterol checked, to
      evaluate the characteristics associated with having cholesterol checked, and to
      assess factors that are associated with awareness of having high cholesterol
      among adults with SHTG. METHODS: The sample included 7988 adults who participated
      in the National Health and Nutrition Examination Surveys 2001-2008. Polytomous
      logistic regression models were used to identify factors that were associated
      with time since the last cholesterol screening, categorized as never screened,
      screened less than 2 years ago, and screened 2 or more years ago. RESULTS:
      Approximately 71% of the US adults reported ever having their cholesterol
      checked. Only 56% of the individuals with SHTG were aware of having high
      cholesterol. Factors associated with awareness of high cholesterol among those
      with SHTG included obesity, education, having insurance, having diabetes, and
      having a history of cardiovascular events. CONCLUSIONS: Most adults in the United
      States have had their cholesterol checked; however, only half of those with SHTG
      were aware of having high cholesterol. Awareness is the first step in
      implementing strategies to attenuate the health risks associated with
      dyslipidemia.

PMID- 24434826
TI  - Effects of partners together in health intervention on physical activity and
      healthy eating behaviors: a pilot study.
AB  - BACKGROUND: Despite proven efficacy of cardiac rehabilitation (CR) in helping
      patients initiate physical activity and healthy eating changes, less than 50% of
      CR participants maintain changes 6 months later. OBJECTIVE: The objective of this
      feasibility study was to test the Partners Together in Health (PaTH) intervention
      versus usual care in improving physical activity and healthy eating behaviors in
      coronary artery bypass graft surgery patients and their spouses. METHODS: An
      experimental, 2-group (n = 17 couples/group), repeated-measures design was used.
      Coronary artery bypass surgery patients in both groups participated in phase II
      outpatient CR. Spouses in the PaTH group attended CR with the patient and were
      asked to make the same physical activity and healthy eating changes as patients
      did. Spouses in the usual care attended educational classes with patients. It was
      theorized that "2 persons would be better than 1" at making changes and sticking
      with them in the long-term. Physical activity behavior was measured using the
      Actiheart accelerometer; the activity biomarker was an exercise tolerance test.
      Eating behavior was measured using 3-day food records; the biomarker was the
      lipid profile. Data were collected at baseline (entrance in CR), at 3 months
      (post-CR), and at 6 months. Changes over time were examined using Mann-Whitney U
      statistics and effect sizes. RESULTS: The PaTH intervention was successful
      primarily in demonstrating improved trends in healthy eating behavior for
      patients and spouses. No differences were found between the PaTH and usual care
      patients or spouses at 3 or 6 months in the number of minutes per week of
      physical activity. By 6 months, patients in both groups were, on average, below
      the national guidelines for PA recommendations (>=150 min/wk at >3 metabolic
      equivalents). CONCLUSIONS: The couple-focused PaTH intervention demonstrated
      promise in offsetting the decline in dietary adherence typically seen 6 months
      after CR.

PMID- 24434827
TI  - The use of mHealth to deliver tailored messages reduces reported energy and fat
      intake.
AB  - BACKGROUND: Evidence supports the role of feedback in reinforcing motivation for
      behavior change. Feedback that provides reinforcement has the potential to
      increase dietary self-monitoring and enhance attainment of recommended dietary
      intake. OBJECTIVE: The aim of this study was to examine the impact of daily
      feedback (DFB) messages, delivered remotely, on changes in dietary intake.
      METHODS: This was a secondary analysis of the Self- Monitoring And Recording
      using Technology (SMART) Trial, a single-center, 24-month randomized clinical
      trial of behavioral treatment for weight loss. Participants included 210 obese
      adults (mean body mass index, 34.0 kg/m2) who were randomized to either a paper
      diary (PD), personal digital assistant (PDA), or PDA plus daily tailored feedback
      messages (PDA + FB). To determine the role of daily tailored feedback in dietary
      intake, we compared the self-monitoring with DFB group (DFB group; n = 70) with
      the self-monitoring without DFB group (no-DFB group, n = 140). All participants
      received a standard behavioral intervention for weight loss. Self-reported
      changes in dietary intake were compared between the DFB and no-DFB groups and
      were measured at baseline and at 6, 12, 18, and 24 months. Linear mixed modeling
      was used to examine percentage changes in dietary intake from baseline. RESULTS:
      Compared with the no-DFB group, the DFB group achieved a larger reduction in
      energy (-22.8% vs -14.0%; P = .02) and saturated fat (-11.3% vs -0.5%; P = .03)
      intake and a trend toward a greater decrease in total fat intake (-10.4% vs 
      4.7%; P = .09). There were significant improvements over time in carbohydrate
      intake and total fat intake for both groups (P values < .05). CONCLUSION: Daily
      tailored feedback messages designed to target energy and fat intake and delivered
      remotely in real time using mobile devices may play an important role in the
      reduction of energy and fat intake.

PMID- 24434828
TI  - The association between regular symptom monitoring and self-care management in
      patients with heart failure.
AB  - BACKGROUND: Symptom monitoring is considered the first step toward self-care
      management (actions to manage altered symptom status) to avert worsening heart
      failure (HF). However, empirical evidence demonstrating that symptom monitoring
      leads to adequate self-care management is lacking. We examined the relationship
      of adherence to regular symptom monitoring with adequate self-care management in
      HF patients. METHODS AND RESULTS: A total of 311 HF patients (60 years, 35%
      women) were divided into 3 groups by adherence to 2 symptom monitoring behaviors
      (monitoring daily weights and lower extremity edema). Patients who were adherent
      to both symptom monitoring behaviors formed the adherent group (15.1%). Those
      adherent to either of the symptom monitoring behaviors formed the partially
      adherent group (28.9%). Those adherent to neither of the symptom monitoring
      behaviors formed the nonadherent group (56.0%). The adjusted odds of performing
      adequate self-care management were increased by 225% (95% confidence interval,
      1.13-4.48) and 344% (95% confidence interval, 1.55-7.62) for the partially
      adherent and adherent symptom monitoring groups, respectively, compared with the
      nonadherent group. CONCLUSION: Adequacy of self-care management was predicted by
      adherence to symptom monitoring behaviors. This finding suggests that regular
      symptom monitoring facilitates performance of adequate self-care management,
      which may contribute to a decrease in preventable hospitalizations in HF.

PMID- 24434829
TI  - Motivating parents to promote cardiovascular health in children.
AB  - BACKGROUND: Identifying risk factors for cardiovascular disease (CVD) early in
      life gives advanced practice nurses an opportunity to educate parents about
      choices that promote long-term heart health. The addition of universal lipid
      screening to 9- to 11-year-old well-child examinations opens a time interval that
      is adequate for conversations related to cardiovascular health. OBJECTIVE: The
      objective of this study was to determine if the use of a 10-minute health
      promotion plan that includes identification of child modifiable CVD risk factors
      would have an effect on parental intent to engage in lifestyle changes that
      promote heart health in 9- to 11-year-old children. METHODS: The quasi
      experimental pilot study involved 26 English-speaking parents of 9- to 11-year
      old children during routine well-child examinations. Participants completed
      questionnaires before and after receiving a health promotion plan and the child's
      modifiable CVD risk screening results. The advanced practice nurse-researcher
      analyzed the questionnaires to evaluate parental intent to promote lifestyle
      changes. RESULTS: Increases were seen in concern for the child's future heart
      health and in awareness of diet and exercise recommendations. Participants were
      likely to encourage more fruits and vegetables (100%), limit "screen time" (96%),
      encourage physical activity (92%), and limit sugar-sweetened beverage intake
      (96%). Factors identified as most influential on participant decision to
      encourage change were the child's body mass index (38.46%), lipid screening
      results (23.08%), and "other"-tobacco smoke exposure (15.38%), which closely
      approximate national prevalence for each risk category. CONCLUSIONS: The American
      Academy of Pediatrics recommends lipid screening once for all children between 9
      and 11 years of age. In this study, outlining recommendations for good health and
      identifying modifiable CVD risk factors showed a positive effect on parental
      intent to encourage lifestyle changes. Further research is needed to advance the
      science of CVD prevention and risk reduction in children.

PMID- 24434830
TI  - Emotions and health: findings from a randomized clinical trial on
      psychoeducational nursing to patients with implantable cardioverter
      defibrillator.
AB  - BACKGROUND: Serious illness will inevitably lead to a fundamental emotional
      reaction. Traditionally, in interventional treatment or rehabilitation trials,
      the psychological status of patients with implantable cardioverter defibrillators
      has been evaluated with anxiety and depression as outcome measures. In caring for
      these patients, the aim of nursing is to help patients manage life with complex
      heart disease. The early detection and management of negative emotional response
      might prevent the development of pathological conditions such as depression.
      OBJECTIVE: The aims of this study were to (a) describe the trajectory of primary
      emotions over time in patients with implantable cardioverter defibrillators and
      (b) examine the potential effects of psychoeducational nursing on primary
      emotions. METHODS: During the inclusion period (October 2007 to November 2009),
      196 patients with implantable cardioverter defibrillator were randomized (1:1) to
      rehabilitation versus usual care. Rehabilitation consisted of a psychoeducational
      nursing component and an exercise training component. This article concerns phase
      1, psychoeducational nursing, guided by a theory of nursing, Rosemary Rizzo
      Parses Human Becoming Practice Methodologies. The outcome measure is the Emotions
      and Health Scale. The scale consists of 8 primary emotions: joy, agreeableness,
      surprise, fear, sadness, disgust, anger, and anticipation. RESULTS: Mean (SD) age
      was 58 (13) years, and 79% of the participants were men. Significant improvements
      were found in primary emotional responses over time (P < .05) when combining
      groups. However, no difference in emotional intensity was found between the
      groups after 3 months of psychoeducational nursing intervention (P > .05).
      CONCLUSIONS: Primary emotions are affected after implantable cardioverter
      defibrillator implantation. Improvements over time were found. However, it was
      not possible to detect any effect of a short-term psychoeducational nursing
      intervention. Evaluating the primary emotions might be a good way for nurses to
      monitor patients' psychological outcomes because the instrument is sensitive to
      changes over a short period. Further development of early psychoeducational
      nursing interventions for patients with implantable cardioverter defibrillators
      is needed.

PMID- 24434831
TI  - Commentary on "Predictors of heart failure self-care in patients who screened
      positive for mild cognitive impairment".

PMID- 24434832
TI  - Predictors of heart failure self-care in patients who screened positive for mild
      cognitive impairment.
AB  - BACKGROUND: Heart failure (HF) is associated with cognitive impairment, which
      could negatively affect a patient's abilities to carry out self-care, potentially
      resulting in higher hospital readmission rates. Factors associated with self-care
      in patients experiencing mild cognitive impairment (MCI) are not known.
      OBJECTIVE: This descriptive correlation study aimed to assess levels of HF self
      care and knowledge and to determine the predictors of self-care in HF patients
      who screen positive for MCI. METHODS: The Montreal Cognitive Assessment was used
      to screen for MCI. In 125 patients with MCI hospitalized with HF, self-care (Self
      care of Heart Failure Index) and HF knowledge (Dutch Heart Failure Knowledge
      Scale) were assessed. We used multiple regression analysis to test a model of
      variables hypothesized to predict self-care maintenance, management, and
      confidence. RESULTS: Mean (SD) HF knowledge scores (11.24 [1.84]) were above the
      level considered to be adequate (defined as >10). Mean (SD) scores for self-care
      maintenance (63.57 [19.12]), management (68.35 [20.24]), and confidence (64.99
      [16.06]) were consistent with inadequate self-care (defined as scores <70). In
      multivariate analysis, HF knowledge, race, greater disease severity, and social
      support explained 22% of the variance in self-care maintenance (P < .001); age,
      education level, and greater disease severity explained 19% of the variance in
      self-care management (P < .001); and younger age and higher social support
      explained 20% of the variance in self-care confidence scores (P < .001). Blacks,
      on average, scored significantly lower in self-care maintenance (P = .03).
      CONCLUSION: In this sample, patients who screened positive for MCI, on average,
      had adequate HF knowledge yet inadequate self-care scores. These models show the
      influence of modifiable and nonmodifiable predictors for patients who screened
      positive for MCI across the domains of self-care. Health professionals should
      consider screening for MCI and identifying interventions that address HF
      knowledge and social support. Further research is needed to explain the racial
      differences in self-care.

PMID- 24434833
TI  - Perspective on combination RAS blocking therapy: off-TARGET, dis-CORD, MAP-to
      nowhere, low ALTITUDE, and NEPHRON-D.

PMID- 24434834
TI  - Atomic oxygen diffusion on and desorption from amorphous silicate surfaces.
AB  - Surface reactions involving atomic oxygen have attracted much attention in
      astrophysics and astrochemistry, but two of the most fundamental surface
      processes, desorption and diffusion, are not well understood. We studied
      diffusion and desorption of atomic oxygen on or from amorphous silicate surfaces
      under simulated interstellar conditions using a radio-frequency dissociated
      oxygen beam. Temperature programmed desorption (TPD) experiments were performed
      to study the formation of ozone from reaction of atomic and molecular oxygen
      deposited on the surface of a silicate. It is found that atomic oxygen begins to
      diffuse significantly between 40 K and 50 K. A rate equation model was used to
      study the surface kinetics involved in ozone formation experiments. The value of
      atomic oxygen desorption energy has been determined to be 152 +/- 20 meV (1764 +/
      232 K). The newly found atomic oxygen desorption energy, which is much higher
      than the well-accepted value, might explain the discrepancy in abundance of
      molecular oxygen in space between observations and chemical models. 

PMID- 24434835
TI  - Solution-processed Cu2ZnSnS4 superstrate solar cell using vertically aligned ZnO
      nanorods.
AB  - One-dimensional (1D) zinc oxide (ZnO) nanostructures are considered to be
      promising materials for use in thin film solar cells because of their high light
      harvesting and charge collection efficiencies. We firstly report enhanced
      photovoltaic performances in Cu2ZnSnS4 (CZTS) thin film solar cells prepared
      using ZnO nanostructures. A CdS-coated, vertically well-aligned ZnO nanorod (NR)
      array was prepared via a hydrothermal reaction and nanocrystal layer deposition
      (NCLD) and was used as a transparent window/buffer layer in a CZTS thin film
      photovoltaic. A light absorber CZTS thin film was prepared on the CdS/ZnO NRs in
      air by depositing a non-toxic precursor solution that was annealed in two steps
      at temperatures up to 250  degrees C. The crystallized CZTS phase completely
      infiltrated the CdS/ZnO NR array. The nanostructured ZnO array provided improved
      light harvesting behavior compared to a thin film configuration by measuring UV
      vis transmittance spectroscopy. The prepared CZTS/CdS/ZnO NR device exhibited a
      solar energy conversion efficiency of 1.2%, which is the highest efficiency yet
      reported for nanostructured superstrate CZTS solar cells. 

PMID- 24434836
TI  - The role of the home-based provider in disaster preparedness of a vulnerable
      population.
AB  - BACKGROUND: Veterans receiving home-based primary care (HBPC) are an especially
      vulnerable population served by the Veterans Health Administration (VHA) due to
      high rates of physical, functional, and psychological limitations. These
      vulnerabilities may prevent these persons from being adequately prepared for
      disasters. HBPC providers connect the community-dwelling population with their
      regional health care system and thus are appropriate partners for assessing
      preparedness. The limited literature on this topic suggests that there are issues
      with the development and implementation of emergency management plans,
      dissemination to staff, and inconsistencies with preparedness strategies across
      agencies. OBJECTIVE: To further explore identified issues regarding emergency
      management planning for patients receiving medical care in their home, including
      ways in which policy and procedures support the routine assessment of disaster
      preparedness for patients. METHODS: This exploratory pilot project, carried out
      in a single VHA HBPC program located in an urban area, involved seven 15- to 25
      min semistructured interviews with practitioners and leadership. Transcripts of
      the interviews were analyzed using content analysis techniques to develop themes
      to describe information obtained through the interviews. RESULTS: Six themes
      emerged from the data: (1) a national policy regarding the inclusion of disaster
      preparedness assessment in routine HBPC assessment exists in only a skeletal
      manner and individual HBPC programs are tasked with developing their own
      policies; (2) the tools used at the initial assessment were rudimentary and, in
      some cases, individually developed by providers; (3) the comprehension of
      criteria for assigning risk categories (i.e. acuity levels) varied among
      providers; (4) the primary challenges identified by respondents to patient
      engagement in emergency preparedness activities included cognitive impairments,
      patients' willingness to invest in preparedness activities, and limited
      resources; (5) providers received limited formal training on how to prepare their
      patients for a disaster, and (6) provider recommendations included training to
      focus on better strategies to get patients to participate, more consistent time
      spent on patient education, formalization of the initial assessment, and having
      emergency preparedness be formally addressed on a more consistent basis.
      CONCLUSION: Formal standardized strategies regarding disaster preparedness
      assessment for HBPC patients, which leave room for flexibility in consideration
      of local factors, could assist in creating more comprehensive emergency
      management planning agendas and community collaboration.

PMID- 24434837
TI  - Visual detection of biological thiols based on lightening quantum dot-TiO2
      composites.
AB  - The quenched fluorescence of quantum dots (QDs) attached to TiO2 nanoparticles
      was selectively switched on by biothiols through ligand replacement, which makes
      it feasible for facilely sensing biothiols based on the fluorescence turn on
      mechanism. The present sensor exhibited excellent selectivity and high
      sensitivity. Furthermore, a novel fluorescent indicating paper was constructed by
      immobilizing the probe on filter paper to visually detect biothiols in which only
      a UV lamp was used. 

PMID- 24434839
TI  - Pulmonary erythema migrans?

PMID- 24434838
TI  - Correlation of preoperative magnetic resonance imaging of peritoneal
      carcinomatosis and clinical outcome after peritonectomy and HIPEC after 3 years
      of follow-up: preliminary results.
AB  - PURPOSE: In patients with peritoneal carcinomatosis, cytoreductive surgery (CRS)
      and hyperthermic intraperitoneal chemotherapy (HIPEC) is an evolving approach
      with curative intention. Previous studies indicate a correlation between
      preoperative magnetic resonance imaging (MRI) and surgical findings regarding the
      extent of peritoneal carcinomatosis. The aim of this study was to assess
      retrospectively whether preoperative MRI can predict the outcome and is therefore
      a suitable tool for patient selection. MATERIALS AND METHODS: Fifteen patients
      with laparoscopically proven peritoneal carcinomatosis were preoperatively
      examined using a 1.5-T whole-body MRI system. Results were correlated with
      surgical exploration. Follow-up was done by contrast-enhanced abdominal computed
      tomography and, if suspicious for recurring disease, laparoscopy or laparotomy.
      Survival time and interval to recurring disease were correlated with the
      preoperative peritoneal carcinomatosis index (PCI) on MRI (Spearman's rank
      correlation). RESULTS: In five patients radical resection could not be achieved
      (PCI 34 +/- 6.9); survival time was 78.2 +/- 54.1 days. In seven patients
      recurring disease was found 430 +/- 261.2 days after initial complete
      cytoreduction (PCI 11.6 +/- 6.9); survival time was 765.9 +/- 355 days. Two
      patients are still alive after 3 years. Two patients with initially complete
      cytoreduction are without recurring disease after 3 years (PCI 5 and 12). One
      patient was lost for follow-up. CONCLUSIONS: Results of the preoperative MRI
      correlate well with the surgical PCI, postoperative resection status, and
      survival time. MRI might be a suitable technique for patient selection when
      considering peritonectomy and HIPEC. In our patients the outcome seems to
      correlate well with the extent of peritoneal carcinomatosis found by the
      preoperative MRI.

PMID- 24434840
TI  - An energy efficient compressed sensing framework for the compression of
      electroencephalogram signals.
AB  - The use of wireless body sensor networks is gaining popularity in monitoring and
      communicating information about a person's health. In such applications, the
      amount of data transmitted by the sensor node should be minimized. This is
      because the energy available in these battery powered sensors is limited. In this
      paper, we study the wireless transmission of electroencephalogram (EEG) signals.
      We propose the use of a compressed sensing (CS) framework to efficiently compress
      these signals at the sensor node. Our framework exploits both the temporal
      correlation within EEG signals and the spatial correlations amongst the EEG
      channels. We show that our framework is up to eight times more energy efficient
      than the typical wavelet compression method in terms of compression and encoding
      computations and wireless transmission. We also show that for a fixed compression
      ratio, our method achieves a better reconstruction quality than the CS-based
      state-of-the art method. We finally demonstrate that our method is robust to
      measurement noise and to packet loss and that it is applicable to a wide range of
      EEG signal types. 

PMID- 24434841
TI  - Autonomous oscillation of polymer chains induced by the Belousov-Zhabotinsky
      reaction.
AB  - We investigated the self-oscillating behaviors of two types of polymer chains
      induced by the Belousov-Zhabotinsky (BZ) reaction. One consisted of N
      isopropylacrylamide (NIPAAm) and the Ru catalyst of the BZ reaction, and the
      other consisted of NIPAAm, the Ru catalyst, and acrylamide-2
      methylpropanesulfonic acid (AMPS) with a negatively charged domain as a
      solubility control site. A comparison of the two types of self-oscillation
      systems showed that the anionic AMPS portion of the polymer chain significantly
      affected the self-oscillating behavior under strongly acidic condition. The
      periods of self-oscillation for the two types of self-oscillating polymer chains
      were investigated by changing the initial concentrations of the three BZ
      substrates and the temperature. As a result, it was demonstrated that the period
      of self-oscillation could be controlled by the concentration of the BZ substrates
      and the temperature. Furthermore, the activation energies of the two types of the
      self-oscillating polymer chains gave similar values as normal BZ reactions, i.e.,
      not including the self-oscillating polymer system with a Ru moiety. In addition,
      it was clarified the activation energy was hardly affected by the initial
      concentration of the three BZ substrates. 

PMID- 24434842
TI  - A strapdown interial navigation system/Beidou/Doppler velocity log integrated
      navigation algorithm based on a Cubature Kalman filter.
AB  - The integrated navigation system with strapdown inertial navigation system
      (SINS), Beidou (BD) receiver and Doppler velocity log (DVL) can be used in marine
      applications owing to the fact that the redundant and complementary information
      from different sensors can markedly improve the system accuracy. However, the
      existence of multisensor asynchrony will introduce errors into the system. In
      order to deal with the problem, conventionally the sampling interval is
      subdivided, which increases the computational complexity. In this paper, an
      innovative integrated navigation algorithm based on a Cubature Kalman filter
      (CKF) is proposed correspondingly. A nonlinear system model and observation model
      for the SINS/BD/DVL integrated system are established to more accurately describe
      the system. By taking multi-sensor asynchronization into account, a new sampling
      principle is proposed to make the best use of each sensor's information. Further,
      CKF is introduced in this new algorithm to enable the improvement of the
      filtering accuracy. The performance of this new algorithm has been examined
      through numerical simulations. The results have shown that the positional error
      can be effectively reduced with the new integrated navigation algorithm. Compared
      with the traditional algorithm based on EKF, the accuracy of the SINS/BD/DVL
      integrated navigation system is improved, making the proposed nonlinear
      integrated navigation algorithm feasible and efficient. 

PMID- 24434843
TI  - Hyperuricemia is a significant risk factor for the onset of chronic kidney
      disease.
AB  - BACKGROUND: Recent studies have shown that hyperuricemia is an independent risk
      factor for cardiovascular disease. However, few studies have examined whether
      hyperuricemia is a risk factor for chronic kidney disease (CKD), so to
      investigate the significance of hyperuricemia as a risk factor for CKD, we
      analyzed data collected in annual health check-ups. METHODS: The data of 11,048
      subjects who underwent an annual health check-up were analyzed in cross-sectional
      and longitudinal studies. RESULTS: After adjustment for covariate factors, a
      multivariate logistic regression analysis showed that age, systolic blood
      pressure, diastolic blood pressure, LDL-cholesterol, triglyceride, HbA1c, and
      uric acid (hazard ratio: 1.66) were independently and significantly associated
      with CKD. We also analyzed the data of 1,652 subjects who underwent annual health
      check-ups for 5 consecutive years. Over that 5-year period, 93 subjects developed
      CKD. We compared the baseline data of the subjects who developed CKD with the
      data of those who did not, and we found significant between-group differences in
      gender, age, HDL-cholesterol, the estimated glomerular filtration rate, and uric
      acid. After adjustment for several covariate factors, a multivariate Cox
      regression analysis showed that only age and hyperuricemia (hazard ratio: 1.36)
      were independent risk factors for the development of CKD. CONCLUSIONS: We found
      that hyperuricemia is an independent risk factor for the development of CKD.

PMID- 24434844
TI  - Medicinal plants of the genus Gelsemium (Gelsemiaceae, Gentianales)--a review of
      their phytochemistry, pharmacology, toxicology and traditional use.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the genus Gelsemium, Gelsemium elegans (Gardn.
      & Champ.) Benth. has been recognized as a toxic plant that is widely distributed
      in Southeast Asia and has been used as traditional Chinese medicine for the
      treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers and
      cancers for many years. Gelsemium sempervirens (L.) J.St.-Hil. has been used
      since the nineteenth century in homeopathy for treating anxiety, neuralgia,
      migraine and spasmodic disorders, such as asthma and whooping cough in North
      America. This review aims to provide comprehensive information on the botany,
      traditional uses, phytochemistry, pharmacological research and toxicology of
      medicinal plants in the genus Gelsemium. The overall objective is to explore the
      evidence supporting its ethnopharmacological effectiveness. MATERIALS AND
      METHODS: A literature survey was performed by searching the scientific databases
      Pubmed, Google Scholar, SciFinder, Scopus, Web of Science and the Chinese CNKI,
      in addition to traditional Chinese medicine and homeopathic texts for information
      on Gelsemium. RESULTS: Plants of the genus Gelsemium have been used in
      traditional medicine for the treatment of migraines, neuralgia, sciatica, cancer
      and various types of sores. Studies into the phytochemical composition of this
      genus have shown that all of the species are rich sources of monoterpene indole
      alkaloids and that they have attracted the attention of many researchers due to
      their markedly diverse and complex architecture. To date, a total of 121
      alkaloids have been isolated and identified from the genus. The crude extracts,
      as well as the monomeric compounds, from the genus possess anti-tumor, analgesic,
      anxiolytic, anti-inflammatory and immunomodulating pharmacological activities.
      CONCLUSION: It is evident from the available literature that Gelsemium species
      possess potential for use as a beneficial therapeutic remedy. However, the
      analysis of previous pharmacological research suggests that a clear assignment of
      active molecules and mechanisms of action is remain lacking. Due to their high
      toxicity, the studies available on toxicity and safety are inadequate for
      providing information on clinical utilization.

PMID- 24434846
TI  - Pluripotent stem cells in regenerative medicine: challenges and recent progress.
AB  - After years of incremental progress, several recent studies have succeeded in
      deriving disease-relevant cell types from human pluripotent stem cell (hPSC)
      sources. The prospect of an unlimited cell source, combined with promising
      preclinical data, indicates that hPSC technology may be on the verge of clinical
      translation. In this Review, we discuss recent progress in directed
      differentiation, some of the new technologies that have facilitated the success
      of hPSC therapies and the remaining hurdles on the road towards developing hPSC
      based cell therapies. 

PMID- 24434848
TI  - A network-based kernel machine test for the identification of risk pathways in
      genome-wide association studies.
AB  - Biological pathways provide rich information and biological context on the
      genetic causes of complex diseases. The logistic kernel machine test integrates
      prior knowledge on pathways in order to analyze data from genome-wide association
      studies (GWAS). In this study, the kernel converts the genomic information of 2
      individuals into a quantitative value reflecting their genetic similarity. With
      the selection of the kernel, one implicitly chooses a genetic effect model. Like
      many other pathway methods, none of the available kernels accounts for the
      topological structure of the pathway or gene-gene interaction types. However,
      evidence indicates that connectivity and neighborhood of genes are crucial in the
      context of GWAS, because genes associated with a disease often interact. Thus, we
      propose a novel kernel that incorporates the topology of pathways and information
      on interactions. Using simulation studies, we demonstrate that the proposed
      method maintains the type I error correctly and can be more effective in the
      identification of pathways associated with a disease than non-network-based
      methods. We apply our approach to genome-wide association case-control data on
      lung cancer and rheumatoid arthritis. We identify some promising new pathways
      associated with these diseases, which may improve our current understanding of
      the genetic mechanisms.

PMID- 24434849
TI  - Molecular detection of Lactobacillus species in the neovagina of male-to-female
      transsexual women.
AB  - There is a general opinion that penile skin lined neovagina of transsexual women
      is not able to support the growth of lactobacilli. This study was undertaken to
      prove if lactobacilli strains could survive in neovagina and to characterise the
      most dominant Lactobacillus species. Sixty three male-to-female transsexual women
      without abnormal vaginal discharge, clinical signs of infection were recruited on
      an ongoing basis from among transsexual outpatients in an academic research
      institution and tertiary care centre. Neovaginal smears were taken for molecular
      Lactobacillus spp. profiling by denaturing gradient gel electrophoresis (PCR
      DGGE). Lactobacillus species were detected from 47/63 transsexual women (75%).
      The 279 Lactobacillus signals detected by PCR-DGGE technique belonged to 13
      different species. Lactobacilli of the L. delbrueckii group (L. gasseri, L.
      crispatus, L. johnsonii, L. iners, L. jensenii) were predominant. More than 90%
      of women harboured a combination of two or more neovaginal Lactobacillus species.
      In this study we report the frequent occurrence of lactobacilli from neovagina of
      transsexual women. Both, frequency and composition were similar to the normal
      lactic acid bacterial microflora in both women of reproductive age and
      postmenopausal women. 

PMID- 24434850
TI  - Tunable colors and white-light emission based on a microporous luminescent Zn(II)
      MOF.
AB  - Metal-organic frameworks (MOFs) are a rapidly growing class of hybrid materials
      with many multifunctional properties. The permanent porosity plays a central role
      in the functional properties. In particular, the luminescent MOFs with a
      permanent porosity have wide applications in guest species recognition and
      adsorption. In this contribution, we aim to develop tunable colors and white
      light luminescence materials by the encapsulation of Ln(3+) species in
      microporous luminescent MOFs. A semi-rigid trivalent carboxylic acid 1,3,5-tri(4
      carboxyphenoxy)benzene (H3TCPB) was selected as the organic building block, not
      only because it is suitable to construct microporous frameworks, but also by
      reason of its blue luminescent emission. Under solvothermal reactions, a
      microporous MOF material, [Zn3(TCPB)2(H2O)2].2H2O.4DMF (JUC-113, JUC = Jilin
      University, China), was synthesized, which has a permanent porosity and emits
      blue light. According to three-primary colors, the guest luminescent species
      should be Tb(3+) and Eu(3+) owing to their distinctive colors (Tb(3+), green;
      Eu(3+), red). In addition, the luminescent properties of JUC-113 can be easily
      tuned by different combinations of the encapsulation amount of Tb(3+) and Eu(3+),
      obtaining white-light emission materials. 

PMID- 24434847
TI  - Sequencing depth and coverage: key considerations in genomic analyses.
AB  - Sequencing technologies have placed a wide range of genomic analyses within the
      capabilities of many laboratories. However, sequencing costs often set limits to
      the amount of sequences that can be generated and, consequently, the biological
      outcomes that can be achieved from an experimental design. In this Review, we
      discuss the issue of sequencing depth in the design of next-generation sequencing
      experiments. We review current guidelines and precedents on the issue of
      coverage, as well as their underlying considerations, for four major study
      designs, which include de novo genome sequencing, genome resequencing,
      transcriptome sequencing and genomic location analyses (for example, chromatin
      immunoprecipitation followed by sequencing (ChIP-seq) and chromosome conformation
      capture (3C)). 

PMID- 24434851
TI  - MBD4 cooperates with DNMT1 to mediate methyl-DNA repression and protects
      mammalian cells from oxidative stress.
AB  - Oxidative stress induces genome-wide remodeling of the chromatin structure. In
      this study, we identify Methyl-CpG Binding Protein 4 (MBD4), a multifunctional
      enzyme involved in DNA demethylation, base excision repair, and gene expression
      regulation, as an essential factor in response to oxidative stress. We provide
      evidence that MBD4 is upregulated at the protein level upon oxidative stress, and
      that MBD4 is essential for cell survival following oxidative stress. In these
      cells, MBD4 and DNMT1 are recruited at sites of oxidation-induced DNA damage,
      where we speculate they participate in DNA repair. MBD4 and DNMT1 also share
      genomic targets in unstressed cells. Using genome-wide analysis of MBD4 binding
      sites, we identified new targets potentially co-regulated by MBD4 and DNA
      methylation. We identified two new binding sites for MBD4 and DNMT1 at methylated
      CpG islands of CDKN1A/p21 and MSH4, where they synergistically mediate
      transcriptional repression. Our study provides evidence that the interaction
      between DNMT1 and MBD4 is involved in controlling gene expression and responding
      to oxidative stress. 

PMID- 24434852
TI  - Improvement of energy expenditure prediction from heart rate during running.
AB  - We aimed to develop new equations that predict exercise-induced energy
      expenditure (EE) more accurately than previous ones during running by including
      new parameters as fitness level, body composition and/or running intensity in
      addition to heart rate (HR). Original equations predicting EE were created from
      data obtained during three running intensities (25%, 50% and 70% of HR reserve)
      performed by 50 subjects. Five equations were conserved according to their
      accuracy assessed from error rates, interchangeability and correlations analyses:
      one containing only basic parameters, two containing VO2max or speed at VO2max
      and two including running speed with or without HR. Equations accuracy was
      further tested in an independent sample during a 40 min validation test at 50% of
      HR reserve. It appeared that: (1) the new basic equation was more accurate than
      pre-existing equations (R(2) 0.809 versus. 0,737 respectively); (2) the
      prediction of EE was more accurate with the addition of VO2max (R(2) = 0.879);
      and (3) the equations containing running speed were the most accurate and were
      considered to have good agreement with indirect calorimetry. In conclusion, EE
      estimation during running might be significantly improved by including running
      speed in the predictive models, a parameter readily available with treadmill or
      GPS. 

PMID- 24434853
TI  - Is there a relationship between right-ventricular and right atrial mechanics and
      functional capacity in hypertensive patients?
AB  - BACKGROUND: We sought to assess right-ventricular and right atrial deformation in
      patients with arterial hypertension by two-dimensional speckle tracking imaging
      and three-dimensional echocardiography (3DE), and define the relationship between
      right-ventricular mechanics and exercise capacity in the study population.
      METHODS: This cross-sectional study included recently diagnosed untreated
      hypertensive patients, well controlled hypertensive patients, treated patients
      with unsatisfactory controlled blood pressure and control individuals adjusted by
      sex and age. All the patients underwent complete two-dimensional echocardiography
      and 3DE examination, as well as cardiopulmonary exercise testing. RESULTS: Right
      ventricular strain, and systolic and early diastolic strain rates were
      significantly decreased in the untreated and the uncontrolled hypertensive
      patients in comparison with the controls and the well controlled participants.
      Similar results were obtained for right atrial strain and strain rates. 3DE right
      ventricular volumes were increased, whereas 3DE right-ventricular ejection
      fraction was decreased in the uncontrolled hypertensive patients in comparison
      with the controls and the well treated patients. Differences in 3DE right
      ventricular volumes disappeared after adjustment for body surface area.
      Considering the whole study population, global right-ventricular strain (beta =
      0.29, P = 0.018) and 3D right-ventricular stroke volume (beta = 0.22, P = 0.041)
      were independently associated with peak oxygen uptake (VO(2max)) which was
      significantly decreased in the untreated and the uncontrolled hypertensive
      patients in comparison with the remaining two groups. CONCLUSION: Our study
      showed that right-ventricular and right atrial mechanics, as well as exercise
      capacity, are significantly deteriorated in the hypertensive patients who are
      untreated or ineffectively treated. Global right-ventricular strain and 3DE right
      ventricular stroke volume are independently associated with functional capacity
      in the whole study population.

PMID- 24434854
TI  - Pre-end-stage renal disease care not associated with dialysis facility
      neighborhood poverty in the United States.
AB  - BACKGROUND: Receipt of nephrology care prior to end-stage renal disease (ESRD) is
      a strong predictor of decreased mortality and morbidity, and neighborhood poverty
      may influence access to care. Our objective was to examine whether neighborhood
      poverty is associated with lack of pre-ESRD care at dialysis facilities. METHODS:
      In a multi-level ecological study using geospatially linked 2007-2010 Dialysis
      Facility Report and 2006-2010 American Community Survey data, we examined whether
      high neighborhood poverty (>=20% of households in census tract living below
      poverty) was associated with dialysis facility-level lack of pre-ESRD care
      (percentage of patients with no nephrology care prior to dialysis start) in mixed
      effects models, adjusting for facility and neighborhood confounders and allowing
      for neighborhood and regional random effects. RESULTS: Among the 5,184 facilities
      examined, 1,778 (34.3%) were located in a high-poverty area. Lack of pre-ESRD
      care was similar in poverty areas (30.8%) and other neighborhoods (29.6%). With
      adjustment, the absolute increase in percentage of patients at a facility with no
      pre-ESRD care associated with facility location in a poverty area versus other
      neighborhood was only 0.08% (95% CI -1.32, 1.47; p = 0.9). Potential effect
      modification by race and income inequality was detected. CONCLUSION: Despite
      previously reported detrimental effects of neighborhood poverty on health,
      facility neighborhood poverty was not associated with receipt of pre-ESRD care,
      suggesting no need to target interventions to increase access to pre-ESRD care at
      facilities in poorer geographic areas.

PMID- 24434856
TI  - Clinical engagement: improving healthcare together.
AB  - Clinical engagement can achieve lasting change in the delivery of healthcare. In
      October 2011, Healthcare Improvement Scotland formulated a clinical engagement
      strategy to ensure that a progressive and sustainable approach to engaging
      healthcare professionals is firmly embedded in its health improvement and public
      assurance activities. The strategy was developed using a 90-day process,
      combining an evidence base of best practice and feedback from semi-structured
      interviews and focus groups. The strategy aims to create a culture where
      clinicians view working with Healthcare Improvement Scotland as a worthwhile
      venture, which offers a number of positive benefits such as training, career
      development and research opportunities. The strategy works towards developing a
      respectful partnership between Healthcare Improvement Scotland, the clinical
      community and key stakeholders whereby clinicians' contributions are recognised
      in a non-financial reward system. To do this, the organisation needs a
      sustainable infrastructure and an efficient, cost-effective approach to clinical
      engagement. There are a number of obstacles to achieving successful clinical
      engagement and these must be addressed as key drivers in its implementation. The
      implementation of the strategy is supported by an action and resource plan, and
      its impact will be monitored by a measurement plan to ensure the organisation
      reviews its approaches towards clinical engagement. 

PMID- 24434855
TI  - The genetics of cognitive epigenetics.
AB  - Cognitive disorders (CDs) are a heterogeneous group of disorders for which the
      genetic foundations are rapidly being uncovered. The large number of CD
      associated gene mutations presents an opportunity to identify common mechanisms
      of disease as well as molecular processes that are of key importance to human
      cognition. Given the disproportionately high number of epigenetic genes
      associated with CD, epigenetic regulation of gene transcription is emerging as a
      process of major importance in cognition. The cognate protein products of these
      genes often co-operate in shared protein complexes or pathways, which is
      reflected in similarities between the neurodevelopmental phenotypes corresponding
      to these mutant genes. Here we provide an overview of the genes associated with
      CDs, and highlight some of the epigenetic regulatory complexes involving multiple
      CD genes. Such common gene networks may provide a handle for designing
      therapeutic interventions applicable to a number of cognitive disorders with
      variable genetic etiology.

PMID- 24434857
TI  - A national survey of attitudes to research in Scottish General Surgery Trainees.
AB  - INTRODUCTION: Given the importance placed on awareness and participation in
      research by Speciality and Training organisations, we sought to survey Scottish
      trainee attitudes to exposure to research practice during training and research
      in or out of programme. METHODS: An online survey was distributed to core and
      specialist trainees in general surgery in Scotland. RESULTS: Over a 4-month
      period, 108 trainees (75 ST/SPRs and 33 CTs) completed the survey. In their
      current post, most were aware of ongoing research projects (77%) and 55% were
      aware of trial recruitment. Only 47% attend regular journal clubs. Most believe
      that they are expected to present (89%) and publish (82%) during training. Most
      (59%) thought that participation in research is well supported. 57% were advised
      to undertake time out of programme research, mostly by consultants (48%) and
      training committee (36%). Of the 57 with time out of programme research
      experience, most did so in early training (37%) or between ST3-5 (47%). 28 out of
      the 36 (78%) without a national training number secured one after starting
      research. Most undertook research in a local academic unit (80%) funded by small
      grants (47%) or internally (33%). Most research (69%) was clinically orientated
      (13/55 clinical, 25/55 translational). 56% of those completing time out of
      programme research obtained an MD or PhD. About 91% thought that research was
      relevant to a surgical career. CONCLUSIONS: Most trainees believe that research
      is an important part of training. Generally, most trainees are exposed to
      research practices including trial recruitment. However, <50% attend regular
      journal clubs, a pertinent point, given the current 'exit exam' includes the
      assessment of critical appraisal skills.

PMID- 24434858
TI  - A carcinoid tumour arising within a tailgut cyst: a diagnostic challenge.
AB  - A 49-year-old man was referred with constipation that had lasted for a few
      months. On colonoscopy, a subepithelial tumour more than 4 cm in size was seen in
      the rectum. He underwent endoscopic ultrasound and pelvic magnetic resonance
      imaging. He was preoperatively diagnosed with a rectal duplication cyst based on
      imaging studies. However, the final histopathologic diagnosis after transanal
      excision of the rectal mass was rectal carcinoid tumour with tailgut cyst.
      Tailgut cysts are very rare congenital lesions in the presacral area and are most
      often discovered incidentally in middle-aged women. It is difficult to
      distinguish the imaging appearance of tailgut cysts from that of many other
      retrorectal cysts. Malignant transformation of tailgut cysts has been estimated
      to occur in 2 to 13% of cases. We report the diagnostic difficulties encountered
      in a case of carcinoid tumour arising from a tailgut cyst in a male patient. 

PMID- 24434859
TI  - Measles in Scotland, 2013.
AB  - In 2013, Wales and England experienced large outbreaks of measles, a disease that
      has been targeted by the World Health Organisation for European elimination by
      2015. Unfortunately, measles-mumps-rubella vaccine uptake declined to less than
      80% in Wales and England after the Wakefield publicity and this resulted in
      increased population susceptibility to measles. In Scotland, measles-mumps
      rubella vaccine uptake dropped to 87% in 2003. Scottish public health efforts in
      response to this decline aimed to maximise uptake of MMR1 by two years; ensure at
      least 95% uptake of one dose of measles-mumps-rubella before starting school at
      age five; and maximise uptake of the second dose of measles-mumps-rubella by age
      six. Although Scotland has not had any large outbreaks reported to date,
      transmission of measles from healthcare workers to patients has occurred and
      reiterates the importance of all healthcare workers accurately knowing their
      immune status and, when needed, to be fully immunised. 

PMID- 24434860
TI  - Light responsive thin films of micelles of PS-b-PVP complexed with diazophenol
      chromophore.
AB  - We have incorporated push-pull azobenzene units into diblock-copolymer micelles
      by supramolecular assembly. Specifically, we encapsulated a phenol-functionalized
      chromophore, DO13, within PS-b-P4VP micelles in toluene by means of H-bond
      interactions developed between DO13 molecules and pyridine groups of P4VP block.
      The solutions were spin-coated onto glass substrates resulting in multi- or mono
      layered thin films of micelles with P4VP(DO13) core and PS corona. We show that
      the use of DO13 as a building block of micellar aggregates allowed us to
      manipulate the developed nanostructures. Spherical to cylindrical micellar
      transition was found when we increased the degree of chromophore complexation.
      Also, it was found that the polymer concentration in the solution plays an
      important role in determining the micellar nanostructures. The chain extension
      and change in composition of the P4VP core in the presence of the chromophore may
      be responsible for the structural changes observed in the micelles. The optical
      properties of the thin films have been investigated focusing on the effect of the
      micellar morphology over the photoinduced birefringence. The optical anisotropy
      (Deltan) increased with respect to the analogous homogeneous system P4VP(DO13),
      indicating that the protective micelle environment can enhance the optical
      properties of the embedded chromophores significantly. Furthermore, we show very
      interesting new results in which we have related changes in optical properties to
      the film morphology (spheres to cylinders). This can be exploited for producing
      optical devices having improved optoelectronic properties and stability.

PMID- 24434861
TI  - Focal resection of leptomeningeal angioma in a rare case of Sturge-Weber syndrome
      without facial nevus.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous disorder comprised typically of a
      facial nevus, leptomeningeal angioma with calcifications, and seizures. SWS
      without a port-wine stain is a rare variant with only 30 cases reported in the
      literature. Here, a case of an 8-year-old girl with no cutaneous abnormalities
      presenting with medically intractable epilepsy and MRI and CT findings consistent
      with SWS is described. The patient underwent multistage surgery with subdural
      electrode monitoring before and after resection of the epileptogenic focus, with
      complete excision of the lesion and postoperative resolution of her seizures.
      This is the first reported case of three-stage surgery for localized resection of
      the seizure focus for SWS.

PMID- 24434862
TI  - Philadelphia chromosome-negative very high-risk acute lymphoblastic leukemia in
      children and adolescents: results from Children's Oncology Group Study AALL0031.

PMID- 24434863
TI  - A common alternative splicing signature is associated with SF3B1 mutations in
      malignancies from different cell lineages.

PMID- 24434864
TI  - On rare-variant analysis in population-based designs: decomposing the likelihood
      to two informative components.
AB  - Various analytical approaches have been suggested for the characterization of
      rare variants. One main approach is to collapse the genetic information of rare
      variants in a region and to construct an overall test statistic. Here, we
      proposed a new approach based on collapsed genotype scores. By utilizing the
      information of the association signal that is ignored in collapsing methods, i.e.
      the configuration of rare alleles, we constructed a more powerful test and
      compared it with existing rare-variant approaches. With extensive simulation
      studies, we showed that our method performs better than existing approaches, and
      we applied our method to a sequencing study of nonsyndromic cleft lip
      illustrating the practical advantages of the proposed method.

PMID- 24434865
TI  - Effect of different immunosuppressive drugs on immune cells from young and old
      healthy persons.
AB  - BACKGROUND: Life expectancy, as well as the average age of patients undergoing
      solid organ transplantation, increases constantly. Consequently,
      immunosuppressive therapy is no longer limited to young organ recipients.
      OBJECTIVE: Here, we investigate how different types of immunosuppressive therapy,
      namely the calcineurin inhibitors cyclosporin A and tacrolimus, as well as the
      mTOR inhibitor rapamycin, affect the function of immune cells in young and
      elderly persons. METHODS: Proliferation, cell viability, cytokine production (IL
      2, IFN-gamma), H2O2 production and telomere length of phytohemagglutinin (PHA)
      stimulated human peripheral blood mononuclear cells (PBMCs) of young (n = 13;
      median age 27 years) and old (n = 19; median age 71 years) healthy donors were
      analyzed. RESULTS: The inhibition of proliferation was dampened in PBMCs from
      elderly donors, especially after incubation with rapamycin. All three
      immunosuppressive drugs inhibited the production of IL-2 equally well, whereas
      the production of IFN-gamma was less well inhibited by rapamycin. Both
      calcineurin inhibitors increased H2O2 concentrations after stimulation with PHA
      and led to a shortening of telomeres in PBMCs from young and old individuals.
      Rapamycin had only minor effects on H2O2 production and telomere length.
      CONCLUSION: Our results demonstrate that the effects of immunosuppressive drugs
      on PBMCs differ between young and elderly persons. Calcineurin inhibitors
      compared to rapamycin have a more pronounced prosenescence effect. These data
      indicate that specific treatment regimens for the elderly might therefore be
      considered.

PMID- 24434866
TI  - Epitaxial graphene on SiC{0001}: advances and perspectives.
AB  - We review here recent progress on epitaxial graphene grown on a SiC substrate.
      Epitaxial graphene can be easily grown by heating the SiC single crystal in a
      high vacuum or in an inert gas atmosphere. The SiC surfaces used for graphene
      growth contain Si- and C-terminated faces. On the Si-face, homogeneous and clean
      graphene can be grown with a controlled number of layers, and the carrier
      mobility reaches as high as several m(2) V s(-1), although this is reduced by the
      presence of the substrate steps. On the C-face, although the number of layers is
      not homogeneous, twisted bilayer graphene can be grown, which is expected to be
      the technique of choice to modify the electronic structure of graphene. From the
      application point of view, graphene on SiC will be the platform used to fabricate
      high-speed electronic devices and dense graphene nanoribbon arrays, which will be
      used to introduce a bandgap. 

PMID- 24434867
TI  - Bacteriophages: biosensing tools for multi-drug resistant pathogens.
AB  - Pathogen detection is of utmost importance in many sectors, such as in the food
      industry, environmental quality control, clinical diagnostics, bio-defence and
      counter-terrorism. Failure to appropriately, and specifically, detect pathogenic
      bacteria can lead to serious consequences, and may ultimately be lethal. Public
      safety, new legislation, recent outbreaks in food contamination, and the ever
      increasing prevalence of multidrug-resistant infections have fostered a worldwide
      research effort targeting novel biosensing strategies. This review concerns phage
      based analytical and biosensing methods targeted towards theranostic
      applications. We discuss and review phage-based assays, notably phage
      amplification, reporter phage, phage lysis, and bioluminescence assays for the
      detection of bacterial species, as well as phage-based biosensors, including
      optical (comprising SPR sensors and fiber optic assays), electrochemical
      (comprising amperometric, potentiometric, and impedimetric sensors), acoustic
      wave and magnetoelastic sensors. 

PMID- 24434868
TI  - Elective caesarean section is associated with low adiponectin levels in cord
      blood.
AB  - BACKGROUND: Caesarean section rates have increased in parallel with those of
      obesity. Decreased levels of adiponectin, an adipocyte-derived metabolic hormone
      present in abundant concentrations in cord blood and breast milk, have been
      documented in association with obesity in children and adults. OBJECTIVE: To
      determine whether the mode of delivery affects adiponectin concentrations in cord
      blood of healthy term infants. METHODS: The cord blood adiponectin concentration
      was measured in 159 consecutive term infants, of whom 131 (82.4%) were born by
      vaginal delivery, 15 (9.4%) by nonelective caesarean section and 13 (8.2%) by
      elective caesarean section. RESULTS: The mean adiponectin level was significantly
      lower in infants born by elective caesarean section compared with those born by
      vaginal delivery: 15.3 ug/ml (SD = 6.8) and 21.6 ug/ml (SD = 7.3), respectively
      (p = 0.015). This difference remained significant after adjustment for the
      infants' gender and birth weight as well as maternal weight and weight gain
      during pregnancy. CONCLUSION: Elective caesarean section may carry a risk of
      obesity independently of maternal risk factors.

PMID- 24434869
TI  - Animal model of methylphenidate's long-term memory-enhancing effects.
AB  - Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds
      of current prescriptions for attention deficit hyperactivity disorder (ADHD).
      Although many studies have modeled MPH's effect on executive function, almost
      none have directly modeled its effect on long-term memory (LTM), even though
      improvement in LTM is a critical target of therapeutic intervention in ADHD. We
      examined the effects of a wide range of doses of MPH (0.01-10 mg/kg, i.p.) on
      Pavlovian fear learning, a leading model of memory. MPH's effects were then
      compared to those of atomoxetine (0.1-10 mg/kg, i.p.), bupropion (0.5-20 mg/kg,
      i.p.), and citalopram (0.01-10 mg/kg, i.p.). At low, clinically relevant doses,
      MPH enhanced fear memory; at high doses it impaired memory. MPH's memory
      enhancing effects were not confounded by its effects on locomotion or anxiety.
      Further, MPH-induced memory enhancement seemed to require both dopamine and
      norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1
      mg/kg and 10 mg/kg) was compared to those of two other psychostimulants,
      amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg),
      using a conditioned place preference and behavioral sensitization paradigm. We
      found that memory-enhancing effects of psychostimulants observed at low doses are
      readily dissociable from their reinforcing and locomotor activating effects at
      high doses. Together, our data suggest that fear conditioning will be an
      especially fruitful platform for modeling the effects of psychostimulants on LTM
      in drug development. 

PMID- 24434870
TI  - A novel role for the rat retrosplenial cortex in cognitive control.
AB  - By virtue of its frontal and hippocampal connections, the retrosplenial cortex is
      uniquely placed to support cognition. Here, we tested whether the retrosplenial
      cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the
      ability to select between conflicting responses and inhibit responding to task
      irrelevant cues. Rats first acquired two instrumental conditional
      discriminations, one auditory and one visual, set in two distinct contexts. As a
      result, rats were rewarded for pressing either the right or left lever when a
      particular auditory or visual signal was present. In extinction, rats received
      compound stimuli that either comprised the auditory and visual elements that
      signaled the same lever response (congruent) or signaled different lever
      responses (incongruent) during training. On conflict (incongruent) trials, lever
      selection by sham-operated animals followed the stimulus element that had
      previously been trained in that same test context, whereas animals with
      retrosplenial cortex lesions failed to disambiguate the conflicting response
      cues. Subsequent experiments demonstrated that this abnormality on conflict
      trials was not due to a failure in distinguishing the contexts. Rather, these
      data reveal the selective involvement of the rat retrosplenial cortex in response
      conflict, and so extend the frontal system underlying cognitive control.

PMID- 24434871
TI  - Activity-dependent changes in MAPK activation in the Angelman Syndrome mouse
      model.
AB  - Angelman Syndrome (AS) is a devastating neurological disorder caused by
      disruption of the maternal UBE3A gene. Ube3a protein is identified as an E3
      ubiquitin ligase that shows neuron-specific imprinting. Despite extensive
      research evaluating the localization and basal expression profiles of Ube3a in
      mouse models, the molecular mechanisms whereby Ube3a deficiency results in AS are
      enigmatic. Using in vitro and in vivo systems we show dramatic changes in the
      expression of Ube3a following synaptic activation. In primary neuronal culture,
      neuronal depolarization was found to increase both nuclear and cytoplasmic Ube3a
      levels. Analogous up-regulation in maternal and paternal Ube3a expression was
      observed in Ube3a-YFP reporter mice following fear conditioning. Absence of Ube3a
      led to deficits in the activity-dependent increases in ERK1/2 phosphorylation,
      which may contribute to reported deficits in synaptic plasticity and cognitive
      function in AS mice. Taken together, our findings provide novel insight into the
      regulation of Ube3a by synaptic activity and its potential role in kinase
      regulation.

PMID- 24434872
TI  - On the ergodicity of supercooled molecular glass-forming liquids at the dynamical
      arrest: the o-terphenyl case.
AB  - The dynamics of supercooled ortho-terphenyl has been studied using photon
      correlation spectroscopy (PCS) in the depolarized scattering geometry. The
      obtained relaxation curves are analyzed according to the mode-coupling theory
      (MCT) for supercooled liquids. The main results are: i) the observation of the
      secondary Johari-Goldstein relaxation (beta) that has its onset just at the
      dynamical crossover temperature TB (TM > TB > Tg); ii) the confirmation, of the
      suggestion of a recent statistical mechanical study, that such a molecular system
      remains ergodic also below the calorimetric glass-transition temperature Tg. Our
      experimental data give evidence that the time scales of the primary (alpha) and
      this secondary relaxations are correlated. Finally a comparison with recent PCS
      experiments in a colloidal system confirms the primary role of the dynamical
      crossover in the physics of the dynamical arrest. 

PMID- 24434873
TI  - A non-intrusive method for monitoring the degradation of MOSFETs.
AB  - Highly reliable embedded systems have been widely applied in the fields of
      aerospace, nuclear power, high-speed rail, etc., which are related to security
      and economic development. The reliability of the power supply directly influences
      the security of the embedded system, and has been the research focus of numerous
      electronic information and energy studies. The degradation of power modules
      occupies a dominant position among the key factors affecting the power supply
      reliability. How to dynamically determine the degradation state and forecast the
      remaining useful life of working power modules is critical. Therefore, an online
      non-intrusive method of obtaining the degradation state of MOSFETs based on the
      Volterra series is proposed. It uses the self-driving signal of MOSFETs as a non
      intrusive incentive, and extracts the degradation characteristics of MOSFETs by
      the frequency-domain kernel of the Volterra series. Experimental results show
      that the identification achieved by the method agrees well with the theoretical
      analysis. 

PMID- 24434874
TI  - Optimization of ERK activity biosensors for both ratiometric and lifetime FRET
      measurements.
AB  - Among biosensors, genetically-encoded FRET-based biosensors are widely used to
      localize and measure enzymatic activities. Kinases activities are of particular
      interest as their spatiotemporal regulation has become crucial for the deep
      understanding of cell fate decisions. This is especially the case for ERK, whose
      activity is a key node in signal transduction pathways and can direct the cell
      into various processes. There is a constant need for better tools to analyze
      kinases in vivo, and to detect even the slightest variations of their activities.
      Here we report the optimization of the previous ERK activity reporters, EKAR and
      EKAREV. Those tools are constituted by two fluorophores adapted for FRET
      experiments, which are flanking a specific substrate of ERK, and a domain able to
      recognize and bind this substrate when phosphorylated. The latter phosphorylation
      allows a conformational change of the biosensor and thus a FRET signal. We
      improved those biosensors with modifications of: (i) fluorophores and (ii)
      linkers between substrate and binding domain, resulting in new versions that
      exhibit broader dynamic ranges upon EGF stimulation when FRET experiments are
      carried out by fluorescence lifetime and ratiometric measurements. Herein, we
      characterize those new biosensors and discuss their observed differences that
      depend on their fluorescence properties. 

PMID- 24434875
TI  - A methodology to assess the accuracy with which remote data characterize a
      specific surface, as a function of Full Width at Half Maximum (FWHM): application
      to three Italian coastal waters.
AB  - This methodology assesses the accuracy with which remote data characterizes a
      surface, as a function of Full Width at Half Maximum (FWHM). The purpose is to
      identify the best remote data that improves the characterization of a surface,
      evaluating the number of bands in the spectral range. The first step creates an
      accurate dataset of remote simulated data, using in situ hyperspectral
      reflectances. The second step evaluates the capability of remote simulated data
      to characterize this surface. The spectral similarity measurements, which are
      obtained using classifiers, provide this capability. The third step examines the
      precision of this capability. The assumption is that in situ hyperspectral
      reflectances are considered the "real" reflectances. They are resized with the
      same spectral range of the remote data. The spectral similarity measurements
      which are obtained from "real" resized reflectances, are considered "real"
      measurements. Therefore, the quantity and magnitude of "errors" (i.e.,
      differences between spectral similarity measurements obtained from "real" resized
      reflectances and from remote data) provide the accuracy as a function of FWHM.
      This methodology was applied to evaluate the accuracy with which CHRIS-mode1,
      CHRIS-mode2, Landsat5-TM, MIVIS and PRISMA data characterize three coastal
      waters. Their mean values of uncertainty are 1.59%, 3.79%, 7.75%, 3.15% and
      1.18%, respectively. 

PMID- 24434876
TI  - Biosensing using microring resonator interferograms.
AB  - Optical low-coherence interferometry (OLCI) takes advantage of the variation in
      refractive index in silicon-wire microring resonator (MRR) effective lengths to
      perform glucose biosensing using MRR interferograms. The MRR quality factor (Q),
      proportional to the effective length, could be improved using the silicon-wire
      propagation loss and coupling ratio from the MRR coupler. Our study showed that
      multimode interference (MMI) performed well in broad band response, but the
      splitting ratio drifted to 75/25 due to the stress issue. The glucose sensing
      sensitivity demonstrated 0.00279 meter per refractive-index-unit (RIU) with a Q
      factor of ~30,000 under transverse electric polarization. The 1,310 nm DFB laser
      was built in the OLCI system as the optical ruler achieving 655 nm
      characterization accuracy. The lowest sensing limitation was therefore 2 * 10-4
      RIU. Moreover, the MRR effective length from the glucose sensitivity could be
      utilized to experimentally demonstrate the silicon wire effective refractive
      index with a width of 0.45 mm and height of 0.26 mm. 

PMID- 24434878
TI  - An experimental study on the effect of temperature on piezoelectric sensors for
      impedance-based structural health monitoring.
AB  - The electromechanical impedance (EMI) technique is considered to be one of the
      most promising methods for developing structural health monitoring (SHM) systems.
      This technique is simple to implement and uses small and inexpensive
      piezoelectric sensors. However, practical problems have hindered its application
      to real-world structures, and temperature effects have been cited in the
      literature as critical problems. In this paper, we present an experimental study
      of the effect of temperature on the electrical impedance of the piezoelectric
      sensors used in the EMI technique. We used 5H PZT (lead zirconate titanate)
      ceramic sensors, which are commonly used in the EMI technique. The experimental
      results showed that the temperature effects were strongly frequency-dependent,
      which may motivate future research in the SHM field. 

PMID- 24434877
TI  - Topoisomerase I as a biomarker: detection of activity at the single molecule
      level.
AB  - Human topoisomerase I (hTopI) is an essential cellular enzyme. The enzyme is
      often upregulated in cancer cells, and it is a target for chemotherapeutic drugs
      of the camptothecin (CPT) family. Response to CPT-based treatment is dependent on
      hTopI activity, and reduction in activity, and mutations in hTopI have been
      reported to result in CPT resistance. Therefore, hTOPI gene copy number, mRNA
      level, protein amount, and enzyme activity have been studied to explain
      differences in cellular response to CPT. We show that Rolling Circle Enhanced
      Enzyme Activity Detection (REEAD), allowing measurement of hTopI cleavage
      religation activity at the single molecule level, may be used to detect
      posttranslational enzymatic differences influencing CPT response. These
      differences cannot be detected by analysis of hTopI gene copy number, mRNA
      amount, or protein amount, and only become apparent upon measuring the activity
      of hTopI in the presence of CPT. Furthermore, we detected differences in the
      activity of the repair enzyme tyrosyl-DNA phosphodiesterase 1, which is involved
      in repair of hTopI-induced DNA damage. Since increased TDP1 activity can reduce
      cellular CPT sensitivity we suggest that a combined measurement of TDP1 activity
      and hTopI activity in presence of CPT will be the best determinant for CPT
      response. 

PMID- 24434879
TI  - Possibilities of a personal laser scanning system for forest mapping and
      ecosystem services.
AB  - A professional-quality, personal laser scanning (PLS) system for collecting tree
      attributes was demonstrated in this paper. The applied system, which is wearable
      by human operators, consists of a multi-constellation navigation system and an
      ultra-high-speed phase-shift laser scanner mounted on a rigid baseplate and
      consisting of a single sensor block. A multipass-corridor-mapping method was
      developed to process PLS data and a 2,000 m2 forest plot was utilized in the
      test. The tree stem detection accuracy was 82.6%; the root mean square error
      (RMSE) of the estimates of tree diameter at breast height (DBH) was 5.06 cm; the
      RMSE of the estimates of tree location was 0.38 m. The relative RMSE of the DBH
      estimates was 14.63%. The results showed, for the first time, the potential of
      the PLS system in mapping large forest plots. Further research on mapping
      accuracy in various forest conditions, data correction methods and multi-sensoral
      positioning techniques is needed. The utilization of this system in different
      applications, such as harvester operations, should also be explored. In addition
      to collecting tree-level and plot-level data for forest inventory, other possible
      applications of PLS for forest ecosystem services include mapping of canopy gaps,
      measuring leaf area index of large areas, documenting and visualizing forest
      routes feasible for recreation, hiking and berry and mushroom picking. 

PMID- 24434880
TI  - Adjustment of measurements with multiplicative errors: error analysis, estimates
      of the variance of unit weight, and effect on volume estimation from LiDAR-type
      digital elevation models.
AB  - Modern observation technology has verified that measurement errors can be
      proportional to the true values of measurements such as GPS, VLBI baselines and
      LiDAR. Observational models of this type are called multiplicative error models.
      This paper is to extend the work of Xu and Shimada published in 2000 on
      multiplicative error models to analytical error analysis of quantities of
      practical interest and estimates of the variance of unit weight. We analytically
      derive the variance-covariance matrices of the three least squares (LS)
      adjustments, the adjusted measurements and the corrections of measurements in
      multiplicative error models. For quality evaluation, we construct five estimators
      for the variance of unit weight in association of the three LS adjustment
      methods. Although LiDAR measurements are contaminated with multiplicative random
      errors, LiDAR-based digital elevation models (DEM) have been constructed as if
      they were of additive random errors. We will simulate a model landslide, which is
      assumed to be surveyed with LiDAR, and investigate the effect of LiDAR-type
      multiplicative error measurements on DEM construction and its effect on the
      estimate of landslide mass volume from the constructed DEM. 

PMID- 24434881
TI  - Recommendations for standardizing validation procedures assessing physical
      activity of older persons by monitoring body postures and movements.
AB  - Physical activity is an important determinant of health and well-being in older
      persons and contributes to their social participation and quality of life. Hence,
      assessment tools are needed to study this physical activity in free-living
      conditions. Wearable motion sensing technology is used to assess physical
      activity. However, there is a lack of harmonisation of validation protocols and
      applied statistics, which make it hard to compare available and future studies.
      Therefore, the aim of this paper is to formulate recommendations for assessing
      the validity of sensor-based activity monitoring in older persons with focus on
      the measurement of body postures and movements. Validation studies of body-worn
      devices providing parameters on body postures and movements were identified and
      summarized and an extensive inter-active process between authors resulted in
      recommendations about: information on the assessed persons, the technical system,
      and the analysis of relevant parameters of physical activity, based on a
      standardized and semi-structured protocol. The recommended protocols can be
      regarded as a first attempt to standardize validity studies in the area of
      monitoring physical activity. 

PMID- 24434882
TI  - Development: morphogen gradients revisited.

PMID- 24434883
TI  - DNA damage response: a ligase makes sense of DNA damage.

PMID- 24434885
TI  - The lipid trade.

PMID- 24434886
TI  - Zolpidem and restoration of consciousness.
AB  - OBJECTIVE: Zolpidem has been reported to cause temporary recovery of
      consciousness in vegetative and minimally conscious patients, but how often and
      why this occurs are unknown. The authors aimed to determine the frequency of this
      phenomenon and whether it can be predicted from demographic and clinical
      variables. DESIGN: This is a placebo-controlled, double-blind, single-dose,
      crossover study performed by caregivers and replicated by trained professionals,
      for naive participants. Four previously identified responders were also studied
      to further characterize the clinical drug response. RESULTS: Eighty-four
      participants with traumatic and nontraumatic disorders of consciousness of at
      least 4 mos' duration were studied. Four "definite responders" were identified,
      but no demographic or clinical features were predictive of the response.
      Indicators of a drug response included increased movement, social interaction,
      command following, attempts at communication, and functional object use;
      typically lasted 1-2 hrs; and sometimes ended with increased somnolence. Adverse
      events were more common on zolpidem than placebo, but most were rated as mild.
      CONCLUSIONS: Approximately 5% (4.8%) of the participants responded to zolpidem,
      but the responders could not be distinguished in advance from the nonresponders.
      Future research is needed to understand the mechanism of zolpidem in enhancing
      consciousness and its potential role in treatment and research.

PMID- 24434884
TI  - Synthetic biology in mammalian cells: next generation research tools and
      therapeutics.
AB  - Recent progress in DNA manipulation and gene circuit engineering has greatly
      improved our ability to programme and probe mammalian cell behaviour. These
      advances have led to a new generation of synthetic biology research tools and
      potential therapeutic applications. Programmable DNA-binding domains and RNA
      regulators are leading to unprecedented control of gene expression and
      elucidation of gene function. Rebuilding complex biological circuits such as T
      cell receptor signalling in isolation from their natural context has deepened our
      understanding of network motifs and signalling pathways. Synthetic biology is
      also leading to innovative therapeutic interventions based on cell-based
      therapies, protein drugs, vaccines and gene therapies. 

PMID- 24434887
TI  - Effect of whole-body vibration on muscle strength and balance in diplegic
      cerebral palsy: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of whole-body
      vibration training on muscle strength and balance in children with diplegic
      cerebral palsy. DESIGN: Fifteen children were assigned to the experimental group,
      which received whole-body vibration training (9 mins per day, 5 days per week).
      Another 15 were assigned to the control group, which participated in a
      traditional physical therapy exercise program for 3 successive months. Baseline
      and posttreatment assessments were performed using the Biodex isokinetic
      dynamometer to evaluate the knee extensors peak torque at 60 degrees per second
      and 90 degrees per second and using the Biodex balance system to evaluate
      stability index. RESULTS: The children in the experimental group showed a
      significant improvement when compared with those in the control group (P <
      0.001). The peak torque at 60 degrees per second and 90 degrees per second after
      treatment was 28.8 +/- 0.45 and 47.5 +/- 0.7 N . m and 30.9 +/- 0.68 and 54.2 +/-
      1.7 N . m for the control and the experimental group, respectively. The overall
      stability index after treatment was 2.75 and 2.2 for the control group and the
      experimental group, respectively. CONCLUSIONS: Whole-body vibration training may
      be a useful tool for improving muscle strength and balance in children with
      diplegic cerebral palsy.

PMID- 24434888
TI  - Feedback system based on plantar pressure for monitoring toe-walking strides in
      children with cerebral palsy.
AB  - OBJECTIVE: The aim of this study was to develop a feedback system to assist gait
      rehabilitation of cerebral palsy (CP) toe walkers with dynamic equinus. DESIGN:
      Plantar pressure of the forefoot and the heel was collected by sensorized insoles
      embedded in custom-built shoes and transmitted to a smartphone via Bluetooth.
      Dynamic foot pressure index of each stride was calculated by purpose-designed
      software running in the smartphone to distinguish toe-walking strides from normal
      strides in real time. An auditory signal would be produced to alert the patient
      each time a toe-walking stride was detected. RESULTS: For CP toe walkers, the one
      way analysis of variance indicated a significant difference (F1,14 = 19.492, P =
      0.001) in dynamic foot pressure index between the affected side (31.4 +/- 12.0)
      and the unaffected side (58.6 +/- 2.5). In addition, the validation test showed
      that this system can distinguish toe-walking strides from normal strides of
      children with CP with an accuracy of 95.3%. CONCLUSIONS: This system was able to
      monitor the toe-walking strides of children with CP in real time and had the
      potential to enhance rehabilitation training efficiency and correct toe-walking
      gait in children with CP with dynamic equinus.

PMID- 24434889
TI  - Effects of upper thoracic manipulation on pressure pain sensitivity in women with
      temporomandibular disorder: a randomized, double-blind, clinical trial.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effects of upper
      thoracic manipulation on pain in subjects with temporomandibular disorder.
      DESIGN: Thirty-two women with a diagnosis of temporomandibular disorder were
      randomly allocated to an experimental group (n = 16), submitted to upper thoracic
      manipulation, and a placebo group (n = 16), submitted to a procedure in the
      thoracic region with no therapeutic effect. All volunteers underwent an
      evaluation of pain in the masticatory muscles and the temporomandibular joint
      using an algometer and the visual analog scale before and immediately after the
      procedure as well as after 48-72 hrs. Two-way repeated-measures analysis of
      variance was used for the intragroup and intergroup analyses, with the level of
      significance set to 5% (P < 0.05). Cohen d was calculated for the determination
      of the effect size. RESULTS: No significant group-by-time interaction was found
      (P > 0.05) for algometry in any analysis, and Cohen d revealed no significant
      effect of the treatment. Moreover, no significant group-by-time interaction was
      found for facial pain intensity determined using the visual analog scale (P >
      0.05), and Cohen d also revealed no significant effect of the treatment regarding
      this variable. CONCLUSIONS: On the basis of the present findings, upper thoracic
      spinal manipulation does not lead to a reduction in pain in women with
      temporomandibular disorder.

PMID- 24434890
TI  - Ascertaining maximal voluntary effort production during isokinetic knee strength
      testing of anterior cruciate ligament-reconstructed patients.
AB  - OBJECTIVE: The aim of this study was to assess the performance of prediction
      rules meant for declaration of efforts as being maximal or not during isokinetic
      strength testing in a cohort that underwent anterior cruciate ligament
      reconstruction. DESIGN: Thirty-six individuals performed four sets of six
      reciprocal concentric knee extension/flexion repetitions at a testing speed of 60
      degrees per second through a 60-degree range of motion. The sets consisted of a
      maximal voluntary effort, two nonmaximal sincere efforts at 50% and 75% of self
      perceived maximum, and a set attempting to feign or exaggerate thigh muscle
      strength deficiencies. Strength curve derived set internal consistency measures,
      namely, cross-correlation and percent root mean square difference scores, were
      inputted into the prediction rules, whose performance is reported as specificity
      and sensitivity percentages. RESULTS: Dependent on the prediction rule used and
      when expressed on an individual participant basis, the corresponding specificity
      and sensitivity values ranged from 66.6% to 97.2% and 97.2% to 94.4%,
      respectively. CONCLUSIONS: Using the prediction rules presented in this
      investigation, clinicians may be able to ascertain maximal effort production
      during isokinetic testing in those who have undergone surgical reconstruction of
      their anterior cruciate ligament.

PMID- 24434891
TI  - Musculoskeletal ultrasound imaging of the recently described anterolateral
      ligament of the knee.

PMID- 24434893
TI  - Chiral phenoxyimino-amido aluminum complexes for the asymmetric cyanation of
      aldehydes.
AB  - The reactivity of triethylaluminum towards salicylaldimine sulfonamides was
      probed, affording well-defined complexes through consecutive protonolysis of two
      Al-C bonds by the proligand. These complexes, when combined with an achiral
      anilinic N-oxide, catalyze the asymmetric addition of trimethylsilylcyanide to a
      wide range of aldehydes, with good activity and enantioselectivity (up to 91%
      ee). Insertion of the benzaldehyde substrate into the Al-N amido bond was
      observed, bringing elements for discussion around the nature of the actual active
      species. 

PMID- 24434894
TI  - Electrical impedance of mouse brain cortex in vitro from 4.7 kHz to 2.0 MHz.
AB  - The electrical impedance of samples of mouse brain cortex has been measured
      between 4.7 kHz and 2.0 MHz. Brain slices of thickness 400 MUm were prepared from
      two mice. Each slice was placed in either normal artificial cerebrospinal fluid
      or magnesium-free artificial cerebrospinal fluid; the latter induces seizure-like
      electrical behaviour. A total of 74 samples of cortex of approximate size 2 mm *
      2 mm were then cut from these slices. Each sample in turn was placed between two
      flat Ag/AgCl electrodes and electrical impedance measured with an Agilent E4980A
      four-point impedance monitor. The measurements showed two regions of significant
      dispersion. Circuits based on the Cole-Cole and Fricke models, consisting of
      inductive, nonlinear capacitive and resistive elements were used to model the
      behaviour. Distributions of values for each circuit element have been determined
      for the samples prepared in seizing and non-seizing conditions. Few differences
      were found between the values of circuit elements between the seizing and non
      seizing groups. 

PMID- 24434892
TI  - Liver-specific agents for contrast-enhanced MRI: role in oncological imaging.
AB  - Liver-specific magnetic resonance (MR) contrast agents are increasingly used in
      evaluation of the liver. They are effective in detection and morphological
      characterization of lesions, and can be useful for evaluation of biliary tree
      anatomy and liver function. The typical appearances and imaging pitfalls of
      various tumours at MR imaging performed with these agents can be understood by
      the interplay of pharmacokinetics of these contrast agents and transporter
      expression of the tumour. This review focuses on the applications of these agents
      in oncological imaging. 

PMID- 24434895
TI  - Effect of magnet recognition on provision of smoking cessation advice to
      inpatients with pneumonia.
AB  - The study examined the effect of Magnet recognition on hospital-reported rates of
      smoking cessation advice (SCA) provided to inpatients with community-acquired
      pneumonia. Logistic and propensity score regression models estimated the magnet
      effect on the SCA rate. Predictors were hospital characteristics, socioeconomic
      factors affecting smoking, and baseline and mid-study SCA rates as variations in
      hospital-improvement systems. Magnet recognized hospitals reporting higher mid
      study SCA rates had higher outcome SCA rates.

PMID- 24434896
TI  - Determinants and outcomes of ventriculoperitoneal shunt infections in Enugu,
      Nigeria.
AB  - BACKGROUND: To evaluate the determinants and outcomes of shunt infection (SI).
      METHODS: One hundred ninety-eight pediatric hydrocephalic patients treated with a
      ventriculoperitoneal (VP) shunt between January 2008 and August 2012 were
      retrospectively studied. Patients with SI were compared to those without SI in
      terms of the occurrence of risk factors and outcomes. Data was analyzed using
      Statistical Package for the Social Sciences software (version 15). RESULTS: The
      age range was 2 weeks to 13 years, with a mean age of 3.1 +/- 0.19 years for the
      SI group versus 2.7 +/- 0.2 years for those without SI. One hundred and twelve
      patients were female and 86 were male. SI was recorded in 17 (8.6%) patients.
      Postinfective hydrocephalus (n = 6) was the most common cause of hydrocephalus in
      the SI group. Individuals in the SI group, compared to those without infection,
      were more likely to be underweight (chi2 = 23.4, p < 0.01). The mean interval
      between VP shunt placement and SI was 1.83 +/- 1.25 months. Coagulase-negative
      Staphylococcus (29.4%) was the most common pathogen. The mortality rate in our
      series was 21.4% in patients with SI compared to 2.7% in those without SI.
      CONCLUSION: Coagulase-negative Staphylococcus is currently the most common cause
      of SI and underweight children appear have a higher risk.

PMID- 24434897
TI  - Tumor deposits in rectal adenocarcinoma after neoadjuvant chemoradiation are
      associated with poor prognosis.
AB  - Although tumor deposits have been associated with poor prognosis in colorectal
      carcinoma, the prevalence and clinical significance of tumor deposits in rectal
      adenocarcinoma following neoadjuvant chemoradiation are relatively unexplored.
      The aims of this study are to assess the clinical significance of tumor deposits
      in rectal adenocarcinoma patients, including those receiving neoadjuvant therapy.
      Pathology slides and medical records from 205 consecutive patients who underwent
      resection for rectal adenocarcinoma between 1990 and 2010 at a single tertiary
      care center were reviewed. Patients with tumor deposits had higher tumor grade
      (P=0.006) and worse tumor stage (P<0.001) at presentation than patients without
      tumor deposits. Among 110 patients who underwent neoadjuvant chemoradiation,
      tumor deposits were associated with higher rates of lymph node involvement
      (P=0.035) and distant metastases (P=0.006), and decreased survival (P=0.027).
      These patients had a trend toward lower treatment response scores (P=0.285) and
      higher local recurrence (P=0.092). Of 52 patients with tumor deposits, those who
      underwent neoadjuvant chemoradiation had significantly worse pretreatment stage
      by endoscopic ultrasound (P<0.001) but interestingly had significantly lower
      rates of lymphovascular invasion on resection (P<0.001) compared with those who
      had not received neoadjuvant chemoradiation. Despite treatment with neoadjuvant
      chemoradiation, tumor deposits were present in over one-fifth of rectal
      adenocarcinoma patients. Overall, the outcome of patients with tumor deposits in
      treated and untreated patients were similar, however the association of tumor
      deposits with deeply invasive tumors and less tumor regression when comparing
      with treated patients without tumor deposits raises the possibility that these
      tumors could have a more aggressive biology, possibly explaining the association
      of tumor deposits with higher rates of recurrence and lower survival after
      neoadjuvant chemoradiation. Overall, tumor deposits appear to be a poor
      prognostic marker among rectal adenocarcinoma patients following neoadjuvant
      chemoradiation and may identify a subset of patients who require aggressive
      adjuvant therapy to prevent recurrence. 

PMID- 24434898
TI  - Biomarker evaluation of face transplant rejection: association of donor T cells
      with target cell injury.
AB  - This series of 113 sequential biopsies of full facial transplants provides
      findings of potential translational significance as well as biological insights
      that could prompt reexamination of conventional paradigms of effector pathways in
      skin allograft rejection. Serial biopsies before, during, and after rejection
      episodes were evaluated for clinicopathological assessment that in selected cases
      included specific biomarkers for donor-versus-recipient T cells. Histologic
      evidence of rejection included lymphocyte-associated injury to epidermal rete
      ridges, follicular infundibula, and dermal microvessels. Surprisingly, during
      active rejection, immune cells spatially associated with target cell injury
      consisted abundantly or predominantly of lymphocytes of donor origin with an
      immunophenotype typical of the resident memory T-cell subset. Current dogma
      assumes that skin allograft rejection is mediated by recipient T cells that
      attack epidermal targets, and the association of donor T cells with sites of
      target cell injury raises questions regarding the potential complexity of immune
      cell interactions in the rejection process. A more histopathologically refined
      and immune-based biomarker approach to assessment of rejection of facial
      transplants is now indicated. 

PMID- 24434900
TI  - Comparative diagnostic and prognostic performances of the hematoxylin-eosin and
      phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma.
AB  - Mitotic count on hematoxylin and eosin slides is a fundamental morphological
      criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring
      system employed. Moreover, it is the unique term strongly associated with
      patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was
      already proven to facilitate mitotic count in melanoma and other tumors.
      Therefore, a study was designed to assess the diagnostic and prognostic role of
      phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and
      computerized count to standard manual hematoxylin- and eosin-based method and Ki
      67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were
      highly correlated (r=0.9077, P<0.0001), better than computer-assisted phospho
      histone H3 evaluations, and had an excellent inter-observer reproducibility at
      Bland-Altman analysis. Three of 15 cases having <5 mitotic figures per 50 high
      power fields by standard count on hematoxylin and eosin gained the mitotic figure
      point of Weiss Score after a manual count on phospho-histone H3 slides.
      Traditional mitotic count confirmed to be a strong predictor of overall survival
      (P=0.0043), better than phospho-histone H3-based evaluation (P=0.051), but not as
      strong as the Ki-67 index (P<0.0001). The latter further segregated
      adrenocortical carcinomas into three prognostic groups, stratifying cases by low
      (<20%), intermediate (20-50%), and high (>50%) Ki-67 values. We conclude that (a)
      phospho-histone H3 staining is a useful diagnostic complementary tool to standard
      hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation
      (including atypical mitotic figures) even in adrenocortical carcinomas with a low
      mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the
      best prognostic indicator of overall survival, being superior to the mitotic
      index, irrespective of the method (standard on hematoxylin and eosin or phospho
      histone H3-based) used to count mitotic figures. 

PMID- 24434901
TI  - Chemical consequences of mechanical bonding in catenanes and rotaxanes:
      isomerism, modification, catalysis and molecular machines for synthesis.
AB  - Research on mechanically interlocked molecules has advanced substantially over
      the last five decades. A large proportion of the published work focusses on the
      synthesis of these challenging targets, and the subsequent control of the
      relative position of the covalent sub-components, to generate novel molecular
      devices and machines. In this Feature Article we instead review some of the less
      discussed consequences of mechanical bonding for the chemical behaviour of
      catenanes and rotaxanes, and their application in synthesis, including striking
      recent examples of molecular machines which carry out complex synthetic tasks. 

PMID- 24434899
TI  - Evaluation of stromal HGF immunoreactivity as a biomarker for melanoma response
      to RAF inhibitors.
AB  - Of more than 150 000 published studies evaluating new biomarkers, fewer than 100
      biomarkers have been implemented for patient care. One reason for this is lack of
      rigorous testing by the medical community to validate claims for biomarker
      clinical relevance, and potential reluctance to publish negative results when
      confirmation is not obtained. Here we sought to determine the utility and
      reproducibility of immunohistochemical detection of hepatocyte growth factor
      (HGF) in melanoma tissue, an approach of potential assistance in defining
      patients with innate resistance to BRAF inhibitor therapy. To this end, a
      published and a revised method that retained sensitivity but with greater
      specificity for HGF detection, were evaluated in cells known to endogenously
      express HGF, and in models where HGF is upregulated via cytokine induction and
      via overexpression by gene transfection. Consequent patient evaluation in
      collaboration with the Melanoma Institute Australia of a cohort of 41 melanoma
      specimens with extensive clinical annotation failed to validate HGF
      immunohistochemistry as a predictor of response to BRAF inhibitors. Targeted
      therapies for advanced melanoma and other cancers show great promise, and
      rigorous validation studies are thus indicated for approaches that seek to
      personalize such therapies to maximize therapeutic efficacy. 

PMID- 24434902
TI  - Initial stages of Cu3Au(111) oxidation: oxygen induced Cu segregation and the
      protective Au layer profile.
AB  - We report results of our experimental and theoretical studies on the Au
      concentration profile of Cu3Au(111) during oxidation by a hyperthermal O2
      molecular beam at room temperature, using X-ray photoemission spectroscopy (XPS),
      in conjunction with synchrotron radiation (SR), and density functional theory
      (DFT). Before O2 exposure, we observe strong Au segregation to the top layer,
      i.e., Au surface enrichment of the clean surface. We also observe a gradual Cu
      surface enrichment, and Au enrichment of the second and third (subsurface)
      layers, with increasing O coverage. Complete Cu segregation to the surface occurs
      at 0.5 ML O surface coverage. The Au-rich second and third layers of the oxidized
      surface demonstrate the protective layer formation against oxidation deeper into
      the bulk. 

PMID- 24434903
TI  - Proteomic and functional consequences of hexokinase deficiency in glucose
      repressible Kluyveromyces lactis.
AB  - The analysis of glucose signaling in the Crabtree-positive eukaryotic model
      organism Saccharomyces cerevisiae has disclosed a dual role of its hexokinase
      ScHxk2, which acts as a glycolytic enzyme and key signal transducer adapting
      central metabolism to glucose availability. In order to identify evolutionarily
      conserved characteristics of hexokinase structure and function, the cellular
      response of the Crabtree-negative yeast Kluyveromyces lactis to rag5 null
      mutation and concomitant deficiency of its unique hexokinase KlHxk1 was analyzed
      by means of difference gel electrophoresis. In total, 2,851 fluorescent spots
      containing different protein species were detected in the master gel representing
      all of the K. lactis proteins that were solubilized from glucose-grown KlHxk1
      wild-type and mutant cells. Mass spectrometric peptide analysis identified 45
      individual hexokinase-dependent proteins related to carbohydrate, short-chain
      fatty acid and tricarboxylic acid metabolism as well as to amino acid and protein
      turnover, but also to general stress response and chromatin remodeling, which
      occurred as a consequence of KlHxk1 deficiency at a minimum 3-fold enhanced or
      reduced level in the mutant proteome. In addition, three proteins exhibiting
      homology to 2-methylcitrate cycle enzymes of S. cerevisiae were detected at
      increased concentrations, suggesting a stimulation of pyruvate formation from
      amino acids and/or fatty acids. Experimental validation of the difference gel
      electrophoresis approach by post-lysis dimethyl labeling largely confirmed the
      abundance changes detected in the mutant proteome via the former method. Taking
      into consideration the high proportion of identified hexokinase-dependent
      proteins exhibiting increased proteomic levels, KlHxk1 is likely to have a
      repressive function in a multitude of metabolic pathways. The proteomic
      alterations detected in the mutant classify KlHxk1 as a multifunctional enzyme
      and support the view of evolutionary conservation of dual-role hexokinases even
      in organisms that are less specialized than S. cerevisiae in terms of glucose
      utilization. 

PMID- 24434904
TI  - A new simple concept for ocean colour remote sensing using parallel polarisation
      radiance.
AB  - Ocean colour remote sensing has supported research on subjects ranging from
      marine ecosystems to climate change for almost 35 years. However, as the
      framework for ocean colour remote sensing is based on the radiation intensity at
      the top-of-atmosphere (TOA), the polarisation of the radiation, which contains
      additional information on atmospheric and water optical properties, has largely
      been neglected. In this study, we propose a new simple concept to ocean colour
      remote sensing that uses parallel polarisation radiance (PPR) instead of the
      traditional radiation intensity. We use vector radiative transfer simulation and
      polarimetric satellite sensing data to demonstrate that using PPR has two
      significant advantages in that it effectively diminishes the sun glint
      contamination and enhances the ocean colour signal at the TOA. This concept may
      open new doors for ocean colour remote sensing. We suggest that the next
      generation of ocean colour sensors should measure PPR to enhance observational
      capability. 

PMID- 24434906
TI  - Stereoselective Luche reduction of deoxynivalenol and three of its acetylated
      derivatives at C8.
AB  - The trichothecene mycotoxin deoxynivalenol (DON) is a well known and common
      contaminant in food and feed. Acetylated derivatives and other biosynthetic
      precursors can occur together with the main toxin. A key biosynthetic step
      towards DON involves an oxidation of the 8-OH group of 7,8-dihydroxycalonectrin.
      Since analytical standards for the intermediates are not available and these
      intermediates are therefore rarely studied, we aimed for a synthetic method to
      invert this reaction, making a series of calonectrin-derived precursors
      accessible. We did this by developing an efficient protocol for stereoselective
      Luche reduction at C8. This method was used to access 3,7,8,15
      tetrahydroxyscirpene, 3-deacetyl-7,8-dihydroxycalonectrin, 15-deacetyl-7,8
      dihydroxycalonectrin and 7,8-dihydroxycalonectrin, which were characterized using
      several NMR techniques. Beside the development of a method which could basically
      be used for all type B trichothecenes, we opened a synthetic route towards
      different acetylated calonectrins. 

PMID- 24434908
TI  - Future directions in nutrition research.

PMID- 24434905
TI  - Toxin-antitoxin systems as multilevel interaction systems.
AB  - Toxin-antitoxin (TA) systems are small genetic modules usually composed of a
      toxin and an antitoxin counteracting the activity of the toxic protein. These
      systems are widely spread in bacterial and archaeal genomes. TA systems have been
      assigned many functions, ranging from persistence to DNA stabilization or
      protection against mobile genetic elements. They are classified in five types,
      depending on the nature and mode of action of the antitoxin. In type I and III,
      antitoxins are RNAs that either inhibit the synthesis of the toxin or sequester
      it. In type II, IV and V, antitoxins are proteins that either sequester,
      counterbalance toxin activity or inhibit toxin synthesis. In addition to these
      interactions between the antitoxin and toxin components (RNA-RNA, protein
      protein, RNA-protein), TA systems interact with a variety of cellular factors,
      e.g., toxins target essential cellular components, antitoxins are degraded by
      RNAses or ATP-dependent proteases. Hence, TA systems have the capacity to
      interact with each other at different levels. In this review, we will discuss the
      different interactions in which TA systems are involved and their implications in
      TA system functions and evolution. 

PMID- 24434909
TI  - Age-related consequences of childhood obesity.
AB  - The severity and frequency of childhood obesity has increased significantly over
      the past three to four decades. The health effects of increased body mass index
      as a child may significantly impact obese youth as they age. However, many of the
      long-term outcomes of childhood obesity have yet to be studied. This article
      examines the currently available longitudinal data evaluating the effects of
      childhood obesity on adult outcomes. Consequences of obesity include an increased
      risk of developing the metabolic syndrome, cardiovascular disease, type 2
      diabetes and its associated retinal and renal complications, nonalcoholic fatty
      liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility,
      asthma, orthopedic complications, psychiatric disease, and increased rates of
      cancer, among others. These disorders can start as early as childhood, and such
      early onset increases the likelihood of early morbidity and mortality. Being
      obese as a child also increases the likelihood of being obese as an adult, and
      obesity in adulthood also leads to obesity-related complications. This review
      outlines the evidence for childhood obesity as a predictor of adult obesity and
      obesity-related disorders, thereby emphasizing the importance of early
      intervention to prevent the onset of obesity in childhood.

PMID- 24434911
TI  - Addiction: pregnenolone limits effects of cannabis.

PMID- 24434913
TI  - Synaptic plasticity: a synaptic role for microglia.

PMID- 24434910
TI  - Sensory-evoked synaptic integration in cerebellar and cerebral cortical neurons.
AB  - Neurons integrate synaptic inputs across time and space, a process that
      determines the transformation of input signals into action potential output. This
      article explores how synaptic integration contributes to the richness of sensory
      signalling in the cerebellar and cerebral cortices. Whether a neuron receives a
      few or a few thousand discrete inputs, most evoked synaptic activity generates
      only subthreshold membrane potential fluctuations. Sensory tuning of synaptic
      inputs is typically broad, but short-term dynamics and the interplay between
      excitation and inhibition restrict action potential firing to narrow windows of
      opportunity. We highlight the challenges and limitations of the use of somatic
      recordings in the study of synaptic integration and the importance of active
      dendritic mechanisms in sensory processing. 

PMID- 24434914
TI  - Engineering of a Pluronic F127 functionalized magnetite/graphene nanohybrid for
      chemophototherapy.
AB  - In this study, a multifunctional graphene based nanohybrid, termed as
      GN/Fe3O4/PF127, is engineered via a facile one-pot process consisting of
      simultaneous reduction of graphene oxide/Fe3O4 and subsequent assembly of
      Pluronic F127 (PF127) onto graphene nanosheets (GNs). The unique aromatic and
      planar structure of GNs allows the attachment of multiple functional components
      including MRI contrast agent (Fe3O4 nanoparticles) and an aromatic anticancer
      drug like doxorubicin (DOX), as well as PF127 coating which imparts physiological
      dispersivity and stability to the nanohybrid. The successful assembly process is
      revealed by TEM observation, size and FITR monitoring. In contrast with the
      primitive graphene or its oxide derivative, the resulting GN/Fe3O4/PF127
      nanohybrids have shown high biological dispersion and MRI effect for diagnosis
      due to the incorporation of superparamagnetic Fe3O4 nanoparticles without evident
      cytotoxicity. Moreover, the GN/Fe3O4/PF127 nanohybrid exhibits a photothermal
      effect due to the considerable optical absorption in the near-infrared region of
      GNs. The GN/Fe3O4/PF127 nanohybrid could be a further platform for
      chemophototherapy assisted by the therapeutic DOX. Cellular toxicity assays
      indicated that the DOX-loaded GN/Fe3O4/PF127 nanohybrid showed a remarkable
      cytotoxicity to HeLa cells and the cytotoxic effect was intensified when
      subjected to photoirradiation. Confocal laser scanning microscopy (CLSM) and flow
      cytometric analysis (FCAS) revealed that the nanohybrid could be easily uptaken
      into HeLa cells. 

PMID- 24434912
TI  - Oscillatory multiplexing of population codes for selective communication in the
      mammalian brain.
AB  - Mammalian brains exhibit population oscillations, the structures of which vary in
      time and space according to behavioural state. A proposed function of these
      oscillations is to control the flow of signals among anatomically connected
      networks. However, the nature of neural coding that may support selective
      communication that depends on oscillations has received relatively little
      attention. Here, we consider the role of multiplexing, whereby multiple
      information streams share a common neural substrate. We suggest that multiplexing
      implemented through periodic modulation of firing-rate population codes enables
      flexible reconfiguration of effective connectivity among brain areas.

PMID- 24434915
TI  - Assessment of speed distribution of red blood cells in the microvascular network
      in healthy volunteers and type 1 diabetes using laser Doppler spectra
      decomposition.
AB  - We applied a recently reported method of decomposition of laser Doppler power
      density spectra for in vivo monitoring of speed distributions of red blood cells
      (RBCs) in the microvascular network. The spectrum decomposition technique allows
      us to derive the distribution of RBC speed (in absolute units (mm s(-1))) versus
      RBC concentration (in arbitrary units). We carried out postocclusive reactive
      hyperaemia (PORH) test in 15 healthy volunteers and 21 diabetic patients in which
      the duration of type 1 diabetes was longer than 10 years. Measurements were
      carried out simultaneously with the use of a typical laser Doppler commercial
      instrument and speed resolved laser Doppler instrument utilizing the new
      technique based on decomposition of the laser Doppler spectra. We show that for
      the classical laser Doppler instrument, none of the PORH parameters revealed a
      statistical significance of difference between the groups analyzed. In contrast,
      the RBC speed distributions obtained from laser Doppler spectra during rest in
      the control group and type 1 diabetes are statistically significant. This result
      suggests that speed distribution measurements in the rest state (without any kind
      of stimulation test) allows for the assessment of microcirculation disorders.
      Measurements carried out in healthy subjects show that the first moment of speed
      distributions (mean speed of the distributions) is 2.32 +/- 0.54 mm s(-1) and
      2.57 +/- 0.41 mm s(-1) for optodes located on the toe and finger of the hand,
      respectively. Respective values in type 1 diabetes were higher: 3.00 +/- 0.36 mm
      s(-1) and 3.10 +/- 0.48 mm s(-1). 

PMID- 24434916
TI  - The minimally invasive, orbicularis-sparing, lower eyelid recession for mild to
      moderate lower eyelid retraction with reduced orbicularis strength.
AB  - IMPORTANCE Identifying a procedure to address lower eyelid retraction (LER) in
      the presence of an orbicularis deficit is a useful tool for aesthetic and
      reconstructive eyelid surgery. OBJECTIVE To describe and evaluate a surgical
      technique consisting of a closed canthal suspension and true lower eyelid
      retractor recession to address LER in the setting of orbicularis weakness.
      DESIGN, SETTING, AND PARTICIPANTS A retrospective medical record review of
      patients who underwent the minimally invasive, orbicularis-sparing, lower eyelid
      recession from January 1, 2010, to October 1, 2012, by one of us (G.G.M.) in an
      ophthalmic plastic surgical practice. We included 29 patients with reduced
      orbicularis strength and LER resulting from eyelid paresis related to facial
      nerve disease, surgical trauma (after blepharoplasty), involutional change, or
      idiopathic causes. INTERVENTIONS Surgical intervention consisting of closed
      canthal suspension and lower eyelid retractor recession. MAIN OUTCOMES AND
      MEASURES Surgical results, complications, and patient satisfaction. RESULTS The
      29 patients included 18 women and 11 men. The mean patient age was 52 (range, 6
      72) years; mean follow-up, 11 (range, 6-21) months; and mean preoperative
      orbicularis strength, 2.7 (on a scale of 0-4, where 0 indicates no function and
      4, normal function). The causes of orbicularis weakness included eyelid paresis
      related to facial nerve disease (11 patients), surgical trauma (13 patients),
      involutional change (4 patients), and an isolated idiopathic finding (1 patient).
      In 12 patients, the eyelid retraction was unilateral; in 17, bilateral. A small
      tarsorrhaphy was added to the surgery in 6 patients with facial nerve disease.
      The mean eyelid elevation after surgery was 1.80 mm, with only minor
      complications. Patient and surgeon satisfaction were high. CONCLUSIONS AND
      RELEVANCE Recent publications have demonstrated the utility of closed canthal
      suspension and true lower eyelid retractor recession as separate procedures. In
      the setting of LER with reduced orbicularis strength and/or tone, the techniques
      can be combined to recess the lower eyelid without disturbing the already
      compromised lower orbicularis muscle (minimally invasive, orbicularis-sparing,
      lower eyelid recession). The combination technique is safe and effective and
      yields excellent results. LEVEL OF EVIDENCE 4. 

PMID- 24434917
TI  - Differences in the maturation of amplitude-integrated EEG signals in male and
      female preterm infants.
AB  - BACKGROUND: The amplitude-integrated electroencephalogram (aEEG) is a valuable
      tool for monitoring brain function in preterm infants. Several studies have
      discussed sex-related differences regarding neonatal morbidity and mortality. To
      date, no study has been published specifically evaluating potential sex-related
      differences in aEEG parameters. OBJECTIVE: The aim of this study was to assess
      sex-related differences in aEEG signals in preterm born infants without brain
      injury in the first 4 weeks of life. METHODS: aEEG was performed at seven time
      points (days 1, 2, 3, weeks 1, 2, 3 and 4) and analyzed for Burdjalov total
      score, number of bursts per hour and visual background pattern. PATIENTS: One
      hundred and fifty-six infants (85 male and 71 female) born with a gestational age
      between 28 and 31 completed weeks were evaluated. RESULTS: Mean total score
      increased with postnatal age and ranged from 5.4 at day 1 to 11.0 at the end of
      the study period. The score was higher for girls at every time point, and the
      mean difference was between 0.3 and 0.9. The number of bursts per hour decreased
      over time from 8.9 at day 1 to 1.6 at the end of the study period. At week 4, the
      number of bursts per hour was significantly lower in girls (1.3) than in boys
      (2.0). CONCLUSION: Sex-related differences were present in aEEG signals of
      preterm infants. The lower total score and the higher number of bursts might
      express delayed brain maturation in male preterm infants.

PMID- 24434918
TI  - Three-dimensional volume-rendered multidetector CT imaging of the posterior
      inferior pancreaticoduodenal artery: its anatomy and role in diagnosing
      extrapancreatic perineural invasion.
AB  - Extrapancreatic perineural spread in pancreatic adenocarcinoma contributes to
      poor outcomes, as it is known to be a major contributor to positive surgical
      margins and disease recurrence. However, current staging classifications have not
      yet taken extrapancreatic perineural spread into account. Four pathways of
      extrapancreatic perineural spread have been described that conveniently follow
      small defined arterial pathways. Small field of view three-dimensional (3D)
      volume-rendered multidetector computed tomography (MDCT) images allow
      visualization of small peripancreatic vessels and thus perineural invasion that
      may be associated with them. One such vessel, the posterior inferior
      pancreaticoduodenal artery (PIPDA), serves as a surrogate for extrapancreatic
      perineural spread by pancreatic adenocarcinoma arising in the uncinate process.
      This pictorial review presents the normal and variant anatomy of the PIPDA with
      3D volume-rendered MDCT imaging, and emphasizes its role as a vascular landmark
      for the diagnosis of extrapancreatic perineural invasion from uncinate
      adenocarcinomas. Familiarity with the anatomy of PIPDA will allow accurate
      detection of extrapancreatic perineural spread by pancreatic adenocarcinoma
      involving the uncinate process, and may potentially have important staging
      implications as neoadjuvant therapy improves. 

PMID- 24434919
TI  - Pillar[5]arene-based diglycolamides for highly efficient separation of
      americium(III) and europium(III).
AB  - Pillar[5]arenes, as a new intriguing class of calixarene analogues, were
      functionalized with ten diglycolamide (DGA) arms on both sides (rims) of the
      pillar framework and evaluated for their extraction behaviour towards Am(III) and
      Eu(III). These novel extractants exhibit excellent separation and extraction
      efficiency, suggesting its significant potential for nuclear waste remediation.
      Laser induced fluorescence experiments disclosed strong complexation of the
      trivalent metal ions with the pillararene-DGA ligands.

PMID- 24434920
TI  - Dihydropyrimidine dehydrogenase 85T>C mutation is associated with ocular toxicity
      of 5-fluorouracil: a case report.
AB  - 5-Fluorouracil (5-FU), the mainstay of solid tumor chemotherapy over the past 40
      years, induces grade III-IV toxicities in up to 15% of patients with
      polymorphisms in the dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase
      (TYMS), and methylenetetrahydrofolate reductase (MTHFR) genes. These toxicities
      include mucositis, neutropenia, nausea, diarrhea, myelosuppression, hand-foot
      syndrome, and rare ocular adverse effects. Here, we present the case of a female
      patient with rectal cancer who received 5-FU-based chemotherapy and developed
      grade III hand-foot syndrome and rare acute ocular adverse effects. Genetic
      analysis revealed that the patient had an 85T>C mutation in the DPYD gene
      resulting in a DPYD*9A allele. The clinical and molecular observations indicate
      that DPYD deficiency may be responsible for the severe ocular adverse effects
      observed in 5-FU-treated patients. Application of personalized therapy based on
      molecular testing should help clinicians provide the most effective chemotherapy
      agents and dose modifications for each patient, although further population-based
      pharmacogenetic trials for the 5-FU metabolism-related genes are necessary to
      minimize adverse effects and enhance clinical outcomes. 

PMID- 24434923
TI  - Revisiting the Delphi technique: implications for nursing professional
      development.
AB  - The Delphi technique is a multistage survey involving rounds of structured
      questions with a panel of identified experts. The approach is well suited for a
      range of applications in nursing professional development practice that involve
      priority setting and consensus building. This article provides an overview of the
      technique, steps in using the approach, and implications and suggestions for its
      use in nursing professional development practice. 

PMID- 24434924
TI  - Preparing staff for intentional rounding: a process yielding success on a general
      surgical unit.
AB  - Intentional rounding is a strategicway to improve patient care through decreasing
      falls and hospital-acquired pressure ulcers, while increasing patient
      satisfaction. On the basis of literature reviews and discussions with nurses on
      units that pilot-tested intentional rounding, useful strategies emerged. This
      article will provide information about intentional rounding, a means for planning
      implementation, and the results of evaluating its implementation. 

PMID- 24434925
TI  - Transcultural advocacy and policy in the workplace: implications for nurses in
      professional development.
AB  - This article introduces the role of nursing professional development specialists
      in serving as a resource for both patient and staff advocacy regarding cultural
      and linguistic matters. The impact of changing demographics, support for civil
      rights, and established policy related to culture and linguistics is emphasized.
      An overview of policy at local, state, and national levels is suggested to
      promote nursing professional development in the interest of culturally and
      linguistically compliant nursing practice. 

PMID- 24434926
TI  - Evaluation of a reflective practice intervention to enhance hospitalized elderly
      care: a mixed method study.
AB  - The purpose of this mixed method study was to evaluate effects of a reflective
      practice intervention on the attitudes, knowledge, and interventions of nurses
      who care for hospitalized older adults. The study showed the potential of using a
      reflective practice intervention as a professional development approach to
      improve nurses' attitudes toward older adults. 

PMID- 24434927
TI  - Why are nurses so reluctant to implement changes based on evidence and what can
      we do to help?

PMID- 24434928
TI  - Nurse residency programs: why now?

PMID- 24434929
TI  - Developing skills in interpretation.

PMID- 24434930
TI  - Transforming NPD specialist practice through the integration of simulation
      modalities: becoming a simulation partner.

PMID- 24434934
TI  - Strengthening the skin with topical delivery of keratinocyte growth factor-1
      using a novel DNA plasmid.
AB  - Fragile skin, susceptible to decubitus ulcers and incidental trauma, is a problem
      particularly for the elderly and for those with spinal cord injury. Here, we
      present a simple approach to strengthen the skin by the topical delivery of
      keratinocyte growth factor-1 (KGF-1) DNA. In initial feasibility studies with the
      novel minimalized, antibiotic-free DNA expression vector, NTC8385-VA1, the
      reporter genes luciferase and enhanced green fluorescent protein were delivered.
      Transfection was documented when luciferase expression significantly increased
      after transfection. Microscopic imaging of enhanced green fluorescent protein
      transfected skin showed green fluorescence in hair follicles, hair shafts, and
      dermal and superficial epithelial cells. With KGF-1 transfection, KGF-1 mRNA
      level and protein production were documented with quantitative reverse
      transcriptase-polymerase chain reaction and immunohistochemistry, respectively.
      Epithelial thickness of the transfected skin in the KGF group was significantly
      increased compared with the control vector group (26 +/- 2 versus 16 +/- 4 um) at
      48 hours (P = 0.045). Dermal thickness tended to be increased in the KGF group
      (255 +/- 36 versus 162 +/- 16 um) at 120 hours (P = 0.057). Biomechanical
      assessment showed that the KGF-1-treated skin was significantly stronger than
      control vector-transfected skin. These findings indicate that topically delivered
      KGF-1 DNA plasmid can increase epithelial thickness and strength, demonstrating
      the potential of this approach to restore compromised skin. 

PMID- 24434936
TI  - Non-infantile desmoplastic cerebellar ganglioglioma in a patient with multiple
      congenital anomalies: a rare association.
AB  - Numerous syndromes with craniofacial, cardiac, cutaneous and vascular anomalies
      have been described in the literature. Here we report on a 9-year-old girl who
      was diagnosed as having a clavicular arteriovenous malformation with limb
      enlargement, an axillary port wine stain and macrocephaly with frontal bossing.
      She was investigated for enlarged head size; although she did not have
      hydrocephalus as initially suspected, she was found to have a right cerebellar
      lesion. This was excised and the pathology report was diagnostic of desmoplastic
      ganglioglioma. The posterior fossa is a very rare location for gangliogliomas.
      This was a desmoplastic variant that is only encountered in infants. Thus, the
      location and the pathology made the tumour rare. In addition, the cranio-vasculo
      cutaneous lesions made this previously unreported association noteworthy.

PMID- 24434935
TI  - Modified lentiviral LTRs allow Flp recombinase-mediated cassette exchange and in
      vivo tracing of "factor-free" induced pluripotent stem cells.
AB  - Methods for generating induced pluripotent stem cells (iPSCs) for disease
      modeling and cell therapies have progressed from integrating vectors to transient
      delivery of reprogramming factors, avoiding permanent genomic modification. A
      major limitation of unmodified iPSCs is the assessment of their distribution and
      contribution to adverse reactions in autologous cell therapy. Here, we report
      that polycistronic lentiviral vectors with single Flp recombinase (Flp)
      recognition target (FRT) sites can be used to generate murine iPSCs that are
      devoid of the reprogramming cassette but carry an intergenic 300-bp long terminal
      repeat sequence. Performing quantitative polymerase chain reaction on this
      marker, we could determine genetic identity and tissue contribution of iPSC
      derived teratomas in mice. Moreover, we generated iPSCs carrying heterospecific
      FRT twin sites, enabling excision and recombinase-mediated cassette exchange
      (RMCE) of the reprogramming cassette for another expression unit of choice.
      Following screening of iPSCs for "safe harbor" integration sites, expression
      cassettes were introduced by RMCE into various previously silenced loci of
      selected single-copy iPSCs. Analysis of DNA methylation showed that RMCE reverted
      the local epigenetic signature, which allowed transgene expression in
      undifferentiated iPSCs and in differentiated progeny. These findings support the
      concept of creating clonotypically defined exchangeable and traceable pluripotent
      stem cells for disease research and cell therapy. 

PMID- 24434938
TI  - Analytic solution for the limiting shape of profiles due to fretting wear.
AB  - We consider fretting wear due to tangential oscillations of two contacting
      bodies. For small oscillation amplitudes, the wear occurs only in a circular slip
      zone at the border of the contact area. With increasing number of cycles, the
      wear profile tends to a limiting form, in which no further wear occurs. Under
      assumption of a constant coefficient of friction, the limiting form of the wear
      profile does not depend on the particular wear criterion and can be calculated
      analytically. An explicit analytic solution is presented for arbitrary initial
      shape and illustrated for the cases of parabolic and conical shapes. 

PMID- 24434937
TI  - Superior canal dehiscence length and location influences clinical presentation
      and audiometric and cervical vestibular-evoked myogenic potential testing.
AB  - Superior canal dehiscence (SCD) is caused by an absence of bony covering of the
      arcuate eminence or posteromedial aspect of the superior semicircular canal.
      However, the clinical presentation of SCD syndrome varies considerably, as some
      SCD patients are asymptomatic and others have auditory and/or vestibular
      complaints. In order to determine the basis for these observations, we examined
      the association between SCD length and location with: (1) auditory and vestibular
      signs and symptoms; (2) air conduction (AC) loss and air-bone gap (ABG) measured
      by pure-tone audiometric testing, and (3) cervical vestibular-evoked myogenic
      potential (cVEMP) thresholds. 104 patients (147 ears) underwent SCD length and
      location measurements using a novel method of measuring bone density along 0.2-mm
      radial CT sections. We found that patients with auditory symptoms have a larger
      dehiscence (median length: 4.5 vs. 2.7 mm) with a beginning closer to the ampulla
      (median location: 4.8 vs. 6.4 mm from ampulla) than patients with no auditory
      symptoms (only vestibular symptoms). An increase in AC threshold was found as the
      SCD length increased at 250 Hz (95% CI: 1.7-4.7), 500 Hz (95% CI: 0.7-3.5) and
      1,000 Hz (95% CI: 0.0-2.5), and an increase in ABG as the SCD length increased at
      250 Hz (95% CI: 2.0-5.3), 500 Hz (95% CI: 1.6-4.6) and 1,000 Hz (95% CI: 1.3-3.3)
      was also seen. Finally, a larger dehiscence was associated with lowered cVEMP
      thresholds at 250 Hz (95% CI: -4.4 to -0.3), 500 Hz (95% CI: -4.1 to -1.0), 750
      Hz (95% CI: -4.2 to -0.7) and 1,000 Hz (95% CI: -3.6 to -0.5) and a starting
      location closer to the ampulla at 250 Hz (95% CI: 1.3-5.1), 750 Hz (95% CI: 0.2
      3.3) and 1,000 Hz (95% CI: 0.6-3.5). These findings may help to explain the
      variation of signs and symptoms seen in patients with SCD syndrome.

PMID- 24434939
TI  - GPS source solution of the 2004 Parkfield earthquake.
AB  - We compute a series of finite-source parameter inversions of the fault rupture of
      the 2004 Parkfield earthquake based on 1 Hz GPS records only. We confirm that
      some of the co-seismic slip at shallow depth (<5 km) constrained by InSAR data
      processing results from early post-seismic deformation. We also show 1) that if
      located very close to the rupture, a GPS receiver can saturate while it remains
      possible to estimate the ground velocity (~1.2 m/s) near the fault, 2) that GPS
      waveforms inversions constrain that the slip distribution at depth even when GPS
      monuments are not located directly above the ruptured areas and 3) the slip
      distribution at depth from our best models agree with that recovered from strong
      motion data. The 95(th) percentile of the slip amplitudes for rupture velocities
      ranging from 2 to 5 km/s is ~55 +/- 6 cm. 

PMID- 24434940
TI  - A Ca(2+)-dependent signalling circuit regulates influenza A virus internalization
      and infection.
AB  - Various viruses enter host cells via endocytosis, but the molecular mechanisms
      underlying the specific internalization pathways remain unclear. Here we show
      that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin
      mediated and clathrin-independent endocytosis, with intracellular Ca(2+) having a
      central role in regulation of both pathways by activating a signalling axis
      comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K)
      and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic
      Ca(2+) concentration of host cells, the prevention of which markedly attenuates
      virus internalization and infection. The small GTPase RhoA is found both to
      function downstream of the virus-induced Ca(2+) response and itself to induce
      Ca(2+) oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC
      signalling. This signalling circuit regulates both clathrin-mediated and clathrin
      independent endocytosis during virus infection and seems to constitute a key
      mechanism for regulation of IAV internalization and infection. 

PMID- 24434941
TI  - Audiometric characteristics of a dutch family with a new mutation in GATA3
      causing HDR syndrome.
AB  - We present the case of a Dutch family with a new mutation (c523_528dup) in GATA3
      causing HDR syndrome. HDR syndrome is characterised by hypoparathyroidism,
      deafness and renal defects. In this study, we describe the audiometric
      characteristics of 5 patients from this family. Their hearing impairment was
      congenital, bilateral and symmetric. Audiograms showed mild-to-moderate hearing
      impairment with a flat audiogram configuration. Higher frequencies tended to be
      affected more strongly. Cross-sectional analyses showed no progression, and a
      mean audiogram was established. Psychophysical measurements in 3 HDR patients -
      including speech reception in noise, loudness scaling, gap detection and
      difference limen for frequency - were obtained to assess hearing function in
      greater detail. Overall, the results of the psychophysical measurements indicated
      characteristics of outer hair cell loss. CT scanning showed no anomalies in 3 of
      the HDR patients. Although 2 patients displayed vestibular symptoms, no anomalies
      in the vestibular system were found by vestibulo-ocular examination. Our results
      are in agreement with the theory that outer hair cell malfunctioning can play a
      major role in HDR syndrome.

PMID- 24434942
TI  - Quantum chemistry study of the oxidation-induced stability and decomposition of
      propylene carbonate-containing complexes.
AB  - Oxidation-induced decomposition reactions of the representative complexes of
      propylene carbonate (PC)-based electrolytes were investigated using density
      functional theory (DFT) and a composite G4MP2 method. The cluster-continuum
      approach was used, where the oxidized PCn cluster was surrounded by the implicit
      solvent modeled via a polarized continuum model (PCM). The oxidative stability of
      the PCn (n = 2, 3, and 4) complexes was found to be around 5.4-5.5 V vs.
      Li(+)/Li, which is not only lower than the stability of an isolated PC but also
      lower than the stability of the PC-PF6(-), PC-BF4(-) or PC-ClO4(-) complexes
      surrounded by the implicit solvent. The oxidation-induced decomposition reactions
      were studied. The decomposition products of the oxidized PC2 contained CO2,
      acetone, propanal, propene, and carboxylic acid in agreement with the previous
      experimental studies. 

PMID- 24434943
TI  - Falls and comorbidity: the pathway to fractures.
AB  - AIMS: To compare nationwide time trends and mortality in hip and proximal humeral
      fractures; to explore associations between incidences of falls risk related
      comorbidities (FRICs) and incidence of fractures. METHODS: The study is a
      retrospective cohort study using nationwide Danish administrative registries from
      2000 through 2009. Individuals aged 65 years or older who experienced a hip or a
      proximal humeral fracture were included. Incidence of hip and of proximal humeral
      fractures, incidence of FRICs (ischemic heart disease, COPD, dementia,
      depression, diabetes, heart failure, osteoporosis, Parkinson's disease and
      stroke) and incidence rate ratios (IRR) for fractures in patients with FRICs, and
      all-cause mortality up to 10 years after a hip or a proximal humeral fracture
      were analysed. RESULTS: A total of 89,150 patients experienced hip fractures and
      48,581 proximal humeral fractures. From 2000 through 2009, the incidence of hip
      fractures per 100,000 individuals declined by 198 (787 to 589, OR = 0.75, CI:
      0.72-0.80) among males and by 483 (1758 to 1275, OR = 0.74, CI: 0.72-0.77) among
      females. Incidences of FRICs decreased. The absolute reduction in fractures was
      most pronounced for the age group above 75 years (2393 to 1884, OR = 0.81, CI:
      0.78-0.83), but the relative reduction was more pronounced in the age group of 65
      75 years old (496 to 342, OR = 0.70, CI: 0.66-0.74). IRRs for hip fractures and
      for proximal humeral fractures were significantly elevated in patients with
      FRICs. CONCLUSIONS: The results suggest that the overall reduction in fractures
      can be explained by reduction in falls related comorbidity.

PMID- 24434944
TI  - A three-dimensional carbon nanotube network for water treatment.
AB  - The bulk synthesis of freestanding carbon nanotube (CNT) frameworks is developed
      through a sulfur-addition strategy during an ambient-pressure chemical vapour
      deposition process, with ferrocene used as the catalyst precursor. This approach
      enhances the CNTs' length and contorted morphology, which are the key features
      leading to the formation of the synthesized porous networks. We demonstrate that
      such a three-dimensional structure selectively uptakes from water a mass of toxic
      organic solvent (i.e. o-dichlorobenzene) about 3.5 times higher than that
      absorbed by individual CNTs. In addition, owing to the presence of highly
      defective nanostructures constituting them, our samples exhibit an oil-absorption
      capacity higher than that reported in the literature for similar CNT sponges.

PMID- 24434945
TI  - A comparison of intimate partner violence between Jordanian nurses and Jordanian
      women.
AB  - Intimate partner violence is a serious international problem. It is not known if
      the extent of intimate partner violence for Jordanian nurses is similar to that
      of Jordanian women. Until the rate is known, implementation of nursing
      interventions for Jordanian women may be thwarted. The study purpose was to
      determine the rate of intimate partner violence among Jordanian nurses working in
      governmental health settings in a northern city of Jordan and to compare the rate
      to published statistics for a community sample of Jordanian women. A cross
      sectional survey design was used for this study. A stratified random sample of 80
      Jordanian nurses working in governmental women's health centers and public
      hospitals in a northern city of Jordan was invited to participate. Institutional
      review board approval was granted. Participants completed the Woman Abuse
      Screening Tool in a private room at their work site. No identifiers were added to
      the survey forms. Chi-squared goodness-of-fit tests were computed to compare the
      rate of intimate partner violence between the study sample and reported
      statistics for Jordanian women. Approximately 59% of participants experienced
      psychological violence, 12.5% experienced physical violence, and 5.1% experienced
      sexual violence. No significant differences were found in the rates of violence
      for the study sample and published data for a community sample of Jordanian
      women. Intimate partner violence is as prevalent against Jordanian nurses as it
      is for Jordanian women. Intimate partner violence needs to be addressed to
      prevent potential sequelae such as decreased work productivity and an inability
      to provide safe patient care. 

PMID- 24434946
TI  - Video gaming and sexual violence: rethinking forensic nursing in a digital age.
AB  - This article reports findings from a qualitative study into how forensic nurses,
      and male personality disordered sexual offenders, talked about "pornography" in
      one U.K. high-security hospital. Research rationale was rooted in current
      professional and political debates, adopting a discourse analytic design to
      situate the project in a clinical context. Semistructured interviews, as co
      constructed accounts, explored talk about sexual media, offending, treatment, and
      risk. Data were analyzed using a version of discourse analysis popular in
      healthcare research, identifying discursive repertoires, or collective language
      use, characteristic of the institutional culture. Findings revealed that
      masculine discourse marginalized female nurses and contradicted therapeutic
      goals, where men's talk about pornography, sex, and sexual crime represented
      discriminatory and gendered language. Nursing definitions of pornography were
      constructed in the context of the client group and an organizational need to
      manage risk. In a highly controlled environment, with a long-stay population,
      priority in respondent talk was given to mainstream commercial sexual media and
      everyday items/images perceived to have embedded sexual meaning. However, little
      mention was made of contemporary modes of producing/distributing pornography,
      where sex and sexual violence are enacted in virtual realities of cyberspace.
      Failure to engage with information technology, and globally mediated sex, is
      discussed as a growing concern for forensic health workers. 

PMID- 24434947
TI  - Molecular imaging in sporadic Alzheimer's disease populations and those
      genetically at risk.
AB  - The time course and order of the pathological-physiological processes in
      Alzheimer's disease (AD) are still under investigation and it is expected that
      molecular imaging will provide important insight into early brain pathology.
      Multi-tracer positron emission tomography studies visualizing fibrillar amyloid,
      inflammatory changes including astrocytosis and activation of microglia as well
      as cerebral glucose metabolism indicate that AD pathological processes are
      initiated and ongoing decades before the onset of cognitive symptoms. Therefore,
      prevention might be a new promising target for AD therapy.

PMID- 24434948
TI  - Early postnatal additional high-dose oral vitamin A supplementation versus
      placebo for 28 days for preventing bronchopulmonary dysplasia or death in
      extremely low birth weight infants.
AB  - BACKGROUND: Prematurity and the associated risk for bronchopulmonary dysplasia
      (BPD) remain a significant threat to extremely low birth weight (ELBW) infants.
      Vitamin A has been considered a therapeutic alternative in reducing the rate of
      BPD and mortality. OBJECTIVES: To investigate whether early postnatal, additional
      high-dose oral vitamin A supplementation for 28 days is more efficient in
      reducing BPD or death in ELBW infants than placebo treatment. METHODS: This is a
      multicenter, double-blind RCT comparing postnatal high-dose oral vitamin A
      supplementation (5,000 IU vitamin A/kg/day vs. placebo) for 28 days in ELBW
      neonates requiring mechanical ventilation, noninvasive ventilatory support or
      supplemental oxygen at 24 h of age. The primary end point is the proportion of
      children who died before 36 weeks' gestational age or developed moderate or
      severe BPD. BPD is defined as the need for supplemental oxygen to maintain SaO2
      of >=92% at rest at 36 weeks' postmenstrual age (PMA). Clinical secondary end
      points include the following: BPD (including mild form), intraventricular
      hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing
      enterocolitis, total number of days of mechanical ventilation and oxygen
      supplementation, and safety and tolerability of high-dose vitamin A
      supplementation. RESULTS AND CONCLUSIONS: The results of the NeoVitaA trial will
      provide robust data with regard to the efficacy of high-dose oral vitamin A
      supplementation in reducing the incidence of BPD or death at 36 weeks' PMA in
      ELBW infants.

PMID- 24434951
TI  - The stress of stigma: exploring the effect of weight stigma on cortisol
      reactivity.
AB  - OBJECTIVE: To determine the physiological impact of exposure to weight stigma by
      examining alterations in salivary cortisol among lean and overweight women.
      METHODS: Participants were 123 lean and overweight adult women (mean body mass
      index = 26.99 [7.91] kg/m(2)). Participants' salivary cortisol was assessed both
      before and after either a weight stigmatizing or a neutral video. Participants
      completed self-report measures of mood and reactions to the video. Height and
      weight were obtained at the conclusion of the study. RESULTS: Participants in the
      stigmatizing condition exhibited significantly greater cortisol reactivity when
      compared with those in the neutral condition, irrespective of weight status
      (Pillai trace = 0.077; F(1,85) = 7.22, p = .009). Lean and overweight women in
      the stigmatizing condition were equally likely to find the video upsetting and
      were equally likely to report that they would rather not see obese individuals
      depicted in a stigmatizing manner in the media. CONCLUSIONS: Exposure to weight
      stigmatizing stimuli was associated with greater cortisol reactivity among lean
      and overweight women. These findings highlight the potentially harmful
      physiological consequences of exposure to weight stigma.

PMID- 24434950
TI  - Association of anxiety disorders and depression with incident heart failure.
AB  - OBJECTIVE: Depression has been associated with increased risk of heart failure
      (HF). Because anxiety is highly comorbid with depression, we sought to establish
      if anxiety, depression, or their co-occurrence is associated with incident HF.
      METHODS: A retrospective cohort (N = 236,079) including Veteran's Administration
      patients (age, 50-80 years) free of cardiovascular disease (CVD) at baseline was
      followed up between 2001 and 2007. Cox proportional hazards models were computed
      to estimate the association between anxiety disorders alone, major depressive
      disorder (MDD) alone, and the combination of anxiety and MDD, with incident HF
      before and after adjusting for sociodemographics, CVD risk factors (Type 2
      diabetes, hypertension, hyperlipidemia, obesity), nicotine dependence/personal
      history of tobacco use, substance use disorders (alcohol and illicit drug
      abuse/dependence), and psychotropic medication. RESULTS: Compared with unaffected
      patients, those with anxiety only, MDD only, and both disorders were at increased
      risk for incident HF in age-adjusted models (hazard ratio [HR] = 1.19 [ 95%
      confidence interval {CI} = 1.10-1.28], HR = 1.21 [95% CI = 1.13-1.28], and HR =
      1.24 [95% CI = 1.17-1.32], respectively). After controlling for psychotropics in
      a full model, the association between anxiety only, MDD only, and both disorders
      and incident HF increased (HRs = 1.46, 1.56, and 1.74, respectively).
      CONCLUSIONS: Anxiety disorders, MDD, and co-occurring anxiety and MDD are
      associated with incident HF in this large cohort of Veteran's Administration
      patients free of CVD at baseline. This risk of HF is greater after accounting for
      protective effects of psychotropic medications. Prospective studies are needed to
      clarify the role of depression and anxiety and their pharmacological treatment in
      the etiology of HF.

PMID- 24434949
TI  - Regulating toxin-antitoxin expression: controlled detonation of intracellular
      molecular timebombs.
AB  - Genes for toxin-antitoxin (TA) complexes are widely disseminated in bacteria,
      including in pathogenic and antibiotic resistant species. The toxins are
      liberated from association with the cognate antitoxins by certain physiological
      triggers to impair vital cellular functions. TAs also are implicated in
      antibiotic persistence, biofilm formation, and bacteriophage resistance. Among
      the ever increasing number of TA modules that have been identified, the most
      numerous are complexes in which both toxin and antitoxin are proteins.
      Transcriptional autoregulation of the operons encoding these complexes is key to
      ensuring balanced TA production and to prevent inadvertent toxin release. Control
      typically is exerted by binding of the antitoxin to regulatory sequences upstream
      of the operons. The toxin protein commonly works as a transcriptional corepressor
      that remodels and stabilizes the antitoxin. However, there are notable exceptions
      to this paradigm. Moreover, it is becoming clear that TA complexes often form one
      strand in an interconnected web of stress responses suggesting that their
      transcriptional regulation may prove to be more intricate than currently
      understood. Furthermore, interference with TA gene transcriptional autoregulation
      holds considerable promise as a novel antibacterial strategy: artificial release
      of the toxin factor using designer drugs is a potential approach to induce
      bacterial suicide from within. 

PMID- 24434952
TI  - Endothelin-1 and psychosocial risk factors for cardiovascular disease: a
      systematic review.
AB  - OBJECTIVES: Psychosocial factors (i.e., social environment and emotional factors)
      contribute to an increased risk of cardiovascular disease (CVD). Perturbation in
      a potent vasoconstrictive peptide endothelin (ET)-1 could be one of the
      mechanisms linking psychosocial factors to CVD. Our aim was to evaluate the
      literature on the relationship between plasma ET-1 and psychosocial risk factors
      for CVD. METHODS: MEDLINE and PsycINFO databases were searched for articles on
      human studies published in peer-reviewed English-language journals through
      September 2012. RESULTS: Of the 20 studies that met the inclusion criteria, 14
      were experimental studies of acute psychological/mental challenges and 6 were
      observational studies of psychological and social factors. The inferences drawn
      from this review were as follows: a) laboratory-induced acute
      psychological/mental stress may result in exaggerated plasma ET-1 release in
      those with CVD and those at risk for CVD (positive studies: 5/10); b)
      chronic/episodic psychosocial factors may have a positive relationship to plasma
      ET-1 (positive studies: 3/5); and c) race (African American), sex (male), and
      individual differences in autonomic and hemodynamic responses to stress
      (parasympathetic withdrawal and elevated blood pressure responsiveness) may
      moderate the relationship between psychosocial factors and plasma ET-1.
      CONCLUSIONS: This review indicates that psychosocial risk factors for CVD are
      associated with elevated plasma ET-1; however, the relatively small number of
      studies, methodological differences, and variable assessment tools preclude
      definitive conclusions about the strength of the association. Specific
      suggestions regarding the selection of psychosocial factors, optimization of
      acute challenge protocols, and standardization of methods and timing of the ET-1
      measures are provided.

PMID- 24434954
TI  - Apolipoprotein E and depressive symptoms: shared or independent routes to age
      related cognitive decline?
AB  - Variation in the apolipoprotein E (APOE) genotype is associated with cognitive
      decline in normal aging. Increased symptoms of depression are also associated
      with greater cognitive impairment and risk of dementia in old age. Unlike APOE,
      where the direction of the effect is from genotype to cognitive decline, the
      causal relationship between depressed mood and cognitive impairment is not known.
      Rather than being a reaction to worsening cognitive performance with age,
      depressive symptoms might be a risk factor for age-related cognitive decline. The
      study by Rajan and colleagues (published in this issue of Psychosomatic Medicine)
      speaks to this possibility and, importantly, considers the association between
      depressive symptoms and age-related cognitive decline in the context of APOE
      variation. This editorial discusses these findings in relation to causal pathways
      and highlights how longitudinal studies of this nature will improve our
      understanding of the biological underpinnings of cognitive decline and
      classification of its risk in the general population. 

PMID- 24434955
TI  - Chromosome 16 abnormalities in embryos and in sperm from a male with a fragile
      site at 16q22.1.
AB  - Two fragile sites, FRA16B and FRA16C, are located in the chromosome band 16q22.1.
      Neither of them is associated with any specific clinical condition. We report the
      development and outcome of a clinically applied PGD cycle in a couple who had
      difficulty in achieving pregnancy. The woman was a carrier of a balanced
      reciprocal translocation, t(11;22)(q23;q11.2), and the man presented high
      expression of the fragile site 16q22.1 (FRA16B/C) in peripheral blood
      lymphocytes. Gains and losses of chromosome 16 fragments were detected in sperm
      and embryos. To our knowledge, this is the first documented case suggesting a
      link between FRA16B/C and chromosome 16 abnormalities in embryos and sperm from a
      carrier.

PMID- 24434953
TI  - Gene-behavior interaction of depressive symptoms and the apolipoprotein E
      {varepsilon}4 allele on cognitive decline.
AB  - OBJECTIVE: Depressive symptoms and the apolipoprotein E (APOE) epsilon4 allele
      are independent risk factors for cognitive decline. However, it is not clear
      whether the presence of both depressive symptoms and the APOE epsilon4 allele
      increases cognitive decline. METHODS: A prospective study of a population-based
      sample of 4150 (70% African American and 63% women) participants 65 years and
      older who were interviewed at 3-year intervals was conducted. Depressive symptoms
      were measured using the 10-item version of the Center for Epidemiologic Studies
      Depression scale, with each item coded as presence or absence of a symptom. The
      APOE genotype was ascertained by DNA samples collected during follow-up.
      Cognitive function was assessed at the initial and follow-up interviews (average
      follow-up of 9.2 years), using a standardized global cognitive score. RESULTS:
      There were 1405 (34%) participants with one or more copies of the APOE epsilon4
      allele. In participants with no depressive symptoms, cognitive function decreased
      by 0.0412 unit per year among those with no copies and 0.0704 unit per year among
      those with one or more copies of the APOE epsilon4 allele. For each additional
      symptom of depression, cognitive decline increased by 0.0021 unit per year among
      those with no copies and 0.0051 unit per year among those with one or more copies
      of the APOE epsilon4 allele. The three-way interaction of depressive symptoms,
      APOE epsilon4 allele, and time was significant (p = .021). CONCLUSIONS: The
      association of depressive symptoms on cognitive decline was increased among
      participants with one or more copies of the APOE epsilon4 allele compared with
      those without the allele.

PMID- 24434956
TI  - Comprehensive meta-analysis of excess mortality in depression in the general
      community versus patients with specific illnesses.
AB  - OBJECTIVE: Several hundred studies have shown that depression is associated with
      an elevated risk of dying at follow-up. It is not clear, however, whether the
      mechanisms for this association are disease specific, leading to higher mortality
      in specific patient groups, or generic, resulting in comparable mortality rates
      in all patient groups as well as in community samples. The authors conducted a
      comprehensive meta-analysis of prospective studies of community as well as
      patient samples associating depression at baseline with excess mortality at
      follow-up. METHOD: The authors conducted systematic searches of PubMed, PsycINFO,
      and Embase. Studies were included if depression was measured with a standardized
      instrument and mortality was reported for both depressed and nondepressed
      participants at follow-up. RESULTS: A total of 293 studies including 1,813,733
      participants (135,007 depressed and 1,678,726 nondepressed) from 35 countries
      were included. The overall unadjusted relative risk of mortality in depressed
      relative to nondepressed participants was 1.64 (95% CI=1.56-1.76), with high
      heterogeneity (I2=83, 95% CI=80-84). After adjustment for publication bias, the
      overall relative risk was reduced to 1.52 (95% CI=1.45-1.59). No strong
      indications were found that the pooled relative risk was different across the
      relatively healthy community samples and specific patient samples with heart
      disease, cancer, kidney disease, or other disease, except for a significantly
      higher risk in patients with chronic obstructive pulmonary disease (p<0.05).
      Also, the relative risk was lower when the follow-up period was longer and when
      the quality of the study was higher. CONCLUSIONS: The authors could confirm the
      presence of a significant association between depression and excess mortality,
      although this association may have been overestimated because of publication bias
      and low study quality. Few indications were found that this association is
      stronger in community or specific patient samples.

PMID- 24434957
TI  - Catalytic hydroacetylenation of carbodiimides with homoleptic alkaline earth
      hexamethyldisilazides.
AB  - The homoleptic alkaline earth hexamethyldisilazides, [M{N(SiMe3)2}2(THF)2] (M =
      Mg 1a; Ca 1b; Sr 1c), have been shown to act as efficient precatalysts for the
      hydroacetylenation of organic carbodiimides with alkyl- and arylacetylenes.
      Catalytic activity was observed to increase with the size of the group 2 metal
      centre employed and to be strongly influenced by the steric properties of the
      carbodiimide substrate. The intermediate dimeric calcium and strontium
      bis(amidinate) complexes, [{PhC=CC(N(i)Pr)2}2M]2 (M = Ca 2b, Sr 2c), have been
      isolated and crystallographically characterised. Kinetic studies using the
      strontium precursor, 1c, provided a reaction rate law independent of [acetylene]
      but proportional to [carbodiimide](2) and inversely proportional to the
      concentration of the amidine product in solution.

PMID- 24434958
TI  - [Medication-based therapy of infantile hemangioma and lymphatic malformations].
AB  - The therapy of vascular tumors and malformations should be interdisciplinary and
      performed according to available guidelines. Infantile hemangiomas (IH) are the
      most frequent vascular tumors of childhood and do not require treatment in most
      cases. If the IH is complicated by its location (e.g. facial or genital) or if
      the lesion threatens to cause loss of function, small localized IH should be
      treated by laser- or cryotherapy. If the IH is diffuse or rapidly growing it can
      be successfully treated using the beta blocker propranolol. The mechanism
      underlying the efficacy of this medication-based therapy is not completely
      understood and this still represents an experimental therapy. The results of
      molecular studies on vascular malformations have indicated new strategies for
      medical therapies. However, lymphatic malformations (LM) are still treated by
      surgery where possible, or sclerotherapy. Further investigations are necessary to
      determine whether new drugs such as the mTOR inhibitor rapamycin may be effective
      for treatment of diffuse LM. First case reports seem to be promising. 

PMID- 24434959
TI  - [Contribution to the discussion surrounding the Freiburg speech test].

PMID- 24434961
TI  - Metabolic profiling of biofilm bacteria known to cause microbial influenced
      corrosion.
AB  - This study builds upon previous research that demonstrated the simplicity of
      obtaining metabolite profiles of bacteria in urban water networks, by using the
      metabolic profile of bacteria extracted from a reticulation pipe biofilm, which
      is known to cause microbial influenced corrosion (MIC). The extracellular
      metabolites of the isolated bacteria, and those bacteria in consortium, were
      analysed in isolation, and after exposure to low levels of copper. Applying
      chemometric analytical methodologies to the metabolomic data, we were able to
      better understand the profile of the isolated biofilm bacteria, which were
      differentiated according to their activity and copper exposure. It was found that
      the metabolic activity of the isolated bacteria and the bacteria in consortium
      varied according to the bacterium's ability to metabolise copper. This
      demonstrates the power of metabolomic techniques for the discrimination of water
      reticulation biofilms comprising similar bacteria in consortium, but undergoing
      different physico-chemical activities, such as corrosion and corrosion
      inhibition. 

PMID- 24434960
TI  - Insulin pump use in pregnancy is associated with lower HbA1c without increasing
      the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to compare glycaemic control and
      maternal-fetal outcomes in women with type 1 diabetes managed on insulin pumps
      compared with multiple daily injections of insulin (MDI). METHODS: In a
      retrospective study, glycaemic control and outcomes of 387 consecutive
      pregnancies in women with type 1 diabetes who attended specialised clinics at
      three centres 2006-2010 were assessed. RESULTS: Women using insulin pumps
      (129/387) were older and had a longer duration of diabetes, more retinopathy,
      smoked less in pregnancy, and had more preconception care (p < 0.01 for each).
      Among 113 pregnancies >20 weeks' gestation in women on insulin pumps and 218 in
      women on MDI, there was a significant difference in HbA1c in the first trimester
      (mean HbA1c 6.90 +/- 0.71% (52 +/- 7.8 mmol/mol) vs 7.60 +/- 1.38% (60 +/- 15.1
      mmol/mol), p < 0.001), which persisted until the third trimester (mean HbA1c 6.49
      +/- 0.52% (47 +/- 5.7 mmol/mol) vs 6.81 +/- 0.85% (51 +/- 9.3 mmol/mol), p =
      0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs
      MDI (1.8% vs 3.0%, p = 0.72). Despite lower HbA1c, women on insulin pumps did not
      have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p = 0.90) or
      more weight gain (16.3 +/- 8.7 vs 15.2 +/- 6.2 kg, p = 0.18). More large-for
      gestational-age infants in the pump group (55.0% vs 39.2%, p = 0.007) may have
      resulted from confounding by parity. CONCLUSIONS/INTERPRETATION: In this large
      multicentre study, women using insulin pumps in pregnancy had lower HbA1c without
      increased risk of severe hypoglycaemia or diabetic ketoacidosis but no
      improvement in other pregnancy outcomes. This information can help inform care
      providers and patients about the glycaemic effectiveness and safety of insulin
      pumps in pregnancy.

PMID- 24434962
TI  - Performance evaluation and bacteria analysis of AFB-MFC enriched with high
      strength synthetic wastewater.
AB  - In order to study the performance and bacterial communities of an anaerobic
      fluidized bed microbial fuel cell (AFB-MFC) system, the 16S rDNA gene sequencing
      was applied, and high-strength synthetic wastewater was treated by the AFB-MFC
      system. The high-strength synthetic wastewater, in which the concentrations of
      chemical oxygen demand (COD), nitrite nitrogen, and nitrate nitrogen were above
      19,000, 2,516-3,871 and 927-1,427 mg/L, was treated by the AFB-MFC system. The
      removal efficiency of COD, nitrite nitrogen, and nitrate nitrogen reached 70-89,
      98 and 98%, while the maximum voltage was 394 mV. The bacteria analysis revealed
      the presence of Alistipes putredinis, Carnobacterium sp., Victivallis vadensis,
      Klebsiella pneumoniae, Thauera sp., Parabacteroides merdae, Parvimonas micra,
      Parabacteroides sp., and Desulfomicrobium baculatum in the anode chamber. In
      addition, the Klebsiella pneumoniae was observed to have the capability of
      organic degradation and electricity generation, while the Thauera sp. has the
      capability of denitrification. 

PMID- 24434963
TI  - Effect of ambient temperatures on disinfection efficiency of various sludge
      treatment technologies.
AB  - Sewage sludge produced during municipal wastewater treatment has to be treated
      efficiently in order to reduce impacts on the environment and on public health.
      In Germany and many countries, large quantities of sludge are reused in
      agriculture in order to recycle nutrients and organic material. In order to
      quantify the effect of different ambient temperatures on conventional and
      advanced sludge treatment technologies as well as on disinfection efficiency, a
      comprehensive research study was performed at Braunschweig Institute of
      Technology. The detailed results show that ambient temperature has a strong
      effect on biological liquid sludge stabilization and on natural dewatering and
      drying technologies, although microbiological quality of treated sludge,
      indicated by Escherichia coli concentration, does not meet the requirements for
      unrestricted reuse in agriculture. Composting and lime treatment of sludge are
      most efficient on reducing E. coli, as high temperatures and high pH values arise
      in the material respectively. 

PMID- 24434964
TI  - Separation of solids and disinfection for agronomical use of the effluent from a
      UASB reactor.
AB  - The present work addresses the preparation of the effluent from a full-scale
      upflow anaerobic sludge blanket (UASB) reactor for drip irrigation of orange
      crops. The pilot plant included a lamella plate clarifier followed by a geo
      textile blanket filter and a UV disinfection reactor. The clarifier operated with
      a surface load of 115 m(3)m(-2)d(-1), whereas the filter operated with 10 m(3)m(
      2)d(-1). The UV reactor was an open-channel type and the effective dose was
      approximately 2.8 W h m(-3). The effluent of the UASB reactor received 0.5 mg L(
      1) cationic polyelectrolyte before entering the high-rate clarifier. Suspended
      solids' concentrations and Escherichia coli and helminth egg's densities were
      monitored throughout the treatment system for 12 months. Results showed that the
      total suspended solids concentration in the filter effluent was lower than 7 mg
      L(-1) and helminth density was below 1.0 egg L(-1). The UV disinfection
      demonstrated the ability to produce a final effluent with E. coli density lower
      than 10(3)MPN/100 mL (MPN: most probable number) during the entire process. Thus,
      the World Health Organization standards for unrestricted crop use were met.
      Agronomic interest parameters were controlled and it was possible to identify the
      important contribution of treated sewage in terms of the main nutrients. 

PMID- 24434965
TI  - Characterizing o- and p-nitrophenols adsorption onto innovative activated carbon
      prepared from date pits.
AB  - The production and performance of activated carbon prepared from date pits was
      investigated. Date pits are an abundant local waste product in many countries;
      converting them to a commercial product would increase the sustainability of this
      fruit crop. The date pit activated carbon was shown to have similar
      characteristics of pore size and surface functional groups as other commercial
      carbons. Batch experiments were conducted with o- and p-nitrophenol to evaluate
      the performance of this carbon. Results were analyzed according to Langmuir,
      Freundlich, and Dubinin-Radushkevich adsorption isotherms. The adsorption
      capacity of o-nitrophenol was 142.9 mg/g while that of p-nitrophenol was 108.7
      mg/g. The adsorption process was physical in nature. The position of the -NO(2)
      group in the benzene ring has a considerable effect on the adsorption capacity
      and rate of uptake. The kinetic results showed that a pseudo second-order model
      appropriately describes the experimental data. The analysis of kinetic data
      revealed that the mechanism of adsorption is complex with both liquid film
      diffusion and intraparticle diffusion contributing to adsorption of both
      adsorbates.

PMID- 24434966
TI  - Treatment of municipal wastewater using horizontal flow constructed wetlands in
      Egypt.
AB  - The aim of this study was to evaluate the performance of two pilot horizontal
      flow constructed wetlands (HFCWs) with and without vegetation. Three types of
      plants namely Canna, Phragmites australis and Cyprus papyrus were used. The
      surface area of each plant was 654 m(2). The flow rate was 20 m(3) d(-1) and the
      organic loading rate range was 1.7-3.4 kg BOD d(-1) with a detention time of 11
      days. The results obtained showed that planted HFCW produced high quality
      effluent in terms of reduction of chemical oxygen demand (COD; 88%), biochemical
      oxygen demand (BOD; 91%) and total suspended solids (TSS; 92%) as well as
      nutrient removal. In addition, 4 logs of total coliform were removed from the
      planted unit compared with only 3 logs in the unplanted one. The phosphate uptake
      by the plants reached 29, 30.91 and 38.9 g P m(-2) for Canna, Phragmites and
      Cyprus, respectively, with 60% removal rate in the treated effluent. The nitrogen
      uptake by the same plants reached 63.1, 49.46 and 82.33 g N m(-2). Although, the
      unplanted unit proved to be efficient in the removal of COD, BOD and TSS, it
      lacks efficiency in pathogen and nutrient removal. The reclaimed wastewater,
      after disinfection, could be reused for non-restricted irrigation purposes. 

PMID- 24434967
TI  - A molecular imprinted polymer based sensor for measuring phosphate in wastewater
      samples.
AB  - Phosphate detection in water samples is still completed using colorimetric
      standard methods, which have a number of disadvantages, to such as being time
      consuming, requiring filtration, a number of different reagents, frequent
      calibration and proper disposal of waste chemicals generated. Hence, a simple
      cost effective analytical method and instrumentation is highly desirable to aid
      the optimisation of treatment processes and assist the water industry in their
      efforts to comply with stringent regulations such as the EU's Water Framework
      Directive. A sensor based on molecular imprinted polymer (MIP) and a conductance
      transducer was developed for direct and label-free detection of phosphate in
      water. The sensor was able to measure the presence of phosphate in wastewater
      samples with good reproducibility, a linear range of 0.66-8 mg P L(-1) and a
      lower detection limit of 0.16 mg P L(-1). The sensor was further tested to
      measure phosphate concentrations in unfiltered field samples such as domestic
      wastewater treatment influent and river water and demonstrated a close
      correlation with reference measurements. The phosphate MIP sensor offers a way
      forward as either a handheld sensor for use in the field, or as a potential
      solution for remote, continuous monitoring of phosphate. 

PMID- 24434968
TI  - Organic removal activity in biofilm and suspended biomass fractions of MBBR
      systems.
AB  - The moving bed biofilm reactor (MBBR) wastewater treatment process is usually
      designed based on the assumption that all activity in the process occurs in the
      biofilm on the MBBR carriers, although there is always some active biomass in the
      bulk liquid due to biofilm sloughing and, sometimes, free-growing bacteria. In
      this study the removal of organic matter is evaluated in laboratory-scale MBBR
      reactors under varying load, hydraulic retention time (HRT), oxygen concentration
      and volumetric filling degree of carriers in order to determine the heterotrophic
      activity in the different fractions of the MBBR biomass. The results showed that
      the heterotrophic conversions in an MBBR can show the same type of diffusion
      limited dependency on oxygen as nitrification, even for easily degradable
      substrates such as acetate. The contribution to the removal from the suspended
      biomass is shown to vary depending on HRT, as the amount of suspended solids
      changes. The developed method in this report is a useful tool for determining
      heterotrophic activity in the separate fractions of biomass in MBBRs. 

PMID- 24434969
TI  - Development of a highly specific and productive process for n-caproic acid
      production: applying lessons from methanogenic microbiomes.
AB  - High productivity and specificity in anaerobic digesters arise because complex
      microbiomes organize into a metabolic cascade to maximize energy recovery and to
      utilize the advantage that the gaseous end product methane freely bubbles out of
      the system. These lessons were applied to ascertain whether a reactor microbiome
      could be shaped to produce a different end product. The liquid product n-caproic
      acid was chosen, which is a 6-carbon-chain carboxylic acid that is valuable and
      that has a relatively low maximum solubility concentration for product recovery.
      Acetoclastic methanogenesis was inhibited by pH control and a route was provided
      for n-caproic acid extraction by implementing selective, in-line recovery. Next,
      ethanol was supplemented to promote chain elongation, which is a pathway in which
      short-chain carboxylic acids are elongated sequentially into medium-chain
      carboxylic acids with two-carbon units derived from ethanol. The reactor
      microbiome developed accordingly with the terminal process catalyzed by chain
      elongating bacteria. As a result, n-caproic acid production rates increased to
      levels comparable to anaerobic digestion systems for solid waste treatment. 

PMID- 24434970
TI  - Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofuran concentrations
      in Xingyun Lake sediment close to the pulp mill region of Jiangchuan (China): a
      typical case study.
AB  - Sediment cores from Xingyun Lake close to the pulp mill region of Jiangchuan
      (China), earlier found to be highly contaminated by pulping at least from the
      1990s, were analyzed by HRGC/HRMS for the concentrations of 17 polychlorinated
      dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs). Regarding the
      contribution of individual congeners, PCDD/F levels ranged from ND (non
      detectable) to 82.05 pg g(-1) dw (from ND to 0.16 pg WHO-TEQ g(-1) dw) in 0-20 cm
      of sediment and from ND to 45.61 pg g(-1) dw (from ND to 0.67 WHO-TEQ g(-1) dw)
      in 20-40 cm of sediment for 17 PCDD/Fs (WHO-TEQ: WHO-endorsed toxic equivalents).
      Major PCDD/Fs identified and confirmed were high-chlorinated congeners including
      OCDD/Fs and HpCDD/Fs in the two depths. For high-chlorinated PCDD/Fs such as O,
      Hp-CDD/Fs across the depth of sediment, sediment had a higher proportion in 0-20
      cm than that in 20-40 cm. On the contrary, for low-chlorinated PCDD/Fs such as T,
      Pe, Hx-CDD/Fs, the lower proportion was found in 0-20 cm. The results
      demonstrated that PCDD/Fs loads in the sediment of Xingyun Lake were very low
      compared to loads in the other regions about 8 years after closedown of a
      majority of pulp production with chlorine, which indicated that pulp production
      was an important emission source of dioxins. 

PMID- 24434971
TI  - Dielectric barrier discharge induced degradation of diclofenac in aqueous
      solution.
AB  - A dielectric barrier discharge (DBD) reactor as one of the advanced oxidation
      processes was applied to the degradation of diclofenac in aqueous solution. The
      various parameters that affect the degradation of diclofenac and the proposed
      evolutionary process were investigated. The results indicated that the inner
      concentrations of 10 mg/L diclofenac can be all removed within 10 min under
      conditions of 50 W and pH value of 6.15. The existence of Fe(2+) in the liquid
      phase can promote the degradation of diclofenac. But it was rather ineffective in
      mineralization, because the intermediates containing the aromatic rings were
      recalcitrant to be degraded. Five intermediates were identified by liquid
      chromatography-mass spectrometry (LC-MS), the OH . radical and O(3) were the
      major reactive species, and played an important role in the degradation of
      diclofenac. The toxicity of diclofenac degraded by DBD was assessed and the
      results indicated the efficiency of the DBD in the detoxification of the
      diclofenac solution.

PMID- 24434972
TI  - Oxygen-induced dynamics of nitrous oxide in water and off-gas during the
      treatment of digester supernatant.
AB  - Nitrous oxide (N(2)O) is a potent greenhouse gas and of special concern in
      wastewater treatment. It is formed in biological wastewater treatment under both
      aerobic and anaerobic conditions. A major reason for high N(2)O emissions is low
      oxygen concentration during nitrification. In this full-scale study of N(2)O
      emissions from a sequencing batch reactor for treating digester supernatant, the
      oxygen concentration was reduced stepwise to investigate how N(2)O emissions were
      influenced. N(2)O concentrations were measured online in water and off-gas. A
      distinct relationship was found between low oxygen concentration and high N(2)O
      emissions. N(2)O was formed in water during both nitrification and
      denitrification. Decreased oxygen concentration during nitrification led to
      increased nitrite concentration, which in turn led to increased N(2)O
      concentration in the subsequent denitrification phase. When the nitrification
      resumed, accumulated N(2)O was stripped off to the atmosphere. Very high
      concentrations of N(2)O, over 56,000 ppmv, were measured in the off-gas.
      Furthermore, the maximum amount of N(2)O emitted during one cycle corresponded to
      107.6% of the total nitrogen load (21.9% of total nitrogen present in the bulk
      liquid at the beginning of the cycle). This is among the highest emission levels
      ever measured from a full-scale municipal plant for digester supernatant.

PMID- 24434973
TI  - Is H2S a suitable process indicator for odour abatement performance of sewer
      odours?
AB  - Odour abatement units are typically designed and maintained on H(2)S
      concentrations, but operational failures are reported in terms of overall odour
      removal, suggesting a wide range of malodorous compounds emitted from sewers that
      may not be efficiently removed by existing odour abatement processes. Towards
      providing greater insight into this issue, several activated carbon filters and
      biofilters treating odorous emissions from sewer systems in Sydney (Australia)
      were monitored by collecting and analysing gas samples before and after
      treatment. The monitoring studies were conducted by both olfactometric
      measurements and gas-chromatography-based chemical analysis. Single H(2)S
      assessment often failed to indicate the odour abatement performance for treatment
      systems in the abatement units studied, particularly when the incoming H(2)S
      concentrations were in the sub-ppm range (i.e. below H(2)S odour threshold).
      Chemical analysis indicated that some non-H(2)S odorous compounds were not
      removed efficiently during odour treatment. Additionally, when odour eliminations
      were correlated with the removal of individual compounds (Pearson's correlations)
      it was observed that the correlation (with a coefficient of 0.79) was best when
      the overall removal of all the measured odorous compounds that exceeded their
      odour threshold values was used for the analysis. These findings may help to
      further advance the design and operation of odour abatement processes to address
      the treatment of sewer odour emissions.

PMID- 24434974
TI  - Assessment of the effects of greywater reuse on gross solids movement in sewer
      systems.
AB  - Onsite greywater reuse (GWR) and installation of water-efficient toilets (WETs)
      reduce urban freshwater demand and thus enhance urban water use sustainability.
      Research on GWR and WETs has generally overlooked their potential effects on
      municipal sewer systems: GWR and WETs affect the flow regime in sewers, and
      consequently also influence gross solids transport. To asses these impacts, a
      gross solids transport model was developed. The model is based on approaches
      found in the literature. Hydrodynamic calculations of sewage flow were performed
      using the SIMBA6 simulator and then used for the gross solid movement models.
      Flow characteristics in the up- and downstream sections of the sewer network
      differ. Therefore different approaches were used to model solids movement in each
      of these two parts. Each model determines whether a solid moves as a result of a
      momentary sewage flow, and if it moves, calculation of its velocity is possible.
      The paper shows the adoption and implementation of two gross solids transport
      models using SIMBA6 and depicts the results of the effects of various GWR and WET
      scenarios on gross solids movement in sewers for a real case study in Israel. 

PMID- 24434975
TI  - French vertical flow constructed wetlands: a need of a better understanding of
      the role of the deposit layer.
AB  - French vertical flow constructed wetlands, treating directly raw wastewater, have
      become the main systems implemented for communities under 2,000 population
      equivalent in France. Like in sludge drying reed beds, an organic deposit layer
      is formed over time at the top surface of the filter. This deposit layer is a key
      factor in the performance of the system as it impacts hydraulic, gas transfers,
      filtration efficiency and water retention time. The paper discusses the role of
      this deposit layer on the hydraulic and biological behaviour of the system. It
      presents results from different studies to highlight the positive role of the
      layer but, as well, the difficulties in modelling this organic layer. As
      hydraulic, oxygen transfers, and biological activity are interlinked and impacted
      by the deposit layer, it seems essential to focus on its role (and its
      quantification) to find new developments of vertical flow constructed wetlands
      fed with raw wastewater. 

PMID- 24434976
TI  - Enhanced photocatalytic activity of CeO2 using beta-cyclodextrin on visible light
      assisted decoloration of methylene blue.
AB  - An attempt has been made to enhance the photocatalytic activity of CeO(2) for
      visible light assisted decoloration of methylene blue (MB) dye in aqueous
      solutions by beta-cyclodextrin (beta-CD). The inclusion complexation patterns
      between host and guest (i.e., beta-CD and MB) have been confirmed with UV-visible
      spectral data. The interaction between CeO(2) and beta-CD has also been
      characterized by field emission scanning electron microscopy analysis. The
      photocatalytic activity of the catalyst under visible light was investigated by
      measuring the photodegradation of MB in aqueous solution. The effects of key
      operational parameters such as initial dye concentration, initial pH, CeO(2)
      concentration as well as illumination time on the decolorization extents were
      investigated. Among the processing parameters, the pH of the reaction solution
      played an important role in tuning the photocatalytic activity of CeO(2). The
      maximum photodecoloration rate was achieved at basic pH (pH 11). Under the
      optimum operational conditions, approximately 99.6% dye removal was achieved
      within 120 min. The observed results indicate that the decolorization of the MB
      followed a pseudo-first order kinetics.

PMID- 24434977
TI  - Acclimation of the trichloroethylene-degrading anaerobic granular sludge and the
      degradation characteristics in an upflow anaerobic sludge blanket reactor.
AB  - The granulation process was examined in an 8 L laboratory upflow anaerobic sludge
      blanket (UASB) reactor using synthetic wastewater contained trichloroethylene
      (TCE). Glucose and lactate were used as primary substrates. The anaerobic
      bacteria biomass were acclimated and granulated by increasing the chemical oxygen
      demand (COD) and TCE loadings. Anaerobic sludge was acclimated successfully in
      120 days in the anaerobic sludge acclimation appliance. Since start-up, the UASB
      was operated as a continuous-flow reactor under the following operation
      conditions: temperature of (35 +/- 1) degrees C, pH ~ 7.2, hydraulic retention
      time of 10 h, COD of 2.5 g L(-1) and TCE loading rate from 50.5 to 252.3 mg . (L
      d)(-1). The UASB reactor was started successfully. The sludge volume index was 13
      mL g(-1). The maximum specific methanogenic activity was 1.42 gCOD . (gVSS(.)d)(
      1). After 90 days, 85% of COD and 85% of TCE removal efficiencies were achieved.
      The TCE degrading granular sludge had an average diameter of 2.7 mm and total
      suspended solid of 52 g L(-1). Anaerobic sludge adsorption of TCE reached
      adsorption equilibrium in 0.5 h, and in 1 h reached desorption equilibrium.
      Furthermore, cis-dichloroethylene and vinyl chloride were detected, which showed
      that the removal of TCE was caused by both adsorption and biodegradation but
      mainly by biodegradation. 

PMID- 24434978
TI  - Toluene in sewage and sludge in wastewater treatment plants.
AB  - Toluene is a compound that often occurs in municipal wastewater ranging from
      detectable levels up to 237 MUg/L. Before the year 2000, the presence of the
      aromatic hydrocarbons was assigned only to external sources. The Enhanced
      Biological Nutrients Removal Processes (EBNRP) work according to many different
      schemes and technologies. For high-efficiency biological denitrification and
      dephosphatation processes, the presence of volatile fatty acids (VFAs) in sewage
      is required. VFAs are the main product of organic matter hydrolysis from sewage
      sludge. However, no attention has been given to other products of the process. It
      has been found that in parallel to VFA production, toluene formation occurred.
      The formation of toluene in municipal anaerobic sludge digestion processes was
      investigated. Experiments were performed on a laboratory scale using sludge from
      primary and secondary settling tanks of municipal treatment plants. The
      concentration of toluene in the digested sludge from primary settling tanks was
      found to be about 42,000 MUg/L. The digested sludge supernatant liquor returned
      to the biological dephosphatation and denitrification processes for sewage
      enrichment can contain up to 16,500 MUg/L of toluene. 

PMID- 24434979
TI  - The need for electronic noses for environmental odour exposure assessment.
AB  - This paper focuses on the opportunities for using electronic noses for odour
      exposure assessment purposes, especially in cases where dispersion modelling is
      not applicable. Such cases include, for instance, those sources where a detailed
      characterisation and quantification of the odour emissions for every hour of the
      simulation time domain is particularly difficult, due to the nature of the source
      or to the variability of the emissions over time. In such situations, it is
      useful to determine odour exposure directly at receptors instead. This paper
      critically discusses the state of the art of electronic nose technology as far as
      its application to the determination of odour exposure at receptors is concerned.
      One example of electronic nose application to the monitoring of odours from an
      Italian municipal solid waste (MSW) landfill is reported, in order to discuss the
      instrument's potential and limits. The monitoring results are represented by the
      number of measures that are classified in a specific olfactory class; this
      information allows the odour exposure at each monitoring site in terms of odour
      detection frequency to be determined. Besides a quantification of the odour
      episodes, electronic noses allowed the identification of the landfill gas as the
      monitored landfill major odour source. 

PMID- 24434980
TI  - Comparison of two standard odor intensity evaluation methods for odor problems in
      air or water.
AB  - Government agencies responsible for ensuring healthful water and/or air quality
      are often faced with resolving public complaints of nuisance odors. Understanding
      variations in odor intensity may ultimately lead to the establishment and
      application by such agencies of quantitative limits for effective odorant
      control. An odor panel was trained in suprathreshold odor intensity evaluation
      using both the ASTM Method E544 (Butanol Method) and the APHA Method 2170 (Flavor
      Profile Analysis (FPA) Method). A linear mixed model was fitted to the panel
      data, taking into account the fixed effects of concentration levels and the
      random effects of panelists and sessions. The FPA method proved easier to
      administer and revealed less inter-session variance than the ASTM Method,
      suggesting its greater utility in applications involving odor panels. For both
      methods, there was a high standard deviation, relative to the mean. This finding
      indicates that the intensity scales may be useful for understanding relative odor
      intensities, but should not be used as a precise measure, or as a basis for
      establishing regulatory limits. 

PMID- 24434981
TI  - Magnetic Fe3O4@C nanoparticles as adsorbents for removal of amoxicillin from
      aqueous solution.
AB  - In the present study, powder activated carbon (PAC) combined with Fe(3)O(4)
      magnetite nanoparticles (MNPs) were used for the preparation of magnetic
      composites (MNPs-PAC), which was used as an adsorbent for amoxicillin (AMX)
      removal. The properties of magnetic activated carbon were characterized by
      scanning electron microscopy, transmission electron microscopy, X-ray
      diffraction, Brunaeur, Emmett and Teller and vibrating sample magnetometer. The
      operational factors affecting adsorption such as pH, contact time, adsorbent
      dosage, initial AMX concentration and temperature were studied in detail. The
      high surface area and saturation magnetization for the synthesized adsorbent were
      found to be 671.2 m(2)/g and 6.94 emu/g, respectively. The equilibrium time of
      the adsorption process was 90 min. Studies of adsorption equilibrium and kinetic
      models revealed that the adsorption of AMX onto MNPs-PAC followed Freundlich and
      Langmuir isotherms and pseudo-second-order kinetic models. The calculated values
      of the thermodynamic parameters, such as DeltaG degrees , DeltaH degrees  and
      DeltaS degrees  demonstrated that the AMX adsorption was endothermic and
      spontaneous in nature. It could be concluded that MNPs-PAC have a great potential
      for antibiotic removal from aquatic media.

PMID- 24434982
TI  - Reduction of organic trace compounds and fresh water consumption by recovery of
      advanced oxidation processes treated industrial wastewater.
AB  - Ozone (O(3)) has been used successfully in advanced wastewater treatment in paper
      mills, other sectors and municipalities. To solve the water problems of regions
      lacking fresh water, wastewater treated by advanced oxidation processes (AOPs)
      can substitute fresh water in highly water-consuming industries. Results of this
      study have shown that paper strength properties are not impaired and whiteness is
      slightly impaired only when reusing paper mill wastewater. Furthermore, organic
      trace compounds are becoming an issue in the German paper industry. The results
      of this study have shown that AOPs are capable of improving wastewater quality by
      reducing organic load, colour and organic trace compounds.

PMID- 24434983
TI  - Studies of Pb2+ adsorption by Moringa oleifera Lam. seeds from an aqueous medium
      in a batch system.
AB  - The efficiency of Moringa (Moringa oleifera Lam.) seeds for removing lead ions
      (Pb(2+)) from water was evaluated. Parameters such as solution pH, adsorbent
      mass, contact time between solution and adsorbent, isotherms, thermodynamic,
      kinetics, and desorption were evaluated. The maximum adsorption capacity of the
      biosorbent was found to be 12.24 mg g(-1). In order to verify the effectiveness
      of this material, comparative studies were performed with activated carbon under
      the same optimal conditions for the construction of isotherms and the desorption
      process. Average desorption rate values led to the assumption that a strong
      interaction took place between the adsorbents and the metal ions. Thus, it has
      been concluded that the biosorbent studied herein can be considered very
      effective and feasible for remediating Pb(2+)-contaminated solutions, since this
      material is itself an untreated and low-cost byproduct. 

PMID- 24434984
TI  - Preferential catalytic ozonation of p-nitrophenol by molecularly imprinted
      Fe3O4/SiO2 core-shell magnetic composites.
AB  - Molecularly imprinted Fe(3)O(4)/SiO(2) core-shell magnetic composites
      (Fe(3)O(4)/SiO(2)-MIP) were successfully prepared via anchoring p-nitrophenol (p
      NP) imprinted functional polymers on the surface of amino-modified
      Fe(3)O(4)/SiO(2) core-shell particles. Synthesized magnetic Fe(3)O(4)/SiO(2)-MIP
      composites were characterized by X-ray diffraction, scanning electronic
      microscopy, transmission electron microscopy, Fourier transform infrared
      spectroscopy, and magnetic property measurement. The preferential catalytic
      ozonation of p-nitrophenol was evaluated in comparison with the competitive
      reaction in the presence of coexistent phenol. The results showed that the
      prepared Fe(3)O(4)/SiO(2)-MIP composites exhibit strong adsorption ability due to
      the strong bonding between p-NP and the molecularly imprinted layer. The
      Fe(3)O(4)/SiO(2)-MIP demonstrated a preferential catalytic ozonation of p-NP by
      the recognition ability of the molecularly imprinted layer to the target p-NP.
      The enhanced catalytic activity using Fe(3)O(4)/SiO(2)-MIP composites could be
      attributed to the excellent recognition absorption of the MIP layer on the
      surface of Fe(3)O(4)/SiO(2)-MIP to p-NP.

PMID- 24434985
TI  - Polyhydroxyalkanoate (PHA) production from sludge and municipal wastewater
      treatment.
AB  - Polyhydroxyalkanoates (PHAs) are biodegradable polyesters with comparable
      properties to some petroleum-based polyolefins. PHA production can be achieved in
      open, mixed microbial cultures and thereby coupled to wastewater and solid
      residual treatment. In this context, waste organic matter is utilised as a carbon
      source in activated sludge biological treatment for biopolymer synthesis. Within
      the EU project Routes, the feasibility of PHA production has been evaluated in
      processes for sludge treatment and volatile fatty acid (VFA) production and
      municipal wastewater treatment. This PHA production process is being investigated
      in four units: (i) wastewater treatment with enrichment and production of a
      functional biomass sustaining PHA storage capacity, (ii) acidogenic fermentation
      of sludge for VFA production, (iii) PHA accumulation from VFA-rich streams, and
      (iv) PHA recovery and characterisation. Laboratory- and pilot-scale studies
      demonstrated the feasibility of municipal wastewater and solid waste treatment
      alongside production of PHA-rich biomass. The PHA storage capacity of biomass
      selected under feast-famine with municipal wastewater has been increased up to
      34% (g PHA g VSS(-1)) in batch accumulations with acetate during 20 h. VFAs
      obtained from waste activated sludge fermentation were found to be a suitable
      feedstock for PHA production. 

PMID- 24434986
TI  - Perfluorooctanoate and perfluorooctane sulfonate in South African river water.
AB  - This study examined the prevalence of perfluorooctanoate (PFOA) and
      perfluorooctane sulfonate (PFOS) in river water samples (n = 56) and suspended
      solids (n = 5) from three major Western Cape rivers, in South Africa. Solid phase
      extraction (SPE) followed by liquid chromatography combined with electrospray
      tandem mass spectrometry (LC-MS/MS) using an analytical method developed in ISO
      25101 (2009), PFOS and PFOA concentration in river water and in suspended solids
      from the rivers was investigated and quantified. From the results, PFOA and PFOS
      were detected in all the river water samples and were found in concentrations up
      to 314 and 182 ng/L for Diep River; 390 and 47 ng/L for Salt River; and 146 and
      23 ng/L for Eerste River, respectively. In suspended solids, concentrations for
      PFOS and PFOA were 28 and 26 ng/g for Diep River; 16 and less than limit of
      detection for Eerste River; and 14 and 5 ng/g for Salt River, respectively. Some
      of these concentrations are higher than those previously reported in similar
      studies in various countries, and this suggests there is a cause for concern, in
      the Western Cape, South Africa, particularly in catchments where river and ground
      water is drawn for agricultural purposes in the province. 

PMID- 24434987
TI  - Kinetic evaluation of chromium(VI) sorption by water lettuce (Pistia).
AB  - An investigation was performed to evaluate the uptake capacity of Pistia in
      living condition for adsorptive removal of chromium(VI) from spiked solution for
      examining a remedial measure for disposal of chrome-laden wastewater in an urban
      wetland system. Kinetics results show about 78% removal was achieved for 3 mg/L
      initial concentration of Cr(VI). Experimental data showed that the root portion
      absorbed more Cr(VI) (28.54 MUg/g) compared to accumulation in leaf (5.73 MUg/g).
      It was also noted that the plant could effectively remove Cr(VI) from the
      solution with minor damage up to an initial Cr(VI) concentration of 3 mg/L, for
      which the adsorption isotherm studies were conducted. The maximum uptake capacity
      of the plant was recorded as 0.05 mg/g of Cr(VI) at the equilibrium level after a
      contact period of 7 days for an initial concentration of 8 mg /L, although severe
      physiological damage occurred. The experimental results were plotted in Langmuir
      and Freundlich isotherm models and both were found to be well fitted (r(2) =
      0.979 and r(2) = 0.974 respectively). The high value of n (2.16) reveals a strong
      bond between the plant root and dissolved Cr(VI), which favours the adsorption
      process. The order of the reaction was also examined on the basis of uptake
      capacity and it was found that the second order model fitted best. 

PMID- 24434988
TI  - Membrane filtration of agro-industrial wastewaters and isolation of organic
      compounds with high added values.
AB  - The aim of the current study was the exploitation of agro-industrial wastes or by
      products such as olive mill wastewater (OMW) and defective wines. A cost
      effective system for their maximum exploitation is suggested, using a combined
      process of membrane filtration and other physicochemical processes. Wastewaters
      are first treated in a membrane system (prefiltration, ultrafiltration,
      nanofiltration, and reverse osmosis) where pure water and other organic fractions
      (by-products) are obtained. Organic fractions, called hereafter byproducts and
      not wastes, are further treated for the separation of organic compounds and
      isolation of high added value products. Experiments were performed with OMW and
      defective wines as characteristic agro-industrial wastewaters. Profit from the
      exploitation of agro-industrial wastewaters can readily help the depreciation of
      the indeed high cost process of membrane filtration. The simple phenolic fraction
      of the OMW was successfully isolated from the rest of the waste, and problems
      occurring during winemaking, such as high volatile acidity and odours, were
      tackled. 

PMID- 24434989
TI  - Modelling ammonium-oxidizing population shifts in a biofilm reactor.
AB  - The dynamic reactor behaviour of a nitrifying inverse turbulent bed reactor,
      operated at varying loading rate, was described with a one-dimensional two-step
      nitrification biofilm model. In contrast with conventional biofilm models, this
      model includes the competition between two genetically different populations of
      ammonia-oxidizing bacteria (AOB), besides nitrite-oxidizing bacteria (NOB).
      Previously gathered experimental evidence showed that different loading rates in
      the reactor resulted in a change in the composition of the AOB community, besides
      a different nitrifying performance. The dissolved oxygen concentration in the
      bulk liquid was put forward as the key variable governing the experimentally
      observed shift from Nitrosomonas europaea (AOB1) to Nitrosomonas sp. (AOB2),
      which was confirmed by the developed one-dimensional biofilm model. Both steady
      state and dynamic analysis showed that the influence of microbial growth and
      endogenous respiration parameters as well as external mass transfer limitation
      have a clear effect on the competition dynamics. Overall, it was shown that the
      biomass distribution profiles of the coexisting AOB reflected the ecological
      niches created by substrate gradients. 

PMID- 24434990
TI  - Simultaneous carbon and nitrogen removal from municipal wastewater in full-scale
      unaerated/aerated submerged filters.
AB  - Characterization and evaluation of a biological submerged filter was carried out
      on a full-scale pilot plant performing removal of biochemical oxygen demand (BOD)
      and total nitrogen (TN) from pre-treated urban wastewater. The average influent
      values of BOD5, chemical oxygen demand (COD) and TN were 370, 1,015 and 60 mg/L,
      respectively. The pilot plant produced good discharge quality during steady-state
      operation. Average effluent BOD5, COD and TN values were 11, 58 and 15 mg/L,
      respectively. The reactor had been operating beyond its organic design capacity
      (200 population equivalent (PE)). At 480 PE the removal achieved for BOD, COD and
      TN were 98, 97 and 78%, respectively. This technology can absorb pollutant
      overloads while maintaining stable performance. Denitrification was performed by
      using sewage itself as carbon source. It was used as an intermittent aeration
      cycle in the unaerated cell to improve the denitrification process. The
      predenitrification with submerged unaerated filter has proved to be an efficient
      process for advanced removal of TN. 

PMID- 24434991
TI  - Of mice, men, and HTLV-1.
AB  - In this issue of Blood, Tezuka et al report the establishment of humanized mice
      infected by human T-cell leukemia virus type 1 (HTLV-1) that recapitulate adult T
      cell leukemia (ATL)-like leukemic symptoms and display HTLV-1-specific adaptive
      immune responses.

PMID- 24434992
TI  - A longer acting rFVIII, safe and effective.
AB  - In this issue of Blood, Mahlangu et al describe a well-designed and executed
      phase 3 multicenter study of a recombinant factor VIII (rFVIII) product fused
      with the Fc fragment of immunoglobulin G1 (IgG1) in 165 patients with severe
      hemophilia A.

PMID- 24434993
TI  - Determining the significance of MGUS.
AB  - In this issue of Blood, Turesson et al study the risk of progression of
      monoclonal gammopathy of undetermined significance (MGUS) to lymphoplasmacellular
      and myeloid malignancies in a large population, validating current risk factors
      and adding immunoparesis as a predictor of progression.

PMID- 24434994
TI  - Neutrophil survival in the death zone.
AB  - In this issue of Blood, Thompson et al reveal a key role for hypoxia-inducible
      factor (HIF)-2a in the adaptation of neutrophils to hypoxia. Tissue hypoxia is a
      common feature of trauma and inflammation. Infiltrating neutrophils must adapt to
      this low-oxygen environment to satisfy the metabolic and functional demands of an
      immune response.

PMID- 24434995
TI  - Preventing pregnancy loss.
AB  - In this issue of Blood, 2 articles by The Nimes Obstetricians and Hematologists
      Antiphospholipid Syndrome (NOH-APS) Study Group give us new information about the
      effects of low-molecular-weight heparin (LMWH) on pregnancy complications in
      women with prior pregnancy loss and either purely obstetric antiphospholipid
      syndrome (APS) or inherited thrombophilia. The results better define women at
      risk, suggest a role for LMWH, and confirm the need for further investigation.

PMID- 24434996
TI  - New molecule for mobilizing marrow stem cells.
AB  - In this issue of Blood, Zhang et al describe an exciting new small-molecule
      antagonist of CXCL12-CXCR4 binding with a potent ability to mobilize
      hematopoietic stem cells (HSCs). Further clinical development of this new
      drug,Me6TREN, may have broad applications in stem-cell mobilization for cancer
      and in regenerative medicine.

PMID- 24434997
TI  - Secreting von Willebrand factor in a Galpha-SNAP.
AB  - In this issue of Blood, Rusu et al use a state-of-the-art combination of
      pharmacological, genetic, and molecular techniques to dissect a mechanism for von
      Willebrand factor (vWF) secretion from endothelial cells mediated via Gaq/11 and
      Ga12 that can be triggered in basal or stimulated conditions. Indeed, although
      the storage of vWF in Weibel-Palade bodies (WPBs) of endothelial cells has been
      known for decades, the molecular mechanisms governing WPB docking with plasma
      membrane and vWF secretion remains undefined. One of the reasons this is still a
      very active area of investigation is that understanding the mechanism behind WPB
      docking is crucial for understanding potential pharmacological targets for
      pathological conditions associated with platelet aggregation/thrombi (e.g.,
      stroke), where vWF levels directly correlate with severity of disease progress.
      The work by Rusu et al opens up a new area of investigation into G-protein
      coupled receptors as triggers for WPB fusion at the plasma membrane and for vWF
      secretion.

PMID- 24434998
TI  - Patient-reported outcomes for the myelodysplastic syndromes: a new MDS-specific
      measure of quality of life.

PMID- 24434999
TI  - A highly specific blood test for vCJD.

PMID- 24435000
TI  - Application of CIBMTR risk score to NIH chronic GVHD at individual centers.

PMID- 24435002
TI  - Generalized law of friction between elastomers and differently shaped rough
      bodies.
AB  - In this paper, we study theoretically and experimentally the friction between a
      rough parabolic or conical profile and a flat elastomer beyond the validity
      region of Amontons' law. The roughness is assumed to be randomly self-affine with
      a Hurst exponent H in the range from 0 to 1. We first consider a simple Kelvin
      body and then generalize the results to media with arbitrary linear rheology. The
      resulting frictional force as a function of velocity shows the same qualitative
      behavior as in the case of planar surfaces: it increases monotonically before
      reaching a plateau. However, the dependencies on normal force, sliding velocity,
      shear modulus, viscosity, rms roughness, rms surface gradient and the Hurst
      exponent are different for different macroscopic shapes. We suggest analytical
      relations describing the coefficient of friction in a wide range of loading
      conditions and suggest a master curve procedure for the dependence on the normal
      force. Experimental investigation of friction between a steel ball and a
      polyurethane rubber for different velocities and normal forces confirms the
      proposed master curve procedure. 

PMID- 24435003
TI  - Relevance of the novel IASLC/ATS/ERS classification of lung adenocarcinoma in
      advanced disease.
AB  - Since the International Association for the Study of Lung Cancer (IASLC),
      American Thoracic Society (ATS) and European Respiratory Society (ERS) reported a
      new lung adenocarcinoma (ADC) classification, several groups have validated its
      association with prognosis in early stage disease. To our knowledge, there are no
      studies in advanced disease. We reviewed 313 patients with invasive lung ADC who
      were re-classified using the new IASLC/ATS/ERS criteria. Patients received
      platinum-based chemotherapy. Clinical characteristics, EGFR mutations, response
      and progression-free survival (PFS) after chemotherapy and overall survival were
      analysed. ADCs were classified as lepidic 7.4%, acinar 44.7%, papillary 10.1%,
      micropapillary 3.5% and solid 34.2%. When patterns were lumped into groups,
      response rates and PFS to platinum-based chemotherapy were better in high-grade
      ADC (micropapillary, papillary and solid-predominant) versus intermediate-grade
      ADC (lepidic and acinar-predominant) (36.9% versus 25.4% p=0.034 and 6.4 versus
      5.5 months p=0.009, respectively). Overall survival was better in high-grade ADC
      (25 versus 16.8; p=0.023). Factors associated with better overall survival were
      Eastern Cooperative Oncology Group (0-1), EGFR mutations and high-grade ADC.
      Prognostic differences found with the new classification in early disease may not
      apply to patients with advanced disease. Unlike in early stages, patients with
      high-grade ADC have longer overall survival compared with intermediate-grade ADC,
      probably due to a better response to chemotherapy. 

PMID- 24435004
TI  - Assessment of ventriculo-arterial interaction in pulmonary arterial hypertension
      using wave intensity analysis.

PMID- 24435006
TI  - IgG4-related disease in pulmonary arterial hypertension on long-term epoprostenol
      treatment.

PMID- 24435007
TI  - Pulmonary arterial compliance and exercise capacity after pulmonary
      endarterectomy.
AB  - Patients with chronic thromboembolic pulmonary hypertension (CTEPH), despite
      successful pulmonary endarterectomy (PEA), can continue to suffer from a
      limitation in exercise capacity. The objective of this study was to assess
      whether pulmonary arterial compliance is a predictor of exercise capacity after
      PEA. Right heart haemodynamics, treadmill incremental exercise test, spirometry,
      carbon monoxide transfer factor, arterial blood gas and echocardiographic
      examinations were retrospectively analysed in a population of CTEPH patients who
      underwent PEA at a single centre. Baseline and 3-month haemodynamic data were
      available in 296 patients; 5-year follow-up data were available in 68 patients.
      In a multivariable model the following parameters were found to be independent
      predictors of exercise capacity after surgery: age, sex, pulmonary arterial
      compliance, tricuspid annular plane excursion, arterial oxygen tension and carbon
      monoxide transfer factor (p<0.0001); the model showed good discrimination
      (Harrell's c=0.84) and calibration (shrinkage coefficient=0.91). Poor exercise
      capacity at 3 months was loosely associated with higher death rate during
      subsequent survival (Harrell's c=0.61). In conclusion, after successful PEA,
      reduced pulmonary arterial compliance is an important determinant of exercise
      capacity in association with the age and sex of the patients, and the extent of
      recovery of both cardiac and respiratory function. However, exercise capacity
      does not explain a large proportion of the effect of surgery on subsequent
      survival. 

PMID- 24435005
TI  - Targeting EGFR signalling in chronic lung disease: therapeutic challenges and
      opportunities.
AB  - Chronic respiratory diseases, including pulmonary fibrosis, chronic obstructive
      pulmonary disease (COPD) and lung cancer, are the second leading cause of death
      among Europeans. Despite this, there have been only a few therapeutic advances in
      these conditions over the past 20 years. In this review we provide evidence that
      targeting the epidermal growth factor receptor (EGFR) signalling pathway may
      represent a novel therapeutic panacea for treating chronic lung disease. Using
      evidence from human patient samples, transgenic animal models, and cell and
      molecular biology studies we highlight the roles of this signalling pathway in
      lung development, homeostasis, repair, and disease ontogeny. We identify
      mechanisms underlying lung EGFR pathway regulation and suggest how targeting
      these mechanisms using new and existing therapies has the potential to improve
      future lung cancer, COPD and pulmonary fibrosis patient outcomes. 

PMID- 24435008
TI  - Point-of-care urine test for assessing adherence to isoniazid treatment for
      tuberculosis.

PMID- 24435009
TI  - COPD and microalbuminuria: a 12-year follow-up study.
AB  - Chronic obstructive pulmonary disease (COPD), low lung function independent of
      diagnosis and markers of inflammation are all associated with increased morbidity
      and mortality. Microalbuminuria, reflecting endothelial dysfunction, could be a
      relevant inflammatory marker of potential systemic effects of COPD. We
      hypothesised that there was a positive association between microalbuminuria and
      mortality in individuals with COPD. We conducted a 12-year follow-up study of
      3129 participants in the second survey of the Nord-Trondelag Health Study (HUNT),
      Norway. At baseline, albuminuria was analysed in three urine samples and
      spirometry was performed. Among the participants, 136 had COPD and
      microalbuminuria, defined as a urinary albumin/creatinine ratio between 2.5 and
      30.0 mg.mmol(-1). The main outcome measures were hazard ratio of all-cause
      mortality according to microalbuminuria. Compared to those with COPD without
      microalbuminuria, the adjusted hazard ratio for all-cause mortality in those with
      COPD and microalbuminuria was 1.54, 95% CI 1.16-2.04. This result was similar
      after excluding cardiovascular disease at baseline. Classifying COPD severity by
      Global Initiative for Chronic Obstructive Lung Disease, there was a positive
      association trend with increasing severity stages. Microalbuminuria is associated
      with all-cause mortality in individuals with COPD and could be a relevant tool in
      identification of patients with poor prognosis.

PMID- 24435010
TI  - Localized surface plasmon resonance sensors based on wavelength-tunable spectral
      dips.
AB  - Localized surface plasmon resonance (LSPR) sensors serve as sensitive analytical
      tools based on refractive index changes, which can be applied to affinity-based
      chemical sensing and biosensing. However, to select the monitoring wavelength,
      monodisperse Au or Ag nanoparticles must be synthesized. Here we developed LSPR
      sensors that operate at arbitrary wavelengths after preirradiation at the
      corresponding wavelength. Polydisperse plasmonic Ag nanospheroids or nanorods are
      photocatalytically deposited on TiO2. The nanoparticle ensemble shows a broad
      absorption band over the visible and near infrared regions, and absorption dips
      can be formed at desired wavelengths simply by photoexciting the ensemble at the
      wavelengths, on the basis of plasmon-induced charge separation. The dips redshift
      linearly in response to a positive change of refractive index, and the refractive
      index sensitivity linearly increases with increasing dip wavelength (e.g., 356 nm
      RIU(-1) at 1832 nm). The dip-based sensor is applied to monitoring of selective
      binding between biotin and streptavidin. The present system would allow
      development of miniaturized and cost-effective sensors that operate at the
      optimum wavelength at which the sensitivity is highest within the optical window
      of the sample. 

PMID- 24435011
TI  - Being good enough to prevent the worst.

PMID- 24435012
TI  - The relationship between local public health agency administrative variables and
      county health status rankings in Kentucky.
AB  - OBJECTIVES: The purpose of this research study was to determine whether specific
      local public health agency (LPHA) characteristics were associated with favorable
      county health status. Specifically, financial and administrative comparisons were
      made to determine whether variables such as budget size or number of employees,
      among others, were associated with community health status among the 120 counties
      in Kentucky. Other financial and administrative variables collected from LPHA
      data were also investigated in this study. METHODS: Administrative and financial
      data were collected for each local public health agency in Kentucky. This was
      matched with data on the health status of Kentucky counties from the 2010
      University of Wisconsin MATCH (Mobilizing Action Towards Community Health
      Assessment) counties in select measures of health. MATCH data used included
      measures of health outcomes, specifically socioeconomic status (SES), mortality,
      and morbidity. Logistic regressions were used to determine the relationship, if
      any, between variations in the health agency data variables, SES, and health
      status. RESULTS: Analysis suggests that SES is the strongest link to county
      health status. Several other variables that appear to have statistically
      significant association with health status include the education level of the
      director, whether the LPHA employees received a raise, whether the LPHA had an
      associated Home Health agency, and the amount of money used from their reserve
      account to balance the LPHA budget. CONCLUSIONS: For many years, public health in
      Kentucky has measured the number of clinical visits and other LPHA services but
      failed to determine specific characteristics and variables that influence
      community health status. This study suggests that LPHAs in Kentucky can advance
      public health practice by having well-educated directors, giving annual
      incremental raises, and utilizing the agency reserve funds to meet budget
      shortfalls in the short run. Furthermore, LPHAs with an associated home health
      agency may need to reassess their impact and need in their community, considering
      the negative effect it may have on county health status.

PMID- 24435013
TI  - Putting diabetes on the map: what does population health really look like at the
      local level?
AB  - Population health data are used to profile local conditions, call attention to
      areas of need, and evaluate health-related programs. Demand for data to inform
      health care decision making has spurred development of data sources and online
      systems, but these are often poorly integrated or limited in scope. Our objective
      was to identify existing data about diabetes mellitus-related conditions in
      Minnesota, build an online data resource, and identify what data are currently
      missing that, if available, would better inform assessment of health conditions
      in the state. A Web site was developed and populated with existing data and data
      not available elsewhere. It features functionality identified as most important
      by users, such as maps and county profiles. The site could serve as a flexible
      tool for stakeholder engagement, but issues were identified during development,
      including concerns about interpreting map data and open questions about
      sustainability, that need to be addressed.

PMID- 24435014
TI  - The effects of the April 2011 tornado outbreak on personal preparedness in
      Jefferson County, Alabama.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of a tornado
      disaster on the personal preparedness of local residents to determine (1) to what
      extent the tornado outbreak experience had altered preparedness awareness,
      willingness to act, and levels of personal preparedness of residents as measured
      by possession of a preparedness kit; and (2) what effect this experience had on
      the variables associated with having a complete disaster preparedness kit.
      DESIGN: Two random digit-dialed surveys were completed following the Behavioral
      Risk Factor Surveillance System protocols. The pre-tornado survey was conducted
      between October and December 2010 and the post-tornado survey was conducted
      between January and March 2012. RESULTS: After the April 2011 tornado outbreak,
      86.08% of the respondents (n = 1364) reported that they had thought more about
      personal or family preparedness and 59.65% (n = 907) reported that they had taken
      actions to increase their level of preparedness. Overall, general awareness of
      preparedness media campaigns increased significantly (almost 24%; P < .0001), as
      did the percentage of those having a complete disaster preparedness kit (a 66%
      increase, not quite doubled from 2010 to 2012; P < .0001). CONCLUSIONS: Findings
      of the study indicate that the disaster had a significant impact on the local
      residents' (1) awareness of preparedness campaigns, (2) awareness of the need to
      be prepared, (3) willingness to become better prepared, and (4) possession of a
      disaster and emergency preparedness kit and its associated items.

PMID- 24435015
TI  - Use of syndromic surveillance at local health departments: movement toward more
      effective systems.
AB  - CONTEXT: Syndromic surveillance systems enhance public health practice in both
      large and small population settings. However, data from these systems are
      typically monitored by state and federal agencies and less frequently used by
      small public health agencies, such as local health departments (LHDs). Syndromic
      surveillance system modifications may facilitate use by LHDs. OBJECTIVE: To
      describe syndromic surveillance system modifications and survey LHD staff to
      assess subsequent changes in system use. DESIGN: Pre- and postintervention cross
      sectional analysis. SETTING: North Carolina (NC) LHDs, 2009 and 2012.
      PARTICIPANTS: LHD nursing and preparedness staff. MAIN OUTCOME MEASURES: Use of
      syndromic surveillance data by LHDs for outbreak response, seasonal event
      response, program management, and stakeholder reports. RESULTS: In NC, syndromic
      surveillance system modifications made between 2009 and 2012 included
      implementation of LHD-specific data "dashboards" and increased distribution of
      LHD-specific surveillance information by the state public health agency. Users of
      LHD syndromic surveillance system increased from 99 in 2009 to 175 in 2012.
      Twenty-seven of 28 (96%) and 62 of 72 (86%) respondents completed the 2009 and
      2012 surveys, respectively. Among respondents, 23% used syndromic surveillance
      data for outbreak response in 2009, compared with 25% in 2012. In 2009, 46% of
      respondents used these data for seasonal event response, compared with 57% in
      2012. Syndromic surveillance data were used for program management by 25% of
      respondents in 2009 (compared with 30% in 2012) and for stakeholder reports by
      23% of respondents in 2009 (compared with 33% in 2012). CONCLUSIONS: Syndromic
      surveillance system changes supported modest increases in LHD use of syndromic
      surveillance information. Because use of syndromic surveillance information at
      smaller LHD is rare, these modest increases indicate effective modification of
      the NC syndromic surveillance system.

PMID- 24435016
TI  - On the coupling of solvent characteristics to the electronic structure of solute
      molecules.
AB  - We present the results of a theoretical investigation focusing on the solvent
      structure surrounding the -1, 0 and +1 charged species of F, Cl, Br and I halogen
      atoms and F2, Cl2, Br2 and I2 di-halogen molecules in a methanol solvent and its
      influence on the electronic structure of the solute molecules. Our results show a
      large stabilizing effect arising from the solute-solvent interactions. Well
      formed first solvation shells are observed for all species, the structure of
      which is strongly influenced by the charge of the solute species. Detailed
      analysis reveals that coordination number, CN, solvent orientation, theta, and
      solute-solvent distance, d, are important structural characteristics which are
      coupled to changes in the electronic structure of the solute. We propose that the
      fundamental chemistry of any solute species is generally regulated by these
      solvent degrees of freedom. 

PMID- 24435017
TI  - How dolphins see the world: a comparison with chimpanzees and humans.
AB  - Bottlenose dolphins use auditory (or echoic) information to recognise their
      environments, and many studies have described their echolocation perception
      abilities. However, relatively few systematic studies have examined their visual
      perception. We tested dolphins on a visual-matching task using two-dimensional
      geometric forms including various features. Based on error patterns, we used
      multidimensional scaling to analyse perceptual similarities among stimuli. In
      addition to dolphins, we conducted comparable tests with terrestrial species:
      chimpanzees were tested on a computer-controlled matching task and humans were
      tested on a rating task. The overall perceptual similarities among stimuli in
      dolphins were similar to those in the two species of primates. These results
      clearly indicate that the visual world is perceived similarly by the three
      species of mammals, even though each has adapted to a different environment and
      has differing degrees of dependence on vision. 

PMID- 24435018
TI  - Longitudinal polysomnographic assessment from acute to subacute phase in
      infratentorial versus supratentorial stroke.
AB  - BACKGROUND: Regulation of sleep and sleep-related breathing resides in different
      brain structures. Vascular lesions can be expected to differ in their
      consequences on sleep depending on stroke topography. However, studies addressing
      the differences in sleep and sleep-related breathing depending on stroke
      topography are scarce. The aim of the present investigation was to compare the
      sleep and sleep-related breathing of patients with supratentorial versus
      infratentorial stroke. METHODS: This study was part of the prospective
      multicenter study SAS-CARE-1 (Sleep-Disordered Breathing in Transient Ischemic
      Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP)
      Treatment Efficacy (SAS-CARE); NCT01097967). We prospectively included 14
      patients (13 male, age 66 +/- 6 years) with infratentorial lesions and 14
      patients (14 male, age 64 +/- 7 years) with supratentorial lesions, matched for
      age and stroke severity. Polysomnography was recorded in all during the acute
      phase within 9 days after stroke onset and 3 months later. RESULTS: During the
      acute phase after stroke, patients with infratentorial lesions had significantly
      more sleep-related breathing disorders than patients with supratentorial lesions
      with an apnea-hypopnea index >20 observed in 8 (57%) patients with infratentorial
      stroke and in only 2 (14%) patients with supratentorial stroke. Sleep-related
      breathing improved from the acute to the subacute phase (3 months), albeit
      remaining elevated in a significant proportion of subjects. Sleep parameters did
      not differ between the two patient groups but there was a general improvement of
      sleep from the acute to the subacute phase which was comparable for both patient
      groups. Although stroke severity was mild, recovery after 3 months was worse in
      patients with infratentorial stroke with 12 of 14 patients with supratentorial
      stroke being symptom free (NIHSS = 0), while this was the case for only 6 of 14
      patients with infratentorial stroke. CONCLUSIONS: Patients with infratentorial
      lesions are at an increased risk for sleep-related breathing disorders, which are
      frequent in this group. Monitoring of sleep-related breathing is therefore
      especially recommended in patients with infratentorial stroke. Because of the
      absence of reliable differences in sleep parameters between the two patient
      groups, polygraphy, with reduced diagnostic costs, rather than polysomnography
      could be considered. The higher prevalence of sleep-related breathing disorders
      and the poorer recovery of patients with infratentorial lesions suggest that
      early treatment interventions should be considered.

PMID- 24435019
TI  - Chemoradiation therapy versus chemotherapy alone for gastric cancer after R0
      surgical resection: a meta-analysis of randomized trials.
AB  - OBJECTIVE: Current national guidelines include category 1 recommendations for
      perioperative chemotherapy or adjuvant chemoradiation with surgical resection for
      patients with stage IB-IIIB gastric cancer. We conducted a meta-analysis of
      randomized trials in which chemotherapy was prospectively tested against
      chemoradiation with surgical resection. METHODS: We electronically searched
      PubMed and EMBASE for randomized, controlled clinical trials involving patients
      with gastric adenocarcinoma, status post-R0 resection. The interventions compared
      were adjuvant chemotherapy versus chemoradiation, with any chemotherapy regimen.
      The primary outcomes of interest were disease-free survival and overall survival.
      The Mantel-Haenszel random-effects model was used to calculate effect sizes.
      RESULTS: Six trials that included 1,171 patients were evaluated; 599 were
      randomized to adjuvant chemoradiation and 572 to chemotherapy alone.
      Chemoradiation was associated with a significant increase in disease-free
      survival (odds ratio 1.48, 95% confidence interval 1.08-2.03) when compared to
      chemotherapy alone. However, there was no significant difference in overall
      survival (odds ratio 1.27, 95% confidence interval 0.95-1.71). Five trials found
      no statistically significant differences in toxicities between the two groups.
      CONCLUSION: In patients with gastric cancer status post-R0 resection, adjuvant
      chemoradiation was associated with higher disease-free survival when compared to
      chemotherapy alone. It remains appropriate to design trials testing new systemic
      agents with radiotherapy.

PMID- 24435021
TI  - Cardiorespiratory impact of transesophageal endoscopic mediastinoscopy compared
      with cervical mediastinoscopy: a randomized experimental study.
AB  - BACKGROUND: Transesophageal natural-orifice transluminal endoscopic surgery
      (NOTES) mediastinoscopy has been described as a feasible, less-invasive
      alternative to video-assisted mediastinoscopy (VAM). We aimed to investigate
      hemodynamic and respiratory effects during transesophageal NOTES mediastinoscopy
      compared with VAM. PATIENTS AND METHODS: This was a short-survival experiment in
      20 female pigs randomized to NOTES (n = 10) or VAM (n = 10) mediastinoscopy. In
      the NOTES group, an endoscopist accessed the mediastinum through a 5-cm
      submucosal tunnel in the esophageal wall, and CO2 was used to create the
      pneumomediastinum. Conventional VAM was carried out by thoracic surgeons. A 30
      minute systematic exploration of the mediastinum was then performed, including
      invasive monitoring for hemodynamic and respiratory data. Blood samples were
      drawn for gas analyses. RESULTS: All experiments except 2 in the NOTES group (one
      because of technical difficulties, the other because of thoracic lymphatic duct
      lesion) were completed as planned, and animals survived 24 hours. Also, 3 animals
      in the NOTES group presented a tension pneumothorax that was immediately
      recognized and percutaneously drained. VAM and NOTES animals showed similar
      pulmonary and systemic hemodynamic behavior during mediastinoscopy. Pulmonary gas
      exchange pattern was mildly impaired during the NOTES procedure, showing lower
      partial arterial oxygen pressure associated with higher airway pressures (more
      important in animals that presented with pneumothorax). CONCLUSIONS: NOTES
      mediastinoscopy induces minimal deleterious respiratory effects and hemodynamic
      changes similar to conventional cervical VAM and could be feasible when performed
      under strict hemodynamic and respiratory surveillance. Notably, serious
      complications caused by the injury of pleura are more frequent in NOTES, which
      mandates an improvement in technique and suitable equipment.

PMID- 24435020
TI  - Drawing a high-resolution functional map of adeno-associated virus capsid by
      massively parallel sequencing.
AB  - Adeno-associated virus (AAV) capsid engineering is an emerging approach to
      advance gene therapy. However, a systematic analysis on how each capsid amino
      acid contributes to multiple functions remains challenging. Here we show proof-of
      principle and successful application of a novel approach, termed AAV Barcode-Seq,
      that allows us to characterize phenotypes of hundreds of different AAV strains in
      a high-throughput manner and therefore overcomes technical difficulties in the
      systematic analysis. In this approach, we generate DNA barcode-tagged AAV
      libraries and determine a spectrum of phenotypes of each AAV strain by Illumina
      barcode sequencing. By applying this method to AAV capsid mutant libraries tagged
      with DNA barcodes, we can draw a high-resolution map of AAV capsid amino acids
      important for the structural integrity and functions including receptor binding,
      tropism, neutralization and blood clearance. Thus, Barcode-Seq provides a new
      tool to generate a valuable resource for virus and gene therapy research. 

PMID- 24435022
TI  - Insufficient coping behavior under chronic stress and vulnerability to
      psychiatric disorders.
AB  - BACKGROUND: Epidemiological data indicate that 75% of subjects with major
      psychiatric disorders have their onset of illness in the age range of 17-24
      years. An estimated 35-50% of college and university students drop out
      prematurely due to insufficient coping skills under chronic stress, while 85% of
      students receiving a psychiatric diagnosis withdraw from college/university prior
      to the completion of their education. In this study, we aimed at developing
      standardized means of identifying students with insufficient coping skills under
      chronic stress and at risk for mental health problems. SAMPLING AND METHODS: A
      sample of 1,217 college students from 3 different sites in the USA and
      Switzerland completed 2 self-report questionnaires: the Coping Strategies
      Inventory (COPE) and the Zurich Health Questionnaire (ZHQ), which assesses
      'regular exercises', 'consumption behavior', 'impaired physical health',
      'psychosomatic disturbances' and 'impaired mental health'. The data were
      subjected to structure analyses by means of a neural network approach. We found 2
      highly stable and reproducible COPE scales that explained the observed
      interindividual variation in coping behavior sufficiently well and in a
      socioculturally independent way. The scales reflected basic coping behavior in
      terms of 'activity-passivity' and 'defeatism-resilience', and in the sense of
      stable, socioculturally independent personality traits. RESULTS: Correlation
      analyses carried out for external validation revealed a close relationship
      between high scores on the defeatism scale and impaired physical and mental
      health. This underlined the role of insufficient coping behavior as a risk factor
      for physical and mental health problems. CONCLUSION: The combined COPE and ZHQ
      instruments appear to constitute powerful screening tools for insufficient coping
      skills under chronic stress and for risks of mental health problems.

PMID- 24435023
TI  - Inguinal lymph nodes: size, number, and other characteristics in asymptomatic
      patients by CT.
AB  - PURPOSE: The purpose of this study was to establish normative data for the CT
      appearance of inguinal lymph nodes. MATERIALS AND METHODS: After Institutional
      Review Board approval, search of the radiology information system identified 500
      consecutive CT examinations of the pelvis. Patients were included if no lower
      extremity or perineum pathology, or history of malignancy at the time of CT
      examination, and a clinical note documenting no tumor at least 2 years after the
      CT. The final study group was 77 patients. CT examinations were retrospectively
      reviewed and bilateral inguinal lymph nodes were characterized by size (short
      axis and largest size in general), number, and presence of fat attenuation.
      RESULTS: The mean short-axis inguinal lymph node size was 5.4 mm (range 2.1-13.6
      mm), measured at 8.8 mm two standard deviations above the mean. The mean number
      of superficial and deep inguinal lymph nodes was 10.7 (range 3-18) and 1.2 per
      patient (range 1-2), respectively. Superficial and deep inguinal nodes showed
      internal fat attenuation in 85 and 78% of nodes, and were oval in shape in 95 and
      78%, respectively. CONCLUSION: Inguinal lymph nodes in asymptomatic patients have
      a mean short axis of 5.4 mm, a short axis of 8.8 mm at two standard deviations
      above the mean, and are multiple and symmetric in size and number (4-20 per
      patient). Normal inguinal lymph nodes were commonly oval in shape and contained
      fat, although such findings may be absent in smaller lymph nodes.

PMID- 24435024
TI  - Complex split cord malformation type 1 with mulitiple lipomas involving the split
      cord.

PMID- 24435025
TI  - Randomized trial of an electronic personal health record for patients with
      serious mental illnesses.
AB  - OBJECTIVE: The authors evaluated the effect of an electronic personal health
      record on the quality of medical care in a community mental health setting.
      METHOD: A total of 170 individuals with a serious mental disorder and a comorbid
      medical condition treated in a community mental health center were randomly
      assigned to either a personal health record or usual care. One-year outcomes
      assessed quality of medical care, patient activation, service use, and health
      related quality of life. RESULTS: Patients used the personal health record a mean
      of 42.1 times during the 1-year intervention period. In the personal health
      record group, the total proportion of eligible preventive services received
      increased from 24% at baseline to 40% at the 12-month follow-up, whereas it
      declined in the usual care group, from 25% to 18%. In the subset of patients with
      one or more cardiometabolic conditions (N=118), the total proportion of eligible
      services received improved by 2 percentage points in the personal health record
      group and declined by 11 percentage points in the usual care group, resulting in
      a significant difference in change between the two groups. There was an increase
      in the number of outpatient medical visits, which appeared to explain many of the
      significant differences in the quality of medical care. CONCLUSIONS: Having a
      personal health record resulted in significantly improved quality of medical care
      and increased use of medical services among patients. Personal health records
      could provide a relatively low-cost scalable strategy for improving medical care
      for patients with comorbid medical and serious mental illnesses.

PMID- 24435026
TI  - Multifactorial, multi-systemic and potentially severe disease.

PMID- 24435027
TI  - New autoantibodies and their clinical associations in juvenile myositis - a
      systematic review.
AB  - BACKGROUND: Novel autoantibodies targeting intracellular proteins are recently
      detected in patients with idiopathic inflammatory myopathies (IIMs). OBJECTIVE:
      To evaluate the prevalence of these myositis-specific antibodies (MSAs) in
      juvenile IIMs (JIIMs) and their association with clinical characteristics and
      disease course. METHODS: A systematic literature search was carried out to
      identify all studies concerning these novel MSAs (p155/140, p140, CADM-140, SAE
      and 200/100) in patients with JIIMs. RESULTS: A total of 1003 references were
      identified, of which 118 were selected for detailed analysis and 13 included in
      the final review. CONCLUSIONS: The anti-p155/140, the anti-p140 and the anti-CADM
      140 seem to be useful markers for define distinct clinical subsets and for
      predicting prognosis of JIIMs. Further studies are needed to clarify the
      importance of anti 200/100 and anti-SAE in juvenile myositis.

PMID- 24435028
TI  - Systemic Lupus Erythematosus activity and serum bilirubins.
AB  - BACKGROUND: Serum bilirubins play an important role in controlling oxidative
      stress; there is increased oxidative stress during activity of rheumatic diseases
      such as systemic lupus erythematosus (SLE). OBJECTIVE: To study bilirubin levels
      in SLE (Systemic Lupus Erythematosus) patients and relate them to disease
      activity. METHODS: We analyzed levels of total bilirubins (TB), direct bilirubins
      (DB) and indirect bilirubins (IB), sedimentation rate (ESR) and C reactive
      protein (CRP) in 143 SLE patients. Data were collected on the clinical and
      autoantibody profiles and patients underwent measurement of SLEDAI and SLICC .
      RESULTS: Correlation of indirect bilirubin values with SLEDAI was negative
      (p=0.02; Spearman rho=-0.18). Comparing the levels of IB according to the
      clinical activity profile we observed associations with increase of anti DNA
      titer (p=0.027) and with decrease in complement levels (p=0.017). ESR correlated
      negatively with IB levels (p=0.01) but CRP did not (p=0.15). In a multiple linear
      regression analysis only the increase in ESR titer remained significant. SLICC
      values were not correlated with TB (p=0.30), DB (p=0.12) or IB (p=0.31).
      CONCLUSIONS: We conclude that IB levels in SLE correlate negatively with disease
      activity. IB levels are lower in patients with higher ESR.

PMID- 24435029
TI  - Clinical and vascular features of Takayasu arteritis at the time of ischemic
      stroke.
AB  - OBJECTIVES: Takayasus arteritis (TA) is a systemic vasculitis whose clinical
      presentation varies from asymptomatic to serious neurovascular events, including
      stroke. However, few studies are currently available assessing stroke in TA.
      Thus, we described the clinical and laboratory characteristics and vascular
      imaging features in patients with TA at the time of stroke. MATERIALS AND
      METHODS: This is a single center retrospective cohort study investigating the
      clinical and demographic data of 18 (15.0%) patients with a history of stroke
      confirmed by imaging methods, among 120 patients with TA, assessed in the 1985
      2012 period. RESULTS: The mean age of the 18 patients at the time of stroke was
      29.4+/-10.9 years, with 94.4% female and 88.9% Caucasian. Of these patients, 14
      (77.8%) had previous stroke at diagnosis of TA, while in four cases the stroke
      occurred after confirmed TA diagnosis. Regarding the clinical course, 12 (66.7%)
      had peripheral neurological sequelae and one patient died as a result of cerebral
      hyperperfusion syndrome after carotid revascularization. CONCLUSIONS: Our results
      showed a high prevalence of stroke in TA and revealed most of these events
      occurred concomitantly with diagnosed TA. Moreover, although four patients had
      strokes after diagnosis of TA, these occurred at a young age, demonstrating they
      were most likely the result of vascular changes secondary to TA.

PMID- 24435030
TI  - Psychiatric disorders and MRI brain findings in patients with systemic lupus
      erythematosus and Behcet's disease: a cross sectional study.
AB  - INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE) shows some
      similarities to neuroBehcet?'s disease (NBD). AIM OF THE WORK: to investigate and
      compare the psychiatric manifestations in a cohort of patients of systemic lupus
      erythematosus (SLE ) versus Behcet's Disease (BD). Also, a comparison of MRI
      brain findings in SLE patients and BD patients presented with psychiatric
      disorders was done. Finally, we correlate these manifestations with disease
      activity indices of the patients. PATIENT AND METHOD: The study included 50
      patients of SLE, 34 patients of Behcet's disease (BD) and 44 healthy volunteers
      as a control group. All patients were subjected to psychiatric interview to
      diagnose any psychiatric disorders clinically. MRI brain was done for SLE
      patients and BD patients presented with psychiatric disorders. Overall clinical
      assessment and disease activity of SLE and BD were evaluated. RESULTS:
      Psychiatric disorders were detected in 28 (56%) of SLE patients which were
      significantly more prevalent than psychiatric disorders that were detected in 9
      (26.47%) of BD patients. Psychiatric disorders in healthy volunteers were
      significantly less prevalent than either SLE patients or BD patients. MRI brain
      of SLE patients presented with psychiatric disorders commonly showed cerebral
      white matter abnormalities while in BD patients presented with psychiatric
      disorders commonly showed brain stem lesions. CONCLUSION: (1) High prevalence of
      psychiatric disorders in SLE and BD with a higher significant prevalence in SLE.
      (2) Evident MRI brain findings in SLE and BD patients presented with psychiatric
      disorders.

PMID- 24435031
TI  - Using a multifactorial approach to determine fall risk profiles in portuguese
      older adults.
AB  - AIM: The aim of this study was to use a multifactorial approach to characterize
      episodic and recurrent fallers risk profiles in Portuguese older adults.
      MATERIALS AND METHODS: To accomplish the mentioned purpose, 1416 Portuguese older
      adults above 65 years were tested with three different field measurements: 1)
      health and falls questionnaire; 2) Physical Activity questionnaire and 3) a set
      of functional fitness tests. The subjects were divided in three different groups
      according to fall prevalence: non-fallers, subjects who did not report any falls
      during the previous year, episodic fallers, those who reported to have fallen
      only once during the previous year, and recurrent fallers, the ones that fell
      twice or more times during the previous year. Episodic and Recurrent fallers risk
      profiles were established using multifactorial logistic regression models in
      order to avoid confounding effects between the variables. RESULTS: The results
      showed that age was not a risk factor for either episodic or recurrent falling.
      In addition, health parameters were shown to be the factors distinguishing
      recurrent from episodic fallers. This may imply that, comparing with episodic
      falls, recurrent falls are more associated with higher presence of chronic
      conditions and are less likely to occur due to external factors. Furthermore,
      being a woman, having fear of falling and lower functional fitness levels were
      determinant factors for both episodic and recurrent falls. It is also important
      to note that, although total physical activity was only related with episodic
      falling, promoting physical activity and exercise may be the easiest and cheapest
      way to improve functional fitness and health levels and therefore, its role in
      fall prevention should not be underestimated. CONCLUSIONS: The results of this
      study reinforce the importance of using a multifactorial approach, not only
      focusing on cognitive-behavioral factors, but also on promoting physical activity
      and healthy lifestyles, when assessing fall risk or planning an intervention
      aiming at fall prevention within the older population.

PMID- 24435032
TI  - Juvenile systemic lupus erythematosus in Portugal: clinical and immunological
      patterns of disease expression in a cohort of 56 patients.
AB  - OBJECTIVE: To define the pattern of disease expression and to gain better
      understanding in patients with juvenile onset systemic lupus erythematosus (SLE)
      in Portugal. METHODS: The features of unselected patients with systemic lupus
      erythematosus who had disease onset before the age of 18 years were
      retrospectively analysed in three Portuguese centres with Pediatric Rheumatology
      Clinic over a 24-year period (1987-2011). Demographic, clinical and laboratory
      manifestations, therapy and outcome were assessed. RESULTS: A cohort of 56
      patients with a mean age at disease onset of 12.6 +/- 4.04 years (mean +/- 1SD)
      (range, 1.0-17.0 years) and a mean period of follow-up of 5.5 +/- 5.4 years.
      Forty six (82.1%) patients were female. The most common disease manifestations
      were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological
      abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and
      consisted of glomerular nephritis in all cases. Neuropsychiatric manifestations
      occurred in 21.4% but severe central nervous system complications were uncommon,
      as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear
      antibodies and anti-double stranded DNA were positive in most patients in (98.2%
      and 71.4% respectively), as well as low C3 and/or C4 were observed frequently
      (85.7%). Generally, most patients had a good response to therapy as demonstrated
      by a significant decreasing of SLEDAI score from disease presentation to the last
      evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of
      complications were significantly higher in patients with neurolupus and/or lupus
      nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%),
      azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six
      (10.7%) patients were treated with rituximab. Long-term remission was achieved in
      32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6%
      and complications/severe manifestations in 23.2%. Two patients died, being active
      disease and severe infection the causes of death. CONCLUSIONS: This study
      suggests that in our patients the clinical and laboratory features observed were
      similar to juvenile systemic lupus erythematosus patients from other series.
      Clinical outcome was favourable in the present study. Complications from therapy
      were frequent.

PMID- 24435033
TI  - Uncommon pathological findings in sural nerve biopsy from a patient with Churg
      Strauss related multiple mononeuropathy.
AB  - We describe a patient with severe multiple mononeuropathy associated with
      hypereosinophilia, asthma and pulmonary non cavitating micronodules. Sural nerve
      biopsy revealed marked perineural thickening and microfasciculation with
      inflammatory infiltrates in the perinerium and in the epinerium. The patient
      markedly improved with steroid therapy. Our final diagnosis was Churg-Strauss
      related multiple mononeuropathy. Thus, we report a case of Churg-Strauss related
      multiple mononeuropathy with uncommon pathological findings on sural nerve and we
      underline the importance of clinical evaluation for this diagnosis. 

PMID- 24435034
TI  - Off-label use of rituximab in systemic rheumatic diseases: case series and
      review.
AB  - B-cells play an important role not only in cellular but also in humoral immunity
      through differentiation into plasma cells and antibody production. B-cell
      depletion may, theoretically, change the course of systemic rheumatic diseases
      (SRD) in which self-reactive antibodies are part of the pathogenic pathway. In
      Rheumatology, anti-B-cell antibody Rituximab is currently licensed for the
      treatment of rheumatoid arthritis, however there is growing evidence of its
      potential use in other SRD. The authors present a case series of eight patients
      in which Rituximab was used off-label including overlap syndrome Rhupus, systemic
      lupus erythematosus and Wegener's granulomatosis. In the end, a brief literature
      review about this subject is performed. 

PMID- 24435035
TI  - Wegener's granulomatosis and alveolar hemorrhage - case report.
AB  - The authors present a clinical case of 55 years old female patient with limited
      form of Wegener's granulomatosis (WG), which first manifestation was non-erosive
      polyarthritis with rheumatoid factor positive that antedates one decade the
      pulmonary manifestations. She had acute episodes with purulent expectoration,
      fever and hemoptysis, with resolution in a week. The chest x-rays demonstrated
      migratory bilateral pulmonary infiltrates. Transthoracic lung biopsy was
      performed and revealed capilaritis and signs of old and recent hemorrhage. At
      that time, autoimmunity study was repeated and showed positive for rheumatoid
      factor, negative anti-cyclic citrullinated peptide antibodies (anti-CCP) and high
      sustained PR3 anti-neutrophil cytoplasmic antibodies. The diagnosis of WG was
      established and cyclophosphamide started. This patient had a less common
      presentation and a less common histological pattern compared to the typical
      necrotizing granulomatous inflammation. She was treated with immunosuppression
      therapy which could have contributed to a mild clinical expression and a lower
      diagnostic yield. In suspicious cases, repeat the autoimmunity study, when facing
      new findings, could confirm the correct diagnosis.

PMID- 24435036
TI  - The effect of etanercept on a case of amyloidosis secondary to ankylosing
      spondylitis: results of 2-year follow-up.
AB  - Secondary amyloidosis (type AA) is rarely encountered but can be a significant
      complication of ankylosing spondylitis (AS) and may lead to proteinuria and renal
      dysfunction. Anti-tumor necrosis factor-alpha (anti-TNFalpha) agents may be used
      to induce clinical remission by suppressing systemic inflammation in secondary
      amyloidosis. The patient described , with the diagnosis of AS, was diagnosed with
      secondary amyloidosis, despite treatment with disease modifying anti-rheumatic
      medication. He developed marked proteinuria, renal dysfunction and low levels of
      serum albumin. Diagnosis of amyloidosis was confirmed by renal biopsy. During a 2
      year treatment period with etanercept, an anti-TNFalpha agent, a definite
      improvement was determined in all parameters. This case illustrates that in the
      treatment of secondary amyloidosis related to AS, etanercept, an anti-TNF alpha
      agent, can be considered an effective therapeutic option. 

PMID- 24435037
TI  - Antineutrophil cytoplasmatic antibody positive systemic vasculitis in a patient
      treated with propylthiouracil.
AB  - The development of antineutrophil cytoplasmatic antibody (ANCA) during therapy
      with propylthiouracil (PTU) is not uncommon but occasionally has clinical
      significance. Risk factors associated with the development of ANCA associated
      systemic vasculitis when taking PTU have been described. We report and discuss a
      case with PTU-induced ANCA vasculitis with severe systemic manifestations. 

PMID- 24435038
TI  - Central nervous system vasculitis.

PMID- 24435039
TI  - An uncommon cause of sciatic nerve paralysis.

PMID- 24435040
TI  - Reversed halo sign in organizing pneumonia secondary to rheumatoid arthritis.

PMID- 24435041
TI  - IgA nephropathy in an ankylosing spondylitis patient during infliximab therapy:
      chicken, egg or mother and child reunion?

PMID- 24435042
TI  - Reactivity of gold nanoparticles towards N-heterocyclic carbenes.
AB  - The reaction of gold nanoparticles with benzimididazol-2-ylidene ligands leads to
      the formation of well-defined bis-carbene gold(i) complexes, as shown by
      characterization techniques such as powder XRD and solid state NMR. 

PMID- 24435043
TI  - An imaging-based platform for high-content, quantitative evaluation of
      therapeutic response in 3D tumour models.
AB  - While it is increasingly recognized that three-dimensional (3D) cell culture
      models recapitulate drug responses of human cancers with more fidelity than
      monolayer cultures, a lack of quantitative analysis methods limit their
      implementation for reliable and routine assessment of emerging therapies. Here,
      we introduce an approach based on computational analysis of fluorescence image
      data to provide high-content readouts of dose-dependent cytotoxicity, growth
      inhibition, treatment-induced architectural changes and size-dependent response
      in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and
      pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of
      clinically relevant cytotoxic modalities and appropriately designed controls for
      reliable quantification of fluorescence signal. This streamlined methodology
      reads out the high density of information embedded in 3D culture systems, while
      maintaining a level of speed and efficiency traditionally achieved with global
      colorimetric reporters in order to facilitate broader implementation of 3D tumour
      models in therapeutic screening. 

PMID- 24435045
TI  - Clinical course of asymptomatic adult moyamoya disease.
AB  - BACKGROUND: As regular medical check-ups are becoming more common, the prevalence
      of asymptomatic moyamoya disease (MMD) is increasing. However, the definition and
      clinical features are still unclear. The lack of precision has hampered the
      establishment of guidelines for the management of asymptomatic MMD. The purpose
      of this study was to define and clarify the clinical characteristics of
      asymptomatic MMD in adults. METHODS: We identified all adults (aged >=18 years)
      with MMD who underwent digital subtraction angiography or magnetic resonance
      angiography at our institution from 1995 through 2010. The authors defined
      asymptomatic MMD as asymptomatic or nonspecific symptom without any infarction or
      ischemia on magnetic resonance imaging. In our MMD registry, 40 patients (74
      hemispheres) were identified and enrolled in this retrospective cohort study.
      Their demographic, radiological and clinical findings were evaluated. The log
      rank test was used to assess prognostic factors. Pearson's correlation test and
      the Mann-Whitney U test were used to identify correlation angiographic staging
      and age or perfusion status. RESULTS: Overall, 6 patients underwent indirect
      bypass surgery and 36 received antiplatelet medication. On initial single
      positron emission tomography (35 patients, 67 affected hemispheres), basal and
      acetazolamide stress brain perfusion were decreased in 19 (28.4%) and 22 (32.8%)
      hemispheres, respectively. Among 70 angiographically evaluated hemispheres, 6
      were unilateral MMD; 27 of 64 affected hemispheres (42.2%) had transdural
      collateral at evaluation. Age (p = 0.309, Pearson's correlation test) and
      hemodynamic impairment (p = 0.614, Mann-Whitney U test) did not correlate with
      angiographic staging. During a median 32-month (range 6-203) clinical follow-up,
      3 nonsurgically treated patients had a transient ischemic attack, which was
      associated with decreased vascular reserve (p < 0.001, log-rank test) and smoking
      (p = 0.017). Other variables did not show a significant association with clinical
      progression. During a median 24-month (range 12-108) radiological follow-up, 3
      patients displayed angiographic progression and 3 displayed new hemodynamic
      abnormalities. Radiological progressions were related to hypertension only (p =
      0.022). In this case series, there was no case of ischemic or hemorrhagic stroke.
      CONCLUSION: The findings suggest that asymptomatic MMD in adults is not a stable
      disease in our definition. However, stroke rate (0%) was lower than previous
      reports. Lifestyle modification, stroke risk factor control and/or antiplatelet
      medication seem to be appropriate initial treatments for patients with normal
      cerebrovascular reserve. A clear definition of asymptomatic MMD and further
      clarification of its clinical course are needed to set precise treatment
      guidelines.

PMID- 24435044
TI  - Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self
      renewal.
AB  - Erythropoietin (EPO) is a hormone that induces red blood cell production. In its
      recombinant form, EPO is the one of most prescribed drugs to treat anemia,
      including that arising in cancer patients. In randomized trials, EPO
      administration to cancer patients has been associated with decreased survival.
      Here, we investigated the impact of EPO modulation on tumorigenesis. Using
      genetically engineered mouse models of breast cancer, we found that EPO promoted
      tumorigenesis by activating JAK/STAT signaling in breast tumor-initiating cells
      (TICs) and promoted TIC self renewal. We determined that EPO was induced by
      hypoxia in breast cancer cell lines, but not in human mammary epithelial cells.
      Additionally, we demonstrated that high levels of endogenous EPO gene expression
      correlated with shortened relapse-free survival and that pharmacologic JAK2
      inhibition was synergistic with chemotherapy for tumor growth inhibition in vivo.
      These data define an active role for endogenous EPO in breast cancer progression
      and breast TIC self-renewal and reveal a potential application of EPO pathway
      inhibition in breast cancer therapy. 

PMID- 24435046
TI  - Transplantation for children with acute myeloid leukemia: a comparison of
      outcomes with reduced intensity and myeloablative regimens.
AB  - The safety and efficacy of reduced-intensity conditioning (RIC) regimens for the
      treatment of pediatric acute myeloid leukemia is unknown. We compared the outcome
      of allogeneic hematopoietic cell transplantation in children with acute myeloid
      leukemia using RIC regimens with those receiving myeloablative-conditioning (MAC)
      regimens. A total of 180 patients were evaluated (39 with RIC and 141 with MAC
      regimens). Results of univariate and multivariate analysis showed no significant
      differences in the rates of acute and chronic graft-versus-host disease, leukemia
      free, and overall survival between treatment groups. The 5-year probabilities of
      overall survival with RIC and MAC regimens were 45% and 48%, respectively (P =
      .99). Moreover, relapse rates were not higher with RIC compared with MAC regimens
      (39% vs 39%; P = .95), and recipients of MAC regimens were not at higher risk for
      transplant-related mortality compared with recipients of RIC regimens (16% vs
      16%; P = .73). After carefully controlled analyses, we found that in this
      relatively modest study population, the data supported a role for RIC regimens
      for acute myeloid leukemia in children undergoing allogeneic hematopoietic cell
      transplantation. The data also provided justification for designing a carefully
      controlled randomized clinical trial that examines the efficacy of regimen
      intensity in this population. 

PMID- 24435048
TI  - In situ IR spectroscopic studies of Ni surface segregation induced by CO
      adsorption on Cu-Ni/SiO2 bimetallic catalysts.
AB  - It is of great importance to study the catalytic structures under real reaction
      conditions especially for the bimetallic catalysts, where facile surface
      restructure or surface segregation can be driven by adsorbate adsorption. Here,
      we report CO interaction with Cu-Ni/SiO2 bimetallic model catalysts studied by CO
      temperature programmed desorption (TPD) and in situ CO polarization modulation
      infrared reflection absorption spectroscopy (PM-IRRAS) under CO pressures varying
      from ultrahigh vacuum (UHV) to near ambient pressure. Under UHV conditions, Cu is
      enriched on the surface of Cu-Ni/SiO2 bimetallic catalysts. CO spillover from Cu
      to Ni on Cu-Ni/SiO2 bimetallic catalysts has been observed at about 200 K under
      UHV conditions. In situ CO PM-IRRAS shows surface segregation of Ni on the Cu
      Ni/SiO2 bimetallic catalysts induced by CO adsorption at ambient pressure CO. The
      behavior of CO induced surface segregation can lead to severe errors in Ni active
      site measurements by the selective CO chemisorption on Cu-Ni/SiO2 bimetallic
      catalysts. 

PMID- 24435047
TI  - Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8;
      and ARID1A underlying the pathogenesis of follicular lymphoma.
AB  - Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma
      in the western world. FL carries characteristic recurrent structural genomic
      aberrations. However, information regarding the coding genome in FL is still
      evolving. Here, we describe the results of massively parallel exome sequencing
      and single nucleotide polymorphism 6.0 array genomic profiling of 11 highly
      purified FL cases, and 1 transformed FL case and the validation of selected
      mutations in 102 FL cases. We report the identification of 15 novel recurrently
      mutated genes in FL. These include frequent mutations in the linker histone genes
      HIST1H1 B-E (27%) and mutations in OCT2 (also known as POU2F2; 8%), IRF8 (6%),
      and ARID1A (11%). A subset of the mutations in HIST1H1 B-E affected binding to
      DNMT3B, and mutations in HIST1H1 B-E and in EZH2 or ARID1A were largely mutually
      exclusive, implicating HIST1H1 B-E in epigenetic deregulation in FL. Mutations in
      OCT2 (POU2F2) affected its transcriptional and functional properties as measured
      through luciferase assays, the biological analysis of stably transduced cell
      lines, and global expression profiling. Finally, multiple novel mutated genes
      located within regions of acquired uniparental disomy in FL are identified. In
      aggregate, these data substantially broaden our understanding of the genomic
      pathogenesis of FL. 

PMID- 24435049
TI  - A stochastic model dissects cell states in biological transition processes.
AB  - Many biological processes, including differentiation, reprogramming, and disease
      transformations, involve transitions of cells through distinct states. Direct,
      unbiased investigation of cell states and their transitions is challenging due to
      several factors, including limitations of single-cell assays. Here we present a
      stochastic model of cellular transitions that allows underlying single-cell
      information, including cell-state-specific parameters and rates governing
      transitions between states, to be estimated from genome-wide, population-averaged
      time-course data. The key novelty of our approach lies in specifying latent
      stochastic models at the single-cell level, and then aggregating these models to
      give a likelihood that links parameters at the single-cell level to observables
      at the population level. We apply our approach in the context of reprogramming to
      pluripotency. This yields new insights, including profiles of two intermediate
      cell states, that are supported by independent single-cell studies. Our model
      provides a general conceptual framework for the study of cell transitions,
      including epigenetic transformations. 

PMID- 24435050
TI  - Metabolic syndrome and prostate abnormalities in male subjects of infertile
      couples.
AB  - No previous study has evaluated systematically the relationship between metabolic
      syndrome (MetS) and prostate-related symptoms and signs in young infertile men.
      We studied 171 (36.5 +/- 8.3-years-old) males of infertile couples. MetS was
      defined based on the National Cholesterol Education Program Third Adult Treatment
      Panel. All men underwent hormonal (including total testosterone (TT) and
      insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)),
      scrotal and transrectal ultrasound evaluations. Because we have previously
      assessed correlations between MetS and scrotal parameters in a larger cohort of
      infertile men, here, we focused on transrectal features. Prostate-related
      symptoms were assessed using the National Institutes of Health Chronic
      Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score
      (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic
      ordinal model, insulin levels increased as a function of MetS components (Wald =
      29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359,
      P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed.
      In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number
      of MetS components correlated negatively with normal sperm morphology (Wald =
      5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is
      a marker of prostate inflammation, with prostate total and transitional zone
      volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with
      arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture
      nonhomogeneity (hazard ratio (HR) = 1.87 (1.05-3.33), P < 0.05), with
      calcification size (Wald = 3.11, P< 0.05), but not with parameters of seminal
      vesicle size or function. In conclusion, in males of infertile couples, MetS is
      positively associated with prostate enlargement, biochemical (sIL8) and
      ultrasound-derived signs of prostate inflammation but not with prostate-related
      symptoms, which suggests that MetS is a trigger for a subclinical, early-onset
      form of benign prostatic hyperplasia.

PMID- 24435051
TI  - More attention should be paid to the treatment of male infertility with drugs-
      testosterone: to use it or not?

PMID- 24435052
TI  - Testosterone deficiency: a historical perspective.
AB  - The biological effects of the testes and testosterone are known since antiquity.
      Aristotle knew the effects of castration and his hypothesis on fertilization is
      one of the first scientific encounters in reproductive biology. Over centuries,
      castration has been performed as punishment and to produce obedient slaves, but
      also to preserve the soprano voices of prepubertal boys. The Chinese imperial
      (and other oriental) courts employed castrates as overseers in harems who often
      obtained high-ranking political positions. The era of testis transplantation and
      organotherapy was initiated by John Hunter in London who transplanted testes into
      capons in 1786. The intention of his experiments was to prove the 'vital
      principle' as the basis for modern transplantation medicine, but Hunter did not
      consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion
      from his testicular transplantation experiments in 1849 in Gottingen and is thus
      considered the father of endocrinology. Following his observations, testicular
      preparations were used for therapy, popularized by self-experiments by Charles
      Edouard Brown-Sequard in Paris (1889), which can at best have placebo effects. In
      the 1920s Sergio Voronoff transplanted testes from animals to men, but their
      effectiveness was disproved. Today testicular transplantation is being refined by
      stem cell research and germ cell transplantation. Modern androgen therapy started
      in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam.
      In the same year testosterone was chemically synthesized independently by Adolf
      Butenandt in Gottingen and Leopold Ruzicka in Basel. Since testosterone was
      ineffective orally it was either compressed into subcutaneous pellets or was used
      orally as 17alpha-methyl testosterone, now obsolete because of liver toxicity.
      The early phases of testosterone treatment coincide with the first description of
      the most prominent syndromes of hypogonadism by Klinefelter, by Kallmann,
      DelCastillo and Pasqualini. In the 1950s longer-acting injectable testosterone
      enanthate became the preferred therapeutic modality. In the 1950s and 1960s,
      research concentrated on the chemical modification of androgens in order to
      emphasize their anabolic effects. Although anabolic steroids have largely
      disappeared from clinical medicine, they continue to live an illegal life for
      doping in athletics. In the 1970s the orally effective testosterone undecanoate
      was added to the spectrum of preparations. Recent transdermal gels and long
      acting injectable preparations provide options for physiological testosterone
      substitution therapy.

PMID- 24435053
TI  - Long and noncoding RNAs (lnc-RNAs) determine androgen receptor dependent gene
      expression in prostate cancer growth in vivo.
AB  - Hyperactive androgen receptor (AR) activity remains a key determinant of the
      onset and progression of prostate cancer and resistance to current therapies. The
      mechanisms governing castrate resistant prostate cancer are poorly understood,
      but defining these molecular events is essential in order to impact deaths from
      prostate cancer. Yang et al. demonstrate that two lnc-RNAs known to be
      overexpressed in therapy resistant prostate cancer, PRNCR1 (also known as PCAT8)
      and PCGEM1, bound to the AR to enhance ligand-dependent and ligand-independent AR
      gene expression and proliferation of prostate cancer cells.1 The sequence of
      these interactions involved the binding of PRNCR1 to the acetylated AR and a
      subsequent association of DOT1L, which was required for the sequential
      recruitment of the lncRNA PCGEM1 to the AR amino terminus, which in turn was
      methylated by DOT1L.

PMID- 24435054
TI  - Tissue elasticity displayed by elastography and its correlation with the
      characteristics of collagen type I and type III in prostatic stroma.
AB  - We investigated the prostate elasticity displayed by elastography and its
      correlation with the content and distribution of collagen type I (Col1) and type
      III (Col3). A total of 62 patients underwent transrectal real-time tissue
      elastography (TRTE) examinations. Targeted biopsies were performed after 12-core
      systematic biopsy. The tissues corresponding to the elastograms were stained with
      picric acid-sirius red. The distribution of Col1 and type Col3 was observed, and
      the collagen volume fraction (CVF) of these two types of collagen fibers was
      calculated. The CVFs of Col1 in the stiff and soft groups were 0.05 +/- 0.02 and
      0.02 +/- 0.01 (P = 0.002), respectively. The CVFs of Col3 in the stiff and soft
      groups were 0.05 +/- 0.04 and 0.07 +/- 0.03 (P = 0.13), respectively. The
      circular analysis results showed that collagen fibers were disorganized both in
      the soft and stiff groups. Col1 and Col3 were mainly cross-linked, and some
      parallelization was observed in the sections. The distributions of Col1 and Col3
      were different between the stiff and soft groups (P = 0.03). In conclusion, the
      texture of the prostate is due to the content of Col1 and its relative
      correlation with Col3.

PMID- 24435055
TI  - Immunotherapy and therapeutic vaccines in prostate cancer: an update on current
      strategies and clinical implications.
AB  - In recent years, immunotherapy has emerged as a viable and attractive strategy
      for the treatment of prostate cancer. While there are multiple ways to target the
      immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have
      been most successful in late-stage clinical trials. The landmark Food and Drug
      Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic
      metastatic prostate cancer set the stage for ongoing phase III trials with the
      cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A
      common feature of these immune-based therapies is the appearance of improved
      overall survival without short-term changes in disease progression. This class
      effect appears to be due to modulation of tumor growth rate kinetics, in which
      the activated immune system exerts constant immunologic pressure that slows net
      tumor growth. Emerging data suggest that the ideal population for clinical trials
      of cancer vaccines is patients with lower tumor volume and less aggressive
      disease. Combination strategies that combine immunotherapy with standard
      therapies have been shown to augment both immune response and clinical benefit. 

PMID- 24435056
TI  - The relationship between sleep disorders and testosterone in men.
AB  - Plasma testosterone levels display circadian variation, peaking during sleep, and
      reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with
      pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing
      hormone (LH) secretion. The increase in testosterone is sleep, rather than
      circadian rhythm, dependent and requires at least 3 h of sleep with a normal
      architecture. Various disorders of sleep including abnormalities of sleep
      quality, duration, circadian rhythm disruption, and sleep-disordered breathing
      may result in a reduction in testosterone levels. The evidence, to support a
      direct effect of sleep restriction or circadian rhythm disruption on testosterone
      independent of an effect on sex hormone binding globulin (SHBG), or the presence
      of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive
      sleep apnea (OSA) appears to have no direct effect on testosterone, after
      adjusting for age and obesity. However, a possible indirect causal process may
      exist mediated by the effect of OSA on obesity. Treatment of moderate to severe
      OSA with continuous positive airway pressure (CPAP) does not reliably increase
      testosterone levels in most studies. In contrast, a reduction in weight does so
      predictably and linearly in proportion to the amount of weight lost. Apart from a
      very transient deleterious effect, testosterone treatment does not adversely
      affect OSA. The data on the effect of sleep quality on testosterone may depend on
      whether testosterone is given as replacement, in supratherapeutic doses, or in
      the context abuse. Experimental data suggest that testosterone may modulate
      individual vulnerability to subjective symptoms of sleep restriction. Low
      testosterone may affect overall sleep quality which is improved by replacement
      doses. Large doses of exogenous testosterone and anabolic/androgenic steroid
      abuse are associated with abnormalities of sleep duration and architecture.

PMID- 24435057
TI  - Bone targeted therapies for the prevention of skeletal morbidity in men with
      prostate cancer.
AB  - Men with prostate cancer suffer substantially from bone-related complications.
      Androgen deprivation therapy itself is a cause of loss of bone mineral density
      and is associated with an increased incidence of osteoporotic fractures. In
      advanced disease, bone is by far the most common site of metastasis.
      Complications of bone metastases prominently include pain and the potential for
      skeletal events such as spinal cord compression and pathologic fractures.
      Elevated osteoclast activity is an important aspect of the pathophysiology of
      both treatment-related osteoporosis and skeletal complications due to metastases.
      The osteoclast is therefore a therapeutic target. Denosumab is a fully human
      monoclonal antibody to receptor activator of nuclear factor-kappa-B ligand that
      was designed to potently inhibit osteoclast activity and is the central focus of
      this review. Bisphosphonates, radiopharmaceuticals and systemically-active
      hormonal agents such as abiraterone acetate and enzalutamide have each been shown
      to improve skeletal morbidity in specific clinical situations. Denosumab is the
      only agent that has been shown to prevent osteoporotic fractures in men receiving
      androgen deprivation therapy and at elevated risk for fracture. It has also
      demonstrated superiority to the potent bisphosphonate zoledronic acid for the
      prevention of skeletal-related events in men with castration-resistant prostate
      cancer metastatic to bone. Efficacy and toxicity data will be discussed. 

PMID- 24435059
TI  - On-chip plasmon-induced transparency based on plasmonic coupled nanocavities.
AB  - On-chip plasmon-induced transparency offers the possibility of realization of
      ultrahigh-speed information processing chips. Unfortunately, little experimental
      progress has been made to date because it is difficult to obtain on-chip plasmon
      induced transparency using only a single meta-molecule in plasmonic circuits.
      Here, we report a simple and efficient strategy to realize on-chip plasmon
      induced transparency in a nanoscale U-shaped plasmonic waveguide side-coupled
      nanocavity pair. High tunability in the transparency window is achieved by
      covering the pair with different organic polymer layers. It is possible to
      realize ultrafast all-optical tunability based on pump light-induced refractive
      index change of a graphene cover layer. Compared with previous reports, the
      overall feature size of the plasmonic nanostructure is reduced by more than three
      orders of magnitude, while ultrahigh tunability of the transparency window is
      maintained. This work also provides a superior platform for the study of the
      various physical effects and phenomena of nonlinear optics and quantum optics. 

PMID- 24435058
TI  - Chemotherapy and its evolving role in the management of advanced prostate cancer.
AB  - Advanced prostate cancer has been recognized as being responsive to androgen
      deprivation since the 1940s when Charles Huggins first described the role of
      surgical castration in managing these patients. However, androgen deprivation
      only results in transient disease control for the vast majority of men, with
      those progressing in spite of castrate testosterone levels labeled as having
      castrate-resistant prostate cancer (CRPC). Until 2004, the therapeutic arena for
      these patients had remained stagnant, with no agent having shown a survival gain
      in the CRPC setting. Two landmark publications changed the prostate cancer
      treatment landscape by providing 'level-1 evidence' that docetaxel-based
      chemotherapy led to prolongation in overall survival (OS). This was followed by
      the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating
      its efficacy in patients pretreated with docetaxel. More recently, a number of
      next-generation androgen-directed agents (e.g. abiraterone and enzalutamide) have
      also been shown to lead to a survival benefit in men with CRPC. With so many new
      treatment options available, a number of questions remain. These include: how to
      best sequence chemotherapy with these newer hormonal agents, the clinical
      implication of cross-resistance between taxanes and androgen-directed agents and
      which subsets of patients may benefit most from early use of chemotherapy. This
      review will provide an overview of the evolving role of chemotherapy in the
      management of advanced prostate cancer in the current era. 

PMID- 24435060
TI  - Phase I study of anti-VEGF monoclonal antibody bevacizumab and histone
      deacetylase inhibitor valproic acid in patients with advanced cancers.
AB  - PURPOSE: Anti-angiogenic agents combined with histone deacetylase inhibitors act
      synergistically in vitro and in vivo. We conducted a phase I study of the
      combination of the anti-VEGF monoclonal antibody bevacizumab and histone
      deacetylase inhibitor valproic acid in patients with advanced cancers. METHODS:
      Bevacizumab was administered at escalating dosages of 2.5-11 mg/kg on days 1 and
      15, and oral valproic acid at dosages of 5.3-10 mg/kg on days 1-28 every 28 days
      to determine the maximum tolerated dose. Pharmacodynamic parameters were assessed
      in peripheral blood mononuclear cells (histone H3 acetylation) and serum
      (valproic acid levels). RESULTS: Fifty-seven patients were enrolled. Dose
      limiting toxicities were grade 3 altered mental status (n = 2), related to
      valproic acid. Bevacizumab 11 mg/kg given on days 1 and 15 and valproic acid 5.3
      mg/kg daily were the recommended phase II dosages. Stable disease (SD) >=6 months
      was reported in 4/57 (7 %) of patients, including two patients with colorectal
      cancer who had progressed previously on bevacizumab. Of the 39 patients evaluated
      for histone acetylation, 2 of 3 (67 %) patients with SD >=6 months showed histone
      acetylation, while 8 of 36 (22 %) without SD >=6 months demonstrated histone
      acetylation (p = 0.16). Patients with any grade of hypertension, compared to
      others, had a prolonged median survival (11.1 vs. 5.8 months; p = 0.012).
      CONCLUSIONS: The combination of bevacizumab 11 mg/kg and valproic acid 5.3 mg/kg
      is safe in patients with advanced malignancies, with activity in colorectal,
      gastroesophageal junction, and prostate cancer. Patients with hypertension had
      improved overall survival.

PMID- 24435061
TI  - Global architecture of the F-actin cytoskeleton regulates cell shape-dependent
      endothelial mechanotransduction.
AB  - Uniaxial stretch is an important biophysical regulator of cell morphology (or
      shape) and functions of vascular endothelial cells (ECs). However, it is unclear
      whether and how cell shape can independently regulate EC mechanotransductive
      properties under uniaxial stretch. Herein, utilizing a novel uniaxial cell
      stretching device integrated with micropost force sensors, we reported the first
      experimental evidence showing cell shape-dependent EC mechanotransduction via
      cytoskeleton (CSK) contractile forces in response to uniaxial stretch. Combining
      experiments and theoretical modeling from first principles, we showed that it was
      the global architecture of the F-actin CSK that instructed the cell shape
      dependent EC mechanotransductive process. Furthermore, a cell shape-dependent
      nature was relayed in EC mechanotransduction via dynamic focal adhesion (FA)
      assembly. Our results suggested a novel mechanotransductive process in ECs
      wherein the global architecture of the F-actin CSK, governed by cell shape,
      controls mechanotransduction via CSK contractile forces and force-dependent FA
      assembly under uniaxial stretch. 

PMID- 24435062
TI  - Distinct structural features of TFAM drive mitochondrial DNA packaging versus
      transcriptional activation.
AB  - TFAM (transcription factor A, mitochondrial) is a DNA-binding protein that
      activates transcription at the two major promoters of mitochondrial DNA (mtDNA)-
      the light strand promoter (LSP) and the heavy strand promoter 1 (HSP1). Equally
      important, it coats and packages the mitochondrial genome. TFAM has been shown to
      impose a U-turn on LSP DNA; however, whether this distortion is relevant at other
      sites is unknown. Here we present crystal structures of TFAM bound to HSP1 and to
      nonspecific DNA. In both, TFAM similarly distorts the DNA into a U-turn. Yet,
      TFAM binds to HSP1 in the opposite orientation from LSP explaining why
      transcription from LSP requires DNA bending, whereas transcription at HSP1 does
      not. Moreover, the crystal structures reveal dimerization of DNA-bound TFAM. This
      dimerization is dispensable for DNA bending and transcriptional activation but is
      important in DNA compaction. We propose that TFAM dimerization enhances
      mitochondrial DNA compaction by promoting looping of the DNA.

PMID- 24435063
TI  - Interest and informational preferences regarding genomic testing for modest
      increases in colorectal cancer risk.
AB  - BACKGROUND/AIMS: This study explored the interest in genomic testing for modest
      changes in colorectal cancer risk and preferences for receiving genomic risk
      communications among individuals with intermediate disease risk due to a family
      history of colorectal cancer. METHODS: Surveys were conducted on 272 men and
      women at intermediate risk for colorectal cancer enrolled in a randomized trial
      comparing a remote personalized risk communication intervention (TeleCARE) aimed
      at promoting colonoscopy to a generic print control condition. Guided by
      Leventhal's Common Sense Model of Self-Regulation, we examined demographic and
      psychosocial factors possibly associated with interest in SNP testing.
      Descriptive statistics and logistic regression models were used to identify
      factors associated with interest in SNP testing and preferences for receiving
      genomic risk communications. RESULTS: Three-fourths of participants expressed
      interest in SNP testing for colorectal cancer risk. Testing interest did not
      markedly change across behavior modifier scenarios. Participants preferred to
      receive genomic risk communications from a variety of sources: printed materials
      (69.5%), oncologists (54.8%), primary-care physicians (58.4%), and the web
      (58.1%). Overall, persons who were unmarried (p = 0.029), younger (p = 0.003) and
      with greater cancer-related fear (p = 0.019) were more likely to express interest
      in predictive genomic testing for colorectal cancer risk. In a stratified
      analysis, cancer-related fear was associated with the interest in predictive
      genomic testing in the intervention group (p = 0.017), but not the control group.
      CONCLUSIONS: Individuals with intermediate familial risk for colorectal cancer
      are highly interested in genomic testing for modest increases in disease risk,
      specifically unmarried persons, younger age groups and those with greater cancer
      fear.

PMID- 24435064
TI  - Anal cytology and p16 immunostaining for screening anal intraepithelial neoplasia
      in HIV-positive and HIV-negative men who have sex with men: a cross-sectional
      study.
AB  - Summary Akin to cervical cancer in sexually-active women, men who have sex with
      men (MSM) are predisposed to anal cancers, especially those with HIV co
      infection. This cross-sectional study endeavored to assess the prevalence of anal
      dysplasia using Pap smears and p16 immunostaining amongst Indian MSM. A total of
      31 consecutive HIV-positive and 34 HIV-negative MSM, from a cohort of sexually
      transmitted infection clinic attendees, underwent anal cytological evaluation
      with Pap smear and p16 staining. Chi square test and coefficient of correlation
      were used for comparison. Eighteen (27.7%) had abnormal anal cytology; increased
      in HIV-positive as compared to HIV-negative men (35% versus 20%, p = 0.180).
      Similarly, both low-grade (25.8% versus 17.6%) and high-grade lesions (8.3%
      versus 4.8%) were comparable in HIV-positive and HIV-negative group. Thirteen
      (20%) smears were p16-positive with a sensitivity and specificity for anal
      dysplasia of 72.3% and 100%, respectively. Anal cytology may be used to screen
      for anal dysplasia in MSM irrespective of HIV status. Furthermore, the addition
      of p16, with greater specificity for high-grade lesions, may improve diagnostic
      accuracy especially for high-grade lesions. A larger study to further corroborate
      these observations is warranted. 

PMID- 24435065
TI  - Using ruthenium polypyridyl functionalized ZnO mesocrystals and gold nanoparticle
      dotted graphene composite for biological recognition and electrochemiluminescence
      biosensing.
AB  - Using ruthenium polypyridyl functionalized ZnO mesocrystals as bionanolabels, a
      universal biological recognition and biosensing platform based on gold
      nanoparticle (AuNP) dotted reduced graphene oxide (rGO) composite was developed.
      AuNP-rGO accelerated electron transfer between the detection probe and the
      electrode, and increased the surface area of the working electrode to load
      greater amounts of the capture antibodies. The large surface area of ZnO
      mesocrystals was beneficial for loading a high content ruthenium polypyridyl
      complex, leading to an enhanced electrochemiluminescence signal. Using alpha
      fetoprotein (AFP) as a model, a simple and sensitive sandwich-type
      electrochemiluminescence biosensor with tripropylamine (TPrA) as a coreactant for
      detection of AFP was constructed. The designed biosensor provided a good linear
      range from 0.04 to 500 ng mL(-1) with a low detection limit of 0.031 ng mL(-1) at
      a S/N of 3 for AFP determination. The proposed biological recognition and
      biosensing platform extended the application of ruthenium polypyridyl
      functionalized ZnO mesocrystals, which provided a new promising prospect. 

PMID- 24435066
TI  - Clinical study of the visual field defects caused by occipital lobe lesions.
AB  - BACKGROUND: The central visual field is projected to the region from the
      occipital tip to the posterior portion of the medial area in the striate cortex.
      However, central visual field disturbances have not been compared with the
      location of the lesions in the striate cortex. METHODS: Thirteen patients with
      visual field defects caused by partial involvement of the striate cortex were
      enrolled. The lesions were classified according to their location into the
      anterior portion, the posterior portion of the medial area, and the occipital
      tip. Visual field defects were examined by the Goldmann perimetry, the Humphrey
      perimetry and the auto-plot tangent screen. We defined a defect within the
      central 10 degrees  of vision as a central visual field disturbance. The visual
      field defects in 13 patients were compared with the location of their lesions in
      the striate cortex. RESULTS: The medial area was involved in 7 patients with no
      involvement of the occipital tip. In 2 of them, peripheral homonymous hemianopia
      without central visual field disturbance was shown, and their lesions were
      located only in the anterior portion. One patient with a lesion in the posterior
      portion alone showed incomplete central homonymous hemianopia. Three of 4
      patients with lesions located in both the anterior and posterior portions of the
      medial area showed incomplete central homonymous hemianopia and peripheral
      homonymous hemianopia. The occipital tip was involved in 6 patients. Five of them
      had small lesions in the occipital tip alone and showed complete central
      homonymous hemianopia or quadrantanopia. The other patient with a lesion in the
      lateral posterior portion and bilateral occipital tip lesions showed bilateral
      slight peripheral visual field disturbance in addition to complete central
      homonymous hemianopia on both sides. CONCLUSIONS: Lesions in the posterior
      portion of the medial area as well as the occipital tip caused central visual
      field disturbance in our study, as indicated in previous reports. Central
      homonymous hemianopia tended to be incomplete in patients with lesions in the
      posterior portion in the medial area. In contrast, complete central homonymous
      hemianopia and quadrantanopia were shown in patients with occipital tip lesions.
      Our study suggested that the fibers related to the central visual field were
      sparse in the posterior portion of the medial area in contrast to the occipital
      tip, and approached the occipital tip with a high concentration of fibers.

PMID- 24435067
TI  - Glucose metabolism in the primary auditory cortex of postlingually deaf patients:
      an FDG-PET study.
AB  - BACKGROUND/PURPOSE: Previous FDG-PET studies have indicated neuroplasticity in
      the adult auditory cortex in cases of postlingual deafness. In the mature brain,
      auditory deprivation decreased neuronal activity in primary auditory and auditory
      related cortices. In order to reevaluate these issues, we used statistical
      analytic software, namely a three-dimensional stereotaxic region of interest
      template (3DSRT), in addition to statistical parametric mapping (SPM; Institute
      of Neurology, University College of London, UK). MATERIALS AND METHODS: (18)F-FDG
      brain PET scans were performed on 7 postlingually deaf patients and 10 healthy
      volunteers. Significant increases and decreases of regional cerebral glucose
      metabolism in the patient group were estimated by comparing their PET images with
      those of healthy volunteers using SPM analysis and 3DSRT. RESULTS: SPM revealed
      that the glucose metabolism of the deaf patients was lower in the right superior
      temporal gyrus, both middle temporal gyri, left inferior temporal gyrus, right
      inferior lobulus parietalis, right posterior cingulate gyrus, and left insular
      cortex than that of the control subjects. 3DSRT data also revealed significantly
      decreased glucose metabolism in both primary auditory cortices of the
      postlingually deaf patients. CONCLUSION: SPM and 3DSRT analyses indicated that
      glucose metabolism decreased in the primary auditory cortex of the postlingually
      deaf patients. The previous results of PET studies were confirmed, and our method
      involving 3DSRT has proved to be useful.

PMID- 24435068
TI  - Effectiveness of bevacizumab for radiation-induced cerebral necrosis in children.
AB  - INTRODUCTION: Bevacizumab has been reported to effectively reduce cerebral edema
      caused by radiation therapy. However, only limited data with a short follow-up in
      tumor patients are available so far. PATIENTS AND METHODS: Two children suffering
      from hemorrhage from arteriovenous malformation (AVM) have been treated with
      stereotactic radiotherapy and developed radiation-induced cerebral edema with
      deteriorating neurological status despite maximized steroid therapy. Bevacizumab
      administration at 5 mg/kg body weight was initiated every 2 weeks. RESULTS:
      Bevacizumab treatment rapidly ameliorated the neurological deficits, malignant
      edema and prevented catastrophic complications. Corticoid therapy could be
      reduced and discontinued. However, after 18 months, both patients showed
      identical or worse neurological status than before bevacizumab therapy. AVM
      radiation therapy had been successful to completely obliterate AVMs. DISCUSSION:
      In our limited experience, bevacizumab may be an effective and safe option for
      rescue therapy for malignant cerebral edema on the basis of radiation-induced
      necrosis especially in patients who experience rapid deterioration despite
      corticoid therapy and/or intolerable steroid side effects. Despite the fact that
      functional improvement could not be achieved in long-term outcome patients
      significantly stabilized and improved during periods of acute deterioration. In
      order to determine the long-term effectiveness of bevacizumab further
      investigation in placebo-controlled studies with a higher number of patients are
      required.

PMID- 24435069
TI  - Development and evaluation of a leaflet containing shoe advice: a randomized
      controlled trial.
AB  - BACKGROUND: Providing advice to wear good quality shoes with appropriate fit is
      one of the possibilities GPs have when treating patients with foot problems.
      OBJECTIVES: The aims of this study are to (i) determine which shoe
      characteristics are important when providing shoe advice; (ii) develop a shoe
      advice leaflet and (iii) evaluate if women choose better shoes with the aid of
      the leaflet. METHODS: We performed a literature search on the effect of separate
      shoe characteristics on foot pathologies and kinematics and developed an
      information leaflet with the aid of multidisciplinary experts. The leaflet was
      tested in a group of women aged 50 years or over who did not receive podiatric
      treatment or shoe advice in the year prior to the study. The women were asked to
      select shoes; half of them were provided with the leaflet. Shoe characteristics
      were scored blinded for the condition by two podiatrists. Data were analysed
      using a t-test for independent measures. RESULTS: The developed leaflet contains
      nine shoe characteristics. A total of 57 women ranging from 54 to 86 years old
      (average 69) consented to participate in testing the efficacy of the leaflet.
      Women using the leaflet (n = 29) selected better shoes than without (P = 0.049).
      CONCLUSIONS: Based on a literature search and expert opinion, we have developed
      an information leaflet for GPs to provide as a supplement to oral shoe advice.
      Women using this leaflet were able to select shoes of better quality and better
      fit than women selecting shoes without using the leaflet.

PMID- 24435070
TI  - Selenite reduction by Shewanella oneidensis MR-1 is mediated by fumarate
      reductase in periplasm.
AB  - In situ reduction of selenite to elemental selenium (Se(0)), by microorganisms in
      sediments and soils is an important process and greatly affects the environmental
      distribution and the biological effects of selenium. However, the mechanism
      behind such a biological process remains unrevealed yet. Here we use Shewanella
      oneidensis MR-1, a widely-distributed dissimilatory metal-reducing bacterium with
      a powerful and diverse respiration capability, to evaluate the involvement of
      anaerobic respiration system in the microbial selenite reduction. With mutants
      analysis, we identify fumarate reductase FccA as the terminal reductase of
      selenite in periplasm. Moreover, we find that such a reduction is dependent on
      central respiration c-type cytochrome CymA. In contrast, nitrate reductase,
      nitrite reductase, and the Mtr electron transfer pathway do not work as selenite
      reductases. These findings reveal a previously unrecognized role of anaerobic
      respiration reductases of S. oneidensis MR-1 in selenite reduction and
      geochemical cycles of selenium in sediments and soils. 

PMID- 24435072
TI  - Homologous size-extension of hybrid vanadate capsules - solid state structures,
      solution stability and surface deposition.
AB  - The dimensions and cavity sizes of the molecular capsules with the general
      formula [V10O18L4](10-) can be controlled modularly through the nature of the
      bifunctional, rigid organophosphonate ligands L(1) and L(2) (L(1) = bis(4
      phosphonatophenyl)ethyne and L(2) = bis(4-phosphonatophenyl)butadiyne); the
      solution stability of the molecular entities as demonstrated by ESI-MS studies
      permits their assembly on the Au(111) surface on a sub-monolayer scale giving
      rise to a 2D supramolecular structure that is comparable to the packing
      arrangements of the capsules in the crystal structures. 

PMID- 24435071
TI  - Intrinsic hippocampal activity as a biomarker for cognition and symptoms in
      schizophrenia.
AB  - OBJECTIVE: Identification of biomarkers for cognitive dysfunction in
      schizophrenia is a priority for psychiatry research. Functional imaging studies
      suggest that intrinsic "resting state" hippocampal hyperactivity is a
      characteristic feature of schizophrenia. The relationships between this phenotype
      and symptoms of the illness, however, are largely unexplored. The authors
      examined resting hippocampal activity in schizophrenia patients and healthy
      comparison subjects and analyzed the relationship between intrinsic hippocampal
      activity and cognitive function in patients as measured by the MATRICS Consensus
      Cognitive Battery (MCCB). METHOD: Twenty-eight schizophrenia patients and 28 age
      matched healthy comparison subjects underwent functional "resting state" 3-T MR
      scanning. Hippocampal activity was extracted by group independent component
      analysis. Correlation analyses were used to examine the relationship between
      hippocampal activity and MCCB composite and domain scores in patients, as well as
      between hippocampal activity and positive and negative symptoms. RESULTS: Greater
      activity of the right hippocampus at rest was observed in patients relative to
      comparison subjects. In patients, a significant negative correlation was observed
      between right hippocampal activity and composite MCCB T-score. The correlation
      was driven by the MCCB domains of attention/vigilance, working memory, and visual
      learning. Hippocampal activity was positively correlated with negative symptoms.
      MCCB scores were inversely correlated with negative symptoms. CONCLUSIONS: These
      findings suggest that greater intrinsic hippocampal activity is a characteristic
      feature of schizophrenia that is broadly associated with cognitive dysfunction,
      and they support hippocampal activity as a candidate biomarker for therapeutic
      development.

PMID- 24435073
TI  - Substitution and compensation Erode the energy deficit from exercise
      interventions.

PMID- 24435074
TI  - Response.

PMID- 24435075
TI  - Notice of redundant publication: Dynamic visual acuity in baseball players is due
      to superior tracking abilities.

PMID- 24435076
TI  - Organ donation as an 'altruistic gift': incentives and reciprocity in deceased
      organ donation from a UK Polish migrant perspective.
AB  - BACKGROUND: Incentives and reciprocity have been widely debated within the
      literature as an alternative to altruism to motivate the public to register and
      consent to organ donation. This pilot study was the first to examine the views of
      the UK Polish migrant community toward these issues. MATERIAL/METHODS: One-to-one
      and small group interviews were conducted in English and Polish to collect data.
      The interviews were recorded and transcribed and interviews in Polish were
      translated into English. All transcripts were coded, codes were grouped by theme
      and emergent themes were constantly compared to the new data until saturation.
      RESULTS: Participants were motivated to donate altruistically but would accept
      reciprocity for organs once consent was given. Payment for organs was viewed as
      unfavourable but participants would accept contribution toward funeral expenses.
      CONCLUSIONS: Deceased organ donation was viewed as an 'altruistic gift'.
      'Altruism' and 'gift' are problematic in deceased organ donation and could
      explain the challenges that arise in the incentives and reciprocity debate.
      Mauss's gift exchange theory could frame incentives as forming the 'obligation to
      give' and could encourage registration but could lead to coercion. Reciprocity
      could benefit families and be viewed as 'fair' and a token of gratitude.

PMID- 24435077
TI  - Histochemistry and fine structure of developing wheat aleurone cells.
AB  - Developing aleurone cells can first be distinguished 10 days after anthesis
      beneath the degenerating nucellus as somewhat cuboidal cells with extremely thin
      walls and large nuclei. Ribosomes are very abundant but little endoplasmic
      reticulum (ER) is apparent. By 14 days the cell walls are intensely
      autofluorescent, possibly due to the presence of a ferulic acid-carbohydrate
      complex. At this stage the cytoplasm is characterized by the presence of large
      vacuoles, many of which contain small, electron-dense inclusions, presumably the
      beginnings of the phytin globoids (Type I inclusions) of mature aleurone grains.
      The paired appearance of many of the cells suggests that they are dividing
      periclinally, the innermost cells destined to become part of the starchy
      endosperm. By 4 weeks the cell walls have greatly thickened, ER and mitochondria
      have proliferated, and the vacuoles, which subsequently give rise to mature
      aleurone grains, contain a second type of inclusion (Type II inclusion) embedded
      in a protein matrix. Although the walls remain uniformly autofluorescent, an
      intensely stained inner wall can be distinguished readily from the outer wall. By
      5 weeks the aleurone grains are almost completely surrounded by lipid droplets
      and contain numerous Type I inclusions. The cells change little in appearance
      from 6 weeks to maturity. At the latter stage the inner and outer walls are quite
      distinct and the cytoplasm is densely packed with aleurone grains which are
      completely surrounded by lipid droplets and interspersed with occasional plastids
      and numerous mitochondria with rather indistinct cristae. 

PMID- 24435078
TI  - Stoichiometry between photosynthetic nitrate reduction and alkalinisation by
      Ankistrodesmus braunii in vivo.
AB  - The uptake of nitrate or nitrite in the light, the release of nitrite and
      ammonia, and the corresponding alkalinisation of the medium were measured in
      synchronous Ankistrodesmus braunii (Naeg.) Brunnth. The increase in the OH(-)
      concentration in the medium reflects a stoichiometric ratio between OH(-) and NO3
      (-) of 1.3-1.8 in air, reaching almost 2.0 in CO2-free air or nitrogen. At low
      CO2 concentrations a large proportion of the nitrogen taken up as nitrate is
      released as ammonia, much less as nitrite. The stoichiometry of alkalinisation
      and NO3 (-) or NO2 (-) uptake can be quantitatively explained by assuming: 1) a
      counter-transport, at a ratio of 1:1, of OH(-) against NO3 (-) at the plasmalemma
      and of OH(-) against NO2 (-) at the chloroplast envelope, and 2) a co-transport
      of 1:1 of OH(-) and NH4 (+) to the medium through both membranes. The first OH(-)
      required is formed by proton consumption in nitrite reduction, the second OH(-)
      by proton consumption in the formation of NH4 (+) ions. Transport of K(+), Na(+)
      and Ca(2+) is not or only scarcely involved. This proposed transport system could
      provide charge equilibrium between inside and outside the cells and could enable
      the cells to avoid nternal pH changes in nitrate and nitrite reduction. 

PMID- 24435079
TI  - Changes in activity of lysosomal ribonuclease following mechanical damage to
      leaves of Solanum tuberosum L.
AB  - Differential centrifugation experiments showed that the 13-fold increase in total
      acid ribonuclease (RNase) activity arising during the 48 h following mechanical
      damage to potato leaves was associated, in about equal proportions, with the
      sedimentable and supernatant fluid fractions of cell homogenates. Density
      gradient ultracentrifugation techniques revealed that the majority of the
      particulate activity of RNase was located in the lysosomal fraction of leaf
      homogenates. Although [(14)C]leucine was incorporated into leaf lysosomes during
      incubation following mechanical damage the various molecular forms of RNase
      purified from the organelles, one of which had a specific lysosomal location,
      contained negligible radioisotope. That form of the enzyme which did incorporate
      [(14)C]leucine was one of those confined to the supernatant fluid fraction of
      leaves.In addition to the massive quantitative changes in RNase activity which
      occurred subsequent to mechanical damage, extensive qualitative changes occurred
      in the complement of molecular forms of lysosomal RNase. The possible origins of
      these changes are discussed. 

PMID- 24435080
TI  - Correlative inhibition of lateral bud growth in Phaseolus vulgaris L. timing of
      bud growth following decapitation.
AB  - On intact, 3-week-old plants of Phaseolus the larger bud in the axils of the
      primary leaves shows slow, continuous elongation growth. Release from correlative
      inhibition can be detected within 30 min following decapitation. When 0.1%
      indoleacetic acid in lanolin is applied to the decapitated stem stump, the
      lateral bud shows slow growth during the first 7 h, then stops completely for a
      further 15 h but after 2 days a further gradual increase in length is
      observed.The movement of (14)C-labelled assimilates from the subtending primary
      leaf into the lateral bud increases following removal of the shoot apex. When
      indole acetic acid is applied to decapitated plants the ability of the buds to
      import (14)C increases for 5-7 h and then declines to a negligible amount. Little
      or no radioactivity from tritiated indoleacetic acid is transported into the
      lateral buds of decapitated plants during the first 48 h following removal of the
      apex and it appears that rapid metabolism of the compound occurs in the stem
      tissues. 

PMID- 24435081
TI  - Lamellar superoxide dismutase of isolated chloroplasts.
AB  - Photooxidation of hydroxylamine to nitrite by spinach (Spinacia oleracea L. and
      sugarbeet (Beta vulgaris L.) chloroplast lamellae in the presence of autoxidable
      electron acceptors is inhibited by either solubilized or membrane-bound
      superoxide dismutase (SOD). This inhibition is reversed by KCN. The rates of
      hydroxylamine photooxidation by chloroplast lamellae, a reaction which is
      apparently driven by the superoxide free-radical ion, was used for quantitating
      the amount of SOD bound to chloroplast lamellae, as compared to a soluble enzyme
      of defined concentration. After digitonin fragmentation of chloroplast lamellae,
      ca. 80% of the SOD activity is associated with subchloroplast particles
      sedimenting after 2 h centrifugation at 200 000 x g. Less than 10% of the SOD
      activity is associated with particles sedimenting after centrifugation for 30 min
      at 20 000 x g. 5-10% of the cyanide-sensitive SOD is recovered in the soluble
      fraction of the subchloroplast-free supernatant after centrifugation at 200 000 x
      g for 2 h. 

PMID- 24435082
TI  - [Growth of axillary buds of Salix babylonica L. and activity of phenylalanine
      ammonia-lyase].
AB  - In-vitro study of the growth of the axillary bud of a decapitated willow cutting
      gave the following results: 1. The intact and the decapitated willow cutting show
      a gradient of PAL (phenylalanine ammonia-lyase EC. 4.3.1.5) activity, which
      decreases from the apical part down to the base. 2. After decapitation of the
      cutting, a shift of PAL activity takes place 36 hr later at the section level. 3.
      A correlation between the growth of the axillary bud of the decapitated willow
      cutting and the PAL activity at the same level, within the stem as well as the
      leaf, has been demonstrated. In continuous red light (660 nm) apical dominance is
      lost after decapitation of the cutting.The highest leaf bud starts growing and
      replaces the cut-out apical bud. The PAL activity at that level first increases,
      then becomes stable.In continuous blue light (440 nm), apical dominance is
      maintained in spite of decapitation.The growth of the axillary bud is negligible
      and the PAL activity at that same level rapidly tends to zero. 

PMID- 24435083
TI  - Compositional changes in developing rape seed (Brassica napus L.).
AB  - The growth and composition of siliquas and seeds of oilseed rape was followed
      over 12 weeks from shortly after anthesis to maturity. Each plant produced 220
      siliquas, this number being constant throughout development. Seed numbers per
      siliqua fell from 19 to 9 by week 5 and declined to 7 at maturity. Hull(1) and
      seed growth followed a sigmoid pattern, but were not in phase. Seed development
      could be divided into 3 phases: In Phase 1, seed weight was low and starch and
      ethanol soluble compounds accounted for 80% DM. Phase 2, seed growth increased
      and storage oil and proteins were deposited accounting for 40% and 20% DM
      respectively at the end of this stage. Starch, glucose and fructose were utilized
      in this process. Phase 3 was largely concerned with the deposition of oil and
      protein in fixed proportions. Seed weight more than doubled while DM composition
      remained constant. Sugars were transferred from the hull to the seed to support
      this growth.The proportion of hull lipids remained constant throughout
      development until shortly before maturity when MGDG and DGDG fell due to
      chloroplast breakdown as indicated by chlorophyll disappearance. The FA
      composition of the hull lipids resembled that of photosynthetic tissue. In the
      seeds, the neutral lipids increased from 20% of the total lipids in Phase 1 to
      93% at maturity. The proportion of structural lipids declined as the storage
      lipids increased. In Phase 1 the FA composition of the lipid resembled that of
      photosynthetic tissue (high in C16:0; C18:2; C18:3). In Phase 2, FA typical of
      storage triglycerides (C20:1; C22:1, appeared, C18:1 transitorily increased, but
      C18:2 and C18:3 fell dramatically. In Phase 3, the content of C22:1 continued to
      rise, but the proportions of the other FA remained constant. 

PMID- 24435084
TI  - Photosynthesis and the induction of nitrate reductase and nitrite reductase in
      bean leaves.
AB  - In laaves of Phaseolus vulgaris L. cv. Prelude, the light-induced increase in
      activity of NADH-nitrate oxidoreductase (E.C.1.6.6.2; NAR) and reduced
      benzylviologennitrite oxidoreductase (E.C.1.6.6.4; NIR) starts at a certain stage
      in the development of the chloroplasts. In leaves with completely developed
      chloroplasts, a higher increase in activity of NAR and NIR is observed, after
      induction by the addition of nitrate, in the light than in the dark. DCMU
      inhibits the increase in activity of the two enzymes in the light. Both in the
      light in the presence of DCMU, and in the dark the increase in activity reaches a
      higher level by the addition of sucrose.Induction of NAR, but not of NIR, can be
      observed in excised etiolated leaves. No induction is found in leaves of intact
      etiolated seedlings.The relation between photosynthetic reactions and the
      increase in activity of NAR and NIR is discussed. It is suggested that NADH,
      indirectly formed by photosynthesis, protects NAR and affects in this way the
      balance between synthesis and breakdown of the enzyme. The increase in activity
      of NIR is possibly influenced by the presence of reduced ferredoxin. 

PMID- 24435085
TI  - Temperature effects on the carbon-isotope ratio of C3, C 4 and crassulacean-acid
      metabolism (CAM) plants.
AB  - The temperature coefficient of the delta(13)C value over the temperature range 14
      to 40 degrees  has been measured for plants with different photosynthetic
      pathways. C3 plants (6 species) had a temperature coefficient of-0.01250/00/(o),
      C3 plants (5 species)-0.0460/00/(o), "C4-like" CAM (2 species)-0.130/00/(o) and
      "C3-like" CAM (2 species)-0.0190/00/(o). The relative temperature insensitivity
      of the delta(13)C value is in contrast with the measured temperature dependence
      of delta(13)C values for ribulose-diphosphate carboxylase in vitro, and to the
      temperature response of photosynthesis. The temperature sensitivity of the "C4
      like" CAM plants was the relatively greatest; this is consistent with the
      evidence that high night temperature inhibits dark CO2 fixation. The same
      inhibition may occur in the "C3-like" CAM plants but it would not have as
      significant an effect on the delta(13)C value as these plants are primarily
      dependent on primary fixation of exogenous CO2 via the ribulose-diphosphate
      carboxylase reaction. 

PMID- 24435086
TI  - Non-transmissible and long-lasting effects of exogenous gibberellin on floral
      morphology in the eggplant (Solanum melongena L.).
AB  - Effects of localized treatments with gibberellin on floral morphology and growth
      of eggplant were confined to the treated part of the plant and were not
      transmitted to other parts. Single applications caused strong and long-lasting
      effects, similar to those of repeated applications over a prolonged period. The
      data suggest that gibberellin induced a self-sustaining process in the apices of
      treated branches. 

PMID- 24435087
TI  - Simulation of a high- and low-affinity sugar-uptake system in Chlorella by a pH
      dependent change in the Km of the uptake system.
AB  - Chlorella vulgaris cells take up hexoses by a proton cotransport system.
      Depending of the pH of the medium either a high- or a low-affinity uptake system
      or both these systems can be observed. In the latter case the cells exhibit
      distinct biphasic uptake kinetics. 

PMID- 24435088
TI  - Plasmodesmata between mesophyll and bundle sheath cells in relation to the
      exchange of C4-acids.
AB  - In the C4 species Salsola kali L. the frequency of plasmodesmata in the wall
      between mesophyll and bundle sheath cells has been determined with great
      precision by the use of transmission and scanning electron microscopy. The
      frequency of 14*10(8) cm(-2) is rather high compared to values from other plant
      tissues, but if it is assumed that the postulated exchange of C4-acids occur in
      the desmotubulus of the plasmodesmata, the fraction of the mesophyll-bundle
      sheath interface occupied by plasmodesmatal pores is 10-10(2) times smaller than
      previously thought. 

PMID- 24435089
TI  - Light dependent promotion and inhibition of adventitious root formation by
      gibberellic acid.
AB  - Cuttings from plants of Pisum sativum L. cv. "Alaska" which had been grown at an
      irradiance of 16 W m(-2) formed a higher number of roots than cuttings from
      plants grown at 38 W m(-2). (Irradiance during the rooting period always 16 W m(
      2).) High concentrations of gibberellic acid (GA3) inhibited rooting in cuttings
      from both types of stock plants. Low concentrations (10(-9)-10(-6) M) of GA3 were
      without effect in cuttings from plants irradiated with 38 W m(-2), but promoted
      rooting when the stock plants had been grown at 16 W m(-2). 

PMID- 24435090
TI  - Thin film fabricated from solution-dispersible porous hyperbranched conjugated
      polymer nanoparticles without surfactants.
AB  - Porous hyperbranched conjugated polymer nanoparticles with an average particle
      size of 20-60 nm and a specific surface area of 225 m(2) g(-1) have been prepared
      through Suzuki polymerization in a miniemulsion, which could be stably dispersed
      in common organic solvents after complete removal of surfactants. Furthermore, a
      simple spin-coating method for the preparation of homogeneous transparent thin
      films of the nanoparticle has been developed. Bright blue emission of the porous
      nanoparticle films could be reversibly quenched by nitroaromatics with enhanced
      sensitivity compared to dense films of the linear conjugated polymer analogue. 

PMID- 24435091
TI  - Rates of gout continue to rise in UK, but GP care has not improved.

PMID- 24435093
TI  - Risk-adjusted mortality rate cumulative sum analysis based on the Japan SCORE
      represents a learning curve in mitral valve reparative surgery.
AB  - PURPOSE: We calculated the cumulative sum analysis of an individual surgical
      learning curve for mitral valve reconstructive surgery to monitor quality
      control. METHODS: Between April 2003 and March 2009, 25 consecutive patients
      underwent mitral valve reconstructive surgery for mitral regurgitation (MR). All
      operations were performed by a single surgeon. We analyzed the operative
      variables, mortality, and major morbidities and calculated the learning curve,
      using descriptive statistics and cumulative sum analysis based on the Japan SCORE
      calculator. RESULTS: In this series, the Japan SCORE calculator predicted a 30
      day operative mortality rate of 3.07 +/- 3.48 % and a 30-day operative mortality
      and morbidity rate of 14.9 +/- 9.58 %s. In reality, there was no operative or in
      hospital death and the major postoperative morbidity rate was 6.0 % (two
      patients). The risk-adjusted cumulative sum analysis revealed that the learning
      curve for mortality and morbidity shifted downward below the lower confident
      interval for all the patients, on completion of mitral valve repair. Coefficient
      analysis revealed a significant negative correlation between the aortic cross
      clamp time and the cardiopulmonary time and case load. There was no correlation
      between the operation time and the case load. CONCLUSIONS: Routine reconstructive
      mitral valve surgery for MR can be performed at the professionally permissive
      level from the beginning, even in low-volume case loads.

PMID- 24435092
TI  - The emerging molecular architecture of schizophrenia, polygenic risk scores and
      the clinical implications for GxE research.
AB  - Schizophrenia is a devastating mental disorder. The level of risk in the general
      population is sustained by the persistence of social, environmental and
      biological factors, as well as their interactions. Socio-environmental risk
      factors for schizophrenia are well established and robust. The same can belatedly
      be said of genetic risk factors for the disorder. Recent progress in
      schizophrenia genetics is primarily fuelled by genome-wide association, which is
      able to leverage substantial proportions of additional explained variance
      previously classified as 'missing'. Here, we provide an outline of the emerging
      genetic landscape of schizophrenia and demonstrate how this knowledge can be
      turned into a simple empirical measure of genetic risk, known as a polygenic risk
      score. We highlight the statistical framework used to assess the clinical
      potential of the new score and finally, draw relevance to and discuss the
      clinical implications for the study of gene-environment interaction. 

PMID- 24435094
TI  - Single-crystalline hyperbranched nanostructure of iron hydroxyl phosphate
      Fe5(PO4)4(OH)3.2H2O for highly selective capture of phosphopeptides.
AB  - Single-crystalline hyperbranched nanostructures of iron hydroxyl phosphate
      Fe5(PO4)4(OH)3.2H2O (giniite) with orthorhombic phase were synthesized through a
      simple route. They have a well-defined dendrite fractal structure with a
      pronounced trunk and highly ordered branches. The toxicity test shows that the
      hyperbranched nanostructures have good biocompatibility and low toxicity level,
      which makes them have application potentials in life science. The study herein
      demonstrated that the obtained hyperbranched giniite nanostructures show highly
      selective capture of phosphopeptides and could be used as a kind of promising
      nanomaterial for the specific capture of phosphopeptides from complex tryptic
      digests with the detection of MALDI-TOF mass spectrometry. 

PMID- 24435097
TI  - Repair of rheumatic mitral stenosis with bicommissural release, anterior leaflet
      augmentation and oversized annuloplasty.
AB  - Rheumatic mitral valve disease often manifests with leaflet fibrosis, commissural
      fusion and early calcific degeneration. The thickening and fibrosis of the
      valvular and subvalvular apparatus has made prosthetic mitral replacement the
      traditional surgical solution. However, favourable valve morphology in some
      patients may permit a durable mitral repair rather than replacement. There is
      growing interest in reparative techniques that durably improve the mitral orifice
      while preserving the subvalvular apparatus. Many of these techniques are
      technically challenging and require complex resections with intricate chordal
      adjustments, which may have limited their global acceptance. In this report, we
      outline a three-step technique that does not require significant resection or
      involve the use of neochords. This offers a potentially simplified approach to
      the repair of rheumatic mitral stenosis. 

PMID- 24435098
TI  - Chordal relocation for repair of anterior mitral leaflet flail: a reproducible
      option.
AB  - Repair of anterior mitral leaflet (AML) flail is considered to be among the more
      technically challenging mitral procedures. While neochord reconstruction is an
      excellent technique, sizing challenges may limit wide reproducibility. Chordal
      relocation of secondary or tertiary AML chords can minimize sizing imprecision in
      open or minimally invasive repair while providing patients with a safe, durable
      and reproducible option. Native chords can be readily released and re-implanted
      from positions in the body of the leaflet to provide primary AML support,
      provided there is preservation of ipsilateral papillary muscle alignment. We
      illustrate the sole use of this reproducible method to repair AML flail. 

PMID- 24435095
TI  - From proliferation to proliferation: monocyte lineage comes full circle.
AB  - Monocytes are mononuclear circulating phagocytes that originate in the bone
      marrow and give rise to macrophages in peripheral tissue. For decades, our
      understanding of monocyte lineage was bound to a stepwise model that favored an
      inverse relationship between cellular proliferation and differentiation.
      Sophisticated molecular and surgical cell tracking tools have transformed our
      thinking about monocyte topo-ontogeny and function. Here, we discuss how recent
      studies focusing on progenitor proliferation and differentiation, monocyte
      mobilization and recruitment, and macrophage differentiation and proliferation
      are reshaping knowledge of monocyte lineage in steady state and disease. 

PMID- 24435096
TI  - Circadian rhythms in leukocyte trafficking.
AB  - A broad range of immunological processes oscillates over the course of a day.
      Recent findings have identified a molecular basis for the circadian clock in the
      regulation of the immune system. These rhythms manifest themselves in oscillatory
      behavior of immune cells and proinflammatory mediators, which causes a time
      dependent sensitivity in the reaction to pathogens. This rhythmicity impacts
      disease manifestations and severity and provides an option for therapy that
      incorporates chronopharmacological considerations. This review will focus on the
      current knowledge and relevance of rhythmic immune cell trafficking. It will
      provide an overview of the molecular clock machinery and its interrelations with
      leukocyte migration and the immune response. 

PMID- 24435099
TI  - A self-propelled biohybrid swimmer at low Reynolds number.
AB  - Many microorganisms, including spermatozoa and forms of bacteria, oscillate or
      twist a hair-like flagella to swim. At this small scale, where locomotion is
      challenged by large viscous drag, organisms must generate time-irreversible
      deformations of their flagella to produce thrust. To date, there is no
      demonstration of a self propelled, synthetic flagellar swimmer operating at low
      Reynolds number. Here we report a microscale, biohybrid swimmer enabled by a
      unique fabrication process and a supporting slender-body hydrodynamics model. The
      swimmer consists of a polydimethylsiloxane filament with a short, rigid head and
      a long, slender tail on which cardiomyocytes are selectively cultured. The
      cardiomyocytes contract and deform the filament to propel the swimmer at 5-10 MUm
      s(-1), consistent with model predictions. We then demonstrate a two-tailed
      swimmer swimming at 81 MUm s(-1). This small-scale, elementary biohybrid swimmer
      can serve as a platform for more complex biological machines.

PMID- 24435100
TI  - [Midterm results following denervation of the ankle].
AB  - BACKGROUND: Complications related to arthrodesis of the ankle or total ankle
      replacement require a critical assessment of the indication. Using denervation of
      the ankle, we have the possibility to delay the above-named surgical treatment
      for a number of years. The aim of this follow-up study was to review the results
      of ankle denervation after several years. METHODS: Within a follow-up
      examination, we were able to evaluate the results of 45 patients an average of
      102 months following ankle denervation. RESULTS: A total of 82.2% of patients
      indicated an improvement of pain for an average of 60.9 months; 71.1% of patients
      reported that the operation was worthwhile. The AOFAS score improved from an
      average 37.9 (range 26-68) preoperatively to 55.6 (range 24-84) at follow-up.
      CONCLUSIONS: Ankle denervation can achieve good ankle pain reduction in the
      treatment of ankle arthrosis. Denervation should be considered a long-term
      treatment concept.

PMID- 24435101
TI  - [Near-infrared spectroscopy for the detection of traumatic intracranial
      hemorrhage: Feasibility study in a German army field hospital in Afghanistan].
AB  - Traumatic brain injury (TBI) is one of the most common causes of death in
      ordinary accidents, natural disasters, or warfare. The gold standard for
      diagnosis of TBI is the CT scan; a delay of diagnostics or medical care is the
      strongest independent predictor of mortality of TBI patients--particularly in the
      case of a surgically treatable intracranial hematoma. The proper classification
      of these patients is of major importance in situations where a CT is not
      accessible. A portable screening device that uses near-infrared spectroscopy
      (NIRS) technology allows a preliminary estimate of an intracranial hematoma. This
      study assessing practicability shows that the use of the device in a military
      medical rescue center (Kunduz, Afghanistan) is easy to learn and can be
      repeatedly used even under emergency room conditions. The technique can be
      applied in penetrating and blunt TBIs in the absence of an immediately available
      CT scan in rural areas, preclinically, under mass casualty conditions (e.g., in
      disaster situations) as well as in humanitarian crises or war zones.
      Nevertheless, further studies to assess the validity of this device are
      necessary.

PMID- 24435102
TI  - [Geriatric complex treatment of proximal femoral fractures? Who profits the
      most?].
AB  - BACKGROUND: Geriatric complex treatment (GCT) is a new type of early
      rehabilitative care. The main goal is to maintain personal autonomy. GCT includes
      21 treatments by physio-, occupational and speech therapists, accompanied by
      specialized nurses. The aim of this study was to investigate how elderly patients
      benefit from the GCT after hip fractures (HF). PATIENTS AND METHODS: In all, 124
      patients [>=70 years; 50 patients underwent GCT, 74 underwent standard
      traumatologic care (STC)] after operative treatment for HF were included.
      Cognitive impairment was diagnosed in 46% of GCT patients and 70% were classified
      as ASA III. In the STC group, 23% were cognitively impaired and 50% were
      classified ASA III. RESULTS: Significantly more patients of the GCT group were
      both cognitively impaired and classified as ASA III. Among the cognitively
      impaired, the STC group reached a median of 20 points on the Barthel index, while
      the GCT group reached 60 points. CONCLUSION: The GCT patients in our study were
      more likely to be dependent on care and have cognitive deficits. Only cognitively
      impaired patients were shown to benefit from GCT. In the remaining patients no
      difference was found, thus, only cognitively impaired patients currently undergo
      GCT at our clinic.

PMID- 24435103
TI  - Decreased maturation of dendritic cells in the central airways of COPD patients
      is associated with VEGF, TGF-beta and vascularity.
AB  - BACKGROUND: Dendritic cells (DCs) have a pivotal role in the onset and regulation
      of innate and adaptive immune responses. Moreover, DCs can interact with
      angiogenic modulators, resulting in modification of their biology and
      participation in angiogenesis. OBJECTIVES: This study was designed to evaluate
      the relationship between the density of DCs, vascularity and expression of
      angiogenic factors [vascular endothelial growth factor (VEGF), transforming
      growth factor (TGF)-beta and basic fibroblast growth factor (bFGF)] in the
      central airways of chronic obstructive pulmonary disease (COPD) patients.
      METHODS: The study included 20 patients with moderate/severe COPD and 8 healthy
      control subjects. Bronchial biopsies were evaluated by immunohistochemistry.
      Specimens were examined for CD83 and CD207 to mark mature and immature DCs,
      respectively, for collagen IV to evaluate vascularity, and for VEGF, TGF-beta and
      bFGF. RESULTS: Compared to controls, COPD patients had a significant reduction of
      CD83+ cells and an increased CD207/CD83 ratio (p < 0.05). Vascularity, VEGF, TGF
      beta and bFGF were also significantly increased in COPD patients as compared to
      controls (p < 0.01). In COPD patients, CD83+ cells were inversely related to VEGF
      and TGF-beta expression (p < 0.05). Moreover, the CD207/CD83 ratio was positively
      related to VEGF, TGF-beta and vascularity (p < 0.05). Finally, CD207+ cells were
      inversely related to FEV1 (p < 0.05). CONCLUSION: Our results show a reduced
      maturation of DCs in COPD that was related to airway vascularity and angiogenic
      factors (VEGF and TGF-beta). Additionally, immature DCs were significantly
      related to disease severity. We propose that the interplay between airway
      vascular changes, on one hand, and DCs maturation on the other, may play a key
      role in the pathogenetic mechanisms of COPD.

PMID- 24435104
TI  - Cross-validation of the recumbent stepper submaximal exercise test to predict
      peak oxygen uptake in older adults.
AB  - BACKGROUND: Submaximal exercise testing can have a greater application in
      clinical settings because peak exercise testing is generally not available. In
      previous work, a prediction equation was developed to estimate peak oxygen
      consumption (Vo2) using a total body recumbent stepper (TBRS) and the Young Men's
      Christian Association (YMCA) protocol in adults who were healthy. OBJECTIVE: The
      purpose of the present study was to cross-validate the TBRS peak Vo2 prediction
      equation in older adults. DESIGN: A cross-sectional study was conducted. METHODS:
      Thirty participants (22 female, 8 male; mean age=66.8 years, SD=5.52; mean
      weight=68.51 kg, SD=13.39) who previously completed a peak exercise test and met
      the inclusion criteria were invited to participate in the cross-validation study.
      Within 5 days of the peak Vo2 test, participants completed the TBRS submaximal
      exercise test. The TBRS submaximal exercise test equation was used to estimate
      peak Vo2. The variables in the equation included age, weight, sex, watts (at the
      end of the submaximal exercise test), and heart rate (at the end of the
      submaximal exercise test). RESULTS: A strong correlation was found between the
      predicted peak Vo2 and the measured peak Vo2. The difference between the values
      was 0.9 mL.kg(-1).min(-1), which was not statistically different. The standard
      error of the estimate was 4.2 mL.kg(-1).min(-1). LIMITATIONS: The sample included
      individuals who volunteered to perform a peak exercise test, which may have
      biased the results toward those willing to exercise to fatigue. CONCLUSION: The
      data suggest the TBRS submaximal exercise test and prediction equation can be
      used to predict peak Vo2 in older adults. This finding is important for health
      care professionals wanting to provide information to their patients or clients
      regarding their fitness level.

PMID- 24435105
TI  - Effectiveness of mat Pilates or equipment-based Pilates exercises in patients
      with chronic nonspecific low back pain: a randomized controlled trial.
AB  - BACKGROUND: The Pilates method has been widely used to treat patients with
      chronic low back pain. Pilates exercises can be performed in 2 ways: by using
      specific equipment or without it (also known as mat Pilates). There are no
      studies, however, that have compared the effectiveness of mat Pilates with that
      of equipment-based Pilates. OBJECTIVE: The aim of this study was to compare the
      effectiveness of mat Pilates and equipment-based Pilates in patients with chronic
      nonspecific low back pain. DESIGN: A 2-arm randomized controlled trial with a
      blinded assessor was conducted. SETTING: The study was conducted at a private
      physical therapy clinic in Brazil. PATIENTS: Eighty-six patients with chronic
      nonspecific low back pain participated. INTERVENTION: The patients were randomly
      allocated to 1 of 2 groups: a mat Pilates group (n=43) and an equipment-based
      Pilates group (n=43). The participants in both groups attended 12 Pilates
      sessions over a period of 6 weeks. MEASUREMENTS: The primary outcomes were pain
      intensity and disability. The secondary outcomes were global perceived effect,
      patient's specific disability, and kinesiophobia. A blinded assessor evaluated
      the outcomes at baseline and 6 weeks and 6 months after randomization. RESULTS:
      After 6 months, there was a statistically significant difference for disability
      (mean difference=3.0 points, 95% confidence interval [CI]=0.6 to 5.4), specific
      disability (mean difference=-1.1 points, 95% CI=-2.0 to -0.1), and kinesiophobia
      (mean difference=4.9 points, 95% CI=1.6 to 8.2) in favor of equipment-based
      Pilates. No differences were found for the remaining outcomes. CONCLUSIONS:
      Equipment-based Pilates was superior to mat Pilates in the 6-month follow-up for
      the outcomes of disability and kinesiophobia. These benefits were not observed
      for pain intensity and global perceived effect in patients with chronic
      nonspecific low back pain.

PMID- 24435106
TI  - Design of a TiO2 nanosheet/nanoparticle gradient film photoanode and its improved
      performance for dye-sensitized solar cells.
AB  - A TiO2 film photoanode with gradient structure in nanosheet/nanoparticle
      concentration on the fluorine-doped tin oxide glass from substrate to surface was
      prepared by a screen printing method. The as-prepared dye-sensitized solar cell
      (DSSC) based on the gradient film electrode exhibited an enhanced photoelectric
      conversion efficiency of 6.48%, exceeding that of a pure nanoparticle-based DSSC
      with the same film thickness by a factor of 2.6. The enhanced photovoltaic
      performance of the gradient film-based DSSC was attributed to the superior light
      scattering ability of TiO2 nanosheets within the gradient structure, which was
      beneficial to light harvesting. Furthermore, the TiO2 nanosheets with exposed
      {001} facets facilitated the electron transport from dye molecules to the
      conduction band of TiO2 and further to the conductive glass. Meanwhile, the high
      specific surface area of TiO2 nanosheets helped the adsorption of dye molecules,
      and the TiO2 nanoparticle underlayer ensured good electronic contact between the
      TiO2 film and the fluorine-doped tin oxide glass substrate. The electrochemical
      impedance spectroscopy measurements further confirmed the electron transport
      differences between DSSCs based on nanosheet/nanoparticle gradient film
      electrodes and DSSCs based on nanosheet/nanoparticle homogeneous mixtures, pure
      TiO2 nanoparticles and pure TiO2 nanosheets with the same film thickness. 

PMID- 24435107
TI  - Predictive value of thrombus attenuation on thin-slice non-contrast CT for
      persistent occlusion after intravenous thrombolysis.
AB  - BACKGROUND: In stroke erythrocyte-rich thrombi are more sensitive to intravenous
      thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have
      higher density on non-contrast CT (NCCT). We investigated the relationship
      between thrombus density and recanalization and whether persistent occlusions can
      be predicted by Hounsfield unit (HU) measurements. METHODS: In 88 IV-rtPA-treated
      patients with intracranial ICA or MCA occluding thrombus and follow-up imaging,
      thrombus and contralateral vessel attenuation measurements were performed on thin
      slice NCCT. Mean absolute and relative HU were compared between patients with
      persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade
      0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted
      for stroke subtype, clot burden score, occlusion site and time to thrombolysis)
      odds ratios for persistent occlusion were calculated. Additional prognostic value
      for persistent occlusion was estimated by adding HU measurements to the area
      under the curve (AUC) of known determinants and calculating optimal cut-off
      values. RESULTS: Patients with persistent occlusion (n = 19) had significant
      lower mean HU (absolute 52.2 +/- 9.5, relative 1.29 +/- 0.20) compared to
      recanalization (absolute 63.1 +/- 10.7, relative 1.54 +/- 0.23, both p < 0.0001).
      Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6
      6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease
      and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per
      0.20 relative HU decrease. Attenuation measurements significantly increased the
      AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative
      HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal
      predictive values for persistent occlusion. CONCLUSIONS: Thrombus density is
      related to recanalization rate. Lower absolute and relative HU are independently
      related to persistent occlusion and HU measurements significantly increase
      discriminative performances of known recanalization determinants.

PMID- 24435108
TI  - Temperature-dependent photocatalytic hydrogen evolution activity from water on a
      dye-sensitized layered titanate.
AB  - Visible light-induced hydrogen evolution activity from water on a ruthenium
      complex-sensitized layered titanate was modified when the reaction was conducted
      at higher temperature. 

PMID- 24435111
TI  - An actress (portrait of Suzanne Santje): Thomas Eakins.

PMID- 24435112
TI  - Nasal valve collapse treatment.

PMID- 24435113
TI  - Patient privacy, clinical photographs, and publication.

PMID- 24435114
TI  - Glued diced cartilage graft for augmentation rhinoplasty.

PMID- 24435115
TI  - Glued diced cartilage graft for augmentation rhinoplasty.

PMID- 24435117
TI  - Post-sternotomy mediastinitis after cardiac surgery.

PMID- 24435118
TI  - Topical negative pressure improves autograft take by altering nutrient diffusion:
      A hypothesis.
AB  - The one-step surgical procedure for dermal substitutes combined with topical
      negative pressure (TNP) has proven effective for treating deep skin defects with
      improved graft take. The primary mechanism by which TNP improves autograft take
      is unknown. Some studies suggest that TNP promotes the rapid angiogenesis of
      dermal substitutes, improving graft take. However, at the early stage of one-step
      transplantation, the vascular system has not formed and imbibition is the main
      mode of nutrient supply. TNP can shorten the diffusion distance from the wound
      bed to the graft, leading to the timely renewal of the wound exudate via suction,
      removing any surplus exudate, and reducing tissue edema. In addition, TNP can
      regulate the local blood flow and inhibit bacterial colonization. Therefore, we
      hypothesized that TNP establishes a rapid balance between the nutrient supply to
      the wound bed and nutritional requirement of the graft via these pathways in the
      relatively closed, moist environment, improving autograft take. However, this
      balance could be affected by any negative pressure, intermittent or continuous.
      It is necessary to test this hypothesis in laboratory and clinical studies of the
      mode of nutrient supply in the imbibition phase and the change in exudate
      content. 

PMID- 24435120
TI  - Experimentally induced binding of phytochrome to mitochondrial and microsomal
      fractions in etiolated pea shoots.
AB  - A brief irradiation with red light of pea (Pisum sativum L.) shoot segments kept
      at 0 degrees  resulted in very rapid binding of both Pr and Pfr to mitochondrial
      and microsomal fractions. The effect was not far-red reversible. The amount of
      phytochrome bound to the mitochondrial fraction was proportional to the
      percentage of Pfr of the fraction, and the ratio of Pr and Pfr in the bound form
      was the same as that in 12,000 x g supernatant. After a brief exposure of the
      segments to red light at 0 degrees  and a subsequent dark incubation at 30
      degrees  in Tris-HCL buffer containing dithiothreitol or EDTA, which bot inhibit
      Pfr decay, the contents of phytochrome in the mitochondrial and microsomal
      fractions were significantly enhanced with time. The red-light effect was
      reversed by far-red light. The increase of the phytochrome content in the
      particulate fractions continued for at least 2 h, reaching a ca. 3 times higher
      level in terms of Delta (DeltaA) per mg protein. 

PMID- 24435121
TI  - The role of the root cap in the response of the primary roots of Zea mays L.
      seedlings to white light and to gravity.
AB  - Investigations into the relationship between the light-induced inhibition of root
      elongation and the response of Zea mays primary roots to gravity have revealed a
      close similarity between growth-inhibiting factor(s) produced in response to both
      stimuli. Evidence is presented that the inhibiting factor(s) produced in the root
      cap on exposure to white light can be used by the root to produce curvature in
      response to gravitational stimulation in darkness, i.e. under conditions in which
      dark exposed roots do not normally respond to gravity.The implications of these
      findings on the way in which roots respond to geotropic stimulation are
      discussed. 

PMID- 24435119
TI  - Surface antigen profiles of leukocytes and melanoma cells in lymph node
      metastases are associated with survival in AJCC stage III melanoma patients.
AB  - There is an urgent need to identify more accurate prognostic biomarkers in
      melanoma patients, particularly in those with metastatic disease. This study
      aimed to identify melanoma and leukocyte surface antigens predictive of survival
      in a prospective series of AJCC stage IIIb/c melanoma patients (n = 29). Live
      cell suspensions were prepared from melanoma metastases within lymph nodes (LN).
      The suspensions were immuno-magnetically separated into CD45(+) (leukocyte) and
      CD45(-) (non-hematopoietic, enriched melanoma cell) fractions. Surface antigens
      on CD45(-) and CD45(+) cell populations were profiled using DotScanTM microarrays
      (Medsaic Pty. Ltd.) and showed differential abundance levels for 52 and 78
      antigens respectively. Associations of the surface profiles with
      clinicopathologic and outcome data (median follow-up 35.4 months post LN
      resection) were sought using univariate (log-rank test) and multivariate (Wald's
      test; modelled with patient's age, gender and AJCC staging at LN recurrence)
      survival models. CD9 (p = 0.036), CD39 (p = 0.004) and CD55 (p = 0.005) on
      CD45(+) leukocytes were independently associated with distant metastasis-free
      survival using multivariate analysis. Leukocytes with high CD39 levels were also
      significantly associated with increased overall survival (OS) in multivariate
      analysis (p = 0.016). LNs containing leukocytes expressing CD11b (p = 0.025),
      CD49d (p = 0.043) and CD79b (p = 0.044) were associated with reduced OS on
      univariate analysis. For enriched melanoma cells (CD45(-) cell populations), 11
      surface antigens were significantly correlated with the disease-free interval
      (DFI) between diagnosis of culprit primary melanoma and LN metastasis resection.
      Nine antigens on CD45(+) leukocytes also correlated with DFI. Following
      validation in independent datasets, surface markers identified here should enable
      more accurate determination of prognosis in stage III melanoma patients and
      provide better risk stratification of patients entering clinical trials.

PMID- 24435122
TI  - Particle-bound phytochrome: Association with a ribonucleoprotein fraction from
      Cucurbita pepo L.
AB  - In the absence of ethylenediaminetetraacetic acid (EDTA) and added Mg(2+), the
      phytochrome, RNA, protein, cytochrome c oxidase and NADPH-cytochrome c reductase
      in 20000 x g pellets from hypocotyl hooks of red-irradiated Cucurbita seedlings
      are more or less coincident in a single, broad band on linear sucrose gradients.
      The inclusion of 3 mM EDTA in the extraction, resuspension and gradient media has
      three major effects: (a) The phytochrome profile splits into two main bands; (b)
      the main RNA population shifts to a sharp peak which co-sediments with the
      "lighter" phytochrome band at 31S; (c) the main NADPH-cytochrome c reductase peak
      shifts to a lower density. This indicates that the EDTA dissociates a rough
      endoplasmic-reticulum fraction into separate membrane and ribonucleoprotein (RNP)
      components, and that part of the phytochrome is associated with the latter. The
      31S RNP fraction is 35-40% RNA, has a 260/235 nm absorption ratio of 1.36 and the
      RNA dissociates into small fragments in sodium dodecyl sulfate. More than 90% of
      the phytochrome and RNA in the isolated 31S fraction becomes pelletable upon the
      addition of 10 mM Mg(2+). Higher Mg(2+) levels release the phytochrome and some
      of the other protein present from the RNA which remains pelletable. The data
      indicate that the 31S RNP fraction may be degraded ribosomal material with
      extraneously bound protein, including phytochrome. Several aspects of phytochrome
      binding to particulate fractions which have been reported in the literature are
      consistent with an interaction of Pfr with ribosomal material-degraded or
      otherwise. 

PMID- 24435123
TI  - Particle-bound phytochrome: The nature of the interaction between pigment and
      particulate fractions.
AB  - Particle-bound phytochrome from hypocotyl hooks of Cucurbita pepo L. seedlings is
      associated with either a "heavy" membrane fraction or a 31S ribonucleoprotein
      (RNP) component on sucrose gradients. Those amounts of phytochrome and RNP which
      co-pellet in response to added Mg(2+) are primarily localised in the 31S
      fraction. The phytochrome-RNP association itself, however, is not dependent on
      the added cation. This indicates that Mg(2+)-enhanced phytochrome pelletability
      results indirectly from aggregation of the RNP material. Phytochrome binds
      readily to this RNP fraction whether converted to the Pfr form in vivo or in
      vitro. Once bound, in either case, however, the pigment is not released by
      reconversion to Pr in vitro. Treatment of pellets with Triton X-100 causes most
      of the phytochrome to become sedimentable through 50% (w/w) sucrose, possibly
      indicative of pigment denaturation. Increasing the pH, in contrast, causes that
      phytochrome formerly located in the "heavy" membrane fraction to become
      associated with the 31S RNP component. High KCl concentrations dissociate the
      pigment from both "heavy" and 31S fractions, indicating the ionic nature of the
      interaction in both cases. These data can be accounted for by the electrostatic
      adsorption of phytochrome to ribosomal material, either ER-associated in the
      "heavy" fraction or "free" in the 31S fraction.Maize (Zea mays L.) exhibits a
      different pattern. Although Mg(2+) enhances the initial pelletability of both
      phytochrome and RNA the two components subsequently separate on Mg(2+)-free
      gradients.The data indicate that current interpretations of particle-bound
      phytochrome in terms of pigment-membrane interactions may need to be re-examined.

PMID- 24435124
TI  - The occurrence and ultrastructure of chloroplasts in the phloem parenchyma of
      leaves of C4 dicotyledons.
AB  - Chloroplasts were found to be common within the phloem parenchyma of leaves of
      dicotyledons, although they were not observable, at the light microscope level,
      in the vascular cells of any grasses examined. The phloem-cell chloroplasts of
      Boerhaavia paniculata L. and Portulaca oleracea L. (both C4 plants) were
      structurally similar to each other, even though the chloroplasts of their
      surrounding bundle sheaths were of different types. They were also similar to the
      phloem-cell chloroplasts of Phaseolus vulgaris L. (C3 plant). Although
      consistently small, all vascular plastids appeared normal. The extent of their
      functionality is unknown. 

PMID- 24435125
TI  - [Regulation of peroxidase patterns during shoot differentiation in callus
      cultures of Nicotiana tabacum L].
AB  - Peroxidase activity and isoenzyme pattern were studied during dedifferentiation
      of tobacco stem-sections leading to callus formation and during redifferentiation
      of tobacco callus leading to formation of shoots. These processes are both
      accompanied by an increase in total peroxidase activity and by characteristic
      changes in isoenzyme pattern. The isoenzyme pattern of tobacco callus differs
      from that of tobacco stem-tissue. The plantlets differentiated from the callus
      show the same pattern as seedlings do.During the differentiation process, before
      any buds are visible, the callus shows a peroxidase pattern that is determined by
      a reduction of fast-migrating anodic isoenzymes and by an increase of activity in
      all the other peroxidase isoenzymes. The formation of this pattern is independent
      of the growth regulators responsible for the differentiation: only the kind of
      differentiation itself determines the pattern.By artificial inhibition of callus
      growth it is possible to induce an isoenzyme pattern very similar to that of
      differentiation; the fast-migrating anodic enzymes are reduced in activity but
      the others are not increased as they are during differentiation. Therefore the
      question arises whether there are two independent processes taking place in
      differentiating callus. The one process, inhibition of growth in the cells that
      do not differentiate, is accompanied by a reduction of fast-migrating anodic
      isoenzymes. The other process, formation of meristemoids in the callus, is
      accompanied by a sharp rise in peroxidase activity of the other anodic and
      cathodic isoenzymes. 

PMID- 24435126
TI  - Parental factors in dominance of lateral buds on rhizomes of Agropyron repens
      (L.) beauv.
AB  - A mixture of 1-naphthylacetic acid and 6-benzylaminopurine was found to be an
      effective substitute for the rhizome apex of attached rhizomes, when the plants
      were not at anthesis. The same mixture was not effective, however, when the
      plants were at anthesis. The same growth-regulators applied to the apical end of
      detached multi-node rhizome fragments did not maintain correlative inhibition
      unless growth-regulators were simultaneously applied to the basal end. Various
      interactions between apical and basal applications are discussed with regard to
      their role as a parental factor in apical dominance. 

PMID- 24435127
TI  - Cellulose microfibril deposition at the plasmalemma surface of regenerating
      tobacco mesophyll protoplasts: A deep-etch study.
AB  - The reappearance of cellulose microfibrils at the naked surface of protoplasts
      enzymatically isolated from tobacco (Nicotiana tabacum L. var. Xanthi) mesophyll
      tissue has been closely studied using the techniques of thin-sectoining and the
      deep-etch modification of the freeze fracture procedure.A 16 h lag period was
      recorded between the time of isolation and the sudden appearance of considerable
      lengths of cellulose microfibril at the outer protoplast surface. The
      microfibrils were not associated with any structured particles or apparently
      differentiated regions of the plasmalemma. Terminal regions of the microfibrils
      appeared to have tapering ends, or else be sinking into the membrane substance.
      There was no evidence to suggest transport of intact microfibrils in vesicles
      through the cytoplasm to the plasmalemma.The reported observations have been
      discussed with respect to the various working hypotheses which have been proposed
      for the 'in vivo' construction of cellulose microfibrils. 

PMID- 24435128
TI  - [The effect of barbital on golgi bodies in meristematic root tip cells of allium
      sativum L].
AB  - In meristematic root tip cells of Allium sativum L. treatment with barbital under
      appropriate conditions results in a marked increase in the number of Golgi
      cisternae and a progressive decrease in the rate of release of Golgi vesicles.
      Connections between endoplasmic reticulum and Golgi bodies, indicated by OsO4
      staining, which presumably involve transitional vesicles are not disrupted. The
      significance of multivesicular bodies containing small Golgian vesicles is
      discussed. The results show that formation of Golgi cisternae from endoplasmic
      reticulum is still possible but that their maturation with production of
      elaborated substances is progressively inhibited. 

PMID- 24435129
TI  - The abscisic acid content of dormant birch buds.
AB  - Abscisic acid (ABA) has been identified in the buds and xylem sap of Betula
      verrucosa (Ehrh.). Buds also contain esterified ABA. In the course of the winter
      the proportion of esterified ABA in the buds undergoes a progressive increase
      which may be associated with emergence from dormancy. 

PMID- 24435130
TI  - Two types of carbon fixation in tropical orchids.
AB  - The isotopic composition of the carbon (delta(13)C values) of leaf tissue from 10
      species and hybrids of orchids grown in Singapore fell into two groups, one
      having a mean value of-15.40/00, the other-26.60/00. The least negative of these
      values was associated with thick-leaved plants (0.2-0.4 mm). This is consistent
      with the view that some orchids are CAM plants and others possess a C3 type of
      carbon fixation. 

PMID- 24435131
TI  - Organogenesis from Callus Culture of Hordeum vulgare.
AB  - Rapidly proliferating callus cultures from the apical meristem of Hordeum vulgare
      L., cultivars "Himalaya" and "Mari", were established on a defined medium
      supplemented with auxin and cytokinin. A frequency of organ differentiation of
      ca. 85% was obtained by transfer to the same medium but without any growth
      regulators. All regenerated plants had the diploid chromosome number of 14 (2n). 

PMID- 24435132
TI  - Phytochrome medicated changes in extractable gibberellin activity in a cell-free
      system from etiolated wheat leaves.
AB  - Irradiation with red light causes a phytochrome dependent increase in the
      extractable amount of acidic gibberellin-like activity in plastid preparations
      from etiolated leaves of Triticum aestivum L. 

PMID- 24435133
TI  - Water amount dependence on morphologies and properties of ZnO nanostructures in
      double-solvent system.
AB  - ZnO materials with a range of different morphologies have been successfully
      synthesized via a simple double-solvothermal method in the presence of glycine.
      The morphologies of the products can be controlled from superstructures to
      microrods by adjusting the amount of water in the EtOH/H2O system.
      Photoluminescence (PL) studies reveal that the more amount of water was used, the
      stronger PL relative intensity of the green emission is, but the weaker
      ultraviolet emission. This might be attributed to the more defects of the
      products when the more water was used. The catalytic studies show that all the
      samples have good abilities to decrease decomposition temperature around 300
      degrees C and the decomposition temperature lowers with the increase of the
      relative intensity of ZnO green emission. 

PMID- 24435135
TI  - Source identification of particulate matter in a semi-urban area of Malaysia
      using multivariate techniques.
AB  - This study aims to determine the composition and sources of particulate matter
      with an aerodynamic diameter of 10 MUm or less (PM10) in a semi-urban area. PM10
      samples were collected using a high volume sampler. Heavy metals (Fe, Zn, Pb, Mn,
      Cu, Cd and Ni) and cations (Na(+), K(+), Ca(2+) and Mg(2+)) were detected using
      inductively coupled plasma mass spectrometry, while anions (SO4 (2-), NO3 (-),
      Cl(-) and F(-)) were analysed using Ion Chromatography. Principle component
      analysis and multiple linear regressions were used to identify the source
      apportionment of PM10. Results showed the average concentration of PM10 was 29.5
      +/- 5.1 MUg/m(3). The heavy metals found were dominated by Fe, followed by Zn,
      Pb, Cu, Mn, Cd and Ni. Na(+) was the dominant cation, followed by Ca(2+), K(+)
      and Mg(2+), whereas SO4 (2-) was the dominant anion, followed by NO3 (-), Cl(-)
      and F(-). The main sources of PM10 were the Earth's crust/road dust, followed by
      vehicle emissions, industrial emissions/road activity, and construction/biomass
      burning.

PMID- 24435136
TI  - Ionic composition of rainwater at selected sites of Kuantan, Pahang, Malaysia: a
      preliminary study.
AB  - A short-term investigation on the chemical composition of rainwater was carried
      out at five selected sampling stations in Kuantan district, Pahang, Malaysia.
      Sampling of rainwater was conducted by event basis between September and November
      2011. Rainwater samples were collected using polyethylene containers and the
      parameters measured were cations (sodium, potassium, ammonium, calcium and
      magnesium) and anions (chlorides, nitrates and sulphates). The average pH value
      for rainwater samples was 6.0 +/- 0.57 in which most of the sampling sites
      exhibited pH values >5.6. Calcium and sulphate were the most abundant cation and
      anion, respectively, whilst the concentrations of other major ions varied
      according to sampling location.

PMID- 24435134
TI  - Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in
      apolipoprotein-E4 targeted replacement mice.
AB  - Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease.
      Although intranasal insulin can improve cognition, this has little effect in
      ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined
      brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At
      32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt
      phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to
      fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to
      lower brain glucose content and have no effect on plasma glucose level. However,
      at 72 weeks of age, these early changes were accompanied by reduction in IRS2
      expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK
      (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain
      glucose was significantly associated with higher brain insulin in the aged
      huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling
      and glucose level leading to higher insulin content. 

PMID- 24435138
TI  - Surgical resection can be successful in a large fraction of patients with drug
      resistant epilepsy associated with multiple cerebral cavernous malformations.
AB  - BACKGROUND: Multiple cerebral cavernous malformations (mCCMs) are known as
      potentially epileptogenic lesions. Treatment might be multimodal. Management of
      patients with mCCMs and epilepsy is challenging. OBJECTIVE: To evaluate (1)
      algorhythmic therapeutic sequences in patients with epilepsy associated to mCCMs,
      (2) whether there are predictive parameters to anticipate the development of drug
      resistant epilepsy, and (3) seizure after epilepsy surgery compared to
      conservatively-treated drug-resistant patients. METHODS: All inpatients and
      outpatients with epilepsy associated to mCCMs from 1990 to 2010 and follow-up >12
      months available were retrospectively analyzed. RESULTS: Twenty-three patients
      matched inclusion criteria. Epilepsy became drug-resistant in 18/23 (78%)
      patients. No predictors were found for development of drug-resistant epilepsy.
      Median follow-up for both groups was 7.8 years. Nine patients did not qualify for
      surgical therapy and were treated conservatively. One patient of this cohort
      (11%) was seizure-free (International League Against Epilepsy [ILAE] class 1).
      Surgical treatment was performed in 9 patients; 7/9 (78%) of these patients were
      seizure-free (ILAE class 1) after epilepsy surgery for at least 12 months
      compared with 1/9 patients in the non-operated group. In 7/9 cases (78%) the
      largest CCM was resected. In 8/9 (89%) not all CCMs were resected. CONCLUSION:
      After initial diagnosis of epilepsy associated to mCCMs, a primary conservative
      approach is reasonable. Surgical treatment can be successful in a large fraction
      of cases with drug-resistant epilepsy where an epileptogenic lesion is
      identified. Cases where surgery is not undertaken are likely to remain
      intractable.

PMID- 24435139
TI  - The epidemiology of admissions of nontraumatic subarachnoid hemorrhage in the
      United States.

PMID- 24435140
TI  - Response to journal club: The epidemiology of admissions of nontraumatic
      subarachnoid hemorrhage in the United States.

PMID- 24435142
TI  - Genetic predisposition to lumbar disc degeneration.

PMID- 24435143
TI  - A randomized clinical trial and meta-analysis of early surgery vs. initial
      conservative treatment in patients with spontaneous lobar intracerebral
      hemorrhage.

PMID- 24435144
TI  - Detecting brain tumor with Raman scattering microscopy.

PMID- 24435145
TI  - Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in
      vivo.

PMID- 24435146
TI  - Scar in the injured spinal cord: the news is not all bad.

PMID- 24435147
TI  - Sleep tight: a purpose for sleep.

PMID- 24435148
TI  - Deep brain stimulation for locomotor recovery following spinal cord injury.

PMID- 24435149
TI  - Traumatic brain injury at your fingertips!

PMID- 24435150
TI  - Intrinsic cortical signal gain: optogenetic silencing reveals active role of
      cortical amplification during sensory input.

PMID- 24435151
TI  - VIGAS and beyond: the impact of HCMV-infection and its treatment in glioblastoma.

PMID- 24435154
TI  - Electronic transport and device prospects of monolayer molybdenum disulphide
      grown by chemical vapour deposition.
AB  - Layered transition metal dichalcogenides display a wide range of attractive
      physical and chemical properties and are potentially important for various device
      applications. Here we report the electronic transport and device properties of
      monolayer molybdenum disulphide grown by chemical vapour deposition. We show that
      these devices have the potential to suppress short channel effects and have high
      critical breakdown electric field. However, our study reveals that the electronic
      properties of these devices are at present severely limited by the presence of a
      significant amount of band tail trapping states. Through capacitance and ac
      conductance measurements, we systematically quantify the density-of-states and
      response time of these states. Because of the large amount of trapped charges,
      the measured effective mobility also leads to a large underestimation of the true
      band mobility and the potential of the material. Continual engineering efforts on
      improving the sample quality are needed for its potential applications. 

PMID- 24435156
TI  - [Cancer of unknown primary. Epidemiology and pathogenesis].
AB  - DEFINITION: The term cancer of unknown primary (CUP) describes by definition
      epithelial malignancies for which no primary tumor can be found after primary
      diagnostics have been performed. EPIDEMIOLOGY: The CUP syndrome constitutes 2-3%
      of all fatal cases of malignancies in both men and women. The proportion of women
      has increased in parallel to the increase of tobacco consumption in women.
      PATHOGENESIS: The most frequent origin appears to lie in the lungs or upper
      abdominal organs, while notable differences can be found between older autopsy
      findings and recent gene expression data with respect to identified primary
      tumors or tissue assignation. The fact that a primary tumor cannot be identified
      is probably based on various reasons: a complete regression of a primary tumor in
      isolated cases seems to be just as plausible as the misclassification of a
      primary tumor as a metastasis. CONCLUSION: In combination with the fact that a
      primary tumor cannot be identified by autopsy in more than 20 % of cases, the
      important conclusion can be drawn that curative approaches seem appropriate for
      localized CUP cases.

PMID- 24435155
TI  - [Lobular neoplasms and invasive lobular breast cancer].
AB  - The term lobular neoplasia (LN) comprises both atypical lobular hyperplasia
      (ALH), and lobular carcinoma in situ (LCIS) and thus a spectrum of
      morphologically heterogeneous but clinically and biologically related lesions. LN
      is regarded as a nonobligatory precursor lesion of invasive breast cancer and at
      the same time as an indicator lesion for ipsilateral and contralateral breast
      cancer risk of the patient. Rare pleomorphic or florid variants of LCIS must be
      differentiated from classical LCIS. The classical type of invasive lobular
      carcinoma (ILC) can be distinguished from the non-special type of invasive breast
      cancer (NST) by E-cadherin inactivation, loss of E-cadherin related cell adhesion
      and the subsequent discohesive growth pattern. Variant forms of ILC may show
      different molecular features, and solid and pleomorphic differentiation patterns
      in cases of high grade variants. Important parameters for the prognostic
      assessment of ILC are tumor grading and the recognition of morphological
      variants. 

PMID- 24435157
TI  - [Structured diagnostics and therapy of the CUP syndrome].
AB  - BACKGROUND: In the majority of cases, patients with cancer of unknown primary
      (CUP) have a poor prognosis with no prospect of being cured. Hence, a reasonable
      focus of diagnostics on its essential targets seems appropriate. PATIENTS:
      Particularly important is the identification of all patients who can be assigned
      to subgroups with a favorable prognosis and who might benefit from a specific
      therapy. For all other patients, platinum-based combination therapy is the
      standard cytostatic therapy. THERAPY: In addition to platinum derivatives,
      taxanes, gemcitabine and irinotecan can also be used. Promising innovative
      approaches include targeted therapies, in particular bevacizumab and erlotinib,
      and identification of the tissue origin with micro-RNA or gene expression
      analyses which can help identify the most suitable organ-specific therapy for
      individual patients. PERSPECTIVES: It would be desirable if the group of patients
      treated with unspecific therapy could be reduced by improved diagnostics so that
      these patients could be treated with organ-specific therapy or with molecularly
      targeted approaches. Micro-RNA and gene expression analyses appear to be
      interesting for this purpose. Another complementary approach is to improve the
      treatment results of patients receiving an unspecific standard combination
      therapy by additional administration of new targeted substances.

PMID- 24435158
TI  - [Imaging of the elbow joint with focused MRI. Part 1: examination techniques and
      sequences for bone and ligaments].
AB  - Imaging of the elbow joint places high demands on the quality of imaging due to
      the challenging anatomy and the sometimes subtle findings. For the diagnosis of
      periarticular soft tissues, ligamentous structures and in individual cases for
      fracture and tumor diagnosis, magnetic resonance imaging (MRI) is mostly
      groundbreaking and allows a reliable diagnosis in most cases. This review article
      discusses the complex imaging anatomy and anatomical variants of this joint and
      the most common osseous and ligamentous injuries of the elbow joint are
      presented. The typical MRI findings and indications are illustrated and discussed
      and possible pitfalls are pointed out. The various examination techniques and MRI
      sequences are also addressed.

PMID- 24435160
TI  - Improving O2 production of WO3 photoanodes with IrO2 in acidic aqueous
      electrolyte.
AB  - WO3 is a promising candidate for a photoanode material in an acidic electrolyte,
      in which it is more stable than most metal oxides, but kinetic limitations
      combined with the large driving force available in the WO3 valence band for water
      oxidation make competing reactions such as the oxidation of the acid counterion a
      more favorable reaction. The incorporation of an oxygen evolving catalyst (OEC)
      on the WO3 surface can improve the kinetics for water oxidation and increase the
      branching ratio for O2 production. Ir-based OECs were attached to WO3 photoanodes
      by a variety of methods including sintering from metal salts, sputtering, drop
      casting of particles, and electrodeposition to analyze how attachment strategies
      can affect photoelectrochemical oxygen production at WO3 photoanodes in 1 M
      H2SO4. High surface coverage of catalyst on the semiconductor was necessary to
      ensure that most minority-carrier holes contributed to water oxidation through an
      active catalyst site rather than a side-reaction through the WO3/electrolyte
      interface. Sputtering of IrO2 layers on WO3 did not detrimentally affect the
      energy-conversion behavior of the photoanode and improved the O2 yield at 1.2 V
      vs. RHE from ~0% for bare WO3 to 50-70% for a thin, optically transparent
      catalyst layer to nearly 100% for thick, opaque catalyst layers. Measurements
      with a fast one-electron redox couple indicated ohmic behavior at the IrO2/WO3
      junction, which provided a shunt pathway for electrocatalytic IrO2 behavior with
      the WO3 photoanode under reverse bias. Although other OECs were tested, only IrO2
      displayed extended stability under the anodic operating conditions in acid as
      determined by XPS.

PMID- 24435159
TI  - Cisplatin dose adjustment in patients with renal impairment, which
      recommendations should we follow?
AB  - BACKGROUND: Nephrotoxicity is the dose-limiting side effect of cisplatin
      justifying the assessment of renal function for dose adjustment. OBJECTIVE: To
      determine whether appropriate dose adjustment is made in patients with renal
      impairment using the Cockcroft-Gault (CG) or the abbreviated Modification of Diet
      in Renal Disease (aMDRD) formulas to estimate the glomerular filtration rate
      (GFR). SETTING: The study was conducted in a 1,000-bed university hospital.
      METHOD: Two years of cisplatin prescriptions were retrospectively compared to the
      4 and 3 ranges estimated glomerular filtration rate (eGFR)-stratified dosing
      recommendations (4RR and 3RR respectively). MAIN OUTCOME MEASURE: Cisplatin dose
      in mg/m(2) based on kidney function and according to the dosing recommendations.
      RESULTS: Among 1,364 cycles of cisplatin, 156 (11.4 %) were prescribed for 70
      patients with eGFR < 60 mL/min and a median age of 67.4 years. For 57 (36 %) of
      these cycles, doses were not reduced. When reduced, prescribed doses were not
      different than recommended doses according to 4RR using CG (% of protocol, 63 +/-
      12 vs. 64 +/- 17) while it was significantly lower using aMDRD (% of protocol, 66
      +/- 12 vs. 81 +/- 22, p < 0.01) and significantly higher according to 3RR using
      both CG and aMDRD (% of protocol, 63 +/- 12 vs. 50 +/- 3 and 66 +/- 12 vs. 50.7
      +/- 4.0 respectively, p < 0.01). Prescription of at least one appropriate dose
      according to 4RR and using aMDRD was associated with a statistically significant
      higher median total cumulative dose (% of protocol, 89.9 vs. 75.1 % respectively,
      p < 0.01) without higher decrease of eGFR over time. CONCLUSION: Cisplatin dose
      adjustment in patients with renal impairment must be improved. Estimating GFR
      with the aMDRD formula and adding an intermediary level of dose reduction for
      patients with eGFR from 50 to 59.9 mL/min may result in a higher cumulative dose
      of cisplatin without higher renal toxicity, which may significantly impact on the
      effectiveness of the chemotherapy. A prospective evaluation remains needed to
      assess the benefit/risk ratio of this dose adaptation schedule, taking into
      account the variability of the GFR estimates.

PMID- 24435161
TI  - Phosphorylation of alfalfa mosaic virus movement protein in vivo.
AB  - The 32-kDa movement protein, P3, of alfalfa mosaic virus (AMV) is essential for
      cell-to-cell spread of the virus in plants. P3 shares many properties with other
      virus movement proteins (MPs); however, it is not known if P3 is
      posttranslationally modified by phosphorylation, which is important for the
      function of other MPs. When expressed in Nicotiana tabacum, P3 accumulated
      primarily in the cell walls of older leaves or in the cytosol of younger leaves.
      When expressed in Pischia pastoris, P3 accumulated primarily in a soluble form.
      Metabolic labeling indicated that a portion of P3 was phosphorylated in both
      tobacco and yeast, suggesting that phosphorylation regulates the function of this
      protein as it does for other virus MPs. 

PMID- 24435162
TI  - Co-delivery of LIGHT expression plasmid enhances humoral and cellular immune
      responses to HIV-1 Nef in mice.
AB  - The immunogenicity and efficacy of a DNA vaccine can be greatly enhanced when a
      gene adjuvant is used. LIGHT, a member of TNF superfamily, can function as a
      costimulatory molecule for human naive T cells to proliferate and can be a
      potential gene adjuvant. In the current study, the eukaryotic expression plasmid
      pcDNA-nef was constructed by inserting a full-length nef gene into pcDNA3.1(+),
      and an in vitro transfection experiment suggested that the nef gene could be
      expressed successfully in mammalian cells. BALB/c mice were immunized with HIV-1
      nef DNA vaccine plasmids alone or in combination with LIGHT expression plasmids,
      and the specific humoral and cellular immune responses were measured. The data
      showed that HIV-1 nef DNA vaccine plasmids could induce anti-Nef antibodies, Nef
      specific lymphocyte proliferation and CTL activity, whereas stronger specific
      immune responses were induced in mice when co-immunizing with HIV-1 nef DNA
      vaccine plasmids and LIGHT expression plasmids, suggesting that the eukaryotic
      expression vector encoding HIV-1 nef is capable of inducing specific immune
      responses towards HIV-1 Nef and that LIGHT could be considered as a gene adjuvant
      for HIV-1 DNA vaccination.

PMID- 24435163
TI  - Endothelial function and germ-line ACE I/D, eNOS and PAI-1 gene profiles in
      patients with coronary slow flow in the Canakkale population: multiple
      thrombophilic gene profiles in coronary slow flow.
AB  - BACKGROUND: We examined the effects of ACE, PAI-1 and eNOS gene polymorphisms on
      endothelial function. The genes are related to atherosclerosis and endothelial
      dysfunction in coronary slow flow (CSF). METHODS: Thirty-three patients with
      angiographically proven CSF and 48 subjects with normal coronary flow were
      enrolled in this study. Coronary flow patterns were determined by the
      thrombolysis in myocardial infarction (TIMI) frame count method. Endothelial
      function was assessed in the brachial artery by endothelium-dependent flow
      mediated dilatation (FMD). PAI-1 4G/5G, eNOS T-786C and ACE I/D polymorphisms
      were determined by polymerase chain reaction (PCR) amplification. RESULTS: No
      difference was found between the groups regarding age, heart rate and blood
      pressure. Males were more prevalent among patients with CSF than control subjects
      (58.8 vs 29.8%, p = 0.009). Mean TIMI frame counts were significantly higher in
      CSF patients (24.2 +/- 4.0 vs 13.1 +/- 2.5 fpm, p = 0.001). FMD was significantly
      lower in CSF patients than in the controls (4.9 +/- 6.6 vs 7.9 +/- 5.6%, p =
      0.029). TIMI frame count and FMD were found to be negatively correlated in a
      correlation analysis (r = -0.269, p = 0.015). PAI-1 4G/5G, eNOS T-786C and ACE
      I/D polymorphisms were similar in the two groups. CONCLUSIONS: This study showed
      that endothelial function was impaired in patients with CSF. PAI-1, ACE and eNOS
      polymorphisms were not related to CSF in our study population.

PMID- 24435165
TI  - Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide
      new insight into their biochemical mode of action.
AB  - The copper(II) complexes of bis-thiosemicarbazones (Cu(btsc)) such as Cu(atsm)
      and Cu(gtsm) are neutral, lipophilic compounds that show promise as therapeutics
      for the treatment of certain neurological diseases and cancers. Although the
      effects of these compounds have been described at the cellular level, there is
      almost no information about their biochemical mode of action. In this work, we
      showed that Cu(atsm) and Cu(gtsm) displayed antimicrobial activities against the
      human obligate pathogen Neisseria gonorrhoeae that were more than 100 times more
      potent than Cu(NO3)2 salt alone. Treatment with Cu(btsc) also produced phenotypes
      that were consistent with copper poisoning, but the levels of intracellular
      copper were undetectable by ICP MS. We observed that Cu(btsc) interacted with
      proteins in the cell membrane. Systematic measurements of O2 uptake further
      demonstrated that treatment with both Cu(atsm) and Cu(gtsm) led to dose-dependent
      inhibition of respiratory electron transfer processes via succinate and NADH
      dehydrogenases. These dehydrogenases were not inhibited by a non-btsc source of
      Cu(II). The results led us to conclude that the biochemical mechanism of Cu(btsc)
      action is likely more complex than the present, simplistic model of copper
      release into the cytoplasm.

PMID- 24435164
TI  - Mind the gap: can we explain declining male reproductive health with known
      antiandrogens?
AB  - Several countries have experienced rises in cryptorchidisms, hypospadias and
      testicular germ cell cancer. The reasons for these trends are largely unknown,
      but Skakkebaek has proposed that these disorders form a testicular dysgenesis
      syndrome and can be traced to androgen insufficiency in foetal life. This
      suggests that antiandrogenic chemicals might contribute to risks, but few
      chemicals have been linked to these diseases in epidemiological studies. In
      animal studies with p,p'-dichlorodiphenyldichloroethylene, effects typical of
      disruptions of male sexual differentiation became apparent when the foetal levels
      of this androgen receptor (AR) antagonist approached values associated with
      responses in in vitro assays. This prompted us to analyse whether the 22
      chemicals with AR antagonistic properties would produce mixture effects in an in
      vitro AR antagonism assay when combined at concentrations found in human serum.
      Other antiandrogenic modalities could not be considered. Two scenarios were
      investigated, one representative of average serum levels reported in European
      countries, the other in line with levels towards the high exposures. In both
      situations, the in vitro potency of the 22 selected AR antagonists was too low to
      produce combined AR antagonistic effects at the concentrations found in human
      serum, although the high exposure scenario came quite close to measurable
      effects. Nevertheless, our analysis exposes an explanation gap which can only be
      bridged by conjuring up as yet undiscovered high potency AR antagonists or,
      alternatively, high exposures to unknown agents of average potency. 

PMID- 24435166
TI  - Type I interferon plays opposing roles in cytotoxicity and interferon-gamma
      production by natural killer and CD8 T cells after influenza A virus infection in
      mice.
AB  - Type I interferons (IFNs) promote natural killer (NK) and CD8(+) T-cell
      responses, which play a role not only in the resolution of infection but also in
      the induction of acute lung injury following influenza A virus infection. We show
      here that IFN-alpha receptor knock-out (Ifnar1(-/-)) mice exhibited impaired
      cytotoxic activity as well as an increased ability of NK and CD8(+) T cells to
      produce IFN-gamma after infection with influenza virus A/FM/1/47 (H1N1, a mouse
      adapted strain). A deficiency in IFNAR signaling significantly impaired IL-10
      production in influenza virus-infected lungs and enhanced IFN-gamma production by
      NK cells, which were suppressed by exogenous IL-10. Depletion of NK cells but not
      CD8(+) T cells in Ifnar1(-/-) mice improved the survival rate after A/FM/1/47
      infection, indicating that NK cells are responsible for acute lung injury in
      Ifnar1(-/-) mice following influenza A virus infection, although the depletion of
      IFN-gamma did not improve the outcome. Thus, type I IFN signaling plays a role
      not only in the upregulation of cytotoxicity but also in the downregulation of
      some effector mechanisms including IFN-gamma production by NK and CD8(+) T cells
      via IL-10 production.

PMID- 24435167
TI  - Functional heterogeneity of PAX5 chimeras reveals insight for leukemia
      development.
AB  - PAX5, a transcription factor pivotal for B-cell commitment and maintenance, is
      one of the most frequent targets of somatic mutations in B-cell precursor acute
      lymphoblastic leukemia. A number of PAX5 rearrangements result in the expression
      of in-frame fusion genes encoding chimeric proteins, which at the N-terminus
      consistently retain the PAX5 DNA-binding paired domain fused to the C-terminal
      domains of a markedly heterogeneous group of fusion partners. PAX5 fusion
      proteins are thought to function as aberrant transcription factors, which
      antagonize wild-type PAX5 activity. To gain mechanistic insight into the role of
      PAX5 fusion proteins in leukemogenesis, the biochemical and functional properties
      of uncharacterized fusions: PAX5-DACH1, PAX5-DACH2, PAX5-ETV6, PAX5-HIPK1, and
      PAX5-POM121 were ascertained. Independent of the subcellular distribution of the
      wild-type partner proteins, ectopic expression of all PAX5 fusion proteins showed
      a predominant nuclear localization, and by chromatin immunoprecipitation all of
      the chimeric proteins exhibited binding to endogenous PAX5 target sequences.
      Furthermore, consistent with the presence of potential oligomerization motifs
      provided by the partner proteins, the self-interaction capability of several
      fusion proteins was confirmed. Remarkably, a subset of the PAX5 fusion proteins
      conferred CD79A promoter activity; however, in contrast with wild-type PAX5, the
      fusion proteins were unable to induce Cd79a transcription in a murine
      plasmacytoma cell line. These data show that leukemia-associated PAX5 fusion
      proteins share some dominating characteristics such as nuclear localization and
      DNA binding but also show distinctive features. IMPLICATIONS: This comparative
      study of multiple PAX5 fusion proteins demonstrates both common and unique
      properties, which likely dictate their function and impact on leukemia
      development.

PMID- 24435168
TI  - Haploid callus and regeneration of plants from anthers of Digitalis purpurea L.
AB  - Production of callus from anthers of D. purpurea was obtained on several basal
      media supplemented with various amounts of auxins. Chromosome counts showed that
      the callus produced was haploid when the anthers 1) were of a dark-brown to black
      color, and 2) were cultured in the late tetrad stage of microspore development.
      Subsequent differentiation to plants at high frequencies was possible only 1)
      when the anthers had been cultured on the medium of Nitsch and Nitsch (Science
      163, 85-87; 1969) supplemented with 5 mg/l 2,4-dichlorophenoxyacetic acid (2,4
      D), 2) when the callus was transferred to the same medium but without 2,4-D, and
      3) when it was cultured under continuous light from fluorescent lamps.
      Proliferation of the callus and regeneration of plants did not diminish through
      as many as 20 subcultures. The high frequency of regenerates permits the
      propagation of a distinct geno-type to a virtually unlimited number of plants.
      Diploid plants were obtained when the anthers had been cultured in the dark.
      Tetraploid plants were regenerated by callus from anthers which had been cultured
      in light. When the time of 2,4-D treatment was shortened a few haploid plants
      were produced which however did not survive transfer to soil. Cytological
      observations demonstrated that regeneration started from haploid callus, leading
      to intermediate degrees of ploidy and finally to diploid plants. Most of the
      regenerated plants were euploid and flowered and fruited normally under
      greenhouse and field conditions. If the anther-derived callus was cultured on the
      medium of Nitsch and Nitsch supplemented with 2.2 mg/l kinetin, plants
      regenerated only under photoperiodic conditions of 16 h light at 28 degrees  and
      8 h dark at 20 degrees  but the survival was lowered to one third. These plants
      had a different leaf and flower morphology as compared to the control without
      kinetin and to the starting material, but their progeny was again essentially
      normal. 

PMID- 24435169
TI  - The effect of water potential on photosynthesis in whole lichens and in their
      liberated algal components.
AB  - Experiments were performed to determine whether the fungal component of the
      lichen thallus might enable the algal component to function under conditions of
      moisture stress at which it would be unable to function if free-living. Four
      lichens were used: Lepraria membranacea Ach., Cladonia submitis Evans, Usnea
      substerilis Mot. and Letharia vulpina (L.) Hue, collected from diverse
      geographical locations. Moisture stress was quantified using the water potential
      concept, and water potential was controlled both osmotically and matrically. The
      function of the alga was evaluated by measuring photosynthesis with a (14)C
      technique. Photosynthesis of whole and ground lichen thalli was measured at
      different water potentials. Lowest water potentials permitting photosynthesis by
      whole lichen thalli ranged from-56 to-307 bar, and lowest potentials for the
      separated algal component ranged from-7 to-145 bar. In all cases the alga was
      able to photosynthesize at lower water potentials within the lichen thallus than
      when liberated. The grinding process did not harm the alga. It is suggested that
      one function of stored carbohydrate in the lichen fungus may be to increase
      internal osmotic pressure sufficiently so that the fungus thallus can absorb
      moisture from atmospheres of reduced humidity. If water secretion then occurred,
      some of this moisture could be made available to the alga. 

PMID- 24435170
TI  - Effect of osmotic stress on abscisic acid levels in xylem sap of sunflower
      (Helianthus annuus L.).
AB  - Addition of an osmoticum (-12 bars) to the rooting medium of sunflowers
      (Helianthus annuus L.) caused an increase in the level of abscisic acid (ABA)
      present in xylem exudate subsequently collected from cut shoots. Using tall and
      dwarf plants it was shown that there was a time lag in the appearance of
      increased levels of ABA in tall plants when compared with dwarf plants. The
      results indicate that the leaves, rather than the roots are the site of synthesis
      of ABA present in the xylem sap of osmotically stressed sunflower plants. 

PMID- 24435171
TI  - The occurence of ribonucleic acid in the lutoid fraction (lysosomal compartment)
      from Hevea brasiliensis Kunth. (Mull.-Arg.) latex.
AB  - The lutoids from Hevea brasiliensis latex represent a polydisperse lysosomal
      compartment. They contain RNA which is resistant to RNase in conditions which
      maintain the integrity of the lutoids but is hydrolyzed when these organelles are
      destabilized. This RNA appears to be a structural component of the lutoids. 

PMID- 24435172
TI  - Uptake of 2-[(14)C]abscisic acid by senescing leaf tissue of radish, Raphanus
      sativus L.
AB  - The uptake of [(14)C]abscisic acid by radish leaf discs rises one to two days
      after excision and then declines to six days. This pattern of uptake is not
      identical to the uptake of [(14)C]sucrose. The uptake of both [(14)C]abscisic
      acid and [(14)C]sucrose is substantially reduced by anaerobic conditions. 

PMID- 24435173
TI  - Hydrophobic cuticular ledges prevent water entering the air pores of liverwort
      thalli.
AB  - Air pore geometry of 14 liverwort species was investigated using light, scanning
      and transmission electron microscopy to assess their ability to prevent water
      entering into the air pore and the intercellular space of the thallus. The air
      pores of 12 species [Marchantia polymorpha L., M. paleacea Bertol., M. nitida
      Lindenberg & Lehmann in Lehmann, Conocephalum conicum (L.) Wiggers, C.
      supradecompositum (S.O. Lindberg) Stephani, Grimaldia capensis Stephani,
      Targionia hypophylla L., Lunularia cruciata (L.) Dum., Reboulia hemisphaerica
      (L.) Raddi, Oxymitra paleacea Bischoff, Exormotheca bullata (Link) K. Muller
      (Tub.), Plagiochasma elongatum Lindenberg & Gottsche] are equipped with
      hydrophobic ledges which constrict the air pore entrance after the fashion of an
      iris shutter. As a consequence only liquids having a contact angle of zero degree
      with the ledges are able to penetrate the air pore. The ledge of Marchantia
      paleacea was found to have a surface composed of methyl and methylene groups as
      indicated by the critical surface tension of less than 30.4 dyne cm(-1). Evidence
      is presented that the ledge is covered with a layer of cutin. It is shown that
      from the standpoint of protection against water entry these air pores must be
      considered perfect structures. Plagiochasma rupestre (Forster) Stephani and P.
      peruvianum Nees & Montagne are exceptional as they do not have ledges around
      their air pores. As a consequence liquids having a finite contact angle are able
      to enter through the pores into the thallus. Thus, they are imperfect and must be
      considered primitive. 

PMID- 24435174
TI  - [Role of some intermediates of galactosylglycerol metabolism in the osmotic
      balance in Ochromonas malhamensis].
AB  - The osmotic balance in Ochromonas malhamensis Pringsheim is achieved mainly by
      formation or degradation of alpha-galactosylglycerol (isofloridoside). The time
      course of the incorporation of radioactivity from (14)CO2 under conditions of
      high isofloridoside production suggests (Fig. 1) that isofloridoside-phosphate is
      indeed a precursor in the formation of isofloridoside. To study changes in
      relative pool sizes of intermediates cell constituents were prelabelled by
      assimilation of (14)CO2. Upon an increase of osmotic pressure the concentration
      of isofloridoside-phosphate increases rather rapidly sustaining the above
      conclusion. The final rate of isofloridoside formation, however, is reached long
      before the final concentration of the precursor is established (Fig. 2). On a
      decrease of osmotic pressure isofloridoside-phosphate concentration first
      increases and than decreases (Fig. 3). The data indicate that control of
      isofloridoside formation might occur at least at two steps: at the transfer of
      galactose to glycero-3-phosphate as well as at the dephosphorylation of
      isofloridoside-phosphate. Under conditions resulting in increased isofloridoside
      degradation the pool size of free glycerol is rapidly increased about ten fold,
      whereas the pool of free galactose responds to a far smaller extent (Fig. 3).
      This might indicate the operation of a transgalactosidase or an alpha
      galactosidase in cooperation with an unusually potent galactose kinase. 

PMID- 24435175
TI  - [Characterization and properties of two dehydroquinate hydro-lyases in higher
      plants].
AB  - Two dehydroquinate hydro-lyases (E.C. 4.2.1.10) have been routinely separated
      from different organs of Zea mays L. by chromatography on Cellex-D Bio-Rad or
      hydroxypatite using linear salt gradients. Dehydroquinate hydro-lyase 1 is
      associated with shikimate: NADP(+) oxidoreductase (E.C. 1.1.1.25). DHQase 2 is a
      free constitutive enzyme; in this respect it differs from the inducible enzyme of
      microorganisms which appears only when dehydroquinate or quinate is the principal
      carbon source. DHQase 1 and DHQase 2 have a similar apparent Michaelis constant
      and pH optimum, but they differ in their molecular weight, thermal stability and
      sensitivity to metabolic effectors. DHQase 2 is specifically activated by
      shikimic acid. This strong activation and the channeling properties of the
      complex involved in the shikimate pathway can provide an effective means of
      control in the utilization of dehydroquinate between two different pathways. The
      significance of such a system involving both a specific regulation of isoenzymes
      and a molecular compartmentation by means of an enzymatic complex is discussed. 

PMID- 24435176
TI  - The development of proteolytic activity and protein degradation during the
      germination of Pisum sativum L.
AB  - The change in protein content and composition of the cotyledons of Pisum sativum
      L. cv. Burpeeana during germination was studied. Protein depletion from the
      cotyledons was slow during the first 4 days of germination but became rapid on
      the 5th day and by the 16th day the majority of the protein had disappeared.
      During the first 4 days the depletion of the globulins exceeded that of the
      albumins; legumin appeared to be degraded slightly more rapidly than vicilin
      during the early phase of germination. Sodium-dodecylsulfate (SDS)
      electrophoresis of SDS- and dithiothreitol-dissociated globulins indicated that
      before rapid protein depletion there were marked changes in the component
      composition of the major globulins legumin and vicilin. The onset of rapid
      protein depletion was associated with an increase in the level of an acid
      sulfhydryl protease in the cotyledons. These findings indicate that the reserve
      globulins undergo modifications prior to their eventual hydrolysis. 

PMID- 24435177
TI  - Quantitative analysis of seasonal variation in the amino acids in phloem sap of
      Salix alba L.
AB  - Phloem sap of Salix alba L. was collected at monthly intervals between May and
      October. Amino acid analysis was carried out by ion exchange chromatography. The
      concentrations of individual amino acids are reported. 

PMID- 24435178
TI  - Control of branching pattern in Microgramma vacciniifolia, an epiphytic fern.
AB  - The rate of expansion of lateral buds of Microgramma vacciniifolia (Langsd. et
      Fisch) Copeland (Polypodiaceae) does not differ in intact plants, in plants with
      the rhizome apex removed, and in plants with the apex removed and replaced with
      indole-acetic acid (IAA). Root elongation is implicated in bud outgrowth possibly
      through the uptake of water and nutrients. 

PMID- 24435179
TI  - Effects of magnesium, calcium and lanthanum ions on stomatal oscillations in
      Avena sativa L.
AB  - Mg(2+), Ca(2+) and La(3+) caused an increased period time of the transpiratory
      oscillations when given to excised oscillating Avena plants (plants without root
      system). The effect was reversible, i.e. after withdrawal of the ions the period
      time returned to its original value. In order to achieve the same period
      lengthening as with 2.5 mM La(3+), 20 mM Ca(2+) and 40 mM Mg(2+) was needed. The
      effects are discussed along two lines: (a) the ions interfere with ionic
      processes, central for the stomatal regulation, and (b) the ions decrease the
      water permeability of the guard cells. Simulations on a model, previously
      published in the literature, showed that an increased resistance against the
      water flow into the guard cells could explain the findings. The ions had no
      effect on the period length of the oscillations in intact plants, i.e. with root
      system. 

PMID- 24435180
TI  - [Two peaks of plastidial DNA-synthesis with different light-dependency in the
      cell cycle of Euglena gracilis].
AB  - In the course of the life cycle of synchronized Euglena gracilis (14: 10 h light
      dark cycles) two separate peaks of plastidial DNA synthesis appear. A first
      maximum (stage I) occurs 1 to 2 hours, after initiation of the light period, the
      second maximum (stage II) 9 to 10 hours after beginning of the light period. The
      second maximum of plastidial DNA synthesis precedes the nucleic DNA synthesis by
      approximately 4 hours. DNA synthesis during stage I also takes place when
      previously synchronized cells are cultivated in darkness, whereas no DNA
      synthesis occurs during stage II in the dark. 

PMID- 24435181
TI  - In situ study of defect migration kinetics in nanoporous Ag with enhanced
      radiation tolerance.
AB  - Defect sinks, such as grain boundaries and phase boundaries, have been widely
      accepted to improve the irradiation resistance of metallic materials. However,
      free surface, an ideal defect sink, has received little attention in bulk
      materials as surface-to-volume ratio is typically low. Here by using in situ Kr
      ion irradiation technique in a transmission electron microscope, we show that
      nanoporous (NP) Ag has enhanced radiation tolerance. Besides direct evidence of
      free surface induced frequent removal of various types of defect clusters, we
      determined, for the first time, the global and instantaneous diffusivity of
      defect clusters in both coarse-grained (CG) and NP Ag. Opposite to conventional
      wisdom, both types of diffusivities are lower in NP Ag. Such a surprise is
      largely related to the reduced interaction energy between isolated defect
      clusters in NP Ag. Determination of kinetics of defect clusters is essential to
      understand and model their migration and clustering in irradiated materials. 

PMID- 24435182
TI  - Double Smiles rearrangement of Passerini adducts towards benzoxazinones.
AB  - A new straightforward access to benzoxazinones based on a three-component
      coupling is presented here. The mechanism of the whole process involves a double
      aryl transfer as clearly underlined by the X-ray diffraction analysis of the
      products. 

PMID- 24435183
TI  - How useful are blood and stool biomarkers for detecting subclinical mucosal
      inflammation in ulcerative colitis?

PMID- 24435184
TI  - SIBO in gastroparesis: sci-fi or science fact?

PMID- 24435186
TI  - Comparison of Administrative Data Versus Infection Control Data in Identifying
      Central Line-Associated Bloodstream Infections in Children's Hospitals.
AB  - OBJECTIVE: As of July 2012, the Centers for Medicare and Medicaid Services
      prohibited state Medicaid programs from paying for medical care related to
      certain provider-preventable conditions. The most prevalent provider-preventable
      condition in pediatrics is central line-associated bloodstream infections
      (CLABSIs), which cause significant morbidity and mortality. The objective of this
      study was to compare the uses of administrative data and infection control data
      in measuring CLABSIs. METHODS: Retrospective chart reviews were performed in 3
      children's hospitals to compare CLABSIs identified according to administrative
      data diagnostic coding versus infections identified by hospital infection control
      departments. Clinical criteria from the Centers for Disease Control and
      Prevention and reported to the National Healthcare Safety Network were used.
      RESULTS: A total of 166 CLABSIs were identified in 35 698 discharges in the 3
      children's hospitals in 2010. Using the Centers for Disease Control and
      Prevention criteria as the standard, administrative data had 34.78% sensitivity
      and 99.92% specificity. The positive predictive value was 63.16% whereas the
      negative predictive value was 99.75%. CONCLUSIONS: Administrative data and
      National Healthcare Safety Network criteria identify discordant numbers of
      CLABSIs.

PMID- 24435187
TI  - Moving beyond administrative data sets and coding data.

PMID- 24435185
TI  - Epistatic effects of multiple receptor genes on pathophysiology of asthma - its
      limits and potential for clinical application.
AB  - To date, genome-wide association studies (GWAS) permit a comprehensive scan of
      the genome in an unbiased manner, with high sensitivity, and thereby have the
      potential to identify candidate genes for the prevalence or development of
      multifactorial diseases such as bronchial asthma. However, most studies have only
      managed to explain a small additional percentage of hereditability estimates, and
      often fail to show consistent results among studies despite large sample sizes.
      Epistasis is defined as the interaction between multiple different genes
      affecting phenotypes. By applying epistatic analysis to clinical genetic
      research, we can analyze interactions among more than 2 molecules (genes)
      considering the whole system of the human body, illuminating dynamic molecular
      mechanisms. An increasing number of genetic studies have investigated epistatic
      effects on the risk for development of asthma. The present review highlights a
      concept of epistasis to overcome traditional genetic studies in humans and
      provides an update of evidence on epistatic effects on asthma. Furthermore, we
      review concerns regarding recent trends in epistatic analyses from the
      perspective of clinical physicians. These concerns include biological
      plausibility of genes identified by computational statistics, and definition of
      the diagnostic label of 'physician-diagnosed asthma'. In terms of these issues,
      further application of epistatic analysis will prompt identification of
      susceptibility of diseases and lead to the development of a new generation of
      pharmacological strategies to treat asthma. 

PMID- 24435188
TI  - Neonatal Abstinence Syndrome Management From Prenatal Counseling to Postdischarge
      Follow-up Care: Results of a National Survey.
AB  - OBJECTIVE: The goal of this study was to assess the current status of neonatal
      abstinence syndrome management from prenatal counseling to postdischarge follow
      up care. METHODS: An anonymous electronic survey of 26 questions was sent to the
      medical directors or charge nurses at 383 NICUs. Contact information was obtained
      by using the American Medical Association's FREIDA online database and the 2011
      American Hospital Association Guide Book. Responses were gathered by using the
      SurveyMonkey online portal, which was designed to grant responders 1-time access.
      RESULTS: There were 179 responses (47%), and 0.6%, 16.2%, and 83.2% identified
      themselves as level I, level II, and level III units, respectively. Prenatal
      counseling for at-risk mothers is offered by 56.5% of responders. Written
      protocols for neonatal abstinence syndrome management were reported by 72.5%. All
      but 3 institutions used toxicology screening in cases of suspected in utero drug
      exposure. Formalized scoring is used by 98.7%. Breastfeeding is recommended by
      74.1%. Morphine (56.1%), methadone (24.8%), and tincture of opium (12.7%) are the
      most common first-line agents reported in opiate withdrawal, whereas morphine
      (51.0%), methadone (19.7%), and phenobarbital (13.6%) are used in polydrug
      withdrawal. Less than 20% of NICUs use clonidine. Home treatment programs are
      offered by 34.0% of responders, and long-term developmental follow-up is offered
      by 71.3%. CONCLUSIONS: There is considerable diversity in the management of
      neonatal abstinence syndrome. Alternative management strategies, including
      prenatal counseling and home treatment programs, need to be explored to improve
      overall patient care.

PMID- 24435189
TI  - Neonatal abstinence syndrome and the pediatric hospitalist.

PMID- 24435190
TI  - Connecting at-risk inpatient asthmatics to a community-based program to reduce
      home environmental risks: care system redesign using quality improvement methods.
AB  - INTRODUCTION: Connecting patients admitted with asthma to community-based
      services could improve care and more efficiently allocate resources. We sought to
      develop and evaluate an intervention to mitigate in-home environmental hazards
      (eg, pests, mold) for such children. METHODS: This was a controlled, quality
      improvement study on the inpatient units of an urban, academic children's
      hospital. Clinicians and public health officials co-developed processes to
      identify children with in-home risks and refer them for assessment and
      remediation. Processes assessed were the rate at which those identified as
      eligible were offered referrals, those referred received inspections, and primary
      care physicians (PCPs) were notified of risks and referrals. Consecutively
      occurring and seasonally matched intervention (n = 30) and historical control (n
      = 38) subcohorts were compared with respect to postdischarge mitigating actions
      (eg, discussions with landlords, PCPs), remaining risks, and morbidity (symptom
      free days in previous 2 weeks and Child Asthma Control Test scores). RESULTS: In
      the first year, the percentage of eligible children offered referrals increased
      to a sustained rate of ~90%; ~65% of referrals led to in-home inspections (n =
      50); and hazards were abated in 30 homes. PCP notification increased from 50% to
      ~80%. After discharge, referred parents were more likely to discuss concerns with
      landlords, the health department, attorneys, and PCPs than patients admitted
      preimplementation (all P < .05). Referred households were more likely to report
      reduced presence of >=2 exposures (P < .05). No differences in asthma morbidity
      were observed. CONCLUSIONS: We integrated environmental hazard mitigation into
      inpatient care. Community-engaged care delivery that reduces risks for poor
      asthma outcomes can be initiated within the hospital.

PMID- 24435191
TI  - Practice Variance, Prevalence, and Economic Burden of Premature Infants Diagnosed
      With GERD.
AB  - OBJECTIVE: To determine the practice variance, prevalence, and economic burden of
      clinically diagnosed gastroesophageal reflux disease (GERD) in preterm infants.
      METHODS: Applying a retrospective cohort study design, we analyzed data from 18
      567 preterm infants of 22 to 36 weeks' gestation and >400 g birth weight from the
      NICUs of 33 freestanding children's hospitals in the United States. GERD
      prevalence, comorbidities, and demographic factors were examined for their
      association with average length of stay (LOS) and hospitalization cost. RESULTS:
      Overall, 10.3% of infants received a diagnosis of GERD (95% confidence interval
      [CI]: 9.8-10.7). There was a 13-fold variation in GERD rates across hospitals (P
      < .001). GERD diagnosis was significantly (P < .05) associated with
      bronchopulmonary dysplasia and necrotizing enterocolitis, as well as congenital
      anomalies and decreased birth weight. GERD diagnosis was associated with $70 489
      (95% CI: 62 184-78 794) additional costs per discharge and 29.9 additional days
      in LOS (95% CI: 27.3-32.5). CONCLUSIONS: One in 10 of these premature NICU
      infants were diagnosed with GERD, which is associated with substantially
      increased LOS and elevated costs. Better diagnostic and management strategies are
      needed to evaluate reflux-type symptoms in this vulnerable NICU population.

PMID- 24435192
TI  - Procedural sedation by pediatric hospitalists: analysis of the nature and
      incidence of complications during ketamine and nitrous oxide sedation.
AB  - OBJECTIVE: The goal of this study was to determine the nature and rate of
      complications during procedural sedation by pediatric hospitalists (PH) using
      ketamine and nitrous oxide (N2O). METHODS: This study was a retrospective review
      and analysis of a quality improvement database for sedations performed by PH at
      St Louis Children's Hospital from February 2007 to February 2013. Information was
      obtained on sedations performed and reported in the quality improvement database
      by PH over this time period using ketamine and N2O. RESULTS: PH performed 8870
      sedations from 2007 to 2013, 60.2% using ketamine and 39.8% using N2O. Procedural
      completion rates were >99%; 0.12% of sedations were not completed due to
      inadequate sedation, and sedation level was not achieved in 1.71% of sedations.
      There were no occurrences of death, need for cardiopulmonary resuscitation,
      unplanned intubation, or emergency anesthesia consultation. The only major
      complications were 4 unplanned admissions, 2 each with ketamine and N2O. With
      ketamine, the 2 highest rates of complications were airway repositioning (3.99%)
      and nausea and/or vomiting (2.98%). With N2O, the 2 highest complication rates
      were nausea and/or vomiting (8.50%) and airway repositioning (1.10%). Respiratory
      and cardiovascular events were more frequently encountered with ketamine, whereas
      nausea/vomiting, sedation level not achieved, and inadequate sedation resulting
      in procedure not completed occurred more frequently with N2O. CONCLUSIONS: PH at
      St Louis Children's Hospital successfully provided sedation by using ketamine and
      N2O with low rates of complications for a variety of procedures.

PMID- 24435193
TI  - Ruling out bacteremia and bacterial meningitis in infants less than one month of
      age: is 48 hours of hospitalization necessary?
AB  - OBJECTIVE: The appropriate duration of hospitalization for infants <= 30 days
      admitted for fever or other concerns for a serious bacterial infection is an
      understudied area. We sought to determine the risk of a positive, pathogenic
      bacterial culture of blood or cerebrospinal fluid (CSF) in this population beyond
      24 hours after collection. METHODS: This study was a retrospective review of 1145
      infants aged <=30 days who had a blood or CSF culture from 1999 to 2010 at Santa
      Clara Valley Medical Center, a county health system in San Jose, California. Time
      to notification and the probability of a positive culture result after 24 hours
      were calculated. Infants were considered high risk if they had either a white
      blood cell count <5000 or >15 000 per uL, a band count >1500 per uL, or an
      abnormal urinalysis. RESULTS: We identified 1876 cultures (1244 blood, 632 CSF)
      in 1145 infants aged <=30 days; 901 (79%) of 1145 were hospitalized and 408 (45%)
      of 901 hospitalizations were for fever without source (FWS). Thirty-one (2.7%) of
      the 1145 infants had pathogenic cultures; 6 of 1145 infants (0.5% [95% confidence
      interval: 0.2-1.1]) had a time to notification >24 hours. All 6 patients had FWS
      (1.5% of hospitalized FWS sample) and met high-risk criteria on presentation. No
      low-risk patients had a time to notification >24 hours. Low-risk characteristics
      were found in 57% (232 of 408) of the entire hospitalized FWS population.
      CONCLUSIONS: Low-risk infants hospitalized for FWS or other concerns for serious
      bacterial infection may not need hospitalization for a full 48 hours simply to
      rule out bacteremia and bacterial meningitis.

PMID- 24435194
TI  - Neonatal circumcision: is feeding behavior altered?
AB  - BACKGROUND: The effect of circumcision on feeding behavior in the newborn period
      is unknown. We hypothesized that circumcision would not have a significant effect
      on newborn feeding. METHODS: This prospective study analyzed the effect of
      circumcision on neonatal feeding behavior. Inclusion criteria were healthy male
      infants WHO were exclusively bottle-fed and underwent a circumcision before
      discharge from the newborn nursery. We collected data (N = 42) on gestational
      age, birth weight, Apgar scores, maternal age, gravid status, anesthesia used
      during delivery, analgesia used after circumcision, time of circumcision, and
      volume and frequency of feeding before and after circumcision. Data were analyzed
      by using paired t tests, multivariable regression analysis, and analysis of
      variance (with SPSS version 18). Significance was P < .05 (2-tailed alpha).
      RESULTS: Descriptive statistics for the entire group (N = 42) are as follows:
      mean +/- SD gestational age: 38.7 +/- 1.2 weeks; mean birth weight: 3.3 +/- 0.4
      kg; maternal age: 26.7 +/- 6.3 years; baseline feeding (mean of first 2 feedings
      before circumcision): 24.5 +/- 9.9 mL; mean first feeding after circumcision:
      21.7 +/- 11.9 mL; and mean second feeding: 26.7 +/- 13.5 mL. Forty-eight percent
      of patients increased their feeding volume after circumcision compared with
      baseline, and 52% of patients decreased their feeding volume, which persisted
      with the second feeding. There was no statistical difference between the baseline
      and first feeding (P = .11) or second feeding (P = .22). CONCLUSIONS: Our data
      suggest that circumcision does not alter feeding after circumcision. This
      information will be useful in counseling families regarding circumcision in the
      newborn period.

PMID- 24435195
TI  - Association of NPO Status and Type of Nutritional Support on Weight and Length of
      Stay in Infants Hospitalized With Bronchiolitis.
AB  - OBJECTIVES: We investigated the association of nil per os (NPO) status and
      subsequent nutritional support with patient weight and length of stay (LOS)
      during admission for bronchiolitis in patients <2 years old. METHODS: A
      retrospective chart review was performed of all patients <2 years old admitted to
      an academic pediatric hospital between November 2009 and June 2011 with a Current
      Procedural Terminology code of bronchiolitis. Data extracted from the medical
      record included respiratory rate, per os/NPO status, use of intravenous fluids,
      use of enteral tube feedings, weight, and LOS. Patients who did not have 2
      weights recorded were excluded. The major outcome measures were weight change
      during admission and LOS. RESULTS: The study included 149 patients. The mean +/-
      SD patient age was 3.7 +/- 3.8 months, with a median age of 2 months. The median
      length of stay was 4 days (interquartile range: 3-6). Overall, 16% of patients
      were made NPO, 75% received intravenous fluids, and 9% received enteral tube
      feedings. The mean weight loss for all patients was 38 (289) g during the
      hospitalization, which was not statistically significant. No significant
      association was found between weight loss and LOS, per os/NPO status, or use of
      intravenous fluids. However, NPO status was associated with a significant
      increase in LOS. CONCLUSIONS: The infants admitted for bronchiolitis did not
      demonstrate weight loss in this study; however, an association was seen between
      NPO status and prolonged LOS.

PMID- 24435196
TI  - Vitamin d in pediatric inpatients with respiratory illnesses.
AB  - BACKGROUND AND OBJECTIVE: Low serum 25-hydroxyvitamin D (25[OH]D) levels have
      been associated with increased susceptibility to and severity of respiratory
      viral infections. Hypovitaminosis D may be a modifiable risk factor in the
      severity of viral respiratory illnesses. The hypothesis for this study was that
      children hospitalized for respiratory illnesses would have lower serum 25(OH)D
      levels than controls and that 25(OH)D levels would be associated with illness
      severity among cases. METHODS: A case-control study of a sample of patients aged
      6 months through 12 years hospitalized from January to May 2010 at an urban
      pediatric referral hospital was performed. Cases were children hospitalized for
      acute respiratory illnesses, and controls were children hospitalized for
      nonrespiratory illnesses. Illness severity among cases was assessed according to
      hospital length of stay, ICU admission, peripheral oxygen saturation, and
      pediatric risk of admission II score. Associations between serum 25(OH)D levels
      and dependent variables were tested for by using binary logistic and
      multivariable linear regression while controlling for admission diagnosis, age,
      gender, and race/ethnicity. RESULTS: The majority of cases (n = 38) and controls
      (n = 83) were African American (65.8% and 59.0%, respectively). Of the entire
      cohort (N = 121), 64.8% had vitamin D insufficiency (25[OH]D level <=30 ng/mL)
      and 31.1% had vitamin D deficiency (25[OH]D level <=20 ng/mL). Mean +/- SD
      25(OH)D levels did not differ between cases and controls (26.8 +/- 11.5 vs 26.1
      +/- 10.6 ng/mL, respectively; P = .73). CONCLUSIONS: Hypovitaminosis D was common
      among cases and controls, but it was not significantly associated with the
      presence or severity of respiratory illnesses.

PMID- 24435197
TI  - A diagnosis of exclusion: a 3-year-old boy with respiratory distress and anemia.

PMID- 24435198
TI  - A proposed mechanism to assess knowledge of pediatric hospitalists to identify
      and manage rare events during procedural sedation.
AB  - OBJECTIVE: The goal of this study was to assess the knowledge of pediatric
      hospitalists (PHs) in identifying and managing rare events during procedural
      sedation (PS) with ketamine and nitrous oxide (N2O). METHODS: A Web-based survey
      with multiple choice questions and case scenarios was used to determine the
      knowledge of PHs in identifying infrequent contraindications and managing
      laryngospasm, a rare life-threatening complication during PS. The survey was sent
      to all PHs at St Louis Children's Hospital. RESULTS: Forty percent of experienced
      PHs (>50 sedation procedures performed) and 5% of inexperienced PHs (<50 sedation
      procedures performed) identified all 4 ketamine contraindications. Twenty-one
      percent of experienced PHs and 4% of inexperienced PHs identified all 6 N2O
      contraindications. Ninety-five percent of PHs identified presence of laryngospasm
      in a case scenario. As the patient in the case scenario progressed from partial
      to complete laryngospasm, 84% and 82% of PHs chose either the preferred or
      acceptable strategy to manage the patient. With further deterioration in the
      patient's status in the scenario, 66% and 71% of PHs chose either the preferred
      or acceptable strategy to manage the patient. The preferred strategy at each step
      is one that attempted the least invasive maneuver to manage the patient. There
      was no significant difference between experienced and inexperienced PHs in the
      management of laryngospasm. CONCLUSIONS: Knowledge gaps exist among PHs regarding
      contraindications for ketamine and N2O that are infrequently encountered in
      patients and for the management of laryngospasm, a rare adverse event with
      ketamine. Ongoing teaching tools are necessary to assess and maintain the
      knowledge of sedation providers regarding rare events during PS that can improve
      their proficiency.

PMID- 24435199
TI  - Silly rabbit! Brightly colored sugary rice cereal is for kids -- or is it?

PMID- 24435200
TI  - Section on hospital medicine leadership and staff.

PMID- 24435202
TI  - What's new in the controversy on the renal/tissue toxicity of starch solutions?

PMID- 24435201
TI  - One-year mortality and predictors of death among hospital survivors of acute
      respiratory distress syndrome.
AB  - PURPOSE: Advances in supportive care and ventilator management for acute
      respiratory distress syndrome (ARDS) have resulted in declines in short-term
      mortality, but risks of death after survival to hospital discharge have not been
      well described. Our objective was to quantify the difference between short-term
      and long-term mortality in ARDS and to identify risk factors for death and causes
      of death at 1 year among hospital survivors. METHODS: This multi-intensive care
      unit, prospective cohort included patients with ARDS enrolled between January
      2006 and February 2010. We determined the clinical characteristics associated
      with in-hospital and 1-year mortality among hospital survivors and utilized death
      certificate data to identify causes of death. RESULTS: Of 646 patients
      hospitalized with ARDS, mortality at 1 year was substantially higher (41 %, 95%
      CI 37-45%) than in-hospital mortality (24%, 95% CI 21-27%), P < 0.0001. Among 493
      patients who survived to hospital discharge, the 110 (22%) who died in the
      subsequent year were older (P < 0.001) and more likely to have been discharged to
      a nursing home, other hospital, or hospice compared to patients alive at 1 year
      (P < 0.001). Important predictors of death among hospital survivors were
      comorbidities present at the time of ARDS, and not living at home prior to
      admission. ARDS-related measures of severity of illness did not emerge as
      independent predictors of mortality in hospital survivors. CONCLUSIONS: Despite
      improvements in short-term ARDS outcomes, 1-year mortality is high, mostly
      because of the large burden of comorbidities, which are prevalent in patients
      with ARDS.

PMID- 24435204
TI  - Improved ICU outcomes in ARDS patients: implication on long-term outcomes.

PMID- 24435203
TI  - Prone positioning reduces mortality from acute respiratory distress syndrome in
      the low tidal volume era: a meta-analysis.
AB  - PURPOSE: Prone positioning for ARDS has been performed for decades without
      definitive evidence of clinical benefit. A recent multicenter trial demonstrated
      for the first time significantly reduced mortality with prone positioning. This
      meta-analysis was performed to integrate these findings with existing literature
      and test whether differences in tidal volume explain conflicting results among
      randomized trials. METHODS: Studies were identified using MEDLINE, EMBASE,
      Cochrane Register of Controlled Trials, LILACS, and citation review. Included
      were randomized trials evaluating the effect on mortality of prone versus supine
      positioning during conventional ventilation for ARDS. The primary outcome was
      risk ratio of death at 60 days meta-analyzed using random effects models.
      Analysis stratified by high (>8 ml/kg predicted body weight) or low (<= 8 ml/kg
      PBW) mean baseline tidal volume was planned a priori. RESULTS: Seven trials were
      identified including 2,119 patients, of whom 1,088 received prone positioning.
      Overall, prone positioning was not significantly associated with the risk ratio
      of death (RR 0.83; 95% CI 0.68-1.02; p = 0.073; I (2) = 64%). When stratified by
      high or low tidal volume, prone positioning was associated with a significant
      decrease in RR of death only among studies with low baseline tidal volume (RR
      0.66; 95% CI 0.50-0.86; p = 0.002; I (2) = 25%). Stratification by tidal volume
      explained over half the between-study heterogeneity observed in the unstratified
      analysis. CONCLUSIONS: Prone positioning is associated with significantly reduced
      mortality from ARDS in the low tidal volume era. Substantial heterogeneity across
      studies can be explained by differences in tidal volume.

PMID- 24435205
TI  - Fate and transformation of naphthylaminesulfonic azo dye reactive black 5 during
      wastewater treatment process.
AB  - Certain aromatic amines generated by the decolorization of some azo dyes are not
      removed substantially by conventional anaerobic-aerobic biotreatment. These
      aromatic amines are potentially toxic and often released in the wastewater of
      industrial plants. In this study, the fate and transformation of the
      naphthylaminesulfonic azo dye Reactive Black 5 (RB5) during different phases of a
      sequencing batch reactor were investigated. The major products of RB5
      decolorization during the anaerobic phase include 2-[(4
      aminophenyl)sulfonyl]ethyl hydrogen sulfate (APSEHS) and 1-2-7-triamino-8-hydroxy
      3-6-naphthalinedisulfate (TAHNDS). During the aerobic phase, APSEHS was
      hydrolyzed and produced 4-aminobenzenesulfonic acid, which was further degraded
      via dearomatization. TAHNDS was transformed rapidly via auto-oxidation into
      TAHNDSDP-1 and TAHNDSDP-2, which were not further removed by the activated sludge
      during the entire 30-day aerobic phase. In contrast, different behaviors of
      TAHNDS were observed during the anoxic phase. The transformation of TAHNDS was
      initiated either by deamination or desulfonation reaction. TAHNDS was then
      converted into 3,5-diamino-4-hydroxynaphthalene-2-sulfonic acid, which was
      subsequently removed via ring cleavage reaction under aerobic condition. In
      conclusion, complete degradation of TAHNDS by activated sludge occurs only during
      anoxic/aerobic processes instead of the conventional anaerobic/aerobic processes.

PMID- 24435206
TI  - Short- and long-term treatment of mouse cortical primary astrocytes with beta
      amyloid differentially regulates the mRNA expression of L-type calcium channels.
AB  - BACKGROUND: It is well established that reactive astrocytes express L-type
      calcium channels (LTCC), but their functional role is completely unknown. We have
      recently shown that reactive astrocytes highly express the CaV1.2 alpha1-subunit
      around beta-amyloid (Abeta) plaques in an Alzheimer mouse model. The aim of the
      present study was to explore whether Abeta peptides may regulate the mRNA
      expression of all LTCC subunits in primary mouse astrocytes in culture. METHODS:
      Confluent primary astrocytes were incubated with 10 ug/ml of human or murine
      Abeta or the toxic fragment Abeta25-35 for 3 days or for 3 weeks. The LTCC
      subunits were determined by quantitative RT-PCR. RESULTS: Our data show that
      murine Abeta42 slightly but significantly increased CaV1.2 and CaV1.3 expression
      when incubated for 3 days. This acute treatment with murine Abeta enhanced beta2
      and beta3 mRNA levels but decreased alpha2delta-2 mRNA expression. When
      astrocytes were incubated for 3 weeks, the levels of CaV1.2 alpha1 were
      significantly decreased by the murine Abeta and the toxic fragment. As a control,
      the protein kinase C-epsilon activator DCP-LA displayed a decrease in CaV2.1
      expression. CONCLUSION: In conclusion, our data show that Abeta can
      differentially regulate LTCC expression in primary mouse astrocytes depending on
      incubation time.

PMID- 24435208
TI  - Synthesis of tetracyclic chromenones via platinum(II) chloride catalysed cascade
      cyclization of enediyne-enones.
AB  - PtCl2 catalysed cascade cyclization of an enediyne-enone system to afford a
      tetracyclic chromenone is reported, which proceeds through two consecutive highly
      regioselective 6-endo-dig cyclizations in a single step with the formation of two
      new C-C bonds and two new rings in excellent yield. A mechanism for this
      transformation is proposed based on the isolated intermediates. 

PMID- 24435207
TI  - Efficacy of silodosin in patients undergoing brachytherapy: a randomized trial
      involving a pressure flow study.
AB  - PURPOSE: The purpose of the study is to investigate the efficacy of an alpha-1
      adrenergic receptor antagonist (silodosin) for the treatment of lower urinary
      tract symptoms (LUTS) associated with interstitial (125)I implantation for
      prostate cancer. METHODS: This randomized single-center study involved 105
      patients (53 with and 52 without silodosin). Silodosin was postoperatively
      administered, daily, for 6 months (8 mg/day). Urinary symptoms and pressure flow
      were evaluated preoperatively and postoperatively at 1, 3, 6, and 12 months.
      RESULTS: At 12 months, interstitial (125)I implantation had induced a significant
      decrease in prostate volume (28.3 +/- 11.1-20.5 +/- 8.1 g in the silodosin group
      and 26.1 +/- 9.7-17.7 +/- 4.9 g in the controls) and the prostate-specific
      antigen level (7.1 +/- 3.6-1.4 +/- 1.7 ng/mL in the silodosin group and 8.1 +/-
      4.3-1.3 +/- 1.2 ng/mL in the controls). Significant improvements in the
      international prostate symptom voiding subscores at 6 months and quality of life
      at 3 months were observed in those receiving silodosin. The pressure flow studies
      demonstrated that silodosin had significantly enlarged the bladder capacity when
      the first non-voiding contraction was seen at 3 and 12 months (3M: 127.1 +/- 74.8
      vs. 118.2 +/- 83.9 mL, p = 0.001; 12M: 123.7 +/- 79.3 vs. 100.3 +/- 73.4 mL, p =
      0.01); however, there were no improvements in the bladder outlet obstruction
      index (BOOI) or urinary flow. CONCLUSIONS: Silodosin temporarily improved LUTS,
      but did not improve the BOOI after (125)I implantation in the prostate.

PMID- 24435209
TI  - New materials for tunable plasmonic colloidal nanocrystals.
AB  - We present a review on the emerging materials for novel plasmonic colloidal
      nanocrystals. We start by explaining the basic processes involved in surface
      plasmon resonances in nanoparticles and then discuss the classes of nanocrystals
      that to date are particularly promising for tunable plasmonics: non
      stoichiometric copper chalcogenides, extrinsically doped metal oxides, oxygen
      deficient metal oxides and conductive metal oxides. We additionally introduce
      other emerging types of plasmonic nanocrystals and finally we give an outlook on
      nanocrystals of materials that could potentially display interesting plasmonic
      properties. 

PMID- 24435210
TI  - Ultrathin rhodium nanosheets.
AB  - Despite significant advances in the fabrication and applications of graphene-like
      materials, it remains a challenge to prepare single-layered metallic materials,
      which have great potential applications in physics, chemistry and material
      science. Here we report the fabrication of poly(vinylpyrrolidone)-supported
      single-layered rhodium nanosheets using a facile solvothermal method. Atomic
      force microscope shows that the thickness of a rhodium nanosheet is <4 A.
      Electron diffraction and X-ray absorption spectroscopy measurements suggest that
      the rhodium nanosheets are composed of planar single-atom-layered sheets of
      rhodium. Density functional theory studies reveal that the single-layered Rh
      nanosheet involves a delta-bonding framework, which stabilizes the single-layered
      structure together with the poly(vinylpyrrolidone) ligands. The
      poly(vinylpyrrolidone)-supported single-layered rhodium nanosheet represents a
      class of metallic two-dimensional structures that might inspire further
      fundamental advances in physics, chemistry and material science. 

PMID- 24435213
TI  - Quantitative genetics of sugarcane : II. Correlation analysis of continuous
      characters in relation to hybrid sugarcane breeding.
AB  - 1. A study has been made of the genetic, clonal and environmental correlations
      existing among commercially important characters in a sugarcane breeding
      population of interspecific hybrid origin. 2. In general, there is a close
      correspondence between genetic correlation coefficients measuring the extent of
      association at the level of family means, and clonal correlations measuring
      genotypic relationships at the level of clone means. Greater weight has therefore
      been given to the numerical estimates of the clonal correlations, in view of
      their greater accuracy, and the possibility that atypical family groups may
      unduly influence the genetic correlations. 3. Many significant environmental
      correlations, generally of a low order of magnitude, have been detected. These
      have been found to fall naturally into a pattern based on the operation of
      factors causing differences from plot-to-plot in either growth rate or the
      process of ripening. 4. A wide variety of genetic relationships cannot be
      explained in terms of these same two physiological processes. The signs of the
      clonal correlation coefficients for these particular associations fall very
      clearly into a pattern identical with that distinguishing the wild species from
      Saccharum officinarum. 5. The cytological basis for this partial retention of
      original parent species associations is almost certainly the segregation of whole
      chromosomes from the wild species as intact units, with little possibility of
      gene exchange or recombination with chromosomes from S. officinarum. 6. The
      magnitudes of the observed clonal correlations in general indicate ample scope
      for independent genetic manipulation of traits from wild and noble canes,
      provided selection pressure is maintained on all those of commercial importance.
      However, the interrelationships involving number of stalks per plot, stalk cross
      sectional area and fibre percent fresh weight, are somewhat more restrictive. 7.
      Attention is drawn to the need for a more extensive sampling of the genetic
      variation available within the wild species S. spontaneum, S. robustum and S.
      sinense. 

PMID- 24435212
TI  - Light-regulated phosphorylation of maize phosphoenolpyruvate carboxykinase plays
      a vital role in its activity.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK)-the major decarboxylase in PEPCK-type
      C4 plants-is also present in appreciable amounts in the bundle sheath cells of
      NADP-malic enzyme-type C4 plants, such as maize (Zea mays), where it plays an
      apparent crucial role during photosynthesis (Wingler et al., in Plant Physiol
      120(2):539-546, 1999; Furumoto et al., in Plant Mol Biol 41(3):301-311, 1999).
      Herein, we describe the use of mass spectrometry to demonstrate phosphorylation
      of maize PEPCK residues Ser55, Thr58, Thr59, and Thr120. Western blotting
      indicated that the extent of Ser55 phosphorylation dramatically increases in the
      leaves of maize seedlings when the seedlings are transferred from darkness to
      light, and decreases in the leaves of seedlings transferred from light to
      darkness. The effect of light on phosphorylation of this residue is opposite that
      of the effect of light on PEPCK activity, with the decarboxylase activity of
      PEPCK being less in illuminated leaves than in leaves left in the dark. This
      inverse relationship between PEPCK activity and the extent of phosphorylation
      suggests that the suppressive effect of light on PEPCK decarboxylation activity
      might be mediated by reversible phosphorylation of Ser55. 

PMID- 24435214
TI  - [A rapid method for the simultaneous determination of beta-amylase and protein
      content of barley and the heritability of these traits in an experiment with 16
      varieties of malting barley].
AB  - 1. A rapid method for simultaneous determination of beta-amylase and protein
      content in malting barley was developed. 500 mg of flour are shaken up with a
      cysteine containing activation solution and the suspension is mixed directly with
      the enzyme substrate. The aldoses in the supernatent are titrated iodometrically,
      and the proteins dissolved in alkaline solution are Kjeldahl digested and
      nesslerized in the same test tube. 2. Samples of the 16 varieties used for the
      official Czechoslovakian State trials, grown at 4 different localities were
      analyzed and the results compared with the official ones. 3. By an analysis of
      variance the following standard errors, including analytical and trial errors,
      were estimated: For the official nitrogen content and beta-amylase determination
      3.2% and 9.7% respectively, compared with 6.5% each by rapid method determination
      of beta-amylase and nitrogen, in terms of the measured value. The standard
      analytical error of the rapid determination of nitrogen and beta-amylase content
      was 2.4% and 3.1% respectively. 4. Both analytical methods showed the locality
      differences to have the greatest effect on the variability of both traits; and
      affected each to the same extent. No varietal differences in nitrogen content
      could be demonstrated but considerable genetic variability of beta-amylase
      content was found by both analytical methods. 5. In the 64 barley samples tested
      the heritability of beta-amylase was estimated as 0.37. The sum of the locality
      and variety variance was taken as the population variance. Within localities the
      genetic variance was 41.6 and 51.5% of the total variance of beta-amylase values
      obtained by means of the official and rapid method, respectively. 6. The rapid
      method supplies at least as much useful information as the official method, and
      can be used for the purpose of selection. 

PMID- 24435215
TI  - Stamina pistilloida: a new mutation induced in pea.
AB  - After diethylsulphate treatment of seeds of the pea variety 'Parvus', a new
      floral mutation was isolated in the second generation. This mutation, named
      stamina pistilloida, is characterized by a partial fusion of the androecium with
      the gynoecium; the two marginal stamens of the staminal column are transformed in
      rudimentary carpels more or less differentiated according to ecoclimatic
      conditions. The genetic analysis has shown the monogenic and recessive behaviour
      of the mutation (gene proposed stp) and its linkage with the gene oh in the
      chromosome II. 

PMID- 24435216
TI  - [Testing of potato varieties for resistance and resistance behavior to virus S].
AB  - 1. Experimental infections with virus S on a number of varieties showed that
      serological tests performed on the plant failed to prove a new infection with
      certainty. Such new infection remains symptomless, while invasion of the tuber
      proceeds relatively rapidly. 2. During the last three years 67 varieties were
      tested : 22.4 percent were found to be of low, 47.8 percent of medium, and 29.8
      percent of high resistance. 3. The rate of tuber contamination of a primary
      infected plant increased from resistance stage 1 with 37.9 percent virus
      infection to 83.0 percent in resistance stage 9. With the degree of resistance
      the portion of noninfected plants decreased, that of 100 percent infected plants
      increased. Symptomatologically, there was almost total latency after secondary
      infections; only in a few cases were non-uniform and varying symptoms observed.
      4. The potato plant has a well defined mature plant resistance to virus S. There
      are practically no differences in the degree of infection conferred to older,
      unequally resistant varieties, so that inoculation must be done at an early age
      when resistance differences are to be recorded. 5. The resistance tests of 1964
      1967 used different methods of inoculation. Rubbing the virus-containing sap on
      one leaf of each sprout resulted in a low degree of infection, inoculation by
      spray gun in a high one. From a comparison of the different years and methods of
      infection one may conclude that the resistance of a variety can be reliably
      reproduced if one half of the plants are inoculated by rubbing, the other half by
      spray gun. A medium degree of infection and good differentiation of the varieties
      can thus be obtained. 6. Only with late manual inoculation of a highly
      susceptible variety did early lifting result in a remarkable decrease of
      infection. As the result of mature plant resistance such an effect was prevented
      in potatoes of medium susceptibility. 

PMID- 24435217
TI  - Studies of inheritance of reaction to common smut in corn.
AB  - Reaction to Ustilago maydis was studied in resistant and susceptible corn
      inbreds, their F 1 hybrids and F 2 and F 3 segregants. Marked differences among
      inbreds in genetic prepotency were found. Segregation was polygenic. The concept
      of combining ability was applied and estimates of sigma G (/2) and sigma S (/2)
      were calculated. Both additive and non-additive gene action was found. Breeding
      for resistance based on crossing to special susceptible testers was suggested. 

PMID- 24435218
TI  - Tuber proteins from haploids, selfs, and cultivars of group tuberosum separated
      by acid gel disc electrophoresis.
AB  - Tuber extracts of 46 cultivars (American varieties), and 350 haploids (2n=24) and
      selfs (2n=48) from four parents (2n=48), were analysed by acid gel disc
      electrophoresis. This system separated proteins into 12-14 bands. Twelve
      cultivars possessed unique patterns of bands, and the remaining cultivars could
      be placed in groups on the basis of 8 different banding patterns. Distinctions
      between varieties within groups was accomplished by either esterase or peroxidase
      isozyme patterns. The usefulness of basic gel proteins, esterase, and peroxidases
      for varietal identification is known; the acid gel protein patterns described
      provide a fourth system.Proteins from haploids and selfs were examined for
      variation in frequency and presence of bands. Differences among bands of the 4
      parents were minor. Most haploids and selfs possessed the same bands as their
      parents, but there were interesting exceptions. The frequency of certain bands
      was significantly higher in selfs than in haploids. The results fit what would be
      expected if the parent tetraploid is simplex for a dominant allele controlling
      the production of each protein. Other bands are more frequent in haploids than
      selfs and some bands are present in haploids and not in the parent. Suppressor
      genes in the tetraploids may account for these latter results. 

PMID- 24435219
TI  - Yellow NIR dye: pi-fused bisbenzoBODIPYs with electron-withdrawing groups.
AB  - Bicyclo[2.2.2]octadiene-fused (BCOD-fused) bis(benzoborondipyrromethene)s
      (bisbenzoBODIPYs) bearing electron-withdrawing groups such as fluorine and cyano
      groups were prepared either by incorporating tetrafluoroisoindole moieties into
      BODIPY chromophores or by introducing cyano or ethoxycarbonyl groups at the 3,5
      positions. The BCOD-fused bisbenzoBODIPYs were quantitatively converted to the
      corresponding benzene-fused bisbenzoBODIPYs by a retro-Diels-Alder reaction. The
      pi-fused bisbenzoBODIPYs were found to have intense absorption in the near
      infrared region and not to have any strong absorption bands in the visible
      region. Moreover, the bisbenzoBODIPYs were stable under atmospheric conditions. 

PMID- 24435220
TI  - A meta-analysis comparing the sensitivity of bees to pesticides.
AB  - The honey bee Apis mellifera, the test species used in the current environmental
      risk assessment procedure, is generally considered as extremely sensitive to
      pesticides when compared to other bee species, although a quantitative approach
      for comparing the difference in sensitivity among bees has not yet been reported.
      A systematic review of the relevant literature on the topic followed by a meta
      analysis has been performed. Both the contact and oral acute LD50 and the chronic
      LC50 reported in laboratory studies for as many substances as possible have been
      extracted from the papers in order to compare the sensitivity to pesticides of
      honey bees and other bee species (Apiformes). The sensitivity ratio R between the
      endpoint for the species a (A. mellifera) and the species s (bees other than A.
      mellifera) was calculated for a total of 150 case studies including 19 bee
      species. A ratio higher than 1 indicated that the species s was more sensitive to
      pesticides than honey bees. The meta-analysis showed a high variability of
      sensitivity among bee species (R from 0.001 to 2085.7), however, in approximately
      95 % of the cases the sensitivity ratio was below 10. The effect of pesticides in
      domestic and wild bees is dependent on the intrinsic sensitivity of single bee
      species as well as their specific life cycle, nesting activity and foraging
      behaviour. Current data indicates a need for more comparative information between
      honey bees and non-Apis bees as well as separate pesticide risk assessment
      procedures for non-Apis bees. 

PMID- 24435221
TI  - Valgus bracing in symptomatic varus malalignment for testing the expectable
      "unloading effect" following valgus high tibial osteotomy.
AB  - PURPOSE: The purpose of this study was to evaluate whether the expectable
      postoperative pain relief following valgus high tibial osteotomy (HTO) is
      reliably predictable with the temporary use of an unloading knee brace
      preoperatively. METHODS: Fifty-seven patients with symptomatic varus malalignment
      were treated with a valgus producing unloading knee brace for 6-8 weeks. The pain
      intensity in the respective knee compartment was monitored using the visual
      analogue scale (VAS) before and following this treatment. A "positive" Brace-Test
      was defined as a pain relief medially without initiated symptoms laterally. In
      these cases, a valgus HTO was suggested as a promising surgical option. Patients
      who were subsequently operated were clinically re-evaluated 1 year
      postoperatively to compare the postoperative outcome with the result of the Brace
      Test. RESULTS: The mean VAS score decreased from 6.7 [standard deviation (SD)
      1.6] to 2.5 points (SD 1.7) (p < 0.001) following the Brace-Test. Overall, 48
      patients had a positive test. A valgus HTO was performed in 29 of them. The mean
      postoperative VAS score was 1.9 (SD 1.7) points with no difference to the result
      of the test (n.s.). Nineteen patients with a positive test initially decided for
      a conservative treatment. In three of nine patients with a negative test, a total
      knee replacement was performed. CONCLUSION: This study shows that the temporary
      use of an unloading valgus producing knee brace may well predict future outcome
      of HTO surgery in terms of expectable postoperative pain relief. The Brace-Test
      gives both the patient and the orthopaedic surgeon more detailed preoperative
      information, especially in critical or borderline indications. Thus, it is a
      useful tool to test the unloading effect before indicating an HTO. LEVEL OF
      EVIDENCE: III.

PMID- 24435222
TI  - Mobile-bearing prosthesis and intraoperative gap balancing are not predictors of
      superior knee flexion: a prospective randomized study.
AB  - PURPOSE: Range of motion is a crucial measure of the outcome of total knee
      arthroplasty. Gap balancing technique and mobile-bearing prosthesis can improve
      postoperative range of motion. The purpose of this study was to determine the
      factors that are predictive of the postoperative range of motion. METHODS: A
      total of 94 knees with varus osteoarthritis were prospectively randomized to
      receive either a posterior-stabilized mobile-bearing or a posterior-stabilized
      fixed-bearing prosthesis. All preoperative and postoperative protocols and
      operative techniques were identical in the two groups. Extension and flexion
      joint gaps were measured using a tensor device during the operation. Multiple
      regression analysis was conducted to determine the best predictors of the knee
      flexion angle 2 years after the operation. The independent variables were type of
      prosthesis (mobile-bearing or fixed-bearing), difference between flexion and
      extension joint gaps (mm), age, gender, body mass index (BMI), preoperative and
      intraoperative knee flexion angles, change in posterior condylar offset, and
      posterior tilt of the tibial plateau. RESULTS: The mean difference between
      flexion and extension joint gaps was 0.8 +/- 1.3 (mean +/- SD) mm for mobile
      bearing and 0.8 +/- 1.9 mm for fixed-bearing prosthesis. The mean flexion angle
      for mobile-bearing and fixed-bearing groups was 120 +/- 16 degrees  and 116 +/-
      20 degrees  preoperatively (n.s.), 142 +/- 9 degrees  and 141 +/- 12 degrees 
      intraoperatively (n.s.), and 129 +/- 10 degrees  and 128 +/- 13 degrees  at 2
      years postoperatively (p = 0.773), respectively. Predictors were identified in
      the following three categories: (1) preoperative flexion angle, (2)
      intraoperative radiographic flexion angle, and (3) BMI (R = 0.603, p < 0.001).
      CONCLUSIONS: Mobile-bearing prosthesis and optimal gap balancing did not result
      in superior postoperative flexion angle. Better preoperative and intraoperative
      flexion angles and lower BMI were the significant predictors for better
      postoperative flexion angle. LEVEL OF EVIDENCE: Therapeutic study, Level I.

PMID- 24435223
TI  - Improved positioning of the tibial component in unicompartmental knee
      arthroplasty with patient-specific cutting blocks.
AB  - PURPOSE: Unicompartmental knee arthroplasty (UKA) has recently regained
      popularity for the treatment of osteoarthritis of the knee. Numerous authors have
      cited alignment as an important prognostic factor in the survival of UKA. Limb
      alignment affects not only the longevity of UKA by influencing wear of
      polyethylene, but also affects the unreplaced contralateral compartment.
      Malpositioning of the components may result in unequal wear patterns, thus
      further leading to early failure and additionally influencing clinical outcome as
      well. However, there is a lack of techniques to assure a high accuracy of the
      implant positioning. METHODS: In this study, we investigated tibia component
      alignment of 28 medial UKAs implanted with patient-specific cutting blocks. Three
      patients were excluded due to bad imaging. Measurements of tibial component
      alignment from postoperatively computed tomography (CT) scans were compared to
      respective CT-based preoperative plannings to assess the accuracy of implant
      positioning. RESULTS: Our results show excellent high accuracy of tibial implant
      position in tibial varus/valgus (Delta 0.3 degrees  +/- 1.7 degrees ), posterior
      slope (Delta 1.1 degrees  +/- 2.6 degrees ) and external rotation (Delta 1.5
      degrees  +/- 3.3 degrees ). CONCLUSION: We conclude that patient-specific cutting
      blocks improve the accuracy of tibia component positioning in unicompartmental
      knee arthroplasty. LEVEL OF EVIDENCE: Case series with no comparison group, Level
      IV.

PMID- 24435224
TI  - A one-pot septanoside formation and glycosylation of acyclic dithioacetals
      derived from 1,2-cyclopropanated sugars.
AB  - Ring opening of 3-oxo-1,2-cyclopropanated sugars with thiols leads to the
      serendipitous discovery of the synthesis of sugar based homologated acyclic
      dithioacetals. These acyclic dithioacetals were found to undergo one-pot
      septanoside formation followed by stereoselective glycosylation in the presence
      of glycosyl acceptors under glycosylation reaction conditions. 

PMID- 24435225
TI  - Application of physiologically based absorption modeling to formulation
      development of a low solubility, low permeability weak base: mechanistic
      investigation of food effect.
AB  - Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to
      facilitate drug development, hereby we developed a PBPK model to systematically
      investigate the underlying mechanisms of the observed positive food effect of
      compound X (cpd X) and to strategically explore the feasible approaches to
      mitigate the food effect. Cpd X is a weak base with pH-dependent solubility; the
      compound displays significant and dose-dependent food effect in humans, leading
      to a nonadherence of drug administration. A GastroPlus Opt logD Model was
      selected for pharmacokinetic simulation under both fasted and fed conditions,
      where the biopharmaceutic parameters (e.g., solubility and permeability) for cpd
      X were determined in vitro, and human pharmacokinetic disposition properties were
      predicted from preclinical data and then optimized with clinical pharmacokinetic
      data. A parameter sensitivity analysis was performed to evaluate the effect of
      particle size on the cpd X absorption. A PBPK model was successfully developed
      for cpd X; its pharmacokinetic parameters (e.g., C max, AUCinf, and t max)
      predicted at different oral doses were within +/-25% of the observed mean values.
      The in vivo solubility (in duodenum) and mean precipitation time under fed
      conditions were estimated to be 7.4- and 3.4-fold higher than those under fasted
      conditions, respectively. The PBPK modeling analysis provided a reasonable
      explanation for the underlying mechanism for the observed positive food effect of
      the cpd X in humans. Oral absorption of the cpd X can be increased by reducing
      the particle size (<100 nm) of an active pharmaceutical ingredient under fasted
      conditions and therefore, reduce the cpd X food effect correspondingly. 

PMID- 24435227
TI  - Convergent Validity of the Strength-Based Behavioral and Emotional Rating Scale
      with Youth in a Residential Setting.
AB  - Strength-based assessment has been identified as an appropriate approach to use
      in planning treatment and evaluating outcomes of youth in residential settings.
      In previous research, the Behavioral and Emotional Rating Scale-2, a standardized
      and norm-referenced strength-based measure, has demonstrated adequate reliability
      and validity with youth served in community and educational settings. The purpose
      of the present study was to examine the internal reliability and convergent
      validity of the BERS-2 by comparing the test to the Child Behavior Checklist and
      the Symptoms and Functioning Severity Scale. The results indicate that the scores
      from the BERS-2 are internally consistent and converge with other behavioral and
      emotional measures which, taken together, suggest that the BERS-2 could be
      acceptable for assessing the emotional and behavioral strengths of youth in
      residential settings. Study limitations and future research directions are
      identified. 

PMID- 24435228
TI  - Microbodies and glyoxylate-cycle enzyme activities in filamentous fungi.
AB  - Microbodies were observed in the hyphal tips of all 14 fungi investigated. Their
      morphology varied among the fungi and their numbers were influenced by the growth
      medium. Microbodies were closely associated with mitochondria in one fungus and
      with the endoplasmic reticulum in several fungi. Catalase was not detected in
      microbodies with the diaminobenzidine cytochemical procedure even though catalase
      activity was present in extracts of these fungi. The activities of the glyoxylate
      cycle enzymes isocitrate lyase and malate synthase were affected by the growth
      medium and were particulate in the two fungi studied by differential
      centrifugation. Microbodies are abundant, and they are ubiquitous among the fungi
      and in some cases they may contain glyoxylate-cycle enzymes. 

PMID- 24435226
TI  - Correlates of treatment engagement in an ADHD primary care-based intervention for
      urban families.

PMID- 24435229
TI  - The effect of osmotic stress on the oxidation of glycolate by the blue-green alga
      Anacystis nidulans.
AB  - Anacystis nidulans Richt. was shown to assimilate glycolic acid, and uptake was
      light-stimulated. In the dark 90% of the glycolate taken up was oxidised to CO2.
      Both light and dark uptake was completely inhibited by alpha-hydroxysulphonates
      but was unaffected by isonicotinyl hydrazide. 3-(3,4-Dichlorophenyl)-1,1-dimethyl
      urea (DCMU) reduced the rate of light uptake but not to the uptake level of the
      dark control. Subjecting the algal cells to osmotic stress by incubation in 0.6 M
      mannitol for 1 h, which reduces the photosynthetic activity of this alga, causes
      an 80% reduction in both light and dark glycolate uptake although the uptake of
      glyoxylate, formate, acetate, and glycine is not markedly affected. Osmotic
      stress had no effect on the uptake and metabolism of glycolate by Anabaena flos
      aquae (Lyngbye) Bred. and Oscillatoria sp. The activity of glycolate
      dehydrogenase in Anacystis was also reduced by osmotic shock while the activity
      of other enzymes was unaffected. 

PMID- 24435230
TI  - Dark starvation and plant metabolism : II. CO2 fixation in isolated chloroplasts.
AB  - The fixation pattern of radioactive labelled photosynthetic intermediates was
      followed under steady state conditions during prolonged dark starvation of
      spinach plants (Spinacia oleracea L.). It is suggested that the considerable
      increase of radioactive dihydroxyacetonephosphate is correlated with a specific
      leakage of the outer chloroplast envelope induced by dark starvation. The primary
      fixation product, phosphoglyceric acid, followed the same decreasing tendency as
      observed for the net CO2 fixation. In contrast, the relative label in other
      intermediates is the same as in the controls. When after several days of dark
      starvation the plants were again transferred into light, a regeneration of the
      CO2 fixation accompanied by the appearance of a normal fixation pattern was
      observed. Since the regeneration was prevented by the addition of lincomycin, the
      net increase is considered to be due to a new protein synthesis rather than a
      reactivation. 

PMID- 24435231
TI  - Dark starvation and plant metabolism : III. CO2 fixation and the distribution of
      radioactive intermediates in leaf discs from spinach plants.
AB  - When leaf discs from spinach plants (Spinacia oleracea L.) maintained in the dark
      for several days were subsequently illuminated, the decrease of incorporated
      (14)CO2 measured under steady state conditions was found to be accompanied by an
      altered fixation pattern. Substances found to contain a significantly lower
      label, were malate and aspartate. In contrast, an enhanced incorporation of
      radioactivity was observed for those substances known to be formed during light
      respiration. Since the same tendencies were obtained at higher CO2 concentrations
      and after the removal of the lower epidermis, a new metabolic situation rather
      than an impaired CO2 supply, was considered to be responsible for the altered
      turnover of intermediates. The constant ratio in the labelling of intermediates
      formed in the chloroplasts and the known localization of enzymes involved in the
      formation of C-4 components led us to conclude that primarily the activity of
      cytoplasmic enzymes is influenced by dark. 

PMID- 24435232
TI  - Metabolic regulation in C4 photosynthesis: Phosphoenol pyruvate carboxylase and
      3C intermediates of the photosynthetic carbon reduction cycle.
AB  - The effects of 3C intermediates of the photosynthetic carbon reduction (PCR)
      cycle (glyceraldehyde 3 phosphate [G3P], dihydroxyacetone phosphate and 3
      phosphoglyceric acid) on the activity of phosphoenol pyruvate (PEP) carboxylase
      from Pennisetum purpureum (a C4 plant) have been investigated. Addition of these
      compounds, at concentrations greater than about 3 mM, to standard assay mixtures
      (5 mM concentrations of PEP, HCO3 (-) and Mg(2+)) reduced the observed activity.
      The extent of inhibition was greater at lower (<5 mM) concentration of Mg(2+).
      G3P was the most potent inhibitor. During studies of saturation kinetics with PEP
      as variable substrate it was found that addition of these 3C compounds (2mM)
      reduced the sigmoid nature of Michaelis-Menten plots and reduced the value of n
      obtained from Hill plots from about 3 to near one. The results are disussed in
      terms of the possible regulation of C4 photosynthesis by intermediates of the PCR
      cycle which are easily leaked from chloroplasts. 

PMID- 24435233
TI  - Condensed phosphates in Lemna minor L. and their relationship to nucleic acids.
AB  - After previous incubation in a P-free culture medium whole plants of Lemna minor
      L. were given [(32)P]-orthophosphate in the logarithmic and in the stationary
      growth phase. The condensed phosphates could be separated from the nucleic acids
      by fractionation on methylated serum albumin and Kieselgur (MAK). The various
      inorganic condensed phosphates were eluted before the nucleic acids. The former
      were dialyzed and separated by two-dimensional thin layer chromatography on a
      mixture of cellulose and microcrystalline cellulose using an acid and an alkaline
      solvent in succession. (32)P-radioactivity was present in all linear
      oligophosphates containing 2 to 7 residues, in cyclic metaphosphates (tri-, tetra
      , penta- and hexametaphosphates) and in high-molecular condensed phosphates which
      remained at the starting point.Among the low-molecular inorganic oligophosphates
      the trimetaphosphate contained significantly more radioactivity than the other
      compounds. The labeling rate of (32)P-incorporation depended on the previous
      depletion of phosphate. In the logarithmic phase maximal labeling occurred after
      4 h following a 10 h period of phosphate depletion; in the stationary phase the
      maximum rate was reached 5 h after the end of a 4.5 h period of phosphate
      depletion. The results indicate that the phosphate pool was restored first and
      that the nucleic acids were labeled subsequently. That is to say: in contrast to
      previous findings by other authors, our results show that net synthesis of
      inorganic condensed phosphates does takes place during the logarithmic
      phase.After cultivation of Lemna for 24 h or longer in a P-free medium the DNA
      incorporated more (32)P than the other nucleic acids during the logarithmic
      phase. During the stationary phase [(32)P]-orthophosphate incorporation into
      nucleic acids was markedly lower than during the logarithmic phase. 

PMID- 24435234
TI  - Correlative effects of fruits and leaves in senescence of pea plants.
AB  - Whole plant senescence was studied in peas (Pisum sativum L.) by defruiting,
      defoliating, and grafting. Fruit removal delays senescence. The delay in
      senescence is associated with the initiation of bud expansion at nodes near those
      producing pods. The apical meristem dies regardless of defruiting though later
      than normal phants.Graft unions are only made if the stock is defruited The
      pattern of senescence of unions indicates a non polar movement of senescence
      factors from fruits.Leaves seem not to be involved in whole plant senescence. 

PMID- 24435235
TI  - The movement of 2,4-dichlorophenoxy acetic acid in root segments of Pisum sativum
      L.
AB  - The movement of 2,4-Dichlorophenoxy acetic acid (2,4-D) through subapical
      segments of the primary roots of Pisum seedlings has been investigated using [1
      (14)C]2,4-D.Donation of [1-(14)C]2,4-D to the apical or basal ends of Pisum root
      segments at 25 degrees C in darkness revealed a preferential movement of the
      compound towards the root apex i.e. an acropetal polarisation. Thus the movement
      of [1-(14)C]2,4-D into receiver blocks applied to the apical ends of the segments
      is greater than that into receiver blocks applied to the basal ends of the
      segments The low level of basipetal transport appears to be associated with a
      restriction of the movement of [1-(14)C]2,4-D to the half of the segment nearest
      the donor block.Acropetal transport of 2,4-D is faster than basipetal transport
      in root segments maintained at 15 degrees  and 35 degrees  C but is slower than
      basipetal transport if the segments are maintained at 25 degrees C. Maximum
      velocitees are 0.71 and 0.83 mm h(-1) for acropetal and basipetal transport
      respectively.Evidence from experiments carried out (a) in an anaerobic
      environment in the presence or absence of sodium fluoride and (b) over a range of
      temperatures from 1-35 degrees C, indicates that the movement of [1-(14)C]2,4-D
      is dependent on the metabolic activity of the Pisum root segments.Release of
      (14)CO2 during transport of [1-(14)C]2,4-D is small and supports chromatographic
      evidence that negligible degradation of the 2,4-D molecules takes place during
      transport through the root segments. 

PMID- 24435236
TI  - A method for estimating the proportion of sieve tubes in the phloem of higher
      plants.
AB  - A statistical method has been developed for the estimation of the proportion of
      phloem area occupied by sieve tube lumen which is applicable to most higher
      plants. By simple probability, the number of sieve tubes in a given area of
      phloem is equal to the number of sieve plates present in a series of transverse
      sections whose total thickness equals the mean sieve element length. The case of
      oblique sieve plates, where the plate is divided and occurs in more than one
      section, has also been dealt with and a solution obtained. Estimates of the
      proportion of phloem area occupied by sieve tubes have been made by this method
      in willow (Salix viminalis L.), sugar beet (Beta vulgaris L.) and a cucurbit
      (Ecballium elaterium L.) and the values obtained discussed in relation to
      estimates made previously by other methods. 

PMID- 24435237
TI  - An effect of ethylene on the endoplasmic reticulum of expanding cells of
      etiolated shoots of Pisum sativum L.
AB  - Within 6 h of supplying ethylene to intact etiolated seedlings of Pisum sativum
      L. increasingly long profiles of rough and smooth endoplasmic reticulum (ER)
      appear in sections of epidermal and cortical cells from the hook region. By 24 h
      some profiles exceed 10 MUm in length, more than 10 times the length of the
      longest commonly observed in control tissue. These profiles are not artifacts of
      the different preparations, for similar extended profiles occur in sections of
      pellets of rough ER which have been prepared from subapical internodes of treated
      seedlings by extraction and separation of the membranes on sucrose gradients. It
      is proposed that the changes in rough ER result from a 'stabilisation' of the
      membranes brought about by a reduced rate of phospholipid turnover in the
      presence of ethylene. 

PMID- 24435238
TI  - A quantitative analysis of cytokinin using single-ion-current-monitoring.
AB  - The levels of the cytokinin 6-(o-hydroxybenzylamino)-9-beta-D-ribofuranosylpurine
      (o-OH BAP riboside) have been measured in attached leaves of poplar (Populus x
      robusta Schneid) using the technique of single-ion current monitoring (SICM). The
      use of 6-(p-hydroxybenzylamino)-9-beta-D-ribofuranosylpurine (p-OH BAP riboside)
      as an internal standard has enabled quantitative measurements of recovery to be
      made. 

PMID- 24435239
TI  - On the mechanism of light induction of plant microsomal cinnamic acid 4
      hydroxylase.
AB  - The specific activities of the enzymes cinnamic acid 4-hydroxylase and cytidine
      5'-diphospho-choline: 1,2-diacylglycerol cholinephosphotransferase (E.C. 2.7.8.2)
      were determined in microsomal fractions from a) dark-grown and b) irradiated
      parsley (Petroselinum hortense Hoffm.) cell suspension cultures. Cinnamic acid 4
      hydroxylase activity was increased 4-fold after light treatment, while
      cholinephosphotransferase activity was decreased by about one third of its
      original activity. It can be concluded that increased microsomal lecithin
      biosynthesis is not required for the light-induced increase of cinnamic acid 4
      hydroxylase activity, although the latter enzyme has previously been found to
      require a lipid cofactor for activity. 

PMID- 24435240
TI  - Stimulation of precursor rRNA synthesis in the cotyledons of mustard seedlings by
      phytochrome.
AB  - Cotyledons of mustard (Sinapis alba L.) seedlings irradiated with far-red light
      were shown to synthesize high molecular weight precursor rRNA (2.4*10(6)
      2.9*10(6) dalton) at a considerably enhanced rate compared to dark-grown
      cotyledons. This result was obtained by pulse-labelling cotyledons isolated from
      48 h old seedlings (which were either irradiated for 12 h with standard far-red
      light before dissection, or kept in darkness) with [(3)H]uridine for 15 min. The
      data verify the conclusion that phytochrome is able to activate the transcription
      of rRNA cistrons. 

PMID- 24435242
TI  - Split spinal cord malformation: report of 5 cases in a single Chinese center and
      review of the literature.
AB  - BACKGROUND: Split spinal cord malformation (SSCM) is rare in scoliosis. This
      study evaluated the safety and effectiveness of one-stage surgical treatment of
      congenital scoliosis (CS) in patients with SSCM in a single Chinese center.
      METHOD: A retrospective study of 5 cases who underwent surgery for CS with SSCM
      (2 type I and 3 type II) from March 2004 to March 2012. Patients included 4
      females and 1 male with a mean age of 13.8 years. All patients underwent one
      stage posterior fusion surgery with resection of a bony spur firstly in SSCM type
      I, but we did nothing to the SSCM in type II. Clinical symptoms and radiological
      changes were evaluated preoperatively and for at least 2 years postoperatively.
      RESULTS: Preoperatively, 5 patients had variant neurological and other symptoms.
      They had a mean preoperative Cobb angle of 63 +/- 20 degrees  and T5-T12 kyphosis
      of 30 +/- 21 degrees . The mean postoperative Cobb angle was 30.2 +/- 19.8
      degrees  with a correction rate of 57.2 +/- 17.0%. At the 3-month follow-up the
      Cobb angle loss was 3.0 +/- 6.8 degrees , and at the 2-year follow-up the Cobb
      angle loss was 6.5 +/- 9.7 degrees . Hyperkyphosis was significantly corrected
      after surgery but correction loss was indicated at the 2-year follow-up (p <
      0.01). There were no neurological deficit complications or deteriorated
      neurological signs postoperatively or at follow-up. CONCLUSIONS: One-stage
      surgical treatment of CS with SSCM could be safe and effective, but we need
      further multicenter studies with larger samples. Intraspinal intervention of bone
      spur was recommended in SSCM type I before deformity correction, while in SSCM
      type II it was needless.

PMID- 24435243
TI  - Observational cross-sectional study of compliance with the fast track protocol in
      elective surgery for colon cancer in Spain.
AB  - PURPOSE: The purpose of this study was to establish the degree of compliance with
      the fast track (enhanced recovery) protocol in habitual clinical practice and to
      determine which measures are fundamental for achieving the results obtained by
      applying the entire protocol. METHODS: Observational, cross-sectional,
      multicenter trial was conducted. Participating hospitals prospectively recorded
      data from at least ten consecutive patients undergoing surgery for colon cancer
      who were applied some or all of the items comprising the enhanced recovery
      protocol. The data were analyzed both globally and dividing the sample into the
      two groups of patients. RESULTS: Data on 363 patients from 25 hospitals were
      recorded, one hundred seventy-three in the "non-fast track" group and 190 in the
      "fast track" group. The non-fast track group complied with a mean of 5.4 (+/-1.8)
      items and the fast track group with a mean of 8.4 (+/-1.8) items. The mean
      functional hospital stay was 7.3 (+/-5.1) days in the non-fast track group and
      6.2 (+/-5.1) days in the fast track group (p < 0.05). Morbidity was 31.1 % in the
      fast track group and 24.3 % in the non-fast track group, though the differences
      were not statistically significant. The only prognostic factors that have an
      impact on improving the results are measures against hypothermia and mobilization
      before 24 h. CONCLUSION: Compliance with the enhanced recovery protocol is not
      exhaustive in habitual clinical practice. However, greater compliance was
      associated with shorter hospital stay without any increase in morbidity. The only
      items clearly associated with reduced functional hospital stay were measures
      against hypothermia and mobilization before 24 h.

PMID- 24435244
TI  - Pilot double-blinded study to assess efficacy and tolerability of morphine
      sulphate oral solution (Oramorph(r)) given preoperatively as add-on therapy
      within a multimodal postoperative pain approach in patients undergoing
      laparoscopic cholecystectomy.
AB  - BACKGROUND: This study aims at investigating the effect of a single pre-operative
      oral administration of morphine sulphate (Oramorph(r)) on pain after laparoscopic
      cholecystectomy (LC). METHODS: Forty-one ASA I-III patients, aged 18-65 years,
      undergoing LC were randomly, double-blindly allocated to treatment (N.=20, 30mg
      Oramorph(r), group M) or placebo (N.=21, group P). General anesthesia was
      maintained with propofol and remifentanil. All patients received ketamine 0.2
      mg/kg iv at induction, intraoperative ketorolac 30mg iv and tramadol
      postoperatively (iv PCA: bolus 50 mg, lock-out 30 min, max 100 mg/4 hours).
      Numerical rating scale for pain (NRS), White's fast track and PADSS scores,
      tramadol consumption and adverse events were recorded for the first 24h. All
      patients underwent State Trait Anxiety Inventory (STAI) and Mini Mental State
      Examination (MMSE). RESULTS: Anthropometric characteristics, MMSE, STAI, ASA
      status, NRS rest, White's and PADDS scores, PONV incidence were similar. Group M
      showed significantly lower NRS on movement during the first 3 hours after
      awakening. Cumulative tramadol consumption was lower in group M than in group P
      (185+/-142 mg versus 263+/-199 mg, P=0.199). CONCLUSION: Within a multimodal
      approach, a single preoperative oral administration of 30 mg of morphine sulphate
      in patients undergoing LC did not improve pain at rest, but improved NRS on
      movement during the first 3 hours after awakening. Group P required a higher mean
      dose of tramadol compared to Group M, although not significantly. The safety
      profile of Oramorph(r) allowed fast extubation and awakening times as well as
      prompt home discharge within 6 hours from surgery.

PMID- 24435245
TI  - Supramolecular reactivity in the gas phase: investigating the intrinsic
      properties of non-covalent complexes.
AB  - The high vacuum inside a mass spectrometer offers unique conditions to broaden
      our view on the reactivity of supramolecules. Because dynamic exchange processes
      between complexes are efficiently suppressed, the intrinsic and intramolecular
      reactivity of the complexes of interest is observed. Besides this, the
      significantly higher strength of non-covalent interactions in the absence of
      competing solvent allows processes to occur that are unable to compete in
      solution. The present review highlights a series of examples illustrating
      different aspects of supramolecular gas-phase reactivity ranging from the
      dissociation and formation of covalent bonds in non-covalent complexes through
      the reactivity in the restricted inner phase of container molecules and step-by
      step mechanistic studies of organocatalytic reaction cycles to cage contraction
      reactions, processes induced by electron capture, and finally dynamic molecular
      motion within non-covalent complexes as unravelled by hydrogen-deuterium exchange
      processes performed in the gas phase. 

PMID- 24435246
TI  - Developmental trajectory of contextual learning and 24-h acetylcholine release in
      the hippocampus.
AB  - To determine the developmental trajectory of hippocampal function in rats, we
      examined 24-h changes in extracellular acetylcholine (ACh) levels and contextual
      learning performance. Extracellular ACh significantly correlated with spontaneous
      behavior, exhibiting a 24-h rhythm in juvenile (4-week-old), pubertal (6-week
      old), and adult (9- to 12-week-old) rats. Although juveniles of both sexes
      exhibited low ACh levels, adult males had higher ACh levels than adult females.
      Moreover, juveniles exhibited much more spontaneous activity than adults when
      they showed equivalent ACh levels. Similarly, juveniles of both sexes exhibited
      relatively low contextual learning performance. Because contextual learning
      performance was significantly increased only in males, adult males exhibited
      better performance than adult females. We also observed a developmental
      relationship between contextual learning and ACh levels. Scopolamine pretreatment
      blocked contextual learning and interrupted the correlation. Since long-term
      scopolamine treatment after weaning impaired contextual learning in juveniles,
      the cholinergic input may participate in the development of hippocampus. 

PMID- 24435247
TI  - Genitourinary symptoms and their effects on quality of life in women with uterine
      myomas.
AB  - INTRODUCTION AND HYPOTHESIS: This study was designed to determine the presence of
      genitourinary symptoms and their effects on quality of life (QOL) in women with
      uterine myomas. METHODS: A total of 145 women with ultrasonography (US) diagnosis
      of anterior myoma were divided into two groups according to myoma size: (1) those
      <=5 cm (n = 75), and (2) those >5 cm (n = 70). The control group comprised
      previously matched 94 women with a normal-appearing uterus on US. Study
      participants answered the Urogenital Distress Inventory (UDI-6) and the
      Incontinence Impact Questionnaire (IIQ-7). Pelvic examination was performed, and
      urinary symptoms were recorded. The chi-square test and Fischer's exact test were
      used to compare qualitative data. The Kruskal-Wallis test and Dunn's test were
      used to compare groups. Statistical significance was set at P <0.05. RESULTS: The
      frequency of genitourinary symptoms was significantly higher in women with
      myomas, including stress urinary incontinence (SUI), urgency, frequency, urge
      urinary incontinence (UUI), and dyspareunia. SUI and mixed urinary incontinence
      (MUI) were the most common symptoms associated with myoma size. Total UDI-6
      scores were significantly higher in women with myomas than in control patients (P
      < 0.0001). UDI scores associated with UI and obstructive symptoms were higher in
      women with myomas >5 cm than in other women. IIQ scores regarding physical
      activity, travel, and emotional health were significantly higher in women with
      myomas >5 cm than in other women (P < 0.001). CONCLUSIONS: Urinary tract
      dysfunction is associated with anterior myomas, increasing in association with
      myoma size, and significantly affects QOL.

PMID- 24435248
TI  - A randomised controlled trial of abdominal versus laparoscopic sacrocolpopexy for
      the treatment of post-hysterectomy vaginal vault prolapse: LAS study. Reply to
      comment.

PMID- 24435249
TI  - A randomised controlled trial of abdominal versus laparoscopic sacrocolpopexy for
      the treatment of post-hysterectomy vaginal vault prolapse: LAS study. Comment.

PMID- 24435251
TI  - Investigating design principles of micropatterned encapsulation systems
      containing high-density microtissue arrays.
AB  - Immunoisolation is an important strategy to protect transplanted cells from
      rejection by the host immune system. Recently, microfabrication techniques have
      been used to create hydrogel membranes to encapsulate microtissue in an arrayed
      organization. The method illustrates a new macroencapsulation paradigm that may
      allow transplantation of a large number of cells with microscale spatial control,
      while maintaining an encapsulation device that is easily maneuverable and
      remaining integrated following transplantation. This study aims to investigate
      the design principles that relate to the translational application of
      micropatterned encapsulation membranes, namely, the control over the
      transplantation density/quantity of arrayed microtissues and the fidelity of pre
      formed microtissues to micropatterns. Agarose hydrogel membranes with microwell
      patterns were used as a model encapsulation system to exemplify these principles.
      Our results show that high-density micropatterns can be generated in hydrogel
      membranes, which can potentially maximize the percentage volume of cellular
      content and thereby the transplantation efficiency of the encapsulation device.
      Direct seeding of microtissues demonstrates that microwell structures can
      efficiently position and organize pre-formed microtissues, suggesting the
      capability of micropatterned devices for manipulation of cellular transplants at
      multicellular or tissue levels. Detailed theoretical analysis was performed to
      provide insights into the relationship between micropatterns and the
      transplantation capacity of membrane-based encapsulation. Our study lays the
      ground for developing new macroencapsulation systems with microscale
      cellular/tissue patterns for regenerative transplantation. 

PMID- 24435250
TI  - Rate and predictors of postpartum depression in a 22-year follow-up of a cohort
      of earthquake survivors in Armenia.
AB  - Disasters have serious long-term impact on mental health for those exposed. The
      aim of this study was to identify predictors of postpartum depression among
      survivors of the 1988 devastating earthquake in Armenia. A nested case-control
      design was applied to investigate postpartum depression in a large-scale cohort
      of survivors followed between 1990 and 2012. From an original group of 725 adults
      who were assessed for psychopathology in 1990, 146 women reported having a
      delivery after the earthquake and were included in this study. Women with
      postpartum depression were identified using Edinburgh Postnatal Depression Scale.
      A logistic regression model was fitted to identify the predictors of postpartum
      depression. Of the 146 women, 19 (13.0%) had postpartum depression. Five
      independent predictors of postpartum depression were identified: number of
      woman's stressful life events (odds ratio (OR)=2.06), her prior history of
      postpartum depression (OR=16.98), delivering sick/dead neonate (OR=13.65), poor
      living standards during the post-earthquake decade (OR=5.77), and perceiving
      oneself reliable in 1990 (OR=0.24). Anxiety in 1990 was marginally significantly
      related to the outcome (OR=3.75). The rate of postpartum depression in this 22
      year cohort was similar to that among the Armenian general population. Earthquake
      exposure was not related to postpartum depression, indicating that the impact of
      disaster-related trauma diminishes over time. The identified predictors provided
      evidence to develop interventions targeting groups of women most prone to
      postpartum depression under such circumstances.

PMID- 24435256
TI  - An unusual case of chronic otorrhea.

PMID- 24435257
TI  - A child with pneumomediastinum.

PMID- 24435258
TI  - Vertigo and sudden hearing loss at 35,000 feet.

PMID- 24435259
TI  - Nickel-catalyzed triarylamine synthesis: synthetic and mechanistic aspects.
AB  - An improved protocol was described for the amination of chloroarenes with
      diarylamines under NiCl2(PCy3)2 catalysis in the presence of a Grignard reagent
      as base. This method fully suits bromo-/iodoarene substrates as well, and even is
      expanded to certain aryl tosylates. A preliminary investigation into the
      mechanism suggests that this amination reaction might proceed through Ni(I) and
      Ni(III) intermediates rather than via the usually expected Ni(0)-Ni(II) cycle. 

PMID- 24435260
TI  - [Endogenous variations of productivity in Scenedesmus acutus and their relation
      to the nucleic acid metabolism].
AB  - 1. In Scenedesmus acutus Tomaselli, endogenous variations in cell progeny
      production and chlorophyll formation have been found which are very similar to
      those previously described in Chlorella by Hesse (Z. Pflanzenphysiol. 67, 58-77,
      1972). When the dark phase of the light-dark-cycle is prolonged to a certain
      extent, cell productivity drops to a minimal value during the next normal light
      dark-cycle. If the duration of the supplementary dark treatment comes near to 24
      h, cell productivity is almost normal during the next cycle. 2. Nucleic acid
      labeling with radioactive precursors is very similar in Scenedesmus acutus and
      Chlorella pyrenoidosa. Short time labeling with uridine results in labeled
      chloroplastic RNA and DNA, the cytoplasmic RNA being almost unlabeled. With
      guanosine, both chloroplastic and cytoplasmic RNA as well as DNA are labelled. In
      nucleic acid separation on acrylamide gels special caution must be taken, since
      endocellular RNases are particularely active in some cell stages of Scenedesmus.
      Optimal results are obtained with ripe mother cells; during nucleic acid
      purification, cell homogenates have to be frozen together with the phenol-cresol
      mixture. 3. Large differences in guanosine incorporation are found after
      treatment of the cells with supplementary dark time. After the normal 10:12 h
      light-dark-cycle, and also after 24 h of supplementarry dark time, much more
      radioactive guanosine is incorporated into chloroplastic RNA than into
      cytoplasmic RNA. After 12 h of supplementary dark time, however, cytoplasmic RNA
      is more extensively labeled than chloroplastic RNA. 4. When the specific
      radioactivity of guanosine is diluted to one half, the incorporation into the
      rRNA of cytoplasm and chloroplast is strongly reduced. This is due to the filling
      up of the guanosine pool in the two compartments. In contrast, DNA labeling is
      hardly influenced by reduced specific radioactivity of the precursor. This may be
      interpreted as meaning that the radioactive labeling reflects the rate of DNA
      synthesis rather than the size of the guanosine pool in the nucleus. Differences
      found in the labeling of DNA after 12 and 24 h of supplementary dark time can
      than be interpreted as variations in DNA synthesis rate. 

PMID- 24435261
TI  - Microbodies and an anomalous "microcylinder" in the ultrastructure of plants with
      Crassulacean acid metabolism.
AB  - An ultrastructural study was made of the leaf tissues of four species of plants
      in three genera with Crassulacean acid metabolism ("CAM" plants): Kalanchoe
      daigremontiana Hamet et Perrier, K. verticillata Elliot, Sedum rubrotinctum
      clausen and Crassula tetragona L. Microbodies similar in appearance, with
      fibrillar or granular nucleoids but no crystalline deposits, were present in the
      mesophyll of all four species. The microbodies resembled in size and abundance
      those of C3 plants more closely than those of C4 plants, both under long-day and
      short-day conditions. The reaction for catalase activity employing 3,3'
      diaminobenzidine produced a heavy deposit in the microbodies; the reaction was
      blocked by the catalase inhibitor, aminotriazole.Some of the plants of the two
      species of Kalanchoe studied contain in the epidermal and mesophyll cells of the
      leaves and plantlets an organelle-like structure consisting of a hollow cylinder,
      90-160 nm in diameter and up to 2 MUm or more in length, around which 18-20 or
      more minute tubules are wound in a steep helix. The tubules are only ca. 9 nm in
      diameter, hence are much smaller than conventional microtubules. The cylinder and
      surrounding tubules, herein tentatively assigned the term "microcylinder" for
      convenience, may represent a product of viral infection, or may be an organelle
      that appears at certain stages of growth or under particular environmental
      conditions. In any case it may prove to be of considerable importance for
      investigators of CAM plant physiology. 

PMID- 24435262
TI  - [Low energy photocontrol of amaranthin formation in seedlings of Amarantus
      tricolor L. var. bicolor ruber Hort].
AB  - A grating monochromator has been used to study the effect of narrow wave-bands (5
      nm) at a low energy level between 420 and 800 nm on the biosynthesis of
      amaranthin in Amarantus tricolor L. var. bicolor ruber Hort. seedlings. Besides a
      sharp peak in the red with a maximum at 660 nm, a narrow zone of activity in the
      blue has been detected (max. 440 nm).When seedlings cultivated on different
      substrates were sequentially exposed either to red (660 nm) and far red or to
      blue (440 nm) and far red, the second treatment, i.e. far red (730 or 735 nm),
      annihilated the effect of the first one, without having any influence on the
      chemical inductive treatments (kinetin or dihydroxy-3,4-phenylalanine). 

PMID- 24435263
TI  - [Light-mediated de-novo synthesis of delta-aminolaevulinate dehydratase in
      isolated Avena etioplasts].
AB  - A light dependent increase of the activity of delta-aminolaevulinate dehydratase
      (E.C. 4.2.1.24) in isolated etioplasts of Avena sativa L. was shown. This
      increase can be assumed to be due to a de-novo synthesis of the enzyme.
      Chloramphenicol was found to inhibit this synthesis, whereas cycloheximide did
      not have any effect. Illumination with red light (660 nm) was followed by the
      same increase of porphobilinogen production as illumination with white light; far
      red (731 nm) did not induce such an effect. It is concluded that a phytochrome
      mediated mechanism is involved in the induction of delta-aminolaevulinate
      dehydratase synthesis. 

PMID- 24435264
TI  - [Differences in the temperature-dependence of the respiratory gas uptake of a
      chlorophyll-free Chlorella mutant in darkness and in blue light].
AB  - In the temperature range of 20-50 degrees C the O2-uptake of resting cells of a
      chlorophyll-free, carotenoid-containing mutant of Chlorella vulgaris Beijerinck
      (211-11h/20) in the dark is greatest at 47 degrees ; in blue light, however, it
      is highest at 32 degrees  (Fig. 1).A preceding one-hour exposure to temperatures
      of 15-45 degrees  in the dark affects neither the O2-uptake at subsequent 30
      degrees  in darkness nor its enhancement by blue light. Pre-exposure to 50
      degrees , however, results in a slightly decreased dark rate and in the absence
      of any blue light effect, while pre-incubation in 55-70 degrees  leads to almost
      complete suppression of the O2-uptake in darkness as well as under blue light
      (Fig. 2). The temperature dependence of the O2-consumption of cells supplied with
      1% of exogenous glucose in the dark shows an optimum around 36 degrees  (Fig.
      3a), which correlates with that of the temperature dependence of an active uptake
      of 3-O-methylglucose (Fig. 3b).The resemblance of these latter temperature
      dependencies to that of enhanced O2-uptake in blue light leads-together with
      Georgi's (Dr. thesis, Cologne, 1974) results of pulse chase experiments with
      [(14)C]glucose-to the discussion of an effect of blue light on intracellular
      membrane transport systems, which might result in a greater supply of sugar to
      the respiratory machinery. 

PMID- 24435265
TI  - A sulfotransferase from spinach leaves using adenosine-5'-phosphosulfate.
AB  - Active sulfotransferase can be extracted from spinach (Spinacea oleracea L.)
      leaves (and other higher plants) using a buffer system containing 0.1 M KCl and
      thiol reagents. This sulfotransferase is labile, it can, however, be stabilized
      by storage in 70% ammonium sulfate containing 10 mM mercaptoethanol. This extract
      will reduce labelled adenosine-5'-phosphosulfate (APS) and 3'-phosphoadenosine-5'
      phosphosulfate (PAPS) to acid-volatile radioactivity when dithioerythrol is
      added. The reduction from PAPS requires magnesium chloride and is inhibited by
      calcium chloride and sodium fluoride, whereas these chemicals have little effect
      on the APS-sulfotransferase activity. The reduction rates from both nucleotides
      are stimulated by increasing ionic strength and are inhibited by phosphate and
      cyanide. In the presence of non-labelled APS the acid-volatile radioactivity
      distilled from [(35)S] PAPS is drastically reduced, whereas the opposite
      experiment using [(35)S] APS in the presence of non-labelled PAPS has little
      effect. This indicates that APS is an obligatory intermediate in the conversion
      of [(35)S] PAPS to acid-volatile radioactivity. It is therefore concluded that
      the sulfotransferase from spinach is specific for APS. Activity with APS as
      sulfur-donor was found in 5 other plants in addition to spinach: Pennisetum, Zea
      (Gramineae); Brassica (Cruciferae); Helianthus (Compositae); and Vicia
      (Papilionaceae). These experiments demonstrate the use of APS for assimilatory
      sulfate reduction in higher plants. This has been shown previously for the green
      alga Chlorella. 

PMID- 24435266
TI  - [On the enlargement of the contact area between chloroplasts and the cytoplasmic
      environment by formation of tubular protrusions of the plastid envelope].
AB  - In the cells of yellow-green young leaves of the hybrid Oenothera (atrovirens x
      biennis) pingens . rubens with biennis plastids there are chloroplasts which
      possess tubuli extending from the outer limiting membrane into the cytoplasm. The
      tubuli have an average diameter of 40-50 nm; their length may reach at least 1
      MUm. They may branch and form a network. Occasionally they are in contact with
      the tonoplast, the plasmalemma, the endoplasmic reticulum or the dictyosomes.
      Series of adjacent sections show that membrane connections by such tubuli exist
      between chloroplasts and mitochondria or between different chloroplasts. Similar
      tubuli may also protrude from the inner limiting membrane of the chloroplasts
      into the plastid stroma. The possible function of the tubular chloroplast
      protrusions is discussed. 

PMID- 24435267
TI  - Effect of light on nucleic-acid synthesis and polyploidy level in elongating
      epicotyl cells of Pisum sativum.
AB  - The synthesis of DNA and RNA and the increase in dry matter were followed in the
      elongating cells of the epicotyl of peas (Pisum sativum L.) germinating in total
      darkness or in continuous light. The amounts of DNA and RNA per epicotyl were
      estimated by chemical methods, the amount of DNA per cell was measured by
      histophotometric techniques. The increase in DNA, RNA and dry matter in the
      epicotyl cells is much higher during germination in darkness than in light.
      During elongation in the dark most cortical epicotyl cells reach the 8C
      polyploidy level, in the light only the 4C polyploidy level is reached. A
      decrease in RNA synthesis is in agreement with a reduction in nuclear volume. 

PMID- 24435268
TI  - Studies of seed development in Pisum sativum : I. Seed size in reciprocal
      crosses.
AB  - Variation in cell population size and cell weight in the cotyledons are important
      factors in determining seed weight in Pisum sativum. The regulation of these
      parameters as well as that of growth rate has been examined. The use of
      reciprocal crosses between varieties of contrasting seed size has allowed the
      recognition of two systems of control-an intrinsic one dependent on the seed's
      own genotype, and the extrinsic control of the maternal environment. It is shown
      that the use of particular kinds of crosses can aid in discriminating the
      separate roles of sinks and sources as determinants of seed size. 

PMID- 24435269
TI  - Studies of seed development in Pisum sativum : II. Ribosomal RNA contents in
      reciprocal crosses.
AB  - Comparisons have been made at different developmental stages of the amounts of
      ribosomal RNA (rRNA) and of DNA in the cotyledons of two varieties of peas having
      different seed sizes. That with large seed has more rRNA per cell. The nature of
      the control of rRNA has been examined by the use of reciprocal crosses between
      the varieties. rRNA contents in the cells of a seed are not primarily dependent
      on the amounts of rDNA in those cells, but are regulated by the maternal parent;
      two hypotheses of the nature of this control are considered. 

PMID- 24435270
TI  - Further studies on the relationship between the rates of nitrate uptake, growth
      and conductivity changes in the medium of plant cell suspension cultures.
AB  - The changes in packed cell volume and in nitrate content and conductivity of the
      medium during the growth cycle of cell suspension cultures from Petroselinum
      hortense Hoffm., Glycine max Merr., and Haplopappus gracilis A. Grey in a
      chemically defined medium were compared. In all three cases sigmoidal curves
      obtained for large decreases in the conductivity were paralleled by similar
      curves for the rates of nitrate depletion from the medium until this nutrient was
      completely exhausted. Further decreases in the conductivity subsequent to
      nitrogen starvation proceeded at relatively slow rates and ceased when the
      cultures entered into the stationary phase of the growth cycle. Thus the
      previously reported method of deriving growth curves indirectly from conductivity
      measurements (Hahlbrock and Kuhlen, Planta 108: 271-278, 1972; Hahlbrock et al.,
      Planta 118: 75-84, 1974) might be generally applicable for this particular
      medium. The method seems to be based on a continuous uptake by the cells of ionic
      constituents throughout all stages of actual growth, even beyond the stage of
      nitrate exhaustion.Cell suspension cultures from Cicer arietinum L. and Acer
      pseudoplatanus L. in two different, more complex media were used for similar
      experiments, in which the changes in packed cell volume and in the conductivity
      of the medium were recorded. As with the results obtained with the fully
      synthetic medium, the mirror-images of the curves obtained for the decline in
      conductivity initially paralleled the growth curves. However, the two curves
      became incongruous after a certain growth stage was reached. These results are
      discussed with respect to the composition of the media used and to the apparent
      limitations of the method of determining specific growth stages by monitoring
      conductivity changes in the medium. 

PMID- 24435271
TI  - Red light induced production of gibberellin-like substances in homogenates of
      etiolated wheat leaves and in suspensions of intact etioplasts.
AB  - Homogenates of etiolated wheat leaves contain increased levels of acidic
      gibberellin (GA)-like substances following treatment with red light. Differential
      centrifugation of homogenates indicates that the response is confined to the 1000
      g (or plastid) fraction. Irradiation of suspensions of intact etioplasts also
      increases the level of extractable GA-like activity. Phytochrome can be detected
      spectrophotometrically in preparations of etioplasts. The response in etioplasts
      can be inhibited by chloramphenicol, but not by cycloheximide, and partially by
      Amo 1618. The GA-like substances produced in etioplasts seem capable of passing
      into the surrounding medium within 20 min. 

PMID- 24435273
TI  - Editorial.

PMID- 24435272
TI  - Relationship between femur neck bone mineral density and prevalent chronic
      obstructive pulmonary disease (COPD) or COPD mortality in older non-Hispanic
      white adults from NHANES III.
AB  - SUMMARY: The relationship between femur neck bone mineral density (FNBMD),
      prevalent COPD, and COPD mortality was examined in older non-Hispanic white
      adults from NHANES III. FNBMD was significantly related to prevalent COPD and
      COPD mortality before and after adjusting for shared risk factors. INTRODUCTION:
      Bone mineral density (BMD) has been linked to chronic obstructive pulmonary
      disease (COPD), but little is known about its relationship with COPD mortality.
      The present study examined the relationship between FNBMD, prevalent COPD, and
      COPD mortality in older non-Hispanic white adults from the third National Health
      and Nutrition Examination Survey (NHANES III, 1988-1994). METHODS: COPD status at
      baseline was defined by self-reported physician's diagnosis and by airway
      obstruction based on spirometry measurements in 3,275 non-Hispanic whites aged 50
      years and older. COPD mortality cases were identified using linked mortality
      records obtained through 2006. FNBMD was measured by dual-energy x-ray
      absorptiometry. Multiple regression was used to examine the baseline relationship
      between COPD and FNBMD. Cox proportional hazards models were used to estimate the
      hazards ratio (HR) for COPD mortality by FNBMD. RESULTS: Twelve percent self
      reported a physician's diagnosis of COPD, 23 % had mild or moderate airway
      obstruction, and 9 % had severe or very severe airway obstruction. There were 180
      COPD mortality cases in the sample. FNBMD was significantly lower in those with
      self-reported COPD diagnosis or airway obstruction before and after adjusting for
      shared risk factors (p < 0.05). COPD mortality risk was significantly increased
      for each standard deviation decline in FNBMD before (by 68 %) and after (by 26-38
      %) adjusting for shared risk factors. CONCLUSIONS: Low FNBMD was associated with
      both baseline COPD and future COPD mortality. Shared risk factors appeared to
      explain some, but not all, of these relationships.

PMID- 24435274
TI  - Phycobilisome structure and function.
AB  - Phycobilisomes are aggregates of light-harvesting proteins attached to the stroma
      side of the thylakoid membranes of the cyanobacteria (blue-green algae) and red
      algae. The water-soluble phycobiliproteins, of which there are three major
      groups, tetrapyrrole chromophores covalently bound to apoprotein. Several
      additional protiens are found within the phycobilisome and serve to link the
      phycobiliproteins to each other in an ordered fashion and also to attach the
      phycobilisome to the thylakoid membrane. Excitation energy absorbed by
      phycoerythrin is transferred through phycocyanin to allophycocyanin with an
      efficiency approximating 100%. This pathway of excitation energy transfer,
      directly confirmed by time-resolved spectroscopic measurements, has been
      incorporated into models describing the ultrastructure of the phycobilisome. The
      model for the most typical type of phycobilisome describes an allophycocyanin
      containing core composed of three cylinders arranged so that their longitudinal
      axes are parallel and their ends form a triangle. Attached to this core are six
      rod structures which contain phycocyanin proximal to the core and phycoerythrin
      distal to the core. The axes of these rods are perpendicular to the longitudinal
      axis of the core. This arrangement ensures a very efficient transfer of energy.
      The association of phycoerythrin and phycocyanin within the rods and the
      attachment of the rods to the core and the core to the thylakoid require the
      presence of several 'linker' polypeptides. It is recently possible to assemble
      functionally and structurally intact phycobilisomes in vitro from separated
      components as well as to reassociate phycobilisomes with stripped thylakoids.
      Understanding of the biosynthesis and in vivo assembly of phycobilisomes will be
      greatly aided by the current advances in molecular genetics, as exemplified by
      recent identification of several genes encoding phycobilisome components.Combined
      ultrastructural, biochemical and biophysical approaches to the study of
      cyanobacterial and red algal cells and isolated phycobilisome-thylakoid fractions
      are leading to a clearer understanding of the phycobilisome-thylakoid structural
      interactions, energy transfer to the reaction centers and regulation of
      excitation energy distribution. However, compared to our current knowledge
      concerning the structural and functional organization of the isolated
      phycobilisome, this research area is relatively unexplored. 

PMID- 24435275
TI  - Chlorophyll-protein complex composition and photochemical activity in developing
      chloroplasts from greening barley seedlings.
AB  - The time course for the observation of intact chlorophyll-protein (CP) complexes
      during barley chloroplast development was measured by mild sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The procedure required extraction of
      thylakoid membranes with sodium bromide to remove extrinsic proteins. During the
      early stages of greening, the proteins extracted with sodium bromide included
      polypeptides from the cell nucleus that associate with developing thylakoid
      membranes during isolation and interfere with the separation of CP complexes by
      electrophoresis. Photosystem I CP complexes were observed before the photosystem
      II and light-harvesting CP complexes during the initial stages of barley
      chloroplast development. Photosystem I activity was observed before the
      photosystem I CP complex was detected whereas photosystem II activity coincided
      with the appearance of the CP complex associated with photosystem II. Throughout
      chloroplast development, the percentage of the total chlorophyll associated with
      photosystem I remained constant whereas the amount of chlorophyll associated with
      photosystem II and the light-harvesting complex increased. The CP composition of
      thylakoid membranes from the early stages of greening was difficult to quantitate
      because a large amount of chlorophyll was released from the CP complexes during
      detergent extraction. As chloroplast development proceeded, a decrease was
      observed in the amount of chlorophyll released from the CP complexes by detergent
      action. The decrease suggested that the CP complexes were stabilized during the
      later stages of development. 

PMID- 24435276
TI  - Continuous recording of photochemical and non-photochemical chlorophyll
      fluorescence quenching with a new type of modulation fluorometer.
AB  - A newly developed fluorescence measuring system is employed for the recording of
      chlorophyll fluorescence induction kinetics (Kautsky-effect) and for the
      continuous determination of the photochemical and non-photochemical components of
      fluorescence quenching. The measuring system, which is based on a pulse
      modulation principle, selectively monitors the fluorescence yield of a weak
      measuring beam and is not affected even by extremely high intensities of actinic
      light. By repetitive application of short light pulses of saturating intensity,
      the fluorescence yield at complete suppression of photochemical quenching is
      repetitively recorded, allowing the determination of continuous plots of
      photochemical quenching and non-photochemical quenching. Such plots are compared
      with the time courses of variable fluorescence at different intensities of
      actinic illumination. The differences between the observed kinetics are
      discussed. It is shown that the modulation fluorometer, in combination with the
      application of saturating light pulses, provides essential information beyond
      that obtained with conventional chlorophyll fluorometers. 

PMID- 24435277
TI  - The amino acid sequences of the cytochromes c553 from Porphyridium cruentum and
      Aphanizomenon flos-aquae.
AB  - The amino acid sequences of cytochrome c553 from the eukaryotic red alga
      Porphyridium cruentum and from the prokaryotic cyanobacterium Aphanizomenon flos
      aquae have been determined from the tryptic and cyanogen bromide peptides. The
      results indicate that a charged region of these proteins has evolved with special
      rapidity to accomodate a rapid evolution of a binding site in the P700 electron
      acceptor complex. 

PMID- 24435278
TI  - Selective photobleaching of PSI-related chlorophylls in heat-stressed pea
      chloroplasts.
AB  - Measurements of electron transport activity point to the occurrence of major
      changes in the organisation of the photosynthetic apparatus of heat-stressed
      chloroplasts. One of the consequences of these changes is shown to be a greatly
      increased susceptibility of chlorophyll to photobleaching. Despite the fact that
      the threshold temperature for this photobleaching coincides closely with that for
      the inhibition of PSII activity, the bleached components were found to be
      specifically associated with PSI. This increased susceptibility of PSI pigments
      to photobleaching is shown to be a direct consequence of an interruption of the
      flow of reductants from PSII to PSI that would normally protect PSI from
      photooxidation. 

PMID- 24435279
TI  - Improved rates of CO2-fixation by intact chloroplasts isolated in media with KCl
      as the osmoticum.
AB  - Intact chloroplasts were isolated from spinach leaves using media with either 330
      mM sorbitol or 200 mM KCl as the osmoticum. Chloroplasts isolated in KCl
      exhibited higher rates of CO2-dependent oxygen evolution in nine out of ten
      experiments, the average increase being 43%. Chloroplasts isolated in KCl
      routinely achieved rates of CO2-dependent oxygen evolution of 200-300 MU mol.mg
      chlorophyll(-1).hour(-1) at 20 degrees C. Intact chloroplasts were also isolated
      in media with 200 mM NaCl or choline chloride but the rates of CO2 fixation were
      not superior to those isolated in sorbitol media. The K(+) content of
      chloroplasts isolated in KCl media was higher than for chloroplasts isolated in
      sorbitol. It is suggested that the use of KCl as an osmoticum prevents the loss
      of chloroplast K(+) which can occur during isolation in sorbitol media.
      Chloroplasts isolated in KCl lost, on average, 36% of the initial CO2 fixation
      activity after storage for four hours on ice, compared to 24% loss of activity
      for chloroplasts isolated in sorbitol. This increased loss of activity was not
      observed if KCl was used in the grinding medium and sorbitol or glycinebetaine in
      the resuspension media. For measurement of the maximum photosynthetic capacity in
      vitro, the use of KCl in the grinding medium may be better than sorbitol. 

PMID- 24435280
TI  - Effects of irradiance and temperature on photosynthesis in C3, C 4 and C 3/C 4
      Panicum species.
AB  - Species in the Laxa and Grandia groups of the genus Panicum are adapted to low,
      wet areas of tropical and subtropical America. Panicum milioides is a species
      with C3 photosynthesis and low apparent photorespiration and has been classified
      as a C3/C4 intermediate. Other species in the Laxa group are C3 with normal
      photorespiration. Panicum prionitis is a C4 species in the Grandia group. Since
      P. milioides has some leaf characteristics intermediate to C3 and C4 species, its
      photosynthetic response to irradiance and temperature was compared to the closely
      related C3 species, P. laxum and P. boliviense and to P. prionitis. The response
      of apparent photosynthesis to irradiance and temperature was similar to that of
      P. laxum and P. boliviense, with saturation at a photosynthetic photo flux
      density of about 1 mmol m(-2) s(-1) at 30 degrees C and temperature optimum near
      30 degrees C. In contrast, P. prionitis showed no light saturation up to 2 mmol
      m(-2) s(-1) and an optimum temperature near 40 degrees C. P. milioides exhibited
      low CO2 loss into CO2-free air in the light and this loss was nearly insensitive
      to temperature. Loss of CO2 in the light in the C3 species, P. laxum and P.
      boliviense, was several-fold higher than in P. milioides and increased 2- to 5
      fold with increases in temperature from 10 to 40 degrees C. The level of dark
      respiration and its response to temperature were similar in all four Panicum
      species examined. It is concluded that the low apparent photorespiration in P.
      milioides does not influence its response of apparent photosynthesis to
      irradiance and temperature in comparison to closely related C3 Panicum species. 

PMID- 24435281
TI  - A correlation between changes in luminescence decay kinetics and the appearance
      of a CO2-accumulating mechanism in Scenedesmus obliquus.
AB  - In experiments with the unicellular green algae Scenedesmus obliquus a
      correlation was found between the presence of the CO2-accumulating mechanism and
      the appearance of polyphasic luminescence decay kinetics. A potentiometric
      titration method was used to measure and calculate photosynthetic carbon
      uptake.Polyphasic luminescence decay kinetics was found when the algae showed
      photosynthetic characteristics typical of algae adapted to low-CO2 conditions.
      When high-CO2 grown algae were transferred to low-CO2 conditions they gradually
      developed polyphasic decay kinetics during the first 25-30 minutes. When low-CO2
      grown algae were transferred to high-CO2 conditions the polyphasic decay kinetics
      disappeared. To account for these results a working hypothesis is presented on
      the basis of the energy requirement for a CO2-accumulating mechanism. 

PMID- 24435282
TI  - Vibronic coupling to electron transfer and the structure of the R. Viridis
      reaction center.
AB  - This paper points out that the orientations of the porphyrins,
      bacteriochlorophyll and bacteriopheophytin, in the reaction centers of
      Rhodopseudomonas viridis, as shown by the new X-ray determined structure, have a
      peculiar orientation towards each other: electron donors are broadside toward the
      acceptors and acceptors are edgeon toward donors. Vibronic coupling which is the
      mechanism of converting free-energy loss in electron transport to vibrational
      energy is examined as a possible explanation. Preliminary calculations do not
      support this as an explanation of the orientations but suggest strongly that the
      non-heme iron atom has the function of promoting vibronic coupling in the
      electron transfer from bacteriopheophytin to menaquinone. It is further suggested
      that the system of electron transport from the special pair of
      bacteriochlorophyll to the bacteriopheophytin is arranged to keep virbonic
      coupling to a minimum to match the very small electronic free-energy loss in this
      region. 

PMID- 24435283
TI  - Phytotron cultivation of early barley mutants.
AB  - CONCLUSIONS: The authors have tried to gather data which permit some information
      on the between and within locus reactions of induced early barley mutants to
      different photo- and thermoperiods. Eight mutant cases, showing rather drastic
      earliness in field cultivation and representing three different gene loci, were
      examined in phytotron experiments according to routine methods of cultivation.
      One of the mutants, mat-a (8), has been released as an original Swedish barley
      variety under the name of Svalof's Mari. In a previous publication (DORMLING et
      al., 1966) this mutant was compared to its parent variety, Svalof's Bonus, under
      30 different climatic conditions. In the present investigation three photoperiods
      (24, 16 and 8 hours of artificial light) were combined with three suitable
      thermoperiods (20-15 degrees , 20-10 degrees  and 15-10 degrees C).The results
      indicate that photoperiodic insensitivity, with regard to ear formation and
      heading capacity, as well as kernel production, is of rather frequent occurrence
      in connection with drastically early mutants in barley. Four out of eight induced
      mutants give a more or less pronounced insensitivity. Three of the four
      insensitive mutants represent locus a, one belongs to locus b. Of the two c
      mutants none was insensitive; both were on the contrary pronounced long-day
      types.Photo- and thermoperiods interact in various ways. This is especially clear
      in the c-mutants just mentioned, which have a high generative productivity and
      efficiency at continuous light and high thermoperiods. They produce no grain but
      considerable vegetative matter at 8 hours of light, independently of
      thermoperiod, as well as at 16 hours of light with high temperatures. In fact,
      mutants of loci a and c differ strikingly with regard to their relations to the
      climatic conditions applied. The insensitive mutant b (13) is remarkably similar
      to the mutant a (12), but its resemblance to the sensitive mutants b (7) and b
      (10) of the same locus is evidenced by its high average internode number.It ought
      to be pointed out here that the mutants of the three gene loci analysed in this
      study can be distinguished phenotypically with regard to morphological as well as
      physiological properties, in the field as well as in phytotron cultivation. The c
      mutants are especially characteristic. However, there also seem to be clear
      differences in reaction between the allelic mutants of a locus. In fact, all
      eight mutants studied seem to react more or less differently.The insensitive
      mutant a (8), which has been released into practice, is also widely used in
      recombination work, and successful segregates have been isolated. The
      characteristics of a (8), which make the mutant valuable in practice, are also
      found in phytotron experimentation, specially with regard to earliness,
      generative efficiency and yield. Also the semidwarf habit and the insensitivity
      to changes in photo- and thermoperiods readily show up.

PMID- 24435284
TI  - [Studies on the significance of vegetative nuclei and their nucleoli in pollen
      grains and pollen tubes].
AB  - The communication deals with a study of the significance of vegetative nuclei of
      pollen grains. The study of vegetative nuclei was performed with pollen grains
      and pollen tubes of a tulip (Tulipa gesneriana, var. Bellona).The conclusions are
      summarized as follows: 1. The vegetative nucleus does not participate directly in
      the regulation of growth of the pollen tubes. 2. Stimulation of the growth of
      pollen tubes induced by means of boric acid is not accompanied by a simultaneous
      stimulation of spiralization of chromosomes in the generative nucleus or by its
      division. 3. The vegetative nucleus and its nucleolus take part in the division
      of the generative nucleus. 4. In the course of spiralization of the chromosomes
      of the generative nucleus, the nucleolus disappears from the vegetative nucleus.
      The vegetative nucleus, however, persists in spite of a decrease in DNA content.
      5. The vegetative nucleus disappears after formation of spermatic nuclei. 

PMID- 24435285
TI  - Direct evidence for models of heterosis provided by mutants of Arabidopsis
      blocked in the thiamine pathway.
AB  - Auxotrophic mutants genetically blocked at different steps of the thiamine
      pathway dramatically demonstrate the biochemical mechanism of hybrid vigor due to
      simple and perfect dominance at two unlinked loci. Heteroallelic hybrids of
      mutants requiring the pyrimidine moiety of thiamine display allelic
      complementation and thus furnish clear biochemical and genetic evidence for the
      superdominance hypothesis. Hybrids of low- and high-temperature-requiring leaky
      mutants demonstrate that heterozygosity at a single gene locus may confer
      developmental homeostasis on the heteroallelic combinations superior to that of
      the homoallelic parents. The results of this study on the autogamous plant,
      Arabidopsis, and of recent reports on the outbreeding species, Drosophila, render
      untenable the generalization that high versus low temperature dependent heterosis
      is determined by the breeding system.ZUSAMMENFASSUNG: Auxotrophe Arabidopsis
      Mutanten, bei denen verschiedene Schritte der Thiaminsynthese genetisch blockiert
      sind, lassen deutlich den biochemischen Mechanismus der Heterosis erkennen, der
      auf einfacher und volliger Dominanz in zwei ungekoppelten Loci beruht.
      Heteroallele Hybriden von Mutanten, die den Pyrimidinanteil des Thiamins
      benotigen, zeigen allele Komplementation und liefern damit den klaren
      biochemischen und genetischen Beweis fur die Superdominanz-Hypothese. Hybriden
      von leaky-Mutanten, die einen niedrigen bzw. hohen Temperaturbedarf haben,
      zeigen, dabeta Heterozygotie in einem einzelnen Genlocus den heteroallelen
      Kombinationen eine Entwicklungshomeostasie verleihen kann, die grobetaer als die
      der homoallelen Eltern ist. Die Ergebnisse unserer Untersuchungen an der
      autogamen Pflanze Arabidopsis und neuere Ergebnisse bei Drosophila lassen die
      Verallgemeinerung, dabeta die Art der Temperaturabhangigkeit der Heterosis durch
      das Zuchtsystem bestimmt wird, nicht zu. 

PMID- 24435286
TI  - [Inheritance of fin characters in the Guppy (Lebistes reticulatus Peters)].
AB  - 1. A new dominant autosomal mutation of Lebistes reticulatus is described,
      causing a veil-like elongation of fins and increased dichotomous branching of fin
      rays. The dominant gene Kal, responsible for the formation of veil-fins, can be
      suppressed by a non-allelic dominant factor Sup. Kal and Sup belong to two
      different linkage groups. 2. Either Kal or Sup are linked with the dominant
      allele of the recessive xanthoric factor "blond", because blond veil-fin guppies
      could not be obtained by recombination. 3. Homozygosity for the recessive
      wildtype alleles of the gene for veil-fins and of its suppressor, (i.e. + (Kal)
      /+ (Kal) , + (Sup) /+ (Sup) ) seems to result in postnatal lethality of the
      males. 

PMID- 24435287
TI  - Quantitative genetics of sugarcane : III. Potential for sucrose selection in
      Saccharum spontaneum.
AB  - 1. A project has been initiated to explore the possibilities of selection for
      higher levels of sucrose storage in the wild species S. spontaneum, using a
      representative sample of parental clones under conditions of natural crossing. 2.
      The aim of the programme is the development of superior clones to represent the
      wild species in conventional breeding programmes, which involve repeated
      backcrossing to S. officinarum. 3. An analysis of the first generation following
      the intercrossing of 21 parental types without emasculation, has demonstrated
      extensive genetic variability within and between progeny groups for fibre,
      sucrose, reducing sugars and yield grade. 4. Fibre and sucrose percent fresh
      weight are characters of high repeatability (0.4-0.6), and show little evidence
      of non-additive genetic effects. Individual plant performance for these
      characters can therefore be taken as a satisfactory basis for selection in this
      material. 5. The average degree of self-fertilization occurring under conditions
      of natural crossing has been estimated to be 0.69+/-.13, based on analyses of the
      quantitative genetic data for fibre and sucrose percent fresh weight. 6. The
      within-family genetic variance observed is of the order of five times that
      expected if the parental clones were homozygous. Much of the genetic variability
      induced within-families is therefore due to self-fertilization of heterozygous
      parental material, though the exact proportion cannot be deduced from the present
      data. 7. The initial response to selection for increased sucrose percent fresh
      weight is predicted to be of the order of 50% of the population mean. Comparable
      responses in subsequent cycles of the programme appear to be possible, provided
      an adequate degree of outcrossing can be achieved by controlled pollination
      techniques. 8. The genetic correlations between sucrose and other characters of
      importance are favourable to the objectives of the breeder, or else of a low
      order. There is no general relationship between the somatic chromosome number of
      the parental clones and the mean sucrose level of their progeny. 

PMID- 24435288
TI  - Serial analysis of combining ability in diallel and fractional diallel crosses in
      linseed.
AB  - An analysis of the nature of the gene action for seven characters influencing
      productivity and wide adaptation in Linum usitatissimum L. was undertaken in this
      investigation over three seasons based on diallel and fractional diallel crosses,
      among a set of ten genetically diverse parents. Estimation of combining ability
      and the nature of geno-type-environment interactions for the above characters was
      also examined.A comparison of the means of the parents and hybrids over three
      environments showed positive heterosis for height, number of tillers, fruit
      bearing branches and capsules per plant while negative heterosis was observed for
      flowering time. The remaining two characters viz., height at branching and seeds
      per five capsules showed little differences due to mutual cancellation of the
      components of heterosis.A serial analysis of combining ability over three seasons
      using GRIFFING's model (1956) has revealed significant sea-sonal effects on the
      estimates of combining ability effects. Additive gene action was found to be
      predominant in most of the characters although non-additive variation due to
      s.c.a. was equally prominent for fruit-bearing branches and capsules per plant.
      On the basis of g.c.a. for all the characters, M. 10 and N. 55, both Peninsular
      types were the best followed by N.P. (R.R.) 45 and Mohaba Local.In the fractional
      diallel analysis the relative estimates g.c.a. and s.c.a. were similar for s=9
      and 7. However, there was overestimation in favour of s.c.a. when s was reduced
      to 3. The serial analysis of fractional diallel had confirmed the results of full
      diallel. Significant genotype x environment interactions for flowering time,
      height, height at branching, fruit-bearing branches and capsules per plant were
      observed in this analysis also. The results have indicated that reduction of the
      diallel to a fraction with s=n/2 would vitiate the order and precision of
      estimates of combining ability.The analysis of genotype x environment indicated
      that the pattern of interactions among the parents of different geographical
      groups was not similar but varied with the character under study. Considerable
      interactions were observed for capsules per plant, fruit-bearing branches and
      flowering time in that order respectively. A comparison of the parental and
      hybrid populations for the degree of interaction for all the characters had
      revealed that heterozygosis might not at all be directly related to the degree of
      homeostasis. Actually, heterozygotes were found to show more interactions than
      homozygotes for flowering time, height at branching and tiller number and lower
      interactions for the other four characters. Significant seasonal effect on the
      degree of heterosis for vegetative as well as reproductive characters was
      observed in a majority of F1's with variable degree of dominance. 

PMID- 24435289
TI  - An ecological function and services approach to total maximum daily load (TMDL)
      prioritization.
AB  - Prioritizing total maximum daily load (TMDL) development starts by considering
      the scope and severity of water pollution and risks to public health and aquatic
      life. Methodology using quantitative assessments of in-stream water quality is
      appropriate and effective for point source (PS) dominated discharge, but less so
      in watersheds with mostly nonpoint source (NPS) related impairments. For NPSs,
      prioritization in TMDL development and implementation of associated best
      management practices should focus on restoration of ecosystem physical functions,
      including how restoration effectiveness depends on design, maintenance and
      placement within the watershed. To refine the approach to TMDL development,
      regulators and stakeholders must first ask if the watershed, or ecosystem, is at
      risk of losing riparian or other ecologically based physical attributes and
      processes. If so, the next step is an assessment of the spatial arrangement of
      functionality with a focus on the at-risk areas that could be lost, or could,
      with some help, regain functions. Evaluating stream and wetland riparian function
      has advantages over the traditional means of water quality and biological
      assessments for NPS TMDL development. Understanding how an ecosystem functions
      enables stakeholders and regulators to determine the severity of problem(s),
      identify source(s) of impairment, and predict and avoid a decline in water
      quality. The Upper Reese River, Nevada, provides an example of water quality
      impairment caused by NPS pollution. In this river basin, stream and wetland
      riparian proper functioning condition (PFC) protocol, water quality data, and
      remote sensing imagery were used to identify sediment sources, transport,
      distribution, and its impact on water quality and aquatic resources. This study
      found that assessments of ecological function could be used to generate leading
      (early) indicators of water quality degradation for targeting pollution control
      measures, while traditional in-stream water quality monitoring lagged in response
      to the deterioration in ecological functions. 

PMID- 24435291
TI  - Experimental modelling of single-particle dynamic processes in crystallization by
      controlled colloidal assembly.
AB  - In the last few decades, the controlled colloidal assembly was adopted as a new
      modelling technology for the study of the crystallization mechanism. In colloidal
      systems, the movement of particles is slow enough to follow and the particle
      dynamics can be monitored at the single-particle level using normal optical
      microscopes. So far, the studies of colloidal crystallization have produced a
      number of insights, which have significantly improved our understanding of
      crystallization. In this review, we summarize the recent advances in
      understanding the mechanism of crystallization, which were achieved using
      colloidal model systems, i.e., the kinetics of nucleation, growth and defect
      formation. Such model systems allow us to not only visualize some "atomic"
      details of nucleation and surface processes of crystallization, but also quantify
      previous models to such an extent that has never been achieved before by other
      approaches. In the case of nucleation, the quantitative observation of the
      kinetic process was made at the single-particle level; the results include the
      ideal case and the deviations from classical theories. The deviations include
      multi-step crystallization, supersaturation-driven structural mismatch
      nucleation, defect creation and migration kinetics, surface roughening, etc. It
      can be foreseen that this approach will become a powerful tool to study the
      fundamental process of crystallization and other phase transitions. 

PMID- 24435292
TI  - Efficient synthesis of narrowly dispersed hydrophilic and magnetic molecularly
      imprinted polymer microspheres with excellent molecular recognition ability in a
      real biological sample.
AB  - A facile and highly efficient approach to obtain narrowly dispersed hydrophilic
      and magnetic molecularly imprinted polymer microspheres with molecular
      recognition ability in a real biological sample as good as what they show in the
      organic solvent-based media is described for the first time. 

PMID- 24435293
TI  - [Ten years of early complex geriatric rehabilitation therapy in the DRG system].
AB  - BACKGROUND: Geriatric medicine, as a specialized form of treatment for the
      elderly, is gaining in importance due to demographic changes. Especially
      important for geriatric medicine is combining acute care with the need to
      maintain functionality and participation. This includes prevention of dependency
      on structured care or chronic disability and handicap by means of rehabilitation.
      METHODS AND MATERIALS: Ten years ago, the German DRG system tried to incorporate
      procedures (e.g., "early rehabilitation in geriatric medicine") in the hospital
      reimbursement system. OPS 8-550.x, defined by structural quality, days of
      treatment, and number of therapeutic interventions, triggers 17 different
      geriatric DRGs, covering most of the fields of medicine. OPS 8-550.x had been
      revised continuously to give a clear structure to quality aspects of geriatric
      procedures. However, OPS 8-550.x is based on proven need of in-hospital
      treatment. In the last 10 years, no such definition has been produced taking
      aspects of the German hospital system into account as well as aspects of
      transparency and benefit in everyday work. RESULTS: The German DRG system covers
      just basic reimbursement aspects of geriatric medicine quite well; however, a
      practicable and patient-oriented definition of "hospital necessity" is still
      lacking, but is absolutely essential for proper compensation. A further problem
      concerning geriatric medicine reimbursement in the DRG system is due to the
      different structures of providing geriatric in-hospital care throughout Germany.

PMID- 24435290
TI  - Neuropsychiatric adverse events associated with statins: epidemiology,
      pathophysiology, prevention and management.
AB  - Statins, or 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, such as
      lovastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin and
      pitavastatin, are cholesterol-lowering drugs used in clinical practice to prevent
      coronary heart disease. These drugs are generally well tolerated and have been
      rarely associated with severe adverse effects (e.g. rhabdomyolysis). Over the
      years, case series and data from national registries of spontaneous adverse drug
      reaction reports have demonstrated the occurrence of neuropsychiatric reactions
      associated with statin treatment. They include behavioural alterations (severe
      irritability, homicidal impulses, threats to others, road rage, depression and
      violence, paranoia, alienation, antisocial behaviour); cognitive and memory
      impairments; sleep disturbance (frequent awakenings, shorter sleep duration,
      early morning awakenings, nightmares, sleepwalking, night terrors); and sexual
      dysfunction (impotence and decreased libido). Studies designed to investigate
      specific neuropsychiatric endpoints have yielded conflicting results. Several
      mechanisms, mainly related to inhibition of cholesterol biosynthesis, have been
      proposed to explain the detrimental effects of statins on the central nervous
      system. Approaches to prevent and manage such adverse effects may include drug
      discontinuation and introduction of dietary restrictions; maintenance of statin
      treatment for some weeks with close patient monitoring; switching to a different
      statin; dose reduction; use of omega-3 fatty acids or coenzyme Q10 supplements;
      and treatment with psychotropic drugs. The available information suggests that
      neuropsychiatric effects associated with statins are rare events that likely
      occur in sensitive patients. Additional data are required, and further clinical
      studies are needed. 

PMID- 24435294
TI  - Depressive symptoms before and after long-term CPAP therapy in patients with
      sleep apnea.
AB  - BACKGROUND: The outcome of depressive symptoms under CPAP therapy for OSA
      hypopnea syndrome (OSAHS) has been poorly evaluated. In this multicenter,
      prospective cohort study, we evaluated the prevalence and correlates of
      persistent depressive symptoms after long-term CPAP therapy for OSAHS. METHODS:
      This study included 300 patients with OSAHS and depressive symptoms (13-item,
      self-rated Pichot depression scale [QD2A] >= 7) at diagnosis. The primary
      dependent variable was persistent depressive symptoms after >= 1 year of CPAP
      therapy. Multivariate regression analyses were performed to determine variables
      independently associated with the persistence of depressive symptoms. RESULTS:
      After an average of 529 days (range, 365-1,569 days) of CPAP therapy, the mean
      (SD) QD2A score decreased from 9.2 (2.0) to 5.4 (4.0) (P < .0001), but 125
      patients (41.7%) presented persistent depressive symptoms. The persistence of
      depressive symptoms was independently associated with persistent excessive
      daytime sleepiness (EDS) (OR, 2.72; 95% CI, 1.33-5.61), comorbid cardiovascular
      disease (OR, 1.76; 95% CI, 1.02-3.00), and female sex (OR, 1.53; 95% CI, 1.09
      2.13). A positive linear trend was observed for the adjusted OR of persistent
      depressive symptoms with decreasing CPAP effect on the Epworth sleepiness scale
      (P < .0001). CONCLUSIONS: CPAP therapy does not resolve depressive symptoms in
      many patients with OSAHS. Persistent depressive symptoms are strongly associated
      with EDS. Active monitoring of depressive symptoms is needed in patients with
      OSAHS who are treated with CPAP. Interventional trials are required to evaluate
      the impact of antidepressants, cognitive behavioral therapy, or both on comorbid
      depression in patients with OSAHS.

PMID- 24435295
TI  - Budding and cleavage division of tobacco mesophyll protoplasts in relation to
      pseudo-wall and wall formation.
AB  - Two saline media, differing primarily in the presence or absence of NH4 (+) but
      also in the concentration of sucrose, were developed for culture of tobacco
      (Nicotiana tabacum L.) mesophyll protoplasts. In the R0.6 medium, which does not
      contain NH4 (+) and only 1 g/l sucrose, protoplasts divide 2-3 times by budding
      and form only a pseudo-wall, i.e. a nonrigid structure containing
      polysaccharides. Later the cells degenerate, and sustained division does not take
      place. In the W 0.6 medium, which contains NH4 (+) and 30 g/l sucrose, the
      protoplasts form a rigid wall and divide by cleavage of the cells. After a few
      divisions, the walls of practically all of the newly formed cells degenerate into
      pseudo-walls, and the divisions cease. Only a few cells keep a wall, continue to
      divide, and form colonies. A very high frequency of colony formations from
      protoplasts is obtained by culturing protoplasts for a week in R0.6 or W 0.6 and
      then diluting the culture with a sugar medium. A detailled study of the inorganic
      and organic components of the saline media showed a strong interaction between
      the nitrogen supply and the cytokinin requirement. The advantages of the saline
      media in obtaining cell colonies from protoplasts, the problems associated with
      budding-type division, the causes of the cessation of division when no complete
      wall is formed, and the conditions necessary for wall formation are discussed. 

PMID- 24435296
TI  - Development of C4 photosynthesis in sugar cane: Changes in properties of
      phosphoenolpyruvate carboxylase during greening.
AB  - Phosphoenolpyruvate (PEP) carboxylase extracted from etiolated and greening sugar
      cane (a Saccharum hybrid) displayed different properties in terms of DEAE
      cellulose elution profile and activation by glucose-6-phosphate. During the first
      20 hours of greening, no increase in extractable PEP carboxylase activity was
      observed, but ionic and allosteric properties of the enzyme changed, becoming
      similar to those found for the enzyme from light-grown cane. Density labelling
      studies with deuterium oxide provided no evidence for either de novo synthesis or
      turnover of the enzyme during this period, or during the following 24 hours of
      greening. These results are discussed in relation to enzyme control mechanisms
      and the development of the C4 pathway in photosynthesis. 

PMID- 24435297
TI  - A photoperiodic response mediated by blue light in the brown alga Scytosiphon
      lomentaria.
AB  - The crustose phase of Scytosiphon lomentaria (Lyngb.) J. Ag. persists
      indefinitely in 16 h of white light per day, but produces erect, cylindrical
      thalli vegetatively in 8-h days. The critical daylength for this short-day (SD)
      response is sharply defined, and, between 12 and 13 h, differences in daylength
      of only 15 min produce substantial differences in response. A significant
      response to SD can be induced by as few as 4 SD cycles, but 10-12 cycles are
      required to saturate the response and induce more than 90% of the plants to form
      thalli. The response to SD is completely inhibited by a 1-min light-break with a
      low irradiance of blue light, given in the middle of a 16-h dark period, but is
      unaffected by longer periods and higher irradiances of red or far-red light.
      There is good reciprocity between the irradiance and the length of a light-break
      with blue light, and 50% inhibition of the response to SD is induced by about 2
      nE cm(-2) at 449 nm. All attempts to reverse the inhibitory effects of blue light
      by subsequent irradiation with another wavelength have so far failed. These
      results indicate that phytochrome is not the photoreceptor pigment for this
      response, in spite of the similarity of the response in all other respects to the
      photoperiodic responses of flowering plants and other algae. 

PMID- 24435298
TI  - Photoperiodism and enzyme rhythms: Kinetic characteristics of the photoperiodic
      induction of Crassulacean acid metabolism.
AB  - The effect of photoperiod on Crassulacean acid metabolism (CAM) in Kalanchoe
      blossfeldiana Poellniz, cv. Tom Thumb, has characteristics similar to its effect
      on flowering in this plant (although these two phenomena are not causally
      related). The photoperiodic control of CAM is based on (a) dependance on
      phytochrome, (b) an endogenous circadian rhythm of sensitivity to photoperiodic
      signals, (c) a balance between specific positive (increase in enzyme capacity)
      and negative (inhibitory substances) effects of the photoperiod. Variations in
      malate content, capacity of phosphoenolpyruvate (PEP) carboxylase, and capacity
      of CAM inhibitors in young leaves were measured under photoperiodic conditions
      noninductive for CAM and after transfer into photoperiodic conditions inductive
      for CAM. Essential characteristics of the photoperiodic induction of CAM are: 1)
      lag time for malate accumulation; 2) after-effect of the inductive photoperiod on
      the malate accumulation, on the increase in PEP carboxylase capacity, and on the
      decrease in the level of long-day produced inhibitors; final levels of malate,
      enzyme capacity and inhibitor are proportional to the number of inductive day
      night cycles; 3) cireadian rhythm in PEP carboxylase capacity with a fixed phase
      under noninductive photoperiods and a continuously shifting phase under inductive
      photoperiods, after complex advancing and delaying transients. Kinetic
      similarities indicate that photoperiodic control of different physiological
      functions, namely, CAM and flowering, may be achieved through similar mechanisms.
      Preliminary results with species of Bryophyllum and Sedum support this
      hypothesis. Phase relationships suggest different degrees of coupling between
      endogenous enzymic rhythm and photoperiod, depending on whether the plants are
      under long days or short days. 

PMID- 24435299
TI  - The formation of the fibrils in the lorica of Poteriochromonas stipitata: Tip
      growth, kinetics, site, orientation.
AB  - The microfibrils of the lorica of Poteriochromonas stipitata Scherffel obviously
      are formed at the surface of the plasmalemma. They elongate unidirectionally by
      tip growth. On 1 MUm(2) plasmalemma about 1-2*10(6) glycosidic bonds per minute
      are formed. In the stalk, the primary fibrils are arranged helically. They tend
      to fasciate; a ribbon-like fibril has the width of about 20 nm and, therewith,
      nearly that of a microtubule. Every primary fibril coincides precisely with a
      microtubule. The microtubules lie under the plasmalemma and are connected with it
      by cross bridges. The secondary fibrils form a more irregular network. They are
      mainly produced where and when microtubules are absent. They band zipper-like
      with each other and with the primary fibrils. It is discussed how the different
      structures which are involved in microfibril formation move and how the formation
      process is regulated. Microtubules obviously influence morphogenesis of the
      lorica: they participate in special orientation of microfibrils, but play no role
      in their synthesis and secretion. 

PMID- 24435300
TI  - Formation of C-4 dicarboxylic acids by intact spinach chloroplasts.
AB  - It is concluded from (14)C labelling kinetics as well as from enzyme analysis
      that formation of malate and aspartate from glycerate-3P via carboxylation of P
      enolpyruvate occurs in isolated photosynthesizing spinach (Spinacia oleracea L.)
      chloroplasts. Carbon incorporation into both dicarboxylic acids was about 1% of
      the total CO2 fixation. Both acids are suggested to act as substrates for counter
      exchange for glutamate and alpha-ketoglutarate. 

PMID- 24435301
TI  - [An interesting species for studies on the determination of the twining type in
      stems: Periploca graeca L. (asclepiadaceae)].
AB  - Periploca graeca plants develop simultaneously under both natural and controlled
      conditions, three types of shoots: short upright shoots, long twining shoots, and
      long creeping shoots. Short shoots can be compared with long shoots and long
      twining shoots with long non-twining shoots. The main stem passes successively
      through an upright stage and a twining stage. 

PMID- 24435302
TI  - The influence of the growth retardant CCC on endogenous gibberellin in cucumber
      seedlings.
AB  - The gibberellin content of cucumber (Cucumis sativus L.) roots and green organs
      from (2-chloroethyl) trimethylammonium chloride (CCC)-treated seeds was equal to
      or even higher than in the water controls. The main difference between control
      and growth retardant-treated seedlings was expressed in the differential
      distribution of the endogenous gibberellin between its free and bound forms. 

PMID- 24435303
TI  - Glutamine as a major acceptor of reduced nitrogen in leaves.
AB  - The feeding of K(15)NO3 via the xylem stream to photosynthesising leaves of
      Datura stramonium L. shows a massive routing of (15)N to glutamine, increasing
      with rise in the N-feeding level (between 0 and 400 MUg N ml(-1)). At each
      feeding level the glutamine and glutamate pools have very similar (15)N
      enrichment despite disparity in pool size. Amino-compound pool-size and (15)N
      enrichment do not increase above the 300 MUg ml(-1) feeding level which
      corresponds to the normal level of nitrate-N in the xylem stream of the
      experimental plants. Thus, the role of glutamine as an N storage compound and
      ammonia "detoxifier" in many plants extends to the incorporation of
      photosynthetically reduced N newly produced in Datura leaves; the level of N
      incorporation into glutamine is apparently dependent on the level of nitrate
      feeding and the degree of induction of nitrate-reducing enzymes. 

PMID- 24435304
TI  - Phytochrome-mediated rapid changes of cyclic AMP in mustard seedlings (Sinapis
      alba L.).
AB  - A 5-min red light pulse which operates exclusively through phytochrome leads to a
      strong but transient decrease of the level of cAMP in the cotyledons of the
      mustard seedling. The strongest response is observed approximately 30 min after
      the red light pulse. In the axis system (hypocotyl plus taproot) the red light
      pulse causes a rapid but modest increase of the cAMP contents. The question of
      whether the observed changes of the tissue contents of cAMP can be regarded as
      intermediate steps in the causal sequence between Pfr (far-red absorbing form of
      phytochrom) and some photoresponses is discussed. 

PMID- 24435305
TI  - Organ culture of Eucalyptus grandis L.
AB  - Organ culture of nodes of Eucalyptus grandis permitted the rooting of nodes from
      much beyond No. 14, the highest node from which rooting has been described so
      far, namely up to node No. 80, the cotyledonary node being No. 1. Plantlets which
      were obtained from node 50 have been successfully transferred to the field. 

PMID- 24435306
TI  - Time-dependent effect of combination therapy with erythropoietin and granulocyte
      colony-stimulating factor in a mouse model of hypoxic-ischemic brain injury.
AB  - Erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) are likely
      to play broad roles in the brain. We investigated the effects of combination
      therapy with EPO and G-CSF in hypoxic-ischemic brain injury during the acute,
      subacute, and chronic phases. A total of 79 C57BL/6 mice with hypoxic-ischemic
      brain injury were randomly assigned acute (days 1-5), subacute (days 11-15) and
      chronic (days 28-32) groups. All of them were treated with G-CSF (250 MUg/kg) and
      EPO (5000 U/kg) or saline daily for 5 consecutive days. Behavioral assessments
      and immunohistochemistry for angiogenesis, neurogenesis, and astrogliosis were
      performed with an 8-week follow-up. Hypoxia-inducible factor-1 (HIF-1) was also
      measured by Western blot analysis. The results showed that the combination
      therapy with EPO and G-CSF in the acute phase significantly improved rotarod
      performance and forelimb-use symmetry compared to the other groups, while
      subacute EPO and G-CSF therapy exhibited a modest improvement compared with the
      chronic saline controls. The acute treatment significantly increased the density
      of CD31(+) (PECAM-1) and alpha-smooth muscle actin(+) vessels in the frontal
      cortex and striatum, increased BrdU(+)/PSA-NCAM(+) neurogenesis in the
      subventricular zone, and decreased astroglial density in the striatum.
      Furthermore, acute treatment significantly increased the HIF-1 expression in the
      cytosol and nucleus, whereas chronic treatment did not change the HIF-1
      expression, consistent with the behavioral outcomes. These results indicate that
      the induction of HIF-1 expression by combination therapy with EPO and G-CSF
      synergistically enhances not only behavioral function but also neurogenesis and
      angiogenesis while decreasing the astroglial response in a time-dependent manner.

PMID- 24435309
TI  - Part-time Residency Training in Psychiatry.
AB  - Part-time training in psychiatry has largely remained informaland has been
      utilized only by about 1% of psychiatry residents. This is puzzling considering
      the large number of women who have children during residency. In addition to
      aiding residents with child care needs, part-time training is also of potential
      value to dual-career families, handicapped residents with mobility problems,
      physicians seeking mid-career changes, and as a solution to those with funding
      problems. In this article, we present the case for systematic planning for part
      time training based on experience in our program and a survey of other programs.
      We address the practical issues of arranging inpatient and outpatient clinical
      experiences, on-call arrangements, didactic programs, funding dilemmas,
      supervision, and evaluation. 

PMID- 24435307
TI  - TUSC3 loss alters the ER stress response and accelerates prostate cancer growth
      in vivo.
AB  - Prostate cancer is the most prevalent cancer in males in developed countries.
      Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor
      suppressor gene in prostate cancer, though its function has not been
      characterized. TUSC3 shares homologies with the yeast oligosaccharyltransferase
      (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. We
      provide evidence that TUSC3 is part of the OST complex and affects N-linked
      glycosylation in mammalian cells. Loss of TUSC3 expression in DU145 and PC3
      prostate cancer cell lines leads to increased proliferation, migration and
      invasion as well as accelerated xenograft growth in a PTEN negative background.
      TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress
      response, which results in increased Akt signaling. Together, our findings
      provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in
      general and N-glycosylation in particular. 

PMID- 24435310
TI  - Residency education in administrative psychiatry : a national survey.
AB  - In 1989, the authors surveyed all general psychiatry residency programs to assess
      the availability, extent, and emphasis of administrative teaching currently being
      offered during residency training. With a return rate of 74.5%, the results
      reveal that 69.5% of the respondents presently include administrative training
      within their curricula and 56% offer didactic teaching about administrative
      issues. These results are compared with a similar survey performed 10 years
      previously in which 85% of the respondents reported offering some administrative
      training but only 39% offered didactic instruction in this area. An analysis of
      these data and a review of proposed curricula for training in administration are
      provided. 

PMID- 24435311
TI  - International medical graduates' attitudes toward substance abuse.
AB  - After developing a hypothesis that international medical graduates (IMGs)from
      different ethno-cultural backgrounds would have different attitudes toward
      substance abuse, we compared the attitudes of 79 IMG applicants to our psychiatry
      residency training program using Chappel's Substance Abuse Attitude Survey.
      Except for the finding that men were less moralistic about substance abuse than
      women, we found no significant attitudinal differences among these IMGs despite
      their diverse backgrounds. 

PMID- 24435312
TI  - Training in geriatric psychiatry.
AB  - The objective of this study was to determine the extent and the barriers to
      expansion of geriatric psychiatry training in psychiatry training programs in the
      United States. We mailed a questionnaire to the training directors of all 216
      psychiatry residency programs listed with the Accreditation Council for Graduate
      Medical Education. We received and analyzed 127 responses. Seventy-nine percent
      of the respondents reported having at least one geriatric specialist on their
      faculty, and almost half of all reported psychiatry residents take a geriatric
      rotation. Rates in other medical specialties range from 71% of internal medicine
      departments to 13% of general surgery departments with any faculty geriatric
      specialists and from 62% in family practice residents to 3% of neurology
      residents who take a geriatric rotation. Reported factors inhibiting the
      introduction of geriatrics into psychiatry residency programs include limited
      time, insufficient numbers of trained faculty, and insufficient funds. More
      direct funding supporting the research of geriatric faculty may be needed to
      stimulate the development of geriatric training. 

PMID- 24435313
TI  - The effects of sequence of clinical experience during psychiatry residency.
AB  - This article provides a preliminary report on the educational impact of
      scheduling inpatient rotations either before or after an out patient year. The
      inpatient psychiatry evaluations of a group of PGY-3 residents who had their
      inpatient training rotation after a psychodynamically focused outpatient PGY-2
      were compared with those of a group of PGY-2 residents who had their initial
      psychiatry training at the same inpatient service with the same supervisors
      during the same academic year. The PGY-3 residents had more difficulty in
      acquiring inpatient diagnostic skills, in understanding the range of inpatient
      psychopathology, in understanding the range of therapeutic interactions, and in
      development of professional psychiatric identity than PGY-2 residents on the same
      rotation. The implications of these preliminary findings for educational planning
      and future research are discussed. 

PMID- 24435314
TI  - Integration of a token economy into a child and adolescent psychiatry training
      clinic.
AB  - We developed a token economy pilot program in which reinforcers were provided by
      a university outpatient child and adolescent psychiatry clinic to address two
      problems common to psychiatry training programs: 1) psychiatric residents have
      insufficient opportunity to learn to use behavior modification techniques with
      outpatients, and 2) many patients and their parents seen in training clinics are
      poorly motivated and noncompliant with treatment, which leads to psychiatry
      resident discouragement and frustration. The rationale for the program is
      presented from the perspective of both the resident and the patient. The
      implementation of the program with 25 cases is described, including potential and
      actual difficulties. One case treated by a psychiatry resident is presented in
      more detail. 

PMID- 24435315
TI  - The ethnic/minority focus unit as a training site in transcultural psychiatry.
AB  - The ethnic/minority psychiatric inpatient units (i.e., focus units) at the
      University of California, San Francisco, train residents in transcultural
      psychiatry. This article describes the history, goals, and educational program
      that comprise this unique training experience. Two cases from the Asian Focus
      Unit illustrate how residents learn trans-cultural psychiatry during interactions
      with ethnic Asian patients and staff. Educational perspectives and current
      program evaluation are discussed. 

PMID- 24435317
TI  - Worksite choices of recent psychiatry residency graduates.

PMID- 24435318
TI  - Optimal timeline for emergency surgery in patients with strangulated groin
      hernias.
AB  - PURPOSE: This retrospective study evaluates the clinical course and outcomes of
      patients who underwent surgery for strangulated hernias. METHODS: Among 520 groin
      hernias from 2001 to 2012, 51 inguinal and 42 femoral hernias were strangulated
      and operated emergently at a tertiary referral center. Perioperative factors,
      patient profiles, and time interval to surgery (T total = time from onset to
      surgery, T 1 = time from onset to initial evaluation, T 2 = time from the first
      hospital to the tertiary center, T 3 = time from admission at the tertiary center
      to surgery, T total = T 1 + T 2 + T 3) were analyzed in patients with
      strangulation, then compared between two groups, the bowel resection (BR) group
      and the non-bowel resection (NBR) group. RESULTS: T 1, T 2 and T total in the
      bowel resection group were significantly longer than those in the non-bowel
      resection group (P < 0.05). Patients who presented initially to the tertiary
      center (T 2 = 0) had a significantly lower resection rate than patients
      transported from other hospitals (24 vs. 44 %, P = 0.048). There was no
      significant difference in morbidity between the BR and NBR groups (35 vs. 24 %, P
      = 0.231). CONCLUSIONS: The elapsed time from onset to surgery, especially T 1 and
      T 2, is the most important prognostic factor in patients with strangulated groin
      hernias. Early diagnosis and transportation are essential for good outcomes.

PMID- 24435319
TI  - RES-TOCSY: a simple approach to resolve overlapped 1H NMR spectra of enantiomers.
AB  - Chiral auxiliaries are used for the NMR spectroscopic study of enantiomers. Often
      the presence of impurities, overlap of peaks, line broadening and the
      multiplicity pattern restrict the chiral analysis in the 1D (1)H NMR spectrum.
      The present study introduces a simple 2D (1)H NMR experiment to unravel the
      overlapped spectrum. The experiment separates the spectra of enantiomers, thereby
      allowing the unambiguous assignment of all the coupled peaks and the measurement
      of enantiomeric excess (ee) from a single experiment even in combinatorial
      mixtures. 

PMID- 24435320
TI  - Frequency range extension of spectral analysis of pulse rate variability based on
      Hilbert-Huang transform.
AB  - Heart rate variability (HRV) is a well-accepted indicator for neural regulatory
      mechanisms in cardiovascular circulation. Its spectrum analysis provides the
      powerful means of observing the modulation between sympathetic and
      parasympathetic nervous system. The timescale of HRV is limited by discrete beat
      to-beat time intervals; therefore, the exploration region of frequency band of
      HRV spectrum is relatively narrow. It had been proved that pulse rate variability
      (PRV) is a surrogate measurement of HRV in most of the circumstances. Moreover,
      arterial pulse wave contains small oscillations resulting from complex regulation
      of cardiac pumping function and vascular tone at higher frequency range. This
      study proposed a novel instantaneous PRV (iPRV) measurement based on Hilbert
      Huang transform. Fifteen healthy subjects participated in this study and received
      continuous blood pressure wave recording in supine and passive head-up tilt. The
      result showed that the very-high-frequency band (0.4-0.9 Hz) varied during head
      up tilt and had strong correlation (r = 0.77) with high-frequency band and medium
      correlation (r = 0.643) with baroreflex sensitivity. The very-high-frequency band
      of iPRV helps for the exploration of non-stationary autoregulation and provides
      the non-stationary spectral evaluation of HRV without distortion or information
      loss. 

PMID- 24435321
TI  - Afatinib: a review of its use in the treatment of advanced non-small cell lung
      cancer.
AB  - Afatinib (GilotrifTM, Giotrif((r))) is an orally administered, irreversible
      inhibitor of the ErbB family of tyrosine kinases. Afatinib downregulates ErbB
      signalling by covalently binding to the kinase domains of epidermal growth factor
      receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4,
      resulting in irreversible inhibition of tyrosine kinase autophosphorylation; it
      also inhibits transphosphorylation of HER3. Afatinib is approved as monotherapy
      for the treatment of EGFR tyrosine kinase inhibitor (TKI)-naive adults with
      locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating
      EGFR mutations in the EU, and for the first-line treatment of patients with
      metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R)
      substitution mutations as detected by a US FDA-approved test in the US. In two
      randomized, open-label, multinational phase III trials, progression-free survival
      was significantly prolonged with afatinib compared with pemetrexed plus cisplatin
      (LUX-Lung 3) or gemcitabine plus cisplatin (LUX-Lung 6) in treatment-naive
      patients with advanced NSCLC with activating EGFR mutations. The objective
      response rate was significantly higher with afatinib than with pemetrexed plus
      cisplatin or gemcitabine plus cisplatin, and patient-reported outcomes for
      symptoms such as cough and dyspnoea and certain health-related quality of life
      measures significantly favoured afatinib versus pemetrexed plus cisplatin or
      gemcitabine plus cisplatin. Afatinib also showed efficacy in EGFR TKI-naive
      patients with advanced lung adenocarcinoma and activating EGFR mutations who had
      received no more than one prior chemotherapy regimen for advanced disease,
      according to the results of the noncomparative, multinational, phase II LUX-Lung
      2 trial. Oral afatinib had a manageable tolerability profile. EGFR-mediated
      adverse events (e.g. diarrhoea, rash/acne) were generally managed using dose
      reduction and delays. In conclusion, afatinib is a valuable new option for use in
      treatment-naive or EGFR TKI-naive patients with advanced lung adenocarcinoma and
      activating EGFR mutations. 

PMID- 24435322
TI  - Exenatide twice daily: a review of its use in the management of patients with
      type 2 diabetes mellitus.
AB  - Exenatide, administered subcutaneously twice daily (Byetta((r))), is a synthetic
      version of the natural peptide exendin-4, which is a glucagon-like peptide-1 (GLP
      1) receptor agonist (incretin mimetic). Exenatide binds to the GLP-1 receptor
      with the same affinity as GLP-1, but has a much longer half-life, since it is not
      degraded by the enzyme dipeptidyl peptidase-4. Exenatide twice daily enhances
      glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon
      secretion, slows gastric emptying and reduces caloric intake. In well-designed
      clinical trials, adjunctive subcutaneous exenatide 5 or 10 MUg twice daily for 16
      52 weeks significantly and dose-dependently improved glycaemic control and
      reduced mean body weight compared with placebo in patients with type 2 diabetes
      inadequately controlled with oral antihyperglycaemic drugs (OADs) and/or basal
      insulin. The improvements in glycaemic control and reductions in body weight were
      stably maintained during long-term therapy (up to 3.5 years). The efficacy of
      adjunctive exenatide twice daily was generally similar to that of basal, prandial
      or biphasic insulin, sulfonylureas, rosiglitazone and lixisenatide, and less than
      that of liraglutide, taspoglutide or exenatide once weekly with respect to
      reductions in glycated haemoglobin. Exenatide twice daily was generally well
      tolerated; mild to moderate nausea and vomiting, which decreased with time on
      therapy, were the most common adverse events. In patients not receiving
      concomitant sulfonylureas or insulin, the incidence of hypoglycaemia was low;
      when it did occur, it was generally mild in severity. Thus, adjunctive exenatide
      twice daily is a valuable option in the treatment of type 2 diabetes inadequately
      controlled with OADs and/or basal insulin. 

PMID- 24435323
TI  - Role of pregnane xenobiotic receptor in the midbrain ventral tegmental area for
      estradiol- and 3alpha,5alpha-THP-facilitated lordosis of female rats.
AB  - RATIONALE: Progesterone and its metabolite, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP), have actions in the ventral tegmental area (VTA) that are
      required for lordosis, a characteristic mating posture of female rodents. 17beta
      estradiol (estradiol) co-varies with progestogens over natural cycles, enhances
      production of 3alpha,5alpha-THP, and is required for successful reproductive
      behavior. OBJECTIVES: A question of interest is the role of pregnane xenobiotic
      receptor (PXR), a nuclear receptor that regulates enzymes needed for the
      production of 3alpha,5alpha-THP, for estradiol-mediated lordosis. The hypothesis
      tested was that if PXR is involved in estradiol-mediated biosynthesis of
      3alpha,5alpha-THP and reproductive behavior, knocking down expression of PXR in
      the VTA of estradiol-primed, but not vehicle-primed, rats should decrease
      lordosis and midbrain 3alpha,5alpha-THP; effects may be attenuated by
      3alpha,5alpha-THP administered to the VTA. METHODS: Ovariectomized rats were
      administered subcutaneous injections of oil vehicle or estradiol. Rats were then
      administered PXR antisense oligonucleotides (PXR AS-ODNs; which are expected to
      locally knock down expression of PXR), or control (saline), infusions to the VTA.
      Rats were administered 3alpha,5alpha-THP or vehicle via infusions to the VTA.
      Reproductive behavior (paced mating task) of rats was determined in addition to
      exploratory (open field), affective (elevated plus maze), and pro-social (social
      interaction task) behavior. RESULTS: Reproductive behavior (i.e., increased
      lordosis) was enhanced with estradiol-priming and infusions of 3alpha,5alpha-THP
      to the VTA. Infusions of PXR AS-ODNs to the VTA attenuated responses in estradiol
      , but not vehicle-, primed rats, compared to control infusions. CONCLUSIONS: PXR
      may be involved in a neuroregulatory response involving biosynthesis of
      3alpha,5alpha-THP in the midbrain VTA of estradiol-primed rats.

PMID- 24435324
TI  - The effects of prenatal cocaine, post-weaning housing and sex on conditioned
      place preference in adolescent rats.
AB  - RATIONALE: Gestational exposure to cocaine now affects several million people
      including adolescents and young adults. Whether prenatal drug exposures alter an
      individual's tendency to take and/or abuse drugs is still a matter of debate.
      OBJECTIVES: This study sought to answer the question "Does prenatal exposure to
      cocaine, in a dose-response fashion, alter the rewarding effects of cocaine using
      a conditioned place preference (CPP) procedure during adolescence in the rat?"
      Further, we wanted to assess the possible sex differences and the role of being
      raised in an enriched versus impoverished environment. METHODS: Virgin female
      Sprague-Dawley rats were dosed daily with cocaine at 30 mg/kg (C30), 60 mg/kg
      (C60), or vehicle intragastrically prior to mating and throughout gestation. Pups
      were culled, fostered and, on postnatal day (PND) 23, placed into isolation cages
      or enriched cages with three same-sex littermates and stimulus objects. On PND43
      47, CPP was determined across a range of cocaine doses. RESULTS: C30 exposure
      increased sensitivity to the rewarding effects of cocaine in adolescent males,
      and being raised in an enriched environment further enhanced this effect. Rats
      exposed to C60 resembled the controls in cocaine CPP. Overall, females were
      modestly affected by prenatal cocaine and enrichment. CONCLUSIONS: These data
      support the unique sensitivity of males to the effects of gestational cocaine,
      that moderate prenatal cocaine doses produce greater effects on developing reward
      circuits than high doses and that housing condition interacts with prenatal
      treatment and sex such that enrichment increases cocaine CPP mostly in adolescent
      males prenatally exposed to moderate cocaine doses.

PMID- 24435325
TI  - Association of thrombin generation potential with platelet PAR-1 regulation and P
      selectin expression in patients on dual antiplatelet therapy.
AB  - We studied the association of thrombin generation potential with platelet
      protease activated receptor (PAR)-1 regulation and platelet activation in 52
      stable coronary artery disease patients on continuous therapy with aspirin and
      clopidogrel (n = 42) or prasugrel (n = 10). Compared to controls, peak thrombin
      generation potential was elevated in only 11 patients (p > 0.05), while F1.2 was
      elevated in 26 patients (p < 0.0001). PAR-1 and thrombin inducible P-selectin
      expression were significantly elevated in patients compared to controls (p <
      0.001). There were no significant correlations between levels of thrombin
      generation potential or F1.2 and PAR-1 regulation. However, there was a
      significant inverse correlation between levels of peak thrombin generation
      potential and in vitro thrombin-inducible expression of P-selectin (p = 0.002),
      suggesting in vivo depletion of platelet alpha granules due to ongoing platelet
      activation. 

PMID- 24435326
TI  - Fabrication of porous matrix membrane (PMM) using metal-organic framework as
      green template for water treatment.
AB  - Pressure-driven membranes with high porosity can potentially be fabricated by
      removing template, such as low water stability metal-organic frameworks (MOFs) or
      other nanoparticles, in polymeric matrix. We report on the use of benign MOFs as
      green template to enhance porosity and interconnectivity of the water treatment
      membranes. Significantly enhanced separation performance was observed which might
      be attributed to the mass transfer coefficient of the substrate layer increased
      in ultrafiltration (UF) application. 

PMID- 24435327
TI  - Considerations on overcoming intrasomatic selection during mutation breeding of
      vegetatively propagated plants.
AB  - When seeds and vegetative tissues are irradiated, a competition occurs in
      meristematic tissues between lethally and sublethally affected cells on one hand
      and unaffected cells on the other hand to the advantage of the latter. This
      phenomenon was first recognized by FREISLEBEN and LEIN (1943) and termed
      intrasomatic selection by KAPLAN (1951) and diplontic selection by GAUL (1957).
      The work done on the nature of this phenomenon in seed-propagated plants is
      summarized along with suggested methods to reduce its intensity.The generally
      unencouraging results obtained so far in vegetatively propagated plants have been
      attributed to the more intensive operation of this phenomenon in this group of
      plants, consequent on the more complex nature of apical meristems and propagating
      materials. The work of ZWINTZSCHER (1959) in apples and BAUER (1957) in black
      currants have shown that it is possible to overcome its effects with suitable
      handling of irradiated materials.The radiogenetic studies done by the author in
      the potato have been reviewed in this context. Low intensity irradiation, dose
      fractionation and irradiation of physiologically dormant tubers gave higher
      survival value. The method of isolating sprouts from irradiated tubers and
      growing them, and scoring for mutations in sproutling progenies was found to
      increase mutation frequency considerably. Other methods proposed for minimizing
      the effects of intrasomatic selection in vegetatively propagated plants are
      chronic irradiation, neutron irradiation, chemical mutagenesis and lastly,
      mutagenesis of isolated single cells and growing them into whole plants. 

PMID- 24435328
TI  - [Recombination disequilibrium of independent inversions in natural populations of
      Drosophila subobscura].
AB  - Coexistence of linked independent inversions is not infrequent in natural
      populations of Drosophila subobscura. Assuming that recombination between
      independent inversions does occur at a certain rate an equilibrium stage can be
      expected at which the frequencies of the two possible trans-types A StB and AB St
      and the two possible cis-types AB and A StBSt are in balance. The theoretical
      equilibrium conditions for any given frequency of independent inversions can
      easily be calculated and compared to the observed frequency distribution of the
      four combination types of any local population. Using all available data of 13
      different populations of D. subobscura it could be found that linkage equilibrium
      is very rarely established in nature. Out of 14 independent inversion pairs 12
      showed complete or nearly complete linkage disequilibrium. In many populations
      the deviation from the equilibrium condition is highly significant. This may be
      due to selective forces acting against one or both recombination types of an
      association-dissociation group. In the many cases where the linkage
      disequilibrium is complete one of the recombination types does not occur in
      nature at all. It probably, then, has a dominant lethal or semilethal effect on
      its carriers. Another possible explanation is that recombination between
      independent inversions does not occur at all and that di equilibrium is the
      result of complete linkage. 

PMID- 24435329
TI  - [On the resistance of species of Solanum (Tuberarium) against the European Races
      of the potato nematode (Heterodera rostochiensis Woll.)].
AB  - 63 tuber bearing Solanum species of 200 proveniencies were screened for cyst
      production with race A and 11 deviating (B-) races found in Scotland, Norway, The
      Netherlands, Germany, and Switzerland. The authors thankfully acknowledge the co
      operation of A. BUMBULUCZ, J. M. DUNNETT, H. GOFFART, J. MuNSTER, L. ROER, D.
      ROTHACKER, A. SAVARY, H. STELTER and B. WEISCHER.Each race could be characterized
      by a specific host range, which was different for every race. The races are
      distinguished by their aggressivity, expressed by the aggressivity number, i.e.
      the percentage of hosts among all the hosts tested that will form cysts. The race
      Chavornay has with 13,6% the lowest aggressivity number and the race ABC with
      59,0% the highest. Solanum forms which are resistant to a race with high
      aggressivity number have the best chance to maintain this resistance against many
      races occurring in Europe.The following species are resistant to all 11 races: S.
      oplocense, S. spegazzinii (syn. S. famatinae) and S. vernei. The species S.
      sanctae-rosae EBS 1778 and P.H. 328, S. megistacrolobum EBS 1783, and S.
      tuberosum Chile EBS 2084 were tested with 6 races (the first two inclusive ABC)
      and found to be resistant to all. S. andreanum EBS 2183 and S. sparsipilum EBS
      1801 and 1890 were resistant to 5-9 races but susceptible to one.Published and
      unpublished results showed the existence of major genes in resistant species
      responsible for resistance to one as well as to several races. It therefore seems
      possible to base breeding for resistance on a few major genes only.Some hybrids,
      wild species x S. tuberosum, are used in breeding work. The reaction of these
      hybrids with the different pathotypes is reproduced in table 4. 

PMID- 24435330
TI  - Effect of temperature on pseudo-self-compatibility in Trifolium pratense L.
AB  - A relatively high temperature treatment, applied during anthesis, was shown to
      enhance self-seed production through pseudo-self-compatibility in normally self
      incompatible red clover (Trifolium pratense L.). The self-seeds were produced in
      cultures of excised stems held in 2.5 percent sucrose. The stems were excised
      when petal color was beginning to appear in the buds. During anthesis the
      cultures were incubated with the flower heads at 40  degrees  and the stems at 25
      degrees C. When most of the florets per head had opened the cultures were
      transferred to 20  degrees C and held at that temperature during the period of
      pollen growth through the styles and also during seed development. The addition
      of calcium nitrate and boric acid to the culture medium did not enhance anthesis,
      seed weight, or the number of seeds produced.Plant genotype and the environment
      provided before anthesis were the primary factors influencing the number of self
      seed produced. Although not all attempts to produce self-seed have been
      successful, with repeated trials all clones we tested produced some seed. 

PMID- 24435331
TI  - [A contribution to an evalution of general combining ability of alfalfa clones].
AB  - Recombinational performance of different clones of alfalfa was compared in two
      types of seed : (a) produced by systematic mating of the clones and (b) produced
      by the polycross procedure. No basic differences between the two types of progeny
      were found for the characteristics investigated. Thus neither greater objectivity
      nor greater test efficiency of the polycross technique was demonstrated.Factors
      determining objective evaluation of general combining ability of alfalfa by means
      of the polycross test technique are discyssed. 

PMID- 24435332
TI  - Hybridity, polyploidy and change in breeding system in a Ruellia hybrid.
AB  - Ruellia tweediana and R. tuberosa are large flowered chasmogamous diploids (n=17)
      with normal meiosis and fertility. F 1 hybrids, successful in only one direction
      (R. tweediana x R. tuberosa), are vegetatively vigorous and possess 17 often
      heteromorphic bivalents with high degree of segregational irregularities. It is
      exclusively cleistogamous and completely pollen and seed sterile. Like F 1, the
      artificial amphidiploid (n=34) is also cleistogamous but shows preferential
      chromosome pairing with complete restoration of fertility. The parental
      chromosomes are sufficiently differentiated and cleistogamy is either genie or
      due to gene-cytoplasm interaction but sterility is entirely chromosomal. All
      floral parts excepting calyx are highly deformed. Such a deformity is associated
      with sterility in the F 1 but with fertility in the amphidiploid. This is perhaps
      the first case of origin by hybridization of a true breeding and fully fertile
      cleistogamous taxon from two chasmogamous species. It also shows the extent and
      nature of change in breeding system brought about by hybridization and/or
      polyploidy.The chromosome numbers in the six, out of 16, obligate cleistogamous
      taxa (Table 4) show that they are high polyploids. Perhaps their origin has been
      in the same manner as in the present case. 

PMID- 24435333
TI  - Effects of escitalopram on serum BDNF levels in elderly patients with depression:
      a preliminary report.
AB  - BACKGROUND AND AIMS: Increasing evidence in the literature suggests a link
      between the brain-derived neurotrophic factor (BDNF) system and adult depression,
      supporting a role in the pathophysiology of the disease and response to therapy.
      Few studies have reported BDNF serum levels in elderly depressed subjects and
      their relationship with antidepressant therapy. The aim of the study was to
      evaluate BDNF serum levels in naive elderly depressed patients, before and after
      antidepressant treatment. METHODS: We enrolled n = 5 elderly naive patients
      affected by depression, according to the Diagnostic and Statistical Manual of
      Mental Disorders-IV Text Revision criteria for major depressive episode. BDNF
      serum levels were evaluated through ELISA method. Cognitive functions were
      examined by Mini Mental State Examination (MMSE) and severity of depression was
      assessed by Geriatric Depression Scale (GDS). BDNF levels were measured at
      baseline (T0) and after 2 months (T2) of escitalopram. Ten healthy elderly
      subjects were enrolled as a control group. RESULTS: The serum BDNF levels in
      patients (T0) and controls were 11.5 +/- 0.6 and 13.6 +/- 3.4 ng/ml (m +/- SD),
      respectively. At T2, the patients showed a significant improvement of depressive
      symptoms (p < 0.05), with a not significant increase of MMSE. The serum BDNF
      concentrations increased to 16.0 +/- 2.7 ng/ml at T2 (p < 0.05), beyond the
      levels of BDNF in controls. The increase in BDNF levels was significantly related
      to the improvement in GDS scores of the patients (r = 0.9, p < 0.05).
      CONCLUSIONS: Serum BDNF levels may be considered as a marker of response to
      antidepressant treatment for depression in the elderly.

PMID- 24435334
TI  - [Growth substances, metabolism of sugars and types of stems in Periploca graeca
      L].
AB  - P. graeca is a species with polymorphous stems: - short upright stems: slow
      growing and lacking revolutive movement, - long twining stems: fast growing,
      characterized by revolutive movement (=circumnutation), - long creeping stems:
      fast growing and diageotropic.The short upright-stemmed type shows evidence of
      much auxin and cytokinin activity, but no gibberellin activity can be discerned.
      Among the long-stemmed varieties less auxin and cytokinin activity is found, but
      the gibberellin activity is greater. No significant difference can be detected
      between the two long-stemmed varieties.The twining main axis of a young plant has
      a gibberellin activity which is at a maximum in the third internode from the
      apex, that is, the internode which carries the curvature responsible for the
      revolutive movement. The short upright stems are transformed to twining shoots by
      treatment with gibberellic acid.The stems of P. graeca L. contain sucrose,
      glucose and fructose in measurable quantities. The long stems have a greater
      proportion of reducing sugar and a higher invertase activity than the short
      stems.In the main axis the maximum of invertase activity and the maximum of the
      level of reducing sugars is in the third internode from the apex. The short stems
      transformed by a gibberellic acid treatment possess a high invertase activity and
      a high level of reducing sugars. These results show a relationship between the
      elongation rate, sugar metabolism and invertase activity.However, it is difficult
      to establish the relationships between peroxidase activity, auxin level and
      elongation rate on the basis of our results. 

PMID- 24435335
TI  - [Free amino acids, stem type and revolutive activity of the stems in Periploca
      graeca L].
AB  - Among the species P. graeca L. the fast-growing long types of shoots (twining and
      creeping) contain a large amount of amino acids (from 65 to 50 micromoles per
      gram of fresh weight), the dominant acid being glutamic acid. The slow growing
      short shoots have a lesser content of amino acids (30 micromoles per gram of
      fresh weight) dominated by aspartic and glutamic acids.The tips of the twining
      shoots are distinguished from those of the creeping shoots by a high proline
      level (20% of the total amino acid content against 5%). In the early development,
      when the morphological differentiation is not yet complete, twining shoots have a
      free amino acid content in which proline is abundant.The relationship between the
      high proline level and the revolutive movement is shown by the results of
      analyses of short stems made to twine by the tratment with gibberellic acid.
      Proline is abundant only in the tissues possessing the ability of circumnutation.

PMID- 24435336
TI  - Formation of p-coumaric acid and o-coumaric acid from L-phenylalanine by
      microsomal membrane fractions from potato: Evidence of membrane-bound enzyme
      complexes.
AB  - The enzymes described here are the membrane-bound L-phenylalanine ammonia-lyase
      and cinnamate hydroxylase. Microsomes prepared from tubers of Solanum tuberosum
      L. are capable of converting L-phenylalanine into both o- and p-coumaric acid.
      Three microsomal fractions obtained by density gradient centrifugation were
      characterized by their equilibrium densities. Within various subfractions we
      found different patterns of distribution of the two enzymes, probably because of
      the extent of their fixed arrangement on a membrane area. Simultaneous incubation
      of the microsomal fraction with L-[4-ring-(3)H]-phenylalanine and trans-[3
      (14)C]cinnamate indicated the existence of two pools of substrate available to
      cinnamate p-hydroxylase: cinnamate formed by the L-phenylalanine-ammonialyase
      reaction was a more effective substrate than cinnamate added to the incubation
      mixture. We conclude that the coumaric acids are formed from L-phenylalanine by a
      mechanism by which endogenously formed cinnamate is only partially equilibrated
      with exogenous cinnamate supplied in the incubation medium. This effect of enzyme
      cooperation is dependent on the integrity of membranes. The extent of cooperation
      was reduced by attempts to purify the microsomal membranes and by treatment in
      vivo with ethylene at high concentrations. 

PMID- 24435337
TI  - A sporulation-inhibiting substance from vegetative thalli of the green alga Ulva
      mutabilis, Foyn.
AB  - The formation of zoospores or gametes in the green alga Ulva mutabilis Foyn is
      shown to be blocked by some substance(s) which can be extracted into fresh growth
      medium from a suspension of living thallus fragments. The inhibiting power of
      thallus extract is greatly reduced by heat treatment, but heat-stable components
      may also be present since active extracts can be produced by boiling algal thalli
      in growth medium. Separation of the extract on a Sephadex G25 column gave two
      peaks of inhibitory activity which corresponded with the fraction's content of
      high molecular carbohydrate (probably ulvin). Various mono- and disaccharides
      were inactive. In order to block meiotic zoospore formation completely, thallus
      extracts must be applied at least 6-7 h prior to the cells' visible entry into
      the meiotic prophase. 

PMID- 24435338
TI  - [Period-lengthening and phase-shifting of the circadian rhythm of Phaseolus
      coccineus L. by theorphylline].
AB  - Under the continuous influence of theophylline the period of the circadian leaf
      movement rhythm of Phaseolus is lengthened under conditions of continuous
      darkness and under conditions of continuous light. Four-h pulses of theophylline
      shift the rhythm as a function of the phase.It is hypothesized that these
      theophylline effects are based not upon inhibition of the phosphodiesterase which
      hydrolyses 3',5'-cAMP but on the influence on membrane function, particularly the
      transport and binding of Ca(2+). 

PMID- 24435339
TI  - Stomatal closure in response to xanthoxin and abscisic acid.
AB  - The stomata of detached leaves of Commelina communis L., Hordeum vulgare L., Zea
      mays L., Vicia faba L., Phaseolus vulgaris L. and Xanthium strumarium L. closed
      when xanthoxin (XAN) was added to the transpiration stream. XAN was approximately
      half as active as (+)-abscisic acid (ABA) at an equivalent concentration. XAN,
      like ABA, sensitized stomata of Xanthium strumarium to CO2. In contrast to ABA,
      XAN was ineffective in closing stomata of isolated epidermal strips of C.
      communis or V. faba. This may be because XAN added to the transpiration stream is
      converted to ABA during passage from the xylem to the epidermis. 

PMID- 24435340
TI  - Frond development and CO2-fixation in Laminaria hyperborea.
AB  - Discs punched out of different zones of the found of Laminaria hyperborea (Gunn.)
      Fossl. were exposed to H(14)CO3 (-) in the light and in the dark for various
      lengths of time. Photosynthetic rates in young and old parts were in the same
      range, 12-39 MUmol CO2 dm(-2) h(-1) at 4 degrees C, whereas dark fixation was
      remarkably higher in the growing zone than in the old frond: 13-28% of the
      corresponding light fixation in the young phylloid and only 2-6% in the old one.
      In all parts of the frond the reductive pentose phosphate cycle is the main
      system of carboxylation, and is accompanied by a notable primary synthesis of
      amino acids. In the growing zone heavy and primary labelling of malate and
      aspartate parallel to 3-PGA is due to the undiminshed activity of the dark
      fixation system (PEP-carboxykinase) in the light. Mannitol synthesis seems to be
      enhanced with increasing age of the phylloid, but rapid and primary (14)C
      incorporation into amino acids was found in all parts of the frond.The data
      presented here suggest a possible significance of the high dark fixation rates
      for the growth of the sublittoral Laminaria hyperborea. Translocation of
      mobilized storage material from the old phylloid might supply the young tissue
      with reduced material during the growth season when the light intensity is low in
      the habitat of this alga. 

PMID- 24435341
TI  - Purification and quantitative changes of mitochondrial DNA in etiolated cucumber
      seedlings.
AB  - The mtDNA (mitochondrial DNA) extracted from etiolated seedlings of Cucumis
      sativus L. has been purified by a three-step procedure: RNase and pronase
      treatment, bio-gel filtration, analytical CsCl gradient centrifugation. This
      procedure appeared rapid, suitable for small quantities of DNA and gave highly
      reproducible results. It was used to follow the quantitative variation of the
      mtDNA in hypocotyls and cotyledons of dark-grown cucumber seedlings.The major
      feature occurring during the etiolation process appeared to be an important
      accumulation of the mtDNA in hypocotyls between 3 and 5 days of culture. The
      amount of the mtDNA per hypocotyl increased 5 times, the hypocotyl length and the
      total DNA increased 6 and 12 times respectively, between these two stages. It was
      demonstrated that at least during the first week of culture in the dark,
      endogeneous hormone-induced elongation in the cucumber hypocotyl (a non-dividing
      tissue) was associated to an important accumulation of mtDNA. 

PMID- 24435342
TI  - The metabolism of gibberellins A9, A 20 and A 29 in immature seeds of Pisum
      sativum cv. Progress No. 9.
AB  - Gibberellin A9, GA20 and GA29, all known to be endogenous to immature seeds of
      Pisum sativum cv. Progress No. 9, were fed in tritiated form to seeds of this
      cultivar cultured in vitro. [(3)H]GA9 was metabolised to [(3)H]GA20, 2beta-OH
      [(3)H]GA9, H2-[(3)H]GA31 and a H2-[(3)H]GA31 conjugate. The percentage conversion
      to each metabolite varied from feed to feed but in each instance [(3)H]GA20 was,
      at most, a minor product, suggesting that in vivo GA9 may not be the principal
      precursor of GA20. [(3)H]GA20 was converted in very high yield to [(3)H]GA29
      under conditions which suggest very strongly that this is a normal metabolic
      sequence in developing seeds of this cultivar. In addition, conjugates of
      [(3)H]GA20 and [(3)H] GA29 were formed in low yield. It was presumed that the
      latter was a metabolite of [(3)H]GA29. All metabolites, in each instance, were
      identified by combined gas chromatography-radiocounting and combined gas
      chromatography-mass spectrometry, and criteria for the unequivocal identification
      of radioactive products in feeds to plant tissues are put forward. 

PMID- 24435343
TI  - Enhancement of cell separation by colchicine in cell suspension cultures of
      soybean.
AB  - When cell suspension of soybean was cultured in the presence of colchicine
      (1.0x10(-4) to 1.0x10(-3) M), the degree of cell separation was greatly
      increased. This promotion of cell separation was accompanied with swelling of
      cells and modification of cell form. The treated suspension consisted
      predominantly of single cells and a few small aggregates, and could be repeatedly
      subcultured in the presence of 1.0x10(-4) M colchicine, but could not at 1.0x10(
      3) M. 

PMID- 24435344
TI  - The big chill : the transition from residency to managed care nightmare.
AB  - Even though concerns about managed care are a source of extraordinary distress
      among psychiatrists today, many residents are not being provided with adequate
      preparation and training to deal with those concerns. When young psychiatrists
      leave their training programs and enter practice, they are experiencing profound
      demoralization. Much of their dysphoria appears to be a result of the impact of
      specific aspects of the managed care system on the preexisting psychological
      characteristics of psychiatrists. Preventive strategies to minimize this impact
      are discussed. 

PMID- 24435345
TI  - The role of the residency training director in psychiatric recruitment.

PMID- 24435346
TI  - Gender influence on specialists' ratings of residency program candidates.
AB  - Sexism has been perceived at all levels of medical education. Although specialty
      training has been scrutinized from various perspectives, there have been few
      objective assessments of sexual discrimination in the selection of candidates.
      This study evaluates the responses of board-certified physicians to fictional
      residency applicants' personal statements, which were identical except for
      gender. Male and female physicians from six specialties in which women were
      overrepresented and six specialties in which women were underrepresented all
      favored female candidates. Female physicians in both groups rated male candidates
      as less hardworking than did male physicians. Implications of these and other
      findings are discussed. 

PMID- 24435347
TI  - Recruitment of academic psychiatrists : applicants' decision factors.
AB  - To explore factors influencing academic job seekers, the author surveyed 49
      applicants for six regular faculty positions at a university and Veterans Affairs
      (VA) medical center in Oregon. Candidates used active inquiry (40.0%) and
      advertisements (35.6%) as their pri-mary search methods, applied for an average
      of 6.75 jobs, expected the search to take 73 months, and confined their search to
      specific geographical areas (75.5%). In rank order, location, academic position,
      teaching opportunities, and research opportunities were the most appealing
      factors; VA hospital setting, fringe benefits, and administrative opportu-nities
      had the least appeal. Most applicants were moderately satisfied with current jobs
      and even more satisfied with psychiatry as a career. Related studies are
      discussed. Three of the six positions were not filled; the author discusses
      barriers to successfully recruiting academic psychiatrists. 

PMID- 24435348
TI  - Criteria for the academic promotion of medical school-based psychiatrists.
AB  - The objective of this study was to identify criteria used in recommending faculty
      for promotion in medical school-based departments of psychiatry. Chairs of 125
      departments in the United States were asked to complete a 39-item questionnaire
      on departmental demographics and the expectations for academic performance of
      tenure-track, non-tenure-track, part-time, and medical research faculty.
      Different criteria were reported for the classifications of faculty studied, but
      not for promotion of the same class of faculty to different academic ranks. The
      increasing need for faculty to generate revenue blurs the distinction between
      tenure-track and non-tenure-track faculty and calls into question whether tenure
      track can practically continue as a faculty classification. 

PMID- 24435349
TI  - Evaluating the evaluations of psychiatry residents.
AB  - This survey assessed the perceptions of psychiatry residents and faculty about
      resident evaluations. Current residents, former residents, and faculty of a
      psychiatry residency program were asked about the value and effect of feedback in
      15 specific areas and rated their preferences for evaluation methods. Residents
      and faculty most valued feedback that addressed practical clinical skills.
      Evaluations reportedly improved skills in half of the areas surveyed. Most
      respondents preferred face-to-face evaluations from individual faculty. This
      study confirms the value of resident evaluations addressing clinical skills, but
      it highlights discrepancies in expectations and merits of several methods of
      evaluation. 

PMID- 24435350
TI  - Interactive teaching, medical students, and substance abuse : university and
      community come together in a new endeavor.
AB  - The authors present an innovative approach for providing freshman and sophomore
      medical students with their initial exposure to the problems of alcohol and other
      drug abuse. Students in small interactive group seminars teach each other about
      the major areas of substance abuse: treatment, prevention/education, research,
      and law enforcement. They are aided by group moderators, by resource
      professionals, and by recovery teachers as they make field trips, attend 12-step
      meetings, and get background material. They utilize audiovisuals, role-plays, and
      programmed patients in a report/debate format. Effects of this seminar on their
      attitudes have been measured and are presented. 

PMID- 24435352
TI  - Cumulative disease activity predicts incidental hearing impairment in patients
      with rheumatoid arthritis (RA).
AB  - We previously reported that 24% of 113 rheumatoid arthritis (RA) patients had
      hearing impairment (HI). We investigated if disease activity was a predictor of
      incidental HI. One hundred and four patients completed three consecutive 6 months
      apart rheumatic evaluations and concomitant audiometric evaluations which
      included at least an interview, an otoscopic evaluation, and a pure tone
      audiometry. HI was defined if the average thresholds for at least one of low-,
      mid-, or high-frequency ranges were >=25 decibels (dB) hearing level in one or
      both ears. Appropriated statistics was used. Internal review board approval was
      obtained. Patients were most frequently middle-aged (43.4 +/- 13.3 years), female
      (89.4%), and had median disease duration of 5 years and low disease activity. All
      were receiving RA treatment. At inclusion, 24 patients had HI which was
      sensorineural in 91.7% of them. Among the 80 patients without HI at baseline, 10
      (12.5%) developed incidental HI, and they had more disease activity either at
      baseline ([median, range] disease activity score-28 joints evaluated-C-reactive
      protein [DAS28-CRP], 3.9 [1.6-7.3] vs. 2.1 [1-8.7], p = 0.006) or cumulative
      previous incidental HI (3.4 [1.8-4.8] vs. 2 [1-6.2], p = 0.007) and were more
      frequently on combined methotrexate and sulfasalazine (20 vs. 1.4%, p = 0.05)
      than their counterparts. In the adjusted Cox proportional model, cumulative DAS28
      CRP was the only variable to predict incidental HI (odds ratio, 1.8; 95%
      confidence interval, 1.1-2.7; p = 0.01). Almost 13% of RA patients with short
      disease duration and low disease activity developed incidental HI during 1 year.
      Cumulative disease activity predicted incidental HI.

PMID- 24435353
TI  - The spectrum between antiphospholipid syndrome and systemic lupus erythematosus.

PMID- 24435355
TI  - Fibromyalgia and chronic widespread pain in autoimmune thyroid disease.
AB  - Fibromyalgia and chronic widespread pain syndromes are among the commonest
      diseases seen in rheumatology practice. Despite advances in the management of
      these conditions, they remain significant causes of morbidity and disability.
      Autoimmune thyroid disease is the most prevalent autoimmune disorder, affecting
      about 10 % of the population, and is a recognized cause of fibromyalgia and
      chronic widespread pain. Recent reports are shedding light on the mechanisms of
      pain generation in autoimmune thyroid disease-associated pain syndromes including
      the role of inflammatory mediators, small-fiber polyneuropathy, and central
      sensitization. The gradual elucidation of these pain pathways is allowing the
      rational use of pharmacotherapy in the management of chronic widespread pain in
      autoimmune thyroid disease. This review looks at the current understanding of the
      prevalence of pain syndromes in autoimmune thyroid disease, their likely causes,
      present appreciation of the pathogenesis of chronic widespread pain, and how our
      knowledge can be used to find lasting and effective treatments for the pain
      syndromes associated with autoimmune thyroid disease. 

PMID- 24435356
TI  - Prospective characterization of protracted bacterial bronchitis in children.
AB  - BACKGROUND: Prior studies on protracted bacterial bronchitis (PBB) in children
      have been retrospective or based on small cohorts. As PBB shares common features
      with other pediatric conditions, further characterization is needed to improve
      diagnostic accuracy among clinicians. In this study, we aim to further delineate
      the clinical and laboratory features of PBB in a larger cohort, with a specific
      focus on concurrent viral detection. METHODS: Children with and without PBB
      (control subjects) undergoing flexible bronchoscopy were prospectively recruited.
      Basic immune function testing and lymphocyte subset analyses were performed. BAL
      specimens were processed for cellularity and microbiology. Viruses were
      identified using polymerase chain reaction (PCR) and bacteria were identified via
      culture. RESULTS: The median age of the 104 children (69% male) with PBB was 19
      months (interquartile range [IQR], 12-30 mo). Compared with control subjects,
      children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI,
      2.34-30.46). High rates of wheeze were present in both groups, and
      tracheobronchomalacia was common. Children with PBB had significantly elevated
      percentages of neutrophils in the lower airways compared with control subjects,
      and adenovirus was more likely to be detected in BAL specimens in those with PBB
      (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell
      levels in blood were elevated for age in children with PBB (0.7 * 109/L; IQR, 0.5
      0.9 cells/L). CONCLUSIONS: Children with PBB are, typically, very young boys with
      prolonged wet cough and parent-reported wheeze who have attended childcare.
      Coupled with elevated NK-cell levels, the association between adenovirus and PBB
      suggests a likely role of viruses in PBB pathogenesis.

PMID- 24435357
TI  - Double-stranded dimetallic helicates: assembling-disassembling driven by the
      Cu(I)/Cu(II) redox change and the principle of homochiral recognition.
AB  - In the presence of d(10) metal ions, prone to tetrahedral coordination, ligands
      containing two bidentate subunits will give rise to double-stranded helical
      complexes (helicates). Upon electrochemical oxidation of Cu(I) to Cu(II), the
      helicate complex tends to disassemble, thus giving rise to two mononuclear Cu(II)
      complexes with tetragonal geometry. Upon subsequent Cu(II)-to-Cu(I)
      electrochemical reduction, two Cu(I) complexes instantaneously re-assemble to
      give the helicate complex. A helicand containing a chiral subunit (e.g. 1,2
      substituted cyclohexanediamine) contains a racemic mixture of the R,R and S,S
      enantiomers. The racemic helicand, reacting with Cu(I), forms dimetallic
      helicates, in which the two strands show the same chirality, whether R,R or S,S,
      thus obeying the principle of homochiral recognition. 

PMID- 24435354
TI  - Life-threatening complications of adult-onset Still's disease.
AB  - Adult-onset Still's Disease (AOSD) since its description in 1971 has proven to be
      a very complex and challenging disease entity. This rare auto-inflammatory
      disease is classically described by the "Still's triad" of fever, rash, and
      arthritis, although the atypical cases frequently outnumber the typical ones. The
      exact pathogenesis and etiologic factors responsible for the clinical features
      remain largely obscure, despite recent suggestive cytokine biology findings.
      Diagnosis is made on clinical grounds, following the exclusion of mimickers of
      infectious, autoimmune or neoplastic etiology, with the additional consideration
      of non-specific laboratory abnormalities such as peripheral leukocytosis and
      elevation of serum ferritin and other acute phase reactants. The disease
      manifestations are protean and can include diverse complications, affecting
      multiple organ systems. Moreover, the severity of the organ involvement can vary
      considerably, representing a wide spectrum from the self-limited to severe. The
      mainstay of therapy has evolved from the traditional use of corticosteroids and
      oral immunosupressants to the newer targeted treatments with biologic agents. The
      scope of this review is to alert the clinician to the existence of life
      threatening AOSD complications, namely the macrophage activation syndrome,
      disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura,
      diffuse alveolar hemorrhage, and pulmonary arterial hypertension. Such knowledge
      may lead in earlier recognition, prompt treatment, and, ideally, improved patient
      outcomes. 

PMID- 24435359
TI  - Warren L. Butler; A tribute to a friend and fellow scientist.

PMID- 24435360
TI  - Publications of Warren L. Butler on photosynthesis.

PMID- 24435358
TI  - Use of drug-eluting stents in acute myocardial infarction with persistent ST
      segment elevation: results of the ALKK PCI-registry.
AB  - BACKGROUND: Drug-eluting stents (DES) reduce the rate of in-stent restenosis
      (ISR) and target vessel revascularization significantly when compared with bare
      metal stents (BMS). Their beneficial effects have been demonstrated in patients
      with acute myocardial infarction also, but the use of DES in the latter
      population seems to be still limited in clinical practice. METHODS AND RESULTS:
      From January 2006 to December 2011, 25,424 patients with ST-elevation myocardial
      infarction were enrolled in the German ALKK PCI-registry. In 5,467 patients (21.5
      %), a DES was implanted in the culprit segment, in 16,911 patients (66.5 %) a
      BMS, and 2,959 patients (11.6 %) received neither DES nor BMS. The rates of DES
      for typical subgroups were 31.7 % in patients with diabetes, 36.6 % in
      unprotected left main stenosis, 32.4 % in ostial lesions, 32.0 % for a stent
      length >15 mm, 26.2 % for a stent diameter <=3 mm, and 58.5 % for ISR. There was
      a wide range in the use of DES between the different ALKK hospitals with a
      minimum of 2.3 % and a maximum of 58.3 % for the total study period (median 22.0
      %, quartiles 14.6 and 37.5 %). CONCLUSIONS: Despite convincing data for the use
      of DES in patients with STEMI, there is still an underuse of DES in this clinical
      setting in Germany. This is particularly worrying for the subgroups of patients
      and lesions with a high risk of restenosis. Further efforts are needed to reduce
      the skepticism about DES and to improve guideline adherent treatment.

PMID- 24435361
TI  - The optical cross section and absolute size of a photosynthetic unit.
AB  - The concepts of a photosynthetic unit (PSU) and of an optical cross section are
      defined. The various estimates of sizes of photosynthetic units are described,
      and it is shown how an unambiguous measurement of the size of a unit can be
      obtained by measurement of its optical cross section via the saturation response
      to a single turnover light flash. The Emerson-Arnold unit must be divided by the
      quantum requirement for oxygen to obtain the true size of the unit. The size so
      obtained is the average number of chlorophylls per trap or reaction center. The
      effects of escape from open and closed traps are considered and it is shown that
      when these escape probabilities are equal, their effect on the saturation curve
      vanishes, leaving the simple cumulative one hit Poisson distribution. 

PMID- 24435362
TI  - Organization of the photosynthetic units, and onset of electron transport and
      excitation energy distribution in greening leaves.
AB  - The development and organization of the Photosynthetic units follow a step-wise
      assembly process. First the core complexes of the PSI and PSII units are formed,
      followed by their light-harvesting components; then an assembly process of these
      components into supramolecular structures takes place. Parallel to this, the
      control of excitation energy distribution between the two photosystems is
      established. This control is attributed to the modulation of the PSI unit
      effective cross section, which is possible only when LHC-I is formed and
      assembled into CPIa. Parallel to the formation of PSI and PSII, the electron
      carriers are synthesized and the electron transport chain is assembled. The
      number of PSII units operating per electron transport chain remains constant
      throughout development and equal to that of the mature chloroplast, but the
      number of PSI units per chain varies with PSII unit size. During development,
      when the rate of Chla synthesis is low, relative to the other thylakoid
      components, or is completely stopped, then the newly formed or preexisting LHC-I
      and LHC-II proteins are digested and their Chla is used for the formation of PS
      core complexes. 

PMID- 24435363
TI  - Chlorophyll-protein complexes.
AB  - Recent advances in the studies on chlorophyll-protein complexes of higher plants
      are summarized in this article. Special emphasis is laid on the isolation,
      pigment composition and the absorption and fluorescence properties of the
      complexes. 

PMID- 24435364
TI  - Relationships among cell chlorophyll content, photosystem II light-harvesting and
      the quantum yield for oxygen production in Chlorella.
AB  - Cells of the green alga Chlorella vulgaris were grown under conditions where
      total Chl/cell varied by a factor of almost 80; from 0.02 fmol/cell to nearly 1.6
      fmol/cell. The change in Chl/cell was accomplished by an approximately 11-fold
      increase in RCII/cell along with a 7-fold increase in Chl/RCII. The effective
      absorption cross section per RCII at 596 nm varied by a factor of 6, increasing
      with Chl/cell from a minimum of 20 A(2) to a maximum of 116 A(2). In contrast,
      over the same range of Chl/cell, the quantum requirement for O2 production
      remained relatively constant at 10.4+/-1.8 quanta absorbed/O2 evolved. The
      results are well described by a simple model in which changes in Chl/cell are
      produced by coordinated changes in reaction center and light-harvesting
      complexes. The model predicts that between 20 and 40% of the light-harvesting
      chlorophyll-protein complexes commonly assigned to PSII, do not function as
      antenna for PSII. 

PMID- 24435365
TI  - A consideration of the organization of chloroplast photosystem I.
AB  - Procedures that allow the fractionation of a native Photosystem I complex (PSI
      200) into several chlorophyll-containing complexes are now available. Two
      complexes, each containing ~50% of the total chlorophyll of the photosystem, can
      be isolated. One complex contains both chlorophyll a and b and serves as antenna
      complex for the reaction center while the reaction center complex contains 100
      Chl a molecules per P700 and has 7 different polypeptides. Only two of the latter
      (62 and 58 kDa) contain chlorophyll a and these can be isolated as the
      photochemically active CPI complex. Based on these fractionation methods, a model
      that describes the overall organization of the chlorophyll in Photosystem is
      presented. 

PMID- 24435366
TI  - A high molecular weight terminal pigment ("anchor polypeptide") and a minor blue
      polypeptide from phycobilisomes of the cyanobacterium Nostoc sp. (MAC): Isolation
      and characterization.
AB  - A 94 kD pigment-polypeptide, which is presumed to be involved in anchoring the
      phycobilisomes to the thylakoids, was isolated from Nostoc phycobilisomes by gel
      filtration in 63 mM formic acid. The isolation condition did not require
      detergents or denaturating reagents, as in previous procedures, and enzymatic
      degradation was not observed at the low pH of 2.5. The "anchor polypeptide" thus
      obtained had absorption (Abs) and fluorescence maxima (Em) at 658 and 673 nm,
      respectively, in 63 mM formic acid at room temperature. The maxima shifted to
      longer wavelengths in 100 mM potassium phosphate (pH 6.8), Abs 665 and Em 683 nm
      at room temperature, and Abs 665 and Em 684 nm at liquid nitrogen temperature.
      The fluorescence maxima at both temperatures correspond to the longest wavelength
      component resolved in phycobilisomes from second derivative spectra. A minor blue
      polypeptide was also found by this isolation method. The molecular weight of this
      polypeptide was ca. 18,000 and is probably similar to a polypeptide which has
      been found in the phycobilisome core of other cyanobacteria. 

PMID- 24435367
TI  - Exciton interactions in phycoerythrin.
AB  - Upon assembly of the phycoerythrin trimer into hexamer and the hexamer into
      dodecamer, marked spectral changes are observed. The absorption and circular
      dichroism spectra of the various phycoerythrin aggregates were resolved into
      Gaussian components representing individual electronic transitions of
      phycoerythrobilin chromophores within these proteins. While the contribution of a
      broad, sensitizing band (at 525 nm) is constant, with increasing aggregate size,
      a short-wavelength pair of bands centered at 555 nm decreases concomitantly with
      a dramatic increase in the intensity of a long-wavelength pair of chromophore
      transitions centered at 563 nm. The implications of these spectral changes for
      efficient energy transfer in the phycobilisome are discussed. 

PMID- 24435368
TI  - The light-harvesting chlorophyll a/b protein acts as a torque aligning
      chloroplasts in a magnetic field.
AB  - Displacement of particles from the purified light-harvesting chlorophyll a/b
      protein aggregate (LHC) was studied in magnetic fields of various strengths (0 to
      1.6 T) by polarized fluorescence measurements. Macromolecular aggregates of LHC
      have a considerable magnetic susceptibility which enables the particles to rotate
      and align with their nematic axes parallel with H. As LHC is embedded in a
      transmembrane direction thylakoids should align perpendicular to H, the mode of
      alignment experimentally observed in thylakoids. The value of the magnetic
      susceptibility could be estimated by relating it to the integral susceptibility
      of the chlorophyll molecules in LHC. The fitting of this value with the field
      strength dependency of the fluorescence polarization ratio (FP) revealed a
      relationship between the LHC content of various photosynthetic membranes and
      their capacity for alignment, which suggested that LHC might be the torque
      ordering chloroplasts in a magnetic field. 

PMID- 24435369
TI  - Relative sensitivity of various spectral forms of photosynthetic pigments to leaf
      senescence in wheat (Triticum aestivum L.).
AB  - The change in the characteristics of the absorption spectrum of chloroplasts
      which were isolated from the mature and senescing primary wheat leaves, was
      examined at various wavelengths in which the photosynthetic pigments mostly
      absorb. Chlorophyll (Chl) a was observed to be relatively more sensitive to leaf
      senescence than Chl b and carotenoids. Furthermore, the various spectral in vivo
      forms of Chl a, did not degrade to a similar extent; the far red absorbing forms
      of Chl a including species that absorb maximally at 692 nm (Chl a-692), 700 nm
      (Chl a-700) and 708 nm (Chl a 708) were found to be extremely sensitive to
      senescence induced losses. Both attached and detached senscing primary wheat
      leaves exhibited nearly similar pattern in the loss of photosynthetic pigments
      which suggests that the loss in long wavelength absorbing forms of Chl a is a
      selective indicator of leaf senescence. 

PMID- 24435370
TI  - Energy migration and exciton trapping in green plant photosynthesis.
AB  - The possible origins of the different fluorescence decay components in green
      plants are discussed in terms of a random walk and Butler's bipartite model. The
      interaction of the excitations with the photosystem II reaction centers and,
      specifically, the regeneration of theses excitations by charge recombination
      within the reaction centers, are considered. Based on comparisons between
      fluorescence decay profiles, time-dependent exciton annihilation and
      photoelectric phenomena, it appears that the fast 200 ps decay component
      corresponds to primary energy transport from the antenna to the reaction centers
      and is dominant in filling the photosystem II reaction centers. 

PMID- 24435371
TI  - Regulation of energy transfer by cations and protein phosphorylation in relation
      to thylakoid membrane organisation.
AB  - A brief review is given of the state of knowledge which indicates that the State
      I-State II transition in higher plants and green algae is due to the reversible
      phosphorylation of the chlorophyll a/b light harvesting complex. The importance
      of membrane reorganisational changes in this process is discussed in terms of
      changes in electrostatic parameters as emphasised by the interplay of the effect
      of phosphorylation and the background levels of cations surrounding the membrane.
      It is argued that recognition of this interplay is vital when using the bipartite
      or tripartite models of Butler to obtain quantitative information of energy
      transfer between the various pigment complexes. 

PMID- 24435372
TI  - Mono- bi- tri- and polypartite models in photosynthesis.
AB  - It is shown how energy fluxes in mono-bi-tri- and polypartite photosystems can be
      described. The derivation of the energy distribution term alpha and the
      probability of spill over p21 as proposed by W.L. BUTLER are reviewed. 

PMID- 24435373
TI  - Influence of thylakoid protein phosphorylation on photosynthetic electron
      transport and photophosphorylation.
AB  - Data are reported which show that thylakoid protein phosphorylation decreases
      photosystem II fluorescence yield and enhances the photosystem I dependent
      photophosphorylation catalyzed by phenazinemethosulphate in the presence of DCMU.
      The stimulation is larger at low light intensity, but is still observed at high
      intensity. These observations are interpreted to demonstrate that thylakoid
      protein phosphorylation causes a transfer of excitation energy from PS II to PS
      I, but may also have an independent stimulatory effect on PS I dependent
      photophosphorylation. 

PMID- 24435374
TI  - Energy distribution in the photochemical apparatus of Porphyridium cruentum:
      Picosecond fluorescence spectroscopy of cells in state 1 and state 2 at 77 K.
AB  - Excitation energy distribution in Porphyridium cruentum in state 1 and state 2
      was investigated by time resolved 77 K fluorescence emission spectroscopy. The
      fluorescence rise times of phycoerythrin, phycocyanin and allophycocyanin (in
      cells in state 1 and state 2) were very similar in contrast to the emission from
      chlorophyll a (Chl a) associated with the two photosystems. In state 2
      photosystem II (PSII) Chl a fluorescence emission rose faster than the PSI Chl a
      emission and decayed more rapidly, and the converse was observed in state 1.
      These kinetic data support the concept of increased energy transfer from PSII Chl
      a to PSI Chl a in state 2 in P. cruentum. 

PMID- 24435375
TI  - Analysis of Emerson enhancement under conditions where photosystem II is
      inhibited - Are the two photosystems indeed separated?
AB  - Photoacoustic measurements of photosynthetic oxygen evolution and its enhancement
      by addition of background far-red light (Emerson enhancement) were made on both
      intact and inhibited or stressed leaves. The extent of enhancement increased with
      the dehydration treatment and decreased with a mild heat treatment or with the
      addition of DCMU. It nevertheless persisted even at a very high degree of
      inhibition - a result which indicates high population ratio of single pairs of
      combined photosystem II and photosystem I units, functional in whole chain
      electron transport. This implies a restriction on the separation between
      photosystems I and II, in contrast to existing concepts. 

PMID- 24435376
TI  - Observation of enhancement and state transitions in isolated intact chloroplasts.
AB  - Enhancement of photosynthesis by supplemental photosystem 1-enriched (707nm)
      light has been investigated in intact spinach chloroplasts by the simultaneous
      measurement of the rate of oxygen evolution, yield of chlorophyll fluorescence
      and quenching of 9-aminoacridine fluorescence. Chloroplasts reducing CO2 showed a
      75% increase in the rate of O2 evolution after the addition of 707nm light,
      whereas if nitrite was used as substrate, an enhancement of only 20% was
      observed. Reduction of glycerate-3-phosphate was associated with a 40%
      enhancement by 707nm light. There appears to be a correlation between the degree
      of enhancement and the requirement for ATP in addition to reducing power.
      Prolonged illumination in 707nm light resulted in an elevation of enhancement
      whereas illumination with 650nm light caused a loss of enhancement, demonstrating
      the operation of state transitions in intact isolated chloroplasts. 

PMID- 24435377
TI  - Energy-dependent quenching of dark-level chlorophyll fluorescence in intact
      leaves.
AB  - A new type of modulation fluorometer was used in the study of energy-dependent
      chlorophyll fluorescence quenching (qE) in intact leaves. Under conditions of
      strong energization of the thylakoid membrane (high light intensity, absence of
      CO2) not only variable fluorescence, FV, but also dark-level fluorescence, FO,
      was quenched, leading to definition of a quenching coefficient, qO. Information
      on qO was shown to be essential for correct determination of photochemical (qQ)
      and energy dependent quenching (qE) by the saturation pulse method. The
      relationship between qE and qO was analysed over a range of light intensities at
      steady state conditions. qE was found to consist of two components, the second of
      which is linearly correlated with qO. qO and the second component of qE are
      interpreted to reflect the state 1 - state 2 shift caused by LHC II
      phosphorylation. 

PMID- 24435378
TI  - Mechanisms of chlorophyll fluorescence revisited: Prompt or delayed emission from
      photosystem II with closed reaction centers?
AB  - This paper proposes a model which correlates the exciton decay kinetics observed
      in picosecond fluorescence studies with the primary processes of charge
      separation in the reaction center of photosystem II. We conclude that the
      experimental results from green algae and chloroplasts from higher plants are
      inconsistent with the concept that delayed luminescence after charge
      recombination should account for the long-lived (approx. 2 ns) fluorescence decay
      component of closed photosystem II centers. Instead, we show that the
      experimental data are in agreement with a model in which the long-lived
      fluorescence is also prompt fluorescence. The model suggests furthermore that the
      rate constant of primary charge separation is regulated by the oxidation state of
      the quinone acceptor QA. 

PMID- 24435379
TI  - Evidence that the variable chlorophyll fluorescence in Chlamydomonas reinhardtii
      is not recombination luminescence.
AB  - Room temperature single photon timing measurements on intact, Chlamydomonas
      reinhardtii cells at low excitation energies have been analysed using a four
      exponential kinetic model. Closing the PSII reaction centres produced two major
      variable lifetime and two minor constant lifetime components. The yield of each
      component mirrored the changes in lifetime. Such observations indicate the
      presence of well-connected PSII centres favoring excitation energy transfer. A
      Chlamydomonas mutant lacking PSII reaction centre proteins exhibited decay
      components equivalent to those seen at FM in the wild-type. A titration of in
      vivo fluorescence, in both the mutant and wild-type algae, using DNB, produced
      decay components similar to those seen on opening PSII reaction centres. Such
      observations indicate that the luminescence hypothesis for the origin of the long
      lived lifetime component is not the case. 

PMID- 24435380
TI  - Radiationless transitions as a protection mechanism against photoinhibition in
      higher plants and a red alga.
AB  - Exposure of the red alga Porphyra perforata or leaves of Phytolacca americana and
      Echinodorus sp. to white light equivalent to full sunlight for short periods
      induced large decreases of variable fluorescence measured at 695 nm at 77K. This
      change was not produced by photoinhibition but rather appeared to result from an
      inorease in the rate constant of radiationless transition in the reaction centers
      of photosystem II. It is proposed that this increase is related to the formation
      of the high energy state which serves as a photoprotective mechanism in plants. 

PMID- 24435381
TI  - Electron donors and acceptors in photosynthetic reaction centers.
AB  - A review is given of primary and associated electron transport reactions in
      various division of photosynthetic bacteria and in the two photosystems of plant
      photosynthesis. Two types of electron acceptor chains are distinguished: type
      'Q', found in purple bacteria, Chloroflexus and system II of oxygenic
      photosynthesis and type 'F', found in green sulfur bacteria, Heliobacterium and
      photosystem I. Secondary donor reactions are discussed in relation to plant
      photosystem II. 

PMID- 24435382
TI  - Influence of magnetic fields on the P-870 triplet state in Rps. sphaeroides
      reaction centers.
AB  - Magnetic fields influence two properties of the P-870 triplet state observed in
      Rps. sphaeroides reaction centers: the yield of formation and the kinetics of
      decay. These effects have been studied in reaction centers which were prepared in
      three different states: state QA (-), state QA (2-) and state (- QA) (QA
      depleted). The triplet yields decrease with increasing magnetic fields, with
      B1/2's of about 140, 41 and 57 Gauss, respectively. The half-time of (3)P-870
      decay is not influenced by the field in state QA (-); it increases at increasing
      fields, in state QA (2-) and state (- QA), with the same B1/2 as the triplet
      yield. These results are discussed in the framework of current theories of the
      radical-pair dynamics and of the mechanism of triplet decay. 

PMID- 24435383
TI  - Photoreduction of pheophytin in photosystem II of the whole cells of green algae
      and cyanobacteria.
AB  - Photoreduction of Pheophytin 'a' (Pheo) accompanied by a decrease in the
      chlorophyll fluorescence yield is observed in photosystem II (PS II) of the whole
      cells of green algae Chlamydomonas reinhardii (a wild type and a mutant lacking
      both photosystem I and chlorophyll 'b'), Chlorella pyrenoidosa, Scenedesmus
      obliquus and cyanobacteria Phormidium laminosum, Anabaena variabilis and
      Cynechococcus elongatus under anaerobic conditions created by means of the
      glucose-glucoseoxidase-catalase. The photoreaction is activated by the addition
      of 1 MUM CCCP, inhibited by 10 MUM DCMU and reactivated upon subsequent addition
      of either ascorbate or dithionite. Oxidized NADP, benzyl viologen and methyl
      viologen accelerate dark oxidation of the reduced Pheo indicating that they are
      able to accept an electron from [Formula: see text] in PS II.The data on both
      photoreduction of Pheo in the intact cells in the absence of exogenous
      reductants, when electron donation to reaction centers of PS II occurs only from
      water, and the inhibition of this photoreaction by DCMU, show that the Pheo
      photoreduction is sensitized by the reaction centers of PS II and probably occurs
      as a result of the electron donation from the water-splitting system being in the
      state S3, to [Formula: see text] producing the long-lived state [Formula: see
      text] and O2. 

PMID- 24435385
TI  - Addendum.

PMID- 24435384
TI  - Electron transfer through photosystem II acceptors: Interaction with anions.
AB  - We present an overview of anionic interactions with the oxidation-reduction
      reactions of photosystem II (PSII) acceptors. In section 1, a framework is laid
      for the electron acceptor side of PSII: the overview begins with a current scheme
      of the electron transport pathway and of the localization of components in the
      thylakoid membrane, which is followed by a brief description of the electron
      acceptor Q or QA and the various heterogeneities associated with it. In section
      2, we review briefly the nature of the active species of the bicarbonate (HCO3 (
      )) effect, the location of the site of action of HCO3 (-), and its relationship
      to interactions with other anions. In section 3, we review data on the anion
      effects on the reoxidation of QA (-) and on the various reactions involved in the
      two-electron gate mechanism of PSII, and provide a hypothesis as to the action of
      HCO3 (-) on the protonation reactions. New data obtained by one of us (G) in
      collaboration with J.J.S. van Rensen, J.F.H Snel and W. Tonk for HCO3 (-)
      depleted thylakoids, demonstrating the abolition of the binary oscillations
      contained within the periodicity of 4 observed for proton release, are also
      reviewed. In section 4, we comment on the measured binding constant of HCO3 (-)
      at the anion binding site. And, in section 5, we review our current concept of
      the mechanism of the HCO3 (-) effect on the electron acceptor side of PSII, and
      comment on the possible physiological roles for HCO3 (-). Measurements of HCO3 (
      ) reversible anionic inhibition in intact cells of a green alga Scenedesmus are
      also reviewed. 

PMID- 24435386
TI  - Inhibitors of photosystem II and the topology of the herbicide and QB binding
      polypeptide in the thylakoid membrane.
AB  - The folding through the thylakoid membrane of the D-1 herbicide binding
      polypeptide and of the homologous D-2 subunit of photosystem II is predicted from
      comparison of amino acid sequences and hydropathy index plots with the folding of
      the subunits L and M of a bacterial photosystem. As the functional amino acids
      involved in Q and Fe binding in the bacterial photosystem of R. viridis, as
      indicated by the X-ray structure, are conserved in the homologous D-1 and D-2
      subunits of photosystem II, a detailed topology of the binding niche of QB and of
      herbicides on photosystem II is proposed. The model is supported by the observed
      amino acid changes in herbicide tolerant plants and algae. These changes are all
      in the binding domain on the matrix side of the D-1 polypeptide, and turn out to
      be of functional significance in the QB binding.New inhibitors of QB function are
      described. Their chemical structure, i.e. pyridones, quinolones, chromones and
      benzodiones, contains the features of the phenolic type herbicides. Their
      essential elements, pi-charges at particular atoms, QSAR and steric requirements
      for optimal inhibitory potency are discussed and compared with the "classical"
      herbicides of the urea/triazine type. 

PMID- 24435387
TI  - On the structure and function of cytochrome b-559.
AB  - A sumary of biochemical, biophysical, and molecular biological data is presented
      which led to the identification of two different polypeptides (alpha and beta,
      MW=9.16 and 4.27 kDa) in the cytochrome b-559 protein. The presence of a single
      His residue on each polypeptide, and the conclusion from spectroscopy that the
      heme coordination must be bis-histidine led to an obligatory requirement for
      coordination of a single heme through a heme cross-linked dimer. This structure
      does not have a precedent among soluble or membrane bound cytochromes. The
      possible participation of the cytochrome in the pathway of photoactivation is
      discussed. 

PMID- 24435388
TI  - Reverse electron flow in chloroplasts.
AB  - Energy dependent reverse electron flow reactions in isolated thylakoids provide a
      unique tool to study, in the dark, the coupling between the ATP synthase, proton
      transport and the electron transfer system. Appropriate experimental conditions
      have been established to follow experimentally the following reactions: 1. ATP
      driven proton uptake into the inner-thylakoid space, which requires preactivation
      of the ATP synthase. 2. ATP driven reverse electron transport, which involves
      proton transport as an intermediate, and results in the reduction of QA by an
      externally added electron donor. 3. ATP driven luminescence, which requires the
      presence of an oxidized partner on the water side of photosystem II, and involves
      electron transport from QB to QA. 4. DeltapH driven reverse electron flow, which
      does not require the participation of the ATP synthase, and uses reduced
      intermediates between the two photosystems as electron donors for the reduction
      of QA. 5. DeltapH driven luminescence which again uses reduced intermdiates
      between the two photosystems as electron donors for QA reduction, and requires
      the presence of an oxidized partner on the water side of photosystem II. Several
      of these reactions have been shown to occur in intact chloroplasts and may
      provide an important regulatory mechanism in vivo. 

PMID- 24435390
TI  - Endor characterization and D2O exchange in the [Formula: see text] radical in
      photosystem II.
AB  - The early suggestion by Lozier and Butler (Photochem. Photobiol. 17, 133-137
      (1973)) that EPR Signal II arises from radicals associated with the water
      splitting process in PSII has been confirmed and extended over the intervening
      years. Recent work has identified the Signal II radicals, [Formula: see text] and
      [Formula: see text], with plastosemiquinone cation species. In the experiments
      presented here we have used ENDOR spectroscopy and D2O/H2O exchange to
      characterize these paramagnets in more detail. The ENDOR matrix region, which
      arises from protons which interact weakly with the unpaired electron spin, is
      well-resolved at 4 K and at least seven resonances are apparent. A number of
      hyperfine couplings in the 3-8 MHz range are observed and are suggested to arise
      from methyl or hydroxyl protons which occur as substituents on the
      plastosemiquinone cation ring or from amino acid protons hydrogen-bonded to the
      1,4-hydroxyl groups. Orientation selection experiments are consistent with these
      possibilities. D2O/H2O exchange shows that the D(+)/Z(+) site is accessible to
      solvent. However, the exchange occurs slowly and is not complete even after 72
      hours which suggests that the free radicals are functionally isolated from
      solvent water. 

PMID- 24435389
TI  - Multidisciplinary research in photosynthesis: A case history based on the green
      alga Chlamydomonas.
AB  - This article examines the contribution of a unicellular green alga Chlamydomonas
      to progress in photosynthetic research. The objective is to focus on the aspects
      of Chlamydomonas that have provided an advantage over other photosynthetic
      organisms in investigating photosynthesis. To do this we discuss several examples
      that demonstrate the progress from a genetic study to a multidisciplinary
      approach that probes higher levels of complexity within the organism. These
      examples include the function and molecular regulation of electron transport
      components between photosystem II and photosystem I, the molecular genetics of
      the herbicide binding protein of photosystem II, and several different studies
      that have derived from a search for rubisco (ribulose-1,5-bisphosphate
      carboxylase/oxygenase) mutants in Chlamydomonas, including chloroplast ribosome
      function, the regulation of the large subunit of rubisco, and the interaction
      between photosynthetic electron transport and carbon metabolism. 

PMID- 24435391
TI  - pH dependent stabilization of S2Q A (-) and S 2Q B (-) charge pairs studied by
      thermoluminescence.
AB  - The pH dependence of emission peak temperature and decay time of
      thermoluminescence arising from S2QB (-) and S2QA (-) recombinations demonstrates
      that a stabilization of S2QB (-) occurs at low pH whereas stabilization of S2QA (
      ) occurs at high pH. Based on comparative analysis of thermoluminescence
      parameters of the two types of recombination, we suggest that in the pH range
      between 5.3 and 7.5, Em(S2/S1) and Em(QA/QA (-)) are constant, but Em(QB/QB (-))
      gradually increases with decreasing pH, while in the pH range between 7.5 and
      8.5, an unusual change occurs on S2QA (-) charge pair, which is interpreted as
      either a decrease in Em(S2/S1) or an increase in Em(QA/QA (-)). 

PMID- 24435392
TI  - pH dependent conformational changes and electrostatic effects in plastocyanin.
AB  - Reduction of plastocyanin (PC) caused a change in the electric field at the
      surface of the molecule which resulted in a 0.3 pH unit increase in the pKa of a
      nitrated derivative of Tyr 83. This change in electrical potential could alter
      the affinity for cytochrome f which is known to bind at this site. Conversely,
      properties of the copper center, including the pH dependence of the reduction
      potential, are regulated by the charge on the surface of the molecule. Both the
      reduction potential and conformation (as measured by near-UV circular dichroic
      spectra) were pH dependent. Thus the conformation and electrostatic behavior of
      PC are dependent on oxidiation state, pH and surface charge, raising the
      possibility that its redox activity is controlled by the pH gradient. 

PMID- 24435393
TI  - Stimulation and inhibition of photosystem II electron transport in cyanobacteria
      by ions interacting with the cytoplasmic face of thylakoids.
AB  - The mechanism by which suspension medium ions regulate the rate of photoinduced
      electron transport across photosystem II was investigated with ion permeabilized
      cells of the cyanobacterium Anacystis nidulans. Electron transport was measured
      as the reduction of the electroneutral acceptor dichlorophenol indophenol, whose
      surface concentration is independent of electrostatic membrane potential.
      Potassium salts stimulate photoinduced electron transport at low concentrations
      and inhibit it at higher concentrations. No inhibition is observed when an
      antichaotropic anion is associated with potassium, while the inhibition is more
      severe the stronger the chaotropic character of the anion. Neutralization of the
      surface charge by potassium ions ligated to negatively charged membrane sites at
      the cytoplasmic side is a prerequisite for the expression of the chaotropic
      inhibition of photosystem II electron transport. 

PMID- 24435394
TI  - Reaction sequences from light absorption to the cleavage of water in
      photosynthesis : Routes, rates and intermediates.
AB  - The reaction sequence between the primary electron acceptor, the oxidized
      Chlorophyll-aII, and the terminal electron donor, the water splitting enzyme
      system S, is being described in the range from nanoseconds to milliseconds. For
      the cleavage of water Chlorophyll-aII (+) extracts four electrons in four
      turnovers from the enzyme system S responsible for the water oxidation. For each
      extraction the electron is moved step by step along the chain that connects the
      Chlorophyll-aII center with that of S. Beginning with the transfer from the
      immediate donor, D1, to Chl-aII (+), the subsequent transfer from D2 to D1 (+)
      ends in the electron transfer from S to D2 (+). This final act establishes in S
      the oxidizing equivalent, probably in the form of oxidized manganese. Coupled
      with these acts is an intrinsic proton release and a surplus charge formation.
      After the generation of the 4th oxidizing equivalent in a concerted final action
      the evolution of O2 from water takes place. Correlations between the events are
      described quantitatively. 

PMID- 24435396
TI  - Characterization of a photosystem II reaction center complex isolated by exposure
      of PSII membranes to a non-ionic detergent and high concentrations of NaCl.
AB  - A highly resolved PSII reaction center complex has been prepared by exposure of
      PSII membranes to the detergent octylglucopyranoside at elevated ionic strengths;
      oxygen evolution activity is about 1,000 MUmoles O2/hr/mg Chl in the presence of
      CaCl2. A Mn quantitation and a kinetic study of Z, the donor to P680, reveals
      that on a Chl basis this new preparation shows an almost four-fold enrichment in
      Mn and the electron transport components of PSII. 

PMID- 24435395
TI  - Modification of oxygen evolving center by Tris-washing.
AB  - Tris-washing inhibits the O2-evolving center of chloroplasts and their particles
      specifically and reversibly, and it was applied to many investigations on O2
      evolving center and PS II reaction center. In this review are introduced the
      various photosynthetic investigations in which Tris-washing was applied and are
      also discussed briefly on the site and the mechanism of Tris-inactivation,
      properties of P680 and Z, characteristic change in fluorescence and delayed light
      emission, and reactivation of O2-evolving center by DCPIP.H2-treatment and photo
      reactivation of Tris-washed chloroplasts and their particles. 

PMID- 24435397
TI  - Light-dependent inactivation of photosynthetic oxygen evolution during NaCl
      treatment of photosystem II particles: The role of the 24-kDa protein.
AB  - Photosystem (PS) II particles prepared from spinach thylakoids with Triton X-100
      were treated with 1.5 M NaCl either in the light or dark. Under both conditions,
      the 24-kDa and 18-kDa proteins were released from the particles, but rebound to
      them when the NaCl concentration was reduced to 34 mM by dilution. Oxygen
      evolution measured after the dilution was inactivated following NaCl treatment in
      the light, but not following treatment in the dark. The inactivation in the light
      was suppressed when 5 mM CaCl2 was added during or after the NaCl treatment.
      Based on these observations, a scheme is proposed for the mechanism of light
      dependent inactivation of oxygen evolution during NaCl treatment of PS II
      particles and for the function of the 24-kDa protein in regulating the
      conformation of a supposed Ca(2+)-binding intrinsic protein. 

PMID- 24435398
TI  - The relation between the chloride status of the photosynthetic water splitting
      complex and the inhibitory effectiveness of amines.
AB  - The protective role of chloride ions (Cl(-)) against inhibition of the
      photosynthetic water splitting complex by amines was investigated with purified
      photosystem II membrane particles from tobacco chloroplasts. Seemingly
      competitive interactions occurred between Cl(-) (except at low concentrations)
      and Tris, but not between Cl(-) and NH3. The rate of Cl(-) release was not
      increased by the amines but, instead, may have been limited by a labilization
      under the experimental conditions of the extrinsic 23 kDa polypeptide. An
      additional detachment of the 18 kDa polypeptide was seen when SO4 (2-) ions were
      present. Tris induced changes of the thermoluminescence patterns of flash
      illuminated photosystem II particles were found to be different from those caused
      by either Cl(-) deficiency or high pH. It is concluded that the protective
      functions of Cl(-) are brough about not because it is bound to the target site of
      the inhibitory actions of Lewis bases like amines and hydroxyl ions. Instead,
      this effect of Cl(-) may be due to its influence on the tertiary and quaternary
      structures of the water oxidizing protein complex. 

PMID- 24435400
TI  - Accumulation of silver by Chromatium vinosum from solutions containing silver
      thiosulfate.
AB  - The photosynthetic sulfur bacterium, Chromatium vinosum, was cultured in
      inorganic photographic processing solutions containing silver thiosulfate complex
      salt (AgNa3(S2O3)2) under light. It was found that Chromatium was resistant to Ag
      and accumulated granular silver in the membrane during growth. The amount of Ag
      accumulated in the cells depended on the initial concentrations of the Ag salt in
      the culture solution. When the concentration of Ag was 300 mg/l, the bacteria
      accumulated Ag as high as 30% of the dry cell weight. The size of the granules
      was 0.1 to 0.3 MUm. Results from X-ray microanalysis indicated that these
      granules consisted mostly of Ag(o) with small fractions of Ag2S and AgCl. 

PMID- 24435399
TI  - Active transport in phototrophic bacteria.
AB  - Phototrophic bacteria utilize light-driven, cyclic electron flow to pump protons
      out of their cytoplasm, creating an electrochemical proton gradient, DeltaMUH+,
      outside acid and positive. These bacteria exchange external protons for internal
      cations (Na(+), K(+) and Ca(+2)), allowing the cells to maintain a nearly
      constant internal pH while maintaining the electrical component of DeltaMUH+.
      Na(+)/H(+) exchange also establishes an electrochemical Na(+) gradient.
      Phototrophic bacteria are able to utilize these electrochemical gradients as
      energy sources for the uptake of a wide variety of metabolites (e.g., sugars,
      organic acids and amino acids) via metabolite/cation symports. 

PMID- 24435401
TI  - Editorial note.

PMID- 24435403
TI  - Preface.

PMID- 24435404
TI  - Highly regioselective and chemoselective titanocene mediated Barbier-type
      allylation reactions.
AB  - Titanocene carboxylate 1 is an excellent chemoselective reagent for unprecedented
      alpha-regioselective Barbier-type reactions. It constitutes the first
      titanocene(III) able to tolerate epoxides and readily reduced carbonyl compounds,
      such as aromatic and alpha,beta-unsaturated aldehydes.

PMID- 24435406
TI  - Hypervalent iodine(III)-mediated cyclopropa(e)nation of alkenes/alkynes under
      mild conditions.
AB  - Hypervalent iodine(III)-mediated dioxygenation and diamination of alkenes have
      been previously developed. In this study, the potential application of
      hypervalent iodine(III) reagent was successfully extended to the dialkylation and
      cyclopropa(e)nation of unsaturated alkenes and alkynes. The reactions of alkenes
      with malononitrile and other active methylene compounds as the carbon
      nucleophiles give access to multisubstituted cyclopropane derivatives in moderate
      to excellent yields. Both electron-rich and electron-deficient alkenes are
      suitable substrates. Alkynes, no matter terminal or internal alkynes, work well,
      affording the corresponding highly functionalized cyclopropenes efficiently. A
      plausible mechanism of iodo(III)cyclopropanation, ring opening attack by the
      carbon-nucleophile, and recyclization was proposed for the cyclopropanation of
      trans-alkene substrates. The cyclopropenation was thought to proceed via
      iodo(III)cyclopropanation, ring-opening attack by the carbon-nucleophile,
      recyclization into a four-membered iodo(III)cyclobutene and final reductive
      elimination. The protocol might provide a complementary route to
      cyclopropanation/cyclopropenation.

PMID- 24435405
TI  - A Virtual Joy-Stick Study of Emotional Responses and Social Motivation in
      Children with Autism Spectrum Disorder.
AB  - A new virtual reality task was employed which uses preference for interpersonal
      distance to social stimuli to examine social motivation and emotion perception in
      children with Autism Spectrum Disorders. Nineteen high function children with
      higher functioning Autism Spectrum Disorder (HFASD) and 23 age, gender, and IQ
      matched children with typical development (TD) used a joy stick to position
      themselves closer or further from virtual avatars while attempting to identify
      six emotions expressed by the avatars, happiness, fear, anger, disgust, sadness,
      and surprise that were expressed at different levels of intensity. The results
      indicated that children with HFASD displayed significantly less approach behavior
      to the positive happy expression than did children with TD, who displayed
      increases in approach behavior to higher intensities of happy expressions.
      Alternatively, all groups tended to withdraw from negative emotions to the same
      extent and there were no diagnostic group differences in accuracy of recognition
      of any of the six emotions. This pattern of results is consistent with theory
      that suggests that some children with HFASD display atypical social-approach
      motivation, or sensitivity to the positive reward value of positive social
      emotional events. Conversely, there was little evidence that a tendency to
      withdraw from social-emotional stimuli, or a failure to process social emotional
      stimuli, was a component of social behavior task performance in this sample of
      children with HFASD. 

PMID- 24435407
TI  - The economic burden of skeletal-related events among elderly men with metastatic
      prostate cancer.
AB  - BACKGROUND AND OBJECTIVE: Advanced prostate cancer patients with bone metastasis
      are predisposed to skeletal complications termed skeletal-related events (SREs).
      There is limited information available on Medicare costs associated with treating
      SREs. The objective of this study was to ascertain SRE-related costs among older
      men with metastatic prostate cancer in the US. METHODS: We analysed patients aged
      66 years or older who were diagnosed with incident stage IV (M1) prostate cancer
      between 2000 and 2007 from the linked Surveillance, Epidemiology and End Results
      (SEER)-Medicare dataset. A propensity score for the incidence of an SRE was
      estimated using a logistic regression model including demographic and clinical
      baseline variables. Patients with SREs (cases) were matched to patients without
      SREs (controls) based on the propensity score, length of follow-up (i.e. date of
      prostate cancer diagnosis to last date of observation) and death. Health resource
      utilization cost differences between cases and controls over time were compared
      using generalized linear models. Healthcare costs were examined by type of SRE
      (pathological fracture only, pathological fracture with concurrent surgery,
      spinal cord compression only, spinal cord compression with concurrent surgery,
      and bone surgery only) and by source of care (inpatient, physician/non
      institutional provider, skilled nursing facility, outpatient and hospice). All
      costs were adjusted to 2009 US dollars, using the medical care component of the
      Consumer Price Index. RESULTS: Application of the inclusion criteria resulted in
      1,131 metastatic prostate cancer patients with SREs and 6,067 patients without
      SREs during follow-up. The average age of the sample was 79 years, and 14 % were
      African American. A total of 928 patients with SREs were matched to 928 patients
      without SREs. The average health care utilization cost of patients with SREs was
      US$29,696 (95 % confidence interval [CI] US$24,730-US$34,662) higher than that of
      the controls. The most expensive SRE group was spinal cord compression with
      concurrent surgery (US$82,868: 95 % CI US$67,472-US$98,264) followed by bone
      surgery only (US$37,496: 95 % CI US$29,684-US$45,308), pathological fracture with
      concurrent surgery (US$34,169: 95 % CI US$25,837-US$ 42,501), spinal cord
      compression only (US$25,793: 95 % CI US$20,933-US$30,653) and pathological
      fracture only (US$14,649: 95 % CI US$6,537-US$22,761). The largest cost
      difference by source of care was observed for hospitalizations (p < 0.01).
      CONCLUSION: Metastatic prostate cancer patients with SREs incur higher costs
      compared to similar patients without SREs. SRE costs among older stage IV (M1)
      prostate cancer patients vary by SRE type, with spinal cord compression and
      concurrent surgery costing at least twice as much as other SREs.

PMID- 24435408
TI  - Work loss in osteoarthritis.

PMID- 24435409
TI  - Performance of vertebral fracture assessment in addition to dual energy X-ray
      absorptiometry in patients with rheumatoid arthritis.

PMID- 24435410
TI  - Paediatric rheumatology in sub-Saharan Africa.

PMID- 24435412
TI  - Should children who have a cardiac arrest be treated with therapeutic
      hypothermia?

PMID- 24435411
TI  - Cost-effectiveness of a standard intervention versus a navigated intervention on
      colorectal cancer screening use in primary care.
AB  - BACKGROUND: Colorectal cancer (CRC) screening is cost-effective but underused.
      The objective of this study was to determine the cost-effectiveness of a mailed
      standard intervention (SI) and tailored navigation interventions (TNIs) to
      increase CRC screening use in the context of a randomized trial among primary
      care patients. METHODS: Participants (n = 945) were randomized either to a usual
      care control group (n = 317), to an SI group (n = 316), or to a TNI group (n =
      312). The SI group was sent both colonoscopy instructions and stool blood tests
      irrespective of baseline preference. TNI group participants were sent
      instructions for scheduling a colonoscopy, a stool blood test, or both based on
      their test preference, as determined at baseline; then, they received a
      navigation telephone call. Activity cost estimation was used to determine the
      cost of each intervention and to compute incremental cost-effectiveness ratios.
      Statistical uncertainty within the base case was assessed with 95% confidence
      intervals derived from net benefit regression analysis. The effects of uncertain
      parameters, such as the cost of planning, training, and involvement of those
      receiving "investigator salaries," were assessed with sensitivity analyses.
      RESULTS: Program costs of the SI were $167 per participant. The average cost of
      the TNI was $289 per participant. CONCLUSIONS: The TNI was more effective than
      the SI but substantially increased the cost per additional individual screened.
      Decision-makers need to consider cost structure, level of planning, and training
      required to implement these 2 intervention strategies and their willingness to
      pay for additional individuals screened to determine whether a tailored
      navigation would be justified and feasible.

PMID- 24435413
TI  - Doctors and climate change: "you played at rapid sequence induction while my
      world burned".

PMID- 24435415
TI  - Agencies condemn new Nigerian law that may deny gay people access to HIV
      services.

PMID- 24435416
TI  - GMC hearing against GP who ran out of hours was "disastrous," says judge.

PMID- 24435414
TI  - Long term duration of protective effect for HPV negative women: follow-up of
      primary HPV screening randomised controlled trial.
AB  - OBJECTIVES: To assess whether the increased sensitivity of screening for human
      papillomavirus (HPV) may represent overdiagnosis and to compare the long term
      duration of protective effect against cervical intraepithelial neoplasia grade 2
      or worse (CIN2+) in HPV based and cytology based screening. DESIGN: 13 year
      follow-up of the Swedescreen randomised controlled trial of primary HPV
      screening. SETTING: Organised cervical screening programme in Sweden.
      PARTICIPANTS: 12,527 women aged 32-38 attending organised screening were enrolled
      and randomised to HPV and cytology double testing (intervention arm, n=6257) or
      to cytology only, with samples frozen for future HPV testing (control arm,
      n=6270). MAIN OUTCOME MEASURES: Cumulative incidence of CIN2+ and CIN3+ (Kaplan
      Meier curves). Longitudinal test characteristics were calculated for cytology
      only, HPV testing only, and cytology and HPV testing combined, adjusting for
      censoring. RESULTS: The increased detection of CIN2+ in the intervention arm
      decreased over time. After six years, the cumulative incidence of CIN3+ was
      similar in both trial arms, and after 11 years the cumulative incidence of CIN2+
      became similar in both arms. The longitudinal sensitivity of cytology for CIN2+
      in the control arm at three years was similar to the sensitivity of HPV testing
      in the intervention arm at five years of follow-up: 85.94% (95% confidence
      interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV
      screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for
      cytology after three years was 92.02% (80.59% to 96.97%). CONCLUSIONS: Over long
      term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening
      and for cytology, implying that the increased sensitivity of HPV screening for
      CIN2+ reflects earlier detection rather than overdiagnosis. The low long term
      risks of CIN3+ among women who tested negative in HPV screening, support
      screening intervals of five years for such women. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00479375.

PMID- 24435417
TI  - Gene therapy for inherited blindness shows promise in first clinical trial.

PMID- 24435418
TI  - Distribution of gene frequencies under the case of random genetic drift with and
      without selection.
AB  - Studies by computer simulation to determine applicability of the theory of the
      distribution of gene frequencies at the steady state of decay to small
      populations and the effect of linkage on the distribution revealed: 1. For random
      genetic drift with no selection theory and observations agree well for
      independent assortment and linkage. 2. For random genetic drift with selection
      theory and observations agree well for independent assortment and full dominance.
      Linkage with relatively large N s decreased the mean gene frequency of unfixed
      classes and the steady rate of fixation of the favorable allele. 3. With
      independent assortment and additive gene effects agreement between theory and
      observations for the rates of fixation and loss at the terminal classes was good
      only for effective population number of at least 42. Small effective population
      numbers increased variance and decreased the steady rate of fixation and loss at
      the terminal classes. Linkage had no effect for small N s, but for relatively
      large N s, it decreased the mean of gene frequencies and increased the steady
      rate of fixation and loss at the terminal classes from that of independent
      assortment. 

PMID- 24435419
TI  - [Genetic studies on the resistance of barley to yellow rust (Puccinia striiformis
      West.)].
AB  - Five spring barley varieties resistant to race 24 of Puccinia striiformis were
      crossed with each other and with three susceptible varieties (Table 1) in almost
      all possible combinations. The F 2 generations and in two cases also the F 3,
      were inoculated in the greenhouse with race 24. F 2 generations of some of the
      crosses were, in addition, tested with race 24 in the field. Dependable
      classification of resistance and, consequently, unambiguous interpretation of
      results was possible only for the experiments carried out in the greenhouse.
      Although the field tests confirmed these results, they would not have been
      conclusive by themselves.The resistance of all of the five varieties studied is
      due to single recessive genes (Table 2). Three of the varieties have alleles at
      the same locus, the other two varieties have other resistance genes (Tables 3 and
      4): 'Bigo' - yr, 'Ab. 14' - yr, 'BBA 2890' - yr; 'Abed Binder 12' - yr2; 'I 5' -
      yr3. The results suggest that the three genes are inherited independently, close
      linkage can be excluded. 

PMID- 24435420
TI  - An unstable locus in soybeans.
AB  - Investigation of a variegated condition in the soybean variety Lincoln indicates
      instability at the Y locus. Leaf sectors of chlorophyll-less yellow tissue occur
      in distinct heritable patterns; some leaves have small flecks of yellow tissue
      (late occurring mutations) and others possess large areas or whole leaflets
      (early occurring mutations).There is evidence that this allele, Y 18 (m) ,
      mutates to the wild type, Y, which is green and stable and to the recessive, y,
      which is yellow and lethal in the seedling condition. (With an increase in the
      amount of yellow tissue there is an increase in the frequency of lethals.)
      However, changes from one type to the other are observed, and patterns of
      variegation representing different states of the instability are described. These
      depend upon the time and frequency of mutation events.Evidence is presented to
      support the hypothesis that this instability is controlled by a factor that
      resides at the locus. Such a factor governs the timing of the mutation events and
      is related to similar elements in maize, which are part of specific mutable
      systems. Control of variegation of the Y 18 (m) locus is compared with the models
      proposed for the cases of instability in maize. 

PMID- 24435421
TI  - [Competition between the male gametophytes in Oenothera under the influence of a
      gametophytic gene in the first linkage group and a model for investigations of
      branched genetic maps].
AB  - The progeny ratios obtained in male backcrosses of Oenothera hybrids to the
      complexes hookeri and flavens (identified by two marker genes and by the
      translocation break) showed statistically significant differences from Mendelian
      expectations.Presence of a gametophytic gene in the first linkage group is
      proposed. Its alleles ga (+) and ga (-) are thought to control development of the
      male gametophytes in such a manner that pollen grains carrying the different ga
      alleles and developing in a heterozygous female plant, will fertilize the female
      gamete with different average frequencies.A series of genetic models is
      developed, all taking into account the relative probability of the alleles ga (+)
      and ga (-) to function in fertilization, the probability of crossing over between
      the gene loci studied, and the branched configuration of the linkage group, due
      to the presence of the translocation.Based on these models, the relationships
      between the relative frequencies of the different classes of gametes are
      predicted for several theoretically possible arrangements of the genes within the
      linkage group.The models have general application for the localization of
      gametophytic genes and for the localization of genes in branched linkage
      groups.It turns out to be impossible to give an estimate for the disadvantage of
      ga (-) as compared to ga (+) from the backcross data alone. The empirical data
      permit only a combined estimate of the probabilities of fertilization by ga (-)
      and of crossing over between Ga and the locus of the marker gene.Comparison
      between the empirical data and the model makes it possible to determine the
      location of the marker loci and the locus of Ga with respect to one another. A
      branched linkage group appears most likely, but a linear arrangement in two
      chromosome arms cannot be ruled out.The observed cross-over values, and
      consequently, the map distances between the genes studied, are highly variable,
      both in different hybrids and in the progeny of a single hybrid. 

PMID- 24435422
TI  - Structure of populations under mixed random and sib mating.
AB  - The present investigation relates to various properties of population bred by
      mixture of breeding systems namely mixed random and sib mating. Expressions have
      been derived which give the genotypic frequencies in any given generation in
      terms of the initial values. Under the mating system considered the population
      will eventually become stable having a certain amount of heterozygosis depending
      upon the amounts of random and sib mating. The loss of heterozygosity in
      successive generations has been examined for varying amounts of sib mating in the
      population.The formulae have been derived giving the mean and genotypic variance
      in any given generation of continued mixed mating. The effect of the mating
      system considered on mean and genotypic variance in successive generations has
      been discussed in detail in case of (i) absence of dominance and (ii) complete
      dominance. 

PMID- 24435425
TI  - Pregnancy during psychiatry residency : a study of attitudes.
AB  - Fifty-eight residents at two training sites at Cornell University Medical College
      responded to our questionnaire on attitudes toward pregnant peers. Male
      respondents were more likely than female respondents to believe that pregnancy
      interfered with work performance and to anticipate personal inconvenience from a
      peer's pregnancy. When residents of each gender were asked to estimate the
      opposite gender's responses to the same questions, men more accurately
      hypothesized what their female peers would say. Women overestimated the degree of
      negative male responses and underestimated male willingness to provide special
      considerations such as schedule changes for their pregnant colleagues. 

PMID- 24435426
TI  - Psychiatry residency accreditation and measuring educational outcomes.

PMID- 24435427
TI  - Continuing education in psychotherapy as a method to attract and involve
      voluntary faculty in an academic department of psychiatry.
AB  - This article describes the development and nature of an extensive program in
      continuing education in psychotherapy for voluntary faculty, which operates
      within a division of psychotherapy. A major goal of the program is to increase
      the number and quality of psychotherapy supervisors available to train residents.

PMID- 24435428
TI  - Are we teaching psychiatrists to be ethical?
AB  - The authors conducted a nationwide survey of ethics education during psychiatry
      residency. Of the 136 program directors and 95 chief residents responding, nearly
      all agreed that ethics should be a part of the core curriculum. Program directors
      reported that most programs (60%) did offer a formal seminar series or course.
      However, 26 programs (19%) had no planned discussion of ethics in any seminar and
      fewer than 30% of all programs held seminars on the issues considered most worthy
      of formal attention, including psychiatrist-patient sexual contact,
      confidentiality, and forced treatment. The discrepancy between what program
      directors and chief residents believe should be taught and what is actually being
      taught indicates a need to focus attention on the teaching of psychiatric ethics.

PMID- 24435429
TI  - Use of a matrix in designing training experiences : experience in a rural child
      and adolescent training program.
AB  - Rural child and adolescent psychiatry residency programs offer unique training
      opportunities with a distinct and underserved population. These programs also
      face the challenge of organizing teaching resources with maximum efficiency to
      compensate for low population density, geographical isolation, and a scarcity of
      available faculty. Using a case example, the authors describe the advantages of
      combining the use of a resource matrix with a set of program-specific priorities
      to design training opportunities for residents that simultaneously meet multiple
      program objectives. Potential results of this application may include expanded
      clinical services, new research opportunities, and easier recruitment of faculty.

PMID- 24435423
TI  - From neurons to neuron neighborhoods: the rewiring of the cerebellar cortex in
      essential tremor.
AB  - Remarkably little has been written on the biology of essential tremor (ET),
      despite its high prevalence. The olivary model, first proposed in the 1970s, is
      the traditional disease model for ET; however, the model is problematic for a
      number of reasons. Recently, intensive tissue-based studies have identified a
      series of structural changes in the brains of most ET cases, and nearly all of
      the observed changes are located in the cerebellar cortex. These studies suggest
      that Purkinje cells are central to the pathogenesis of ET and may thus provide a
      focus for the development of novel therapeutic strategies. Arising from these
      studies, a new model of ET proposes that the population of Purkinje cells
      represents the site of the initial molecular/cellular events leading to ET.
      Furthermore, a number of secondary changes/remodeling observed in the molecular
      and granular layers (i.e., in the Purkinje cell "neighborhood") are likely to be
      of additional mechanistic importance. On a physiological level, the presence of
      remodeling indicates the likely formation of aberrant synapses and the creation
      of new/abnormal cortical circuits in ET. Specific efforts need to be devoted to
      understanding the cascade of biochemical and cellular events occurring in the
      Purkinje cell layer in ET and its neuron neighborhood, as well as the
      physiological effects of secondary remodeling/rewiring that are likely to be
      occurring in this brain region in ET. 

PMID- 24435431
TI  - The well-read psychiatrist.

PMID- 24435433
TI  - The control of glutamine synthetase level in Lemna minor L.
AB  - The specific activity of glutamine synthetase (E.C. 6.3.1.2) of Lemna minor L. is
      markedly reduced when either ammonium ions or glutamine are present in the growth
      medium. Combinations of 5 mM ammonia and 5 mM glutamic acid or 5 mM ammonia and 5
      mM glutamine as nitrogen source, lead to a 4-5 fold reduction of the maximum
      activity measurable on 5 mM gamma-aminobutyric acid. Analyses of the soluble pool
      of nitrogen indicate that the reduction in enzyme level is associated with an
      increase in the pool of glutamine. There is an inverse correlation between the
      apparent rate of synthesis of glutamine synthetase and the intracellular
      concentration of glutamine, and this relationship suggests that the glutamine
      synthetase of Lemna minor is subject to end product repression by the endogenous
      pool of glutamine. 

PMID- 24435434
TI  - [Studies on the fine structure of the nucleolus and the nucleolusorganizing
      region in Gnetum gnemon].
AB  - In Gnetum gnemon the nucleoli of tapetum cells and cells of the anther wall are
      made up during the interphase-stage of electron dense granules 18-20 nm in
      diameter and electron dense fibrils 8-10 nm in diameter. At the outside of the
      nucleolus or within it there can be found one to five distinct zones of low
      electron density (Fig. 1, LK). The LK is composed of +/- tightly packed fibrils 7
      8 nm in diameter. Nucleolus associated heterochromatin is never directly attached
      to the nucleolus but joined in certain cases through the LK. 

PMID- 24435432
TI  - Diffusion tensor MRI changes in gray structures of the frontal-subcortical
      circuits in amyotrophic lateral sclerosis.
AB  - In this study, we used an automated segmentation of regions of interest and co
      registration to diffusion tensor imaging (DTI) images to investigate whether
      microstructural abnormalities occur in gray structures of the frontal-subcortical
      circuits in patients with amyotrophic lateral sclerosis (ALS). Twenty-four
      patients with probable or definite sporadic ALS and 22 healthy controls were
      enrolled in the study. Thirteen out of 24 ALS patients and all of the control
      subjects underwent a detailed neuropsychological evaluation. DTI was performed to
      measure mean diffusivity (MD) and fractional anisotropy in the frontal cortex,
      caudate, putamen, globus pallidus, thalamus, amygdala and hippocampus. MD values
      of ALS patients were significantly higher in the frontal cortex (P = 0.023),
      caudate (P = 0.01), thalamus (P = 0.019), amygdala (P = 0.012) and hippocampus (P
      = 0.002) compared to controls. MD of these structures significantly correlated to
      a variable degree with neurological disability and neuropsychological
      dysfunctions. The increased MD values in several cortical and subcortical gray
      structures and their correlations with neuropsychological variables substantiate
      a multisystemic degeneration in ALS and suggest that dysfunctions of frontal
      subcortical circuits could play a pivotal role in frontal impairment and
      behavioral symptoms in ALS patients.

PMID- 24435435
TI  - Glucose metabolism of dormant and heat-activated spores of Phycomyces
      blakesleeanus burgeff.
AB  - The metabolism of [(14)C]glucose has been studied in Phycomyces spores during
      dormancy, activation, and the initial stages of germination. Dormant spores are
      able to take up and metabolize exogenous glucose into different products; the
      major part of it goes to trehalose synthesis (up to 60% when the external glucose
      concentration exceeds 10(-3) M). During activation itself (i.e. a prolonged
      treatment at 50 degrees ) there is a general increase of glucose uptake and
      metabolism, without major changes in the relative rates of (14)C-label
      distribution in the different fractions (as compared to the metabolism of dormant
      spores), except for a drop in material insoluble in 80% ethanol and a still
      higher percentage (73%) going to trehalose synthesis. In the early hours of
      germination we find an enhancement of the uptake and metabolism of glucose.
      Trehalose synthesis is practically switched off within 2 h whereas the major part
      of glucose (65%) is metabolized to CO2 and ethanol-insoluble proteinaceous
      material. 

PMID- 24435436
TI  - On the secretion of alpha-amylase by barley aleurone layers after incubation in
      gibberellic acid.
AB  - Gel filtration and centrifugation studies were used to study the distribution of
      alpha-amylase activity in homogenates of barley (Hordeum vulgare L.) aleurone
      layers. The results obtained were consistent with the hypothesis that alpha
      amylase is secreted via membrane-bound vesicles. The alpha-amylase activity in an
      homogenate of barley aleurone layers was derived not only from the enzyme
      retained in the aleurone cells but also from enzyme previously secreted from the
      cells but apparently retained by the cell walls. The amount of alpha-amylase
      retained by the cell wall was influenced by factors such as the buffer in which
      the layers were incubated or the presence of Actinomycin D in the incubation
      medium. 

PMID- 24435437
TI  - Studies on the role of abscisic acid in the initiation of bud dormancy in Alnus
      glutinosa and Betula pubescens.
AB  - The effects of leaf-applied (+-)-abscisic acid on the growth and dormancy of
      Betula pubescens Ehrh. and Alnus glutinosa Gaertn. growing under long days
      provide no evidence that leaf-applied abscisic acid induces or promotes the
      formation of resting buds in these species. Radiotracer studies show that a small
      percentage of the radioactivity applied as [2-(14)C]abscisic acid to the leaves
      accumulates in the apical region of the shoot. Of the radioactivity that was
      recovered from this region after 8 days, less than 10% was chromatographically
      similar to [2-(14)C]abscisic acid. The significance of these results with respect
      to the role of abscisic acid in regulating the induction of bud dormancy is
      discussed. 

PMID- 24435438
TI  - Simultaneous requirement of carbon dioxide and abscisic acid for stomatal closing
      in Xanthium strumarium L.
AB  - Open stomata of detached leaves of Xanthium strumarium L. closed only when carbon
      dioxide and abscisic acid (ABA) were presented simultaneously. Three parameters
      of stomatal closing were determined after additions of ABA to the irrigation
      water of detached leaves, while the leaves were exposed to various CO2
      concentrations ([CO2]s) in the air; a) the delay between addition of ABA and a
      reduction of stomatal conductance by 5%, b) the velocity of stomatal closing, and
      c) the new conductance. Changes in all three parameters showed that stomatal
      responses to ABA were enhanced by CO2; this effect followed saturation kinetics.
      Half saturation occurred at an estimated [CO2] in the stomatal pore of 200 MUl l(
      1). With respect to ABA, stomata responded in normal air with half their maximal
      amplitude at [ABA]s between 10(-6) and 10(-5) M(+-)-ABA. The amounts of ABA taken
      up by the leaves during the delay increased with a power <1 (on the average,
      0.67) of the [ABA] in the transpiration stream. The minimal amount of ABA found
      to produce a stomatal response was about 1 pmol of (+-)-ABA per cm(2) leaf area,
      almost two orders of magnitude smaller than the original content of the leaves in
      ABA indicating that most of the endogenous ABA was in a compartment isolated from
      the guard cells.An interaction between stomatal responses to CO2 and ABA was also
      found in Gossypium hirsutum L. and Commelina communis L.; it was however much
      weaker than in X. strumarium.Based on earlier findings and on the results of this
      investigation it is suggested that stomata close if the cytoplasm of the guard
      cells contains much malate and H(+). The acid content in turn is determined by
      the relative rates of production of malic acid (from endogenous as well as
      exogenous CO2) and its removal (by transport of the anion into the vacuole and
      exchange of the H(+) for K(+) with the environment of the guard cells). The
      simultaneous requirement of CO2 and ABA for stomatal closure leads to the
      inference that ABA inhibits the expulsion of H(+) from guard cells. 

PMID- 24435439
TI  - Is P-protein actin-like?-not yet.
AB  - Microfilaments associated with cytoplasmic streaming in Nitella flexilis
      internodes can be decorated with heavy meromyosin (HMM) from rabbit, both in
      vitro in cytoplasmic suspensions, and in situ in glycerinated cell segments. The
      bound HMM consists of clearly discernible, polarized arrowheads in a regular
      repeat of 360-380 A that are similar to those produced on F-actin. In contrast,
      similar arrowheads or decorations are not evident on P-protein filaments in sieve
      elements of glycerinated hypocotyl segments of Phaseolus vulgaris L. treated with
      HMM. Thus, these results contradict a recent claim that P-protein binds HMM and
      is actin-like. The mass of other evidence now available from diverse studies
      indicating that P-protein does not consist of actin or tubulin is discussed. 

PMID- 24435440
TI  - C4-Pathway photosynthesis in Portulaca oleracea and the significance of alanine
      labelling.
AB  - Portulaca oleracea L. has some features common to C4 species but it has been
      suggested from other studies that a substantial proportion of assimilated carbon
      dioxide is incorporated into pyruvate and alanine by routes not involving C4
      acids or 3-phosphoglycerate. The present paper reports that enzyme activities in
      P. oleracea leaves, and the labelling patterns observed during assimilation of
      (14)CO2, are entirely consistent with the operation of the C4 pathway, with most
      of the label appearing initially in the C-4 of C4 acids, followed by the
      prominent labelling of 3-phosphoglycerate, hexose phosphates and then sucrose and
      starch after longer periods. In contrast to other recent observations, neither
      alanine nor pyruvate was a prominent early-labelled product, and the observed
      labelling of alanine was consistent with it being derived from radioactive carbon
      initially incorporated into C4 acids. 

PMID- 24435441
TI  - The thermal conductivity of leaves.
AB  - Thermal conductivities of fresh leaves, both unmodified and infiltrated with
      water, were measured. Samples were placed between silver plates of known and
      differing temperatures, and the time required to boil off a constant volume of
      liquid was measured. The species used are evergreens: Eucalyptus globulus Labill.
      (sclerophyllous) with isolateral leaf symmetry; and Peperomia obtusifolia A.
      Dietr. (succulent), Citrus limon Burm. f. (mesophyllous), Arbutus menziessii
      Pursh. (sclerophyllous), and Heteromeles arbutifolia M. Roem. (sclerophyllous),
      all with bilateral leaf symmetry. Mean values found were in the range of 0.268 to
      0.573 W/m .  degrees C for fresh leaves, and 0.540 to 0.548 W/m .  degrees C for
      leaves infiltrated with water. An analysis of errors in the technique indicated
      that these values may be somewhat low. These results are several times higher
      than previously reported values. It is concluded that ordinary mesophytic and
      xerophytic leaves will not develop large gradients in temperature between the
      surfaces. 

PMID- 24435442
TI  - An application of gamma-scintigraphy to the observation of basipetal transport in
      moonflower.
AB  - A computer-monitored gamma-ray camera was used to observe the basipetal transport
      of (99m)Tc-pertechnetate in moonflower Ipomoea alba L. Data collected in vivo at
      1 min intervals from short, contiguous sections of stem indicated a strong
      apparent dependence of transport on water potential and are interpreted as
      supporting a turgor-driven mass-flow mechanism of translocation. 

PMID- 24435443
TI  - Future oversight of recombinant DNA research: recommendations of an Institute of
      Medicine committee.

PMID- 24435444
TI  - Resveratrol inhibits BMP-4-stimulated VEGF synthesis in osteoblasts: suppression
      of S6 kinase.
AB  - Resveratrol is well known as a natural polyphenol abundantly found in red wine.
      We previously reported that bone morphogenetic protein-4 (BMP-4) stimulates
      vascular endothelial growth factor (VEGF) synthesis via p70 S6 kinase in
      osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect
      of resveratrol on the BMP-4-stimulated VEGF synthesis in MC3T3-E1 cells.
      Resveratrol significantly suppressed BMP-4-stimulated release and expression
      levels of VEGF mRNA. SRT1720, an activator of SIRT1 with potencies greater than
      resveratrol, also reduced VEGF release and the mRNA levels. Both resveratrol and
      SRT1720 markedly attenuated the BMP-4-induced phosphorylation of p70 S6 kinase
      without affecting the BMP-4-induced phosphorylation of Smad1/5/8. These findings
      strongly suggest that resveratrol attenuates BMP-4-stimulated VEGF synthesis
      through suppression of the activation of p70 S6 kinase in osteoblasts, and that
      the inhibitory effect is mediated at least in part by SIRT1 activation.

PMID- 24435445
TI  - Targeting microtubules by natural agents for cancer therapy.
AB  - Natural compounds that target microtubules and disrupt the normal function of the
      mitotic spindle have proven to be one of the best classes of cancer
      chemotherapeutic drugs available in clinics to date. There is increasing evidence
      showing that even minor alteration of microtubule dynamics can engage the spindle
      checkpoint, arresting cell-cycle progression at mitosis and subsequently leading
      to cell death. Our improved understanding of tumor biology and our continued
      appreciation for what the microtubule targeting agents (MTAs) can do have helped
      pave the way for a new era in the treatment of cancer. The effectiveness of these
      agents for cancer therapy has been impaired, however, by various side effects and
      drug resistance. Several new MTAs have shown potent activity against the
      proliferation of various cancer cells, including resistance to the existing MTAs.
      Sustained investigation of the mechanisms of action of MTAs, development and
      discovery of new drugs, and exploring new treatment strategies that reduce side
      effects and circumvent drug resistance could provide more effective therapeutic
      options for patients with cancer. This review focuses on the successful cancer
      chemotherapy from natural compounds in clinical settings and the challenges that
      may abort their usefulness.

PMID- 24435446
TI  - Highly active combination of BRD4 antagonist and histone deacetylase inhibitor
      against human acute myelogenous leukemia cells.
AB  - The bromodomain and extra-terminal (BET) protein family members, including BRD4,
      bind to acetylated lysines on histones and regulate the expression of important
      oncogenes, for example, c-MYC and BCL2. Here, we demonstrate the sensitizing
      effects of the histone hyperacetylation-inducing pan-histone deacetylase (HDAC)
      inhibitor panobinostat on human acute myelogenous leukemia (AML) blast progenitor
      cells (BPC) to the BET protein antagonist JQ1. Treatment with JQ1, but not its
      inactive enantiomer (R-JQ1), was highly lethal against AML BPCs expressing mutant
      NPM1c+ with or without coexpression of FLT3-ITD or AML expressing mixed lineage
      leukemia fusion oncoprotein. JQ1 treatment reduced binding of BRD4 and RNA
      polymerase II to the DNA of c-MYC and BCL2 and reduced their levels in the AML
      cells. Cotreatment with JQ1 and the HDAC inhibitor panobinostat synergistically
      induced apoptosis of the AML BPCs, but not of normal CD34(+) hematopoietic
      progenitor cells. This was associated with greater attenuation of c-MYC and BCL2,
      while increasing p21, BIM, and cleaved PARP levels in the AML BPCs. Cotreatment
      with JQ1 and panobinostat significantly improved the survival of the NOD/SCID
      mice engrafted with OCI-AML3 or MOLM13 cells (P < 0.01). These findings highlight
      cotreatment with a BRD4 antagonist and an HDAC inhibitor as a potentially
      efficacious therapy of AML.

PMID- 24435447
TI  - Mutant ras elevates dependence on serum lipids and creates a synthetic lethality
      for rapamycin.
AB  - The conversion of normal cells to cancer cells involves a shift from catabolic to
      anabolic metabolism involving increased glucose uptake and the diversion of
      glycolytic intermediates into nucleotides, amino acids, and lipids needed for
      cell growth. An underappreciated aspect of nutrient uptake is the utilization of
      serum lipids. We investigated the dependence of human cancer cells on serum
      lipids and report here that Ras-driven human cancer cells are uniquely dependent
      on serum lipids for both proliferation and survival. Removal of serum lipids also
      sensitizes Ras-driven cancer cells to rapamycin-indicating that the enhanced need
      for serum lipids creates a synthetic lethal phenotype that could be exploited
      therapeutically. Although depriving humans of serum lipids is not practical,
      suppressing uptake of lipids is possible. Suppressing macropinocytosis in Ras
      driven cancer cells also created sensitivity to suppression of the
      mammalian/mechanistic target of rapamycin complex 1 (mTORC1). It is speculated
      that this property displayed by Ras-driven cancer cells represents an Achilles'
      heel for the large number of human cancers that are driven by activating Ras
      mutations.

PMID- 24435448
TI  - Enhancement of the tumor penetration of monoclonal antibody by fusion of a
      neuropilin-targeting peptide improves the antitumor efficacy.
AB  - The limited localization and penetration of monoclonal antibodies (mAb) into
      solid tumors restricts their antitumor efficacy. Here, we describe a solid tumor
      targeting antibody with enhanced tumor penetration activity. We designed a 22
      residue peptide (A22p), which was extracted from the C-terminal basic region of
      semaphorin 3A (Sema3A) but modified to have higher affinity with neuropilin
      receptors (NRP), and genetically fused it to the C-terminus of Fc of human
      immunoglobulin G1 via a 15-residue (G4S)3 linker, generating Fc-A22p, for the
      bivalent binding to NRPs. In contrast to Fc or the monovalent A22p peptide alone,
      Fc-A22p homed to tumor vessels and induced vascular permeability through VE
      cadherin downregulation and penetrated tumor tissues by interacting with NRPs in
      mice bearing human tumor xenografts. We extended the Fc-A22p platform by
      generating mAb-A22p antibodies of two clinically approved solid tumor-targeting
      mAbs, the anti-EGF receptor mAb cetuximab (erbitux), and the anti-Her2 mAb
      trastuzumab (herceptin). The mAb-A22p antibodies retained the intrinsic antigen
      binding, natural Fc-like biophysical properties, and productivity in mammalian
      cell cultures, comparable with those of the parent mAbs. In mouse xenograft tumor
      models, the mAb-A22p antibodies more efficiently homed to tumor vessels and
      spread into the extravascular tumor parenchyma, which significantly enhanced
      antitumor efficacy compared with the parent mAbs. Our results suggest that mAb
      A22p is a superior format for solid tumor-targeting antibodies due to its
      enhanced tumor tissue penetration and greater antitumor efficacy compared with
      conventional mAbs.

PMID- 24435450
TI  - Removal of uranium(VI) from aqueous solution using iminodiacetic acid derivative
      functionalized SBA-15 as adsorbents.
AB  - Three different functional SBA-15 were prepared by a post-grafting method using
      three iminodiacetic acid derivatives of ethylenediaminetriacetic acid (ED3A),
      diethylenetriaminetetraacetic acid (DT4A), and 1,2
      cyclohexylenedinitrilotriacetic acid (CyD3A), which were used as adsorbents for
      removal of uranium(vi) from aqueous solution. These materials were characterized
      by FT-IR, NMR, TEM, nitrogen adsorption/desorption experiments, and elemental
      analysis. The effect of pH, ionic strength, contact time, solid-liquid ratio,
      initial metal ion concentration, temperature, and coexisting ions on uranium(vi)
      sorption behaviors of the functionalized SBA-15 was studied. Typical sorption
      isotherms (Langmuir and Freundlich) were determined for the sorption process, and
      the maximum sorption capacity was calculated. The influence of functional groups
      on uranium(vi) sorption was also discussed. As a result, compared with other
      current U(vi) sorbents (granite, kaolin, attapulgite), SBA-15-1,2
      cyclohexylenedinitrilotriacetic acid (SBA-15-CyD3A) possessed good selective
      sorption properties, which had potential application in separation of
      uranium(vi). 

PMID- 24435451
TI  - From ruthenium olefin metathesis catalyst to (eta5-3-phenylindenyl)hydrido
      complex via alcoholysis.
AB  - The synthesis and characterisation of [Ru(H)(eta(5)-3-phenylindenyl)((i)Bu
      Phoban)2] 4 is reported ((i)Bu-Phoban = 9-isobutyl-9-phosphabicyclo-[3.3.1]
      nonane). 4 is obtained via alcoholysis of metathesis pre-catalyst M11, in a
      process that was previously thought to be limited to analogous complex
      [RuCl2(PPh3)2(3-phenylindenylidene)] (M10). 

PMID- 24435449
TI  - Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain
      and extra-terminal (BET) bromodomain protein BRD2.
AB  - The transcription factor signal STAT5 is constitutively activated in a wide range
      of leukemias and lymphomas, and drives the expression of genes necessary for
      proliferation, survival, and self-renewal. Thus, targeting STAT5 is an appealing
      therapeutic strategy for hematologic malignancies. Given the importance of
      bromodomain-containing proteins in transcriptional regulation, we considered the
      hypothesis that a pharmacologic bromodomain inhibitor could inhibit STAT5
      dependent gene expression. We found that the small-molecule bromodomain and extra
      terminal (BET) bromodomain inhibitor JQ1 decreases STAT5-dependent (but not STAT3
      dependent) transcription of both heterologous reporter genes and endogenous STAT5
      target genes. JQ1 reduces STAT5 function in leukemia and lymphoma cells with
      constitutive STAT5 activation, or inducibly activated by cytokine stimulation.
      Among the BET bromodomain subfamily of proteins, it seems that BRD2 is the
      critical mediator for STAT5 activity. In experimental models of acute T-cell
      lymphoblastic leukemias, where activated STAT5 contributes to leukemia cell
      survival, Brd2 knockdown or JQ1 treatment shows strong synergy with tyrosine
      kinase inhibitors (TKI) in inducing apoptosis in leukemia cells. In contrast,
      mononuclear cells isolated form umbilical cord blood, which is enriched in normal
      hematopoietic precursor cells, were unaffected by these combinations. These
      findings indicate a unique functional association between BRD2 and STAT5, and
      suggest that combinations of JQ1 and TKIs may be an important rational strategy
      for treating leukemias and lymphomas driven by constitutive STAT5 activation.

PMID- 24435452
TI  - Plasminogen activator inhibitor-1 -675 4G/5G polymorphism and polycystic ovary
      syndrome risk: a meta analysis.
AB  - PURPOSE: Several studies have reported that excessive amounts of plasminogen
      activator inhibitor-1(PAI-1) might increase the incidence of polycystic ovary
      syndrome(PCOS), but so far the published results were inconsistent. The aim of
      this study was to further investigate the association between PAI-1 gene
      polymorphism and the susceptibility to PCOS by performing a meta-analysis.
      METHODS: A comprehensive literature search for relevant studies was conducted on
      google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and
      the Chinese Biomedical Literature Database (CBM). This meta-analysis was
      performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95%
      confidence interval (CI) was calculated. RESULTS: Ten case-control studies were
      included in this meta-analysis with a total of 2,079 cases and 1,556 controls.
      The results showed that PAI-1 -675 4G/5G polymorphism may increase the risk of
      PCOS, especially among Asian populations. However, there was no statistically
      significant association between the polymorphism and PCOS risk in Caucasians.
      CONCLUSION: Our meta-analysis suggests that PAI-1 -675 4G/5G polymorphism may
      contribute to increasing susceptibility to PCOS in Asians. Detection of the PAI-1
      gene polymorphism might be a promising biomarker for the susceptibility of PCOS.

PMID- 24435453
TI  - Fertility preservation: moving ahead faster than expected!

PMID- 24435454
TI  - Could empirical low-dose-aspirin administration during IVF cycle affect both the
      oocytes and embryos quality via COX 1-2 activity inhibition?
AB  - PURPOSE: To compare qualitative and quantitative ovarian response in idiopathic
      infertile women treated with low-dose-aspirin (LDA) during in-vitro-fertilization
      (IVF) cycles (pl) versus untreated ones. METHODS: We conducted an observational
      cohort-study on normo-responders patients aged between 25 and 45,years referred
      to Assisted-Reproductive Unit --University of Padua--in order to evaluate the
      ovarian response effects (both qualitative and quantitative) after LDA
      administration. In detail we aim to assess if LDA administration could improve
      ovarian response, reducing the gonadotropin administration, and if its
      administration could increase the amount of follicles greater than 16 mm at pick
      up, the amount and quality of oocytes retrieved, the amount and quality of
      embryos, the chance to achieve a pregnancy and to carry it on. RESULTS: One
      hundred six LDA-treated patients (Group-A) and 100 not-treated ones (Group-B)
      were homogeneous for age and BMI. The Group-A, compared to Group-B, showed higher
      gonadotropin request, higher number of ovarian follicles at pick-up, more
      follicles bigger than 16 mm in diameter and more retrieved oocytes (despite
      higher number of immature and at germinal vesicle stage oocytes) but lower
      quality of obtained embryos. The comparison between two Groups in term of
      retrieved oocytes /number of follicles, mature oocytes/retrieved oocytes,
      fertilized oocytes/mature oocytes and good embryos quality/mature oocytes showed
      a strongly advantageous ratio for Group-B. For each considered outcome, we found
      a dose-related effect. CONCLUSIONS: It is mandatory to define which patients
      could benefit from LDA administration and the adequate timing to administer it
      since the empirical administration could negatively affect both oocyte and embryo
      quality during IVF cycles.

PMID- 24435455
TI  - Does the presence of coronary artery disease impact perioperative outcomes
      following partial hepatectomy?
AB  - INTRODUCTION: Coronary artery disease (CAD) is often considered a
      contraindication to hepatectomy despite a lack of data to support this practice.
      The purpose of this study is to evaluate the impact of CAD on postoperative
      outcomes in patients undergoing hepatectomy. MATERIAL AND METHODS: A total of
      1,206 consecutive patients undergoing hepatectomy from August 1995 to June 2009
      were included. Propensity matching was performed to identify differences in
      morbidity and mortality between patients with and without CAD. Subgroup analyses
      were performed to stratify patients based on the severity of CAD and the interval
      between coronary intervention and hepatectomy. RESULTS: Of all patients, 138
      (11.4%) had a diagnosis of CAD and were more likely to have a malignant diagnosis
      and other comorbid conditions including renal insufficiency, COPD, and diabetes.
      Matched patients with CAD had no significant differences in complication rates,
      with 2.2 and 5.8% of CAD patients experiencing a postoperative myocardial
      infarction or arrhythmia, respectively. Propensity matching failed to identify
      differences in mortality or morbidity. Subgroup analysis revealed similar rates
      of mortality and complications regardless of the severity of CAD or the time
      interval between coronary intervention and hepatectomy. CONCLUSION: Despite the
      increased prevalence of major medical comorbidities, selected patients with CAD
      can safely undergo hepatectomy with acceptable rates of postoperative morbidity
      and mortality.

PMID- 24435456
TI  - Is a drain necessary routinely after laparoscopic cholecystectomy for an acutely
      inflamed gallbladder? A retrospective analysis of 457 cases.
AB  - BACKGROUND: During laparoscopic surgery for an acutely inflamed gallbladder, most
      surgeons routinely insert a drain. However, no consensus has been reached
      regarding the need for drainage in these cases, and the use of a drain remains
      controversial. METHODS: This retrospective study divided 457 cases into two
      groups according to whether or not a drain was inserted and reviewed the surgical
      outcomes and perioperative morbidity. RESULTS: In this study, 231 patients had no
      drains and 226 had drains. Both groups were comparable in terms of pathology,
      demographics, and operative details. There was no statistical difference in
      operating time, visual analog scale for pain, or postoperative hospital stay.
      Morbidity occurred in 49 cases (10.7%) and did not differ significantly between
      the two groups. No mortality occurred in this study. CONCLUSIONS: The routine use
      of a drain after laparoscopic cholecystectomy for an acutely inflamed gallbladder
      had no effect on the postoperative morbidity. Therefore, this retrospective study
      supports that it is feasible not to insert a drain routinely in laparoscopic
      cholecystectomy for patients who have an acutely inflamed gallbladder.

PMID- 24435457
TI  - Can cantilever transforaminal lumbar interbody fusion (C-TLIF) maintain segmental
      lordosis for degenerative spondylolisthesis on a long-term basis?
AB  - PURPOSE: To determine if cantilever transforaminal lumbar interbody fusion (C
      TLIF) using the crescent-shaped titanium interbody spacer (IBS) favors
      acquisition of segmental and lumbar lordosis even for degenerative
      spondylolisthesis (DS) on a long-term basis. METHODS: We analyzed 23 consecutive
      patients who underwent C-TLIF with pedicle screw instrumentations fixed with
      compression for a single-level DS. Measurements on the lateral radiographs taken
      preoperatively, 2 weeks postoperatively and at final follow-up included disc
      angle (DA), segmental angle (SA), lumbar lordosis (LL), disc height (%DH) and
      slip rate (%slip). RESULTS: There was a good functional recovery with 100 %
      fusion rate at the mean follow-up of 62 months. Segmental lordosis (DA and SA)
      and %DH initially increased, but subsequently decreased with the subsidence of
      the interbody spacer, resulting in a significant increase (p = 0.046) only in SA
      from 13.2 degrees  +/- 5.5 degrees  preoperatively to 14.7 degrees  +/- 6.4
      degrees  at the final follow-up. Changes of LL and %slip were more consistent
      without correction loss finally showing an increase of LL by 3.6 degrees  (p =
      0.005) and a slip reduction by 6.7 % (p < 0.001). CONCLUSIONS: Despite the
      inherent limitation of placing the IBS against the anterior endplate of the upper
      vertebra in the presence of DS, the C-TLIF helped significantly restore segmental
      as well as lumbar lordosis on a long-term basis, which would be of benefit in
      preventing hypolordosis-induced back pain and the adjacent level disc disease.

PMID- 24435458
TI  - The transmembrane distribution of galactolipids in chloroplast thylakoids is
      universal in a wide variety of temperate climate plants.
AB  - The transmembrane distribution of monogalactosyldiacylglycerol and
      digalactosyldiacylglycerol was determined in chloroplast thylakoids from a range
      of temperate climate plants. These plants included dicotyledons, monocotyledons,
      C16:3 and C18:3 plants and herbicide-resistant species. In all the thylakoids
      examined monogalactosyldiacylglycerol was enriched in the outer leaflet (53-65%)
      while digalactosyldiacylglycerol was highly enriched in the inner leaflet (78
      90%). The non-bilayer forming monogalactosyldiacylglycerol represented 55-81% of
      the total acyl lipids of the outer monolayer. The relative acyl lipid composition
      of both leaflets of the thylakoid membrane indicates that the lamellar structure
      is strongly favored in the inner monolayer, whereas the outer one presents a
      metastable character which allows the probable coexistence of both lamellar and
      non-lamellar phases. The consequence of this asymmetry for the stability and
      function of the thylakoid membrane is discussed. 

PMID- 24435459
TI  - Dependence of energization of thylakoids on frequency of exciting flashes in
      intact chloroplasts.
AB  - We investigated the frequency-dependence of the flash-induced electrochromic
      absorbance change, DeltaA515, and of the pH-indicating absorbance change of
      neutral red in isolated intact chloroplasts. The energization pattern of
      thylakoids depended strongly on the frequency (f) of the exciting flashes, tested
      between 0.05 and 2 s(-1). When the frequency was increased from 0.1 to 1 s(-1)
      the total initial change and the slow rise of DeltaA515 decreased by about 30%
      and 70%, respectively, and both the slow rise and decay were considerably
      accelerated. These changes were fully reversible, even after prolonged excitation
      at 1 s(-1), if the frequency was decreased again to 0.1 s(-1). Accumulation of an
      appreciable transmembrane electric field strength could not be detected in any of
      our experiments, at high frequency, since the decay of DeltaA515 was considerably
      accelerated when the frequency was increased. In contrast, DeltapH significantly
      increased at higher frequencies of the exciting flashes. In the steady-state
      (after about 100 flashes) DeltapH was about 0.5-0.8 pH unit higher than in the
      dark or at low frequencies. In the presence of nigericin or dithionite, both of
      which prevented accumulation of protons in the lumen, the total initial change in
      DeltaA515 at f=1 s(-1) relative to that at f=0.1 s(-1) decreased to a similar
      extent as in the control. The proportion of the slow rise relative to the initial
      amplitude, however, did not decrease. Our data support the suggestion that
      DeltapH controls the amplitude of the slow rise of DeltaA515. However, contrary
      to a previous statement (B. Bouges-Bouquet (1981) Biochim. Biophys. Acta 535, 327
      340), we show that the DeltapH effect cannot be accounted for by variation of the
      rate of this kinetic component of DeltaA515. 

PMID- 24435460
TI  - Effect of heptane-extraction on the stability of subunit organization of
      photosystem I reaction center complexes.
AB  - Treatment of lyophilized thylakoid membranes of the thermophilic cyanobacterium
      Synechococcus sp. with n-heptane for 6 h resulted in marked changes in the
      pattern of photosystem I reaction center complexes resolved by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis. CP1-a, which consists of two
      large subunits and three small subunits, was a major chlorophyll-containing band
      resolved from the lyophilized thylakoid membranes, whereas the heptane-extracted
      membranes produced mainly CP1-e which totally lacks the small subunits. Electron
      transport from the primary donor P700 to the secondary acceptor P430 was not
      affected by the heptane-extraction of the membranes. The heptane-treatment
      removed 97% of beta-carotene present in the membranes, whereas all chlorophyll a,
      a major part of xanthophylls, more than a half of phylloquinone and one third of
      plastoquinone remained unextracted. The data suggest that beta-carotene has an
      important structural effect to stabilize the subunit organization of photosystem
      I reaction center complexes but is not essential for the early photochemical
      events of photosystem I. 

PMID- 24435461
TI  - Steady-state kinetics of the photosystem I reaction in chloroplasts of Dunaliella
      which contain variable concentrations of plastocyanin.
AB  - The endogenous plastocyanin (PC) concentrations of Dunaliella cultures were
      varied from 0.3 to 3.1 molecules per pigment 700 (P700) by decreasing the Cu(+)
      supply of the nutrient. With these cultures the amount of PC which is sufficient
      for maximum photosynthesis in intact cells was determined to be about 1 to 1.5
      PC/P700. Chloroplasts were also prepared from these cells and were employed in
      enzyme kinetic measurements of the PSI reaction from ascorbate reduced
      diaminodurene (DAD) to methylviologen/O2. The k m value for DAD in this reaction
      was 106 MUM. A decrease of the endogenous PC concentration caused no change of
      the k m value but affected the V max in the DAD-dependent reaction. A similar
      interference of the PC concentration on the maximum reaction rate could also be
      observed when the light intensity was varied. 

PMID- 24435462
TI  - On the nature of the oxygen uptake in the light by Chondrus crispus. Effects of
      inhibitors, temperature and light intensity.
AB  - The nature of the different processes of O2 uptake involved in the light in the
      red macroalga Chondrus crispus Stackhouse (Rhodophyta, Gigartinales) was
      investigated. At limiting CO2, INH (2.5 mM) did not alter the O2 uptake rate.
      Glycolate was not excreted and did not accumulate within the cells. KCN reduced
      the rate of O2 uptake in the light by 76% at limiting CO2 and by 43% at
      saturating CO2, but caused > 95% inhibition of O2 evolution. DCMU (5 MUM) totally
      blocked the photosynthetic electron transport chain, but allowed a residual O2
      uptake of 3.0+/-0.6 MUmol O2 .h(-1).g(-1) FW, irrespective of the CO2
      concentration. In saturating CO2, a high light intensity pretreatment
      significantly stimulated the rate of O2 uptake compared to net O2 evolution,
      suggesting the persistence, in the light, of mitochondrial respiration.
      Irrespective of the CO2 concentration, the optimum temperature for O2 evolution
      was 17 degrees C whereas dark O2 uptake increased linearly with temperature. In
      contrast, O2 uptake in the light showed an optimum at 17 degrees C in limiting
      CO2, and 21-25 degrees  C in saturating CO2; its Q10 was 2.4 at limiting CO2, a
      value close to that of RuBP oxygenase, and 3.1 at saturating CO2, a value close
      to that of dark respiration. It is concluded that: 1) mitochondrial respiration
      and Mehler reaction are both involved at all CO2 concentrations, 2) RuBP
      oxygenase activity cannot account for more than 45%, and Mehler reaction for less
      than 20%, of the total O2 uptake observed in the light at limiting CO2. 

PMID- 24435463
TI  - Diurnal patterns of canopy photosynthesis, evapotranspiration and water use
      efficiency in chickpea (Cicer arietinum L.) under field conditions.
AB  - Diurnal changes in net photosynthetic rate (PN), evapotranspiration rate (ET) and
      water use efficiency (WUE=PN/ET) of field grown chickpea (Cicer arietinum) L. cv.
      H-355 were studied from the vegetative phase through maturirty at Haryana
      Agricultural University Farm, Hissar, India. The maximum photosynthetic rate (PN
      max) increased from the initial vegetative phase to pod formation and declined at
      a rapid rate from pod filling to maturity. The response of PN to photosynthetic
      photon flux density (PPFD) (400-700 nm) was temperature-dependent during the day,
      i.e. on cool days the PN rates were lower for certain quanta of PPFD during the
      first half than during the second half of day, and vice versa on warm days. ET
      was affected both by crop cover and evaporative demand up to flowering, but
      thereafter it was independent of crop cover and followed the course of
      evaporative demand. ET was related to air temperature during the day while PN was
      related to PPFD. There was a lag of two to three hours between PNmax (around
      noon) and ETmax (around 2 p.m.). WUE increased from the vegetative stage through
      flowering but decreased thereafter to maturity. 

PMID- 24435464
TI  - The relationship between heat-stress and photobleaching in green and blue-green
      algae.
AB  - Two characteristic temperatures were identified from measurements of the
      temperature dependence of O2 evolution by Chlorella vulgaris and Anacystis
      nidulans: T1, the threshold temperature for inhibition of O2 evolution under
      saturating light conditions, and T2, the upper temperature limit for O2
      evolution. Measurement of delayed light emission from photosystem II (PSII)
      showed that it passed through a maximum at T1 and was virtually eliminated on
      heating the samples to T2. Related changes were observed in low-temperature (77K)
      fluoresence emission spectra. Heat-stress had little effect on the absorption
      properties of the cells at temperatures below T1 but incubation at higher
      temperatures, particularly under high-light conditions, resulted in extensive
      absorption losses. An analysis of these measurements suggests that this increased
      susceptibility to photobleaching is triggered by an inhibition of the flow of
      reducing equivalents from PSII that normally serves to protect the light
      harvesting apparatus of the cells from photo-oxidation. Adaptation to higher
      growth temperatures resulted in increases in the values of T1 and T2 for
      Anacystis nidulans but not for Chlorella vulgaris. 

PMID- 24435465
TI  - Characteristics of a photorespiratory mutant of barley (Hordeum vulgare L.)
      deficient in phosphogly collate phosphatase.
AB  - A barley mutant RPr84/90 has been isolated by selecting for plants which grow
      poorly in natural air, but normally in air enriched to 0.8% CO2. After 5 minutes
      of photosynthesis in air containing(14)CO2 this mutant incorporated 26% of
      the(14)C carbon into phosphoglycollate, a compound not normally labelled in wild
      type (cv. Maris Mink) leaves.The activity of phosphoglycollate phosphatase (EC
      3.1.1.18) was 1.2 nkat mg(-1) protein at 30 degrees C in RPr 84/90 compared to
      19.2 nkat mg(-1) protein in the wild-type leaves. Phosphoglycollate phosphatase
      activity was not detected after protein separation by electrophoresis of leaf
      extracts from the mutant on polyacrylamide gels; on linear 5% acrylamide gels
      three bands with enzyme activity were separated from extracts of wild type
      plants. Gradient gel electrophoresis followed by activity staining showed two
      bands in Maris Mink tracks of MW 86,000 and 96,000, but no bands in 84/90. This
      is the first report of isozymes of phosphoglycollate phosphatase in barley which
      were absent in the mutant extracts. Our results confirm an earlier report of
      isozymes of this phosphatase in Phaseolus vulgaris [18].The photosynthetic rate
      of RPr 84/90 in 1% O2, 350 MUl CO2 l(-1) was 9-12 mg CO2 dm(-2) h(-1) at 20
      degrees C, whereas the wild-type rate was 27-29 mg CO2 dm(-2) h(-1) at 20 degrees
      C. In 21% O2, 350 MUl CO2 l(-1) the rate was 2-3 mg CO2 dm(-2) h(-1) in the
      mutant and 20 mg CO2 dm(-2) h(-1) in the wild type.Genetic analysis has shown
      that the mutation segregates as a single recessive nuclear gene. 

PMID- 24435466
TI  - 17beta-estradiol downregulated the expression of TASK-1 channels in mouse
      neuroblastoma N2A cells.
AB  - TASK channels, an acid-sensitive subgroup of two pore domain K+ (K2P) channels
      family, were widely expressed in a variety of neural tissues, and exhibited
      potent functions such as the regulation of membrane potential. The steroid
      hormone estrogen was able to interact with K+ channels, including voltage-gated
      K+ (Kv) and large conductance Ca2+-activated (BK) K+ channels, in different types
      of cells like cardiac myocytes and neurons. However, it is unclear about the
      effects of estrogen on TASK channels. In the present study, the expressions of
      two members of acid-sensitive TASK channels, TASK-1 and TASK-2, were detected in
      mouse neuroblastoma N2A cells by RT-PCR. Extracellular acidification (pH 6.4)
      weakly but statistically significantly inhibited the outward background current
      by 22.9 % at a holding potential of 0 mV, which inactive voltage-gated K+
      currents, suggesting that there existed the functional TASK channels in the
      membrane of N2A cells. Although these currents were not altered by the acute
      application of 100 nM 17beta-estradiol, incubation with 10 nM 17beta-estradiol
      for 48 h reduced the mRNA level of TASK-1 channels by 40.4 % without any effect
      on TASK-2 channels. The proliferation rates of N2A cells were also increased by
      treatment with 10 nM 17beta-estradiol for 48 h. These data implied that N2A cells
      expressed functional TASK channels and chronic exposure to 17beta-estradiol
      downregulated the expression of TASK-1 channels and improved cell proliferation.
      The effect of 17beta-estradiol on TASK-1 channels might be an alternative
      mechanism for the neuroprotective action of 17beta-estradiol.

PMID- 24435467
TI  - Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose
      oil in patients with atopic dermatitis.
AB  - INTRODUCTION: Atopic dermatitis (AD) has been related to a deficiency of delta-6
      desaturase, an enzyme responsible for the conversion of linoleic acid to gamma
      linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA.
      Therefore, this study investigated whether EPO supplementation results in an
      increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA)
      correlating with clinical improvement of AD, assessed by the SCORing Atopic
      Dermatitis (SCORAD) index. METHODS: The open study included 21 patients with AD.
      EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12
      weeks after initiation of EPO supplementation, objective SCORAD was assessed and
      plasma concentrations of GLA and DGLA were determined by gas chromatography.
      RESULTS: A significant increase in plasma GLA and DGLA levels and a decrease in
      the objective SCORAD were observed 4 and 12 weeks after initiation of EPO
      treatment. In the per-protocol population (n = 14), a significant inverse
      correlation between the changes in plasma GLA levels and SCORAD was found (P =
      0.008). CONCLUSION: The clinical disease activity under EPO treatment correlates
      with the individual increase in plasma GLA levels. Thus, the results of this
      pilot study indicate that an increase in plasma GLA might be used as predictive
      parameter for responsiveness of AD to EPO therapy.

PMID- 24435469
TI  - A retrospective review of the progression of pediatric vocal fold nodules.
AB  - IMPORTANCE: To our knowledge, the rate of change in the size of pediatric vocal
      fold nodules (VFNs) has not been investigated. Improved understanding of the
      factors that affect change in VFN size may help to better guide treatment
      decisions and counselling of families. OBJECTIVE: To characterize the rate of
      change in the size of pediatric VFNs over time and to identify which factors
      affect increased rates of improvement. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective review of 67 children evaluated in a voice clinic between 2002 and
      2011 with a primary diagnosis of VFNs. EXPOSURE: No treatment or behavioral
      modification only (n = 19) vs targeted voice therapy with or without the
      treatment of associated conditions (gastroesophageal reflux and allergic
      rhinitis) (n = 45) vs surgical intervention (n = 3). MAIN OUTCOMES AND MEASURES:
      Change in VFN grade (graded according to a previously validated scale based on
      size) over time. RESULTS: Sixty-seven patients with a median (range) age of 6.0
      (3.8-20.6) years were analyzed. Median (range) follow-up was 25 (1-119) months.
      The rate of change in VFN grade over time was significantly associated with large
      baseline VFN size (P < .001) and targeted voice therapy with or without the
      management of associated conditions or surgery (P = .01); the association with
      postpubescent age was not significant (P = .09). The rate of change in VFN grade
      was not significantly different at 1 and 3 years postbaseline (P = .33).
      CONCLUSIONS AND RELEVANCE: Baseline VFN size, treatment, and patient age are
      important in predicting the rate of improvement in nodule size over time. Rate of
      change in VFN size is a gradual decrease that is steady over time. This
      information can be used to help guide treatment decisions and counsel families of
      children with VFNs regarding expectations for improvement. Additional study is
      needed to evaluate whether the same factors that influence nodule size similarly
      influence parental perception of voice and expert perceptual voice analysis.

PMID- 24435468
TI  - Effects of protein supplements on muscle damage, soreness and recovery of muscle
      function and physical performance: a systematic review.
AB  - BACKGROUND: Protein supplements are frequently consumed by athletes and
      recreationally-active individuals, although the decision to purchase and consume
      protein supplements is often based on marketing claims rather than evidence-based
      research. OBJECTIVE: To provide a systematic and comprehensive analysis of
      literature examining the hypothesis that protein supplements enhance recovery of
      muscle function and physical performance by attenuating muscle damage and
      soreness following a previous bout of exercise. DATA SOURCES: English language
      articles were searched with PubMed and Google Scholar using protein and
      supplements together with performance, exercise, competition and muscle, alone or
      in combination as keywords. STUDY SELECTION: Inclusion criteria required studies
      to recruit healthy adults less than 50 years of age and to evaluate the effects
      of protein supplements alone or in combination with carbohydrate on performance
      metrics including time-to-exhaustion, time-trial or isometric or isokinetic
      muscle strength and markers of muscle damage and soreness. Twenty-seven articles
      were identified of which 18 dealt exclusively with ingestion of protein
      supplements to reduce muscle damage and soreness and improve recovery of muscle
      function following exercise, whereas the remaining 9 articles assessed muscle
      damage as well as performance metrics during single or repeat bouts of exercise.
      STUDY APPRAISAL AND SYNTHESIS METHODS: Papers were evaluated based on
      experimental design and examined for confounders that explain discrepancies
      between studies such as dietary control, training state of participants, sample
      size, direct or surrogate measures of muscle damage, and sensitivity of the
      performance metric. RESULTS: High quality and consistent data demonstrated there
      is no apparent relationship between recovery of muscle function and ratings of
      muscle soreness and surrogate markers of muscle damage when protein supplements
      are consumed prior to, during or after a bout of endurance or resistance
      exercise. There also appears to be insufficient experimental data demonstrating
      ingestion of a protein supplement following a bout of exercise attenuates muscle
      soreness and/or lowers markers of muscle damage. However, beneficial effects such
      as reduced muscle soreness and markers of muscle damage become more evident when
      supplemental protein is consumed after daily training sessions. Furthermore, the
      data suggest potential ergogenic effects associated with protein supplementation
      are greatest if participants are in negative nitrogen and/or energy balance.
      LIMITATIONS: Small sample numbers and lack of dietary control limited the
      effectiveness of several investigations. In addition, studies did not measure the
      effects of protein supplementation on direct indices of muscle damage such as
      myofibrillar disruption and various measures of protein signaling indicative of a
      change in rates of protein synthesis and degradation. As a result, the
      interpretation of the data was often limited. CONCLUSIONS: Overwhelmingly,
      studies have consistently demonstrated the acute benefits of protein
      supplementation on post-exercise muscle anabolism, which, in theory, may
      facilitate the recovery of muscle function and performance. However, to date,
      when protein supplements are provided, acute changes in post-exercise protein
      synthesis and anabolic intracellular signaling have not resulted in measureable
      reductions in muscle damage and enhanced recovery of muscle function. Limitations
      in study designs together with the large variability in surrogate markers of
      muscle damage reduced the strength of the evidence-base.

PMID- 24435470
TI  - Palladium catalyzed acetoxylation of benzylic C-H bonds using a bidentate
      picolinamide directing group.
AB  - A general palladium catalyzed acetoxylation of benzylic C-H bonds has been
      developed. Picolinamides serve as an excellent directing group for the C-H
      activation of benzylic methyls. A wide range of 2-amino benzyl alcohol analogues
      were synthesized in good yields. The products demonstrated broad synthetic
      utilities toward various benzo-fused heterocycles. Mechanistic studies revealed
      the key rate-limiting C-H insertion step, which could be affected by the
      substitution pattern of the parent arene. 

PMID- 24435472
TI  - Outcomes after biological mesh reconstruction of the pelvic floor following extra
      levator abdominoperineal excision of rectum (APER).
AB  - BACKGROUND: Extra-levator abdominoperineal excision of the rectum (ELAPER) for
      low rectal cancer is used to avoid the adverse oncological outcomes of
      inadvertent perforation and a positive circumferential resection margin
      associated with the conventional APER technique. This wider excision creates a
      large defect requiring pelvic floor reconstruction, and there is still
      controversy regarding the best method of closure. The aim of this study is to
      present outcomes of biological mesh pelvic floor reconstruction following ELAPER.
      METHODS: Prospective data on consecutive patients having ELAPER for low rectal
      cancer at a single UK institution between October 2008 and March 2013 were
      collected. The perineum was reconstructed using a biological mesh and the short
      term outcomes were evaluated, focusing particularly on perineal wound
      complications and perineal hernias. RESULTS: Thirty-four patients were included
      [median age 62 years, range 40-72 years, 27 males (79 %)]. The median operative
      time was 248 min (range 120-340 min). The median length of hospital stay was 9
      days (range 4-20 days). There were three perineal complications (9 %) requiring
      surgical intervention, but no meshes were removed. There were no perineal
      hernias. The median length of follow-up was 21 months (range 1-54 months). The
      overall mortality was 9 % from distant metastases. CONCLUSIONS: Our series adds
      to the increasing evidence that good outcomes can be achieved for pelvic floor
      reconstruction with biological mesh following ELAPER without the additional use
      of myocutaneous flaps. The low serious complication rate, good outcomes in
      perineal wound healing and the absence of perineal hernias demonstrates that this
      is a safe and feasible procedure.

PMID- 24435473
TI  - A modified total colonic exclusion for elderly patients with severe slow transit
      constipation.
AB  - BACKGROUND: The aim of this study was to evaluate outcomes of total colonic
      exclusion with antiperistaltic ileorectal anastomosis (TCE-AIA) for elderly
      patients with slow transit constipation (STC). METHODS: Elderly patients (defined
      as age >65) who underwent TCE-AIA for severe idiopathic STC between 2009 and 2012
      at our institution were identified. Postoperative outcomes and routine follow-up
      were assessed using the Wexner constipation score (WCS), gastrointestinal quality
      of life index (GIQLI) and four-point postoperative satisfaction scales. RESULTS:
      A total of 13 elderly patients were met the inclusion criteria. Five patients
      (38.5%) were male, and eight patients (61.5%) were female. The mean age of this
      population was 74 years (range 63-82 years). The mean operative time was 55 min
      (range 28-32), and blood loss was minimal. The mean postoperative hospital stay
      was 6.7 days (range 5-12 days). The mean time until the first postoperative bowel
      movement was 4 days (range 2-8 days). There was no procedure-related mortality
      and no major in-hospital complications. The median duration of follow-up was 12.4
      months (range 6-29 months). None of the 13 patients had fecal incontinence or
      recurrence of constipation at the follow-up end point. However, eight patients
      underwent colonoscopy during follow-up, and four patients presented with
      diversion colitis. The patients' preoperative WCS was 22.8 +/- 3.3, and it had
      significantly improved to 5.4 +/- 2.1 on 6 months after operation (p < 0.05). The
      preoperative GIQLI of 93.6 +/- 20.5 had significantly increased to 120.8 +/- 13.0
      on 6 months after surgery (p < 0.05). Patient satisfaction at 6 months was very
      high in 11 patients and high in two patients. CONCLUSIONS: TCE-AIA is a
      relatively simple procedure. It might be an effective surgical intervention for
      the selected elderly patients with STC.

PMID- 24435475
TI  - A novel nickel metal-organic framework with fluorite-like structure: gas
      adsorption properties and catalytic activity in Knoevenagel condensation.
AB  - A new non-interpenetrating 3D metal-organic framework {[Ni4(MU6-MTB)2(MU2
      H2O)4(H2O)4].10DMF.11H2O}n (DMF = N,N'-dimethylformamide) built from nickel(ii)
      ions as connectors and methanetetrabenzoate ligands (MTB(4-)) as linkers has been
      synthesized and characterized. The single crystal X-ray diffraction showed that
      complex exhibits CaF2-like fluorite structure topology and four types of 3D
      channels with sizes about 12.6 * 9.4 A(2), 9.4 * 8.0 A(2), 12.6 * 11.7 A(2) and
      14.9 * 14.9 A(2), which are filled with guest molecules. Conditions of the
      activation of the compound have been studied and optimized by powder X-ray
      diffraction during in situ heating, thermogravimetric analysis and infrared
      spectroscopy. Nitrogen and carbon dioxide adsorption showed that the activated
      sample exhibits a BET specific surface area of 700 m(2) g(-1) and a carbon
      dioxide uptake of 12.36 wt% at 0  degrees C, which are the highest values
      reported for the compounds of the MTB(4-) series. The complex was tested in
      Knoevenagel condensation of aldehydes and active methylene compounds.
      Straightforward dependence of the substrate conversion on the size of used
      aldehyde was established. A possible mechanism of Knoevenagel condensation over a
      MTB(4-) containing a metal-organic framework was proposed. 

PMID- 24435474
TI  - Restoration of intestinal continuity after colectomy for non-occlusive ischemic
      colitis.
AB  - BACKGROUND: Non-occlusive ischemic colitis (IC) is a rare and life-threatening
      abdominal disease associated with high rates of postoperative mortality. When
      surgery is performed, in patients with IC, either a Hartmann's procedure (HP) or
      a total colectomy and ileostomy is required. The possibility of restoration of
      intestinal continuity in surviving patients is an important issue. The aim of the
      present study was to report the outcome of surgically managed IC patients and to
      identify predictive factors for restoration of intestinal continuity and to
      assess the results of this procedure. METHODS: Between January 1997 and May 2011,
      96 IC patients underwent total colectomy and 68 underwent left colectomy. IC was
      spontaneous in 62 patients and occurred after prior surgery in 102. Eighty
      patients died during the postoperative period and nine died during the follow-up
      from an unrelated disease. Fifteen patients were lost to follow-up. The remaining
      60 surviving patients were our study population. RESULTS: There were 44 men and
      16 women with a mean age of 67 years +/- 12 SD. Restoration of bowel continuity
      was performed in 24 patients (40%). There were no predictive factors for
      restoration of intestinal continuity in terms of sex, age, IC etiology, and the
      extent of colon resection at primary surgery. The median interval between first
      surgery and restoration of bowel continuity was 7.9 months (range 0.2-35 months).
      There were no postoperative deaths and the overall morbidity rate was 45%
      (11/24). No patients developed anastomotic leak or underwent unplanned
      reoperation. CONCLUSIONS: Reversal of HP after IC is feasible in 40% of surviving
      patients with acceptable mortality and morbidity rates. This restoration of
      intestinal continuity should therefore be discussed for every surviving IC
      patient.

PMID- 24435476
TI  - Polybrominated diphenyl ethers and perfluoroalkyl substances in serum of pregnant
      women: levels, correlations, and potential health implications.
AB  - Polybrominated diphenyl ethers (PBDEs), a group of flame retardants, and
      perfluoroalkyl substances (PFASs) were analysed in serum samples of pregnant
      women from Denmark to provide information about their exposure and to study
      indications of common exposure pathways. The main BDE congener was the fully
      brominated BDE-209 with a median value of 7.5 ng/g lipid (46 pg/mL; 9.8 pmol/g
      lipid). Other BDE congeners decreased in the order BDE-47 > BDE-99 > BDE-153. The
      summed concentration of tri- to hepta-BDEs was 7.7 ng/g lipid, i.e. in the higher
      end of previously reported concentrations from Europe, including plasma samples
      of pregnant Danish women. Total lipid contents were relatively low, on average
      5.9 g/L (9.0 mmol/L). The main PFAS compound was perfluorooctane sulfonate with a
      median concentration of 8.4 ng/mL. Other PFASs decreased in the order
      perfluorooctanoic acid > perfluorononanoic acid > perfluorodecanoic acid >
      perfluorohexane sulfonate and resulted in a SigmaPFAS of 12 ng/mL. Within each
      group, compounds were highly intercorrelated with the exception of BDE-209, which
      was not correlated with any of the other compounds. No correlations were found
      either between PFASs and PBDEs suggesting different sources of exposure and/or
      pharmacokinetic and metabolisation processes. PBDE and PFAS concentrations were
      in the range associated with adverse effects in some epidemiological studies. 

PMID- 24435477
TI  - Genotoxicity in Astyanax bimaculatus (Twospot Astyanax) exposed to the waters of
      Engano River (Brazil) as determined by micronucleus tests in erythrocytes.
AB  - Changes in aquatic environments are potentially large, and effects on biota are
      highly variable. In Santa Catarina State, Brazil, the main sources of pollution
      in headwaters are wastewater, pesticides, and animal waste, which contain
      chemical and organic additives, and there is little knowledge about their effects
      on aquatic organisms. This study was aimed at investigating the possible
      genotoxic effects of the waters of the Engano River through the micronucleus (MN)
      test in Astyanax bimaculatus erythrocytes. Samplings were performed at two sites
      on the river, and there were six temporal repetitions with collection of blood
      from six individuals per site/repetition. For the negative-control treatment, we
      used fish from organic culture; cyclophosphamide was inoculated to constitute the
      positive-control treatment. MN was obtained in 3,000 erythrocytes/individual.
      Kruskal-Wallis analysis of variance, Scott-Knott test, and Spearman correlation
      were employed for data analysis. We found 124 MN in fish from the river, with 70
      and 54 MN, respectively, for each site and 16 and 59 MN in negative and positive
      controls, respectively. The results showed a statistical difference for the
      formation of MN between river fish and fish in the positive-control treatment.
      Considering the average MN, we found the formation of three distinct groups: (1)
      fish from site no. 1 and those in the negative-control group, (2) fish from site
      no. 2, and (3) fish in the positive-control group. The greater values of
      chromosomal damage were found during periods of lower rainfall. The test used
      indicated the presence in the water of substances likely to cause clastogenic and
      aneugenic effects. 

PMID- 24435478
TI  - Proteomic comparison between abdominal and thoracic aortic aneurysms.
AB  - The pathogenesis of abdominal aortic aneurysms (AAAs) and that of thoracic aortic
      aneurysms (TAAs) is distinct. In this study, to reveal the differences in their
      biochemical properties, we performed quantitative proteomic analysis of AAAs and
      TAAs compared with adjacent normal aorta (NA) tissues. The proteomic analysis
      revealed 176 non-redundant differentially expressed proteins in the AAAs and 189
      proteins in the TAAs which were common in at least 5 samples within 7 samples of
      each. Among the identified proteins, 55 and 68 proteins were unique to the AAAs
      and TAAs, respectively, whereas 121 proteins were identified in both the AAAs and
      TAAs. Panther overrepresentation analysis of the unique proteins in the AAAs and
      TAAs revealed a significant downregulation of the blood coagulation pathway in
      the AAAs and that of the integrin signaling pathway in the TAAs. On the other
      hand, Genesis analysis revealed distinct expression patterns of 58 proteins among
      the 121 proteins. Panther overrepresentation analysis of these 58 proteins
      revealed that the expression of these proteins in the blood coagulation and the
      plasminogen activating cascade was decreased in the AAAs, whereas it was
      increased in the TAAs compared with the NA tissues. On the other hand, the
      protein expression in the integrin signaling pathway was increased in the AAAs,
      whereas it was decreased in the TAAs compared with the NA tissues. Thus, the data
      presented in this study indicate that the proteins that show differential
      expression patterns in AAAs and TAAs may be involved in the distinct pathogenesis
      of AAAs and TAAs.

PMID- 24435479
TI  - Stereoselective iron-catalyzed alkyne hydrogenation in ionic liquids.
AB  - Iron(0) nanoparticles in ionic liquids (ILs) have been shown to catalyse the semi
      hydrogenation of alkynes. In the presence of a nitrile-functionalised IL or
      acetonitrile, stereoselective formation of (Z)-alkenes was observed. The biphasic
      solvent system allowed facile separation and re-use of the catalyst. 

PMID- 24435480
TI  - Radiation effects on the one locus-gametophytic system of self-incompatibility in
      higher plants : A review.
AB  - A brief review is presented of the temporary and permanent effects which are
      usually observed after irradiation treatment of self-incompatible plants with a
      one locus-system of gametophytic incompatibility and attempts are made to
      demonstrate that the study and exploitation of such effects can lead to important
      advances in the fields of mutation breeding, radiobiology per se and
      biochemistry.The fact that irradiation treatment has only negative effects on the
      self-incompatibility system (inactivation of the incompatibility reaction and/or
      genetic losses at the S locus) is discussed in relation to the positive changes
      (formation of new specificities) which are observed during inbreeding. In this
      connection, the suggestion is made that the self-incompatible plant may perhaps
      be equipped with a switch system or a mutagenic mechanism which enables it to
      display a new specificity when this new specificity is needed for increasing the
      level of genetic polymorphism in the population to which the plant belongs. 

PMID- 24435481
TI  - [Investigations on variability of pollen tube growth in diploid and tetraploid
      plants of sugar beet : I. Conditions for germination of Beta pollen in vitro].
AB  - a) Attempts to germinate freshly harvested pollen of Beta vulgaris L. on
      semisolid media were carried out in 1966/67. The basic nutrient medium consisted
      of 5% gelatin, 30% sucrose and 0.03% boric acid (pH 6.4). Very poor germination
      occurred in aqueous solutions. During the flowering time from August to October
      the pollen was taken from field grown plants and during the rest of the year from
      greenhouse plants. b) One of the requirements for satisfactory in vitro
      germination rates is the optimal degree of ripeness of the pollen grains which is
      attained immediately after the dehiscence of the anthers. c) From January to
      March in vitro germination was very poor. Highest germination rates occurred
      during August and September. d) The germination of Beta pollen is strictly
      dependent upon the presence of boron in the medium. Optimal concentration of
      boric acid for pollen germination is 10(-1)% and for pollen tube growth 10(-2)% ;
      pollen tubes in this case reached a maximum length of 750 MUm, in rare cases even
      of up to 1200 MUm. Borax and butyl boric acid are less active in promoting
      germination. Phenyl boric acid has a very slight promoting effect and becomes
      toxic with concentrations higher than 10(-3)%. e) Highest germination rates (85%)
      were obtained on the basic medium at pH 5.4 to 5.7 after addition of n/10 HCl.
      Ca(++)-ions had no positive effect on germination. f) Germination of Beta pollen
      as compared to other pollen is relatively slow. g) A coating of callose was
      always observed on the inside of the walls of in vitro grown pollen tubes, less
      frequently callose plugs were found. Occasionally branching of the tubes
      occurred. 

PMID- 24435482
TI  - Some genetic aspects of the symbiotic relationship between white clover
      (Trifolium repens) and Rhizobium Trifolii.
AB  - The results of experiments with white clover (Trifolium repens) in which time of
      nodulation and seedling plant weight or vigour were measured are reported.
      Experiments 1 and 2 were conducted in artificial growth medium in test tubes with
      controlled inoculation and experiment 3 in soil without controlled inoculation.
      Experiment 1 which was preliminary in nature showed the extent of the variation
      for time of nodulation after inoculation with Rhizobium trifolii. It was evident
      also that plant vigour and the number of days to nodulation were negatively
      correlated. Experiment 2 forms the major part of the results and is concerned
      with the analyses and interpretation of the diallel cross progeny of twelve
      plants selected from experiment 1. The results indicated a rather complex genetic
      picture for the two characters measured, namely days to nodulation and seedling
      plant weight at 80 days. Reciprocal (both general and specific) as well as
      additive (g.c.a.) and non-additive (s.c.a.) effects were present. Experiment 3,
      in which seed from 22 families of the diallel cross was sown in soil without
      controlled inoculation, indicated that the results obtained under the laboratory
      conditions of experiment 2 and those obtained in soil conditions were not
      correlated. The implications of these results in relation to selection of
      improved varieties of the host species are discussed. 

PMID- 24435483
TI  - [Investigations of the needle foliage relations of spruce].
AB  - 1. Previous studies of the needle foliage of spruces have mainly dealt with the
      question of the existence of a possible relation between needle volume and growth
      increment. The present paper addresses itself to the following points: a) What
      characters are important for the description of the needle foliage conditions of
      spruce ? b) What are the mean values of these characters and what are their
      standard deviations ? c) What influence have hereditary disposition and
      environmental factors respectively on the development of the characters ? d) What
      conclusions can be drawn for breeding purposes? The investigations are based on
      extensive material, composed of different provenience tests and evaluations of
      single trees. 2. For the character needle age class a relationship to the
      altitude of the locality of origin could not be shown. Environmental factors such
      as drought, nutritional difficulties, light conditions, effects of competition
      and exposure have such an influence that the needle age by itself cannot be used
      to characterize the condition of the needle foliage. 3. Differences in needle
      length are individually determined and therefore do not overlap the differences
      between the localities of origin. The absolute values are greatly influenced by
      environmental conditions. As a rule, shortened needles will develop in the growth
      period following a drought year. Although the genetical component will manifest
      itself very strongly, needle length cannot be used as a characteristic or serve
      as a basis to initiate selection. The average needle length of the test material
      was 15.18+/-2.46 mm. 4. The average surface area of a needle was found to be
      36.61+/-8.34 mm(2). On the average 1211+/-443 stomata are arranged in 9.7 rows on
      this surface. Within a tree close correlations exist between needle length and
      needle surface, but if one compares several trees these correlations no longer
      hold. 5. A correlation of up to 90% was found between the "Thousand-needle-dry
      weight" (TNG=3.30+/-0.95 g) and surface of the needles. This character may be
      used for the determination of the assimilation surface. Spruce trees from the
      same locality of origin may form greatly variable amounts of needles depending on
      the test sites. The differences increase with increasing ecological differences
      of the test locations. A very close correlation exists also between dry needle
      weight and altitude of the locality of origin on the one hand and dependence on
      the test site on the other hand, so that the adaptability of trees of different
      provenience to the new location may be estimated. 6. Comparisons of the needle
      foliage relations of several trees from several localities of origin on different
      soil locations may result in considerable shifts in the order of precedence and
      of other relationships. Conclusions as to the suitability for a certain site as
      well as an estimate of the genetical fixation of the potential efficiency up to
      an estimated maximum may be drawn. It may also be possible to determine an
      optimal range. These determinations are correlated with the question of the
      expediency of intensification measures, i.e. support by application of
      fertilizers. 7. The marked influence of the environment on the main characters
      under investigation prevents the selection of plus variants, whose superiority of
      performance would be based on characteristics of the needle foliage. Individuals
      which are to be tested, must therefore be propagated autovegetatively, and these
      clones must then be cultivated in different soil locations and be compared with
      regard to their needle characters. Experiments of this kind are now in progress. 

PMID- 24435484
TI  - [Susceptibility of leaves and fruits of tomato varieties and of their hybrids to
      attack by Phytophthora infestans].
AB  - 1. The investigations were started to establish a correlation between the
      incidence of Phytophthora infestans (Mont.) de Bary on leaves and on fruits of
      tomatoes, the mechanism of the inheritance of the resistance and the number of
      responsible genes. 2. A close correlation was found between the spontaneous
      incidence on leaves and fruits and the results of artificial inoculation by the
      leaf-disc-test. The resistant types especially showed a remarkably low percentage
      of attack in all three tests. Resistant plants were successfully selected by
      means of the leaf-disc-test; the leaves as well as the fruits of the progeny were
      largely free from the disease. 3. The field-resistance of the variety 'Atom' was
      demonstrated to be due to a high degree of relative resistance of the leaves
      against the races T0 and T1. 4. The results obtained from F1-hybrids of 'Atom'
      with various more or less susceptible varieties indicate the participation of
      incompletely dominant genes. Since in the F2 a certain number of plants with a
      high degree of field-resistance could be selected, it is suggested that the field
      resistance against Phytophthora infestans is based on a few genes only. From our
      results we conclude that principally two genes in the variety 'Atom' determine
      the field-resistance against the fungus. A participation of other modifier-genes
      can be supposed. We propose the gene-symbols Phf and Phf-2 for the Phytophthora
      field-resistance. 

PMID- 24435486
TI  - The state of activation of ribulose-1,5-bisphosphate carboxylase in wheat leaves.
AB  - In light and in darkness, exposure of leaf segments to CO2-free atmospheres
      caused a marked reduction in extractable RuBP carboxylase activity. By contrast,
      darkness caused a relatively small decrease in carboxylase activity in extracts
      from leaf segments kept in air containing CO2. Recovery of carboxylase activity
      in leaves during illumination in air after exposure to CO2-free conditions
      paralleled recovery of capacity for photosynthesis; in darkness recovery of
      carboxylase activity in leaves was slower than in the light. Extracts from leaves
      exposed to CO2-free conditions recovered activity when provided with CO2 and
      Mg(2+); there were clearly, however, substances in the extracts that modified the
      activity achieved and caused anomalous decreases and increases with time after
      extraction. Studies of the effect of orthophosphate on the activity of purified
      wheat carboxylase in vitro were consistent with the view that many of the effects
      observed on the activity of crude leaf extracts were due to orthophosphate
      content. 

PMID- 24435485
TI  - The impact of hospitalist discontinuity on hospital cost, readmissions, and
      patient satisfaction.
AB  - BACKGROUND: Achieving patient-physician continuity is difficult in the inpatient
      setting, where care must be provided continuously. Little is known about the
      impact of hospital physician discontinuity on outcomes. OBJECTIVE: To determine
      the association between hospital physician continuity and percentage change in
      median cost of hospitalization, 30-day readmission, and patient satisfaction with
      physician communication. DESIGN: Retrospective observational study using various
      multivariable models to adjust for patient characteristics. PARTICIPANTS:
      Patients admitted to a non-teaching hospitalist service in a large, academic,
      urban hospital between 6 July 2008 and 31 December 2011. MAIN MEASURES: We used
      two measures of continuity: the Number of Physicians Index (NPI), and the Usual
      Provider of Continuity (UPC) index. The NPI is the total number of unique
      physicians caring for a patient, while the UPC is calculated as the largest
      number of patient encounters with a single physician, divided by the total number
      of encounters. Outcome measures were percentage change in median cost of
      hospitalization, 30-day readmissions, and top box responses to satisfaction with
      physician communication. KEY RESULTS: Our analyses included data from 18,375
      hospitalizations. Lower continuity was associated with modest increases in costs
      (range 0.9-12.6 % of median), with three of the four models used achieving
      statistical significance. Lower continuity was associated with lower odds of
      readmission (OR = 0.95-0.98 across models), although only one of the models
      achieved statistical significance. Satisfaction with physician communication was
      lower, with less continuity across all models, but results were not statistically
      significant. CONCLUSIONS: Hospital physician discontinuity appears to be
      associated with modestly increased hospital costs. Hospital physicians may revise
      plans as they take over patient care responsibility from their colleagues.

PMID- 24435487
TI  - Observation and characterisation of a transient in the yield of chlorophyll
      fluorescence in intact spinach chloroplasts.
AB  - A transient in chlorophyll fluorescence, which is associated with a transient in
      9-aminoacridine fluorescence and a perturbation in the rate of oxygen evolution,
      has been observed in intact spinach chloroplasts. The results indicate that
      changes in the redox state of Q are, at least partially, responsible for the
      transient in chlorophyll fluorescence. The size of the transient is highly
      dependent upon the concentration of inorganic phosphate and upon the pH of the
      medium. The properties of the transient are consistent with the suggestion that
      it reflects changes in the levels of stromal intermediates during induction. 

PMID- 24435488
TI  - Sudden changes in the rate of photosynthetic oxygen evolution and chlorophyll
      fluorescence in intact isolated chloroplasts: the role of orthophosphate.
AB  - Simultaneous "ripples" (sudden changes in rate) in CO2 dependent O2 evolution and
      associated chlorophyll a fluorescence were followed in isolated, largely intact,
      spinach chloroplasts. These ripples could only be observed under conditions in
      which the supply of inorganic phosphate was limiting. This limitation was
      achieved either by 1) omission of phosphate in the assay medium, 2) use of
      inhibitors of the phosphate translocator, or 3) the addition of triose phosphate,
      a competitive inhibitor of Pi for the same translocator.The possible relation of
      these ripples to the dampening oscillations that can be observed in leaves, leaf
      pieces, isolated cells and protoplasts, is discussed. 

PMID- 24435489
TI  - Chlorophyll fluorescence transients from the diatom Phaeodactylum tricornutum:
      relative rates of cyclic phosphorylation and chlororespiration.
AB  - In Phaeodactylum tricornutum cells kept 30 min in the dark, induction of
      fluorescence showed the well-known levels OIDPSMT. The decrease of MT was the
      most important when the intensity of excitation light was high. It was mainly due
      to the photochemical quenching. After addition of DCMU (2 to 20 MUM), a quenching
      qE was still observed: this quenching, cancelled by NH4Cl (2 to 20 mM) is
      attributed to DeltapH. This qE was also inhibited by antimycin, an inhibitor of
      cyclic phosphorylation and may be of chlororespiration above plastoquinones.
      Anaerobiosis also decreased it. We can infer that chlororespiration also plays a
      part in the formation of the DeltapH in the presence of DCMU. After 30 mn of
      preillumination in red light, the levels P and M were lower and the quenching in
      presence of DCMU was no more observed: thus, neither the chlororespiration nor
      the cyclic phosphorylation were active, unless the activity of ATPase was much
      more important. So, in diatoms, one at least of the above cited phenomena can be
      modulated by light. 

PMID- 24435490
TI  - Evidence for a light-harvesting chlorophyll a-protein complex in a chlorophyll b
      less barley mutant.
AB  - Chloroplasts of a chlorophyll (Chl) b-less barley mutant were solubilized with
      digitonin and fractionated by polyacrylamide gel electrophoresis with sodium
      deoxycholate in the running buffer. By this procedure, in contrast to using
      sodium dodecylsulfate (SDS) for solubilization, a Chl a-protein analogous to the
      major light-harvesting Chl a-b protein complex from wildtype chloroplasts was
      recovered. This mutant Chl a-protein comprises about fifty percent of the total
      Chl a, and is very similar in carotenoid, amino acid, protein and polypeptide
      composition to the major wildtype antenna Chl a-b protein. The only major
      differences we have found is its instability in the presence of SDS and
      sensitivity to protease action. Even with deoxycholate, the mutant Chl a complex
      often dissociates during electrophoresis into two green bands. The lack of Chl b
      appears to affect the normal organization of Chl a and protein in such a way as
      to render the complex more unstable. 

PMID- 24435491
TI  - Inhibition of phosphoenolpyruvate carboxylase from maize by 2-phosphoglycollate.
AB  - The phosphoenolpyruvate carboxylase from maize leaf was strongly inhibited by 2
      phosphoglycollate. The pH of the reaction did not influence the extent of
      inhibition by 2-phosphoglycollate. The kinetic analysis of the inhibition data by
      Lineweaver-Burk method showed that 2-phosphoglycollate inhibition was competitive
      with respect to phosphoenolpyruvate. The secondary plot of the data showed
      nonlinearity indicating that there may be two 2-phosphoglycollate binding sites
      with Ki values of 0.4 mM and 0.16 mM. The biphasic nature of the inhibition was
      also evident when the data were plotted using the method of Dixon. 2
      phosphoglycollate inhibition was uncompetitive with respect to Mg(2+) suggestting
      that it binds only to enzyme-Mg(2+) complex. 

PMID- 24435492
TI  - Regulation of the photosynthetic electron transport during dark-light transitions
      by activation of the ferredoxin-NADP(+)-oxidoreductase in higher plants.
AB  - Absorbance changes associated with the oxidation and reduction of cytochrome f
      belong to the classical observations about the interaction of the two
      photosystems. A complex induction pattern of cytochrome f oxidation results, if
      both photosystems are excited simultaneously. This indicates a light-modulated
      regulation of the photosynthetic electron transport, which we examined for intact
      biological systems of decreasing complexity. The ferredoxin-NADP(+)
      oxidoreductase (FNR) is suggested to be activated by light and inactivated in the
      dark. This is pointed out by the kinetics of variable fluorescence and by the
      influence of different artificial electron acceptors on the cytochrome f
      kinetics. The photoreduction of NADP(+) by carefully prepared thylakoids
      demonstrates the activation process directly. 

PMID- 24435493
TI  - A solid-state, portable instrument for measurement of chlorophyll luminescence
      induction in plants.
AB  - A newly developed compact instrument is described for the measurement of
      chlorophyll luminescence induction in plants. The instrument operates with a
      pulsed light emitting diode (LED) as light source and a photodiode as
      luminescence detector. A special emitter-detector geometry provides for high
      irradiance of the sample and efficient collection of luminescence by the
      detector. With insertion of appropriate filters the same probe is also suited for
      measuring prompt chlorophyll fluorescence. The instrument shows considerable
      flexibility with respect to pulse frequency, relative lengths of light/dark
      intervals and luminescence sampling periods. Due to a selective amplifier system
      only that part of luminescence is processed which is induced by the individual
      excitation pulses. By this approach, the problem of "slow phase accumulation",
      encountered with conventional phosphoroscopes, is eliminated. Some examples are
      given for system operation, demonstrating satisfactory performance in
      measurements with intact leaves and isolated chloroplasts. 

PMID- 24435494
TI  - Differences between Fragaria clones by fourth derivative room temperature
      spectroscopy of intact leaves.
AB  - Clones of Fragaria were characterized by the attenuance (absorption) spectra of
      their photosynthetic apparatus. This method uses fourth derivative analysis of
      spectra of intact lamina of detached leaves at room temperature (20-25 C). Twenty
      one different species and hybrids of Fragaria were examined. F. chiloensis
      accessions frequently have characteristic fourth derivative spectra distinct from
      that of other Fragaria species. These spectra are characterized by a strong band
      that appears to be photosystem I component Ca 693; and is correlated with a
      higher chlorophyll b content per unit area of leaf, and a lower chlorophyll a/b
      ratio. 

PMID- 24435495
TI  - Data sharing matters.

PMID- 24435497
TI  - Tumor-free distance from outermost layer of cervix is of prognostic value in
      surgically treated cervical cancer patients: a multicenter study.
AB  - OBJECTIVE: This study aimed at determining if tumor-free distance (TFD) from
      outermost layer of cervix predicts surgicopathologic factors and outcome in
      surgically treated cervical cancer patients. MATERIALS AND METHODS: One hundred
      sixteen surgically treated cervical squamous cell carcinomas between 1991 and
      2010 with FIGO stage IB/2A were identified and re-evaluated histologically
      regarding the TFD. TFD was defined as the distance between outermost layer of
      cervix and deepest cervical stromal invasion. Depth of invasion (DOI) and TFD
      were expressed as continuous variables and compared with traditional
      surgicopathologic variables and survival to determine their prognostic
      significance. RESULTS: The mean DOI was 10.3 mm and the mean TFD was 4.2 mm. The
      most common stage was IB1 (60 patients, 51.7 %). The mean number of removed
      pelvic lymph nodes was 32.2 (median 30; range 8-78). Positive pelvic lymph nodes
      were found in 27 (23 %) of the patients. Sixty-eight patients had lymphovascular
      space involvement (LVSI). Sixty-eight patients (59 %) received postoperative
      radiotherapy where the following items were present: tumor diameter >4 cm,
      positive lymph nodes, LVSI and positive surgical margins. With the median follow
      up of 53 months (3-219 months); 14 patients had local and 13 patients had distant
      metastases (5 of the patients had both at the time of recurrence). With logistic
      regression analysis, TFD was a predictor of pelvic lymph involvement (p = 0.028)
      and LVSI (p = 0.008) while DOI was a predictor of LVSI (p = 0.044). In Cox
      regression analysis, increased TFD was associated with improved disease-free
      survival (DFS) (p = 0.007). DFS curves (for TFD cut off value 2.5 mm) according
      to Kaplan-Meier were found to be statistically significant (log rank test =
      0.002). CONCLUSION: The results indicate that TFD is predictive of pelvic lymph
      node involvement, LVSI and patient outcome in surgically treated cervical cancer
      patients. However, prospective measurement of TFD is still necessary to determine
      its value in clinical practice.

PMID- 24435496
TI  - Identification and expression analysis of ethylene biosynthesis and signaling
      genes provides insights into the early and late coffee cultivars ripening
      pathway.
AB  - The plant hormone ethylene is involved in the regulation of a multitude of plant
      processes, ranging from seed germination to organ senescence. Ethylene induces
      fruit ripening in climacteric fruits, such as coffee, being directly involved in
      fruit ripening time and synchronization. Coffee early cultivars usually show a
      more uniform ripening process although little is known about the genetic factors
      that promote the earliness of ripening. Thus, this work aimed to characterize the
      putative members of the coffee (Coffea arabica) ethylene biosynthesis and
      signaling pathways, as well as to analyze the expression patterns of these
      members during fruit ripening of early (Catucai 785-15) and late (Acaua) coffee
      cultivars. Reverse Transcription-qPCR analysis of the four biosynthesis genes
      (CaACS1-like; CaACO1-like; CaACO4-like e CaACO5-like) analyzed in this study
      showed that CaACO1-like and CaACO4-like displayed an expression pattern typically
      observed in climacteric fruits, being up-regulated during ripening. CaACS1-like
      gene expression was also up-regulated during fruit ripening of both cultivars,
      although in a much lesser extent when compared to the changes in CaACO1-like and
      CaACO4-like gene expression. CaACO5-like was only induced in raisin fruit and may
      be related to senescence processes. On the other hand, members of the ethylene
      signaling pathway (CaETR1-like, CaETR4-like, CaCTR2-like, CaEIN2-like, CaEIN3
      like, CaERF1) showed slightly higher expression levels during the initial stages
      of development (green and yellow-green fruits), except for the ethylene receptors
      CaETR1-like and CaETR4-like, which were constitutively expressed and induced in
      cherry fruits, respectively. The higher ethylene production levels in Catucai 785
      15 fruits, indicated by the expression analysis of CaACO1-like and CaACO4-like,
      suggest that it promotes an enhanced CaETR4-like degradation, leading to an
      increase in ethylene sensitivity and consequently to an earliness in the ripening
      process of this cultivar. Ethylene production in Acaua fruits may not be
      sufficient to inactivate the CaETR4-like levels and thus ripening changes occur
      in a slower pace. Thus, the expression analysis of the ethylene biosynthesis and
      signaling genes suggests that ethylene is directly involved in the determination
      of the ripening time of coffee fruits, and CaACO1-like, CaACO4-like and CaETR4
      like may display essential roles during coffee fruit ripening. 

PMID- 24435498
TI  - Gender differences in career paths in psychiatry.
AB  - Although psychiatry has one of the highest proportions of women entering its
      residency programs, women have not assumed a proportionate amount of academic or
      research leadership positions in the field. This literature review identifies
      three general groups of models that explain disparities between men's and women's
      careers, but these do not fully account for observed differences in psychiatric
      practice and academic progression of women in psychiatry. Gender differences in
      career paths in psychiatry are not only affected by individual traits and
      choices, but also by economic factors. Theories based on organizational
      discrimination, and systems and market factors are also reviewed. No single
      explanatory model accounts for disparities between the careers of men and those
      of women. Because psychiatric practice patterns may be broadly distributed across
      labor sectors, more diverse career patterns are possible in psychiatry than in
      more constrained and traditional fields. Research on gender differences in
      psychiatry careers must consider not only the individual work style and choice,
      but also the position of individuals within the organization and the position of
      those organizations across the labor market. 

PMID- 24435499
TI  - What components should be evaluated in a psychiatry residency.
AB  - In this pilot study, the authors examined faculty responses to a proposed new
      evaluation form for residents. Because past research on priorities for
      psychiatric residency curricula have depended on direct surveys, previous
      findings may represent auricular ideals instead of what faculty actually
      evaluate. The goal of the study was to draw inferences about priorities in
      psychiatric education by studying what components (knowledge, skills, and
      attitudes) of a psychiatry residency that faculty are willing to spend their time
      evaluating. The responses were grouped by agreement about whether the item 1)
      could be evaluated on their site, 2) could be evaluated during psychotherapy
      supervision, 3) should be combined with other items, and 4) should be eliminated.
      The results showed much agreement about which items to include and little
      agreement about which ones to exclude. Fundamental psychiatric skills and
      attitudes were rated as most important, and there was widespread interest in a
      diversity of knowledge, skills, and attitudes that psychiatric residents should
      possess. The authors found this method, which could be easily applied to other
      programs, useful in setting auricular priorities. 

PMID- 24435500
TI  - An emerging consensus in behavioral science course content.
AB  - The results of a survey of North American medical schools (N = 65) about the
      content of their behavioral science courses are presented. Child psychological
      development and psychodynamic theory are the most frequently taught subjects in
      the schools (for 94% and 88% of the programs, respectively). Greater agreement on
      topics is found than in earlier surveys. The historical reasons for disagreement
      on content and objectives are explored and proposals for reform are offered. 

PMID- 24435501
TI  - The literature and medicine seminar for medical students : a potential
      recruitment tool.
AB  - Literature and medicine (L-M) seminars have been used occasionally in psychiatric
      training programs, and their use has been sparingly described in the literature.
      A similar seminar designed for preclinical medical students, employing short
      stories focused on medically related themes, was offered as an elective in 1991.
      By asking enrollees about their future specialty choices, the author found that
      the L-M seminar predominantly attracted those students who were drawn to the
      "patient-oriented" specialties. In addition, both psychiatric expertise and
      sensitivity to student concerns and interests were necessary for the seminar to
      succeed. It is proposed, therefore, that the L-M seminar provides a novel
      opportunity for psychiatric educators to attract and encourage patient-oriented
      students to consider psychiatry as a future specialty choice early in their
      training. 

PMID- 24435503
TI  - Frequently asked questions about education in child and adolescent psychiatry.

PMID- 24435502
TI  - Assessing the effectiveness of psychiatric residency training.

PMID- 24435505
TI  - Early experience and multisensory perceptual narrowing.
AB  - Perceptual narrowing reflects the effects of early experience and contributes in
      key ways to perceptual and cognitive development. Previous studies have found
      that unisensory perceptual sensitivity in young infants is broadly tuned such
      that they can discriminate native as well as non-native sensory inputs but that
      it is more narrowly tuned in older infants such that they only respond to native
      inputs. Recently, my coworkers and I discovered that multisensory perceptual
      sensitivity narrows as well. The present article reviews this new evidence in the
      general context of multisensory perceptual development and the effects of early
      experience. Together, the evidence on unisensory and multisensory narrowing shows
      that early experience shapes the emergence of perceptual specialization and
      expertise.

PMID- 24435507
TI  - Comparison of oral ibuprofen with oral indomethacin for PDA closure in Indian
      preterm neonates: a randomized controlled trial.
AB  - Oral ibuprofen is being used as an alternative to indomethacin in medical
      management of patent ductus arteriosus (PDA), but limited data exist on oral
      efficacy of these drugs for PDA closure in India. To assess and compare the
      efficacy of oral ibuprofen and oral indomethacin for PDA closure in preterm
      Indian neonates, we designed a randomized controlled study on clinically
      diagnosed and echocardiographically confirmed hemodynamically significant PDA in
      preterm neonates. Patients were assigned to receive either oral ibuprofen at a
      dosage of 10, 5, 5 mg/kg every 24 h or three doses of oral indomethacin (0.20
      0.25 mg/kg every 24 h) starting on the third day of life or when diagnosed. A
      second course of ibuprofen/indomethacin was given, if PDA failed to close within
      48 h after the first course. Patients were monitored for complications like
      oliguria, bleeding, necrotizing enterocolitis, intraventricular hemorrhage,
      oxygen dependency, and gastrointestinal side effects. The baseline
      characteristics were comparable in both groups. Of the 83 children enrolled, 57.8
      % received oral ibuprofen and 42.1 % received oral indomethacin. The overall
      closure rate of PDA was 60 and 65.7 % in the ibuprofen and indomethacin groups,
      respectively. Closure rate was significantly higher when the drugs were
      administered at an early postnatal age (<8 days) (83.3 % [p = 0.02] in the
      indomethacin group and 75 % [p = 0.03] in the ibuprofen group) in neonates >28
      weeks (ibuprofen group 66.7 % [p = 0.02]; indomethacin group 65.5 % [p = 0.04])
      and in babies with birth weight >1,000 g (ibuprofen group 62.2 %; indomethacin
      group 70 % [p = 0.04 in both groups]). Complications were similar in both groups.
      The efficacy of both drugs was similar. Poor closure in our study could be
      because of genetic differences in pharmacokinetics of drug metabolism in the
      Indian population. Regimens with higher doses or increased duration of treatment
      may increase the frequency of closure. Studies with larger numbers of subjects
      with evaluation of pharmacokinetic parameters are therefore required.

PMID- 24435506
TI  - Olmesartan vs. ramipril in elderly hypertensive patients: review of data from two
      published randomized, double-blind studies.
AB  - Hypertension is a frequent condition among individuals over 65 years of age
      worldwide and is one of the most important risk factors for cardiovascular (CV)
      disease. Effective drug treatment of elderly hypertensives is usually associated
      with a marked reduction in CV morbidity and mortality. Among the different
      classes of antihypertensive agents, angiotensin receptor blockers (ARBs) and ACE
      inhibitors are supposed to provide the best efficacy in lowering blood pressure
      (BP) and protecting target organ damage while featuring a good tolerability
      profile. However, up to date, few randomized clinical studies have directly
      compared the activity and safety of ARBs and ACE-inhibitors in elderly
      hypertensive patients. Aim of this review of published and unpublished pooled
      data from two recent randomized, double-blind, controlled trials, is to offer a
      comprehensive head-to-head comparison of the antihypertensive efficacy of the ARB
      olmesartan medoxomil vs. the ACE-inhibitor ramipril in a large study population
      including more than 1,400 hypertensive subjects aged 65-89 years with mild-to
      moderate essential hypertension. The efficacy of the two drugs was separately
      evaluated in subgroups of patients classified according to the presence of
      metabolic syndrome, reduced renal function, CV risk level, gender, class of age,
      type of arterial hypertension and previous antihypertensive treatments.
      Olmesartan showed a greater efficacy than ramipril both in terms of clinic BP
      reduction and rate normalization. Olmesartan appeared significantly superior to
      ramipril in providing a more homogeneous and long-lasting 24-h BP control and
      maintaining an effective antihypertensive action in the last 6-h period from drug
      intake. In subgroups of patients with additional clinical conditions, olmesartan
      gave comparable, and in some cases greater, BP responses than those achieved with
      the ACE-inhibitor. The incidence of adverse events was similar for both drugs.
      Olmesartan may thus represent an effective alternative to ACE-inhibitors among
      first-line drug treatments for hypertension in older people. 

PMID- 24435508
TI  - Swelling affecting the left inferior labial mucosa. Granulomatous reaction to
      cosmetic lip injection.

PMID- 24435509
TI  - The stress-buffering effects of hope on adjustment to multiple sclerosis.
AB  - BACKGROUND: Hope is an important resource for coping with chronic illness;
      however, the role of hope in adjusting to multiple sclerosis (MS) has been
      neglected, and the mechanisms by which hope exerts beneficial impacts are not
      well understood. PURPOSE: This study aims to examine the direct and stress
      moderating effects of dispositional hope and its components (agency and pathways)
      on adjustment to MS. METHOD: A total of 296 people with MS completed
      questionnaires at time 1 at 12 months later and time 2. Focal predictors were
      stress, hope, agency and pathways, and the adjustment outcomes were anxiety,
      depression, positive affect, positive states of mind and life satisfaction.
      RESULTS: Results of regression analyses showed that as predicted, greater hope
      was associated with better adjustment after controlling for the effects of time 1
      adjustment and relevant demographics and illness variables. However, these direct
      effects of hope were subsumed by stress-buffering effects. Regarding the hope
      components, the beneficial impacts of agency emerged via a direct effects
      mechanism, whereas the effects of pathways were evidenced via a moderating
      mechanism. CONCLUSION: Findings highlight hope as an important protective coping
      resource for coping with MS and accentuate the roles of both agency and pathways
      thinking and their different modes of influence in this process.

PMID- 24435510
TI  - Implication of the human Binder of SPerm Homolog 1 (BSPH1) protein in
      capacitation.
AB  - Binder of SPerm (BSP) proteins are a family of proteins expressed exclusively in
      the male reproductive tract (seminal vesicles or epididymis) of several mammalian
      species. They are known to promote capacitation, a sperm maturation step
      essential for fertilization. Our recent studies have shown that in human, the
      Binder of SPerm Homolog 1 (BSPH1) is expressed solely in epididymal tissues. The
      goal of the current study was to characterize BSPH1 and evaluate its effect on
      different sperm functions. A human recombinant BSPH1 (rec-BSPH1) was produced,
      purified and refolded. Rec-BSPH1 was found to share many characteristics with
      other members of the BSP superfamily, as it was able to bind gelatin and heparin
      as well as capacitate sperm. Rec-BSPH1 had no effect on sperm acrosome reaction
      or any sperm motility parameters. Native BSPH1 was localized on the equatorial
      segment, post-acrosomal segment and neck of ejaculated human sperm. Rec-BSPH1,
      following incubation with washed ejaculated human sperm, exhibited binding
      patterns similar to the native protein. These results show that the human
      epididymal BSPH1 shares many biochemical and functional characteristics with BSP
      proteins secreted by seminal vesicles of ungulates, and behaves similarly to its
      murine epididymal orthologue BSPH1. This study of human BSPH1 brings us one step
      closer to understanding the importance of this protein in male fertility. 

PMID- 24435511
TI  - Intensity modulated radiotherapy induces pro-inflammatory and pro-survival
      responses in prostate cancer patients.
AB  - Intensity modulated radiotherapy (IMRT) is one of the modern conformal
      radiotherapies that is widely used within the context of cancer patient
      treatment. It uses multiple radiation beams targeted to the tumor, however, large
      volumes of the body receive low doses of irradiation. Using gamma-H2AX and global
      genome expression analysis, we studied the biological responses induced by low
      doses of ionizing radiation in prostate cancer patients following IMRT. By means
      of different bioinformatics analyses, we report that IMRT induced an inflammatory
      response via the induction of viral, adaptive, and innate immune signaling. In
      response to growth factors and immune-stimulatory signaling, positive regulation
      in the progression of cell cycle and DNA replication were induced. This denotes
      pro-inflammatory and pro-survival responses. Furthermore, double strand DNA
      breaks were induced in every patient 30 min after the treatment and remaining DNA
      repair and damage signaling continued after 18-24 h. Nine genes belonging to
      inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4,
      SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were
      confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment
      of health effects from the out-of-field low doses during IMRT should be of
      concern, as these may increase the risk of secondary cancers and/or systemic
      inflammation.

PMID- 24435512
TI  - Synthesis of macrolactam analogues of radicicol and their binding to heat shock
      protein Hsp90.
AB  - A series of macrolactam analogues of the naturally occurring resorcylic acid
      lactone radicicol have been synthesised from methyl orsellinate in 7 steps,
      involving chlorination, protection of the two phenolic groups, and hydrolysis to
      the benzoic acid. Formation of the dianion and quenching with a Weinreb amide
      results in acylation of the toluene methyl group that is followed by amide
      formation and ring closing metathesis to form the macrocyclic lactam. Final
      deprotection of the phenolic groups gives the desired macrolactams whose binding
      to the N-terminal domain of yeast Hsp90 was studied by isothermal titration
      calorimetry and protein X-ray crystallography. 

PMID- 24435513
TI  - Orphan drugs policies: a suitable case for treatment.
AB  - CONTEXT: Current orphan drug policies are unsatisfactory when viewed from almost
      all perspectives. Patients find that, although therapies are available for many
      rare conditions, access to care is sometimes restricted. Pharmaceutical
      manufacturers have responded to the incentives for research embodied in orphan
      drug legislation, only to find that funds are not made available to pay for
      therapies once developed. Those funding health care find that most orphan drugs
      do not justify funding based on standard value for money criteria, yet that they
      face political problems if they fail to provide funding for therapy. METHODS: A
      literature review was conducted in order to determine the precise nature of the
      problems and to suggest potential solutions. RESULTS: Current orphan drug
      policies are not fit for the purpose and initiatives need to be taken in the
      areas of (1) clarifying society's views about the priority to be given to orphan
      drugs, (2) revising the arrangements for pricing and reimbursement of orphan
      drugs, (3) defining the priorities for research into rare diseases and (4)
      developing 'joined up' policies to deal with these issues. CONCLUSIONS: Without
      changes in the current policies, pharmaceutical companies will eventually cease
      responding to the incentives to develop orphan drugs, because they will
      increasingly be uncertain whether the drugs, if developed, will be reimbursed.

PMID- 24435514
TI  - Comparison of gastric vascular anatomy by monochromatic and polychromatic dual
      energy spectral computed tomography imaging.
AB  - OBJECTIVE: To evaluate the use of monochromatic and polychromatic dual-energy
      spectral computed tomography (CT) imaging for preoperative assessment of gastric
      vascular anatomy. METHODS: Patients with suspected gastric cancer underwent
      spectral CT to generate conventional 140  kVp polychromatic and monochromatic
      images with energy levels ranging from 40 to 140  keV during the late arterial
      and portal venous phases. Optimal monochromatic images were selected according to
      the contrast-to-noise ratio (CNR) for the gastric artery. Image quality was
      subjectively assessed. Display rates of the arteries were recorded. RESULTS: The
      study included 64 patients. Monochromatic images at 53 +/- 3  keV provided the
      optimum CNR. At this energy level, subjective image scores were significantly
      higher for monochromatic images than polychromatic images. There were no
      significant differences in the display rates of arteries between polychromatic
      and optimal monochromatic images. CONCLUSIONS: Monochromatic images obtained with
      spectral CT can improve the visualization of gastric arteries.

PMID- 24435515
TI  - RNA granule component TDRD7 gene polymorphisms in a Han Chinese population with
      age-related cataract.
AB  - OBJECTIVES: To examine whether polymorphisms in the RNA granule component tudor
      domain-containing protein 7 (TDRD7) gene are associated with susceptibility to
      age-related cataract (ARC) in a Han Chinese population. METHODS: Patients with
      ARC, and age-, sex- and ethnically-matched healthy control subjects were enrolled
      in the study. Five single nucleotide polymorphisms (SNPs) within the TDRD7 gene,
      rs1462091, rs11793735, rs10981985, rs2045732 and rs1462089, were genotyped using
      a SNaPshot(r) Multiplex Kit. RESULTS: The study included 271 control subjects and
      218 patients with ARC. The rs10981985 SNP was associated with ARC in dominant
      (odds ratio [OR] 0.561, 95% confidence interval [CI] 0.388, 0.809) and allele
      dose (OR 0.619, 95% CI 0.455, 0.841) genetic models. The rs10981985 A allele
      frequency was lower in patients with cortical ARC than in control subjects (OR
      0.502, 95% CI 0.315, 0.801). The rs10981985 polymorphism was significantly
      associated with cortical ARC in a dominant genetic model (OR 0.431, 95% CI 0.251,
      0.740). CONCLUSIONS: The present study suggests that the rs10981985 G -> A
      variant within the TDRD7 gene may protect against cortical ARC in a Han Chinese
      population.

PMID- 24435516
TI  - Long-term improvements in pulmonary function 5 years after bariatric surgery.
AB  - BACKGROUND: Obesity is associated with reduced pulmonary function. We evaluated
      pulmonary function and status of asthma and obstructive sleep apnoea syndrome
      (OSAS) before and 5 years after bariatric surgery. METHODS: Spirometry was
      performed at baseline and 5 years postoperatively. Information of asthma and OSAS
      were recorded. Of 113 patients included, 101 had undergone gastric bypass, 10
      duodenal switch and 2 sleeve gastrectomy. RESULTS: Eighty (71%) patients were
      women, mean preoperative age was 40 years and preoperative weight was 133 kg in
      women and 158 kg in men. Five years postoperatively, weight reduction was 31% (42
      kg; p < 0.001) in women and 24% (38 kg; p < 0.001) in men. Forced expiratory
      volume in 1 s (FEV1) increased 4.1% (116 ml; p < 0.001) in women and 6.7% (238
      ml; p = 0.003) in men. Forced vital capacity (FVC) increased 5.8% (209 ml; p <
      0.001) in women and 7.6% (349 ml; p < 0.001) in men. Gender and weight loss were
      independently associated with the improvements in FEV1 and FVC. At follow-up,
      FEV1 had increased 36% of the difference towards the estimated normal FEV1, and
      there was a corresponding 70% recovery of FVC. These improvements occurred
      despite an expected decline in pulmonary function by age during the study period.
      Of the asthmatics and OSAS patients, 48 and 80%, respectively, were without
      symptoms 5 years postoperatively. CONCLUSIONS: Pulmonary function measured with
      spirometry was significantly improved 5 years after bariatric surgery, despite an
      expected age-related decline during this period. Symptoms of asthma and OSAS also
      improved.

PMID- 24435518
TI  - [Competition between haploid cells in the ovary of Oenothera].
AB  - Investigations were made on the segregation of the genes s, de and of the
      translocation point of the first linkage-group in the progeny of backcrosses of
      heterozygotes of Oenothera with the complexes (h) hookeri and flavens with Oe.
      hookeri sulfurea ?. The deviations from mendelian expectation are statistically
      significant. The phenotype corresponding to the hookeri-parent of the F1 occurs
      with the greatest relative frequency.An interpretation of the results is given on
      the assumption that in the first linkage group, which appears cytologically as a
      translocation group of four chromosomes, a gene with gametophytic action is
      located. The complex (h) hookeri contains the allel ga-?(+), the complex flavens
      ga-?(-). These alleles influence the development of the haploid cells in the
      ovary in such a way that in a heterozygote mother plant the haploid cells with
      the allel ga-?(+) have a greater chance to form the embryosac and the egg cell
      than haploid cells with the allel ga-?(-).There is a strong negative interference
      in the parts of the chromosomes adjacent to the translocation point.The
      variability of the recombination of the three loci leads to the assumption of
      highly variable crossover-values in the chromosomes here investigated. A
      correlation between this variability of crossing-over and of the negative
      interference with pairing anomalies in a translocation group is taken into
      consideration.Hypotheses concerning the genetic basis of the competition between
      haploid cells in the ovary and the anther and the action of these gametophytic
      genes are discussed. 

PMID- 24435517
TI  - Changes in bone mineral density after sleeve gastrectomy or gastric bypass:
      relationships with variations in vitamin D, ghrelin, and adiponectin levels.
AB  - BACKGROUND: A major long-term concern after gastric bypass (GBP) is the risk of
      osteoporosis; however, little is known about this complication in patients
      undergoing sleeve gastrectomy (SG). OBJECTIVE: To evaluate changes in bone
      mineral density (BMD) after GBP and SG, and its relationship with changes in
      vitamin D, parathyroid hormone (PTH), ghrelin, and adiponectin. METHODS: Twenty
      three women undergoing GBP (BMI 42.0 +/- 4.2 kg/m2; 37.3 +/- 8.1 years) and 20
      undergoing SG (BMI 37.3 +/- 3.2 kg/m2; 34.2 +/- 10.2 years) were studied before
      and 6 and 12 months after surgery. BMD was measured by dual-energy X-ray
      absorptiometry. Plasma PTH, 25-hydroxyvitamin D (25-OHD), ghrelin, and
      adiponectin concentrations were determined. Food as well as calcium and vitamin D
      supplement intake was recorded. RESULTS: Excess weight loss (mean +/- SE),
      adjusted by baseline excess weight, was 79.1+/-3.8% and 74.9 +/- 4.1% 1 year
      after GBP and SG, respectively (p = 0.481). Significant reduction in BMD for
      total body (TB), lumbar spine (LS), and femoral neck (FN) was observed after GBP.
      In the SG group, reduction in BMD was significant only for TB. Adjusted by
      baseline BMD, the difference between change in BMD for GBP vs. SG was not
      significant for TB, LS, or FN. Percent reduction in ghrelin concentration was a
      main factor related to total BMD loss (GBP group) and LS BMD loss (GBP and SG
      groups). CONCLUSIONS: One year after gastric bypass, bone mineral density was
      significantly affected, mainly at the femoral neck. Decreases in bone mineral
      density were more dramatic among patients who had greater baseline BMD and
      greater reduction in ghrelin concentrations.

PMID- 24435519
TI  - Comparison of growth functions within and between lines of mice selected for
      large and small body weight.
AB  - Several criteria have been suggested for comparing different nonlinear growth
      functions to determine which function gives the best quantitative description of
      a given set of observed sigmoid growth curves. These criteria were then used to
      compare the logistic, Gompertz and Bertalanffy functions within and among lines
      of mice: a control line (C 1) and lines selected for large (H 6) and small (L 6)
      body weight at six weeks of age.A general comparison of the three growth
      functions was based on the differences in residual variances of the respective
      functions fitted to the growth data of individual mice. Since the three functions
      differ primarily in the fixed proportion of the asymptotic weight at which the
      inflexion point occurs, the growth function which will provide the minimum
      residual variance among the three considered is the one which most closely
      approximates the observed proportion. The results of this comparison indicated
      that the logistic function gave the best fit for both sexes of the H 6 and C 1
      lines. While no significant differences in residual variances were evident in L 6
      males, the Bertalanffy function had the smallest residual variance in L 6
      females.The four derived traits of each growth function analyzed individually
      were the asymptote (A), age at inflexion (t (*)), rate at which a logarithmic
      function of body weight changes with time (k) and mean absolute growth rate with
      respect to body weight increase (v). The coefficient of variation among
      individuals within full-sib families was used to compare the relative variability
      of the analogous traits estimated from the three growth functions. The
      coefficients of variation of A, t (*) and k calculated from the logistic function
      were significantly (P < .01) smaller than those from both the Gompertz and
      Bertalanffy functions in all three lines, while there were no significant
      differences in the relative variability of v among the three lines. The genetic
      and phenotypic correlations between the analogous traits estimated from two
      different growth functions were sufficiently high in most cases to conclude that
      the same trait was being measured by the three growth functions. Each derived
      trait was analyzed for variation in lines, sexes, seasons and respective
      interactions. The sources of variation generally exhibited similar levels of
      significance for the analogous traits estimated by the three functions, although
      a few exceptions were found. These results suggest that although the logistic
      function provided the best description of the growth data, the same general
      conclusions about differences within and among the three lines would have been
      reached with any of the three functions. The four derived traits of the logistic
      curve were used to describe quantitatively the differences in growth among the H
      6, L 6 and C 1 lines. 

PMID- 24435520
TI  - [Experiments on male-sterility of sun-flowers, caused by genetical, physiological
      and applied chemical factors].
AB  - 1. Male-sterile plants could be selected for several generations. These produce
      by sib mating (malesterile x fertile) 50% male-sterile and 50% fully fertile
      descendants. In two cases crossing resulted in 75% malesterile plants in F1. 2.
      Two new varieties, which had originated from a combination of breeding by self
      pollinations and by multiple crossings and which show earlier flowering under
      shorter photoperiods than do other varieties, were sawn in July 1966 and 1967.
      Flowering began at the end of September and in the beginning of October, there
      was found an 80-100% male-sterility (retrogressive antheres). Varieties which
      react less to short day treatment had complete fertile flowers. 3. Experiments
      which were started some years earlier to induce male-sterility of sun-flowers by
      active substances brought the following results in 1963-1967: a) Gibberellic acid
      treatment (0.5-0.25 mg/plant) applied at the beginning of bud formation, induced
      malesterility. In this way it is possible to produce small quantities of hybrid
      seed and to test topcrosses. b) Some combinations of gibberellic acid with other
      active substances, e.g. 0.25 mg gibb. ac. + 0.25 mg TJBS, 0.25 mg gibb. ac. + 0.1
      mg NES, 0.25 mg gibb. ac. + 0.1 mg IES and 0.25 mg gibb. ac. + 0.5 mg CCC induced
      malesterility but permitted sufficient female fertility. c) At a male-sterility
      of 90-100% total average fertility of 10 plants was only 25-75%. In treating 87
      plants of the inbred line 'HEBH' a production of kernels ranging from 0 to 86%
      was found, 39% on the average, that is 202 kernels/flower, as compared to 90% for
      untreated plants. d) Varieties and inbred lines show different reactions to the
      treatment. There are also marked differences in effects of active substances
      under different climatic conditions, which makes the practical application of
      treatments difficult. It therefore becomes necessary to test different varieties
      for reaction to active substances or to combinations of these substances under
      different climatic conditions. 

PMID- 24435521
TI  - The pachytene chromosomes of Ipomoea crassicaulis.
AB  - The detailed morphology of the pachytene chromosomes and microsporogenesis have
      been studied in a diploid (2 n=30) American species, Ipomoea crassicaulis (Bth)
      B. L. Robinson. Idiogram of the pachytene chromosomes is presented and taking
      advantage of the extreme precision that pachytene analysis can lend, karyological
      characteristics of the haploid complement have been worked out in detail and
      individual chromosomes are identified. The course of meiosis was normal and over
      ninety five percent of pollen were found stainable. The urgent need for extending
      similar studies to other taxa in this economically important genus for
      unravelling phyletic relationships has been stressed. 

PMID- 24435522
TI  - Some factors in the distribution of European pine sawfly egg clusters in an
      experimental plantation of hard pines.
AB  - 1. During three successive years the frequencies of oviposition by Neodiprion
      sertifer (Hymenoptera: Diprionidae) were observed in 546 pines (provenances of
      various hard pine species, hybrids between such species, and some white pines).
      The insects were able to discriminate between 30 host genotypes since in this
      preference test average oviposition frequency varied between genotypes. 2.
      Oviposition frequencies had to be inferred to from groups of feeding larvae. 3.
      Besides genotype, four other groups of variables had an effect on the number of
      larval colonies: position of a tre in the plantation (in terms of rows and
      columns), its dimensions, the dimensions of its neighbors, and the number o
      colonies in the neighbors. 4. Apparently different crown portions were preferred
      oviposition sites in the various genotypes. 5. Water potentials of a sample of
      host trees during the hatching period showed no relations to susceptibility. 

PMID- 24435523
TI  - Better staff engagement improves NHS care, says report.

PMID- 24435524
TI  - Novartis faces charges in Japan over promotion of valsartan to doctors.

PMID- 24435525
TI  - 5,5'-Bis-(trinitromethyl)-3,3'-bi-(1,2,4-oxadiazole): a stable ternary CNO
      compound with high density.
AB  - 5,5'-Bis-(trinitromethyl)-3,3'-bi-(1,2,4-oxadiazole) is a new ternary CNO
      compound. It has been synthesized by nitration of diammonium 5,5'-bis
      (dinitromethanide)-3,3'-bi-(1,2,4-oxadiazole) with nitronium tetrafluoroborate.
      Single crystal X-ray diffraction studies show a remarkable high density. Thermal
      stability and sensitivities of the new compound were determined by differential
      scanning calorimetry (DSC) and standardized drop hammer and friction tests. 

PMID- 24435526
TI  - Improvement in angiogenesis and osteogenesis with modified cannulated screws
      combined with VEGF/PLGA/fibrin glue in femoral neck fractures.
AB  - Angiogenesis is essential for bone healing. Vascular endothelial growth factor
      (VEGF) is regarded as one of the most potent antigenic cytokines; however, there
      have been very few studies that have previously investigated the effects of VEGF
      on bone healing in a femoral neck fracture model. Thus, the aim of the present
      study was to test both the angiogenic and osteogenic properties of a VEGF/poly
      lactic acid glycolic acid (PLGA) delivery system for the treatment of femoral
      neck fractures. VEGF/PLGA microspheres were prepared by the double emulsion
      solvent-evaporation method and in vitro VEGF release was quantified by an ELISA
      assay. Then the preparation of femoral neck fracture model and internal fixation
      were performed, and the effect of the VEGF/PLGA microspheres on bone healing was
      determined by X-ray, radionuclide bone scanning, and histomorphometric
      evaluation. The release of VEGF from the VEGF/PLGA microspheres was sustained for
      at least 42 days in vitro, and suspension of the delivery system in fibrin glue
      further slowed this VEGF release rate. In dogs, revascularization of the
      fractured femoral heads was significantly improved by a local injection of
      VEGF/PLGA/fibrin glue, and the quality and speed of fracture healing were
      significantly improved in the Experimental group than in the Control group. Our
      study confirmed that the VEGF/PLGA delivery system offers good angiogenic and
      osteogenic properties for the treatment of canine femoral neck fractures.

PMID- 24435527
TI  - New urethane oligodimethacrylates with quaternary alkylammonium for formulating
      dental composites.
AB  - The aim of this study was to prepare urethane dimethacrylates containing
      quaternary alkyl (C16, C12) ammonium and polyethylene glycol short sequences (Mn,
      400 g/mol) and to investigate their behaviour in some experimental formulations
      in order to evaluate their potential applicability in the dental composites
      field. The structure of urethane dimethacrylates has been confirmed by (1)H
      ((13)C) NMR and FTIR spectra, as well as by electrospray ionization tandem mass
      spectroscopy, and gel permeation chromatography measurements. The effects of the
      cationic macromers on the properties of the filled/non-filled composites were
      examined through FTIR, photoDSC, and specific measurements as volumetric
      polymerization shrinkage, water sorption/solubility, contact angle, mechanical
      parameters, and morphology. The monomer compositions based on cationic
      dimethacrylate (6.88-27.52 wt%), BisGMA-analogue (48.18-68.82 wt%) and TEGDMA
      (23.3 wt%) showed a good photoreactivity in terms of double bond conversion (DC,
      50.07-68.81 %) and polymerization rate (Rp, 0.099-0.141 s(-1)) measured by
      photoDSC compared to a control sample (BisGMA-1/TEGDMA: DC, 45.91 %; Rp, 0.162 s(
      1)), while the polymerization shrinkage increased in acceptable limits (5.37-7.74
      vol%). The mechanical properties (compressive, flexural and diametral tensile
      strength) of the composite resin incorporating 70 wt% silanized zirconium
      silicate micro/nanopowder can be modulated by the initial co-monomer
      concentrations.

PMID- 24435529
TI  - Perspectives on screening and interviewing international medical graduates for
      psychiatric residency training programs.
AB  - The authors have found that international medical graduates (IMGs) constitute a
      valuable pool of applicants for residency training. The wide variation in their
      medical educations, prior careers, and cultural backgrounds requires a special
      approach to screening and interviewing IMGs. The authors share techniques and
      viewpoints developed in their program to screen applicants about their
      autobiographical statements, medical credentials, reference letters, and visa and
      immigration statuses. Interviewing guidelines that are sensitive to the
      applicant's career phase and that assess the person's interest in psychiatry,
      communication skills, character, acculturation, family context, and suitability
      for the specific residency program are presented. 

PMID- 24435528
TI  - Degradable borate glass polyalkenoate cements.
AB  - Glass polyalkenoate cements (GPCs) containing aluminum-free borate glasses having
      the general composition Ag2O-Na2O-CaO-SrO-ZnO-TiO2-B2O3 were evaluated in this
      work. An initial screening study of sixteen compositions was used to identify
      regions of glass formation and cement compositions with promising rheological
      properties. The results of the screening study were used to develop four model
      borate glass compositions for further study. A second round of rheological
      experiments was used to identify a preferred GPC formulation for each model glass
      composition. The model borate glasses containing higher levels of TiO2 (7.5 mol
      %) tended to have longer working times and shorter setting times. Dissolution
      behavior of the four model GPC formulations was evaluated by measuring ion
      release profiles as a function of time. All four GPC formulations showed evidence
      of incongruent dissolution behavior when considering the relative release
      profiles of sodium and boron, although the exact dissolution profile of the glass
      was presumably obscured by the polymeric cement matrix. Compression testing was
      undertaken to evaluate cement strength over time during immersion in water. The
      cements containing the borate glass with 7.5 mol % TiO2 had the highest initial
      compressive strength, ranging between 20 and 30 MPa. No beneficial aging effect
      was observed-instead, the strength of all four model GPC formulations was found
      to degrade with time.

PMID- 24435530
TI  - Psychiatric resident moonlighting : a review and modest proposal.
AB  - Moonlighting by psychiatric residents remains controversial, with debate
      surrounding the ethical, legal, financial, and educational risks involved in the
      practice. The authors present a literature review of resident moonlighting, which
      encompasses the policy positions of various organizations responsible for
      graduate medical education; surveys of various groups and specialties regarding
      the prevalence, form, and justification for moonlighting; and models of
      moonlighting programs in several institutions. The authors conclude with specific
      proposals for research regarding psychiatric resident moonlighting and, more
      importantly, emphasize the need for research on the effects of moonlighting on
      resident performance and education. 

PMID- 24435531
TI  - A survival guide for aspiring academic psychiatrists : personality attributes and
      opportunities for academic success.
AB  - Many residents in psychiatric residency training are interested in an "academic
      career" Recognizing that current academic departments require excellent teachers,
      clinicians, and administrators in addition to researchers, medical schools and
      their universities are wrestling with titles and tenure as they attempt to
      provide opportunities via a variety of academic career paths. What constitutes
      the most suitable career path for the academic aspirant depends on the person's
      goals, motivations, interests, values, personality style, talents, background,
      and training, as well as historically and geographically available training,
      mentoring, and employment opportunities. The authors examine alternative
      definitions of "academic success," relate these to the variety of personality
      types and opportunities found in academic settings, and provide some guidelines
      for advancement along the available career paths. 

PMID- 24435532
TI  - Teaching psychiatry through literature : the short story as case history.
AB  - The author proposes a simple systematic way to analyze short stories as if they
      were case histories. Class discussions are organized around five basic questions,
      stated in the article, and use Erikson's framework of life stages to translate
      life experiences into the language of psychic conflict. Fiction writers
      effectively dramatize psychological and developmental issues in a way that makes
      them real and memorable to psychiatric residents. Stories may be of particular
      value in illustrating the process of change and in exploring the topic of
      prognosis, which are often overlooked in more traditional teaching formats. The
      author has presented this approach at several recent meetings of the American
      Association of Directors of Psychiatric Residency Training and the American
      Academy of Child and Adolescent Psychiatry, and workshop participants have
      reported success in its use, which depends on the teacher's clinical rather than
      literary skills. 

PMID- 24435534
TI  - Discussing ethnic diversity with medical students: a pilot program.

PMID- 24435535
TI  - Symbols, systeme international (SI) units, abbreviations, conversion factors and
      special instructions to be used in photosynthesis research.

PMID- 24435536
TI  - Diurnal and seasonal patterns of net photosynthesis by irrigated Chrysothamnus
      nauseosus under field conditions.
AB  - Chrysothamnus nauseosus ssp. albicaulis (white rubber rabbitbrush) is a common
      deciduous C3 desert shrub which is a potential source of natural rubber and which
      exhibits high rates of net photosynthesis (Pn) for a woody species. When
      maintained under irrigated conditions in the field, rates of Pn on cloudless days
      were generally found to be highest during the cool morning hours (peak rates
      observed between about 0900 and 1000 hrs). Pn declined during mid-day hours and
      was approximately 75% of that observed in the early morning for the remainder of
      the light period. This decline in Pn was accompanied by about 26 MUmol CO2.m(
      2).s(-1) in mid-May (approximately 30 days after bud break) to about 48 MUmol
      CO2.m(-2).s(-1) in early August. Thereafter, Pn declined gradually until leaf
      fall in November. These data indicate that rabbitbrush is capable of relatively
      high rates of Pn throughout a substantial portion of the growing season when
      maintained under irrigated conditions. This may, at least in part, account for
      the relatively high rates of growth observed under conditions of ample soil
      moisture. 

PMID- 24435537
TI  - Chlorophyll-protein complex composition during chloroplast development: A species
      comparison.
AB  - Barley, maize, pea, soybean, and wheat exhibited differences in chlorophyll a/b
      ratio and chlorophyll-protein (CP) complex composition during the initial stages
      of chloroplast development. During the first hours of greening, the chlorophyll
      a/b ratios of barley, pea, and wheat were high (a/b>=8) and these species
      contained only the CP complex of photosystem I as measured by mild sodium dodecyl
      sulfate polyacrylamide gel electrophoresis. A decrease in chlorophyll a/b ratio
      and the observation of the CP complexes associated with photosystem II and the
      light-harvesting apparatus occurred at later times in barley, pea, and wheat. In
      contrast, maize and soybean exhibited low chlorophyll a/b ratios (a/b<8) and
      contained the CP complexes of both photosytem I and the light-harvesting
      apparatus at early times during chloroplast development. The species differences
      were not apparent after 8 h of greening. In all species, the CP complexes were
      stabilized during the later stages of chloroplast development as indicated by a
      decrease in the percentage of chlorophyll released from the CP complexes during
      detergent extraction. The results demonstrate that CP complex synthesis and
      accumulation during chloroplast development may not be regulated in the same way
      in all higher plant species. 

PMID- 24435538
TI  - Large scale preparation of pure phycobiliproteins.
AB  - This paper describes simple procedures for the purification of large amounts of
      phycocyanin and allophycocyanin from the cyanobacterium Microcystis aeruginosa. A
      homogeneous natural bloom of this organism provided hundreds of kilograms of
      cells. Large samples of cells were broken by freezing and thawing. Repeated
      extraction of the broken cells with distilled water released phycocyanin first,
      then allophycocyanin, and provides supporting evidence for the current models of
      phycobilisome structure. The very low ionic strength of the aqueous extracts
      allowed allophycocyanin release in a particulate form so that this protein could
      be easily concentrated by centrifugation. Other proteins in the extract were
      enriched and concentrated by large scale membrane filtration. The biliproteins
      were purified to homogeneity by chromatography on DEAE cellulose. Purity was
      established by HPLC and by N-terminal amino acid sequence analysis. The proteins
      were examined for stability at various pHs and exposures to visible light. 

PMID- 24435539
TI  - Crassulacean acid metabolism, CO2-recycling, and tissue desiccation in the
      Mexican epiphyte Tillandsia schiedeana Steud (Bromeliaceae).
AB  - After 23 days without water in a greenhouse, rates of nocturnal CO2 uptake in
      Tillandsia schiedeana decreased substantially and maximum rates occurred later in
      the dark period eventually coinciding with the onset of illumination. Nocturnal
      CO2 uptake accounted for less than half the total nighttime increase in acidity
      measured in well-watered plants. With increased tissue desiccation, only 11-12%
      of measured acid accumulation was attributable to atmospheric CO2 uptake. Plants
      desiccated for 30 days regained initial levels of nocturnal acid accumulation and
      CO2 uptake after rehydration for 10h. These results stress the importance of CO2
      recycling via CAM in this epiphytic bromeliad, especially during droughts. 

PMID- 24435540
TI  - Net CO2 assimilation of taro and cocoyam as affected by shading and leaf age.
AB  - Taro and cocoyam were grown outdoors in either full sun or under 40% shade.
      Leaves were tagged as they emerged and the effect of leaf age on net CO2
      assimilation rate (A) was determined. The effects of shading on A, transpiration
      (E), stomatal conductance for CO2 (gc) and H2O (gs), and water use efficiency
      (WUE) were also determined for leaves of a single age for each species. The
      effect of leaf age on A was similar for both species. Net CO2 assimilation rates
      increased as leaf age increased up to 28 days with the exception of a sharp
      decline in A for 21 day-old leaves which corresponded to unusually low
      temperatures during the period of leaf expansion. A generally decreased as leaves
      aged beyond 28 days. Cocoyam had higher A rates than taro. Leaves of shade-grown
      plants had higher rates of A and E for both species at photosynthetic photon flux
      densities (PPFD) up to 1600 MUmol s(-1) m(-2). Shade-grown leaves of cocoyam had
      greater leaf dry weights per area (LW/A) and a trend toward higher gc and gs than
      sun-grown leaves. Shade leaves of taro had greater gc and g3 rates than sun-grown
      leaves. The data suggest that taro and cocoyam are highly adapted to moderate
      shade conditions. 

PMID- 24435541
TI  - Photosynthesis and stomatal conductance of potato leaves-effects of leaf age,
      irradiance, and leaf water potential.
AB  - Potatoes (Solanum tuberosum L., cv. Bintje) were grown in a naturally lit
      glasshouse. Laboratory measurements on leaves at three insertion levels showed a
      decline with leaf age in photosynthetic capacity and in stomatal conductance at
      near saturating irradiance. Conductance declined somewhat more with age than
      photosynthesis, resulting in a smaller internal CO2 concentration in older
      relative to younger leaves. Leaves with different insertion number behaved
      similarly. The changes in photosynthesis rate and in nitrogen content with leaf
      age were closely correlated. When PAR exceeded circa 100 W m(-2) the rate of
      photosynthesis and stomatal conductance changed proportionally as indicated by a
      constant internal CO2 concentration. The photosynthesis-irradiance data were
      fitted to an asymptotic exponential model. The parameters of the model are AMAX,
      the rate of photosynthesis at infinite irradiance, and EFF, the slope at low
      light levels. AMAX declined strongly with leaf age, as did EFF, but to a smaller
      extent. During drought stress photosynthetic capacity declined directly with
      decreasing water potential (range -0.6 to -1.1 MPa). Initially, stomatal
      conductance declined faster than photosynthetic capacity. 

PMID- 24435542
TI  - Preparation of a highly active ATPase of the mesophilic cyanobacterium Spirulina
      maxima.
AB  - In this work, we report new studies on the ATPase attached to the photosynthetic
      membranes of the mesophilic cyanobacterium Spirulina maxima. This enzyme does not
      display persistent latency as had been previously reported for the ATPase of
      Spirulina platensis. The enzyme is readily activated by the careful application
      of methods currently used to activate chloroplast CF1. Photosynthetic membranes
      of Spirulina maxima show a Mg(2+)-dependent ATPase activity of 195+/-25 MUmol Pi
      (mg chl)(-1) h(-1) after a light plus dithiothreitol (DDT) treatment. Methanol
      treatment of these membranes elicits Mg(2+)-dependent ATPase activity of 222+/-18
      MUmol Pi (mg chl)(-1) h(-1).Here, we also describe the purification of the
      soluble coupling factor AF1 of Spirulina maxima. This enzyme is unique among
      mesophilic cyanobacterial F1 preparations in regard to its high specific Ca(2+)
      dependent ATPase activity after heat treatment (14.75+/-1.91 MUmol Pi (mg prot)(
      1) min(-1)) and its room temperature stability. 

PMID- 24435543
TI  - Sex differences in the weighting of metric and categorical information in spatial
      location memory.
AB  - According to the Category Adjustment model, remembering a spatial location
      involves the Bayesian combination of fine-grained and categorical information
      about that location, with each cue weighted by its relative certainty. However,
      individuals may differ in terms of their certainty about each cue, resulting in
      estimates that rely more or less on metric or categorical representations. To
      date, though, very little research has examined individual differences in the
      relative weighting of these cues in spatial location memory. Here, we address
      this gap in the literature. Participants were asked to recall point locations in
      uniform geometric shapes and in photographs of complex, natural scenes. Error
      patterns were analyzed for evidence of a sex difference in the relative use of
      metric and categorical information. As predicted, women placed relatively more
      emphasis on categorical cues, while men relied more heavily on metric
      information. Location reproduction tasks showed a similar effect, implying that
      the sex difference arises early in spatial processing, possibly during encoding. 

PMID- 24435544
TI  - Moderate warming in microcosm experiment does not affect microbial communities in
      temperate vineyard soils.
AB  - Changes in the soil microbial community structure can lead to dramatic changes in
      the soil ecosystem. Temperature, which is projected to increase with climate
      change, is commonly assumed to affect microbial communities, but its effects on
      agricultural soils are not fully understood. We collected soil samples from six
      vineyards characterised by a difference of about 2  degrees C in daily soil
      temperature over the year and simulated in a microcosm experiment different
      temperature regimes over a period of 1 year: seasonal fluctuations in soil
      temperature based on the average daily soil temperature measured in the field;
      soil temperature warming (2  degrees C above the normal seasonal temperatures);
      and constant temperatures normally registered in these temperate soils in winter
      (3  degrees C) and in summer (20  degrees C). Changes in the soil bacterial and
      fungal community structures were analysed by automated ribosomal intergenic
      spacer analysis (ARISA). We did not find any effect of warming on soil bacterial
      and fungal communities, while stable temperatures affected the fungal more than
      the bacterial communities, although this effect was soil dependent. The soil
      bacterial community exhibited soil-dependent seasonal fluctuations, while the
      fungal community was mainly stable. Each soil harbours different microbial
      communities that respond differently to seasonal temperature fluctuations;
      therefore, any generalization regarding the effect of climate change on soil
      communities should be made carefully.

PMID- 24435545
TI  - Investigating the link between imipenem resistance and biofilm formation by
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa, a ubiquitous environmental organism, is a difficult-to
      treat opportunistic pathogen due to its broad-spectrum antibiotic resistance and
      its ability to form biofilms. In this study, we investigate the link between
      resistance to a clinically important antibiotic, imipenem, and biofilm formation.
      First, we observed that the laboratory strain P. aeruginosa PAO1 carrying a
      mutation in the oprD gene, which confers resistance to imipenem, showed a modest
      reduction in biofilm formation. We also observed an inverse relationship between
      imipenem resistance and biofilm formation for imipenem-resistant strains selected
      in vitro, as well as for clinical isolates. We identified two clinical isolates
      of P. aeruginosa from the sputum of cystic fibrosis patients that formed robust
      biofilms, but were sensitive to imipenem (MIC <= 2 MUg/ml). To test the
      hypothesis that there is a general link between imipenem resistance and biofilm
      formation, we performed transposon mutagenesis of these two clinical strains to
      identify mutants defective in biofilm formation, and then tested these mutants
      for imipenem resistance. Analysis of the transposon mutants revealed a role for
      previously described biofilm factors in these clinical isolates of P. aeruginosa,
      including mutations in the pilY1, pilX, pilW, algC, and pslI genes, but none of
      the biofilm-deficient mutants became imipenem resistant (MIC >= 8 MUg/ml),
      arguing against a general link between biofilm formation and resistance to
      imipenem. Thus, assessing biofilm formation capabilities of environmental
      isolates is unlikely to serve as a good predictor of imipenem resistance. We also
      discuss our findings in light of the limited literature addressing planktonic
      antibiotic resistance factors that impact biofilm formation.

PMID- 24435547
TI  - Sacrococcygeal cornua as zygapophysial joints.

PMID- 24435546
TI  - Two-year outcomes of electrosurgery and calcium-enriched mixture pulpotomy in
      primary teeth: a randomised clinical trial.
AB  - AIM: The purpose of this prospective split-mouth, randomised clinical trial was
      to assess the clinical and radiographic success rate of pulpotomy in primary
      molars using calcium-enriched mixture (CEM) cement or placement of zinc oxide
      eugenol after electrosurgery (ES/ZOE). METHODS: Pulpotomy was performed for 102
      primary second molars in 51 children aged between 4 and 6 years. Considering a
      split-mouth design, for each patient the right and left second primary molars
      randomly underwent pulpotomy using CEM cement or ES/ZOE. All teeth were restored
      using preformed metal crowns. Following pulpotomy procedure, teeth were blindly
      evaluated for clinical and radiographic success after 6, 12 and 24 months.
      McNemar test and SPSS 16 software were used for the statistical analysis.
      RESULTS: After 24 months, clinical success rates were 100% in both groups,
      however, radiographic success rates of ES/ZOE and CEM were calculated as 95.2 and
      90%, respectively, with no significant difference (p = 0.625). The most common
      radiographic sign of failure was internal resorption. CONCLUSION: The results of
      this investigation show that the treatment success rate with CEM cement was
      similar to the electrosurgical pulpotomy.

PMID- 24435548
TI  - Nasal packing after septoplasty: cardiopulmonary impact.
AB  - IMPORTANCE: Bilateral anterior nasal packing is used after septoplasty with the
      goals of decreasing the risk of postoperative bleeding and adhesions. However,
      multiple studies caution against the use of nasal packing because of the risk of
      cardiopulmonary complications. OBJECTIVE: To evaluate the cardiopulmonary risks
      associated with bilateral anterior nasal packing after septoplasty. EVIDENCE
      REVIEW: A literature review was conducted by 2 independent reviewers using
      EMBASE, Ovid, Medline, PubMed, Google Scholar, Cochrane Central Register of
      Controlled Trials (CENTRAL), and reference list review from January 1966 to
      September 2012 to identify studies assessing nasal packing after septoplasty. The
      studies were reviewed and assigned an Oxford level of evidence grade, Detsky
      score, and Methodological Index for Nonrandomized Studies (MINORS) score. Data
      were extracted for arterial blood gases, oxygen desaturations, oxygen
      saturations, and adverse outcomes. Pooled estimates for randomized studies were
      performed when possible. FINDINGS: Fourteen studies conducted between 1973 and
      2011 were included: 2 randomized clinical trials (RCTs) with a total of 119
      patients and 12 prospective observational studies with a total of 356 patients.
      Nine studies showed a significant change within 1 of the cardiopulmonary
      parameters investigated. However, there was no consistency in changes across both
      observational and randomized studies. Furthermore, pooled estimates for
      cardiopulmonary parameters were all nonsignificant: standard mean differences of
      the pooled results of the RCTs were 0.05 (95% CI, -0.31 to 0.41) for arterial pH,
      0.08 (95% CI, -0.30 to 0.46) for Paco2, and -0.32 (95% CI, -1.28 to 0.63) for
      Pao2. There were no major cardiopulmonary complications after nasal packing.
      CONCLUSIONS AND RELEVANCE: Bilateral anterior nasal packing does not seem to
      cause adverse cardiopulmonary changes after septoplasty.

PMID- 24435549
TI  - Femtosecond laser ablation of highly oriented pyrolytic graphite: a green route
      for large-scale production of porous graphene and graphene quantum dots.
AB  - Porous graphene (PG) and graphene quantum dots (GQDs) are attracting attention
      due to their potential applications in photovoltaics, catalysis, and bio-related
      fields. We present a novel way for mass production of these promising materials.
      The femtosecond laser ablation of highly oriented pyrolytic graphite (HOPG) is
      employed for their synthesis. Porous graphene (PG) layers were found to float at
      the water-air interface, while graphene quantum dots (GQDs) were dispersed in the
      solution. The sheets consist of one to six stacked layers of spongy graphene,
      which form an irregular 3D porous structure that displays pores with an average
      size of 15-20 nm. Several characterization techniques have confirmed the porous
      nature of the collected layers. The analyses of the aqueous solution confirmed
      the presence of GQDs with dimensions of about 2-5 nm. It is found that the
      formation of both PG and GQDs depends on the fs-laser ablation energy. At laser
      fluences less than 12 J cm(-2), no evidence of either PG or GQDs is detected.
      However, polyynes with six and eight carbon atoms per chain are found in the
      solution. For laser energies in the 20-30 J cm(-2) range, these polyynes
      disappeared, while PG and GQDs were found at the water-air interface and in the
      solution, respectively. The origin of these materials can be explained based on
      the mechanisms for water breakdown and coal gasification. The absence of PG and
      GQDs, after the laser ablation of HOPG in liquid nitrogen, confirms the proposed
      mechanisms. 

PMID- 24435550
TI  - Influence of inductive effects and steric encumbrance on the catecholase
      activities of copper(II) complexes of reduced Schiff base ligands.
AB  - A series of copper(ii) complexes derived from reduced Schiff base ligands has
      been synthesized and characterized by single-crystal X-ray diffraction and
      spectroscopic analyses. With the exception of [Cu(Ala5NO2)(H2O)] (), which
      crystallized as a mononuclear repeating unit, [Cu2L2(H2O)x(DMSO)y].solvent (L =
      Ala5H (), Ala5OMe (), Ala5Cl (), Ala5Br (), Gly5Br (), Val5Br () and Leu5Br (), x
      = 1 or 2, y = 0 or 1, solvent = MeOH or DMSO and H2O) crystallized as phenoxo
      bridged dinuclear building units containing Cu2O2 cores. In , , , and , the axial
      positions are occupied by solvent ligands and carboxylate oxygen atoms from
      adjacent dimers, resulting in the formation of 1D helical coordination polymers.
      In , a 2D network is constructed by utilizing weak CuO interactions (~2.7 A) with
      carboxylate groups. All complexes have been investigated for their catecholase
      activities with 3,5-DTBC, and they show significant catalytic activities except
      for . The catalytic activities are also observed to increase with increasing +I
      effects, as well as increase with increasing steric bulkiness on the alpha-carbon
      of the carboxylate group. 

PMID- 24435551
TI  - Social aversive stimuli presented to the mother produce the precocious expression
      of fear in rat pups.
AB  - During the stress hypo-responsive period, rat pups do not display fear responses
      toward adult males, yet they exhibit distress behavior in isolation. Since the
      mother modulates her offspring's affective development, we hypothesized that by
      altering the mother's behavior, a prolonged stressful situation would modify the
      ontogeny of the fear responses and distress behaviors in pups. Therefore, we
      repeatedly exposed the mother-litter dyad to different socially stressful stimuli
      and subsequently evaluated in 8-day-old pups their fear responses toward an
      anesthetized male, as well as their distress behavior in isolation. Our results
      show that repeated exposure to unfamiliar males and females, which altered
      maternal behavior by eliciting aggression in the mother, was associated with the
      precocious fear responses in pups, though without altering their distress
      behavior in isolation. We propose that the mother, as the principal mediator of
      environmental influences, provokes the precocious expression of fear in pups
      through alterations in her maternal behavior.

PMID- 24435552
TI  - Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on
      primary nephrotic syndrome.
AB  - The aim of the present study was to investigate whether the four guanosines
      (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen
      activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic
      syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with
      40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by
      polymerase chain reaction and DNA sequencing. Associations between the PAI-1
      4G/5G polymorphism and clinical features and pathological types of PNS were
      analyzed. The results indicated that the PAI-1 genotype distribution is
      significantly different between patients with PNS and healthy controls, with
      significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G
      genotype detected in PNS patients compared to controls (both P<0.05). The
      frequency of the 4G allele was also significantly higher in PNS patients compared
      to healthy controls (P<0.01). Among the different pathological types of PNS, IgA
      nephropathy (IgAN) and membranous nephropathy (MN) were associated with
      significantly increased frequencies of the 4G/4G and 4G/5G genotypes, as well as
      of the 4G allele. The increased 4G frequency was also detected in patients with
      minimal change disease (MCD). Significantly increased international normalized
      ratio (INR) and prolonged activated partial thromboplastin time (APTT) were
      observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was
      not significantly different among the three genotypes. In conclusion, the 4G
      allele of the PAI-1 gene appears to be associated with PNS, especially in MN and
      IgAN patients. These findings suggest that specific targeting may be required for
      the treatment of PNS patients with the 4G/4G genotype.

PMID- 24435553
TI  - A cascading reaction sequence involving ligand-directed azaelectrocyclization and
      autooxidation-induced fluorescence recovery enables visualization of target
      proteins on the surfaces of live cells.
AB  - A general probe designed to induce a cascading sequence of reactions on a target
      protein was efficiently synthesized. The cascading reaction sequence involved (i)
      ligand-directed azaelectrocyclization with lysine and (ii) the autooxidation
      induced release of a fluorescence quencher from the labeled protein. The probe
      was linked to a cyclic RGDyK peptide to enable the selective visualization of
      integrin alphaVbeta3 on the surfaces of live cells. 

PMID- 24435556
TI  - [Somatic Conversion (Paramutation) at the sulfurea Locus of Lycopersicon
      esculentum Mill. : IV. The Genotypic Determination of the Frequency of
      Conversion].
AB  - 1. Several lines of Lycopersicon esculentum, which are heterozygous for a mutant
      sulfurea (sulf) allele vary greatly in the percentage of variegated plants among
      the heterozygotes. This variegation is caused by somatic conversion
      (paramutation). The different frequency of conversion is due to the presence of
      different sulf alleles. Within the sulfurea (pura) (sulf (pura) ) and sulfurea
      (variegata) (sulf (vag) ) groups there are different alleles, which - though
      indistinguishable in homozygous condition - can be distinguished by their
      different conversion activity (paramutagenicity) in heterozygotes with sulf (+).
      2. The conversion activity (paramutagenicity) of an allele is expressed by the
      percentage of green-yellow variegated plants among the heterozygotes (e. g. sulf
      (pura-90%) means: 90 plants out of 100, which are heterozygous for this
      particular sulf (pura) allele, are variegated, and 10 are entirely green). 3. The
      conversion activity (paramutagenicity) of a particular sulf allele can be changed
      by mutations; it can be either increased or decreased. 4. Crosses have been made
      between sulf homozygotes (Lycopersicon esculentum, variety Lukullus) and
      different taxa of the subgenus Eulycopersicon (L. esculentum: marker stocks,
      German tomato varieties, distantly related varieties from South and Central
      America; L. pimpinellifolium). Within the subgenus Eulycopersicon the frequency
      of somatic conversion (paramutation) is - within the range of random and
      modificative fluctuations - determined only by the conversion activity
      (paramutagenicity) of the special sulf allele present. Effects of the genetic
      background could not be demonstrated. Conversion-stable (non-paramutable) sulf
      (+) isoalleles have not been found in this subgenus. 5. The sulf (pura) group
      consists of alleles with all possible degrees of conversion activity
      (paramutagenicity) between 0% and 100% for particular years and average
      conversion values between 3,6% and 92,9% for several years. The sulf (vag)
      alleles have a lower conversion activity; its maximum is about 12%. No sulf
      alleles have been found which have entirely lost their conversion activity. 6.
      After crossing sulf heterozygotes (L. esculentum) with the distantly related
      species Lycopersicon hirsutum (subgenus Eriopersicon) and Solanum pennellii
      significant deviations from the expected 3?1 segregation for sulf have been found
      in F 1 and F 3; there is a distinct deficit of sulf sulf seedlings. In F 1
      species hybrids somatic conversion (paramutation) occurred very seldom (less than
      2%). However in F 2 of both crosses some progenies had frequencies of conversion
      up to 9,3% (L. esc. x L. hirs.) and 8,5% (L. esc. x Sol. pen.). In F 3 some
      progenies had frequencies which were slightly higher than those in F 2. In F 4 a
      progeny has had a frequency of conversion of 61,7%. 7. In F 1, F 2, F 3and F 4 of
      these species hybrids the sulf (+) allele is from L. hirsutum or S. pennellii and
      the sulf allele is from L. esculentum; i.e. the system sulf (+) - sulf is always
      the same. Therefore the differences in the conversion frequency between F 1 and F
      2, F 3and F 4 respectively indicate an influence of the genetic background. The
      genetic background of the subgenus Eulycopersicon allows the full expression of
      the conversion system sulf (+) - sulf. Genes of L. hirsutum or S. pennellii,
      however, intensely inhibit the occurrence of somatic conversion in F 1. Genetic
      recombination in the species hybrids leads to the occurrence of genotypes in F 2,
      F 3and F 4 which allow conversion to take place more frequently. 8. In the
      discussion the results obtained with the sulf system of the tomato are compared
      with those of the analysis of the paramutation systems at the R and B locus in
      Zea mays, at the cruciata locus in Oenothera and in the rogue heterozygotes of
      Pisum sativum. 

PMID- 24435555
TI  - Coeliac disease: an old or a new disease? History of a pathology.
AB  - The celiac disease is an ancient pathology, present since the introduction of the
      wheat in the diet, of which the first description of the compatible clinical
      symptoms and signs goes back to 250 A.D. Today it is known that the expression of
      this pathology is multifaceted, ranging from clinical features indicative of
      bowel disease and malabsorption, until symptoms once unexpected, because of their
      extra-digestive clinical features. With our work, we wanted to retrace the
      history of this disease, correlating it with the intake of gluten present in
      wheat after cooking , ever since mankind has increased the cultivation of
      cereals. Re-evaluating the clinical and instrumental methods for the diagnosis of
      Celiac Disease, and benefitting from the most modern techniques for the
      morphological, biochemical and genetic study of the patients, we sought to
      understand whether the incidence of the disease is actually increased or if has
      been considered less frequent for the lower valuation of the signs once deemed
      more atypical, but currently considered preliminary indicative of the pathology,
      for its association with other autoimmune diseases, and for the study of some
      genetic and familiar characteristics. Each of these factors has led the modern
      medicine to increase epidemiological studies and expand the research potential
      carriers of celiac disease with safer diagnostic tests. 

PMID- 24435554
TI  - Galpha12 structural determinants of Hsp90 interaction are necessary for serum
      response element-mediated transcriptional activation.
AB  - The G12/13 class of heterotrimeric G proteins, comprising the alpha-subunits
      Galpha12 and Galpha13, regulates multiple aspects of cellular behavior, including
      proliferation and cytoskeletal rearrangements. Although guanine nucleotide
      exchange factors for the monomeric G protein Rho (RhoGEFs) are well characterized
      as effectors of this G protein class, a variety of other downstream targets has
      been reported. To identify Galpha12 determinants that mediate specific protein
      interactions, we used a structural and evolutionary comparison between the
      G12/13, Gs, Gi, and Gq classes to identify "class-distinctive" residues in
      Galpha12 and Galpha13. Mutation of these residues in Galpha12 to their deduced
      ancestral forms revealed a subset necessary for activation of serum response
      element (SRE)-mediated transcription, a G12/13-stimulated pathway implicated in
      cell proliferative signaling. Unexpectedly, this subset of Galpha12 mutants
      showed impaired binding to heat-shock protein 90 (Hsp90) while retaining binding
      to RhoGEFs. Corresponding mutants of Galpha13 exhibited robust SRE activation,
      suggesting a Galpha12-specific mechanism, and inhibition of Hsp90 by geldanamycin
      or small interfering RNA-mediated lowering of Hsp90 levels resulted in greater
      downregulation of Galpha12 than Galpha13 signaling in SRE activation experiments.
      Furthermore, the Drosophila G12/13 homolog Concertina was unable to signal to SRE
      in mammalian cells, and Galpha12:Concertina chimeras revealed Galpha12-specific
      determinants of SRE activation within the switch regions and a C-terminal region.
      These findings identify Galpha12 determinants of SRE activation, implicate
      Galpha12:Hsp90 interaction in this signaling mechanism, and illuminate structural
      features that arose during evolution of Galpha12 and Galpha13 to allow bifurcated
      mechanisms of signaling to a common cell proliferative pathway.

PMID- 24435557
TI  - Rate, composition and efficiency of growth in mice selected for large and small
      body weight.
AB  - Mice selected for high (H6) and low (L6) 6-week body weight and a randombred
      control population (C1) were characterized for rate, composition and efficiency
      of growth. Individual body weights were obtained from birth to 8 weeks of age on
      682 mice representative of the three lines. Individual whole carcass
      determinations of water, fat, ash and protein (residual) were obtained for 180
      mice sampled weekly from 3-8 weeks of age. Efficiency of feed utilization was
      estimated from individual body weight and feed consumption data obtained on 189
      mice from 3-8 weeks of age. Growth curves for body weight and gain in body
      weight, constructed by line and sex, showed a temporary retardation of maximum
      growth rate in the L6 line, which was attributed in part to an extended
      depression in growth following weaning. The composition of growth yielded no
      evidence that the more rapid growth rate in the H6 line resulted from an increase
      in fat deposition relative to the other carcass components. A decrease in fat
      percent at 7 weeks of age in the H6 and C1 lines was not evident in the L6 line
      until 8 weeks of age. Females had a higher percentage carcass fat than did males
      during the 4-7 weeks growth period, but this difference was essentially reduced
      to zero by 8 weeks of age. Percentage water was highly correlated negatively with
      percentage fat. Percentages protein and ash were essentially constant across
      lines and ages. A positive relation between rate and efficiency of growth was
      observed between lines. Consistent sex differences, males more efficient than
      females, were observed prior to 6 weeks of age, but were not evident in the later
      (6-8 week) data. 

PMID- 24435558
TI  - Desynapsis and the blockage of meiosis in Pennisetum orientale Rich.
AB  - Meiotic behaviour of a desynaptic plant of Pennisetum orientale Rich., which
      seems to have arisen through spontaneous gene mutation/s, is recorded. The plant
      showed an extremely rare type of desynapsis in which the precocious falling-apart
      of the homologous chromosomes was accompanied by the blockage of the meiotic
      course from metaphase I onwards. Different factors which may have led to the
      failure of chromosome synapsis and to the blockage of the meiotic division are
      discussed. The possibility of the participation of different enzymes in the
      initiation and continued progress of chromosome synapsis as well as for the
      different meiotic steps is considered. It has been inferred that the absence or
      later inactivation of these genetically-controlled enzymes might have resulted in
      the meiotic abnormalities observed in the present material. Another plausible
      regulatory mechanism based on the existence of a switch - through gene-repressing
      effect of histones - has been hypothesized and its possible evolutionary
      significance indicated. 

PMID- 24435559
TI  - [Certation experiment concerning competition between pollentubes under the
      influence of the locus Ga in Oenothera].
AB  - The material for the experiments were two Oenothera-Hybrids with the complexes
      (h) hookeri and flavens which were heterozygous for the gametophytic gene ga and
      for the genes s and de. Certation experiments were done by pollinating the styles
      of Oe. hookeri sulfurea with different amounts of pollen grains and by
      interruption of pollen tube growth by cutting off the styles at different times
      after pollination.There is no correlation between the experimental treatment and
      the segregation for the two genes in the progeny. The competition between pollen
      cells with the alleles respectively ga (+) and ga (-) therefore cannot be due to
      differences in growth rates during the developmental stage of pollen tube-growth
      in the style but must occur during the germination of the pollen on the stigma or
      in the last stage of development of the pollen tubes shortly before
      fertilization. The data reveal great variability of crossing-over in the
      chromosome-region under investigation. 

PMID- 24435560
TI  - Mutant gene frequencies in cats of Southern England.
AB  - Three areas in Southern England have been sampled for frequency of nine mutant
      genes among the domestic cat population. The significance of the derived
      estimates are discussed and a brief comparison is made with the earlier estimate
      obtained by SEARLE. The frequencies seem comparable in the two surveys except for
      genes O and d. The estimates of these from the present study are significantly
      higher than those found earlier. Tentatively, it is proposed that human
      preference for orange cats may be responsible for the increase in O. No obvious
      reason exists for the higher frequency of d. 

PMID- 24435561
TI  - Formaldehyde-induced mutations in Drosophila melanogaster in dependence of the
      presence of acids.
AB  - The mutagenic activity of various combinations of formaldehyde, formic acid,
      acetic acid and hydrochloric acid was investigated by a sex-linked lethal test.
      All combinations were mutagenic and showed a mutation pattern from which it is
      concluded that in feeding experiments spermatocytes I are especially sensitive to
      the pairs of chemicals tested. In vapour experiments all germ cell stages were
      found to be susceptible.The presence of volatile acids was found to be necessary
      for the mutagenic activity of formaldehyde in the vapour state. Mutagenic effects
      were also observed in larvel feeding experiments, in which only these acids were
      added to the medium. Experiments with stabilized pH at 7.5 did not show a
      significant mutagenic effect of formaldehyde.It is postulated that the tested
      agents are catalase inhibitors, which promote the formation of peroxides or free
      radicals which interfere with DNA replication, thus producing mutations. 

PMID- 24435562
TI  - REST enabling the report template library.
AB  - Structured reporting, created when a standardized template with organized
      subheadings is combined with relevant observations of a diagnostic study into a
      meaningful result, has the potential to raise both the quality and the
      predictability of the radiologist report, revolutionizing the workflow and its
      outcomes. These templates contain great value, as they carve a path based on best
      practice for the radiologist to follow, and thus should be shared, reviewed, and
      improved. Unfortunately, these templates are often not shareable today due to a
      lack of standards for describing and transporting templates. This paper outlines
      and discusses an appropriate and effective electronic method for transporting
      radiology report templates using of the style of representational state transfer
      (REST). Enabling a structured radiology report template library with REST enables
      just-in-time accessibility of templates, achieving efficiencies and
      effectiveness. 

PMID- 24435563
TI  - Large splittings of the 4f shell of Ce3+ in garnets.
AB  - Ab initio embedded cluster calculations on Ce(3+)-doped Y3Al5O12, Lu3Al5O12,
      Gd3Al5O12, Y3Ga5O12, Lu3Ga5O12, and Gd3Ga5O12, which do not make use of any
      adjustable parameter, support recent assignments of the seventh 4f level of
      Ce(3+) in garnets [Przybylinska et al., Appl. Phys. Lett., 2013, 102, 241112] and
      that the splitting of the 4f shell of Ce(3+) in these materials is slightly
      smaller than 4000 cm(-1) and much larger than the 2000-2500 cm(-1) commonly
      assumed in analyses of 5d -> 4f emission bands. Why this wrong assumption has
      been working well so far is explained by the fact that the intensity of the
      emission to the seventh level of the 4f(1) configuration is found to be only one
      hundredth of the integrated intensity of the emissions to the other six levels,
      which group themselves into two sets of three individual levels separated by 2000
      2500 cm(-1). The effective field splitting and the spin-orbit coupling splitting
      are found to be of the same size. From a strong field coupling point of view, the
      first six levels result from the interactions between (2)T(2u) and (2)T(1u) cubic
      levels and the higher, isolated seventh level comes directly from the cubic
      (2)A(2u). From a weak field coupling point of view, the first three levels result
      from the splitting of (2)F(5/2), the second three levels from the splitting of
      (2)F(7/2) and the seventh level from a strong, cubic field driven interaction
      between (2)F(7/2) and (2)F(5/2) components [Herrmann et al., J. Appl. Phys.,
      1966, 37, 1312].

PMID- 24435567
TI  - The end of an era.

PMID- 24435565
TI  - Time-resolved multidimensional NMR with non-uniform sampling.
AB  - Time-resolved experiments demand high resolution both in spectral dimensions and
      in time of the studied kinetic process. The latter requirement traditionally
      prohibits applications of the multidimensional experiments, which, although
      capable of providing invaluable information about structure and dynamics and
      almost unlimited spectral resolution, require too lengthy data collection. Our
      work shows that the problem has a solution in using modern methods of NMR data
      collection and signal processing. A continuous fast pulsing three-dimensional
      experiment is acquired using non-uniform sampling during full time of the studied
      reaction. High sensitivity and time-resolution of a few minutes is achieved by
      simultaneous processing of the full data set with the multi-dimensional
      decomposition. The method is verified and illustrated in realistic simulations
      and by measuring deuterium exchange rates of amide protons in ubiquitin. We
      applied the method for characterizing kinetics of in vitro phosphorylation of two
      tyrosine residues in an intrinsically disordered cytosolic domain of the B cell
      receptor protein CD79b. Signals of many residues including tyrosines in both
      phosphorylated and unmodified forms of CD79b are found in a heavily crowded
      region of 2D 1H-15N correlation spectrum and the significantly enhanced spectral
      resolution provided by the 3D time-resolved approach was essential for the
      quantitative site-specific analysis.

PMID- 24435566
TI  - Solution structure of the RecQ C-terminal domain of human Bloom syndrome protein.
AB  - RecQ C-terminal (RQC) domain is known as the main DNA binding module of RecQ
      helicases such as Bloom syndrome protein (BLM) and Werner syndrome protein (WRN)
      that recognizes various DNA structures. Even though BLM is able to resolve
      various DNA structures similarly to WRN, BLM has different binding preferences
      for DNA substrates from WRN. In this study, we determined the solution structure
      of the RQC domain of human BLM. The structure shares the common winged-helix
      motif with other RQC domains. However, half of the N-terminal has unstructured
      regions (alpha1-alpha2 loop and alpha3 region), and the aromatic side chain on
      the top of the beta-hairpin, which is important for DNA duplex strand separation
      in other RQC domains, is substituted with a negatively charged residue (D1165)
      followed by the polar residue (Q1166). The structurally distinctive features of
      the RQC domain of human BLM suggest that the DNA binding modes of the BLM RQC
      domain may be different from those of other RQC domains. 

PMID- 24435568
TI  - Graduate medical education financing in psychiatry.
AB  - Psychiatry residency training programs are being affected by changes in graduate
      medical education financing. Program budgets are increasingly being constricted.
      Training directors will need to be better informed about how programs are
      financed if they are to function effectively and to advocate successfully f or
      training funds. The authors illustrate the present mechanisms of graduate medical
      education financing with examples. The possible effect of the coming reform in
      health care financing on psychiatry residency training is examined. 

PMID- 24435569
TI  - An observation and group dynamics model for teaching psychoanalytic
      psychotherapy.
AB  - Teaching and learning psychoanalytic psychotherapy are complex tasks involving
      the necessary integration of cognitive and affective elements. A model for this
      process is described that uses long-term observation of the teacher-mentor
      conducting therapy with a single patient. This method supplements and complements
      the use of supervision and case conferences to train psychoanalytic
      psychotherapists. The advantages of the observational mode are considered as well
      as the dynamics inherent in the group process and the discussion that follows the
      observation period. Such a pedagogical method emphasizes the important
      integration of affective and cognitive elements. 

PMID- 24435570
TI  - Providing residents with a comprehensive educational program in outpatient
      psychiatry : integrating an outpatient curriculum into outpatient management
      teams.
AB  - As part of their efforts to prepare psychiatry residents for comprehensive,
      practical outpatient psychiatric practice, the authors have established an
      organized training program in ambulatory psychiatry. The program consists of
      outpatient management teams that run from mid-PGY-2 to PGY-4, a specified minimum
      number of mandatory outpatient hours for continuity patient care, and suggested
      guidelines for residents' outpatient experiences. An outpatient management team
      curriculum has been designed for team leaders and trainees that consists of
      specific topics in outpatient care, associated learning objectives, and readings
      for each topic. This curriculum, which supplements our previous program of
      conferences, individual supervision, and a yearlong psychotherapy seminar series,
      has been refined over the past 5 years. The authors describe the program and the
      topics included in the curriculum. 

PMID- 24435571
TI  - Stress and adaptation in learning and practicing medicine : an elective course
      for medical students.
AB  - In their pursuit of careers in medicine, medical trainees and practicing
      physicians frequently endure significant levels of biopsychosocial distress.
      Psychiatry can play an important role in providing education about successful
      adaptation to a medical career and how to avoid dysfunctional states. The author
      describes a course designed to provide instruction to help medical students
      improve their adaptive skills. The course emphasizes preventive methods for
      maintaining well-being throughout a medical career. Both didactic and
      experiential methods of instruction are used to teach the class. The course
      targets a number of topics considered important for adaptation and well-being,
      using small group discussion to help students explore their ideas and
      experiences. By use of a concept referred to as the "longitudinal analogous
      experience," current experience is explored to provide insights that hopefully
      will lead to more effective adaptation in the future. The instruction encourages
      the medical student to develop and use adaptive coping styles and skills to
      maintain an effective level of overall functioning throughout the training and
      practice years. 

PMID- 24435572
TI  - Psychiatry department retreats: uses and benefit.

PMID- 24435573
TI  - Frequently asked questions about an added qualification certificate in
      consultation-liaison psychiatry.

PMID- 24435575
TI  - Not all sharks are "swimming noses": variation in olfactory bulb size in
      cartilaginous fishes.
AB  - Olfaction is a universal modality by which all animals sample chemical stimuli
      from their environment. In cartilaginous fishes, olfaction is critical for
      various survival tasks including localizing prey, avoiding predators, and
      chemosensory communication with conspecifics. Little is known, however, about
      interspecific variation in olfactory capability in these fishes, or whether the
      relative importance of olfaction in relation to other sensory systems varies with
      regard to ecological factors, such as habitat and lifestyle. In this study, we
      have addressed these questions by directly examining interspecific variation in
      the size of the olfactory bulbs (OB), the region of the brain that receives the
      primary sensory projections from the olfactory nerve, in 58 species of
      cartilaginous fishes. Relative OB size was compared among species occupying
      different ecological niches. Our results show that the OBs maintain a substantial
      level of allometric independence from the rest of the brain across cartilaginous
      fishes and that OB size is highly variable among species. These findings are
      supported by phylogenetic generalized least-squares models, which show that this
      variability is correlated with ecological niche, particularly habitat. The
      relatively largest OBs were found in pelagic-coastal/oceanic sharks, especially
      migratory species such as Carcharodon carcharias and Galeocerdo cuvier. Deep-sea
      species also possess large OBs, suggesting a greater reliance on olfaction in
      habitats where vision may be compromised. In contrast, the smallest OBs were
      found in the majority of reef-associated species, including sharks from the
      families Carcharhinidae and Hemiscyllidae and dasyatid batoids. These results
      suggest that there is great variability in the degree to which these fishes rely
      on olfactory cues. The OBs have been widely used as a neuroanatomical proxy for
      olfactory capability in vertebrates, and we speculate that differences in
      olfactory capabilities may be the result of functional rather than phylogenetic
      adaptations. 

PMID- 24435576
TI  - The effect of different night conditions on the CO2 fixation in a lichen
      Xanthoria parietina.
AB  - CO2 fixation was studied in a lichen, Xanthoria parietina, kept in continuous
      light, and with cyclic changes in light intensity, dark period or temperature.
      The diurnal and seasonal courses of CO2 exchange were followed. The rate of net
      photosynthesis was observed to fall from morning to evening, and this decline was
      more pronounced in winter than in summer. The maximal net photosynthetic rate,
      223 ng CO2g(-1)dws(-1), occured in winter and the minimum, 94 ng CO2g(-1)dws(-1),
      late in spring. The light compensation point in summer was four times as high as
      in winter. In continuous light (180 or 90 MUmol photons m(-2)s(-1), 15 degrees C)
      net photosynthesis decreased noticeably during one week, falling below the level
      maintained in a 12 h light: 12 h dark cycle. Photosynthetic activity did not
      decrease, however, in lichens held in continuous light (90 MUmol photons m(-2)s(
      1)) with cyclic changes of temperature (12 h 20  degrees C: 12 h 5  degrees C).
      Active photosynthesis was also maintained in light of cyclically changing
      intensity (12 h: 12 h, 15  degrees C) when night-time light was at least 75%
      lower than illumination by day. A dark period of 4 hours in a 24-h light:dark
      cycle was sufficient to keep CO2 fixation at the control level. It seems that
      plants need an unproductive period during the day to survive and this can be
      induced by fluctuations in light and/or temperature. 

PMID- 24435577
TI  - Determination of the total chlorophyll distribution pattern in living leaves.
AB  - Tradescantia albiflora-leaves were used in developing a determination method for
      chlorophyll in living leaves using a microscopic spectro photometer (MPV,
      Leitz).The wavelength of the maximal absorption for chlorophyll a was found to be
      at 670 nm and for chlorophyll b at 652 nm. To calculate the reference values the
      intensity of the transmitted light at 750 nm was measured. The absorption at 750
      nm results only from the chlorophyll free structure in the leaves. To correct
      optical errors the two-wavelength method was used. The values gained in arbitrary
      units were calibrated against data measured in the conventional way. The
      resulting calibration line shows a very high correlation coefficient where
      r(2)=0.997. It was proved that the calibration line was also correct for
      determinations with leaves from other plant species.Using this determination
      method the chlorophyll content of small areas on the living leaf blade of
      Phaseolus vulgaris was determined.As consequence of the thicker mesophyll
      accompanying the veins the chlorophyll concentration is 30% higher in this
      tissue. A lower chlorophyll concentration was observed in the thinner leaf tip
      and in the oldest regions at the leaf ground.At the leaf tip, the leaf ground and
      in the tissue along the veins an iron deficit causes less bleaching than in the
      areoles. In the same leaf regions the bleaching herbicide atrazine induces rapid
      bleaching if supplied through transpiration stream. The application of Atrazine
      on the leaf surface gives rise to the contrary effect.All these phenomena seem to
      be a result of a differing water supply by the xylem vessels. 

PMID- 24435578
TI  - Effect of dissolved inorganic carbon on oxygen evolution and uptake by
      Chlamydomonas reinhardtii suspensions adapted to ambient and CO2-enriched air.
AB  - Mass spectrometric measurements of (16)O2 and (18)O2 isotopes were used to
      compare the rates of gross O2 evolution (E0), O2 uptake (U0) and net O2 evolution
      (NET) in relation to different concentrations of dissolved inorganic carbon (DIC)
      by Chlamydomonas reinhardtii cells grown in air (air-grown), in air enriched with
      5% CO2 (CO2-grown) and by cells grown in 5% CO2 and then adapted to air for 6h
      (air-adapted).At a photon fluence rate (PFR) saturating for photosynthesis (700
      MUmol photons m(-2) s(-1)), pH=7.0 and 28 degrees C, U0 equalled E0 at the DIC
      compensation point which was 10MUM DIC for CO2-grown and zero for air-grown
      cells. Both E0 and U0 were strongly dependent on DIC and reached DIC saturation
      at 480 MUM and 70 MUM for CO2-grown and air-grown algae respectively. U0
      increased from DIC compensation to DIC saturation. The U0 values were about 40
      (CO2-grown), 165 (air-adapted) and 60 MUmol O2 mg Chl(-1) h(-1) (air-grown).
      Above DIC compensation the U0/E0 ratios of air-adapted and air-grown algae were
      always higher than those of CO2-grown cells. These differences in O2 exchange
      between CO2- and air-grown algae seem to be inducable since air-adapted algae
      respond similarly to air-grown cells.For all algae, the rates of dark respiratory
      O2 uptake measured 5 min after darkening were considerably lower than the rates
      of O2 uptake just before darkening. The contribution of dark respiration,
      photorespiration and the Mehler reaction to U0 is discussed and the energy
      requirement of the inducable CO2/HCO3 (-) concentrating mechanism present in air
      adapted and air-grown C. reinhardtii cells is considered. 

PMID- 24435579
TI  - Photoinhibition of photosynthesis: effect of O2 and selective excitation of the
      photosystems in intact Lemna gibba plants.
AB  - Intact Lemna gibba plants were photoinhibited under anaerobic conditions on
      illumination with monochromatic light which selectively excited the photosystems.
      Photoinhibition was less when PS 1 was excited and greatest when mainly PS 2 was
      excited, which suggests that PS 2 was most damaged by photoinhibition induced in
      complete absence of O2 and CO2.The illumination of plants with monochromatic
      light exciting PS 1, at different O2 concentrations (in CO2 deficient
      conditions), showed that PS 1 photoinhibition was increased at the low O2
      concentrations. The damage to PS 1 was more evident at 2% O2 than at the higher
      O2 concentrations.CO2 as well as O2 at atmospheric concentration, (air), was
      necessary for complete protection of the plant from photoinhibition when both
      photosystems were excited either separately or together. 

PMID- 24435580
TI  - Proton decay kinetics for vesicles containing buffers-an analytical solution.
AB  - The problem of predicting the kinetics of proton efflux and the decay of the
      internal proton concentration for vesicles containing one or more buffers for
      which the internal proton concentration is initially higher than that of the
      surrounding medium is examined. An analytical solution is derived that describes
      the time course of the proton efflux from vesicles and the decay of the internal
      proton concentration under conditions of zero transmembrane electric potential.
      The effect of the internal buffers is to increase the time required for the
      proton concentration gradient to equilibrate across the membrane. To simplify the
      analysis we assume that the equilibration of the internal and external proton
      activity is due primarily to proton diffusion through the membrane, and not to
      hydroxyl ion flux. For a vesicle containing a single buffer the solution requires
      six independent physical parameters: the initial internal proton concentration,
      the external proton concentration, the ratio of the vesicle surface area to the
      internal volume, the permeability coefficient of the membrane for protons, the
      total concentration of the internal buffer, and the equilibrium constant for the
      dissociation of the internal buffer. Determination of these physical values is
      sufficient to predict the time dependence of the internal proton concentration
      and of the proton efflux. Over a pH range that is below or near the pK of the
      internal buffer the solution is complex. However, if the initial pH is one unit
      or more higher than the pK of the internal buffer the kinetics of the internal
      proton concentration and proton efflux can be described by a pseudo first order
      reaction. In this case the apparent rate constant depends linearly on the
      permeability coefficient and is dominated by the total internal buffer
      concentration and its pK. For example, increasing the internal buffer
      concentration inside a vesicle by 10-fold results in an approximately 10-fold
      increase in the half-time of the proton efflux kinetics. The theoretical analysis
      is applied to thylakiod vesicles using experimentally determined values for the
      physical parameters. The predictions of the analysis are compared to
      experimentally observed kinetics. 

PMID- 24435581
TI  - Inhibition of the photosynthetic electron transport of isolated thylakoids by
      hemolyzed rabbit sera. Evidence for the potential involvement of parallel
      electron transport in photosystem I Mehler reactions.
AB  - The inhibition patterns of rabbit sera (RS1 & RS2) from two different rabbits on
      the photosynthetic electron transport of isolated spinach thylakoids were
      studied. Fifty MUl of RSI were required for 100% inhibition of a H2O -> MV/O2
      reaction, while only 10 MUl of a 1:10 dilution of RS2 were needed for 100%
      inhibition. The RS2 serum was greatly hemolyzed. The gamma-globulin fraction from
      purified rabbit serum (RS1) did not inhibit photosynthetic electron transport,
      indicating that the antibody fraction of the rabbit serum does not contain the
      inhibitor. It appears that the inhibitor is from the hemolyzed red blood cells.
      Rabbit sera added prior to chloroplast illumination caused no inhibition, while
      addition of rabbit sera during illumination inhibited a H2O -> MV/O2 reaction
      within 1-3s. Aminotriazole, a catalase inhibitor, did not affect the efficacy of
      the rabbit sera indicating that the unknown rabbit serum inhibitor is not
      catalase. Various Hill reactions were employed to determine the site of
      inhibition. Rabbit sera inhibited the following reactions: DHQ/DCMU -> MV/O2,
      DAD/Asc/DBMIB -> MV/O2, and DCIP/Asc/DBMIB -> MV/O2. Rabbit sera did not inhibit
      a H2O -> DADox reaction indicating that inhibition is on the reducing side of
      PSI. However, a H2O -> Fd/NADP(+) reaction was not inhibited by rabbit sera. NADP
      did not interfere with the ability of RS2 to inhibit a MV-mediated Mehler
      reaction. In simultaneously measured assays of Fd-mediated O2 and NADP(+)
      reductions, RS2 serum inhibited the reduction of O2 by ferredoxin without
      inhibiting the reduction of NADP(+). These results indicate the potential
      involvement of parallel (branched) electron transport of the reducing side of PSI
      in the reduction of oxygen. 

PMID- 24435582
TI  - Characterization of a light-dependent glutamate synthase activity in
      Chlamydomonas reinhardtii.
AB  - Photosynthetically active vesicles prepared from Chlamydomonas reinhardtii
      retained a light-dependent glutamate synthase activity which was highly specific
      for 2-oxoglutarate (Km=2.1 mM) and L-glutamine (Km=0.9 mM) as amido group
      acceptor and donor respectively. This activity was inhibited by azaserine, p
      hydroxymercuribenzoate and 3-(p-chlorophenyl)-1,1-dimethyl urea.Light-dependent
      synthesis of glutamate was also obtained by coupling Chlamydomonas photosynthetic
      particles to purified ferredoxin-glutamate synthase, using ascorbate and 2,6
      dichlorophenol-indophenol as electron donor. This system was also specific for 2
      oxoglutarate (Km=1 mM) and L-glutamine (Km=0.8 mM) as substrates, and was
      stimulated by dithioerythritol. Azaserine and p-hydroxymercuribenzoate, but not 3
      (p-chlorophenyl)-1,1-dimethyl urea, inhibited the reconstituted activity; high
      concentrations of 2-oxoglutarate were inhibitory. 

PMID- 24435583
TI  - Fluorescence polarization of trypsin digested photosystem II membranes.
AB  - Fluorescence polarization of photosystem II particles treated with trypsin and
      incubated with high salt-medium (2M NaCl) was investigated. The presence of
      atrazine and TMPD in normal and salt-washed particles induced a decrease in the
      polarization ratios. Similar results were obtained at low concentrations of
      trypsin. On the basis of our observations we suggest that the presence of these
      perturbing agents causes a reorganisation of the membrane components and alters
      pigment-pigment and pigment-protein interactions. The results of fluorescence
      polarization demonstrate trypsin entry into the membrane after the digestion of
      the peripheral proteins. 

PMID- 24435585
TI  - Effect of intervention in the diacylglycerol-protein kinase C signaling pathway
      on JNK1 expression and its downstream signaling in diabetic cardiomyopathy.
AB  - This study aimed to investigate the expression of signaling molecules, such as c
      Jun N-terminal kinase 1 (JNK1) and insulin receptor substrate 1 (IRS1), in the
      myocardium of diabetic rats following intervention in the diacylglycerol-protein
      kinase C (DAG-PKC) signal transduction pathway. The rats were divided into three
      groups, the diabetic model, control and breviscapine-treated diabetes
      (intervention) group. Following modeling and drug treatment, hematoxylin and
      eosin (HE) and Masson staining and electron microscopy were used to observe the
      pathological changes in the rat myocardium. The expression of PKC-beta2, JNK1,
      and IRS1 was assessed in rat myocardium by immunohistochemistry and quantitative
      polymerase chain reaction (qPCR). The expression levels of PKC-beta2, JNK1,
      phosphorylated JNK (p-JNK) and IRS1 in the diabetic model group were
      significantly higher than those in the control group. Furthermore, compared with
      the diabetic model group, expression levels of PKC-beta2, JNK1, p-JNK and IRS1
      were significantly reduced following intervention in the DAG-PKC signal
      transduction pathway. The DAG-PKC pathway may affect downstream signaling through
      JNK1 (the common signal point of the G-protein receptor pathway and insulin
      receptor pathway at the cell membrane) to result in the occurrence and
      development of diabetic cardiomyopathy (DCM). The series of signal points DAG-PKC
      JNK1-IRS1-Akt/PKB-mTOR-p70S6K1 is a potential pathway for inducing DCM by DAG-PKC
      signal transduction. Enhanced expression of JNK1, p-JNK and IRS1 may accelerate
      diabetic myocardial fibrosis.

PMID- 24435584
TI  - Effects of a walking intervention using mobile technology and interactive voice
      response on serum adipokines among postmenopausal women at increased breast
      cancer risk.
AB  - Practical methods to reduce the risk of obesity-related breast cancer among high
      risk subgroups are lacking. Few studies have investigated the effects of exercise
      on circulating adipokines, which have been shown to be associated with obesity
      and breast cancer. The aim of this study was to examine the effects of a walking
      intervention on serum adiponectin, leptin, and the adiponectin-to-leptin ratio
      (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of
      developing breast cancer were stratified by BMI (25-30 kg/m(2) or >30 kg/m(2))
      and randomized to a 12-week, two-arm walking intervention administered through
      interactive voice response (IVR) and mobile devices. The intervention arms were
      IVR + coach and IVR + no-coach condition. Pre-post changes in serum adiponectin,
      leptin, and the A/L ratio were examined using mixed regression models, with ratio
      estimates (and 95 % confidence intervals [CI]) corresponding to postintervention
      adipokine concentrations relative to preintervention concentrations. While
      postintervention effects included statistically significant improvements in
      anthropometric measures, the observed decreases in adiponectin and leptin (ratio
      = 0.86, 95 % CI 0.74-1.01, and ratio = 0.94, 95 % CI 0.87-1.01, respectively) and
      increase in A/L ratio = 1.09, 95 % CI 0.94-1.26) were not significant. Thus,
      these findings do not support significant effects of the walking intervention on
      circulating adipokines among overweight and obese postmenopausal women.
      Additional studies are essential to determine the most effective and practical
      lifestyle interventions that can promote beneficial modification of serum
      adipokine concentrations, which may prove useful for obesity-related breast
      cancer prevention. 

PMID- 24435587
TI  - What an otolaryngologist should know about evaluation of a child referred for
      delay in speech development.
AB  - IMPORTANCE: Otolaryngologists are asked to evaluate children who a parent,
      physician, or someone else believes is slow in developing speech. Therefore, an
      otolaryngologist should be familiar with milestones for normal speech
      development, the causes of delay in speech development, and the best ways to help
      assure that children develop the ability to speak in a normal way. OBJECTIVE: To
      provide information for otolaryngologists that is helpful in the evaluation and
      management of children perceived to be delayed in developing speech. EVIDENCE
      ACQUISITION: Data were obtained via literature searches, online databases,
      textbooks, and the most recent national guidelines on topics including speech
      delay and language delay and the underlying disorders that can cause delay in
      developing speech. Emphasis was placed on epidemiology, pathophysiology, most
      common presentation, and treatment strategies. Most of the sources referenced
      were published within the past 5 years. RESULTS: Our article is a summary of
      major causes of speech delay based on reliable sources as listed herein.
      CONCLUSIONS AND RELEVANCE: Speech delay can be the manifestation of a spectrum of
      disorders affecting the language comprehension and/or speech production pathways,
      ranging from disorders involving global developmental limitations to motor
      dysfunction to hearing loss. Determining the cause of a child's delay in speech
      production is a time-sensitive issue because a child loses valuable opportunities
      in intellectual development if his or her communication defect is not addressed
      and ameliorated with treatment. Knowing several key items about each disorder can
      help otolaryngologists direct families to the correct health care provider to
      maximize the child's learning potential and intellectual growth curve.

PMID- 24435586
TI  - Double reporting and second opinion in head and neck pathology.

PMID- 24435588
TI  - Five metal-organic frameworks from 3,4-dimethylphenyl substituted imidazole
      dicarboxylate: syntheses, structures and properties.
AB  - Five metal-organic frameworks, namely, [Mn3(H2DMPhIDC)2(HDMPhIDC)2(bpp)]n
      (H3DMPhIDC = 2-(3,4-dimethylphenyl)-1H-imidazole-4,5-dicarboxylic acid, bpp = 1,3
      di(4-pyridyl)propane) (), [Pb4(DMPhIDC)2(OH)2]n (), [Cd(HDMPhIDC)(en)]n (en =
      ethylenediamine) (), [Cu3(HDMPhIDC)3(Py)3]n (Py = pyridine) () and
      {[Zn2(HDMPhIDC)2(Phen)2]2.H2O}n (Phen = 1,10-phenanthroline) () have been
      hydro(solvo)thermally synthesized and structurally characterized by single
      crystal X-ray diffraction, elemental and thermal analyses and IR spectra. Polymer
      displays a 3D noninterpenetrated framework with 1D open channels. Polymer
      exhibits a stepped (4,4,4,4,6,6)-connect 2D topology. Polymer is a left-handed
      helix chain. Polymers and arrange the 3D supramolecular networks containing a 1D
      corrugated chain via pipi stacking or hydrogen bond interactions. In these MOFs,
      the imidazole dicarboxylate ligand shows various coordination modes and strong
      coordination ability. Furthermore, the solid-state luminescent properties of the
      polymers have also been discussed. 

PMID- 24435589
TI  - Development of sexual behavior in free-ranging female Japanese macaques.
AB  - We studied the development of sexual behaviors in female Japanese macaques
      (Macaca fuscata) living at Arashiyama, Japan, in a group where adult females
      routinely exhibit sexual interactions with both males and females. Our cross
      sectional data on juvenile, adolescent, and adult females supported most of our
      predictions related to the learning hypothesis, which holds that adolescence
      serves to provide females with a period in which to practice adult female-like
      sexual behavioral patterns, including sexual solicitations, sexual mounts, and
      spatio-temporal coordination during consortships. We found evidence for a gradual
      acquisition of adult-like behavioral patterns (e.g., more frequent solicitations
      with body contact, more frequent complete mounts, more diverse solicitation
      patterns and complete mounting postures, and longer consortships involving
      prolonged inter-mount grasping behavior between partners), and a gradual
      disappearance of less effective immature behavioral patterns (e.g., less frequent
      non-contact solicitations, ambiguous mounting initiations, and incomplete
      mounts). We distinguished between three major categories of sexual behavioral
      patterns based on their speed of development, ranging from fast (e.g., diversity
      in mounting postures and genital stimulation during mounting) to slow (e.g.,
      contact solicitations and grasping behavior between consortship partners), with
      some being intermediate (e.g., range of solicitation patterns and expression of
      complete mounts). This study showed that the emergence of both conceptive and non
      conceptive adult sexual behaviors can be traced back to immature behavioral
      patterns in adolescent female Japanese macaques, with a major threshold occurring
      at the age of 4 years.

PMID- 24435592
TI  - Synthesis of polysubstituted pyrroles via [3 + 2]-annulation of aziridines and
      beta-nitroalkenes under aerobic conditions.
AB  - Polysubstituted pyrroles were regioselectively synthesized in moderate to good
      yields via the copper acetate-catalyzed [3 + 2] annulation reaction of readily
      accessible aziridines and nitroalkenes. This reaction was proposed to proceed
      through a key azomethine ylide intermediate generated by selective C-C bond
      cleavage of the aziridine followed by annulation with nitroalkenes under aerobic
      conditions. 

PMID- 24435590
TI  - Insights and advances in post-traumatic headache: research considerations.
AB  - Despite the growing awareness of mild traumatic brain injury in military and
      civilian populations, understanding of the acute and chronic effects of
      concussion on central nervous system structure and function is limited. Even less
      is understood about the underpinnings of the cardinal postconcussive symptom,
      post-traumatic headache (PTH). Here, we review recent advances in PTH, with
      special emphasis on the migraine-like phenotype, the most disabling form.
      Considerations for future research in PTH are discussed, including diagnostic
      classification, and applications with advanced neuroimaging techniques,
      biomarkers, and treatments. 

PMID- 24435591
TI  - Recent advances in myotonic dystrophy type 2.
AB  - Myotonic dystrophy is the commonest adult muscular dystrophy. Myotonic dystrophy
      type 1 (DM1) and myotonic dystrophy type 2 (DM2) are often discussed jointly, and
      although they share many clinical and molecular features, differences do exist.
      Historically, more is known about DM1 than about DM2. The literature in the field
      of myotonic dystrophy is broad, with advances in our understanding of DM2. This
      article reviews recent developments in DM2 with respect to diagnosis, systemic
      features, and molecular mechanisms of the disease.

PMID- 24435593
TI  - A quality improvement initiative to achieve high nursing presence during patient-
      and family-centered rounds.
AB  - OBJECTIVES: The objectives of this study were to: (1) identify local barriers to
      nursing presence on patient- and family-centered rounds (PFCR); and (2) increase
      nursing attendance during PFCR. METHODS: An electronic survey needs assessment
      was administered to nursing staff on a single acute medical care unit to identify
      local barriers to nursing presence on PFCR. Daily tracking of nursing presence on
      rounds was then performed over a 7-month period. During this time period, 2 Plan
      Do-Study Act cycles were conducted. The first intervention was a workshop for
      nurses about PFCR. The second intervention was the development of a strategy to
      contact nurses by using a hands-free communication device so that nurses were
      notified when rounds were starting on their patients. To evaluate the impact of
      our interventions, a p-chart was generated for the outcome of average daily
      nursing attendance (%) on PFCR per week over the 7-month period. RESULTS: Two
      barriers identified on the survey were: (1) nurses were uncertain if physicians
      valued their input during PFCR; and (2) nurses were unsure when the physician
      team would be conducting rounds on their patients. On the p-chart, the average
      percentage of nursing attendance before interventions was 47%. After the nursing
      workshop, no change in the mean nursing attendance on PFCR was noted. After
      initiation of the hands-free contact strategy, nursing attendance on PFCR rose to
      80%. CONCLUSIONS: A nursing contact strategy using a hands-free device led to a
      sustained increase in nursing attendance during PFCR.

PMID- 24435594
TI  - Family-centered rounds: a decade of growth.

PMID- 24435595
TI  - Pediatric discharge content: a multisite assessment of physician preferences and
      experiences.
AB  - BACKGROUND AND OBJECTIVES: Professional medical societies endorse prompt,
      consistent discharge communication to primary care providers (PCPs) on discharge.
      However, evidence is limited about what clinical elements to communicate. Our
      main goal was to identify and compare the clinical elements considered by PCPs
      and pediatric hospitalists to be essential to communicate to PCPs within 2 days
      of pediatric hospital discharge. A secondary goal was to describe experiences of
      the PCPs and pediatric hospitalists regarding sending and receiving discharge
      information. METHODS: A survey of physician preferences and experiences regarding
      discharge communication was sent to 320 PCPs who refer patients to 16 hospitals,
      with an analogous survey sent to 147 hospitalists. Descriptive statistics were
      calculated, and chi2 analyses were performed. RESULTS: A total of 201 PCPs (63%)
      and 71 hospitalists (48%) responded to the survey. Seven clinical elements were
      reported as essential by >75% of both PCPs and hospitalists: dates of admission
      and discharge; discharge diagnoses; brief hospital course; discharge medications;
      immunizations given during hospitalization; pending laboratory or test results;
      and follow-up appointments. PCPs reported reliably receiving discharge
      communication significantly less often than hospitalists reported sending it
      (71.8% vs 85.1%; P < .01), and PCPs considered this communication to be complete
      significantly less often than hospitalists did (64.9% vs 79.1%; P < .01).
      CONCLUSIONS: We identified 7 core clinical elements that PCPs and hospitalists
      consider essential in discharge communication. Consistently and promptly
      communicating at least these core elements after discharge may enhance PCP
      satisfaction and patient-level outcomes. Reported rates of transmission and
      receipt of this information were suboptimal and should be targeted for
      improvement.

PMID- 24435596
TI  - Identifying families with limited English proficiency using a capture-recapture
      approach.
AB  - BACKGROUND AND OBJECTIVE: Health providers need reliable estimates of the number
      of families with limited English proficiency (LEP) to assess language need and
      language service provision. Hospitals often lack reliable language screening
      tools and fail to provide interpretation for LEP families. The objective of this
      study was to develop a simple audit tool to more accurately identify LEP patients
      and families. METHODS: We conducted a cross-sectional analysis of a retrospective
      cohort of patients admitted to a large pediatric hospital between July 1 and
      December 31, 2009. We used a "capture-recapture" approach to develop a simple
      audit tool to measure language screening, determine the rate of language
      interpretation, and estimate the number of LEP families. The captures were based
      on 2 independent sources: (1) language need identified at registration and (2)
      request for interpretation during hospital admission. Assuming a closed
      population, we estimated the number of LEP families missed by both captures.
      RESULTS: During the study period, 6887 patients were admitted for care. There
      were 948 LEP families identified at registration and 847 families received
      interpretation at least once during hospital admission. We determined that the
      "ascertainment corrected" number of LEP families was 1031 (95% confidence
      interval: 1022-1040). The number of patients who had been "missed" by both
      methods was 15 (95% confidence interval: 7-24). Only 76% of LEP patients were
      identified in both data sources. CONCLUSIONS: A simple language audit tool can be
      used to determine language need, rates of interpretation, and unmet demand for
      language services, even when both sources of data are incomplete.

PMID- 24435598
TI  - Still lost in translation.

PMID- 24435597
TI  - Postoperative pain management in children, parental English proficiency, and
      access to interpretation.
AB  - BACKGROUND AND OBJECTIVE: Patients with limited English proficiency (LEP) are at
      risk for undertreated pain. The goal of this study was to examine the association
      between parental language proficiency, interpreted care, and postsurgical
      pediatric pain management. METHODS: This was a retrospective matched cohort study
      among children <18 years of age. Children of LEP and English-proficient (EP)
      parents were matched according to age group, surgical procedure, and admission
      date. Mean number of daily pain assessments and mean daily pain scores were
      compared between language groups. We also compared the association between pain
      scores and type of medication given (opioid versus nonopioid). Within the LEP
      group, similar analyses compared pain assessment and treatment of children whose
      families received >= 2 professional interpretations per day versus those who
      received lower rates of interpretation. RESULTS: A total of 474 children (237 LEP
      and 237 EP) were included in the study. Children of LEP parents had fewer pain
      assessments (mean: 7 [95% confidence interval: 2-13] vs 9 [95% confidence
      interval: 4-15]; P = .012), and higher levels of pain recorded before receiving
      opioid analgesics, compared with children of EP parents (P = .003). Within the
      LEP group, children with >= 2 interpretations per day had lower pain scores after
      medication administration (P < .05) and were more likely to receive opioids at
      pain levels similar to those of EP families. CONCLUSIONS: Children of LEP parents
      received fewer pain assessments and were less likely to receive opioid analgesics
      for similar levels of pain compared with children of EP parents. More frequent
      use of professional interpreters when assessing pain may aid in reducing the gap
      in pain management between LEP and EP pediatric patients.

PMID- 24435599
TI  - Appropriateness of testing for serious bacterial infection in children
      hospitalized with bronchiolitis.
AB  - OBJECTIVE: The goal of this study was to evaluate provider practice patterns for
      evaluation of serious bacterial infection (SBI) in patients hospitalized with
      bronchiolitis and to assess the association of SBI testing with length of stay
      and antibiotic use. DESIGN: This was a retrospective chart review of hospitalized
      patients <24 months of age with a discharge diagnosis of bronchiolitis from 2
      separate study sites during 2004 to 2008. Patient characteristics, laboratory
      testing, antibiotic use, and clinical outcomes were assessed in relation to SBI
      testing. RESULTS: A total of 1233 charts met inclusion criteria. The incidence of
      urinary tract infections in patients who underwent urine testing was 2.3%. Of the
      367 patients undergoing blood culture testing, all 13 positive-result blood
      cultures were contaminated specimens. There were no cases of meningitis. In
      total, 64.5% of patients tested for SBI had a blood culture obtained, 45.0% had
      an urinalysis or urine culture, and 16.3% had a cerebral spinal fluid culture
      obtained. Of those patients who underwent SBI testing, 53.8% received antibiotics
      versus 19.1% who did not (P < .0001). Length of stay for patients undergoing SBI
      testing was 3.4 days versus 2.3 days for those without SBI testing (P < .0001).
      There was no significant difference in readmission rates. CONCLUSIONS: SBI is
      uncommon in children hospitalized for bronchiolitis, and urinary tract infection
      is the most common diagnosis. In the evaluation of SBI in bronchiolitis,
      providers more frequently obtain blood cultures than urinalysis and/or urine
      cultures. Evaluation for SBI is associated with increased antibiotic use and
      increased LOS.

PMID- 24435600
TI  - Pediatric case reports: assessing recommendations from journals' instructions to
      authors.
AB  - BACKGROUND: Case reports (CRs) can be valuable contributions to medical knowledge
      and education. Objective assessments of publication potential and content
      recommendations for pediatric CRs are lacking. METHODS: The "Instructions to
      Authors" provided by pediatric journals were assessed to determine journal
      characteristics, manuscript restrictions, and advice to writers. Pediatric
      journals referenced in the National Center for Biotechnology Information
      databases were identified by using the search term "pediatric." Further inclusion
      criteria were: active journals; currently indexed in the PubMed, Ovid, and/or
      Medline databases; and English as the primary language. RESULTS: Sixty-nine (52%)
      of 132 pediatric journals surveyed published CRs per their author instructions.
      The median 2011 impact factor for accepting journals was 1.28 (range: 0.47-5.44)
      compared with 2.40 (range: 0.59-5.50) for journals that did not publish CRs (P <
      .001). Twelve (67%) of 18 pediatric surgical specialty journals, 16 (55%) of 29
      general pediatric journals, and 38 (51%) of 74 nonsurgical pediatric subspecialty
      journals published CRs. Sixteen journals had a separate Images section. Twenty
      five (36%) of 69 journals provided no recommendations. Of the 44 journals that
      did provide recommendations, new insights/observations (64%) was the most common
      content recommendation, followed by clinical relevance (41%), novelty/rarity
      (39%), and instructive/educational value (32%). CONCLUSIONS: Approximately one
      half of pediatric journals surveyed published CRs per their author instructions.
      Journals with lower impact factors were more likely to publish CRs. Many journals
      had specific formatting criteria. New insights and observations regarding
      relatively known pathology was the content criteria most often recommended.

PMID- 24435601
TI  - Route and length of therapy of acute uncomplicated hematogenous osteomyelitis: do
      we have the answers yet?

PMID- 24435602
TI  - It doesn't have to be evidense.

PMID- 24435603
TI  - Social media and pediatric hospital medicine: how our discipline benefits from a
      virtual community and why it matters for our future.

PMID- 24435604
TI  - Stevens-Johnson syndrome, mucositis, or something else?

PMID- 24435605
TI  - Ginger or Mary Ann? time to choose, professor.

PMID- 24435606
TI  - "Nobody does nothing better than a hospitalist".

PMID- 24435607
TI  - Section on hospital medicine leadership and staff.

PMID- 24435608
TI  - An appreciation for your support.

PMID- 24435609
TI  - A Psychiatric Residency Curriculum About Gender and Women's Issues.
AB  - Over the last 30 years, major advances have been made in our understanding of how
      bio-logical factors and sociocultural influences contribute to gender
      differences, gender identity formation, and gendered role behavior. Sensitivity
      to the psychological effects of changing family structure and workforce
      composition, the contribution of reproductive events, and the high rates of
      exposure to trauma in women is essential for optimal psychiatric assessment and
      treatment planning. This knowledge has not been systematically integrated into
      residency training. The authors present an outline for a curriculum in gender and
      women's issues, including educational objectives, learning experiences through
      which residents could meet these objectives, and recommended readings. The
      authors also discuss potential obstacles and suggest helpful strategies for
      implementing the proposed curriculum. 

PMID- 24435610
TI  - The neuroscience perspective and the changing role of the psychiatrist : the
      challenge for psychiatric educators.
AB  - The practice of psychiatry is undergoing rapid and radical changes because of
      health care reorganization and the advances in basic science. Therefore,
      psychiatric educators must confront the redefinition of the role of the
      psychiatrist in the health care system. The model of the psychiatrist who
      primarily provides office-based psychotherapy is outmoded. Rather, the
      psychiatrist must become a clinical expert in brain and behavioral sciences, with
      mastery over an expanding array of diagnostic techniques and responsibility for
      directing integrated multidisciplinary treatment and rehabilitative services. To
      ensure this expertise, students must receive a firm grounding in neuroscience,
      molecular genetics, and brain imaging in addition to the traditional curriculum. 

PMID- 24435611
TI  - Gay and lesbian issues in u.s. Psychiatry training as reported by residency
      training directors.
AB  - This study reports the results of a survey of U.S. residency training directors
      that explored the training milieu of gay and lesbian psychiatric residents. Of
      the 198 training directors surveyed, 134 (67.7%) completed the questionnaire. All
      but four of the directors reported the inclusion of gay and lesbian issues in the
      curriculum, most frequently in PGY-3. Using a 5-point rating scale, 47.3%
      reported that homosexuality was regarded at their programs as "normal" or
      "somewhat normal," 51.2% as "neutral," and 1.5% as "somewhat pathological" or
      "pathological." In general, the directors' overall assessment of departmental
      attitudes about homosexuality paralleled the findings previously reported by
      lesbian and gay residents, with some discrepancy concerning the disclosure of
      sexual orientation to psychotherapy patients. In the earlier study, nearly one
      third of gay and lesbian residents reported such disclosure; in the current
      study, only three training directors (2.5%) regarded this practice favorably. The
      results of the present study reflect the diversity of opinion found among
      residency training directors on the topic of gay and lesbian issues. 

PMID- 24435612
TI  - How many psychiatrists do we need?
AB  - Projections of manpower needs based on population growth and possibly improving
      access are unconvincing because of rapid changes in psychiatric practice and
      because complex social and political forces are influencing the psychiatrist's
      role in the mental health system. Given this basic uncertainty, attempts at
      filling residency positions at all costs are less than responsible. To serve our
      field well, efforts should be focused on recruiting "the best and the brightest"
      of our medical students and on providing quality training that stays in tune with
      the developments of the field and the evolution of the role of the psychiatrist. 

PMID- 24435613
TI  - Psychiatry and Family Medicine: Better Training is the Key to Better Professional
      Cooperation.

PMID- 24435615
TI  - Further insights into biological evaluation of new anti-Trypanosoma cruzi 5
      nitroindazoles.
AB  - Twelve molecules from a series of 35 new 5-nitroindazole derivatives, selected
      from a successful primary screening on Trypanosoma cruzi epimastigotes, have been
      evaluated against intracellular amastigotes according to the previous results of
      their trypanocidal activity and unspecific cytotoxicity. 2-Benzyl-1-propyl (22),
      2-benzyl-1-isopropyl (23), and 2-benzyl-1-butyl (24) 5-nitroindazolin-3-ones have
      inhibited the growth of amastigotes similarly to the reference drugs benznidazole
      and nifurtimox, inducing complete growth inhibition at concentrations lower than
      8 MUM (IC50 < 5 MUM) and accomplishing great selectivity indexes on the
      intracellular form of the parasite (SI > 30). Further in vivo assays were
      developed only for two of the most active molecules (22 and 24), reaching
      significant reductions in parasitemia levels (52 % and 77%, respectively) after
      their oral administration to infected mice. In addition, none of the mice in
      experimental and benznidazole groups died, unlike in the control group which is
      only treated with the vehicle. The trypanocidal properties found in some of the 5
      nitroindazole derivatives assayed in the present work represent an interesting
      contribution to the urgent need for searching new antichagasic drugs.

PMID- 24435616
TI  - Aspects of situated cognition in embodied numerosity: the case of finger
      counting.
AB  - Numerical cognitions such as spatial-numerical associations have been observed to
      be influenced by grounded, embodied and situated factors. For the case of finger
      counting, grounded and embodied influences have been reported. However, situated
      influences, e.g., that reported counting habits change with perception and action
      within a given situation, have not been systematically examined. To pursue the
      issue of situatedness of reported finger-counting habits, 458 participants were
      tested in three separate groups: (1) spontaneous condition: counting with both
      hands available, (2) perceptual condition: counting with horizontal (left-to
      right) perceptual arrangement of fingers (3) perceptual and proprioceptive
      condition: counting with horizontal (left-to-right) perceptual arrangement of
      fingers and with busy dominant hand. Report of typical counting habits differed
      strongly between the three conditions. 28 % reported to start counting with the
      left hand in the spontaneous counting condition (1), 54 % in the perceptual
      condition (2) and 62 % in the perceptual and proprioceptive condition (3).
      Additionally, all participants in the spontaneous counting group showed a
      symmetry-based counting pattern (with the thumb as number 6), while in the two
      other groups, a considerable number of participants exhibited a spatially
      continuous counting pattern (with the pinkie as number 6). Taken together, the
      study shows that reported finger-counting habits depend on the perceptual and
      proprioceptive situation and thus are strongly influenced by situated cognition.
      We suggest that this account reconciles apparently contradictory previous
      findings of different counting preferences regarding the starting hand in
      different examination situations.

PMID- 24435617
TI  - Heritabilities of intraocular pressure in the population of Korea: the Korean
      National Health and Nutrition Examination Survey 2008-2009.
AB  - IMPORTANCE: Intraocular pressure (IOP) is the principal modifiable risk factor
      for the progression of primary open-angle glaucoma. Studies that have measured
      the IOP directly in large numbers of matched parent-offspring pairs are limited
      in Asian populations. OBJECTIVE: To compare IOPs in parents and their offspring
      in Korea. DESIGN, SETTING, AND PARTICIPANTS: Family-based cohort study examining
      data from the Korean National Health and Nutrition Examination Survey conducted
      between 2008 and 2009. Data were obtained from 9700 participants from Korea. MAIN
      OUTCOMES AND MEASURES: Familial correlations for IOP were calculated in different
      types of relative pairs. Variance component methods were used to obtain
      heritability estimates. The individuals were stratified into 2 groups (those with
      and those without an IOP of >= 19 mm Hg; ie, high IOP group and nonhigh IOP
      group) based on the mean plus 2 SD IOP value of the entire study population. We
      evaluated the impact of parents' high IOP on offspring's high IOP. The
      relationship between parental systemic disease and high IOP in their offspring
      was also investigated. RESULTS: The mean (SD) IOPs in the right and left eyes
      were 13.90 (2.74) and 13.89 (2.74) mm Hg, respectively. Correlation coefficient
      estimates between parent-offspring pairs, sibling pairs, and spouse pairs for IOP
      were significant as 0.19, 0.31, and 0.29 (P < .001, P = .001, and P < .001,
      respectively). The total variance of the phenotype under study was explained by 2
      sources of variation, additive genetic (36% [95% CI, 32%-40%]) and unique
      environment (64% [95% CI, 60%-68%]). The risks of high IOP conferred by parents'
      high IOP were found to be significant for participants whose parents had high IOP
      (odds ratio, 9.76 [95% CI, 2.16-44.12]). In this study, high IOP was not
      associated with parental diabetes mellitus, hypertension, obesity, or metabolic
      syndrome. CONCLUSIONS AND RELEVANCE: Intraocular pressure showed a significant
      heritable tendency from parents to their offspring with a heritability estimate
      of 0.36 in Asian populations. The risk of high IOP was significantly increased in
      participants whose parents had high IOP. This has potential implications for the
      screening of family members of patients with ocular hypertension and glaucoma.

PMID- 24435619
TI  - A further evaluation of behavioral skills training for implementation of the
      picture exchange communication system.
AB  - We evaluated the effectiveness of a behavioral skills training package to teach
      implementation of Phases 1, 2, and 3A of the picture exchange communication
      system (PECS) to teachers employed at a therapeutic center for children with
      autism. Probes in the natural environment and follow-up were conducted with
      children who were assigned to work with the teachers in their own classrooms.
      Results provide additional support for the efficacy of behavioral skills training
      to teach implementation of PECS. 

PMID- 24435618
TI  - Bedside monitoring of ventilation distribution and alveolar inflammation in
      community-acquired pneumonia.
AB  - It is unclear whether bedside monitoring tools such as exhaled nitric oxide
      measurements (FENO) and electrical impedance tomography (EIT) could help guiding
      patient management in community-acquired pneumonia (CAP). We hypothesized that
      exhaled NO would be increased in CAP patients and could be used to assess
      resolution of inflammation in the course of CAP therapy. Feasibility of multiple
      breath (mb) and single-breath (sb) approach has been investigated. EIT was
      compared with chest X-ray at admission and used to assess whether the
      inhomogeneous ventilation changes due to treatment. 24 CAP patients were
      enrolled. Measurements were accomplished at admission (T0: EIT + FENO), after 3
      days (T1: FENO) and 5-6 days after admission (T2: EIT + FENO). We computed an EIT
      distribution index (DEIT), which reflects the uniformity of ventilation. FENO
      measurements showed a significant decrease in NO after the beginning of
      antibiotic therapy [p = 0.04 (sb); p = 0.003 (mb)]. Correlation between sb method
      and mb method was significant (p < 0.001, r = 0.70). EIT detects right-sided and
      left-sided ventilation disorders due to pneumonia in correspondence to chest X
      ray (p < 0.01). EIT images at T2 showed a more homogeneous ventilation
      distribution in displayed EIT. FENO could be a prospective supplementary tool to
      describe local lung inflammation as individual trend parameter. EIT could be a
      suitable supplementary tool to monitor functional lung status in CAP. 

PMID- 24435621
TI  - Effects of azathioprine and infliximab on mesenchymal stem cells derived from the
      bone marrow of rats in vitro.
AB  - Mesenchymal stem cell (MSC) transplantation has been demonstrated to be promising
      in the treatment of inflammatory bowel disease (IBD). Azathioprine (AZA) is
      widely used in IBD patients. Infliximab, as a representative of biological
      therapy for IBD, is important in the treatment regimen. In the present study we
      investigated the effects of AZA and infliximab on the cell proliferation, cell
      cycle and apoptosis of the MSCs derived from the bone marrow of Sprague-Dawley
      (SD) rats in vitro in order to provide preliminary data for optimizing the
      treatment of IBD. MSCs derived from the bone marrow of rats were either cultured
      in various concentrations of AZA- or infliximab-supplemented medium for 24, 48
      and 72 h, respectively. The growth curves of MSCs were obtained. The apoptosis
      and the cell cycle of the MSCs were analyzed by flow cytometry. AZA decreased the
      proliferation of MSCs by 66% and increased apoptosis at 0.20 mg/ml for 72 h
      (P<0.05). The percentage of necrotic cells increased markedly in MSCs treated
      with 0.30 mg/ml AZA for 72 h (P<0.05). As the exposure time increased, the
      percentage of MSCs in phase G0-G1 increased and that in phase S decreased in AZA
      groups exceeding 0.20 mg/ml (P<0.05). However, infliximab had a minimal impact on
      the cell proliferation, apoptosis and cell cycle of the MSCs. AZA was able to
      inhibit cell proliferation and induce apoptosis of the MSCs in vitro. Infliximab
      did not affect the cell proliferation, apoptosis and cell cycle of the MSCs
      derived from rats.

PMID- 24435622
TI  - [Competition in Antirrhinum majus L].
AB  - In Antirrhinum majus selection in the haplophase is investigated, using the
      segregation in the backcrossprogeny of heterozygotes cae/+(cae)(color of petal
      spot).An attempt was made to determine whether the competition depends on gene
      action of the locus caeca itself or on a gametophytic gene located in the same
      chromosome. Three types of progenies can be distinguished: Normal mendelian
      segregation, or statistically significant deviations with a surplus of "yellow
      spot" or a surplus of "light, nearly colorless spot" respectively. The hypothesis
      of an action of the locus cae in the haplophase can be rejected on the basis of
      these data.The location of a gametophytic gene in the gram-chromosome is assumed.
      The allele ga (+) comes from the line fim del cae, the allele ga (-)from the
      standard line S 50. Gametes with the allele ga (+)have a greater chance for
      fertilization than gametes with ga (-). The competition is found in the progeny
      of pollen and of egg cells. Two explanations are possible: one gene, which acts
      in the haplophase irrespective of the sex, or two closely coupled loci, which act
      in a similar way in the haplophase of each sex respectively. The locus ga is
      located either between cae and del or distal from cae. 

PMID- 24435623
TI  - Comparison of growth curves of mice selected and unselected for postweaning gain.
AB  - Mice were sampled from a line selected for increased postweaning weight gain from
      three to six weeks and from a randombred control line originating from the same
      base population. Body weights were recorded at each of 14 ages from day 5 to day
      98. The Richards and logistic growth functions were fitted to the growth
      trajectories of each individual mouse by a generalized non-linear least squares
      procedure. Estimated growth parameters (asymptotic weight, rate, shape of curve,
      age and weight at inflection, mean absolute growth rate and mean relative growth
      rate) were computed for each individual. The effects of line, litter within line,
      sex and line * sex interactions on these estimated parameters were then
      studied.Both the Richards and logistic functions fitted the data equally well and
      the plotted trajectories coincided over most of the growth curve. There was
      excellent agreement between the estimates of asymptotic weight and both age and
      weight at inflection based on the different functions. However, both functions
      apparently underestimated the asymptotic weight.Analyses of the line differences
      showed that selection for postweaning gain increased the mean absolute growth
      rate over the entire curve but had no effect on the relative growth rate or the
      shape of the growth curve. Full-sib analyses suggested the presence of
      considerable genetic variation and some high genetic correlations among the
      estimated growth parameters. 

PMID- 24435624
TI  - Some characteristics of segregation in hybrids of Hordeum spontaneum C. Koch
      emend. Bacht. * H. vulgare (L.) emend. Vav. et Bacht.
AB  - The analysis of hybrid generations, that had arisen from crosses of various forms
      of H. spontaneum, as well as comparison of the results of crossing
      representatives of H. spontaneum with two and six-row forms of H. vulgare warrant
      the following statements: 1. When various morphological races of H. spontaneum
      were intercrossed, no morphologically new types arose among the progeny of hybrid
      generations as a result of these crosses. Various morphological hybrid groups,
      eight up to F 3, remained strictly within the variability of the system of the
      species Hordeum spontaneum C. Koch emend. Bacht. 2. When various morphological
      races of H. spontaneum were hybridized with two- and six-row forms of H. vulgare,
      marked dominance of characters of the wild parent were observed, nevertheless
      even in F 3 occasional hybrid individuals with a nonbrittle ear have been
      obtained. This fact is an evidence that cultivated barley may take part in the
      formation of such hybrids. In the fourth generation of the above interspecific
      crosses besides individuals which had inherited the characters of one or the
      other of the parents new morphological types arise. The latter are characterized
      by new combinations, inherited from both parents. In studies reported previously
      such casual hybrid individuals were provisionally named by us
      "sessiliproskowetzii". At first glance, the latter seemed not to differ from H.
      spontaneum v. proskowetzii, but more thorough observation showed that such
      hybrids differ from genuine individuals of v. proskowetzii: their sterile lateral
      spikelets are sessile, i.e. deprived of pedicels. 

PMID- 24435625
TI  - The course of the first meiotic prophase in Beta procumbens and in the F1 between
      B. vulgaris and B. procumbens.
AB  - The succession of the stages of the first meiotic prophase in Beta procumbens has
      been ascertained by measurements of the nuclear volume and by other criteria. By
      this method it has been possible to relate the appearance of pairing gaps to the
      beginning separation of the chromosomes after pachytene. A zygotene-like stage of
      early diplotene has been found. Asynchronous condensation of the bivalents and
      reduction of the chiasma frequency have been observed in diplotene and
      diakinesis. - The lengths and arm ratios of the pachytene chromosomes of Beta
      procumbens were determined.Stages similar to those in B. procumbens have been
      recognized in the F 1 hybrid between Beta vulgaris and Beta procumbens. The
      pachytene chromosomes appeared to be paired to a great extent. However, only some
      of the cells showed bivalents in diakinesis, in the majority desynapsis occurred
      during diplotene or early diakinesis. In metaphase I, bivalents, univalents,
      cases of secondary association due to stickiness and cases of fragmentation have
      been observed. 

PMID- 24435626
TI  - Genotype - hatch interactions as a source of bias in estimating genetic
      components of variance for eight-week weight in poultry.
AB  - Data on 16,557 chicks from 198 sire groups were analyzed to determine the
      importance of genotype-hatch interactions as sources of bias in the estimation of
      genetic parameters for eight-week weight in poultry. Estimates of heritability
      for eight-week weight obtained from a paternal half-sib correlation were .27+/
      .04 and .29+/-.04 for males and females respectively when the sire component of
      variance was unconfounded with the sire-hatch interaction variance. If the sire
      hatch interaction effects were confounded with the sire effects in an intra-hatch
      analysis the corresponding estimates of heritability would be .30 and .35 for
      males and females respectively. No attempt was made to artificially create
      differences in the hatch environments.The ratio of the dam-hatch interaction
      variance to the dam component of variance as compared with the sire-hatch
      interaction variance to the sire component gave a slight indication of a greater
      degree of importance of the interaction of non-additive genetic-environment
      effects than additive x environmental effects in the male progeny but not in the
      female progeny. 

PMID- 24435627
TI  - Genetic correlation and response to selection in simulated populations : I.
      Additive model.
AB  - Effects of truncation selection of a primary trait upon genetic correlation with
      a secondary trait were examined over 30 generations in genetic populations
      simulated by computer. Populations were 24 males and 24 females mated randomly
      with replacement; number of offspring was determined by intensity of selection.
      Each trait was controlled by 48 loci segregating independently, effects were
      equal at every locus, and gene frequency was arbitrarily set at 0.5 at each locus
      in the initial generation. All combinations of three genetic correlations, three
      intensities of selection, and three environmental variances were simulated. Gene
      action was additive. Genetic correlation was set by number of loci which affected
      both traits and was measured each generation as the product-moment correlation of
      genotypic values and estimated by two methods of combining phenotypic covariances
      between parent and offspring.Genetic correlations in each offspring generation
      remained consistently near initial correlations for all environmental variances
      when fraction of offspring saved as parents was as large as one-half. When the
      fraction of offspring saved was as small as one-fifth, genetic correlations
      decreased but most rapidly with heritability high and after the 15th generation
      of selection. Truncation selection caused genetic correlation to decrease in
      those offspring selected to become parents of the next generation. Amount of
      reduction depended on heritability of the selected trait rather than on degree of
      truncation selection. Estimates of genetic correlation from phenotypic
      covariances between parent and offspring fluctuated markedly from real
      correlations in the small populations simulated. 

PMID- 24435628
TI  - [Investigations on the inheritance of self-fertility in rye (Secale cereale)].
AB  - The cross between the rye variety 'Petkuser Kurzstroh' and self-fertile plants of
      the North-American variety 'Dakold' was carried out and seed setting of the F 1
      generation and of the F 2- and F 3-generation produced by selfing was studied. In
      most cases seed setting was very high, only a few plants were self sterile, with
      fertile seeds ranging from 0-5 percent. Differences in the degree of fertility in
      the group of self-fertile plants are inherited and explained by subvital genes,
      which are not necessarily connected with the incompatibility system. To get more
      information on the inheritance of the self-fertility introduced by the variety
      'Dakold' pollen tube growth after selfing and crossing within the progenies was
      studied with the help of the petri dish technique. On the basis of the results it
      is concluded that self-fertility is not caused by an allele of one of the
      incompatibility loci but by a third factor. Synergic action of this factor with
      the incompatibility genes and the possible interaction between the alleles of the
      incompatibility loci of the two different parents are discussed. 

PMID- 24435629
TI  - Gamete selection with an inbred tester.
AB  - A common inbred tester was used to evaluate gametes selected from three complex
      hybrid populations using two different inbreds as elite lines. The results
      support STADLER'S contention that gamete selection is an efficient method for
      extracting superior gene combinations from hybrid populations. The inbred tester
      increases the resolving power of the method by eliminating extraneous genetic
      variability and by providing a homogeneous check population for comparative
      purposes. 

PMID- 24435630
TI  - Synthesis, biophysical studies and RNA interference activity of RNA having three
      consecutive amide linkages.
AB  - RNA sequences having up to three consecutive internal amide linkages were
      synthesized and studied using UV and NMR spectroscopy. The amide modifications
      did not interfere with normal base-pairing and A-type RNA conformation. Three
      consecutive amides were well tolerated in the passenger strand of siRNA and
      caused little change in RNAi activity. 

PMID- 24435631
TI  - Long-term effect of telmisartan on Alzheimer's amyloid genesis in SHR-SR after
      tMCAO.
AB  - Telmisartan is expected to reduce not only the level of blood pressure but also
      neuroinflammation and neurotoxicity via pleiotrophic effects as a metabo-sartan.
      We examined the effects of telmisartan on Alzheimer's disease (AD) pathology in
      spontaneously hypertensive rat stroke resistant (SHR-SR) after transient middle
      cerebral artery occlusion (tMCAO) by giving either telmisartan at 0 (vehicle),
      0.3 mg/kg/day (low dose, with no reduction of blood pressure), or 3 mg/kg/day
      (high dose, with a significant reduction of blood pressure) p.o. from 3 months
      (M) of age, and performed immunohistological analysis at 6, 12, and 18 M of age.
      The numbers of amyloid beta (Abeta)-positive neurons in the cerebral cortex and
      hippocampus and senile plaque (SP) in the ipsilateral cerebral cortex
      progressively increased with age until 18 M in the SHR-SR after tMCAO. On the
      other hand, low-dose telmisartan significantly reduced the number of Abeta
      positive neuron as well as SP at 6, 12, and 18 M. High-dose telmisartan showed
      further reductions of the above AD pathology. The present study suggests that
      telmisartan reduced both intracellular Abeta and extracellular SP accumulations
      after tMCAO in SHR-SR, with a further improvement by combined BP lowering. Such a
      strong effect of telmisartan could provide a preventative approach for AD in post
      stroke patients with hypertension. 

PMID- 24435632
TI  - Contrast sensitivity with bifocal intraocular lenses is halved, as measured with
      the Freiburg Vision Test (FrACT), yet patients are happy.
AB  - BACKGROUND: As the desire for spectacle independence following cataract surgery
      grows, so does interest in the implantation of multifocal intraocular lenses.
      However, glare phenomena, reduced intermediate vision and loss of image quality
      are known problems associated with this new generation of lenses. We compared the
      functional results achieved by the implantation of the diffractive-refractive
      Acri.LISA 366D lenses to those achieved from implanting monofocal Acri.Smart 46LC
      lenses. METHODS: In a retrospective data analysis we followed ten patients who
      received bifocal intraocular lenses (Acri.LISA 366D) and ten patients who
      received monofocal intraocular lenses (Acri.Smart 46LC). Lenses were always
      implanted in both eyes. In each group we assessed visual acuity and contrast
      sensitivity with the Freiburg Vison Test (FrACT) at multiple distances ranging
      from 0.5 to 5 m. Additionally, we assessed near vision with the Birkhaeuser
      charts. We also evaluated photopic phenomena and patient satisfaction using a
      standardised questionnaire. One patient in the Acri.LISA group and six patients
      in the control group missed the recommended follow-up visits. RESULTS: We found
      good uncorrected distance and near visual acuity. Only three of nine patients
      wore glasses occasionally. Although their contrast sensitivity decreased by a
      factor of two compared to the control group, patients did not complain about
      visual disturbances. Patient satisfaction was predominantly high following
      Acri.LISA 366D implantation. CONCLUSIONS: With the Acri.LISA 366D, patients
      demonstrate excellent near and distance vision, albeit with reduced contrast
      sensitivity. Acri Lisa is a viable option in patients that do not want to depend
      on spectacles.

PMID- 24435633
TI  - Characterization of two chlorophyll b-deficient, azide-derived mutants of Hordeum
      vulgare cv. Maris Mink.
AB  - Two mutant lines of Hordeum vulgare cv. Maris Mink (designated RChl 46 and 47)
      deficient in chlorophyll b have been isolated following azide mutagenesis. Two
      major thylakoid membrane proteins of molecular weight 25 and 26 k daltons are
      absent from the mutant plants following analysis by SDS gel electrophoresis,
      presumably due to a lack of the light harvesting chlorophyll a/b complex. The
      photosynthetic capabilities of the wild type and mutant lines were very similar. 

PMID- 24435634
TI  - The relationship between the activity and the activation state of RuBP
      carboxylase and carbon exchange rate as affected by sink and developmental
      changes.
AB  - The purpose of this study was to explore if sink manipulations which affect leaf
      carbon exchange rate (CER) are mediated by ribulose 1,5-bisphosphate (RuBP)
      carboxylase activity. Tomato leaf (Lycopersicon esculentum Mill. cv. Vendor) RuBP
      carboxylase was assayed using a rapid extraction method. Over a diurnal period,
      leaf CER fluctuated independent of carboxylase activity. Differences in leaf CER
      induced by fruit pruning in one leaf-one cluster plants were not accompanied by
      changes in carboxylase activity.During leaf expansion, carboxylase activity and
      percent enzyme in the active form paralleled the increase and then decrease in
      leaf carbon exchange rate. Differences in leaf CER induced by root warming at
      ambient air temperature, were accompanied by parallel changes in carboxylase
      activity.These results suggest that modifications in leaf CER are not mediated
      exclusively through changes in carboxylase activity, but rather that
      modifications in carboxylase activity coincide with overall changes in leaf
      physiology and morphology in response to sink demand. 

PMID- 24435635
TI  - Characterisation of the effects of Antimycin A upon high energy state quenching
      of chlorophyll fluorescence (qE) in spinach and pea chloroplasts.
AB  - High energy state quenching of chlorophyll fluorescence (qE) is inhibited by low
      concentrations of the inhibitor antimycin A in intact and osmotically shocked
      chloroplasts isolated from spinach and pea plants. This inhibition is independent
      of any effect upon DeltapH (as measured by 9-aminoacridine fluorescence
      quenching). A dual control of qE formation, by DeltapH and the redox state of an
      unidentified chloroplast component, is implied. Results are discussed in terms of
      a role for qE in the dissipation of excess excitation energy within photosystem
      II. 

PMID- 24435636
TI  - Generation of oscillatory behavior in the Laisk model of photosynthetic carbon
      assimilation.
AB  - The metabolic pathways in photosynthesis are modelled as an interconnected series
      of chemical reactions representing the electron transfer system, the carbon
      reduction cycle and starch and sucrose synthesis according to the model of Laisk
      and Walker [Proc R Soc Lond 227, 281-302 (1986)]. The model is formulated as a
      set of non-linear differential equations using mass-action kinetics, and
      stimulated for transient behaviour using an interactive simulation language. The
      model responses to switched light demonstrate the existence of oscillatory
      behaviour, similar to that found experimentally in O2 evolution and chlorophyll
      fluorescence, and explain known transient behaviour. The model is also used to
      investigate the source of oscillatory behaviour in the phosphate translocator,
      and other transient phenomena associated with the cyclic electron transfer
      system. 

PMID- 24435637
TI  - Tetranitromethane modification of photosystem 2.
AB  - Inhibition of photosystem 2 by the peptide-modification reagent,
      tetranitromethane, has been investigated with spinach digitonin particles. In the
      presence of tetranitromethane, (1) the initial fluoresence yield is suppressed
      with a concomitant elimination of the variable component of fluorescence; (2) the
      optical absorption transient at 820 nm, attributed to P680(+), is greatly
      attenuated; (3) diphenylcarbazide-supported photoreduction of dichlorophenol
      indophenol is abolished; and (4) electron spin resonance Signal 2f and Signal 2s
      are eliminated. These results are consistent with multiple sites of modification
      in photosystem 2 by tetranitromethane, and suggest further that this reagent can
      inhibit charge stabilization in the reaction center. 

PMID- 24435638
TI  - Photoinactivation of delta-aminolevulinic acid dehydratase from maize by flavin
      mononuclotide.
AB  - The delta-aminolevulinic acid dehydratase activity was irreversibly inactivated
      by irradiation of the enzyme in presence of flavin mononucleotide. The loss of
      enzyme activity was dependent on time of irradiation, concentration of FMN and
      intensity of irradiance. It required oxygen and was markedly enhanced in heavy
      water. The presence of levulinic acid (a competitive inhibitor of delta-ALAD)
      during irradiation prevented the inactivation considerably indicating
      photooxidative damage at or near the active site. Superoxide dismutase, sodium
      benzoate and sodium formate offered no protection, but singlet oxygen quenchers
      like azide and tryptophan were effective. NADH, electron donor to excited
      flavins, also prevented the loss of enzyme activity. These results indicate that
      singlet oxygen produced by light absorption of FMN was responsible for the
      photooxidative inhibition of the enzyme. 

PMID- 24435639
TI  - Kinetics of oxidation of the bound cytochromes in reaction centers from
      Rhodopseudomonas viridis.
AB  - The initial oxidized species in the photochemical charge separation in reaction
      centers from Rps. viridis is the primary donor, P(+), a bacteriochlorophyll
      dimer. Bound c-type cytochromes, two high potential (Cyt c 558) and two low
      potential (Cyt c 553), act as secondary electron donors to P(+). Flash induced
      absorption changes were measured at moderate redox potential, when the high
      potential cytochromes were chemically reduced. A fast absorption change was due
      to the initial oxidation of one of the Cyt c 558 by P(+) with a rate of
      3.7*10(6)s(-1) (tau=270nsec). A slower absorption change was attributable to a
      transfer, or sharing, of the remaining electron from one high potential heme to
      the other, with a rate of 2.8*10(5)s(-1) (tau=3.5 MUsec). The slow change was
      measured at a number of wavelengths throughout the visible and near infrared and
      revealed that the two high potential cytochromes have slightly different
      differential absorption spectra, with alpha-band maxima at 559 nm (Cyt c 559) and
      556.5 nm (Cyt c 556), and dissimilar electrochromic effects on nearby pigments.
      The sequence of electron transfers, following a flash, is: Cyt c 556->Cyt c 559
      >P(+). At lower redox potentials, a low midpoint potential cytochrome, Cyt c 553,
      is preferentially oxidized by P(+) with a rate of 7*10(6)s(-1) (tau=140 nsec).
      The assignment of the low and high potential cytochromes to the four, linearly
      arranged hemes of the reaction center is discussed. It is concluded that the
      closest heme to P must be the high potential Cyt c 559, and it is suggested that
      a likely arrangement for the four hemes is: c 553 c 556 c 553 c 559P. 

PMID- 24435640
TI  - The rate of formation of P700(+)-A 0 (-) in photosystem I particles from spinach
      as measured by picosecond transient absorption spectroscopy.
AB  - Photosystem I particles containing 30-40 chlorophyll a molecules per primary
      electron donor P700 were subjected to 1.5 ps low density laser flashes at 610 nm
      resulting in excitation of the antenna chlorophyll a molecules followed by energy
      transfer to P700 and subsequent oxidation of P700. Absorbance changes were
      monitored as a function of time with 1.5 ps time resolution. P700 bleaching
      (decrease in absorbance) occurred within the time resolution of the experiment.
      This is attributed to the formation of (1)P700.(*) This observation was confirmed
      by monitoring the rise of a broad absorption band near 810 nm due to chlorophyll
      a excited singlet state formation. The appearance of the initial bleach at 700 nm
      was followed by a strong bleaching at 690 nm. The time constant for the
      appearance of the 690 nm bleach is 13.7+/-0.8 ps. In the near-infrared region of
      the spectrum, the 810 nm band (which formed upon the excitation of the
      photosystem I particles) diminished to about 60% of its original intensity with
      the same 13.7 ps time constant as the formation of the 690 nm band. The spectral
      changes are interpreted as due to the formation of the charge separated state
      P700(+)-A0 (-), where A0 is the primary electron acceptor chlorophyll a molecule.

PMID- 24435641
TI  - Beta defensin-1 gene polymorphisms and susceptibility to atypical squamous cells
      of undetermined significance lesions in Italian gynecological patients.
AB  - The role of the human beta-defensin 1 (hBD-1) in the susceptibility to the onset
      of the Atypical Squamous Cells of Undetermined Significance (ASCUS) lesion, in
      the presence or not of HPV infection, is still unknown. In the current study, the
      three functional single nucleotide polymorphisms (SNPs) -52G > A, -44C > G, and 
      20G > A at the 5' un-translated region (UTR) of DEFB1 gene, encoding hBD-1, were
      analyzed in ASCUS lesion gynecological patients and healthy women from the north
      east of Italy (Trieste). Cervical samples from 249 European-Caucasian women were
      collected, screened for HPV and cytologically evaluated; DEFB1 genotyping has
      been performed by direct sequencing. No significant differences were found for 
      52G > A, -44C > G, and -20G > A SNPs allele and genotype frequencies between
      women with and without ASCUS lesions. DEFB1 minor haplotypes were significantly
      more frequent in ASCUS lesion positive than negative women, associating with an
      increased risk of this type of lesion. When women were stratified according to
      HPV infection status, significant differences in the distribution of -52G > A SNP
      genotype frequencies were found: the presence of the A allele in the homozygous
      genotype A/A associated with a lower risk of developing ASCUS lesions in HPV
      negative women. DEFB1 minor haplotypes were also associated with an increased
      risk of developing ASCUS lesions, being significantly more frequent in HPV
      negative women with lesions, than without lesions. Although these results
      highlight the possible involvement of DEFB1, further studies are needed to
      support the role of DEFB1 in the modulation of the susceptibility to ASCUS
      lesions.

PMID- 24435642
TI  - ABC transporters coupled with the elevated ergosterol contents contribute to the
      azole resistance and amphotericin B susceptibility.
AB  - Most screening approaches produce compounds that target survival genes and are
      likely to generate resistance over time. Simply having more drugs does not
      address the potential emergence of resistance caused by target mutation, drug
      efflux pumps over-expression, and so on. There is a great need to explore new
      strategies to treat fungal infections caused by drug-resistant pathogens. In this
      study, we found that azole-resistant Candida albicans with CaCDR1 and CaCDR2 over
      expression is hypersensitive against amphotericin B (AmB) by our high throughput
      synergy screening (HTSS). In contrast, Deltacdr1 and Deltacdr2 knockout strains
      were resistant to AmB. Moreover, clinical isolates with increased expression of
      CaCDR1 and CaCDR2 demonstrated susceptibility to AmB, which can also synergize
      with the efflux pumps inducer fluphenazine (FPZ). Finally, the increased drug
      susceptibility to AmB in azole-resistant C. albicans with drug efflux pumps over
      expression was consistent with the elevated expression of CaERG11 and its
      associated ergosterols in clinical isolates. Our data implies that the level of
      ergosterol contents determines the susceptibility to azoles and AmB in C.
      albicans. Deep understanding of the above mechanisms would offer new hope to
      treat drug-resistant C. albicans.

PMID- 24435643
TI  - The significance of the initiation process parameters and reactor design for
      maximizing the efficiency of microbial fuel cells.
AB  - Microbial fuel cells (MFCs) can be used for electricity generation via
      bioconversion of wastewater and organic waste substrates. MFCs also hold
      potential for production of certain chemicals, such as H2 and H2O2. The studies
      of electricity generation in MFCs have mainly focused on the microbial community
      formation, substrate effect on the anode reaction, and the cathode's catalytic
      properties. To improve the performance of MFCs, the initiation process requires
      more investigation because of its significant effect on the anodic biofilm
      formation. This review explores the factors which affect the initiation process,
      including inoculum, substrate, and reactor configuration. The key messages are
      that optimal performance of MFCs for electricity production requires (1)
      understanding of the electrogenic bacterial biofilm formation, (2) proper
      substrates at the initiation stage, (3) focus on operational conditions affecting
      initial biofilm formation, and (4) attention to the reactor configuration.

PMID- 24435644
TI  - Effects of lipopolysaccharide-induced inflammation on the interstitial cells of
      Cajal.
AB  - Interstitial cells of Cajal (ICC) have recently been found to display phenotypic
      changes. The present study is designed to determine whether phenotypic changes
      occur in ICC associated with an inflammatory microenvironment and whether the ICC
      phenotype could be recovered after the discontinuation of inflammatory stimuli.
      Immunohistochemistry studies revealed that the functional ICC marker, c-kit, was
      markedly reduced in patients with Hirschsprung's disease (n = 34) compared with
      controls (n = 12), whereas another marker of ICC, CD34, was not altered
      significantly. Compared with the vehicle group (n = 6), intraperitoneal injection
      of lipopolysaccharide (LPS; 1.5 mg/kg) in mice (n = 6) significantly induced
      plasma tumor necrosis factor-alpha (TNF-alpha) levels as determined by enzyme
      linked immunosorbent assay. Western blot and real-time polymerase chain reaction
      assessment further showed that LPS injection markedly suppressed intestinal c-kit
      protein and mRNA expression, which could be blocked by Toll-like receptor 4
      (TLR4) deficiency (n = 6) rather than TLR2 deficiency (n = 6) and had no effects
      on CD34. Compared with the vehicle group (n = 6), intraperitoneal TNF-alpha (30
      MUg/kg) administration (n = 6) also significantly reduced intestinal c-kit
      protein and mRNA levels but not CD34 levels. However, the reduction of c-kit
      induced by TNF-alpha injection was not suppressed by TLR4 deficiency (n = 6).
      Intestinal c-kit protein and mRNA levels were markedly restored after the
      discontinuation of TNF-alpha administration for 7 days. Moreover,
      immunofluorescence analysis of primary ICC further confirmed that exposure to TNF
      alpha for 24 h suppressed c-kit expression, which could be restored after
      discontinuation of TNF-alpha exposure. CD34 expression was not altered upon
      exposure to TNF-alpha. Thus, phenotypic changes in ICC occur in an inflammatory
      microenvironment in the gut and LPS, TLR4 and TNFalpha are crucial to this
      process.

PMID- 24435646
TI  - Educational objectives for a junior psychiatry clerkship : development and
      rationale.
AB  - Explicit instructional objectives have become essential in medical education and
      have been developed nationally for students in surgery, gynecology, and pediatric
      clerkships. The authors describe the rationale for and process of developing
      psychiatry clerkship objectives, first at the Medical College of Pennsylvania
      (MCP) and then by the Association of Directors of Medical Student Education in
      Psychiatry. Faculty interviews about the development of psychiatry clerkship
      objectives at MCP illustrate the objectives' positive educational impact. 

PMID- 24435647
TI  - Student ratings of outpatient learning favor rural community mental health
      centers.
AB  - All students (N = 185) in 8 consecutive rotations within a private Southern
      schools multisite, inpatient-based psychiatry clerkship completed a survey of
      perceived educational experiences while assigned to 1 of 5 part-time outpatient
      services (usable response rate 82%). The rural community mental health center
      (CMHC) students reported increased 1) appreciation for the nature and
      implications of psychiatric disorders; 2) appreciation for treatment
      effectiveness; 3) interest, enjoyment, and hopefulness; 4) firsthand experience
      with patient evaluation and treatment; 5) community treatment resource
      information; and 6) teaching model helpfulness. The rural CMHC and Veterans
      Affairs Medical Center students reported a learning model based on experience.
      The rural CMHC and university student mental health service better exemplified
      the biopsycho-social treatment approach. 

PMID- 24435645
TI  - PECAM-1: regulator of endothelial junctional integrity.
AB  - PECAM-1 (also known as CD31) is a cellular adhesion and signaling receptor
      comprising six extracellular immunoglobulin (Ig)-like homology domains, a short
      transmembrane domain and a 118 amino acid cytoplasmic domain that becomes serine
      and tyrosine phosphorylated upon cellular activation. PECAM-1 expression is
      restricted to blood and vascular cells. In circulating platelets and leukocytes,
      PECAM-1 functions largely as an inhibitory receptor that, via regulated
      sequential phosphorylation of its cytoplasmic domain, limits cellular activation
      responses. PECAM-1 is also highly expressed at endothelial cell intercellular
      junctions, where it functions as a mechanosensor, as a regulator of leukocyte
      trafficking and in the maintenance of endothelial cell junctional integrity. In
      this review, we will describe (1) the functional domains of PECAM-1 and how they
      contribute to its barrier-enhancing properties, (2) how the physical properties
      of PECAM-1 influence its subcellular localization and its ability to influence
      endothelial cell barrier function, (3) various stimuli that initiate PECAM-1
      signaling and/or function at the endothelial junction and (4) cross-talk of PECAM
      1 with other junctional molecules, which can influence endothelial cell function.

PMID- 24435648
TI  - An integrated preclerkship curriculum in neuroscience, psychiatry, and neurology.
AB  - The study's objective was to promote understanding of the integration of
      preclerkship learning in neuroscience, psychiatry, and neurology and to share the
      authors' experience with such a program. A dualism, which may have survived in
      the past for lack of robust evidence of mind-brain relationships, is now
      increasingly outmoded. Medical school education should reflect the increasing
      coherence to be found in these fields. The authors describe curricular and course
      innovations and revisions at Harvard Medical School that have been implemented in
      successive iterations over the past decade. These changes have depended upon
      multidisciplinary leadership, planning, and faculty participation, as well as
      faculty development and closer coordination between classroom- and hospital-based
      activity. A hybrid, problem-based block course in the second year integrates
      basic science with neurologic and psychiatric topics that are aligned with
      practice of relevant clinical skills. The authors have achieved a high level of
      integration and coordination of these subjects at preclerkship levels in the
      domains of both knowledge and skills. The students, as well as the faculty,
      strongly endorse an intellectually coherent and clinically relevant program of
      integrated preclerkship learning in neuroscience, psychiatry, and neurology. 

PMID- 24435649
TI  - Evaluating psychiatric clinical clerks with a mini-objective structured clinical
      examination.
AB  - Although objective structured clinical examinations (OSCEs) are well-accepted
      performance-based assessments with good reliability, psychiatric educators have
      been slow to adopt this evaluation method, opting for oral exams that often have
      inferior psychometric properties. A 4-station "mini-OSCE" was developed and used
      to test 42 clinical clerks in psychiatry. The examination mean score and standard
      deviation were 74% and 8.08, respectively, while individual scores ranged from
      56% to 86%. Interstation reliability was 0.61. Student and faculty satisfaction
      was high. A "mini-OSCE" for psychiatric clinical clerks confers the benefits of
      acceptable reliability and a high degree of acceptance without incurring the high
      costs usually associated with OSCE evaluation. 

PMID- 24435650
TI  - Practice guidelines and psychiatric education : potential implications.
AB  - The American Psychiatric Association's practice guidelines provide authoritative
      guidance for assessing and treating major clinical problems that psychiatrists
      face. This article reviews the social context in which practice guidelines have
      emerged, opportunities they afford educators, and limitations in their
      educational and practice applications. Practice guidelines should be used in
      residents' and medical students' seminars and in continuing medical education
      activities. The incentive to study guidelines may increase as their likely use as
      information sources for questions on in-service and specialty board certification
      examinations as well as in clinical quality-assurance activities becomes more
      widely recognized. 

PMID- 24435651
TI  - An integrated preclerkship curriculum in neuroscience, psychiatry, and neurology.

PMID- 24435653
TI  - In vivo passage of human prostate cancer cells in mice results in stable gene
      expression changes affecting numerous cancer-associated biological processes.
AB  - BACKGROUND: While therapeutic resistance is difficult to model in vitro in its
      entirety, in vivo passage and re-derivation of treatment resistant prostate
      cancer cell variants is a strategy to study therapeutic resistance more
      comprehensively. However, the process of in vivo passage itself may result in
      gene expression changes that could confound the analysis of such resistant cell
      variants compared to their parental cell lines. METHODS: We compared the
      expression profiles of parental PC-3 human prostate cancer cells and PC-3 cells
      re-derived after in vivo passage in athymic nude mice. Whole transcriptome
      information was obtained using the SOLiD 4 system (Applied Biosystems).
      Differentially expressed genes were mapped to genes in the Database for
      Annotation, Visualization and Integrated Discovery for gene enrichment and
      functional annotation analysis. The expression of a panel of these genes was
      validated using quantitative RT-PCR. RESULTS: Altogether, 21,032 distinct
      transcripts were found in PC-3 and/or NS1.1. Of these, 906 were differentially
      regulated (>=2-fold) in NS1.1 versus PC-3. 337 transcripts were upregulated, and
      569 were downregulated, including genes previously associated with various
      aspects of prostate carcinogenesis such as TLR4 and IGFBP5, respectively. Gene
      ontology analysis of the differentially expressed transcripts revealed enrichment
      for biological processes such as cell adhesion, migration, and angiogenesis.
      CONCLUSIONS: When using in vivo as opposed to in vitro derived prostate cancer
      cell variants for comparative genetic studies of complex traits such as
      therapeutic resistance, one may be better served to use similarly in vivo
      passaged control cell variants instead of parental cell lines.

PMID- 24435654
TI  - Discovering the pivotal role of carbonate in the formation of a bis-phenolate
      supported Co15 cluster.
AB  - Unexpected panelling by MU6-CO3(2-) anions has been observed to support the
      formation of a new and unusual Co15 cluster. The arrangement is further
      stabilised by bis-phenolate ligands which assemble in a manner akin to
      tetrahomodioxacalix[4]arene. The reaction proceeds in very low yield as MU6-CO3(2
      ) anions are formed in situ, but targeted synthesis by addition of carbonate
      improves synthetic yield and highlights the pivotal role of this anion in the
      overall assembly process. 

PMID- 24435655
TI  - Overexpression of transferrin receptor CD71 and its tumorigenic properties in
      esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal
      cancer in endemic Asian regions. In the present study, we investigated the
      clinical implication and role of transferrin receptor CD71 in ESCC. CD71 has a
      physiological role in cellular iron intake and is implicated in the
      carcinogenesis of various types of tumors. In our cohort, more than a 2-fold
      upregulation of the CD71 transcript was detected in 61.5% of patients using
      quantitative polymerase chain reaction. Immunohistochemical analysis also showed
      strong membranous and cytoplasmic localization of CD71 in paraffin-embedded
      tumors. Staining parallel tumor sections with the proliferative marker Ki-67
      revealed that the pattern of Ki-67 staining was associated with CD71 expression.
      Analysis of clinicopathological data indicated that CD71 overexpression can be
      used as an indicator for advanced T4 stage (p=0.0307). These data suggested a
      strong link between CD71 and ESCC. Subsequent in vitro assays using short
      interfering RNA (siRNA) to suppress CD71 expression confirmed the tumorigenic
      properties of CD71 in ESCC; cell growth inhibition and cell cycle arrest at S
      phase were observed in CD71-suppressed cells. The underlying mechanism involved
      activation of the MEK/ERK pathway. In summary, the present study provides
      evidence showing the tumorigenic properties of CD71 in ESCC with clinical
      correlations and suggests targeting CD71 as a strategy for the treatment of ESCC.

PMID- 24435656
TI  - Cardiac fibroblasts support endothelial cell proliferation and sprout formation
      but not the development of multicellular sprouts in a fibrin gel co-culture
      model.
AB  - A primary impediment to cardiac tissue engineering lies in the inability to
      adequately vascularize the constructs to optimize survival upon implantation.
      During normal angiogenesis, endothelial cells (ECs) require a support cell to
      form mature patent lumens and it has been demonstrated that pericytes, vascular
      smooth muscle cells and mesenchymal stem cells (MSCs) are all able to support the
      formation of mature vessels. In the heart, cardiac fibroblasts (CFs) provide
      important electrical and mechanical functions, but to date have not been
      sufficiently studied for their role in angiogenesis. To study CFs role in
      angiogenesis, we co-cultured different concentrations of various cell types in
      fibrin hemispheres with appropriate combinations of their specific media, to
      determine the optimal conditions for EC growth and sprout formation through DNA
      analysis, flow cytometry and immunohistology. ECs proliferated best when co
      cultured with CFs and analysis of immunohistological images demonstrated that ECs
      formed the longest and most numerous sprouts with CFs as compared to MSCs.
      However, ECs were able to produce more multicellular sprouts when in culture with
      the MSCs. Moreover, these effects were dependent on the ratio of support cell to
      EC in co-culture. Overall, CFs provide a good support system for EC proliferation
      and sprout formation; however, MSCs allow for more multicellular sprouts, which
      is more indicative of the in vivo process. 

PMID- 24435657
TI  - Therapeutic magnetic microcarriers guided by magnetic resonance navigation for
      enhanced liver chemoembilization: a design review.
AB  - This review paper describes the past, present and future design of therapeutic
      magnetic carriers (TMMC) being guided in the vascular network using a novel
      technique known as magnetic resonance navigation (MRN). This targeting method is
      an extension of magnetic resonance imaging (MRI) technologies. MRN, based on
      magnetic gradient variation, aims to navigate carriers in real-time along a pre
      planned trajectory from their injection site to a targeted area. As such, this
      approach should minimize systemic distribution of toxic agents loaded into the
      carriers and improve therapeutic efficacy by delivering a larger proportion of
      the drug injected. MRN-compatible carriers (shape, material, size, magnetic
      properties, biocompatibility) have to be designed by taking into consideration
      the constraints of the medical task and MRN. In the past, as a proof of concept
      of MRN feasibility, a 1.5-mm ferromagnetic bead was guided in the artery of a
      living swine with a clinical MRI system. Present day, to aim at medical
      applications, TMMC have been designed for targeted liver chemoembolization by
      MRN. TMMC are 50-MUm biodegradable microparticles loaded with iron-cobalt
      nanoparticles and doxorubicin as an antitumor drug. TMMC were selectively guided
      to the right or left liver lobes in a rabbit model with a clinical MRI scanner
      upgraded with steering coils. To treat human liver tumor, according to the
      theoretical MRN model, future TMMC design should take into consideration magnetic
      nanoparticle properties (nature and loading), MRN platform performances (gradient
      amplitude and rise time) and vascular hepatic network properties (blood flow
      velocity and geometry) to optimize the carrier diameter for efficient
      chemoembolization. 

PMID- 24435658
TI  - Recent and future directions in CT imaging.
AB  - Computed tomography (CT) has made enormous technical advances since its
      introduction into clinical use. The engineering improvements have in turn led to
      important clinical applications and large impact in patient care. This paper
      reviews the technology development trends in CT since its introduction and uses
      these trends to help illuminate likely future progress. The prediction is that
      significant further improvements in speed, spatial resolution and dose efficiency
      can be expected in the next decade. 

PMID- 24435659
TI  - Human placental extract mediated inhibition of proteinase K: implications of
      heparin and glycoproteins in wound physiology.
AB  - Efficient debridement of the wound bed following the removal of microbial load
      prevents its progression into a chronic wound. Bacterial infection and excessive
      proteolysis characterize impaired healing and therefore, their inhibition might
      restore the disturbed equilibrium in the healing process. Human placental extract
      exhibits reversible, non-competitive inhibition towards Proteinase K, a microbial
      protease, by stabilizing it against auto-digestion. Scattering and fluorescence
      studies followed by biochemical analysis indicated the involvement of a glycan
      moiety. Surface plasmon resonance demonstrated specific interaction of heparin
      with Proteinase K having Kd in MUM range. Further, Proteinase K contains sequence
      motifs similar to other heparin-binding proteins. Molecular docking revealed
      presence of clefts suitable for binding of heparin-derived oligosaccharides.
      Comprehensive analysis of this inhibitory property of placental extract partly
      explains its efficacy in curing wounds with common bacterial infections.

PMID- 24435660
TI  - Effect of bifocal and prismatic bifocal spectacles on myopia progression in
      children: three-year results of a randomized clinical trial.
AB  - IMPORTANCE: Myopia is a significant public health problem, making it important to
      determine whether a bifocal spectacle treatment involving near prism slows myopia
      progression in children. OBJECTIVE: To determine whether bifocal and prismatic
      bifocal spectacles control myopia in children with high rates of myopia
      progression and to assess whether the treatment effect is dependent on the lag of
      accommodation and/or near phoria status. DESIGN, SETTING, AND PARTICIPANTS: This
      3-year randomized clinical trial was conducted in a private practice. A total of
      135 (73 female and 62 male) Chinese-Canadian children (aged 8-13 years; mean [SE]
      age, 10.29 [0.15] years; mean [SE] myopia, -3.08 [0.10] D) with myopia
      progression of at least 0.50 D in the preceding year were randomly assigned to 1
      of 3 treatments. A total of 128 (94.8%) completed the trial. INTERVENTIONS:
      Single-vision lenses (control, n = 41), +1.50-D executive bifocals (n = 48), and
      +1.50-D executive bifocals with 3-Delta base-in prism in the near segment of each
      lens (n = 46). MAIN OUTCOMES AND MEASURES Myopia progression (primary) measured
      using an automated refractor following cycloplegia and increase in axial length
      (secondary) measured using ultrasonography at intervals of 6 months for 36
      months. RESULTS Myopia progression over 3 years was an average (SE) of -2.06
      (0.13) D for the single-vision lens group, -1.25 (0.10) D for the bifocal group,
      and -1.01 (0.13) D for the prismatic bifocal group. Axial length increased an
      average (SE) of 0.82 (0.05) mm, 0.57 (0.07) mm, and 0.54 (0.06) mm, respectively.
      The treatment effect of bifocals (0.81 D) and prismatic bifocals (1.05 D) was
      significant (P < .001). Both bifocal groups had less axial elongation (0.25 mm
      and 0.28 mm, respectively) than the single-vision lens group (P < .001). For
      children with high lags of accommodation (>= 1.01 D), the treatment effect of
      both bifocals and prismatic bifocals was similar (1.1 D) (P < .001). For children
      with low lags (<1.01 D), the treatment effect of prismatic bifocals (0.99 D) was
      greater than of bifocals (0.50 D) (P = .03). The treatment effect of both
      bifocals and prismatic bifocals was independent of the near phoria status.
      CONCLUSIONS AND RELEVANCE: Bifocal spectacles can slow myopia progression in
      children with an annual progression rate of at least 0.50 D after 3 years. These
      results suggest that prismatic bifocals are more effective for myopic children
      with low lags of accommodation. TRIAL REGISTRATION clinicaltrials.gov Identifier:
      NCT00787579.

PMID- 24435661
TI  - 6-Pentyl-2H-pyran-2-one: a potent peach-derived kairomone for New Zealand flower
      thrips, Thrips obscuratus.
AB  - New Zealand flower thrips, Thrips obscuratus (Thysanoptera: Thripidae), are
      attracted to ripening fruits, especially peaches. Volatiles from unripe and ripe
      peach fruits were collected and analyzed by gas chromatography/mass spectrometry.
      Six lactones were found only in ripe peach volatiles: gamma-heptalactone, gamma
      octalactone, gamma-nonalactone, 6-pentyl-2H-pyran-2-one, gamma-decalactone, and
      delta-decalactone. When these compounds were tested individually in field
      trapping experiments, three of them (gamma-octalactone, gamma-nonalactone, and 6
      pentyl-2H-pyran-2-one) attracted New Zealand flower thrips. In another field
      trapping experiment, aimed at testing various combinations of the three active
      compounds, no synergistic effects were found among all combinations tested; no
      combination caught more thrips than 6-pentyl-2H-pyran-2-one, alone. A further
      field-trapping experiment was conducted to determine the dose (10, 100, and 500
      mg) of 6-pentyl-2H-pyran-2-one that gave the greatest catch of T. obscuratus,
      while also comparing it against another attractant, ethyl nicotinate, for T.
      obscuratus. The greatest catches in traps baited with either attractant were at
      loadings of 500 mg. At both 10 and 500 mg, traps baited with 6-pentyl-2H-pyran-2
      one caught more T. obscuratus than those baited with the same amounts of ethyl
      nicotinate. 6-Pentyl-2H-pyran-2-one is a potent attractant for New Zealand flower
      thrips and, therefore, could be used for monitoring and control of New Zealand
      flower thrips. Work is underway developing monitoring and control options
      utilizing 6-pentyl-2H-pyran-2-one for this important pest. 

PMID- 24435663
TI  - Retrospective analysis of the mutagenicity/genotoxicity data of the cosmetic
      ingredients present on the Annexes of the Cosmetic EU legislation (2000-12).
AB  - To evaluate the mutagenicity/genotoxicity of cosmetic ingredients at the
      regulatory level, usually a battery of three in vitro tests is applied. This
      battery, designed to be very sensitive, produces a high number of positive
      results, imposing the need for in vivo follow-up testing to clear the substance
      under study. In Europe, the use of experimental animals has become impossible for
      cosmetic ingredients due to the implementation of animal testing and marketing
      bans. Consequently, the possibility to 'de-risk' substances with positive in
      vitro results disappear and potentially safe cosmetic substances will be lost for
      the EU market unless currently used in vitro assays can be adapted or new non
      animal mutagenicity/genotoxicity studies become available. Described strategies
      to improve the specificity of existing in vitro assays include optimisation of
      the used cell type and cytotoxicity assay and lowering of the applied top
      concentration. A reduction of the number of tests in the battery from three to
      two also has been suggested. In this study, the performance of the 'standard' in
      vitro mutagenicity/genotoxicity testing battery is analysed for a number of
      cosmetic ingredients. We composed a database with toxicological information on
      249 cosmetic ingredients, mainly present on the Annexes of the European cosmetic
      legislation. Results revealed that the in vitro mutagenicity/genotoxicity tests
      showed a low specificity for the cosmetic ingredients concerned, comparable to
      the specificity published for chemicals. Non-confirmed or 'misleading' positive
      results amounted up to 93% for the in vitro test batteries. The cell type and top
      concentrations did not have a major impact on the specificity. With respect to
      cytotoxicity determinations, different end points were used, potentially leading
      to different testing concentrations, suggesting the need for a consensus in this
      matter. Overall, the results of this retrospective analysis point to an urgent
      need of better regulatory strategies to assess the potential
      mutagenicity/genotoxicity of cosmetic ingredients. 

PMID- 24435662
TI  - An increase of oxidised nucleotides activates DNA damage checkpoint pathway that
      regulates post-embryonic development in Caenorhabditis elegans.
AB  - 8-Oxo-dGTP, an oxidised form of dGTP generated in the nucleotide pool, can be
      incorporated opposite adenine or cytosine in template DNA, which can in turn
      induce mutations. In this study, we identified a novel MutT homolog (NDX-2) of
      Caenorhabditis elegans that hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP. In addition, we
      found that NDX-1, NDX-2 and NDX-4 proteins have 8-oxo-GTPase or 8-oxo-GDPase
      activity. The sensitivity of ndx-2 knockdown C. elegans worms to methyl viologen
      and menadione bisulphite was increased compared with that of control worms. This
      sensitivity was rescued by depletion of chk-2 and clk-2, suggesting that growth
      of the worms is regulated by the checkpoint pathway in response to the
      accumulation of oxidised nucleotides. Moreover, we found that the sensitivity to
      menadione bisulphite of ndx-1 and ndx-2-double knockdown worms was enhanced by
      elimination of XPA-1, a factor involved in nucleotide excision repair. The rescue
      effect by depletion of chk-2 and clk-2 was limited in the xpa-1 mutant,
      suggesting that the chk-2 and clk-2 checkpoint pathway is partially linked to the
      function of XPA-1. 

PMID- 24435664
TI  - Biochemical composition of maize (Zea mays L.) pollen : I. Effects of the
      endosperm mutants, waxy (wx), shrunken (sh 2) and sugary (su 1) on the amino acid
      content and fatty acid distribution.
AB  - Proline was the most abundant amino acid with a mean value of 186.28 MU moles/mg
      dry pollen. The other amino acids tested were below 33 MU moles/mg dry pollen.
      The mutant wx significantly increased aspartic acid, valine, histidine and an
      unknown but significantly decreased alpha aminobutyric acid. The mutant sh 2
      significantly increased glutamic acid, proline, lysine, histidine and an unknown
      but significantly decreased aspartic acid and alpha aminobutyric acid. The effect
      of su 1 was altered by the genetic background involved. In one genetic
      background, su 1 did not significantly increase any amino acid but significantly
      decreased alanine and alpha aminobutyric acid. However, in a distinctly different
      background, su 1 significantly increased alpha aminobutyric acid but
      significantly decreased aspartic acid and glutamic acid. Apparently the genetic
      background is capable of producing major shifts in the amino acid pattern in
      addition to the action of these mutants.The fatty acids, palmitic and linolenic
      were the most common with percentages of 54.1 and 34.4 respectively. The mutants
      tested did not affect the fatty acid distribution. 

PMID- 24435665
TI  - On the determination of relative fitness from frequencies of genotypes in
      subsequent generations : Part I. Algebra of reproduction and selection in
      populations with discrete generations.
AB  - An algebraic treatment of reproduction and selection processes in populations of
      diploids with discrete generation cycles is presented. The main objective was a
      determination of the conditions under which the selection coefficients for the
      various genotypes can be determined solely on the basis of known frequencies of
      genotypes in two subsequent generations. In part two, to be published later, the
      statistical properties of a special fitness estimator, proposed by Hayman, are
      considered. Confidence intervals and tests of significance concerning hypotheses
      about fitness are established and checked by computer simulation studies. 

PMID- 24435666
TI  - Peroxidases in the genus Nicotiana.
AB  - Leaf peroxidases of 60 Nicotiana species, 19 cultivars, autopolyploids,
      interspecific hybrids, and amphidiploids have been compared by polyacrylamide gel
      block electrophoresis. At least 19 peroxidase bands, four cathodic and 15 anodic,
      were detected in the species which varied from two bands in N. arentsii to 12
      bands in N. tabacum. Tihe cultivars of the latter species failed to reveal any
      intraspecific variation. Specific difference and varietal resemblance in root
      peroxidase bands were also observed in nine species and 20 varieties analyzed.
      Zymograms from autopolyploids and amphidiploids appeared to be identical to that
      of diploid parents, suggesting that peroxidase banding patterns are independent
      of ploidy levels. An additive manner of parental peroxidase bands without hybrid
      enzyme formation in interspecific hybrids and the failure of dissociating
      peroxidases into subunits lead to a hypothesis that peroxidases in Nicotiana may
      be controlled by multiple, dominant genes and/or codominant alleles in
      chromosomes of different genomes. This is in keeping with the lack of
      relationship between ploidy level and peroxidase banding pattern. Also, species
      with different chromosome numbers shared many peroxidases in common that possibly
      reflects a residual homology of peroxidase loci among Nicotiana species. Some
      species classified in different sections or subgenera but having a common
      geographic center of origin, showed close similarities in peroxidase zymogram.
      Results suggest that these species may be closely related in phylogeny, and/or
      geographic isolation changes the peroxidase genes through mutation and selection.
      Based on leaf peroxidase zymograms of F 1 hybrids, a putative ancestor of N.
      tomentosiformis was the progenitor of N. tabacum at its inception. 

PMID- 24435667
TI  - Cytological studies on some species in genus Pennisetum.
AB  - Detailed microsporogenesis in 4 species of the genus Pennisetum namely P.
      typhoides (n = 7), P. longistylum (n = 18), P. polystachyon (n = 27) and P.
      pedicellatum (n = 27) was studied. Nature of chromosome pairing was critically
      studied and pairing was regular in diploid and allotetraploid species. Some
      multivalents formation occurred in segmental allopolyploids. They displayed
      numerous meiotic irregularities. Aberrant meiosis in the material is evaluated.
      The role of apomixis, hybridization and polyploidy in the evolution of the genus
      is discussed. 

PMID- 24435668
TI  - [Studies on the physiological specialization of Erysiphe graminis DC : IV. The
      host plants of cocksfoot mildew].
AB  - In the described experiments the interaction of 460 grass species with a mildew
      population obtained from Dactylis glomerata L. 'Motterwitzer' was examined. 420
      species remained free of symptoms, while 40 species were susceptible. The most
      susceptible ones were Dactylis aschersoniana Graebner, Dactylis glomerata L.,
      Dactylis glomerata spp. aschersoniana (Graebn.) Thell., and Dactylis polygama
      Horvat, but all showed differences in their behaviour. The unexpectedly low
      susceptibility of Dactylis woronowii Ovcz. should be examined again. Three grass
      species Bouteloua hirsuta Lag., Danthonia provinzialis DC., and Sesleria
      latifolia (Adam) Degen were also highly susceptible to cocksfoot mildew, while on
      wild grasses of the species Agropyron, Bromus, Festuca, Mibora, Poa, and Sesleria
      only few symptoms could be seen. Among cereals only barley could be infected by
      cocksfoot mildew. Not only in the wild form of Dactylis glomerata L. but also in
      the cultivated variety 'Motterwitzer', above 10% were found to be free from
      infection. Therefore the breeding of resistant varieties of Dactylis glomerata L.
      seems to be feasible. 

PMID- 24435669
TI  - Polyphenol content, polyphenoloxidase and peroxidase activity in certain
      Nicotiana species, varieties and interspecific hybrids.
AB  - Eight Nicotiana species including the putative progenitors of N. tabacum,
      Kostoff's amphidiploid (N. sylvestris * N. tomentosiformis), and 19 cultivars
      have been compared for total polyphenols, polyphenoloxidase and peroxidase
      activity in the leaf and/or root by a small plant technique. Greater variations
      for these chemical constituents occurred in the species than in the cultivars. N.
      tomentosiformis was highest in polyphenol content. Root extracts contained more
      polyphenoloxidase than the leaf, but its peroxidase content may not exceed the
      concentration in the leaf. The Kostoff's amphidiploid tended to resemble more the
      low oxidase and polyphenol parent. An additional study based on mature green
      leaves of Burley 21, the progenitor species, and their F 1 hybrids confirmed the
      quantitative differences of these chemical constituents in the species. The
      magnitude of the heterosis appeared to be greater in the hybrids of N.
      tomentosiformis or N. otophora crossed to N. sylvestris than those between the
      Tomentosae members or involving Burley 21 as the parent. An exception was the
      hybrid Burley 21 * N. tomentosiformis which showed heterosis for oxidase
      activities. 

PMID- 24435670
TI  - Analysis of genetic variations in plant type of rice : V. Early vs. sustained
      vigor types in growth and their bearing on yielding potential.
AB  - To examine genetic variation in the growth curve parameters and their
      contribution to factors determining grain yield, 40 randomly chosen F 7 lines of
      a cross between two contrasting rice varieties were measured for dry matter
      weight and for other yielding characters during the growing period. From the dry
      weight data, growth curves were computed using linear and quadratic (Pearl-Reed)
      logistic equations, and various values derived from them were compared among
      lines. The results showed that: 1) The growth curves of the lines varied
      genetically between the "early-vigor" and "sustained-vigor" types. 2) Total
      panicle length per unit area, representing the potentiality for carbohydrates to
      be produced in grains, seemed to depend on the growth rate at floral initiation,
      and panicle weight per unit length, representing the rate of carbohydrate supply
      to the panicles, seemed to depend on the growth rate at heading. These two values
      were negatively correlated. 3) "Early-vigor" types tended to produce more
      panicles but had a low rate of carbohydrate supply than "sustained-vigor" types.
      Either "potentiality" or "supply" was a limiting factor in grain production,
      depending upon the pattern of growth being either "early-vigor" or "sustained
      vigor" type. 

PMID- 24435671
TI  - [Studies on the physiological specialization of Erysiphe graminis DC : V. The
      reaction of important fodder grasses cultivated in the GDR against some races of
      cereal mildew].
AB  - In an examination of the susceptibility of 27 fodder grass varieties cultivated
      in the GDR to 14 races of barley mildew, 9 races of wheat mildew and 1 population
      of rye mildew no infections were obtained. Since the races used represented the
      whole range of pathogenicity of the known races of cereal mildew, it may be
      assumed that under natural conditions cereal mildew does not cause any infection
      in the examined varieties of forage grasses. 

PMID- 24435672
TI  - Hybridization of some Trifolium species through stylar temperature treatments.
AB  - Plants of seven perennial Trifolium species were interspecifically pollinated.
      The female flowers opened at 40  degrees C, and the male flowers opened in the
      greenhouse or field without a temperature treatment. T. pratense was pollinated
      with T. ambiguum, T. hirtum, T. ochroleucum, T. rubens, T. sarosiense, and T.
      medium. T. medium was pollinated with T. pratense. Seeds were obtained from all
      pollinations ; however, 86 of the progeny were morphologically and cytologically
      similar to their female parent, and probably resulted from self-fertilization.
      Many seeds of possible hybrid origin were small and/or did not germinate. Some
      seeds produced weak or albino seedlings which died at an early age. Excised
      pistils of T. medium from flowers that opened at 40  degrees C were more
      compatible with pollen of T. pratense than pistils of T. medium that developed in
      the field, indicating that the elevated temperature caused greater hybrid seed
      production than was observed in our earlier studies. The high temperature
      technique may prove useful in obtaining hybrids in Trifolium. 

PMID- 24435673
TI  - Quantitative genetic analysis in Phalaris and its breeding implications.
AB  - The genetic variation for a number of important agronomic characters within a
      widely based breeding population of Phalaris tuberosa has been analysed, and the
      interrelationships among the variables characterized.Estimates of heritability
      for flowering date, seed retention and seed weight were higher than those for
      cool season growth measured in spaced plants or swards, but all characters showed
      appreciable additive genetic variation, which offers considerable scope for
      further selection. There was no evidence of any general loss of adaptation in the
      widely based population, though flowering date and seed weight tended to show
      increased environmental variability by comparison with the adapted Australian
      cultivar.One of the most important changes in the genetic relationship between
      characters in the breeding population has been the elimination of undesirable
      ecotypic correlations which were present in the parental material prior to
      hybridization and recombination.In the advanced breeding population significant
      intra-population correlations existed between the various estimates of growth
      made on single plants, but in general, estimates of growth made under these
      conditions were not significantly correlated with the performance of the same
      families in swards. Of particular interest, however, were the significant genetic
      correlations between seedling growth of full-sib families measured in controlled
      environments, and the growth of the same families as spaced plants and in
      swards.The predicted response to either direct or indirect selection indicates
      considerable potential for improvement in a number of important characters
      including seedling growth, seed retention, and winter growth in swards. Of
      particular interest is the possibility of increasing sward production as a
      correlated response to intensive selection for seedling growth.A selection
      procedure is described involving simultaneous selection in full-sib families
      grown as swards and spaced plants. This technique provides a useful compromise
      when progress is desired in a number of characters which are best assessed under
      one or the other regime. 

PMID- 24435674
TI  - Within-family selection in Avena fatua and A. barbata.
AB  - Twenty families each of Avena fatua and A. barbata drawn from a natural
      population were used for measuring the response to within-family selection for
      the two extremes in heading date and seed size. The estimates of the relative
      amounts of between- and within-family variation were interpreted in relation to
      the realized responses to show that A. fatua has greater genetic variability than
      A. barbata which, on the other hand, has more phenotypic plasticity. These
      results support our model on the alternative adaptive strategies in the two
      species discussed earlier. 

PMID- 24435675
TI  - On the determination of relative fitness from frequencies of genotypes in
      subsequent generations : Part II. Statistical problems in estimation of
      fitnesses.
AB  - In part I of this paper (Theoret. Appl. Genetics 40, p. 11-17) an algebraic
      treatment of reproduction and selection processes in populations of diploids was
      given. Here the statistical properties of a special fitness estimator, which is
      due to Hayman, are considered. Confidence intervals and tests of significance
      concerning hypotheses about fitnesses are established and checked by computer
      simulation studies in part III. 

PMID- 24435676
TI  - Effects of selection and drift on the dynamics of finite populations : III. Times
      to fixation or loss of an allele in the case of multiple loci and variable
      population size.
AB  - Selection, in the case of a variable finite population size and a two-allelic
      locus with overdominance, caused an acceleration in the time to fixation or loss
      of the favorable allele (i.e. time with selection was less than that with no
      selection) when the deterministic gene frequency equilibrium was above 0.8. The
      acceleration was over a range of initial gene frequencies, dependent on the
      selection intensity and the overdominance parameter.In the case of multiple loci
      and a small, diploid population of fixed size derived from a large population in
      initial linkage equilibrium, an acceleration in the time to fixation or loss
      occurred over a range of initial gene frequencies (as in the one locus case) for
      strong selection intensity (N s>14) and weak overdominance effect. For a large
      number of overdominant loci, acceleration did not occur under linkage. Initial
      coupling or repulsion disequilibrium with independent assortment had no effect on
      the observed acceleration. Repulsion with linkage, however, caused a retardation
      in the time to fixation or loss. 

PMID- 24435678
TI  - [Studies on the relationship of fertility and mode of chromosome pairing in
      tetraploid F1 species hybrids of rye (Secale cereale * Secale montanum)
      heterozygous for three translocated chromosomes].
AB  - 1. The practical purpose of the present investigation was to determine whether
      "preferential pairing" occurs in artificially induced tetraploid F1 species
      hybrids ofS. cereale andS. montanum which are heterozygous for three translocated
      chromosomes. Under these conditions chromosomes might form bivalents rather than
      the multivalent rings and chains usually found, resulting in a normal degree of
      fertility. 2. Several individuals of the tetraploidF 1 generation, heterozygous
      with respect to three translocated chromosomes, showed the expected percentages
      of quadrivalents always found in tetravalent rye, all other chromosome
      associations were bivalent (group 1 in table 1). The remaining individuals
      investigated also produced fewer multivalents than theoretically expected on the
      basis of the model proposed by Linnert (1962) and extended by us to include
      translocation figures composed of three translocated chromosomes. 3. It is to be
      assumed that in all of the plants investigated cytologically the quadrivalents
      were formed by the chromosomes not involved in the translocations. 4. Since the
      fertility of individuals with a strong tendency to form bivalents (group 1 in
      table 1) was no higher than that of plants producing a rather high percentage of
      multivalents, the rather high proportion of bivalents cannot be attributed to
      "preferential pairing" between chromosomes with increasing degrees of homology.
      Instead, it should probably be assumed that in the plants in question chiasma
      frequency was extremely low, so that heteromorphic bivalents instead multivalents
      were produced. 5. Proof of "preferential pairing" by cytological methods alone is
      rather difficult, because of the necessity to correctly distinguish the
      heteromorphic bivalents from the normal ones. It is discussed how use of the
      structural difference of chromosome VI ofS. montanum as compared to chromosome VI
      ofS. cereale which we detected recently, may serve to overcome this difficulty.
      6. It appears that the goal of breeding a perennial, fully fertile, high-yielding
      rye hybrid may be achieved much more easily in diploids than in tetraploids, for
      in the tetraploid species hybrid success depends upon the selection not only of
      genotypes with high heritability for chiasma frequency but also for "zig-zag"
      distribution of the chromosomes involved in the formation of multivalents. In
      spite of our failure, a continued search for true "preferential pairing" may lead
      to its discover. 

PMID- 24435679
TI  - Genetic correlation and response to selection in simulated populations : II.
      Model of complete dominance.
AB  - Effects of truncation selection of a primary trait upon genetic correlation
      between the primary trait and an unselected secondary trait were observed during
      30 generations. Populations were 24 male and 24 female parents per generation
      randomly mated with replacement, the number of offspring set by intensity of
      selection. Each trait was controlled by genes with equal effects and complete
      dominance segregating independently from starting frequencies of 0.5 at each of
      48 loci. Three levels each of genetic correlation, selection, and environmental
      variation were simulated.Genetic correlation decreased faster under more intense
      selection by lower than by upper truncation but behaved similarly in both by
      remaining near initial level when as many as one-half of the offspring were saved
      for parents. Truncation selection decreased genetic correlation in the offspring
      selected to be parents whether selection was by upper or lower truncation.
      Estimates of genetic correlation from covariances between phenotypes of parent
      and offspring were erratic for both directions of selection. 

PMID- 24435677
TI  - Expansion of Foxp3(+) T-cell populations by Candida albicans enhances both Th17
      cell responses and fungal dissemination after intravenous challenge.
AB  - Candida albicans remains the fungus most frequently associated with nosocomial
      bloodstream infection. In disseminated candidiasis, the role of Foxp3(+)
      regulatory T (Treg) cells remains largely unexplored. Our aims were to
      characterize Foxp3(+) Treg-cell activation in a murine intravenous challenge
      model of disseminated C. albicans infection, and determine the contribution to
      disease. Flow cytometric analyses demonstrated that C. albicans infection drove
      in vivo expansion of a splenic CD4(+) Foxp3(+) population that correlated
      positively with fungal burden. Depletion from Foxp3(hCD2) reporter mice in vivo
      confirmed that Foxp3(+) cells exacerbated fungal burden and inflammatory renal
      disease. The CD4(+) Foxp3(+) population expanded further after in vitro
      stimulation with C. albicans antigens (Ags), and included at least three cell
      types. These arose from proliferation of the natural Treg-cell subset, together
      with conversion of Foxp3(-) cells to the induced Treg-cell form, and to a cell
      type sharing effector Th17-cell characteristics, expressing ROR-gammat, and
      secreting IL-17A. The expanded Foxp3(+) T cells inhibited Th1 and Th2 responses,
      but enhanced Th17-cell responses to C. albicans Ags in vitro, and in vivo
      depletion confirmed their ability to enhance the Th17-cell response. These data
      lead to a model for disseminated candidiasis whereby expansion of Foxp3(+) T
      cells promotes Th17-cell responses that drive pathology. 

PMID- 24435680
TI  - [Plastome dependent pollen sterility inOenothera].
AB  - Pollen in which the genome complexesflavens (derived fromOe. suaveolens)
      orgaudens (derived fromOe. lamarckiana) are combined withparviflora plastids
      (plastome IV) fails to germinate even though it is well developed otherwise. This
      inability to germinate, however, is not always complete. Those exceptional pollen
      grains which do germinate do not get this ability by a change of their genome.
      The germination rate varies modificatively. Furthermore it has clearly been
      demonstrated that the degree of sterility is influenced by the genotype of the
      sporophyte. But this influence of the diploid sporophyte on the haploid
      gametophyte does not go as far as to completely suspend differences in
      germination behaviour of pollen with plastome IV on the one hand and of (normal)
      pollen with other plastome types on the other hand. 

PMID- 24435681
TI  - Combining ability and inheritance of pod and cluster number inPhaseolus mungo L.
AB  - A set of sixPhaseolus mungo lines was studied in a diallel cross over two
      generations to investigate general and specific combining ability and mode of
      inheritance for cluster and pod number. General combining ability effects were
      more important for both characters.Per se performance appeared to be a good index
      to rank the parental lines for general combining ability. Additive gene effects
      with partial dominance to overdominance for these traits were noted. High cluster
      and pod number seem to be governed by recessive genes. 

PMID- 24435682
TI  - [Interactions between a turnip-mosaic virus and the genotype of the host].
AB  - InMatthiola incana R. Br. the phenomenon of so called "breaking of flower color"
      is observed which is manifested in white areas dilution or intensification of the
      normally pink or violet flower colors. This phenomenon is shown to be caused by a
      virus of the turnip-mosaic-type. There is an interaction between the virus and
      the genotype of the host, in which are involved only genes controlling the
      quantity of the anthocyanin pigments but not genes responsible for alteration of
      the molecule structure of the anthocyanins. 

PMID- 24435683
TI  - Function ofY chromosomes inRumex thyrsijlorus.
AB  - 1. Numerous polyploid and diploid plants ofR. thyrsiflorus with various numbers
      ofX andY chromoso mes were obtained. Analysis of these plants confirmed earlier
      conclusions (Zuk, 1963) thatY chromosomes carry no sex-determining genes. 2.
      Investigation of pollen fertility of male plants withoutY chromosomes, and with
      one or moreY chromosomes, seems to indicate that in theY chromosomes ofR.
      thyrsiflorus are located some factors reponsible for the fertility of male
      plants. This result is supported by cytological data (Zuk, 1969) indicating thatY
      chromosomes ofR. thyrsiflorus are active in premeiotic stages of
      microsporogenesis. Meiosis in plants withoutY chromosomes and with oneY
      chromosome was also studied. In all cases conjugation of chromosomes and meiotic
      divisions in PMC were normal. These data suggest that there are no genes located
      inY chromosomes responsible for synapsis or the course of meiotic division in PMC
      ofR. thyrsiflorus. 3. In a natural population ofR. thyrsiflorus the male
      individuals are less numerous than the female ones. This is due to nonrandom
      fertilization. The gametesYY + 6A = 8 fertilize less frequently than do gametesX
      + 6 A = 7. In crosses involving a male plant with chromosome constitutionXYYYY +
      12A = 17, which produces more uniform gametes as regardsY chromosomes, there were
      more male individuals than normally. This is interpreted as evidence that the
      preponderance of females inR. thyrsiflorus is connected withY chromosomes. 

PMID- 24435684
TI  - [Not Available].
AB  - In clonus and progenies linear phenotypic and genotypic correlations and
      interactions between genotypes, years and locations as well as methods for the
      estimation of the heritability are investigated.The significant correlation
      coefficients found should facilitate selection for more than one character at one
      time. With one exception high genotypic correlations correspond to significant
      phenotypic ones (Table 1). Usually genotype/year and genotype/year/location
      interactions were not significant, but genotype/location-interactions were
      regularly significant in trials carried over more than one season. There were
      also clear differences in the ability of genotypes to yield consistently in
      different locations over several seasons ("ecovalence").Estimates of
      heritabilities both in the narrow sense and in the broad sense were relatively
      high, especially those of flowering date, plant height and leaf number. Both
      types of heritabilities showed the same ranking (Table 3). Half-sib families from
      polycrosses were not suitable for half-sib correlations.From the results obtained
      it has been concluded that one year trials with replicated clones in different
      locations yield useful estimates of heritability. Therefore, in breeding plants
      with long generation times, raising of progenies may be dispensed with in the
      interest of saving time. 

PMID- 24435685
TI  - Chromosome behavior in a hypertriploid plant of ryegrass.
AB  - A hypertriploid (2n = 22) was detected in the progeny of a desynaptic diploid (2n
      = 14) plant of perennial ryegrass,Lolium perenne L. The hypertriploid did not
      differ in morphology from its maternal-sib diploids, but showed larger stomata
      and pollen. The microsporocytes showed a mean chromosome association of 4.3 I +
      3.4 II + 3.2 III + 0.3 IV at metaphase I with a mean chiasma number of 14.4 per
      cell. The 33 types of observed chromosome configurations could be explained by
      assuming that the plant was trisomie for 6 chromosomes and tetrasomic for one
      chromosome. Karyotype analysis confirmed the above assumption and revealed
      tetrasomy of chromosome number VI. However, two chromosome associations, 1I + 4
      II + 3 III + IIV and 2 I + 5 II + 2 III + 1 IV suggested the presence of
      displaced duplications within the genome of ryegrass. The tetrasomic chromosome
      formed mostly a quadrivalent, which often broke down to form 2 II or 1 I + 1 III
      and rarely 2 I + 1 II or 4 univalents. Most of the univalents arose from the
      trisomic chromosomes and divided precociously at anaphase 1, producing diads and
      tetrads with unequal chromosome numbers. The plant was highly sterile and set no
      seed on controlled crossing. 

PMID- 24435686
TI  - Leucosporidium escuderoi f.a., sp. nov., a basidiomycetous yeast associated with
      an Antarctic marine sponge.
AB  - A basidiomycetous yeast, strain E2A-C3-II, was isolated from a marine sponge
      (Hymeniacidon sp.) collected at a depth of 6 m in Fildes Bay, King George Island,
      Antarctica. The phylogenetic analysis revealed that the yeast isolated is related
      to Leucosporidium drummii, Leucosporidiella muscorum and to the Leucosporidium
      scottii group, including Leucosporidiella creatinivora and Leucosporidiella
      yakutica. The analysis of the nucleotide differences and the genetic distances of
      the D1/D2 domain of the LSU rDNA gene and 5.8S ITS regions support that strain
      E2A-C3-II represents a new species. The novel species can be distinguished from
      L. drummii by its ability to assimilate L-sorbose, L-rhamnose, lactose and
      ribitol. The maximum temperature for growth was 25  degrees C. On the basis of
      morphological, biochemical and physiological characterization, and phylogenetic
      and nucleotide analysis, a novel basidiomycetous yeast species, Leucosporidium
      escuderoi f.a., sp. nov., is proposed. The type strain is E2A-C3-II(T) (=CBS
      12734(T) =CECT 13080(T)). The Mycobank ( http://www.mycobank.org ) accession
      number is MB 804654. The nucleotide sequences of D1/D2 domain of the LSU rDNA
      gene and 5.8S-ITS regions obtained in this work have been deposited in Genbank
      under the Accession numbers JN181009 and JN197600, respectively.

PMID- 24435687
TI  - Photosynthesis of cotton plants exposed to elevated levels of carbon dioxide in
      the field.
AB  - The cotton (Gossypium hirsutum L.) plant responds to a doubling of atmospheric
      CO2 with almost doubled yield. Gas exchange of leaves was monitored to discover
      the photosynthetic basis of this large response. Plants were grown in the field
      in open-top chambers with ambient (nominally 350 MUl/l) or enriched (nominally
      either 500 or 650 MUl/l) concentrations of atmospheric CO2. During most of the
      season, in fully-irrigated plants the relationship between assimilation (A) and
      intercellular CO2 concentration (ci) was almost linear over an extremely wide
      range of ci. CO2 enrichment did not alter this relationship or diminish
      photosynthetic capacity (despite accumulation of starch to very high levels)
      until very late in the season, when temperature was somewhat lower than at
      midseason. Stomatal conductance at midseason was very high and insensitive to
      CO2, leading to estimates of ci above 85% of atmospheric CO2 concentration in
      both ambient and enriched chambers. Water stress caused A to show a saturation
      response with respect to ci, and it increased stomatal closure in response to CO2
      enrichment. In fully-irrigated plants CO2 enrichment to 650 MUl/l increased A
      more than 70%, but in water-stressed plants enrichment increased A only about
      52%. The non-saturating response of A to ci, the failure of CO2 enrichment to
      decrease photosynthetic capacity for most of the season, and the ability of the
      leaves to maintain very high ci, form in part the basis for the very large
      response to CO2 enrichment. 

PMID- 24435688
TI  - Formation of the S2 state and structure of the Mn complex in photosystem II
      lacking the extrinsic 33 kilodalton polypeptide.
AB  - Electron paramagnetic resonance (EPR) spectroscopy and O2 evolution assays were
      performed on photosystem II (PSII) membranes which had been treated with 1 M
      CaCl2 to release the 17, 23 and 33 kilodalton (kDa) extrinsic polypeptides.
      Manganese was not released from PSII membranes by this treatment as long as a
      high concentration of chloride was maintained. We have quantitated the EPR
      signals of the several electron donors and acceptors of PSII that are
      photooxidized or reduced in a single stable charge separation over the
      temperature range of 77 to 240 K. The behavior of the samples was qualitatively
      similar to that observed in samples depleted of only the 17 and 23 kDa
      polypeptides (de Paula et al. (1986) Biochemistry25, 6487-6494). In both cases,
      the S2 state multiline EPR signal was observed in high yield and its formation
      required bound Ca(2+). The lineshape of the S2 state multiline EPR signal and the
      magnetic properties of the manganese site were virtually identical to those of
      untreated PSII membranes. These results suggest that the structure of the
      manganese site is unaffected by removal of the 33 kDa polypeptide. Nevertheless,
      in samples lacking the 33 kDa polypeptide a stable charge separation could only
      be produced in about one half of the reaction centers below 160 K, in contrast to
      the result obtained in untreated or 17 and 23 kDa polypeptide-depleted PSII
      membranes. This suggests that one function of the 33 kDa polypeptide is to
      stabilize conformations of PSII that are active in secondary electron transfer
      events. 

PMID- 24435689
TI  - C3-C 4 intermediate photosynthetic characteristics of cassava (Manihot esculenta
      Crantz) : I. Gas exchange.
AB  - The gas exchange characteristics of cassava were compared with one C3 species,
      common bean, and two C4 species, maize and amaranthus. Cassava leaf
      photorespiration, about 12% of maximum net photosynthesis in normal air, and the
      CO2 release in CO2-free air under intense light were lower than the values
      typically reported for C3 species. The CO2 compensation point of whole leaves (25
      cm(3) CO2m(-3)) was intermediate between C3 and C4 species values.Gas exchange
      was restricted to either the upper or lower surface of amphistomatous leaves by
      covering one side of the leaf with silicone grease. The CO2 compensation point of
      the upper leaf surface was less than 6 cm(3) CO2m(-3) and the CO2 release into
      CO2-free air in the light was essentially zero. On the lower leaf surface
      considerable CO2 release occurred in both the light and the dark.The hypothesis
      presented to explain these results is the existence of an efficient CO2 recycling
      mechanism in the palisade layer in the upper half of the leaf. In the light of
      recent data (presented in the second paper of this series) indicating that
      cassava produces C4 acids as primary products of photosynthesis, it is proposed
      that this hypothesis is consistent with the possible existence of the C4
      photosynthetic pathway in the palisade layer of cassava leaves.The results and
      hypothesis are discussed in relation to the crop's adaptation to the
      environmental conditions where it is normally grown. The implications of
      variation in anatomical features such as stomatal distribution on both surfaces
      of the leaf are analyzed with a view to enhancing the potential productivity of
      cassava under stress conditions. 

PMID- 24435690
TI  - C3-C 4 intermediate photosynthetic characteristics of cassava (Manihot esculenta
      Crantz) : II. Initial products of(14)CO 2 fixation.
AB  - Cassava, bean and maize leaves were fed with(14)CO2 in light and the primary
      products of photosynthesis identified 5 and 10 seconds after assimilation. In
      maize, approximately three quarters of the labelled carbon was incorporated in C4
      acids, in beans about two thirds in PGA, and in cassava approximately 40-60% in
      C4 acids with 30-50% in PGA. These data indicate that cassava possesses the C4
      photosynthetic cycle, however due to the lack of typical Kranz anatomy
      appreciable carbon assimilation takes place directly through the Calvin-Benson
      Bassham cycle. 

PMID- 24435691
TI  - Phosphorylation of thylakoid proteins during chloroplast biogenesis in greening
      etiolated and light-grown wheat leaves.
AB  - Phosphorylation of polypeptides in isolated thylakoids was examined during
      chloroplast biogenesis in greening etiolated wheat leaves and 4 day-old wheat
      leaves grown under a diurnal light regime. At early stages of plastid development
      standard thylakoid preparations were heavily contaminated with nuclear proteins,
      which distorted the polypeptide phosphorylation profiles. Removal of
      contamination from membranes by sucrose density centrifugation demonstrated that
      the major membrane phosphoprotein in etioplasts was at 35 kDa. During etioplast
      greening a number of phosphoproteins appeared, of which the 25-27 kDa apoproteins
      of the light-harvesting chlorophylla/b protein complex associated with
      photosystem II (LHCII) became the most dominant. At the early stages of thylakoid
      development found at the base of the 4-day-old light grown leaf the LHCII
      apoproteins were evident as phosphoproteins; however the major phosphoprotein was
      polypeptide atca. 9kDA. Phosphorylation of both the LHCII apoproteins and the 9
      kDa polypeptide in these thylakoids was not light-dependent. In the older
      thylakoids isolated from the leaf tip the LHCII apoproteins were the major
      phosphoproteins and their phosphorylation had become light-regulated; however
      phosphorylation of the 9 kDa polypeptide remained insensitive to light. 

PMID- 24435692
TI  - Changes in spinach thylakoid activity due to nitrite ions.
AB  - The introduction of nitrite ions into the bathing medium of broken spinach
      chloroplasts causes changes in the properties of these organelles which depend on
      the concentration of nitrite and the time of exposure. In the presence of 1 mM
      nitrite, there is an inhibition of the rate of oxygen evolution and an increase
      in fluorescence emission which suggests a site for nitrite inhibition between the
      two photosystems. When 5 mM nitrite is present for times longer than 10 minutes,
      there is a decrease in the PS2 partial reaction rate as indicated by the oxygen
      burst, an increase in the PS1 partial reaction rate, a decrease in fluorescence
      emission and an increase in the fluorescence emitted at 729 nm compared with that
      at 693 nm observed at - 176 degrees C. These changes are consistent with an
      increase in the proportion of absorbed light energy reaching PS1 caused by
      prolonged exposure to a sufficient concentration of nitrite ions in the light. 

PMID- 24435693
TI  - The effect of ammonium and nitrate on CO2 assimilation, RuBP and PEP carboxylase
      activity and dry matter production in wheat.
AB  - Photosynthetic(14)CO2 assimilation, ribulose 1, 5-bisphosphate carboxylase
      (RuBPC), phosphoenol pyruvate carboxylase (PEPC) and dry matter (DM) production
      were examined in wheat under varying levels and forms of nitrogen.(14)CO2
      assimilation increased gradually after germination reaching a peak value at
      anthesis, followed by a sharp decline. A similar pattern was observed for both
      the carboxylases, RuBPC and PEPC activities. Increase in nitrogen levels, in
      general, brought about a significant increase over the control (zero-nitrogen)
      in(14)CO2 assimilation, RuBPC, PEPC activities and DM production. There were no
      significant differences in RuBPC activity and(14)CO2 assimilation with respect to
      the forms of nitrogen. Significantly higher PEPC activity and DM was observed in
      plants supplied with nitrate-nitrogen (NO3-N), as compared to those supplied with
      ammonium-nitrogen (NH4-N). The significance of PEPC activity in C3 photosynthesis
      is discussed in relation to DM distribution. 

PMID- 24435694
TI  - Purification of membrane-bound ferredoxin: NADP(+) oxidoreductase and of
      plastocyanin from a detergent extract of washed thylakoids.
AB  - A method is described for the isolation and purification of ferredoxin-NADP(+)
      oxidoreductase (FNR, E.C. 1.18.1.2) and plastocyanin from spinach thylakoids. FNR
      is recovered from pools which are loosely and tightly bound to the membrane, with
      minimal disruption of pigment-protein complexes; yields can thus be higher than
      from procedures which extract only the loosely bound enzyme.Washed thylakoid
      membranes were incubated with the dipolar ionic detergent CHAPS (3-(3
      cholamidopropyl-dimethylammonio)-1-propane-sulfonate). This provided an extract
      containing FNR and PC as its principal protein components, which could be rapidly
      separated from one another by chromatography on an anion-exchange column. FNR was
      purified to homogeneity (as judged from sodium dodecyl sulfate gel
      electrophoresis and the ratio between protein and flavin absorption maxima),
      using chromatography on phosphocellulose followed by batchwise adsorption to, and
      elution from hydroxylapatite. Plastocyanin was further purified on a Sephadex G
      75 molecular sieve column.A typical yield, obtained in 3-4 days from 1 kg of
      deveined spinach leaves, was 7 mg of pure FNR (a single protein of Mr=37,000) and
      3.5 mg of plastocyanin. 

PMID- 24435696
TI  - Development of a preference-based index from the National Eye Institute Visual
      Function Questionnaire-25.
AB  - IMPORTANCE: Understanding how individuals value health states is central to
      patient-centered care and to health policy decision making. Generic preference
      based measures of health may not effectively capture the impact of ocular
      diseases. Recently, 6 items from the National Eye Institute Visual Function
      Questionnaire-25 were used to develop the Visual Function Questionnaire-Utility
      Index health state classification, which defines visual function health states.
      OBJECTIVE: To describe elicitation of preferences for health states generated
      from the Visual Function Questionnaire-Utility Index health state classification
      and development of an algorithm to estimate health preference scores for any
      health state. DESIGN, SETTING, AND PARTICIPANTS: Nonintervention, cross-sectional
      study of the general community in 4 countries (Australia, Canada, United Kingdom,
      and United States). A total of 607 adult participants were recruited from local
      newspaper advertisements. In the United Kingdom, an existing database of
      participants from previous studies was used for recruitment. INTERVENTIONS: Eight
      of 15,625 possible health states from the Visual Function Questionnaire-Utility
      Index were valued using time trade-off technique. MAIN OUTCOMES AND MEASURES: A
      theta severity score was calculated for Visual Function Questionnaire-Utility
      Index-defined health states using item response theory analysis. Regression
      models were then used to develop an algorithm to assign health state preference
      values for all potential health states defined by the Visual Function
      Questionnaire-Utility Index. RESULTS: Health state preference values for the 8
      states ranged from a mean (SD) of 0.343 (0.395) to 0.956 (0.124). As expected,
      preference values declined with worsening visual function. Results indicate that
      the Visual Function Questionnaire-Utility Index describes states that
      participants view as spanning most of the continuum from full health to dead.
      CONCLUSIONS AND RELEVANCE: Visual Function Questionnaire-Utility Index health
      state classification produces health preference scores that can be estimated in
      vision-related studies that include the National Eye Institute Visual Function
      Questionnaire-25. These preference scores may be of value for estimating
      utilities in economic and health policy analyses.

PMID- 24435697
TI  - Next Generation sequencing is the impetus for the next generation of laboratory
      based genetic counselors.
AB  - Next generation sequencing (NGS) is dramatically increasing the number of
      clinically available genetic tests and thus the number of patients in which such
      testing may be indicated. The complex nature and volume of the reported results
      requires professional interpretation of the testing in order to translate and
      synthesize the meaning and potential benefit to patients, and genetic counselors
      are uniquely suited to provide this service. The increased need for genetic
      counselors in this role, coupled with the time required and a limited number of
      trained and available counselors presents a challenge to current models for
      making genetic testing available to patients and their healthcare providers
      effectively and efficiently. The employment of genetic counselors at
      genetic/genomic laboratories is one model to expand the resources for providing
      this service. In this article, we briefly review the advent of NGS and its
      clinical applications, examine the core skills of genetic counselors and
      delineate the expanding roles and responsibilities of laboratory-based genetic
      counselors. We also propose changes to the genetic counseling training program
      curriculum to account for the increasing opportunities for genetic counselors to
      contribute and thrive within genetic testing laboratories. 

PMID- 24435698
TI  - Ethics in psychiatric research : resources for faculty development and resident
      education.
AB  - Controversy has arisen in recent years about the participation of psychiatric
      patients in questionably ethical research protocols. Consequently, academic
      psychiatrists have been called upon to enrich their understanding of the ethical
      aspects of research and to teach residents more intensively about these issues in
      scientific methodology. Toward these ends, the authors have assembled an
      extensive resource listing in the area of psychiatric research ethics. Articles
      were identified through MEDLINE and BIOETHICS LINE computerized searches and the
      authors' review of relevant literature through 1996. Emphasis was placed on those
      pieces with special historical value, empirical studies, and papers that provide
      background on the current controversies in psychiatric research ethics. The
      references were organized into five logical categories. Based on the resource
      review, the authors briefly discuss areas related to research ethics that merit
      greater attention in academic psychiatry. 

PMID- 24435699
TI  - Pediatric residents' experiences with suicidal patients : implications for
      training.
AB  - The increased prevalence of attempted and completed suicide in childhood and
      adolescence, combined with recent emphasis on secondary prevention by primary
      care physicians, underscores the need for effective training of pediatricians and
      other primary care providers in assessment of suicidal risk. It is probable that
      psychiatrists will play a leading role in this training. This descriptive study
      uses interview data from a unique cohort of 19 graduating pediatric residents
      from 2 programs to document qualitative and quantitative aspects of their
      clinical experience with suicidal children and adolescents. The implications of
      these findings for those involved in resident training are discussed in light of
      pertinent literature. 

PMID- 24435700
TI  - Religious training and religiosity in psychiatry residency programs.
AB  - The authors present the results of a survey that inquired into the religious life
      of 121 residents from 5 psychiatric residency programs. In addition, the study
      sought to explore the didactic and supervision experience of the residents
      regarding religious issues. The authors' results show that this group of
      residents appears to be more religious than what has been reported before in
      prior studies of psychiatrists' religious beliefs. While didactic exposure was
      limited, those who received didactic exposure were more likely than those who did
      not to believe that religion is important in the clinical setting, and the former
      also felt more competent to recognize and attend to a patient's religious and
      spiritual issues. Still, most residents felt competent to address religious
      issues in their clinical encounter. The implications of the results are discussed
      as they relate to training. 

PMID- 24435701
TI  - Teaching managed care : philosophy and technique.
AB  - The authors describe a case-oriented seminar on managed care designed to teach
      psychiatric residents and medical students the principles of cost containment and
      delivery of quality care. The participants engage in role-play (reviewer,
      provider, appeal arbitrator) to elucidate the process. The response of the
      participants indicates that this seminar is a useful teaching model. Salient
      points regarding the content and process of the seminar are discussed in some
      detail. 

PMID- 24435702
TI  - Literature as an introduction to psychiatric ethics.
AB  - Responding to requests for an earlier introduction to psychiatric ethics, the
      authors added "An Introduction to Psychiatric Ethics Through Literature" seminar
      to their institution's first-year curriculum. The authors' primary objective was
      to increase the sensitivity of beginning psychiatric residents to ethical
      dilemmas. The 11-session seminar was co-led by a psychiatrist and a literary
      scholar. At each session, the group discussed a short story selected by the
      seminar leaders, with the discussion centering on ethical considerations raised
      by the story and their relevance to the practice of psychiatry. The residents
      gave the seminar high ratings for its increasing their ethical sensitivity and
      the stimulating content of the stories. 

PMID- 24435703
TI  - Mentoring psychiatric trainees' first paper for publication.
AB  - The authors describe their experience supervising and collaborating on projects
      that led to the first publications of several medical students and psychiatric
      residents. Rather than mandating a research project of all the residents, the
      faculty focus effort on the trainees with a sincere interest in writing a
      scholarly paper for publication. The authors break down the procedure of
      developing a published project into manageable steps that reflect and teach the
      scientific process. The mentoring required for these trainee-faculty publications
      is involved and time consuming, but the process is extremely rewarding. Four
      successful projects illustrate different levels of publication possibilities for
      trainees and demonstrate the positive effects the experiences had on their
      academic aspirations. 

PMID- 24435705
TI  - The world wide web and internet: on-line communication, collaboration, and
      collegiality.

PMID- 24435707
TI  - A ROS/STAT3/HIF-1alpha signaling cascade mediates EGF-induced TWIST1 expression
      and prostate cancer cell invasion.
AB  - BACKGROUND: Epidermal growth factor (EGF) has been known to induce epithelial
      mesenchymal transition (EMT) and prostate cancer cell progression. However, a
      detailed underlying mechanism by which EGF induces EMT and prostate cancer cell
      progression remained to be answered. Hypoxia-inducible factor (HIF)-1alpha and
      TWIST1 are transcription factors implicated in EMT and cancer metastasis. The
      purpose of this study is to determine the underlying mechanism of EGF-induced
      TWIST1 expression and prostate cancer invasion. METHODS: siRNAs were used to
      silence genes. Immunoblotting, quantitative RT-PCR and immunofluorescence
      analysis were used to examine protein or mRNA expression. Modified Boyden chamber
      and invasion assay kit with Matrigel-coated inserts were used to determine
      prostate cancer cell migration and invasion, respectively. RESULTS: We observed
      that EGF induced HIF-1alpha expression and morphological change of prostate
      cancer epithelial cells to mesenchymal cells. Silencing HIF-1alpha expression
      dramatically reduced EGF-induced TWIST1 expression and prostate cancer cell EMT.
      Conversely, transfection of the cells with HIF-1alpha siRNA reversed the reduced
      E-cadherin expression by EGF. Pretreatment of the cells with pharmacological
      inhibitors of reactive oxygen species [ROS, N-acetylcysteine (NAC)] and STAT3
      (WP1066) but not p38 MAPK (SB203580) significantly reduced EGF-induced HIF-1alpha
      mRNA and protein expression. Further, pretreatment of the cells with NAC
      attenuated EGF-induced STAT3 phosphorylation. In addition, we showed that TWIST1
      mediated EGF-induced N-cadherin expression, leading to prostate cancer invasion.
      CONCLUSIONS: We demonstrate a mechanism by which EGF promotes prostate cancer
      cell progression through a ROS/STAT3/HIF-1alpha/TWIST1/N-cadherin signaling
      cascade, providing novel biomarkers and promising therapeutic targets for
      prostate cancer cell progression.

PMID- 24435708
TI  - Increased spring freezing vulnerability for alpine shrubs under early snowmelt.
AB  - Alpine dwarf shrub communities are phenologically linked with snowmelt timing, so
      early spring exposure may increase risk of freezing damage during early
      development, and consequently reduce seasonal growth. We examined whether
      environmental factors (duration of snow cover, elevation) influenced size and the
      vulnerability of shrubs to spring freezing along elevational gradients and snow
      microhabitats by modelling the past frequency of spring freezing events. We
      sampled biomass and measured the size of Salix herbacea, Vaccinium myrtillus,
      Vaccinium uliginosum and Loiseleuria procumbens in late spring. Leaves were
      exposed to freezing temperatures to determine the temperature at which 50% of
      specimens are killed for each species and sampling site. By linking site snowmelt
      and temperatures to long-term climate measurements, we extrapolated the frequency
      of spring freezing events at each elevation, snow microhabitat and per species
      over 37 years. Snowmelt timing was significantly driven by microhabitat effects,
      but was independent of elevation. Shrub growth was neither enhanced nor reduced
      by earlier snowmelt, but decreased with elevation. Freezing resistance was
      strongly species dependent, and did not differ along the elevation or snowmelt
      gradient. Microclimate extrapolation suggested that potentially lethal freezing
      events (in May and June) occurred for three of the four species examined.
      Freezing events never occurred on late snow beds, and increased in frequency with
      earlier snowmelt and higher elevation. Extrapolated freezing events showed a
      slight, non-significant increase over the 37-year record. We suggest that earlier
      snowmelt does not enhance growth in four dominant alpine shrubs, but increases
      the risk of lethal spring freezing exposure for less freezing-resistant species.

PMID- 24435709
TI  - SIRT1 knockdown promotes neural differentiation and attenuates the heat shock
      response.
AB  - Neurons have a limited capacity for heat shock protein (HSP) induction and are
      vulnerable to the pathogenic consequence of protein misfolding and aggregation as
      seen in age-related neurodegenerative diseases. Sirtuin 1 (SIRT1), an NAD(+) 
      dependent lysine deacetylase with important biological functions, has been shown
      to sustain the DNA-binding state of HSF1 for HSP induction. Here we show that
      differentiation and maturation of embryonic cortical neurons and N2a
      neuroprogenitor cells is associated with decreases in SIRT1 expression and heat
      shock-dependent induction of HSP70 protein. Tests of a pharmacological activator
      and an inhibitor of SIRT1 affirm the regulatory role of SIRT1 in HSP70 induction.
      Protein cross-linking studies show that nuclear SIRT1 and HSF1 form a co
      migrating high molecular weight complex upon stress. The use of retroviral
      vectors to manipulate SIRT1 expression in N2a cells show that shRNA-mediated
      knock down of SIRT1 causes spontaneous neurite outgrowth coincident with reduced
      growth rate and decreased induction of hsp70-reporter gene, whereas SIRT1 over
      expression blocks the induced neural differentiation of N2a cells. Our results
      suggest that decreased SIRT1 expression is conducive to neuronal differentiation
      and this decrease contributes to the attenuated induction of HSPs in neurons.

PMID- 24435710
TI  - The order effect of combined endurance and strength loadings on force and hormone
      responses: effects of prolonged training.
AB  - PURPOSE: To examine acute responses and recovery of force and serum hormones to
      combined endurance and strength loadings utilizing different orders of exercises
      before and after training. METHODS: Physically active men were matched to an
      order sequence of endurance followed by strength (E + S, n = 12) or strength
      followed by endurance (S + E, n = 17). The subjects performed one experimental
      loading consisting of steady-state cycling and a leg press protocol before and
      after 24 weeks of order-specific combined training. RESULTS: No between-group
      difference in acute reductions of force was observed at week 0 (E + S -23 %, p <
      0.001; S + E -22 %, p < 0.01) and 24 (E + S -25 %, p < 0.001; S + E -27 %, p <
      0.001) and recovery in force was completed after 24 h in both groups at week 0
      and 24. Concentrations of growth hormone (22-kDa) increased post-acute loading at
      week 0 (E + S, +57 fold, p < 0.05; S + E, +300 fold, p < 0.001; between-groups p
      < 0.001) and 24 (E + S, +80 fold, p < 0.01; S + E, +340 fold, p < 0.05; between
      groups p < 0.05). No significant acute responses in concentrations of
      testosterone were observed at week 0 or 24. However, at week 0 testosterone was
      reduced during recovery following the E + S loading only (24 h -23 %, p < 0.01;
      48 h -21 %, p < 0.001; between-groups at 24 and 48 h, p < 0.05), but was no
      longer observed after training. 1RM strength improved similarly in E + S (13 %, p
      < 0.001) and S + E (17 %, p < 0.001). CONCLUSIONS: This study showed an order
      effect (E + S vs. S + E) in concentrations of testosterone during 2 days of
      recovery at week 0, which was diminished after 24 weeks of training. The initial
      difference in testosterone concentrations during recovery did not seem to be
      associated with strength development.

PMID- 24435713
TI  - Stem cell therapy in ALS: possible benefit?

PMID- 24435712
TI  - Thermal influence of radiofrequency ablation for bone: an experimental study in
      normal rabbit bone.
AB  - OBJECTIVE: To evaluate the heat effects of radiofrequency ablation (RFA) on
      normal bone by mechanical testing, MRI, and histology. MATERIALS AND METHODS: The
      institutional animal care and use committee approved the animal study. Thirty-two
      adult Japanese white rabbits were included in our study. Bone biopsy needles were
      inserted from the distal end of the right (RFA side) and the left (control side)
      femurs using a fluoroscopic guide. A 17-gauge internally cooled RFA electrode
      with a 2-cm active tip was inserted through the needle to the right femur, and
      RFA was performed for 12 min using a 200-W generator. Animals were divided into
      four groups and 8 animals from each group were euthanized on day 1, day 7, day
      30, and day 60 after RFA. MRI was performed prior to euthanasia. Three-point
      bending test was performed to measure flexural strength. Student's t test was
      used to evaluate for significant differences between RFA and control side for
      each group. Femurs underwent histological examination by hematoxylin and eosin
      staining after the bending test. RESULTS: MRI showed a high-intensity rim around
      the bone on T2WI. Three-point bending test showed no statistically significant
      differences (P < 0.05) between the RFA and the control side in any of the groups.
      Histologically, osteocytes of cortical bone showed cell death, but the lamellar
      structure was preserved in all groups and bone remodeling was observed.
      CONCLUSION: Heat by RFA did not change normal bone strength within 2 months,
      despite the heat effects in the cortical bone and cell death.

PMID- 24435711
TI  - Peering through the glare: using dual-energy CT to overcome the problem of metal
      artefacts in bone radiology.
AB  - OBJECTIVE: Imaging of patients with large metal implants remains one of the most
      difficult endeavours for radiologists. This article reviews the theory of dual
      energy CT (DECT) and its ability to reduce metal artefact, thus enhancing the
      diagnostic value of musculoskeletal imaging. The strengths, weaknesses, and
      alternative applications of DECT, as well as areas requiring further research,
      will also be reviewed. CONCLUSION: Currently, DECT stands as the frontier for
      metal artefact reduction in musculoskeletal imaging. DECT requires no additional
      radiation and provides significantly enhanced image acquisition. When considered
      along with its other capabilities, DECT is a promising new tool for
      musculoskeletal and trauma radiologists.

PMID- 24435714
TI  - Frank H. Netter MD and a brief history of medical illustration.

PMID- 24435715
TI  - Results of clubfoot management using the Ponseti method: do the details matter? A
      systematic review.
AB  - BACKGROUND: Although the Ponseti method is accepted as the best choice for
      treatment of clubfoot, the treatment protocol is labor intensive and requires
      strict attention to details. Deviations in strict use of this method are likely
      responsible for the variations among centers in reported success rates.
      QUESTIONS/PURPOSES: We wished to determine (1) to what degree the Ponseti method
      was followed in terms of manipulation, casting, and percutaneous Achilles
      tenotomy, (2) whether there was variation in the bracing type and protocol used
      for relapse prevention, and (3) if the same criteria were used to diagnose and
      manage clubfoot relapse. METHODS: We conducted a systematic review of MEDLINE,
      EMBASE(TM), and the Cochrane Library. Studies were summarized according to the
      Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement.
      Five hundred ninety-one records were identified with 409 remaining after
      deduplication, in which 278 irrelevant studies and 22 review articles were
      excluded. Of the remaining 109 papers, 19 met our inclusion criteria. All 19
      articles were therapeutic studies of the Ponseti method. RESULTS: The details of
      manipulation, casting, or percutaneous Achilles tenotomy of the Ponseti method
      were poorly described in 11 studies, whereas the main principles were not
      followed in three studies. In three studies, the brace type deviated
      significantly from that recommended, whereas in another three studies the bracing
      protocol in terms of hours of recommended use was not followed. Furthermore no
      unified criteria were used for judgment of compliance with brace use. The
      indication for recognition and management of relapse varied among studies and was
      different from the original description of the Ponseti method. CONCLUSIONS: We
      found that the observed clinically important variation may have been the result
      of deviations from the details regarding manipulation, casting, percutaneous
      Achilles tenotomy, use of the bar-connected brace, and indication for relapse
      recognition and management recommended for the classic Ponseti approach to
      clubfoot management. We strongly recommend that clinicians follow the Ponseti
      method as it initially was described without deviation to optimize treatment
      outcomes.

PMID- 24435717
TI  - Racial disparities at the point of care for urban children with persistent
      asthma.
AB  - Little is known about disparities in preventive asthma care delivery at the time
      of an office visit. Our objective was to better understand what treatments are
      delivered at the point of care for urban children with asthma, and whether there
      are racial disparities. We enrolled 100 Black and 77 White children (2-12 years)
      with persistent asthma from 6 primary care practices. We evaluated how frequently
      providers delivered guideline-based asthma actions at the index visit. We also
      assessed asthma morbidity prior to the index visit and again at 2 month follow
      up. Black children had greater symptom severity and were less likely to report
      having a preventive medication at baseline, but were no more likely to report a
      preventive medication action at the time of an office visit. Symptoms persisted
      for Black children at follow-up, suggesting additional preventive actions were
      needed. Further efforts to promote consistent guideline-based preventive asthma
      care are critical.

PMID- 24435718
TI  - Is functional manganese involved in hydrogen-peroxide-stimulated anomalous oxygen
      evolution in CACl2-washed photosystem II membranes?
AB  - When detergent-derived photosystem II (PSII) membranes are treated with CaCl2 to
      remove the three extrinsic proteins associated with the O2-evolving complex, the
      resulting membranes (CaPSII) can still catalyze water oxidation if sufficient
      Ca(2+) and Cl(-) are present. When CaPSII membranes are exposed to single
      turnover flashes on an O2 rate electrode, anomalous O2 is produced by the first
      two flashes. The addition of catalase to the membrane suspension completely
      inhibits O2 produced by the first two flashes, but not by subsequent flashes.
      Exogenous H2O2 stimulates anomalous O2 production by the first few flashes in
      CaPSII membranes, but not in control PSII membranes. Diuron (DCMU) does not
      inhibit H2O2-stimulated O2 production by the first flash. However, it does
      inhibit the O2 yield of all subsequent flashes, indicating that all flash-induced
      O2 signals in CaPSII membranes are dependent on photosystem II electron
      transport. H2O2 stimulation of O2 yields is inhibited in Tris-, heat-, and EDTA
      (ethylenediaminetetraacetic acid)-treated CaPSII. In the presence of high salt,
      H2O2 (but not EDTA) treatment of CaPSII, extracts Mn functional in normal
      photosynthetic O2 evolution. The addition of exogenous Mn(2+) reconstitutes
      anomalous O2 production in Tris-and H2O2/EDTA-treated CaPSII preparations but
      only in the presence of H2O2. Anomalous H2O2-stimulated O2 production can be
      observed both with a Clark electrode (steady state) and an O2 rate electrode
      (flash sequence). The mechanism involves electron donation from H2O2, mediated by
      free Mn(2+), to PSII, and the 33-kDa extrinsic protein under some conditions can
      block this process. Since H2O2 can remove functional Mn from CaPSII membranes,
      its presence can convert functional Mn to the Mn(2+) mediator state required for
      anomalous O2 production. EDTA binds Mn in CaPSII disrupted by H2O2 and prevents
      anomalous O2 evolution. 

PMID- 24435720
TI  - Comparison of photosystem II complexes isolated from tobacco and two chlorophyll
      deficient tobacco mutants.
AB  - A comparative study of photosystem II complexes isolated from tobacco (Nicotiana
      tabacum L. cv. John William's Broadleaf) which contains normal stacked thylakoid
      membranes, and from two chlorophyll deficient tobacco mutants (Su/su and Su/su
      var. Aurea) which have low stacked grana or essentially unstacked thylakoids with
      occasional membrane doublings, has been carried out. The corresponding
      photosystem II complexes had an O2 evolving activity ranging from 290 (for the
      wild type) to 1100 MUmol O2 x mg chlorophyll(-1) x h(-1) (for the mutant Su/su
      var. Aurea). The reduced photosynthetic unit size was also obvious in the
      mangenese and cytochromeb559 content. The photosystem II complex from the wild
      type contained 4 Mn and 1 cytochromeb559 per 200 to 280 chlorophylls, while the
      corresponding value for the mutant Su/su var. Aurea was 4 Mn and 1 cytochromeb559
      per 35 to 60 chlorophylls. We have also examined the polypeptide composition and
      show that the photosystem II complex from the wild type consisted of polypeptides
      of 48, 42, 33, 32, 30, 28, 23, 21, 18, 16 and 10 kDa, while the mutant complex
      mainly contained the polypeptides of 48, 42, 33, 32, 30, 28 and 10 kDa. In the
      mutant photosystem II complex the light-harvesting chlorophyll protein (peptide
      of 28 kDa) was reduced by a factor of 5 to 6 as compared to the wild type. With
      respect to the peptide composition and the photosynthetic unit size, the Triton
      solubilized photosystem II complex from the mutant Su/su var. Aurea was very
      similar to O2 evolving photosystem II reaction center core complexes. 

PMID- 24435719
TI  - State 1/State 2 changes in higher plants and algae.
AB  - Current ideas regarding the molecular basis of State 1/State 2 transitions in
      higher plants and green algae are mainly centered around the view that excitation
      energy distribution is controlled by phosphorylation of the light-harvesting
      complex of photosystem II (LHC-II). The evidence supporting this view is examined
      and the relationship of the transitions occurring in these systems to the
      corresponding transitions seen in red and blue-green algae is explored. 

PMID- 24435721
TI  - Kinetic study of P(F) and Car (T) states in the LM subunit purified from the wild
      type Rhodobacter sphaeroides reaction centers.
AB  - The kinetics of absorbance changes related to the charge-separated state, P(F),
      and to the formation and decay of the carotenoid triplet state (Car(T)) were
      studied in the LM reaction center subunit isolated from a wild-type strain of the
      purple bacterium Rhodobacter sphaeroides (strain Y). The P(F) lifetime is
      lengthened (20+/-1.5 ns) in the LM complex as compared to the intact reaction
      centers (11+/-1 ns). The yield of the carotenoid triplet formation is higher
      (0.28+/-0.01) in the LM complex than in native reaction centers. We interpret our
      results in terms of perturbations of a first-order reaction connecting the
      singlet and the triplet state of the radical-pair state. Our results, together
      with those of a recent work (Agalidis, I., Nuijs, A.M. and Reiss-Husson, F.
      (1987) Biochim. Biophys. Acta (in press)) are consistent with a high I to QA
      electron transfer rate in this LM subunit, which is metal-depleted.The LM complex
      is considerably more sensitive than the reaction centers to photooxidative damage
      in the presence of oxygen. This is not readily accounted for simply by the higher
      carotenoid triplet yield, and may suggest a greater accessibility of the internal
      structures in the absence of the H-subunit.The lifetime of the carotenoid triplet
      decay (6.4+/-0.3 MUs) in the LM subunit is unchanged compared to the native
      reaction centers. 

PMID- 24435722
TI  - Assocation of the 33 kDa extrinsic polypeptide (water-splitting) with PS II
      particles: immunochemical quantification of residual polypeptide after membrane
      extraction.
AB  - Various washing procedures were tested on Triton-prepared PS II particles for
      their ability to remove the 33 kDa extrinsic polypeptide (33 kDa EP) associated
      with the water-splitting complex. Residual 33 kDa EP was evaluated by Coomassie
      blue staining of SDS gels of washed particles and by Western blotting with an
      antibody specific for the 33 kDa EP. A wash with 16 mM Tris buffer, pH 8.3,
      inhibited water-splitting activity but did not remove all the 33 kDa EP.
      Sequential washes with 30 mM octyl glucoside (pH 8.0 and 6.8), and a single wash
      with 0.8 M Tris were also ineffective in removing all the 33 kDa EP. Washing with
      1 M CaCl2 was more effective in removing 33 kDa EP; while only a faint trace of
      protein was detectable by Coomassie-staining, immunoblotting revealed a
      considerable remainder. The treated particles retained some water-splitting
      activity. The two step procedure of Miyao and Murata (1984) involving 1 M NaCl
      and 2.3 M urea was most effective, removing all but a trace of antibody positive
      protein. Our finding suggests that (1) the degree of depletion of the 33 kDa EP
      cannot be judged on the basis of Coomassie stain alone, and (2) this extrinsic
      protein is very tightly associated with the membrane, perhaps via a hydrophilic
      portion of this otherwise hydrophilic protein. The results also suggest that the
      presence or absence of the 33 kDa protein per se is not the primary determinant
      of residual water splitting activity. 

PMID- 24435724
TI  - Letter to the editor.

PMID- 24435723
TI  - Effects of periodic fluctuations of photon flux density on anatomical and
      photosynthetic characteristics of soybean leaves.
AB  - The development of soybean leaves grown at fluctuating photon flux density
      between 100 and 1500MUM m(-2)s(-1) with a period of 160 sec were compared to
      leaves developed under continuous light with the same mean photon flux density.
      Number of epidermal cells and stomata, leaf area and specific leaf weight were
      not affected by the periodic fluctuation of photon flux density. Chloroplastic
      pigment concentration and chlorophyll fluorescence reveal some photoinhibitory
      effects of the high photon flux density phase. Stomatal and internal CO2
      conductance and the quantum yield were not affected by the light regime. In
      contrast ribulose 1.5 bisphosphate carboxylase/oxygenase activity before in vitro
      activation by CO2 and Mg(++) was stimulated by the periodic illumination whereas
      the total amount of the enzyme and the internal leaf CO2 conductance remained
      steady. In conclusion, there was no major difference between leaves of plant
      grown either under a steady or under a periodic fluctuation of the photon flux
      density except some photoinhibitory symptoms under fluctuating illumination, and
      a higher in vivo level of activation of the Rubisco. 

PMID- 24435725
TI  - Driver kinematic and muscle responses in braking events with standard and
      reversible pre-tensioned restraints: validation data for human models.
AB  - The objectives of this study are to generate validation data for human models
      intended for simulation of occupant kinematics in a pre-crash phase, and to
      evaluate the effect of an integrated safety system on driver kinematics and
      muscle responses. Eleven male and nine female volunteers, driving a passenger car
      on ordinary roads, performed maximum voluntary braking; they were also subjected
      to autonomous braking events with both standard and reversible pre-tensioned
      restraints. Kinematic data was acquired through film analysis, and surface
      electromyography (EMG) was recorded bilaterally for muscles in the neck, the
      upper extremities, and lumbar region. Maximum voluntary contractions (MVCs) were
      carried out in a driving posture for normalization of the EMG. Seat belt
      positions, interaction forces, and seat indentions were measured. During normal
      driving, all muscle activity was below 5% of MVC for females and 9% for males.
      The range of activity during steady state braking for males and females was 13
      44% in the cervical and lumbar extensors, while antagonistic muscles showed a co
      contraction of 2.3-19%. Seat belt pre-tension affects both the kinematic and
      muscle responses of drivers. In autonomous braking with standard restraints,
      muscle activation occurred in response to the inertial load. With pre-tensioned
      seat belts, EMG onset occurred earlier; between 71 ms and 176 ms after belt pre
      tension. The EMG onset times decreased with repeated trials and were shorter for
      females than for males. With the results from this study, further improvement and
      validation of human models that incorporate active musculature will be made
      possible.

PMID- 24435726
TI  - Effects of driver characteristics on seat belt fit.
AB  - A laboratory study of posture and belt fit was conducted with 46 men and 51
      women, 61% of whom were age 60 years or older and 32% age 70 years or older. In
      addition, 28% of the 97 participants were obese, defined as body mass index >= 30
      kg/m^2. A mockup of a passenger vehicle driver's station was created and five
      belt anchorage configurations were produced by moving the buckle, outboard-upper
      (D-ring), and outboard-lower anchorages. An investigator recorded the three
      dimensional locations of landmarks on the belt and the participant's body using a
      coordinate measurement machine. The location of the belt with respect to the
      underlying skeletal structures was analyzed, along with the length of belt
      webbing. Using linear regression models, an increase in age from 20 to 80 years
      resulted in the lap belt positioned 18 mm further forward relative to the pelvis,
      26 mm greater lap belt webbing length, and 19 mm greater shoulder belt length. An
      increase in stature of 350 mm (approximately the range from 5th-percentile female
      to 95th-percentile male in the U.S. population) was associated with the lap belt
      14 mm further forward relative to the pelvis, the shoulder belt 37 mm more
      outboard relative to the body centerline, and 38 mm less shoulder belt webbing
      length. Among the driver factors considered, body mass index had the greatest
      effects. An increase of BMI in 20 kg/m^2, which spans approximately the central
      90% of U.S. adults, was associated with the lap belt being placed 102 mm further
      forward and 94 mm higher, relative to the pelvis, and increases in lap and
      shoulder belt webbing length of 276 and 258 mm, respectively. Gender did not have
      important effects on the analyzed belt fit measures after taking into account
      stature and body mass index. These results offer important considerations for
      future crash safety assessments and suggest that further research is needed to
      consider belt fit for older and obese occupants.

PMID- 24435727
TI  - In vivo analysis of thoracic mechanical response variability under belt loading:
      specific behavior and relationship to age, gender and body mass index.
AB  - Thoracic injuries are a major cause of mortality in frontal collisions,
      especially for elderly female and obese people. Car occupant individual
      characteristics like age, gender and Body Mass Index (BMI) are known to influence
      human vulnerability tolerance in crashes. The objective of the this study was to
      perform in vivo test experiments to quantify the influence of subject
      characteristics in terms of age, gender and anthropometry and on thorax
      mechanical response variability under belt loading. Thirty-nine relaxed
      volunteers of different anthropometries, genders and age were submitted to non
      injurious sled tests (4 g, 8 km/h) with a sled buck representing the environment
      of a front passenger restrained by a 3-point belt. A resulting shoulder belt
      force FRes was computed using the external and internal shoulder belt loads and
      considering shoulder belt geometry. The mid sternal deflection D was calculated
      as the distance variation between markers placed at mid-sternum and at the 7th
      vertebra spinous process of the subject. Linear stiffness (K) and damping
      coefficient (MU) of a spring-dashpot model were identified from the FRes-D curves
      of each test. The analysis suggests that among subjects over 40 years old,
      thinness leads to higher K-values. 

PMID- 24435728
TI  - Biomechanical considerations for assessing interactions of children and small
      occupants with inflatable seat belts.
AB  - NHTSA estimates that more than half of the lives saved (168,524) in car crashes
      between 1960 and 2002 were due to the use of seat belts. Nevertheless, while seat
      belts are vital to occupant crash protection, safety researchers continue efforts
      to further enhance the capability of seat belts in reducing injury and fatality
      risk in automotive crashes. Examples of seat belt design concepts that have been
      investigated by researchers include inflatable, 4-point, and reverse geometry
      seat belts. In 2011, Ford Motor Company introduced the first rear seat inflatable
      seat belts into production vehicles. A series of tests with child and small
      female-sized Anthropomorphic Test Devices (ATD) and small, elderly female Post
      Mortem Human Subjects (PMHS) was performed to evaluate interactions of prototype
      inflatable seat belts with the chest, upper torso, head and neck of children and
      small occupants, from infants to young adolescents. Tests simulating a 6-year-old
      child asleep in a booster seat, with its head lying directly on its shoulder on
      top of the inflatable seat belt, were considered by engineering judgment, to
      represent a worst case scenario for interaction of an inflating seat belt with
      the head and neck of a child and/or small occupant. All evaluations resulted in
      ATD responses below Injury Assessment Reference Values reported by Mertz et al.
      (2003). In addition, the tests of the PMHS subjects resulted in no injuries from
      interaction of the inflating seat belt with the heads, necks, and chests of the
      subjects. Given the results from the ATD and PMHS tests, it was concluded that
      the injury risk to children and small occupants from deployment of inflatable
      seat belt systems is low. 

PMID- 24435729
TI  - Effect of vehicle front end profiles leading to pedestrian secondary head impact
      to ground.
AB  - Most studies of pedestrian injuries focus on reducing traumatic injuries due to
      the primary impact between the vehicle and the pedestrian. However, based on the
      Pedestrian Crash Data Study (PCDS), some researchers concluded that one of the
      leading causes of head injury for pedestrian crashes can be attributed to the
      secondary impact, defined as the impact of the pedestrian with the ground after
      the primary impact of the pedestrian with the vehicle. The purpose of this study
      is to understand if different vehicle front-end profiles can affect the risk of
      pedestrian secondary head impact with the ground and thus help in reducing the
      risk of head injury during secondary head impact with ground. Pedestrian
      responses were studied using several front-end profiles based off a mid-size
      vehicle and a SUV that have been validated previously along with several MADYMO
      pedestrian models. Mesh morphing is used to explore changes to the bumper height,
      bonnet leading-edge height, and bonnet rear reference-line height. Simulations
      leading up to pedestrian secondary impact with ground are conducted at impact
      speeds of 40 and 30 km/h. In addition, three pedestrian sizes (50th, 5th and 6yr
      old child) are used to enable us to search for a front-end profile that performs
      well for multiple sizes of pedestrians, not just one particular size. In most of
      the simulations, secondary ground impact with pedestrian head/neck/shoulder
      region occurred. However, there were some front-end profiles that promoted
      secondary ground impact with pedestrian lower extremities, thus avoiding
      pedestrian secondary head impact with ground. Previous pedestrian safety research
      work has suggested the use of active safety methods, such as 'pop up hood', to
      reduce pedestrian head injury during primary impact. Accordingly, we also
      conducted simulations using a model with the hood raised to capture the effect of
      a pop-up hood. These simulations indicated that even though pop-up hood helped
      reducing the head injury criterion during primary impact, it changed the overall
      pedestrian kinematics in some cases. The specific design with pop up hood
      evaluated in this study did not prevent pedestrian head secondary impact with the
      ground or actually led to more severe pedestrian secondary head impact with the
      ground. 

PMID- 24435730
TI  - Observations on pedestrian pre-crash reactions during simulated accidents.
AB  - Pedestrian protection systems, both active and passive systems, are being
      introduced in the EU and Japan to comply with regulatory requirements. Their
      designs are specific and, in general, reflect an accident scenario of the
      pedestrian being struck on the side by a vehicle traveling at a maximum travel
      speed of 40 kph. The present study is an effort to quantify the effects of
      pedestrian reaction prior to an accident and identify characteristics that may
      help minimize or prevent the pedestrian to vehicle interaction. Accident
      situations were simulated with volunteers using a non-impacting methodology.
      Fifty one reactions from 23 volunteers of two age groups were observed. Most of
      the volunteers were found to run, step-back or stop in fright in a dangerous
      situation. Volunteer speed was an important parameter which could help in
      differentiating these reactions. Age related differences were also observed, both
      for reaction strategy and reaction times. While the majority of young subjects
      ran, elderly stopped as often as they run. Volunteers' posture at the time of
      impact was found to be highly variable irrespective of the type of reactions. The
      exception was when a volunteer stopped/braced in apparent fright and raised their
      arms to form a triangle covering their face and their head. Results of the
      present study may be helpful when selecting or evaluating the benefit of
      pedestrian safety strategies by allowing the inclusion of information about types
      of reaction, pedestrian speed, reaction time and age differences in the
      scenarios. In addition, pedestrian pre-crash postures and muscle activities could
      be utilized for evaluating/improving the passive safety systems and active
      models. 

PMID- 24435731
TI  - Relationship between pedestrian headform tests and injury and fatality rates in
      vehicle-to-pedestrian crashes in the United States.
AB  - Pedestrian protection evaluations have been developed to encourage vehicle front
      end designs that mitigate the consequences of vehicle-to-pedestrian crashes. The
      European New Car Assessment Program (Euro NCAP) evaluates pedestrian head
      protection with impacts against vehicle hood, windshield, and A-pillars. The
      Global Technical Regulation No. 9 (GTR 9), being evaluated for U.S. regulation,
      limits head protection evaluations to impacts against vehicle hoods. The
      objective of this study was to compare results from pedestrian head impact
      testing to the real-world rates of fatal and incapacitating injuries in U.S.
      pedestrian crashes. Data from police reported pedestrian crashes in 14 states
      were used to calculate real-world fatal and in- capacitating injury rates for
      seven 2002-07 small cars. Rates were 2.17-4.04 per 100 pedestrians struck for
      fatal injuries and 10.45-15.35 for incapacitating injuries. Euro NCAP style
      pedestrian headform tests were conducted against windshield, A-pillar, and hoods
      of the study vehicles. When compared with pedestrian injury rates, the vehicles'
      Euro NCAP scores, ranging 5-10 points, showed strong negative correlations (-0.6)
      to injury rates, though none were statistically significant. Data from the
      headform impacts for each of the study vehicles were used to calculate that
      vehicle's predicted serious injury risk. The predicted risks from both the Euro
      NCAP and GTR 9 test zones showed high positive correlations with the pedestrian
      fatal and incapacitating injury rates, though few were statistically significant.
      Whether vehicle stiffness is evaluated on all components of vehicle front ends
      (Euro NCAP) or is limited to hoods (GTR 9), softer vehicle components correspond
      to a lower risk of fatality.

PMID- 24435732
TI  - Risks of pedestrian serious injuries and fatalities associated with impact
      velocities of cars in car-versus-pedestrian accidents in Japan.
AB  - The first purpose of this study is to clarify the relation between the car impact
      velocity and pedestrian injury severity or mortality risk. We investigated the
      frequency of serious injuries and fatalities of pedestrians using vehicle
      pedestrian accident data from the database of the Institute for Traffic Accident
      Research and Data Analysis (ITARDA) in Japan. The vehicle types considered are
      sedans, minivans, and box vans (ordinary automobiles) and light passenger cars
      and light cargo vans (light automobiles). The results revealed that a 10-km/h
      reduction in impact velocity could mitigate severe pedestrian injuries in cases
      involving impact velocities of 40 km/h or more for the five vehicle types
      analyzed. Specifically, if the impact velocity was 30 km/h or less, the frequency
      of serious injuries was less than 27% and the frequency of fatalities was less
      than 5% for the five vehicle types. Therefore, if the collision damage mitigation
      braking system (CDMBS) that uses a sensor to detect pedestrians can effectively
      reduce the impact velocity for various vehicle types, pedestrian injuries will be
      greatly mitigated. The second purpose of this study is to identify the factors
      that affect injury risk. Impact experiments were conducted in which a sedan
      impacted against a pedestrian full-scale dummy at 40 km/h and a pedestrian
      headform impactor was impacted against a road surface. The results indicated that
      the risk of pedestrian serious injury was significantly affected by multiple
      impact conditions, such as the pedestrian height, car impact velocity, car
      frontal shape, and car stiffness in cases where the car impacted the pedestrian's
      head, the degrees of influence of which were driven by the vehicle impact
      velocity. 

PMID- 24435733
TI  - The roles of mechanical compression and chemical irritation in regulating spinal
      neuronal signaling in painful cervical nerve root injury.
AB  - Both traumatic and slow-onset disc herniation can directly compress and/or
      chemically irritate cervical nerve roots, and both types of root injury elicit
      pain in animal models of radiculopathy. This study investigated the relative
      contributions of mechanical compression and chemical irritation of the nerve root
      to spinal regulation of neuronal activity using several outcomes. Modifications
      of two proteins known to regulate neurotransmission in the spinal cord, the
      neuropeptide calcitonin gene-related peptide (CGRP) and glutamate transporter 1
      (GLT-1), were assessed in a rat model after painful cervical nerve root injuries
      using a mechanical compression, chemical irritation or their combination of
      injury. Only injuries with compression induced sustained behavioral
      hypersensitivity (p<=0.05) for two weeks and significant decreases (p<0.037) in
      CGRP and GLT-1 immunoreactivity to nearly half that of sham levels in the
      superficial dorsal horn. Because modification of spinal CGRP and GLT-1 is
      associated with enhanced excitatory signaling in the spinal cord, a second study
      evaluated the electrophysiological properties of neurons in the superficial and
      deeper dorsal horn at day 7 after a painful root compression. The evoked firing
      rate was significantly increased (p=0.045) after compression and only in the
      deeper lamina. The painful compression also induced a significant (p=0.002) shift
      in the percentage of neurons in the superficial lamina classified as low-
      threshold mechanoreceptive (sham 38%; compression 10%) to those classified as
      wide dynamic range neurons (sham 43%; compression 74%). Together, these studies
      highlight mechanical compression as a key modulator of spinal neuronal signaling
      in the context of radicular injury and pain. 

PMID- 24435734
TI  - Development of brain injury criteria (BrIC).
AB  - Rotational motion of the head as a mechanism for brain injury was proposed back
      in the 1940s. Since then a multitude of research studies by various institutions
      were conducted to confirm/reject this hypothesis. Most of the studies were
      conducted on animals and concluded that rotational kinematics experienced by the
      animal's head may cause axonal deformations large enough to induce their
      functional deficit. Other studies utilized physical and mathematical models of
      human and animal heads to derive brain injury criteria based on
      deformation/pressure histories computed from their models. This study differs
      from the previous research in the following ways: first, it uses two different
      detailed mathematical models of human head (SIMon and GHBMC), each validated
      against various human brain response datasets; then establishes physical (strain
      and stress based) injury criteria for various types of brain injury based on
      scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs)
      (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs,
      WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and
      frontal offset tests) to establish a kinematically based brain injury criterion
      (BrIC) for all ATDs. Similar procedures were applied to college football data
      where thousands of head impacts were recorded using a six degrees of freedom (6
      DOF) instrumented helmet system. Since animal injury data used in derivation of
      BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently
      an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal
      strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries.
      The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using
      the ratios between corresponding risk curves for head injury criterion (HIC) at a
      50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk
      curves using the linear relationship between CSDM - BrIC and MPS - BrIC
      respectively. AIS 3+, 4+ and 5+ field risk of anatomic brain injuries was also
      estimated using the National Automotive Sampling System - Crashworthiness Data
      System (NASS-CDS) database for crash conditions similar to the frontal NCAP and
      side impact conditions that the ATDs were tested in. This was done to assess the
      risk curve ratios derived from HIC risk curves. The results of the study
      indicated that: (1) the two available human head models - SIMon and GHBMC - were
      found to be highly correlated when CSDMs and max principal strains were compared;
      (2) BrIC correlates best to both - CSDM and MPS, and rotational velocity (not
      rotational acceleration) is the mechanism for brain injuries; and (3) the
      critical values for angular velocity are directionally dependent, and are
      independent of the ATD used for measuring them. The newly developed brain injury
      criterion is a complement to the existing HIC, which is based on translational
      accelerations. Together, the two criteria may be able to capture most brain
      injuries and skull fractures occurring in automotive or any other impact
      environment. One of the main limitations for any brain injury criterion,
      including BrIC, is the lack of human injury data to validate the criteria
      against, although some approximation for AIS 2+ injury is given based on the
      angular velocities calculated at 50% probability of concussion in college
      football players instrumented with 5 DOF helmet system. Despite the limitations,
      a new kinematic rotational brain injury criterion - BrIC - may offer a way to
      capture brain injuries in situations when using translational accelerations based
      HIC alone may not be sufficient. 

PMID- 24435735
TI  - The quantification of liver anatomical changes and assessment of occupant liver
      injury patterns.
AB  - Liver injuries can be significant in vehicle crashes. In this study, the liver
      anatomy was quantified in both adult and pediatric populations as a function of
      gender and age. Five anatomical liver measurements were determined using CT scans
      of 260 normal livers. These measurements include the area and volume, and the
      length, width, and girth of the liver (IRB HUM00041441). To characterize
      geometrical shape, an inscribed sphere and circumscribed ellipsoid were fitted on
      the measurements. In the pediatric population the liver area and volume
      continuously increased with age. When normalized by patient weight, volume
      measurements show a decrease in volume with age, suggesting that the liver
      occupies a smaller proportion of the body with age. In the adult population,
      liver measurements varied with gender. The superior and inferior locations of the
      liver were also recorded with respect to the spine. The lower portion was at the
      L3 in small children and at L2 as children approached puberty. It stayed in that
      area through the 60+ group, offering more ribcage protection. Liver injury
      patterns were also assessed in crash occupants. Seventy-two occupants with
      moderate to severe (AIS 2+) liver injuries were investigated. A new methodology
      was presented and consisted of quantifying blood volumes. The results were
      compared to overall liver volume and injury scales. No clear distinction on the
      injury pattern was observed by age group. Liver injuries were more commonly
      associated with AIS 2+ thoracic injuries in adults than in children. Most
      injuries occurred in the right lobe. 

PMID- 24435736
TI  - Statistical modeling of human liver incorporating the variations in shape, size,
      and material properties.
AB  - The liver is one of the most frequently injured abdominal organs during motor
      vehicle crashes. Realistic numerical assessments of liver injury risk for the
      entire occupant population require incorporating inter-subject variations into
      numerical models. The main objective of this study was to quantify the shape
      variations of human liver in a seated posture and the statistical distributions
      of its material properties. Statistical shape analysis was applied to construct
      shape models of the livers of 15 adult human subjects, recorded in a typical
      seated (occupant) posture. The principal component analysis was then utilized to
      obtain the modes of variation, the mean model, and 95% statistical boundary shape
      models. In addition, a total of 52 tensile tests were performed on the parenchyma
      of three fresh human livers at four loading rates (0.01, 0.1, 1, and 10 s^-1) to
      characterize the rate-dependent and failure properties of the human liver. A FE
      based optimization approach was employed to identify the material parameters of
      an Ogden material model for each specimen. The mean material parameters were then
      determined for each loading rate from the characteristic averages of the stress
      strain curves, and a stochastic optimization approach was utilized to determine
      the standard deviations of the material parameters. Results showed that the first
      five modes of the human liver shape models account for more than 60% of the
      overall anatomical variations. The distributions of the material parameters
      combined with the mean and statistical boundary shape models could be used to
      develop probabilistic finite element (FE) models, which may help to better
      understand the variability in biomechanical responses and injuries to the
      abdominal organs under impact loading. 

PMID- 24435737
TI  - Volunteer kinematics and reaction in lateral emergency maneuver tests.
AB  - It is important to understand human kinematics and muscle activation patterns in
      emergency maneuvers for the design of safety systems and for the further
      development of human models. The objective of this study was to quantify
      kinematic behavior and muscle activation in simulated steering tests in several
      realistic conditions. In total 108 tests were performed with 10 volunteers
      undergoing purely lateral maneuvers at 5 m/s^2 deceleration or simulated lane
      change maneuvers at 5 m/s^2 peak acceleration and peak yaw velocity of 25 
      degrees /s. Test subjects were seated on a rigid seat and restrained by a 4-point
      belt with retractor. Driver subjects were instructed to be relaxed or braced and
      to hold the steering wheel while passenger subjects were instructed to put their
      hands on their thighs. Subjects were instrumented with photo markers that were
      tracked with 3D high- speed stereo cameras and with electromyography (EMG)
      electrodes on 8 muscles. Corridors of head displacement, pitch and roll and
      displacement of T1, shoulder, elbow, hand and knee were created representing mean
      response and standard deviation of all subjects. In lane change tests for the
      passenger configuration significant differences were observed in mean peak of
      head left lateral displacement between the relaxed and the braced volunteers,
      i.e. 171 mm (sigma=58, n=21) versus 121 mm (sigma=46, n=17), respectively.
      Sitting in a relaxed position led to significantly lower muscle activity of the
      neck muscles. It was concluded that significantly more upper body motion and
      lower muscle activity was observed for relaxed subjects than for braced subjects.

PMID- 24435738
TI  - Occupant kinematics and shoulder belt retention in far-side lateral and oblique
      collisions: a parametric study.
AB  - In far-side impacts, head contact with interior components is a key injury
      mechanism. Restraint characteristics have a pronounced influence on head motion
      and injury risk. This study performed a parametric examination of restraint,
      positioning, and collision factors affecting shoulder belt retention and occupant
      kinematics in far-side lateral and oblique sled tests with post mortem human
      subjects (PMHS). Seven PMHS were subjected to repeated tests varying the D-ring
      position, arm position, pelvis restraint, pre-tensioning, and impact severity.
      Each PMHS was subjected to four low-severity tests (6.6 g sled acceleration
      pulse) in which the restraint or position parameters were varied and then a
      single higher-severity test (14 g) with a chosen restraint configuration (total
      of 36 tests). Three PMHS were tested in a purely lateral (90 degrees  from
      frontal) impact direction; 4 were tested in an oblique impact (60 degrees  from
      frontal). All subjects were restrained by a 3-point seatbelt. Occupant motion was
      tracked with a 3D optoelectric high speed motion capture system. For all
      restraint configurations, the 60 degrees  oblique impact angle was associated
      with greater lateral head excursion than the 90 degrees  impact angle. This
      unexpected result reflects the increased axial rotation of the torso in the
      oblique impacts, which allowed the shoulder to displace more relative to the
      shoulder belt and thus the head to displace more relative to the sled buck.
      Restraint engagement of the torso and shoulder was actually greater in the purely
      lateral impacts than in the oblique impacts. Pretensioning significantly reduced
      lateral head excursion (175 mm average in the low-severity tests across all
      restraint configurations). 

PMID- 24435739
TI  - PMHS impact response in 3 m/s and 8 m/s nearside impacts with abdomen offset.
AB  - Lateral impact tests were performed using seven male post-mortem human subjects
      (PMHS) to characterize the force-deflection response of contacted body regions,
      including the lower abdomen. All tests were performed using a dual-sled, side
      impact test facility. A segmented impactor was mounted on a sled that was
      pneumatically accelerated into a second, initially stationary sled on which a
      subject was seated facing perpendicular to the direction of impact. Positions of
      impactor segments were adjusted for each subject so that forces applied to
      different anatomic regions, including thorax, abdomen, greater trochanter, iliac
      wing, and thigh, could be independently measured on each PMHS. The impactor
      contact surfaces were located in the same vertical plane, except that the abdomen
      plate was offset 5.1 cm towards the subject. The masses of the sleds and the
      force- deflection characteristics of the energy-absorbing interface material
      between the sleds were set to provide the impactor sled with a velocity profile
      that matched the average driver door velocity history produced in a series of
      side NCAP tests. Impactor padding was also selected so that average ATD pelvis
      and thorax responses from the same series of side NCAP tests were reproduced when
      the ATD used in these tests was impacted using the average door-velocity history.
      Each subject was first impacted on one side of the body using an initial impactor
      speed of 3 m/s. If a post-test CT scan and strain-gage data revealed two or fewer
      non-displaced rib fractures, then the PMHS was impacted on the contralateral side
      of the body at a speed of 8 m/s or 10 m/s. The results of tests in the 3 m/s and
      8 m/s conditions were used to develop force-deflection response corridors for the
      abdomen, force history response corridors for the pelvis (iliac wing and greater
      trochanter), the midthigh, and the thorax. Response corridors for the lateral
      acceleration of the pelvis were also developed. Future work will compare side
      impact ATD responses to these response corridors. 

PMID- 24435740
TI  - Oblique lateral impact biofidelity deflection corridors from Post Mortem Human
      Surrogates.
AB  - The objective of the study was to determine the thorax and abdomen deflection
      time corridors in oblique side impacts. Data were analyzed from Post Mortem Human
      Surrogate (PMHS) sled tests, certain aspects of which were previously published.
      A modular and scalable anthropometry-specific segmented load-wall system was
      fixed to the platform of the sled. Region-specific forces were recorded from load
      cells attached to the load-wall plates. The thorax and abdomen regions were
      instrumented with chestbands, and deflection contours were obtained.
      Biomechanical responses were processed using the impulse-momentum normalization
      method and scaled to the mid-size male mass, 76-kg. The individual effective
      masses of the thorax and abdomen were used to determine the scale factors in each
      sled test, thus using the response from each experiment. The maximum deflections
      and their times of attainments were obtained, and mean and plus minus one
      standard deviation corridors were derived. Test-by-test thorax and abdomen force
      time histories are given. Deflection-time histories for each specimen for the two
      body regions and corridors are presented. The mean maximum deflections for the
      thorax and abdomen body regions were 68.41 +/- 16.1 and 68.98 +/- 12.69 mm,
      respectively. Deflections were greater in oblique than pure lateral loading tests
      for both body regions, indicating the increased sensitivity of oblique side
      impact vector to the human response. The mean and one standard deviation
      responses of the thorax and abdomen serve as biofidelity corridors under oblique
      loading. Because modern instrumentation techniques can accommodate deflection
      sensors in the thorax and abdomen in devices such as WorldSID, and computer
      finite element models are flexible enough to extract regional and local
      deformation fields, the present data can be used to evaluate dummy biofidelity
      and validate and verify numerical models. They can be used to advance injury
      assessment reference values in oblique impacts. 

PMID- 24435741
TI  - Opportunities for injury reduction in US frontal crashes: an overview by
      structural engagement, vehicle class, and occupant age.
AB  - An overview NASS study of US frontal crashes was performed to investigate crash
      involvement, driver injury distributions and rates in airbag equipped vehicles by
      vehicle class and structural engagement. Frontal crash bins were based on
      taxonomy of structural engagement, i.e., Full Engagement, Offset, Between Rails
      and Corner impact crashes. A new classification of Corner impacts included
      frontal small overlap impacts with side damage as coded by NASS CDS. Belted
      drivers of two age groups, between 16 and 50 and over 50 years old, were
      considered. Vehicles were grouped into light and heavy passenger cars and lights
      trucks, and vans. A method to identify and address overly influential NASS
      weights was developed based on considerations of weighting factor statistics. The
      new taxonomy, with an expanded definition of corner impacts, allowed a more
      comprehensive classification of frontal crash modes. Results highlight the need
      to address upper extremities injuries and to better address lower extremities
      injuries for both the younger and older drivers. For all body regions studied,
      the vast majority of all serious and moderate injuries occurred in Full
      Engagement and Offset crash modes for both the younger and older drivers. Corner
      impacts, which have been the focus of recent research and testing programs, are
      the smallest contributors to serious and moderate injuries in frontal crashes.
      Greater opportunities to mitigate injuries in frontal crashes for vehicles have
      been shown to exist in lower speed full frontal and offset crash modes. 

PMID- 24435742
TI  - Assessing biofidelity of the Test Device for Human Occupant Restraint (THOR)
      against historic human volunteer data.
AB  - The National Aeronautics and Space Administration (NASA) is interested in
      characterizing the responses of THOR (test device for human occupant restraint)
      anthropometric test device (ATD) to representative loading acceleration pulses.
      Test conditions were selected both for their applicability to anticipated NASA
      landing scenarios, and for comparison to human volunteer data previously
      collected by the United States Air Force (USAF). THOR impact testing was
      conducted in the fore-to-aft frontal (-x) and in the upward spinal (-z)
      directions with peak sled accelerations ranging from 8 to 12 G and rise times of
      40, 70, and 100ms. Each test condition was paired with historical human data sets
      under similar test conditions that were also conducted on the HIA. A correlation
      score was calculated for each THOR to human comparison using CORA (CORrelation
      and Analysis) software. A two-parameter beta distribution model fit was obtained
      for each dependent variable using maximum likelihood estimation. For frontal
      impacts, the THOR head x-acceleration peak response correlated with the human
      response at 8 and 10G 100ms, but not 10G 70ms. The phase lagged the human
      response. Head z-acceleration was not correlated. Chest x-acceleration was in
      phase, had a higher peak response, and was well correlated with lighter subjects
      (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126kg). Head x-displacement had a
      leading phase. Several subjects responded with the same peak displacement, but
      the mean of the group was lower. The shoulder x-displacement was in phase but had
      higher peaks than the human response. For spinal impacts, the THOR head x
      acceleration was not well correlated. Head and chest z-acceleration was in phase,
      but had a higher peak response. Chest z-acceleration was highly correlated with
      heavier subjects at lower G pulses (Cora = 0.86 for 125kg at 8G). The human
      response was variable in should z-displacement, but the THOR was in phase and was
      comparable to the mean peak response. Head x- and z-displacement was in phase,
      but had higher peaks. Seat pan forces are well correlated, are in phase, but have
      a larger peak response than most subjects. 

PMID- 24435744
TI  - No association between TMJ joint clicking and malocclusion features in a patient
      sample analyzed by logistic regression.

PMID- 24435745
TI  - Lack of association of XRCC1 rs1799782 genetic polymorphism with risk of
      pancreatic cancer: a meta-analysis.
AB  - Emerging evidence suggests that genetic polymorphisms in X-ray repair cross
      complementation group 1 (XRCC1) gene could be associated with pancreatic cancer
      risk. However, previous published studies on the association between XRCC1
      rs1799782 genetic polymorphism and pancreatic cancer risk reported inconsistent
      results. For better understanding of the effects of XRCC1 rs1799782 genetic
      polymorphism on pancreatic cancer risk, we conducted a meta-analysis of previous
      published studies by calculating the pooled odds ratio (OR) with a 95% confidence
      interval (95% CI). A total of five eligible studies with 1,144 pancreatic cancer
      cases and 2,925 controls were eventually enrolled. Overall, we found that the
      XRCC1 rs1799782 genetic polymorphism was not associated with pancreatic cancer
      risk in total population under all genetic models (TT vs. CC: OR = 1.11, 95% CI
      0.76-1.63, P = 0.583; CT vs. CC: OR = 1.39, 95% CI 0.92-2.10, P = 0.118; TT/CT
      vs. CC: OR = 1.39, 95% CI 0.92-2.10, P = 0.121; TT vs. CT/CC: OR = 1.07, 95% CI
      0.73-1.55, P = 0.743; T vs. C: OR = 1.31, 95% CI 0.93-1.86, P = 0.125). In the
      subgroup analysis based on ethnicity, there was no statistically significant
      association between XRCC1 rs1799782 genetic polymorphism and pancreatic cancer
      risk in Asians/Caucasians under all genetic models (all P values > 0.05). No
      publication bias was detected in this study. Our meta-analysis suggests that the
      XRCC1 rs1799782 genetic polymorphism is not significantly associated with
      pancreatic cancer risk. Considering the limited sample size and ethnicity
      enrolled in this meta-analysis, further larger scaled studies are needed to
      provide a more precise estimation on the association.

PMID- 24435746
TI  - Prostate cell lines as models for biomarker discovery: performance of current
      markers and the search for new biomarkers.
AB  - BACKGROUND: Prostate cancer cell lines have been used in the search for
      biomarkers that are suitable for prostate cancer diagnosis. Unfortunately, many
      cell line studies have only involved single cell lines, partially characterized
      cell lines or were performed without controls, and this may have been detrimental
      to effective biomarker discovery. We have analyzed a panel of prostate cancer and
      nonmalignant control cell lines using current biomarkers and then investigated a
      set of prospective endosomal and lysosomal proteins to search for new biomarkers.
      METHODS: Western blotting was used to define the amount of protein and specific
      molecular forms in cell extracts and culture media from a panel of nonmalignant
      (RWPE-1, PNT1a, PNT2) and prostate cancer (22RV1, CaHPV10, DU-145, LNCaP) cell
      lines. Gene expression was determined by qRT-PCR. RESULTS: HPV-18 transfected
      cell lines displayed a different pattern of protein and gene expression when
      compared to the other cell lines examined, suggesting that these cell lines may
      not be the most optimal for prostate cancer biomarker discovery. There was an
      increased amount of prostatic acid phosphatase and kallikrein proteins in LNCaP
      cell extracts and culture media, but variable amounts of these proteins in other
      prostate cancer cell lines. There were minimal differences in the amounts of
      lysosomal proteins detected in prostate cancer cells and culture media, but two
      endosomal proteins, cathepsin B and acid ceramidase, had increased gene and
      protein expression, and certain molecular forms showed increased secretion from
      prostate cancer cells (P <= 0.05). LIMP-2 gene and protein expression was
      significantly increased in prostate cancer compared to nonmalignant cell lines (P
      <= 0.05). CONCLUSIONS: While the existing prostate cancer biomarkers and
      lysosomal proteins investigated here were not able to specifically differentiate
      between a panel of nonmalignant and prostate cancer cell lines, endosomal
      proteins showed some discriminatory capacity. LIMP-2 is a critical regulator of
      endosome biogenesis and the increased expression observed in prostate cancer
      cells indicated that other endosome related proteins may also be upregulated and
      could be investigated as novel biomarkers.

PMID- 24435748
TI  - Y-chromosome hyperploidy in Rumex.
AB  - 1. Male and female Y-chromosome hyperploid plants were obtained and
      morphologically and cytologically investigated. 2. Conjugation of sex chromosomes
      was investigated in ? plants with 1, 2 and 3 additional Y chromosomes.
      Conjugation between sex chromosomes was end-to-end. Association between Y
      chromosomes was partly based on conjugation between homologous segments and
      partly due to heterochromatin fusion. 3. Transmission of the additional Y
      chromosome to the progeny was studied. In all cases transmission of the extra Y
      chromosome was very low. The reasons for this phenomenon are probably nonrandom
      fertilization, nonrandom degeneration of megaspore, and reduced seed setting and
      seed fertility in plants with additional Y chromosomes. 4. The phenotypic effect
      of Y chromosome hyperploidy was investigated. Plants with extra Y chromosomes are
      shorter and die earlier. The fertility of such plants is low. Thus, although Y
      chromosomes are heterochromatic and nonactive (except in the premeiotic
      interphase of microsporogenesis) they have a marked influence on the appearance
      of Y-chromosome hyperploid plants. 

PMID- 24435747
TI  - Expression of a single ICAM-1 isoform on T cells is sufficient for development of
      experimental autoimmune encephalomyelitis.
AB  - Intercellular adhesion molecule-1 (ICAM-1) plays an important role in leukocyte
      trafficking, induction of cellular immune responses, and immunological synapse
      formation. As a member of the immunoglobulin superfamily of adhesion proteins,
      ICAM-1 is composed of repeating Ig-like domains, a transmembrane domain, and
      short cytoplasmic tail that participates in intracellular signaling events. At
      least seven ICAM-1 protein isoforms are generated by alternative splicing,
      however little is known regarding their immunobiology. We have previously shown
      using different lines of ICAM-1 mutant mice (Icam1(tm1Jcgr) and Icam1(tm1Bay) )
      that expression of alternatively spliced ICAM-1 isoforms can significantly
      influence the disease course during the development of EAE. In this study, we
      show using a newly developed transgenic mouse (CD2-Icam1(D4del) /Icam1(null) )
      that T-cell-specific expression of a single ICAM-1 isoform composed of Ig domains
      1, 2, 3, and 5 can mediate the initiation and progression of EAE. Our results
      indicate that the ICAM-1 isoform lacking Ig domain 4 can drive pathogenesis in
      demyelinating disease and may be a novel therapeutic target for treating multiple
      sclerosis. 

PMID- 24435749
TI  - [Chromosome numbers in the progenies of pentaploid plants in the section
      Corollinae of Beta].
AB  - In progenies of isolated pentaploid plants of the section Corollinae of Beta
      pentaploids only have been found, with the exception of one octoploid plant which
      may have arisen due to insufficient isolation. After open pollination, the same
      pentaploid mother plants showed, in their progenies, hepta- and octoploid plants
      besides the more common pentaploids. It is concluded that in pentaploids
      fertilization of unreduced egg cells occurs in addition to the more common
      apomictic propagation. In our example the pollen is that of neighbouring tetra-
      and hexaploid plants. It is suggested that pentaploids arose by fertilization of
      unreduced egg cells of tetraploids by pollen of diploid Beta lomatogona. 

PMID- 24435750
TI  - Genetic correlation and response to selection in simulated populations : III.
      Correlated response to selection.
AB  - One of two quantitative traits was selected and correlated response in the other
      trait was measured in each of 30 generations for models of additive genes and of
      complete dominance. Each trait was controlled by 48 loci with equal effects,
      segregating independently from frequencies of 0.5 in the initial generation.
      Intensity of selection regulated the number of offspring from randomly mating 24
      males and 24 females each generation. Three each of genetic correlations between
      traits, intensities of selection, and amounts of environmental variation were
      simulated.In the additive model correlated responses of the unselected trait to
      selection of the primary trait agreed closely with responses expected from
      theoretical considerations. In the model of complete dominance, responses of
      genotypic means of the unselected trait to selection of the primary trait in
      opposite directions were quite symmetrical for the first few generations but
      became distinctly asymmetrical in later generations. With little selection,
      response was fairly linear but became distinctly curvilinear as intensity of
      selection increased and environmental variance decreased. Between 15th and 30th
      generations some gains in the correlated trait to the 15th generation were lost. 

PMID- 24435751
TI  - Colchicine induced polyploidy in chickpeas (Cicer arietinum L.).
AB  - The most successful induction of tetraploidy was obtained with 2 hour treatment
      by 0.25% aqueous colchicine solution of 18-hour watersoaked desi chickpeas
      material. However, kabuli types needed only 1 hour treatment under similar
      conditions. Gigantism accompanied induction of polyploidy in desi as well as
      kabuli types but yield and fertility were greatly reduced. The meiotic
      abnormalities accompanying polyploidy were multivalent association of chromosomes
      followed by unequal disjunction, chromosome bridges, laggards etc. The percentage
      of stainable pollen, however, was at par between diploids and tetraploids. Gene
      control of percentage seed setting was observed in both levels of ploidy. A
      striking feature of the studies was the high seed setting percentage in 4n F 1
      material resulting from diverse crosses, viz., desi*kabuli. A probable reduction
      in multivalent association coupled with yield increases in segregants from the
      later generation of tetraploids indicates the possibility of selection for higher
      yield and fertility from polyploids, particularly from some hybrid material. 

PMID- 24435752
TI  - [Investigation of a genetically determined physiological characteristic of two
      strains of cultivated mushrooms for its suitability as a basis for early
      selection following cross-breeding].
AB  - The different growth response of two strains of cultivated mushrooms (a cream
      colored and a white one), on malt agar was tested to determine its suitability
      for selection following cross-breeding. While the white strain always grew faster
      on malt agar than did the cream-colored one, the progeny of each strain no longer
      showed this dependence on the nutrient medium. Progeny of several white mushrooms
      which had originated by mutation in a cream-colored strain were tested also.
      These mushrooms have a white cap but retain the more robust growth habit
      characteristic of the cream-colored strain. On malt agar they grow no faster than
      does the cream-colored strain. The characteristic described cannot be used as a
      basis for selection following crosses of cream-colored * white varieties, since
      cap color and mycelial growth habit are determined by different genes. 

PMID- 24435753
TI  - The effect of cycloheximide and 6-methylpurine on in vivo compatible and
      incompatible pollen tube growth in Lilium longiflorum.
AB  - Cycloheximide, a potent inhibitor of protein synthesis, placed in styles of
      Lilium longiflorum at 10(-4) M in stigmatic exudate before, 6, or 12 hr after
      compatible or incompatible pollination retarded all pollen tube growth. An
      inhibitor of RNA synthesis, 6-methylpurine, placed in the style at 10(-4) M in
      stigmatic exudate before, 6, or 12 hr after pollination restricted compatible
      pollen tube growth to lengths not significantly different thanincompatiblepollen
      tubes in treated or nontreated styles. While pollen tube growth in the style of
      L. longiflorum appears to require protein synthesis, only compatible pollen tube
      growth requires RNA synthesis. Stigmatic exudate proved to be an excellent
      carrier of exogenous substances into the style of L. longiflorum. 

PMID- 24435754
TI  - Peroxidase activity in Linum usitatissimum L.
AB  - Crosses were made, in all combinations, between 2 parental genotypes of Linum and
      their reciprocal F 1 hybrids. The parents and progeny obtained were grown in
      controlled environmental conditions and sampled at 35 and 70 days after
      germination to determine, on an individual plant basis, total plant fresh weight
      and peroxidase activity of main stem tissue. Peroxidase activity required
      transformation to a log10 scale, whereas the original linear scale was
      satisfactory for plant weight. There was no correlation between plant weight and
      corresponding peroxidase activity. Pronounced heterosis appeared in the F 1's for
      both characters at sample 1, but this heterosis had declined at sample 2 and in
      the F 2's. Heterosis operated in a positive direction for plant weight and in a
      negative direction for peroxidase activity. No consistent differences were found
      amongst the variances of segregating or non-segregating generations for either
      character. 

PMID- 24435755
TI  - Paramutation and mutation of R (ch) in maize.
AB  - 1. In maize, R (ch) conditions anthocyanin pigmentation in aleurone, anthers,
      silks and reacts with another factor Pl to produce cherrycoloured pericarp, thus
      representing the broadest pigmentation pattern among all the alleles at the R
      locus. The paramutational and mutational behaviour of R (ch) are reported here.
      2. R (ch) is paramutable with respect to its action in the aleurone, but its
      pigmenting ability in the pericarp is not sensitive to the paramutagenic action
      of R (st) . 3. The mutation experiments revealed that R (ch) is a compound locus
      containing at least four different components: (P) affecting anthocyanin in
      anthers, (Si) conditioning pink silks, (Ch) reacting with Pl to produce cherry
      pericarp, and (S) affecting aleurone pigmentation. 4. Different interactions of R
      (ch) with independent genes support the conclusions drawn from mutation
      experiments. 5. It is suggested that different components of the R (ch) locus are
      unequally sensitive to the action of R (st) . 

PMID- 24435756
TI  - 17beta-Estradiol protects against apoptosis induced by levofloxacin in rat
      nucleus pulposus cells by upregulating integrin alpha2beta1.
AB  - Levofloxacin has been reported to have cytotoxicity to chondrocytes in vitro. And
      17beta-estradiol has been widely studied for its protective effects against cell
      apoptosis. Based on apoptotic cell model induced by levofloxacin, the purpose of
      this study was to explore the mechanism by which 17beta-estradiol protects rat
      nucleus pulposus cells from apoptosis. Inverted phase-contrast microscopy, flow
      cytometry, and caspase-3 activity assay were used to find that levofloxacin
      induced marked apoptosis, which was abolished by 17beta-estradiol. Interestingly,
      estrogen receptor antagonist, ICI182780, and functional blocking antibody to
      alpha2beta1 integrin, both prohibited the effect of 17beta-estradiol.
      Simultaneously, levofloxacin decreased cellular binding ability to type II
      collagen, which was also reversed by 17beta-estradiol. Furthermore, western blot
      and real-time quantitative PCR were used to find that integrin alpha2beta1 was
      responsible for estrogen-dependent anti-apoptosis, which was time-response and
      dose-response effect. 17beta-estradiol was proved for the first time to protect
      rat nucleus pulposus cells against levofloxacin-induced apoptosis by upregulating
      integrin alpha2beta1 signal pathway.

PMID- 24435757
TI  - A positive role of microRNA-15b on regulation of osteoblast differentiation.
AB  - Osteoblast differentiation is tightly regulated by several factors including
      microRNAs (miRNAs). In this paper, we report that pre-mir-15b is highly expressed
      in differentiated osteoblasts. The functional role of miR-15b in osteoblast
      differentiation was determined using miR-15b mimic/inhibitor and the expression
      of osteoblast differentiation marker genes such as alkaline phosphatase (ALP),
      type I collagen genes was decreased by miR-15b inhibitor. Runx2, a bone specific
      transcription factor is generally required for expression of osteoblast
      differentiation marker genes and in response to miR-15b inhibitor treatment,
      Runx2 mRNA expression was not changed; whereas its protein expression was
      decreased. Even though Smurf1 (SMAD specific E3 ubiquitin protein ligase 1),
      HDAC4 (histone deacetylase 4), Smad7, and Crim1 were found to be few of miR-15b's
      putative target genes, there was increased expression of only Smurf1 gene at mRNA
      and protein levels by miR-15b inhibitor. miR-15b mimic treatment significantly
      increased and decreased expressions of Runx2 and Smurf1 proteins, respectively.
      We further identified that the Smurf1 3'UTR is directly targeted by miR-15b using
      the luciferase reporter gene system. This is well documented that Smurf1
      interacts with Runx2 and degrades it by proteasomal pathway. Hence, based on our
      results we suggest that miR-15b promotes osteoblast differentiation by indirectly
      protecting Runx2 protein from Smurf1 mediated degradation. Thus, this study
      identified that miR-15b can act as a positive regulator for osteoblast
      differentiation.

PMID- 24435758
TI  - Understanding the beneficial effects of doxycycline on the dystrophic phenotype
      of the mdx mouse.
AB  - INTRODUCTION: The purpose of this study was to better understand the beneficial
      effects of doxycycline on the dystrophic muscles of the mdx mouse. METHODS:
      Doxycycline (DOX) was administered for 36 days, starting on postnatal day 0, via
      drinking water. Untreated mdx mice received plain water for the same period and
      served as a control group. RESULTS: DOX decreased the levels of metalloproteinase
      9 and tumor necrosis factor-alpha in the biceps brachii and diaphragm of the mdx
      mice. It also reduced the total amount of calcium in the muscles studied,
      concomitant with an increase in the levels of calsequestrin 1. CONCLUSIONS: The
      results show that DOX can affect factors that are important in dystrophic
      pathogenesis and highlight its potential as a readily accessible therapy in
      clinical trials for treatment of Duchenne muscular dystrophy.

PMID- 24435759
TI  - Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a
      pharmacokinetic and bioequivalence study.
AB  - BACKGROUND: The objectives of this study were to investigate pharmacokinetic and
      pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a
      twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in
      pediatric kidney transplant recipients. METHODS: Twenty-four-hour pharmacokinetic
      profiles were analyzed before and after conversion in 19 stable renal transplant
      recipients (age 7-19 years). Tacrolimus pharmacokinetic parameters [area under
      the concentration-time curve (AUC0-24), minimum whole-blood concentration (Cmin),
      maximum whole-blood concentration (Cmax), and time to achieve maximum whole-blood
      concentration (tmax)] were compared between Tac formulations and between CYP3A5
      and MDR1 genotypes after dose normalization. RESULTS: Both AUC0-24 and Cmin
      decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p = 0.03
      and 0.01, respectively). However, the ratio of the least square means (LSM) for
      AUC0-24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within
      bioequivalence limits. The CYP3A5 genotype influences the dose-normalized Cmin
      with the twice-daily formulation only. CONCLUSIONS: Both tacrolimus formulations
      are bioequivalent in pediatric renal recipients. However, we observed a decrease
      in AUC0-24 and Cmin after the conversion, requiring close pharmacokinetic
      monitoring during the conversion period.

PMID- 24435760
TI  - When listening for hoofbeats, sometimes there are zebras--an interesting case of
      a teenager with edema and high blood pressure.

PMID- 24435761
TI  - Bifurcation analysis of a Morris-Lecar neuron model.
AB  - In this paper, we investigate the dynamical behaviors of a Morris-Lecar neuron
      model. By using bifurcation methods and numerical simulations, we examine the
      global structure of bifurcations of the model. Results are summarized in various
      two-parameter bifurcation diagrams with the stimulating current as the abscissa
      and the other parameter as the ordinate. We also give the one-parameter
      bifurcation diagrams and pay much attention to the emergence of periodic
      solutions and bistability. Different membrane excitability is obtained by
      bifurcation analysis and frequency-current curves. The alteration of the membrane
      properties of the Morris-Lecar neurons is discussed. 

PMID- 24435763
TI  - High level production of beta-galactosidase exhibiting excellent milk-lactose
      degradation ability from Aspergillus oryzae by codon and fermentation
      optimization.
AB  - A beta-galactosidase gene from Aspergillus oryzae was engineered utilizing codon
      usage optimization to be constitutively and highly expressed in the Pichia
      pastoris SMD1168H strain in a high-cell-density fermentation. After fermentation
      for 96 h in a 50-L fermentor using glucose and glycerol as combined carbon
      sources, the recombinant enzyme in the culture supernatant had an activity of
      4,239.07 U mL(-1) with o-nitrophenyl-beta-D-galactopyranoside as the substrate,
      and produced a total of extracellular protein content of 7.267 g L(-1) in which
      the target protein (6.24 g L(-1)) occupied approximately 86 %. The recombinant
      beta-galactosidase exhibited an excellent lactose hydrolysis ability. With 1,000
      U of the enzyme in 100 mL milk, 92.44 % lactose was degraded within 24 h at 60 
      degrees C, and the enzyme could also accomplish the hydrolysis at low
      temperatures of 37, 25, and 10  degrees C. Thus, this engineered strain had
      significantly higher fermentation level of A. oryzae lactase than that before
      optimization and the beta-galactosidase may have a good application potential in
      whey and milk industries.

PMID- 24435764
TI  - Bio-detoxification of phorbol esters and other anti-nutrients of Jatropha curcas
      seed cake by fungal cultures using solid-state fermentation.
AB  - Jatropha seed cake, a byproduct after biodiesel extraction, has several anti
      nutrients and toxins. Solid-state fermentation was carried out for the
      detoxification of the Jatropha seed cake (JSC) using different fungal cultures.
      The reduction in the anti-nutritional components such as tannins, phytates,
      saponins, lectin and protease inhibitor, and phorbol esters on 6th, 9th, and 12th
      day of fermentation was analyzed. The phorbol ester content in the unfermented
      JSC was 0.83 mg/g, and the maximum degradation of phorbol esters to the extent of
      75% was observed in the case of JSC fermented with Cunninghamella echinulata CJS
      90. The phytate degradation in the fermented JSC was in the range of 65-96%.
      There was a gradual reduction of saponin content in the JSC from 6th to 12th day,
      and the reduction of saponin was in the range of 55-99% after solid-state
      fermentation. The trypsin inhibitor activity and lectin were 1,680 trypsin
      inhibitor units (TIU) per gram and 0.32 hemagglutinating unit in the unfermented
      JSC, respectively. Trypsin inhibitor activity and lectin could not be detected in
      JSC after 12th day of solid-state fermentation. Tannins accounted for 0.53% in
      unfermented JSC, and there was a marginal increase of tannins after solid-state
      fermentation. The results indicate that biological detoxification could be a
      promising method to reduce anti-nutritional compounds and toxins in the JSC.

PMID- 24435762
TI  - Handheld optical coherence tomography during sedation in young children with
      optic pathway gliomas.
AB  - IMPORTANCE: Monitoring young children with optic pathway gliomas (OPGs) for
      visual deterioration can be difficult owing to age-related noncompliance. Optical
      coherence tomography (OCT) measures of retinal nerve fiber layer (RNFL) thickness
      have been proposed as a surrogate marker of vision but this technique is also
      limited by patient cooperation. OBJECTIVE: To determine whether measures of
      circumpapillary RNFL thickness, acquired with handheld OCT (HH-OCT) during
      sedation, can differentiate between young children with and without vision loss
      from OPGs. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis of a
      prospective observational study was conducted at a tertiary-care children's
      hospital. Children with an OPG (sporadic or secondary to neurofibromatosis type
      1) who were cooperative for visual acuity testing, but required sedation to
      complete magnetic resonance imaging, underwent HH-OCT imaging of the
      circumpapillary RNFL while sedated. MAIN OUTCOMES AND MEASURES: Area under the
      curve of the receiver operating characteristic, sensitivity, specificity,
      positive predictive value, and negative predictive value of the average and
      quadrant-specific RNFL thicknesses. RESULTS: Thirty-three children (64 eyes) met
      inclusion criteria (median age, 4.8 years; range, 1.8-12.6 years). In children
      with vision loss (abnormal visual acuity and/or visual field), RNFL thickness was
      decreased in all quadrants compared with the normal-vision group (P < .001 for
      all comparisons). Using abnormal criteria of less than 5% and less than 1%, the
      area under the curve was highest for the average RNFL thickness (0.96 and 0.97,
      respectively) compared with specific anatomic quadrants. The highest
      discrimination and predictive values were demonstrated for participants with 2 or
      more quadrants meeting less than 5% (sensitivity = 93.3; specificity = 97.9;
      positive predictive value = 93.3; and negative predictive value = 97.9) and less
      than 1% (sensitivity = 93.3; specificity = 100; positive predictive value = 100;
      and negative predictive value = 98.0) criteria. CONCLUSIONS AND RELEVANCE:
      Measures of RNFL thickness acquired with HH-OCT during sedation can differentiate
      between young children with and without vision loss from OPGs. For young children
      who do not cooperate with vision testing, HH-OCT measures may be a surrogate
      marker of vision. Longitudinal studies are needed to delineate the temporal
      relationship between RNFL decline and vision loss.

PMID- 24435765
TI  - A study of the effects of aeration and agitation on the properties and production
      of xanthan gum from crude glycerin derived from biodiesel using the response
      surface methodology.
AB  - The effects of aeration and agitation on the properties and production of xanthan
      gum from crude glycerin biodiesel (CGB) by Xanthomonas campestris
      mangiferaeindicae 2103 were investigated and optimized using a response surface
      methodology. The xanthan gum was produced from CGB in a bioreactor at 28  degrees
      C for 120 h. Optimization procedures indicated that 0.97 vvm at 497.76 rpm
      resulted in a xanthan gum production of 5.59 g L(-1) and 1.05 vvm at 484.75 rpm
      maximized the biomass to 3.26 g L(-1). Moreover, the combination of 1.05 vvm at
      499.40 rpm maximized the viscosity of xanthan at 0.5% (m/v), 25  degrees C, and
      25 s(-1) (255.40 mPa s). The other responses did not generate predictive models.
      Low agitation contributed to the increase of xanthan gum production, biomass,
      viscosity, molecular mass, and the pyruvic acid concentration. Increases in the
      agitation contributed to the formation of xanthan gum with high mannose
      concentration. Decreases in the aeration contributed to the xanthan gum
      production and the formation of biopolymer with high mannose and glucose
      concentrations. Increases in aeration contributed to increased biomass,
      viscosity, and formation of xanthan gum with greater resistance to thermal
      degradation. Overall, aeration and agitation of CGB fermentation significantly
      influenced the production of xanthan gum and its properties.

PMID- 24435766
TI  - Effect of various colors of light-emitting diodes (LEDs) on the biomass
      composition of Arthrospira platensis cultivated in semi-continuous mode.
AB  - In the present study, semi-continuous cultivation of Arthrospira platensis using
      various colors of light-emitting diodes (LEDs) as artificial lighting was
      performed in order to study their effects on the biomass composition of A.
      platensis. The lowest biomass productivity was obtained with blue LED (4.68 mg l(
      1) day(-1)), while the highest was obtained with pink and red LEDs (30.89 and
      30.69 mg l(-1) day(-1), respectively). All biomass compound contents were
      affected by the different colors studied, except that of total carotenoids. The
      lowest phycocyanin content was observed in pink LED (8.2%) while the maximum in
      blue LED (17.6 +/- 2.4%). Chlorophyll content was lowest in red LED (1.04%) and
      highest in blue LED (1.42%). The highest protein content was obtained with white
      and green LEDs (50.1 and 49.8%, respectively), while the lowest was obtained with
      blue LED (42.1%). Carbohydrate content was contrarily affected as that of
      proteins. The highest carbohydrate content was obtained in blue LED (11.3%) and
      the lowest under white and pink LEDs (8.8 and 8.8%, respectively). Lipid content
      seems to follow the same trend as that of carbohydrates; the highest lipid
      content was obtained in blue LED (6.0%), and the lowest was obtained under pink
      LED (3.8%).

PMID- 24435768
TI  - Extracurricular activity availability and participation and substance use among
      American Indian adolescents.
AB  - School-based extracurricular activity involvement has been associated with lower
      levels of substance use among adolescents from various populations; however,
      these associations have only been slightly examined among American Indian (AI)
      adolescents. Building from various theoretical perspectives, it was hypothesized
      that AI adolescents' perceived access to and the intensity (i.e., frequency) of
      participation in extracurricular activities would be associated with lower
      substance use and less engagement in risky substance use behaviors (i.e., being
      drunk or high at school, riding/driving with an intoxicated driver, and selling
      drugs). The moderating influences of sex, age, reservation residence, and
      metropolitan status also were examined. Data from the 2010 Arizona Youth Survey
      were analyzed for 5,701 8th, 10th, and 12th grade AI adolescents (49.1% female).
      The expected protective effects of extracurricular participation were
      demonstrated, such that high levels of perceived availability and intensity of
      participation consistently predicted low levels of all outcomes. Some of these
      associations were moderated by one or more demographic factors, with unique
      patterns emerging for each behavior. Ultimately, the findings suggest that AI
      adolescents benefit from the availability of extracurricular activities and
      intensity of participation in them, but the degree of the effect is contingent
      upon other individual and contextual characteristics.

PMID- 24435769
TI  - Comparison between PET template-based method and MRI-based method for cortical
      quantification of florbetapir (AV-45) uptake in vivo.
AB  - PURPOSE: Florbetapir (AV-45) has been shown to be a reliable tool for assessing
      in vivo amyloid load in patients with Alzheimer's disease from the early stages.
      However, nonspecific white matter binding has been reported in healthy subjects
      as well as in patients with Alzheimer's disease. To avoid this issue, cortical
      quantification might increase the reliability of AV-45 PET analyses. In this
      study, we compared two quantification methods for AV-45 binding, a classical
      method relying on PET template registration (route 1), and a MRI-based method
      (route 2) for cortical quantification. METHODS: We recruited 22 patients at the
      prodromal stage of Alzheimer's disease and 17 matched controls. AV-45 binding was
      assessed using both methods, and target-to-cerebellum mean global standard uptake
      values (SUVr) were obtained for each of them, together with SUVr in specific
      regions of interest. Quantification using the two routes was compared between the
      clinical groups (intragroup comparison), and between groups for each route
      (intergroup comparison). Discriminant analysis was performed. RESULTS: In the
      intragroup comparison, differences in uptake values were observed between route 1
      and route 2 in both groups. In the intergroup comparison, AV-45 uptake was higher
      in patients than controls in all regions of interest using both methods, but the
      effect size of this difference was larger using route 2. In the discriminant
      analysis, route 2 showed a higher specificity (94.1 % versus 70.6 %), despite a
      lower sensitivity (77.3 % versus 86.4 %), and D-prime values were higher for
      route 2. CONCLUSION: These findings suggest that, although both quantification
      methods enabled patients at early stages of Alzheimer's disease to be well
      discriminated from controls, PET template-based quantification seems adequate for
      clinical use, while the MRI-based cortical quantification method led to greater
      intergroup differences and may be more suitable for use in current clinical
      research.

PMID- 24435770
TI  - PET/CT assessment in follicular lymphoma using standardized criteria: central
      review in the PRIMA study.
AB  - PURPOSE: We aimed to compare the standardized central review of (18)F
      fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed
      after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles
      et al., Lancet 377:42-51, 2011; Trotman et al., J Clin Oncol 29:3194-3200, 2011)
      to scan review at local centres. METHODS: PET/CT scans were independently
      evaluated by two nuclear medicine physicians using the 2007 International
      Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579-586,
      2007; Juweid et al., J Clin Oncol 25:571-578, 2007; Shankar et al., J Nucl Med
      47:1059-1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al.,
      Leuk Lymphoma 50:1257-1260, 2009; Meignan et al., Leuk Lymphoma 51:2171-2180,
      2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824-1833, 2010). PET/CT
      status was compared with prospectively recorded patient outcomes. RESULTS:
      Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were
      recorded as positive, with a mean maximum standardized uptake value (SUVmax) of
      11.7 (range 4.6-35.6). There was no significant association between baseline
      SUVmax and progression-free survival (PFS). Sixty post-induction scans were
      interpreted using both the IHP criteria and 5PS. Post-induction PET-positive
      status failed to predict progression when applying the IHP criteria [p = 0.14;
      hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8-4.6] or 5PS with a cut
      off >=3 (p = 0.12; HR 2.0; 95% CI 0.8-4.7). However, when applying the 5PS with a
      cut-off >=4, there was a significantly inferior 42-month PFS in PET-positive
      patients of 25.0% (95% CI 3.7-55.8%) versus 61.4% (95% CI 45.4-74.1%) in PET
      negative patients (p = 0.01; HR 3.1; 95% CI 1.2-7.8). The positive predictive
      value (PPV) of post-induction PET with this liver cut-off was 75%. The 42-month
      PFS for patients remaining PET-positive by local assessment was 31.1% (95% CI
      10.2-55.0%) vs 64.6% (95% CI 47.0-77.6%) for PET-negative patients (p = 0.002; HR
      3.3; 95% CI 1.5-7.4), with a PPV of 66.7%. CONCLUSION: We confirm that FDG PET/CT
      status when applying the 5PS with a cut-off >=4 is strongly predictive of outcome
      after first-line immunochemotherapy for FL. Further efforts to refine the
      criteria for assessing minimal residual FDG uptake in FL should provide a
      reproducible platform for response assessment in future prospective studies of a
      PET-adapted approach.

PMID- 24435771
TI  - Joint SNMMI and EANM guideline for small-bowel and colon transit: an important
      step towards long-awaited standardization.

PMID- 24435772
TI  - Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the
      extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma.
AB  - PURPOSE: The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the
      extracellular matrix of tumours and on newly formed blood vessels and is thus a
      valuable target for radionuclide therapy. Tenarad is a fully human miniantibody
      or small immunoprotein (SIP, molecular weight 80 kDa) labelled with (131)I that
      is derived from a TC-A1-binding antibody. Previous phase I/II studies with a
      similar compound ((131)I-L19SIP) used for radioimmunotherapy (RIT) have shown
      preliminary efficacy in a variety of cancer types. In this ongoing phase I/II
      trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma
      (HL) refractory to conventional treatments. METHODS: Eight patients (four men,
      four women; age range 19 - 41) were enrolled between April 2010 and March 2011.
      All patients had received a median of three previous lines of chemotherapy (range
      three to six) and seven had also undergone autologous stem cell transplantation
      (ASCT) or bone marrow transplantation. In addition, seven patients received
      external beam radiation. All patients had nodal disease, constitutional B
      symptoms and some showed extranodal disease in skeletal bone (four patients),
      lung (three), liver (two) and spleen (one). Baseline assessments included whole
      body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT
      studies. Patients were considered eligible to receive a therapeutic dose of
      Tenarad (2.05 GBq/m(2)) if tumour uptake was more than four times higher than
      that of muscle. RESULTS: All patients were eligible and received the therapeutic
      dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and
      leucocytopenia, requiring hospitalization and therapeutic intervention. All other
      patients had haematological toxicity of grade 3 or lower, which resolved
      spontaneously. At the first response assessment (4 - 6 weeks after therapy), one
      patient showed a complete response, one showed a partial response (PR) and five
      had disease stabilization (SD). Five patients were given up to three repeated
      Tenarad treatments. One patient showed SD which then improved to a PR, three
      showed clinical benefit while maintaining SD and one patient showed disease
      progression. CONCLUSION: Tenarad RIT is effective in chemorefractory HL and
      resulted in objective responses or clinical benefit in the majority of patients.
      Toxicity was acceptable despite the high load of prior treatments, previous ASCT
      and multiple Tenarad administrations. Further studies are planned to define the
      most effective schedule for this type of RIT in HL patients.

PMID- 24435773
TI  - Role of 68Ga-DOTATOC PET/CT in initial evaluation of patients with suspected
      bronchopulmonary carcinoid.
AB  - PURPOSE: The objective of this study was to evaluate the role of (68)Ga-DOTATOC
      positron emission tomography (PET)/CT scan in patients with suspected pulmonary
      carcinoid tumour and to compare its results with (18)F-fluorodeoxyglucose (FDG)
      PET/CT scan. METHODS: In this prospective study, 32 patients (age 34.22 +/- 12.03
      years; 53.1 % female) with clinical suspicion of bronchopulmonary carcinoid were
      evaluated with (68)Ga-DOTATOC PET/CT and (18)F-FDG PET/CT. The two imaging
      modalities were compared, considering the tissue diagnosis as the reference
      standard. RESULTS: Based on the reference standard 26 cases were carcinoid
      tumours [21 typical carcinoids (TC) and 5 atypical carcinoids (AC)] and 6 cases
      were non-carcinoid tumours. The sensitivity, specificity and accuracy of (68)Ga
      DOTATOC PET/CT in the diagnosis of pulmonary carcinoid tumour were 96.15, 100 and
      96.87 % respectively, whereas those of (18)F-FDG PET/CT were 78.26, 11.1 and
      59.37 % respectively. The maximum standardised uptake value (SUV max) of TC on
      (68)Ga-DOTATOC PET/CT scan ranged from 3.58 to 55, while that of AC ranged from
      1.1 to 32.5. (18)F-FDG PET/CT was true-positive in all cases of AC and false
      negative in eight cases of TC (sensitivity for TC 61.9 % and for AC 100 %).
      CONCLUSION: (68)Ga-DOTATOC PET/CT is a useful imaging investigation for the
      evaluation of pulmonary carcinoids. (18)F-FDG PET/CT scan suffers from low
      sensitivity and specificity in differentiating the pulmonary carcinoids from
      other tumours.

PMID- 24435774
TI  - Comment on: FDG PET in the early diagnosis of large-vessel vasculitis.

PMID- 24435775
TI  - Diagnostic accuracy of 18F-FDG PET/CT for detection of suspected recurrence in
      patients with oesophageal carcinoma.
AB  - PURPOSE: To evaluate the role of (18)F-FDG PET/CT in the detection of recurrence
      in patients with oesophageal carcinoma, suspected clinically or following
      conventional investigations. METHODS: This was a retrospective study. Data from
      180 patients (age 56.3 +/- 10.4 years; 126 men, 54 women) with
      histopathologically proven oesophageal carcinoma (squamous cell 115,
      adenocarcinoma 59, neuroendocrine carcinoma 4, small cell 1, poorly
      differentiated 1) who had undergone 227 (18)F-FDG PET/CT studies for suspected
      recurrence were analysed. Recurrence was suspected clinically or following
      conventional investigations. PET/CT images were revaluated by two nuclear
      medicine physicians in consensus. Findings were grouped into local, nodal and
      distant recurrence. Results were compared to those from contrast-enhanced (CE) CT
      when available (109 patients). Clinical/imaging follow-up (minimum 6 months) with
      histopathology (when available) was taken as the reference standard. RESULTS: Of
      the 227 (18)F-FDG PET/CT studies,166 were positive and 61 were negative for
      recurrent disease. PET/CT showed local recurrence in 134, nodal recurrence in 115
      and distant recurrence in 47, with more than one site of recurrence in 34. The
      PET/CT findings were true-positive in 153 studies, true-negative in 54, false
      positive in 13 and false-negative in 7. The sensitivity of (18)F-FDG PET/CT was
      96%, the specificity was 81%, the positive and negative predictive values were
      92% and 89%, respectively, and the accuracy was 91%. PET/CT showed similar
      accuracy in patients with squamous cell carcinoma and in those with
      adenocarcinoma (P = 0.181).(18)F-FDG PET/CT was more specific than CECT (67% vs.
      21%; P < 0.0001). PET/CT was superior to CECT for the detection of nodal
      recurrence (P < 0.0001), but not local recurrence (P = 0.093) or distant
      metastases (P = 0.441). CONCLUSION: (18)F-FDG PET/CT shows high accuracy in the
      detection of suspected recurrence in patients with oesophageal carcinoma. It is
      more specific than and is superior to CECT in the detection of nodal recurrence.

PMID- 24435776
TI  - The prevalence of polycystic ovary syndrome in a normal population according to
      the Rotterdam criteria versus revised criteria including anti-Mullerian hormone.
AB  - STUDY QUESTION: What is the prevalence in a normal population of polycystic ovary
      syndrome (PCOS) according to the Rotterdam criteria versus revised criteria
      including anti-Mullerian hormone (AMH)? SUMMARY ANSWER: The prevalence of PCOS
      was 16.6% according to the Rotterdam criteria. When replacing the criterion for
      polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the
      prevalence of PCOS was 6.3 and 8.5%, respectively. WHAT IS KNOWN ALREADY?: The
      Rotterdam criteria state that two out of the following three criteria should be
      present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical
      hyperandrogenism and polycystic ovaries (AFC >= 12 and/or ovarian volume >10 ml).
      However, with the advances in sonography, the relevance of the AFC threshold in
      the definition of polycystic ovaries has been challenged, and AMH has been
      proposed as a marker of polycystic ovaries in PCOS. STUDY DESIGN, SIZE, DURATION:
      From 2008 to 2010, a prospective, cross-sectional study was performed including
      863 women aged 20-40 years and employed at Copenhagen University Hospital,
      Rigshospitalet, Denmark. PARTICIPANTS/MATERIAL, SETTING, METHODS: We studied a
      subgroup of 447 women with a mean (+/-SD) age of 33.5 (+/-4.0) years who were all
      non-users of hormonal contraception. Data on menstrual cycle disorder and the
      presence of hirsutism were obtained. On cycle Days 2-5, or on a random day in the
      case of oligo- or amenorrhoea, sonographic and endocrine parameters were
      measured. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of PCOS was 16.6%
      according to the Rotterdam criteria. PCOS prevalence significantly decreased with
      age from 33.3% in women < 30 years to 14.7% in women aged 30-34 years, and 10.2%
      in women >= 35 years (P < 0.001). In total, 53.5% fulfilled the criterion for
      polycystic ovaries with a significant age-related decrease from 69.0% in women <
      30 years to 55.8% in women aged 30-34 years, and 42.8% in women >= 35 years (P <
      0.001). AMH or age-adjusted AMH Z-score was found to be a reliable marker of
      polycystic ovaries in women with PCOS according to the Rotterdam criteria [area
      under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990-0.999] and AUC
      0.992 (95% CI: 0.987-0.998), respectively], and an AMH cut-off value of 18 pmol/l
      and AMH Z-score of -0.2 showed the best compromise between sensitivity (91.8 and
      90.4%, respectively) and specificity (98.1 and 97.9%, respectively). In total,
      AFC > 19 or AMH > 35 occurred in 17.7 and 23.0%, respectively. The occurrence of
      AFC > 19 or AMH > 35 in the age groups < 30, 30-34 and >= 35 years was 31.0 and
      35.7%, 18.8 and 21.3%, and 9.6 and 18.7%, respectively. When replacing the
      Rotterdam criterion for polycystic ovaries by AFC > 19 or AMH > 35 pmol/l, the
      prevalence of PCOS was 6.3 or 8.5%, respectively, and in the age groups < 30, 30
      34 and >= 35 years, the prevalences were 17.9 and 22.6%, 3.6 and 5.6%, and 3.6
      and 4.8%, respectively. LIMITATIONS, REASON FOR CAUTION: The participants of the
      study were all health-care workers, which may be a source of selection bias.
      Furthermore, the exclusion of hormonal contraceptive users from the study
      population may have biased the results, potentially excluding women with symptoms
      of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: AMH may be used as a marker of
      polycystic ovaries in PCOS. However, future studies are needed to validate AMH
      threshold levels, and AMH Z-score may be appropriate to adjust for the age
      related decline in the AFC. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 24435777
TI  - Sexual orientation of women does not affect outcome of fertility treatment with
      donated sperm.
AB  - STUDY QUESTION: Is there a difference in fertility between heterosexual women and
      lesbians undergoing sperm donation? SUMMARY ANSWER: Women undergoing treatment
      with donated sperm are equally fertile regardless of sexual orientation. WHAT IS
      KNOWN ALREADY: Lesbians have an increased prevalence of smoking, obesity,
      sexually transmitted diseases and, possibly, polycystic ovary syndrome, all
      factors known to affect fertility. Previous studies on sperm donation
      inseminations (D-IUI) show conflicting results regarding pregnancy outcome. STUDY
      DESIGN, SIZE, DURATION: This is a national study of 171 lesbians and 124
      heterosexual women undergoing sperm donation both as D-IUI (lesbian n = 438,
      heterosexual n = 298) and as embryo transfers (ET) after IVF with donated sperm
      (lesbians n = 225, heterosexuals n = 230) during 2005-2010.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: All clinics in Sweden offering sperm
      donation recruited patients. Differences in patients' medical history, treatment
      results and number of treatments to live birth were analyzed using independent
      samples t-test, Pearson's chi(2) test or Fisher's exact probability test. MAIN
      RESULTS AND THE ROLE OF CHANCE: 71.8% of heterosexuals and 69.0% of lesbians had
      a child after treatment. The mean number of treatments was 4.2 for heterosexual
      women and 3.9 for lesbians. The total live birth rate, regardless of treatment
      type, was 19.7% for heterosexuals and 19.5% for lesbians. For D-IUI, the live
      birth rate was 12.8% for heterosexuals and 16.0% for lesbians and the live birth
      rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7% for
      heterosexuals and 26.2% for lesbians. There were no differences in live birth
      rate between the groups for each of the different types of insemination
      stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH
      combined). Nor was there a difference in live birth rate between the groups for
      either fresh or thawed embryo transfer. There was no difference between the
      proportions of women in either group or the number of treatments needed to
      achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2%),
      uterine polyps (7.2%) or previous children (11.3%) than lesbians (smokers 2.8%, P
      = 0.03; polyps 1.8%, P = 0.03; child 2.5%, P = 0.003). LIMITATIONS, REASONS FOR
      CAUTION: This study is limited to women living in stable relationships undergoing
      treatment with donated sperm in a clinical setting and may not apply to single
      women or those undergoing home inseminations. WIDER IMPLICATIONS OF THE FINDINGS:
      These results may influence healthcare policy decisions as well as increase the
      quality of clinical care and medical knowledge of healthcare professionals. The
      data also have important implications for individuals regarding screening,
      infertility diagnostic procedures and treatment types offered to heterosexuals
      and lesbians seeking pregnancy through sperm donation. STUDY FUNDING/COMPETING
      INTEREST(S): Funding was granted by the Stiftelsen Familjeplaneringsfonden i
      Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and
      the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of
      interest.

PMID- 24435778
TI  - ESHRE guideline: management of women with endometriosis.
AB  - STUDY QUESTION: What is the optimal management of women with endometriosis based
      on the best available evidence in the literature? SUMMARY ANSWER: Using the
      structured methodology of the Manual for ESHRE Guideline Development, 83
      recommendations were formulated that answered the 22 key questions on optimal
      management of women with endometriosis. WHAT IS KNOWN ALREADY: The European
      Society of Human Reproduction and Embryology (ESHRE) guideline for the diagnosis
      and treatment of endometriosis (2005) has been a reference point for best
      clinical care in endometriosis for years, but this guideline was in need of
      updating. STUDY DESIGN, SIZE, DURATION: This guideline was produced by a group of
      experts in the field using the methodology of the Manual for ESHRE Guideline
      Development, including a thorough systematic search of the literature, quality
      assessment of the included papers up to January 2012 and consensus within the
      guideline group on all recommendations. To ensure input from women with
      endometriosis, a patient representative was part of the guideline development
      group. In addition, patient and additional clinical input was collected during
      the scoping and review phase of the guideline. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: NA. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 83
      recommendations on diagnosis of endometriosis and on the treatment of
      endometriosis-associated pain and infertility, on the management of women in whom
      the disease is found incidentally (without pain or infertility), on prevention of
      recurrence of disease and/or painful symptoms, on treatment of menopausal
      symptoms in patients with a history of endometriosis and on the possible
      association of endometriosis and malignancy. LIMITATIONS, REASONS FOR CAUTION: We
      identified several areas in care of women with endometriosis for which robust
      evidence is lacking. These areas were addressed by formulating good practice
      points (GPP), based on the expert opinion of the guideline group members. WIDER
      IMPLICATIONS OF THE FINDINGS: Since 32 out of the 83 recommendations for the
      management of women with endometriosis could not be based on high level evidence
      and therefore were GPP, the guideline group formulated research recommendations
      to guide future research with the aim of increasing the body of evidence. STUDY
      FUNDING/COMPETING INTEREST(S): The guideline was developed and funded by ESHRE,
      covering expenses associated with the guideline meetings, with the literature
      searches and with the implementation of the guideline. The guideline group
      members did not receive payment. All guideline group members disclosed any
      relevant conflicts of interest (see Conflicts of interest). TRIAL REGISTRATION
      NUMBER: NA.

PMID- 24435779
TI  - Anti-Mullerian hormone is a more accurate predictor of individual time to
      menopause than mother's age at menopause.
AB  - STUDY QUESTION: In the prediction of time to menopause (TTM), what is the added
      value of anti-Mullerian hormone (AMH) when mother's age at natural menopause
      (ANM) is also known? SUMMARY ANSWER: AMH is a more accurate predictor of
      individual TTM than mother's age at menopause. WHAT IS KNOWN ALREADY: Mother's
      ANM is considered a proxy for daughter's ANM although studies on its predictive
      accuracy are non-existent. AMH is a biomarker with a known capacity to predict
      ANM. However, its added value on top of known predictors, like mother's ANM, is
      unknown. STUDY DESIGN, SIZE, DURATION: Population-based cohort studies were used.
      To assess any additive predictive value of mother's ANM, 164 mother-daughter
      pairs were used (Group 1). To assess the added value of AMH, a second group of
      150 women in whom AMH and mother's ANM were recorded prior to a 12-year follow-up
      period during which daughter's ANM was assessed was used (Group 2).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Group 1 consisted of participants of
      the DOM cohort (an ongoing breast cancer study). Group 2 was a pooled cohort of
      women with regular menstrual cycles from two independent published studies. Cox
      proportional hazards analysis estimated uni- and multivariate regression
      coefficients for female age at study entry, mother's ANM and AMH in the
      prediction of TTM. Discrimination of models was assessed with C-statistics.
      Clinical added value of AMH was quantified with a net reclassification index
      (NRI). MAIN RESULTS AND THE ROLE OF CHANCE: A model with female age and mother's
      ANM had a c-statistic of 79 and 85% in groups 1 and 2, respectively. Both age and
      mother's ANM were significantly associated with TTM (HR 1.54 and HR 0.93 for age
      and mother's ANM in Cohort 1 and HR 1.59 and HR 0.89 in Group 2, respectively. P
      value for all <0.001). In Group 2, the multivariate model with age, mother's ANM
      and AMH had a c-statistic of 92%, and only female age and AMH remained
      significantly associated with TTM (HR 1.41 P < 0.0001; HR 0.93 P = 0.08 and HR
      0.06 P < 0.0001 for age, mother's ANM and AMH, respectively). The mean weighted
      NRI suggests that a 47% improvement in predictive accuracy is offered by adding
      AMH to the model of age and mother's ANM. In conclusion, AMH and mother's ANM
      both have added value in forecasting TTM for the daughter based on her age. In
      comparison, AMH is a more accurate added predictor of TTM than mother's ANM.
      LIMITATIONS, REASONS FOR CAUTION: The cohort of women is relatively small and
      different cohorts of women were pooled. WIDER IMPLICATIONS OF THE FINDINGS: This
      study shows that AMH is a more accurate predictor of ANM than mother's ANM.
      However, before achieving clinical applicability, the certainty with which a
      woman's prediction is made must improve. The association between mother's ANM and
      TTM in daughters did not appear to be influenced by whether ANM was recorded by
      mothers or daughters--an important finding because in the clinical setting
      daughters usually provide this information. STUDY FUNDING/COMPETING INTEREST(S):
      No funding was received and there were no competing interests in direct relation
      to this study.

PMID- 24435780
TI  - Energy transfer and pigment composition in three chlorophyll b-containing light
      harvesting complexes isolated from Mantoniella squamata (Prasinophyceae),
      Chlorella fusca (Chlorophyceae) and Sinapis alba.
AB  - Light-harvesting Chl a/b protein complexes were isolated from the higher plant
      Sinapis alba, the green alga Chlorella fusca, and the prasinophycean alga
      Mantoniella squamata by mild gel electrophoresis. The energy transfer from
      chlorophyll b and the accessory xanthophyll was measured by means of fluoresence
      spectroscopy at 77 K. The pigment composition of the isolated antenna complexes
      was determined by high performance liquid chromatography in order to calculate
      the number of light absorbing molecules per chlorophyll a in the different light
      harvesting complexes. These results were complemented by the quantitation of the
      pigments in total thylakoids as well as in the different electrophoretic
      fractions. On the basis of these data the in vivo ratios of xanthophylls per
      chlorophyll a could be estimated. The results show that the light-harvesting
      complexes from Chlorella and from Sinapis exhibit identical ratios of total
      xanthophylls per chlorophyll a. By contrast, in the prasinophycean alga
      Mantoniella, the light-harvesting complex markedly differs from the other
      chlorophyll b containing proteins. It contains, in addition to neoxanthin and
      violaxanthin, high amounts of prasinoxanthin and its epoxide, which contribute
      significantly to light absorption. The concentration of chlorophyll b in the
      complex is very much higher in the antenna of Mantoniella than in those of
      Chlorella and Sinapis. Furthermore, it must be emphasized that in addition to
      chlorophyll b, a third chlorophyll species acts in the energy transfer to
      chlorophyll a. This chlorophyll c-like pigment is found to be present in a
      concentration which improves very efficiently the absorption in blue light. In
      light of these results it can be concluded that the absorption cross section in
      Mantoniella is higher not only because of an enhanced number of light-harvesting
      particles in the membrane, but also because of a higher ratio of accessory
      pigments to chlorophyll a. 

PMID- 24435781
TI  - Gas exchange of two CAM species of the genus Cissus (vitaceae) differing in
      morphological features.
AB  - Pattern and magnitude of stem gas exchange were studied under controlled
      conditions on two CAM species of the genus Cissus differing in morphological
      features. In the cactus-like liana Cissus quadrangularis, at water vapour deficit
      of the air (VPD) lower than 400 mPa Pa(-1) during daytime, under 24/16 degrees C
      and 27/16 degrees C temperature regime, CO2 uptake occurred during daytime and
      nighttime but night fixation was responsible for 74 and 77% respectively of the
      CO2 fixed during the whole diurnal cycle; the contribution of night fixation
      increased up to 84% at VPD of 590 mPa Pa(-1) under 27/15 degrees C. In Cissus
      sp., a slightly succulent xerophytic liana with mesophytic deciduous leaves, at
      27 degrees C day temperature and VPD of 520-540 mPa Pa(-1), under both 12 and 16
      degrees C night temperature, CO2 uptake occurred exclusively during the night;
      however at lower day temperatures (18-20 degrees C) and lower VPD (169-269 mPa
      Pa(-1)) substantial CO2 uptake was observed in the light. Transpiration was
      higher in Cissus sp. than in Cissus quadrangularis under all of the conditions
      applied; moreover night transpiration in Cissus sp. contributed more to total day
      transpiration as compared with Cissus quadrangularis. The results support the
      opinion that the nocturnal gas exchange has a preeminent role in Cissus sp. as
      compared with Cissus quadrangularis. Indeed under conditions which enhance
      evaporative demand even well-watered plants of Cissus sp. resort totally to night
      fixation. In contrast Cissus quadrangularis which shows a larger resistance to
      water loss and possesses an abundant water storing parenchyma as compared with
      Cissus sp. resorts totally to night CO2 fixation only under drought stress. 

PMID- 24435782
TI  - Time-resolved chlorophyll fluorescence studies on photosynthetic mutants of
      Chlamydomonas reinhardtii: origin of the kinetic decay components.
AB  - The room temperature chlorophyll fluorescence decay kinetics of photosynthetic
      mutants of Chlamydomonas reinhardtii have been measured as a function of
      Photosystem 2 (PS2) trap closure, DNB-induced quenching at FM, and time-resolved
      emission spectra. The overall decays have been analyzed in terms of three or four
      kinetic components where necessary. A comparison of the characteristics of the
      decay components exhibited by the mutants with the wild-type has been carried out
      to elucidate the precise origins of the different emissions in relation to the
      observed pigment-protein complexes. It is shown that a) charge recombination in
      PS2 is not necessary for the presence of long-lived decay components, b) there
      are two rapid PS1-associated emissions (tau=30 and 150-200 ps), c) a slow PS1
      decay is observed (tau=1.73 ns) in the absence of PS1 reaction centres, d) the
      two variable components (tau=0.25-1.2 and 0.5-2.2 ns) observed in the wild-type
      arise from LHC2 and e) a rapid (tau=50-250 ps) decay is associated with the PS2
      core antenna (CP3 and CP4). These results show that the intact thylakoid membrane
      system is too complex to distinguish all of the individual kinetic components. 

PMID- 24435783
TI  - Membrane charge affecting electron donation to PS II in chloroplasts.
AB  - Pretreatment of chloroplast with 0.75 mM of EDTA inhibits markedly electron flow
      at pH above 8.5. This inhibition can be reversed by adding donors to PS II or by
      addition of salts to the reaction medium.Restoration of electron flow in EDTA
      treated chloroplasts by salts depends clearly on the valency of the cation used.
      The efficiency observed is: C(3+)>C(2+)>C(+), which is indicative of screening of
      negative charges on the membrane. However, maximal restoration of electron flow
      depends also on the presence of a relatively low concentration of Cl(-) which is
      known to be required at the oxygen evolution site. Charge density in the region
      of Q was measured in control and EDTA-treated chloroplasts. The calculated charge
      densities were: -1.1 MUC/cm(2) and -2.0 MUC/cm(2) for control and EDTA-treated
      chloroplasts respectively.It is concluded that EDTA-treatment, by dissipating 
      degrees  pH and by chelating Mg(2+), causes an increase in the negative charge
      density on the thylakoid membrane which includes a site (or sites) closely
      related to water donation. 

PMID- 24435784
TI  - Development of photosynthetic electron transport reactions under the influence of
      phytohormones and nitrate nutrition in greening cucumber cotyledons.
AB  - Development of the photosynthetic electron transport system, under the influence
      of hormones and nitrate-nutrition, in greening cucumber cotyledon was
      investigated. Both photosystems, PS I measured as DCPIP -> MV, and PS II as H2O 
      > pBQ, were significantly promoted by GA and kinetin with kinetin being more
      effective. PS II/PS I ratio, though increased in control, did not change
      significantly with GA or kinetin treatment. Other partial reactions (H2O ->
      MV/K3Fe(CN)6/NADP) were also promoted. Addition of KNO3 showed concentration
      dependent effects on growth and photosynthetic electron transport reactions (H2O 
      > MV/K3Fe(CN)6/NADP). It is concluded that both hormones and nutritional status
      influence development of the photosynthetic electron transport system in greening
      cucumber cotyledons. 

PMID- 24435785
TI  - Studies on the protolytic reactions coupled with water cleavage in photosystem II
      membrane fragments from spinach.
AB  - The protolytic reactions of PSII membrane fragments were analyzed by measurements
      of absorption changes of the water soluble indicator dye bromocresol purple
      induced by a train of 10 MUs flashes in dark-adapted samples. It was found that:
      a) in the first flash a rapid H(+)-release takes place followed by a slower H(+)
      uptake. The deprotonation is insensitive to DCMU but is completely eliminated by
      linolenic acid treatment of the samples; b) the extent of the H(+)-uptake in the
      first flash depends on the redox potential of the suspension. In this time domain
      no H(+)-uptake is observed in the subsequent flashes; c) the extent of the H(+)
      release as a function of the flash number in the sequence exhibits a
      characteristic oscillation pattern. Multiphasic release kinetics are observed.
      The oscillation pattern can be satisfactorily described by a 1, 0, 1, 2
      stoichiometry for the redox transitions Si -> Si+1 (i=0, 1, 2, 3) in the water
      oxidizing enzyme system Y. The H(+)-uptake after the first flash is assumed to be
      a consequence of the very fast reduction of oxidized Q400(Fe(3+)) formed due to
      dark incubation with K3[Fe(CN)6]. The possible participation of component Z in
      the deprotonation reactions at the PSII donor side is discussed. 

PMID- 24435786
TI  - Investigation of the spatial relationships between photosystem 2 polypeptides by
      reversible crosslinking and diagonal electrophoresis.
AB  - Nearest neighbour relationships within the LHC2-PS2 complex were investigated by
      using the reversible crosslinking agent dithiobis(succinimidyl propionate) (DSP).
      This was accomplished by treating PS2-enriched membranes, prepared from
      chloroplasts of Pisum sativum, with the crosslinker followed by diagonal
      electrophoresis of the solubilised polypeptides.Analysis of the off-diagonal spot
      patterns produced by crosslinker cleavage and second dimension electrophoresis
      was made on the basis of: staining with Coomassie blue or silver, labelling with
      [(35)S]-methionine, and sensitivity to 1 M NaCl washing. It was concluded that
      LHC2 polypeptides crosslinked with several components of the PS2 complex and that
      the extrinsic polypeptides associated with water oxidation, having approximate
      molecular weights of 16 and 23 kDa, crosslink to form homodimers. The latter
      finding suggests that there may be more than one copy of each of these
      polypeptides per PS2 complex. 

PMID- 24435787
TI  - Cystic fibrosis as a rare cause of apple peel syndrome.
AB  - Apple peel atresia is a special form of intestinal atresia with absence of
      mesentery. It is most likely due to an intrauterine intestinal vascular accident
      and has been described with other anomalies. Meconium ileus can compromise blood
      supply causing intestinal atresia. Therefore, cystic fibrosis needs to be ruled
      out in apple peel syndrome. 

PMID- 24435788
TI  - Nasogastric vs. intravenous rehydration in children with gastroenteritis and
      refusal to drink: a randomized controlled trial.
AB  - BACKGROUND: Nasogastric rehydration therapy (NGRT) is the recommended therapy in
      moderately dehydrated children with gastroenteritis and refusal to drink, since
      it is supposed to be as effective if not better than intravenous rehydration
      therapy (IVRT). However, in clinical practice IVRT is often favored. We conducted
      a clinical trial to determine whether IVRT is not inferior to NGRT. PATIENTS AND
      METHODS: Children 3 months to 6 years of age with moderate dehydration and
      refusal to drink secondary to gastroenteritis were recruited. After clinical
      assessment of the degree of dehydration, patients were assigned randomly to
      receive either IVRT or NGRT over 6 h on the hospital ward. RESULTS: Recruitment
      did not yield the estimated number of patients. Mainly, non-enrollment was due to
      failure to obtain parental consent because IVRT was expected. 97 patients were
      enrolled in the study, 46 were randomized to NGRT and 51 to IVRT. There was no
      difference between IVRT and NGRT groups concerning length of hospital stay (2.2+/
      1.1 days vs. 2.4+/-1.1 days), success of rehydration (78 vs. 76%) and adverse
      events. DISCUSSION: Since we had to terminate the study ahead of schedule due to
      a low recruiting rate, our results are not reliable. However, data from the
      literature shows that the widespread described superiority of NGRT over IVRT is
      seriously influenced by studies from developing countries questioning the
      applicability of the results to a setting available in high-income countries
      nowadays. CONCLUSION: Our study demonstrates the difficulties performing such a
      study in a high-income country to come to an objective and clearly evident final
      conclusion.

PMID- 24435789
TI  - Compliance with guidelines recommending the use of simulation for neonatal and
      infant resuscitation training in Austria.
AB  - BACKGROUND: Current international resuscitation guidelines recommend simulation
      for the training of neonatal and infant resuscitation. We aimed at assessing
      compliance rates with these recommendations in Austria. METHOD: We performed a
      national questionnaire survey among 31 neonatal institutions in Austria. RESULTS:
      25 questionnaires (80.6%) were analyzed. 22/25 institutions (88%) used simulation
      as an instructional modality. 8 institutions (32%) had access to medical
      simulation centers, with 6/8 being used for neonatal and infant resuscitation
      training. Simulation equipment was available at 17/25 institutions (68%), with a
      median of 1 part-task trainer (0-2), 2 low-fidelity resuscitation mannequins (0
      10), and 0 high-fidelity patient simulators (0-7). Resuscitation training
      frequency varied widely, ranging from one training per month to one training per
      year. 5 simulation centers utilized interdisciplinary resuscitation training with
      other medical specialties and team training including physicians and nursing
      staff. Of the 17 institutions with simulation equipment at their disposal, 8
      (47.1%) carried out interdisciplinary training and 13 (76.5%) performed team
      oriented training sessions. DISCUSSION/CONCLUSION: The majority of surveyed
      institutions adopted simulation for neonatal and infant resuscitation training
      according to current guidelines and had simulation equipment at their disposal.
      However, educational practice varied widely, especially in regard to training
      frequency. Therefore, we suggest a national consensus agreement on best practices
      in simulation-based neonatal and infant resuscitation training.

PMID- 24435790
TI  - [Measles epidemic in a highly developed country: low mortality, high morbidity
      and extensive costs].
AB  - BACKGROUND: Vaccination with 2 doses of > 95% of the population is necessary to
      eliminate measles. In Switzerland and especially in the central part, vaccine
      coverage is low (2006: 65%). This led 2006-2009 to a measles epidemic with
      thousands of cases and high costs. One death was noted in a formerly healthy 12
      year old girl. PATIENTS AND METHODS: All measles cases, either hospitalized or
      reported to the authority, in the canton Lucerne between 2006 and 2009 were
      included. Course, complications, immunization rates and costs of the hospitalized
      children were analyzed. RESULTS: A total of 1 041 cases of measles were recorded;
      758 (73%) were children < 16 years of age. 56 (6%) of the patients were admitted
      to hospital; half of them were children (n=26, admission rate 3.4%). Main
      complications were pneumonia with oxygen requirement (n=19), bacterial infections
      of the base of the skull (n=2) and acute measles encephalitis (n=3). One child
      each developed acute appendicitis and diabetes mellitus type 1. No death was
      noted. Median hospitalisation costs were 18 780 CHF. The surveillance system was
      incomplete: Every third admitted child was not reported to the authority.
      CONCLUSION: Due to low vaccine coverage measles still account for epidemics with
      high morbidity and extensive costs. Instant reporting of all cases is crucial for
      disease control. Early identification of persons at risk allows timely
      immunization. Switzerland will remain of central importance to eliminate measles
      in Europe by 2015.

PMID- 24435791
TI  - Blood transfusions using 27 gauge PICC lines: a retrospective clinical study on
      safety and feasibility.
AB  - BACKGROUND: Blood transfusions are required by most extremely low birth weight
      (ELBW) infants, but sometimes an adequate peripheral venous access cannot be
      achieved. Under these circumstances, we used 27 Gauge (G) peripherally inserted
      central catheter (PICC) lines that are routinely inserted on the second day of
      life. Due to their narrow lumen, hemolysis of transfused erythrocytes was a major
      concern. We therefore performed a retrospective study in ELBW infants to analyze
      the incidence, safety and feasibility of PRBC transfusions via 27 G PICC lines.
      METHODS: ELBW infants admitted from 08/2011-07/2012 were screened for packed red
      blood cell (PRBC) transfusions. Those applied via 27 G PICC lines were
      identified. For analysis of transfusion safety (hemolysis), hemoglobin and
      potassium levels as well as cardiovascular variables (invasive mean arterial
      blood pressure and heart rate) were evaluated before and after transfusion. For
      analysis of transfusion feasibility, catheter removal after transfusion and the
      reason for removal were recorded. RESULTS: A total of 648 transfusions were
      applied in 110 ELBW infants. 27 infants (24%) received no transfusion. In 12/83
      (14.5%) infants who received PRBCs, transfusions were applied using a 27 G PICC
      line (38/648, 5.9%). Patients who received PRBCs via the PICC line were smaller
      at birth (582 g [range 380-752 g] vs. 710 g [430-972 g]; 23+6 [23+1-27+6] vs.
      26+0 [23+1-31+4]) and required a higher number of PRBC transfusions (n=13 vs.
      n=5) overall. Transfusion analysis showed an appropriate increase of blood
      hemoglobin levels and stable potassium levels as well as cardiovascular
      parameters. 4/38 of PICC lines were removed within 24 h after transfusion, one
      due to occlusion (15 h after transfusion). CONCLUSIONS: We conclude that PRBC
      transfusions via 27 G PICC lines were feasible and performed without signs of
      hemolysis in ELBW infants. Our findings may help clinicians in the management of
      ELBW infants requiring transfusions if a peripheral venous access is not
      achievable.

PMID- 24435792
TI  - [Treatment of neonatal asphyxia with a special focus on therapeutic hypothermia].
AB  - In recent years the treatment of newborns for neonatal asphyxia has experienced a
      lot of new developments. A major milestone were the positive results of various
      trials for prophylactic treatment of hypoxic-ischemic encephalopathy by moderate
      cooling of the child or of his head. With this paper we attempt to provide a
      consented guideline to aid in the treatment decision for affected newborns and
      thus achieve a more homogeneous treatment strategy throughout Germany. 

PMID- 24435793
TI  - Emergency out-of-hospital presentation of neonatal esophageal atresia with
      tracheoesophageal fistula.

PMID- 24435794
TI  - Mobile proton triggered radical fragmentation of nitroarginine containing
      peptides.
AB  - Protonated nitroarginine, [R(NO2) + H](+), which contains the nitroguanidine
      'explosophore,' undergoes homolytic N - N nitro-imine bond cleavage to expel
      NO2(*) and form a radical cation of arginine in high yield (100% relative
      abundance) upon low-energy collision-induced dissociation (CID). Other ionization
      states of nitroarginine, including [R(NO2) - H](-), and a fixed-charge derivative
      of nitroarginine do not expel NO2(*) (<1%), but instead dissociate via
      heterolytic bond cleavage with abundant losses of small molecules (N2O and
      H2N2O2) from the nitroguanidine group. The effects of proton mobility on the CID
      reactions of nitroarginine containing peptides was investigated for peptide
      derivatives of leucine enkephalin, including XYGGFLR(NO2), X = D, G, K, and R, by
      examining the different protonation states: [M - H](-); [M + H](+); and [M +
      2H](2+). For [M + H](+) containing the less basic N-terminal residues (X = D, G)
      and all [M + 2H](2+), mobile proton fragmentation reactions that result in
      peptide sequence ions dominate. In contrast, for peptides containing the basic N
      terminal residues (R and K), the CID spectra of both the [M - H](-) and [M +
      H](+) are dominated by the losses of small even-electron neutrals from the
      nitroarginine side-chain. The fraction of nitroguanidine directed fragmentation
      of the nitroarginine side chain that results in bond homolysis to form
      [XYGGFLR](+*) by expulsion of NO2(*) increases by more than 10 times as the
      protonation state changes from [M - H](-) (<10%) to [M + 2H](2+) (ca. 90%) and by
      about four times as the acidity of the [M + H](+) N-terminal residue increases
      from R (19.0%) to D (76.5%). These results indicate that protonated peptides
      containing nitroarginine can undergo non-canonical mobile proton triggered
      radical fragmentation.

PMID- 24435795
TI  - Host-guest chemistry in the gas phase: complex formation of cucurbit[6]uril with
      proton-bound water dimer.
AB  - The hydration of cucurbit[6]uril (CB[6]) in the gas phase is investigated using
      electrospray ionization traveling wave ion mobility mass spectrometry (ESI-TWIM
      MS). Highly abundant dihydrated and tetrahydrated species of diprotonated CB[6]
      are found in the ESI-TWIM-MS spectrum. The hydration patterns of the CB[6] ion
      and the dissociation patterns of the hydrated CB[6] ion indicate that two water
      molecules are bound to each other, forming a water dimer in the CB[6] complex.
      Ion mobility studies combined with the structures calculated by density
      functional theory suggest that the proton-bound water dimer is present as a
      Zundel-like structure in the CB[6] portal, forming a hydrogen bond network with
      carbonyl groups of the CB[6]. When a large guest molecule is bound to a CB[6]
      portal, water molecules cannot bind to the portal. In addition, the strong
      binding energy of the water dimer blocks the portal, hindering the insertion of
      the long alkyl chain of the guest molecule into the CB[6] cavity. With small
      alkali metal cations, such as Li(+) and Na(+), a single water molecule interacts
      with the CB[6] portal, forming hydrogen bonds with the carbonyl groups of CB[6].
      A highly stable Zundel-like structure of the proton-bound water dimer or a metal
      bound water molecule at the CB[6] portal is suggested as an initial hydration
      process for CB[6], which is only dissolved in aqueous solution with acid or
      alkali metal ions. 

PMID- 24435796
TI  - Development and investigation of a mesh-electrode linear ion trap (ME-LIT) mass
      analyzer.
AB  - A mesh-electrode linear ion trap (ME-LIT) mass analyzer was developed and its
      performance was primarily characterized. In conventional linear ion trap mass
      analyzers, the trapped ions are mass-selected and then ejected in a radial
      direction by a slot on a trap electrode. The presence of slots can strongly
      affect the electric field distribution in the ion trapping region and distort the
      mass analysis performance. To compensate for detrimental electric field effects,
      the slot is usually designed and fabricated to be as small as possible, and also
      has very high mechanical accuracy and symmetry. A ME-LIT with several mesh
      electrodes was built to compensate for the effects caused by slots. Each mesh
      electrode was fabricated from a plate electrode with a relatively large slot and
      the slot was covered with a conductive mesh. Our preliminary experimental results
      show that the ME-LIT could considerably diminish the detrimental electric field
      effects caused by slots, and increase the mass resolving power and ion detection
      efficiency. Even with 4-mm-wide slots, a mass resolution in excess of 600 was
      obtained using the ME-LIT. Mass resolution could be remarkably improved using
      mesh electrodes in ion traps with asymmetric electrodes. The stability diagram of
      the ME-LIT was mapped, and highly efficient tandem mass spectrometry was
      demonstrated. The ME-LIT was qualified as a LIT mass analyzer. The ME-LIT can
      improve the mass resolution and decrease the requirements of mechanical accuracy
      and symmetry of slots, so it shows potential for a wide range of practical uses. 

PMID- 24435797
TI  - A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor
      specificity and accelerates RNA ligation.
AB  - Archease is a 16-kDa protein that is conserved in all three domains of life. In
      diverse bacteria and archaea, the genes encoding Archease and the tRNA ligase
      RtcB are localized into an operon. Here we provide a rationale for this operon
      organization by showing that Archease and RtcB from Pyrococcus horikoshii
      function in tandem, with Archease altering the catalytic properties of the RNA
      ligase. RtcB catalyzes the GTP and Mn(II)-dependent joining of either 2',3'
      cyclic phosphate or 3'-phosphate termini to 5'-hydroxyl termini. We find that
      catalytic concentrations of Archease are sufficient to activate RtcB, and that
      Archease accelerates both the RNA 3'-P guanylylation and ligation steps. In
      addition, we show that Archease can alter the NTP specificity of RtcB such that
      ATP, dGTP or ITP is used efficiently. Moreover, RtcB variants that have
      inactivating substitutions in the guanine-binding pocket can be rescued by the
      addition of Archease. We also present a 1.4 A-resolution crystal structure of P.
      horikoshii Archease that reveals a metal-binding site consisting of conserved
      carboxylates located at the protein tip. Substitution of the Archease metal
      binding residues drastically reduced Archease-dependent activation of RtcB. Thus,
      evolution has sought to co-express archease and rtcB by creating a tRNA splicing
      operon. 

PMID- 24435799
TI  - Determinants of expression variability.
AB  - The amount of tissue-specific expression variability (EV) across individuals is
      an essential characteristic of a gene and believed to have evolved, in part,
      under functional constraints. However, the determinants and functional
      implications of EV are only beginning to be investigated. Our analyses based on
      multiple expression profiles in 41 primary human tissues show that a gene's EV is
      significantly correlated with a number of features pertaining to the genomic,
      epigenomic, regulatory, polymorphic, functional, structural and network
      characteristics of the gene. We found that (i) EV of a gene is encoded, in part,
      by its genomic context and is further influenced by the epigenome; (ii) strong
      promoters induce less variable expression; (iii) less variable gene loci evolve
      under purifying selection against copy number polymorphisms; (iv) genes that
      encode inherently disordered or highly interacting proteins exhibit lower
      variability; and (v) genes with less variable expression are enriched for house
      keeping functions, while genes with highly variable expression tend to function
      in development and extra-cellular response and are associated with human
      diseases. Thus, our analysis reveals a number of potential mediators as well as
      functional and evolutionary correlates of EV, and provides new insights into the
      inherent variability in eukaryotic gene expression. 

PMID- 24435800
TI  - The rapid size- and shape-controlled continuous hydrothermal synthesis of metal
      sulphide nanomaterials.
AB  - Continuous flow hydrothermal synthesis offers a cheap, green and highly scalable
      route for the preparation of inorganic nanomaterials which has predominantly been
      applied to metal oxide based materials. In this work we report the first
      continuous flow hydrothermal synthesis of metal sulphide nanomaterials. A wide
      range of binary metal sulphides, ZnS, CdS, PbS, CuS, Fe(1-x)S and Bi2S3, have
      been synthesised. By varying the reaction conditions two different mechanisms may
      be invoked; a growth dominated route which permits the formation of
      nanostructured sulphide materials, and a nucleation driven process which produces
      nanoparticles with temperature dependent size control. This offers a new and
      industrially viable route to a wide range of metal sulphide nanoparticles with
      facile size and shape control. 

PMID- 24435798
TI  - Dicer-related helicase 3 forms an obligate dimer for recognizing 22G-RNA.
AB  - Dicer is a specialized nuclease that produces RNA molecules of specific lengths
      for use in gene silencing pathways. Dicer relies on the correct measurement of
      RNA target duplexes to generate products of specific lengths. It is thought that
      Dicer uses its multidomain architecture to calibrate RNA product length. However,
      this measurement model is derived from structural information from a protozoan
      Dicer, and does not account for the helicase domain present in higher organisms.
      The Caenorhabditis elegans Dicer-related helicase 3 (DRH-3) is an ortholog of the
      Dicer and RIG-I family of double-strand RNA activated ATPases essential for
      secondary siRNA production. We find that DRH-3 specifies 22 bp RNAs by
      dimerization of the helicase domain, a process mediated by ATPase activity and
      the N-terminal domain. This mechanism for RNA length discrimination by a Dicer
      family protein suggests an alternative model for RNA length measurement by Dicer,
      with implications for recognition of siRNA and miRNA targets. 

PMID- 24435802
TI  - Components of genetic variance for plant survival and vigor of apple trees.
AB  - The additive and non-additive variance components were estimated from progenies
      derived from two samples of parents (representing a northern continental type
      climate) for five factors relating to plant survival and two composites of the
      factors. It was found that additive variance made up 90 and 100%, 91 and 100%, 91
      and 100%, 100 and 100%, 82 and 59%, 91 and 100%, and 90 and 100% of the total
      genetic variance for leafing-out date, leafingout percent, tip injury, stem
      damage, root damage, a shoot composite, and a shoot-root composite for the two
      samples respectively. A third sample had 100% additive variance for plant height
      while, in contrast, a sample of rootstocks, differing from each other in their
      ability to dwarf grafted scions, had approximately 50-70% additive variance for
      plant height. It was shown that breeding progress for both winter survival and
      plant height could be achieved by exploiting the additive variance, the total
      genetic variance, or (where progenies were the selection unit rather than
      individuals) by progeny selection. By exploiting the additive variance, it should
      be possible to improve plant survival and change plant height in each of several
      successive generations. It is predicted that (with the exception of selection for
      vigor in a population having a range of dwarfing abilities) potential parents
      could be efficiently screened phenotypically and so obviate the need for
      genotypic evaluation. A total of 9180 progeny trees were involved in the analyses
      considered in this paper. 

PMID- 24435801
TI  - Association of genetic variants in VEGF-A with clinical recurrence in prostate
      cancer patients treated with definitive radiotherapy.
AB  - BACKGROUND AND PURPOSE: Vascular endothelial growth factor-A (VEGF-A), a key
      regulator of tumor-induced angiogenesis, is critical for tumor growth and
      metastasization. The goal of the present study was to evaluate the prognostic
      value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical
      recurrence after definitive radiotherapy for prostate cancer. PATIENTS AND
      METHODS: The association of seven VEGF-A polymorphisms and their haplotypes with
      clinical recurrence (defined as the occurrence of local recurrence and/or distant
      metastases) in 496 prostate cancer patients treated with definitive radiotherapy
      were investigated. Genotypes were determined by 5'-nuclease (TaqMan) assays;
      haplotypes were analyzed using the Haploview program. RESULTS: Within a median
      follow-up time of 80 months, 44 patients (9 %) developed clinical recurrences.
      Haplotype analysis showed two separate blocks of high-linkage disequilibrium,
      formed by five polymorphisms (- 2578C > A, - 2489C > T, - 1498C > T, - 634G > C, 
      7C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two
      polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG,
      TG). Carriers of at least 1 copy of the ATTGC haplotype were at higher risk of
      recurrence (hazard ratio [HR] 3.83; 95 %CI 1.48-9.90, p = 0.006); for carriers of
      2 copies, the HR was 4.85 (95 %CI 1.72-13.6; p = 0.003). In multivariate
      analysis, patients harboring at least one copy of the ATTGC haplotype remained at
      increased risk of recurrence (HR 3.63, 95 %CI 1.38-9.55, p = 0.009); in patients
      carrying 2 copies, the HR was 4.72 (95 %CI 1.64-13.6, p = 0.004). CONCLUSION: Our
      findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence
      in prostate cancer patients treated with radiotherapy.

PMID- 24435803
TI  - Genetic-evolutionary studies on cultivated cannas : VI. Origin and evolution of
      ornamental taxa.
AB  - Hybridization has played a dominant and decisive role in the origin of ornamental
      cannas. This has been made possible by the ecospecific differentiation of the
      parental species, which implies lack of barriers and a good deal of recombination
      associated with reasonably high fertility.Colour differences between species are
      controlled by a number of genes and their intensifiers, inhibitors, lethals, etc.
      From recombination in interspecific hybrids of such a wide range of genes,
      segregating simultaneously and involving complex segregation, arises a wide array
      of heterozygous genotypes with new colours and colour combinations, releasing
      much genetic diversity.Hybridization has also been responsible for transgressive
      segregation, particularly in length and breadth of staminodia and luxuriance,
      affecting not only plant height but also flower size. Perhaps the most important
      single factor responsible for the evolution of ornamental cannas has been the
      repeated cycles of hybridization which have led to the breakage of size and other
      barriers; this seems to have been exploited continuously until very large flower
      size was built up and combined with other useful vegetative and floral characters
      such as colour and number of flowers per inflorescence, extended blooming period,
      cold resistance, etc. The efficient vegetative propagation made fixing of the
      useful genotypes no problem, although they may contain a high degree of
      heterozygosity and sexual sterility.Along these lines, Annee (hybrids between C.
      indica and C. glauca) and Ehemann (hybrids between C. iridiflora and C.
      warscwiczii) cannas came into being in 1848 and 1863 respectively. Although both
      were a distinct improvement over the original species, they were still relatively
      small-flowered and major improvements came roundabout 1868, when Crozy, Gladiolus
      or French Dwarf cannas (C. X generalis Bailey) were released. This group arose
      from hybrids and back crosses of the first two groups and contains diploids,
      interchange heterozygotes and autotriploids. When further intercrossing,
      inbreeding and selection yielded no significant improvement, "new blood" in the
      form of C. flaccida was introduced. The result was the release of Italian, Iris,
      Orchid or Giant flowered cannas (C. X orchiodes Bailey) in 1872. These are
      asynaptic seedless diploids and allo- or segmental allotriploids. By and large,
      Crozy cannas are the result of exploiting new genetic diversity and
      transgression, while Italian cannas owe their excellence to the luxuriance
      accompanying the introduction of C. flaccida.Next to hybridization, triploidy
      (14%) has been an important mechanism in the origin of cultivars with thicker,
      more durable and larger flower parts. The two types of triploids, autotriploids
      and segmental allotriploids, are distinguishable by their morphological and
      cytogenetical properties.It is evident that during the 44 years 1848-1892 the
      speed of evolution was rapid and its direction governed by the following
      principles of selection: increase in hardiness, reduction in height, spikes well
      above foliage, free flowering, erect flowers, increase in flower size, colour
      diversity, circular form of flowers, increase in thickness of flower parts and
      durability of flower, self shedding flowers, etc. The result has been the
      transformation of cannas from simple foliage plants to attractive ornamental
      flowers.It is noteworthy that selection for the two principal uses of canna not
      only involved different organs, but also took place in very different
      environments. While selection in ornamental canna was for floral parts under a
      temperate European climate new to Canna, that for starch involved the rhizome in
      its native habitat. It is interesting that the two different purposes of
      selection under different habitats have both ended in triploidy: in the
      ornamentals this has considerably enlarged the flowers, while in the starch
      yielding C. edulis it has enlarged the fleshy rhizome but had a very limited
      effect on the flower. 

PMID- 24435804
TI  - [Competitive selection in simple systems].
AB  - 1. The types of selection in simple population systems (haploid or asexual
      populations without specific ecological interaction), composed of two components,
      are analysed according to their mode of reproduction. The terms "expansive",
      "competitive", and "restrictive" selection are suggested for them. 2. A general
      mathematical model to describe selection processes in simple systems
      independently of the mode of reproduction is defined. It relates the parameters
      of reproductivity, natality, and mortality, selective value, population number,
      and frequency. 3. The conditions under which the selective value remains constant
      were investigated. It was shown by the Lottka-Volterra equations that this is
      only to be expected for expansive and simple competitive selection in identical
      ecological niches. 4. A simple bacterial system, composed of two E. coli strains,
      was studied experimentally. It was found, that the selective value undergoes
      rapid changes during transition from expansive to competitive selection and also
      during simple competitive selection. Adequate qualitative predictions and some
      approximate quantitative predictions of these changes could be made by analysis
      of the factors influencing selection. Effective factors were: natality, mortality
      (survival factor), carrying capacity of the environment, adaptation and niche
      differences. The niche differences appear to be due to different oxygen
      requirements and led to coexistence of the two strains. 5. The results are
      discussed with regard to the competitive exclusion principle. 

PMID- 24435805
TI  - Genotypic stability.
AB  - A description for genotypic stability was developed based on the concept of a
      genotypic stability space. Environments were considered the measurement criteria.
      The coordinate position for a genotype was determined by the deviations of
      expected yield of the genotype from its yield if stable. An expression for the
      response of a stable genotype was developed. The relative genotypic stability
      measure was defined as the distance of a genotype from the center of the
      arrangement and presented as a measure of homeostasis. The comparative genotypic
      stability measure was defined as the distance between the positions of two
      genotypes and designed to measure the similarity of stability responses. The
      development permitted the testing of hypotheses with respect to stability
      concepts. A set of regional soybean test data was evaluated. The results for
      relative stability and the regression approach were comparable. Limitations for
      the regression approach were noted. Genotypes analyzed had different homeostatic
      properties. The genotypic responses to environmental stimuli appeared to be
      unique to genotypes and difficult to predict. 

PMID- 24435806
TI  - The induction of grain size and colour mutations in rice (Oryza sativa L.) by
      radioisotopes.
AB  - Seven mutants with changes in grain size and in pigmentation of various organs
      were isolated in the M 2 and M 3 generations of the Patnai variety of winter rice
      after treatment with (32) P and (35) S. Some of these could be useful for
      breeding.The narrow grain mutant, isolated in the M 3 generation after treatment
      with (32) P, was high-yielding and had fine grains and an increased number of
      long panicles.Two short grain mutants with changed husk colour were obtained in
      the M 2 generation after treatment with (32) P. One was also early maturing.One
      purple apiculus and three purple husk mutants were isolated in the M 2 generation
      after treatment with (35) S. Some of these also had reduced plant height and
      short grains. The purple apiculus mutant bred true for stigma and apiculus
      colour, but segregated for leaf sheath colour. In purple husk mutants the
      segregation of mutant characteristics was unusual and there was manifestation of
      new characters. 

PMID- 24435807
TI  - BAFF regulates activation of self-reactive T cells through B-cell dependent
      mechanisms and mediates protection in NOD mice.
AB  - Targeting the BAFF/APRIL system has shown to be effective in preventing T-cell
      dependent autoimmune disease in the NOD mouse, a spontaneous model of type 1
      diabetes. In this study we generated BAFF-deficient NOD mice to examine how BAFF
      availability would influence T-cell responses in vivo and the development of
      spontaneous diabetes. BAFF-deficient NOD mice which lack mature B cells, were
      protected from diabetes and showed delayed rejection of an allogeneic islet
      graft. Diabetes protection correlated with a failure to expand pathogenic IGRP
      reactive CD8(+) T cells, which were maintained in the periphery at
      correspondingly low levels. Adoptive transfer of IGRP-reactive CD8(+) T cells
      with B cells into BAFF-deficient NOD mice enhanced IGRP-reactive CD8(+) T-cell
      expansion. Furthermore, when provoked with cyclophosphamide, or transferred to a
      secondary lymphopenic host, the latent pool of self-reactive T cells resident in
      BAFF-deficient NOD mice could elicit beta cell destruction. We conclude that lack
      of BAFF prevents the procurement of B-cell-dependent help necessary for the
      emergence of destructive diabetes. Indeed, treatment of NOD mice with the BAFF
      blocking compound, BR3-Fc, resulted in a delayed onset and reduced incidence of
      diabetes. 

PMID- 24435810
TI  - Serum levels of arachidonic acid metabolites change during prostate cancer
      progression.
AB  - BACKGROUND: Arachidonic acid (AA) pathway has been shown to play a role in the
      development and progression of prostate cancer (PCa). In this study we aimed to
      assess the changes in concentrations of hydroxyeicosatetraenoic acids (HETEs) in
      serum samples from patients diagnosed with PCa compared to controls. METHODS:
      HETEs were determined using ultrahigh pressure liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS). RESULTS: Elevated concentrations of 5-HETE, 8-HETE,
      11-HETE and 15-HETE were observed in 6 out of 20 patients diagnosed with PCa; no
      statistical differences with controls were observed for 12-HETE and AA in the
      discovery set. An independent validation set composed of 222 samples divided in
      five groups ranging from subjects with low PSA and no PCa, to patients with
      advanced PCa was included. In 30% of the patients in the advanced PCa group, up
      to ten times higher concentrations of the same set of HETEs were observed with a
      significant concomitant decrease of the concentration of AA. Logistic regression
      and Kaplan-Meier curves illustrate that a decreased concentration of AA is a
      predictor of PCa biochemical recurrence after radical prostatectomy (RP).
      CONCLUSIONS: From the present study we conclude that a significant association
      between AA and AA metabolites in serum and PCa progression exists, although serum
      concentrations of HETEs exhibited low sensitivity toward the diagnosis of PCa.

PMID- 24435812
TI  - Relating divergence in polychaete musculature to different burrowing behaviors: a
      study using opheliidae (Annelida).
AB  - Divergent morphologies among related species are often correlated with distinct
      behaviors and habitat uses. Considerable morphological and behavioral differences
      are found between two major clades within the polychaete family Opheliidae. For
      instance, Thoracophelia mucronata burrows by peristalsis, whereas Armandia brevis
      exhibits undulatory burrowing. We investigate the anatomical differences that
      allow for these distinct burrowing behaviors, then interpret these differences in
      an evolutionary context using broader phylogenetic (DNA-based) and morphological
      analyses of Opheliidae and taxa, such as Scalibregmatidae and Polygordiidae.
      Histological three-dimensional-reconstruction of A. brevis reveals bilateral
      longitudinal muscle bands as the prominent musculature of the body. Circular
      muscles are absent; instead oblique muscles act with unilateral contraction of
      longitudinal muscles to bend the body during undulation. The angle of helical
      fibers in the cuticle is consistent with the fibers supporting turgidity of the
      body rather than resisting radial expansion from longitudinal muscle contraction.
      Circular muscles are present in the anterior of T. mucronata, and they branch
      away from the body wall to form oblique muscles. Helical fibers in the cuticle
      are more axially oriented than those in undulatory burrowers, facilitating radial
      expansion during peristalsis. A transition in musculature accompanies the change
      in external morphology from the thorax to the abdomen, which has oblique muscles
      similar to A. brevis. Muscles in the muscular septum, which extends posteriorly
      to form the injector organ, act in synchrony with the body wall musculature
      during peristalsis: they contract to push fluid anteriorly and expand the head
      region following a direct peristaltic wave of the body wall muscles. The septum
      of A. brevis is much thinner and is presumably used for eversion of a nonmuscular
      pharynx. Mapping of morphological characters onto the molecular-based phylogeny
      shows close links between musculature and behavior, but less correlation with
      habitat.

PMID- 24435813
TI  - Direct excitation of dark plasmonic resonances under visible light at normal
      incidence.
AB  - Dark plasmon resonance modes are optical modes that have small scattering cross
      sections and are thus difficult to excite directly by light at normal incidence.
      In this paper, we propose to excite quadrupolar and higher-order modes with
      normal incident light (in the visible regime) on a continuous plasmonic metallic
      surface covering a dielectric pillar array, hence resulting in narrow-band
      perfect absorption. Different from the general electromagnetic means of inducing
      dark modes, our dark modes are due to charge densities that are electrically
      induced by the standing-wave resonance of current on the thin metal sidewall of
      pillars. This new means of exciting dark modes can significantly improve the
      excitation efficiency and also provides an easy way to excite strong higher-order
      modes. 

PMID- 24435811
TI  - Morphology, projection pattern, and neurochemical identity of Cajal's
      "centrifugal neurons": the cells of origin of the tectoventrogeniculate pathway
      in pigeon (Columba livia) and chicken (Gallus gallus).
AB  - The nucleus geniculatus lateralis pars ventralis (GLv) is a prominent retinal
      target in all amniotes. In birds, it is in receipt of a dense and topographically
      organized retinal projection. The GLv is also the target of substantial and
      topographically organized projections from the optic tectum and the visual wulst
      (hyperpallium). Tectal and retinal afferents terminate homotopically within the
      external GLv-neuropil. Efferents from the GLv follow a descending course through
      the tegmentum and can be traced into the medial pontine nucleus. At present, the
      cells of origin of the Tecto-GLv projection are only partially described. Here we
      characterized the laminar location, morphology, projection pattern, and
      neurochemical identity of these cells by means of neural tracer injections and
      intracellular fillings in slice preparations and extracellular tracer injections
      in vivo. The Tecto-GLv projection arises from a distinct subset of layer 10
      bipolar neurons, whose apical dendrites show a complex transverse arborization at
      the level of layer 7. Axons of these bipolar cells arise from the apical
      dendrites and follow a course through the optic tract to finally form very fine
      and restricted terminal endings inside the GLv-neuropil. Double-label experiments
      showed that these bipolar cells were choline acetyltransferase (ChAT)
      immunoreactive. Our results strongly suggest that Tecto-GLv neurons form a
      pathway by which integrated tectal activity rapidly feeds back to the GLv and
      exerts a focal cholinergic modulation of incoming retinal inputs.

PMID- 24435815
TI  - Resident-performed selective laser trabeculoplasty in patients with open-angle
      glaucoma.
AB  - IMPORTANCE To our knowledge, this is the first study to investigate effectiveness
      and complication rates of resident-performed selective laser trabeculoplasty
      (SLT). OBJECTIVES To evaluate the effectiveness and complications of SLT
      performed by resident ophthalmologists and to identify predictors for success.
      DESIGN, SETTING, AND PARTICIPANTS Retrospective case series of 81 patients with
      open-angle glaucoma undergoing 110 SLT procedures from November 17, 2009, through
      December 16, 2011, at the San Francisco Veterans Affairs Medical Center.
      INTERVENTION Resident-performed SLT. MAIN OUTCOMES AND MEASURES Intraocular
      pressure (IOP) reduction. Secondary outcomes included change in eyedrop
      medications, complication rates, and predictors of SLT success defined as a 20%
      reduction in IOP. RESULTS The mean IOP at baseline, defined as the average IOP of
      the 2 appointments prior to the SLT procedure, was 18.7 mm Hg. The mean decrease
      in postoperative IOP compared with baseline was 2.2 mm Hg (12%; 95% CI, 5%-19%)
      at 12 months and 3.3 mm Hg (18%; 95% CI, 13%-23%), 2.8 mm Hg (15%; 95% CI, 10%
      21%), and 3.6 mm Hg (19%; 95% CI, 11%-27%) at 3, 6, and 24 months, respectively
      (all P < .001, linear mixed-effects regression). Success rates were 36% (95% CI,
      27%-47%) at 12 months and 41% (95% CI, 31%-53%), 50% (95% CI, 40%-60%), and 39%
      (95% CI, 26%-53%) at 3, 6, and 24 months, respectively. The most common
      complication was a temporary IOP spike, with increases of at least 6 mm Hg
      occurring in 7% (95% CI, 4%-14%) of the population. The largest IOP spike was 11
      mm Hg. Increased number of laser shots performed was not associated with better
      IOP control but was associated with a reduction in number of eyedrop medications
      (P = .02). Increased baseline IOP was associated with an odds ratio for success
      of 1.24 (95% CI, 1.08-1.44) at 3 months, 1.20 (95% CI, 1.05-1.37) at 6 months,
      and 1.31 (95% CI, 1.13-1.53) at 12 months of follow-up (P = .003, P = .006, and P
      < .001, respectively, logistic regression). In a multivariate analysis, baseline
      IOP remained the greatest predictor of effectiveness. CONCLUSIONS AND RELEVANCE
      Resident-performed SLT obtains outcomes similar to the IOP reduction reported in
      the literature for attending-performed SLT with low levels of complications.
      Increasing the number of shots in a treatment session may lead to less long-term
      need for eyedrop medications. In this patient group, higher baseline IOP was the
      strongest predictor of treatment effectiveness. 

PMID- 24435814
TI  - Associations among gut permeability, inflammatory markers, and symptoms in
      patients with irritable bowel syndrome.
AB  - BACKGROUND: Alterations in gastrointestinal (GI) permeability and immune measures
      are present in some patients with irritable bowel syndrome (IBS) but the
      relationship to symptoms is poorly defined. In adults with IBS, we compared
      permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL
      10) levels, IBS life interference, and GI and psychological distress symptoms.
      METHODS: In 88 women and 18 men with IBS, GI permeability was quantitated as
      percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10
      was measured in supernatants from 72-h incubated, unstimulated PBMCs.
      Participants completed a 4-week daily diary recording IBS life interference on
      daily activities and work, IBS symptoms, and psychological distress symptoms.
      They also completed the Brief Symptom Inventory. RESULTS: The L/M ratio but not
      percent sucrose recovery was significantly correlated with IBS interference with
      activities and work and retrospectively measured anxiety and depression.
      Unstimulated PBMC production of IL-10 correlated significantly with IBS
      interference with daily work, IBS symptom score, and abdominal pain. We
      identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio
      who had substantially higher IBS interference and IBS symptom scores.
      CONCLUSIONS: Our findings suggest a distinct subgroup of IBS patients with
      alterations in gut barrier function. This subgroup is characterized by increased
      GI permeability and/or increased PBMC production of IL-10. These physiologic
      alterations reflect more severe IBS as measured by interference of IBS with daily
      activities and daily IBS symptoms.

PMID- 24435816
TI  - One-minute exercise is best for evaluation of postexercise exhaustion in
      myasthenia gravis.
AB  - INTRODUCTION: To find the best exercise duration for postexercise exhaustion by
      decrement (PEE-D) in myasthenia gravis (MG). METHODS: In 32 tests in 32 MG
      patients, repetitive nerve stimulation was performed in the abductor digiti
      quinti muscle. The 3 Hz responses for 2 s were obtained with supramaximal
      stimulation at rest, and immediately after (PE0), 30 s after (PE30s), and 1, 2,
      3, and 4 min after 10-s, 30-s, and 1-min exercises. RESULTS: Compared with the
      decrement at rest, a significantly greater decrement was found at PE2m and PE3m
      after 30-s exercise, and at PE2m, PE3m, and PE4m after 1-min exercise. In 11
      patients who showed a decremental response only with exercise, PEE-D was observed
      in 5 after 30-s exercise and in 8 after 1-min exercise. CONCLUSIONS: One-minute
      exercise is best for evaluation of PEE-D in MG.

PMID- 24435817
TI  - Rational design of a solvatochromic fluorescent uracil analogue with a dual-band
      ratiometric response based on 3-hydroxychromone.
AB  - Fluorescent nucleoside analogues with strong and informative responses to their
      local environment are in urgent need for DNA research. In this work, the design,
      synthesis and investigation of a new solvatochromic ratiometric fluorophore
      compiled from 3-hydroxychromones (3HCs) and uracil fragments are reported. 3HC
      dyes are a class of multi-parametric, environment-sensitive fluorophores
      providing a ratiometric response due to the presence of two well-resolved bands
      in their emission spectra. The synthesized conjugate demonstrates not only the
      preservation but also the improvement of these properties. The absorption and
      fluorescence spectra are shifted to longer wavelengths together with an increase
      of brightness. Moreover, the two fluorescence bands are better resolved and
      provide ratiometric responses across a broader range of solvent polarities. To
      understand the photophysical properties of this new fluorophore, a series of
      model compounds were synthesized and comparatively investigated. The obtained
      data indicate that uracil and 3HC fragments of this derivative are coupled into
      an electronic conjugated system, which on excitation attains strong charge
      transfer character. The developed fluorophore is a prospective label for nucleic
      acids. Abstract in Ukrainian: . 

PMID- 24435818
TI  - Conditional quantile residual lifetime models for right censored data.
AB  - Quantile residual lifetime function is a more comprehensive quantitative measure
      for residual lifetimes than the mean residual lifetime function. It also
      incorporates the median residual life function, which is less restrictive than
      the model based on the mean residual lifetime. In this study, we propose a
      semiparametric estimator of the conditional quantile residual lifetime under
      different covariate effects at a specified time point by the reinforcement of the
      auxiliary models. Two kind of test statistics are proposed to compare two
      quantile residual lifetimes at fixed time points. Asymptotic properties are also
      established and a revised bootstrap method is proposed to estimate the asymptotic
      variance of the estimator. Simulation studies are reported to assess the finite
      sample properties of the proposed estimator and the performance of test
      statistics in terms of type I error probabilities and powers at fixed time
      points. We also compare the proposed method with the method of Jung et al.
      (Biometrics 65:1203-1212, 2009) through simulation studies. The proposed methods
      are applied to HIV data and some interesting results are presented. 

PMID- 24435819
TI  - Postcards from the past: the Third SICOT Congress, Bologna 1936.
AB  - This manuscript describes the events and eminent personalities who animated the
      third Congress of the "Societe Internationale de Chirurgie Orthopedique et
      Traumatologie", held in Bologna (Italy) in 1936. During this meeting the Society
      acquired its definitive name and the acronym under which it is now
      internationally recognized, SICOT. Some of the most illustrious clinicians and
      scientists of those times gathered in Bologna to discuss the progress of
      orthopaedic science, thus contributing to highlight the relevance of this
      discipline in the medical field. Italian surgeon Vittorio Putti was the Congress
      Chairman and his words, together with some original pictures from his 1936 photo
      gallery, are shown to celebrate appropriately a prestigious moment in the history
      of SICOT. 

PMID- 24435820
TI  - A model for the mechanism of chloride activation of oxygen evolution in
      photosystem II.
AB  - A hypothesis is proposed to explain the function of Cl(-) in activating the
      oxygenevolving complex (OEC) of photosystem II (PS II), based on the results of
      recent (35)Cl-NMR studies. The putative mechanism involves Cl(-) binding to two
      types of sites. An intrinsic site is suggested to be composed of three histidyl
      residues (His 332 and His 337 from D1 and His 337 D2). It is proposed that Cl(-)
      binding to this site accelerates the abstraction of H(+) from water by raising
      the pKa's of the histidine imidazole groups. Cl(-) binding also stimulates the
      transfer of H(+) from this intrinsic site to a set of extrinsic sites on the 33
      kD extrinsic polypeptide. The extrinsic Cl(-) binding sites are suggested to
      involve four protein domains that are linked together by salt-bridge contacts.
      Chloride and H(+) donated from the intrinsic site attack these intramolecular
      salt-bridges in a defined sequence, thereby exposing previously inaccessible Cl(
      ) and H(+) binding sites and stimulating the oxidation of water. This hypothesis
      also proposes a possible structure for the Mn active site within the D1/D2
      complex. Specific amino-acid residues that are likely to participate as Mn
      lignads are identified on the lumenal portions of the D1 and D2 proteins that are
      different from those in the L and M subunits of photosynthetic bacteria; the
      choice of these residues is based on the metal coordination chemistry of these
      residues, their location within the polypeptide chain, the regularity of their
      spacing, and their conservation through evolution. The catalytic Mn-binding
      residues are suggested to be D-61, E-65, E-92, E-98, D-103; D-308, E-329, E-342
      and E-333 in D1, and H-62, E-70, H-88, E-97, D-101; E-313, D-334, E-338 and E-345
      in D2. Finally, this hypothesis identifies sites on both D2 and the 33 kD
      extrinsic polypeptide that might be involved in high- and low-affinity Ca(2+)
      binding. 

PMID- 24435822
TI  - Editorial notes.

PMID- 24435821
TI  - Primary photochemistry of reaction centers from the photosynthetic purple
      bacteria.
AB  - Photosynthetic organisms transform the energy of sunlight into chemical potential
      in a specialized membrane-bound pigment-protein complex called the reaction
      center. Following light activation, the reaction center produces a charge
      separated state consisting of an oxidized electron donor molecule and a reduced
      electron acceptor molecule. This primary photochemical process, which occurs via
      a series of rapid electron transfer steps, is complete within a nanosecond of
      photon absorption. Recent structural data on reaction centers of photosynthetic
      bacteria, combined with results from a large variety of photochemical
      measurements have expanded our understanding of how efficient charge separation
      occurs in the reaction center, and have changed many of the outstanding
      questions. 

PMID- 24435823
TI  - Monitoring mammary tumor progression and effect of tamoxifen treatment in MMTV
      PymT using MRI and magnetic resonance spectroscopy with hyperpolarized [1
      13C]pyruvate.
AB  - PURPOSE: To use dynamic magnetic resonance spectroscopy (MRS) of hyperpolarized
      (13)C-pyruvate to follow the progress over time in vivo of breast cancer
      metabolism in the MMTV-PymT model, and to follow the response to the anti
      estrogen drug tamoxifen. METHODS: Tumor growth was monitored by anatomical MRI by
      measuring tumor volumes. Dynamic MRS of hyperpolarized (13)C was used to measure
      an "apparent" pyruvate-to-lactate rate constant (kp) of lactate dehydrogenase
      (LDH) in vivo. Further, ex vivo pathology and in vitro LDH initial reaction
      velocity were evaluated. RESULTS: Tamoxifen significantly halted the tumor growth
      measured as tumor volume by MRI. In the untreated animals, kp correlated with
      tumor growth. The kP was somewhat but not significantly lower in the treated
      group. Studies in vitro confirmed the effects of tamoxifen on tumor growth, and
      here the LDH reaction velocity was reduced significantly in the treated group.
      CONCLUSION: These hyperpolarized (13)C MRS findings indicate that tumor metabolic
      changes affects kP. The measured kp did not relate to treatment response to the
      same extent as did tumor growth, histological evaluation, and in vitro
      determination of LDH activity.

PMID- 24435824
TI  - Insights into surgical trials: methodological challenges and solutions.
AB  - BACKGROUND: Novel surgical methods and procedures used to be introduced by
      experts and were established depending on the corresponding success that was
      noted. Surgical trials representing evidence level 1b were and still are called
      into question for different reasons. Prospective randomized controlled trials
      comparing various surgical strategies that were conducted over the past 11 years
      in the clinical trial unit in the department of general, visceral, and
      transplantation surgery of the University of Heidelberg pointed out problems as
      well as possible solutions for surgical trials' characteristics. PURPOSE: When
      planning a study within a department of surgery, several aspects have to be
      considered. The article aims at outlining pitfalls that have to be dealt with as
      well as possible solutions by outlining experiences within several conducted
      trials. CONCLUSIONS: The compilation of solutions announcing the challenges of
      surgical studies shows that valid high-quality trials are feasible.

PMID- 24435825
TI  - Relations of bromine, iron, rubidium, strontium, and zinc content to morphometric
      parameters in pediatric and nonhyperplastic young adult prostate glands.
AB  - The variation with age of the Br, Fe, Rb, Sr, and Zn mass fractions and some
      histological characteristics of intact prostate glands of 50 subjects aged 0-30
      years was investigated by an energy-dispersive X-ray fluorescence and a
      quantitative morphometric analysis. Mean values +/- standard error of the mean (M
      +/- SEpsilonMU) for the mass fractions (in milligrams per kilogram wet-mass
      basis) of these trace elements in pre-puberty were: Br-10.5 +/- 1.3, Fe-28.6 +/-
      4.1, Rb-3.05 +/- 0.27, Sr-0.42 +/- 0.08, and Zn-32.9 +/- 3.2. During puberty and
      postpuberty, when there is a significant increase in circulating androgens, the
      mean values were: Br-5.60 +/- 0.57, Fe-19.3 +/- 1.6, Rb-3.50 +/- 0.28, Sr-0.24 +/
      0.03, and Zn-113 +/- 10. Mean values (M +/- SEpsilonMU) of percent volumes (%)
      of the stroma, epithelium, and lumen in the prostate before puberty were 73.4 +/-
      2.6, 20.4 +/- 1.7, and 4.45 +/- 0.94, respectively, versus 46.5 +/- 2.5, 38.5 +/-
      1.9, and 14.9 +/- 1.2 during puberty and postpuberty. A significant positive
      correlation between the prostatic Zn and percent volume of both glandular
      epithelium (r = 0.573, p <= 0.001) and glandular lumen (r = 0.725, p <= 0.001)
      was found. For the first time, it has been demonstrated that the glandular lumen
      is a main pool of Zn accumulation, and that the stroma is a main pool of Br and
      Fe accumulation in the normal human prostate, for the age range 14 to 30 years.
      It was concluded that the Zn binds tightly within the prostatic fluid because the
      volume of glandular lumen reflects the volume of prostatic fluid.

PMID- 24435826
TI  - Evaluation of serum thyroid-stimulating hormone as indicator for fine-needle
      aspiration in patients with thyroid nodules.
AB  - BACKGROUND: Recently, it has been reported that the risk of thyroid malignancy
      increases with increasing concentrations of serum thyroid-stimulating hormone
      (TSH). The purpose of this study was to determine whether or not serum TSH can be
      a predictor for thyroid malignancy when considering the relevant ultrasound
      features and clinical risk factors. METHODS: This retrospective study included
      1200 euthyroid patients with 1269 thyroid nodules who underwent ultrasound-guided
      fine-needle aspiration (FNA) biopsy between January and June 2009. Serum TSH,
      ultrasound feature, and clinical parameters were compared according to final
      diagnosis. Subgroup analyses were performed according to nodule size. RESULTS:
      Serum TSH did not show a positive association with malignancy for all nodules and
      the micronodule subgroup in multivariate analysis, although they showed
      significant association with thyroid malignancy for the macronodule subgroup. For
      all nodules and the 2 subgroups, suspicious ultrasound features and younger age
      were significantly associated with malignancy in univariate and multivariate
      analyses. CONCLUSION: Our study suggests that TSH alone is not as useful as
      ultrasound features in deciding whether or not to perform FNA in patients with
      micronodules.

PMID- 24435827
TI  - Unveiling the role of TNF-alpha in mesenchymal stromal cell-mediated
      immunosuppression.
AB  - Mesenchymal stromal cells (MSCs) are multipotent progenitors of mesodermal origin
      that not only differentiate into osteoblasts, chondrocytes, connective stromal
      cells, and adipocytes, but also exert immunoregulatory activities, usually
      induced by soluble molecules released during the cross-talk between MSCs and
      their target immune cell populations. In this issue of the European Journal of
      Immunology, Dorronsoro et al. [Eur. J. Immunol. 2014. 44: 480-488] demonstrate
      for the first time that TNF-alpha released by activated T cells confers
      immunosuppressive properties upon MSCs by binding to TNF-R1 and activating the NF
      kB pathway. Such findings may improve our knowledge of the mechanisms underlying
      the reported efficacy of human MSCs administered locally or systemically to
      patients with autoimmune/inflammatory disorders, such as Crohn's disease and
      graft versus host disease, as discussed in this commentary. 

PMID- 24435828
TI  - [Intervention-specific complications of hernia surgery].
AB  - Hernia surgery is generally a rewarding task, patient satisfaction is high and
      the long-term results are generally good. Incisional hernias are more
      heterogeneous and there is a higher variability of morphologies to be matched
      with the available therapeutic approaches but the majority of patients are also
      satisfied with the results. This positive scenario for hernia surgery can be
      largely attributable to careful preoperative planning, effective surgical
      techniques and a high degree of standardization. The picture is somewhat clouded
      by the complications associated with hernia surgery. If complications do arise,
      the outcome largely depends on how well the surgeon responds. For inguinal and
      femoral hernias, the risk profile of the patient is crucial to the surgical
      planning and the wrong operation on the wrong patient can be disastrous. Open
      procedures have complication risks in common but the question of how best to deal
      with the nerves has yet to be answered. Endoscopic procedures are an
      indispensable part of the hernia surgery repertoire and the hernia specialist
      should be proficient in TEP and TAPP techniques. Ventral and incisional hernias
      have higher complication rates and the treatment is similar despite differences
      in etiology and pathophysiology. Although open procedures are better for
      morphological reconstruction they are accompanied by a higher complication rate.
      Laparoscopic procedures had a severe complication profile early on but the
      situation has greatly improved today due to continued refinement of the learning
      curve. A critical approach to the application of methods and meshes, a deep
      knowledge of anatomical peculiarities and the careful planning of tactics for
      dealing with intraoperative problems are the hallmarks of today's good hernia
      surgeon. 

PMID- 24435829
TI  - [Hernia surgery: minimization of complications by selection of the "correct
      mesh"].
AB  - The risk for developing postoperative complications increases with the degree of
      surgical trauma, an altered wound healing capability of the patient due to
      comorbidities and environmental conditions and the selection of an inadequate
      implant material, the latter offering options for improvement at least in some
      patients. In general a mesh with large pores made of monofilaments provides a
      reduced surface area and causes less scarring and inflammation than those with
      small pores and thereby reduces the rate of scar contraction, pain and the
      challenge to explant a mesh from a scar bed. When placing the mesh in the
      abdominal cavity an additional surface coating of polypropylene should prevent
      the formation of a fistula between mesh and bowel. The risk of recurrence mainly
      depends on the extent of overlap; however, the flexibility of some meshes may
      increase the technical difficulties of some implants. In cases of bacterial
      contamination of the wound there is an increased risk for late onset mesh
      infection and monofilament meshes offer the best option for complete healing by
      conservative means. An impaired function of the spermatic cord because of the
      material, apart from the consequences of the surgical trauma, has not been
      confirmed in experimental and clinical studies. Revision of mesh sites always is
      a surgical challenge but could be much easier with implants which are visible in
      computed tomography (CT) or magnetic resonance imaging (MRI) scans. 

PMID- 24435830
TI  - [Recurrence after hernia surgery: complication or natural course?].
AB  - Recurrence after hernia surgery remains a relevant measure of surgical quality.
      In order to correctly assess the recurrence rate the surgeon needs to distinguish
      clinical relevant recurrence, clinically irrelevant recurrence and pseudo
      recurrence. Current surgical techniques for inguinal hernia repair using mesh are
      associated with a low rate of recurrence. Thus, recurrence after inguinal hernia
      surgery is seen as a surgical complication. Conversely, the recurrence rate for
      large incisional hernias remains above 10 % and in rare cases a recurrence might
      represent the natural course. Recurrent hernia can depend on the indication,
      choice of operation and surgical technique. Therefore, postoperative hernia
      recurrence probably does not represent the natural course but rather a surgical
      complication that needs to be prevented by an optimized surgical technique. 

PMID- 24435831
TI  - [Diagnostics and therapy of chronic pain following hernia operation].
AB  - The frequency of chronic pain after hernia repair is currently much higher than
      the recurrence rate. For inguinal hernias it has been shown that mesh-based
      techniques are comparable to mesh-free techniques concerning chronic pain. Risk
      factors could be clearly identified for inguinal hernia repair and include open
      repair, meshes with small pores, mesh fixation with sutures or tacks, pre
      existing pain and severe pain during the early postoperative period. The last two
      risk factors are also important for incisional hernias. For laparoscopic
      incisional hernia repair, the width (> 10 cm) of the gap seems to correlate with
      chronic pain. The diagnostic measures are restricted to the identification of a
      segmental problem in terms of nerve entrapment which can be blocked by local
      anesthesia or definite neurectomy. In some cases of chronic pain after inguinal
      hernia repair removal of the mesh will be advisable. After incisional hernia
      repair a segmental involvement is rarely seen. Localized pain may be induced by
      stay sutures which can be removed. Mesh removal is, however, a complex procedure
      especially after open repair resulting in hernia recurrence and therefore
      represents a salvage technique. The prophylaxis of chronic pain is therefore of
      utmost importance as is the identification of patients at risk which is now
      possible. These patients for example with inguinal hernias should be treated
      laparoscopically with an adequate technique including meshes with big pores and
      without fixation or fixation with glue only. 

PMID- 24435832
TI  - [The surgical technique of laparoscopic right hemihepatectomy. Technical aspects
      and results].
AB  - INTRODUCTION: This study compared the technical aspects and results for two
      different techniques of total laparoscopic anatomical right hemihepatectomy.
      PATIENTS AND METHODS: From September 2010 to February 2013 a total of 16 patients
      underwent total laparoscopic right hemihepatectomy at the University Hospital of
      Freiburg. Of the patients 8 received an intraglissonian approach (IGA) and the
      other 8 patients an extraglissonian approach (EGA). In the patients of the IGA
      group, vascular inflow control of the right liver was accomplished by dissection
      and dividing the right hepatic artery, the right portal vein and the right bile
      duct separately before parenchymal dissection. In contrast, vascular control for
      patients in the EGA group was performed by enclosure and transsection of the
      whole right pedicle using a vascular linear stapler. RESULTS: Indications for
      right hemihepatectomy were benign tumors in 2 and malignancies in 14 cases. The
      average maximum tumor diameter was 5.5 cm (range 1.5-10.0 cm). Adequate tumor
      free surgical margins (R0) were confirmed in all patients with malignancies. The
      perioperative mortality rate was 0 %, surgical complications according to
      Clavien's classification were grade I (n = 1 trocar site superficial wound
      infection), grade II (n = 2 cholangitis) and grade IIIb (n = 1 wound dehiscence
      after conversion to open procedure). The median operating time was 366 min (range
      265-422 min) and 313 min (range 247-417 min) in the IGA and EGA groups,
      respectively. Conversion from laparoscopic to open minimal access procedure was
      necessary in three patients in the IGA group and two patients in the EGA group.
      Mean intraoperative blood loss was 644 ml (200-1000 ml) and 518 ml (200-1500 ml)
      in the IGA and EGA groups, respectively. Transfusion of two units of packed red
      blood cells was necessary for one patient in group EGA. No patient in either
      group needed a Pringle maneuver. Mean postoperative hospital stay was 11 days
      (range 7-23 days) and 13 days (range 7-31 days) in the IGA and EGA groups,
      respectively. CONCLUSIONS: Total laparoscopic anatomical right hemihepatectomy is
      a feasible procedure. The extraglissonian technique can provide shorter operating
      times by correctly facilitating vascular control of the right liver.

PMID- 24435835
TI  - [Quality of life after laparoscopic versus open surgery for rectal cancer:
      Results of a randomized trial].

PMID- 24435837
TI  - Migration of a broken scalpel into the heart after spine surgery.
AB  - Iatrogenic vascular problems during posterior lumbar interbody fusion are a rare
      entity. Migration of a broken scalpel towards the heart has, to our knowledge,
      never been reported. We present the successful surgical retrieval of a broken
      scalpel from the heart after posterior lumbar interbody fusion without the use of
      a cardiopulmonary bypass. 

PMID- 24435838
TI  - Endovascular microcatheter provocation test for the diagnosis of glossopharyngeal
      neuralgia.
AB  - OBJECTIVE: Glossopharyngeal neuralgia (GN) is a rare disease often clinically
      misdiagnosed as trigeminal neuralgia. An endovascular provocative test has been
      applied to assist in making the diagnosis of GN caused by vascular compression.
      We similarly used endovascular provocative techniques to identify the causative
      vessel and to evaluate the indication for microvascular decompression (MVD) in
      two patients. METHODS: Two patients had severe retroauricular and pharyngeal pain
      that could not be controlled by medical therapy. Magnetic resonance imaging and
      magnetic resonance angiography showed a high-riding right posterior inferior
      cerebellar artery (PICA). We decided to apply the endovascular provocation test
      to prove the assumed GN and identify potential indications for MVD. RESULT: A
      loop of the PICA appeared to compress the glossopharyngeal nerve in the first
      patient. In this patient, a microcatheter was inserted into the right PICA,
      decreasing the GN. The patient underwent MVD, resulting in complete pain relief.
      In the second patient, a microcatheter was inserted into the right PICA, and an
      attack of typical GN occurred, with pain in the posterior region of the tongue,
      tonsils, oropharynx, and larynx. The patient's severe pain was clearly different
      from this typical GN caused by the microcatheter provocation test, and MVD was
      not performed. CONCLUSION: The diagnosis of GN is sometimes complex. The
      endovascular provocative technique may allow identification of GN caused by
      vascular compression.

PMID- 24435839
TI  - Synthesis and biological evaluation of novel farnesylthiosalicylic acid
      derivatives for cancer treatment.
AB  - Novel farnesylthiosalicylic acid (FTS) derivatives were synthesized by coupling
      with different substituted diamines. Their in vitro growth inhibitory activities
      against seven human cancer cell lines were evaluated. The results revealed that
      the synthetic farnesylthiosalicylamides displayed significant antitumor
      activities compared to the positive control FTS. Especially, compound 8f
      exhibited the strongest antitumor activities with IC50 values of 6.20-7.83 uM,
      which were one- to threefold less than those of sorafenib and six- to tenfold
      less than that of FTS against each cell line in vitro. Furthermore, 8f could
      inhibit the Ras-related signaling pathway and induce SMMC-7721 cell apoptosis
      superior to FTS in a dose-dependent manner. These data indicate that 8f may hold
      greater promise as therapeutic agent for the intervention of human cancers. 

PMID- 24435841
TI  - Effects of quantum nuclear delocalisation on NMR parameters from path integral
      molecular dynamics.
AB  - The influence of nuclear delocalisation on NMR chemical shifts in molecular
      organic solids is explored using path integral molecular dynamics (PIMD) and
      density functional theory calculations of shielding tensors. Nuclear quantum
      effects are shown to explain previously observed systematic deviations in
      correlations between calculated and experimental chemical shifts, with
      particularly large PIMD-induced changes (up to 23 ppm) observed for carbon atoms
      in methyl groups. The PIMD approach also enables isotope substitution effects on
      chemical shifts and J couplings to be predicted in excellent agreement with
      experiment for both isolated molecules and molecular crystals. An approach based
      on convoluting calculated shielding or coupling surfaces with probability
      distributions of selected bond distances and valence angles obtained from PIMD
      simulations is used to calculate isotope effects. 

PMID- 24435840
TI  - Association between systemic inflammatory markers and serum prostate-specific
      antigen in men without prostatic disease - the 2001-2008 National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND: Serum prostate specific antigen (PSA) may be elevated in otherwise
      healthy men; systemic inflammation has been associated with cancer. The study of
      systemic inflammatory markers in men without clinical prostate disease, but with
      elevated PSA may characterize the subgroup of men at higher risk for subsequent
      prostate cancer. METHODS: We investigated the associations between systemic
      inflammatory markers and serum PSA in 3,164 healthy men without prostatic
      disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition
      Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C
      reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count,
      and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and
      platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as
      levels equal or greater than 4 ng/ml. RESULTS: Elevated serum PSA (194 men, 6.1%
      of the total), was significantly associated with plasma fibrinogen (ORmultiv  =
      1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv  = 1.14; 95% CI, 1.03-1.26), after
      adjustment for age, smoking, body mass index, education, race, co-morbidities,
      and use of medications. CONCLUSIONS: Markers of systemic inflammation were
      associated with elevated PSA in men without known prostatic disease. Future
      studies are needed to examine these markers' relationship with prostate cancer
      occurrence and progression.

PMID- 24435842
TI  - Mortality, attempted suicide, re-hospitalisation and prescription refill for
      clozapine and other antipsychotics in Sweden-a register-based study.
AB  - PURPOSE: The aim of this study was to analyse prescription refill, re
      hospitalisation, total mortality, mortality because of suicide and attempted
      suicide among patients who were taking various types of antipsychotics. METHODS:
      A population-based cohort study analysed all patients (n=26046) in Sweden who had
      been treated for schizophrenia from 2006 to 2009 with regard to re
      hospitalisation and prescription refill for various types of antipsychotic
      treatment. A case-control study nested within the cohort analysed all-cause
      mortality, mortality because of suicide and attempted suicide in relation to
      antipsychotic use. The study adjusted for history of hospitalisation for
      psychiatric and medical care, attempted suicide and use of antidepressants.
      RESULTS: Aripiprazole users were the only ones who showed significantly lower all
      cause risks of death, but so few events occurred among users of this relatively
      new drug that the results should be interpreted with caution. Clozapine users
      showed lower odds of death by suicide (odds ratio [OR]=0.45 [95%CI 0.20-0.98])
      and of attempted suicide (OR=0.44 [0.28-0.70]) than haloperidol users after
      adjustment for age, sex and year of discharge. Olanzapine users showed
      approximately the same favourable pattern. Patients who used clozapine were most
      likely to refill prescriptions and had lower rates of re-hospitalisation. Only
      one death and 23 cases of agranulocytosis were reported compared with 223
      suicides and 831 suicide attempts. An etiologic fraction calculation suggests
      that the use of clozapine rather than traditional drugs could have prevented 95
      suicide attempts during the period. CONCLUSION: Clozapine and olanzapine reduce
      the risk of suicide, attempted suicide and re-hospitalisation.

PMID- 24435843
TI  - [Extrakaryotic inheritance of pollen sterility in Oenothera].
AB  - In crossbreeding tests we obtained plants having the B . l genome of Oenothera
      berteriana and the extrakaryotic genes of Oenothera blandina. The plants showed
      complete male sterility. The fertility of the female sex also was extremely low.
      The condition of fertility remained unchanged after further crossbreeding tests
      with the genomes B ? and l ?. According to these results the male sterility and
      the decreased fertility of the female sex is due to incompatible interaction
      between the karyotic genes of Oenothera berteriana and the extrakaryotic genes of
      Oenothera blandina. 

PMID- 24435844
TI  - Effects of selection and drift on the dynamics of finite populations : IV. Gene
      frequency dependent selection.
AB  - A genetic model of a two allelic locus involving gene frequency dependent
      selection with overdominance or underdominance was investigated with regard to
      the probability of and the expected time to fixation of an allele in the face of
      stochastic variations arising from finite population size. Results showed the
      following: 1. If the probability of fixation is larger than for no selection, the
      case of fequency dependent selection with overdominance at equilibrium gave rise
      to the highest probability of fixation. If, however, the probability of fixation
      is less than for no selection, the case of frequency dependent selection and
      underdominance at equilibrium gives rise to the highest probability of fixation.
      2. The expected time to fixation is largest for the case of overdominance at
      equilibrium and smallest for the case of underdominance at equilibrium if 0.2< p
      < 0.8. 3. For equilibrium gene frequencies (p) above 0.8 or below 0.2 there was
      acceleration in the time to fixation. This acceleration occurred over a wide
      range of initial gene frequencies that includes the p value. 

PMID- 24435845
TI  - [Genetic investigations on the incompatibility in the Culex pipiens complex].
AB  - In crosses between populations of the mosquito Culex pipiens of different
      geographical origin three crossing types have been found (1) crosses with normal
      offspring (2) crosses with reduced offspring and (3) crosses that show almost
      total incompatibility. In the case of incompatible crosses 99.9% of the
      developing embryos are lethal and only about 0.1% of the embryos hatch and
      develop into fertile diploid females. The origin of the exceptional diploid
      females has been investigated by means of the marker genes Kuf, r, w, var, y and
      ru. These females develop from a diploid oocyte or from a diploid nucleus that
      originated by fusion of the pronucleus and the last polar body. This has been
      concluded from the frequency of homozygous and heterozygous offspring from
      heterozygous females, the frequency of equational separation of different genes
      and the distribution of cross-over gametes in the exceptional females. Based on
      the genetical data it is argued that induced meiotic parthenogenesis takes place.
      The sperm does not play any part in the production of the diploid females and the
      lethal embryos. After the activation of the egg the sperm moves to the center of
      the egg but it does not succeed to fuse with the pronucleus. As a result the
      pronucleus starts to develop into a haploid embryo in about 99.9% and only in a
      few cases is the diploidy restored by a change in the meiotic process in the egg.

PMID- 24435846
TI  - Mutagenicity of radiations and chemical mutagens in Sorghum.
AB  - A comparative study on the relative mutagenicity of radiations (X-and gamma rays)
      and chemical mutagens (EMS, MMS, dES and NEU) in inducing chlorophyll, viable and
      total mutations was made on three cultivated varieties (Co. 11, Co. 12 and Co.
      18) of Eu-Sorghum. A critical comparison of the chlorophyll, viable and total
      mutations shows that the mutation rate increased with an increase in dose up to a
      certain dose level beyond which the saturation effect was observed. EMS was found
      to be the most potent mutagen in inducing chlorophyll, viable and total
      mutations. The treatments with NEU (viable mutations) and dES (viable and total
      mutations) also proved to be effective. In a large number of cases the
      relationship between chlorophyll and total mutations was more close than that of
      viable to total mutation rates. 

PMID- 24435847
TI  - Genetic heterogeneity in natural populations of Drosophila melanogaster for
      ability to withstand dessication.
AB  - Strains set up from single inseminated females of D. melanogaster derived from
      two wild populations have been shown to differ in their ability to withstand
      dessication, as measured by mortalities after 16 hours in a dry environment, thus
      there are genes segregating in wild populations for ability to withstand
      dessication. A more detailed study on strains from one of the wild populations,
      showed that strains with high wet and dry weights lose water by dessication
      relatively less rapidly and have lower mortalities, than strains with lower wet
      and dry weights.Variability within and between five inbred strains was studied
      with results as above. Heritabilities for wet weight, dry weight, and mortality
      were 0.40, 0.41 and 0.60 respectively, showing the likelihood that the traits
      would be amenable to further genetic analysis.The relevance of the results are
      discussed in relation to stress to high temperatures, and the ecology of the
      species in general. 

PMID- 24435848
TI  - [Investigations on the interaction of selection and selfing on genetical
      equilibrium, especially in tetraploid populations. I].
AB  - In the first part of this paper the interaction of selfing, double reduction, and
      selection has been investigated with regard to the genetic variability in
      equilibrium populations. Out of the theoretically infinite number of combinations
      of factors some typical combinations have been chosen and the effect on these of
      individual factors or factors acting jointly have been described. The essential
      results are the following: 1. Under the influence of selection, random mating and
      chromosome segregation the equilibrium of populations is, according to the
      selection pattern, characterized by a central point (p=0.5), a side point (p=0.25
      or p=0.75) or an end point (p=0 or p=1). Both double reduction and selfing
      (S<1.0) affect the proportions of gametes so as to cause a diminution of the
      heterozygotes, without changing the relation of p?q. The effect of inbreeding and
      double reduction that reduces the frequencies of heterozygotes decreases with
      increasing selection pressure. Hereby, in spite of high selfing rate including
      absolute selfing, the maintenance of heterozygotes in a population is possible.
      2. Selfing and double reduction, furthermore, may cause populations to become
      fixed in an end point instead of reaching a non-trivial equilibrium, or, instead
      of fixation, reach a stable non-trivial equilibrium. Fitness relations of
      w2=w4=1.0>w1=w5>w3 lead to equilibrium positions deviating from the standard. 3.
      In the absence of selection, selfing and double reduction are antagonistic
      factors, as selfing reduces the rate of approach to the equilibrium and double
      reduction increases it. In the selection models considered here this antagonism
      is removed by the effect of selection. Both factors now work in the same
      direction, and, depending on the model of selection, either both accelerate or
      both delay the approach to the equilibrium. 4. In all selection models the
      population fitness is reduced by inbreeding as well as by double reduction with
      the exception of the conditions: w3=1.0>w1=w5>w2=w4. 

PMID- 24435849
TI  - Variation and covariation of seed weight and its components in wheat following
      irradiation, EMS, and hybridization.
AB  - Seeds from two hexaploid wheat varieties, 'Giza 150' and 'Sonora 64', and the F2
      seeds of their hybrid were given two mutagenic treatments, gamma irradiation and
      ethyl methanesulfonate (EMS), to study the type of variation and covariation in
      seed weight, width, and length induced by irradiation, EMS, and hybridization.
      Measurements of seed weight and its components were taken on 30 replicated lines
      derived from each treated and non-treated material.Both irradiation and EMS
      produced significant variability in seed weight and its components in the pure
      genetic background. The hybrid genetic background somewhat depressed the
      expression of irradiation-induced variability. The variations resulting from EMS
      and hybridization were to a great extent independent and cumulative.Neither EMS
      nor irradiation caused any significant shift in the means of seed weight, width,
      and length. The positive association between inheritance of width and length in
      irradiation-derived materials did not increase the mean seed weight compared with
      the control.The magnitude of the genetic correlations in irradiation varieties
      was double that obtained from hybrid-or EMS-derived materials. It is suggested
      that EMS mainly produced mutations of genes and/or minute chromosomal
      aberrations, whereas the genetic variation produced by gamma irradiation was
      accompanied by the loss and/or gain of large segments of the chromosomes. 

PMID- 24435850
TI  - Polymorphisms in glutathione S-transferase are risk factors for perioperative
      acute myocardial infarction after cardiac surgery: a preliminary study.
AB  - In the present study we explored glutathione S-transferase (GST) polymorphisms in
      selected patients who experienced accelerated myocardial injury following open
      heart surgery and compared these to a control group of patients without
      postoperative complications. 758 Patients were enrolled from which 132 patients
      were selected to genotype analysis according to exclusion criteria. Patients were
      divided into the following groups: Group I: control patients (n = 78) without and
      Group II.: study patients (n = 54) with evidence of perioperative myocardial
      infarction. Genotyping for GSTP1 A (Ile105Ile/Ala113Ala), B (Ile105Val/Ala113Ala)
      and C (Ile105Val/Ala113Val) alleles was performed by using real-time-PCR. The
      heterozygous AC allele was nearly three times elevated (18.5 vs. 7.7 %) in the
      patients who suffered postoperative myocardial infarction compared to controls.
      Contrary, we found allele frequency of 14.1 % for homozygous BB allele in the
      control group whereas no such allele combination was present in the study group.
      These preliminary results may suggest the protective role for the B and C alleles
      during myocardial oxidative stress whereas the A allele may represent
      predisposing risk for cellular injury in patients undergoing cardiac surgery. 

PMID- 24435851
TI  - Predictive association of copper metabolism proteins with Alzheimer's disease and
      Parkinson's disease: a preliminary perspective.
AB  - Neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease
      (PD), constitute a major worldwide health problem. Several hypothesis have been
      put forth to elucidate the basis of onset and pathogenesis of AD and PD; however,
      till date, none of these seems to clearly elucidate the complex pathoetiology of
      these disorders. Notably, copper dyshomeostasis has been shown to underlie the
      pathophysiology of several neurodegenerative diseases including AD and PD.
      Numerous studies have concluded beyond doubt that imbalance in copper homeostatic
      mechanisms in conjunction with aging causes an acceleration in the copper
      toxicity elicited oxidative stress, which is detrimental to the central nervous
      system. Amyloid precursor protein and alpha-synuclein protein involved in AD and
      PD are copper binding proteins, respectively. In this review, we have discussed
      the possible association of copper metabolism proteins with AD and PD along with
      briefly outlining the expanding proportion of "copper interactome" in human
      biology. Using network biology, we found that copper metabolism proteins,
      superoxide dismutase 1 and ceruloplasmin may represent direct and indirect link
      with AD and PD, respectively. 

PMID- 24435853
TI  - Genome Sequence of the Sulfitobacter sp. Strain 2047-Infecting Lytic Phage
      {Phi}CB2047-B.
AB  - We announce the complete genome sequence of a lytic podovirus, PhiCB2047-B, which
      infects the bacterium Sulfitobacter sp. strain 2047, a member of the Roseobacter
      clade. Genome analysis revealed PhiCB2047-B to be an N4-like phage, with its
      genome having high nucleotide similarity to other N4-like roseophage genomes. 

PMID- 24435852
TI  - Macular pigment optical density is related to cognitive function in older people.
AB  - BACKGROUND: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively
      high concentration in multiple central nervous tissues (e.g. cortex and neural
      retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple
      functions, including protection and improvement of visual performance. Also, L +
      Z in the macula are related to L + Z in the cortex. OBJECTIVE: to determine
      whether macular pigment optical density (MPOD, L + Z in the macula) is related to
      cognitive function in older adults. METHODS: participants were older adults (n =
      108, 77.6 +/- 2.7 years) sampled from the age-related maculopathy ancillary study
      of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum
      carotenoids were measured using high performance liquid chromatography. MPOD was
      assessed using heterochromatic flicker photometry. Eight cognitive tests designed
      to evaluate several cognitive domains including memory and processing speed were
      administered. Partial correlation coefficients were computed to determine whether
      cognitive measures were related to serum L + Z and MPOD. RESULTS: MPOD levels
      were significantly associated with better global cognition, verbal learning and
      fluency, recall, processing speed and perceptual speed, whereas serum L + Z was
      significantly related to only verbal fluency. CONCLUSION: MPOD is related to
      cognitive function in older people. Its role as a potential biomarker of
      cognitive function deserves further study.

PMID- 24435854
TI  - Draft Genome Sequence of the Bioelectricity-Generating and Dye-Decolorizing
      Bacterium Proteus hauseri Strain ZMd44.
AB  - Proteus hauseri ZMd44 (CGMCC 6746), as a crucial biodecolorizing, bioelectricity
      generating, and copper-resistant bacterium, is distinguished from the urinary
      pathogens Proteus penneri and Proteus mirabilis. To further investigate the
      genetic functions of this strain, the genome sequence and annotation of its open
      reading frames, which consist of 3,875,927 bp (G+C content, 38.12%), are
      presented here. 

PMID- 24435855
TI  - Full-Genome Sequences of Influenza A(H1N1)pdm09 Viruses Isolated from Finnish
      Patients from 2009 to 2013.
AB  - Here we report full-length sequencing of the first large set of influenza
      A(H1N1)pdm09 virus genomes isolated in Finland between the years 2009 and 2013
      and discuss the advantages and needs of influenza virus sequencing efforts. 

PMID- 24435856
TI  - Population of endogenous pararetrovirus genomes in carrizo citrange.
AB  - The complete genome sequences of three related endogenous pararetroviruses
      (EPRVs) were obtained by 454 sequencing of nucleic acid extracts from Carrizo
      citrange, used as a citrus rootstock. Numerous homologous sequences have been
      found in the sweet orange genome. The new EPRVs are most closely related to
      petunia vein-clearing virus. 

PMID- 24435857
TI  - Draft Genome Sequences of Type Strain Sediminibacterium salmoneum NJ-44 and
      Sediminibacterium sp. Strain C3, a Novel Strain Isolated from Activated Sludge.
AB  - The genus Sediminibacterium comprises species present in diverse natural and
      engineered environments. Here, we report for the first time the genome sequences
      of the type strain Sediminibacterium salmoneum NJ-44 (NBRC 103935) and
      Sediminibacterium sp. strain C3 (BNM541), isolated from activated sludge, a
      valuable model for the study of substrate-dependent autoaggregation. 

PMID- 24435858
TI  - Draft Genome Sequence of Rhodobacter sp. Strain CACIA 14H1, a Heterotrophic
      Bacterium Obtained from a Nonaxenic Culture of a Cyanobium Species.
AB  - Despite their prominent importance, few efforts have been paid to the genomic
      analysis of heterotrophic bacteria associated with cyanobacteria. Thus, this work
      presents the draft genome sequence (~3.9 Mbp) of a heterotrophic bacterium
      (Rhodobacter sp. strain CACIA 14H1) recovered from a nonaxenic culture of a
      Cyanobium species. 

PMID- 24435859
TI  - Whole-Genome Sequences of Streptococcus thermophilus Strains TH1435 and TH1436,
      Isolated from Raw Goat Milk.
AB  - We report the genome sequences of two Streptococcus thermophilus strains, TH1435
      and TH1436, isolated from raw goat milk devoted to the production of artisanal
      cheese in the Friuli-Venezia Giulia region in Italy. The genome sequences of
      these two quickly acidifying strains are the first available genome sequences of
      S. thermophilus strains isolated in Italy. 

PMID- 24435860
TI  - Complete Genome Sequence of Cronobacter sakazakii Strain CMCC 45402.
AB  - Cronobacter sakazakii is considered to be an important pathogen involved in life
      threatening neonatal infections. Here, we report the annotated complete genome
      sequence of C. sakazakii strain CMCC 45402, obtained from a milk sample in China.
      The major findings from the genomic analysis provide a better understanding of
      the isolates from China. 

PMID- 24435861
TI  - Complete genome sequence of border disease virus genotype 3 strain gifhorn.
AB  - The complete genome sequence of the genotype 3 border disease virus strain
      Gifhorn has been determined; this strain was originally isolated from pigs. This
      represents the consensus sequence for the virus used to produce the bacterial
      artificial chromosome (BAC) cDNA clone pBeloGif3, which yields a virus that is
      severely attenuated in cell culture. 

PMID- 24435862
TI  - Draft Genome Sequences of 11 Staphylococcus epidermidis Strains Isolated from
      Wild Mouse Species.
AB  - We report here the draft genome sequences of 11 strains of Staphylococcus
      epidermidis, a common bacterium inhabiting the skin of humans and other animals.
      These isolates, obtained from five mouse species, provide valuable information on
      the native Staphylococcus spp. of this important model organism and form a basis
      for studying host-bacterial interactions in their natural environment. 

PMID- 24435863
TI  - The Genome of the Predominant Equine Lactobacillus Species, Lactobacillus equi,
      Is Reflective of Its Lifestyle Adaptations to an Herbivorous Host.
AB  - We report the draft genome sequence of Lactobacillus equi strain DPC6820,
      isolated from equine feces. L. equi is a predominant Lactobacillus species in the
      horse hindgut microbiota. An examination of the genome identified genes and
      enzymes highlighting L. equi adaptations to the herbivorous gastrointestinal
      tract of the horse, including fructan hydrolases. This genome sequence may help
      us further understand the microbial ecology of the equine hindgut and the
      influence lactobacilli have on it. 

PMID- 24435864
TI  - Draft Genome Sequence of Kurthia huakuii LAM0618T, an Organic-Pollutant-Degrading
      Strain Isolated from Biogas Slurry.
AB  - Kurthia huakuii LAM0618(T) is a facultative anaerobic pollutant-degrading
      bacterium isolated from biogas slurry. An analysis of the draft genome sequence
      of LAM0618(T) reveals a genome size of 3,585,165 bp, with a mean G+C content of
      39.1%. The genome contains 3,560 coding sequences and 112 tRNA and 33 rRNA genes.

PMID- 24435865
TI  - Draft Genome Sequence of Saccharomyces cerevisiae IR-2, a Useful Industrial
      Strain for Highly Efficient Production of Bioethanol.
AB  - We sequenced the genome of Saccharomyces cerevisiae IR-2, which is a diploid
      industrial strain with flocculation activity and the ability to efficiently
      produce bioethanol. The approximately 11.4-Mb draft genome information provides
      useful insights into metabolic engineering for the production of bioethanol from
      biomass. 

PMID- 24435866
TI  - Draft Genome Sequence of the Model Naphthalene-Utilizing Organism Pseudomonas
      putida OUS82.
AB  - Pseudomonas putida OUS82 was isolated from petrol- and oil-contaminated soil in
      1992, and ever since, it has been used as a model organism to study the microbial
      assimilation of naphthalene and phenanthrene. Here, we report the 6.7-Mb draft
      genome sequence of P. putida OUS82 and analyze its featured pathways for
      biodegradation. 

PMID- 24435867
TI  - Draft Genome Sequence of the D-Xylose-Fermenting Yeast Spathaspora arborariae
      UFMG-HM19.1AT.
AB  - The draft genome sequence of the yeast Spathaspora arborariae UFMG-HM19.1A(T)
      (CBS 11463 = NRRL Y-48658) is presented here. The sequenced genome size is 12.7
      Mb, consisting of 41 scaffolds containing a total of 5,625 predicted open reading
      frames, including many genes encoding enzymes and transporters involved in d
      xylose fermentation. 

PMID- 24435868
TI  - Complete Genome Sequence of Hyphomicrobium nitrativorans Strain NL23, a
      Denitrifying Bacterium Isolated from Biofilm of a Methanol-Fed Denitrification
      System Treating Seawater at the Montreal Biodome.
AB  - Hyphomicrobium nitrativorans strain NL23 has been isolated from the biofilm of a
      denitrification system treating seawater. This strain has the capacity to
      denitrify using methanol as a carbon source. Here, we report the complete genome
      sequence of this strain in an effort to increase understanding of the function of
      this bacterium within the biofilm. 

PMID- 24435869
TI  - Genome Sequence of the Relapsing Fever Borreliosis Species Borrelia hispanica.
AB  - Borrelia hispanica is the etiological pathogen of tick-borne relapsing fever,
      transmitted to humans by infected Ornithodoros erraticus ticks. Here we present
      the 1,783,846-bp draft genome sequence, with an average G+C content of 28%. It
      has 2,140 open reading frames, 3 ribosomal RNAs, and 32 transfer RNAs. 

PMID- 24435870
TI  - A Circo-Like Virus Isolated from Penaeus monodon Shrimps.
AB  - A virus with a circular Rep-encoding single-stranded DNA (ssDNA) (CRESS-DNA)
      genome (PmCV-1) was isolated from Penaeus monodon shrimps in Vietnam. The gene
      structure of the 1,777-nucleotide (nt) genome was similar to that of circoviruses
      and cycloviruses, but the nucleic acid and protein sequence identities to these
      viruses were very low. 

PMID- 24435871
TI  - Genome Sequence of Lactococcus lactis subsp. lactis bv. diacetylactis LD61.
AB  - Lactococcus lactis is widely used in the dairy industry. We report the draft
      genome sequence of L. lactis subsp. lactis bv. diacetylactis LD61, an industrial
      and extensively studied strain. In contrast to the closely related and
      plasmidless strain IL1403, LD61 contains 6 plasmids, and the genome sequence
      provides additional information related to adaptation to the dairy environment. 

PMID- 24435872
TI  - Complete Genome Sequence of Sterol-Transforming Mycobacterium neoaurum Strain VKM
      Ac-1815D.
AB  - Mycobacterium neoaurum strain VKM Ac-1815D produces 4-androstene-3,17-dione as a
      major compound from phytosterols. Here, we report the complete genome sequence of
      the strain. The genome consists of a single circular 5,438,190-bp chromosome,
      with a G+C content of 66.88%, containing 5,318 putative open reading frames
      (ORFs), 46 tRNAs, and 6 rRNAs. Arrays of cholesterol metabolism genes are
      randomly clustered throughout the chromosome. 

PMID- 24435873
TI  - Genome Sequence of Martelella sp. Strain AD-3, a Moderately Halophilic Polycyclic
      Aromatic Hydrocarbon-Degrading Bacterium.
AB  - Martelella sp. strain AD-3, enriched from a petroleum-contaminated site with high
      salinity, can efficiently degrade polycyclic aromatic hydrocarbons. Here, we
      report the 4.75-Mb genome sequence of strain AD-3 with its genetic feature of
      helping to remediate environmental organic pollutants. 

PMID- 24435874
TI  - Genomic Sequencing of Two Coffee-Infecting Strains of Xylella fastidiosa Isolated
      from Brazil.
AB  - Here, we describe the draft genome sequences of two Xylella fastidiosa strains:
      Xf6c and Xf32, which have been obtained from infected coffee plants in Brazil,
      and are associated with the disease known as coffee leaf scorch (CLS). 

PMID- 24435875
TI  - Genome Sequence Analysis of the Biogenic Amine-Degrading Strain Lactobacillus
      casei 5b.
AB  - We here report a 3.02-Mbp annotated draft assembly of the Lactobacillus casei 5b
      genome. The sequence of this biogenic amine-degrading dairy isolate may help
      identify the mechanisms involved in the catabolism of biogenic amines and perhaps
      shed light on ways to reduce the presence of these toxic compounds in food. 

PMID- 24435876
TI  - Draft Genome Sequence of Blastomonas sp. Strain CACIA 14H2, a Heterotrophic
      Bacterium Associated with Cyanobacteria.
AB  - With the new methods for assembling sequence data from metagenomic samples, the
      genomic study of heterotrophic bacterium-cyanobacterium associations can now be
      improved. In this work, the draft genome sequence of Blastomonas sp. strain CACIA
      14H2, obtained from a nonaxenic culture of a Cyanobium sp., is presented. 

PMID- 24435877
TI  - Draft Genome Sequence of Frankia sp. Strain CcI6, a Salt-Tolerant Nitrogen-Fixing
      Actinobacterium Isolated from the Root Nodule of Casuarina cunninghamiana.
AB  - Members of the actinomycete genus Frankia form a nitrogen-fixing symbiosis with 8
      different families of actinorhizal plants. We report a 5.57-Mbp draft genome
      sequence for Frankia sp. strain CcI6, a salt-tolerant nitrogen-fixing
      actinobacterium isolated from root nodules of Casurina cunninghamiana grown in
      Egyptian soils. 

PMID- 24435878
TI  - Facilitating access to biodiversity information: a survey of users' needs and
      practices.
AB  - Biodiversity information is essential for understanding and managing the
      environment. However, identifying and providing the forms and types of
      biodiversity information most needed for research and decision-making is a
      significant challenge. While research needs and data gaps within particular
      topics or regions have received substantial attention, other information aspects
      such as data formats, sources, metadata, and information tools have received
      little. Focusing on the US southeast, a region of global biodiversity importance,
      this paper assesses the biodiversity information needs of environmental
      researchers, managers, and decision makers. Survey results of biodiversity
      information users' information needs, information-seeking behaviors and preferred
      information source attributes support previous conclusions that useful
      biodiversity information must be easily and quickly accessible, available in
      forms that allow integration and visualization and appropriately matched to
      users' needs. Survey results concerning additional information aspects suggest
      successful participation in both the creation and provision of biodiversity
      information include an increased focus on information search and other tools for
      data management, discovery, and description. 

PMID- 24435879
TI  - Incidence and predictors of difficult nasotracheal intubation with airway scope.
AB  - PURPOSE: The airway scope (AWS) improves views of the larynx during orotracheal
      intubation. However, the role of the AWS in routine nasotracheal intubation has
      not been studied adequately. METHODS: One hundred and three patients undergoing
      dental and maxillofacial surgery that required general anesthesia and
      nasotracheal intubation were enrolled. The study was approved by our Institution
      Review Board, and written informed consent was obtained from all patients. We
      evaluated the success rate of AWS intubation and the incidence of difficult
      nasotracheal intubation using a modified intubation difficulty scale (IDS) to
      examine preoperative characteristics and intubation profiles. Categories were
      difficult intubation (IDS >=5), mildly difficult (IDS = 1-4), and intubation
      without difficulty (IDS = 0). We also assessed the incidence of the use of Magill
      forceps or cuff inflation (the cuff of endotracheal tube is inflated with 10-15
      ml air) to guide the endotracheal tube into the glottis. RESULTS: AWS
      nasotracheal intubation was 100% successful. The cuff inflation technique was
      used in 37 patients. Neither Magill forceps nor other devices were needed for any
      patient during AWS use. The incidence of difficult nasotracheal intubation was
      10% (n = 10). Of the patients, 61% (n = 63) had mildly difficult intubation and
      29% (n = 30) had no difficulty. Patients with difficult intubation were more
      likely to be male and to have a larger tongue and a higher Cormack grade than in
      the other two groups. Complications, involving minor soft tissue injury, were
      observed in only 1 patient (1%). CONCLUSION: The AWS achieves a high success rate
      for nasotracheal intubation with cuff inflation in patients undergoing dental and
      maxillofacial surgery.

PMID- 24435882
TI  - Effect of caffeine ingestion on torque and muscle activity during resistance
      exercise in men.
AB  - INTRODUCTION: We examined the effect of caffeine ingestion on muscle torque
      production and muscle activity at different contraction speeds in trained men.
      METHODS: 10 men (mean age +/- SD=22 +/- 1.1 years) volunteered to participate. A
      double-blind, randomized cross-over design was used. Sixty minutes postingestion
      of caffeine (6 mg kg(-1) ) or placebo, participants completed 6 repetitions of
      isokientic knee extension at 3 angular velocities (30 degrees s(-1) , 150 degrees
      s(-1) , 300 degrees s(-1) ) from which peak torque was determined.
      Electromyographic activity of the vastus medialis was also collected. RESULTS:
      Repeated measures analysis of variance indicated that muscle torque production
      was significantly higher (P=0.02) with caffeine compared with placebo. A
      significant (P=0.02) substance by velocity interaction for muscle activity
      indicated significantly higher vastus medialis muscle activity in the presence of
      caffeine versus placebo, and this difference was amplified as angular velocity
      increased. CONCLUSIONS: Acute caffeine ingestion improves muscle performance and
      increases muscle activity during short-duration maximal dynamic contractions.

PMID- 24435880
TI  - A small noncoding RNA signature found in exosomes of GBM patient serum as a
      diagnostic tool.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent malignant brain
      tumor in adults, and its prognosis remains dismal despite intensive research and
      therapeutic advances. Diagnostic biomarkers would be clinically meaningful to
      allow for early detection of the tumor and for those cases in which surgery is
      contraindicated or biopsy results are inconclusive. Recent findings show that GBM
      cells release microvesicles that contain a select subset of cellular proteins and
      RNA. The aim of this hypothesis-generating study was to assess the diagnostic
      potential of miRNAs found in microvesicles isolated from the serum of GBM
      patients. METHODS: To control disease heterogeneity, we used patients with newly
      diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays
      followed by individual quantitative reverse transcriptase polymerase chain
      reaction were used to test the differences in the miRNA expression levels of
      serum microvesicles among 25 GBM patients and healthy controls paired by age and
      sex. The detected noncoding RNAs were then validated in another 50 GBM patients.
      RESULTS: We found that the expression levels of 1 small noncoding RNA (RNU6-1)
      and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM
      diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM
      diagnosis. CONCLUSIONS: Altogether our results uncovered a small noncoding RNA
      signature in microvesicles isolated from GBM patient serum that could be used as
      a fast and reliable differential diagnostic biomarker.

PMID- 24435883
TI  - Icariin-mediated inhibition of NF-kappaB activity enhances the in vitro and in
      vivo antitumour effect of 5-fluorouracil in colorectal cancer.
AB  - Colorectal cancer (CRC) is an aggressive malignancy that has a poor prognosis. 5
      Fluorouracil (5-FU) is a first line chemotherapeutic medication used in the
      treatment of gallbladder cancer; however, the efficacy is below satisfactory.
      Icariin is a natural compound that is conventionally reported to have activity
      against a variety of cancers. This study was carried out to investigate the anti
      cancer effect of icariin in CRC cells and to determine whether the compound can
      enhance the antitumour activity of 5-FU. Cell proliferation and apoptosis were
      measured using an MTT assay and flow cytometry, respectively. The activity of
      transcription factor NF-kappaB was determined by EMSA method. The expression of
      apoptosis- and proliferation-related proteins was determined by western blotting.
      The in vivo antitumour effect of combination treatment with icariin and 5-FU on
      CRC was also assessed using a murine model of CRC. Icariin sensitized the CRC
      cells to 5-FU both in vitro and in vivo. The antitumour activity of icariin and
      its potentiating effect on the antitumour activity of 5-FU implicated the
      suppression of NF-kappaB activity and consequent down-regulation of the gene
      products regulated by NF-kappaB. Our results showed that icariin, suppressed
      tumour growth and enhanced the antitumour activity of 5-FU in CRC by inhibiting
      NF-kappaB activity. Therefore, we suggest that combination of icariin with 5-FU
      might offer a therapeutic benefit to the patients with CRC; however, further
      studies are required to ascertain this proposition. 

PMID- 24435884
TI  - Anatomy of the auditory thalamocortical system in the Mongolian gerbil: nuclear
      origins and cortical field-, layer-, and frequency-specificities.
AB  - Knowledge of the anatomical organization of the auditory thalamocortical (TC)
      system is fundamental for the understanding of auditory information processing in
      the brain. In the Mongolian gerbil (Meriones unguiculatus), a valuable model
      species in auditory research, the detailed anatomy of this system has not yet
      been worked out in detail. Here, we investigated the projections from the three
      subnuclei of the medial geniculate body (MGB), namely, its ventral (MGv), dorsal
      (MGd), and medial (MGm) divisions, as well as from several of their subdivisions
      (MGv: pars lateralis [LV], pars ovoidea [OV], rostral pole [RP]; MGd: deep dorsal
      nucleus [DD]), to the auditory cortex (AC) by stereotaxic pressure injections and
      electrophysiologically guided iontophoretic injections of the anterograde tract
      tracer biocytin. Our data reveal highly specific features of the TC connections
      regarding their nuclear origin in the subdivisions of the MGB and their
      termination patterns in the auditory cortical fields and layers. In addition to
      tonotopically organized projections, primarily of the LV, OV, and DD to the AC, a
      large number of axons diverge across the tonotopic gradient. These originate
      mainly from the RP, MGd (proper), and MGm. In particular, neurons of the MGm
      project in a columnar fashion to several auditory fields, forming small- and
      medium-sized boutons, and also hitherto unknown giant terminals. The distinctive
      layer-specific distribution of axonal endings within the AC indicates that each
      of the TC connectivity systems has a specific function in auditory cortical
      processing.

PMID- 24435885
TI  - The influence of N-doped carbon materials on supported Pd: enhanced hydrogen
      storage and oxygen reduction performance.
AB  - N-doped graphene has become an important support for Pd in both hydrogen storage
      and catalytic reactions. The molecular orbitals of carbon materials (including
      graphene, fullerene, and small carbon clusters) and those of the supported Pd
      species will hybrid much stronger as N dopants are introduced, owing to the
      increased electrostatic attraction at the interface. This enhances the carbon
      substrates' catching force for the supported Pd, preventing its leaching and
      aggregation in many practical applications. The better dispersion and
      stabilization of Pd nanoparticles, which are induced by various carbon supports
      with N-doping, are pleasing to us and could increase their efficiency and
      facilitate their recycling during various reaction processes in several fields. 

PMID- 24435886
TI  - When neutrophils meet T cells: beginnings of a tumultuous relationship with
      underappreciated potential.
AB  - Neutrophils play a key role in the innate immune system's response to infection.
      They eliminate microbes through phagocytosis, the production of ROS, and the
      secretion of various proteases and antimicrobial peptides. In addition, they
      influence adaptive immune responses by modulating B-cell antibody production,
      dendritic cell activation and anti-microbial CD4(+) and CD8(+) T-cell responses.
      Here we discuss the current knowledge of the reciprocal interactions between
      neutrophils and T cells. A special emphasis is put on their interaction with
      gammadelta T cells, which respond in the early stages of infection to produce a
      pivotal source of neutrophil-recruiting IL-17. Human peripheral blood gammadelta
      T cells are activated by microbe-derived and endogenous isoprenoid pyrophosphate
      antigens, the levels of which can be enhanced by the therapeutic application of
      aminobisphosphonates. We specifically discuss intriguing new evidence showing how
      pyrophosphates and aminobisphosphonates modulate the interplay between
      neutrophils and human gammadelta T cells. 

PMID- 24435887
TI  - Strong propensity for HIV transmission among men who have sex with men in
      Vietnam: behavioural data and sexual network modelling.
AB  - OBJECTIVES: Survey data from men who have sex with men (MSM) in Asian cities
      indicate ongoing and drastic increases in HIV prevalence. It is unknown which
      behavioural factors are most important in driving these epidemics. We aimed to
      analyse detailed sexual behaviour data among MSM in Vietnam and to model HIV
      transmission using improved assumptions on sexual network structure. SETTING:
      Vietnam. PARTICIPANTS: Internet-using men who had ever had sex (any type) with a
      man, aged >=18 years and living in Vietnam. The study was cross-sectional,
      population-based and performed in 2012, using online respondent-driven sampling.
      The Internet-based survey instrument was completed by 982 participants, of which
      857 were eligible. Questions included sociodemography and retrospective sexual
      behaviour, including number of unprotected anal sex (UAS) acts per partner.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Estimated basic reproductive number over
      3 months as a function of transmission risk per UAS act; frequency distributions
      of number of UAS partners and UAS acts during last 3 months. RESULTS: 36% (CI 32%
      to 42%) reported UAS at least once during the last 3 months. 36% (CI 32% to 41%)
      had ever taken an HIV test and received the result. UAS partner numbers and
      number of UAS acts were both highly skewed and positively correlated. Using a
      weighted configuration model, taking into account partner numbers, frequency of
      UAS and their correlations, we estimated the basic reproductive number (R0) over
      3 months. The results indicated rapid transmission over a wide range of values of
      per-act transmissibility. CONCLUSIONS: Men with multiple partners had
      unexpectedly high UAS frequency per partner, paired with low HIV testing rates.
      The study highlights the importance of collecting data on frequency of UAS acts
      and indicates the need to rapidly scale-up HIV prevention services and testing
      opportunities for MSM in Vietnam.

PMID- 24435888
TI  - Analysis of the bereavement effect after the death of a spouse in the Amish: a
      population-based retrospective cohort study.
AB  - OBJECTIVE: This study investigates the association between bereavement and the
      mortality of a surviving spouse among Amish couples. We hypothesised that the
      bereavement effect would be relatively small in the Amish due to the unusually
      cohesive social structure of the Amish that might attenuate the loss of spousal
      support. DESIGN: Population-based cohort study. SETTING: The USA. PARTICIPANTS:
      10,892 Amish couples born during 1725-1900 located in Pennsylvania, Ohio and
      Indiana. All the participants are deceased. OUTCOME MEASURES: The survival time
      is 'age'; event is 'death'. Hazard ratios (HRs) of widowed individuals with
      respect to gender, age at widowhood, remarriage, the number of surviving children
      and time since bereavement. RESULTS: We observed HRs for widowhood ranging from
      1.06 to 1.26 over the study period (nearly all differences significant at
      p<0.05). Mortality risks tended to be higher in men than in women and in younger
      compared with older bereaved spouses. There were significantly increased
      mortality risks in widows and widowers who did not remarry. We observed a higher
      number of surviving children to be associated with increased mortality in men and
      women. Mortality risk following bereavement was higher in the first 6 months
      among men and women. CONCLUSIONS: We conclude that bereavement effects remain
      apparent even in this socially cohesive Amish community. Remarriage is associated
      with a significant decrease in the mortality risk among Amish individuals.
      Contrary to results from previous studies, an increase in the number of surviving
      children was associated with decreased survival rate.

PMID- 24435889
TI  - Organised colorectal cancer screening in Lampang Province, Thailand: preliminary
      results from a pilot implementation programme.
AB  - OBJECTIVE: Colorectal cancer (CRC) is the third-most and fifth-most common cancer
      in men and women, in Thailand. The increasing CRC incidence and mortality can be
      reduced by screening and treating adenomas and early cancers. A pilot CRC
      screening programme using immunochemical faecal occult blood testing (iFOBT) and
      colonoscopy for test-positives were implemented through the routine Government
      Health Services in Lampang Province, to inform the acceptability, feasibility and
      scaling-up of screening in Thailand. This report describes the implementation,
      coverage and performance indicators of this project. DESIGN: A target population
      aged 50-65 years was informed about and invited face to face to undergo CRC
      screening by community health workers (HWs). The HWs provided faecal sample
      collection kits and participants brought their samples to one of the primary
      health units or community hospitals where nurses performed iFOBT. iFOBT-positive
      persons were referred for colonoscopy at the Lampang cancer hospital, and
      endoscopic polypectomy/biopsies were performed according to the colonoscopic
      findings. Those with confirmed CRC received appropriate treatment. RESULTS: Of
      the 127 301 target population, 62.9% were screened using iFOBT between April 2011
      and November 2012. Participation was higher among women (67.8%) than men (57.8%)
      and lower in 50-54 year-old persons than in 60-65-year-olds. Of those screened,
      873 (1.1%) were found positive; positivity was higher in men (1.2%) than in women
      (1.0%). To date 627 (72.0%) iFOBT-positive persons have had colonoscopy in which
      3.7% had CRC and 30.6% had adenomas. CONCLUSIONS: The successful implementation
      of the pilot CRC screening with satisfactory process measures indicate the
      feasibility of scaling-up organised CRC screening through existing health
      services in Thailand.

PMID- 24435890
TI  - Lean thinking in hospitals: is there a cure for the absence of evidence? A
      systematic review of reviews.
AB  - OBJECTIVE: Lean interventions aim to improve quality of healthcare by reducing
      waste and facilitate flow in work processes. There is conflicting evidence on the
      outcomes of lean thinking, with quantitative and qualitative studies often
      contradicting each other. We suggest that reviewing the literature within the
      approach of a new contextual framework can deepen our understanding of lean as a
      quality-improvement method. This article theorises the concept of context by
      establishing a two-dimensional conceptual framework acknowledging lean as complex
      social interventions, deployed in different organisational dimensions and
      domains. The specific aim of the study was to identify factors facilitating
      intended outcomes from lean interventions, and to understand when and how
      different facilitators contribute. DESIGN: A two-dimensional conceptual framework
      was developed by combining Shortell's Dimensions of capability with Walshes'
      Domains of an intervention. We then conducted a systematic review of lean review
      articles concerning hospitals, published in the period 2000-2012. The identified
      lean facilitators were categorised according to the intervention domains and
      dimensions of capability provided by the framework. RESULTS: We provide a
      framework emphasising context by relating facilitators to domains and dimensions
      of capability. 23 factors enabling a successful lean intervention in hospitals
      were identified in the systematic review, where management and a supportive
      culture, training, accurate data, physicians and team involvement were most
      frequent. CONCLUSIONS: In the absence of evidence, the two-dimensional framework,
      incorporating the context, may prove useful for future research on variation in
      outcomes from lean interventions. Findings from the review suggest that
      characteristics and local application of lean, in addition to strategic and
      cultural capability, should be given further attention in healthcare quality
      improvement.

PMID- 24435891
TI  - Unsafe riding practice among electric bikers in Suzhou, China: an observational
      study.
AB  - BACKGROUND: Electric bike (E-bike)-related deaths have been increasing rapidly in
      China and such injuries may be partly attributable to unsafe riding practice.
      OBJECTIVES: To describe potentially unsafe riding behaviours among electric
      bikers (E-bikers) and to investigate factors influencing these practices in
      China. METHODS: In September 2012, a cross-sectional observation study including
      a speed measurement component was conducted in Wuzhong (an urban district) and
      Zhangjiagang (a rural district) of Suzhou, Jiangsu Province, China. Hand-held
      radar speed metres were used to read travelling speeds of E-bikes and a pro forma
      observation checklist was used to collect data on road riding practice. Mixed
      effect logistic regressions were used to calculate adjusted ORs and 95% CIs for
      the association between speeding, road rule violations and helmet use and their
      influencing factors. RESULTS: Among 800 E-bikes with a speed reading, 70.9%
      exceeded the designed speed limit of 20 km/h. Among a further 20 647 E-bikers
      observed, 38.3% did not comply with the road rules when entering intersections;
      and only 2.2% wore helmets. No regional variation was identified between urban
      and rural areas. Male E-bikers were associated with more speeding and road rule
      violations, whereas riding a pedal-equipped E-bike was associated with less road
      rule violations and less helmet use. CONCLUSIONS: Unsafe riding practices such as
      speeding, road rule violations and lack of helmet use were commonplace among E
      bikers, especially among men. The study findings indicate that measures aimed at
      improving E-bike safety are required in China.

PMID- 24435892
TI  - Analysis of variation in charges and prices paid for vaginal and caesarean
      section births: a cross-sectional study.
AB  - OBJECTIVE: To examine the between-hospital variation of charges and discounted
      prices for uncomplicated vaginal and caesarean section deliveries, and to
      determine the institutional and market-level characteristics that influence
      adjusted charges. DESIGN, SETTING AND PARTICIPANTS: Using data from the
      California Office of Statewide Health Planning and Development (OSHPD), we
      conducted a cross-sectional study of all privately insured patients admitted to
      California hospitals in 2011 for uncomplicated vaginal delivery (diagnosis
      related group (DRG) 775) or uncomplicated caesarean section (DRG 766). OUTCOME
      MEASURES: Hospital charges and discounted prices adjusted for each patient's
      clinical and demographic characteristics. RESULTS: We analysed 76 766 vaginal
      deliveries and 32 660 caesarean sections in California in 2011. After adjusting
      for patient demographic and clinical characteristics, we found that the average
      California woman could be charged as little as US$3296 or as much as US$37 227
      for a vaginal delivery, and US$8312-US$70 908 for a caesarean section depending
      on which hospital she was admitted to. The discounted prices were, on an average,
      37% of the charges. We found that hospitals in markets with middling competition
      had significantly lower adjusted charges for vaginal deliveries, while hospitals
      with higher wage indices and casemixes, as well as for-profit hospitals, had
      higher adjusted charges. Hospitals in markets with higher uninsurance rates
      charged significantly less for caesarean sections, while for-profit hospitals and
      hospitals with higher wage indices charged more. However, the institutional and
      market-level factors included in our models explained only 35-36% of the between
      hospital variation in charges. CONCLUSIONS: These results indicate that charges
      and discounted prices for two common, relatively homogeneous diagnosis groups
      uncomplicated vaginal delivery and caesarean section-vary widely between
      hospitals and are not well explained by observable patient or hospital
      characteristics.

PMID- 24435893
TI  - Early psychosocial intervention in Alzheimer's disease: cost utility evaluation
      alongside the Danish Alzheimer's Intervention Study (DAISY).
AB  - OBJECTIVE: To assess the cost utility of early psychosocial intervention for
      patients with Alzheimer's disease and their primary caregivers. DESIGN: Cost
      utility evaluation alongside a multicentre, randomised controlled trial with 3
      years of follow-up. SETTING: Primary care and memory clinics in five Danish
      districts. PARTICIPANTS: 330 community-dwelling patients and their primary
      caregivers. INTERVENTION: Psychosocial counselling and support lasting 8-12
      months after diagnosis and follow-up at 3, 6, 12 and 36 months in the
      intervention group or follow-up only in the control group. MAIN OUTCOME MEASURES:
      The primary outcome measure was the cost of additional quality-adjusted life
      years (QALYs). Costs were measured from a societal perspective, including the
      costs of healthcare, social care, informal care and production loss. QALYs were
      estimated separately for the patient and the caregiver before aggregation for the
      main analysis. RESULTS: None of the observed cost and QALY measures were
      significantly different between the intervention and control groups, although a
      tendency was noted for psychosocial care leading to cost increases with informal
      care that was not outweighed by the tendency for cost savings with formal care.
      The probability of psychosocial intervention being cost-effective did not exceed
      36% for any threshold value. The alternative scenario analysis showed that the
      probability of cost-effectiveness increased over the range of threshold values
      used if the cost perspective was restricted to formal healthcare. CONCLUSIONS: A
      multifaceted, psychosocial intervention programme was found unlikely to be cost
      effective from a societal perspective. The recommendation for practice in
      settings that are similar to the Danish setting is to provide follow-up with
      referral to available local support programmes when needed, and to restrict large
      multifaceted intervention programmes to patients and caregivers with special
      needs until further evidence for cost-effectiveness emerges. TRIAL REGISTRATION:
      The study was registered in the Clinical Trial Database as ISRCTN74848736.

PMID- 24435894
TI  - Costs for collagenase injections compared with fasciectomy in the treatment of
      Dupuytren's contracture: a retrospective cohort study.
AB  - OBJECTIVES: To compare collagenase injections and surgery (fasciectomy) for
      Dupuytren's contracture (DC) regarding actual total direct treatment costs and
      short-term outcomes. DESIGN: Retrospective cohort study. SETTING: Orthopaedic
      department of a regional hospital in Sweden. PARTICIPANTS: Patients aged 65 years
      or older with previously untreated DC of 30 degrees  or greater in the
      metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints of the
      small, ring or middle finger. The collagenase group comprised 16 consecutive
      patients treated during the first 6 months following the introduction of
      collagenase as treatment for DC at the study centre. The controls were 16
      patients randomly selected among those operated on with fasciectomy at the same
      centre during the preceding 3 years. INTERVENTIONS: Treatment with collagenase
      was given during two standard outpatient clinic visits (injection of 0.9 mg,
      distributed at multiple sites in a palpable cord, and next-day finger extension
      under local anaesthesia) followed by night-time splinting. Fasciectomy was
      carried out in the operating room (day surgery) under general or regional
      anaesthesia using standard technique, followed by therapy and splinting. PRIMARY
      AND SECONDARY OUTCOME MEASURES: Actual total direct costs (salaries of all
      medical personnel involved in care, medications, materials and other relevant
      costs), and total MCP and PIP extension deficit (degrees) measured by hand
      therapists at 6-12 weeks after the treatment. RESULTS: Collagenase injection
      required fewer hospital outpatient visits to a therapist and nurse than
      fasciectomy. Total treatment cost for collagenase injection was US$1418.04 and
      for fasciectomy US$2102.56. The post-treatment median (IQR) total extension
      deficit was 10 (0-30) for the collagenase group and 10 (0-34) for the fasciectomy
      group. CONCLUSIONS: Treatment of DC with one collagenase injection costs 33% less
      than fasciectomy with equivalent efficacy at 6 weeks regarding reduction in
      contracture.

PMID- 24435895
TI  - An investigation into drug products withdrawn from the EU market between 2002 and
      2011 for safety reasons and the evidence used to support the decision-making.
AB  - OBJECTIVES: The objective of this study was to determine the nature of evidence
      used to support the withdrawal of marketing authorisations of drug products for
      safety reasons throughout the European Union (EU) between 2002 and 2011. SETTING:
      Products withdrawn, either by a medicines agency or a marketing authorisation
      holder, during the period 2002-2011 were identified by conducting detailed
      searches of the WHO, the European Medicines Agency (EMA) and national medicines
      agency websites throughout the EU plus Norway, Iceland and Liechtenstein. The
      scientific evidence used to support the decision was identified from a search
      within PubMed, the EMA and national medicines agencies websites. Information
      about spontaneous case reports entered into EudraVigilance and unavailable on the
      EMA website was received by email from the EMA. RESULTS: 19 drugs were withdrawn
      from the market, throughout the EU, for safety reasons from 2002 to 2011. Case
      reports were cited in 95% of withdrawals (18/19) and case-control studies (4/19),
      cohort studies (4/19), randomised controlled trials (RCTs) (12/19) or meta
      analysis (5/19) were cited in 63% of withdrawals (12/19). Cardiovascular events
      or disorders were the main reason for withdrawal (9/19), followed by hepatic
      disorders (4/19) and neurological or psychiatric disorders (4/19). CONCLUSIONS:
      This study has shown that the level of evidence used to support drug withdrawal
      has improved during the past 10 years, with an increased use of case-control
      studies, cohort studies, RCTs and meta-analyses. This research has demonstrated
      that such studies have contributed to decision-making in almost two-thirds of
      cases.

PMID- 24435896
TI  - Protocol for a longitudinal qualitative study: survivors of childhood critical
      illness exploring long-term psychosocial well-being and needs--The SCETCH
      Project.
AB  - INTRODUCTION: Life-threatening critical illness affects over a quarter of a
      million children and adolescents (0-18 years old) annually in the USA and the UK.
      Death from critical illness is rare; however, survivors and their families can be
      exposed to a complex array of negative physical, psychological and social
      problems. Currently, within the literature, there is a distinct paucity of child
      and adolescent survivor self-reports, thus limiting our understanding of how
      survivors perceive this adversity and subsequently cope and grow in the long-term
      following their critical illness. This study aims to explore and understand
      psychosocial well-being and needs of critical illness survivors, 6-20 months post
      paediatric intensive care admission. METHODS AND ANALYSIS: A longitudinal,
      qualitative approach will provide a platform for a holistic and contextualised
      exploration of outcomes and mechanisms at an individual level. Up to 80
      participants, including 20 childhood critical illness survivors and 60 associated
      family members or health professionals/teachers, will be recruited. Three
      interviews, 7-9 weeks apart, will be conducted with critical illness survivors,
      allowing for the exploration of psychosocial well-being over time. A single
      interview will be conducted with the other participants enabling the exploration
      of contextual information and how psychosocial well-being may inter-relate
      between critical illness survivors and themselves. A 'tool box' of qualitative
      methods (semi-structured interviews, draw and tell, photo-elicitation, graphic
      elicitation) will be used to collect data. Narrative analysis and pattern
      matching will be used to identify emergent themes across participants. ETHICS AND
      DISSEMINATION: This study will provide an insight and understanding of
      participants' experiences and perspectives of surviving critical illness in the
      long term with specific relation to their psychosocial well-being. Multiple
      methods will be used to ensure that the findings are effectively disseminated to
      service users, clinicians, policy and academic audiences. The study has full
      ethical approval from the East Midlands Research Ethics Committee and has
      received National Health Service (NHS) governance clearance.

PMID- 24435898
TI  - Ignoring real faces: effects of valence, threat, and salience.
AB  - Facial stimuli have been shown to accrue a special status within visual
      processing, particularly when attention is prioritized to one face over another
      on the basis of affective content. This has been examined in relation to the
      ability of faces to guide or hold attention, or to resist attentional
      suppression. Previous work has shown that schematic faces can only be partially
      ignored and that the emotional valence of to-be-ignored faces has little effect.
      Given recent debates concerning the use of schematic faces, here we examined the
      ease with which photorealistic faces could be ignored. Although we found evidence
      of a partial preview benefit for these stimuli, the findings were complex, with
      stimulus salience, valence, and threat content interacting to affect both the
      strength of the benefit and target detection efficiency (Exps. 1-3). Experiment 4
      then clarified the effects of physical salience and perceived stimulus similarity
      in the previous experiments, demonstrating that a combination of these factors is
      likely to account for the search patterns observed. 

PMID- 24435897
TI  - Determinants of survival in patients with chronic myeloid leukaemia treated in
      the new era of oral therapy: findings from a UK population-based patient cohort.
AB  - OBJECTIVES: To examine contemporary survival patterns in the general population
      of patients diagnosed with chronic myeloid leukaemia (CML), and to identify
      patient groups with less than optimal outcomes. DESIGN: Prospective population
      based cohort. SETTING: The UK's Haematological Malignancy Research Network
      (catchment population 3.6 million, with >2000 new haematological malignancies
      diagnosed annually). PARTICIPANTS: All patients newly diagnosed with CML, from
      September 2004 to August 2011 and followed up to 31 March 2013. MAIN OUTCOME
      MEASURE: Incidence and survival. RESULTS: With a median diagnostic age of 59
      years, the CML age standardised (European) incidence was 0.9/100 000 (95% CIs 0.8
      to 0.9), 5-year overall survival was 78.9% (72.3 to 84.0) and 5-year relative
      survival 88.6% (81.0 to 93.3). The efficacy of treatment across all ages was
      clearly demonstrated; the relative survival curves for those under 60 and over 60
      years being closely aligned. Survival findings were similar for men and women,
      but varied with deprivation; the age and sex adjusted HR being 3.43 (1.89 to
      6.22) for deprivation categories 4-5 (less affluent) versus 1-3 (more affluent).
      None of these differences were attributable to the biological features of the
      disease. CONCLUSIONS: When therapy is freely provided, population-based survival
      for CML is similar to that reported in clinical trials, and age loses its
      prognostic significance. However, although most of the patients with CML now
      experience close to normal lifespans, those living in more deprived areas tend to
      have poorer outcomes, despite receiving the same clinical care. A significant
      improvement in overall population outcomes could be achieved if these
      socioeconomic differences, which may reflect the treatment compliance, could be
      eliminated.

PMID- 24435899
TI  - Duration perception of visual and auditory oddball stimuli: does judgment task
      modulate the temporal oddball effect?
AB  - The duration of rare stimuli (oddballs) presented within a stream of homogenous
      standards tends to be overestimated. This temporal oddball effect (OE) has been
      attributed to perceptual processes. The OE is usually assessed with a comparative
      judgment task. It has been argued, however, that this task is prone to decision
      biases. The present experiments employed comparative and equality judgments,
      since it has been suggested that equality judgments are less vulnerable to such
      biases. Experiments 1a and 1b used visual stimuli, and Experiment 2 auditory
      stimuli. The results provide no strong evidence for decision biases influencing
      the OE. In addition, computational modeling clearly suggests that the equality
      judgment is not particularly suited to distinguish between perceptual and
      decisional effects. Taken together, the pattern of the present results is most
      consistent with a perceptual origin of the OE. 

PMID- 24435902
TI  - [Investigations on the interaction of selection and selfing on genetical
      equilibrium : Especially in tetraploid populations. II].
AB  - In the second part of this paper the influence of genotypically determined
      outcrossing rates on the genetic variability of diploid populations has been
      investigated. In the proposed model it has been assumed that besides self
      pollination the plants share in a common pollen pool. Populations with and
      without selection have been taken into account. The investigations led to the
      following results: 1. Selfing of a genotype tends to have the same effect as
      selection in favour of this genotype. 2. Outcrossing rates of T 1>T 2=T 3 and T
      1=T 2<T 3 lead to trivial equilibria with a (2) respectively A (2) genotypes.
      With regard to T 1=T 3>T 2 stable non-trivial equilibria with values of p=0.5 are
      possible. For this case formulas for calculating the frequencies of genotypes
      have been specified. 3. Outcrossing rates of T 1?T 2?T 3 lead in case of
      relations of T 1>T 2>T 3 to a fixation in a(2). Relations of T 1>T 3>T 2
      respectively T 3>T 1>T 2 allow, beside a trivial stationary state, also the
      maintenance of a stable polymorphism. Calculations of the frequencies of
      genotypes are possible when the formulas specified are used. In case of the
      heterozygotes having the lowest selling rate, only trivial stationary states are
      possible, and are depending on the initial frequency. 4. Selection in favour of a
      genotype intensifies the effect of selling this genotype. In case of antagonism
      of the two factors, relatively small differences between fitness values may
      compensate for the effect of selfing. On the other hand, large differences
      between the outcrossing rates of the genotypes are necessary in order to
      compensate for the influence of selection. 

PMID- 24435901
TI  - Effect of initial-consonant intensity on the speed of lexical decisions.
AB  - In the present study, we investigated the effect of initial-consonant intensity
      on lexical decisions. Amplification was selectively applied to the initial
      consonant of monosyllabic words. In Experiment 1, young adults with normal
      hearing completed an auditory lexical decision task with words that either had
      the natural or amplified initial consonant. The results demonstrated faster
      reaction times for amplified words when listeners randomly heard words spoken by
      two unfamiliar talkers. The same pattern of results was found when comparing
      words in which the initial consonant was naturally higher in intensity than the
      low-intensity consonants, across all amplification conditions. In Experiment 2,
      listeners were familiarized with the talkers and tested on each talker in
      separate blocks, to minimize talker uncertainty. The effect of initial-consonant
      intensity was reversed, with faster reaction times being obtained for natural
      than for amplified consonants. In Experiment 3, nonlinguistic processing of the
      amplitude envelope was assessed using noise modulated by the word envelope. The
      results again demonstrated faster reaction times for natural than for amplified
      words. Across all experiments, the results suggest that the acoustic-phonetic
      structure of the word influences the speed of lexical decisions and interacts
      with the familiarity and predictability of the talker. In unfamiliar and less
      predictable listening contexts, initial-consonant amplification increases lexical
      decision speed, even if sufficient audibility is available without amplification.
      In familiar contexts with adequate audibility, an acoustic match of the stimulus
      with the stored mental representation of the word is more important, possibly
      along with general auditory properties related to loudness perception. 

PMID- 24435903
TI  - [Investigations on the interaction of selection and selfing on genetical
      equilibrium, especially in tetraploid populations. III].
AB  - In the third part of this paper the influence of genotypically determined
      outcrossing rates on the composition of tetraploid populations has been
      investigated for the stage of genetic equilibrium. In accordance with the results
      from diploid populations (2nd part) it could be shown that an equilibrium
      situation could be established simply by genotypic ally determined differences
      between selling rates, which usually are possible only under selection pressure.
      The "selective effect of selfing rates" may be compensated for by appropriate
      fitness patterns. 

PMID- 24435904
TI  - An immunochemical approach to species relationship in Triticum and some related
      species.
AB  - An immunological reaction, precipitation in gel, was produced using a rabbit
      antiserum directed to a specific protein constantly present in bread wheats (T.
      aestivum, genome AABBDD), but absent in durum wheat (T. durum Desf., genome
      AABB). This protein was isolated in the soluble-protein fraction of bread wheat
      caryopses by combined biochemical and immunological techniques.The availability
      of such a specific anti-bread wheat serum made possible the analysis of a series
      of varieties and species of wheat and of some closely related (Secale, Aegilops)
      and less closely related (Hordeum, Haynaldia) taxa to determine whether the
      protein was present or absent. Hordeum vulgare, Haynaldia villosa, Triticum
      monoccocum and Triticum turgidum gave a negative result, while positive results
      were obtained in T. aestivum, T. timopheevi, T. zhukovskyi, Secale cereale,
      Aegilops speltoides, Ae. mutica, Ae. comosa, Ae. caudata, Ae. umbellulata, Ae.
      squarrosa, and also in the artificial amphiploids (Ae. speltoides x T.
      monococcum) and (Ae. caudata x T. monococcum).It is concluded that these results
      agree closely with the classification of Triticum proposed by MacKey in 1966. The
      investigated protein not only permits the differentiation of T. aestivum from T.
      turgidum, but also T. turgidum from T. timopheevi at tetraploid level and T.
      monococcum from all the diploid species of Aegilops. 

PMID- 24435905
TI  - [Breeding rye varieties from inbred lines : I. Selfing-proportions in polycross
      progenies].
AB  - Proportions of polycross seed resulting from self-fertilization ("selfing
      proportions" in short) were ascertained in homozygous inbred lines of rye (Secale
      cereale L.). The proportions could be determined in polycross progenies by
      visually recognizable differences between mbred and hybrid plants. The influence
      of genetic and environmental factors on the variability of the selfing
      proportions was investigated.Polycross nurseries were planted in 1960 and 1961 at
      Scharnhorst, and in 1966 through 1968 at Hohenheim. Selfing-proportions were
      determined in 1961, 1962 and 1967 to 1969, respectively. Mean values varied among
      41 lines from 4.3% to 85.9%, and among years from 34.93% to 56.37%, with an
      overall mean of 46.45%. Estimates of variance components showed 57.31% of the
      phenotypic variance to be caused by genetic effects, and only 16.00% by genotype
      environment interactions. No significant variation was found between mean selfing
      proportions of lines from different varietal sources. Polycross blocks with 4
      plants per plot exhibited slightly higher selfing-proportions than blocks with 1
      plant per plot.The findings are discussed as to various possible explanations,
      and with special regard to their bearing on the evaluation of combining ability
      and on establishing synthetic varieties. 

PMID- 24435906
TI  - A comparison of mutation induction in diploid and tetraploid rice.
AB  - A comparative assessment of the frequency and spectrum of chlorophyll mutations
      in the M 2 and M 3 of three diploids and one tetraploid of rice after X
      irradiation was made. As well as a linear relationship of the frequency of
      mutations with the dose of mutagen, a saturation effect was also evident. Among
      the three diploids, the maximum frequency of mutations was observed in T. N. 1,
      followed by G. E. B. 24 and A. S. D. 8. The diploid of G. E. B. 24 showed a
      higher frequency of mutations than the tetraploid when measured on the M1 plant
      basis only. The diploids showed a higher rate of mutations in the M 2 than in the
      M3.There was no relationship between the frequency of different types of
      chlorophyll mutations and the dose of X-rays. Albina, occurred in greater
      proportion than the other types of mutations in the diploids as well as in the
      tetraploid. The diploid showed a wider spectrum in the M 2, whereas the
      tetraploid recorded the maximum types of mutations in the M 3. Striking
      differences in the spectrum and the relative frequency of each type were observed
      among the three diploids and also between the diploid G. E. B. 24 and its
      tetraploid.The frequency and spectrum of induced mutations in the diploid and
      autotetraploid provided an insight into the genetic behaviour of the diploid and
      autotetraploid of G. E. B. 24, indicating that the genetics of diploidisation of
      the existing diploid rice may give evidence on the nature of the evolutionary
      pathway. 

PMID- 24435907
TI  - Studies on the expression of somatic crossing over in Glycine max L.
AB  - Variety T219 of Glycine max L. has spontaneous yellow, dark green and double
      (yellow-dark green) spots on the leaves of plants of genotype Y 11 y 11 but no
      such spots are found on leaves of Y 11 Y 11 or y11y11 plants. It was suggested
      (Vig and Paddock, 1968) that the double spots result from somatic crossing over
      whereas the two types of single spots primarily originate from chromosomal
      disturbances.Cold shocks disproportionately increased the frequency of double
      spots, but ethyl methanesulfonate (EMS) did not do so. However, in most cases of
      each treatment, the frequency of single spots increased. It is suggested that EMS
      is not very potent in bringing about somatic recombination whereas cold shocks
      are. Plants from a sample of seeds of variety L65-1237 that had been harvested in
      1968 at Urbana, Illinois, did not express the spotting phenomenon, but plants
      from seeds harvested in 1969 at Reno did have spots. Application of mitomycin
      C(MC) to the seeds of this variety as well as of T219 increased the incidence of
      double spots manyfold indicating that MC can reveal the potential for somatic
      crossing over in a variety which might not otherwise express it. Soaking dry
      seeds of L65-1237 in aqueous solutions of MC for intervals as short as 2 hours
      was found effective in increasing the frequency of double spots. The role of MC
      in relation to DNA synthesis and somatic crossing over is discussed. Application
      of the chromosome-breaking agent, claunomycin (DM) was ineffective in causing
      double spots. 

PMID- 24435908
TI  - [Investigations of the problem of development of fluffy mycelium in cultivated
      mushrooms].
AB  - The study deals with the question of the influence of the nutrient medium upon
      appearance of a certain type of mycelium, namely the undesirable strongly fluffy
      type, which leads to decreased yields. The experiments were carried out with two
      strains of different color (each with fluffy and normal mycelium respectively).
      Six different nutrient media were tested. A lasting favorable influence of
      compost-agar was found, but only in the fluffy type of the white strain. The
      experiments also showed that it is possible to maintain fluffy and normal stringy
      types separately to some extent, by propagating only the desired type at each
      mycelium transfer. 

PMID- 24435909
TI  - Coefficients of inbreeding and homozygosity in recurrent selection: the one-locus
      case.
AB  - For selection programs which can be represented by successive self-select
      intercross cycles (such as recurrent selection or reciprocal recurrent selection)
      general recurrence formulae are developed for obtaining the coefficients of
      inbreeding and homozygosity in each cycle. The formula for the coefficient of
      inbreeding is a generalization of a result given by Sprague, et al. (1952). It is
      shown that the coefficient of parentage in the source population has a major
      effect on the coefficient of inbreeding in the following cycles as does the
      population size. The relationship of both types of coefficients and their
      importance in practical work are discussed. 

PMID- 24435910
TI  - High-resolution quantitative sodium imaging at 9.4 Tesla.
AB  - PURPOSE: Investigation of the feasibility to perform high-resolution quantitative
      sodium imaging at 9.4 Tesla (T). METHODS: A proton patch antenna was combined
      with a sodium birdcage coil to provide a proton signal without compromising the
      efficiency of the X-nucleus coil. Sodium density weighted images with a nominal
      resolution of 1 * 1 * 5 mm(3) were acquired within 30 min with an ultrashort echo
      time sequence. The methods used for signal calibration as well as for B0, B1, and
      off-resonance correction were verified on a phantom and five healthy volunteers.
      RESULTS: An actual voxel volume of roughly 40 MUL could be achieved at 9.4T,
      while maintaining an acceptable signal-to-noise ratio (8 for brain tissue and 35
      for cerebrospinal fluid). The measured mean sodium concentrations for gray and
      white matter were 36 +/- 2 and 31 +/- 1 mmol/L of wet tissue, which are
      comparable to values previously reported in the literature. CONCLUSION: The
      reduction of partial volume effects is essential for accurate measurement of the
      sodium concentration in the human brain. Ultrahigh field imaging is a viable tool
      to achieve this goal due to its increased sensitivity.

PMID- 24435911
TI  - Monte Carlo simulation of skull and knee voxel phantoms for the assessment of
      skeletal burden of low-energy photon emitters.
AB  - In case of internal contamination due to long-lived actinides by inhalation or
      injection pathway, a major portion of activity will be deposited in the skeleton
      and liver over a period of time. In this study, calibration factors (CFs) of
      Phoswich and an array of HPGe detectors are estimated using skull and knee voxel
      phantoms. These phantoms are generated from International Commission of Radiation
      Protection reference male voxel phantom. The phantoms as well as 20 cm diameter
      phoswich, having 1.2 cm thick NaI (Tl) primary and 5cm thick CsI (Tl) secondary
      detector and an array of three HPGe detectors (each of diameter of 7 cm and
      thickness of 2.5 cm) are incorporated in Monte Carlo code 'FLUKA'. Biokinetic
      models of Pu, Am, U and Th are solved using default parameters to identify
      different parts of the skeleton where activity will accumulate after an
      inhalation intake of 1 Bq. Accordingly, CFs are evaluated for the uniform source
      distribution in trabecular bone and bone marrow (TBBM), cortical bone (CB) as
      well as in both TBBM and CB regions for photon energies of 18, 60, 63, 74, 93,
      185 and 238 keV describing sources of (239)Pu, (241)Am, (238)U, (235)U and
      (232)Th. The CFs are also evaluated for non-uniform distribution of activity in
      TBBM and CB regions. The variation in the CFs for source distributed in different
      regions of the bones is studied. The assessment of skeletal activity of actinides
      from skull and knee activity measurements is discussed along with the errors. 

PMID- 24435912
TI  - Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture
      therapy.
AB  - Monte Carlo simulations were performed to evaluate dose for possible treatment of
      cancers by boron neutron capture therapy (BNCT). The computational model of male
      Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the
      lung. Calculations have been performed by means of the MCNP5/X code. In this
      simulation, two opposite neutron beams were considered, in order to obtain
      uniform neutron flux distribution inside the lung. The obtained results indicate
      that the lung cancer could be treated by BNCT under the assumptions of
      calculations. 

PMID- 24435913
TI  - Measurements of gamma dose and thermal neutron fluence in phantoms exposed to a
      BNCT epithermal beam with TLD-700.
AB  - Gamma dose and thermal neutron fluence in a phantom exposed to an epithermal
      neutron beam for boron neutron capture therapy (BNCT) can be measured by means of
      a single thermoluminescence dosemeter (TLD-700). The method exploits the shape of
      the glow curve (GC) and requires the gamma-calibration GC (to obtain gamma dose)
      and the thermal-neutron-calibration GC (to obtain neutron fluence). The method is
      applicable for BNCT dosimetry in case of epithermal neutron beams from a reactor
      because, in most irradiation configurations, thermal neutrons give a not
      negligible contribution to the TLD-700 GC. The thermal neutron calibration is not
      simple, because of the impossibility of having thermal neutron fields without
      gamma contamination, but a calibration method is here proposed, strictly bound to
      the method itself of dose separation. 

PMID- 24435914
TI  - A Janus-headed Lewis superacid: simple access to, and first application of Me3Si
      F-Al(OR(F))3.
AB  - Upon reaction of gaseous Me3SiF with the in situ prepared Lewis acid Al(OR(F))3,
      the stable ion-like silylium compound Me3 Si-F-Al(OR(F))3 1 forms. The Janus
      headed 1 is a readily available smart Lewis acid that differentiates between hard
      and soft nucleophiles, but also polymerizes isobutene effectively. Thus, in
      reactions of 1 with soft nucleophiles (Nu), such as phosphanes, the silylium side
      interacts in an orbital-controlled manner, with formation of [Me3Si-Nu](+) and
      the weakly coordinating [F-Al(OR(F))3](-) or [((F)RO)3Al-F-Al(OR(F))3](-) anions.
      If exchanged for hard nucleophiles, such as primary alcohols, the aluminum side
      reacts in a charge-controlled manner, with release of FSiMe3 gas and formation of
      the adduct R(H)O-Al(OR(F))3. Compound 1 very effectively initiates polymerization
      of 8 to 21 mL of liquid C4 H8 in 50 mL of CH2 Cl2 already at temperatures between
      -57 and -30  degrees C with initiator loads as low as 10 mg in a few seconds with
      100% yield but broad polydispersities.

PMID- 24435916
TI  - Temperature-sensitive expression of auxin-autotrophy by crown-gall teratoma cells
      of tobacco.
AB  - Crown-gall teratoma tissues of tobacco (Nicotiana tabacum L.) grow in culture at
      25 degrees  in the absence of added auxin or cell-division factors. The capacity
      of these tissues to grow without added auxin is temperature sensitive. At 35
      degrees  auxin provided as alpha-naphthalene acetic acid or 2,4
      dichlorophenoxyacetic acid is required for continued exponential growth. Moreover
      at 35 degrees  the auxin dose response of teratoma tissues shifts from the
      pattern characteristic of autonomous tumor tissues at 25 degrees  to the pattern
      characteristic of auxin-requiring normal tissues. Incubation of the tissues at 35
      degrees  also appears to induce lasting changes in teratoma phenotype. Using
      relative growth of tissues with and without added auxin as a criterion,
      pretreatment with auxin induces a stable increase in auxin-autotrophy, while
      pretreatment without auxin induces a stable decrease in auxin-autotrophy. These
      results are consistent with a positive feedback mechanism for stable changes in
      auxin-autotrophy. 

PMID- 24435915
TI  - Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic
      cancer patient-derived orthotopic xenograft (PDOX).
AB  - The aim of this study is to determine the efficacy of tumor-targeting Salmonella
      typhimurium A1-R (A1-R) on pancreatic cancer patient-derived orthotopic
      xenografts (PDOX). The PDOX model was originally established from a pancreatic
      cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently
      transplanted by surgical orthotopic implantation (SOI) in transgenic nude red
      fluorescent protein (RFP) mice in order that the PDOX stably acquired red
      fluorescent protein (RFP)-expressing stroma for the purpose of imaging the tumor
      after passage to non-transgenic nude mice in order to visualize tumor growth and
      drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or
      standard chemotherapy, including gemcitabine (GEM), which is first-line therapy
      for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly
      reduced tumor weight, as well as tumor fluorescence area, compared to untreated
      control (P = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU.
      Histopathological response to treatment was defined according to Evans's criteria
      and A1-R had increased efficacy compared to standard chemotherapy. The present
      report is the first to show that A1-R is effective against a very low-passage
      patient tumor, in this case, pancreatic cancer. The data of the present report
      suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal
      and treatment-resistant disease and may be most effectively used in combination
      with other agents.

PMID- 24435917
TI  - Xylem to phloem transfer of solutes in fruiting shoots of legumes, studied by a
      phloem bleeding technique.
AB  - Comparisons were made of the levels of various solutes in xylem (tracheal) sap
      and fruit tip phloem sap of Lupinus albus (L.) and Spartium junceum (L.). Sucrose
      was present at high concentration (up to 220 mg ml(-1)) in phloem but was absent
      from xylem whereas nitrate was detected in xylem (up to 0.14 mg ml(-1)) but not
      in phloem. Total amino acids reached 0.5-2.5 mg ml(-1) (in xylem) versus 16-40 mg
      ml(-1) in phloem. Phloem: xylem concentration ratios for mineral nutrients (K,
      Na, Mg, Ca, Fe, Zn, Mn, Cu) spanned the range 0.7 to 20, the ratios generally
      reflecting an element's phloem mobility and its availability to the xylem from
      the roots.The accessibility of nitrate to xylem and phloem was studied in
      Lupinus. Increasing the nitrate supply to roots from 100 to 1000 mg NO3-Nl(-1)
      increased nitrate spill over into xylem, but nitrate always failed to appear in
      phloem. However, phloem loading of small amounts of nitrate was induced by
      feeding 750 or 1000 mg NO3-Nl(-1) directly to cut shoots via the transpiration
      stream. Transfer of reduced nitrogen to phloem was demonstrated by feeding
      (15)NO3 to shoots and recovering (15)N-enriched amides and amino acids in phloem
      sap. Increased nitrate supply to roots led to increased amino acid levels in
      xylem and phloem but did not alter markedly the balance between individual amino
      acids.The fate of xylem-fed (14)C-labelled asparagine, glutamine and aspartic
      acid and of photosynthetically fed (14)CO2 was studied in Spartium, with
      reference to phloem transport to seeds. Substantial fractions of the (14)C of all
      sources appeared in non-amino compounds. [(14)C]asparagine passed largely in
      unchanged form to the phloem whereas the (14)C from aspartic acid or glutamine
      appeared in phloem attached to other amino acids (e.g. asparagine and glutamic
      acid). Serine, asparagine and glutamine were the main amino compounds labelled in
      phloem sap after feeding (14)CO2. The wide distribution of (14)C amongst free and
      bound amino acids of seeds suggested that extensive metabolism of phloem-borne
      solutes occurred in the fruits. 

PMID- 24435918
TI  - Ammonium repression of nitrate reductase formation in Lemna minor L.
AB  - The presence of ammonium is shown to inhibit the nitrate-promoted formation of
      nitrate reductase in Lemna minor L. The ammonium inhibition does not result from
      an inhibition of nitrate accumulation. The kinetics of the ammonium inhibition
      suggest it is not a direct effect of ammonium. The inhibition could result from
      the build up of a product of ammonium assimilation or an ammonium induced
      regulatory protein. It is suggested that both the nitrate stimulation and the
      'ammonium' inhibition of nitrate reductase formation can be accounted for by a
      transcriptional control system. 

PMID- 24435919
TI  - Ammonium inactivation of nitrate reductase in Lemna minor L.
AB  - The addition of ammonium to nitrate induced plants of Lemna minor L. brings about
      a rapid loss in extractable nitrate reductase activity. This inactivation is
      reversible both in vivo and in vitro. Inhibitors of RNA and protein synthesis do
      not protect nitrate reductase against ammonium inactivation. It is suggested that
      factors, in addition to ammonium ions, are components of the inactivating system.
      Inactivation may involve some form of protein-protein interaction. The
      physiological significance of rapid ammonium inactivation of nitrate reductase is
      discussed. 

PMID- 24435920
TI  - Location of enzymes metabolising sucrose and starch in the grasses Pennisetum
      purpureum and Muhlenbergia montana.
AB  - Leaf tissue of the panicoid grass Pennisetum purpureum (Schum) and of the
      chloridoid grass Muhlenbergia montana (Hitchcock) were fractionated to produce
      preparations enriched in the contents of mesophyll and bundle sheath cells.
      Sucrose phosphate synthetase and sucrose synthetase were found predominantly in
      the mesophyll tissues of both species, as was uridine-diphosphate-glucose
      pyrophosphorylase in Pennisetum. In Muhlenbergia this enzyme was more plentiful
      in the bundle sheath cell fraction.Starch synthetase and adenosine-diphosphate
      glucose pyrophosphorylase were plentiful in bundle sheath extracts of both
      species but phosphorylase was associated with extracts of mesophyll cells. In no
      case was there a clear-cut compartmentation of enzymes between leaf fractions. 

PMID- 24435921
TI  - [Localisation of acropetal transport of 2-[(14)C]abscisic acid in roots of
      Phaseolus coccineus L. and evidence for a radial ABA-translocation between stele
      and cortex].
AB  - Acropetal polarity of ABA-transport in roots of runner beans is found to be
      located strictly in the stele. ABA movement in the cortex is very slow and
      unpolar. Experiments on partly decorticated and desteled roots gave evidence for
      a radial ABA-transport between the stele and cortex. Thus an ABA distribution
      quotient stele/cortex of 12/1 (expressed on tissue volume basis) is established
      after 9 h ABA incubation. The radial ABA-translocation is strongly inhibited at
      low temperature. 

PMID- 24435922
TI  - [Effect of light on transport of 2-[(14)C]abscisic acid through root segments of
      runner beans].
AB  - Light promotes the acropetal movement of 2-[(14)C]ABA through root segments of
      Phaseolus coccineus L. The promotion occurs only when the segments are irradited
      during the transport period. Red light and blue light are as effective as white
      light. There is no significant promotion when the segments are irradiated with
      green light or when they are kept in darkness during the transport period after
      preceding light treatment. Light has no effect on basipetal ABA-transport. 

PMID- 24435923
TI  - The composition and development of cell walls of Fucus embryos.
AB  - Changes in the structure and composition of cell walls of Fucus gardneri Silva
      were related to embryo development. Results of histochemical treatments of walls
      from embryos of different ages were compared with those of differential
      extractions and electronmicroscopic examinations of isolated walls. At 24 h after
      fertilization alginic acid, fucoidin and cellulose were structural constituents
      of the embryo wall. The distribution of alginic acid and cellulose was uniform
      over the cell walls of embryos of any age, but fucoidin was concentrated at the
      rhizoid end of cell walls isolated from germinated embryos. Evidence is presented
      for the presence of sulfated xylogalactofucoglucuronan and beta,1-3 glucan in the
      embryo cell-wall. Electron micrographs of untreated and differentially extracted
      cell walls showed that alginic acid comprised the fibrillar material and fucoidin
      comprised the amorphous material of the wall. Fucus eggs do not have cell walls
      and the zygotes began wall synthesis within 40 min after fertilization. During
      the first 2 h there was a rapid deposition of alginic acid. After 4 h the wall
      thickness increased linearly through 24 h. Embryos treated with cycloheximide
      ceased wall growth after 6 h. Wall isolated from 24-h-old cycloheximide-treated
      embryos resembled wall isolated from control embryos 2-4 h old. 

PMID- 24435924
TI  - Inhibition of ion accumulation in maize roots by abscisic acid.
AB  - An inhibition of root growth, a decrease in the amount of potassium (as (86)Rb)
      and phosphate ((32)P) accumulation by the root, and a partial depolarization of
      transmembrane electropotential were observed to develop with a similar time
      course and to a similar extent when intact maize (Zea mays L.) roots were treated
      with 10(-5) M abscisic acid (ABA). Potassium uptake was inhibited by ABA when
      excised, low-salt roots were bathed in KCl, KH2PO4, or K2SO4. ABA did not affect
      the ATP content of the tissues, the activity of isolated mitochondria, nor the
      activity of microsomal K(+)-stimulated ATPases. 

PMID- 24435925
TI  - Carotenoids and epoxide cycles in mature-green tomatoes.
AB  - The concentration of total xanthophylls in maturing tomato fruit (Lycopersicon
      esculentum Mill. cv. Moneymaker) passed through a minimum during the period
      comprising the mature-green and breaker stages. This period marked a rapid
      decrease in chlorophyll and preceded the accumulation of lycopene and its
      colorless precursors, phytoene and phytofluene. An epoxide cycle was found to
      operate in the mature-green fruit, as evidenced by the increase in concentration
      of zeaxanthin at the expense of violaxanthin upon illumination of the fruit with
      visible light, whereas in the dark, the reverse process occurred. A second
      epoxide cycle of lesser amplitude was observed between lutein and lutein
      monoepoxide. 

PMID- 24435926
TI  - Post meiotic nucleo-cytoplasmic interaction in Pinus banksiana: The secretion of
      RNA by the nucleus.
AB  - Using digestion with specific enzymes, the chemical nature has been resolved of
      components of the nuclear invaginations formed in post-meiotic microspores of
      Pinus banksiana (Lamb.). The content of the invaginations is formed almost
      entirely of RNA, while the main bulk of the granular material investing the
      narrow part of the invaginations is also RNA. The membranes composing the narrow
      portion of the invaginations are themselves sensitive to RNase.These data are
      considered as supporting further the hypothesis that the invaginations are
      involved in the passage and organisation of information-carrying macromolecules. 

PMID- 24435927
TI  - Cold-induced sweetening of tissue cultures of Solanum tuberosum L.
AB  - Callus cultures derived from tubers of Solanum tuberosum L. cv. "Record" were
      transferred from a complete medium to a maintenance medium that lacked sugar and
      were then incubated at 2 degrees  or 25 degrees . Incubation at 2 degrees  for 5
      days led to an accumulation of sucrose. This accumulation did not occur at the
      expense of stored reducing sugars and was not found at 25 degrees . Such cultures
      could be used for the study of cold-induced sweetening in potatoes. 

PMID- 24435928
TI  - ERG-SOX4 interaction promotes epithelial-mesenchymal transition in prostate
      cancer cells.
AB  - BACKGROUND: Approximately 50% of prostate cancer (PCa) patients in Western
      countries harbor ERG rearrangement with concurrent ERG overexpression.
      Overexpression of SOX4 has been shown to play important roles in multiple cancers
      including PCa. However, the link between these two critical genetic aberrations
      was unclear. METHODS: Fluorescence in situ hybridization and immunohistochemistry
      were utilized to detect ERG rearrangement and SOX4 expression. Cellular function
      was evaluated by transwell, wound healing assays, and cell adhesion assay,
      respectively. Interaction between ERG and SOX4 was arrayed by co
      immunoprecipitation, Real-time PCR, Western blot, and siRNA. Direct binding of
      ERG to the promoter of SOX4, as well as epigenetic modifications of their
      promoters after TGF-beta1 treatment was monitored by chromatin
      immunoprecipitation. RESULTS: ERG regulated SOX4 expression via binding to its
      promoter. Silencing both of them showed duplicate effects on restoring the
      epithelial characteristics, increasing cellular adhesion and decreasing capacity
      of cellular migration and invasion. ERG and SOX4 have cooperative roles in TGF
      beta1-induced epithelial to mesenchymal transition (EMT) process. In addition,
      TGF-beta1 stimulation increased levels of chromatin marks associated with active
      genes (H3K4me3, H416ac), and decreased levels of repressive marks (H3K27me3) at
      their promoters. 5-aza and TSA treatment changed expressions of ERG and SOX4.
      Clinically, overexpression of SOX4 is associated with ERG rearrangement status in
      PCa and ERG+/SOX4+ defined a subset of PCa patients with poor prognosis.
      CONCLUSION: Our findings define a key role for ERG/SOX4 in the development of a
      subset of PCa and highlight the clinical importance of identifying molecularly
      defined tumor subgroups.

PMID- 24435929
TI  - Potential effects of molecular testing of indeterminate thyroid nodule fine
      needle aspiration biopsy on thyroidectomy volume.
AB  - BACKGROUND: Increasing utilization of genetic expression profiling (GEP) for
      thyroid nodules with indeterminate fine needle aspiration (FNA) results will
      potentially decrease the number of patients requiring diagnostic thyroidectomy.
      This study sought to determine the potential effects of GEP for indeterminate
      thyroid FNA results on thyroidectomy volume. METHODS: A retrospective review of
      thyroidectomy procedures performed over 1 year at the University of Michigan in
      the endocrine surgery division evaluated the indications for thyroidectomy, FNA
      Bethesda classification, and final surgical pathology to determine how
      application of GEP on indeterminate FNA results would affect decision for surgery
      and subsequent thyroidectomy volume. RESULTS: During the study period, 358
      thyroidectomies were performed. The indication for procedure included: FNA
      findings, n = 122; symptomatic multinodular goiter, n = 85; nodule >4 cm, n = 30;
      Graves', n = 26; other, n = 95. FNA was performed in 231 patients. Bethesda
      classification included: benign, n = 69; malignant, n = 55; follicular lesion of
      undetermined significance, n = 59; follicular neoplasm, n = 20; suspicious for
      malignancy, n = 16; nondiagnostic, n = 12. If standard GEP was performed for all
      indeterminate FNA results, it would have influenced the decision for surgery in
      68 (19 %) patients. Assuming 38 % of indeterminate FNA specimens will have benign
      results on genetic profiling, 27 patients would not have undergone thyroidectomy,
      translating into a 7.2 % decrease in overall thyroidectomy volume over a year.
      CONCLUSIONS: In an academic endocrine surgery program, the most common indication
      for thyroidectomy is an FNA result; however, standard application of GEP for all
      indeterminate thyroid FNAs would result in a minimal reduction in overall
      thyroidectomy volume.

PMID- 24435930
TI  - Biodegradable polymeric coatings on cochlear implant surfaces and their influence
      on spiral ganglion cell survival.
AB  - To improve the electrode-nerve interface of cochlear implants (CI), the role of
      poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P(4HB)) as potential coating
      matrices for CI was assessed both in vitro and in vivo in terms of degradation
      behavior and effects on spiral ganglion neurons, the main target of the
      electrical stimulation with a CI. Growth rates of fibroblasts on the polymers
      were investigated and a direct-contact test with freshly isolated spiral ganglion
      cells (SGC) was performed. In addition, the effects of the polymer degradation
      inside the inner ear were evaluated in vivo. The polymer degradation was assessed
      by use of scanning electron microscopy in combination with an energy-dispersive X
      ray analysis. In vitro, no influence of the polymers was detected on fibroblasts'
      viability and on SGC survival rate. In vivo, SGC density was decreased only 6
      months after implantation in the basal and middle turns of the cochlea in
      comparison to normal-hearing animals but not between implanted groups (coated or
      uncoated). The analysis of the electrode models showed that in vivo P(4HB) is
      characterized by a gradual degradation completed after 6 months; whereas, the
      PLLA coatings burst along their longitudinal axis but showed only little
      degradation within the same time frame. In conclusion, both polymers seem to
      justify further evaluation as possible coating for CI electrodes. Of the two
      options, due to its excellent coating adhesion/stability and optimal degradation
      behavior, P(4HB) may prove to be the more promising biodegradable polymer for
      designing a drug delivery system from the surface of CI electrodes.

PMID- 24435931
TI  - Phosphorus and carbon availability regulate structural composition and complexity
      of AM fungal mycelium.
AB  - The regulation of the structural composition and complexity of the mycelium of
      arbuscular mycorrhizal (AM) fungi is not well understood due to their obligate
      biotrophic nature. The aim of this study was to investigate the structure of
      extraradical mycelium at high and low availability of carbon (C) to the roots and
      phosphorus (P) to the fungus. We used monoxenic cultures of the AM fungus
      Rhizophagus irregularis (formerly Glomus intraradices) with transformed carrot
      roots as the host in a cultivation system including a root-free compartment into
      which the extraradical mycelium could grow. We found that high C availability
      increased hyphal length and spore production and anastomosis formation within
      individual mycelia. High P availability increased the formation of branched
      absorbing structures and reduced spore production and the overall length of
      runner hyphae. The complexity of the mycelium, as indicated by its fractal
      dimensions, increased with both high C and P availability. The results indicate
      that low P availability induces a growth pattern that reflects foraging for both
      P and C. Low C availability to AM roots could still support the explorative
      development of the mycelium when P availability was low. These findings help us
      to better understand the development of AM fungi in ecosystems with high P input
      and/or when plants are subjected to shading, grazing or any management practice
      that reduces the photosynthetic ability of the plant. 

PMID- 24435932
TI  - Comment on 'heterogeneity in action: the role of passive personalization in
      comparative effectiveness research'.

PMID- 24435933
TI  - Fasting insulin and endogenous hormones in relation to premenopausal breast
      density (Canada).
AB  - PURPOSE: Mammographic breast density (BD) is associated with increased risk of
      breast cancer. This study asks which circulating metabolic and reproductive
      biomarkers are associated with BD, particularly dense breast area, in
      premenopausal women not taking exogenous hormones. METHODS: In a cross-sectional
      study, 299 premenopausal women aged 40-49 completed questionnaires, provided a
      fasting blood sample, had height, weight, percentage body fat, waist and hip
      measurements taken, and attended a screening mammogram. Multivariate linear
      regression was used to calculate adjusted means for percentage BD, absolute dense
      and non-dense area, across categories of covariates, adjusted for day of
      menstrual cycle, age, parity, body mass index, percentage body fat, and
      ethnicity. RESULTS: Fasting insulin levels were inversely associated, and insulin
      like growth factor-binding protein 1 levels directly associated with percentage
      BD, but lost statistical significance after multivariate adjustment. Sex hormone
      binding globulin levels were directly associated with percentage BD, still
      significant after multivariate adjustment (p = 0.03). A significant inverse dose
      response association was observed between progesterone levels and dense area (p <
      0.01). CONCLUSIONS: Breast density in premenopausal women seems unrelated or
      inversely related to insulin resistance, levels of insulin-like growth factor 1
      and its binding proteins, and levels of sex steroids; therefore, the mechanism by
      which radiodensity on a mammogram is related to breast cancer risk remains
      unclear.

PMID- 24435934
TI  - Is the trend in primary penile cancer in England real?

PMID- 24435935
TI  - Reply to comments by Dr. Frisch and Dr. Van Howe.

PMID- 24435936
TI  - The association between circulating high-sensitivity C-reactive protein
      concentration and pathologic measures of colonic inflammation.
AB  - PURPOSE: C-reactive protein (CRP), an inflammation marker, is associated with
      colorectal cancer (CRC) risk in some prospective studies. Whether increased CRP
      is indicative of colonic inflammation, a possible CRC cause, or of other sources
      of inflammation (e.g., adiposity), is unknown. Thus, we evaluated the association
      between CRP and colonic mucosal measures of inflammation. METHODS: 151 adults
      undergoing colonoscopy provided a blood sample and random left- and right-side
      colonic mucosal biopsies. Height and weight were measured, and lifestyle
      information was collected. High-sensitivity C-reactive protein (hsCRP) was
      measured by immunoturbidometric assay. A gastrointestinal pathologist evaluated
      biopsies for seven colonic inflammation measures. Of 119 participants with
      complete information, 24 had an inflammatory bowel disease (IBD) history and were
      analyzed separately. We calculated the number of colonic inflammation measures
      present in both biopsies, and separately for right and left biopsies. Adjusted
      geometric mean hsCRP was calculated using linear regression, overall, by
      demographic and lifestyle factors, and inflammation measures. RESULTS: Most
      participants had >= 1 colonic inflammation measure (0: 21 %, 1: 39 %, >= 2: 40
      %). Adjusted mean hsCRP did not increase with increasing number of inflammation
      measures (0: 1.67; 1: 1.33; >= 2: 1.01 mg/L; p trend = 0.21). Obese (2.03 mg/L)
      and overweight (1.61 mg/L) participants had higher adjusted mean hsCRP than
      normal-weight participants (0.62 mg/L; p trend <0.0001). Patterns were similar
      for participants with a history of IBD. CONCLUSIONS: hsCRP concentration was not
      associated with colonic inflammation, although hsCRP increased with adiposity.
      The hsCRP-CRC association may be explained by residual confounding by other risk
      factors, such as adiposity, rather than by CRP marking colonic inflammation.

PMID- 24435937
TI  - Activation of AMP-activated protein kinase by metformin protects against global
      cerebral ischemia in male rats: interference of AMPK/PGC-1alpha pathway.
AB  - Here, we have investigated the effect of metformin pretreatment in the rat models
      of global cerebral ischemia. Cerebral ischemia which leads to brain dysfunction
      is one of the main causes of neurodegeneration and death worldwide. Metformin is
      used in clinical drug therapy protocols of diabetes. It is suggested that
      metformin protects cells under hypoxia and ischemia in non-neuronal contexts.
      Protective effects of metformin may be modulated via activating the AMP activated
      protein kinase (AMPK). Our results showed that induction of 30 min global
      cerebral I/R injury using 4-vesseles occlusion model led to significant cell
      death in the rat brain. Metformin pretreatment (200 mg kg/once/day, p.o., 2
      weeks) attenuated apoptotic cell death and induced mitochondrial biogenesis
      proteins in the ischemic rats, analyzed using histological and Western blot
      assays. Besides, inhibition of AMPK by compound c showed that metformin resulted
      in apoptosis attenuation via AMPK activation. Interestingly, AMPK activation was
      also involved in the induction of mitochondrial biogenesis proteins using
      metformin, inhibition of AMPK by compound c reversed such effect, further
      supporting the role of AMPK upstream of mitochondrial biogenesis proteins. In
      summary, Metformin pretreatment is able to modulate mitochondrial biogenesis and
      apoptotic cell death pathways through AMPK activation in the context of global
      cerebral ischemia, conducting the outcome towards neuroprotection.

PMID- 24435938
TI  - Urtica dioica extract attenuates depressive like behavior and associative memory
      dysfunction in dexamethasone induced diabetic mice.
AB  - Evidences suggest that glucocorticoids results in depression and is a risk factor
      for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal
      dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been
      used for diabetes mellitus and cognitive dysfunction. The present study
      investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50
      and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its
      associated complications such as depressive like behavior and cognitive
      dysfunction. We observed that mice administered with chronic dexamethasone
      resulted in hypercortisolemia, oxidative stress, depressive like behavior,
      cognitive impairment, hyperglycemia with reduced body weight, increased water
      intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression.
      Urtica dioica significantly reduced hyperglycemia, plasma corticosterone,
      oxidative stress and depressive like behavior as well as improved associative
      memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5
      mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and
      serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced
      hyperglycemia and its associated complications such as depressive like behavior
      and cognitive dysfunction.

PMID- 24435939
TI  - The fear-factor stress test: an ethical, non-invasive laboratory method that
      produces consistent and sustained cortisol responding in men and women.
AB  - We describe a method to administer a controlled, effective stressor to humans in
      the laboratory. The method combines the Trier Social Stress Test (TSST) and the
      Cold Pressor Test into a single, believable procedure called the Fear-Factor
      Stress Test (FFST). In the procedure, participants imagine auditioning for the
      reality television show Fear Factor. They stand before a video recorder and a
      panel of judges while (a) delivering a motivational speech, (b) performing a
      verbal arithmetic task, and (c) placing one hand into a bucket of ice water for
      up to 2 min. We measured subjective anxiety, heart rate, and salivary cortisol in
      three groups of young adults (n = 30 each, equal numbers of men and women): FFST,
      TSST, and Control (a placebo version of the FFST). Although the FFST and TSST
      groups were not distinguishable at the cortisol measure taken 5 min post
      manipulation, at 35 min postmanipulation average cortisol levels in the TSST
      group had returned to baseline, whereas those in the FFST group continued to
      rise. The proportion of individual cortisol responders (>= 2 nmol/l increase over
      baseline) in the TSST and FFST groups did not differ at the 5-min measure, but at
      the 35-min measure the FFST group contained significantly more responders. The
      findings indicate that the FFST induces a more robust and sustained cortisol
      response (which we assume is a marker of an HPA-axis response) than the TSST, and
      that it does so without increasing participant discomfort or incurring
      appreciably greater resource and time costs. 

PMID- 24435940
TI  - Subsequent risk of nasopharyngeal carcinoma among patients with allergic
      rhinitis: a nationwide population-based cohort study.
AB  - BACKGROUND: The purpose of this study was to examine the risk of nasopharyngeal
      carcinoma (NPC) after a diagnosis of allergic rhinitis. METHODS: We identified
      67,532 patients with allergic rhinitis (allergic rhinitis cohort) and a 135,064
      control cohort with the same mean age and sex ratio by using a Taiwan
      Longitudinal Health Insurance Database (LHID) sample from 2000 to 2005. RESULTS:
      After adjusting for the possible confounding factors of the study, the allergic
      rhinitis cohort had a 2.33-fold higher risk of developing NPC than did the
      comparison cohort. The frequency of allergic rhinitis visits was correlated with
      the risk of subsequent NPC. Patients with 4 or more allergic rhinitis visits per
      year were significantly associated with increasingly developing NPC risk.
      CONCLUSION: Patients with allergic rhinitis might be associated with subsequent
      NPC in Taiwan. Those who had repeated visits for allergic rhinitis had even
      higher risk for NPC. Physicians should be aware of the link when assessing
      patients with allergic rhinitis.

PMID- 24435941
TI  - Respite care for people with dementia and their carers.
AB  - BACKGROUND: Caring for someone with dementia can be emotionally and physically
      demanding. Respite care is any intervention designed to give rest or relief to
      caregivers. It is not clear what positive and negative effects such care may have
      on them, or on people with dementia. OBJECTIVES: To assess the benefits and harms
      of respite care for people with dementia and their caregivers, in particular the
      effect of respite care on rates of institutionalisation. SEARCH METHODS: The
      trials were identified from a search of ALOIS, the Specialized Register of the
      Cochrane Dementia and Cognitive Improvement Group, using the terms respite* OR
      daycare OR caregiver* relief. ALOIS contains up-to-date records from all major
      healthcare databases and many ongoing trial databases. SELECTION CRITERIA:
      Randomised controlled trials comparing respite care with a control intervention
      for people with dementia. DATA COLLECTION AND ANALYSIS: Two review authors
      carried out study selection independently and reached a consensus through
      discussion. Data were extracted by a single review author. The review authors
      contacted all investigators for methodological details not reported in the text
      and for additional data for three studies included in the previous version of the
      review. MAIN RESULTS: Four trials are now included in the review, with 753
      participants. They were different in many ways including the intervention,
      duration, outcomes and control group so pooling of data was not possible.
      Overall, the quality of the evidence was rated as very low. Re-analysis of
      outcomes using data from the published studies found no significant effects of
      respite care compared to no respite care on any caregiver variable. When respite
      care was compared to polarity therapy a significant effect was found in favour of
      polarity therapy for caregiver perceived stress (n = 38, MD 5.80, 95% CI 1.43 to
      10.17), but not for other measures of psychological health and other caregiver
      outcomes. No studies reported evaluable data on outcomes related to the people
      with dementia. AUTHORS' CONCLUSIONS: Current evidence does not demonstrate any
      benefits or adverse effects from the use of respite care for people with dementia
      or their caregivers. These results should be treated with caution, however, as
      they may reflect the lack of high quality research in this area rather than an
      actual lack of benefit. Given the frequency with which respite care is advocated
      and provided, well-designed trials are needed in this area.

PMID- 24435942
TI  - Genetic heterogeneity among the founders of laboratory populations of Drosophila
      melanogaster : V. Sternopleural and abdominal chaetae in the same strains.
AB  - 1. Single inseminated females of Drosophila melanogaster derived from the same
      population led to discrete strains for both Sternopleural and abdominal chaeta
      number in agreement with other work, which indicates that the wild populations
      have genes polymorphic for these traits. Variability varied significantly between
      strains for Sternopleural but not abdominal chaeta number. 2. Overall, the data
      show a weak correlation between the two traits. Considering this by strain, the
      correlations go from negative (but not significantly < 0) to positive (but
      significantly > 0). Therefore just as the rate of response to directional
      selection has been shown to be extremely rapid when based on strains extreme in
      the direction of the required selection response, it seems that a similar process
      may be useful for directional selection based on two traits simultaneously, by
      using only those strains showing a positive correlation. 

PMID- 24435943
TI  - [The pigment content of induced mutants of Pisum sativum as basis for a new
      method of color specification and its correlation with plastid size].
AB  - Several methods for characterizing the color of pigment mutants can be found in
      the literature. Either verbal descriptions or comparisons with a color catalogue
      are used. These methods are subjective. Furthermore, the usual classifications of
      the pigment mutants as viridis, chlorina or xantha are not clearly defined. An
      attempt was therefore made to characterize the color of different Pisum mutants
      through a mathematically calculable "Farbwert" (Color value) obtained by
      spectrophotometric pigment analysis. This value takes into account the quantity
      as well as the quality of the pigment. However, the color also depends on
      secondary factors, e.g. the size and the amount of plastids, their arrangement in
      the mesophyll, the extent of intercellular space, the waxy layer of the
      epidermis, and possible hairiness. The correlation between plastid size and
      pigment content was investigated. 

PMID- 24435944
TI  - Selection and recombination in Drosophila melanogaster.
AB  - Artificial selection for wing length in Drosophila melanogaster resulted in
      changed crossing-over frequencies between three marker genes on the 2nd
      chromosome, b, cn and vg.The results suggest that artificial selection is a
      causal agent in producing the observed changes; moreover it is suggested that the
      modifications in cross-over frequency are controlled by extra-nuclear factors. 

PMID- 24435945
TI  - Threshold concentration of plasmon-sensitive polygenes in the expression of
      quantitative characters of maize (Zea mays L.).
AB  - Reciprocal crosses between varieties of maize were developed in such a way that
      the genome of one variety was introduced into the cytoplasm of the other in
      fractions of 25, 50, and 75 per cent. Cytoplasmic effects on yield, maturity,
      plant height, and ear height were measured at each of the three nuclear
      constitutions. The results indicated that the cytoplasmic effects on quantitative
      characters were not consistently produced irrespective of the nuclear
      constitution and some relationship existed between the number of polygenes
      introduced and the cytoplasmic effects. The hypothesis was put forward that
      cytoplasmic effects on quantitative characters would be expressed only when the
      genes of one parent remained below a certain threshold concentration in the
      hybrid nucleus. Once this level was crossed by increasing the number of genes
      alien to the cytoplasm the cytoplasmic effects disappeared. 

PMID- 24435946
TI  - Genetic factors affecting maize tolerance to low temperatures at emergence and
      germination.
AB  - On the basis of the percentage of plants emerging under laboratory cold-test
      conditions, inbred lines were divided into tolerant (T), semi-tolerant (I) and
      sensitive (S) to low temperatures. Tolerance to low temperature is, then, an
      inheritable and varietal plant characteristic.On average, local varieties showed
      the best emergence, followed by double crosses, single crosses and inbred lines
      in that order. Some tolerant hybrids and inbred lines had quite high emergence
      after 27 days at 6  degrees C. Thus the tolerant inbred lines Bc-130 E-5 and T
      193/II had more emerged seeds (78 and 75% with embryo roots and 52 and 47% with
      stalk apices, respectively) with longer embryo roots and stalk apices than the
      sensitive inbred lines T-145/11 and W-8 at the end of this treatment.The two-year
      average emergence of 56 reciprocal single crosses and their parental inbred lines
      cold-tested at 6  degrees C and 8  degrees C indicates that the degree of
      tolerance to low temperatures is strongly dependent on the germination ability of
      the maternal parent of the cross, i. e. on maternal effect. The genetic mechanism
      of this inheritance is rather complex. The higher stand density of single crosses
      over inbred lines may be explained by complementary gene action in the seed
      embryo. The characteristics of the maternal parent were important in determining
      not only the percentage of germinated plants, but also the speed of germination
      and growth of the embryo root and stalk apex. With each parental inbred line the
      percentage emergence differed according to whether the line was used as the
      maternal or pollen parent in the crosses. 

PMID- 24435947
TI  - Sampling variance of the correlation coefficients estimated from analyses of
      variance and covariance.
AB  - A generalized sampling variance of correlation coefficients is derived for
      phenotypic, genetic and en vironmental correlations estimated from nested
      analyses of variance and covarianee for the equal number case. A numerical
      example is presented to estimate the sampling variance for the genetic
      correlation coefficient based on the relationship among full sibs using unequal
      subclass numbers. 

PMID- 24435948
TI  - Cytological evidence on the origin of sweet potato.
AB  - The results of intensive meiotic studies, particularly of the karyology and
      chromosomal homology at the pachytene stage, in the sweet potato (Ipomoea batatas
      L.), which is a hexaploid (2 n = 90), have thrown considerable light on its
      origin and genome relationships. Using suitable criteria, such as relative length
      of chromosomes, centromere position, chromomere pattern, absence of light
      staining segments in one of the arms, presence of telochromomere etc., 40 of the
      45 haploid chromosome complement at pachytene were identified and assigned to 19
      chromosomal types. Among these types, eight were present singly; in six of the
      types, chromosomes were present in duplicate, and in two types, in triplicate.
      The occurrence of higher multivalent chromosomal associations such as hexavalents
      and pentavalents, in addition to the quadrivalents already reported, was recorded
      for the first time at the pachytene and metaphase I stages. The hexavalents at
      pachytene were resolved into three distinct types based on the morphology of the
      participating chromosomes. A maximum number of nine quadrivalents at the
      metaphase I stage and four in the incompletely analyzed pachytene nuclei were
      recorded. The constituent chromosomes of three of the quadrivalents at pachytene
      stage were identified. From these observations, it is suggested that (i) the
      three parental genomes are partly homologous (ii) two of the genomes show closer
      homology to one another than to the third and (iii) the three genomes differ with
      respect to one or more of the eight chromosomal types occurring singly. The
      available information rules out an autopolyploid origin for sweet potato and
      suggests that the parental genomes are from closely related taxa. The advantages
      are emphasized of pursuing similar studies in other American Ipomoea species to
      unravel their relationship with the sweet potato. Among other meiotic
      irregularities, a translocated chromosome and a chromosome carrying inversion
      were detected at the pachytene stage and the possible role they may play in
      varietal differentiation is discussed. 

PMID- 24435949
TI  - The En mutable system in maize : III. Transposition associated with mutational
      events.
AB  - 1. The mutable allele, a 1 (m(pa-pu)) of the En system at the a 1 locus in maize
      mutates somatically and germinally to pale, colorless, and purple. 2. Colorless
      and pale germinal deviants arise at a high frequency. The colorless is more
      frequent than the pale, and each is more frequent than purple. Frequency is
      correlated with timing of the somatic mutation event - the earlier colorless
      sectoring is correlated with the higher frequency of colorless deviants. 3. The
      regulatory element, En, has been identified at the a 1 locus. The origin of
      colorless and pale deviants is accompanied by the transposition of an En element
      away from the a 1 site. 4. The transposing event may lead to implantation of En
      on the same chromosome, on another chromosome, or no implantation occurs.
      Transposition to a linked site occurs approximately 25% of the time. There is a
      preference for transposition to sites 6-20 units from a 1. 5. Secondary
      transpositions of En occur, and in one test, approximately 12% of the time, to an
      independent position. Secondary transpositions take place to new linked sites. 6.
      Preliminary data indicate that transpositions can occur to both distal and
      proximal positions on chromosome 3. 7. Since differences exist in the behaviour
      of elements in transposition, it is likely that the transposition event probably
      is dependent on the elements of specific mutable systems and differing elements
      within a system. 8. Theoretical aspects of diverse types of impairment of normal
      gene function by inserted elements is discussed. 

PMID- 24435950
TI  - Forensic animal DNA analysis using economical two-step direct PCR.
AB  - Wildlife forensic DNA analysis by amplification of a mitochondrial locus followed
      by DNA sequencing is routine, yet suffers from being costly and time-consuming.
      To address these disadvantages we report on a low-cost two-step direct PCR assay
      to efficiently analyze 12 forensically relevant mammalian sample types without
      DNA extraction. A cytochrome oxidase I degenerate-universal primer pair was
      designed and validated for the developed assay. The 12 sample types, which
      included bone, horn, feces, and urine, were amplified successfully by the assay
      using a pre-direct PCR dilution protocol. The average amplification success rate
      was as high as 92.5 % (n = 350), with an average PCR product concentration of
      220.71 +/- 180.84 ng/MUL. Differences in amplification success rate and PCR
      product quantity between sample types were observed; however, most samples
      provided high quality sequences, permitting a 100 % nucleotide similarity to
      their respective species via BLAST database queries. The combination of PBS and
      Phire((r)) Hot Start II DNA polymerase gave comparable amplification success rate
      and amplicon quantity with the proprietary commercial kits (P > 0.05, n = 350)
      but at considerably lower cost. The stability of the assay was tested by
      successfully amplifying samples that had been stored for up to 12 months. Our
      data indicate that this low-cost two-step direct amplification assay has the
      potential to be a valuable tool for the forensic DNA community.

PMID- 24435951
TI  - Unusual genital piercing dividing the corpora cavernosa.

PMID- 24435952
TI  - Sudden unexpected infant deaths associated with car seats.
AB  - The purpose of this study was to investigate the frequency, circumstances,
      demographics, and causes of death of infants dying while seated in car safety
      seats. A retrospective review of a pediatric autopsy database at a specialist
      center over a 16-year period was undertaken to identify any infant deaths (aged
      <1 year), in whom death occurred while seated in a car safety seat. Fourteen car
      seat-associated deaths were identified from a total of 1,465 coronial infant
      autopsies (0.96 %). Four involved infants were being appropriately transported in
      the car seat, all of whom had a medical underlying cause of death (one infection
      and three congenital heart disease). The majority (10 cases; 70 %) occurred while
      car seats were being inappropriately used, outside of the car, including as an
      alternative to a cot or high-chair. Five of these infants died of explained
      causes, but four deaths remained unexplained after autopsy, and in one no cause
      of death was available. There were no cases of previously healthy infants dying
      unexpectedly in a car seat when it was being used appropriately, and in this
      series there were no cases of traumatic death associated with car seats, either
      during road traffic accidents, or from falling or being suspended from a car
      seat. Infant deaths in car seats are rare. These data support the recommendation
      that car seats be used only for transport and not as alternatives for cots or
      high-chairs. More research is required to investigate the effect of travel in car
      seats on infants with underlying conditions. There appears to be no increased
      risk of unexpected deaths of healthy infants transported appropriately in car
      seats. 

PMID- 24435953
TI  - Cardiac tumors and sudden death.

PMID- 24435954
TI  - Testing for antiphospholipid antibodies at autopsy.

PMID- 24435955
TI  - MyD88 signalling in myeloid cells is sufficient to prevent chronic mycobacterial
      infection.
AB  - Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis
      that is responsible for almost 1.5 million deaths per year. Sensing of
      mycobacteria by the host's immune system relies on different families of
      receptors present on innate immune cells. Amongst them, several members of the
      TLR family are involved in the activation of immune cells by mycobacteria, yet
      the in vivo contribution of individual TLRs to the protective immune response
      remains controversial. On the contrary, MyD88, the adaptor molecule for most
      TLRs, plays a non-redundant role in the protection against tuberculosis and mice
      with a complete germline deletion of MyD88 succumb very early to infection. MyD88
      is expressed in both immune and non-immune cells, but it is not clear whether
      control of mycobacteria requires ubiquitous or cell-type specific MyD88
      expression. Therefore, using novel conditional switch-on mouse models, we aimed
      to investigate the importance of MyD88 signalling in DCs and macrophages for the
      induction of protective effector mechanisms against mycobacterial infection. We
      conclude that specific reactivation of MyD88 signalling in CD11c- or lysozyme M
      expressing myeloid cells during Mycobacterium bovis Bacille Calmette-Guerin
      infection is sufficient to restore systemic and local inflammatory cytokine
      production and to control pathogen burden. 

PMID- 24435956
TI  - Accelerated whole-heart coronary MRA using motion-corrected sensitivity encoding
      with three-dimensional projection reconstruction.
AB  - PURPOSE: To achieve whole-heart coronary magnetic resonance angiography (MRA)
      with (1.0 mm)(3) spatial resolution and 5 min of free-breathing scan time.
      METHODS: We used an electrocardiograph-gated, T2-prepared and fat-saturated
      balanced steady state free precession sequence with 3DPR trajectory for free
      breathing data acquisition with 100% gating efficiency. For image reconstruction,
      we used a self-calibrating iterative SENSE scheme with integrated retrospective
      motion correction. We performed healthy volunteer study to compare the proposed
      method with motion-corrected gridding at different retrospective undersampling
      levels on apparent signal-to-noise ratio (aSNR) and subjective coronary artery
      (CA) visualization scores. RESULTS: Compared with gridding, the proposed method
      significantly improved both image quality metrics for undersampled datasets with
      6000, 8000, and 10,000 projections. With as few as 10,000 projections, the
      proposed method yielded good CA visualization scores (3.02 of 4) and aSNR values
      comparable to those with 20,000 projections. CONCLUSION: Using the proposed
      method, good image quality was observed for free breathing whole-heart coronary
      MRA at (1.0 mm)(3) resolution with an achievable scan time of 5 min.

PMID- 24435958
TI  - Thermal lens microscopy as a detector in microdevices.
AB  - The small length scales that make microfluidics attractive are also the source of
      some very stringent constraints, especially with respect to the detection
      approach used. The low concentrations often analyzed in microfluidic devices
      require highly sensitive detection methods that are effective even in vanishingly
      small sample volumes. Over the years, many detection approaches have been
      developed for microfluidics. The majority of these methods rely upon optical
      phenomena, with the most common being fluorescence detection. Fluorescence
      detection is well suited to microfluidics because it is both flexible and
      sensitive; however, it does have shortcomings. Weak fluorescence of targets,
      autofluorescence of materials, and photobleaching are a few of the issues that
      have to be dealt with when working with fluorescence detection. Another option
      that eliminates all of these problems is thermal lens microscopy (TLM), a
      photothermal spectroscopy technique. TLM is a flexible, sensitive detection
      approach for nonfluorescent molecules that is capable of carrying out single
      molecule detection to label-free in vivo quantification. Despite the potential
      benefits of TLM, it is still an underutilized detection approach. We hope this
      review will help broaden the use of TLM for microchip-based CE, as well as a host
      of other microfluidic applications. 

PMID- 24435957
TI  - Parvalbumin and calbindin expression in parallel thalamocortical pathways in a
      gleaning bat, Antrozous pallidus.
AB  - The pallid bat (Antrozous pallidus) listens to prey-generated noise to localize
      and hunt terrestrial prey while reserving echolocation to avoid obstacles. The
      thalamocortical connections in the pallid bat are organized as parallel pathways
      that may serve echolocation and prey localization behaviors. Thalamic inputs to
      the cortical echolocation call- and noise-selective regions originate primarily
      in the suprageniculate nucleus (SG) and ventral division of medial geniculate
      body (MGBv), respectively. Here we examined the distribution of parvalbumin (PV)
      and calbindin (CB) expression in cortical regions and thalamic nuclei of these
      pathways. Electrophysiology was used to identify cortical regions selective for
      echolocation calls and noise. Immunohistochemistry was used to stain for PV and
      CB in the auditory cortex and MGB. A higher percentage (relative to Nissl-stained
      cells) of PV(+) cells compared with CB(+) cells was found in both echolocation
      call- and noise-selective regions. This was due to differences in cortical layers
      V-VI, but not layers I-IV. In the MGB, CB(+) cells were present across all
      divisions of the MGB, with a higher percentage in the MGBv than the SG. Perhaps
      the most surprising result was the virtual absence of PV staining in the MGBv. PV
      staining was present only in the SG. Even in the SG, the staining was mostly
      diffuse in the neuropil. These data support the notion that calcium binding
      proteins are differentially distributed in different processing streams. Our
      comparative data, however, do not support a general mammalian pattern of PV/CB
      staining that distinguishes lemniscal and nonlemniscal pathways.

PMID- 24435959
TI  - Polycyclic aromatic hydrocarbon body residues and lysosomal membrane
      destabilization in mussels exposed to the Dubai Star bunker fuel oil
      (intermediate fuel oil 380) spill in San Francisco Bay.
AB  - Following the spill of bunker fuel oil (intermediate fuel oil 380, approximately
      1500-3000 L) into San Francisco Bay in October 2009, polycyclic aromatic
      hydrocarbon (PAH) concentrations in mussels from moderately oiled areas increased
      up to 87 554 ng/g (dry wt) and, 3 mo later, decreased to concentrations found in
      mussels collected prior to oiling, with a biological half-life of approximately
      16 d. Lysosomal membrane destabilization increased in mussels with higher PAH
      body burdens.

PMID- 24435960
TI  - Early detachment of the Solitaire stent during thrombectomy retrieval: an in
      vitro investigation.
AB  - OBJECTIVE: To elucidate the early detachment of the Solitaire stent during
      mechanical thrombectomy, we tested the stent in vitro under various conditions
      and evaluated with microscopy. METHODS: A total of five stents were tested. Using
      a dynamic mechanical analysis machine, we calculated the tensile force needed for
      separation of the four stents from the pusher wire. Stent Nos 1 and 2 were tested
      without any prior manipulation. During the retraction test, no sheathing around
      the stent-wire junction was applied to stent No 1 whereas stent No 2 was
      partially covered with a sheath in accordance with instructions for use (IFU)
      recommendations. Stent No 3 was tested after deployment and retrieval were
      performed three times in an in vitro vascular replica with sheathing during
      retrieval. Stent No 4 was tested after one deployment and retrieval using the
      same replica as in stent No 3 without sheathing. In addition, forward pushing
      force was applied intentionally during retraction to induce excessive bending of
      the stent. Stent No 5 was pulled apart by both hands. After separation, stent
      tips and pusher wires were studied for all stents under the microscope. RESULTS:
      The tensile force needed for separation was about 6 N for stent Nos 1, 2, and 3,
      and about 4 N for stent No 4. All of the stents showed separation at the proximal
      marker, not at the detachment zone. CONCLUSIONS: Detachment of the Solitaire
      stent during thrombectomy can be due to separation around or inside the proximal
      marker. Adherence to the manufacturer's IFU of partial re-sheathing during
      retraction and not using the device for more than two passes might decrease the
      possibility of such device failure.

PMID- 24435962
TI  - Cortical cell fluxes and transport to the stele in excised root segments of
      Allium cepa L. : I. Potassium, sodium and chloride.
AB  - From compartmental analysis of radioisotope elution measurements, concentrations
      and fluxes of K(+), Na(+) and Cl(-) were estimated for cortical cells in root
      segments of onion, Allium cepa L., relative to a complete nutrient solution. The
      transported fraction of the total efflux was estimated separately. With the
      Ussing-Teorell flux ratio equation as the criterion, it was concluded that all
      three ions were actively accumulated from the outside medium into the cytoplasm
      and that only Na(+) was actively accumulated into the vacuole. K(+) and Cl(-)
      moved passively, in both directions across the tonoplast. Failure to account for
      leakage from the stele via the segment cut ends resulted in an over-estimate of
      exchange across the tonoplast but did not alter the conclusions qualitatively.
      The consequences of changing the assumed value of the tonoplast electrical
      potential (from 0 to+10- mV), and the effects of different experimental
      procedures, were also assessed, and found not to affect the main conclusions
      significantly. Separate measurement of ions leaking from the segment ends
      revealed that Na(+) was transported almost exclusively in an acropetal direction
      in the stele. Cl(-) appeared at both ends of the segments in similar amounts and
      K(+) was transported mainly in the basipetal direction. The implications of these
      findings for the mechanism and site of ion selectivity are discussed. 

PMID- 24435963
TI  - Cortical cell fluxes and transport to the stele in excised root segments of
      Allium cepa L. : II. Calcium.
AB  - From compartmental analysis of radioisotope elution measurements, concentrations
      and fluxes of Ca(2+) were estimated for cortical cells in root segments of onion,
      Allium cepa L., relative to a complete nutrient solution containing 1 mM Ca(2+).
      Five compartments for Ca(2+) in the cortex were revealed. These were identified,
      in order of increasing rates of exchange, with the vacuole and cytoplasm of the
      cortical parenchyma, the Donnan free space in the cell walls, the water free
      space in the tissue and the superficial film of solution on the segments. With
      the Ussing-Teorell flux ratio equation as the criterion, it was concluded that
      Ca(2+) entered the cytoplasm passively and was actively pumped back to the
      external solution. Ca(2+) concentration in the vacuole could only be estimated as
      lying between wide limits (1.0 to 7.5 MUeq. ml(-1)), but even at the maximum
      concentration, it was concluded that entry was passive and content limited by an
      efflux pump across the tonoplast. Net flux was zero and the vacuolar
      concentration of Ca(2+) compatible with this was found to be 2.6 MUeq. ml(-1).
      The transported fraction of the total efflux, appearing at the segment cut ends,
      was estimated separately. Calcium was found to be transported almost exclusively
      in the basipetal direction. 

PMID- 24435964
TI  - The influence of light, darkness, and lack of CO2 on phloem translocation in
      detached maize leaves.
AB  - Longitudinal strips from leaf blades of Zea mays L., with veins continuous along
      their whole length, proved to be a very uniform and convenient material for
      translocation experiments. Under normal photosynthetic conditions a very strong
      basipetal assimilate movement was shown. In the dark this movement persisted as
      long as starch reserves were available. Parts of the strips exposed to darkness
      or to CO2-free air, i.e. nonphotosynthetic conditions, became strong sinks which
      attracted assimilates, darkness having the strongest effect. Microradioautographs
      showed that transport of assimilates took place in the sieve tubes of the phloem.

PMID- 24435965
TI  - The use of compartmental analysis in the study of the movement of carbon through
      leaves.
AB  - The export of (14)C from leaves of Lycopersion esculentum (Mill.), Capsicum
      frutescens (L.) and Amaranthus caudatus (L.) was followed by in vivo counting
      after exposure of the leaf to a 5 min pulse of (14)CO2. In all instances the time
      course of export showed two or more exponential phases. There was an initial
      rapid period of export which was followed by a slower phase after about 2 h.
      About 12-14 h after exposure to (14)CO2 this second phase was superseded by an
      even slower phase of export which continued for more than 24 h. In tomatoes the
      initial phase was most rapid in plants bearing fruit which had been heated to 30
      degrees C instead of the standard 15-20 degrees C; it was slowest when the fruit
      were removed. In Amaranthus the rate of the initial phase was shown to be
      positively correlated with photosynthesis and when the latter was prevented by
      either darkness or the absence of CO2 the rate of loss of (14)C was reduced. The
      data were used to test a model of carbon movement from a leaf which postulated
      the presence of two carbon pools which turned-over at different rates. The
      photosynthetic carbon entered the pool with the faster rate of turn-over-the
      'labile' pool-and exchanged with the other, 'storage', pool. Export from the leaf
      was from the 'labile' pool. The results suggested that a third, longer term,
      storage pool should be included in the model and that the exchange between the
      pools should be non-linear. 

PMID- 24435966
TI  - On the heat-pulse method for the measurement of apparent sap velocity in stems.
AB  - The velocity of a heat pulse moving through the xylem of a stem is generally not
      the same as the sap velocity. One can measure the sap velocity by carefully
      characterizing the shape of such a pulse. In much contemporary work the phase
      relations of sap flow are more important than the actual velocity. It is shown
      that the measurement of the time for the peak of a heat pulse to reach a sensor
      can characterize an "apparent heat-pulse velocity". A theoretical analysis shows
      that this velocity is expected to be in phase with the sap velocity.A temperature
      compensated system for the measurement of apparent sap velocity in the stem of a
      cotton plant is presented. Output variations caused by changes in the ambient air
      temperature are eliminated through use of opposing thermistors in a bridge
      circuit. One thermistor was used as a sensor while the other served as
      compensator for ambient temperature changes. 

PMID- 24435967
TI  - The pattern of development of Anabaena in the Azolla-Anabaena symbiosis.
AB  - The development of Anabaena in the leaf cavities of Azolla (probably A.
      filiculoides) was studied. After the alga is installed in the cavity, heterocyst
      frequency rises to a maximum (20-30%) about 12 leaves from the apex, then remains
      constant until the leaf senesces. The size of vegetative cells of the alga
      increases with cell width apparently increasing linearly with increasing leaf
      age. 

PMID- 24435968
TI  - [On the mechanism of action of glutamate dehydrogenase from pea seedlings and the
      regulation of the activity by adenosine phosphates, the energy charge and ions].
AB  - The mechanism of action and the regulatory properties of glutamate dehydrogenase
      from pea seedlings (Pisum sativum, var. Spaths Violetta) have been investigated
      by using a highly purified preparation of the enzyme. Kinetic experiments show
      that the binding of the coenzyme (NAD(+) or NADH) and the substrate (L-glutamate
      or alpha-ketoglutarate) is sequential. The formation of a quarternary complex
      with ammonia as additional substrate is questionable, as can be seen from the
      kinetic data. The anions of the ammonia source have a strong rate-regulating
      effect on the NADH reaction. The adenosinphosphates AMP, ADP, and ATP exert an
      inhibiting effect on both the reductive amination and the oxidative deamination
      reaction. The former reaction is inhibited half as much as the latter. Dead end
      inhibition offers a sufficient explanation for this effect. The glutamate
      dehydrogenase from pea seedlings is not regulated by the energy charge. Zn(2+)
      ions are strong inhibitors of the NADH-reaction; their inhibitory effect on the
      activity is indirect and can be reversed by addition of ATP. A reaction sequence
      is formulated. 

PMID- 24435969
TI  - Separation of cytokinins by High Pressure Liquid Chromatography.
AB  - A number of cytokinin reference compounds have been successfully separated by
      High Pressure Liquid Chromatography using columns of pellicular strong cation
      exchange resin and of pellicular polyamide. On polyamide, all cytokinins were
      eluted within 10 min with an aqueous buffer but on the cation exchange resin some
      cytokinins (generally those with bulky N(6)-substituents and in addition lacking
      an N(9)-ribosyl substituent) had excessively long retention times with aqueous
      buffer eluent. However, addition of methanol to the buffer enabled these
      cytokinins to be separated and eluted within a reasonable time. As small an
      amount as 5 nanogram of cytokinin could readily be detected by the procedures
      described. 

PMID- 24435970
TI  - Direct Determination of pH in the stomatal complex of Commelina.
AB  - The vacuolar pH of individual cells of the epidermis of intact leaves of
      Commelina communis L. has been determined using pH sensitive microelectrodes. The
      results show that the pH of the guard cells increases by approximately 0.5 units
      during stomatal opening. The changes in vacuolar pH mirror the changes in
      vacuolar potassium concentration that occur during stomatal movements. 

PMID- 24435971
TI  - Erratum.

PMID- 24435972
TI  - Expression and identification of a novel gene Spata34 in mouse spermatogenic
      cells.
AB  - Leucine-rich repeat (LRR) containing proteins play an essential role in signal
      transduction, cell adhesion, cell development, DNA repair and RNA processing.
      Here we cloned a novel gene, Spata34, encoding a LRR containing protein of 415
      aa. Spata34 gene consisted of 9 exons and 8 introns and mapped to chromosome
      3qA3. Spata34 is conserved across species in evolution. The Spata34 gene was
      expressed at various levels, faintly before first weeks postpartum and strongly
      from 2 weeks postpartum in adult testes. Western blot analysis showed that
      Spata34 protein was specially expressed in mouse testis. Immunohistochemical
      analysis revealed that Spata34 protein was most abundant in the cytoplasm of
      round spermatids and elongating spermatids within seminiferous tubules of the
      adult testis. Overexpression of Spata34 in COS7 cells inhibited the
      transcriptional activity of AP-1, p53 and p21 which suggested that Spata34
      protein may act as a transcriptional repressor in p53 and p21 pathway. 

PMID- 24435973
TI  - Association between type 2 diabetes mellitus-related SNP variants and obesity
      traits in a Saudi population.
AB  - Obesity, commonly measured as body mass index (BMI), has been on a rapid rise
      around the world and is an underlying cause of several chronic non-communicable
      diseases, including type 2 diabetes mellitus (T2DM). In addition to the
      environmental factors, genetic factors may also contribute to the ongoing obesity
      epidemic in Saudi Arabia. This study investigated the association between
      variants of 36 previously established T2DM SNPs and obesity phenotypes in a
      population of Saudi subjects. Study subjects consisted of 975 obese (BMI: >=30),
      825 overweight (25-30) and 423 lean controls (18-25) and of these 927 had a
      history of T2DM. Subjects were genotyped for 36 SNPs, which have been previously
      proved to be T2DM linked, using the KASPar method and the means of BMI and waist
      circumference (WC) corresponding to each of the genotypes were compared by
      additive, recessive and dominant genetic models. Five and seven of 36 T2DM
      related SNPs were significantly associated with the BMI and WC, respectively.
      Variants of SNPs rs7903146, rs1552224 and rs11642841 in the control group and
      rs7903146 in T2DM group showed significant association with both BMI and WC.
      Variant of SNP rs10440833 was significantly associated with BMI in T2DM group of
      both males [OR = 1.8 (1.0, 3.3); P = 0.04] and females [OR = 2.0 (1.0, 3.9); P =
      0.04]. Genetic risk scores explained 19 and 14% of WC and hip size variance in
      this population. Variants of a number of established T2DM related SNPs were
      associated with obesity phenotypes and may be significant hereditary factors in
      the pathogenesis of T2DM.

PMID- 24435974
TI  - Characterization of immune response elicited by the recombinant outer membrane
      protein OmpF of Aeromonas hydrophila, a potential vaccine candidate in murine
      model.
AB  - Porins, the outer membrane proteins of gram negative bacteria, perform vital
      roles in bacterial survival and virulence, such as nutrient transportation across
      the membrane as well as adhesion to host cells during infection. The outer
      membrane proteins, OmpF and OmpC, are part of a two-component regulatory system,
      essential for the maintenance of solute concentrations in the cytoplasmic milieu
      of bacteria, and are thus considered vital for bacterial survival. Exposed on the
      surface of gram-negative bacteria, these channel proteins are highly immunogenic
      and can thus be exploited as vaccine candidates. In the present study, we have
      cloned, characterized, and expressed outer membrane protein OmpF of Aeromonas
      hydrophila, a major fish pathogen and also known to cause severe infections in
      humans. The cloned ompF gene of A. hydrophila consisting of an open reading frame
      corresponding to mature OmpF was expressed and purified from the heterologous
      host, E. coli. High level of expression resulted in recovery of ~120 mg/L of the
      purified rOmpF at shake flask level. Polyclonal antisera raised against the
      recombinant OmpF showed a very high endpoint titer (>1:80,000) and were able to
      specifically agglutinate live A. hydrophila. Further, anti-OmpF antisera cross
      reacted with the cell lysates of various Aeromonas isolates, suggesting that anti
      rOmpF antibodies can be used to identify different A. hydrophila isolates in
      infected conditions. Antibody isotyping, cytokine ELISA, and ELISPOT assay
      indicated predominantly Th1 type of immune response. The recombinant OmpF
      reported in the present study thus has the potential to be used as a vaccine
      candidate against A. hydrophila. 

PMID- 24435975
TI  - p53 signaling pathway polymorphisms associated to recurrent pregnancy loss.
AB  - The p53 protein is known for performing essential functions in the maintenance of
      genomic stability in somatic cells and prevention of tumor formation. Studies of
      the p53 signaling pathway have suggested associations between some polymorphisms
      and infertility, post-in vitro fertilization implantation failure and recurrent
      abortions. The TP53 Pro72Arg polymorphism has been implicated as a risk factor
      for recurrent pregnancy loss (RPL); however, the association is controversial. In
      this study, our objective was to evaluate selected polymorphisms in genes of the
      p53 signalling pathway [TP53 c.215G>C (Pro72Arg), MDM2 c.14+309T>G (SNP309) and
      LIF c.1414T>G in the region 3' UTR] and determine their effect as risk factors
      for RPL. In a case-control study, we investigated 120 women with two or more
      pregnancy losses and 143 fertile control women reporting at least two live births
      and no history of pregnancy loss. When analyzed separately, the allele and
      genotype distributions of the polymorphisms in the two groups were not different.
      However, in a multivariate analysis adjusted for alcohol consumption, smoking,
      ethnicity, and number of pregnancies, the interaction between the genotypes TP53
      Arg/Arg (rs1042522) and MDM2 TT (rs2279744) showed to be associated to RPL,
      increasing the risk for this condition (OR = 2.58, 95% CI: 1.31-5.07, p = 0.006).
      In conclusion, our study indicates that the combination of TP53 Arg/Arg
      (rs1042522) and MDM2 TT (rs2279744) genotypes may be a risk factor for RPL.

PMID- 24435976
TI  - Localization of angiotensin-II type 1(AT1) receptors on buffalo spermatozoa: AT1
      receptor activation during capacitation triggers rise in cyclic AMP and calcium.
AB  - The purpose of this study was to determine the role of Ang-II in buffalo
      spermatozoa; localize angiotensin type 1 (AT1) receptors on the sperm surface and
      understand the signaling mechanisms involved therein. Immunoblotting and
      immunocytochemistry using polyclonal Rabbit anti-AT1 (N-10) IgG were performed to
      confirm the presence of AT1 receptors. Intracellular levels of cyclic adenosine
      monophosphate (cAMP) were determined by non-radioactive enzyme immunoassay, while
      that of Calcium [Ca(2+)] were estimated by fluorimetry using Fura2AM dye. The
      results obtained showed that AT1 receptors were found on the post-acrosomal
      region, neck and tail regions. Immunoblotting revealed a single protein band with
      molecular weight of 40 kDa. Ang-II treated cells produced significantly higher
      level of cAMP compared to untreated cells (22.66 +/- 2.4 vs. 10.8 +/- 0.98
      pmol/10(8) cells, p < 0.01). The mean levels of Ca(2+) were also higher in Ang-II
      treated cells compared to control (117.4 +/- 6.1 vs. 61.15 +/- 4.2 nmol/10(8)
      cells; p < 0.01). The stimulatory effect of Ang-II in both the cases was
      significantly inhibited in the presence of Losartan (AT1 antagonist; p < 0.05)
      indicating the involvement of AT1 receptors. Further, presence of neomycin
      (protein kinase C inhibitor) inhibited significantly the Ang-II mediated rise in
      Ca(2+) indicating the involvement of PKC pathway. These findings confirm the
      presence of AT1 receptors in buffalo spermatozoa and that Ang-II mediates its
      actions via the activation of these receptors. Ang-II stimulates the rise in
      intracellular levels of cAMP and Ca(2+) during capacitation.

PMID- 24435977
TI  - The role of plasma IDO activity as a diagnostic marker of patients with
      colorectal cancer.
AB  - High levels of indoleamine 2,3-dioxygenase (IDO) are involved in tumour escape
      mechanisms. The aim of this study is the evaluation of L-kynurenine of plasma as
      marker of diagnostic and prognostic in patients with colorectal cancer. The study
      included 78 patients with colorectal cancer, of whom 15 % were in stage I/II, 30
      % in stage III, and 55 % in stage IV, and was compared with a control group of 70
      healthy subjects. The receiver operating characteristic (ROC) curve analysis
      showed an area under the curve of 0.917, with a specificity of 100 % and with a
      sensitivity to detect cancer of the colon of 85.2 %, taking 1.83 MUM as a cut-off
      point. The overall survival analysis also indicated that patients with low levels
      of L-kynurenine in plasma increased survival rate after 45 months of follow-up (P
      = 0.032). These results show that the plasma levels of L-kynurenine could be a
      good biomarker to differentiate individuals with colorectal cancer from healthy
      individuals.

PMID- 24435978
TI  - hOGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis.
AB  - The Ser326Cys polymorphism in the human 8-oxogunaine glycosylase (hOGG1) gene
      with lung cancer susceptibility had been investigated by the approaches of PCR
      RFLP, PCR-SSCP and ASA. Due to limited specimen and different approaches the
      conclusion was drawn toughly. To evaluate this correlation comprehensively, a
      meta-analysis was performed based on 30 case-control studies, including 10,327
      cases and 12,148 controls. The random-effects model was used to estimate the odds
      ratios and 95 % confidence interval for various contrasts of this polymorphism.
      The combined results suggested that the hOGG1 Ser326Cys polymorphism was not
      associated with lung cancer susceptibility in different genetic models.
      Similarly, in the stratified analyses by ethnicity and source of control, no risk
      was observed between all the genetic models and lung cancer risk. Our meta
      analysis revealed that there was little correlation between the hOGG1 Ser326Cys
      polymorphism and the risk of lung cancer.

PMID- 24435980
TI  - Synergistic effects of Lewis bases and substituents on the electronic structure
      and reactivity of boryl radicals.
AB  - Boryl radicals have the potential for the development of new molecular entities
      and for application in new radical reactions. However, the effects of the
      substituents and coordinating Lewis bases on the reactivity of boryl radicals are
      not fully understood. By using first-principles methods, we investigated the spin
      density distribution and reactivity of a series of boryl radicals with various
      substituents and Lewis bases. The substituents, along with the Lewis bases, only
      affect the radical reactivity when an unpaired electron is in the boron pz
      orbital, that is, for three-coordinate radicals. We found evidence of synergistic
      effects between the substituents and the Lewis bases that can substantially
      broaden the tunability of the reactivity of the boryl radicals. Among Lewis
      bases, pyridine and imidazol-2-ylidene show a similar capacity for stabilization
      by delocalizing the spin density. Electron-donating substituents, such as
      nitrogen, more efficiently stabilize boryl radicals than oxygen and carbon atoms.
      The reactivity of a boryl radical is always boron based, irrespective of the spin
      density on boron. 

PMID- 24435979
TI  - uORF, a regulatory mechanism of the Arabidopsis polyamine oxidase 2.
AB  - The translational efficiency of an mRNA can be modulated by elements located in
      the 5'-untranslated region. The flavin-containing polyamine oxidases catabolize
      oxidative deamination of spermidine and spermine, thus contributing to polyamine
      homeostasis as well as diverse biological processes through their reaction
      products. In this study, we characterized the uORF of AtPAO2 gene using the GUS
      reporter gene. Transgenic lines harboring the native AtPAO2 promoter or the
      constitutive CaMV 35S promoter show that the uORF negatively affects GUS
      expression. Exogenous applications of PAs positively modulate GUS expression,
      thus alleviating the negative effect of AtPAO2 uORF, while treatments with MGBG
      inhibitor show an opposite effect. Our data suggest that AtPAO2 uORF regulatory
      mechanism is modulated by polyamines. In addition, we present a comparative in
      silico study of the uORFs identified in several plant transcripts encoding
      polyamine oxidases in both mono- and dicotyledonous plants as well as in the
      Bryophyte Physcomitrella patens. The polyamine oxidase uORF-encoded peptides are
      conserved among families and share conserved features such as their position,
      length, and amino acid sequence. Our findings provide new insights into the
      regulatory mechanism of polyamine oxidase genes and encourage further exploration
      to assess the biological significance of uORFs in the polyamine catabolic
      pathway.

PMID- 24435981
TI  - A national comparison of burnout and work-life balance among internal medicine
      hospitalists and outpatient general internists.
AB  - BACKGROUND: General internists suffer higher rates of burnout and lower
      satisfaction with work-life balance than most specialties, but the impact of
      inpatient vs outpatient practice location is unclear. METHODS: Physicians in the
      American Medical Association Physician Masterfile were previously surveyed about
      burnout, depression, suicidal ideation, quality of life, fatigue, work-life
      balance, career plans, and health behaviors. We extracted and compared data for
      these variables for the 130 internal medicine hospitalists and 448 outpatient
      general internists who participated. Analyses were adjusted for age, sex, hours
      worked, and practice setting. RESULTS: There were 52.3% of the hospitalists and
      54.5% of the outpatient internists affected by burnout (P = 0.86). High scores on
      the emotional exhaustion subscale (43.8% vs 48.1%, P = 0.71) and on the
      depersonalization subscale (42.3% vs 32.7%, P = 0.17) were common but similar in
      frequency in the 2 groups. Hospitalists were more likely to score low on the
      personal accomplishment subscale (20.3% vs 9.6%, P = 0.04). There were no
      differences in symptoms of depression (40.3% for hospitalists vs 40.0% for
      outpatient internists, P = 0.73) or recent suicidality (9.2% vs 5.8%, P = 0.15).
      Rates of reported recent work-home conflict were similar (48.4% vs 41.3%, P =
      0.64), but hospitalists were more likely to agree that their work schedule leaves
      enough time for their personal life and family (50.0% vs 42.0%, P = 0.007).
      CONCLUSIONS: Burnout was common among both hospitalists and outpatient general
      internists, although hospitalists were more satisfied with work-life balance. A
      better understanding of the causes of distress and identification of solutions
      for all internists is needed.

PMID- 24435982
TI  - Does age affect the response of pelvis and spine to simulated leg length
      discrepancies? A rasterstereographic pilot study.
AB  - PURPOSE: The purpose of this study was to investigate age differences in the
      response of the spine and pelvis to simulated leg length inequalities (LLIs).
      METHODS: A total of 107 subjects, separated into three age groups (group 1: 20-39
      years, group 2: 40-59 years, group 3: >60 years), were used to evaluate for any
      age effects in the response to LLIs. LLIs of +10, +20, and +30 mm were simulated
      with a simulation platform on both sides, and the respective changes of pelvic
      position (pelvic obliquity, pelvic torsion) and spinal posture (lateral
      deviation, surface rotation, kyphotic, and lordotic angles) were measured with a
      rasterstereographic system. RESULTS: In all three age groups an increase in LLI
      led to significant changes in the pelvic position as measured by the parameters
      of pelvic obliquity and torsion. No significant differences in the response of
      the pelvis to the LLIs were found between the age groups. In all age groups an
      increase in surface rotation and lateral deviation of the spine with increasing
      LLIs was found. However, none of these parameters responded significantly
      different between the three age groups. CONCLUSIONS: Under static conditions,
      LLIs lead to significant changes of the pelvic position and spinal posture.
      Despite all known age-related changes, no significant differences of the measured
      pelvic and spinal parameters in elderly patients as a response to the simulated
      LLIs occurred.

PMID- 24435983
TI  - Comment on Williams NH, et al.: a systematic review and meta-analysis of
      biological treatments targeting tumour necrosis factor alpha for sciatica (Eur
      Spine J, 2013;22(9):1921-35).

PMID- 24435984
TI  - Letter regarding Liu et al.'s study entitled "A systematic review with meta
      analysis of posterior interbody fusion versus posterolateral fusion in lumbar
      spondylolisthesis".

PMID- 24435985
TI  - Answer to the Letter to the Editor of Gui-Tao Li et al. concerning: "A systematic
      review and meta-analysis of biological treatments targeting tumour necrosis
      factor alpha for sciatica" by Williams NH, Lewis R, Din NU, Matar HE, Fitzsimmons
      D, Phillips CJ, Sutton A, Burton K, Hendry M, Nafees S, Wilkinson C (2013) Eur
      Spine J; 22:1921-1935.

PMID- 24435986
TI  - Induction of adipocyte hyperplasia in subcutaneous fat depot alleviated type 2
      diabetes symptoms in obese mice.
AB  - OBJECTIVE: The role of subcutaneous adipose tissue (SAT) in the pathogenesis of
      type 2 diabetes is still under controversy. In this study, the metabolic effects
      of inducing adipocyte hyperplasia in SAT depots in obese mice were investigated.
      METHODS: High fat diet was used to induce obesity and type 2 diabetes symptoms in
      C57BL6/J mice. To induce SAT expansion through hyperplasia, acellular adipogenic
      cocktails were injected around the SAT depots in high fat diet-induced obese
      mice. RESULTS: Ten weeks after injections, significant neoadipogenesis was
      induced, which not only obviously expanded the volume of SATs but also
      significantly increased the adipocyte density within the whole SAT depots.
      Importantly, these mice exhibited improved glucose tolerance and insulin
      sensitivity (homeostatic model assessment) when compared to control group.
      Further studies suggested that these beneficial metabolic effects were associated
      with elevation of serum high-molecular-weight adiponectin level and reduction of
      ectopic lipid accumulation in liver. CONCLUSIONS: These findings not only further
      supported the protective role of SAT in the pathogenesis of type 2 diabetes but
      also highlighted the importance of adipocyte hyperplasia in this protective
      effect.

PMID- 24435988
TI  - [Microanalytical identification of barium sulphate crystals in statoliths of
      Chara rhizoids (Ch. fragilis, desv.)].
AB  - In contrast to the statocytes of higher plants, in which amyloplasts function as
      statoliths, Chara-rhizoids contain statolith vacuoles filled with biocrystallites
      of BaSO4. This was revealed by qualitative and quantitative electron microprobe
      analysis, atomic absorption spectrophotometry and selected area electron
      diffraction. The barium sulphate crystallites are rods which are linearly
      composed of globular subunits approximately 7 nm in diameter.The electron optical
      evidence of the crystallites depends on the nature of the fixatives. Best
      structural preservation was observed after fixation in a buffered solution of
      glutaraldehyde plus acrolein without addition of heavy metals. OsO4 and
      particularly KMnO4 partially dissolve the biocrystallites as well as synthetic
      BaSO4. The crystal solubility must be taken into consideration when micrographs
      of such small crystallites are interpreted.The fact that BaSO4 is chemically very
      inert seems to exclude biochemical interactions of the statoliths with other cell
      components during graviperception. It favours the theory that only the mass of
      the statoliths is effective. 

PMID- 24435987
TI  - Improved protein quality in transgenic soybean expressing a de novo synthetic
      protein, MB-16.
AB  - To improve soybean [Glycine max (L.) Merrill] seed nutritional quality, a
      synthetic gene, MB-16 was introduced into the soybean genome to boost seed
      methionine content. MB-16, an 11 kDa de novo protein enriched in the essential
      amino acids (EAAs) methionine, threonine, lysine and leucine, was originally
      developed for expression in rumen bacteria. For efficient seed expression,
      constructs were designed using the soybean codon bias, with and without the KDEL
      ER retention sequence, and beta-conglycinin or cruciferin seed specific protein
      storage promoters. Homozygous lines, with single locus integrations, were
      identified for several transgenic events. Transgene transmission and MB-16
      protein expression were confirmed to the T5 and T7 generations, respectively.
      Quantitative RT-PCR analysis of developing seed showed that the transcript peaked
      in growing seed, 5-6 mm long, remained at this peak level to the full-sized green
      seed and then was significantly reduced in maturing yellow seed. Transformed
      events carrying constructs with the rumen bacteria codon preference showed the
      same transcription pattern as those with the soybean codon preference, but the
      transcript levels were lower at each developmental stage. MB-16 protein levels,
      as determined by immunoblots, were highest in full-sized green seed but the
      protein virtually disappeared in mature seed. However, amino acid analysis of
      mature seed, in the best transgenic line, showed a significant increase of 16.2
      and 65.9 % in methionine and cysteine, respectively, as compared to the parent.
      This indicates that MB-16 elevated the sulfur amino acids, improved the EAA seed
      profile and confirms that a de novo synthetic gene can enhance the nutritional
      quality of soybean. 

PMID- 24435989
TI  - Some effects of analogues of uracil on cell elongation and wall metabolism in
      excised pea root segments.
AB  - Excised root segments of Pisum sativum (L.) cut from the region 2-4 mm behind the
      root tip were cultured in a 2% sucrose medium containing analogues of uracil and
      proline. Of several uracil analogues tested only those containing a thiol group
      (2-thiouracil and 2-thio-6-azauracil) markedly stimulated the growth rate and
      prolonged the duration of growth of the segments, whereas other uracil analogues
      which enhanced growth affected only its duration. Uracil had no effect on cell
      elongation and did not completely prevent the effects of 2-thiouracil and 2-thio
      6-azauracil; it did, however, prevent the stimulation by those analogues without
      a thiol group. Two analogues of proline, thioproline and hydroxyproline, also
      enhanced cell elongation but whereas the effect of hydroxyproline was completely
      prevented by proline, the stimulation produced by thioproline was not.During cell
      elongation, [(14)C]thiouracil was incorporated into RNA, where it replaced
      uracil, and into a non-nucleotide fraction of the cell wall from which it could
      not be removed with perchloric acid, sodium hydroxide, ribonuclease or pronase.
      Experiments using labelled thiouracil, orotic acid, leucine, proline and
      hydroxyproline strongly suggest that 2-thiouracil stimulates the growth rate of
      segments by becoming attached to cysteine in cell-wall proteins and delaying an
      increase in wall rigidity caused by the formation of disulphide bridges between
      proteins. 

PMID- 24435990
TI  - Control of ion absorption by phytochrome.
AB  - Phosphate absorption by segments excised from hypocotyls of Phaseolus aureus
      Roxb. was inhibited by either continuous or short-term illumination with red
      light. Maximal inhibition was observed at pH 6.5. Illumination with 800 erg cm(
      2) s(-1) of red light for 5 min was sufficient to obtain maximal inhibition. The
      effect of red light was completely counteracted by illumination.with 4500 erg cm(
      2) s(-1) of far red light for 3 min, indicating that the effect was mediatedy by
      phytochrome. The efflux of phosphate from the segments was not altered by
      illumination. Similar effects of red and far-red light on potassium influx and
      efflux were also found. 

PMID- 24435991
TI  - The metabolism of indoleacetic acid by barley grains.
AB  - It has been shown that indoleacetic acid (IAA) does not occur in developing
      grains of Hordeum vulgare L. (barley), but that an unidentified indolic compound
      does. This compound, designated 'A', was also found to be a product of the
      metabolism of exogenous IAA by barley. The expression of the gibberellic acid
      effect was delayed for at least 8 h if grains were imbibed in a solution of IAA,
      and during this time, the IAA was metabolised. The enzyme system involved could
      be peroxidase, which was active in the grains at all stages of their development
      and at maturity, and partially purified extracts of peroxidase were found to have
      considerable IAA oxidase activity. 

PMID- 24435992
TI  - The influence of continuous far-red and white light on prenyl chain synthesis in
      plastids of Raphanus seedlings.
AB  - The rate of prenyl chain accumulation (C40 carotenoids; C45 in plastoquinone-9;
      C20 phytyl in chlorophylls, alpha-tocopherol and vitamin K1) in plastids of
      etiolated radish seedlings (Raphanus sativus L.) is determined in continuous
      darkness and after far-red and white light treatment. Continuous far-red light
      (active phytochrome P fr ) stimulates the synthesis of all prenyl chains, but has
      no or only little effect on the dark pattern of the prenyl chain formation. White
      light enhances the accumulation of prenyl chains to a much higher degree than
      does far-red light. By a particularly strong promotion of the accumulation of
      phytyl chains, which are incorporated into chlorophyll, white light changes the
      percentage composition of prenyl chains to that of chloroplasts. 

PMID- 24435993
TI  - Localisation of peroxidase isoenzymes in protoplasts and cell walls of Nicotiana
      tabacum L.
AB  - Upon disk-electrophoresis with guaiacol as a substrate the peroxidase-isoenzymes
      of Nicotiana tabacum (L.) were localized on the gels in two anodic and two
      cathodic groups. By preparation of protoplasts and isolation of cell walls it was
      possible to show that only cathodic enzymes are located in the protoplasts in
      measurable amounts, whereas all the isoenzymes, anodic and cathodic, can be found
      associated with cell walls. The different groups of isoenzymes are bound to the
      cell wall in different ways as evidenced by differences in their extration. It
      seems possible that different biological functions are associated with the
      different groups of isoenzymes.The isoenzyme patterns of different organs and
      tissues of tobacco show qualitative differences only in the anodic (i.e. wall
      located) isoenzymes. It is suggested that the ontogenetic change in peroxidase
      patterns is direct evidence of biochemical differences in the cell walls of the
      different tissues and organs. 

PMID- 24435994
TI  - Staining of sieve tube mitochondria in coleoptiles of rice (Oryza sativa L.) with
      diaminobenzidine.
AB  - Diaminobenzidine has been used to locate sites of oxidizing cytochromes in rice
      coleoptiles. The mitochondria of mature sieve tubes show a positive reaction
      which to visual inspection appears as strong as the reaction of companion cell
      mitochondria. 

PMID- 24435995
TI  - [The role of inorganic phosphate in the regulation of the phosphoenolpyruvate
      carboxylase of Mesembryanthemum crystallinum L].
AB  - The activity of the phosphoenolpyruvate (PEP) carboxylase isolated from non
      saline grown plants of the salt-tolerant plant Mesembryanthemum crystallinum is
      strongly inhibited by malate. This inhibition was found to depend on the pH
      (rising with increasing H(+)-concentrations) and on the concentration of malate
      used. The addition of inorganic phosphate (appropriate concentration 30 mM) to
      the in-vitro enzyme assay prior to malate addition results in a remarkable
      compensation of malate-caused inhibition of the enzyme activity. Again a
      dependency upon the pH can be observed. The ability of inorganic phosphate to
      restore malate-caused inhibition of the PEP-carboxylase increases with increasing
      pH.Another potent inhibitor of the PEP-carboxylase is NaCl, which shows a minimum
      inhibition at pH 7. At this pH a concentration of more than 60 mM NaCl is needed
      to reduce the activity of the enzyme below the control level with a 50%
      inhibition is reached at 150 mM. If the addition of NaCl is performed in the
      presence of 30 mM inorganic phosphate the inhibition is less pronounced. The
      enzyme now tolerates about 100 mM higher concentrations of NaCl without being
      inhibited.NaCl-treatment of Mesembryanthemum crystallinum plants results in an
      increase of inorganic phosphate in the cells with a concomitant establishment of
      a Crassulacean acid metabolism. The present results support evidence for a
      protective function of inorganic phosphate (compensation of NaCl-induced enzyme
      inhibition), possibly a commen reaction involved in the question of salt
      tolerance, and a more specific function (restriction of malatecaused inhibition
      of the PEP-carboxylase) providing the enzymatic background for the malate
      accumulation in Mesembryanthemum crystallinum. 

PMID- 24435996
TI  - Light-dependent synthesis of glutamine in pea-chloroplast preparations.
AB  - Isolated-chloroplast preparations obtained from Pisum sativum (L.) plants
      synthesized L-[(14)C]glutamine from L-[(14)C]glutamate in the light. In the dark
      appreciable synthesis of glutamine occurred only in the presence of added ATP.
      Photoconversion of glutamate to glutamine was inhibited by millimolar
      concentrations of ammonium or nitrite, and by DCMU. The inhibition due to DCMU,
      NO2 (-), or NH4 (+) was markedly relieved by ATP. ATP-dependent synthesis of
      glutamine in the dark was not inhibited by ammonium or nitrite ions.The data
      suggest that ATP necessary to support chloroplastic glutamine synthesis may be
      derived from noncyclic or pseudocyclic phosphorylation. Since high ammonia
      concentrations appear to inhibit chloroplastic glutamine synthesis by uncoupling
      photophosphorylation, it is possible that ATP synthesized outside the chloroplast
      may be required to drive the rapid synthesis of glutamine that occurs in leaves
      subjected to toxic levels of ammonia. 

PMID- 24435997
TI  - Light-regulation of enzyme activity in anacystis nidulans (Richt.).
AB  - The effect of light on the levels of activity of six enzymes which are light
      modulated in higher plants was examined in the photosynthetic procaryot Anacystis
      nidulans. Ribulose-5-phosphate kinase (EC 2.7.1.19) was found to be light
      activated in vivo and dithiothreitol-activated in vitro while glucose-6-phosphate
      dehydrogenase (EC 1.1.1.49) was light-inactivated and dithiothreitol-inactivated.
      The enzymes fructose-1,6-diphosphate phosphatase (EC 3.1.3.11), sedoheptulose-1,7
      diphosphate phosphatase, NAD- and NADP-linked glyceraldehyde-3-phosphate
      dehydrogenase (EC 1.2.1.12; EC 1.2.1.13) were not affected by light treatment of
      the intact algae, but sedoheptulose-diphosphate phosphatase and the
      glyceraldehyde-3-phosphate dehydrogenases were dithiothreitol-activated in crude
      extracts. Light apparently controls the activity of the reductive and oxidative
      pentose phosphate pathway in this photosynthetic procaryot as in higher plants,
      through a process which probably involves reductive modulation of enzyme
      activity. 

PMID- 24435998
TI  - Abscisic acid as a root growth inhibitor: Physiological analyses.
AB  - Abscisic acid (ABA) moves basipetally and laterally in maize (Zea mays L.) root
      segments placed horizontally; its transport properties are thus similar to those
      of the growth-inhibiting substances produced by the root cap. The two opposite
      flows af ABA and of indolyl-3-acetic acid (IAA) - substances both present in the
      cap - may control elongation and georeaction of the root. 

PMID- 24435999
TI  - [Poly- and metaphosphates in higher plants (Lemnaceae)].
AB  - After pulse-labelling with [(32)P]orthophosphate of higher plants (Lemna
      perpusilla (Torrey) and Lemna gibba (L.)) which were previously grown in a P-free
      medium for 24 h, the [(32)P]-radioactivity is partially incorporated into
      condensed inorganic phosphates. The isolation of the latter was achieved by joint
      extraction with the nucleic acids and fractionation on methylated serum albumin
      and Kieselgur (MAK). Two-dimensional thin layer chromatography on a mixture of
      cellulose and microcrystalline cellulose revealed that (32)P-radioactivity was
      present in linear oligophosphates with 2 to 7 residues as well as in cyclic tri-,
      tetra-, penta- and hexametaphosphates. Among the low-molecular condensed
      inorganic phosphates the trimetaphosphate contained significantly more
      radioactivity than the other compounds. It is supposeded that the condensed
      phosphates are involved in the regulation of the ATP-ADP-Pi-system. 

PMID- 24436000
TI  - The effect of vomifoliol on stomatal aperture.
AB  - Vomifoliol, a compound related to abscisic acid (ABA) but lacking the 2,4
      pentadiene sidechain and so far found in four different plant families, caused as
      much stomatal closure in epidermal strips of Eichhornia crassipes (Mart.) Solms
      as ABA at identical concentrations. It appears worthwhile to investigate whether
      vomifoliol plays a role as an endogenous regulator of stomatal aperture. 

PMID- 24436001
TI  - The role of stelar auxin in the development of the primary root of Zea mays.
AB  - Neither the removal of the stele, which contains over 90% of the auxin found in
      the primary roots of Zea mays L., nor its replacement by auxin (indole-3-acetic
      acid, IAA) solutions had any demonstrable effect on the elongation of root tips
      or subapical cortical cylinders (except inhibition at higher IAA concentrations).
      Other possible developmental roles for stelar auxin in roots are discussed. 

PMID- 24436002
TI  - Laterally projecting cerebrospinal fluid-contacting cells in the lamprey spinal
      cord are of two distinct types.
AB  - Cerebrospinal fluid-contacting (CSF-c) cells are found in all vertebrates, but
      their function remains elusive. In the lamprey spinal cord, they surround the
      central canal and some have processes passing the gray matter to the lateral edge
      of the flattened spinal cord. Stimulation of CSF-c cells at the central canal
      elicits GABAergic inhibitory postsynaptic potentials (IPSPs) in intraspinal
      stretch receptor neurons (edge cells). Here, we characterize laterally projecting
      CSF-c cells according to their morphology, phenotype, and neuronal properties by
      using immunohistochemistry, retrograde tracing, calcium imaging, and whole-cell
      recordings. We identify two types of CSF-c cells. Type 1 cells have a bulb-like
      ending that protrudes into the central canal and a lateral process that ramifies
      ventrolaterally and laterally with a dense plexus surrounding the
      mechanosensitive dendrites of the edge cells. Most type 1 cells fire spontaneous
      action potentials that are abolished by tetrodotoxin, and all display spontaneous
      excitatory postsynaptic potentials and IPSPs that remain in the presence of
      tetrodotoxin. GABA and somatostatin are colocalized in type 1 cells, and they
      express both GABA and glutamate receptors. Type 2 cells, on the other hand, have
      a flat ending protruding into the central canal and a laterally projecting
      process that ramifies only at the lateral edge. These cells show immunoreactivity
      to taurine, but they do not express GABA or somatostatin, nor do they have any
      active neuronal properties. Type 2 cells might be a form of glia. Type 1 CSF-c
      cells are neurons and may play a modulatory role by influencing edge cells and
      thus the locomotor-related sensory feedback.

PMID- 24436003
TI  - Cooperative and diminutive effects of pnicogen bonds and cation-pi interactions.
AB  - The interplay between pnicogen bonds and cation-pi interactions has been
      investigated at the MP2/aug-cc-pVDZ level. Interesting cooperative and diminutive
      effects are observed when pnicogen bonds and cation-pi interactions coexist in
      the same complex. These effects have been analyzed in terms of the structural,
      energetic, and charge-transfer properties of the complexes. The variations in
      electron density at critical points of the intermolecular bond have been used to
      analyze bond strengthening or weakening. The nature of the interactions and the
      mechanisms of cooperative and diminutive effects have been studied by means of
      symmetry-adapted perturbation theory and molecular electrostatic potentials. 

PMID- 24436004
TI  - Developmental toxicity of treated municipal wastewater effluent on Bombina
      orientalis (Amphibia: Anura) embryos.
AB  - Amphibian populations have been decreasing in urban freshwater systems in Korea.
      To elucidate the biological safety of treated wastewater effluent (TWE) in the
      Tancheon basin, the capital area of Korea, a 7-d-exposure Bombina orientalis
      embryo developmental toxicity assay was examined during the breeding season. In
      March, there were no significant differences in embryonic survival or
      malformation among the water samples. In July, following monsoon precipitation,
      embryonic lethality in TWE was significantly higher than in the upstream water
      sample. Malformation in TWE and TWE-mixed waters was significantly higher than in
      the control and upstream water samples. Tail muscle height of tadpoles also
      significantly decreased in TWE and TWE-mixed waters. Heavy metals were not
      detected in any samples. Total nitrogen, total phosphorous, and chemical oxygen
      demand in TWE markedly increased together with a decrease in dissolved oxygen in
      July. The increase in organic and inorganic loading following precipitation could
      have made TWE and TWE-mixed water not suitable for embryonic development. Though
      being managed based on physicochemical criteria, the water quality of TWE may not
      be sufficient to assure normal development of amphibian embryos. An amphibian
      developmental toxicity assay would be helpful for the water-quality management of
      TWE and urban freshwater systems in Korea.

PMID- 24436005
TI  - Routine vitamin A supplementation for the prevention of blindness due to measles
      infection in children.
AB  - BACKGROUND: Reduced vitamin A concentration increases the risk of blindness in
      children infected with the measles virus. Promoting vitamin A supplementation in
      children with measles contributes to the control of blindness in children, which
      is a high priority within the World Health Organization (WHO) VISION 2020 The
      Right to Sight Program. OBJECTIVES: To assess the efficacy of vitamin A in
      preventing blindness in children with measles without prior clinical features of
      vitamin A deficiency. SEARCH METHODS: We searched CENTRAL 2013, Issue 2, MEDLINE
      (1950 to November week 2, 2013), EMBASE (1974 to November 2013) and LILACS (1985
      to November 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs)
      assessing the efficacy of vitamin A in preventing blindness in well-nourished
      children diagnosed with measles but with no prior clinical features of vitamin A
      deficiency. DATA COLLECTION AND ANALYSIS: For the original review, two review
      authors independently assessed studies for eligibility and extracted data on
      reported outcomes. We contacted trial authors of the included studies for
      additional information on unpublished data. We included two RCTs which were
      clinically heterogenous. We presented the continuous outcomes reported as the
      mean difference (MD) with 95% confidence interval (CI). Due to marked clinical
      heterogeneity we considered it inappropriate to perform a meta-analysis. MAIN
      RESULTS: For the first publication of this review, two RCTs involving 260
      children with measles which compared vitamin A with placebo met the inclusion
      criteria. Neither study reported blindness or other ocular morbidities as end
      points. One trial of moderate quality suggested evidence of a significant
      increase in serum retinol levels in the vitamin A group one week after two doses
      of vitamin A (MD 9.45 uG/dL, 95% CI 2.19 to 16.71; 17 participants) but not six
      weeks after three doses of vitamin A (MD 2.56 uG/dL, 95% CI -5.28 to 10.40; 39
      participants). There was no significant difference in weight gain six weeks (MD
      0.39 kg, -0.04 to 0.82; 48 participants) and six months (MD 0.52 kg, 95% CI -0.08
      to 1.12; 36 participants) after three doses of vitamin A. The second trial found
      no significant difference in serum retinol levels two weeks after a single dose
      of vitamin A (MD 2.67 uG/dL, 95% CI -0.29 to 5.63; 155 participants). No adverse
      event was reported in either study. We did not find any new randomised controlled
      trials for this update. AUTHORS' CONCLUSIONS: We did not find any trials
      assessing whether or not vitamin A supplementation in children with measles
      prevents blindness, as neither study reported blindness or other ocular
      morbidities as end points. However, vitamin A use in children should be
      encouraged for its proven clinical benefits.

PMID- 24436006
TI  - Banding artifact removal for bSSFP imaging with an elliptical signal model.
AB  - PURPOSE: Balanced steady-state free precession (bSSFP) imaging has broad clinical
      applications by virtue of its high time efficiency and desirable contrast.
      Unfortunately, banding artifact is often seen as a result of signal modulation
      due to B0 inhomogeneity. This study aims to develop an effective method for
      banding artifact suppression. METHODS: bSSFP is analyzed with an elliptical
      signal model. A simple analytical "Geometric-Solution" (GS) is presented to
      demodulate the signal from B0 inhomogeneity dependence with phase-cycled bSSFP
      data from both a computer simulation and experiments using phantom and human
      subjects. RESULTS: The proposed algorithm is able to remove banding artifacts
      completely. It also compares favorably with the complex sum (CS), which is
      considered one of the more efficient methods for banding artifact correction.
      CONCLUSION: Using an elliptical signal model, an analytical solution to the bSSFP
      banding problem has been found and demonstrated with simulation as well as
      phantom and in vivo experiments.

PMID- 24436007
TI  - Precise, fast, and flexible determination of protein interactions by affinity
      capillary electrophoresis: part 3: anions.
AB  - The binding of physiologically anionic species or negatively charged drug
      molecules to proteins is of great importance in biochemistry and medicine. Since
      affinity capillary electrophoresis (ACE) has already proven to be a suitable
      analytical tool to study the influence of ions on proteins, this technique was
      applied here for comprehensively studying the influence of various anions on
      proteins of BSA, beta-lactoglobulin, ovalbumin, myoglobin, and lysozyme. The
      analysis was performed using different selected anions of succinate, glutamate,
      phosphate, acetate, nitrate, iodide, thiocyanate, and pharmaceuticals (salicylic
      acid, aspirin, and ibuprofen) that exist in the anionic form at physiological pH
      7.4. Due to the excellent repeatability and precision of the ACE measurements,
      not necessarily strong but significant influences of the anions on the proteins
      were found in many cases. Different influences in the observed bindings indicated
      change of charge, mass, or conformational changes of the proteins due to the
      binding with the studied anions. Combining the mobility-shift and pre-equilibrium
      ACE modes, rapidity and reversibility of the protein-anion bindings were
      discussed. Further, circular dichroism has been used as an orthogonal approach to
      characterize the interactions between the studied proteins and anions to confirm
      the ACE results. Since phosphate and various anions from amino acids and small
      organic acids such as succinate or acetate are present in very high
      concentrations in the cellular environment, even weak influences are certainly
      relevant as well. 

PMID- 24436008
TI  - Expression of metalloproteinases 2 and 9 and tissue inhibitors 1 and 2 as
      predictors of lymph node metastases in oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: The matrix metalloproteinases (MMPs) and their tissue inhibitor of
      metalloproteinases (TIMPs) can decompose extracellular matrix (ECM) components
      and brake down basement membranes and, thus, promote tumor local invasion and
      metastasis. METHODS: We studied 41 patients with squamous cell carcinoma (SCC) of
      the oropharynx who underwent surgical treatment. Material was diagnosed by
      routine procedure and examined by immunohistochemical analysis and dot blot
      technique. We searched for correlations between expressions of MMPs, such as MMP
      2 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 and treatment outcome.
      RESULTS: We found cytoplasmic expression of analyzed proteins, both in cancer
      cells and tumor stroma. The expression of analyzed antigens was higher in
      patients with lymph node metastases comparing patients without lymph node
      involvement. CONCLUSION: Our data suggest that microenvironment changes are one
      of key factors in tumor progression. Divergent expression of MMPs and their
      inhibitors might be used as prognostic factor of oropharyngeal carcinoma
      progression.

PMID- 24436010
TI  - The influence of chemical composition of commercial lemon essential oils on the
      growth of Candida strains.
AB  - Candida yeasts are saprophytes naturally present in the environment and forming
      colonies on human mucous membranes and skin. They are opportunistic fungi that
      cause severe and even fatal infections in immunocompromised individuals. Several
      essential oils, including eucalyptus, pine, cinnamon and lemon, have been shown
      to be effective against Candida strains. This study addresses the chemical
      composition of some commercial lemon essential oils and their antifungal
      potential against selected Candida yeast strains. Antifungal potential and
      minimum inhibitory concentrations were determined for six commercial lemon
      essential oils against five Candida yeast strains (Candida albicans 31, Candida
      tropicalis 32, Candida glabrata 33, Candida glabrata 35 and Candida glabrata 38).
      On the basis of the GCMS analysis, it was found that the tested lemon essential
      oils had different chemical compositions, but mostly, they contained almost
      exclusively terpenes and oxygenated terpenes. The tests show that antifungal
      potential of lemon essential oils against Candida yeast strains was related to
      the high content of monoterpenoids and the type of Candida strains. From six
      tested commercial oils, only four (ETJA, Vera-Nord, Avicenna-Oil and Aromatic
      Art) shows antifungal potential against three Candida species (C. albicans, C.
      tropicalis and C. glabrata). Vera-Nord and Avicenna-Oil show the best activity
      and effectively inhibit the growth of the C. albicans strain across the full
      range of the concentrations used. Our study characterises lemon essential oils,
      which could be used as very effective natural remedies against candidiasis caused
      by C. albicans. 

PMID- 24436009
TI  - Evidence for working memory storage operations in perceptual cortex.
AB  - Isolating the short-term storage component of working memory (WM) from the myriad
      of associated executive processes has been an enduring challenge. Recent efforts
      have identified patterns of activity in visual regions that contain information
      about items being held in WM. However, it remains unclear (1) whether these
      representations withstand intervening sensory input and (2) how communication
      between multimodal association cortex and the unimodal perceptual regions
      supporting WM representations is involved in WM storage. We present evidence that
      the features of a face held in WM are stored within face-processing regions, that
      these representations persist across subsequent sensory input, and that
      information about the match between sensory input and a memory representation is
      relayed forward from perceptual to prefrontal regions. Participants were
      presented with a series of probe faces and indicated whether each probe matched a
      target face held in WM. We parametrically varied the feature similarity between
      the probe and target faces. Activity within face-processing regions scaled
      linearly with the degree of feature similarity between the probe face and the
      features of the target face, suggesting that the features of the target face were
      stored in these regions. Furthermore, directed connectivity measures revealed
      that the direction of information flow that was optimal for performance was from
      sensory regions that stored the features of the target face to dorsal prefrontal
      regions, supporting the notion that sensory input is compared to representations
      stored within perceptual regions and is subsequently relayed forward. Together,
      these findings indicate that WM storage operations are carried out within
      perceptual cortex. 

PMID- 24436011
TI  - Detection of antibodies against Paracoccidioides brasiliensis in free-range
      domestic pigs (Sus scrofa).
AB  - Paracoccidioidomycosis, caused by the thermodimorphic fungus Paracoccidioides
      brasiliensis, is a human systemic mycosis prevalent in Latin America.
      Paracoccidioidomycosis affects mainly male rural workers, causing granulomatous
      lesions in several organs such as the lungs, liver and spleen. The participation
      of other animal species in the fungus epidemiology is not well understood. The
      objective of this study was to evaluate the infection of free-range domestic pigs
      by P. brasiliensis. Serum samples from 106 pigs were analyzed by ELISA and the
      immunodiffusion test, using P. brasiliensis gp43 and exoantigen as antigens,
      respectively. The overall positivity to gp43 in ELISA was 37.7 %, although no
      reactivity was observed in the immunodiffusion test and nor was P. brasiliensis
      detected in tissue samples (spleen, lung, liver and lymph nodes) from slaughtered
      animals submitted to culture, histopathological examination and PCR analysis.
      Five pigs seronegative to gp43 were exposed to natural infection by P.
      brasiliensis, and all animals seroconverted 3 months after exposure. The results
      suggest that free-range pigs are frequently infected with P. brasiliensis but are
      resistant to disease development. This is the first report of
      paracoccidioidomycosis in pigs.

PMID- 24436012
TI  - Candida albicans and Candida parapsilosis rapidly up-regulate galectin-3
      secretion by human gingival epithelial cells.
AB  - Galectin-3 is a beta-galactoside-binding C-type lectin that plays an important
      role in innate immunity. The purpose of this study was to determine whether
      Candida albicans and Candida parapsilosis up-regulate galectin-3 secretion by
      human gingival epithelial cells and gingival fibroblasts. Ca9-22, a human
      gingival epithelial cell line, and human gingival fibroblasts were incubated in
      the presence or absence of C. albicans or C. parapsilosis without serum. Levels
      of secreted human galectin-3 in culture supernatants were measured by enzyme
      linked immunosorbent assay. We also pretreated Ca9-22 cells with cytochalasin D
      (an actin polymerization inhibitor), ALLN (a calpain inhibitor) and LY294002 [a
      phosphatidylinositol-3 kinase (PI3K) inhibitor] to determine whether the up
      regulation of galectin-3 secretion was mediated by cytoskeletal changes, protease
      activity, or PI3K signaling. Galectin-3 secretion was significantly and rapidly
      up-regulated by live C. albicans and C. parapsilosis, as well as heat-killed C.
      albicans. In addition, cytochalasin D, LY294002 and ALLN did not inhibit the up
      regulation in galectin-3 secretion. These results suggest that both live and heat
      killed C. albicans and C. parapsilosis may increase the activity of the innate
      immune system and invasion by other microorganisms via up-regulation of galectin
      3 secretion. 

PMID- 24436013
TI  - In vitro effect of amphotericin B on Candida albicans, Candida glabrata and
      Candida parapsilosis biofilm formation.
AB  - Candida spp. biofilm is considered highly resistant to conventional antifungals.
      The aim of this study was to investigate the in vitro effect of amphotericin B on
      Candida spp. biofilms at different stages of maturation. We investigated the
      activity of amphotericin B against 78 clinical isolates of Candida spp.,
      representing three species, growing as planktonic and sessile cells, by a widely
      accepted broth microdilution method. The in vitro effect on sessile cell
      viability was evaluated by MTT reduction assay. All examined strains were
      susceptible to amphotericin B when grown as free-living cells. At the early
      stages of biofilm maturation 96.7-100.0 % strains, depending on species,
      displayed amphotericin B sessile minimal inhibitory concentration (SMIC) <= 1
      MUg/mL. Mature Candida spp. biofilm of 32.1-90.0 % strains displayed amphotericin
      B SMIC <= 1 MUg/mL. Based on these results, amphotericin B displays species- and
      strain-depending activity against Candida spp. biofilms.

PMID- 24436014
TI  - The usefulness of DNA sequencing after extraction by Whatman FTA filter matrix
      technology and phenotypic tests for differentiation of Candida albicans and
      Candida dubliniensis.
AB  - Since C. dubliniensis is similar to C. albicans phenotypically, it can be
      misidentified as C. albicans. We aimed to investigate the prevalence of C.
      dubliniensis among isolates previously identified as C. albicans in our stocks
      and to compare the phenotypic methods and DNA sequencing of D1/D2 region on the
      ribosomal large subunit (rLSU) gene. A total of 850 isolates included in this
      study. Phenotypic identification was performed based on germ tube formation,
      chlamydospore production, colony colors on chromogenic agar, inability of growth
      at 45  degrees C and growth on hypertonic Sabouraud dextrose agar. Eighty
      isolates compatible with C. dubliniensis by at least one phenotypic test were
      included in the sequence analysis. Nested PCR amplification of D1/D2 region of
      the rLSU gene was performed after the fungal DNA extraction by Whatman FTA filter
      paper technology. The sequencing analysis of PCR products carried out by an
      automated capillary gel electrophoresis device. The rate of C. dubliniensis was
      2.35 % (n = 20) among isolates previously described as C. albicans. Consequently,
      none of the phenotypic tests provided satisfactory performance alone in our
      study, and molecular methods required special equipment and high cost. Thus, at
      least two phenotypic methods can be used for identification of C. dubliniensis,
      and molecular methods can be used for confirmation.

PMID- 24436015
TI  - A donor-stabilized zwitterionic "half-parent" phosphasilene and its unusual
      reactivity towards small molecules.
AB  - The stabilization of the labile, zwitterionic "half-parent" phosphasilene 4
      L'Si=PH (L'=CH[(C=CH2)CMe(NAr)2]; Ar=2,6-iPr2C6H3) could now be accomplished by
      coordination with two different donor ligands (4-dimethylaminopyridine (DMAP) and
      1,3,4,5-tetramethylimidazol-2-ylidene), affording the adducts 8 and 9,
      respectively. The DMAP-stabilized zwitterionic "half-parent" phosphasilene 8 is
      capable of transferring the elusive parent phosphinidene moiety (:PH) to an
      unsaturated organic substrate, in analogy to the "free" phosphasilene 4.
      Furthermore, compounds 4 and 8 show an unusual reactivity of the Si=P moiety
      towards small molecules. They are capable of adding dimethylzinc and of
      activating the S-H bonds in H2S and the N-H bonds in ammonia and several
      organoamines. Interestingly, the DMAP donor ligand of 8 has the propensity to act
      as a leaving group at the phosphasilene during the reaction. Accordingly,
      treatment of 8 with H2S affords, under liberation of DMAP, the unprecedented
      thiosilanoic phosphane LSi=S(PH2) 16 (L=HC(CMe[2,6-iPr2C6H3N])2). Compounds 4 and
      8 react with ammonia both affording L'Si(NH2)PH2 17, respectively. In addition,
      the reaction of 8 with isoproylamine, p-toluidine, and pentafluorophenylhydrazine
      lead to the corresponding phosphanylsilanes L'Si(PH2)NHR (R=iPr 18 a; R=C6H5-CH3
      18 b, R=NH(C6F5) 18 c), respectively.

PMID- 24436016
TI  - HPV16 E6*II gene expression in intraepithelial cervical lesions as an indicator
      of neoplastic grade: a pilot study.
AB  - Integration of the HPV genome into a host cell DNA leads to the deregulated
      overexpression of the viral E6 and E7 oncoproteins, and this is a key factor for
      progression from low-grade cervical lesions to high-grade lesions and invasive
      cervical cancer. The aim of our study was to analyze the expression levels of HPV
      E6*I/E6*II and E7 genes in cervical neoplasia of different grades. The analysis
      involved 10 low-grade squamous intraepithelial lesions (CIN1), 15 high-grade
      lesions (CIN2 and CIN3), as well as normal cytology samples (n=10). HPV
      genotyping was done using RealLine HPV 16/18 kit. The expression analysis was
      performed in real-time PCR assay using gene-specific primers and SYBR Green.
      HPV16 DNA was found in 65.71% patients, including also normal cytology samples.
      The increased expression level of E6*I was observed in 12 (34.3%) patients. The
      expression of E6*II was increased in 10 (28.6%) samples, and E7 overexpression
      was found in 14 (40%) patients. Significant positive correlation was observed
      between the amount of HPV16 DNA and the levels of E6*I and E6*II expression.
      There were no statistically significant differences in expression levels of the
      studied genes between the groups (CIN1 vs. CIN2/CIN3 vs. normal cytology).
      Statistically significant differences were found in CIN2/CIN3 group, with the
      higher expression of E6*II as compared with E6*I. We suggest that the expression
      level of E6*II gene might be used as an indicator of cervical cancer severity, in
      patients with high-grade cervical neoplasia, but these observations need to be
      confirmed in a larger patient cohort.

PMID- 24436017
TI  - Calories, carbohydrates, and cancer therapy with radiation: exploiting the five
      R's through dietary manipulation.
AB  - Aggressive tumors typically demonstrate a high glycolytic rate, which results in
      resistance to radiation therapy and cancer progression via several molecular and
      physiologic mechanisms. Intriguingly, many of these mechanisms utilize the same
      molecular pathways that are altered through calorie and/or carbohydrate
      restriction. Furthermore, poorer prognosis in cancer patients who display a
      glycolytic phenotype characterized by metabolic alterations, such as obesity and
      diabetes, is now well established, providing another link between metabolic
      pathways and cancer progression. We review the possible roles for calorie
      restriction (CR) and very low carbohydrate ketogenic diets (KDs) in modulating
      the five R's of radiotherapy to improve the therapeutic window between tumor
      control and normal tissue complication probability. Important mechanisms we
      discuss include (1) improved DNA repair in normal, but not tumor cells; (2)
      inhibition of tumor cell repopulation through modulation of the PI3K-Akt-mTORC1
      pathway downstream of insulin and IGF1; (3) redistribution of normal cells into
      more radioresistant phases of the cell cycle; (4) normalization of the tumor
      vasculature by targeting hypoxia-inducible factor-1alpha downstream of the PI3K
      Akt-mTOR pathway; (5) increasing the intrinsic radioresistance of normal cells
      through ketone bodies but decreasing that of tumor cells by targeting glycolysis.
      These mechanisms are discussed in the framework of animal and human studies,
      taking into account the commonalities and differences between CR and KDs. We
      conclude that CR and KDs may act synergistically with radiation therapy for the
      treatment of cancer patients and provide some guidelines for implementing these
      dietary interventions into clinical practice.

PMID- 24436018
TI  - N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver
      steatosis and inflammation in relation to PPAR-alpha upregulation and NF-kappaB
      DNA binding abrogation.
AB  - SCOPE: Dietary n-3 long-chain PUFAs (n-3 LCPUFAs) supplementation was studied in
      an HFD-induced (HFD is high-fat diet) steatosis and inflammation in relation to
      peroxisome proliferator-activated receptor alpha (PPAR-alpha) and nuclear factor
      kappaB (NF-kappaB) signaling. METHODS AND RESULTS: Male C57BL/6J mice received
      (i) control diet (10% fat, 20% protein, 70% carbohydrate), (ii) control diet plus
      n-3 LCPUFAs (daily doses of 108 mg/kg body weight of eicosapentaenoic acid plus
      92 mg/kg body weight of docosahexaenoic acid), (iii) HFD (60% fat, 20% protein,
      20% carbohydrate), or (iv) HFD plus n-3 LCPUFAs for 12 wk. PPAR-alpha, tumor
      necrosis factor alpha (TNF-alpha), and IL-1beta mRNA expression, acyl-CoA oxidase
      1 (ACOX1), and carnitine-acyl-CoA transferase 1 (CAT-I) protein contents, and NF
      kappaB DNA binding activity were measured. HFD significantly decreased liver PPAR
      alpha, ACOX1, and CAT-I levels with NF-kappaB activation, higher TNF-alpha and IL
      1beta expression, and steatosis development. These changes were either reduced or
      normalized to control values in animals subjected to HFD plus n-3 LCPUFAs, with
      establishment of an inverse association between NF-kappaB activation and PPAR
      alpha mRNA expression (r = -0.66, p < 0.0001). CONCLUSION: Data presented
      indicate that n-3 LCPUFAs supplementation prevents liver steatosis and
      inflammation induced by HFD, with underlying mechanisms involving enhanced PPAR
      alpha signaling and diminished NF-kappaB activation.

PMID- 24436020
TI  - The lysosome-concept in plants : I. Peroxidases associated with subcellular and
      wall fractions of maize root tips: Implications for vacuole development.
AB  - Only 11% of the total peroxidase activity in a root tip homogenate of Zea mays
      (L.) was sedimentable. The majority of sedimentable activity was bound to
      membrane fractions with which acid hydrolases were also associated.Peroxidase
      activity was released from a cell wall fraction exhaustively washed using
      homogenization and detergent. The specific activities of the washings were 3-10
      fold higher than in the sedimentable and soluble fractions. A quarter of the wall
      associated activity was only released after treatment of the washed wall
      preparation with cellulase.Histochemistry shows peroxidase associated with cell
      walls. The only activity within the cell was observed associated with the inner
      surface of the provacuole membranes. The provacuoles were observed fusing in
      maturing cells. No peroxidase was seen in the Golgi.One peroxidase isozyme was
      apparently specifically associated with the sedimentable membrane fractions and
      may represent the activity observed in the provacuole membranes. Three fast
      migrating isozymes were restricted to the soluble fractions while at least three
      slow migrating isozymes were wall associated. One of the latter was specifically
      released from the wall by calcium nitrate. The relationship between the isozymes
      is discussed.A scheme for the origin of vacuoles is proposed. 

PMID- 24436019
TI  - Body fat, body fat distribution, lean body mass and atrial fibrillation and
      flutter. A Danish cohort study.
AB  - OBJECTIVE: It is recognized that higher height and weight are associated with
      higher risk of atrial fibrillation or flutter (AF) but it is unclear whether risk
      of AF is related to body fat, body fat location, or lean body mass. METHODS: This
      article reports the Danish population-based prospective cohort Diet, Cancer and
      Health study conducted among 55,273 men and women 50-64 years of age at
      recruitment. The associations between bioelectrical impedance derived measures of
      body composition and combinations of anthropometric measures of body fat
      distribution and risk of an incident record of AF in the Danish Registry of
      Patients were investigated. RESULTS: During follow-up (median 13.5 years) AF
      developed in 1,669 men and 912 women. Higher body fat at any measured location
      was associated with higher risk of AF. The adjusted hazard ratio (HR) per 1 sex
      specific standard deviation (SD) increment in body fat mass was 1.29 (95%
      confidence interval [CI], 1.24-1.33). Higher lean body mass was also associated
      with a higher risk of AF. The adjusted HR for 1 sex-specific SD increment was
      1.40 (95% CI, 1.35-1.45). CONCLUSION: Higher body fat and higher lean body mass
      were both associated with higher risk of AF.

PMID- 24436021
TI  - The lysosome-concept in plants : II. Location of acid hydrolases in maize root
      tips.
AB  - The sedimentability of eight acid hydrolases in an homogenate from root tips of
      Zea mays (L.) varied between 13% (alpha-glucosidase) and 46% (beta-N
      acetylglucosaminidase) of the total activity. Between 20% and 30% of total
      activity of the majority of acid hydrolases examined was sedimentable.High
      specific activities of acid hydrolases (up to ten times the sedimentable or
      soluble activities) were associated with the cell walls, and considerable amounts
      of this activity (20-60%, depending on the enzyme) could only be released by
      cellulase treatment.Mitochondria-free membrane fractions isolated from the 8000
      g, 25000 g and microsomal fractions contained acid hydrolase activities. The
      membranes could be separated into two bands on Ficoll gradients, but acid
      hydrolase activities were present in both bands.The 25000 g fraction was
      incubated with glucose-6-phosphate and lead nitrate to label the vesicles
      containing neutral phosphatase with lead phosphate. The labelled vesicles were
      separated from the remaining vesicles by density grandients. The majority of acid
      phosphatase, beta-glucosidase, beta-galactosidase and peroxidase activities were
      associated with the unlabelled fraction. Phosphodiesterase was present in both
      fractions. The peroxidase isozyme thought to be tonoplast-associated (Parish,
      1975) was found in the unlabelled vesicles.It was concluded that sedimentable
      acid hydrolases are associated with a specific class or classes of membrane.More
      than 60% of the sedimentable acid hydrolase activities were strongly bound to
      membranes. A membrane model of lysosome action is proposed.The isozymes of acid
      phosphatase and beta-galactosidase present in the cell wall, sedimentable
      fractions and the supernatant were examined.A number of tentative conclusions are
      drawn concerning "lysosomes" and acid hydrolases in plant cells. 

PMID- 24436022
TI  - Importance of the wall for cell division and in the activity of the cytoplasm in
      cultured tobacco protoplasts.
AB  - When tobacco (Nicotiana tabacum L.) mesophyll protoplasts are cultivated in a
      medium in which osmotic pressure is maintained by using salts instead of sugars
      they divide 2-3 times although they never form a rigid wall which could be
      separated from the cytoplasm by the use of plasmolysis. Only a non-rigid pseudo
      wall is present during division, showing that a rigid wall is not required for
      cell division. Diluting the salt medium with 5 volumes of sugar medium leads to
      the formation of a rigid wall as well as the initiation of sustained divisions.
      It is proposed that the complete wall is the place of synthesis of the
      substance(s) necessary for the division activity of the cytoplasm. 

PMID- 24436023
TI  - Nitrate, nitrite and ammonia assimilation by leaves: Effects of inhibitors.
AB  - The assimilation of H(14)CO3 (-), (15)NO3 (-), (15)NO2 (-) and (15)NH4 (+) by
      barley (Hordeum vulgare L.) leaf segments in the presence of a number of
      metabolic inhibitors was studied in experiments where the substrates and
      inhibitors were vacuum infiltrated into the tissue. 3-(3',4'-Dichlorophenyl)-1,1
      dimethylurea (DCMU), carbonyl-cyanide-m-chlorophenylhydrazone (CCCP), and
      iodoacetate (IOA) inhibited (14)CO2 fixation and (15)NO3 (-) and (15)NO2 (-)
      assimilation in the light. (15)NH4 (+) assimilation in the light was only
      inhibited 70% by 10(-4)M DCMU. (15)NH4 (+) assimilation was stimulated by 10(-5)M
      CCCP but was inhibited by concentrations of CCCP above 5*10(-5)M. In double-label
      experiments (15)NO3 (-) assimilation was less sensitive than (14)CO2 fixation to
      both DCMU and CCCP. CCCP but not DCMU stimulated NO2 (-) accumulation in dark and
      IOA was inhibitory. The rate of NO2 (-) accumulation in the light in the presence
      of DCMU or atrazine was similar to that in the dark and in all cases NO2 (-)
      accumulation was inhibited about 90% by oxygenation of the medium. The results
      indicate that the assimilation of all nitrogen species is closely linked to
      photosynthetic electron transport, that rate of assimilation of nitrogen species
      is independent of rate of assimilation of CO2, and that the dark in-vivo nitrate
      reduction is a useful analogue of the mechanism operating in the light only if
      electron flow to oxygen is impaired. 

PMID- 24436024
TI  - Leaf development and phloem transport in Cucurbita pepo: Carbon economy.
AB  - Net photosynthesis, dark respiration and growth for leaf 5 of Cucurbita pepo L.
      plants grown under controlled conditions were measured and the data used for an
      assessment of the changes in carbon balance during growth of the leaf through
      expansion to maturity. The blade is first capable of net CO2 fixation when ca. 8%
      expanded but the initial rapid growth during this period is sustained almost
      entirely through imported nutrients. When the growth rate starts to decline
      rapidly the net photosynthetic capacity of the blade begins to increase. This
      increase is accompanied by an expansion of the intercellular spaces and by
      decreasing dark respiration measured at night and in dark periods during the day.
      The blade becomes completely independent of phloem imported nutrients and begins
      to export excess photosynthate when the phase of rapid decrease in relative
      growth rate is almost complete at about 45% expansion. Maximum net photosynthesis
      of ca. 11 mg CO2 h(-1) dm(-2) is achieved at 70% expansion. The first detectable
      synthesis of the transport sugars stachyose and raffinose in the blade coincides
      with the beginning of intralaminar phloem transport from the tip to the base of
      the leaf. The synthesis of sucrose, the other major transport sugar, is
      detectable at all stages of leaf development. 

PMID- 24436025
TI  - Developmental studies on microbodies in wheat leaves : III. On the photocontrol
      of microbody development.
AB  - 1. In etiolated wheat (Triticum aestivum L.) leaves, the development of the
      microbody enzymes catalase, hydroxypyruvate reductase, and glycolate oxidase was
      specifically stimulated by short treatments of the seedlings with red light,
      although the increases were less than observed after treatment with continuous
      white light. A comparison of the effects of short red and far-red exposures
      indicated the involvement of phytochrome. 2. Continuous far-red light treatments
      also enhanced the development of microbody enzymes. Catalase activity continued
      to increase at a high rate even after return from a prolonged far-red
      illumination to darkness, while the increase in the activities of glycolate
      oxidase and hydroxypyruvate reductase fell to the dark rates when the tissue was
      removed from the light. However, even at higher intensities of continuous far-red
      light the microbody enzymes reached only considerably lower activities than in
      white light. During continuous irradiation of equal quantum flux, the microbody
      enzymes reached higher activities in red than in far-red light, but the highest
      activities were observed in blue light, which had similar effects as white light.
      The quantitative difference between the effects of prolonged red or blue light
      depended also on the seed material and growing conditions. In the presence of the
      herbicide 3-amino-1,2,4-triazole the increase of glycolate-oxidase activity was
      reduced in red light but was affected much less, if at all, in blue light. 3.
      Continuous irradiations with all three light qualities used (red, far-red, blue)
      influenced the properties of the microbody particles to form a distinct band
      sharply confined close to an equilibrium density of 1.25 g cm(-3) on sucrose
      gradients which was not observed in preparations from plant material raised in
      complete darkness. In preparations from all light-grown plants a special peak in
      the activity profile of malate dehydrogenase was found in the microbody fraction
      while it was lacking on gradients from dark-grown leaves. The heights of the
      activities of malate dehydrogenase as well as of the other enzymes found in the
      microbody fractions from plants grown in either far-red, red, or blue light
      differed in the same way as did the activities from total leaf homogenates. 4.
      Glycolate oxidation by segments of intact leaf tissue was higher with tissue from
      light- than from dark-grown plants, but after light treatments of different
      spectral quality its magnitude did not correspond to the extractable activities
      of glycolate oxidase. 

PMID- 24436026
TI  - A deficiency of hypoxanthine phosphoribosyltransferase in a sycamore callus
      resistant to azaguanine.
AB  - Sycamore (Acer pseudoplatanus L.) calluses resistant to azaguanine were isolated
      after mutagenesis with nitrosoguanidine. One callus SNC61 was highly variable in
      its growth on 10 MUg/ml azaguanine and it was concluded that its resistance was
      not due to a stable alteration in the callus. Another callus SNE31 was isolated
      after 4.5 months culture in 0.5 or 1 MUg/ml azaguanine which had a 10-fold
      increase in resistance to azaguanine. This was shown to be accompanied by a
      reduction to 50% of the normal level of hypoxanthine phosphoribosyltransferase
      (E.C.2.4.2.8). 

PMID- 24436027
TI  - The effect of leaf age on leaf resistance and CO2 exchange of the CAM plant
      Bryophyllum fedtschenkoi.
AB  - Leaves of different ages from the CAM (Crassulacean acid metabolism) plant
      Bryophyllum fedtschenkoi Hamet et Per. differ in their ability to accumulate
      titratable actidity during the night. Measurements of leaf resistance to water
      vapour diffusion and net CO2 exchange during the day and night show differing
      patterns of behaviour dependent upon leaf age. Young leaves do not exhibit CAM;
      they behave like typical mesophytes with low resistances and a net uptake of CO2
      during the day and a net output of CO2 at night. Mature leaves exhibit CAM and
      have high leaf resistances during the day and lower resistances at night but
      their pattern of CO2 exchange is complex, with a net output early in their day
      followed by a net uptake which continues at a reduced rate through the night.
      Intermediate, leaves are intermediate in their behaviour The presence of CAM in
      older leaves may simply be the result of increased cell vacuole size.Leaf
      resistance measurements are discussed in relation to the possible control of
      stomatal opening by substomatal CO2 concentrations. 

PMID- 24436028
TI  - Zinc in pollen and its incorporation into seeds.
AB  - A study on the distribution of radioactive zinc ((65)Zn) in flowers of Vicia faba
      L. and Nicotiana tabacum L. showed the highest activity, expressed as cpm/mg dry
      weight, in pollen Also, using a histochemical method, it was observed that a
      portion of the naturally occurring zinc present in pollen grains was transferred
      into their growing tubes during germination. Calculations in based on the
      specific activity in (65)Zn-labelled pollen grains and in seeds from flowers
      pollinated with this pollen showed that about 68% of the radioisotope content of
      the pollen was incorporated into the seeds. The significance of these results and
      the possible role of zinc in fertilization is discussed. 

PMID- 24436029
TI  - Renin-angiotensin-aldosterone-blockade is associated with decreased use of
      antidepressant therapy in patients with type 1 diabetes and diabetic nephropathy.
AB  - Hypertension and depression are frequent comorbidities of diabetes. Studies
      suggest that antihypertensive medication affecting the renin-angiotensin
      aldosterone system (RAAS) might also relieve depression. Whether this is also
      seen in patients with type 1 diabetes is not known. We therefore studied whether
      use of RAAS-modifying medication is associated with reduced antidepressant use in
      type 1 diabetes. In all, 1,705 participants in the FinnDiane Study were included
      (57 % men, mean age 46 +/- 11 years). Data on medications were obtained from the
      Drug Prescription Register. Based on their albumin excretion rate (AER), the
      patients were classified as having normal AER, microalbuminuria, or
      macroalbuminuria. Diabetic nephropathy was defined as macroalbuminuria or end
      stage renal disease (dialysis or renal transplant). A total of 8.4 and 10.9 % of
      patients with and without RAAS-modifying medication, respectively, had
      antidepressant medication purchases (NS). In logistic regression analysis, after
      adjusting for potential confounding factors, use of RAAS-modifying medication was
      not associated with antidepressant purchases. However, when patients with and
      without diabetic nephropathy were analyzed separately, RAAS-modifying medication
      was associated with lower frequency of antidepressant purchases among patients
      with established diabetic nephropathy. In conclusion, use of RAAS-modifying
      medication may improve mood in patients with type 1 diabetes and established
      diabetic nephropathy. 

PMID- 24436030
TI  - Impact of capped and uncapped abandoned leads on the heating of an MR-conditional
      pacemaker implant.
AB  - PURPOSE: To assess the risk of radiofrequency (RF)-induced heating in patients
      with MR-conditional pacemaker (PM) systems, in the presence of another lead
      abandoned from a previous implant. METHODS: Four commercial pacemaker leads were
      placed beside a MR-conditional PM system, inside a human trunk simulator. The
      phantom has been exposed to the RF generated by a 64 MHz body bird-cage coil
      (whole-body specific absorption rate [SAR] = 1 W/kg) and the induced heating was
      measured at the tip of the abandoned lead and of the MR-conditional implant.
      Configurations that maximize the coupling between the RF field and the leads have
      been tested, as well as realistic implant positions. RESULTS: Abandoned leads
      showed heating behaviors that strongly depend on the termination condition
      (abandoned-capped or saline exposed) and on the lead path (left or right
      positioning). Given a whole-body SAR = 1 W/kg, a maximum temperature rise of 17.6
      degrees C was observed. The presence of the abandoned lead modifies the RF
      heating profile of the MR-conditional implant: either an increase or a decrease
      in the induced heating at its lead tip can occur, mainly depending on the
      relative position of the two leads. Variations ranging from -63% to +69% with
      respect to the MR-conditional system alone were observed. CONCLUSION: These
      findings provide experimental evidence that the presence of an abandoned lead
      poses an additional risk for the patient implanted with a MR-conditional PM
      system. Our results support the current PM manufacturers' policy of conditioning
      the MR compatibility of their systems to the absence of abandoned leads
      (including leads from MR-conditional implants). From a clinical point of view, in
      such cases, the decision whether to perform the exam shall be based upon a
      risk/benefit evaluation, as in the case of conventional PM systems.

PMID- 24436031
TI  - Expression of PARP-1 and its active polymer PAR in prostate cancer and benign
      prostatic hyperplasia in Chinese patients.
AB  - BACKGROUND AND AIMS: Aberrant expression of PARP-1 has been reported in various
      human malignancies and was involved in the progression and metastasis of cancers.
      However, little is known about PARP-1 expression in prostate cancer (PCa). This
      study aimed to investigate the expression of PARP-1 and its active polymer
      poly(ADP-ribose) (PAR) in PCa and benign prostatic hyperplasia (BPH) tissues from
      Chinese patients. METHODS: The expression of PARP-1 and PAR in PCa and benign
      prostate hyperplasia tissues was assessed by immunohistochemistry in 78 PCa
      patients and 49 BPH patients. The relationship between the expression of PARP-1
      or PAR and clinicopathological parameters in PCa patients was also analyzed.
      RESULTS: Both the positive and strong positive expression rates of PARP-1 in PCa
      tissues were significantly higher than those in BPH tissues. Although spearman
      correlations analysis showed the over-expression of PARP-1 and PAR in PCa tissues
      was not correlated with age, serum PSA level and Gleason scores (GS), an
      increasing trend was observed between over-expression of PARP-1 or PAR and the
      PSA levels (TPSA >20 vs TPSA <=20) or GS grade (GS >=8 vs GS <=6). CONCLUSION:
      PARP-1 and PAR expression is markedly elevated in PCa than that in BPH tissues,
      which may implicate that PARP-1 and PAR are involved in the development of PCa,
      and the possible expansion in the use of poly(ADP-ribose) polymerase inhibitors
      for targeting therapy of PCa in select patients alone or combined with
      chemotherapy or radiation.

PMID- 24436032
TI  - Impact of CMS coverage decision on access to transcatheter aortic valve
      replacement.
AB  - OBJECTIVES: To assess the impact of the Centers for Medicare and Medicaid
      Services (CMS) national coverage determination (NCD) on access for patients with
      aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) in a
      tertiary care center. BACKGROUND: TAVR has given hope to patients with AS who are
      deemed inoperable. The effects of the NCD on access to patients with AS has not
      been evaluated. MATERIALS AND METHODS: A total of 94 inoperable AS patients were
      evaluated and treated from December 2011 through June of 2012 with TAVR. Patients
      who underwent transfemoral (TF) vs. non-TF access were compared. The CMS NCD was
      released on May 1, 2012 and on July 1, 2012, the nontransfemoral access program
      was put on hold due to lack of reimbursement. RESULTS: Patients in the TF (n =
      33) and non-TF access (n = 61) groups were similar in age (85.2 +/- 6.3 vs. 84.8
      +/- 6.6 P = 0.74) and STS mortality (9.38 +/- 5.33 vs. 7.91 +/- 3.69, P = 0.074).
      The iliofemoral arteries were larger diameter in the TF group (7.72 +/- 1.49 vs.
      6.21 +/- 1.78, P < 0.001) and males (7.39 +/- 1.81 vs. 6.1 +/- 1.61 P < 0.001).
      More women underwent valve implantation via non-TF access (73 vs. 23%, P = 0.03).
      After the NCD, 21 patients who previously qualified for non-TF TAVR would not be
      reimbursed by CMS. Four died soon after. CONCLUSIONS: After the NCD, the
      proportion of inoperable patients with severe AS that can be treated with TAVR
      was greatly reduced due the lack of reimbursement for TAVR via non-TF access.
      This effect is particularly pronounced in women. (c) 2014 Wiley Periodicals, Inc.

PMID- 24436033
TI  - Miniaturized approach for excipient selection during the development of oral
      solid dosage form.
AB  - The present study introduces a miniaturized high-throughput platform to
      understand the influence of excipients on the performance of oral solid dosage
      forms during early drug development. Wet massing of binary mixtures of the model
      drug (sodium naproxen) and representative excipients was followed by sieving,
      drying, and compaction of the agglomerated material. The mini-compacts were
      subjected to stability studies at 25 degrees C/5% relative humidity (RH), 25
      degrees C/60% RH and 40 degrees C/75% RH for 3 months. The physical stability of
      the drug was affected by the storage condition and by the characteristics of the
      excipients, whereas all the samples were chemically stable. Force-distance curves
      obtained during the compression of agglomerated material were used for the
      comparison of compressibility of different drug-excipient mixtures. The
      agglomerated drug-excipient mixtures were also subjected to studies of the
      dissolution trend under sequential pH conditions to simulate pH environment of
      gastrointestinal tract. Major factors affecting the dissolution behavior were the
      diffusion layer pH of the binary mixtures and the ability of the excipients to
      alter the diffusion layer thickness. The proposed approach can be used for
      excipient selection and for early-stage performance testing of active
      pharmaceutical ingredient intended for oral solid dosage form.

PMID- 24436035
TI  - Assessing impact of differential symptom functioning on post-traumatic stress
      disorder (PTSD) diagnosis.
AB  - This article explores the generalizability of the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for post
      traumatic stress disorder (PTSD) to various subpopulations. Besides identifying
      the differential symptom functioning (also referred to as differential item
      functioning [DIF]) related to various background variables such as gender,
      marital status and educational level, this study emphasizes the importance of
      evaluating the impact of DIF on population inferences as made in health surveys
      and clinical trials, and on the diagnosis of individual patients. Using a sample
      from the National Comorbidity Study-Replication (NCS-R), four symptoms for
      gender, one symptom for marital status, and three symptoms for educational level
      were significantly flagged as DIF, but their impact on diagnosis was fairly
      small. We conclude that the DSM-IV diagnostic criteria for PTSD do not produce
      substantially biased results in the investigated subpopulations, and there should
      be few reservations regarding their use. Further, although the impact of DIF
      (i.e. the influence of differential symptom functioning on diagnostic results)
      was found to be quite small in the current study, we recommend that
      diagnosticians always perform a DIF analysis of various subpopulations using the
      methodology presented here to ensure the diagnostic criteria is valid in their
      own studies.

PMID- 24436034
TI  - D-serine and serine racemase are localized to neurons in the adult mouse and
      human forebrain.
AB  - D-Serine, a co-agonist at the NMDA receptor (NMDAR), is synthesized from L-serine
      by the enzyme serine racemase (SR), which is heavily expressed in the forebrain.
      Although SR was originally reported to be localized exclusively to astrocytes,
      recent conditional knock out results demonstrate that little SR is expressed in
      forebrain astrocytes. As a consequence, the cellular location of its product, D
      serine, in the brain is also uncertain. Immunocytochemistry now indicates that SR
      is expressed primarily in forebrain glutamatergic neurons with the remainder in
      GABAergic interneurons. We utilized SR deficient (SR-/-) mice, which have <15 %
      of normal D-serine levels, to validate and optimize a D-serine
      immunohistochemical method. Nearly all of the D-serine in neocortex and
      hippocampus (HP) is found in neurons, with virtually no D-serine co-localizing
      with two astrocyte markers. Interestingly, only a subset of the D-serine positive
      neurons contained SR in the neocortex and HP. Greater than half of the D-serine
      positive neurons were GABAergic interneurons, with a majority of these neurons
      containing parvalbumin and/or somatostatin. Only ~25-40 % of interneurons
      expressed SR in the neocortex and HP. Finally, we demonstrate in human post
      mortem neocortex that SR is found in both excitatory and inhibitory neurons, but
      not in S100beta-containing astrocytes. In sum, these findings conclusively
      demonstrate that the majority of D-serine is both synthesized and stored in
      neurons. It will be important to determine the functional significance for the
      separation of synthesis and storage of D-serine in neurons, as well as the
      presence of this NMDAR co-agonist in GABAergic interneurons.

PMID- 24436036
TI  - Reversible light-driven polymerization of polyoxometalate tethered with coumarin
      molecules.
AB  - A new photosensitive polyoxometalate (POM) organic-inorganic hybrid compound has
      been prepared by covalently tethering coumarin moieties onto a Mn-Anderson
      cluster. This compound has been fully characterized by (1)H NMR, (13)C NMR, FTIR,
      and UV/Vis spectroscopy, and ESI-MS. This organic-inorganic hybrid compound can
      undergo reversible light-driven polymerization and this process has been
      characterized in detail.

PMID- 24436037
TI  - The foodomics approach for the evaluation of protein bioaccessibility in
      processed meat upon in vitro digestion.
AB  - The present work describes a foodomics protocol coupling an in vitro static
      simulation of digestion to a combination of omics techniques, to grant an
      overview of the protein digestibility of a meat-based food, namely Bresaola. The
      proteolytic activity mediated by the digestive enzymes is evaluated through
      Bradford and SDS-PAGE assays, combined to NMR relaxometry and spectroscopy, to
      obtain information ranging from the microscopic to the molecular level,
      respectively. The simple proteomics tool adopted here points out that a clear
      increase of bioaccessible proteins occurs in the gastric phase, rapidly
      disappearing during the following duodenal digestion. However, SDS-PAGE and the
      Bradford assay cannot follow the fate of the digested proteins when the products
      are sized <5 kDa. Conversely, NMR spectroscopy is able to capture the overall
      molecular profile of small fragments and peptides, which are mainly formed during
      the duodenal phase, thus giving the kinetics of the whole digestion process. Time
      domain NMR relaxometry, finally, detects the swelling phenomenon occurring during
      the gastric phase, when the digestion fluid enters the meat matrix. 

PMID- 24436038
TI  - Greetings from the incoming editor-in-chief.

PMID- 24436039
TI  - Comparative anatomy, physiology, and mechanisms of disease production of the
      esophagus, stomach, and small intestine.
AB  - The alimentary system may be thought of as an open-ended tube within a tube that
      begins at the oral cavity and ends at the anus. Gastrointestinal lumens are
      potential spaces that accommodate ingested substances and are lined by polarized
      epithelium that is smooth and shiny (with the exception of the rumen) when
      healthy and intact. Because xenobiotics most frequently enter the body via
      ingestion, the gastrointestinal system and its ancillary glands are the first
      line of defense against foreign materials and pathogens of all types. The
      anatomic, biochemical, physical, secretory, and endocrinologic properties of the
      epithelium, resident, and blood-borne effector cells, microbiota, genetic
      polymorphisms, and gut-associated lymphoid tissue (which comprises one-quarter of
      the body's total) must be physically or functionally altered for diarrhea to
      occur. The average person ingests 700 tons of antigens in their lifetime. That
      enteritis does not occur more often than it does is testimony to the efficacy of
      gastrointestinal protective systems. 

PMID- 24436040
TI  - The role of the pathologist in GLP studies.
AB  - This continuing education course presented at the Society of Toxicologic
      Pathology's 31st Annual Symposium explored and defined the many roles that
      toxicologic pathologists serve Good Laboratory Practice (GLP)-conducted
      toxicology and carcinogenicity studies. 

PMID- 24436041
TI  - Design of affinity peptides from natural protein ligands: A study of the cardiac
      troponin complex.
AB  - We describe a general strategy for the design and discovery of affinity peptides
      for a protein from its natural ligands. Our approach is guided by protein-protein
      interactions in natural systems and focuses on the hetero-trimeric complex of
      cardiac troponin I (cTnI), C (cTnC) and T (cTnT). A key premise of this work is
      that cTnC and cTnT, owing to their innate ability to bind cTnI, are potential
      templates for the design and discovery of cTnI-binding peptides. Relying only on
      the knowledge of primary sequences of cTnC and cTnT, we designed a library of
      short overlapping peptides that span the entirety of cTnC and cTnT and tested
      them for binding to cTnI. We were successful in identifying several peptides that
      display high affinity (1-100 nM) for cTnI. The specific implication of this work
      is that mimicking natural protein-protein interactions is an excellent starting
      point for the discovery and rational design of peptide ligands. The knowledge of
      secondary or tertiary structures of the proteins involved is not a necessary
      precondition for this approach. Nevertheless, we show that structural information
      can be used to validate the results of a fragment-based peptide design, and can
      be potentially beneficial for refining the lead candidates. Our approach is
      broadly applicable to any protein with at least one natural binding ligand with
      known primary sequence. For protein targets with multiple natural ligands, this
      approach can potentially yield several distinct affinity peptides capable of
      simultaneously binding the target protein via orthogonal modes or at
      complementary interfaces.

PMID- 24436042
TI  - Translation of structure-activity relationships from cyclic mixed efficacy opioid
      peptides to linear analogues.
AB  - Most opioid analgesics used in the treatment of pain are mu opioid receptor (MOR)
      agonists. While effective, there are significant drawbacks to opioid use,
      including the development of tolerance and dependence. However, the
      coadministration of a MOR agonist with a delta opioid receptor (DOR) antagonist
      slows the development of MOR-related side effects, while maintaining analgesia.
      We have previously reported a series of cyclic mixed efficacy MOR agonist/DOR
      antagonist ligands. Here we describe the transfer of key features from these
      cyclic analogs to linear sequences. Using the linear MOR/DOR agonist, Tyr-DThr
      Gly-Phe-Leu-Ser-NH2 (DTLES), as a lead scaffold, we replaced Phe(4) with bulkier
      and/or constrained aromatic residues shown to confer DOR antagonism in our cyclic
      ligands. These replacements failed to confer DOR antagonism in the DTLES analogs,
      presumably because the more flexible linear ligands can adopt binding poses that
      will fit in the narrow binding pocket of the active conformations of both MOR and
      DOR. Nonetheless, the pharmacological profile observed in this series, high
      affinity and efficacy for MOR and DOR with selectivity relative to KOR, has also
      been shown to reduce the development of unwanted side effects. We further
      modified our lead MOR/DOR agonist with a C-terminal glucoserine to improve
      bioavailability. The resulting ligand displayed high efficacy and potency at both
      MOR and DOR and no efficacy at KOR.

PMID- 24436043
TI  - Enhancement of the helical content and stability induced in a linear oligopeptide
      by an i, i+4 intramolecularly double stapled, overlapping, bicyclic [31, 22, 5]
      (E)ene motif.
AB  - Two consecutive i, i+4 intramolecular, side chain-to-side chain,
      macrocyclizations of different type carried out on a preformed, partially helical
      peptide result in a largely predominant, double stapled, overlapping, bicyclic
      [31,22,5]-(E)ene motif. A detailed ECD and NMR conformational study revealed a
      significant enhancement of the original helical content and stability,
      accompanied by an increase of the alpha-helix amount over that of the 3(10)
      helix.

PMID- 24436045
TI  - Another year behind us.

PMID- 24436046
TI  - Lifelong exposure to methylmercury disrupts stress-induced corticosterone
      response in zebra finches (Taeniopygia guttata).
AB  - Mercury can disrupt the endocrine systems of mammals and fish, but little is
      known about its effects on avian hormones. The authors employed an experimental
      manipulation to show that methylmercury suppresses the stress-induced
      corticosterone response in birds, an effect previously unreported in the
      literature. Corticosterone regulates many normal metabolic processes, such as the
      maintenance of proper blood glucose levels during stressful daily fasting; an
      inability to increase corticosterone levels in response to stressors renders a
      bird less able to face a wide array of environmental challenges. The authors
      studied reproductively mature zebra finches that had been exposed to 0.0 ug/g,
      0.3 ug/g, 0.6 ug/g, 1.2 ug/g, or 2.4 ug/g (wet wt) dietary methylmercury
      throughout their life (i.e., from the egg onward). In contrast to some field
      studies, the present study found no significant change in baseline plasma
      corticosterone concentrations attributable to chronic methylmercury exposure.
      However, a comparison between the baseline corticosterone levels and levels after
      30 min of handling stress revealed that the ability of birds to mount a stress
      response was reduced with increasing blood total mercury concentration. These
      results are consistent with adrenal corticoid disruption caused by chronic
      mercury exposure and mirror a similar study on free-living nestling songbirds
      exposed to environmental mercury.

PMID- 24436047
TI  - Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of
      alterations affecting a common genetic axis in fusion-positive and fusion
      negative tumors.
AB  - Despite gains in survival, outcomes for patients with metastatic or recurrent
      rhabdomyosarcoma remain dismal. In a collaboration between the National Cancer
      Institute, Children's Oncology Group, and Broad Institute, we performed whole
      genome, whole-exome, and transcriptome sequencing to characterize the landscape
      of somatic alterations in 147 tumor/normal pairs. Two genotypes are evident in
      rhabdomyosarcoma tumors: those characterized by the PAX3 or PAX7 fusion and those
      that lack these fusions but harbor mutations in key signaling pathways. The
      overall burden of somatic mutations in rhabdomyosarcoma is relatively low,
      especially in tumors that harbor a PAX3/7 gene fusion. In addition to previously
      reported mutations in NRAS, KRAS, HRAS, FGFR4, PIK3CA, and CTNNB1, we found novel
      recurrent mutations in FBXW7 and BCOR, providing potential new avenues for
      therapeutic intervention. Furthermore, alteration of the receptor tyrosine
      kinase/RAS/PIK3CA axis affects 93% of cases, providing a framework for genomics
      directed therapies that might improve outcomes for patients with
      rhabdomyosarcoma. SIGNIFICANCE: This is the most comprehensive genomic analysis
      of rhabdomyosarcoma to date. Despite a relatively low mutation rate, multiple
      genes were recurrently altered, including NRAS, KRAS, HRAS, FGFR4, PIK3CA,
      CTNNB1, FBXW7, and BCOR. In addition, a majority of rhabdomyosarcoma tumors alter
      the receptor tyrosine kinase/RAS/PIK3CA axis, providing an opportunity for
      genomics-guided intervention.

PMID- 24436050
TI  - Erythropoietin enhances mitochondrial biogenesis in cardiomyocytes exposed to
      chronic hypoxia through Akt/eNOS signalling pathway.
AB  - Adaptation of cardiomyocytes to chronic hypoxia in cyanotic patients remains
      unclear. Mitochondrial biogenesis is enhanced in myocardium from cyanotic
      patients, which is possibly an adaptive response. Erythropoietin (EPO) in blood
      and its receptor (EPOR) on cardiomyocytes are upregulated by chronic hypoxia,
      suggesting that EPO-EPOR interaction is increased, which is inferred to
      positively regulate mitochondrial biogenesis through protein kinase B
      (Akt)/endothelial nitric oxide synthase (eNOS) signalling pathway. H9c2
      cardiomyocytes were exposed to hypoxia (1% O(2)) for 1 week and treated with
      different doses of recombinant human erythropoietin (rhEPO). Mitochondrial
      number, mitochondrial DNA (mtDNA) copy number and peroxisome proliferator
      activated receptor gamma coactivator alpha (PGC-1alpha) mRNA expression increased
      in a dose-dependent manner induced by rhEPO. Akt and eNOS were significantly
      phosphorylated by rhEPO. Both blocking Akt with Wortmannin and silencing eNOS
      expression with shRNA plasmid decreased the mtDNA copy number and PGC-1alpha mRNA
      expression induced by rhEPO. Blocking Akt was associated with the decreased
      phosphorylation of Akt and eNOS. RNA interference led to a reduction in the total
      and phosphorylated proteins of eNOS. Thus EPO enhances mitochondrial biogenesis
      in cardiomyocytes exposed to chronic hypoxia, at least partly through Akt/eNOS
      signalling, which might be an adaptive mechanism of cardiomyocytes associated
      with the increased EPO-EPOR interaction in patients with cyanotic congenital
      heart disease (CCHD).

PMID- 24436049
TI  - Tolerance of whole-genome doubling propagates chromosomal instability and
      accelerates cancer genome evolution.
AB  - The contribution of whole-genome doubling to chromosomal instability (CIN) and
      tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells
      from a stable diploid colon cancer progenitor to investigate how a genome
      doubling event affects genome stability over time. Rare cells that survive genome
      doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid
      cells do not exhibit increased frequencies of structural or numerical CIN per
      chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a
      doubling of chromosome aberrations per cell, allows chromosome abnormalities to
      evolve specifically in tetraploids, recapitulating chromosomal changes in
      genomically complex colorectal tumors. Finally, a genome-doubling event is
      independently predictive of poor relapse-free survival in early-stage disease in
      two independent cohorts in multivariate analyses [discovery data: hazard ratio
      (HR), 4.70, 95% confidence interval (CI), 1.04-21.37; validation data: HR, 1.59,
      95% CI, 1.05-2.42]. These data highlight an important role for the tolerance of
      genome doubling in driving cancer genome evolution. SIGNIFICANCE: Our work sheds
      light on the importance of whole-genome-doubling events in colorectal cancer
      evolution. We show that tetraploid cells undergo rapid genomic changes and
      recapitulate the genetic alterations seen in chromosomally unstable tumors.
      Furthermore, we demonstrate that a genome-doubling event is prognostic of poor
      relapse-free survival in this disease type.

PMID- 24436048
TI  - Rapid induction of apoptosis by PI3K inhibitors is dependent upon their transient
      inhibition of RAS-ERK signaling.
AB  - The effects of selective phosphoinositide 3-kinase (PI3K) and AKT inhibitors were
      compared in human tumor cell lines in which the pathway is dysregulated. Both
      caused inhibition of AKT, relief of feedback inhibition of receptor tyrosine
      kinases, and growth arrest. However, only the PI3K inhibitors caused rapid
      induction of cell death. In seeking a mechanism for this phenomenon, we found
      that PI3K inhibition, but not AKT inhibition, causes rapid inhibition of wild
      type RAS and of RAF-MEK-ERK signaling. Inhibition of RAS-ERK signaling is
      transient, rebounding a few hours after drug addition, and is required for rapid
      induction of apoptosis. Combined MEK and AKT inhibition also promotes cell death,
      and in murine models of HER2(+) cancer, either pulsatile PI3K inhibition or
      combined MEK and AKT inhibition causes tumor regression. We conclude that PI3K is
      upstream of RAS and AKT and that pulsatile inhibition of both pathways is
      sufficient for effective antitumor activity. 

PMID- 24436051
TI  - Phytohemagglutinin from Phaseolus vulgaris (PHA-E) displays a novel glycan
      recognition mode using a common legume lectin fold.
AB  - Phytohemagglutinin from Phaseolus vulgaris (PHA-E), a legume lectin, has an
      unusual specificity toward biantennary galactosylated N-glycan with bisecting N
      acetylglucosamine (GlcNAc). To investigate the interaction in detail, we have
      solved the crystal structures of PHA-E without ligand and in complex with
      biantennary N-glycan derivatives. PHA-E interacts with the trisaccharide unit
      (Galbeta1-4GlcNAcbeta1-2Man) in a manner completely different from that of
      mannose/glucose-specific legume lectins. The inner mannose residue binds to a
      novel site on the protein, and its rotation is opposite to that occurring in the
      monosaccharide-binding site of other lectins around the sugar O3 axis. Saturation
      transfer difference NMR using biantennary di-galactosylated and bisected glycans
      reveals that PHA-E interacts with both antennas almost equally. The unique
      carbohydrate interaction explains the glycan-binding specificity and high
      affinity. 

PMID- 24436052
TI  - Heterogeneous cellular distribution of glutamate dehydrogenase in brain and in
      non-neural tissues.
AB  - Mammalian glutamate dehydrogenase (GDH) is an evolutionarily conserved enzyme
      central to the metabolism of glutamate, the main excitatory transmitter in
      mammalian CNS. Its activity is allosterically regulated and thought to be
      controlled by the need of the cell for ATP. While in most mammals, GDH is encoded
      by a single GLUD1 gene that is widely expressed (housekeeping; hGDH1 in the
      human), humans and other primates have acquired via retroposition a GLUD2 gene
      encoding an hGDH2 isoenzyme with distinct functional properties and tissue
      expression profile. Whereas hGDH1 shows high levels of expression in the liver,
      hGDH2 is expressed in human testis, brain and kidney. Recent studies have
      provided significant insight into the functional adaptation of hGDH2. This
      includes resistance to GTP control, enhanced sensitivity to inhibition by
      estrogens and other endogenous allosteric effectors, and ability to function in a
      relatively acidic environment. While inhibition of hGDH1 by GTP, derived from
      Krebs cycle, represents the main mechanism by which the flux of glutamate through
      this pathway is regulated, dissociation of hGDH2 from GTP control may provide a
      biological advantage by permitting enzyme function independently of this energy
      switch. Also, the relatively low optimal pH for hGDH2 is suited for transmitter
      glutamate metabolism, as glutamate uptake by astrocytes leads to significant
      mitochondrial acidification. Although mammalian GDH is a housekeeping enzyme, its
      levels of expression vary markedly among the various tissues and among the
      different types of cells that constitute the same organ. In this paper, we will
      review existing evidence on the cellular and subcellular distribution of GDH in
      neural and non-neural tissues of experimental animals and humans, and consider
      the implications of these findings in biology of these tissues. Special attention
      is given to accumulating evidence that glutamate flux through the GDH pathway is
      linked to cell signaling mechanisms that may be tissue-specific. 

PMID- 24436053
TI  - Processing visual words with numbers: electrophysiological evidence for semantic
      activation.
AB  - Perea, Dunabeitia, and Carreiras (Journal of Experimental Psychology: Human
      Perception and Performance 34:237-241, 2008) found that LEET stimuli, formed by a
      mixture of digits and letters (e.g., T4BL3 instead of TABLE), produced priming
      effects similar to those for regular words. This finding led them to conclude
      that LEET stimuli automatically activate lexical information. In the present
      study, we examined whether semantic activation occurs for LEET stimuli by using
      an electrophysiological measure called the N400 effect. The N400 effect, also
      known as the mismatch negativity, reflects detection of a mismatch between a word
      and the current semantic context. This N400 effect could occur only if the LEET
      stimulus had been identified and processed semantically. Participants determined
      whether a stimulus (word or LEET) was related to a given category (e.g., APPLE or
      4PPL3 belongs to the category "fruit," but TABLE or T4BL3 does not). We found
      that LEET stimuli produced an N400 effect similar in magnitude to that for
      regular uppercase words, suggesting that LEET stimuli can access meaning in a
      manner similar to words presented in consistent uppercase letters. 

PMID- 24436054
TI  - Whither the psychosis-neurosis borderline.

PMID- 24436055
TI  - Transcription of the human sodium channel SCN1A gene is repressed by a
      scaffolding protein RACK1.
AB  - Voltage-gated sodium channel alpha subunit type I (Nav1.1, encoded by SCN1A gene)
      plays a critical role in the initiation of action potential in the central
      nervous system. Downregulated expression of SCN1A is believed to be associated
      with epilepsy. Here, we found that the SCN1A promoter (P1c), located at the 5'
      untranslated exon 1c, drove the reporter gene expression in human NT2 cells, and
      a region between nt +53 and +62 downstream of the P1c promoter repressed the
      promoter activity. Further analyses showed that a scaffolding protein RACK1
      (receptor for activated C kinase 1) was involved in binding to this silencer.
      Knockdown of RACK1 expression in NT2 cells deprived the repressive role of the
      silencer on the P1c promoter and increased SCN1A transcription, suggesting the
      potential involvement of RACK1 in negatively regulating SCN1A transcription via
      interaction with the silencer. Furthermore, we demonstrated that the binding of
      the protein complex including RACK1 to the SCN1A promoter motif was decreased in
      neuron-like differentiation of the NT2 cells induced by retinoic acid and
      resulted in the upregulation of SCN1A transcription. Taken together, this study
      reports a novel role of RACK1 in regulating SCN1A expression that participates in
      retinoic acid-induced neuronal differentiation of NT2 cells. 

PMID- 24436057
TI  - Synthesis, NMR structural characterization and molecular modeling of substituted
      thiosemicarbazones and semicarbazones using DFT calculations to prove the
      syn/anti isomer formation.
AB  - Thiosemicarbazones possessing electron-donating and electron-withdrawing groups
      were prepared, and their spectral characteristics determined. In all cases, the
      spectra showed that one isomer was formed, allowing further functionalization to
      molecules of biological interest. We provide NMR data for some of the
      thiosemicarbazones and semicarbazones. We also provide evidence that for 2
      pyridyl thiosemicarbazone, the syn isomer slowly converts into the anti isomer in
      dimethyl sulfoxide solvent with first-order kinetics. Molecular modeling and
      density functional theory calculations confirmed these observations.

PMID- 24436056
TI  - Amyloid beta-peptide 1-42 modulates the proliferation of mouse neural stem cells:
      upregulation of fucosyltransferase IX and notch signaling.
AB  - Amyloid beta-peptides (Abetas) aggregate to form amyloid plaques, also known as
      senile plaques, which are a major pathological hallmark of Alzheimer's disease
      (AD). Abetas are reported to possess proliferation effects on neural stem cells
      (NSCs); however, this effect remains controversial. Thus, clarification of their
      physiological function is an important topic. We have systematically evaluated
      the effects of several putative bioactive Abetas (Abeta1-40, Abeta1-42, and
      Abeta25-35) on NSC proliferation. Treatment of NSCs with Abeta1-42 significantly
      increased the number of those cells (149 +/- 10 %). This was not observed with
      Abeta1-40 which did not have any effects on the proliferative property of NSC.
      Abeta25-35, on the other hand, exhibited inhibitory effects on cellular
      proliferation. Since cell surface glycoconjugates, such as glycolipids,
      glycoproteins, and proteoglycans, are known to be important for maintaining cell
      fate determination, including cellular proliferation, in NSCs and they undergo
      dramatic changes during differentiation, we examined the effect of Abetas on a
      number of key glycoconjugate metabolizing enzymes. Significantly, we found for
      the first time that Abeta1-42 altered the expression of several key
      glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9),
      sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and
      mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the
      Lewis X carbohydrate epitope, which is known to be expressed in stem cells.
      Abeta1-42 also stimulated the Notch1 intracellular domain (NICD) by upregulation
      of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Abeta1-42
      upregulates NSC proliferation by modulating the expression of several glycogenes
      involved in Notch signaling.

PMID- 24436058
TI  - Fluorescence enhancement of europium (III) perchlorate by 1,10-phenanthroline on
      the 1-(naphthalen-2-yl)-2-(phenylsulthio)ethanone complex and luminescence
      mechanism.
AB  - A novel ligand, 1-(naphthalen-2-yl)-2-(phenylsulthio)ethanone was synthesized
      using a new method and its two europium (Eu) (III) complexes were synthesized.
      The compounds were characterized by elemental analysis, coordination titration
      analysis, molar conductivity, infrared, thermo gravimetric analyzer-differential
      scanning calorimetry (TGA-DSC), (1)H NMR and UV spectra. The composition was
      suggested as EuL5 . (ClO4)3 . 2H2O and EuL4 . phen(ClO4)3 . 2H2O (L =
      C(10)H(7)COCH(2)SOC(6)H(5)). The fluorescence spectra showed that the Eu(III)
      displayed strong characteristic metal-centered fluorescence in the solid state.
      The ternary rare earth complex showed stronger fluorescence intensity than the
      binary rare earth complex in such material. The strongest characteristic
      fluorescence emission intensity of the ternary system was 1.49 times as strong as
      that of the binary system. The phosphorescence spectra were also discussed.

PMID- 24436059
TI  - Exposure to chrysotile mining dust and digestive cancer mortality in a Chinese
      miner/miller cohort.
AB  - OBJECTIVES: To examine mortality from digestive cancers in a Chinese miner cohort
      and to explore the exposure-response relationship between chrysotile mining dust
      and site-specific digestive cancers. METHODS: A cohort of 1539 asbestos miners
      was followed for 26 years. Information on vital status and death causes was
      collected from personnel records and hospitals. Underlying causes of death from
      cancers were determined by combination of clinical manifestations and
      pathological confirmation. Individual cumulative dust exposures were estimated
      based on periodic dust measurements of different workshops, individuals' job
      title and employment duration, and treated as a time-dependent variable.
      Standardised mortality ratios (SMR) were calculated according to Chinese national
      data and stratified by exposure (levels 1-3, from low to high). Cox proportional
      hazard models were constructed to estimate HRs in relation to cumulative exposure
      with adjustment of smoking. RESULTS: Fifty-one deaths from digestive cancers were
      identified in the cohort, giving an SMR of 1.45 (95% CI 1.10 to 1.90). There was
      a clear exposure-response relationship between asbestos dust exposure and
      mortality from stomach cancer, with SMR of 2.39 (95% CI 1.02 to 5.60) and 6.49
      (2.77 to 15.20) at exposure levels 2 and 3, respectively. The clear relationship
      remained in multivariate analysis, in which workers at the highest exposure level
      had HRs of 12.23 (95% CI 8.74 to 17.12). In addition, excess mortality from
      oesophageal and liver cancers was also observed at high exposure levels.
      CONCLUSIONS: This study provides additional evidence for the association between
      exposure to chrysotile mining dust and excess mortality from digestive cancers,
      particularly stomach cancer.

PMID- 24436060
TI  - The psychological effects of improvised explosive devices (IEDs) on UK military
      personnel in Afghanistan.
AB  - OBJECTIVE: To explore the psychological consequences of improvised explosive
      device (IED) exposure as IEDs have been the greatest threat to UK military
      personnel in Afghanistan though the mental health consequences of IED exposure
      are largely unknown. METHOD: Deployed UK military personnel completed a survey
      while deployed in Afghanistan. Combat personnel and those dealing specifically
      with the IED threat were compared with all other deployed personnel; the
      relationship between IED exposure, general combat experiences, Post Traumatic
      Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C) and General Health
      Questionnaire scores were evaluated. RESULTS: The response rate was 98% (n=2794).
      Half reported IED-related concerns, a third experienced exploding IEDs and a
      quarter gave medical aid to IED casualties. Combat and counter-IED threat
      personnel had higher levels of IED exposure than other deployed personnel. 18.8%
      of personnel who witnessed exploding IEDs scored positive for common mental
      disorder (General Health Questionnaire-12 scores >=4) and 7.6% scored positive
      for probable PTSD symptoms (PTSD Checklist-Civilian Version scores >=44). After
      adjusting for general combat exposure and other observed confounders, PTSD
      symptoms were associated with IED exposure whereas common mental disorder
      symptoms were not. IED exposure, IED-related concerns and functional impairment
      accumulated during deployment but functional impairment was related to factors
      other than IED exposure alone. CONCLUSIONS: In Afghanistan, a substantial
      proportion of personnel were exposed to exploding IEDs however, the majority of
      exposed personnel were psychologically healthy. Psychological effects were
      similar for combat personnel and those dealing specifically with the IED threat
      but both groups were at greater psychological risk than other deployed personnel.

PMID- 24436061
TI  - The association between ambient exposure to organophosphates and Parkinson's
      disease risk.
AB  - OBJECTIVES: There is a general consensus that pesticides are involved in the
      aetiology of Parkinson's disease (PD), although associations between specific
      pesticides and the risk of developing PD have not been well studied. This study
      examines the risk of developing PD associated with specific organophosphate (OP)
      pesticides and their mechanisms of toxicity. METHODS: This case-control study
      uses a geographic information system-based exposure assessment tool to estimate
      ambient exposure to 36 commonly used OPs from 1974 to 1999. All selected OPs were
      analysed individually and also in groups formed according to their presumed
      mechanisms of toxicity. RESULTS: The study included 357 incident PD cases and 752
      population controls living in the Central Valley of California. Ambient exposure
      to each OP evaluated separately increased the risk of developing PD. However,
      most participants were exposed to combinations of OPs rather than a single
      pesticide. Risk estimates for OPs grouped according to different presumed
      functionalities and toxicities were similar and did not allow us to distinguish
      between them. However, we observed exposure-response patterns with exposure to an
      increasing number of OPs. CONCLUSIONS: This study adds strong evidence that OPs
      are implicated in the aetiology of idiopathic PD. However, studies of OPs at low
      doses reflective of real-world ambient exposure are needed to determine the
      mechanisms of neurotoxicity.

PMID- 24436062
TI  - Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected
      adults: prospective analysis of 435 liver biopsy pairs.
AB  - Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection is
      associated with progressive liver disease. However, the rate of progression is
      variable and the ability to differentiate patients with stable versus progressive
      HCV disease is limited. The objective of this study was to assess the incidence
      of and risk factors for fibrosis progression in a prospective cohort of
      coinfected patients. Overall, 435 liver biopsy pairs from 282 patients without
      cirrhosis were analyzed. Biopsies were scored according to the METAVIR system by
      a single pathologist blind to biopsy sequence. Fibrosis progression was defined
      as an increase of at least one METAVIR fibrosis stage between paired biopsies.
      The majority of patients were African American (84.8%), male (67.7%), and
      infected with HCV genotype 1 (93.4%). On initial biopsy, no or minimal fibrosis
      was identified in 243 patients (86%). The median interval between biopsies was
      2.5 years. Fibrosis progression was observed in 97 of 282 (34%) patients and 149
      of 435 (34%) biopsy pairs. After adjustment, greater body mass index (adjusted
      odds ratio [aOR]: 1.04 per 1 unit increase), diabetes (aOR: 1.56), and hepatic
      steatosis (aOR: 1.78) at the time of initial biopsy were marginally associated
      with subsequent fibrosis progression. Between biopsies, elevated serum aspartate
      and alanine aminotransferase (AST, ALT) (aOR AST: 3.34, ALT: 2.18 for >25% values
      >100 U/L versus <25% values >100 U/L) were strongly associated with fibrosis
      progression. CONCLUSION: Fibrosis progression is common among HIV/HCV coinfected
      patients; these data suggest that progression can be rapid. Persistent elevations
      in serum transaminase levels may serve as important noninvasive markers to
      identify subsets of patients who are more likely to progress and thus warrant
      closer monitoring and consideration of HCV treatment.

PMID- 24436064
TI  - Crenotalea thermophila gen. nov., sp. nov., a member of the family
      Chitinophagaceae isolated from a hot spring.
AB  - A thermophilic aerobic bacterium designated strain STH-1-Y1(T) was isolated from
      sulfur-turf in a Japanese hot spring (Okuhodaka hot spring, Gifu Pref.). Colonies
      of strain STH-1-Y1(T) were yellow and low convex morphology with a slightly
      irregular fringe. Cells were slender long rods, 0.4-0.6 um wide and 1.2-3.0 um
      long. The isolate was an obligate aerophilic organism, and could not grow by
      fermentation or nitrate respiration. The isolate had a thermophilic trait, and
      could grow at 35-60  degrees C and pH 5.5-7.5; maximum growth occurred at 55 
      degrees C and pH 7.0 with a doubling time of 1.9 h. The Biolog and API tests
      suggested that strain STH-1-Y1(T) was able to use various sugars such as glucose,
      lactose, mannose, maltose, trehalose, cellobiose and sucrose, but could not use
      sugar alcohols other than glycerol, i.e. adonitol, arabitol, erythritol,
      inositol, mannitol, sorbitol and xylitol. Lactate and glutamate could be used,
      but other fatty acids, i.e. acetate, citrate, propionate and succinate could not.
      Gelatin, casein, starch and glycogen were hydrolysed, but neither chitin nor agar
      was degraded. Cells lacked flexirubin and showed oxidase and catalase activities.
      The major respiratory quinone was menaquinone-7 (MK-7), and major cellular fatty
      acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C17 : 0 and anteiso-C15 : 0. No
      unsaturated fatty acids were detected. Phylogenetic analysis based on 16S rRNA
      gene sequences revealed that strain STH-1-Y1(T) was closely related to the family
      Chitinophagaceae within the phylum Bacteroidetes. However, the isolate was evenly
      distant from all members in this family with sequence similarities of 87-89 %.
      These significantly low sequence similarities strongly suggested that strain STH
      1-Y1(T) represents a novel species in a new genus of the family Chitinophagaceae
      within the phylum Bacteroidetes. Based on phenotypic and phylogenetic
      characteristics, the name Crenotalea thermophila gen. nov., sp. nov. is proposed.
      The type strain of the type species is STH-1-Y1(T) ( = JCM 11541(T) = DSM
      14807(T)). 

PMID- 24436065
TI  - Carboxylicivirga gen. nov. in the family Marinilabiliaceae with two novel
      species, Carboxylicivirga mesophila sp. nov. and Carboxylicivirga taeanensis sp.
      nov., and reclassification of Cytophaga fermentans as Saccharicrinis fermentans
      gen. nov., comb. nov.
AB  - Two facultatively anaerobic mesophilic bacteria, strains MEBiC 07026(T) and MEBiC
      08903(T), were isolated from two different tidal flat sediments and both strains
      showed approximately 92.2 % 16S rRNA gene sequence similarity with [Cytophaga]
      fermentans DSM 9555(T). 16S rRNA gene sequence similarity between the two new
      isolates was 97.5 % but levels of DNA-DNA relatedness between the two were 31.3
      31.8 %. Phylogenetic analysis revealed that the two isolates and [Cytophaga]
      fermentans DSM 9555(T) were affiliated with the family Marinilabiliaceae in the
      class Bacteroidia. The dominant fatty acids of strains MEBiC 07026(T), MEBiC
      08903(T) and [Cytophaga] fermentans DSM 9555(T) were branched-type or
      hydroxylated C15 : 0, but [Cytophaga] fermentans DSM 9555(T) contained a higher
      proportion of anteiso-branched fatty acids. The two new isolates contained a
      markedly higher proportion of monounsaturated fatty acids than other members of
      the family Marinilabiliaceae. The major respiratory quinone of the strains was MK
      7. Strains MEBiC07026(T) and MEBiC08903(T) utilized a wide range of carboxylic
      acids whereas [Cytophaga] fermentans DSM 9555(T) utilized carbohydrates rather
      than carboxylic acids. The DNA G+C content of the novel strains was about 44 mol%
      but that of [Cytophaga] fermentans DSM 9555(T) revealed from the genome sequence
      was 37.6 mol%. Based on evidence from this polyphasic taxonomic study, a novel
      genus, Carboxylicivirga gen. nov., is proposed in the family Marinilabiliaceae
      with two novel species, Carboxylicivirga mesophila sp. nov. with type strain
      MEBiC 07026(T) ( = KCCM 42978(T) = JCM 18290(T)) and Carboxylicivirga taeanensis
      sp. nov. with type strain MEBiC 08903(T) ( = KCCM 43024(T) = JCM 19490(T)).
      Additionally, [Cytophaga] fermentans DSM 9555(T) ( = ATCC 19072(T)) is
      reclassified as Saccharicrinis fermentans gen. nov., comb. nov. 

PMID- 24436063
TI  - Significance of exploiting non-living biomaterials for the biosorption of
      wastewater pollutants.
AB  - Industrial effluents from various sectors have become a matter of major
      environmental concern. The treatment of wastewater in recent year plays a
      significant role in order to remove the pollutants and to safeguard the water
      resource. The conventional wastewater treatment is considered costlier and
      associated with problem of sludge generation. Biosorption methods are considered
      as the potential solution due to their economical efficiency, good adsorption
      capacity and eco-friendliness. In this review, an extensive list of biosorbents
      from algae, bacteria, fungi and agricultural byproducts have been compiled. The
      suitability of biosorbents towards the eradication of heavy metals, textile dyes
      and phenolic compounds were highlighted. It is evident from the literature survey
      of recently published research articles that the biosorbents have demonstrated
      outstanding removal potential towards the wastewater pollutants. Therefore,
      biosorbents from the source of dead microbial and agricultural byproduct can be
      viable alternatives to activated carbon for the wastewater treatment. 

PMID- 24436066
TI  - Aliidiomarina shirensis sp. nov., a halophilic bacterium isolated from Shira Lake
      in Khakasia, southern Siberia, and a proposal to transfer Idiomarina maris to the
      genus Aliidiomarina.
AB  - Strain AIS(T), an aerobic halophilic, Gram-reaction-negative, heterotrophic
      bacterium isolated from the water of Shira Lake in Khakasia, southern Siberia,
      was characterized using a polyphasic approach. Our analysis of the 16S rRNA gene
      sequences showed that 'Aliidiomarina haloalkalitolerans', 'Aliidiomarina
      sanyensis', Idiomarina maris and AIS(T) formed a distinct lineage. The sequence
      similarities between AIS(T) and the type strains of species of the genera
      Idiomarina and Aliidiomarina were 91.6-95.1 % and 94.0-96.9 %, respectively. The
      major isoprenoid quinone of AIS(T) was ubiquinone 8 (Q-8). Predominant cellular
      fatty acids were iso-C17 : 0, iso-C15 : 0 and summed feature 9. The genomic DNA
      G+C content was 45.8 mol%. It is concluded that AIS(T) represents a novel species
      of the genus Aliidiomarina, and the name Aliidiomarina shirensis sp. nov. is
      herein proposed for it. The type strain is AIS(T) ( = JCM 17761(T) = BCRC
      80327(T)). Based on its fatty acid profile and our phylogenetic analysis, we
      propose that Idiomarina maris be transferred to the genus Aliidiomarina. 

PMID- 24436067
TI  - Reclassification of rhizosphere bacteria including strains causing corky root of
      lettuce and proposal of Rhizorhapis suberifaciens gen. nov., comb. nov.,
      Sphingobium mellinum sp. nov., Sphingobium xanthum sp. nov. and Rhizorhabdus
      argentea gen. nov., sp. nov.
AB  - The genus Rhizorhapis gen. nov. (to replace the illegitimate genus name
      Rhizomonas) is proposed for strains of Gram-negative bacteria causing corky root
      of lettuce, a widespread and important lettuce disease worldwide. Only one
      species of the genus Rhizomonas was described, Rhizomonas suberifaciens, which
      was subsequently reclassified as Sphingomonas suberifaciens based on 16S rRNA
      gene sequences and the presence of sphingoglycolipid in the cell envelope.
      However, the genus Sphingomonas is so diverse that further reclassification was
      deemed necessary. Twenty new Rhizorhapis gen. nov.- and Sphingomonas-like
      isolates were obtained from lettuce or sow thistle roots, or from soil using
      lettuce seedlings as bait. These and previously reported isolates were
      characterized in a polyphasic study including 16S rRNA gene sequencing, DNA-DNA
      hybridization, DNA G+C content, whole-cell fatty acid composition, morphology,
      substrate oxidation, temperature and pH sensitivity, and pathogenicity to
      lettuce. The isolates causing lettuce corky root belonged to the genera
      Rhizorhapis gen. nov., Sphingobium, Sphingopyxis and Rhizorhabdus gen. nov. More
      specifically, we propose to reclassify Rhizomonas suberifaciens as Rhizorhapis
      suberifaciens gen. nov., comb. nov. (type strain, CA1(T) = LMG 17323(T) = ATCC
      49355(T)), and also propose the novel species Sphingobium xanthum sp. nov.,
      Sphingobium mellinum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov. with
      the type strains NL9(T) ( = LMG 12560(T) = ATCC 51296(T)), WI4(T) ( = LMG
      11032(T) = ATCC 51292(T)) and SP1(T) ( = LMG 12581(T) = ATCC 51289(T)),
      respectively. Several strains isolated from lettuce roots belonged to the genus
      Sphingomonas, but none of them were pathogenic. 

PMID- 24436068
TI  - Description of Pelistega indica sp. nov., isolated from human gut.
AB  - A Gram-stain-negative, motile, non-spore-forming, coccoid bacterium was isolated
      from a stool sample of a healthy human subject and formed cream colour colonies
      on tryptic soy agar. Almost full-length (1500 bp) small subunit rRNA (16S rRNA)
      gene sequences were generated and a similarity search was conducted by blast. The
      results of the similarity search indicated that the bacterium belongs to the
      class Betaproteobacteria, family Alcaligenaceae. It showed maximum sequence
      similarity (96.5 %) with Pelistega europaea CCUG 39967(T) followed by Advenella
      mimigardefordensis DSM 17166(T) (96.1 %) and Taylorella asinigenitalis LMG
      19572(T) (95.3 %). The DNA G+C content of strain HM-7(T) was 42 mol%. Strain HM
      7(T) contained C14 : 0, C16 : 0, C16 : 0 3-OH and C18 : 0 as the dominant fatty
      acids. Morphological, physiological and biochemical data also indicated that
      strain HM-7(T) represents a member of the genus Pelistega, but at the same time
      distinguished it from Pelistega europaea CCUG 39967(T), the only species of the
      genus with a validly published name. Based on polyphasic characterization we
      conclude that the bacterium represents a novel species of the genus Pelistega and
      propose the name Pelistega indica sp. nov., with strain HM-7(T) ( = MCC 2185(T) =
      DSM 27484(T)) as the type strain of the species. 

PMID- 24436069
TI  - Streptomyces barkulensis sp. nov., isolated from an estuarine lake.
AB  - The taxonomic position of a novel actinomycete, strain RC 1831(T), isolated from
      the sediment of a fish dumping yard at Barkul village near Chilika Lake, Odisha,
      India, was determined by a polyphasic approach. Based on morphological and
      chemotaxonomic characteristics the isolate was determined to belong to the genus
      Streptomyces. The phylogenetic tree based on its nearly complete 16S rRNA gene
      sequence (1428 nt) with representative strains showed that the strain
      consistently falls into a distinct phyletic line together with Streptomyces
      glaucosporus DSM 41689(T) (98.22% similarity) and a subclade consisting of
      Streptomyces atacamensis DSM 42065(T) (98.40%), Streptomyces radiopugnans R97 DSM
      41901(T) (98.27%), Streptomyces fenghuangensis GIMN4.003(T) (98.33 %),
      Streptomyces nanhaiensis DSM 41926(T) (98.13%), Streptomyces megasporus NBRC
      14749(T) (97.37%) and Streptomyces macrosporus NBRC 14748(T) (98.22%). However,
      the levels of DNA-DNA relatedness between strain RC 1831(T) and phylogenetically
      related strains Streptomyces atacamensis DSM 42065(T) (28.75 +/- 3.25%) and
      Streptomyces glaucosporus DSM 41689(T) (15 +/- 2.40%) were significantly lower
      than the 70% threshold value for delineation of genomic species. Furthermore, the
      isolate could be distinguished phenotypically on the basis of physiological,
      morphological and biochemical differences from its closest phylogenetic
      neighbours and other related reference strains. Strain RC 1831(T) is therefore
      considered to represent a novel species of the genus Streptomyces, for which the
      name Streptomyces barkulensis sp. nov. is proposed. The type strain is RC 1831(T)
      ( = JCM 18754(T) = DSM 42082(T)).

PMID- 24436070
TI  - Mucilaginibacter polytrichastri sp. nov., isolated from a moss (Polytrichastrum
      formosum), and emended description of the genus Mucilaginibacter.
AB  - A Gram-staining-negative, rod-shaped, non-spore-forming bacterium, designated
      strain RG4-7(T), was isolated from the moss Polytrichastrum formosum collected
      from Gawalong glacier in Tibet, China, and characterized by using a polyphasic
      taxonomic approach. The predominant fatty acids of strain RG4-7(T) were summed
      feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), iso-C15 : 0 and iso-C17 : 0 3
      OH. The major polar lipids were phosphatidylethanolamine, one unidentified
      aminophospholipid, one unidentified phospholipid, two unidentified aminolipids
      and one unidentified lipid. Strain RG4-7(T) contained MK-7 as the dominant
      menaquinone and the G+C content of its genomic DNA was 39.1 mol%. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain RG4-7(T) was
      affiliated to species of the genus Mucilaginibacter, and its closest relative was
      Mucilaginibacter jinjuensis YC7004(T) (97.0 % sequence similarity). However, the
      DNA-DNA relatedness between this strain and strain RG4-7(T) was only 49.1+/-3.7
      %. Based on phylogenetic inference and phenotypic data, strain RG4-7(T) is
      considered to represent a novel species of the genus Mucilaginibacter, for which
      the name Mucilaginibacter polytrichastri sp. nov. is proposed. The type strain is
      RG4-7(T) ( = CGMCC 1.12493(T) = DSM 26907(T)). An emended description of the
      genus Mucilaginibacter is also proposed. 

PMID- 24436071
TI  - CDK11(p58) kinase activity is required to protect sister chromatid cohesion at
      centromeres in mitosis.
AB  - The cyclin-dependent kinase CDK11(p58) is specifically expressed at G2/M phase.
      CDK11(p58) depletion leads to different cell cycle defects such as mitotic
      arrest, failure in centriole duplication and centrosome maturation, and premature
      sister chromatid separation. We report that upon CDK11 depletion, loss of sister
      chromatid cohesion occurs during mitosis but not during G2 phase. CDK11(p58)
      depletion prevents Bub1 and Shugoshin 1 recruitment but has no effect on the
      dimethylation of histone H3 lysine 4 at centromeres. We also report that a
      construct expressing a kinase dead version of CDK11(p58) fails to prevent CDK11
      depletion-induced sister chromatid separation, showing that CDK11(p58) kinase
      activity is required for protection of sister chromatid cohesion at centromeres
      during mitosis. Thus, CDK11(p58) kinase activity appears to be involved in early
      events in the establishment of the centromere protection machinery. 

PMID- 24436072
TI  - Two separate, but interacting, neural systems for familiarity and novelty
      detection: a dual-route mechanism.
AB  - It has long been assumed that familiarity- and novelty-related processes fall on
      a single continuum drawing on the same cognitive and neural mechanisms. The
      possibility that familiarity and novelty processing involve distinct neural
      networks was explored in a functional magnetic resonance imaging study (fMRI), in
      which familiarity and novelty judgments were made in contexts emphasizing either
      familiarity or novelty decisions. Parametrically modulated BOLD responses to
      familiarity and novelty strength were isolated in two separate, nonoverlapping
      brain networks. The novelty system involved brain regions along the ventral
      visual stream, the hippocampus, and the perirhinal and parahippocampal cortices.
      The familiarity system, on the other hand, involved the dorsomedial thalamic
      nucleus, and regions within the medial prefrontal cortex and the medial and
      lateral parietal cortex. Convergence of the two networks, treating familiarity
      and novelty as a single continuum was only found in a fronto-parietal network.
      Finally, the orbitomedial prefrontal cortex was found to be sensitive to reported
      strength/confidence, irrespective of stimulus' familiarity or novelty. This
      pattern of results suggests a dual-route mechanism supported by the existence of
      two distinct but interacting functional systems for familiarity and novelty.
      Overall, these findings challenge current assumptions regarding the neural
      systems that support the processing of novel and familiar information, and have
      important implications for research into the neural bases of recognition memory.

PMID- 24436073
TI  - Concurrent identity training is not necessary for associative symmetry in
      successive matching.
AB  - Pigeons demonstrate associative symmetry after successive matching training on
      one arbitrary and two identity relations (e.g., Urcuioli, 2008). Here, we tested
      whether identity matching training is necessary for this emergent effect. In
      Experiment 1, one group of pigeons (Dual Oddity) learned hue-form arbitrary
      matching and two oddity relations which shared sample and comparison elements
      with the arbitrary relations. A second (Control) group learned the same hue-form
      matching task and a second (form-hue) arbitrary task which, together with hue
      oddity, shared only the samples with the hue-form relations. On subsequent
      symmetry probe trials, four Dual Oddity pigeons exhibited higher probe-trial
      response rates on the reverse of the positive than negative hue-form baseline
      trials, demonstrating associative symmetry. None of the Control pigeons, on the
      other hand, exhibited associative symmetry. Experiment 2 showed that subsequently
      changing one of the two oddity baseline relations to identity matching in the
      Dual Oddity group yielded antisymmetry in three of five pigeons. These results
      are consistent with predictions derived from Urcuioli's (Urcuioli, 2008) theory
      of pigeons' stimulus class formation and demonstrate that identity training is
      not necessary for associative symmetry to emerge after arbitrary matching
      training in pigeons. 

PMID- 24436075
TI  - Conductor-like screening model for relaxed excited states: Implementation in the
      semiempirical method MSINDO.
AB  - Two approaches to treat solvent polarization and reorientation effects for
      excited states of molecules and surfaces have been implemented in the recently
      developed MSINDO-sCIS method (Gadaczek, Krause, Hintze, Bredow, J. Chem. Theory
      Comput. 2011, 7, 3675). They allow for an efficient calculation of analytical
      energy gradients and hence open the opportunity to investigate fluorescence
      effects or photochemical reactions in solution for large molecules that are
      difficult to treat with high-level methods. Both approaches are based on the
      conductor-like screening model (COSMO) (Klamt and Schuurmann, J. Chem. Soc.,
      Perkin Trans. 1993, 2, 799) in combination with the configuration interaction
      singles (CIS) method (Foresman, Head-Gordon, Pople, and Frisch, J. Phys. Chem.
      1992, 96, 135). The paper gives a brief outline of the theoretical background. As
      a first application, solvent shifts of three well-studied, environment-sensitive
      fluorescent dyes (Kucherak, Didier, Mely, and Klymchenko, J. Phys. Chem. Lett.
      2010, 1, 616) have been calculated and compared with experimental results and
      standard time-dependent density functional theory. A statistical evaluation of
      MSINDO-COSMO-sCIS is provided for a set of 39 molecules suggested recently by
      Jacquemin et al. (Jacquemin, Planchat, Adamo, and Mennucci, J. Chem. Theory
      Comput. 2012, 8, 2359). Calculated vertical and adiabatic excitation energies and
      fluorescence energies are compared to experimental data.

PMID- 24436076
TI  - A general strategy for the catalytic, highly enantio- and diastereoselective
      synthesis of indolizidine-based alkaloids.
AB  - Sixteen indolizidine-based alkaloids (IBAs) that were isolated as poison
      constituents of the skin of frogs were synthesized in a highly flexible and
      stereoselective manner. As a key step, a three-component, organocatalytic, highly
      enantio- and diastereoselective vinylogous Mukaiyama-Mannich reaction was
      employed furnishing optically highly enriched butyrolactams as central
      intermediates on a multigram scale. The attached six-membered ring was
      constructed through cyclization of the pendant enoate moiety onto the pyrrolidine
      ring. The absolute configuration of the bridgehead chiral center and the adjacent
      8-position was established in the initial vinylogous Mannich reaction, whereas
      the 3- and 5-substituents were introduced through organometallic addition at a
      late stage of the synthesis with full stereochemical control from the substrate.
      With this strategy, simple as well as even more complex alkaloids were accessible
      in good overall yields as single stereoisomers. These syntheses also served to
      establish the absolute and relative configuration of those IBAs that had never
      been synthesized before. 

PMID- 24436079
TI  - Outcomes in thread lift for facial rejuvenation: a study performed with happy
      liftTM revitalizing.
AB  - INTRODUCTION: Barbed suture lifting is a minimally invasive surgical technique
      for facial rejuvenation. This study examined the efficacy and associated risks
      with this procedure, using a new synthetic, monofilament suspension thread named
      "Happy LiftTM Revitalizing" (Promoitalia International S.r.l, Naples, Italy).
      METHODS: All the patients had average aging signs and required a lifting of
      modest degree. A total of 37 thread lifts were performed over a 24-month period.
      RESULTS: In the majority of patients (89%), the results obtained were considered
      satisfactory. The incidence of complications was low. Only 6% of the patients had
      slight post-operation asymmetry that was easily corrected. Minor complications
      experienced by patients included small ecchymosis (62%), mild erythema (40%),
      small hemorrhage (25%), mild transitory esthesia (6%) and mild post-operation
      tumefaction (40%). Histopathological and ecographic analyses were performed on
      the treated skin of selected patients, demonstrating that the lifting effect is
      guaranteed and fortified by the cutaneous reaction that appears along the length
      of the thread. CONCLUSION: Thread lift with "Happy LiftTM Revitalizing" is a safe
      procedure associated with minor complications, when performed on cohorts of
      patients requiring a facial lifting of modest degree.

PMID- 24436077
TI  - Discovery of enzyme modulators via high-throughput time-resolved FRET in living
      cells.
AB  - We have used a "two-color" SERCA (sarco/endoplasmic reticulum calcium ATPase)
      biosensor and a unique high-throughput fluorescence lifetime plate reader (FLT
      PR) to develop a high-precision live-cell assay designed to screen for small
      molecules that perturb SERCA structure. A SERCA construct, in which red
      fluorescent protein (RFP) was fused to the N terminus and green fluorescent
      protein (GFP) to an interior loop, was stably expressed in an HEK cell line that
      grows in monolayer or suspension. Fluorescence resonance energy transfer (FRET)
      from GFP to RFP was measured in the FLT-PR, which increases precision 30-fold
      over intensity-based plate readers without sacrificing throughput. FRET was
      highly sensitive to known SERCA modulators. We screened a small chemical library
      and identified 10 compounds that significantly affected two-color SERCA FLT.
      Three of these compounds reproducibly lowered FRET and inhibited SERCA in a dose
      dependent manner. This assay is ready for large-scale HTS campaigns and is
      adaptable to many other targets. 

PMID- 24436080
TI  - The amide III vibrational circular dichroism band as a probe to detect
      conformational preferences of alanine dipeptide in water.
AB  - The conformational preferences of blocked alanine dipeptide (ADP), Ac-Ala-NHMe,
      in aqueous solution were studied using vibrational circular dichroism (VCD)
      together with density functional theory (DFT) calculations. DFT calculations of
      three most representative conformations of ADP surrounded by six explicit water
      molecules immersed in a dielectric continuum have proven high sensitivity of
      amide III VCD band shape that is characteristic for each conformation of the
      peptide backbone. The polyproline II (PII ) and alphaR conformation of ADP are
      associated with a positive VCD band while beta conformation has a negative VCD
      band in amide III region. Knowing this spectral characteristic of each
      conformation allows us to assign the experimental amide III VCD spectrum of ADP.
      Moreover, the amide III region of the VCD spectrum was used to determine the
      relative populations of conformations of ADP in water. Based on the
      interpretation of the amide III region of VCD spectrum we have shown that
      dominant conformation of ADP in water is PII which is stabilized by hydrogen
      bonded water molecules between CO and NH groups on the peptide backbone.

PMID- 24436081
TI  - High-frequency micro-ultrasound: a novel method to assess external urethral
      sphincter function in rats following simulated birth injury.
AB  - AIMS: We evaluated external urethral sphincter (EUS) function using high
      frequency micro-ultrasound (US) in rats that were either uninjured (Control, C)
      or underwent vaginal distension (VD) as a substitute for vaginal birth injury
      induced stress urinary incontinence (SUI). METHODS: Thirteen female nulliparous
      Sprague-Dawley rats of 12 weeks were divided into two groups, either C (n = 6) or
      VD (n = 7). Vaginal balloon distension was performed under pentobarbital
      anesthesia for 4 hours. Five days after the injury, all animals underwent US
      assessment of the urethra during high-rate bladder filling and urine
      leakage/voiding. Urinary leakage, the presence, absence, and pattern of EUS
      bursting during the voiding phase were registered, and pre-determined parameters
      of intercontraction interval (ICI), length of contraction (LOC), and rate of
      contraction (ROC) were registered. RESULTS: Our ultrasound findings consistently
      showed the presence of rhythmic EUS bursting in all of the C rats (6/6), which
      were absent in all VD rats (0/7). The mean of ROC, ICI, and LOC in C group were
      3.02 +/- 0.12 contractions/sec, 471.43 +/- 17.9 msec, and 103.41 +/- 3.28 msec,
      respectively. CONCLUSIONS: Pre-determined parameters of LOC, ICI, and ROC during
      US provide objective and measurable data on EUS function. US showed the total
      disappearance of EUS bursting in the VD group as compared to the C group. These
      results indicate that ultrasound testing may become a valuable non-invasive tool
      in future translational studies to investigate SUI/urethral function in rat
      models.

PMID- 24436082
TI  - Synthesis of highly luminescent and biocompatible CdTe/CdS/ZnS quantum dots using
      microwave irradiation: a comparative study of different ligands.
AB  - We compared the effects of several ligands frequently used in aqueous synthesis,
      including L-cysteine, L-cysteine hydrochloride, N-acetyl-L-cysteine (NAC),
      glutathione and 3-mercaptopropionic acid, for microwave synthesis of CdTe quantum
      dots (QDs) in a sealed vessel with varied temperatures and times, and then
      developed a rapid microwave-assisted protocol for preparing highly luminescent,
      photostable and biocompatible CdTe/CdS/ZnS core-multishell QDs. The effects of
      molecular structures of these ligands on QD synthesis under high temperatures
      were explored. Among these ligands, NAC was found to be the optimal ligand in
      terms of the optical properties of resultant QDs and reaction conditions. The
      emission wavelength of NAC-capped CdTe QDs could reach 700 nm in 5 min by
      controlling the reaction temperature, and the resultant CdTe/CdS/ZnS core
      multishell QDs could achieve the highest quantum yields up to 74% with robust
      photostability. In addition, the effects of temperature, growth time and shell
      precursor ratio on shell growth were examined. Finally, cell culturing indicated
      the low cytotoxicity of CdTe/CdS/ZnS core-multishell QDs as compared to CdTe and
      CdTe/CdS QDs, suggesting their high potential for applications in biomedical
      imaging and diagnostics.

PMID- 24436084
TI  - Subregion-specific decreases in hippocampal serotonin transporter protein
      expression and function associated with endophenotypes of depression.
AB  - Stress influences the development of depression, and depression is associated
      with structural and functional changes in the hippocampus. The current study
      sought to determine whether chronic corticosteroid (CORT) treatment influences
      serotonin transporter (5-HTT) protein expression and function in the CA1, CA3,
      and dentate gyrus (DG) subregions of the hippocampus. Male CD-1 mice were
      subcutaneously injected with CORT at a dose of 20 mg/kg once daily for 3 weeks.
      Behavioral state was assessed using sucrose preference, physical state of the
      coat, forced swimming test, and tail suspension test. We then determine 5-HTT
      protein expression and synaptosomal 5-HT uptake in the CA1, CA3 and DG
      subregions. CORT treatment induced anhedonia and behavioral despair, two core
      endophenotypes of clinical depression; 5-HTT protein expression levels and
      synaptosomal 5-HT uptake were both decreased in a subregion-specific manner, with
      the greatest decrease observed in the DG, a moderate decrease in the CA3, and the
      CA1 showed no apparent change. In addition, a reduction in tissue mass was
      detected in the DG following the CORT treatment. These data indicate that
      subregion-specific decreases in hippocampal 5-HTT protein expression and function
      are associated with endophenotypes of depression.

PMID- 24436083
TI  - Cortical and trabecular bone benefits of mechanical loading are maintained long
      term in mice independent of ovariectomy.
AB  - Skeletal loading enhances cortical and trabecular bone properties. How long these
      benefits last after loading cessation remains an unresolved, clinically relevant
      question. This study investigated long-term maintenance of loading-induced
      cortical and trabecular bone benefits in female C57BL/6 mice and the influence of
      a surgically induced menopause on the maintenance. Sixteen-week-old animals had
      their right tibia extrinsically loaded 3 days/week for 4 weeks using the mouse
      tibial axial compression loading model. Left tibias were not loaded and served as
      internal controls. Animals were subsequently detrained (restricted to cage
      activities) for 0, 4, 8, 26, or 52 weeks, with ovariectomy (OVX) or sham-OVX
      surgery being performed at 0 weeks detraining. Loading increased midshaft tibia
      cortical bone mass, size, and strength, and proximal tibia bone volume fraction.
      The cortical bone mass, area, and thickness benefits of loading were lost by 26
      weeks of detraining because of heightened medullary expansion. However, loading
      induced benefits on bone total area and strength were maintained at each
      detraining time point. Similarly, the benefits of loading on bone volume fraction
      persisted at all detraining time points. The long-term benefits of loading on
      both cortical and trabecular bone were not influenced by a surgically induced
      menopause because there were no interactions between loading and surgery.
      However, OVX had independent effects on cortical bone properties at early (4 and
      8 weeks) detraining time points and trabecular bone properties at all detraining
      time points. These cumulative data indicate loading has long-term benefits on
      cortical bone size and strength (but not mass) and trabecular bone morphology,
      which are not influenced by a surgically induced menopause. This suggests
      skeletal loading associated with physical activity may provide long-term benefits
      by preparing the skeleton to offset both the cortical and trabecular bone changes
      associated with aging and menopause.

PMID- 24436085
TI  - Critical values: has their time arrived for cytopathology?

PMID- 24436086
TI  - Ruthenium(II)/chiral Bronsted acid co-catalyzed enantioselective four-component
      reaction/cascade aza-Michael addition for efficient construction of 1,3,4
      tetrasubstituted tetrahydroisoquinolines.
AB  - An elegant synergistic catalytic system comprising a ruthenium complex with a
      chiral Bronsted acid was developed for a four-component Mannich/cascade aza
      Michael reaction. The ruthenium-associated ammonium ylides successfully trapped
      with in situ generated imines indicates a stepwise process of proton transfer in
      the ruthenium-catalyzed carbenoid N-H insertion reaction. The different
      decomposition abilities of various ruthenium complexes towards diazo compounds
      were well explained by the calculated thermodynamic data. The transformation
      features a mild, rapid, and efficient method for the synthesis of
      enantiomerically pure 1,3,4-tetrasubstituted tetrahydroquinolines bearing a
      quaternary stereogenic carbon center from simple starting precursors in moderate
      yields with high diastereo- and enantioselectivity.

PMID- 24436087
TI  - Clinical features of night eating syndrome among depressed patients.
AB  - OBJECTIVE: The aim of this study was to investigate the frequency and clinical
      features of night eating syndrome (NES) in a sample of patients with depression.
      METHODS: The study sample consisted of 155 depressed outpatients. Socio
      demographic Form, Beck Depression Inventory, Beck Anxiety Inventory, Maudsley
      Obsessive-Compulsive Inventory, Pittsburgh Sleep Quality Index (PSQI) and Night
      Eating Questionnaire were utilised for data collection. RESULTS: Night eating
      syndrome was identified in 21.3% of the patients. Comparisons between NES and non
      NES patients revealed significant differences in BMI, smoking status, Beck
      Depression Inventory, Beck Anxiety Inventory, rumination and PSQI sub-scores for
      sleep quality, latency, disturbances and daytime dysfunction. In our sample, the
      predictors of NES were BMI, smoking and the subject's score on the PSQI sleep
      disturbances subscale. CONCLUSIONS: Night eating syndrome is negatively
      associated with sleep, severity of anxiety and depression. Our findings suggest
      that there is a complex relation between NES and depression, and it is
      recommended that depressed patients be evaluated for NES.

PMID- 24436088
TI  - Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea
      pig prostate gland.
AB  - AIMS: To examine the effects of the alpha1A -adrenoceptor antagonist, tamsulosin,
      on spontaneous contractile and electrical activity in the guinea-pig prostate
      gland. METHODS: The effects of tamsulosin (0.1 and 0.3 nM) were investigated in
      adult and ageing male guinea pig prostate glands using conventional tension
      recording and electrophysiological intracellular microelectrode recording
      techniques. RESULTS: Tamsulosin reduced spontaneous activity, and had different
      age-dependent effects on adult and ageing guinea pigs at different
      concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of
      spontaneous contractile and electrical activity in ageing guinea pigs in
      comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a
      significantly greater reduction of spontaneous contractile and electrical
      activity in adult guinea pigs in comparison to ageing guinea pigs. CONCLUSIONS:
      This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal
      contractility and the underlying spontaneous electrical activity; tamsulosin does
      not block spontaneous activity. This reduction in spontaneous activity suggests
      that downstream cellular mechanisms underlying smooth muscle tone are being
      targeted, and these may represent novel therapeutic targets to better treat
      benign prostatic hyperplasia.

PMID- 24436089
TI  - Electron localizability indicators from spinor wavefunctions.
AB  - For the fully relativistic 4-component many-electron wavefunction six flavors of
      electron localizability indicators (ELI) have been proposed. Their counterparts,
      suitable for the application to the 2-component wavefunctions, have been also
      derived. Six proposed indicators have been tested on Ar and Rn atoms and one of
      them, the ELI-D for spatially antisymmetrized electron pairs, has been found to
      reveal atomic shell structures at quantitative level. Shell structures of all the
      atoms of periods 4-7 of the periodic table have been obtained using this
      indicator and compared with these obtained from the nonrelativistic limit
      calculations as well as from scalar-relativistic (zero-order regular
      approximation) calculations.

PMID- 24436090
TI  - Responding by exclusion in temporal discrimination tasks.
AB  - Responding by exclusion, one of the most robust phenomena in Experimental
      Psychology, describes a particular form of responding observed in symbolic,
      matching-to-sample tasks. Given two comparison stimuli, one experimentally
      defined and one experimentally undefined, the participant prefers the undefined
      comparison following an undefined sample. The goal of the present study was to
      determine whether responding by exclusion could be obtained using samples that
      varied along a single dimension. Using a double temporal bisection task, 10
      university students learned to choose visual comparisons (colored circles) based
      on the duration of a tone. In tests of exclusion, sample stimuli with new
      durations were followed by comparison sets that included one previously trained,
      defined comparison (colored circle) and one previously untrained, undefined
      comparison (geometric shape). Participants preferred the defined comparisons
      following the defined samples and the undefined comparisons following the
      undefined samples, the choice pattern typical of responding by exclusion. The use
      of samples varying along a single dimension allows us to study the interaction
      between stimulus generalization gradients and exclusion in the control of
      conditional responding. 

PMID- 24436092
TI  - Cerebrospinal fluid lysosomal enzymes and alpha-synuclein in Parkinson's disease.
AB  - To assess the discriminating power of multiple cerebrospinal fluid (CSF)
      biomarkers for Parkinson's disease (PD), we measured several proteins playing an
      important role in the disease pathogenesis. The activities of beta
      glucocerebrosidase and other lysosomal enzymes, together with total and
      oligomeric alpha-synuclein, and total and phosphorylated tau, were thus assessed
      in CSF of 71 PD patients and compared to 45 neurological controls. Activities of
      beta-glucocerebrosidase, beta-mannosidase, beta-hexosaminidase, and beta
      galactosidase were measured with established enzymatic assays, while alpha
      synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD
      patients (n = 44) was also screened for mutations in the beta-glucocerebrosidase
      encoding gene (GBA1). In the PD group, beta-glucocerebrosidase activity was
      reduced (P < 0.05) and patients at earlier stages showed lower enzymatic activity
      (P < 0.05); conversely, beta-hexosaminidase activity was significantly increased
      (P < 0.05). Eight PD patients (18%) presented GBA1 sequence variations; 3 of them
      were heterozygous for the N370S mutation. Levels of total alpha-synuclein were
      significantly reduced (P < 0.05) in PD, in contrast to increased levels of alpha
      synuclein oligomers, with a higher oligomeric/total alpha-synuclein ratio in PD
      patients when compared with controls (P < 0.001). A combination of beta
      glucocerebrosidase activity, oligomeric/total alpha-synuclein ratio, and age gave
      the best performance in discriminating PD from neurological controls (sensitivity
      82%; specificity 71%, area under the receiver operating characteristic curve =
      0.87). These results demonstrate the possibility of detecting lysosomal
      dysfunction in CSF and further support the need to combine different biomarkers
      for improving the diagnostic accuracy of PD.

PMID- 24436093
TI  - Resting arterial oxygen saturation and breathing frequency as predictors for
      acute mountain sickness development: a prospective cohort study.
AB  - INTRODUCTION: The study evaluated the predictive value of arterial oxygen
      saturation (SaO2) after 30-min hypoxic exposure on subsequent development of
      acute mountain sickness (AMS) and tested if additional resting cardio-respiratory
      measurements improve AMS prognosis. METHODS: Fifty-five persons were exposed to a
      simulated altitude of 4,500 m (normobaric hypoxia, FiO2 = 12.5%). Cardio
      respiratory parameters, SaO2, blood lactate, and blood pressure were measured
      after 30 min of exposure. AMS symptoms were recorded after 3, 6, 9, and 12 h
      (Lake-Louise Score). Three models, based on previously published regression
      equations for altitude-dependent SaO2 values of AMS-susceptible (SaO2-suscept =
      98.34 - 2.72 * alt - 0.35 * alt(2)) and AMS-resistant (SaO2-resist = 96.51 + 0.68
      * alt - 0.80 * alt(2)) persons, were applied to predict AMS. Additionally,
      multivariate logistic regression analyses were conducted to test if additional
      resting measurements improve AMS prediction. RESULTS: The three models correctly
      predicted AMS development in 62%, 67%, and 69% of the cases. No model showed
      combined sensitivity and specificity >80%. Sequential logistic regression
      revealed that the inclusion of tidal volume or breathing frequency in addition to
      SaO2 improved overall AMS prediction, resulting in 78% and 80% correct AMS
      prediction, respectively. CONCLUSION: Non-invasive measurements of SaO2 after 30
      min hypoxic exposure are easy to perform and have the potential to detect AMS
      susceptible individuals with a sufficient sensitivity. The additional
      determination of breathing frequency can improve success in AMS prediction.

PMID- 24436095
TI  - Pontine watershed infarction.

PMID- 24436094
TI  - Urinary concentration of 8-isoprostane as marker of severity of pediatric OSAS.
AB  - BACKGROUND: F2-isoprostanes are considered to be a reliable standard biomarker of
      oxidative stress in vivo because they are not influenced by the intake of lipids
      in the diet, and they are chemically stable molecules and easily detected. This
      study aimed to test the hypothesis that 8-isoprostane level is a useful marker to
      valuate the severity of pediatric obstructive sleep apnea (OSA). METHODS: Sixty
      five children with sleep-disordered breathing (SDB) (mean age 5.9+/-2.0 years;
      63.1% males) were recruited. The urine sample for the measurement of 8
      isoprostane was collected the morning after the polysomnographic recording.
      Children were divided into two groups according to their apnea-hypopnea index
      (AHI). RESULTS: Urinary 8-isoprostane levels positively correlated with the sleep
      clinical record score (r=0.38, p=0.002) and AHI (r=0.24, p=0.05) and negatively
      correlated with age (r=-0.36, p=0.003) and body surface area (r=-0.38, p=0.002).
      Urinary 8-isoprostane levels were significantly higher in the group with AHI of
      >=5 events (ev)/h than in the group with AHI of <5 ev/h (p<0.01). CONCLUSIONS:
      Urinary 8-isoprostane may be used as a specific inflammatory marker to predict
      the severity of OSA; this method has the advantage of being noninvasive and easy
      to use in both compliant and noncompliant children.

PMID- 24436096
TI  - S100A9 has a protective role in inflammation-induced skin carcinogenesis.
AB  - The S100A8/A9 heterodimer is expressed by myeloid cells where its function has
      been extensively investigated. Immune cell S100A8/A9 promotes proinflammatory
      effects, and its absence is often associated with lack of leukocyte recruitment
      resulting in protection in terms of disease progression. S100A8/A9 is also
      expressed by certain epithelia, either constitutively as in mucosal epithelia or
      following stimulation as in skin keratinocytes. The role of the heterodimer in
      this context has not been as frequently explored. In this study, the incidence of
      skin papillomas induced by 7,12-dimethylbenz(a)anthracene (DMBA)/12-O
      tetradecanoylphorbol-13-acetate (TPA) in S100a9(-/-) mice has been investigated.
      Unlike the immune disorders and certain models of cancer, absence of S100A8/A9
      caused an increased incidence in skin of papillomas and, subsequently, squamous
      cell carcinomas. Although associated in S100a9(-/-) mice with increased
      recruitment of neutrophils and T cells, a bone marrow chimera experiment revealed
      the major defect to be primarily due to the absence of S100A8/A9 in the skin
      keratinocytes. S100a9(-/-) skin displayed enhanced Ki-67 expression over the time
      period of appearance of the papillomas suggesting an effect of S100A8/A9 in
      regulating proliferation in the epidermal layer. Thus, despite immune cell
      recruitment in S100a9(-/-) mouse skin that might have been predicted to promote
      tumor growth, it was the absence of S100A8/A9 in skin keratinocytes that
      dominated in terms of papilloma formation. The study highlights the importance of
      the S100A8/A9-expressing skin epidermal layer in controlling skin tumor formation
      and suggests that the influence of the heterodimer is dependent on the tissue
      context in which it is expressed. 

PMID- 24436098
TI  - A survival guide for psychiatric residency training directors.
AB  - This paper catalogues the inevitable problems that beset training directors and
      describes coping strategies designed to improve the likelihood of the training
      director's survival and the quality of his or her life. The difficulties of the
      job include picking residents, struggling to assure that the faculty provides
      decent teaching programs, contending with repetitive bureaucratic details, being
      overloaded by numerous tasks, and warily watching as residents who somehow
      squeaked through the program are sent off on their own. Offsetting the hassles
      are the exciting jobs of picking residents, guiding the faculty in setting up
      teaching programs, keeping a complicated program running, mastering numerous
      challenges, and watching with satisfaction as new, competent psychiatrists
      graduate. 

PMID- 24436097
TI  - Is representativeness the right question?

PMID- 24436099
TI  - Interrater reliability in evaluating trainee interviewing skills.
AB  - The reliability of the evaluative judgments by psychiatric faculty of physician
      trainee interviewing skills was studied. Three methods were included: global
      rating scales, data checklists, and a time-allotment form. Data were obtained
      during a training workshop for psychiatric instructors in the U.S. The authors
      found low interrater reliability with all three methods. The study findings were
      replicated at a second workshop with Canadian faculty. The authors outline some
      recommended modifications of observational systems that may help improve both the
      accuracy and reliability of ratings of trainee interviewing skills. The use of
      more accurate quantitative techniques is briefly reviewed. 

PMID- 24436100
TI  - AIDS as a paradigm of human behavior in disease : impact and implications of a
      course.
AB  - A new required psychiatry course for first-year medical students linked the
      urgent need for acquired immune deficiency syndrome (AIDS) education with the
      traditional goal of teaching the biopsychosocial model of illness. The course,
      "Human Behavior in Disease: AIDS as Paradigm," used HIV/AIDS to demonstrate
      principles of all life-threatening diseases. Formal evaluations of the course's
      impact indicated that it significantly reduced students' prejudices and increased
      positive attitudes regarding AIDS patients. The students' ratings of the course
      indicated that the AIDS paradigm was understood and valued. Our experience
      suggests that preclinical psychiatry courses can play an important role in the
      medical educational response to AIDS, while, at the same time, achieving their
      traditional curricular goals. 

PMID- 24436101
TI  - An Assessment of Psychiatric Residents' Knowledge and Attitudes Regarding ECT.
AB  - Graduating psychiatric residents in the Philadelphia area were surveyed about
      their attitudes, training experiences, and knowledge regarding electroconvulsive
      therapy (ECT). Twenty-nine residents were interviewed. Although the majority of
      respondents expressed positive attitudes about the use of ECT, only two (7%)
      expressed confidence in their own ability to perform the treatment without
      supervision. The residents' general attitudes regarding ECT as a therapeutic
      modality were consistent with those of previous surveys of practicing
      psychiatrists. The level of knowledge of the residents interviewed was not
      related to reported didactic or practical experience. Significant gaps in
      training were noted. The need for more thorough, standardized training in ECT is
      discussed. 

PMID- 24436102
TI  - From the benches to the trenches : training residents to provide emergency
      outreach services-a public/academic project.
AB  - The Charleston Area Mental Health Center and the Department of Psychiatry and
      Behavioral Sciences at the Medical University of South Carolina have collaborated
      to form a comprehensive emergency service with mobile capacity. The service is
      staffed by an interdisciplinary team of professionals from public and academic
      psychiatry. Psychiatric residents are fully integrated into the service. A
      description of the program demonstrates how such liaisons can promote improved
      access to high-quality services, while enriching the training of psychiatrists
      through outreach experiences. 

PMID- 24436103
TI  - Teaching short-term psychotherapy with blind role playing.
AB  - This report describes the use of blind role playing to introduce the theory and
      techniques of the short-term psychotherapies in a combined "laboratory" and
      lecture course. "Therapist" and "patient" (but not instructor) are blind to each
      other's governing assumptions about therapy, yet must respond creatively to each
      other based on the algorithms of the "script" and on real-life experience as both
      doctor and patient. 

PMID- 24436104
TI  - The inpatient database as a technique to prevent junior faculty burnout.
AB  - Junior faculty members beginning their careers in academic psychiatry are
      frequently assigned major clinical duties as directors of busy inpatient
      psychiatry units, leaving them little time or energy for research. The turnover
      in these positions is high and job dissatisfaction higher. This paper describes
      an inpatient database developed and used by the author as a clinical research
      tool to explore interesting questions about inpatient psychiatry and better
      integrate the academic and clinical service aspects of his junior faculty role. 

PMID- 24436106
TI  - Protease-activated receptor-1 drives pancreatic cancer progression and
      chemoresistance.
AB  - Protease activated receptor (PAR)-1 expression in tumor cells is associated with
      disease progression and overall survival in a variety of cancers of epithelial
      origin; however, the importance of PAR-1 in the tumor microenvironment remains
      unexplored. Utilizing an orthotopic pancreatic cancer model in which tumor cells
      are PAR-1 positive whereas stromal cells are PAR-1 negative, we show that PAR-1
      expression in the microenvironment drives progression and induces chemoresistance
      of pancreatic cancer. PAR-1 enhances monocyte recruitment into the tumor
      microenvironment by regulating monocyte migration and fibroblast dependent
      chemokine production thereby inducing chemoresistance. Overall, our data identify
      a novel role of PAR-1 in the pancreatic tumor microenvironment and suggest that
      PAR-1 may be an attractive target to reduce drug resistance in pancreatic cancer.

PMID- 24436105
TI  - What is the role for biomarkers for lower urinary tract disorders? ICI-RS 2013.
AB  - AIMS: A biomarker is an entity that measures a normal or pathological process, or
      the response to an intervention. A biomarker must measure exclusively and be
      sufficiently sensitive to the process of interest. Alternatively, a biomarker may
      give clues regarding the underlying pathology of the condition and be a useful
      research or specialist tool. If a biomarker is to be of practical benefit then it
      must also be economical and practical to use. This article will consider chemical
      moieties as biomarkers, although in principle physical markers (e.g., bladder
      wall thickness) could also be defined as such. RESULTS AND CONCLUSIONS: The
      validation of a biomarker for detrusor overactivity (DO) must appreciate the fact
      that the condition is likely to multifactorial and thus no single entity may be
      sufficiently selective and sensitive. However, more specific conditions, such as
      bladder pain associated with DO, may make the biomarker search easier. Several
      prospective agents including antiproliferative factor (APF) and epidermal growth
      factors (EGF) are discussed. Several urinary biomarkers, including neurotrophins
      (NGF, BDNF) and cytokines, and a serum marker, C-reactive protein, are considered
      as reaching the above criteria. All suffer from relatively poor lack of
      discrimination, as they all change in response to other, often inflammatory,
      conditions; BDNF may offer the highest expectations. Urinary ATP has also been
      proposed as a DO/OAB biomarker but requires further evaluation. Finally genetic
      markers offer potential to understand more about the pathophysiology of DO/OAB.
      The increasing availability of genome-wide association studies and micro-RNA
      assays offer genetic markers as a new generation of biomarkers. Neurourol.
      Urodynam. 33:602-605, 2014. (c) 2014 Wiley Periodicals, Inc.

PMID- 24436107
TI  - Tl(+) showed negligible interaction with inner membrane sulfhydryl groups of rat
      liver mitochondria, but formed complexes with matrix proteins.
AB  - The effects of Tl(+) on protein sulfhydryl (SH) groups, swelling, and respiration
      of rat liver mitochondria (RLM) were studied in a medium containing TlNO3 and
      sucrose, or TlNO3 and KNO3 as well as glutamate plus malate, or succinate plus
      rotenone. Detected with Ellman's reagent, an increase in the content of the SH
      groups was found in the inner membrane fraction, and a simultaneous decline was
      found in the content of the matrix-soluble fraction for RLM, incubated and frozen
      in 25-75 mM TlNO3 . This increase was greater in the medium containing KNO3
      regardless of the presence of Ca(2+) . It was eliminated completely for RLM
      injected in the medium containing TlNO3 and then washed and frozen in the medium
      containing KNO3 . Calcium-loaded RLM showed increased swelling and decreased
      respiration. These results suggest that a ligand interaction of Tl(+) with
      protein SH groups, regardless of the presence of calcium, may underlie the
      mechanism of thallium toxicity. 

PMID- 24436108
TI  - Characterizing context-dependent differential firing activity in the hippocampus
      and entorhinal cortex.
AB  - The rat hippocampus and entorhinal cortex have been shown to possess neurons with
      place fields that modulate their firing properties under different behavioral
      contexts. Such context-dependent changes in neural activity are commonly studied
      through electrophysiological experiments in which a rat performs a continuous
      spatial alternation task on a T-maze. Previous research has analyzed context
      based differential firing during this task by describing differences in the mean
      firing activity between left-turn and right-turn experimental trials. In this
      article, we develop qualitative and quantitative methods to characterize and
      compare changes in trial-to-trial firing rate variability for sets of
      experimental contexts. We apply these methods to cells in the CA1 region of
      hippocampus and in the dorsocaudal medial entorhinal cortex (dcMEC),
      characterizing the context-dependent differences in spiking activity during
      spatial alternation. We identify a subset of cells with context-dependent changes
      in firing rate variability. Additionally, we show that dcMEC populations encode
      turn direction uniformly throughout the T-maze stem, whereas CA1 populations
      encode context at major waypoints in the spatial trajectory. Our results suggest
      scenarios in which individual cells that sparsely provide information on turn
      direction might combine in the aggregate to produce a robust population encoding.

PMID- 24436109
TI  - Microscopic analysis of the localization of two chlorin-based photosensitizers in
      OSC19 tumors in the mouse oral cavity.
AB  - BACKGROUND AND OBJECTIVE: The effect of photodynamic therapy (PDT) is dependent
      on the localization of photosensitizer in the treatment volume at the time of
      illumination. Investigation of photosensitizer pharmacokinetics in and around the
      treatment volume aids in determining the optimal drug light interval for PDT.
      MATERIALS AND METHODS: In this paper we have investigated the distribution of the
      photosensitizers chlorin e6 and Bremachlorin in the oral squamous cell carcinoma
      cell-line OSC19-Luc-Gfp in a tongue tumor, tumor boundary, invasive tumor
      boundary, and normal tongue tissue by the use of confocal microscopy of frozen
      sections. Tongues were harvested at t = [3, 4.5, 6, 24, 48] hours after
      injection. RESULTS: Both photosensitizers showed a decreasing fluorescence with
      increasing incubation time, and at all time points higher fluorescence was
      measured in tumor boundary than in tumor itself. For short incubation times, a
      higher fluorescence intensity was observed in the invasive tumor border and
      normal tissue compared to tumor tissue. Bremachlorin showed a small increase in
      tumor to normal ratio at 24 and 48 hours incubation time. Ce6 was undetectable at
      48 hours. We did not find a correlation between photosensitizer localization and
      the presence of vasculature. CONCLUSION: The modest tumor/tumor boundary to
      normal selectivity of between 1.2 and 2.5 exhibited by Bremachlorin 24 and 48
      hours after administration may allow selective targeting of tongue tumors.
      Further studies investigating the relationship between Bremachlorin concentration
      and therapeutic efficacy PDT with long incubation times are warranted.

PMID- 24436110
TI  - Atypical cytologic diagnostic category in EUS-FNA of the pancreas: follow-up,
      outcomes, and predictive models.
AB  - BACKGROUND: The objective of this study was to assess how atypical diagnostic
      category (ADC) is followed up, its outcomes, and the predictors that are
      associated with subsequent diagnosis of neoplasm/malignancy. METHODS: We reviewed
      pancreatic endoscopic ultrasound fine-needle aspiration (EUS-FNA) with ADC and
      compared the rate of detection of neoplasms after a repeat FNA, a
      biopsy/resection, or a clinical follow-up following ADC. Logistic regression was
      used to determine the factors associated with the diagnosis of a neoplastic or a
      malignant lesion following ADC. Predictive probability for each case was
      calculated on the basis of the significant predictors, and whether it improved
      diagnostic performance was assessed. RESULTS: Of 3832 cases that received
      pancreatic EUS-FNAs, 187 (4.9%) were ADC. A total of 93 neoplasms (55%),
      including 61 carcinomas (36%), were detected after an atypical cytologic
      diagnosis. Similar rates of detecting neoplasms were observed after repeat FNA or
      biopsy/resection but higher than after clinical follow-up. The presence of a
      mass, history of alcohol use, and absence of a history of pancreatitis were
      significant predictors of a higher rate of diagnosis of neoplasm. Weight loss and
      bile flow obstruction were more likely to be associated with higher rates of
      carcinoma. Predictive probability demonstrated a wide range of risk and changed
      the ambiguous diagnosis to informative in 30% of cases. CONCLUSIONS: ADC of
      pancreas is associated with a high risk of benign and malignant neoplasms
      regardless of the method of follow-up. The presences of a mass, alcohol use, and
      absence of a history of pancreatitis are significant predictors of a diagnosis of
      neoplasm, whereas weight loss and bile duct obstruction are significant
      predictors of ductal carcinoma following an ADC.

PMID- 24436111
TI  - Cognitive impairment in rapid-onset dystonia-parkinsonism.
AB  - Rapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3
      gene. This observational study sought to determine if cognitive performance is
      decreased in patients with RDP compared with mutation-negative controls. We
      studied 22 familial RDP patients, 3 non-motor-manifesting mutation-positive
      family members, 29 mutation-negative family member controls in 9 families, and 4
      unrelated RDP patients, totaling 58 individuals. We administered a movement
      disorder assessment, including the Burke-Fahn-Marsden Dystonia Rating Scale
      (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive
      battery of memory and learning, psychomotor speed, attention, and executive
      function. The cognitive battery was designed to evaluate a wide range of
      functions; recognition memory instruments were selected to be relatively pure
      measures of delayed memory, devoid of significant motor or vocal production
      limitations. Comparisons of standardized cognitive scores were assessed both with
      and without controlling for psychomotor speed and similarly for severity of
      depressive symptoms. A majority of RDP patients had onset of motor symptoms by
      age 25 and had initial symptom presentation in the upper body (face, mouth, or
      arm). Among patients, the BFMDRS (mean +/- SD, 52.1 +/- 29.5) and UPDRS motor
      subscore (29.8 +/- 12.7) confirmed dystonia-parkinsonism. The affected RDP
      patients performed more poorly, on average, than mutation-negative controls for
      all memory and learning, psychomotor speed, attention, and executive function
      scores (all P <= 0.01). These differences persisted after controlling for
      psychomotor speed and severity of depressive symptoms. Impaired cognitive
      function may be a manifestation of ATP1A3 mutation and RDP.

PMID- 24436113
TI  - Pausing as an operant: choice and discriminated responding.
AB  - The effects of intermittent schedules of reinforcement for pausing were evaluated
      in two experiments. In Experiment 1, across a series of conditions, a variable
      interval (VI) baseline schedule, in which pigeons' key pecks produced food,
      alternated with conditions in which food was delivered according to a concurrent
      VI (for key pecking) tandem variable-time differential-reinforcement-of-other
      behavior (DRO) 5-s schedule. Time spent pausing within a session was proportional
      to the reinforcement rates associated with the tandem schedule. To examine the
      control of pausing by antecedent events, Experiment 2 arranged a multiple
      schedule in which pecking and pausing in either component were maintained
      according to concurrent schedules like those used in the first experiment. The
      availability of reinforcement for pausing was signaled in one component while
      signals uncorrelated with reinforcement were presented in the other. Signaled
      reinforcement for pausing, relative to the presentation of uncorrelated signals,
      decreased time spent pausing, a finding consistent with existing research on the
      effects of signaled VI reinforcement for key pecking in pigeons. The results of
      the two experiments show that pausing functions as an operant in much the same
      way that discrete responses, like key pecks, do, and that pausing and other
      operants are similarly affected by both antecedent and consequent events. 

PMID- 24436112
TI  - Manganese-enhanced MRI (MEMRI) via topical loading of Mn(2+) significantly
      impairs mouse visual acuity: a comparison with intravitreal injection.
AB  - Manganese-enhanced MRI (MEMRI) with topical loading of MnCl2 provides optic nerve
      enhancement comparable to that seen by intravitreal injection. However, the
      impact of this novel and non-invasive Mn(2+) loading method on visual function
      requires further assessments. The objective of this study is to determine the
      optimal topical Mn(2+) loading dosage for MEMRI and to assess visual function
      after MnCl2 loading. Intravitreal administration was performed to compare the two
      approaches of MnCl2 loading. Twenty-four hours after topical loading of 0, 0.5,
      0.75, and 1 M MnCl2 , T1 -weighted, T2-weighted, diffusion tensor imaging and
      visual acuity (VA) assessments were performed to determine the best topical
      loading dosage for MEMRI measurements and to assess the integrity of retinas and
      optic nerves. Mice were perfusion fixed immediately after in vivo experiments for
      hematoxylin and eosin and immunohistochemistry staining. Topical loading of 1 M
      MnCl2 damaged the retinal photoreceptor layer with no detectable damage to retina
      ganglion cell layers or prechiasmatic optic nerves. For the topical loading, 0.75
      M MnCl2 was required to see sufficient enhancement of the optic nerve. At this
      concentration the visual function was significantly affected, followed by a slow
      recovery. Intravitreal injection (0.25 MUL of 0.2 M MnCl2 ) slightly affected VA,
      with full recovery a day later. To conclude, intravitreal MnCl2 injection
      provides more reproducible results with less adverse side-effects than topical
      loading.

PMID- 24436114
TI  - Long-term outcome of intravesical oxybutynin in children with detrusor-sphincter
      dyssynergia: with special reference to age-dependent parameters.
AB  - AIMS: Intravesical instillation of oxybutynin is an accepted and effective
      treatment in children with neuropathic bladder-sphincter dysfunction, when oral
      oxybutynin results in inadequate suppression of detrusor overactivity or
      intolerable side effects. However, as yet no data are available on long-term use
      and outcome. METHODS: A patient cohort with detrusor-sphincter dyssynergia that
      started oral oxybutynin between 1995 and 1997 was re-evaluated 15 +/- 1 years
      after the switch from oral to intravesical (n = 10), with urodynamic
      investigations, renal ultrasounds, DMSA-scintigraphy, (51)Cr-EDTA-clearance, and
      validated questionnaires on incontinence and quality of life. RESULTS: At follow
      up, cystometric bladder capacity (CBC) had increased to the 25-50% percentiles
      for age, from the 5% percentile; mean end-filling pressure, 24.5 +/- 14.4 cm H2O,
      had returned to the safe zone; bladder compliance expressed as a fraction of
      normal compliance for age (Wahl units) showed a statistically significant
      increase. At follow-up, the prevalence of renal scars was 30% (95% CI: 6-65%).
      Kidney lengths correlated with scarring at DMSA-scintigraphy, (51)Cr-EDTA
      clearance did not. In 2 years of oral oxybutynin we documented 10 pyelonephritic
      episodes, in 15 years of intravesical oxybutynin only three. Urinary continence
      was reported as satisfying, its impact on quality of life as acceptable.
      CONCLUSION: Percentile charts for cystometric bladder capacity and individual
      kidney lengths, age-dependent parameters, were invaluable in estimating long-term
      outcome, and the same goes for bladder compliance in Wahl units. We can conclude
      that intravesical oxybutynin provided more than adequate suppression of detrusor
      activity, without side effects, over a period of 15 years.

PMID- 24436115
TI  - No gains in efficacy observed by adding gemcitabine to adjuvant therapy for lymph
      node-positive breast cancer.

PMID- 24436116
TI  - Fecal occult blood testing remains a valuable screening tool.

PMID- 24436118
TI  - Behavioral anxiolysis without reduction of hippocampal theta frequency after
      histamine application in the lateral septum of rats.
AB  - Hippocampal theta activity is linked to various processes, including locomotion,
      learning and memory, and defense and affect (i.e., fear and anxiety).
      Interestingly, all classes of clinically effective anxiolytics, as well as
      experimental compounds that decrease anxiety in pre-clinical animal models of
      anxiety, reduce the frequency of hippocampal theta activity elicited by
      stimulation of the reticular formation in freely behaving or anesthetized
      animals. In the present experiments, we found that bilateral histamine infusions
      (0.5 ug/hemisphere) into the lateral septum (LS) of rats decreased anxiety-like
      responses in two models of anxiety, the elevated plus maze and novelty-induced
      suppression of feeding test. Surprisingly, these same infusions significantly
      increased hippocampal theta frequency elicited by reticular stimulation in
      urethane-anesthetized rats. In contrast to these findings, additional experiments
      showed that the clinically effective anxiolytic buspirone (40 mg/kg, i.p.)
      reduced theta frequency, confirming previous observations. Taken together, the
      dissociation of behavioral anxiolysis and theta frequency reduction noted here
      suggest that hippocampal theta frequency is not a direct index of anxiety levels
      in rodents. Further, the mechanisms underlying the behavioral and physiological
      effects elicited by histamine in the LS require further study.

PMID- 24436119
TI  - Factors associated with elder mistreatment in rural Tamil Nadu, India: a cross
      sectional survey.
AB  - BACKGROUND: There is limited evidence for the multifactorial aetiology of elder
      mistreatment. The goal of this study is to investigate the factors associated
      with the mistreatment of older adults living in rural Tamil Nadu, India. METHOD:
      A cross-sectional household survey was conducted in a sub-district of rural Tamil
      Nadu by using a standard questionnaire. Face to face interviews were conducted
      with 902 older adults aged 61 years and older. The relation between the
      characteristics of older adults, family members and family environments with
      reported mistreatment was examined by univariate and multivariate logistic
      regression analyses. RESULTS: The multivariate results reveal that elder
      mistreatment is related to several factors associated with the perpetrator and
      the family environment. Perpetrator factors include middle age, a tertiary
      education (protective), alcohol consumption and the mistreatment of other family
      members. Family environment factors include family stress and low cohesion. Among
      the factors related to older adults, only physical abuse of family members was
      associated with exposure to mistreatment. CONCLUSION: The characteristics of
      older adults, family members and family environment are potent predictors of
      elder mistreatment. Multi-dynamic interventions should target dysfunctional
      families displaying alcohol use, relationship conflicts, low cohesion and the
      presence of some form of family violence.

PMID- 24436117
TI  - Gene delivery in malignant B cells using the combination of lentiviruses
      conjugated to anti-transferrin receptor antibodies and an immunoglobulin
      promoter.
AB  - BACKGROUND: We previously developed an antibody-avidin fusion protein (ch128.1Av)
      specific for the human transferrin receptor 1 (TfR1; CD71) to be used as a
      delivery vector for cancer therapy and showed that ch128.1Av delivers the
      biotinylated plant toxin saporin-6 into malignant B cells. However, as a result
      of widespread expression of TfR1, delivery of the toxin to normal cells is a
      concern. Therefore, we explored the potential of a dual targeted lentiviral
      mediated gene therapy strategy to restrict gene expression to malignant B cells.
      Targeting occurs through the use of ch128.1Av or its parental antibody without
      avidin (ch128.1) and through transcriptional regulation using an immunoglobulin
      promoter. METHODS: Flow cytometry was used to detect the expression of enhanced
      green fluorescent protein (EGFP) in a panel of cell lines. Cell viability after
      specific delivery of the therapeutic gene FCU1, a chimeric enzyme consisting of
      cytosine deaminase genetically fused to uracil phosphoribosyltransferse that
      converts the 5-fluorocytosine (5-FC) prodrug into toxic metabolites, was
      monitored using the MTS or WST-1 viability assay. RESULTS: We found that EGFP was
      specifically expressed in a panel of human malignant B-cell lines, but not in
      human malignant T-cell lines. EGFP expression was observed in all cell lines when
      a ubiquitous promoter was used. Furthermore, we show the decrease of cell
      viability in malignant plasma cells in the presence of 5-FC and the FCU1 gene.
      CONCLUSIONS: The present study demonstrates that gene expression can be
      restricted to malignant B cells and suggests that this dual targeted gene therapy
      strategy may help to circumvent the potential side effects of certain TfR1
      targeted protein delivery approaches.

PMID- 24436120
TI  - Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell
      carcinomas and correlation with patient outcome.
AB  - CDKN2A (p16) disruption is reported as a frequent event in head and neck squamous
      cell carcinomas that confers poor prognosis. We investigated the frequency of
      different potential mechanisms of CDKN2A inactivation in oral tongue squamous
      cell carcinomas (OTSCC) and their impact on patient outcome. From a cohort of 153
      OTSCC patients, 131 formalin fixed paraffin embedded blocks of pre-treatment
      primary tumours were suitable for further molecular analysis. We assessed CDKN2A
      (p16) levels by immunohistochemistry (IHC), promoter methylation status by
      methylation-sensitive high resolution melting, mutation status by Sanger
      sequencing, gene copy number variation by fluorescence in situ hybridisation, and
      correlated these with patient outcome. We found that the majority of OTSCC did
      not overexpress p16 (110/116, 95%), assessed by IHC. The frequency of CDKN2A
      mutations was 20% (21/103), homozygous loss was 7% (7/97), hemizygous loss 31%
      (30/97), and promoter methylation was 18% (20/113). We found no evidence of these
      mechanisms in 24/106 (23%) p16 IHC negative tumours. No significant correlation
      was identified between any potential mechanism of CDKN2A inactivation and
      clinical features, including smoking status and age. There was a non-significant
      trend for worse overall survival for p16 IHC negative patients versus positive
      patients (HR = 1.81, 95% CI = 0.44-7.47, p = 0.40). No relationship was found
      between mechanisms of CDKN2A disruption and patient outcome. In conclusion, we
      demonstrate that CDKN2A alteration is a frequent event in OTSCC tumourigenesis.
      However, no correlation was identified between different potential mechanisms of
      CDKN2A disruption and clinical characteristics or patient outcome. 

PMID- 24436121
TI  - A pilot study of electronic directly observed therapy to improve hydroxyurea
      adherence in pediatric patients with sickle-cell disease.
AB  - BACKGROUND: Poor hydroxyurea (HU) adherence limits effective HU use in patients
      with sickle cell disease (SCD). Electronic directly observed therapy (DOT) may
      limit costs and achieve high HU adherence in children with SCD. This study aimed
      to determine if electronic DOT was feasible, acceptable, and could achieve >= 90%
      HU adherence. PROCEDURE: Children with SCD were recruited for this single
      institution, 6-month pilot study if they had been prescribed HU for >= 6 months
      and had daily access to a smartphone or computer. Participants submitted HU
      administration videos daily and received electronic reminder alerts, personalized
      feedback, and incentives to encourage adherence as part of electronic DOT.
      Primary outcomes were feasibility, participant satisfaction with electronic DOT,
      and HU adherence. Secondary outcomes included mean corpuscular volume (MCV),
      hemoglobin F percentage (HbF), and overall participant satisfaction with HU
      therapy. RESULTS: Of 15 enrolled participants, 14 completed the study.
      Satisfaction surveys showed electronic DOT reminded participants to take HU and
      could be completed in fewer than 5 minutes daily. Participants' median medication
      possession ratio at study entry improved from 0.75 (0.59-0.82) to 0.91 (0.85
      1.00) (P = 0.02) at the end of the study. Overall median observed HU adherence
      with electronic DOT was 93.3%. Median MCV and HbF increased from 96.0 to 107.2 (P
      = 0.009) and 10.5 to 11.4 (P = 0.03), respectively. CONCLUSIONS: This study
      demonstrates electronic DOT is feasible, acceptable, and can achieve high HU
      adherence. Further study is needed to confirm that electronic DOT can improve HU
      adherence and impact clinical outcomes in children with SCD.

PMID- 24436122
TI  - Hurthle cells in fine-needle aspirates of the thyroid: a review of their
      diagnostic criteria and significance.
AB  - Although the cytological assessment of Hurthle cell lesions is challenging, the
      literature offers good, albeit imperfect, guidance to aid in the crucial
      distinction between nonneoplastic and neoplastic lesions. The significance of a
      cytologic diagnosis of follicular neoplasm, Hurthle cell type, lies in the rate
      of malignancy on follow-up surgical excision, ranging in the literature from 10%
      to 45%. A cytodiagnosis of atypia of undetermined significance (AUS), Hurthle
      cell type, appears to be associated with a lower risk of malignancy on follow-up
      than other subtypes of AUS; however, this area warrants further investigation.

PMID- 24436123
TI  - Structural analysis of protein-ligand interactions: the binding of endogenous
      compounds and of synthetic drugs.
AB  - The large number of macromolecular structures deposited with the Protein Data
      Bank (PDB) describing complexes between proteins and either physiological
      compounds or synthetic drugs made it possible a systematic analysis of the
      interactions occurring between proteins and their ligands. In this work, the
      binding pockets of about 4000 PDB protein-ligand complexes were investigated and
      amino acid and interaction types were analyzed. The residues observed with lowest
      frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the
      most abundant in binding pockets. Significant differences between drug-like and
      physiological compounds were found. On average, physiological compounds establish
      with respect to drugs about twice as many hydrogen bonds with protein atoms,
      whereas drugs rely more on hydrophobic interactions to establish target
      selectivity. The large number of PDB structures describing homologous proteins in
      complex with the same ligand made it possible to analyze the conservation of
      binding pocket residues among homologous protein structures bound to the same
      ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than
      other amino acids. Also in the cases in which the same ligand is bound to
      unrelated proteins, the binding pockets showed significant conservation in the
      residue types. In this case, the probability of co-occurrence of the same amino
      acid type in the binding pockets could be up to thirteen times higher than that
      expected on a random basis. The trends identified in this study may provide an
      useful guideline in the process of drug design and lead optimization.

PMID- 24436124
TI  - Reconciliation of classical and reacted-site probability approaches to allowance
      for ligand multivalence in binding studies.
AB  - The objective of this investigation is to engender greater confidence in the
      validity of binding equations derived for multivalent ligands on the basis of
      reacted-site probability theory. To that end, a demonstration of the theoretical
      interconnection between expressions derived by the classical stepwise equilibria
      and reacted-site probability approaches for univalent ligands is followed by the
      use of the traditional stepwise procedure to derive binding equations for
      bivalent and trivalent ligands. As well as demonstrating the unwieldy nature of
      the classical binding equation for multivalent ligand systems, that exercise has
      allowed numerical simulation to be used to illustrate the equivalence of binding
      curves generated by the two approaches. The advantages of employing a redefined
      binding function for multivalent ligands are also confirmed by subjecting the
      simulated results to a published analytical procedure that has long been
      overlooked.

PMID- 24436125
TI  - Enthalpic factors override the polyelectrolyte effect in the binding of EGR1
      transcription factor to DNA.
AB  - Protein-DNA interactions are highly dependent upon salt such that the binding
      affinity precipitously decreases with increasing salt concentration in a
      phenomenon termed as the polyelectrolyte effect. In this study, we provide
      evidence that the binding of early growth response (EGR) 1 transcription factor
      to DNA displays virtually zero dependence on ionic strength under physiological
      salt concentrations and that such feat is accomplished via favorable enthalpic
      contributions. Importantly, we unearth the molecular origin of such favorable
      enthalpy and attribute it to the ability of H382 residue to stabilize the EGR1
      DNA interaction via both intermolecular hydrogen bonding and van der Waals
      contacts against the backdrop of salt. Consistent with this notion, the
      substitution of H382 residue with other amino acids faithfully restores salt
      dependent binding of EGR1 to DNA in a canonical fashion. Remarkably, H382 is
      highly conserved across other members of the EGR family, implying that changes in
      bulk salt concentration are unlikely to play a significant role in modulating
      protein-DNA interactions central to this family of transcription factors. Taken
      together, our study reports the first example of a eukaryotic protein-DNA
      interaction capable of overriding the polyelectrolyte effect.

PMID- 24436126
TI  - Investigating the binding behaviour of two avidin-based testosterone binders
      using molecular recognition force spectroscopy.
AB  - Molecular recognition force spectroscopy, a biosensing atomic force microscopy
      technique allows to characterise the dissociation of ligand-receptor complexes at
      the molecular level. Here, we used molecular recognition force spectroscopy to
      study the binding capability of recently developed testosterone binders. The two
      avidin-based proteins called sbAvd-1 and sbAvd-2 are expected to bind both
      testosterone and biotin but differ in their binding behaviour towards these
      ligands. To explore the ligand binding and dissociation energy landscape of these
      proteins, we tethered biotin or testosterone to the atomic force microscopy probe
      while the testosterone-binding protein was immobilized on the surface. Repeated
      formation and rupture of the ligand-receptor complex at different pulling
      velocities allowed determination of the loading rate dependence of the complex
      rupturing force. In this way, we obtained the molecular dissociation rate
      (k(off)) and energy landscape distances (x(beta)) of the four possible complexes:
      sbAvd-1-biotin, sbAvd-1-testosterone, sbAvd-2-biotin and sbAvd-2-testosterone. It
      was found that the kinetic off-rates for both proteins and both ligands are
      similar. In contrast, the x(beta) values, as well as the probability of complex
      formations, varied considerably. In addition, competitive binding experiments
      with biotin and testosterone in solution differ significantly for the two
      testosterone-binding proteins, implying a decreased cross-reactivity of sbAvd-2.
      Unravelling the binding behaviour of the investigated testosterone-binding
      proteins is expected to improve their usability for possible sensing
      applications.

PMID- 24436127
TI  - Dynamic identification of H2 epitopes from Leishmania (Leishmania) amazonensis
      cysteine proteinase B with potential immune activity during murine infection.
AB  - Peptides from the COOH-terminal extension of cysteine proteinase B from
      Leishmania (Leishmania) amazonensis (cyspep) can modulate immune responses in
      vertebrate hosts. With this hypothesis as base, we used the online analysis tool
      SYFPEITHI to predict seven epitopes from this region with potential to bind H2
      proteins. We performed proliferation tests and quantified reactive T lymphocytes
      applying a cytometry analysis, using samples from draining lymph node of lesions
      from L. (L.) amazonensis-infected mice. To define reactivity of T cells, we used
      complexes of DimerX (H2 D(b):Ig and H2 L(d):Ig) and the putative epitopes.
      Additionally, we applied surface plasmon resonance to verify real time
      interactions between the putative epitopes and DimerX proteins. Five peptides
      induced blastogenesis in BALB/c cells, while only two presented the same property
      in C57BL/6 mouse cells. In addition, our data indicate the existence of CD8+ T
      lymphocyte populations able to recognize each tested peptide in both murine
      strains. We observed an overlapping of results between the peptides that induced
      lymphocyte proliferation and those capable of binding to the DimerX in the
      surface plasmon resonance assays thus indicating that using these recombinant
      proteins in biosensing analyses is a promising tool to study real time molecular
      interactions in the context of major histocompatibility complex epitopes. The
      data gathered in this study reinforce the hypothesis that cyspep-derived peptides
      are important factors in the murine host infection by L. (L.) amazonensis.

PMID- 24436128
TI  - In silico and in vitro studies of cinnamaldehyde and their derivatives against
      LuxS in Streptococcus pyogenes: effects on biofilm and virulence genes.
AB  - The LuxS-based signalling pathway has an important role in physiological and
      pathogenic functions that are capable of causing different infections. In the
      present study, cinnamaldehyde (CN) and their derivatives were evaluated for their
      inhibitory efficiency against LuxS by molecular modelling, docking, dynamics and
      free-energy calculations. Sequence and structure-similarity analysis of LuxS
      protein, five different amino acids were found to be highly conserved, of which
      GLY128 was identified as the key residue involved in the effective binding of the
      ligands. Quantum-polarized ligand docking protocol showed that 2nitro and 4nitro
      CN has a higher binding efficiency than CN, which very well corroborates with the
      in vitro studies. COMSTAT analysis for the microscopic images of the S. pyogenes
      biofilm showed that the ligands have antibiofilm potential. In addition, the
      results of quantitative polymerase chain reaction (qPCR) analysis revealed that
      the transcripts treated with the compounds showed decrease in luxS expression,
      which directly reflects with the reduction in expression of speB. No substantial
      effect was observed on the virulence regulator (srv) transcript. These results
      confirm that speB is controlled by the regulation of luxS. The decreased rate of
      S. pyogenes survival in the presence of these ligands envisaged the fact that the
      compounds could readily enhance opsonophagocytosis with the reduction of
      virulence factor secretion. Thus, the overall data supports the use of CN
      derivatives against quorum sensing-mediated infections caused by S. pyogenes.

PMID- 24436131
TI  - Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU
      phosphorylation and CREB activation in Alzheimer's disease.
AB  - Genetic screening in Alzheimer's disease (AD) has identified only a handful of
      genes that are mutated in the disorder. Thus, for a very large proportion of
      patients, the biology of their disease is poorly understood. Epigenetic
      alterations may provide an explanation in these cases. Using DNA methylation
      profiles of human hippocampus from controls and patients, we have identified the
      presence of promoter hypermethylation of the dual-specificity phosphatase 22
      (DUSP22) gene in AD. DUSP22 is a likely candidate gene for involvement in the
      pathogenesis of the disorder since, as we demonstrate here, it inhibits PKA
      activity and thereby determines TAU phosphorylation status and CREB signaling.

PMID- 24436132
TI  - TERT promoter mutations predict worse survival in laryngeal cancer patients.

PMID- 24436130
TI  - The Equine PeptideAtlas: a resource for developing proteomics-based veterinary
      research.
AB  - Progress in MS-based methods for veterinary research and diagnostics is lagging
      behind compared to the human research, and proteome data of domestic animals is
      still not well represented in open source data repositories. This is particularly
      true for the equine species. Here we present a first Equine PeptideAtlas
      encompassing high-resolution tandem MS analyses of 51 samples representing a
      selection of equine tissues and body fluids from healthy and diseased animals.
      The raw data were processed through the Trans-Proteomic Pipeline to yield high
      quality identification of proteins and peptides. The current release comprises 24
      131 distinct peptides representing 2636 canonical proteins observed at false
      discovery rates of 0.2% at the peptide level and 1.4% at the protein level. Data
      from the Equine PeptideAtlas are available for experimental planning, validation
      of new datasets, and as a proteomic data mining resource. The advantages of the
      Equine PeptideAtlas are demonstrated by examples of mining the contents for
      information on potential and well-known equine acute phase proteins, which have
      extensive general interest in the veterinary clinic. The extracted information
      will support further analyses, and emphasizes the value of the Equine
      PeptideAtlas as a resource for the design of targeted quantitative proteomic
      studies. 

PMID- 24436133
TI  - The training needs of staff supporting individuals ageing with intellectual
      disability.
AB  - BACKGROUND: The issue of ageing within the cohort of people with intellectual
      disabilities has been an increasing focus for research. However, the training
      needs of the staff who support them has not been subject of extensive
      examination. MATERIALS AND METHODS: A multiround Delphi project was conducted
      focusing upon the impact ageing issues have on the support provided by disability
      workers, and what training is required to address the identified areas. RESULTS:
      Three rounds of the Delphi identified twenty-six separate important issues. A
      thematic analysis identified five main themes including Generic Training Issues;
      Medical Issues; Emerging Ageing Issues Requiring Changing Support; Mental Health
      Issues; and Quality of Life. CONCLUSIONS: The study identified a series of
      training priorities for staff assisting people ageing with an intellectual
      disability. It would appear possible for many training programmes to be developed
      and delivered with minimal cost impacts even within rural localities.

PMID- 24436134
TI  - Elevating the priority of zoo animal welfare: the chief executive as an agent of
      reform.

PMID- 24436135
TI  - The effects of combine treatment of memantine and donepezil on Alzheimer's
      disease patients and its relationship with cerebral blood flow in the prefrontal
      area.
AB  - BACKGROUND: In this study, we evaluated the effect on cognitive function of
      memantine, behavioral and psychological symptoms of dementia, and the care
      burden, in patients with moderate-to-severe Alzheimer's disease (AD).
      Furthermore, with near-infrared spectroscopy (NIRS), we examined the association
      between effect of memantine and brain blood flow. METHODS: We evaluated the
      effect of memantine administration from baseline on Clinical Global Impression
      Improvement scale, mini mental state examination (MMSE), Clock Drawing Test
      (CDT), Neuropsychiatric Inventory (NPI), Japanese version of the Zarit Burden
      Interview (J-ZBI) and NIRS in two groups, donepezil administration memantine
      combination group (combination group, n = 19) donepezil administration memantine
      non-administration group (control group, n = 18) were assessed at weeks 0, 4, 12,
      and 24. RESULTS: Significant difference was found between the combination group
      and the control group in the score variation of Clinical Global Impression
      Improvement scale, MMSE, CDT, NPI, and J-ZBI. In the NIRS measurements, trend
      oxyhemoglobin reduced suppression was observed in some channels centered on the
      superior frontal gyrus. A significant correlation was observed in the scores of
      MMSE, CDT, NPI, and J-ZBI. In addition, a significant positive correlation was
      also observed between the number of words in NIRS and scores of MMSE and CDT.
      CONCLUSIONS: In this study, by administering memantine in AD patients that
      inhibit the reduction of cerebral blood flow in the prefrontal area and improve
      clinical symptoms overall cognitive function, behavioral and psychological
      symptoms of dementia, thereby reducing the care burden of caregivers was
      suggested.

PMID- 24436136
TI  - Prevalence and characteristics of moderate to severe fatigue: a multicenter study
      in cancer patients and survivors.
AB  - BACKGROUND: The effective management of fatigue in patients with cancer requires
      a clear delineation of what constitutes nontrivial fatigue. The authors defined
      numeric cutpoints for fatigue severity based on functional interference and
      described the prevalence and characteristics of fatigue in patients with cancer
      and survivors. METHODS: In a multicenter study, outpatients with breast,
      prostate, colorectal, or lung cancer rated their fatigue severity and symptom
      interference with functioning on the M. D. Anderson Symptom Inventory numeric
      scale of 0 to 10. Ratings of symptom interference guided the selection of numeric
      rating cutpoints between mild, moderate, and severe fatigue levels. Regression
      analysis identified significant factors related to reporting moderate=severe
      fatigue . RESULTS: The statistically optimal cutpoints were 4 for moderate
      fatigue and 7 for severe fatigue. Moderate=severe fatigue was reported by 983 of
      2177 patients (45%) undergoing active treatment and was more likely to occur in
      patients receiving treatment with strong opioids (odds ratio [OR], 3.00), those
      with a poor Eastern Cooperative Oncology Group performance status (OR, 2.00),
      those who had >5% weight loss within 6 months (OR, 1.60), those who were
      receiving >10 medications (OR, 1.58), those with lung cancer (OR, 1.55), and
      those with a history of depression (OR, 1.42). Among survivors (patients with
      complete remission or no evidence of disease, and not currently receiving cancer
      treatment), 29% of patients (150 of 515 patients) had moderate=severe fatigue
      that was associated with poor performance status (OR, 3.48) and a history of
      depression (OR, 2.21). CONCLUSIONS: The current study statistically defined
      fatigue severity categories related to significantly increased symptom
      interference. The high prevalence of moderate=severe fatigue in both actively
      treated patients with cancer and survivors warrants the promoting of the routine
      assessment and management of patient-reported fatigue.

PMID- 24436137
TI  - Differential changes in gene expression in human brain during late first
      trimester and early second trimester of pregnancy.
AB  - OBJECTIVE: This study aimed to describe brain development during the first (B1)
      and second trimester (B3) in human fetuses. DESIGN: Ten brains from 10 to 18
      weeks of gestational age (GA) were collected, and the RNA was used for
      transcriptome analysis (Affymetrix 1.0 ST microarray chip). Differences in brain
      development within 10 to 18 GA were investigated by dividing the sample into 10
      to 12 (B1), 13 to 15(B2) and 16 to 18(B3) weeks. A fold change of 2 or above,
      with a false discovery rate of 5%, was used as cut-off to determine differential
      gene expression for individual genes. Quantitative real-time PCR was used to
      confirm differences. Tests for enrichment procedures (using Gene Ontology and
      Kyoto Encyclopedia of Genes and Genomes) were then used to identify functional
      groups of mRNA. RESULTS: At 10 to 12 weeks, brains showed neuronal migration to
      be upregulated. From 10 to 18 weeks, brains showed genes coding for neuronal
      migration, differentiation and connectivity upregulated. ALDH1A1 and NPY genes,
      marker of spinal cord and striatum, were upregulated in B1 and B3 brains,
      respectively. Also, SLITRK6-HAS2 and CRYAB-PCDH18 genes for ear and eye sensory
      input were upregulated in B1. CONCLUSIONS: For the first time, brain global gene
      expression was described in human samples. Period B1 was dominated by genes
      coding for neuronal migration, differentiation, programmed cell death and sensory
      organs. B3 was dominated by neuronal proliferation, branching and myelination.
      Creating such a database will allow comparison with abnormals in future studies.

PMID- 24436138
TI  - Fit4Life: a weight loss intervention for children who have survived childhood
      leukemia.
AB  - BACKGROUND: Children surviving acute lymphoblastic leukemia (ALL) are at
      increased risk for overweight and obesity over that of the general population.
      Whether a generic or tailored approach to weight management is needed for cancer
      survivors has yet to be tested. PROCEDURE: Thirty-eight youth 8-18 years with BMI
      >= 85% who had survived ALL were recruited for a randomized clinical trial
      evaluating a weight management intervention (WMI) tailored for childhood ALL
      survivors (Fit4Life). Fit4Life recipients received a 4-month web, phone, and text
      message-delivered WMI tailored for cancer survivorship. Controls received a
      general WMI delivered via phone and mail. Assessments were performed at baseline
      and 4 months. Outcome data were analyzed according to assigned treatment
      condition over time. RESULTS: Most (80%, (70%, 100%) [median (IQR)]) of the
      assigned curriculum was received by Fit4Life participants as compared to 50%
      (40%, 65%) among controls. Fit4Life recipients >= 14 years demonstrated less
      weight gain (P = 0.05) and increased moderate-to-vigorous physical activity (P <
      0.01) while all Fit4Life recipients reported reduced negative mood (P < 0.05)
      over time as compared to control counterparts. CONCLUSIONS: We demonstrated
      acceptable feasibility of a WMI tailored for overweight and obese children
      surviving ALL utilizing a multimodal technology approach. Improved weight, weight
      related behavior, and psychological outcomes were demonstrated among Fit4Life
      intervention as compared to youth receiving a generic WMI. Data from this pilot
      trial may be used to design a larger trial to determine whether youth of all ages
      also can derive a benefit from a cancer survivor-tailored WMI and whether short
      term outcomes translate into improved long-term outcomes for childhood ALL
      survivors.

PMID- 24436139
TI  - The carcinogenic effects of aspartame: The urgent need for regulatory re
      evaluation.
AB  - Aspartame (APM) is an artificial sweetener used since the 1980s, now present in
      >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965,
      and its first approval by the US Food and Drugs Administration (FDA) in 1981, the
      safety of APM, and in particular its carcinogenicity potential, has been
      controversial. The present commentary reviews the adequacy of the design and
      conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the
      1970s, to the FDA for market approval. We also review how experimental and
      epidemiological data on the carcinogenic risks of APM, that became available in
      2005 motivated the European Commission (EC) to call the European Food and Safety
      Authority (EFSA) for urgent re-examination of the available scientific
      documentation (including the Searle studies). The EC has further requested that,
      if the results of the evaluation should suggest carcinogenicity, major changes
      must be made to the current APM specific regulations. Taken together, the studies
      performed by G.D. Searle in the 1970s and other chronic bioassays do not provide
      adequate scientific support for APM safety. In contrast, recent results of life
      span carcinogenicity bioassays on rats and mice published in peer-reviewed
      journals, and a prospective epidemiological study, provide consistent evidence of
      APM's carcinogenic potential. On the basis of the evidence of the potential
      carcinogenic effects of APM herein reported, a re-evaluation of the current
      position of international regulatory agencies must be considered an urgent matter
      of public health.

PMID- 24436140
TI  - Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the
      development of polycystic liver diseases.
AB  - OBJECTIVE: Polycystic liver diseases (PCLDs) are genetic disorders characterised
      by progressive bile duct dilatation and/or cyst development. Their pathogenesis
      is a consequence of hyperproliferation, hypersecretion and microRNA alterations
      in cholangiocytes. Here we evaluate the role of matrix metalloproteases (MMPs) in
      the hepatic cystogenesis of PCLDs. DESIGN: Metalloprotease activity was measured
      by microfluorimetric assays in normal and polycystic cholangiocyte cultures from
      humans and rats, and gene expression by real time quantitative PCR. The role of
      cytokines, oestrogens and growth factors present in the cystic fluid of PCLD
      patients was evaluated for MMP activity. The MMP inhibitor marimastat was
      examined for cystic expansion in vitro and in polycystic kidney (PCK) rats.
      RESULTS: Polycystic human and rat cholangiocytes displayed increased MMP
      activity, which was associated with increased mRNA levels of different MMPs.
      Interleukin (IL)-6 and IL-8, and 17beta-oestradiol, all stimulated MMP activity
      in human cholangiocytes. The presence of antibodies against IL-6 and/or IL-8
      receptor/s inhibited baseline MMP hyperactivity of polycystic human
      cholangiocytes but had no effect on normal human cholangiocytes. MMP-3 was
      overexpressed in cystic cholangiocytes from PCLD human and PCK rat livers by
      immunohistochemistry. Marimastat reduced MMP hyperactivity of polycystic human
      and rat cholangiocytes and blocked the cystic expansion of PCK cholangiocytes
      cultured in three-dimensions. Chronic treatment of 8-week-old PCK rats with
      marimastat inhibited hepatic cystogenesis and fibrosis. CONCLUSIONS: PCLDs are
      associated with cholangiocyte MMP hyperactivity resulting from
      autocrine/paracrine stimulation by IL-6 and IL-8. Inhibition of this MMP
      hyperactivity with marimastat decreased hepatic cystogenesis in vitro and in an
      animal model of PCLD, offering a potential therapeutic tool.

PMID- 24436143
TI  - Changes in staging and advances in treatment for gynecological malignancies: the
      impact on cytopathology.

PMID- 24436141
TI  - Bacterial protein signals are associated with Crohn's disease.
AB  - OBJECTIVE: No Crohn's disease (CD) molecular maker has advanced to clinical use,
      and independent lines of evidence support a central role of the gut microbial
      community in CD. Here we explore the feasibility of extracting bacterial protein
      signals relevant to CD, by interrogating myriads of intestinal bacterial
      proteomes from a small number of patients and healthy controls. DESIGN: We first
      developed and validated a workflow-including extraction of microbial communities,
      two-dimensional difference gel electrophoresis (2D-DIGE), and LC-MS/MS-to
      discover protein signals from CD-associated gut microbial communities. Then we
      used selected reaction monitoring (SRM) to confirm a set of candidates. In
      parallel, we used 16S rRNA gene sequencing for an integrated analysis of gut
      ecosystem structure and functions. RESULTS: Our 2D-DIGE-based discovery approach
      revealed an imbalance of intestinal bacterial functions in CD. Many proteins,
      largely derived from Bacteroides species, were over-represented, while under
      represented proteins were mostly from Firmicutes and some Prevotella members.
      Most overabundant proteins could be confirmed using SRM. They correspond to
      functions allowing opportunistic pathogens to colonise the mucus layers, breach
      the host barriers and invade the mucosae, which could still be aggravated by
      decreased host-derived pancreatic zymogen granule membrane protein GP2 in CD
      patients. Moreover, although the abundance of most protein groups reflected that
      of related bacterial populations, we found a specific independent regulation of
      bacteria-derived cell envelope proteins. CONCLUSIONS: This study provides the
      first evidence that quantifiable bacterial protein signals are associated with
      CD, which can have a profound impact on future molecular diagnosis.

PMID- 24436142
TI  - CCL20/CCR6-mediated migration of regulatory T cells to the Helicobacter pylori
      infected human gastric mucosa.
AB  - BACKGROUND: Helicobacter pylori-induced peptic ulceration is less likely to occur
      in patients with a strong gastric anti-inflammatory regulatory T cell (Treg)
      response. Migration of Tregs into the gastric mucosa is therefore important.
      OBJECTIVE: To identify the homing receptors involved in directing Tregs to the
      gastric mucosa, and investigate how H pylori stimulates the relevant chemokine
      responses. DESIGN: Gastric biopsy samples and peripheral blood were donated by 84
      H pylori-infected and 46 uninfected patients. Luminex assays quantified gastric
      biopsy chemokine concentrations. Flow cytometry was used to characterise homing
      receptors on CD4(+)CD25(hi) Tregs. H pylori wild-type and isogenic mutants were
      used to investigate the signalling mechanisms behind CCL20 and IL-8 induction in
      gastric epithelial cell lines. Transwell assays were used to quantify Treg
      migration towards chemokines in vitro. RESULTS: CCL20, CXCL1-3 and IL-8
      concentrations were significantly increased in gastric biopsy samples from H
      pylori-infected patients. CCR6 (CCL20 receptor), CXCR1 and CXCR2 (IL-8 and CXCL1
      3 receptors) were expressed by a higher proportion of peripheral blood Tregs in
      infected patients. Most gastric Tregs expressed these receptors. H pylori induced
      CCL20 production by gastric epithelial cells via cag pathogenicity island
      (cagPAI)-dependent NF-kappaB signalling. Foxp3(+), but not Foxp3(-), CD4 cells
      from infected mice migrated towards recombinant CCL20 in vitro. CONCLUSIONS: As
      well as increasing Treg numbers, H pylori infection induces a change in their
      characteristics. Expression of CCR6, CXCR1 and CXCR2 probably enables their
      migration towards CCL20 and IL-8 in the infected gastric mucosa. Such qualitative
      changes may also explain how H pylori protects against some extragastric
      inflammatory disorders.

PMID- 24436144
TI  - Cell wall proteomics of sugarcane cell suspension cultures.
AB  - The use of cell walls to produce cellulosic ethanol from sugarcane bagasse is a
      new challenge. A better knowledge of proteins involved in cell wall remodelling
      is essential to improve the saccharification processes. Cell suspension cultures
      were used for this first cell wall proteomics study of sugarcane. Proteins
      extracted from cell walls were identified using an adapted protocol. They were
      extracted using 0.2 M CaCl2 and 2 M LiCl after purification of cell walls. The
      proteins were then identified by the innovative nanoACQUITY UPLC MS/MS technology
      and bioinformatics using the translated SUCEST EST cluster database of sugarcane.
      The experiments were reproduced three times. Since Sorghum bicolor is the closest
      plant with a fully sequenced genome, homologous proteins were searched for to
      complete the annotation of proteins, that is, prediction of subcellular
      localization and functional domains. Altogether, 69 different proteins predicted
      to be secreted were identified among 377 proteins. The reproducibility of the
      experiments is discussed. These proteins were distributed into eight functional
      classes. Oxidoreductases such as peroxidases were well represented, whereas
      glycoside hydrolases were scarce. This work provides information about the
      proteins that could be manipulated through genetic transformation, to increase
      second-generation ethanol production. 

PMID- 24436145
TI  - The influence of organic production on food quality - research findings, gaps and
      future challenges.
AB  - Although several meta-analysis studies have been published comparing the quality
      of food derived from organic and non-organic origin, it is still not clear if
      food from organic production per se can guarantee product-related added value to
      consumers. This paper aims to summarize the status quo in order to identify
      research gaps and suggest future research challenges. Organic food is described
      according to a quality model already published. The influence of organic
      production on food quality is structured in primary production and processing.
      Furthermore, organic food authentication is discussed. Organic food seems to
      contain fewer pesticide residues and statistically more selected health-related
      compounds such as polyphenols in plant products and polyunsaturated fatty acids
      in milk and meat products, but the health relevance for consumers is not clear
      yet. Comparing food from organic origin with so called 'conventional' food seems
      not to be appropriate, because 'conventional' is not defined. In organic food
      quality research a system approach is needed from which systemic markers can be
      selected. Research on the impact of processing technologies on the quality
      according to organic principles seems of high relevance, since most of the food
      is processed.

PMID- 24436146
TI  - Ultrasound imaging of the pelvic floor: changes in anatomy during and after first
      pregnancy.
AB  - OBJECTIVES: To describe changes in the absolute values of levator hiatal
      dimensions and in the contractility and distensibility of the levator hiatus
      during pelvic floor contraction and Valsalva maneuver, using three/four
      dimensional (3D/4D) transperineal ultrasound in women during and after their
      first pregnancy. METHODS: Two-hundred and eighty nulliparous pregnant women
      underwent ultrasound examination at 12 and 36 weeks' gestation and 6 months
      postpartum. Hiatal dimensions were measured at rest, on pelvic floor contraction
      and on Valsalva maneuver. The contractility and distensibility were determined by
      the difference between hiatal dimensions at rest and those on contraction or
      Valsalva, respectively. After exclusions, there were 231 datasets from women at
      rest, 199 for pelvic floor contraction and 230 for Valsalva maneuver. Data at 36
      weeks' gestation and 6 months postpartum were compared with data at 12 weeks'
      gestation. RESULTS: At 36 weeks' gestation, the absolute values of hiatal
      dimensions and the contractility and distensibility of the levator hiatus were
      significantly increased compared with those at 12 weeks' gestation. Women who
      delivered vaginally showed a persistent significant increase in hiatal dimensions
      on Valsalva, whereas women who delivered by prelabor or first-stage Cesarean
      section showed no significant changes in hiatal dimensions on Valsalva. After
      both vaginal and Cesarean section delivery, there was a persistent increase in
      the distensibility of the hiatus during Valsalva compared with in early
      pregnancy. CONCLUSION: During first pregnancy, the absolute values of levator
      hiatal dimensions and the contractility and distensibility of the levator hiatus
      increase. Regardless of delivery mode, increased distensibility of the levator
      hiatus during Valsalva persists after childbirth. This increased pelvic floor
      distensibility may play a role in the development of pelvic floor dysfunction in
      later life.

PMID- 24436147
TI  - Intra-articular injection of rhFGF-18 improves the healing in microfracture
      treated chondral defects in an ovine model.
AB  - Microfracture is a common cartilage repair procedure. Strategies to improve
      healing post-microfracture include the use of growth factors to enhance hyaline
      cartilage production. This study investigates the effect of intra-articular
      recombinant human fibroblastic growth factor 18 (rhFHF18) on the healing of a
      chondral defect treated with microfracture in an ovine model. Chondral defects (8
      mm diameter) were created in the medial femoral condyle of 80 sheep (n =
      16/treatment group). Defects were treated with microfracture alone or
      microfracture + intra-articular rhFGF-18 (administered either as one or two
      cycles of 3* weekly injections). Outcome measures included mechanical testing,
      macroscopic International Cartilage Repair Society repair score, modified
      O'Driscoll histology score, qualitative histology, and immunohistochemistry for
      types I, II, and VI collagen. In treated animals, there was a statistically
      significant improvement in ICRS tissue repair score and tissue infill score, in
      the modified O'Driscoll score between control and 1 cycle of rhFGF-18 at 6 m, and
      in the cartilage repair score and structural characteristic score between the
      control and both rhFGF-18 groups at 6 m. There was no evidence of degeneration of
      adjacent cartilage in the rhFGF-18 treated cartilage. The increase in hyaline
      cartilage-like tissue formed in the microfracture + rhFGF-18 treated groups
      indicates that rhFGF-18 potentiates the formation of hyaline cartilage repair
      following microfracture.

PMID- 24436148
TI  - Suppression of microRNA-9 by mutant EGFR signaling upregulates FOXP1 to enhance
      glioblastoma tumorigenicity.
AB  - The EGF receptor (EGFR) is amplified and mutated in glioblastoma, in which its
      common mutation (DeltaEGFR, also called EGFRvIII) has a variety of activities
      that promote growth and inhibit death, thereby conferring a strong tumor
      enhancing effect. This range of activities suggested to us that DeltaEGFR might
      exert its influence through pleiotropic effectors, and we hypothesized that
      microRNAs might serve such a function. Here, we report that DeltaEGFR
      specifically suppresses one such microRNA, namely miR-9, through the Ras/PI3K/AKT
      axis that it is known to activate. Correspondingly, expression of miR-9
      antagonizes the tumor growth advantage conferred by DeltaEGFR. Silencing of
      FOXP1, a miR-9 target, inhibits DeltaEGFR-dependent tumor growth and, conversely,
      de-repression of FOXP1, as a consequence of miR-9 inhibition, increases
      tumorigenicity. FOXP1 was sufficient to increase tumor growth in the absence of
      oncogenic DeltaEGFR signaling. The significance of these findings is underscored
      by our finding that high FOXP1 expression predicts poor survival in a cohort of
      131 patients with glioblastoma. Collectively, these data suggest a novel
      regulatory mechanism by which DeltaEGFR suppression of miR-9 upregulates FOXP1 to
      increase tumorigenicity.

PMID- 24436149
TI  - CD133+ cancer stem-like cells in small cell lung cancer are highly tumorigenic
      and chemoresistant but sensitive to a novel neuropeptide antagonist.
AB  - Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor
      survival rates, with initial responses nearly invariably followed by rapid
      recurrence of therapy-resistant disease. Drug resistance in SCLC may be
      attributable to the persistence of a subpopulation of cancer stem-like cells
      (CSC) that exhibit multiple drug resistance. In this study, we characterized the
      expression of CD133, one important marker of CSC in other cancers, in SCLC cancer
      cells. CD133 expression correlated with chemoresistance and increased
      tumorigenicity in vitro and in vivo accompanied by increased expression of
      Akt/PKB and Bcl-2. CD133 expression was increased in mouse and human SCLC after
      chemotherapy, an observation confirmed in clinical specimens isolated
      longitudinally from a patient receiving chemotherapy. We discovered in CD133(+)
      SCLC cells, an increased expression of the mitogenic neuropeptide receptors for
      gastrin-releasing peptide and arginine vasopressin. Notably, these cells
      exhibited increased sensitivity to the growth inhibitory and proapoptotic effects
      of a novel broad spectrum neuropeptide antagonist (related to SP-G), which has
      completed a phase I clinical trial for SCLC. Our results offer evidence that this
      agent can preferentially target chemoresistant CD133(+) cells with CSC character
      in SCLC, emphasizing its potential utility for improving therapy in this setting.

PMID- 24436150
TI  - Whole-body simultaneous positron emission tomography (PET)-MR: optimization and
      adaptation of MRI sequences.
AB  - The purpose of this article is to introduce the underlying challenges associated
      with the incorporation of magnetic resonance imaging (MRI) into the new hybrid
      imaging modality simultaneous positron emission tomography (PET)/MR and their
      impact on attenuation correction, sequence optimization, and protocol
      development. Many adjustments to MR sequences are necessary for optimal whole
      body and fused image results.

PMID- 24436151
TI  - Lanthanide-doped LiLuF(4) upconversion nanoprobes for the detection of disease
      biomarkers.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great promise in
      bioapplications. Exploring new host materials to realize efficient upconversion
      luminescence (UCL) output is a goal of general concern. Herein, we develop a
      unique strategy for the synthesis of novel LiLuF4 :Ln(3+) core/shell UCNPs with
      typically high absolute upconversion quantum yields of 5.0 % and 7.6 % for Er(3+)
      and Tm(3+) , respectively. Based on our customized UCL biodetection system, we
      demonstrate for the first time the application of LiLuF4 :Ln(3+) core/shell UCNPs
      as sensitive UCL bioprobes for the detection of an important disease marker beta
      subunit of human chorionic gonadotropin (beta-hCG) with a detection limit of 3.8
      ng mL(-1) , which is comparable to the beta-hCG level in the serum of normal
      humans. Furthermore, we use these UCNPs in proof-of-concept computed tomography
      imaging and UCL imaging of cancer cells, thus revealing the great potential of
      LiLuF4 :Ln(3+) UCNPs as efficient nano-bioprobes in disease diagnosis. 

PMID- 24436152
TI  - Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use
      trial.
AB  - BACKGROUND: L-Asparaginase is an integral component of standard chemotherapy
      regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical
      hypersensitivity, a common reason for treatment discontinuation, has been
      reported in 10-30% of patients receiving Escherichia coli-derived asparaginase.
      After hypersensitivity, E. coli-derived asparaginase should be discontinued and
      an alternative asparaginase preparation, such as asparaginase Erwinia
      chrysanthemi, may be initiated. We conducted a compassionate-use study to collect
      additional safety information on asparaginase Erwinia chrysanthemi and to support
      FDA approval of the product. PROCEDURE: Patients with ALL or lymphoblastic
      lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade >=2) to
      an E. coli-derived asparaginase participated in this trial. The recommended
      asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week
      (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E.
      coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated
      asparaginase dose for the completion of their planned asparaginase treatment.
      RESULTS: Adverse event reports and/or case report forms were completed for 940
      patients. The most common adverse event (AE) was hypersensitivity (13.6%).
      Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed
      their planned asparaginase treatment with asparaginase Erwinia chrysanthemi.
      There was no apparent difference in the incidence of the most commonly reported
      AEs with asparaginase treatment by age, administration, or disease state.
      CONCLUSIONS: This study further established the safety profile of asparaginase
      Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity
      reaction to an E. coli-derived asparaginase.

PMID- 24436153
TI  - Rapid cervical phIGFBP-1 test in asymptomatic twin pregnancies: role in mid
      pregnancy prediction of spontaneous preterm delivery.
AB  - Objective This study aimed to assess the accuracy of a second-trimester rapid
      cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1)
      test to predict spontaneous preterm delivery in asymptomatic twin pregnancies.
      Method During the second trimester, a rapid test to detect phIGFBP-1 in cervical
      secretions was performed on consecutive twin pregnancies between 2009 and 2011,
      to evaluate its predictive value for spontaneous preterm delivery at <28, <30,
      <32 and <34 weeks' gestation. Excluded were patients with cerclage, pessary or
      undergoing indicated preterm delivery. Results A total of 197 pregnancies
      fulfilled the study criteria and were tested at a median gestational age of 20.3
      weeks (interquartile range: 20-20.6). Median gestational age at delivery was 36.4
      weeks. Spontaneous preterm delivery at <34 weeks occurred in 21 (10.7%) cases, at
      <32 weeks in 9 (4.5%), at <30 weeks in 6 (3%) and at <28 weeks in 4 (2%).
      Seventeen patients (8.7%) were test positive: In this group, three patients
      delivered before 34 weeks' gestation, whereas none delivered at <32 weeks. The
      sensitivity, specificity, positive and negative predictive value of the test for
      spontaneous preterm delivery <34 weeks were 14% (95% confidence interval, 3-37%),
      92% (86-95%), 17% (4-44%) and 90% (84-93%), respectively, with a positive and
      negative likelihood ratio of 1.79 (0.56-5.74) and 0.93 (0.78-1.10). Conclusions
      In the second trimester, rapid cervical phIGFBP-1 testing in asymptomatic twin
      pregnancies has a poor performance in predicting spontaneous preterm delivery.

PMID- 24436154
TI  - Characterization of the guinea pig animal model and subsequent comparison of the
      behavioral effects of selective dopaminergic drugs and methamphetamine.
AB  - Although not commonly used in behavior tests guinea pigs may offer subtle
      behavior repertoires that better mimic human activity and warrant study. To test
      this, 31 Hartley guinea pigs (male, 200-250 g) were evaluated in PhenoTyper cages
      using the video-tracking EthoVision XT 7.0 software. Results showed that guinea
      pigs spent more time in the hidden zone (small box in corner of cage) than the
      food/water zone, or arena zone. Guinea pigs exhibited thigmotaxis (a wall
      following strategy) and were active throughout the light and dark phases. Eating
      and drinking occurred throughout the light and dark phases. An injection of 0.25
      mg/kg SCH23390, the dopamine D1 receptors (D1R) antagonist, produced significant
      decreases in time spent in the hidden zone. There were insignificant changes in
      time spent in the hidden zone for guinea pigs treated with 7.5 mg SKF38393 (D1R
      agonist), 1.0 mg/kg sulpiride (D2R antagonist), and 1.0 or 10.0 mg/kg
      methamphetamine. Locomotor activity profiles were unchanged after injections of
      saline, SKF38393, SCH23390, and sulpiride. By contrast, a single injection or
      repeated administration for 7 days of low-dose methamphetamine induced transient
      hyperactivity but this declined to baseline levels over the 22-h observation
      period. Guinea pigs treated with high-dose methamphetamine displayed sustained
      hyperactivity and travelled significantly greater distances over the circadian
      cycle. Subsequent 7-day treatment with high-dose methamphetamine induced motor
      sensitization and significant increases in total distances moved relative to
      single drug injections or saline controls. These results highlight the
      versatility and unique features of the guinea pig for studying brain-behavior
      interactions.

PMID- 24436155
TI  - Enterolactone concentrations and prognosis after postmenopausal breast cancer:
      assessment of effect modification and meta-analysis.
AB  - We previously reported that high concentrations of enterolactone, a lignan
      metabolite, are associated with lower mortality in 1,140 breast cancer patients
      from Germany. Using an extended set of 2,182 patients aged 50-74 years at
      diagnosis (2001-2005) and prospectively followed up until 2009, we investigated
      whether the association with mortality differs by lifestyle factors and tumor
      characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) were
      estimated using multivariable Cox regression. Potential differential effects by
      tumor characteristics and lifestyle factors were assessed and a meta-analysis of
      five studies addressing lignan exposure and breast cancer prognosis was performed
      to summarize evidence. Median enterolactone concentrations were 17.4 (+/- 30.5
      standard deviation) and 22.9 nmol L(-1) (+/- 44.8), respectively, for 269
      deceased and 1,913 patients still alive. High enterolactone concentrations were
      significantly associated with lower all-cause mortality (per 10 nmol L(-1) : HR
      0.94, 95% CI 0.90-0.98), breast cancer-specific mortality (HR 0.94, 0.89-0.99),
      and distant disease-free survival (HR 0.94, 0.90-0.98). Associations were found
      for stage 0-IIIA but not for stage IIIB-IV disease (p(het) = 0.01) and were
      stronger in patients with BMI <25 kg m(-2) than those with BMI >= 25 (p(het) =
      0.04). In patients with healthy lifestyle (BMI <25, nonsmoker, physically
      active), the inverse association with all-cause mortality was still apparent (HR
      0.92, 0.85-0.99). The meta-analysis yielded significant associations both for all
      cause (HR 0.57, 0.42-0.78) and breast cancer-specific mortality (HR 0.54, 0.39
      0.75). Our findings show that high lignan exposure is associated with reduced
      mortality in breast cancer patients. The inverse association observed in this
      study cannot be entirely explained by a healthy lifestyle.

PMID- 24436156
TI  - Examining occupational health and safety disparities using national data: a cause
      for continuing concern.
AB  - BACKGROUND: Occupational status, a core component of socioeconomic status, plays
      a critical role in the well-being of U.S. workers. Identifying work-related
      disparities can help target prevention efforts. METHODS: Bureau of Labor
      Statistics workplace data were used to characterize high-risk occupations and
      examine relationships between demographic and work-related variables and
      fatality. RESULTS: Employment in high-injury/illness occupations was
      independently associated with being male, Black, <=high school degree, foreign
      birth, and low-wages. Adjusted fatal occupational injury rate ratios for 2005
      2009 were elevated for males, older workers, and several industries and
      occupations. Agriculture/forestry/fishing and mining industries and
      transportation and materials moving occupations had the highest rate ratios.
      Homicide rate ratios were elevated for Black, American Indian/Alaska
      Native/Asian/Pacific Islanders, and foreign-born workers. CONCLUSIONS: These
      findings highlight the importance of understanding patterns of disparities of
      workplace injuries, illnesses and fatalities. Results can improve intervention
      efforts by developing programs that better meet the needs of the increasingly
      diverse U.S. workforce.

PMID- 24436157
TI  - Uncovering nativity disparities in cancer patterns: Multiple imputation strategy
      to handle missing nativity data in the Surveillance, Epidemiology, and End
      Results data file.
AB  - BACKGROUND: Although birthplace data are routinely collected in the participating
      Surveillance, Epidemiology, and End Results (SEER) registries, such data are
      missing in a nonrandom manner for a large percentage of cases. This hinders
      analysis of nativity-related cancer disparities. In the current study, the
      authors evaluated multiple imputation of nativity status among Hispanic patients
      diagnosed with cervical, prostate, and colorectal cancer and demonstrated the
      effect of multiple imputation on apparent nativity disparities in survival.
      METHODS: Multiple imputation by logistic regression was used to generate nativity
      values (US-born vs foreign-born) using a priori-defined variables. The accuracy
      of the method was evaluated among a subset of cases. Kaplan-Meier curves were
      used to illustrate the effect of imputation by comparing survival among US-born
      and foreign-born Hispanics, with and without imputation of nativity. RESULTS:
      Birthplace was missing for 31%, 49%, and 39%, respectively, of cases of cervical,
      prostate, and colorectal cancer. The sensitivity of the imputation strategy for
      detecting foreign-born status was >=90% and the specificity was >=86%. The
      agreement between the true and imputed values was >=0.80 and the
      misclassification error was <=10%. Kaplan-Meier survival curves indicated
      different associations between nativity and survival when nativity was imputed
      versus when cases with missing birthplace were omitted from the analysis.
      CONCLUSIONS: Multiple imputation using variables available in the SEER data file
      can be used to accurately detect foreign-born status. This simple strategy may
      help researchers to disaggregate analyses by nativity and uncover important
      nativity disparities in regard to cancer diagnosis, treatment, and survival.

PMID- 24436161
TI  - Online only - ready for the change!

PMID- 24436163
TI  - Etiology of surgical site infections after primary total joint arthroplasties.
AB  - We sought to characterize the causative pathogens of surgical site infections
      (SSIs) following primary total joint arthroplasties and to evaluate trends in the
      microbial etiology. We analyzed the etiology of SSIs following 2,632 total hip
      arthroplasty and knee arthroplasty procedures performed at our institution from
      2004 through 2010. We calculated the annual proportion of SSIs accounted for each
      of the most common organisms and evaluated trends using the chi(2) test for
      trend. SSIs were identified in 111 procedures (4.2%). The annual incidence of
      SSIs did not change significantly during the study period. Staphylococci were the
      most common cause of infection (59.6%) and most of infections were monomicrobial
      (82.8%). From 2004 to 2010, the annual proportion of infections due to gram
      negative bacilli (GNB) increased from 21.4% to 66.7% (p = 0.085 for trend). This
      increase was accompanied by a decline in the proportion of SSIs from coagulase
      negative staphylococci (p = 0.003). Additionally, we found an increase in the
      percentage of polymicrobial infections (from 7.1% in 2004 to 41.7% in 2010, p =
      0.014). Multivariate analysis corroborated these trends. Our study reports an
      emergence of GNB as a cause of SSIs after primary total joint arthroplaties and
      an increase of polymicrobial infections.

PMID- 24436164
TI  - Early extremity MRI findings and pathological synovial changes in antigen-induced
      arthritis rabbit model.
AB  - PURPOSE: To investigate the association between early extremity MRI (E-MRI)
      findings and synovial pathological changes in antigen-induced arthritis (AIA)
      rabbit model. MATERIALS AND METHODS: AIA was successfully induced in the right
      knee of 32 sensitized Japanese white rabbits, which were then divided into four
      groups according to the time of killing after AIA induction: 1-week (Group A), 2
      weeks (Group B), 3-weeks (Group C), and 4-weeks (Group D); the left knee served
      as control in each rabbit. RESULTS: There were varying degrees of joint effusion
      in all AIA groups. E-MRI scan showed low signal in T1-weighted images (T1Wi) and
      high signal in T2-weighted images (T2Wi). Enhanced E-MRI revealed elevated
      synovial signal at the right knee in the three-dimensional spoiled gradient T1WI,
      showing linear and band-shaped, diffuse hyperintensity. Histological examination
      of right knees found scattered inflammatory cell infiltration, swelling, and
      proliferation of the synovial cells at 7 days after AIA induction and dispersed
      and disordered proliferation of synovial cells up to 3 layers at 28 days
      postinduction. The synovial enhancement of right knee E-MRI was consistent with a
      synovial pathology score for all rabbits (Kappa = 0.965, P < 0.01). CONCLUSION: E
      MRI can reveal the degree of changes in the joints and synovium at different
      periods of the AIA model.

PMID- 24436158
TI  - Serum influences the expression of Pseudomonas aeruginosa quorum-sensing genes
      and QS-controlled virulence genes during early and late stages of growth.
AB  - In response to diverse environmental stimuli at different infection sites,
      Pseudomonas aeruginosa, a serious nosocomial pathogen, coordinates the production
      of different virulence factors through a complicated network of the hierarchical
      quorum-sensing (QS) systems including the las, rhl, and the 2-alkyl-4-quinolone
      related QS systems. We recently showed that at early stages of growth serum
      alters the expression of numerous P. aeruginosa genes. In this study, we utilized
      transcriptional analysis and enzyme assays to examine the effect of serum on the
      QS and QS-controlled virulence factors during early and late phases of growth of
      the P. aeruginosa strain PAO1. At early phase, serum repressed the transcription
      of lasI, rhlI, and pqsA but not lasR or rhlR. However, at late phase, serum
      enhanced the expression of all QS genes. Serum produced a similar effect on the
      synthesis of the autoinducers 3OC12-HSL, C4-HSL, and HHQ/PQS. Additionally, serum
      repressed the expression of several QS-controlled genes in the early phase, but
      enhanced them in the late phase. Furthermore, serum influenced the expression of
      different QS-positive (vqsR, gacA, and vfr) as well as QS-negative (rpoN, qscR,
      mvaT, and rsmA) regulatory genes at either early or late phases of growth.
      However, with the exception of PAODeltavfr, we detected comparable levels of
      lasI/lasR expression in PAO1 and PAO1 mutants defective in these regulatory
      genes. At late stationary phase, serum failed to enhance lasI/lasR expression in
      PAODeltavfr. These results suggest that depending on the phase of growth, serum
      differentially influenced the expression of P. aeruginosa QS and QS-controlled
      virulence genes. In late phase, serum enhanced the expression of las genes
      through vfr.

PMID- 24436167
TI  - Survival from teenage and young adult cancer in Northern England, 1968-2008.
AB  - BACKGROUND: Although cancer is relatively rare in teenagers and young adults
      (TYAs) aged 15-24 years, it is a major cause of death in this age group. This
      study investigated survival trends in TYA cancer diagnosed in Northern England,
      1968-2008. METHODS: Five-year survival was analyzed using Kaplan-Meier estimation
      for four successive time periods. Cox regression analysis was used to investigate
      associations with demographic factors. RESULTS: The study included 2,987 cases
      (1,634 males, 1,353 females). Five-year survival for all patients with cancer
      improved greatly from 46% in 1968-1977 to 84% in 1998-2008 (P < 0.001), for
      patients with leukemia from 2% to 71% (P < 0.001), lymphoma from 66% to 86% (P <
      0.001), central nervous system tumors from 53% to 84% (P < 0.001), bone tumors
      from 29% to 72% (P < 0.001), germ cell tumors from 39% to 94% (P < 0.001),
      melanoma and skin cancer from 64% to 100% (P < 0.001), and carcinomas from 48% to
      80% (P < 0.001). Cox analysis showed that for all patients with cancer, survival
      was better for females than males (HR = 0.83; 95% CI 0.74-0.94, P < 0.001), for
      patients aged 20-24 years compared with those aged 15-19 years (HR = 0.84; 95% CI
      0.75-0.94, P = 0.002), but survival was worse for patients who resided in more
      deprived areas (HR = 1.06; 95% CI 1.01-1.11, P = 0.025). CONCLUSION: There have
      been large improvements in TYA cancer survival in Northern England over the last
      four decades. Future work should determine factors that could lead to even better
      survival, including possible links with delayed diagnosis.

PMID- 24436169
TI  - Musculoskeletal and neurological injuries associated with work organization among
      immigrant Latino women manual workers in North Carolina.
AB  - BACKGROUND: This analysis examines the associations of work organization
      attributes among Latino women in manual occupations with musculoskeletal and
      neurological injuries. METHODS: Participants included 234 women in western North
      Carolina. Outcome measures included epicondylitis, rotator cuff syndrome, back
      pain, and carpal tunnel syndrome. Independent measures included indicators of job
      demand, job control, and job support, as well as personal characteristics.
      RESULTS: Latina workers commonly experienced epicondylitis, rotator cuff
      syndrome, back pain, and CTS. Awkward posture and decision latitude were
      associated with epicondylitis. Rotator cuff syndrome was associated with awkward
      posture and psychological demand. Awkward posture and psychological demand, and
      decreased skill variety and job control were related to CTS. CONCLUSIONS: Work
      organization factors are potentially important for musculoskeletal and
      neurological injury among vulnerable workers. Research is required to understand
      the associations of work and health outcomes of these women. Policy initiatives
      need to consider how work organization affects health.

PMID- 24436168
TI  - Effects of short-term exposure to inhalable particulate matter on DNA methylation
      of tandem repeats.
AB  - There is compelling evidence that particulate matter (PM) increases lung cancer
      risk by triggering systemic inflammation, and leukocyte DNA hypomethylation.
      However, previous investigations focused on repeated element sequences from LINE
      1 and Alu families. Tandem repeats, which display a greater propensity to mutate,
      and are often hypomethylated in cancer patients, have never been investigated in
      individuals exposed to PM. We measured methylation of three tandem repeats
      (SATalpha, NBL2, and D4Z4) by polymerase chain reaction-pyrosequencing on blood
      samples from truck drivers and office workers (60 per group) in Beijing, China.
      We used lightweight monitors to measure personal PM2.5 (PM with aerodynamic
      diameter <=2.5 um) and elemental carbon (a tracer of PM from vehicular traffic).
      Ambient PM10 data were obtained from air quality measuring stations. Overall, an
      interquartile increase in personal PM2.5 and ambient PM10 levels was associated
      with a significant covariate-adjusted decrease in SATalpha methylation (-1.35% 5
      methyl cytosine [5mC], P = 0.01; and -1.33%5mC; P = 0.01, respectively). Effects
      from personal PM2.5 and ambient PM10 on SATalpha methylation were stronger in
      truck drivers (-2.34%5mC, P = 0.02; -1.44%5mC, P = 0.06) than office workers (
      0.95%5mC, P = 0.26; -1.25%5mC, P = 0.12, respectively). Ambient PM10 was
      negatively correlated with NBL2 methylation in truck drivers (-1.38%5mC, P =
      0.03) but not in office workers (1.04%5mC, P = 0.13). Our result suggests that PM
      exposure is associated with hypomethylation of selected tandem repeats. Measuring
      tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify
      individuals with biological effects and potential cancer risk from PM exposure.

PMID- 24436173
TI  - Precisely controlled polymer architectures.

PMID- 24436174
TI  - Intra-chain photodimerization of pendant anthracene units as an efficient route
      to single-chain nanoparticle fabrication.
AB  - An efficient route to architecturally defined, sub-20 nm soft nanoparticles
      fabricated from single polymer chains via intramolecular photodimerization of
      pendant anthracene units is presented. Photodimerization is confirmed by the
      disappearance of the characteristic anthracene pi-pi* absorption peak at ~ 360 nm
      measured by UV-vis spectroscopy. Size exclusion chromatography (SEC) with UV,
      multi-angle light scattering (MALS), and viscometric detection confirms that as
      photodimers form, the chains fold to form nanoparticles, demonstrated by shifts
      in the SEC traces to longer retention times as a function of increased
      irradiation time. These shifts indicate a reduction in hydrodynamic radius,
      corroborated and quantified by viscometric data. MALS detector traces reveal the
      presence of a small amount of chain-chain coupling during this process, but
      confirm that this is primarily a single-chain phenomenon. Electron microscopy
      provides visual confirmation of nanoparticle formation.

PMID- 24436170
TI  - The complex interplay of iron, biofilm formation, and mucoidy affecting
      antimicrobial resistance of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that
      is refractory to a variety of current antimicrobial therapeutic regimens.
      Complicating treatment for such infections is the ability of P. aeruginosa to
      form biofilms, as well as several innate and acquired resistance mechanisms.
      Previous studies suggest iron plays a role in resistance to antimicrobial
      therapy, including the efficacy of an FDA-approved iron chelator, deferasirox
      (DSX), or Gallium, an iron analog, in potentiating antibiotic-dependent killing
      of P. aeruginosa biofilms. Here, we show that iron-replete conditions enhance
      resistance of P. aeruginosa nonbiofilm growth against tobramycin and tigecycline.
      Interestingly, the mechanism of iron-enhanced resistance to each of these
      antibiotics is distinct. Whereas pyoverdine-mediated iron uptake is important for
      optimal resistance to tigecycline, it does not enhance tobramycin resistance. In
      contrast, heme supplementation results in increased tobramycin resistance, while
      having no significant effect on tigecycline resistance. Thus, nonsiderophore
      bound iron plays an important role in resistance to tobramycin, while pyoverdine
      increases the ability of P. aeruginosa to resist tigecycline treatment. Lastly,
      we show that iron increases the minimal concentration of tobramycin, but not
      tigecycline, required to eradicate P. aeruginosa biofilms. Moreover, iron
      depletion blocks the previous observed induction of biofilm formation by
      subinhibitory concentrations of tobramycin, suggesting iron and tobramycin signal
      through overlapping regulatory pathways to affect biofilm formation. These data
      further support the role of iron in P. aeruginosa antibiotic resistance,
      providing yet another compelling case for targeting iron acquisition for future
      antimicrobial drug development.

PMID- 24436177
TI  - Role of the second-trimester 'genetic sonogram' for Down syndrome screen in the
      era of first-trimester screening and noninvasive prenatal testing.
AB  - Ultrasonography for the screening of Down syndrome was first introduced about 25
      years ago. Different combinations of markers detectable at second-trimester
      ultrasonography have been proposed under the banner of 'genetic sonogram'. In
      recent years, several developments in first-trimester screening and the recent
      introduction of noninvasive prenatal testing for aneuploidy screening have had
      important implications for the prevalence of these conditions in the second
      trimester and the screening performance of a genetic sonogram. Several second
      trimester sonographic markers for Down syndrome have been reported; meta-analysis
      has shown that the most powerful predictors are mild ventriculomegaly, increased
      nuchal fold, hyperechoic bowel, and absent or hypoplastic nasal bone. Whereas use
      of individual markers should be discouraged and scoring systems of multiple
      markers are now obsolete, use of combined likelihood ratio and logistic
      regression analysis formulae provides better accuracy. However, there is
      significant heterogeneity in results among studies. Despite such limitations, the
      genetic sonogram will continue to have a place in prenatal screening,
      particularly in twin and higher-order multiple pregnancies, in countries with
      limited access to the most recent genetic screening tests, in cases with
      borderline results at maternal serum screening tests, and as noninvasive
      supplementary test for high-risk women reluctant to undergo invasive diagnostic
      testing.

PMID- 24436178
TI  - Decreased aorto-septal angle may contribute to left ventricular diastolic
      dysfunction in healthy subjects.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction is often observed in
      healthy older subjects without structural heart disease, although its exact
      mechanisms have not been established. A decrease in the aorto-septal angle (ASA),
      an alteration of LV shape due to aortic elongation, is also frequently seen in
      elderly subjects. The objective of this study was to evaluate whether it can
      contribute to LV diastolic dysfunction in healthy subjects. METHODS:
      Echocardiography was performed in 77 healthy subjects (42 men, mean age 43.2 +/-
      13.8 years) to measure the ASA, early diastolic transmitral flow velocity (E),
      isovolumic relaxation time (IRT), and early diastolic mitral annular velocity
      (e'). The LV peak early diastolic longitudinal strain rate (GSRE ) was measured
      using a two-dimensional speckle tracking imaging technique. RESULTS: ASA was
      significantly correlated with E (r = 0.54, p < 0.001), IRT (r = -0.41, p <
      0.001), e' (r = 0.57, p < 0.001), and GSRE (r = 0.63, p < 0.001) and shown by
      stepwise multivariate analysis to be the strongest independent determinant of E,
      IRT, and GSRE , and one of the independent determinants of e'. CONCLUSIONS: The
      alteration of LV shape associated with reduced ASA may be one of the causes of LV
      diastolic dysfunction independently of age in otherwise healthy subjects.

PMID- 24436179
TI  - National-level differences in the adoption of environmental health technologies:
      a cross-border comparison from Benin and Togo.
AB  - Environmental health problems such as malaria, respiratory infections, diarrhoea
      and malnutrition pose very high burdens on the poor rural people in much of the
      tropics. Recent research on key interventions-the adoption and use of relatively
      cheap and effective environmental health technologies-has focused primarily on
      the influence of demand-side household-level drivers. Relatively few studies of
      the promotion and use of these technologies have considered the role of
      contextual factors such as governance, the enabling environment and national
      policies because of the challenges of cross-country comparisons. We exploit a
      natural experimental setting by comparing household adoption across the Benin
      Togo national border that splits the Tamberma Valley in West Africa. Households
      across the border share the same culture, ethnicity, weather, physiographic
      features, livelihoods and infrastructure; however, they are located in countries
      at virtually opposite ends of the institutional spectrum of democratic elections,
      voice and accountability, effective governance and corruption. Binary choice
      models and rigorous non-parametric matching estimators confirm that households in
      Benin are more likely than households in Togo to plant soybeans, build improved
      cookstoves and purchase mosquito nets, ceteris paribus. Although we cannot
      identify the exact mechanism for the large and significant national-level
      differences in technology adoption, our findings suggest that contextual
      institutional factors can be more important than household characteristics for
      technology adoption. 

PMID- 24436180
TI  - Shear reversible cell/microsphere aggregate as an injectable for tissue
      regeneration.
AB  - Injectable delivery systems have been widely used in tissue engineering as they
      can deliver cells into the body in a minimally invasive manner. In this study, it
      is hypothesized that microspheres with a similar size of cells could effectively
      form a shear reversible aggregate in the presence of cells and the aggregate
      could be useful to engineer tissues. Alginate microspheres are prepared by an
      emulsion method, followed by modification with a peptide containing the arginine
      glycine-aspartic acid (RGD) sequence. RGD-modified alginate microspheres form an
      aggregate in the presence of chondrocytes, and the aggregation behavior is shear
      reversible. This cell/microsphere aggregate is useful to deliver chondrocytes
      into an animal model using a syringe, and effectively regenerates cartilage
      tissues in vivo. 

PMID- 24436181
TI  - A promiscuous intermediate underlies the evolution of LEAFY DNA binding
      specificity.
AB  - Transcription factors (TFs) are key players in evolution. Changes affecting their
      function can yield novel life forms but may also have deleterious effects.
      Consequently, gene duplication events that release one gene copy from selective
      pressure are thought to be the common mechanism by which TFs acquire new
      activities. Here, we show that LEAFY, a major regulator of flower development and
      cell division in land plants, underwent changes to its DNA binding specificity,
      even though plant genomes generally contain a single copy of the LEAFY gene. We
      examined how these changes occurred at the structural level and identify an
      intermediate LEAFY form in hornworts that appears to adopt all different
      specificities. This promiscuous intermediate could have smoothed the evolutionary
      transitions, thereby allowing LEAFY to evolve new binding specificities while
      remaining a single-copy gene. 

PMID- 24436182
TI  - Lost in transition: start-up of glycolysis yields subpopulations of nongrowing
      cells.
AB  - Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic
      changes in the abundance of glucose can undergo growth arrest. We show that this
      failure is caused by imbalanced reactions in glycolysis, the essential pathway in
      energy metabolism in most organisms. The imbalance arises largely from the
      fundamental design of glycolysis, making this state of glycolysis a generic risk.
      Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous,
      nongenetic metabolic variability among individual cells determines which state is
      reached and, consequently, which cells survive. Transient ATP (adenosine 5'
      triphosphate) hydrolysis through futile cycling reduces the probability of
      reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis
      and indicate that cell fate can be determined by heterogeneity purely at the
      metabolic level. 

PMID- 24436183
TI  - Discovery of a three-dimensional topological Dirac semimetal, Na3Bi.
AB  - Three-dimensional (3D) topological Dirac semimetals (TDSs) represent an unusual
      state of quantum matter that can be viewed as "3D graphene." In contrast to 2D
      Dirac fermions in graphene or on the surface of 3D topological insulators, TDSs
      possess 3D Dirac fermions in the bulk. By investigating the electronic structure
      of Na3Bi with angle-resolved photoemission spectroscopy, we detected 3D Dirac
      fermions with linear dispersions along all momentum directions. Furthermore, we
      demonstrated the robustness of 3D Dirac fermions in Na3Bi against in situ surface
      doping. Our results establish Na3Bi as a model system for 3D TDSs, which can
      serve as an ideal platform for the systematic study of quantum phase transitions
      between rich topological quantum states. 

PMID- 24436184
TI  - Rapid soil production and weathering in the Southern Alps, New Zealand.
AB  - Evaluating conflicting theories about the influence of mountains on carbon
      dioxide cycling and climate requires understanding weathering fluxes from
      tectonically uplifting landscapes. The lack of soil production and weathering
      rate measurements in Earth's most rapidly uplifting mountains has made it
      difficult to determine whether weathering rates increase or decline in response
      to rapid erosion. Beryllium-10 concentrations in soils from the western Southern
      Alps, New Zealand, demonstrate that soil is produced from bedrock more rapidly
      than previously recognized, at rates up to 2.5 millimeters per year. Weathering
      intensity data further indicate that soil chemical denudation rates increase
      proportionally with erosion rates. These high weathering rates support the view
      that mountains play a key role in global-scale chemical weathering and thus have
      potentially important implications for the global carbon cycle. 

PMID- 24436185
TI  - Low core-mantle boundary temperature inferred from the solidus of pyrolite.
AB  - The melting temperature of Earth's mantle provides key constraints on the thermal
      structures of both the mantle and the core. Through high-pressure experiments and
      three-dimensional x-ray microtomographic imaging, we showed that the solidus
      temperature of a primitive (pyrolitic) mantle is as low as 3570 +/- 200 kelvin at
      pressures expected near the boundary between the mantle and the outer core.
      Because the lowermost mantle is not globally molten, this provides an upper bound
      of the temperature at the core-mantle boundary (T(CMB)). Such remarkably low
      T(CMB) implies that the post-perovskite phase is present in wide areas of the
      lowermost mantle. The low T(CMB) also requires that the melting temperature of
      the outer core is depressed largely by impurities such as hydrogen.

PMID- 24436187
TI  - Construction and evaluation of a switch-tuned (13) C - (1) H birdcage
      radiofrequency coil for imaging the metabolism of hyperpolarized (13) C-enriched
      compounds.
AB  - PURPOSE: To construct a switch-tuned (13) C - (1) H birdcage radiofrequency (RF)
      coil system capable of metabolic imaging of hyperpolarized (13) C-enriched
      metabolic probes for co-registration with MRI morphology using protons. MATERIALS
      AND METHODS: The switch-tuned coil was constructed using PIN diodes for rapid
      switching of the resonant frequency of the coil. Identical, single-tuned, (1) H
      and (13) C birdcage RF coils have also been constructed for comparison of imaging
      performance. A (13) C receive-only surface RF coil has been integrated with the
      switch-tuned coil for transmit-only, receive-only operation (TORO) to increase
      local (13) C signal for improved signal-to-noise ratio (SNR). RESULTS: The SNR
      achieved with the switch-tuned coil in transmit/receive mode was 87% that of the
      single-tuned (1) H coil. For (13) C imaging, the SNR for the switch-tuned coil
      was 55% that of the single-tuned (13) C coil. TORO operation of the switch-tuned
      coil with the surface coil increased SNR for by a factor of 4.2 over
      transmit/receive operation of the switch-tuned coil alone. CONCLUSION: A surface
      coil can be integrated with a switch-tuned (13) C - (1) H coil for (13) C TORO
      operation producing improved SNR. In vivo metabolic imaging of [1-(13) C]pyruvate
      in a rat model of glioma is demonstrated using TORO operation, which is co
      registered with (1) H-imaged anatomy.

PMID- 24436186
TI  - Distribution of ESCRT machinery at HIV assembly sites reveals virus scaffolding
      of ESCRT subunits.
AB  - The human immunodeficiency virus (HIV) hijacks the endosomal sorting complexes
      required for transport (ESCRT) to mediate virus release from infected cells. The
      nanoscale organization of ESCRT machinery necessary for mediating viral
      abscission is unclear. Here, we applied three-dimensional superresolution
      microscopy and correlative electron microscopy to delineate the organization of
      ESCRT components at HIV assembly sites. We observed ESCRT subunits localized
      within the head of budding virions and released particles, with head-localized
      levels of CHMP2A decreasing relative to Tsg101 and CHMP4B upon virus abscission.
      Thus, the driving force for HIV release may derive from initial scaffolding of
      ESCRT subunits within the viral bud interior followed by plasma membrane
      association and selective remodeling of ESCRT subunits. 

PMID- 24436188
TI  - The impact of anemia on microsurgical breast reconstruction complications and
      outcomes.
AB  - INTRODUCTION: Appropriate and adequate blood flow and oxygen delivery to a free
      flap is paramount to viability and success. We present a comprehensive
      examination of perioperative anemia, determining its prevalence and effect on
      complications and outcomes in autologous breast reconstruction. METHODS: We
      analyzed all autologous free flap breast reconstruction at the Hospital of the
      University of Pennsylvania from 2005 to 2011 with regards to anemia (hemoglobin
      (Hgb) <12 g dL(-1) ). Anemic patients were compared to those with Hgb > 12 g dL(
      1) at preoperative and postoperative timepoints. Complications were analyzed
      relative to HgB levels and the incidence of anemia. Subgroups were analyzed based
      on worsening degrees of anemia. RESULTS: Overall, 839 patients were included in
      the analysis with an 18.3% incidence of preoperative anemia. No significant
      differences were noted in outcomes of these patients relative to their anemic
      state, although a higher percent did receive a blood transfusion (18% of anemic
      patients vs. 6% of nonanemic patients, P < 0.0001). There was a significant
      incidence of postoperative anemia (93.4%). A subgroup analysis demonstrated that
      worsening postoperative anemia was significantly related to preoperative HgB (P <
      0.0001), bilateral cases (P < 0.0001), immediate reconstructions (P < 0.0001),
      increased estimated blood loss (P = 0.0001), and higher rates of intraoperative
      fluid administration (P = 0.025). A higher incidence of medical complications was
      observed in cohorts with HgB < 10 (P = 0.018). CONCLUSIONS: Anemia affects a
      significant portion of breast reconstruction patients. While preoperative anemia
      is not associated with increased risk of flap related complications,
      postoperative anemia may be associated with an increased risk of medical
      complications.

PMID- 24436189
TI  - Digoxin-induced reversible dysfunction of the cone photoreceptors in monkeys.
AB  - PURPOSE: To investigate functional alteration of the retina induced by digoxin in
      monkeys. METHODS: Digoxin was intravenously administered to cynomolgus monkeys
      and standard full-field electroretinograms (ERGs) were serially recorded. In
      other digoxin-treated monkeys, the rod and cone a-waves to high-intensity flashes
      were obtained and analyzed by the a-wave fitting model (a-wave analysis). The
      following responses were also recorded: dark- and light-adapted responses to
      flashes of different intensities (dark- and light-adapted luminance responses),
      photopic ERG elicited by long-duration stimulus (ON-OFF response), and the
      photopic negative response (PhNR). RESULTS: Delayed b-wave was observed in all
      responses of the standard full-field ERGs; amplitude of the b-wave was increased
      in the rod response, but was decreased in the single-flash cone response and the
      30-Hz flicker. These changes recovered gradually after elimination of digoxin
      from the blood. Digoxin enhanced and delayed the b-wave in the dark-adapted
      luminance-response analysis regardless of stimulus intensity. In the light
      adapted luminance-response analysis, digoxin attenuated the a- and b-waves only
      at high and middle stimulus intensity, respectively. The a-wave analysis revealed
      selective decrease in the maximum response parameter (Rmax) in the cone a-wave.
      Both the b- and d-waves of the ON-OFF response were delayed. CONCLUSIONS: The
      selectively reduced Rmax in the cone a-wave indicated dysfunction of the cone
      photoreceptors in digoxin-treated monkeys. Meanwhile, the enhanced and delayed
      rod response suggested alteration of retinal components other than the cone
      photoreceptors. These results may contribute to the understanding of digoxin
      induced visual disturbances in humans. It is suggested that the cone function is
      markedly, but not exclusively, affected in the retina of such patients.

PMID- 24436191
TI  - Aberrant expression of long noncoding RNAs in early diabetic retinopathy.
AB  - PURPOSE: Long noncoding RNAs (lncRNAs) are broadly classified as transcripts
      longer than 200 nucleotides. lncRNA-mediated biology has been implicated in a
      variety of cellular processes and human diseases. Diabetic retinopathy (DR) is
      one of the leading causes of blindness. However, little is known about the role
      of lncRNAs in DR The goal of this study aimed to identify lncRNAs involved in
      early DR and characterize their roles in DR pathogenesis. METHODS: We established
      a mouse model of streptozotocin (STZ)-induced diabetes, and performed lncRNA
      expression profiling of retinas using microarray analysis. Based on the Pearson
      correlation analysis, an lncRNA/mRNA coexpression network was constructed. Gene
      ontology (GO) enrichment and KEGG analysis of lncRNAs-coexpressed mRNAs was
      conducted to identify the related biological modules and pathologic pathways.
      Real-time PCR was conducted to detect the expression pattern of lncRNA in the
      clinical samples and the RF/6A cell model of hyperglycemia. RESULTS:
      Approximately 303 lncRNAs were aberrantly expressed in the retinas of early DR,
      including 214 downregulated lncRNAs and 89 upregulated lncRNAs. GO analysis
      indicated that these lncRNAs-coexpressed mRNAs were targeted to eye development
      process (ontology: biological process), integral to membrane (ontology: cellular
      component), and structural molecule activity (ontology: molecular function).
      Pathway analysis indicated that lncRNAs-coexpressed mRNAs were mostly enriched in
      axon guidance signaling pathway. In addition, MALAT1, a conserved lncRNA, was
      significantly upregulated in an RF/6A cell model of hyperglycemia, in the aqueous
      humor samples, and in fibrovascular membranes of diabetic patients. CONCLUSIONS:
      lncRNAs are involved in the pathogenesis of DR through the modulation of multiple
      pathogenetic pathways. MALAT1, a conserved lncRNA, may become a potential
      therapeutic target for the prognosis, diagnosis, and treatment of DR.

PMID- 24436190
TI  - Static blood flow autoregulation in the optic nerve head in normal and
      experimental glaucoma.
AB  - PURPOSE: To characterize the static blood flow autoregulation in the optic nerve
      head (ONH), and to investigate its role in hemodynamic changes in experimental
      glaucoma (EG). METHODS: Unilateral elevation of intraocular pressure (IOP) was
      induced in 15 adult rhesus macaques by laser treatment to the trabecular
      meshwork. Prior to and after laser treatment, retinal nerve fiber layer thickness
      (RNFLT) was assessed, biweekly, by spectral-domain optical coherence tomography.
      Optic nerve head static autoregulation was assessed by determining the percentage
      blood flow (BF) change after the IOP was acutely increased from 10 to 30, 40, or
      50 mm Hg manometrically, utilizing a laser speckle flowgraphy device. RESULTS:
      Postlaser IOP (measured during average 7.7 +/- 2.6 months) was 20.2 +/- 5.9 mm Hg
      in EG eyes and 12.3 +/- 2.6 mm Hg in control eyes (P < 0.0001). Retinal nerve
      fiber layer thickness was reduced by 33 +/- 22% of the baseline values (P <
      0.001) on average in EG eyes and by 0.4 +/- 2.3% in control eyes (P > 0.05). The
      ONH BF remained at a constant level within a range of ocular perfusion pressure
      (OPP), 41 mm Hg and above. The autoregulation curves, created by all 723 tests in
      control and 352 tests in EG, were not significantly different (P = 0.71).
      CONCLUSIONS: Optic nerve head BF in normal nonhuman primate (NHP) eyes is
      effectively regulated within a range of OPP approximately 41 mm Hg and above.
      Chronic IOP elevation causes no remarkable change to the static autoregulation
      within the ONH of EG eyes.

PMID- 24436192
TI  - Differences between niche cells and limbal stromal cells in maintenance of
      corneal limbal stem cells.
AB  - PURPOSE: To investigate the differing characteristics of limbal niche cells
      (LNCs) and limbal stromal cells (LSCs) in the maintenance of limbal epithelial
      stem/progenitor cells in the cornea. METHODS: Limbal niche cells were obtained
      from direct dissection of the human corneal limbus, and LSCs were obtained from
      explant cultures of limbal stromal tissues under the same culture conditions. The
      resulting cultures were examined for their ability to support the growth of
      limbal stem/progenitor cells in colony-forming capacity, stratified epithelial
      cell sheet formation, maintenance of limbal epithelial stem/progenitor cell
      characteristics, and gene expression levels of factors that supported the limbal
      epithelial stem/progenitor cells. RESULTS: The colony-forming efficiency of
      limbal epithelial stem/progenitor cells in the LNC group (6.57 +/- 1.54%) was
      significantly higher than that in the LSC group (1.43 +/- 0.47%). The epithelial
      cell sheets in the LNC group stratified into four or five layers compared with
      two or three stratified layers in the LSC group. Staining of both the colonies
      and the epithelial cell sheets in the LNC group showed a higher intensity of the
      limbal stem cell marker DeltaNp63 than in the LSC group. Moreover, reverse
      transcription polymerase chain reaction analysis revealed that compared with the
      common expression of EGF and so on, the LNCs showed a higher expression level of
      E-cadherin and a lower expression level of neurotrophin-3 (NT3) than the LSCs.
      CONCLUSIONS: LNCs have a different role compared to LSCs in their ability to
      support epithelial stem/progenitor cells and epithelial cellular sheet formation.

PMID- 24436193
TI  - Enrichment of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)-positive
      macrophages around blood vessels in the normal human sclera.
AB  - PURPOSE: To investigate whether the normal adult human sclera contains lymphatic
      vessels and to study their relation to immune cells and blood vessel anatomy.
      METHODS: Scleral tissue probes from 35 adult human donor bulbi were analyzed by
      immunohistochemistry and confocal microscopy for blood vessels (CD31+), lymphatic
      vessels (lymphatic vessel endothelial hyaluronan receptor 1 [LYVE1]+,
      podoplanin+), and macrophages (CD68+) at 12 locations (anterior, equatorial, and
      posterior at 3, 6, 9, and 12 o'clock positions of the eye) in all three scleral
      layers (episclera, stroma, and lamina fusca). Approval for scientific examination
      was obtained. RESULTS: CD31+ blood vessels were detectable in the human sclera,
      where the percentage area covered by CD31+ blood vessels was highest in the
      anterior episclera, followed by equatorial and posterior episclera, and was
      lowest in the scleral stroma (regardless of location). LYVE1+ podoplanin+
      lymphatic vessels were not detectable in any location investigated, although
      there was a high number of LYVE1+ CD68+ macrophages. These macrophages were
      concentrated around blood vessels. In contrast, in the episclera, the number of
      detected LYVE1+ CD68+ macrophages was comparable in all locations; within the
      stroma, their number increased toward the posterior part of the eye. CONCLUSIONS:
      The adult sclera contains blood vessels but lacks, as revealed by
      immunohistochemistry and confocal microscopy, true lymphatic vessels. LYVE1+
      CD68+ macrophages are located adjacent to the longitudinal axis of blood vessels.
      The function of these cells needs further investigation, but could be a next step
      toward a better understanding of pathological disorders such as inflammation,
      tumor, trauma, or glaucoma.

PMID- 24436194
TI  - Lipochitin oligosaccharides immobilized through oximes in glycan microarrays bind
      LysM proteins.
AB  - Glycan microarrays have emerged as novel tools to study carbohydrate-protein
      interactions. Here we describe the preparation of a covalent microarray with
      lipochitin oligosaccharides and its use in studying proteins containing LysM
      domains. The glycan microarray was assembled from glycoconjugates that were
      synthesized by using recently developed bifunctional chemoselective aminooxy
      reagents without the need for transient carbohydrate protecting groups. We
      describe for the first time the preparation of a covalent microarray with
      lipochitin oligosaccharides and its use for studying proteins containing LysM
      domains. Lipochitin oligosaccharides (also referred to as Nod factors) were
      isolated from bacterial strains or chemoenzymatically synthesized. The glycan
      microarray also included peptidoglycan-related compounds, as well as chitin
      oligosaccharides of different lengths. In total, 30 ligands were treated with the
      aminooxy linker molecule. The identity of the glycoconjugates was verified by
      mass spectrometry, and they were then immobilized on the array. The presence of
      the glycoconjugates on the array surface was confirmed by use of lectins and
      human sera (IgG binding). The functionality of our array was tested with a
      bacterial LysM domain-containing protein, autolysin p60, which is known to act on
      the bacterial cell wall peptidoglycan. P60 showed specific binding to Nod factors
      and to chitin oligosaccharides. Increasing affinity was observed with increasing
      chitin oligomer length.

PMID- 24436195
TI  - Protease production by Staphylococcus epidermidis and its effect on
      Staphylococcus aureus biofilms.
AB  - Due to the resistance of Staphylococcus aureus to several antibiotics, treatment
      of S. aureus infections is often difficult. As an alternative to conventional
      antibiotics, the field of bacterial interference is investigated. Staphylococcus
      epidermidis produces a serine protease (Esp) which inhibits S. aureus biofilm
      formation and which degrades S. aureus biofilms. In this study, we investigated
      the protease production of 114 S. epidermidis isolates, obtained from biofilms on
      endotracheal tubes (ET). Most of the S. epidermidis isolates secreted a mixture
      of serine, cysteine and metalloproteases. We found a link between high protease
      production by S. epidermidis and the absence of S. aureus in ET biofilms obtained
      from the same patient. Treating S. aureus biofilms with the supernatant (SN) of
      the most active protease producing S. epidermidis isolates resulted in a
      significant biomass decrease compared to untreated controls, while the number of
      metabolically active cells was not affected. The effect on the biofilm biomass
      was mainly due to serine proteases. Staphylococcus aureus biofilms treated with
      the SN of protease producing S. epidermidis were thinner with almost no
      extracellular matrix. An increased survival of Caenorhabditis elegans, infected
      with S. aureus Mu50, was observed when the SN of protease positive S. epidermidis
      was added.

PMID- 24436196
TI  - Time in hemodialysis modulates the levels of genetic damage in hemodialysis
      patients.
AB  - It is assumed that hemodialysis treatment can diminish the levels of genetic
      damage in circulating lymphocytes by cleaning the blood of uremic toxins that
      cause oxidative stress. However, the hemodialysis process by itself may also
      induce genomic damage by producing reactive oxygen species (ROS). We conducted a
      follow-up study in a group of 70 hemodialysis patients followed for a mean time
      of 15 months. We investigated the effect of exposure time in hemodialysis on the
      levels of genetic damage in peripheral blood lymphocytes using the micronucleus
      assay. In addition, genetic damage after in vitro irradiation with 0.5 Gy was
      also analyzed to evaluate changes in radiosensitivity. Our results showed that,
      at the end of the study, there was a decrease in both the basal levels of genetic
      damage (9.9 +/- 1.0 vs. 7.6 +/- 0.7) and radiosensitivity values (38.5 +/- 3.0
      vs. 27.6 +/- 2.4). We conclude that hemodialysis procedures may act as an
      ameliorating factor reducing the genetic damage present in chronic kidney disease
      patients.

PMID- 24436197
TI  - Species concept in primates.
AB  - The way we view the Species category in Primates, as in other animals, especially
      other vertebrates, has been going through a revolution over the past 20 years or
      so. Much is wrong with the idea that we can define species according to whether
      or not they are "reproductively isolated": this concept, the so-called Biological
      Species Concept, has never offered any guidelines in the case of allopatric
      populations; this has now been shown to be simply wrong. Although other ways of
      looking at species - the Evolutionary, Recognition, Cohesion and Genetic Species
      Concepts - have all provided particular insights, the only proposal to offer a
      repeatable, falsifiable definition of species is the Phylogenetic Species
      Concept. This has been criticised for increasing the number of species to be
      recognised, although it is not clear why this should be a problem: indeed, it
      tells us that the world is far richer in biodiversity than we had conceived.

PMID- 24436198
TI  - Birth timing and behavioral responsiveness predict individual differences in the
      mother-infant relationship and infant behavior during weaning and maternal
      breeding.
AB  - There is a great deal of variability in mother-infant interactions and infant
      behavior across the first year of life in rhesus monkeys. The current article has
      two specific aims: (1) to determine if birth timing predicts variability in the
      mother-infant relationship and infant behavior during weaning and maternal
      breeding, and (2) to identify predictors of infant behavior during a period of
      acute challenge, maternal breeding. Forty-one mother-infant pairs were observed
      during weaning when infants were 4.5 months old, and 33 were followed through
      maternal breeding. Subjective ratings of 16 adjectives reflecting qualities of
      maternal attitude, mother-infant interactions, and infant attitude were factor
      analyzed to construct factors relating to the mother-infant relationship (Relaxed
      and Aggressive) and infant behavior (Positive Engagement and Distress). During
      weaning, late born infants were more Positively Engaged than peak born infants
      (ANOVA, P < 0.05); however, birth timing did not affect the mother-infant
      relationship factors Relaxed and Aggressive or the infant attitude factor
      Distress. During maternal breeding, early born infants had less Relaxed
      relationships with their mothers than peak or late born infants, higher Positive
      Engagement scores than peak or late born infants, and tended to have higher
      Distress scores than peak born infants (repeated-measures ANOVA, P < 0.05). In
      addition, Distress scores were higher during maternal breeding than during the
      pre- and postbreeding phases. Finally, multiple regression (P < 0.05) indicated
      that while infant behavioral responsiveness predicted infant Positive Engagement
      during the acute challenge of maternal breeding, qualities of the mother-infant
      relationship predicted infant Distress. These data suggest that birth timing
      influences the patterns of mother-infant interactions during weaning and maternal
      breeding. Additionally, infant behavioral responsiveness and mother-infant
      relationship quality impact infant social engagement and affect expression,
      respectively.

PMID- 24436199
TI  - A large-scale SNP-based genomic admixture analysis of the captive rhesus macaque
      colony at the California National Primate Research Center.
AB  - Some breeding facilities in the United States have crossbred Chinese and Indian
      rhesus macaque (Macaca mulatta) founders either purposefully or inadvertently.
      Genetic variation that reflects geographic origins among research subjects has
      the potential to influence experimental outcomes. The use of animals from
      different geographic regions, their hybrids, and animals of varying degrees of
      kinship in an experiment can obscure treatment effects under study because high
      interanimal genetic variance can increase phenotypic variance among the research
      subjects. The intent of this study, based on a broad genomic analysis of 2,808
      single nucleotide polymorphisms (SNPs), is to ensure that only animals estimated
      to be of pure Indian or Chinese ancestry, based on both demographic and genetic
      information, are used as sources of infants for derivation and expansion of the
      California National Primate Research Center's (CNPRC) super-Specific Pathogen
      Free (SSPF) rhesus macaque colony. Studies of short tandem repeats (STRs) in
      Indian and Chinese rhesus macaques have reported that heterozygosity of STRs is
      higher in Chinese rhesus macaques than in Indian rhesus macaques. The present
      study shows that heterozygosity of SNPs is actually higher in Indian than in
      Chinese rhesus macaques and that the Chinese SSPF rhesus macaque colony is far
      less differentiated from their founders compared to the Indian-origin animals.
      The results also reveal no evidence of recent gene flow from long-tailed and pig
      tailed macaques into the source populations of the SSPF rhesus macaques. This
      study indicates that many of the long-tailed macaques held in the CNPRC are
      closely related individuals. Most polymorphisms shared among the captive rhesus,
      long-tailed, and pig-tailed macaques likely predate the divergence among these
      groups.

PMID- 24436200
TI  - Combining ring-opening metathesis polymerization and thiol-ene coupling
      chemistries: facile access to novel functional linear and nonlinear
      macromolecules.
AB  - The aim of this article is to highlight recent examples in which two powerful
      synthetic tools, namely ring-opening metathesis polymerization (ROMP) and thiol
      ene (including the thiol-Michael variant) click chemistry have been combined to
      facilitate the preparation of novel functional materials of varying topology. 

PMID- 24436201
TI  - Doppler ultrasonographic evaluation of the radial and ulnar arteries in
      hemiparetic patients after stroke.
AB  - BACKGROUND: To evaluate blood flow of hand arteries (using Doppler
      ultrasonography) and sympathetic skin response (SSR) in patients with
      hemiparesis. METHODS: Fifty-six stroke patients (30 M, 26 F) with unilateral
      hemiparesis (age 53.5 +/- 10.8 years, mean disease duration 12.0 +/- 19.1 months)
      were included. The patients' arm and hand motor functions were assessed according
      to Brunnstrom's stages. SSR was evaluated bilaterally from median nerves at the
      wrist level. Radial and ulnar artery blood flow was measured at the wrist in the
      neutral position. RESULTS: Both radial and ulnar artery volume flow and end
      diastolic velocity, and radial artery diameter were smaller on the paretic side
      (all p < 0.0125). Radial artery resistance and pulsatility index were greater on
      the paretic side (both p < 0.0125). SSR amplitude was lower on the paretic side
      of patients with right-sided hemiparesis patients (p = 0.009). Hand Brunnstrom's
      stage was negatively correlated with nonparetic-paretic difference in radial
      artery volume flow and SSR amplitudes (all p < 0.025). CONCLUSIONS: Hand blood
      flow was lower on the paretic side and was accompanied by a similar decrease in
      SSR amplitudes in patients with right-sided hemiparesis.

PMID- 24436202
TI  - De novo small supernumerary marker chromosomes detected on 143,000 consecutive
      prenatal diagnoses: chromosomal distribution, frequencies, and characterization
      combining molecular cytogenetics approaches.
AB  - OBJECTIVE: The risk of clinical consequences in prenatal cases with de novo small
      supernumerary marker chromosomes (sSMC), often in mosaic conditions, is not easy
      to predict, which results in difficulties in genetic counseling. METHOD: In this
      study, we evaluated the frequency, the chromosomal origin, and the clinical
      indication of 104 de novo sSMC detected in a monocenter survey on the basis of
      143,000 consecutive prenatal diagnoses, and we assessed the reliability of
      molecular cytogenetics technologies for sSMC characterization. RESULTS: We
      detected a de novo sSMC frequency of 0.072%. Its incidence in advanced maternal
      age group is statistically different from that found in maternal anxiety
      indication (<35 years old). A higher prevalence of mosaicism in chorionic villi
      sampling (CVS) than in amniotic fluids was also revealed related to confined
      placental mosaicisms. The risk of confirmation in amniotic fluids of mosaics
      previously revealed at CVS was 33.3%. No uniparental disomy conditions were found
      when imprinted chromosomes were involved in the occurrence of de novo sSMC. The
      majority of de novo sSMC were acrocentric derived-chromosomes, and a
      neocentromere formation was observed in one pregnancy. CONCLUSION: Our data
      support that array comparative genomic hybridization has improved sSMC
      characterization and demonstrate its utility in supporting genetic counseling. We
      propose a workflow for de novo sSMC characterization.

PMID- 24436204
TI  - Kinetic assessment and effect on developmental physiology of a trypsin inhibitor
      from Eugenia jambolana (Jambul) seeds on Helicoverpa armigera (Hubner).
AB  - A trypsin inhibitor was purified from the seeds of Eugenia jambolana (Jambul)
      with a fold purification of 14.28 and a yield recovery of 2.8%. Electrophoretic
      analysis of E. jambolana trypsin inhibitor (EjTI) revealed a molecular weight of
      approximately 17.4 kDa on 12% denaturing polyacrylamide gel electrophoresis with
      or without reduction. EjTI exhibited high stability over a wide range of
      temperatures (4-80  degrees C for 30 min) and pH (3.0-10.0) and inhibited trypsin
      like activities of the midgut proteinases of fourth instar Helicoverpa armigera
      larvae by approximately 86%. Feeding assays containing 0.05, 0.15, and 0.45 (%
      w/w) EjTI on functionally important fourth-instar larvae indicated a dose
      dependent downfall in the larval body weight as well as on extent of survival.
      The nutritional analysis suggests that EjTI exerts toxic effects on H. armigera.
      Dixon plot analysis revealed competitive inhibition of larval midgut proteinases
      by EjTI, with an inhibition constant (Ki ) of approximately 3.1 * 10(-9) M.
      However, inhibitor kinetics using double reciprocal plots for trypsin inhibition
      demonstrated a mixed inhibition pattern. These observations suggest the potential
      of E. jambolana trypsin inhibitor protein in insect pest management.

PMID- 24436203
TI  - Effects of physical and chemical treatments on the molecular weight and
      degradation of alginate-hydroxyapatite composites.
AB  - Degradation of alginate remains a critical issue to allow predictable biological
      performance upon implantation of alginate-based materials. Therefore, the
      objective of the current study is to compare the effects of gamma-irradiation
      (dry state, 20-80 kGy), partial (1 and 4%) periodate oxidation (aqueous
      solution), and autoclaving (dry state) on the molecular weight of alginate, as
      well as the degradation behavior of alginate-based composites. The results show
      that gamma-irradiation is by far the most destructive technique characterized by
      strongly reduced molecular weights and rapid loss of composite integrity upon
      soaking in simulated body fluid. Partial periodate oxidation is less destructive
      as characterized by more moderate decreases in molecular weight, but the
      production of hydrolytically labile bonds compromises the integrity of the
      resulting composites. Autoclaving is shown to be a powerful tool to reduce the
      molecular weight of alginate in a controllable and mild manner without
      compromising the integrity of the resulting alginate-hydroxyapatite composites,
      simply by increasing the number of repetitive autoclaving cycles. 

PMID- 24436205
TI  - Genetic analyses suggest no immigration of adult females and their offspring into
      the Sonso community of chimpanzees in the Budongo Forest Reserve, Uganda.
AB  - Chimpanzees are frequently used to illustrate the relationship between sex
      differences in dispersal and sex differences in cooperation in primates and other
      group-living mammals. Male chimpanzees are highly philopatric, typically
      remaining in their natal communities for their entire lives to cooperate with
      related males in competition against less related males from other groups,
      whereas females typically disperse once at adolescence and cooperate with each
      other less frequently. However, there have been a few reports of dependent male
      offspring joining groups when their mothers transferred between communities as
      adults. Although such events are difficult to document, determining how often
      they actually occur is important for elucidating the links between philopatry,
      kinship, and cooperation in both chimpanzees and group-living animals more
      generally. Here we use genetic analyses to investigate a previous report of a
      large-scale transfer of many females and their offspring into the Sonso community
      of chimpanzees in the Budongo Forest Reserve, Uganda. Using autosomal
      microsatellite genotypes, we assigned a Sonso father to ten of the fourteen
      putative immigrants, and found that the four putative immigrants for whom we
      could not assign a Sonso father (perhaps due to incomplete sampling of all Sonso
      candidate fathers) nevertheless had Y-chromosome microsatellite haplotypes that
      were common in Sonso males but absent in males from four other chimpanzee
      communities at Budongo. These results suggest that these putative immigrant
      females and their offspring were probably actually long-term residents of Sonso
      whose identifications were delayed by their peripheral or unhabituated status.
      These results are consistent with other genetic and behavioral evidence showing
      that male between-community gene flow is exceedingly rare in east African
      chimpanzees.

PMID- 24436206
TI  - Differential methylation status of IGF2-H19 locus does not affect the fertility
      of crossbred bulls but some of the CTCF binding sites could be potentially
      important.
AB  - Associations between abnormal methylation of spermatozoan DNA with male
      infertility have been sought in recent years to identify a molecular explanation
      of differential spermatozoan function. The present work was undertaken to
      investigate the methylation profile of differentially methylated regions (DMRs)
      in the IGF2-H19 locus of Bos taurus X Bos indicus crossbred bull spermatozoa.
      Bulls having more than at least 100 insemination records over a period of 12
      years were classified into two groups of five bulls each belonging to low- and
      high-fertility groups. The IGF2 and H19 DMR sequences in B. indicus cattle were
      observed to be in absolute homology with B. taurus cattle. The DNA of crossbred
      bull spermatozoa was isolated, bisulfite treated, and amplified for specific DMR
      regions using methylation-change-specific primers. The overall degree of
      methylation at IGF2-H19 DMRs was not found to be significantly different among
      two groups of bulls. The sixth CTCF binding site (CCCTC) identified in H19 DMR,
      however, had a significant methylation difference between the high- and low
      fertility bulls. It was concluded that alteration of the methylation levels at
      IGF2-H19 DMRs might not be responsible for the fertility difference of crossbred
      bulls, although the role played by the specific CTCF binding sites at this locus,
      which could influence IGF2 expression during spermatogenesis and early embryonic
      development, deserves further attention.

PMID- 24436207
TI  - Improving stability and biocompatibility of alginate/chitosan microcapsule by
      fabricating bi-functional membrane.
AB  - Cell encapsulation technology holds promise for the cell-based therapy. But poor
      mechanical strength and biocompatibility of microcapsule membrane are still
      obstacles for the clinical applications. A novel strategy is presented to prepare
      AC1 C2 A microcapsules with bi-functional membrane (that is, both desirable
      biocompatibility and membrane stability) by sequentially complexing chitosans
      with higher deacetylation degree (C1) and lower deacetylation degree (C2) on
      alginate (A) gel beads. Both in vitro and in vivo evaluation of AC1C2 A
      microcapsules demonstrate higher membrane stability and less cell adhesion,
      because the introduction of C2 increases membrane strength and decreases surface
      roughness. Moreover, diffusion test of AC1C2 A microcapsules displays no inward
      permeation of IgG protein suggesting good immunoisolation function. The results
      demonstrate that AC1C2 A microcapsules with bi-functional membrane could be a
      promising candidate for microencapsulated cell implantation with cost effective
      usage of naturally biocompatible polysaccharides.

PMID- 24436208
TI  - HPLC-PDA-ORD bioassay of S-(+) and R-(-) clopidogrel on rat dried blood spots.
AB  - A simple and rapid chiral high-performance liquid chromatography (HPLC) method
      was developed and validated for bioanalysis of clopidogrel enantiomers on rat
      dried blood spots (DBS). Clopidogrel enantiomers were extracted from DBS using
      ethanol: methanol (80:20, v/v) and separated on a Chiralcel OJ-H column
      containing cellulose tris (4-methly benzoate) as a polysaccharide stationary
      phase using n-hexane-ethanol-diethylamine (70:30, 0.1 v/v) as a mobile phase at a
      flow rate of 1.0 mL/min. The detection was carried out at 220 nm using a
      photodiode array (PDA) detector while the elution order of the enantiomers was
      determined by a polarimeter connected to PDA in series. The effect of hematocrit
      on extraction of clopidogrel enantiomers from DBS was evaluated and no
      interference from endogenous substances was noticed. The overall accuracy of (R)
      and (S) enantiomers of clopidogrel from DBS were 91.6 and 89.2%, respectively.
      The calibration curves were linear over the concentration range of 1-500 ug/mL
      for both enantiomers. The results show that the method is specific, precise, and
      reproducible (intra- and interday precision relative standard deviations (RSDs)
      <10.0%). The stability of racemic clopidogrel was performed under all storage
      conditions and the results were found to be well within the acceptance limits.

PMID- 24436209
TI  - Evaluation of hypopharyngeal carcinoma using high-resolution ultrasound:
      comparison with CT.
AB  - BACKGROUND: To evaluate the role of sonography (US) in assessing hypopharyngeal
      carcinoma when compared with CT. METHODS: A randomized prospective study was
      performed on 40 biopsy-proven cases of hypopharyngeal carcinoma.Contrast-enhanced
      CT of the neck was performed in all patients, followed by US. Sonographic
      identification of any tumor extension into the extralaryngeal soft tissues,
      postcricoid space, subglottis, thyroid gland, esophagus, and across the midline
      was recorded. US observations and CT findings were compared and then correlated
      with the histopathologic findings in 14 operative cases. In the remaining 26
      inoperable cases, US was compared only with CT. RESULTS: Our cohort was composed
      of 38 men and 2 women ranging in age from 36 to 59 years. In a subset of 14
      operative patients, US had a sensitivity of 71.4% (10/14), while CT achieved a
      sensitivity of 92.8% (13/14), and the difference was not statistically
      significant (p > 0.05). US and CT findings concurred in 67.5% (27/40) of cases.
      CONCLUSIONS: Even though small tumors are difficult to visualize, US can play a
      significant role in the assessment of tumor extension within and beyond the
      larynx, especially when cross-sectional imaging is either unavailable or
      unaffordable.

PMID- 24436210
TI  - Biosynthetic origin of the antibiotic cyclocarbamate brabantamide A (SB-253514)
      in plant-associated Pseudomonas.
AB  - Within the framework of our genome-based program to discover new antibiotic
      lipopeptides from Pseudomonads, brabantamides A-C were isolated from plant
      associated Pseudomonas sp. SH-C52. Brabantamides A-C displayed moderate to high
      in vitro activities against Gram-positive bacterial pathogens. Their shared
      structure is unique in that they contain a 5,5-bicyclic carbamate scaffold. Here,
      the biosynthesis of brabantamide A (SB-253514) was studied by a combination of
      bioinformatics, feeding experiments with isotopically labelled precursors and in
      vivo and in vitro functional analysis of enzymes encoded in the biosynthetic
      pathway. The studies resulted in the deduction of all biosynthetic building
      blocks of brabantamide A and revealed an unusual feature of this metabolite: its
      biosynthesis occurs via an initially formed linear di-lipopeptide that is
      subsequently rearranged by a novel FAD-dependent Baeyer-Villiger monooxygenase.

PMID- 24436211
TI  - Acute exposure to a 2 mT static magnetic field affects ionic homeostasis of in
      vitro grown porcine granulosa cells.
AB  - In this work, we provided direct evidence for the first time that exposure to a
      static magnetic field (SMF) of low intensity (2 mT) is immediately followed by a
      reversible cell membrane depolarization wave (of about 1 min) that causes the
      rise of intracellular calcium and the decrease of mitochondrial activity of vital
      granulosa cells. These effects are likely due to the increase in Na(+) and Ca(2+)
      cell membrane permeability.

PMID- 24436212
TI  - Biofilm models for the food industry: hot spots for plasmid transfer?
AB  - Biofilms represent a substantial problem in the food industry, with food
      spoilage, equipment failure, and public health aspects to consider. Besides,
      biofilms may be a hot spot for plasmid transfer, by which antibiotic resistance
      can be disseminated to potential foodborne pathogens. This study investigated
      biomass and plasmid transfer in dual-species (Pseudomonas putida and Escherichia
      coli) biofilm models relevant to the food industry. Two different configurations
      (flow-through and drip-flow) and two different inoculation procedures (donor
      recipient and recipient-donor) were tested. The drip-flow configuration
      integrated stainless steel coupons in the setup while the flow-through
      configuration included a glass flow cell and silicone tubing. The highest biomass
      density [10 log (cells cm-2)] was obtained in the silicone tubing when first the
      recipient strain was inoculated. High plasmid transfer ratios, up to 1/10
      (transconjugants/total bacteria), were found. Depending on the order of
      inoculation, a difference in transfer efficiency between the biofilm models could
      be found. The ease by which the multiresistance plasmid was transferred
      highlights the importance of biofilms in the food industry as hot spots for the
      acquisition of multiresistance plasmids. This can impede the treatment of
      foodborne illnesses if pathogens acquire this multiresistance in or from the
      biofilm. 

PMID- 24436213
TI  - Assessing eating disorder symptoms in adolescence: is there a role for multiple
      informants?
AB  - OBJECTIVES: Studies of adolescent psychiatric disorders often collect information
      from adolescents and parents, yet most eating disorder epidemiologic studies only
      rely on adolescent report. METHOD: We studied the eating disorder symptom
      reports, from questionnaires sent at participants' ages 14 and 16 years, provided
      by 7,968 adolescents from the Avon Longitudinal Study of Parents and Children
      (ALSPAC), and their parents. Adolescents and parents were asked questions about
      the adolescent's eating disorder symptoms (binge eating, vomiting, laxative use,
      fasting, and thinness). We assessed cross-sectional concordance and prevalence
      using kappa coefficients and generalized estimating equations. Generalized
      estimating equations were used to assess prospective associations between symptom
      reports and adolescent weight outcomes measured at a face-to-face assessment at
      17.5 years. RESULTS: Parents and adolescents were largely discordant on symptom
      reports cross-sectionally (kappas < 0.3), with the parent generally less likely
      to report bulimic symptoms than the adolescent but more likely to report
      thinness. Female adolescents were more likely to report bulimic symptoms than
      males (e.g., two to four times more likely to report binge eating), while
      prevalence estimates according to parent reports of female vs. male adolescents
      were similar. Both informants' symptom reports were predictive of body mass and
      composition measures at 17.5 years; compared to adolescent report, parentally
      reported binge eating was more strongly predictive of body mass index.
      DISCUSSION: Parent report of eating disorder symptoms seemed to measure
      different, but potentially important, aspects of these symptoms during
      adolescence. Epidemiologic eating disorder studies should consider the potential
      value added from incorporating parental reports, particularly in studies of
      males.

PMID- 24436214
TI  - Expression of SNMP1 and SNMP2 genes in antennal sensilla of Spodoptera exigua
      (Hubner).
AB  - Sensory neuron membrane proteins (SNMPs) are olfactory-specific, two
      transmembrane proteins. Previous publications reported that SNMP1 is expressed on
      the dendrite membrane of pheromone-sensitive neurons in Heliothis virescens and
      is an essential cofactor for pheromone detection in Drosophila. In this study, we
      cloned two SNMP genes (GenBank accession nos. JX469106 and JX469107) from the
      antenna of the beet armyworm moth Spodoptera exigua (Lepidoptera: Hubner). These
      SNMP genes are classified into two highly conserved subclades, indicating their
      importance in physiological activity of lepidopteran insects. SexiSNMP1 is
      antenna-specific in male and female adults, while SexiSNMP2 is antenna-abundant
      but also expressed in other chemosensory tissues, particularly proboscises and
      maxillary palps of adults both sexes. In situ hybridization revealed that both
      SNMPs are broadly expressed in long and short trichoid and basiconic sensilla. We
      infer that SNMP1 and SNMP2 act in the detection of the sex pheromone and general
      odorants. 

PMID- 24436215
TI  - In vitro assessment of the Lenz effect on heart valve prostheses at 1.5 T.
AB  - PURPOSE: Increasing numbers of patients with cardiac valve prostheses are being
      referred for magnetic resonance imaging (MRI) despite concerns about the
      potential for functional valve impedance due to Lenz forces. This study aims to
      determine, in vitro, the occurrence of Lenz forces on 9 heart valve prostheses at
      1.5 T and assess the risk of impedance of valve function. MATERIALS AND METHODS:
      A specially designed hydro-pneumatic system was used to record pressure changes
      across the valve indicative of any MR induced alteration in leaflet performance.
      Nine cardiac valve prostheses were exposed to the B0 field at 1.5 T. Each valve
      was advanced through the B0 field and continuous signals from high frequency
      pressure transducers were recorded and pressure drops across the valve were
      assessed using time correction superimposition. The delta p across the valve was
      assessed as a marker of any MRI induced alteration in leaflet performance.
      RESULTS: All prostheses produced sinusoidal waveforms. Profiles were asymmetrical
      and there was no consistency in complex shape and valve type/sub-group.
      Irregularities in pressure profiles of 4 prostheses were detected indicating
      resistance of the occluder to the B0 field. CONCLUSION: This study provides
      empirical evidence of the Lenz Effect on cardiac valve prostheses exposed to the
      MR B0 field causing functional valve impedance and increasing the risk of
      valvular regurgitation and reduced cardiac output. Thus, it is essential to
      consider the potential for the Lenz Effect when scanning cardiac valve implant
      patients in order to safeguard their wellbeing.

PMID- 24436216
TI  - Performance on the Wisconsin card-sorting test and serum levels of glial cell
      line-derived neurotrophic factor in patients with major depressive disorder.
AB  - INTRODUCTION: Some evidence suggests that neurotrophic growth factor systems
      might be involved in the etiology of major depressive disorder (MDD). Glial cell
      line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the
      transforming growth factor-beta family that plays a role in the development and
      function of the brain. This study aimed to test whether GDNF in serum was
      abnormal in MDD, and whether it was related to the cognitive impairment of MDD.
      METHODS: Serum GDNF levels in MDD patients (n = 32) and normal controls (n = 32)
      were measured with the enzyme-linked immunosorbent assay method. All subjects
      were assessed for performance on the Wisconsin card-sorting test (WCST). RESULTS:
      Performance on the WCST in MDD patients was significantly poorer than that in
      controls. Serum GDNF levels in MDD patients were significantly decreased compared
      to that of the control subjects (P < 0.001). Furthermore, the decrease in the
      serum GDNF levels positively correlated with performance in the WCST-% CONC and
      negatively with performance in the WCST-P in MDD patients. DISCUSSION: The
      findings suggest that MDD patients have extensive impairments of executive
      functioning, and lower serum GDNF might be involved in the pathogenesis of MDD,
      which may be associated with the cognitive dysfunction in MDD patients.

PMID- 24436217
TI  - Splenic sarcoidosis remains a diagnostic challenge.

PMID- 24436218
TI  - The chiral separation and enantioselective degradation of the chiral herbicide
      napropamide.
AB  - The chiral pesticide enantiomers often have different toxic effects and
      environmental behaviors, which suggests that the risk assessments should be on an
      enantiomeric level. In this work, the chiral separation of the napropamide
      enantiomers and the stereoselective degradation in tomato, cucumber, rape,
      cabbage, and soil were investigated. Napropamide enantiomers could be separated
      absolutely by high-performance liquid chromatography (HPLC) using a Chiralpak IC
      column with a resolution factor of 11.75 under the optimized condition. Solid
      phase extraction (SPE) was used for cleanup of the enantiomers in the vegetable
      samples. The residue analysis method was validated. Good linearities (R(2)  =
      0.9997) and recoveries (71.43% -97.64%) were obtained. The limits of detection
      (LOD) were 0.05 mg/kg in soil and 0.20 mg/kg in vegetables. The results of
      degradation showed that napropamide dissipated rapidly in vegetables with half
      lives of only 1.13-2.21 days, but much more slowly in soil, with a half-life of
      11.95 d. Slight stereoselective degradation of the two enantiomers was only
      observed in cabbage, with enantiomeric fraction (EF) = 0.46, and there was no
      enantioselectivity in the other vegetables. The degradation of napropamide in the
      five matrixes was fast, and there was no enantioselectivity.

PMID- 24436219
TI  - Maintenance of statin use over 3 years following acute coronary syndromes: a
      national data linkage study (ANZACS-QI-2).
AB  - OBJECTIVE: To describe patterns of statin use and predictors of poor maintenance
      over a 3-year period following an acute coronary syndrome (ACS). METHODS:
      National hospitalisation, mortality and pharmaceutical dispensing data were
      linked for all subjects aged 35-84 years discharged from a public hospital with
      an ACS in New Zealand in 2007. A Medication Possession Ratio (MPR; percentage of
      follow-up days patients were dispensed statins) was calculated for each patient.
      Adequate maintenance was defined by a MPR >=80%. RESULTS: In 2007, 11 348
      patients aged 35-84 years were discharged from hospital with ACS. Within 90 days
      of discharge, 83% had received a statin. Over the follow-up period, 66% were
      adequately maintained on a statin (MPR >=80%): 69% in the first year, 67% in the
      second year and 66% in the third year. Patients taking statins prior to admission
      and those who underwent a coronary procedure were 20-50% more likely to have a
      MPR >=80% over 3 years than others. In contrast, people aged 35-45 years and
      those of Maori or Pacific ethnicity were 13-25% less likely to have a MPR >=80%
      than those aged 55-64 years and Europeans. CONCLUSIONS: One-third of patients
      were not adequately maintained on statins over the 3-year period following ACS,
      but 82% of those on a statin prior to admission had an MPR >=80% over 3 years of
      follow-up. These findings define achievable treatment levels and identify groups
      who may benefit from efforts to improve statin use.

PMID- 24436220
TI  - Trends in hospital treatments, including revascularisation, following acute
      myocardial infarction, 2003-2010: a multilevel and relative survival analysis for
      the National Institute for Cardiovascular Outcomes Research (NICOR).
AB  - OBJECTIVE: To investigate temporal changes in survival after acute myocardial
      infarction (AMI) by early invasive strategy. METHODS: Accelerated failure time
      and 6-month relative survival analyses stratified by thrombolysis or primary
      percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction
      (STEMI) and coronary angiography for non-STEMI (NSTEMI) encompassing 583 466
      patients across 247 hospitals in England and Wales over hospital admission
      periods 2003-2004, 2005-2006, 2007-2008 and 2009-2010. RESULTS: Survival improved
      significantly for STEMI patients who received reperfusion therapy (time ratio
      (TR) 1.47, 95% CI 1.22 to 2.78) and was stable for those who did not (TR 1.02,
      95% CI 0.85 to 1.22). While there were significant improvements in survival for
      NSTEMI patients who underwent coronary angiography (TR 1.39, 95% CI 1.18 to
      1.62), there was a significant decline for those who did not (TR 0.70, 95% CI
      0.65 to 0.75). Patients without reperfusion therapy or coronary angiography had a
      greater number of comorbidities, but the use of secondary prevention medications
      was comparable with patients who received reperfusion therapy or coronary
      angiography. There was a significant hospital-level survival effect, with higher
      crude 6-month mortality in hospitals in the lowest coronary angiography and PPCI
      quartiles (angiography Q1: 16.4% vs Q4: 12.8%; PPCI Q1: 15.8% vs Q4: 12.4%).
      CONCLUSIONS: Survival rates after AMI have improved. Whereas survival estimates
      for STEMI patients who did not receive reperfusion therapy were stable, they
      worsened for NSTEMI patients not receiving coronary angiography.

PMID- 24436221
TI  - Ischaemic heart disease, influenza and influenza vaccination: a prospective case
      control study.

PMID- 24436222
TI  - Methods for comparing center-specific survival outcomes using direct
      standardization.
AB  - The evaluation of center-specific outcomes is often through survival analysis
      methods. Such evaluations must account for differences in the distribution of
      patient characteristics across centers. In the context of censored event times,
      it is also important that the measure chosen to evaluate centers not be
      influenced by imbalances in the center-specific censoring distributions. The
      practice of using center indicators in a hazard regression model is often
      invalid, inconvenient, or undesirable to carry out. We propose a semiparametric
      version of the standardized rate ratio (SRR) useful for the evaluation of centers
      with respect to a right-censored event time. The SRR for center j can be
      interpreted as the ratio of the expected number of deaths in the total population
      (if the total population were in fact subject to the center j mortality hazard)
      to the observed number of events. The proposed measure is not affected by
      differences in center-specific covariate or censoring distributions. Asymptotic
      properties of the proposed estimators are derived, with finite-sample properties
      examined through simulation studies. The proposed methods are applied to national
      kidney transplant data.

PMID- 24436223
TI  - Solid-phase synthesis and biological evaluation of N-dipeptido L-homoserine
      lactones as quorum sensing activators.
AB  - Bacteria use small signaling molecules to communicate in a process termed "quorum
      sensing" (QS), which enables the coordination of survival strategies, such as
      production of virulence factors and biofilm formation. In Gram-negative bacteria,
      these signaling molecules are a series of N-acylated L-homoserine lactones. With
      the goal of identifying non-native compounds capable of modulating bacterial QS,
      a virtual library of N-dipeptido L-homoserine lactones was screened in silico
      with two different crystal structures of LasR. The 30 most promising hits were
      synthesized on HMBA-functionalized PEGA resin and released through an efficient
      acid-mediated cyclative release mechanism. Subsequent screening for modulation of
      QS in Pseudomonas aeruginosa and E. coli identified six moderately strong
      activators. A follow-up library designed from the preliminary derived structure
      activity relationships was synthesized and evaluated for their ability to
      activate the QS system in this bacterium. This resulted in the identification of
      another six QS activators (two with low micromolar activity) thus illuminating
      structural features required for QS modulation.

PMID- 24436224
TI  - Possible risks due to exposure of workers and patients with implants by TETRA
      transmitters.
AB  - Several studies have demonstrated that mobile telephones that use different
      technologies, such as Global System for Mobile Communication (GSM) or Universal
      Mobile Telecommunication System (UMTS), have the potential to influence the
      functionality of active electronic implants, including cardiac pacemakers.
      According to these studies, a few safety measures, such as maintaining minimum
      distances of 25 cm between implants and transmitters, are sufficient to avoid
      such effects. Terrestrial Trunked Radio (TETRA) has become a well-established
      communication standard in many countries, including Germany and Austria. TETRA
      transmitters are typically used by police forces and emergency services.
      Employees and volunteers working for such institutions are often in close contact
      with patients, causing TETRA transmitters to potentially have an impact on the
      functionality of the implants of patients. Therefore, the main focus of our study
      was to investigate the functionality of several types of implants when exposed to
      TETRA transmitters. Moreover, we investigated the difference in the degree of
      exposure of users of TETRA transmitters when they carry the devices in different
      locations near the body, and when they use them in different positions near the
      head. Our results show that a compliance distance of 30 cm between implant and
      transmitter is sufficient to exclude any influence on the examined implants. All
      examined exposure conditions demonstrated that the levels were well below
      recommended limits. If a user wants to minimize their exposure, use of
      transmitters in front of the mouth leads to somewhat lower exposure when compared
      to typical mobile phone like use.

PMID- 24436225
TI  - Accelerating phase-encoded proton MR spectroscopic imaging by compressed sensing.
AB  - PURPOSE: To develop a phase encoding reduction scheme based on compressed sensing
      (CS) for phase-encoded (1) H MR spectroscopic imaging (MRSI). MATERIALS AND
      METHODS: Phantom and in vivo rat brain MRSI experiments were performed at 7 Tesla
      to examine the performance of CS approach and compare it with the full k-space
      acquisition. The CS undersampling was performed by acquiring a pseudorandom and
      density-varying subset of phase encodings. Residual water resonance was first
      removed from the undersampled k-space dataset before CS reconstruction. The CS
      reconstruction was performed by a linearized Bregman iteration procedure for
      efficiency in computing large scale L1 minimization. The spectral and spatial
      fidelity was evaluated by comparing spectral linewidths and metabolite maps and
      voxel-wise Bland-Altman analysis. RESULTS: CS preserved the spectral resolution
      and metabolite content levels. No spectral broadening was observed, and the
      estimation biases of the metabolite content levels were no more than 4%. CS
      clearly preserved the boundaries of metabolite maps but led to slight loss of
      details in metabolite maps. CONCLUSION: This study demonstrated the feasibility
      of the proposed CS approach to accelerate phase-encoded (1) H MRSI.

PMID- 24436226
TI  - Hyperthermia-induced drug delivery from thermosensitive liposomes encapsulated in
      an injectable hydrogel for local chemotherapy.
AB  - A novel drug delivery system, enabling an in situ, thermally triggered drug
      release is described, consisting of an injectable thermoresponsive chitosan
      hydrogel containing doxorubicin-loaded thermosensitive liposomes. The design,
      fabrication, characterization, and an assessment of in vitro bioactivity of this
      formulation is detailed. Combining on-demand drug delivery with in situ gelation
      results in a promising candidate for local chemotherapy. 

PMID- 24436227
TI  - Reducing contrast contamination in radial turbo-spin-echo acquisitions by
      combining a narrow-band KWIC filter with parallel imaging.
AB  - PURPOSE: Cartesian turbo spin-echo (TSE) and radial TSE images are usually
      reconstructed by assembling data containing different contrast information into a
      single k-space. This approach results in mixed contrast contributions in the
      images, which may reduce their diagnostic value. The goal of this work is to
      improve the image contrast from radial TSE acquisitions by reducing the
      contribution of signals with undesired contrast information. METHODS: Radial TSE
      acquisitions allow the reconstruction of multiple images with different T2
      contrasts using the k-space weighted image contrast (KWIC) filter. In this work,
      the image contrast is improved by reducing the band-width of the KWIC filter.
      Data for the reconstruction of a single image are selected from within a small
      temporal range around the desired echo time. The resulting dataset is
      undersampled and, therefore, an iterative parallel imaging algorithm is applied
      to remove aliasing artifacts. RESULTS: Radial TSE images of the human brain
      reconstructed with the proposed method show an improved contrast when compared
      with Cartesian TSE images or radial TSE images with conventional KWIC
      reconstructions. CONCLUSION: The proposed method provides multi-contrast images
      from radial TSE data with contrasts similar to multi spin-echo images.
      Contaminations from unwanted contrast weightings are strongly reduced.

PMID- 24436228
TI  - Synthesis, antitubulin, and antiproliferative SAR of C3/C1-substituted
      tetrahydroisoquinolines.
AB  - The syntheses and antiproliferative activities of novel substituted
      tetrahydroisoquinoline derivatives and their sulfamates are discussed. Biasing of
      conformational populations through substitution on the tetrahydroisoquinoline
      core at C1 and C3 has a profound effect on the antiproliferative activity against
      various cancer cell lines. The C3 methyl-substituted sulfamate (+/-)-7-methoxy-2
      (3-methoxybenzyl)-3-methyl-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (6 b),
      for example, was found to be ~10-fold more potent than the corresponding non
      methylated compound 7-methoxy-2-(3-methoxybenzyl)-6-sulfamoyloxy-1,2,3,4
      tetrahydroisoquinoline (4 b) against DU-145 prostate cancer cells (GI50 values:
      220 nM and 2.1 MUM, respectively). Such compounds were also found to be active
      against a drug-resistant MCF breast cancer cell line. The position and nature of
      substitution of the N-benzyl group in the C3-substituted series was found to have
      a significant effect on activity. Whereas C1 methylation has little effect on
      activity, introduction of C1 phenyl and C3-gem-dimethyl substituents greatly
      decreases antiproliferative activity. The ability of these compounds to inhibit
      microtubule polymerisation and to bind tubulin in a competitive manner versus
      colchicine confirms the mechanism of action. The therapeutic potential of a
      representative compound was confirmed in an in vivo multiple myeloma xenograft
      study.

PMID- 24436229
TI  - Mechanism of an unusual, but clinically significant, digoxin-bupropion drug
      interaction.
AB  - An unusual, but clinically significant, digoxin (DIG)-bupropion (BUP) drug
      interaction (DDI), in which BUP increased DIG renal clearance by 80% is reported.
      To investigate the mechanism(s) of this unusual DDI, first the effect of BUP, its
      circulating metabolites or their combination on [(3) H]-DIG transport by cells
      expressing human P-gp or human OATP4C1 was determined. Second, the study asked
      whether this DDI could be replicated in the rat so that it could be used to
      conduct mechanistic studies. Then, the effect of BUP and its rat metabolites on
      [(3) H]-DIG transport were tested by cells expressing rat Oatp4c1. Bupropion and
      its metabolites had no effect on human P-gp mediated transepithelial transport of
      [(3) H]-DIG. Bupropion and hydroxybupropion (HBUP) significantly stimulated H
      OATP4C1 mediated transport of [(3) H]-DIG. In addition, BUP cocktail (BUP plus
      its metabolites) significantly increased the H-OATP4C1 mediated transport of [(3)
      H]-DIG, and partially reversed the inhibition by 100 um DIG. However, erythro
      hydrobupropion (EBUP) and threo-hydrobupropion (TBUP) did not affect the [(3) H]
      DIG uptake by H-OATP4C1 cells. Bupropion administration significantly increased
      digoxin renal clearance in rats. Surprisingly, bupropion significantly inhibited
      r-Oatp4c1 mediated transport of [(3) H]-DIG at clinically relevant unbound plasma
      concentrations of BUP or those observed in the rat study, while HBUP or TBUP did
      not. These data support our hypothesis that at clinically relevant plasma
      concentrations, bupropion and its metabolites activate H-OATP4C1 mediated DIG
      tubular secretion, and could possibly explain the increase in digoxin renal
      clearance produced by bupropion. While bupropion increased digoxin renal
      clearance in the rat, it appeared to do so by inhibiting r-Oatp4c1-mediated
      digoxin renal reabsorption.

PMID- 24436230
TI  - Advances in stroke: Advances in interventional radiology 2013.

PMID- 24436231
TI  - Letter by Price et al regarding article, "Does use of the recognition of stroke
      in the emergency room stroke assessment tool enhance stroke recognition by
      ambulance clinicians?".

PMID- 24436232
TI  - Advances in stroke: Health policy/outcomes research 2013.

PMID- 24436233
TI  - Advances in stroke: Population studies 2013.

PMID- 24436235
TI  - Response to letter regarding article, "Does use of the recognition of stroke in
      the emergency room stroke assessment tool enhance stroke recognition by ambulance
      clinicians?".

PMID- 24436236
TI  - Advances in stroke: Prevention and health services delivery 2012-2013.

PMID- 24436237
TI  - Advances in stroke: Imaging 2013.

PMID- 24436239
TI  - Letter by Brandler and Sharma regarding article, "Does use of the recognition of
      stroke in the emergency room stroke assessment tool enhance stroke recognition by
      ambulance clinicians?".

PMID- 24436234
TI  - Multilocus genetic risk score associates with ischemic stroke in case-control and
      prospective cohort studies.
AB  - BACKGROUND AND PURPOSE: Genome-wide association studies have revealed multiple
      common variants associated with known risk factors for ischemic stroke (IS).
      However, their aggregate effect on risk is uncertain. We aimed to generate a
      multilocus genetic risk score (GRS) for IS based on genome-wide association
      studies data from clinical-based samples and to establish its external validity
      in prospective population-based cohorts. METHODS: Three thousand five hundred
      forty-eight clinic-based IS cases and 6399 controls from the Wellcome Trust Case
      Control Consortium 2 were used for derivation of the GRS. Subjects from the
      METASTROKE consortium served as a replication sample. The validation sample
      consisted of 22 751 participants from the Cohorts for Heart and Aging Research in
      Genomic Epidemiology consortium. We selected variants that had reached genome
      wide significance in previous association studies on established risk factors for
      IS. RESULTS: A combined GRS for atrial fibrillation, coronary artery disease,
      hypertension, and systolic blood pressure significantly associated with IS both
      in the case-control samples and in the prospective population-based studies.
      Subjects in the top quintile of the combined GRS had >2-fold increased risk of IS
      compared with subjects in the lowest quintile. Addition of the combined GRS to a
      simple model based on sex significantly improved the prediction of IS in the
      combined clinic-based samples but not in the population-based studies, and there
      was no significant improvement in net reclassification. CONCLUSIONS: A multilocus
      GRS based on common variants for established cardiovascular risk factors was
      significantly associated with IS both in clinic-based samples and in the general
      population. However, the improvement in clinical risk prediction was found to be
      small.

PMID- 24436240
TI  - Mild hypothermia after intravenous thrombolysis in patients with acute stroke: a
      randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Hypothermia improves outcome in resuscitated patients and
      newborns with hypoxic brain injury. We studied the safety and feasibility of mild
      hypothermia in awake patients with stroke after intravenous thrombolysis.
      METHODS: Patients were randomized 1:1 to mild hypothermia (35 degrees C) or to
      standard stroke unit care within 6 hours of symptom onset. Hypothermia was
      induced with a surface-cooling device and cold saline infusions. Active cooling
      was restrained gradually after 12 hours at <35.5 degrees C. The primary outcome
      measure was the number of patients with <36 degrees C body temperature for >80%
      of the 12-hour cooling period. RESULTS: We included 36 patients with a median of
      National Institutes of Health Stroke Scale score of 9 one hour after
      thrombolysis. Fifteen of 18 (83%) patients achieved the primary end point.
      Sixteen (89%) patients reached <35.5 degrees C in a median time of 10 hours
      (range, 7-16 hours) from symptom onset, spent 10.5 hours (1-17 hours) in
      hypothermia, and were back to normothermia in 23 hours (15-29 hours). Few serious
      adverse events were more common in the hypothermia group. At 3 months, 7 patients
      (39%) in both groups had good outcome (modified Ranking Scale, 0-2), whereas poor
      outcome (modified Ranking Scale, 4-6) was twice as common in the normothermia
      group (44% versus 22%). CONCLUSIONS: Mild hypothermia with a surface-cooling
      device in an acute stroke unit is safe and feasible in thrombolyzed,
      spontaneously breathing patients with stroke, despite the adverse events.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00987922.

PMID- 24436241
TI  - Advances in critical care/emergency medicine 2013.

PMID- 24436242
TI  - Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human
      squamous carcinoma cells.
AB  - Proprotein convertases (PC), a family of serine proteases, process cancer-related
      substrates such as growth factors, growth factor receptors, cell adhesion
      molecules, metalloproteinases, etc. HIF-1alpha is a major transcription factor
      involved in tumorigenesis by sensing intratumoral hypoxia. Furin (PCSK3) is one
      of the numerous target genes regulated by HIF-1alpha transactivation and its
      distribution into endosomal compartments and onto the cell surface can be
      triggered by hypoxia via HIF-1alpha. siRNAs to knockdown PCs were transfected
      into cells alone or in combination with different drug treatments. Protein and
      RNA expression levels were analyzed by Western blotting or RT-PCR, respectively.
      PC7 (PCSK7) and furin siRNAs upregulated HIF-1alpha protein under normoxic
      condition to a level similar to that obtained by cobalt chloride treatment,
      eventually leading to activation of VEGF-A synthesis in two human head and neck
      squamous cell carcinoma cell lines. The unchanged levels of HIF-1alpha mRNA
      expression under siRNA treatment and the additive HIF-1alpha induction of PC
      siRNAs and either cobalt chloride or the 26S ribosome inhibitor, MG-132,
      suggested a post-transcriptional PC-mediated regulation. Furthermore,
      cycloheximide chase showed that PC7/furin siRNA regulation occurred at the level
      of HIF-1alpha translation. A specific IGF-1R signaling inhibitor was able to
      attenuate the PC siRNA induction of HIF-1alpha, suggesting the involvement of the
      IGF-1R pathway. Thus, the data show that PCs regulate HIF-1alpha. Furin and PC7
      siRNAs induced HIF-1alpha protein by increasing its translation, resulting in
      upregulation of VEGF-A. This finding may provide insight into intricate PC
      functions that seem to be independent from their substrate-processing activity.

PMID- 24436244
TI  - Fine needle aspiration of primary mediastinal synovial sarcoma: cytomorphologic,
      immunohistochemical, and molecular study.
AB  - The cytologic diagnosis of synovial sarcoma (SS) can be difficult when it occurs
      in unusual locations, atypical age groups, and/or have unusual morphology. We
      report a case of primary mediastinal SS in a 65-year-old male with a long smoking
      history who presented with increasing shortness of breath and was found to have a
      14.2 cm mediastinal mass. Smears from the endobronchial ultrasound guided fine
      needle aspiration of the mass were moderately cellular consisting of loosely
      cohesive clusters, some of which demonstrated nuclear molding, and dispersed
      single cells. The relatively uniform tumor cells had a high nuclear-to
      cytoplasmic ratio, finely granular chromatin, and inconspicuous nucleoli. Some of
      the single cells had spindled morphology with unipolar wispy tails and naked
      nuclei. Based on the clinical presentation and the cytomorphologic features, our
      initial differential diagnoses included atypical carcinoid, small cell carcinoma,
      basaloid squamous cell carcinoma, sarcoma, and lymphoma. Immunohistochemical
      studies on the cell block sections revealed that the tumor cells were focally
      positive for cytokeratin and diffusely positive for CD56, while negative for
      CD45, synaptophysin and chromogranin. Ultimately, an immunohistochemical stain
      for TLE-1 demonstrated diffusely strong nuclear positivity and molecular studies
      showed the presence of the t(X; 18) SYT/SSX1 translocation confirming the
      diagnosis of SS. In this report, we describe the cytomorphologic features of SS,
      its diagnostic pitfalls, and potential mimics in the mediastinum.

PMID- 24436243
TI  - Catalytic scope of the thiamine-dependent multifunctional enzyme cyclohexane-1,2
      dione hydrolase.
AB  - The thiamine diphosphate (ThDP)-dependent enzyme cyclohexane-1,2-dione hydrolase
      (CDH) was expressed in Escherichia coli and purified by affinity chromatography
      (Ni-NTA). Recombinant CDH showed the same C-C bond-cleavage and C-C bond
      formation activities as the native enzyme. Furthermore, we have shown that CDH
      catalyzes the asymmetric cross-benzoin reaction of aromatic aldehydes and
      (decarboxylated) pyruvate (up to quantitative conversion, 92-99 % ee). CDH
      accepts also hydroxybenzaldehydes and nitrobenzaldehydes; these previously have
      not (or only in rare cases) been known as substrates of other ThDP-dependent
      enzymes. On a semipreparative scale, sterically demanding 4-(tert
      butyl)benzaldehyde and 2-naphthaldehyde were transformed into the corresponding 2
      hydroxy ketone products in high yields. Additionally, certain benzaldehydes with
      electron withdrawing substituents were identified as potential inhibitors of the
      ligase activity of CDH.

PMID- 24436238
TI  - Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.
AB  - BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of
      future stroke may improve with a genetic risk score (GRS) based on single
      nucleotide polymorphisms associated with stroke and its risk factors. METHODS:
      The study includes 4 population-based cohorts with 2047 first incident strokes
      from 22,720 initially stroke-free European origin participants aged >=55 years,
      who were followed for up to 20 years. GRSs were constructed with 324 single
      nucleotide polymorphisms implicated in stroke and 9 risk factors. The association
      of the GRS to first incident stroke was tested using Cox regression; the GRS
      predictive properties were assessed with area under the curve statistics
      comparing the GRS with age and sex, Framingham Stroke Risk Score models, and
      reclassification statistics. These analyses were performed per cohort and in a
      meta-analysis of pooled data. Replication was sought in a case-control study of
      ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham
      Stroke Risk Score, age and sex model resulted in a significant improvement in
      discrimination (all stroke: Deltajoint area under the curve=0.016, P=2.3*10(-6);
      ischemic stroke: Deltajoint area under the curve=0.021, P=3.7*10(-7)), although
      the overall area under the curve remained low. In all the studies, there was a
      highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS:
      The single-nucleotide polymorphisms associated with stroke and its risk factors
      result only in a small improvement in prediction of future stroke compared with
      the classical epidemiological risk factors for stroke.

PMID- 24436246
TI  - Volumetric arterial wall shear stress calculation based on cine phase contrast
      MRI.
AB  - PURPOSE: To assess the accuracy and precision of a volumetric wall shear stress
      (WSS) calculation method applied to cine phase contrast magnetic resonance
      imaging (PC-MRI) data. MATERIALS AND METHODS: Volumetric WSS vectors were
      calculated in software phantoms. WSS algorithm parameters were optimized and the
      influence of spatial resolution and segmentation was evaluated. Subsequently, 2D
      cine PC-MRI data in the carotid and the aorta at varying spatial resolutions were
      obtained (n = 2) and compared with the simulations. Finally, volumetric WSS was
      calculated in 3D cine PC-MRI data of the carotid bifurcation and the aorta (n =
      6). RESULTS: We found that at least 8 voxels across the diameter are required to
      obtain a WSS accuracy of 5% and a precision of 20% in software phantoms.
      Systematic WSS quantification errors up to 40% were found in the case of
      segmentation errors. The in vivo measurements using 2D cine PC-MRI exhibited WSS
      increase at increasing spatial resolutions, similar to the results in software
      phantoms. Volumetric WSS vectors were successfully calculated in three healthy
      carotid bifurcations and aortas. CONCLUSION: The effects of resolution and
      segmentation on the accuracy and precision of the WSS algorithm were quantified.
      We were able to calculate volumetric WSS in the carotid bifurcation and the
      aorta.

PMID- 24436245
TI  - Cytologic findings of gastric schwannoma: a case report.
AB  - Spindle cell lesions of the stomach are rare. They usually affect the submucosa
      or muscularis propria and therefore can be sampled by endoscopic fine needle
      aspiration. The most common tumor in this category is gastrointestinal stromal
      tumor (GIST), followed by leiomyoma and gastric schwannoma. Gastric schwannoma is
      a benign tumor of neuroectodermal origin that has overlapping
      morphologic/cytologic features with GIST and leiomyoma. Gastric schwannomas
      differ from peripheral schwannomas by lacking a capsule, Verocay bodies, Antoni B
      areas, and thick-walled vessels. They are characterized morphologically by poorly
      defined borders, cuffs of lymphoid tissue and a haphazard spindle cell
      proliferation. We present here the cytologic and histopathologic features of a
      gastric schwannoma. The tumor was composed of spindle cells with delicate
      eosinophilic cytoplasm and wavy nuclei, with an associated conspicuous lymphoid
      backdrop. The latter feature raised the possibility of a lymphoid lesion, a
      problem cytopathologists should be aware of.

PMID- 24436247
TI  - A longitudinal study assessing lens thickness changes in the eye of the growing
      beagle using ultrasound scanning: relevance to age of dogs in regulatory
      toxicology studies.
AB  - The lens is formed in utero with new secondary lens fibres added as outer layers
      throughout life in a growth pattern characteristic of the species. This study
      examined the time course of beagle lens growth to better understand the optimal
      starting age of dogs for safety studies to support adult versus paediatric
      indications, and to assess the feasibility of non-invasively monitoring lens
      growth with high frequency ultrasound. Ultrasound scanning was performed in six
      female beagle dogs using the Vevo770. All dogs were imaged in B-mode using local
      anaesthetic but without sedation. Imaging was carried out every 2 weeks from 8 to
      22 weeks of age and then monthly until 62 weeks of age. The dogs tolerated the
      procedure well. The lens was visible in all dogs and measuring the lens thickness
      with high frequency ultrasound demonstrated good analytical reproducibility [Root
      Mean Square (RMS) = 3.13%]. No differences between the left and right eye existed
      and lens thickness correlated with body weight. The highest weekly growth rate
      was before 12 weeks of age. A statistically significant difference between
      monthly thickness was detected until 42 weeks of age at which point growth
      reached a plateau. During the experiment, lenses grew by 29.7% reaching an
      average thickness of 6.4 mm +/- 0.03. By 10 months of age (the typical age used
      for routine toxicological evaluation), beagles have reached a plateau in lens
      growth that is analogous to human adults. Where lens is a target organ of concern
      it is suggested that beagles under 6 months old may be a better model for
      determining paediatric safety.

PMID- 24436248
TI  - Analysis of proton-density bias corrections based on T1 measurement for robust
      quantification of water content in the brain at 3 Tesla.
AB  - PURPOSE: Estimating tissue water content using high field MRI, such as 3 Tesla
      (T), is challenging due to the difficulty in dissociating the radio frequency
      inhomogeneity pattern from the signal arising from tissue intrinsic proton
      density (PD) variations. To overcome this problem the longitudinal relaxation
      time T1 can be combined with an initial guess of the PD to yield the desired PD
      bias correction. However, it is necessary to know whether T1 effects, i.e., any
      effect contributing to T1 while being independent of tissue hydration, influence
      the estimated correction. METHODS: Twenty-five healthy subjects underwent a
      quantitative 3T MRI protocol enabling acquisition of 64 slices with 1 mm in-plane
      resolution and 2 mm slice thickness in 14 min. Influence of T1 effects on the
      estimated water content map is evaluated using a dedicated method including T1
      and T2 * information and region of interest-based water content values are
      compared with the literature. RESULTS: Our analysis indicates that the PD bias
      correction based on T1 is largely insensitive to T1 effects. Besides, water
      content results are in good agreement with literature values obtained at 1.5T.
      CONCLUSION: This study demonstrates the applicability of a PD bias correction
      based on T1 to yield tissue water content at 3T.

PMID- 24436249
TI  - Structural basis for the inhibition of AKR1B10 by caffeic acid phenethyl ester
      (CAPE).
AB  - Caffeic acid phenethyl ester (CAPE), the major bioactive component of honeybee
      propolis, is a potent selective inhibitor of aldo-keto reductase family member
      1B10 (AKR1B10), and a number of derivatives hold promise as potential anticancer
      agents. However, sequence homology between AKR1B10 and other members of the
      superfamily, including critical phase I metabolizing enzymes, has resulted in a
      concern over the selectivity of any potential therapeutic agent. To elucidate the
      binding mode of CAPE with AKR1B10 and to provide a tool for future in silico
      efforts towards identifying selective inhibitors, the crystal structure of
      AKR1B10 in complex with CAPE was determined. The observed interactions provide an
      explanation for the selectivity exhibited by CAPE for AKR1B10, and could be used
      to guide further derivative design.

PMID- 24436250
TI  - On one leg: trehalose monoesters activate macrophages in a Mincle-dependant
      manner.
AB  - The C22 and C26 trehalose monoesters, each containing a single acyl chain, were
      synthesised in good overall yields and found to activate macrophages in a Mincle
      dependent manner. The activities of the monoesters paralleled those of their
      diester counterparts, and both mono- and diesters could activate the immune
      response in the absence of priming. This is the first time that trehalose
      monoesters have been found to activate macrophages, and these studies thus
      provide an important framework for the rational design of other Mincle agonists.

PMID- 24436251
TI  - Standardized predictive values.

PMID- 24436252
TI  - Improved screening for cystic fibrosis-related diabetes by an integrated care
      team using an algorithm.
AB  - OBJECTIVE: To determine whether implementation of a standardized, clinic-based
      algorithm improves compliance with cystic fibrosis-related diabetes (CFRD)
      screening guidelines. STUDY DESIGN: A CFRD screening algorithm was developed as
      part of a quality improvement initiative through collaboration between the
      pediatric pulmonary and endocrine divisions and implemented prospectively to
      children aged 8-17 years in our CF center for a 6-month period. The primary
      outcome measure was the percentage rate of CF patients who were appropriately
      screened with an oral glucose tolerance test (OGTT) during the quality
      improvement period as compared to the year prior. RESULTS: Ninety-seven percent
      (37/38) of OGTTs were appropriately ordered by providers, and 89% (34/38) of
      patients obtained the OGTT at the completion of the quality improvement period.
      Compared with the percentage of eligible patients completing the OGTT the year
      prior, the use of the algorithm significantly improved screening (P = 0.03). Data
      collected 1-year post-algorithm implementation revealed 97% (33/34) of OGTTs were
      ordered and 79% (27/34) of OGTTs were completed. The use of the algorithm 1-year
      post-implementation did not reveal a significant improvement in screening when
      compared to the reference year and implementation period (P = 0.08). CONCLUSIONS:
      Implementation of a clinical algorithm resulted in a statistically significant
      improvement in screening during the quality improvement period, but this
      improvement was not sustained the following year despite continued physician
      compliance with ordering the OGTT. Barriers to patient compliance need to be
      explored.

PMID- 24436254
TI  - FlatNJ: a novel network-based approach to visualize evolutionary and
      biogeographical relationships.
AB  - Split networks are a type of phylogenetic network that allow visualization of
      conflict in evolutionary data. We present a new method for constructing such
      networks called FlatNetJoining (FlatNJ). A key feature of FlatNJ is that it
      produces networks that can be drawn in the plane in which labels may appear
      inside of the network. For complex data sets that involve, for example, non
      neutral molecular markers, this can allow additional detail to be visualized as
      compared to previous methods such as split decomposition and NeighborNet. We
      illustrate the application of FlatNJ by applying it to whole HIV genome
      sequences, where recombination has taken place, fluorescent proteins in corals,
      where ancestral sequences are present, and mitochondrial DNA sequences from gall
      wasps, where biogeographical relationships are of interest. We find that the
      networks generated by FlatNJ can facilitate the study of genetic variation in the
      underlying molecular sequence data and, in particular, may help to investigate
      processes such as intra-locus recombination. FlatNJ has been implemented in Java
      and is freely available at www.uea.ac.uk/computing/software/flatnj.

PMID- 24436253
TI  - The effects of a MAP2K5 microRNA target site SNP on risk for anxiety and
      depressive disorders.
AB  - Functional variants that contribute to genomewide association study (GWAS)
      signals are difficult to identify. MicroRNAs could contribute to some of these
      gene-trait relationships. We compiled a set of GWAS trait gene SNPs that were
      predicted to affect microRNA regulation of mRNA. Trait associations were tested
      in a sample of 6725 European-American (EA) and African-American (AA) subjects
      that were interviewed using the polydiagnostic SSADDA to diagnose major
      psychiatric disorders. A predicted miR-330-3p target site SNP (rs41305272) in
      mitogen-activated protein kinase kinase 5 (MAP2K5) mRNA was in LD (d' = 1.0, r(2)
      = 0.02) with a reported GWAS-identified variant for restless legs syndrome (RLS),
      a disorder frequently comorbid with anxiety and depression, possibly because of a
      shared pathophysiology. We examined the SNP's association with mood and anxiety
      related disorders. Rs41305272 was associated with agoraphobia (Ag) in EAs (odds
      ratio [OR] = 1.95, P = 0.007; 195 cases) and AAs (OR = 3.2, P = 0.03; 148 cases)
      and major depressive disorder (MDD) in AAs (OR = 2.64, P = 0.01; 427 cases), but
      not EAs (465 cases). Rs41305272*T carrier frequency was correlated with the
      number of anxiety and depressive disorders diagnosed per subject. RLS was not
      evaluated in our subjects. Predicted miR-330-3p target genes were enriched in
      pathways relevant to psychiatric disorders. These findings suggest that microRNA
      target site information may be useful in the analysis of GWAS signals for complex
      traits. MiR-330-3p and MAP2K5 are potentially important contributors to mood and
      anxiety-related traits. With support from additional studies, these findings
      could add to the large number of risk genes identified through association to
      medical disorders that have primary psychiatric effects.

PMID- 24436256
TI  - Effect of Carr-Purcell refocusing pulse trains on transverse relaxation times of
      metabolites in rat brain at 9.4 Tesla.
AB  - PURPOSE: To investigate the effect of Carr-Purcell (CP) pulse trains on
      transverse relaxation times, T2, of tissue water and metabolites (both noncoupled
      and J-coupled spins) in the rat brain at 9.4 Tesla (T) using LASER, CP-LASER, and
      T2rho-LASER sequences. METHODS: Proton NMR spectra were measured in rat brain in
      vivo at 9.4T. Spectra were acquired at multiple echo times ranging from 18 to 402
      ms. All spectra were analyzed using LCModel with simulated basis sets. Signals of
      metabolites as a function of echo time were fitted using a mono-exponential
      function to determine their T2 relaxation times. RESULTS: Measured T2 s for
      tissue water and all metabolites were significantly longer with CP-LASER and
      T2rho-LASER compared with LASER. The T2 increased by a factor of ~ 1.3 for
      noncoupled and weakly coupled spins (e.g., N-acetylaspartate and total creatine)
      and by a factor of ~ 2 (e.g., glutamine and taurine) to ~ 4 (e.g., glutamate and
      myo-inositol) for strongly coupled spins. CONCLUSION: Application of a CP pulse
      train results in a larger increase in T2 relaxation times for strongly coupled
      spins than for noncoupled (singlet) and weakly coupled spins. This needs to be
      taken into account when correcting for T2 relaxation in CP-like sequences such as
      LASER.

PMID- 24436257
TI  - Arecoline stimulated early growth response-1 production in human buccal
      fibroblasts: suppression by epigallocatechin-3-gallate.
AB  - BACKGROUND: Early growth response-1 (Egr-1) protein plays an important role in
      many human fibrotic diseases. Areca nut chewing is the most important risk factor
      of oral submucous fibrosis (OSF). METHODS: Egr-1 protein expression in OSF was
      examined using antibody to Egr-1. Arecoline-induced Egr-1 expression and its
      signaling pathways were assessed by Western blot analyses in human buccal mucosal
      fibroblasts (BMFs). RESULTS: Elevated Egr-1 staining was observed in epithelial
      cells, fibroblast, and inflammatory cells in 7 of 10 OSF cases. Arecoline, a main
      alkaloid found in the areca nut, stimulated Egr-1 synthesis in BMFs. Pretreatment
      with antioxidant N-acetyl-L-cysteine, c-Jun NH2-terminal kinase inhibitor
      SP600125, and extracellular signal-regulated kinase inhibitor PD98059
      significantly reduced arecoline-induced Egr-1 synthesis. Epigallocatechin-3
      gallate (EGCG) inhibited arecoline-induced Egr-1 synthesis and collagen gel
      contraction in a dose-responsive manner. CONCLUSION: Constitutive Egr-1
      expression during areca nut chewing may play a role in the pathogenesis of OSF.
      EGCG could be a good candidate for prevention or treatment of OSF.

PMID- 24436255
TI  - Transfer and functional consequences of dietary microRNAs in vertebrates:
      concepts in search of corroboration: negative results challenge the hypothesis
      that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates,
      but important questions persist.
AB  - If validated, diet-derived foreign microRNA absorption and function in consuming
      vertebrates would drastically alter our understanding of nutrition and ecology.
      RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by
      uptake of environmental RNA and amplification and systemic distribution of RNAi
      effectors. Therapeutic exploitation of RNAi in treating human disease is
      difficult because these accessory processes are absent or diminished in most
      animals. A recent report challenged multiple paradigms, suggesting that ingested
      microRNAs (miRNAs) are transferred to blood, accumulate in tissues, and exert
      canonical regulation of endogenous transcripts. Independent replication of these
      findings has been elusive, and multiple disconfirmatory findings have been
      published. In the face of mounting negative results, any additional positive
      reports must provide the proverbial "extraordinary proof" to support such claims.
      In this article, we review the evidence for and against a significant role for
      dietary miRNAs in influencing gene expression, and make recommendations for
      future studies. Also watch the Video Abstract. 

PMID- 24436258
TI  - A synthetic approach for constructing the 3/6/6/5-fused tetracyclic skeleton of
      tenuipesine A.
AB  - An efficient approach toward the 3/6/6/5-fused tetracyclic skeleton of
      tenuipesine A has been accomplished. The strategy featured 1) a tandem Mitsunobu
      and 3,3-rearrangement reaction yielding the key intermediate 7 with two adjacent
      all-carbon quaternary centers with high d.r.; and 2) a tandem DBDMH-mediated
      semipinacol rearrangement via a 1,2-oxygen migration of an allylic hemiketal to
      construct the highly substituted tetrahydropyran ring. 

PMID- 24436259
TI  - Education and training in pathology and laboratory medicine.

PMID- 24436260
TI  - Improving diagnostic pathology capacity for global cancer care: where to start.

PMID- 24436261
TI  - Mesothelial proliferations: useful marker is not the same as a diagnostic one.

PMID- 24436262
TI  - Building a laboratory workforce to meet the future: ASCP Task Force on the
      Laboratory Professionals Workforce.
AB  - OBJECTIVES: To analyze the demand for services from the nation's medical
      laboratories, which is predicted to dramatically increase as our citizens age and
      millions receive insurance coverage through the Affordable Care Act. METHODS: A
      systematic review of relevant publications and databases was conducted to assess
      the current state of the nation's medical laboratory workforce and to examine the
      impact of population demographics and health reform on workforce development to
      address the future demand for laboratory services. RESULTS: Building a Laboratory
      Workforce to Meet the Future, a new report from the American Society for Clinical
      Pathology (ASCP), provides a comprehensive strategy to address the future
      workforce needs of the nation's medical laboratories to meet this demand to
      provide timely, accurate, and safe patient care and to fully realize the benefits
      of personalized medicine. CONCLUSIONS: The report, from the ASCP Task Force on
      the Laboratory Professionals Workforce, is a comprehensive review of the myriad
      of factors affecting recruitment and retention of qualified laboratory
      professionals and provides a set of thoughtful recommendations outlining a
      multifaceted approach to bolster the pipeline of potential candidates for the
      profession as well as leadership in health care.

PMID- 24436263
TI  - Molecular genetics of pancreatic neoplasms and their morphologic correlates: an
      update on recent advances and potential diagnostic applications.
AB  - OBJECTIVES: To summarize the most clinically and biologically relevant advances
      in molecular/genetic characteristics of various pancreatic neoplasms, with
      morphologic correlation. METHODS: Whole-exome sequencing of numerous benign and
      malignant pancreatic tumors, along with the plethora of highly sensitive
      molecular studies now available for analyzing these tumors, provide mounting
      evidence to support the long-held belief that cancer is essentially a genetic
      disease. These genetic discoveries have not only helped to confirm the age-old,
      morphology-based classifications of pancreatic neoplasia but have shed new light
      on their mechanisms. Many of these molecular discoveries are currently being used
      in preoperative diagnosis. RESULTS: Mutations in KRAS, P16/CDKN2A, TP53, and
      SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors;
      ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread
      metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in
      most intraductal pancreatic mucinous neoplasms, providing critical molecular
      fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in
      pancreatic neuroendocrine tumors, making it a useful potential marker in
      distinguishing these tumors from mimics. CONCLUSIONS: When combined with
      morphologic observations, molecular studies will increase our understanding of
      the pathogenesis and morphomolecular signatures associated with specific
      neoplasms and provide new horizons for precision medicine and targeted therapies.

PMID- 24436264
TI  - Implementation of a national external quality assessment program for medical
      laboratories in Burkina Faso: challenges, lessons learned, and perspectives.
AB  - OBJECTIVES: The National External Quality Assessment (NEQA) program of Burkina
      Faso is a proficiency testing program mandatory for all laboratories in the
      country since 2006. The program runs two cycles per year and covers all areas of
      laboratories. METHODS: All panels were validated by the expert committee before
      dispatch under optimal storage and transport conditions to participating
      laboratories along with report forms. RESULTS: Performance in the last 5 years
      varied by panel, with average annual performance of bacteriology panels for all
      laboratories rising from 75% in 2006 to 81% in 2010 and with a best average
      performance of 87% in 2007 and 2008. During the same period, malaria microscopy
      performance varied from 85% to 94%, with a best average performance of 94% in
      2010; chemistry performance increased from 87% to 94%, with a best average annual
      performance of 97% in 2009. Hematology showed more variation in performance,
      ranging from 61% to 86%, with a best annual average performance of 90% in 2008.
      Average annual performance for immunology varied less between 2006 and 2010,
      recording 97%, 90%, and 95%. Except for malaria microscopy, annual performances
      for enrolled panels varied substantially from year to year, indicating some
      difficulty in maintaining consistency in quality. CONCLUSIONS: The main
      challenges of the NEQA program observed between 2006 to 2010 were funding,
      sourcing, and safe transportation of quality panels to all laboratories
      countrywide.

PMID- 24436265
TI  - Measurement of improvement achieved by participation in international laboratory
      accreditation in sub-Saharan Africa: the Aga Khan University Hospital Nairobi
      experience.
AB  - OBJECTIVES: As part of the ISO 15189:2007 accreditation process, the Aga Khan
      University Hospital Nairobi laboratory became the first internationally
      accredited hospital laboratory in sub-Saharan Africa outside South Africa in 2011
      through the South Africa National Accreditation System. METHODS: Seven
      preanalytic, 10 analytic, eight postanalytic, and five administrative performance
      parameters were monitored from 2009 to 2012 to measure the impact of the
      accreditation process. RESULTS: Most measures in all four categories showed
      substantial improvement. The seven preanalytic measures all showed major
      improvement-between a quarter and a half sigma. Real but less dramatic
      improvement appeared in analytic and postanalytic measures, but greater than one
      sigma decrease in analytic "procedure violations" and a three-quarter sigma
      decrease in excessive turnaround time were noted in these categories.
      Administrative improvements included dramatic decreases in misdirected and
      missing reports and complaints. CONCLUSIONS: This study demonstrates the
      correlation of the accreditation process with improvement in quality measures in
      a low-resource region.

PMID- 24436266
TI  - NF-kappaB and COX-2 expression in nonmalignant endometrial lesions and cancer.
AB  - OBJECTIVES: To examine the immunohistochemical expression of cyclooxygenase-2
      (COX-2) and nuclear factor-kappaB (NF-kappaB) in benign endometrial polyps (EPs),
      endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and
      endometrioid endometrial cancer (EC). METHODS: The immunohistochemical expression
      of COX-2 and NF-kappaB was performed using an Aperio Scanscope XT automated
      system in 218 patients with endometrioid EC and 107 patients with nonmalignant
      endometrial lesions: 53 with benign EPs, 37 with EH, and 17 with EIN. RESULTS:
      COX-2 and NF-kappaB p50 expression were significantly lower in EC compared with
      nonmalignant lesions. We observed significant decreased NF-kappaB p65 expression
      in EC vs EPs (P < .001) and EH (P = .014) as well as in EIN vs. EPs (P = .01).
      For patients with EC, COX-2 correlated positively with NF-kappaB p65 and NF
      kappaB p50 (P < .001). Grade 3 tumors had a higher mean expression of NF-kappaB
      p65 (P = .03). NF-kappaB p50, NF-kappaB p65, and COX-2 expression had no impact
      on survival. CONCLUSIONS: We conclude that COX-2 and NF-kappaB expression are
      lower in EC compared with nonmalignant endometrial lesions. COX-2 and NF-kappaB
      expression have no prognostic value in EC.

PMID- 24436267
TI  - Diafiltration MALDI-TOF mass spectrometry method for culture-independent
      detection and identification of pathogens directly from urine specimens.
AB  - OBJECTIVES: With the aim of rapid, culture-independent identification of
      microorganisms directly from urine specimens, we developed a diafiltration matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) method. METHODS: In this procedure, urine specimens are desalted,
      fractionated, and concentrated prior to MS analysis. The analytic performance
      characteristics of the diafiltration method were assessed in a prospective trial
      whereby 100 fresh urine specimens were processed using diafiltration MALDI-TOF
      MS. Concomitant with this, conventional culture was performed with results
      blinded to the MS operator. RESULTS: The diafiltration method correctly
      identified urine specimens positive for uropathogens (Escherichia coli,
      Klebsiella pneumoniae, and Proteus mirabilis) and correctly classified all
      specimens negative for clinically relevant bacteriuria, including a subset of
      contaminated urine specimens and a subset with growth of clinically insignificant
      flora. The sensitivity and specificity of the assay were 67% and 100%,
      respectively. The detection limit of this method was 10(5) to 10(6) colony
      forming units/mL. CONCLUSIONS: Using the diafiltration method, we were able to
      improve the turnaround time for microorganism identification from 24 to 48 hours
      (for conventional culture) to 2 to 3 hours. Although methodological refinements
      are under way to further improve the clinical sensitivity and turnaround time,
      the 100% positive predictive value of this method suggests that it could be used
      to guide the selection of antimicrobial agents.

PMID- 24436268
TI  - A probabilistic analysis of mitotic counts in melanoma.
AB  - OBJECTIVES: Mitotic counts in melanoma are important and have now become part of
      the staging of this tumor. Yet, this change was largely based on studies that
      evaluated the mitotic counts in a limited fashion. Because counts of things with
      a microscope are often distributed as a Poisson random variable, the major goal
      of this study was to uncover the probabilistic nature of mitotic counts in
      melanoma. METHODS: Specifically, a general double Poisson model was applied to
      mitotic counts in 53 cutaneous melanomas representing both thin and thick tumors.
      RESULTS: The general double Poisson probability model fit the data well. A single
      Poisson function was sufficient for 46 of the 53 study cases, and two Poisson
      functions were required for seven cases because of tissue heterogeneity.
      Furthermore, the success of the model implied that there is a high probability
      for false-negative mitotic counts, especially in thin melanomas, and that the
      "hot" spot methodology introduces bias. CONCLUSIONS: Mitotic counts in melanomas
      are a probabilistic phenomenon closely related to the Poisson probability
      distribution, and this factor needs to be considered when using mitotic counts
      for staging and prognosis in melanoma.

PMID- 24436269
TI  - Immunohistochemical reevaluation of carbonic anhydrase IX (CA IX) expression in
      tumors and normal tissues.
AB  - OBJECTIVES: To immunohistochemically evaluate the carbonic anhydrase IX (CA IX)
      expression on 1,551 cases of tumors and normal tissues from various organs.
      METHODS: Immunohistochemical evaluation of the expression of CA IX was performed
      on 1,125 malignant tumors, 69 benign neoplasms, and 322 normal tissues on tissue
      microarray sections and 18 intrahepatic cholangiocarcinomas (ICCs) and 17
      hepatocellular carcinomas (HCCs) on routine sections. RESULTS: There was
      overexpression of CA IX in clear cell renal cell carcinoma (CRCC) (88%, 68/77).
      Twenty-six (90%) of 29 ICCs were positive. In contrast, only 5 (15%) of 34 HCCs
      were focally positive. No staining was seen in chromophobe renal cell carcinoma
      (ChRCC), oncocytoma, seminoma, or carcinomas of the breast, thyroid, or prostate.
      All normal renal tubules except one case showed no staining. CONCLUSIONS: These
      data demonstrate the diagnostic utility of CA IX in (1) differentiating CRCC from
      ChRCC and oncocytomas, (2) distinguishing low-grade CRCC from normal renal
      tubules in small samples, (3) separating ICC from HCC, and (4) identifying
      metastatic CRCC from other metastases with clear cell features.

PMID- 24436270
TI  - High expression of TNFSF13 in tumor cells and fibroblasts is associated with poor
      prognosis in non-small cell lung cancer.
AB  - OBJECTIVES: To examine high expression of tumor necrosis factor ligand
      superfamily member 13 (TNFSF13), which is correlated with several malignancies.
      METHODS: TNFSF13 messenger RNA expression in tumor cells and fibroblasts in a
      cohort of patients with non-small cell lung cancer (NSCLC) was analyzed by
      quantitative real-time polymerase chain reaction and immunohistochemistry using a
      tissue microarray. RESULTS: TNFSF13 expression was significantly higher in lung
      adenocarcinomas compared with squamous cell carcinomas (P = .022). High TNFSF13
      expression in NSCLC stroma was related with low differentiation (P = .045) and
      sex (male > female, P = .005). Cox proportional hazards regression univariate and
      multivariable analysis revealed TNFSF13 expression in NSCLC tumor cells (P =
      .007) or fibroblasts (P = .027) as an independent prognostic factor in the 5-year
      overall survival rate. CONCLUSIONS: Our findings indicate TNFSF13 is a prognostic
      factor in NSCLC and suggest TNFSF13 may be a novel therapeutic target for NSCLC.

PMID- 24436271
TI  - Increased immunoglobulin (Ig) G4-positive plasma cell density and IgG4/IgG ratio
      are not specific for IgG4-related disease in the skin.
AB  - OBJECTIVES: Immunoglobulin (Ig) G4-related disease (IgG4-RD), a fibroinflammatory
      condition that can affect multiple organs, is suggested by lymphoplasmacytic
      inflammation, fibrosis, phlebitis, and increased IgG4+ plasma cell (PC) tissue
      density. In patients with suspected IgG4-RD and skin changes, skin biopsy may
      serve as a diagnostic screen or to supplement nondiagnostic visceral biopsy
      specimens. We aimed to determine whether increased cutaneous IgG4+ PCs or
      IgG4/IgG ratio is specific for IgG4-RD. METHODS: We examined 50 mucocutaneous
      specimens representing seven PC-rich dermatoses and reactive PC-rich infiltrates
      with IgG and IgG4 immunohistochemical stains. RESULTS: IgG4+ density exceeded 10
      cells per high-power field in 22 (44%) of 50 specimens, representing six of seven
      diagnoses and reactive infiltrates. In five specimens (10%), the IgG4/IgG ratio
      exceeded 0.40. CONCLUSIONS: Moderately elevated IgG4+ PC density or IgG4/IgG
      ratio is a nonspecific finding in the skin. In cutaneous biopsy specimens showing
      increased IgG4+ PCs, careful consideration should be given to clinical,
      serologic, and other histopathologic features before attributing clinical changes
      to IgG4-RD.

PMID- 24436272
TI  - Low-grade squamous intraepithelial lesion/cannot exclude high-grade squamous
      intraepithelial lesion (LSIL-H) is a unique category of cytologic abnormality
      associated with distinctive HPV and histopathologic CIN 2+ detection rates.
AB  - OBJECTIVES: To examine data correlating high-risk human papillomavirus (hrHPV)
      results in patients with both low-grade squamous intraepithelial lesion (LSIL)
      and atypical squamous cells cannot exclude high-grade squamous intraepithelial
      lesion (ASC-H) cytology findings (LSIL-H) with follow-up histopathology. METHODS:
      A total of 494 LSIL-H ThinPrep (Hologic, Marlborough, MA) cases with hrHPV
      testing were identified. Histopathologic follow-up was available in 347 patients.
      RESULTS: Among 347 patients with follow-up histopathology after LSIL-H cytology
      and hrHPV testing, 90.5% tested hrHPV positive. Cervical intraepithelial
      neoplasia (CIN) 2/3 was diagnosed in 29.4% and CIN 1 in 53.6%. CIN 2/3 was
      diagnosed in significantly more patients with hrHPV-positive LSIL-H than
      following hrHPV-negative LSIL-H results. Compared with published institutional
      data, LSIL-H had significantly lower hrHPV and histopathologic CIN 2/3+ rates
      (90.5% and 29.4%, with no cervical cancers) than high-grade squamous
      intraepithelial lesion (HSIL) (95.7% and 70.5%, with 2.4% cervical cancers) but
      higher rates than LSIL (80.2% and 12.9%) or atypical squamous cells/cannot
      exclude HSIL (ASC-H) (54.3% and 17.2%). Whereas CIN 2/3 detection rates were
      similar in HPV-positive LSIL-H and HPV-positive ASC-H, CIN 2/3 findings were more
      likely with HPV-negative LSIL-H than with HPV-negative ASC-H. CONCLUSIONS: LSIL-H
      is a unique category of cytologic abnormality associated with distinctive hrHPV
      and CIN 2/3+ diagnostic rates.

PMID- 24436273
TI  - Whole-genome single nucleotide polymorphism array analysis is complementary to
      classical cytogenetic analysis in the evaluation of lymphoid proliferations.
AB  - OBJECTIVES: To explore how much additional information single nucleotide
      polymorphism (SNP) arrays provide and whether they could partially replace
      classical cytogenetics. METHODS: Twenty-six lymphoid proliferations with
      available cytogenetic studies were analyzed with the Affymetrix Genome-Wide Human
      SNP Array 6.0 (Affymetrix, Santa Clara, CA). RESULTS: Eleven of 26 cases
      demonstrated complete concordance between cytogenetics and SNP analysis, and 10
      of 26 cases demonstrated partial concordance. Five discordant cases had copy
      number abnormalities (CNAs) with cytogenetics not identified with SNP arrays.
      While SNP analysis showed CNAs not apparent by cytogenetics in eight cases and
      helped clarify the karyotype in six cases, cytogenetics demonstrated CNAs not
      seen by SNP analysis in 15 cases as well as balanced translocations in 12 cases.
      CONCLUSIONS: The combination of cytogenetics and SNP analysis results in a higher
      overall yield in identifying numerical chromosomal abnormalities than either
      technique alone.

PMID- 24436274
TI  - A centralized recipient database enhances the serologic safety of RBC
      transfusions for patients with sickle cell disease.
AB  - OBJECTIVES: To evaluate the utility of a centralized transfusion service model in
      preventing the transfusion of incompatible units in patients with sickle cell
      disease (SCD). METHODS: The serologic records of transfused patients with SCD
      were reviewed. The index hospital was where an alloantibody was initially
      detected. RESULTS: In total, 150 patients with SCD were evaluated; 66 (44.0%) of
      150 were alloimmunized. In 42 (63.6%) of these patients, 1 or more antibodies
      evanesced. The median number of hospitals visited by patients with SCD for RBC
      transfusion with 1 or more evanesced antibodies was three (range, one to eight);
      the median number of nonindex hospitals was two (range, one to seven). Of the
      patients with evanesced antibodies, 28.6% received transfusions at various
      nonindex hospitals 20 or more times after the antibody evanesced. CONCLUSIONS: A
      centralized database can help identify patients with SCD who have evanesced
      alloantibodies and prevent issuing incompatible RBC units.

PMID- 24436275
TI  - Performance of various laboratory assays in the measurement of dabigatran in
      patients receiving therapeutic doses: a prospective study based on peak and
      trough plasma levels.
AB  - OBJECTIVES: To study dabigatran etexilate, a new oral anticoagulant that
      functions as a direct thrombin inhibitor. METHODS: This study evaluates four
      methods, one of which is performed in three different laboratories, and compares
      results against dabigatran levels measured by Boehringer-Ingelheim (Ingelheim,
      Germany) using mass spectrometry. RESULTS: Although routine monitoring is not
      required, measurement of plasma concentrations may be necessary in certain
      clinical situations. Routine coagulation assays such as the prothrombin time,
      activated partial thromboplastin time, and thrombin time do not reliably
      determine levels of dabigatran anticoagulation. Alternative assays, when
      calibrated with a dabigatran standard, such as the modified dilute thrombin time,
      ecarin clotting time, and ecarin chromogenic assay, may be appropriate, although
      a comparison of these methods using samples from patients taking dabigatran has
      not been performed. CONCLUSIONS: Although results using all methods in this study
      demonstrate adequate correlation, measured dabigatran levels varied in a
      statistically significant manner, even when the same method was used by different
      laboratories. The clinical significance of this variation in dabigatran
      concentrations is uncertain.

PMID- 24436276
TI  - Pattern analysis of Epstein-Barr virus viremia and its significance in the
      evaluation of organ transplant patients suspected of having posttransplant
      lymphoproliferative disorders.
AB  - OBJECTIVES: To explore posttransplant lymphoproliferative disorder (PTLD) cases
      associated with Epstein-Barr virus (EBV). METHODS: We retrospectively reviewed
      the EBV DNA quantitation data of 9,779 blood samples from 740 transplant patients
      and their associations with PTLD. RESULTS: EBV viremia occurred more frequently
      in patients with PTLD (85.4%) in comparison with patients without PTLD (38.3%; P
      < .0001). Patients with PTLD demonstrated significantly higher first positive
      results, higher peak levels, and a higher rate of increase in EBV viral load
      compared with patients without PTLD (P = .002, P < .0001, and P < .0001,
      respectively). However, in the multivariate analysis, only the peak level was
      associated with the development of PTLD. In particular, within hematopoietic stem
      cell recipients, the peak level able to diagnose PTLD was an area under the
      receiver operating characteristic curve of 0.806. CONCLUSIONS: We believe that
      pattern analysis of EBV DNA quantitation results could lead to the early
      diagnosis and timely treatment of PTLD.

PMID- 24436277
TI  - Clinicopathologic correlation of leiomyoma with clinical findings and secondary
      changes in a rural population of north India.
AB  - OBJECTIVES: To examine the clinicopathologic profile of leiomyoma in surgically
      removed uteri in a rural tertiary care hospital of north India between January
      2008 and August 2012. METHODS: Fibroids are the most common benign tumors of
      reproductive-age women, with the genital tract being the most common site for
      tumors. The type of fibroids and secondary changes were confirmed by
      histopathologic examination of excised uteri. RESULTS: Of the 200 patients with
      clinically suspected uterine fibroids, diagnosis was confirmed in 180. An
      intramural variant was most common (66.7%), followed by the subserosal (22.2%),
      submucosal (8.9%), and cervical (2.2%) varieties. Menorrhagia, abdominal mass,
      and abdominal pain were the most common clinical symptoms associated with
      intramural leiomyoma. Metrorrhagia was observed with submucosal leiomyoma.
      Secondary changes such as hyaline, mucoid, cystic, and fatty degeneration were
      also seen, most commonly in intramural leiomyoma. CONCLUSIONS: This study
      examined the clinicopathologic profile of leiomyoma and is being presented on
      account of its rarity. To the best of the authors' knowledge, such a study on a
      rural population of North India has not been done previously. It revealed that
      intramural leiomyoma was the most common variant and menorrhagia was the prime
      clinical symptom. Secondary changes such as hyaline, mucoid, cystic, and fatty
      degeneration were also seen, most commonly in intramural leiomyoma.

PMID- 24436278
TI  - Double minutes and MYC amplification: a combined May-Grunwald Giemsa and
      fluorescence in situ hybridization study.
AB  - OBJECTIVES: To report the demonstration of double minutes with MYC amplification
      in a case of myeloproliferative neoplasm with monocytosis in transformation by a
      combination of standard karyotyping and interphase and metaphase fluorescence in
      situ hybridization (FISH). METHODS: To determine the lineage involvement, we
      applied combined morphology and an interphase FISH study using dual-color break
      apart probes for MYC on peripheral blood film. RESULTS: MYC amplification was
      demonstrated in both myeloid and monocytic cells but not lymphocytes. The MYC
      amplification was not associated with loss of MYC signals at the homologous 8q24
      regions where the genes were located. Furthermore, the extent of MYC
      amplification has been shown to diminish as the granulocytes mature. CONCLUSIONS:
      Combined morphology and FISH study has shown a pluripotent myeloid disorder and
      also an inverse relationship between cell maturity and MYC amplification.

PMID- 24436279
TI  - Washed RBCs prevent recurrent acute hypotensive transfusion reactions.
AB  - OBJECTIVES: To examine whether a liver transplant patient, who was not taking an
      angiotensin-converting enzyme inhibitor and developed two episodes of hypotension
      with systolic pressure in the 50s within minutes of starting an RBC transfusion,
      may have had a disturbance in the production and metabolism of bradykinin and des
      Arg(9)-BK. METHODS: All patient information was obtained by reviewing the
      electronic medical record, the transfusion service database, and transfusion
      reaction investigation records. RESULTS: The blood pressure returned to normal
      once the transfusions were discontinued. In an effort to mitigate the acute
      hypotension, the blood products were washed. Subsequently, the patient received
      three additional packed RBC transfusions without further incidents of
      hypotension. CONCLUSIONS: Our experience suggests that washing the products was
      an acceptable and effective preventative measure to avoid further acute
      hypotensive transfusion reactions in patients unable to metabolize these
      vasodilators present in the donor units.

PMID- 24436280
TI  - Hepatic ALECT-2 amyloidosis causing portal hypertension and recurrent variceal
      bleeding: a case report and review of the literature.
AB  - OBJECTIVES: To examine laser microdissection and mass spectrometry (LMD-MS),
      which has emerged as a new tool to aid in typing amyloid proteins. RESULTS: ALECT
      2 is a potential cause of hepatic amyloidosis best detected by LMD-MS. METHODS:
      One of the more recently reported proteins is ALECT-2 (leukocyte cell-derived
      chemotaxin 2) amyloid, found in renal specimens of Hispanic patients. Here we
      report the first case of hepatic ALECT-2 amyloidosis diagnosed by LMD-MS from a
      liver biopsy specimen of a 52-year-old Hispanic man and causing portal
      hypertension with recurrent esophageal variceal bleeding. CONCLUSIONS: ALECT-2
      can cause amyloidosis in organs other than the kidneys. It should be strongly
      considered in Hispanic patients and in those with a globular pattern of amyloid
      deposition. The incidence of ALECT-2 amyloidosis is likely underreported.

PMID- 24436282
TI  - Light-controlled formation of vesicles and supramolecular organogels by a
      cholesterol-bearing amphiphilic molecular switch.
AB  - A new responsive material composed of an amphiphilic light-switchable
      dithienylethene unit functionalized with a hydrophobic cholesterol unit and a
      hydrophilic poly(ethylene glycol)-modified pyridinium group has been designed.
      This unique single-molecule system shows responsive light-switchable self
      assembly in both water and organic solvents. Light-triggered reversible vesicle
      formation in aqueous solutions is reported. The molecule shows a different
      behavior in apolar aromatic solvents, in which light-controlled formation of
      organogel fibers is observed. The light-triggered aggregation behavior of this
      molecule demonstrates that control of a supramolecular structure with light can
      be achieved in both aqueous and organic media and that this ability can be
      present in a single molecule. This opens the way toward the effective development
      of new strategies in soft nanotechnology for applications in controlled chemical
      release systems. 

PMID- 24436283
TI  - Successful management of Panton-Valentine leukocidine-positive necrotising
      pneumonia and A/H1N12009 influenzavirus coinfection in adult.
AB  - This paper presents a case of community-acquired necrotising pneumonia due to
      Panton-Valentine leukocidine-positive methicillin-susceptible Staphylococcus
      aureus and A/H1N12009 influenzavirus co-infection in a 26-year-old woman. Despite
      the presence of pejorative prognostic factors, the clinical course of the patient
      was favourable. 

PMID- 24436285
TI  - Ladakhi koilonychia.

PMID- 24436284
TI  - Decreased consciousness: bilateral thalamic infarction and its relation to the
      artery of Percheron.
AB  - This case series highlights two patients seen in the same stroke centre
      presenting with unusual symptoms. They were later diagnosed with bilateral
      thalamic infarcts, probably related to an unusual anatomical variant. The
      difficulties in establishing the diagnoses due to their relative rarity and
      complexity could have impacted on patient outcomes. 

PMID- 24436286
TI  - Forehead swelling and frontal headache: Pott's puffy tumour.

PMID- 24436287
TI  - Acting on macrocephaly in the neonatal period: an illustrative case of congenital
      teratoma.
AB  - An 11-week-old baby was brought to the paediatric emergency department by his
      mother with a 2-day history of inconsolable crying. On examination, clinical
      features of macrocephaly, separated sutures and 'sunsetting' of the eyes were
      noted. Abnormal head circumference measurements had been obtained on several
      occasions since birth, but were not acted on contrary to local guidance. During
      the emergency admission, an urgent CT scan revealed a large posterior fossa
      tumour consistent with a teratoma causing severe obstructive hydrocephalus.
      Following referral to a neurosurgical centre, emergency ventricular drainage and
      debulking surgery were performed, unfortunately with no option for cure. Distress
      to mother and baby could have been reduced with a more timely diagnosis. 

PMID- 24436288
TI  - Structure elucidation of DNA-protein crosslinks by using reductive
      desulfurization and liquid chromatography-tandem mass spectrometry.
AB  - Easier with ethyl: Guengerich and co-workers have developed a powerful new
      approach to the structure elucidation of hydrolytically stable AGT-DNA crosslinks
      by reductive desulfurization of the thioether linkage between AGT and DNA to
      convert cysteine DPCs to the corresponding ethyl-DNA adducts, which can be
      readily characterized by LC-MSn.

PMID- 24436289
TI  - "Mega" cytometry for a "mega" challenging cell type.

PMID- 24436290
TI  - How much net gain does a diagnostic imaging test provide?

PMID- 24436291
TI  - Management of recurrent and persistent metastatic lymph nodes in well
      differentiated thyroid cancer: a multifactorial decision-making guide for the
      Thyroid Cancer Care Collaborative.
AB  - BACKGROUND: Well-differentiated thyroid cancer (WDTC) recurs in up to 30% of
      patients. Guidelines from the American Thyroid Association (ATA) and the National
      Comprehensive Cancer Network (NCCN) provide valuable parameters for the
      management of recurrent disease, but fail to guide the clinician as to the
      multitude of factors that should be taken into account. The Thyroid Cancer Care
      Collaborative (TCCC) is a web-based repository of a patient's clinical
      information. Ten clinical decision-making modules (CDMMs) process this
      information and display individualized treatment recommendations. METHODS: We
      conducted a review of the literature and analysis of the management of patients
      with recurrent/persistent WDTC. RESULTS: Surgery remains the most common
      treatment in recurrent/persistent WDTC and can be performed with limited
      morbidity in experienced hands. However, careful observation may be the
      recommended course in select patients. Reoperation yields biochemical remission
      rates between 21% and 66%. There is a reported 1.2% incidence of permanent
      unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism.
      External beam radiotherapy and percutaneous ethanol ablation have been reported
      as therapeutic alternatives. Radioactive iodine as a primary therapy has been
      reported previously for metastatic lymph nodes, but is currently advocated by the
      ATA as an adjuvant to surgery. CONCLUSION: The management of recurrent lymph
      nodes is a multifactorial decision and is best determined by a multidisciplinary
      team. The CDMMs allow for easy adoption of contemporary knowledge, making this
      information accessible to both patient and clinician.

PMID- 24436292
TI  - Frequency and phase drift correction of magnetic resonance spectroscopy data by
      spectral registration in the time domain.
AB  - PURPOSE: Frequency and phase drifts are a common problem in the acquisition of in
      vivo magnetic resonance spectroscopy (MRS) data. If not accounted for, frequency
      and phase drifts will result in artifactual broadening of spectral peaks,
      distortion of spectral lineshapes, and a reduction in signal-to-noise ratio
      (SNR). We present herein a new method for estimating and correcting frequency and
      phase drifts in in vivo MRS data. METHODS: We used a simple method of fitting
      each spectral average to a reference scan (often the first average in the series)
      in the time domain through adjustment of frequency and phase terms. Due to the
      similarity with image registration, this method is referred to as "spectral
      registration." Using simulated data with known frequency and phase drifts, the
      performance of spectral registration was compared with two existing methods at
      various SNR levels. RESULTS: Spectral registration performed well in comparison
      with the other methods tested in terms of both frequency and phase drift
      estimation. CONCLUSIONS: Spectral registration provides an effective method for
      frequency and phase drift correction. It does not involve the collection of
      navigator echoes, and does not rely on any specific resonances, such as residual
      water or creatine, making it highly versatile.

PMID- 24436294
TI  - Effects of mechanical stimulation of the feet on gait and cardiovascular
      autonomic control in Parkinson's disease.
AB  - Motor impairment in Parkinson's disease (PD) is partly due to defective central
      processing of lower limb afferents. Concomitant alterations in cardiovascular
      autonomic control leading to orthostatic hypotension may worsen motor ability. We
      evaluated whether mechanical activation of feet sensory afferents could improve
      gait and modify the response of cardiovascular autonomic control to stressors in
      16 patients (age 66 +/- 2 yr) with idiopathic PD (Hoehn & Yhar scale 2-3) on
      their usual therapy. Eight subjects (group A) were randomized to undergo skin
      pressure (0.58 +/- 0.04 kg/mm(2)) stimulation at the hallux tip and first
      metatarsal joint (effective stimulation; ES) of both feet. Eight remaining
      patients (group B) underwent sham stimulation (SS) followed by ES. Three
      dimensional movement analysis provided quantitative indexes of movement
      disability before (baseline) and 24 h after ES and SS. Spectral analysis of heart
      rate and blood pressure variability provided markers of cardiac sympatho-vagal
      (LF/HF) and vascular sympathetic (LFSAP) modulations. Markers were measured at
      rest and during 75 degrees  head-up tilt, before and 24 h after ES and SS. After
      ES, step length and gait velocity increased, upright rotation velocity was
      enhanced, and step number was decreased. After ES, LFSAP declined. The increase
      in LF/HF and LFSAP induced by tilt was greater than before feet stimulation. No
      changes in gait and autonomic parameters were observed after SS. Twenty-four
      hours after ES, patients with PD showed improved gait and increased cardiac and
      vascular sympathetic modulation during upright position compared with baseline.
      Conversely, SS was ineffective on both movement and autonomic parameters,
      indicating a site specificity effect of the stimulation. 

PMID- 24436295
TI  - Eccentric exercise: acute and chronic effects on healthy and diseased tendons.
AB  - Eccentric exercise can influence tendon mechanical properties and matrix protein
      synthesis. mRNA for collagen and regulatory factors thereof are upregulated in
      animal tendons, independent of muscular contraction type, supporting the view
      that tendon, compared with skeletal muscle, is less sensitive to differences in
      type and/or amount of mechanical stimulus with regard to expression of collagen,
      regulatory factors for collagen, and cross-link regulators. In overused
      (tendinopathic) human tendon, eccentric exercise training has a beneficial
      effect, but the mechanism by which this is elicited is unknown, and slow
      concentric loading appears to have similar beneficial effects. It may be that
      tendinopathic regions, as long as they are subjected to a certain magnitude of
      load at a slow speed, independent of whether this is eccentric or concentric in
      nature, can reestablish their normal tendon fibril alignment and cell morphology.

PMID- 24436293
TI  - Rapid upregulation and clearance of distinct circulating microRNAs after
      prolonged aerobic exercise.
AB  - Short nonprotein coding RNA molecules, known as microRNAs (miRNAs), are
      intracellular mediators of adaptive processes, including muscle hypertrophy,
      contractile force generation, and inflammation. During basal conditions and
      tissue injury, miRNAs are released into the bloodstream as "circulating" miRNAs
      (c-miRNAs). To date, the impact of extended-duration, submaximal aerobic exercise
      on plasma concentrations of c-miRNAs remains incompletely characterized. We
      hypothesized that specific c-miRNAs are differentially upregulated following
      prolonged aerobic exercise. To test this hypothesis, we measured concentrations
      of c-miRNAs enriched in muscle (miR-1, miR-133a, miR-499-5p), cardiac tissue (miR
      208a), and the vascular endothelium (miR-126), as well as those important in
      inflammation (miR-146a) in healthy male marathon runners (N = 21) at rest,
      immediately after a marathon (42-km foot race), and 24 h after the race. In
      addition, we compared c-miRNA profiles to those of conventional protein
      biomarkers reflective of skeletal muscle damage, cardiac stress and necrosis, and
      systemic inflammation. Candidate c-miRNAs increased immediately after the
      marathon and declined to prerace levels or lower after 24 h of race completion.
      However, the magnitude of change for each c-miRNA differed, even when originating
      from the same tissue type. In contrast, traditional biomarkers increased after
      exercise but remained elevated 24 h postexercise. Thus c-miRNAs respond
      differentially to prolonged exercise, suggesting the existence of specific
      mechanisms of c-miRNA release and clearance not fully explained by generalized
      cellular injury. Furthermore, c-miRNA expression patterns differ in a temporal
      fashion from corollary conventional tissue-specific biomarkers, emphasizing the
      potential of c-miRNAs as unique, real-time markers of exercise-induced tissue
      adaptation. 

PMID- 24436296
TI  - Application of the [gamma-32P] ATP kinase assay to study anabolic signaling in
      human skeletal muscle.
AB  - AMPK (AMP-dependant protein kinase)-mTORC1 (mechanistic target of rapamycin in
      complex 1)-p70S6K1 (ribosomal protein S6 kinase 1 of 70 kDa) signaling plays a
      crucial role in muscle protein synthesis (MPS). Understanding this pathway has
      been advanced by the application of the Western blot (WB) technique. However,
      because many components of the mTORC1 pathway undergo numerous, multisite
      posttranslational modifications, solely studying the phosphorylation changes of
      mTORC1 and its substrates may not adequately represent the true metabolic
      signaling processes. The aim of this study was to develop and apply a
      quantitative in vitro [gamma-(32)P] ATP kinase assay (KA) for p70S6K1 to assess
      kinase activity in human skeletal muscle to resistance exercise (RE) and protein
      feeding. In an initial series of experiments the assay was validated in tissue
      culture and in p70S6K1-knockout tissues. Following these experiments, the
      methodology was applied to assess p70S6K1 signaling responses to a
      physiologically relevant stimulus. Six men performed unilateral RE followed by
      the consumption of 20 g of protein. Muscle biopsies were obtained at pre-RE, and
      1 and 3 h post-RE. In response to RE and protein consumption, p70S6K1 activity as
      assessed by the KA was significantly increased from pre-RE at 1 and 3 h post-RE.
      However, phosphorylated p70S6K1(thr389) was not significantly elevated. AMPK
      activity was suppressed from pre-RE at 3 h post-RE, whereas phosphorylated
      ACC(ser79) was unchanged. Total protein kinase B activity also was unchanged
      after RE from pre-RE levels. Of the other markers we assessed by WB,
      4EBP1(thr37/46) phosphorylation was the only significant responder, being
      elevated at 3 h post-RE from pre-RE. These data highlight the utility of the KA
      to study skeletal muscle plasticity. 

PMID- 24436297
TI  - Perturbed and spontaneous regional cerebral blood flow responses to changes in
      blood pressure after high-level spinal cord injury: the effect of midodrine.
AB  - Individuals with spinal cord injury (SCI) above the T6 spinal segment suffer from
      orthostatic intolerance. How cerebral blood flow (CBF) responds to orthostatic
      challenges in SCI is poorly understood. Furthermore, it is unclear how
      interventions meant to improve orthostatic tolerance in SCI influence CBF. This
      study aimed to examine 1) the acute regional CBF responses to rapid changes in
      blood pressure (BP) during orthostatic stress in individuals with SCI and able
      bodied (AB) individuals; and 2) the effect of midodrine (alpha1-agonist) on
      orthostatic tolerance and CBF regulation in SCI. Ten individuals with SCI >T6,
      and 10 age- and sex-matched AB controls had beat-by-beat BP and middle and
      posterior cerebral artery blood velocity (MCAv, PCAv, respectively) recorded
      during a progressive tilt-test to quantify the acute CBF response and orthostatic
      tolerance. Dynamic MCAv and PCAv to BP relationships were evaluated continuously
      in the time domain and frequency domain (via transfer function analysis). The SCI
      group was tested again after administration of 10 mg midodrine to elevate BP.
      Coherence (i.e., linearity) was elevated in SCI between BP-MCAv and BP-PCAv by
      35% and 22%, respectively, compared with AB, whereas SCI BP-PCAv gain (i.e.,
      magnitudinal relationship) was reduced 30% compared with AB (all P < 0.05). The
      acute (i.e., 0-30 s after tilt) MCAv and PCAv responses were similar between
      groups. In individuals with SCI, midodrine led to improved PCAv responses 30-60 s
      following tilt (10 +/- 3% vs. 4 +/- 2% decline; P < 0.05), and a 59% improvement
      in orthostatic tolerance (P < 0.01). The vertebrobasilar region may be
      particularly susceptible to hypoperfusion in SCI, leading to increased
      orthostatic intolerance.

PMID- 24436299
TI  - Microbubbles are detected prior to larger bubbles following decompression.
AB  - Using dual-frequency ultrasound (DFU), microbubbles (<10 MUm diameter) have been
      detected in tissue following decompression. It is not known if these microbubbles
      are the precursors for B-mode ultrasound-detectable venous gas emboli (bmdVGE).
      The purpose of this study was to determine if microbubbles could be detected
      intravascularly postdecompression and to investigate the temporal relationship
      between microbubbles and larger bmdVGE. Anesthetized swine (n = 15) were exposed
      to 4.0-4.5 ATA for 2 h, followed by decompression to 0.98 ATA. Microbubble
      presence and VGE grade were measured using DFU and B-mode ultrasound,
      respectively, before and for 1 h postdecompression, approximately every 4-5 min.
      Microbubbles appeared in the bloodstream postdecompression, both in the presence
      and absence of bmdVGE. In swine without bmdVGE, microbubbles remained elevated
      for the entire 60-min postdecompression period. In swine with bmdVGE, microbubble
      signals were detected initially but then returned to baseline. Microbubbles were
      not detected with the sham dive. Mean bmdVGE grade increased over the length of
      the postdecompression data collection period. Comparison of the two response
      curves revealed significant differences at 5 and 10 min postdecompression,
      indicating that microbubbles preceded bmdVGE. These findings indicate that
      decompression-induced microbubbles can 1) be detected intravascularly at multiple
      sites, 2) appear in the presence and absence of bmdVGE, and 3) occur before
      bmdVGE. This supports the hypothesis that microbubbles precede larger VGE
      bubbles. Microbubble presence may be an early marker of decompression stress.
      Since DFU is a low-power ultrasonic method, it may be useful for operational
      diving applications. 

PMID- 24436298
TI  - Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries.
      I. Impact of obesity.
AB  - We employed next-generation RNA sequencing (RNA-Seq) technology to determine the
      influence of obesity on global gene expression in skeletal muscle feed arteries.
      Transcriptional profiles of the gastrocnemius and soleus muscle feed arteries
      (GFA and SFA, respectively) and aortic endothelial cell-enriched samples from
      obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima
      Otsuka (LETO) rats were examined. Obesity produced 282 upregulated and 133
      downregulated genes in SFA and 163 upregulated and 77 downregulated genes in GFA
      [false discovery rate (FDR) < 10%] with an overlap of 93 genes between the
      arteries. In LETO rats, there were 89 upregulated and 114 downregulated genes in
      the GFA compared with the SFA. There were 244 upregulated and 275 downregulated
      genes in OLETF rats (FDR < 10%) in the GFA compared with the SFA, with an overlap
      of 76 differentially expressed genes common to both LETO and OLETF rats in both
      the GFA and SFA. A total of 396 transcripts were found to be differentially
      expressed between LETO and OLETF in aortic endothelial cell-enriched samples.
      Overall, we found 1) the existence of heterogeneity in the transcriptional
      profile of the SFA and GFA within healthy LETO rats, 2) that this between-vessel
      heterogeneity was markedly exacerbated in the hyperphagic, obese OLETF rat, and
      3) a greater number of genes whose expression was altered by obesity in the SFA
      compared with the GFA. Also, results indicate that in OLETF rats the GFA takes on
      a relatively more proatherogenic phenotype compared with the SFA. 

PMID- 24436300
TI  - The challenge of assessing athlete performance after altitude training.

PMID- 24436301
TI  - Computed tomographic measures of airway morphology in smokers and never-smoking
      normals.
AB  - Bronchial wall area percent (WA% = 100 * wall area/total bronchial cross
      sectional area) is a standard computed tomographic (CT) measure of central airway
      morphology utilized in smokers with chronic obstructive pulmonary disease (COPD).
      Although it provides significant clinical correlations, the range of reported WA%
      is narrow. This suggests limited macroscopic change in response to smoking or
      that remodeling proportionally affects the airway wall and lumen dimensions such
      that their ratio is preserved. The objective of this study is to assess central
      airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT
      scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai,
      and Ao were positively correlated with forced expiratory volume in 1 s (FEV1)
      expressed as a percent of predicted (FEV1%), and the WA% was negatively
      correlated with FEV1% (P < 0.0001 for all comparisons). Importantly, smokers with
      lower FEV1% tended to have airways of smaller cross-sectional area with lower WA.
      The increases in the WA% across GOLD stages of chronic obstructive pulmonary
      disease (COPD) can therefore not be due to increases in WA. The data suggest two
      possible origins for the WA% increases: 1) central airway remodeling resulting in
      overall reductions in airway caliber in excess of the decreased WA or 2) those
      with COPD had smaller native airways before they began smoking. In both cases,
      these observations provide an explanation for the limited range of values of WA%
      across stages of COPD.

PMID- 24436302
TI  - Hydrogen-bond-assisted activation of allylic alcohols for palladium-catalyzed
      coupling reactions.
AB  - We report direct activation of allylic alcohols using a hydrogen-bond-assisted
      palladium catalyst and use this for alkylation and amination reactions. The novel
      catalyst comprises a palladium complex based on a functionalized monodentate
      phosphoramidite ligand in combination with urea additives and affords linear
      alkylated and aminated allylic products selectively. Detailed kinetic analysis
      show that oxidative addition of the allyl alcohol is the rate-determining step,
      which is facilitated by hydrogen bonds between the alcohol, the ligand functional
      group, and the additional urea additive. 

PMID- 24436303
TI  - A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple
      animal and cell models of Huntington's disease.
AB  - Protein acetylation, which is central to transcriptional control as well as other
      cellular processes, is disrupted in Huntington's disease (HD). Treatments that
      restore global acetylation levels, such as inhibiting histone deacetylases
      (HDACs), are effective in suppressing HD pathology in model organisms. However,
      agents that selectively target the disease-relevant HDACs have not been
      available. SirT1 (Sir2 in Drosophila melanogaster) deacetylates histones and
      other proteins including transcription factors. Genetically reducing, but not
      eliminating, Sir2 has been shown to suppress HD pathology in model organisms. To
      date, small molecule inhibitors of sirtuins have exhibited low potency and
      unattractive pharmacological and biopharmaceutical properties. Here, we show that
      highly selective pharmacological inhibition of Drosophila Sir2 and mammalian
      SirT1 using the novel inhibitor selisistat (selisistat; 6-chloro-2,3,4,9
      tetrahydro-1H-carbazole-1-carboxamide) can suppress HD pathology caused by mutant
      huntingtin exon 1 fragments in Drosophila, mammalian cells and mice. We have
      validated Sir2 as the in vivo target of selisistat by showing that genetic
      elimination of Sir2 eradicates the effect of this inhibitor in Drosophila. The
      specificity of selisistat is shown by its effect on recombinant sirtuins in
      mammalian cells. Reduction of HD pathology by selisistat in Drosophila, mammalian
      cells and mouse models of HD suggests that this inhibitor has potential as an
      effective therapeutic treatment for human disease and may also serve as a tool to
      better understand the downstream pathways of SirT1/Sir2 that may be critical for
      HD. 

PMID- 24436304
TI  - Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of
      cartilaginous skeletal elements.
AB  - Mutations of Filamin genes, which encode actin-binding proteins, cause a wide
      range of congenital developmental malformations in humans, mainly skeletal
      abnormalities. However, the molecular mechanisms underlying Filamin functions in
      skeletal system formation remain elusive. In our screen to identify skeletal
      development molecules, we found that Cfm (Fam101) genes, Cfm1 (Fam101b) and Cfm2
      (Fam101a), are predominantly co-expressed in developing cartilage and
      intervertebral discs (IVDs). To investigate the functional role of Cfm genes in
      skeletal development, we generated single knockout mice for Cfm1 and Cfm2, as
      well as Cfm1/Cfm2 double-knockout (Cfm DKO) mice, by targeted gene disruption.
      Mice with loss of a single Cfm gene displayed no overt phenotype, whereas Cfm DKO
      mice showed skeletal malformations including spinal curvatures, vertebral fusions
      and impairment of bone growth, showing that the phenotypes of Cfm DKO mice
      resemble those of Filamin B (Flnb)-deficient mice. The number of cartilaginous
      cells in IVDs is remarkably reduced, and chondrocytes are moderately reduced in
      Cfm DKO mice. We observed increased apoptosis and decreased proliferation in Cfm
      DKO cartilaginous cells. In addition to direct interaction between Cfm and
      Filamin proteins in developing chondrocytes, we showed that Cfm is required for
      the interaction between Flnb and Smad3, which was reported to regulate Runx2
      expression. Furthermore, we found that Cfm DKO primary chondrocytes showed
      decreased cellular size and fewer actin bundles compared with those of wild-type
      chondrocytes. These results suggest that Cfms are essential partner molecules of
      Flnb in regulating differentiation and proliferation of chondryocytes and actin
      dynamics. 

PMID- 24436306
TI  - Gold-catalyzed cyclization of diynes: controlling the mode of 5-endo versus 6
      endo cyclization--an experimental and theoretical study by utilizing
      diethynylthiophenes.
AB  - Herein, a dual-gold catalyzed cyclization of 3,4-diethynylthiophenes generating
      pentaleno[c]thiophenes through gold-vinylidenes and C-H bond activation is
      disclosed. Various new heteroaromatic compounds--substrate classes unexplored to
      date--exhibiting three five-membered annulated ring systems could be synthesized
      in moderate to high yields. By comparison of the solid-state structures of the
      corresponding gold-acetylides, it could be demonstrated that the cyclization mode
      (5-endo versus 6-endo) is controlled by the electronic and not steric nature of
      the diyne backbone. Depending on different backbones, we calculated thermodynamic
      stabilities and full potential-energy surfaces giving insight into the crucial
      dual-activation cyclization step. In the case of the 3,4-thiophene backbone, in
      which the initial cyclization is rate and selectivity determining, two
      energetically distinct transition states could be localized explaining the
      observed 5-endo cyclization mode by classical transition-state theory. In the
      case of vinyl and 2,3-thiophene backbones, the theoretical analysis of the
      cyclization mode in the bifurcated cyclization area demonstrated that classical
      transition-state theory is no longer valid to explain the high experimentally
      observed selectivity. Herein, for the first time, the influence of the backbone
      and the aromatic stabilization effect of the 6-endo product in the crucial
      cyclization step could be visualized and quantified by calculating and comparing
      the full potential-energy surfaces.

PMID- 24436305
TI  - Impact of human pathogenic micro-insertions and micro-deletions on post
      transcriptional regulation.
AB  - Small insertions/deletions (INDELs) of <=21 bp comprise 18% of all recorded
      mutations causing human inherited disease and are evident in 24% of documented
      Mendelian diseases. INDELs affect gene function in multiple ways: for example, by
      introducing premature stop codons that either lead to the production of truncated
      proteins or affect transcriptional efficiency. However, the means by which they
      impact post-transcriptional regulation, including alternative splicing, have not
      been fully evaluated. In this study, we collate disease-causing INDELs from the
      Human Gene Mutation Database (HGMD) and neutral INDELs from the 1000 Genomes
      Project. The potential of these two types of INDELs to affect binding-site
      affinity of RNA-binding proteins (RBPs) was then evaluated. We identified several
      sequence features that can distinguish disease-causing INDELs from neutral
      INDELs. Moreover, we built a machine-learning predictor called PinPor (predicting
      pathogenic small insertions and deletions affecting post-transcriptional
      regulation, http://watson.compbio.iupui.edu/pinpor/) to ascertain which newly
      observed INDELs are likely to be pathogenic. Our results show that disease
      causing INDELs are more likely to ablate RBP-binding sites and tend to affect
      more RBP-binding sites than neutral INDELs. Additionally, disease-causing INDELs
      give rise to greater deviations in binding affinity than neutral INDELs. We also
      demonstrated that disease-causing INDELs may be distinguished from neutral INDELs
      by several sequence features, such as their proximity to splice sites and their
      potential effects on RNA secondary structure. This predictor showed satisfactory
      performance in identifying numerous pathogenic INDELs, with a Matthews
      correlation coefficient (MCC) value of 0.51 and an accuracy of 0.75. 

PMID- 24436307
TI  - A new bacterial chemical signal: mapping the chemical space used for
      communication.
AB  - Sticking together: genetic information, bioassays and chemical characterisation
      have revealed that photopyrones produced by insect pathogenic Photorabdus
      bacteria are new bacterial signalling compounds. They induce cell clumping
      behaviour in the bacterium.

PMID- 24436308
TI  - Eight color immunophenotyping of T-, B- and NK-cell subpopulations for
      characterization of chronic immunodeficiencies.
AB  - Background: The heterogeneity of primary and secondary immunodeficiencies demands
      for the development of a comprehensive flow cytometric screening system, based on
      reference values that support a standardized immunophenotypic characterization of
      most lymphocyte subpopulations. Methods: Peripheral blood samples from healthy
      adult volunteers (n=25) were collected and split into eight panel fractions
      (100ul each). Subsequently, pre-mixed 8-color antibody cocktails were incubated
      per specific panel of whole blood to detect and differentiate cell subsets of:
      (i) a general lymphocyte overviews, (ii) B-cell subpopulations, (iii) CD4+
      subpopulations, (iv) CD8+ subpopulations, (v) regulatory T-cells, (vi) recent
      thymic emigrants, (vii) NK-cell subpopulations, (viii) NK-cell activation
      markers. All samples were lysed, washed and measured by flow cytometry. FACS DIVA
      software was used for data analysis and calculation of quadrant statistics (mean
      values, standard error of mean, percentile ranges). Results: Whole blood staining
      of lymphocytes provided the analysis of: (i) CD3+, 4+, 8+, 19+, 16/56+, and
      activated CD4/8 cells; (ii) immature, naive, non-switched/switched, memory,
      (activated) CD21low , transitional B-cells, plasmablasts/plasmacells; (iii and
      iv) naive, central memory, effector, effector memory, TH1/TH2/TH17-like and
      CCR5+CD8-cells; (v) CD25+, regulatory T-cells (naive/memory, HLA-DR+); (vi)
      alpha/beta- and gamma/delta-T-cells, recent thymic emigrants in CD4/CD8 cells;
      (vii) immature/mature CD56bright , CD94/NKG2D+ NK-cells; and (viii) Nkp30, 44, 46
      and CD57+NK-cells. Clinical examples and quadrant statistics are provided.
      Conclusion: The present study represents a practical approach to standardize the
      immunophenotyping of most T-, B- and NK-cell subpopulations. That allows
      differentiating, whether abnormalities or developmental shifts observed in
      lymphocyte subpopulations originates either from primary or secondary
      immunological disturbance. (c) 2014 Clinical Cytometry Society.

PMID- 24436309
TI  - Validation of a semiautomated spinal cord segmentation method.
AB  - PURPOSE: To validate semiautomated spinal cord segmentation in healthy subjects
      and patients with neurodegenerative diseases and trauma. MATERIALS AND METHODS:
      Forty-nine healthy subjects, as well as 29 patients with amyotrophic lateral
      sclerosis, 19 with spinal muscular atrophy, and 14 with spinal cord injuries were
      studied. Cord area was measured from T2 -weighted 3D turbo spin echo images (cord
      levels from C2 to T9) using the semiautomated segmentation method of Losseff et
      al (Brain [1996] 119(Pt 3):701-708), compared with manual segmentation.
      Reproducibility was evaluated using the inter- and intraobserver coefficient of
      variation (CoV). Accuracy was assessed using the Dice similarity coefficient
      (DSC). Robustness to initialization was assessed by simulating modifications to
      the contours drawn manually prior to segmentation. RESULTS: Mean interobserver
      CoV was 4.00% for manual segmentation (1.90% for Losseff's method) in the
      cervical region and 5.62% (respectively 2.19%) in the thoracic region. Mean
      intraobserver CoV was 2.34% for manual segmentation (1.08% for Losseff's method)
      in the cervical region and 2.35% (respectively 1.34%) in the thoracic region. DSC
      was high (0.96) in both cervical and thoracic regions. DSC remained higher than
      0.8 even when modifying initial contours by 50%. CONCLUSION: The semiautomated
      segmentation method showed high reproducibility and accuracy in measuring spinal
      cord area.

PMID- 24436310
TI  - Ultrahigh PEMFC performance of a thin-film, dual-electrode assembly with tailored
      electrode morphology.
AB  - A dual-electrode membrane electrode assembly (MEA) for proton exchange membrane
      fuel cells with enhanced polarization under zero relative humidity (RH) is
      fabricated by introducing a phase-separated morphology in an agglomerated
      catalyst layer of Pt/C (platinum on carbon black) and Nafion. In the catalyst
      layer, a sufficient level of phase separation is achieved by dispersing the Pt
      catalyst and the Nafion dispersion in a mixed-solvent system (propane-1,2,3
      triol/1-methyl-2-pyrrolidinone).The high polymer chain mobility results in
      improved water uptake and regular pore-size distribution with small pore
      diameters. The electrochemical performance of the dual-film electrode assembly
      with different levels of phase separation is compared to conventional electrode
      assemblies. As a result, good performance at 0 % RH is obtained because self
      humidification is dramatically improved by attaching this dense and phase
      separated catalytic overlayer onto the conventional catalyst layer. A MEA
      prepared using the thin-film, dual-layered electrode exhibits 39-fold increased
      RH stability and 28-fold improved start-up recovery time during the on-off
      operation relative to the conventional device. We demonstrate the successful
      operation of the dual-layered electrode comprised of discriminatively phase
      separated agglomerates with an ultrahigh zero RH fuel-cell performance reaching
      over 95 % performance of a fully humidified MEA.

PMID- 24436311
TI  - New insights into the molecular pathogenesis of langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a rare proliferative disorder
      characterized by an accumulation of cells sharing the major phenotypic features
      of cutaneous Langerhans cells. Given its variable clinical evolution, ranging
      from self-limiting lesions to multisystemic forms with a poor prognosis, in the
      last decades it has been debated whether LCH might not have a neoplastic rather
      than an inflammatory nature. However, although the fundamental events underlying
      the pathogenesis of LCH are still elusive, recent advances have strikingly
      improved our understanding of the disease. In particular, the identification of
      multiple interplays between LCH cells and their tumor microenvironment, along
      with the recognition of the lesional cytokine storm as a key determinant of LCH
      progression, has substantiated new opportunities for devising targeted
      therapeutic approaches. Strikingly, the detection of the rapidly accelerated
      fibrosarcoma isoform B(V600E) gain-of-function mutation as a genetic alteration
      recurring in more than 50% of patients has fueled the paradoxical picture of LCH
      as a tumor of the antigen-presenting cells that can evade rejection by the immune
      system. Thus, new evidence regarding the ontogeny of LCH cells, as well as a
      better understanding of the putative immune system frustrating strategy in LCH,
      may help to define the precise pathogenesis. 

PMID- 24436313
TI  - Touching the other's suffering: cross-cultural challenges in palliative treatment
      along geopolitical crossroads.

PMID- 24436312
TI  - Human epidermal growth factor receptor family-targeted therapies in the treatment
      of HER2-overexpressing breast cancer.
AB  - Breast cancer characterized by overexpression of human epidermal growth factor
      receptor 2 (HER2) has been associated with more aggressive disease progression
      and a poorer prognosis. Although an improved understanding of breast cancer
      pathogenesis and the role of HER2 signaling has resulted in significant survival
      improvements in the past 20 years, resistance to HER2-targeted therapy remains a
      concern. A number of strategies to prevent or overcome resistance to HER2
      targeted therapy in breast cancer are being evaluated. This article provides a
      comprehensive review of (a) the role of HER2 signaling in breast cancer
      pathogenesis, (b) potential receptor and downstream therapeutic targets in breast
      cancer to overcome resistance to HER2-targeted therapy, and (c) clinical trials
      evaluating agents targeting one or more members of the HER family and/or
      downstream pathways for the treatment of breast cancer, with a focus on
      metastatic disease. 

PMID- 24436314
TI  - Richardson-Lucy deconvolution as a general tool for combining images with
      complementary strengths.
AB  - We use Richardson-Lucy (RL) deconvolution to combine multiple images of a
      simulated object into a single image in the context of modern fluorescence
      microscopy techniques. RL deconvolution can merge images with very different
      point-spread functions, such as in multiview light-sheet microscopes,1, 2 while
      preserving the best resolution information present in each image. We show that RL
      deconvolution is also easily applied to merge high-resolution, high-noise images
      with low-resolution, low-noise images, relevant when complementing conventional
      microscopy with localization microscopy. We also use RL deconvolution to merge
      images produced by different simulated illumination patterns, relevant to
      structured illumination microscopy (SIM)3, 4 and image scanning microscopy (ISM).
      The quality of our ISM reconstructions is at least as good as reconstructions
      using standard inversion algorithms for ISM data, but our method follows a
      simpler recipe that requires no mathematical insight. Finally, we apply RL
      deconvolution to merge a series of ten images with varying signal and resolution
      levels. This combination is relevant to gated stimulated-emission depletion
      (STED) microscopy, and shows that merges of high-quality images are possible even
      in cases for which a non-iterative inversion algorithm is unknown. 

PMID- 24436315
TI  - Human bone reactions around implants with adverse interfacial bone strain over 20
      years.
AB  - AIMS: It has been accepted that bone damage and subsequent resorption occurs in
      cases of adverse interfacial bone strain. Fractured implants represents an
      important opportunity for evaluating the bone response to overstrain. The
      objective of the study was to analyze the bone morphology and morphometry around
      retrieved fractured implants in humans. Five fractured implants retrieved after
      22.4 (+/- 2.8) years were used in the present study. The investigation was
      conducted in a transmitted brightfield and circularly polarized light Microscope.
      The parameters considered were the total bone area, total bone remodeling area,
      bone-remodeling rate (BRR), and bone transverse collagen fibers orientation
      (CFO). FINDINGS: For grouped samples, the BRR was 51.9% (+/- 10) while the
      transverse CFO was 13.0% (+/- 9.7). The interthread BRR was 58.1% (+/- 4.0) for
      level 1 and 40.4% (+/- 12.8) for level 2 with a significant decrease in BRR (p =
      0.019) as a function of depth along the implant length. CONCLUSIONS: Both bone
      level and bone quality attains stability to a certain level with respect to
      implant neck fracture following physiologic interaction between mechanical and
      biological inputs. The BRR significantly decrease as function of threads depth.

PMID- 24436316
TI  - The non-linear threshold association between aspirin use and esophageal
      adenocarcinoma: results of a dose-response meta-analysis.
AB  - BACKGROUND: The role of aspirin use in chemoprevention of esophageal
      adenocarcinoma (EAC) is still unclear. Previous meta-analyses have reported a
      beneficial effect of aspirin use, whereas it remains still under debate whether
      there are non-linear frequency-risk and duration-risk relations, such as a
      "threshold" effect. METHODS: Nine observational studies reporting the association
      between aspirin use and EAC risk were selected through a combined search with the
      PUBMED and EMBASE electronic databases of articles published before June 2013.
      Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using
      fixed-effects models, and the cubic spline regression models were performed for
      the study of frequency-risk and duration-risk relations. RESULTS: A monotonically
      decreasing relation was observed only for <= 4.5 times per week (OR=0.75, 95%CI
      0.64-0.88, for twice per week; OR=0.59, 95%CI 0.45-0.78, for 4.5 times per week)
      and <= 6 years (OR=0.82, 95%CI 0.76-0.91, for 1 year; OR=0.53, 95%CI 0.37-0.75,
      for 3 years) of aspirin use using the non-users as the reference. Once the
      frequency is more than 4.5 times/week or the duration is longer than 6 years, no
      further benefit was observed. CONCLUSION: Our findings suggest that there may be
      non-linear threshold relations of frequency and duration of aspirin use with the
      risk of EAC. Further data from randomized clinical trials are required.

PMID- 24436317
TI  - Twelve-year weight change, waist circumference change and incident obesity: the
      Australian diabetes, obesity and lifestyle study.
AB  - OBJECTIVE: This study aimed to describe the changes in weight and waist
      circumference (WC), examine the incidence of obesity as defined by body mass
      index (BMI) and WC, and describe the changes in the prevalence of obesity over 12
      years. METHODS: In 1999/2000, 11,247 adults aged >=25 years were recruited from
      42 randomly selected areas across Australia. In total, 44.6% of eligible
      participants completed follow-up in 2011/12. Height, weight, and WC were measured
      at both surveys. RESULTS: People who were 25-34 years of age at baseline gained
      an average of 6.7 kg weight and 6.6 cm WC, whereas those aged >=75 years lost an
      average of 4.5 kg and gained an average of 0.8 cm. Women had a greater increase
      in WC than men, but did not differ in terms of weight gain. The 12-year incidence
      of obesity was 15.0% when defined by BMI and 31.8% when defined by WC. According
      to BMI and WC combined, the percentage of the cohort that was normal weight
      decreased from 33 to 21% and the percentage that was obese increased from 32 to
      49% between baseline and 2012. CONCLUSIONS: In addition to BMI, assessment of WC
      should be incorporated more frequently when assessing population trends of
      obesity and the burden of disease associated with excess adiposity.

PMID- 24436318
TI  - Parametric Coding of the Size and Clutter of Natural Scenes in the Human Brain.
AB  - Estimating the size of a space and its degree of clutter are effortless and
      ubiquitous tasks of moving agents in a natural environment. Here, we examine how
      regions along the occipital-temporal lobe respond to pictures of indoor real
      world scenes that parametrically vary in their physical "size" (the spatial
      extent of a space bounded by walls) and functional "clutter" (the organization
      and quantity of objects that fill up the space). Using a linear regression model
      on multivoxel pattern activity across regions of interest, we find evidence that
      both properties of size and clutter are represented in the patterns of
      parahippocampal cortex, while the retrosplenial cortex activity patterns are
      predominantly sensitive to the size of a space, rather than the degree of
      clutter. Parametric whole-brain analyses confirmed these results. Importantly,
      this size and clutter information was represented in a way that generalized
      across different semantic categories. These data provide support for a property
      based representation of spaces, distributed across multiple scene-selective
      regions of the cerebral cortex. 

PMID- 24436319
TI  - Maturation of Cortico-Subcortical Structural Networks-Segregation and Overlap of
      Medial Temporal and Fronto-Striatal Systems in Development.
AB  - The brain consists of partly segregated neural circuits within which structural
      convergence and functional integration occurs during development. The
      relationship of structural cortical and subcortical maturation is largely
      unknown. We aimed to study volumetric development of the hippocampus and basal
      ganglia (caudate, putamen, pallidum, accumbens) in relation to volume changes
      throughout the cortex. Longitudinal MRI data were obtained across a mean interval
      of 2.6 years in 85 participants with an age range of 8-19 years at study start.
      Left and right subcortical changes were related to cortical change vertex-wise in
      the ipsilateral hemisphere with general linear models with age, sex, interval
      between scans, and mean cortical volume change as covariates. Hippocampal
      cortical change relationships centered on parts of the Papez circuit, including
      entorhinal, parahippocampal, and isthmus cingulate areas, and lateral temporal,
      insular, and orbitofrontal cortices in the left hemisphere. Basal ganglia
      cortical change relationships were observed in mostly nonoverlapping and more
      anterior cortical areas, all including the anterior cingulate. Other patterns
      were unique to specific basal ganglia structures, including pre-, post-, and
      paracentral patterns relating to putamen change. In conclusion, patterns of
      cortico-subcortical development as assessed by morphometric analyses in part map
      out segregated neural circuits at the macrostructural level. 

PMID- 24436320
TI  - Laterality Differences in Cerebellar-Motor Cortex Connectivity.
AB  - Lateralization of function is an important organizational feature of the motor
      system. Each effector is predominantly controlled by the contralateral cerebral
      cortex and the ipsilateral cerebellum. Transcranial magnetic stimulation studies
      have revealed hemispheric differences in the stimulation strength required to
      evoke a muscle response from the primary motor cortex (M1), with the dominant
      hemisphere typically requiring less stimulation than the nondominant. The current
      study assessed whether the strength of the connection between the cerebellum and
      M1 (CB-M1), known to change in association with motor learning, have hemispheric
      differences and whether these differences have any behavioral correlate. We
      observed, in right-handed individuals, that the connection between the right
      cerebellum and left M1 is typically stronger than the contralateral network.
      Behaviorally, we detected no lateralized learning processes, though we did find a
      significant effect on the amplitude of reaching movements across hands.
      Furthermore, we observed that the strength of the CB-M1 connection is correlated
      with the amplitude variability of reaching movements, a measure of movement
      precision, where stronger connectivity was associated with better precision.
      These findings indicate that lateralization in the motor system is present beyond
      the primary motor cortex, and points to an association between cerebellar M1
      connectivity and movement execution. 

PMID- 24436321
TI  - Transient Maternal Hypothyroxinemia Potentiates the Transcriptional Response to
      Exogenous Thyroid Hormone in the Fetal Cerebral Cortex Before the Onset of Fetal
      Thyroid Function: A Messenger and MicroRNA Profiling Study.
AB  - Thyroid hormone (TH) is essential for brain development both before and after
      birth. We have used gene expression microarrays to identify TH-regulated genes in
      the fetal cerebral cortex prior to the onset of fetal thyroid function to better
      understand the role of TH in early cortical development. TH levels were
      transiently manipulated in pregnant mice by treatment with goitrogens from
      gestational day (GD) 13-16 and/or by injection of TH 12 h before sacrifice on GD
      16. The transcriptional response to exogenous TH in the GD 16 fetal cortex was
      potentiated by transient goitrogen treatment, suggesting that the
      hypothyroxinemic brain is a different substrate upon which TH can act, or that
      robust compensatory mechanisms are induced by transient hypothyroxinemia. Several
      known TH-responsive genes were identified including Klf9, and several novel TH
      responsive genes such as Appbp2, Ppap2b, and Fgfr1op2 were identified in which TH
      response elements were confirmed. We also identified specific microRNAs whose
      expression in the fetal cortex was affected by TH treatment, and determined that
      Ppap2b and Klf9 are the target genes of miR-16 and miR-106, respectively. Thus, a
      complex redundant functional network appears to coordinate TH-mediated gene
      expression in the developing brain. 

PMID- 24436322
TI  - Morning surge in blood pressure is associated with reactivity of the sympathetic
      nervous system.
AB  - BACKGROUND: An exaggerated morning surge in blood pressure (BP) closely relates
      to target organ damage and cardiovascular risk, but whether the causative
      mechanism involves greater reactivity of the sympathetic nervous system (SNS) is
      unknown. We determined whether the response of the SNS to a cold pressor test
      predicted the BP morning surge. METHODS: Ambulatory BP recordings were obtained
      from 14 men and 19 women (age = 41+/-4 years), and the amplitude (day-night
      difference), rate of rise (RoR), rate by amplitude product (BPPower), and morning
      BP surge (MBPS; post-awake minus pre-awake) of morning mean arterial pressure
      (MAP) were determined. The reactivity of the SNS to CPT was assessed by recording
      of muscle sympathetic nerve activity (MSNA). RESULTS: CPT induced a marked
      increase in MAP and all parameters of MSNA, including burst amplitude. Log
      normalized BPPower positively correlated with the overall average CPT-induced
      increases in total MSNA (r = 0.38; P = 0.04) and burst amplitude (r = 0.43; P =
      0.02) but was not related to the increase in MSNA frequency. Furthermore, a
      strong positive linear trend in the CPT-induced changes in burst amplitude across
      tertiles of BPPower and RoR was observed. BPPower and RoR were not related to CPT
      induced hemodynamic changes. The MBPS did not correlate with any of the CPT
      induced changes in vascular or MSNA variables. CONCLUSIONS: These results suggest
      that the central nervous system mechanisms influencing the increase in MSNA burst
      amplitude during arousal may also be fundamental in determining the rate and
      power of BP rise during the morning period.

PMID- 24436323
TI  - Obstructive sleep apnea syndrome is associated with higher diastolic blood
      pressure in men but not in women.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) and poor sleep quality both
      increase blood pressure (BP). This study aimed to find the sex effects and the
      role of poor sleep quality on systolic BP (SBP) and diastolic BP (DBP) in OSAS
      patients. METHODS: Polysomnographic findings, morning BP values, and clinical
      data of 460 subjects (348 men; 112 women) diagnosed with OSAS were analyzed.
      Analyses were performed separately in each sex to examine the association of the
      apnea-hypopnea index (AHI) with BP, SBP, DBP, and sleep quality. RESULTS: In male
      subjects, AHI predicted the high BP and high DBP groups but not the high SBP
      group. In female subjects, AHI did not predict any of the high BP, DBP, or SBP
      groups. Poor sleep quality, in the absence of AHI effect, weakly correlated with
      BP in both sexes, but the association between poor sleep quality and high AHI was
      stronger in male subjects than in females. CONCLUSIONS: In male subjects only,
      OSAS was associated with DBP but not SBP. The significant association between
      OSAS and DBP may be responsible for the BP elevations in OSAS. It could be
      speculated that the stronger association between poor sleep quality and OSAS in
      male subjects compared with females may have partly contributed to the sex effect
      on BP.

PMID- 24436324
TI  - Methylglyoxal, a reactive glucose metabolite, increases renin angiotensin
      aldosterone and blood pressure in male Sprague-Dawley rats.
AB  - BACKGROUND: The majority of people with diabetes develop hypertension along with
      increased activity of the renin-angiotensin system. Methylglyoxal, a reactive
      glucose metabolite, is elevated in diabetic patients. We investigated the effects
      of methylglyoxal on the renin-angiotensin system and blood pressure. METHODS:
      Male Sprague-Dawley rats were treated with a continuous infusion of methylglyoxal
      with a minipump for 4 weeks. Organs/tissues and cultured vascular smooth muscle
      cells (VSMCs) were used for molecular studies. High-performance liquid
      chromatography, Western blotting, and quantitative real-time polymerase chain
      reaction were used to measure methylglyoxal, proteins, and mRNA, respectively.
      Small interfering RNA for angiotensinogen and the receptor for advanced glycation
      endproducts (RAGE) were used to study mechanisms. RESULTS: Methylglyoxal-treated
      rats developed a significant increase in blood pressure and plasma levels of
      aldosterone, renin, angiotensin, and catecholamines. Methylglyoxal level and
      protein and mRNA for angiotensin, AT1 receptor, adrenergic alpha1D receptor, and
      renin were significantly increased in the aorta and/or kidney of methylglyoxal
      treated rats, a novel finding. Alagebrium attenuated the above effects of
      methylgloyxal. Treatment of cultured VSMCs with methylglyoxal or high glucose (25
      mM) significantly increased cellular methylglyoxal and protein and mRNA for
      nuclear factor kappa B (NF-kappaB), angiotensin, AT1 receptor, and alpha1D
      receptor, which were prevented by inhibition of NF-kappaB, and by alagebrium.
      Silencing of mRNA for RAGE prevented the increase in NF-kB induced by
      methylglyoxal. Silencing of mRNA for angiotensinogen prevented the increase in NF
      kappaB, angiotensin, AT1 receptor, and alpha1D receptor. CONCLUSIONS:
      Methylglyoxal activates NF-kappaB through RAGE and thereby increases renin
      angiotensin levels, a novel finding, and a probable mechanism of increase in
      blood pressure.

PMID- 24436325
TI  - Association of renin and aldosterone with ethnicity and blood pressure: the Multi
      Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Although variations in plasma renin activity (PRA) and aldosterone
      have been examined in whites and blacks, the association of these hormones with
      blood pressure in multiethnic populations has not been described. METHODS: We
      measured PRA and aldosterone in 1,021 participants in the Multi-Ethnic Study of
      Atherosclerosis not taking antihypertensives and examined the association between
      ethnicity and PRA/aldosterone and the association between PRA/aldosterone with
      systolic blood pressure (SBP). RESULTS: Average age was 62 (SD = 9) years, and
      49% of participants were women. Median PRA was 0.51 (interquartile range (IQR) =
      0.29-0.87) ng/ml/hour, and median aldosterone was 12.6 (IQR = 9.1-17.1) ng/dl.
      After age and sex adjustment, compared with whites, blacks had 28% lower PRA and
      17.4% lower aldosterone, and Hispanics had 20.1% higher PRA but similar
      aldosterone levels. After multivariable adjustment, compared with whites, only
      Hispanic ethnicity independently associated with higher PRA (0.18ng/ml/hour; 95%
      confidence interval (CI) = 0.06-0.31). Blacks had lower aldosterone (-1.7ng/dl;
      95% CI = -3.2 to -0.2) compared with whites. After multivariable adjustment, PRA
      was associated with lower SBP in whites (-3.2mm Hg; 95% CI = -5.2 to -1.2 per
      standardized unit PRA), Chinese (-3.5mm Hg; 95% CI = -6.2 to -0.80 per
      standardized unit), and Hispanics (-2.3mm Hg; 95% CI = -4.1 to -0.6 per
      standardized unit) but not blacks. Aldosterone was associated with higher SBP
      only in Hispanics (2.5mm Hg; 95% CI = 0.4-4.5 per SD). CONCLUSIONS: Compared with
      whites, blacks have lower aldosterone and Hispanics have higher PRA. Aldosterone
      had significant associations with higher SBP in Hispanics compared with other
      groups, a finding that may suggest a different mechanism of hypertension.

PMID- 24436326
TI  - Statin therapy, fitness, and mortality risk in middle-aged hypertensive male
      veterans.
AB  - BACKGROUND: Hypertension often coexists with dyslipidemia, accentuating
      cardiovascular risk. Statins are often prescribed in hypertensive individuals to
      lower cardiovascular risk. Higher fitness is associated with lower mortality, but
      exercise capacity may be attenuated in hypertension. The combined effects of
      fitness and statin therapy in hypertensive individuals have not been assessed.
      Thus, we assessed the combined health benefits of fitness and statin therapy in
      hypertensive male subjects. METHODS: Peak exercise capacity was assessed in
      10,202 hypertensive male subjects (mean age = 60.4 +/- 10.6 years) in 2 Veterans
      Affairs Medical Centers. We established 4 fitness categories based on peak
      metabolic equivalents (METs) achieved and 8 categories based on fitness status
      and statin therapy. RESULTS: During the follow-up period (median = 10.2 years),
      there were 2,991 deaths. Mortality risk was 34% lower (hazard ratio (HR) = 0.66;
      95% confidence interval (CI) = 0.59-0.74; P < 0.001) among individuals treated
      with statins compared with those not on statins. The fitness-related mortality
      risk association was inverse and graded regardless of statin therapy status. Risk
      reduction associated with exercise capacity of 5.1-8.4 METs was similar to that
      observed with statin therapy. However, those achieving >=8.5 METs had 52% lower
      risk (HR = 0.48; 95% CI = 0.37-0.63) when compared with the least-fit subjects
      (<=5 METs) on statin therapy. CONCLUSIONS: The combination of statin therapy and
      higher fitness lowered mortality risk in hypertensive individuals more
      effectively than either alone. The risk reduction associated with moderate
      increases in fitness was similar to that achieved by statin therapy. Higher
      fitness was associated with 52% lower mortality risk when compared with the least
      fit subjects on statin therapy.

PMID- 24436327
TI  - A case report of subacute bronchial toxicity induced by an electronic cigarette.

PMID- 24436328
TI  - Answer to 'COPD and IPF: it's all about regulation and balance'.

PMID- 24436329
TI  - Conformational heterogeneity in antibody-protein antigen recognition:
      implications for high affinity protein complex formation.
AB  - Specific, high affinity protein-protein interactions lie at the heart of many
      essential biological processes, including the recognition of an apparently
      limitless range of foreign proteins by natural antibodies, which has been
      exploited to develop therapeutic antibodies. To mediate biological processes,
      high affinity protein complexes need to form on appropriate, relatively rapid
      timescales, which presents a challenge for the productive engagement of complexes
      with large and complex contact surfaces (~600-1800 A(2)). We have obtained
      comprehensive backbone NMR assignments for two distinct, high affinity antibody
      fragments (single chain variable and antigen-binding (Fab) fragments), which
      recognize the structurally diverse cytokines interleukin-1beta (IL-1beta, beta
      sheet) and interleukin-6 (IL-6, alpha-helical). NMR studies have revealed that
      the hearts of the antigen binding sites in both free anti-IL-1beta Fab and anti
      IL-6 single chain variable exist in multiple conformations, which interconvert on
      a timescale comparable with the rates of antibody-antigen complex formation. In
      addition, we have identified a conserved antigen binding-induced change in the
      orientation of the two variable domains. The observed conformational
      heterogeneity and slow dynamics at protein antigen binding sites appears to be a
      conserved feature of many high affinity protein-protein interfaces structurally
      characterized by NMR, suggesting an essential role in protein complex formation.
      We propose that this behavior may reflect a soft capture, protein-protein docking
      mechanism, facilitating formation of high affinity protein complexes on a
      timescale consistent with biological processes. 

PMID- 24436330
TI  - Comprehensive cysteine-scanning mutagenesis reveals Claudin-2 pore-lining
      residues with different intrapore locations.
AB  - The first extracellular loop (ECL1) of claudins forms paracellular pores in the
      tight junction that determine ion permselectivity. We aimed to map the pore
      lining residues of claudin-2 by comprehensive cysteine-scanning mutagenesis of
      ECL1. We screened 45 cysteine mutations within the ECL1 by expression in
      polyclonal Madin-Darby canine kidney II Tet-Off cells and found nine mutants that
      displayed a significant decrease of conductance after treatment with the thiol
      reactive reagent 2-(trimethylammonium)ethyl methanethiosulfonate, indicating the
      location of candidate pore-lining residues. Next, we stably expressed these
      candidates in monoclonal Madin-Darby canine kidney I Tet-Off cells and exposed
      them to thiol-reactive reagents. The maximum degree of inhibition of conductance,
      size selectivity of degree of inhibition, and size dependence of the kinetics of
      reaction were used to deduce the location of residues within the pore. Our data
      support the following sequence of pore-lining residues located from the narrowest
      to the widest part of the pore: Ser(68), Ser(47), Thr(62)/Ile(66), Thr(56),
      Thr(32)/Gly(45), and Met(52). The paracellular pore appears to primarily be lined
      by polar side chains, as expected for a predominantly aqueous environment.
      Furthermore, our results strongly suggest the existence of a continuous sequence
      of residues in the ECL1 centered around Asp(65)-Ser(68) that form a major part of
      the lining of the pore. 

PMID- 24436331
TI  - Assessment of myeloperoxidase activity by the conversion of hydroethidine to 2
      chloroethidium.
AB  - Oxidants derived from myeloperoxidase (MPO) contribute to inflammatory diseases.
      In vivo MPO activity is commonly assessed by the accumulation of 3-chlorotyrosine
      (3-Cl-Tyr), although 3-Cl-Tyr is formed at low yield and is subject to
      metabolism. Here we show that MPO activity can be assessed using hydroethidine
      (HE), a probe commonly employed for the detection of superoxide. Using LC/MS/MS,
      (1)H NMR, and two-dimensional NOESY, we identified 2-chloroethidium (2-Cl-E(+))
      as a specific product when HE was exposed to hypochlorous acid (HOCl),
      chloramines, MPO/H2O2/chloride, and activated human neutrophils. The rate
      constant for HOCl-mediated conversion of HE to 2-Cl-E(+) was estimated to be 1.5
      * 10(5) M(-1)s(-1). To investigate the utility of 2-Cl-E(+) to assess MPO
      activity in vivo, HE was injected into wild-type and MPO-deficient (Mpo(-/-))
      mice with established peritonitis or localized arterial inflammation, and tissue
      levels of 2-Cl-E(+) and 3-Cl-Tyr were then determined by LC/MS/MS. In wild-type
      mice, 2-Cl-E(+) and 3-Cl-Tyr were detected readily in the peritonitis model,
      whereas in the arterial inflammation model 2-Cl-E(+) was present at comparatively
      lower concentrations (17 versus 0.3 pmol/mg of protein), and 3-Cl-Tyr could not
      be detected. Similar to the situation with 3-Cl-Tyr, tissue levels of 2-Cl-E(+)
      were decreased substantially in Mpo(-/-) mice, indicative of the specificity of
      the assay. In the arterial inflammation model, 2-Cl-E(+) was absent from non
      inflamed arteries and blood, suggesting that HE oxidation occurred locally in the
      inflamed artery. Our data suggest that the conversion of exogenous HE to 2-Cl
      E(+) may be a useful selective and sensitive marker for MPO activity in addition
      to 3-Cl-Tyr.

PMID- 24436332
TI  - The ATP sites of AAA+ clamp loaders work together as a switch to assemble clamps
      on DNA.
AB  - Clamp loaders belong to a family of proteins known as ATPases associated with
      various cellular activities (AAA+). These proteins utilize the energy from ATP
      binding and hydrolysis to perform cellular functions. The clamp loader is
      required to load the clamp onto DNA for use by DNA polymerases to increase
      processivity. ATP binding and hydrolysis are coordinated by several key residues,
      including a conserved Lys located within the Walker A motif (or P-loop). This
      residue is required for each subunit to bind ATP. The specific function of each
      ATP molecule bound to the Saccharomyces cerevisiae clamp loader is unknown. A
      series of point mutants, each lacking a single Walker A Lys residue, was
      generated to study the effects of abolishing ATP binding in individual clamp
      loader subunits. A variety of biochemical assays were used to analyze the
      function of ATP binding during discrete steps of the clamp loading reaction. All
      mutants reduced clamp binding/opening to different degrees. Decreased clamp
      binding activity was generally correlated with decreases in the population of
      open clamps, suggesting that differences in the binding affinities of Walker A
      mutants stem from differences in stabilization of proliferating cell nuclear
      antigen in an open conformation. Walker A mutations had a smaller effect on DNA
      binding than clamp binding/opening. Our data do not support a model in which each
      ATP site functions independently to regulate a different step in the clamp
      loading cycle to coordinate these steps. Instead, the ATP sites work in unison to
      promote conformational changes in the clamp loader that drive clamp loading. 

PMID- 24436333
TI  - Central cavity of fructose-1,6-bisphosphatase and the evolution of AMP/fructose
      2,6-bisphosphate synergism in eukaryotic organisms.
AB  - The effects of AMP and fructose 2,6-bisphosphate (Fru-2,6-P2) on porcine fructose
      1,6-bisphosphatase (pFBPase) and Escherichia coli FBPase (eFBPase) differ in
      three respects. AMP/Fru-2,6-P2 synergism in pFBPase is absent in eFBPase. Fru-2,6
      P2 induces a 13 degrees  subunit pair rotation in pFBPase but no rotation in
      eFBPase. Hydrophilic side chains in eFBPase occupy what otherwise would be a
      central aqueous cavity observed in pFBPase. Explored here is the linkage of
      AMP/Fru-2,6-P2 synergism to the central cavity and the evolution of synergism in
      FBPases. The single mutation Ser(45) -> His substantially fills the central
      cavity of pFBPase, and the triple mutation Ser(45) -> His, Thr(46) -> Arg, and
      Leu(186) -> Tyr replaces porcine with E. coli type side chains. Both single and
      triple mutations significantly reduce synergism while retaining other wild-type
      kinetic properties. Similar to the effect of Fru-2,6-P2 on eFBPase, the triple
      mutant of pFBPase with bound Fru-2,6-P2 exhibits only a 2 degrees  subunit pair
      rotation as opposed to the 13 degrees  rotation exhibited by the Fru-2,6-P2
      complex of wild-type pFBPase. The side chain at position 45 is small in all
      available eukaryotic FBPases but large and hydrophilic in bacterial FBPases,
      similar to eFBPase. Sequence information indicates the likelihood of synergism in
      the FBPase from Leptospira interrogans (lFBPase), and indeed recombinant lFBPase
      exhibits AMP/Fru-2,6-P2 synergism. Unexpectedly, however, AMP also enhances Fru-6
      P binding to lFBPase. Taken together, these observations suggest the evolution of
      AMP/Fru-2,6-P2 synergism in eukaryotic FBPases from an ancestral FBPase having a
      central aqueous cavity and exhibiting synergistic feedback inhibition by AMP and
      Fru-6-P.

PMID- 24436336
TI  - Letter from the editor: a new home for the Journal of Child Neurology.

PMID- 24436334
TI  - Evaluation of commercial HPV assays in the context of post-treatment follow-up:
      Scottish Test of Cure Study (STOCS-H).
AB  - AIMS: Human papillomavirus (HPV) testing is more sensitive than cytology for
      detection of residual/recurrent cervical disease after lesion treatment. Several
      HPV test comparison studies have been performed within triage and screening
      populations, but data on their comparative performance in a test of cure context
      is lacking. This study aims to address this gap. METHODS: We compared the
      technical and clinical performance of Abbott RealTime High risk (HR)-HPV,
      Genprobe Aptima PV, Hologic Cervista HPV-HR, Qiagen Hybrid Capture 2 and Roche
      cobas HPV in the Early Implementation phase of a 'test of cure' service within
      the Scottish Cervical Screening Programme. RESULTS: Valid results with all five
      HPV Tests from 1020 first samples taken ~6 months post-treatment showed HPV
      positivity ranging from 17.84% to 26.96%. There was perfect agreement in 74%, and
      greatest variation between assays was observed in cytologically negative samples.
      Clinical performance was judged on cumulative incidence of cervical
      intraepithelial neoplasia 2+ (CIN2+) during follow-up (mean: 13.2 months). There
      were 23 cases of CIN2+ of which 14 were CIN3+. All assays, including cytology,
      were 100% sensitive for detection of CIN3+. Of the nine cases of residual CIN2,
      three assays detected all, one assay missed one and one assay missed two cases.
      Specificity ranged from 75% to 84% according to assay. CONCLUSIONS: All assays
      were sensitive for detection of CIN2+ at 6 months post-treatment. The range of
      positivity equated to a 50% increase between assays with the lowest and highest
      positivity rates. The relevance of HPV positivity in the absence of cytological
      abnormalities requires longer follow-up to determine whether additional tools for
      risk stratification are required.

PMID- 24436338
TI  - Internal hydraulic redistribution prevents the loss of root conductivity during
      drought.
AB  - Shrubs of the Great Basin desert in Utah are subjected to a prolonged summer
      drought with the potential consequence of reduced water transport capability of
      the xylem due to drought-induced cavitation. Hydraulic redistribution (HR) is the
      passive movement of water from deep to shallow soil through plant roots.
      Hydraulic redistribution can increase water availability in shallow soil and
      ameliorate drought stress, providing better soil and root water status, which
      could affect shallow root conductivity (Ks) and native root embolism. We tested
      this hypothesis in an Artemisia tridentata Nutt. mono-specific stand grown in a
      common garden in Utah. We enhanced HR artificially by applying a once a week deep
      irrigation treatment increasing the water potential gradient between deep and
      shallow soil layers. Plants that were deep-watered had less negative water
      potentials and greater stomatal conductance and transpiration rates than non
      watered control plants. After irrigation with labeled water (deltaD), xylem water
      in stems and shallow roots of watered shrubs was enriched with respect to control
      shrubs, a clear indication of deep water uptake and HR. Shallow root conductivity
      was threefold greater and shrubs experienced lower native embolism when deep
      watered. We found clear evidence of water transfer between deep and shallow roots
      through internal HR that delayed depletion of shallow soil water content,
      maintained Ks and prevented root embolism. Overall, our results show a positive
      effect of HR on root water transport capacity in otherwise dry soil, with
      important implications for plant water status. 

PMID- 24436339
TI  - Are dietary interventions effective at increasing fruit and vegetable consumption
      among overweight children? A systematic review.
AB  - INTRODUCTION: Childhood obesity is now a global epidemic and the incidence
      continues to increase. Dietary interventions and nutritional education are
      possible options to manage childhood obesity. However, restrictive diets can
      result in negative outcomes, and therefore it may be more apt to encourage
      children to consume more fruit and vegetables and thereby develop a healthier
      positive attitude towards food. METHOD: A systematic review of literature of
      interventions to increase fruit and/or vegetable consumption in overweight or
      obese children and adolescents was conducted, applying a free-text strategy with
      a set of search terms. RESULTS: A total of five studies describing seven
      interventions published in international peer-reviewed journals and meeting the
      review's eligibility criteria were identified. All five studies examined family
      focused interventions to increase daily fruit and vegetable consumption measured
      either by child self-report or parent report. Only one intervention reported a
      lasting statistically significant increased consumption of fruit and vegetables.
      CONCLUSIONS: This review highlights that in order to tackle obesity narrow
      interventions focusing on single aspects of behaviour are unlikely to achieve
      long-term change. Successful public health interventions tackling childhood
      obesity will need to take a holistic approach and target behaviour change in
      multiple aspects of children's lifestyles and their surroundings, including
      nutritional education, parental support and physical activity.

PMID- 24436340
TI  - Novel PAX9 mutations cause non-syndromic tooth agenesis.
AB  - PAX9 is a transcription factor expressed in the tooth mesenchyme during tooth
      morphogenesis. In Pax9-null mice, tooth development is arrested at the bud stage.
      In humans, heterozygous mutations in PAX9 have been associated with non-syndromic
      tooth agenesis, predominantly in the molars. Here, we report 2 novel mutations in
      the paired domain of PAX9, a three-nucleotide deletion (73-75 delATC) and a
      missense mutation (C146T), in two unrelated Japanese patients with non-syndromic
      tooth agenesis. The individual with the 73-75del ATC mutation was missing all
      maxillary molars and mandibular second and third molars. The individual with the
      C146T mutation was missing the mandibular central incisors, maxillary second
      premolars, and first molars, along with all second and third molars. Both
      mutations affected amino acids that are highly conserved among different species
      and are critical for DNA binding. When both mutants were transfected to COS7
      cells, nuclear localization of PAX9 proteins was not affected. However, reduced
      expression of the mutant proteins and almost no transcriptional activity of the
      target BMP4 gene were observed, suggesting haploinsufficiency of PAX9 as the
      cause of non-syndromic tooth agenesis. 

PMID- 24436341
TI  - The use of unprescribed antibiotics in management of upper respiratory tract
      infection in children in Enugu, South East Nigeria.
AB  - BACKGROUND: It is a documented fact that upper respiratory tract infection (URTI)
      is more of a viral illness. OBJECTIVES: This study aims at documenting the
      prevalence of the use of unprescribed antibiotics in children aged <5 years with
      upper respiratory symptomatology. METHODS: Four hundred twenty-three mother-child
      pairs were enrolled for this study. Chi-square and logistic regression analysis
      were used to find association between use of unprescribed antibiotics and
      variables of interest. RESULTS: The prevalence of unprescribed antibiotics in
      children aged <5 years in the management of URTI is 75.9%. The antibiotics abuse
      was commoner in older children with URTI (45.9% in children aged 12-24 months)
      and among mothers with higher educational attainment. CONCLUSION: Antibiotics
      abuse among mothers is high. Government, through its responsible agencies, should
      enforce stricter control or outrightly stop sale of antibiotics over-the-counter
      to prevent the dreaded antibiotics resistance.

PMID- 24436342
TI  - Editorial transition.

PMID- 24436343
TI  - Human neuroimaging and the BRAIN initiative: a joint statement from the ASNR and
      ASFNR, with the support of the RSNA, ACR, ARR, and ISMRM.

PMID- 24436344
TI  - Comment on "Reproducibility of cerebrospinal venous blood flow and vessel anatomy
      with the use of phase contrast-vastly undersampled isotropic projection
      reconstruction and contrast-enhanced MRA".

PMID- 24436345
TI  - Will a randomized trial of unruptured brain arteriovenous malformations change
      our clinical practice?

PMID- 24436346
TI  - Stenotic transverse sinus predisposes to poststenting hyperperfusion syndrome as
      evidenced by quantitative analysis of peritherapeutic cerebral circulation time.
AB  - BACKGROUND AND PURPOSE: Hyperperfusion syndrome is a devastating complication of
      carotid stent placement. The shortening of cerebral circulation time after stent
      placement is seen as a good indicator of the development of hyperperfusion
      syndrome. The purpose of our study was to evaluate whether patients with
      ipsilateral transverse sinus stenosis are prone to having shortened cerebral
      circulation time after stent placement, subsequently leading to the possible
      development of hyperperfusion syndrome. MATERIALS AND METHODS: Forty-nine
      patients with >70% unilateral carotid stenosis undergoing stent placement were
      recruited for analysis. Group A consisted of patients with a stenotic ipsilateral
      transverse sinus >50% greater than the diameter of the contralateral transverse
      sinus; the remaining patients were in group B. Quantitative DSA was used to
      calculate cerebral circulation time. Cerebral circulation time was defined as the
      time difference between the relative time to maximal intensity of ROIs in the
      proximal internal carotid artery and the internal jugular vein. DeltaCCT was
      defined as cerebral circulation time before stent placement minus cerebral
      circulation time after stent placement. DeltaCCT, white matter hyperintensity
      signals, and sulcal effacement in MR imaging were compared between the 2 groups.
      RESULTS: DeltaCCT was significantly shorter in group A (0.65 +/- 1.3) than in
      group B (-0.12 +/- 1.4). Three patients had white matter hyperintensity signals
      in group A, and 1 developed hyperperfusion syndrome. Group B showed no MR imaging
      signs of hyperperfusion syndrome. CONCLUSIONS: Ipsilateral hypoplastic transverse
      sinus was associated with prolonged cerebral circulation time before stent
      placement and greatly shortened cerebral circulation time after stent placement.
      Inadequate venous drainage might play a role in impaired cerebral autoregulation
      and might influence the development of poststenting hyperperfusion syndrome.

PMID- 24436347
TI  - Prenatal diagnosis of fetal ventriculomegaly: Agreement between fetal brain
      ultrasonography and MR imaging.
AB  - BACKGROUND AND PURPOSE: Accurate measurement of the lateral ventricles is of
      paramount importance in prenatal diagnosis. Possible conflicting classifications
      caused by their measurement in different sectional planes by sonography and MR
      imaging are frequently raised. The objective of our study was to evaluate the
      agreement between ultrasonography and MR imaging in the measurement of the
      lateral ventricle diameter in the customary sectional planes for each technique.
      MATERIALS AND METHODS: Measurement of both lateral ventricles was performed
      prospectively in 162 fetuses from 21 to 40 weeks of gestational age referred for
      evaluation due to increased risk for cerebral pathology. The mean gestational age
      for evaluation was 32 weeks. The measurements were performed in the customary
      plane for each technique: axial plane for sonography and coronal plane for MR
      imaging. RESULTS: The 2 techniques yielded results in substantial agreement by
      using intraclass correlation and kappa coefficient score tests. When we assessed
      the clinical cutoff of 10 mm, the kappa score was 0.94 for the narrower ventricle
      and 0.84 for the wider ventricle, expressing almost perfect agreement. The Bland
      Altman plot did not show any trend regarding the actual width of the ventricle,
      gestational week, or interval between tests. Findings were independent for fetal
      position, sex, and indication for examination. CONCLUSIONS: Our study indicates
      excellent agreement between fetal brain ultrasonography and MR imaging as to the
      diagnosis of fetal ventriculomegaly in the customarily used sectional planes of
      each technique.

PMID- 24436348
TI  - Association of white matter hyperintensities with low serum 25-hydroxyvitamin D
      levels.
AB  - BACKGROUND AND PURPOSE: Vitamin D deficiency is associated with cognitive
      impairment in the elderly and with increased white matter T2 hyperintensities in
      elderly debilitated patients. We investigated the relationship between serum
      vitamin D and brain MR findings in adult outpatients. MATERIALS AND METHODS:
      Brain MR studies of 56 patients ages 30-69 years were selected when vitamin D
      level had been obtained within 90 days of the MRI. White matter T2
      hyperintensities were characterized by size and location by two
      neuroradiologists. Manual volumetric analysis was assessed in patients more than
      50 years of age. RESULTS: The entire cohort showed a significant negative
      relationship between serum 25-hydroxyvitamin D and the number of confluent
      juxtacortical white matter T2 hyperintensities (P = .047). The cohort ages 50
      years and older showed stronger correlation between confluent white matter T2
      hyperintensities and serum 25-hydroxyvitamin D in the juxtacortical region;
      number (P = .015) and size of white matter T2 hyperintensities (P = .048).
      Atrophy was not significantly related to serum 25-hydroxyvitamin D by radiologist
      visual analysis or by the bicaudate ratio. CONCLUSIONS: We found a significant
      relationship between vitamin D and white matter T2 hyperintensities in
      independent adult outpatients, especially over the age of 50 years.

PMID- 24436349
TI  - Efficacy of early Mycoplasma hyopneumoniae vaccination against mixed respiratory
      disease in older fattening pigs.
AB  - The present field study investigated the efficacy of early Mycoplasma
      hyopneumoniae vaccination in a farrow-to-finish pig herd with respiratory disease
      late in the fattening period due to combined infections with M hyopneumoniae and
      viral pathogens. Five hundred and forty piglets were randomly divided into three
      groups of 180 piglets each: two groups were vaccinated (Stellamune Once) at
      either 7 (V1) or 21 days of age (V2), and a third group was left non-vaccinated
      (NV). The three treatment groups were housed in different pens within the same
      compartment during the nursery period, and were housed in different but identical
      compartments during the fattening period. The efficacy was evaluated using
      performance and pneumonia lesions. The average daily weight gain during the
      fattening period was 19 (V1) and 18 g/day (V2) higher in both vaccinated groups
      when compared with the NV group. However, the difference was not statistically
      significant (P>0.05). The prevalence of pneumonia was significantly lower in both
      vaccinated groups (V1: 71.5 and V2: 67.1 per cent) when compared with the NV
      group (80.2 per cent) (P<0.05). There were no significant differences between the
      two vaccination groups. In conclusion, in the present herd with respiratory
      disease during the second half of the fattening period caused by M hyopneumoniae
      and viral infections, prevalence of pneumonia lesions were significantly reduced
      and growth losses numerically (not statistically significant) decreased by both
      vaccination schedules. 

PMID- 24436350
TI  - Hormonal and neuromuscular responses to high-level middle- and long-distance
      competition.
AB  - PURPOSE: The purpose of this study was to analyze the effects of high-level
      competition on salivary free cortisol, countermovement jump (CMJ), and rating of
      perceived exertion (RPE) and the relationships between these fatigue indicators
      in a group of elite middle- and long-distance runners. METHOD: The salivary free
      cortisol levels and CMJ height of 10 high-level middle- and long-distance runners
      (7 men, 3 women; age 27.6 +/- 5.1y) competing in 800-m, 1500-m, 3000-m, or 5000-m
      events in the 2013 Spanish National Championships were measured throughout a 4-wk
      baseline period, then again before and after their respective races on the day of
      the competition. Athletes' RPE was also measured after their races. RESULTS:
      Cortisol increased significantly after the race compared with the value measured
      90 min before the race (+98.3%, g = 0.82, P < .05), while CMJ height decreased
      significantly after the race (-3.9%, g = 0.34, P < .05). The decrease in CMJ
      height after the race correlates significantly with the postcompetition cortisol
      increase (r = .782, P < .05) and the RPE assessment (r = .762, P < .01).
      CONCLUSIONS: Observed differences in CMJ height correlate significantly with
      salivary free cortisol levels and RPE of middle- and long-distance runners. These
      results show the suitability of the CMJ for monitoring multifactorial competition
      responses in high-level middle- and long-distance runners.

PMID- 24436351
TI  - Variability of measurements of sweat sodium using the regional absorbent-patch
      method.
AB  - CONTEXT: There is interest in including recommendations for the replacement of
      the sodium lost in sweat in individualized hydration plans for athletes. PURPOSE:
      Although the regional absorbent-patch method provides a practical approach to
      measuring sweat sodium losses in field conditions, there is a need to understand
      the variability of estimates associated with this technique. METHODS: Sweat
      samples were collected from the forearms, chest, scapula, and thigh of 12
      cyclists during 2 standardized cycling time trials in the heat and 2 in temperate
      conditions. Single measure analysis of sodium concentration was conducted
      immediately by ion-selective electrodes (ISE). A subset of 30 samples was frozen
      for reanalysis of sodium concentration using ISE, flame photometry (FP), and
      conductivity (SC). RESULTS: Sweat samples collected in hot conditions produced
      higher sweat sodium concentrations than those from the temperate environment (P =
      .0032). A significant difference (P = .0048) in estimates of sweat sodium
      concentration was evident when calculated from the forearm average (mean +/- 95%
      CL; 64 +/- 12 mmol/L) compared with using a 4-site equation (70 +/- 12 mmol/L).
      There was a high correlation between the values produced using different
      analytical techniques (r2 = .95), but mean values were different between
      treatments (frozen FP, frozen SC > immediate ISE > frozen ISE; P < .0001).
      CONCLUSION: Whole-body sweat sodium concentration estimates differed depending on
      the number of sites included in the calculation. Environmental testing conditions
      should be considered in the interpretation of results. The impact of sample
      freezing and subsequent analytical technique was small but statistically
      significant. Nevertheless, when undertaken using a standardized protocol, the
      regional absorbent-patch method appears to be a relatively robust field test.

PMID- 24436353
TI  - Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic
      fatty liver disease induced by a high-fat and high-carbohydrate diet in mice.
AB  - Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and
      diet. It is associated with insulin resistance (IR) in hepatic and peripheral
      tissues. Here, we aimed to characterize the severity of diet-induced steatosis,
      obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and
      DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high
      carbohydrate (HFHC) or control diet for 16 wk followed by the application of a
      combination of classic physiological, biochemical, and pathological studies to
      determine obesity and hepatic steatosis. Peripheral IR was characterized by
      measuring blood glucose level, serum insulin level, homeostasis model assessment
      of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in
      adipose tissues, whereas the level of hepatic IR was determined by measuring
      insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J
      and DBA/2J mice developed obesity to a similar degree without the feature of
      liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the
      HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in
      hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice
      in the HFHC diet group developed only a mild degree of pericentrilobular hepatic
      steatosis that was associated with moderate changes in peripheral IR.
      Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC
      diet treatment. Collectively, these data suggest that the severity of diet
      induced hepatic steatosis is correlated to the level of peripheral IR, not with
      the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a
      dominant factor of pathophysiology in nonalcoholic fatty liver disease. 

PMID- 24436354
TI  - No improvement of repeated-sprint performance with dietary nitrate.
AB  - PURPOSE: Nitrate supplementation improves endurance exercise and single bouts of
      high-intensity activity, but its effect on repeated sprints is unclear. This
      study is the first to investigate the effects of acute dietary nitrate
      supplementation during a high-intensity intermittent-sprint test to exhaustion.
      METHODS: Team-sport athletes (9 male, age 22.3 +/- 2.1 y, VO2max 57.4 +/- 8.5 mL
      . kg-1 . min-1; 7 female, age 20.7 +/- 1.3 y, VO2max 47.2 +/- 8.5 mL . kg-1 . min
      1) were assigned to a double-blind, randomized, crossover design. Participants
      consumed 70 mL of concentrated beetroot juice containing a minimum of 0.3 g of
      nitrate (NT) or 70 mL of placebo (PL) 2 h before a repeated-sprint protocol
      involving repeated 8-s sprints with 30-s recovery on a cycle ergometer to
      exhaustion. RESULTS: Fewer sprints (NT = 13 +/- 5 vs PL = 15 +/- 6, P = .005, d =
      0.41) and less total work (NT = 49.2 +/- 24.2 kJ vs PL = 57.8 +/- 34.0 kJ, P =
      .027, d = 0.3) were completed in NT relative to PL. However there was no
      difference in overall mean power output or the mean power output for each
      individual 8-s sprint. CONCLUSIONS: These findings suggest that dietary nitrate
      is not beneficial for improving repeated-sprint performance, at least when such
      sprints are near-maximal and frequent in nature. The lack of an effect of nitrate
      at near-maximal oxygen uptake supports the suggestion that at greater exercise
      intensities nitrate does not have an ergogenic effect.

PMID- 24436352
TI  - Role of GATA factors in development, differentiation, and homeostasis of the
      small intestinal epithelium.
AB  - The small intestinal epithelium develops from embryonic endoderm into a highly
      specialized layer of cells perfectly suited for the digestion and absorption of
      nutrients. The development, differentiation, and regeneration of the small
      intestinal epithelium require complex gene regulatory networks involving multiple
      context-specific transcription factors. The evolutionarily conserved GATA family
      of transcription factors, well known for its role in hematopoiesis, is essential
      for the development of endoderm during embryogenesis and the renewal of the
      differentiated epithelium in the mature gut. We review the role of GATA factors
      in the evolution and development of endoderm and summarize our current
      understanding of the function of GATA factors in the mature small intestine. We
      offer perspective on the application of epigenetics approaches to define the
      mechanisms underlying context-specific GATA gene regulation during intestinal
      development. 

PMID- 24436355
TI  - Validity of the Yo-Yo Intermittent Recovery Test Level 1 for direct measurement
      or indirect estimation of maximal oxygen uptake in female soccer players.
AB  - PURPOSE: To evaluate the validity of the Yo-Yo Intermittent Recovery Test Level 1
      (YYIR1) for the direct assessment and the indirect estimation of maximal oxygen
      consumption (VO2max) in female soccer players compared with a maximal laboratory
      treadmill test (LTT). METHODS: Eighteen female soccer players (21.5 +/- 3.4 y,
      165.6 +/- 7.5 cm, 63.3 +/- 7.4 kg; mean +/- SD) completed an LTT and a YYIR1 in
      random order (1 wk apart). Their VO2max was directly measured via portable
      spirometry during both tests and indirectly estimated from a published non-gender
      specific formula (YYIR1-F1). RESULTS: The measured VO2max values in LTT and YYIR1
      were 55.0 +/- 5.3 and 49.9 +/- 4.9 mL . kg-1 . min-1, respectively, while the
      estimated VO2max values from YYIR1-F1 corresponded to 45.2 +/- 3.4 mL . kg-1 .
      min-1. Large positive correlations between the VO2max values from YYIR1 and LTT
      (r = .83, P < .001, 90% confidence interval = .64-.92) and YYIR1-F1 and LTT (r =
      .67, P = .002, .37-.84) were found. However, the YYIR1 significantly
      underestimated players' VO2max by 9.4% compared with LTT (P < .001) with Bland
      Altman 95% limits of agreement ranging from -20.0% to 1.4%. A significant
      underestimation from the YYIR1-F1 (P < .001) was also identified (17.8% with
      Bland-Altman 95% limits of agreement ranging from -31.8% to -3.8%). CONCLUSIONS:
      The YYIR1 and YYIR1-F1 are not accurate methods for the direct assessment or
      indirect estimation of VO2max in female soccer players. The YYIR1-F1 lacks gender
      specificity, which might have been the reason for its larger error.

PMID- 24436356
TI  - Surgical simulation flexor tendon repair using Thiel cadavers: a comparison with
      formalin embalmed cadavers and porcine models.
AB  - The aim of this study was to compare Thiel-embalmed cadavers with formalin
      embalmed cadavers and porcine models in the surgical simulation repair of a Zone
      II flexor tendon division. Nine participants were recruited to the study. The
      models were assessed using a five-point scale. Assessment was divided into tissue
      quality, surgical approach and identification of structures. Thiel cadavers rated
      consistently higher compared with the formalin and porcine models (mean 37 SD 2,
      22 SD 6 and 23 SD 5, respectively). Thiel cadavers recorded an average tendon
      glide of 21 mm SD 5, formalin cadavers 2 mm SD 2 and the porcine model 6 mm SD 2.
      We have demonstrated the benefit of Thiel embalming, with flexibility of tissues
      allowing testing of the repair of a flexor tendon in a realistic anatomical
      model. LEVEL OF EVIDENCE: Level V.

PMID- 24436357
TI  - Use of the DePuySynthes(r) Ulna Osteotomy System for large ulnar shortenings.

PMID- 24436358
TI  - Median nerve neuropathy associated with cubital heterotopic ossification.

PMID- 24436359
TI  - Single-stage reconstruction of flexor tendons with vascularized tendon transfers.
AB  - The reconstruction of finger flexor tendons with vascularized flexor digitorum
      superficialis (FDS) tendon grafts (flaps) based on the ulnar vessels as a single
      stage is not a popular technique. We reviewed 40 flexor tendon reconstructions
      (four flexor pollicis longus and 36 finger flexors) with vascularized FDS tendon
      grafts in 38 consecutive patients. The donor tendons were transferred based on
      the ulnar vessels as a single-stage procedure (37 pedicled flaps, three free
      flaps). Four patients required composite tendon and skin island transfer. Minimum
      follow-up was 12 months, and functional results were evaluated using a total
      active range of motion score. Multiple linear regression analysis was performed
      to evaluate the factors that could be associated with the postoperative total
      active range of motion. The average postoperative total active range of motion
      (excluding the thumbs) was 178.05 degrees  (SD 50 degrees ). The total active
      range of motion was significantly lower for patients who were reconstructed with
      free flaps and for those who required composite tendon and skin island flap. Age,
      right or left hand, donor/motor tendon and pulley reconstruction had no linear
      effect on total active range of motion. Overall results were comparable with a
      published series on staged tendon grafting but with a lower complication rate.
      Vascularized pedicled tendon grafts/flaps are useful in the reconstruction of
      defects of finger flexor tendons in a single stage, although its role in the
      reconstructive armamentarium remains to be clearly established. 

PMID- 24436360
TI  - Percutaneous fixation of transverse shaft fractures of the proximal phalanx with
      a new compression wire.

PMID- 24436361
TI  - Metacarpophalangeal and interphalangeal joint arthrodesis: a comparative study
      between tension band and compression screw fixation.
AB  - A retrospective, comparative cohort study was performed of metacarpophalangeal or
      proximal interphalangeal joint arthrodesis with either tension band (n = 28) or
      compression (Acutrak Mini) screw (n = 29) methods. We compared rate of union,
      healing time, complications, and re-operation rate. Union was achieved in 26/28
      (92.8%) of the tension band group (9.4 weeks) and 24/28 (85.7%) of the
      compression screw group (9.8 weeks). Only 28 patients in the screw group were
      assessed for union as one patient in the screw group sustained a fracture at the
      time of insertion and was converted to tension band fixation. The complication
      rate was 8/28 (28.6%) in the tension band group and 8/29 (27.6%) in the
      compression screw group. Re-operation rate was 9/28 (32.1%) in the tension band
      group and 1/29 (3.6%) in the compression screw group. Our findings indicate that
      bone healing, healing time, and complications are similar in both groups. The
      tension band technique had a significantly higher re-operation rate (hardware
      removal), but was the technique for salvage following failure of the screw
      technique. 

PMID- 24436362
TI  - The 2014 Surgeon General's report: commemorating the 50th Anniversary of the 1964
      Report of the Advisory Committee to the US Surgeon General and updating the
      evidence on the health consequences of cigarette smoking.
AB  - The question of whether cigarette smoking was associated with lung cancer was
      central to the expansion of epidemiology into the study of chronic diseases in
      the 1950s. The culmination of this era was the 1964 report of the Advisory
      Committee to the Surgeon General, a landmark document that included an objective
      synthesis of the evidence of the health consequences of smoking according to
      causal criteria. The report concluded that cigarette smoking was a cause of lung
      cancer in men and sufficient in scope that "remedial action" was warranted at the
      societal level. The 2014 Surgeon General's report commemorates the 50th
      anniversary of the 1964 report. The evidence on the health consequences of
      smoking has been updated many times in Surgeon General's reports since 1964.
      These have summarized our increasingly greater understanding of the broad
      spectrum of the deleterious health effects of exposure to tobacco smoke across
      most major organ systems. In turn, this evidence has been translated into tobacco
      control strategies implemented to protect the public's health. The Surgeon
      General report process is an enduring example of evidence-based public health in
      practice. Substantial progress has been made, but cigarette smoking remains one
      of the most pressing global health issues of our time. 

PMID- 24436365
TI  - Cholestasis and meconium ileus in infants with cystic fibrosis and their clinical
      outcomes.
AB  - OBJECTIVE: To identify the incidence and outcomes of cholestasis and meconium
      ileus (MI) in infants with cystic fibrosis (CF). DESIGN: Retrospective cohort
      study. SETTING: Single-centre study. PATIENTS: From January 1986 to December
      2011, 401 infants with CF (69 with MI) presented to our centre. MAIN OUTCOME
      MEASUREMENTS: (1) incidence of cholestasis, (2) identification of risk factors
      for cholestasis, (3) association between the presence of cholestasis and MI and
      the development of clinically significant CF-associated liver disease (CFLD)
      defined as multilobular cirrhosis with portal hypertension. RESULTS: Cholestasis
      occurred in 23 of 401 infants (5.7%). There was a significantly higher incidence
      of cholestasis in infants with MI (27.1%) compared to those without MI (1.2%)
      (p<0.001). Infants with MI had a 30.36-fold increased risk of developing
      cholestasis compared to those without MI (p<0.001). Cholestasis resolved in all
      children, at a median (range) age of 9.2 (0.8-53.2) months in the MI group and
      10.2 (2.0-19.4) months in the non-MI group. The majority of cholestatic infants
      (87.0%) and infants with MI (92.8%) did not develop clinically significant CFLD,
      not significantly different than either the 93.9% of non-cholestatic infants nor
      the 93.7% infants without MI. CONCLUSIONS: Cholestasis is an uncommon condition
      in CF affecting only 5.7% of the screened newborn CF population. The greatest
      risk factor for developing cholestasis is the presence of MI. However, the
      presence of MI appears not to be associated with the development of CFLD. An
      effect of neonatal cholestasis on the development of CFLD cannot be excluded by
      this study.

PMID- 24436366
TI  - Guidelines to identify abnormalities after childhood urinary tract infections: a
      prospective audit.
AB  - OBJECTIVE: To compare the childhood urinary tract infection (UTI) guidelines from
      the Royal College of Physicians (RCP) in 1991 and from National Institute of
      Health and Care Excellence (NICE) (CG54) in 2007 by measuring their efficiency at
      detecting urinary tract abnormalities. DESIGN: Children with UTIs within the
      Newcastle Primary Care Trust (population 70,800 children) were referred and
      imaged according to the RCP guidelines during 2008, and these were compared to
      the activity that would have been undertaken if we had implemented the CG54
      guidelines, including following them through 2011 to identify those with
      recurrent UTIs. MAIN OUTCOME MEASURES: The numbers of children imaged, the
      imaging burden and efficiency, and urinary tract abnormalities detected by each
      guideline. RESULTS: Fewer children would have been imaged by CG54 than RCP (150
      vs 427), but its sensitivity was lower, at 44% for detecting scarring, 10% for
      identifying vesicoureteric reflux and 40% for other abnormalities. Overall, it
      would have only detected one-quarter of the abnormal cases (8 vs 32) and would
      have missed five of nine children with scarring, including three with multiple
      lesions and one with renal impairment. Imposing an age restriction of <8 years to
      the RCP guidelines would reduce its screening rate by 20% and still detect 90% of
      the abnormalities. INTERPRETATION: The CG54 guidelines do not alter the imaging
      efficiency compared to the RCP guidelines, but they are considerably less
      sensitive.

PMID- 24436367
TI  - Antiangiogenic therapy inhibits venous thrombus resolution.
AB  - OBJECTIVE: Venous thromboembolism is a common complication in patients with
      cancer, resulting in significant morbidity and mortality. Clinical studies
      suggest that the incidence of venous thromboembolic events increased after
      treatment of these patients with antiangiogenic agents. Thrombi resolve through a
      process of remodeling, involving the formation of microvascular channels within
      the thrombus. Our aim was to determine whether inhibiting angiogenesis affects
      venous thrombus resolution. APPROACH AND RESULTS: Thrombus was induced in the
      inferior vena cava of mice. These mice were treated with axitinib (50 mg/kg per
      day), 2-methoxyestradiol (2ME, 150 mg/kg per day), or vehicle control. Thrombus
      size, recanalization, neovascularization, inflammatory cell content, and collagen
      content were assessed after axitinib (days 3, 10, 17) and 2ME (day 10 only)
      treatment (n=6/group). Axitinib treatment resulted in reduced thrombus resolution
      (P<0.002) and vein recanalization (P<0.001) compared with vehicle-treated
      controls. This was associated with inhibition of organization as seen through
      reduced thrombus neovascularization (P<0.0001) and collagen (P<0.0001) content,
      as well as reduced macrophage accumulation in the thrombus (P<0.001). Treatment
      with a second antiangiogenic agent, 2ME, mirrored these findings, with a similar
      order of magnitude of effect of treatment over vehicle control in all of the
      parameters measured, with the exception of neutrophil content, which was
      significantly reduced after 2ME treatment but not affected by axitinib.
      CONCLUSIONS: Antiangiogenic therapy (using axitinib and 2ME) inhibits the
      resolution of venous thrombi, which could lead to persistent venous obstruction
      and the possibility of thrombus extension. This potential prolongation of venous
      occlusion by antiangiogenic agents should therefore be taken into consideration
      in trials of these agents and when managing the complications of venous
      thromboembolic events in patients with cancer.

PMID- 24436368
TI  - Chemokines in atherosclerosis: proceedings resumed.
AB  - Chemokines play important roles in atherosclerotic vascular disease. Expressed by
      not only cells of the vessel wall but also emigrated leukocytes, chemokines were
      initially discovered to direct leukocytes to sites of inflammation. However,
      chemokines can also exert multiple functions beyond cell recruitment. Here, we
      discuss novel and recently emerging aspects of chemokines and their involvement
      in atherosclerosis. While reviewing newly identified roles of chemokines and
      their receptors in monocyte and neutrophil recruitment during atherogenesis and
      atheroregression, we also revisit homeostatic functions of chemokines, including
      their roles in cell homeostasis and foam cell formation. The functional diversity
      of chemokines in atherosclerosis warrants a clear-cut mechanistic dissection and
      stage-specific assessment to better appreciate the full scope of their actions in
      vascular inflammation and to identify pathways that harbor the potential for a
      therapeutic targeting of chemokines in atherosclerosis. 

PMID- 24436369
TI  - Functional analysis of two haplotypes of the human endothelial protein C receptor
      gene.
AB  - OBJECTIVE: To confirm the effect of the endothelial protein receptor gene (PROCR)
      haplotypes H1 and H3 on venous thromboembolism (VTE), to study their effect on
      endothelial protein C receptor (EPCR) expression in human umbilical vein
      endothelial cells, and to investigate the functionality of H1 tagging single
      nucleotide polymorphisms in an in vitro model. APPROACH AND RESULTS: Protein C
      (PC), activated PC, and soluble EPCR (sEPCR) levels were measured in 702 patients
      with VTE and 518 healthy individuals. All subjects were genotyped for PROCR H1
      and H3. Human umbilical vein endothelial cells isolated from 111 umbilical cords
      were used to study the relation between PROCR haplotypes, PROCR mRNA, cellular
      distribution of EPCR, and rate of PC activation. Finally, the functionality of
      the intragenic PROCR H1 single-nucleotide polymorphisms was analyzed using a
      luciferase-based method. We confirmed that individuals carrying H1 have reduced
      VTE risk, increased plasma activated PC levels, and reduced plasma sEPCR levels
      and that individuals with the H3H3 genotype have an increased VTE risk and
      increased plasma sEPCR levels. In cultured human umbilical vein endothelial
      cells, H1 is associated with increased membrane-bound EPCR, increased rate of PC
      activation, and reduced sEPCR in conditioned medium, but does not significantly
      influence PROCR mRNA levels. In contrast, H3 is associated with reduced membrane
      bound EPCR and increased sEPCR in human umbilical vein endothelial cell
      conditioned medium, higher levels of a truncated mRNA isoform, and a lower rate
      of PC activation. Finally, we identified the g.2132T>C single-nucleotide
      polymorphism in intron 1 as an intragenic H1-specific functional single
      nucleotide polymorphism. CONCLUSIONS: These results support a protective role of
      PROCR H1 against VTE and an increased risk of VTE associated with the H3
      haplotype.

PMID- 24436371
TI  - Subclinical atherosclerosis in systemic lupus erythematosus and antiphospholipid
      syndrome: focus on beta2GPI-specific T cell response.
AB  - OBJECTIVE: Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS)
      are associated with a high prevalence of atherosclerosis. beta2 glycoprotein I
      (beta2GPI) represents a link between autoimmunity and endothelial dysfunction.
      Recently, beta2GPI reactive T cells have been identified; however, their role in
      atherosclerosis is still under investigation. We evaluated early atherosclerosis
      in patients with SLE and APS and investigated T cell reactivity to beta2GPI and
      its relationship with atherosclerotic process. APPROACH AND RESULTS: Fifty SLE,
      18 patients with primary APS (PAPS), and 25 healthy controls were enrolled.
      Demographic and clinical data, including traditional cardiovascular risk factors,
      were recorded. Monocyte beta2GPI and Tissue Factor (TF) expression and peripheral
      blood mononuclear cell response to beta2GPI stimulation were evaluated. Doppler
      ultrasound was performed to investigate flow-mediated dilatation (FMD) and
      carotid intima-media thickness (IMT). We detected an increase in mean IMT and a
      decrease in FMD in patients with SLE versus controls (P<0.05 and P=0.0001,
      respectively) and a decrease in FMD in patients with PAPS versus controls
      (P<0.05). Monocyte beta2GPI and TF expression was higher in patients with SLE and
      PAPS than in controls (P=0.006 and P=0.001, respectively); no correlation of
      monocyte beta2GPI and TF with IMT or FMD was detected. beta2GPI induced
      peripheral blood mononuclear cell proliferation in 32% of patients with SLE, 25%
      of patients with PAPS yet in none of the controls. Proliferative response to
      beta2GPI correlated with a history of arterial thrombosis, thrombocytopenia, and
      IMT >0.9 mm. CONCLUSIONS: A significant percentage of patients with SLE and PAPS
      show a beta2GPI-specific T cell reactivity, which is associated with subclinical
      atherosclerosis.

PMID- 24436370
TI  - Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by
      limiting translation control-dependent retardation of inflammation.
AB  - OBJECTIVE: Unresolved inflammatory response of macrophages plays a pivotal role
      in the pathogenesis of atherosclerosis. Previously we showed that ribosomal
      protein L13a-dependent translational silencing suppresses the synthesis of a
      cohort of inflammatory proteins in monocytes and macrophages. We also found that
      genetic abrogation of L13a expression in macrophages significantly compromised
      the resolution of inflammation in a mouse model of lipopolysaccharide-induced
      endotoxemia. However, its function in the pathogenesis of atherosclerosis is not
      known. Here, we examine whether L13a in macrophage has a protective role against
      high-fat diet-induced atherosclerosis. APPROACH AND RESULTS: We bred the
      macrophage-specific L13a knockout mice L13a Flox(+/+) Cre(+/+) onto
      apolipoprotein E-deficient background and generated the experimental double
      knockout mice L13a Flox(+/+) Cre(+/+) apolipoprotein E deficient (apoE(-/-)).
      L13a Flox(+/+) Cre(-/-) mice on apolipoprotein E-deficient background were used
      as controls. Control and knockout mice were subjected to high-fat diet for 10
      weeks. Evaluation of aortic sinus sections and entire aorta by en face showed
      significantly higher atherosclerosis in the knockout mice. Severity of
      atherosclerosis in knockout mice was accompanied by thinning of the smooth muscle
      cell layer in the media, larger macrophage area in the intimal plaque region and
      higher plasma levels of inflammatory cytokines. In addition, macrophages isolated
      from knockout mice had higher polyribosomal abundance of several target mRNAs,
      thus showing defect in translation control. CONCLUSIONS: Our data demonstrate
      that loss of L13a in macrophages increases susceptibility to atherosclerosis in
      apolipoprotein E-deficient mice, revealing an important role of L13a-dependent
      translational control as an endogenous protection mechanism against
      atherosclerosis.

PMID- 24436372
TI  - Protective role for Toll-like receptor-9 in the development of atherosclerosis in
      apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Atherosclerosis is driven by inflammatory reactions that are shared
      with the innate immune system. Toll-like receptor-9 (TLR9) is an intracellular
      pattern recognition receptor of the innate immune system that is currently under
      clinical investigation as a therapeutic target in inflammatory diseases. Here, we
      investigated whether TLR9 has a role in the development of atherosclerosis in
      apolipoprotein E-deficient (ApoE(-/-)) mice. APPROACH AND RESULTS: Newly
      generated double-knockout ApoE(-/-):TLR9(-/-) mice and control ApoE(-/-) mice
      were fed a high-fat diet from 8 weeks and effects on lesion size, cellular
      composition, inflammatory status, and plasma lipids were assessed after 8, 12,
      15, and 20 weeks. All 4 time points demonstrated exacerbated atherosclerotic
      lesion severity in ApoE(-/-):TLR9(-/-) mice, with a corresponding increase in
      lipid deposition and accumulation of macrophages, dendritic cells, and CD4(+) T
      cells. Although ApoE(-/-):TLR9(-/-) mice exhibited an increase in plasma very low
      density lipoprotein/low-density-lipoprotein cholesterol, the very low-density
      lipoprotein/low-density lipoprotein:high-density lipoprotein ratio was unaltered
      because of a parallel increase in plasma high-density lipoprotein cholesterol. As
      a potential mechanism accounting for plaque progression in ApoE(-/-):TLR9(-/-)
      mice, CD4(+) T-cell accumulation was further investigated and depletion of these
      cells in ApoE(-/-):TLR9(-/-) mice significantly reduced lesion severity. As a
      final translational approach, administration of a TLR9 agonist (type B CpG
      oligodeoxynucleotide 1668) to ApoE(-/-) mice resulted in a reduction of lesion
      severity. CONCLUSIONS: Genetic deletion of the innate immune receptor TLR9
      exacerbated atherosclerosis in ApoE(-/-) mice fed a high-fat diet. CD4(+) T cells
      were identified as potential mediators of this effect. A type B CpG
      oligodeoxynucleotide TLR9 agonist reduced lesion severity, thus identifying a
      novel therapeutic approach in atherosclerosis.

PMID- 24436373
TI  - Periodic heartbeat reversals cause cardiogenic inspiration and expiration with
      coupled spiracle leakage in resting blowflies, Calliphora vicina.
AB  - Respiration in insects is thought to be independent of the circulatory system
      because insects typically lack respiratory pigments and because oxygen transport
      occurs in the gaseous phase through a ramified tracheal system by diffusion and
      convection directly to the tissues. In the blowfly, as in other insects with
      periodic heartbeat reversal, the haemolymph is periodically shifted between the
      anterior body and abdomen, exerting alternating pressure changes on the compliant
      tracheae in the thorax and in the abdomen. Simultaneous pressure and O2 optode
      measurements show that, during negative pressure periods, the tracheal partial
      pressure of oxygen (PO2) increases by 0.5 kPa. In the quiescent fly, tracheal PO2
      is rather high (17.5-18.9 kPa), although the thoracic spiracles remain
      constricted. Microscopic video recordings and reflectance measurements revealed
      that the dorsal soft edges of the valve lips of the second spiracle leave a very
      small leak, which is passively widened during backward pulses of the heart. Thus,
      negative pressure, combined with increased leakage of the spiracle Sp2 valve
      enable inspiration in the thorax. The positive pressure periods are correlated
      with a new type of convective CO2 micro-bursts as shown in flow-through
      measurements. The bulk of the CO2 is, however, released after longer interbursts
      in macro-bursts with actively opening valves reminiscent of the open phase in a
      cyclic gas exchange. When the valves open, the PO2 in the thoracic air sacs
      unexpectedly drops by a mean of 2.75+/-1.09 kPa, suggesting a displacement of O2
      by the transient accumulation of CO2 in the tracheal system before its release.

PMID- 24436374
TI  - Structured variability of steady-speed locomotion in rats.
AB  - By examining key locomotor parameters during terrestrial locomotion on a
      substrate without irregularities, we show that rats frequently accelerate and
      decelerate between two consecutive steps while maintaining an overall steady
      speed and that the touchdown order of contralateral limbs significantly
      influences those speed adjustments. The latter highly correlates with significant
      adjustments in relative forelimb protraction at touchdown and hindlimb extension
      at lift-off. We conclude that this remarkable level of variability in limb
      coordination would clearly be advantageous for the functional flexibility needed
      during terrestrial locomotion on much more irregular (rough) natural terrain. In
      addition, its occurrence on a substrate lacking irregularities suggests that much
      of stable, terrestrial steady-speed locomotion in rats is mechanically
      controlled. 

PMID- 24436375
TI  - The evolution of micro-cursoriality in mammals.
AB  - In this study we report on the evolution of micro-cursoriality, a unique case of
      cursoriality in mammals smaller than 1 kg. We obtained new running speed and limb
      morphology data for two species of elephant-shrews (Elephantulus spp.,
      Macroscelidae) from Namaqualand, South Africa, which we compared with published
      data for other mammals. Elephantulus maximum running speeds were higher than
      those of most mammals smaller than 1 kg. Elephantulus also possess exceptionally
      high metatarsal:femur ratios (1.07) that are typically associated with fast
      unguligrade cursors. Cursoriality evolved in the Artiodactyla, Perissodactyla and
      Carnivora coincident with global cooling and the replacement of forests with open
      landscapes in the Oligocene and Miocene. The majority of mammal species, though,
      remained non-cursorial, plantigrade and small (<1 kg). The extraordinary running
      speed and digitigrady of elephant-shrews was established in the Early Eocene in
      the earliest macroscelid Prodiacodon, but was probably inherited from Paleocene,
      Holarctic stem macroscelids. Micro-cursoriality in macroscelids evolved from the
      plesiomorphic plantigrade foot of the possum-like ancestral mammal earlier than
      in other mammalian crown groups. Micro-cursoriality evolved first in forests,
      presumably in response to selection for rapid running speeds facilitated by local
      knowledge, in order to avoid predators. During the Miocene, micro-cursoriality
      was pre-adaptive to open, arid habitats, and became more derived in the newly
      evolved Elephantulus and Macroscelides elephant-shrews with trail running. 

PMID- 24436376
TI  - Regulation of the Rana sylvatica brevinin-1SY antimicrobial peptide during
      development and in dorsal and ventral skin in response to freezing, anoxia and
      dehydration.
AB  - Brevinin-1SY is the only described antimicrobial peptide (AMP) of Rana sylvatica.
      As AMPs are important innate immune molecules that inhibit microbes, this study
      examined brevinin-1SY regulation during development and in adult frogs in
      response to environmental stress. The brevinin-1SY nucleotide sequence was
      identified and used for protein modeling. Brevinin-1SY was predicted to be an
      amphipathic, hydrophobic, alpha helical peptide that inserts into a lipid
      bilayer. Brevinin-1SY transcripts were detected in tadpoles and were
      significantly increased during the later stages of development. Effects of
      environmental stress (24 h anoxia, 40% dehydration or 24 h frozen) on the mRNA
      levels of brevinin-1SY in the dorsal and ventral skin were examined. The brevinin
      1SY mRNA levels were increased in dorsal and ventral skin of dehydrated frogs,
      and in ventral skin of anoxic frogs, compared with controls (non-stressed).
      Brevinin-1SY protein levels in peptide extracts of dorsal skin showed a similar,
      but not significant, trend to that of brevinin-1SY mRNA levels. Antimicrobial
      activity of skin extracts from control and stressed animals were assessed for
      Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Botrytis cinerea,
      Rhizopus stolonifer and Pythium sulcatum using disk diffusion assays. Peptide
      extracts of dorsal skin from anoxic, frozen and dehydrated animals showed
      significantly higher inhibition of E. coli and P. sulcatum than from control
      animals. In ventral skin peptide extracts, significant growth inhibition was
      observed in frozen animals for E. coli and P. sulcatum, and in anoxic animals for
      B. cinerea, compared with controls. Environmental regulation of brevinin-1SY may
      have important implications for defense against pathogens. 

PMID- 24436377
TI  - Stress inhibition of melatonin synthesis in the pineal organ of rainbow trout
      (Oncorhynchus mykiss) is mediated by cortisol.
AB  - Cortisol has been suggested to mediate the effect of stress on pineal melatonin
      synthesis in fish. Therefore, we aimed to determine how pineal melatonin
      synthesis is affected by exposing rainbow trout to different stressors, such as
      hypoxia, chasing and high stocking density. In addition, to test the hypothesis
      that cortisol is a mediator of such stress-induced effects, a set of animals were
      intraperitoneally implanted with coconut oil alone or containing cortisol (50 mg
      kg(-1) body mass) and sampled 5 or 48 h post-injection at midday and midnight.
      The specificity of such effect was also assessed in cultured pineal organs
      exposed to cortisol alone or with the general glucocorticoid receptor antagonist,
      mifepristone (RU486). Stress (in particular chasing and high stocking density)
      affected the patterns of plasma and pineal organ melatonin content during both
      day and night, with the greatest reduction occurring at night. The decrease in
      nocturnal melatonin levels in the pineal organ of stressed fish was accompanied
      by increased serotonin content and decreased AANAT2 enzymatic activity and mRNA
      abundance. Similar effects on pineal melatonin synthesis to those elicited by
      stress were observed in trout implanted with cortisol for either 5 or 48 h. These
      data indicate that stress negatively influences the synthesis of melatonin in the
      pineal organ, thus attenuating the day-night variations of circulating melatonin.
      The effect might be mediated by increased cortisol, which binds to trout pineal
      organ-specific glucocorticoid receptors to modulate melatonin rhythms. Our
      results in cultured pineal organs support this. Considering the role of melatonin
      in the synchronization of daily and annual rhythms, the results suggest that
      stress-induced alterations in melatonin synthesis could affect the availability
      of fish to integrate rhythmic environmental information. 

PMID- 24436379
TI  - Honeybee drones are attracted by groups of consexuals in a walking simulator.
AB  - During the mating season, honeybee males, the drones, gather in congregation
      areas 10-40 m above ground. When a receptive female, a queen, enters the
      congregation, drones are attracted to her by queen-produced pheromones and visual
      cues and attempt to mate with the queen in mid-air. It is still unclear how
      drones and queens find the congregations. Visual cues on the horizon are most
      probably used for long-range orientation. For shorter-range orientation, however,
      attraction by a drone-produced aggregation pheromone has been proposed, yet so
      far its existence has not been confirmed conclusively. The low accessibility of
      congregation areas high up in the air is a major hurdle and precise control of
      experimental conditions often remains unsatisfactory in field studies. Here, we
      used a locomotion compensator-based walking simulator to investigate drones'
      innate odor preferences under controlled laboratory conditions. We tested
      behavioral responses of drones to 9-oxo-2-decenoic acid (9-ODA), the major queen
      produced sexual attractant, and to queen mandibular pheromone (QMP), an
      artificial blend of 9-ODA and several other queen-derived components. While 9-ODA
      strongly dominates the odor bouquet of virgin queens, QMP rather resembles the
      bouquet of mated queens. In our assay, drones were attracted by 9-ODA, but not by
      QMP. We also investigated the potential attractiveness of male-derived odors by
      testing drones' orientation responses to the odor bouquet of groups of 10 living
      drones or workers. Our results demonstrate that honeybee drones are attracted by
      groups of other drones (but not by workers), which may indicate a role of drone
      emitted cues for the formation of congregations. 

PMID- 24436378
TI  - Activation of the cnidarian oxidative stress response by ultraviolet radiation,
      polycyclic aromatic hydrocarbons and crude oil.
AB  - Organisms are continuously exposed to reactive chemicals capable of causing
      oxidative stress and cellular damage. Antioxidant enzymes, such as superoxide
      dismutases (SODs) and catalases, are present in both prokaryotes and eukaryotes
      and provide an important means of neutralizing such oxidants. Studies in
      cnidarians have previously documented the occurrence of antioxidant enzymes
      (transcript expression, protein expression and/or enzymatic activity), but most
      of these studies have not been conducted in species with sequenced genomes or
      included phylogenetic analyses, making it difficult to compare results across
      species due to uncertainties in the relationships between genes. Through searches
      of the genome of the sea anemone Nematostella vectensis Stephenson, one catalase
      gene and six SOD family members were identified, including three copper/zinc
      containing SODs (CuZnSODs), two manganese-containing SODs (MnSODs) and one copper
      chaperone of SOD (CCS). In 24 h acute toxicity tests, juvenile N. vectensis
      showed enhanced sensitivity to combinations of ultraviolet radiation (UV) and
      polycyclic aromatic hydrocarbons (PAHs, specifically pyrene, benzo[a]pyrene and
      fluoranthene) relative to either stressor alone. Adult N. vectensis exhibited
      little or no mortality following UV, benzo[a]pyrene or crude oil exposure but
      exhibited changes in gene expression. Antioxidant enzyme transcripts were both
      upregulated and downregulated following UV and/or chemical exposure. Expression
      patterns were most strongly affected by UV exposure but varied between
      experiments, suggesting that responses vary according to the intensity and
      duration of exposure. These experiments provide a basis for comparison with other
      cnidarian taxa and for further studies of the oxidative stress response in N.
      vectensis.

PMID- 24436380
TI  - Measuring individual locomotor rhythms in honey bees, paper wasps and other
      similar-sized insects.
AB  - Circadian rhythms in social insects are highly plastic and are modulated by
      multiple factors. In addition, complex behaviors such as sun-compass orientation
      and time learning are clearly regulated by the circadian system in these
      organisms. Despite these unique features of social insect clocks, the mechanisms
      as well as the functional and evolutionary relevance of these traits remain
      largely unknown. Here we show a modification of the Drosophila activity
      monitoring (DAM) system that allowed us to measure locomotor rhythms of the honey
      bee, Apis mellifera (three variants; gAHB, carnica and caucasica), and two paper
      wasps (Polistes crinitus and Mischocyttarus phthisicus). A side-by-side
      comparison of the endogenous period under constant darkness (free-running period)
      led us to the realization that these social insects exhibit significant
      deviations from the Earth's 24 h rotational period as well as a large degree of
      inter-individual variation compared with Drosophila. Experiments at different
      temperatures, using honey bees as a model, revealed that testing the endogenous
      rhythm at 35 degrees C, which is the hive's core temperature, results in average
      periods closer to 24 h compared with 25 degrees C (23.8 h at 35 degrees C versus
      22.7 h at 25 degrees C). This finding suggests that the degree of tuning of
      circadian temperature compensation varies among different organisms. We expect
      that the commercial availability, cost-effectiveness and integrated nature of
      this monitoring system will facilitate the growth of the circadian field in these
      social insects and catalyze our understanding of the mechanisms as well as the
      functional and evolutionary relevance of circadian rhythms. 

PMID- 24436382
TI  - Physiological correlates of symbiont migration during bleaching of two octocoral
      species.
AB  - Perturbed colonies of Phenganax parrini and Sarcothelia sp. exhibit migration of
      symbionts of Symbiodinium spp. into the stolons. Densitometry and visual
      inspection indicated that polyps bleached while stolons did not. When migration
      was triggered by temperature, light and confinement, colonies of Sarcothelia sp.
      decreased rates of oxygen formation in the light (due to the effects of
      perturbation on photosynthesis and respiration) and increased rates of oxygen
      uptake in the dark (due to the effects of perturbation on respiration alone).
      Colonies of P. parrini, by contrast, showed no significant changes in either
      aspect of oxygen metabolism. When migration was triggered by light and
      confinement, colonies of Sarcothelia sp. showed decreased rates of oxygen
      formation in the light and increased rates of oxygen uptake in the dark, while
      colonies of P. parrini maintained the former and increased the latter. During
      symbiont migration into their stolons, colonies of both species showed dramatic
      increases in reactive oxygen species (ROS), as visualized with a fluorescent
      probe, with stolons of Sarcothelia sp. exhibiting a nearly immediate increase of
      ROS. Differences in symbiont type may explain the greater sensitivity of colonies
      of Sarcothelia sp. Using fluorescent probes, direct measurements of migrating
      symbionts in the stolons of Sarcothelia sp. showed higher levels of reactive
      nitrogen species and lower levels of ROS than the surrounding host tissue. As
      measured by native fluorescence, levels of NAD(P)H in the stolons were unaffected
      by perturbation. Symbiont migration thus correlates with dramatic physiological
      changes and may serve as a marker for coral condition.

PMID- 24436381
TI  - Brains over brawn: experience overcomes a size disadvantage in fish social
      hierarchies.
AB  - Life experiences can alter cognitive abilities and subsequent behavior. Here we
      asked whether differences in experience could affect social status. In
      hierarchical animal societies, high-ranking males that typically win aggressive
      encounters gain territories and hence access to mates. To understand the relative
      contributions of social experience and physical environment on status, we used a
      highly territorial African cichlid fish species, Astatotilapia burtoni, that
      lives in a dynamic lek-like social hierarchy. Astatotilapia burtoni males are
      either dominant or submissive and can switch status rapidly depending on the
      local environment. Although dominant males are innately aggressive, we wondered
      whether they modulated their aggression based on experience. We hypothesized that
      as males mature they might hone their fighting tactics based on observation of
      other males fighting. We compared males of different ages and sizes in distinctly
      different physical environments and subsequently tested their fighting skills. We
      found that a size difference previously thought negligible (<10% body length)
      gave a significant advantage to the larger opponent. In contrast, we found no
      evidence that increasing environmental complexity affected status outcomes.
      Surprisingly, we found that males only a few days older than their opponents had
      a significant advantage during territorial disputes so that being older
      compensated for the disadvantage of being smaller. Moreover, the slightly older
      winners exploited a consistent fighting strategy, starting with lower levels of
      aggression on the first day that significantly increased on the second day, a
      pattern absent in younger winners. These data suggest that experience is an
      advantage during fights for status, and that social learning provides more
      relevant experience than the physical complexity of the territory.

PMID- 24436383
TI  - Genetic and phenotypically flexible components of seasonal variation in immune
      function.
AB  - Animals cope with seasonal variation in environmental factors by adjustments of
      physiology and life history. When seasonal variation is partly predictable, such
      adjustments can be based on a genetic component or be phenotypically flexible.
      Animals have to allocate limited resources over different demands, including
      immune function. Accordingly, immune traits could change seasonally, and such
      changes could have a genetic component that differs between environments. We
      tested this hypothesis in genotypically distinct groups of a widespread songbird,
      the stonechat (Saxicola torquata). We compared variation in immunity during 1
      year in long-distance migrants, short-distance migrants, tropical residents and
      hybrids in a common garden environment. Additionally, we investigated
      phenotypically flexible responses to temperature by applying different
      temperature regimes to one group. We assessed constitutive immunity by measuring
      hemagglutination, hemolysis, haptoglobin and bactericidal ability against
      Escherichia coli and Staphylococcus aureus. Genotypic groups differed in patterns
      of variation of all measured immune indices except haptoglobin. Hybrids differed
      from, but were rarely intermediate to, parental subspecies. Temperature treatment
      only influenced patterns of hemolysis and bactericidal ability against E. coli.
      We conclude that seasonal variation in constitutive immunity has a genetic
      component, that heredity does not follow simple Mendelian rules, and that some
      immune measures are relatively rigid while others are more flexible. Furthermore,
      our results support the idea that seasonal variability in constitutive immunity
      is associated with variability in environment and annual-cycle demands. This
      study stresses the importance of considering seasonal variation in immune
      function in relation to the ecology and life history of the organism of interest.

PMID- 24436384
TI  - Differential effects of vitamins E and C and carotenoids on growth, resistance to
      oxidative stress, fledging success and plumage colouration in wild great tits.
AB  - Oxidative stress is the imbalance between the production of reactive species and
      antioxidants, which causes damage to lipids, proteins and DNA. Antioxidants, like
      vitamins and carotenoids, can limit oxidative damage and can therefore regulate
      the trade-off between growth, which is a period of high reactive species
      production, and self-maintenance. However, the role of carotenoids as
      antioxidants in vivo has been debated, and it has been suggested that carotenoid
      based signals indicate the availability of non-pigmentary antioxidants (e.g.
      vitamins) that protect carotenoids from oxidation, known as the 'protection
      hypothesis'. To evaluate the importance of vitamins versus carotenoids as
      antioxidants during growth and to test the protection hypothesis, we supplemented
      nestling great tits, Parus major, 3, 5 and 7 days after hatching with a single
      dose of carotenoids and/or vitamins in a 2*2 full-factorial design. We
      subsequently measured body condition, antioxidant capacity, oxidative damage,
      fledging success and plumage reflectance. Vitamins enhanced antioxidant capacity,
      but did not affect oxidative damage. Vitamin-treated nestlings had higher growth
      rates and higher probability of fledging. In contrast, carotenoids did not affect
      any of these traits. Furthermore, carotenoid-based colouration increased over the
      breeding season in nestlings that received vitamins only. This study shows that
      vitamins are limiting for growth rate and fledging success, and suggests that
      vitamins could regulate the trade-off between growth and self-maintenance in
      favour of the former. Moreover, our results are consistent with the idea that
      carotenoids are minor antioxidants in birds, but they do not support the
      protection hypothesis.

PMID- 24436385
TI  - Neurohormonal changes associated with ritualized combat and the formation of a
      reproductive hierarchy in the ant Harpegnathos saltator.
AB  - Dominance rank in animal societies is correlated with changes in both
      reproductive physiology and behavior. In some social insects, dominance status is
      used to determine a reproductive division of labor, where a few colony members
      reproduce while most remain functionally sterile. Changes in reproduction and
      behavior in this context must be coordinated through crosstalk between the brain
      and the reproductive system. We investigated a role for biogenic amines in
      forming this connection in the ant Harpegnathos saltator. In this species,
      workers engage in an elaborate dominance tournament to establish a group of
      reproductive workers termed gamergates. We analyzed biogenic amine content in the
      brains of gamergates, inside-workers and foragers under stable colony conditions
      and found that gamergates had the highest levels of dopamine. Dopamine levels
      were also positively correlated with increased ovarian activity among gamergates.
      Next, we experimentally induced workers to compete in a reproductive tournament
      to determine how dopamine may be involved in the establishment of a new
      hierarchy. Dopamine levels rose in aggressive workers at the start of a
      tournament, while workers that were policed by their nestmates (a behavior that
      inhibits ovarian activity) showed a rapid decline in dopamine. In addition to
      dopamine, levels of serotonin and tyramine differed among castes, and these
      changes could contribute to differences in caste-specific behavioral patterns
      observed among non-reproductive workers. Overall, these results provide support
      that biogenic amines link changes in behavior and dominance with reproductive
      activity in H. saltator as well as drive differences in worker task performance.

PMID- 24436386
TI  - High basal metabolic rate does not elevate oxidative stress during reproduction
      in laboratory mice.
AB  - Increased oxidative stress (OS) has been suggested as a physiological cost of
      reproduction. However, previous studies reported ambiguous results, with some
      even showing a reduction of oxidative damage during reproduction. We tested
      whether the link between reproduction and OS is mediated by basal metabolic rate
      (BMR), which has been hypothesized to affect both the rate of radical oxygen
      species production and antioxidative capacity. We studied the effect of
      reproduction on OS in females of laboratory mice divergently selected for high (H
      BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental
      investment. Non-reproducing L-BMR females showed higher oxidative damage to
      lipids (quantified as the level of malondialdehyde in internal organ tissues) and
      DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females.
      Reproduction did not affect oxidative damage to lipids in either line; however,
      it reduced damage to DNA in L-BMR females. Reproduction increased catalase
      activity in liver (significantly stronger in L-BMR females) and decreased it in
      kidneys. We conclude that the effect of reproduction on OS depends on the initial
      variation in BMR and varies between studied internal organs and markers of OS.

PMID- 24436387
TI  - Simultaneous high-resolution pH and spectrophotometric recordings of oxygen
      binding in blood microvolumes.
AB  - Oxygen equilibrium curves have been widely used to understand oxygen transport in
      numerous organisms. A major challenge has been to monitor oxygen binding
      characteristics and concomitant pH changes as they occur in vivo, in limited
      sample volumes. Here we report a technique allowing highly resolved and
      simultaneous monitoring of pH and blood pigment saturation in minute blood
      volumes. We equipped a gas diffusion chamber with a broad-range fibre-optic
      spectrophotometer and a micro-pH optode and recorded changes of pigment
      oxygenation along oxygen partial pressure (PO2) and pH gradients to test the
      setup. Oxygen binding parameters derived from measurements in only 15 MUl of
      haemolymph from the cephalopod Octopus vulgaris showed low instrumental error
      (0.93%) and good agreement with published data. Broad-range spectra, each
      resolving 2048 data points, provided detailed insight into the complex absorbance
      characteristics of diverse blood types. After consideration of photobleaching and
      intrinsic fluorescence, pH optodes yielded accurate recordings and resolved a
      sigmoidal shift of 0.03 pH units in response to changing PO2 from 0 to 21 kPa.
      Highly resolved continuous recordings along pH gradients conformed to stepwise
      measurements at low rates of pH changes. In this study we showed that a diffusion
      chamber upgraded with a broad-range spectrophotometer and an optical pH sensor
      accurately characterizes oxygen binding with minimal sample consumption and
      manipulation. We conclude that the modified diffusion chamber is highly suitable
      for experimental biologists who demand high flexibility, detailed insight into
      oxygen binding as well as experimental and biological accuracy combined in a
      single setup.

PMID- 24436388
TI  - Measuring gill paracellular permeability with polyethylene glycol-4000 in freely
      swimming trout: proof of principle.
AB  - The influence of swimming activity on gill paracellular permeability has not been
      measured previously in fishes. We critically assessed the use of tritium-labeled
      polyethylene glycol ([(3)H]PEG-4000) for this purpose, a substance that is also a
      classic marker for extracellular fluid volume, glomerular filtration rate and
      drinking rate. Tests (8 h) on resting freshwater trout showed that when measuring
      [(3)H]PEG-4000 clearance from the plasma in the efflux direction, correction for
      a large excretion via glomerular filtration was essential, necessitating urinary
      catheterization. When measuring [(3)H]PEG-4000 clearance from the water in the
      influx direction, correction for a significant uptake by drinking was essential,
      necessitating terminal gut removal, whereas glomerular filtration losses were
      minimal. After correction for these alternate routes of loss and uptake,
      [(3)H]PEG-4000 clearance rates by efflux from the plasma and by influx from the
      water were identical, showing that gill paracellular permeability is not
      rectified, and can be measured in either direction. The influx technique with
      terminal gut removal was used to assess gill paracellular permeability in trout
      without urinary catheters freely swimming at 1.2 body lengths s(-1) for 8 h.
      Branchial [(3)H]PEG-4000 clearance rate (by influx from the water) increased
      significantly by ~80% in accord with a similar measured increase in O2
      consumption rate. Thus in trout, gill paracellular permeability does increase
      during exercise, in accord with the traditional concept of the osmorespiratory
      compromise.

PMID- 24436389
TI  - Cross-generation plasticity in cold hardiness is associated with diapause, but
      not the non-diapause developmental pathway, in the blow fly Calliphora vicina.
AB  - Predicting insect responses to global climate change involves understanding cross
      generation effects of temperature. The majority of temperate insects overwinter
      in a state of diapause, a pre-emptive response to winter conditions associated
      with increased cold hardiness. Diapause is often induced following maternal adult
      detection of an environmental cue signifying the onset of winter, whilst diapause
      is initiated in a subsequent life stage and/or generation. Continued global
      warming will expose adults to higher late-autumn temperatures, whilst diapause
      life stages will still experience prolonged winter cold. The cross-generation
      effect of temperature was investigated by acclimating adult Calliphora vicina to
      present-day (15 degrees C) and future (20 degrees C) late-autumn conditions and
      assessing cold-hardiness in diapause (D15 and D20) and non-diapause (ND15 and
      ND20) progeny. A cross-generation plasticity in cold hardiness was associated
      with D but not ND larvae. D15 larvae exhibited an enhanced ability to suppress
      internal freezing (supercooling point=-18.9+/-0.9 degrees C) compared with D20 (
      15.3+/-0.8 degrees C), and displayed a greater tolerance of prolonged exposure to
      -4 degrees C (LT50=26.0+/-1.0 and 11.4+/-1.1 days, respectively) and -8 degrees C
      (5.1+/-1.1 and 3.0+/-1.1 days, respectively). These changes were associated with
      a reduced glucose content in D15 (2.4+/-0.3 g mg(-1)) compared with D20 (3.0+/
      0.3 g mg(-1)) larvae. In conclusion, C. vicina adults exposed to warmer autumn
      conditions during diapause induction will produce larvae with a reduced cold
      hardiness capacity, which could negatively impact winter survival. Given that
      maternal regulation of diapause is common among temperate insects, this could be
      a widespread phenomenon.

PMID- 24436390
TI  - Heart rate as a predictor of metabolic rate in heterothermic bats.
AB  - While heart rate (fH) has been used as an indicator of energy expenditure,
      quantitative data showing the relationship between these variables are only
      available for normothermic animals. To determine whether fH also predicts oxygen
      consumption ( ) during torpor, we simultaneously measured , fH and subcutaneous
      body temperature (Tsub) of a hibernator, Gould's long-eared bats (Nyctophilus
      gouldi, 9 g, N=18), at ambient temperatures (Ta) between 0 and 25 degrees C. At
      rest, fH of normothermic resting bats was negatively correlated with Ta, with
      maximum fH of 803 beats min(-1) (Ta=5 degrees C). During torpor, the relationship
      between fH and Ta was curvilinear, and at low Tsub (~6 degrees C), fH fell to a
      minimum average of 8 beats min(-1). The minimum average values for both and fH in
      torpor reported here were among the lowest recorded for bats. The relationship
      between fH and was significant for both resting (r(2)=0.64, P<0.001) and torpid
      bats (r(2)=0.84, P<0.001), with no overlap between the two states. These
      variables were also significantly correlated (r(2)=0.44, P<0.001) for entire
      torpor bouts. Moreover, estimates of from fH did not differ significantly from
      measured values during the different physiological states. Our study is the first
      to investigate the accuracy of fH as a predictor of during torpor and indicates
      the reliability of this method as a potential measure of energy expenditure in
      the field. Nevertheless, fH should only be used to predict within the range of
      activities for which robust correlations have been established.

PMID- 24436391
TI  - Reproducibility.

PMID- 24436396
TI  - Infectious diseases. Guinea worm eradication at risk in South Sudanese war.

PMID- 24436397
TI  - U.S. spending. Final 2014 budget helps science agencies rebound.

PMID- 24436398
TI  - Air pollution. Ammonia pollution from farming may exact hefty health costs.

PMID- 24436399
TI  - Ecology. Parasitic puppeteers begin to yield their secrets.

PMID- 24436400
TI  - Astronomy. Star-crossing planets literally strut their stuff.

PMID- 24436401
TI  - Gut instinct.

PMID- 24436402
TI  - The second act.

PMID- 24436403
TI  - Biodiversity: broaden the search.

PMID- 24436404
TI  - Biodiversity: Ecuador deters protection efforts.

PMID- 24436405
TI  - Targeting deforestation.

PMID- 24436406
TI  - Urban forests on the front line.

PMID- 24436407
TI  - Urban forests on the front line--response.

PMID- 24436408
TI  - Evolution. Smells like queen since the Cretaceous.

PMID- 24436410
TI  - Chemistry.A clear path for polymer crystallization.

PMID- 24436409
TI  - Medicine. How thalidomide works against cancer.

PMID- 24436411
TI  - Biochemistry. Many paths to the origin of life.

PMID- 24436412
TI  - Molecular biology. Ribose--an internal threat to DNA.

PMID- 24436413
TI  - Retrospective. Frederick Sanger (1918-2013).

PMID- 24436414
TI  - Single-crystal linear polymers through visible light-triggered topochemical
      quantitative polymerization.
AB  - One of the challenges in polymer science has been to prepare large-polymer single
      crystals. We demonstrate a visible light-triggered quantitative topochemical
      polymerization reaction based on a conjugated dye molecule. Macroscopic-size,
      high-quality polymer single crystals are obtained. Polymerization is not limited
      to single crystals, but can also be achieved in highly concentrated solution or
      semicrystalline thin films. In addition, we show that the polymer decomposes to
      monomer upon thermolysis, which indicates that the polymerization
      depolymerization process is reversible. The physical properties of the polymer
      crystals enable us to isolate single-polymer strands via mechanical exfoliation,
      which makes it possible to study individual, long polymer chains. 

PMID- 24436415
TI  - Nonenzymatic sugar production from biomass using biomass-derived gamma
      valerolactone.
AB  - Widespread production of biomass-derived fuels and chemicals will require cost
      effective processes for breaking down cellulose and hemicellulose into their
      constituent sugars. Here, we report laboratory-scale production of soluble
      carbohydrates from corn stover, hardwood, and softwood at high yields (70 to 90%)
      in a solvent mixture of biomass-derived gamma-valerolactone (GVL), water, and
      dilute acid (0.05 weight percent H2SO4). GVL promotes thermocatalytic
      saccharification through complete solubilization of the biomass, including the
      lignin fraction. The carbohydrates can be recovered and concentrated (up to 127
      grams per liter) by extraction from GVL into an aqueous phase by addition of NaCl
      or liquid CO2. This strategy is well suited for catalytic upgrading to furans or
      fermentative upgrading to ethanol at high titers and near theoretical yield. We
      estimate through preliminary techno-economic modeling that the overall process
      could be cost-competitive for ethanol production, with biomass pretreatment
      followed by enzymatic hydrolysis. 

PMID- 24436416
TI  - Atomic-scale variability and control of III-V nanowire growth kinetics.
AB  - In the growth of nanoscale device structures, the ultimate goal is atomic-level
      precision. By growing III-V nanowires in a transmission electron microscope, we
      measured the local kinetics in situ as each atomic plane was added at the
      catalyst-nanowire growth interface by the vapor-liquid-solid process. During
      growth of gallium phosphide nanowires at typical V/III ratios, we found
      surprising fluctuations in growth rate, even under steady growth conditions. We
      correlated these fluctuations with the formation of twin defects in the nanowire,
      and found that these variations can be suppressed by switching to growth
      conditions with a low V/III ratio. We derive a growth model showing that this
      unexpected variation in local growth kinetics reflects the very different supply
      pathways of the V and III species. The model explains under which conditions the
      growth rate can be controlled precisely at the atomic level. 

PMID- 24436417
TI  - Conserved class of queen pheromones stops social insect workers from reproducing.
AB  - A major evolutionary transition to eusociality with reproductive division of
      labor between queens and workers has arisen independently at least 10 times in
      the ants, bees, and wasps. Pheromones produced by queens are thought to play a
      key role in regulating this complex social system, but their evolutionary history
      remains unknown. Here, we identify the first sterility-inducing queen pheromones
      in a wasp, bumblebee, and desert ant and synthesize existing data on compounds
      that characterize female fecundity in 64 species of social insects. Our results
      show that queen pheromones are strikingly conserved across at least three
      independent origins of eusociality, with wasps, ants, and some bees all appearing
      to use nonvolatile, saturated hydrocarbons to advertise fecundity and/or suppress
      worker reproduction. These results suggest that queen pheromones evolved from
      conserved signals of solitary ancestors. 

PMID- 24436418
TI  - Identification of a plant receptor for extracellular ATP.
AB  - Extracellular adenosine 5'-triphosphate (ATP) is an essential signaling molecule
      that is perceived in mammals by plasma membrane P2-type purinoceptors. Similar
      ATP receptors do not exist in plants, although extracellular ATP has been shown
      to play critical roles in plant growth, development, and stress responses. Here,
      we identify an ATP-insensitive Arabidopsis mutant, dorn1 (Does not Respond to
      Nucleotides 1), defective in lectin receptor kinase I.9 (Arabidopsis Information
      Resource accession code At5g60300). DORN1 binds ATP with high affinity
      (dissociation constant of 45.7 +/- 3.1 nanomolar) and is required for ATP-induced
      calcium response, mitogen-activated protein kinase activation, and gene
      expression. Ectopic expression of DORN1 increased the plant response to physical
      wounding. We propose that DORN1 is essential for perception of extracellular ATP
      and likely plays a variety of roles in plant stress resistance. 

PMID- 24436419
TI  - Btk29A promotes Wnt4 signaling in the niche to terminate germ cell proliferation
      in Drosophila.
AB  - Btk29A is the Drosophila ortholog of the mammalian Bruton's tyrosine kinase
      (Btk), mutations of which in humans cause a heritable immunodeficiency disease.
      Btk29A mutations stabilized the proliferating cystoblast fate, leading to an
      ovarian tumor. This phenotype was rescued by overexpression of wild-type Btk29A
      and phenocopied by the interference of Wnt4-beta-catenin signaling or its
      putative downstream nuclear protein Piwi in somatic escort cells. Btk29A and
      mammalian Btk directly phosphorylated tyrosine residues of beta-catenin, leading
      to the up-regulation of its transcriptional activity. Thus, we identify a
      transcriptional switch involving the kinase Btk29A/Btk and its phosphorylation
      target, beta-catenin, which functions downstream of Wnt4 in escort cells to
      terminate Drosophila germ cell proliferation through up-regulation of piwi
      expression. This signaling mechanism likely represents a versatile developmental
      switch. 

PMID- 24436420
TI  - Changes in rRNA transcription influence proliferation and cell fate within a stem
      cell lineage.
AB  - Ribosome biogenesis drives cell growth and proliferation, but mechanisms that
      modulate this process within specific lineages remain poorly understood. Here, we
      identify a Drosophila RNA polymerase I (Pol I) regulatory complex composed of
      Under-developed (Udd), TAF1B, and a TAF1C-like factor. Disruption of udd or TAF1B
      results in reduced ovarian germline stem cell (GSC) proliferation. Female GSCs
      display high levels of ribosomal RNA (rRNA) transcription, and Udd becomes
      enriched in GSCs relative to their differentiating daughters. Increasing Pol I
      transcription delays differentiation, whereas reducing rRNA production induces
      both morphological changes that accompany multicellular cyst formation and
      specific decreased expression of the bone morphogenetic protein (BMP) pathway
      component Mad. These findings demonstrate that modulating rRNA synthesis fosters
      changes in the cell fate, growth, and proliferation of female Drosophila GSCs and
      their daughters. 

PMID- 24436421
TI  - Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous
      cell carcinomas.
AB  - Mining modern genomics for cancer therapies is predicated on weeding out
      "bystander" alterations (nonconsequential mutations) and identifying "driver"
      mutations responsible for tumorigenesis and/or metastasis. We used a direct in
      vivo RNA interference (RNAi) strategy to screen for genes that upon repression
      predispose mice to squamous cell carcinomas (SCCs). Seven of our top hits
      including Myh9, which encodes nonmuscle myosin IIa-have not been linked to tumor
      development, yet tissue-specific Myh9 RNAi and Myh9 knockout trigger invasive SCC
      formation on tumor-susceptible backgrounds. In human and mouse keratinocytes,
      myosin IIa's function is manifested not only in conventional actin-related
      processes but also in regulating posttranscriptional p53 stabilization. Myosin
      IIa is diminished in human SCCs with poor survival, which suggests that in vivo
      RNAi technology might be useful for identifying potent but low-penetrance tumor
      suppressors. 

PMID- 24436423
TI  - Contribution of extramedullary organs in myocardial inflammation and remodeling:
      does the spleen cause cardiac melancholy?

PMID- 24436424
TI  - Impact of early evidence of atherosclerotic changes on early treatment in
      children with familial hypercholesterolemia.

PMID- 24436425
TI  - Proliferating macrophages populate established atherosclerotic lesions.

PMID- 24436426
TI  - Jeffery Molkentin: delves into cell death. Interview by Ruth Williams.

PMID- 24436427
TI  - Role of exosomes in myocardial remodeling.
AB  - Exosomes are nanovesicles released from cells through exocytosis and are known to
      be mediators of proximal as well as distant cell-to-cell signaling. They are
      surrounded by a classical bilayered membrane with an exceptionally high
      cholesterol/phospholipid ratio. Exosomes were first described in 1977, then named
      prostasomes, and in 1987 the name exosome was coined. Exosomes contain surface
      proteins, some of which can act as labels in order to find their target cells.
      Exosomes also contain messages in the form of proteins and nucleic acids (RNA and
      DNA) that are transferable to target cells. Little is known and written about
      cardiac exosomes, although Gupta and Knowlton described exosomes containing HSP60
      in 2007. It is now known that exosomes from cardiomyocytes can transfect other
      cells and that the metabolic milieu of the parental cell decides the quality of
      exosomes released such that they induce differential gene expression in
      transfected cells. Future clinical use of exosomes in diagnosis, monitoring
      disease progress, and treatment is promising. 

PMID- 24436428
TI  - Exosomes: nanoparticles involved in cardioprotection?
AB  - Exosomes are nanosized lipid vesicles released from cells. They are capable of
      transferring proteins, mRNA, and miRNA between cells and, therefore, represent a
      potential means of intercellular communication. Exosomes can be proangiogenic and
      may have cardioprotective properties. In contrast, their larger cousins,
      microvesicles, seem to have generally detrimental effects that are prothrombotic
      and proinflammatory. Exosomes are released from multivesicular bodies via an
      exocytic pathway and have the potential for cell-specific targeting. This normal
      process is hijacked during various pathological conditions, such as cancer, viral
      infection, and amyloidopathies. We assess the evidence for a role of exosomes and
      microvesicles in normal cardiovascular physiology, as well as during
      cardiovascular disease. In addition to offering a potential source of
      cardiovascular biomarkers, exosomes may offer a nonimmunogenic means of
      manipulating the heart. 

PMID- 24436429
TI  - Exosomes and cardiac repair after myocardial infarction.
AB  - Myocardial infarction is a leading cause of death among all cardiovascular
      diseases. The analysis of molecular mechanisms by which the ischemic myocardium
      initiates repair and remodeling indicates that secreted soluble factors are key
      players in communication to local and distant tissues, such as bone marrow.
      Recently, actively secreted membrane vesicles, including exosomes, are being
      recognized as new candidates with important roles in intercellular and tissue
      level communication. In this review, we critically examine the emerging role of
      exosomes in local and distant microcommunication mechanisms after myocardial
      infarction. A comprehensive understanding of the role of exosomes in cardiac
      repair after myocardial infarction could bridge a major gap in knowledge of the
      repair mechanism after myocardial injury. 

PMID- 24436430
TI  - Microvesicles as cell-cell messengers in cardiovascular diseases.
AB  - Cell-cell communication has proven to be even more complex than previously
      thought since the discovery that extracellular vesicles serve as containers of
      biological information on various pathophysiological settings. Extracellular
      vesicles are classified into exosomes, microvesicles/microparticles, or apoptotic
      bodies, originating from different subcellular compartments. The cellular
      machinery controlling their formation and composition, as well as the mechanisms
      regulating their extracellular release, remain unfortunately much unknown.
      Extracellular vesicles have been found in plasma, urine, saliva, and inflammatory
      tissues. Their biomarker potential has raised significant interest in the
      cardiovascular field because the vesicle composition and microRNA content are
      specific signatures of cellular activation and injury. More than simply cell
      dust, extracellular vesicles are capable of transferring biological information
      to neighboring cells and play an active role in inflammatory diseases, including
      atherosclerosis and angiogenesis. The molecular interactions regulating these
      effects involve specific receptor activation, proteolytic enzymes, reactive
      oxygen species, or delivery of genetic information to target cells. Unraveling
      their mechanisms of action will likely open new therapeutic avenues. 

PMID- 24436431
TI  - Cardiac tissue engineering: state of the art.
AB  - The engineering of 3-dimensional (3D) heart muscles has undergone exciting
      progress for the past decade. Profound advances in human stem cell biology and
      technology, tissue engineering and material sciences, as well as
      prevascularization and in vitro assay technologies make the first clinical
      application of engineered cardiac tissues a realistic option and predict that
      cardiac tissue engineering techniques will find widespread use in the preclinical
      research and drug development in the near future. Tasks that need to be solved
      for this purpose include standardization of human myocyte production protocols,
      establishment of simple methods for the in vitro vascularization of 3D constructs
      and better maturation of myocytes, and, finally, thorough definition of the
      predictive value of these methods for preclinical safety pharmacology. The
      present article gives an overview of the present state of the art, bottlenecks,
      and perspectives of cardiac tissue engineering for cardiac repair and in vitro
      testing. 

PMID- 24436433
TI  - Vitamin D and cardiovascular disease.
AB  - Vitamin D plays a classical hormonal role in skeletal health by regulating
      calcium and phosphorus metabolism. Vitamin D metabolites also have physiological
      functions in nonskeletal tissues, where local synthesis influences regulatory
      pathways via paracrine and autocrine mechanisms. The active metabolite of vitamin
      D, 1alpha,25-dihydroxyvitamin D, binds to the vitamin D receptor that regulates
      numerous genes involved in fundamental processes of potential relevance to
      cardiovascular disease, including cell proliferation and differentiation,
      apoptosis, oxidative stress, membrane transport, matrix homeostasis, and cell
      adhesion. Vitamin D receptors have been found in all the major cardiovascular
      cell types including cardiomyocytes, arterial wall cells, and immune cells.
      Experimental studies have established a role for vitamin D metabolites in
      pathways that are integral to cardiovascular function and disease, including
      inflammation, thrombosis, and the renin-angiotensin system. Clinical studies have
      generally demonstrated an independent association between vitamin D deficiency
      and various manifestations of degenerative cardiovascular disease including
      vascular calcification. However, the role of vitamin D supplementation in the
      management of cardiovascular disease remains to be established. This review
      summarizes the clinical studies showing associations between vitamin D status and
      cardiovascular disease and the experimental studies that explore the mechanistic
      basis for these associations. 

PMID- 24436432
TI  - Regulation of Akt signaling by sirtuins: its implication in cardiac hypertrophy
      and aging.
AB  - Cardiac hypertrophy is a multifactorial disease characterized by multiple
      molecular alterations. One of these alterations is change in the activity of Akt,
      which plays a central role in regulating a variety of cellular processes ranging
      from cell survival to aging. Akt activation is mainly achieved by its binding to
      phosphatidylinositol (3,4,5)-triphosphate. This results in a conformational
      change that exposes the kinase domain of Akt for phosphorylation and activation
      by its upstream kinase, 3-phosphoinositide-dependent protein kinase 1, in the
      cell membrane. Recent studies have shown that sirtuin isoforms, silent
      information regulator (SIRT) 1, SIRT3, and SIRT6, play an essential role in the
      regulation of Akt activation. Although SIRT1 deacetylates Akt to promote
      phosphatidylinositol (3,4,5)-triphosphate binding and activation, SIRT3 controls
      reactive oxygen species-mediated Akt activation, and SIRT6 transcriptionally
      represses Akt at the level of chromatin. In the first part of this review, we
      discuss the mechanisms by which sirtuins regulate Akt activation and how they
      influence other post-translational modifications of Akt. In the latter part of
      the review, we summarize the implications of sirtuin-dependent regulation of Akt
      signaling in the control of major cellular processes such as cellular growth,
      angiogenesis, apoptosis, autophagy, and aging, which are involved in the
      initiation and progression of several diseases. 

PMID- 24436434
TI  - Causality in genetics: the gradient of genetic effects and back to Koch's
      postulates of causality.

PMID- 24436435
TI  - Does p.Q247X in TRIM63 cause human hypertrophic cardiomyopathy?
AB  - RATIONALE: Variants in TRIM63, including a nonsense mutation (p.Q247X), have been
      suggested recently to cause hypertrophic cardiomyopathy. OBJECTIVE: To verify
      pathogenicity of TRIM63 p.Q247X detected by whole-exome sequencing in a
      symptomless professional sports player seeking medical advice because of a
      prolonged QT interval found during a routine check-up. METHODS AND RESULTS:
      Clinical studies were performed in the proband and his mother, who also carried
      TRIM63 p.Q247X. No evidence of hypertrophic cardiomyopathy was found in either
      person. CONCLUSIONS: The p.Q247X variant in TRIM63 is not likely to be a highly
      penetrant variant causing hypertrophic cardiomyopathy.

PMID- 24436437
TI  - Benzodiazepines: a major component in unintentional prescription drug overdoses
      with opioid analgesics.
AB  - The misuse and abuse of prescription medications in the United States continues
      to increase despite interventions by health care professionals, regulatory, and
      law enforcement agencies. Opioid analgesics are the leading class of prescription
      drugs that have caused unintentional overdose deaths. Benzodiazepines when taken
      alone are relatively safe agents in overdose. However, a 5-fold increase in
      deaths attributed to benzodiazepines occurred from 1999 to 2009. Emergency
      department visits related to opioid analgesics increased by 111% followed by
      benzodiazepines 89%. During 2003 to 2009, the 2 prescriptions drugs with the
      highest increase in death rates were oxycodone 264.6% and alprazolam 233.8%.
      Therefore, benzodiazepines have a significant impact on prescription drug
      unintentional overdoses second only to the opioid analgesics. The combination
      prescribing of benzodiazepines and opioid analgesics commonly takes place. The
      pharmacokinetic drug interactions between benzodiazepines and opioid analgesics
      are complex. The pharmacodynamic actions of these agents differ as their combined
      effects produce significant respiratory depression. Physician and pharmacy
      shopping by patients occurs, and prescription drug-monitoring programs can
      provide important information on benzodiazepine and opioid analgesic prescribing
      patterns and patient usage. Health care professionals need to inform patients and
      work closely with regulatory agencies and legislatures to stem the increasing
      fatalities from prescription drug unintentional overdoses. 

PMID- 24436438
TI  - Risks of hydroxyethyl starch 130/0.4 in cardiac surgery.

PMID- 24436439
TI  - Potential application of temozolomide in mesenchymal stem cell-based TRAIL gene
      therapy against malignant glioma.
AB  - Because the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      selectively kills tumor cells, it is one of the most promising candidates for
      cancer treatment. TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL)
      provide targeted and prolonged delivery of TRAIL in glioma therapy. However,
      acquired resistance to TRAIL of glioma cells is a major problem to be overcome.
      We showed a potential therapy that used MSC-TRAIL combined with the
      chemotherapeutic agent temozolomide (TMZ). The antitumor effects of the
      combination with MSC-TRAIL and TMZ on human glioma cells were determined by using
      an in vitro coculture system and an in vivo experimental xenografted mouse model.
      Intracellular signaling events that are responsible for the TMZ-mediated
      sensitization to TRAIL-induced apoptosis were also evaluated. Treatment of either
      TRAIL-sensitive or -resistant human glioma cells with TMZ and MSC-TRAIL resulted
      in a significant enhancement of apoptosis compared with the administration of
      each agent alone. We demonstrated that TMZ effectively increased the sensitivity
      to TRAIL-induced apoptosis via extracellular signal-regulated kinase-mediated
      upregulation of the death receptor 5 and downregulation of antiapoptotic
      proteins, such as X-linked inhibitor of apoptosis protein and cellular FLICE
      inhibitory protein. Subsequently, this combined treatment resulted in a
      substantial increase in caspase activation. Furthermore, in vivo survival
      experiments and bioluminescence imaging analyses showed that treatment using MSC
      TRAIL combined with TMZ had greater therapeutic efficacy than did single-agent
      treatments. These results suggest that the combination of clinically relevant TMZ
      and MSC-TRAIL is a potential therapeutic strategy for improving the treatment of
      malignant gliomas. 

PMID- 24436440
TI  - Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity
      but impaired differentiation with hypoxic preconditioning.
AB  - Stem cells are promising candidate cells for regenerative applications because
      they possess high proliferative capacity and the potential to differentiate into
      other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not
      retain their proliferative and multilineage differentiative capabilities after
      prolonged ex vivo propagation. We investigated the use of hypoxia as a
      preconditioning agent and in differentiating cultures to enhance MSC function.
      Culture in 5% ambient O(2) consistently enhanced clonogenic potential of primary
      MSCs from all donors tested. We determined that enhanced clonogenicity was
      attributable to increased proliferation, increased vascular endothelial growth
      factor secretion, and increased matrix turnover. Hypoxia did not impact the
      incidence of cell death. Application of hypoxia to osteogenic cultures resulted
      in enhanced total mineral deposition, although this effect was detected only in
      MSCs preconditioned in normoxic conditions. Osteogenesis-associated genes were
      upregulated in hypoxia, and alkaline phosphatase activity was enhanced.
      Adipogenic differentiation was inhibited by exposure to hypoxia during
      differentiation. Chondrogenesis in three-dimensional pellet cultures was
      inhibited by preconditioning with hypoxia. However, in cultures expanded under
      normoxia, hypoxia applied during subsequent pellet culture enhanced
      chondrogenesis. Whereas hypoxic preconditioning appears to be an excellent way to
      expand a highly clonogenic progenitor pool, our findings suggest that it may
      blunt the differentiation potential of MSCs, compromising their utility for
      regenerative tissue engineering. Exposure to hypoxia during differentiation (post
      normoxic expansion), however, appears to result in a greater quantity of
      functional osteoblasts and chondrocytes and ultimately a larger quantity of high
      quality differentiated tissue.

PMID- 24436441
TI  - Effect of human Wharton's jelly mesenchymal stem cell paracrine signaling on
      keloid fibroblasts.
AB  - Keloid scars are abnormal benign fibroproliferative tumors with high recurrence
      rates and no current efficacious treatment. Accumulating evidence suggests that
      human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs)
      have antifibrotic properties. Paracrine signaling is considered one of the main
      underlying mechanisms behind the therapeutic effects of mesenchymal stem cells.
      However, the paracrine signaling effects of WJ-MSCs on keloids have not yet been
      reported. The aim of this study is to investigate paracrine signaling effects of
      human WJ-MSCs on keloid fibroblasts in vitro. Human umbilical cords and keloid
      skin samples were obtained, and WJ-MSCs and keloid fibroblasts were isolated and
      cultured. One-way and two-way paracrine culture systems between both cell types
      were investigated. Plasminogen activator inhibitor-I and transforming growth
      factor-beta2 (TGF-beta2) transcripts were upregulated in keloid fibroblasts
      cultured with WJ-MSC-conditioned medium (WJ-MSC-CM) and cocultured with inserts,
      while showing lower TGF-beta3 gene expression. Interleukin (IL)-6, IL-8, TGF
      beta1, and TGF-beta2 protein expression was also enhanced. The WJ-MSC-CM-treated
      keloid fibroblasts showed higher proliferation rates than their control keloid
      fibroblasts with no significant change in apoptosis rate or migration ability. In
      our culture conditions, the indirect application of WJ-MSCs on keloid fibroblasts
      may enhance their profibrotic phenotype. 

PMID- 24436442
TI  - Mesenchymal stromal cells mediate Aspergillus hyphal extract-induced allergic
      airway inflammation by inhibition of the Th17 signaling pathway.
AB  - Systemic administration of mesenchymal stromal cells (MSCs) suppresses airway
      inflammation and methacholine-induced airway hyper-responsiveness (AHR) in mouse
      models of T helper cell (Th) type 2-mediated eosinophilic allergic airway
      inflammation (AAI); however, the efficacy of MSCs in mouse models of severe Th17
      mediated neutrophilic AAI has not yet been demonstrated. We assessed MSC effects
      in a mouse model of mixed Th2/Th17 AAI produced by mucosal exposure to
      Aspergillus fumigatus hyphal extract (AHE). Following sensitization produced by
      oropharyngeal AHE administration, systemic (tail vein) administration of
      syngeneic MSCs on the first day of challenge significantly reduced acute AHR
      predominantly through reduction of Th17-mediated airway inflammation. In parallel
      experiments, MSCs also mitigated AHR when administered during recurrent challenge
      10 weeks after initial sensitization and challenge through reduction in systemic
      Th17-mediated inflammation. Investigation into potential mechanistic actions of
      MSCs in this model demonstrated that although T regulatory cells were increased
      in all AHE-treated mice, MSC administration did not alter T regulatory cell
      numbers in either the acute or recurrent model. Differential induction of
      interleukin-17a secretion was observed in ex vivo restimulation of mediastinal
      lymph node mixed-cell cytokine analyses. Although the mechanisms by which MSCs
      act to decrease inflammation and AHR in this model are not yet fully elucidated,
      decrease in Th17-mediated airway inflammation appears to play a significant role.
      These results provide a basis for further investigations of MSC administration as
      a potential therapeutic approach for severe refractory neutrophilic asthma. 

PMID- 24436443
TI  - Amide-type local anesthetics and human mesenchymal stem cells: clinical
      implications for stem cell therapy.
AB  - In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are
      gaining attention as a cell source for the repair and regeneration of tissues
      spanning an array of medical disciplines. In orthopedics, hMSCs are often
      delivered in a site-specific manner at the area of interest and may require the
      concurrent application of local anesthetics (LAs). To address the implications of
      using hMSCs in combination with anesthetics for intra-articular applications, we
      investigated the effect that clinically relevant doses of amide-type LAs have on
      the viability of bone marrow-derived hMSCs and began to characterize the
      mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from
      three donors were exposed to the amide-type LAs ropivacaine, lidocaine,
      bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once
      injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%,
      and 50% of the stock solution and incubated with each hMSC line for 40 minutes,
      120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays
      were performed. We found that extended treatment with LAs for 24 hours had a
      significant impact on both hMSC viability and adhesion. In addition, hMSC
      treatment with three of the four anesthetics resulted in cell death via apoptosis
      following brief exposures. Ultimately, we concluded that amide-type LAs induce
      hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical
      outcomes, following a similar trend that has been established between these
      particular anesthetics and articular chondrocytes both in vitro and in vivo. 

PMID- 24436444
TI  - Tomography and blood vessels in Hughes syndrome.
AB  - Antiphospholipid antibody syndrome (APS) or Hughes syndrome is a multisystem
      autoimmune disorder that is characterized by venous and arterial thrombosis
      and/or pregnancy complications (miscarriage and fetal death, preeclampsia,
      placental insufficiency, and fetal growth restriction), and positive serologic
      tests for anticardiolipin antibodies (aCL), lupus anticoagulant (LA), or
      antibodies against beta2-glycoprotein I (anti-beta2GPI) either of IgG or IgM
      isotype. APS is characterized by accelerated atherosclerosis that, together with
      an increased tendency toward thrombosis, leads to the occurrence of various
      vascular events. Timely diagnosis of vascular changes, preferably in the
      subclinical phase, is required both because of their severity and the high
      mortality rate. Detection of arterial and venous changes is performed by various
      invasive and noninvasive diagnostic methods. Computed tomographic angiography
      (CTA) seems to be the most precise method with low exposure time, giving
      clinicians an opportunity for early diagnosis and timely treatment of APS
      patients.

PMID- 24436445
TI  - Meta-analysis of contrast-enhanced ultrasound for the differentiation of benign
      and malignant breast lesions.
AB  - BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a non-invasive method for the
      assessment of breast lesions. The accuracy of CEUS in diagnosing of breast cancer
      has never been systematically assessed. PURPOSE: To determine the overall
      performance of CEUS in the differentiation of benign and malignant breast lesions
      using meta-analysis. MATERIAL AND METHODS: PubMed, Embase, Cochrane Library, and
      article references published before October 2012 were searched. Published studies
      that used histopathologic results as golden reference to assess the diagnostic
      performance of CEUS in patients suspected of having breast cancer and the data
      necessary to calculate the diagnostic results were included. The qualities of
      eligible studies for final meta-analysis were assessed by using the quality
      assessment of diagnostic studies (QUADAS) instrument. Sensitivity, specificity,
      summary receiver-operating characteristic (sROC) curves, and area under the curve
      were calculated to examine the diagnostic performance of CEUS. RESULTS: Of 16
      eligible studies, 957 breast lesions were included in the original meta-analysis,
      among which heterogeneity arising from factors other than threshold effect was
      explored. Meta-regression analysis confirmed the contrast agent was the most
      significant factor cause of heterogeneity (P = 0.0012, relative diagnostic odds
      ratio [DOR] = 7.06). The use of perfluoro containing microbubbles (Sonovue or
      Optison) significantly increased the diagnostic precision compared with Levovist.
      The pooled weighted estimates of sensitivity and specificity for CEUS in the
      diagnosis of breast lesions were 0.86 (95% confidence interval [CI], 0.83, 0.89)
      and 0.79 (95% CI, 0.75, 0.83), respectively. CONCLUSION: CEUS has good
      sensitivity and specificity in the characterization of breast lesions and can
      potentially help to select suspicious breast mass for surgery.

PMID- 24436446
TI  - The use of z scores in probabilistic sensitivity analyses.

PMID- 24436447
TI  - The life table method of half cycle correction: getting it right.

PMID- 24436448
TI  - Abdominoplasty-related nerve injuries: systematic review and treatment options.
AB  - BACKGROUND: Abdominoplasty is a common cosmetic procedure; nerve injury is an
      underexplored risk of the procedure. OBJECTIVE: The authors review existing
      literature to examine the incidence and treatment of nerve injuries after
      abdominoplasty procedures and provide a treatment algorithm based on their
      results. METHODS: A search of the literature on MEDLINE, EMBASE, and the Cochrane
      Database of Systematic Reviews was undertaken. After full-text review, 23
      articles met our criteria. Any mentions of nerve injury, including references to
      a lack of nerve injury, were documented. All data were pooled for analysis. From
      our combined data, we calculated the risks of postabdominoplasty nerve injury by
      dividing the total number of nerve injuries by the total number of patients.
      RESULTS: Pooled data showed that 1.94% of patients sustained specific nerve
      injury, and 1.02% of patients sustained permanent injury after abdominoplasty. In
      addition, 7.67% experienced decreased sensation, 1.07% reported chronic pain, and
      0.44% reported temporary weakness or paralysis. Nerves directly injured were the
      lateral femoral cutaneous (1.36% of patients) and iliohypogastric (0.10%) nerves.
      Nerves injured from surgical positioning were the brachial plexus (0.10%),
      musculocutaneous (0.10%), radial (0.05%), sciatic (0.19%), and common peroneal
      (0.05%) nerves. CONCLUSIONS: Although our results showed a low incidence of
      postabdominoplasty nerve injury, the lasting impact on affected patients' quality
      of life can be significant. Appropriate and timely treatment by a
      multidisciplinary team is critical to optimize patient outcomes. Better reporting
      of nerve injuries in future studies of abdominoplasty will provide more accurate
      information about the incidence and consequences of these injuries. LEVEL OF
      EVIDENCE: 4.

PMID- 24436449
TI  - Antibiotic treatment suppresses rotavirus infection and enhances specific humoral
      immunity.
AB  - BACKGROUND: Rotavirus causes 500 000 deaths and millions of physician visits and
      hospitalizations per year, with worse outcomes and reduced vaccine efficacy in
      developing countries. We hypothesized that the gut microbiota might modulate
      rotavirus infection and/or antibody response and thus potentially play a role in
      such regional differences. METHODS: The microbiota was ablated via germ-free or
      antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose
      dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was
      assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse
      transcription polymerase chain reaction. Diarrhea was scored visually. Humoral
      responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent
      spot assay. RESULTS: Microbiota elimination delayed infection and reduced
      infectivity by 42%. Antibiotics did not alter ratios of positive-sense to
      negative-sense strands, suggesting that entry rather than replication was
      influenced. Antibiotics reduced the diarrhea incidence and duration, indicating
      that the reduction in the level of rotavirus antigen was biologically
      significant. Despite lowered antigen level, antibiotics resulted in a more
      durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody
      response durability correlated with increased small intestinal rotavirus
      specific, immunoglobulin A-producing antibody-secreting cell concentration in
      antibiotic-treated mice. Conversely, DSS treatment impaired generation of
      rotavirus-specific antibodies. CONCLUSIONS: Microbiota ablation resulted in
      reduced rotavirus infection/diarrhea and a more durable rotavirus antibody
      response, suggesting that antibiotic administration before rotavirus vaccination
      could raise low seroconversion rates that correlate with the vaccine's inefficacy
      in developing regions.

PMID- 24436450
TI  - Hepatitis E virus reinfections in solid-organ-transplant recipients can evolve
      into chronic infections.
AB  - BACKGROUND: Hepatitis E virus (HEV) infections are a major cause of acute
      hepatitis in developing and industrialized countries. Little is known about anti
      HEV immunity in solid-organ recipients. METHODS: We screened 263 solid-organ
      recipients for anti-HEV immunoglobulin G (IgG) at transplantation. They were
      followed up for 1 year and tested for HEV RNA and anti-HEV antibodies 1 year
      after transplantation and if their liver enzyme activities increased. RESULTS: A
      total of 38.4% had anti-HEV IgG at transplantation. The mean concentrations (+/
      SD) of anti-HEV IgG at transplantation (8 +/- 17.5 U/mL) and 1 year later (6.4 +/
      12.0 U/mL, P = .4) were similar. There were 3 de novo HEV infections during the
      1-year follow-up among patients who were HEV seronegative before transplantation,
      giving an annual incidence of 2.1%. We also identified 3 HEV reinfections among
      patients who were seropositive before transplantation through detection of HEV
      RNA, for an annual incidence of 3.3%. Their anti-HEV IgG concentrations were 0.3,
      2.1, and 6.2 World Health Organization (WHO) units/mL before transplantation.
      Reinfection of the patient with the lowest IgG concentration at transplantation
      had evolved to a chronic infection. CONCLUSIONS: Low anti-HEV antibodies (<7 WHO
      units/mL) seemed not to protect solid-organ recipients. HEV reinfection in
      immunocompromised patients can lead to chronic infection, as in primary
      infections.

PMID- 24436451
TI  - Mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a
      well-characterized human genital organ culture.
AB  - We developed and morphologically characterized a human genital mucosa explant
      model (endocervix and ectocervix/vagina) to mimic genital herpes infections
      caused by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequent analysis
      of HSV entry receptor expression throughout the menstrual cycle in genital
      tissues was performed, and the evolution of HSV-1/-2 mucosal spread over time was
      assessed. Nectin-1 and -2 were expressed in all tissues during the entire
      menstrual cycle. Herpesvirus entry mediator expression was limited mainly to some
      connective tissue cells. Both HSV-1 and HSV-2 exhibited a plaque-wise mucosal
      spread across the basement membrane and induced prominent epithelial syncytia. 

PMID- 24436452
TI  - Use of an Sm-p80-based therapeutic vaccine to kill established adult schistosome
      parasites in chronically infected baboons.
AB  - No vaccines are available for human use for any parasitic infections, including
      the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma
      mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine.
      Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a
      variety of vaccine approaches in both rodent and nonhuman primate models.
      However, the therapeutic efficacy of a Sm-p80-based vaccine had not been
      determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by
      using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons.
      Vaccine formulations were able to decrease established adult worms by 10%-36%,
      reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in
      feces by 13%-33%, compared with control formulations. Marked differences were
      observed in B and T cell immune correlates between vaccinated and control
      animals. This is the first report of killing of established adult schistosome
      worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this
      study adds to the evidence that Sm-p80 is a potentially important antigen with
      both substantial prophylactic and therapeutic efficacies. These data reinforce
      that Sm-p80 should be moved forward along the path toward human clinical trials. 

PMID- 24436453
TI  - Sensitive tenofovir resistance screening of HIV-1 from the genital and blood
      compartments of women with breakthrough infections in the CAPRISA 004 tenofovir
      gel trial.
AB  - The Centre for the AIDS Programme of Research in South Africa 004 (CAPRISA 004)
      study demonstrated that vaginally applied tenofovir gel is a promising
      intervention for protecting women from sexually acquiring human immunodeficiency
      virus (HIV). However, the potential for emergence of tenofovir resistance remains
      a concern in women who seroconvert while using the gel despite the lack of plasma
      virus resistance as assessed by population sequencing during the trial. We
      applied highly sensitive polymerase chain reaction-based assays to screen for
      tenofovir resistance in plasma and vaginal swab specimens. The absence of
      mutation detection suggested little immediate risk of tenofovir-resistant HIV-1
      emergence and forward transmission in settings in which gel users are closely
      monitored for HIV seroconversion. 

PMID- 24436454
TI  - A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given
      at 4.5 months of age: effect on total hospital admissions.
AB  - Observational studies and trials from low-income countries indicate that measles
      vaccine has beneficial nonspecific effects, protecting against non-measles
      related mortality. It is not known whether measles vaccine protects against
      hospital admissions. Between 2003 and 2007, 6417 children who had received the
      third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned
      to receive measles vaccine at 4.5 months or no measles vaccine; all children were
      offered measles vaccine at 9 months of age. Using hospital admission data from
      the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates
      between enrollment and the 9-month vaccination in Cox models, providing admission
      hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All
      analyses were conducted stratified by sex and reception of neonatal vitamin A
      supplementation (NVAS). Before enrollment the 2 groups had similar admission
      rates. Following enrollment, the measles vaccine group had an admission HRR of
      0.70 (95% confidence interval [CI], .52-.95), with a ratio of 0.53 (95% CI, .32
      .86) for girls and 0.86 (95% CI, .58-1.26) for boys. For children who had not
      received NVAS, the admission HRR was 0.53 (95% CI, .34-.84), with an effect of
      0.30 (95% CI, .13-.70) for girls and 0.73 (95% CI, .42-1.28) for boys (P = .08,
      interaction test). The reduction in admissions was separately significant for
      measles infection (admission HRR, 0 [95% CI, 0-.24]) and respiratory infections
      (admission HRR, 0.37 [95% CI, .16-.89]). Early measles vaccine may have major
      benefits for infant morbidity patterns and healthcare costs. Clinical trials
      registration NCT00168558. 

PMID- 24436455
TI  - Immunotherapies influence the influenza vaccination response in multiple
      sclerosis patients: an explorative study.
AB  - BACKGROUND: The immunogenicity of influenza vaccines in MS patients undergoing
      immunomodulatory treatment is not well studied. OBJECTIVES: This explorative
      study investigated the influence of immunomodulatory treatment on MS patients
      receiving pandemic H1N1 (swine flu) vaccination in 2009 and seasonal influenza
      vaccination in 2010. METHODS: We investigated the immune response to pandemic
      H1N1 vaccination among 113 MS patients and 216 controls during the pandemic of
      2009. We also investigated the serological response to seasonal influenza
      vaccination (2010 - 2011 season) among 49 vaccinated and 62 non-vaccinated MS
      patients, versus 73 controls. We evaluated these vaccine responses by
      haemagglutination inhibition assay. RESULTS: MS patients receiving
      immunomodulatory treatment had reduced protection (27.4%), compared to controls
      (43.5%) (p = 0.006), after pandemic H1N1 vaccination (2009). The rates of
      protection were not influenced by interferon beta treatment (44.4% protected),
      but were reduced among patients receiving glatiramer acetate (21.6%), natalizumab
      (23.5%), and mitoxantrone (0.0%). A similar pattern emerged after MS patients
      received a seasonal influenza vaccination in 2010. CONCLUSIONS: These findings
      suggest that MS patients receiving immunomodulatory therapies other than
      interferon beta should be considered for a vaccine response analysis and perhaps
      be offered a second dose of the vaccine, in cases of insufficient protection.

PMID- 24436456
TI  - Use of Rasch analysis to refine a patient-reported questionnaire on satisfaction
      with communication of the multiple sclerosis diagnosis.
AB  - BACKGROUND: The Comunicazione medico-paziente nella Sclerosi Multipla - Revised
      (COSM-R) is a patient self-assessed questionnaire probing the moment of multiple
      sclerosis (MS) diagnosis disclosure (section 1, five items) and following period
      (section 2, 15 items). OBJECTIVES: This study examined COSM-R dimensionality and
      measurement properties through Rasch analysis (partial-credit model) and proposed
      a revised questionnaire. METHODS: Cross-sectional COSM-R data were obtained from
      1068 people with MS (PwMS, 1065 questionnaires) participating in four studies
      (102 centres). Mean age was 40 years (range 17-73); 70% were women; 53% were from
      Northern, 25% from Central, and 21% from Southern Italy. RESULTS:
      Unidimensionality was not confirmed for COSM-R section 1, but was for section 2
      after removal of three items. The revised instrument (COSM-S, Shortened)
      consisted of the original five-item checklist (section 1), modified by removing
      the table grouping of three items, and 12 of the original 15 section 2 items,
      which could now be summed and transformed into an interval scale. Scores were
      higher for items assessing emotional satisfaction than for those assessing
      informational satisfaction. CONCLUSIONS: The proposed COSM-S is a composite
      measure of satisfaction with MS diagnosis communication with improved metric
      properties over the original COSM-R, and whose section 2 satisfies Rasch model
      expectations.

PMID- 24436457
TI  - Use of propofol-containing versus benzodiazepine regimens for alcohol withdrawal
      requiring mechanical ventilation.
AB  - BACKGROUND: When chronic, excessive alcohol intake is abruptly halted, patients
      are at risk for developing life-threatening alcohol withdrawal syndrome (AWS).
      Benzodiazepines have established efficacy, yet some patients' symptoms persist
      despite treatment with high doses. OBJECTIVES: The study objective was to compare
      time to resolution of AWS symptoms in mechanically ventilated patients receiving
      propofol-containing versus benzodiazepine infusions. METHODS: This study was a
      retrospective cohort analysis of adult patients with ICD-9 codes for AWS who
      required mechanical ventilation for AWS symptoms. RESULTS: A total of 1637
      records were reviewed, and 64 were included. Propofol-containing regimens were
      used in 46 cases (72%), whereas benzodiazepine infusion monotherapy accounted for
      18 cases (28%). Patients were predominantly male (97%), with a mean age of 45
      years. Lorazepam-equivalent benzodiazepine doses given prior to intubation were
      greater in patients receiving propofol infusion (56 vs 15 mg, P = .03). Time to
      resolution of AWS symptoms for propofol- and benzodiazepine-treated patients was
      8 and 7 days, respectively (P = .34). Median hospital and intensive care unit
      lengths of stay were similar (9 vs 10 days and 4 vs 4 days, respectively; P > .05
      for both comparisons), as were days of mechanical ventilation (4 vs 3 days, P =
      .98). Patients in the benzodiazepine infusion monotherapy group required
      numerically increased amounts of benzodiazepine bolus doses while on continuous
      sedation, compared with patients receiving propofol infusion (36 vs 10 mg, P =
      .06). CONCLUSIONS: Propofol and Benzodiazepine-treated patients with AWS
      requiring mechanical ventilation experienced similar days of AWS symptoms, length
      of stay, and mechanical ventilation.

PMID- 24436458
TI  - Efficacy of a Creon delayed-release pancreatic enzyme protocol for clearing
      occluded enteral feeding tubes.
AB  - BACKGROUND: Alkalinized Viokase pancreatic enzyme tablets restored patency to
      71.9% of occluded Dobhoff tubes in a prospective study. After removal of Viokase
      tablets from the US market, the hospital protocol for unclogging enteral feeding
      tubes was adapted to use Creon pancreatic enzyme delayed-release capsules,
      despite the lack of published data. OBJECTIVE: To evaluate the effectiveness of a
      Creon-based protocol to clear occluded enteral feeding tubes. METHODS: This
      retrospective study included all adult and pediatric patients seen in the
      emergency department or in an inpatient setting who received Creon 12 000 units
      lipase delayed-release capsule dissolved in a solution of sodium bicarbonate 650
      mg and sterile water for clearing occluded enteral feeding tubes between May 1
      and November 30, 2010. The Creon protocol was deemed effective if tube clearance
      was documented in the medical record or if enteral feedings were resumed with no
      note regarding tube replacement. RESULTS: Alkalinized Creon delayed-release
      capsules were administered to 83 patients with a total of 118 clogged tubes.
      Three poorly documented cases and 5 tubes with mechanical clogs were excluded
      from data analysis. Patency was restored to 53 of 110 (48.2%) occluded tubes.
      More than 1 treatment course was attempted in 5 cases, with success in 3.
      CONCLUSION: An alkalinized Creon pancreatic enzyme protocol was effective in
      clearing approximately half of the occluded enteral feeding tubes in this
      retrospective study, an efficacy rate much less than that previously reported in
      the literature with a Viokase-based protocol.

PMID- 24436459
TI  - Dendritic cell membrane CD83 enhances immune responses by boosting intracellular
      calcium release in T lymphocytes.
AB  - CD83 is a marker of mDCs directly related to their lymphostimulatory ability.
      Some data suggest that it has a central role in the immune system regulation, but
      how this function is performed remains to be determined. This work aimed to
      analyze the influence of CD83, present in mDCs, in the modulation of calcium
      signaling in T lymphocytes. Mo were differentiated into iDCs and activated with
      TNF-alpha. iDCs were treated, 4 h before activation, with siRNACD83, to reduce
      CD83 expression. Purified allogeneic T lymphocytes were labeled with the calcium
      indicator Fluo-4-AM, and calcium mobilization in the presence of mDCs was
      analyzed. CD83 knockdown mDCs induced lower calcium signal amplitude in T
      lymphocytes (29.0+/-10.0) compared with siRNAscr-treated mDCs (45.5+/-5.3). In
      another set of experiments, surface mDC CD83 was blocked with a specific mAb, and
      again, decreased calcium signaling in T lymphocytes was detected by flow
      cytometry and microscopy (fluorescence and confocal). In the presence of
      antibody, the percentage of responding T cells was reduced from 58.14% to 34.29%.
      As expected, anti-CD83 antibodies also reduced the proliferation of T lymphocytes
      (as assessed by CFSE dilution). Finally, in the absence of extracellular calcium,
      CD83 antibodies abrogated T cell signaling induced by allogeneic mDCs, suggesting
      that the presence of CD83 in mDC membranes enhances T lymphocyte proliferation by
      boosting calcium release from intracellular stores in these cells.

PMID- 24436460
TI  - Good research, good evidence, and good nursing practice: a virtuous circle.

PMID- 24436461
TI  - Measuring CSF flow dynamics in spontaneous intracranial hypotension with phase
      contrast magnetic resonance imaging: Potential implications for diagnosis and
      treatment.

PMID- 24436462
TI  - Nutraceuticals for the prevention of migraine in children: Do we know what the
      benefits and the risks are?

PMID- 24436463
TI  - The incidence of premalignant and malignant disease in Reinke's edema.
AB  - Reinke's edema is a benign lesion of the vocal folds affecting the subepithelial
      space. As part of a study of the management of Reinke's edema, we aimed to
      determine the prevalence of dysplasia and malignancy in histologically proven
      Reinke's edema. A retrospective analysis of all laryngeal biopsies performed in
      north Glasgow, United Kingdom, between 2001 and 2010 was carried out. Clinical
      and pathological data from patients with histologically confirmed Reinke's edema
      were recorded with specific respect to the reporting of dysplasia and malignancy.
      From the 10-year cohort, a total of 3902 laryngeal biopsies were performed. In
      total, 189 patients (18 males and 171 females) had histologically proven Reinke's
      edema. Of this cohort, 170 (90%) had no dysplasia, 16 (8%) had mild dysplasia, 2
      (1%) had moderate dysplasia, and 1 (<1%) had severe dysplasia. There was no
      malignancy reported. In our predominantly female smoking population, the
      epithelium appears to differentiate to benign Reinke's edema rather than
      malignancy. Patients can be reassured with regard to the low risk of malignancy
      in classic Reinke's edema. 

PMID- 24436464
TI  - A frailty index identifies patients at high risk of mortality after tracheostomy.
AB  - OBJECTIVE: To evaluate the utility of a modified frailty index as an indicator of
      postoperative mortality in patients undergoing tracheostomy. STUDY DESIGN: Case
      series with chart review. SETTING: Tertiary care veterans hospital. SUBJECTS AND
      METHODS: A chart review was conducted of consecutive tracheostomies performed
      between April 2007 and September 2012. A modified frailty index consisting of 11
      items based on the Revised Minimum Data Set Mortality Rating Index (MMRI-R) was
      retrospectively applied using the patient's status immediately prior to
      tracheostomy. The resultant 6-month calculated mortality risk was compared with
      both the Veterans Health Administration Surgical Quality Improvement Program's
      (VASQIP) 30-day calculated mortality and actual mortality. RESULTS: One hundred
      consecutive tracheostomies were analyzed. No patients were excluded. Sixty-nine
      patients died within the study period, with 1-, 6-, and 12-month mortality rates
      of 25%, 43%, and 59%, respectively. The average calculated 6-month mortality risk
      using the modified frailty index was 40.5% for nonsurvivors compared with 25.4%
      for survivors (P = .001). Both the VASQIP calculator and modified frailty index
      differentiated mortality risks between patients without head and neck cancer who
      survived less than 6 months versus those who survived longer than 6 months (P =
      .006 and .01). However, neither the VASQIP nor the modified frailty index
      differentiated mortality risks for head and neck cancer patients who survived
      less than 6 months versus greater than 6 months (P = .94 and .26). CONCLUSION: A
      modified frailty index identifies patients without head and neck cancer at high
      risk of postoperative mortality after tracheostomy.

PMID- 24436465
TI  - Heptanol application to the mouse round window: a model for studying cochlear
      lateral wall regeneration.
AB  - OBJECTIVE: Identify cells supporting cochlear lateral wall regeneration. STUDY
      DESIGN: Prospective controlled trial. SETTING: Laboratory. Human presbyacusis
      occurs, in part, secondary to age-related degeneration of cochlear lateral wall
      structures such as the stria vascularis and spiral ligament fibrocytes. This
      degeneration is likely linked to the diminished regenerative capacity of lateral
      wall cells with age. While lateral wall regeneration is known to occur after an
      acute insult, this process remains poorly understood and the cells capable of
      self-replication unidentified. We hypothesized that spiral ligament fibrocytes
      constitute these proliferative cells. SUBJECTS AND METHODS: To test the
      hypothesis, an acute ototoxic insult was created in 65 normal-hearing, young
      adult mice via cochlear exposure to heptanol. Sacrifice occurred at 1 to 60 days
      posttreatment. Auditory brainstem responses, 5-ethynyl-2'-deoxyuridine assay, and
      immunostaining were used to assess regeneration. RESULTS: Posttreatment hearing
      thresholds were elevated in nearly all treated mice. Selective fibrocyte
      apoptosis and strial injury were observed at the time of peak hearing loss around
      1 to 7 days posttreatment. Cellular proliferation was detected in the region of
      type II fibrocytes during this time. Hearing thresholds plateaued at 7 days
      posttreatment followed by a significant recovery of both hearing and morphologic
      appearance. Permanent outer hair cell degeneration was observed. CONCLUSIONS:
      Heptanol application to the round window of young adult mice is a rapid,
      selective, and reliable technique for investigating proliferation in the cochlear
      lateral wall. The data indirectly showed that spiral ligament fibrocytes may be
      the proliferative cells of the cochlear lateral wall. Further studies of this
      process are needed.

PMID- 24436466
TI  - Swallowing disorders in the ambulatory medical setting.
AB  - OBJECTIVES: The aims of this cross-sectional study were to explore the nationwide
      number and demographics of patient visits due to dysphagia and to investigate
      potential differences in their management between otolaryngologists and other
      physicians in the outpatient setting. STUDY DESIGN: Cross-sectional. SETTING:
      National Ambulatory Medical Care Survey. SUBJECTS AND METHODS: The data sets from
      2007 to 2010 were queried to extract all cases with dysphagia as a reason for
      visit. Data regarding demographics, imaging studies, nonmedication therapies,
      diagnoses, medications, and patient disposition were compared between
      otolaryngologists, primary care physicians, and other specialists. RESULTS:
      Annually, 1,875,187 (95% confidence interval [CI], 1,443,876-2,307,204)
      outpatient visits were due to dysphagia, comprising 0.19% of all visits (95% CI,
      0.14%-0.23%) and 1.55% (95% CI, 1.10%-2.0%) of the visits to otolaryngologists.
      The visits were mostly distributed between primary care physicians and other
      specialists, while 16.4% (95% CI, 11.3%-21.6%) visited an otolaryngology office.
      Otolaryngologists, primary care physicians, and other specialists ordered imaging
      studies in 22.8%, 10.2%, and 24.0% (P = .02); performed aerodigestive-specific
      procedures in 20.8%, 4.0%, and 36.2% (P < .0001); and referred the patient to
      another physician in 5.8%, 14.8%, and 2.8% (P = .003) of the visits,
      respectively. CONCLUSIONS: Almost 0.2% of office visits to physicians have a
      complaint of dysphagia. Otolaryngologists are involved in the care of a minority
      of these visits. The differences in the management of dysphagic patients may be
      due to different etiologies of the disease.

PMID- 24436467
TI  - Total laryngeal transplant explanted: 14 years of lessons learned.
AB  - In 1998, the first successful total laryngeal transplant was performed.
      Outstanding voice quality and swallowing function were achieved, and over the
      subsequent 14 years, much was learned about tolerance of a transplanted larynx.
      After approximately a decade, a slowly progressive, chronic rejection process
      gradually rendered the organ nonfunctional, and the patient and his providers
      deemed him appropriate for explantation. This is a report of the clinical
      indications and outcome surrounding the explantation of the first successful
      total laryngeal transplant. 

PMID- 24436468
TI  - Global analysis reveals the complexity of the human glomerular extracellular
      matrix.
AB  - The glomerulus contains unique cellular and extracellular matrix (ECM)
      components, which are required for intact barrier function. Studies of the
      cellular components have helped to build understanding of glomerular disease;
      however, the full composition and regulation of glomerular ECM remains poorly
      understood. We used mass spectrometry-based proteomics of enriched ECM extracts
      for a global analysis of human glomerular ECM in vivo and identified a tissue
      specific proteome of 144 structural and regulatory ECM proteins. This catalog
      includes all previously identified glomerular components plus many new and
      abundant components. Relative protein quantification showed a dominance of
      collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with
      abundant collagen VI and TINAGL1. Protein network analysis enabled the creation
      of a glomerular ECM interactome, which revealed a core of highly connected
      structural components. More than one half of the glomerular ECM proteome was
      validated using colocalization studies and data from the Human Protein Atlas.
      This study yields the greatest number of ECM proteins relative to previous
      investigations of whole glomerular extracts, highlighting the importance of
      sample enrichment. It also shows that the composition of glomerular ECM is far
      more complex than previously appreciated and suggests that many more ECM
      components may contribute to glomerular development and disease processes. The
      mass spectrometry proteomics data have been deposited to the ProteomeXchange
      Consortium with the dataset identifier PXD000456.

PMID- 24436469
TI  - Glomerular cell cross-talk influences composition and assembly of extracellular
      matrix.
AB  - The glomerular basement membrane (GBM) is a specialized extracellular matrix
      (ECM) compartment within the glomerulus that contains tissue-restricted isoforms
      of collagen IV and laminin. It is integral to the capillary wall and therefore,
      functionally linked to glomerular filtration. Although the composition of the GBM
      has been investigated with global and candidate-based approaches, the relative
      contributions of glomerular cell types to the production of ECM are not well
      understood. To characterize specific cellular contributions to the GBM, we used
      mass spectrometry-based proteomics to analyze ECM isolated from podocytes and
      glomerular endothelial cells in vitro. These analyses identified cell type
      specific differences in ECM composition, indicating distinct contributions to
      glomerular ECM assembly. Coculture of podocytes and endothelial cells resulted in
      an altered composition and organization of ECM compared with monoculture ECMs,
      and electron microscopy revealed basement membrane-like ECM deposition between
      cocultured cells, suggesting the involvement of cell-cell cross-talk in the
      production of glomerular ECM. Notably, compared with monoculture ECM proteomes,
      the coculture ECM proteome better resembled a tissue-derived glomerular ECM
      dataset, indicating its relevance to GBM in vivo. Protein network analyses
      revealed a common core of 35 highly connected structural ECM proteins that may be
      important for glomerular ECM assembly. Overall, these findings show the
      complexity of the glomerular ECM and suggest that both ECM composition and
      organization are context-dependent.

PMID- 24436470
TI  - Geographic determinants of access to pediatric deceased donor kidney
      transplantation.
AB  - Children receive priority in the allocation of deceased donor kidneys for
      transplantation in the United States, but because allocation begins locally,
      geographic differences in population and organ supply may enable variation in
      pediatric access to transplantation. We assembled a cohort of 3764 individual
      listings for pediatric kidney transplantation in 2005-2010. For each donor
      service area, we assigned a category of short (<180 days), medium (181-270 days),
      or long (>270 days) median waiting time and calculated the ratio of pediatric
      quality kidneys to pediatric candidates and the percentage of these kidneys
      locally diverted to adults. We used multivariable Cox regression analyses to
      examine the association between donor service area characteristics and time to
      deceased donor kidney transplantation. The Kaplan-Meier estimate of median
      waiting time to transplantation was 284 days (95% confidence interval, 263 to 300
      days) and varied from 14 to 1313 days across donor service areas. Overall, 29% of
      pediatric-quality kidneys were locally diverted to adults. Compared with areas
      with short waiting times, areas with long waiting times had a lower ratio of
      pediatric-quality kidneys to candidates (3.1 versus 5.9; P<0.001) and more
      diversions to adults (31% versus 27%; P<0.001). In multivariable regression, a
      lower kidney to candidate ratio remained associated with longer waiting time
      (hazard ratio, 0.56 for areas with <2:1 versus reference areas with >=5:1
      kidneys/candidates; P<0.01). Large geographic variation in waiting time for
      pediatric deceased donor kidney transplantation exists and is highly associated
      with local supply and demand factors. Future organ allocation policy should
      address this geographic inequity. 

PMID- 24436471
TI  - Na+/H+ exchanger regulatory factor 3 is critical for multidrug resistance protein
      4-mediated drug efflux in the kidney.
AB  - Na(+)/H(+) exchanger regulatory factor 3 (NHERF3) is a PSD-95/discs large/ZO-1
      (PDZ)-based adaptor protein that regulates several membrane-transporting proteins
      in epithelia. However, the in vivo physiologic role of NHERF3 in transepithelial
      transport remains poorly understood. Multidrug resistance protein 4 (MRP4) is an
      ATP binding cassette transporter that mediates the efflux of organic molecules,
      such as nucleoside analogs, in the gastrointestinal and renal epithelia. Here, we
      report that Nherf3 knockout (Nherf3(-/-)) mice exhibit profound reductions in
      Mrp4 expression and Mrp4-mediated drug transport in the kidney. A search for the
      binding partners of the COOH-terminal PDZ binding motif of MRP4 among several
      epithelial PDZ proteins indicated that MRP4 associated most strongly with NHERF3.
      When expressed in HEK293 cells, NHERF3 increased membrane expression of MRP4 by
      reducing internalization of cell surface MRP4 and consequently, augmented MRP4
      mediated efflux of adefovir, a nucleoside-based antiviral agent and well known
      substrate of MRP4. Examination of wild-type and Nherf3(-/-) mice revealed that
      Nherf3 is most abundantly expressed in the kidney and has a prominent role in
      modulating Mrp4 levels. Deletion of Nherf3 in mice caused a profound reduction in
      Mrp4 expression at the apical membrane of renal proximal tubules and evoked a
      significant increase in the plasma and kidney concentrations of adefovir, with a
      corresponding decrease in the systemic clearance of this drug. These results
      suggest that NHERF3 is a key regulator of organic transport in the kidney,
      particularly MRP4-mediated clearance of drug molecules. 

PMID- 24436472
TI  - Technical requirements for Na18F PET bone imaging of patients being treated using
      a Taylor spatial frame.
AB  - Diagnosis of new bone growth in patients with compound tibia fractures or
      deformities treated using a Taylor spatial frame is difficult with conventional
      radiography because the frame obstructs the images and creates artifacts. The use
      of Na(18)F PET studies may help to eliminate this difficulty. METHODS: Patients
      were positioned on the pallet of a clinical PET/CT scanner and made as
      comfortable as possible with their legs immobilized. One bed position covering
      the site of the fracture, including the Taylor spatial frame, was chosen for the
      study. A topogram was performed, as well as diagnostic and attenuation correction
      CT. The patients were given 2 MBq of Na(18)F per kilogram of body weight. A 45
      min list-mode acquisition was performed starting at the time of injection,
      followed by a 5-min static acquisition 60 min after injection. The patients were
      examined 6 wk after the Taylor spatial frame had been applied and again at 3 mo
      to assess new bone growth. RESULTS: A list-mode reconstruction sequence of 1 *
      1,800 and 1 * 2,700 s, as well as the 5-min static scan, allowed visualization of
      regional bone turnover. CONCLUSION: With Na(18)F PET/CT, it was possible to
      confirm regional bone turnover as a means of visualizing bone remodeling without
      the interference of artifacts from the Taylor spatial frame. Furthermore, dynamic
      list-mode acquisition allowed different sequences to be performed, enabling, for
      example, visualization of tracer transport from blood to the fracture site.

PMID- 24436474
TI  - "Quitting smoking will benefit your health": the evolution of clinician messaging
      to encourage tobacco cessation.
AB  - Illnesses that are caused by smoking remain as the world's leading cause of
      preventable death. Smoking and tobacco use constitute approximately 30% of all
      cancer-related deaths and nearly 90% of lung cancer-related deaths. Thus,
      improving smoking cessation interventions is crucial to reduce tobacco use and
      assist in minimizing the burden of cancer and other diseases in the United
      States. This review focuses on the existing research on framed messages to
      promote smoking cessation. Consistent with the tenets of prospect theory and
      recent meta-analysis, gain-framed messages emphasizing the benefits of quitting
      seem to be preferable when working with adult patients who smoke tobacco
      products. The evidence also suggests that moderators of treatment should guide
      framed statements made to patients. Meta-analyses have provided consistent
      moderators of treatment such as need for cognition, but future studies should
      further define the specific framed interventions that would be most helpful for
      subgroups of smokers. In conclusion, instead of using loss-framed statements like
      "Smoking will harm your health by causing problems like lung and other cancers,
      heart disease, and stroke," as a general rule, physicians should use gain-framed
      statements like "Quitting smoking will benefit your health by preventing problems
      like lung and other cancers, heart disease, and stroke."

PMID- 24436473
TI  - Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors
      and overcomes drug resistance in myeloid leukemia.
AB  - PURPOSE: The SET oncoprotein, a potent inhibitor of the protein phosphatase 2A
      (PP2A), is overexpressed in leukemia. We evaluated the efficacy of SET antagonism
      in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cell lines, a
      murine leukemia model, and primary patient samples using OP449, a specific, cell
      penetrating peptide that antagonizes SET's inhibition of PP2A. EXPERIMENTAL
      DESIGN: In vitro cytotoxicity and specificity of OP449 in CML and AML cell lines
      and primary samples were measured using proliferation, apoptosis, and clonogenic
      assays. Efficacy of target inhibition by OP449 was evaluated by immunoblotting
      and PP2A assay. In vivo antitumor efficacy of OP449 was measured in human HL-60
      xenografted murine model. RESULTS: We observed that OP449 inhibited growth of CML
      cells including those from patients with blastic phase disease and patients
      harboring highly drug-resistant BCR-ABL1 mutations. Combined treatment with OP449
      and ABL1 tyrosine kinase inhibitors was significantly more cytotoxic to K562
      cells and primary CD34(+) CML cells. SET protein levels remained unchanged with
      OP449 treatment, but BCR-ABL1-mediated downstream signaling was significantly
      inhibited with the degradation of key signaling molecules such as BCR-ABL1,
      STAT5, and AKT. Similarly, AML cell lines and primary patient samples with
      various genetic lesions showed inhibition of cell growth after treatment with
      OP449 alone or in combination with respective kinase inhibitors. Finally, OP449
      reduced the tumor burden of mice xenografted with human leukemia cells.
      CONCLUSIONS: We demonstrate a novel therapeutic paradigm of SET antagonism using
      OP449 in combination with tyrosine kinase inhibitors for the treatment of CML and
      AML.

PMID- 24436475
TI  - Low nonfasting triglycerides and reduced all-cause mortality: a mendelian
      randomization study.
AB  - BACKGROUND: Increased nonfasting plasma triglycerides marking increased amounts
      of cholesterol in remnant lipoproteins are important risk factors for
      cardiovascular disease, but whether lifelong reduced concentrations of
      triglycerides on a genetic basis ultimately lead to reduced all-cause mortality
      is unknown. We tested this hypothesis. METHODS: Using individuals from the
      Copenhagen City Heart Study in a mendelian randomization design, we first tested
      whether low concentrations of nonfasting triglycerides were associated with
      reduced all-cause mortality in observational analyses (n = 13 957); second,
      whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase,
      resulting in reduced nonfasting triglycerides and remnant cholesterol, were
      associated with reduced all-cause mortality (n = 10 208). RESULTS: During a
      median 24 and 17 years of 100% complete follow-up, 9991 and 4005 individuals died
      in observational and genetic analyses, respectively. In observational analyses
      compared to individuals with nonfasting plasma triglycerides of 266-442 mg/dL
      (3.00-4.99 mmol/L), multivariably adjusted hazard ratios for all-cause mortality
      were 0.89 (95% CI 0.78-1.02) for 177-265 mg/dL (2.00-2.99 mmol/L), 0.74 (0.65
      0.84) for 89-176 mg/dL (1.00-1.99 mmol/L), and 0.59 (0.51-0.68) for individuals
      with nonfasting triglycerides <89 mg/dL (<1.00 mmol/L). The odds ratio for a
      genetically derived 89-mg/dL (1-mmol/L) lower concentration in nonfasting
      triglycerides was 0.50 (0.30-0.82), with a corresponding observational hazard
      ratio of 0.87 (0.85-0.89). Also, the odds ratio for a genetically derived 50%
      lower concentration in nonfasting triglycerides was 0.43 (0.23-0.80), with a
      corresponding observational hazard ratio of 0.73 (0.70-0.77). CONCLUSIONS:
      Genetically reduced concentrations of nonfasting plasma triglycerides are
      associated with reduced all-cause mortality, likely through reduced amounts of
      cholesterol in remnant lipoproteins.

PMID- 24436476
TI  - Magnetically promoted rapid immunoreactions using functionalized fluorescent
      magnetic beads: a proof of principle.
AB  - BACKGROUND: Accurate detection and monitoring of disease-related biomarkers is
      important in understanding pathophysiology. We devised a rapid immunoreaction
      system that uses submicrometer polymer-coated fluorescent ferrite (FF) beads
      containing both ferrites (magnetic iron oxide) and fluorescent europium
      complexes. METHODS: FF beads were prepared by encapsulation of hydrophobic
      europium complexes into the polymer layers of affinity magnetic beads using
      organic solvent. A sandwich immunoassay using magnetic collection of antibody
      coated FF beads to a specific place was performed. Brain natriuretic peptide and
      prostate-specific antigen were selected as target detection antigens to
      demonstrate the feasibility of this approach. An immunohistochemical staining
      using magnetic collection of antibody-coated FF beads onto carcinoma cell samples
      was also performed. RESULTS: The sandwich immunoassays, taking advantage of the
      magnetic collection of antibody-coated FF beads, detected target antigens within
      5 min of sample addition. Without magnetic collection, the sandwich immunoassay
      using antibody-coated FF beads required long times, similar to conventional
      immunoassays. Using the magnetic collection of antibody-coated FF beads,
      immunohistochemical staining enabled discrimination of carcinoma cells within 20
      min. CONCLUSIONS: This proof of principle system demonstrates that
      immunoreactions involving the magnetic collection of antibody-coated FF beads
      allow acceleration of the antigen-antibody reaction. The simple magnetic
      collection of antibody-coated FF beads to a specific space enables rapid
      detection of disease-related biomarkers and identification of carcinoma cells.

PMID- 24436477
TI  - Provider and care characteristics associated with timing of dialysis initiation.
AB  - BACKGROUND AND OBJECTIVES: There is a trend in the United States to maintenance
      dialysis initiation at higher levels of estimated GFR. This study aimed to
      determine whether provider characteristics and pre-ESRD nephrology care and
      vascular access are independently associated with higher estimated GFR at
      initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective
      cohort study used US Renal Data System data for patients who initiated dialysis
      in 2006 (n=83,621) and American Medical Association Physician Master File data
      for provider characteristics. Patient characteristics and estimated GFR were
      defined, and providers at dialysis initiation were identified. Earlier dialysis
      initiation was defined as initiation at estimated GFR>10 ml/min per 1.73 m(2).
      Nephrologist density per 100 ESRD patients was calculated by Health Service Area
      in 2006. Associations between provider characteristics and estimated GFR were
      determined using logistic regression and linear regression models, accounting for
      provider clustering. RESULTS: Of the cohort, 47.8% of patients initiated dialysis
      at estimated GFR>10 ml/min per 1.73 m(2), and 16.2% of patients initiated
      dialysis at estimated GFR>=15 ml/min per 1.73 m(2). Predialysis nephrologist care
      for 0-12 months was associated with greater odds of earlier initiation compared
      with no care. Patients initiating with an arteriovenous fistula or graft were
      more likely to initiate earlier than patients initiating with a catheter.
      Provider sex was not associated with timing of dialysis initiation as measured by
      estimated GFR. Care by providers who graduated from nondomestic medical schools
      was associated with greater odds of earlier initiation. Greater provider
      experience was associated with lower likelihood of earlier initiation.
      CONCLUSION: This study supports the hypothesis that provider factors are
      associated with timing of dialysis initiation in the United States.

PMID- 24436478
TI  - Clinical correlates of insulin sensitivity and its association with mortality
      among men with CKD stages 3 and 4.
AB  - BACKGROUND AND OBJECTIVES: Insulin resistance participates in the pathogenesis of
      multiple metabolic and cardiovascular diseases. CKD patients have impaired
      insulin sensitivity, but the clinical correlates and outcome associations of
      impaired insulin sensitivity in this vulnerable population are not well defined.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prospective cohort study was
      from the third examination cycle of the Uppsala Longitudinal Study of Adult Men,
      a population-based survey of elderly men ages 70-71 years; insulin sensitivity
      was assessed by glucose disposal rate as measured with euglycemic clamps.
      Inclusion criterion was eGFR<60 ml/min per 1.73 m(2) (n=543). Exclusion criteria
      were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men
      with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m(2); range=20.2-59.5
      ml/min per 1.73 m(2)). RESULTS: The mean of glucose disposal rate was 5.4 +/- 1.9
      mg/kg per minute. In multivariable analysis, the independent clinical correlates
      of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to
      0.04), hypertension (-0.48; 95% confidence interval, -0.86 to -0.11),
      hyperlipidemia (-0.51; 95% confidence interval, -0.84 to -0.18), and body mass
      index (-0.32; 95% confidence interval, -0.37 to -0.27). During follow-up
      (median=10.0 years; interquartile range=8.7-11.0 years), 149 participants died.
      In Cox regression models, glucose disposal rate was not associated with all-cause
      or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed
      between glucose disposal rate and physical activity or smoking in total mortality
      association. After subsequent stratification, glucose disposal rate was an
      independent correlate of all-cause mortality in smokers (adjusted hazard ratio,
      0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose
      disposal rate increase) and physically inactive individuals (hazard ratio, 0.77;
      95% confidence interval, 0.61 to 0.97) but not their counterparts. CONCLUSION:
      eGFR, together with various components of the metabolic syndrome, contributed to
      explain the variance of insulin sensitivity in men with CKD stages 3 and 4.
      Insulin sensitivity was associated with a lower mortality risk in individuals who
      smoked and individuals who were physically inactive.

PMID- 24436479
TI  - Early dialysis initiation, a look from the rearview mirror to what's ahead.

PMID- 24436480
TI  - Topical steroid for chronic rhinosinusitis without polyps.
AB  - The "Cochrane Corner" is a quarterly section in the Journal that highlights
      systematic reviews relevant to otolaryngology-head and neck surgery, with invited
      commentary to aid clinical decision making. This installment features a Cochrane
      Review, titled "Topical Steroid for Chronic Rhinosinusitis without Polyps," that
      finds good evidence to support therapeutic benefits with no increase in adverse
      events compared with placebo controls. 

PMID- 24436481
TI  - Otolaryngology-head and neck surgery physician work force issues: an analysis for
      future specialty planning.
AB  - OBJECTIVE: To predict future trends in the otolaryngology workforce and propose
      solutions to correct the identified discrepancies between supply and demand.
      STUDY DESIGN: Economic modeling and analysis. SETTING: Data sets at national
      medical and economic organizations. SUBJECTS AND METHODS: Based on current
      American Academy of Otolaryngology-Head and Neck Surgery, American Medical
      Association, and National Residency Matching Program data sets, population census
      data, and historical physician growth demand curves, the future otolaryngology
      workforce supply and demand were modeled. Adjustments were made for projected
      increases in mid-level providers, increased insurance coverage, and the potential
      effects of lifestyle preferences. RESULTS: There are currently approximately 8600
      otolaryngologists in the United States. Estimated demand by 2025 is 11,127 based
      on projected population growth and anticipated increase in insurance coverage.
      With an average retirement age of 65 years and no increase in PGY-1 positions for
      the specialty, the number of otolaryngologists in 2025 will be approximately 2500
      short of projected demand. This shortfall will not be adequately compensated by
      mid-level providers performing less intensive services and may be increased by
      lifestyle preferences and changing demographics among medical students and
      residents. The current geographic maldistribution of otolaryngologists is likely
      to be exacerbated. CONCLUSION: The specialty needs to actively plan for the
      coming otolaryngologist shortage and train mid-level providers within the
      specialty. Failure to plan appropriately may result in a reduction in scope of
      practice of high-intensity services, which will likely remain a physician
      prerogative. Given the limited likelihood of a significant increase in residency
      slots, strong consideration should be given to shortening the base otolaryngology
      training program length.

PMID- 24436482
TI  - Commentary on "Otolaryngology-head and neck surgery physician workforce issues an
      analysis for future specialty planning" by Kim, Cooper, and Kennedy.
AB  - An impending physician shortage has been projected. The article by Kim, Cooper,
      and Kennedy, titled "Otolaryngology-Head and Neck Surgery Physician Workforce
      Issues: An Analysis for Future Specialty Planning," is an attempt to evaluate and
      address this potential shortage as it applies to otolaryngology. The authors of
      this comment have concerns about the article's assumptions, design, and
      recommendations. Kim et al attempt to extrapolate data from other specialties and
      other countries to the US otolaryngology workforce, use that data in modeling
      methods without demonstrated validity, and based on their analysis, they
      recommend drastic changes to otolaryngologic training and practice in the United
      States. Particularly troublesome are (1) the emphasis placed on gender and part
      time work and (2) the measurement of productivity defined as hours worked per
      week. Before redefining our specialty, more thorough and systematic data
      acquisition and review are necessary to meet the needs of our patients now and in
      the future. 

PMID- 24436483
TI  - Analysis of the workforce and otolaryngology specialty planning.

PMID- 24436485
TI  - Re: need for bronchoscopy in adenotonsillectomy.

PMID- 24436487
TI  - Emerging trends in the management of laryngeal rhabdomyosarcoma.

PMID- 24436488
TI  - A call for systematic data collection in tinnitus patients.

PMID- 24436491
TI  - Long-term oral nutrition supplementation improves outcomes in malnourished
      patients with chronic kidney disease on hemodialysis.
AB  - BACKGROUND: There is no consensus on the type, time of initiation, or duration of
      use of enteral nutrition in patients with chronic kidney disease (CKD). This
      study aimed to compare the effects of a renal-specific oral nutrition supplement
      (RS-ONS) and a standard recommended nutrition regime on biochemical and nutrition
      markers in malnourished patients with CKD on hemodialysis. METHODS: Sixty-two
      malnourished patients with CKD, divided into experimental (RS-ONS; n = 32; mean
      [SD] age, 62.0 [11.3] years; 55.2% female) and control (CON; n = 30; mean [SD]
      age, 57.2 [12.3] years; 31% female) groups, were evaluated for anthropometric,
      biochemical, and inflammatory parameters. RESULTS: Mean (SD) serum albumin levels
      were significantly increased in the RS-ONS group from 3.5 (0.3) g/dL at baseline
      to 3.7 (0.2) g/dL at 6 months (P = .028). Significantly fewer patients had serum
      albumin levels of <3.5 g/dL after month 6. Dry weight of patients significantly
      increased in the RS-ONS but decreased in the CON groups (P < .001 for each).
      Percent change from baseline revealed negative results for bioelectrical
      impedance analysis (P < .001) in the CON group. Malnutrition inflammation score
      at 6 months (P = .006) and erythropoietin (EPO) dose requirements were higher in
      the CON group (P = .012). CONCLUSIONS: Our findings indicate that consuming RS
      ONS improves serum albumin and anthropometric measures, as well as reduces EPO
      dose, in patients with CKD.

PMID- 24436492
TI  - A miniature tension sensor to measure surgical suture tension of deformable
      musculoskeletal tissues during joint motion.
AB  - The aim of this study was to develop a new suture tension sensor for
      musculoskeletal soft tissue that shows deformation or movements. The suture
      tension sensor was 10 mm in size, which was small enough to avoid conflicting
      with the adjacent sensor. Furthermore, the sensor had good linearity up to a
      tension of 50 N, which is equivalent to the breaking strength of a size 1
      absorbable suture defined by the United States Pharmacopeia. The design and
      mechanism were analyzed using a finite element model prior to developing the
      actual sensor. Based on the analysis, adequate material was selected, and the
      output linearity was confirmed and compared with the simulated result. To
      evaluate practical application, the incision of the skin and capsule were sutured
      during simulated total knee arthroplasty. When conventional surgery and minimally
      invasive surgery were performed, suture tensions were compared. In minimally
      invasive surgery, the distal portion of the knee was dissected, and the proximal
      portion of the knee was dissected additionally in conventional surgery. In the
      skin suturing, the maximum tension was 4.4 N, and this tension was independent of
      the sensor location. In contrast, the sensor suturing the capsule in the distal
      portion had a tension of 4.4 N in minimally invasive surgery, while the proximal
      sensor had a tension of 44 N in conventional surgery. The suture tensions
      increased nonlinearly and were dependent on the knee flexion angle. Furthermore,
      the tension changes showed hysteresis. This miniature tension sensor may help
      establish the optimal suturing method with adequate tension to ensure wound
      healing and early recovery. 

PMID- 24436493
TI  - International research: comparison and collaboration to understand and promote
      palliative care.

PMID- 24436494
TI  - High efficiency protocol of DNA extraction from Micromys minutus mandibles from
      owl pellets: a tool for molecular research of cryptic mammal species.
AB  - Owl pellets have high potential as a source of DNA. However, this noninvasive
      method of collecting DNA is rarely used, and its methodological aspects are
      poorly understood. We investigated the methodology for DNA extraction and
      amplification from owl pellets containing the smallest European rodent-the
      Harvest mouse Micromys minutus-as an example. We used mandibles identified in owl
      pellets for mitochondrial and nuclear DNA amplification. For DNA extraction, we
      tested two commercial protocols and utilized a protocol being a combination of
      two commercial kits which ensured high efficiency of DNA extraction.
      Additionally, we recorded that the amount of DNA was five times higher in
      extracts from teeth as compared to DNA extracts from jawbones derived from the
      same mandible. The quantity of DNA was significantly positively correlated with
      biological sample weight; however, the age of the pellet remains had an impact on
      the level of inhibition. We recorded inhibition in 40 % of mtDNA extracts derived
      from pellets older than 150 months, whereas in DNA extracts from pellets younger
      than 80 months, we did not observe a negative impact of inhibition on PCR
      efficiency. The amplification success rate was 89.9 % for the mitochondrial
      fragment and 39.4 % in the case of the nuclear fragment. We observed partial
      degradation of DNA evidenced by the fact that the longest fragments that we were
      able to amplify in the case of mtDNA were 450 and 200 bp for nuDNA. The study
      shows that pellets can be considered as a source of DNA and have high potential
      for molecular research in the case of threatened species and species that are
      difficult to study using standard field techniques.

PMID- 24436495
TI  - Competing for space: female chimpanzees are more aggressive inside than outside
      their core areas.
AB  - Female space use can have important fitness consequences, which are likely due to
      differential access to food resources. Many studies have explored spatial
      competition in solitary species, but little is known about how individuals in
      social species compete over shared space. In this study, we investigate spatial
      patterns of aggression among female East African chimpanzees, Pan troglodytes
      schweinfurthii. This species provides an excellent opportunity to study spatial
      competition since (1) female chimpanzees occupy overlapping core areas (small
      areas of the community range in which individuals concentrate their space use)
      and (2) female core area quality is correlated with reproductive success,
      suggesting that females compete over long-term access to core areas. Here, we
      examine how female aggression towards other females varies inside and outside
      individual female core areas during a 14-year period at Gombe National Park,
      Tanzania. Overall, females showed higher rates of aggression inside than outside
      their own core areas. This pattern was driven by spatial variation in aggression
      in nonfeeding contexts. While food-related aggression did not vary spatially,
      females were more aggressive in nonfeeding contexts inside their core areas than
      they were outside their core areas. These results suggest that female chimpanzees
      follow a mixed strategy in which they compete for long-term access to resources
      in their core areas as well as for immediate access to food throughout the
      community range.

PMID- 24436496
TI  - p-Hydroxyphenacyl photoremovable protecting groups - Robust photochemistry
      despite substituent diversity.
AB  - A broadly based investigation of the effects of a diverse array of substituents
      on the photochemical rearrangement of p-hydroxyphenacyl esters has demonstrated
      that common substituents such as F, MeO, CN, CO2R, CONH2, and CH3 have little
      effect on the rate and quantum efficiencies for the photo-Favorskii rearrangement
      and the release of the acid leaving group or on the lifetimes of the reactive
      triplet state. A decrease in the quantum yields across all substituents was
      observed for the release and rearrangement when the photolyses were carried out
      in buffered aqueous media at pHs that exceeded the ground-state pKa of the
      chromophore where the conjugate base is the predominant form. Otherwise,
      substituents have only a very modest effect on the photoreaction of these robust
      chromophores.

PMID- 24436497
TI  - New Theoretical Results on Channelized Hotelling Observer Performance Estimation
      with Known Difference of Class Means.
AB  - Task-based assessments of image quality constitute a rigorous, principled
      approach to the evaluation of imaging system performance. To conduct such
      assessments, it has been recognized that mathematical model observers are very
      useful, particularly for purposes of imaging system development and optimization.
      One type of model observer that has been widely applied in the medical imaging
      community is the channelized Hotelling observer (CHO). Since estimates of CHO
      performance typically include statistical variability, it is important to control
      and limit this variability to maximize the statistical power of image-quality
      studies. In a previous paper, we demonstrated that by including prior knowledge
      of the image class means, a large decrease in the bias and variance of CHO
      performance estimates can be realized. The purpose of the present work is to
      present refinements and extensions of the estimation theory given in our previous
      paper, which was limited to point estimation with equal numbers of images from
      each class. Specifically, we present and characterize minimum-variance unbiased
      point estimators for observer signal-to-noise ratio (SNR) that allow for unequal
      numbers of lesion-absent and lesion-present images. Building on this SNR point
      estimation theory, we then show that confidence intervals with exactly-known
      coverage probabilities can be constructed for commonly-used CHO performance
      measures. Moreover, we propose simple, approximate confidence intervals for CHO
      performance, and we show that they are well-behaved in most scenarios of
      interest.

PMID- 24436498
TI  - Relieving the Time Squeeze? Effects of a White-Collar Workplace Change on
      Parents.
AB  - Employed parents perceive a time squeeze even as trends from the 1960s show they
      are spending more time with their children. Work conditions (e.g., hours and
      schedule control) would seem to affect both parents' time with children and
      perceived time squeeze, but most studies rely on cross-sectional data that do not
      establish causality. The authors examined the effects of the introduction of a
      workplace flexibility initiative (Results Only Work Environment [ROWE]) on
      changes in mothers' and fathers' perceptions of the adequacy of their time with
      children and actual time spent with children (N = 225). Baseline data show the
      importance of work conditions for parents' sense of perceived time adequacy.
      Panel data show that mothers (but not fathers) in ROWE report increased schedule
      control and improved time adequacy, but no change in actual time spent with
      children, except that ROWE increases evening meals with children for mothers
      sharing few meals at baseline.

PMID- 24436499
TI  - Books and Literature.

PMID- 24436500
TI  - A SIEVE M-THEOREM FOR BUNDLED PARAMETERS IN SEMIPARAMETRIC MODELS, WITH
      APPLICATION TO THE EFFICIENT ESTIMATION IN A LINEAR MODEL FOR CENSORED DATA.
AB  - In many semiparametric models that are parameterized by two types of parameters -
      a Euclidean parameter of interest and an infinite-dimensional nuisance parameter,
      the two parameters are bundled together, i.e., the nuisance parameter is an
      unknown function that contains the parameter of interest as part of its argument.
      For example, in a linear regression model for censored survival data, the
      unspecified error distribution function involves the regression coefficients.
      Motivated by developing an efficient estimating method for the regression
      parameters, we propose a general sieve M-theorem for bundled parameters and apply
      the theorem to deriving the asymptotic theory for the sieve maximum likelihood
      estimation in the linear regression model for censored survival data. The
      numerical implementation of the proposed estimating method can be achieved
      through the conventional gradient-based search algorithms such as the Newton
      Raphson algorithm. We show that the proposed estimator is consistent and
      asymptotically normal and achieves the semiparametric efficiency bound.
      Simulation studies demonstrate that the proposed method performs well in
      practical settings and yields more efficient estimates than existing estimating
      equation based methods. Illustration with a real data example is also provided.

PMID- 24436501
TI  - Land Use Change on Household Farms in the Ecuadorian Amazon: Design and
      Implementation of an Agent-Based Model.
AB  - This paper describes the design and implementation of an Agent-Based Model (ABM)
      used to simulate land use change on household farms in the Northern Ecuadorian
      Amazon (NEA). The ABM simulates decision-making processes at the household level
      that is examined through a longitudinal, socio-economic and demographic survey
      that was conducted in 1990 and 1999. Geographic Information Systems (GIS) are
      used to establish spatial relationships between farms and their environment,
      while classified Landsat Thematic Mapper (TM) imagery is used to set initial land
      use/land cover conditions for the spatial simulation, assess from-to land
      use/land cover change patterns, and describe trajectories of land use change at
      the farm and landscape levels. Results from prior studies in the NEA provide
      insights into the key social and ecological variables, describe human behavioral
      functions, and examine population-environment interactions that are linked to
      deforestation and agricultural extensification, population migration, and
      demographic change. Within the architecture of the model, agents are classified
      as active or passive. The model comprises four modules, i.e., initialization,
      demography, agriculture, and migration that operate individually, but are linked
      through key household processes. The main outputs of the model include a
      spatially-explicit representation of the land use/land cover on survey and non
      survey farms and at the landscape level for each annual time-step, as well as
      simulated socio-economic and demographic characteristics of households and
      communities. The work describes the design and implementation of the model and
      how population-environment interactions can be addressed in a frontier setting.
      The paper contributes to land change science by examining important pattern
      process relations, advocating a spatial modeling approach that is capable of
      synthesizing fundamental relationships at the farm level, and links people and
      environment in complex ways.

PMID- 24436502
TI  - Regional Issue: Social Policy Developments in Australia and New Zealand.
AB  - In his celebrated work of comparative policy, Francis Castles argued that a
      radical wage-earning model of welfare had evolved in Australia and New Zealand
      over the course of the 20th century. The Castles' thesis is shown to have two
      parts: first, the 'fourth world of welfare' argument that rests upon protection
      of workers; and, second, an emphasis on the path-dependent nature of social
      policy. It is perfectly possible to accept the second premise of the argument
      without the first, and indeed many do so. It is also possible to accept the
      importance of wage level protection concerns in Australasian social policy
      without accepting the complete fourth world thesis. This article explores the
      path of social democracy in Australia and New Zealand and the continuing
      importance of labour market regulation, as well as considering the extent to
      which that emphasis still makes Australasian social policy distinctive in the
      modern age. The argument focuses on the data and policies relating to labour
      market protection and wages, as well the systems of welfare and social
      protection, and the comparative information on poverty and inequality.

PMID- 24436503
TI  - Resampling Procedures for Making Inference under Nested Case-control Studies.
AB  - The nested case-control (NCC) design have been widely adopted as a cost-effective
      solution in many large cohort studies for risk assessment with expensive markers,
      such as the emerging biologic and genetic markers. To analyze data from NCC
      studies, conditional logistic regression (Goldstein and Langholz, 1992; Borgan et
      al., 1995) and maximum likelihood (Scheike and Juul, 2004; Zeng et al., 2006)
      based methods have been proposed. However, most of these methods either cannot be
      easily extended beyond the Cox model (Cox, 1972) or require additional modeling
      assumptions. More generally applicable approaches based on inverse probability
      weighting (IPW) have been proposed as useful alternatives (Samuelsen, 1997; Chen,
      2001; Samuelsen et al., 2007). However, due to the complex correlation structure
      induced by repeated finite risk set sampling, interval estimation for such IPW
      estimators remain challenging especially when the estimation involves non-smooth
      objective functions or when making simultaneous inferences about functions.
      Standard resampling procedures such as the bootstrap cannot accommodate the
      correlation and thus are not directly applicable. In this paper, we propose a
      resampling procedure that can provide valid estimates for the distribution of a
      broad class of IPW estimators. Simulation results suggest that the proposed
      procedures perform well in settings when analytical variance estimator is
      infeasible to derive or gives less optimal performance. The new procedures are
      illustrated with data from the Framingham Offspring Study to characterize
      individual level cardiovascular risks over time based on the Framingham risk
      score, C-reactive protein (CRP) and a genetic risk score.

PMID- 24436504
TI  - Exploratory time varying lagged regression: modeling association of cognitive and
      functional trajectories with expected clinic visits in older adults.
AB  - Motivated by a longitudinal study on factors affecting the frequency of clinic
      visits of older adults, an exploratory time varying lagged regression analysis is
      proposed to relate a longitudinal response to multiple cross-sectional and
      longitudinal predictors from time varying lags. Regression relations are allowed
      to vary with time through smooth varying coefficient functions. The main goal of
      the proposal is to detect deviations from a concurrent varying coefficient model
      potentially in a subset of the longitudinal predictors with nonzero estimated
      lags. The proposed methodology is geared towards irregular and infrequent data
      where different longitudinal variables may be observed at different frequencies,
      possibly at unsynchronized time points and contaminated with additive measurement
      error. Furthermore, to cope with the curse of dimensionality which limits related
      current modeling approaches, a sequential model building procedure is proposed to
      explore and select the time varying lags of the longitudinal predictors. The
      estimation procedure is based on estimation of the moments of the predictor and
      response trajectories by pooling information from all subjects. The finite sample
      properties of the proposed estimation algorithm are studied under various lag
      structures and correlation levels among the predictor processes in simulation
      studies. Application to the clinic visits data show the effect of cognitive and
      functional impairment scores from varying lags on the frequency of the clinic
      visits throughout the study.

PMID- 24436505
TI  - The Moderating Effect of Substance Abuse Service Accessibility on the
      Relationship between Child Maltreatment and Neighborhood Alcohol Availability.
AB  - This study investigates how the relationship between dense concentrations of
      alcohol retailers and high rates of child maltreatment may be moderated by the
      presence of substance abuse service facilities. Using a cross-sectional design,
      the study utilized data from Bergen County, New Jersey on child maltreatment
      reports, alcohol-selling retailers, substance abuse service facilities, and the
      United States Census. Findings indicate child maltreatment rates were higher in
      neighborhoods with lower socioeconomic status and those with greater alcohol
      outlet density. Neighborhoods with easily accessed substance abuse service
      facilities had lower rates of child maltreatment. Additionally, the relationship
      between child maltreatment and alcohol outlet density was moderated by the
      presence of substance abuse service facilities. The study findings highlight the
      relevance of making primary prevention approaches readily available and using
      multi-sector collaboration to reduce child maltreatment.

PMID- 24436506
TI  - Category labels induce boundary-dependent perceptual warping in learned speech
      categories.
AB  - Adults tend to perceive speech sounds from their native language as members of
      distinct and stable categories; however, they fail to perceive differences
      between many non-native speech sounds without a great deal of training. The
      present study investigates the effects of categorization training on adults'
      ability to discriminate non-native phonetic contrasts. It was hypothesized that
      only individuals who successfully learned the appropriate categories would show
      selective improvements in discriminating between-category contrasts. Participants
      were trained to categorize progressively narrow phonetic contrasts across one of
      two non-native boundaries, with discrimination pre- and post-tests completed to
      measure the effects of training on participants' perceptual sensitivity. Results
      suggest that changes in adults' ability to discriminate a non-native contrast
      depend on their successful learning of the relevant category structure.
      Furthermore, post-training identification functions show that changes in
      perceptual categories specifically correspond to their relative placement of the
      category boundary. Taken together, these results indicate that learning to assign
      category labels to a non-native speech continuum is sufficient to induce
      discontinuous perception of between- versus within-category contrasts.

PMID- 24436507
TI  - Minimizing Concentration Effects in Water-Based, Laminar-Flow Condensation
      Particle Counters.
AB  - Concentration effects in water condensation systems, such as used in the water
      based condensation particle counter, are explored through numeric modeling and
      direct measurements. Modeling shows that the condensation heat release and vapor
      depletion associated with particle activation and growth lowers the peak
      supersaturation. At higher number concentrations, the diameter of the droplets
      formed is smaller, and the threshold particle size for activation is higher. This
      occurs in both cylindrical and parallel plate geometries. For water-based systems
      we find that condensational heat release is more important than is vapor
      depletion. We also find that concentration effects can be minimized through use
      of smaller tube diameters, or more closely spaced parallel plates. Experimental
      measurements of droplet diameter confirm modeling results.

PMID- 24436508
TI  - How a songbird with a continuous singing style modulates its song when
      territorially challenged.
AB  - In songbirds of the temperate zone, often only males sing and their songs serve
      to attract females and to deter territorial rivals. In many species, males vary
      certain aspects of their singing behavior when engaged in territorial
      interactions. Such variation may be an honest signal of the traits of the
      signaler, such as fighting strength, condition, or aggressive motivation, and may
      be used by receivers in decisions on whether to retreat or to escalate a fight.
      This has been studied intensively in species that sing discontinuously, in which
      songs are alternating with silent pauses. We studied contextual variation in the
      song of skylarks (Alauda arvensis), a songbird with a large vocal repertoire and
      a continuous and versatile singing style. We exposed subjects to simulated
      territorial intrusions by broadcasting conspecific song and recorded their vocal
      responses. We found that males sing differently if they are singing spontaneously
      with no other conspecific around than if they are territorially challenged. In
      this last case, males produced lower-frequency syllables. Furthermore, they
      increased the sound density of their song: they increased the proportion of sound
      within song. They seem to do so by singing different elements of their repertoire
      when singing reactively. Furthermore, they increased the consistency of mean peak
      frequency: they repeated syllable types with less variability when singing
      reactively. Such contextual variation suggests that skylarks might use low
      frequencies, sound density, and song consistency to indicate their competitive
      potential, and thus, those song features might be important for mutual assessment
      of competitive abilities.

PMID- 24436509
TI  - Mortality in South Africa - socioeconomic profile and association with self
      reported health.
AB  - This paper exploits the first two waves of NIDS to describe the socioeconomic
      profile of mortality and to assess whether self-rated health status is predictive
      of mortality between waves. Mortality rates in NIDS are in line with estimates
      from official death notification data and display the expected hump of excess
      mortality in early and middle adulthood due to AIDS, with the excess peaking
      earlier for women than for men. We find evidence of a socioeconomic gradient in
      mortality with higher rates of mortality for individuals from asset poor
      households and with lower levels of education. Consistent with evidence from many
      industrialized countries and a few developing countries, we find self-rated
      health to be a significant predictor of two year mortality, an association that
      remains after controlling for socioeconomic status and several other subjective
      and objective measures of health.

PMID- 24436511
TI  - Seeking balance, professional and otherwise.

PMID- 24436510
TI  - Cell-based therapies for regenerating bone.
AB  - Cellular therapies to replenish bone lost due to acquired conditions such as
      trauma, infection, tumor, periprosthetic osteolysis and other etiologies have
      become widespread. Traditional, open, surgical bone grafting techniques have
      given way to newer cellular therapies that are potentially less invasive and have
      a lower complication rate and faster recovery time. These new technologies
      include bone marrow harvesting with concentration of osteoprogenitor cells
      with/without cell culture, scaffolds which are both osteoconductive and
      osteoinductive, attempts to facilitate mesenchymal stem cell and osteoprogenitor
      cell homing both locally and systemically, genetic engineering of specialized
      stem cells, and the use of potentially immune-privileged fetal and other types of
      stem cells. Some of these techniques have already been introduced into the
      orthopaedic clinic, whereas others are still in the pre-clinical testing phase.
      Given the limited supply of autologous graft, these new techniques will have a
      dramatic impact on bone regeneration in the future.

PMID- 24436512
TI  - Chemoembolization of hepatocellular carcinoma.
AB  - Transarterial chemoembolization (TACE) is the current standard of care for
      patients with intermediate-stage hepatocellular carcinoma (HCC) and relatively
      preserved liver function. In a meta-analysis of randomized controlled trials
      comparing conventional TACE regimens-including the administration of an
      anticancer-in-oil emulsion followed by embolic agents-versus best supportive
      care, TACE was shown to improve median survival from 16 to 20 months. Various
      strategies to improve outcomes for this patient group have become the subject of
      much ongoing clinical research. The introduction of an embolic drug-eluting bead
      (DEB) has been shown to substantially improve the pharmacokinetic profile of
      TACE, providing levels of consistency and repeatability not available with
      conventional regimens while concomitantly significantly diminishing systemic drug
      exposure. In randomized trials, DEB-TACE significantly reduced liver toxicity and
      drug-related adverse events compared with conventional TACE. In this article,
      technique, indications and contraindications, and clinical outcomes of
      conventional and DEB-TACE in the management of HCC are reviewed. In addition,
      scientific background and early clinical experience with the use of combination
      regimens including TACE and systemically active molecular-targeted agents with
      antiangiogenic properties are discussed. The combination of DEB-TACE and
      antiangiogenic therapy represents a potentially powerful approach that is
      currently undergoing clinical investigation in a phase 3 setting. 

PMID- 24436513
TI  - Intra-arterial therapies for metastatic colorectal cancer.
AB  - Intra-arterial therapies for unresectable hepatic metastases from colorectal
      cancer include radioembolization (RE) with yttrium-90 microspheres, transarterial
      chemoembolization (TACE), hepatic arterial infusion, and percutaneous hepatic
      perfusion using an organ isolation system. In this article, we discuss our
      approach toward treatment selection, followed by details of how RE and TACE are
      performed at our institution. 

PMID- 24436514
TI  - Transarterial therapies for the treatment of intrahepatic cholangiocarcinoma.
AB  - Cholangiocarcinoma, whether arising from the intrahepatic or extrahepatic biliary
      system, is a rare but devastating malignancy. Prognosis is poor, with 5-year
      overall survival <5% including patients undergoing surgery. Resection is the only
      curative treatment; however, only ~30% of patients present at a resectable stage,
      and intrahepatic recurrence is common even after complete resection. This article
      discusses the current role of transarterial therapies in the treatment of
      intrahepatic cholangiocarcinoma. 

PMID- 24436515
TI  - Intra-arterial liver-directed therapies for neuroendocrine hepatic metastases.
AB  - Hepatic metastases, which are frequently seen in patients with neuroendocrine
      tumors (NETs), have a major adverse impact on the patient's quality of life and
      survival. Surgery is the treatment of choice for hepatic metastases but is
      possible in only a small percentage of patients. Systemic chemotherapy yields
      disappointing results. Somatostatin analogs are effective in controlling symptoms
      in many of these patients; however, the disease can become refractory to
      treatment. Transcatheter intra-arterial liver-directed therapies, such as hepatic
      artery embolization, chemoembolization, and radioembolization are frequently used
      in patients with NETs metastatic to the liver, especially in patients with
      refractory, unresectable, or recurrent disease. These treatments are effective in
      palliating the hormonal symptoms as well as achieving objective tumor responses.
      This review focuses on the technique, safety, and clinical efficacy of hepatic
      artery embolization, chemoembolization, and radioembolization in patients with
      metastatic NETs. 

PMID- 24436516
TI  - Transhepatic therapies for metastatic uveal melanoma.
AB  - Despite successful treatment of the primary tumor, uveal melanoma has a
      propensity to metastasize to the liver. Prognosis is poor due to the very
      aggressive nature of these tumors. Because systemic therapies are relatively
      ineffective and patient survival correlates to disease control in the liver,
      locoregional therapies provide a means of prolonging survival. We review various
      techniques including chemoembolization, immunoembolization, radioembolization,
      arterial fotemustine infusion, and hepatic perfusion for the treatment of liver
      metastases from uveal melanoma. 

PMID- 24436517
TI  - Radiofrequency ablation of liver tumors.
AB  - Radiofrequency ablation (RFA) is an alternative therapy for hepatocellular
      carcinoma and liver metastases when resection cannot be performed or, in the case
      of hepatocellular carcinoma, when transplant cannot be performed in a timely
      enough manner to avoid the risk of dropping off the transplant list. RFA has the
      advantage of being a relatively low-risk minimally invasive procedure used in the
      treatment of focal liver tumors. This review article discusses the current
      evidence supporting RFA of liver tumors, as well as the indications,
      complications, and follow-up algorithms used after RFA. 

PMID- 24436518
TI  - Microwave ablation of hepatic malignancy.
AB  - Microwave ablation is an extremely promising heat-based thermal ablation modality
      that has particular applicability in treating hepatic malignancies. Microwaves
      can generate very high temperatures in very short time periods, potentially
      leading to improved treatment efficiency and larger ablation zones. As the
      available technology continues to improve, microwave ablation is emerging as a
      valuable alternative to radiofrequency ablation in the treatment of hepatic
      malignancies. This article reviews the current state of microwave ablation
      including technical and clinical considerations. 

PMID- 24436519
TI  - Irreversible electroporation of hepatic malignancy.
AB  - Hepatocellular carcinoma (HCC) is a worldwide problem of epidemic proportions,
      best treated in a multidisciplinary setting. Major advances have been made in all
      specialties that manage patients with HCC, with surgical options at one end of
      the spectrum and palliative chemotherapy on the other, and the vast majority of
      patients require the involvement and expertise of interventional oncology.
      Several ablative and transarterial technologies are currently available.
      Irreversible electroporation (IRE) is a new ablative technology that uses high
      voltage, low-energy DC current to create nanopores in the cell membrane,
      disrupting the homeostasis mechanism and inducing cell death by initiating
      apoptosis. This article discusses the evolution of IRE as well as its safety and
      efficacy in the context of other ablative therapies in the treatment of hepatic
      malignancies. 

PMID- 24436521
TI  - Preservation of Internal Iliac Arterial Flow during Endovascular Aortic Aneurysm
      Repair Using the "Sandwich" Technique.

PMID- 24436520
TI  - Combining locoregional therapies in the treatment of hepatocellular carcinoma.
AB  - In an effort to promote more durable local control of larger lesions, thermal
      ablation has been combined with chemical ablative techniques and with vaso
      occlusive procedures such as chemoembolization and bland embolization in an
      effort to mitigate the limitations inherent in the use of any single treatment
      for hepatocellular carcinoma (HCC) >3 cm. The heat-sink effect is the underlying
      principle for combining vaso-occlusive therapies with ablative techniques.
      Combination therapies do present viable options for abrogating tumor progression
      and potentially downsizing tumors to facilitate transplant. We discuss the two
      most commonly used combination locoregional therapies by the interventionalist
      and the evidence defining the best techniques in practice. 

PMID- 24436522
TI  - Management of transcecal renal transplant nephrostomy.

PMID- 24436523
TI  - Are We IOs or IRs?

PMID- 24436524
TI  - Epidemiology of lung cancer.
AB  - Incidence and mortality attributed to lung cancer has risen steadily since the
      1930s. Efforts to improve outcomes have not only led to a greater understanding
      of the etiology of lung cancer, but also the histologic and molecular
      characteristics of individual lung tumors. This article describes this evolution
      by discussing the extent of the current lung cancer epidemic including
      contemporary incidence and mortality trends, the risk factors for development of
      lung cancer, and details of promising molecular targets for treatment. 

PMID- 24436525
TI  - Lung cancer staging: clinical and radiologic perspectives.
AB  - Published in 2009, the 7th edition of the American Joint Committee on Cancer TNM
      staging system is the culmination of an extensive worldwide initiative to
      standardize and validate lung cancer staging. Unlike prior editions, the new
      staging system is now inclusive of small cell carcinoma and carcinoid tumors. In
      addition, significant changes were made to the T and M descriptors, resulting in
      improved prognostic stratification of disease. This review article highlights
      these changes, the rationale for their inclusion in the new staging manual, and
      the role of the radiologist in determining stage. 

PMID- 24436526
TI  - Lung cancer screening.
AB  - Lung cancer is the leading cause of cancer death. Although smoking prevention and
      cessation programs have decreased lung cancer mortality, there remains a large at
      risk population. Dismal long-term survival rates persist despite improvements in
      diagnosis, staging, and treatment. Early efforts to identify an effective
      screening test have been unsuccessful. Recent advances in multidetector computed
      tomography have allowed screening studies using low-dose computed tomography
      (LDCT) to be performed. This set the stage for the National Lung Screening Trial
      that found that annual LDCT screening benefits individuals at high risk for lung
      cancer. An understanding of the harmful effects of lung cancer screening is
      required to help maximize the benefits and decrease the risks of a lung cancer
      screening program. Although many questions remain regarding LDCT screening, a
      comprehensive lung cancer screening program of high-risk individuals will
      increase detection of preclinical and potentially curable disease, creating a new
      model of lung cancer surveillance and management. 

PMID- 24436527
TI  - Percutaneous lung biopsy: technique, efficacy, and complications.
AB  - Computed tomography-guided percutaneous needle biopsy of the lung is an
      indispensable tool in the evaluation of pulmonary abnormalities due to its high
      diagnostic accuracy in the detection of malignancy. Percutaneous biopsy in the
      lung plays a critical role in obtaining pathologic proof of malignancy, guiding
      staging and planning treatment. This article reviews biopsy techniques and their
      related efficacy and complications. 

PMID- 24436528
TI  - Electromagnetic navigational bronchoscopy.
AB  - Despite advances in technology and treatment options, lung cancer remains a
      deadly disease. National screening programs are being instituted in an attempt to
      discover lung cancer in high-risk individuals at an earlier stage. Such screening
      programs invariably discover small peripheral nodules that previously would not
      have been clinically apparent; the management of such lesions can be challenging.
      Current diagnostic options such as percutaneous biopsy are effective; however,
      they are hindered by their risk of morbidity such as pneumothorax.
      Electromagnetic bronchoscopy (ENB) is an emerging technology that allows the
      practitioner the ability to both sample and treat small peripheral pulmonary
      lesions. In experienced centers, ENB provides high rates of diagnostic yield for
      small lesions and a complication rate significantly lower than that of more
      conventional diagnostic modalities. Although there are current barriers to its
      widespread utilization (cost, specialized imaging, technical training), these
      obstacles will handled similarly to any other emerging technology and will likely
      not be long-term impediments to its use. 

PMID- 24436529
TI  - Surgical management of lung cancer.
AB  - Surgery serves an important role in the diagnosis, staging, and definitive
      management of non-small cell lung cancer (NSCLC). Resection is the primary mode
      of treatment for stage I and II NSCLC and an important component of the
      multimodality approach to stage IIIA disease. Standard resections include removal
      of the lobe involved with tumor and systematic evaluation of ipsilateral hilar
      and mediastinal lymph nodes. For early stage disease the evolving surgical
      treatment goals are aimed at decreasing morbidity and mortality through less
      invasive approaches including video-assisted thoracoscopic surgery and robotic
      approaches, and potentially decreasing the volume of lung removed for select
      patients with well-staged small peripheral tumors. For patients with locally
      advanced disease, ongoing research is focused on appropriately identifying
      patients who will most benefit from the addition of surgery to a multimodality
      regime and safely integrating resection with chemotherapy and radiotherapy. 

PMID- 24436530
TI  - Lung cancer ablation: technologies and techniques.
AB  - The incidence of lung cancers in 2012 is estimated to reach 226,160 new cases,
      with only a third of patients suitable surgical candidates. Tumor ablation has
      emerged as an important and efficacious treatment option for nonsurgical lung
      cancer patients. This localized minimally invasive therapy is best suited for
      small oligonodular lesions or favorably located metastatic tumors. Radiofrequency
      ablation has been in use for over a decade, and newer modalities including
      microwave ablation, cryoablation, and irreversible electroporation have emerged
      as additional treatment options for patients. Ablation therapies can offer
      patients and clinicians a repeatable and effective therapy for palliation and, in
      some cases, cure of thoracic malignancies. This article discusses the available
      technologies and techniques available for tumor ablation of thoracic malignancies
      including patient selection, basic aspects of procedure technique, imaging follow
      up, treatment outcomes, and comparisons between various therapies. 

PMID- 24436531
TI  - Lung cancer ablation: what is the evidence?
AB  - Percutaneous ablation of small non-small cell lung cancer (NSCLC) has been
      demonstrated to be both feasible and safe in nonsurgical candidates.
      Radiofrequency ablation (RFA), the most commonly used technique for ablation, has
      a reported rate of complete ablation of ~90%, with best results obtained in
      tumors <2 to 3 cm in diameter. The best reported 1-, 3-, and 5-year overall
      survival rates after RFA of NSCLC are 97.7%, 72.9%, and 55.7%, respectively. It
      is noteworthy that in most studies, cancer-specific survival is greater than
      overall survival due to severe comorbidities in patients treated with RFA for
      NSCLC. Aside from tumor size and tumor stage, these comorbidities are predictive
      of survival. Other ablation techniques such as microwave and irreversible
      electroporation may in the future prove to overcome some of the limitations of
      RFA, namely for large tumors or tumors close to large vessels. Stereotactic body
      radiation therapy has also been demonstrated to be highly efficacious in treating
      small lung tumors and will need to be compared with percutaneous ablation. This
      article reviews the current evidence regarding RFA for lung cancer. 

PMID- 24436532
TI  - Imaging Features following Thermal Ablation of Lung Malignancies.
AB  - Percutaneous image-guided thermal ablation is gaining attraction as an effective
      alternative to surgical resection for patients with primary and secondary
      malignancies of the lung. Currently, no standard follow-up imaging protocol has
      been established or uniformly accepted. The early identification of residual or
      recurrent tumor would in theory enable the practitioner to offer expeditious
      retreatment or alternative treatment. This review elaborates on the imaging
      findings following thermal ablation, both heat- and cold-based, of nonresectable
      pulmonary malignancies. 

PMID- 24436533
TI  - Lung cancer ablation: complications.
AB  - Although radiofrequency ablation for lung cancer is generally safe (with a
      mortality rate <1%), it may cause various complications. Common complications
      include pneumothorax, pleural effusion, and parenchymal hemorrhage. Although most
      complications can be treated conservatively or with minimal therapy, physicians
      should be aware of rare but serious complications. Potentially fatal
      complications include massive hemorrhage, intractable pneumothorax due to
      bronchopleural fistula, pulmonary artery pseudoaneurysm, systemic air embolism,
      and pneumonitis. Other serious complications include injury to the nearby tissues
      (e.g., brachial nerve plexus, phrenic nerve, diaphragm, and chest wall), needle
      tract seeding, lung abscess, empyema, and skin burn. Although cavitation of the
      ablation zone is usually insignificant clinically, such a cavity occasionally
      ruptures, leading to pneumothorax and bleeding. Cavities may also serve as a
      scaffold for fungal colonization. Precautions to minimize risk should be taken
      whenever possible. Nevertheless, serious complications may occur, and thus
      physicians should be aware of the appropriate treatments for these complications.
      This article reviews complications associated with lung cancer ablation. 

PMID- 24436534
TI  - Regional chemotherapy of the lung: transpulmonary chemoembolization in malignant
      lung tumors.
AB  - Standard treatment options in patients with lung cancer and pulmonary metastases
      are surgery, radiotherapy, chemotherapy, and immunotherapy. For reducing clinical
      complications of surgery and achieving a better local response, transpulmonary
      chemoembolization of the lungs is a possible interventional technique in which
      anticancer drugs are administered directly into a tumor through its feeding
      vessels followed by occlusive agents that are injected through the delivery
      catheter for blocking the vessel. This allows a longer contact period in the
      tumor with a higher cytostatic drug concentration. The technique is safe and
      results present promising local response rates, but the influence on survival is
      still questionable. This article describes the current role of intravascular
      therapies in the treatment of pulmonary malignancies. 

PMID- 24436535
TI  - Radiation therapy for early stage lung cancer.
AB  - Radiation therapy for early stage lung cancer is a promising modality. It has
      been traditionally used in patients not considered candidates for standard
      surgical resection. However, its role has been changing rapidly since the
      introduction of new and advanced technology, especially in tumor tracking, image
      guidance, and radiation delivery. Stereotactic radiation therapy is one such
      advancement that has shown excellent local control rates and promising survival
      in early stage lung cancer. In addition, the toxicity profiles are quite
      favorable. In addition to stereotactic radiation, advances in brachytherapy
      techniques have enabled high local control rates in operable patients who receive
      sublobar resections due to compromised pulmonary function. Isotopes that have
      been used include iodine-125, palladium-103, and cesium-131. In this review
      article, the role of radiation therapy in treatment of lung cancer, patient
      selection, outcomes, toxicity and recent technological advancements are
      discussed. The radiation therapy techniques described in this article are also
      being used in the management of locally advanced lung cancers. 

PMID- 24436536
TI  - Non-small-cell lung cancer: treatment of late stage disease: chemotherapeutics
      and new frontiers.
AB  - Systemic therapy should be considered in patients with advanced non-small cell
      lung cancer (NSCLC) who are no longer amenable to local therapies. Systemic
      therapy has been shown to improve survival and preserve quality of life in
      patients with a reasonable performance status. In unselected patients, the
      standard of care for initial therapy remains platinum-based chemotherapy. At
      progression, further treatment typically consists of the sequential
      administration of single-agent therapy, which has also been shown to improve
      survival and reduce cancer-related symptoms. Molecular biomarkers are essential
      to guide targeted agents. This analysis requires ample tumor DNA; thus adequate
      biopsy samples are critical to guide therapeutic options. More biomarkers are
      currently being validated and may potentially have specific targeted therapy. In
      the near future, it is likely that rapid multiplexed genotype testing will help
      reduce the need for large amounts of tumor for analysis and will promote
      personalized cancer therapy. We review recent changes in the definition of stage
      IV NSCLC and review current and future systemic therapeutic approaches for
      patients with advanced disease. 

PMID- 24436537
TI  - Palliative procedures in lung cancer.
AB  - Palliative care aims to optimize comfort and function when cure is not possible.
      Image-guided interventions for palliative treatment of lung cancer is aimed at
      local control of advanced disease in the affected lung, adjacent mediastinal
      structures, or distant metastatic sites. These procedures include endovascular
      therapy for superior vena cava syndrome, bronchial artery embolization for
      hemoptysis associated with lung cancer, and ablation of osseous metastasis.
      Pathophysiology, clinical presentation, indications of these palliative
      treatments, procedural techniques, complications, and possible future
      interventions are discussed in this article. 

PMID- 24436538
TI  - Virtually no thoracic lesion inaccessible: a pictorial case review.
AB  - Access route considerations in percutaneous intrathoracic biopsy or ablation
      offers its own unique set of challenges, with special consideration toward
      reducing the rate of pneumothorax. This review highlights several novel and
      atypical methods to improve access to intrathoracic lesions through a series of
      representative cases. These methods include patient positioning, curved needles,
      hydrodissection, induced/artificial pneumothorax, and use of specialized
      equipment functions. No intrathoracic lesion should be considered "inaccessible"
      either for biopsy or treatment by percutaneous approaches without consideration
      of performing these adjunctive techniques. 

PMID- 24436539
TI  - Percutaneous management of lymphoceles after renal transplantation.

PMID- 24436541
TI  - Post-test questions.

PMID- 24436542
TI  - Why "Neurointerventions" for IR and Why Now?

PMID- 24436540
TI  - Mental status changes postchemoembolization: the role of inflammatory response.

PMID- 24436543
TI  - Basic neuroangiography: review of technique and perioperative patient care.
AB  - Neuroangiography (NA) is an important part of diagnosis and treatment of patients
      with neurological disease. Although NA may be performed for diagnostic purposes,
      in many instances NA is performed with the intent to treat. Indications for NA
      range from extracranial diseases (vertebrobasilar insufficiency from subclavian
      steal, extracranial carotid stenosis, cavernous-carotid fistula, neck trauma,
      epistaxis, tumor invasion of the carotid artery, and tumor embolization) to
      intracranial diseases (nontraumatic subarachnoid hemorrhage, cerebral aneurysms,
      cerebral arteriovenous malformations, cerebral vasospasm, acute stroke, tumor
      embolization, and WADA test). Similar to peripheral angiography, appropriate
      preprocedural assessment and postprocedural care, along with understanding of
      anatomy, catheter technique, and disease processes, are vital to successful
      outcomes. This article will review the basic technique, equipment, and patient
      management in NA. With appropriate skill and knowledge, interventional
      radiologists can perform NA with safe and successful results. 

PMID- 24436544
TI  - Basic vascular neuroanatomy of the brain and spine: what the general
      interventional radiologist needs to know.
AB  - This article is intended to provide a review of clinically relevant neurovascular
      anatomy. A solid understanding of the vascular anatomy of the brain and spine are
      essential for the safe and effective performance of neurointerventional
      radiology. Key concepts to master include collateral pathways and anastomoses
      between the external and internal carotid circulation, the Circle of Willis as a
      route to otherwise inaccessible intracranial vascular distributions, and the
      origin of spinal arterial blood supply. These concepts will be highlighted using
      clinical angiographic examples with discussion of relevant embryology and
      pathology as needed. 

PMID- 24436545
TI  - Fundamentals of the neurologic examination for patients undergoing central
      nervous system interventional procedures.
AB  - The basic neurologic history and exam for the interventional radiologist
      performing intracranial procedures need not be exhaustive and will not supplant
      that by neurologic specialist. It should include a pertinent history, focused
      neurologic exam, and a brief physical exam. The interventional radiologist should
      be familiar with the grading scales commonly used for patients with intracranial
      pathology to understand the severity and prognosis of various pathologies. The
      goal of the examination is to mitigate risk, direct the evaluation, aid in
      medical decision making, and allow the establishment of an appropriate physician
      patient relationship. 

PMID- 24436546
TI  - Interventional management of head and neck emergencies: carotid blowout.
AB  - Involvement of the carotid artery by malignant processes of the head and neck
      with compromise of vessel integrity and rupture-"carotid blowout syndrome" (CBS)
      is one of the most devastating complications of malignancy. Most often, it is
      associated with squamous cell cancer and almost always in patients who have
      undergone prior radiation therapy. CBS is classified as threatened, impending, or
      acute. Bleeding into the oral cavity or from areas of skin breakdown is a
      frightening experience for patients and their families and often a terminal
      event. Prognosis is poor with up to 50% mortality and morbidity, and surgical
      options are limited and risky. Endovascular management with vessel sacrifice or
      stent placement has become the principle treatment option in this patient
      population, though still associated with procedural complications, often
      neurologic, that can occur acutely or in a delayed fashion. This article reviews
      techniques and outcomes associated with endovascular treatment of CBS. 

PMID- 24436547
TI  - Transcatheter embolization in the management of epistaxis.
AB  - A majority of the population will experience epistaxis at some time in their
      life. Most cases will be from an anterior source and can be treated with
      pressure, anterior nasal packing, or cautery. Intractable epistaxis is generally
      posterior in origin and may require endoscopic cautery, posterior packing,
      surgical ligation, or embolization. Embolization has been used to treat epistaxis
      for more than 30 years and success can be achieved in approximately 90% of
      patients, with major complications occurring in approximately 2%. These excellent
      results require thorough knowledge of the regional anatomy, familiarity with the
      equipment and various agents used to achieve this type of embolization, as well
      as attention to detail and meticulous technique. There remains debate on several
      aspects of embolization, including the agent of choice, preferred size of the
      embolic, and the number of vessels to embolize. Advances in endoscopic surgery
      have evolved to the point that similar success rates for embolization and modern
      surgical techniques in treating epistaxis may be expected. This detailed review
      of pertinent vascular anatomy, embolization technique, and surgical alternatives
      should allow practitioners to formulate treatment algorithms that result in
      optimal outcomes at their institutions. 

PMID- 24436549
TI  - Interventional management of vertebral body metastases.
AB  - Metastases to the vertebral column are often due to hypervascular primary tumors,
      the most common of which is renal cell carcinoma. Clinical symptoms attributed to
      vertebral body metastases include localized pain, mechanical instability of the
      vertebral column, and neurologic deficits resulting from mass effect. Treatment
      options include targeted radiotherapy, percutaneous vertebral augmentation with
      or without thermal ablation, and surgical resection with subsequent fusion.
      Overall, surgical resection of the tumor and stabilization of the vertebral
      column provide the best prognosis for the patient in terms of symptomatic
      improvement and long-term survival; however, resection of hypervascular vertebral
      body metastases can result in significant intraoperative blood loss that can add
      to the morbidity of the procedure. Preoperative embolization of hypervascular
      metastases of the vertebral column has been shown to significantly reduce
      intraoperative blood loss at the time of surgery. The goal of this manuscript is
      to describe the role of embolization therapy in the management of patients with
      vertebral body metastases. 

PMID- 24436548
TI  - Contemporary endovascular embolotherapy for meningioma.
AB  - Preoperative endovascular tumor embolization has been used for 40 years.
      Meningiomas are the most common benign intracranial tumor in which preoperative
      embolization has been most extensively described in the literature. Advocates of
      embolization report that it reduces operative blood-loss, and softens the tumor,
      thus making surgery safer and easier. Opponents suggest that it adds additional
      risk and cost for patients without controlled studies showing conclusive benefit.
      The literature suggests a 3 to 6% neurological complication rate related to
      embolization. The combined external and internal carotid artery blood supply and
      complex anastomoses of the meninges can make embolization challenging. Positive
      outcomes require thorough knowledge of the pertinent vascular anatomy,
      familiarity with the neurovascular equipment and embolics, and meticulous
      technique. There remains debate on several aspects of embolization, including
      tumors most appropriate for embolization, embolic agent of choice, ideal size of
      embolic, and the choice of vessel(s) to embolize. This detailed review of
      pertinent vascular anatomy, embolization technique, results, and complications
      should allow practitioners to maximize treatment outcomes in this setting. 

PMID- 24436550
TI  - Intra-arterial Stroke Management.
AB  - Acute ischemic stroke is a leading cause of death and the leading cause of
      disability in the United States. Cerebral neuronal death begins within minutes
      after threshold values of blood oxygen saturation are crossed. Prompt restoration
      of oxygenated blood flow into ischemic tissue remains the common goal of
      reperfusion strategies. This article provides a brief overview of acute ischemic
      stroke, a summary of the major intra-arterial stroke therapy trials, and comments
      on current training requirements for the performance of intra-arterial therapies.

PMID- 24436551
TI  - Carotid artery stenting: review of technique and update of recent literature.
AB  - Stroke is the fourth leading cause of death and the number one cause of long-term
      disability in the United States. Carotid stenosis is an important cause of
      ischemic strokes, accounting for 20 to 25%. Previous studies have established
      carotid endarterectomy as standard of care of symptomatic patients with > 50%
      stenosis and asymptomatic patients with > 60% stenosis; recently, carotid artery
      stenting has emerged as an alternative treatment for carotid stenosis. Several
      studies have been published comparing carotid artery stenting with endarterectomy
      with mixed results. In this article, the authors discuss carotid artery stenting
      technique, the results from the most recent trials, and future directions. 

PMID- 24436553
TI  - Interventional spine procedures for management of chronic low back pain-a primer.
AB  - Chronic low back pain is a common clinical condition. Percutaneous fluoroscopic
      guided interventions are safe and effective procedures for the management of
      chronic low back pain, which can be performed in an outpatient setting.
      Interventional radiologists already possess the technical skills necessary to
      perform these interventions effectively so that they may be incorporated into a
      busy outpatient practice. This article provides a basic approach to the
      evaluation of patients with low back pain, as well as a review of techniques used
      to perform the most common interventions using fluoroscopic guidance. 

PMID- 24436552
TI  - Vertebroplasty.
AB  - Percutaneous vertebroplasty has become widely accepted as a safe and effective
      minimally invasive procedure for the treatment of painful vertebral body
      compression fractures refractory to medical therapy. In this article, the authors
      review the indications and contraindications for vertebroplasty, principles of
      appropriate patient selection, useful techniques to achieve optimal outcomes, and
      the potential risks and complications of the procedure. 

PMID- 24436554
TI  - Percutaneous neurolytic celiac plexus block.

PMID- 24436555
TI  - Digital Ischemia during Sclerotherapy of an Arteriovenous Malformation.

PMID- 24436556
TI  - Comprehensive Stroke Centers: Recognizing the Need for Complex Stroke Care and
      Interventional Radiology's Contribution.

PMID- 24436557
TI  - Post-test questions.

PMID- 24436558
TI  - Collaboration between Industry and Physicians-An Essential Alliance.

PMID- 24436559
TI  - Endovascular therapies for primary postpartum hemorrhage: techniques and
      outcomes.
AB  - Interventional radiologists are often consulted for acute management of
      hemorrhagic complications in obstetric and gynecologic patients. The aim of this
      article is to review the common indications for vascular embolization in
      obstetric and gynecologic emergencies, specifically in the setting of primary
      postpartum hemorrhage, and to discuss the technique and outcomes of endovascular
      treatment. 

PMID- 24436560
TI  - Current evidence on uterine embolization for fibroids.
AB  - Strong evidence for both safety and effectiveness of uterine fibroid embolization
      has been generated since the procedure's introduction. This review will focus on
      the key articles representing the best evidence to summarize the outcomes from
      uterine embolization. This review will attempt to answer three important
      questions associated with uterine embolization. First, does uterine embolization
      relieve symptoms caused by uterine fibroids? Second, how well does the
      improvement in symptoms and quality of life after uterine embolization compare
      with standard surgical options for fibroids? Finally, how durable is the
      improvement in fibroid-related symptoms and quality of life after embolization? 

PMID- 24436561
TI  - Clinical and Technical Aspects of MR-Guided High Intensity Focused Ultrasound for
      Treatment of Symptomatic Uterine Fibroids.
AB  - Although many women undergo hysterectomy for treatment of uterine fibroids, there
      are more options than ever before for fibroid treatment. A combination of
      objective criteria, including clinical parameters, anatomic factors, fibroid
      characteristics, and patient desires influence the choice of optimal therapeutic
      modality for a woman with symptomatic uterine fibroids. Magnetic resonance
      imaging-guided high intensity focused ultrasound (MR-HIFU) is the only
      noninvasive treatment option for women with symptomatic uterine fibroids
      unresponsive to medical treatment. The procedure has been shown to be safe and
      effective. MR-HIFU couples the three-dimensional multiplanar anatomic imaging and
      thermal monitoring capability of MR imaging with the therapeutic thermal-based
      coagulative necrosis mechanism of HIFU to safely and effectively ablate limited
      volume classical fibroids. In the author's experience, a multidisciplinary
      fibroid clinic facilitates a unified approach between gynecologists,
      radiologists, and others to individualize the most appropriate fibroid treatment
      options for each woman. This article describes the MR-HIFU technique and
      outcomes, as well as patient selection and treatment assessment. 

PMID- 24436562
TI  - Clinical and periprocedural pain management for uterine artery embolization.
AB  - Uterine artery embolization has Level A data supporting excellent safety and
      efficacy in treating symptomatic uterine leiomyomata. However, there is a
      perception that either postprocedural pain is severe or poorly managed by the
      physician performing these procedures. This has led some primary care physicians
      to omit this procedure from the patients' options or to steer patients away from
      this procedure. A few simple techniques (pruning of the vascular tree and
      embolizing to 5-10 beat stasis) and fastidious pre-, intra-, and post-procedural
      management can nearly eliminate significant pain associated with embolization.
      Specifically, early implementation of long-acting low-dose narcotics, antiemetics
      and anti-inflammatory medications is critical. Finally, the use of a superior
      hypogastric nerve block, which takes minutes to perform and carries a very low
      risk, significantly reduces pain and diminishes the need for narcotics; when this
      technique was used in a prospective study, all patients were able to be
      discharged the day of the procedure. In the authors' experience, patients treated
      in this manner largely recover completely within 5 days and have a far less
      traumatic experience than patients traditionally treated with only midazolam
      (Versed) and fentanyl citrate (fentanyl) intraprocedurally, and narcotics and
      nonsteroidal antiinflammatory drugs postprocedurally. 

PMID- 24436564
TI  - Pelvic congestion syndrome.
AB  - Patients with pelvic congestion syndrome present with otherwise unexplained
      chronic pelvic pain that has been present for greater than 6 months, and anatomic
      findings that include pelvic venous insufficiency and pelvic varicosities. It
      remains an underdiagnosed explanation for pelvic pain in young, premenopausal,
      usually multiparous females. Symptoms include noncyclical, positional lower back,
      pelvic and upper thigh pain, dyspareunia, and prolonged postcoital discomfort.
      Symptoms worsen throughout the day and are exacerbated by activity or prolonged
      standing. Examination may reveal ovarian tenderness and unusual varicosities
      vulvoperineal, posterior thigh, and gluteal. Diagnosis is suspected by clinical
      history and imaging that demonstrates pelvic varicosities. Venography is usually
      necessary to confirm ovarian vein reflux, although transvaginal ultrasound may be
      useful in documenting this finding. Endovascular therapy has been validated by
      several large patient series with long-term follow-up using standardized pain
      assessment surveys. Embolization has been shown to be significantly more
      effective than surgical therapy in improving symptoms in patients who fail
      hormonal therapy. Although there has been variation in approaches between
      investigators, the goal is elimination of ovarian vein reflux with or without
      direct sclerosis of enlarged pelvic varicosities. Symptom reduction is seen in 70
      to 90% of the treated females despite technical variation. 

PMID- 24436563
TI  - Pelvic vascular malformations.
AB  - Vascular malformations (VMs) comprise a wide spectrum of lesions that are
      classified by content and flow characteristics. These lesions, occurring in both
      focal and diffuse forms, can involve any organ and tissue plane and can cause
      significant morbidity in both children and adults. Since treatment strategy
      depends on the type of malformation, correct diagnosis and classification of a
      vascular lesion are crucial. Slow-flow VMs (venous and lymphatic malformations)
      are often treated by sclerotherapy, whereas fast-flow lesions (arteriovenous
      malformations) are generally managed with embolization. In addition, some cases
      of VMs are best treated surgically. This review will present an overview of VMs
      in the female pelvis as well as a discussion of endovascular therapeutic
      techniques. 

PMID- 24436565
TI  - Fallopian tube catheterization.
AB  - Fallopian tube catheterization is used for treatment of infertility caused by
      proximal tubal occlusion, and has replaced surgical treatment for this condition.
      More recently, fallopian tube catheterization has been used for tubal
      sterilization. Interventional radiologists tested numerous methods for tubal
      occlusion using the rabbit as an animal model. As a result, a tubal device has
      recently been Food and Drug Administration approved for permanent sterilization
      using hysteroscopic guidance; it can also be placed fluoroscopically by fallopian
      tube catheterization as an "off-label" procedure. This is a 5-year continuation
      and update on a procedure that has been done by interventional radiologists for
      25 years; history of the development of fallopian tube catheterization in women
      has been published in detail in this journal. Highlighted in this article will be
      description of the basic components needed for fallopian tube catheterization. 

PMID- 24436566
TI  - Role of interventional radiologists in the management of lower extremity venous
      insufficiency.
AB  - Lower extremity venous insufficiency affects over half of all women.
      Interventional radiologists should be aware of the clinical evaluation of women
      with venous insufficiency and classification of disease. Endovascular therapies
      available for treatment of lower extremity venous insufficiency include:
      endovenous laser ablation, radiofrequency endovascular ablation, and
      sclerotherapy. The interventional radiologist should be versed on which therapy
      to select in each clinical presentation and the procedural techniques. The
      authors review the role of the interventional radiologist in managing this lower
      extremity venous disorder. 

PMID- 24436567
TI  - Challenges in interventional radiology: the pregnant patient.
AB  - A pregnant patient presenting to interventional radiology (IR) has a different
      set of needs from any other patient requiring a procedure. Often, the patient's
      care can be in direct conflict with the growth and development of the fetus,
      whether it be optimal fluoroscopic imaging, adequate sedation of the mother, or
      the timing of the needed procedure. Despite the additional risks and complexities
      associated with pregnancy, IR procedures can be performed safely for the pregnant
      patient with knowledge of the special and general needs of the pregnant patient,
      use of acceptable medications and procedures likely to be encountered during
      pregnancy, in addition to strategies to protect the patient and her fetus from
      the hazards of radiation. 

PMID- 24436568
TI  - Pregnancy and the working interventional radiologist.
AB  - The prevalence of women radiologists has risen in the past decade, but this rise
      is not reflected in interventional radiology. Women are grossly underrepresented,
      and this may be partly due to fear of radiation exposure, particularly during
      pregnancy. The simple fact is radiation exposure is minimal and the concern
      regarding the health of the developing fetus is unjustly aggrandized. Fully
      understanding the risks may help women to choose interventional radiology and
      practicing women interventionalists to stay productive during their child-bearing
      years. To date, little has been published to guide women who may become pregnant
      during their training and career. 

PMID- 24436569
TI  - Management of pulmonary arteriovenous malformations in hereditary hemorrhagic
      telangiectasia patients.

PMID- 24436570
TI  - Hemorrhage as a complication of percutaneous liver biopsy.

PMID- 24436571
TI  - Gynecologic biopsy for molecular profiling: a review for the interventional
      radiologist.
AB  - The interventional radiologist is often asked to obtain multiple biopsies of
      gynecological malignancies for genetic profiling. This article reviews the
      current indications for gynecological biopsy as well as how the information
      gained contributes to a personalized medicine plan for the individual patient.
      The specific focus of this review is the current knowledge and practice of
      molecular profiling for gynecological malignancies. 

PMID- 24436573
TI  - Medication-assisted treatment for opioid addiction: methadone and buprenorphine.
AB  - Among agents for treatment of opioid addiction, methadone is a full mu-opioid
      receptor agonist, whereas buprenorphine is a partial agonist. Both are long
      acting. Buprenorphine has a superior safety profile. Methadone is formulated for
      oral administration and buprenorphine for sublingual administration. A subdermal
      buprenorphine implant with a 6-month duration of action is being considered for
      approval by the U.S. Food and Drug Administration. Both medications reduce
      mortality rates and improve other outcomes. Data from a recent randomized
      controlled comparison of both medications (N = 1269) show better treatment
      retention with methadone but reduced illicit opioid use early in treatment with
      buprenorphine. Human immunodeficiency virus (HIV) risk behaviors were measured
      using the Risk Behavior Survey at baseline, 12 weeks, and 24 weeks for study
      completers. In the 30 days prior to treatment entry, 14.4% of the completers
      randomized to treatment with buprenorphine (n = 340) and 14.1% of the completers
      randomized to methadone treatment (n = 391) shared needles. The percent sharing
      needles decreased to 2.4% for buprenorphine and 4.8 for methadone in the 30 days
      prior to Week 24 (p < 0.0001). In the 30 days prior to treatment entry, 6.8% of
      the completers randomized to buprenorphine and 8.2% of the completers randomized
      to methadone had multiple sexual partners, with only 5.2% and 5.1%, respectively,
      reporting multiple partners at Week 24 (p < 0.04).

PMID- 24436572
TI  - Fatty acid metabolism and thyroid hormones.
AB  - The importance of thyroid hormone signaling in the acute regulation of metabolic
      activity has been recognized for decades. Slowly, the underlying mechanisms
      responsible for this activity are being elucidated. A prominent characteristic of
      thyroid signaling is rapid increases in oxygen consumption and ATP production.
      This discovery implicated a non-genomic regulation of mitochondrial metabolism by
      thyroid hormones. Another important clue came from the discovery that thyroid
      hormones stimulated fatty acid oxidation (FAO) in a variety of tissues in a
      receptor-dependent, but transcriptional-independent manner. Recently, key
      linkages between thyroid hormone signaling and specific mitochondrial-targeted
      pathways have been discovered. This review focuses on the molecular mechanisms by
      which mitochondrial FAO can be increased through thyroid hormone signaling. The
      roles of both the full-length and shortened mitochondrial isoforms of thyroid
      hormone receptor will be discussed. Additionally, the impact of thyroid hormone
      signaling on dyslipidemias such as obesity, type II diabetes, and fatty liver
      disease will be considered.

PMID- 24436574
TI  - The Application of Nafion Metal Catalyst Free Carbon Nanotube Modified Gold
      Electrode: Voltammetric Zinc Detection in Serum.
AB  - Metal catalyst free carbon nanotube (MCFCNT) whiskers were first used as an
      electrode modification material on a gold electrode surface for zinc voltammetric
      measurements. A composite film of Nafion and MCFCNT whiskers was applied to a
      gold electrode surface to form a mechanically stable sensor. The sensor was then
      used for zinc detection in both acetate buffer solution and extracted bovine
      serum solution. A limit of detection of 53 nM was achieved for a 120 s deposition
      time. The zinc in bovine serum was extracted via a double extraction procedure
      using dithizone in chloroform as a zinc chelating ligand. The modified electrode
      was found to be both reliable and sensitive for zinc measurements in both
      matrices.

PMID- 24436575
TI  - Lab-on-a-Chip Sensor with Evaporated Bismuth Film Electrode for Anodic Stripping
      Voltammetry of Zinc.
AB  - In this work, we report on the development of a lab-on-a-chip electrochemical
      sensor that uses an evaporated bismuth electrode to detect zinc using square wave
      anodic stripping voltammetry. The microscale electrochemical cell consists of a
      bismuth working electrode, an integrated silver/silver chloride reference
      electrode, and a gold auxiliary electrode. The sensor demonstrated linear
      response in 0.1 M acetate buffer at pH 6 with zinc concentrations ranging from 1
      MUM to 30 MUM and a calculated detection limit of 60 nM. The sensor was also able
      to successfully detect zinc in a bovine serum extract and the results were
      verified with independent AAS measurements. These results demonstrate the
      advantageous qualities of this lab-on-a-chip electrochemical sensor for clinical
      applications, which include a small sample volume (MUL scale), reduced cost,
      short response time and high accuracy at low concentrations of analyte.

PMID- 24436576
TI  - Discrimination, Mastery, and Depressive Symptoms Among African American Men.
AB  - PURPOSE: This study examines the influence of discrimination and mastery on
      depressive symptoms for African American men at young (18-34), middle (35-54),
      and late (55+) adulthood. METHOD: Analyses are based on responses from 1,271
      African American men from the National Survey of American Life (NSAL). RESULTS:
      Discrimination was significantly related to depressive symptoms for men ages 35
      to 54 and mastery was found to be protective against depressive symptoms for all
      men. Compared to African American men in the young and late adult groups,
      discrimination remained a statistically significant predictor of depressive
      symptoms for men in the middle group once mastery was included. IMPLICATIONS:
      Findings demonstrate the distinct differences in the influence of discrimination
      on depressive symptoms among adult African American males and the need for future
      research that explores the correlates of mental health across age groups.
      Implications for social work research and practice with African American men are
      discussed.

PMID- 24436577
TI  - An overview of optimal endovascular strategy in treating the femoropopliteal
      artery: mechanical, biological, and procedural factors.
AB  - Treatment of the femoropopliteal (FP) artery remains a challenge to the
      endovascular specialist. Long-term patency is low with a high rate of target
      lesion revascularization. The true patency rate varies considerably between
      studies partly because there is a lack of uniform performance criteria and
      reporting standards in peripheral arterial interventions. Literature review
      supports three principles that emerge as important components of an optimal
      strategy in treating the FP artery: (1) improving vessel compliance and
      subsequently less dissections and bailout stenting, (2) reducing smooth muscle
      cell proliferation, and (3) protecting outflow vessels from distal embolization.
      In this overview, we examine current data that support the validity of this
      strategy. 

PMID- 24436578
TI  - Endovascular Treatment versus Open Repair for Abdominal Aortic Aneurysms: The
      Influence of Fitness in Decision Making.
AB  - Two methods of repair are currently available for an abdominal aortic aneurysm
      (AAA), open aneurysm repair and endovascular aneurysm repair (EVAR). The decision
      making depends on the balance of risks and benefits. The treating physician must
      take into account the patient's life expectancy, the patient's fitness, the
      anatomic suitability that makes endovascular repair possible, and finally the
      patient's preference. The patient's fitness is an important variable predicting
      the outcome of AAA surgical reconstruction. The hypothesis is that the impact of
      risk factors upon perioperative mortality might differ between patients
      undergoing open repair and endovascular repair. The purpose of this review
      article is to investigate whether fitter patients with a large AAA benefit more
      from having endovascular rather than open repair. According to the available
      data, there is emerging evidence that patients at high medical risk for open
      repair may benefit from EVAR while in low risk patients with suitable anatomy for
      EVAR, both techniques have similar effects. There is rising evidence that a
      patient with ruptured AAA would benefit more from an endovascular procedure if
      eligible, and thus fitness in such emergencies is not the first priority but
      anatomical suitability for EVAR. 

PMID- 24436579
TI  - Optimizing cardiovascular benefits of exercise: a review of rodent models.
AB  - Although research unanimously maintains that exercise can ward off cardiovascular
      disease (CVD), the optimal type, duration, intensity, and combination of forms
      are yet not clear. In our review of existing rodent-based studies on exercise and
      cardiovascular health, we attempt to find the optimal forms, intensities, and
      durations of exercise. Using Scopus and Medline, a literature review of English
      language comparative journal studies of cardiovascular benefits and exercise was
      performed. This review examines the existing literature on rodent models of
      aerobic, anaerobic, and power exercise and compares the benefits of various
      training forms, intensities, and durations. The rodent studies reviewed in this
      article correlate with reports on human subjects that suggest regular aerobic
      exercise can improve cardiac and vascular structure and function, as well as
      lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of
      rodent-based aerobic studies, but a lack of anaerobic and power forms of
      exercise, as well as comparisons of these three components of exercise. Thus,
      further studies must be conducted to determine a truly optimal regimen for
      cardiovascular health. 

PMID- 24436580
TI  - Calf pump activity influencing venous hemodynamics in the lower extremity.
AB  - Calf muscle pump is the motive force enhancing return of venous blood from the
      lower extremity to the heart. It causes displacement of venous blood in both
      vertical and horizontal directions, generates ambulatory pressure gradient
      between thigh and lower leg veins, and bidirectional streaming within calf
      perforators. Ambulatory pressure gradient triggers venous reflux in incompetent
      veins, which induces ambulatory venous hypertension in the lower leg and foot.
      Bidirectional flow in calf perforators enables quick pressure equalization
      between deep and superficial veins of the lower leg; the outward (into the
      superficial veins) oriented component of the bidirectional flow taking place
      during calf muscle contraction is no pathological reflux but a physiological
      centripetal flow streaming via great saphenous vein into the femoral vein. Calf
      perforators are communicating channels between both systems making them conjoined
      vessels; they are not involved in the generation of pathological hemodynamic
      situations, nor do they cause ambulatory venous hypertension. The real cause why
      recurrences develop has not as yet been cleared. Pressure gradient arising during
      calf pump activity between the femoral vein and the saphenous remnant after
      abolition of saphenous reflux triggers biophysical and biochemical events, which
      might induce recurrence. Thus, abolition of saphenous reflux removes the
      hemodynamic disturbance, but at the same time it generates precondition for
      reflux recurrence and for the comeback of the previous pathological situation;
      this chain of events has been called hemodynamic paradox. 

PMID- 24436581
TI  - BMI Is an Independent Preoperative Predictor of Intraoperative Transfusion and
      Postoperative Chest-Tube Output.
AB  - Background An increasing obese population in the United States focuses attention
      on perioperative management of obese and overweight patients. Objective We sought
      to determine if obesity, determined by body mass index (BMI), was a preoperative
      indicator of bleeding in coronary artery bypass graft (CABG) surgery as measured
      by intraoperative packed red blood cell transfusion frequency and 24-hour chest
      tube output amount. Methods A retrospective chart review examined 290 consecutive
      patients undergoing single-surgeon off-pump or on-pump CABG surgery between
      November 2003 and April 2009. Preoperative variables of age, gender, hematocrit,
      platelet count, and BMI, chest tube output during the immediate 24-hour
      postoperative period, and the type of procedure (on-pump vs. off-pump) were
      analyzed. Logistic regression analysis was used to evaluate the likelihood of
      intraoperative transfusion. Linear regression analysis was used to evaluate 24
      hour chest-tube output. Results Preoperative variables that significantly
      increased the likelihood of intraoperative transfusions were older age and low
      hematocrit; a significant decrease in likelihood was found with male gender,
      overweight BMI, and off-pump procedures. Preoperative variables that
      significantly increased 24-hour chest-tube output were low hematocrit, high
      hematocrit, and low platelets while a significant decrease in output was seen
      with overweight BMI and obese BMI. Conclusion Overweight and obese BMI are
      significant independent predictors of decreased intraoperative transfusion and
      decreased postoperative blood loss. 

PMID- 24436582
TI  - The dynamic function of the atrial diastole of the heart and motion of venous
      valves in humans.
AB  - This study demonstrates dynamic function of atrial diastole for the first time in
      the history of medicine, following the revelation of ventricular function by Sir
      William Harvey. This study consists of two parts. First part is the study of
      humans and the discovery of the rhythmic opening and closing of venous valves in
      the femoral vein segment during each cardiac cycle under fluoroscopy. Its
      relationship to the right atrial diastole is discussed. Second part is an
      experimental model developed in a dog's heart. Experiments are conducted in an
      erect posture, in which the right atrium is partially and totally isolated
      physically and/or functionally. The right atrium was found to function as a
      suction pump, readily demonstrated on graphic curves by voluntary stretching of
      muscle fibers of the empty atrium, creating considerable negative pressure during
      diastolic function, and responsible for venous return to the heart. Motive forces
      in the venous return are common knowledge in present medical literature, but are
      limited to respiration and skeletal muscle contraction of the extremities. The
      discovery of the right atrium as a suction force due to stretching of muscle
      fibers during diastolic function, thereby creating negative pressure, represents
      a departure from the currently accepted paradigm established by Sir William
      Harvey (1576-1652), with the heart as an organ functioning solely by contraction
      of its chambers. This is the first time since then a fundamental new discovery
      concerning cardiac mechanical function has been made utilizing experimental
      evidence. 

PMID- 24436583
TI  - Removal of foley catheters in live donor kidney transplant recipients on
      postoperative day 1 does not increase the incidence of urine leaks.
AB  - Catheterization of the urinary bladder during kidney transplantation is
      essential. The optimal time to remove the Foley catheter postoperatively is not
      universally defined. It is our practice to remove the Foley catheter on
      postoperative day 1 in live donor kidney transplant recipients who meet our
      standardized protocol criteria. We believe that early removal of Foley catheters
      increases patient comfort and mobility, decreases the risk of catheter associated
      urinary tract infections, and allows for decreased hospital length of stay. The
      hypothetical risk of early removal of Foley catheters would be the increased risk
      of urine leak. We reviewed 120 consecutive live donor kidney transplant
      recipients and found that there was not an increased incidence of urine leaks in
      patients whose Foley catheters were removed on postoperative day 1. 

PMID- 24436584
TI  - Secretory Phospholipase A2 Is Associated with the Odds of Acute Coronary
      Syndromes through Elevation of Serum Amyloid-A Protein.
AB  - In coronary heart disease (CHD), levels of secretory phospholipase A2 (sPLA2) are
      commonly increased. Serum amyloid-A (SAA) is increased in acute coronary
      syndromes (ACS) as well. It is needed to verify the hypotheses that sPLA2 is
      associated with the odds of ACS through elevation of SAA. We conducted a case
      control study with 57 male patients with ACS and 30 controls matched by gender
      category. Levels of sPLA2, SAA, and myeloperoxidase (MPO) were measured by
      immunoreactive assay on the basis of a double-antibody sandwich technique. Levels
      of sPLA2, MPO, and SAA were significantly higher in patients than those in
      controls (11,359.0 +/- 10,372.4 pg/mL vs. 1,320.5 +/- 654.5 pg/mL, p = 0.00;
      438.6 +/- 310.7 ng/mL vs. 271.1 +/- 176.8 ng/mL, p = 0.01; 10,995.2 +/- 2,842.6
      ng/mL vs. 3,861.7 +/- 3,173.5 ng/mL, p = 0.00). There were significant
      correlations between age, visceral obesity, MPO, sPLA2, and SAA (r = 0.43; p =
      0.00; r = 0.30; p = 0.00; r = 0.28; p = 0.00 and r = 0.53; p = 0.00). On
      multivariate logistic regression analyses, there were significant and independent
      associations between sPLA2 and SAA with odds of ACS [OR (95% CI) = 14.2 (2.1 to
      98.6), p = 0.00; OR (95% CI) = 44.9 (6.9 to 328.4), p = 0.00]. Our findings
      suggest that sPLA2 may be associated with the odds of ACS compared with controls
      through increased inflammation, represented by elevated SAA. 

PMID- 24436585
TI  - Woven coronary artery anomaly associated with acute coronary syndrome.
AB  - The woven coronary artery anomaly is a rare congenital anomaly in which a
      coronary artery is divided into thin channels that merge again into the distal
      lumen. Only a few cases of woven coronary artery have been reported in the
      literature. This anomaly is accepted as a benign condition. We describe a case of
      acute coronary syndrome in a patient with woven coronary artery anomaly. 

PMID- 24436586
TI  - Coronary Artery Spasm in Multivessel ACS: What More Should We Know?
AB  - Coronary spasm may present as acute coronary syndrome (ACS), "which can be an ST
      segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina."
      However, the prevalence of coronary spasm in patients with ACS remains unknown
      due to scarcity of data. Concomitant coronary spasm may mask the true
      atherosclerosis burden in such cases, posing several management challenges. We
      illustrate the case of managing an ACS patient with concomitant spasm and
      atherosclerotic disease. We show that the routine use of vasodilator treatment in
      ACS cases may prevent inappropriate stenting by identifying concomitant coronary
      spasm, influencing the clinical outcomes associated with inappropriate stenting
      in the setting of coronary spasm. 

PMID- 24436587
TI  - Successful expansion of an underexpanded stent by rotational atherectomy.
AB  - The current routine use of intracoronary stents in percutaneous coronary
      intervention (PCI) has significantly reduced rates of restenosis, compared with
      balloon angioplasty alone. On the contrary, small post-stenting luminal
      dimensions due to undilatable, heavily calcified plaques have repeatedly been
      shown to significantly increase the rates of in-stent restenosis. Rotational
      atherectomy of lesions is an alternative method to facilitate PCI and prevent
      underexpansion of stents, when balloon angioplasty fails to successfully dilate a
      lesion. Stentablation, using rotational atherectomy to expand underexpanded
      stents deployed in heavily calcified plaques, has also been reported. We report a
      case via the transradial approach of rotational-atherectomy-facilitated PCI of in
      stent restenosis of a severely underexpanded stent due to a heavily calcified
      plaque. We review the literature and suggest rotational atherectomy may have a
      role in treating a refractory, severely underexpanded stent caused by a heavily
      calcified plaque through various proposed mechanisms. 

PMID- 24436588
TI  - Subclavian aneurysm presenting with massive hemoptysis: a case report and review
      of the literature.
AB  - We present a case of a 70-year-old male with a past medical history of coronary
      artery bypass grafting and end stage renal disease who presented with massive
      hemoptysis. He had a history of methicillin-resistant Staphylococcus aureus
      endocarditis, with infection and removal of endocardial pacing leads. His work-up
      revealed a 2.9-cm proximal left subclavian artery aneurysm. Bronchoscopy
      confirmed bright red blood in the left upper lobe bronchus and coronary
      angiography confirmed a patent left internal mammary artery (LIMA) to left
      anterior descending bypass. Because of the consideration of maintaining coronary
      perfusion via the LIMA while excluding the subclavian aneurysm, he underwent a
      left carotid to left axillary artery bypass graft followed by deployment of an
      Amplatzer II vascular plug just distal to the aneurysm. A thoracic endograft was
      then deployed to exclude the origin of the subclavian. A review of the literature
      reveals hemoptysis as a rare presentation of a subclavian aneurysm. We discuss
      approaches to this challenging clinical problem, ranging from open repair to
      hybrid approaches. 

PMID- 24436589
TI  - Problems and possible solutions for therapy with statins.
AB  - Despite issues about the value of statins, benefit for high cardiovascular (CV)
      risk outweighs problems. However, the practitioner must be aware of concerns, be
      prepared to respond, and justify statin usage. Symptoms of statin-related
      myopathy are of more concern than stated by pharmaceutical companies. Occurrence
      of myopathy symptoms, estimated to be up to 10.4%, can decrease statin adherence
      of high CV risk patients. Dosage modification, or use of pitavastatin, may help
      the problematic patient. There are concerns that there may be little benefit of
      statins for primary prevention in women. However, evidence appears to support
      statin use in women at high CV risk, both in primary and secondary prevention.
      Abandoning low-density lipoprotein cholesterol (LDL-C) as a valid target is
      unwarranted; there is much evidence to support "lower is better." The
      practitioner must be aware of the complicated processes causing atherosclerosis
      and when to incorporate new approaches to disease management. Tailoring therapy
      for CV risk, when indicated, may contribute further to LDL-C reduction. Liver
      inflammation can occur with statins but is of minimal concern; frequently,
      statins alleviate the problem. Unless liver transaminases are over three times
      normal, a statin should be prescribed, if indicated. The net effect of statins on
      cognition appears to be zero-no harm, no benefit. Despite reports of improved
      cognition, statins should not be prescribed for this. With diabetes mellitus
      (DM), statins can increase incidence, but the CV benefit far outweighs any risk.
      Therefore, statins should be prescribed in DM to reduce CV risk. Statins are a
      major medical contribution when used appropriately. 

PMID- 24436590
TI  - The significance of bradycardia in anorexia nervosa.
AB  - Anorexia nervosa (AN) is a life-threatening condition, with a significant risk
      for death, due to cardiovascular complications. It is characterized by abnormal
      eating behavior and has the highest mortality rate of all psychiatric disorders.
      It has been associated with bradycardia (a heart rate [HR] of less than 60 beats
      per minute) (up to 95%), hypotension, mitral valve prolapse, and heart failure.
      The diagnosis of AN can be elusive, and more than half of all cases are
      undetected. The purpose of this study was to raise and improve awareness to the
      possible diagnosis of AN in adolescent and young adult patients with weight loss
      displaying bradycardia and new cardiac disorders. Clinical characteristics, HR,
      and electrocardiographic data of 23 consecutive patients (20 females) with AN and
      of 10 young adults (8 females) without AN, between the years 2006 and 2009, were
      recorded and summarized. At presentation 16/23 (69.6%) showed HR < 50 bpm. The
      mean lowest HR of all patients was 44 +/- 6 (range 26 to 68) bpm. No patient
      needed pacemaker therapy. Bradycardia in young adults, especially females with
      weight loss, should raise the possible diagnosis of AN, so it can be treated
      early in-time, and thus prevent premature death. 

PMID- 24436591
TI  - Risk of Venous Thromboembolism in Patients Infected with HIV: A Cohort Study.
AB  - Introduction Human immunodeficiency virus (HIV) patients are at risk of
      developing thrombosis than general population. There are several intersecting
      mechanisms associated with HIV infection and antiviral therapy that are emerging,
      which may lead to vasculopathy and hypercoagulability in these patients. Methods
      We analyzed the HIV patients who followed up with our Vascular Medicine
      outpatient clinic with venous thromboembolism (VTE) over the past 3 years and
      followed them prospectively. The patients included were those who had minimum,
      regular follow-up of 3 months, with a Doppler scan in the beginning and last
      follow-up. Patients were analyzed for age, gender, race, site of thrombosis,
      coagulation factors, lipid panel, type of antiretroviral treatment, past or
      present history of infections or malignancy, CD4 absolute and helper cell counts
      at the beginning of thrombosis, response to treatment and outcome. Patients with
      HIV with arterial thrombosis were excluded. Results A total of eight patients
      were analyzed. The mean age was 49.87 years (range, 38-58 years). All were male
      patients with six patients having lower limb thrombosis, one patient with upper
      limb thrombosis related to peripheral inserted central catheter (PICC), and one
      patient had pulmonary embolism with no deep vein thrombosis. Most common venous
      thrombosis was popliteal vein thrombosis, followed by common femoral, superficial
      femoral and external iliac thrombosis. Two patients had deficiency of protein S,
      two had high homocysteine levels, one had deficiency of antithrombin 3, and one
      had increase in anticardiolipin Immunoglobulin antibody. All patients were taking
      nucleoside and nonnucleoside inhibitors but only two patients were taking
      protease inhibitors. There was history of lymphoma in one and nonsmall cell lung
      carcinoma in one patient. Three patients had past history of tuberculosis and one
      of these patients also had pneumocystis carinii pneumonia. The mean absolute CD4
      counts were 383.25 cells/UL (range, 103-908 cells/UL) and helper CD4 counts were
      22.5 cells/UL (range, 12-45 cells/UL). All were anticoagulated with warfarin or
      enoxaparin. There was complete resolution of deep vein thrombosis in two patients
      (one with PICC line thrombosis in 3 months and other with popliteal vein
      thrombosis in 1 year). There was extension of clot in one patient and no
      resolution in others. Seven patients are still alive and on regular follow-up.
      Conclusion Thrombosis in HIV patients is seen more commonly in middle aged,
      community ambulant male patients. Left lower limb involvement with involvement of
      popliteal vein is most common. Deficiency of protein S and hyperhomocystenaemia
      were noted in these patients. Most of these patients did not respond to
      therapeutic anticoagulation, but the extension of the thrombosis was prevented in
      majority of cases. 

PMID- 24436592
TI  - Shortened length of stay improves financial outcomes in living donor kidney
      transplantation.
AB  - Kidney transplantation is the preferred clinical and most cost-effective option
      for end-stage renal disease. Significant advances have taken place in the care of
      the transplant patients with improvements in clinical outcomes. The optimization
      of the costs of transplantation has been a constant goal as well. We present
      herein the impact in financial outcomes of a shortened length of stay after
      kidney transplant. 

PMID- 24436593
TI  - A Case Series of HIV-Seropositive Patients and Hypercoagulable State-Is It
      Difficult to Treat Even with Therapeutic Anticoagulation?
AB  - Patients with human immunodeficiency virus (HIV) are at risk of developing
      thrombosis and are 8 to 10 times more likely to develop thrombosis than the
      general population. Moreover, if they have hypercoagulable state they can have
      severe thrombosis and life-threatening thrombotic events. The purpose of this
      retrospective study is to analyze hypercoagulable state in HIV-seropositive
      patients who have been diagnosed with venous thromboembolism (VTE). This study is
      a subgroup study of a larger cohort group of HIV-seropositive patients with VTE
      followed up with our vascular medicine outpatient clinic. The patients included
      for this study were HIV-seropositive patients with hypercoagulable state,
      analyzed over the past 3 years, and followed prospectively. HIV-seropositive
      patients with arterial thrombosis were excluded. These patients had minimum,
      regular follow-up of 3 months, with a Doppler scan in the beginning and last
      follow-up. All the patients were analyzed for hypercoagulable state and the
      patients selected in this study were those who were tested positive for
      hypercoagulable state. All patients were analyzed for age, gender, race, site of
      thrombosis, coagulation factors, lipid panel, type of antiretroviral treatment,
      past or present history of infections or malignancy, CD4 absolute and helper cell
      counts at the beginning of thrombosis, and response to treatment and outcome.
      Patients with HIV with arterial thrombosis were excluded. The study was approved
      by the ethics committee. Five patients were included in this study. The mean age
      was 47.8 years (range 38 to 58 years). All were male patients with lower limb
      thrombosis. Most common venous thrombosis was popliteal vein thrombosis, followed
      by common femoral, superficial femoral, and external iliac thrombosis. Two
      patients had deficiency of protein S, two had high homocysteine levels, one had
      deficiency of antithrombin 3, and one had increase in anticardiolipin
      immunoglobulin G antibody. All the patients were taking nucleoside and
      nonnucleoside inhibitors but only one patient was taking protease inhibitors.
      There was no history of malignancy but two patients had past history of
      tuberculosis. The mean absolute CD4 counts were 244 cells/UL (range 103 to 392
      cells/UL) and helper CD4 counts were 19.6 cells/UL (range 15 to 30 cells/UL). All
      were anticoagulated with warfarin or enoxaparin. There was complete resolution of
      deep vein thrombosis only in one patient on long-term anticoagulation but there
      was no resolution of thrombosis in the other four patients despite of therapeutic
      anticoagulation for more than 6 months. All the patients are alive and on regular
      follow-up. Thrombosis in HIV patients is seen more commonly in middle aged,
      community ambulant male patients. The most common hypercoagulable state was noted
      as deficiency of protein S and hyperhomocysteinemia. Eighty percent of the
      patients did not respond to therapeutic anticoagulation. 

PMID- 24436594
TI  - Acute limb ischemia: surgical thromboembolectomy and the clinical course of
      arterial revascularization at ankle.
AB  - Surgical thromboembolectomy for acute limb ischemia using Fogarty catheter is
      basically a blind procedure. Therefore, the complete removal of thromboemboli in
      all calf arteries is difficult even if completion angiography or radiological
      intervention is performed. The purpose of this study is to identify whether limb
      salvage could be achieved if at least one ankle artery was revascularized by
      surgical thromboembolectomy. We also observed the effectiveness of below-knee
      popliteal approach. Over 1 year, surgical thromboembolectomy via below-knee
      popliteal artery was performed on 18 acutely ischemic limbs in 14 consecutive
      patients. All patients were diagnosed based on clinical symptoms and computed
      tomography (CT) angiography. Surgical thromboembolectomy was terminated when a
      pulse was detected by a handheld vascular Doppler device in at least one ankle
      artery after closing the arteriotomy. Patients were observed during postoperative
      anticoagulation therapy. Of the 14 patients, 1 died and 1 underwent amputation
      due to the already necrotized lesion in the foot. After 1 week of anticoagulation
      therapy, two or more arterial pulses were detected at the ankles in all 15 limbs
      from the remaining 12 patients. During the 6 to 18 months of follow-up, all 15
      limbs were salvaged successfully. In acute limb ischemia, successful limb salvage
      could be achieved by the revascularization of at least one ankle artery by
      surgical thromboembolectomy with concomitant anticoagulation therapy. Below-knee
      popliteal approach is an effective method and is worth for further study compared
      with other approaches. 

PMID- 24436595
TI  - Clinical Significance of Conditions Presenting with ECG Changes Mimicking Acute
      Myocardial Infarction.
AB  - The electrocardiogram (ECG) is the primary tool in the diagnosis of acute
      myocardial infarction (AMI). However, other clinical conditions, both cardiac and
      noncardiac originated pathologies, may result in ECG tracing of AMI. This may
      lead to an incorrect diagnosis, exposing the patients to unnecessary tests and
      potentially harmful therapeutic procedures. The aim of this report is to increase
      the still insufficient awareness of clinicians from multiple disciplines,
      regarding the different clinical syndromes, both cardiac and noncardiac,
      associated with ECG abnormalities mimicking AMI, to avoid unjustified
      thrombolytic therapy or intervention procedures. During a 9-year period, the data
      from six patients (five females, one male; mean age, 50 years [range, 18 to 78
      years]) who were admitted to cardiac care unit (CCU) with transient ECG changes
      resembling AMI were recorded retrospectively. During this 9-year period, 5,400
      patients were hospitalized in CCU: 1,350 patients were diagnosed as ST-elevation
      myocardial infarction (STEMI) and 4,050 patients were diagnosed as non-ST
      elevation myocardial infarction (NSTEMI). Only two out of six patients had chest
      pain with ECG changes criteria suspicious of AMI. STEMI was suspected in four out
      of six patients. All patients, but one, had normal left ventricular (LV)
      function. One patient had transient LV dysfunction. All patients, but one, with
      perimyocarditis, had normal serum cardiac markers. In four out of six patients,
      who underwent coronary arteries imaging during hospitalization (by angiography or
      by CT scan), normal coronary arteries were documented. Two patients who underwent
      ambulatory cardiac CT scan imaging after being discharged from hospital
      documented patent coronary arteries (case no. 3), or some insignificant
      irregularities (case no. 4). The discharge diagnoses from CCU were as follows:
      postictal syndrome, pericarditis, hypothermia, stress-induced ("tako-tsubo")
      cardiomyopathy, anaphylactic reaction, and status of postchemotherapy. All
      patients experienced full recovery with normal ECG tracing. During the 5-year
      follow-up, all patients were alive, and cardiac morbidity was not reported. We
      conclude that both cardiac and noncardiac clinical syndromes may mimic AMI.
      Comprehensive clinical examination and profound medical history are crucial for
      making the correct diagnosis in conditions with ECG changes mimicking AMI. 

PMID- 24436596
TI  - "STOP, LOOK, and LISTEN." Hepatic Portal Venous Gas: Time for Clinical
      Assessment!
AB  - Pneumatosis intestinalis and portal venous gas are findings usually associated
      with intra-abdominal surgical catastrophes that frequently require emergent
      surgical intervention. Herein we present a case of a patient who presented in
      septic shock, with extensive portal vein gas, diffuse intestinal wall thickening,
      and atherosclerotic vascular insufficiency in the absence of pneumatosis
      intestinalis. Given his advanced age, multiple comorbidities, magnitude of the
      initial findings, and his dramatic clinical response to aggressive fluid
      resuscitation, a cognitive decision was made to continue with nonoperative
      management. The patient recovered uneventfully and was discharged home in a
      stable condition. 

PMID- 24436597
TI  - Left innominate vein aneurysm: diagnostic imaging and pitfalls.
AB  - Thoracic venous aneurysms are very rare. They may be asymptomatic and can be
      found incidentally during imaging. They are associated with few complications
      including pulmonary embolism, rupture, and venous obstruction. Accurate diagnosis
      of a mediastinal aneurysm is essential to avoid complications secondary to biopsy
      or surgical intervention. This is a rare case of left innominate vein aneurysm,
      its imaging, as well as associated imaging shortfalls. 

PMID- 24436598
TI  - Endovascular repair of a traumatic thoracic aortic injury resulting in late
      aortic dilatation.
AB  - We present an unusual complication following endovascular repair of traumatic
      thoracic aortic injury using a homemade stent-graft. Although an initial
      technical success was apparently obtained, the aorta showed remarkable dilatation
      without shortening or migration of the stent skeleton in late follow-up period.
      The possible cause of the dilatation was considered to be the expansion and
      gathering of the crimped, loosely attached, graft fabric in addition to the
      incomplete exclusion due to the insufficient landing zone and the limited radial
      force. Thus, the specific feature of stent-graft, considered to provide an
      advantage to treatment, has adversely affected the native aorta. 

PMID- 24436599
TI  - Posttraumatic versus Mycotic Dorsalis Pedis Pseudoaneurysm.
AB  - Reports of dorsalis pedis aneurysms are rare, and there are currently no reports
      of mycotic dorsalis pedis aneurysms in the literature. Most dorsalis pedis
      pseudoaneurysms are diagnosed by physical exam and color flow duplex. Surgical
      treatment includes aneurysm resection with or without reconstruction of the
      dorsalis pedis artery. We report a dorsalis pedis pseudoaneurysm diagnosed
      clinically and via duplex ultrasound, treated by excision and ligation of the
      aneurysm. 

PMID- 24436600
TI  - Lemierre syndrome-should we anticoagulate? A case report and review of the
      literature.
AB  - Lemierre syndrome is an uncommon condition classically described in acute
      oropharyngeal infection with septic thrombophlebitis of the internal jugular vein
      and metastatic septic embolism particularly to the lungs. It is commonly
      described in young healthy adults with isolation of Fusobacterium necrophorum. We
      describe a case of Lemierre syndrome in a 50-year-old man with newly diagnosed
      diabetes mellitus presenting with a neck abscess secondary to Klebsiella
      pneumoniae. Our patient made good recovery to appropriate antimicrobial therapy,
      prompt surgical drainage, and anticoagulation. Anticoagulation remains
      controversial and we review the literature for its role in Lemierre syndrome. 

PMID- 24436601
TI  - Pulmonary artery aneurysms: four case reports and literature review.
AB  - Aneurysms of the pulmonary artery are proven to be a very rare entity.
      Association with structural cardiac anomalies, structural vascular anomalies,
      pulmonary hypertension, vasculitis, and infection has been noted. Surgical
      intervention of symptomatic aneurysms is recommended. A more detailed study of
      the natural history of these aneurysms is needed. Here, we report four cases of
      pulmonary artery aneurysms as well as a brief review of the literature existing
      on this subject. The first case is of a 41-year-old woman with the aneurysm
      located 1 cm distal to the pulmonary valve extending to the bifurcation of the
      main pulmonary artery. The second case is of a 76-year-old woman with a large
      aneurysm of the main pulmonary artery and the left pulmonary artery. The third
      case is of a 61-year-old woman with an aneurysm of the common pulmonary artery
      and right pulmonary artery. The fourth case is of a 28-year-old woman with a 5-cm
      symptomatic aneurysm extending from the valve up to the pulmonary bifurcation.
      Surgical excision and reconstruction was ordered for cases 1, 2, and 4. 

PMID- 24436602
TI  - Adverse reactions to iodinated contrast media.
AB  - The use of iodinated contrast agents for angiography dates back to the 1920s.
      With over 75 million contrast-requiring procedures performed annually worldwide,
      it is important to understand the risk factors, pathogenesis, diagnosis,
      prevention, and treatment of adverse reactions caused by iodinated contrast media
      (ICM). As contrast media have evolved from ionic, high-osmolality to nonionic,
      low-osmolality formulations the risk of reactions has decreased over time;
      however, no pretreatment protocol has been shown to eliminate all repeat
      reactions. Clinical alertness and early recognition of adverse reactions is of
      paramount importance and key for appropriate management of these patients. In
      this article, we review the most recent literature regarding adverse reactions to
      ICM and provide an insight into the pathogenesis, clinical presentation,
      pretreatment, and management of contrast-related reactions. 

PMID- 24436603
TI  - Accuracy of duplex ultrasonography in estimation of severity of peripheral
      vascular disease.
AB  - Duplex ultrasonography (DUS) is a safe, noninvasive method for imaging
      vasculature when compared with conventional angiography. Our goal is to assess
      the accuracy of DUS compared with angiography of the lower extremities. We
      reviewed a total of 373 lesions in 278 patients from July 2005 through June 2010.
      Patients underwent DUS followed by angiography within 30 days. Peak systolic
      velocities (PSV) were stratified into one of four categories and compared with
      the angiographic findings. Seventy-five chronic total occlusions were found. Of
      the remaining 298 lesions, a significant relationship was found between PSV and
      degree of angiographic stenosis (p < 0.001). DUS was found to demonstrate a
      sensitivity of 79.7%, specificity of 79.2%, positive predictive value of 88.2%,
      and negative predictive value of 66.7% for lesions >= 70%. The 66.7% of the false
      negative lesions with the lowest velocities were below the knee joint. DUS of the
      lower extremities is accurate in determining the degree of stenosis ranging from
      mild-to-severe disease. Some limitation may exist in estimating the degree of
      stenosis below the knee. 

PMID- 24436604
TI  - Effect of short-term low-intensity exercise training on association of oxygen
      free radicals and nitric oxide production in patients with acute myocardial
      infarction.
AB  - Moderate-to-high intensity of exercise training within 2 to 3 months decreases
      oxygen free radicals (reactive oxygen species, ROS) and increases nitric oxide
      (NO) in outpatients with myocardial infarction. There is no data about the
      association of ROS and NO after short-term low-intensity exercise training within
      5 days in patients hospitalized with acute myocardial infarction (AMI). A total
      of 32 male patients with AMI were randomized into two groups: 15 patients with
      short-term low-intensity exercise training within 5 days formed the training
      group and 17 patients without such exercise training formed the control group.
      All patients performed exercise treadmill test with modified Bruce protocol
      before and after the study. F2-isoprostane and NO concentration of the training
      group increased slightly after modified Bruce exercise treadmill test. Compared
      with the control group, NO of the training group was also slightly higher.
      Baseline NO and uric acid were negative predictor variables for F2-isoprostane in
      all patients hospitalized with AMI, and triglyceride was a positive predictor
      variable. After the study, physical capacity of the training group was higher;
      but heart rate and systolic blood pressure were lower significantly. This study
      showed that short-term low-intensity exercise training for patients hospitalized
      with AMI did not change ROS and NO productions, but it improved physical capacity
      and lowered heart rate and systolic blood pressure. NO was negative predictor
      variable for F2-isoprostane in controlling ROS changes in dynamic compensation
      mechanism. 

PMID- 24436605
TI  - Outcomes of Patients Treated with the Everolimus- versus the Paclitaxel-Eluting
      Stents in a Consecutive Cohort of Patients at a Tertiary Medical Center.
AB  - In this study, we compare the outcomes of the paclitaxel-eluting stent (PES)
      versus the everolimus-eluting stent (EES) treated patients at a tertiary medical
      center and up to 2 years follow-up. Unselected consecutive patients were
      retrospectively recruited following stenting with PES (159 patients) or EES (189
      patients). The primary endpoint of the study was target lesion failure (TLF),
      defined as the combined endpoint of cardiac death, nonfatal myocardial infarction
      (MI), or target lesion revascularization (TLR). Secondary endpoints included
      target vessel revascularization (TVR), TLR, target vessel failure (TVF), acute
      stent thrombosis (ST), total death, cardiac death, and nonfatal MI. Patients
      treated with the PES stent had less congestive heart failure and restenotic
      lesions, but a higher prevalence of longer lesions, nonleft main bifurcations,
      required more stents per patient (4.3 +/- 2.8 vs. 2.9 +/- 2.1). TLF occurred in
      32.3% PES versus 21.5% EES (p = 0.027). The secondary unadjusted endpoints for
      PES versus EES, respectively, were TVF 38.6 versus 30.7% (p = 0.140), TVR 35.7
      versus 26.5% (p = 0.079), definite and probable ST 1.2 versus 0.0%, nonfatal MI
      4.5 versus 4.2%, and mortality 9.6 versus 4.0%. Logistic regression analysis
      showed that the numbers of stents per patient (p = 0.001), age (p = 0.01), and
      renal failure (p = 0.045) were independent predictors of TLF. Using univariate
      analysis, EES had lower TLF than PES in a cohort of unselected patients
      undergoing percutaneous coronary intervention at 2 years follow-up. Multivariate
      analysis showed that the numbers of stents per patient, age, and renal failure,
      but not stent type, were predictors of TLF. 

PMID- 24436606
TI  - Association of heart block with uncommon disease States.
AB  - A variety of diseases, other than the common Lev-Lenegre disease, are associated
      with cardiac conduction system abnormalities. These include acute processes, such
      as acute rheumatic fever, and other disorders, such as sarcoidosis, connective
      tissue disorders, neoplasms, and bacterial endocarditis with cardiac abscess
      formation. The purpose of the study is to raise awareness of these rare
      conditions. We present 10 adult patients (4 males and 6 females) with a mean age
      of 47 years (range: 19-69), with various rare diseases associated with heart
      block, who needed temporary or permanent pacemaker therapy in the past two
      decades. These conditions included acute rheumatic carditis, Wegener
      granulomatosis, cardiac involvement of metastatic breast cancer, bacterial
      endocarditis, sarcoidosis, S/P chest radiotherapy, and quadriplegia with
      syringomyelia postspinal cord injury, and adult congenital heart block. We
      conclude that patients with these disorders should be followed periodically, to
      allow for early detection and treatment of cardiac conduction disturbances, with
      pacemaker therapy. 

PMID- 24436607
TI  - Intercoronary continuity: a case report.
AB  - Intercoronary continuity is a rare variance of coronary circulation. The
      importance of this rare anomaly is unknown. We present this rare anomaly in a
      patient with acute myocardial infarction. 

PMID- 24436608
TI  - Thrombus Entrapment in the Hemostasis Valve during Thrombus Aspiration: An
      Octogenarian with Inferior Myocardial Infarction and Complete Flow Restoration
      without Any Additional Angioplasty.
AB  - Published reports demonstrate improved myocardial reperfusion with adjunctive
      thrombus aspiration in ST-elevation myocardial infarction (STEMI). However,
      implementation of this procedure without angioplasty or stent implantation is not
      clear. In this report, we present an octogenarian with inferior STEMI who was
      treated with thrombus aspiration alone. Another important feature of our case is
      trapped thrombus material in the guiding catheter during thrombus aspiration.
      Operators should avoid thrombus re-injection by controlling the system carefully
      during aspiration procedure. 

PMID- 24436609
TI  - Retrieval of Broken Export Catheter during Primary Angioplasty.
AB  - Broken catheter fragments in a coronary artery during percutaneous coronary
      interventions although uncommon can potentially result in life-threatening
      consequences from the attended embolization, thrombus formation, and perforation.
      We report an unusual complication of a broken export catheter during primary
      angioplasty, which was successfully managed by inflated balloon-mediated
      retrieval technique. 

PMID- 24436610
TI  - Diagnosis of coronary artery fistulas: clinical aspects and brief review of the
      literature.
AB  - An 86-year-old woman with history of hypertension, diabetes, hyperlipidemia, and
      coronary artery disease was admitted with new-onset congestive heart failure and
      pneumonia. She underwent coronary angiography after suffering a non-ST elevation
      myocardial infarction. There was severe coronary artery disease in addition to
      coronary artery-pulmonary fistulas involving proximal right coronary artery and a
      branch of left main coronary artery. Coronary artery fistula (CAF) is an abnormal
      communication between one or more coronary arteries and great vessels or a
      cardiac chamber. We reviewed 15 cases of CAFs published in PubMed and studied the
      clinical features of CAFs. 

PMID- 24436611
TI  - A rare case of behcet disease presenting with pyrexia of unknown origin,
      pulmonary embolism, and right ventricular thrombus.
AB  - Behcet disease is a systemic vasculitis characterized by recurrent oral and
      genital ulcers and uveitis. We describe a rare case of a 43-year-old woman with
      Behcet disease who was admitted for pyrexia of unknown origin, cough, dyspnea,
      and chest pain. Her computerized tomography scan revealed pulmonary embolism and
      right ventricular thrombus. She was treated with anticoagulation for pulmonary
      embolism and right ventricular thrombus. She was well during her last follow-up. 

PMID- 24436612
TI  - Coronary sinus ostial atresia and persistent left-sided superior vena cava:
      clinical significance and strategies for cardiac resynchronization therapy.
AB  - A 48-year-old male patient underwent cardiac resynchronization therapy
      defibrillator implantation, and he was found to have atresia of the coronary
      sinus ostium with venous drainage occurring via a persistent left-sided superior
      vena cava, which was connected to the right-sided superior vena cava by the
      innominate vein. This is a rare benign cardiac anomaly that can pose problems
      when the coronary sinus needs to be cannulated. To identify the course of the
      coronary sinus, a coronary angiogram can be performed with attention directed to
      the venous phase of the angiogram. Although the technical difficulty of coronary
      sinus cannulation increases, various catheters, wires, and delivery systems can
      be utilized and this anomaly does not usually prevent successful left ventricular
      lead placement in cardiac resynchronization therapy via a left-sided superior
      vena cava approach. There however needs to be consideration regarding caliber of
      the left-sided superior vena cava being sufficiently large to avoid compromise of
      venous drainage after lead insertion. 

PMID- 24436613
TI  - Rotational Atherectomy in a Patient with Acute ST-Elevation Myocardial Infarction
      and Cardiogenic Shock.
AB  - Rotational atherectomy (rotablation) of coronary artery is relatively
      contraindicated in high thrombotic state such as acute ST-elevation myocardial
      infarction (STEMI) because of the risk of platelet activation by the rotablator.
      We present a case where rotablation was necessary to recanalize the right
      coronary artery in a patient presenting with acute STEMI complicated by
      cardiogenic shock, after unsuccessful attempts with balloon catheters. He
      improved remarkably after the procedure and was discharged after 4 days. 

PMID- 24436614
TI  - Percutaneous Hemodynamic Support (Impella) in Patients with Advanced Heart
      Failure and/or Cardiogenic Shock Not Eligible to PROTECT II Trial.
AB  - PROTECT I and II trials have tested the efficacy of Impella in patents with high
      risk percutaneous coronary intervention (PCI). However, patients with severe
      hemodynamic instability such as cardiac arrest, ST-segment elevated myocardial
      infarction (STEMI), or cardiogenic shock were excluded. The objective was to
      investigate the efficacy of Impella in sicker patient population who were not
      included in PROTECT trials. These patients merit high-risk PCI who had
      cardiogenic shock and unstable or decompensated heart failure (HF). From December
      2010 to March 2012, 10 consecutive patients with extremely high surgical risk and
      hemodynamic instability underwent urgent PCI with Impella 2.5 support (Abiomed
      Inc., Danvers, MA). These patients were presented with advance HF and/or
      cardiogenic shock. Among the 10 included patients, 3 patients were with cardiac
      arrest and 1 patient was with acute myocardial infarction. All patients had
      successful Impella implantation and remained hemodynamically stable during high
      risk PCI. Among the 10 patients 2 patients (20%) died within 1 month and 1
      patient developed limb ischemia. In high-risk population nonrandomizable to
      PROTECT trials with advance HF/cardiogenic shock, Impella could be an important
      tool for hemodynamic support to PCI or could be a bridge to left ventricle assist
      device to achieve good recovery. Larger studies need to be conducted on this high
      risk population. 

PMID- 24436615
TI  - The Use of Intra-aortic Balloon Pump in a Real-World Setting: A Comparison
      between Survivors and Nonsurvivors from Acute Coronary Syndrome Treated with
      IABP. The Jakarta Acute Coronary Syndrome Registry.
AB  - Real-world data on acute coronary syndrome (ACS) patients who received intra
      aortic balloon pump (IABP) support are limited. The objective of this study was
      to evaluate the characteristics of ACS patients who received IABP support from a
      real-world ACS registry. Patients with ACS (N = 121) who received IABP support
      were enrolled. Characteristics of survivors and nonsurvivors were compared at 30
      days. Mortality rate of patients with ACS who received IABP was 47%. The
      survivors (N = 64) had less often cardiogenic shock (p < 0.001), more often IABP
      usage as back-up for a revascularization procedure (p = 0.002), less often
      resuscitation (p = 0.043), and less mechanical ventilator support (p < 0.001)
      than nonsurvivors. The nonsurvivors had a significantly higher leukocyte count (p
      = 0.033), a higher serum creatinine level (p < 0.001), a higher blood sugar on
      admission (p = 0.001), higher creatine kinase MB levels (p = 0.002), and a higher
      serum uric acid level (p < 0.001), but significantly lower left and right
      ventricular function (p = 0.014 and p = 0.003, respectively) than survivors. At
      30 days, non-ST elevation (STE)-ACS patients had lower mortality rate than ST
      segment elevation myocardial infarction patients (log-rank test, p < 0.001), and
      non-STE-ACS patients who had not suffered from cardiogenic shock showed the
      lowest mortality rate (log-rank test, p < 0.001). By multivariate analysis, a
      heart rate >= 100 beats per minute before IABP insertion was the strongest
      predictor of 30-day mortality (hazard ratio = 5.69; 95% confidence interval, 1.49
      to 21.78; p = 0.011). In ACS patients presenting with either cardiogenic shock,
      resuscitated, or patients who needed mechanical ventilation suffered from high
      mortality, despite the use of IABP. IABP appears to be safe and tended to be
      favorable in noncardiogenic shock ACS patients, particularly non-STE-ACS. A heart
      rate of >= 100 beats per minute prior to IABP insertion was the strongest
      predictor of 30-day mortality. 

PMID- 24436616
TI  - Determinants of left ventricular hypertrophy in hypertensive patients:
      identification of high-risk patients by metabolic, vascular, and inflammatory
      risk factors.
AB  - Left ventricular hypertrophy (LVH) is recognized as an independent predictor of
      cardiovascular morbidity and mortality in hypertensive patients. Thus, it is
      critical to understand the mechanisms underlying the development of LVH for
      formulation screening and treatment strategies. This study was designed to
      determine the association between echographically determined LVH measures and
      markers of inflammation, neurohormonal activity, glomerular function, oxidative
      stress, insulin resistance, and vascular endothelial function. In this study, 129
      hypertensive subjects were evaluated for lipids, glucose, HbA1C, insulin,
      homeostasis model assessment-insulin resistance, C-reactive protein (CRP),
      urinary microalbumin, homocysteine, aldosterone, renin, and endothelin. LVH
      parameters including interventricular septum thickness, posterior wall thickness
      (PWT), and left ventricular mass index (LVMI) were assessed echographically.
      Serum aldosterone levels were significantly positively associated with left
      ventricular mass (LVM) and marginally positively associated with LVMI and PWT.
      Both LVM and LVMI were significantly elevated in subjects with high versus normal
      serum aldosterone levels (p = 0.018 for LVM and p = 0.050 for LVMI). Serum
      endothelin was positively associated with LVM and LVMI. In multiple linear
      regression analysis, aldosterone remained a significant predictor of LVM
      (standardized beta = 0.229, p = 0.024), and endothelin a marginally significant
      predictor of LVM (standardized beta = 0.178, p = 0.077). Among serum lipids, high
      density lipoprotein cholesterol only had a significant inverse association with
      LVM and PWT. Homocysteine as well as CRP were significantly positively associated
      with LVM and LVMI in females. This study found that aldosterone and endothelin
      levels are the most important independent determinants of LVH in hypertensive
      subjects. These markers may be useful to identify asymptomatic hypertensive
      subjects at risk for heart failure. 

PMID- 24436617
TI  - Prevalence and predictors of left ventricular diastolic dysfunction in a Hispanic
      patient population.
AB  - Minimal data exist on attributes of diastolic dysfunction in the Hispanic
      population. The purpose of this study was to evaluate the prevalence and
      predictors of diastolic dysfunction in a Hispanic patient population. We
      performed a retrospective review of 166 consecutive echocardiograms in a
      southwestern Texas Hospital that caters to a large Hispanic patient population.
      We identified all echocardiograms that met criteria for diastolic dysfunction and
      assessed baseline demographics and comorbidities in the cohort of Hispanic
      patients. A multivariate analysis was performed to identify the independent
      predictors of diastolic dysfunction. A total of 129 out of 166 patients (77.8%)
      were of Hispanic origin. Out of the 129 patients, 87 (67.4%) had some degree of
      diastolic dysfunction in this population suggesting a high prevalence in the
      study cohort. In the diastolic dysfunction group, the mean age was 64.5 +/- 13.9,
      37% were male and 63% female, 78% had diabetes, 85% had hypertension, and 49% had
      some degree of renal insufficiency (stages 3-5). A logistic multivariate analysis
      showed that diabetes was an independent predictor of diastolic dysfunction with
      odds ratio of 2.69 (95% confidence interval [CI], 1.06-6.28; p = 0.038).
      Similarly age (per year increase) and chronic kidney disease were independent
      predictors of diastolic dysfunction. We demonstrated that older age, presence of
      diabetes, and renal dysfunction are independent predictors of diastolic
      dysfunction in the Hispanic patient population. Strategies geared toward reducing
      diabetes and preventing renal dysfunction are likely to decrease prevalence of
      diastolic dysfunction and heart failure in this community. 

PMID- 24436618
TI  - Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to
      ACE Inhibitors in the Treatment of Hypertension.
AB  - Secoisolariciresionol diglucoside (SDG) is a plant lignan isolated from flaxseed
      and is phytoestrogen. SDG is a potent and long-acting hypotensive agent. Plant
      phytoestrogens have inhibitory effects on angiotensin-converting enzyme (ACE).
      The hypotensive effects of SDG, a phytoestrogen, may be mediated through
      inhibition of ACE. The objective of this study was to investigate if SDG-induced
      hypotension is mediated through inhibition of ACE. The Sprague Dawley male rats
      were anesthetized and trachea was cannulated. The right jugular vein was
      cannulated to administer the drug and the carotid artery was cannulated to record
      arterial pressures using PIOEZ-1 miniature model transducer (Becton, Dickinson
      and Company, Franklin Lakes, NJ) and Beckman dynograph (Beckman Instruments,
      Inc., Schiller Park, IL). The effects of angiotensin I (0.2 ug/kg, intravenously
      [IV]) in the absence and presence of SDG (10 mg/kg, IV), and SDG alone on
      systolic, diastolic, and mean arterial pressures were measured before and after
      15, 30, and 60 minutes of drug administration. SDG decreased the systolic,
      diastolic, and mean arterial pressure by 37, 47, and 43%, respectively, at 15
      minutes and 18.8, 21.2, and 20.3%, respectively, at 60 minutes. Angiotensin I
      increased the arterial pressure. SDG decreased angiotensin I-induced rise in the
      systolic, diastolic, and mean arterial pressures by 60, 58, and 51%,
      respectively, at 15 minutes and 48, 46, and 30%, respectively, at 60 minutes. The
      data suggest that SDG reduced the angiotensin I-induced rise in the arterial
      pressures and hence SDG is a potent ACE inhibitor. 

PMID- 24436619
TI  - Coronary Artery Perforation following PCI: An Interesting Finding into the
      Pericardial Space.
AB  - Coronary artery perforation is a known complication of percutaneous coronary
      intervention and potentially life threatening. Normally, these perforations are
      small and localized. We report the successful surgical management of a coronary
      artery perforation following stent insertion with extrusion of an 8-cm
      endarterectomy length of the circumflex coronary artery with a brief review of
      the recent literature. 

PMID- 24436620
TI  - Repair of vascular ring with resection of kommerell diverticulum and
      transposition of aberrant left subclavian artery.
AB  - A 32-year-old female presented with dysphagia. Radiographic studies revealed
      external compression of esophagus by a vascular ring. The anatomy was a right
      sided aortic arch with aberrant retroesophageal left subclavian artery, emanating
      from a large Kommerell diverticulum (KD). Traditional repair with ligamentum
      division and adhesiolysis leaves a large KD still adjacent to the esophagus with
      the potential for persistent or recurrent symptoms. The objective of this study
      was the modification of operative technique to minimize the potential for
      persistent or recurrent symptoms. The operative repair included resection of KD
      with transposition of the left subclavian artery into the left carotid artery, in
      addition to the division of the ligamentum arteriosum and mobilization of the
      esophagus. The patient's dysphagia resolved and postoperative barium studies
      showed no residual compression. There were no significant perioperative
      complications. Resection of KD is a potential adjunct to traditional repair of
      vascular rings and might offer better long-term palliation by minimizing residual
      vascular compression of the esophagus. 

PMID- 24436621
TI  - Rare case of "wandering artery of drummond" as a result of chronic triple
      mesenteric vessel occlusion treated by isolated angioplasty and stenting of the
      inferior mesenteric artery.
AB  - We report a rare clinical scenario of chronic mesenteric ischemia (CMI) patient
      with obstruction of all the three major gut vessels including celiac, superior
      mesenteric artery (SMA), and inferior mesenteric artery (IMA) with a sole artery
      supplying the collaterals through marginal artery of left colon (the "wandering
      artery of Drummond"). A 70-year-old man was presented to hospital with acute
      onset of dyspnea, diaphoresis, severe epigastric pain, nausea, and vomiting that
      started after lunch. Initially, patient was diagnosed and treated for non-ST
      elevation myocardial infarction (NSTEMI). Furthermore, work-up, including
      computed tomographic scan of abdomen followed by angiogram, revealed 100%
      obstruction of celiac and SMA, whereas inferior IMA had 90% ostial lesion with
      poststenotic dilatation and collaterals supplying to entire colon. Subsequently,
      IMA ostial lesion was stented through percutaneous intervention and patient noted
      significantly improved symptoms and quality of life. To conclude, percutaneous
      endovascular treatments confer favorable strategy for CMI, and it may either be
      curative or allow nutritional optimization before definitive surgery. 

PMID- 24436622
TI  - Spontaneous coronary artery dissection in a young man with a factor v leiden gene
      mutation: a case report and review of the literature.
AB  - Spontaneous coronary artery dissection is a rare but increasingly recognized
      cause of acute myocardial ischemia in young adults, especially in women. We
      report a case of spontaneous coronary dissection in a young healthy man who was
      also a carrier of the factor V Leiden gene mutation. 

PMID- 24436623
TI  - A Rare Case of Acute Pulmonary Embolism after Coronary Angiography due to Sand
      Bag Compression.
AB  - Pulmonary embolism (PE) is very rare after coronary angiography. We present here
      a case of acute PE after coronary angiography due to sand bag compression which
      has not been reported previously. After the femoral sheath removal, patient was
      immobilized for 6 hours with a sand bag on his right femoral artery area. After
      the removal of sand bag, patient stood up with the help of a nurse. Immediately
      after standing up, patient complained sudden onset of dyspnea, lost his
      consciousness, and suddenly fell on the ground while hitting left occipital
      region of his head. Clinical, echocardiographic, laboratory, and tomographic
      findings were compatible with massive PE and we decided to give thrombolytic
      agent. On the contrary, because he had cranial trauma during syncope and oozing
      type hemorrhage in his right inguinal region, we administered a total dose of 50
      mg alteplase (tissue plasminogen activator) within 2 hours (normal recommended
      dose is 100 mg). Just after finishing alteplase, clinical, laboratory, and
      echocardiographic parameters of the patient returned to normal without any
      complication. Patient was discharged with warfarin treatment 5 days after the
      event. 

PMID- 24436624
TI  - Ileocolic to right iliac arterial transposition for the treatment of chronic
      mesenteric ischemia.
AB  - The treatment of chronic mesenteric ischemia remains challenging and controversy
      exists over the best interventional option. Endovascular treatment has emerged as
      first-line management due to its associated lower morbidity and mortality than
      surgical reconstruction. However, open mesenteric reconstructions continue to
      play an important role in patients with lesions that are unsuitable for an
      endovascular option. Mesenteric operations utilize the aorta or iliac artery as
      the inflow source for a vein or prosthetic bypass to the celiac artery or
      superior mesenteric artery. We describe an exceptional case of chronic mesenteric
      ischemia due to atherosclerosis that was treated successfully with a novel
      ileocolic to right iliac arterial transposition. 

PMID- 24436625
TI  - A case of aortic regurgitation and hypotension.
AB  - Takayasu arteritis is a chronic inflammatory large vessel vasculitis affecting
      the aorta and its main branches. It can present in various forms, and thereby may
      lead to a delay in diagnosis. We present a patient with Takayasu arteritis,
      diagnosed at our center when she presented with severe aortic regurgitation. We
      also review the current knowledge base with respect to Takayasu arteritis. 

PMID- 24436626
TI  - Edaravone Suppresses Reperfusion Injury following Leg Ischemia in Rats: A
      Transmission Electron Microscopic Study.
AB  - It is well known that free radicals cause reperfusion injury following leg
      ischemia. We showed that the free radical scavenger, edaravone (Radicut,
      Mitsubishi Tanabe Pharma Co., Osaka, Japan), might suppress reperfusion injury in
      rat. In this study, we used transmission electron microscope (TEM) to investigate
      how edaravone suppresses reperfusion injury by focusing on glycogen granules in
      the lower extremity muscles. Male Lewis rats (582 +/- 35 g) were
      intraperitoneally injected with edaravone (3.0 mg/kg, edaravone group, n = 5) or
      the same dose of saline (control group, n = 5). The rat reperfusion injury models
      were induced by clamping the bilateral common femoral arteries for 5 hours and
      then declamping. The muscles were harvested at 5 hours after the start of
      reperfusion. Under a TEM (JEM-1220, Nippon Denshi Co., Tokyo, Japan), we counted
      the number of glycogen granules at *50,000 magnification on each five different
      fields. The TEM sections from the control group showed a marked loss of glycogen
      granules and swollen mitochondria. In contrast, the TEM sections from the
      edaravone group showed numerous glycogen granules and normal mitochondria. The
      mean density of glycogen granules in the edaravone group was significantly higher
      than that in the control group (88.5 +/- 5.3 vs. 16.4 +/- 3.1 particles/um(2), p
      < 0.001). Our TEM results confirmed that edaravone suppresses reperfusion injury
      following leg ischemia by maintaining the glycogen granules in muscles. 

PMID- 24436627
TI  - Training and Maintaining System-Wide Reliability in Outcome Management.
AB  - The Child and Adolescent Functional Assessment Scale (CAFAS) is widely used for
      outcome management, for providing real time client and program level data, and
      the monitoring of evidence-based practices. Methods of reliability training and
      the assessment of rater drift are critical for service decision-making within
      organizations and systems of care. We assessed two approaches for CAFAS training:
      external technical assistance and internal technical assistance. To this end, we
      sampled 315 practitioners trained by external technical assistance approach from
      2,344 Ontario practitioners who had achieved reliability on the CAFAS. To assess
      the internal technical assistance approach as a reliable alternative training
      method, 140 practitioners trained internally were selected from the same pool of
      certified raters. Reliabilities were high for both practitioners trained by
      external technical assistance and internal technical assistance approaches (.909
      .995, .915-.997, respectively). 1 and 3-year estimates showed some drift on
      several scales. High and consistent reliabilities over time and training method
      has implications for CAFAS training of behavioral health care practitioners, and
      the maintenance of CAFAS as a global outcome management tool in systems of care.

PMID- 24436628
TI  - Bark frequency transform using an arbitrary order allpass filter.
AB  - We propose an arbitrary order stable allpass filter structure for frequency
      transformation from Hertz to Bark scale. According to the proposed filter
      structure, the first order allpass filter is causal, but the second and higher
      order allpass filters are non-causal. We find that the accuracy of the
      transformation significantly improves when a second or higher order allpass
      filter is designed compared to a first order allpass filter. We also find that
      the RMS error of the transformation monotonically decreases by increasing the
      order of the allpass filter.

PMID- 24436629
TI  - Geomagnetic and Geoelectric Prospection on a Roman Iron Production Facility in
      Huttenberg, Austria (Ferrum Noricum).
AB  - Geophysical prospection has been applied in the Huttenberg area (Carinthia,
      Austria), where important parts of the Roman iron production in the province of
      Noricum between the first century bc and the fourth century ad are located. A
      combination of geomagnetic, geoelectric and electromagnetic measurements at
      different scales yielded information about the extent of the industrial complex
      and the location of yet undiscovered subsurface monuments in the surrounding area
      of the Semlach-Eisner archaeological site. The vertical and lateral extension of
      a slag deposit from the smelting activities could be determined by means of
      geomagnetic mapping and multi-electrode geoelectric profiles. For the prediction
      of the continuation of walls in the subsurface outside the excavated area, the
      total horizontal derivative of the magnetic anomaly as well as geoelectric
      measurements were most suitable, whereas electromagnetic measurements were not
      successful owing to the high conductivity of widely spread pieces of slag.
      Copyright (c) 2011 John Wiley & Sons, Ltd.

PMID- 24436630
TI  - Infection Prevention Research in Nursing Homes.

PMID- 24436631
TI  - Differences in intergenerational fertility associations by sex and race in Saba,
      Dutch Caribbean, 1876-2004.
AB  - This study examines the intergenerational transmission of fertility behavior in
      Saba, Dutch Caribbean from 1876 to 2004 using reconstituted genealogies. Pearson
      product-moment correlation coefficients of several fertility measures and event
      history models of age at first birth are used to explore relationships between
      the fertility of mothers and their children. The strength of intergenerational
      fertility ties varies by race and gender. Individuals that are better positioned
      to realize their fertility preferences have the strongest intergenerational
      associations, while individuals with the most limited reproductive options have
      the weakest intergenerational associations. This evidence supports hypotheses
      that posit the intergenerational transmission of attitudes, goals, and behaviors
      and the ability to act on those preferences as drivers of the presence or
      magnitude of links between the fertility of parents and their children.

PMID- 24436632
TI  - The Physical Economy of the United States of America.
AB  - The United States is not only the world's largest economy, but it is also one of
      the world's largest consumers of natural resources. The country, which is
      inhabited by some 5% of the world's population, uses roughly one-fifth of the
      global primary energy supply and 15% of all extracted materials. This article
      explores long-term trends and patterns of material use in the United States.
      Based on a material flow account (MFA) that is fully consistent with current
      standards of economy-wide MFAs and covers domestic extraction, imports, and
      exports of materials for a 135-year period, we investigated the evolution of the
      U.S. industrial metabolism. This process was characterized by an 18-fold increase
      in material consumption, a multiplication of material use per capita, and a shift
      from renewable biomass toward mineral and fossil resources. In spite of
      considerable improvements in material intensity, no dematerialization has
      happened so far; in contrast to other high-income countries, material use has not
      stabilized since the 1970s, but has continued to grow. This article compares
      patterns and trends of material use in the United States with those in Japan and
      the United Kingdom and discusses the factors underlying the disproportionately
      high level of U.S. per capita resource consumption.

PMID- 24436633
TI  - Thermodynamic and Differential Entropy under a Change of Variables.
AB  - The differential Shannon entropy of information theory can change under a change
      of variables (coordinates), but the thermodynamic entropy of a physical system
      must be invariant under such a change. This difference is puzzling, because the
      Shannon and Gibbs entropies have the same functional form. We show that a
      canonical change of variables can, indeed, alter the spatial component of the
      thermodynamic entropy just as it alters the differential Shannon entropy.
      However, there is also a momentum part of the entropy, which turns out to undergo
      an equal and opposite change when the coordinates are transformed, so that the
      total thermodynamic entropy remains invariant. We furthermore show how one may
      correctly write the change in total entropy for an isothermal physical process in
      any set of spatial coordinates.

PMID- 24436634
TI  - T Cell Transcription Factors and Their Impact on HIV Expression.
AB  - By targeting CD4+ effector T cells, HIV has a dramatic impact on the depletion,
      expansion and function of the different polarized T cell subsets. The maturation
      of T cell lineages is in part driven by intrinsic transcription factors that
      potentially influence how efficiently HIV replicates. In this review, we explore
      whether transcription factors that are required for polarizing T cells influence
      HIV replication. In particular, we examine provirus transcription as well as the
      establishment and maintenance of HIV latency. Furthermore, it is suggested these
      factors may provide novel cell-specific therapeutic strategies for targeting the
      HIV latent reservoir.

PMID- 24436635
TI  - Directing driver attention with augmented reality cues.
AB  - This simulator study evaluated the effects of augmented reality (AR) cues
      designed to direct the attention of experienced drivers to roadside hazards.
      Twenty-seven healthy middle-aged licensed drivers with a range of attention
      capacity participated in a 54 mile (1.5 hour) drive in an interactive fixed-base
      driving simulator. Each participant received AR cues to potential roadside
      hazards in six simulated straight (9 mile long) rural roadway segments. Drivers
      were evaluated on response time for detecting a potentially hazardous event,
      detection accuracy for target (hazard) and non-target objects, and headway with
      respect to the hazards. Results showed no negative outcomes associated with
      interference. AR cues did not impair perception of non-target objects, including
      for drivers with lower attentional capacity. Results showed near significant
      response time benefits for AR cued hazards. AR cueing increased response rate for
      detecting pedestrians and warning signs but not vehicles. AR system false alarms
      and misses did not impair driver responses to potential hazards.

PMID- 24436636
TI  - The genetics of progressive hearing loss: a link between hearing impairment and
      dysfunction of mechanosensory hair cells.

PMID- 24436637
TI  - Right and Righteous: Children's Incipient Understanding and Evaluation of True
      and False Statements.
AB  - Two studies examined young children's early understanding and evaluation of truth
      telling and lying, and the role that factuality plays in their judgments. Study 1
      (104 2- to 5-year-olds) found that even the youngest children reliably accepted
      true statements and rejected false statements, and that older children's ability
      to label true and false statements as "truth" and "lie" emerged in tandem with
      their positive evaluation of true statements and "truth" and their negative
      evaluation of false statements and "lie." The findings suggest that children's
      early preference for factuality develops into a conception of "truth" and "lie"
      that is linked both to factuality and moral evaluation. Study 2 (128 3- to 5-year
      olds) found that, whereas young children exhibited good understanding of the
      association of true and false statements with "truth," "lie," "mistake," "right,"
      and "wrong," they showed little awareness of assumptions about speaker knowledge
      underlying "lie" and "mistake." The results further support the primacy of
      factuality in children's early understanding and evaluation of truth and lies.

PMID- 24436638
TI  - Elicited Imitation Performance at 20 Months Predicts Memory Abilities in School
      Age Children.
AB  - Over the first decade of life there are marked improvements in mnemonic
      abilities. An important question from both a theoretical and applied perspective
      is the extent of continuity in the nature of memory over this period. The present
      longitudinal investigation examined declarative memory during the transition from
      toddlerhood to school-age using both experimental and standardized assessments.
      Results indicate significant associations between immediate nonverbal recall at
      20 months (measured by elicited imitation) and immediate verbal and nonverbal
      memory (measured by standardized and laboratory-based tasks) at 6 years in
      typically developing children. Regression models revealed this association was
      specific, as measures of language abilities and temperament were not predictive
      of later memory performance. These findings suggest both continuity and
      specificity within the declarative memory system over the first years of life.
      Theoretical and applied implications of these findings are discussed.

PMID- 24436640
TI  - Technology and health information in colorectal surgery.

PMID- 24436639
TI  - Scott R. Steele, MD.

PMID- 24436641
TI  - Working with existing databases.
AB  - Outcomes research has established itself as an integral part of surgical research
      as physicians and hospitals are increasingly required to demonstrate attainment
      of performance markers and surgical safety indicators. Large-volume and clinical
      and administrative databases are used to study regional practice pattern
      variations, health care disparities, and resource utilization. Understanding the
      unique strengths and limitations of these large databases is critical to
      performing quality surgical outcomes research. In the current work, we review the
      currently available large-volume databases including selection processes, modes
      of analyses, data application, and limitations. 

PMID- 24436642
TI  - Working with industry: what is the conflict?
AB  - The relationship between medicine and industry has always shared conflicts. There
      are obvious benefits to these relationships and inherent potential risks. The
      collaboration between academic medicine and industry has allowed for great
      advances in medicine in terms of drug, technology, and procedural developments.
      However, for-profit companies' interests may not align with those of academic
      universities. Companies tend to undertake research when the results of such work
      leads to company profits or enhances their reputation, and not solely for greater
      scientific understanding. In this article, the author reviews the types of
      conflicts of interest, the role of industry-sponsored trials, the adoption of new
      technologies from industry, and the role of industry with our medical society. 

PMID- 24436643
TI  - Electronic medical records in colorectal surgery.
AB  - Electronic medical records (EMRs) are being widely implemented today, either as
      stand-alone applications in smaller practices or as systems-based integrated
      network solutions in larger health care organizations. Advantages include rapid
      accessibility, worldwide availability, ease of storage, and secure transfer of
      protected health information (PHI). Computerized physician order entry (CPOE) and
      decision-support capabilities such as the triggering of an alarm when multiple
      medications with known interactions are ordered, as well as the seemingly endless
      possibilities for electronic integration and extraction of PHI for clinical and
      research purposes, have created opportunities and pitfalls alike. Risks include
      breaches of confidentiality with a need to implement tighter measures for
      electronic security. These measures contrast efforts required for the realization
      of common data formats that have national and even international compatibility.
      EMRs provide a common platform that could potentially allow for the integration
      and administration of clinical care, research, and quality metrics, thus
      promoting optimal outcomes for patients. Technical and medicolegal difficulties
      need to be overcome in the years to come so that the safe use of PHI can be
      ensured while still maintaining the benefits and convenience of modern EMR
      systems. 

PMID- 24436645
TI  - Technology and health information technology in colorectal surgery: electronic
      literature support.
AB  - The advent of the Internet has revolutionized the management of reporting and
      accessing research and data. The authors review the current resources available
      to surgeons through websites, accumulated published data repositories, and
      libraries. The change in how we publish and present peer-reviewed data over the
      last 20 years is also discussed as well as the future of health information
      technology. 

PMID- 24436644
TI  - Clinical decision support for colon and rectal surgery: an overview.
AB  - Clinical decision support (CDS) has been shown to improve clinical processes,
      promote patient safety, and reduce costs in healthcare settings, and it is now a
      requirement for clinicians as part of the Meaningful Use Regulation. However,
      most evidence for CDS has been evaluated primarily in internal medicine care
      settings, and colon and rectal surgery (CRS) has unique needs with CDS that are
      not frequently described in the literature. The authors reviewed published
      literature in informatics and medical journals, combined with expert opinion to
      define CDS, describe the evidence for CDS, outline the implementation process for
      CDS, and present applications of CDS in CRS.CDS functionalities such as order
      sets, documentation templates, and order facilitation aids are most often
      described in the literature and most likely to be beneficial in CRS. Further
      research is necessary to identify and better evaluate additional CDS systems in
      the setting of CRS. 

PMID- 24436646
TI  - Social media and the surgeon.
AB  - As the Internet has matured, social media has developed and become a part of our
      everyday life. Whether it is Facebook, YouTube, or LinkedIn, we now communicate
      with each other and the world in a very different manner. As physicians, and
      specifically colon and rectal surgeons, it is important that we understand this
      new technology, learn its limitations, and utilize it to foster growth of our
      practice, trade, and potentially result in better patient care. 

PMID- 24436647
TI  - Use of robotics in colon and rectal surgery.
AB  - The pace of innovation in the field of surgery continues to accelerate. As new
      technologies are developed in combination with industry and clinicians,
      specialized patient care improves. In the field of colon and rectal surgery,
      robotic systems offer clinicians many alternative ways to care for patients. From
      having the ability to round remotely to improved visualization and dissection in
      the operating room, robotic assistance can greatly benefit clinical outcomes.
      Although the field of robotics in surgery is still in its infancy, many groups
      are actively investigating technologies that will assist clinicians in caring for
      their patients. As these technologies evolve, surgeons will continue to find new
      and innovative ways to utilize the systems for improved patient care and comfort.

PMID- 24436650
TI  - Brian R. Kann, MD, FACS, FASCRS.

PMID- 24436648
TI  - Simulation and its role in training.
AB  - Despite its short history, surgical simulation has been successfully introduced
      into surgical residency programs in an effort to augment training. A wide range
      of simulator types and levels of complexity have proven an effective teaching
      method for surgical trainees. They have been used for training in areas such as
      general surgery, urology, gynecology, and ophthalmology among others. Coincident
      with the introduction of simulators is the need for objective evaluation of
      skills learned on them, which has led to the development and validation of
      multiple evaluation tools. This article evaluates the drivers for simulation,
      types of simulators, training, and evaluation of them especially as it pertains
      to laparoscopic colorectal surgery. 

PMID- 24436649
TI  - Integrating hospital administrative data to improve health care efficiency and
      outcomes: "the socrates story".
AB  - Evaluation of health care outcomes has become increasingly important as we strive
      to improve quality and efficiency while controlling cost. Many groups feel that
      analysis of large datasets will be useful in optimizing resource utilization;
      however, the ideal blend of clinical and administrative data points has not been
      developed. Hospitals and health care systems have several tools to measure cost
      and resource utilization, but the data are often housed in disparate systems that
      are not integrated and do not permit multisystem analysis. Systems Outcomes and
      Clinical Resources AdministraTive Efficiency Software (SOCRATES) is a novel data
      merging, warehousing, analysis, and reporting technology, which brings together
      disparate hospital administrative systems generating automated or customizable
      risk-adjusted reports. Used in combination with standardized enhanced care
      pathways, SOCRATES offers a mechanism to improve the quality and efficiency of
      care, with the ability to measure real-time changes in outcomes. 

PMID- 24436651
TI  - Crohn disease.

PMID- 24436652
TI  - Medical management of crohn disease.
AB  - Crohn disease (CD) is one of the major subtypes of inflammatory bowel disease and
      can occur in any segment of the alimentary tract. There have been significant
      advances in the medical therapy of CD over the past several decades. For mild CD,
      the oral corticosteroid derivative budesonide has demonstrated superior efficacy
      compared with traditional therapies such as 5-aminosalicylic acid, and can be
      used concurrently with these agents. For the management of moderate to severe
      disease, the immunomodulators azathioprine, 6-mercaptopurine, and methotrexate,
      as well as the antitumor necrosis factor-alpha (TNF-alpha) agents infliximab,
      adalimumab, and certolizumab pegol, have become the mainstay of therapy, with
      growing interest in combining these agents for maximal effect. Immunomodulators
      and anti-TNF-alpha agents have also demonstrated benefit in fistulizing CD. There
      has been growing evidence suggesting that both of these agents, along with the
      antibiotics metronidazole and ornidazole, are also effective in preventing
      postoperative recurrence of CD. 

PMID- 24436653
TI  - Preoperative optimization of crohn disease.
AB  - Crohn disease is a chronic disease that is treated with aminosalicylates,
      antibiotics, and immunosuppressant agents. Most patients ultimately require
      surgical intervention and many will require additional surgery for recurrent
      disease. Consequently, surgery is generally performed only when medical
      management fails; however, these patients are often malnourished and
      immunosuppressed. Preoperative optimization is necessary to minimize morbidity,
      including intra-abdominal septic complications and anastomotic leaks. In this
      article, the authors review some considerations to improve the surgical outcome
      in Crohn disease. 

PMID- 24436654
TI  - Strictureplasty.
AB  - Over the past three decades, strictureplasty for Crohn disease with fibrostenotic
      stricture has been shown to be both efficacious and safe. Although segmental
      resection remains the standard of care for obstruction secondary to Crohn
      stricture, strictureplasty should be considered for patients with a history of
      prior resections who are at increased risk for short bowel syndrome with
      additional resections. There is ample evidence to support both conventional and
      nonconventional strictureplasty techniques for both jejunoileal and ileocolonic
      anastomotic strictures. The role of strictureplasty for both duodenal and colonic
      disease, as well as the risk of malignant transformation at strictureplasty
      sites, is yet to be determined. 

PMID- 24436655
TI  - Colonic crohn disease.
AB  - Colonic Crohn disease is a complicated disease entity that requires a
      multidisciplinary effort on the part of the surgeon, gastroenterologist, and
      pathologist. Crohn disease affects ~500,000 people in North America with nearly
      300,000 people suffering from colonic manifestations. This represents a
      significant portion of the patient population in the typical colorectal surgeon's
      practice. As such, an intimate understanding of the disease process,
      presentation, and treatment options is imperative. In this article, the authors
      review the clinical manifestations, diagnosis, and medical and surgical treatment
      options with a focus on current strategies for surgical management. 

PMID- 24436657
TI  - Restorative procedures in colonic crohn disease.
AB  - Surgical management for refractory Crohn colitis often involves creation of a
      temporary or permanent stoma. Traditionally, the procedure of choice has been a
      total proctocolectomy with permanent ileostomy. However, restorative procedures
      that help to avoid a permanent stoma are being used with more frequency. In this
      article, the authors will address these procedures, including colocolonic
      anastomosis, ileorectal anastomosis, ileal pouch rectal anastomosis, and ileal
      pouch anal anastomosis. Factors that may influence one's decision to perform
      these procedures, such as patient age and nutritional status, medical
      comorbidities, sphincter function, desire to avoid a permanent ostomy, and prior
      medical therapy, will be discussed. Functional outcomes regarding these
      procedures will also be described. One should keep in mind that surgery does not
      cure Crohn disease and that postoperative long-term management is essential in
      preventing progression or recurrence of disease. 

PMID- 24436656
TI  - Surgical treatment of anorectal crohn disease.
AB  - Crohn disease involves the perineum and rectum in approximately one-third of
      patients. Symptoms can range from mild, including skin tags and hemorrhoids, to
      unremitting and severe, requiring a proctectomy in a small, but significant,
      portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation
      seen on presentation. Careful diagnosis, including magnetic resonance imaging or
      endorectal ultrasound with examination under anesthesia and aggressive medical
      management, usually with a tumor necrosis factor-alpha, is critical to success.
      Several options for definitive surgical repair are discussed, including
      fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and
      ligation of intersphincteric fistula tract procedure. All suffer from decreased
      efficacy in patients with Crohn disease. In the presence of active proctitis or
      perineal disease, no surgical therapy other than drainage of abscesses and loose
      seton placement is recommended, as iatrogenic injury and poor wound healing are
      common in that scenario. 

PMID- 24436658
TI  - Prevention and management of nonhealing perineal wounds.
AB  - Complex perineal wounds are at risk for nonhealing. High-risk procedures include
      proctectomy for Crohn disease, anal cancer and radiated distal rectal cancers. A
      basic understanding of both patient and procedural risk factors is helpful in
      planning and executing operative procedures for these conditions and to minimize
      associated wound complications. Diabetes, obesity, and malnutrition may
      contribute to wound breakdown and failure to heal. Delaying operative
      intervention, adding nutritional supplementation, and employing intestinal
      diversion as well as myocutaneous flaps may help optimize conditions for wound
      healing. 

PMID- 24436660
TI  - Laparoscopic surgery for crohn disease: a brief review of the literature.
AB  - Crohn disease remains a challenging clinical entity, both medically and
      surgically. It frequently presents in early adulthood and imposes a lifetime
      exposure to chronic inflammation that can affect the entire gastrointestinal
      tract. Although the mainstay of therapy is treatment with immunomodulating drugs,
      ~70 to 90% of patients with Crohn disease will ultimately require surgery.
      Furthermore, there are high rates of symptomatic recurrences that may also
      require surgical intervention over time. There is no definitive cure for Crohn
      disease and surgery is reserved for failed medical therapy or the complications
      of the disease, namely, obstruction, septic complications (abscess, perforation),
      and fistulas. However, the robust inflammatory environment during these periods
      is not always conducive to a minimally invasive surgical approach. Despite the
      inherent technical challenges, the literature has increasingly shown that
      laparoscopy for Crohn disease, in the appropriate setting, is feasible and safe.
      In fact, it offers many advantages, which are particularly beneficial to this
      subset of patients, such as fewer wound complications, a shortened hospital
      course, less tissue trauma and subsequent adhesion formation, and earlier
      resumption of oral intake and bowel function. 

PMID- 24436662
TI  - Sharon L. Stein, MD, FACS.

PMID- 24436659
TI  - Avoidance and management of stomal complications.
AB  - The construction of an intestinal stoma is fraught with complications and should
      not be considered a trivial undertaking. Serious complications requiring
      immediate reoperations can occur, as can minor problems that will subject the
      patient to daily and nightly distress. Intestinal stomas undoubtedly will
      dramatically change lifestyles; patients will experience physiologic and
      psychologic detriment with stoma-related problems, however minor they may seem.
      Common complications include poor stoma siting, high output, skin irritation,
      ischemia, retraction, parastomal hernia (PH), and prolapse. Surgeons should be
      cognizant of these complications before, during, and after stoma creation, and
      adequate measures should be taken to avoid them. In this review, the authors
      highlight these often seen problems and discuss management and prevention
      strategies. 

PMID- 24436661
TI  - Biologic therapy and surgery for crohn disease.
AB  - In 1998, infliximab, an antitumor necrosis factor alpha (anti-TNF-alpha)
      antibody, was approved for use in the treatment of Crohn disease (CD). Since
      then, other biologic therapies, including adalimumab and certolizumab pegol
      (newer anti-TNF-alpha antibodies), and natalizumab, an antibody against alpha-4
      integrin, have also been approved. Here, we review the published studies that
      examine the relationship between pre- and postoperative biologic therapy and
      postoperative complications in patients with CD. This body of literature is
      composed of numerous small, retrospective, heterogeneous studies that demonstrate
      conflicting and varied results. Overall, the receipt of biologic therapy in the
      pre- or postoperative period does not appear to significantly increase the risk
      of postoperative complications. It is, however, difficult to draw any firm
      conclusions based on the existing level of data. In the future, larger
      prospective studies are needed to better elucidate the true risks, if any, that
      the use of biologic therapy poses to patients with CD requiring operation. 

PMID- 24436663
TI  - Perioperative management.

PMID- 24436664
TI  - Perioperative protocols in colorectal surgery.
AB  - The reduction in health-care expenditures and more efficient use of medical
      resources are now overriding health policy priorities with the two-pronged goal
      of improving patient outcomes while decreasing overall cost. Current reports show
      colorectal surgery accounting for 25% of all operative complications and an
      average length of stay of 8 to 12 days for a standard elective colon resection.
      To combat this, Kehlet and colleagues introduced a concept of enhanced recovery
      after surgery (ERAS) or fast-track pathways, with the goal of using current
      evidence and multimodal therapies to decrease surgical stress, enhance
      postoperative recovery, and reduce length of stay. The benefits, safety, and cost
      effectiveness of fast-track protocols are validated in multiple randomized
      controlled trials. In this review, the authors focus on the evidence regarding
      fast-track pathways, use of minimally invasive surgery and its role in fast-track
      pathways, newer perioperative interventions, and future directions. 

PMID- 24436665
TI  - Bowel Preparation before Elective Surgery.
AB  - Mechanical bowel preps were initially thought to decrease the bacterial load of
      the colon and therefore decrease infection. Traditional bowel preps include
      osmotic, laxative, and combination regimen. Data demonstrate that mechanical
      bowel preps are generally equivalent; however, the addition of oral antibiotics
      may further reduce the risk of infection. Recent data suggest that mechanical
      bowel preparations may not be necessary, and that dietary restrictions before
      surgery may also be obsolete. In this review, the authors address the types of
      mechanical bowel preparations (MBPs), differences in outcomes between MBPs, the
      role of oral antibiosis and enemas, the benefits of no MBP, and dietary
      preparations for elective colon and rectal surgery. 

PMID- 24436667
TI  - Perioperative Beta blockade.
AB  - The use of preoperative beta (beta) blockade has been through several changes,
      and it is clear that large, randomized controlled trials on the subject are in
      need. Currently, a judicious approach to perioperative beta blockade is
      supported. Continuation of beta blockers is recommended for the patient taking
      them prior to surgery. Patients undergoing large colorectal procedures, with
      coronary artery disease or high cardiac risk, should have beta blockers titrated
      to heart rate and blood pressure. Dosages should be titrated to heart rate and
      blood pressure rather than using fixed, long-acting dosages. When beta blockers
      are indicated, they should be initiated weeks before surgery. 

PMID- 24436666
TI  - Venous thromboembolism prophylaxis.
AB  - Venous thromboembolism (VTE) can occur after major general surgery. Pulmonary
      embolism is recognized as the most common identifiable cause of death in
      hospitalized patients in the United States. The risk of deep venous thrombosis
      (DVT) and pulmonary embolism (PE) is higher in colorectal surgical procedures
      compared with general surgical procedures. The incidence of venous
      thromboembolism in this population is estimated to be 0.2 to 0.3%. Prevention of
      VTE is considered a patient-safety measure in most mandated quality initiatives.
      The measures for prevention of VTE include mechanical methods (graduated
      compression stockings and intermittent pneumatic compression devices) and
      pharmacologic agents. A combination of mechanical and pharmacologic methods
      produces the best results. Patients undergoing surgery should be stratified
      according to their risk of VTE based on patient risk factors, disease-related
      risk factors, and procedure-related risk factors. The type of prophylaxis should
      be commensurate with the risk of VTE based on the composite risk profile. 

PMID- 24436668
TI  - Perioperative stress-dose steroids.
AB  - Supraphysiologic corticosteroid doses have routinely been considered the
      perioperative standard of care over the past six decades for patients on long
      term steroid therapy. However, the accumulation of data over this period is
      beginning to suggest that such a practice may not be necessary. The majority of
      these studies are retrospective reviews or small prospective cohorts, but there
      are two small prospective, randomized placebo-controlled trials, one prospective
      primate trial, and several systematic reviews addressing the issue. Based on this
      developing evidence, patients on long-term exogenous steroids do not require high
      dose perioperative corticosteroids and should instead remain on their baseline
      maintenance dose, with the understanding that secondary adrenal insufficiency
      should be considered for unexplained perioperative hypotension in these patients.

PMID- 24436669
TI  - Perioperative strategies to prevent surgical-site infection.
AB  - Colon and rectal resections are among the most common surgical procedures
      performed in the United States. Complication rates of up to 25% have been
      reported and result in a substantial impact on quality of life and cost of care.
      Recently, the Surgical Care Improvement Program (SCIP) has promoted guidelines to
      prevent postoperative and potentially preventable complications. A comprehensive
      evidenced-based review of these guidelines and other perioperative strategies for
      practicing colorectal surgeons is the basis of this review. 

PMID- 24436670
TI  - Use of intra-abdominal drains.
AB  - The use of drains in colorectal surgery has been a subject of debate for several
      decades. Prophylactic drainage of the peritoneal cavity has become less popular
      in recent years. This change is due to several studies demonstrating that
      intraperitoneal drains do not adequately drain the peritoneal cavity and do not
      prevent or contain anastomotic leaks. Percutaneous drain placement has become the
      standard of care for patients with intra-abdominal abscesses. Selected
      anastomotic leaks in the stable patient can also be managed with percutaneous
      drains. In this article, the authors review in detail the use of drains and the
      literature to support their use in our everyday practice. 

PMID- 24436671
TI  - Urinary catheter management.
AB  - After colorectal resection surgery, early urinary catheter removal has been
      promoted as a part of the national Surgical Care Improvement Project. However,
      the decrease in urinary tract infection expected with this strategy must be
      balanced against an increased risk for urinary retention. A systematic review of
      the literature was undertaken to summarize the evidence for and against early
      postoperative urinary catheter removal. For nonpelvic colorectal resection, the
      evidence supports removal of the catheter on postoperative day 1 for patients who
      are not at high risk for urinary retention, including patients with thoracic
      epidurals. For mid-to-low rectal surgery, the risk of urinary retention is
      increased, and catheter removal on day 3 to day 6 is recommended; however, the
      exact timing of removal cannot be recommended based on current studies. 

PMID- 24436672
TI  - The Evidence against Prophylactic Nasogastric Intubation and Oral Restriction.
AB  - Evidence-based perioperative care plans after colorectal surgery serve to improve
      quality outcome, decrease complications, and reduce medical cost. The benefits of
      routine nasogastric decompression and prolonged enteral restriction after bowel
      resection are not supported in this new era of evidence-based surgical care.
      Prophylactic nasogastric decompression fails to improve bowel function, length of
      stay, and prevent anastomotic leak, wound complications (infection, fascial
      dehiscence, incisional hernia), pulmonary complications (atelectasis, aspiration,
      pneumonia, fever, pharyngolaryngitis), and abdominal discomfort (distension,
      nausea, vomiting). Patients have earlier return of bowel function without the use
      of a nasogastric tube (NGT). Early refeeding within 24 hours after bowel
      resection is well tolerated in 80 to 90% of patients, and associated with earlier
      hospital discharge, decreased risk of infection, and improved postoperative
      hyperglycemic control. Abdominal discomfort is the most common complication
      observed in patients treated with early feeding and without a NGT, but does not
      result in higher therapeutic nasogastric intubation, postoperative ileus,
      aspiration, or other complications. The use of multimodal adjuncts in combination
      with these guidelines should be considered to improve outcome. The current
      literature is reviewed with suggestions for achieving better outcomes after
      colorectal resection. 

PMID- 24436673
TI  - Facilitating return of bowel function after colorectal surgery: alvimopan and gum
      chewing.
AB  - Postoperative ileus is common after colorectal surgery, and has a huge impact on
      hospital LOS. With the impeding cost crisis in the United States, safely reducing
      length of stay is essential. Chewing gum and pharmacological treatment with
      alvimopan are safe, simple tools to reduce postoperative ileus and its associated
      costs. Future research will determine if integrating these tools with
      laparoscopic procedures and enhanced recovery pathways is a best practice in
      colorectal surgery. 

PMID- 24436674
TI  - Postoperative pain control.
AB  - The effective relief of pain is of the utmost importance to anyone treating
      patients undergoing surgery. Pain relief has significant physiological benefits;
      hence, monitoring of pain relief is increasingly becoming an important
      postoperative quality measure. The goal for postoperative pain management is to
      reduce or eliminate pain and discomfort with a minimum of side effects. Various
      agents (opioid vs. nonopioid), routes (oral, intravenous, neuraxial, regional)
      and modes (patient controlled vs. "as needed") for the treatment of postoperative
      pain exist. Although traditionally the mainstay of postoperative analgesia is
      opioid based, increasingly more evidence exists to support a multimodal approach
      with the intent to reduce opioid side effects (such as nausea and ileus) and
      improve pain scores. Enhanced recovery protocols to reduce length of stay in
      colorectal surgery are becoming more prevalent and include multimodal opioid
      sparing regimens as a critical component. Familiarity with the efficacy of
      available agents and routes of administration is important to tailor the
      postoperative regimen to the needs of the individual patient. 

PMID- 24436676
TI  - Karim Alavi, MD, MPH, FACS, FASCRS.

PMID- 24436675
TI  - Perioperative fluid restriction.
AB  - Perioperative fluid management of the colorectal surgical patient has evolved
      significantly over the last five decades. Older notions espousing aggressive
      hydration have been shown to be associated with increased complications. Newer
      data regarding fluid restriction has shown an association with improved outcomes.
      Management of perioperative fluid administration can be considered in three
      primary phases: In the preoperative phase, data suggests that avoidance of
      preoperative bowel preparation and avoidance of undue preoperative dehydration
      can improve outcomes. Although the type of intraoperative fluid given does not
      have a significant effect on outcome, data do suggest that a restrictive fluid
      regimen results in improved outcomes. Finally, in the postoperative phase of
      fluid management, a fluid-restrictive regimen, coupled with early enteral feeding
      also seems to result in improved outcomes. 

PMID- 24436677
TI  - Faculty development in surgery.

PMID- 24436678
TI  - Scholarship in academic surgery: history, challenges, and ideas for the future.
AB  - The role of academic surgery is changing. Traditional roles of the triple threat
      researcher, clinician and teacher, were formulated by Osler and improved upon by
      Boyle in the 1990s. These include application and integration of research to
      clinical problems. However, new pressures exist on the academic surgeon.
      Financial pressures rising costs of health care and decreased research funding
      all need to be addressed. In addition, retention and advancement of faculty is
      more difficult with increased emphasis of clinical practice in academic medicine.
      The future of academic medicine will require personal optimization as a
      multifaceted academician, businessman, and administrator, as well as rethinking
      how academic medicine may function in the future. 

PMID- 24436679
TI  - Academic goals in surgery.
AB  - The development of an academic surgical career can be an overwhelming prospect,
      and one that is not intuitive. Establishing a structured plan and support
      structure is critical to success. Starting a successful academic surgical career
      begins with defining one's academic goals within several broad categories:
      personal goals, academic goals, research goals, educational goals, and financial
      goals. Learning the art of self-promotion is the means by which many of these
      goals are achieved. It is important to realize that achieving these goals
      requires a delicate personal balance between work and home life, and the key ways
      in which to achieve success require establishment of well thought-out goals, a
      reliable support structure, realistic and clear expectations, and frequent re
      evaluation. 

PMID- 24436680
TI  - Mentorship.
AB  - The world of medicine is in a state of flux with major and substantive changes in
      its educational model. Students, residents, and junior attendings can no longer
      rely entirely on experiential development through clinical immersion. Instead, to
      attain similar levels of knowledge, technique, and situational comfort, there
      must be innovations in medical education that take advantage of the experience of
      mentors. Mentoring has been a part of medicine and surgery since the days of
      apprenticeship. Mentors must now teach more basic medicine than ever before and
      adapt to changes in the structure of medical education such as the use of
      simulation, yet still continue to foster career development among trainees and
      junior colleagues. For mentoring to succeed and benefit mentees, it must be
      supported. This patronage starts with each local university or hospital system
      but eventually must permeate the greater medical culture. 

PMID- 24436681
TI  - Funding sources in faculty development: strategies for success in submitting
      proposals.
AB  - Although the capacity for integrated research and potential for translating
      research findings to the clinical setting have never been stronger, we are
      paradoxically entering a period of highly constrained funding. It is more
      important than ever for clinician scientists and young researchers to be
      strategic in the approach to funding. The purpose of this article is to discuss
      strategies for a successful approach to appropriate grant funding agencies. 

PMID- 24436682
TI  - Grant writing 101.
AB  - Writing a grant is a hefty undertaking. Start by surrounding yourself with a
      successful mentor and accompanying team with a good track record. Get organized,
      select clear goals and objectives to your project. Once the foundation for the
      grant is set, begin by generating a robust hypothesis. Once your hypothesis is
      clearly defined, you should contact the project officer of the specific grant for
      which you are applying; they can help identify if the proposal meets an area of
      need. The basic components of a grant include the following: the face page, which
      highlights the key contributors; followed by table of contents; abstract;
      biographical sketches, which are minicurriculum vitae; budget; research plan,
      which is composed mostly of background, significance, and specific aims; and
      lastly, references cited. Be sure to follow specific formatting. Use resources
      including the internet to find an appropriate grant. Finally, given the confines
      of a busy surgical practice and the significant amount of work necessary to
      complete a grant, it is essential that the work begins early and well in advance
      of the proposed deadline. 

PMID- 24436683
TI  - Promotion.
AB  - This article gives an overview of the promotion process in an academic medical
      center. A description of different promotional tracks, tenure and endowed chairs,
      and the process of submitting an application is provided. Finally, some practical
      advice about developing skills and attributes that can help with academic growth
      and promotion is dispensed. 

PMID- 24436684
TI  - Effective time management: surgery, research, service, travel, fitness, and
      family.
AB  - Over 1,500 years ago, the St. Benedictine Monks used planning and strict
      schedules to increase their productivity. Since then, surgeons have developed
      several different strategies to manage our time effectively. Finding a balance
      among career, family, and hobbies is essential for maintaining satisfaction and
      optimizing productivity. Several recurring themes throughout the medical
      literature offer potential solutions to help maximize the little time surgeons
      possess. In this article, we will explore some of the methods and strategies
      available to help surgeons minimize waste and make the most of the most precious
      commodity we have-our time. 

PMID- 24436685
TI  - Effective teaching and feedback strategies in the or and beyond.
AB  - Maintaining a standard of excellence for graduating surgical residents requires a
      comprehensive and consistent approach to surgical education. The omnipresent and
      increasing barriers to education must also be recognized and addressed. The
      implementation of effective teaching strategies is largely dependent on the
      resources available at each institution and the vision of education.
      Unfortunately, allocating time for surgeons to teach both inside and outside the
      operating room has become a foreign concept to administration. Furthermore, the
      reduction in case numbers performed by trainees now demands "quality over
      quantity" to ensure success. Quality teaching moments will only be realized when
      emphasis is placed on preparation, useful instruction during the procedure, and
      postoperative feedback. Ideal preparation entails a detailed discussion between
      the trainee and surgeon about the specific learning goals for the case. During
      the procedure, the faculty surgeon must strive to maximize the experience through
      effective communication while performing an efficient and safe operation.
      Numerous validated objective assessment tools exist for postprocedure evaluation
      but are grossly underutilized. Surgical education must thoughtfully be approached
      with the same fervor and detail as patient care. As faculty, it is our
      responsibility to train the next generation of surgeons and therefore "every case
      must count." 

PMID- 24436686
TI  - Advanced degrees in academic colorectal surgery.
AB  - Because of the increasing complexity of medical care, growing numbers of
      physicians are supplementing their medical education with additional training in
      basic research, public health, and leadership/business. The doctor of philosophy,
      master of public health, and master of business administration are popular
      degrees that give matriculants added levels of knowledge and expertise in their
      respective fields. This article reviews the relative advantages and disadvantages
      of each degree as they relate to a career in surgery. Data regarding the academic
      and financial outcomes of students obtaining these degrees are reviewed. 

PMID- 24436687
TI  - Leadership in surgery.
AB  - Many opportunities exist for surgeons to be leaders in healthcare. Leadership
      training should begin in medical school and continue throughout residency
      training and in clinical practice. Most leadership skills can be developed and
      refined through a variety of training programs. Formal programs that result in
      degrees can provide surgeons with special insight, experience, and skill sets.
      Leadership skills are used in everyday practice and are particularly valuable
      when shifting roles or taking on new positions, whether at your home institution
      or within national organizations. Ultimately, physician leaders are responsible
      for leading healthcare and will directly impact the quality of care delivered to
      our patients. 

PMID- 24436688
TI  - Conflict management: difficult conversations with difficult people.
AB  - Conflict occurs frequently in any workplace; health care is not an exception. The
      negative consequences include dysfunctional team work, decreased patient
      satisfaction, and increased employee turnover. Research demonstrates that
      training in conflict resolution skills can result in improved teamwork,
      productivity, and patient and employee satisfaction. Strategies to address a
      disruptive physician, a particularly difficult conflict situation in healthcare,
      are addressed. 

PMID- 24436689
TI  - Long Timestep Molecular Dynamics on the Graphical Processing Unit.
AB  - Molecular dynamics (MD) simulations now play a key role in many areas of
      theoretical chemistry, biology, physics, and materials science. In many cases,
      such calculations are significantly limited by the massive amount of computer
      time needed to perform calculations of interest. Herein, we present Long Timestep
      Molecular Dynamics (LTMD), a method to significantly speed MD simulations. In
      particular, we discuss new methods to calculate the needed terms in LTMD as well
      as issues germane to a GPU implementation. The resulting code, implemented in the
      OpenMM MD library, can achieve a significant 6-fold speed increase, leading to MD
      simulations on the order of 5 MUs/day using implicit solvent models.

PMID- 24436690
TI  - Religiosity and Function Among Community-Dwelling Older Adult Survivors of
      Cancer.
AB  - Aspects of religiosity/spirituality are important to health and quality of life
      of cancer patients. The three components of religiosity of the Duke Religiosity
      Scale: organizational (religious affiliation and attendance); non-organizational
      (prayer, meditation, and private study); and intrinsic religiosity
      (identification with a higher power and integration of spiritual belief into
      daily life) are used to determine whether religiosity was associated with
      physical and/or mental functioning among older cancer survivors of the UAB Study
      of Aging. Church attendance was independently associated with lower ADL and IADL
      difficulty and fewer depressive symptoms, while intrinsic religiosity was
      independently associated with lower depression scores.

PMID- 24436691
TI  - Software-programmable continuous-flow multi-purpose lab-on-a-chip.
AB  - Current lab-on-a-chip (LoC) devices are assay-specific and are custom-built for
      each single experiment. Performing an experiment requires scientists or engineers
      to go through the time-consuming process of designing, fabricating, and testing a
      chip before conducting the actual experiment. This prolonged cycle can take
      months to complete, increasing effort and cost and reducing productivity.
      Similarly, minor modifications to an assay protocol re-incur the overheads of the
      design cycle. In this paper, we develop a multi-purpose, software-programmableLab
      on-a-Chip (SPLoC), where the user simply writes or downloads a program for each
      experiment. We describe the components necessary to realize the SPLoC, which
      include a high-level programming language, an abstract instruction set, a runtime
      and control system, and a microfluidic device. We describe two key features of
      our high-level language compiler, and describe a novel variable-volume variable
      ratio mixer. Finally, we demonstrate our SPLoC on four diverse, real-world
      assays.

PMID- 24436692
TI  - Measuring success in spine care.

PMID- 24436693
TI  - Economic studies part 2: evaluating the quality.

PMID- 24436694
TI  - Altered spinal motion in low back pain associated with lumbar strain and
      spondylosis.
AB  - Study Design We present a patient-specific computer model created to translate
      two-dimensional (2D) fluoroscopic motion data into three-dimensional (3D) in vivo
      biomechanical motion data. Objective The aim of this study is to determine the in
      vivo biomechanical differences in patients with and without acute low back pain.
      Current dynamic imaging of the lumbar spine consists of flexion-extension static
      radiographs, which lack sensitivity to out-of-plane motion and provide incomplete
      information on the overall spinal motion. Using a novel technique, in-plane and
      coupled out-of-plane rotational motions are quantified in the lumbar spine.
      Methods A total of 30 participants-10 healthy asymptomatic subjects, 10 patients
      with low back pain without spondylosis radiologically, and 10 patients with low
      back pain with radiological spondylosis-underwent dynamic fluoroscopy with a 3D
      to-2D image registration technique to create a 3D, patient-specific bone model to
      analyze in vivo kinematics using the maximal absolute rotational magnitude and
      the path of rotation. Results Average overall in-plane rotations (L1-L5) in
      patients with low back pain were less than those asymptomatic, with the dominant
      loss of motion during extension. Those with low back pain also had significantly
      greater out-of-plane rotations, with 5.5 degrees (without spondylosis) and 7.1
      degrees (with spondylosis) more out-of-plane rotational motion per level compared
      with asymptomatic subjects. Conclusions Subjects with low back pain exhibited
      greater out-of-plane intersegmental motion in their lumbar spine than healthy
      asymptomatic subjects. Conventional flexion-extension radiographs are inadequate
      for evaluating motion patterns of lumbar strain, and assessment of 3D in vivo
      spinal motion may elucidate the association of abnormal vertebral motions and
      clinically significant low back pain. 

PMID- 24436695
TI  - Early Morbidity of Multilevel Anterior Cervical Discectomy and Fusion with
      Plating for Spondylosis: Does the Number of Levels Influence Early Complications?
      A Single Surgeon's Experience in 519 Consecutive Patients.
AB  - Study Design This is a retrospective review of a prospectively maintained
      database of anterior cervical discectomy and fusion with plating (ACDFP) cases.
      Objective The aim of this study is to evaluate within a clinical practice
      evidence-based results of short-term morbidity with multilevel ACDFP. Methods
      Clinical morbidity, length of hospital stay, visual analog scale (VAS) and Odom
      scores, Neck Disability Index (NDI), hardware failure, and return-to-work (RTW)
      status were prospectively collected in an electronic database for 678 patients
      who underwent 1-, 2-, 3-, or 4-level ACDFP during an 8-year period. A total of
      519 patients met the study criteria and were retrospectively analyzed. Results
      The majority of all patients noted "Excellent" or "Good" status for 1 month
      (91%), 2 months (92%), and 3 months (96%). Patients with 1-, 2-, and 3-level
      ACDFP returned to work sooner, 60% at 1 month, 70% at 2 months, and 68% at 3
      months. For 4-level patients, the majority did not RTW until 3 months (71%). The
      only significant increase in morbidity with increasing levels was hospital stay
      for 3- and 4-level ACDFP and RTW for 4-level ACDFP. Conclusion Multilevel ACDFP
      can be performed with low initial morbidity. An individual practice can review
      results to allow for ongoing evidence-based care. [Table: see text]. 

PMID- 24436696
TI  - Vertebral Osteotomies in Ankylosing Spondylitis-Comparison of Outcomes Following
      Closing Wedge Osteotomy versus Opening Wedge Osteotomy: A Systematic Review.
AB  - Study Design Systematic review. Study Rationale To seek out and assess the best
      quality evidence available comparing opening wedge osteotomy (OWO) and closing
      wedge osteotomy (CWO) in patients with ankylosing spondylitis to determine
      whether their results differ with regard to several different subjective and
      objective outcome measures. Objective The aim of this study is to determine
      whether there is a difference in subjective and objective outcomes when comparing
      CWO and OWO in patients with ankylosing spondylitis suffering from clinically
      significant thoracolumbar kyphosis with respect to quality-of-life assessments,
      complication risks, and the amount of correction of the spine achieved at follow
      up. Methods A systematic review was undertaken of articles published up to July
      2012. Electronic databases and reference lists of key articles were searched to
      identify studies comparing effectiveness and safety outcomes between adult
      patients with ankylosing spondylitis who received closing wedge versus opening
      wedge osteotomies. Studies that included pediatric patients, polysegmental
      osteotomies, or revision procedures were excluded. Two independent reviewers
      assessed the strength of evidence using the GRADE criteria and disagreements were
      resolved by consensus. Results From a total of 67 possible citations, 4
      retrospective cohorts (class of evidence III) met our inclusion criteria and form
      the basis for this report. No differences in Oswestry Disability Index, visual
      analog scale for pain, Scoliosis Research Society (SRS)-24 score, SRS-22 score,
      and patient satisfaction were reported between the closing and opening wedge
      groups across two studies. Regarding radiological outcomes following closing
      versus opening osteotomies, mean change in sagittal vertical axis ranged from 8.9
      to 10.8 cm and 8.0 to 10.9 cm, respectively, across three studies; mean change in
      lumbar lordosis ranged from 36 to 47 degrees and 19 to 41 degrees across four
      studies; and mean change in global kyphosis ranged from 38 to 40 degrees and 28
      to 35 degrees across two studies. Across all studies, overall complication risks
      ranged from 0 to 16.7% following CWO and from 0 to 23.6% following OWO.
      Conclusion No statistically significant differences were seen in patient-reported
      or radiographic outcomes between CWO and OWO in any study. The risks of dural
      tear, neurological injury, and reoperation were similar between groups. Blood
      loss was greater in the closing wedge compared with the opening wedge group,
      while the risk of paralytic ileus was less. The overall strength of evidence for
      the conclusions is low. 

PMID- 24436697
TI  - The outcomes of manipulation or mobilization therapy compared with physical
      therapy or exercise for neck pain: a systematic review.
AB  - Study Design Systematic review. Study Rationale Neck pain is a prevalent
      condition. Spinal manipulation and mobilization procedures are becoming an
      accepted treatment for neck pain. However, data on the effectiveness of these
      treatments have not been summarized. Objective To compare manipulation or
      mobilization of the cervical spine to physical therapy or exercise for symptom
      improvement in patients with neck pain. Methods A systematic review of the
      literature was performed using PubMed, the National Guideline Clearinghouse
      Database, and bibliographies of key articles, which compared spinal manipulation
      or mobilization therapy with physical therapy or exercise in patients with neck
      pain. Articles were included based on predetermined criteria and were appraised
      using a predefined quality rating scheme. Results From 197 citations, 7 articles
      met all inclusion and exclusion criteria. There were no differences in pain
      improvement when comparing spinal manipulation to exercise, and there were
      inconsistent reports of pain improvement in subjects who underwent mobilization
      therapy versus physical therapy. No disability improvement was reported between
      treatment groups in studies of acute or chronic neck pain patients. No functional
      improvement was found with manipulation therapy compared with exercise treatment
      or mobilization therapy compared with physical therapy groups in patients with
      acute pain. In chronic neck pain subjects who underwent spinal manipulation
      therapy compared to exercise treatment, results for short-term functional
      improvement were inconsistent. Conclusion The data available suggest that there
      are minimal short- and long-term treatment differences in pain, disability,
      patient-rated treatment improvement, treatment satisfaction, health status, or
      functional improvement when comparing manipulation or mobilization therapy to
      physical therapy or exercise in patients with neck pain. This systematic review
      is limited by the variability of treatment interventions and lack of standardized
      outcomes to assess treatment benefit. 

PMID- 24436698
TI  - Neck Pain Following Cervical Laminoplasty: Does Preservation of the C2 Muscle
      Attachments and/or C7 Matter?
AB  - Study Design Systematic review. Objective In patients aged 18 years or older,
      with cervical spondylotic myelopathy or ossification of the posterior
      longitudinal ligament (OPLL), does sparing the C2 muscle attachments and/or C7
      preserving cervical laminoplasty lead to reduced postoperative axial pain
      compared with conventional C3 to C7 laminoplasty? Do these results vary based on
      early active postoperative cervical motion? Methods A systematic review of the
      English-language literature was undertaken for articles published between 1970
      and August 17, 2012. Electronic databases and reference lists of key articles
      were searched to identify studies evaluating C2/C3- or C7-preserving cervical
      laminoplasty for the treatment of cervical spondylotic myelopathy (CSM) or OPLL
      in adults. Studies involving traumatic onset, cervical fracture, infection,
      deformity, or neoplasms were excluded, as were noncomparative studies. Two
      independent reviewers assessed the level of evidence quality using the grading of
      recommendations assessment, development and evaluation (GRADE) system, and
      disagreements were resolved by consensus. Results We identified 11 articles
      meeting our inclusion criteria. Only the randomized controlled trial (RCT) showed
      no significant difference in late axial pain (at 12 months) when C7 spinous
      muscle preservation was compared with no preservation. However, seven other
      retrospective cohort studies showed significant pain relief in the preserved
      group compared with the nonpreserved group. The preservation group included those
      with preservation of the C7 spinous process and/or attached muscles, the deep
      extensor muscles, or C2 muscle attachment and/or C3 laminectomy (as opposed to
      laminoplasty). One study that included preservation of either the C2 or C7
      posterior paraspinal muscles found that only preservation of the muscles attached
      to C2 resulted in reduced postoperative pain. Another study that included
      preservation of either the C7 spinous process or the deep extensor muscles found
      that only preservation of C7 resulted in reduced postoperative pain. Conclusion
      Although there is conflicting data regarding the importance of preserving C7
      and/or the semispinalis cervicis muscle attachments to C2, there is enough
      evidence to suggest that surgeons should make every attempt to preserve these
      structures whenever possible since there appears to be little downside to doing
      so, unless it compromises the neurologic decompression. 

PMID- 24436699
TI  - Thoracic spinal metastasis of merkel cell carcinoma in an immunocompromised
      patient: case report.
AB  - Study Design Case report. Objective Merkel cell carcinoma (MCC), an uncommon
      cutaneous neuroendocrine malignancy, is a rare cause of spinal metastasis, with
      only five cases previously reported. We report a rare case of MCC metastatic to
      the spine in an immunocompromised patient. Methods A 55-year-old male with
      previously resected MCC, immunocompromised due to cardiac transplant, presented
      with sharp mid-thoracic back pain radiating around the trunk to the midline.
      Computed tomography of the thoracic spine showed a dorsal epidural mass from T6
      to T8 with compression of the spinal cord. Laminectomy and subtotal tumor
      resection were performed, and pathology confirmed Merkel cell tumor through
      immunohistochemistry staining positive for cytokeratin 20 and negative for
      thyroid transcription factor-1. Results Further treatment with radiation therapy
      was initiated, and the patient did well for 4 months after surgery, but returned
      with a lesion in the cervical spine. He then opted for hospice care. Conclusions
      With an increasing number of immunocompromised patients presenting with back
      pain, MCC should be considered in the differential diagnosis of spinal metastatic
      disease. 

PMID- 24436700
TI  - Vascularized fibula strut graft used in neurofibromatosis type 1-related
      kyphosis: a case of almost complete reversal of deformity-induced tetraparesis.
AB  - Study Design Case report. Objective The aim of this study is to describe a case
      of vascularized fibula strut graft implanted in the cervicothoracic spine of a
      patient with neurofibromatosis type 1-related progressive kyphosis. Methods A
      detailed history examination of the surgical procedures and the results of the
      follow-up after fibula strut graft implantation were performed. In addition, a
      review of the literature was conducted to access the incidence of similar cases
      with an almost complete reversal of a deformity-induced tetraparesis. Results A
      37-year-old man with severe type 1 neurofibromatosis causing a collapsing
      kyphosis of the cervicothoracic spine presented in 2006 with progressive low
      cervical tetraparesis. Intervention included posterior stabilization (C5 to T5)
      which was extended to C3-T9 in 2008; however, the kyphosis continued to worsen.
      In 2009, a vascularized fibula strut graft was implanted between the inferior and
      superior endplates of C3 and T9. Over the following months, the patient gradually
      recovered motor strength and improved functional use of all limbs. In March 2011,
      lower limb (bilateral) and right arm strength was grade 5, with left arm strength
      being grade 4+. Conclusions This case report demonstrates the existence of a
      potential local option for the difficult problems of pseudoarthrosis, progressive
      spinal deformity, and cord compromise in patients with neurofibromatosis type 1
      related kyphosis resulting in an almost complete reversal of deformity-induced
      tetraparesis. 

PMID- 24436701
TI  - Surgical management of giant multilevel aneurysmal bone cyst of cervical spine in
      a 10-year-old child: case report with review of literature (evid based spine care
      j 2012;3(4):55-59).

PMID- 24436702
TI  - Spine Wars: The Lessons of YODA.

PMID- 24436703
TI  - Asking the right question: specifying your study question.

PMID- 24436704
TI  - A validated classification for external immobilization of the cervical spine.
AB  - Study Design Interobserver and intraobserver reliability study. Objective The aim
      of this study is to validate a new classification system of external cervical
      spine immobilization devices by measuring the interobserver and intraobserver
      agreement. Methods A classification system, with five main categories, based on
      the anatomical regions on which the device supports, was created. A total of 28
      independent observers classified 50 photographs of different devices, designed to
      immobilize the cervical spine according to the new proposed classification
      system. At least 2 weeks later, the same devices were classified again in a new
      random order. Before and after the classification, all the participants answered
      questions about the usefulness of the proposed classification. Results The mean
      interobserver and intraobserver agreement Fleiss' kappa was 0.88 and 0.91,
      respectively. Both are, according to the interpretation described by Landis and
      Koch, "almost perfect." A majority of the participators answered that they needed
      a classification (89%) and considered the classification to be clear (96%). All
      the participants considered the classification to be useful in clinical practice.
      Conclusion This study showed that the new classification of external cervical
      spine immobilizers, based on anatomical support areas, has an excellent
      interobserver and intraobserver agreement. Furthermore, the study participants
      considered the proposed classification to be clear and useful in clinical
      practice. As the majority of patients with cervical spine injuries are treated
      with external immobilization devices, this new classification system can improve
      the closed treatment of cervical spine injuries in daily clinical practice.
      Furthermore, it makes reproducible comparisons between groups possible, which are
      essential for further evolution of evidence-based spine care. 

PMID- 24436705
TI  - A comparison of radiostereometric analysis and computed tomography for the
      assessment of lumbar spinal fusion in a sheep model.
AB  - Study Design Prospective animal study. Objective The aim of this animal study is
      to evaluate the accuracy of radiostereometric analysis (RSA) compared with
      computed tomographic (CT) scan in the assessment of spinal fusion after anterior
      lumbar interbody fusion (ALIF) using histology as a gold standard. Methods Three
      non-adjacent ALIFs (L1-L2, L3-L4, and L5-L6) were performed in nine sheep. The
      sheep were divided into three groups of three sheep. All the animals were
      humanely killed immediately after having the last scheduled RSA. The lumbar spine
      was removed and in vitro fine cut CT and histopathology were performed. Results
      Using histological assessment as the gold standard for assessing fusion, RSA
      demonstrated better results (100% sensitivity and 66.7% specificity; positive
      predictive value [PPV] = 27.3%, negative predictive value [NPV] =100.0%) compared
      with CT (66.7% sensitivity and 60.0% specificity [PPV = 16.7%, NPV = 93.8%]).
      Conclusions RSA demonstrated higher sensitivity and specificity when compared
      with CT. Furthermore, RSA has the advantage of much lower radiation exposure
      compared with fine cut CT. Further studies are required to see if RSA remains
      superior to CT scan for the assessment spinal fusion in the clinical setting.
      [Table: see text]. 

PMID- 24436706
TI  - Success in academic spine surgery: the role of mentoring.

PMID- 24436707
TI  - Outcomes in adult scoliosis patients who undergo spinal fusion stopping at L5
      compared with extension to the sacrum.
AB  - Study Design Systematic review. Study Rationale Adult scoliosis is a common
      disorder that is associated with significantly higher pain, functional
      impairment, and effect on quality of life than those without scoliosis. Surgical
      spinal fusion has led to quantifiable improvement in patient's quality of life.
      However, for patients undergoing long lumbar fusion, the decision to stop the
      fusion at L5 or to extend to S1, particularly if the L5-S1 disc is healthy,
      remains controversial. Objective The aim of the study is to evaluate if fusion
      stopping at L5 increases the comparative rates of revision, correction loss,
      and/or poor functional outcomes compared with extension to the sacrum in adult
      scoliosis patients who require spinal fusion surgery. Materials and Methods A
      systematic review of the literature was performed using PubMed, the National
      Guideline Clearinghouse Database and bibliographies of key articles that
      evaluated adult scoliosis patients who required spinal fusion surgery and
      compared outcomes for fusions to the sacrum versus stopping at L5. Articles were
      included on the basis of predetermined criteria and were appraised using a
      predefined quality-rating scheme. Results From 111 citations, 26 articles
      underwent full-text review, and 3 retrospective cohort studies met all inclusion
      and exclusion criteria. Revision rates in subjects who underwent spinal fusion to
      L5 (20.8-23.5%) were lower in two studies compared with those with fusion
      extending to the sacrum (19.0-58.3%). Studies that assessed deformity correction
      used different measures, making comparison across studies difficult. No
      significant differences were found in patient-reported functional outcomes across
      two studies that used different measures. Conclusion The limited data available
      suggest that differences in revision rates did not consistently reach statistical
      significance across studies that compared spinal fusion to L5 versus extension to
      sacrum in adult scoliosis patients. 

PMID- 24436708
TI  - Comparative effectiveness of different types of cervical laminoplasty.
AB  - Study Design Systematic review. Study Rationale Numerous cervical laminoplasty
      techniques have been described but there are few studies that have compared these
      to determine the superiority of one over another. Clinical Questions The clinical
      questions include key question (KQ)1: In adults with cervical myelopathy from
      ossification of the posterior longitudinal ligament (OPLL) or spondylosis, what
      is the comparative effectiveness of open door cervical laminoplasty versus French
      door cervical laminoplasty? KQ2: In adults with cervical myelopathy from OPLL or
      spondylosis, are postoperative complications, including pain and infection,
      different for the use of miniplates versus the use of no plates following
      laminoplasty? KQ3: Do these results vary based on early active postoperative
      cervical motion? Materials and Methods A systematic review of the English
      language literature was undertaken for articles published between 1970 and March
      11, 2013. Electronic databases and reference lists of key articles were searched
      to identify studies evaluating (1) open door cervical laminoplasty and French
      door cervical laminoplasty and (2) the use of miniplates or no plates in cervical
      laminoplasty for the treatment of cervical spondylotic myelopathy or OPLL in
      adults. Studies involving traumatic onset, cervical fracture, infection,
      deformity, or neoplasms were excluded, as were noncomparative studies. Two
      independent reviewers (A.L.R., J.R.D.) assessed the level of evidence quality
      using the Grades of Recommendations Assessment, Development and Evaluation
      system, and disagreements were resolved by consensus. Results We identified three
      studies (one of class of evidence [CoE] II and two of CoE III) meeting our
      inclusion criteria comparing open door cervical laminoplasty with French door
      laminoplasty and two studies (one CoE II and one CoE III) comparing the use of
      miniplates with no plates. Data from one randomized controlled trial (RCT) and
      two retrospective cohort studies suggest no difference between treatment groups
      regarding improvement in myelopathy. One RCT reported significant improvement in
      axial pain and significantly higher short-form 36 scores in the French door
      laminoplasty treatment group. Overall, complications appear to be higher in the
      open door group than the French door group, although complete reporting of
      complications was poor in all studies. Overall, data from one RCT and one
      retrospective cohort study suggest that the incidence of complications (including
      reoperation, radiculopathy, and infection) is higher in the no plate treatment
      group compared with the miniplate group. One RCT reported greater pain as
      measured by the visual analog scale score in the no plate treatment group. There
      was no evidence available to assess the effect of early cervical motion for open
      door cervical laminoplasty compared with French door laminoplasty. Both studies
      comparing the use of miniplates and no plates reported early postoperative
      motion. Evidence from one RCT suggests that earlier postoperative cervical motion
      might reduce pain. Conclusion Data from three comparative studies are not
      sufficient to support the superiority of open door cervical laminoplasty or
      French door cervical laminoplasty. Data from two comparative studies are not
      sufficient to support the superiority of the use of miniplates or no plates
      following cervical laminoplasty. The overall strength of evidence to support any
      conclusions is low or insufficient. Thus, the debate continues while opportunity
      exists for the spine surgery community to resolve these issues with appropriately
      designed clinical studies. 

PMID- 24436709
TI  - Persistent/Recurrent syringomyelia after Chiari decompression-natural history and
      management strategies: a systematic review.
AB  - Study Design Systematic review. Study Rationale One of the most consistent
      indications for a Chiari decompression is tonsillar descent meeting the
      radiographic criteria and an associated syrinx in a symptomatic patient. In
      counseling patients about surgery, it would be advantageous to have information
      regarding the expected outcome with regard to the syrinx and other possible
      treatments available if the result is suboptimal. Clinical Questions The clinical
      questions include: (1) What is the average rate of recurrent or residual
      syringomyelia following posterior fossa decompression as a result of Chiari
      malformation with associated syringomyelia? (2) What treatment methods have been
      reported in the literature for managing recurrent or residual syringomyelia after
      initial posterior fossa decompression? Materials and Methods Available search
      engines were utilized to identify publications dealing with recurrent or residual
      syrinx after Chiari decompression and/or management of the syrinx. Rates of
      residual or recurrent syrinx were extracted and management strategies were
      recorded. Overall strength of evidence was quantified. Results Of the 72
      citations, 11 citations met inclusion criteria. Rates of recurrent/residual
      syringomyelia after decompression in adults range from 0 to 22% with an average
      of 6.7%. There were no studies that discussed specifically management of the
      remaining syrinx. Conclusion Rates of recurrent/residual syringomyelia after
      Chiari decompression in adults range from 0 to 22% (average 6.7%). Although no
      studies describing the optimal management of residual syrinx were found, there is
      general agreement that the aim of the initial surgery is to restore relatively
      unimpeded flow of cerebrospinal across the craniocervical junction. Large
      holocord syrinx may induce a component of spinal cord injury even with adequate
      decompression and reduction in the caliber of the syrinx, resulting in permanent
      symptoms of injury. 

PMID- 24436710
TI  - An extension-distraction injury of the thoracic spine with traumatic partial
      correction of thoracic kyphosis.
AB  - Study Design The study is a case report. Objective The authors aim to report an
      unusual injury pattern in a patient previously treated for thoracic
      kyphoscoliosis. Methods A postoperative (computed tomography) CT of a healthy 24
      year-old man who underwent posterior instrumentation and fusion for a
      kyphoscoliosis deformity was compared with a CT performed after a motor vehicle
      accident (MVA) 1 year later, which resulted in an extension-distraction injury of
      T8 with no neurologic deficit. Cobb angles of the thoracic sagittal images of
      both CTs were measured using a digital measuring device and the values were
      recorded. Results Initial postoperative sagittal CT images demonstrate a 67
      degree residual thoracic kyphosis compared with the post-MVA sagittal CT images,
      which reveal a 54-degree thoracic kyphosis, a 13-degree improvement in sagittal
      alignment. Conclusion It is unusual for a patient with long posterior
      instrumentation of the spine to sustain a spinal fracture without breakage of the
      rods, which were 6-mm nickel-titanium alloy with two crosslinks. Although
      sustaining plastic deformation, the rods maintained their integrity to the degree
      that the patient required no subsequent treatment to his spine at 12 months
      follow-up. It is rare to sustain a vertebral fracture without implant failure,
      which occurred in this case. 

PMID- 24436711
TI  - Occam paradox? A variation of tapia syndrome and an unreported complication of
      guidewire-assisted pedicle screw insertion.
AB  - Study Design Case report. Clinical Question The clinical aim is to report on a
      previously unknown association between guidewire-assisted pedicle screw insertion
      and neuropraxia of the recurrent laryngeal nerve (RLN), and how this may overlap
      with the signs of Tapia syndrome; we also report our approach to the clinical
      management of this patient. Methods A 17-year-old male patient with idiopathic
      scoliosis experienced Tapia syndrome after posterior instrumentation and
      arthrodesis at the level of T1-L1. After extubation, the patient had a hoarse
      voice and difficulty in swallowing. Imaging showed a breach in the cortex of the
      anterior body of T1 corresponding to the RLN on the right. Results
      Otolaryngological examination noted right vocal fold immobility, decreased
      sensation of the endolarynx, and pooling of secretions on flexible laryngoscopy
      that indicated right-sided cranial nerve X injury and left-sided tongue
      deviation. Aspiration during a modified barium swallow prompted insertion of a
      percutaneous endoscopic gastrostomy tube before the patient was sent home. On
      postoperative day 20, a barium swallow demonstrated reduced aspiration, and the
      patient reported complete resolution of symptoms. The feeding tube was removed,
      and the patient resumed a normal diet 1 month later. Tapia syndrome, or
      persistent unilateral laryngeal and hypoglossal paralysis, is an uncommon
      neuropraxia, which has previously not been observed in association with a
      breached vertebral body at T1 along the course of the RLN. Conclusion Tapia
      syndrome should be a differential diagnostic consideration whenever these
      symptoms persist postoperatively and spine surgeons should be aware of this as a
      potential complication of guidewires in spinal instrumentation. 

PMID- 24436712
TI  - Desmoid Tumor Formation following Posterior Spinal Instrumentation Placement.
AB  - Study Design Case report. Objective The objective of the article is to illustrate
      a case of desmoid tumor (DT) formation after posterior instrumentation of the
      thoracic spine. Methods A 57-year-old woman presented with lower extremity
      clumsiness, balance, and ambulation difficulty resulting from spinal cord
      compression due to an upper thoracic atypical vertebral hemangioma. Ten months
      after undergoing embolization, resection, and placement of instrumentation for
      this lesion, the patient developed a growing mass at the rostral end of the
      incision. Biopsy revealed desmoid fibromatosis. The mass was removed via an en
      bloc resection. Histology revealed an infiltrative DT above the laminectomy site
      abutting the instrumentation. Results At 2-year follow-up, there was no evidence
      of recurrence of the tumor. Conclusion Paraspinal DTs have been reported in the
      literature to develop after surgical procedures of the spine. Often times,
      patients attribute swelling or fullness at the site of their surgery to scar
      tissue formation or instrumentation. One must consider the possibility of a DT in
      the setting of reported surgical site fullness or mass after spine surgery. It is
      thought that postoperative inflammation present in the surgical bed may promote
      formation of DTs. Instrumentation may also contribute to inflammation and
      increase the likelihood of developing a DT. Generous margins must be taken to
      prevent recurrence. 

PMID- 24436713
TI  - Alternative Surgical Strategy for AxiaLIF Pseudarthrosis: A Series of Three Case
      Reports.
AB  - Study Design Retrospective case series. Objective The objective of this study is
      to describe an alternative technique to attain interbody lumbar fusion in the
      event of pseudarthrosis after axial lumbar interbody fusion (AxiaLIF) and to
      assess its safety. Methods Three patients who suffered from pseudarthrosis after
      AxiaLIF underwent revision surgery with a DEVEX cage (DePuy Synthes, Raynham, MA,
      United States) through an anterior approach. We report technical details as well
      as clinical and radiological results at 12 months follow-up. Results Preoperative
      symptoms resolved in all cases. There were no perioperative complications. One
      patient had a deep venous thrombosis at postoperative day 9. A decrease in visual
      analog scale score for pain was observed, from 8.67 preoperatively to 2
      postoperatively at final follow-up. Radiographic workup after 12 months showed no
      sign of implant failure or loosening, and fusion was obtained in all cases.
      Conclusion Anterior fusion with a DEVEX cage in front of a TranS1 screw (TranS1
      screw, Inc., Wilmington, North Carolina, United States) for AxiaLIF
      pseudarthrosis is safe and effective. 

PMID- 24436714
TI  - Periaortic pedicle screw removal with endovascular control of the aorta and
      intraoperative aortography: a case report and review of the literature.
AB  - Study Design  Case report and review of the literature. Objective The objective
      of the article is to report the case of a 20-year-old patient with a threatened
      aortic injury from pedicle screw instrumentation successfully managed without
      aortic grafting. Methods The patient's clinical course is retrospectively
      reviewed. The offending hardware was removed after gaining endovascular control
      of the aorta. Results Intraoperative aortography was normal and no graft was
      placed. The patient remains asymptomatic at 2 years after surgery. Conclusions
      Hardware impinging on the aorta can safely be removed by gaining endovascular
      control of the aorta. In the setting of normal intraoperative aortography in a
      young patient, we recommend against further intervention to avoid the known
      morbidity of aortic grafting. 

PMID- 24436715
TI  - Canine notochordal cell-secreted factors protect murine and human nucleus
      pulposus cells from apoptosis by inhibition of activated caspase-9 and caspase
      3/7.
AB  - Introduction Effective therapies that may stop or even reverse disc degeneration
      remain elusive. A minimally invasive method through which nucleus pulposus (NP)
      cell viability could be achieved would revolutionize the treatment of
      degenerative disc disease (DDD). With the presented work, we have investigated if
      nonchondrodystrophic (NCD) canine intervertebral disc (IVD)-derived notochordal
      cell conditioned medium (NCCM) and chondrodystrophic (CD) canine IVD-derived
      conditioned medium (CDCM) are able to protect murine and human NP cells from
      apoptosis. Materials and Methods We developed NCCM and CDCM from hypoxic culture
      of freshly isolated NPs from NCD and CD canines, respectively. We obtained murine
      NP cells from nine different C57BL/6 mice and human NP cells from four patients
      who underwent surgery for discectomy. The cells were cultured with ADMEM/F-12
      (control media), NCCM, or CDCM under hypoxic conditions (3.5% O2) and treated
      with IL-1beta + FasL or Etoposide. All media were supplemented with 2% fetal
      bovine serum. We then determined the expression of specific apoptotic pathways in
      the murine and human NP cells by recording activated caspase-8, caspase-9, and
      caspase-3/7 activity. Results In the murine NP cells, NCCM inhibits IL-1beta +
      FasL- and Etoposide-mediated apoptosis via suppression of activated caspase-9 and
      caspase-3/7, CDCM demonstrated an inhibitory effect on IL-1beta + FasL-mediated
      apoptosis via caspase-3/7 (Fig. 1A). In the human NP cells, NCCM inhibits
      Etoposide- mediated apoptosis via suppression of activated caspase-8, caspase-9,
      and mainly caspase-3/7. CDCM demonstrated an inhibitory effect on Etoposide
      mediated apoptosis via suppression of activated caspase-8, caspase-9, and mainly
      caspase-3/7, though not as effective as NCCM (Fig. 1B). Conclusion IL-1beta +
      FasL are known key molecules in the progression of DDD. Here, we demonstrate that
      soluble factors secreted by the NCD IVD NP strongly protect murine NP cells not
      only from IL-1beta + FasL but also from Etoposide-induced apoptosis via
      suppression of activated caspase-9 and caspase-3/7. In the human samples,
      addition of IL-1beta + FasL did not increase cell death. Because the human cell
      samples were obtained from herniated discs that are probably already undergoing a
      degenerative process, it is likely that there was already some degree of
      activation by the endogenously secreted prodegenerative factors such as IL-1beta
      + FasL. It may be that the NP cells, once they have reached a pivotal point of
      the degenerative cascade, no longer respond to exogenously applied IL-1beta +
      FasL in contrast to the otherwise "healthy" discs obtained from the mice.
      Interestingly, the rescue effect of NCCM in the etoposide-treated cells (murine
      and human) suggests that NCCM is capable of influencing the signaling pathways
      known to be relevant to etoposide-induced cell death. A better understanding and
      harnessing of the restorative powers of the notochordal cell could lead to novel
      cellular and molecular strategies for the treatment of DDD. 

PMID- 24436716
TI  - Complications and intercenter variability of three-column resection osteotomies
      for spinal deformity surgery: a retrospective review of 423 patients.
AB  - Study Type Retrospective review of a prospectively collected multicenter
      database. Introduction Three-column resection osteotomies (3CO), including
      pedicle subtraction osteotomies and vertebral column resections are performed for
      correction of sagittal deformity; however, they have high rates of reported
      complications. This study examined the incidence and intercenter variability of
      major intraoperative complications (IOC), postoperative complications (POC), and
      overall complications (IOC + POC) up to 6 weeks postoperation. Objective The aim
      of the study is to examine the incidence and intercenter variability of major
      complications associated with 3CO. Patients and Methods A retrospective review of
      patients with 3CO from eight different sites was performed. The incidence and
      types of complications were determined for the study population (N = 423). The
      analysis compared patients with one (n = 391) and two (n = 32) osteotomies, as
      well as patients with a thoracic osteotomy (ThO) (n = 72) versus a lumbosacral
      osteotomy (LSO) (n = 319) of the spine. Subsequent analysis was performed to
      compare sites with low-osteotomy volumes (< 50 patients) to sites with large
      osteotomy volumes (more than 50 patients). Major blood loss (MBL) was defined as
      more than 4L. Results Of the 423 patients, the incidence of major IOC, POC, and
      overall complications was 28, 45, and 58%, respectively (Table 1). The most
      common major IOC was MBL (24%) and the most common POC was unplanned return to
      the operating room (OR) (19%). Other IOC included cord deficit (2.6%),
      pneumothorax (1.5%), large vessel injury (1.7%), nerve root injury (1.4%), and
      cardiac arrest (0.2%). Other POC included motor deficit (12.1%), deep infection
      (7.6%), acute respiratory distress/failure (4.7%), deep venous thrombosis (3.1%),
      pulmonary embolism (2.8%), arrhythmia (1.2%), reintubation and sepsis (0.7%),
      cauda equine syndrome, myocardial infarction, visual deficit, stroke (0.5%), and
      death (0.2%). Patients with one 3CO had significantly less POC (43 vs. 69%, p <
      0.01) and overall complications (57 vs. 75%, p < 0.01) than patients with two 3CO
      (Fig. 1). IOC, MBL, and return to the OR were not significantly different between
      groups. Patients with ThO had significantly more POC (66 vs. 39%, p < 0.01) and
      overall complications (76 vs. 53%, p < 0.001) than patients with LSO. Patients
      with LSO had more MBL (25 vs. 14%, p = 0.04). Patients with ThO had more
      unplanned return to OR (41 vs. 14%, p < 0.001) (Fig. 2). The incidence of IOC was
      greater for the low-volume sites than high-volume sites (46 vs. 23%, p < 0.001).
      Low-volume sites had a higher frequency of patients with MBL than high-volume
      sites (45 vs. 18%, p < 0.001) (Fig. 3). Patients who experienced MBL had a
      significantly longer operating time (p < 0.001) and a higher risk of developing
      other IOC, POC, and overall complications (OR = 2.18, 1.51, 1.63, respectively)
      than patients who did not experience substantial blood loss. Conclusions The
      overall incidence of complications was 58% following 3CO surgery. There was
      significant variation in incidence of complications depending on the number,
      location, and experience of performing osteotomies. Risks for developing
      complications included having two osteotomies, ThO, surgery at a low-volume
      center, and blood loss more than 4 L. With a better understanding of 3CO
      complications and risk factors, physicians may be more informed in the decision
      making process of sagittal plane deformity correction. 

PMID- 24436717
TI  - A novel scientific model for rare and often neglected neoplastic conditions.
AB  - Study Type Retrospective cohort. Introduction The treatment of rare neoplastic
      conditions is challenging, especially because studies providing high levels of
      evidence are often lacking. Such is the case with primary tumors of the spine
      (PTS), which have a low incidence, are pathologically heterogeneous, and have
      diverse treatment approaches.1 Despite these difficulties, appropriate evidence
      based care of these complex patients is imperative. Failure to follow validated
      oncologic principles may lead to unnecessary mortality and profound morbidity.
      Objective With the aim of offering patients the most appropriate treatment based
      on the best available evidence, a novel scientific model was developed and
      employed. This article outlines this model, which has not only provided
      significant evidence guiding treatment of this rare condition, but we believe is
      readily transferrable to other similarly rare conditions. Methods A four-stage
      approach was employed. (1) Planning: Data from large volume centers were reviewed
      together with results from a feasibility questionnaire to provide insight into
      epidemiology, patient volumes, tumor pathology, treatment modalities, and
      outcomes. (2) Recruitment: Centers with sufficient volume and valid data were
      enrolled and provided with the necessary infrastructure. This included study
      coordinators and a secure, Web-based database (REDCap, Vanderbilt University,
      Nashville, Tennessee, United States) to capture international data from six
      modules comprising: demographic, clinical, diagnostic, therapeutic, local
      recurrence, perioperative morbidity fields, and a cross-sectional survey to
      update survival information. The AOSpine Knowledge Forum Tumor designed these
      modules and provided funding. Each center received institutional ethics approval.
      (3) Retrospective stage: Prospectively collected data from all recruited centers
      were reviewed and analyzed retrospectively. (4) Prospective stage: Following
      interim analysis, prospective data collection has been implemented. In addition,
      a PTS bio-bank network has been created to link clinical data with tumor
      pathology and molecular analysis. Results It took 18 months to implement stages 1
      to 3 of this model and stage 4 is ongoing. A total of 1,495 tumor cases were
      captured and diagnosed as one of the 18 primary spine tumor subtypes listed (Fig.
      1). The most prevalent diagnosis was chordoma (n = 344, 23%). There were 674
      females and 821 males with a mean age of 43 +/- 19 years at the time of surgery.
      Surgical treatment was performed between 1981 and 2012. The survival at 5 and 10
      years postsurgery was 71.9 and 53.3%, respectively, with a median survival of 13
      years postsurgery (Fig. 2). Conclusions To date, this is the largest
      international collection of PTS. This novel scientific model has not only
      aggregated a large amount of PTS data, but has also established an international
      collaborative network of spine oncology centers. The access to large volumes of
      clinical and bio-bank data will generate further research to guide and enhance
      the clinical management of PTS. This novel scientific model could be of similar
      tremendous value if applied to other rare neoplastic conditions. 

PMID- 24436718
TI  - Early proximal junctional failure in patients with preoperative sagittal
      imbalance.
AB  - Study Type Retrospective review. Introduction Sagittal imbalance has been
      associated with lower health-related quality of life outcomes, and restoration of
      imbalance is associated with improved outcomes.123 The long constructs used in
      adult spinal deformity have potential consequences such as proximal junctional
      kyphosis (PJK). Clinically, the development of PJK may not be as important as
      failure of the construct or vertebrae at the proximal end. As PJK does not lead
      to worse clinical outcomes,45 we define the term early proximal junctional
      failure (EPJF) as fracture, implant failure, or myelopathy due to stenosis at the
      upper instrumental vertebra (UIV) or UIV + 1 within 6 months of surgery.
      Objective The purpose of this study is to report the incidence of EPJF in
      patients who are sagittally imbalanced preoperatively and to identify risk
      factors postoperatively that correlate with EPJF using commonly reported sagittal
      balance parameters. Methods We reviewed 197 patients with preoperative sagittal
      imbalance by at least one of the following: sagittal vertical axis more than 5
      cm, global sagittal alignment more than 45 degrees, pelvic incidence-lumbar
      lordosis more than 10 degrees, or spine-sacral angle less than 120 degrees.
      Radiographic measurements also included proximal junctional angle, thoracic
      kyphosis, lumbar lordosis, pelvic parameters, and sagittal balance
      parameters/formulas, as well as UIV angle, UIV spinosacral angle, and UIV plumb
      line to assess as potential risk factors. EPJF incidence was calculated
      postoperatively for each of the accepted sagittal balance parameters/formulas.
      Results EPJF was observed in 49 of 197 patients (25%) with preoperative sagittal
      imbalance and was more common in fusions with UIV in the lower thoracic spine
      (TS) (35%) than in those with UIV in the upper TS (10%) or lumbar (25%) (p =
      0.007). Of the 49 EPJF patients, 16 patients (33%) required revision surgery
      within the first year, for an overall early revision rate of 8%. The incidence of
      EPJF was no different in patients with or without postoperative sagittal balance.
      No parameter/formula was more sensitive than another in predicting EPJF.
      Conclusions The incidence of EPJF (25%) is greater in this sagittally imbalanced
      group than previously reported for adult deformity patients, occurring most often
      when the UIV is in the lower TS. Sagittal balance correction was not correlated
      with change in incidence of EPJF. Despite the high incidence, the early revision
      rate within the first year is low. 

PMID- 24436719
TI  - Comments on: Efficacy of Bracing versus Observation in the Treatment of
      Idiopathic Scoliosis (Evid Based Spine Care J 2011;2(2):25-34).

PMID- 24436721
TI  - Definition of Classes of Evidence (CoE) and Overall Strength of Evidence (SoE).

PMID- 24436720
TI  - Response to Letter to the Editor on: Efficacy of Bracing versus Observation in
      the Treatment of Idiopathic Scoliosis (Evid Based Spine Care J 2011;2(2):25-34).

PMID- 24436722
TI  - Medical Informatics and Opportunity for Anesthesiologists.

PMID- 24436723
TI  - Omega-3 fatty acids: An update emphasizing clinical use.

PMID- 24436724
TI  - Photolabile Amphiphiles with Fluorogenic Thioxanthone-Dithiane Functionality:
      Synthesis and Photoinduced Fragmentation in Micelles.
AB  - Novel photolabile amphiphiles containing thioxanthone-based fluorogenic caging
      groups are developed. Photoinduced fragmentation in dithiane-thioxanthone adducts
      was demonstrated to occur with 100% quantum efficiency at lambda ~ 320 nm and
      more than 50% at lambda ~ 360 nm. A plausible mechanism involves homolytic
      fission of a carbon-carbon single bond in the excited thioxanthone followed by
      disproportionation via hydrogen transfer. The critical feature of the system is
      that fluorescence of a substituted thioxanthone is recovered as a result of
      photofragmentation, making dithiane-thioxanthone adducts efficient fluorogenic
      caging groups. Photolabile amphiphiles containing these fluorogens are
      synthesized and their photoinduced disassembly is probed while following the
      fluorescence recovery. This methodology allows for destabilizing supramolecular
      assemblies of amphiphiles and at the same time offers a feedback mechanism for
      monitoring the process by fluorescence.

PMID- 24436725
TI  - Far-field Imaging of Non-fluorescent Species with Sub-diffraction Resolution.
AB  - Super-resolution optical microscopy is opening a new window to unveil the unseen
      details on the nanoscopic scale. Current far-field super-resolution techniques
      rely on fluorescence as the read-out1-5. Here, we demonstrate a scheme for
      breaking the diffraction limit in far-field imaging of non-fluorescent species by
      using spatially controlled saturation of electronic absorption. Our method is
      based on a pump-probe process where a modulated pump field perturbs the charge
      carrier density in a sample, thus modulating the transmission of a probe field. A
      doughnut shape laser beam is then added to transiently saturate the electronic
      transition in the periphery of the focal volume, thus the induced modulation in
      the sequential probe pulse only occurs at the focal center. By raster scanning
      the three collinearly aligned beams, high-speed sub-diffraction-limited imaging
      of graphite nano-platelets was performed. This technique potentially enables
      super-resolution imaging of nano-materials and non-fluorescent chromophores,
      which may remain out of reach for fluorescence-based methods.

PMID- 24436726
TI  - Use of Free-standing Filters in an Asthma Intervention Study.
AB  - This study characterizes the use of HEPA air filters provided to 89 households
      participating in an intervention study investigating the respiratory health of
      children with asthma. Freestanding filters were placed in the child's bedroom and
      monitored continuously for nearly a year in each household. Filter use was
      significantly affected by study phase, season and monitoring week. During the
      "intensive" weeks when a community education worker and a field technician
      visited the household, the use rate averaged 70+/-33%. During season-long "non
      intensive" periods between seasonal visits, use dropped to 34+/-30%. Filter use
      rapidly decreased during the 3 to 4 weeks following each intensive, was slightly
      higher in spring, summer, and in the evening and at night when the child was
      likely to be home, although households did not follow consistent diurnal
      patterns. While participants expressed an understanding of the benefits of filter
      use and reported good experiences with them, use rates were low, particularly
      during unobserved non-intensive periods. The provision of freestanding air
      filters to individuals or households must be considered an active intervention
      that requires monitoring and evaluation, otherwise unknown and unexpected
      patterns of filter use may alter and possibly bias results due to exposure
      misclassification.

PMID- 24436727
TI  - BAYESIAN SHRINKAGE METHODS FOR PARTIALLY OBSERVED DATA WITH MANY PREDICTORS.
AB  - Motivated by the increasing use of and rapid changes in array technologies, we
      consider the prediction problem of fitting a linear regression relating a
      continuous outcome Y to a large number of covariates X , eg measurements from
      current, state-of-the-art technology. For most of the samples, only the outcome Y
      and surrogate covariates, W , are available. These surrogates may be data from
      prior studies using older technologies. Owing to the dimension of the problem and
      the large fraction of missing information, a critical issue is appropriate
      shrinkage of model parameters for an optimal bias-variance tradeoff. We discuss a
      variety of fully Bayesian and Empirical Bayes algorithms which account for
      uncertainty in the missing data and adaptively shrink parameter estimates for
      superior prediction. These methods are evaluated via a comprehensive simulation
      study. In addition, we apply our methods to a lung cancer dataset, predicting
      survival time (Y) using qRT-PCR ( X ) and microarray ( W ) measurements.

PMID- 24436729
TI  - Frey's Syndrome Consequent to an Unusual Pattern of Temporomandibular Joint
      Dislocation: Case Report with Review of Its Incidence and Etiology.
AB  - Frey's syndrome was first described in the 18(th) century. Recognizing it as a
      nonspecific condition, the symptom of gustatory sweating in patients with parotid
      gland inflammation was described by Duphenix and Baillarger. However, as a
      specific diagnostic entity, gustatory sweating, following trauma to parotid
      glands, was first described by Polish neurologist Lucie Frey, in 1923, and hence
      he proposed the term auriculotemporal syndrome. The condition is characterized by
      sweating, flushing, a sense of warmth, and occasional pain in the preauricular
      and temporal areas, following the production of a strong salivary stimulus.
      Several etiologies of Frey's syndrome have been mentioned in the literature;
      however, none attribute dislocation of the "intact" mandibular condyle as a cause
      of the syndrome. Reviewing its pathophysiology, etiology, and incidence in
      detail, we describe a case of Frey's syndrome subsequent to superolateral
      dislocation of the intact mandibular condyle following fracture of the anterior
      mandible. Its management and prevention are also discussed in brief. 

PMID- 24436728
TI  - The social brain and reward: social information processing in the human striatum.
AB  - In the highly social life of humans, rewards that are sought and experienced are
      intertwined with social relationships and interactions between people. Just as we
      value nonsocial rewards such as food or money, we also value social outcomes
      (e.g., praise from a superior). We use social information to evaluate and form
      expectations of others and to make decisions involving others. Here we review
      research demonstrating how the neural circuitry of reward, particularly the
      striatum, is also involved in processing social information and making decisions
      in social situations. This research provides an understanding of the neural basis
      for social behavior from the perspective of how we evaluate social experiences
      and how our social interactions and decisions are motivated. We review research
      addressing the common neural systems underlying evaluation of social and
      nonsocial rewards. The human striatum, known to play a key role in reward
      processing, displays signals related to a broad spectrum of social functioning,
      including evaluating social rewards, making decisions influenced by social
      factors, learning about social others, cooperating, competing, and following
      social norms. WIREs Cogn Sci 2014, 5:61-73. doi: 10.1002/wcs.1266 Conflict of
      interest: The authors have declared no conflicts of interest for this article.
      For further resources related to this article, please visit the WIREs website.

PMID- 24436730
TI  - Pediatric orbital fractures.
AB  - It is wise to recall the dictum "children are not small adults" when managing
      pediatric orbital fractures. In a child, the craniofacial skeleton undergoes
      significant changes in size, shape, and proportion as it grows into maturity.
      Accordingly, the craniomaxillofacial surgeon must select an appropriate treatment
      strategy that considers both the nature of the injury and the child's stage of
      growth. The following review will discuss the management of pediatric orbital
      fractures, with an emphasis on clinically oriented anatomy and development. 

PMID- 24436731
TI  - Peculiarities of employment of polymeric miniplates for mandibular
      osteosynthesis: a preliminary study.
AB  - Searching for new materials for bone substitution, fixation, and reconstruction
      is a challenging task that attracts scientists and researchers of different
      fields of medicine. During the last few decades, much interest has been paid to
      polymeric materials, polyethylene in particular. The aim of this study is to
      present generalizations about our own experience in the employment of
      polyethylene miniplates for the surgical treatment of mandibular fractures.
      Ninety patients with 139 uni- and bilateral mandibular fractures in different
      locations were involved. Treatment modalities included open reduction and
      internal fixation with self-made polyethylene miniplates of straight, T-shaped, Y
      shaped, and X-shaped configurations and titanium screws. In 88 (97.8%) cases of
      surgical treatment of mandibular fractures using polymer miniplates, good
      anatomical and functional results were achieved. Regardless of the necessity for
      improvement of some mechanical properties of polyethylene, the results obtained
      in our clinical investigation allow us to recommend polyethylene miniplates for
      routine practice. 

PMID- 24436732
TI  - Use of 3-d plate in displaced angle fracture of mandible.
AB  - Introduction Mandibular angle fractures can be treated by various methods, but
      even the most popular methods may not be able to give satisfactory results, as
      the pterygomasseteric sling and masticatory forces can result in displaced angle
      fracture. These displaced fragments cannot be satisfactorily retained by single
      miniplate fixation. The aim of this study is to assess treatment of displaced
      angle fracture with 3-D miniplate fixation. This study can also be considered as
      a therapeutic study with level V evidence. Materials and Methods This study was
      designed to assess the feasibility of 3-D matrix miniplate fixation in displaced
      angle fractures. Eighteen patients with displaced angle fractures were included
      in this study. Matrix miniplate fixation was done transorally under general
      anesthesia. Results All these cases were treated successfully, and common
      complications like infection (5.5% of patients), wound dehiscence (11%),
      paresthesia (16.7%), and malocclusion (11%) were observed in our study.
      Conclusions Three-dimensional miniplate fixation in displaced angle fractures
      provides better stability and function. 

PMID- 24436733
TI  - Transfusion Requirements in Microsurgical Reconstruction in Maxillofacial
      Surgery: Ethical and Legal Problems of Patients Who Are Jehovah's Witnesses.
AB  - Objective To study transfusion requirements in patients with cancer undergoing
      head and neck reconstructive surgery and to discuss surgical and anesthetic
      strategies to reduce blood loss when the patient is a Jehovah's Witness. Material
      and Methods A descriptive study to expose the percentage of blood transfusions
      performed in patients with cancer undergoing microsurgical reconstructions in the
      department of oral and maxillofacial surgery of the referred hospital in the past
      9 years. Results Two hundred thirty-seven microsurgical reconstructions were
      performed in head and neck tumors between January 2001 and December 2009.
      Statistical analysis shows a significant decrease (p = 0.035) in the number of
      patients needing transfusions patients in recent years. Conclusions The treatment
      of patients who are Jehovah's Witnesses is an ethical and moral dilemma for the
      clinician and in particular for surgeons. 

PMID- 24436734
TI  - Maxillofacial fractures of pedestrians injured in a motor vehicle accident.
AB  - Maxillofacial fractures of pedestrians injured in a motor vehicle accident were
      retrospectively analyzed. The patients were 38 males and 26 females, and their
      age was distributed almost evenly from 1 to 91 years old (average 45.9 +/- 24.8
      years old). Motor vehicle collisions were with an automobile in 46 patients
      (71.9%), a motorcycle in 17 (26.6%), and a train in 1 (1.6%). The midface was
      involved in 32 patients (50.0%), the mandible in 19 (29.7%), and both the
      mandible and the midface in 13 (20.3%). Fractures were frequently observed in the
      zygoma and alveolus in the midface and in the condyle, symphysis, and body in the
      mandible. The facial injury severity scale (FISS) rating ranged from 1 to 9
      (average 2.30 +/- 1.79). Injuries to other sites of the body occurred in 29
      patients (45.3%). Observation was most frequently chosen in 26 patients (40.6%),
      followed by open reduction and internal fixation (ORIF) in 18 (28.1%), and
      maxillomandibular fixation (MMF) in 8 (12.5%). The FISS rating was higher in
      patients treated with ORIF and MMF. Injuries to other sites of the body were
      observed at a higher rate in patients who collided with an automobile and were
      also treated by ORIF. 

PMID- 24436735
TI  - Controversies in the satisfaction of surgeons and orthodontists on facial
      aesthetics after orthognathic surgery.
AB  - Aim Acceptable facial aesthetics is a common desire among patients presenting
      with dentofacial deformities planning to undergo orthognathic surgeries. Thus,
      professionals must be alert to their patients' complaints as well as their
      desires regarding facial morphology, because this is quite subjective and
      personal. This research aimed at evaluating the different views of orthodontists
      and oral maxillofacial surgeons regarding the facial analysis of patients who
      undergo orthognathic surgery. Methods Thirty individuals were selected with a
      minimum postoperative period of 6 months and photographed in the frontal and
      profile norm. Facial morphology characteristics were recorded to observe the
      agreement of the assessments of four professionals (two orthodontists and two
      surgeons). Results A significant agreement was seen between the orthodontists
      regarding the nasolabial angle (80%). In the frontal analysis, the agreement
      percentage (60%) between orthodontists and surgeons was considerable regarding
      facial asymmetry assessment. Conclusions Professionals must keep alert to facial
      analysis, especially in terms of tegumental harmony, for the orthognathic surgery
      to reestablish, satisfactorily, the facial aesthetics in all parameters set. 

PMID- 24436736
TI  - The Use of a Bioadhesive (BioGlue((r))) Secured Conchal Graft and Mandibular
      Distraction Osteogenesis to Correct Pediatric Facial Asymmetry as Result of
      Unilateral Temporomandibular Joint Ankylosis.
AB  - The rehabilitation of children affected by early traumatic facial deformity is a
      challenge for both the craniofacial team and the child's family. Although the
      immediate goals of surgery are to restore both form and function, the
      psychological needs of the growing child must also be addressed. Early surgery
      may be required to assist integration of the child into the community and thereby
      avert both social isolation and stigmatization of the child. Timed correctly,
      such surgery has the potential to harness the patient's own growth to assist in
      correction of the deformity and to maintain some of the surgical gains. The use
      of autogenous tissue rather than nondegradable implants to facilitate
      craniofacial reconstruction in the growing child avoids some of the concerns
      associated with permanent implants. These include both their potential to
      adversely affect growth and to migrate. The purpose of this article is to
      illustrate how advances in tissue adhesion using protein polymers (BioGlue((r));
      CryoLife, Inc., Kennesaw, GA) and bone regeneration techniques (distraction
      osteogenesis) have been used to correct the disfiguring and functional problems
      associated with unilateral temporomandibular joint ankylosis acquired in early
      childhood. 

PMID- 24436737
TI  - A Modified Kole's Osteotomy for Correction of Anterior Open Bite and Macrogenia
      in a Cleft Patient.
AB  - We present a modified technique to close anterior open bite as well as to correct
      anterior and vertical macrogenia without sacrificing the lowermost symphyseal
      segment, in comparison with conventional Kole's osteotomy, which can alter the
      symmetric bone architecture of the chin and jeopardize the blood supply of the
      sandwich segments. 

PMID- 24436738
TI  - Cosmetic Tattooing of Free Flaps following Head and Neck Reconstruction.
AB  - Free flap reconstruction of the head and neck is a widespread procedure. The
      aesthetic outcome is frequently compromised by color mismatch between the donor
      site skin and the complex pigmentation of the face. Various surgical procedures
      have been described to improve the appearance of external skin paddles. Medical
      tattooing is commonly used for nipple pigmentation in breast reconstruction and
      cosmetic procedures such as permanent makeup. This article describes the
      technique and its application to head and neck reconstruction. Medical tattooing
      can be used to improve the cosmetic appearance of head and neck free flaps. There
      is no donor site morbidity and subtle changes in color can be replicated. The
      article describes the technique of medical tattooing with the use of illustrative
      cases. Medical tattooing is a viable alternative for improving the appearance of
      cutaneous skin paddles following head and neck reconstruction with free flaps.
      Its advantages include no donor site morbidity, availability of an infinite range
      of colors, no requirement for general anesthesia, and the ability to use multiple
      colors in the one flap for complex pigmentation requirements. Its disadvantages
      include the need for specialized skills and equipment and the fading of color
      over time. 

PMID- 24436739
TI  - Innovative intraoperative titanium mesh preparation for safer implantation.
AB  - Titanium meshes have been extensively used in craniomaxillofacial surgery. The
      benefits of these titanium implants include being inert, stable, and radiopaque
      and having good drainage properties. The titanium mesh is cut to shape and bent
      before implantation, which may give rise to the cut edges being jagged and sharp.
      This can lead to soft tissue being caught or lacerated by these sharp ends. A
      change in technique to cut and shape the implant may reduce this problem. The
      implant should be cut right at the end of the bars flush with the remaining parts
      of the implant. We present a new and simple method for smoothing these
      troublesome edges. We use the diathermy scratch pad or tip cleaner, a tool used
      frequently in every major surgery. This scratch pad can be used as a rasp to
      smoothen the edges of the titanium mesh once it is cut into shape. 

PMID- 24436740
TI  - Endoscopic dacryocystorhinostomy.
AB  - External dacryocystorhinostomy was described in early 20th century. The
      introduction of nasal endoscopy and endoscopic sinus surgery in the 1980s paved
      the way for a transnasal endoscopic approach to lacrimal system. This article
      will review the indications and surgical techniques used for endoscopic
      dacryocystorhinostomy. 

PMID- 24436742
TI  - Utility of stereolithographic models in osteocutaneous free flap reconstruction
      of the head and neck.
AB  - Background Stereolithographic (SLA) models have become a valuable resource in
      preoperative planning in maxillofacial reconstruction. The objective of this
      study was to perform a defect specific analysis of the utility of SLA models. The
      goal was to determine the manner in which the perceived benefit of preoperative
      modeling translates to measurable clinical advantages. Methods Patients who
      underwent reconstruction of defects of the mandible or midface using SLA modeling
      between 2006 and 2011 were identified through billing records. Based on the
      nature and extent of bony defect, cases requiring nearly identical
      reconstruction, but without modeling, were matched case by case for comparison.
      Given the presumed efficiency of SLA modeling, a comparison of total and
      reconstructive operative times was performed to see if this could offset the cost
      of the model. Results There were 10 patients each in the "model" and "nonmodel"
      group. No significant differences were observed for total operative time between
      groups. Surprisingly, the total reconstructive time was lower in the group not
      using SLA models (p = 0.05). Conclusions SLA models provide several operative
      planning advantages, but did not appear to decrease operative time enough to
      sufficiently offset the cost of the model in this group. 

PMID- 24436743
TI  - Finite element analysis comparison of plate designs in managing fractures
      involving the mental foramen.
AB  - Introduction The aim of the study was to propose an ideal plating design for
      fractures running through the mental foramen. Methods The study compared three
      plating designs-two four-hole miniplates, 2 * 2-hole three-dimensional (3D)
      plate, and modified 2 * 2-hole 3D plate (posterior strut removed)-using finite
      element analysis. Von Mises stresses generated around the plates and bone were
      measured, as well as the mobility that is generated between the fracture
      fragments by applying muscle forces to generate bite force in one test and
      applying a force of 500 N over the premolars and first molar region in the second
      test. Results Von Mises stress in bone with miniplates measured 9.24 MPa in test
      1 and 131.99 MPa in test 2. The stress with unmodified 3D plates measured 34.9
      MPa in test 1 and150.03 MPa in test 2. The stress with modified 3D plates
      measured 24.98 MPa in test 1 and 150.59 MPa in test 2. Von Mises stress on the
      plates and screws measured 28.23 MPa, 95.97 MPa, 72.93 MPa in test 1 and 458.63
      MPa, 779.01 MPa, 742.39 MPa in test 2 on miniplates, unmodified 3D plates, and
      modified 3D plates, respectively. The fracture mobility generated in the model
      with miniplates measured 0.001 mm in test 1 and 0.01 mm in test 2 and 0.007 mm
      and 0.02 mm in the model with unmodified 3D plates in test 1 and in test 2,
      respectively. In the model with modified 3D plates, the value was 0.001 mm and
      0.01 mm in tests 1 and 2, respectively. Conclusion The ideal plate design is the
      two-plate technique with minimal stress generation on the bone and the hardware.
      The modified 3D plate has adequate strength to be used in the region but needs to
      be studied in detail. 

PMID- 24436741
TI  - Optic nerve monitoring.
AB  - Orbital and anterior skull base surgery is generally performed close to the
      prechiasmatic visual pathway, and clear strategies for detecting and handling
      visual pathway damage are essential. To overcome the common problem of a missed
      clinical examination because of an uncooperative or unresponsive patient, flash
      visual evoked potentials and electroretinograms should be used. These
      electrophysiologic examination techniques can provide evidence of intact,
      pathologic, or absent conductivity of the visual pathway when clinical assessment
      is not feasible. Visual evoked potentials and electroretinograms are thus
      essential diagnostic procedures not only for primary diagnosis but also for
      intraoperative evaluation. A decision for or against treatment of a visual
      pathway injury has to be made as fast as possible due to the enormous importance
      of the time elapsed with such injuries; this can be achieved additionally using
      multislice spiral computed tomography. The first-line conservative treatment of
      choice for such injuries is megadose methylprednisolone therapy. Surgery is used
      to decompress the orbital compartment by exposure of the intracanalicular part of
      the optic nerve in the case of optic canal compression. Modern
      craniomaxillofacial surgery requires detailed consideration of the diagnosis and
      treatment of traumatic visual pathway damage with the ultimate goal of preserving
      visual acuity. 

PMID- 24436744
TI  - Orbital floor reconstruction with free flaps after maxillectomy.
AB  - Background The purpose of this study is to evaluate the outcome of orbital floor
      reconstruction with free flaps after maxillectomy. Methods This was a
      retrospective analysis of 34 consecutive patients who underwent maxillectomy with
      orbital floor removal for malignancies, reconstructed with free flaps. A cross
      sectional survey to assess the functional and esthetic outcome was done in 28
      patients who were alive and disease-free, with a minimum of 6 months of follow
      up. Results Twenty-six patients had bony reconstruction, and eight had soft
      tissue reconstruction. Free fibula flap was the commonest flap used (n = 14).
      Visual acuity was normal in 86%. Eye movements were normal in 92%. Abnormal globe
      position resulted in nine patients. Esthetic satisfaction was good in 19 patients
      (68%). Though there was no statistically significant difference in outcome of
      visual acuity, eye movement, and patient esthetic satisfaction between patients
      with bony and soft tissue reconstruction, more patients without bony
      reconstruction had abnormal globe position (p = 0.040). Conclusion Free tissue
      transfer has improved the results of orbital floor reconstruction after total
      maxillectomy, preserving the eye. Good functional and esthetic outcome was
      achieved. Though our study favors a bony orbital reconstruction, a larger study
      with adequate power and equal distribution of patients among the groups would be
      needed to determine this. Free fibula flap remains the commonest choice when a
      bony reconstruction is contemplated. 

PMID- 24436745
TI  - Transoral Miniplate Fixation of Mandibular Angle Fracture with and without 2
      Weeks of Maxillomandibular Fixation: A Clinical Trial Study.
AB  - Background and Objectives The ideal line of osteosynthesis in mandibular angle
      fractures indicates that a plate might be placed either along or just below the
      external oblique ridge. Some authors believe that using one miniplate at this
      line at the mandibular angle region provides sufficient strength to stabilize the
      fracture but others imply a second plate is required. Such controversies exist in
      the use of maxillomandibular fixation (MMF). The intention of the present study
      was to compare efficiency and complications of using one miniplate with and
      without MMF in mandibular angle fractures. Methods and Materials Forty patients
      with facial trauma with mandibular angle fractures including displaced and
      unfavorable fractures were categorized into two groups of 20 persons. In all
      patients, one miniplate was placed on the external oblique ridge. In the first
      group, patients had light maxillomandibular elastic bands just after surgery but
      no rigid MMF. In the second group, patients had rigid MMF for 2 weeks after
      surgery. Patients were followed to evaluate complications and treatment
      efficiency. Conclusions Our study showed that use of a single miniplate in the
      external oblique ridge is a functionally stable treatment for all types of angle
      fractures (including displaced and unfavorable fractures) except comminuted and
      long oblique fractures, which were not included in our study. Use of
      postoperative MMF did not improve the results. 

PMID- 24436746
TI  - The thickness of parietal bones in a new zealand sample of cadaveric skulls in
      relation to calvarial bone graft.
AB  - Objectives To evaluate the average thickness of the parietal bones in their
      different regions to identify the ideal site(s) for calvarial bone graft harvest.
      Methods and Materials Thickness of the parietal bones of 25 wet cranial vaults of
      New Zealand European origin was measured in 135 different locations using an
      electronic caliper. Analyses to identify the ideal harvest sites were conducted
      so that the sites fit the features of an ideal harvest site described in the
      literature as: (1) 6 mm of minimum thickness and (2) 2 cm away from the midline.
      Results and Conclusion The overall average thickness was 6.69 +/- 0.22 mm. The
      average thickness at different sites within the same bone ranged from 2.85 to
      6.93 mm. In keeping with previous studies, the report observed a progressive
      thickening of the parietal bone in medial and posterior directions. Of the 135
      different locations measured, only 20% exceeded an average thickness of 6 mm as
      well as being 2 cm away from the sagittal midline. These locations were mainly
      located between 6 to 11 cm posterior to the coronal suture and 2 to 5 cm away
      from the sagittal suture. Conclusion Harvesting the calvarial bone graft in the
      area 6 to 11 cm posterior to the coronal suture and 2 cm away from the midline is
      recommended based on our study using cadaveric cranial vaults of New Zealand
      Europeans. 

PMID- 24436747
TI  - The role of fat grafting in the treatment of posttraumatic maxillofacial
      deformities.
AB  - Purpose The first autologous adipose tissue grafting was performed by Neuber in
      1893 with an open approach. In the early 1980s, Illouz and Fournier introduced
      closed liposuction. In the 1990s, Coleman published a new method of atraumatic
      fat transplantation. Recently, immunohistochemical studies of the extracellular
      matrix of the lipoaspirate showed the presence of adipose-derived stem cells. The
      purpose of this study is to describe the role of fat grafting in the management
      of posttraumatic facial deformities. Methods The study population was composed of
      all patients who underwent facial fat grafting between March 2008 and November
      2010 as a secondary reconstructive procedure after an initial unsatisfactory
      treatment of the skeletal fractures. We analyzed the postoperative morphological
      changes by comparing the grafted side of the face to the contralateral side with
      the aid of a software package. Results Nineteen patients were surgically treated
      with fat transplantation for facial asymmetry due to a pathological postoperative
      healing of the soft tissue. Clinical examination and software analysis showed
      adequate postoperative facial balance without major complications. Conclusion Fat
      grafting is a very powerful tool to correct posttraumatic maxillofacial
      deformities and to ensure a long-term follow-up. Although we have achieved
      excellent clinical results in our reconstructive clinical cases, we are convinced
      that more complex prospective studies, enriched by long-term radiological
      controls, are needed to fully understand the biological behavior of the
      transplanted fat in the posttraumatic face. 

PMID- 24436748
TI  - Midline mandibulotomy for reduction of long-standing temporomandibular joint
      dislocation.
AB  - Long-standing temporomandibular joint (TMJ) dislocation is an uncommon condition,
      and due to its rarity, no definitive guidelines have been developed for its
      management. Various reduction techniques ranging from indirect traction
      techniques to direct exposure of the TMJ have been used. Indirect traction
      techniques for reduction may fail in long-standing dislocation. Management of two
      cases of long-standing TMJ dislocation with midline mandibulotomy is discussed in
      which other indirect reduction techniques had failed. Midline osteotomy of the
      mandible can be used for reduction in difficult TMJ dislocations. An algorithm
      for the management of long-standing TMJ dislocation is proposed and related
      literature is reviewed. 

PMID- 24436749
TI  - Blowout fracture in a 3-year-old.
AB  - A 3-year-old patient was referred to the oral and maxillofacial department with a
      fracture of the orbital floor. Due to the lack of clinical symptoms, a
      conservative approach was chosen. After 3 weeks, an enophthalmos developed. The
      orbital floor reconstruction was successfully performed through a
      transconjunctival approach. This case highlights the rarity of pure blowout
      fractures in young children. The specific presentation and diagnostics of orbital
      floor fractures in children and the related surgical planning and intervention
      are discussed. 

PMID- 24436750
TI  - Mandible and Zygomatic Fracture in a 2-Year-Old Patient due to Dog Bite.
AB  - Dog bite injury frequently occurs in children, and many of these bites involve
      the facial region. On the other hand, facial fractures due to dog attacks are a
      rare complication, with the orbital, nasal, and maxillary bones most often
      affected. We present a case report of a child who suffered a double facial
      fracture, mandible and left zygoma, due to a dog bite. The clinical diagnosis was
      supported by X-rays and computed tomography, which also provided information
      about the characteristics of the fracture. Internal fixation was done with
      titanium miniplates. Finally, the pathophysiological mechanism and the
      biomechanics of the fracture, as well as the use of resorbable versus
      nonresorbable material on infants, are discussed. 

PMID- 24436751
TI  - Le fort I osteotomy with bone grafts in preprosthetic surgery: technical note.
AB  - Background Being edentulous causes progressive bony resorption in maxillae, which
      can lead to altered maxillomandibular relationships. Discussion should consider
      Le Fort I osteotomy with inlay grafts for a better success rate. Thus, this
      article introduces a technical note in improving the success rate. Case Report
      The presented technical note permits transformation of the surgery in a
      conventional Le Fort I with a simple fixation not only of the grafts but also of
      the osteotomy. The surgical steps are explained as well as the follow-up results.
      Discussion Adding additional wire anchorage around bone grafts greatly improved
      our success rate and reduced our operative time. Bone grafting concurrently with
      Le Fort I osteotomy immediately improved the facial skeletal profile. Several in
      vitro studies have shown that galvanic corrosion does not play a significant role
      when combining stainless steel and titanium. Our novel technique is relatively
      simple and can be easily picked up by young surgeons. 

PMID- 24436752
TI  - Pathologic fractures in bisphosphonate-related osteonecrosis of the jaw-review of
      the literature and review of our own cases.
AB  - Background Bisphosphonates are powerful drugs used for the management of
      osteoporosis and metastatic bone disease to avoid skeletal-related complications.
      Side effects are rare but potentially serious such as the bisphosphonate-related
      osteonecrosis of the jaws (BRONJ). BRONJ impairs the quality of life and can even
      lead to pathologic fractures of the mandible. Management of BRONJ is difficult
      per se. If complicated with pathologic mandibular fractures in advanced stages,
      the treatment options are controversially discussed. This review delineates the
      epidemiology and pathogenesis of BRONJ to put the various modalities for the
      treatment of pathologic mandible fractures into perspective. Methods Various case
      reports and case series in the literature were reviewed. Cases were reviewed of
      patients suffering from pathologic fracture due to bisphosphonate-related
      osteonecrosis of the jaw treated in the Department of Oral and Maxillofacial
      Surgery (Ludwig-Maximilians-University of Munich) from 2003 to 2010. Of 140
      patients suffering from BRONJ, four were identified with pathologic fracture of
      the mandible. Results Management of pathologic mandibular fractures in patients
      suffering from BRONJ is an unsolved issue. At present there is a paucity of
      information to establish reliable therapy guidelines. The published strategies
      range from conservative treatment to major bone resections with or without
      internal or external fixation and with or without autogenous reconstruction.
      There is no evidence for the superiority of a single therapeutic mode, however.
      Conclusion Further understanding of BRONJ is mandatory to establish a sound
      rationale for the treatment of associated mandibular fractures. 

PMID- 24436753
TI  - Frontal sinus fractures: a conservative shift.
AB  - This article reflects on the changing management of frontal sinus fractures.
      Severity of these injuries has decreased tremendously since the universal
      adoption of seat belts and air bags. Recently, there has been a shift from
      aggressive surgical management to more conservative management strategies, some
      forgoing surgery all together. New technologies, such as bioabsorbable plates and
      endoscopic sinus surgery, are leading the way in improved surgical management
      strategies and offer promising alternatives to the more traditional approaches. 

PMID- 24436754
TI  - Combined orbital floor and medial wall fractures involving the inferomedial
      strut: repair technique and case series using preshaped porous
      polyethylene/titanium implants.
AB  - Background Combined orbital floor and medial wall fractures can be technically
      challenging to repair, particularly when the inferomedial strut is involved. A
      surgical repair technique is described utilizing a single preshaped porous
      polyethylene/titanium implant to span both defects. Methods Retrospective
      interventional case series. Results Fracture repair was performed on 17 orbits
      (16 patients) between October 2009 and February 2012. Subsequent surgical
      revision was required in three cases (18%). Visual acuity was stable or improved
      in all cases. Of 7 patients with preoperative diplopia, 5 improved and 2 remained
      stable postoperatively, and there were no cases of new or worsened diplopia
      following surgery. Postoperative asymmetry in Hertel exophthalmometry averaged
      1.0 mm (range 0 to 2 mm). Preoperatively, average orbital volume was 122.7%
      compared with control (range 109 to 147%, standard deviation [SD] 9.6), which
      improved to 100.3% postoperatively (range 92 to 110%, SD 5.7). The average
      decrease in orbital volume was 22.5% (range 10 to 54%, SD 11.4, p < 0.001).
      Conclusions With careful preoperative planning and meticulous surgical technique,
      combined orbital floor and medial wall fractures involving the inferomedial strut
      can be successfully repaired with a preshaped porous polyethylene/titanium
      implant through a transconjunctival/transcaruncular approach with inferior
      oblique disinsertion. 

PMID- 24436755
TI  - Evaluation of temporomandibular joint total replacement with alloplastic
      prosthesis: observational study of 27 patients.
AB  - Background Temporomandibular joint (TMJ) total replacement with alloplastic
      prostheses has been performed since 1960s. Research in these last two decades has
      achieved important improvement in the development of biomaterials, design,
      adaptation, and fixation of the prosthesis components. Objective To evaluate
      total TMJ replacement with alloplastic prostheses. Methods We studied 27
      patients, between 19 and 73 years old, who had total TMJ uni- or bilateral
      replacement surgery with custom-made alloplastic prostheses manufactured by TMJ
      Concepts, Inc. (Ventura, CA) between 1996 and 2011. The general data and
      preoperative measurements were taken from medical records. Subjective data
      related to pain, diet consistency, and current quality of life were collected
      with a questionnaire answered by the patients; measures of maximum interincisal
      opening and lateral mandibular movements were obtained from direct examination.
      Results We found significant difference (p < 0.05) comparing pre- to
      postoperative results about improvement in mouth opening, pain relief, and
      satisfaction with the surgery and diet consistency. Conclusion The results of
      this study show that total alloplastic TMJ prostheses are an efficient, safe, and
      stable long-term solution for patients who need TMJ total replacement. 

PMID- 24436756
TI  - Sphenoid sinus and sphenoid bone fractures in patients with craniomaxillofacial
      trauma.
AB  - Background and Purpose Sphenoid bone fractures and sphenoid sinus fractures have
      a high morbidity due to its association with high-energy trauma. The purpose of
      this study is to describe individuals with traumatic injuries from different
      mechanisms and attempt to determine if there is any relationship between various
      isolated or combined fractures of facial skeleton and sphenoid bone and sphenoid
      sinus fractures. Methods We retrospectively studied hospital charts of all
      patients who reported to the trauma center at Hospital de San Jose with facial
      fractures from December 2009 to August 2011. All patients were evaluated by
      computed tomography scan and classified into low-, medium-, and high-energy
      trauma fractures, according to the classification described by Manson. Design
      This is a retrospective descriptive study. Results The study data were collected
      as part of retrospective analysis. A total of 250 patients reported to the trauma
      center of the study hospital with facial trauma. Thirty-eight patients were
      excluded. A total of 212 patients had facial fractures; 33 had a combination of
      sphenoid sinus and sphenoid bone fractures, and facial fractures were identified
      within this group (15.5%). Gender predilection was seen to favor males (77.3%)
      more than females (22.7%). The mean age of the patients was 37 years. Orbital
      fractures (78.8%) and maxillary fractures (57.5%) were found more commonly
      associated with sphenoid sinus and sphenoid bone fractures. Conclusions High
      energy trauma is more frequently associated with sphenoid fractures when compared
      with medium- and low-energy trauma. There is a correlation between facial
      fractures and sphenoid sinus and sphenoid bone fractures. A more exhaustive
      multicentric case-control study with a larger sample and additional parameters
      will be essential to reach definite conclusions regarding the spectrum of
      fractures of the sphenoid bone associated with facial fractures. 

PMID- 24436757
TI  - Evaluation of the Biodegradable Plates (PG910/PDO) for Reconstruction of Various
      Sizes of Orbital Floor Defects in the Blow-Out Fractures.
AB  - The aim of our study was to evaluate the biodegradable plates (PG910/PDO) for
      reconstruction of various sizes of the orbital floor defects in the blow-out
      fractures. We included patients who had an impure blow-out fracture. All patients
      had a recent trauma and also the surgical intervention was done between 1 and 10
      days after trauma. The amount of the orbital floor defect was measured in each
      case through computed tomography scan. In the surgical intervention, a
      biodegradable plate was used for the reconstruction of the orbital floor defect
      along with titanium miniplates used for bone fixation in orbital rim. Due to
      aesthetic reasons, all patients underwent secondary surgery including removal of
      titanium miniplates after 18 months. The orbital floor was reevaluated during the
      removal of the miniplates. The clinical evaluation of remnant defects and
      biodegradable plates (presence of complete or partial resorption) were documented
      for each patient. In our study a total of 15 patients (10 males and 5 females)
      underwent the orbital floor reconstruction using biodegradable miniplates. The
      size of the orbital floor defects was meanly 3.51 +/- 1.29 cm(2). Results
      demonstrated that 4 out of 15 patients had a remnant defect after resorption of
      the biodegradable plate. In 10 out of 15 patients, the biodegradable plates
      completely replaced with fibrous tissues after 18 months. Remaining five patients
      had partial resorption of plates. There was not any relationship between the
      defect size and the remnant defects (p > 0.05). A significant relationship was
      seen between the defect size and the plates' resorption rate (p < 0.001). There
      is a significant relationship between the resorption rate and the remnant defect.
      The risk to have remnant defects have been increased as the plates had incomplete
      resorption. The use of biodegradable plates is an appropriate option for
      reconstruction of the orbital floor defects. The defect size does not have any
      effect on the stability of the plate. However, incomplete plate resorption
      increases the risk of remnant defects in the orbital floor. The larger defects
      lead to slow degradation of biodegradable plates. 

PMID- 24436758
TI  - A Prospective Study of Strut versus Miniplate for Fractures of Mandibular Angle.
AB  - This prospective randomized clinical trial compared the treatment outcomes of
      strut plate and Champy miniplate in fixation of mandibular angle fractures.
      Patients with mandibular angle fracture were consented and enrolled into this
      study. Exclusion criteria include patients with severely comminuted fractures.
      The patients were randomly assigned to receive the strut plate or Champy
      miniplate for angle fracture fixation. Patient demographics, fracture
      characteristics, operative and postoperative outcomes were collected
      prospectively. Statistical analysis was performed to evaluate the significance of
      the outcome. A total of 18 patients were included in this study and randomly
      assigned to receive either the strut plate or Champy miniplate. Out of which five
      patients were excluded postoperatively due to complex fracture resulting in
      postoperative maxillomandibular fixation. The final enrollment was 13 patients, N
      = 6 (strut) and N = 7 (Champy). There was no statistically significant difference
      in the pretreatment variables. Nine of these patients had other associated facial
      fractures, including parasymphyseal and subcondylar fractures. Most of the (11)
      patients had sufficient follow-up after surgery. Both groups exhibited successful
      clinical unions of the mandibular angle fractures. The complications associated
      with the mandibular angle were 20% in the strut plate group and 16.7% in the
      Champy group. One patient in the strut plate group had a parasymphyseal
      infection, requiring hardware removal. The strut plate demonstrated comparable
      surgical outcome as the Champy miniplate. It is a safe and effective alternative
      for management of mandibular angle fracture. 

PMID- 24436759
TI  - Chronic suppurative osteomyelitis of mandible: a case report.
AB  - Osteomyelitis is an inflammatory disease of the bone that usually begins as an
      infection of the medullary cavity, rapidly involves the haversian system, and
      quickly extends to the periosteum of the area. It develops in the jaws after a
      chronic odontogenic infection or for a variety of other reasons such as trauma,
      inadequate treatment of fracture, or irradiation to the mandible. When
      antimicrobial agents or drainage prove unsuccessful, acute osteomyelitis may
      become chronic. Conventional radiography, culture, bone biopsy, radioisotope bone
      scan, laser Doppler flowmetry, computed tomography, and magnetic resonance
      imaging are used for its diagnosis. We present a case of chronic suppurative
      osteomyelitis associated with a draining extraoral sinus, which was successfully
      treated with surgical debridement and stabilization with a 10-hole reconstruction
      plate and bicortical screws using AO principles. 

PMID- 24436760
TI  - Pathologic fracture of the mandible secondary to traumatic bone cyst.
AB  - The traumatic bone cyst (TBC) is an uncommon and poorly understood lesion. First
      described in 1929, TBCs lack an epithelial lining, typically occur during the
      second decade of life, and are most frequently located in the jaw. Although the
      majority of TBCs are asymptomatic, rarely a TBC can cause a pathologic fracture
      of the mandible. We present a case of an adolescent suffering a sports-related
      pathologic mandible fracture secondary to a traumatic bone cyst. 

PMID- 24436761
TI  - Superolateral dislocation of bilateral intact condyles-an unusual presentation:
      report of a case and review of literature.
AB  - Dislocation of the mandibular condyle is the clinical condition of the condyle
      head being displaced out of the glenoid fossa but still remaining within the
      joint capsule. However, the anatomy of the mandibular condyle, glenoid fossa, and
      zygomatic arch usually prevent the dislocation of intact condyles out of the
      glenoid fossa whenever the mandible is subjected to high impact. Complete
      dislocation of the mandibular condyle from the glenoid fossa can be classified
      into four groups: anterior, posterior, lateral, and superior dislocation. All the
      groups except anterior dislocation are rare. Superolateral dislocation of the
      intact mandibular condyle occurs very rarely. We report a case of lateral
      dislocation of bilateral intact condyles associated with left parasymphysis
      fracture. The purpose of this report is to review all of the available English
      literature on this dislocation and discuss the possible causative mechanism and
      diagnostic features, as well as clinical management. 

PMID- 24436762
TI  - Simplified transoral load-bearing osteosynthesis with preformed mandible
      reconstruction plates.
AB  - Transcutaneous submandibular approaches are the preferred technique for the
      application of load-bearing mandibular osteosynthesis plates. However, an
      extraoral approach is associated with several shortcomings, like the risk of
      harming the facial nerve and scarring. This technical note presents a specialized
      mandibular reconstruction plate (MatrixMANDIBLE Preformed Reconstruction Plate
      [Synthes Maxillofacial, Paoli, PA]), simplifying the transoral application by its
      design with a preformed curvature along the lateral surface of the mandible. The
      application of wide-spanning plates reaching from the posterior margin of the
      ramus even into the contralateral body region is facilitated. Transoral
      application of preformed mandibular reconstruction plates seems to be a promising
      option to bypass external incisions and to reduce operating room time. 

PMID- 24436763
TI  - Screw-wire osteo-traction: an adjunctive or alternative method of anatomical
      reduction of multisegment midfacial fractures? A description of technique and
      prospective study of 40 patients.
AB  - Stable anatomical fracture reduction and segment control before miniplate
      fixation can be difficult to achieve in comminuted midfacial fractures. Fracture
      mobilization and reduction methods include Gillies elevation, malar hook, and
      Dingman elevators. No single method is used universally. Disadvantages include
      imprecise segment alignment and poor segment stability/control. We have employed
      screw-wire osteo-traction (SWOT) to address this problem. A literature review
      revealed two published reports. The aims were to evaluate the SWOT technique
      effectiveness as a fracture reduction method and to examine rates of revision
      fixation and plate removal. We recruited 40 consecutive patients requiring open
      reduction and internal fixation of multisegment midfacial fractures (2009-2012)
      and employed miniplate osteosynthesis in all patients. SWOT was used as a default
      reduction method in all patients. The rates of successful fracture reduction
      achieved by SWOT alone or in combination and of revision fixation and plate
      removal, were used as outcome indices of the reduction method effectiveness. The
      SWOT technique achieved satisfactory anatomical reduction in 27/40 patients when
      used alone. Other reduction methods were also used in 13/40 patients. No patient
      required revision fixation and three patients required late plate removal. SWOT
      can be used across the midface fracture pattern in conjunction with other methods
      or as a sole reduction method before miniplate fixation. 

PMID- 24436764
TI  - Utility of computed tomography scans in predicting need for surgery in nasal
      injuries.
AB  - In many centers, computed tomography (CT) scan is preferred over plain film
      radiographs in the setting of acute nasal injury because CT scan is thought to be
      more sensitive in predicting nasal bone fracture. However, the usefulness of CT
      scans in predicting the need for surgery in acute nasal injury has not been well
      studied. We conducted a retrospective review of 232 patients with known nasal
      bone fracture and found very similar rates of surgery in patients with a
      diagnosis of nasal fracture by CT scan as by nasal radiographs (41 and 37%,
      respectively). This suggests that experienced clinical examination remains the
      gold standard for determining the need for surgery in isolated nasal trauma,
      regardless of CT findings. 

PMID- 24436765
TI  - Analysis of pediatric facial dog bites.
AB  - The aim of this study was to characterize and report the epidemiological data
      regarding pediatric facial dog bites. For this study, a retrospective chart
      review was used. This study was performed at a large tertiary pediatric hospital.
      All children younger than 18 years who sought medical attention after a facial
      dog bite between January 1, 2003, and December 31, 2008, were included.
      Demographic and epidemiologic data were collected and analyzed. A total of 537
      children were identified. The average age was 4.59 +/- 3.36 years, with a slight
      male preponderance (52.0%). The majority of dog bites occurred in children 5
      years of age or younger (68.0%). Almost all (89.8%) of the dogs were known to the
      children. When circumstances surrounding the bite were documented, over half
      (53.2%) of the cases were provoked. The most common breeds were mixed breed
      (23.0%), Labrador retriever (13.7%), Rottweiler (4.9%), and German shepherd
      (4.4%). Inpatient treatment was required in 121 (22.5%) patients with an average
      length of stay of 2.96 +/- 2.77 days. Children 5 years or younger were more
      likely to be hospitalized than older children. Children 5 years old and younger
      are at high risk for being bitten in the face by a familiar dog and are more
      likely to require hospitalization than older children. Certain dog breeds are
      more likely to bite, and there is often a history of provocation. There is a
      tremendous financial and psychosocial burden associated with dog bites, and
      prevention strategies should focus on education with the aid of public policies
      and better documentation and reporting systems. 

PMID- 24436766
TI  - Tunneling technique for expedited fibula free tissue harvest.
AB  - Free fibula transfer can be associated with a slow and tedious dissection/harvest
      due to difficulty in visualizing the deeper structures. The purpose of this
      article is to review the first author's (Y.D.) experience with a novel technique
      for expedited harvest of fibula free flaps for mandibular reconstruction. A
      retrospective chart review was performed using the first author's clinical
      practice using chart data from September 1997 to August of 2007. All patients
      with available chart data who had undergone free fibular transfer for
      oromandibular reconstruction were included in this study. Charts that met the
      specified inclusion criteria were reviewed for patient demographic information,
      reason for free tissue transfer, flap loss rates (partial and total) and reasons
      for flap loss, average fibula harvest time (tourniquet time), and foot and ankle
      function postoperatively. During this time, a total of 283 fibula free flaps were
      performed in 276 patients. The average fibula harvest time (tourniquet time) for
      all cases was 22.6 minutes, with a range of 14 to 29 minutes. A total of 13 flaps
      were unsuccessful (failure rate of 4.6%, with 5 total and 8 partial flap losses).
      This newly described technique will allow for expedited and simplified harvest of
      fibula free flaps. 

PMID- 24436767
TI  - Nasofrontal outflow tract visibility in computed tomography imaging of frontal
      sinus fractures.
AB  - The choice of frontal sinus fracture treatment is based on multiple factors, one
      of which is injury to the nasofrontal outflow tract (NFOT). Computed tomography
      (CT) imaging of the NFOT can play an important role in the decision process. We
      sought to assess the visibility of the NFOT on CT scans in frontal sinus
      fractures. Patients with frontal sinus fractures (including the posterior table)
      receiving a CT scan from April 1st 2001 to December 31st 2009 were included.
      Scans were retrospectively assessed for available views (axial, coronal, and
      sagittal), slice thickness, inclusion of the anatomical NFOT region in the
      scanned area, and visibility of the NFOT. A total of 170 patients were included.
      In majority (71%) of patients NFOT was visible on one or more views, whereas in
      33% (N = 56) of patients had three complete views (complete anatomical NFOT
      region scanned in three views). In this subgroup, the ability to assess the NFOT
      increased to 89%. When selecting patients with three complete views of <= 2 mm
      slice thickness (N = 47), the ability to assess the NFOT increased to 96%. In
      conclusion, when assessing the NFOT using CT imaging, having three complete views
      (axial, coronal, and sagittal) and a <= 2 mm slice thickness greatly increases
      the NFOT visibility. 

PMID- 24436768
TI  - Ratio of Simple versus Comminuted Lateral Wall Fractures of the Orbit.
AB  - Reduction of a fracture may be relatively easy with a simple, noncomminuted
      fracture along the zygomaticofrontal suture, zygomaticomaxillary buttress, or the
      inferior rim of the orbit. When one or more of these key landmarks is comminuted,
      it becomes more important to confirm that the fracture commonly seen between the
      greater wing of the sphenoid and the zygoma is properly repositioned. The
      zygomaticosphenoidal suture is an excellent landmark with a simple lateral
      orbital wall fracture (LOWF), but it may not be reliable in patients with a
      comminuted fracture. The purpose of this study is to determine the frequency that
      the lateral orbital wall (LOW) is a reliable landmark in the reduction of a
      zygoma fracture by determining the ratio between simple versus comminuted LOWF.
      To identify 100 patients with a LOWF, the authors reviewed consecutive midface
      computed tomography images of 877 patients performed over a 25-month period from
      one of our city's primary Level I trauma and teaching hospitals. A total of 121
      LOWF were identified in 100 patients. In 60.3% of cases the facture was a simple,
      noncomminuted LOWF. In 39.7% of cases the fracture was comminuted (p = 0.023).
      Simple LOWF are significantly more common than comminuted fractures. In 39.7% of
      fractures the LOW is comminuted. This suggests that there are many fractures in
      which other modalities may be much more important to use to confirm the proper
      reduction of the zygoma. 

PMID- 24436769
TI  - Assessment of masticatory function using bite force measurements in patients
      treated for mandibular fractures.
AB  - Bite force measurements are excellent criteria for assessment of masticatory
      efficiency. The purpose of this study was to assess the effect of mandibular
      fractures on the bite forces of patients treated for such fractures. Patients who
      were surgically treated for isolated mandibular fractures in the Department of
      Oral and Maxillofacial Surgery from January 2006 to December 2007 were included
      in the study. Patients were asked to bite on a bite force transducer on the
      first, fourth, sixth, and ninth postoperative weeks. The bite force values were
      compared with those of age, sex, and weight-matched controls. A total of 60
      patients were included in the study. It was found that maximum bite forces in
      patients were significantly less than in controls for several weeks after
      surgery. After the ninth postoperative week, the maximum bite force measured <
      65% the normal in patients with isolated angle fractures and > 80% the normal in
      patients with isolated parasymphysis fractures. The same values reduced to < 60%
      in patients with fractures of angle and parasymphysis and < 70% in patients with
      fractures of parasymphysis and condylar complex. An inverse relationship was
      found between the bite force values and the number of fractures of the mandible.
      We also found lower bite forces and longer period for normalization in patients
      who had fractures in those regions of the mandible which are more significantly
      associated with the masticatory apparatus for example angle or condyle of the
      mandible. 

PMID- 24436770
TI  - Branching pattern of the extraosseous mental nerve in a kenyan population.
AB  - Knowledge of the branching pattern of the mental nerve is an important
      consideration during placement of tooth implants and reconstructive plates. It is
      known to display population variations and data for the same is scarce form the
      sub-Saharan region. With the recent increase in surgical interventions in the
      mandibular region in Kenya, a detailed description of mental nerve is warranted.
      A total of 64 mental nerves were dissected and branching pattern was noted.
      Single mental nerve was present in 60 (93.7%) cadavers while double mental nerves
      occurred in 3 (4.7%) and accessory in 1(1.6%). Most common pattern was
      bifurcation (39%) followed by trifurcation (34%), single (19%), and
      quadrification (8%). The double and triple branches were seen to further divide
      into two to three subbranches with diverse patterns. Side symmetry in branching
      was seen in four (6.25%). These are important anatomical considerations during
      placement of reconstructive plates for mandibular trauma and administration of
      mental nerve blocks. 

PMID- 24436771
TI  - Complication of anterior iliac bone graft harvesting in 372 adult patients from
      may 2006 to may 2011 and a literature review.
AB  - Autogenous bone graft from the iliac is considered the gold standard graft
      material in maxillofacial surgery. The common and the rare complications
      associated with harvesting bone from anterior iliac crest were reviewed; we
      recommend a safe technique to avoid these complications. A retrospective analysis
      of 372 adult patients who had undergone anterior iliac bone graft harvesting from
      May 2006 to May 2011. The patients age range from 21 to 63 years. Out of the 372
      patients, 200 were male with age range from 21 to 63 years and 172 were female
      with age range from 22 to 59 years. Two major complications (fracture and seroma)
      occurred, a fracture of the anterior superior iliac spine was observed in two
      patients (0.538%); one male and one female. One female patient (0.269%) developed
      seroma. One minor complication occurred in three patients (0.806%); one female
      and two females who suffered from temporary sensory disturbance. All patients
      (100%) suffered pain maximum for the first 15 days postoperative. In our study;
      the morbidity after anterior iliac bone graft harvesting was found to be low due
      to the technique, utilizing the proper instruments, gentle and minimal
      mobilization of the graft. 

PMID- 24436772
TI  - Facial gel complication after dental injection: a case report.
AB  - Injectable gel is becoming increasingly popular for cosmetic reasons. The
      polyacrylamide gel (PAAG) is a permanent filler material used worldwide. In spite
      of the fact that the filler materials used today are considered quite safe,
      various complications have been reported in the literature. Hence PAAG use in the
      United States is not popular. As the area is very close to the dental field, a
      large complication potential is relatively considered following buccal dental
      injections. The aim of this article is to highlight a rare complication observed
      following a local anesthetic administration of a simple molar restoration in a
      healthy 33-year-old woman who had history of a filler augmentation in her cheek
      approximately 6 years ago. 

PMID- 24436773
TI  - Pseudoaneurysm of the internal maxillary artery: a rare complication of condylar
      fracture.
AB  - Pseudoaneurysms are among very rare complications of maxillofacial trauma. When
      encountered, they have the potential to cause life-threatening hemorrhage. A wise
      surgeon should consider the possibility of underlying aneurysm even if the
      classic sign of pulsatile mass is not present. The role of interventional
      radiology is immaculate in the management of these aneurysms. 

PMID- 24436774
TI  - Use of a Three-Dimensional Model to Optimize a MEDPOR Implant for Delayed
      Reconstruction of a Suprastructure Maxillectomy Defect.
AB  - The use of a three-dimensional (3-D) model has been well described for
      craniomaxillofacial reconstruction, especially with the preoperative planning of
      free fibula flaps. This article reports the application of an innovative 3-D
      model approach for the calculation of the exact contours, angles, length, and
      general morphology of a prefabricated MEDPOR 2/3 orbital implant for
      reconstruction of a suprastructure maxillectomy defect. The 3-D model allowed
      intraoperative modification of the MEDPOR implant which decreased the risk of
      iatrogenic harm, contamination while also improving aesthetic results and
      function. With the aid of preoperative 3-D models, porous polypropylene facial
      implants can be contoured efficiently intraoperatively to precisely reconstruct
      complex craniomaxillofacial defects. 

PMID- 24436775
TI  - Use of a mandibular plate to maintain intergonial width in a partially edentulous
      patient undergoing mandibular symphysis reconstruction.
AB  - One of the most challenging and essential aspects of management of patients with
      traumatic or ablative deformities involving the mandibular symphysis is
      maintenance of intergonial width. Classically, the use of occlusal splints has
      been a simple and cost-effective solution to this problem. Patients who are
      edentulous, the use of Gunning splints with circummandibular wires is an
      alternative strategy. In the present report, we describe the use of a mandibular
      fixation plate for maintenance of intergonial width in an edentulous patient with
      a postablative mandibular symphysis defect. 

PMID- 24436776
TI  - A Generalized Continual Reassessment Method for Two-Agent Phase I Trials.

PMID- 24436777
TI  - Is NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein-Protein
      Interactions?
AB  - Modulation of protein-protein interactions (PPIs) with small molecules has been
      hampered by a lack of lucid methods capable of reliably identifying high-quality
      hits. In fragment screening, the low ligand efficiencies associated with PPI
      target sites pose significant challenges to fragment binding detection. Here, we
      investigate the requirements for ligand-based NMR techniques to detect rule-of
      three compliant fragments that form part of known high-affinity inhibitors of the
      PPI between the von Hippel-Lindau protein and the alpha subunit of hypoxia
      inducible factor 1 (pVHL:HIF-1alpha). Careful triaging allowed rescuing weak but
      specific binding of fragments that would otherwise escape detection at this PPI.
      Further structural information provided by saturation transfer difference (STD)
      group epitope mapping, protein-based NMR, competitive isothermal titration
      calorimetry (ITC), and X-ray crystallography confirmed the binding mode of the
      rescued fragments. Our findings have important implications for PPI druggability
      assessment by fragment screening as they reveal an accessible threshold for
      fragment detection and validation.

PMID- 24436778
TI  - Highly Potent, Chemically Stable Quorum Sensing Agonists for Vibrio Cholerae.
AB  - In the Vibrio cholerae pathogen, initiation of bacterial quorum sensing pathways
      serves to suppress virulence. We describe herein a potent and chemically stable
      small molecule agonist of V. cholerae quorum sensing, which was identified
      through rational drug design based on the native quorum sensing signal. This
      novel agonist may serve as a useful lead compound for the control of virulence in
      V. cholerae.

PMID- 24436779
TI  - Effectiveness of cognitive behavioral therapy: An evaluation of therapies
      provided by trainees at a university psychotherapy training center.
AB  - At the psychotherapy training center at Karlstad University, a study was carried
      out to examine the levels of symptom change and satisfaction with therapy in a
      heterogeneous population of clients treated using cognitive behavioral therapy
      (CBT) by less experienced trainee therapists with limited theoretical education.
      The clients received an average of 11 therapy sessions. The results suggested
      that CBT performed by less experienced trainee therapists can be effective.
      According to client estimations, a statistically significant reduction in
      symptoms, measured using the Symptoms Checklist, was achieved for seven of nine
      variables (p <= .006), as well as a significant increase in satisfaction with
      life (p <= .001). Also, the pre- and posttherapy measurements using the
      Montgomery-Asberg Depression Rating Scale showed a statistically significant
      improvement in the clients' condition. According to the therapists' estimations,
      64% (SD = 32.01) of the clients experienced a significant improvement in their
      condition. In addition, the results of a survey of client satisfaction
      demonstrated that the clients were very pleased with the therapy received. Also
      the therapists were, to a great extent, satisfied with the treatment process
      itself, including the supervision received, and very satisfied with the client
      alliance. A correlation analysis between the clients' perceived level of
      improvement and therapist satisfaction showed a strong correlation between the
      two variables (r = .50, p < .005). By including the Comparative Psychotherapy
      Process Scale (CPPS) in our study it was possible to measure trueness to therapy
      form. An analysis of the CPPS results confirmed that the form of therapy used at
      the training site was more strongly CBT than psychodynamic interpersonal
      treatment (p <= .001). The CBT subscale score indicated that the therapy was
      characteristic of CBT, confirming that the interventions used in the therapy
      belong to the CBT genre.

PMID- 24436780
TI  - Titanium Dioxide Nanofibers and Microparticles Containing Nickel Nanoparticles.
AB  - The present study reports on the introduction of various nanocatalysts containing
      nickel (Ni) nanoparticles (NPs) embedded within TiO2 nanofibers and TiO2
      microparticles. Typically, a sol-gel consisting of titanium isopropoxide and Ni
      NPs was prepared to produce TiO2 nanofibers by the electrospinning process.
      Similarly, TiO2 microparticles containing Ni were prepared using a sol-gel
      syntheses process. The resultant structures were studied by SEM analyses, which
      confirmed well-obtained nanofibers and microparticles. Further, the XRD results
      demonstrated the crystalline feature of both TiO2 and Ni in the obtained
      composites. Internal morphology of prepared nanofibers and microparticles
      containing Ni NPs was characterized by TEM, which demonstrated characteristic
      structures with good dispersion of Ni NPs. In addition, the prepared structures
      were studied as a model for hydrogen production applications. The catalytic
      activity of the prepared materials was studied by in situ hydrolysis of NaBH4,
      which indicated that the nanofibers containing Ni NPs can lead to produce higher
      amounts of hydrogen when compared to other microparticles, also reported in this
      paper. Overall, these results confirm the potential use of these materials in
      hydrogen production systems.

PMID- 24436781
TI  - "Alas poor Yorick": What retrospective analysis of canine skulls can tell us
      about the impact of environmental factors on health.
AB  - Necropsies and extensive histological evaluation for clinical and sub-clinical
      disease of approximately three hundred Portuguese Water dogs are available as
      part of an ongoing study to assess their state of health at end of life.
      Throughout life these dogs enjoyed a variety of lifestyles and environments. Here
      we carry out retrospective quantitative assessments of life-time dietary input
      and physical activity for each dog. To do this, collagens from skull vault bone
      and from dentine have been analyzed for ratios of stable isotopes to determine
      differences in diet that individual dogs experienced during late or early life
      respectively. Robustness of skull bone (weight/unit of skull size) was used as a
      relative indicator of the amount of physical activity experienced during a dog's
      lifetime. These environmental parameters were correlated with the frequency and
      severity of specific disease processes determined at necropsy. Both measures were
      shown to exert significant low-level (r < 25%) differential effects on specific
      diseases. The value of retrospective analysis of environmental influences is
      discussed.

PMID- 24436782
TI  - Outcomes assessment in wrist surgery.

PMID- 24436783
TI  - Understanding wrist mechanics: a long and winding road.

PMID- 24436784
TI  - Resection interposition arthroplasty for failed distal ulna resections.
AB  - The major complications of distal ulna resection, the Darrach procedure, are
      radioulnar impingement and instability. High failure rates have been reported
      despite published modifications of the Darrach procedure. Several surgical
      techniques have been developed to treat this difficult problem and to mitigate
      the symptoms associated with painful convergence and impingement. No technique
      has demonstrated clinical superiority. Recently, implant arthroplasty of the
      distal ulna has been endorsed as an option for the management of the symptomatic
      patient with a failed distal ulna resection. However, there are concerns for
      implant longevity, especially in young, active adults. Resection interposition
      arthroplasty relies on interposition of an Achilles tendon allograft between the
      distal radius and the resected distal ulna. Although this technique does not
      restore normal mechanics of the distal radioulnar joint, it can prevent painful
      convergence of the radius on the ulna. Achilles allograft interposition
      arthroplasty is a safe and highly effective alternative for failed distal ulna
      resections, especially for young, active patients, in whom an implant or
      alternative procedure may not be appropriate. 

PMID- 24436785
TI  - Radiographic parameter analysis on modified sauve-kapandji procedure.
AB  - Purpose The Sauve-Kapandji (S-K) procedure is now an established treatment option
      for symptomatic distal radioulnar joint (DRUJ) dysfunction. However, for patients
      with poor bone quality (frequently as a result of advanced-stage rheumatoid
      arthritis [RA]), the conventional S-K procedure is difficult to perform without
      reducing the radioulnar diameter of the wrist, which may result in a loss of grip
      strength and pain over the proximal ulnar stump. The purpose of this study was to
      review the radiographic outcomes of patients who underwent a modified S-K
      procedure that involves rotating the resected ulnar segment 90 degrees and using
      it to bridge the gap between the sigmoid notch and the ulnar head. Methods The
      modified S-K procedure was performed in 29 wrists of 23 patients. Twenty-one
      patients had severe RA, while two had malunited radius fractures. The mean follow
      up period was 43 months (range, 23 to 95). The radiographic evaluation included a
      measurement of the radioulnar width, the pseudarthrosis gap between the proximal
      and distal ulnar stump, the radioulnar distance, and the ulnar translation of the
      carpus. Results The radioulnar width of the wrist, pseudarthrosis gap, and
      radioulnar distance were well maintained throughout the period. A postoperative
      loss in the radioulnar width of the wrists appeared to correlate with a
      postoperative additional ulnar translocation of the carpus. Conclusion Narrowing
      of the radioulnar width of the wrist is a potential cause of progressive ulnar
      translocation of the carpus. The modified technique for the S-K procedure
      maintains the distal ulna in the proper position and provides sufficient ulnar
      support for the carpus. It is a useful reconstruction procedure in patients with
      severe RA with poor bone quality. 

PMID- 24436786
TI  - Ulnar head replacement and related biomechanics.
AB  - A stable distal radioulnar joint (DRUJ) is mandatory for the function and load
      transmission in the wrist and forearm. Resectional salvage procedures such as the
      Darrach procedure, Bowers arthroplasty, and Sauve-Kapandji procedure include the
      potential risk of radioulnar instability and impingement, which can lead to pain
      and weakness. Soft tissue stabilizing techniques have only limited success rates
      in solving these problems. In an attempt to stabilize the distal forearm
      mechanically following ulnar head resection, various endoprostheses have been
      developed to replace the ulnar head. The prostheses can be used for secondary
      treatment of failed ulnar head resection, but they can also achieve good results
      in the primary treatment of osteoarthritis of the DRUJ. Our experience consists
      of twenty-five patients (follow-up 30 months) with DRUJ osteoarthritis who were
      treated with an ulnar head prosthesis, with improvement in pain, range of motion,
      and grip strength. An ulnar head prosthesis should be considered as a treatment
      option for a painful DRUJ. 

PMID- 24436787
TI  - The sauve-kapandji procedure.
AB  - Arthrodesis is the most reliable and durable surgical procedure for the treatment
      of a joint disorder, and its only disadvantage is the loss of motion of the fused
      joint. The distal radioulnar joint can be arthrodesed, while forearm pronation
      and supination are maintained or even improved by creating a pseudoarthrosis of
      the ulna just proximal to the arthrodesis. This is known as the Sauve-Kapandji (S
      K) procedure. The Sauve-Kapandji differs from the Darrach procedure in that it
      preserves ulnar support of the wrist, as the distal radioulnar ligaments and
      ulnocarpal ligaments are maintained. Aesthetic appearance is also superior after
      the S-K procedure, as the normal prominence of the ulnar head, most noticeable
      when the forearm is in pronation, is maintained. However, the S-K is not free of
      possible complications, such as nonunion or delayed union of the arthrodesis,
      fibrous or osseous union at the pseudoarthrosis, and painful instability at the
      proximal ulna stump. All of these complications can be prevented if a careful
      surgical technique is used. 

PMID- 24436788
TI  - Semiconstrained distal radioulnar joint prosthesis.
AB  - Distal radioulnar joint (DRUJ) problems can occur as a result of joint
      instability, abutment, or incongruity. The DRUJ is a weight-bearing joint; the
      ulnar head is frequently excised either totally or partially, and in some cases
      it is fused, because of degenerative, rheumatoid, or posttraumatic arthritis.
      Articles about these procedures report the ability to pronate and supinate, but
      they rarely discuss grip strength, and even less do they address lifting
      capacity. We report the long term results of the first 35 patients who underwent
      total DRUJ arthroplasty with the Aptis DRUJ prosthesis after 5 years follow-up.
      Surgical indications were all causes of dysfunctional DRUJ (degenerative,
      posttraumatic, autoimmune, congenital). We recorded data for patient
      demographics, range of motion (ROM), strength, and lifting capacity of the
      operated and of the nonoperated extremity. Pain and functional assessments were
      also recorded. The Aptis DRUJ prosthesis, a bipolar self-stabilizing DRUJ
      endoprosthesis that restores forearm function, consists of a semiconstained and
      modular implant designed to replace the function of the ulnar head, the sigmoid
      notch of the radius, and the triangular fibrocartilage ligaments. The surgical
      technique is presented in detail. The majority of the patients regained adequate
      ROM and improved their strength and lifting capacity to the operated side. Pain
      and activities of daily living were improved. Twelve patients experienced
      complications, most commonly being extensor carpi ulnaris (ECU) tendinitis,
      ectopic bone formation, bone resorption with stem loosening, low-grade infection,
      and need for ball replacement. The Aptis total DRUJ replacement prosthesis is an
      alternative to salvage procedures that enables a full range of motion as well as
      the ability to grip and lift weights encountered in daily living activities. 

PMID- 24436789
TI  - Opening wedge osteotomy for distal radius malunion: dorsal or palmar approach?
AB  - Background There are various technical variations to consider when performing a
      corrective osteotomy of a distal radius malunion. We chose two of the more
      commonly reported techniques and compared the results of volar (palmar) osteotomy
      and fixation with dorsal osteotomy and fixation. Method Within a continuous
      cohort of patients who had undergone corrective osteotomy for a malunited Colles
      fracture, two groups could be identified retrospectively. In 8 patients a dorsal
      approach was used. A structural trapezoidal graft, subtending the amount of
      correction, was inserted into the osteotomy gap and stabilization was performed
      with a thin round-hole mini-fragment plate. In 14 patients a palmar approach and
      a palmar fixed-angle plate was used for correction of the malunion and for
      angular stable rigid fixation of the two fragments. The osteotomy gap was loosely
      filled with nonstructural cancellous bone chips. A retrospective comparison of
      the two groups was performed to see whether the outcome was affected by the use
      of either operative technique.The demographics, the preoperative amount of
      deformity, range of motion, pain, and force were comparable for both groups. All
      osteotomies healed without loss of correction. After a minimal follow-up of one
      year, radiographic appearance, objective functional parameters were assessed and
      subjective data (Disabilities of the Arm, Shoulder, and Hand [DASH] score and
      special pain and function questionnaire) obtained. Results These data did not
      show statistical difference for the two groups except for the amount of final
      wrist flexion. This parameter was significantly better in patients who had palmar
      approaches and fixed-angle plates. Conclusion Corrective osteotomies of distal
      radius malunions can be done in either way. It might result in some better
      flexion, if performed volarly. 

PMID- 24436790
TI  - Thumb carpometacarpal ligaments inside and out: a comparative study of
      arthroscopic and gross anatomy from the robert a. Chase hand and upper limb
      center at stanford university.
AB  - Purpose We propose to identify and correlate arthroscopic internal ligaments with
      external ligaments, providing an accurate roadmap for arthroscopic ligament and
      joint anatomy. Ligamentous laxity is considered an important risk factor in
      developing the common basilar arthritis of the thumb. Controversy exists as to
      the precise ligamentous anatomy of the thumb carpometacarpal (CMC) joint (CMC-I);
      description of the internal arthroscopic anatomy is limited. Methods We performed
      CMC-I joint arthroscopy using the 1-Ulnar (1U) and thenar portals in five
      cadavers, seeking to identify the following seven ligaments arthroscopically: the
      superficial anterior oblique ligament (sAOL), deep anterior oblique ligament
      (dAOL), ulnar collateral ligament (UCL), dorsal trapeziometacarpal ligament (DTM
      1), posterior oblique ligament (POL), dorsal central ligament (DCL), and dorsal
      radial ligament (DRL). After grading articular changes of the trapezium, we
      passed Kirschner wires (K-wires) (0.028) outside-in to mark the arthroscopic
      insertion of each ligament on the trapezium. Gross dissection was performed to
      confirm the wire placement; the anatomic identity and position of joint
      stabilizing ligaments, and the location of frequently used portals. Results The
      volar ligaments-the sAOL, dAOL, and UCL-were highly variable in their
      arthroscopic appearance and precise location. The sAOL is a thin veil of
      membranous tissue that variably drapes across the anterior joint capsule. The
      reported dAOL and UCL, in our study, correlated to a thickened portion of this
      veil around the volar beak and was not consistently identified with gross
      dissection. In contrast, the arthroscopic appearance and location of the dorsal
      ligaments-DTM-I, POL, DCL, and DRL-were consistent in all specimens. Conclusion
      Our study further defines and correlates the arthroscopic and external
      ligamentous anatomy of the CMC-I joint. 

PMID- 24436791
TI  - Translunate perilunate injuries-a spectrum of this uncommon injury.
AB  - Purpose To review a series of translunate perilunate dislocations to analyze the,
      mechanism of injury, diagnosis, management, and outcome. Methods A literature
      review and a survey of the International Wrist Investigators Workshop were
      performed to locate cases. Results Translunate perilunate injuries are rare.
      There is a spectrum of severity. The mechanism of injury is usually high-energy,
      and multiple fractures are the norm. High-energy mechanism, perilunate
      dislocation, comminuted lunate fracture and delayed presentation greater than 7
      days are associated with a higher likelihood of a salvage procedure being
      required. Discussion Translunate injuries are a complex variant of perilunate
      dislocations. Early diagnosis is critical in understanding the complexity of the
      injury. Lunate fixation should be performed prior to bony and ligamentous
      stabilization of the proximal row. In delayed or highly comminuted cases, salvage
      procedures are the preferred option. Including a translunate arc in addition to
      the greater and lesser carpal arc would lead to a more inclusive classification.
      Level of Evidence Level IV. 

PMID- 24436792
TI  - The value of 3.0-tesla MRI in diagnosing scapholunate ligament injury.
AB  - Objective To determine the sensitivity and specificity of 3.0-tesla (T) magnetic
      resonance imaging (MRI) and a dedicated hand coil in diagnosing scapholunate
      ligament (SLL) injury compared with intraoperative findings. Methods From January
      2006 until September 2010, 3.0-T MRI scans were performed on 38 wrists (37
      patients) with clinically unclear but suspected lesions of the SLL. These scans
      were evaluated by two experienced radiologists. Radiological findings were
      compared with intraoperative findings during arthrotomy. Sensitivity,
      specificity, accuracy, and positive and negative predictive value were
      calculated. Results An SLL lesion was identified during arthrotomy in 37 wrists.
      The first radiologist identified an SLL lesion on MRI in 26 wrists, all of which
      were confirmed intraoperatively. The second radiologist identified SLL lesions in
      31 patients; however, intraoperatively it was found that there was no lesion of
      the ligament in one patient. Sensitivity ranged from 70 to 81% with a specificity
      of 100% and a positive predictive value of 97 to 100%. Accuracy measured 71 to
      79%. Conclusions 3.0-T MRI of the wrist is moderately sensitive and very specific
      for detection of SLL lesions. However, if there is a high clinical suspicion of
      an SLL rupture, a 3.0-T MRI does not often have an additional value. Level of
      Evidence Diagnostic, level II. 

PMID- 24436793
TI  - Chronic scaphoid nonunion of 28-year duration treated with nonvascularized iliac
      crest bone graft.
AB  - Scaphoid nonunions present a challenging clinical problem, particularly if the
      diagnosis of nonunion is missed or delayed. The optimal management technique can
      vary from free vascularized bone grafts to scaphoid excision and limited wrist
      fusion. The classic method of open reduction, nonvascularized corticocancellous
      bone grafting and internal fixation is still an effective technique. In this
      report, we describe a case of a 28-year-old chronic scaphoid nonunion treated
      with nonvascular iliac crest bone graft and internal fixation. 

PMID- 24436794
TI  - Subluxation of the Palmar Radioulnar Ligament As a Cause of Blocked Forearm
      Supination: A Case of DRUJ Locking.
AB  - We report a case of locking of the distal radioulnar joint (DRUJ) due to
      interposition of a flap of the palmar radioulnar ligament (RUL) torn from the
      triangular fibrocartilage complex (TFCC). We released the blockage by elevating
      the flap and partially resecting a portion of the triangular fibrocartilage (TFC)
      arthroscopically. 

PMID- 24436795
TI  - Distal ulna hook plate: angular stable implant for fixation of distal ulna.
AB  - Distal ulna fractures, especially styloid injuries, classically have not been
      repaired, and only recently have these injuries been considered important.
      Certain fracture patterns of the distal ulna contribute to distal radioulnar
      joint (DRUJ) incongruity and potential instability. Appropriate fixation of the
      distal ulna is frequently difficult for several reasons: (1) high incidence of
      osteoporois in the affected patient population, (2) proximity of the injury to
      articular surfaces, and (3) lack of a proper implant to treat these injuries. The
      2.0-mm locking compression distal ulna plate (LC-DUP) is an anatomically
      contoured implant with a low profile and fixed angle that provides proper
      stability to treat injuries of the distal ulna. The plate was designed for the
      treatment of distal ulna fractures, but its success has led to an extension of
      its indications to be used in treating symptomatic basistyloid ulnar nonunions
      and in ulnar shortening osteotomy for ulnocarpal abutment syndrome. The authors'
      description of the techniques used for each indication as well as their
      perspectives in the treatment of distal ulna injuries are described in detail in
      this report. 

PMID- 24436797
TI  - Acute Distal Radius Fracture: PAF Analysis.

PMID- 24436796
TI  - The distal oblique bundle of the distal interosseous membrane of the forearm.

PMID- 24436799
TI  - From scapholunate interosseus ligament to scapholunate ligament complex.

PMID- 24436798
TI  - The Scapholunate Ligament Complex (SLLC).

PMID- 24436800
TI  - How I see the wrist.

PMID- 24436801
TI  - The EWAS Classification of Scapholunate Tears: An Anatomical Arthroscopic Study.
AB  - Treatment of scapho-lunate (SL) injuries is still a challenge for the surgeon,
      especially in chronic cases. The aim of the study isto experimentally cut,
      specific portions of scapholunate ligament and extrinsic ligaments and check
      their corresponding arthroscopic finding in order to understand the pathogenesis
      and develop a new classification system which is an evolution of the present
      arthroscopic classifications. Materials and Methods Thirteen cadaver wrists were
      studied under arthroscopy. Different portions of the scapho-lunate ligament were
      subsequently sectioned. In group A the sectioning sequence was: anterior SLIOL,
      RSC, LRL, SLIOL's proximal and posterior, DIC, DRC ligament and ST ligaments (8
      cases). In group B it was: SLIOL's posterior and proximal, DIC, SLIOL's anterior,
      LRL, RSCL, DRC, ST ligaments (5 cases). The anatomo-pathological findings after
      each sectioning were correlated to the classification system proposed (Table 1).
      Results In group A, stage 3A was obtained when SL ligament's volar and
      intermediate portion and/ or SC/LRL ligaments were sectioned. A stage 3C was
      obtained when section of posterior SLIOL was sectioned as well. A stage IV when
      the DIC was also sectioned. In group B a stage 3B was obtained by cutting
      intermediate, posterior portion of the SLIOL ligament and DIC. A stage 3C was
      obtained when the anterior part of the SLIOL was also sectioned. In all cases,
      sectioning of the SLIOL lead to a stage 3C only if associated with sectioning of
      at least one of the extrinsic stabilizers (DIC or SC/LRL). Sectioning of DIC and
      SC ligament, in addition to SLIOL led to an arthroscopic stage IV. When ST, DRC
      and TH ligaments were also sectioned significant radiological signs appeared
      (stage V). Conclusions This study helps us to understand the anatomo-pathological
      scapho-lunate lesions in their different stages of partial lesions. Commonly
      called scapho-lunate lesions are complex, involving also extrinsic ligaments. 

PMID- 24436802
TI  - Scapholunate ligament reconstruction.
AB  - Background Scapholunate reconstruction poses a challenge to orthopedic surgeons.
      Materials and Methods Prospective cohort. Description of Technique Our technique
      for scapholunate (SL) reconstruction involves ligament reconstruction utilizing a
      portion of the flexor carpi radialis tendon rerouted via transosseous tunnels
      across the scaphoid, lunate, and triquetrum (scapholunotriquetral tenodesis). The
      tendon graft is secured with interference screw fixation into the triquetrum. The
      philosophy of this new technique is to reduce subluxation and maintain the
      relationship between scaphoid and lunate by placing a graft through the center of
      the SL articulation. This graft is then tensioned by passing it centrally through
      the lunate and triquetrum and secured using an interference screw in the
      triquetrum. Secondary stabilizers, including the dorsal intercarpal ligament, are
      then augmented by passing the graft back to the scaphoid, crossing from the
      triquetrum over the proximal capitate. This further reinforces the translational
      relationship between the scaphoid and the triquetrum and, therefore, augments
      stability of the SL articulation. Results We have utilized this technique
      successfully in over 40 patients since 2009. We report on a prospective
      consecutive series of 11 patients with over 12 months follow-up (range 12 to 24
      months) demonstrating good early radiological and clinical outcomes. Conclusions
      In developing this technique, we aimed to take the best features of previously
      described techniques and address the perceived shortcomings of each. We believe
      there are several benefits of our technique. Moreover, few other techniques
      address as many of the aspects of chronic SL instability as our technique does. 

PMID- 24436803
TI  - Current role of open reconstruction of the scapholunate ligament.
AB  - This paper is a review of the various surgical techniques used in repair or
      reconstruction of the scapholunate ligament according to the clinical stages and
      anatomic-pathologic findings. Arthroscopy permits a direct evaluation of the
      scapholunate injury and the status of the articular surfaces. Specific
      indications for each type of scapholunate ligament tear are proposed, from the
      different types of dorsal capsulodesis to bone-ligament-bone techniques and
      tenodesis procedures. The authors' preferred techniques and literature review of
      the expected outcomes are presented. 

PMID- 24436804
TI  - Arthroscopic volar capsuloligamentous repair.
AB  - Background The palmar aspect of the capsuloligamentous complex of the wrist is
      relatively inaccessible to surgery through an open approach. An all-inside
      arthroscopic suturing technique is presented that allows suturing of the palmar
      scapholunate or lunotriquetral ligaments or plication of the space of Poirier.
      Methods Eight palmar scapholunate ligaments and four major tears of the volar
      capsuloligamentous complex of the wrist due to a perilunate dislocation have been
      repaired. Results No complications occurred during or after the procedure. It was
      not possible to separate the effects of the palmar repair from the disparate
      treatment of the associated pathology. Conclusions The technique described allows
      one to suture the palmar aspects of the SL and LT ligaments safely and to repair
      the space of Poirier structures without need for any special equipment. 

PMID- 24436805
TI  - Arthroscopic management of scapholunate instability.
AB  - Wrist arthroscopy plays a valuable role in the management of scapholunate
      instability. A spectrum of injuries can occur to the scapholunate interosseous
      ligament, which may be difficult to detect with imaging studies. Wrist
      arthroscopy enables detection and management of injury to the scapholunate
      ligament under bright light and magnified conditions, in both acute and chronic
      situations. 

PMID- 24436806
TI  - Scapholunate instability: proprioception and neuromuscular control.
AB  - From a kinetic point of view, the wrist is considered stable when it is capable
      of resisting load without suffering injury. Several prerequisites are necessary
      for the wrist to be kinetically stable: bone morphology, normal articulating
      surfaces, ligaments, the sensorimotor system, the muscles crossing the wrist, and
      all nerves connecting to ligaments and muscles. Failure of any one of these
      factors may result in carpal instability. The terms "scapholunate (SL)
      dissociation" and "SL instability" refer to one of the most frequent types of
      wrist instability, resulting from rupture or attenuation of the SL supporting
      ligaments. From a radiologic point of view, SL instability may be dynamic or
      static. Unlike static instabilities, which tend to be painful and dysfunctional,
      a good proportion of dynamic SL instabilities remain asymptomatic and stable for
      prolonged periods of time. Such a lack of symptoms suggests that a ligament
      rupture, in itself, is not enough for a joint to become unstable. Certainly, the
      process of achieving stability is multifactorial and involves normal joint
      surfaces, ligaments, muscles, and a complex network of neural connections linking
      all these elements. In this article, we will review the neuromuscular
      stabilization of the SL joint and the proprioceptive mechanisms that contribute
      to the dynamic carpal stabilization. 

PMID- 24436807
TI  - Arthroscopic dorsal capsulo-ligamentous repair in the treatment of chronic scapho
      lunate ligament tears.
AB  - Introduction Scapholunate ligament injuries usually result due to a fall on the
      outstretched hand leading to scapholunate instability. The natural history of
      untreated scapholunate instability remains controversial and usually results in
      late arthritic changes- the so-called "SLAC" wrist. The advent of wrist
      arthroscopy helps in early diagnosis and treatment of these serious injuries. In
      selected cases with reducible scapholunate instability (Garcia-Elias stages 2, 3
      and 4) we propose a new "all arthroscopic dorsal capsulo- ligamentous repair"
      with the added advantage of early rehabilitation and prevention of post-operative
      stiffness. Material and Methods We report the results of our series of 57
      consecutive patients suffering from chronic wrist pain refractory to conservative
      measures. All patients underwent a thorough clinical examination in addition to a
      standard set of radiographs and MRI exam; and they were treated by an all
      arthroscopic dorsal capsulo-ligamentous repair under loco-regional anesthesia on
      an ambulatory basis. All patients were available for follow-up at regular
      intervals during the post-operative period. At follow-up, the wrist ROM in all
      directions, the grip strength, DASH questionnaire and pain relief based on the
      VAS were recorded for both- the operated and contra-lateral sides. Results There
      were 34 males & 23 females with a mean age of 38.72 +/- 11.33 years (range 17-63
      years). The dominant side was involved in 52 cases. The mean time since injury
      was 9.42 +/- 6.33 months (range 3-24 months) and the mean follow-up was 30.74 +/-
      7.05 months (range 18-43 months). The mean range of motion improved in all
      directions. The mean difference between the post- and pre-operative extension was
      14.03 degrees  (SEM = 1.27 degrees ; p < 0.001); while the mean difference
      between the post-and pre-operative flexion was 11.14 degrees  (SEM = 1.3 degrees
      ; p < 0.0001) with flexion and radial deviation reaching 84.3% and 95.72%
      respectively of the unaffected wrist. The mean difference for the VAS score was 
      5.46 (SEM = 0.19; p < 0.0001). The mean post-operative grip strength of the
      affected side was 38.42 +/- 10.27 kg (range 20-60 kg) as compared with mean pre
      operative grip strength of 24.07 +/- 10.51 kg (range 8-40 kg) (p < 0.0001). The
      mean post-operative grip strength of the operated side was 93.4% of the
      unaffected side. The DISI was corrected in all cases on post-operative
      radiographs. The mean difference between the post-and pre-operative SL angles was
      -8.95 degrees  (SEM = 1.28 degrees ; p < 0.0001). The mean post-operative DASH
      score was 8.3 +/- 7.82 as compared with mean pre-operative DASH score of 46.04 +/
      16.57 (p < 0.0001). There was a negative co-relation between the overall DASH
      score and the post-operative correction of the DISI deformity with a lower DASH
      score associated with increasing SL angles. Discussion The dorsal portion of the
      scapholunate ligament is critical for the stability scapholunate articulation,
      largely due to its attachment to the dorsal capsule. We have recently conducted a
      multi-centric anatomical study with international collaboration demonstrating the
      critical importance of this dorsal scapholunate complex. The all arthroscopic
      capsulo-ligamentous repair technique provides reliable results in addition to
      avoiding postoperative stiffness. The overall results at a mean follow-up period
      of more than 2 years in our series of young, active patients appear to be
      encouraging. 

PMID- 24436808
TI  - Anatomical Description of the Dorsal Capsulo-Scapholunate Septum (DCSS)
      Arthroscopic Staging of Scapholunate Instability after DCSS Sectioning.
AB  - Background The dorsal capsuloligamentous scapholunate septum (DCSS) is a
      confluence of the dorsal capsule, the dorsal intercarpal ligament (DIC), and the
      scapholunate interosseous ligament (SLIOL). It appears to play a role in the
      stability of the scapholunate articulation. The purpose of this study was to
      describe the anatomical basis for this structure and to investigate its role in
      scapholunate instability through sectioning of this structure followed by an
      arthroscopic and fluoroscopic analysis. Material and Methods In the anatomical
      part of the study we dissected 3 fresh cadaver wrists to examine the anatomy of
      the DCSS. In the arthroscopic part of the study we assessed the EWAS grade of SL
      instability before and after sectioning the DCSS and measured the scapholunate
      and radiolunate angles fluoroscopically. Results Sectioning the DCSS increased
      the EWAS grade of SL instability but did not affect the scapholunate gap, the
      scapholunate angle or radiolunate angle. Conclusion We have demonstrated that
      there is a distinct structure that is separate from the dorsal capsule, which we
      have labeled the Dorsal Capsuloligamentous Scapholunate Septum. We believe that
      the DCSS is a previously unreported secondary stabilizer of the SL joint which
      may have therapeutic and prognostic implications. 

PMID- 24436809
TI  - Radiographic evaluation of chronic static scapholunate dissociation post soft
      tissue reconstruction.
AB  - The purpose of this study was to examine the radiographic outcomes of dorsal
      intercarpal ligament capsulodesis (DILC), documenting the time to carpal collapse
      postoperatively. From January 2008 to January 2011, 12 patients were identified
      with chronic scapholunate (SL) dissociation. The average follow-up period was
      15.8 months. Paired t-tests were used preoperatively, one month after pin
      removal, and at final follow-up to determine significance in radiographic
      outcomes. The Disabilities of the Arm, Shoulder, and Hand (DASH) survey was
      administered to patients before and after surgery to assess subjective levels of
      pain, function, and satisfaction. Intraoperatively all deformities were reduced
      completely. One month after pin removal, the mean SL gap was 3.3 mm, the SL angle
      was 74 degrees , the radiolunate (RL) angle was 17 degrees , and the
      lunatocapitate (LC) angle was 8 degrees . Only the SL angle improved; the other
      measurements remained unchanged. At final follow-up, the mean SL gap was 3.6 mm,
      the SL angle was 78 degrees , the RL angle was 20 degrees , and the LC angle was
      10 degrees . SL angle worsened, but with no statistically significant difference.
      The other radiographic measurements remained unchanged at final follow up. Wrist
      flexion and extension decreased from 76% and 69% of the contralateral side to 62%
      and 56% of the contralateral side after surgery. Grip strength was 64% of the
      contralateral side before surgery and 83% after surgery. Visual Analog Scale
      (VAS) results improved from 6.3 to 1.7, and DASH scores improved from 39 to 8
      after the surgery. DILC cannot withstand large and repetitive forces. Carpal
      collapse recurred within a short time after DILC. However, our small patient
      numbers and short term follow-up preclude any conclusions with respect to
      clinical efficacy of this procedure. Limitations of this study include the fact
      that this is a retrospective study with no control group. In addition, it
      represents a single-surgeon series, which introduces a source of bias and carries
      the risk of technical and methodological flaws, which may have contributed to the
      observed radiographic outcomes. 

PMID- 24436810
TI  - Dorsal wrist capsular tears in association with scapholunate instability: results
      of an arthroscopic dorsal capsuloplasty.
AB  - Purpose The purpose of this study is to report the association of dorsal wrist
      capsular avulsion with scapholunate ligament instability and to evaluate the
      results of an arthroscopy-assisted repair. Methods We retrospectively reviewed 10
      patients with a mean age of 39.1 years suffering from chronic dorsal wrist pain.
      They underwent a wrist arthroscopy with an evaluation of the scapholunate
      ligament complex from the radiocarpal and midcarpal compartments. An avulsion of
      the dorsal intercarpal ligament (DICL) from the scapholunate interosseous
      ligament (SLIL) was visible from the radiocarpal compartment in all cases, while
      the SLIL was intact. The DICL tear was repaired with an arthroscopy-assisted
      dorsal capsuloplasty. Patients were assessed preoperatively and postoperatively
      by the QuickDASH (Disabilities of the Arm, Shoulder, and Hand) questionnaire, by
      the Visual Analog Scale (VAS) for pain, and by a clinical and radiological
      examination. Results Preoperatively, all patients had reduced flexion and radial
      deviation of the affected wrist. On the lateral radiograph, 5 of the 10 patients
      showed an increase of the scapholunate angle (60 to 85 degrees ). The
      scapholunate instability was graded as Messina-European Wrist Arthroscopy Society
      (EWAS) II in five cases and as grade IIIB in five cases. A tear of the ulnar part
      of the triangular fibrocartilage complex (TFCC) was found in seven cases. At a
      mean followup of 16 months, the wrist range of motion (ROM), the grip strength,
      the QuickDASH, and the VAS of pain improved significatively. The scapholunate
      angle was normalized in all cases. Discussion Isolated tears of the DICL at its
      insertion from the dorsal part of the SLIL can be associated with scapholunate
      instability in the absence of an injury to the SLIL. The diagnosis is made
      arthroscopically. The arthroscopic dorsal capsuloplasty is a minimally invasive
      technique that provides short-term satisfactory results. Further studies are
      needed to determine whether repair of the DICL tear could prevent secondary
      destabilization of the scapholunate ligament complex. Level of evidence IV (case
      series) Diagnosis. 

PMID- 24436811
TI  - Dorsal capsuloplasty for dorsal instability of the distal ulna.
AB  - Background Dorsal instability of the distal ulna can lead to chronic wrist pain
      and loss of function. Structural changes to the dorsal radioulnar ligaments
      (DRUL) of the triangular fibrocartilage complex (TFCC) and the dorsal capsule
      around the ulnar head with or without foveal detachment can lead to volar
      subluxation of the distal radius e.g., dorsal instability of the distal ulna.
      Purpose Is to evaluate the post-operative results of reinstituting distal
      radioulnar joint (DRUJ) stability through reefing of the dorsal capsule and
      dorsal radioulnar ligaments, with and without a foveal reattachment of the TFCC.
      Methods A total of 37 patients were included in this retrospective study.
      Diagnosis and treatment was based strictly on dry wrist arthroscopy. In 17
      patients isolated reefing of the DRUL and their collateral tissue extension was
      performed. In 20 patients an additional foveal reinsertion was performed.
      Postoperative results were evaluated with the DASH questionnaire, VAS scores,
      grip strength and range of motion. These findings were extrapolated in the Mayo
      wrist score. The two subgroups were compared. Results Mayo wrist scores of the
      whole population had a mean of 73. There was no difference between the group that
      was treated with reefing of the DRUL only and the group that was treated with a
      combined foveal reinsertion. Conclusion This relatively simple 'dorsal reefing'
      procedure, with foveal reinsertion when indicated, is a reliable method to
      restore volar-dorsal DRUJ stability with a significant decrease in pain
      sensation, good DASH scores and restoration of functional grip strength and ROM.
      Type of Study/Level of Evidence Therapeutic, Level IV. 

PMID- 24436812
TI  - A minimal wrist arthroplasty for early wrist osteoarthritis.
AB  - Background The most common forms of salvage surgery for wrist arthritis of any
      stage are four corner fusion and proximal row carpectomy. Younger, high demand
      patients with early arthritis may not be candidates for this type of salvage
      surgery. We describe a technique and preliminary case series of a minimal
      radiocarpal arthroplasty aimed at patients with initial and isolated wrist
      arthritis (stage 1). This procedure does not preclude any procedure that may
      become necessary in the future. Patients A series of nineteen male heavy laborers
      with scapholunate advanced collapse (SLAC grade 1-2) wrist osteoarthritis that
      felt the wrist arthritis was prohibiting their function enough to warrant
      surgery, but were unwilling to undergo a salvage procedure, were treated with the
      technique. The average age was 57.2 (+/- 7.7) years. The average follow up period
      was 40.3 months (9-63 months). All patients returned to heavy labor. No revision
      surgery was needed within the follow up period. Range of motion (ROM) and grip
      strength did not significantly improve. Patient satisfaction was high despite
      imperfect results. Conclusions Minimal arthroplasty as described may provide a
      temporary solution for active patients with symptomatic early wrist arthritis who
      are not candidates for salvage wrist surgery. Longer -term follow up as well as
      investigation of additional stabilization procedures is necessary. 

PMID- 24436813
TI  - Causes of a block to forearm rotation after distal radius fractures.
AB  - Three cases of a block to forearm rotation after a distal radius fracture were
      presented. The unique feature is that the surgeon should be diligent in seeking
      and rectifying causes of distal radioulnar joint (DRUJ) instability and rotation
      loss after fracture treatment. 

PMID- 24436814
TI  - Anatomy and clinical relevance of the ulnocarpal ligament.

PMID- 24436816
TI  - Editorial.

PMID- 24436815
TI  - Management distal radius and distal ulnar fractures with fragment specific plate.
AB  - This article describes the use of a new generation low profile dorsal rim plate
      for management of distal radius fractures from the dorsal approach. This plate
      was designed to maximize stability while minimizing complications from the
      extensor tendons. A volar ulnar plate designed to specifically stabilize
      fractures of the ulnar head and neck is also described. 

PMID- 24436817
TI  - The wrist in my three lifetimes.

PMID- 24436818
TI  - Technique: Osteochondral Grafting of Capitate Chondrosis in PRC.
AB  - Background Proximal row carpectomy (PRC) is a useful treatment option for wrist
      arthritis, but the operation is contraindicated when there is arthritis of the
      capitate head. We describe a technique that involves resurfacing of a capitate
      that has focal chondrosis, using an osteochondral graft harvested from the
      resected carpal bones. Materials and Methods PRC patients who had a focal area of
      capitate chondrosis underwent osteochondral grafting of the capitate. Pre- and
      postoperative pain level, employment status, motion, grip strength, and Modified
      Mayo Wrist Scores (MMWS) were assessed. Postoperative Disability of the Arm,
      Shoulder, and Hand (DASH) scores were also calculated. Description of Technique
      The articular surface of the capitate is assessed for need for grafting. The
      proximal row is resected with the lunate removed intact. The arthritic area is
      prepared. The graft is taken from the lunate and placed in the prepared site of
      the capitate. Results Eight patients (average age of 53 years) were followed for
      18 months. Pain: Preoperatively, moderate to severe in 7 patients;
      postoperatively, mild to no pain in 7 patients. Motion: Preoperative, 84 degrees 
      (74% of the contralateral side); postoperative 75 degrees  (66%). Grip Strength:
      Preoperative, 29 kg (62%); postoperative, 34 kg (71%). Mayo Wrist Score:
      Preoperative, 51 (poor); postoperative, 68 (fair). Average postoperative DASH
      score was 19.5. Follow-up radiographs showed that 75% of patients had mild to no
      degeneration. Conclusions Osteochondral grafting in PRC offers satisfactory
      results in terms of pain relief, return to work, motion, and grip strength. Level
      of Evidence Therapeutic IV, Case series. 

PMID- 24436819
TI  - Arthroscopic osteochondral grafting for radiocarpal joint defects.
AB  - Background Focal chondral lesion is a common cause of chronic wrist pain. The
      best treatment remains unknown. We have developed a technique of arthroscopic
      transplantation of an osteochondral autograft from the knee joint to the distal
      radius with satisfactory clinical results. Materials and Methods Between December
      2006 and December 2010, four patients (average age 31 years) with posttraumatic
      osteochondral lesions over the dorsal lunate fossa were treated with arthroscopic
      osteochondral grafting. Pre- and postoperative motion, grip strength, wrist
      functional performance score, pain score, and return to work status were charted.
      Postoperative computed tomography (CT) scan, magnetic resonance imaging (MRI),
      and second-look arthroscopy were performed to assess graft incorporation.
      Description of Technique With the arthroscope in the 3-4 portal, synovitis over
      the dorsal lunate fossa was debrided to uncover the underlying osteochondral
      lesion. We employed the 6-mm trephine of the Osteoarticular Transfer System
      (OATS) to remove the osteochondral defect. Osteochondral graft was harvested from
      the lateral femoral condyle and delivered into the wrist joint arthroscopically.
      Results In all cases, grafts incorporation was completed by 3-4 months
      postoperative. All patients showed improvement in the wrist performance score
      (preoperative 27.5, postoperative 39 out of 40) with no pain on final follow-up
      at average 48.5 months (range 24-68 months). Grip strength improved from 62.6 to
      98.2% of the contralateral side. Motion improved from 115.5 to 131.3 degrees . X
      ray images showed preserved joint space. Patient satisfaction was high with no
      complication. Conclusion An arthroscopic-assisted transfer of an osteochondral
      graft is a viable treatment option for chondral defects of the distal radius. 

PMID- 24436820
TI  - Thumb carpometacarpal arthroplasty with ligament reconstruction and interposition
      costochondral arthroplasty.
AB  - Background Thumb arthritis at the carpometacarpal (CMC) joint is one of the most
      common sites of arthritis, especially in women. Thumb arthroplasty is an
      effective method of relieving pain and improving function. Materials and Methods
      Qualitative and quantitative outcomes were assessed clinically and
      radiographically in 58 patients (66 thumbs) with thumb basal joint arthritis
      limited to the trapeziometacarpal joint, treated with hemiresection arthroplasty
      of the trapezium, flexor carpi radialis (FCR) ligament reconstruction, and
      allograft costochondral interposition graft. Description of Technique The thumb
      CMC joint arthroplasty is performed using an FCR tendon for ligament
      reconstruction combined with removal of the distal half of the trapezium, which
      is replaced with a life preserver-shaped spacer that is carved out of allograft
      cartilage. Results Results of the validated Disability of Arm, Shoulder, and Hand
      (DASH) questionnaire at a mean follow-up time of 56 months (range, 24-103 months)
      revealed that 90% of the patients had a high level of function with minimal
      symptoms. Important improvements in web space with increased palmar and radial
      abduction and grip and pinch strength measurements were observed. The
      trapeziometacarpal space had decreased 21% after surgery, while
      trapeziometacarpal subluxation was 14% compared with 21% before surgery. There
      was an inverse correlation between the loss of trapezial height and subluxation
      and clinical outcome. Conclusions The results of this study demonstrate that,
      although the preoperative trapezial height was not maintained, the reconstructed
      thumbs remained stable, with little subluxation and improved clinical outcomes.
      Level of Evidence IV, retrospective case series. 

PMID- 24436821
TI  - Proximal scaphoid arthroplasty using the medial femoral trochlea flap.
AB  - Background The medial trochlea of the femur (medial femoral trochlea, MFT)
      provides a source of convex osteocartilaginous vascularized bone that has been
      demonstrated to have a similar contour to the proximal scaphoid. This provides a
      potential solution for difficult recalcitrant proximal pole scaphoid nonunions.
      Materials and Methods Sixteen consecutive patients who underwent MFT proximal
      scaphoid arthroplasty were reviewed. Follow-up data were recorded at a minimum of
      6 months, with an average of 14 months. The results of this cohort were
      previously reported in detail but are summarized herein. Description of Technique
      The ability to reconstruct both bone and cartilage of the nonunion enables the
      surgeon to resect the nonunited proximal pole to prepare for scaphoid
      reconstruction. A segment of osteocartilaginous MFT is harvested in dimensions
      required by the scaphoid defect. The MFT segment is harvested on the transverse
      branch of the descending geniculate vessels. Fixation may be achieved with ease
      due to the size of the reconstructed segment. Results Computed tomography imaging
      demonstrated 15 of 16 reconstructed scaphoids achieving osseous union. Follow-up
      range of motion (ROM) of the wrist averaged 46.0 degrees  extension (range 28-80
      degrees ) and 43.8 degrees  flexion (range 10-80 degrees ), which was similar to
      preoperative (average 45.7 degrees  extension and 43.0 degrees  flexion).
      Scapholunate angles remained unaffected (51.6 degrees  preoperatively and 48.6
      degrees  postoperatively), indicating preservation of carpal relationships.
      Conclusions Vascularized MFT flaps provide a useful tool in the treatment of
      difficult proximal pole scaphoid nonunions. Early follow-up demonstrates high
      rate of achieving union with acceptable ROM and good pain relief. 

PMID- 24436822
TI  - Rib cartilage graft for posttraumatic or degenerative arthritis at wrist level:
      10-year results.
AB  - Background Posttraumatic arthritides of the radiocarpal joint, secondary to
      scaphoid nonunion advanced collapse (SNAC), scapholunate advanced collapse
      (SLAC), or Kienbock disease or in cases of intraarticularmalunion of the distal
      radius, are classically solved by some type of arthrodesis procedure.
      Osteochondral grafting provides a possible motion-sparing option that can
      diminish pain in the active patient. Description of Technique A chondrocostal
      graft harvested from the ninth rib was inserted and fixed with a plate in place
      of the articular defect in cases of a malunited intra-articular distal radius
      fracture (7 cases) or to replace the proximal pole of the scaphoid in cases of
      SNAC or SLAC (18 cases). In Kienbock disease, the graft was inserted as a free
      cartilage spacer (4 cases). Results Harvesting the graft from the ninth rib had
      minimal morbidity without pleural injury in the reported series. Graft union was
      achieved in all cases of fixation. No graft resorption or necrosis were observed
      on X-ray and magnetic resonance imaging (MRI) evaluation at the longest follow-up
      of 10 years. Histological analysis performed at the time of plate removal showed
      the vitality of the graft. Two thirds of the patients had excellent or good
      results using the Green and O'Brien score. Conclusions Reconstruction of a
      partially destroyed articular surface using a costal graft is reliable and
      provides an alternative option for resurfacing the articular surface with viable
      cartilage. 

PMID- 24436823
TI  - Trends in wrist arthroscopy.
AB  - Background Wrist arthroscopy plays a role in both the diagnosis and the treatment
      of wrist pathology. It has evolved in the last three decades. Questions The
      present status of wrist arthroscopy was investigated by answering the following
      questions: -What is its current position in the treatment wrist pathologies
      according to the literature? -What is its current position according to hand
      surgeons? Methods Analysis of the number of publications on wrist arthroscopy was
      performed and compared with the number of publications on other arthroscopy
      topics to assess the current position of wrist arthroscopy. The members of the
      EWAS (European Wrist Arthroscopy Society) and the members of eight national hand
      surgery societies were questioned on wrist arthroscopy in daily practice. Results
      From 1975 till now, 925 papers on wrist arthroscopy were found. The publications
      on wrist arthroscopy increased from an average of 8/year (1986) to 26/year
      (2012). More than half (56.9%) of the respondents of the EWAS perform fewer than
      5 wrist arthroscopies per month, and only 7 (10.8%) indicate the performance of
      more than 10 wrist arthroscopies per month. Seventy-four percent of the
      orthopedic hand surgeons perform wrist arthroscopy (in 48.5% for therapeutic
      indications) against 36.8% of plastic surgery hand surgeons (in 23.1% for
      therapeutic indications). Conclusion Wrist arthroscopy has taken up a place in
      the armamentarium of the hand surgeon. The place of wrist arthroscopy in daily
      practice is related to the background of the hand surgeon. 

PMID- 24436824
TI  - Volar plate fixation of intra-articular distal radius fractures: a retrospective
      study.
AB  - Background Intra-articular fractures of the distal radius represent a therapeutic
      challenge as compared with the unstable extra-articular fractures. With the
      recent development of specifically designed internal fixation materials for the
      distal radius, treatment of these fractures by fragment-specific implants using
      two or more incisions has been advocated. Purpose The purpose of this study was
      to investigate the efficacy of a fixed-angle locking plate applied through a
      single volar approach in maintaining the radiographic alignment of unstable intra
      articular fractures as well as to report the clinical outcomes. We only excluded
      those with massive comminution, as is discussed in greater detail in the text.
      Patients and Methods This is a multicentered, retrospective study involving three
      hospitals situated in Spain, Switzerland, and the United States. In the period
      between January 2000 and March 2006, 97 patients with 101 intra-articular distal
      radius fractures, including 13 volarly displaced and 88 dorsally angulated
      fractures were analyzed. Over 80% were C2/C3 fractures, based on the AO
      classification. 16 open fractures were noted. Results With an average follow-up
      of 28 months (range 24-70 months), the range of movement of the wrist was very
      satisfactory, and the mean grip strength was 81% of the opposite wrist. The
      Disabilities of the Arm, Shoulder, and Hand (DASH) score was 8. The complications
      rate was < 5%, including loss of reduction in two patients. All fractures healed
      by 3 months postinjury. Conclusions Irrespective of the direction and amount of
      initial displacement, a great majority of intra-articular fractures of the distal
      radius can be managed with a fixed-angle volar plate through a single volar
      approach. Level IV retrospective case series. 

PMID- 24436825
TI  - Ligament origins are preserved in distal radial intraarticular two-part
      fractures: a computed tomography-based study.
AB  - Background Operative fixation of intraarticular distal radius fractures is
      increasingly common. A greater understanding of fracture patterns will aid
      surgical fixation strategy. Previous studies have suggested that ligamentous
      insertions may less commonly be involved, but these have included heterogeneous
      groups of fractures and have not addressed Lister's tubercle. Purpose We
      hypothesize that fracture lines of distal radial intraarticular 2-part fractures
      have reproducible patterns. They propagate through the cortical bone between
      ligament origins and do not involve Lister's tubercle. Methods Axial CT scans of
      two-part intraarticular distal radius fractures were assessed independently by
      two examiners. The fractures were mapped onto a grid and the cortical breaches
      expressed as a percentile of the total radial width or length. The cortical
      breaches were compared with the ligamentous insertions on the distal and Lister's
      tubercle. Associated injuries were also documented. Results The cortical breaches
      occurred between the ligamentous insertions in 85%. Lister's tubercle was not
      involved in 95% of the fractures. Three major fracture patterns emerged: radial
      styloid, dorsal, and volar. Each major pattern had two subtypes. Associated
      injuries were common. Scapholunate dissociation was associated with all types,
      not just the radial styloid fracture pattern. Conclusions The fracture patterns
      of two-part intraarticular fractures mostly involved the interligamentous zones.
      Three major groups were identified: dorsal, volar, and radial styloid. Lister's
      tubercle was preserved with fractures tending to propagate radial or ulnar to
      this structure. We suggest conceptualizing fracture fragments as osseo
      ligamentous units to aid prediction of fracture patterns and associated injury.
      Study Design Diagnostic III Level of Evidence 3. 

PMID- 24436826
TI  - Trapezial topography in thumb carpometacarpal arthritis.
AB  - Objective Contradictory reported arthritic patterns of the metacarpal surface of
      the trapezium include preferential volar wear, radial wear, and dorsal-ulnar
      sparing. We investigated whether a predominant wear pattern exists in surgical
      trapeziectomy for advanced thumb carpometacarpal (CMC) arthritis. Methods We
      examined 36 intact trapezia from 34 thumb CMC arthroplasty patients over an 18
      month period. The first metacarpal articular surface revealed three consistent
      morphology patterns: (1) saddle, (2) dish, and (3) cirque. The saddle represented
      cartilage loss with preservation of the normal trapezial morphology. The dish
      shape represented concave curvature, with loss of the normal saddle
      configuration. The cirque shape represented preferential volar concave wear,
      disrupting the convex volardorsal arc. Two surgeons classified the randomized
      specimens twice, blinded to patient identity and each other's categorization.
      Radiographic Eaton staging was correlated retrospectively for 35 of 36 of the
      trapezial specimens. Eight specimens were further quantified with micro-computed
      tomography (micro-CT). Results Thirty-six trapezia were classified as follows: 17
      (47%) saddle, 12 (33%) dish, and 7 (19%) cirque. Intra-rater reliability was 0.97
      and 0.95; inter-rater reliability in the second round was 0.95. The 36 trapezia
      represented 27 female (75%) and 9 male (25%) patients; 18 (50%) represented the
      dominant hand. Age at surgery averaged 64 (33-76). Complete cartilage loss of the
      entire metacarpal surface was seen in 15 (42%) of all specimens. Osteophyte
      presence was typically minimal in the saddle group; the dish group had
      characteristic extensive rimming osteophytes in a 91% female population (11/12),
      and the cirque group had volar osteophytes. Radiographic severity ranged from
      Eaton stage II to IV; less severe radiographic staging (Eaton II) predominated in
      the saddle configuration; advanced Eaton III-IV disease predominated in both
      cirque and dish shapes. Micro-CT verified the three discrete shapes with
      volardorsal and radioulnar orientation measurements. Conclusion The metacarpal
      surface of the trapezium demonstrates three distinct patterns of wear in
      arthritic surgical specimens. Sex, dominance, age distribution, and Eaton stage
      varied across the different shapes. Level of Evidence Level 3 Study Type
      Observational. 

PMID- 24436827
TI  - Malignant giant cell tumor in the carpal tunnel: a case report and review of
      literature.
AB  - Background Malignant tenosynovial giant cell tumors (GCTs) are extremely rare,
      and their etiology is unknown. However, this type of malignancy is associated
      with high metastasis and mortality rates. Therefore, the treatment of choice is
      wide excision. Case Description A 66-year-old man complained of tingling and loss
      of sensation in the left hand, caused by a tumor that compressed the median
      nerve. The tumor was excised. Histopathologic examination revealed a ganglion
      cyst. Two years later, the patient visited our clinic with recurrent and similar
      complaints of the left hand. This time, however, the lesion turned out to be a
      malignant tenosynovial GCT and was treated by amputation of the forearm.
      Literature Review Since 1979, only 37 malignant tenosynovial GCTs have been
      reported in literature. Follow-up of these patients showed that 11 patients died
      of the disease, 4 patients were still living with the disease, and 14 patients
      had no evidence of disease after treatment. The other seven patients were lost to
      follow-up, and one patient died of other causes. In these 37 patients, a high
      incidence of lymph node metastasis (41%) and a high mortality rate (30%) were
      seen. Clinical Relevance Although this malignant tenosynovial GCT is very rare,
      high mortality rates have been observed because of the high incidence of lymph
      node metastases. Therefore, more awareness has to be created, to recognize and
      treat this tumor timely. 

PMID- 24436829
TI  - The scapholunate ligament complex.

PMID- 24436828
TI  - Clinical Evaluation of the Articulinx Intercarpometacarpal Cushion for the First
      CMC Joint: A Feasibility Study.
AB  - Background The Intercarpometacarpal Cushion (ICMC; Articulinx, Cupertino, CA,
      USA) is an implantable spacer designed as a less invasive surgical treatment for
      osteoarthritis (OA) of the first carpometacarpal joint (CMC-1). Description of
      Technique Following local anesthesia and exposure of the joint capsule the ICMC,
      attached to a needle and suture tethers, is guided into the joint space under
      fluoroscopic visualization through a dorsal approach. The needle is pulled
      through the thenar eminence to the opposite side of the hand and, once proper
      device placement is confirmed, cut free and the joint capsule closed. Patients
      and Methods Eight female patients (median age 56 years; range, 42-83) were
      treated and followed for 6 to 24 months. Safety of the implant procedure was
      evaluated intraoperatively. Pain, joint function, and strength were evaluated at
      6 weeks, 3, 6, 12 and 24 months with a Visual Analog Scale (VAS) for pain, the
      QuickDASH inventory, Canadian Occupational Performance Measure (COPM), and pinch
      and grip strength measurements. Results At 2 years (n = 6), mean VAS pain scores
      decreased from 6.3 (+/- 1.5) to 2.2 (+/- 1.1) (p < 0.001), mean QuickDASH scores
      improved from 47 (+/- 15) to 31 (+/- 11) (p < 0.10), mean COPM performance scores
      improved from 5.0 (+/- 1.2) to 5.5 ( +/- 1.3) (p = NS). Mean pinch and grip
      strength measurements also improved compared with baseline. No serious adverse
      events occurred. Two device removals occurred, associated with a traumatic event
      and Stage IV OA with device displacement, at 6 and 9 months respectively.
      Conclusion The ICMC can be implanted safely. Effectiveness needs to be confirmed
      in future studies. 

PMID- 24436830
TI  - Statistical errors in clinical studies.

PMID- 24436831
TI  - An unlikely marriage: life as a wrist surgeon and career officer in the u.s.
      Navy.

PMID- 24436832
TI  - Augmented reality-based navigation system for wrist arthroscopy: feasibility.
AB  - PURPOSE: In video surgery, and more specifically in arthroscopy, one of the major
      problems is positioning the camera and instruments within the anatomic
      environment. The concept of computer-guided video surgery has already been used
      in ear, nose, and throat (ENT), gynecology, and even in hip arthroscopy. These
      systems, however, rely on optical or mechanical sensors, which turn out to be
      restricting and cumbersome. The aim of our study was to develop and evaluate the
      accuracy of a navigation system based on electromagnetic sensors in video
      surgery. METHODS: We used an electromagnetic localization device (Aurora,
      Northern Digital Inc., Ontario, Canada) to track the movements in space of both
      the camera and the instruments. We have developed a dedicated application in the
      Python language, using the VTK library for the graphic display and the OpenCV
      library for camera calibration. RESULTS: A prototype has been designed and
      evaluated for wrist arthroscopy. It allows display of the theoretical position of
      instruments onto the arthroscopic view with useful accuracy. DISCUSSION: The
      augmented reality view represents valuable assistance when surgeons want to
      position the arthroscope or locate their instruments. It makes the maneuver more
      intuitive, increases comfort, saves time, and enhances concentration.

PMID- 24436833
TI  - Computer-assisted percutaneous scaphoid fixation: concepts and evolution.
AB  - Background The treatment for undisplaced scaphoid waist fractures has evolved
      from conventional cast immobilization to percutaneous screw insertion.
      Percutaneous fixation reduces some of the risks of open surgery, but can be
      technically demanding and carries the risk of radiation exposure. Recently,
      computer-assisted percutaneous scaphoid fixation (CAPSF) has been gaining
      interest. Materials and Methods Conventional percutaneous scaphoid fixation is
      performed under fluoroscopic guidance and involves insertion of a guide wire
      along the length of the scaphoid to facilitate placement of a cannulated screw.
      Adapting computer-assisted techniques for scaphoid fixation poses several unique
      challenges including patient tracking and registration. Results To date, five
      groups have successfully implemented systems for CAPSF. These systems have
      implemented wrist immobilization strategies to resolve the issue of patient
      tracking and have developed unique guidance techniques incorporating 2D
      fluoroscope, cone-beam CT, and ultrasound, to circumvent patient-based
      registration. Conclusions Computer-aided percutaneous pinning of scaphoid waist
      fractures can significantly reduce radiation exposure and has the potential to
      improve the accuracy of this procedure. This article reviews the rationale for,
      and the evolution of, CAPSF and describes the key principles of computer-assisted
      technology. 

PMID- 24436834
TI  - Accuracy of 3D Virtual Planning of Corrective Osteotomies of the Distal Radius.
AB  - Corrective osteotomies of the distal radius for symptomatic malunion are time
      tested procedures that rely on accurate corrections. Patients with combined intra
      and extra-articular malunions present a challenging deformity. Virtual planning
      and patient-specific instruments (PSIs) to transfer the planning into the
      operating room have been used both to simplify the surgery and to make it more
      accurate. This report focuses on the clinically achieved accuracy in four
      patients treated between 2008 and 2012 with virtual planning and PSIs for a
      combined intra- and extraarticular malunion of the distal radius. The accuracy of
      the correction is quantified by comparing the virtual three-dimensional (3D)
      planning model with the postoperative 3D bone model. For the extraarticular
      malunion the 3D volar tilt, 3D radial inclination and 3D ulnar variance are
      measured. The volar tilt is undercorrected in all cases with an average of -6 +/-
      6 degrees . The average difference between the postoperative and planned 3D
      radial inclination was -1 +/- 5 degrees . The average difference between the
      postoperative and planned 3D ulnar variances is 0 +/- 1 mm. For the evaluation of
      the intraarticular malunion, both the arc method of measurement and distance map
      measurement are used. The average postoperative maximum gap is 2.1 +/- 0.9 mm.
      The average maximum postoperative step-off is 1.3 +/- 0.4 mm. The average
      distance between the postoperative and planned articular surfaces is 1.1 +/- 0.6
      mm as determined in the distance map measurement. There is a tendency to achieve
      higher accuracy as experience builds up, both on the surgeon's side and on the
      design engineering side. We believe this technology holds the potential to
      achieve consistent accuracy of very complex corrections. 

PMID- 24436835
TI  - Stem cells and biological approaches to treatment of wrist problems.
AB  - Stem cells are being intensively studied for their potential applications in
      clinical medicine. Mesenchymal stem cells (MSCs) are an important subset of stem
      cells which are attractive for application in musculoskeletal disorders. In this
      article, we review the characteristics of these MSCs that are relevant to
      clinical practice but that are still largely experimental in nature. 

PMID- 24436836
TI  - Objective outcomes following semi-constrained total distal radioulnar joint
      arthroplasty.
AB  - A dysfunctional distal radioulnar joint (DRUJ) can significantly compromise an
      individual's forearm rotation, grip, and weight bearing at the hand and wrist.
      This retrospective study reports surgeon- and therapist-collected objective wrist
      function and subjective pain scores of 10 patients who received the Scheker total
      DRUJ prosthesis. A review of these patients' medical records was performed to
      collect preoperative measurements of wrist range of motion (ROM), grip strength,
      and pain scores (0-10 scale). The degree of pronation, supination, flexion,
      extension, radial deviation, and ulnar deviation were the outcome measures used
      to evaluate wrist ROM. Postoperative measurements were collected at a follow up
      of 5 +/- 1.1 years in our clinic (minimum follow-up of 2yrs). Mean final wrist
      flexion and extension were 32.1 +/- 22.8 degrees  and 44.8 +/- 13.9 degrees ,
      respectively. Mean final supination and pronation were 72.5 +/- 14.4 degrees  and
      69.5 +/- 14.6 degrees , respectively. Average grip strength was 54.9 +/- 23.7
      lbs. The mean pain score was 3.6 +/- 3.1. Although there were no statistically
      significant changes in any of these outcome measures, the Scheker prosthesis
      improved wrist ROM (with the exception of wrist flexion) and decreased pain. Grip
      strength decreased by less than 1 lb but was still higher than the postoperative
      grip strength measurements in the literature for this prosthesis. Because of the
      self-stabilizing nature of this prosthesis and the satisfactory functional
      outcomes from this study and other studies, the Scheker prosthesis is still a
      viable option for DRUJ pathology that is refractory to nonimplant arthroplasties.
      This is a therapeutic level IV study. 

PMID- 24436837
TI  - Can total wrist arthroplasty be an option in the treatment of the severely
      destroyed posttraumatic wrist?
AB  - Background Severely destroyed posttraumatic wrists are usually treated by partial
      or total wrist fusion or proximal row carpectomy. The indications for and
      longevity of total wrist arthroplasty (TWA) are still unclear. Case Description
      The aim of this study was to analyze a series in which one last-generation total
      wrist arthroplasty was used as a salvage procedure for wrists with severe
      arthritis due to traumatic causes. The data were prospectively recorded in a web
      based registry. Seven centers participated. Thirty-five cases had a minimum
      follow-up time of 2 years. Average follow-up was 39 (24-96) months. Pain had
      improved significantly at follow-up, mobility remained unchanged. The total
      revision rate was 3.7%, and the implant survival was 92% at 4-8 years. Literature
      Review Very few studies have described specific results after TWA in
      posttraumatic cases and almost none using classical "third-generation" implants.
      The number of cases and the follow-up in the published series are small. Clinical
      Relevance Although painful posttraumatic wrists with severe joint destruction can
      be salvaged by partial or total fusion, we found that, evaluated at short- to
      midterm, total wrist arthroplasty can be an alternative procedure and gives
      results that are comparable to those obtained in rheumatoid cases. Level IV Case
      series. 

PMID- 24436838
TI  - Distal oblique bundle reconstruction and distal radioulnar joint instability.
AB  - Background This study created an anatomic reconstruction of the distal oblique
      bundle (DOB) of the interosseous membrane to determine its effect on distal
      radioulnar joint (DRUJ) instability and compare this technique with distal
      radioulnar ligament (DRUL) reconstruction. Questions/Purposes We hypothesized
      that this reconstruction would provide equivalent stability to DRUL
      reconstruction and that combining the two techniques would enhance stability.
      Methods Six cadaveric upper limbs were affixed to a custom frame. The
      volar/dorsal translation of the radius relative to the ulna was measured in 60
      degrees  pronation, neutral, and 60 degrees  supination. Translation was
      sequentially measured with the DRUJ intact, with sectioned DRULs and triangular
      fibrocartilaginous complex (TFCC), and with sectioned DOBs. Reconstructions were
      performed on the DRULs, on the DOB tensioned in both neutral and supination, and
      employing both techniques. Results The DOB reconstruction, tensioned both in the
      neutral position and in 60 degrees  supination, was more stable than the partial
      and complete instability in 6/6 specimens in pronation and the neutral position
      and in 5/6 specimens in supination. The DOB reconstruction and the DOB
      reconstruction tensioned in supination were more stable than the DRUL
      reconstruction in 4/6 patients. Combining the two techniques did not further
      reduce translation. Conclusions The DOB reconstruction is capable of improving
      stability in the unstable DRUJ. 

PMID- 24436839
TI  - Perilunate Injuries, Not Dislocated (PLIND).
AB  - Purpose We reviewed a series of equivalents of perilunate dislocations and
      fracture-dislocations (PLDs-PLFDs) in which there was no dislocation of the
      capitate from the lunate on the initial radiographs. We propose to include these
      injuries as a variant of perilunate dislocations that we have termed a perilunate
      injury, not dislocated (PLIND) lesion in a modified classification of perilunate
      injuries. Methods A review of the records of all acute perilunate injuries and
      displaced carpal fractures was done in a single-center university hospital wrist
      surgery unit over a 5-year period. All cases presenting at the acute stage with
      displaced fractures of scaphoid, lunate, triquetrum, or capitate along with
      scapholunate and/or lunotriquetral dissociation but no dislocation of the
      capitate from the lunate in the sagittal or coronal plane were reviewed and
      considered as PLIND lesions. Results We identified 11 patients with PLIND
      lesions. Three cases with clinical and radiological follow-up are presented.
      Discussion Equivalents of PLDs-PLFDs presenting without dislocation of the
      capitate from the lunate do exist. These injuries may be overlooked despite their
      severity. They require both osseous and ligamentous repair. Including them into
      an existing perilunate injuries classification highlights their recognition and
      enables a better understanding and treatment of both acute and chronic
      nondislocated perilunate injuries. Level of Evidence Level IV, retrospective case
      series. 

PMID- 24436840
TI  - Distal radius attachments of the radiocarpal ligaments: an anatomical study.
AB  - Background Understanding the anatomy of the ligaments of the distal radius aids
      in the surgical repair of ligamentous injuries and the prediction of
      intraarticular fracture patterns. Purposes (1) to measure the horizontal and
      vertical distances of the origins of the radiocarpal ligaments from the most
      ulnar corner of the sigmoid notch and the joint line, respectively; and (2) to
      express them as a percentile of the total width of the bony distal radius.
      Methods We dissected 8 cadaveric specimens and identified the dorsal radiocarpal,
      radioscaphocapitate, and the long and short radiolunate ligaments. Results The
      dorsal radiocarpal ligament attached from the 16th to the 52nd percentile of the
      radial width. The radioscaphocapitate ligament attached around the radial styloid
      from the 86th percentile volarly to the 87th percentile dorsally. The long
      radiolunate ligament attached from the 59th to the 85th percentile, and the short
      radiolunate ligament attached from the 14th to the 41st percentile. Discussion
      There was a positive correlation between the radial width and the horizontal
      distance of the ligaments from the sigmoid notch. These findings may aid
      individualized surgical repair or reconstruction adjusted to patient size and
      enable further standardized research on distal radial fractures and their
      relationship with radiocarpal ligaments. 

PMID- 24436841
TI  - Pyrocarbon interposition after capitate head resection.
AB  - Background Isolated lunocapitate disease is a rare situation. It includes both
      capitolunate arthritis and osteonecrosis of the capitate head. The management of
      this pathology is not defined yet. Case Description We treated three patients by
      resection of the capitate head and interposition of a so-called capitolunate
      Pi(2) implant (Tornier, BioProfile, Grenoble, France). We reported encouraging
      results at average follow-up of 4.8 years. Literature Review Several procedures
      have been reported in this indication. All suffer from lack of follow-up. Four
      corner fusion seems to be the most reliable solution at the expense of wrist
      stiffness. Clinical Relevance case series. 

PMID- 24436842
TI  - Arthroscopic resection of wrist ganglion arising from the lunotriquetral joint.
AB  - The dorsal wrist ganglion is the most common wrist mass, and previous studies
      have shown that it arises from the scapholunate interval in the vast majority of
      cases. Treatment has traditionally been open excision, and more recently
      arthroscopic resection has been established as an effective and less invasive
      treatment method. However, application of this technique to ganglia in atypical
      locations has not been reported, where open excision is the usual practice. This
      report describes two cases of atypical dorsal wrist ganglia that arose from the
      lunotriquetral (LT) joint, demonstrated by arthroscopic visualization and wrist
      arthrogram in one of them. Arthroscopic resection was performed, and the
      application of this technique to a dorsal wrist ganglion with an atypical origin
      and location is described. 

PMID- 24436843
TI  - A new distal radioulnar joint prosthesis.
AB  - Pain and instability of the distal radioulnar joint (DRUJ) are common sequelae
      following a fracture of the distal radius. Many soft tissue procedures have been
      described, not all of which are successful. Ulnar head replacement prostheses are
      available but do not always provide stability. We designed a two-part, easy to
      implant, distal radioulnar prosthesis and implanted it in 19 patients. The first
      prototype was inserted in 2002 and is still in place. During the study, the
      design was changed twice, resulting in three groups with four patients in group
      A, five in group B, and ten in group C. Unfortunately all five prostheses in
      group B had to be removed because of loosening, while only two prostheses in
      group C had to be removed, for nonprosthetic reasons. For the 12 patients who
      retained their prosthesis, forearm function increased while grip strength
      increased significantly. Pain scores decreased and the Disabilities of the Arm,
      Shoulder, and Hand (DASH) score improved but remained high. We conclude that the
      prosthesis offers a new treatment option for ulnar instability following distal
      ulnar resection. 

PMID- 24436844
TI  - Early Rehabilitation in the Intensive Care Unit: Preventing Physical and Mental
      Health Impairments.
AB  - Survivors of critical illness often experience new or worsening impairments in
      physical, cognitive and/or mental health, referred to as post-intensive care
      syndrome (PICS). Such impairments can be long-lasting and negatively impact
      survivors' quality of life. Early rehabilitation in the intensive care unit
      (ICU), while patients remain on life-support therapies, may reduce the
      complications associated with PICS. This article addresses evidence-based
      rehabilitation interventions to reduce the physical and mental health impairments
      associated with PICS. Implementation of effective early rehabilitation
      interventions targeting physical impairments requires consideration of 5 factors:
      barriers, benefits, feasibility, safety, and resources. Mental health impairments
      may be addressed by the following interventions: ICU diaries, early in-ICU
      psychological intervention, and post-ICU coping skills training. In both cases, a
      multidisciplinary team-based approach is paramount to the successful
      incorporation of early rehabilitation into routine practice in the ICU.

PMID- 24436845
TI  - Combined Transplantation of Human Neuronal and Mesenchymal Stem Cells following
      Spinal Cord Injury.
AB  - Transplantation of human fetal neural stem cells (hNSCs) previously demonstrated
      significant functional recovery after spinal cord contusion in rats. Other
      studies indicated that human mesenchymal stem cells (hMSCs) can home to areas of
      damage and cross the blood-brain barrier. The purpose of this article is to
      determine if combined administration of mesenchymal stem cells and neuronal stem
      cells improves functional outcomes in rats. The study design was a randomized
      controlled animal trial. Female adult Long-Evans hooded rats underwent
      laminectomy at T10 level. Moderate spinal cord contusion at T10 level was induced
      by the MASCIS Impactor. Four groups were identified. The MSC + NSC group received
      hMSCs intravenously (IV) immediately after spinal cord injury (acute) and
      returned 1 week later (subacute) for injection of hNSC directly at site of
      injury. The MSC-only group received hMSC IV acutely and cell media subacutely.
      The NSC-only group received cell media IV acutely and hNSC subacutely. The
      control group received cell media IV acutely and subacutely. Subjects were
      assessed for 6 weeks using Basso, Beattie, Bresnahan Locomotor Rating Score.
      Twenty-four subjects were utilized, six subjects in each group. Statistically
      significant functional improvement was seen in the MSC + NSC group and the NSC
      only group versus controls (p = 0.027, 0.042, respectively). The MSC-only group
      did not demonstrate a significant improvement over control (p = 0.145). Comparing
      the MSC + NSC group and the NSC-only group, there was no significant difference
      (p = 0.357). Subacute transplantation of hNSCs into contused spinal cord of rats
      led to significant functional recovery when injected either with or without acute
      IV administration of hMSCs. Neither hMSCs nor addition of hMSC to hNSC resulted
      in significant improvement. 

PMID- 24436846
TI  - Postoperative pain management after spinal fusion surgery: an analysis of the
      efficacy of continuous infusion of local anesthetics.
AB  - Spinal fusion surgery is a major surgery that results in severe postoperative
      pain, therefore pain reduction is a primary concern. New strategies for pain
      management are currently under investigation and include multimodal treatment. A
      3-year retrospective analysis of patients with idiopathic scoliosis undergoing
      spinal fusion surgery was performed at our hospital, assessing patient pain
      scores, opioid use, and recovery. We evaluated the effect of adding continuous
      infusion of local anesthetics (CILA) to a postoperative pain management protocol
      that includes intraoperative intrathecal morphine, as well as postoperative
      patient-controlled analgesia and oral opioid/acetaminophen combination. The study
      compared 25 patients treated according to the standard protocol, with 62 patients
      treated with CILA in addition to the pain management protocol. Patients in the
      CILA group used nearly 0.5 mg/kg less opioid analgesics during the first 24 hours
      after surgery. 

PMID- 24436847
TI  - Why Are Spine Surgery Patients Lost to Follow-up?
AB  - Long-term outcome studies are frequently hindered by a decreasing frequency of
      patient follow-up with the treating surgeon over time. Whether this attrition
      represents a "loss of faith" in their index surgeon or the realities of a
      geographically mobile society has never been assessed in a population of patients
      undergoing spinal surgery. The purpose of this article is to determine the
      frequency with which patients who have undergone prior surgery and develop new
      problems attempt to follow-up with their index spine surgeon. The study design
      was a population survey. All patients seen at two university-based spine centers
      over a 3-month period were surveyed regarding prior spine surgery. The
      questionnaire asked details of the previous operation, whether the patient had
      sought follow-up with their index surgeon, why the patient did not continue
      treatment with that surgeon, and whether the patient was satisfied with their
      prior treatment. Sixty-nine patients completed the survey. Prior operations were
      lumbar (53 patients) and cervical (16). When asked the reason for not seeing
      their prior surgeon, 10 patients (15%) stated that they (the patient) had moved
      and 16 (23%) responded that their surgeon no longer practiced in the area.
      Thirteen (19%) were unhappy with their previous care, 22 (32%) were seeking a
      second opinion, and 7 (10%) were told they needed more complex surgery. Thirty
      seven (54%) discussed their symptoms with their original surgeon before seeking
      another surgeon. Although 32 patients (46%) had not discussed their new
      complaints with their index surgeon, only 3 patients (4%) chose not to return to
      their prior surgeon despite having the opportunity to do so. Forty-nine patients
      (71%) were satisfied with their prior surgical care, and 42 patients (61%) would
      undergo the index operation again. Most of the patients seen at the authors'
      practices after undergoing prior spine surgery elsewhere failed to follow up with
      their prior spine surgeon for geographical reasons. It appears that the majority
      of patients who develop new spinal complaints will seek out their treating
      surgeon when possible. This suggests that patient attrition over long-term follow
      up may reflect a geographically mobile population rather than patient
      dissatisfaction with prior treatment. 

PMID- 24436848
TI  - Functional outcomes, morbidity, mortality, and fracture healing in 58 consecutive
      patients with geriatric odontoid fracture treated with cervical collar or
      posterior fusion.
AB  - Controversy exists as to the most effective management option for elderly
      patients with type II odontoid fractures. The purpose of this study is to
      evaluate outcomes associated with rigid cervical collar and posterior fusion
      surgery. Patients with >= 50% odontoid displacement were treated with posterior
      fusion surgery including C1-2 (PSF group, n = 25, average age = 80 years).
      Patients with < 50% odontoid displacement were treated with a rigid cervical
      collar for 12 weeks (collar group, n = 33, average age = 83 years). These
      inhomogeneous groups were followed for an average of 14 months. Fracture healing
      rates were higher in the operative group (28% versus 6%). Neck Disability Index
      scores were slightly lower in the nonoperative group (13 versus 18.3, p = 0.23).
      Analogue pain scores were also slightly lower in the nonoperative group (1.3
      versus 1.9, p = 0.26). The mortality rate was 12.5% in the collar group and 20%
      in the operative group. Complications were higher in the operative group (24%
      versus 6%). Rates of type II odontoid facture healing and stability appear to be
      higher in geriatric patients treated with posterior fusion surgery. Fracture
      healing and stability did not correlate with improved outcomes with respect to
      levels of pain, function, and satisfaction. Mortality and complication rates are
      lower in those patients with lesser-displaced fractures who are treated with a
      cervical collar and early mobilization. 

PMID- 24436849
TI  - Extraneural metastasis of ependymoma in the cauda equina.
AB  - We report a rare case of extraneural metastasis of spinal ependymoma that
      developed over a very long period. A 28-year-old man underwent surgery for
      ependymoma in the cauda equina. After he experienced three local recurrences and
      had undergone five operations, a lung metastasis occurred 46 years after the
      first operation. Although the tumor did not show the typical morphological
      malignancy, the maximum standard uptake value obtained by positron-emission
      tomography and the antigen Ki-67 labeling index demonstrated the tumor's active
      proliferative ability. One year after the last operation, the patient died of
      respiratory failure due to progressing lung metastases. The malignant behavior of
      spinal ependymomas is demonstrated in a case with long-term follow-up. 

PMID- 24436850
TI  - Tertiary syphilis in the cervical spine: a case report and review of the
      literature.
AB  - As the prevalence of syphilis rises, an increase in tertiary syphilis with spinal
      involvement is predicted. We report what we believe to be the first case of
      compressive cervical spine syphilitic gummata, with central cord compression
      signs. We also review the relevant literature to date. The diagnosis of syphilis
      in the spine relies on the physician to be aware of it as part of the
      differential diagnosis. Treponemal laboratory tests are an important aid in
      establishing a diagnosis. 

PMID- 24436851
TI  - Arytenoid dislocation as a cause of prolonged hoarseness after cervical
      discectomy and fusion.
AB  - Study Design Case series of two arytenoid dislocations after anterior cervical
      discectomy. Objective To recognize arytenoid dislocation as a possible cause of
      prolonged hoarseness in patients after anterior cervical discectomies. Summary of
      Background Data Prolonged hoarseness is a common postoperative complication after
      anterior cervical spine surgery. The etiology of prolonged postoperative
      hoarseness is usually related to a paresis of the recurrent laryngeal nerve.
      However, other causes of postoperative hoarseness may be overlooked in this
      clinical scenario. Other possible etiologies include pharyngeal and laryngeal
      trauma, hematoma and edema, injury of the superior laryngeal nerve, as well as
      arytenoid cartilage dislocation. Arytenoid dislocation is often misdiagnosed as
      vocal fold paresis due to recurrent or laryngeal nerve injury. Methods We report
      two cases of arytenoid dislocation and review the literature on this pathology.
      Results Two patients treated with anterior cervical discectomy and fusion
      experienced prolonged postoperative hoarseness. Arytenoid dislocation was
      confirmed by flexible fiber-optic laryngoscopy in both cases. The dislocations
      experienced spontaneous reduction at 6 weeks and 3 months postsurgery.
      Conclusions Arytenoid dislocation must be considered in the differential
      diagnosis of prolonged postoperative hoarseness and evaluated for using direct
      laryngoscopy, computed tomography, or a laryngeal electromyography. Upon
      diagnosis, treatment must be considered immediately. Slight dislocations can
      reduce spontaneously without surgical intervention; however, operative
      intervention may be required at times. 

PMID- 24436853
TI  - Determining optimal c2 pedicle screw placement and length in patients with axis
      traumatic spondylolisthesis: a case series.
AB  - We sought to determine the optimal placement and screw length for C2 pedicle
      screw fixation to compare with recommendations in literature. Nine patients were
      included in this study and underwent C2 pedicle instrumentation either for a
      hangman's fracture as part of C2 pedicle-C3 lateral mass fixation or for C2-C3
      subluxation. All nine patients had good postoperative improvement with
      satisfactory fracture consolidation. Mediolateral and rostrocaudal angulations of
      the inserted screws were not consistent with the traditional angulations of 20
      degrees in each plane due to the fracture lines and the anatomical variations.
      Because the frequent observation of the bony anatomical variations and the lines
      of fractures brought about by trauma, a shift from the classic 20 degrees of
      angulation in both trajectories has been concluded. But still fixed angles of
      angulations cannot be generalized. As a consequence, accurate preoperative
      planning can be obtained by computed tomography with three-dimensional images so
      that it gives the surgeon a good prediction of the best length of utilized screws
      in the procedure and the best angulations for safety of the neighboring
      neurovascular structures. 

PMID- 24436852
TI  - Current status of adult spinal deformity.
AB  - Purpose To review the current literature for the nonoperative and operative
      treatment for adult spinal deformity. Recent Findings With more than 11 million
      baby boomers joining the population of over 60 years of age in the United States,
      the incidence of lumbar deformity is greatly increasing. Recent literature
      suggests that a lack of evidence exists to support the effectiveness of
      nonoperative treatment for adult scoliosis. In regards to operative treatment,
      current literature reports a varying range of improved clinical outcomes, curve
      correction, and complication rates. The extension of fusion to S1 compared with
      L5 and lower thoracic levels compared with L1 remains a highly controversial
      topic among literature. Summary Most adult deformity patients never seek
      nonoperative or operative treatment. Of the few that seek treatment, many can
      benefit from nonoperative treatment. However, in selected patients who have
      failed nonoperative treatment and who are candidates for surgical intervention,
      the literature reflects positive outcomes related to surgical intervention as
      compared with nonoperative treatment despite varying associated ranges in
      morbidity and mortality rates. If nonoperative therapy fails in addressing a
      patient's complaints, then an appropriate surgical procedure that relieves neural
      compression, corrects excessive sagittal or coronal imbalance, and results in a
      solidly fused, pain-free spine is warranted. 

PMID- 24436855
TI  - Epidemiological trends of spine trauma: an Australian level 1 trauma centre
      study.
AB  - Knowledge of current epidemiology and spine trauma trends assists in public
      resource allocation, fine-tuning of primary prevention methods, and benchmarking
      purposes. Data on all patients with traumatic spine injuries admitted to the
      Alfred Hospital, Melbourne between May 1, 2009, and January 1, 2011, were
      collected from the Alfred Trauma Registry, Alfred Health medical database, and
      Victorian Orthopaedic Trauma Outcomes Registry. Epidemiological trends were
      analyzed as a general cohort, with comparison cohorts of nonsurvivors versus
      survivors and elderly versus nonelderly. Linear regression analysis was utilized
      to demonstrate trends with statistical significance. There were 965 patients with
      traumatic spine injuries with 2,333 spine trauma levels. The general cohort
      showed a trimodal age distribution, male-to-female ratio of 2:2, motor vehicle
      accidents as the primary spine trauma mechanism, 47.7% patients with severe
      polytrauma as graded using the Injury Severity Score (ISS), 17.3% with traumatic
      brain injury (TBI), the majority of patients with one spine injury level, 7%
      neurological deficit rate, 12.8% spine trauma operative rate, and 5.2% mortality
      rate. Variables with statistical significance trending toward mortality were the
      elderly, motor vehicle occupants, severe ISS, TBI, C1-2 dissociations, and
      American Spinal Injury Association (ASIA) A, B, and C neurological grades.
      Variables with statistical significance trending toward the elderly were females;
      low falls; one spine injury level; type 2 odontoid fractures; subaxial cervical
      spine distraction injuries; ASIA A, B, and C neurological grades; and patients
      without neurological deficits. Of the general cohort, 50.3% of spine trauma
      survivors were discharged home, and 48.1% were discharged to rehabilitation
      facilities. This study provides baseline spine trauma epidemiological data. The
      trimodal age distribution of patients with traumatic spine injuries calls for
      further studies and intervention targeted toward the 46- to 55-year age group as
      this group represents the main providers of financial and social security. The
      study's unique feature of delineating variables with statistical significance
      trending toward both mortality and the elderly also provides useful data to guide
      future research studies, benchmarking, public health policy, and efficient
      resource allocation for the management of spine trauma. 

PMID- 24436854
TI  - Dynamic changes of the ligamentum flavum in the cervical spine assessed with
      kinetic magnetic resonance imaging.
AB  - The purpose of this article is to quantify changes in thickness of the ligamentum
      flavum (LF) associated with motion of the cervical spine and to compare the
      thickness of the LF at each cervical level using kinetic magnetic resonance
      imaging (kMRI). Two hundred fifty-seven symptomatic patients (129 men; 128 women)
      underwent kMRI in neutral, flexion, and extension positions. Midsagittal images
      were digitally marked and electronically analyzed by spine surgeons. Thickness of
      LF in the cervical region from C2-3 to C7-T1 was measured in all three positions.
      LF at C7-T1 was significantly thicker than C2-3 to C6-7 in neutral, flexion, and
      extension positions (p < 0.05). LF was significantly thicker in extension than in
      flexion at C3-4 to C6-7. LF thickness increases with extension and decreases with
      flexion. LF is uniquely thick at C6-7 and at C7-T1 in the extension position,
      which may predispose these levels to cord compression syndromes and associated
      neuropathies. 

PMID- 24436856
TI  - Finite Element Analysis and Biomechanical Comparison of Short Posterior Spinal
      Instrumentation with Divergent Bridge Construct versus Parallel Tension Band
      Construct for Thoracolumbar Spine Fractures.
AB  - The ideal treatment for unstable thoracolumbar fractures remains controversial
      with posterior reduction and stabilization, anterior reduction and stabilization,
      combined posterior and anterior reduction and stabilization, and even
      nonoperative management advocated. Short segment posterior osteosynthesis of
      these fractures has less comorbidities compared with the other operative
      approaches but settles into kyphosis over time. Biomechanical comparison of the
      divergent bridge construct versus the parallel tension band construct was
      performed for anteriorly destabilized T11-L1 spine segments using three different
      models: (1) finite element analysis (FEA), (2) a synthetic model, and (3) a human
      cadaveric model. Outcomes measured were construct stiffness and ultimate failure
      load. Our objective was to determine if the divergent pedicle screw bridge
      construct would provide more resistance to kyphotic deforming forces. All three
      modalities showed greater stiffness with the divergent bridge construct. The FEA
      calculated a stiffness of 21.6 N/m for the tension band construct versus 34.1 N/m
      for the divergent bridge construct. The synthetic model resulted in a mean
      stiffness of 17.3 N/m for parallel tension band versus 20.6 N/m for the divergent
      bridge (p = 0.03), whereas the cadaveric model had an average stiffness of 15.2
      N/m in the parallel tension band compared with 18.4 N/m for the divergent bridge
      (p = 0.02). Ultimate failure load with the cadaveric model was found to be 622 N
      for the divergent bridge construct versus 419 N (p = 0.15) for the parallel
      tension band construct. This study confirms our clinical experience that the
      short posterior divergent bridge construct provides greater stiffness for the
      management of unstable thoracolumbar fractures. 

PMID- 24436857
TI  - Postoperative deep surgical-site infection after instrumented spinal surgery: a
      multicenter study.
AB  - A retrospective survey revealed 37 cases (1.1%) of deep surgical-site infection
      (SSI) among 3,462 instrumented spinal surgeries between 2004 and 2008. Excluding
      8 patients who were unclassifiable, we categorized 29 patients into 3 groups of
      similar backgrounds-thoracolumbar degenerative disease (the DEG group; n = 15),
      osteoporotic vertebral collapse (the OVC group; n = 10), and cervical disorders
      (the cervical group; n = 4)-and investigated the key to implant salvage. Final
      respective implant retention rates for the groups were 40, 0, and 100%, with the
      OVC group having the worst rate (p < 0.01). In the DEG group with early
      infection, those whose implants were retained had lower body temperatures, lower
      white blood cell counts, and a lower rate of discharge at the time of SSI
      diagnosis (p < 0.05). Implant retention may be affected by initial spinal
      pathology. In the DEG group, debridement before drainage may be advantageous to
      implant salvage. 

PMID- 24436859
TI  - Treatment of combined spinal deformity in patient with ollier disease and
      abnormal vertebrae.
AB  - We report staged treatment of severe combined spinal deformity in an 11-year-old
      patient with Ollier disease and abnormal cervical vertebra. Combined scoliosis
      with systemic pathology and abnormal vertebrae is a rare condition and features
      atypical deformity location and rapid progression rate and frequently involves
      the rib cage and pelvis, disturbing the function of chest organs and skeleton.
      Progressive deformity resulted in cachexia and acute respiratory failure. A halo
      pelvic distraction device assembled of Ilizarov components was employed for a
      staged surgical treatment performed for lifesaving indications. After vital
      functions stabilized, the scoliosis curve of the cervical spine was corrected and
      fixed with a hybrid system of transpedicular supporting points, connecting rods,
      and connectors that provided staged distraction during growth. The treatment
      showed good functional and cosmetic result. 

PMID- 24436858
TI  - Accuracy of intraoperative computed tomography-based navigation for placement of
      percutaneous pedicle screws.
AB  - MISS techniques have gained recent popularity. The proposed benefits of these
      techniques include reduced tissue trauma, reduced blood loss, less perioperative
      pain, and a quicker recovery and return to normal activities. The purpose of this
      study was to evaluate the accuracy of intraoperative computed tomography (CT)
      based navigation for placement of percutaneous pedicle screws in a cadaveric
      model. Outcome measures included accuracy of screw placement. Two cadaveric
      specimens were utilized. CT images were obtained using an O-Arm (Medtronic,
      Memphis, Tennessee, United States) and were coupled to the Stealth navigation
      system (Medtronic). Computer navigation was used for placement of percutaneous
      pedicle screws. Screws were placed bilaterally from T5 to S1. Postinsertion CT
      scans were obtained. Pedicle breach was assessed and classified (I: none, II: < 2
      mm, III: 2 to 4 mm, or IV: > 4 mm) with direction of breach. Thirty thoracic
      screws were placed with 3 (10%) medial breaches and 17 (56.7%) lateral breaches
      (grade III). Of 20 lumbar screws there were 0 medial breaches and 2 (10%) lateral
      breaches (1 grade III, 1 grade IV). Four sacral screws were placed without
      breaches. The real-time computer-aided navigation tool ("simulated screw") was
      limited in identifying a breach. Manipulation of the surgeon's hand or driver
      could change the orientation of the navigation tool without changing the screw
      trajectory. CT-based navigation for percutaneous pedicle screw placement appears
      safe for the lumbar spine. Lateral thoracic breaches appeared commonly but were
      not felt to be clinically significant. The 10% rate of medial thoracic breach was
      concerning, but definitive conclusions could not be made due to the small sample
      size. 

PMID- 24436860
TI  - "Globus symptoms": a rare case of giant osteochondroma of the axis treated with
      high cervical extrapharyngeal approach.
AB  - Background Osteochondroma is the most common primary bone tumor, composing 35% of
      benign bone tumors and 9% of all bone tumors; 1.3 to 4.1% of all osteochondromas
      originate from the spine. A rare differential diagnosis for globus symptoms is an
      osteochondroma originating from the anterior surface of the axis. We describe a
      rare case of osteochondroma of the dens resulting in "globus symptoms" (the
      subjective sensation of a mass in the throat) treated with excision via the high
      cervical extrapharyngeal approach. Purpose To discuss the surgical management of
      this problem, with an emphasis on surgical approach used. The clinical history,
      examination, and investigations are presented and illustrated, along with
      clinical patient outcome. Study Design/Setting This article is a case report of a
      patient treated at the Department of Trauma and Orthopaedics in an active
      university teaching hospital. Methods Case presentation. For the discussion, we
      used handpicked articles, as well as MEDLINE and PubMed database searches with
      the keywords "C2," "dens," "osteochondroma," "globus," "extrapharyngeal
      approach." Results Uncomplicated procedure. Histological analysis confirmed a
      benign osteochondroma with no evidence of malignancy. The patient underwent an
      uncomplicated postoperative recovery and was discharged 24 hours after surgery,
      fully ambulatory and eating and drinking well. Conclusions The high cervical
      retropharyngeal approach is safe and reproducible for the excision of
      osteochondromas or osteophytes of the upper cervical spine. 

PMID- 24436862
TI  - Disk degeneration and pain.

PMID- 24436861
TI  - Subarachnoid hemorrhage from a thoracic radicular artery pseudoaneurysm after
      methamphetamine and synthetic cannabinoid abuse: case report.
AB  - Background Context Isolated spinal artery aneurysms not associated with vascular
      malformations are exceedingly rare. Purpose To present a rare case of
      subarachnoid hemorrhage after thoracic radiculomedullary artery pseudoaneurysm
      rupture in a patient who abused synthetic cannabinoids and methamphetamines.
      Study Design Case report. Methods A 41-year-old man with a history of
      polysubstance abuse presented with acute-onset headache, back pain, and transient
      bilateral lower-extremity numbness. He reported daily use of the synthetic
      cannabinoid "Spice." He denied use of other illegal drugs, but laboratory testing
      was positive for methamphetamines. Magnetic resonance imaging showed a focal
      hematoma at T2-3, and spinal angiography was negative for vascular abnormalities;
      however, a follow-up angiogram 6 days later revealed interval development of an
      irregular dilation of the left T3 radiculomedullary artery originating from the
      left supreme intercostal artery. Results Surgical trapping and resection of the
      lesion yielded a good clinical outcome. Conclusions Although two previous case
      reports have described patients with thoracic radiculomedullary pseudoaneurysm
      causing spinal subarachnoid hemorrhage (SAH), this is the first reported case
      associated with synthetic cannabinoids and methamphetamine abuse. Although this
      diagnosis is exceptionally rare, clinical presentation of SAH with associated
      back pain and lower-extremity symptoms warrants an aggressive imaging workup.
      Even in the setting of negative angiography, repeat cerebral and spinal
      angiograms may be necessary to identify a potentially treatable cause of spinal
      SAH. 

PMID- 24436863
TI  - Novel imaging of the intervertebral disk and pain.
AB  - T-1-rho (T1rho) magnetic resonance imaging (MRI) and disc height ratio (DHR) are
      potential biomarkers of degenerative disk disease (DDD) related to biochemical
      composition and morphology of the intervertebral disk (IVD), respectively. To
      objectively detect DDD at an early stage, the hypothesis was tested that the
      average T1rho relaxation time of the nucleus pulposus (NP) correlates with the
      disk height of degenerate IVDs, measured by MRI. Studies were performed on a 3-T
      Siemens Tim Trio clinical MRI scanner (Siemens Healthcare, Malvern, Pennsylvania,
      United States) on patients being treated for low back pain whose disks were
      categorized into (1) painful and (2) nonpainful subgroups based on provocative
      diskography and (3) age-matched healthy controls. Painful disks presented both
      low DHR and T1rho values, nonpainful disks measured the highest DHR and extended
      to a higher range of T1rho, and control disks presented a midrange DHR with the
      highest T1rho values. T1rho MRI evaluated in the NP of IVDs may be useful to
      establish a threshold (120 milliseconds here) above which indicates a healthy
      disk, and disks measuring low NP T1rho (50 to 120 milliseconds here) would
      require disk height analysis to further categorize the disk. Combining T1rho MRI
      and disk height analysis may hold promise in predicting painful disks without
      provocative diskography, and predictive models should be developed. 

PMID- 24436864
TI  - Disk degeneration and low back pain: are they fat-related conditions?
AB  - Low back pain (LBP) is the world's most debilitating condition. Disk degeneration
      has been regarded as a strong determinant associated with LBP. Overweight and
      obesity are public health concerns that affect every population worldwide and
      whose prevalence continues to rise. Studies have indicated strong associations
      between overweight/obesity and disk degeneration as well as with LBP. This broad
      narrative review article addresses the various mechanisms that may be involved
      leading to disk degeneration and/or LBP in the setting of overweight/obesity. In
      particular, our goal is to raise awareness of the role of fat cells and their
      involvement via altered metabolism or the release of adipokines as well as other
      pathways that may lead to the development of disk degeneration and LBP.
      Understanding the role of fat in this process may aid in the development of novel
      biological therapies and technologies to halt the progression or regenerate the
      disk. Moreover, with genetic advancements and the appreciation of genetic
      epidemiology, a more personalized approach to spine care may have to consider the
      role of fat in any preventative, therapeutic, and/or prognosis modalities toward
      the disk and LBP. 

PMID- 24436865
TI  - Mechanisms of intervertebral disk degeneration/injury and pain: a review.
AB  - Degeneration of the intervertebral disk and its treatments are currently
      intensely investigated topics. Back pain is a condition whose chronic and
      debilitating nature combined with its prevalence make it a major health issue of
      substantial socioeconomic importance. Although researchers, and even sometimes
      clinicians, focus on the degenerated disk as the problem, to most patients, pain
      is the factor that limits their function and impacts their well-being. The
      purpose of this review is to delineate the changes associated with disk
      degeneration and to outline mechanisms by which they could be the source of back
      pain. Although the healthy disk is only innervated in the external layer of its
      annulus fibrosus, adjacent structures are plentiful with nociceptive receptors.
      Stimulation of such structures as a consequence of processes initiated by disk
      degeneration is explored. The concept of discogenic pain and possible mechanisms
      such as neoinnervation and solute transport are discussed. Finally, how such pain
      mechanisms may relate to current and proposed treatment strategies is discussed. 

PMID- 24436866
TI  - The role of the vertebral end plate in low back pain.
AB  - End plates serve as the interface between rigid vertebral bodies and pliant
      intervertebral disks. Because the lumbar spine carries significant forces and
      disks don't have a dedicated blood supply, end plates must balance conflicting
      requirements of being strong to prevent vertebral fracture and porous to
      facilitate transport between disk cells and vertebral capillaries. Consequently,
      end plates are particularly susceptible to damage, which can increase
      communication between proinflammatory disk constituents and vascularized
      vertebral bone marrow. Damaged end plate regions can be sites of reactive bone
      marrow lesions that include proliferating nerves, which are susceptible to
      chemical sensitization and mechanical stimulation. Although several lines of
      evidence indicate that innervated end plate damage can be a source of chronic low
      back pain, its role in patients is likely underappreciated because innervated
      damage is poorly visualized with diagnostic imaging. This literature review
      summarizes end plate biophysical function and aspects of pathologic degeneration
      that can lead to vertebrogenic pain. Areas of future research are identified in
      the context of unmet clinical needs for patients with chronic low back pain. 

PMID- 24436867
TI  - Cell signaling pathways related to pain receptors in the degenerated disk.
AB  - Many of the causes of low back pain are still unknown; sufficient evidence
      indicates that both degenerative and mechanical change within the intervertebral
      disk (IVD) is a relevant factor. This article reviews intracellular signaling
      pathways related to pain receptors in the degenerated IVD. Several reports have
      demonstrated the number of nerve fibers in the IVD was increased in degenerated
      disks. In recent years, some groups have reported that an increase in nerve
      fibers is associated with the presence of inflammatory mediators and/or
      neurotrophins in the IVD. Cell signaling events, which are regulated by
      inflammatory mediators and neurotrophins, must be identified to clarify the
      mechanism underlying low back pain. Major intracellular signaling pathways
      (nuclear factor kappa beta, mitogen-activated protein kinases, and Wnts)
      potentially play vital roles in mediating the molecular events responsible for
      the initiation and progression of IVD degeneration. These signaling pathways may
      represent therapeutic targets for the treatment of IVD degeneration and its
      associated back pain. 

PMID- 24436868
TI  - Inflammatory mediators in intervertebral disk degeneration and discogenic pain.
AB  - Although degeneration of the intervertebral disk has historically been described
      as a misbalance between anabolic and catabolic factors, the role of inflammatory
      mediators has long been neglected. However, past research clearly indicates that
      inflammatory mediators such as interleukin (IL)-1beta, IL-6, IL-8 and tumor
      necrosis factor-alpha are expressed at higher levels in "diseased" intervertebral
      disks. Both disk cells as well as invading macrophages can be the source of the
      detected cytokines. Importantly, occurrence of inflammatory mediators in the disk
      can worsen the progress of degeneration by inducing the expression of matrix
      degrading enzymes as well as by inhibiting extracellular matrix synthesis. In
      addition, inflammatory mediators play a crucial role in pain development during
      intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e.,
      discogenic pain). This review provides information on the most relevant
      inflammatory mediators during different types of disk diseases and explains how
      these factors can induce disk degeneration and the development of discogenic and
      sciatic/radiculopathic pain. 

PMID- 24436869
TI  - Molecular therapy for disk degeneration and pain.
AB  - The nucleus pulposus of the intervertebral disk contains high amounts of the
      proteoglycan aggrecan, which confers the disk with a remarkable ability to resist
      compression. Other molecules such as collagens and noncollagenous proteins in the
      extracellular matrix are also essential for function. During disk degeneration,
      aggrecan and other molecules are lost due to proteolysis. This can result in loss
      of disk height, which can ultimately lead to pain. Biological therapy of
      intervertebral disk degeneration aims at preventing or restoring primarily
      aggrecan content and other molecules using therapeutic molecules. The purpose of
      the article is to review recent advances in biological repair of degenerate disks
      and pain. 

PMID- 24436870
TI  - Biologically based therapy for the intervertebral disk: who is the patient?
AB  - The intervertebral disk (IVD) is a fascinating and resilient tissue compartment
      given the myriad of functions that it performs as well as its unique anatomy. The
      IVD must tolerate immense loads, protect the spinal cord, and contribute
      considerable flexibility and strength to the spinal column. In addition, as a
      consequence of its anatomical and physiological configuration, a unique
      characteristic of the IVD is that it also provides a barrier to metastatic
      disease. However, when injured and/or the subject of significant degenerative
      change, the IVD can be the source of substantial pain and disability.
      Considerable efforts have been made over the past several decades with respect to
      regenerating or at least modulating degenerative changes affecting the IVD
      through the use of many biological agents such as growth factors, hydrogels, and
      the use of plant sterols and even spices common to Ayurvedic medicine. More
      recently stem/progenitor and autologous chondrocytes have been used mostly in
      animal models of disk disease but also a few trials involving humans. At the end
      of the day if biological therapies are to offer benefit to the patient, the
      outcomes must be improved function and/or less pain and also must be improvements
      upon measures that are already in clinical practice. Here some of the challenges
      posed by the degenerative IVD and a summary of some of the regenerative attempts
      both in vitro and in vivo are discussed within the context of the vital question:
      "Who is the patient?" 

PMID- 24436872
TI  - Symptomatic adjacent segment pathology after posterior lumbar interbody fusion
      for adult low-grade isthmic spondylolisthesis.
AB  - The incidence of symptomatic adjacent segment pathology (ASP) after fusion
      surgery for adult low-grade isthmic spondylolisthesis (IS) has been reported to
      be relatively low compared with other lumbar disease entities. However, there has
      been no study of symptomatic ASP incidence using posterior lumbar interbody
      fusion (PLIF) with pedicle screw instrumentation. We investigated the incidence
      of symptomatic ASP after PLIF with pedicle screw instrumentation for adult low
      grade IS and identified significant risk factors for symptomatic ASP. We
      retrospectively studied records of 40 consecutive patients who underwent PLIF
      with pedicle screw instrumentation at the Department of Orthopaedic Surgery,
      Kansai Rosai Hospital, Amagasaki, Japan. The patients were followed for >= 4
      years. Patients' medical records were retrospectively examined for evidence of
      symptomatic ASP. Age at time of surgery, sex, fusion level, whole lumbar
      lordosis, segmental lordosis, preexisting laminar inclination angle, and facet
      tropism at the cranial fusion segment were analyzed to identify risk factors for
      symptomatic ASP. Four patients (ASP group) developed symptomatic ASP at the
      cranial segment adjacent to the fusion. There were no significant differences in
      age, sex, fusion level, lumbar lordosis, segmental lordosis, or facet tropism at
      the cranial segment adjacent to the fusion between the ASP and the non-ASP
      groups. In contrast, laminar inclination angle at the cranial vertebra adjacent
      to the fusion was significantly higher in the ASP group than in the non-ASP
      group. Four patients (10%) developed symptomatic ASP after PLIF with
      transpedicular fixation for adult low-grade IS. Preexisting laminar
      horizontalization at the cranial vertebra adjacent to the fusion was a
      significant risk factor for symptomatic ASP. 

PMID- 24436873
TI  - Bilateral Pedicle Screw Fixation versus Unilateral Pedicle and Contralateral
      Facet Screws for Minimally Invasive Transforaminal Lumbar Interbody Fusion:
      Clinical Outcomes and Cost Analysis.
AB  - Study Design Retrospective clinical study. Objectives Recent biomechanical
      studies have shown no differences in stiffness or range of motion following
      minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) between
      unilateral pedicle and contralateral facet screw (UPFS) and bilateral pedicle
      screw (BPS) constructs. No studies have compared these two constructs based upon
      clinical outcomes. Methods Twenty-six consecutive patients who had single-level
      MIS TLIF were retrospectively reviewed. Outcome measures collected for patients
      with BPS were compared with those with UPFS. Results No associations were found
      between construct and length of stay (p = 0.5), operative time (p = 0.2), or
      Odom's criteria (p = 0.7); 79% of patients in the UPFS group as compared with
      71.5% in the BPS group had good or excellent outcomes. Mean follow-up was 17.7
      months for the UPFS group and 20.2 months for the BPS group. There was one
      complication in each group, including a seroma in the BPS group and a revision
      operation in the UPFS group. Implant costs for the BPS group were 35% greater
      than the UPFS group. Conclusions The present study is the first to demonstrate
      that patients undergoing MIS TLIF with BPS as compared with UPFS for single-level
      degenerative lumbar disease had similar clinical outcomes. 

PMID- 24436874
TI  - Hypovitaminosis D and Cervical Disk Herniation among Adults Undergoing Spine
      Surgery.
AB  - Study Design Single-center, retrospective study. Objective Suboptimal
      concentrations of vitamin D have been linked to hip and knee osteoarthritis in
      large, population-based cohort studies. We sought to examine the association of
      vitamin D levels with intervertebral disk disease. Methods From January 2010
      through May 2011, 91 consecutive, eligible adult spine surgery patients who had
      undergone cervical magnetic resonance imaging (MRI) and preoperative serum 25
      hydroxyvitamin D (s25D) measurement were retrospectively included. MRI was read
      for C2-T1 disk herniation and degeneration (grades I to V). Logistic regressions
      were performed. Results Compared with the 384 disks of nondeficient patients, 162
      disks of vitamin D-deficient (< 20 ng/mL) patients were more frequently herniated
      (40% versus 27%, p = 0.004); deficiency was not predictive of individual disk
      grade (unadjusted odds ratio [uOR] = 0.98, p = 0.817). On regression analysis,
      deficiency was associated with increased number of herniations per patient (uOR =
      2.17, 95% confidence interval [CI] = 1.22 to 3.87, p = 0.009; adjusted odds ratio
      [aOR] = 2.12, 95% CI = 1.11 to 4.03, p = 0.023). When disks were analyzed
      individually, and levels (e.g., C5 to C6), additionally controlled for,
      deficiency correlated with greater likelihood of herniation per disk (uOR = 1.81,
      95% CI = 1.22 to 2.66, p = 0.003; aOR = 2.06, 95% CI = 1.25 to 3.41, p = 0.005).
      Conclusion Among adults undergoing spine surgery at our institution, vitamin D
      deficiency was associated with cervical disk herniation. Considering the current
      epidemics of vitamin D insufficiency and neck pain, further investigation is
      warranted, as these data were retrospectively collected and subject to sampling
      bias. 

PMID- 24436871
TI  - Notochordal cell-derived therapeutic strategies for discogenic back pain.
AB  - An understanding of the processes that occur during development of the
      intervertebral disk can help inform therapeutic strategies for discogenic pain.
      This article reviews the literature to identify candidates that are found in or
      derived from the notochord or notochordal cells and evaluates the theory that
      such factors could be isolated and used as biologics to target the structural
      disruption, inflammation, and neurovascular ingrowth often associated with
      discogenic back pain. A systematic review using PubMed was performed with a
      primary search using keywords "(notochordal OR notochord) And (nerves OR blood
      vessels OR SHH OR chondroitin sulfate OR notch OR CTGF) NOT chordoma." Secondary
      searches involved keywords associated with the intervertebral disk and pain.
      Several potential therapeutic candidates from the notochord and their possible
      targets were identified. Studies are needed to further identify candidates,
      explore mechanisms for effect, and to validate the theory that these candidates
      can promote structural restoration and limit or inhibit neurovascular ingrowth
      using in vivo studies. 

PMID- 24436875
TI  - Single-level degenerative cervical disc disease and driving disability: results
      from a prospective, randomized trial.
AB  - Study Design Post hoc analysis of prospective, randomized trial. Objective To
      investigate the disability associated with driving and single-level degenerative,
      cervical disc disease and to investigate the effect of surgery on driving
      disability. Methods Post hoc analysis of data obtained from three sites
      participating in a multicenter, randomized, controlled trial comparing cervical
      disc arthroplasty (TDA) with anterior cervical discectomy and fusion (ACDF). The
      driving subscale of the Neck Disability Index (NDI) was analyzed for all
      patients. A dichotomous severity score was created from the NDI. Statistical
      comparisons were made within and between groups. Results Two-year follow-up was
      available for 118/135 (87%) patients. One half of the study population (49.6%)
      reported moderate or severe preoperative driving difficulty. This disability
      associated with driving was similar among the two groups (ACDF: 2.5 +/- 1.1, TDA:
      2.6 +/- 1.0, p = 0.646). The majority of patients showed improvement, with no or
      little driving disability, at the sixth postoperative week (ACDF: 75%, TDA: 90%,
      p = 0.073). At no follow-up point did a difference exist between groups according
      to the severity index. Conclusions Many patients suffering from radiculopathy or
      myelopathy from cervical disc disease are limited in their ability to operate an
      automobile. Following anterior cervical spine surgery, most patients are able to
      return to comfortable driving at 6 weeks. 

PMID- 24436876
TI  - Anatomic variability of 120 L5 spondylolytic defects.
AB  - Study Design Adult human osteologic specimens were assessed for spondylolytic
      defects and characterized. Objectives To characterize and determine the
      prevalence of spondylolytic defects in an osteological collection. Methods Lumbar
      vertebrae from the Hamann-Todd Osteological Collection at the Cleveland Museum of
      Natural History were examined. Digital images of specimens with L5 isthmic
      spondylolytic defects were analyzed, examining the distance of the pars defect in
      the sagittal plane in relation to the caudal aspect of the pedicle. Results There
      were 95 bilateral complete (BC), 16 unilateral incomplete (UI), 5 unilateral
      complete (UC), and 4 unilateral complete defects with an incomplete defect on the
      contralateral side. The mean distance of BC defects from the pedicle and inferior
      vertebral end plate was 4.03 mm and 4.88 mm, respectively. The mean distance of
      the defect from the inferior end plate on the left and right sides were 5.31 mm
      and 4.44 mm, respectively (p = 0.001, correlation coefficient = 0.56). The mean
      distance of UI and UC defects from the inferior end plate was 6.38 mm and 2.6 mm,
      respectively. Conclusion L5 spondylolytic defects were found in 3.87% of the
      sample. This large-scale description of isthmic spondylolytic defects reveals
      that significant variability exists in the location of the defect. The anatomic
      location of the pars defect likely plays a role in the development of L5 nerve
      root compression and radiculopathy in this clinical scenario. Classifying these
      defects might allow surgeons to better identify those patients who might benefit
      from fusion alone without posterior decompression. 

PMID- 24436877
TI  - Cervical intradural abscess masquerading as an epidural collection.
AB  - Intradural spinal cord abscesses especially in the cervical spine are a rare
      occurrence. We report a rare presentation of an intradural extramedullary abscess
      at the atlantoaxial level, initially misdiagnosed as an epidural collection. The
      patient presented with worsening quadriparesis preceded by a 2-week history of
      upper respiratory tract infection and neck pain. Magnetic resonance imaging
      showed evidence of an epidural abscess on the left side abutting the
      cervicomedullary junction. We performed occipitocervical fixation and surgical
      decompression. Absence of a suspected epidural abscess led us to consider a
      durotomy, and an intradural abscess was recognized and drained. Presence of an
      intradural abscess, though extremely rare, must always be considered in suspected
      spinal epidural collections as radiological and clinical findings are
      indistinguishable between the two conditions. 

PMID- 24436878
TI  - Failure of a carbon fiber-reinforced polymer implant used for transforaminal
      lumbar interbody fusion.
AB  - Lumbar interbody fusion is a common procedure owing to the high prevalence of
      degenerative spinal disorders. During such procedures, carbon fiber-reinforced
      polymer (CFRP) cages are frequently utilized to fill the void created between
      adjacent vertebral bodies, to provide mechanical stability, and to carry graft
      material. Failure of such implants can lead to significant morbidity. We discuss
      the possible causes leading to the failure of a CFRP cage in a patient with
      rheumatoid arthritis. Review of a 49-year-old woman who underwent revision
      anterior lumbar interbody fusion 2 years after posterior instrumentation and
      transforaminal lumbar interbody fusion at L4-L5 and L5-S1. The patient developed
      pseudarthrosis at the two previously fused levels with failure of the posterior
      instrumentation. Revision surgery reveled failure with fragmentation of the CFRP
      cage at the L5-S1 level. CFRP implants can break if mechanical instability or
      nonunion occurs in the spinal segments, thus emphasizing the need for optimizing
      medical management and meticulous surgical technique in achieving stability. 

PMID- 24436879
TI  - Central diabetes insipidus after staged spinal surgery.
AB  - Diabetes insipidus (DI) is described following penetrating spinal cord trauma but
      rarely following instrumented spinal fusion. More commonly, hyponatremia is seen
      following spine surgery, which may be iatrogenic, attributed to the syndrome of
      inappropriate antidiuretic hormone release. The authors present a case of a 57
      year-old woman who underwent a planned two-stage operation for scoliotic
      deformity correction. On the third postoperative day, the patient developed
      hypernatremia (sodium levels of 157 mmol/L) and polyuria. In conjunction with
      endocrinology, the patient was diagnosed with central DI. The patient was treated
      with desmopressin acetate (DDAVP), which led to resolution of her symptoms. DDAVP
      was temporary and eventually weaned off. Central DI is a possible cause of
      hypernatremia following significant spine surgery. Correct diagnosis is paramount
      for rapid and appropriate treatment. 

PMID- 24436880
TI  - Primary spinal marginal zone lymphoma relapse at a different spinal level after
      remission of the primary lesion.
AB  - Study Design Case report. Objective Most spinal lymphomas occur in the context of
      systematic lymphomas. Marginal zone lymphoma (MZL) is a type of B-cell lymphoma
      originating from the marginal zone of B-cell follicles. Mucosa-associated
      lymphoid tissue (MALT) lymphoma is a type of extranodal MZL and rarely occurs in
      the central nervous system. To date, there has been only one case report of
      primary spinal MALT lymphoma and there are no case reports of relapsed MALT
      lymphoma at a different location of the spine. Results A 58-year-old man
      complained of gait disturbance and urinary dysfunction. Magnetic resonance images
      showed an abnormal lesion in the epidural space at T11-L1 compressing the conus
      medullaris. The patient underwent laminectomy and partial resection of the tumor.
      Histopathologic and immunohistochemical findings were consistent with MALT
      lymphoma. Following postoperative radiotherapy, the epidural mass disappeared
      completely. Three years later, epidural MALT lymphoma at a different location in
      the thoracic spine (T8-T10) occurred and caused myelopathy again. Histologic
      diagnosis of the relapsed tumor was the same as had been seen 3 years previously.
      Conclusions This is the first case report of relapsed spinal MALT lymphoma at a
      different location of the thoracic spine. Though the prognosis of MALT lymphoma
      is fairly good, careful follow-up is needed to screen any relapse or
      transformation to a high-grade lymphoma. 

PMID- 24436881
TI  - Dedicated spine trauma clinical quality registries: a systematic review.
AB  - Study Design Systematic review. Objective We assessed the current state of spine
      registries by collecting spine trauma data and assessing their compliance to
      defined registry standards of being clinical quality. We ascertained if these
      registries collected spinal cord injury data alone or with spine column trauma
      data. Methods A systematic review was performed using MEDLINE and Embase
      databases for articles describing dedicated spinal cord and spine column
      databases published between January 1990 and April 2011. Correspondence with
      these registries was performed via e-mail or post. When no correspondence was
      possible, the registries were analyzed with best information available. Results
      Three hundred eight full-text articles were reviewed. Of 41 registries
      identified, 20 registries fulfilled the criteria of being clinical quality. The
      main reason for failure to attain clinical quality designation was due to the
      unavailability of patient outcomes. Eight registries collected both spine column
      and spinal cord injury data with 33 collecting only traumatic spinal cord injury
      data. Conclusion There is currently a paucity of clinical quality spine trauma
      registries. Clinical quality registries are important tools for demonstrating
      trends and outcomes, monitoring care quality, and resolving controversies in the
      management of spine trauma. An international spine trauma data set (containing
      both spinal cord and spine column injury data) and standardized approach to
      recording and analysis are needed to allow international multicenter
      collaboration and benchmarking. 

PMID- 24436882
TI  - Oropharyngeal Dysphagia after anterior cervical spine surgery: a review.
AB  - Study Design Review. Objective Postoperative oropharyngeal dysphagia is one of
      the most common complications following anterior cervical spine surgery (ACSS).
      We review and summarize recent literature in order to provide a general overview
      of clinical signs and symptoms, assessment, incidence and natural history,
      pathophysiology, risk factors, treatment, prevention, and topics for future
      research. Methods A search of English literature regarding dysphagia following
      anterior cervical spine surgery was conducted using PubMed and Google Scholar.
      The search was focused on articles published since the last review on this topic
      was published in 2005. Results Patients who develop dysphagia after ACSS show
      significant alterations in swallowing biomechanics. Patient history, physical
      examination, X-ray, direct or indirect laryngoscopy, and videoradiographic
      swallow evaluation are considered the primary modalities for evaluating
      oropharyngeal dysphagia. There is no universally accepted objective instrument
      for assessing dysphagia after ACSS, but the most widely used instrument is the
      Bazaz Dysphagia Score. Because dysphagia is a subjective sensation, patient
      reported instruments appear to be more clinically relevant and more effective in
      identifying dysfunction. The causes of oropharyngeal dysphagia after ACSS are
      multifactorial, involving neuronal, muscular, and mucosal structures. The
      condition is usually transient, most often beginning in the immediate
      postoperative period but sometimes beginning more than 1 month after surgery. The
      incidence of dysphagia within one week after ACSS varies from 1 to 79% in the
      literature. This wide variance can be attributed to variations in surgical
      techniques, extent of surgery, and size of the implant used, as well as
      variations in definitions and measurements of dysphagia, time intervals of
      postoperative evaluations, and relatively small sample sizes used in published
      studies. The factors most commonly associated with an increased risk of
      oropharyngeal dysphagia after ACSS are: more levels operated, female gender,
      increased operative time, and older age (usually >60 years). Dysphagic patients
      can learn compensatory strategies for the safe and effective passage of bolus
      material. Certain intraoperative and postoperative techniques may decrease the
      incidence and/or severity of oropharyngeal dysphagia after ACSS. Conclusions
      Large, prospective, randomized studies are required to confirm the incidence,
      prevalence, etiology, mechanisms, long-term natural history, and risk factors for
      the development of dysphagia after ACSS, as well as to identify prevention
      measures. Also needed is a universal outcome measurement that is specific,
      reliable and valid, would include global, functional, psychosocial, and physical
      domains, and would facilitate comparisons among studies. Results of these studies
      can lead to improvements in surgical techniques and/or perioperative management,
      and may reduce the incidence of dysphagia after ACSS. 

PMID- 24436883
TI  - Rare infundibular tumors: clinical presentation, imaging findings, and the role
      of endoscopic endonasal surgery in their management.
AB  - Background The spectrum of infundibular lesions is broad and distinct from sellar
      pathologies. In many cases, histology is needed to establish the correct
      diagnosis and determine the treatment approach. Methods Medical files of eight
      patients with distinct infundibular tumors were reviewed. Histopathologically
      confirmed diagnosis included three pituicytomas, three granular cell tumors, and
      two pilocytic astrocytomas. Results Patients shared similar imaging findings and
      clinical symptoms, including visual impairment (n = 5), hypopituitarism (n = 4),
      and headache (n = 4); one patient presented with disseminated disease and
      symptoms from spinal metastases. All the pituicytomas, two granular cell tumors,
      and one infundibular pilocytic astrocytoma case underwent endoscopic endonasal
      surgery; gross total resection was achieved in five patients, three developed
      postoperative diabetes insipidus, and two developed hypopituitarism. No
      recurrences were observed. One granular cell tumor patient was treated with gamma
      knife radiosurgery after stereotactic biopsy; the tumor remained stable in size
      for over 9 years. The infundibular pilocytic astrocytoma patient who presented
      with spinal metastases received radiotherapy and systemic chemotherapy. The
      overall mean follow-up period was 25.1 months. Conclusion Infundibular tumors are
      rare entities that represent a diagnostic challenge. Histopathological
      examination is essential for definitive diagnosis. Surgery, radiation therapy,
      and chemotherapy all have a role in the management of these tumors. 

PMID- 24436884
TI  - Surgical management of endolymphatic sac tumors.
AB  - Objective To review the cumulative experience of surgical management of
      endolymphatic sac tumors (ELSTs) in the literature. To review the experience with
      ELST management at a tertiary referral-based otology-neurotology practice and
      present our approach to management. Study Design Retrospective patient review at
      a referral-based otology-neurotology practice. Methods A review of all available
      records from the House Clinic of patients with ELSTs was performed. Presentation,
      diagnostic workup, microsurgical approach, and outcomes were reviewed. Literature
      review using MEDLINE of studies reporting surgical outcomes of patients with
      ELSTs was also performed. Results Retrospective chart review revealed 18 patients
      with ELSTs who underwent surgical management. Grouping of these patients provides
      surgical outcomes on the largest group of mostly non-von Hippel-Lindau patients
      with ELSTs in the literature. Patients most commonly presented with sensorineural
      hearing loss, tinnitus, and dizziness. A majority of patients presented with
      large tumors exhibiting significant destruction of surrounding structures
      including the cochlea, vestibule, and internal auditory canal. Patients underwent
      microsurgical resection with the intent of complete resection. Conclusions
      Although the extensive nature of ELSTs at time of diagnosis often precludes
      hearing preservation, complete microsurgical resection can be achieved safely
      with preservation of facial function in the majority of cases. 

PMID- 24436886
TI  - Evaluation of variation in the course of the facial nerve, nerve adhesion to
      tumors, and postoperative facial palsy in acoustic neuroma.
AB  - Objective To investigate the variation in the course of the facial nerve (FN) in
      patients undergoing acoustic neuroma (AN) surgery, its adhesion to tumors, and
      the relationship between such adhesions and postoperative facial palsy. Methods
      The subjects were 356 patients who underwent AN surgery in whom the course of the
      FN could be confirmed. Patients were classified into six groups: ventro-central
      surface of the tumor (VCe), ventro-rostral (VR), ventro-caudal (VCa), rostral
      (R), caudal (C), and dorsal (D). Results The FN course was VCe in 185 cases, VR
      in 137, VCa in 19, R in 10, C in 4, and D in one. For tumors < 1.5 cm, VCe was
      most common. For tumors >= 1.5 cm, the proportion of VR increased. No significant
      difference was observed between the course patterns of the FN in terms of
      postoperative FN function, but for tumors > 3.0 cm, there was an increasing
      tendency for the FN to adhere strongly to the tumor capsule, and postoperative
      facial palsy was more severe in patients with stronger adhesions. Conclusions The
      VCe pattern was most common for small tumors. Strong or less strong adhesion to
      the tumor capsule was most strongly associated with postoperative FN palsy. 

PMID- 24436885
TI  - Predictive factors for vision recovery after optic nerve decompression for
      chronic compressive neuropathy: systematic review and meta-analysis.
AB  - Objectives Surgical optic nerve decompression for chronic compressive neuropathy
      results in variable success of vision improvement. We sought to determine the
      effects of various factors using meta-analysis of available literature. Design
      Systematic review of MEDLINE databases for the period 1990 to 2010. Setting
      Academic research center. Participants Studies reporting patients with vision
      loss from chronic compressive neuropathy undergoing surgery. Main outcome
      measures Vision outcome reported by each study. Odds ratios (ORs) and 95%
      confidence intervals (CIs) for predictor variables were calculated. Overall odds
      ratios were then calculated for each factor, adjusting for inter study
      heterogeneity. Results Seventy-six studies were identified. Factors with a
      significant odds of improvement were: less severe vision loss (OR 2.31[95% CI =
      1.76 to 3.04]), no disc atrophy (OR 2.60 [95% CI = 1.17 to 5.81]), smaller size
      (OR 1.82 [95% CI = 1.22 to 2.73]), primary tumor resection (not recurrent) (OR
      3.08 [95% CI = 1.84 to 5.14]), no cavernous sinus extension (OR 1.88 [95% CI =
      1.03 to 3.43]), soft consistency (OR 4.91 [95% CI = 2.27 to 10.63]), presence of
      arachnoid plane (OR 5.60 [95% CI = 2.08 to 15.07]), and more extensive resection
      (OR 0.61 [95% CI = 0.4 to 0.93]). Conclusions Ophthalmologic factors and factors
      directly related to the lesion are most important in determining vision outcome.
      The decision to perform optic nerve decompression for vision loss should be made
      based on careful examination of the patient and realistic discussion regarding
      the probability of improvement. 

PMID- 24436887
TI  - Intraoperative computed tomography guidance to confirm decompression following
      endoscopic endonasal approach for cervicomedullary compression.
AB  - Introduction Cervicomedullary compression often requires an anterior approach to
      address the compressive vector. In certain cases an endoscopic endonasal approach
      (EEA) is ideal for decompression. It is essential that an adequate decompression
      be achieved and verified before the patient leaves the operating room. The
      purpose of this study was to evaluate the use intraoperative computed tomography
      (IO-CT) in assessing the adequacy of decompression. Methods A retrospective chart
      review revealed 11 cases of EEA odontoid resection IO-CT verification of
      decompression. Operative reports and review of imaging was used to determine if
      further decompression was performed following the intraoperative scan. Results
      Out of 11 EEA cases, 4 (36%) patients showed evidence of residual compression
      following an initial IO-CT. Further operative decompression was undertaken
      following the first scan in all cases. A second intraoperative scan was then used
      to confirm complete decompression. No patient left the operating room with
      residual compression. Discussion IO-CT provided valuable utility in 36% of the
      cases after the initial resection was incomplete. The standard fluoroscopic
      guidance may not provide adequate resolution and enhanced utility like IO-CT. 

PMID- 24436888
TI  - Nasopharyngeal branchial cysts-diagnosis and management: a case series.
AB  - Nasopharyngeal branchial cysts (NBCs) have been discussed in the literature in
      only a limited number of publications. Differing from Tornwaldt cysts, NBCs
      present laterally and arise from the fossa of Rosenmuller and may track
      superiorly within the bony confines of the Eustachian tube. Initially patients
      are asymptomatic but may present with aural fullness, unilateral conductive
      hearing loss, and serous otitis media as the cyst mass grows. Two of our three
      patients had the lesion incidentally identified at the time of assessment for
      another diagnosis. In this case series, imaging characteristics and response to
      treatment are reviewed. A literature search was performed to summarize the
      management options for this entity. 

PMID- 24436889
TI  - Lateral temporal bone resection in advanced cutaneous squamous cell carcinoma:
      report of 35 patients.
AB  - Objective To evaluate lateral temporal bone resection (LTBR) in the management of
      advanced cutaneous squamous cell carcinoma (SCC) with temporal bone invasion and
      patterns of failure. Methods This is a retrospective study of 35 patients
      undergoing lateral temporal bone resection for advanced cutaneous SCC at a
      tertiary care center between 1995 and 2006. Results The Pittsburgh tumor stage
      was T4 in 18 patients (51%), T3 in 5 (14%), T2 in 9 (26%), and T1 in 3 (9%).
      Clear margins were reported in 22 (63%) patients. Resection of the mandible
      and/or temporomandibular joint (TMJ) was required in 11 (31%) patients. Facial
      nerve involvement was seen in 10 (29%) patients. Survival outcomes at 2 and 5
      years for overall survival were 72% and 49%; disease-free survival, 68% and 59%;
      and disease-specific survival, 79% and 62%, respectively. Pittsburgh T stage
      correlated significantly with disease-specific survival (p = 0.015) and margin
      status was significant for both disease-free survival (p = 0.0015) and disease
      specific survival (p < 0.001). Conclusions Surgery with curative intent is
      justified for cutaneous SCC invading the temporal bone with extended LTBR. Margin
      status was a significant predictor of outcome. Surgeons should plan
      preoperatively to achieve clear margins by extending the LTBR with possible nerve
      resection. 

PMID- 24436890
TI  - Endoscopic management of cerebrospinal fluid rhinorrhea: the charing cross
      experience.
AB  - Objective To describe our experience of cerebrospinal fluid (CSF) rhinorrhea
      management. Design Retrospective. Setting Charing Cross Hospital, London, a
      tertiary referral center. Participants Fifty-four patients with CSF rhinorrhea
      managed from 2003 to 2011. Main outcome measures Surgical technique; Recurrence.
      Results Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with
      spontaneous and two with traumatic leaks had previous failed repairs in other
      units. Success rates after first and second surgery were 93% and 100%,
      respectively. Mean follow-up was 21 months. Four patients, all of spontaneous
      etiology, had recurrences; three of these underwent successful second repair with
      three layered technique, and the fourth had complete cessation of the leak after
      gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic
      three-layered repair since then averted any further failure in the following 7
      years. Mean body mass index was 34.0 kg/m(2) in spontaneous and 27.8 kg/m(2) in
      traumatic cases (p < 0.05). Fifty percent of spontaneous leaks were from the
      cribriform plate, 22% sphenoid, 14% ethmoid, and 14% frontal sinus. In the
      traumatic CSF leak group: 33.3% were from the cribriform plate, 33.3% sphenoid,
      22.2% ethmoid, and 11.1% frontal. Conclusion Endoscopic CSF fistula closure is a
      safe and effective operation. All sites of leak can be accessed endoscopically.
      We recommend the use of an anatomic three-layered closure in difficult cases. 

PMID- 24436891
TI  - Communicating hydrocephalus and vestibular schwannomas: etiology, treatment, and
      long-term follow-up.
AB  - Background Large vestibular schwannomas (VSs) can cause hydrocephalus by
      obstructing the fourth ventricle. Little is known about the communicating
      hydrocephalus that is seen with a smaller VS. Methods The clinicopathological
      findings and follow up of three patients with communicating hydrocephalus
      associated with a small VS are presented. Results Four patients aged 40 to 66
      years (mean: 57.7) presented with ataxia, dementia, and urinary incontinence. The
      VS were 2.0 to 2.4 cm. The cerebrospinal fluid (CSF) protein was elevated in
      three patients in whom it was measured (1.7 to 6 times normal). The VS was
      resected in two patients. All of the patients required ventriculoperitoneal
      shunting (VPS). All of the patients were asymptomatic or improved at follow-up at
      9 months to 13 years. Conclusion Communicating hydrocephalus associated with a VS
      can occur in younger patients than was previously thought. An elevated CSF
      protein appears to be important, but other factors may be involved. A shunting
      procedure is often required to relieve the symptoms of hydrocephalus even if the
      tumor is resected. Possible etiological causes of communicating hydrocephalus in
      patients with a small VS are discussed. 

PMID- 24436892
TI  - Factors Influencing Decision-making and Outcome in the Surgical Management of
      Trigeminal Neuralgia.
AB  - Objectives The aim was to optimize the algorithm of operative intervention for
      trigeminal neuralgia (TN). Design A multivariate analysis was undertaken to
      determine factors that had influenced both the initial choice of surgical
      intervention and the subsequent outcomes. Setting The study was undertaken with
      patients who underwent microvascular decompression (MVD) or percutaneous glycerol
      injection (PGI) for TN between 2007 and 2009. Participants Seventy-one
      consecutive patients (43 female) were selected. Main Outcome Measures Data were
      prospectively recorded and included demographics, etiology, and presentation of
      TN, duration of symptoms, neurovascular contact, and the outcomes of surgery.
      Results The response rates for MVD and PGI were 96.2% and 87.5%, respectively.
      The recurrence rates were 9.8% following MVD and 33.3% following PGI.
      Multivariate analyses confirmed multiple sclerosis and the identification of
      neurovascular contact as the only factors predictive of the choice of surgical
      intervention and the risk of recurrence following MVD. Conclusions Our approach
      to choosing an operative intervention has been validated. The presence of
      neurovascular contact and the diagnosis of multiple sclerosis influenced the
      choice of surgery and were predictive of subsequent outcome. Both MVD and PGI
      offer effective treatment options for TN. Surgery should be offered early when
      medical management fails. 

PMID- 24436893
TI  - High-resolution computed tomography analysis of variations of the sphenoid sinus.
AB  - Purpose The sphenoid sinus is a complex structure with key variations that are
      important for endoscopic parasellar approaches. In this study, high-resolution
      computed tomography (HRCT) scans were analyzed for the frequency of these
      variations. Methods A retrospective radiographic analysis was conducted on
      patients undergoing HRCT between July 2008 and September 2010. Results Sphenoid
      sinus pneumatization was defined as conchal, presellar, sellar, and postsellar
      based on pneumatization relative to the anterior and posterior face of the sella.
      The distribution ranged from 1.8%, 7.3%, 47.6%, and 43.3%, respectively. We found
      a greater preponderance of sellar and postsellar variation than previously
      reported. No differences were found in regard to age, gender, and ethnicity
      (African American, Caucasian, Asian, and Hispanic) (p > 0.05). The prevalence of
      optic nerve, maxillary nerve, and internal carotid artery protrusion was 26.1%,
      25.9%, and 28.2%, respectively, and dehiscence was 2.1%, 7.4%, and 2.9%,
      respectively. Accessory septae were present in 43.5% of cases. A lateral recess
      was identified in 72.4% and clinoid pneumatization in 20% of patients. Conclusion
      This study demonstrates a greater prevalence of sphenoid sinus pneumatization and
      variations than previously reported. This has important implications in terms of
      preparation and anticipation of possible variations to avoid complications. 

PMID- 24436894
TI  - Morphological Differences between Ruptured and Unruptured Basilar Bifurcation
      Aneurysms.
AB  - Background Aspect ratio (AP), daughter artery ratio (DA), and lateral angle ratio
      (LA) have been reported in middle cerebral artery bifurcation aneurysms to
      correlate with rupture status. Objective To study the differences in AP, DA, LA,
      and aneurysm orientation between ruptured and unruptured basilar bifurcation
      aneurysms. Methods Three-dimensional (3D) angiograms of patients with basilar
      bifurcation aneurysms were analyzed for AP, DA, and LA. Aneurysm projection was
      classified as type A if the long axis of aneurysm was along basilar artery and
      type-B if otherwise. Results Thirty-one ruptured and 17 unruptured aneurysms were
      analyzed. The APs were significantly different (p = 0.008), 2.63 +/- 1.1 for
      ruptured aneurysms and 1.7 +/- 0.55 for unruptured aneurysms. AP >= 1.9
      correlated with rupture status with 68% sensitivity and 70% specificity. Type-A
      configuration was significantly associated with ruptured aneurysms with an odds
      ratio (OR) of 5.9. LAs were 0.9 +/- 0.4 and 1.4 +/- 0.8 for ruptured and
      unruptured aneurysms, respectively, and the difference tended to be significant
      (p = 0.56). DAs were 1.25 +/- 0.22 and 1.21 +/- 0.19 for ruptured and unruptured
      aneurysms without any statistical difference. Conclusion AP > 1.9, type-A
      configuration, and lower LA is associated with ruptured basilar bifurcation
      aneurysms. DA did not differ between ruptured and unruptured aneurysms. 

PMID- 24436895
TI  - The Role of the Pterional Approach in the Surgical Treatment of Olfactory Groove
      Meningiomas: A 20-year Experience.
AB  - Background Olfactory groove meningiomas remain surgically challenging. The common
      microsurgical approaches suffer from late exposure of the neurovascular
      structures. Conversely, the pterional approach has the advantage of early
      dissection of the posterior neurovascular complex. Methods We reviewed the
      records of patients treated for olfactory groove meningioma in our department
      between 1991 and 2010. A total of 61 patients underwent removal of olfactory
      groove meningiomas via the pterional approach. These included 58 primary and 3
      recurrent tumors. Mean overall follow-up time was 122 months. Results Early
      exposure and dissection of the internal carotid artery, middle cerebral artery,
      anterior cerebral artery, and optic nerve was feasible in all cases. Complete
      tumor removal was achieved in 60 patients. Morbidity and mortality rates were 26%
      and 1.6% respectively. Postoperative complications included epileptic seizures
      (five patients) and cerebrospinal fluid (CSF) leak (two patients). During follow
      up, we recorded three tumor recurrences. Conclusions The pterional approach
      appears to be an excellent solution for the treatment of olfactory groove
      meningiomas. Its foremost advantage is early visualization of the posterior
      neurovascular complex. Moreover, it allows frontal sinus preservation and timely
      tumor devascularization and avoids excessive brain retraction. The pterional view
      is familiar to most neurosurgeons and therefore the transition to this technique
      is fairly straightforward. 

PMID- 24436896
TI  - Cerebrospinal Fluid Leakage from Tegmen Tympani Defects Repaired via the Middle
      Cranial Fossa Approach.
AB  - Spontaneous cerebrospinal fluid (CSF) otorrhea due to tegmen tympani defects can
      result in hearing impairment and predispose to meningitis. Seizures or
      neurological deficits are additional risks, particularly when associated with an
      encephalocele. Surgical repair of the dural defect through a middle cranial fossa
      (MCF) approach is a treatment option under these circumstances. This series
      describes eight individuals who presented with CSF otorrhea and MCF
      encephaloceles associated with conductive hearing loss. Defects in the tegmen
      tympani were noted in all patients on preoperative cranial imaging, and six of
      the eight patients had an associated encephalocele. The average age was 57 years
      (range 26 to 67) with a male:female ratio of 7:1. Most defects occurred on the
      left side (6 left/2 right). A standard MCF approach and repair of the dural
      defect with an autologous dural graft (Durepair or DuraGen, Medtronic,
      Minneapolis, Minnesota, USA) and a synthetic polymer glue (DuraSeal, Covidien,
      Mansfield, Massachusetts) was performed in each case with universal success.
      Resolution of the CSF otorrhea was noted in all cases. All cases but one
      exhibited an improvement in hearing. One patient developed a delayed methicillin
      resistant Staphylococcus aureus meningitis 3 months after surgery that resolved
      with surgical re-exploration and antibiotic therapy. Facial nerve monitoring was
      standard. All patients exhibited normal facial function postoperatively.
      Prophylactic lumbar drain placement was only utilized in the first three
      patients. The MCF approach is an excellent route to effectively repair CSF leaks
      and encephaloceles due to tegmen tympani and dural defects. 

PMID- 24436897
TI  - Morphometric analysis of the middle meningeal artery organization in humans
      embryological considerations.
AB  - The middle meningeal artery (MMA) is the largest branch of the internal maxillary
      artery supplying the meninges. The complex sequence of MMA development gives many
      opportunities for variant anatomy. Additionally, the variations in the origin of
      the MMA are of clinical importance when dealing with fractures of the base of the
      skull, epidural hematomas, and bypass procedures. Therefore, various anastomosis
      and aberrant origins of the MMA have been documented in literature. However,
      there are no reports about some morphometric aspects of this important arterial
      segment. Thus, in this study, we decided to investigate the anatomical
      organization of the MMA through the bony groove measurements from human skulls (n
      = 50 subjects). Six measurements were performed bilaterally: angle of the main
      trunk, length of the main trunk, angle between the frontal and parietal branches,
      length of the frontal branch, length of the parietal branch, and length of the
      bony tunnel formed by the frontal branch. We showed that the anatomical
      organization of the MMA is bilaterally similar, except for the length of the
      parietal branch (p = 0.009). Moreover, our results provide baseline normal values
      for future studies aimed at further elucidating the functional and morphological
      pattern of the MMA. 

PMID- 24436898
TI  - What next? The transformation of skull base surgery from a technical procedure to
      a paradigm-based discipline.

PMID- 24436899
TI  - Fully endoscopic resection of pineal region tumors.
AB  - Background and Objective Surgical treatment for pineal tumors is technically
      challenging-weighing the risks and benefits of microsurgical resection for the
      patient with a pineal tumor versus settling for an endoscopic third
      ventriculostomy and biopsy is sometimes difficult. Traditional microsurgical
      resection for pineal region tumors has typically required large open craniotomies
      and involvement or retraction of neural tissue with significant mortality and
      morbidity. With the advancement of high-resolution fiber optics, a fully
      endoscopic, supracerebellar, infratentorial approach, without any cerebellar
      retraction or manipulation of neural tissue, is introduced for the gross total
      resection of pineal region tumors. Conclusion As an endoscopic modification of
      the open craniotomy procedure, this technique combines the advantages and
      benefits of both open microsurgical resection and minimally invasive endoscopic
      surgeries. 

PMID- 24436901
TI  - Endoscopic contralateral superiorly based mucoperiosteal nasal septal flap for
      closure of cerebrospinal fluid leak.
AB  - Objective A novel local contralateral superiorly based mucoperiosteal nasal
      septal flap (CSBMNSF) for closure of a cerebrospinal fluid (CSF) leak from the
      middle anterior base of the skull is described. Materials and Methods A
      retrospective review of patients having endoscopic sinus surgery (ESS) with a CSF
      leak between 2000 and 2009 was performed. The surgical technique is described.
      Two vertical parallel incisions are performed anteriorly and posteriorly in the
      contralateral septal mucosa, joined inferiorly by a horizontal incision.
      Elevation of the flap is completed, leaving it pedicled superiorly. A window is
      created at the highest aspect of the nasal septum to allow transfer of the flap
      to the affected side. Results Four patients with a CSF leak post-ESS for excision
      of a congenital meningocele, tumor removal, and chronic sinusitis are described.
      All were treated successfully using a CSBMNSF. Conclusion A novel, easy-to-handle
      local flap for closure of defects in the anterior middle skull base is described.
      The use of this flap offers less morbidity and less bulkiness compared with other
      local or regional flaps. 

PMID- 24436900
TI  - Adenoid cystic carcinoma of the nasal cavity and paranasal sinuses: a meta
      analysis.
AB  - Objectives To identify independent predictors of outcome in patients with adenoid
      cystic carcinoma (ACC) of the paranasal sinuses and skull base. Design Meta
      analysis of the literature and data from the International ACC Study Group.
      Setting University-affiliated medical center. Participants The study group
      consisted of 520 patients, 99 of them from the international cohort. The median
      follow-up period was 60 months (range, 32 to 100 months). Main Outcome Measures
      Overall survival (OS) and disease-specific survival (DSS). Results The 5-year OS
      and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence
      rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most
      commonly present in the lung, was recorded in 106 patients (29.1%). In the
      international cohort, positive margins and ACC of the sphenoid or ethmoidal
      sinuses were significant predictors of outcome (p < 0.001). Perineural invasion
      and adjuvant treatment (radiotherapy or chemoradiation) were not associated with
      prognosis. Conclusion Tumor margin status and tumor site are associated with
      prognosis in ACC of the paranasal sinuses, whereas perineural invasion is not.
      Adjuvant treatment apparently has no impact on outcome. 

PMID- 24436902
TI  - Modified subtotal lothrop procedure for extended frontal sinus and anterior skull
      base access: a cadaveric feasibility study with clinical correlates.
AB  - Objective The endoscopic modified Lothrop procedure (EMLP) is an established
      approach for recalcitrant frontal sinus disease and anterior skull base exposure.
      However, in select cases, this technique may involve unnecessary resection of
      sinonasal structures. In this study, we propose a modification of the EMLP,
      termed the modified subtotal-Lothrop procedure (MSLP), to access the anterior
      skull base and complex frontal sinus disease for which access to the bilateral
      frontal sinus posterior table is required. Methods A cadaveric dissection with
      photo documentation was performed at an academic medical center on four cadaver
      heads using standard endoscopic techniques to demonstrate the MSLP and its
      feasibility. Results The endoscopic MSLP allowed ample access for instrumentation
      in each of the dissections using a 30- or 70-degree endoscope. Adequate bilateral
      access to the posterior table of the frontal sinus was gained in all cases
      without the need for dissection of the contralateral frontal sinus recess (FSR).
      Conclusion The MSLP appears to be a feasible technique for exposure of the
      anterior skull base and accessing complex frontal sinus pathology. This
      modification provides similar anterior skull base exposure and surgical
      maneuverability as the EMLP while limiting surgical dissection to one FSR,
      thereby preserving as much of the natural mucociliary drainage pathways as
      possible. 

PMID- 24436903
TI  - Antiangiogenic agents for nonmalignant brain tumors.
AB  - Objective To assess the treatment response and side effects for the use of
      antiangiogenic agents such as vascular endothelial growth factor (VEGF)
      inhibitors for patients with vestibular schwannomas and meningiomas. Design and
      Methods Retrospective review of eight male and two female patients (ages 14 to
      70, mean 36 years), treated with bevacizumab (9) or pazopanib (1). Six patients
      had neurofibromatosis type 2 (NF2) with bilateral vestibular schwannomas and
      meningiomas, and the four others had aggressive recurrent meningiomas. Results
      During treatment (range 4 to 21 months, mean 9.1) with antiangiogenic agents, two
      patients with an atypical meningioma and radiation necrosis had dramatic partial
      response, the six NF2 patients had stable or slightly improved disease, and two
      meningioma patients had disease progression. Hearing was stable in three of the
      NF2 patients and was improved in three NF2 patients (one of whom received a
      cochlear implant). Minor toxicities included epistaxis, nausea, diarrhea, weight
      loss, and abdominal pain. No grade 3 or 4 toxicities were observed. Conclusion
      Antiangiogenic agents appear to be safe for the treatment of patients with
      nonmalignant brain tumors, and in select cases may be efficacious. 

PMID- 24436904
TI  - Orbital preservation in patients with esthesioneuroblastoma.
AB  - Objectives Surgical resection in addition to adjuvant radiation with or without
      chemotherapy is the mainstay of treatment for esthesioneuroblastoma (ENB).
      However, management of patients with orbital involvement remains controversial.
      Historically, orbital exenteration has been advocated when there is evidence of
      periorbital invasion. Recently, the indications for orbital exenteration have
      become more selective and orbital preservation has been advocated. We report our
      experience with anterior craniofacial resection and orbital preservation in
      patients with ENB. Design Retrospective review of all patients diagnosed with
      esthesioneuroblastoma who underwent traditional open anterior craniofacial
      resection at the Massachusetts General Hospital/Massachusetts Eye and Ear
      Infirmary Cranial Base Center from 1997 to 2008. Results Sixteen patients were
      identified with a mean follow-up of 76 months. All patients underwent anterior
      craniofacial resection via an open approach and adjuvant proton beam radiation.
      Six of the 16 patients had evidence of either periorbital or lacrimal sac
      involvement at the time of surgery. All of these patients underwent periorbital
      resection to negative histologic margins with preservation of the orbit.
      Conclusion In our study, patients with ENB and periorbital invasion-who were
      treated with anterior craniofacial resection and periorbital resection with
      orbital preservation-had no evidence of decreased survival. In all patients,
      negative histologic margins of the periorbital resection were achieved. 

PMID- 24436905
TI  - Endoscopic endonasal transsphenoidal approach to sellar lesions: a detailed
      account of our mononostril technique.
AB  - Objective The endonasal endoscopic approach is currently under investigation for
      perisellar tumor surgery. A higher resection rate is to be expected and nasal
      complications should be minimized. Here, the authors report their technique of
      transnasal endoscopic neurosurgery after 218 procedures. Methods Between October
      2000 and September 2011, 210 patients received 218 endoscopic endonasal
      transsphenoidal procedures for perisellar lesions. Procedures were video
      recorded. The surgical technique was carefully analyzed. These cases were
      prospectively followed. Results Standard technique was mononostril approach with
      0-degree optics. 30-degree and-after availability-45-degree optics were used for
      assessment of radicality. On follow-up, magnetic resonance imaging revealed
      radical tumor resection in 94 out of 104 cases (90.3%). Recurrent tumor growth
      was observed in five younger patients (2.2%). There was no mortality and a low
      complication rate. Three patients (1.4%) complained postoperatively of nasal
      congestion or reduced nasal air flow; however, no complaints were considered to
      be severe. Conclusion In comparison with other literature reports, the results
      are comparable or even better with respect to surgical radicality. The very low
      rate of nasal complaints is particularly remarkable. The technique has been shown
      to be safe and successful with a high radicality and only minor complications. 

PMID- 24436906
TI  - Acellular dermal allograft for sellar repair after transsphenoidal approach to
      pituitary adenomas.
AB  - Objectives Our practice has transitioned from using fat autograft to acellular
      dermal matrix (AlloDerm, LifeCell Corp, Woodlands, Texas, USA). We present the
      largest series to our knowledge of AlloDerm for sellar floor repair after
      transsphenoidal approach to pituitary adenoma and compare rates of postoperative
      cerebrospinal fluid (CSF) leak with an earlier cohort of patients whose CSF leaks
      were repaired with fat autograft. Design This is a retrospective cohort study
      comparing sellar repair with fat autograft versus inlay Alloderm between the
      years 2003 and 2012. The primary end point was postoperative CSF leak. Results A
      total of 429 patients (368 primary; 83 revision operations) without
      intraoperative lumbar drainage were included. A total of 18 postoperative CSF
      leaks were observed (3.9%). Intraoperative CSF leak occurred in 160 cases
      (35.5%). Among this subset of patients with intraoperative CSF leak, 95 underwent
      repair with AlloDerm and 46 underwent repair with fat autograft, with
      postoperative CSF leak rates of 8.4% and 15.2%, respectively (p = 0.34, chi
      square test); 19 patients underwent repair with other techniques or no repair at
      all, with postoperative leak rate of 0%. Conclusions AlloDerm is an effective
      alternative to fat autograft in cases of low-flow CSF leak following
      transsphenoidal resection of pituitary adenoma. 

PMID- 24436907
TI  - Combined transoral and endoscopic approach for total maxillectomy: a pioneering
      report.
AB  - Total maxillectomy is sometimes necessary especially for malignant tumors
      originating from the maxillary sinus. Here we describe a combined transoral and
      endoscopic approach for total maxillectomy for the treatment of malignant
      maxillary sinus tumors and evaluate its short-term outcome. This approach was
      evaluated in terms of the physiological function, aesthetic outcome, and
      complications. Six patients underwent the above-mentioned approach for resection
      of malignant maxillary sinus tumors from May 2010 to June 2011. This combined
      transoral and endoscopic approach includes five basic steps: total
      sphenoethmoidectomy, sublabial incision, incision of the frontal process of the
      maxilla, incision of the zygomaticomaxillary fissure, and hard palate osteotomy.
      All patients with malignant maxillary sinus tumors successfully underwent the
      planned total endoscopic maxillectomy without the need for facial incision or
      transfixion of the nasal septum; there were no significant complications. Five
      patients received preoperative radiation therapy. All patients were well and had
      no recurrence at follow-up from 13 to 27 months. The combined approach is
      feasible and can be performed in carefully selected patients. The benefit of the
      absence of facial incisions or transfixion of the nasal septum, potential
      improvement in hemostasis, and visual magnification may help to decrease the
      morbidity of traditional open approaches. 

PMID- 24436908
TI  - Patterns of hearing loss following retrosigmoid excision of unilateral vestibular
      schwannoma.
AB  - Objectives To determine the pattern of auditory responses, time-course of hearing
      deterioration, and possible site of lesion following retrosigmoid excision of
      unilateral vestibular schwannomas. Design Prospective, nonrandomized,
      observational pilot study. Setting Tertiary referral medical center. Main outcome
      measures Preoperative and postoperative pure-tone and speech audiometry, auditory
      brainstem response testing, and distortion product otoacoustic emissions were
      performed in 20 patients. Testing was conducted every 24 hours for the duration
      of hospitalization. Transtympanic electrocochleography was performed if delayed
      deterioration of auditory responses was documented. Results Of the 20 patients, 7
      had no discernible cochlear nerve at the end of the procedure. Of the 13 patients
      with an intact nerve, 6 retained hearing, 3 with evidence of reduced neural
      function. Of the 7 who lost hearing despite an intact nerve, 5 lost at least
      cochlear and possibly also neural function, and 1 had reduced neural function but
      retained cochlear function. There were two examples of delayed deterioration of
      cochlear nerve responses. Conclusions Hearing loss following retrosigmoid removal
      of vestibular schwannomas most often involves loss of at least cochlear function,
      possibly in addition to neural damage. In a smaller number of cases anacusis or
      hearing deterioration can be attributed to purely neural trauma. 

PMID- 24436909
TI  - Endonasal access to the upper cervical spine, part one: radiographic morphometric
      analysis.
AB  - Objectives To determine the anatomical relationships that may influence endonasal
      access to the upper cervical spine. Setting We retrospectively analyzed computed
      tomography of 100 patients at a single institution. Participants Participants
      included adults with imaging of the hard palate, clivus, and cervical spine
      without evidence of fracture, severe spondylosis, or previous instrumentation.
      Main Outcome Measures Morphometric analyses of hard palate length and both
      distance and angle between the hard palate and odontoid process were based on
      radiographic measurements. Descriptive zones were assigned to cervical spine
      levels, and endoscopic visualization was simulated with projected lines at 0, 30,
      and 45 degrees from the hard palate to the cervical spine. Results We found an
      inverse relationship between hard palate length and the lowest zone of the
      cervical spine potentially visualized by nasal endoscopy. The distance between
      the posterior tip of the hard palate and the odontoid tip, and the angle formed
      between the two, directly influenced the lowest possible cervical exposure.
      Conclusions Radiographic relationships between hard palate length, distance to
      the odontoid, and the angle formed between the two predict the limits of
      endonasal access to the cervical spine. These results are supported by cadaveric
      data in Part Two of this study. 

PMID- 24436910
TI  - Anterior skull base traumas and their management.

PMID- 24436911
TI  - Johann Christian Rosenmuller (1771-1820): A Historical Perspective on the Man
      behind the Fossa.
AB  - Introduction The fossa of Rosenmuller, also known as the lateral pharyngeal
      recess, is a well-established site of origin of nasopharyngeal carcinoma. It is
      located in the lateral pharyngeal wall behind the cartilaginous portion of the
      Eustachian tube, the torus tubarius, and is named after Johann Christian
      Rosenmuller (JCR). Objective We present a history on the life and extensive works
      of Johann Christian Rosenmuller, a German physician and anatomist. Results Johann
      Christian Rosenmuller was a dedicated anatomist. In addition to identifying the
      fossa of Rosenmuller, his influence extends to various other anatomic subjects,
      including the Rosenmuller gland, the palpebral portion of the lacrimal gland, and
      the organ of Rosenmuller (i.e., the caudal remnant of the mesonephric duct). He
      was also an avid speleologist, studying the composition of caves and their life
      forms. For his contributions to this field, he had a cave in Germany and an
      extinct species named after him-Rosenmullerhohle and Ursus spelaeus Rosenmuller,
      respectively. Conclusion The fossa of Rosenmuller plays an important role in the
      growth and surgical treatment of nasopharyngeal carcinoma. We present a brief
      glimpse into the life of Johann Christian Rosenmuller, for whom it was named. 

PMID- 24436912
TI  - Trends in acoustic neuroma management: a 20-year review of the oxford skull base
      clinic.
AB  - Objective To describe the change in the management of acoustic neuromas at one
      United Kingdom center over a 20-year period and to compare this with what is
      known regarding trends in practice on a national and international scale. Design,
      Setting, and Participants Data was collected prospectively on all patients
      attending the Oxford Skull Base Clinic between 1990 and 2009. Main Outcome
      Measures The proportion of patients managed initially by observation versus
      radiotherapy versus surgery was recorded for each year. Results Significantly
      more patients received radiation treatment (instead of surgery) between 2000 and
      2009 when compared with 1990 to 1999. Compared with national audit data, the
      Oxford Skull Base Clinic treats a higher proportion of patients with radiotherapy
      and significantly lower proportion with surgery, though the trend nationally is
      toward more observation and radiotherapy and less surgery. Conclusion Surgery
      will remain crucial in the management of some patients with acoustic neuromas
      (usually those with the larger tumors where radiosurgery is recognized to be less
      appropriate), but using current trends to predict future practice would suggest
      that alternative nonmicrosurgical treatment may play an increasingly important
      role in the future. 

PMID- 24436913
TI  - Endoscopic resection of tuberculum sellae meningiomas.
AB  - Objective To evaluate the results of endoscopic transnasal resection of
      tuberculum sellae meningiomas (TSMs) as compared with transcranial approaches.
      Design We retrospectively analyzed five patients who underwent endoscopic
      endonasal resection of TSM and performed a comprehensive review of articles
      published between 2000 and 2012 describing the operative treatment of TSMs.
      Results Gross total resection (GTR) was achieved in four patients (80%).
      Transient diabetes insipidus occurred in three patients (60%). Preoperative
      visual field deficit resolved in all patients. Cerebrospinal fluid (CSF) leak
      occurred in one patient. Analysis of published studies included 1,026
      transcranial and 144 transnasal cases. GTR was achieved in 85% of transcranial
      and 72% of transnasal cases. Visual field deficit improved in 65% of transcranial
      and 82% of transnasal cases. Rate of diabetes insipidus and CSF leak was higher
      in the transnasal series. Rate of GTR and visual improvement was higher in
      endoscopic endonasal as compared with microsurgical transnasal series. Conclusion
      The literature supports transsphenoidal surgery for the resection of TSMs with
      significant optic nerve compromise and limited lateral extension. This approach
      may have an equivalent if not superior outcome over transcranial surgery in
      visual outcome. CSF leaks are still a challenge but may improve with the use of
      vascularized nasoseptal flaps. 

PMID- 24436914
TI  - 5-Aminolevulinic Acid and (18)F-FET-PET as Metabolic Imaging Tools for Surgery of
      a Recurrent Skull Base Meningioma.
AB  - Background Metabolic imaging technologies such as 5-aminolevulinic acid (ALA)
      fluorescence-guided resection and positron-emission tomography (PET) imaging have
      improved glioma surgery within the last decade. At present, these tools are not
      routinely used in meningioma surgery. Objective We present a case of a complex
      shaped, recurrent skull base meningioma where 5-ALA fluorescence-guidance and
      (18)F-fluoroethyltyrosine (FET)-PET-imaging facilitated surgical resection.
      Material and Methods The patient underwent surgery via a combined
      transcranial/transnasal endoscopic approach. What was original is that both the
      microscope and the endoscope were equipped for 5-ALA fluorescence-guided surgery,
      respectively. Furthermore, preoperative FET-PET imaging was fused with computed
      tomography (CT) and magnetic resonance imaging (MRI) data for intraoperative
      navigation. The case richly illustrated the performance of the different
      modalities. Conclusions Metabolic imaging tools such as 5-ALA fluorescence-guided
      resection and navigated FET-PET were helpful for the resection of this complex
      shaped, recurrent skull base meningioma. 5-ALA fluorescence was useful to dissect
      the adherent interface between tumor and brain. Furthermore, it helped to
      delineate tumor margins in the nasal cavity. FET-PET improved the assessment of
      bony and dural infiltration. We hypothesize that these imaging technologies may
      reduce recurrence rates through better visualization of tumor tissue that might
      be left unintentionally. This has to be verified in larger, prospective trials. 

PMID- 24436915
TI  - Critical appraisal of extent of resection of clival lesions using the expanded
      endoscopic endonasal approach.
AB  - Objectives To present a critical evaluation of our experience using an expanded
      endoscopic endonasal approach (EEEA) to clival lesions and evaluate, based on the
      location of residual tumor, what the anatomic limitations to the approach are.
      Design A retrospective review of all endoscopic endonasal operations performed at
      our institution identified 19 patients with lesions involving the clivus. Extent
      of resection was determined by preoperative and postoperative tumor volumes.
      Results Three patients underwent planned subtotal resections. Of the remaining
      patients, gross total resection was achieved in 8/16 (50%), > 95% in 5/16 (31%),
      and < 95% in 3/16 (19%). Residual tumor occurred, most commonly with extension
      posterior and lateral to the internal carotid artery, with inferior, lateral
      invasion of the occipital condyle and with deep inferior extension to the
      midportion of the dens. Conclusions The EEEA represents a safe and effective
      technique for the resection of clival lesions. Despite excellent overall
      visualization of this region we found that adequate exposure of the most lateral
      and inferior portions of large tumors is often difficult. Knowledge of these
      limitations allows us to determine which tumors are best suited for an EEEA and
      which may be more appropriate for an open skull base or combined technique. 

PMID- 24436916
TI  - A novel technique for pedicled nasoseptal flap takedown in revision skull base
      surgery.
AB  - Objective To describe a novel technique of using the CO2 laser for a revision
      pedicled nasoseptal flap (PNSF) takedown. Patient Patient with a pituitary
      adenoma recurrence that had undergone an endoscopic skull base resection with a
      nasoseptal flap repair 3 years prior. Procedure Flap edges and bony defect are
      examined using an image-guidance probe to identify the full extent of the defect.
      The CO2 laser fiber is used to incise through to the underlying skull base. The
      flap is then elevated from its most distal portion toward the pedicle, using the
      laser to cut adhesions away from the underlying dura. The skull base defect is
      then repaired with an onlay graft of acellular dermis, then the PNSF. Results The
      laser was adept at dissecting through mucosa to the underlying bone and at
      dissecting the underside of the flap from the posterior adhesions and intradural
      structures safely. Conclusion The novel use of the of the CO2 laser for the flap
      takedown was very effective at safely making the mucosal cuts and dissecting the
      flap from the underlying structures. The nasoseptal flap takedown can be a
      technically challenging procedure that was made easier by the use of the CO2
      laser. 

PMID- 24436917
TI  - Survival and recurrence for patients undergoing surgery of skull base
      intracranial metastases.
AB  - Objective Skull base metastases (SBMs) are rare lesions in close proximity to
      critical neural and vasculature structures. This rarity and complexity have led
      many to only offer nonsurgical therapies. The surgical outcomes for patients with
      SBM therefore remain unknown. Design Retrospective, comparison analyses. Setting
      Johns Hopkins Hospital. Participants All patients who underwent intracranial
      metastatic tumor surgery. Main Outcome Measure Survival and recurrence. Results
      Of the 708 patients who underwent intracranial metastatic tumor surgery, 29 (4%)
      had SBM: 3 (10%) involved the anterior skull base, 7 (24%) the sella, 6 (21%) the
      orbit, 2 (7%) the sphenoid wing, 3 (10%) the clivus, 4 (14%) the petrous bone,
      and 4 (14%) the paranasal sinuses. Following surgery, 6 (50%) had improvements in
      vision and 14 (88%) had improvement and/or maintenance of their cranial nerve
      symptoms. Three (10%), 0(0%), and 1(3%) developed a new motor, language, and
      vision deficit, respectively. There were no differences in median survival (10.0
      versus 9.2 months, p = 0.48) and local progression-free survival (PFS) (p =
      0.52), but there was improved distal PFS (p = 0.04) between patients with and
      without SBM. Conclusions Patients with SBM are relatively rare. These patients
      can tolerate surgery with minimal morbidity and mortality, and they have similar
      prognoses to patients without SBM. 

PMID- 24436918
TI  - Genetic testing in head and neck paraganglioma: who, what, and why?
AB  - Background Genetic testing in head and neck paragangliomas (HNPG) can have
      profound implications in patient and family counseling. Methods Retrospective
      review was performed of patients with HNPG at a cancer care center from 1970 to
      present. Patient demographics, disease patterns, outcomes, and genetic mutations
      were analyzed. Results We identified 26 patients with available genetic testing
      results. Sixteen had mutations. Succinate dehydrogenase gene, sub unit D (SDHD)
      accounted for 75% of mutations, of which P81L accounted for 75%. The remainder
      had SDHB mutations. Patients with mutations were younger (average age 39.5 years
      versus 48.4 years), 63% (versus 40%) had multiple tumors, 94% (60%) had at least
      one carotid body tumor, and family history was positive in 38% (20%). Conclusion
      Patients suspected of heritable HNPG should undergo testing first at the SDHD and
      SDHB loci, and those with younger age, multiple tumors, carotid body tumors, and
      positive family history are more likely to have mutations. 

PMID- 24436919
TI  - Concomitant transsphenoidal approach to the anterior skull base and endoscopic
      sinus surgery in patients with chronic rhinosinusitis.
AB  - Objectives To describe outcomes of endoscopic resection of sellar tumors with
      concomitant endoscopic sinus surgery for patients with chronic rhinosinusitis
      (CRS). Design Retrospective chart review. Setting Tertiary care medical center.
      Participants Patients who underwent endoscopic transsphenoidal surgery for
      excision of anterior skull base lesions and simultaneous functional endoscopic
      sinus surgery (FESS) for CRS between January 2006 and January 2011 by senior
      authors (MRR and JJE). Main Outcomes Measured Short- and long-term postoperative
      complications. Results Fourteen patients were identified. Average follow-up was
      27 months. All patients had preoperative symptoms consistent with CRS. No
      patients were treated with preoperative antibiotics. Surgical pathology revealed
      chronic sinusitis in all specimens. Pathology of the intracranial lesions
      included 11 pituitary macroadenomas, one craniopharyngioma, one chondrosarcoma,
      and one cholesterol granuloma. Short-term postoperative morbidities included a
      sphenoid polyp, one adhesion, and one case of pharyngitis. Long-term outcomes
      included one frontoethmoidal mucocele, one recurrence of nasal polyps, and three
      cases of acute sinusitis. There were no intracranial complications for the entire
      follow-up period. Conclusions Transsphenoidal surgery can safely be performed in
      the setting of CRS without increased risk of intracranial complications. 

PMID- 24436920
TI  - Tuberculum sellae meningiomas: surgical technique, visual outcome, and prognostic
      factors in 51 cases.
AB  - Complete tumor resection with preservation or improvement of visual function is
      the goal of tuberculum sellae meningioma (TSM) treatment. The authors
      retrospectively reviewed 51 patients treated surgically for TSM between 2003 and
      2010, with special attention to surgical technique, visual outcomes, and
      prognostic factors for treatment outcome. All patients were operated via the
      lateral subfrontal approach. The cohort mean age and Karnofsky performance status
      (KPS) on admission was 57.1 +/- 13.6 and 84.3 +/- 11.7, respectively. The most
      common presenting sign was visual impairment. The mean tumor size was 29.4 +/-
      10.7 mm. In 45 of the patients (88.2%), gross total resection was achieved.
      Improvement and/or preservation of visual acuity and visual field were achieved
      in 95.9% and 85.3%, respectively. Visual functions on admission were found to be
      the strongest predictors for postoperative improvement in visual outcome,
      followed by better KPS on admission, smaller tumor size, and young age.
      Postoperative neurological complications included cerebrospinal fluid (CSF) leak,
      meningitis, and postoperative seizures. TSM can be safely operated on through the
      lateral subfrontal approach. A high percentage of complete tumor resection and
      excellent visual outcomes are achieved using this technique. Surgical treatment
      in the early stage of the disease may result in a better visual outcome. 

PMID- 24436921
TI  - De novo development and progression of endolymphatic sac tumour in von hippel
      lindau disease: an observational study and literature review.
AB  - Endolymphatic sac tumors (ELST) are rare invasive lesions of the temporal bone
      that are commonly associated with von Hippel-Lindau disease. This report
      describes serial magnetic resonance imaging (MRI) and computed tomography (CT)
      findings over a period of 6 years in a 12-year-old patient who developed an ELST
      after 3.5 years surveillance for a cerebellar hemangioblastoma. A 1.5 * 8 mm
      tumor was identified on MRI within the endolymphatic duct when the patient
      presented with audiovestibular symptoms due to intralabyrinthine hemorrhage. The
      tumor demonstrated subsequent growth over 25 months until the patient agreed to
      undergo surgical resection by subtotal petrosectomy. De novo development and the
      natural history have been described only in six previous cases. MRI is regarded
      to be unreliable with respect to the ability to demonstrate an ELST in the
      presence of intralabyrinthine hemorrhage, with only two out of four previously
      reported patients demonstrating positive MRI findings. Little is known about the
      precise origin (endolymphatic duct versus sac), growth, and symptom correlation.
      This case highlights that new audiovestibular symptoms are a potential clinical
      clue and intralabyrinthine hemorrhage is a neuroimaging indicator for the
      presence of an ELST, which based on high-resolution MRI appears to originate in
      the endolymphatic duct rather than sac. 

PMID- 24436922
TI  - Transposition of the Pterygopalatine Fossa during Endoscopic Endonasal
      Transpterygoid Approaches.
AB  - Introduction Complete or partial removal of the pterygoid process provides
      lateral extension of the endonasal corridor necessary to approach the Meckel
      cave, infrapetrous skull base, and medial infratemporal fossa. This paper
      provides the anatomical foundations for the endoscopic endonasal transpterygoid
      approach with preservation of all neurovascular structures inside the
      pterygopalatine fossa. Methods Eight endoscopic transpterygoid approaches were
      performed in fresh cadaveric specimens. In all dissections the vidian nerve and
      the periosteal sac enclosing the pterygopalatine fossa were preserved. Results We
      reliably transposed the pterygopalatine fossa to approach the Meckel cave,
      infrapetrous skull base, and medial infratemporal region, preserving the
      neurovascular structures inside the pterygopalatine fossa in all specimens.
      Conclusions The transposition of the pterygopalatine fossa neurovascular
      structures for endoscopic endonasal approaches to the skull base is an
      alternative technique that is both feasible and desirable. The transposition
      requires no additional technical skills but requires comprehensive knowledge of
      its anatomy. The anatomical preservation of the neurovascular structures is
      potentially beneficial to the quality of life of patients. Clinical studies are
      necessary to prove the real benefits of this technique. 

PMID- 24436923
TI  - Focus on the Lateral Incisural Space: Where is the Trochlear Nerve?
AB  - Objective To define the entrance point of the trochlear nerve in the free edge of
      the tentorium, giving a topographical description in relation to supratentorial
      and infratentorial reference points. Method The study was performed on seven
      formaldehyde-fixed specimens (14 sides). The distance from supratentorial and
      infratentorial reference points to the entrance point of the trochlear nerve into
      the free tentorial edge was measured. Results The cisternal segment of the
      trochlear nerve, the tentorial entry point, and the reference points could be
      clearly identified in all specimens. The assessed distances measured from the
      tentorial entry point of the trochlear nerve to the anterior clinoid process was
      14 to 28 mm, to the posterior clinoid process was 9 to 19 mm, to the posterior
      lip of the inner auditory canal was 25 to 29 mm, to the posterior border of the
      Meckel cave was 9 to 14 mm, and to the oculomotor triangle was 5 to 16 mm.
      Conclusions The cisternal length of the trochlear nerve shows a marked
      variability and may be further distorted by tumors, whereas the entry point into
      the tentorium is a stable landmark. Therefore, it might be an important reference
      point for identifying the nerve before cutting the tentorium. 

PMID- 24436924
TI  - Interaural Difference of Wave V Predicting Postoperative Hearing in Gardner
      Robertson Class II Acoustic Neuroma Patients.
AB  - Patients with acoustic neuroma classified in Gardner and Robertson (GR) Class II
      should be considered to have useful hearing, and patients classified in Class III
      should be considered to have not-useful hearing. Therefore, it is important for
      acoustic neuroma surgery to distinguish between postoperative GR Class II and
      Class III patients by brainstem auditory evoked potentials (BAEPs). We evaluate
      which BAEP parameter is the best for predicting postoperative GR Class II or III
      in 36 preoperative GR Class II patients with unilateral acoustic neuroma. Delay
      in wave V latency, reduction ratio in wave V amplitude, and interaural difference
      of wave V (IT5) are evaluated by a receiver-operating characteristic (ROC) curve
      in this study. IT5 is the best distinguishing parameter between postoperative
      Class II and Class III. IT5 below 1.12 millisecond (msec) should be a good marker
      to preserve postoperative useful hearing. Thus, comparing the latency of wave V
      on both sides is important, and surgeons would be able to make more informed
      decisions during surgery by checking IT5 on BAEPs. 

PMID- 24436925
TI  - Restoration of the orbital aesthetic subunit with the thoracodorsal artery system
      of flaps in patients undergoing radiation therapy.
AB  - Objectives To demonstrate the advantages of the thoracodorsal artery scapular tip
      autogenous transplant (Tdast) for patients requiring restoration of the orbital
      aesthetic subunit. Design Prospective case series. Setting Tertiary center.
      Participants Ten patients (M:F,6:4) with a mean age of 56 years (range, 21 to 78
      years) underwent restoration of the orbital aesthetic subunit and radiation
      therapy between 2001 and 2008. Main Outcome Measures The two reconstructive
      advantages of the thoracodorsal artery system of flaps for orbital reconstruction
      are a long pedicle and the suitability of the scapula tip to meet the three
      dimensional requirements of the orbit. Patients were assessed 1 year or more
      after treatment for cosmetic outcome, work status, and socialization. Results
      Eight of 10 patients benefited from the three-dimensional nature of the scapula
      tip bone and 7 of 10 avoided vein grafting. Four of five evaluable patients
      reported "frequently" socializing outside their home. Four of five evaluable
      patients working before undergoing their treatment were able to return to work
      posttreatment. Seven of nine patients with postoperative photographs had minimal
      or no facial contour deformity. Conclusions The Tdast can restore orbital contour
      without osteotomy, and the thoracodorsal artery system of flaps has a long
      vascular pedicle that reduces vein grafting. Patients have an acceptable cosmetic
      result and return to preoperative work status and socialization. 

PMID- 24436926
TI  - Chicken wing training model for endoscopic microsurgery.
AB  - Objectives To present and validate a chicken wing model for endoscopic endonasal
      microsurgical skill development. Setting A surgical environment was constructed
      using a Styrofoam box and measurements from radiological studies. Endoscopic
      visualization and instrumentation were utilized in a manner to mimic operative
      setting. Design Five participants were instructed to complete four sequential
      tasks: (1) opening the skin, (2) exposing the main artery in its neurovascular
      sheath, (3) opening the neurovascular sheath, and (4) separating the nerve from
      the artery. Time to completion of each task was recorded. Participants Three
      junior attendings, one senior resident, and one medical student were recruited
      internally. Main Outcome Measures Time to perform the surgical tasks measured in
      seconds. Results The average time of the first training session was 48.8 minutes;
      by the 10th training session, the average time was 22.4 minutes. The range of
      improvement was 25.7 minutes to 72.4 minutes. All five participants exhibited
      statistically significant decrease in time after 10 trials. Kaplan-Meier analysis
      revealed that an improvement of 50% was achieved by an average of five attempts
      at the 95% confidence interval. Conclusions The ex vivo chicken wing model is an
      inexpensive and relatively realistic model to train endoscopic dissection using
      microsurgical techniques. 

PMID- 24436927
TI  - Metastatic disease to the clivus mimicking clival chordomas.
AB  - Objectives/Hypothesis A comprehensive review of the literature of clival
      metastases and presentation of two additional cases. Study Design Literature
      review and report of two cases. Methods A literature review of the MEDLINE
      database (1950 to January 19, 2013) was performed to identify all cases of
      patients with metastatic disease to the clivus. Additionally, two novel cases are
      presented. Results In total, 47 cases were identified in the literature,
      including the two cases presented in this study. Metastatic disease to the clivus
      is the initial presenting symptom of the primary malignancy in 36% (13/36) of the
      cases. When there was a history of malignancy, the median interval of time to
      clival metastases was 24 months (range 1 to 172 months). Clinical symptoms
      manifested often as cranial neuropathies, with at least abducens palsies as the
      initial presenting symptom in 61.9% (26/42) of patients. Tumor pathology was
      diverse, but several pathologies were seen more commonly: prostate carcinoma
      (18.1%, 9/47), hepatocellular carcinoma (10.6%, 5/47), and thyroid follicular
      carcinoma (8.5%, 4/47). Conclusion Although clival metastases are extremely rare,
      they are an important part of the differential of clival masses as they can be
      the presenting symptom of distant malignancy. Level of Evidence 4. 

PMID- 24436928
TI  - Quantitative comparison of retrosigmoid intradural suprameatal approach and
      retrosigmoid transtentorial approach: implications for tumors in the petroclival
      region.
AB  - Background Retrosigmoid transtentorial (RTT) and retrosigmoid intradural
      suprameatal (RISA) approaches have been used in the treatment of petroclival
      tumors. Objective To compare the area of exposure of brainstem and petroclival
      region obtained through RTT and RISA in cadaveric specimens. Methods Five
      cadaveric specimens with a total of 10 sides were analyzed. RTT and RISA were
      performed on five sides each. Brainstem and petroclival surface exposure were
      measured using both the approaches. These values were compared between the two
      approaches. Results Brainstem area exposure with RTT was 441 +/- 63 mm(2) and
      that with RISA was 311 +/- 61 mm(2). Student's t-test revealed that the
      difference was significant (p = 0.01). The area of petroclival exposure medial to
      the Meckel cave through RTT was 696 +/- 57 mm(2), and that through RISA was 716
      +/- 51 mm(2) (p = 0.69). The area of brainstem exposure between V and VII-VII
      complex through RTT and RISA was 387 +/- 86 mm(2) and 378 +/- 76 mm(2) (p =
      0.87). Conclusion The RTT approach is an excellent approach to ventrolateral
      brainstem and petroclival region. It provides greater superoventral exposure of
      the ventrolateral brainstem than RISA and provides similar petroclival exposure. 

PMID- 24436929
TI  - One-piece modified gasket seal technique.
AB  - Objectives Review the effectiveness of a modified gasket seal technique utilizing
      a porous high-density polyethylene plate/rectus sheath fascia construct without
      fat grafting for primary closure of anterior defects following endoscopic skull
      base surgery. Design Retrospective review (2011-2012). Setting Single academic
      medical center. Methods A retrospective review of five patients who underwent
      expanded endoscopic endonasal surgery for various pathologies (two
      craniopharyngiomas, two tuberculum meningiomas, and one planum meningioma) was
      performed. Skull base closure was performed using a one-piece modified gasket
      seal technique. Primary outcome measures included postoperative cerebrospinal
      fluid (CSF) leaks and donor site morbidity. Results There were no postoperative
      CSF leaks. Two patients experienced aseptic meningitis treated with a 14-day
      course of steroids. Two patients experienced new postoperative chronic/recurrent
      sinusitis treated with oral antibiotics and topical nasal therapy. There was no
      donor site morbidity such as infection, hematoma, or hernias. Conclusions The one
      piece modified gasket-seal closure is a safe and effective method for
      reconstruction of endonasal defects of the anterior skull base. Rectus sheath
      fascia is an appropriate dural substitute for free tissue grafting with low donor
      site morbidity. The construction of the one-piece graft significantly decreases
      operative time and lowers the learning curve for multilayered closure. 

PMID- 24436930
TI  - The Use of the Temporoparietal Fascial Flap in Preventing CSF Leak after Lateral
      Skull Base Surgery.
AB  - Objective Determine the effectiveness of the temporoparietal fascia flap (TPFF)
      with adipose tissue in preventing cerebrospinal fluid (CSF) leaks for lateral
      skull base tumor reconstruction. Design A retrospective chart review from 2005 to
      2010 was conducted of patients undergoing skull base tumor resection. Patients
      with TPFF reconstruction were compared with those with adipose packing alone
      based on lumbar drain placement, tumor size, extent of dissection, and incidence
      of CSF leak. Data was analyzed with a Fisher exact test at p < 0.05. Setting
      Tertiary care institution. Main Outcome Measures Incidence of CSF leak. Results A
      total of 16 patients had a TPFF reconstruction; 20 had adipose only. Four TPFF
      patients had lumbar drain placement, as did six in the adipose-only group. Six
      patients had a CSF leak, all in the adipose-only group (p = 0.02). Patients with
      a lumbar drain were more likely to have larger tumors (p = 0.01) and to have a
      CSF leak if they had adipose-only reconstruction (p = 0.07). Conclusions Lateral
      skull base reconstruction using TPFF with adipose tissue is easily performed and
      has a low operative morbidity. Early results show a significant decrease in the
      rate of CSF leak using TPFF, particularly in high-risk patients. 

PMID- 24436931
TI  - Radiological and Clinical Factors Predicting the Facial Nerve Outcome following
      Retrosigmoid Approach for Large Vestibular Schwannomas (VSs).
AB  - Objective The aim of our study was to identify the radiological and clinical
      factors that predict postoperative facial nerve outcome following retrosigmoid
      approach for large vestibular schwannomas (VSs). Methods A total of 72 patients
      with large (>= 3 cm) vestibular schwannomas was included in this retrospective
      study. Various parameters evaluated were age, gender, clinical presentation,
      tumor diameter in three planes, intrameatal extension, and pattern of growth.
      Results Age of the patient and presenting symptoms such as headache, ataxia, or
      preoperative facial nerve dysfunction correlated with poorer facial nerve outcome
      (p < 0.05). Patients with larger tumor volumes and extrameatal growth experienced
      a worse outcome (p < 0.05). Anterior and caudal extension (p = 0.001) correlated
      with poorer outcome, as well. Intrameatal extension and bony changes of the
      internal acoustic meatus did not correlate with the outcome (p > 0.05). Of the
      various examined factors, preoperative facial nerve function independently
      predicted postoperative facial nerve outcome. Conclusion Our study suggests that
      young patients with small tumor volume and normal facial nerve function at
      presentation are more likely to experience a good postoperative facial nerve
      outcome. These clinical and radiological parameters can be used to predict facial
      nerve outcome prior to surgery. 

PMID- 24436932
TI  - Outcomes following Microvascular Free Tissue Transfer in Reconstructing Skull
      Base Defects.
AB  - Objective Successful resection of complex tumors involving the skull base (SB)
      depends on the ability to reconstruct the resulting defects. The objective of
      this study was to assess the outcomes of patients undergoing reconstruction after
      resection of SB tumors with free flaps. Methods From 1995 to 2010 a retrospective
      review of cases was undertaken. Demographics, histology, surgical management,
      complications, locoregional control, and survival were analyzed. Results We
      performed 62 flaps in 57 patients. There was a preponderance of sinonasal
      malignancies (45%), and most lesions involved the anterior SB (81%). A total of
      94% of patients underwent radiotherapy. Reconstruction was undertaken mainly with
      anterolateral thigh (37%) or radial forearm (34%) flaps. Complications occurred
      in 17% of patients, and the flap's success rate was 94%. Conclusion Free flaps
      are versatile and highly reliable for reconstructing defects resulting from
      resections of the SB. They should be considered for SB reconstruction of large
      three-dimensional defects as well as defects involving an irradiated field.
      Successful reconstruction of the SB can be performed using a small number of
      highly dependable flaps. 

PMID- 24436933
TI  - What is the Best Route to the Meckel Cave? Anatomical Comparison between the
      Endoscopic Endonasal Approach and a Lateral Approach.
AB  - Background Traditionally, a pterional approach is utilized to access the Meckel
      cave. Depending on the tumor location, extradural dissection of the Gasserian
      ganglion can be performed. An endoscopic endonasal access could potentially avoid
      a craniotomy in these cases. Methods We performed an endoscopic endonasal
      approach as well as a lateral approach to the Meckel cave on six anatomic
      specimens. To access the Meckel cave endoscopically, a complete
      sphenoethmoidectomy and maxillary antrostomy followed by a transpterygoid
      approach was performed. For lateral access, a pterional craniotomy with
      extradural dissection was performed. Results The endoscopic endonasal approach
      allowed adequate access to the Gasserian ganglion. All the relevant anatomy was
      identified without difficulty. Both approaches allowed for a similar exposure,
      but the endonasal approach avoided brain retraction and improved anteromedial
      exposure of the Gasserian ganglion. The lateral approach provided improved access
      posterolaterally and to the superior portion. Conclusion The endoscopic endonasal
      approach to the Meckel cave is anatomically feasible. The morbidity associated
      with brain retraction from the open approaches can be avoided. Further
      understanding of the endoscopic anatomy within this region can facilitate
      continued advancement in endoscopic endonasal surgery and improvement in the
      safety and efficacy of these procedures. 

PMID- 24436934
TI  - Forces Applied at the Skull Base during Transnasal Endoscopic Transsphenoidal
      Pituitary Tumor Excision.
AB  - Objectives Our laboratory is developing a surgical robotic system to further
      improve dexterity and visualization that will allow for broader application of
      transnasal skull base surgery. To optimize this system, intraoperative force data
      are required. Using a modified curette, force data were recorded and analyzed
      during pituitary tumor excision. Design A neurosurgical curette was modified by
      the addition of a force sensor. The instrument was validated in an in vitro model
      to measure forces during simulated pituitary tumor excision. Following this,
      intraoperative force data from three patients during transnasal endoscopic
      excision of pituitary tumors was obtained. Setting Academic medical center. Main
      Outcome Measures Forces applied at the skull base during surgical excision of
      pituitary tumors. Results Average forces applied during in vitro testing ranged
      from 0.1 to 0.15 N. Average forces recorded during in vivo testing ranged from
      0.1 to 0.5 N. Maximal forces occurred with collisions of the bony sella. The
      average maximal force was 1.61 N. There were no complications related to the use
      of the modified curette. Conclusions Forces to remove pituitary tumor are small
      and are similar between patients. The in vitro model presented here is adequate
      for further testing of a robotic skull base surgery system. 

PMID- 24436935
TI  - Image-guided percutaneous aspiration and gelfoam treatment of petrous apex
      cholesterol granuloma: a new theory and method for diagnosis and treatment.
AB  - Although diagnosis of cholesterol granulomas of the skull base can be
      straightforward with computed tomography (CT) and magnetic resonance imaging
      (MRI) appearance, treatment is controversial with various skull base approaches
      described in the literature. This report describes a 35-year-old man who
      presented with a symptomatic, enlarging cystic lesion in the left petrous apex
      and clivus that had imaging features of a cholesterol granuloma (cholesterol
      cyst). Due to a prior history of treated mediastinal germ cell tumor, pathologic
      confirmation of the lesion was requested. A CT-guided percutaneous aspiration
      revealed dark used motor oil-like fluid. Continued aspiration yielded a change in
      the character of the fluid to marrow red. Injection of contrast revealed no
      communication with cerebrospinal fluid. Gelfoam (Pfizer, New York, New York, USA)
      was subsequently injected percutaneously into the residual cavity. Histopathology
      showed no evidence of malignancy and follow-up MRI at 1 month, 3 months, 6
      months, and 1 year demonstrated continued decrease in size and signal of the
      lesion. 

PMID- 24436936
TI  - Use of preoperative MRI to predict vestibular schwannoma intraoperative
      consistency and facial nerve outcome.
AB  - Objectives We sought to identify if preoperative schwannoma magnetic resonance
      imaging (MRI) intensities might predict intraoperative consistency. We then
      determined whether consistency correlated with facial nerve outcomes. Design
      Operative reports from 2000 to 2010 were searched for tumor description as either
      soft and/or suckable or firm and/or fibrous. Preoperative T1 and T2 sequences
      were then reviewed to identify intensities relative to gray matter. Facial nerve
      function was recorded at the time of most recent follow-up. Results Forty-six
      patients were included. No tumors were T1 hyperintense. Soft and firm schwannomas
      were equally likely to be T1 hypointense. On T2 sequences, however, soft
      schwannomas were more likely to be hyperintense (88% versus 14%, p < 0.005)
      whereas firm schwannomas were more likely to be hypointense (86% versus 6%, p <
      0.005). There was a tendency for firm schwannomas to have worse facial nerve
      outcomes (43% versus 19%, p = 0.14). Conclusions Prediction of vestibular
      schwannoma intraoperative consistency based on T2 intensity seems promising.
      Furthermore, though not statistically significant, in this small pilot study firm
      schwannomas tended to have worse facial nerve outcomes. This potential ability to
      predict consistency and its correlation with facial nerve outcome may assist the
      surgeon in preoperative planning and patient counseling, though further data
      needs to be accumulated. 

PMID- 24436937
TI  - Radiologic assessment of the paranasal sinuses after endoscopic skull base
      surgery.
AB  - Objectives To identify sinuses demonstrating postoperative radiographic mucosal
      thickening after endoscopic exposure of the cranial base through the
      transsphenoidal corridor. Design Retrospective review. Setting University-based
      medical center. Participants Patients undergoing endoscopic transnasal
      transsphenoidal approaches to the skull base who had both preoperative and
      postoperative imaging. Main Outcome Measures Change in preoperative and
      postoperative imaging scores for each sinus and side at 3 and 6 months. The left
      sided undissected sinuses served as internal controls for comparison. Results
      Fifty-one patients were identified with the aforementioned inclusion and
      exclusion criteria. The mean difference in preoperative and postoperative imaging
      scores for the right anterior ethmoid sinus was significantly different from the
      left-sided equivalents (p = 0.0020). The difference in the frontal sinuses
      approached significance (p = 0.0625). Conclusions Resection of the lower half of
      the middle turbinate and maxillary antrostomy and harvest of a nasoseptal flap
      are associated with an increased radiographic incidence of mucosal thickening of
      the ipsilateral anterior ethmoids compared with the undissected contralateral
      side. When accessing the transnasal transsphenoidal corridor for skull base
      surgery, preservation of native anatomy is associated with a lower incidence of
      mucosal thickening on postoperative imaging. 

PMID- 24436938
TI  - Application of Novel CO2 Laser-Suction Device.
AB  - Background Development of the flexible CO2 fiber has presented new opportunities
      for the use of precision laser cutting in cranial procedures. The efficacy of the
      CO2 scalpel is further enhanced by combining it with a fluid removal suction
      capability. Objectives We report our experience with a novel CO2 laser-suction
      device. Methods The novel laser-suction device was designed in conjunction with
      OmniGuide Inc. (Cambridge, Massachusetts, USA). We performed a case review of its
      use in firm tumors that were resistant to resection by bipolar, suction, and
      ultrasonic aspirator. Results The laser-suction device was applied in three
      tumors where resection with ultrasonic aspiration failed. Tumor resection using
      the laser-suction device was successful in all three cases. There were no
      complications related to the laser-suction device. There were no instances of
      intraoperative device malfunction. Discussion The CO2 laser combined with suction
      is a useful instrument for resection of firm tumors that prove to be resistant to
      ultrasonic aspiration. We also find it to be useful in settings where precise
      tissue incisions are desired with minimal manipulation. In our experience, the
      surgical efficiency of the CO2 laser is improved by the laser-suction device.
      This device allows the surgeon to utilize a suction device and laser in a single
      hand and enables concurrent use of bipolar electrocautery without repeated
      instrument changes. 

PMID- 24436939
TI  - Fibrous dysplasia of the maxilla: diagnostic reliability of the study image.
      Literature review.
AB  - Objective Fibrous dysplasia (FD) is a benign bone disorder in facial bones. This
      study evaluates the possibility of diagnosing fibrous dysplasia on imaging alone,
      without biopsy of the lesion, which is often burdensome for the patient.
      Materials and Methods The authors bring their experience of four cases of bone
      lesions of the maxillofacial region and present a review of published studies.
      The imaging techniques evaluated are computed tomography (CT) and magnetic
      resonance imaging (MRI) with and without contrast. Results The literature review
      demonstrates that it is impossible to make diagnosis of fibrous dysplasia
      exclusively by imaging. Radiographic images often show a ground-glass appearance,
      which is characteristic but not pathognomonic of fibrous dysplasia. Conclusion
      Although CT and MRI images may in many cases suggest a diagnosis of fibrous
      dysplasia, histological examination or follow-up imaging should follow. 

PMID- 24436940
TI  - The extended nasoseptal flap for skull base reconstruction of the clival region:
      an anatomical and radiological study.
AB  - Objective Reconstruction of large clival defects after an endoscopic endonasal
      procedure is challenging. The objective is to analyze the morphology,
      indications, and limitations of the extended nasoseptal flap, which adds the
      nasal floor and inferior meatus mucosa, compared with the standard nasoseptal
      flap, for clival reconstruction. Design Twenty-seven sides of formalin-fixed
      anatomical specimens and 13 computed tomography (CT) scans were used. Under 0
      degree endoscopic visualization, a standard flap on one side and an extended flap
      on the other side were performed, as well as exposure of the sella, cavernous
      sinus, and clival dura mater. Coverage of both flaps was assessed, and they were
      incised and extracted for measurements. Results The extended flap has two parts:
      septal and inferior meatal. The extended flaps are 20 mm longer and add 774 mm(2)
      of mucosal area. They cover a clival defect from tuberculum to foramen magnum in
      66.6% cases and from below the sella in 91.6%. They cover both parasellar and
      paraclival segments of the internal carotid arteries. The lateral inferior limits
      are the medial aspect of the hypoglossal canals and Eustachian tubes. CT scans
      can predict the need or limitation of an extended nasoseptal flap. Conclusions
      The nasal floor and inferior meatus mucosa adds a significant area for
      reconstruction of the clivus. A defect laterally beyond the hypoglossal canals is
      not likely covered with this variation of the flap. Preoperative CT scans are
      useful to guide the reconstruction techniques. 

PMID- 24436941
TI  - Endoscopic endonasal transplanum approach to the paraclinoid internal carotid
      artery.
AB  - Objective To investigate the relevance of an endoscopic transnasal approach to
      the surgical treatment of paraophthalmic aneurysms. Setting Binasal endoscopic
      transplanum surgery was performed. Participants Seven cadaver heads were studied.
      Main Outcome Measures (1) Dimensions of the endonasal corridor, including the
      operative field depth, lateral limits, and the transplanum craniotomy. (2) The
      degree of vascular exposure. (3) Surgical maneuverability and access for clip
      placements. Results The mean operative depth was 90 +/- 4 mm. The lateral
      corridors were limited proximally by the alar rim openings (29 +/- 4 mm) and
      distally by the distance between the opticocarotid recesses (19 +/- 2 mm). The
      mean posteroanterior distance and width of the transplanum craniotomy were 19 +/-
      2 mm and 17 +/- 3 mm, respectively. Vascular exposure was achieved in 100% of
      cases for the clinoidal internal carotid artery (ICA), ophthalmic artery,
      superior hypophyseal artery, and the proximal ophthalmic ICA. Surgical access and
      clip placement was achieved in 97.6% of cases for vessels located anterior to the
      pituitary stalk (odds ratio [OR] 73.8; 95% confidence interval [CI] 7.66 to
      710.8; p = 0.00). Conclusion The endoscopic transnasal approach provides
      excellent visualization of the paraclinoid region vasculature and offers
      potential surgical alternative for paraclinoid aneurysms. 

PMID- 24436942
TI  - Endoscopic endonasal approach to the infraorbital nerve with nasolacrimal duct
      preservation.
AB  - Objectives Infraorbital nerve (ION) decompression, excision to remove intrinsic
      tumors, and resection with oncological margins in malignancies with perineural
      invasion or dissemination are usually accomplished with an open approach. The
      objective is to describe the surgical anatomy, technique, and indications of the
      endonasal endoscopic approach (EEA) to the ION with nasolacrimal duct
      preservation. Design Eleven sides of formalin-fixed specimens were dissected. An
      anterior maxillary antrostomy was performed. The length of the ION prominence
      within the sinus and anatomic features of the covering bone were studied. A 45
      degree endoscope visualized the infraorbital prominence endonasally. An angled
      dissector and dural blade allowed for dissection and resection of the ION
      ipsilaterally and contralaterally. Results The bone features of the ION
      prominence allowed for ipsilateral dissection in 10 out of 11 sides. In one case
      with the ION surrounded by thick cortical bone, the dissection could only be
      started by drilling contralaterally. The 45-degree endoscope visualized 92.2% and
      100% of the length of the nerve using the ipsilateral and contralateral nostrils,
      respectively. Ipsilaterally, 83% of its length was resected, and 96.3% was
      resected contralaterally. Conclusion The ION can be approached using an
      ipsilateral EEA with nasolacrimal duct preservation in most cases. The
      contralateral approach provides a wider angle to access the ION. This technique
      is primarily indicated in cases where the EEA can be used for tumor resection and
      oncological margins within the ION. 

PMID- 24436943
TI  - Successful management of a catecholamine-secreting glomus jugulare tumor with
      radiosurgery alone.
AB  - Secretory glomus jugulare tumors are often resected surgically to control the
      systemic effects of the catecholamines they produce. This involves complex skull
      base surgery, which carries significant risks and frequent morbidity.
      Stereotactic radiosurgery (SRS) is a recently recognized treatment for glomus
      jugulare tumors, though little is known about its use in secretory tumors. Case
      Report A young fit patient with a catecholamine-secreting glomus jugulare tumor
      was treated with SRS alone and over the following 37 months her urinary
      catecholamine excretion fell to near normal levels, and serial magnetic resonance
      imaging (MRI) confirmed a reduction in tumor volume. Discussion Radiosurgery is
      an accepted treatment for glomus jugulare tumors and is now readily available to
      skull base surgeons. In this case a catecholamine-secreting tumor was
      successfully controlled with radiosurgery alone. Further research and long-term
      follow-up will determine the role of this treatment in the nonsurgical management
      of secreting glomus jugulare tumors. 

PMID- 24436944
TI  - Diagnostic/genetic sreening - approach for genetic diagnoses and prevention of
      cleft lip and/or palate.
AB  - The treatment, research and volunteer work for cleft lip and/or palate (CL/P) has
      been led for over 30 years by our team. Within this period, more than 4,000 cases
      of CL/P were treated and at the same time, and approximately 400 papers were
      published as the first or partner researcher in Nature Genetics, New England
      Journal of Medicine and others. In addition, with $20 million that was donated
      from companies and laypeople, and the grant from the Japanese government, CL/P
      centres in many countries and in Japan, the oral and craniofacial congenital
      anomaly gene bank in our CL/P centre was established by our leadership. In the
      bank there are genes from approximately more than 8,000 cases. The genes were
      mapped with Professor Jeffery Murray of Iowa University in the United States, the
      findings about genetic syndromes such as Van der Woude Syndrome and basal cell
      nevus syndrome were applied in clinical settings. The genetic counselling section
      that specialises in the oral and maxillofacial field was established by our
      effort for the first time in Japan. In this review, our clinical experience and
      approach for genetic diagnoses and prevention of cleft lip and/or palate will be
      discussed. 

PMID- 24436945
TI  - Variation in mesiodistal root angulation of panoramic images generated from cone
      beam computed tomography.
AB  - OBJECTIVE: To compare the mesiodistal root angulation of panoramic images
      generated from traditional panoramic tomography or cone-beam computed tomography
      (CBCT). METHODS: CBCT scans and panoramic radiographs of 20 patients were
      collected. The Invivo- Dental 5.0 was separately applied for maxillary or
      mandibular panoramic image generation. The generation method was assorted by two
      head positions, the Frankfort plane horizontal position (P1) and the occlusal
      plane horizontal position (P2), and three central plane settings (root apical
      plane, tooth centre plane and crown marginal plane). The amount of mesiodistal
      root angulation on panoramic images generated from CBCT (GPIs) deviated from that
      on the traditional panoramic images was calculated by paired sample test. The
      variation trends were explored with different head rotation and incisors'
      buccolingual root inclination. RESULTS: By selecting the tooth centre plane, the
      GPIs were suggested to be generated by the Frankfort plane horizontal position
      for maxilla; while the occlusal plane horizontal position was advised for
      mandibular GPIs' generation. Moreover, the mesiodistal root angulations were
      demonstrated to regularly change along with variations of head rotation and the
      incisors' buccolingual root inclination. CONCLUSION: Panoramic images can be
      generated from CBCT by the standard operating procedures with proper head
      position and central plane setting. But cautions should be taken during the
      generation, bearing the variability of mesiodistal root angulation in mind.

PMID- 24436946
TI  - Effects of different surface treatments on ceramic repairs with composite.
AB  - OBJECTIVE: To compare different surface treatments of lithium disilicate-based
      ceramic on bond strengths to composite. METHODS: Lithium disilicate-based ceramic
      microbars (1 mm * 1 mm * 6 mm) were produced and abraded using diamond (D) or
      CoJet sandblasting (C), etched using phosphoric acid (P) or hydrofluoric acid (H)
      and silanised (S). A total of 12 surface treatments were adopted: D, DP, DH, DS,
      DPS, DHS, C, CP, CH, CS, CPS and CHS. An adhesive resin (XP Bond) was then
      applied and a composite build-up was placed. All specimens were thermocycled
      5,000 times and submitted to microtensile bond strength test (MUTBS). Results
      were analysed using one-way analysis of variance and the Dunnett T3 test.
      Stereomicroscope and scanning electron microscopy were used to determine the
      failure modes. RESULTS: Surface roughening, acid etching and silanisation all
      have a significant influence on the ceramic-composite bond durability. Groups DH
      (30.7 +/- 6.5 MPa), DHS (32.0 +/- 8.2 MPa), CH (27.2 +/- 4.5 MPa) and CHS (29.2
      +/- 5.5 MPa) showed the highest MUTBS statistically. Groups DS (11.5 +/- 3.0 MPa)
      and DPS (9.7 +/- 2.2 MPa) had higher MUTBS than groups D (4.5 +/- 2.9 MPa) and DP
      (5.2 +/- 3.0 MPa), while groups C (1.7 +/- 0.7 MPa), CS (1.7 +/- 0.9 MPa), CP
      (1.7 +/- 0.6 MPa) and CPS (1.7 +/- 1.1 MPa) showed the lowest MUTBS. CONCLUSION:
      Hydrofluoric acid etching was effective in improving the bond strength of
      composite to lithium disilicate-based ceramic, regardless of the method of
      surface roughening and silanisation.

PMID- 24436947
TI  - Occupational exposure to blood and body fluids among dental personnel in a
      Chinese dental hospital.
AB  - OBJECTIVE: To determine the prevalence of occupational exposure (OE) occurring to
      dentists, dental nurses and senior dental students in a Chinese dental hospital
      and to assess associated factors with these exposures. METHODS: Data were
      collected through anonymous questionnaires, which were distributed to dentists,
      nurses, and senior dental students. RESULTS: All 205 dental personnel who
      voluntarily participated in the survey completed the questionnaire. Up to 71.2%
      of respondents experienced at least one OE to blood and body fluids (BBF) one
      year prior to this study. Dentists had a significantly higher incidence of OE
      than nurses (82.6% verse 60.8%), and a higher incidence of percutaneous injury
      than students (63.8% versus 41.7%). Sixty-seven percent of exposed dental
      personnel did not report the incidents and only 4.1% underwent postexposure blood
      tests. Although 97.6% of respondents wore gloves, more than half the subjects did
      not use protective goggles or masks during daily dental practice. CONCLUSION:
      There was a high level of OE and a significant incidence of underreporting among
      Chinese dental personnel, particularly in dentists. Inadequate use of personal
      protective equipment and ignorance about postexposure management were of great
      concern.

PMID- 24436948
TI  - Comparisons of in vitro penetration and adaptation of moisture tolerant resin
      sealant and conventional resin sealant in different fissure types.
AB  - OBJECTIVE: To compare the penetration and adaptation of a moisture tolerant resin
      based sealant with a conventional resin-based sealant in different occlusal
      fissure types in vitro by scanning electron microscopic (SEM) technique. METHODS:
      Fifty sound, intact extracted premolars and third molars were included. They were
      randomly and equally allocated to receive either Seal-Rite (conventional resin
      based sealant) or Embrace WetBond (moisture-tolerant resin-based sealant).
      Etching and sealant applications were performed as per manufacturers'
      instructions. Specimens were sectioned at the deepest part of the fissure and
      viewed under SEM. Under SEM, fissure types were classified as U, V, I, IK or
      inverted Y. SEM images were analysed using Biowizard image analysis software to
      measure penetration and adaptation. The data were statistically tested. RESULTS:
      U fissures showed the highest mean percentage penetration. V forms exhibited the
      best adaptation. IK forms showed the poorest percentage penetration and
      adaptation. Fissure form significantly affected adaptation but not penetration.
      Embrace WetBond penetrated better than Seal-Rite into all the fissures but
      adapted excellently only in U fissures. CONCLUSION: Fissure morphology
      significantly affected sealant adaptation. Moisture-tolerant Embrace WetBond was
      better than conventional Seal-Rite in penetration and adaptation into fissures.

PMID- 24436949
TI  - Inhibition of acidogenicity in dental plaque by sodium fluoride solution after
      sucrose rinse.
AB  - OBJECTIVE: To evaluate the effect of sodium fluoride rinse on sucrose-induced
      decrease in plaque pH with interdental plaque pH telemetry. METHODS: Six
      participants wearing partial lower prostheses incorporating a miniature glass pH
      electrode were included. The measurement of plaque pH was performed after 6 days
      of plaque accumulation. Three experiments were performed to test the effects of
      fluoride administered before (experiment I) or 10 min after (experiment II) and
      25 min after (experiment III) a sucrose rinse. In experiment I, the subjects
      rinsed with 0.05% NaF solution before rinsing with 10% sucrose to examine the
      effect of fluoride on the sucrose-induced pH drop. In experiment II, the subjects
      first rinsed with 10% sucrose and then followed no subsequent rinsing or rinsing
      with tap water 10 min after sucrose expectoration, or 0.05%, 0.02% or 0.01% NaF
      solution for 2 min. In experiment III, the subjects first rinsed with 10% sucrose
      and then 25 min after sucrose expectoration, they rinsed with 0.05% NaF for 2
      min. The plaque pH was continuously recorded for about 120 min. RESULTS: Without
      any subsequent rinses, the plaque pH decreased at 10 min to 4.36 and stayed below
      the critical pH 5.7 for about 85 min after the sucrose rinse. Subsequent water
      rinses showed little effect on the sucrose-induced decrease in plaque pH.
      Pretreatment of 0.05% NaF solution showed no effect on the subsequent sucrose
      induced pH drop. Subsequent rinses with NaF solutions at 10 min after the sucrose
      rinse inhibited the sucrose-induced pH drop in a dose-dependent manner.
      Subsequent rinses with NaF solutions after the sucrose rinse also significantly
      reduced the time below pH 5.7 and the area of plaque pH curve under 5.7 (AUC5.7).
      Furthermore, the AUC5.7 value (3.99) of 0.05% NaF rinse at 10 min after the
      sucrose rinse was much smaller than that (57.01) of 0.05% NaF rinse at 25 min
      after the sucrose rinse. CONCLUSION: Rinsing with 0.05% fluoride after
      carbohydrate consumption effectively reduced the acidogenicity of the plaque and
      could enhance the anticaries functions of fluoride.

PMID- 24436950
TI  - Effect of non-surgical periodontal therapy on serum levels of TNF-a, IL-6 and C
      reactive protein in periodontitis subjects with stable coronary heart disease.
AB  - OBJECTIVE: To evaluate the effects of periodontal non-surgical therapy on serum
      levels of the inflammatory cytokines in chronic periodontitis subjects with
      stable coronary heart disease. METHODS: Seventy-five subjects with both chronic
      periodontitis (CP) and stable coronary heart disease (CHD) were enrolled in the
      study. Forty subjects received periodontal nonsurgical treatment including oral
      hygiene instruction, scaling and root planing, whereas 35 subjects received oral
      hygiene instruction only. At baseline and 3 months after completion of
      periodontal treatment, clinical periodontal parameters were recorded. Serum
      levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C
      reactive protein (CRP), lipid profile markers and white blood cell count were
      assayed. Pearson's correlation analysis was applied to examine the correlation
      between the change of TNF-alpha, IL-6 and CRP levels and the change of
      periodontal parameters after non-surgical periodontal treatment. RESULTS: At
      baseline, there were no statistical differences in all clinical, biochemical
      parameters and cytokine levels between these two groups. Three months later in
      the treatment group, all clinical parameters improved significantly and the serum
      levels of TNF-alpha, IL-6, and CRP reduced significantly. Reduction of TNF-alpha
      was significantly positively correlated with the reduction of bleeding index and
      plaque index; reduction of IL-6 was significantly positively correlated with the
      reduction of clinical attachment loss; reduction of CRP was significantly
      positively correlated with the reduction of clinical attachment loss and plaque
      index. CONCLUSION: Non-surgical periodontal therapy decreased serum TNF-alpha, IL
      6 and CRP levels in CP subjects with stable CHD, which could help to reduce the
      inflammatory burden of stable coronary heart disease subjects.

PMID- 24436951
TI  - Prevalence of preeruptive intracoronal radiolucency in Chinese children from
      panoramic radiographs.
AB  - OBJECTIVE: To determine the prevalence of preeruptive intracoronal dentin defects
      in Chinese children from panoramic radiographs, and describe the imaging
      characteristics of these lesions. METHODS: A total of 707 panoramic radiographs
      with 8,171 unerupted permanent teeth were examined. Each unerupted tooth was
      examined with regard to the absence or presence of radiolucencies within the
      dentin of the crown. The location and size of the lesions were recorded. Also
      whether the lesion communicated with the pulp was noted. RESULTS: The prevalence
      of intracoronal radiolucency in the subjects was 0.85%, and the tooth prevalence
      of the anomaly was 0.7%. CONCLUSION: Panoramic radiographs may help in detecting
      the preeruptive intracoronal defect.

PMID- 24436952
TI  - Oral lichen sclerosus et atrophicus - literature review and two clinical cases.
AB  - Lichen sclerosus et atrophicus (LSA), also called Lichen sclerosus (LS) is a
      chronic, benign, depigmenting disease of the skin and mucous membranes, most
      frequently affecting genital mucosa and skin. Involvement of the oral mucosa
      without concurrent genital or skin lesions has very rarely been reported in the
      literature. Here we report on two Chinese women with LSA limited to the dorsum of
      the tongue, and describe the clinical manifestations and histopathological
      findings of these two patients. 

PMID- 24436953
TI  - Temperature change in the helicopter transport of trauma patients.

PMID- 24436954
TI  - Current Australian practice in the diagnosis and management of Barrett's
      oesophagus.

PMID- 24436955
TI  - Recovery after abdominal surgery: the peritoneum may be a key  therapeutic
      target.

PMID- 24436956
TI  - Response.

PMID- 24436957
TI  - Response.

PMID- 24436958
TI  - Quantitative Determination of Carthamin in Carthamus Red by 1H-NMR Spectroscopy.
AB  - Carthamus Red is a food colorant prepared from the petals of Carthamus tinctorius
      (Asteraceae) whose major pigment is carthamin. Since an authentic carthamin
      standard is difficult to obtain commercially for the preparation of calibration
      curves in HPLC assays, we applied (1)H-NMR spectroscopy to the quantitative
      determination of carthamin in commercial preparations of Carthamus Red. Carthamus
      Red was repeatedly extracted in methanol and the extract was dissolved in
      pyridine-d(5) containing hexamethyldisilane (HMD) prior to (1)H-NMR spectroscopic
      analysis. The carthamin contents were calculated from the ratios of singlet
      signal intensities at approximately sigma: 9.3 derived from H-16 of carthamin to
      those of the HMD signal at sigma: 0. The integral ratios exhibited good
      repeatability among NMR spectroscopic analyses. Both the intra-day and inter-day
      assay variations had coefficients of variation of <5%. Based on the coefficient
      of absorption, the carthamin contents of commercial preparations determined by
      (1)H-NMR spectroscopy correlated well with those determined by colorimetry,
      although the latter were always approximately 1.3-fold higher than the former,
      irrespective of the Carthamus Red preparations. In conclusion, the quantitative
      (1)H-NMR spectroscopy used in the present study is simple and rapid, requiring no
      carthamin standard for calibration. After HMD concentration has been corrected
      using certified reference materials, the carthamin contents determined by (1)H
      NMR spectroscopy are System of Units (SI)-traceable.

PMID- 24436959
TI  - Synthesis and in vitro testing of antimalarial activity of non-natural-type
      neocryptolepines: structure-activity relationship study of 2,11- and 9,11
      disubstituted 6-methylindolo[2,3-b]quinolines.
AB  - This report describes the synthesis and in vitro anti-malarial evaluations of
      certain C2 or C8 and C11-disubstituted 6-methyl-5H-indolo[2,3-b]quinoline
      (neocryptolepine congener) derivatives. To attain higher activities, the
      structure-activity relationship (SAR) studies were conducted by varying the kind
      of alkylamino or omega-aminoalkylamino stubstituents at C11 and with Cl at the C2
      position, or CO2Me at the C9 position. The anti-malarial activities of the tested
      compounds were significantly increased compared to the 11-non(alkylamino)
      derivatives. The 3-aminopropylamino group at C11 was further modified to urea and
      thiourea, which improved the cytotoxicity against normal cells. The best results
      were achieved with compounds 8 and 9d against the NF54 strain with the IC(50)/SI
      values as of 86 nM/20 and 317 nM/370, respectively. Furthermore, the compounds
      were tested for beta-haematin inhibition. Twelve were found to have IC(50) values
      below 100 uM and a linear correlation between the beta-haematin inhibition and
      cell growth inhibition in the NF54 strain was found for those derivatives with
      basic amino side chains. A second correlation was identified between the NF54
      activity and physico-chemical factors related to solvation and polarity.

PMID- 24436960
TI  - How many published cases of serious adverse events after yellow fever vaccination
      meet Brighton Collaboration diagnostic criteria?
AB  - OBJECTIVES: To perform a systematic review of all serious adverse events (SAEs)
      after yellow fever vaccination and to assess them according to Brighton
      Collaboration criteria. METHODS: Nine electronic databases were searched with the
      terms "yellow fever vaccine" and "adverse events" to 10 July 2013 (no
      language/date limits). Two reviewers independently assessed studies, entered
      data, and assessed cases with Brighton Collaboration criteria. RESULTS: One
      hundred and thirty-one cases met Brighton Collaboration criteria: 32 anaphylaxis,
      41 neurologic (one death), 56 viscerotropic (24 deaths), and 2 both neurologic
      and viscerotropic criteria. All SAEs occurred following first yellow fever (YF)
      vaccination. Two additional cases which met Brighton Collaboration criteria were
      proven due to wild virus. An additional 345 cases were presented with
      insufficient detail to meet Brighton Collaboration criteria:173 neurological, 68
      viscerotropic (24 deaths), 67 anaphylaxis, and 34 cases from a UK database and 3
      from a Swiss database described as "serious adverse events" but not further
      classified into neurologic or viscerotropic. A further 253 cases were excluded as
      presenting insufficient data to be regarded as yellow fever vaccine (YFV) related
      SAEs. CONCLUSIONS: One hundred and thirty-one cases met Brighton Collaboration
      criteria for serious adverse events after yellow fever vaccination. Another 345
      cases did not meet Brighton criteria and 253 were excluded as presenting
      insufficient data to be regarded as serious adverse events after YFV. There are
      likely to be cases in areas that are remote or with insufficient diagnostic
      resources that are neither correctly assessed nor not published.

PMID- 24436961
TI  - The Global Opioid Policy Initiative (GOPI) project to evaluate the availability
      and accessibility of opioids for the management of cancer pain in Africa, Asia,
      Latin America and the Caribbean, and the Middle East: introduction and
      methodology.
AB  - Opioid analgesics are critical to the effective relief of cancer pain. Effective
      treatment is predicated on sound assessments, individually tailored analgesic
      therapy, and the availability and accessibility of the required medications. In
      some countries, pain relief is hampered by the lack of availability or barriers
      to the accessibility of opioid analgesics. As the follow-up to a successful
      project to evaluate the availability and accessibility of opioids and regulatory
      barriers in Europe, the European Society for Medical Oncology (ESMO) and the
      European Association for Palliative Care (EAPC) undertook to expand their
      research to those parts of the world where data were lacking regarding these
      aspects of care, in particular Africa, Asia, the Middle East, Latin America and
      the Caribbean, and the states of India. This project has been undertaken in
      collaboration with the Union for International Cancer Control (UICC), the Pain
      and Policy Studies Group (PPSG) of the University of Wisconsin, and the World
      Health Organization (WHO), together with a consortium of 17 international
      oncology and palliative care societies. This article describes the study
      methodology.

PMID- 24436962
TI  - Methodology for in situ protection of aldehydes and ketones using trimethylsilyl
      trifluoromethanesulfonate and phosphines: selective alkylation and reduction of
      ketones, esters, amides, and nitriles.
AB  - A methodology for selective transformations of ketones, esters, Weinreb amides,
      and nitriles in the presence of aldehydes has been developed. The use of a
      combination of PPh(3)-trimethylsilyl trifluoromethanesulfonate (TMSOTf) promotes
      selective transformation of aldehydes to their corresponding, temporarily
      protected, O,P-acetal type phosphonium salts. Because, hydrolytic work-up
      following ensuing reactions of other carbonyl moieties in the substrates
      liberates the aldehyde moiety, a sequence involving aldehyde protection,
      transformation of other carbonyl groups, and deprotection can be accomplished in
      a one-pot manner. Furthermore, the use of PEt(3) instead of PPh(3) enables
      ketones to be converted in situ to their corresponding O,P-ketal type phosphonium
      salts and, consequently, selective transformations of esters, Weinreb amides, and
      nitriles in the presence of ketones can be performed. This methodology is
      applicable to various dicarbonyl compounds, including substrates that possess
      heteroaromatic skeletons and hydroxyl protecting groups.

PMID- 24436963
TI  - Two new pyrrolidine alkaloids, codonopsinol C and codonopiloside A, isolated from
      Codonopsis pilosula.
AB  - A new pyrrolidine alkaloid codonopsinol C (1), and pyrrolidine alkaloidal
      glycoside, codonopiloside A (2), were isolated from the roots of Codonopsis
      pilosula, along with four known pyrrolidine alkaloids, codonopsinol A (3),
      codonopsinol B (4), codonopyrrolidium B (5), and radicamine A (6). The structures
      of the new compounds were established by acid hydrolysis and spectroscopic
      methods. We describe those structures in this paper.

PMID- 24436964
TI  - Dipasperoside A, a novel pyridine alkaloid-coupled iridoid glucoside from the
      roots of Dipsacus asper.
AB  - A new pyridine alkaloid-coupled iridoid glucoside, dipasperoside A (1), and 20
      known compounds (2-21) were isolated from a water extract of Dipsacus asper
      roots. Compound 1 possessed a unique structural feature with a nicotinic acid
      nucleus coupled through C-5 with C-7 of a secoiridoid/iridoid glucoside dimer,
      and esterified with a C-7 hydroxyl group of an iridoid glucoside monomer. All
      isolates were evaluated for their inhibitory activity against nitric oxide (NO)
      production in a lipopolysaccharide (LPS)-activated murine macrophage cell line,
      RAW264.7.

PMID- 24436965
TI  - Four New 7,8-epoxycembranoids from a Chinese soft coral Lobophytum sp.
AB  - Four new 7,8-epoxycembranoids, namely (2S*,7S*,8S*,12R*,1Z,3E,10E)-7,8:2,16
      diepoxycembra-1(15),3,10-trien-12-ol (1), (2S*,7S*,8S*,11R*,1Z,3E)-7,8:2,16
      diepoxycembra-1(15),3,12(20)-trien-11-ol (2), (4S*,7S*,8S*,1Z,2E,11E)-16-acetoxy
      7,8-epoxycembra-1(15),2,11-trien-4-ol (3), and (7S*,8S*,15S*,1E,3E,11E)-7,8
      epoxycembra-1,3,11-trien-15,16-diol (4) were isolated from a Chinese soft coral
      Lobophytum sp., together with eleven known analogues 5-15. The structures of the
      new compounds were determined by extensive spectroscopic data analysis. All
      compounds were tested for the inhibitory effect on lipopolysaccharide (LPS)
      induced nitric oxide (NO) production in mouse peritoneal macrophages (PEMPhi).

PMID- 24436966
TI  - Disease research: Rare insights.

PMID- 24436968
TI  - Ictal alterations of consciousness during ecstatic seizures.
AB  - Patients with ecstatic epileptic seizures report an altered consciousness, which
      they describe as a sense of heightened perception of themselves - they "feel very
      present" - and an increased vividness of sensory perceptions. Recently, the
      anterior insula has been proposed as the region where these seizures originate,
      based on the results of ictal nuclear imaging in three patients, the first
      induction of ecstatic auras by electrical stimulation, and the functional
      characteristics of the anterior insula in neuroimaging literature. Specifically,
      the anterior insula is thought to play a key role in integrating information from
      within the body, the external world, as well as the emotional states. In
      addition, the anterior insula is thought to convert this integrated information
      into successive global emotional moments, thus enabling both the construct of a
      sentient self as well as a mechanism for predictive coding. As part of the
      salience network, this region is also involved in switching from mind wandering
      toward attentional and executive processing. In this review, we will summarize
      previous patient reports and recap how insular functioning may be involved in the
      phenomenon of ecstatic seizures. Furthermore, we will relate these hypotheses to
      the results from research on meditation and effects of drug abuse.

PMID- 24436967
TI  - Epilepsy and driving: potential impact of transient impaired consciousness.
AB  - Driving is an important part of everyday life for most adults, and restrictions
      on driving can place a significant burden on individuals diagnosed with epilepsy.
      Although sensorimotor deficits during seizures may impair driving, decreased
      level of consciousness often has a more global effect on patients' ability to
      respond appropriately to the environment. Better understanding of the mechanisms
      underlying alteration of consciousness in epilepsy is important for decision
      making by people with epilepsy, their physicians, and regulators in regard to the
      question of fitness to drive. Retrospective cohort and cross-sectional studies
      based on surveys or crash records can provide valuable information about driving
      in epilepsy. However, prospective objective testing of ictal driving ability
      during different types of seizures is needed to more fully understand the role of
      impaired consciousness and other deficits in disrupting driving. Driving
      simulators adapted for use in the epilepsy video-EEG monitoring unit may be well
      suited to provide both ictal and interictal data in patients with epilepsy.
      Objective information about impaired driving in specific types of epilepsy and
      seizures can provide better informed recommendations regarding fitness to drive,
      potentially improving the quality of life of people living with epilepsy.

PMID- 24436969
TI  - Implicit task sequence learning in patients with Parkinson's disease, frontal
      lesions and amnesia: the critical role of fronto-striatal loops.
AB  - The purpose of this study was to investigate the role of the fronto-striatal
      system for implicit task sequence learning. We tested performance of patients
      with compromised functioning of the fronto-striatal loops, that is, patients with
      Parkinson's disease and patients with lesions in the ventromedial or dorsolateral
      prefrontal cortex. We also tested amnesic patients with lesions either to the
      basal forebrain/orbitofrontal cortex or to thalamic/medio-temporal regions. We
      used a task sequence learning paradigm involving the presentation of a sequence
      of categorical binary-choice decision tasks. After several blocks of training,
      the sequence, hidden in the order of tasks, was replaced by a pseudo-random
      sequence. Learning (i.e., sensitivity to the ordering) was assessed by measuring
      whether this change disrupted performance. Although all the patients were able to
      perform the decision tasks quite easily, those with lesions to the fronto
      striatal loops (i.e., patients with Parkinson's disease, with lesions in the
      ventromedial or dorsolateral prefrontal cortex and those amnesic patients with
      lesions to the basal forebrain/orbitofrontal cortex) did not show any evidence of
      implicit task sequence learning. In contrast, those amnesic patients with lesions
      to thalamic/medio-temporal regions showed intact sequence learning. Together,
      these results indicate that the integrity of the fronto-striatal system is a
      prerequisite for implicit task sequence learning.

PMID- 24436971
TI  - Vestibular dysfunction and Alzheimer's disease.

PMID- 24436970
TI  - Altered visual-spatial attention to task-irrelevant information is associated
      with falls risk in older adults.
AB  - Executive cognitive functions play a critical role in falls risk-a pressing
      health care issue in seniors. In particular, intact attentional processing is
      integral for safe mobility and navigation. However, the specific contribution of
      impaired visual-spatial attention in falls remains unclear. In this study, we
      examined the association between visual-spatial attention to task-irrelevant
      stimuli and falls risk in community-dwelling older adults. Participants completed
      a visual target discrimination task at fixation while task-irrelevant probes were
      presented in both visual fields. We assessed attention to left and right
      peripheral probes using event-related potentials (ERPs). Falls risk was
      determined using the valid and reliable Physiological Profile Assessment (PPA).
      We found a significantly positive association between reduced attentional
      facilitation, as measured by the N1 ERP component, and falls risk. This
      relationship was specific to probes presented in the left visual field and
      measured at ipsilateral electrode sites. Our results suggest that fallers exhibit
      reduced attention to the left side of visual space and provide evidence that
      impaired right hemispheric function and/or structure may contribute to falls.

PMID- 24436972
TI  - Is memory stored in the brain neurons and is magnetite involved?

PMID- 24436973
TI  - The high heart health value of drinking-water magnesium.
AB  - Universal drinking water and beverages containing moderate to high levels of
      magnesium (10-100 ppm) could potentially prevent 4.5 million heart disease and
      stroke deaths per year, worldwide. This potential is calculated with 2010 global
      mortality figures combined with a recent quantification of water-magnesium's
      inverse association with heart disease and stroke mortality. The modern processed
      food diet, low in magnesium and spreading globally, makes this well-researched
      potential of drinking-water magnesium worth serious consideration, especially in
      areas where insufficient dietary intake of magnesium is prevalent.

PMID- 24436975
TI  - The teleost humoral immune response.
AB  - Over the past 10 years our knowledge of cellular and molecular dynamics of
      teleost humoral immunity has increased enormously to now include: the existence
      of multiple isotypes, affinity-driven modulation of antibody structure and
      function, the unique trafficking patterns of each stage of B cell differentiation
      (including the plasma blast, short-lived and long-lived plasma cell, and the
      memory cell). Unfortunately the work which has generated the bulk of this
      information has generally employed defined antigens rather than vaccines. Thus,
      the focus of this review is to relate these aspects of immunity that are
      requisite for a mechanistic understanding of the generation of prophylactic
      immunity to the necessary analysis of responses to vaccines and vaccine
      candidates.

PMID- 24436974
TI  - Benzodiazepine-like discriminative stimulus effects of toluene vapor.
AB  - In vitro studies show that the abused inhalant toluene affects a number of ligand
      gated ion channels.The two most consistently implicated of these are gamma
      aminobutyric acid type A(GABAA) receptors which are positively modulated by
      toluene and N-methyl-D-aspartate(NMDA) receptors which are negatively modulated
      by toluene. Behavioral studies also suggest an interaction of toluene with GABAA
      and/or NMDA receptors but it is unclear if these receptors underlie the abuse
      related intoxicating effects of toluene. Seventeen B6SJLF1/J mice were trained
      using a two-choice operant drug discrimination procedure to discriminate 10 min
      of exposure to 2000 ppm toluene vapor from 10 min of exposure to air. The
      discrimination was acquired in a mean of 65 training sessions. The stimulus
      effects of 2000 ppm toluene vapor were exposure concentration-dependent but
      rapidly diminished following the cessation of vapor exposure. The stimulus
      effects of toluene generalized to the chlorinated hydrocarbon vapor
      perchloroethylene but not 1,1,2-trichloroethane nor the volatile anesthetic
      isoflurane. The competitive NMDA antagonist CGS-19755, the uncompetitive
      antagonist dizocilpine and the glycine-site antagonist L701,324 all failed to
      substitute for toluene. The classical nonselective benzodiazepines midazolam and
      chlordiazepoxide produced toluene-like stimulus effects but the alpha 1 subunit
      preferring positive GABAA modulator zaleplon failed to substitute for toluene.
      The barbiturates pentobarbital and methohexital and the GABAA positive modulator
      neurosteroid allopregnanolone did not substitute for toluene. These data suggest
      that the stimulus effects of toluene may be at least partially mediated by
      benzodiazepine-like positive allosteric modulation of GABAA receptors containing
      alpha 2, 3 or 5 subunits.

PMID- 24436976
TI  - Mast cells in common wolffish Anarhichas lupus L.: ontogeny, distribution and
      association with lymphatic vessels.
AB  - The morphology, ontogeny and tissue distribution of mast cells were studied in
      common wolffish(Anarhichas lupus L.) at the larval, juvenile and adult life
      stages using light and electron-microscopy and immunohistochemistry. Fish were
      sampled at 1 day, 1, 2, 3, 4, 8 and 12 weeks post-hatching in addition to 6 and 9
      months and 2 years and older. From 8 weeks post-hatching, mast cells in common
      wolffish mainly appeared as oval or rounded cells 8-15 mm in diameter with an
      eccentrically placed, ovoid nucleus and filled with cytoplasmic granules up to
      1.2 mm in diameter. Granules were refractile and eosinophilic to slightly
      basophilic in H&E and stained bright red with Martius-scarlet-blue and purple
      with pinacyanol erythrosinate in formalin-fixed tissues. Mast cells stained
      positive for piscidin 4 and Fc epsilon RI by immunohistochemistry. From 1 day to
      4 weeks post-hatching, immature mast cell containing only a few irregularly sized
      cytoplasmic granules were observed by light and electron-microscopy in loose
      connective tissue of cranial areas. From 1 day post-hatching, these cells stained
      positive for piscidin 4 and Fc epsilon RI by immunohistochemistry. From 12 weeks
      post-hatching, mast cells showed a primarily perivascular distribution and were
      particularly closely associated with lymphatic vessels and sinuses. Mast cells
      were mainly located at the peripheral border of the adventitia of arteries and
      veins, while they were in intimate contact with the endothelium of the lymphatic
      vessels. Numerous mast cells were observed in the intestine. A stratum compactum,
      as described in salmonids, was not observed in wolffish intestine,nor were mast
      cells confined to a separate layer, a stratum granulosum. Lymphatic vessels
      consisting of endothelium, intimal connective tissue and a poorly developed basal
      lamina were observed in the intestine. Scanning electron microscopy was used to
      compare the structure and localization of intestinal mast cells of common
      wolffish and rainbow trout. Scanning electron microscopy also revealed
      endothelial surface features and confirmed the existence of three distinctly
      different types of vessels in the wolffish intestine. Rainbow trout mast cell
      granules appeared as intact globular structures while empty vacuoles were
      observed in common wolffish. Mast cells were closely associated with lymphatic
      vessels in common wolffish, but not in rainbow trout.

PMID- 24436977
TI  - Identification and expression analysis of differentially expressed genes from
      shrimp (Penaeus monodon) in response to low salinity stress.
AB  - Four suppression subtractive hybridization (SSH) cDNA libraries were constructed
      to identify differentially expressed salinity stress responsive genes of black
      tiger shrimp, Penaeus monodon exposed to low (3 ppt) salinity conditions. Forward
      and reverse SSH cDNA libraries were developed from the gill and gut tissues of
      shrimp and clones having inserts larger than 300 bp were unidirectionally
      sequenced. Based on the sequence homology search, the identified genes were
      categorized for their putative functions related to a wide range of biological
      roles, such as nucleic acid regulation and replication, immune response, energy
      and metabolism, cell signaling, cellular process, cytoskeleton and membrane
      structure, stress and osmoregulation. Gene expression levels in response to low
      salinity conditions at 2 weeks post salinity stress of thirteen selected
      differentially expressed genes identified from SSH cDNA libraries (14-3-3 like
      protein, crust in, lysozyme, arginine kinase, Nap/Kp-ATPase a-subunit,
      intracellular fatty acid binding protein, cathepsin B, anti-lipopolysaccharide
      factor, ferritin, ubiquitin conjugating enzyme E2, calreticulin, innexin 2 and
      heat shock protein 21) were analyzed by RT-PCR. The highest gene expression
      levels were observed for Nap/Kp-ATPase a-subunit (34.28-folds) in gill tissues,
      intracellular fatty acid binding protein (13.30-folds) in gut tissues and innexin
      2 (14.43-folds) in muscle tissues respectively. The differential and significant
      levels of gene expression indicate the functional role of these genes in shrimp
      salinity stress adaptive mechanisms.

PMID- 24436978
TI  - Differential effects of nomifensine and imipramine on motivated behavior in the
      runway model of intracranial self-stimulation.
AB  - A motivational deficit (the loss of pleasure or interest in previously rewarding
      stimuli) is one of the core symptoms of major depression, and valid models
      evaluating the motivational effects of drugs are needed. It was recently
      demonstrated that the priming stimulation effect in the runway model of
      intracranial self-stimulation (ICSS) can be used as a model system to study the
      motivational effects of drugs. However, the characteristics of this novel
      experimental model have not been fully clarified. In this study, we investigated
      the effects of nomifensine and imipramine in the runway ICCS model, forced swim
      tests, and locomotor activity tests to differentiate motivation from affective
      like states. Nomifensine dose-dependently increased running speed on the runway
      and decreased immobility time in the forced swim test. In contrast, imipramine
      decreased running speed on the runway although it also decreased immobility time
      in the forced swim test. In addition, the motivation-enhancing effect of
      nomifesine in the runway model was completely inhibited by pretreatment with the
      dopamine receptor antagonist haloperidol, although nomifensine-induced increases
      in locomotion were not affected by haloperidol. These results demonstrate that
      nomifensine displays motivation-enhancing and antidepressant-like effects. In
      addition, the motivational effects of nomifensine in the runway ICSS model are
      primarily mediated by dopamine receptors and enhancements of motivated behavior
      do not simply reflect hyperlocomotion.

PMID- 24436979
TI  - Anxiolytic-like effect of mirtazapine mediates its effect in the median raphe
      nucleus.
AB  - Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA),
      blocks the alpha2-adrenergic autoreceptors and heteroreceptors, which are
      responsible for controlling noradrenaline and 5-hydroxy-tryptamine (5-HT)
      release. Though preclinical and clinical studies have shown that mirtazapine
      exerts an anxiolytic action, its precise brain target sites remain unclear. In
      the present study, we investigated the brain area(s) in which mirtazapine exerts
      its anxiolytic-like effects on the expression of contextual conditioned freezing
      in rats. Mirtazapine (3 MUg/site) was directly injected into three brain
      structures, the median raphe nucleus (MRN), hippocampus and amygdala. Freezing
      behavior tests were carried out 10 min after injections. Our results showed that
      the intra-MRN injection of mirtazapine reduced freezing significantly, whereas
      injections into the hippocampus or the amygdala did not. In addition, the intra
      MRN injection of mirtazapine did not affect locomotor activity. These results
      suggest that the anxiolytic-like effect of mirtazapine might be mediated by its
      action on the MRN.

PMID- 24436980
TI  - Power to the people.

PMID- 24436981
TI  - Cool heads needed.

PMID- 24436982
TI  - V is for vortex.

PMID- 24436983
TI  - Development: Time to leave GDP behind.

PMID- 24436984
TI  - Regulation: The FDA is overcautious on consumer genomics.

PMID- 24436985
TI  - The dopamine D(3) receptor antagonist YQA14 that inhibits the expression and drug
      prime reactivation of morphine-induced conditioned place preference in rats.
AB  - Increasing evidence suggests that the mesolimbic dopamine system plays a critical
      role in opioid addiction. However, there is currently no standard drug treatment
      for opioid addiction. Growing preclinical evidence indicates that the dopamine
      D(3) receptor antagonists are the potential anti-addiction pharmacotherapeutic
      agents based on animal models of multiple drug addiction. In this study, we
      investigated the inhibitory effects of YQA14, a novel dopamine D(3) receptor
      antagonist with a high affinity and selectivity for dopamine D(3) receptor, using
      morphine-induced conditioned place preference (CPP) in rats. The results
      suggested that YQA14 (6.25-25 mg/kg; intraperitoneal, i.p.) decreased the
      expression of morphine (10 mg/kg, s.c.)-induced CPP in a dose-related manner but
      did not influence the acquisition of morphine-induced CPP. At a 25 mg/kg dose of
      YQA14, it also notably inhibited the reactivation of morphine-priming CPP. These
      findings suggest that YQA14 is a potential agent for anti-opioid addiction which
      warrants further study and development.

PMID- 24436986
TI  - Degradation of beta-blockers in hospital wastewater by means of ozonation and
      Fe2+/ozonation.
AB  - This study investigates the degradation of the beta-blockers in hospital
      wastewater by direct ozonation and Fe2+/ozonation with a focus on measurements at
      different initial pHs and Fe2+ concentrations, and the determination of kinetic
      constants. The results showed that these 'emerging contaminants' were completely
      degraded, when the removal rate of organic matter reached 30.6% and 49.1% for
      ozonation and Fe2+/ozonation, respectively. Likewise, the aromaticity removal
      rates were 63.4% and 77.9% for ozonation and Fe2+/ozonation, respectively. The
      experimental design showed that pH was the variable which had the greatest effect
      on the Fe2+/ozonation. The kinetic constants of atenolol, metoprolol and
      propranolol degradation by direct ozonation complied with pseudo-first-order
      conditions, while Fe2+/ozonation was suited to a biphasic degradation model. The
      k obs tended to rise when the pH increases; propranolol showed high k obs, which
      can be attributed to the naphthalene group (an electron-rich moiety). The
      identification of degradation products was carried out in aqueous solution using
      HPLC-MS2, followed by a suggestion of degradation pathways by means of ozonation.
      The degradation products proved to be dependent on the initial pH, and followed
      pathways that are based on direct ozonolysis and free radicals.

PMID- 24436987
TI  - Protective effects of chronic resveratrol treatment on vascular inflammatory
      injury in steptozotocin-induced type 2 diabetic rats: role of NF-kappa B
      signaling.
AB  - Type 2 diabetes mellitus (T2DM) is associated with an increased risk of
      macrovascular disease. Epidemiological studies suggest that plant polyphenol
      resveratrol (REV) is associated with reduced risk of cardiovascular diseases.
      Since chronic inflammatory and endotheliar cell activation play a critical role
      in vascular aging and atherogenesis, we evaluated whether REV can inhibit
      inflammatory-induced vascular injury in T2DM. We found that REV (50 mg/kg/d) can
      regulate glucose and lipid metabolism, improve insulin resistance and vascular
      permeability, and protect against the foam cells and cholesterol crystals
      formation in arterial vessel walls of T2DM rats. The protective effects of REV
      were consistent with the decrease in nuclear translocation of nuclear factor
      kappa B (NF-kappa B) and there down-regulation of interleukin-1 beta (IL-1beta)
      and interleukin-6 (IL-6) levers in blood and tumor necrosis factor-alpha (TNF
      alpha), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant
      protein-1 (MCP-1) expressions in vascular wall. In addition, REV (10 and 100
      nmol/L) treatment protected cultured endothelial cells against increases in the
      expression of TNF-alpha, ICAM-1, and MCP-1 mRNA and protein induced by high
      glucose via inhibiting nuclear translocation of NF-kappa B p65. The specific NF
      kappa B inhibitor pyrrolidine dithiocarbamate- (PDTC-) or small interfering RNA
      directed against NF-kappa B p65-mediated downregulation of NF-kappa B p65 was
      further enhanced by REV (100 nmol/L) in the human endothelial cell line EZ.hy926.
      In conclusion, these observations suggest that chronic treatment of T2DM rats
      with REV attenuates the inflammatory injury of the vascular wall and the effects
      are associated with down-regulation of the NF-kappa B signal pathway.

PMID- 24436988
TI  - Glyburide, a K(+)(ATP)channel blocker, improves hypotension and survival in
      anaphylactic shock induced in Wistar rats sensitized to ovalbumin.
AB  - Allergens can induce anaphylactic shock and death due to serve hypotension.
      Potassium channel blockers (K(+)(ATP)) such as glyburide (GLY) induce
      vasoconstriction. The effect of (K(+)(ATP)) channel blockers on anaphylactic
      shock is poorly understood. Objective of the study was to test the hypothesis
      that GLY reduces hypotension induced in anaphylactic shock and increases
      survival. Rats were grouped into: G1-N=Naive; G2-SC=Sensitized-Control; G3
      SG=Sensitized-GLY (glyburide 40 mg/kg); G4-SE=Sensitized-EPI (epinephrine 10
      mg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was
      induced by i.v. injection of OVA. Treatments were administered intravenously 5
      min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time
      (MST) were measured for 60 min following OVA injection and treatments
      administration. At the end of the experiment, blood withdrawal was performed to
      measure plasma levels of histamine, leukotriene B(4) (LTB(4)), prostaglandin E(2)
      (PGE(2)) and prostaglandin F(2) (PGF(2)). Additionally blood gas (paO2, paCO2,
      SaO2) and electrolytes (Na(+), K(+) and Ca (++)) were measured. MAP was normal in
      G1-N; severe hypotension, negative inotropic and short MST were observed in G2
      SC; normalization of MAP, with lesser negative inotropism and increased MST were
      observed in G3-SG; full recovery was observed in G4-SE. Histamine level was
      significantly higher in G2-SC; reduced in G3-SG and G4-SE. PGE(2) increased in G3
      SG; PGF(2) increased in G2-SC and G3-SG. Na(+) and Ca (++) concentration
      decreased in sensitized rats but reversed in treated groups, without change in
      K(+) concentration. In conclusion, our data suggest that administration of GLY
      reduced hypotension and increases survival time in rat anaphylactic shock.

PMID- 24436989
TI  - Involvement of nitric oxide production in the impairment of skin blood flow
      response to local cooling in diabetic db/db mice.
AB  - An enhanced vasocontrictor activity of cutaneous vessels participates in the
      reduction of skin blood flow induced by cooling. The present study investigated
      changes in the local response to cooling in hyperglycemic conditions. Male
      diabetic db/db and control C57BL/6J mice, anaesthetized with pentobarbitone, were
      treated with tetrodotoxin for eliminating the sympathetic nerve tone and
      artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser
      Doppler flowmetry. Cooling the air temperature around the foot reduced PSBF in a
      temperature-dependent manner in control and db/db mice. The PSBF reduction was
      significantly smaller in db/db mice than in control mice. Phentolamine, a non
      selective alpha-antagonist, bunazosin, a selective alpha1-antagonist, MK-912, a
      selective alpha2C-antagonist, and Y-27632, a Rho-kinase inhibitor, significantly
      inhibited the PSBF reduction induced by cooling to 15  degrees C in both mice and
      the inhibitory effects were comparable between these mice. The cooling-induced
      PSBF reduction was also significantly inhibited by N(omega)-nitro-L-arginine, an
      inhibitor of nitric oxide synthase, in control mice; however, the inhibitory
      effect of N(omega)-nitro-L-arginine was not observed in db/db mice. The reduction
      of PSBF induced by the intraarterial administration of adrenaline was comparable
      between control and db/db mice both before and after the treatment with N(omega)
      nitro-L-arginine. It is thus likely that the reduction of skin blood flow induced
      by local cooling might be partly mediated by a decrease in endothelium-derived
      nitric oxide production, and that an impairment of the nitric oxide production
      might be related to reduced vasocontrictor response to cooling in db/db mice.

PMID- 24436990
TI  - Antagonist profile of ibodutant at the tachykinin NK(2) receptor in guinea pig
      isolated bronchi.
AB  - In this study we have characterized the pharmacological profile of the non
      peptide tachykinin NK(2) receptor antagonist ibodutant (MEN15596) in guinea pig
      isolated main bronchi contractility. The antagonist potency of ibodutant was
      evaluated using the selective NK(2) receptor agonist [betaAla8]NKA(4-10)-mediated
      contractions of guinea pig isolated main bronchi. In this assay ibodutant (30,
      100 and 300 nM) induced a concentration-dependent rightward shift of the
      [betaAla8]NKA(4-10) concentration-response curves without affecting the maximal
      contractile effect. The analysis of the results yielded a Schild-plot linear
      regression with a slope not different from unity (0.95, 95% c.l. 0.65-1.25),
      thus, indicating a surmountable behavior. The calculated apparent antagonist
      potency as pK(B) value was 8.31 +/- 0.05. Ibodutant (0.3-100 nM) produced a
      concentration-dependent inhibition of the nonadrenergic-noncholinergic (NANC)
      contractile response induced by electrical field stimulation (EFS) of intrinsic
      airway nerves in guinea pig isolated main bronchi. At the highest concentration
      tested (100 nM) ibodutant almost abolished the EFS-induced bronchoconstriction
      (95 +/- 4% inhibition), the calculated IC(50) value was 2.98 nM (95% c.l. 1.73
      5.16 nM). In bronchi from ovalbumin (OVA) sensitized guinea pigs ibodutant (100
      nM) did not affect the maximal contractile response to OVA, but completely
      prevented the slowing in the fading of the motor response induced by
      phosphoramidon pretreatment linked to the endogenous neurokinin A release.
      Altogether, the present study demonstrates that ibodutant is a potent NK(2)
      receptor antagonist in guinea pig airways.

PMID- 24436992
TI  - Author response.

PMID- 24436991
TI  - Novel isonahocol E(3) exhibits anti-inflammatory and anti-angiogenic effects in
      endothelin-1-stimulated human keratinocytes.
AB  - Endothelin-1 (ET-1) is reported to be a potent mitogenic and pro-angiogenic
      factor that plays a vital role in both physiological and pathological processes.
      ET-1 is implicated in dermal cell proliferation and skin disorders, such as
      psoriasis and atopic dermatitis. ET-1, endothelin ET(A) receptor, and endothelin
      ET(B) receptor could be potential targets for developing specific therapeutics to
      treat such disorders. Here, we provide the first report that an isonahocol [2,-5
      hihydroxy-3-(13-hydroxy-3,-7,-11,-15-tetramethyl-12-oxo-hexadeca-2,-6,-14
      trienyl)-phenyl]-acetic acid methyl ester (isonahocol E(3)) from the brown algae
      Sargassum siliquastrum has functional antagonistic activities against ET-1
      induced inflammatory and proangiogenic effects. Isonahocol E(3) significantly
      inhibited ET-1-induced cell proliferation, as well as inflammatory mediators,
      such as interleukin-6 (IL-6) and interleukin-8 (IL-8) and tumor necrosis factor
      alpha (TNF-alpha), and pro-angiogenic factors including metalloproteinases in
      immortalized human keratinocytes. We also found that isonahocol E(3) reduced
      expression level of endothelin ET(A) receptor, and endothelin ET(B) receptor as
      well as suppressed ET-1 induced extracellular signal-regulated kinase (ERK)
      phosporylation. Taken together, our results suggest that isonahocol E(3) can
      exert anti-inflammatory and anti-angiogenic activities at least by regulating the
      expression of ET-1 receptors and ERK signaling pathway.

PMID- 24436993
TI  - Effects of hyperbaric oxygen on MMP-2 and MMP-9 expression and spinal cord edema
      after spinal cord injury.
AB  - AIMS: To evaluate the effects of hyperbaric oxygen (HBO) therapy on MMP-2 and MMP
      9 expression and spinal cord edema after acute spinal cord injury (SCI). MAIN
      METHODS: Ninety-six healthy adult Sprague - Dawley rats were randomly divided
      into 4 groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was subdivided
      into 4 subgroups of 6 rats each: 24 h, 48 h, 72 h, and 5 d post-injury. The
      expression levels of matrix metalloproteinase-2 (MMP-2), MMP-9, interleukin (IL
      6), and vascular endothelial growth factor (VEGF) were measured using ELISA. The
      water content of the spinal cord was also measured by Elliot equation. KEY
      FINDING: MMP-2 and MMP-9 levels and spinal cord water content increased
      significantly in the SCI group compared to those in the sham and sham + HBO
      groups at different time points after SCI (P < 0.01). The MMP-2 level was
      significantly different between the SCI and SCI + HBO groups at 72 h after SCI (P
      < 0.05), while the MMP-9 level was significantly different at 48 h, 72 h, and 5 d
      (P < 0.05). The water content of the spinal cord was significantly higher in the
      SCI group at 5 d after SCI (P < 0. 01). MMP-2 (P < 0.05) and MMP-9 (P < 0.01)
      levels were positively correlated with spinal cord water content. SIGNIFICANCE:
      HBO reduced SCI-induced spinal cord edema, stabilized the blood-spinal cord
      barrier, and promoted recovery of neuronal function by down regulating the
      expression of IL-6, MMP-2, and MMP-9 and up regulating the expression of VEGF.

PMID- 24436994
TI  - Synthesis and biological evaluation of 3-hydroxymethyl-5-(1H-1,2,3-triazol)
      isoxazolidines.
AB  - A synthetic approach towards a series of 3-hydroxymethyl-5-(1H-1,2,3
      triazol)isoxazolidines has been reported, according to a procedure based on the
      cycloaddition reaction, under microwave irradiation, of a nitrone with 1-vinyl
      triazoles, prepared by a click reaction of azides with alkynes. Biological tests
      show that the synthesized compounds are able to inhibit proliferation of
      follicular and anaplastic human thyroid cancer cell lines, with IC50 values
      ranging from 3.87 to 8.76 lM. The obtained compounds induce caspase-3 activation
      and DNA fragmentation prevalently in follicular human thyroid cancer cell lines.

PMID- 24436995
TI  - Synthesis and cytotoxicity of pyranonaphthoquinone natural product analogues
      under bioreductive conditions.
AB  - We have synthesised a focused library of derivatives of natural products
      containing the pyranonaphthoquinone moiety including the first report of such a
      scaffold with an appended tetrazole functionality. Examples include kalafungin
      derivatives as well as analogues of nanaomycin and eleutherin. These compounds
      were assessed for cytotoxic activation by breast cancer cell lines engineered to
      express the prototypic human one- and two-electron quinone bioreductive enzymes,
      NADPH: cytochrome P450 oxidoreductase (POR) and NAD(P)H: quinoneoxidoreductase 1
      (NQO1; DT-diaphorase), respectively. Several compounds were observed to be
      cytotoxic at sub-micromolar level and a pattern of increased aerobic potency was
      observed in cells over expressing POR. A subset of analogues was assessed under
      anoxic conditions, where cytotoxicity was reduced, implicating redox cycling as a
      major mechanism of toxicity. The substrate specificity for reductive enzymes is
      relevant to the future design of bioreductive prodrugs to treat cancer.

PMID- 24436997
TI  - Monthly report on dracunculiasis cases, January-October 2013.

PMID- 24436996
TI  - Progress towards poliomyelitis eradication in Nigeria, January 2012-September
      2013.

PMID- 24436998
TI  - 2013 College of Diplomates of the American Board of Pediatric Dentistry Annual
      Meeting: pediatric cardiology: an overview.
AB  - Congenital heart defects can be classified as those characterized by a left to
      right shunt, a right to left shunt, obstruction to flow from the heart, or
      abnormalcies of myocardial contraction and relaxation. Left to right shunts
      include atrial and ventricular septal defects, and patent ductus arteriosus.
      Right to left shunts include transposition of the great arteries, tetralogy of
      Fallot, tricuspid atresia among others. These defects result in cyanosis. Lesions
      causing obstruction to blood flow from the heart include aortic and pulmonary
      valve stenosis and coarctation of the aorta. Disorders of myocardial contraction
      and relation include hypertrophic, dilated, and restrictive cardiomyopathies. In
      addition, the author will discuss innocent heart murmur and Kawasaki's disease.

PMID- 24436999
TI  - Author's response.

PMID- 24437000
TI  - Do U.S. regulations allow more than minor increase over minimal risk pediatric
      research? Should they?

PMID- 24437002
TI  - What is life answered in terms of properties and activities of auto-cooperative
      assemblies of molecules, atoms, ions and electrons called nano-protoplasm.

PMID- 24437001
TI  - A pregnancy testing policy for women enrolled in clinical trials.

PMID- 24437003
TI  - A 2004 unanswered letter to the Economist magazine requesting a retraction (and
      apology).
AB  - This is a copy of (the bulk of) a letter I mailed on May 13, 2004 to Sir Robert
      P. Wilson, President, and three editors of the magazine, the Economist. With the
      letter, I also sent each recipient a copy of my latest book, "Life at the Cell
      and Below-Cell Level" as a gesture of good will.

PMID- 24437004
TI  - Preface for the updated Chinese translation of Gilbert N. Ling's Life at the Cell
      and Below-Cell Level.

PMID- 24437005
TI  - [The elderly patient at the heart of care].

PMID- 24437006
TI  - [Management of oral anticoagulants by elderly patients at home].
AB  - Improving the management of a vitamin K antagonist (VKA) treatment helps to
      reduce the risk of haemorrhage. To assess the treatment methods and the quality
      of education of elderly patients, a telephone survey was carried out in 2011 of
      100 patients treated with a VKA. The patients, or main carers managing the
      treatment at home, have adequate knowledge of their treatment. The education of
      elderly patients therefore seems to be a reasonable and viable objective.

PMID- 24437007
TI  - [Dental care for dependent elderly people].
AB  - In 1995, the faculty of dental surgery of Paris-Descartes University set up a
      scheme whereby students at the end of their basic training offer their assistance
      and skills to institutions caring for dependent elderly people. This article
      presents a 2011 assessment of the difficulties encountered by the students and
      nurses' awareness of the importance of integrating oral hygiene into patients'
      overall care.

PMID- 24437008
TI  - [The coordinator nurse in nursing homes, at the crossroads of care].
AB  - Working as a coordinator nurse in a nursing home requires numerous personal and
      professional qualities. This key position at the heart of the coordination of
      care deserves greater recognition.

PMID- 24437009
TI  - [Rehabilitation and the elderly are not incompatible].

PMID- 24437010
TI  - [Care and prognosis of elderly people in intensive care].
AB  - The absence of formal documentation on the benefits of intensive care for elderly
      people explains the lack of standardised practices while their numbers are
      increasing in intensive care departments. The improved prognosis of acute
      pathologiesjustifyingtheir admission to intensive care units requires a multi
      disciplinary approach and an optimisation of all the care structures upstream and
      downstream of a stay in intensive care. This must be based on the collective
      definition of the care pathway for these elderly patients requiring instead of in
      an intensive care unit.

PMID- 24437011
TI  - [The importance of geriatrics-intensive care collaboration].
AB  - As is the case with all medical and surgical departments, the proportion of
      elderly patients in intensive care departments is gradually increasing.At
      Ambroise Pare hospital, in Boulogne-Billancourt, a natural collaboration has been
      set up between intensive care staff and geriatricians to adapt the care provided
      and to limit situations of unreasonable therapeutic obstinacy, notably thanks to
      a standardised gathering of information.

PMID- 24437012
TI  - [A nursing team's approach].
AB  - The proportion of elderly people admitted to intensive care has increased over
      recent years. Apart from the questions relating to the medical treatment,
      admission criteria and level of care, it is sometimes difficult to identify the
      consequences for the non-medical staff of an intensive care department of two
      units (12 intensive care beds and 8 continuing care beds).

PMID- 24437013
TI  - [The admission of elderly people to intensive care].
AB  - The criteria for admitting elderly people to intensive care are dependent on a
      number of factors, relating to the patients, the organisation of the hospital and
      the characteristics of the intensive care staff.This article assesses the current
      situation in a context where longer life expectancy is resulting in an increase
      in the number of elderly patients.

PMID- 24437014
TI  - [Advance directives, the delicate use of its freedom].
AB  - Advance directives are clearly formulated in the Leonetti law of 2005. They
      specify a person's choices about their health care if they are unable to express
      their wishes.They set out the patient's end-of-life decisions with regard to
      limiting or stopping treatment. Valid for 3 years and renewable, they can be
      modified or revoked at any time.

PMID- 24437015
TI  - [Bibliography. Rehabilitation and the elderly].

PMID- 24437016
TI  - [Non-small cell lung cancer in the elderly].

PMID- 24437017
TI  - [Patient education and the elderly patient].

PMID- 24437018
TI  - We don't need a chained Consumer Price Index.

PMID- 24437019
TI  - Examining cultural competence in health care: implications for social workers.
AB  - This article examines and unpacks the "black box" of cultural competence in
      health interventions with racial and ethnic minority populations. The analysis
      builds on several recent reviews of evidence-based efforts to reduce health
      disparities, with a focus on how cultural competence is defined and
      operationalized. It finds that the use of multiple similar and indistinct terms
      related to cultural competence, as well as the lack of a mutually agreeable
      definition for cultural competence itself, has resulted in an imprecise concept
      that is often invoked but rarely defined and only marginally empirically
      validated as an effective health intervention. This article affirms the
      centrality of cultural competence as an essential values-based component of
      optimal social work practice, while also suggesting future directions for
      operationalizing, measuring, and testing cultural competence to build an evidence
      base on whether and how it works to reduce health disparities.

PMID- 24437020
TI  - Mental health and poverty in the inner city.
AB  - Rapid urbanization globally threatens to increase the risk to mental health and
      requires a rethinking of the relationship between urban poverty and mental
      health. The aim of this article is to reveal the cyclic nature of this
      relationship: Concentrated urban poverty cultivates mental illness, while the
      resulting mental illness reinforces poverty. The authors used theories about
      social disorganization and crime to explore the mechanisms through which the
      urban environment can contribute to mental health problems. They present some
      data on crime, substance abuse, and social control to support their claim that
      mental illness reinforces poverty. The authors argue that, to interrupt this
      cycle and improve outcomes, social workers and policymakers must work together to
      implement a comprehensive mental health care system that emphasizes prevention,
      reaches young people, crosses traditional health care provision boundaries, and
      involves the entire community to break this cycle and improve the outcomes of
      those living in urban poverty.

PMID- 24437021
TI  - Online training on fetal alcohol spectrum disorders for court-appointed special
      advocates volunteers.
AB  - Fetal alcohol spectrum disorders (FASDs) are a leading cause of developmental
      disabilities. Children within the child welfare system are five to 10 times more
      likely than other children to experience these symptoms. Court Appointed Special
      Advocates (CASA) volunteers are uniquely positioned to identify these children
      and refer them for assessment and services. This study used a one-group pretest
      posttest design to assess the impact of a three-hour online FASDs training on
      CASA workers' knowledge of FASDs and their comfort and confidence in identifying
      children with FASDs for referral, advocating for them, and linking them to
      services. The training and assessment measures were completed by 338 CASA
      volunteers and staff from 55 CASA locations in Texas. Wilcoxon matched-pairs
      tests and paired t tests were used to assess change in each of the dependent
      measures. All comfort and confidence items showed significant improvement from
      pretest to posttest; there was also a significant improvement in knowledge. These
      results support the potential of this online training to enhance CASA volunteers'
      ability to help children with FASDs.

PMID- 24437022
TI  - Mind-body techniques, race-ethnicity, and depression among urban senior center
      participants.
AB  - As the older adult population grows and becomes more diverse, more of its members
      are turning to complementary and alternative medicine (CAM). There are mixed
      findings regarding racial and ethnic differences in the use of CAM. This article
      explores racial and ethnic differences in use of a category of CAM known as mind
      body techniques (MBT) among senior center participants with symptoms of
      depression. It also examines the relationship between use of MBT and depression
      severity. A cross-sectional survey was conducted with a representative sample of
      senior center participants in New York City, from which a subsample of those with
      depressive symptoms was drawn. Racial and ethnic differences in MBT use were
      identified, as was a significant negative relationship between MBT use and
      depression severity. African American elders were more likely to have used MBT
      than other racial or ethnic groups. When controlling for race or ethnicity,
      health status, and barriers to medical care, predictors of depression severity
      included health status, experiencing barriers to medical care, and Hispanic
      identity. Findings suggest that being female or younger is associated with a
      higher likelihood of using CAM. Contrary to some prior research, education level
      was not associated with use of MBT.

PMID- 24437023
TI  - Tobacco training in clinical social work graduate programs.
AB  - The leading cause of preventable death, in the most vulnerable segments of
      society, whom social workers often counsel, is cigarette smoking. The purpose of
      this study was to assess tobacco smoking cessation training in clinical social
      work programs. A valid 21-item questionnaire was sent to the entire population of
      189 clinical graduate social work programs identified by the Council on Social
      Work Education. A three-wave mailing process was used to maximize the return
      rate. Directors from 112 clinical social work programs returned completed
      questionnaires (61 percent). The majority (91 percent) of directors reported
      having never thought about offering formal smoking cessation training, and only
      nine of the programs (8 percent) currently provided formal smoking cessation
      education. The three leading barriers to offering smoking cessation education
      were as follows: not a priority (60 percent), not enough time (55 percent), and
      not required by the accrediting body (41 percent). These findings indicate that
      clinical social work students are not receiving standardized smoking cessation
      education to assist in improving the well-being of their clients. The national
      accrediting body for graduate clinical social work programs should consider
      implementing guidelines for smoking cessation training in the curriculums.

PMID- 24437024
TI  - Breast and cervical cancer screening for women with intellectual disabilities.

PMID- 24437025
TI  - If not now, when? The case for treating nonspecific back pain with psychosocial
      interventions.

PMID- 24437026
TI  - Employment-based retirement plan participation: geographic differences and
      trends, 2012.

PMID- 24437027
TI  - Enrollment up, docs get SGR respite.

PMID- 24437028
TI  - 2013 brought reform, gridlock, glitches and accountable care.

PMID- 24437029
TI  - Taking the EHR penalty: more doc offices may opt out.

PMID- 24437030
TI  - Partners in health.

PMID- 24437031
TI  - A holiday wish list.

PMID- 24437032
TI  - The time is now to fix SGR.

PMID- 24437034
TI  - Building narrow networks that work. Interview by Merrill Goozner.

PMID- 24437033
TI  - Hospital pushes for quiet on the set.

PMID- 24437035
TI  - Leading the plunge into the risk pool. Interview by Melanie Evans.

PMID- 24437036
TI  - Rewarding quality--the 10 most- and least-improved hospitals.

PMID- 24437037
TI  - Breaking news.

PMID- 24437038
TI  - The write stuff.

PMID- 24437039
TI  - Your Medicare map.

PMID- 24437040
TI  - Football & family.

PMID- 24437042
TI  - Open wide.

PMID- 24437041
TI  - Avoiding food fights.

PMID- 24437043
TI  - Vape me out to the ball game!

PMID- 24437044
TI  - Lead, allergen, and pesticide levels in licensed child care centers in the United
      States.
AB  - The First National Environmental Health Survey of Child Care Centers was
      conducted to provide information about lead, allergen, and pesticide levels in
      licensed U.S. child care centers. Lead levels were measured in settled dust,
      paint, and play area soil; indoor allergen levels were measured in settled dust;
      and pesticide residues were measured on indoor surfaces and in play area soil.
      Fourteen percent of centers had significant lead hazards, suggesting that an
      estimated 470,000 children under age six (approximately 10% of all children in
      licensed centers) attend centers with significant lead hazards. Approximately 5%
      of centers had levels of allergens associated with asthma and allergic
      conditions. Three-quarters of centers had pesticides applied (either indoors or
      outdoors) during the previous year. Although most centers did not appear to
      present risks from lead and allergens, some centers did have unsafe levels of
      these contaminants. These conclusions cannot be generalized to unlicensed child
      care arrangements.

PMID- 24437045
TI  - Onsite wastewater system nitrogen contributions to groundwater in coastal North
      Carolina.
AB  - The objective of the study described in this article was to evaluate the nitrogen
      contributions from two onsite wastewater systems (sites 1 and 2) to groundwater
      and adjacent surface waters in coastal Beaufort County, North Carolina.
      Groundwater levels and water quality parameters including total nitrogen,
      nitrogen species, temperature, and pH were monitored from October 2009 to May
      2010. Nitrogen was also tested in groundwater from deeper irrigation or drinking
      water wells from the two sites and six additional neighboring residences. Mean
      total nitrogen concentrations in groundwater beneath onsite wastewater systems 1
      and 2 were 34.3 +/- 16.7 mg/L and 12.2 +/- 2.9 mg/L, respectively, and
      significantly higher than background groundwater concentrations (< 1 mg/L).
      Groundwater in the deeper wells appeared not to be influenced by the onsite
      systems. Groundwater nitrogen concentrations typically decreased with distance
      down-gradient from the systems, but were still elevated relative to background
      conditions more than 15 m from the systems and near the estuary. This was a
      pioneering effort to better understand the link of onsite systems, the fate of
      nitrogen in the environment, and public health.

PMID- 24437046
TI  - Public health implications of animals in retail food outlets.
AB  - Growing societal interest to permit animals into retail food outlets presents
      both risks and benefits to the dining public and consumers. This article
      summarizes a literature review that evaluated the associated potential public
      health issues related to this subject. Using the EBSCOhost research protocol and
      Google search engines between March 2010 and June 2011, the authors have compiled
      and synthesized scientific research articles, empirical scientific literature,
      and publicly available news media. While pets are known carriers of bacteria and
      parasites, among others, the relative risk associated with specific pet-human
      interactions in the dining public has yet to be established in a clear and
      consistent manner. Much of the available health-risk-factor evidence reflects
      pets in domestic conditions and interaction with farm animals. Special
      consideration is recommended for vulnerable populations such as children,
      asthmatics, the elderly, pregnant women, and the immunocompromised.

PMID- 24437048
TI  - Across the country: what's happening in environmental health.

PMID- 24437047
TI  - State health agency workforce shortages and implications for public health: a
      case study of restaurant inspections in Louisiana.
AB  - The study described in this article evaluated the effects of public health
      workforce cuts on routine food safety inspections and the occurrence of critical
      violations. Routine inspection information was collected from two Louisiana
      databases for permanent food establishments categorized as risk category 3 or 4
      in East Baton Rouge Parish, Louisiana, for the years 2005, 2007, and 2009. The
      length of time between routine inspections nearly quadrupled from 2005 to 2009.
      For risk category 4 establishments, a significant increase occurred in the
      proportion of inspections that resulted in a critical violation between the three
      years. The amount of time between routine inspections was significantly higher
      for inspections that resulted in a critical violation versus those that did not.
      Lastly, the amount of time between routine inspections, an establishment's risk
      category, and history of complaint were found to have significant predictive
      effects on the incidence of a critical violation during a routine inspection,
      although results varied by year. Study results indicate that decreased workforce
      capacity in Louisiana may negatively affect the outcomes of routine food safety
      inspections.

PMID- 24437049
TI  - Spotlight on ATSDR: exposure investigations.

PMID- 24437051
TI  - The great freelancer movement: eight reasons why your next job will be a project.

PMID- 24437050
TI  - The use of public health informatics to improve environmental health practice.

PMID- 24437052
TI  - Assessment of foodborne illness outbreak response and investigation capacity in
      U.S. Environmental Health Food Safety Regulatory Programs.

PMID- 24437053
TI  - The future of environmental health.

PMID- 24437054
TI  - 3 ways your staff will change.

PMID- 24437055
TI  - Embracing change.
AB  - Whether small or large, rural or urban, public or private, health care
      organizations have no choice but to face change and embrace it. Hospital leaders
      must be proactive and make the most of the opportunities ahead of them.

PMID- 24437056
TI  - Equity of care: the business imperative.

PMID- 24437057
TI  - In this together: hospitals unite around common foe: READMISSIONS.

PMID- 24437058
TI  - As team-based care becomes the norm, hospitals seek ways to address problem
      physicians.

PMID- 24437059
TI  - Wellness: can a rewards program motivate healthier behaviors in patients?

PMID- 24437060
TI  - Lets innovate: new center aims to accelerate information exchange.

PMID- 24437061
TI  - Rural, safety net hospitals brace for changes under ACA.

PMID- 24437062
TI  - Building an IT bridge with post-acute providers.

PMID- 24437063
TI  - Building a community of care providers.

PMID- 24437064
TI  - What, no wait?
AB  - The push is on to stop wasting patients' time--from registration to discharge,
      from the ED to the physician's office. Hospitals are using a variety of tactics
      to improve throughput and take a significant bite out of wait times.

PMID- 24437065
TI  - Way too much of a good thing. Interview by Paul Barr.

PMID- 24437066
TI  - 8 tips to manage staff across the ages.

PMID- 24437067
TI  - Managing points of access.

PMID- 24437068
TI  - Technology facilitates change in managing access to health care facilities.

PMID- 24437070
TI  - Dressed with dignity.

PMID- 24437069
TI  - Infection prevention: hospitals step it up.

PMID- 24437071
TI  - Clinicians and culture play important roles.

PMID- 24437072
TI  - [Defence mechanisms and coping strategies in men and women: a comparative and
      structural study based on the artistic production of people suffering from a
      break-up of their life project].
AB  - A comparative study of men and women suffering from a break-up of their life
      project allowed us examining the typically female and male manners to cope with
      trauma, anxiety, guilt, depression and internal destructivity. In a first stage,
      an exploratory study was focussed on 206 subjects, belonging to several clinical
      subgroups: people living in great precarity and long-term unemployed people,
      asylum seekers and refugees, drug addicts, prisoners and people coming out of
      prison. Secondly, arts therapeutic sessions were proposed with the aim of helping
      the participants finding an outlet to their situation. The artistic production
      (drawings and stories induced by music) was analysed with the help of original
      rating scales, constructed in a phenomenological and structural perspective. We
      will present a synthesis of our qualitative observations, as well as some results
      of typological and structural studies, computed with the help of non parametric
      statistical procedures on the data of N = 93 participants. The results allow us
      pointing to gender differences and defining typically male and female coping
      styles. Differential indications for psychotherapy can be extracted from these
      analyses.

PMID- 24437073
TI  - Management of acute diverticulitis in a tertiary care institution.
AB  - BACKGROUND: Diverticular disease of the left colon is a common disease, mainly in
      the population over 50 years of age. The surgical management of acute
      diverticulitis is remains controversial, especially in severe forms. OBJECTIVE:
      This study aimed to evaluate the results of laparoscopic surgery for diverticular
      disease in a tertiary care institution with a specialist interest in minimally
      invasive surgery. DESIGN: All patients who had elective laparoscopic
      sigmoidectomy for diverticulitis within eight years at University Hospital of
      Luxembourg were selected from a retrospective database to evaluate laparoscopic
      benefit in moderate and severe disease. RESULTS: A total of 155 patients were
      divided in two groups: Moderate Acute Diverticulitis (MAD) and Severe Acute
      Diverticulitis (SAD) respectively. The short-term outcomes, after laparoscopic
      sigmoidectomy, were evaluated. There were not important differences between two
      groups. CONCLUSIONS: The laparoscopic management of diverticular disease after
      moderate and severe crisis gives same benefits and short-term outcomes are
      similar. Elective Laparoscopic surgery is actually the standard of care for
      moderate and severe diverticular disease in our institution.

PMID- 24437074
TI  - Music and elderly.
AB  - Since more than 3 decades now, music with seniors (or younger persons), either as
      an educational or recreational activity, but also as a therapeutically approach
      has progressed. Even nowadays, in the medical field, more and more studies prove
      its efficiency as complementary therapy with no known side-effects. The areas
      where music therapy has a positive outcome, reach from pulmonary disorders to a
      lot of neurological chronic diseases, including aphasia, dementia or Parkinson.
      And at the end of life, music therapy has found a remarkable place for expressing
      or supporting strong emotional feelings. Evidence-based results on physiological
      and hormonal changes will also be reviewed.

PMID- 24437075
TI  - [The reduction of stroke risk, risk of myocardial infarction and death by healthy
      diet and physical activity].
AB  - There is no doubt that a healthy diet and regular physical activity improve risk
      factors for cerebro-cardio-vascular disease and death. However, there is less
      evidence from prospective randomised controlled trials that they also reduce the
      actual risk of stroke, myocardial infarction and death. The only evidence from
      randomised controlled trials is, that a mediterranean diet with nuts and/or
      native olive oil considerably reduces stroke risk by 47% respectively 31%,
      however not the risk of myocardial infarction and death. A low-fat diet, a low
      salt diet, and the addition of omega-3 fatty acids have no influence. In case of
      severe obesity with a BMI of > 34-38 kg/m2, weight reduction is the priority, if
      necessary by means of bariatric surgery. In longitudinal studies mortality (
      29%), stroke (-34%), and myocardial infarction (-29%) could thus be reduced.
      Regular physical activity, whether endurance or more intense activity, leads to
      weight loss and improved vascular risk factors. An independent impact on stroke,
      myocardial infarction and mortality has not yet been demonstrated in prospective
      studies (double-blinding being impossible). Nevertheless, several epidemiological
      meta-analyses with observation durations of 4 to 28 years using data of up to 880
      000 persons, indicate that there is a 2-3 fold risk reduction of cerebro-cardio
      vascular death and global mortality in people with regular physical activity
      versus sedentary behaviour.

PMID- 24437076
TI  - Multidisciplinary management of a gastric metastasis of uveal melanoma presenting
      12 years after enucleation.

PMID- 24437077
TI  - Seventh International Conference on Fertility Control for Wildlife.

PMID- 24437078
TI  - Contraception has gone to the coyotes (Canis latrans).
AB  - Coyotes (Canis latrans) are predators of livestock. Current management programs,
      primarily lethal control, are ineffective for long-term management of predation.
      Controlling reproduction of coyotes may reduce depredations if territory fidelity
      is maintained by breeding pairs. Surgical sterilization is successful in altering
      predatory behaviors of coyotes but may provide a challenge for field
      implementation. An alternative approach is the development of a one-time non
      transferable chemical contraceptive. This research is investigating the efficacy
      of a single high dose treatment of a sustained release gonadotropin-releasing
      hormone agonist, deslorelin, on coyotes as a long term contraceptive. Male
      coyotes were administered 47 mg deslorelin subcutaneously. Preliminary data show
      full suppression of the reproductive axis for over 12 mo as indicated by complete
      absence of sperm.

PMID- 24437079
TI  - Accelerated follicle depletion in vitro and in vivo in Sprague-Dawley rats using
      the combination of 4-vinylcyclohexene diepoxide and triptolide.
AB  - Rodent pests cause major damage to the world's agricultural crops and food
      stores. Rodenticides used since World War II did not lead to sustained reduction
      of rodent populations, and so fertility control is becoming attractive because
      rats reproduce with great efficiency. Chemical acceleration of ovarian failure
      via oral dosing also would improve management of rat pest populations. The
      chemical 4-vinylcyclohexene diepoxide (VCD) is orally efficacious, causing
      depletion of nonregenerating primordial ovarian follicles of Sprague-Dawley rats.
      However, to cause rapid reduction in pups in the first breeding cycle after
      dosing, all stages of ovarian follicle development must be targeted. To achieve
      this goal, the Chinese herb triptolide was tested because it can precipitate
      apoptosis and deplete growing follicles. The impact of triptolide was tested in
      cultured postnatal day 4 Sprague-Dawley rat pup ovaries. Triptolide at 5 nM
      caused 100% primordial, primary, and secondary follicle depletion after 8 days of
      culture, compared to 38% follicle depletion caused by VCD at 30 microM. Next, a
      palatable rat bait was developed, containing 1% VCD with increasing
      concentrations of triptolide at 25, 50, and 100 microg/kg body weight. Rats ate
      an average 3-6% of their body weight/day over 15 feeding days. Two days after the
      end of baiting, rats were euthanized to conduct necropsies and collect ovaries to
      count all follicular stages and corpora lutea. At 50 microg triptolide/kg body
      weight, there was significant reduction of all follicular stages; primordial
      follicles were 50% lower, secondary follicles were 64% lower, antral follicles
      were 80% lower, and there were no corpora lutea. These results suggest that
      combining VCD and triptolide in an oral bait leads to significantly compromised
      rat ovarian function and reduced ovulations, and is likely to reduce pup
      production.

PMID- 24437080
TI  - Laparoscopic vasectomy in African savannah elephant (Loxodonta africana);
      surgical technique and results.
AB  - Several small, enclosed reserves in southern Africa are experiencing significant
      elephant population growth, which has resulted in associated environmental damage
      and changes in biodiversity. Although several techniques exist to control
      elephant populations, e.g., culling, relocation, and immunocontraception, the
      technique of laparoscopic vasectomy of free-ranging bull elephants was
      investigated. Bilateral vasectomies were performed in 45 elephants. Of these
      elephants, one died within 24 hr of recovery and two had complications during
      surgery but recovered uneventfully. Histologic examination confirmed the resected
      tissue as ductus deferens in all the bulls. Most animals recovered uneventfully
      and showed no abnormal behavior after surgery. Complications recorded included
      incisional dehiscence, 1 full-thickness and 2 partial-thickness lacerations of
      the large intestine, and initial sling-associated complications, for example,
      deep radial nerve paresis. One bull was found dead 6 weeks after surgery without
      showing any prior abnormal signs. Vasectomy in free-ranging African bull
      elephants may be effectively performed in their normal environment. The surgical
      procedure can be used as a realistic population management tool in free-ranging
      elephants without major anesthetic, surgical, or postoperative complications.

PMID- 24437081
TI  - Immunocontraception of captive exotic species: V. Prolonged antibody titers in
      Dall sheep (Ovis dalli dalli) and domestic goats (Capra hircus) immunized with
      porcine zona pellucida.
AB  - Native porcine zona pellucida (PZP) immunocontraception has been used to inhibit
      fertility in more than 80 species of ungulates, although the duration of
      contraception efficacy varies among species in both Perissodactyla and
      Artiodactyla. This study examined anti-PZP antibody titers in Dall sheep and
      domestic goats at the Milwaukee County Zoo, and also Himalayan tahr and Armenian
      Mouflon sheep at the San Diego Zoo Safari Park, and, for comparison, Altai
      wapiti, lowland wisent, Javan banteng, and southern pudu at the San Diego Zoo
      Safari Park, all were given a primer dose and booster dose of PZP. Of the San
      Diego Zoo Safari Park animals, the 4 comparison species demonstrated the typical
      1-yr pattern of anti-PZP antibodies, whereas the Armenian sheep and Himalayan
      tahr showed prolonged (2-3 yr) antibody responses after a single primer and
      booster dose. The Dall sheep and domestic goats had significantly longer
      durations of antibody titers (3 yr) from a single year's treatment (primer plus
      booster). Analysis of the data indicates that Armenian sheep, Himalayan tahr,
      Dall sheep, and domestic goats have prolonged responses, and are more sensitive
      to PZP in that they produce a protracted antibody response.

PMID- 24437082
TI  - Reproductive health surveillance in zoo and wildlife medicine.
AB  - For over 25 years, the Reproductive Health Surveillance Program has collected,
      processed, evaluated, and archived reproductive tracts from nondomestic mammals
      submitted by zoos. The analysis of the data from this archive has been used to
      recognize lesions associated with exposure to certain contraceptives; but
      arguably more importantly, to also document naturally occurring lesions. The
      goals of this program are to enhance the reproductive management of captive and
      free-ranging species by providing information about the effects of various
      contraceptives and to provide basic information regarding the natural
      reproductive histories and naturally occurring lesions in male and female zoo
      animals.

PMID- 24437083
TI  - An economic model demonstrating the long-term cost benefits of incorporating
      fertility control into wild horse (Equus caballus) management programs on public
      lands in the United States.
AB  - In recent years, the Bureau of Land Management's (BLM) Wild Horse and Burro
      Management program costs have increased dramatically due to a rise in the number
      of animals removed from public lands coupled with significantly decreased
      adoption rates. To assist with development and implementation of effective, cost
      containing management programs, a robust economic model to project the costs and
      optimize outcomes of various management scenarios was created. For example,
      preliminary demonstration model runs show that by gradually replacing "removal
      only" programs with contraception-and-removal programs on one hypothetical Herd
      Management Area (HMA), the BLM could save about US$8 million over 12 years while
      maintaining an area target population of 874 horses. Because the BLM estimates
      that more than 38,000 wild horses roam on 179 HMAs in the United States, the use
      of this economic model could result in a cost-savings of tens of millions of
      dollars if applied broadly across all HMAs.

PMID- 24437084
TI  - Managing wildlife with contraception: why is it taking so long?
AB  - Biologists have been testing wildlife contraceptives in the field for nearly a
      half century. Although effective new contraceptive agents have been identified,
      new delivery technologies developed, and some success with population management
      demonstrated, progress in this area should be further along. Why is it taking so
      long? First, the task is complex. Most drugs and vaccines fail in development.
      The technical leaps from in vitro to in vivo, from controlled studies to field
      studies, from effectiveness in individuals to management of populations, are all
      formidable and frequent failures are inevitable. Testing the long-acting
      contraceptives required for successful population management demands experiments
      that take 3-5 yr to complete. Development of wildlife contraceptives has been
      further hampered by the lack of large-scale investment and the complex and
      shifting regulatory landscape that often greets novel enterprises. But there has
      also been focused resistance to the implementation of wildlife contraceptive
      studies and to the dissemination of results such studies have produced. This
      phenomenon, which sociologists label "socially constructed ignorance," has taken
      a variety of forms including denial of research permits, omission from research
      reports and management documents, and repetition of misleading or false
      information in public forums and the media. The persistence and effectiveness of
      this social resistance suggest that the ethical foundation of wildlife
      contraception is incomplete. As the institutional affiliations of participants of
      the 7th International Conference on Fertility Control for Wildlife confirmed,
      wildlife contraception has its ethical roots in the animal welfare and integrated
      pest-management communities. Absent from the discussion are the conservation
      community and the values they represent. To secure societal acceptance of
      wildlife contraception as a management technique, researchers and advocates for
      wildlife contraception must address conservation issues and build an ethical
      foundation that balances concern for individual animals and human needs with
      concern for the health of biologic communities.

PMID- 24437085
TI  - State-level approaches to managing the use of contraceptives in wildlife in the
      United States.
AB  - Several fertility control agents have recently been registered with the U.S.
      Environmental Protection Agency for management of wildlife or other free-ranging
      animals. The registration of GonaCon Immunocontraceptive Vaccine for use in white
      tailed deer (Odocoileus virginianus) and OvoControl for use in Canada geese
      (Branta canadensis) and pigeons (Columba livia) has caused state wildlife and
      land management agencies to review their regulatory authority over the use of
      contraceptives in wildlife. As a result, many states are taking steps to ensure
      legislation or policies are current with emerging technologies. This article
      examines the various approaches states are taking to regulate the use of
      contraceptives. Regardless of the final regulatory approach, biological, social,
      economic, and political implications must all be discussed as this new tool is
      introduced into the field of ona wildlife management. Thoughtful consideration of
      all aspects of wildlife contraceptive use will lead to the development of sound,
      best management practices for current and future products.

PMID- 24437086
TI  - Lack of spatial and behavioral responses to immunocontraception application in
      African elephants (Loxodonta africana).
AB  - Opinions are divided as to whether human intervention to control elephant
      (Loxodonta africana) population growth is desirable, partly because of elephant
      welfare concerns. Female contraception through immunization with porcine zona
      pellucida (PZP) proteins is viable. The effects of sustained use and application
      of the PZP vaccine on elephant behavioral and spatial responses were examined by
      evaluating herd ranging, fission-fusion dynamics, association patterns, and
      reproductive and sexual behaviors. Minimal change was anticipated as a result of
      long calf dependence on and association with cows, a reduced but not indefinite
      0% growth rate and the known mechanism of action of PZP vaccines, and minimal
      expected change in resource requirements necessitating behavioral or spatial use
      adaptations. Although behavioral effects identified in previous hormonal
      contraceptive trials were evident, it was demonstrated that immunocontraception
      caused no prolonged behavioral, social, or spatial changes over the 11-yr study
      period. Individually identified elephants were monitored from 1999 to 2011.
      Minimal, short-term social disruption, with temporary changes to the herds' core
      ranges, was observed during the annual treatment events, particularly in the
      first three treatment years, when vaccinations were conducted exclusively from
      the ground. Thereafter, when vaccinations were conducted aerially, minor
      disruptions were confined to the morning of administration only. Despite
      sustained treatments resulting in demographic changes of fewer calves being born,
      treatments did not alter spatial range use, and no adverse interherd-intraherd
      relations were observed. Similarly, resource requirements did not change as
      calving still occurred, although in fewer numbers. It was concluded that PZP
      immunocontraception has no detectable behavioral or social consequences in
      elephants over the course of 11 yr, providing a convincing argument for the use
      of sustained immunocontraception in the medium to long term as an important tool
      for elephant management. Behavioral consequences of alternative management
      approaches should all receive similar scrutiny to enable managers to make
      informed decisions when weighing management interventions.

PMID- 24437087
TI  - Single-treatment porcine zona pellucida immunocontraception associated with
      reduction of a population of white-tailed deer (Odocoileus virginianus).
AB  - Previous reports have demonstrated gradual reductions of white-tailed deer
      (Odocoileus virginianus) populations through immunocontraception, with
      stabilization occurring after 2-4 yr of treatment, and subsequent reductions of 6
      10% annually. These studies employed porcine zona pellucida (PZP) vaccines that
      required two initial treatments and annual retreatments. From 2005 to 2010, 258
      adult and yearling female deer on Fripp Island, South Carolina, were treated with
      one of several PZP preparations designed to produce 2+ yr of effective
      contraception with a single treatment. These included several preparations of
      SpayVac and of native PZP-adjuvant emulsion plus PZP and QA-21 in timed-release
      pellets. Deer were chemically immobilized, ear-tagged, and administered initial
      treatments by hand in February-March. Some treated deer were boosted remotely
      with PZP-adjuvant emulsion 1.5 - 4.5 yr after initial treatments. Ground-based
      distance sampling was used to estimate deer population density at Fripp Island, a
      resort community, and at a relatively undeveloped neighboring control site,
      Hunting Island. Most vaccine preparations tested reduced fawning rates by 75% to
      95% for at least 1 yr. From 2005 to 2011, deer density on Fripp Island declined
      by 50%, from 72 deer/km(2) to 36 deer/km(2), an average annual reduction of 11%.
      In contrast, population density on the Hunting Island control site fluctuated
      between 2005 and 2011, averaging 23 deer/km(2) (range, 19-28 deer/km(2)).
      Population declines on Fripp Island were associated with an increase in the
      proportion of treated females and with a progressive decrease in winter fawn:doe
      ratios, from 1.21 fawns/doe in 2005 to 0.19 fawns/doe in 2010. Winter fawn:doe
      ratios averaged 1.36 fawns/doe (range, 0.84 - 1.62 fawns/doe) at the Hunting
      Island control site. Annual survivorship averaged approximately 79% among ear
      tagged females. The rate at which deer populations diminished in association with
      PZP treatments on Fripp Island was higher than that seen at other study sites,
      although the reasons for the more rapid decline on Fripp Island are not well
      understood.

PMID- 24437088
TI  - Twenty years of immunocontraceptive research: lessons learned.
AB  - The National Wildlife Research Center (NWRC) began immunocontraception vaccine
      research by testing porcine zona pellucida (PZP) on white-tailed deer (Odocoileus
      virginianus). Early PZP research demonstrated that PZP induced infertility;
      however, increased length of the rut was observed in PZP-treated deer. An
      alternative vaccine using a keyhole limpet hemocyanin-gonadotropin-releasing
      hormone (KLH-GnRH) conjugate formulated with modified Freund's adjuvant was
      developed at NWRC. Suppression of GnRH has reduced reproduction in both sexes but
      is most effective in females. This vaccine was effective in preventing
      contraception in female deer for several years after a prime and boost. Due to
      adverse side effects of Freund's adjuvant, NWRC developed a new adjuvant called
      AdjuVac, a mineral oil/surfactant adjuvant with the addition of Mycobacterium
      avium as an immunostimulant. The price of KLH prompted a search for a more
      economical hemocyanin carrier protein for the GnRH peptide. Blue protein, derived
      from the mollusk Concholepas concholepas, proved to be a successful option.
      Formulation improvements resulted in a vaccine that can be effective as a single
      injection for multiple years, now called GonaCon. GonaCon is registered with the
      Environmental Protection Agency (EPA) for use in white-tailed deer in
      urban/suburban areas and for wild horses (Equus caballus) and burros (Equus
      asinus). Future GonaCon applications may include reducing reproduction to manage
      populations of other wildlife species, such as prairie dogs (Cynomys
      ludovicianus) in urban areas and suppressing reproduction to reduce the spread of
      venereal diseases such as brucellosis. Research is being conducted to develop a
      GnRH vaccine used in combination with the rabies vaccine to control population
      growth in free-roaming dogs, with the secondary effect of managing the spread of
      rabies. The EPA would regulate all these uses. Research is also ongoing on a GnRH
      vaccine to delay the onset of adrenocortical disease in pet ferrets (Mustela
      putorius), a use regulated by the United States Department of Agriculture.

PMID- 24437089
TI  - Dose and durational effects of the gonadotropin-releasing hormone agonist,
      deslorelin: the male rat (Rattus norvegicus) as a model.
AB  - Gonadotropin-releasing hormone (GnRH) agonists are routinely used to suppress the
      reproductive axis of many mammals, especially in zoos. Current treatments are
      reversible. There is a need to develop nonreversible agents, and this study
      investigates the effects of high-dose and long-duration exposure to the GnRH
      agonist, deslorelin, in the rat model. Studies indicate that the follicle
      stimulating hormone (FSH) gonadotropin is predominantly affected, and following
      high-dose exposure to deslorelin for a long duration, the ability of gonadotropes
      to synthesize FSH may be compromised, perhaps permanently. Understanding the
      mechanisms by which such persistent suppression of FSH occurs may facilitate the
      development of novel next-generation contraceptives. It is hypothesized that
      direct testicular effects of GnRH agonists may play a critical role in the
      efficacy of GnRH agonists in male contraception.

PMID- 24437090
TI  - From the pens to the field: real-world wildlife contraception.
AB  - There are only two nonlethal approaches with which to manage wildlife
      populations: remove excess individuals or decrease reproductive rates. In the
      case of wild horse management, the latter has already been shown to be a more
      humane and less costly approach. Contraception has been known for many years to
      be effective in wild horses with regard to both fertility and population
      alteration. Field testing under real-world management situations is a critical
      aspect of wildlife contraception assessment. Field testing also requires
      documentation to justify eventual large-scale use of fertility control in
      population management. Furthermore, it is likely that full support by the
      managing agencies and acceptance of fertility control by the public will not
      occur until success has been demonstrated at the population level in the field.
      Because the transition from laboratory and captive animal trials to the real
      world of field research and testing of management potential in free-ranging
      wildlife is both essential and difficult, we identify considerations for
      optimizing success in the field, especially for controlling wild horse and white
      tailed deer populations. This study identified the following categories for
      assessment: 1) field-specific logistics and tactics (including access to and
      identification of horses, censuses, pregnancy testing, and behavior monitoring),
      2) training of field personnel and managers (including vaccine biology,
      preparation and delivery, and basic field methodology), 3) essential field
      considerations for enabling management (including population variables,
      environmental variables, and modeling), and 4) pitfalls of field contraception.
      In this assessment, we will highlight the capability for coincident pursuit of
      research and management and will explore field considerations applicable to many
      species where fertility control has potential as a management tool.

PMID- 24437091
TI  - Applying clinically proven human techniques for contraception and fertility to
      endangered species and zoo animals: a review.
AB  - Reversible contraception that does not alter natural behavior is a critical need
      for managing zoo populations. In addition to reversible contraception, other
      fertility techniques perfected in humans may be useful, such as in vitro
      fertilization (IVF) or oocyte and embryo banking for endangered species like
      amphibians and Mexican wolves (Canis lupus baileyi). Furthermore, the genetics of
      human fertility can give a better understanding of fertility in more exotic
      species. Collaborations were established to apply human fertility techniques to
      the captive population. Reversible vasectomy might be one solution for reversible
      contraception that does not alter behavior. Reversible approaches to vasectomy,
      avoiding secondary epididymal disruption, were attempted in South American bush
      dogs (Speothos venaticus), chimpanzees (Pan troglodytes), gorillas (Gorilla
      gorilla), Przewalski's horse (Equus przewalski poliakov), and Sika deer (Cervus
      nippon) in a variety of zoos around the world. These techniques were first
      perfected in > 4,000 humans before attempting them in zoo animals. In vitro
      fertilization with gestational surrogacy was used to attempt to break the vicious
      cycle of hand rearing of purebred orangutans, and egg and ovary vitrification in
      humans have led to successful gamete banking for Mexican wolves and disappearing
      amphibians. The study of the human Y chromosome has even explained a mechanism of
      extinction related to global climate change. The best results with vasectomy
      reversal (normal sperm counts, pregnancy, and live offspring) were obtained when
      the original vasectomy was performed "open-ended," so as to avoid pressure
      induced epididymal disruption. The attempt at gestational surrogacy for
      orangutans failed because of severe male infertility and the lack of success with
      human ovarian hyperstimulation protocols. Vitrification of oocytes is already
      being employed for the Amphibian Ark Project and for Mexican wolves. Vasectomy
      can be a reversible contraception option in zoo animals, even in endangered
      species. Ongoing use of gamete and embryo freezing may salvage vanishing species.

PMID- 24437092
TI  - Romance without responsibilities: the use of the immunocontraceptive porcine zona
      pellucida to manage free-ranging bison (Bison bison) on Catalina Island,
      California, USA.
AB  - Prior to 2010, the introduced population of American bison (Bison bison) on Santa
      Catalina Island, California, was managed through the shipment of surplus bison to
      private ranches, Native American reservations, and livestock auctions on the
      mainland. In response to escalating costs, transport-induced stress to the
      animals, and ecologic impacts associated with high bison numbers on-island
      between shipments, the use of the immunocontraceptive vaccine porcine zona
      pellucida (PZP) as a fertility control option for managing the population was
      investigated. Between 2009 and 2012, a total of 64 bison cows (> or =1 yr old)
      received primer inoculations of 100 microg PZP emulsified with 0.5 ml Freund's
      modified adjuvant (FMA) delivered through a combination of intramuscular
      injections by hand (50 bison cows) during roundups and via field darting (14
      bison cows). Pre-rut booster inoculations of 100 microg PZP emulsified with 0.5
      ml Freund's incomplete adjuvant (FIA) were administered exclusively via field
      darting in 2010, 2011, and 2012 to 45, 48, and 61 bison cows (> or =1 yr old),
      respectively. During the present study, 38 adult cows (marked and unmarked)
      received one or more PZP inoculations during their first, second, or third
      trimesters of pregnancy, and of these individuals, 35 successfully produced
      calves. Low pregnancy values detected in the remaining three cows have been
      attributed to residual progesterone associated with unsuccessful fertilization.
      The 2010 pretreatment calving rate (calves born per cow) determined via direct
      observation was 67.4% (29 calves from 43 cows). Through the use of PZP, the
      calving rate was reduced to 10.4% by 2011 and to 3.3% by 2012. Considering the
      annual mortality rate of 2-5% documented during this study, the results
      demonstrate the potential of PZP use as an effective nonlethal tool for
      controlling population growth in free-ranging bison.

PMID- 24437093
TI  - The political and social barriers for contraception in pest birds: a case study
      of Ovocontrol (nicarbazin).
AB  - In a joint program, Innolytics and the U.S. Department of Agriculture/Animal and
      Plant Health Inspection Service National Wildlife Research Center collaborated in
      the development of nicarbazin as an avian contraceptive, initially for resident
      Canada geese and subsequently for feral pigeons. Unfortunately, the introduction
      of the original goose product in 2005 was a commercial failure. Political and
      social barriers effectively thwarted attempts to establish the new technology
      with any meaningful market success. Although the market adoption of the pigeon
      contraceptive has been less difficult, the product still encounters significant
      social and political obstacles and opposition. Given the focus on instant results
      and gratification, the introduction of contraceptive technology for birds has
      been challenging and broad market acceptance remains elusive. Nevertheless,
      especially for short-lived and rapidly reproducing species, customers continue to
      replace outdated or ineffective techniques with the safer and more effective
      contraceptive tool.

PMID- 24437094
TI  - The use of contraception as a disease management tool in wildlife.
AB  - Contraception offers potential as a tool for managing certain diseases in
      wildlife, most notably venereally transmitted diseases or diseases transmitted at
      parturition. Brucellosis is an excellent example of an infectious disease present
      in wild populations that could potentially be managed through
      immunocontraception. Previous studies in bison (Bison bison) suggest that a
      single injection of GonaCon (National Wildlife Research Center, U.S. Department
      of Agriculture/Animal and Plant Health Inspection Service/Wildlife Services, Fort
      Collins, Colorado 80521, USA) results in 3 or more yr of infertility. Ongoing
      studies will determine if the use of GonaCon in bison decreases shedding of
      Brucella abortus from infected animals and will better define the duration of
      infertility following a single injection

PMID- 24437095
TI  - Long-term methods and effects of remotely treating wildlife with
      immunocontraception.
AB  - The development of sophisticated delivery equipment, as well as safer and more
      effective drugs, has made remote delivery of animal drugs a standard and readily
      available tool for wildlife professionals, veterinarians, ranchers, and animal
      control officers. In the 1980s, researchers began treating a wide variety of
      wildlife with injectable porcine zona pellucida immunocontraceptive vaccines.
      Remote delivery of immunocontraceptives has been proven effective at the
      individual and population level for wild horses and urban deer. However, it took
      only a short time at each study site to understand that each time an animal was
      treated with remotely delivered darts, it became more difficult to re-treat;
      researchers were required to adjust to the increased wariness of their targets.
      Multiyear vaccines will not reduce the need for researchers who can adapt to the
      many challenges of applying these nonlethal methods of population control in the
      field. Training, experience, and persistence are required for field personnel to
      adapt and develop new techniques for continued retreatment of previously treated
      free-ranging animals.

PMID- 24437096
TI  - Seventh International Conference on Fertility Control for Wildlife.

PMID- 24437097
TI  - [The profession must take responsibility for continuing education].

PMID- 24437098
TI  - [Suicide attempts are more common among young people with psychotic symptoms].

PMID- 24437099
TI  - [Self-administered remifentanil during labor. Satisfied mothers despite moderate
      pain relief, as shown in quality assurance project].

PMID- 24437100
TI  - [Unexpectedly few findings of tuberculosis in foreign-born pregnant women.
      Results of screening in northeastern Skane].

PMID- 24437101
TI  - [Supragastric belching--severe handicap that can be treated].

PMID- 24437102
TI  - [Structural brain imaging may improve diagnostics in dementia].

PMID- 24437103
TI  - [Drug dosage should be based on renal function].

PMID- 24437104
TI  - [Follow the dosage instructions when the dose is to be adjusted for renal
      function].

PMID- 24437105
TI  - [It is better use a modern formula than being formal].

PMID- 24437106
TI  - [Proton pump inhibitors can cause urticaria].

PMID- 24437107
TI  - [What is the cost of health inequalities?].

PMID- 24437108
TI  - [Estimation of renal function in Children--use the Schwartz formula].

PMID- 24437109
TI  - [Creatinine values should be complemented with GFR estimates].

PMID- 24437110
TI  - [Reply on compensation for egg donation: Two year trial--will be evaluated].

PMID- 24437111
TI  - [The increase should have been preceded by an ethical analysis].

PMID- 24437112
TI  - [A relative's encounter with psychiatric services].

PMID- 24437113
TI  - [Current report from emergency service in South Africa].

PMID- 24437114
TI  - [What is in the abdomen? Ingested foreign body].

PMID- 24437115
TI  - [Physician colleague, how are you dealing with your illness? (interview by Dr.
      med. Bernhard Maulen)].

PMID- 24437116
TI  - [General practice geriatric and palliative care services reimbursed separately].

PMID- 24437117
TI  - [Will the reference point value in EBM be raised by 10 cents?].

PMID- 24437118
TI  - [Does the new general practice EMB come as a surprise attack?].

PMID- 24437119
TI  - [Where do general practitioners have the highest earnings?].

PMID- 24437120
TI  - [After stroke and other brain lesions. Options in aphasia].

PMID- 24437121
TI  - [Variable symptoms, nonspecific findings. Myocarditis: a hard nut for the
      diagnostician].

PMID- 24437122
TI  - [Naturopathy consultation. Heart failure].

PMID- 24437123
TI  - [Bariatric surgery is booming. The general practitioner has a role in after
      care].

PMID- 24437124
TI  - [Patient with excessive sweating. What is really effective in hyperhidrosis?].

PMID- 24437125
TI  - [New general practice EBM. For many general practitioners it is the end].

PMID- 24437126
TI  - [Skin cancer screening. Of course it is worthwhile].

PMID- 24437127
TI  - [Suspected posttraumatic stress disorder. Important symptoms: chronic headache
      and nightmares (interview by Dr. Christine Starostzik)].

PMID- 24437128
TI  - [Coronary heart disease prevention: acquittal for the breakfast egg].

PMID- 24437129
TI  - [Whiplash syndrome: whatever one does ...].

PMID- 24437130
TI  - [Herpes zoster tongue].

PMID- 24437131
TI  - [Worm-induced blockage].

PMID- 24437132
TI  - [Does serum ferritin indicate the severity of non-alcoholic fatty liver?].

PMID- 24437133
TI  - [HPV vaccine does not promote recklessness].

PMID- 24437134
TI  - [Palatal ulcer in anorexia].

PMID- 24437135
TI  - [May patients with pulmonary hypertension fly?].

PMID- 24437136
TI  - [Neurology and psychiatry in the family doctor's office].

PMID- 24437137
TI  - [Treatment of depression by the general practitioner].

PMID- 24437138
TI  - [Pharmacotherapy of Parkinson's disease].

PMID- 24437139
TI  - [Tai Chi Chuan improves balance and gait in people with Parkinson's disease].

PMID- 24437140
TI  - [New anticoagulants in patients with atrial fibrillation].

PMID- 24437141
TI  - [Pharmacological and non-pharmacological treatment of Alzheimer's dementia].

PMID- 24437142
TI  - [New treatment options for alcohol dependence].

PMID- 24437143
TI  - [High-dose zolpidem dependence].

PMID- 24437144
TI  - [Restless legs syndrome: clinical diagnosis].

PMID- 24437145
TI  - [Your diabetic patient wants to exercise].

PMID- 24437146
TI  - [Pressure sore treatment - an interdisciplinary approach].

PMID- 24437147
TI  - [The role of compensatory mechanisms in pathogenesis of coronary heart disease].
AB  - The multilevel system regulating cardiac activity during coronary heart disease
      is considered.

PMID- 24437148
TI  - [Modern approaches to diagnostics and treatment of chronic pancreatitis].
AB  - This review expounds modern views of diagnostic and treatment of chronic
      hepatitis (CH). Diagnosis of CH is possible only by precise methods of non
      invasive morphological study, such as multispiral CT and/or endoscopic
      ultrasonography. Severe pain syndrome in CH requires the use of analgesics,
      pancreatin, tricyclic antidepressants, and anti-oxidant vitamin-mineral
      complexes. Low effectiveness of such therapy is an indication for surgical and
      endoscopic treatment.

PMID- 24437149
TI  - [Certain aspects of therapy of acute hepatic insufficiency].
AB  - The author analysed and summarized available information on acute hepatic
      insufficiency (AHI) with reference to its diagnostics and treatment. The
      principal cause of AHI is hepatitis and alcohol-induced lesions in the liver, the
      main pathogenetic mechanisms are hepatocyte necrosis, apoptosis, and
      necrapoptosis, clinical manifestations include jaundice, coagulopathy and hepatic
      encephalopathy. Special emphasis is laid on the role of cytokines. Liver
      transplantation is the sole radical method for the treatment of AHI despite a
      variety of other therapeutic modalities. Positive effect of efferent and
      gravitational treatment is confirmed Survival in AHI depends on the regenerative
      potential of the liver. Prognosis of AHI is individual even though many scales
      and criteria were proposed.

PMID- 24437150
TI  - [The role of growth factors in pathogenesis of hepatic lesions in patients with
      metabolic syndrome and chronic non-calculous cholecystitis].
AB  - Clinical examination and biochemical studies revealed hepatic functional
      disorders in 30 (93.75 +/- 4.28%) of 32 patients with metabolic syndrome (MS) and
      chronic non-calculous cholecystitis (NCC) and only in 3 (13.63 +/- 7.32%) of 22
      patients with CC without MS. Most patients with CC and MS had elevated levels of
      fibroblast growth factor (FGF) and endothelial growth factor (EGF) suggesting
      activation of fibrotic processes. They were not significantly different from
      normal values in patients with CC without MS. Pair correlation analysis revealed
      the relationship between enhanced activity of the pathological process in the
      hepatobiliary system and increased FGF and EGS levels. It was confirmed by direct
      correlation between FGF. EGS levels and ALT, AST activities. Also, FGF and EGS
      levels were related to leptin and triglyceride levels as well as to HOMA-IR
      index.

PMID- 24437151
TI  - [The influence of depression on the risk of acute cardiovascular diseases in
      women].
AB  - The aim of the work was to elucidate the relation of depression to the awareness
      of and attitude to health as well as effect of depression on the risk of acute
      cardiovascular diseases in women aged 25-64 yr during 16 years. A random
      representative sample of 870 women residing in Novosibirsk was examined in the
      framework of MONICA-psychosocial program (WHO) in 1994. The MOPSY test was used
      for the purpose. All new cases of myocardial infarction and stroke were recorded.
      The prevalence of depression was estimated at 55.2%. Positive self-evaluation of
      health decreased as severity of depression increased. Almost 100% of the patients
      with this condition complained of poor health and were dissatisfied with the care
      given to improve it. Severe depression is associated with stress experienced at
      the workplace and in the family; such women rarely keep to the diet and make
      physical exercises. The relative risk of myocardial infarction and stroke in
      depressed women during 16 years was 2.53 (p < 0.05) and 4.63 (p < 0.05) higher
      respectively than in the absence of depression.

PMID- 24437152
TI  - [Hematological disturbances in subclinical hypothyroidism and their dynamics
      during substitution therapy].
AB  - The aim of the study was to estimate dynamics of hematological disturbances in
      autoimmune thyroiditis and subclinical hypothyroidism (SH) during substitution
      therapy and without it and to elucidate factors promoting successful correction.
      The control group included 36 women, 60 others had SH. They were matched for age,
      BMI, free T3 level but differed in TSH (1.8 +/- 0.81 vs 7.0 +/- 3.41 mcunits/ml,
      p < 0.001) and T4 (p < 0.001) levels. 53 women with SH were followed up for 1
      year; 18 of them were not treated (subgroup A) while 35 were given levothyroxin
      (subgroup B). The following red blood parameters were measured hemoglobin (Hb),
      ferritin, mean erythrocyte volume, erythrocyte Hb content and concentration,
      blood iron (Fe) level. SH was characterized by decreased (compared with control)
      Hb levels (125.8 +/- 13.75 and 133.2 +/- 9.12 g/l, p = 0.005), erythrocyte volume
      (p = 0.022), Hb content per erythrocyte (p = 0.001), ferritin (24.6 +/- 20.56 vs
      36.6 +/- 30.66 mcg/l, p = 0.02), and Fe (p = 0.001). The frequency of anemia
      (28.3 vs 11.1%, p = 0.039) especially microcytic anemia (p = 0.035) increased A
      year later women of subgroup A showed further decrease in ferritin level (p =
      0.011) and increase in anemia frequency (p = 0.016): microcytic (p = 0.23) and
      normocytic (p = 0.015). In subgroup B, the frequency of anemia decreased (p =
      0.001) while ferritin, Fe and Hb levels slightly increased (p > 0.05). The best
      effect of therapy and highest rise in ferritin level were documented in younger
      patients (p = 0.06), in the absence of obesity (p = 0.003) and at the low initial
      ferritin level (p < 0.001). In regression analysis, ferritin level (094 [0.89;
      0.99], p = 0.035) proved the most significant predictor of therapeutic
      effectiveness. SH was characterized by Fe deficiency, tendency to microcytosis
      and anemia that progressed in the absence of therapy. Substitution therapy
      promotes normalization of hematological problems especially in young and non
      obese patients. Sideropenic syndrome suggests potential benefits of levothyroxin
      therapy and may be regarded as an additional indication for its prescription.

PMID- 24437153
TI  - [Quality of life and problems posed by hypoglycemia in type 2 diabetes mellitus
      during oral hypoglycemic therapy].
AB  - Quality of life characteristics, hypoglycemic episodes and patients' attitude
      toward them were estimated in the patients with type 2 diabetes mellitus based on
      the modern recommendations for the patient-oriented treatment with metformin in
      combination with sulfonylurea derivatives (M+S) therapy, traditional approach, n
      = 83) and metformin in combination with vildagliptin (M+V therapy, innovative
      approach, n = 111). M+V therapy ensured a higher quality of life than M+S therapy
      based on all SF-36 scales. Quality of life parameters corresponded to population
      norms in most patients given M+V therapy and only in 52% of those treated with
      M+S. The frequency of hypoglycemic episodes, related concerns, and other problems
      associated with this condition were less apparent in case of M+V therapy.
      Transition from M+S to M+V therapy resulted in the improvement of quality of life
      and reduction in the frequency of hypoglycemia. Quality of life did not change
      after transition to M+S therapy while the frequency of hypoglycemia and the
      number of related problems increased. HbA1c levels were similar in both groups
      (0.8% difference). According to patients' reports M+V therapy is more efficient
      than M+S; these data allow to comprehensively evaluate the efficacy of therapy
      and monitor the health state of diabetic patients in the course of treatment.

PMID- 24437154
TI  - [Diurnal food intake rhythm and gustatory sensitivity in patients with obesity
      and dyspepsia].
AB  - Disordered eating behavior, nutritional regime, and food habits lead to
      deterioration of quality of life especially in patients with digestive problems.
      The role of nutrition in etiology and pathogenesis of dyspepsia is currently the
      subject of increasing research interest that extends to gustatory sensitivity,
      diurnal nutritional rhythms, and psychological characteristic of the patients
      with dyspeptic syndrome and obesity This study included 68 patients (42 women and
      26 men) aged 20-60 (mean 46.2 +/- 4.6) years with dyspeptic syndrome and 26
      practically healthy subjects (1st control). Study group 1 included 28 patients
      with dyspepsia and normal BMI, group 2 was comprised of 40 dyspeptic patients
      with obesity. Disordered diurnal nutritional rhythms and food intake regime were
      documented in 24 (86%) and 36 (90%) patients of study groups 1 and 2 respectively
      compared with 10 (50%) in the 1st control group. Gustatory thresholds were
      changed in 21 (75%) and 38 (95%) patients of study groups 1 and 2. These data
      suggest that changes in diurnal nutritional rhythm and gustatory sensitivity are
      related to eating preferences and can play a role in pathogenesis of obesity and
      dyspepsia. It implies the necessity of their correction by relevant therapeutic
      and preventive treatments.

PMID- 24437155
TI  - [Peculiarities of diagnostics of hyperplastic processes in endometrium during
      long postmenopause].
AB  - Comparative characteristics of hyperplastic processes are presented based on the
      results of ultrasound and postoperative histological studies. The informative
      value of ultrasound diagnostics of hyperplastic processes in endometrium during
      long postmenopause was estimated at 60%. Up to 40% of such diagnoses were not
      confirmed by histological studies of the material obtained by differential
      curettage of cervical canal and uterine walls. No evidence of the influence of
      human factor (diagnostic error) was obtained.

PMID- 24437156
TI  - [Prognostication of the probability of ischemic stroke].
AB  - The study included 405 patients with ischemic stroke and 35 ones with transitory
      ischemic attack. Predictors of stroke are considered and approaches to its
      prognostication proposed The results can be used to distinguish patients in need
      of preventive therapy of ischemic stroke.

PMID- 24437157
TI  - [Goals and possibilities of therapeutic rehabilitation of oncological patients].
AB  - Various manifestations of oncological diseases encountered in the practical work
      of a therapist are discussed. They are related to both the clinical course of the
      diseases and their treatment. Characteristics of somatic disorders genesis of
      which is determined by the active or treated tumour are presented. The necessity
      of observation of oncological patients at all stages of cancer treatment and
      after its termination is emphasized. Goals and forms of oncological
      rehabilitation are described.

PMID- 24437158
TI  - [Autoimmune hepatitis].
AB  - Autoimmune hepatitis (AH) is a chronic inflammatory immunodependent disease of
      the liver. Women are affected more frequently than men. The patients show
      clinical and morphological signs of chronic hepatitis, extrahepatic
      manifestations of immune disorders (autoimmune thyroiditis, non-specific
      ulcerative colitis, vitiligo, diabetes mellitus, etc.), readily respond to
      glucocorticoid therapy have elevated levels of ALA, gamma-globulins (especially
      IgG), serum ANA, SMA, LKM or SLA antibodies. Untreated AH promotes rapid
      development of liver cirrhosis with 90% 10-year lethality. AH is diagnosed by
      exclusion and is of primary importance for clinical practice. The treatment is
      based on the use of immunosuppressors as a rule prescribed in addition to steroid
      therapy. It results in complete remission and normal life expectancy in 80% of
      the cases.

PMID- 24437159
TI  - [Therapeutic strategy for diffuse toxic goiter].
AB  - The methods for the treatment of diffuse toxic goiter (Graves'disease) are
      considered including analysis of 71 domestic and foreign publications with
      special reference to debatable and unresolved problems. The goals of and main
      indications for the treatment, the relevant surgical techniques, and possible
      complications are discussed. Comparative characteristics of the methods for the
      management of diffuse toxic goiter are reviewed.

PMID- 24437160
TI  - [The use of remaxol in combined intensive therapy of acute mushroom poisoning].
AB  - A case of very severe mushroom poisoning is reported. Traditional
      hepatoprotective therapy with ademethionine, ornithine-aspartate, and essential
      phospholipids failed to ensure positive dynamics of the hepatic and general
      functional state. Hepatic insufficiency was complicated by cerebral oedema and
      swelling, bilateral pneumonia, and acute respiratory distress of mixed genesis.
      Combined therapy with remaxol and ornithine aspartate produced beneficial effect,
      resulted in the improvement of the patient's condition and favorable outcome of
      the life-threatening intoxication.

PMID- 24437161
TI  - [Saint Olga Moscow Children's Hospital].

PMID- 24437162
TI  - [Rheumatic fever].
AB  - This lecture-style paper highlights all major problems pertinent to rheumatic
      fever Definition of acute RF and chronic rheumatic heart disease is proposed and
      desirability of the use of these terms in clinical practice is explained. Present
      day epidemiology of RF is described with reference to marked differences in its
      prevalence in developed and developing countries. Modern classification of acute
      RF is described as adopted by the Russian Association of Rheumatologists and
      recommended for the use in Russian medical facilities. Discussion of etiological
      issues is focused on such virulence factors as beta-hemolytic streptococcus A and
      genetic predisposition confirming hereditary nature of RE Its clinical features
      are described along with laboratory and instrumental methods applied for its
      diagnostics. Large and small diagnostic criteria of RF are considered. Special
      attention is given to the treatment of RF and its complications (antibiotic,
      pathogenetic, and drug therapy). Its primary and secondary prophylaxis is
      discussed in detail, preparations for the purpose are listed (with doses and
      duration of application). In conclusion, criteria for the efficacy of therapy are
      presented along with indications for hospitalization and emergency treatment.

PMID- 24437163
TI  - [Evolution of surgical and endonasal methods for correction of main-stem venous
      reflux in patients with primary varicosis of the lower extremities].
AB  - Adequate high-quality diagnostics of primary varicosis of the lower extremities
      is a challenging problem bearing in mind its high prevalence and social
      significance. This review focuses on historical aspects of the problem and
      current views of domestic and foreign specialists. Special attention is given to
      the treatment of main-stem venous reflux as a principal pathogenetic mechanisms
      of progressive venous insufficiency. The history of development and improvement
      of surgical methods for the treatment of the disease, from traumatic to minimally
      invasive outpatient interventions is expounded with the emphasis on modern
      endovasal techniques for correction of pathological venous reflux (radiofrequency
      obliteration and laser coagulation). The important role of
      phleboscleroobliteration in the treatment of primary varicosis is underscored. It
      is maintained that sclerotherapy remains an accessible effective method for the
      correction of varicose disease. Intraoperative catheter stem scleroobliteration
      of the main vessels yields good results provided the main principles of surgical
      intervention are met. Some unresolved problems include the choice of more
      informative indications for the treatment of primary varicosis of the lower
      extremities on an individual basis.

PMID- 24437164
TI  - [Anti-inflammatory potential of melatonin].
AB  - The summary of anti-inflammatory properties, cellular and systemic mechanisms of
      action of epiphyseal melatonin is presented. Dual effect of interaction between
      melatonin and non-steroidal anti-inflammatory agents is discussed with reference
      to enhancement of their specific activity and prevention of side effects.

PMID- 24437165
TI  - [Manifestations of polymorphism of beta1-adrenoreceptors in patients with newly
      diagnosed cardiac rhythm disorders].
AB  - Individual peculiarities of the receptor apparatus of cardiomyocytes may
      determine pathological features of heart activity and susceptibility to
      pharmaceuticals. The possible role of beta-adrenoreceptor polymorphism in the
      development of cardiac rhythm disturbances is assessed by PCR. Special attention
      is given to A145G polymorphism of the ADRB1 gene in 127 patients with primary
      cardiac rhythm disorders. It was shown that AJ45G polymorphism (Ser49Gly) at DNA
      sites encoding for the amino acid sequence of beta-1 adrenoreceptors can
      influence the development of sex-specific cardiac rhythm disorders.

PMID- 24437166
TI  - [Auricular vagal stimulation in the treatment of patients with left ventricular
      dysfunction].
AB  - We assessed effect of enhancement of parasympathetic activity by indirect vagal
      stimulation via sensitive n. vagus-r. auricularis terminals on dynamics of
      clinical conditions, ejection fraction and global longitudinal left ventricle
      deformation in patients with chronic cardiac insufficiency (CCI). This
      comparative placebo-controlled parallel study 3 months in duration included 70
      patients with chronic coronary heart disease, signs of IIl-IV FC CCI, and sinus
      rhythm. Auricular electric vagal stimulation (AEVS) was performed using a device
      for electric stimulation of sensitive vagus terminals (patent No 2327492 of
      27.06.2008). The complex of clinical and instrumental studies included 6 min walk
      test, echocardiography, and speckle tracking imaging before, immediately and 3
      months after AEVS. A course of AEVS improved clinical conditions in 58 (92.06%)
      of the 63 patients due to one-grade or greater decrease of CCI FC and increase of
      the walking distance. This effect persisted till month 3. It was absent in 5
      (8.33%) patients. Improvement of clinical conditions with the decrease of CCI FC
      was accompanied by increase of left ventricular ejection fraction due to
      diminished end-systolic volume. The ejection fraction did not change in 4
      patients with HR over 80/min. All patients with lowered HR after AEVS showed
      improved LV contractility in the longitudinal direction.

PMID- 24437167
TI  - [Autonomous pharmacodynamics of organic nitrates in patients with unstable
      angina].
AB  - The pharmacological test with the use of high-resolution rhythmocardiography for
      the analysis of cardiac rhythm variability associated with peripheral vegetative
      regulation of the synoatrial node was applied to study effects of a single dose
      of organic nitrates (nitroglycerin and mononitrate isosorbide) in 41 patients
      with unstable angina. Rhythmocardiograms were obtained before and after a morning
      sublingual dose of nitrates preceding intake of basal drugs. The results suggest
      negative action of nitrates on peripheral vegetative regulation of pacemaker
      activity of the synoatrial node.

PMID- 24437168
TI  - [ANCA-associated vasculitis affecting lungs and kidneys: clinical and
      morphological characteristic, treatment, outcomes].
AB  - Up to 80% of all cases of pulmonary-renal syndrome are due to systemic vasculitis
      associated with antibodies to neutrophil cytoplasm (ANCA). Most patients die
      within the first year after the onset of the disease but adequate
      immunosuppressive therapy ensures the 5-year survival rate of 65-75%. We obtained
      clinical and morphological data for 34 patients with ANCA-associated vasculitis
      affecting lungs and kidneys treated at S. P. Botkin Hospital in 1994-2012. 16
      patients presented with granulomatous polyangiitis (Wegener 's granulomatosis),
      11 with microscopic polyangiitis, and 7 with eosinophilicpolyangiitis (Churg
      Strauss syndrome). We made the definitive diagnosis in 79% of the cases.
      Pulmonary lesions were largely in the form offocal, nodular and infiltrative
      changes, one third of the patients suffered blood spitting/pulmonary hemorrhage
      and 15% respiratory distress. Most patients had renal dysfunction (16% required
      emergency hemodialysis), lesions of ENT skin, joints, peripheral nervous system,
      and eyes. Therapy with corticosteroids and cytostatics increased the total and
      renal survival rate up to 91 and 82% respectively despite unfavourable prognostic
      factors in most patients. Duration of observation was 32.5 [0.1;129] months, the
      survival rate depended on the severity of lung lesions whereas renal problems had
      no appreciable effect on life prognosis.

PMID- 24437169
TI  - [24-hour monitoring central aortic pressure in patients with hypertensive disease
      and concomitant chronic obstructive pulmonary disease].
AB  - A total of 58 patients with essential hypertension were examined. 27 of them had
      a combination of essential hypertension and chronic obstructive pulmonary disease
      (COPD), 31 persons had isolated essential hypertension. The control group
      included 13 healthy individuals. The daily monitoring of blood pressure with a
      BPLab apparatus and the analysis of peripheral and central aortic pressure were
      performed. Comparison of groups was carried out using the Mann-Whitney test. The
      combination of hypertension and COPD was associated with increased daily and
      average daily peripheral and central aortic pressure compared with isolated
      essential hypertension and the control group. During daily monitoring of
      peripheral blood pressure the "dipper" type predominated in patients with
      isolated essential hypertension (41, 95%) and "non-dipper" type in those with
      comorbid disorders (44, 44%). The analysis of nocturnal blood pressure reduction
      in the aorta in patients with essential hypertension and COPD revealed the
      increased frequency of "non-dipper" type (55, 55%). The analysis of the central
      aortic pressure in patients with isolated essential hypertension showed the
      decreased incidence of "dipper" type (21, 87%). It is concluded that daily
      monitoring of the central aortic pressure permits to identify abnormal profiles
      with a higher frequency than the study of peripheral blood pressure.

PMID- 24437170
TI  - [Complicated form of A/HINI (2009) influenza in pregnant women].
AB  - We undertook prospective and retrospective analysis of 120 cases of A/HINI (2009)
      influenza complicated by pneumonia in pregnant women with the purpose of
      comprehensive assessment of these conditions taking into account relevant risk
      factors and preventive measures. Control groups were comprised of 100 pregnant
      women with uncomplicated influenza and 100 ones who did not fall ill during flu
      pandemic. The risk of severe disease and probability of its fatal outcome in
      pregnant women were 2.5 and 2.4 times those in the general population. Most women
      developed pneumonia in the 3d trimester Risk factors offlu complications included
      smoking, obesity, underlying respiratory and cardiovascular diseases, sexually
      transmitted infections. Combined prophylaxis reduced probability of pandemic
      influenza in pregnant women by 5.6-7 times. Severe forms of the disease were due
      to manifest symptoms of intoxication and concomitant pneumonia. The clinical
      picture of lethal cases was characterized by severe pneumonia with subtotal lung
      involvement, rapid progress of acute respiratory distress syndrome, and
      development of polyorgan insufficiency.

PMID- 24437171
TI  - [Melatonin secretion in women of advanced reproductive age].
AB  - The patient's age is a key factor determining success of in vitro fertilization.
      The ovarian reserve and oocyte quality are known to decrease with age. Much
      attention has been given recently to the role of epiphysis and its hormone,
      melatonin, in synchronization of daily and seasonal biorhythms in anti-stress
      protection and neuroregulation of reproductive processes. The aim of our work was
      to study melatonin levels in infertile women of reproductive age. We also
      measured sex hormones, anti-Mullerian hormone, FSH, and LH in blood and melatonin
      sulfate in urine at 8 points (RIA). Women of advanced reproductive age showed
      markedly reduced melatonin secretion due to functional disorders in the
      hypothalamic-pituitary-gonadal axis. Results of the study suggest the necessity
      of prescription of exogenous melatonin to the patients included in assisted
      reproduction programs for the improvement of their efficacy.

PMID- 24437172
TI  - [Comparative efficacy of infliximab and adalimumab in patients with rheumatoid
      arthritis].
AB  - We compared the efficacy of recombinant infliximab and adalimumab in patients
      with severe and moderately severe rheumatoid arthritis. Infliximab produced rapid
      anti-inflammatory effect in the early period of therapy whereas adalimumab
      ensured more stable reduction of clinical and laboratory parameters of activity.

PMID- 24437173
TI  - [Diagnostic difficulties in patients with disseminated processes in lungs].
AB  - Pulmonary disseminations are frequently encountered in the practical work of a
      multi-disciplinary hospital and require differential diagnostics by join efforts
      of specialists in different fields of medicine. The aim of this study was to
      estimate the frequency and clinical picture of these conditions. We analysed
      clinical records of 154 patients admitted to the department of pulmonology and
      intensive therapy. Most patients in need of intensive therapy (n=54) presented
      with disseminations of infectious origin, such as disseminated tuberculosis
      (32%), pulmonary problems associated with sepsis and infectious endocarditis
      (14%), HIV-associated disseminations (23%). Canceromatosis and idiopathic
      interstitial pneumonia occurred in 18 and 13% of the cases respectively. Patients
      in the department of pulmonology had pulmonary dissemination syndrome of unclear
      origin or no overt clinical symptoms (n=100). The leading cause of their disease
      was sarcoidosis (60%) and idiopathic interstitial pneumonia (20%). 27 patients
      had this syndrome associated with HIV/AIDS. Clinical examples and difficulties of
      early diagnostics of pulmonary dissemination syndrome are discussed with
      reference to underlying diseases (sepsis, infectious endocarditis, HIV/AIDS,
      Goodpasture's syndrome). Special attention is given to the management of this
      condition based at a multidisciplinary hospital.

PMID- 24437174
TI  - [Prehospital stage of medical aid to patients with acute coronary syndrome and
      elevated ST segment].
AB  - We studied effect of time on the outcome of acute coronary syndrome and elevated
      ST segment at the prehospital stage. Logistic regression analysis revealed two
      time-dependent predictors: "symptom-needle" time and total call service time. In
      patients undergoing prehospital thrombolysis, these indices (88 and 85 min
      respectively) reliably predicted the probability of fatal outcome. Their values
      of 71 and 77 min respectively predicted the risk of unfavourable outcome. The
      total call service time may serve as an indicator of the quality of work of an
      ambulance crew at the prehospital stage of management of acute coronary syndrome
      with elevated ST segment.

PMID- 24437175
TI  - [Injuries to myocardium in infectious endocarditis].
AB  - Clinical and morphological characteristics of myocardium in infectious
      endocarditis (IE) are described as exemplified by pathological changes in the
      vascular bed, stroma, and myofibrils. Multiple sclerotic changes in myocardium in
      the form of "sheath sclerosis" were revealed. It is shown that progress of
      cardiac insufficiency in IE may be due to specific changes in the heart muscle.
      The necessity of early diagnostics of myocardial lesions is discussed with
      reference to revision of antibiotic therapy and modern surgical treatment of lE.

PMID- 24437176
TI  - [The problem of pharmaceutical adulteration and attempts of its solution in
      Russia in the late XIXth-early XXth centuries].

PMID- 24437177
TI  - [Clinical significance of Helicobacter pylori infection].
AB  - This article deals with modern concepts of H. pylori infection and its role in
      the development of gastric and extragastic pathology. The currently available
      algorithms of diagnostics and treatment of this infection are presented
      Recommendations of recent Maastricht consensuses (7MC-3, 2005; MC-4, 2010) on
      diagnostics and treatment of H. pylori infection are considered. The data on
      resistance of H .pylori to antibiotics, mechanisms of its development and methods
      of control are summarized.

PMID- 24437178
TI  - [Has the discovery of Helicobacter pylori actually made a revolution in
      gastroenterology?].
AB  - Part 1 of this paper presents a brief description of the results of 25 year
      investigations of H. pylori infection and its contribution to the development of
      gastroduodenal pathology (chronic hepatitis, ulcer disease, stomach cancer,
      gastric maltoma) with reference to its diagnostics, strategy and efficacy of
      eradication therapy. Part 2 contains arguments and facts that contradict opinions
      in favour of the leading role of H. pylori infection in pathogenesis of major
      gastro-duodenal disorders as well as results of the studies of normal and
      anomalous gastric mucosal microflora comprising numerous bacteria, besides H.
      pylori, exhibiting such properties as adhesiveness, invasiveness (unlike H.
      pylori), virulence, and urease activity. The causes behind the failure of
      eradication therapy are discussed with reference to the decrease of its
      effectiveness to the critical level attributable largely to misjudgements of the
      authors of Maastricht recommendations.

PMID- 24437179
TI  - [The influence of ITGB3 gene polymorphism on the frequency of arterial
      hypertension in patients with acute coronary syndrome].
AB  - PLA polymorphism of platelet integrin receptor, GpIIIa glycoprotein, (PLA
      polymorphism of the ITGB3 gene) is associated with the risk of myocardial
      infarction and CHD especially in young subjects. We analyzed ITGB3 gene
      polymorphism in patients with acute coronary insufficiency. It was shown that
      increased AP and altered blood lipid spectrum in the acute period of disease in
      carriers of the PLA allele (PLA1/PLA2 and PLA2/PLA2 genotypes) can be regarded as
      manifestations of stress reaction. The data obtained indicate that the PLA2
      allele is a predictor of complications of acute coronary insufficiency. This
      observation is of importance for the choice of adequate therapy for the patients
      with this disorder.

PMID- 24437180
TI  - [Autonomous cardioneuropathy in patients with coronary heart disease].
AB  - This paper reports the results of an electron microscopic study of the sinoatrial
      node in deceased patients with CHD in whom high-resolution rhythmocardiography
      revealed autonomous cardioneuropathy. Non-specific morphological changes in
      pacemaker cells of the sinoatrial node (swelling and disintegration of
      mitochondria, incorporation of calcium and accumulation of lipofuscin in
      mitochondria) can be regarded as manifestations of ischemic insufficiency of
      cardiac tissue perfusion. The rhythmocardiograms of such patients showed signs of
      autonomous cardioneuropathy manifest as the sharply decreased amplitude of all
      vegetative waves. The spectral power pattern was dominated by inefficient humoral
      metabolic regulation due to suppression of protective parasympathetic regulation.

PMID- 24437181
TI  - [Resistance to clopidogrel and polymorphism of P2RY12 and GPIIIA genes in
      patients with chronic coronary heart disease].
AB  - We studied the association between clopidogrel resistance, H1/NH2 polymorphism of
      the P2RY12 gene and T156C polymorphism of the GpIIIa gene in residents of Western
      Siberia suffering chronic CHD. It was shown that the occurrence of H1 and H2
      haplotypes of the P2RY12 gene and 1565T and 1565C alleles of the GpIIIa gene was
      similar to that reported for European populations. Patients showing variable
      platelet response to the inhibitory action of clopidogrel were not significantly
      different in terms of P2RY12 and GpIIIa genotype distribution. To conclude, the
      study revealed no association between the risk of clopidogrel resistance and the
      presence of polymorphic variants of platelet receptor genes P2RY12 and GpIIIa.

PMID- 24437182
TI  - [Phase analysis of the cardiac cycle in patients with arterial hypertension based
      on the results of equilibrium radioventriculography].
AB  - AIM: To study cardiac cycle parameters in patients with grade I and II AH by
      equilibrium radioventriculography (ERVG) and the possibility of using them for
      diagnostics of systolic and diastolic myocardial dysfunction. MATERIALS AND
      METHODS: Left and right ventricular diastolic and systolic functions were
      evaluated by conventional ERVG using a MB-9100 gamma-chamber (Gamma, Hungary) and
      the Gold-Rada+ system for data collection and processing. The study involved 142
      patients divided into 3 groups. Group 1 included 38 patient with grade 1 AH (mean
      age 20.7 +/- 6.2 yr), group 2 85 patients with grade II AH (58.7 +/- 10.7 yr),
      group 3 19 practically healthy subjects (29.4 +/- 10.8 yr). RESULTS: No
      significant abnormalities in hemodynamic characteristics except increased filling
      of the right ventricle for 1/3 diastole were observed in group 1. Decreased
      filling for 1/3 diastole, maximum filling rate, and the ratio of filling to
      ejection rates were revealed in group 2. In order to counterbalance HR
      differences, the time-related ERVG values were calculated per RR interval; it
      allowed to reveal diastolic disorders confirmed in the study of ERVG
      "hemodynamics characteristics. Patients with grade II AH showed a longer time of
      maximum filling rate with respect to left and right ventricular RR intervals
      compared with controls. In group 1, this parameter was lower than in healthy
      subjects.

PMID- 24437183
TI  - [Alterations in the clinical course of hypertensive disease during the last 25
      years].
AB  - We undertook analysis of 234 case histories of the patients with HD dated 1985
      1987 (group 1) and 2010-2012 (group 2). It showed differences in clinical
      manifestations of HD between the two periods. First, "cerebral" complaints were
      less frequent in group 2 while functional state of the cardiovascular system
      (tolerance of physical load) and efficacy of hypotensive therapy improved.
      Second, decreased AP did not exclude progression of atherosclerosis and its
      complications in the presence of other risk factors. MS components (increased
      body mass, dyslipidemia, hyperglycemia) were more common in group 2 which
      suggests the necessity of combined prophylaxis of cardiovascular catastrophes.
      Third, changes in daily AP profile in group 2 require more extensive use of 24 hr
      AP monitoring for the choice of hypotensive therapy and estimation of its
      efficacy at specified time. Fourth, modern methods for the treatment of AH slow
      down the development of renal symptoms of AH.

PMID- 24437184
TI  - [Long-term prospective observation of patients with hypertrophic cardiomyopathy].
AB  - This paper summarizes results of a long-term prospective study of the patients
      with hypertrophic cardiomyopathy (GCMP) divided into two groups, one with
      progressive disease (42%) the other with its stable course (58%). The progress of
      GCMP was not associated with thickening of the left ventricle. Predictors of the
      progress included manifest and extensive asymmetry of myocardial hypertrophy.
      Dilatation cardiomyopathy developed in 5.5% of the cases of nonobstructive GCMP.
      Therapy had no significant effect on clinical manifestations of GCMP.

PMID- 24437185
TI  - [Age-related clinical and laboratory features of patients with occluded main
      arteries of lower extremities].
AB  - The study of clinical and laboratory features of patients with occluded main
      arteries of lower extremities included morphological characteristics of
      peripheral blood platelets in patients of different age in the acute period of
      the disease and after surgical treatment. The results were subjected to
      correlation analysis versus standard hemostatic parameters. Mean cell volume and
      enhanced anisocytosis proved the most informative morphological indicators. The
      mean platelet volume was increased in all patients before and after surgery
      especially in the elder age group. It reflected persistent activation of
      thrombocytopoiesis as confirmed by the studies of hemostasis. Therefore, these
      parameters may be used for additional testing in diagnostics of the risk of
      ischemic complications and repeated thrombosis. The timely prescription of
      auxiliary corrective therapy increases effectiveness of the treatment and the
      quality of life in the patients with occluded main arteries of lower extremities.

PMID- 24437186
TI  - [The treatment of patients with broncho-pulmonary pathology and concomitant
      disturbances of oxalic acid metabolism].
AB  - This work was aimed at estimating the role of special therapy of patients with
      bronchial asthma, COPD and hyperoxaluria designed to restrict the delivery or
      eliminate excess of oxalates and producing well apparent beneficial effect
      confirmed by the disappearance or decrease of clinical and functional
      manifestations of obstruction, reduction of requirements for broncholytic and
      anti-inflammatory agents.

PMID- 24437187
TI  - [The role of chronically disordered duodenal patency in the development of post
      gastroresection syndrome].
AB  - We assessed results of examination and treatment of 100 patients with ulcer
      disease who had undergone Bilroth-1 stomach resection. Chronic disorder of
      duodenal patency was revealed in 86% of the patients. This condition was shown to
      play the leading role in the development of post-gastric resection syndrome.
      Reflux-gastritis was associated with damping syndrome in 66.3% of the patients
      and with recurrent ulcer in 8.1%. It is concluded that conservative and surgical
      treatment of post-gastric resection syndrome should be aimed at correction of
      chronic disorders of duodenal patency.

PMID- 24437188
TI  - [Non-invasive methods for the assessment of platelet, leukocyte, erythrocyte
      aggregation and coagulation hemostasis].
AB  - A non-invasive method for the study of platelet aggregation and formation of
      leukocyte-erythrocyte-platelet aggregates as well as certain hemostatic
      parameters is proposed. The method is based on the speckle-analysis of coherent
      light scattering from the surface of erythrocytes moving in an artificially
      isolated vessel segment. It was shown that light scattering index significantly
      correlated with ADP-, adrenalin-, or collagen-induced platelet aggregation, with
      the formation of leukocyte-erythrocyte or platelet-erythrocyte aggregates, and
      with the levels of fibrinogen, soluble fibrin-monomer complexes and related
      parameters. It is concluded that the proposed method for the study of hemostatic
      system can be used to roughly evaluate intensity of intravascular blood
      coagulation and probability of thrombosis.

PMID- 24437189
TI  - [Hyperplastic processes in endometrium of women during prolonged menopause].
AB  - A total of 651 patients were available for observation during prolonged
      menopause. It was shown that fibrous-glandular polyps of endometrium occur much
      more frequently in such women than glandular and glandular-cystic hyperplasia
      (54.37 and 2.91% respectively). Prolonged menopause changes the relationship
      between the causes of hyperplastic processes with decreasing influence of
      hyperestrogenism in combination with disturbances of lipid and carbohydrate
      metabolism (from 60-70 to 6.7%) and increasing atrophy (from 30-40 to 93.3%).
      Ultrasound examination of small pelvis organs is obligatory in these patients
      even if it is fraught with hyperdiagnostics of endometrium pathology.

PMID- 24437190
TI  - [Amiodarone-induced pneumonia].
AB  - A case of cordarone-induced pneumopathy in a man is reported diagnosed one year
      after the appearance of its first symptoms. Withdrawal of cordarone and
      prescription of glucocorticoid therapy resulted in positive dynamics of the
      patient's condition. Differential diagnostics of this rather common pathology
      sometimes encounters difficulties. Demonstration of this complication of anti
      arrhythmic therapy illustrates the importance of careful analysis of the current
      and past medical history of a patient with special reference to the drugs used
      for the treatment.

PMID- 24437191
TI  - [On the paper "Eubiosis and dysbiosis of the gastrointestinal tract" by Ia.S
      Tsimmerman].

PMID- 24437192
TI  - [Pletnev D.D. about the "necessity of joint and simultaneous study of somatic and
      psychic symptoms"].

PMID- 24437193
TI  - [Formation of clinical teaching in Russia (by force of the plan proposed by Mr.
      rector Frank)].

PMID- 24437194
TI  - [Metabolic engineering of yeast Hansenula polymorpha for construction of
      efficient ethanol producers].
AB  - Until recently, the methylotrophic yeast was not considered as a potential
      producer of biofuels, particularly of ethanol from lignocellulosic hydrolysates.
      The first work published 10 years ago reveals the ability of thermotolerant
      methylotrophic yeast Hansenula polymorpha to ferment xylose--one of the main
      sugars of lignocellulosic hydrolysates, which has made these yeast promising
      organism for high temperature alcoholic fermentation. Such feature of the H.
      polymorpha can be used in the implementation of potentially effective process of
      simultaneous saccharification and fermentation (SSF) of raw materials. SSF allows
      combining enzymatic hydrolysis of raw materials with the conversion of produced
      sugars into ethanol: enzymes hydrolyze polysaccharides to monomers, which are
      immediately consumed by microorganisms-producers of ethanol. However, the
      efficiency of alcoholic fermentation of major sugars realized after hydrolysis of
      lignocellulosic raw materials, and especially xylose, by wild strains of H.
      polymorpha requires significant improvement. In this review the main results of
      metabolic engineering of H. polymorpha for the construction of improved producers
      of ethanol from xylose, starch, xylan, and glycerol, as well as strains with
      increased tolerance to high temperature and ethanol are represented.

PMID- 24437195
TI  - [Microbial lipids as a source for biofuel].
AB  - This review presents the main directions and experimental data to search among
      the different species of yeast--active producers of lipids and the ways to
      lipidogenesis process optimization in the most promising stains. It was shown
      that enzymatic processes course can be directed with maintaining the necessary
      cultivation conditions. The influence on the growth, development and biochemical
      activity of microbial medium composition, temperature, aeration and oxidation
      reduction conditions was considered. These factors changing have affected the
      microorganisms biosynthetic activity, lipidogenic yeasts activity and synthesized
      lipids composition. Lipidogenic yeasts ability and relatively rapid ability on
      changing the amount and composition of lipids by the direct cultivation leads to
      the conclusion that lipids obtained by microbial synthesis can be a source of
      commercial raw materials for biofuel.

PMID- 24437196
TI  - [Biodiesel from microalgae: ways of increasing effectiveness of lipids
      accumulation by genetic engineering methods].
AB  - Microalgae are viewed as one of the most perspective producer of lipids for
      biodiesel production. The review shows the results of researches of genes'
      expression increase actually included in fatty acids biosynthesis. The increase
      of effectiveness of solar energy absorption and carbon dioxide fixation
      influences the microalgae productivity. Blocking expression of genes that are
      responsible for starch synthesis, changes the balance towards the quantity growth
      of lipids in the cell. The change of the length in fatty acids carbon backbone
      chain towards its shortening is important in the technology of biodiesel
      production. Operating processes of lipids' catabolism is another way of
      increasing their quantity. And at last using the methods of transcription
      analysis allows us to get deeper into the process of intensive accumulation of
      lipids in stressful conditions for the purpose of directing these processes.

PMID- 24437197
TI  - [Isolation and characterization of lactose-fermenting yeasts Candida kefyr].
AB  - The search for lactose-fermenting yeast strains has been conducted among 162
      strains isolated from various plants and 28 yeast strains isolated from cheese.
      Four yeast strains have been shown to ferment lactose. They have been identified
      as Candida kefyr. Specific beta-galactosidase activity of the studied strains
      grown on lactose-containing medium was 1501-2113 U/g cell. The ethanol production
      by strains C. kefyr C24 and C30 was significantly inhibited by the increase in
      substrate concentration (100 g/l).

PMID- 24437198
TI  - [Alternative type of fuel--biobutanol].
AB  - Butanol--an alternative fuel that on amid dwindling global (accessible) oil
      reserves can serve as a source of energy. In the industrial-scale butanol is
      produced by chemical synthesis, although initially butanol production was due to
      microbiological synthesis. For cost-efficient production, a strain of
      microorganisms must have over production of butanol. In the review of butanol
      synthesis pathway with the help of microorganisms, their regulation, the
      principles and techniques of increasing the productivity of the most promising
      strains and producer strains for industrial production.

PMID- 24437199
TI  - [The influence of application of a low-frequency magnetic field on the serum
      corticosterone level (an experimental study)].
AB  - The results of analysis of the literature publications suggest the necessity of
      experimental studies aimed at investigation of modulating effect of low-frequency
      magnetic fields on endocrine organs. The present study was carried out using 200
      outbred white male rats (body weight 200-220 g). Corticosterone was measured in
      blood sera following the application of a low-frequency magnetic field (20 and 53
      Hz with induction from 0.4 to 6 mT) generated by a Mini-Expert-T apparatus for
      induction magnetic therapy during 30 minutes. It was shown that the application
      of the alternating magnetic field to the adrenal region of the rats in the
      selected frequency and induction ranges caused a significant increase in the
      serum corticosterone levels. The results of the present study on the hormonal
      activity of rat adrenals give reason to consider the influence of the alternating
      magnetic fields as being modulatory. Analysis of the data thus obtained has
      demonstrated the non-linear dependence of glucocorticoid activity of the rat
      adrenal glands on the induction strength of the alternating magnetic field.

PMID- 24437200
TI  - [The influence of drinking mineral water and magnetic field on the development of
      compensatory-adaptive reactions in rat testicles under immobilization stress
      conditions].
AB  - The experiments were carried out on the white male rats using light and electron
      microscopy in combination with biochemical methods. It was shown that the
      combination of consumption of drinking sulfate mineral water (MW) and application
      of a magnetic field following immobilization stress promotes the development of
      compensatory-adaptive processes in the rat testicles to a greater degree than
      drinking mineral water alone. An important contribution to the improvement of
      spermatogenesis comes from the restoration of structural and functional integrity
      of the components performing the barrier function in the testicles.

PMID- 24437201
TI  - [The influence of general infrared sauna on the antioxidant systems in the blood
      of volunteers].
AB  - This comprehensive clinical and laboratory study was designed to elucidate the
      antioxidant status of the volunteers before and after a course of general
      infrared irradiation. It was shown that the effect of high temperatures promotes
      the development of oxidative stress that is followed by the formation of adaptive
      reactions in the form of activation of antioxidant protection, enhancement of non
      specific responses of the cells, increase of stability and restoration of
      structural homeostasis of erythrocyte membranes. The molecular mechanism of
      endothelium-independent vasodilation develops by the end of the treatment period;
      it may serve as the compensatory-adaptive reaction needed to maintain the
      adequate tone of the vascular wall and thereby to support the functioning of
      mechanisms supporting physical thermoregulation. The results of the study give
      evidence of the stimulatory influence of the described method on the adaptive and
      protective potential of the organism. It is concluded that the proposed scheme of
      physiotherapeutic treatment may be used for prophylactic purposes.

PMID- 24437202
TI  - [Rehabilitation of the patients presenting with combined pathology:
      dyscirculatory encephalopathy and climacteric syndrome].
AB  - The present paper reports the data on rehabilitation of women presenting with
      combined pathology: dyscirculatory encephalopathy and climacteric syndrome. It is
      shown that the introduction of ozonotherapy and klimadynon, a herbal medicine
      possessed of the estrogen-like action, into combined rehabilitative treatment
      ensures the significant improvement of the parameters of interest, such as
      climacteric symptoms, short-term memory, lipid profile, endothelial function,
      cerebral circulation, and quality of life.

PMID- 24437203
TI  - [Optimization of the treatment of the patients presenting with chronic venous
      insufficiency in the lower extremities with the use of the modern methods of
      thalassotherapy].
AB  - The introduction of thalassotherapy (seaweed wraps cold) into the standard drug
      therapy and elastic compression techniques increases the effectiveness of
      conservative treatment of the patients presenting with chronic venous
      insufficiency due to the influence of biologically active components of brown
      algae that help to improve microcirculation, lymphatic drainage function, and
      peripheral hemodynamics. These effects lead to a decrease in the severity of
      hypoxia, enhancement of tissue trophism, promotion of inflammatory processes,
      reduction of the clinical manifestations of the disease, and improvement of the
      patients' quality of life.

PMID- 24437204
TI  - [A new approach to the treatment of patients presenting with bronchial asthma and
      concomitant allergic rhinitis].
AB  - The present study included 73 patients presenting with bronchial asthma (BA) and
      concomitant allergic rhinitis (AR). Based on the results of their examination, a
      program of their two-step treatment was proposed including elimination therapy
      during 5-7 days followed by the combined treatment with the use of physical
      factors, such as peloid therapy, supratonal frequency currents, inhalations,
      massage, and remedial gymnastics. This approach allows to significantly reduce
      the frequency of clinical manifestations of the primary and concomitant diseases.
      Specifically, the incidence of daytime choking fits decreased by 66.7%, coughing
      by 76.7%, nasal stiffness by 60%, and rhinorrhea by 62,6 with the simultaneous
      acceleration of the overall clinical effect by 3-4 days. The requirement for
      short-acting broncholytic agents decreased after the treatment by 56.7%. Its anti
      inflammatory effect in the upper and lower respiratory tract was confirmed by the
      results of endoscopic examination of the nasal cavity (the occurrence of mucosal
      hyperemia and mucosal oedema decreased by 70% and 60% respectively whereas the
      presence of secretion in the nasal passages was recorded 76.7% less frequently
      than prior to the treatment). Cytological studies of surface epithelium revealed
      reduced neutrophilia and eosinophilia, decreased number of goblet cells in nasal
      mucosa, and lowered content of sialic acids, IL-1, and IL-6 in nasal lavage.
      Combined therapy improved the patency of both upper and lower respiratory tract.
      Moreover, the number of patients with the totally controlled clinical course of
      BA increased by 66.6%. It was shown that remission of BA and AR persisted within
      10 and 8.2 months after the treatment respectively.

PMID- 24437205
TI  - [The results of the application of the pre-formed physical factors and
      neuroprotective therapy for the rehabilitative treatment of the patients with
      diabetic retinopathy].
AB  - To evaluate the effectiveness of the neuroprotective agent used to treat the
      patients presenting with non-proliferative diabetic retinopathy. The study
      included 114 patients (228 eyes) at the age varying from 42 to 70 who presented
      with diabetes mellitus and non-proliferative diabetic retinopathy. Three groups
      were formed depending on the mode of treatment. The patients in main group
      underwent endonasal electrophoresis of 0.1% semax preparation. Patients of the
      comparison group were treated with intranasal instillations of semax and those of
      the control group received only standard hypoglycemic therapy and treatment with
      Doxy-Hem. The patients of the first two groups showed positive dynamics of the
      studied functional characteristics (visual, perimetric, and electrophysiological
      ones). The most pronounced and long-standing (up to 12 months) positive effect on
      the visual function was documented in the main group. The results of the present
      study give reason to recommend the inclusion of endonasal electrophoresis in the
      combined rehabilitation treatment of the patients presenting with diabetes
      mellitus and non-proliferative diabetic retinopathy.

PMID- 24437206
TI  - [The influence of low-intensity intravenous laser irradiation of the blood on the
      endothelial function in the patients presenting with gastroesophageal reflux
      disease].
AB  - The present study included 100 patients presenting with gastroesophageal reflux
      disease (GERD) including 68 (68%) women and 32 (32%) men. They were divided into
      2 groups, with the study group comprised of 70 patients and the control one
      containing 30 patients. The objective of the study was to estimate the influence
      of low-intensity intravenous laser irradiation of the blood on the NO-producing
      function of vascular endothelium in the patients suffering GERD. The results of
      the study indicate that traditional medicamental therapy of the patients with
      GERD does not produce a significant improvement of plasma levels of stable nitric
      oxide metabolites whereas low-intensity intravenous laser irradiation of the
      blood results in well apparent normalization of this parameter regardless of its
      initial value, either high or low.

PMID- 24437207
TI  - [The effectiveness of the spa and health resort treatment for the pre-gravid
      preparation of the women at high risk of obstetric and perinatal pathology].
AB  - Chronic recurrent inflammatory diseases of the small pelvis are known to be
      responsible for the development of the adhesive process and infertility.
      Therefore, they require surgical treatment and increase the risk of obstetric and
      perinatal pathology. The present study was focused on the assessment of
      therapeutic and prophylactic effectiveness of the application of natural and
      preformed physical factors for the pre-gravid preparation of the patients
      presenting with gynecological problems and pregnant women at high risk of
      obstetric and perinatal pathology based at the spa and health resort facilities
      of the Krasnodar Krai (region). The treatment included aero-, helio-, and
      thalassotherapy, transcranial electroneural stimulation, UHF therapy, hydrogen
      sulfide or iodine-bromine therapy. A total of 267 women were included in the
      study. Pregnancy was documented in 52% of the 144 patients who comprised the main
      group and underwent a course of rehabilitative treatment; it developed within 3-5
      months after therapeutic and prophylactic laparoscopic procedures. The frequency
      of obstetric and perinatal pathology in this group significantly decreased in
      comparison with that among the control patients which allowed to greatly reduce
      material and financial expenditures.

PMID- 24437208
TI  - [The problems of antihypertensive balneotherapy].
AB  - This review is devoted to the challenging problems of balneotherapeutics, such as
      the mechanisms of antihypertensive balneotherapy and its optimization. The
      experience of the authors with the practical application of chloride - sodium,
      iodine - bromide, and hydrogen sulfide mineral baths is analysed in comparison
      with the literature data. The role, dosage regimen, and duration of
      balneotherapeutic treatment as well as the effectiveness of its combination with
      medicamental therapy are considered. The authors hope that the discussion of
      these issues will be conducive to the solution of problems currently facing
      modern antihypertensive balneotherapy.

PMID- 24437209
TI  - [On the mechanism of action of cryomassage of the abdominal wall in the patients
      presenting with gastroduodenal pathology].
AB  - The mechanism of action of cryomassage of the abdominal wall in the patients
      presenting with gastroduodenal pathology is considered. The authors suppose that
      the positive effect of cryotherapy is underlain by normalization of
      microcirculation in the digestive organs and the resulting improvement of energy
      and plastic support of intracellular processes, e.g. phosphorylation.

PMID- 24437210
TI  - [Peat peloids from the Bichevskoye deposits of the Khabarovsk region and their
      physicochemical characteristics].
AB  - The authors present information about the resources of sulfide silt peloids at
      the Bichevskoye peat field of the Khabarovsk region. Their physicochemical
      properties, the fragmentary carbon composition of the liquid and concentrated
      peat phases, as well as the elemental composition of the organic compounds
      present in peat hydrolysates are described. The results of high-tech
      investigations confirm the presence of biologically active humic substances in
      the peat.

PMID- 24437211
TI  - [Doctor M.P. Ogranovich (1848-1904). On the history of development of health
      resort and spa business in Russia].

PMID- 24437212
TI  - [Component-resolved diagnosis is a new era in clinical allergology].
AB  - The paper describes the fundamentals and benefits of a new allergy diagnostic
      technique based on recent advances in molecular biology and biotechnology.
      Component-resolved diagnosis allows IgE antibodies against purified molecules
      (individual allergen components) to be revealed. Microanalysis is made using
      microarrays with applied molecules (allergen components) obtained in a
      recombinant fashion or extracted from natural raw materials. The authors present
      a current classification of animal and plant allergens and show the value of
      component-resolved diagnosis in clinical practice, by using specific clinical
      examples.

PMID- 24437213
TI  - [Possibilities of rational combination antihypertensive therapy: results of
      HEMERA international clinical trial].
AB  - AIM: To evaluate the efficiency and safety of two treatment regimens using
      ramipril or losartan in combination with hydrochlorothiazide (HCT) and amlodipine
      in grade 1-2 arterial hypertension (AH). SUBJECTS AND METHODS: The prospective,
      international, multicenter, randomized, open-label, controlled trial with
      parallel groups included 347 AH patients in Russia (n = 166), Croatia, and
      Ukraine. The follow-up was 12 weeks in patients not receiving antihypertensive
      therapy (AHT) and 13 weeks in those who had previously received AHT with regard
      to a washout period. The basis for two treatment regimens was ramipril or
      losartan. If no target blood pressure (BP) was achieved, amlodipine or HCT was
      added at week 4 and a third antihypertensive drug (AHD) was used 8 weeks later.
      RESULTS: At the inclusion, clinical BP was 157.64/95.5 mm Hg in 332 (61%) AH
      patients aged 55.9 +/- 11 years. At week 4 of monotherapy with ramipil 5 mg or
      losartan 50 mg, BP was reduced to 141.9/87.4 mm Hg. Addition of a second AHD
      further lowered BP to 131.8/81.9 mm Hg (to 127.6/79.7 at 12 weeks of treatment; p
      < 0.001). After 4 weeks of treatment with ramipril 5 mg or losartan 50 mg, 35% of
      the patients achieved target BP. At weeks 8 and 12, double or triple AHT
      increased the number of patients achieving the target level up to 75 and 94%,
      respectively. When losartan was used as monotherapy, about one third of the
      patients achieved target BP; 20 and 22% of the patients required the addition of
      a second AHD (HCT and amlodipine, respectively). Only 10% of the patients needed
      to take a combination of three AHDs. Nearly one third of the patients achieved
      target BP during monotherapy with losartan or ramipril. Double AHT involving
      ramipril or losartan in combination with the diuretic or amlodipine was used in
      18 and 20% and in 22 and 24% of the patients, respectively. 28 and 19% of the
      patients received triple therapy including ramipril or losartan, amlodipine, and
      HCT. The most common adverse reactions were dizziness (2.4%), fatigue (1.8%), and
      coughing (1.2%). CONCLUSION: In the patients with grades 1-2 AH, the treatment
      regimens using basic therapy with ramipril or losartan proved to be highly
      effective and allowed target BP to be achieved in 94% of cases. Both treatment
      regimens were comparable in view of safety; slight side effects occurred rarely
      (in less than 2.5% of the patients) and required that the treatment should not be
      discontinued.

PMID- 24437214
TI  - [Impaired cardiac structural and functional parameters in patients with chronic
      heart failure and diabetic cardiac autonomic neuropathy].
AB  - AIM: To reveal the specific cardiac structural and functional features in
      patients with chronic heart failure (CHF) and diabetic cardiac autonomic
      neuropathy (CAN). SUBJECTS AND METHODS: Ninety patients aged 45-70 years with
      Functional Class I-III CHF in the early post-myocardial infarction period and
      with type 2 diabetes mellitus (DM2) were examined. A study group of 60 patients
      had signs of CAN (Group 1); a control group of 60 patients presented with CHF and
      DM2 without signs of CAN (Group 2). RESULTS: The patients with CHF and DM2 with
      the manifestations of CAN were found to have higher left ventricular mass indices
      and greater QT dispersion than those with CHF and DM2 without CAN; there was a
      significant decrease in heart rate variability and a statistically significant
      preponderance of hypersympathicotonia. CONCLUSION: A clinically important
      relationship was found between cardiac autonomic dysregulation, CAN severity in
      patients with CHD and DM2 and cardiac structural and functional parameters.

PMID- 24437215
TI  - [Prothrombotic state in patients with metabolic syndrome: an association with
      inflammation].
AB  - AIM: To comprehensively study hemostasis pathology and its association with the
      laboratory markers and mediators of inflammation in patients with metabolic
      syndrome (MS). SUBJECTS AND METHODS: One hundred and eleven patients with type 2
      diabetes mellitus, who were diagnosed as having MS, were examined. Vascular
      platelet and secondary hemostases and anticoagulant and fibrinolytic systems were
      evaluated, by performing the complete clinical, laboratory, and instrumental
      study accepted in a specialized endocrinology clinic. The blood concentrations of
      high-sensitivity C-reactive protein and proinflammatory cytokines were determined
      in all the patients with MS and control persons (n = 50). RESULTS: It was found
      that in patients with MS, hemostasis pathology that might be classified as the
      combined form of a prethrombotic state, which was caused by different types of a
      constellation of vascular-platelet and plasma hemostases, as well as
      physiological anticoagulant deficiency, was linked to the laboratory markers and
      mediators of subclinical inflammation. CONCLUSION: In the patients with MS,
      subclinical systemic inflammation is of substantial importance for the mechanisms
      of a prethrombotic state.

PMID- 24437216
TI  - [Cerebrovascular diseases and metabolic syndrome].
AB  - AIM: To study various aspects of cerebrovascular diseases (CVD) in the presence
      of metabolic syndrome (MS). SUBJECTS AND METHODS: A comprehensive clinical,
      laboratory, ultrasound, and neuroimaging study was conducted in 514 patients with
      symptomatic and asymptomatic atherosclerotic lesion of the internal carotid
      artery and MS. RESULTS: MS was found and proven to affect the following factors:
      a) the course and progression of carotid artery (CA) atherosclerotic lesion with
      transformation of its asymptomatic to symptomatic state; b) the structure and
      instability of an atherosclerotic plaque; c) the magnitude of blood theological
      changes; d) endothelial dysfunction; e) white matter changes; f) the clinical
      features of both acute and chronic CVD and the development of cognitive
      impairments. CONCLUSION: The association of the atherogenic activity of major
      components of MS, such as hyperinsulinemia, hypertension, dyslipidemia, and
      obesity, in the presence of dysregulated hemostasis and blood rheology
      substantially increases the risk of a progressive CA atherosclerotic process even
      in its asymptomatic course and accordingly favors the development and progression
      of different manifestations of CVD.

PMID- 24437217
TI  - [Dilated cardiomyopathy in patients with schizophrenia].
AB  - AIM: To study the frequency of pathoanatomic and some clinical signs of dilated
      cardiomyopathy (DCM) in schizophrenic patients (SPs). SUBJECTS AND METHODS:
      Autopsy records were studied in 838 SPs treated at a psychiatric hospital in 1952
      to 2007. The records were used to select DCM cases (n = 74) and sudden deaths (n
      = 101) and to examine 339 electrocardiograms (ECG). The 2006-2007 information
      obtained in the dissecting rooms of three Tver hospitals (1413 sections) was
      analyzed. RESULTS: DCM was absent (neuroleptics were not used) before 1956. With
      the application of neuroleptics, the diagnosis of DCM cases significantly
      increased and its rate was 14.2% among the dead SPs. DCM might be a cause of
      sudden death in 21.8% of SPs. The rate of pathological ECG signs noticeably
      increased with the longer use of neuroleptics. In the hospital-wide network, the
      detection rate for DCM was 0.5% of the autopsies. CONCLUSION: The use of
      neuroleptics, in SPs in particular, may lead to the development of DCM.

PMID- 24437218
TI  - [Pregnancy and labor problems in patients with acute porphyria].
AB  - AIM: To evaluate the impact of developing pregnancy on porphyrin metabolism in
      reproductive-aged women with acute porphyria (AP). SUBJECTS AND METHODS: The
      prospective clinical data of 33 pregnancies were analyzed in 28 patients with the
      established diagnosis of AP. The latter was verified by the quantitative analysis
      of 24-hour urinary porphyrin excretion and the diminished activity of the
      pathognomonic enzyme. RESULTS: Each case was analyzed in detail according to
      different criteria. Poor prognostic factors for pregnancy are identified in AP.
      The used curation policy for pregnant patients is described. The pregnant women
      with occurring AP episodes are subdivided into clinical groups requiring
      different curation approaches. The scheme for the used working protocol is given.
      CONCLUSION: The accumulated experience with curating the patients with AP will be
      able to avoid the existing prohibitory practice, providing a way to develop a new
      quality of life in the patients' families.

PMID- 24437219
TI  - [Treatment for acute promyelocytic leukemia during pregnancy].
AB  - AIM: To study the experience in managing patients with acute promyelocytic
      leukemia (APL) diagnosed in different periods of pregnancy. SUBJECTS AND METHODS:
      Nine women with APL were treated in 1998-2013. When APL was diagnosed in the
      first trimester of pregnancy, the latter was terminated (n = 1); when its
      diagnosis was made in the second trimester, chemotherapy (CT) followed by
      delivery (D) was performed (n = 3); when it was done in the third trimester, D
      followed by CT was done in relation to gestational age (n = 2) or these were
      performed at a later gestational age (n = 1). APL was treated in 5 and 1 patients
      according to the AIDA protocol and the 7+3 plus ATRA one, respectively. RESULTS:
      All the patients with APL achieved remission after the first cycle of induction
      CT; 5 of the 6 patients did at the moment of delivery; one patient underwent
      emergency delivery during cytopenia after the cycle. The gestational age at
      delivery after CT was 34 (34-40) weeks. Spontaneous term labor occurred in 2
      patients at an obstetric hospital. Cesarean section was made in 4 of the 6
      patients. All babies were born alive, healthy, and without developmental
      abnormalities. Their age at the time of analyzing the results was 2.5 months to
      15 years. Four of the 9 patients are presently alive. Late recurrences occurred
      in 3 (33%) patients. The median overall survival is 26 (0.25-128) months; the
      median relapse-free survival is 17.5 (0-127) months. CONCLUSION: APL treatment in
      pregnant women, which is aimed at saving two lives, is effective and reasonable.

PMID- 24437220
TI  - [The vascular wall in postmenopausal women with hypothyroidism and hypertension].
AB  - AIM: To study a relationship between thyroid function and the stiffness of great
      arteries in postmenopausal women with arterial hypertension (AH). SUBJECTS AND
      METHODS: The trial enrolled 76 postmenopausal patients with clinical
      hypothyroidism (CHT) (n = 24) or subclinical hypothyroidism (SCHT) (n = 52) and
      AH; a control group consisted of 40 postmenopausal women with euthyroidism. Body
      mass index (BMI), waist and hip circumferences, blood pressure (BP), thyroid
      stimulating hormone (TSH), free thyroxine, free triiodothyronine, total
      cholesterol, triglycerides were determines; volumetric sphygmography was
      performed. Brachial-ankle pulse wave velocity (baPWV) was measured; cardio-ankle
      vascular index (CAVI) and ankle-brachial index (ABI) were determined. RESULTS:
      The patients with CHT or SCHT and the controls were matched for age, BMI, BP, and
      heart rate. TSH levels in patients with SCHT (6.23 (5.27; 8.22) microU/ml) and in
      those with CHT (11.8 (9.09; 22.7) microU/ml) were statistically significantly
      higher than in the control group (2.25 (1.5; 2.72) microU/ml) (p < 0.05). BaPWV
      in the patients with SCHT (14.35 (12.5; 15.5) m/sec) and in those with CHT (13.75
      (13.05; 15.25) m/sec) was also statistically significantly higher than in the
      control group (12.85 (12; 13.9) m/sec) (p < 0.05). Comparison of ABI and CAVI
      revealed no significant differences between the groups. Univariate analysis of
      the findings showed a significant impact on higher arterial stiffness in the SCHT
      and the CHT groups. Total cholesterol levels were significantly higher in the
      SCHT group than in the control one. CONCLUSION: The patients with AH and
      hypothyroidism versus their peers with AH and without thyroid function had
      significant rises in blood cholesterol levels and arterial stiffness. The rise in
      lipid levels was significantly marked only in the patients with SCHT; and baPWV
      equally increased in both the SCHT and the CHT groups.

PMID- 24437221
TI  - [Optimization of an approach to solving the problem of a barren marriage in
      secretory azoospermic men].
AB  - AIM: To compare the efficiency of using different interventional procedures for a
      barren marriage in case of secretory azoospermia (SAS). SUBJECTS AND METHODS: The
      trial enrolled 110 patients aged 25 to 54 years with SAS. The levels of sexual
      hormones were determined; ovarian punch biopsy was performed. RESULTS: Decreased
      volume of the ovaries was noted in 85.3% of the patients; diffuse or focal
      changes in their parenchyma were seen in 65.7%. There was an increase of follicle
      stimulating hormone levels and a reduction in testosterone ones.
      Hyperestrogenemia was identified in 26.5% of the patients. The level of inhibin B
      was lower in all the patients. The efficiency of standard testicular sperm
      extraction for cryopreservation was achieved in 28.7% of the patients and that of
      a microsurgical technique was in 56.7%. The wives of 37 out of the 57 patients
      included in an assisted reproductive technology program were more than 12 weeks
      pregnant after 95 intracytoplasmic sperm injection cycles. CONCLUSION: The
      microsurgical technique is most effective in achieving the successful treatment
      of patients with azoospermia in order to prevent male infertility.

PMID- 24437223
TI  - [Circadian rhythm sleep disorders in megalopolis dwellers].

PMID- 24437222
TI  - [Experience with selenium used to recover adrenocortical function in patients
      taking glucocorticosteroids long].
AB  - AIM: To study the effect of selenium on adrenocortical function in patients
      taking glucocorticosteroids (GCS) long. SUBJECTS AND METHODS: The study included
      56 patients who had been long taking oral GCS for the underlying disease.
      Adrenocortical function was evaluated by a short synacthen test; adrenal
      insufficiency (mean cortisol level 8.2 microg/dl) was identified in 52 patients.
      A study group of patients (n = 35) was given selenium 200 microg/day. A control
      group (n = 17) with the detected adrenal insufficiency did not take it. All the
      patients (n = 52) continued to receive standard therapy for the underlying
      disease, including oral GCS. RESULTS: Adrenal function was reexamined 6 months
      later; the two paired-samples t-test indicated a statistically significant
      increase in cortisol levels up to 23.20 +/- 4.2 microg/dl (p < or = 0.05) in the
      patient group receiving selenium in addition to the basic therapy. In the control
      group, the function did not recover (cortisol levels were 8.6 and 9.8 microg/dl
      at baseline and at 6 months, respectively; p < or = 0.05). CONCLUSION: The
      experience with selenium 200 microg/day given long to patients with adrenal
      insufficiency caused by the long-term use of GCS shows that the agent is
      effective in recovering adrenocortical function.

PMID- 24437224
TI  - [Chronic obstructive pulmonary disease exacerbation. Do we use all possibilities
      of outpatient therapy?].
AB  - Chronic obstructive pulmonary disease (COPD) exacerbations are evaluated from a
      history of the disease, its clinical symptoms, and laboratory tests. The most
      common causes of a COPD exacerbation are upper respiratory tract and
      tracheobronchial infections. The exacerbation severity usually corresponds to the
      magnitude of clinical manifestations of COPD during its stable course. Successful
      treatment in patients with a COPD exacerbation is determined by its timely
      diagnosis. When treating patients with a mild or moderate exacerbation of Stages
      I-II COPD in an outpatient setting, it is advisable to use ascoril having
      broncholytic, mucolytic, and mucokinetic properties along with antibiotics and
      glucocorticosteroids, if clinically indicated.

PMID- 24437225
TI  - [Erectile dysfunction and obesity].
AB  - The review considers the relationship between obesity and erectile dysfunction
      (ED). Obesity is associated with the high prevalence of ED; however, the
      pathophysiological link between these conditions has yet to be adequately
      investigated. Visceral obesity leads to the enhanced activity of inflammatory
      responses and, thus, endothelial dysfunction and decreased plasma testosterone
      levels, which favors the development of hypogonadism and increases the risk of
      vascular diseases. Endothelial dysfunction and androgen deficiency in turn give
      rise to ED.

PMID- 24437226
TI  - [Antiviral therapy and risk for hepatocellular carcinoma in chronic viral
      hepatitis].
AB  - Hepatocellular carcinoma (HCC) is one of the most common human malignancies in
      incidence and mortality, which develops in the majority of patients in the stage
      of cirrhosis. Because of the major etiological role of hepatitis viruses, the
      prevention of HCC is vaccination against hepatitis B virus and successful
      antiviral therapy for chronic hepatitis B and C.

PMID- 24437227
TI  - [Impact of bariatric surgery on the absorption of nutrients in patients with
      obesity].
AB  - The review considers disturbed metabolism of vitamins, minerals, and protein in
      patients following bariatric surgery. The positive effect of the surgery is
      proven; however, postresection syndromes that may further occur determine not
      only a patient follow-up, but also timely therapeutic interventions to prevent
      hypovitaminoses, anemia, and mineral metabolic disturbances. There are
      conflicting data on the incidence of these abnormalities. No guidelines for their
      treatment and prevention have been elaborated.

PMID- 24437228
TI  - [Medical and psychological rehabilitation of patients and disabled persons].
AB  - The paper unveils the concept of medical rehabilitation and defines its place in
      clinical medicine. It underlines the inextricable link and interaction of
      different components of a rehabilitation system. The value of the psychological
      aspect of rehabilitation is considered. Categories of patients and disabled
      persons who need psychological rehabilitation are identified; a classification of
      personal reactions to disease and the changes in the psychological state of
      patients in different periods after disease onset are given. The factors
      influencing the process of psychological readjustment in patients and the
      disabled are analyzed. The psychological rehabilitation system for patients and
      disabled persons is considered in detail. Data on its medical and socioeconomic
      efficiency are presented.

PMID- 24437229
TI  - [Headache associated with sexual activity: diagnostic difficulties and management
      tactics].
AB  - Headache associated with sexual activity (HASA) is a common and benign form of
      primary headache in most cases and has a favorable prognosis. However, even a
      single episode of primary headache is a cause for an immediate and thorough
      examination to rule out the secondary nature of cephalgia. The paper considers
      the pathogenesis, differential diagnosis, and principles in the treatment of
      patients with this disease.

PMID- 24437230
TI  - [Relationship between visceral diseases and oral health].
AB  - The paper analyzes the literature showing that there is not only a phylogenetic
      relationship, but also a functional one between visceral diseases and oral
      health. It gives data on the unity of the occurrence of somatic and dental
      diseases. There is evidence for cause-and-effect relationships between them,
      which arise from immune imbalance, interleukin dysregulation, and nonspecific
      inresistance. There was a negative comorbidity of visceral diseases and oral
      health, namely, a relationship of dental diseases to the patients' general
      condition, as well as the impact of the foci of chronic oral infection on the
      development of systemic diseases. Mechanisms of a relationship between oral
      infection and secondary systemic manifestations are also described. It has been
      established that transient bacteremia odontogenic is detected at a dental visit
      and conditions for its transformation to any infectious diseases are also
      outlined. Unified systems approaches to treating polymorbidity are found to be
      needed.

PMID- 24437231
TI  - [Tracheal diverticula].
AB  - Tracheal diverticula (TD) are a rare congenital or acquired condition. The
      diagnosis of TD is based on the data of multislice spiral computed tomography and
      fibrotracheal bronchoscopy. DTs are most frequently located in the right, may be
      solitary or multiple, uni- or multilocular. Uncomplicated DTs generally have no
      characteristic clinical features. Their symptoms can arise from the compression
      of adjacent organs or the addition of secondary bacterial infection and most
      commonly appear as cough. Differential diagnosis is mainly made with pharyngeal
      and laryngeal cysts and pharyngoesophageal diverticula. Asymptomatic TDs usually
      require no treatment. Surgical TD excision is possible in case of compression of
      adjacent organs and infection.

PMID- 24437232
TI  - [Comparative clinical and morphological characteristics of incidental and
      symptomatic renal cell carcinoma].
AB  - Over the last two decades, marked increase in detection of incidental or
      asymptomatic renal cell carcinoma (RCC) in developed countries was observed. The
      study included 268 patients aged from 25 to 92 years with RCC, which underwent
      evaluation and treatment in urology clinic MRSRCI for the past 5 years. There
      were no significant differences in the frequency of histological types of RCC
      between incidental and symptomatic tumors. Among incidental neoplasms with clear-
      cell structure, tumor with small size--up to 4 cm (T1a stage) and moderate to
      high degree of differentiation (G 1-2 according Fuhrman) were predominant.
      Papillary variant of RCC was detected at a higher stage of the disease and
      characterized by a high degree of nuclear atypia, which indicates its high
      malignant potential. Chromophobe RCC was usually diagnosed at T3 stage. The
      average age of men and women with chromophobe RCC was 46.5 +/- 6.8 years; there
      were no age difference in patients with symptomatic and incidental RCC. Among the
      benign tumors of the kidneys, angiomyolipoma was most commonly diagnosed--in 13
      (53.8%) cases. Thus, incidental tumors have a better prognosis than symptomatic
      tumors.

PMID- 24437233
TI  - [Extravaginal transposition of the urethra in the treatment of post-coital
      cystitis].
AB  - From 2005 to 2013, 106 patients with post-coital cystitis underwent surgery. Of
      these, vaginal ectopia of urethral meatus was diagnosed in 19 (17.9%), and
      hypermobility of the distal urethra in 87 (82.1%). 28 (26.4%) women underwent the
      traditional plasty of distal urethra by O'Donnell method (group 1) and 78 (73.6%)
      patients underwent surgery using new method of extravaginal transposition of the
      urethra developed in our clinic (group 2). In group 1, satisfactory results were
      obtained in 23 (82.1%) patients, poor results--in 5 (17.9%) patients; in group 2,
      in 77 (98.7%) and 1 (1.3%) patients, respectively (p < 0.05). The disappointing
      results were attributable to the divergence of seams, reverse bias of urethra and
      recurrence of the disease. The use of method of extravaginal transposition of the
      urethra compared with a standard method allows to reduce the trauma of surgery,
      improve reliability of fixing the urethra, reducing the risk of its restriction
      and disease recurrence.

PMID- 24437234
TI  - [Automated decision making support system for urologists on the prediction and
      the prevention of stone formation in urolithiasis].
AB  - This article describes a decision making support system for urologists on the
      prediction and management of preventive interventions for urolithiasis using
      fuzzy logic decision-making device. Dictionary of informative signs and alphabet
      of classes are formed. The formulas for calculating the membership functions
      according to the known features are developed; these formulas allow to calculate
      the certainty factors for pertaining of inspected object to the desired class by
      means of iterative rules of rule of logical inference. Based on comparison of the
      values obtained with the threshold certainty factors, dephasification of
      conclusion is produced. In accordance with the obtained decision rules, control
      algorithm for the prevention measures in urolithiasis is developed. To test the
      effectiveness of "operation" of the synthesized decision rules, the certainty
      factors were calculated or 200 patients with urolithiasis, which were divided
      into two groups according to the results of observation during the year depending
      on the presence of recurrence. The analysis of the intersection of histograms of
      distribution of coefficient values showed high diagnostic efficiency (0.94) of
      synthesized decision rules.

PMID- 24437235
TI  - [Laboratory diagnosis of urinary tract injuries].
AB  - In 238 patients with various surgical diseases of the abdominal cavity,
      concentration of creatinine in serum and peritoneal cavity exudate was evaluated.
      In the most cases, no significant differences in creatinine levels were found in
      these biological fluids, that allowed to recommend to use creatinine level in the
      exudate, flowing along drainages, as a parameter for dynamic control of nitrogen
      excretion renal function. Significant difference in the serum creatinine level
      and exudate creatinine level was found in cases of injury of organs of urinary
      system and the penetration of urine into the peritoneal cavity. In these cases (n
      = 16), creatinine level in the abdominal exudates exceeded the serum level (p <
      0.01), that allowed to provide a new method for diagnosis of lesions of the
      urinary tract.

PMID- 24437236
TI  - [The efficacy and safety of cefixime and amoxicillin/clavulanate in the treatment
      of asymptomatic bacteriuria in pregnant women: a randomized, prospective,
      multicenter study].
AB  - The study was aimed to the evaluation of efficacy and safety of cefixime and
      amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant
      women. A prospective, multicenter, randomized study that included 112 pregnant
      women with asymptomatic bacteriuria was performed. 58 women were randomized in
      group 1 (cefixime [suprax solutab] 400 mg 1 time a day, 7 days), 54 women were
      included in group 2 (amoxicillin/clavulanate [amoksiklav] 625 mg 3 times a day, 7
      days). The average age of the patients in group 1 was 25.2 +/- 6.6; in group 2-
      26.6 +/- 5.8 years. Physical examination, evaluation of complaints, collection of
      data on adverse reactions, and bacteriological analysis of urine were performed
      after enrollment in the study at visit 2 (day 10 +/- 1) and 3 (day 35 +/- 2).
      Comparable effectiveness of cefixime and amoxicillin/clavulanate in the treatment
      of asymptomatic bacteriuria in pregnant women was found. Eradication of the
      pathogen and sustained bacteriological response were observed in 94.8 and 92.7%
      of women treated with cefixime, and in 98.2 and 92.5% of women treated with
      amoxicillin/clavulanate, respectively (P > 0.05). At the same time, the use of
      amoxicillin/clavulanate compared with cefixime significantly higher was followed
      by the development of adverse reactions (13% and 1.7; respectively; P = 0.02).
      Seven-day courses of cefixime at a dose 400 mg 1 time a day and
      amoxicillin/clavulanate at a dose of 625 mg 3 times a day are high-effective
      treatment regimens for asymptomatic bacteriuria in pregnant women in Russia. The
      use of amoxicillin/clavulanate is significantly more often accompanied by the
      development of adverse reactions compared with cefixime.

PMID- 24437237
TI  - [Assessment of equivalence of the original tamsulosin and its generics].
AB  - Generics constitute a significant part of the modern pharmaceutical market. The
      use of generics in the case of their equivalence to the original drug allows to
      reduce the burden of health care costs. Often, however, the quality of generics
      does not match that of the original drug. The results of study suggest that the
      investigated generics of tamsulosin may not be fully recognized as
      pharmaceutically equivalent to the original drug.

PMID- 24437238
TI  - [The effectiveness of use of prolit in patients with ureteral stone].
AB  - The study was aimed to the evaluation of the efficacy of prolit in patients with
      urolithiasis and localization of stone in the ureter. 225 patients with various
      localization of solitary ureteral calculi ranged from 0.4 to 0.7 cm were under
      observation. Depending on the treatment, the patients were divided into two
      groups. The study group (n = 175) has received prolit for 30-40 days, control
      group (n = 50) has received standard therapy. As a result of treatment,
      spontaneous discharge of ureteral stone was registered in 158 (90.3%) patients of
      study group and only in 21 (42%) patients of control group. Renal colics during
      treatment were recorded four times more often among patients of control group.
      The intensity of pain in patients receiving prolit was less pronounced.

PMID- 24437239
TI  - [Therapy of rapid ejaculation using dietary supplement "NeyroDoz": results of a
      multicenter non-randomized clinical study].
AB  - The main aim of the study was to determine the effectiveness of a multicomponent
      dietary supplement NeyroDoz in patients with rapid ejaculation. We examined 50
      patients with rapid ejaculation (premature ejaculation), who were recruited in 9
      clinical centers in different regions of Russia. These patients received
      NeyroDoz, 2 capsules twice a day for one month, followed by a control observation
      for 1 month. In study group of patients, symptomatic improvement was achieved in
      45 (90%) of 50 patients at 4-week observation target date. In assessing the
      impact of NeyroDoz on different groups of symptoms, it was found that it
      significantly increases the average time of sexual intercourse by 2 times,
      increases the orgasm brightness, reduces the severity of psychosomatic component
      and has a positive effect on all components of the copulative cycle. In assessing
      the afterimpression, this effect was maintained throughout the period of follow
      up.

PMID- 24437240
TI  - [Potentials for the correction of endothelial and erectile dysfunction in
      patients after coronary artery bypass grafting].
AB  - The study was aimed to the evaluation the effect of NO- synthase inducer impaza
      on endothelial function and erectile function in patients undergoing coronary
      artery bypass grafting (CABG). The study involved 127 men with stable coronary
      artery disease (CAD), aged 55.8 +/- 5.3 years, which were planned on CABG. The
      survey included assessment of IIEF score and blood lipid levels, registration of
      nocturnal penile tumescences, postcompression tests on the shoulder and cavernous
      arteries. Endothelial function was assessed as the plasma levels of nitric oxide
      (NO) and endothelin-1 (ET-1). The comparison group of patients (n = 67) were
      treated with standard rehabilitation program, and the study group (n = 67)
      additionally has received impaza 1 tablet a day for 24 weeks. It is shown that in
      patients with erectile dysfunction (ED) undergoing CABG, the use of impaza for 24
      weeks facilitates optimal dynamic expression of the ED. But a year after the
      operation, there were marked deterioration in erectile function, indicating a
      short-term effect of action of impaza that may require its longer use. In
      addition, 6 months after CABG, patients receiving impaza had better indicators of
      functional activity of the endothelium in shoulder and cavernous arteries
      compared with patients who received conventional rehabilitation; one year after
      surgery, however, there were no significant differences in these parameters.
      Restorative treatment using impaza in CAD patients after myocardial
      revascularization operations has positive influence on the NO, ET-1 levels, which
      is reflected in the functional state of the endothelium and characterized by an
      increase in vasodilator properties and decrease in vasoconstrictor properties.

PMID- 24437241
TI  - [Correction of erectile dysfunction in patients with benign prostate hyperplasia
      using daily administration of tadalafil 5 mg against the background of combined
      drug therapy].
AB  - The study included 59 patients with benign prostate hyperplasia (BPH) and
      erectile dysfunction (ED), inhibited inflammation in the prostate gland and with
      normal or medically normalized levels of total testosterone. All the patients
      underwent conservative therapy using dutasteride and tamsulosin, 21 of them
      (group 2) additionally received tadalafil 5 mg daily. Efficacy of treatment was
      assessed by self-assessment questionnaire of patients before treatment and 12
      weeks after therapy. In group 1 of patients, the dynamics of the erectile
      function, sexual satisfaction and quality of life for patients was not revealed.
      In the group 2, improvement in erectile function in an average of 19 points was
      shown (IIEF-5 questionnaire). According to the AMS questionnaire, improvement in
      sexual function was demonstrated; in patients with compensated androgen
      deficiency, however, response to the treatment with tadalafil was less
      pronounced. According to BSFI score after 3 months of therapy with tadalafil,
      indicator of overall satisfaction of sexual life improved to 2.4 points (p <
      0.002). According to the Hospital Anxiety and Depression Scale, anxiety in
      patients was reduced to the permissible values (p < 0.0002), the level of
      depression was decreased by almost 2-fold (p < 0.0002). The total IPSS score
      decreased from 13 to 9 points in average. The inclusion of tadalafil in complex
      of combined conservative therapy of patients with BPH not only improves sexual
      function but has a positive effect on symptoms of the disease and the
      psychological state of the patient.

PMID- 24437242
TI  - [Clinical and urodynamic evaluation of efficacy of conservative treatment of
      urination disorders in patients with benign prostate hyperplasia].
AB  - 17 patients (mean age, 61 +/- 1.7 years) with an benign prostate hyperplasia
      (BPH) and urination disorders were under observation. After examination by
      ultrasound, urodynamic and laboratory studies, patients received conservative
      combined therapy, including alpha1-adrenoblocker silodosin, L-carnitine, B
      vitamins and picamilon. As a result of the 4,5-month treatment, most of the
      symptoms were eliminated as evidenced by the decrease in IPSS score from 17 to 3;
      urodynamic parameters have improved that was recorded by the home uroflowmetry.
      It was concluded that the use of proposed combined therapy in patients with BPH
      as the first stage of treatment, followed by the administration of 5alpha
      reductase inhibitors or performing surgical correction in case of formation of
      bladder outlet obstruction is justified.

PMID- 24437243
TI  - [Clinical, laboratory and uretroscopic evaluation of the effectiveness of Safocid
      in the complex treatment of urethritis associated with sexually transmitted
      infections by using endoscopic techniques].
AB  - The study included 110 men suffering from sexually transmitted infections.
      Clinical diagnosis was made using modern hardware and instrumental methods of
      examination. It is shown that the combined preparation "Safocid" is a high
      effective drug for the etiotropic treatment of specific and non-specific
      urethritis, with elimination of causative microorganisms of sexually transmitted
      infections in 96.4% of cases.

PMID- 24437244
TI  - [Combined treatment of patients with lower urinary tract symptoms and erectile
      dysfunction].
AB  - In men of middle and older age group, urination disorders and erectile
      dysfunction are often combined. The role of phosphodiesterase type 5 inhibitors
      in the treatment of these patients remains uninvestigated. Prospective study
      included 38 patients with urination disorders and erectile dysfunction. The
      average age of the patients was 63.6 +/- 5.3 years. During first three months of
      observation, all patients have received alpha-adrenoblocker doxazosin at a dose
      of 4 mg once daily per os, the next three months--phosphodiesterase type 5
      inhibitor udenafil at a dose of 50 mg once daily per os was added to doxazosin. 3
      months after treatment, majority of patients reported improvement of urination.
      The statistically significant changes in BP and heart rate were not recorded,
      indicating a satisfactory tolerability and safety of doxazosin. Against the
      background of combined treatment during next 3 months, progressive improvement of
      erectile function (IIEF score 12.8 +/- 3.4 vs 18.4 +/- 3.7; p < 0.05), and
      regression of urination disorders, according to IPSS score (13.4 +/- 1.2 vs 11.2
      +/- 1.7; p < 0.05) were observed. Uroflowmetric indicators were not significantly
      changed. Based on experimental and clinical studies, it was suggested that the
      dysregulation of NO--cGMP system, pathological activation of Rho-kinase pathways,
      hyperactivity of autonomic innervation, atherosclerosis and impaired blood flow
      in the pelvic organs are the common pathophysiological mechanisms for LUTS and
      erectile dysfunction. The clinical efficacy of phosphodiesterase type 5
      inhibitors in the treatment of patients with these diseases is explained by its
      effects on these mechanisms.

PMID- 24437246
TI  - [Experimental validation of the use of ND:YAG-interstitial laser coagulation of
      the kidney].
AB  - Interstitial laser coagulation (ILC) is one of the effective methods of minimally
      invasive destruction of small renal tumors. For the safe use of ILC in clinical
      practice, it is necessary to select the optimal mode of action of laser radiation
      on the tissue of target organ and techniques for the procedure. The effects of
      ILC on kidney tissue in 6 rabbits weighing less than 3 kg and 5 mongrel dogs
      weighing up to 20 kg were investigated in vivo. The impact of ILC was made
      intraoperatively. Organ retrieval in experimental animals for the macro- and
      microscopic examination was performed immediately after the impact of ILC and at
      various times thereafter during the month in rabbits and 35 days in dogs.
      Morphological study in different periods after exposure allowed to establish
      phasing and volumes of changes in the tissues of the kidney, confirming the
      safety and efficacy of ND:YAG laser irradiation on kidney tissues. The results
      indicate the possibility of effective application of ILC of kidney tissues for
      destruction of small size tumors, without impairment of functions of the organ.

PMID- 24437245
TI  - [Modern tactics of management of patients with bilateral staghorn
      nephrolithiasis].
AB  - A comparative analysis of the effectiveness of open and percutaneous operations
      in the treatment of bilateral staghorn nephrolithiasis (SN) was performed. Of the
      38 patients with bilateral SN, stage operation (without discharge) was performed
      in 26 (68.5%) patients, and single-step operation--in 12 (31.5%) patients. For
      the 47 patients with bilateral SN, who underwent open surgery, the interventions
      were following: pelviolithotomy (64 operations), nephrolithotomy (21 operations),
      nephrectomy (9 operations). Surgery was performed in stages on each side, but
      unlike percutaneous operations, with discharge from the hospital. When using open
      surgery, only in 27 of the 47 patients complete discharge of kidney stones was
      achieved. A comparative analysis of single-step and stage surgery for bilateral
      SN revealed no significant difference in the duration of surgery and
      intraoperative blood loss (p > 0.1); endoscopic surgery compared with open
      surgery is characterized by significantly lower intraoperative blood loss and
      postoperative in-hospital stay (p < 0.001).

PMID- 24437247
TI  - [Laparoscopic transperitoneal and extraperitoneal reconstructive plastic surgery
      on the ureter].
AB  - The results of laparoscopic reconstructive operations on ureter distal of
      ureteropelvic junction are analyzed. The study included 19 patients with
      different obstructive lesions of the ureter who underwent surgery in the period
      from 2003 to 2012. According to the method of surgical treatment, the patients
      were divided into three groups. Ureteroureteroanastomosis was formed in 6
      patients, ureterocystoanastomosis--in 5 patients, and ureterolysis was performed
      in 8 patients. Mean duration of operations ranged from 113 to 210 minutes. There
      were no requirements of conversion to open surgery in any case. Significant blood
      loss and other intraoperative complications were not observed. It is concluded
      that laparoscopic reconstructive plastic surgery in these patients can be
      performed with good effect equal to open surgery.

PMID- 24437248
TI  - [Retroperitoneoscopic surgeries for pyoinflammatory diseases of the kidney with
      varying severity of endotoxemia].
AB  - The medical histories of 98 patients with pyoinflammatory diseases of the kidney,
      who underwent surgery by retroperitoneoscopic access, and 75 patients, who
      underwent traditional open surgery were analyzed. The degrees of multiple organ
      dysfunction and endotoxemia were determined in all patients. The groups were
      comparable in terms of clinical manifestations and severity of intoxication. The
      advantages of minimally invasive retroperitoneoscopic interventions are
      demonstrated; they allow to reduce the surgical morbidity, pain after surgery,
      the frequency and severity of intraoperative complications, length of in-hospital
      stay, the period of disability, the cost of treatment, and the need for
      medications.

PMID- 24437249
TI  - [Comparison of the results of correction of medium and proximal hypospadias using
      onlay island flap and tubularized incised plate methods in children].
AB  - Results of treatment of 35 children with primary medium and proximal hypospadias,
      including 15 boys undergoing Onlay Island Flap (OIF) and 20 boys undergoing
      Tubularized Incised Plate (TIP) were analyzed. At the time of OIF surgery the
      average age of children was 50.7 (14-130) months, TIP--26 (9-74) months. Long
      term outcomes (at least one year after surgery) were registered in all children.
      After OIF, complications were observed in 9 (60%) children; after TIP--in 5
      (25%). Statistically significant differences in the number of postoperative
      complications were not identified, but re-operation was statistically
      significantly less required in children undergoing TIP (p = 0.016).

PMID- 24437250
TI  - [Flexible approach to the appointment of solifenacin: for whom and when?].
AB  - Solifenacin at a dose of 5 mg per day has demonstrated the high efficacy in the
      treatment of patients with overactive bladder. However, for patients who remained
      dissatisfied with the outcome of treatment, the dose may be increased to 10. mg
      per day, which leads to the improvement of patient's condition. However, there is
      an opinion that treatment should be started with the use of high doses of the
      drug. Efficiency of solifenacin at a dose of 10 mg was accompanied by favorable
      safety and tolerability profile. Despite the fact that numerous studies have
      shown that the clinical efficacy of different anticholinergics is not very
      different from one another, it is known that patients may prefer some other
      drugs. Application of solifenacin in these patients leads to significant
      improvement in quality of life. Thus, flexible approach to the use of solifenacin
      allows to achieve the best results in the treatment of patients, including those
      cases where the initial treatment is not effective or is interrupted due to
      pronounced side effects.

PMID- 24437251
TI  - [Potentials for the combined therapy of urination disorders in men: the choice of
      optimal scheme of treatment].
AB  - Moderate to severe urination disorders occur in 13-29% of men, and their
      frequency increases progressively with age. The key for successful use of the
      capabilities of modern drug therapy is the understanding of the
      pathophysiological bases of urination disorders. Despite some successes of
      monotherapy with alpha-adrenoblockers and 5alpha-reductase inhibitors, combined
      use of drugs is appropriate, because the differences in mechanisms of action
      allows to simultaneously act on the smooth muscle tissue, causing its relax, and
      reduce the size of prostate by the induction of apoptosis, which ultimately
      allows to expect the maximum therapeutic effect. The goal of therapy in patients
      with BPH is not only a reduction in the severity of urination disorders, but the
      prevention of disease progression. Obviously, urination disorders in men are not
      always caused by an benign prostate hyperplasia. Hyperactive symptoms (primary
      and secondary, due to metabolic disorders in detrusor against the background of
      prolonged existence of bladder outlet obstruction) are revealed in significant
      proportion of men. In this cases, the use of M-anticholinergics is indicated.
      Administration of alpha-adrenoblockers and antimuscarinic drugs is one of
      potential variant of combined therapy. Thus, it is important to follow the
      principles of selectivity in patients with urination disorders. Modern
      pharmacotherapy has an arsenal of drugs, allowing to choose the drug therapy for
      patients with urination disorders depending on the prevalence of their types.

PMID- 24437252
TI  - [Contact ureterolithotripsy: updating and traditions].

PMID- 24437253
TI  - [Urological complications in oncogynecological patients].

PMID- 24437254
TI  - [Conservative an d surgical treatment of patients with tuberculosis of the
      bladder].

PMID- 24437255
TI  - [Hypogonadism and chronic obstructive pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is a systemic disease that affects
      not only the respiratory system. Sex hormones deficiency in men can be correlated
      with the COPD stages and make a negative contribution during its progression. Up
      to date, there are no long-term trials evaluating the effects of androgens on the
      parameters of respiratory function in patients with COPD. Changes of testosterone
      levels in patients with COPD correlate with forced expiratory volume, and
      hypoxemia and hypercapnia levels. Glucocorticosteroids exacerbate androgen
      deficiency in patients with COPD, and the use of hormone replacement therapy with
      testosterone in these patients is justified. Androgens, in particular drug
      nebido, testosterone depot, can be effectively used in treatment and
      rehabilitation of patients with COPD.

PMID- 24437256
TI  - [Explanatory diagrams of human circadian system].

PMID- 24437257
TI  - [Intercellular communication-based robust circadian oscillation of the
      suprachiasmatic nucleus in the brain: mechanisms beyond intracellular clock
      machinery].
AB  - Recent advances in circadian biology strongly suggest that there are still genes
      involved in the generation and maintenance of biological rhythms that remain to
      be identified. It has been generally appreciated that circadian rhythms are
      generated intracellularly through transcription/translation-based autoregulatory
      feedback circuits of the clock genes. However, the existence of new intracellular
      clock machinery that cannot be explained by existing clock genes has recently
      been reported. This clock manifests as oxidation-reduction cycles of
      peroxiredoxin proteins, implying that as-yet-undiscovered clock genes may exist
      within cells to regulate redox cycling. Moreover, great strides have also been
      made in understanding the cell-cell communication-based robust circadian
      oscillations of the suprachiasmatic nucleus (SCN), the central pacemaker in the
      brain. Thousands of neurons that constitute the SCN maintain a high degree of
      synchrony in a way that allows the SCN neurons to create coherent signals as a
      whole. Inactivation of the genes involved in the cell-cell synchronization of the
      SCN, which include the genes encoding VIP, VPAC2, and RGS16, leads to altered
      circadian rhythms in behavior and physiologies. The purpose of this review is to
      provide an overview of recent advances in the circadian biology, with a special
      emphasis on the importance of cell-cell interactions within the SCN.

PMID- 24437258
TI  - [Circadian rhythms in body temperature and sleep].
AB  - A 24 hour variation of core body temperature in humans is primarily regulated by
      the endogenous circadian pacemaker located in the suprachiasmatic nucleus. And
      the expression of circadian rhythm is modified by the thermoregulatory mechanism
      controlling heat production and heat loss, which also show circadian rhythms. On
      the other hand, circadian rhythms in sleep-wakefulness are expressed by two
      independent but mutually coupled oscillators, the circadian pacemaker and the
      oscillator specific to sleep-wakefulness. However, neither the mechanism nor the
      site of oscillation of the latter is known. The time cues for these two
      oscillators are different. They are usually but frequently uncoupled under free
      running conditions. Body temperature and sleep-wakefulness influence the
      counterpart in various extents, exerting masking effects on either circadian
      rhythm.

PMID- 24437259
TI  - [Circadian rhythm disruption and human development].
AB  - Ontogenetic developments of rest-activity, sleep-wakefulness, temperature and
      several hormone rhythms in humans were reviewed. The reported effects of
      environment on these alterations were also summarized. Then, disorders or
      conditions which often encounter during early stage of life and reveal circadian
      rhythm disruptions were described. These disorders or conditions included severe
      brain damage, visual disturbance, developmental disorders(autistic spectrum
      disorder and attention deficit/hyperactivity disorder), Rett syndrome, Angelman
      syndrome, Smith-Magenis syndrome, epilepsy, Yonaki, and inadequate sleep hygiene.
      Finally, it was emphasized that we should pay special attention on the
      development of youngsters who showed sleep disturbance during early stage of life
      with special reference to the later occurrence of developmental disorders.

PMID- 24437260
TI  - [Disrupted circadian rhythms and senescence].
AB  - Aging alters a broad spectrum of physiological, endocrine, and behavioral
      rhythms, and the close relationship between age-associated disease and disrupted
      circadian rhythms has been shown. Circadian rhythms are regulated by a set of
      clock genes and mutations in clock genes result in short life in animal models.
      The sirtuin family is involved in the regulation of many physiological functions,
      including gene transcription, energy metabolism, cell senescence and oxidative
      stress, and has recently been associated with regulation of circadian clock gene
      expression. Impaired circadian rhythmicity is related to a decrease of NO
      production with aging, suggesting the important role of NO for age-associated
      diseases. Furthermore, senescence decreases the ability of cells to transmit
      circadian signals to their clocks.

PMID- 24437261
TI  - [Chronotherapy--present and future].
AB  - Chronotherapy integrates chronoeffective and chronotoxic data to enhance an
      effectiveness and tolerance of a drug by choosing optimal dosing-time.
      Chronotherapy is already performed in several diseases such as hypertension,
      osteoporosis, dyslipidemia and malignant diseases, and improves the prognosis of
      these patients. However, it is still a new concept for physicians. Efforts are
      needed to take chronotherapy into dosage regimen by physicians, who have a major
      role in providing the benefits of chronotherapy to their patients. In addition,
      chronotherapy studies are not requested for drug evaluations by the regulatory
      authorities. However, preliminary screening of new drugs for their
      chronotherapeutic potential is a way of enhancing the research and development in
      pharmaceutical industries.

PMID- 24437262
TI  - [Circadian rhythm sleep disorder].
AB  - Primary pathophysiology of circadian rhythm sleep disorders(CRSDs) is a
      misalignment between the endogenous circadian rhythm phase and the desired or
      socially required sleep-wake schedule, or dysfunction of the circadian pacemaker
      and its afferent/efferent pathways. CRSDs consist of delayed sleep phase type,
      advanced sleep phase type, free-running type, irregular sleep-wake type, shift
      work type and jet lag type. Chronotherapy using strong zeitgebers (time cues),
      such as bright light and melatonin/ melatonin type 2 receptor agonist, is
      effective when administered with proper timing. Bright light is the strongest
      entraining agent of circadian rhythms. Bright light therapy (appropriately-timed
      exposure to bright light) for CRSDs is an effective treatment option, and can
      shift the sleep-wake cycle to earlier or later times, in order to correct for
      misalignment between the circadian system and the desired sleep-wake schedule.
      Timed administration of melatonin, either alone or in combination with light
      therapy has also been shown to be useful in the treatment of CRSDs.

PMID- 24437263
TI  - [Hypertension and circadian rhythm].
AB  - Abnormal circadian rhythm of blood pressure (BP), such as absent of nocturnal BP
      fall, higher sleep BP level and exaggerate morning BP surge, assessed by
      ambulatory BP monitoring have been reported to be associated with target organ
      damage and cardiovascular events independent of BP levels in hypertensive
      patients. It is clear that this abnormal circadian rhythm of BP is a risk of
      cardiovascular outcome, while it is not clear whether this abnormal circadian
      rhythm of BP is a maker as targeting hypertensive treatment independent of
      average BP levels. Although there are some intervention studies for this abnormal
      circadian rhythm of BP, it is not enough for constructive evidence.

PMID- 24437264
TI  - [Circadian clock disruption and diabetes mellitus].
AB  - Recent studies have demonstrated relationships between the dysfunction of
      circadian clocks and the development of obesity and type 2 diabetes. In humans,
      both shift work and the genetic variations of clock genes increase the risk of
      these disorders. In mice, the light conditions which induce chronic jet lag and
      modifications of the clock genes cause obesity and/or type 2 diabetes. Moreover,
      circadian clocks in peripheral tissues are impaired in both patients with type 2
      diabetes and genetically obese diabetic mice. Therefore, circadian clocks are
      important new therapeutic targets for preventing and treating obesity and type 2
      diabetes.

PMID- 24437265
TI  - [Dyslipidemia induced disorder of circadian rhythm].
AB  - Several epidemiological studies have suggested that the perturbation of circadian
      rhythm has adverse metabolic consequences (e.g., dyslipidemia) in humans. At the
      molecular level, circadian rhythms are encoded by an autoregulatory loop composed
      of a set of transcription activators (BMAL1/CLOCK) that induce expression of
      repressors (PER/CRY). The mammalian molecular clock is not only expressed within
      the master suprachiasmatic nucleus pacemaker neurons, but also within nearly all
      cells. In addition to this core loop, BMAL1/CLOCK also induce expression of the
      orphan nuclear hormone receptor, which modulates Bmal1 transcription. Disruption
      of clock genes results in metabolic deregulation in mice. In this article, the
      roles of clock genes in the regulation of metabolism were summarized based on the
      phenotypes of the knockout mice.

PMID- 24437266
TI  - [Circadian rhythm and ischemic heart disease].
AB  - Cardiovascular function exhibits circadian oscillation. Furthermore, the onset
      time and severity of cardiovascular diseases exhibit diurnal variation. The
      internal circadian clock whose center exists in the suprachiasmatic nucleus
      regulates this circadian variation. Many studies have reported that night shift
      workers have high risk of ischemic heart disease, suggesting a close association
      between cardiovascular diseases and circadian rhythm. In addition, recent studies
      obtained from genetically engineered mice with disrupted circadian rhythm have
      revealed that the circadian clock is closely related to the pathogenesis of
      cardiovascular diseases. Understanding the importance of circadian rhythm in the
      cardiovascular diseases will provide a novel chronotherapeutic approaches to the
      prevention and treatment.

PMID- 24437267
TI  - [Circadian rhythm and stroke].
AB  - Studies on the relationship between stroke incidence and alterations of circadian
      rhythm are scarce, while pathologically reduced or abolished circadian variation
      has been described to cause stroke since a long time ago. Although ischemic and
      hemorrhagic strokes are different entities and are characterized by different
      pathophysiological mechanisms, they share an identical pattern. A constellation
      of endogenous circadian rhythms and exogenous cyclic factors are involved. The
      staging of the circadian rhythms in vascular tone, coagulation balance including
      platelet function, and blood pressure plus temporal patterns in posture, physical
      activity, emotional stress, autonomic function, and medication effects play
      central and/or triggering roles. Features of the circadian rhythm of blood
      pressure, in terms of their chronic and acute effects on cerebral vessels, and of
      coagulation are especially important.

PMID- 24437268
TI  - [Headache].
AB  - Circadian rhythm has important implications in primary headache disorders.
      Migraine attacks are known to be triggered by either excess or lack of sleep.
      Cluster headache is clinically characterized by headache attacks that recur in
      chronologically similar patterns and the presence of the cluster period. Recent
      epidemiological data have disclosed that there is a tendency that migraine
      attacks occur during the daytime. A marked seasonal variation of attack frequency
      is noted in migraine with aura. Functional imaging and voxel-based morphometric
      assay revealed abnormalities in the hypothalamus in patients with cluster
      headache. Besides, the serum melatonin level is reduced in cluster headache. A
      polymorphism of the orexin receptor 2 gene has been identified as a risk factor
      for developing cluster headache. Orexin may be a key molecule closely implicated
      in both biological rhythm and nociception. As hypnic headache exhibits a strictly
      chronological pattern of headache attacks, this unique headache disorder is
      referred to also as "alarm clock headache". As with cluster headache, structural
      abnormalities of the hypothalamus have been detected by voxel-based morphometric
      assay. From the anatomical perspective, there are close fiber connections between
      the hypothalamus and the trigeminal nucleus caudalis, thus reinforcing the
      importance of diurnal rhythm disturbance in the pathophysiology of headache
      disorders.

PMID- 24437269
TI  - [Rheumatoid arthritis].
AB  - Although many requirements must be met to establish a diagnosis of rheumatoid
      arthritis (RA), morning stiffness is a characteristic feature of RA. Inflammatory
      cytokines show high concentrations in human blood and synovial fluid of RA, and
      excess production of these cytokines plays a central role in the pathogenesis of
      RA. The inflammatory cytokines in blood also show circadian rhythms peaking from
      midnight to early morning, which mirrors the timing of morning stiffness. In the
      treatment of RA, steroids are used to reduce pain and inflammation, and
      methotrexate are used prior to the development of destructive changes in bones,
      joints, and organ tissues. In this chapter, I would like to introduce the
      circadian rhythm of RA and the chronotherapies.

PMID- 24437270
TI  - [Chronotherapy of bronchial asthma].
AB  - Bronchial asthma is characterized by recurring symptoms, chronic inflammation of
      airway, reversible airflow limitation, and bronchial hyperresponsiveness. Lung
      function and symptoms of asthmatic patients frequently worsen between midnight
      and early morning. Currently, new drug delivery system based on
      chronopharmacology has been developed for the treatment of asthma. A night-time
      single dosing of anti-asthmatic drugs is clinically used for chronotherapy of
      asthma, which contributes to improve patient's adherence. This review focuses on
      chronotherapy of bronchial asthma.

PMID- 24437271
TI  - [Circadian regulation of urticaria and anaphylaxis].
AB  - IgE-mediated immediate-type allergic reactions in the skin show a diurnal rhythm,
      although the regulatory mechanisms are poorly understood. In mammals, the
      circadian rhythms are driven by the circadian clock system consisting of the
      light-entrained central clock located in the suprachiasmatic nucleus(SCN) of the
      hypothalamus and peripheral oscillators present in nearly all cell types. We have
      recently shown that the circadian clocks drive the daily rhythms of IgE-mediated
      allergic reactions in the skin by using a passive cutaneous anaphylactic reaction
      model in mice. We also found that systemic anaphylactic reaction shows a time of
      day-dependent variation, which relied on the circadian clocks. These findings
      highlight the circadian clocks as an important regulatory component of local and
      systemic allergic reaction.

PMID- 24437272
TI  - [Circadian chronotherapy for metastatic liver tumor].
AB  - Efficacy of circadian chronotherapy for liver metastases from colorectal cancer
      was evaluated. Chronomodulated infusion of anticancer drugs via the hepatic
      artery(HAI) was applied for patients with marginally resectable or unresectable
      liver metastases at initial diagnosis. Response rate of chemotherapy and
      frequency of liver resection after chemotherapy of patients treated with
      chronomodulated HAI were higher than those treated with flat HAI. Further,
      combination of chronomodulated regional HAI and systemic chemotherapy was the
      most effective prehepatectomy chemotherapy for the treatment of patients with
      advanced colorectal liver metastases. Based on these results, we are now
      performing phase II non-randomized open labeled trial of chronomodulated HAI with
      systemic administration of panitumumab for patients with such advanced liver
      metastases (ccFLAP trial). Circadian chronotherapy is an effective prehepatectomy
      chemotherapy for the treatment of patients with advanced and aggressive liver
      metastases from colorectal cancer.

PMID- 24437273
TI  - [Circadian rhythm and inflammatory bowel disease].
AB  - Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's
      disease (CD), is a chronic and recurrent inflammatory disorder of the intestinal
      tract. It has been demonstrated that sleep disturbances are involved in the
      pathogenesis of the patients with IBD. In addition, it has been shown that
      melatonin, which is a hormone produced by the pineal gland and maintains
      circadian rhythm, plays an important role as regulators of inflammation as well
      as a player in proper immune system and antioxidant system in the intestinal
      disorders. In this review, we present what is currently known regarding sleep
      disturbances and the role of melatonin in intestinal inflammation.

PMID- 24437274
TI  - [Circadian rhythm and mood disorder].
AB  - Mood disorders show a common feature of distorted cycling of biological systems,
      manifesting, for example, as diurnal mood variation in depression, phasic time
      course in bipolar disorder, and seasonal mood swing in seasonal affective
      disorder. Accordingly, circadian dysfunction has been supposed to play an
      etiological role in mood disorders. Increasing evidence indicates that circadian
      misalignment between neuroendocrinological rhythm and the timing of sleep
      correlates with the severity of symptoms. In addition, several genetic studies
      have suggested that certain clock gene variants play a role in vulnerability to
      these disorders, and especially bipolar disorders. However, the role of circadian
      phenotypes and circadian genes in mood spectrum disorders remains unclear,
      although currently seem to have a pathoplastic rather than a pathogenetic effect.

PMID- 24437275
TI  - [Autism spectrum disorders].

PMID- 24437276
TI  - [Nocturia and the circadian rhythm].
AB  - Nocturia, undesired micturition at night, is present in 60% to 90% of individuals
      older than 60 years and causes significant deterioration in quality of life.
      Prevention of micturition at night is regulated by a triad of factors including
      decreased arousal in the brain, decreased urine production rate in the kidneys
      and increased functional bladder capacity. There is increasing evidence that the
      triad of micturition is modulated by the circadian clock system. Risk factors of
      nocturia such as hypertension, cardiovascular diseases, diabetes mellitus,
      cerebrovascular accidents and depression have also been associated with
      dysfunction of the circadian clock system. The etiology of nocturia might be
      elucidated by investigating it as dysfunction of peripheral or central circadian
      clock.

PMID- 24437277
TI  - [Importance of NAMPT-mediated NAD-biosynthesis and NAD-dependent deacetylase
      SIRT1 in the crosstalk between circadian rhythm and metabolism].
AB  - Circadian rhythms are generated by well-conserved interlocked transcriptional
      feedback loops that involve clock genes. A growing body of research suggests that
      there is biological crosstalk between circadian rhythm and metabolism. We
      recently found that the key NAD biosynthetic enzyme, nicotinamide
      phosphoribosyltransferase (NAMPT), and NAD-dependent deacetylase SIRT1 play a
      critical role in such crosstalk, by creating a novel feedback loop in which NAD
      functions as a "metabolic oscillator". This review aims to summarize recent
      progress in elucidating the pathophysiological importance of clock genes, NAMPT
      mediated NAD biosynthesis, and SIRT1, in the crosstalk between circadian rhythm
      and metabolism.

PMID- 24437278
TI  - [Chrono-nutrition and chrono-exercise].
AB  - The circadian rhythm controls many physiological functions, such as feeding,
      motor activity, endocrine secretion and autonomic nerve. Regular feeding pattern
      can entrain the peripheral circadian clock, whereas peripheral clock systems can
      control the absorption distribution, metabolism and excretion of nutrients,
      suggesting mutual interactions between circadian clocks and nutrition/food. The
      interactions were so-called by "chrono-nutrition", and bigger meals for breakfast
      were good for entrainment of peripheral clock and protection of obesity. Similar
      to chrono-nutrition the timing of exercise ("chrono-exercise") is important for
      both entrainment signals and energy expenditure. Evening exercise and/or feeding
      then exercise was good timing exercise for protection of obesity. Taken all, it
      is suggested that timing of feeding and exercise is now one of key factors for
      metabolic syndrome.

PMID- 24437279
TI  - [Chrono-drug delivery system based on the circadian rhythm of transferrin
      receptor].
AB  - Transferrin receptor 1(TfR1) is a key cell surface molecule that regulates the
      uptake of iron-bound transferrin. TfR1 expression is higher in tumor cells than
      in normal cells. Thus, intracellular targeting using iron-saturated Tf as a
      ligand for TfR-mediated endocytosis has attracted attention. TfR1 in colon cancer
      bearing mice exhibits a 24-hour rhythm in mRNA and protein levels. The clock
      controlled gene c-MYC rhythmically activate the transcription of the TfR1 gene.
      In addition, the cyclical accumulation of TfR1 causes dosing time-dependent
      changes in the intratumoral delivery of drug by receptor-mediated endocytosis.
      Identification of the circadian properties of molecules that are targeted by
      ligand-directed DDS may aid the choice of the most appropriate time of day for
      their administration.

PMID- 24437280
TI  - [Cancer and lifestyle-related diseases risk among shifts workers].
AB  - Shift work is unavoidable and roughly 15-20% of workers are estimated to work on
      shift schedules worldwide. On 2007, the International Agency for Research on
      Cancer (IARC) panel concluded that shift work that involves circadian disruption
      is probably carcinogenic in humans. The risk has become a growing concern of
      public health. Shift work could not be exterminated though, there are possible
      protective measures; such as a nap system during night work to modulate burden of
      night work, and breast cancer screening program among female shift workers for
      early detection of the disease. This paper reviews current evidence on that risk
      and points out contentions for the risk communication.

PMID- 24437281
TI  - [Current status and perspectives of the research in Pendred syndrome].
AB  - Pendred syndrome is an autosomal recessive disorder characterized by
      sensorineural hearing loss, goiter, and a partial defect in iodide
      organification, and is the most common syndromic hearing loss. Hearing loss is
      congenital in most cases and is accompanied by an enlarged vestibular aqueduct
      and a Mondini cochlea. Pendred syndrome and autosomal recessive deafness-4
      (DFNB4) with enlarged vestibular aqueduct comprise a phenotypic spectrum caused
      by mutations in SLC26A4. Recently, mutations in FOXI1 and KCNJ10 have also been
      identified in DFNB4. Molecular mechanism of hearing loss and goiter remains to be
      elucidated, and therapies which can reverse or prevent the progression of the
      symptoms are not available. Here, we describe advances in the basic, clinical,
      and translational studies on Pendred syndrome.

PMID- 24437282
TI  - [Further characterization between oral bisphosphonate dosing interval and patient
      preference--patient preference for daily, weekly and monthly bisphosphonate,
      based on results of 3,052 outpatients questionnaires].
AB  - This single center questionnaire survey began in 15 February 2013 and ended in 31
      May 2013 at our clinic. Patients were received the questionnaire to measure
      preference about bisphosphonate preparations (BPs). The questionnaire consisted
      of the following two questions: [which do you prefer once-daily, once-weekly or
      once-monthly bisphosphonate? why do you prefer any one?]. We studied 3,052
      outpatients (822 male and 2,230 female) aged 63.7 +/- 18.0 years, had had various
      orthopedic diseases, including osteoporosis. Thirteen hundred and thirty four
      patients (43.7%) preferred once-weekly BPs. Once-monthly BPs and once-daily BPs
      were ranked second and third, 926 patients (30.3%) and 750 patients (24.6%),
      respectively. The dominant reasons for preferring once-weekly BPs, once-monthly
      BPs, and once-daily BPs, were "once-daily dosing schedule is troublesome, but,
      once-monthly dosing schedule tends to forget", "once-monthly dosing schedule is
      more convenient", and "it is hard to forget dosing by once-daily dosing
      schedule", respectively. Of 93 patients had already taken once-daily BPs, 62
      patients (66.7%) preferred once-daily BPs. Of 672 patients had already taken once
      weekly BPs, 419 patients (62.4%) preferred once-weekly BPs. Of 48 patients had
      already taken once-monthly BPs, 40 patients (83.3%) preferred once-monthly BPs.
      Patients tended to prefer BPs that were already administered. Three hundred and
      five patients were randomly assigned to switch from current osteoporosis medicine
      to once-monthly risedronate for two months, and these patients were received the
      questionnaire before and after the treatment period. The rate of preferring once
      monthly BPs significantly increased from 39.0% to 81.0%, after taking once
      monthly risedronate for two months. Therefore, these results revealed that
      patient preference for oral bisphosphonate dosing interval was varied. It was
      concluded that risedronate was useful for various patients, because it had once
      daily, once-weekly, and once-monthly preparations.

PMID- 24437283
TI  - [Adult orthodontic technique: development and challenge].
AB  - Orthodontic treatments have increasingly become accepted by adults. However, the
      treatment therapies and philosophies for adults and adolescents have numerous
      differences. Orthodontic treatment for adults requires more careful planning,
      flexible management, interdisciplinary cooperation, and rational expectations.
      New techniques, such as mini-screw implants, invisalign, and self-ligating
      brackets, have recently been used to update treatments and widen the application
      of adult orthodontics by improving the treatment results. However, orthodontists
      still face a number of risks and challenges.

PMID- 24437284
TI  - [Three-dimensional finite element analysis of the effect of the location and
      diameter of implants on the stress distribution in three-unit implant-supported
      posterior cantilever fixed partial dentures under dynamic loads].
AB  - OBJECTIVE: To examine the effect of the location and diameter of implants on
      stress distribution in three-unit implant-supported posterior cantilever fixed
      partial dentures (FPD) in the mandible. METHODS: A three-dimensional finite
      element model was developed to represent a rigid implant-supported posterior FPD
      that restores the second left premolar, first molar, and second molar. The
      location of the distal implant with a diameter of 4.8 mm remained the same,
      whereas the mesial implants with diameters of 4.1 and 4.8 mm were successively
      moved toward the posterior area with distances of 5.5, 8.0, 10.5, and 13.0 mm
      from the long axis of the mesial implants to the first premolar to form the
      cantilever FPD. Dynamic loads of 250 N were applied from different directions on
      the buccal and lingual cusps of the FPD to simulate the masticatory cycle for
      0.875 s. The maximum Von Mises stresses were calculated using the finite element
      analysis software MSC. Marc and Partran. RESULTS: The maximum Von Mises stresses
      of the mesial and distal implants increased to some extent as the mesial implants
      moved toward the posterior area. Significant increases in the maximum Von Mises
      stresses were obtained when the mesial implants were located more than 8.0 mm
      posterior to the first premolar, and moderate increases in the stresses were
      observed when the mesial implants were located less than 8.0 mm posterior to the
      first premolar. The use of a broader implant reduced the stress on the interface
      between the bone and the implants. The maximum Von Mises stresses were found in
      the cervical region of the cortical bone adjacent to the mesial or the distal
      implants during stages II to IV of the masticatory cycle. Off-axial loading
      induced more stresses compared with vertical loading. CONCLUSION: The location of
      implants in three-unit implant-supported posterior cantilever FPD is a
      significant factor that influences the stress generated in the interface between
      the bone and the implants. An implant-supported cantilever FPD is a feasible
      option for restoring missing teeth when the length of the cantilever is not
      greater than the width of a premolar. Two important factors should be considered
      before choosing the implant diameter, namely, bone volume and cantilever length.

PMID- 24437285
TI  - [Mini-implant stability analysis at different healing times before loading].
AB  - OBJECTIVE: This study aims to biomechanically analyze a mini-implant at different
      healing times before loading. METHODS: Sixty-four mini-implants with (12 +/- 1) N
      x cm insertion torque were placed in the low jaw of eight beagle dogs. The test
      mini-implants remained in the low jaw for 0, 1, 3, and 8 weeks of bone healing
      and for an additional 10 weeks under a force of 0.98 N. The unloaded control
      implants were further divided into four groups (1, 3, 8, and 10 weeks). Maximum
      removal torque (MRT) testing was performed to evaluate the interfacial share
      strength of each group. Surface analysis of the removed implants was performed by
      scanning electric microscope (SEM). RESULTS: The MRT for the loading implants at
      0, 1, 3, and 8 weeks of healing were 4.10, 4.25, 2.42, and 4.42 N x cm,
      respectively. During the healing process, the removal torque values of the 3-week
      implants were significantly lower than those of the other healing groups (P <
      0.05). The unloaded 3-week implants also had lower removal torques (P < 0.05).
      The implant surface of the 3-week test group showed more fibrous bone. However,
      the other loading implants had more lamellar-like tissue. CONCLUSION: A stable
      dangerous period occurred approximately 3 weeks after mini-implant insertion. A 3
      week healing is disadvantageous to the stability of the implant. Orthodontics
      loading occurred immediately or after 1 week as a function of the healing time.
      The 8-week implant appeared to have a positive effect on peri-implant bone
      remodeling and implant stability.

PMID- 24437286
TI  - [Effects of post-cure heat treatment on the bond strength of ceramage composite
      resins for titanium casting using different surface treatments].
AB  - OBJECTIVE: This study aims to investigate the effects of post-cure heat treatment
      (PCHT) on the bond strength of Ceramage composite resins for titanium casting
      using different surface treatments. METHODS: Metal specimens (n=30) were randomly
      divided into following five groups: polishing (group A), sandblasting (group B),
      acid etching after sandblasting (group C), PCHT after sandblasting (group D), and
      PCHT after sandblasting and acid etching (group E). The specimens were then
      processed and coated with Ceramage composite resins according to the grouping.
      After treatment, the shear bond strengths and microhardness of the specimens were
      evaluated. The fracture surface morphology of the titanium-Ceramage composite
      resin was observed using a scanning electron microscope. RESULTS: The shear bond
      strengths of groups A to E were (5.92 +/- 0.54), (10.25 +/- 0.55), (14.97 +/-
      0.88), (14.41 +/- 0.63), and (19.95 +/- 0.52) MPa, respectively. No statistical
      difference was found between groups C and D, whereas the rest of the groups
      showed statistically significant differences (P < 0.01). Visible polymerization
      residues were found on titanium porcelain metal surface of groups B to E. The
      microhardness values of groups D and E were higher than those of groups B and C
      (P < 0.05). CONCLUSION: PCHT significantly improves the bond strength and surface
      microhardness of Ceramage composite resins for titanium casting.

PMID- 24437287
TI  - [Study on the function of keratinocyte growth factor on apoptosis of oral mucosal
      epithelial cells].
AB  - OBJECTIVE: To study the function of keratinocyte growth factor (KGF) on apoptosis
      of oral mucosal epithelial cells and to provide a basis for further investigation
      of the role of KGF in the occurrence and development of oral mucosal diseases.
      METHODS: Different concentrations of KGF (control group, 0 ng x mL(-1);
      experiment 1 group, 5 ng x mL(-1); experimental 2 group, 25 ng x mL(-1);
      experiment 3 group, 50 ng x mL(-1)) were added in oral mucosa epithelial cells
      cultured in vitro. After training for 12, 24, and 48 h, cell morphology was
      observed under an inverted microscope. Apoptosis was detected by using a flow
      cytometry instrument, and mRNA expression of apoptosis-related genes Bcl-2 and
      Bax was detected by using Real-Time fluorescent quantitative detection. RESULTS:
      Cell adherence of the experimental group was more obvious than that of the
      control group, and the cell nucleolus of the experiment 3 group was obviously
      cultured at 48 h. After culturing for 48 h, the apoptosis rate and Bcl-2 and Bax
      mRNA expression among the four groups were statistically significant. The
      increase of KGF concentration, apoptosis rate, and Bax mRNA expression gradually
      reduced, whereas Bcl-2 mRNA expression increased (P < 0.05). CONCLUSION: KGF may
      inhibit epithelial cell apoptosis through upregulation of Bcl-2 mRNA and
      downregulation of Bax mRNA.

PMID- 24437288
TI  - [Effect of hot chemical etching on bond strength of zirconia to resin].
AB  - OBJECTIVE: This study aims to evaluate the influence of hot chemical etching on
      short- and long-term shear bond strength (SBS) of zirconia to resin. METHODS:
      Eighty zirconia ceramic slices were obtained and randomly divided into five
      groups based on the surface treatment to be applied--group A: H2SO4/(NH4)2SO4 hot
      solution etching + application of Clearfil; group B: HF/HNO3 hot solution etching
      + application of Clearfil; group C: H2SO4/HF/HNO3 hot solution etching +
      Clearfil; group D: alumina sandblasting + application of Clearfil; group E:
      tribochemical silica coating + application of silane coupling agent. Eighty
      composite cylinders were bonded to pretreated ceramic slices using a bis-GMA
      based resin cement. Specimens in each group were divided into two fractions: the
      first half received 24 h water storage, and the second half received 40 d water
      storage. Then, SBS tests were conducted. Morphological analysis of sandblasted
      alumina and hot chemical-etched zirconia surfaces were performed by scanning
      electron microscopy(SEM). RESULTS: Group E displayed the highest SBS before
      artificial aging, and no statistical difference was found among the other groups.
      After 40 d water storage, groups A, B, and E showed significantly higher SBS than
      groups C and D. SBS increased significantly after artificial aging in groups A
      and B. No significant variations were found before and after artificial aging in
      the other groups. CONCLUSION: The experimental hot chemical etching solution
      provides enhanced bonding for zirconia than sandblasting, and the bond strengths
      remain stable after artificial aging.

PMID- 24437289
TI  - [Foundation of the interactive oral and maxillofacial radiological image
      annotation database].
AB  - OBJECTIVE: This project aims to establish an interactive oral and maxillofacial
      radiological image annotation database and to analyze its feasibility for
      implementation into curricula in order to develop a highly effective software for
      image browsing. METHODS: We established the interactive image annotation database
      primarily on the basis of the local network and Foxit Reader. A pilot survey was
      then conducted to determine the performance of the interactive database. Seventy
      six students were asked to complete a structured and open questionnaire related
      to their perceptions of using the database. Simple numeric quantitative and
      qualitative analyses were then applied. RESULTS: A total of 542 portable document
      format (PDF) digital teaching images and corresponding annotated files were
      collected. The survey revealed that most of the students found the database
      useful. Approximately 87.50% of the 64 subjects who compelete questionnaire
      believed that the database was superior to an older system (joint photographic
      experts group, JPEG) of image browsing. CONCLUSION: The integration and sharing
      of teaching resources and the establishment of an internet-based learning
      platform is the key to realizing a digital medical teaching system. The
      established database has high potential in a wide range of practical
      applications.

PMID- 24437290
TI  - [Fissure morphology and caries prevalence in the first permanent molars of
      children in the Dalian development area].
AB  - OBJECTIVE: This study aims to determine the fissure morphology, prevalence, and
      severity of caries in the first permanent molars of 7-year-old to 9-year-old
      children in the Dalian development area. The study also aims to investigate the
      relationship between fissure morphology and noncavitated lesions. METHODS: A
      multi-stage, cluster sampling method was used. Three schools were randomly
      selected from 20 elementary schools in the Dalian development area. All of the
      children in the selected schools completed clinical oral examinations. A
      diagnosis criterion of the International Caries Detection and Assessment System
      was used to assess the cavitated and noncavitated dental caries in the first
      permanent molars. Fissure depth and fissure stain were also assessed. RESULTS:
      The total size of the study sample was 1 160. The prevalence of cavitated caries
      was 19.1%, and the mean D3-6FT score was 0.31. No significant differences were
      found between urban and rural subjects, between men and women, and among
      different age groups. The prevalence and D1-2FT score of noncavitated caries were
      42.1% and 0.86, respectively. The D1-2FT score for rural children was
      significantly higher than that for urban children, and the D1-2FT score for girls
      were higher than that for boys. No statistical differences were found among
      different age groups. The prevalence of deep fissures in the first permanent
      molars was 44.7%. The prevalence of noncavitated caries increased with increasing
      fissure depth. CONCLUSION: The prevalences of noncavitated caries and deep
      fissure in the first permanent molar of 7-year-old to 9-year-old children in
      Dalian were high. Fissure morphology was found to be related to noncavitated
      caries.

PMID- 24437291
TI  - [Perioperative nursing of internal sinus floor elevation surgery with
      piezosurgery].
AB  - OBJECTIVE: This study aims to summarize the nursing experience in the internal
      sinus floor elevation surgery with piezosurgery. METHODS: The medical records of
      48 patients who underwent sinus floor elevation surgery with piezosurgery in the
      Department of Implantation, West China Hospital of Stomatology, Sichuan
      University, were reviewed. The preoperative, intraoperative, and postoperative
      nursing methods were summarized. RESULTS: All 48 patients underwent smooth
      surgeries and did not encounter complications. CONCLUSION: Careful preoperative
      preparation, careful and meticulous intraoperative nursing cooperation, and
      provision of sufficient health education after surgery to the patients are the
      key factors that ensure the success of internal sinus floor elevation surgery
      with piezosurgery.

PMID- 24437292
TI  - [Assessment of occlusal vertical dimension using angles: a pilot study].
AB  - OBJECTIVE: This study aims to identify highly accurate quantitative methods for
      evaluating the occlusal vertical dimension by using cephalometric radiographs to
      analyze the craniofacial hard tissue landmarks in 30 cases with normal
      occlusions. METHODS: A total of 30 subjects with normal occlusions and aged
      between 20 and 30 years old were included in the study. Cephalometric radiographs
      were obtained and analyzed using the Winceph 8.0 measurement software. Landmark
      points were identified and measured. RESULTS: The mean distribution difference of
      the center angle (CA) and lower angle (LA) of the face was not statistically
      significant (t = -1.490, P = 0.147). The CA and LA had a significantly linear
      correlation (r = 0.976, P = 0.000), and the regression equation was y = 0.298 +
      0.997x. CONCLUSION: The CA can be used to assess and quantify the occlusal
      vertical dimension in clinical practice.

PMID- 24437293
TI  - [Application of cone-beam computed tomography in the diagnosis and treatment of
      external root resorption of adjacent teeth caused by impacted teeth].
AB  - OBJECTIVE: This study aims to investigate the diagnosis and treatment of external
      root resorption of adjacent teeth caused by impacted teeth via cone-beam computed
      tomography (CBCT). METHODS: A total of 19 teeth from 15 patients with uncertain
      external root resorption caused by an adjacent impacted tooth were examined from
      January 2011 to December 2011. All teeth with uncertain external root resorption
      were scanned by CBCT. Three dimensions reconstruction were the conducted to
      determine the location and extent of resorption. RESULTS: In all cases, CBCT
      identified the accurate location and extent of external root resorption caused by
      adjacent impacted teeth. Furthermore, the technique provided impacted teeth
      location in three dimensions, including the relation between the impacted teeth
      and surrounding vital structures. CONCLUSION: CBCT can provide direct and
      accurate images of the location and extent of external root resorption, as well
      as the location of the adjacent impacted teeth in three dimensions. Therefore,
      the proposed technique provides reliable information for clinical diagnosis and
      treatment.

PMID- 24437294
TI  - [Minocycline hydrochloride liposome controlled-release gel improves rat
      experimental periodontitis].
AB  - OBJECTIVE: To evaluate the therapeutic effects of 2% minocycline hydrochloride
      liposome controlled-release gel on the periodontitis in an established rat
      periodontitis model. METHODS: Biocompatibility was tested by oral perfusion
      sample solution for long-term observation. Minocycline hydrochloride liposome
      controlled-release gel was utilized to treat the established rat periodontitis
      model. The rats were selected randomly and divided into three groups: group A
      (PERIO-treated group), group B (minocycline hydrochloride liposome controlled
      release gel treated group), and group C (negative control group). The gingival
      index (GI) and probing depth (PD) were detected, and the number of mononuclear
      and broken bone cells were examined after 7, 14, 28, and 56 d. RESULTS: The
      minocycline hydrochloride liposome controlled-release gel exhibited excellent
      biocompatibility based on weight measure and tissue section evaluation. The rats
      with periodontitis demonstrated that GI, PD, and the number of mononuclear and
      broken bone cells of group B decreased in 14, 28, and 56 d. Pathological
      observation showed that new bones and fibers were formed in group B. CONCLUSION:
      Minocycline hydrochloride liposome controlled-release gel improves rat
      periodontitis, thereby providing valuable evidence for clinical application.

PMID- 24437295
TI  - [Effect of infiltration resin on the color masking of labial enamel white spot
      lesions].
AB  - OBJECTIVE: To evaluate the effect of infiltration resin on masking white spot
      lesions by assessing the change in the white spot area. METHODS: Seventy-four
      maxillary anterior teeth with post-orthodontic decalcification teeth were
      investigated in this study. All teeth were treated with infiltration resin
      according to manufacturer recommendation. Standardized digital images were taken
      before, immediately after, and one week after treatment. The results were
      classified into three groups: com-pletely masked, partially masked and unchanged.
      The images of partially masked teeth were analyzed using an image analysis
      software. The size of the white spot lesion (W) and the whole-tooth facial
      surface (T) were measured, and the W:Tratio (%) was calculated. Statistical
      evaluation of the lesions was performed using Kruskal-Wallis and Mann-Whitney
      tests. RESULTS: Among the 74 teeth, 20 (27%) teeth were classified as completely
      masked and 54 (73%) teeth were classified as partially masked; no tooth was
      unchanged. The W:T ratio significantly decreased from 39.28% before treatment to
      9.46% after treatment (P < 0.05). CONCLUSION: Resin infiltration is an effective
      treatment for masking white spot lesion. However, the masking effect depends on
      the lesion depth and activity.

PMID- 24437296
TI  - [Evaluation of root resorption after palatal expansion by magnetic expansion
      appliance].
AB  - OBJECTIVE: To investigate the root length of posterior teeth after palatal
      expansion by magnetic expansion appliance. METHODS: A total of 32 patients who
      accepted palatal expansion with magnetic expansion appliance were enrolled in the
      study. Pretreatment and post-treatment cone-beam computed tomography (CBCT)
      images were obtained. A paired t test was used to evaluate the length change, and
      a group t test was used to compare the tooth lengths of developing and developed
      teeth. RESULTS: Anchorage teeth showed greater root resorption than non-anchorage
      teeth, whereas the developed posterior teeth showed reduced resorption. Moreover,
      the mesial buccal roots of the first molar and first premolar were reduced. No
      resorption was found in the developing teeth group. CONCLUSION: The magnetic
      palatal expansion can reduce the root length, particularly of developed root. The
      developing root of anchorage teeth show greater tolerance to resorption than the
      developed root. Early palatal expansion treatment with magnetic expansion
      appliance can reduce the risk of root resorption.

PMID- 24437297
TI  - [Three-dimensional evaluation of the relationship between dental and basal arch
      forms in skeletal class II malocclusions].
AB  - OBJECTIVE: This study aims to investigate the relationship between the dental and
      basal arch forms of patients with skeletal class II malocclusion using three
      dimensional virtual models and to generate the best-fit curve for these arch
      forms. METHODS: The mandibular dental casts of 35 skeletal class II patients were
      taken prior to treatment and were laser scanned. The facial axis (FA) points,
      which were used to represent the dental arch, and the WALA points, which were
      used to represent the basal bone, were identified for each tooth from the right
      first molar to the left first molar. The Pearson correlation coefficients between
      the intercanine and intermolar widths at the FA and WALA points were determined.
      Finally, the best-fit curves were generated using the fourth-degree polynomial
      equation to represent the arch forms. RESULTS: A strong correlation was found
      between the FA and WALA intermolar widths (r = 0.873). However, a moderate
      correlation was observed between the FA and WALA intercanine widths (r = 0.534).
      The difference between the intermolar widths at the FA and WALA points was
      significant (P < 0.01). No statistically significant difference was found between
      the intercanine widths (P = 0.481). The radii of curvature of the FA and WALA
      curves in the anterior teeth area were 15.194 and 20.250, respectively. The
      regression coefficients of the FA and WALA curves were calculated as R2 = 0.912
      and 0.947, respectively. CONCLUSION: For skeletal class II malocclusion patients,
      the FA and WALA dental intermolar widths showed strong correlation, whereas the
      FA and WALA intercanine widths exhibited moderate correlation. The FA points were
      located more labially in the anterior teeth area but more lingually in the
      posterior teeth area. No statistically significant difference was found between
      the intercanine FA and WALA widths. The difference between the intermolar widths
      at the FA and WALA points was significant. The radii of curvature of the FA curve
      was larger than that of the WALA curve in the anterior teeth area.

PMID- 24437298
TI  - [Cone-beam CT evaluation of the changes in the temporomandibular joint of
      patients with class II division 1 subdivision malocclusion before and after twin
      block treatment].
AB  - OBJECTIVE: This study aims to evaluate the temporomandibular joint (TMJ) changes
      in patients with class II division 1 subdivision malocclusions before and after
      Twin-block treatment using a cone-beam CT (CBCT). METHODS: Twenty subjects with
      class II division 1 subdivision malocclusions were included in this study. Hand
      wrist radiographs were conducted in the FG-G stage. CBCT was performed to
      determine the changes in the TMJ before and after the Twin-block treatment. The
      InVivoDental software was used to calculate the relevant parameters from the
      three-dimensional CBCT images. The acquired data were then analyzed. RESULTS:
      After treatment, the sagittal condylar anterior spaces were reduced, whereas the
      sagittal condylar superior and posterior spaces as well as the coronal condylar
      superior space increased (P < 0.01). The condylar height, sagittal condylar
      angles, and condylar anteroposterior diameters also increased (P < 0.01).
      CONCLUSION: After the Twin-block treatment, new bone deposition was observed on
      the condyle. The condyle height also increased and resulted in adjustments in the
      condyle position within the glenoid fossa to more downward and forward positions.
      CBCT can quantify TMJ changes and provide an objective assessment to orthodontic
      treatment.

PMID- 24437299
TI  - [Exploring the relationship between secreted frizzled-related protein 1 and
      chronic periodontitis].
AB  - OBJECTIVE: This study detects the expression of secreted frizzled-related protein
      1 (SFRP1) in healthy patients and patients with chronic periodontitis (CP) and
      explores the relationship between SFRP1 and the occurrence and development of CP.
      METHODS: First, 28 patients forming the CP group were further divided into mild,
      moderate, and severe CP subgroups according to clinical attachment loss (CAL)
      data. Ten healthy volunteers were recruited in the control group. Gingival
      crevicular fluid (GCF) was collected from all of the patients, and the
      concentration of SFRP1 in the GCF samples was detected using enzyme-linked
      immunosorbent assay. Next, gingival lesions were obtained from 22 patients in the
      CP group and healthy gingival tissues were obtained from the 10 healthy patients
      in the control group. Immunohistochemical analysis for SFRP1 was used to analyze
      the correlation between the expression of SFRP1 and the severity of CP based on
      staining intensities. RESULTS: The concentration of SFRP1 in GCF samples taken
      from of the CP group (281.07 ng x L(-1) +/- 33.37 ng x L(-1)) was significantly
      higher than that in samples taken from the control group (245.30 ng x L(-1) +/-
      35.69 ng x L(-1)) (P < 0.05). A significant positive correlation was observed
      between the concentration of SFRP1 in GCF and CAL (r = 0.651, P < 0.001).
      Furthermore, the SFRP1 scores in the CP groups (4.500 +/- 0.913) were
      significantly higher than those in the control group (2.800 +/- 1.135) (P <
      0.001). SFRP1 scores did not vary significantly among the CP subgroups (P >
      0.05). CONCLUSION: SFRP1 expression in the CP groups was significantly higher
      than that in the control group. Thus, SFRP1 may play a significant role in the
      development of CP.

PMID- 24437300
TI  - [Quantitative analysis of streptococcus mutans and its proportion in the dental
      plaque of different caries-susceptible children].
AB  - OBJECTIVE: To determine the quantity of Streptococcus mutans (S. mutans) and the
      ratio of S. mutans to total bacteria in the dental plaque of different caries
      susceptible children. METHODS: Dental plaque samples from 26 children aged 3
      years old to 4 years old were collected. The quantities of S. mutans and total
      bacteria were determined by TaqMan real-time fluorescence quantitative polymerase
      chain reaction (PCR). The ratio ofS. mutans to total bacteria in children with
      and without caries was calculated and statistically analyzed. RESULTS: In
      children with and without caries, the quantities of S. mutans were 1.33 x 10(5)
      and 1.16 x 10(3) CFU x mg(-1), the total bacteria were 7.17 x 10(7) and 1.01 x
      10(8) CFU x mg(-1), and the ratios of S. mutans to total bacteria were 0.058 6
      and 0.018 6, respectively. Significant differences were observed in the
      quantities of S. mutans and the total bacteria as well as in the ratios of S.
      mutans to total bacteria of the two groups (P = 0.033, 0.418, 0.008). CONCLUSION:
      The quantities of total bacteria of the two groups show negligible difference.
      However, the quantity of S. mutans and the ratio of S. mutans to total bacteria
      in caries-susceptible children are higher than those in caries-free children.
      Therefore, the ratios of S. mutans to total bacteria in plaque are closely
      associated with the prevalence of dental caries in children.

PMID- 24437301
TI  - [Impression technique with a tissue-stop area for type four edentulous jaws].
AB  - OBJECTIVE: This study aims to develop a mandibular impression technique for type
      four edentulous jaws. METHODS: Twenty patients with type four edentulous jaws
      were selected for this study. The mandibular impression for each patient was made
      using both a traditional impression technique and the impression technique with a
      tissue-stop area. After the cast was made for each impression, the temporary
      denture bases were constructed on each cast. When the patients wear temporary
      denture bases, they must appreciate the degree of comfortability provided by each
      denture base. Whether the soft tissues that had been pushed away was also
      recorded. For 10 of the randomly selected patients, a complete denture was made
      using the traditional impression technique; the remaining ten subjects were given
      complete dentures constructed by the impression technique with a tissue-stop
      area. The number of times a review for misfit was recorded. The tissue fitness of
      each denture was also recorded. RESULTS: A paired t-test showed that the soft
      tissues that stacked on the residual ridge were more readily pushed away by the
      impression technique with a tissue-stop area than by the traditional impression
      technique. However, for all patients, the degree of comfortability did not vary
      when different techniques were used. The independent t-test results indicated
      that the differences between the fitness of dentures constructed using different
      impression techniques were not significant. The number of times a review for
      misfit conducted by the impression technique with a tissue-stop area was
      considerably lower than that for patients wearing traditionally dentures.
      CONCLUSION: Using the impression technique with a tissue-stop area can more
      readily push away the soft tissues packed on the residual ridge and reduce the
      times of review for misfit compared with using the traditional technique.
      However, the degree of comfortability and fitness of denture are not improved.

PMID- 24437302
TI  - [Effects of estrogen on the proliferation and differentiation of human embryo
      mandibular condylar chondrocytes].
AB  - OBJECTIVE: To determine the effects of different estrogen concentrations on the
      proliferation and differentiation of human embryo mandibular condylar
      chondrocytes (MCCs). METHODS: In vitro-cultured MCCs were incubated and treated
      with estrogen at different concentrations. The MCCs were identified by toluidine
      blue and type II collagen immunocytochemical methods, and cell proliferation was
      monitored using methyl thiazolyl tetrazolium assay. RESULTS: The addition of 10(
      12) or 10(-6) mol x L(-1) exogenous estrogen inhibited the growth of MCCs,
      whereas addition of 10(-10) or 10(-8) mol x L(-1) exogenous estrogen promoted
      growth. These estrogen effects were time-dependent. CONCLUSION: Estrogen can
      affect cellular MCCs proliferation and differentiation in a biphasic manner
      depending on the concentration. Estrogen may be vital in the maintenance of
      normal functions of the temporomandibular joint (TMJ) and may be involved in the
      progression of certain TMJ diseases.

PMID- 24437303
TI  - [Establishment of maxillary anterior teeth computer simulation restoration
      system].
AB  - OBJECTIVE: This study aims to simulate restoration of anterior teeth appearance
      by using three-dimensional (3D) reconstruction technique combined with computer
      image processing and 3D animation software. METHODS: The standard teeth model was
      scanned by cone beam CT, and the standard teeth model database was established.
      Using Windows XP, the language system of Microsoft Visual C++6.0 was used. Based
      on MS SQL SERVER2000, the maxillary anterior teeth computer simulation
      restoration system was developed with a 3Ds Max core. The system was used to
      simulate the rehabilitation of maxillary anterior teeth in the clinical setting.
      RESULTS: The maxillary anterior teeth computer simulation restoration system was
      easy to operate, and the simulation results were reliable. CONCLUSION: The
      maxillary anterior teeth computer simulation restoration system can help patients
      understand treatment designs. The system provides an effective means of creating
      patient-desired dental prosthesis with personalized characteristics.

PMID- 24437304
TI  - [Maxillary anterior tooth restoration by using fiber-reinforced composite with a
      natural tooth pontic: a case report].
AB  - Loss of anterior tooth impairs patients physically and emotionally as well as
      presents a challenge for dentists. This article presented a method of replacing
      one anterior tooth that was extracted because of periodontitis. The proposed
      method involves the use of the natural crown as pontic with fiber-reinforced
      composite resin-bonded fixed partial denture.

PMID- 24437305
TI  - [Root canal treatment of two-rooted three-canal maxillary first premolar: a case
      report].
AB  - According to literature, the incidence of three-canal maxillary first premolar is
      between 0.5% and 7.5%. The two types of three-canal maxillary premolars are two
      rooted and three-rooted three-canal maxillary premolars. Most case reports in
      Chinese literature focus on three-rooted three-canal maxillary premolars. To our
      knowledge, no domestic case report on two-rooted three-canal maxillary premolar
      has been published. In this study, we describe the root canal treatment of a two
      rooted three-canal maxillary premolar.

PMID- 24437306
TI  - [Application of adipose-derived mesenchymal stem cells in craniomaxillofacial
      restoration and reconstruction].
AB  - Craniomaxillofacial hard and soft tissue defects are clinically common and
      frequently encountered diseases that seriously affect the appearance and function
      of patients. Restoration and reconstruction of craniomaxillofacial hard and soft
      tissues are comprehensive clinical problems that require a multi-disciplinary
      approach and are faced with many unresolved issues. Development of tissue
      engineering has introduced new concepts to craniomaxillofacial restoration and
      reconstruction. Tissue engineering primarily aims to determine suitable seed
      cells. Recently, adipose-derived mesenchymal stem cells (AdSCs) were found to be
      relatively ideal seed cells because they are easy to obtain from numerous sources
      and have multiple potencies under certain inducing circumstances and high
      augmenting ability. This review provides an overview of the application of AdSCs
      in craniomaxillofacial restoration and reconstruction.

PMID- 24437307
TI  - The effect of zinc and vitamin C supplementation on hemoglobin and hematocrit
      levels and immune response in patients with Plasmodium vivax malaria.
AB  - Plasmodium vivax infection in humans can relapse and is associated with iron
      deficiency. The immune response plays an important role in preventing relapse. In
      this study we analyzed the effect of zinc and vitamin C supplementation on
      hemoglobin and hematocrit levels and immune response in patients with P. vivax
      malaria. We measured immune response by examining interferon gamma (IFN-gamma)
      and interleukin-10 (IL-10) levels. Subjects were divided into either treatment or
      control groups. The treatment group received daily zinc and vitamin C
      supplementation for 45 days. Compliance with supplement consumption was recorded
      weekly. After 45 days of supplementation, IFN-gamma and IL-1 levels were
      remeasured. All study subjects in both groups had normal hemoglobin and
      hematocrit levels. The hemoglobin levels increased only in the supplementation
      group (p=0.011), while hematocrit levels increased in both the supplementation
      (p=0.001) and control (p=0.023) groups. IFN-gamma decreased slightly in the
      supplementation group, but the change was not significant (p=0.688). IL-10
      increased slightly in both the supplementation and the control groups, but the
      change were not significant (p=0.421 and p=0.556, respectively), suggesting the
      elevated hemoglobin and hematocrit levels were unrelated to immune response.

PMID- 24437308
TI  - Schizontemia as an indicator of severe malaria.
AB  - We conducted this study to determine if the finding of schizontemia could be used
      as an indicator of severe falciparum malaria. We enrolled 250 patients with
      severe falciparum malaria and 250 patients with umcomplicated falciparum malaria
      into the study. Severe falciparum malaria was defined following World Health
      Organization criteria (2010). Of the 250 patients with severe falciparum malaria,
      99 (39.6%) had schizontemia on admission. Of the 250 patients with uncomplicated
      falciparum malaria, 0 (0%) had schizontemia (p<0.05). Schizontemia was also found
      to be significantly correlated with parasite density, severe malaria, impaired
      consciousness, pulmonary edema, hypoglycemia, jaundice and hemoglobinuria
      (p<0.05). Schizontemia may be considered as an indicator of severe malaria.

PMID- 24437309
TI  - Knowledge, attitudes and practices among parents and teachers about soil
      transmitted helminthiasis control programs for school children in Guimaras,
      Philippines.
AB  - We determined the attitudes toward and practices regarding soil-transmitted
      helminthes (STH) control among parents and school teachers to identify reasons
      behind attitudes and practices that do not promote STH control. Written
      knowledge, attitudes and practices surveys were distributed to parents (N = 531)
      and teachers (N = 105) of students at 11 elementary schools in Guimaras Province,
      the Philippines. The survey addressed attitudes about mass drug administration
      (MDA), knowledge about STH control, hygienic practices, and acceptability of
      distributing deworming tablets among teachers. More than 90% of parents and
      teachers held favorable attitudes towards MDA. Sixty-nine percent of parents and
      75.5% of teachers believed stool exams were necessary before MDA. Thirty-seven
      percent of parents stated they would not allow teachers to administer deworming
      tablets and 91.5% of parents feared teachers would not detect side effects of the
      medication. Forty-eight percent of teachers felt they could safely give deworming
      tablets and 81.4% of teachers were afraid of managing the side effects of
      deworming tablets. Forty-seven point eight percent of parents and 42.2% of
      teachers stated defecation in the open occured in their community. Although
      attitudes toward STH control were largely favorable, misconceptions about the MDA
      strategy, lack of support for teachers giving deworming tablets, and the practice
      of open defecation still exist as barriers to STH control efforts. The next step
      to achieve effective STH control will be to clarify misconceptions in education
      campaigns, to train teachers about medication administration, campaign to improve
      sanitation and hygiene and begin targeted mass treatment in Guimaras, the
      Philippines.

PMID- 24437310
TI  - Comparative field efficacy of newly developed formulations of larvicides against
      Aedes aegypti (L.) (Diptera: Culicidae).
AB  - Aedes aegypti (L.) is known as vector of dengue and chikungunya fever. Larvicides
      are used to control this vector. We evaluated the efficacy of newly developed
      formulations of larvicides to control Ae. aegypti under field conditions for 24
      weeks post single application. Mosdop P and Mosdop TB containing diflubenzuron
      (2% and 40 mg/tablet, respectively) as the active ingredient, were applied at a
      dosage of 0.1 mg a.i./1 and Mosquit TB10, Mosquit TB100 and Temecal containing
      temephos (1%, 10% and 1%, respectively) as the active ingredient were applied at
      a dosage of 1 mg active ingredent (a.i.) to 200 liter water storage jars. Two
      water regimens were used in the jars: in one regimen the jar was kept full of
      water all the time and in the other regimen a full jar had half the volume
      removed and refilled weekly. The larvicidal efficacy was reported as the level of
      inhibition of emergence (IE%) calculated based on the pupal skins in the jars
      versus the original number of larvae added. Mosdop P, Mosdop TB, Mosquit TB10,
      Mosquit TB100 and Temecal showed complete larvicidal efficacy (100% IE) in the
      constantly full jars for 16, 17, 14, 20 and 13 weeks posttreatment, respectively;
      in the jars where half the volum of water was replaced weekly, the larvicides had
      complete larvicidal efficacy (100% IE) for 19, 20, 17, 24 and 15 weeks post
      treatment, respectively. The five larvicide regimens evaluated in this study are
      effective for controlling Ae. aegypti larvae.

PMID- 24437311
TI  - Larvicidal and pupicidal activities of essential oils from Zingiberaceae plants
      against Aedes aegypti (Linn.) and Culex quinquefasciatus say mosquitoes.
AB  - We conducted this study to investigate the efficacy of herbal essential oils from
      12 species of Zingiberaceae plants to determine their larvicidal and pupicidal
      activity against fourth instar larvae and pupae of Aedes aegypti and Culex
      quinquefasciatus mosquitoes. Probit analysis was used to analyze the data. Larval
      mortality was recorded at 1, 5, 10, 15, 30 and 60 minutes and 24 hours. Pupal
      mortality was recorded at 15 and 30 minutes and 1, 3, 6, 12, 24 and 48 hours. All
      the essential oils tested showed larvicidal activity. Zingiber cassumunar and
      Amomum biflorum oils proved to have the greatest activity against Ae. aegypti
      larvae with LT50 of 1.4 minutes and 100% mortality at 5 and 10 minutes,
      respectively. Boesenbergia rotunda, Curcuma zedoaria and Hedychium coronarium
      essential oils had activity against Cx. quinquefasciatus larvae with LT50 of 1.7
      minutes and 100% mortality at 10 minutes, 5 minutes and 15 minutes, respectively.
      All the herbal essential oils tested resulted in 100% mortality against Ae.
      aegypti and Cx. quinquefasciatus larvae at 60 minutes and 30 minutes,
      respectively. Ae. aegypti and Cx. quinquefasciatus pupae were susceptible to Z.
      ottensii oil (LT50 of 0.2 hour) and Z. zerumbet oil (LT50 of 0.6 hour) and had
      pupicidal activity with 100% mortality at 6 and 3 hours, respectively. All the
      essential oils test had pupicidal activity against Ae. aegypti and Cx.
      quinquefasciatus by inducing 100% mortality at 48 hours.

PMID- 24437312
TI  - Differences in clinical features between children and adults with dengue
      hemorrhagic fever/dengue shock syndrome.
AB  - This retrospective study was conducted to assess the differences in clinical
      features between children and adults with dengue hemorrhagic fever/ dengue shock
      syndrome (DHF/DSS) admitted to Ratchaburi Hospital, Ratchaburi Province,
      Thailand. A total of 273 patients with DHF/DSS admitted to Ratchaburi Hospital
      during January 2007 to May 2008 were included in the study. The median age
      (range) of studied subjects was 16 years (6 months to 62 years) and the ratio of
      adults to children was 1.6:1. Forty-eight percent of subjects were 16-30 years
      old. The common signs, symptoms and clinical features were: nausea/vomiting
      (74.0%), a positive tourniquet test (73.0%), anorexia (67.0%), hemoconcentration
      (58.0%), headache (54.0%), abdominal tenderness (43.0%), myalgia (39.0%) and
      pleural effusion (20.0%). Children had anorexia, a positive tourniquet test,
      abdominal tenderness and a convalescent rash more frequently than adults.
      Children also had significantly more prominent plasma leakage as shown by lower
      serum albumin and sodium and a higher prevalence of pleural effusion, ascites and
      shock. Although not statistically significant, the prevalence of bleeding in
      children was higher than in adults but more adults needed blood transfusion. This
      study provides additional insight into the clinical picture of DHF/DSS in adults
      and children and may be beneficial for clinicians caring for these adults and
      children.

PMID- 24437313
TI  - Prevalence and characteristics of dengue and chikungunya infections among acute
      febrile patients in Nong Khai Province, Thailand.
AB  - We conducted a cross sectional study at three hospitals of Nong Khai Province,
      Thailand to determine the prevalence and characteristics of dengue and
      chikungunya infection among patients who sought care. The study population was
      acute febrile patients who visited these hospitals during 1 August -31 October,
      2010 who were aged 2-60 years and had clinical symptoms compatible with the case
      definition. Dengue and chikungunya cases were confirmed by an ELISA IgM titer or
      RT-PCR. We also reviewed surveillance data of dengue and chikungunya infections
      from 2003-2009. Of the 200 participants recruited into the study, 103 patients
      (51.5%) were confirmed to have acute dengue infection; dengue serotype 2 was the
      most prevalence serotype. The ages of confirmed dengue cases ranged from 2-37
      years old. The distribution of cases showed that dengue morbidity tended to be
      clustered in adjacent areas, particularly in Mueang District. Only a small
      proportion of the patients uses mosquito repellant and had screens on their
      windows. One patient (0.5%) had laboratory confirmed chikungunya infection. She
      was from Rattanawapi District, an area where no chikungunya had been reported
      before. Since the disease varies by age and geographic location, increased
      awareness of health care workers and public health officers about the diseases in
      the area is needed for early detection of cases and to promote early prevention
      and control measures.

PMID- 24437314
TI  - Hospital-based surveillance of Japanese encephalitis at a tertiary hospital in
      Manila.
AB  - Japanese encephalitis virus (JEV) is endemic in the Philippines but the incidence
      and burden of disease are not well established. We conducted a prospective
      hospital-based study at San Lazaro Hospital, a tertiary level hospital in Manila,
      from September 2005 to December 2006. Cases were determined using an in-house
      dengue and Japanese encephalitis (JE) enzyme-linked immunosorbent assay in order
      to detect the proportion of JE cases among the acute encephalitis syndrome (AES)
      cases admitted to our hospital. Fifteen patients were found to have AES, of whom
      6 (40%) had confirmed JE. Of the JE cases, 4 were females and 2 were males with
      an age range of 3-14 years. Three of the 6 JE cases occurred during July. The
      most common signs and symptoms on admission among JE cases were: fever, headache,
      loss of appetite, neck rigidity and altered sensorium. JE likely comprises a
      significant proportion of hospitalized AES cases among children from Manila and
      nearby provinces. Further studies on the nation-wide prevalence and distribution
      of JE in the Philippines are needed to guide health authorities in disease
      control and prevention strategies.

PMID- 24437315
TI  - Susceptibility of openbill storks (Anastomius oscitans) to highly pathogenic
      avian influenza virus subtype H5N1.
AB  - This investigation detailed the clinical disease, gross and histologic lesions in
      juvenile openbill storks (Anastomus oscitans) intranasally inoculated with an
      avian influenza virus, A/chicken/Thailand/vsmu-3 (H5N1), which is highly
      pathogenic for chickens. High morbidity and mortality were observed in openbill
      storks inoculated with HPAI H5N1 virus. Gross lesions from infected birds were
      congestion and brain hemorrhage (10/20), pericardial effusions, pericarditis and
      focal necrosis of the cardiac muscle (2/20), pulmonary edema and pulmonary
      necrosis, serosanguineous fluid in the bronchis (16/20), liver congestion (6/20),
      bursitis (5/20), subcutaneous hemorrhages (2/20) and pinpoint proventiculus
      hemorrhage (2/20). Real time RT-PCR demonstrated the presence of viral RNA in
      organs associated with the lesions: brain, trachea, lungs, liver, spleen and
      intestines. Similar to viral genome detection, virus was also isolated from these
      vital organs. Antibodies to influenza virus detected with a hemagglutination
      inhibition test, were found only in the openbill storks who died 8 days post
      inoculation.

PMID- 24437316
TI  - Prevalence and risk factors for HIV infection among men having sex with men in
      Metro Manila, Philippines.
AB  - HIV incidence in the Philippines is increasing at an alarming rate. We conducted
      this study to understand the factors catalyzing the HIV epidemic among men having
      sex with men (MSM) in Metro Manila. From November 2009 to January 2010, an HIV
      testing booth was set up adjacent to bars and restaurants in Metro Manila
      frequented by MSM at night. Participants aged > or =18 years were interviewed
      using a structured questionnaire. Rapid HIV antibody screening was performed
      using SD Bioline HIV 1/2 3.0 (Standard Diagnostics). Of 406 MSM included in the
      study, the mean age was 26.2 years [standard deviation (SD) 5.4]; 96% believed
      condoms reduced HIV risk but only 3% reported consistent use. The leading reasons
      for not using condoms were belief that the partner was HIV negative (34.4%),
      diminished pleasure (32%), and unavailability (23.4%). The HIV prevalence using
      the rapid test was 11.8% [95% confidence interval (CI): 8.7- 15.0]. All 40 cases
      who had a confirmatory Western blot test were positive, of whom 24 were business
      process outsourcing employees (BPOEs). On multivariate analysis, work as a BPOE
      [adjusted OR (aOR): 3.37; p=0.001], preference for receptive anal sex (aOR: 5.26;
      p=0.04), and sex while under the influence of excessive alcohol (aOR: 2.71;
      p=0.04) were independently associated with HIV. The proportion of BPOEs who
      consistently use condoms when having insertive anal sex with a stranger was
      significantly lower compared to non-BPOEs (24.5% versus 38.2%; p=0.02). Urgent
      interventions are needed to address the HIV epidemic in the Philippines.

PMID- 24437317
TI  - Risk of cardiovascular events predicted by the Rama-EGAT score among HIV-infected
      patients in Thailand.
AB  - Cardiovascular disease has become an important cause of death among HIV-infected
      patients. A cross sectional study was conducted to determine the risk for
      cardiovascular events among HIV-infected patients who visited the Infectious
      Disease Clinic at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
      The risk for cardiovascular events was determined using the Rama-EGAT risk score.
      Patients were categorized into two groups by score: high risk group with a Rama
      EGAT score > or =6 and low risk group with a Rama-EGAT score <6. One hundred nine
      patients were included in the study. The mean age of participants was 47.3 years
      old, 73 (67%) were male. Mean duration of HIV infection among participants was
      8.5 years and the mean CD4 cell count was 485 cells/mm(3). Nearly all the
      patients had received antiretroviral therapy. The mean body weight and body mass
      index (BMI) were 61.2 kg and 22.5 kg/m(2), respectively. Of the 109 participants,
      12 (11%) had a high risk for cardiovascular events. On multivariate analysis,
      older age [odds ratio (OR) per 5 years increase = 8.6; p=0.005], diabetes
      mellitus (OR = 63.1; p=0.020) and lower HDL (OR per 5 mg/dl decrease = 4.3,
      p=0.020) were factors significantly associated with high EGAT risk score. Early
      screening for diabetes mellitus and HDL levels, as well as appropriate glycemic
      control and regular exercise are crucial for preventing cardiovascular events
      among HIV-infected patients receiving antiretroviral therapy in Thailand.

PMID- 24437318
TI  - Variables influencing anti-human immunodeficiency virus type 1 neutralizing human
      monoclonal antibody (NhMAb) production among infected Thais.
AB  - We conducted this study to determine the clinical variables associated with the
      production of human immunodeficiency virus type 1 (HIV-1) circulating recombinant
      form (CRF) 01_AE neutralizing human monoclonal antibodies (NhMAbs) using a
      hybridoma technique. This cross sectional study was performed in 20 asymptomatic
      HIV-1-infected Thais. Peripheral blood mononuclear cells (PBMCs) were obtained
      from each study participant and fused with SPYMEG cells. Culture supernatant
      collected from growing hybridomas was tested for neutralizing activity against
      HIV-1 CRF01_AE Env-recombinant viruses. Fifty hybridomas expressing anti-HIV-1
      NhMAbs with strong neutralizing activity against at least 1 CRF01_AE Env
      recombinant virus were found. A positive association between the numbers of
      hybridomas produced and the CD4 counts of study participants (p = 0.019) was
      observed. NhMAb-producing hybridomas with strong neutralizing activity were
      mostly found in participans diagnosed with HIV-1 infection within the previous 1
      year. The HIV-1 viral load was not significantly correlated with the numbers of
      either established hybridomas or clones expressing anti-HIV-1 NhMAbs with strong
      neutralizing activity. To our knowledge, this is the first study of NhMAb
      producing hybridomas obtained from HIV-1 CRF01_AE-infected populations identified
      by antibody binding to HIV-1 V3 loop peptide enzyme-linked immunosorbent assay
      (ELISA) or TRUGENE HIV-1 Genotyping Assay (HIV-1 pol sequence). It provides
      important criterion to slect study participants with high CD4 counts who produce
      large numbers of hybridoma clones. The results are valuable for further studies
      related to nurtalizing antibodies production and HIV-1 vaccine development.

PMID- 24437319
TI  - Gender and ethnic disparities of HIV and syphilis seroconversions in a 4-year
      cohort of injection drug users.
AB  - This study assessed gender and ethnic disparities of HIV and syphilis
      seroconversions in a cohort of injection drug users (IDUs) in Southwest China. A
      cohort of HIV-seronegative IDUs was followed up from November 2002 to January
      2007. The average seroincidence for HIV and syphilis was 2.2 and 4.2 per 100
      person-years (PYs), respectively. Multivariable Poisson regression models
      indicated that the predictors for incident HIV seroconversion included non-Han
      minority ethnic groups (RR: 5.2; 95% CI: 1.9-14.4) and injecting drugs > or = 7
      times/week in the past 3 months (RR: 3.6; 95% CI: 1.4-9.8). The predictors for
      incident syphilis seroconversion included female (RR: 4.1; 95% CI: 1.8-9.3) and
      being married or cohabiting (RR: 2.7; 95% CI: 1.2-5.9). These findings suggested
      that HIV continues to spread among IDUs, especially among Yi and other minority
      ethnic groups, and frequent risky injections might be the major diver of the
      epidemic. Female IDUs are disproportionally affected by syphilis. Further
      research is needed to better understand the ethnicity disparity for HIV and
      gender disparity for syphilis.

PMID- 24437320
TI  - Role of combined zinc, vitamin A, and fish oil supplementation in childhood
      tuberculosis.
AB  - This objective of this study was to determine benefit of one month combined
      supplementation (zinc, vitamin A, fish oil) along with anti-tuberculosis drugs
      (ATD) on increasing serum leptin levels and decreasing tumor necrosis factor
      alpha (TNF-alpha) in children with tuberculosis (TB). A quasi experimental study
      was conducted on 22 children (aged 5-14 years) with a positive acid-fast bacilli
      (AFB) smear. The children were divided into 2 groups. A history, physical
      examination, anthropometric measurements, serum leptin levels, TNF-alpha levels,
      retinol and zinc levels were examined in all subjects before and after treatment.
      Nutritional supplementation and ATD were given to group I while ATD only were
      given to group II. The change in leptin, TNF-alpha, retinol and zinc levels were
      analyzed with the Mann-Whitney test, while a t-test was used to determine changes
      in body mass index (BMI). Group I had a higher significant increase in serum
      leptin levels than group II (p=0.034). Group I had a significantly greater
      decrease in TNF-a levels than group II (p=0.032). No significant differences in
      retinol or zinc levels were seen between the two, but both groups had an increase
      after treatment. Both groups had a significant increase in BMI (p=<0.001) post
      treatment compared to pre-treatment. Supplementation with zinc, vitamin A and
      fish oil is associated with a significant increase in leptin levels and a
      significant decrease in TNF-alpha levels among children treated for TB. No
      significant benefit was seen in BMI among children receiving supplementation
      compared to those without it, although ATD resulted in a significant increase in
      BMI in both groups.

PMID- 24437321
TI  - Uncommon clinical presentations of melioidosis in children: 2 cases with sore
      throat and 1 case with urticarial rash.
AB  - Common clinical presentations of melioidosis in children include suppurative
      parotitis, lymphadenitis, skin infection and septicemia with pneumonia. Here we
      describe three cases with uncommon presentations of melioidosis seen among
      children attending a university hospital in northeastern Thailand. Two patients
      presented with pharyngitis and subsequently developed cervical lymphadenitis.
      Another patient presented with high fever and generalized urticarial rash. A
      pharyngeal culture in each of the first 2 patients and a blood culture and
      culture of the discharge from the wound of the third patient grew Burkholderia
      pseudomallei. All patients recovered with treatment. Their clinical
      presentations, initial diagnosis, treatment, clinical course and outcomes are
      described. Physicians caring for children living in, or returning from,
      melioidosis endemic areas should be aware of these uncommon presentations.

PMID- 24437322
TI  - Duplex PCR for detection of Salmonella and Shigella spp in cockle samples.
AB  - Salmonella and Shigella spp are important causative agents of foodborne diseases.
      A sensitive, specific and rapid method is essential for detection of these
      pathogens. In this study, a duplex PCR method was developed for simultaneous
      detection of Salmonella and Shigella spp in cockle samples and compared with the
      traditional culture method. Enrichment broths for Salmonella spp recovery were
      also compared. Sensitivity of the duplex PCR for simultaneous detection of
      Salmonella and Shigella spp from pure culture was 10(3) CFU/ml (40 CFU/PCR
      reaction), and that of sterile cockle samples spiked with these two pathogens was
      1 CFU/10 g of cockle tissue after 9 hours enrichment [3 hours in buffered peptone
      water (BPW), followed by 6 hours in Rappaport Vasiliadis (RV) broth or
      tetrathionate (TT) broth for Salmonella spp and 6 hours enrichment in Shigella
      broth (SB) for Shigella spp]. There was no significant difference in detection
      sensitivity between enrichment in RV and TT broths. Salmonella spp detected in
      cockles in Khon Kaen, Thailand by duplex PCR and culture method was 17% and 13%,
      respectively but Shigella spp was not detected. The duplex PCR technique
      developed for simultaneous detection of Salmonella and Shigella spp in cockle
      samples was highly sensitive, specific and rapid and could serve as a suitable
      method for food safety assessment.

PMID- 24437323
TI  - Macrolide resistant Streptococcus pneumoniae in Charoenkrung Pracharak Hospital,
      Thailand.
AB  - Macrolide resistant Streptococcus pneumoniae has been increasing rapidly in
      Southeast Asia. A review from 2000 through 2011 at Charoenkrung Pracharak
      Hospital that evaluated drug resistance to erythromycin found S. pneumoniae from
      158 of the 390 (40.5%) patients: 3.6% intermediate, 36.9% highly resistant. A
      significant correlation was found between macrolide resistant S. pneumoniae and
      penicillin resistance (p<0.001), macrolide susceptible pneumococci and penicillin
      susceptibility (p<0.001). Trends of macrolide resistant S. pneumoniae at
      Charoenkrung Pracharak Hospital were found to have increased. Therefore,
      macrolide monotherapy should be avoided or care should be taken for prophylaxis
      or treatment in the patient suspected of S. pneumoniae infection.

PMID- 24437325
TI  - Peak expiratory flow rates among women exposed to different cooking fuels in
      rural India.
AB  - Plant or animal based material burned for cooking or heating (biofuels) can cause
      indoor air pollution. We studied the effect of exposure to biofuel and other
      types of fuel smoke on peak expiratory flow rates (PEFR) among rural Indian
      women. We conducted a community based cross-sectional study of 760 non-smoking
      women who cooked using one of four types of fuel: biofuel, kerosene, liquefied
      petroleum gas (LPG) or a combination of two or more fuels. A PEFR <80% of
      predicted was considered abnormal. An abnormal PEFR was seen in 43.3% of women
      using biofuels, 20.5% of those using kerosene, 23.4% of those using LPG and 21.4%
      of those using mixed fuel. Multivariate logistic regression analysis showed among
      those using mixed fuel, age [OR: - 2.08, 95% confidence interval (CI): 1.32 -
      3.28, p = 0.00], height (OR: -1.06, 95% CI: 1.00 - 1.12, p = 0.02) and exposure
      index (estimated hours spent cooking daily multiplied by the years cooked) (OR: 
      2.74, 95% CI: 1.68 - 4.47, p = 0.00) were significant predictors of abnormal
      PEFR. Among women using biofuels and LPG, only exposure index was found to be a
      significant predictor of abnormal PEFR (p<0.05). No significant association was
      found between abnormal PEFR and exposure index among women who used only kerosene
      for fuel (p>0.05). Using mixed fuel was found to be more likely to cause an
      abnormal PEFR.

PMID- 24437324
TI  - Use of and attitudes toward tobacco and alcohol among adults in southern Sri
      Lanka.
AB  - The adverse health effects of tobacco and alcohol are well known. Alcohol
      consumption is increasing in Sri Lanka, but few population studies have been
      conducted. The objective of this study was to document tobacco and alcohol
      consumption levels among adults in southern Sri Lanka and to identify the main
      reasons for using or refraining from alcohol and tobacco products. Tobacco and
      alcohol use within Sri Lanka is relatively common, particularly among adult
      males. Reasons given for smoking and drinking frequently relate to social and
      image-based motivators. Women may be especially susceptible to the influence of
      peer pressure in social situations. Public health efforts should consider the use
      of demographic-specific anti-tobacco and anti-alcohol messages, as the motivators
      driving behavior appear to differ across gender and age groups.

PMID- 24437326
TI  - Factors related to falls among community dwelling elderly.
AB  - Falls among the elderly can lead to disability, hospitalization and premature
      death. This study aimed to determine the factors related to falls among community
      dwelling elderly. This case-control study was conducted at the Samlium Primary
      Care Unit (SPCU), Khon Kaen, Thailand. Cases were elderly individuals who had
      fallen within the previous six months and controls were elderly who had not
      fallen during that same time period. Subjects were taken from elderly persons
      registered at the SPCU. The sample size was calculated to be 111 cases and 222
      controls. Face to face interviews were conducted with subjects between May and
      June, 2011. The response rate was 100%. On bivariate analysis, the statistically
      significant factors related to falls were: regular medication use, co
      morbidities, mobility, depression, cluttered rooms, slippery floors, unsupported
      toilets (without a hand rail), sufficient exercise, rapid posture change and
      wearing slippers. When controlling for others significant factors, multiple
      logistic regression revealed significant factors were: regular medication use
      (AOR: 2.22; 95%CI: 1.19 - 4.12), depression (AOR: 1.76, 95% CI: 1.03 - 2.99),
      sufficient exercise (AOR: 0.34; 95% CI: 0.19 - 0.58) and wearing slippery shoes
      (AOR: 2.31; 95% CI: 1.24 - 4.29). Interventions need to be considered to modify
      these significant factors associated with falls and education should be provided
      to these at risk.

PMID- 24437327
TI  - Validation of the parenting sense of competence scale in fathers: Thai version.
AB  - The role of the parent is a significant family factor that can impact the child
      cognitively, emotionally, and socially. Strengthening parents' competence
      improves their performance as parents. This study is the development and
      validation of the Thai Parenting Sense of Competence scale (Thai PSOC scale) for
      assessing the parenting competence of Thai fathers. The Thai PSOC scale was
      revised from the PSOC scale developed by Gibaud-Wallston and Wandersman (1978).
      The scale consists of 17 items with 2 subscales: skill/knowledge (8 items) and
      valuing/comfort (9 items). The scale was tested with 195 Thai fathers-to-be/
      fathers. The results showed high internal consistency: 0.78 for the total scale
      and 0.73 and 0.80 for the skill/knowledge and valuing/comfort subscales,
      respectively. Confirmatory factor analysis (CFA) led to a revision of the Thai
      PSOC scale with better goodness of fit indices for the sample. In the revised
      scale with Item 17 was omitted, several goodness of fit indices improved
      significantly with a more acceptable, good fit (Chi(2)/df = 1.63; RMSEA = 0.06;
      GFI = 0.91; AGFI = 0.88; NFI = 0.80; TLI = 0.90; CFI = 0.91). With revision, the
      Thai PSOC scale is a potential instrument to measure parenting competence in Thai
      fathers.

PMID- 24437328
TI  - Effect of soft drinks on the release of calcium from enamel surfaces.
AB  - Continuous consumption of soft drinks is the main cause of potential oral health
      problems, including dental caries and erosion. The purpose of this study was to
      compare the effect of three different types of soft drinks on the release of
      calcium from the enamel surface of teeth. Forty bovine teeth were selected for
      the experiment. They were divided into four groups (n=10/group): Group 1 (Coke),
      Group 2 (Pepsi), Group 3 (Sprite), and Group 4 (distilled water, the control).
      The pH of each beverage was measured using a pH meter. The release of calcium
      ions was measured using an atomic absorption spectrophotometer at baseline, 15,
      30, and 60 minutes. The results were assessed by analysis of variance and then by
      the Tukey test (p< 0.05). Coke, with a pH of 2.39, was the most acidic among the
      soft drinks. Coke, Pepsi, and Sprite showed no significant mean differences in
      the calcium released, but there was a significant mean difference of these soft
      drinks with distilled water at 60 minutes. We concluded that prolonged exposure
      to soft drinks could lead to significant enamel loss.

PMID- 24437330
TI  - Late abortion in case of severe foetal abnormality.

PMID- 24437329
TI  - Microleakage of two fluoride-releasing sealants when applied following saliva
      contamination.
AB  - The purpose of this in vitro study was to evaluate microleakage of two fluoride
      releasing sealants in saliva contaminated and non-contaminated conditions. Twenty
      four human third molars were randomly assigned to two groups: saliva contaminated
      and saliva non-contaminated teeth. In the contaminated group, the teeth were
      contaminated with 0.02 ml artificial saliva for 20 seconds and blowed dry
      afterward. Each group was divided into two subgroups: Group A, a fluoride
      releasing resin sealant marketed as Clinpro and Group B, a glass-ionomer sealant
      marketed as Fuji VII. After sealant application, all the teeth were thermocycled
      for 2,000 cycles and coated with nail varnish 1.0 mm from the sealed areas. The
      teeth were stained with 2% methylene blue dye for 24 hours and sectioned in the
      bucco-lingual direction. Dye penetration (microleakage) was examined with a 25x
      polarized light microscope and measured by a computerized-calculated method. Data
      were compared with the Mann-Whitney U test at significance level of p<0.05. A
      comparison of the two types of sealant revealed microleakage of the glass-ionomer
      sealant was present but there was no significant difference between the saliva
      contaminated and saliva non-contaminated teeth. Microleakage of the fluoride
      releasing resin sealant was present and was greater among the saliva-contaminated
      teeth than the saliva non-contaminated teeth. The glass-ionomer sealant had
      significantly greater microleakage than the fluoride-relasing resin-based sealant
      in both the saliva-contaminated and saliva non-contaminated teeth.

PMID- 24437331
TI  - The Dutch Euthanasia Act: recent legal developments.
AB  - The Dutch Termination of Life on Request and Assisted Suicide Act [Wet toetsing
      levensbeeindiging op verzoek en hulp bij zelfdoding (Wtl)] came into force in
      2002. Its aim is to increase the degree of due care exercised by physicians when
      terminating a patient's life and to provide a legal framework within which
      physicians account for their actions in such cases. On the basis of the second
      evaluation of the Act, published in December 2012, this article provides an
      overview of the most recent legal developments regarding the Dutch Euthanasia
      Act. Special attention is given to patients with dementia, psychiatric patients
      and patient who are "weary of life".

PMID- 24437332
TI  - Assessing legal advocacy to advance Roma health in Macedonia, Romania, and
      Serbia.
AB  - Across Europe, Roma suffer extreme marginalisation, negatively impacting their
      health. Many cannot access healthcare at all. For others, the health system is a
      hostile place. At the same time, good legal frameworks are in place to protect
      health rights, and there is increasing recognition of systemic violations
      experienced by Roma. Essential to building on this momentum and closing the gap
      between standards and implementation is Roma ability to conduct legal advocacy
      Since 2010, the Open Society Foundations has supported Roma engagement in
      Macedonia, Romania and Serbia in the following advocacy strategies: i) legal
      empowerment, ii) documentation and advocacy, iii) media advocacy, and iv)
      strategic litigation. This article presents a framework developed to evaluate the
      effectiveness of these efforts and a baseline against which outcomes can be
      measured in a few years. The evaluation framework provides a qualitative
      assessment of Roma capacity, accountability for violations, changes in law and
      practice, and impact on communities. Findings reveal that that presently Roma
      lack knowledge of their rights and rarely challenge violations. Accountability in
      healthcare is practically non-existent. However, where legal advocacy has been
      used, violations decrease, and power dynamics shift. As healthcare becomes more
      responsive to communities, it also better serves non-Roma citizens.

PMID- 24437333
TI  - European Court of Human Rights. ECHR 2013/19. Case of Avilkina and others v.
      Russia, 6 June 2013, no. 1585/09 (first section).

PMID- 24437334
TI  - European Court of Human Rights. ECHR 2013/20. Case of Nencheva and others v.
      Bulgaria, 18 June 2013, no. 48609/06 (former fourth section).

PMID- 24437335
TI  - European Court of Human Rights. ECHR 2013/21. Case of Dmitriy Ryabov v. Russia, 1
      August 2013, no. 33774/08 (first section).

PMID- 24437336
TI  - ECJ 2013/XX, Federation des maisons de repos privees de Belgique (Femarbel) ASBL
      v. Commission communautaire commune de Bruxelles-Capitale, 11 July 2013 (C
      57/12).

PMID- 24437337
TI  - Anonymity and openness in donor conception: the new Danish model.

PMID- 24437338
TI  - Examining the relationship between communities' 'age-friendliness' and life
      satisfaction and self-perceived health in rural Manitoba, Canada.
AB  - INTRODUCTION: Population aging is a worldwide phenomenon. As a response, the
      World Health Organization (WHO) introduced the concept of 'age-friendliness' in
      2006. Age-friendliness is defined in terms of a range of domains, such as
      housing, opportunities for participation, and transportation. Communities that
      accommodate the needs of older adults in these domains will, it is thought,
      promote healthy, active aging. The purpose of the present study was to examine
      communities' age-friendliness and its relationship to health-related outcomes in
      a rural context. METHODS: The study included 29 communities located in Manitoba,
      a mid-Western Canadian province, that are part of the Province of Manitoba's Age
      Friendly Manitoba Initiative. As part of a needs assessment process in these
      communities, 593 individuals, including seniors and younger adults, completed an
      Age-Friendly Survey. The survey was designed to measure a variety of features in
      seven domains (the physical environment, housing options, the social environment,
      opportunities for participation, community supports and healthcare services,
      transportation options, and communication and information), as well as containing
      measures of life satisfaction and self-perceived health. Community
      characteristics were derived from census data. Moreover, communities were
      categorized on a rural-urban continuum. RESULTS: Multi-level regressions
      indicated that an overall Age-Friendly Index was positively related to both life
      satisfaction (b=0.019, p<0.0001) and self-perceived health (b=0.013, p<0.01).
      When examining more specifically each of the seven age-friendly domains, all but
      housing was positively related to life satisfaction. Results were not as
      consistent for self-perceived health, with significant relationships emerging
      only for the physical environment, social environment, opportunities for
      participation, and transportation options. A subsequent analysis for seniors
      versus younger participants, respectively, indicated that significant
      relationships between age-friendly domains and life satisfaction and self
      perceived health were restricted primarily to seniors. None of the community
      characteristics were related to life satisfaction and self-perceived health, nor
      was degree of rurality. CONCLUSIONS: The concept of age-friendliness has been
      garnering considerable attention from policy-makers as a way to promote healthy
      aging. For example, in Canada, several provinces have launched age-friendly
      initiatives. Although causality cannot be inferred from the present, cross
      sectional study, the findings are encouraging as they show that age-friendliness
      is associated with enhanced life satisfaction and self-perceived health in a
      rural context. The study further supports the notion that a wide range of domains
      within the community environment are important in older adults' lives and need to
      be considered. Public policy initiatives, such as the Province of Manitoba's Age
      Friendly Initiative, may thus be one approach to enhancing healthy aging in rural
      settings.

PMID- 24437339
TI  - Quantifying contribution of synthrophic acetate oxidation to methane production
      in thermophilic anaerobic reactors by membrane inlet mass spectrometry.
AB  - A unique method was developed and applied for monitoring methanogenesis pathways
      based on isotope labeled substrates combined with online membrane inlet
      quadrupole mass spectrometry (MIMS). In our study, a fermentation sample from a
      full-scale biogas plant fed with pig and cattle manure, maize silage, and deep
      litter was incubated with 100 mM of [2-(13)C] sodium acetate under thermophilic
      anaerobic conditions. MIMS was used to measure the isotopic distribution of
      dissolved CO2 and CH4 during the degradation of acetate, while excluding
      interference from water by applying a cold trap. After 6 days of incubation, the
      proportion of methane derived from reduction of CO2 had increased significantly
      and reached up to 87% of total methane, suggesting that synthrophic acetate
      oxidation coupled to hydrogenotrophic methanogenesis (SAO-HM) played an important
      role in the degradation of acetate. This study provided a new approach for online
      quantification of the relative contribution of methanogenesis pathways to methane
      production with a time resolution shorter than one minute. The observed
      contribution of SAO-HM to methane production under the tested conditions
      challenges the current widely accepted anaerobic digestion model (ADM1), which
      strongly emphasizes the importance of the acetoclastic methanogenesis. 

PMID- 24437340
TI  - Back electron-hole recombination in hematite photoanodes for water splitting.
AB  - The kinetic competition between electron-hole recombination and water oxidation
      is a key consideration for the development of efficient photoanodes for solar
      driven water splitting. In this study, we employed three complementary
      techniques, transient absorption spectroscopy (TAS), transient photocurrent
      spectroscopy (TPC), and electrochemical impedance spectroscopy (EIS), to address
      this issue for one of the most widely studied photoanode systems: nanostructured
      hematite thin films. For the first time, we show a quantitative agreement between
      all three techniques. In particular, all three methods show the presence of a
      recombination process on the 10 ms to 1 s time scale, with the time scale and
      yield of this loss process being dependent upon applied bias. From comparison of
      data between these techniques, we are able to assign this recombination phase to
      recombination of bulk hematite electrons with long-lived holes accumulated at the
      semiconductor/electrolyte interface. The data from all three techniques are shown
      to be consistent with a simple kinetic model based on competition between this,
      bias dependent, recombination pathway and water oxidation by these long-lived
      holes. Contrary to most existing models, this simple model does not require the
      consideration of surface states located energetically inside the band gap. These
      data suggest two distinct roles for the space charge layer developed at the
      semiconductor/electrolyte interface under anodic bias. Under modest anodic bias
      (just anodic of flatband), this space charge layer enables the spatial separation
      of initially generated electrons and holes following photon absorption,
      generating relatively long-lived holes (milliseconds) at the semiconductor
      surface. However, under such modest bias conditions, the energetic barrier
      generated by the space charge layer field is insufficient to prevent the
      subsequent recombination of these holes with electrons in the semiconductor bulk
      on a time scale faster than water oxidation. Preventing this back electron-hole
      recombination requires the application of stronger anodic bias, and is a key
      reason why the onset potential for photocurrent generation in hematite
      photoanodes is typically ~500 mV anodic of flat band and therefore needs to be
      accounted for in electrode design for PEC water splitting.

PMID- 24437341
TI  - One-Pot synthesized bicontinuous hierarchical Li3V2(PO4)3/C mesoporous nanowires
      for high-rate and ultralong-life lithium-ion batteries.
AB  - Lithium-ion batteries have attracted enormous attention for large-scale and
      sustainable energy storage applications. Here we present a design of hierarchical
      Li3V2(PO4)3/C mesoporous nanowires via one-pot synthesis process. The mesoporous
      structure is directly in situ carbonized from the surfactants (CTAB and oxalic
      acid) along with the crystallization of Li3V2(PO4)3 without using any hard
      templates. As a cathode for lithium-ion battery, the Li3V2(PO4)3/C mesoporous
      nanowires exhibit outstanding high-rate and ultralong-life performance with
      capacity retention of 80.0% after 3000 cycles at 5 C in 3-4.3 V. Even at 10 C, it
      still delivers 88.0% of its theoretical capacity. The ability to provide this
      level of performance is attributed to the hierarchical mesoporous nanowires with
      bicontinuous electron/ion pathways, large electrode-electrolyte contact area, low
      charge transfer resistance, and robust structure stability upon prolonged
      cycling. Our work demonstrates that the unique mesoporous nanowires structure is
      favorable for improving the cyclability and rate capability in energy storage
      applications. 

PMID- 24437342
TI  - Production of site-specific antibody-drug conjugates using optimized non-natural
      amino acids in a cell-free expression system.
AB  - Antibody-drug conjugates (ADCs) are a targeted chemotherapeutic currently at the
      cutting edge of oncology medicine. These hybrid molecules consist of a tumor
      antigen-specific antibody coupled to a chemotherapeutic small molecule. Through
      targeted delivery of potent cytotoxins, ADCs exhibit improved therapeutic index
      and enhanced efficacy relative to traditional chemotherapies and monoclonal
      antibody therapies. The currently FDA-approved ADCs, Kadcyla (Immunogen/Roche)
      and Adcetris (Seattle Genetics), are produced by conjugation to surface-exposed
      lysines, or partial disulfide reduction and conjugation to free cysteines,
      respectively. These stochastic modes of conjugation lead to heterogeneous drug
      products with varied numbers of drugs conjugated across several possible sites.
      As a consequence, the field has limited understanding of the relationships
      between the site and extent of drug loading and ADC attributes such as efficacy,
      safety, pharmacokinetics, and immunogenicity. A robust platform for rapid
      production of ADCs with defined and uniform sites of drug conjugation would
      enable such studies. We have established a cell-free protein expression system
      for production of antibody drug conjugates through site-specific incorporation of
      the optimized non-natural amino acid, para-azidomethyl-l-phenylalanine (pAMF). By
      using our cell-free protein synthesis platform to directly screen a library of
      aaRS variants, we have discovered a novel variant of the Methanococcus jannaschii
      tyrosyl tRNA synthetase (TyrRS), with a high activity and specificity toward
      pAMF. We demonstrate that site-specific incorporation of pAMF facilitates near
      complete conjugation of a DBCO-PEG-monomethyl auristatin (DBCO-PEG-MMAF) drug to
      the tumor-specific, Her2-binding IgG Trastuzumab using strain-promoted azide
      alkyne cycloaddition (SPAAC) copper-free click chemistry. The resultant ADCs
      proved highly potent in in vitro cell cytotoxicity assays. 

PMID- 24437349
TI  - In situ observation of gating phenomena in the flexible porous coordination
      polymer Zn2(BPnDC)2(bpy) (SNU-9) in a combined diffraction and gas adsorption
      experiment.
AB  - The intrinsic structural dynamic during the adsorption of CO2 at 195 K and N2 at
      77 K on flexible porous coordination polymer Zn2(BPnDC)2(bpy) (SNU-9) was studied
      in situ by powder XRD. The crystal structures of as made and solvent free
      (activated) phases were determined by single crystal X-ray diffraction. During
      the structural transformation caused by activation, the rearrangement of Zn-O
      bonds occurs that leads to changes in coordination environment of Zn atoms. Such
      changes lead to the contraction of the unit cell and to decreasing unit cell
      volume of nearly 28% in comparison to the pristine as made structure. The solvent
      accessible volume of the unit cell decreases from 40.8% to 12.8%. The adsorption
      of CO2 and N2 on SNU-9 proceeds in a different way: the formation of intermediate
      phase during the CO2 adsorption could be postulated, while the transformation
      from narrow pore form to the open structure occurs in quasi-one-step in the case
      of N2 adsorption (the intermediate phase is formed only in very narrow pressure
      region). The transformation of the structure is guest dependent and the
      differences in the structures of CO2@SNU-9 at 195 K and N2@SNU-9 at 77 K were
      proven by Pawley and Rietveld refinements of powder XRD patterns. The structure
      of N2@SNU-9 is identical to this of as synthesized phase, while the structure of
      CO2@SNU-9 differs slightly. 

PMID- 24437350
TI  - Octreotide-conjugated PAMAM for targeted delivery to somatostatin receptors over
      expressed tumor cells.
AB  - PURPOSE: An octreotide-conjugated polyamidoamine (PAMAM) dendrimer was
      synthesized and employed as nanocarriers of methotrexate (MTX), for targeting to
      the somatostatin receptors over-expressed tumor cells. METHODS: PAMAM-PEG
      octreotide (PPO) and PAMAM-PEG (PPG) were synthesized and characterized. The
      cellular uptake of fluorescein isothiocyanate (FITC)-labeled PPO (PPO-FITC) and
      PPG (PPG-FITC) were investigated. The cytotoxicity of MTX and MTX nanoparticles
      were conducted in the MCF-7 cells. Besides, the pharmacokinetics studies on MTX
      nanoparticles were carried out in rats. RESULTS: The structure of PPO was
      verified by NMR detection and the diameter was 11.05 +/- 1.80 nm, with the amount
      of MTX encapsulated by PPO was 30 (molecule/molecule). MTX nanoparticles
      possessed significantly higher cytotoxicity against MCF-7 cells compared with
      free MTX, especially the PPO/MTX nanoparticles. Correspondingly, the PPO-FITC
      carrier had higher cellular uptake efficiency compared to PPG-FITC. In addition,
      pharmacokinetics studies showed that PPO/MTX nanoparticles increased mean
      residence time and bioavailability of MTX distinctly. DISCUSSION AND CONCLUSION:
      With further cellular uptake test of FITC-labeled carriers, the enhanced
      cytotoxicity of PPO/MTX nanoparticles was reasonable to ascribe to the specific
      receptor-mediated endocytosis induced by octreotide. The present study suggests
      that this PAMAM-PEG-octreotide nanocarrier opens a new path for treating cancer
      with higher efficacy.

PMID- 24437351
TI  - The involvement of reactive oxygen species derived from NADPH oxidase-1
      activation on the constitutive tyrosine auto-phosphorylation of RET proteins.
AB  - Reactive oxygen species (ROS) play a key role in neoplastic growth and tumor
      invasion is supported by various experimental data. In this study, we analyzed
      the participation of ROS in the RET tyrosine auto-phosphorylation. The NIH3T3
      cell lines transfected with cRET, MEN2A, and MEN2B individually (designated
      NIH3T3cRET, NIH3T3 RET-MEN2A, and NIH3T3RET-MEN2B) showed the elevated levels of
      intracellular ROS, and concomitantly increased Rac1 expression, as well as down
      regulation of Mn SOD and Cu/Zn SOD in comparison with the parental cell line
      expressing RET. H2O2 enhanced the constitutive tyrosine auto-phosphorylation of
      RET-MEN2A and RET-MEN2B proteins, and this increase was attenuated by treatment
      with the NOX inhibitor diphenyliodonium (DPI) or catalase. We also showed that
      DPI inhibited dimerization of RET-MEN2A. Elevated ROS derived from NOX1
      activation and downregulation of SOD in NIH3T3RET-MEN2A and NIH3T3RET-MEN 2B
      cells may be involved in RET constitutive tyrosine auto-phosphorylation, and
      scavengers of ROS such as catalase and blocking NOX1 are useful for targeting RET
      tyrosine kinase activation in cancer.

PMID- 24437352
TI  - Evaluation of Flinders Technology Associates cards for storage and molecular
      detection of avian metapneumoviruses.
AB  - The feasibility of using Flinders Technology Associates (FTA) cards for the
      molecular detection of avian metapneumovirus (aMPV) by reverse transcriptase
      polymerase chain reaction (RT-PCR) was investigated. Findings showed that no
      virus isolation was possible from aMPV-inoculated FTA cards, confirming viral
      inactivation upon contact with the cards. The detection limits of aMPV from the
      FTA card and tracheal organ culture medium were 10(1.5) median ciliostatic
      doses/ml and 10(0.75) median ciliostatic doses/ml respectively. It was possible
      to perform molecular characterization of both subtypes A and B aMPV using
      inoculated FTA cards stored for up to 60 days at 4 to 6 degrees C. Tissues of the
      turbinate, trachea and lung of aMPV-infected chicks sampled either by direct
      impression smears or by inoculation of the tissue homogenate supernatants onto
      the FTA cards were positive by RT-PCR. However, the latter yielded more
      detections. FTA cards are suitable for collecting and transporting aMPV-positive
      samples, providing a reliable and hazard-free source of RNA for molecular
      characterization. 

PMID- 24437353
TI  - In vitro fermentability of sugar beet pulp derived oligosaccharides using human
      and pig fecal inocula.
AB  - The in vitro fermentation characteristics of different classes of sugar beet
      pectic oligosaccharides (SBPOS) were studied using human and pig fecal inocula.
      The SBPOS consisted mainly of partially acetylated rhamnogalacturonan
      oligosaccharides and partially methyl-esterified/acetylated homogalacturonan
      oligosaccharides. Some SBPOS contained an unsaturated galacturonic acid residue
      at their non-reducing end. It was shown that SBPOS could be completely fermented
      by human and pig fecal microbiota, thereby producing butyrate yet mainly acetate
      and propionate as metabolites. The degradation of SBPOS by pig fecal microbiota
      was different and much slower compared to human fecal microbiota. In general,
      rhamnogalacturonan oligosaccharides were degraded slower than homogalacturonan
      oligosaccharides. Acetylation of rhamnogalacturonan oligosaccharides lowered the
      degradation rate by pig fecal microbiota but not by human fecal microbiota. No
      classic bifidogenic effect was shown for SBPOS using human fecal inoculum.
      However, several other potentially interesting modifications in the microbiota
      composition that can be associated with host health were observed, which are
      discussed. 

PMID- 24437357
TI  - Investigation into factors influencing roles, relationships, and referrals in
      integrative medicine.
AB  - INTRODUCTION: Integrative medicine (IM) is a recent phenomenon within primary
      care practice. It is defined variously as a process of integration or convergence
      of complementary and alternative medicine (CAM) with mainstream medicine or as
      the incorporation of alternative therapies into mainstream medical practice.
      Little is known about the attitude of complementary medicine practitioners
      regarding their place within this model or the factors that influence referral
      between them and medical practitioners. OBJECTIVES: The aim of this research was
      to explore practitioners' perspectives of the theory and practice of the IM
      model, relevant to factors influencing referral among them. DESIGN: This research
      applied a qualitative method with semi-structured interviews to determine
      practitioner perspectives of factors influencing referral in the IM setting. One
      family practice physician (called a general practitioner [GP] in Australia), one
      osteopath, and one naturopath were interviewed at each of two IM clinics in
      regional Australia. Thematic analysis was used to identify themes and concepts.
      RESULTS: Thematic analysis of the transcribed data allowed for an in-depth
      understanding of themes and concepts surrounding practitioner perceptions of IM.
      Predominant themes centered on the notion of interpractitioner relationships and
      collaborations. Insight into these relationships within IM revealed concepts of
      interpractitioner trust and respect. In addition, sharing a philosophy of care
      and a common understanding pertaining to scope of practice and area of expertise
      appeared to support the IM framework. These concepts and themes were determined
      as important factors influencing referrals between GPs, osteopathic physicians,
      and naturopathic practitioners in the IM clinics studied. CONCLUSION: This
      research has highlighted the significance of interprofessional relationships and
      multidisciplinary referral networks as pivotal in the efficacy of the IM clinics
      represented in this sample. Further research is needed to define the practitioner
      roles and the factors influencing referrals within IM.

PMID- 24437358
TI  - The growing problem of stranded used nuclear fuel.
AB  - By 2050, almost all U.S. nuclear reactors will have reached their 60 year maximum
      expected life. Many will shut down sooner. With no assurance that the current
      approach for finding a geologic repository or interim storage sites will succeed,
      used nuclear fuel could be stranded indefinitely at more than 70 sites in 35
      states. Societal discussions about the future of nuclear waste should be framed
      in terms of the relative risks of all alternatives. We review and compare onsite
      storage, interim storage, and a geologic repository, as well as how these
      alternatives are presented to the public. 

PMID- 24437359
TI  - [Ir(N^N^N)(C^N)L]+: a new family of luminophores combining tunability and
      enhanced photostability.
AB  - The relatively unexplored luminophore architecture [Ir(N^N^N)(C^N)L](+) (N^N^N =
      tridentate polypyridyl ligand, C^N = 2-phenylpyridine derivative, and L =
      monodentate anionic ligand) offers the stability of tridentate polypyridyl
      coordination along with the tunability of three independently variable ligands.
      Here, a new family of these luminophores has been prepared based on the
      previously reported compound [Ir(tpy)(ppy)Cl](+) (tpy = 2,2':6',2"-terpyridine
      and ppy = 2-phenylpyridine). Complexes are obtained as single stereoisomers, and
      ligand geometry is unambiguously assigned via X-ray crystallography.
      Electrochemical analysis of the materials reveals facile HOMO modulation through
      ppy functionalization and alteration of the monodentate ligand's field strength.
      Emission reflects similar modulation shifting from orange to greenish-blue upon
      replacement of chloride with cyanide. Many of the new compounds exhibit
      impressive room temperature phosphorescence with lifetimes near 3 MUs and quantum
      yields reaching 28.6%. Application of the new luminophores as photosensitizers
      for photocatalytic hydrogen generation reveals that their photostability in
      coordinating solvent is enhanced as compared to popular [Ir(ppy)2(bpy)](+) (bpy =
      2,2'-bipyridine) photosensitizers. Yet, the binding of their monodentate ligand
      emerges as a source of instability during the redox processes of cyclic
      voltammetry and mass spectrometry. DFT modeling of electronic structure is
      provided for all compounds to elucidate experimental properties. 

PMID- 24437360
TI  - A quantum dot-based immunoassay for screening of tetracyclines in bovine muscle.
AB  - A reliable and robust direct screening methodology based on a quantum dot (QD)
      fluorescent immunoassay has been developed to detect trace levels of different
      antibiotic species from the family of the tetracyclines (e.g., oxytetracycline,
      tetracycline, chlortetracycline, and doxycycline) in contaminated bovine muscle
      tissues. First, the synthesis and characterization of a new immunoprobe
      (oxytetracycline-bovine serum albumin-QD) has been carried out for its further
      application in the development of a competitive fluorescent QD-immunoassay. The
      developed fluoroimmunoassay provides sensitive and binary "yes/no" responses
      being appropriate for the screening of this family of antibiotics above or below
      a preset concentration threshold. The detection limit achieved with this
      strategy, 1 MUg/L in aqueous media and 10 MUg/kg in bovine muscle samples, is 10
      fold lower than the maximum level concentration allowed by International
      Legislation in muscle tissue, enabling suitable and efficient screening of the
      antibiotics. 

PMID- 24437363
TI  - Simultaneously efficient light absorption and charge separation in WO3/BiVO4
      core/shell nanowire photoanode for photoelectrochemical water oxidation.
AB  - We report a scalably synthesized WO3/BiVO4 core/shell nanowire photoanode in
      which BiVO4 is the primary light-absorber and WO3 acts as an electron conductor.
      These core/shell nanowires achieve the highest product of light absorption and
      charge separation efficiencies among BiVO4-based photoanodes to date and, even
      without an added catalyst, produce a photocurrent of 3.1 mA/cm(2) under simulated
      sunlight and an incident photon-to-current conversion efficiency of ~ 60% at 300
      450 nm, both at a potential of 1.23 V versus RHE.

PMID- 24437364
TI  - Metal nanoparticle based all-optical photothermal light modulator.
AB  - We present a simple scheme for the manipulation of light intensity by light
      mediated by a dissipative process. The implementation employs the heat released
      by an optically excited plasmonic metal nanoparticle to control the size of an
      isotropic bubble in a nematic liquid crystal film. The nematic film is designed
      as a zero-order half-wave plate that rotates an incident probe light polarization
      by pi/2 and is blocked by an analyzing polarizer behind the structure. The
      growing isotropic bubble disturbs the half-wave plate and causes the probe to be
      transmitted through the modulator structure. Our results demonstrate that
      dissipative processes may be advantageously used to control light by light. 

PMID- 24437368
TI  - Advances in stem-cell--generated transplantation therapy for Parkinson's disease.
AB  - INTRODUCTION: Human pluripotent stem cells have the potential to differentiate
      into different cell lineages of the human body, including dopaminergic (DA)
      neurons. Previous studies have shown that stem-cell--derived DA neurons can
      improve the motor deficits of Parkinson's disease (PD) animal models. That is why
      current research interests focus on the development of stem-cell--derived neural
      cells for transplantation therapies for PD patients. AREAS COVERED: This review
      article emphasizes the safety and efficacy requirements of human pluripotent stem
      cell--derived neural cells and usage of reliable preclinical animal models prior
      to clinical trials. The current advances and hurdles related to cell production,
      differentiation and transplantation are also summarized. EXPERT OPINION: Before
      entering the clinic, transplantable cell populations must be differentiated and
      characterized according to good manufacturing practice (GMP) regulations both in
      vitro and in vivo. Taking into account the rapid development of the stem-cell
      field and technological improvements in cell preparations and GMP facilities, we
      think that pluripotent stem-cell--derived DA neurons will offer a relevant cell
      therapy option for treatment of PD in the near future.

PMID- 24437369
TI  - Direct C-F bond formation using photoredox catalysis.
AB  - We have developed the first example of a photoredox catalytic method for the
      formation of carbon-fluorine (C-F) bonds. The mechanism has been studied using
      transient absorption spectroscopy and involves a key single-electron transfer
      from the (3)MLCT (triplet metal-to-ligand charge transfer) state of Ru(bpy)3(2+)
      to Selectfluor. Not only does this represent a new reaction for photoredox
      catalysis, but the mild reaction conditions and use of visible light also make it
      a practical improvement over previously developed UV-mediated decarboxylative
      fluorinations. 

PMID- 24437370
TI  - Application of the Taguchi method in poultry science: estimation of the in vitro
      optimum intrinsic phytase activity of rye, wheat and barley.
AB  - 1. In poultry investigations, the main interest is often to study the effects of
      many factors simultaneously. Two or three level factorial designs are the most
      commonly used for this type of investigation. However, it is often too costly to
      perform when number of factors increase. So a fractional factorial design, which
      is a subset or a fraction of a full factorial design, is an alternative. The
      Taguchi method has been proposed for simplifying and standardising fractional
      factorial designs. 2. An experiment was conducted to evaluate the applicability
      of the Taguchi method to optimise in vitro intrinsic phytase activity (IPA) of
      rye, wheat and barley under different culture conditions. 3. In order to have a
      solid base for judging the suitability of the Taguchi method, the results of the
      Taguchi method were compared with those of an experiment that was conducted as a
      3(4) full factorial arrangement with three feed ingredients (rye, wheat and
      barley), three temperatures (20 degrees C, 38 degrees C and 55 degrees C), three
      pH values (3.0, 5.5 and 8.0) and three incubation times (30, 60 and 120 min),
      with two replicates per treatment. 4. After data collection, a Taguchi L 9 (3(4))
      orthogonal array was used to estimate the effects of different factors on the
      IPA, based on a subset of only 9 instead of 81 treatments. The data were analysed
      with both Taguchi and full factorial methods and the main effects and the optimal
      combinations of these 4 factors were obtained for each method. 5. The results
      indicated that according to both the full factorial experimental design and the
      Taguchi method, the optimal culture conditions were obtained with the following
      combination: rye, pH = 3, temperature = 20  degrees C and time of incubation = 30
      min. The comparison between the Taguchi and full factorial results showed that
      the Taguchi method is a sufficient and resource saving alternative to the full
      factorial design in poultry science.

PMID- 24437371
TI  - Cadmium-free sugar-chain-immobilized fluorescent nanoparticles containing low
      toxicity ZnS-AgInS2 cores for probing lectin and cells.
AB  - Sugar chains play a significant role in various biological processes through
      sugar chain-protein and sugar chain-sugar chain interactions. To date, various
      tools for analyzing sugar chains biofunctions have been developed. Fluorescent
      nanoparticles (FNPs) functionalized with carbohydrate, such as quantum dots
      (QDs), are an attractive imaging tool for analyzing carbohydrate biofunctions in
      vitro and in vivo. Most FNPs, however, consist of highly toxic elements such as
      cadmium, tellurium, selenium, and so on, causing problems in long-term bioimaging
      because of their cytotoxicity. In this study, we developed cadmium-free sugar
      chain-immobilized fluorescent nanoparticles (SFNPs) using ZnS-AgInS2 (ZAIS) solid
      solution nanoparticles (NPs) of low or negligible toxicity as core components,
      and investigated their bioavailability and cytotoxicity. SFNPs were prepared by
      mixing our originally developed sugar-chain-ligand conjugates with ZAIS/ZnS
      core/shell NPs. In binding experiments with lectin, the obtained ZAIS/ZnS SFNPs
      interacted with an appropriate lectin to give specific aggregates, and their
      binding interaction was visually and/or spectroscopically detected. In addition,
      these SFNPs were successfully utilized for cytometry analysis and cellular
      imaging in which the cell was found to possess different sugar-binding
      properties. The results of the cytotoxicity assay indicated that SFNPs containing
      ZAIS/ZnS have much lower toxicity than those containing cadmium. These data
      strongly suggest that our designed SFNPs can be widely utilized in various
      biosensing applications involved in carbohydrates. 

PMID- 24437377
TI  - Profiling proteoforms: promising follow-up of proteomics for biomarker discovery.
AB  - Today, proteomics usually compares clinical samples by use of bottom-up profiling
      with high resolution mass spectrometry, where all protein products of a single
      gene are considered as an integral whole. At the same time, proteomics of
      proteoforms, which considers the variety of protein species, offers the potential
      to discover valuable biomarkers. Proteoforms are protein species that arise as a
      consequence of genetic polymorphisms, alternative splicing, post-translational
      modifications and other less-explored molecular events. The comprehensive
      observation of proteoforms has been an exclusive privilege of top-down
      proteomics. Here, we review the possibilities of a bottom-up approach to address
      the microheterogeneity of the human proteome. Special focus is given to shotgun
      proteomics and structure-based bioinformatics as a source of hypothetical
      proteoforms, which can potentially be verified by targeted mass spectrometry to
      determine the relevance of proteoforms to diseases. 

PMID- 24437378
TI  - Unravelling the structure of Magnus' pink salt.
AB  - A combination of multinuclear ultra-wideline solid-state NMR, powder X-ray
      diffraction (pXRD), X-ray absorption fine structure experiments, and first
      principles calculations of platinum magnetic shielding tensors has been employed
      to reveal the previously unknown crystal structure of Magnus' pink salt (MPS),
      [Pt(NH3)4][PtCl4], study the isomeric Magnus' green salt (MGS),
      [Pt(NH3)4][PtCl4], and examine their synthetic precursors K2PtCl4 and
      Pt(NH3)4Cl2.H2O. A simple synthesis of MPS is detailed which produces relatively
      pure product in good yield. Broad (195)Pt, (14)N, and (35)Cl SSNMR powder
      patterns have been acquired using the WURST-CPMG and BRAIN-CP/WURST-CPMG pulse
      sequences. Experimentally measured and theoretically calculated platinum magnetic
      shielding tensors are shown to be very sensitive to the types and arrangements of
      coordinating ligands as well as intermolecular Pt-Pt metallophilic interactions.
      High-resolution (195)Pt NMR spectra of select regions of the broad (195)Pt powder
      patterns, in conjunction with an array of (14)N and (35)Cl spectra, reveal clear
      structural differences between all compounds. Rietveld refinements of synchrotron
      pXRD patterns, guided by first principles geometry optimization calculations,
      yield the space group, unit cell parameters, and atomic positions of MPS. The
      crystal structure has P-1 symmetry and resides in a pseudotetragonal unit cell
      with a distance of >5.5 A between Pt sites in the square-planar Pt units. The
      long Pt-Pt distances and nonparallel orientation of Pt square planes prohibit
      metallophilic interactions within MPS. The combination of ultra-wideline NMR,
      pXRD, and computational methods offers much promise for future investigation and
      characterization of Pt-containing systems. 

PMID- 24437375
TI  - Factors associated with oxidative stress and cancer risk in the Breast and
      Prostate Cancer Cohort Consortium.
AB  - Both endogenous factors (genomic variations) and exogenous factors (environmental
      exposures, lifestyle) impact the balance of reactive oxygen species (ROS).
      Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome,
      manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione
      peroxidase (GPX-1; rs1050450 Pro198Leu), are purported to have functional effects
      on regulation of ROS balance. In this study, we examined associations of breast
      and prostate cancer risks and survival with these variants, and interactions
      between rs4880-rs1050450, and alcohol consumption-rs2853826. Nested case-control
      studies were conducted in the Breast and Prostate Cancer Cohort Consortium
      (BPC3), consisting of nine cohorts. The analyses included over 10726 post
      menopausal breast and 7532 prostate cancer cases with matched controls. Logistic
      regression models were used to evaluate associations with risk, and proportional
      hazard models were used for survival outcomes. We did not observe significant
      interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial
      polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34
      and 0.98, respectively) or prostate cancer (p-interaction of 0.49 and 0.50,
      respectively). We observed a weak inverse association between prostate cancer
      risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79-0.97, p = 0.01). Overall
      survival among women with breast cancer was inversely associated with G10398
      carriers who consumed alcohol (HR 0.66 95% CI 0.49-0.88). Given the high power in
      our study, it is unlikely that interactions tested have more than moderate
      effects on breast or prostate cancer risk. Observed associations need both
      further epidemiological and biological confirmation.

PMID- 24437380
TI  - Nonlocal response of metallic nanospheres probed by light, electrons, and atoms.
AB  - Inspired by recent measurements on individual metallic nanospheres that cannot be
      explained with traditional classical electrodynamics, we theoretically
      investigate the effects of nonlocal response by metallic nanospheres in three
      distinct settings: atomic spontaneous emission, electron energy loss
      spectroscopy, and light scattering. These constitute two near-field and one far
      field measurements, with zero-, one-, and two-dimensional excitation sources,
      respectively. We search for the clearest signatures of hydrodynamic pressure
      waves in nanospheres. We employ a linearized hydrodynamic model, and Mie-Lorenz
      theory is applied for each case. Nonlocal response shows its mark in all three
      configurations, but for the two near-field measurements, we predict especially
      pronounced nonlocal effects that are not exhibited in far-field measurements.
      Associated with every multipole order is not only a single blueshifted surface
      plasmon but also an infinite series of bulk plasmons that have no counterpart in
      a local-response approximation. We show that these increasingly blueshifted
      multipole plasmons become spectrally more prominent at shorter probe-to-surface
      separations and for decreasing nanosphere radii. For selected metals, we predict
      hydrodynamic multipolar plasmons to be measurable on single nanospheres. 

PMID- 24437384
TI  - Synthesis, characterization, and photophysical properties of Bodipy-spirooxazine
      and -spiropyran conjugates: modulation of fluorescence resonance energy transfer
      behavior via acidochromic and photochromic switching.
AB  - Two series of Bodipy-containing photochromic spirooxazine and spiropyran
      derivatives have been designed, synthesized and characterized by (1)H NMR, ESI
      mass spectrometry and elemental analysis. Their electrochemical and photochromic
      properties were investigated. The photophysical, ultrafast transient absorption,
      and fluorescence resonance energy transfer (FRET) properties from Bodipy (donor)
      to the ring-opened merocyanine (acceptor) were also studied. Upon
      photoexcitation, all the photochromic spirooxazine- and spiropyran-containing
      compounds exhibited reversible photochromism. Computational studies have been
      performed to provide further insights into the nature of the electronic
      transitions for the two classes of compounds. The rate constants and activation
      parameters for thermal bleaching reactions of compounds SO, SP-alkyne, 1-3, and 8
      10 were determined through kinetic studies in acetonitrile. The thermal bleaching
      reaction rate of the spiropyran-containing compounds is found to be much slower
      than that of the spirooxazine-containing counterparts. 

PMID- 24437381
TI  - Effect of copper oxide concentration on the formation and persistency of
      environmentally persistent free radicals (EPFRs) in particulates.
AB  - Environmentally persistent free radicals (EPFRs) are formed by the chemisorption
      of substituted aromatics on metal oxide surfaces in both combustion sources and
      superfund sites. The current study reports the dependency of EPFR yields and
      their persistency on metal loading in particles (0.25, 0.5, 0.75, 1, 2, and 5%
      CuO/silica). The EPFRs were generated through exposure of particles to three
      adsorbate vapors at 230  degrees C: phenol, 2-monochlorophenol (2-MCP), and
      dichlorobenzene (DCBz). Adsorption resulted in the formation of surface-bound
      phenoxyl- and semiquinoine-type radicals with characteristic EPR spectra
      displaying a g value ranging from ~ 2.0037 to 2.006. The highest EPFR yield was
      observed for CuO concentrations between 1 and 3% in relation to MCP and phenol
      adsorption. However, radical density, which is expressed as the number of
      radicals per copper atom, was highest at 0.75-1% CuO loading. For 1,2
      dichlorobenzene adsorption, radical concentration increased linearly with
      decreasing copper content. At the same time, a qualitative change in the radicals
      formed was observed--from semiquinone to chlorophenoxyl radicals. The two longest
      lifetimes, 25 and 23 h, were observed for phenoxyl-type radicals on 0.5% CuO and
      chlorophenoxyl-type radicals on 0.75% CuO, respectively.

PMID- 24437386
TI  - Nonenzymatic polyubiquitination of expressed proteins.
AB  - Ubiquitination is one of the most ubiquitous posttranslational modifications in
      eukaryotes and is involved in various cellular events such as proteasomal
      degradation and DNA repair. The overwhelming majority of studies aiming to
      understand ubiquitination and deubiquitination have employed unanchored ubiquitin
      chains and mono-ubiquitinated proteins. To shed light on these processes at the
      molecular level, it is crucial to have facile access to ubiquitin chains linked
      to protein substrates. Such conjugates are highly difficult to prepare
      homogenously and in workable quantities using the enzymatic machinery. To address
      this formidable challenge we developed new chemical approaches to covalently
      attach ubiquitin chains to a protein substrate through its Cys residue. A key
      aspect of this approach is the installation of acyl hydrazide functionality at
      the C-terminus of the proximal Ub, which allows, after ubiquitin chain assembly,
      the introduction of various reactive electrophiles for protein conjugation.
      Employing alpha-globin as a model substrate, we demonstrate the facile
      conjugation to K48-linked ubiquitin chains, bearing up to four ubiquitins,
      through disulfide and thioether linkages. These bioconjugates were examined for
      their behavior with the USP2 enzyme, which was found to cleave the ubiquitin
      chain in a similar manner to unanchored ones. Furthermore, proteasomal
      degradation study showed that di-ubiquitinated alpha-globin is rapidly degraded
      in contrast to the mono-ubiquitinated counterpart, highlighting the importance of
      the chain lengths on proteasomal degradation. The present work opens
      unprecedented opportunities in studying the ubiquitin signal by enabling access
      to site-specifically polyubiquitinated proteins with an increased size and
      complexity. 

PMID- 24437387
TI  - Preventing chronic disease through improving food and activity environments.

PMID- 24437392
TI  - Phase diagram of quasi-two-dimensional carbon, from graphene to diamond.
AB  - We explore how a few-layer graphene can undergo phase transformation into thin
      diamond film under reduced or no pressure, if the process is facilitated by
      hydrogenation of the surfaces. Such a "chemically induced phase transition" is
      inherently nanoscale phenomenon, when the surface conditions directly affect
      thermodynamics, and the transition pressure depends greatly on film thickness.
      For the first time we obtain, by ab initio computations of the Gibbs free energy,
      a phase diagram (P, T, h) of quasi-two-dimensional carbon-diamond film versus
      multilayered graphene. It describes accurately the role of film thickness h and
      shows the feasibility of creating novel quasi-two-dimensional materials. Further,
      the role of finite diameter of graphene flakes and possible formation of the
      diamond films with the (110) surface are described as well. 

PMID- 24437393
TI  - Structural and electronic properties of micellar Au nanoparticles: size and
      ligand effects.
AB  - Gaining experimental insight into the intrinsic properties of nanoparticles (NPs)
      represents a scientific challenge due to the difficulty of deconvoluting these
      properties from various environmental effects such as the presence of adsorbates
      or a support. A synergistic combination of experimental and theoretical tools,
      including X-ray absorption fine-structure spectroscopy, scanning transmission
      electron microscopy, atomic force microscopy, and density functional theory was
      used in this study to investigate the structure and electronic properties of
      small (~1-4 nm) Au NPs synthesized by an inverse micelle encapsulation method.
      Metallic Au NPs encapsulated by polystyrene 2-vinylpiridine (PS-P2VP) were
      studied in the solution phase (dispersed in toluene) as well as after deposition
      on gamma-Al2O3. Our experimental data revealed a size-dependent contraction of
      the interatomic distances of the ligand-protected NPs with decreasing NP size.
      These findings are in good agreement with the results from DFT calculations of
      unsupported Au NPs surrounded by P2VP, as well as those obtained for pure (ligand
      free) Au clusters of analogous sizes. A comparison of the experimental and
      theoretical results supports the conclusion that the P2VP ligands employed to
      stabilize the gold NPs do not lead to strong distortions in the average
      interatomic spacing. The changes in the electronic structure of the Au-P2VP NPs
      were found to originate mainly from finite size effects and not from charge
      transfer between the NPs and their environment (e.g., Au-ligand interactions). In
      addition, the isolated ligand-protected experimental NPs only display a weak
      interaction with the support, making them an ideal model system for the
      investigation of size-dependent physical and chemical properties of structurally
      well-defined nanomaterials. 

PMID- 24437396
TI  - Conductance of tailored molecular segments: a rudimentary assessment by Landauer
      formulation.
AB  - One of the strengths of molecular electronics is the synthetic ability of tuning
      the electric properties by the derivatization and reshaping of the functional
      moieties. However, after the quantitative measurements of single-molecule
      resistance became available, it was soon apparent that the assumption of
      negligible influence of the headgroup-electrode contact on the molecular
      resistance was oversimplified. Due to the measurement scheme of the metal-
      molecule-metal configuration, the contact resistance is always involved in the
      reported values. Consequently the electrical behavior of the tailored molecular
      moiety can only be conceptually inferred by the tunneling decay constant (betan
      in Rmeasured = R(n=0)e(betanN), where N is the number of repeated units),
      available only for compounds with a homologous series. This limitation hampers
      the exploration of novel structures for molecular devices. Based on the Landauer
      formula, we propose that the single-molecule resistance of the molecular
      backbones can be extracted. This simplified evaluation scheme is cross-examined
      by electrode materials of Au, Pd, and Pt and by anchoring groups of thiol (-SH),
      nitrile (-CN), and isothiocyanate (-NCS). The resistance values of molecular
      backbones for polymethylenes (n = 4, 6, 8, and 10) and phenyl (-C6H4-) moieties
      are found independent of the anchoring groups and electrode materials. The
      finding justifies the proposed approach that the resistance of functional
      moieties can be quantitatively evaluated from the measured values even for
      compounds without repeated units.

PMID- 24437397
TI  - The lung microbiome. A new frontier in pulmonary medicine: introduction and
      perspective.

PMID- 24437398
TI  - Environmental microorganisms and lung health.

PMID- 24437399
TI  - Technology and techniques for microbial ecology via DNA sequencing.
AB  - High-throughput sequencing technology, coupled with the use of conserved marker
      genes, has allowed for the understanding of communities of microbes (both
      culturable and unculturable) as well as their phylogenetic placement. The recent
      explosion of sequencing data prompted the development of software that could
      process the vast amount of data generated and phylogenetically differentiate
      groups of samples. Host-associated microbial studies have revealed that microbes
      are highly varied between individuals and fluctuate within an individual. Large
      scale studies are being undertaken that include collection of extensive
      environmental data to help uncover the forces that shape microbial communities. 

PMID- 24437400
TI  - A brave new world: the lung microbiota in an era of change.
AB  - The development of culture-independent techniques has revolutionized our
      understanding of how our human cells interact with the even greater number of
      microbial inhabitants of our bodies. As part of this revolution, data are
      increasingly challenging the old dogma that in health, the lung mucosa is
      sterile. To understand how the lung microbiome may play a role in human health,
      we identified five major questions for lung microbiome research: (1) Is the lung
      sterile? (2) Is there a unique core microbiome in the lung? (3) How dynamic are
      the microbial populations? (4) How do pulmonary immune responses affect
      microbiome composition? and (5) Are the lungs influenced by the intestinal immune
      responses to the gut microbiome? From birth, we are exposed to continuous
      microbial challenges that shape our microbiome. In our changing environment,
      perturbation of the gut microbiome affects both human health and disease. With
      widespread antibiotic use, the ancient microbes that formerly resided within us
      are being lost, for example, Helicobacter pylori in the stomach. Animal models
      show that antibiotic exposure in early life has developmental consequences.
      Considering the potential effects of this altered microbiome on pulmonary
      responses will be critical for future investigations. 

PMID- 24437401
TI  - Mucosal immunity and the microbiome.
AB  - By definition, the mucosal immune system is responsible for interfacing with the
      outside world, specifically responding to external threats, of which pathogenic
      microbes represent a primary challenge. However, it has become apparent that the
      human host possesses a numerically vast and taxonomically diverse resident
      microbiota, predominantly in the gut, and also in the airway, genitourinary
      tract, and skin. The microbiota is generally considered symbiotic, and has been
      implicated in the regulation of cellular growth, restitution after injury,
      maintenance of barrier function, and importantly, in the induction, development,
      and modulation of immune responses. The mucosal immune system uses diverse
      mechanisms that protect the host from overt pathogens, but necessarily has
      coevolved to monitor, nurture, and exploit the normal microbiota. As a whole,
      mucosal immunity encompasses adaptive immune regulation that can involve systemic
      processes, local tissue-based innate and inflammatory events, intrinsic defenses,
      and highly conserved cell autonomous cytoprotective responses. Interestingly,
      specific taxa within the normal microbiota have been implicated in roles shaping
      specific adaptive, innate, and cell autonomous responses. Taken together, the
      normal microbiota exerts profound effects on the mucosal immune system, and
      likely plays key roles in human physiology and disease. 

PMID- 24437402
TI  - ABCs of the lung microbiome.
AB  - The lungs of healthy humans have traditionally been considered to be sterile when
      examined by culture-based techniques. However, molecular identification
      techniques are now being used to explore the lung microbiome in ways that mirror
      study of other body sites and organ systems. Familiarity with population
      definitions and indices of diversity will lead to better understanding of the
      literature now coming to publication. Differences in methodology and sampling may
      contribute significantly to experimental variability, and the field has not
      coalesced around standard ways to present data or to perform statistical
      comparisons. This emerging and exciting field of investigation is leading to new
      ways of thinking about the lung and about lung disease. 

PMID- 24437403
TI  - Probiotics and lung immune responses.
AB  - There is increasing interest in the potential for microbe-based therapeutic
      approaches to asthma and respiratory infection. However, to date, clinical trials
      of probiotics in the treatment of respiratory disease have met with limited
      success. It is becoming clear that to identify the true therapeutic potential of
      microbes we must move away from a purely empirical approach to clinical trials
      and adopt knowledge-based selection of candidate probiotics strains, dose, and
      means of administration. Animal models have played a key role in the
      identification of mechanisms underlying the immunomodulatory capacity of specific
      bacteria. Microbe-induced changes in dendritic cell phenotype and function appear
      key to orchestrating the multiple pathways, involving inter alia, T cells,
      natural killer cells, and alveolar macrophages, associated with the protective
      effect of probiotics. Moving forward, the development of knowledge-based
      strategies for microbe-based therapeutics in respiratory disease will be aided by
      greater understanding of how specific bacterial structural motifs activate unique
      combinations of pattern recognition receptors on dendritic cells and thus direct
      desired immune responses. 

PMID- 24437404
TI  - Cigarette smoke effects on innate immune mechanisms in the nasal mucosa.
      Potential effects on the microbiome.
AB  - It is well established that exposure to cigarette smoke (CS), through active
      smoking and through exposure to secondhand smoke, has immunosuppressive effects,
      yet how this might affect the microbiome is not known. In this manuscript we
      focus on the effects of CS on innate host defense response, with particular
      emphasis on the role of epithelial cells and mucosal immune responses in the nose
      and the potential effects on the microbiome. The studies described here briefly
      summarize the effects of CS on specific innate immune cells, such as neutrophils,
      macrophages/monocytes, natural killer cells, and dendritic cells. A detailed
      description of how CS affects epithelial cells and why we consider this to be a
      central defect in the overall immunosuppressive effects of CS in the lung is
      provided. We summarize data on the role of the "epimmunome" in the context of CS
      exposure, including the effects on soluble mediator production, such as
      cytokines, chemokines, and antimicrobial defense mediators. Separate emphasis is
      put on the expression of ligands on epithelial cells, which directly interact
      with receptors on immune cells, and the effects of CS on these interactions. We
      introduce the nose and nasal mucosa as a model to study the effects of CS
      exposure on host defense responses and changes in the microbiome in humans in
      vivo. Understanding the dynamics of a healthy microbiome and how CS affects this
      balance is important to uncovering the mechanisms of CS-induced disease. 

PMID- 24437405
TI  - Chronic obstructive pulmonary disease and infection. Disruption of the
      microbiome?
AB  - The dynamics of infection in chronic obstructive pulmonary disease (COPD) are
      complex, and microbiome technology has provided us with a new research tool for
      its better understanding. There is compartmentalization of the microbiota in the
      various parts of the lung. Studies of the lower airway lumen microbiota in COPD
      have yielded confusing results, and additional studies with scrupulous attention
      to prevent and account for upper airway contamination of bronchoalveolar lavage
      samples are required. Lung tissue microbiota has been examined in three studies,
      which also demonstrate varied results based on the site of sampling (bronchial
      mucosa, lung parenchyma), and this variation extends to sampling sites within a
      lobe of the lung. The Vicious Circle Hypothesis embodies how an altered lung
      microbiome could contribute to COPD progression. Relating microbiota composition
      to airway and systemic inflammation and clinical outcomes are important research
      questions. Although various obstacles need to be surmounted, ultimately lung
      microbiome studies will provide new insights into how infection contributes to
      COPD. 

PMID- 24437406
TI  - The microbiome and asthma.
AB  - That the subglottic airways are not sterile, as was once believed, but are
      populated by a distinct "bronchial microbiome," is now accepted. Also accepted is
      the concept that asthma is associated with differences in the composition of this
      microbiome. What is not clear is whether the differences in microbial community
      composition themselves mediate pathologic changes in the airways or whether they
      reflect differences in systemic immune function driven by differences in the
      development of the gastrointestinal microbiome in early life, when the immune
      system is most malleable. Recognition of the probable existence of a "common
      mucosal immune system" allowed synthesis of these apparently opposing ideas into
      a single conceptual model. Gastrointestinal microbiome-driven differences in
      systemic immune function predispose to sensitization to allergens deposited on
      mucosal surfaces, whereas possibly similar, but not identical, differences in
      immune function predispose to less effective responses to microbial infection of
      the airways, resulting in persistence of the inflammation underlying the
      structural and functional abnormalities of asthma. In this model, allergic
      sensitization and asthma are thus seen as commonly overlapping but not
      necessarily coincident consequences of abnormalities in microbial colonization,
      development of immune function, and encounter with agents infecting the
      respiratory tract. 

PMID- 24437407
TI  - Heart-lung interaction via infection.
AB  - Lung and cardiovascular disease are increasingly recognized to occur in the same
      patient populations. Infections, either through stimulation of inflammation or
      through direct infection, can lead to end-organ damage and have been postulated
      as a potential link between lung and cardiovascular diseases. Mechanisms by which
      infections may link lung and cardiac diseases include effects of systemic
      infections, microbial translocation of pathogens from the gastrointestinal tract
      or other sites, damaging effects of metabolic products, or influences of smoking
      on the microbiome. Other mechanisms, such as alterations in the local microbiome,
      environmental exposures, or immune regulation by microbial communities, may be
      important. These relationships are likely quite complex, with multiple routes
      between infection and disease possible. A better understanding of the links of
      infection to lung and heart disease can improve our understanding of the
      pathogenesis of these disorders and uncover novel therapeutic approaches. 

PMID- 24437408
TI  - Viruses and microbiome alterations.
AB  - Viral infection represents a common and problematic health care issue,
      particularly in younger and senior populations. The respiratory tract is a major
      portal for microbial exposure, where viral infection can result in
      nonsymptomatic, mild, and self-limiting or severe and sometimes fatal infection.
      Although it is well established that virus-specific properties, such as longevity
      and replication kinetics, impact clinical manifestations, it is less well
      understood why distinct infectious outcomes may occur across a population of
      individuals infected with the same strain of virus. Emerging evidence points to
      interpersonal variation in pulmonary and gastrointestinal microbiome composition,
      and specifically to members of the Lactobacillus genus, as key components in
      defining respiratory viral infection outcomes. Moreover, human studies of airway
      microbiota after pH1N1 demonstrate that the composition of the respiratory
      microbiome can be modified by viral infection in a manner that enriches for
      pathogens associated with secondary bacterial infection. In this article, current
      knowledge in the field of human microbiome research, particularly as it pertains
      to respiratory viral infection, is reviewed. 

PMID- 24437409
TI  - The cystic fibrosis lung microbiome.
AB  - The chronic colonization of the lower airways by bacterial pathogens is the
      leading cause of morbidity and mortality in patients with cystic fibrosis (CF).
      Pseudomonas aeruginosa is the most common CF pathogen, followed by Staphylococcus
      aureus. Improvements in airway clearance and more effective treatment of the
      conventional CF pathogens has led to the emergence of new airway pathogens such
      as Stenotrophomonas maltophilia, Mycobacterium abscessus, and Achromobacter. More
      recently, it has become appreciated that the lower airways in patients with CF
      are colonized by a more complex polymicrobial community composed primarily of
      bacteria found in the upper respiratory tract. This includes obligate anaerobes,
      most commonly Prevotella. Expanded culturing methods and culture-independent
      molecular methods are being used to characterize the composition and dynamics of
      these polymicrobial communities in patients with CF. The contribution of the CF
      microbiome to airway disease is actively being investigated and will present new
      opportunities for disease management in CF. However, there remain many challenges
      that must be overcome if microbiome profiling is going to inform clinical
      practice. 

PMID- 24437410
TI  - The lung microbiome. A new frontier in pulmonary medicine.

PMID- 24437411
TI  - The human microbiome. Early life determinant of health outcomes.
AB  - The development of new technologies to isolate and identify microbial genomes has
      markedly increased our understanding of the role of microbiomes in health and
      disease. The idea, first proposed as part of the hygiene hypothesis, that
      environmental microbes influence the developmental trajectories of the immune
      system in early life, has now been considerably extended and refined. The
      abundant microbiota present in mucosal surfaces, especially the gut, is actively
      selected by the host through complex receptor systems that respond differentially
      depending on the molecular patterns presented to mucosal cells. Germ-free mice
      are more likely to develop allergic airway inflammation and show alterations in
      normal motor control and anxiety. These effects can be reversed by neonatal
      microbial recolonization but remain unchanged if recolonization occurs in adults.
      What emerges from these recent studies is the discovery of a complex, major early
      environmental determinant of lifetime human phenotypes. To change the natural
      course of asthma, obesity, and other chronic inflammatory conditions, active
      manipulation of the extensive bacterial, phage, and fungal metagenomes present in
      mucosal surfaces may be required, specifically during the developing years.
      Domesticating the human microbiome and adapting it to our health needs may be a
      challenge akin to, but far more complex than, the one faced by humanity when a
      few dozen species of plants and animals were domesticated during the transition
      between hunter-gatherer and sedentary societies after the end of the Pleistocene
      era. 

PMID- 24437431
TI  - Novel polyhydroxylated steroids from the East China Sea gorgonian Echinogorgia
      sassapo reticulata with suppressive activity of leukotriene C4 generation and
      degranulation in bone marrow-derived mast cells.
AB  - The gorgonian Echinogorgia sassapo reticulata contains two new bioactive
      polyhydroxylated steroids, sassapols A (1), B (2), and five related known
      compounds (3-7). Compound 6 has been encountered for the first time in natural
      sources. The structures of these new compounds were defined by spectroscopic
      analysis. All the compounds (1-7) isolated from E. sassapo reticulata were tested
      for anti-inflammatory activity. Compounds 1, 3, 5, and 7 inhibited both the
      generation of leukotriene C4 and the degranulation reaction in mouse bone marrow
      derived mast cells.

PMID- 24437432
TI  - Improving care for depression and suicide risk in adolescents: innovative
      strategies for bringing treatments to community settings.
AB  - This article reviews the literature on interventions and services for depression
      and suicide prevention among adolescents, with the goals of placing this science
      within the context of currently changing health care environments and
      highlighting innovative models for improving health and mental health. We examine
      the challenges and opportunities offered by new initiatives and legislation
      designed to transform the US health and mental health care systems; summarize
      knowledge regarding the treatment of depression and suicidality/self-harm in
      adolescents; and describe innovative models for partnering with health systems
      and communities. This review demonstrates that treatment models and service
      delivery strategies are currently available for increasing evidence-based care,
      particularly for depression, and concludes with recommendations for future
      research and quality improvement initiatives aimed at inspiring additional
      efforts to put science to work, bridge science and community practice, and
      develop strategies for partnering with communities to improve care, mental
      health, and well-being among adolescents. 

PMID- 24437434
TI  - Justice policy reform for high-risk juveniles: using science to achieve large
      scale crime reduction.
AB  - After a distinctly punitive era, a period of remarkable reform in juvenile crime
      regulation has begun. Practical urgency has fueled interest in both crime
      reduction and research on the prediction and malleability of criminal behavior.
      In this rapidly changing context, high-risk juveniles--the small proportion of
      the population where crime becomes concentrated--present a conundrum. Research
      indicates that these are precisely the individuals to treat intensively to
      maximize crime reduction, but there are both real and imagined barriers to doing
      so. Mitigation principles (during early adolescence, ages 10-13) and
      institutional placement or criminal court processing (during mid-late
      adolescence, ages 14-18) can prevent these juveniles from receiving interventions
      that would best protect public safety. In this review, we synthesize relevant
      research to help resolve this challenge in a manner that is consistent with the
      law's core principles. In our view, early adolescence offers unique opportunities
      for risk reduction that could (with modifications) be realized in the juvenile
      justice system in cooperation with other social institutions.

PMID- 24437433
TI  - Emotional and behavioral symptoms in neurodegenerative disease: a model for
      studying the neural bases of psychopathology.
AB  - Disruptions in emotional, cognitive, and social behavior are common in
      neurodegenerative disease and in many forms of psychopathology. Because
      neurodegenerative diseases have patterns of brain atrophy that are much clearer
      than those of psychiatric disorders, they may provide a window into the neural
      bases of common emotional and behavioral symptoms. We discuss five common
      symptoms that occur in both neurodegenerative disease and psychopathology (i.e.,
      anxiety, dysphoric mood, apathy, disinhibition, and euphoric mood) and their
      associated neural circuitry. We focus on two neurodegenerative diseases (i.e.,
      Alzheimer's disease and frontotemporal dementia) that are common and well
      characterized in terms of emotion, cognition, and social behavior and in patterns
      of associated atrophy. Neurodegenerative diseases provide a powerful model system
      for studying the neural correlates of psychopathological symptoms; this is
      supported by evidence indicating convergence with psychiatric syndromes (e.g.,
      symptoms of disinhibition associated with dysfunction in orbitofrontal cortex in
      both frontotemporal dementia and bipolar disorder). We conclude that
      neurodegenerative diseases can play an important role in future approaches to the
      assessment, prevention, and treatment of mental illness. 

PMID- 24437436
TI  - The contribution of cultural competence to evidence-based care for ethnically
      diverse populations.
AB  - Despite compelling arguments for the dissemination of evidence-based treatments
      (EBTs), questions regarding their relevance to ethnically diverse populations
      remain. This review summarizes what is known about psychotherapy effects with
      ethnic minorities, with a particular focus on the role of cultural competence
      when implementing EBTs. Specifically, we address three questions: (a) does
      psychotherapy work with ethnic minorities, (b) do psychotherapy effects differ by
      ethnicity, and (c) does cultural tailoring enhance treatment effects? The
      evidence suggests that psychotherapy is generally effective with ethnic
      minorities, and treatment effects are fairly robust across cultural groups and
      problem areas. However, evidence for cultural competence is mixed. Ethnic
      minority-focused treatments frequently incorporate culturally tailored
      strategies, and these tailored treatments are mostly efficacious; yet support for
      cultural competence as a useful supplement to standard treatment remains
      equivocal at best. We also discuss research limitations, areas for future
      research, and clinical implications. 

PMID- 24437445
TI  - Anchoring a molecular iron catalyst to solar-responsive WO3 improves the rate and
      selectivity of photoelectrochemical water oxidation.
AB  - Molecular catalysts help overcome the kinetic limitations of water oxidation and
      generally result in faster rates for water oxidation than do heterogeneous
      catalysts. However, molecular catalysts typically function in the dark and
      therefore require sacrificial oxidants such as Ce(4+) or S2O8(2-) to provide the
      driving force for the reaction. In this Communication, covalently anchoring a
      phosphonate-derivatized complex, Fe(tebppmcn)Cl2 (1), to WO3 removes the need for
      a sacrificial oxidant and increases the rate of photoelectrochemical water
      oxidation on WO3 by 60%. The dual-action catalyst, 1-WO3, also gives rise to
      increased selectivity for water oxidation in pH 3 Na2SO4 (56% on bare WO3, 79% on
      1-WO3). This approach provides promising alternative routes for solar water
      oxidation. 

PMID- 24437446
TI  - Steered molecular dynamics simulations for studying protein-ligand interaction in
      cyclin-dependent kinase 5.
AB  - In this study, we applied steered molecular dynamics (SMD) simulations to
      investigate the unbinding mechanism of nine inhibitors of the enzyme cyclin
      dependent kinase 5 (CDK5). The study had two major objectives: (i) to create a
      correlation between the unbinding force profiles and the inhibition activities of
      these compounds expressed as IC50 values; (ii) to investigate the unbinding
      mechanism and to reveal atomistic insights, which could help identify accessory
      binding sites and transient interactions. Overall, we carried out 1.35 MUs of
      cumulative SMD simulations. We showed that SMD could qualitatively discriminate
      binders from nonbinders, while it failed to properly rank series of inhibitors,
      particularly when IC50 values were too similar. From a mechanistic standpoint,
      SMD provided useful insights related to transient and dynamical interactions,
      which could complement static description obtained by X-ray crystallography
      experiments. In conclusion, the present study represents a further step toward a
      systematic exploitation of SMD and other dynamical approaches in structure-based
      drug design and computational medicinal chemistry. 

PMID- 24437447
TI  - Telegraphic noise in transport through colloidal quantum dots.
AB  - We report measurements of electrical transport through single CdSe/CdS core/shell
      colloidal quantum dots (cQDs) connected to source and drain contacts. We observe
      telegraphic switching noise showing few plateaus at room temperature. We model
      and interpret these results as charge trapping of individual trap states, and
      therefore we resolve individual charge defects in these high-quality low-strain
      cQDs. The small number of observed defects quantitatively validates the
      passivation method based on thick CdS shells nearly lattice-matched to CdSe cores
      first developed to suppress photoluminescence blinking. Finally, we introduce a
      figure of merit useful to efficiently distinguish telegraphic noise from noise
      with a Gaussian distribution. 

PMID- 24437448
TI  - Supported polytertiary amines: highly efficient and selective SO2 adsorbents.
AB  - Tertiary amine containing poly(propyleneimine) second (G2) and third (G3)
      generation dendrimers as well as polyethyleneimine (PEI) were developed for the
      selective removal of SO2. N-Alkylation of primary and secondary amines into
      tertiary amines was confirmed by FTIR and NMR analysis. Such modified polyamines
      were impregnated on two nanoporous supports, namely, SBA-15PL silica with
      platelet morphology and ethanol-extracted pore-expanded MCM-41 (PME) composite.
      In the presence of 0.1% SO2/N2 at 23  degrees C, the uptake of modified PEI, G2,
      and G3 supported on SBA-15PL was 2.07, 2.35, and 1.71 mmol/g, respectively;
      corresponding to SO2/N ratios of 0.22, 0.4, and 0.3. Under the same conditions,
      the SO2 adsorption capacity of PME-supported modified PEI and G3 was
      significantly higher, reaching 4.68 and 4.34 mmol/g, corresponding to SO2/N
      ratios of 0.41 and 0.82, respectively. The working SO2 adsorption capacity
      decreased with increasing temperature, reflecting the exothermic nature of the
      process. The adsorption capacity of these materials was enhanced dramatically in
      the presence of humidity in the gas mixture. FTIR data before SO2 adsorption and
      after adsorption and regeneration did not indicate any change in the materials.
      Nonetheless, the SO2 working capacity decreased in consecutive
      adsorption/regeneration cycles due to evaporation of impregnated polyamines,
      rather than actual deactivation. FTIR and (13)C and (15)N CP-MAS NMR of fresh and
      SO2 adsorbed modified G3 on PME confirmed the formation of a complexation adduct.

PMID- 24437435
TI  - Attention-deficit/hyperactivity disorder and risk of substance use disorder:
      developmental considerations, potential pathways, and opportunities for research.
AB  - Many opportunities to explain attention-deficit/hyperactivity disorder (ADHD)
      related risk of substance use disorder (SUD) remain available for study. We
      detail these opportunities by considering characteristics of children with ADHD
      and factors affecting their outcomes side by side with overlapping variables in
      the developmental literature on SUD etiology. Although serious conduct problems
      are a known contributor to ADHD-related risk of SUD, few studies have considered
      their emergence developmentally and in relation to other candidate mediators and
      moderators that could also explain risk and be intervention targets. Common ADHD
      related impairments, such as school difficulties, are in need of research.
      Heterogeneous social impairments have the potential for predisposing, and
      buffering, influences. Research on neurocognitive domains should move beyond
      standard executive function batteries to measure deficits in the interface
      between cognitive control, reward, and motivation. Ultimately, maximizing
      prediction will depend, as it has in the SUD literature, on simultaneous
      consideration of multiple risk factors. 

PMID- 24437450
TI  - Persistent topological surface state at the interface of Bi2Se3 film grown on
      patterned graphene.
AB  - We employed graphene as a patternable template to protect the intrinsic surface
      states of thin films of topological insulators (TIs) from environment. Here we
      find that the graphene provides high-quality interface so that the Shubnikov de
      Haas (SdH) oscillation associated with a topological surface state could be
      observed at the interface of a metallic Bi2Se3 film with a carrier density higher
      than ~ 10(19) cm(-3). Our in situ X-ray diffraction study shows that the Bi2Se3
      film grows epitaxially in a quintuple layer-by-layer fashion from the bottom
      layer without any structural distortion by interfacial strain. The
      magnetotransport measurements including SdH oscillations stemming from multiple
      conductance channels reveal that the topological surface state, with the mobility
      as high as ~ 0.5 m(2)/(V s), remains intact from the graphene underneath without
      degradation. Given that the graphene was prepatterned on arbitrary insulating
      substrates, the TI-based microelectronic design could be exploited. Our study
      thus provides a step forward to observe the topological surface states at the
      interface without degradation by tuning the interface between TI and graphene
      into a measurable current for device application.

PMID- 24437451
TI  - How alkyl halide structure affects E2 and SN2 reaction barriers: E2 reactions are
      as sensitive as SN2 reactions.
AB  - High-level electronic structure calculations, including a continuum treatment of
      solvent, are employed to elucidate and quantify the effects of alkyl halide
      structure on the barriers of SN2 and E2 reactions. In cases where such
      comparisons are available, the results of these calculations show close agreement
      with solution experimental data. Structural factors investigated include alpha-
      and beta-methylation, adjacency to unsaturated functionality (allyl, benzyl,
      propargyl, alpha to carbonyl), ring size, and alpha-halogenation and cyanation.
      While the influence of these factors on SN2 reactivity is mostly well-known, the
      present study attempts to provide a broad comparison of both SN2 and E2
      reactivity across many cases using a single methodology, so as to quantify
      relative reactivity trends. Despite the fact that most organic chemistry
      textbooks say far more about how structure affects SN2 reactions than about how
      it affects E2 reactions, the latter are just as sensitive to structural variation
      as are the former. This sensitivity of E2 reactions to structure is often
      underappreciated. 

PMID- 24437456
TI  - Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary
      carcinoma of the large intestine.
AB  - CONTEXT: Distinction of medullary carcinoma of the large intestine from other
      cytokeratin (CK) 7-/CK20- carcinomas can be challenging when working on a tumor
      of unknown primary because the majority of medullary carcinomas are negative for
      CK7, CK20, and CDX2. OBJECTIVE: To investigate the expression of cadherin-17 and
      SATB-2 and other markers in medullary carcinomas of the large intestine and
      cadherin-17 and SATB2 in a large number of carcinomas and normal tissues from
      various organs to further test their diagnostic specificity. DESIGN: This study
      evaluated cadherin-17 and SATB2 expression in 18 medullary carcinoma cases and
      1941 tumors and 358 normal tissues from various organs. Other immunomarkers,
      including MLH1, PMS2, MSH2, MSH6, CDX2, CK7, CK20, TFF3, MUC4, calretinin, p504S,
      villin, and synaptophysin, were also tested on the 18 medullary carcinoma cases.
      RESULTS: The results demonstrated (1) loss of MLH1 and PMS2 in more than 80% of
      medullary carcinomas; (2) expression of cadherin-17 and SATB2 in 89% of medullary
      carcinomas; (3) focal expression of TFF3, MUC4, calretinin, CDX2, CK20, and
      synaptophysin in 72%, 72%, 67%, 67%, 28%, and 17% of 18 medullary carcinoma
      cases, respectively; and (4) expression of SATB2 and cadherin-17 in 97% and 98%
      of the colorectal adenocarcinomas, respectively, whereas their expression was
      seen in 3.6% and 3.3% of nongastrointestinal tumors, respectively. CONCLUSION: We
      concluded that SATB2 and cadherin-17 were highly sensitive and specific markers
      for colorectal carcinomas and propose including MLH1, cadherin-17, and SATB2 in a
      routine immunostaining panel when working on a tumor of unknown primary,
      especially in an elderly patient with a CK7-/CK20- carcinoma.

PMID- 24437461
TI  - Clinical implications of irregular ADMET properties with levodopa and other
      antiparkinson's drugs.
AB  - INTRODUCTION: Parkinson's disease is a neurodegenerative disorder characterized
      by the loss of striatal dopaminergic neurons. Besides the improvement of the
      dopaminergic loss, the treatment focuses on non-dopaminergic medication targeting
      motor and non-motor symptoms, and on the development of neuroprotective
      medication. A good knowledge of the properties of the compounds used is essential
      not only for those involved in pharmacological research but also for those who
      treat Parkinson's disease patients, facing their still many unmet needs. AREAS
      COVERED: The review discusses the pharmacokinetic properties of levodopa (LD) and
      factors influencing them, the pharmacodynamics of LD and approaches with the aim
      of improving this, covering some of the other antiparkinson medications
      available. Among the non-dopaminergic agents, it focuses on research on
      kynurenines. A literature search was made in PubMed for Parkinson's disease
      treatment, LD, LD absorption, LD pharmacokinetics, continuous dopaminergic
      stimulation, LD-carbidopa intraintestinal gel therapy, dopamine agonists and
      monoamine oxidase-B inhibitors. EXPERT OPINION: Various factors can cause
      irregularities in the pharmacokinetics of LD, with interconnected consequences on
      its therapeutic effect. Its long-term use is associated with the development of
      motor complications; this is explained mostly by pharmacodynamic and also by
      pharmacokinetic properties, the latter gaining importance in the advanced stages
      of the disease.

PMID- 24437462
TI  - Crystal structure of Pedobacter heparinus heparin lyase Hep III with the active
      site in a deep cleft.
AB  - Pedobacter heparinus (formerly known as Flavobacterium heparinum) is a typical
      glycosaminoglycan-degrading bacterium that produces three heparin lyases, Hep I,
      Hep II, and Hep III, which act on heparins with 1,4-glycoside bonds between
      uronate and amino sugar residues. Being different from Hep I and Hep II, Hep III
      is specific for heparan sulfate. Here we describe the crystal structure of Hep
      III with the active site located in a deep cleft. The X-ray crystallographic
      structure of Hep III was determined at 2.20 A resolution using single-wavelength
      anomalous diffraction. This enzyme comprised an N-terminal alpha/alpha-barrel
      domain and a C-terminal antiparallel beta-sheet domain as its basic scaffold.
      Overall structures of Hep II and Hep III were similar, although Hep III exhibited
      an open form compared with the closed form of Hep II. Superimposition of Hep III
      and heparin tetrasaccharide-bound Hep II suggested that an active site of Hep III
      was located in the deep cleft at the interface between its two domains. Three
      mutants (N240A, Y294F, and H424A) with mutations at the active site had
      significantly reduced enzyme activity. This is the first report of the structure
      function relationship of P. heparinus Hep III. 

PMID- 24437463
TI  - Nanoskiving core-shell nanowires: a new fabrication method for nano-optics.
AB  - This paper describes the fabrication of functional optical devices by sectioning
      quantum-dot-in-nanowires systems with predefined lengths and orientations. This
      fabrication process requires only two steps, embedding the nanowires in epoxy and
      using an ultramicrotome to section them across their axis ("nanoskiving"). This
      work demonstrates the combination of the following four capabilities: (i) the
      control of the length of the nanowire sections at the nanometer scale; (ii) the
      ability to process the nanowires after cutting using wet etching; (iii) the
      possibility of modifying the geometry of the wire by varying the sectioning
      angle; and (iv) the generation of as many as 120 consecutive slabs bearing
      nanowires that have uniform size and approximately reproducible lateral patterns
      and that can subsequently be transferred to different substrates. The quantum
      dots inside the nanowires are functional and of a high optical quality after the
      sectioning process and exhibit photoluminescent emission with wavelengths in the
      range of 650-710 nm. 

PMID- 24437464
TI  - Highly coplanar very long oligo(alkylfuran)s: a conjugated system with specific
      head-to-head defect.
AB  - Well-defined monodisperse conjugated oligomers, which have planar backbones and
      are free from the disturbance of substituents, attract broad interest. Herein, we
      report a series of symmetrical, isomerically pure oligofurans, namely, the 16-mer
      16F-6C6 together with the related nF-2C6 (n = 4, 6, 8). Through computational
      studies and detailed spectroscopic and X-ray characterization, for the first
      time, we show that the planarity of the furan backbone is almost unaffected by
      the head-to-head defect which is known to cause considerable twists in its oligo-
      or polythiophene analogues. We present that the properties of these rigid
      oligo(alkylfuran)s are strongly influenced by the conjugation length. As the
      longest monodisperse alpha-oligofuran synthesized to date, 16F-6C6 was observed
      to be stable and highly fluorescent. Experimental and computational studies of
      the redox states of these oligo(alkylfuran)s reveal that 16F-6C6 has singlet
      biradical (polaron-pair) character in the doubly oxidized ground state: the open
      shell singlet (?S2? = 0.989) is 3.8 kcal/mol more stable than the closed-shell
      dication. 

PMID- 24437465
TI  - Construction and use of fragment-augmented molecular Hasse diagrams.
AB  - Collections of molecules can be organized in many different ways based on
      substructures that are common to two or more of the molecules. The article
      describes a method that builds on the ideas of partial orders and Hasse diagrams
      and which organizes molecules in a particularly simple and natural way using only
      sub- and superstructure relations. The method outputs the original molecule
      collection together with common substructures and a set of relations between
      fragments and molecules. The result is a complete deconstruction of the original
      structures into those fragments or building blocks that are shared between two or
      more molecules. Scaffolds for the R-group analyses that can be performed on the
      data set are automatically detected. Cyclic and linear substituents are treated
      in the same way. No rules are incorporated that express any form of domain
      expertise or judgment. The method should be useful for library profiling, data
      set navigation, fragment-based screening, identification of activity cliffs, and
      identification of library subsets that are amenable to fragment-based QSAR. 

PMID- 24437467
TI  - Single-component and binary CO2 and H2O adsorption of amine-functionalized
      cellulose.
AB  - A fundamental analysis of single-component and binary CO2 and H2O adsorption of
      amine-functionalized nanofibrillated cellulose is carried out in the temperature
      range of 283-353 K and at CO2 partial pressures in the range of 0.02-105 kPa,
      where the ultralow partial pressure range is relevant for the direct capture of
      CO2 from atmospheric air. Single-component CO2 and H2O adsorption experimental
      data are fitted to the Toth and Guggenheim-Anderson-de Boer models, respectively.
      Corresponding heats of adsorption, derived from explicit solutions of the van't
      Hoff equation, are -50 kJ/mol CO2 and -48.8 kJ/mol H2O. Binary CO2/H2O adsorption
      measurements for humid air reveal that the presence of H2O at 2.55 kPa enhances
      CO2 adsorption, while the presence of CO2 at 0.045 kPa does not influence H2O
      adsorption. The energy demand of the temperature-vacuum-swing
      adsorption/desorption cycle for delivering pure CO2 from air increases
      significantly with H2O adsorption and indicates the need to reduce the
      hygroscopicity of the adsorbent. 

PMID- 24437471
TI  - Syntheses of the fungal metabolites boletopsins 7, 11, and 12 from the Papua New
      Guinea medicinal mushroom Boletopsis sp.
AB  - Boletopsins 7 (1), 11 (2), and 12 (3) are p-terphenyl dibenzofuran compounds,
      isolated from the Papua New Guinean medicinal mushroom Boletopsis sp. The first
      syntheses of these fungal metabolites are reported, allowing for an investigation
      of their antibiotic activity. The key steps include sequential Suzuki-Miyaura
      couplings to rapidly form the p-terphenyl backbone and an Ullmann ether synthesis
      on a formate ester to create the dibenzofuran moiety. Biological evaluation of
      the synthetic compounds and intermediates against a panel of bacterial nosocomial
      pathogens was performed. 

PMID- 24437470
TI  - Detection and spatial mapping of mercury contamination in water samples using a
      smart-phone.
AB  - Detection of environmental contamination such as trace-level toxic heavy metal
      ions mostly relies on bulky and costly analytical instruments. However, a
      considerable global need exists for portable, rapid, specific, sensitive, and
      cost-effective detection techniques that can be used in resource-limited and
      field settings. Here we introduce a smart-phone-based hand-held platform that
      allows the quantification of mercury(II) ions in water samples with parts per
      billion (ppb) level of sensitivity. For this task, we created an integrated opto
      mechanical attachment to the built-in camera module of a smart-phone to digitally
      quantify mercury concentration using a plasmonic gold nanoparticle (Au NP) and
      aptamer based colorimetric transmission assay that is implemented in disposable
      test tubes. With this smart-phone attachment that weighs <40 g, we quantified
      mercury(II) ion concentration in water samples by using a two-color ratiometric
      method employing light-emitting diodes (LEDs) at 523 and 625 nm, where a custom
      developed smart application was utilized to process each acquired transmission
      image on the same phone to achieve a limit of detection of ~ 3.5 ppb. Using this
      smart-phone-based detection platform, we generated a mercury contamination map by
      measuring water samples at over 50 locations in California (USA), taken from city
      tap water sources, rivers, lakes, and beaches. With its cost-effective design,
      field-portability, and wireless data connectivity, this sensitive and specific
      heavy metal detection platform running on cellphones could be rather useful for
      distributed sensing, tracking, and sharing of water contamination information as
      a function of both space and time.

PMID- 24437472
TI  - Surfactant behavior of ionic liquids involving a drug: from molecular
      interactions to self-assembly.
AB  - Aggregates formed in an aqueous medium by three ionic liquids CnMImIbu made up of
      1-alkyl-3-methyl-imidazolium cation (n = 4, 6, 8) and ibuprofenate anion are
      investigated. Dynamic light scattering (DLS), cryogenic transmission electron
      microscopy (cryo-TEM), (1)H nuclear magnetic resonance measurements, and atom
      scale molecular dynamics simulations are used to shed light on the main
      interactions governing the formation of the aggregates and their composition. At
      high concentration, mixed micelles are formed with a composition that depends on
      the imidazolium alkyl chain length. For the shortest alkyl chain, micelles are
      mainly composed of ibuprofenate anions with some imidazolium cations intercalated
      between the anions. Upon increasing the alkyl chain length, the composition of
      the aggregates gets enriched in imidazolium cations and aggregates of
      stoichiometric composition are obtained. Attractive interactions between these
      aggregates led to the formation of larger aggregates. As suggested by molecular
      simulations, these larger aggregates might constitute the early stage of phase
      separation. Transitions from micelles to vesicles or ribbons are observed due to
      dilution effects and changes in the chemical composition of the aggregates. We
      also show that aggregation can be probed using simple microscopic quantities such
      as radial distribution functions and average solvation numbers. 

PMID- 24437474
TI  - Three-dimensional conformal coatings through the entrapment of polymer membrane
      precursors.
AB  - We report a technique to coat polymers onto 3D surfaces distinct from traditional
      spray, spin, or dip coating. In our technique, the surface of a template
      structure composed of poly(lactic acid) swells and entraps a soluble polymer
      precursor. Once entrapped, the precursor is cured, resulting in a thin, conformal
      membrane. The thickness of each coating depends on the coating solution
      composition, residence time, and template size. Thicknesses ranged from 400 nm to
      4 MUm within the experimental conditions we explored. The coating method was
      compatible with a range of polymers. Complicated 3D structures and
      microstructures of 10 MUm thickness and separation were coated using this
      technique. The templates can also be selectively removed, leaving behind a hollow
      membrane structure in the shape of the original printed, extruded, or microporous
      template structures. This technique may be useful in applications that benefit
      from three-dimensional membrane topologies, including catalysis, separations, and
      potentially tissue engineering. 

PMID- 24437477
TI  - Toward understanding induction of oxidative stress and apoptosis by proteasome
      inhibitors.
AB  - SIGNIFICANCE: Proteasome inhibitors (PIs) are used in the clinic for the
      treatment of hematopoietic malignancies. PI inhibitors induce endoplasmatic
      reticulum (ER) stress and oxidative stress, disruption of signaling pathways,
      mitochondrial dysfunction, and, eventually, cell death by apoptosis. PIs
      designated as clinical candidates include natural product derivatives and
      compounds developed by rational design and feature a wide diversity of structural
      elements. The vast amount of literature on this topic underscores PIs
      significance in driving basic research alongside therapeutic benefit. RECENT
      ADVANCES: Research in recent years has brought an in-depth insight into the
      molecular mechanisms of PI-induced apoptosis. However, there are some paradoxes
      and controversies in the literature. In this review, the advances and
      uncertainties, in particular on the time course events that make cells commit to
      apoptosis, are discussed. In addition, some mechanisms of evolved PI resistance
      are presented, and speculations on the difference in sensitivity between cell or
      tumor types are brought forward. The review concludes by giving an outlook of
      recent methods that may be employed to describe the system biology of how PIs
      impact cell survival decisions. CRITICAL ISSUES: The biology of ER stress,
      reactive oxygen species (ROS) production, and apoptosis as induced by PIs is not
      well understood. Absorbed by the strong focus on PIs, one might overlook the
      importance of proteasome activity activators or modulators and the study of
      enzymatic pathways that lie up- or downstream from the proteasome function.
      FUTURE DIRECTIONS: An increased understanding of the systems biology at mRNA and
      protein levels and the kinetics behind the interaction between PIs and cells is
      imperative. The design and synthesis of subunit specific inhibitors for each of
      the seven known proteasome activities and for the enzymes associated to
      proteasomes will aid in unraveling biology of the ubiquitin-proteasome system in
      relation to ER stress, ROS production, and apoptosis and will generate leads for
      therapeutic intervention.

PMID- 24437480
TI  - Solvothermal preparation of an electrocatalytic metalloporphyrin MOF thin film
      and its redox hopping charge-transfer mechanism.
AB  - A thin film of a metalloporphyrin metal-organic framework consisting of
      [5,10,15,20-(4-carboxyphenyl)porphyrin]Co(III) (CoTCPP) struts bound by linear
      trinuclear Co(II)-carboxylate clusters has been prepared solvothermally on
      conductive fluorine-doped tin oxide substrates. Characterization of this
      mesoporous thin film material, designated as CoPIZA/FTO, which is equipped with
      large cavities and access to metal active sites, reveals an electrochemically
      active material. Cyclic voltammetry displays a reversible peak with E(1/2) at 
      1.04 V vs ferrocyanide attributed to the (Co(III/II)TCPP)CoPIZA redox couple and
      a quasi-reversible peak at -1.45 V vs ferrocyanide, which corresponds to the
      reduction of (Co(II/I)TCPP)CoPIZA. Analysis of the spectroelectrochemical
      response for the (Co(II/I)TCPP)CoPIZA redox couple revealed non-Nernstian
      reduction with a nonideality factor of 2 and an E(1/2) of -1.39 V vs
      ferrocyanide. The film was shown to retain its structural integrity with applied
      potential, as was demonstrated spectroelectrochemically with maintenance of
      isosbestic points at 430, 458, and 544 nm corresponding to the
      (Co(III/II)TCPP)CoPIZA transition and at 390 and 449 nm corresponding to the
      (Co(II/I)TCPP)CoPIZA transition. The mechanism of charge transport through the
      film is proposed to be a redox hopping mechanism, which is supported by both
      cyclic voltammetry and spectroelectrochemistry. A fit of the time-dependent
      spectroelectrochemical data to a modified Cottrell equation gave an apparent
      diffusion coefficient of 7.55 (+/-0.05) * 10(-14) cm(2)/s for ambipolar electron
      and cation transport throughout the film. Upon reduction of the metalloporphyrin
      struts to (Co(I)TCPP)CoPIZA, the CoPIZA thin film demonstrated catalytic activity
      for the reduction of carbon tetrachloride.

PMID- 24437481
TI  - Synthesis and supramolecular assembly of pentacyclic dithienofluorene and
      diselenophenofluorene derivatives.
AB  - 2,7-Diiodo-3,6-dibromofluorene and 2,7-dichloro-3,6-dibromofluorene have been
      successfully synthesized. The two key intermediates enable us to implement a
      regioselective Sonogashira reaction followed by intramolecular thiolate/acetylene
      cyclization, forming two regiospecific pentacyclic dithieno[2,3-b:7,6-b']fluorene
      (2,7-DTF) and dithieno[3,2-b:6,7-b']fluorene (3,6-DTF) isomeric molecules,
      respectively. By using a similar strategy, selenophene-based diselenopheno[2,3
      b:7,6-b']fluorene (2,7-DSF) as well as diselenopheno[3,2-b:6,7-b']fluorene (3,6
      DSF) were also prepared. The isomeric and sulfur/selenium effects determine the
      optical, electrochemical, and orbital properties. X-ray crystallography revealed
      that 2,7-DTF and 3,6-DTF molecules assemble into supramolecular helical
      structures. 

PMID- 24437485
TI  - FoxO1 is a negative regulator of FSHbeta gene expression in basal and GnRH
      stimulated conditions in female.
AB  - The importance of forkhead box class O (FoxO) proteins in reproductive
      endocrinology has been confirmed by age-dependent infertility in females in a
      FoxO3a-knockout mouse model. In this study, FoxO1 was detected in gonadotropes in
      the anterior pituitary. Overexpression of FoxO1 in primary pituitary cells
      decreased FSHbeta gene expression in both basal and GnRH-stimulated conditions,
      and this result was replicated by the human FSHbeta promoter activity. Although
      direct binding of FoxO1 to FoxO-binding element (FBE) (at -124 to -119 bp of the
      human FSHbeta promoter) was not detected in an electrophoretic mobility shift
      assay, a DNA pull-down assay and transfection study using the mutant FBE reporter
      vector revealed that FBE is necessary in FSHbeta suppression by FoxO1, suggestive
      of other cofactor requirements. GnRH stimulated the phosphoinositide 3-kinase
      pathway, which induced posttranslational modification of FoxO1 and retained it in
      the cytoplasm. We also confirmed this result in primary cell cultures; most of
      the FoxO1 was detected in the cytoplasm when treated with GnRH but in the nucleus
      when the phosphoinositide 3-kinase pathway was inhibited. These findings suggest
      that FoxO1 is regulated by the GnRH signaling pathway and functions as a negative
      regulator of FSHbeta gene expression. 

PMID- 24437486
TI  - Activation of hepatic inflammatory pathways by catecholamines is associated with
      hepatic insulin resistance in male ischemic stroke rats.
AB  - Patients who experience acute ischemic stroke may develop hyperglycemia, even in
      the absence of diabetes. In the current study we determined the effects of acute
      stroke on hepatic insulin signaling, TNF-alpha expression, endoplasmic reticulum
      (ER) stress, the activities of c-Jun N-terminal kinase (JNK), inhibitor kappaB
      kinase beta (IKK-beta), and nuclear factor-kappaB (NF-kappaB) pathways. Rats with
      cerebral ischemia developed higher blood glucose, and insulin levels, and insulin
      resistance index, as well as hepatic gluconeogenic enzyme expression compared
      with the sham-treated group. The hepatic TNF-alpha mRNA and protein levels were
      elevated in stroke rats in association with increased ER stress, phosphorylation
      of JNK1/2 and IKK-beta proteins, IkappaB/NF-kappaB signaling, and phosphorylation
      of insulin receptor-1 (IRS-1) at serine residue. The basal and insulin-stimulated
      tyrosine phosphorylation of IRS-1 and AKT proteins was reduced. In addition,
      acute stroke increased circulating catecholamines in association with hepatic
      adrenergic signaling activation. After administration of a nonselective beta
      adrenergic receptor blocker (propranolol) before induction of cerebral ischemic
      injury, hepatic adrenergic transduction, TNF-alpha expression, ER stress, and the
      activation of the JNK1/2, IKK-beta, and NF-kappaB pathways, and serine
      phosphorylation of IRS-1 were all attenuated. In contrast, the phosphorylated IRS
      1 at tyrosine site and AKT levels were partially restored with improved
      poststroke hyperglycemia and insulin resistance index. These results suggest that
      acute ischemic stroke can activate proinflammatory pathways in the liver by the
      catecholamines and is associated with the development of hepatic insulin
      resistance. 

PMID- 24437487
TI  - Liver mTOR controls IGF-I bioavailability by regulation of protein kinase CK2 and
      IGFBP-1 phosphorylation in fetal growth restriction.
AB  - Fetal growth restriction (FGR) increases the risk for perinatal complications and
      predisposes the infant to diabetes and cardiovascular disease later in life. No
      treatment for FGR is available, and the underlying pathophysiology remains poorly
      understood. Increased IGFBP-1 phosphorylation has been implicated as an important
      mechanism by which fetal growth is reduced. However, to what extent circulating
      IGFBP-1 is phosphorylated in FGR is unknown, and the molecular mechanisms linking
      FGR to IGFBP-1 phosphorylation have not been established. We used umbilical cord
      plasma of appropriate for gestational age (AGA) and growth-restricted human
      fetuses and determined IGFBP-1 and IGF-I concentrations (ELISA) and site-specific
      IGFBP-1 phosphorylation (Western blotting using IGFBP-1 phospho-site specific
      antibodies). In addition, we used a baboon model of FGR produced by 30% maternal
      nutrient restriction and determined mammalian target of rapamycin (mTOR)C1
      activity, CK2 expression/activity, IGFBP-1 expression and phosphorylation, and
      IGF-I levels in baboon fetal liver by Western blot, enzymatic assay, and ELISA.
      HepG2 cells and primary fetal baboon hepatocytes were used to explore mechanistic
      links between mTORC1 signaling and IGFBP-1 phosphorylation. IGFBP-1 was
      hyperphosphorylated at Ser101, Ser119, and Ser169 in umbilical plasma of human
      FGR fetuses. IGFBP-1 was also hyperphosphorylated at Ser101, Ser119, and Ser169
      in the liver of growth-restricted baboon fetus. mTOR signaling was markedly
      inhibited, whereas expression and activity of CK2 was increased in growth
      restricted baboon fetal liver in vivo. Using HepG2 cells and primary fetal baboon
      hepatocytes, we established a mechanistic link between mTOR inhibition, CK2
      activation, IGFBP-1 hyperphosphorylation, and decreased IGF-I-induced IGF-I
      receptor autophosphorylation. We provide clear evidence for IGFBP-1
      hyperphosphorylation in FGR and identified an mTOR and CK2-mediated mechanism for
      regulation of IGF-I bioavailability. Our findings are consistent with the model
      that inhibition of mTOR in the fetal liver, resulting in increased CK2 activity
      and IGFBP-1 hyperphosphorylation, constitutes a novel mechanistic link between
      nutrient deprivation and restricted fetal growth. 

PMID- 24437488
TI  - Epithelial and stromal cells of bovine endometrium have roles in innate immunity
      and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll
      like receptors TLR2, TLR1, and TLR6.
AB  - Bacteria often infect the endometrium of cattle to cause endometritis, uterine
      disease, and infertility. Lipopeptides are commonly found among bacteria and are
      detected by the Toll-like receptor (TLR) cell surface receptor TLR2 on immune
      cells. Heterodimers of TLR2 with TLR1 or TLR6 activate MAPK and nuclear factor
      kappaB intracellular signaling pathways to stimulate inflammatory responses. In
      the endometrium, epithelial and stromal cells are the first to encounter invading
      bacteria, so the present study explored whether endometrial cells can also mount
      inflammatory responses to bacterial lipopeptides via TLRs. The supernatants of
      pure populations of primary bovine endometrial epithelial and stromal cells
      accumulated the cytokine IL-6 and the chemokine IL-8 in response to triacylated
      or diacylated bacterial lipopeptides. The accumulation of IL-6 and IL-8 in
      response to triacylated lipopeptides was reduced by small interfering RNA
      targeting TLR2 or TLR1 but not TLR6, whereas cellular responses to diacylated
      lipopeptide were reduced by small interfering RNA targeting TLR2, TLR1, or TLR6.
      Both lipopeptides induced rapid phosphorylation of ERK1/2, p38, and nuclear
      factor-kappaB in endometrial cells, and inhibitors of ERK1/2 or p38 limited the
      accumulation of IL-6. The ovarian steroids estradiol and progesterone had little
      impact on inflammatory responses to lipopeptides. The endometrial epithelial and
      stromal cell responses to lipopeptides via TLR2, TLR1, and TLR6 provide a
      mechanism linking a wide range of bacterial infections to inflammation of the
      endometrium. 

PMID- 24437489
TI  - FoxO6 integrates insulin signaling with MTP for regulating VLDL production in the
      liver.
AB  - Excessive production of triglyceride-rich very low-density lipoproteins (VLDL-TG)
      contributes to hypertriglyceridemia in obesity and type 2 diabetes. To understand
      the underlying mechanism, we studied hepatic regulation of VLDL-TG production by
      (forkhead box O6) FoxO6, a forkhead transcription factor that integrates insulin
      signaling to hepatic metabolism. We showed that transgenic mice expressing a
      constitutively active FoxO6 allele developed hypertriglyceridemia, culminating in
      elevated VLDL-TG levels and impaired postprandial TG clearance. This effect
      resulted in part from increased hepatic VLDL-TG production. We recapitulated
      these findings in cultured HepG2 cells and human primary hepatocytes,
      demonstrating that FoxO6 promoted hepatic VLDL-TG secretion. This action
      correlated with the ability of FoxO6 to stimulate hepatic production of
      microsomal triglyceride transfer protein (MTP), a molecular chaperone that
      catalyzes the rate-limiting step in VLDL-TG assembly and secretion. FoxO6 was
      shown to bind to the MTP promoter and stimulate MTP promoter activity in HepG2
      cells. This effect was inhibited by insulin, consistent with the ability of
      insulin to promote FoxO6 phosphorylation and disable FoxO6 DNA-binding activity.
      Mutations of the FoxO6 target site within the MTP promoter abrogated FoxO6
      mediated induction of MTP promoter activity. Hepatic FoxO6 expression became
      deregulated in insulin-resistant mice with obesity and type 2 diabetes. FoxO6
      inhibition in insulin-resistant liver suppressed hepatic MTP expression and
      curbed VLDL-TG overproduction, contributing to the amelioration of
      hypertriglyceridemia in obese and diabetic db/db mice. These results characterize
      FoxO6 as an important signaling molecule upstream of MTP for regulating hepatic
      VLDL-TG production. 

PMID- 24437491
TI  - Transdifferentiation of differentiated ovary into functional testis by long-term
      treatment of aromatase inhibitor in Nile tilapia.
AB  - Females with differentiated ovary of a gonochoristic fish, Nile tilapia, were
      masculinized by long-term treatment with an aromatase inhibitor (Fadrozole) in
      the present study. The reversed gonads developed into functional testes with
      fertile sperm. The longer the fish experienced sex differentiation, the longer
      treatment time was needed for successful sex reversal. Furthermore, Fadrozole
      induced sex reversal, designated as secondary sex reversal (SSR), was
      successfully rescued by supplement of exogenous 17beta-estradiol. Gonadal
      histology, immunohistochemistry, transcriptome, and serum steroid level were
      analyzed during SSR. The results indicated that spermatogonia were transformed
      from oogonia or germline stem cell-like cells distributed in germinal epithelium,
      whereas Leydig and Sertoli cells probably came from the interstitial cells and
      granulosa cells of the ovarian tissue, respectively. The transdifferentiation of
      somatic cells, as indicated by the appearance of doublesex- and Mab-3-related
      transcription factor 1 (pre-Sertoli cells) and cytochrome P450, family 11,
      subfamily B, polypeptide 2 (pre-Leydig cells)-positive cells in the ovary,
      provided microniche for the transdifferentiation of germ cells. Decrease of serum
      17beta-estradiol was detected earlier than increase of serum 11-ketotestosterone,
      indicating that decrease of estrogen was the cause, whereas increase of androgen
      was the consequence of SSR. The sex-reversed gonad displayed more similarity in
      morphology and histology with a testis, whereas the global gene expression
      profiles remained closer to the female control. Detailed analysis indicated that
      transdifferentiation was driven by suppression of female pathway genes and
      activation of male pathway genes. In short, SSR provides a good model for study
      of sex reversal in teleosts and for understanding of sex determination and
      differentiation in nonmammalian vertebrates. 

PMID- 24437490
TI  - Metformin inhibits androgen-induced IGF-IR up-regulation in prostate cancer cells
      by disrupting membrane-initiated androgen signaling.
AB  - We have previously demonstrated that, in prostate cancer cells, androgens up
      regulate IGF-I receptor (IGF-IR) by inducing cAMP-response element-binding
      protein (CREB) activation and CREB-dependent IGF-IR gene transcription through
      androgen receptor (AR)-dependent membrane-initiated effects. This IGF-IR up
      regulation is not blocked by classical antiandrogens and sensitizes cells to IGF
      I-induced biological effects. Metformin exerts complex antitumoral functions in
      various models and may inhibit CREB activation in hepatocytes. We, therefore,
      evaluated whether metformin may affect androgen-dependent IGF-IR up-regulation.
      In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits
      androgen-induced CRE activity and IGF-IR gene transcription. CRE activity
      requires the formation of a CREB-CREB binding protein-CREB regulated
      transcription coactivator 2 (CRTC2) complex, which follows Ser133-CREB
      phosphorylation. Metformin inhibited Ser133-CREB phosphorylation and induced
      nuclear exclusion of CREB cofactor CRTC2, thus dissociating the CREB-CREB binding
      protein-CRTC2 complex and blocking its transcriptional activity. Similarly to
      metformin action, CRTC2 silencing inhibited IGF-IR promoter activity. Moreover,
      metformin blocked membrane-initiated signals of AR to the mammalian target of
      rapamycin/p70S6Kinase pathway by inhibiting AR phosphorylation and its
      association with c-Src. AMPK signals were also involved to some extent. By
      inhibiting androgen-dependent IGF-IR up-regulation, metformin reduced IGF-I
      mediated proliferation of LNCaP cells. These results indicate that, in prostate
      cancer cells, metformin inhibits IGF-I-mediated biological effects by disrupting
      membrane-initiated AR action responsible for IGF-IR up-regulation and suggest
      that metformin could represent a useful adjunct to the classical antiandrogen
      therapy. 

PMID- 24437492
TI  - Bioenergetics during calvarial osteoblast differentiation reflect strain
      differences in bone mass.
AB  - Osteoblastogenesis is the process by which mesenchymal stem cells differentiate
      into osteoblasts that synthesize collagen and mineralize matrix. The pace and
      magnitude of this process are determined by multiple genetic and environmental
      factors. Two inbred strains of mice, C3H/HeJ and C57BL/6J, exhibit differences in
      peak bone mass and bone formation. Although all the heritable factors that differ
      between these strains have not been elucidated, a recent F1 hybrid expression
      panel (C3H * B6) revealed major genotypic differences in osteoblastic genes
      related to cellular respiration and oxidative phosphorylation. Thus, we
      hypothesized that the metabolic rate of energy utilization by osteoblasts
      differed by strain and would ultimately contribute to differences in bone
      formation. In order to study the bioenergetic profile of osteoblasts, we measured
      oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) first
      in a preosteoblastic cell line MC3T3-E1C4 and subsequently in primary calvarial
      osteoblasts from C3H and B6 mice at days 7, 14, and 21 of differentiation. During
      osteoblast differentiation in media containing ascorbic acid and beta
      glycerophosphate, all 3 cell types increased their oxygen consumption and
      extracellular acidification rates compared with the same cells grown in regular
      media. These increases are sustained throughout differentiation. Importantly, C3H
      calvarial osteoblasts had greater oxygen consumption rates than B6 consistent
      with their in vivo phenotype of higher bone formation. Interestingly, osteoblasts
      utilized both oxidative phosphorylation and glycolysis during the differentiation
      process although mature osteoblasts were more dependent on glycolysis at the 21
      day time point than oxidative phosphorylation. Thus, determinants of oxygen
      consumption reflect strain differences in bone mass and provide the first
      evidence that during collagen synthesis osteoblasts use both glycolysis and
      oxidative phosphorylation to synthesize and mineralize matrix. 

PMID- 24437494
TI  - Predicting the failure of a thin liquid film loaded with spherical particles.
AB  - A model is presented for predicting the failure of a thin liquid film stabilized
      by attached inert particles. A statistical analysis of roughly 3500 Surface
      Evolver1 simulations was used to identify the relationship between the packing
      density of the particles on the film, their contact angle distribution, and the
      capillary pressure required to rupture the film. The model presented allows a
      fast and simple method of calculating the range of pressures a thin film in a
      three-phase froth will fail at based upon three variables: the film loading, mean
      particle contact angle, and the standard distribution of contact angles round the
      mean. The predicted range of failure pressures can be used in simulations of bulk
      froth properties where bubble coalescence is an important factor governing the
      froth properties. 

PMID- 24437495
TI  - Charge separation pathways in a highly efficient polymer: fullerene solar cell
      material.
AB  - PBDTTPD is one of the best conjugated polymers for solar cell applications (up to
      8.5% efficiency). We have investigated the dynamics of charge generation in the
      blend with fullerene (PCBM) and addressed highly relevant topics such as the role
      of bulk heterojunction structure, fullerene excitation, and excess energy. We
      show that there are multiple charge separation pathways. These include electron
      transfer from photoexcited polymer, hole transfer from photoexcited PCBM, prompt
      (<100 fs) charge generation in intimately mixed polymer:fullerene regions (which
      can occur from hot states), as well as slower electron and hole transfer from
      excitons formed in pure PBDTTPD or PCBM domains (diffusion to an interface is
      necessary). Very interestingly, all the charge separation pathways are highly
      efficient. For example, the yield of long-lived carriers is not significantly
      affected by the excitation wavelength, although this changes the fraction of
      photons absorbed by PCBM and the amount of excess energy brought to the system.
      Overall, the favorable properties of the PBDTTPD:PCBM blend in terms of
      morphology and exciton delocalization allow excellent charge generation in all
      circumstances and strongly contribute to the high photovoltaic performance of the
      blend. 

PMID- 24437500
TI  - Electrodeposition of antimony selenide thin films and application in
      semiconductor sensitized solar cells.
AB  - Sb2Se3 thin films are proposed as an alternative light harvester for
      semiconductor sensitized solar cells. An innovative electrodeposition route,
      based on aqueous alkaline electrolytes, is presented to obtain amorphous Sb2Se3.
      The amorphous to crystalline phase transition takes place during a soft thermal
      annealing in Ar atmosphere. The potential of the Sb2Se3 electrodeposited thin
      films in semiconductor sensitized solar cells is evaluated by preparing
      TiO2/Sb2Se3/CuSCN planar heterojunction solar cells. The resulting devices
      generate electricity from the visible and NIR photons, exhibiting the external
      quantum efficiency onset close to 1050 nm. Although planar architecture is not
      optimized in terms of charge carrier collection, photocurrent as high as 18
      mA/cm(2), under simulated (AM1.5G) solar light, is achieved. Furthermore, the
      effect of the Sb2Se3 thickness and microstructural properties on the photocurrent
      is analyzed, suggesting the hole transport is the main limiting mechanism. The
      present findings provide significant insights to design efficient semiconductor
      sensitized solar cells based on advanced architectures (e.g., nanostructured and
      tandem), opening wide possibilities for progresses in this emerging photovoltaics
      technology. 

PMID- 24437493
TI  - Effects of cavities at the nicotinamide binding site of liver alcohol
      dehydrogenase on structure, dynamics and catalysis.
AB  - A role for protein dynamics in enzymatic catalysis of hydrogen transfer has
      received substantial scientific support, but the connections between protein
      structure and catalysis remain to be established. Valine residues 203 and 207 are
      at the binding site for the nicotinamide ring of the coenzyme in liver alcohol
      dehydrogenase and have been suggested to facilitate catalysis with "protein
      promoting vibrations" (PPV). We find that the V207A substitution has small
      effects on steady-state kinetic constants and the rate of hydrogen transfer; the
      introduced cavity is empty and is tolerated with minimal effects on structure
      (determined at 1.2 A for the complex with NAD(+) and 2,3,4,5,6-pentafluorobenzyl
      alcohol). Thus, no evidence is found to support a role for Val-207 in the
      dynamics of catalysis. The protein structures and ligand geometries (including
      donor-acceptor distances) in the V203A enzyme complexed with NAD(+) and 2,3,4,5,6
      pentafluorobenzyl alcohol or 2,2,2-trifluoroethanol (determined at 1.1 A) are
      very similar to those for the wild-type enzyme, except that the introduced cavity
      accommodates a new water molecule that contacts the nicotinamide ring. The
      structures of the V203A enzyme complexes suggest, in contrast to previous
      studies, that the diminished tunneling and decreased rate of hydride transfer (16
      fold, relative to that of the wild-type enzyme) are not due to differences in
      ground-state ligand geometries. The V203A substitution may alter the PPV and the
      reorganization energy for hydrogen transfer, but the protein scaffold and
      equilibrium thermal motions within the Michaelis complex may be more significant
      for enzyme catalysis. 

PMID- 24437501
TI  - Impacts of beach wrack removal via grooming on surf zone water quality.
AB  - Fecal indicator bacteria (FIB) are used to assess the microbial water quality of
      recreational waters. Increasingly, nonfecal sources of FIB have been implicated
      as causes of poor microbial water quality in the coastal environment. These
      sources are challenging to quantify and difficult to remediate. The present study
      investigates one nonfecal FIB source, beach wrack (decaying aquatic plants), and
      its impacts on water quality along the Central California coast. The prevalence
      of FIB on wrack was studied using a multibeach survey, collecting wrack
      throughout Central California. The impacts of beach grooming, to remove wrack,
      were investigated at Cowell Beach in Santa Cruz, California using a long-term
      survey (two summers, one with and one without grooming) and a 48 h survey during
      the first ever intensive grooming event. FIB were prevalent on wrack but highly
      variable spatially and temporally along the nine beaches sampled in Central
      California. Beach grooming was generally associated with either no change or a
      slight increase in coastal FIB concentrations and increases in surf zone
      turbidity and silicate, phosphate, and dissolved inorganic nitrogen
      concentrations. The findings suggest that beach grooming for wrack removal is not
      justified as a microbial pollution remediation strategy. 

PMID- 24437504
TI  - Regulation of the proteasome: evaluating the lung proteasome as a new therapeutic
      target.
AB  - SIGNIFICANCE: Lung diseases are on the second rank worldwide with respect to
      morbidity and mortality. For most respiratory diseases, no effective therapies
      exist. Whereas the proteasome has been successfully evaluated as a novel target
      for therapeutic interventions in cancer, neurodegenerative, and cardiac
      disorders, there is a profound lack of knowledge on the regulation of proteasome
      activity in chronic and acute lung diseases. RECENT ADVANCES: There are various
      means of how the amount of active proteasome complexes in the cell can be
      regulated such as transcriptional regulation of proteasomal subunit expression,
      association with different regulators, assembly and half-life of proteasomes and
      regulatory complexes, as well as post-translational modifications. It also
      becomes increasingly evident that proteasome activity is fine-tuned and depends
      on the state of the cell. We propose here that 20S proteasomes and their
      regulators can be regarded as dynamic building blocks, which assemble or
      disassemble in response to cellular needs. The composition of proteasome
      complexes in a cell may vary depending on tissue, cell type and compartment,
      stage of development, or pathological context. CRITICAL ISSUES AND FUTURE
      DIRECTIONS: Dissecting the expression and regulation of the various catalytic
      forms of 20S proteasomes, such as constitutive, immuno-, and mixed proteasomes,
      together with their associated regulatory complexes will not only greatly enhance
      our understanding of proteasome function in lung pathogenesis but will also pave
      the way to develop new classes of drugs that inhibit or activate proteasome
      function in a defined setting for treatment of lung diseases.

PMID- 24437505
TI  - Molecular dynamics studies of the protein-protein interactions in inhibitor of
      kappaB kinase-beta.
AB  - Activation of the inhibitor of kappaB kinase subunit beta (IKKbeta) oligomer
      initiates a cascade that results in the translocation of transcription factors
      involved in mediating immune responses. Dimerization of IKKbeta is required for
      its activation. Coarse-grained and atomistic molecular dynamics simulations were
      used to investigate the conformation-activity and structure-activity
      relationships within the oligomer assembly of IKKbeta that are impacted upon
      activation, mutation, and binding of ATP. Intermolecular interactions, free
      energies, and conformational changes were compared among several conformations,
      including a monomer, two different dimers, and the tetramer. Modifications to the
      activation segment induce conformational changes that disrupt dimerization and
      suggest that the multimeric assembly mediates a global stability for the enzyme
      that influences the activity of IKKbeta. 

PMID- 24437506
TI  - Aminative umpolung of aldehydes to alpha-amino anion equivalents for Pd-catalyzed
      allylation: an efficient synthesis of homoallylic amines.
AB  - An attractive strategy for generation of alpha-amino anions from aldehydes with
      applications in synthesis of homoallylic amines is described. Aromatic aldehydes
      can be converted to alpha-amino anion equivalents via amination with 2,2
      diphenylglycine and subsequent decarboxylation. The in situ generated alpha-imino
      anions are highly reactive for Pd-catalyzed allylation, forming the corresponding
      homoallylic amines in high yields with excellent regioselectivity. 

PMID- 24437507
TI  - Titanium nitride-nickel nanocomposite as heterogeneous catalyst for the
      hydrogenolysis of aryl ethers.
AB  - Lignin from biomass can become a sustainable source of aromatic compounds. Its
      depolymerization can be accomplished through hydrogenolysis, although the
      development of catalysts based on cheap and abundant metals is lacking. Herein, a
      sustainable composite based on titanium nitride and nickel is synthesized and
      employed as catalyst for the hydrogenolysis of aryl ethers as models for lignin.
      The catalytic activity of the new material during hydrogenation reactions is
      proven to be superior to that of either component alone. In particular, different
      aryl ethers could be efficiently converted under relatively mild conditions into
      aromatic compounds and cycloalkanes within minutes. 

PMID- 24437510
TI  - Practical and intuitive surgical approach renal ranking to predict outcomes in
      the management of renal tumors: a novel score tool.
AB  - BACKGROUND AND PURPOSE: Surgery continues to be the main form of treatment for
      patients with renal tumors. We create a more practical and intuitive score for
      renal tumor classification. PATIENTS AND METHODS: Eighty patients underwent
      surgery for renal tumors and were prospectively enrolled. The tumors were
      classified using the following variables: (1) tumor size, (2) endophytic or
      exophytic tumor, (3) longitudinal location of the tumor, (4) the extent of the
      impairment of the renal parenchyma, (5) relationship with the renal sinus, and
      (6) anterior or posterior. RESULTS: The mean operative time, tumor size,and
      bleeding increased proportionally to the increased complexity of the tumor
      measured by scores (P<0.0001, P<0.0001, and P=0.036, respectively). The mean
      total score was 8.7 points for patients undergoing partial nephrectomy (PN) and
      14.4 points for those undergoing radical nephrectomy (RN) (P<0.0001). Patients
      with larger tumors, completely endophytic, which exceeded the renal medulla, and
      were centrally located, underwent RN more often (86.7% - P<0.0001, 64% - P=0.01,
      77% - P<0.0001, and 78.9% - P<0.0001, respectively). In univariate analysis, RN
      was associated with tumors larger than 7 cm (P=0.001), tumors that exceeded the
      renal medullary (<0.001), centrally located tumors (odds ration [OR]=150,
      P<0.001), and tumors of high complexity (P<0.001). Analysis showed no association
      between complications and variables in the score. The findings were similar when
      the tumors were evaluated with the R.E.N.A.L. score system. CONCLUSION: Surgical
      Approach Renal Ranking is a simple, practical and intuitive classification for
      renal tumors that can be used in the decision-making process and to predict
      outcomes in the surgical treatment of patients with renal tumors.

PMID- 24437511
TI  - Self-assembly of collagen on flat surfaces: the interplay of collagen-collagen
      and collagen-substrate interactions.
AB  - Fibrillar collagens, common tissue scaffolds in live organisms, can also self
      assemble in vitro from solution. While previous in vitro studies showed that the
      pH and the electrolyte concentration in solution largely control the collagen
      assembly, the physical reasons why such control could be exerted are still
      elusive. To address this issue and to be able to simulate self-assembly over
      large spatial and temporal scales, we have developed a microscopic model of
      collagen with explicit interactions between the units that make up the collagen
      molecules, as well as between these units and the substrate. We have used this
      model to investigate assemblies obtained via molecular dynamics deposition of
      collagen on a substrate at room temperature using an implicit solvent. By
      comparing the morphologies from our molecular dynamics simulations with those
      from our atomic-force microscopy experiments, we have found that the assembly is
      governed by the competition between the collagen-collagen interactions and those
      between collagen and the substrate. The microscopic model developed here can
      serve for guiding future experiments that would explore new regions of the
      parameter space. 

PMID- 24437513
TI  - Controlled synthesis and catalytic activity of copper sulfide nanostructured
      assemblies with different morphologies.
AB  - A simple, template-free and mild solution chemistry route was employed to
      synthesize diverse copper sulfide (CuS) nanostructured assemblies at 70  degrees
      C by varying the solvent (water or ethylene glycol, or their ratios (3:1, 1:1 and
      1:3)). The CuS structures in the shape of spheres and nanotubes were found to be
      assemblies of either nanoplates or nanoparticles. The nanotube formation was
      elaborately studied by varying the synthesis parameters such as temperature,
      reaction duration, precursor's ratio, and counterions. Counterions such as NO3(-)
      and SO4(2-) were found to be suitable for nanotube formation whereas in the
      presence of Cl(-) and OAc(-) ions, CuS flake-like and nanoparticle assemblies are
      obtained, respectively. The optical bandgaps for the CuS with different
      morphologies were measured to be in the range of 1.88-2.16 eV. The bandgap of CuS
      in the visible region of electromagnetic radiation prompted it to be used as
      photocatalyst in the past under natural light. However, we demonstrate here the
      similar catalytic performance of as-synthesized CuS nanostructures for the
      degradation of methylene blue in the dark, suggesting that light does not play a
      role in its catalytic behavior. 

PMID- 24437518
TI  - The ubiquitin-proteasome system in neurodegeneration.
AB  - SIGNIFICANCE: Impairment of the ubiquitin-proteasome system (UPS) has been
      implicated in the pathogenesis of a wide variety of neurodegenerative disorders,
      including Alzheimer's, Parkinson's, and Huntington's diseases. The most
      significant risk factor for the development of these disorders is aging, which is
      associated with a progressive decline in UPS activity and the accumulation of
      oxidatively modified proteins. To date, no therapies have been developed that can
      specifically up-regulate this system. RECENT ADVANCES: In the neurodegenerative
      brain, dysfunction of the UPS has been associated with the deposition of
      ubiquitinated protein aggregates and widespread disruption of the proteostasis
      network. Recent research has identified further evidence of impairment in
      substrate ubiquitination and proteasomal degradation, which could contribute to
      the loss of cellular proteostasis in neurodegenerative disease. Novel strategies
      for activation of the UPS by genetic manipulation and treatment with synthetic
      compounds have also recently been identified. CRITICAL ISSUES: Here, we discuss
      the specific roles of the UPS in the healthy central nervous system and establish
      how dysfunctional components can contribute to neurotoxicity in the context of
      disease. FUTURE DIRECTIONS: Knowledge of the UPS components that are specifically
      or preferentially involved in neurodegenerative disease will be critical in the
      development of targeted therapies which aim at limiting the accumulation of
      misfolded proteins without gross disturbance of this major proteolytic pathway.

PMID- 24437519
TI  - Titania-promoted carboxylic acid alkylations of alkenes and cascade addition
      cyclizations.
AB  - Photochemical reactions employing TiO2 and carboxylic acids under dry anaerobic
      conditions led to several types of C-C bond-forming processes with electron
      deficient alkenes. The efficiency of alkylation varied appreciably with
      substituents in the carboxylic acids. The reactions of aryloxyacetic acids with
      maleimides resulted in a cascade process in which a pyrrolochromene derivative
      accompanied the alkylated succinimide. The selectivity for one or other of these
      products could be tuned to some extent by employing the photoredox catalyst under
      different conditions. Aryloxyacetic acids adapted for intramolecular ring
      closures by inclusion of 2-alkenyl, 2-aryl, or 2-oximinyl functionality reacted
      rather poorly. Profiles of reactant consumption and product formation for these
      systems were obtained by an in situ NMR monitoring technique. An array of
      different catalyst forms were tested for efficiency and ease of use. The proposed
      mechanism, involving hole capture at the TiO2 surface by the carboxylates
      followed by CO2 loss, was supported by EPR spectroscopic evidence of the
      intermediates. Deuterium labeling indicated that the titania likely donates
      protons from surface hydroxyl groups as well as supplying electrons and holes,
      thus acting as both a catalyst and a reaction partner. 

PMID- 24437520
TI  - Hygroscopic properties of internally mixed particles composed of NaCl and water
      soluble organic acids.
AB  - Atmospheric aging of naturally emitted marine aerosol often leads to formation of
      internally mixed particles composed of sea salts and water-soluble organic
      compounds of anthropogenic origin. Mixing of sea salt and organic components has
      profound effects on the evolving chemical composition and hygroscopic properties
      of the resulted particles, which are poorly understood. Here, we have studied
      chemical composition and hygroscopic properties of laboratory generated NaCl
      particles mixed with malonic acid (MA) and glutaric acid (GA) at different molar
      ratios using micro-FTIR spectroscopy, atomic force microscopy, and X-ray
      elemental microanalysis. Hygroscopic properties of internally mixed NaCl and
      organic acid particles were distinctly different from pure components and varied
      significantly with the type and amount of organic compound present. Experimental
      results were in a good agreement with the AIM modeling calculations of
      gas/liquid/solid partitioning in studied systems. X-ray elemental microanalysis
      of particles showed that Cl/Na ratio decreased with increasing organic acid
      component in the particles with MA yielding lower ratios relative to GA. We
      attribute the depletion of chloride to the formation of sodium malonate and
      sodium glutarate salts resulted by HCl evaporation from dehydrating particles. 

PMID- 24437521
TI  - Molecular interactions between mecamylamine enantiomers and the transmembrane
      domain of the human alpha4beta2 nicotinic receptor.
AB  - To characterize the binding sites of mecamylamine enantiomers on the
      transmembrane domain (TMD) of human (h) (alpha4)3(beta2)2 and (alpha4)2(beta2)3
      nicotinic acetylcholine receptors (AChRs), we used nuclear magnetic resonance
      (NMR), molecular docking, and radioligand binding approaches. The interactions of
      (S)-(+)- and (R)-(-)-mecamylamine with several residues, determined by high
      resolution NMR, within the halpha4beta2-TMD indicate different modes of binding
      at several luminal (L) and nonluminal (NL) sites. In general, the residues
      sensitive to each mecamylamine enantiomer are similar at both receptor
      stoichiometries. However, some differences were observed. The molecular docking
      experiments were crucial for delineating the location and orientation of each
      enantiomer in its binding site. In the (alpha4)2(beta2)3-TMD, (S)-(+)
      mecamylamine interacts with the L1 (i.e., between positions -3' and -5') and L2
      (i.e., between positions 16' and 20') sites, whereas the beta2-intersubunit
      (i.e., cytoplasmic end of two beta2-TMDs) and alpha4/beta2-intersubunit (i.e.,
      cytoplasmic end of alpha4-TM1 and beta2-TM3) sites are shared by both
      enantiomers. In the (alpha4)3(beta2)2-TMD, both enantiomers bind with different
      orientations to the L1' (closer to ring 2') and alpha4-intrasubunit (i.e., at the
      cytoplasmic ends of alpha4-TM1 and alpha4-TM2) sites, but only (R)-(-)
      mecamylamine interacts with the L2' (i.e., closer to ring 20') and alpha4-TM3
      intrasubunit sites. Our findings are important because they provide, for the
      first time, a structural understanding of the allosteric modulation elicited by
      mecamylamine enantiomers at each halpha4beta2 stoichiometry. This advancement
      could be beneficial for the development of novel therapies for the treatment of
      several neurological disorders. 

PMID- 24437522
TI  - Quality matters: extension of clusters of residues with good hydrophobic contacts
      stabilize (hyper)thermophilic proteins.
AB  - Identifying determinant(s) of protein thermostability is key for rational and
      data-driven protein engineering. By analyzing more than 130 pairs of
      mesophilic/(hyper)thermophilic proteins, we identified the quality (residue-wise
      energy) of hydrophobic interactions as a key factor for protein thermostability.
      This distinguishes our study from previous ones that investigated predominantly
      structural determinants. Considering this key factor, we successfully
      discriminated between pairs of mesophilic/(hyper)thermophilic proteins
      (discrimination accuracy: ~80%) and searched for structural weak spots in E. coli
      dihydrofolate reductase (classification accuracy: 70%). 

PMID- 24437526
TI  - Monodisperse and fast-responsive poly(N-isopropylacrylamide) microgels with open
      celled porous structure.
AB  - A simple and efficient method is developed to fabricate monodisperse and fast
      responsive poly(N-isopropylacrylamide) (PNIPAM) microgels with open-celled porous
      structure. First, numerous fine oil droplets are fabricated by homogeneous
      emulsification method and are then evenly dispersed inside monodisperse PNIPAM
      microgels as porogens via the combination of microfluidic emulsification and UV
      initiated polymerization methods. Subsequently, the embedded fine oil droplets
      inside the PNIPAM microgels are squeezed out upon stimuli-induced rapid volume
      shrinkage of the microgels; as a result, a spongelike open-celled porous
      structure is formed inside the PNIPAM microgels. The open-celled porous structure
      provides numerous interconnected free channels for the water transferring
      convectively inward or outward during the volume phase transition process of
      PNIPAM microgels; therefore, the response rates of the PNIPAM microgels with open
      celled porous structure are much faster than that of the normal ones in both
      thermo-responsive shrinking and swelling processes. Because of the fast
      responsive characteristics, the microgels with open-celled porous structure will
      provide ever better performances in their myriad applications, such as
      microsensors, microactuators, microvalves, and so on. 

PMID- 24437525
TI  - Observation of complete pressure-jump protein refolding in molecular dynamics
      simulation and experiment.
AB  - Density is an easily adjusted variable in molecular dynamics (MD) simulations.
      Thus, pressure-jump (P-jump)-induced protein refolding, if it could be made fast
      enough, would be ideally suited for comparison with MD. Although pressure
      denaturation perturbs secondary structure less than temperature denaturation,
      protein refolding after a fast P-jump is not necessarily faster than that after a
      temperature jump. Recent P-jump refolding experiments on the helix bundle lambda
      repressor have shown evidence of a <3 MUs burst phase, but also of a ~1.5 ms
      "slow" phase of refolding, attributed to non-native helical structure frustrating
      microsecond refolding. Here we show that a lambda-repressor mutant is nonetheless
      capable of refolding in a single explicit solvent MD trajectory in about 19 MUs,
      indicating that the burst phase observed in experiments on the same mutant could
      produce native protein. The simulation reveals that after about 18.5 MUs of
      conformational sampling, the productive structural rearrangement to the native
      state does not occur in a single swift step but is spread out over a brief series
      of helix and loop rearrangements that take about 0.9 MUs. Our results support the
      molecular time scale inferred for lambda-repressor from near-downhill folding
      experiments, where transition-state population can be seen experimentally, and
      also agrees with the transition-state transit time observed in slower folding
      proteins by single-molecule spectroscopy.

PMID- 24437527
TI  - Concise syntheses of meridianins and meriolins using a catalytic domino amino
      palladation reaction.
AB  - A synthesis of natural and synthetic members of the meridianin family of kinase
      inhibitory natural products has been developed. The sequence utilizes a variation
      of the Cacchi palladium-catalyzed domino reaction to efficiently construct the
      heterocyclic framework of the meridianins and meriolins from monocyclic
      precursors. 

PMID- 24437528
TI  - Large-area, conductive and flexible reduced graphene oxide (RGO) membrane
      fabricated by electrophoretic deposition (EPD).
AB  - A large-area, conductive, and flexible membrane made from the stabilized aqueous
      solution of reduced graphene oxide (RGO) is successfully fabricated using an
      electrophoretic deposition (EPD) method. A low-voltage operation of EPD (~3
      volts) allows a robust consolidation of RGO layers desirably aligned in the in
      plane direction through the cohesive electrophoretic squeezing force near the
      current collector. Transferring the deposited RGO layers to arbitrary substrates
      or achieving as a free-standing form, two methods of "chemical etching" and
      "electrochemical etching" are developed to detach the RGO layers from the EPD
      current collector without damaging the deposited RGO. Further reducing the free
      standing RGO membrane by thermal annealing up to 1000  degrees C, a graphite-like
      architecture is restored (d-spacing at 3.42 A with C/O ratio at 16.66) and the
      electrical conductivity increases as high as 5.51 * 10(5) S/m. The tightly
      consolidated and securely-detached RGO membrane allows the free-standing and
      flexible features and highly conductive characteristics, which are further
      developed during thermal treatment. Because of the facile scale-up nature of the
      EPD process and RGO solution, the developed methodology has a considerable
      potential to be applied to various energy storage devices, flexible conductive
      coatings, and other electrochemical systems. 

PMID- 24437529
TI  - Perspective on the use of perampanel and intravenous carbamazepine for
      generalized seizures.
AB  - INTRODUCTION: Several antiepileptic drugs are available for the treatment of
      epileptic patients. However, the treatment of some seizure types and novel drug
      formulations deserve further advances in epilepsy research. AREAS COVERED: The
      authors analyze the published evidence on the efficacy of perampanel against
      secondarily generalized seizures (SGS) and report the currently available
      development of intravenous (IV) formulations of carbamazepine (CBZ), commenting
      on their potential in the clinical setting. EXPERT OPINION: Perampanel is the
      first noncompetitive AMPA receptor antagonist to be approved as adjunctive
      treatment in patients with partial-onset (focal) seizures (POS) with or without
      secondary generalization. Apart from its efficacy and safety on POS, a consistent
      body of evidence supports its efficacy in SGS at a minimum dose of 8 mg/day;
      however, such dose appears close to the best-tolerated dose. CBZ is a poorly
      water-soluble compound; many efforts to develop a parenteral formulation have not
      been successful so far. Novel IV CBZ formulations seem to exhibit favorable
      pharmacokinetics along with good tolerability in animal models and in patients
      taking oral CBZ. Further studies are needed to assess whether larger doses will
      be as well tolerated, allowing IV CBZ to be used as bridge therapy when the oral
      route is not feasible or in patients naive to CBZ.

PMID- 24437530
TI  - Opioids in the treatment of postoperative pain: old drugs with new options?
AB  - New approved options with opioids in the postoperative setting may include new
      ways of administration, new combinations with other drugs and new opioid drugs.
      Newly approved devices for administration include sublingual sufentanil dispenser
      and transdermal iontophoretic fentanyl, with the purpose of almost mimicking the
      rapid and reliable onset of intravenous (IV) administration, without the problems
      of an ongoing IV cannula and cumbersome equipment. Still, potential problems of
      overdosing and misuse must be in focus when these devices come into use.
      Tapentadol is a new partial u-receptor opioid agonist with a combined action on
      norepinephrine-induced analgesia, representing a promising drug in terms of less
      side effects at equianalgesic doses compared with pure agonists. The mixture of
      different opioids given together, such as oxycodone and morphine, for oral use
      may also have some analgesic synergy with an improved side-effect profile,
      although more studies are needed. Oral oxycodone is a reliable oral opioid
      option, but when combined with paracetamol in the same tablet or mixture, care
      should also be taken to avoid serious side effects from inadvertent paracetamol
      overdose. 

PMID- 24437531
TI  - New pharmacological treatments for methicillin-resistant Staphylococcus aureus
      infections.
AB  - INTRODUCTION: Despite available treatment options for methicillin-resistant
      Staphylococcus aureus (MRSA), the morbidity and mortality attributed to the
      diverse infection manifestations of this pathogen remain high. More anti-MRSA
      agents are needed as options for treatment of these infections. Ideally, these
      new agents would be rapidly bactericidal for bloodstream clearance in septic
      patients, have few toxicities, be active against MRSA in biofilms, be easy to
      administer, and have oral bioavailability. AREAS COVERED: This review focuses on
      MRSA agents in Phase III trials or antibiotics currently in the market, which are
      being studied for new indications. For each agent, the antimicrobial potency
      against MRSA, pharmacokinetic and pharmacodynamic considerations and approved and
      potential new indications are presented. The role of novel combination therapies
      is also introduced. EXPERT OPINION: The new lipoglycopeptides oritavancin,
      telavancin and dalbavancin have the potential to make a large impact on the
      treatment of MRSA due to unique pharmacokinetic/pharmacodynamic properties and
      proposed dosing regimens. Other new agents (omadacycline and tedizolid) as well
      as revisited older agents (fosfomycin and fusidic acid) appear promising but
      require further study for their potential role. Combination therapy may improve
      outcomes in patients with high MRSA infection burden or when patient or pathogen
      factors predict a worse outcome with monotherapy.

PMID- 24437536
TI  - Identification of genes essential for the biogenesis of quinohemoprotein amine
      dehydrogenase.
AB  - The structural genes encoding quinohemoprotein amine dehydrogenase (QHNDH) in
      Gram-negative bacteria constitute a polycistronic operon together with several
      nearby genes, which are collectively termed "qhp". We previously showed that the
      qhpD gene, which lies between qhpA and qhpC (encoding the alpha and gamma
      subunits of QHNDH, respectively), and the qhpE gene, which follows qhpB (encoding
      the beta subunit), both encode enzymes specifically involved in the
      posttranslational modification of the gamma subunit and are hence essential for
      QHNDH biogenesis in Paracoccus denitrificans [Ono, K., et al. (2006) J. Biol.
      Chem. 281, 13672-13684; Nakai, T., et al. (2012) J. Biol. Chem. 287, 6530-6538].
      Here we further demonstrate that the qhpF gene, which follows qhpE, and the qhpG
      and qhpR genes, peripherally located in the complementary strand, are also
      indispensable for QHNDH biogenesis. The qhpF gene encodes an efflux ABC
      transporter, which probably translocates the gamma subunit into the periplasm in
      a process coupled with hydrolysis of ATP. The qhpG gene encodes a putative FAD
      dependent monooxygenase, which is required for the generation of the quinone
      cofactor in the gamma subunit. Finally, the qhpR gene encodes an AraC family
      transcriptional regulator, which activates expression of the qhp operon in
      response to the addition of n-butylamine to the culture medium. Database analysis
      of the qhp genes reveals that they are very widely distributed, not only in many
      Gram-negative species but also in a few Gram-positive bacteria. 

PMID- 24437539
TI  - Daily ambient NO2 concentration predictions using satellite ozone monitoring
      instrument NO2 data and land use regression.
AB  - Although ground measurements have contributed to revealing the association
      between ambient air pollution and health effects in epidemiological studies,
      exposure measurement errors are likely to be caused because of the sparse spatial
      distribution of ground monitors. In this study, we estimate daily ground NO2
      concentrations in the New England region, U.S., for the period 2005-2010 using
      satellite remote sensing data in combination with land use regression. To
      estimate ground-level NO2 concentrations, we constructed a mixed effects model by
      taking advantage of spatial and temporal variability in satellite Ozone
      Monitoring Instrument (OMI) tropospheric column NO2 densities. Using fine-scale
      land use parameters, we derived NO2 concentrations at point locations, which can
      be further used for subject-specific exposure estimates in epidemiological
      studies. A mixed effects model showed a reasonably high predictive power for
      daily NO2 concentrations (cross-validation R(2) = 0.79). We observed that the
      model performed similarly in each season, year, and state. The spatial patterns
      of model estimates reflected emission source areas (such as high
      populated/traffic areas) in the study region and revealed the seasonal
      characteristics of NO2. This study suggests that a combination of satellite
      remote sensing and land use regression can be useful for both spatially and
      temporally resolved exposure assessments of NO2. 

PMID- 24437541
TI  - Variation and transmission of Sonoran wild food knowledge in southern Arizona.
AB  - Since knowledge about wild foods is thought to be declining in younger
      generations worldwide, this study's objective was to describe variation in
      Sonoran wild food knowledge in southern Arizona between adults (n = 19) and
      students (n = 110) using free lists, an identification exercise, and structured
      interviews. There are fundamental differences in the quantity and quality of
      knowledge that adults and students have about wild desert foods. Adults know more
      native species, specific names, and correctly identify Sonoran wild foods twice
      as often as students. Fewer direct nature experiences in the younger generation
      may account for the observed variation in wild food knowledge.

PMID- 24437542
TI  - Mutandabota, a food product from Zimbabwe: processing, composition, and
      socioeconomic aspects.
AB  - We evaluated processing technology, composition, and socioeconomic significance
      of mutandabota, a food product made by mixing cow's or goat's milk with dry
      baobab fruit pulp. Mutandabota production is a gendered activity dominated by
      women. Nutrient content was (g 100 g(-1) w.b) protein 4.8 +/- 1, fat 2.8 +/- 0.9,
      fiber 1.1 +/- 0.4, ash 0.9 +/- 0.2, carbohydrates 20 +/- 1.7, moisture 70.4 +/-
      3.7, and vitamin C 80 +/- 25 mg/100g. Microbiological load (log cfu ml(-1)) was
      high, 4.7 +/- 1.2 mesophilic bacteria, 5.3 +/- 2.1 lactic acid bacteria, and 5.0
      +/- 1.3 yeasts and molds. The pH of milk was 6.7 and the final pH of mutandabota
      was 3.5 +/- 0.1. Mutandabota is a major source of proteins and vitamin C. Its
      microbiological quality needs evaluation. 

PMID- 24437543
TI  - Comparison of two indices of diet quality with acculturation factors and
      demographics in Haitian Americans.
AB  - This study examined associations of language preference and length of stay in the
      United States and diet among 132 Haitian Americans aged >=35, born in Haiti. Two
      dietary indices, Healthy Eating Index (HEI) and Alternative Healthy Eating Index
      (AHEI), were used to assess dietary quality. Years in the United States (>15
      years; B = 0.063, p = .012) and female gender (B = 5.63, p = .028) were
      positively associated with AHEI. Lower HEI scores were associated with speaking
      no English (B = -6.11, p = .026). Participants reporting an income under
      20,000/yr had lower AHEI scores (B = -7.63, p = .014). Concurrent use of these
      indices would provide a screening tool for nutrition intervention. Public health
      programs targeting low-cost resources, such as community gardening, are
      recommended to reduce health disparities among this population.

PMID- 24437544
TI  - Country-of-origin labeling prior to and at the point of purchase: an exploration
      of the information environment in Baltimore City grocery stores.
AB  - The country-of-origin labeling (COOL) law requires United States grocers to
      indicate the origin and procurement method (farm-raised or wild-caught) for
      seafood. This study explored the presentation of COOL on fresh, frozen, packaged,
      and unpackaged seafood in Baltimore City grocery stores. Eight stores were
      visited bi-monthly to photograph seafood labels, and circulars were collected
      weekly from fourteen stores over three months. Ninety-six percent of products
      were labeled correctly. Forty-eight percent of advertisements included COOL.
      While in-store labels did not highlight COOL, advertising featured references to
      domestic and wild-caught seafood, signaling to customers that these are high
      value product qualities. 

PMID- 24437545
TI  - Dietary quality of elders and children is interdependent in Taiwanese
      communities: a NAHSIT mapping study.
AB  - Dietary quality may exhibit intergenerational associations in Taiwanese
      communities. Nutrition and Health Surveys in Taiwan (NAHSIT) for children and
      elders (1999-2002) were mapped for coincident locality and ethnicity with Geo
      Gadget. Communities were characterized ecologically. Dietary quality was assessed
      by the Youth Healthy Eating Index-Taiwan (YHEI-TW) for children and Overall
      Dietary Index-Revised (ODI-R) for elders. Hierarchical regression analysis was
      used. Elderly ODI-R was linked with the overall child YHEI-TW (p < .001). When
      ODI-R increased 1 unit, the child YHEI-TW improved 0.232 and 0.134 YHEI-TW units
      with men and women, respectively. Dietary quality of community elders is related
      to that of children. 

PMID- 24437546
TI  - Bush tucker, shop tucker: production, consumption, and diet at an Aboriginal
      outstation.
AB  - Foraging models have rarely been used to address how behavior is altered by the
      presence of non-foraged foods. Here, choices of store-bought and hunted foods in
      one Aboriginal community are analyzed. Hunting occurs frequently, but community
      residents also purchase food from the shop. Increases in the frequency of hunting
      certain large and small prey are associated with reduced access to food in the
      shop. Higher-variance hunt types are not associated with shop purchases, but
      continue to be acquired due to their cultural significance. The variation in
      these results highlights the complexity of dietary behavior in a mixed economy. 

PMID- 24437547
TI  - A formal, one-pot beta-chlorination of primary alcohols and its utilization in
      the transformation of terpene feedstock and the synthesis of a C2-symmetrical
      terminal bis-epoxide.
AB  - A one-pot transformation of alkan-1-ols into 2-chloroalkan-1-ols is described. As
      a practical application, terpene-derived primary alcohols were converted into
      semiochemicals such as olfactory lactones (aerangis lactone, whisky lactone, and
      cognac lactone) and pheromones (cruentol and ferrugineol). Using heptane-1,7-diol
      as a bifunctional substrate, the corresponding bis-epoxide was synthesized by
      bidirectional synthesis in good yield and high enantioselectivity. 

PMID- 24437550
TI  - Enrichment analysis for discovering biological associations in phenotypic
      screens.
AB  - A phenotypic screen (PS) is used to identify compounds causing a desired
      phenotype in a complex biological system where mechanisms and targets are largely
      unknown. Deconvoluting the mechanism of action of actives and identification of
      relevant targets and pathways remains a formidable challenge. Current methods
      fail to use the rich information available regarding compounds and their targets
      in a systematic way for this deconvolution. We have developed an enrichment
      analysis algorithm to identify targets associated with the desired phenotype in a
      rigorous data-driven manner using actives and hundreds of thousands of inactives
      in a PS, as well as results of thousands of available legacy target-based screens
      in an institution. Our method quantifies association between the PS and targets
      while reducing sampling bias, which leads to identification of novel targets,
      additional chemical matter, and appropriate assays. Its use is illustrated using
      two examples from our laboratories: TRAIL and DNA fragmentation. Enrichment
      analysis of these PSs is discussed using both biological pathway analysis and
      known cell biology to demonstrate the value of our method. We believe this
      enrichment analysis method is an indispensable tool for the analysis of PSs. 

PMID- 24437551
TI  - Targeted theranostic platinum(IV) prodrug with a built-in aggregation-induced
      emission light-up apoptosis sensor for noninvasive early evaluation of its
      therapeutic responses in situ.
AB  - Targeted drug delivery to tumor cells with minimized side effects and real-time
      in situ monitoring of drug efficacy is highly desirable for personalized
      medicine. In this work, we report the synthesis and biological evaluation of a
      chemotherapeutic Pt(IV) prodrug whose two axial positions are functionalized with
      a cyclic arginine-glycine-aspartic acid (cRGD) tripeptide for targeting integrin
      alphavbeta3 overexpressed cancer cells and an apoptosis sensor which is composed
      of tetraphenylsilole (TPS) fluorophore with aggregation-induced emission (AIE)
      characteristics and a caspase-3 enzyme specific Asp-Glu-Val-Asp (DEVD) peptide.
      The targeted Pt(IV) prodrug can selectively bind to alphavbeta3 integrin
      overexpressed cancer cells to facilitate cellular uptake. In addition, the Pt(IV)
      prodrug can be reduced to active Pt(II) drug in cells and release the apoptosis
      sensor TPS-DEVD simultaneously. The reduced Pt(II) drug can induce the cell
      apoptosis and activate caspase-3 enzyme to cleave the DEVD peptide sequence. Due
      to free rotation of the phenylene rings, TPS-DEVD is nonemissive in aqueous
      media. The specific cleavage of DEVD by caspase-3 generates the hydrophobic TPS
      residue, which tends to aggregate, resulting in restriction of intramolecular
      rotations of the phenyl rings and ultimately leading to fluorescence enhancement.
      Such noninvasive and real-time imaging of drug-induced apoptosis in situ can be
      used as an indicator for early evaluation of the therapeutic responses of a
      specific anticancer drug. 

PMID- 24437552
TI  - Acrylated poly(3,4-propylenedioxythiophene) for enhancement of lifetime and
      optical properties for single-layer electrochromic devices.
AB  - We utilized our in situ method for the one-step assembly of single-layer
      electrochromic devices (ECDs) with a 3,4-propylenedioxythiophene (ProDOT)
      acrylate derivative, and long-term stability was achieved. By coupling the
      electroactive monomer to the cross-linkable polymer matrix, preparation of the
      electrochromic ProDOT polymer can occur followed by UV cross-linking. Thus, we
      achieve immobilization of the unreacted monomer, which prevents any degradative
      processes from occurring at the counter electrode. This approach eliminated spot
      formation in the device and increased stability to over 10 000 cycles when
      compared to 500 cycles with conventional ProDOT devices wherein the monomer is
      not immobilized. The acrylated electrochromic polymer exhibits similar
      electrochromic properties as conventional ProDOT devices, such as photopic
      contrast (48% compared to 46%) and switch speed (both 2 s). This method can be
      applied to any one-layer electrochromic system where improved stability is
      desired. 

PMID- 24437553
TI  - Electrophoretic deposition and characterization of transparent nanocomposite
      films of YVO4:Bi3+,Eu3+ nanophosphor and silicone-modified acrylic resin.
AB  - We fabricated nanocomposite films from an aqueous suspension of red-emitting
      YVO4:Bi(3+),Eu(3+) nanoparticles (hydrodynamic size: 22 +/- 6 nm) and silicone
      modified acrylic resin nanoparticles of (60 +/- 15 nm) by electrophoretic
      deposition under application of a constant voltage. The nanocomposite films were
      formed from these negatively charged nanoparticles on ITO-coated glass substrates
      on the anodic side at the volume ratio of nanophosphor:resin ~ 40:60. According
      to transmission electron microscopy observations, the YVO4:Bi(3+),Eu(3+)
      nanoparticles are well-dispersed around the resin nanoparticles. The fabricated
      films are transparent to the naked eye under white light because both
      nanoparticles show no absorption and low light scattering in the visible region.
      A silicone-modified acrylic resin film without the nanophosphor exhibits no
      absorption in the UV region (>300.0 nm). However, the fabricated nanocomposite
      films show near-UV absorption owing to the interband transition between the
      valence band and the conduction band of the YVO4:Bi(3+),Eu(3+) nanoparticles. A
      sharp emission peak corresponding to the (5)D0 -> (7)F2 transition of Eu(3+) is
      observed at 619.5 nm, under 365.0 nm excitation, for each nanocomposite film. The
      photoluminescence intensity at 619.5 nm under 365.0 nm excitation is proportional
      to 1-10(-OD) (OD: optical density at 365.0 nm) for film thicknesses <=6 MUm. This
      is attributed to the low light scattering from both nanoparticles in the
      nanocomposite film. Conversely, the observed photoluminescence intensity for film
      thicknesses >6 MUm is higher than the value expected from the proportional
      relationship. This suggests that the excitation of the nanophosphors efficiently
      occurs due to multiple scattering of excitation light. 

PMID- 24437554
TI  - A new strategy to construct acyclic nucleosides via Ag(I)-catalyzed addition of
      pronucleophiles to 9-allenyl-9H-purines.
AB  - A new strategy to construct acyclic nucleosides with diverse side chains was
      developed. With Ag(I) salts as catalysts, the hydrocarboxylation, hydroamination,
      and hydrocarbonation reactions proceeded well, affording acyclic nucleosides in
      good yields (41 examples, 60-98% yields). Meanwhile, these reactions exhibited
      high chemoselectivities and E-selectivities. 

PMID- 24437562
TI  - Presurgical Unilateral Cleft Lip Anthropometrics and the Presence of Dental
      Anomalies.
AB  - OBJECTIVE: To investigate associations between cleft lip anthropometrics and
      dental anomalies in the permanent dentition in unilateral cleft lip patients.
      DESIGN: Retrospective cross-sectional study. PATIENTS: Children with unilateral
      clefts of the lip, with or without cleft palate. METHODS: Anthropometric lip
      measurements, made immediately prior to lip repair, were available for each
      patient. The presence of dental anomalies in the permanent dentition was assessed
      radiographically. The presence of associations between anthropometric lip
      measurements and prevalence rates of different dental anomalies were determined
      using logistic regression analyses. RESULTS: In the 122 included patients, the
      cleft lateral lip element was deficient in height in 80% and in transverse length
      in 84% of patients. Patients with more deficient cleft side lateral lip height
      and less deficient cleft side lateral lip transverse length were more likely to
      present with cleft side maxillary lateral incisor agenesis. On the other hand,
      patients with a less deficient cleft side lateral lip height and more deficient
      cleft side lateral lip transverse length were more likely to present with a cleft
      side supernumerary maxillary lateral incisor. When looking only at incomplete
      clefts, the cleft side lateral lip transverse length deficiency was more
      predictive of the presence of supernumerary maxillary lateral incisors (P =
      .030), while for complete clefts, the cleft side lateral lip height deficiency
      was more predictive of the presence of maxillary lateral incisor agenesis (P =
      .035). CONCLUSIONS: In patients with unilateral clefts, cleft lip anthropometrics
      have a predictive role in determining the occurrence of dental anomalies.

PMID- 24437563
TI  - The need for orthognathic surgery in nonsyndromic patients with repaired isolated
      cleft palate.
AB  - OBJECTIVE: To determine the frequency of need for orthognathic surgery among
      nonsyndromic patients with isolated cleft palate repaired during infancy at The
      Hospital for Sick Children in Toronto, Canada. DESIGN: Retrospective cohort
      study. PATIENTS: PATIENTS with nonsyndromic isolated cleft palate born between
      1970 and 1997 with available records including a lateral cephalometric radiograph
      taken at >=15 years of age. METHODS: PATIENTS who had undergone or were being
      prepared for orthognathic surgery were automatically counted as requiring
      surgery. For the remaining patients, lateral cephalometric radiographs were
      traced and analyzed. Arbitrarily set cephalometric criteria were used to identify
      the "objective" need for orthognathic surgery. RESULTS: Of the 189 patients
      identified with nonsyndromic isolated cleft palate and for whom records were
      available, 25 (13.2%) were deemed to require orthognathic surgery. Of the
      surgical cohort, 92% required surgical correction for a Class III malocclusion.
      Similar percentages of males and females required orthognathic surgery. An
      apparently greater proportion of patients of Asian background (18.5%) than of
      white background (10.6%) required surgery, but this difference was not
      significant (P = .205). CONCLUSIONS: The current results suggest that
      approximately one in eight patients at our institution with nonsyndromic isolated
      cleft palate requires orthognathic surgery. There is a tendency for this to be
      higher in patients of Asian descent and lower in patients of white descent.
      Variability in extent, severity, and phenotype of the cleft, which may be
      attributed largely to genetics, may play an important role in dictating the need
      for orthognathic surgery.

PMID- 24437566
TI  - Dicobalt-MU-oxo polyoxometalate compound, [(alpha(2)-P2W17O61Co)2O](14-): a
      potent species for water oxidation, C-H bond activation, and oxygen transfer.
AB  - High-valent oxo compounds of transition metals are often implicated as active
      species in oxygenation of hydrocarbons through carbon-hydrogen bond activation or
      oxygen transfer and also in water oxidation. Recently, several examples of cobalt
      catalyzed water oxidation have been reported, and cobalt(IV) species have been
      suggested as active intermediates. A reactive species, formally a dicobalt(IV)-MU
      oxo polyoxometalate compound [(alpha2-P2W17O61Co)2O](14-), [(POMCo)2O], has now
      been isolated and characterized by the oxidation of a monomeric [alpha2
      P2W17O61Co(II)(H2O)](8-), [POMCo(II)H2O], with ozone in water. The crystal
      structure shows a nearly linear Co-O-Co moiety with a Co-O bond length of ~1.77
      A. In aqueous solution [(POMCo)2O] was identified by (31)P NMR, Raman, and UV-vis
      spectroscopy. Reactivity studies showed that [(POMCo)2O]2O] is an active compound
      for the oxidation of H2O to O2, direct oxygen transfer to water-soluble
      sulfoxides and phosphines, indirect epoxidation of alkenes via a Mn porphyrin,
      and the selective oxidation of alcohols by carbon-hydrogen bond activation. The
      latter appears to occur via a hydrogen atom transfer mechanism. Density
      functional and CASSCF calculations strongly indicate that the electronic
      structure of [(POMCo)2O]2O] is best defined as a compound having two cobalt(III)
      atoms with two oxidized oxygen atoms. 

PMID- 24437567
TI  - Synthesis of (+)-luzofuran and (-)-ancistrofuran.
AB  - The first synthesis of the furan-containing snyderane, (+)-luzofuran, is
      reported. The key step in this approach was an electrophilic brominative
      cyclization, which was accomplished using a nucleophilic N-heterocycle-flanked
      phosphoramidite catalyst in combination with the common laboratory reagent N
      bromosuccinimide. 

PMID- 24437570
TI  - Polarizable six-point water models from computational and empirical optimization.
AB  - Troster et al. (J. Phys. Chem B 2013, 117, 9486-9500) recently suggested a mixed
      computational and empirical approach to the optimization of polarizable molecular
      mechanics (PMM) water models. In the empirical part the parameters of Buckingham
      potentials are optimized by PMM molecular dynamics (MD) simulations. The
      computational part applies hybrid calculations, which combine the quantum
      mechanical description of a H2O molecule by density functional theory (DFT) with
      a PMM model of its liquid phase environment generated by MD. While the static
      dipole moments and polarizabilities of the PMM water models are fixed at the
      experimental gas phase values, the DFT/PMM calculations are employed to optimize
      the remaining electrostatic properties. These properties cover the width of a
      Gaussian inducible dipole positioned at the oxygen and the locations of massless
      negative charge points within the molecule (the positive charges are attached to
      the hydrogens). The authors considered the cases of one and two negative charges
      rendering the PMM four- and five-point models TL4P and TL5P. Here we extend their
      approach to three negative charges, thus suggesting the PMM six-point model TL6P.
      As compared to the predecessors and to other PMM models, which also exhibit
      partial charges at fixed positions, TL6P turned out to predict all studied
      properties of liquid water at p0 = 1 bar and T0 = 300 K with a remarkable
      accuracy. These properties cover, for instance, the diffusion constant,
      viscosity, isobaric heat capacity, isothermal compressibility, dielectric
      constant, density, and the isobaric thermal expansion coefficient. This success
      concurrently provides a microscopic physical explanation of corresponding
      shortcomings of previous models. It uniquely assigns the failures of previous
      models to substantial inaccuracies in the description of the higher electrostatic
      multipole moments of liquid phase water molecules. Resulting favorable properties
      concerning the transferability to other temperatures and conditions like the
      melting of ice are also discussed.

PMID- 24437571
TI  - Seawater intrusion into groundwater aquifer through a coastal lake - complex
      interaction characterised by water isotopes (2)H and (18)O.
AB  - The present study investigates the complex interactions among surface waters,
      groundwaters and a coastal lake in northeastern Greece, using their stable
      isotopic composition (delta(18)O, delta(2)H) in combination with hydrogeological
      and hydrochemical data. Seasonal and spatial trends of water isotopes were
      studied and revealed that all water bodies in the study area interact. It was
      also shown that the aquifer's increased salinity is not due to fossil water from
      past geological periods, but is attributed to brackish lake water intrusion into
      the aquifer induced by the extensive groundwater pumping for irrigation purposes.
      Quantification of the contribution of the lake to the aquifer was achieved using
      the simple dilution formula. The isotopic signatures of the seawater and the
      groundwaters are considerably different, so there is a very little possibility of
      direct seawater intrusion into the aquifer. 

PMID- 24437572
TI  - Therapeutic targets for rheumatoid arthritis: Progress and promises.
AB  - Recent therapeutic advancements in understanding of molecular and cellular
      mechanisms of rheumatoid arthritis (RA) have highlighted the strategies that aim
      to inhibit the harmful effects of up-regulated cytokines or other inflammatory
      mediators and to inhibit their associated signaling events. The utility of
      cytokine as therapeutic targets in RA has been unequivocally demonstrated by the
      success of tumor necrosis factor (TNF)-alpha blockade in clinical practice.
      Partial and non-responses to TNF-alpha blocking agents, however, together with
      the increasing clinical drive to remission induction, requires that further
      therapeutic targets be identified. Numerous proinflammatory mediators with their
      associated cell signaling events have now been demonstrated in RA, including
      interleukin (IL)-1 and IL-12 superfamilies. Continued efforts are ongoing to
      target IL-6, IL-15 and IL-17 in clinical trials with promising data emerging. In
      the present review, we focus on IL-7, IL-18, IL-32 and IL-10 family of cytokines
      (IL-19, IL-20 and IL-22) as they are implicated in contributing to the
      pathogenesis of RA, which could be targeted and offer new therapeutic options for
      RA therapy. Recent evidences also suggest that multiligand receptor for advanced
      glycation end products (RAGE), several adipokines and various components of
      immune system play a critical role in the pathophysiology of RA; therefore we
      have also highlighted them as therapeutic targets for RA therapy. Components of
      subcellular pathways, involve in nuclear transcription factor (NF)-kappaB,
      mitogen-activated protein kinases (MAPKs) and the Janus kinase-signal transducer
      and activator of transcription (JAK-STAT) pathway have also been discussed and
      offer several novel potential therapeutic opportunities for RA.

PMID- 24437577
TI  - Composition and topology of activity cliff clusters formed by bioactive
      compounds.
AB  - The assessment of activity cliffs has thus far mostly focused on compound pairs,
      although the majority of activity cliffs are not formed in isolation but in a
      coordinated manner involving multiple active compounds and cliffs. However, the
      composition of coordinated activity cliff configurations and their topologies are
      unknown. Therefore, we have identified all activity cliff configurations formed
      by currently available bioactive compounds and analyzed them in network
      representations where activity cliff configurations occur as clusters. The
      composition, topology, frequency of occurrence, and target distribution of
      activity cliff clusters have been determined. A limited number of large cliff
      clusters with unique topologies were identified that were centers of activity
      cliff formation. These clusters originated from a small number of target sets.
      However, most clusters were of small to moderate size. Three basic topologies
      were sufficient to describe recurrent activity cliff cluster motifs/topologies.
      For example, frequently occurring clusters with star topology determined the
      scale-free character of the global activity cliff network and represented a
      characteristic activity cliff configuration. Large clusters with complex topology
      were often found to contain different combinations of basic topologies. Our study
      provides a first view of activity cliff configurations formed by currently
      available bioactive compounds and of the recurrent topologies of activity cliff
      clusters. Activity cliff clusters of defined topology can be selected, and from
      compounds forming the clusters, SAR information can be obtained. The SAR
      information of activity cliff clusters sharing a/one specific activity and
      topology can be compared. 

PMID- 24437575
TI  - Crystal structures of type I dehydroquinate dehydratase in complex with quinate
      and shikimate suggest a novel mechanism of Schiff base formation.
AB  - A component of the shikimate biosynthetic pathway, dehydroquinate dehydratase
      (DHQD) catalyzes the dehydration of 3-dehydroquniate (DHQ) to 3-dehydroshikimate.
      In the type I DHQD reaction mechanism a lysine forms a Schiff base intermediate
      with DHQ. The Schiff base acts as an electron sink to facilitate the catalytic
      dehydration. To address the mechanism of Schiff base formation, we determined
      structures of the Salmonella enterica wild-type DHQD in complex with the
      substrate analogue quinate and the product analogue shikimate. In addition, we
      determined the structure of the K170M mutant (Lys170 being the Schiff base
      forming residue) in complex with quinate. Combined with nuclear magnetic
      resonance and isothermal titration calorimetry data that revealed altered binding
      of the analogue to the K170M mutant, these structures suggest a model of Schiff
      base formation characterized by the dynamic interplay of opposing forces acting
      on either side of the substrate. On the side distant from the substrate 3
      carbonyl group, closure of the enzyme's beta8-alpha8 loop is proposed to guide
      DHQ into the proximity of the Schiff base-forming Lys170. On the 3-carbonyl side
      of the substrate, Lys170 sterically alters the position of DHQ's reactive ketone,
      aligning it at an angle conducive for nucleophilic attack. This study of a type I
      DHQD reveals the interplay between the enzyme and substrate required for the
      correct orientation of a functional group constrained within a cyclic substrate. 

PMID- 24437578
TI  - Intramolecular dearomatizing [3 + 2] annulation of alpha-imino carbenoids with
      aryl rings furnishing 3,4-fused indole skeletons.
AB  - The rhodium-catalyzed dearomatizing [3 + 2] annulation reaction of 4-(3
      arylpropyl)-1,2,3-triazoles is described. It provides a straightforward synthetic
      pathway from simple 5-aryl-1-alkynes leading to tricyclic 3,4-fused
      dihydroindoles via the corresponding 1,2,3-triazoles. 

PMID- 24437579
TI  - Anionic branched surfactants as alternative denaturing agents for protein
      separations.
AB  - Denaturation of a group of model proteins of diverse size and composition with
      three branched alkyl surfactants-sodium 2-ethylhexyl sulfate (2-EHS), sodium 3,7
      dimethyloctyl sulfate (3,7-DMOS), and sodium 2-butyloctyl sulfate (2-BOS)-has
      been investigated using circular dichroism (CD), small-angle X-ray scattering,
      and polyacrylamide gel electrophoresis (PAGE). Circular dichroism reveals that 2
      BOS disrupts to a higher extent the secondary structure for most of the proteins.
      Also, it is found that upon adsorption the shape of the protein-surfactant
      complexes varies from "pearl necklace" to ellipsoidal depending on the surfactant
      that is used. Macroscopic separations also reveal that branching sodium alkyl
      sulfates with n-butyl (2-BOS) and n-methyl (3,7-DMOS) groups significantly
      affects their performance in PAGE. 3,7-DMOS and 2-BOS result in anomalous
      migrations that deviate from the expected electrophoretic mobility. A combined
      interpretation of spectroscopy, scattering, and polyacrylamide gel
      electrophoresis suggests that 2-BOS promotes stronger modification of proteins
      during denaturation. The findings in this work aim to improve protein
      electrophoretic separations and the design of novel surfactants. 

PMID- 24437582
TI  - Evidence for the cyclic CN2 carbene in solution.
AB  - Diazirinylidene (c-CN2) is formally the simplest of the N-heterocyclic carbenes.
      The intermediacy of this elusive species in the fragmentation of butyl 3
      bromodiazirine-3-carboxylate (1a) with pent-4-en-1-ols and their sodium alkoxides
      in DMF is supported by the formation of 2-oxabicyclo[4.1.0]heptanes and
      dipentenoxymethanes. These products result from an intramolecular [2 + 1]
      cycloaddition and O-H insertion, respectively, of pentenoxymethylenes suggested
      to originate from the reaction of the electrophilic c-CN2 with an alkoxide ion.
      The reaction of 1a with primary or secondary amines in methanol affords the
      corresponding 3-bromodiazirine-3-carboxamides. 

PMID- 24437583
TI  - Cleft Lip and/or Palate and Auricular Malformations.
AB  - OBJECTIVE: To study the relationship between cleft lip and/or palate and
      auricular malformations in Finnish patients with cleft. DESIGN: Retrospective
      analysis of patients with an external ear malformation and either a cleft lip
      with or without a cleft palate (CL+/-P) or an isolated cleft palate (CP).
      SETTING: Tertiary referral clinic. PATIENTS: Review of hospital records of 100
      patients from the register of 8200 patients with cleft in the Cleft and
      Craniofacial Centre at the Helsinki University Central Hospital. MAIN OUTCOME
      MEASURES: Proportions of variable auricular malformations among CL+/-P and CP
      patients. RESULTS: Microtia is the most common auricular malformation among
      patients with cleft and is almost equally prevalent with both CL+/-P and CP. The
      prevalence of microtia increases as the severity of CL+/-P increases. The
      combination of microtia and CL+/-P or CP is frequently found with both oculo
      auriculo-vertebral spectrum and Treacher Collins syndrome. CONCLUSIONS: Microtia
      seems to be the most common auricular malformation among patients with cleft. The
      prevalence of microtia seems to increase as the severity of CL+/-P increases,
      whereas in isolated CP microtia seems to occur independently.

PMID- 24437585
TI  - Effects of lip repair on maxillofacial morphology in patients with unilateral
      cleft lip with or without cleft palate.
AB  - Objective : To evaluate the effects of lip repair on maxillofacial development of
      patients with unilateral cleft lip with or without cleft palate. Design :
      Retrospective. Patients : A total of 75 patients were recruited, including 38
      surgical patients with complete unilateral cleft lip and alveolus and 37 patients
      with complete unilateral cleft lip and palate who had lip but not palate repair.
      As controls, 38 patients with no cleft were selected. All subjects were divided
      according to two growth stages: before the pubertal peak (GS1) and after the
      pubertal peak (GS2). Interventions : Lateral cephalograms of all subjects were
      obtained. Main Outcome Measures : Cephalograms were analyzed and compared in the
      study and control groups. Results : The patients with unilateral cleft lip and
      palate in both GS1 and GS2 demonstrated an almost normal maxillary and mandibular
      growth with retroclined maxillary incisors. The patients with unilateral cleft
      lip and palate showed a shorter length of maxilla, a more clockwise-rotated
      mandible, and retroclined maxillary incisors. Conclusions : There was an almost
      normal maxillary and mandibular growth but retroclined maxillary incisors in
      patients with cleft lip with or without cleft palate who had received lip repair
      only, indicating that lip repair may not have a negative impact on the
      maxillofacial development and influences only the inclination of the maxillary
      incisors. The shorter anterior-posterior maxillary length and larger gonial angle
      in patients with unilateral cleft lip and palate compared with those in patients
      with unilateral cleft lip and alveolus suggest that these variations in maxillary
      and mandibular growth may be a consequence of the cleft itself. 

PMID- 24437584
TI  - Association of WNT9B Gene Polymorphisms With Nonsyndromic Cleft Lip With or
      Without Cleft Palate in Brazilian Nuclear Families.
AB  - OBJECTIVE: Nonsyndromic cleft lip with or without cleft palate (NSCL+/-P) is a
      common craniofacial anomaly of complex etiology in people. WNT pathway genes have
      important roles during craniofacial development, and an association of WNT genes
      with NSCL+/-P has been demonstrated in different populations. The aim of this
      study was to evaluate the association between polymorphisms in WNT3 and WNT9B
      genes and CL/P in Brazilian families. PATIENTS: Seventy nuclear families composed
      of an affected child and the child's unaffected parents were examined clinically.
      Saliva samples were collected for molecular analyses. DESIGN: Three single
      nucleotide polymorphisms (SNPs) in the WNT3 gene and two in WNT9B were
      investigated in real-time polymerase chain reaction using TaqMan chemistry. The
      Family-Based Association Test and the transmission disequilibrium test were used
      to verify the association between each marker allele and NSCL+/-P. The level of
      significance was established at P <= .01 after Bonferroni correction. RESULTS: A
      positive association was detected between NSCL+/-P and SNP rs1530364 in the WNT9B
      gene. Haplotype analysis showed an association of WNT3 and WNT9B haplotypes. No
      association was detected between NSCL+/-P and individual SNPs in WNT3.
      CONCLUSION: Our study further supports the involvement of WNT9B as a cleft
      susceptibility gene in Brazilian families experiencing NSCL+/-P. Although
      additional studies are still necessary to unveil the exact mechanism by which WNT
      genes would contribute to NSCL+/-P, allelic polymorphisms in these genes and
      their interactions may partly explain the variance of individual susceptibility
      to NSCL+/-P.

PMID- 24437586
TI  - Do orofacial clefts represent different genetic entities?
AB  - OBJECTIVE: To contribute to the understanding of potential genetic differences
      between different cleft types. METHOD: Analysis of family history concerning
      cleft type and search for cleft-type-specific associations in candidate genes
      performed in 98 individuals from 98 families. RESULTS: In a given family, the
      cleft type of a second case was more often identical to the index case than
      expected by chance. Each type of cleft (cleft lip [CL], cleft lip and palate
      [CLP], cleft palate only [CP], and submucous cleft palate only [SMCP]) was
      associated with different genes. CONCLUSION: Family history indicates some
      specificity of cleft types. The observed phenotype-genotype associations were
      compatible with this interpretation in that significant associations occurred
      with disjoint sets of genes in each cleft type. These observations indicate that
      CL, CLP, CP, and SMCP might represent genetically different entities.

PMID- 24437587
TI  - Effects of nasal port area on perception of nasality and measures of nasalance
      based on computational modeling.
AB  - OBJECTIVE: This study examined the relation between nasal port area, nasalance,
      and perceptual ratings of nasality for three English corner vowels, /i/, /u/, and
      /a/. DESIGN: Samples were simulated using a computational model that allowed for
      exact control of nasal port size and direct measures of nasalance. Perceptual
      ratings were obtained using a paired stimulus presentation. PARTICIPANTS: Four
      experienced listeners. MAIN OUTCOME MEASURES: Nasalance and perceptual ratings of
      nasality. RESULTS: Findings show that perceptual ratings of nasality and
      nasalance increased for samples generated with nasal port areas up to and
      including 0.16 cm(2) but plateaued in samples generated with larger nasal port
      areas. No vowel differences were noted for perceptual ratings. CONCLUSIONS: This
      work extends previously published work by including nasal port areas
      representative of those reported in the literature for clinical populations.
      Continued work using samples with varied phonetic context and varying
      suprasegmental and temporal characteristics are needed.

PMID- 24437588
TI  - CBS c.844ins68 Polymorphism Frequencies in Control Populations: Implications on
      Nonsyndromic Cleft Lip With or Without Cleft Palate.
AB  - INTRODUCTION: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a
      common birth defect with substantial clinical and social impact. Folate
      deficiency is one of the factors that have been associated with increased risk
      for NSCLP. Polymorphisms in folate and homocysteine pathway genes may act as
      susceptibility factors. OBJECTIVE: The objective of this study was to evaluate
      prevalence estimates of cystathionine beta-synthase (CBS) insertion of 68-bp
      (c.844ins68) polymorphisms and their correlation with NSCLP. MATERIAL AND
      METHODS: A total of 236 unrelated individuals from seven Indian populations and
      an additional 355 cases with NSCLP and 357 controls without NSCLP were included
      in this study. We investigated the CBS c.844ins68 polymorphism in all samples.
      Genotyping was performed with polymerase chain reaction and electrophoresis. The
      data were statistically analyzed using the chi-square test. RESULTS: The CBS
      c.844ins68 allele is present in six of the seven populations analyzed, and allele
      frequencies range from 1.5% in Balija to 9.1% in Sugali populations. The CBS
      c.844ins68 polymorphism showed a significant protective effect on NSCLP at both
      genotype (WW versus WI: odds ratio [OR] = 0.54, 95% confidence interval [CI] =
      0.31 to 0.95, P = .149) and allele levels (W versus I: OR = 0.56, 95% CI = 0.32
      to 0.96, P = .033). CONCLUSIONS: The current study observed significant
      differences in the frequency of the CBS 844ins68 allele across populations. There
      is a significant association between CBS c.844ins68 polymorphism and cleft lip
      and palate in the Indian population. Additional studies are warranted to identify
      the functional variants in the genes controlling homocysteine as etiological
      contributors to the formation of oral clefts.

PMID- 24437592
TI  - [ZnBi4](3-) pentagon in K6ZnBi5: aromatic all-metal heterocycle.
AB  - The first aromatic all-metal heterocycle, [ZnBi4](3-), found in the metallic
      salt, K6ZnBi5, has been synthesized and structurally characterized. The exactly
      planar [ZnBi4](3-) pentagon with six pi electrons coupled with multiply bonded Zn
      Bi and Bi-Bi bonds, multicentered pi-conjugated bonding, and negative nucleus
      independent chemical shift values reveals its aromatic character. The metallic
      nature of K6ZnBi5 has been established by Pauli-type temperature-independent
      paramagnetism and theoretical analysis of the band structure and total/partial
      density of states. 

PMID- 24437593
TI  - Direct imine acylation for molecular diversity in heterocyclic synthesis.
AB  - Imines and carboxylic acids have been directly coupled using propylphosphonic
      acid anhydride and NEt(i-Pr)2 to give N-acyliminium ions, which were
      intramolecularly trapped with oxygen, nitrogen, sulfur, and carbon nucleophiles
      to provide a wide range of structurally diverse heterocycles.

PMID- 24437598
TI  - The limited role of the glomerular endothelial cell glycocalyx as a barrier to
      transglomerular albumin transport.
AB  - For over 50 years, the glomerular filter has been thought to exert an uniquely
      significant barrier to the transport of albumin. The glomerular endothelial cell
      glycocalyx is considered to contribute to this important barrier restriction. In
      renal disease, structural alterations to this layer have been associated with
      albuminuria. It appears however the claims of the influence of this barrier have
      been overstated. The behaviour of albumin in systems that model the glycocalyx
      has been studied widely and the results demonstrate that the endothelial
      glycocalyx would offer only relatively small effective barrier to albumin. This
      has been confirmed in studies on macromolecular exchange in non-renal capillary
      beds with similar endothelial glycocalyx. The experimental perturbations to the
      glomerular endothelial glycocalyx (through enzyme treatments, saline washouts)
      also create only relatively small changes in the level of albuminuria as compared
      to changes in albumin excretion seen in renal disease and nephrotic states.
      Additionally, it is questionable how specific these perturbations are. Overall,
      the endothelial glycocalyx most likely has biological functions like it does in
      other extracellular regions involving hydration through osmotic pressure and
      offering charge-mediated binding of various molecules. This confirms work by
      Comper and colleagues that the glomerular sieving of albumin is not unique and is
      consistent with that of size selectivity that results in significant amounts of
      albumin being filtered normally, retrieved by proximal tubules and returned to
      the blood supply.

PMID- 24437599
TI  - Lens capsule as a model to study type IV collagen.
AB  - The study of collagen IV has benefited greatly from the seminal work conducted by
      Arthur Veis and colleagues over three decades ago. Through a series of electron
      microscopy studies focused on lens basement membrane, an appreciation was gained
      for the distinct network-forming properties of collagen IV. Veis correctly
      suggested that network assembly is a phenomenon of the non-collagenous termini of
      the molecule. This review seeks to document how the field advanced following
      these seminal conclusions, including recent discoveries regarding the molecular
      reinforcement of networks that support Veis' conclusions.

PMID- 24437600
TI  - Normalization of the tumor microenvironment: evidence for tissue inhibitor of
      metalloproteinase-2 as a cancer therapeutic.
AB  - Matrix metalloproteinases (MMPs) are members of the Metzincin family of proteases
      responsible for degrading the extracellular matrix (ECM). In early studies, MMP
      degradation of the sub-epithelial basement membrane was thought to be tumor cell
      autonomous and contribute to the invasive behavior of malignant cells. It is now
      recognized that MMPs have multiple roles that can either promote or inhibit tumor
      progression and metastasis. The endogenous inhibitors of the MMPs are the tissue
      inhibitors of metalloproteinases (TIMPs). Early studies on the tumor
      microenvironment revealed TIMP function to be principally through the inhibition
      of MMPs, thereby blocking tumor cell migration and invasion. However, data from a
      number of laboratories are now reporting that TIMPs have direct cellular
      functions, independent of their MMP inhibitory activity. The TIMPs can modulate
      normal tissue physiology and development, as well as pathology and progression in
      a variety of acute and chronic disease states. In this review, we briefly
      describe the role of MMPs and TIMPs in ECM turnover and formation of the tumor
      microenvironment. Based on the evidence presented, we postulate that TIMP-2 and
      other soluble components of the normal ECM may provide a novel therapeutic
      approach to cancer treatment through "normalization" of the tumor
      microenvironment.

PMID- 24437601
TI  - Novel functions for type II procollagen.
AB  - Cartilage is unique in being established as an avascular tissue during
      development. Cartilage also has the property of being resistant to tumor invasion
      with tumors arising on the periphery of cartilage and in bone, but sparing the
      cartilage. These properties have been investigated for many years beginning in
      the 1970's. Many anti-angiogenic molecules have been isolated from cartilage in
      small amounts. Portions of molecules from cartilage also possess anti-angiogenic
      properties when released from the parent protein by degradative extracellular
      enzymes. This review highlights a new anti-angiogenic and anti-tumor moiety from
      cartilage, the NH2-propeptide of type IIB collagen. When released from the
      procollagen during synthesis, the propeptide has the capacity to act on its own
      to protect the cartilage by killing of endothelial cell, osteoclasts and tumor
      cells.

PMID- 24437602
TI  - Self-assembled monolayer facilitates epithelial-mesenchymal interactions
      mimicking odontogenesis.
AB  - Cell-cell interactions are vital for embryonic organ development and normal
      function of differentiated cells and tissues. In this study we have developed a
      self-assembled monolayer-based co-culture system to study tooth morphogenesis.
      Specifically, we designed a 2-D microenvironment present in the dental tissue by
      creating a well-structured, laterally organized epithelial and mesenchymal cell
      co-culture system by patterning the cell-attachment substrate. Chemical
      modifications were used to develop tunable surface patterns to facilitate
      epithelial-mesenchymal interactions mimicking the developing tooth. Such a design
      promoted interactions between monolayer's of the 2 cell types and provided
      signaling cues that resulted in cellular differentiation and mineralized matrix
      formation. Gene expression analysis showed that these co-cultures mimicked in
      vivo conditions than monolayer cultures of a single cell type.

PMID- 24437604
TI  - Sea urchins have teeth? A review of their microstructure, biomineralization,
      development and mechanical properties.
AB  - Sea urchins possess a set of five teeth which are self-sharpening and which
      continuously replace material lost through abrasion. The continuous replacement
      dictates that each tooth consists of the range of developmental states from
      discrete plates in the plumula, the least mineralized and least mature portion,
      to plates and needle-prisms separated by cellular syncytia at the beginning of
      the tooth shaft to a highly dense structure at the incisal end. The
      microstructures and their development are reviewed prior to a discussion of
      current understanding of the biomineralization processes operating during tooth
      formation. For example, the mature portions of each tooth consist of single
      crystal calcite but the early stages of mineral formation (e.g. solid amorphous
      calcium carbonate, ions in solution) continue to be investigated. The second
      stage mineral that cements the disparate plates and prisms together has a much
      higher Mg content than the first stage prisms and needles and allows the tooth to
      be self-sharpening. Mechanically, the urchin tooth's calcite performs better than
      inorganic calcite, and aspects of tooth functionality that are reviewed include
      the materials properties themselves and the role of the orientations of the
      plates and prisms relative to the axes of the applied loads. Although the
      properties and microarchitecture of sea urchin teeth or other mineralized tissues
      are often described as optimized, this view is inaccurate because these superb
      solutions to the problem of constructing functional structures are intermediaries
      not endpoints of evolution.

PMID- 24437603
TI  - The role of acidic phosphoproteins in biomineralization.
AB  - Biomineralization is the process by which living organisms deposit mineral in the
      extracellular matrix. In nature, almost 50% of biominerals are calcium-bearing
      minerals. In addition to calcium, we find biominerals formed from silica and
      magnetite. Calcium-containing biominerals could be either calcium phosphate as in
      apatite found in vertebrates or calcium carbonate as in calcite and aragonite
      found in many invertebrates. Since all biomineralization is matrix mediated, an
      understanding of the nature of the proteins involved is essential in elucidating
      its mechanism. This review will discuss some of the proteins involved in the
      process of biomineralization involving calcium. Two proteins, dentin matrix
      protein 1 and dentin phosphoprotein (Phosphophoryn) will serve as models for the
      vertebrate system, and two others - P16 and phosphodontin will serve as models
      for the invertebrate system.

PMID- 24437605
TI  - Direct microCT imaging of non-mineralized connective tissues at high resolution.
AB  - The 3D imaging of soft tissues in their native state is challenging, especially
      when high resolution is required. An X-ray-based microCT is, to date, the best
      choice for high resolution 3D imaging of soft tissues. However, since X-ray
      attenuation of soft tissues is very low, contrasting enhancement using different
      staining materials is needed. The staining procedure, which also usually involves
      tissue fixation, causes unwanted and to some extent unknown tissue alterations.
      Here, we demonstrate that a method that enables 3D imaging of soft tissues
      without fixing and staining using an X-ray-based bench-top microCT can be applied
      to a variety of different tissues. With the sample mounted in a custom-made
      loading device inside a humidity chamber, we obtained soft tissue contrast and
      generated 3D images of fresh, soft tissues with a resolution of 1 micron voxel
      size. We identified three critical conditions which make it possible to image
      soft tissues: humidified environment, mechanical stabilization of the sample and
      phase enhancement. We demonstrate the capability of the technique using different
      specimens: an intervertebral disc, the non-mineralized growth plate, stingray
      tessellated radials (calcified cartilage) and the collagenous network of the
      periodontal ligament. Since the scanned specimen is fresh an interesting
      advantage of this technique is the ability to scan a specimen under load and
      track the changes of the different structures. This method offers a unique
      opportunity for obtaining valuable insights into 3D structure-function
      relationships of soft tissues.

PMID- 24437609
TI  - Stable water isotope patterns in a climate change hotspot: the isotope hydrology
      framework of Corsica (western Mediterranean).
AB  - The Mediterranean is regarded as a region of intense climate change. To better
      understand future climate change, this area has been the target of several
      palaeoclimate studies which also studied stable isotope proxies that are directly
      linked to the stable isotope composition of water, such as tree rings, tooth
      enamel or speleothems. For such work, it is also essential to establish an
      isotope hydrology framework of the region of interest. Surface waters from
      streams and lakes as well as groundwater from springs on the island of Corsica
      were sampled between 2003 and 2009 for their oxygen and hydrogen isotope
      compositions. Isotope values from lake waters were enriched in heavier isotopes
      and define a local evaporation line (LEL). On the other hand, stream and spring
      waters reflect the isotope composition of local precipitation in the catchment.
      The intersection of the LEL and the linear fit of the spring and stream waters
      reflect the mean isotope composition of the annual precipitation (deltaP) with
      values of-8.6(+/- 0.2) 0/00 for delta(18)O and-58(+/- 2) 0/00 for delta(2)H. This
      value is also a good indicator of the average isotope composition of the local
      groundwater in the island. Surface water samples reflect the altitude isotope
      effect with a value of-0.17(+/- 0.02) 0/00 per 100 m elevation for oxygen
      isotopes. At Vizzavona Pass in central Corsica, water samples from two catchments
      within a lateral distance of only a few hundred metres showed unexpected but
      systematic differences in their stable isotope composition. At this specific
      location, the direction of exposure seems to be an important factor. The
      differences were likely caused by isotopic enrichment during recharge in warm
      weather conditions in south-exposed valley flanks compared to the opposite, north
      exposed valley flanks.

PMID- 24437612
TI  - Order, viscoelastic, and dielectric properties of symmetric and asymmetric
      alkyl[1]benzothieno[3,2-b][1]benzothiophenes.
AB  - The morphology, the viscoelastic, the dielectric properties and the dynamics of
      phase transformation are studied in symmetrically and asymmetrically substituted
      alkyl[1]benzothieno[3,2-b][1]benzothiophenes (C8-BTBT) by X-ray scattering,
      rheology, and dielectric spectroscopy. The interlayer spacing reflects the
      molecular and supramolecular ordering, respectively, in the symmetrically and
      asymmetrically substituted BTBTs. In the asymmetric BTBT, the core layer is
      double in size with a broader network of intermolecular interactions though the
      increased S-S contacts that is prerequisite for the development of high
      performance OFET devices. Two crystal states with elastic and viscoelastic
      responses were identified in the symmetric compound. In contrast, the SmA phase
      in the asymmetric compound is a viscoelastic solid. A path-dependent dielectric
      environment with a switchable dielectric permittivity was found in both compounds
      by cooling below 0  degrees C with possible implications to charge transport. The
      kinetics of phase transformation to the crystalline and SmA phases revealed a
      nucleation and growth mechanism with rates dominated by the low activation
      barriers. 

PMID- 24437606
TI  - LIBSA--a method for the determination of ligand-binding preference to allosteric
      sites on receptor ensembles.
AB  - Incorporation of receptor flexibility into computational drug discovery through
      the relaxed complex scheme is well suited for screening against a single binding
      site. In the absence of a known pocket or if there are multiple potential binding
      sites, it may be necessary to do docking against the entire surface of the target
      (global docking). However no suitable and easy-to-use tool is currently available
      to rank global docking results based on the preference of a ligand for a given
      binding site. We have developed a protocol, termed LIBSA for LIgand Binding
      Specificity Analysis, that analyzes multiple docked poses against a single or
      ensemble of receptor conformations and returns a metric for the relative binding
      to a specific region of interest. By using novel filtering algorithms and the
      signal-to-noise ratio (SNR), the relative ligand-binding frequency at different
      pockets can be calculated and compared quantitatively. Ligands can then be
      triaged by their tendency to bind to a site instead of ranking by affinity alone.
      The method thus facilitates screening libraries of ligand cores against a large
      library of receptor conformations without prior knowledge of specific pockets,
      which is especially useful to search for hits that selectively target a
      particular site. We demonstrate the utility of LIBSA by showing that it correctly
      identifies known ligand binding sites and predicts the relative preference of a
      set of related ligands for different pockets on the same receptor. 

PMID- 24437616
TI  - First site-specific incorporation of a noncanonical amino acid into the
      photosynthetic oxygen-evolving complex.
AB  - In photosystem II (PSII), water is oxidized at the oxygen-evolving complex. This
      process occurs through a light-induced cycle that produces oxygen and protons.
      While coupled proton and electron transfer reactions play an important role in
      PSII and other proteins, direct detection of internal proton transfer reactions
      is challenging. Here, we demonstrate that the unnatural amino acid, 7
      azatryptophan (7AW), has unique, pH-sensitive vibrational frequencies, which are
      sensitive markers of proton transfer. The intrinsically disordered, PSII subunit,
      PsbO, which contains a single W residue (Trp241), was engineered to contain 7AW
      at position 241. Fluorescence shows that 7AW-241 is buried in a hydrophobic
      environment. Reconstitution of 7AW(241)PsbO to PSII had no significant impact on
      oxygen evolution activity or flash-dependent protein dynamics. We conclude that
      directed substitution of 7AW into other structural domains is likely to provide a
      nonperturbative spectroscopic probe, which can be used to define internal proton
      pathways in PsbO. 

PMID- 24437617
TI  - Palladium catalyzed aryl(alkyl)thiolation of unactivated arenes.
AB  - A general palladium-catalyzed aryl(alkyl)thiolation of various substituted
      unactivated arenes is accomplished for the synthesis of diverse unsymmetrical
      diaryl(alkyl) sulfides in good yield employing electrophilic sulfur reagent 6
      derived from succinimide. The developed strategy was coupled with intramolecular
      arylation of a C-H bond to afford dibenzothiphene derivatives, an important
      moiety in material science as organic semiconductors. 

PMID- 24437620
TI  - Primary and secondary photodynamics of the violet/orange dual-cysteine NpF2164g3
      cyanobacteriochrome domain from Nostoc punctiforme.
AB  - Cyanobacteriochromes (CBCRs) are cyanobacterial photoreceptors distantly related
      to phytochromes. Like phytochromes, CBCRs photointerconvert between two
      photostates that accompany photoisomerization of their bilin chromophores. While
      phytochromes typically exhibit red/far-red photocycles, CBCR photocycles are much
      more diverse, spanning the near-ultraviolet and the entire visible region. All
      CBCRs described to date have a conserved Cys residue covalently attached to the
      linear tetrapyrrole (bilin) chromophore; two CBCR subfamilies also exploit a
      second thioether linkage to the chromophore for detection of near-ultraviolet to
      blue light. Here, we present the photodynamic analysis of the insert-Cys CBCR
      NpF2164g3, a representative of the second class of two-cysteine CBCRs. Using
      broadband transient absorption pump-probe spectroscopy, we characterize the
      primary (100 fs to 10 ns) and secondary (10 ns to 1 ms) photodynamics in both
      directions, examining photodynamics over nine decades of time. Primary
      isomerization dynamics occur on a ~10 ps time scale for both forward and reverse
      reactions. In contrast to previous studies on Tlr0924, a representative of the
      other class of two-cysteine CBCRs, formation and elimination of the second
      linkage are slower than the 1 ms experimental range probed here. These results
      extend our understanding of dual-cysteine CBCR photocycles in the phytochrome
      superfamily.

PMID- 24437625
TI  - A computational study: reactivity difference between phosphine- and amine
      catalyzed cycloadditions of allenoates and enones.
AB  - Allenoates and enones form cyclopentenes via a phosphine-catalyzed [3 + 2]
      cycloaddition while the amine-catalyzed [2 + 4] cycloaddition yields
      dihydropyrans or pyrans. The difference between these catalysts is studied with
      M06-2X/6-31+G* calculations. The addition of the catalyst to the allenoate is the
      first step in both pathways followed by the reaction with the enone. The
      formation of the [3 + 2] phosphorus-ylide is exergonic, and hence, the [3 + 2]
      cycloaddition is kinetically favored over the [2 + 4] addition. Amines do not
      stabilize [3 + 2] ammonium-ylides. However, electron-withdrawing groups on the
      enone enable [2 + 4] cycloadditions. The strength of the electron-withdrawing
      group further controls the alpha/gamma regioselectivity of the [2 + 4]
      cycloaddition, and the analysis of the HOMO-LUMO interactions explains why only E
      dihydropyrans from the direct gamma-[2 + 4] cycloaddition have been observed in
      experiments. The quantum calculations further reveal a new path to the alpha-[2 +
      4] product starting with an intermediate Rauhut-Currier reaction. This new path
      is kinetically favored over the direct amine-catalyzed alpha-[2 + 4]
      cycloaddition. 

PMID- 24437626
TI  - Immune-mediated inflammatory reactions and tumors as skin side effects of
      inflammatory bowel disease therapy.
AB  - All drugs currently used for treating patients with inflammatory bowel disease
      (IBD - including Crohn's disease and ulcerative colitis) have the potential to
      induce skin lesions ranging from mild eruptions to more serious and widespread
      clinical presentations. The number of cutaneous adverse reactions due to IBD
      therapies is progressively increasing and the most frequently involved drugs are
      thiopurines and biologics like tumor necrosis factor (TNF)-alpha antagonists. The
      main drug-induced cutaneous manifestations are non-melanoma skin cancer (NMSC),
      notably basal cell and squamous cell carcinomas, and viral skin infections for
      thiopurines and psoriasiform, eczematoid and lichenoid eruptions as well as skin
      infections and cutaneous lupus erythematosus for biologics. Cutaneous
      manifestations should be promptly recognized and correctly diagnosed in order to
      quickly establish an adequate therapy. The main treatment for NMSC is surgical
      excision whereas the management of immune-mediated inflammatory skin reactions
      varies from topical therapy for mild presentations to the shift to another drug
      alone or in combination with corticosteroids for extensive eruptions.

PMID- 24437629
TI  - Kinetic and mechanistic studies on the reaction of the vitamin B12 complex
      aquacobalamin with the HNO donor Angeli's salt: Angeli's salt and HNO react with
      aquacobalamin.
AB  - We report the first studies on the reaction between an HNO donor compound and
      vitamin B12 complexes. Kinetic and mechanistic studies have been carried out on
      the reaction between the vitamin B12 derivative aquacobalamin (H2OCbl(+)/HOCbl;
      pKa = 7.8) and the HNO donor Angeli's salt. Studies were carried out with
      aquacobalamin in excess, since nitrite also reacts with aquacobalamin to form
      nitrocobalamin (NO2Cbl). At pH <9.90 aquacobalamin reacts directly with the
      monoprotonated form of Angeli's salt, HN2O3(-), to form nitroxylcobalamin (NO(-)
      Cbl(III); NOCbl) and nitrite. At pH >10.80 the reaction instead switches
      predominantly to a mechanism in which spontaneous decomposition of Angeli's salt
      to give HNO and nitrite becomes the rate-determining step, followed by the rapid
      reaction between aquacobalamin and HNO/NO(-) to again give NOCbl. Both reactions
      proceed with a 1:1 stoichiometry and formation of nitrite is confirmed using the
      Griess assay. 

PMID- 24437630
TI  - Template CoMFA: the 3D-QSAR Grail?
AB  - Template CoMFA, a novel alignment methodology for training or test set structures
      in 3D-QSAR, is introduced. Its two most significant advantages are its complete
      automation and its ability to derive a single combined model from multiple
      structural series affecting a biological target. Its only two inputs are one or
      more "template" structures having 3D coordinates that share some Cartesian space,
      as may result from X-ray crystallography or pharmacophoric hypothesis, and one or
      more connectivity-only SAR tables associated with a common target. Template CoMFA
      also overcomes the major disadvantages of both existing 3D-QSAR alignment
      methodologies, specifically the tedium and subjectivity of familiar ad hoc
      approaches, and the awkwardness, occasional physicochemical heresies, and
      structural scope limitations of the purely topomer approach. The template CoMFA
      algorithms are described, and two of its application classes are presented. The
      first class, general models of binding to factor Xa and P38 map kinase, uses
      crystallographic structures as templates, with the encouraging result that the
      statistical qualities of each of these two combined models are equivalent to
      those of their constituent individual series models. The second, 15 data sets
      originally collected for validation of topomer CoMFA, with arbitrary structures
      as templates, confirms that the modeling power of template CoMFA resembles that
      of its predecessors. 

PMID- 24437633
TI  - Dermal decontamination for corrosive exposures.

PMID- 24437637
TI  - Self-assembly of an aspartate-rich sequence from the adenovirus fiber shaft:
      insights from molecular dynamics simulations and experiments.
AB  - The self-assembly of short peptides into fibrous nanostructures (such as fibrils
      and tubes) has recently become the subject of intense theoretical and
      experimental scrutiny, as such assemblies are promising candidates for
      nanobiotechnological applications. The sequences of natural fibrous proteins may
      provide a rich source of inspiration for the design of such short self-assembling
      peptides. We describe the self-assembly of the aspartate-rich undecapeptide
      (NH3(+)-LSGSDSDTLTV-NH2), a sequence derived from the shaft of the adenovirus
      fiber. We demonstrate that the peptide assembles experimentally into amyloid-type
      fibrils according to widely accepted diagnostic criteria. In addition, we
      investigate an aqueous solution of undecapeptides by molecular dynamics
      simulations with an implicit (GB) solvent model. The peptides are frequently
      arranged in intermolecular beta-sheets, in line with their amyloidogenic
      propensity. On the basis of both experimental and theoretical insights, we
      suggest possible structural models of the fibrils and their potential use as
      scaffolds for templating of inorganic materials. 

PMID- 24437638
TI  - Association of signaling transducers and activators of transcription 1 and
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is complex autoimmune disease which involves
      various facets of the immune system. Signaling transducers and activators of
      transcription 1 (STAT1) belongs to the family of STAT transcription factors that
      mediate various biological responses. Recently, studies in both experimental
      animal models of lupus and patients with SLE have revealed expression and
      activation of STAT1 is closely associated with the pathogenesis of SLE. Moreover,
      increased production of interferons (IFNs) and aberrant activation of IFNs
      signaling, which is mechanistically linked to increased level of STAT1, are
      crucial for the development of SLE. Therefore, we will focus on the association
      of STAT1 and SLE based on recent understandings to render more information about
      the mechanisms of STAT1 might perform in. Hopefully, the information obtained
      will lead to a better understanding of the development and pathogenesis of
      systemic autoimmune diseases, as well as its clinical implications and
      therapeutic potential.

PMID- 24437639
TI  - Magnetic circular dichroism and electronic structure of [Re2X4(PMe3)4]+ (X = Cl,
      Br).
AB  - Magnetic circular dichroism (MCD) and electronic absorption spectroscopies have
      been used to probe the electronic structure of the classical paramagnetic metal
      metal-bonded complexes [Re2X4(PMe3)4](+) (X = Cl, Br). A violation of the MCD sum
      rule is observed that indicates the presence of ground-state contributions to the
      MCD intensity. The z-polarized delta -> delta* band in the near-IR is formally
      forbidden in MCD but gains intensity through a combination of ground- and excited
      state mechanisms to yield a positive C term. 

PMID- 24437641
TI  - Synthesis of tunable diamine ligands with spiro indane-2,2'-pyrrolidine backbone
      and their applications in enantioselective Henry reaction.
AB  - Novel diamine ligands with spiro indane-2,2'-pyrrolidine scaffold were
      synthesized starting from Seebach's oxazolidinone 6 and were subsequently
      employed in asymmetric Henry reaction. Following the initial experimental
      findings, further synthesis resulted in two types of spiro diamines, with varying
      substituents at both nitrogen atoms. Ligands of type A, containing a small
      substituent at N-1' atom, and a large group at N-1 atom gave predominantly the S
      configured beta-nitroalcohol, while ligands of type B, with the reversed location
      of small and large substituents furnished the R-configured product. Both types of
      ligands turned out to be versatile catalysts for the Henry reaction between
      nitromethane and an assortment of aryl as well as alkyl aldehydes offering either
      S- (lig. A) or R-configured (lig. B) nitroalcohols in a good to high chemical
      yield and an excellent enantioselectivity up to 99% ee.

PMID- 24437644
TI  - Radon survey and soil gamma doses in primary schools of Batman, Turkey.
AB  - A survey was conducted to evaluate levels of indoor radon and gamma doses in 42
      primary schools located in Batman, southeastern Anatolia, Turkey. Indoor radon
      measurements were carried out using CR-39 solid-state nuclear track detector
      based radon dosimeters. The overall mean annual (222)Rn activity in the surveyed
      area was found to be 49 Bq m(-3) (equivalent to an annual effective dose of 0.25
      mSv). However, in one of the districts (Besiri) the maximum radon value turned
      out to be 307 Bq m(-3). The estimated annual effective doses are less than the
      recommended action level (3-10 mSv). It is found that the radon concentration
      decreases with increasing floor number. The concentrations of natural and
      artificial radioisotopes were determined using gamma-ray spectroscopy for soil
      samples collected in close vicinity of the studied schools. The mean gamma
      activity concentrations in the soil samples were 31, 25, 329 and 12 Bq kg(-1) for
      (226)Ra, (232)Th, (40)K and (137)Cs, respectively. The radiological parameters
      such as the absorbed dose rate in air and the annual effective dose equivalent
      were calculated. These radiological parameters were evaluated and compared with
      the internationally recommended values.

PMID- 24437648
TI  - Facile assembly of chiral tetrahydrothiopyrans containing four consecutive
      stereocenters via an organocatalytic enantioselective Michael-Michael cascade.
AB  - An organocatalytic enantioselective Michael-Michael cascade reaction has been
      implemented for the creation of structurally variant chiral tetrahydrothiopyrans.
      The process is realized by employment of new bifunctional ketothioether enones
      and proceeds highly enantioselectively with formation of four consecutive
      stereogenic centers. 

PMID- 24437653
TI  - Tetranuclear hetero-metal [Co(II)2Ln(III)2] (Ln = Gd, Tb, Dy, Ho, La) complexes
      involving carboxylato bridges in a rare MU4-eta(2):eta(2) mode: synthesis,
      crystal structures, and magnetic properties.
AB  - A new family of 3d-4f heterometal 2 * 2 complexes
      [Co(II)2(L)2(PhCOO)2Ln(III)2(hfac)4] (1-5) (Ln = Gd (compound 1), Tb (compound
      2), Dy (compound 3), Ho (compound 4), and La (compound 5)) have been synthesized
      in moderate yields (48-63%) following a single-pot protocol using stoichiometric
      amounts (1:1 mol ratio) of [Co(II)(H2L)(PhCOO)2] (H2L = N,N'-dimethyl-N,N'-bis(2
      hydroxy-3,5-dimethylbenzyl)ethylenediamine) as a metalloligand and
      [Ln(III)(hfac)3(H2O)2] (Hhfac = hexafluoroacetylacetone) as a lanthanide
      precursor compound. Also reported with this series is the Zn-Dy analog
      [Zn(II)2(L)2(PhCOO)2Dy(III)2(hfac)4] 6 to help us in understanding the magnetic
      properties of these compounds. The compounds 1-6 are isostructural. Both
      hexafluoroacetylacetonate and benzoate play crucial roles in these structures as
      coligands in generating a tetranuclear core of high thermodynamic stability
      through a self-assembly process. The metal centers are arranged alternately at
      the four corners of this rhombic core, and the carboxylato oxygen atoms of each
      benzoate moiety bind all of the four metal centers of this core in a rare MU4
      eta(2):eta(2) bridging mode as confirmed by X-ray crystallography. The magnetic
      susceptibility and magnetization data confirm a paramagnetic behavior, and no
      remnant magnetization exists in any of these compounds at vanishing magnetic
      field. The metal centers are coupled in an antiferromagnetic manner in these
      compounds. The [Co(II)2Dy(III)2] compound exhibits a slow magnetic relaxation
      below 6 K, as proven by the AC susceptibility measurements; the activation energy
      reads U/kB = 8.8 K (tau0 = 2.0 * 10(-7) s) at BDC = 0, and U/kB = 7.8 K (tau0 =
      3.9 * 10(-7) s) at BDC = 0.1 T. The [Zn(II)2Dy(III)2] compound also behaves as a
      single-molecule magnet with U/kB = 47.9 K and tau0 = 2.75 * 10(-7) s. 

PMID- 24437652
TI  - Nuclear hyperfine and quadrupole tensor characterization of the nitrogen hydrogen
      bond donors to the semiquinone of the QB site in bacterial reaction centers: a
      combined X- and S-band (14,15)N ESEEM and DFT study.
AB  - The secondary quinone anion radical QB(-) (SQB) in reaction centers of
      Rhodobacter sphaeroides interacts with Ndelta of His-L190 and Np (peptide
      nitrogen) of Gly-L225 involved in hydrogen bonds to the QB carbonyls. In this
      work, S-band (~3.6 GHz) ESEEM was used with the aim of obtaining a complete
      characterization of the nuclear quadrupole interaction (nqi) tensors for both
      nitrogens by approaching the cancelation condition between the isotropic
      hyperfine coupling and (14)N Zeeman frequency at lower microwave frequencies than
      traditional X-band (9.5 GHz). By performing measurements at S-band, we found a
      dominating contribution of Ndelta in the form of a zero-field nqi triplet at
      0.55, 0.92, and 1.47 MHz, defining the quadrupole coupling constant K = e(2)qQ/4h
      = 0.4 MHz and associated asymmetry parameter eta = 0.69. Estimates of the
      hyperfine interaction (hfi) tensors for Ndelta and Np were obtained from
      simulations of 1D and 2D (14,15)N X-band and three-pulse (14)N S-band spectra
      with all nuclear tensors defined in the SQB g-tensor coordinate system. From
      simulations, we conclude that the contribution of Np to the S-band spectrum is
      suppressed by its strong nqi and weak isotropic hfi comparable to the level of
      hyperfine anisotropy, despite the near-cancelation condition for Np at S-band.
      The excellent agreement between our EPR simulations and DFT calculations of the
      nitrogen hfi and nqi tensors to SQB is promising for the future application of
      powder ESEEM to full tensor characterizations. 

PMID- 24437656
TI  - How can more women-owned technology businesses get funding?

PMID- 24437661
TI  - Binding characteristics of sodium saccharin with calf thymus DNA in vitro.
AB  - The binding characteristics of sodium saccharin (SSA), an artificial sweetener,
      with calf thymus DNA (ctDNA) were investigated by multispectroscopic techniques,
      chemometrics, and molecular simulation. A combined fluorescence and UV-vis
      spectroscopic data matrix was resolved by the multivariate curve resolution
      alternating least-squares (MCR-ALS) chemometrics algorithm. The MCR-ALS analysis
      extracted simultaneously the concentration profiles and spectra for the three
      components (SSA, ctDNA, and SSA-ctDNA complex) to quantitatively monitor the SSA
      ctDNA interaction, which is difficult to perform by conventional spectroscopic
      approach. The binding mode of SSA to ctDNA was principally through groove binding
      as revealed by ctDNA melting temperature studies, viscosity measurements, and
      iodide and salt quenching effects. Analysis of the Fourier transform infrared and
      circular dichroism spectra as well as molecular docking indicated that SSA
      preferentially bound to the guanine base of ctDNA and led to a transformation
      from B-like DNA structure to A-like conformation. Moreover, gel electrophoresis
      results suggested that SSA did not induce any significant cleavage in plasmid
      DNA. 

PMID- 24437662
TI  - Asymmetry of single cells and where that leads.
AB  - Most single animal cells have an internal vector that determines where recycling
      membrane is added to the cell's surface. Because of the specific molecular
      composition of this added membrane, a dynamic asymmetry is formed on the surface
      of the cell. The consequences of this dynamic asymmetry are discussed, together
      with what they imply for how cells move. The polarity of a single-celled embryo,
      such as that of the nematode Caenorhabditis elegans, is explored in a similar
      framework. 

PMID- 24437663
TI  - Journeys in science: glycobiology and other paths.
AB  - My scientific journeys began at Oxford nearly 50 years ago. My paths have taken
      me from magnetic resonance through enzyme systems to antibodies, which led
      directly to glycobiology. Oxford University's first industrial grant helped the
      development of the technology for isolating and sequencing oligosaccharides from
      glycoproteins. This technology was disseminated through a spin-off company,
      Oxford GlycoSystems, and by the establishment of the Glycobiology Institute. The
      technology gave rise to the concept of glycoforms, which allow diversification of
      a protein's properties. Iminosugars, which are glucosidase inhibitors, can
      interfere with the initial steps of glycan processing on proteins and inhibit
      three-dimensional folding of glycoproteins. Glucosidase targets for therapy
      include viral envelope glycoproteins. Clinical trials of an iminosugar as an
      antiviral for dengue virus are under way. Another iminosugar activity, inhibition
      of glycolipid synthesis, resulted in a drug for Gaucher disease, which was
      approved worldwide in 2002. The success of the company and the institute allowed
      me to undertake several initiatives, in the United Kingdom and abroad, that might
      help the paths of future generations of scientists. 

PMID- 24437665
TI  - General subpopulation framework and taming the conflict inside populations.
AB  - Structured evolutionary algorithms have been investigated for some time. However,
      they have been under explored especially in the field of multi-objective
      optimization. Despite good results, the use of complex dynamics and structures
      keep the understanding and adoption rate of structured evolutionary algorithms
      low. Here, we propose a general subpopulation framework that has the capability
      of integrating optimization algorithms without restrictions as well as aiding the
      design of structured algorithms. The proposed framework is capable of
      generalizing most of the structured evolutionary algorithms, such as cellular
      algorithms, island models, spatial predator-prey, and restricted mating based
      algorithms. Moreover, we propose two algorithms based on the general
      subpopulation framework, demonstrating that with the simple addition of a number
      of single-objective differential evolution algorithms for each objective, the
      results improve greatly, even when the combined algorithms behave poorly when
      evaluated alone at the tests. Most importantly, the comparison between the
      subpopulation algorithms and their related panmictic algorithms suggests that the
      competition between different strategies inside one population can have
      deleterious consequences for an algorithm and reveals a strong benefit of using
      the subpopulation framework. 

PMID- 24437666
TI  - An adaptive multi-swarm optimizer for dynamic optimization problems.
AB  - The multipopulation method has been widely used to solve dynamic optimization
      problems (DOPs) with the aim of maintaining multiple populations on different
      peaks to locate and track multiple changing optima simultaneously. However, to
      make this approach effective for solving DOPs, two challenging issues need to be
      addressed. They are how to adapt the number of populations to changes and how to
      adaptively maintain the population diversity in a situation where changes are
      complicated or hard to detect or predict. Tracking the changing global optimum in
      dynamic environments is difficult because we cannot know when and where changes
      occur and what the characteristics of changes would be. Therefore, it is
      necessary to take these challenging issues into account in designing such
      adaptive algorithms. To address the issues when multipopulation methods are
      applied for solving DOPs, this paper proposes an adaptive multi-swarm algorithm,
      where the populations are enabled to be adaptive in dynamic environments without
      change detection. An experimental study is conducted based on the moving peaks
      problem to investigate the behavior of the proposed method. The performance of
      the proposed algorithm is also compared with a set of algorithms that are based
      on multipopulation methods from different research areas in the literature of
      evolutionary computation. 

PMID- 24437667
TI  - Using stable isotopes and major ions to identify hydrological processes and
      geochemical characteristics in a typical karstic basin, Guizhou, Southwest China.
AB  - The investigation of hydrological processes is very important for water resource
      development in karst basins. In order to understand these processes associated
      with complex hydrogeochemical evolution, a typical basin was chosen in Houzai,
      southwest China. The basin was hydrogeologically classified into three zones
      based on hydrogen and oxygen isotopes as well as the field surveys. Isotopic
      values were found to be enriched in zone 2 where paddy fields were prevailing
      with well-developed underground flow systems, and heavier than those in zone 1.
      Zone 3 was considered as the mixture of zones 1 and 2 with isotopic values
      falling in the range between the two zones. A conceptual hydrological model was
      thus proposed to reveal the probable hydrological cycle in the basin. In
      addition, major processes of long-term chemical weathering in the karstic basin
      were discussed, and reactions between water and carbonate rocks proved to be the
      main geochemical processes in karst aquifers. 

PMID- 24437668
TI  - Tandem sp3 C-H functionlization/decarboxylation of 2-alkylazaarenes with coumarin
      3-carboxylic acids.
AB  - The catalyst-free sp(3) C-H functionalization of 2-alkylazaarenes has been
      achieved in the reaction with (thio)coumarin-3-carboxylic acids. Followed by a
      tandem decarboxylation, this method provides facile synthesis of biologically
      important azaarene-substituted 3,4-dihydro(thio)coumarins in a single step in
      high yields. 

PMID- 24437676
TI  - Classification of hepatotoxicants using HepG2 cells: A proof of principle study.
AB  - With the number of new drug candidates increasing every year, there is a need for
      high-throughput human toxicity screenings. As the liver is the most important
      organ in drug metabolism and thus capable of generating relatively high levels of
      toxic metabolites, it is important to find a reliable strategy to screen for drug
      induced hepatotoxicity. Microarray-based transcriptomics is a well-established
      technique in toxicogenomics research and is an ideal approach to screen for drug
      induced injury at an early stage. The aim of this study was to prove the
      principle of classifying known hepatotoxicants and nonhepatotoxicants using their
      distinctive gene expression profiles in vitro in HepG2 cells. Furthermore, we
      undertook to subclassify the hepatotoxic compounds by investigating the subclass
      of cholestatic compounds. Prediction analysis for microarrays was used for
      classification of hepatotoxicants and nonhepatotoxicants, which resulted in an
      accuracy of 92% on the training set and 91% on the validation set, using 36
      genes. A second model was set up with the goal of finding classifiers for
      cholestasis, resulting in 12 genes that appeared capable of correctly classifying
      8 of the 9 cholestatic compounds, resulting in an accuracy of 93%. We were able
      to prove the principle that transcriptomic analyses of HepG2 cells can indeed be
      used to classify chemical entities for hepatotoxicity. Genes selected for
      classification of hepatotoxicity and cholestasis indicate that endoplasmic
      reticulum stress and the unfolded protein response may be important cellular
      effects of drug-induced liver injury. However, the number of compounds in both
      the training set and the validation set should be increased to improve the
      reliability of the prediction.

PMID- 24437677
TI  - Structural, spectral, and electrochemical properties of nickel(II), copper(II),
      and zinc(II) complexes containing 12-membered pyridine- and pyridol-based tetra
      aza macrocycles.
AB  - The structural, electronic, and electrochemical properties of a series of novel
      12-membered pyridine- and pyridol-based tetra-aza transition-metal (Ni, Cu, Zn)
      complexes {[M(II)(L1)Cl](ClO4), [M(II)(L2)Cl](ClO4), and [M(II)(L3)Cl](ClO4)} are
      described (L1 (Pyclen) = 1,4,7,10-tetra-aza-2,6-pyridinophane; L2 = 3,6,9,15
      tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol; L3 = 3,6,9,15-tetra
      azabicyclo[9.3.1]penta-deca- 1(15),11,13-trien-12-ol). The subtle variations in
      the chemical properties of these complexes were investigated using X-ray
      crystallography, UV-vis and NMR spectroscopy, and cyclic voltammetry. In the
      solid-state, the Ni(II) complexes adopt a unique bimetallic and cis-octahedral
      (MU-Cl)2 coordination sphere, and the electronic studies provide further evidence
      for the existence of a six-coordinate Ni(II) species in solution. The pyridol
      based Cu(II) and Zn(II) complexes contain five-coordinate (N4Cl) geometries in
      the solid-state, in which the four N-donor atoms are not coplanar. Hydroxylation
      of the pyridine ring was found to increase the amount of pi electronic charge
      density residing throughout the aromatic system of the ligand backbone, increase
      the strength of the M-Cl and M-N (pyridine) basal x- and y-plane interactions,
      and decrease the axial M-N bonding interaction. The electrochemical studies
      demonstrate that (i) the Lewis-acidity of the metal center systematically
      decreases across the series {[Cu(II)(L3)Cl](ClO4) > [Cu(II)(L1)Cl](ClO4) >
      [Cu(II)(L2)Cl](ClO4)}, and (ii) the aromatic backbones allow access to both Cu(I)
      and Cu(III) species in solution. Overall, the experimental findings are
      consistent with the idea that p-hydroxylation enhances the Lewis-basicity of
      pyridine-based macrocycle and decreases the Lewis-acidity of the metal-ion, while
      m-hydroxylation decreases the electron-donating ability of the backbone and
      increases the metal-ion Lewis-acidity. 

PMID- 24437678
TI  - High-energy chemistry of formamide: a simpler way for nucleobase formation.
AB  - The formation of nucleobases from formamide during a high-energy density event,
      i.e., the impact of an extraterrestrial body into the planetary atmosphere, was
      studied by irradiation of formamide ice and liquid samples with a high-power
      laser in the presence of potential catalysts. FTIR spectroscopy, time-resolved
      emission spectroscopy, and GC-MS were subsequently used to monitor the
      dissociation of this molecule into stable molecular fragments (HCN, H2O, HNCO,
      H2, CO, and NH3) and unstable species (HNC, *CN, and *NH). The kinetic and
      thermodynamic models of the high-energy density event molecular dynamics have
      been suggested together with the reaction routes leading from the dissociation
      products to the nucleobases. In addition, using theoretical calculations, we
      propose a simple new reaction pathway for the formation of both pyrimidine and
      purine nucleobases involving *CN radical chemistry. 

PMID- 24437683
TI  - Stabilization of a cobalt-cobalt bond by two cyclic alkyl amino carbenes.
AB  - (Me2-cAAC:)2Co2 (2, where Me2-cAAC: = cyclic alkyl amino carbene, :C(CH2)(CMe2)2N
      2,6-iPr2C6H3)) was synthesized via the reduction of precursor (Me2-cAAC:Co(II)(MU
      Cl)Cl)2 (1) with KC8. 2 contains two cobalt atoms in the formal oxidation state
      zero. Magnetic measurement revealed that 2 has a singlet spin ground state S = 0.
      The cyclic voltammogram of 2 exhibits both one-electron oxidation and reduction,
      indicating the possible synthesis of stable species containing 2(*-) and 2(*+)
      ions. The latter was synthesized via reduction of 1 with required equivalents of
      KC8 and characterized as [(Me2-cAAC:)2Co2](*+)OTf(-) (2(*+)OTf(-)). Electron
      paramagnetic resonance spectroscopy of 2(*+) reveals the coupling of the electron
      spin with 2 equiv (59)Co isotopes, leading to a (Co(0.5))2 state. The
      experimental Co1-Co2 bond distances are 2.6550(6) and 2.4610(6) A for 2 and
      2(*+)OTf(-), respectively. Theoretical investigation revealed that both 2 and
      2(*+)OTf(-) possess a Co-Co bond with an average value of 2.585 A. A slight
      increase of the Co-Co bond length in 2 is more likely to be caused by the strong
      pi-accepting property of cAAC. 2(*+) is only 0.8 kcal/mol higher in energy than
      the energy minimum. The shortening of the Co-Co bond of 2(*+) is caused by
      intermolecular interactions. 

PMID- 24437685
TI  - Kinetics and mechanism of water cluster equilibria.
AB  - We combine hybrid density functional and transition state theory to investigate
      dynamical and mechanistic features of important aggregation, isomerization, and
      exchange pathways for cluster constituents of liquid water, building on the
      general concepts of quantum cluster equilibrium (QCE) theory. Such calculations
      confirm the extreme dynamical volatility of leading water cluster structural
      motifs, consistent with known ultrafast relaxation properties of liquid water and
      contrary to the superficial static imagery often associated with thermodynamic
      level description. We identify low-barrier mechanistic pathways and associated
      donor-acceptor orbital interactions that lead to facile scrambling of covalent
      and H-bond cluster motifs with remarkably small energetic barriers, significantly
      less than required to break even a single covalent or H-bond in isolation. 

PMID- 24437686
TI  - Antioxidant role of hydroxytyrosol on oxidative stress in cadmium-intoxicated
      rats: different effect in spleen and testes.
AB  - Hydroxytyrosol (2-(3,4dihydroxyphenyl)ethanol, (DPE), a phenolic compound present
      in olive oil, is known to have antioxidant properties. The aim of this study was
      to investigate the effect of DPE on oxidative stress induced by cadmium
      injections (CdCl2 2.5 mg/kg body weight) in spleen and testes of adult male rats.
      Oxidative stress was evaluated by measuring lipid peroxidation by thiobarbituric
      acid reactive substances (TBARS) as well as superoxide dismutase (SOD) and
      catalase (CAT) activities in cytosol and mitochondria. We found that in spleen no
      TBARS formation was detected following CdCl2 injections; however, DPE induces
      decrease in TBARS level in treated and untreated rats. On the contrary, we
      observed that DPE showed no effect on cadmium-induced lipid peroxidation in
      testes. Cytosolic activities of SOD and CAT decreased significantly only in
      spleen, where DPE restores the values to the control levels. Noteworthy,
      mitochondrial activities of SOD and CAT were strongly reduced by cadmium
      treatment both in spleen and testes, and DPE was not be able to restore their
      activity. Overall, the results from this study indicated that the DPE has
      different antioxidant efficiency in spleen and testis of cadmium intoxicated
      rats.

PMID- 24437687
TI  - New developments on the role of intramuscular connective tissue in meat
      toughness.
AB  - Intramuscular connective tissue (IMCT) forms a series of continuous networks
      integrating muscle fibers and fascicles into a whole organ. The contributions of
      IMCT to cooked meat toughness have long been recognized. This review concentrates
      on (a) the potential to manipulate IMCT in the growing animal, (b) postmortem
      effects on structure and properties of IMCT, and (c) developments in techniques
      to quantify IMCT in meat. A new hypothesis can explain why IMCT is enzymatically
      degraded in postmortem aging; however, after cooking, no differences are seen in
      the IMCT contribution to toughness. This hypothesis proposes that heat-insoluble
      collagen occurs in a weak pool and a strong pool, where the weak pool is most
      easily degraded by both proteolysis and heat. Far from being a constant
      background feature, the IMCT contribution to cooked meat toughness can be varied
      and deserves fresh research on how to achieve this. 

PMID- 24437688
TI  - Synthesis of functionalized polycyclic aromatic compounds via a formal [2 + 2]
      cycloaddition.
AB  - A base-promoted formal [2 + 2]-cycloaddition of 2-acyl-2'-vinyl-1,1'-biaryls was
      developed to provide polycyclic cyclobutanols as a step toward the synthesis of
      substituted polycyclic aromatic hydrocarbons and their heterocyclic analogues. 

PMID- 24437689
TI  - Hepatitis C virus NS5A replication complex inhibitors. Part 6: Discovery of a
      novel and highly potent biarylimidazole chemotype with inhibitory activity toward
      genotypes 1a and 1b replicons.
AB  - A medicinal chemistry campaign that was conducted to address a potential
      genotoxic liability associated with an aniline-derived scaffold in a series of
      HCV NS5A inhibitors with dual GT-1a/-1b inhibitory activity is described.
      Anilides 3b and 3c were used as vehicles to explore structural modifications that
      retained antiviral potency while removing the potential for metabolism-based
      unmasking of the embedded aniline. This effort resulted in the discovery of a
      highly potent biarylimidazole chemotype that established a potency benchmark in
      replicon assays, particularly toward HCV GT-1a, a strain with significant
      clinical importance. Securing potent GT-1a activity in a chemotype class lacking
      overt structural liabilities was a critical milestone in the effort to realize
      the full clinical potential of targeting the HCV NS5A protein. 

PMID- 24437695
TI  - Electrogenerated chemiluminescence peptide-based biosensor for the determination
      of prostate-specific antigen based on target-induced cleavage of peptide.
AB  - A novel electrogenerated chemiluminescence peptide-based biosensor (ECL-PB) for
      the determination of prostate-specific antigen (PSA) was developed on the basis
      of target-induced cleavage of a specific peptide within Nafion film incorporated
      with gold nanoparticles (AuNPs) and ECL emitting species. A specific peptide
      (CHSSKLQK) was used as a molecular recognition element; tris(2,2'-ripyridine)
      dichlororuthenium(II) (Ru(bpy)3(2+)) was used as ECL emitting species, and
      ferrocene carboxylic acid (Fc) was employed as ECL quencher. The ECL-PB biosensor
      was fabricated by casting the mixture of Nafion and AuNPs onto the surface of
      glassy carbon electrode to form AuNPs/Nafion film, and then, Ru(bpy)3(2+) was
      electrostatically adsorbed into the AuNPs/Nafion film; finally, the peptide
      tagged with ferrocene carboxylic acid (Fc-peptide) was self-assembled onto the
      surface of the AuNPs. When PSA was present, it specifically cleaved the Fc
      peptide, leading the quencher to leave the electrode and resulting in the
      increase of the ECL intensity obtained from the resulted electrode in 0.1 M
      phosphate buffer saline (pH 7.4) containing tri-n-propylamine. The results showed
      that the increased ECL intensity was directly linear to the logarithm of the
      concentration of PSA in the range from 5.0 * 10(-12) to 5.0 * 10(-9) g/mL. An
      extremely low detection limit of 8 * 10(-13) g/mL was achieved because of the
      signal amplification through AuNPs and the ECL background suppression through Fc
      as ECL quencher. This work demonstrates that the combination of the direct
      transduction of peptide cleavage events with the highly sensitive ECL method is a
      promising strategy for the design of enzymatic cleavage-based ECL biosensors with
      high sensitivity and selectivity. 

PMID- 24437690
TI  - Enhanced cellular entry and efficacy of tat conjugates by rational design of the
      auxiliary segment.
AB  - Conjugation with a cell penetrating peptide such as Tat presents an effective
      approach to improve the intracellular accumulation of molecules with low membrane
      permeability. This strategy, however, leads to a reduced cellular entry of
      molecules that can cross cell membrane effectively. We report here that covalent
      linkage of an additional hydrophobic unit that mimics a hydrophobic domain near
      the Tat sequence can further improve the cellular uptake of the parental
      conjugate into cancer cells regardless of the membrane permeability of the
      unconjugated molecule. Both fluorescent imaging and flow cytometry measurements
      confirmed the effect of palmitoylation on the increased internalization of the
      Tat conjugates with either 5-carboxyfluorescein (5-FAM), a nonmembrane
      penetrating dye, or doxorubicin, an anticancer cancer drug that can readily
      diffuse across cell membranes. In the case of the Tat-doxorubicin conjugate,
      palmitoylation improves the conjugate's anticancer activity in both drug
      sensitive and resistant cervical cancer cell lines. We further demonstrate that
      modification of a Tat-5-FAM conjugate with a hydrophobic quencher could not only
      efficiently quench the fluorescence outside of cancer cell but also facilitate
      its entry into MCF-7 breast cancer cells. These results highlight the importance
      of rational molecular design of using peptide conjugation chemistry in cancer
      therapeutics and diagnostics. 

PMID- 24437698
TI  - High power density of one-compartment H2O2 fuel cells using pyrazine-bridged
      Fe[M(C)(CN)4] (M(C) = Pt2+ and Pd2+) complexes as the cathode.
AB  - Pyrazine-bridged Fe[M(C)(CN)4] complexes (M(C) = Pt(2+) and Pd(2+)) with 3D
      porous structures were utilized as the cathode of one-compartment H2O2 fuel
      cells, which operated in 0.3 M H2O2, using a nickel mesh as an anode. The power
      density of a H2O2 fuel cell using pyrazine-bridged Fe[Pt(CN)4] reached 4.2 mW cm(
      2), which is the highest value reported for the one-compartment H2O2 fuel cells.
      On the other hand, H2O2 fuel cells using pyrazine-bridged M(N)[Pt(CN)4] (M(N) =
      Co(2+) and Mn(2+)) as the cathodes exhibited power densities lower than 0.01 mW
      cm(-2), indicating that Fe(2+) ions are indispensable to achieve the high power
      density. 

PMID- 24437697
TI  - High incidence of secondary hypertension in patients referred for renal
      denervation--the Copenhagen experience.
AB  - Percutaneous renal denervation is a new treatment option for patients with
      resistant hypertension and little is known about the eligibility of patients
      referred. 100 consecutive patients were referred for renal denervation from March
      2011 through September 2012. Clinical data were prospectively extracted from
      letters and documents from referring clinics and from our physical examination.
      Of the 100 patients included, 68 were men and the mean age was 60 (+/- 12) years.
      Office blood pressure was 176 (+/- 28)/99 (+/- 19) mmHg and 24-h ambulatory blood
      pressure 156 (+/- 20)/88 (+/- 13) mmHg. The mean number of antihypertensive
      agents was 4.0 (+/- 1.6). Nearly four-fifths (82%) of the patients were
      categorized as having resistant hypertension based on the criteria stated by The
      American Heart Association's stated criteria. Nine patients declined interest in
      renal denervation before completing the clinical workup program. Thus, 91
      patients were screened, and of those 51 were found to be candidates for renal
      denervation. Forty patients were not candidates, of which secondary hypertension
      was the most common cause (n = 10). Only 51% of patients referred for renal
      denervation were eligible for treatment. The prevalence of secondary hypertension
      was 10% of the referred population. Secondary hypertension should therefore be
      considered in the evaluation of candidates for renal denervation.

PMID- 24437699
TI  - Insights into the transport of aqueous quaternary ammonium cations: a combined
      experimental and computational study.
AB  - This study focuses on understanding the relative effects of ammonium substituent
      groups (we primarily consider tetramethylammonium, benzyltrimethylammonium, and
      tetraethylammonium cations) and anion species (OH(-), HCO3(-), CO3(2-), Cl(-),
      and F(-)) on ion transport by combining experimental and computational
      approaches. We characterize transport experimentally using ionic conductivity and
      self-diffusion coefficients measured from NMR. These experimental results are
      interpreted using simulation methods to describe the transport of these cations
      and anions considering the effects of the counterion. It is particularly
      noteworthy that we directly probe cation and anion diffusion with pulsed gradient
      stimulated echo NMR and molecular dynamics simulations, corroborating these
      methods and providing a direct link between atomic-resolution simulations and
      macroscale experiments. By pairing diffusion measurements and simulations with
      residence times, we were able to understand the interplay between short-time and
      long-time dynamics with ionic conductivity. With experiment, we determined that
      solutions of benzyltrimethylammonium hydroxide have the highest ionic
      conductivity (0.26 S/cm at 65  degrees C), which appears to be due to differences
      for the ions in long-time diffusion and short-time water caging. We also examined
      the effect of CO2 on ionic conductivity in ammonium hydroxide solutions. CO2
      readily reacts with OH(-) to form HCO(-)3 and is found to lower the solution
      ionic conductivity by almost 50%. 

PMID- 24437700
TI  - The isotope altitude effect reflected in groundwater: a case study from Slovenia.
AB  - This paper presents the stable isotope data of oxygen (delta(18)O) and hydrogen
      (delta(2)H) in groundwater from 83 sampling locations in Slovenia and their
      interpretation. The isotopic composition of water was monitored over 3 years
      (2009-2011), and each location was sampled twice. New findings on the isotopic
      composition of sampled groundwater are presented, and the data are also compared
      to past studies regarding the isotopic composition of precipitation, surface
      water, and groundwater in Slovenia. This study comprises: (1) the general
      characteristics of the isotopic composition of oxygen and hydrogen in groundwater
      in Slovenia, (2) the spatial distribution of oxygen isotope composition
      (delta(18)O) and d-excess in groundwater, (3) the groundwater isotope altitude
      effect, (4) the correlation between groundwater d-excess and the recharge area
      altitude of the sampling location, (5) the relation between hydrogen and oxygen
      isotopes in groundwater in comparison to the global precipitation isotope data,
      (6) the groundwater isotope effect of distance from the sea, and (7) the
      estimated relation between the mean temperature of recharge area and delta(18)O
      in groundwater. 

PMID- 24437701
TI  - Ruthenium-catalyzed hydroarylation of anilides with alkynes: an efficient route
      to ortho-alkenylated anilines.
AB  - Acetanilides reacted with symmetrical as well as unsymmetrical alkynes in the
      presence of [{RuCl2(p-cymene)}2], pivalic acid, and AgSbF6 in iso-PrOH providing
      ortho-alkenylated acetanilides in a highly regio- and stereoselective manner.
      Later, ortho-alkenylated acetanilides were converted into ortho-alkenylated
      anilines in the presence of HCl. 

PMID- 24437705
TI  - Diversity of Campylobacter in retail meat and liver of lambs and goat kids.
AB  - The presence, genetic diversity, and antimicrobial susceptibility profile of
      Campylobacter spp. in retail lamb and goat kid carcasses were assessed. A total
      of 200 samples consisting of 100 meat and 100 liver surface swabs were collected
      from 47 lamb and 53 goat kid carcasses at 23 retail markets in Northern Greece,
      and 125 Campylobacter isolates were recovered from 32 meat surfaces (32%) and 44
      liver surfaces (44%). Multiplex polymerase chain reaction and restriction
      fragment length polymorphism analysis specified Campylobacter coli as the most
      frequently detected species (59.2%) followed by C. jejuni (40.8%). Pulsed-field
      gel electrophoresis (PFGE) was applied in order to typify a subset of randomly
      selected isolates (n=80). SmaI-PFGE successfully clustered the 80 isolates in 38
      SmaI-PFGE types, indicating high heterogeneity among the analyzed Campylobacter
      isolates, and provided data regarding the dissemination of Camplobacter among
      carcasses stored in the same retail market. Antimicrobial susceptibility profiles
      of Campylobacter isolates, assessed by the disk-diffusion method, indicated that
      31 isolates (24.8%) were multidrug resistant, and the most common profile was the
      concurrent resistance to tetracycline and streptomycin. Overall, 56.8% of
      isolates (n=71, multidrug-resistant isolates included) exhibited resistance to at
      least one antimicrobial (tetracycline 34.4%, quinolones 27.2%, and streptomycin
      20.8%). However, all isolates were susceptible to erythromycin and gentamicin.
      The findings of this study verify the contamination of retail lamb and goat kid
      carcasses with a heterogeneous population of thermotolerant campylobacters. These
      data underscore the fact that retail meat and liver of small ruminants could
      serve as vehicles for consumer contamination with Campylobacter and that further
      investigation is necessary in order to evaluate the risk imposed by such products
      within the epidemiology of human campylobacteriosis cases.

PMID- 24437706
TI  - Occurrence and characterization of Cronobacter spp. in powdered formula from
      Chinese retail markets.
AB  - Cronobacter spp. (formerly known as Enterobacter sakazakii) are foodborne
      pathogens that cause rare but life-threatening diseases in neonates and infants
      through consumption of contaminated powdered infant formula. This study was
      conducted to investigate the occurrence of Cronobacter spp. in powdered formula
      in China and to further characterize Cronobacter isolates. Isolates were
      identified to the species level based on the fusA gene sequence, and strains of
      C. sakazakii were further subtyped by applying the polymerase chain reaction
      (PCR)-based serotyping method. A total of 23 strains of Cronobacter spp. isolated
      from 530 powdered formula samples were identified using conventional biochemical
      methods and duplex PCR. Cronobacter spp. were detected in 6.25%, 1.82%, 3.64%,
      5.45%, and 2.50% of the general formula, infant formula (age <6 months), follow
      up formula (6-12 months of age), growing-up formula (1-3 years of age), and
      children's formula (3-6 years of age), respectively. The individual species were
      identified as C. sakazakii (22 isolates) and C. malonaticus (1 isolate). Among 22
      C. sakazakii isolates, representatives of all but two O-antigen serotypes
      (serotypes O5 and O6) were recognized.

PMID- 24437708
TI  - Ultrasound effects on the degradation kinetics, structure, and antioxidant
      activity of sea cucumber fucoidan.
AB  - The effects of ultrasound on the molecular weight, structure, and antioxidant
      potential of a fucoidan found in Isostichopus badionotus were investigated. The
      results showed the molecular weight (Mw) of fucoidan decreased obviously after
      ultrasound treatment. Higher ultrasonic intensity, lower temperature, and lower
      fucoidan concentrations led to a more effective sonochemical effect. The kinetic
      model for fucoidan degradation fitted to 1/M(wt)-1/M(w0) = kt at the tested
      temperature. The optimized degradation conditions by response surface methodology
      (RSM) were temperature, 12  degrees C, and intensity, 508 W/cm2. Structural
      analysis by FTIR and NMR indicated the fucoidan kept the linear tetrasaccharide
      repeating units as the original polysaccharides after the ultrasound treatment,
      with only slight destruction of the middle nonsulfated fucose units. Antioxidant
      activity assay showed the antioxidant activity was slightly improved by the
      ultrasound treatment. The results suggested that ultrasound treatment is an
      effective approach to decrease the M(w) of fucoidan with only minor structural
      destruction.

PMID- 24437710
TI  - On the observation of intervalence charge transfer bands in hydrogen-bonded mixed
      valence complexes.
AB  - Ruthenium clusters of the type [Ru3(MU3-O)(OAc)6(CO)(L)(nic)], where L = 4
      dimethylaminopyridine (dmap) and nic = isonicotinic acid, form hydrogen-bonded
      mixed-valence dimers upon a single electron reduction. Electrochemical responses
      show two overlapping reduction waves, indicating the presence of a
      thermodynamically stable mixed-valence dimer with considerable electronic
      coupling across the hydrogen bond. Electronic spectra of the singly reduced
      hydrogen-bonded mixed-valence dimer reveal two intervalence charge transfer bands
      in the near-infrared region consistent with a Robin-Day class II system. These
      bands are assigned as metal-to-metal and metal-to-bridge charge transfer, and
      their behavior is best described by a semiclassical three state model. Infrared
      spectroscopy suggests localized behavior indicating electron transfer between the
      two clusters is slower than 10(10) s(-1). 

PMID- 24437714
TI  - Inductively coupled plasma mass spectrometry-based method for the specific
      quantification of sulfenic acid in peptides and proteins.
AB  - A robust ICPMS-based method is introduced to obtain relative and absolute
      quantification of sulfenic acid (SA) in peptides and proteins. A new metal
      containing reagent (Ln-DOTA-Dimedone) devised to react specifically with SA has
      been developed. The lanthanide-containing metal-coded affinity tag (Ln-MeCAT) was
      used to quantify thiol residues. We presented two approaches which allow the
      parallel and consecutive determination of SA and thiols in peptide and protein
      samples. The high sensitivity, structure-independent signal, and multiplexing
      capabilities of ICPMS together with the specificity of Ln-DOTA-Dimedone and Ln
      MeCAT toward sulfenic acid and thiol residues, respectively, allow the
      characterization of various biological states and offer closer insight onto thiol
      sulphenic acid equilibria which are involved in intracellular redox-mediated
      events altering structure and function of proteins in important diseases. 

PMID- 24437717
TI  - Relations between the geometry of cortical gyrification and white-matter network
      architecture.
AB  - A geometrically based network model of cortico-cortical white-matter connectivity
      is used in combination with diffusion spectrum MRI (DSI) data to show that white
      matter cortical network architecture is founded on a homogeneous, isotropic
      geometric connection principle. No other special information about single
      connections or groups of connections is required to generate networks very
      similar to experimental ones. This model provides excellent agreement with
      experimental DSI frequency distributions of network measures-degree, clustering
      coefficient, path length, and betweenness centrality. In the model, these
      distributions are a result of geometrically induced spatial variations in the
      values of these measures with deep nodes having more hublike properties than
      superficial nodes. This leads to experimentally testable predictions of
      corresponding variations in real cortexes. The convoluted geometry of the cortex
      is also found to introduce weak modularity, similar to the lobe structure of the
      cortex, with the boundaries between modules having hublike properties. These
      findings mean that some putative discoveries regarding the structure of white
      matter cortical networks are simply artifacts and/or consequences of geometry.
      This model may help provide insight into diseases associated with differences in
      gyrification as well as evolutionary development of the cortex.

PMID- 24437709
TI  - DNA adductomics.
AB  - Systems toxicology is a broad-based approach to describe many of the
      toxicological features that occur within a living system under stress or
      subjected to exogenous or endogenous exposures. The ultimate goal is to capture
      an overview of all exposures and the ensuing biological responses of the body.
      The term exposome has been employed to refer to the totality of all exposures,
      and systems toxicology investigates how the exposome influences health effects
      and consequences of exposures over a lifetime. The tools to advance systems
      toxicology include high-throughput transcriptomics, proteomics, metabolomics, and
      adductomics, which is still in its infancy. A well-established methodology for
      the comprehensive measurement of DNA damage resulting from every day exposures is
      not fully developed. During the past several decades, the (32)P-postlabeling
      technique has been employed to screen the damage to DNA induced by multiple
      classes of genotoxicants; however, more robust, specific, and quantitative
      methods have been sought to identify and quantify DNA adducts. Although triple
      quadrupole and ion trap mass spectrometry, particularly when using multistage
      scanning (LC-MS(n)), have shown promise in the field of DNA adductomics, it is
      anticipated that high-resolution and accurate-mass LC-MS(n) instrumentation will
      play a major role in assessing global DNA damage. Targeted adductomics should
      also benefit greatly from improved triple quadrupole technology. Once the
      analytical MS methods are fully mature, DNA adductomics along with other -omics
      tools will contribute greatly to the field of systems toxicology.

PMID- 24437718
TI  - The cytotoxicity of silver nanoparticles coated with different free fatty acids
      on the Balb/c macrophages: an in vitro study.
AB  - Nanoparticles (NPs) can adsorb different molecules, because of their high local
      charge density and specific surface area. The toxicity of NPs is changed after
      adsorption, which may be different from unbound or unbound NPs. In this study,
      unbound silver nanoparticles (Ag NPs) and Ag NPs coated with different free fatty
      acids (FFAs) including lauric acid, alpha linoleic acid, oleic acid, and palmitic
      acid were incubated with mouse macrophages for 24 hours at 37  degrees C. After
      incubation, their toxicities, reactive oxygen species (ROS) generation, and
      uptake were separately investigated. This study showed that FFA-coated Ag NPs had
      less toxicity, higher uptake, and less ROS generation than unbound Ag NPs. Based
      on the results, unbound Ag NPs aggregated in RPMI1640 medium, and their size
      distribution was near 100-1000 nm. But all FFA-coated Ag NPs had nano metric size
      (near 20--40 nm) without agglomeration.

PMID- 24437719
TI  - Finding the right (bioorthogonal) chemistry.
AB  - Bioorthogonal chemistries can be used to tag diverse classes of biomolecules in
      cells and other complex environments. With over 20 unique transformations now
      available, though, selecting an appropriate reaction for a given experiment is
      challenging. In this article, we compare and contrast the most common classes of
      bioorthogonal chemistries and provide a framework for matching the reactions with
      downstream applications. We also discuss ongoing efforts to identify novel
      biocompatible reactions and methods to control their reactivity. The continued
      expansion of the bioorthogonal toolkit will provide new insights into biomolecule
      networks and functions and thus refine our understanding of living systems. 

PMID- 24437720
TI  - Asymmetric vinylogous Mannich reaction of silyloxy furans with N-tert
      butanesulfinyl ketimines.
AB  - A highly regio- and diastereoselective TMSOTf promoted vinylogous Mannich
      reaction for the synthesis of chiral quaternary 3-aminooxindole butenolides from
      2-silyloxy furans and chiral ketimines is described. The method is found to be
      very efficient and also provides a facile access to sterically challenging 3
      aminooxindole butenolides bearing two quaternary centers in continuation.
      Further, the versatility of the method is demonstrated by the 1,4-addition of
      nucleophiles on the sterically congested butenolide substructure. 

PMID- 24437721
TI  - Influence of casein-phospholipid combinations as emulsifier on the physical and
      oxidative stability of fish oil-in-water emulsions.
AB  - The objective of this study was to investigate the influence of casein (0.3% w/w)
      and phospholipid (0.5% w/w) emulsifier combinations on the physical and oxidative
      stability of 10% fish oil-in-water emulsions at pH 7. For that purpose, three
      phospholipids were evaluated, namely, lecithin (LC), phosphatidylcholine (PC),
      and phosphatidylethanolamine (PE). The emulsion stabilized with LC showed the
      best physical stability having the most negative zeta potential and the lowest
      mean droplet size. In addition, this emulsion was also the least oxidized in
      terms of peroxide value and concentration of the volatile oxidation product 1
      penten-3-ol. This finding is not explained by the antioxidant activity of LC
      because it showed similar DPPH scavenging activity and lower metal chelating
      activity than the other phospholipids. Therefore, these results suggested that
      other factors such as the combination of casein and lecithin, which could result
      in a favorable structure and thickness of the interfacial layer, prevented lipid
      oxidation in this emulsion. 

PMID- 24437729
TI  - Inhibitory effect of selenoprotein P on Cu(+)/Cu(2+)-induced Abeta42 aggregation
      and toxicity.
AB  - It has been suggested that the aggregation and cytotoxicity of amyloid-beta
      (Abeta) peptide with transition-metal ions in neuronal cells is involved in the
      progression of Alzheimer's disease (AD). Selenoproteins are a group of special
      proteins that contain the 21st amino acid selenocysteine in their sequence, and
      they are found to be involved in the onset and progression of AD. Here, we report
      that the histidine-rich domain of selenoprotein P (SelP-H) is capable of binding
      Cu ions in both oxidation states of Cu(+) and Cu(2+) with high affinity and of
      modulating Cu(+) and Cu(2+)-mediated Abeta aggregation, reactive oxygen species
      (ROS) production, and neurotoxicity. SelP-H was found to coordinate 1 and 2 mol
      equiv of Cu(+) and Cu(2+) with sub-picomolar and nanomolar affinities,
      respectively. Cu(+)/Cu(2+) binding to Abeta42 inhibited the fibrillization of
      Abeta42 but induced it to form amorphous aggregates, which could be significantly
      restored by SelP-H, as observed by thioflavin T fluorescence and transmission
      electron microscopy. Interestingly, SelP-H inhibited Cu(+)/Cu(2+)-Abeta42-induced
      neurotoxicity and the intracellular ROS production in living cells. These studies
      suggest that SelP may play certain roles in regulating redox balance as well as
      metal homeostasis. 

PMID- 24437730
TI  - Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical
      detection for tunable, targeted, multimodal imaging in vivo.
AB  - Understanding the complex nature of diseased tissue in vivo requires development
      of more advanced nanomedicines, where synthesis of multifunctional polymers
      combines imaging multimodality with a biocompatible, tunable, and functional
      nanomaterial carrier. Here we describe the development of polymeric nanoparticles
      for multimodal imaging of disease states in vivo. The nanoparticle design
      utilizes the abundant functionality and tunable physicochemical properties of
      synthetically robust polymeric systems to facilitate targeted imaging of tumors
      in mice. For the first time, high-resolution (19)F/(1)H magnetic resonance
      imaging is combined with sensitive and versatile fluorescence imaging in a
      polymeric material for in vivo detection of tumors. We highlight how control over
      the chemistry during synthesis allows manipulation of nanoparticle size and
      function and can lead to very high targeting efficiency to B16 melanoma cells,
      both in vitro and in vivo. Importantly, the combination of imaging modalities
      within a polymeric nanoparticle provides information on the tumor mass across
      various size scales in vivo, from millimeters down to tens of micrometers. 

PMID- 24437731
TI  - Calcium-ammonium exchange experiments on clay minerals using a (45)Ca tracer
      technique in marine pore water.
AB  - Understanding cation exchange processes is important for evaluating early
      diagenetic and synsedimentary processes taking place in marine sediments. To
      quantify calcium (Ca) exchange and Ca-ammonium exchange in a seawater
      environment, we performed experiments with a radioactive (45)Ca tracer on clay
      mineral standards (Fithian illite, montmorillonite and kaolinite) and marine
      sediments from the North Atlantic Integrated Ocean Drilling Program Site U1306A
      in artificial seawater (ASW). The results show that equilibrium during the
      initial attachment of Ca as well as the exchange of Ca by [Formula: see text] is
      attained in less than 2 min. On average 8-20% of the exchangeable sites of the
      clay minerals were occupied by Ca in a seawater medium. The conditional
      selectivity coefficient, describing the [Formula: see text] exchange in ASW is
      mineral specific and it was determined to be 0.07 for montmorillonite, 0.05 for a
      natural marine sediment and 0.013 for Fithian illite. 

PMID- 24437734
TI  - Urinary metabolic fingerprint of acute intermittent porphyria analyzed by (1)H
      NMR spectroscopy.
AB  - (1)H NMR is a nonbiased technique for the quantification of small molecules that
      could result in the identification and characterization of potential biomarkers
      with prognostic value and contribute to better understand pathophysiology of
      diseases. In this study, we used (1)H NMR spectroscopy to analyze the urinary
      metabolome of patients with acute intermittent porphyria (AIP), an inherited
      metabolic disorder of heme biosynthesis in which an accumulation of the heme
      precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG) promotes sudden
      neurovisceral attacks, which can be life-threatening. Our objectives were (1) to
      demonstrate the usefulness of (1)H NMR to identify and quantify ALA and PBG in
      urines from AIP patients and (2) to identify metabolites that would predict the
      response to AIP crisis treatment and reflect differential metabolic
      reprogramming. Our results indicate that (1)H NMR can help to diagnose AIP
      attacks based on the identification of ALA and PBG. We also show that glycin
      concentration increases in urines from patients with frequent recurrences at the
      end of the treatment, after an initial decrease, whereas PBG concentration
      remains low. Although the reasons for this altered are elusive, these findings
      indicate that a glycin metabolic reprogramming occurs in AIPr patients and is
      associated with recurrence. Our results validate the proof of concept of the
      usefulness of (1)H NMR spectroscopy in clinical chemistry for the diagnosis of
      acute attack of AIP and identify urinary glycin as a potential marker of
      recurrence of AIP acute attacks. 

PMID- 24437736
TI  - Reducing loneliness amongst older people: a systematic search and narrative
      review.
AB  - OBJECTIVE: To investigate the effectiveness of recent social therapeutic
      interventions to reduce loneliness in older people. METHOD: To examine this
      matter, a literature review, using seven databases, was undertaken using search
      terms relating to the themes of ageing, loneliness and social support. A total of
      17 relevant studies relating to loneliness interventions were analysed. RESULTS:
      Three studies reporting on new technologies and one on a group work intervention
      identified significant reductions in loneliness. CONCLUSION: Further research
      into interventions using new technologies to reduce loneliness in older people is
      recommended.

PMID- 24437739
TI  - Differences in subjective loudness and annoyance depending on the road traffic
      noise spectrum.
AB  - There is at present no consensus about the relative importance of low frequency
      content in urban road traffic noise. The hypothesis underlying this research is
      that changes to different parts of the spectrum will have different effects
      depending on which part of the spectrum is subjectively dominant in any
      particular situation. This letter reports a simple listening experiment which
      demonstrates this effect using typical urban main road traffic noise in which the
      low frequency content is physically dominant without necessarily being
      subjectively dominant. 

PMID- 24437735
TI  - Design, synthesis, and evaluation of conformationally restricted acetanilides as
      potent and selective beta3 adrenergic receptor agonists for the treatment of
      overactive bladder.
AB  - A series of conformationally restricted acetanilides were synthesized and
      evaluated as beta3-adrenergic receptor agonists (beta3-AR) for the treatment of
      overactive bladder (OAB). Optimization studies identified a five-membered ring as
      the preferred conformational lock of the acetanilide. Further optimization of
      both the aromatic and thiazole regions led to compounds such as 19 and 29, which
      have a good balance of potency and selectivity. These compounds have
      significantly reduced intrinsic clearance compared to our initial series of
      pyridylethanolamine beta3-AR agonists and thus have improved unbound drug
      exposures. Both analogues demonstrated dose dependent beta3-AR mediated responses
      in a rat bladder hyperactivity model. 

PMID- 24437740
TI  - Scattering of ultrasonic waves by heterogeneous interfaces: formulating the
      direct scattering problem as a least-squares problem.
AB  - An analytic-numerical method to simulate the interaction of time-harmonic
      ultrasonic waves with imperfectly bonded layered structures is presented. In the
      proposed formulation, elastic layers may be either isotropic or anisotropic and
      adhesion interfaces are replaced by equivalent continuous distribution of normal
      and transversal springs. In addition, adhesion imperfections are allowed to be
      localized in space and are modeled by a corresponding local reduction in spring
      constants. The resulting direct scattering problem is formulated as a least
      squares problem and solved accordingly. The formulation was extended for three
      different cases: Scattering from imperfectly bonded half-spaces, scattering from
      imperfectly bonded layered structures and scattering from imperfectly bonded
      layered plates immersed in acoustic fluid, and numerical simulations
      corresponding to each one of these cases are presented. The simulations indicate
      that the method is capable of capturing the scattering resulting from the
      interaction of ultrasonic waves with defective bonds as well as indicate that
      ultrasound has the potential of revealing the presence of defective bonds and
      interfacial heterogeneities. 

PMID- 24437741
TI  - Finite-difference simulations of transient radiation from a finite-length pipe.
AB  - The far-field radiation originating from a finite-length pipe is well studied,
      especially for steady-state conditions. However, because all physical systems do
      not begin in steady state, these radiation characteristics are only valid after
      the transient portion of the solution has decayed. Understanding transient
      radiation characteristics may be important (particularly for systems transmitting
      very short-duration signals), as they can differ quite significantly. A numerical
      complication to this problem involves dealing with a sharp corner in the domain
      of interest. While many numerical studies have attempted to couple solutions from
      the domains inside and outside a pipe, the analysis presented in this work treats
      the computational domain as a single region by expressing the entire physical
      domain as a map from a simple rectangular domain in generalized curvilinear
      coordinates. This method will be introduced in detail and general results of
      transient radiation will be presented for an infinitely baffled, finite-length
      pipe using the finite-difference method expressed in generalized curvilinear
      coordinates. Comparison will be made to previous results [P. Stepanishen and R.
      A. Tougas, J. Acoust. Soc. Am. 93, 3074-3084 (1993)] that used a semi-analytic
      approach with certain assumptions. 

PMID- 24437742
TI  - Experimental investigation of acoustic streaming in a cylindrical wave guide up
      to high streaming Reynolds numbers.
AB  - Measurements of streaming velocity are performed by means of Laser Doppler
      Velocimetry and Particle Image Velociimetry in an experimental apparatus
      consisting of a cylindrical waveguide having one loudspeaker at each end for high
      intensity sound levels. The case of high nonlinear Reynolds number ReNL is
      particularly investigated. The variation of axial streaming velocity with respect
      to the axial and to the transverse coordinates are compared to available Rayleigh
      streaming theory. As expected, the measured streaming velocity agrees well with
      the Rayleigh streaming theory for small ReNL but deviates significantly from such
      predictions for high ReNL. When the nonlinear Reynolds number is increased, the
      outer centerline axial streaming velocity gets distorted towards the acoustic
      velocity nodes until counter-rotating additional vortices are generated near the
      acoustic velocity antinodes. This kind of behavior is followed by outer streaming
      cells only and measurements in the near wall region show that inner streaming
      vortices are less affected by this substantial evolution of fast streaming
      pattern. Measurements of the transient evolution of streaming velocity provide an
      additional insight into the evolution of fast streaming. 

PMID- 24437743
TI  - Modeling propagation of infrasound signals observed by a dense seismic network.
AB  - The long-range propagation of infrasound from a surface explosion with an
      explosive yield of about 17.6 t TNT that occurred on June 16, 2008 at the Utah
      Test and Training Range (UTTR) in the western United States is simulated using an
      atmospheric model that includes fine-scale layered structure of the wind velocity
      and temperature fields. Synthetic signal parameters (waveforms, amplitudes, and
      travel times) are calculated using parabolic equation and ray-tracing methods for
      a number of ranges between 100 and 800 km from the source. The simulation shows
      the evolution of several branches of stratospheric and thermospheric signals with
      increasing range from the source. Infrasound signals calculated using a G2S
      (ground-to-space) atmospheric model perturbed by small-scale layered wind
      velocity and temperature fluctuations are shown to agree well with recordings
      made by the dense High Lava Plains seismic network located at an azimuth of 300
      degrees  from UTTR. The waveforms of calculated infrasound arrivals are compared
      with those of seismic recordings. This study illustrates the utility of dense
      seismic networks for mapping an infrasound field with high spatial resolution.
      The parabolic equation calculations capture both the effect of scattering of
      infrasound into geometric acoustic shadow zones and significant temporal
      broadening of the arrivals. 

PMID- 24437744
TI  - Comparison of acoustic and seismic excitation, propagation, and scattering at an
      air-ground interface containing a mine-like inclusion.
AB  - Finite element methods are utilized to model and compare the use of both a remote
      loudspeaker and a vertical shaker in the generation of sound and shear and
      interface waves in an elastic solid containing an imbedded elastic scatterer,
      which is resonant. Results for steady state and transient insonification are
      presented to illustrate excitation, propagation, and scattering mechanisms and
      effects. Comparisons of acoustic and vibratory excitation of the solid interface
      are made, with a view towards remote sensing of induced vibratory motion through
      optical measurement of the ground interface motion above the imbedded inclusion.
      Some advantages of the acoustic excitation method for exciting plate mode
      resonances in the target are observed. 

PMID- 24437745
TI  - Heuristic approximations for sound fields produced by spherical waves incident on
      locally and non-locally reacting planar surfaces.
AB  - The classic Weyl-van der Pol (WVDP) formula is a well-known asymptotic solution
      for accurately predicting sound fields above a locally reacting ground surface.
      However, the form of the WVDP formula is inadequate for predicting sound fields
      in the vicinity of non-locally reacting surfaces; a correction term is often
      required in the formula to provide accurate numerical solutions. Even with this
      correction, there is a singularity in the diffraction wave term when the source
      is located directly above or below the receiver. This paper explores a heuristic
      method to remove this singularity and suggests an analytical form comparable to
      the WVDP formula. This improved formula offers a physically interpretable
      solution and allows for accurate predictions of the total sound field above
      locally and non-locally reacting surfaces for all geometrical configurations. 

PMID- 24437746
TI  - Amplitude modulation of sound from wind turbines under various meteorological
      conditions.
AB  - Wind turbine (WT) sound annoys some people even though the sound levels are
      relatively low. This could be because of the amplitude modulated "swishing"
      characteristic of the turbine sound, which is not taken into account by standard
      procedures for measuring average sound levels. Studies of sound immission from
      WTs were conducted continually between 19 August 2011 and 19 August 2012 at two
      sites in Sweden. A method for quantifying the degree and strength of amplitude
      modulation (AM) is introduced here. The method reveals that AM at the immission
      points occur under specific meteorological conditions. For WT sound immission,
      the wind direction and sound speed gradient are crucial for the occurrence of AM.
      Interference between two or more WTs could probably enhance AM. The mechanisms by
      which WT sound is amplitude modulated are not fully understood. 

PMID- 24437747
TI  - Low frequency acoustic resonances in urban courtyards.
AB  - Urban courtyards can be regarded as open cavities in the urban area, in which
      resonances can be excited by waves generated in the neighboring streets. The aim
      of the present work is to experimentally and numerically investigate low
      frequency resonance phenomena in these configurations. Experiments are carried
      out in a scale model and a numerical study is performed with a coupled modal
      finite elements method. The method enables the three-dimensional modeling of the
      acoustic field and thus to take into account the interactions between the
      courtyard and the street canyon that occur above the roof level, a particular
      characteristic of wave propagation in urban areas. The attention is focused on
      two aspects, the amplification of the sound level inside the courtyard and the
      acoustic attenuation in the street due to resonances. Experimental and numerical
      results are in good agreement and show a strong resonant behavior of these
      configurations. 

PMID- 24437748
TI  - Simulating acoustic scattering from atmospheric temperature fluctuations using a
      k-space method.
AB  - This paper describes a numerical method for simulating far-field scattering from
      small regions of inhomogeneous temperature fluctuations. Such scattering is of
      interest since it is the mechanism by which acoustic wind velocity profiling
      devices (Doppler SODAR) receive backscatter. The method may therefore be used to
      better understand the scattering mechanisms in operation and may eventually
      provide a numerical test-bed for developing improved SODAR signals and post
      processing algorithms. The method combines an analytical incident sound model
      with a k-space model of the scattered sound close to the inhomogeneous region and
      a near-to-far-field transform to obtain far-field scattering patterns. Results
      from two test case atmospheres are presented: one with periodic temperature
      fluctuations with height and one with stochastic temperature fluctuations given
      by the Kolmogorov spectrum. Good agreement is seen with theoretically predicted
      far-field scattering and the implications for multi-frequency SODAR design are
      discussed. 

PMID- 24437749
TI  - Frequency-domain model of tonal blade thickness and loading noise.
AB  - A tonal thickness noise and loading noise model of rotating blades has been
      developed as an extension of the exact frequency-domain solutions for rotating
      monopole and dipole point sources. The present model has two advantages over the
      previous methods and models for noise prediction. The first is the unified
      expression for sources in subsonic and supersonic rotation even at rest. The
      second is that the present model has no limit on the location of the observer and
      no interpolation error. Two test cases are carried out to validate the present
      model and emphasize its advantage at the noise prediction for sources in
      supersonic rotation. Moreover, as a specified application of the present model
      for the rotating blades whose tip radius is acoustically compact, acoustic energy
      distribution at different frequencies and in different directions is analyzed.
      Result shows that the acoustic energy of acoustically compact rotating blades is
      mainly concentrated at the source frequency while propagating along the axial
      direction, leaving the rest propagating along the radial direction at the other
      frequencies. 

PMID- 24437750
TI  - A statistical-based approach for acoustic tomography of the atmosphere.
AB  - Acoustic travel-time tomography of the atmosphere is a nonlinear inverse problem
      which attempts to reconstruct temperature and wind velocity fields in the
      atmospheric surface layer using the dependence of sound speed on temperature and
      wind velocity fields along the propagation path. This paper presents a
      statistical-based acoustic travel-time tomography algorithm based on dual state
      parameter unscented Kalman filter (UKF) which is capable of reconstructing and
      tracking, in time, temperature, and wind velocity fields (state variables) as
      well as the dynamic model parameters within a specified investigation area. An
      adaptive 3-D spatial-temporal autoregressive model is used to capture the state
      evolution in the UKF. The observations used in the dual state-parameter UKF
      process consist of the acoustic time of arrivals measured for every pair of
      transmitter/receiver nodes deployed in the investigation area. The proposed
      method is then applied to the data set collected at the Meteorological
      Observatory Lindenberg, Germany, as part of the STINHO experiment, and the
      reconstruction results are presented. 

PMID- 24437751
TI  - Seismo-acoustic propagation near thin and low-shear speed ocean bottom sediments
      using a massive elastic interface.
AB  - The seafloor is considered to be a thin surface layer overlying an elastic half
      space. In addition to layers of this type being thin, they may also have shear
      wave speeds that can be small (order 100 m/s). Both the thin and low-shear
      properties, viewed as small parameters, can cause mathematical and numerical
      singularities to arise. Following the derivation presented by Gilbert [Geophys.
      J. Int. 133, 230-232 (1998)], the surface layer is approximated as a thick,
      finite-thickness interface, and modified ocean bottom fluid-solid interface
      conditions are derived as jump conditions across the interface. The resultant
      interface conditions are incorporated into a seismo-acoustic parabolic equation
      solution, and this interface-based solution is benchmarked against existing
      solutions and previously derived modified fluid-solid interface jump conditions.
      Accuracy quantification is given via dimensionless interface thickness
      parameters. 

PMID- 24437752
TI  - Three-dimensional localization of transient acoustic sources using an ice-mounted
      geophone.
AB  - This paper presents an approach to three-dimensional (3D) localization of ocean
      acoustic sources using a single three-component geophone on Arctic sea ice.
      Source bearing is estimated by maximizing the radial signal power as a function
      of horizontal look angle, applying seismic polarization filters to suppress shear
      waves with transverse particle motion. The inherent 180 degrees  ambiguity is
      resolved by requiring outgoing (prograde) particle motion in the radial-vertical
      plane. Source range and depth estimates and uncertainties are computed by
      Bayesian inversion of arrival-time differences of the water-borne acoustic wave
      and ice seismic waves, including the horizontally-polarized shear wave and
      longitudinal plate wave. The 3D localization is applied to geophone recordings of
      impulsive sources deployed in the water column at a series of ranges (200 to 1000
      m) and bearings (0 degrees  to 90 degrees ) for three sites in the Lincoln Sea
      characterized by smooth annual ice, rough/ridged annual ice, and thick multi-year
      ice. Good bearing estimates are obtained in all cases. Range-depth localization
      is successful for ranges over which ice seismic arrivals could be reliably
      detected, approximately 200 m on rough ice, 500 m on smooth ice, and 800 m on
      multi-year ice. Effects of environmental uncertainty on localization are
      quantified by marginalizing over unknown environmental parameters. 

PMID- 24437753
TI  - Round-robin multiple-source localization.
AB  - This paper introduces a round-robin approach for multi-source localization based
      on matched-field processing. Each new source location is estimated from the
      ambiguity function after nulling from the data vector the current source location
      estimates using a robust projection matrix. This projection matrix effectively
      minimizes mean-square energy near current source location estimates subject to a
      rank constraint that prevents excessive interference with sources outside of
      these neighborhoods. Numerical simulations are presented for multiple sources
      transmitting through a fixed (and presumed known) generic Pekeris ocean waveguide
      in the single-frequency and broadband-coherent cases that illustrate the
      performance of the proposed approach which compares favorably against other
      previously published approaches. Furthermore, the efficacy with which randomized
      back-propagations may also be incorporated for computational advantage is also
      presented. 

PMID- 24437754
TI  - Group velocity of cylindrical guided waves in anisotropic laminate composites.
AB  - An explicit expression for the group velocity of wave packets, propagating in a
      laminate anisotropic composite plate in prescribed directions, is proposed. It is
      based on the cylindrical guided wave asymptotics derived from the path integral
      representation for wave fields generated in the composites by given localized
      sources. The expression derived is theoretically confirmed by the comparison with
      a known representation for the group velocity vector of a plane guided wave. Then
      it is experimentally validated against laser vibrometer measurements of guided
      wave packets generated by a piezoelectric wafer active sensor in a composite
      plate. 

PMID- 24437755
TI  - Performance of tonpilz transducers with segmented piezoelectric stacks using
      materials with high electromechanical coupling coefficient.
AB  - Tonpilz acoustic transducers for use underwater often include a stack of
      piezoelectric material pieces polarized along the length of the stack and having
      alternating polarity. The pieces are interspersed with electrodes, bonded
      together, and electrically connected in parallel. The stack is normally much
      shorter than a quarter wavelength at the fundamental resonance frequency so that
      the mechanical behavior of the transducer is not affected by the segmentation.
      When the transducer bandwidth is less than a half octave, as has conventionally
      been the case, for example, with lead zirconate titanate (PZT) material, stack
      segmentation has no significant effect on the mechanical behavior of the device
      in its normal operating band near the fundamental resonance. However, when a high
      coupling coefficient material such as lead magnesium niobate-lead titanate (PMN
      PT) is used to achieve a wider bandwidth with the tonpilz, the performance
      difference between a segmented stack and a similar piezoelectric section with
      electrodes only at the two ends can be significant. This paper investigates the
      effects of stack segmentation on the performance of wideband underwater tonpilz
      acoustic transducers. Included is a discussion of a particular tonpilz transducer
      design using single crystal piezoelectric material with high coupling coefficient
      compared with a similar design using more traditional PZT ceramics. 

PMID- 24437756
TI  - Wave propagation through penetrable scatterers in a waveguide and through a
      penetrable grating.
AB  - A multimodal method based on the admittance matrix is used to analyze wave
      propagation through scatterers of arbitrary shape. Two cases are considered: a
      waveguide containing scatterers, and the scattering of a plane wave at oblique
      incidence to an infinite periodic row of scatterers. In both cases, the problem
      reduces to a system of two sets of first-order differential equations for the
      modal components of the wavefield, similar to the system obtained in the rigorous
      coupled wave analysis. The system can be solved numerically using the admittance
      matrix, which leads to a stable numerical method, the basic properties of which
      are discussed (convergence, reciprocity, energy conservation). Alternatively, the
      admittance matrix can be used to get analytical results in the weak scattering
      approximation. This is done using the plane wave approximation, leading to a
      generalized version of the Webster equation and using a perturbative method to
      analyze the Wood anomalies and Fano resonances. 

PMID- 24437757
TI  - Variational formulation of the Stevens-Tiersten equation and application in the
      analysis of rectangular trapped-energy quartz resonators.
AB  - The two-dimensional scalar differential equation for transversely varying
      thickness modes in quartz crystal resonators operating with thickness-shear modes
      is formulated into variational form for trapped-energy resonators with both
      electroded and unelectroded regions. A theoretical analysis of rectangular
      trapped-energy resonators of singly rotated quartz is performed using the Ritz
      method based on the variational formulation. Free vibration resonant frequencies
      and modes are obtained. The results show the existence of trapped modes under the
      electrodes. The effects of various geometric and physical parameters on the
      trapped modes are examined. It is also found that the classical frequency
      prediction given by Tiersten and Smythe from an approximate analysis using the
      scalar differential equation has an inaccuracy on the order of 100 ppm for the
      fundamental mode, significant in resonator design. 

PMID- 24437758
TI  - Human response to vibration in residential environments.
AB  - This paper presents the main findings of a field survey conducted in the United
      Kingdom into the human response to vibration in residential environments. The
      main aim of this study was to derive exposure-response relationships for
      annoyance due to vibration from environmental sources. The sources of vibration
      considered in this paper are railway and construction activity. Annoyance data
      were collected using questionnaires conducted face-to-face with residents in
      their own homes. Questionnaires were completed with residents exposed to railway
      induced vibration (N = 931) and vibration from the construction of a light rail
      system (N = 350). Measurements of vibration were conducted at internal and
      external positions from which estimates of 24-h vibration exposure were derived
      for 1073 of the case studies. Sixty different vibration exposure descriptors
      along with 6 different frequency weightings were assessed as potential predictors
      of annoyance. Of the exposure descriptors considered, none were found to be a
      better predictor of annoyance than any other. However, use of relevant frequency
      weightings was found to improve correlation between vibration exposure and
      annoyance. A unified exposure-response relationship could not be derived due to
      differences in response to the two sources so separate relationships are
      presented for each source. 

PMID- 24437759
TI  - Effect of situational, attitudinal and demographic factors on railway vibration
      annoyance in residential areas.
AB  - Railway induced vibration is an important source of annoyance among residents
      living in the vicinity of railways. Annoyance increases with vibration magnitude.
      However, these correlations between the degree of annoyance and vibration
      exposure are weak. This suggests that railway vibration induced annoyance is
      governed by more than just vibration level and therefore other factors may
      provide information to understand the wide variation in annoyance reactions.
      Factors coming into play when considering an exposure-response relationship
      between level of railway vibration and annoyance are presented. The factors
      investigated were: attitudinal, situational and demographic factors. This was
      achieved using data from field studies comprised of face-to-face interviews and
      internal vibration measurements (N = 755). It was found that annoyance scores
      were strongly influenced by two attitudinal factors: Concern of property damage
      and expectations about future levels of vibration. Type of residential area and
      age of the respondent were found to have an important effect on annoyance whereas
      visibility of the railway and time spent at home showed a significant but small
      influence. These results indicate that future railway vibration policies and
      regulations focusing on community impact need to consider additional factors for
      an optimal assessment of railway effects on residential environments. 

PMID- 24437760
TI  - Exposure-response relationships for annoyance due to freight and passenger
      railway vibration exposure in residential environments.
AB  - In this work, exposure-response relationships for annoyance due to freight and
      passenger railway vibration exposure in residential environments are developed,
      so as to better understand the differences in human response to these two sources
      of environmental vibration. Data for this research come from a field study
      comprising interviews with respondents and measurements of their vibration
      exposure (N = 752). A logistic regression model is able to accurately classify
      96% of these measured railway vibration signals as freight or passenger based on
      two signal properties that quantify the duration and low frequency content of
      each signal. Exposure-response relationships are then determined using ordinal
      probit modeling with fixed thresholds. The results indicate that people are able
      to distinguish between freight and passenger railway vibration, and that the
      annoyance response due to freight railway vibration is significantly higher than
      that due to passenger railway vibration, even for equal levels of exposure. In
      terms of a community tolerance level, the population studied is 15 dB (re 10(-6)
      m s(-2)) more tolerant to passenger railway vibration than freight railway
      vibration. These results have implications for the expansion of freight traffic
      on rail, or for policies to promote passenger railway. 

PMID- 24437761
TI  - Nocturnal air, road, and rail traffic noise and daytime cognitive performance and
      annoyance.
AB  - Various studies indicate that at the same noise level and during the daytime,
      annoyance increases in the order of rail, road, and aircraft noise. The present
      study investigates if the same ranking can be found for annoyance to nocturnal
      exposure and next day cognitive performance. Annoyance ratings and performance
      change during combined noise exposure were also tested. In the laboratory 72
      participants were exposed to air, road, or rail traffic noise and all
      combinations. The number of noise events and LAS,eq were kept constant. Each
      morning noise annoyance questionnaires and performance tasks were administered.
      Aircraft noise annoyance ranked first followed by railway and road noise. A
      possible explanation is the longer duration of aircraft noise events used in this
      study compared to road and railway noise events. In contrast to road and rail
      traffic, aircraft noise annoyance was higher after nights with combined exposure.
      Pooled noise exposure data showed small but significant impairments in reaction
      times (6 ms) compared to nights without noise. The noise sources did not have a
      differential impact on performance. Combined exposure to multiple traffic noise
      sources did not induce stronger impairments than a single noise source. This was
      reflected also in low workload ratings. 

PMID- 24437762
TI  - Mean-free-paths in concert and chamber music halls and the correct method for
      calibrating dodecahedral sound sources.
AB  - The Eyring/Sabine equations assume that in a large irregular room a sound wave
      travels in straight lines from one surface to another, that the surfaces have an
      average sound absorption coefficient alphaav, and that the mean-free-path between
      reflections is 4 V/Stot where V is the volume of the room and Stot is the total
      area of all of its surfaces. No account is taken of diffusivity of the surfaces.
      The 4 V/Stot relation was originally based on experimental determinations made by
      Knudsen (Architectural Acoustics, 1932, pp. 132-141). This paper sets out to test
      the 4 V/Stot relation experimentally for a wide variety of unoccupied concert and
      chamber music halls with seating capacities from 200 to 5000, using the measured
      sound strengths Gmid and reverberation times RT60,mid. Computer simulations of
      the sound fields for nine of these rooms (of varying shapes) were also made to
      determine the mean-free-paths by that method. The study shows that 4 V/Stot is an
      acceptable relation for mean-free-paths in the Sabine/Eyring equations except for
      halls of unusual shape. Also demonstrated is the proper method for calibrating
      the dodecahedral sound source used for measuring the sound strength G, i.e., the
      reverberation chamber method. 

PMID- 24437764
TI  - Relationships between preference ratings, sensory profiles, and acoustical
      measurements in concert halls.
AB  - Preferences of concert hall acoustics are explored with preference mapping. The
      investigation is performed on previously gathered data from individual vocabulary
      profiling of nine concert halls and three pieces of symphonic music, namely,
      excerpts of compositions by Beethoven, Bruckner, and Mozart. Individual
      preferences are regressed onto a latent three-dimensional sensory space obtained
      by multiple factor analysis of descriptive sensory data. Overlaying individually
      estimated preference surfaces onto one another produces preference maps which
      illustrates both the overall preference of the stimuli as well as differences
      between individual listeners. A comparison of the maps between music motifs
      illustrates how each music signal affects the weighting of different acoustical
      qualities in preference judgments. Differences in preferences between individuals
      are pronounced in the excerpts of Beethoven and Bruckner, while the responses are
      more homogeneous for Mozart music motif. Overall, proximity is identified as the
      main aspect associated with preference, but also loudness, envelopment, and bass
      are important. A correlation analysis of objective parameters and subjective
      perceptions substantiates the importance of lateral sound energy for good concert
      hall acoustics. Particularly, the lateral early energy fraction at high
      frequencies is found to be associated with the perception of proximity, and
      hence, also with preference. 

PMID- 24437763
TI  - Sound absorption of a finite micro-perforated panel backed by a shunted
      loudspeaker.
AB  - Deep back cavities are usually required for micro-perforated panel (MPP)
      constructions to achieve good low frequency absorption. To overcome the problem,
      a close-box loudspeaker with a shunted circuit is proposed to substitute the back
      wall of the cavity of the MPP constructions to constitute a composite absorber.
      Based on the equivalent circuit model, the acoustic impedance of the shunted
      loudspeaker is formulated first, then a prediction model of the sound absorption
      of the MPP backed by shunted loudspeaker is developed by employing the mode
      solution of a finite size MPP coupled by an air cavity with an impendence back
      wall. The MPP absorbs mid to high frequency sound, and with properly adjusted
      electrical parameters of its shunted circuit, the shunted loudspeaker absorbs low
      frequency sound, so the composite absorber provides a compact solution to
      broadband sound control. Numerical simulations and experiments are carried out to
      validate the model. 

PMID- 24437765
TI  - Physical and numerical constraints in source modeling for finite difference
      simulation of room acoustics.
AB  - In finite difference time domain simulation of room acoustics, source functions
      are subject to various constraints. These depend on the way sources are injected
      into the grid and on the chosen parameters of the numerical scheme being used.
      This paper addresses the issue of selecting and designing sources for finite
      difference simulation, by first reviewing associated aims and constraints, and
      evaluating existing source models against these criteria. The process of exciting
      a model is generalized by introducing a system of three cascaded filters,
      respectively, characterizing the driving pulse, the source mechanics, and the
      injection of the resulting source function into the grid. It is shown that hard,
      soft, and transparent sources can be seen as special cases within this unified
      approach. Starting from the mechanics of a small pulsating sphere, a parametric
      source model is formulated by specifying suitable filters. This physically
      constrained source model is numerically consistent, does not scatter incoming
      waves, and is free from zero- and low-frequency artifacts. Simulation results are
      employed for comparison with existing source formulations in terms of meeting the
      spectral and temporal requirements on the outward propagating wave. 

PMID- 24437766
TI  - Sonar target enhancement by shrinkage of incoherent wavelet coefficients.
AB  - Background reverberation can obscure useful features of the target echo response
      in broadband low-frequency sonar images, adversely affecting detection and
      classification performance. This paper describes a resolution and phase
      preserving means of separating the target response from the background
      reverberation noise using a coherence-based wavelet shrinkage method proposed
      recently for de-noising magnetic resonance images. The algorithm weights the
      image wavelet coefficients in proportion to their coherence between different
      looks under the assumption that the target response is more coherent than the
      background. The algorithm is demonstrated successfully on experimental synthetic
      aperture sonar data from a broadband low-frequency sonar developed for buried
      object detection. 

PMID- 24437767
TI  - Spatial sound field synthesis and upmixing based on the equivalent source method.
AB  - Given scarce number of recorded signals, spatial sound field synthesis with an
      extended sweet spot is a challenging problem in acoustic array signal processing.
      To address the problem, a synthesis and upmixing approach inspired by the
      equivalent source method (ESM) is proposed. The synthesis procedure is based on
      the pressure signals recorded by a microphone array and requires no source model.
      The array geometry can also be arbitrary. Four upmixing strategies are adopted to
      enhance the resolution of the reproduced sound field when there are more channels
      of loudspeakers than the microphones. Multi-channel inverse filtering with
      regularization is exploited to deal with the ill-posedness in the reconstruction
      process. The distance between the microphone and loudspeaker arrays is optimized
      to achieve the best synthesis quality. To validate the proposed system, numerical
      simulations and subjective listening experiments are performed. The results
      demonstrated that all upmixing methods improved the quality of reproduced target
      sound field over the original reproduction. In particular, the underdetermined
      ESM interpolation method yielded the best spatial sound field synthesis in terms
      of the reproduction error, timbral quality, and spatial quality. 

PMID- 24437768
TI  - Updated parameters and expanded simulation options for a model of the auditory
      periphery.
AB  - A phenomenological model of the auditory periphery in cats was previously
      developed by Zilany and colleagues [J. Acoust. Soc. Am. 126, 2390-2412 (2009)] to
      examine the detailed transformation of acoustic signals into the auditory-nerve
      representation. In this paper, a few issues arising from the responses of the
      previous version have been addressed. The parameters of the synapse model have
      been readjusted to better simulate reported physiological discharge rates at
      saturation for higher characteristic frequencies [Liberman, J. Acoust. Soc. Am.
      63, 442-455 (1978)]. This modification also corrects the responses of higher
      characteristic frequency (CF) model fibers to low-frequency tones that were
      erroneously much higher than the responses of low-CF model fibers in the previous
      version. In addition, an analytical method has been implemented to compute the
      mean discharge rate and variance from the model's synapse output that takes into
      account the effects of absolute refractoriness. 

PMID- 24437769
TI  - Characteristics of the 2f(1)-f(2) distortion product otoacoustic emission in a
      normal hearing population.
AB  - Distortion-product otoacoustic emission (DPOAE) fine structure and component
      characteristics are reported between 0.75 and 16 kHz in 356 clinically normal
      hearing human subjects ages 10 to 65 yr. Stimulus tones at 55/40, 65/55, and
      75/75 dB SPL were delivered using custom designed drivers and a calibration
      method that compensated for the depth of insertion of the otoacoustic emission
      (OAE) probe in the ear canal. DPOAE fine structure depth and spacing were found
      to be consistent with previous reports with depth varying between 3 and 7 dB and
      average spacing ratios (f/Deltaf) between 15 and 25 depending on stimulus level
      and frequency. In general, fine structure depth increased with increasing
      frequency, likely due to a diminishing difference between DPOAE component levels.
      Fine structure spacing became wider with increasing age above 8 kHz. DPOAE
      components were extracted using the inverse fast Fourier transform method,
      adhering to a strict signal to noise ratio criterion for clearer interpretation.
      Component data from four age groups between 18 and 55 yr old were available for
      the stimulus levels of 75/75 dB SPL. The age groups could be differentiated with
      greater than 90% accuracy when using the level of the component presumed to
      originate from the DPOAE characteristic frequency place. This accuracy held even
      for frequencies at and below 4 kHz where the age groups exhibited similar average
      hearing thresholds. 

PMID- 24437771
TI  - Plasticity and modified loudness following short-term unilateral deprivation:
      evidence of multiple gain mechanisms within the auditory system.
AB  - Auditory deprivation and stimulation can change the threshold of the acoustic
      middle ear reflex as well as loudness in adult listeners. However, it has
      remained unclear whether changes in these measures are due to the same mechanism.
      In this study, deprivation was achieved using a monaural earplug that was worn by
      listeners for 7 days. Acoustic reflex thresholds (ARTs) and categorical loudness
      ratings were measured using a blinded design in which the experimenter was
      unaware of which ear had been plugged. Immediately after terminating unilateral
      deprivation, ARTs were obtained at a lower sound pressure level in the ear that
      had been fitted with an earplug and at a higher sound pressure level in the
      control ear. In contrast, categorical judgments of loudness changed in the same
      direction in both ears with a given stimulus level reported as louder after
      unilateral deprivation. The relationship between changes to the ART and loudness
      judgments was not statistically significant. For both the ARTs and the
      categorical loudness judgments, most of the changes had disappeared within 24 h
      after earplug removal. The changes in ARTs, as a consequence of unilateral sound
      deprivation, are consistent with a gain control mechanism; however, the lack of
      relationship with the categorical loudness judgments, and the different pattern
      of findings for each measure, suggests the possibility of multiple gain
      mechanisms. 

PMID- 24437770
TI  - Spontaneous otoacoustic emissions, threshold microstructure, and psychophysical
      tuning over a wide frequency range in humans.
AB  - Hearing thresholds have been shown to exhibit periodic minima and maxima, a
      pattern known as threshold microstructure. Microstructure has previously been
      linked to spontaneous otoacoustic emissions (SOAEs) and normal cochlear function.
      However, SOAEs at high frequencies (>4 kHz) have been associated with hearing
      loss or cochlear pathology in some reports. Microstructure would not be expected
      near these high-frequency SOAEs. Psychophysical tuning curves (PTCs), the
      expression of frequency selectivity, may also be altered by SOAEs. Prior
      comparisons of tuning between ears with and without SOAEs demonstrated sharper
      tuning in ears with emissions. Here, threshold microstructure and PTCs were
      compared at SOAE frequencies ranging between 1.2 and 13.9 kHz using subjects
      without SOAEs as controls. Results indicate: (1) Threshold microstructure is
      observable in the vicinity of SOAEs of all frequencies; (2) PTCs are influenced
      by SOAEs, resulting in shifted tuning curve tips, multiple tips, or inversion.
      High frequency SOAEs show a greater effect on PTC morphology. The influence of
      most SOAEs at high frequencies on threshold microstructure and PTCs is consistent
      with those at lower frequencies, suggesting that high-frequency SOAEs reflect the
      same cochlear processes that lead to SOAEs at lower frequencies. 

PMID- 24437772
TI  - Effects of tonotopicity, adaptation, modulation tuning, and temporal coherence in
      "primitive" auditory stream segregation.
AB  - The perceptual organization of two-tone sequences into auditory streams was
      investigated using a modeling framework consisting of an auditory pre-processing
      front end [Dau et al., J. Acoust. Soc. Am. 102, 2892-2905 (1997)] combined with a
      temporal coherence-analysis back end [Elhilali et al., Neuron 61, 317-329
      (2009)]. Two experimental paradigms were considered: (i) Stream segregation as a
      function of tone repetition time (TRT) and frequency separation (Deltaf) and (ii)
      grouping of distant spectral components based on onset/offset synchrony. The
      simulated and experimental results of the present study supported the hypothesis
      that forward masking enhances the ability to perceptually segregate spectrally
      close tone sequences. Furthermore, the modeling suggested that effects of neural
      adaptation and processing though modulation-frequency selective filters may
      enhance the sensitivity to onset asynchrony of spectral components, facilitating
      the listeners' ability to segregate temporally overlapping sounds into separate
      auditory objects. Overall, the modeling framework may be useful to study the
      contributions of bottom-up auditory features on "primitive" grouping, also in
      more complex acoustic scenarios than those considered here. 

PMID- 24437773
TI  - Training improves cochlear implant rate discrimination on a psychophysical task.
AB  - The purpose of this study was to determine the extent to which cochlear implant
      (CI) rate discrimination can be improved through training. Six adult CI users
      took part in a study that included 32 h of training and assessment on rate
      discrimination measures. Rate difference limens (DLs) were measured from 110 to
      3520 Hz in octave steps using 500 ms biphasic pulse trains; the target and
      standard stimuli were loudness-balanced with the target always at an adaptively
      lower rate. DLs were measured at four electrode positions corresponding to basal,
      mid-basal, mid-apical, and apical locations. Procedural variations were
      implemented to determine if rate discrimination was impacted by random variations
      in stimulus amplitude or by amplitude modulation. DLs improved by more than a
      factor of 2 across subjects, electrodes, and standard rates. Factor analysis
      indicated that the effect of training was comparable for all electrodes and
      standard rates tested. Neither level roving nor amplitude modulation had a
      significant effect on rate DLs. In conclusion, the results demonstrate that
      training can significantly improve CI rate discrimination on a psychophysical
      task. 

PMID- 24437774
TI  - The effects of age and hearing loss on interaural phase difference
      discrimination.
AB  - The discrimination of interaural phase differences (IPDs) requires accurate
      binaural temporal processing and has been used as a measure of sensitivity to
      temporal envelope and temporal fine structure (TFS). Previous studies found that
      TFS-IPD discrimination declined with age and with sensorineural hearing loss
      (SNHL), but age and SNHL have often been confounded. The aim of this study was to
      determine the independent contributions of age and SNHL to TFS and envelope IPD
      discrimination by using a sample of adults with a wide range of ages and SNHL. A
      two-interval, two-alternative forced-choice procedure was used to measure IPD
      discrimination thresholds for 20-Hz amplitude-modulated tones with carrier
      frequencies of 250 or 500 Hz when the IPD was in either the stimulus envelope or
      TFS. There were positive correlations between absolute thresholds and TFS-IPD
      thresholds, but not envelope-IPD thresholds, when age was accounted for. This
      supports the idea that SNHL affects TFS processing independently to age. Age was
      positively correlated with envelope-IPD thresholds at both carrier frequencies
      and TFS-IPD thresholds at 500 Hz, when absolute thresholds were accounted for.
      These results suggest that age negatively affects the binaural processing of
      envelope and TFS at some frequencies independently of SNHL. 

PMID- 24437775
TI  - Tongue kinematics in palate relative coordinate spaces for electro-magnetic
      articulography.
AB  - This paper describes a method for constructing a three-dimensional model of the
      hard palate using electro-magnetic articulography, and defines two algorithms to
      derive constriction degree and constriction location values from the trajectories
      of tongue coils using this model. The kinematics of tongue motion that have been
      transformed into constriction degree and constriction location values are
      investigated in detail to determine whether this type of representation obeys the
      constraints theorized to operate over higher level motor control. Results show
      that palate-relative coordinate spaces decouple mechanical dependencies present
      in the tongue, while maintaining low-level kinematic properties. They
      additionally preserve the 1/3 power law for speed and curvature observed across
      many motor systems. Finally, it is shown that tongue movements in a palate
      relative coordinate space more closely correspond to their optimal, jerk
      minimized trajectories. These results suggest that this type of coordinate space
      provides a closer match to higher level motor-planning, in line with production
      models that specify control units in terms of vocal tract constriction
      parameters. 

PMID- 24437776
TI  - The accuracy of a voice vote.
AB  - The accuracy of a voice vote was addressed by systematically varying group size,
      individual voter loudness, and words that are typically used to express agreement
      or disagreement. Five judges rated the loudness of two competing groups in A-B
      comparison tasks. Acoustic analysis was performed to determine the sound energy
      level of each word uttered by each group. Results showed that individual voter
      differences in energy level can grossly alter group loudness and bias the vote.
      Unless some control is imposed on the sound level of individual voters, it is
      difficult to establish even a two-thirds majority, much less a simple majority.
      There is no symmetry in the bias created by unequal sound production of
      individuals. Soft voices do not bias the group loudness much, but loud voices do.
      The phonetic balance of the two words chosen (e.g., "yea" and "nay" as opposed to
      "aye" and "no") seems to be less of an issue. 

PMID- 24437777
TI  - Two-dimensional vocal tracts with three-dimensional behavior in the numerical
      generation of vowels.
AB  - Two-dimensional (2D) numerical simulations of vocal tract acoustics may provide a
      good balance between the high quality of three-dimensional (3D) finite element
      approaches and the low computational cost of one-dimensional (1D) techniques.
      However, 2D models are usually generated by considering the 2D vocal tract as a
      midsagittal cut of a 3D version, i.e., using the same radius function, wall
      impedance, glottal flow, and radiation losses as in 3D, which leads to strong
      discrepancies in the resulting vocal tract transfer functions. In this work, a
      four step methodology is proposed to match the behavior of 2D simulations with
      that of 3D vocal tracts with circular cross-sections. First, the 2D vocal tract
      profile becomes modified to tune the formant locations. Second, the 2D wall
      impedance is adjusted to fit the formant bandwidths. Third, the 2D glottal flow
      gets scaled to recover 3D pressure levels. Fourth and last, the 2D radiation
      model is tuned to match the 3D model following an optimization process. The
      procedure is tested for vowels /a/, /i/, and /u/ and the obtained results are
      compared with those of a full 3D simulation, a conventional 2D approach, and a 1D
      chain matrix model. 

PMID- 24437778
TI  - Intraglottal geometry and velocity measurements in canine larynges.
AB  - Previous flow velocity measurements during phonation in canine larynges were done
      above the glottal exit. These studies found that vortical structures are present
      in the flow above the glottis at different phases of the glottal cycle. Some
      vortices were observed to leave the glottis during the closing phase and
      assumptions were proposed regarding their formation mechanism. In the current
      study, intraglottal velocity measurements are performed using PIV, and the
      intraglottal flow characteristics are determined. Results from five canine
      larynges show that at low subglottal pressure the glottis assumes a minimal
      divergence angle during closing and the flow separates at the glottal exit.
      Vortical structures are observed above the glottis but not inside. As the
      subglottal pressure is increased, the divergence angle between the folds during
      closing increases and the location of the flow separation moves upstream into the
      glottis. Entrainment flow enters the glottis to fill the void that is formed
      between the glottal jet and the fold. Vortical structures develop near the
      superior edge at medium and high subglottal pressures from the flow separation.
      The magnitude of their swirling strength changes as a function of the wall
      dynamics. 

PMID- 24437779
TI  - Recognition memory in noise for speech of varying intelligibility.
AB  - This study investigated the extent to which noise impacts normal-hearing young
      adults' speech processing of sentences that vary in intelligibility.
      Intelligibility and recognition memory in noise were examined for conversational
      and clear speech sentences recorded in quiet (quiet speech, QS) and in response
      to the environmental noise (noise-adapted speech, NAS). Results showed that (1)
      increased intelligibility through conversational-to-clear speech modifications
      led to improved recognition memory and (2) NAS presented a more naturalistic
      speech adaptation to noise compared to QS, leading to more accurate word
      recognition and enhanced sentence recognition memory. These results demonstrate
      that acoustic-phonetic modifications implemented in listener-oriented speech
      enhance speech-in-noise processing beyond word recognition. Effortful speech
      processing in challenging listening environments can thus be improved by speaking
      style adaptations on the part of the talker. In addition to enhanced
      intelligibility, a substantial improvement in recognition memory can be achieved
      through speaker adaptations to the environment and to the listener when in
      adverse conditions. 

PMID- 24437780
TI  - Detection of high-frequency energy level changes in speech and singing.
AB  - Previous work has shown that human listeners are sensitive to level differences
      in high-frequency energy (HFE) in isolated vowel sounds produced by male singers.
      Results indicated that sensitivity to HFE level changes increased with overall
      HFE level, suggesting that listeners would be more "tuned" to HFE in vocal
      production exhibiting higher levels of HFE. It follows that sensitivity to HFE
      level changes should be higher (1) for female vocal production than for male
      vocal production and (2) for singing than for speech. To test this hypothesis,
      difference limens for HFE level changes in male and female speech and singing
      were obtained. Listeners showed significantly greater ability to detect level
      changes in singing vs speech but not in female vs male speech. Mean differences
      limen scores for speech and singing were about 5 dB in the 8-kHz octave (5.6-11.3
      kHz) but 8-10 dB in the 16-kHz octave (11.3-22 kHz). These scores are lower
      (better) than those previously reported for isolated vowels and some musical
      instruments. 

PMID- 24437781
TI  - A Danish open-set speech corpus for competing-speech studies.
AB  - Studies investigating speech-on-speech masking effects commonly use closed-set
      speech materials such as the coordinate response measure [Bolia et al. (2000). J.
      Acoust. Soc. Am. 107, 1065-1066]. However, these studies typically result in very
      low (i.e., negative) speech recognition thresholds (SRTs) when the competing
      speech signals are spatially separated. To achieve higher SRTs that correspond
      more closely to natural communication situations, an open-set, low-context, multi
      talker speech corpus was developed. Three sets of 268 unique Danish sentences
      were created, and each set was recorded with one of three professional female
      talkers. The intelligibility of each sentence in the presence of speech-shaped
      noise was measured. For each talker, 200 approximately equally intelligible
      sentences were then selected and systematically distributed into 10 test lists.
      Test list homogeneity was assessed in a setup with a frontal target sentence and
      two concurrent masker sentences at +/-50 degrees  azimuth. For a group of 16
      normal-hearing listeners and a group of 15 elderly (linearly aided) hearing
      impaired listeners, overall SRTs of, respectively, +1.3 dB and +6.3 dB target-to
      masker ratio were obtained. The new corpus was found to be very sensitive to
      inter-individual differences and produced consistent results across test lists.
      The corpus is publicly available. 

PMID- 24437782
TI  - Characterizing the distribution of the quadrilateral vowel space area.
AB  - The vowel space area (VSA) has been studied as a quantitative index of
      intelligibility to the extent it captures articulatory working space and
      reductions therein. The majority of such studies have been empirical wherein
      measures of VSA are correlated with perceptual measures of intelligibility.
      However, the literature contains minimal mathematical analysis of the properties
      of this metric. This paper further develops the theoretical underpinnings of this
      metric by presenting a detailed analysis of the statistical properties of the VSA
      and characterizing its distribution through the moment generating function. The
      theoretical analysis is confirmed by a series of experiments where empirically
      estimated and theoretically predicted statistics of this function are compared.
      The results show that on the Hillenbrand and TIMIT data, the theoretically
      predicted values of the higher-order statistics of the VSA match very well with
      the empirical estimates of the same. 

PMID- 24437784
TI  - Effects of noise suppression on intelligibility. II: An attempt to validate
      physical metrics.
AB  - Using the data presented in the accompanying paper [Hilkhuysen et al., J. Acoust.
      Soc. Am. 131, 531-539 (2012)], the ability of six metrics to predict
      intelligibility of speech in noise before and after noise suppression was
      studied. The metrics considered were the Speech Intelligibility Index (SII), the
      fractional Articulation Index (fAI), the coherence intelligibility index based on
      the mid-levels in speech (CSIImid), an extension of the Normalized Coherence
      Metric (NCM+), a part of the speech-based envelope power model (pre-sEPSM), and
      the Short Term Objective Intelligibility measure (STOI). Three of the measures,
      SII, CSIImid, and NCM+, overpredicted intelligibility after noise reduction,
      whereas fAI underpredicted these intelligibilities. The pre-sEPSM metric worked
      well for speech in babble but failed with car noise. STOI gave the best
      predictions, but overall the size of intelligibility prediction errors were
      greater than the change in intelligibility caused by noise suppression.
      Suggestions for improvements of the metrics are discussed. 

PMID- 24437783
TI  - Contribution of low-frequency harmonics to Mandarin Chinese tone identification
      in quiet and six-talker babble background.
AB  - The goal of this study was to investigate Mandarin Chinese tone identification in
      quiet and multi-talker babble conditions for normal-hearing listeners. Tone
      identification was measured with speech stimuli and stimuli with low and/or high
      harmonics that were embedded in three Mandarin vowels with two fundamental
      frequencies. There were six types of stimuli: all harmonics (All), low harmonics
      (Low), high harmonics (High), and the first (H1), second (H2), and third (H3)
      harmonic. Results showed that, for quiet conditions, individual harmonics carried
      frequency contour information well enough for tone identification with high
      accuracy; however, in noisy conditions, tone identification with individual low
      harmonics (e.g., H1, H2, and H3) was significantly lower than that with the Low,
      High, and All harmonics. Moreover, tone identification with individual harmonics
      in noise was lower for a low F0 than for a high F0, and was also dependent on
      vowel category. Tone identification with individual low-frequency harmonics was
      accounted for by local signal-to-noise ratios, indicating that audibility of
      harmonics in noise may play a primary role in tone identification. 

PMID- 24437785
TI  - Speech enhancement using empirical mode decomposition and the Teager-Kaiser
      energy operator.
AB  - In this paper a speech denoising strategy based on time adaptive thresholding of
      intrinsic modes functions (IMFs) of the signal, extracted by empirical mode
      decomposition (EMD), is introduced. The denoised signal is reconstructed by the
      superposition of its adaptive thresholded IMFs. Adaptive thresholds are estimated
      using the Teager-Kaiser energy operator (TKEO) of signal IMFs. More precisely,
      TKEO identifies the type of frame by expanding differences between speech and non
      speech frames in each IMF. Based on the EMD, the proposed speech denoising scheme
      is a fully data-driven approach. The method is tested on speech signals with
      different noise levels and the results are compared to EMD-shrinkage and wavelet
      transform (WT) coupled with TKEO. Speech enhancement performance is evaluated
      using output signal to noise ratio (SNR) and perceptual evaluation of speech
      quality (PESQ) measure. Based on the analyzed speech signals, the proposed
      enhancement scheme performs better than WT-TKEO and EMD-shrinkage approaches in
      terms of output SNR and PESQ. The noise is greatly reduced using time-adaptive
      thresholding than universal thresholding. The study is limited to signals
      corrupted by additive white Gaussian noise. 

PMID- 24437786
TI  - Detection of the closure-burst transitions of stops and affricates in continuous
      speech using the plosion index.
AB  - Automatic and accurate detection of the closure-burst transition events of stops
      and affricates serves many applications in speech processing. A temporal measure
      named the plosion index is proposed to detect such events, which are
      characterized by an abrupt increase in energy. Using the maxima of the pitch
      synchronous normalized cross correlation as an additional temporal feature, a
      rule-based algorithm is designed that aims at selecting only those events
      associated with the closure-burst transitions of stops and affricates. The
      performance of the algorithm, characterized by receiver operating characteristic
      curves and temporal accuracy, is evaluated using the labeled closure-burst
      transitions of stops and affricates of the entire TIMIT test and training
      databases. The robustness of the algorithm is studied with respect to global
      white and babble noise as well as local noise using the TIMIT test set and on
      telephone quality speech using the NTIMIT test set. For these experiments, the
      proposed algorithm, which does not require explicit statistical training and is
      based on two one-dimensional temporal measures, gives a performance comparable to
      or better than the state-of-the-art methods. In addition, to test the
      scalability, the algorithm is applied on the Buckeye conversational speech corpus
      and databases of two Indian languages. 

PMID- 24437787
TI  - The effect of nearby timpani strokes on horn playing.
AB  - Horn players have observed that timpani strokes can interfere disruptively with
      their playing, especially when they are seated close to the timpani. Measuring
      the horn's transfer function in the bell-to-mouthpiece direction reveals that the
      horn behaves as an acoustic impedance matching device, capable of transmitting
      waves with pressure gains of at least 20 dB near horn playing resonances. During
      moderate to loud timpani strokes, the horn transmits an overall impulse gain
      response of at least 16 dB from the bell to the mouthpiece, while evidence of non
      linear bore propagation can be observed for louder strokes. If the timpani is
      tuned near a horn resonance, as is usually the case, further bore resonance
      interactions may be observed leading to gains of ~26 dB from bell to mouthpiece.
      Finally, measurements of horn playing made under conditions approximating playing
      reveal that timpani strokes sounding near the horn bell are capable of disrupting
      horn playing by affecting the amplitude, periodicity, and frequency of the
      pressure signal generated at the horn player's lips. 

PMID- 24437788
TI  - Response of an artificially blown clarinet to different blowing pressure
      profiles.
AB  - Using an artificial mouth with an accurate pressure control, the onset of the
      pressure oscillations inside the mouthpiece of a simplified clarinet is studied
      experimentally. Two time profiles are used for the blowing pressure: in a first
      set of experiments the pressure is increased at constant rates, then decreased at
      the same rate. In a second set of experiments the pressure rises at a constant
      rate and is then kept constant for an arbitrary period of time. In both cases the
      experiments are repeated for different increase rates. Numerical simulations
      using a simplified clarinet model blown with a constantly increasing mouth
      pressure are compared to the oscillating pressure obtained inside the mouthpiece.
      Both show that the beginning of the oscillations appears at a higher pressure
      values than the theoretical static threshold pressure, a manifestation of
      bifurcation delay. Experiments performed using an interrupted increase in mouth
      pressure show that the beginning of the oscillation occurs close to the stop in
      the increase of the pressure. Experimental results also highlight that the speed
      of the onset transient of the sound is roughly the same, independently of the
      duration of the increase phase of the blowing pressure. 

PMID- 24437789
TI  - Vocal tract resonances in singing: variation with laryngeal mechanism for male
      operatic singers in chest and falsetto registers.
AB  - Seven male operatic singers sang the same notes and vowels in their chest and
      their falsetto registers, covering the overlap frequency range where two main
      laryngeal mechanisms can be identified by means of electroglottography: M1 in
      chest register and M2 in falsetto register. Glottal contact quotients determined
      using electroglottography were typically lower by 0.27 in M2 than in M1. Vocal
      tract resonance frequencies were measured by using broadband excitation at the
      lips and found to be typically lower in M2 than in M1 sung at the same pitch and
      vowel; R1 typically by 65 Hz and R2 by 90 Hz. These shifts in tract resonances
      were only weakly correlated with the changes in the contact quotient or laryngeal
      height that were measured simultaneously. There was considerable variability in
      the resonance tuning strategies used by the singers, and no evidence of a uniform
      systematic tuning strategy used by all singers. A simple model estimates that the
      shifts in resonance frequencies are consistent with the effective glottal area in
      falsetto register (M2) being 60%-70% of its value in chest register (M1). 

PMID- 24437790
TI  - Combining whistle acoustic parameters to discriminate Mediterranean odontocetes
      during passive acoustic monitoring.
AB  - Acoustic observation can complement visual observation to more effectively
      monitor occurrence and distribution of marine mammals. For effective acoustic
      censuses, calibration methods must be determined by joint visual and acoustic
      studies. Research is still needed in the field of acoustic species
      identification, particularly for smaller odontocetes. From 1994 to 2012, whistles
      of four odontocete species were recorded in different areas of the Mediterranean
      Sea to determine how reliably these vocalizations can be classified to species.
      Recordings were attributed to species by simultaneous visual observation. The
      results of this study highlight that the frequency parameters, which are linked
      to physical features of animals, show lower variability than modulation
      parameters, which are likely to be more dependent on complex eco-ethological
      contexts. For all the studied species, minimum and maximum frequencies were
      linearly correlated with body size. DFA and Classification Tree Analysis (CART)
      show that these parameters were the most important for classifying species;
      however, both statistical methods highlighted the need for combining them with
      the number of contour minima and contour maxima for correct classification.
      Generally, DFA and CART results reflected both phylogenetic distance (especially
      for common and striped dolphins) and the size of the species. 

PMID- 24437791
TI  - High resolution acoustic measurement system and beam pattern reconstruction
      method for bat echolocation emissions.
AB  - Measurements of the transmit beam patterns emitted by echolocating bats have
      previously been limited to cross-sectional planes or averaged over multiple
      signals using sparse microphone arrays. To date, no high-resolution measurements
      of individual bat transmit beams have been reported in the literature. Recent
      studies indicate that bats may change the time-frequency structure of their calls
      depending on the task, and suggest that their beam patterns are more dynamic than
      previously thought. To investigate beam pattern dynamics in a variety of bat
      species, a high-density reconfigurable microphone array was designed and
      constructed using low-cost ultrasonic microphones and custom electronic
      circuitry. The planar array is 1.83 m wide by 1.42 m tall with microphones
      positioned on a 2.54 cm square grid. The system can capture up to 228 channels
      simultaneously at a 500 kHz sampling rate. Beam patterns are reconstructed in
      azimuth, elevation, and frequency for visualization and further analysis.
      Validation of the array measurement system and post-processing functions is shown
      by reconstructing the beam pattern of a transducer with a fixed circular aperture
      and comparing the result with a theoretical model. To demonstrate the system in
      use, transmit beam patterns of the big brown bat, Eptesicus fuscus, are shown. 

PMID- 24437792
TI  - Presence and seasonal variation of deep diving foraging odontocetes around Kauai,
      Hawaii using remote autonomous acoustic recorders.
AB  - Ecological acoustic recorders (EARs) were moored off the bottom in relatively
      deep depths (609-710 m) at five locations around the island of Kauai. Initially,
      the EARs had an analog-to-digital sample rate of 64 kHz with 30-s recordings
      every 5 min. After the second deployment the sampling rate was increased to 80
      kHz in order to better record beaked whale biosonar signals. The results of the
      80 kHz recording are discussed in this manuscript and are the results of three
      deployments over a year's period (January 2010 to January 2011). Five categories
      of the biosonar signal detection of deep diving odontocetes were created, short
      finned pilot whales, sperm whales, beaked whales, Risso's dolphins, and unknown
      dolphins. During any given day, at least one species of these deep diving
      odontocetes were detected. On many days, several species were detected. The
      biosonar signals of short-finned pilot whales were detected the most often with
      approximately 30% of all the signals, followed by beaked and sperm whales
      approximately 22% and 21% of all clicks, respectively. The seasonal patterns were
      not very strong except in the SW location with distinct peak in detection during
      the months of April-June 2010 period. 

PMID- 24437793
TI  - Hearing threshold measurements of five stranded short-finned pilot whales
      (Globicephala macrorhynchus).
AB  - On May 5, 2011, 23 short-finned pilot whales, Globicephala macrorhynchus, were
      stranded along the coastline near Cudjoe Key, FL. Five animals (two adult
      females, two juvenile females, and an adult male) were transported to a
      rehabilitation facility in Key Largo, FL. Auditory evoked potentials (AEPs) were
      recorded in response to amplitude modulated tone pips modulated at 1000 Hz. AEP
      thresholds were determined at 10, 20, 40, 80, and 120 kHz for the four females.
      However, the adult male was euthanized prior to testing. Short-finned pilot
      whales had peak sensitivity at lower frequencies than other odontocetes such as
      bottlenose dolphins. Greatest sensitivity was around 40 kHz for all whales, while
      thresholds for the two adult females were 25-61 dB higher at 80 kHz than the
      juveniles. Click evoked potentials were similar between the four whales and
      comparable to other echolocating odontocetes. Click evoked potential data from a
      fifth short-finned pilot whale that had stranded in Curacao showed no response.
      These findings add to the limited database of pilot whale (short- and long
      finned) hearing studies, of which there are only two others [Schlundt et al.
      (2011). J. Acoust. Soc. Am. 129, 1111-1116 and Pacini et al. (2010). J. Exp.
      Biol. 213, 3138-3143]. 

PMID- 24437850
TI  - Clutter depth discrimination using the wavenumber spectrum.
AB  - Clutter depth is a key parameter in mid-frequency active sonar systems to
      discriminate between sources of clutter and targets of interest. A method is
      needed to remotely discriminate clutter depth by information contained in the
      backscattered signal-without a priori knowledge of that depth. Presented here is
      an efficient approach for clutter depth estimation using the structure in the
      wavenumber spectrum. Based on numerical simulations for a simple test case in a
      shallow water waveguide, this technique demonstrates the potential capability to
      discriminate between a clutter source in the water column vs one on the seabed. 

PMID- 24437794
TI  - Acceleration of ultrasound thermal therapy by patterned acoustic droplet
      vaporization.
AB  - One application of acoustic droplet vaporization (ADV), a method of converting
      biocompatible microdroplets into microbubbles, is to enhance locally high
      intensity focused ultrasound (HIFU) therapy. Two objectives are pursued here: (1)
      the controlled creation of a bubble trench prior to HIFU using ADV and (2) use of
      the trench for increasing ablation volumes, lowering acoustic powers, and
      decreasing therapy duration. Thermally responsive phantoms were made with
      perfluorocarbon emulsion. Compound lesions were formed in a laboratory setting
      and a clinical magnetic resonance imaging (MRI)-guided HIFU system. Linear and
      spiral patterned compound lesions were generated in trenches. A larger fraction
      of the HIFU beam is contained to increase the generation of heat. Using the
      laboratory system, a 90 mm linear length spiral trench was formed in 30 s with
      mechanical beam steering. Comparatively, the clinical HIFU system formed a 19.9
      mm linear length spiral trench in approximately 1 s with electronic beam
      steering. Lesions were imaged optically and with MRI. A uniform thermal ablation
      volume of 3.25 mL was achieved in 55.4 s (4-times faster than standard clinical
      HIFU and 14-times larger volume versus sum of individual lesions). Single lesions
      showed a 400% volume increase. 

PMID- 24437852
TI  - Effects of early and late reflections on intelligibility of reverberated speech
      by cochlear implant listeners.
AB  - The purpose of this study was to determine the overall impact of early and late
      reflections on the intelligibility of reverberated speech by cochlear implant
      listeners. Two specific reverberation times were assessed. For each reverberation
      time, sentences were presented in three different conditions wherein the target
      signal was filtered through the early, late or entire part of the acoustic
      impulse response. Results obtained with seven cochlear implant listeners
      indicated that while early reflections neither enhanced nor reduced overall
      speech perception performance, late reflections severely reduced speech
      intelligibility in both reverberant conditions tested. 

PMID- 24437851
TI  - Accurate measurement of guided modes in a plate using a bidirectional approach.
AB  - Measuring guided wave propagation in long bones is of interest to the medical
      community. When an inclination exists between the probe and the tested specimen
      surface, a bias is introduced on the guided mode wavenumbers. The aim of this
      study was to generalize the bidirectional axial transmission technique initially
      developed for the first arriving signal. Validation tests were performed on
      academic materials such a bone-mimicking plate covered with either a silicon or
      fat-mimicking layer. For any inclination, the wavenumbers measured with the probe
      parallel to the waveguide surface can be obtained by averaging the wavenumbers
      measured in two opposite directions. 

PMID- 24437853
TI  - Augmented warning sound detection for hearing protectors.
AB  - Perception of warning sounds, such as vehicle backup alarms, is reduced when
      hearing protection devices (HPDs) are worn. A cross-correlation approach is
      employed to detect a pre-selected warning sound and enable it to bypass the
      attenuation of the HPD while still attenuating the environmental noise. Computer
      simulation shows that the algorithm can detect the specified alarm at signal-to
      environmental-noise ratios as low as -30 dB. Human subject testing of the
      algorithm, implemented on a modified commercial HPD, confirms the minimum
      detection threshold obtained in simulation, and demonstrates a 7 dB improvement
      in detection threshold compared with the unmodified HPD. 

PMID- 24437854
TI  - Marine mammal audibility of selected shallow-water survey sources.
AB  - Most attention about the acoustic effects of marine survey sound sources on
      marine mammals has focused on airgun arrays, with other common sources receiving
      less scrutiny. Sound levels above hearing threshold (sensation levels) were
      modeled for six marine mammal species and seven different survey sources in
      shallow water. The model indicated that odontocetes were most likely to hear
      sounds from mid-frequency sources (fishery, communication, and hydrographic
      systems), mysticetes from low-frequency sources (sub-bottom profiler and
      airguns), and pinnipeds from both mid- and low-frequency sources. High-frequency
      sources (side-scan and multibeam) generated the lowest estimated sensation levels
      for all marine mammal species groups. 

PMID- 24437855
TI  - Design and outcomes of an acoustic data visualization seminar.
AB  - Recently, the Department of Media Technology at Aalto University offered a
      seminar entitled Applied Data Analysis and Visualization. The course used spatial
      impulse response measurements from concert halls as the context to explore high
      dimensional data visualization methods. Students were encouraged to represent
      source and receiver positions, spatial aspects, and temporal development of sound
      fields, frequency characteristics, and comparisons between halls, using
      animations and interactive graphics. The primary learning objectives were for the
      students to translate their skills across disciplines and gain a working
      understanding of high-dimensional data visualization techniques. Accompanying
      files present examples of student-generated, animated and interactive
      visualizations. 

PMID- 24437856
TI  - Binaural advantages in users of bimodal and bilateral cochlear implant devices.
AB  - This paper investigates to what extent users of bilateral and bimodal fittings
      should expect to benefit from all three different binaural advantages found to be
      present in normal-hearing listeners. Head-shadow and binaural squelch are
      advantages occurring under spatially separated speech and noise, while summation
      emerges when speech and noise coincide in space. For 14 bilateral or bimodal
      listeners, speech reception thresholds in the presence of four-talker babble were
      measured in sound-field under various speech and noise configurations.
      Statistical analysis revealed significant advantages of head-shadow and summation
      for both bilateral and bimodal listeners. Squelch was significant only for
      bimodal listeners. 

PMID- 24437857
TI  - Contour identification with pitch and loudness cues using cochlear implants.
AB  - Different from speech, pitch and loudness cues may or may not co-vary in music.
      Cochlear implant (CI) users with poor pitch perception may use loudness contour
      cues more than normal-hearing (NH) listeners. Contour identification was tested
      in CI users and NH listeners; the five-note contours contained either pitch cues
      alone, loudness cues alone, or both. Results showed that NH listeners' contour
      identification was better with pitch cues than with loudness cues; CI users
      performed similarly with either cues. When pitch and loudness cues were co
      varied, CI performance significantly improved, suggesting that CI users were able
      to integrate the two cues. 

PMID- 24437858
TI  - Perspective: structural dynamics in condensed matter mapped by femtosecond x-ray
      diffraction.
AB  - Ultrashort soft and hard x-ray pulses are sensitive probes of structural dynamics
      on the picometer length and femtosecond time scales of electronic and atomic
      motions. Recent progress in generating such pulses has initiated new directions
      of condensed matter research, exploiting a variety of x-ray absorption,
      scattering, and diffraction methods to probe photoinduced structural dynamics.
      Atomic motion, changes of local structure and long-range order, as well as
      correlated electron motion and charge transfer have been resolved in space and
      time, providing a most direct access to the physical mechanisms and interactions
      driving reversible and irreversible changes of structure. This perspective
      combines an overview of recent advances in femtosecond x-ray diffraction with a
      discussion on ongoing and future developments. 

PMID- 24437859
TI  - Excitation energies with linear response density matrix functional theory along
      the dissociation coordinate of an electron-pair bond in N-electron systems.
AB  - Time dependent density matrix functional theory in its adiabatic linear response
      formulation delivers exact excitation energies omegaalpha and oscillator
      strengths falpha for two-electron systems if extended to the so-called phase
      including natural orbital (PINO) theory. The Lowdin-Shull expression for the
      energy of two-electron systems in terms of the natural orbitals and their phases
      affords in this case an exact phase-including natural orbital functional (PILS),
      which is non-primitive (contains other than just J and K integrals). In this
      paper, the extension of the PILS functional to N-electron systems is
      investigated. With the example of an elementary primitive NO functional (BBC1) it
      is shown that current density matrix functional theory ground state functionals,
      which were designed to produce decent approximations to the total energy, fail to
      deliver a qualitatively correct structure of the (inverse) response function, due
      to essential deficiencies in the reconstruction of the two-body reduced density
      matrix (2RDM). We now deduce essential features of an N-electron functional from
      a wavefunction Ansatz: The extension of the two-electron Lowdin-Shull
      wavefunction to the N-electron case informs about the phase information. In this
      paper, applications of this extended Lowdin-Shull (ELS) functional are considered
      for the simplest case, ELS(1): one (dissociating) two-electron bond in the field
      of occupied (including core) orbitals. ELS(1) produces high quality omegaalpha(R)
      curves along the bond dissociation coordinate R for the molecules LiH, Li2, and
      BH with the two outer valence electrons correlated. All of these results indicate
      that response properties are much more sensitive to deficiencies in the
      reconstruction of the 2RDM than the ground state energy, since derivatives of the
      functional with respect to both the NOs and the occupation numbers need to be
      accurate. 

PMID- 24437860
TI  - Analysis of and remedies for unphysical ground states of the multireference
      averaged coupled-pair functional.
AB  - A Multireference Configuration Interaction (MRCI) wavefunction includes both
      static and dynamic electron correlation. MRCI's well-known flaw, a lack of size
      extensivity, can be ameliorated with the Multireference Averaged Coupled-Pair
      Functional (MRACPF). However, the original MRACPF is frequently unstable,
      sometimes producing unphysical results. The more Multireference Averaged
      Quadratic Coupled-Cluster and MRACPF2 functionals also occasionally exhibit
      unphysical behavior. We find that these instabilities are avoided crossings with
      unphysical solutions to the MRACPF equations. We present two approaches to avoid
      the undesirable unphysical solutions. 

PMID- 24437861
TI  - Nuclear quadrupole moment-induced Cotton-Mouton effect in molecules.
AB  - Nuclear magneto-optic effects could make important contributions to novel, high
      sensitivity, and high-resolution spectroscopic and imaging methods that provide
      nuclear site-specific structural and dynamic information on molecular and
      materials systems. Here we present a first-principles electronic structure
      formulation of nuclear quadrupole moment-induced Cotton-Mouton effect in terms of
      response theory, as well as ab initio and density-functional theory calculations
      of this phenomenon for a series of molecular liquids: H2O, CH3NO2, CH3CH2OH,
      C6H6, C6H12 (cyclohexane), HI, XeF2, WF5Cl, and Pt(C2dtp)2. The roles of basis
      set convergence, electron correlation, and relativistic effects are discussed.
      The estimated order of magnitude of the overall ellipticities induced to linearly
      polarized light is 10(-3)-10(-7) rad/(M cm) for fully spin polarized nuclei. The
      cases with the largest presently obtained ellipticities should be detectable with
      modern instrumentation in the Voigt magneto-optic setup, particularly for the
      heavy nuclei. 

PMID- 24437862
TI  - A method for analyzing the non-stationary nucleation and overall transition
      kinetics: a case of water.
AB  - We present the statistical method as a direct extension of the mean first-passage
      time concept to the analysis of molecular dynamics simulation data of a phase
      transformation. According to the method, the mean first-passage time trajectories
      for the first (i = 1) as well as for the subsequent (i = 2, 3, 4,[ellipsis
      (horizontal)]) nucleation events should be extracted that allows one to calculate
      the time-dependent nucleation rate, the critical value of the order parameter
      (the critical size), the waiting times for the nucleation events, and the growth
      law of the nuclei - i.e., all the terms, which are usually necessary to
      characterize the overall transition kinetics. There are no restrictions in the
      application of the method by the specific thermodynamic regions; and the
      nucleation rate parameters are extracted according to their basic definitions.
      The method differs from the Wedekind-Bartell scheme and its modification [A. V.
      Mokshin and B. N. Galimzyanov, J. Phys. Chem. B 116, 11959 (2012)], where the
      passage-times for the first (largest) nucleus are evaluated only and where the
      average waiting time for the first nucleation event is accessible instead of the
      true steady-state nucleation time scale. We demonstrate an efficiency of the
      method by its application to the analysis of the vapor-to-liquid transition
      kinetics in water at the different temperatures. The nucleation rate/time
      characteristics and the droplet growth parameters are computed on the basis of
      the coarse-grained molecular dynamics simulation data. 

PMID- 24437863
TI  - Multilevel summation for dispersion: a linear-time algorithm for r(-6)
      potentials.
AB  - We have extended the multilevel summation (MLS) method, originally developed to
      evaluate long-range Coulombic interactions in molecular dynamics simulations [R.
      D. Skeel, I. Tezcan, and D. J. Hardy, J. Comput. Chem. 23, 673 (2002)], to handle
      dispersion interactions. While dispersion potentials are formally short-ranged,
      accurate calculation of forces and energies in interfacial and inhomogeneous
      systems require long-range methods. The MLS method offers some significant
      advantages compared to the particle-particle particle-mesh and smooth particle
      mesh Ewald methods. Unlike mesh-based Ewald methods, MLS does not use fast
      Fourier transforms and is thus not limited by communication and bandwidth
      concerns. In addition, it scales linearly in the number of particles, as compared
      with the O(NlogN) complexity of the mesh-based Ewald methods. While the structure
      of the MLS method is invariant for different potentials, every algorithmic step
      had to be adapted to accommodate the r(-6) form of the dispersion interactions.
      In addition, we have derived error bounds, similar to those obtained by Hardy
      ["Multilevel summation for the fast evaluation of forces for the simulation of
      biomolecules," Ph.D. thesis, University of Illinois at Urbana-Champaign, 2006]
      for the electrostatic MLS. Using a prototype implementation, we have demonstrated
      the linear scaling of the MLS method for dispersion, and present results
      establishing the accuracy and efficiency of the method. 

PMID- 24437864
TI  - Numerical approach to unbiased and driven generalized elastic model.
AB  - From scaling arguments and numerical simulations, we investigate the properties
      of the generalized elastic model (GEM) that is used to describe various physical
      systems such as polymers, membranes, single-file systems, or rough interfaces. We
      compare analytical and numerical results for the subdiffusion exponent beta
      characterizing the growth of the mean squared displacement <(deltah)(2)> of the
      field h described by the GEM dynamic equation. We study the scaling properties of
      the qth order moments <?deltah?(q)> with time, finding that the interface
      fluctuations show no intermittent behavior. We also investigate the ergodic
      properties of the process h in terms of the ergodicity breaking parameter and the
      distribution of the time averaged mean squared displacement. Finally, we study
      numerically the driven GEM with a constant, localized perturbation and extract
      the characteristics of the average drift for a tagged probe. 

PMID- 24437865
TI  - Imaginary time correlations and the phaseless auxiliary field quantum Monte
      Carlo.
AB  - The phaseless Auxiliary Field Quantum Monte Carlo (AFQMC) method provides a well
      established approximation scheme for accurate calculations of ground state
      energies of many-fermions systems. Here we address the possibility of calculating
      imaginary time correlation functions with the phaseless AFQMC. We give a detailed
      description of the technique and test the quality of the results for static
      properties and imaginary time correlation functions against exact values for
      small systems. 

PMID- 24437866
TI  - Linear response theory for the density matrix renormalization group: efficient
      algorithms for strongly correlated excited states.
AB  - Linear response theory for the density matrix renormalization group (DMRG-LRT)
      was first presented in terms of the DMRG renormalization projectors [J. J.
      Dorando, J. Hachmann, and G. K.-L. Chan, J. Chem. Phys. 130, 184111 (2009)].
      Later, with an understanding of the manifold structure of the matrix product
      state (MPS) ansatz, which lies at the basis of the DMRG algorithm, a way was
      found to construct the linear response space for general choices of the MPS gauge
      in terms of the tangent space vectors [J. Haegeman, J. I. Cirac, T. J. Osborne,
      I. Pizorn, H. Verschelde, and F. Verstraete, Phys. Rev. Lett. 107, 070601
      (2011)]. These two developments led to the formulation of the Tamm-Dancoff and
      random phase approximations (TDA and RPA) for MPS. This work describes how these
      LRTs may be efficiently implemented through minor modifications of the DMRG sweep
      algorithm, at a computational cost which scales the same as the ground-state DMRG
      algorithm. In fact, the mixed canonical MPS form implicit to the DMRG sweep is
      essential for efficient implementation of the RPA, due to the structure of the
      second-order tangent space. We present ab initio DMRG-TDA results for excited
      states of polyenes, the water molecule, and a [2Fe-2S] iron-sulfur cluster. 

PMID- 24437867
TI  - Dissecting molecular descriptors into atomic contributions in density functional
      reactivity theory.
AB  - Density functional reactivity theory (DFRT) employs the electron density of a
      molecule and its related quantities such as gradient and Laplacian to describe
      its structure and reactivity properties. Proper descriptions at both molecular
      (global) and atomic (local) levels are equally important and illuminating. In
      this work, we make use of Bader's zero-flux partition scheme and consider atomic
      contributions for a few global reactivity descriptors in DFRT, including the
      density-based quantification of steric effect and related indices. Earlier, we
      proved that these quantities are intrinsically correlated for atomic and
      molecular systems [S. B. Liu, J. Chem. Phys. 126, 191107 (2007); ibid. 126,
      244103 (2007)]. In this work, a new basin-based integration algorithm has been
      implemented, whose reliability and effectiveness have been extensively examined.
      We also investigated a list of simple hydrocarbon systems and different scenarios
      of bonding processes, including stretching, bending, and rotating. Interesting
      changing patterns for the atomic and molecular values of these quantities have
      been revealed for different systems. This work not only confirms the strong
      correlation between these global reactivity descriptors for molecular systems, as
      theoretically proven earlier by us, it also provides new and unexpected changing
      patterns for their atomic values, which can be employed to understand the origin
      and nature of chemical phenomena. 

PMID- 24437868
TI  - Electron transfer in a two-level system within a Cole-Davidson vitreous bath.
AB  - We study electron transfer (ET) in a two level quantum system coupled to a glassy
      viscous bath. The bath is modeled by the Cole-Davidson (CD) spectral density. The
      ET in this model is compared to the ET in a normal Drude-Debye (DD) model. It is
      shown that at low temperatures and when the coupling to the bath is weak, the
      viscous bath preserves the quantum coherence for a longer time. However in the
      strong coupling regime, the tunneling rate is higher in the CD. In the classical
      high temperature limit the difference between the CD and DD models is negligible.

PMID- 24437869
TI  - Stochastic, real-space, imaginary-time evaluation of third-order Feynman
      Goldstone diagrams.
AB  - A new, alternative set of interpretation rules of Feynman-Goldstone diagrams for
      many-body perturbation theory is proposed, which translates diagrams into
      algebraic expressions suitable for direct Monte Carlo integrations. A vertex of a
      diagram is associated with a Coulomb interaction (rather than a two-electron
      integral) and an edge with the trace of a Green's function in real space and
      imaginary time. With these, 12 diagrams of third-order many-body perturbation
      (MP3) theory are converted into 20-dimensional integrals, which are then
      evaluated by a Monte Carlo method. It uses redundant walkers for convergence
      acceleration and a weight function for importance sampling in conjunction with
      the Metropolis algorithm. The resulting Monte Carlo MP3 method has low-rank
      polynomial size dependence of the operation cost, a negligible memory cost, and a
      naturally parallel computational kernel, while reproducing the correct
      correlation energies of small molecules within a few mEh after 10(6) Monte Carlo
      steps. 

PMID- 24437870
TI  - Fitting coupled potential energy surfaces for large systems: method and
      construction of a 3-state representation for phenol photodissociation in the full
      33 internal degrees of freedom using multireference configuration interaction
      determined data.
AB  - A recently reported algorithm for representing adiabatic states coupled by
      conical intersections using a quasi-diabatic state Hamiltonian in four and five
      atom systems is extended to treat nonadiabatic processes in considerably larger
      molecules. The method treats all internal degrees of freedom and uses electronic
      structure data from ab initio multireference configuration interaction wave
      functions with nuclear configuration selection based on quasi-classical surface
      hopping trajectories. The method is shown here to be able to treat ~30 internal
      degrees of freedom including dissociative and large amplitude internal motion.
      Two procedures are introduced which are essential to the algorithm, a null space
      projector which removes basis functions from the fitting process until they are
      needed and a partial diagonalization technique which allows for automated, but
      accurate, treatment of the vicinity of extended seams of conical intersections of
      two or more states. These procedures are described in detail. The method is
      illustrated using the photodissociaton of phenol, C6H5OH(X(1)A(')) + hv ->
      C6H5OH(A(1)A('), B(1)A('')) -> C6H5O(X(2)B1, A(2)B2) + H as a test case. Ab
      initio electronic structure data for the 1,2,3(1)A states of phenol, which are
      coupled by conical intersections, are obtained from multireference first order
      configuration interaction wave functions. The design of bases to simultaneously
      treat large amplitude motion and dissociation is described, as is the ability of
      the fitting procedure to smooth the irregularities in the electronic energies
      attributable to the orbital changes that are inherent to nonadiabatic processes.

PMID- 24437871
TI  - Prediction of (1)P Rydberg energy levels of beryllium based on calculations with
      explicitly correlated Gaussians.
AB  - Benchmark variational calculations are performed for the seven lowest 1s(2)2s np
      ((1)P), n = 2...8, states of the beryllium atom. The calculations explicitly
      include the effect of finite mass of (9)Be nucleus and account perturbatively for
      the mass-velocity, Darwin, and spin-spin relativistic corrections. The wave
      functions of the states are expanded in terms of all-electron explicitly
      correlated Gaussian functions. Basis sets of up to 12,500 optimized Gaussians are
      used. The maximum discrepancy between the calculated nonrelativistic and
      experimental energies of 1s(2)2s np ((1)P) ->1s(2)2s(2) ((1)S) transition is
      about 12 cm(-1). The inclusion of the relativistic corrections reduces the
      discrepancy to bellow 0.8 cm(-1).

PMID- 24437872
TI  - Photo-fragmentation spectroscopy of benzylium and 1-phenylethyl cations.
AB  - The electronic spectra of cold benzylium (C6H5-CH2 (+)) and 1-phenylethyl (C6H5
      CH-CH3 (+)) cations have been recorded via photofragment spectroscopy. Benzylium
      and 1-phenylethyl cations produced from electrosprayed benzylamine and
      phenylethylamine solutions, respectively, were stored in a cryogenically cooled
      quadrupole ion trap and photodissociated by an OPO laser, scanned in parts of the
      UV and visible regions (600-225 nm). The electronic states and active vibrational
      modes of the benzylium and 1-phenylethyl cations as well as those of their
      tropylium or methyl tropylium isomers have been calculated with ab initio methods
      for comparison with the spectra observed. Sharp vibrational progressions are
      observed in the visible region while the absorption features are much broader in
      the UV. The visible spectrum of the benzylium cation is similar to that obtained
      in an argon tagging experiment [V. Dryza, N. Chalyavi, J. A. Sanelli, and E. J.
      Bieske, J. Chem. Phys. 137, 204304 (2012)], with an additional splitting assigned
      to Fermi resonances. The visible spectrum of the 1-phenylethyl cation also shows
      vibrational progressions. For both cations, the second electronic transition is
      observed in the UV, around 33,000 cm(-1) (4.1 eV) and shows a broadened
      vibrational progression. In both cases the S2 optimized geometry is non-planar.
      The third electronic transition observed around 40,000 cm(-1) (5.0 eV) is even
      broader with no apparent vibrational structures, which is indicative of either a
      fast non-radiative process or a very large change in geometry between the excited
      and the ground states. The oscillator strengths calculated for tropylium and
      methyl tropylium are weak. Therefore, these isomeric structures are most likely
      not responsible for these absorption features. Finally, the fragmentation pattern
      changes in the second and third electronic states: C2H2 loss becomes predominant
      at higher excitation energies, for both cations.

PMID- 24437873
TI  - Electronic structure and reactivity in water splitting of the iron oxide dimers
      and their hexacarbonyls: a density functional study.
AB  - The iron oxide dimers (FeO)2 and their peroxide isomers are studied with the
      B3LYP density functional as bare clusters and as hexacarbonyls. Among the bare
      clusters the planar four-member ring structures are more stable than the non
      planar ones and the rhombic dioxide Fe2O2 with antiferromagnetically ordered
      electrons on iron centers is the global minimum. Water adsorption on the bare
      diiron dioxide is exothermic, but dissociation does not occur. Carbonylation
      favors a non-planar Fe2O2 ring for both the dioxides and the peroxides and high
      electron density at the Fe centers is induced, evidenced by the natural charge
      distribution, the high proton affinity, and the values of global
      electronegativity and hardness. The iron dioxide hexacarbonyl Fe2O2(CO)6 is
      diamagnetic in the state of the global minimum. It is separated from the next low
      lying triplet state by a small energy gap of 0.22 eV. Time-dependent density
      functional theory methods were applied to examine electron excitations from the
      ground state to the low-lying triplet states in the hexacarbonyls and their
      adsorption complexes with water. Singlet-to-triplet state excitations occur via
      ligand-to-metal charge transfer in the hexacarbonyls; in the adsorption complexes
      excitations from the oxygen lone pairs to the adsorption center also occur and
      they appear in the IR-visible region. The lowest energy singlet and triplet state
      reaction paths for water splitting were followed. On the singlet potential energy
      surface (PES), water splitting is spontaneous, while for the triplet PES an
      activation barrier of 14.1 kJ mol(-1) was determined. 

PMID- 24437874
TI  - A relativistic time-dependent density functional study of the excited states of
      the mercury dimer.
AB  - In previous works on Zn2 and Cd2 dimers we found that the long-range corrected
      CAMB3LYP gives better results than other density functional approximations for
      the excited states, especially in the asymptotic region. In this paper, we use it
      to present a time-dependent density functional (TDDFT) study for the ground-state
      as well as the excited states corresponding to the (6s(2) + 6s6p), (6s(2) +
      6s7s), and (6s(2) + 6s7p) atomic asymptotes for the mercury dimer Hg2. We analyze
      its spectrum obtained from all-electron calculations performed with the
      relativistic Dirac-Coulomb and relativistic spinfree Hamiltonian as implemented
      in DIRAC-PACKAGE. A comparison with the literature is given as far as available.
      Our result is excellent for the most of the lower excited states and very
      encouraging for the higher excited states, it shows generally good agreements
      with experimental results and outperforms other theoretical results. This enables
      us to give a detailed analysis of the spectrum of the Hg2 including a comparative
      analysis with the lighter dimers of the group 12, Cd2, and Zn2, especially for
      the relativistic effects, the spin-orbit interaction, and the performance of
      CAMB3LYP and is enlightened for similar systems. The result shows, as expected,
      that spinfree Hamiltonian is less efficient than Dirac-Coulomb Hamiltonian for
      systems containing heavy elements such as Hg2. 

PMID- 24437875
TI  - Parity violation in nuclear magnetic resonance frequencies of chiral tetrahedral
      tungsten complexes NWXYZ (X, Y, Z = H, F, Cl, Br or I).
AB  - Density functional theory within the two-component quasi-relativistic zeroth
      order regular approximation (ZORA) is used to predict parity violation shifts in
      (183)W nuclear magnetic resonance shielding tensors of chiral, tetrahedrally
      bonded tungsten complexes of the form NWXYZ (X, Y, Z = H, F, Cl, Br or I), as
      well as for the heavier systems NWHAtF and NWH(117)F for comparison. The
      calculations reveal that sub-mHz accuracy is required to detect such tiny effects
      in this class of compounds, and that parity violation effects are very sensitive
      to the choice of ligands. 

PMID- 24437876
TI  - Investigating the significance of zero-point motion in small molecular clusters
      of sulphuric acid and water.
AB  - The nucleation of particles from trace gases in the atmosphere is an important
      source of cloud condensation nuclei, and these are vital for the formation of
      clouds in view of the high supersaturations required for homogeneous water
      droplet nucleation. The methods of quantum chemistry have increasingly been
      employed to model nucleation due to their high accuracy and efficiency in
      calculating configurational energies; and nucleation rates can be obtained from
      the associated free energies of particle formation. However, even in such
      advanced approaches, it is typically assumed that the nuclei have a classical
      nature, which is questionable for some systems. The importance of zero-point
      motion (also known as quantum nuclear dynamics) in modelling small clusters of
      sulphuric acid and water is tested here using the path integral molecular
      dynamics method at the density functional level of theory. The general effect of
      zero-point motion is to distort the mean structure slightly, and to promote the
      extent of proton transfer with respect to classical behaviour. In a particular
      configuration of one sulphuric acid molecule with three waters, the range of
      positions explored by a proton between a sulphuric acid and a water molecule at
      300 K (a broad range in contrast to the confinement suggested by geometry
      optimisation at 0 K) is clearly affected by the inclusion of zero point motion,
      and similar effects are observed for other configurations. 

PMID- 24437877
TI  - The permanent electric dipole moment of thorium sulfide, ThS.
AB  - Numerous rotational lines of the {18.26}1-X(1)Sigma(+) band system of thorium
      sulfide, ThS, were recorded near 547.6 nm at a resolution of approximately 30
      MHz. Measurements were made under field-free conditions, and in the presence of a
      static electric field. The field-free spectrum was analyzed to produce rotational
      and Lambda-doubling parameters. The Stark shifts induced by the electric field
      were analyzed to determine permanent electric dipole moments, MU?el, of 4.58(10)
      D and 6.72(5) D for the X(1)Sigma(+) (v = 0) and {18.26}1 states, respectively.
      The results are compared with the predictions of previous and new electronic
      structure calculations for ThS, and the properties of isovalent ThO.

PMID- 24437878
TI  - Smallest fullerene-like silicon cage stabilized by a V(2) unit.
AB  - We conducted a combined anion photoelectron spectroscopy and density functional
      theory study on V2Si20 cluster. Our results show that the V2Si20 cluster has an
      elongated dodecahedron cage structure with a V2 unit encapsulated inside the
      cage. It is the smallest fullerene-like silicon cage and can be used as building
      block to make cluster-assembled materials, such as pearl-chain style nanowires. 

PMID- 24437879
TI  - An improved model electronic Hamiltonian for potential energy surfaces and spin
      orbit couplings of low-lying d-d states of [Fe(bpy)3]2+.
AB  - With the aim of exploring excited state dynamics, a model electronic Hamiltonian
      for several low-lying d-d states of [Fe(bpy)3](2+) complex [S. Iuchi, J. Chem.
      Phys. 136, 064519 (2012)] is refined using density-functional theory calculations
      of singlet, triplet, and quintet states as benchmarks. Spin-orbit coupling
      elements are also evaluated within the framework of the model Hamiltonian. The
      accuracy of the developed model Hamiltonian is determined by examining potential
      energies and spin-orbit couplings at surface crossing regions between different
      spin states. Insights into the potential energy surfaces around surface crossing
      regions are also provided through molecular dynamics simulations. The results
      demonstrate that the constructed model Hamiltonian can be used for studies on the
      d-d excited state dynamics of [Fe(bpy)3](2+). 

PMID- 24437880
TI  - Product fine-structure resolved photodissociation dynamics: the A band of H2O.
AB  - The photodissociation dynamics of H2O in its first absorption band is
      investigated on an accurate potential energy surface based on a large number of
      high-level ab initio points. Several ro-vibrational states of the parent molecule
      are considered. Different from most previous theoretical studies, the spin-orbit
      and Lambda-doublet populations of the open-shell OH fragment are reported from
      full-dimensional wave packet calculations. The populations of the two spin-orbit
      manifolds are in most cases close to the statistical limit, but the Lambda
      doublet is dominated by the A(") component, thanks largely to the fast in-plane
      dissociation of H2O(A(1)A('')). Comparisons with experimental data and a Franck
      Condon model are generally very good, although some discrepancies exist. 

PMID- 24437881
TI  - The effect of classical and quantum dynamics on vibrational frequency shifts of
      H2 in clathrate hydrates.
AB  - Vibrational frequency shifts of H2 in clathrate hydrates are important to
      understand the properties and elucidate details of the clathrate structure.
      Experimental spectra of H2 in clathrate hydrates have been measured for different
      clathrate compositions, temperatures, and pressures. In order to establish
      reliable relationships between the clathrate structure, dynamics, and observed
      frequencies, calculations of vibrational frequency shifts in different clathrate
      environments are required. In this study, a combination of classical molecular
      dynamics simulations, electronic structure calculations, and quantum dynamical
      simulation is used to calculate relative vibrational frequencies of H2 in
      clathrate hydrates. This approach allows us to assess dynamical effects and
      simulate the change of vibrational frequencies with temperature and pressure. The
      frequency distributions of the H2 vibrations in the different clathrate cage
      types agree favorably with experiment. Also, the simulations demonstrate that H2
      in the 5(12) cage is more sensitive to the details of the environment and to
      quantum dynamical effects, in particular when the cage is doubly occupied. We
      show that for the 5(12) cage quantum effects lead to frequency increases and
      double occupation is unlikely. This is different for the 5(12)6(4) cages for
      which higher occupation numbers than one H2 per cage are likely. 

PMID- 24437882
TI  - Reduced dimension rovibrational variational calculations of the S(1) state of
      C2H2. I. Methodology and implementation.
AB  - The bending and torsional degrees of freedom in S1 acetylene, C2H2, are subject
      to strong vibrational resonances and rovibrational interactions, which create
      complex vibrational polyad structures even at low energy. As the internal energy
      approaches that of the barrier to cis-trans isomerization, these energy level
      patterns undergo further large-scale reorganization that cannot be satisfactorily
      treated by traditional models tied to local minima of the potential energy
      surface for nuclear motion. Experimental spectra in the region near the cis-trans
      transition state have revealed these complicated new patterns. In order to
      understand near-barrier spectroscopic observations and to predict the detailed
      effects of cis-trans isomerization on the rovibrational energy level structure,
      we have performed reduced dimension rovibrational variational calculations of the
      S1 state. In this paper, we present the methodological details, several of which
      require special care. Our calculation uses a high accuracy ab initio potential
      surface and a fully symmetrized extended complete nuclear permutation inversion
      group theoretical treatment of a multivalued internal coordinate system that is
      appropriate for large amplitude bending and torsional motions. We also discuss
      the details of the rovibrational basis functions and their symmetrization, as
      well as the use of a constrained reduced dimension rovibrational kinetic energy
      operator. 

PMID- 24437883
TI  - Reduced dimension rovibrational variational calculations of the S(1) state of
      C2H2. II. The S(1) rovibrational manifold and the effects of isomerization.
AB  - Reduced dimension variational calculations have been performed for the
      rovibrational level structure of the S1 state of acetylene. The state exhibits an
      unusually complicated level structure, for various reasons. First, the potential
      energy surface has two accessible conformers, trans and cis. The cis conformer
      lies about 2700 cm(-1) above the trans, and the barrier to cis-trans
      isomerization lies about 5000 cm(-1) above the trans minimum. The trans
      vibrations nu4 (torsion) and nu6 (asym. bend) interact very strongly by Darling
      Dennison and Coriolis resonances, such that their combination levels and
      overtones form polyads with unexpected structures. Both conformers exhibit very
      large x36 cross-anharmonicity since the pathway to isomerization is a combination
      of nu6 and nu3 (sym. bend). Near the isomerization barrier, the vibrational
      levels show an even-odd K-staggering of their rotational levels as a result of
      quantum mechanical tunneling through the barrier. The present calculations
      address all of these complications, and reproduce the observed K-structures of
      the bending and C-C stretching levels with good qualitative accuracy. It is
      expected that they will assist with the assignment of the irregular patterns near
      the isomerization barrier. 

PMID- 24437884
TI  - Positive and negative ion formation in deep-core excited molecules: S 1s
      excitation in dimethyl sulfoxide.
AB  - The photo-fragmentation of the dimethyl sulfoxide (DMSO) molecule was studied
      using synchrotron radiation and a magnetic mass spectrometer. The total cationic
      yield spectrum was recorded in the photon energy region around the sulfur K edge.
      The sulfur composition of the highest occupied molecular orbital's and lowest
      unoccupied molecular orbital's in the DMSO molecule has been obtained using both
      ab initio and density functional theory methods. Partial cation and anion-yield
      measurements were obtained in the same energy range. An intense resonance is
      observed at 2475.4 eV. Sulfur atomic ions present a richer structure around this
      resonant feature, as compared to other fragment ions. The yield curves are
      similar for most of the other ionic species, which we interpret as due to cascade
      Auger processes leading to multiply charged species which then undergo Coulomb
      explosion. The anions S(-), C(-), and O(-) are observed for the first time in
      deep-core-level excitation of DMSO. 

PMID- 24437885
TI  - Protonation effect on the electronic properties of 2-pyridone monomer, dimer and
      its water clusters: a theoretical study.
AB  - The CC2 (second order approximate coupled cluster method) has been applied to
      investigate protonation effect on electronic transition energies of 2-pyridone
      (2PY), 2-pyridone dimer, and micro-solvated 2-pyridone (0-2 water molecules). The
      PE profiles of protonated 2-pyridone (2PYH(+)) as well as monohydrated 2PYH(+) at
      the different electronic states have been investigated. The (1)pisigma* state in
      protonated species (2PYH(+)) is a barrier free and dissociative state along the O
      H stretching coordinate. In this reaction coordinate, the lowest lying
      (1)pisigma* predissociates the bound S1((1)pipi*) state, connecting the latter to
      a conical intersection with the S0 state. These conical intersections lead the
      (1)pipi* state to proceed as predissociative state and finally direct the excited
      system to the ground state. Furthermore, in presence of water molecule, the
      (1)pisigma* state still remains dissociative but the conical intersection between
      (1)pisigma* and ground state disappears. In addition, according to the CC2
      calculation results, it has been predicted that protonation significantly blue
      shifts the S1-S0 electronic transition of monomer, dimer, and microhydrated 2
      pyridone. 

PMID- 24437886
TI  - Time- and frequency-dependent model of time-resolved coherent anti-Stokes Raman
      scattering (CARS) with a picosecond-duration probe pulse.
AB  - The hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps
      CARS) technique presents a promising alternative to either fs time-resolved or ps
      frequency-resolved CARS in both gas-phase thermometry and condensed-phase excited
      state dynamics applications. A theoretical description of time-dependent CARS is
      used to examine this recently developed probe technique, and quantitative
      comparisons of the full time-frequency evolution show excellent accuracy in
      predicting the experimental vibrational CARS spectra obtained for two model
      systems. The interrelated time- and frequency-domain spectral signatures of gas
      phase species produced by hybrid fs/ps CARS are explored with a focus on gas
      phase N2 vibrational CARS, which is commonly used as a thermometric diagnostic of
      combusting flows. In particular, we discuss the merits of the simple top-hat
      spectral filter typically used to generate the ps-duration hybrid fs/ps CARS
      probe pulse, including strong discrimination against non-resonant background that
      often contaminates CARS signal. It is further demonstrated, via comparison with
      vibrational CARS results on a time-evolving solvated organic chromophore, that
      this top-hat probe-pulse configuration can provide improved spectral resolution,
      although the degree of improvement depends on the dephasing timescales of the
      observed molecular modes and the duration and timing of the narrowband final
      pulse. Additionally, we discuss the virtues of a frequency-domain Lorentzian
      probe-pulse lineshape and its potential for improving the hybrid fs/ps CARS
      technique as a diagnostic in high-pressure gas-phase thermometry applications. 

PMID- 24437887
TI  - Shape resonance spectra of uracil, 5-fluorouracil, and 5-chlorouracil.
AB  - We report on the shape resonance spectra of uracil, 5-fluorouracil, and 5
      chlorouracil, as obtained from fixed-nuclei elastic scattering calculations
      performed with the Schwinger multichannel method with pseudopotentials. Our
      results are in good agreement with the available electron transmission
      spectroscopy data, and support the existence of three pi* resonances in uracil
      and 5-fluorouracil. As expected, the anion states are more stable in the
      substituted molecules than in uracil. Since the stabilization is stronger in 5
      chlorouracil, the lowest pi* resonance in this system becomes a bound anion
      state. The present results also support the existence of a low-lying sigmaCCl (*)
      shape resonance in 5-chlorouracil. Exploratory calculations performed at selected
      C-Cl bond lengths suggest that the sigmaCCl (*) resonance could couple to the two
      lowest pi* states, giving rise to a very rich dissociation dynamics. These facts
      would be compatible with the complex branching of the dissociative electron
      attachment cross sections, even though we cannot discuss any details of the
      vibration dynamics based only on the present fixed-nuclei results. 

PMID- 24437888
TI  - Wave function for harmonically confined electrons in time-dependent electric and
      magnetostatic fields.
AB  - We derive via the interaction "representation" the many-body wave function for
      harmonically confined electrons in the presence of a magnetostatic field and
      perturbed by a spatially homogeneous time-dependent electric field-the
      Generalized Kohn Theorem (GKT) wave function. In the absence of the harmonic
      confinement - the uniform electron gas - the GKT wave function reduces to the
      Kohn Theorem wave function. Without the magnetostatic field, the GKT wave
      function is the Harmonic Potential Theorem wave function. We further prove the
      validity of the connection between the GKT wave function derived and the system
      in an accelerated frame of reference. Finally, we provide examples of the
      application of the GKT wave function. 

PMID- 24437889
TI  - The influence of a presence of a heavy atom on the spin-spin coupling constants
      between two light nuclei in organometallic compounds and halogen derivatives.
AB  - The (1)JCC and (1)JCH spin-spin coupling constants have been calculated by means
      of density functional theory (DFT) for a set of derivatives of aliphatic
      hydrocarbons substituted with I, At, Cd, and Hg in order to evaluate the
      substituent and relativistic effects for these properties. The main goal was to
      estimate HALA (heavy-atom-on-light-atom) effects on spin-spin coupling constants
      and to explore the factors which may influence the HALA effect on these
      properties, including the nature of the heavy atom substituent and carbon
      hybridization. The methods applied range, in order of reduced complexity, from
      Dirac-Kohn-Sham method (density functional theory with four-component Dirac
      Coulomb Hamiltonian), through DFT with two- and one-component Zeroth Order
      Regular Approximation (ZORA) Hamiltonians, to scalar non-relativistic effective
      core potentials with the non-relativistic Hamiltonian. Thus, we are able to
      compare the performance of ZORA-DFT and Dirac-Kohn-Sham methods for modelling of
      the HALA effects on the spin-spin coupling constants. 

PMID- 24437890
TI  - Turing-Hopf instabilities through a combination of diffusion, advection, and
      finite size effects.
AB  - We show that in a reaction diffusion system on a two-dimensional substrate with
      advection in the confined direction, the drift (advection) induced instability
      occurs through a Hopf bifurcation, which can become a double Hopf bifurcation.
      The box size in the direction of the drift is a vital parameter. Our analysis
      involves reduction to a low dimensional dynamical system and constructing
      amplitude equations. 

PMID- 24437891
TI  - The application of the integral equation theory to study the hydrophobic
      interaction.
AB  - The Wertheim's integral equation theory was tested against newly obtained Monte
      Carlo computer simulations to describe the potential of mean force between two
      hydrophobic particles. An excellent agreement was obtained between the
      theoretical and simulation results. Further, the Wertheim's integral equation
      theory with polymer Percus-Yevick closure qualitatively correctly (with respect
      to the experimental data) describes the solvation structure under conditions
      where the simulation results are difficult to obtain with good enough accuracy. 

PMID- 24437892
TI  - Anisotropy of singlet exciton diffusion in organic semiconductor crystals from ab
      initio approaches.
AB  - Due to its importance for the function of organic optoelectronic devices,
      accurate simulations of the singlet exciton diffusion are crucial to predict the
      performance of new materials. We present a protocol which allows for the
      efficient directional analysis of exciton transport with high-level ab initio
      methods. It is based on an alternative to the frequently employed rate equation
      since the latter was found to be erroneous in some cases. The new approach can be
      used in combination with the master equation which is considerably faster than
      the corresponding Monte Carlo approach. The long-range character of the singlet
      exciton coupling is taken into account by an extrapolation scheme. The approach
      is applied to singlet exciton diffusion in those substances where these
      quantities are experimentally best established: naphthalene and anthracene. The
      high quality of the crystals, furthermore, diminish uncertainties arising from
      the geometrical structures used in the computations. For those systems, our new
      approach provides exciton diffusion lengths L for naphthalene and anthracene
      crystals which show an excellent agreement with their experimental counterparts.
      For anthracene, for example, the computed L value in a direction is computed to
      58 nm while the experimental value is 60 +/- 10 nm. 

PMID- 24437893
TI  - Reverse Monte Carlo modeling in confined systems.
AB  - An extension of the well established Reverse Monte Carlo (RMC) method for
      modeling systems under close confinement has been developed. The method overcomes
      limitations induced by close confinement in systems such as fluids adsorbed in
      microporous materials. As a test of the method, we investigate a model system of
      (36)Ar adsorbed into two zeolites with significantly different pore sizes:
      Silicalite-I (a pure silica form of ZSM-5 zeolite, characterized by relatively
      narrow channels forming a 3D network) at partial and full loadings and siliceous
      Faujasite (which exhibits relatively wide channels and large cavities). The model
      systems are simulated using grand canonical Monte Carlo and, in each case, its
      structure factor is used as input for the proposed method, which shows a rapid
      convergence and yields an adsorbate microscopic structure in good agreement with
      that of the model system, even to the level of three body correlations, when
      these are induced by the confining media. The application to experimental systems
      is straightforward incorporating factors such as the experimental resolution and
      appropriate q-sampling, along the lines of previous experiences of RMC modeling
      of powder diffraction data including Bragg and diffuse scattering. 

PMID- 24437894
TI  - A transition state theory for calculating hopping times and diffusion in highly
      confined fluids.
AB  - Monte Carlo simulation is used to study the dynamical crossover from single file
      diffusion to normal diffusion in fluids confined to narrow channels. We show that
      the long time diffusion coefficients for a series of systems involving hard and
      soft interaction potentials can be described in terms of a hopping time that
      measures the time it takes for a particle to escape the cage formed by its
      neighbors in the pore. Free energy barriers for the particle hopping process are
      calculated and used to show that transition state theory effectively describes
      the hopping time for all the systems studied over a range of pore radii. Our work
      suggests that the combination of hopping times and transition state theory offers
      a useful and general framework to describe the dynamics of highly confined,
      single file fluids. 

PMID- 24437895
TI  - Continuous distributions of charges: extensions of the one component plasma.
AB  - The electrostatic interaction between finite charge distributions, rho(r), in a
      neutralizing background is considered as an extension of the one component plasma
      (OCP) model of point charges. A general form for the interaction potential is
      obtained which can be applied to molecular theories of many simple charged fluids
      and mixtures and to the molecular dynamics (MD) simulation of such systems. The
      formalism is applied to the study of a fluid of Gaussian charges in a
      neutralizing background by MD simulation and using hypernetted-chain integral
      equation theory. The treatment of these interactions is extended to a periodic
      system using a Fourier Transform formulation and, for a rapidly decaying charge
      distribution, an application of the Ewald method. The contributions of the self
      energy and neutralizing background to the system's energy are explicitly included
      in the formulation. Calculations reveal differences in behavior from the OCP
      model when the Wigner-Seitz radius is of order and less than the Gaussian charge
      density decay length. For certain parameter values these systems can exhibit a
      multiple occupancy crystalline phase at high density which undergoes re-entrant
      melting at higher density. An exploration of the effects of the various length
      scales of the system on the equation of state and radial distribution function is
      made. 

PMID- 24437896
TI  - Electronic structure changes during the surface-assisted formation of a graphene
      nanoribbon.
AB  - High conductivity and a tunability of the band gap make quasi-one-dimensional
      graphene nanoribbons (GNRs) highly interesting materials for the use in field
      effect transistors. Especially bottom-up fabricated GNRs possess well-defined
      edges which is important for the electronic structure and accordingly the band
      gap. In this study we investigate the formation of a sub-nanometer wide armchair
      GNR generated on a Au(111) surface. The on-surface synthesis is thermally
      activated and involves an intermediate non-aromatic polymer in which the
      molecular precursor forms polyanthrylene chains. Employing angle-resolved two
      photon photoemission in combination with density functional theory calculations
      we find that the polymer exhibits two dispersing states which we attribute to the
      valence and the conduction band, respectively. While the band gap of the non
      aromatic polymer obtained in this way is relatively large, namely 5.25 +/- 0.06
      eV, the gap of the corresponding aromatic GNR is strongly reduced which we
      attribute to the different degree of electron delocalization in the two systems. 

PMID- 24437897
TI  - Finite-temperature second-order many-body perturbation and Hartree-Fock theories
      for one-dimensional solids: an application to Peierls and charge-density-wave
      transitions in conjugated polymers.
AB  - Finite-temperature extensions of ab initio Gaussian-basis-set spin-restricted
      Hartree-Fock (HF) and second-order many-body perturbation (MP2) theories are
      implemented for infinitely extended, periodic, one-dimensional solids and applied
      to the Peierls and charge-density-wave (CDW) transitions in polyyne and all-trans
      polyacetylene. The HF theory predicts insulating CDW ground states for both
      systems in their equidistant structures at low temperatures. In the same
      structures, they turn metallic at high temperatures. Starting from the
      "dimerized" low-temperature equilibrium structures, the systems need even higher
      temperatures to undergo a Peierls transition, which is accompanied by geometric
      as well as electronic distortions from dimerized to non-dimerized forms. The
      conventional finite-temperature MP2 theory shows a sign of divergence in any
      phase at any nonzero temperature and is useless. The renormalized finite
      temperature MP2 (MP2R) theory is divergent only near metallic electronic
      structures, but is well behaved elsewhere. MP2R also predicts CDW and Peierls
      transitions occurring at two different temperatures. The effect of electron
      correlation is primarily to lower the Peierls transition temperature. 

PMID- 24437898
TI  - Calculation of the interfacial free energy of a binary hard-sphere fluid at a
      planar hard wall.
AB  - Using molecular-dynamics simulation and Gibbs-Cahn Integration, we calculate the
      interfacial free energy gamma of a binary hard-sphere fluid mixture at a
      structureless, planar hard wall. The calculation is performed as a function of
      packing fraction (density) for several values of the diameter ratio alpha =
      sigma2/sigma1, where sigma1 and sigma2 are the diameters of the two particle
      types in the mixture. Our results are compared to those obtained from the bulk
      version of the White Bear Mark II (WBII) classical density-functional theory,
      which is a modification of the Fundamental-Measure Theory of Rosenfeld. The WBII
      bulk theory is shown to be in very good agreement with the simulation results,
      with significant deviation only at the very highest packing fractions. 

PMID- 24437899
TI  - Thermodynamic stability of nanosized multicomponent bubbles/droplets: the square
      gradient theory and the capillary approach.
AB  - Formation of nanosized droplets/bubbles from a metastable bulk phase is connected
      to many unresolved scientific questions. We analyze the properties and stability
      of multicomponent droplets and bubbles in the canonical ensemble, and compare
      with single-component systems. The bubbles/droplets are described on the
      mesoscopic level by square gradient theory. Furthermore, we compare the results
      to a capillary model which gives a macroscopic description. Remarkably, the
      solutions of the square gradient model, representing bubbles and droplets, are
      accurately reproduced by the capillary model except in the vicinity of the
      spinodals. The solutions of the square gradient model form closed loops, which
      shows the inherent symmetry and connected nature of bubbles and droplets. A
      thermodynamic stability analysis is carried out, where the second variation of
      the square gradient description is compared to the eigenvalues of the Hessian
      matrix in the capillary description. The analysis shows that it is impossible to
      stabilize arbitrarily small bubbles or droplets in closed systems and gives
      insight into metastable regions close to the minimum bubble/droplet radii.
      Despite the large difference in complexity, the square gradient and the capillary
      model predict the same finite threshold sizes and very similar stability limits
      for bubbles and droplets, both for single-component and two-component systems. 

PMID- 24437900
TI  - Solid phases of spatially nanoconfined oxygen: a neutron scattering study.
AB  - We present a comprehensive neutron scattering study on solid oxygen spatially
      confined in 12 nm wide alumina nanochannels. Elastic scattering experiments
      reveal a structural phase sequence known from bulk oxygen. With decreasing
      temperature cubic gamma-, orthorhombic beta- and monoclinic alpha-phases are
      unambiguously identified in confinement. Weak antiferromagnetic ordering is
      observed in the confined monoclinic alpha-phase. Rocking scans reveal that oxygen
      nanocrystals inside the tubular channels do not form an isotropic powder. Rather,
      they exhibit preferred orientations depending on thermal history and the very
      mechanisms, which guide the structural transitions. 

PMID- 24437901
TI  - Temperature effects on adsorption and diffusion dynamics of CH3CH2(ads) and H3C
      C=C(ads) on Ag(111) surface and their self-coupling reactions: ab initio
      molecular dynamics approach.
AB  - Density functional theory (DFT)-based molecular dynamics (DFTMD) simulations in
      combination with a Fourier transform of dipole moment autocorrelation function
      are performed to investigate the adsorption dynamics and the reaction mechanisms
      of self-coupling reactions of both acetylide (H3C-C(beta)=C(alpha) (ads)) and
      ethyl (H3C(beta)-C(alpha)H2(ads)) with I(ads) coadsorbed on the Ag(111) surface
      at various temperatures. In addition, the calculated infrared spectra of H3C
      C(beta)=C(alpha)(ads) and I coadsorbed on the Ag(111) surface indicate that the
      active peaks of -C(beta)=C(alpha)- stretching are gradually merged into one peak
      as a result of the dominant motion of the stand-up -C-C(beta)=C(alpha)- axis as
      the temperature increases from 200 K to 400 K. However, the calculated infrared
      spectra of H3C(beta)-C(alpha)H2(ads) and I coadsorbed on the Ag(111) surface
      indicate that all the active peaks are not altered as the temperature increases
      from 100 K to 150 K because only one orientation of H3C(beta)-C(alpha)H2(ads)
      adsorbed on the Ag(111) surface has been observed. These calculated IR spectra
      are in a good agreement with experimental reflection absorption infrared
      spectroscopy results. Furthermore, the dynamics behaviors of H3C
      C(beta)=C(alpha)(ads) and I coadsorbed on the Ag(111) surface point out the less
      diffusive ability of H3C-C(beta)=C(alpha)(ads) due to the increasing s-character
      of Calpha leading to the stronger Ag-Calpha bond in comparison with that of
      H3C(beta)-C(alpha)H2(ads) and I coadsorbed on the same surface. Finally, these
      DFTMD simulation results allow us to predict the energetically more favourable
      reaction pathways for self-coupling of both H3C-C(beta)=C(alpha)(ads) and
      H3C(beta)-C(alpha)H2(ads) adsorbed on the Ag(111) surface to form 2,4-hexadiyne
      (H3C-C=C-C=C-CH3(g)) and butane (CH3-CH2-CH2-CH3(g)), respectively. The
      calculated reaction energy barriers for both H3C-C=C-C=C-CH3(g) (1.34 eV) and CH3
      CH2-CH2-CH3(g) (0.60 eV) are further employed with the Redhead analysis to
      estimate the desorption temperatures approximately at 510 K and 230 K,
      respectively, which are in a good agreement with the experimental low-coverage
      temperature programmed reaction spectroscopy measurements. 

PMID- 24437902
TI  - Nitrogen-induced reconstruction and faceting of Re(1121).
AB  - The surface morphology of Re(1121), tailored on the nanometer scale by kinetic
      control of nitrogen, has been investigated using low energy electron diffraction,
      scanning tunneling microscopy, Auger electron spectroscopy, and density
      functional theory (DFT) in combination with the ab initio atomistic
      thermodynamics approach. Experiments show that when exposing to NH3 (>0.5 L) at
      300 K followed by annealing in ultra-high vacuum at 700 K or 900 K, the initially
      planar Re(1121) surface becomes (2 * 1) reconstructed or partially faceted,
      respectively. Upon annealing in 100 L NH3 at 900 K, Re(1121) becomes fully
      faceted and covered by N. The fully faceted surface consists of two-sided ridges
      formed by (1342) and (3142) facets. The (2 * 1) reconstruction may serve as a
      precursor state for faceting of Re(1121). The DFT calculations provide an
      atomistic understanding of facet formation in terms of binding sites and energies
      of N on Re surfaces of the substrate and facets as well as the corresponding
      surface phase diagram. The N-covered faceted Re(1121) surfaces are promising
      nanoscale model catalysts and nanotemplates. Our findings should be of importance
      for the design and development of Re-based heterogeneous catalysts operating
      under nitrogen-rich conditions.

PMID- 24437903
TI  - A kinetic model for heterogeneous condensation of vapor on an insoluble spherical
      particle.
AB  - A kinetic model is developed to describe the heterogeneous condensation of vapor
      on an insoluble spherical particle. This new model considers two mechanisms of
      cluster growth: direct addition of water molecules from the vapor and surface
      diffusion of adsorbed water molecules on the particle. The effect of line tension
      is also included in the model. For the first time, the exact expression of
      evaporation coefficient is derived for heterogeneous condensation of vapor on an
      insoluble spherical particle by using the detailed balance. The obtained
      expression of evaporation coefficient is proved to be also correct in the
      homogeneous condensation and the heterogeneous condensation on a planar solid
      surface. The contributions of the two mechanisms to heterogeneous condensation
      including the effect of line tension are evaluated and analysed. It is found that
      the cluster growth via surface diffusion of adsorbed water molecules on the
      particle is more important than the direct addition from the vapor. As an example
      of our model applications, the growth rate of the cap shaped droplet on the
      insoluble spherical particle is derived. Our evaluation shows that the growth
      rate of droplet in heterogeneous condensation is larger than that in homogeneous
      condensation. These results indicate that an explicit kinetic model is benefit to
      the study of heterogeneous condensation on an insoluble spherical particle. 

PMID- 24437904
TI  - Second order classical perturbation theory for atom surface scattering: analysis
      of asymmetry in the angular distribution.
AB  - A second order classical perturbation theory is developed and applied to elastic
      atom corrugated surface scattering. The resulting theory accounts for
      experimentally observed asymmetry in the final angular distributions. These
      include qualitative features, such as reduction of the asymmetry in the intensity
      of the rainbow peaks with increased incidence energy as well as the asymmetry in
      the location of the rainbow peaks with respect to the specular scattering angle.
      The theory is especially applicable to "soft" corrugated potentials. Expressions
      for the angular distribution are derived for the exponential repulsive and Morse
      potential models. The theory is implemented numerically to a simplified model of
      the scattering of an Ar atom from a LiF(100) surface. 

PMID- 24437905
TI  - Generalized Onsager theory for strongly anisometric patchy colloids.
AB  - The implications of soft "patchy" interactions on the orientational disorder
      order transition of strongly elongated colloidal rods and flat disks is studied
      within a simple Onsager-van der Waals density functional theory. The theory
      provides a generic framework for studying the liquid crystal phase behaviour of
      highly anisometric cylindrical colloids which carry a distinct geometrical
      pattern of repulsive or attractive soft interactions localized on the particle
      surface. In this paper, we apply our theory to the case of charged rods and disks
      for which the local electrostatic interactions can be described by a screened
      Coulomb potential. We consider infinitely thin rod like cylinders with a uniform
      line charge and infinitely thin discotic cylinders with several distinctly
      different surface charge patterns. Irrespective of the backbone shape the
      isotropic-nematic phase diagrams of charged colloids feature a generic
      destabilization of nematic order at low ionic strength, a dramatic narrowing of
      the biphasic density region, and a reentrant phenomenon upon reducing the
      electrostatic screening. The low screening regime is characterized by a complete
      suppression of nematic order in favor of positionally ordered liquid crystal
      phases. 

PMID- 24437906
TI  - Molecular dynamics simulations of shock waves in hydroxyl-terminated
      polybutadiene melts: mechanical and structural responses.
AB  - The mechanical and structural responses of hydroxyl-terminated cis-1,4
      polybutadiene melts to shock waves were investigated by means of all-atom non
      reactive molecular dynamics simulations. The simulations were performed using the
      OPLS-AA force field but with the standard 12-6 Lennard-Jones potential replaced
      by the Buckingham exponential-6 potential to better represent the interactions at
      high compression. Monodisperse systems containing 64, 128, and 256 backbone
      carbon atoms were studied. Supported shock waves were generated by impacting the
      samples onto stationary pistons at impact velocities of 1.0, 1.5, 2.0, and 2.5 km
      s(-1), yielding shock pressures between approximately 2.8 GPa and 12.5 GPa.
      Single-molecule structural properties (squared radii of gyration, asphericity
      parameters, and orientational order parameters) and mechanical properties
      (density, shock pressure, shock temperature, and shear stress) were analyzed
      using a geometric binning scheme to obtain spatio-temporal resolution in the
      reference frame centered on the shock front. Our results indicate that while
      shear stress behind the shock front is relieved on a ~0.5 ps time scale, a shock
      induced transition to a glass-like state occurs with a concomitant increase of
      structural relaxation times by several orders of magnitude. 

PMID- 24437907
TI  - Shape variation of micelles in polymer thin films.
AB  - The equilibrium properties of block copolymer micelles confined in polymer thin
      films are investigated using self-consistent field theory. The theory is based on
      a model system consisting of AB diblock copolymers and A homopolymers. Two
      different methods, based on the radius of gyration tensor and the spherical
      harmonics expansion, are used to characterize the micellar shape. The results
      reveal that the morphology of micelles in thin films depends on the thickness of
      the thin films and the selectivity of the confining surfaces. For spherical
      (cylindrical) micelles, the spherical (cylindrical) symmetry is broken by the
      presence of the one-dimensional confinement, whereas the top-down symmetry is
      broken by the selectivity of the confining surfaces. Morphological transitions
      from spherical or cylindrical micelles to cylinders or lamella are predicted when
      the film thickness approaches the micellar size. 

PMID- 24437908
TI  - Organization of polymer chains onto long, single-wall carbon nano-tubes: effect
      of tube diameter and cooling method.
AB  - We use molecular dynamics simulations to investigate the arrangement of polymer
      chains when absorbed onto a long, single-wall carbon nano-tube (SWCNT). We study
      the conformation and organization of the polymer chains on the SWCNT and their
      dependence on the tube's diameter and the rate of cooling. We use two types of
      cooling processes: direct quenching and gradual cooling. The radial density
      distribution function and bond orientational order parameter are used to
      characterize the polymer chain structure near the surface. In the direct cooling
      process, the beads of the polymer chain organize in lamella-like patterns on the
      surface of the SWCNT with the long axis of the lamella parallel to the axis of
      the SWCNT. In a stepwise, gradual cooling process, the polymer beads form a
      helical pattern on the surface of a relatively thick SWCNT, but form a lamella
      like pattern on the surface of a very thin SWCNT. We develop a theoretical (free
      energy) model to explain this difference in pattern structures for the gradual
      cooling process and also provide a qualitative explanation for the pattern that
      forms from the direct cooling process. 

PMID- 24437909
TI  - Coherent states formulation of polymer field theory.
AB  - We introduce a stable and efficient complex Langevin (CL) scheme to enable the
      first direct numerical simulations of the coherent-states (CS) formulation of
      polymer field theory. In contrast with Edwards' well-known auxiliary-field (AF)
      framework, the CS formulation does not contain an embedded nonlinear, non-local,
      implicit functional of the auxiliary fields, and the action of the field theory
      has a fully explicit, semi-local, and finite-order polynomial character. In the
      context of a polymer solution model, we demonstrate that the new CS-CL dynamical
      scheme for sampling fluctuations in the space of coherent states yields results
      in good agreement with now-standard AF-CL simulations. The formalism is
      potentially applicable to a broad range of polymer architectures and may
      facilitate systematic generation of trial actions for use in coarse-graining and
      numerical renormalization-group studies. 

PMID- 24437910
TI  - Effects of ionic liquids on cation dynamics in amorphous polyethylene oxide
      electrolytes.
AB  - We perform extensive molecular dynamics simulations of a poly(ethylene oxide)
      based polymer electrolyte material containing lithium
      bis(trifluoromethanesulfonyl)imide salt for a wide temperature regime above and
      below the experimental crystallization temperature with and without N-methyl-N
      propylpyrrolidinium bis(trifluoromethanesulfonyl)imide ionic liquid (IL). The
      impact of the IL-concentration on the cation dynamics is studied. The increase of
      the cation mobility upon addition of IL is significant but temperature
      independent. This can be related to distinct variations of the underlying
      transport properties as expressed within the previously introduced transport
      model of polymer electrolytes. Even for the largest IL concentration the
      transport model perfectly predicts the non-trivial time-dependence of the
      cationic mean square displacement for all temperatures. Finally, we compare our
      numerical and theoretical findings with the results of recent nuclear magnetic
      resonance experiments. In this way we can exclusively relate the strong
      experimentally observed dependence of the low-temperature Li-diffusivity on the
      IL concentration to the impact of IL on crystallization. 

PMID- 24437911
TI  - Rigidity of a spherical capsule switches the localization of encapsulated
      particles between inner and peripheral regions under crowding condition: simple
      model on cellular architecture.
AB  - We have investigated the inhomogeneous interior of confined spherical cavities as
      capsules containing encapsulated binary hard sphere mixtures for different
      compositions and cavity wall rigidity. Such a greatly simplified model manifests
      the effects of macromolecular crowding arising from excluded volume interactions
      in a tiny cell or a cellular nucleus. By fixing the number of large particles,
      the level of crowding is adjusted by changing the amount of small hard spheres in
      the cavity. For a rigid cavity, large spheres tend to pack in liquid-like order
      apart from the surface to the center of the cavity as the crowding level is
      increased. Whereas, for a soft cavity, larger spheres tend to blend with small
      spheres in the peripheral region at near the boundary of the cavity, and are
      susceptible to be depleted from the interior of the cavity as the cavity becomes
      more crowded. These results may help future elucidation of the thermodynamic
      pathways to stabilize the inhomogeneous structure of mixtures confined in
      cavities, such as the derepression of genome materials around the interior rim of
      the nucleus in a cancerous cell. 

PMID- 24437912
TI  - Revisit to phase diagram of poly(N-isopropylacrylamide) microgel suspensions by
      mechanical spectroscopy.
AB  - Microgels are soft particles that can be deformed and compressed, which would
      induce intriguing phase behaviors at high packing fractions. Poly(N
      isopropylacrylamide) (PNIPAM) microgels, with a lower critical solution
      temperature (LCST) of 33  degrees C, have attracted considerable interests as
      model colloids, since the volume of them and the interaction between the
      microgels can be tuned precisely by temperature. In this work, the linear
      viscoelastic properties of PNIPAM microgel suspensions have been investigated
      using mechanical spectroscopy. A particular attention is focused on the phase
      behaviors at high concentrations. With increasing concentration the system
      undergoes a repulsive glass-to-gel transition below the LCST, while, as
      temperature is raised across the LCST, the system undergoes a gel-to-attractive
      glass transition. A mechanism of these transitions for the microgels is proposed
      based on the directional interaction between the particles. In moderate
      concentration or de-swelling microgels the interaction is isotropic leading to
      the glass phase, while in concentrated and deformed microgels the interaction is
      directional leading to the gel phase. Our results enrich the current
      understanding of the phase transition in microgel systems and shed new light on
      the phase diagram of colloidal suspensions in general. 

PMID- 24437913
TI  - Slow dynamics of nanocomposite polymer aerogels as revealed by X-ray
      photocorrelation spectroscopy (XPCS).
AB  - We report on a novel slow dynamics of polymer xerogels, aerogels, and
      nanocomposite aerogels with iron oxide nanoparticles, as revealed by X-ray photon
      correlation spectroscopy. The polymer aerogel and its nanocomposite aerogels,
      which are porous in nature, exhibit hyper-diffusive dynamics at room temperature.
      In contrast, non-porous polymer xerogels exhibit an absence of this peculiar
      dynamics. This slow dynamical process has been assigned to a relaxation of the
      characteristic porous structure of these materials and not to the presence of
      nanoparticles. 

PMID- 24437914
TI  - Born energy, acid-base equilibrium, structure and interactions of end-grafted
      weak polyelectrolyte layers.
AB  - This work addresses the effect of the Born self-energy contribution in the
      modeling of the structural and thermodynamical properties of weak
      polyelectrolytes confined to planar and curved surfaces. The theoretical
      framework is based on a theory that explicitly includes the conformations, size,
      shape, and charge distribution of all molecular species and considers the acid
      base equilibrium of the weak polyelectrolyte. Namely, the degree of charge in the
      polymers is not imposed but it is a local varying property that results from the
      minimization of the total free energy. Inclusion of the dielectric properties of
      the polyelectrolyte is important as the environment of a polymer layer is very
      different from that in the adjacent aqueous solution. The main effect of the Born
      energy contribution on the molecular organization of an end-grafted weak polyacid
      layer is uncharging the weak acid (or basic) groups and consequently decreasing
      the concentration of mobile ions within the layer. The magnitude of the effect
      increases with polymer density and, in the case of the average degree of charge,
      it is qualitatively equivalent to a small shift in the equilibrium constant for
      the acid-base equilibrium of the weak polyelectrolyte monomers. The degree of
      charge is established by the competition between electrostatic interactions, the
      polymer conformational entropy, the excluded volume interactions, the
      translational entropy of the counterions and the acid-base chemical equilibrium.
      Consideration of the Born energy introduces an additional energetic penalty to
      the presence of charged groups in the polyelectrolyte layer, whose effect is
      mitigated by down-regulating the amount of charge, i.e., by shifting the local
      acid base equilibrium towards its uncharged state. Shifting of the local acid
      base equilibrium and its effect on the properties of the polyelectrolyte layer,
      without considering the Born energy, have been theoretically predicted
      previously. Account of the Born energy leads to systematic, but in general small,
      corrections to earlier theoretical predictions describing the behavior of weak
      polyelectrolyte layers. However, polyelectrolyte uncharging results in a decrease
      in the concentration of counterions and inclusion of the Born Energy can result
      in a substantial decrease of the counterion concentration. The effect of
      considering the Born energy contribution is explored for end-grafted weak
      polyelectrolyte layers by calculating experimental observables which are known to
      depend on the presence of charges within the polyelectrolyte layer: inclusion of
      the Born energy contribution leads to a decrease in the capacitance of
      polyelectrolyte-modified electrodes, a decrease of conductivity of
      polyelectrolyte-modified nanopores and an increase in the repulsion exerted by a
      planar polyelectrolyte layer confined by an opposing wall. 

PMID- 24437915
TI  - Study of the B1-B2 transition in colloidal clusters.
AB  - The possible mechanisms for the B1 (NaCl-type) to B2 (CsCl-type) transition in
      crystalline colloidal clusters of equally sized particles are studied by means of
      two computational techniques: metadynamics and nudged elastic band calculations.
      The system is modelled by a screened Coulomb potential. Different interaction
      ranges are considered. The transition from a perfect NaCl cubic cluster to a full
      CsCl cluster is forced by metadynamics, revealing a transition path with
      intermediate metastable configurations in which planes are shifted one by one.
      The presence of metastable configurations in the transition path, corresponding
      to a certain number of NaCl planes turned into CsCl, has clear analogies with the
      known Hyde and O'Keeffe mechanism for ionic crystals, with some important
      differences due to finite-size effects. These comprise the fact that the
      transition starts by shifting a surface plane by means of a row-by-row mechanism
      that has no analog in bulk crystals. The energy barriers between the local minima
      in the transition path are calculated, showing that the barriers strongly depend
      on the screening length, in such a way that the B1 metastable phase can have very
      long lifetimes when the interaction is sufficiently long-ranged. 

PMID- 24437916
TI  - Entropic force on granular chains self-extracting from one-dimensional
      confinement.
AB  - The entropic forces on the self-retracting granular chains, which are confined in
      channels with different widths, are determined. The time dependence of the length
      of chain remaining in the channel Lin(t) is measured. The entropic force is
      treated as the only parameter in fitting the solution of the nonlinear equation
      of motion of Lin(t) to the experimental data. The dependence of the entropic
      force on the width of the confining channel can be expressed as a power-law with
      an exponent of 1.3, which is consistent with the previous theoretical predictions
      for the entropy loss due to confinement. 

PMID- 24437918
TI  - Kinetic partitioning mechanism of HDV ribozyme folding.
AB  - RNA folding kinetics is directly tied to RNA biological functions. We introduce
      here a new approach for predicting the folding kinetics of RNA secondary
      structure with pseudoknots. This approach is based on our previous established
      helix-based method for predicting the folding kinetics of RNA secondary
      structure. In this approach, the transition rates for an elementary step: (1)
      formation, (2) disruption of a helix stem, and (3) helix formation with
      concomitant partial melting of an incompatible helix, are calculated with the
      free energy landscape. The folding kinetics of the Hepatitis delta virus (HDV)
      ribozyme and the mutated sequences are studied with this method. The folding
      pathways are identified by recursive searching the states with high net flux
      in(out) population starting from the native state. The theory results are in good
      agreement with that of the experiments. The results indicate that the bi-phasic
      folding kinetics for the wt HDV sequence is ascribed to the kinetic partitioning
      mechanism: Part of the population will quickly fold to the native state along the
      fast pathway, while another part of the population will fold along the slow
      pathway, in which the population is trapped in a non-native state. Single
      mutation not only changes the folding rate but also the folding pathway. 

PMID- 24437917
TI  - Kinks, loops, and protein folding, with protein A as an example.
AB  - The dynamics and energetics of formation of loops in the 46-residue N-terminal
      fragment of the B-domain of staphylococcal protein A has been studied. Numerical
      simulations have been performed using coarse-grained molecular dynamics with the
      united-residue (UNRES) force field. The results have been analyzed in terms of a
      kink (heteroclinic standing wave solution) of a generalized discrete nonlinear
      Schrodinger (DNLS) equation. In the case of proteins, the DNLS equation arises
      from a C(alpha)-trace-based energy function. Three individual kink profiles were
      identified in the experimental three-alpha-helix structure of protein A, in the
      range of the Glu16-Asn29, Leu20-Asn29, and Gln33-Asn44 residues, respectively;
      these correspond to two loops in the native structure. UNRES simulations were
      started from the full right-handed alpha-helix to obtain a clear picture of kink
      formation, which would otherwise be blurred by helix formation. All three kinks
      emerged during coarse-grained simulations. It was found that the formation of
      each is accompanied by a local free energy increase; this is expressed as the
      change of UNRES energy which has the physical sense of the potential of mean
      force of a polypeptide chain. The increase is about 7 kcal/mol. This value can
      thus be considered as the free energy barrier to kink formation in full alpha
      helical segments of polypeptide chains. During the simulations, the kinks emerge,
      disappear, propagate, and annihilate each other many times. It was found that the
      formation of a kink is initiated by an abrupt change in the orientation of a pair
      of consecutive side chains in the loop region. This resembles the formation of a
      Bloch wall along a spin chain, where the C(alpha) backbone corresponds to the
      chain, and the amino acid side chains are interpreted as the spin variables. This
      observation suggests that nearest-neighbor side chain-side chain interactions are
      responsible for initiation of loop formation. It was also found that the
      individual kinks are reflected as clear peaks in the principal modes of the
      analyzed trajectory of protein A, the shapes of which resemble the directional
      derivatives of the kinks along the chain. These observations suggest that the
      kinks of the DNLS equation determine the functionally important motions of
      proteins. 

PMID- 24437919
TI  - A cascade through spin states in the ultrafast haem relaxation of met-myoglobin.
AB  - We report on a study of the early relaxation processes of met-Myoglobin in
      aqueous solution, using a combination of ultrafast broadband fluorescence
      detection and transient absorption with a broad UV-visible continuum probe at
      different pump energies. Reconstruction of the spectra of the transient species
      unravels the details of the haem photocycle in the absence of photolysis. Besides
      identifying a branching in the ultrafast relaxation of the haem, we show clear
      evidence for an electronic character of the intermediates, contrary to the
      commonly accepted idea that the early time relaxation of the haem is only due to
      cooling. The decay back to the ground state proceeds partially as a cascade
      through iron spin states, which seems to be a general characteristic of haem
      systems. 

PMID- 24437920
TI  - Note: depletion potentials in non-additive asymmetric binary mixtures of hard
      spheres.

PMID- 24437921
TI  - Catalytically active nanomaterials: a promising candidate for artificial enzymes.
AB  - Natural enzymes, exquisite biocatalysts mediating every biological process in
      living organisms, are able to accelerate the rate of chemical reactions up to
      10(19) times for specific substrates and reactions. However, the practical
      application of enzymes is often hampered by their intrinsic drawbacks, such as
      low operational stability, sensitivity of catalytic activity to environmental
      conditions, and high costs in preparation and purification. Therefore, the
      discovery and development of artificial enzymes is highly desired. Recently, the
      merging of nanotechnology with biology has ignited extensive research efforts for
      designing functional nanomaterials that exhibit various properties intrinsic to
      enzymes. As a promising candidate for artificial enzymes, catalytically active
      nanomaterials (nanozymes) show several advantages over natural enzymes, such as
      controlled synthesis in low cost, tunability in catalytic activities, as well as
      high stability against stringent conditions. In this Account, we focus on our
      recent progress in exploring and constructing such nanoparticulate artificial
      enzymes, including graphene oxide, graphene-hemin nanocomposites, carbon
      nanotubes, carbon nanodots, mesoporous silica-encapsulated gold nanoparticles,
      gold nanoclusters, and nanoceria. According to their structural characteristics,
      these enzyme mimics are categorized into three classes: carbon-, metal-, and
      metal-oxide-based nanomaterials. We aim to highlight the important role of
      catalytic nanomaterials in the fields of biomimetics. First, we provide a
      practical introduction to the identification of these nanozymes, the source of
      the enzyme-like activities, and the enhancement of activities via rational design
      and engineering. Then we briefly describe new or enhanced applications of certain
      nanozymes in biomedical diagnosis, environmental monitoring, and therapeutics.
      For instance, we have successfully used these biomimetic catalysts as
      colorimetric probes for the detection of cancer cells, nucleic acids, proteins,
      metal ions, and other small molecules. In addition, we also introduce three
      exciting advances in the use of efficient modulators on artificial enzyme systems
      to improve the catalytic performance of existing nanozymes. For example, we
      report that graphene oxide could serve as a modulator to greatly improve the
      catalytic activity of lysozyme-stabilized gold nanoclusters at neutral pH, which
      will have great potential for applications in biological systems. We show that,
      through the incorporation of modulator into artificial enzymes, we can offer a
      facile but highly effective way to improve their overall catalytic performance or
      realize the catalytic reactions that were not possible in the past. We expect
      that nanozymes with unique properties and functions will attract increasing
      research interest and lead to new opportunities in various fields of research.

PMID- 24437922
TI  - Core-shell palladium nanoparticle@metal-organic frameworks as multifunctional
      catalysts for cascade reactions.
AB  - Uniform core-shell Pd@IRMOF-3 nanostructures, where single Pd nanoparticle core
      is surrounded by amino-functionalized IRMOF-3 shell, are prepared by a facile
      mixed solvothermal method. When used as multifunctional catalysts, the Pd@IRMOF-3
      nanocomposites exhibit high activity, enhanced selectivity, and excellent
      stability in the cascade reaction. Both experimental evidence and theoretical
      calculations reveal that the high catalytic performance of Pd@IRMOF-3
      nanocomposites originates from their unique core-shell structures. 

PMID- 24437925
TI  - Microsolvation of 1,4-butanediol: the competition between intra- and
      intermolecular hydrogen bonding.
AB  - The conformational space of 1,4-butanediol was examined at omegaB97X-D/6
      311+G(d,p). Of the 65 conformers examined, the seven lowest energy conformations
      have an internal hydrogen bond. The strength of this hydrogen bond is estimated
      to be 4 kcal mol(-1). A broad variety of microsolvated configurations of both the
      open form 5o and hydrogen-bonded form 5r of 1,4-butanediol involving one to four
      water molecules were located at omegaB97X-D/6-311+G(d,p). When one to three water
      molecules are included in the clusters, the lowest energy configurations involve
      the hydrogen-bonded form 5r. With four water molecules, configurations involving
      the open form 5o are favored enthalpically, but configurations with the hydrogen
      bonded form 5r are the lowest in free energy. These calculations suggest that
      both 5r and 5o will coexist in aqueous solution. 

PMID- 24437924
TI  - Molecular characterization and functional analysis of outer membrane vesicles
      from the antarctic bacterium Pseudomonas syringae suggest a possible response to
      environmental conditions.
AB  - Outer membrane vesicles (OMVs) of Gram-negative bacteria form an important aspect
      of bacterial physiology as they are involved in various functions essential for
      their survival. The OMVs of the Antarctic bacterium Pseudomonas syringae Lz4W
      were isolated, and the proteins and lipids they contain were identified. The
      matrix-assisted laser desorption/ionization time of flight (MALDI-TOF/TOF)
      analysis revealed that phosphatidylethanolamines and phosphatidylglycerols are
      the main lipid components. The proteins of these vesicles were identified by
      separating them by one-dimensional gel electrophoresis and liquid chromatography
      coupled to electrospray ionization tandem mass spectrometry (ESI-MS/MS). They are
      composed of outer membrane and periplasmic proteins according to the subcellular
      localization predictions by Psortb v.3 and Cello V2.5. The functional annotation
      and gene ontology of these proteins provided hints for various functions
      attributed to OMVs and suggested a potential mechanism to respond to the
      extracellular environmental changes. The OMVs were found to protect the producer
      organism against the membrane active antibiotics colistin and melittin but not
      from streptomycin. The 1-N-phenylnapthylamine (NPN)-uptake assay revealed that
      the OMVs protect the bacterium from membrane active antibiotics by scavenging
      them and also showed that membrane and protein packing of the OMVs was similar to
      the parent bacterium. The sequestering depends on the composition and
      organization of lipids and proteins in the OMVs. 

PMID- 24437926
TI  - Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic
      acid-conjugated nanoparticles.
AB  - The incorporation of a high percentage of targeting molecules into drug delivery
      system is one of the important methods for improving efficacy of targeting
      therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic
      acid (FA) as targeting molecule have a low targeting efficiency due to a low FA
      conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using
      a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of
      46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate
      therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro
      experiments, an IC50 of 5.69 ug/mL has been achieved for 5-FU loaded PLGA-1, 3
      diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is
      significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which
      only have an IC50 of 22.9 and 14.17 ug/mL, respectively. The fluorescent
      microscopy images showed that nanoparticles with FA are largely taken up by HT-29
      cancer cells and the targeting nanoparticles have more affinity to cancer cells
      than the pure drugs and untreated nanoparticles. Therefore, the 1, 3
      diaminopropane can facilitate the conjugation of FA to PLGA to form a novel
      polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be
      a highly efficient system for specific delivery of drugs to cancer cells.

PMID- 24437928
TI  - Determination of six illegal antibiotics in chicken jerky dog treats.
AB  - In 2007 chicken jerky dog treats were implicated in causing illnesses and death
      in dogs in several countries. Affected dogs were diagnosed with acquired Fanconi
      syndrome, which is characterized by kidney malfunction. Known causes of this
      condition include a chemical assault by various contaminants including certain
      drugs. For this reason investigations into possible causes of the illnesses
      included antibiotics that may be used in animal husbandry. Targeted analyte
      screens of individual imported chicken jerky dog treats using LC-MS/MS detected
      six illegal antibiotics in imported products of several brands. Trimethoprim,
      tilmicosin, enrofloxacin, sulfaclozine, and sulfamethoxazole are not allowed in
      chicken at any level and were found as high as 2800 ng/g (ppb). Sulfaquinoxaline
      was found in chicken jerky treats as high as 800 ng/g, which is well above the
      U.S. FDA tolerance of 100 ng/g. Although there is no evidence these contaminants
      were responsible for the dog illnesses, their misuse could contribute to
      antibiotic-resistant strains of bacteria. 

PMID- 24437929
TI  - Structural and spectroscopic studies of fluoroprotactinates.
AB  - Seven protactinium(V) fluoride compounds have been synthesized, and their crystal
      structures and Raman spectra are reported. (NH4)2PaF7, K2PaF7, Rb2PaF7, and
      Cs2PaF7 were found to crystallize in the monoclinic space group P21/c for the
      ammonium compound and C2/c for the K(+)-, Rb(+)-, and Cs(+)-containing compounds,
      with nine-coordinate Pa forming infinite chains through fluorine bridges. Na3PaF8
      crystallizes in the tetragonal space group I4/mmm with eight-coordinate Pa in
      tetragonal geometry, while tetramethylammonium fluoroprotactinate shows two
      different structures: (Me4N)2(H3O)PaF8, an eight-coordinate molecular compound
      crystallizing in the monoclinic space group C2/c, and (Me4N)PaF6, an eight
      coordinate Pa compound forming infinite chains and crystallizing in the
      orthorhombic space group Pnnm. A comparison of solid- and solution-state Raman
      data indicates that the PaF8(-) anion could be the predominant Pa(V) complex in
      concentrated solutions of aqueous HF. 

PMID- 24437932
TI  - Radon and thoron levels, their spatial and seasonal variations in adobe dwellings
      - a case study at the great Hungarian plain.
AB  - Radon and thoron isotopes are responsible for approximately half of the average
      annual effective dose to humans. Although the half-life of thoron is short, it
      can potentially enter indoor air from adobe walls. Adobe was a traditional
      construction material in the Great Hungarian Plain. Its major raw materials are
      the alluvial sediments of the area. Here, seasonal radon and thoron activity
      concentrations were measured in 53 adobe dwellings in 7 settlements by pairs of
      etched track detectors. The results show that the annual average radon and thoron
      activity concentrations are elevated in these dwellings and that the proportions
      with values higher than 300 Bq m(-3) are 14-17 and 29-32% for radon and thoron,
      respectively. The calculated radon inhalation dose is significantly higher than
      the world average value, exceeding 10 mSv y(-1) in 7% of the dwellings of this
      study. Thoron also can be a significant contributor to the inhalation dose with
      about 30% in the total inhalation dose. The changes of weather conditions seem to
      be more relevant in the variation of measurement results than the differences in
      the local sedimentary geology. Still, the highest values were detected on clay.
      Through the year, radon follows the average temperature changes and is affected
      by the ventilation, whereas thoron rather seems to follow the amount of
      precipitation.

PMID- 24437935
TI  - Protective effects of ETC complex III and cytochrome c against hydrogen peroxide
      induced apoptosis in yeast.
AB  - In mammals, the mitochondrial electron transfer components (ETC) complex III and
      cytochrome c (cyt c) play essential roles in reactive oxygen species (ROS)
      induced apoptosis. However, in yeast, the functions of cyt c and other ETC
      components remain unclear. In this study, three ETC-defective yeast mutants
      qcr7Delta, cyc1Deltacyc7Delta, and cox12Delta, lacking cyt c oxidoreductase
      (complex III), cyt c, and cyt c oxidase (complex IV), respectively, were used to
      test the roles of these proteins in the response of cells to hydrogen peroxide
      (H2O2). Mutants qcr7Delta and cyc1Deltacyc7Delta displayed greater H2O2
      sensitivity than the wild-type or cox12Delta mutant. Consistent with this,
      qcr7Delta and cyc1Deltacyc7Delta produced higher ROS levels, displayed
      derepressed expression of the proapoptotic genes AIF1, NUC1, and NMA111, but not
      YCA1, at the mRNA level, and were more vulnerable to H2O2-induced apoptosis.
      Interestingly, mutants lacking these proapoptotic genes displayed enhanced H2O2
      tolerance, but unaffected ROS accumulation. Furthermore, the overexpression of
      antiapoptotic genes (Bcl-2, Ced-9, AtBI-1, and PpBI-1) reduced the levels of
      AIF1, NUC1, and NMA111 mRNAs, and reduced H2O2-induced cell death. Our findings
      identify two ETC components as early-inhibitory members of the ROS-mediated
      apoptotic pathway, suggesting their essential roles in metabolizing H2O2,
      probably by providing reduced cyt c, allowing cyt c peroxidase to remove H2O2
      from the cells.

PMID- 24437936
TI  - Simplified pretubulysin derivatives and their biological effects on cancer cells.
AB  - Tubulin binding agents are a potent group of cancer chemotherapeutics. Most of
      these substances are naturally derived compounds. A novel substance class of
      destabilizing agents is the group of tubulysins. The tubulysins and their
      derivative pretubulysin have shown high efficacy in vitro and in vivo. Due to
      their complex chemical structures, one major bottleneck of the tubulysins is
      their accessibility. Biotechnological as well as chemical production is
      challenging, especially on larger scales. Thus, the synthesis of chemically
      simplified structures is needed with retained or improved biological activity.
      Herein is presented the biological evaluation of two pretubulysin derivatives [2
      desmethylpretubulysin AU816 (1) and phenylpretubulysin JB337 (2)] in comparison
      to pretubulysin. Both 1 and 2 display a simplification in chemical synthesis. It
      was shown that both compounds exhibited potent biological activity against cancer
      cells. These simplified compounds inhibited tubulin polymerization in the
      nanomolar range. The cytotoxic effects of 1 and 2 were in a similar range, when
      compared with pretubulysin [IC50 (nM): pretubulysin: 0.6; 1: 10; 2: 100].
      Furthermore, it was shown that cell cycle arrest is induced and migration is
      hampered in MDA-MB-231 breast cancer cells. In conclusion, 1 was shown to be
      about 10-fold more active than 2 and as potent as pretubulysin. 

PMID- 24437937
TI  - Universal surface-enhanced Raman scattering amplification detector for
      ultrasensitive detection of multiple target analytes.
AB  - Up to now, the successful fabrication of efficient hot-spot substrates for
      surface-enhanced Raman scattering (SERS) remains an unsolved problem. To address
      this issue, we describe herein a universal aptamer-based SERS biodetection
      approach that uses a single-stranded DNA as a universal trigger (UT) to induce
      SERS-active hot-spot formation, allowing, in turn, detection of a broad range of
      targets. More specifically, interaction between the aptamer probe and its target
      perturbs a triple-helix aptamer/UT structure in a manner that activates a
      hybridization chain reaction (HCR) among three short DNA building blocks that
      self-assemble into a long DNA polymer. The SERS-active hot-spots are formed by
      conjugating 4-aminobenzenethiol (4-ABT)-encoded gold nanoparticles with the DNA
      polymer through a specific Au-S bond. As proof-of-principle, we used this
      approach to quantify multiple target analytes, including thrombin, adenosine, and
      CEM cancer cells, achieving lowest limit of detection values of 18 pM, 1.5 nM,
      and 10 cells/mL, respectively. As a universal SERS detector, this prototype can
      be applied to many other target analytes through the use of suitable DNA
      functional partners, thus inspiring new designs and applications of SERS for
      bioanalysis. 

PMID- 24437942
TI  - Discovery of a phosphor for light emitting diode applications and its structural
      determination, Ba(Si,Al)5(O,N)8:Eu2+.
AB  - Most of the novel phosphors that appear in the literature are either a variant of
      well-known materials or a hybrid material consisting of well-known materials.
      This situation has actually led to intellectual property (IP) complications in
      industry and several lawsuits have been the result. Therefore, the definition of
      a novel phosphor for use in light-emitting diodes should be clarified. A recent
      trend in phosphor-related IP applications has been to focus on the novel
      crystallographic structure, so that a slight composition variance and/or the
      hybrid of a well-known material would not qualify from either a scientific or an
      industrial point of view. In our previous studies, we employed a systematic
      materials discovery strategy combining heuristics optimization and a high
      throughput process to secure the discovery of genuinely novel and brilliant
      phosphors that would be immediately ready for use in light emitting diodes.
      Despite such an achievement, this strategy requires further refinement to prove
      its versatility under any circumstance. To accomplish such demands, we improved
      our discovery strategy by incorporating an elitism-involved nondominated sorting
      genetic algorithm (NSGA-II) that would guarantee the discovery of truly novel
      phosphors in the present investigation. Using the improved discovery strategy, we
      discovered an Eu(2+)-doped AB5X8 (A = Sr or Ba, B = Si and Al, X = O and N)
      phosphor in an orthorhombic structure (A21am) with lattice parameters a =
      9.48461(3) A, b = 13.47194(6) A, c = 5.77323(2) A, alpha = beta = gamma = 90
      degrees , which cannot be found in any of the existing inorganic compound
      databases. 

PMID- 24437940
TI  - Crosstalk between phosphodiesterase 7 and glycogen synthase kinase-3: two
      relevant therapeutic targets for neurological disorders.
AB  - Chronic neuroinflammation has been increasingly recognized as a primary mechanism
      underlying acute brain injury and neurodegenerative diseases. Enhanced expression
      of diverse pro-inflammatory agents in glial cells has been shown to contribute to
      the cell death that takes place in these disorders. Previous data from our group
      have shown that different inhibitors of the cyclic adenosine monophosphate (cAMP)
      specific phosphodiesterase 7 (PDE7) and glycogen synthase kinase-3 (GSK-3)
      enzymes are potent anti-inflammatory agents in different models of brain injury.
      In this study, we investigated cross-talk between PDE7 and GSK-3, two relevant
      therapeutic targets for neurological disorders, using a chemical approach. To
      this end, we compared specific inhibitors of GSK-3 and PDE7 with dual inhibitors
      of both enzymes with regard to anti-inflammatory effects in primary cultures of
      glial cells treated with lipopolysaccharide. Our results show that the GSK-3
      inhibitors act exclusively by inhibition of this enzyme. By contrast, PDE7
      inhibitors exert their effects via inhibition of PDE7 to increase intracellular
      cAMP levels but also through indirect inhibition of GSK-3. Activation of protein
      kinase A by cAMP results in phosphorylation of Ser9 of GSK-3 and subsequent
      inhibition. Our results indicate that the indirect inhibition of GSK-3 by PDE7
      inhibitors is an important mechanism that should be considered in the future
      development of pharmacological treatments. 

PMID- 24437943
TI  - Stability of hemi-bonded vs proton-transferred structures of (H2O)2(+),
      (H2S)2(+), and (H2Se)2(+) studied with projected Hartree-Fock methods.
AB  - Hartree-Fock (HF) is known to suffer from drawbacks in the description of the
      relative stabilities between the hemi-bonded (HB) and proton-transferred (PT)
      isomers of the water dimer cation, (H2O)2(+). The energy difference predicted by
      HF is too large, approximately 27 kcal/mol, which is lowered to 7 kcal/mol when
      correlation effects are added. The error in HF has been previously attributed to
      the large dynamic correlation effects in the HB structure as well to the large
      symmetry breaking this structure exhibits. In this study we use the recently
      developed projected Hartree-Fock (PHF) methods to study the relative stability of
      the two isomers of (H2O)2(+) as well as its second and third row analogs, namely,
      (H2S)2(+) and (H2Se)2(+). In PHF, symmetries are broken and restored in a
      variation-after-projection approach and thus can deal easily with systems for
      which HF itself spontaneously breaks symmetry. We use different flavors of PHF
      (SUHF, KSUHF, SGHF, and KSGHF) to explore their ability in capturing dynamic
      correlation effects and to compare their performance to different wave function
      based methods. We study the role of the symmetry-breaking in the above systems,
      using wave function based methods with unrestricted and restricted wave functions
      as well as performing a single-shot symmetry restoration (a projection-after
      variation scheme). 

PMID- 24437944
TI  - Notoginsenoside R1-mediated neuroprotection involves estrogen receptor-dependent
      crosstalk between Akt and ERK1/2 pathways: a novel mechanism of Nrf2/ARE
      signaling activation.
AB  - Notoginsenoside R1 (NGR1), a novel phytoestrogen isolated from Panax notoginseng,
      has antioxidant and anti-apoptotic properties. Oxidative stress plays a pivotal
      role in neurodegenerative diseases. To mimic oxidative stress in neurons and
      explore the neuroprotection of NGR1, H2O2-induced neurotoxicity in NGF-induced
      differentiation of PC12 cells was used. In this study, NGR1 preconditioning
      provided neuroprotective effects via suppressing H2O2-induced the intracellular
      ROS accumulation, the increase in the product of lipid peroxidation (MDA),
      protein oxidation (protein carbonyl), and DNA fragmentation (8-OHdG), and
      mitochondrial membrane depolarization as well as caspase-3 activation. Moreover,
      NGR1 treatment alone potently increased the nuclear translocation of Nrf2,
      augmented ARE enhancer activity, and upregulated the expression and activity of
      phase II antioxidant enzymes including HO-1, NQO-1, and gamma-GCSc. NGR1 could
      also increase the ERE activity and activate Akt and ERK1/2 pathways. NGR1
      mediated activation of Nrf2/ARE signaling and neuroprotection were abolished by
      genetic silencing of Nrf2 using siRNA or the pharmacological blockade of estrogen
      receptors using ICI-182780, and partially inhibited by Akt siRNA or ERK siRNA
      transfection. In addition, the phosphorylation of ERK1/2 mediated by NGR1 was
      markedly inhibited in PC12 cells transfected with Akt siRNA. On the contrary,
      ERK1/2 siRNA transfection hardly had any effect on the phosphorylation of Akt
      mediated by NGR1. NGR1-mediated activation of Akt and ERK1/2 pathways was blocked
      by ICI-182780. In conclusion, NGR1 provided neuroprotection via inducing an
      estrogen receptor-dependent crosstalk between Akt and ERK1/2 pathways,
      subsequently activating Nrf2/ARE signaling and thereby up-regulating phase II
      antioxidant enzymes.

PMID- 24437945
TI  - Development and analytical evaluation of a spectrophotometric procedure for the
      quantification of different types of phosphorus in meat products.
AB  - Phosphorus is an important natural nutrient, but high dietary phosphorus intake,
      including that sourced from added preservatives, is of great concern in renal
      patients. In this context a reliable analytical method able to quantify
      differential phosphorus in food could be a valuable tool for monitoring diet
      composition This paper presents a novel analytical procedure to quantify the
      following kinds of phosphorus in cooked ham: total (TP), inorganic (IP), from
      phospholipids (PL), and from phosphoproteins (PP). This technique is based on a
      suitable sample preparation followed by spectrophotometric analyses. Analytical
      performances of each method were evaluated, taking advantage also of food
      industry certified material and in-house reference samples. Limit of detection
      and limit of quantification values for TP, IP, PP-derived, and PL-derived
      phosphorus were 13 and 37, 11 and 33, 2 and 20, and 6 and 16 mg P/100 g fresh
      mass, respectively. Similar results were obtained when this procedure was used to
      quantify different types of phosphorus present in cooked ham samples. In
      conclusion, this procedure is effective for quantifying the content of different
      types of phosphorus present in cooked ham, which can be contributed by different
      phosphorus-containing ingredients and additives. To the best of the authors'
      knowledge, this is the first time that simultaneous determination of TP, IP, PL,
      and PP in cooked ham has been reported. 

PMID- 24437949
TI  - Interaction of antidiabetic vanadium compounds with hemoglobin and red blood
      cells and their distribution between plasma and erythrocytes.
AB  - The interaction of V(IV)O(2+) ion with hemoglobin (Hb) was studied with the
      combined application of spectroscopic (EPR), spectrophotometric (UV-vis), and
      computational (DFT methods) techniques. Binding of Hb to V(IV)O(2+) in vitro was
      proved, and three unspecific sites (named alpha, beta, and gamma) were
      characterized, with the probable coordination of His-N, Asp-O(-), and Glu-O(-)
      donors. The value of log beta for (VO)Hb is 10.4, significantly lower than for
      human serum apo-transferrin (hTf). In the systems with V(IV)O potential
      antidiabetic compounds, mixed species cis-VOL2(Hb) (L = maltolate (ma), 1,2
      dimethyl-3-hydroxy-4(1H)-pyridinonate (dhp)) are observed with equatorial binding
      of an accessible His residue, whereas no ternary complexes are observed with
      acetylacetonate (acac). The experiments of uptake of [VO(ma)2], [VO(dhp)2], and
      [VO(acac)2] by red blood cells indicate that the neutral compounds penetrate the
      erythrocyte membrane through passive diffusion, and percent amounts higher than
      50% are found in the intracellular medium. The biotransformation of [VO(ma)2],
      [VO(dhp)2], and [VO(acac)2] inside the red blood cells was proved. [VO(dhp)2]
      transforms quantitatively in cis-VO(dhp)2(Hb), [VO(ma)2] in cis-VO(ma)2(Hb), and
      cis-VO(ma)2(Cys-S(-)), with the equatorial coordination of a thiolate-S(-) of GSH
      or of a membrane protein, and [VO(acac)2] in the binary species (VO)xHb and two
      V(IV)O complexes with formulation VO(L(1),L(2)) and VO(L(3),L(4)), where L(1),
      L(2), L(3), and L(4) are red blood cell bioligands. The results indicate that, in
      the studies on the transport of a potential pharmacologically active V species,
      the interaction with red blood cells and Hb cannot be neglected, that a
      distribution between the erythrocytes and plasma is achieved, and that these
      processes can significantly influence the effectiveness of a V drug. 

PMID- 24437950
TI  - Emerging techniques in molecular detection of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) are increasingly recognized for their potential
      utility in cancer diagnosis and prognosis. Emerging technologies in the past
      decade have allowed possible isolation and characterization of CTCs in the
      peripheral blood of cancer patients, including immunomagnetic technique coupled
      with immunofluorescence methodology, microfluidic platform, x-ray imaging
      technique and flow cytometry, filter-adapted FISH and miRNA microarray. Although
      there are still a number of challenges associated with the identification and
      molecular characterization of CTCs, the analysis of CTCs carries important
      prognostic and therapeutic implications for personalized cancer management. 

PMID- 24437951
TI  - Total synthesis and structural revision of (+)-cristatumin C.
AB  - Naturally occurring (+)-cristatumin C, a bis-pyrrolidinoindoline diketopiperazine
      alkaloid isolated from Eurotium cristatum EN-220, is the
      2R,3R,11S,15R,2'R,3'R,11'S,15'S enantiomer, as confirmed by total synthesis. 

PMID- 24437954
TI  - A turn-key approach for large-scale identification of complex posttranslational
      modifications.
AB  - The conjugation of complex post-translational modifications (PTMs) such as
      glycosylation and Small Ubiquitin-like Modification (SUMOylation) to a substrate
      protein can substantially change the resulting peptide fragmentation pattern
      compared to its unmodified counterpart, making current database search methods
      inappropriate for the identification of tandem mass (MS/MS) spectra from such
      modified peptides. Traditionally it has been difficult to develop new algorithms
      to identify these atypical peptides because of the lack of a large set of
      annotated spectra from which to learn the altered fragmentation pattern. Using
      SUMOylation as an example, we propose a novel approach to generate large MS/MS
      training data from modified peptides and derive an algorithm that learns
      properties of PTM-specific fragmentation from such training data. Benchmark tests
      on data sets of varying complexity show that our method is 80-300% more sensitive
      than current state-of-the-art approaches. The core concepts of our method are
      readily applicable to developing algorithms for the identifications of peptides
      with other complex PTMs. 

PMID- 24437955
TI  - [Wet form age-related macular degeneration two years treatment results using anti
      VEGF drugs].
AB  - AIM: The aim of the study was to establish the efficacy of anti VEGF (Vascular
      Endothelial Growing Factor) drugs in the treatment of wet form ARMD (Age-Related
      Macular Degeneration) in everyday clinical practice in the Department of
      Ophthalmology, Faculty Hospital, Hradec Kralove, Czech Republic, E.U., in
      patients registered in the Czech national registry AMADEUS. MATERIAL AND METHODS:
      Retrospective study with 24 months follow-up period. In the group were evaluated
      143 eyes of 140 patients, out of them were 77 women (65.8 %), of average age
      73.09 (71.69 - 74.48) years, and 40 men (34.2 %) of average age 74 (58 - 85)
      years. All of the patients were completely examined before the beginning of the
      treatment; during the treatment were, except the standardized eye examination, in
      patients treated with ranibizumab the color fundus photography and Optical
      Coherence Tomography (OCT) with measuring of the central retinal thickness
      performed every three months at least. The patients treated by pegaptanib were
      examined every six weeks before the drug application. The fluorescence
      angiography (FA) was performed at the beginning of the treatment to establish the
      type and extension of the choroidal neovascularization and during the treatment
      in case of necessity to establish the activity of the choroidal neovascular
      membrane (CNV). The treatment by ranibizumab was in the regimen PRN (pro re
      nata), and pegaptanib was applied every six months during the first year with the
      follow-up evaluation of the findings. The treatment evaluations were performed at
      12 and 24 months. RESULTS: During the two years follow - up period, the authors
      noticed in patients treated with ranibizumab loss of 5.12 letters of ETDRS
      optotypes in case of mostly classical CNV, in occult CNV loss of 5.45 letters,
      and in minimally classical CNV loss of 2.83 letters. In three evaluated eyes with
      classical CNV in patients treated with pegaptanib we noticed after 2 years loss
      of 6.67 letters, in eleven eyes with occult CNV we established loss of 9.91
      letters, and in two eyes with minimally classical CNV the average best-corrected
      visual acuity (BCVA) remained unchanged. The pegaptanib treatment results may be
      influenced by small number of evaluated patients. The visual acuity changes
      during the two years treatment were not statistically significant. We noticed the
      decrease of average CRT (central retinal thickness) in all types of CNV treated
      both with ranibizumab and pegaptanib after the two years follow up. To reach
      these results, an average of 5.51 applications of ranibizumab and 9 applications
      of pegaptanib during the two years were used. CONCLUSION: In the followed-up
      group we found, comparing to the natural course of neovascular form of ARMD,
      retarding of the BCVA decrease during the two years treatment with VEGF
      inhibitors in everyday clinical practice. Better results were achieved with
      ranibizumab treatment, however the differences were not statistically
      significant. Key words: age related macular degeneration, AMADEUS Czech national
      registry, ranibizumab, pegaptanib.

PMID- 24437956
TI  - [Surgical treatment of the idiopatic macular hole - our experience].
AB  - AIM: To evaluate the results of the idiopathic macular hole (IDM) surgical
      treatment. Surgery included pars plana vitrectomy (PPV) with the removal
      (peeling) of internal limiting membrane (ILM) and intraocular tamponade with a
      diluted expanding gas. MATERIAL AND METHODS: A retrospective study included 100
      eyes of 96 patients (10 men and 86 women) with IDM, that were operated at II. Eye
      Clinic SZU in Banska Bystrica from August 2008 to August 2012. Patients age
      ranged from 48 to 86 years, average 69.3 years. Mean follow-up time was 39.2
      months. All patients underwent PPV with the ILM peeling. Intraocular air
      tamponade was used in 1-case, 16 % SF6 84-times and 12 % C3F8 15 times. RESULTS:
      Anatomical success of the operation was evaluated with OCT examination. After
      primary operation there were 92 (92 %) closed macular holes in our study. In 6
      patients (6 %), we decided to reoperate with gas tamponade (SF6 2-times, C3F8 4
      times). After the reoperations final anatomical success in our study was 97 eyes
      (97 %). Functional results we examined with Snellen. Improved best corrected
      visual acuity (BCVA) was observed in 85 eyes (85 %), no changes in 11 eyes (11
      %), and deterioration in 4 eyes (4 %). Improvement in vision was following: 1
      line - 18 eyes, 2 lines - 20 eyes, 3 lines - 18 eyes, 4 lines - 11 eyes, 5 or
      more lines in 18 eyes. CONCLUSION: Pars plana vitrectomy with ILM peeling and gas
      tamponade is highly effective and safe treatment of idiopathic macular hole.Key
      words: idiopathic macular hole, pars plana vitrectomy, expanding gas.

PMID- 24437957
TI  - [New methods of the treatment of retinal dystrophies].
AB  - There is a brief review of actual treatment possibilities of retinal dystrophies
      in this article. Vitaminotherapy, electrostimulation and gene therapy are used in
      beginning stages of disorders. The efficiency of neuroprotective substances that
      are applied intravitreally using encapsulated cell technology is examined, as
      well as influence of systemic immunotherapy. In advanced stages of retinal
      diseases that are connected with loss of photoreceptors are used electronic
      retinal prostheses. Effectivity of treatment with stem cells, transplantation of
      cells and tissues and optogenetic therapy are evaluated. Key words: new
      therapeutic methods, retinal dystrophy. 

PMID- 24437958
TI  - [Efficiency evaluation of non-infectious uveitis].
AB  - Authors compared clinical and economic effeciency of treatment of the classical
      corticosteroids therapy and modern immunosuppressive treatment or their
      combination. Retrospective evaluation carried out in 2012, covering 2006-2011,
      monitored sample of 27 patients, 16 women and 11 men, 45 eyes with disabilities.
      The average age in the last year of follow-up monitoring was 30.2, ranging from
      14 to 76 years. The mean duration of disease for the whole sample is 16.5 years
      with a range from 6 to 36 years. Three basic diagnoses were included in
      investigated group: chronic iridocyclitis in 59 % of eyes, intermediate uveitis
      in 30 % of eyes and sympathetic ophthalmia in 11 % of eyes. The optimal treatment
      not be determined, however, combined corticosteroid sparing therapy was the most
      beneficial to maintain in terms of visual acuity with minimal side effects and
      cost effectiveness. Successful outcomes of treatment were observed for
      intermediate uveitis, because the visual acuity improved in nine letetters of
      ETDRS chart in the study. Satisfactory treatment was proved in chronic
      iridocyclitis and sympathetic ophthalmia in general, because visual acuity
      improved in a few letters of ETDRS chart, in the same line as in the beginning of
      the six-year follow-up. Rounded average annual prize for treatment including
      pharmacotherapy, outpatient and inpatient care and laboratory follow-up was in
      chronic iridocyclitis ? 990, in intermediate uveitis ? 310 and sympathetic
      ophthalmia ? 1550. Pharmacotherapy exceeded the financial appraisal of
      specialized medical and inpatient care in total cost. Key words: uveitis,
      corticosteorids, immunosuppression, costeffectivness. 

PMID- 24437959
TI  - [Glaucoma therapy - current overview of data and information].
AB  - The authors submit the overview of the actual situation in the glaucoma therapy.
      They follow up the trends in antiglaucomatic treatment in the last period
      including financial aspects of medicament and surgical treatment. Attention is
      paid especially to medicaments management, actual overview of available
      antiglaucomatic drugs, function and position of generic drugs and differences
      among them, the daily dose of benzalconium chloride in glaucoma treatment, actual
      average of patients supplementary payments at the drug purchase in the pharmacy,
      surgical treatment costs and legal issues. Pharmacologists viewpoints and the
      Czech State Drug Control Authority (SUKL) opinions complete the professionals
      point of the view and facilitate his/her complete orientation in glaucoma therapy
      issues. Key words: glaucoma, prescription, surgical treatment, treatment costs,
      legal issues. 

PMID- 24437960
TI  - [The potential use of honey in ophthalmology].
AB  - Honey is considered to be a natural product with antibacterial and anti
      inflammatory properties. Its successful application in the treatment of chronic
      wounds and burns has promoted its further clinical use in other clinical
      departments, including ophthalmology. One of the major advantages of honey is its
      multi-factorial antibacterial action and the fact that there is no risk of
      developing bacterial resistance to it. In this work we discuss the current
      knowledge and new perspectives for honey therapy in treatment of eye diseases
      such as dry eye disease, age-related macular degeneration, cataracts and bullous
      keratopathy. Key words: honey, eye diseases, natural product, treatment. 

PMID- 24437961
TI  - [Late metastasis development in two cases of small choroidal melanoma].
AB  - PURPOSE: To present data pointing out that small tumour size might not be a
      sufficient predictor of good prognosis of choroidal melanoma and present a new
      promising therapy of hepatic metastasis. METHODS: Retrospective, noncomparative
      case report of two patients with small choroidal melanoma. RESULTS: Two cases of
      small choroidal melanoma which developed metastases are described. Both patients
      underwent radiotherapy of the primary tumour. Metastases were treated by combined
      therapy in patient 1 while in patient 2 a new therapeutic modality of
      stereotactic radiotherapy, Cyberknife, was applied. Patient 1 died from
      metastatic spread 7,6 years after primary therapy despite a very good local
      tumour control. Patient 2 died 11,3 years after primary therapy due to
      intercurrent disease with a very good local eye findings and hepatic metastasis
      in regression. CONCLUSION: Choroidal melanoma of a small size can develop into
      metastatic disease even long time after satisfactory primary treatment. Further
      studies are required to assess the risk factors of metastatic spread in small
      uveal melanomas. Cyberknife stereotactic radiotherapy seems to be a promising
      therapeutic method of a solitary hepatic metastasis. Key words: choroidal
      melanoma, metastasis, prognostic factors, stereotactic radiotherapy.

PMID- 24437962
TI  - Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal
      antibodies against Cx43 and BSAT1.
AB  - Targeted drug delivery for brain tumor treatment is one of the important
      objectives in nanomedicine. Human glioblastoma is the most frequent and
      aggressive type of brain tumors. The preferential expression of membrane protein
      connexin 43 (Cx43) and brain-specific anion transporter (BSAT1) in the tumor and
      peritumoral area is a key component for targeted drug delivery. The purpose of
      this study was to design cisplatin-loaded nanogels conjugated with monoclonal
      antibodies to Cx43 and BSAT1 for treatment of intracranial gliomas 101/8. MRI
      volumetric analysis of tumor-bearing rats indicated significantly reduced tumor
      volume with cisplatin-loaded targeted-nanogel treatment compared to other
      formulations. The median survival of rats treated with targeted nanogels
      conjugated with specific mAbs against extracellular loops of Cx43 and BSAT1 were
      27 and 26.6 days higher than that in control group, respectively. For the first
      time we demonstrated the efficiency of mAb-targeted cisplatin-loaded nanogels in
      the experimental model of glioma 101/8. This approach could facilitate the
      development of new drug delivery systems for the treatment of gliomas.

PMID- 24437963
TI  - Photoemission mechanism of water-soluble silver nanoclusters: ligand-to-metal
      metal charge transfer vs strong coupling between surface plasmon and emitters.
AB  - Using carboxylate-protected silver nanoclusters (Ag-carboxylate NCs) as a model,
      we separately investigated the contribution of the ligand shell and the metal
      core to understand the nature of photoluminescence of Ag NCs. A new
      Ag(0)NCs@Ag(I)-carboxylate complex core-shell structural model has been proposed.
      The emission from the Ag-carboxylate NCs could be attributed to ligand-to-metal
      metal charge transfer from Ag(I)-carboxylate complexes (the oxygen atom in the
      carboxylate ligands to the Ag(I) ions) to the Ag atoms and subsequent radiative
      relaxation. Additionally, we found that the emission wavelength of the Ag NCs
      depends on the excitation wavelength implying a strong coupling between surface
      plasmon and emitter in Ag NCs. The strong coupling between the surface plasmon
      and the emitter determines the quantum yield and lifetime. The emission mechanism
      of Ag NCs and its relation to the organic templates and metal cores were clearly
      clarified. The results should stimulate additional experimental and theoretical
      research on the molecular-level design of luminescent metal probes for
      optoelectronics and other applications. 

PMID- 24437965
TI  - Artificial sensing intelligence with silicon nanowires for ultraselective
      detection in the gas phase.
AB  - The use of molecularly modified Si nanowire field effect transistors (SiNW FETs)
      for selective detection in the liquid phase has been successfully demonstrated.
      In contrast, selective detection of chemical species in the gas phase has been
      rather limited. In this paper, we show that the application of artificial
      intelligence on deliberately controlled SiNW FET device parameters can provide
      high selectivity toward specific volatile organic compounds (VOCs). The obtained
      selectivity allows identifying VOCs in both single-component and multicomponent
      environments as well as estimating the constituent VOC concentrations. The effect
      of the structural properties (functional group and/or chain length) of the
      molecular modifications on the accuracy of VOC detection is presented and
      discussed. The reported results have the potential to serve as a launching pad
      for the use of SiNW FET sensors in real-world counteracting conditions and/or
      applications. 

PMID- 24437966
TI  - Effective and reusable monolith capillary trap of nitrosamine extraction by
      superheated water from frankfurter sausage.
AB  - A novel, simple, rapid, and inexpensive method of extraction and cleanup of
      nitrosamines from frankfurter sausage was achieved with a capillary filled with
      monolith of either polystyrene-co-divinylbenzene (PS-DVB), Polydivinylbenzene (P
      DVB), or silica that had been fabricated. The study of capability in trapping
      nonpolar matrix and monolith capillaries with varied lengths revealed that a
      silica monolith gave the best result for nitrosamine determination. With an
      online coupling between superheated water extraction (SWE) and silica monolith
      capillary connected to a 5% phenyl-methylpolysiloxane column, factors affecting
      the extraction and determination, namely, sensitivity with and without the
      monolith, reusability, injection-injection repeatability, capillary-capillary
      precision, and chromatographic separation, were investigated. This confirmed the
      feasibility of the method. The optimal length of silica monolith capillary was 30
      mm, offering reuse more than 20 times. Separation and quantification of selected
      volatile nitrosamines were carried out using gas chromatography (GC) coupled with
      either a flame ionization detector (FID) or mass spectrometer (MS). The overall
      extraction and determination method determined by GC-MS allowed for a recovery of
      75-88% with a <5% relative standard deviation (RSD) and detection limit of 2-5 ng
      of injected nitrosamine. 

PMID- 24437970
TI  - Investigation on CD inversion at visible region caused by a tilt of the pi
      conjugated substituent: theoretical and experimental approaches by using an
      asymmetric framework of diarylethene annulated isomer.
AB  - A substituent effect of asymmetric diarylethene annulated isomer on their
      chiroptical properties was investigated by means of theoretical and experimental
      approaches. The absolute configuration of the annulated isomer was determined by
      X-ray structural analysis and DFT calculation. The TD-DFT calculation
      successfully reproduced not only the sign but also the shape and magnitude of
      experimental CD spectrum by considering the Boltzmann-weighted average of four
      atrop-isomers. A fragment decomposition (FD) analysis of rotatory strength
      clearly revealed a noteworthy effect; the tilting motion concomitant with the
      rotating motion of the substituent affects the sign and magnitude of CD signals.
      It was found that even when the absolute structure of the chiral core moiety does
      not change, the slight motion of the substituent can trigger the inversion of the
      CD signal. 

PMID- 24437973
TI  - Fission products from the damaged Fukushima reactor observed in Hungary.
AB  - Fission products, especially (131)I, (134)Cs and (137)Cs, from the damaged
      Fukushima Dai-ichi nuclear power plant (NPP) were detected in many places
      worldwide shortly after the accident caused by natural disaster. To observe the
      spatial and temporal variation of these isotopes in Hungary, aerosol samples were
      collected at five locations from late March to early May 2011: Institute of
      Nuclear Research, Hungarian Academy of Sciences (ATOMKI, Debrecen, East Hungary),
      Paks NPP (Paks, South-Central Hungary) as well as at the vicinity of Aggtelek
      (Northeast Hungary), Tapolca (West Hungary) and Bataapati (Southwest Hungary)
      settlements. In addition to the aerosol samples, dry/wet fallout samples were
      collected at ATOMKI, and airborne elemental iodine and organic iodide samples
      were collected at Paks NPP. The peak in the activity concentration of airborne
      (131)I was observed around 30 March (1-3 mBq m(-3) both in aerosol samples and
      gaseous iodine traps) with a slow decline afterwards. Aerosol samples of several
      hundred cubic metres of air showed (134)Cs and (137)Cs in detectable amounts
      along with (131)I. The decay-corrected inventory of (131)I fallout at ATOMKI was
      2.1+/-0.1 Bq m(-2) at maximum in the observation period. Dose-rate contribution
      calculations show that the radiological impact of this event at Hungarian
      locations was of no considerable concern. 

PMID- 24437974
TI  - High serum n6 fatty acid proportion is associated with lowered LDL oxidation and
      inflammation: the Cardiovascular Risk in Young Finns Study.
AB  - The intake of polyunsaturated fatty acids (PUFAs) is generally linked with a
      reduced cardiovascular disease (CVD) risk, but an elevated n6PUFA intake, without
      simultaneous n3PUFA supply, may elevate the risk. PUFAs are suspected as being
      easily oxidized and have a potential role in lipoprotein oxidation and
      inflammation. Saturated fatty acids (SFAs) and monounsaturated fatty acids
      (MUFAs) are resistant to oxidation. However, in a Western diet, their most
      important source is red meat, a food stuff rich in heme iron which can catalyze
      oxidative reactions. Therefore, different serum fatty acid (FA) proportions (free
      + esterified) were correlated with the status of low-density lipoprotein (LDL)
      oxidation in vivo (conjugated dienes = oxLDLlipids and antibody-based oxidized
      proteins = oxLDLprot) and inflammation (serum CRP) in 2196 Finnish subjects (age:
      24-39 years) using CVD risk factor-adjusted linear regression models. High
      n6PUFA, PUFA/SFA and n6/n3 ratios, and low SFA and MUFA were all associated with
      reduced levels of oxLDLlipids, oxLDLprot, and CRP. These findings at the
      population level suggest that PUFAs are negatively and SFAs and MUFAs positively
      related with LDL oxidation and inflammation; these conclusions are in line with
      previous observations linking PUFAs, particularly n6PUFAs, with lower CVD risk,
      and SFAs with increased risk.

PMID- 24437975
TI  - Dinuclear pyridine-4-thiolate-bridged rhodium and iridium complexes as ditopic
      building blocks in molecular architecture.
AB  - A series of dinuclear pyridine-4-thiolate (4-Spy)-bridged rhodium and iridium
      compounds [M(MU-4-Spy)(diolef)]2 [diolef = 1,5-cyclooctadiene (cod), M = Rh (1),
      Ir (2); diolef = 2,5-norbornadiene (nbd), M = Rh (3)] were prepared by the
      reaction of Li(4-Spy) with the appropriate compound [M(MU-Cl)(diolef)]2 (M = Rh,
      Ir). The dinuclear compound [Rh(MU-4-Spy)(CO)(PPh3)]2 (4) was obtained by the
      reaction of [Rh(acac)(CO)(PPh3)] (acac = acetylacetonate) with 4-pySH. Compounds
      1-4 were assessed as metalloligands in self-assembly reactions with the cis
      blocked acceptors [M(cod)(NCCH3)2](BF4) [M = Rh (a), Ir (b)] and
      [M(H2O)2(dppp)](OTf)2 [M = Pd (c), Pt (d); dppp = 1,3
      bis(diphenylphosphino)propane]. The homometallic hexanuclear metallomacrocycles
      [{M2(MU-4-Spy)2(cod)2}2{M(cod)}2](BF4)2 (M = Rh [(1a)2], Ir [(2b)2]) and the
      heterometallic hexanuclear metallomacrocycles [{Rh2(MU-4
      Spy)2(cod)2}2{Ir(cod)}2](BF4)2 [(1b)2], [{Rh2(MU-4
      Spy)2(cod)2}2{M'(dppp)}2](OTf)4 (M' = Pd [(1c)2], Pt [(1d)2]), and [{Ir2(MU-4
      Spy)2(cod)2}2{M'(dppp)}2](OTf)4 (M' = Pd [(2c)2], Pt [(2d)2]) were obtained. NMR
      spectroscopy in combination with electrospray ionization mass spectrometry was
      used to elucidate the nature of the metalloligands and their respective
      supramolecular assemblies. Most of the synthesized species were found to be
      nonrigid in solution, and their fluxional behavior was studied by variable
      temperature (1)H NMR spectroscopy. An X-ray diffraction study of the assemblies
      (1a)2 and (1d)2 revealed the formation of rectangular (9.6 A * 6.6 A) hexanuclear
      metallomacrocycles with alternating dinuclear (Rh2) and mononuclear (Rh or Pt)
      corners. The hexanuclear core is supported by four pyridine-4-thiolate linkers,
      which are bonded through the thiolate moieties to the dinuclear rhodium units,
      exhibiting a bent-anti arrangement, and through the peripheral pyridinic nitrogen
      atoms to the mononuclear corners. 

PMID- 24437976
TI  - Regio- and chemoselective immobilization of proteins on gold surfaces.
AB  - Protein chips are powerful tools as analytical and diagnostic devices for
      detection of biomolecular interactions, where the proteins are covalently or
      noncovalently attached to biosensing surfaces to capture and detect target
      molecules or biomarkers. Thus, fabrication of biosensing surfaces for regio- and
      chemoselective immobilization of biomolecules is a crucial step for better
      biosensor performance. In our previous studies, a regio- and chemoselective
      immobilization strategy was demonstrated on glass surfaces. This strategy is now
      used to regioselectively attach proteins to self-assembled monolayers (SAMs) on
      gold surfaces. Recombinant green fluorescent protein (GFP), glutathione S
      transferase (GST), and antibody-binding protein G, bearing a C-terminal CVIA
      motif, were prepared and a farnesyl analogue with an omega-alkyne moiety was
      attached to the sulfhydryl moiety in the cysteine side chain by protein
      farnesyltransferase. The proteins, modified with the bioorthogonal alkyne
      functional group, were covalently and regioselectively immobilized on thiol or
      dithiocarbamate (DTC) SAMs on a gold surface by a Huigsen [3 + 2] cycloaddition
      reaction with minimal nonspecific binding. A concentration-dependent increase of
      fluorescence intensity was observed in wells treated with GFP on both thiol- and
      DTC-SAMs. The highly ordered, densely packed layer allowed for a high loading of
      immobilized protein, with a concomitant increase in substrate binding capacity.
      The DTC-SAMs were substantially more resistant to displacement of the immobilized
      proteins from the gold surface by beta-mercaptoethanol than alkane-thiol SAMs. 

PMID- 24437977
TI  - Phenolic extracts from Rhus verniciflua Stokes bark by decompressing inner
      ebullition and their antioxidant activities.
AB  - Decompressing inner ebullition (DIE) can reduce the extraction liquid boiling
      point and polyphenols oxidation in the extraction process. The aim of this study
      is to optimise the phenolic extraction process by DIE and to examine the
      antioxidant activities. The extraction process parameters were observed by
      central composite design. The antioxidant activity was measured using 1,1
      diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing power assays. The results
      showed that the optimal extraction condition is extract time of 90 min,
      temperature of 45 degrees C, solid-liquid ratio of 1:20 g/mL, vacuum degree of -
      0.08 MPa, ethanol concentration of 60%, while the phenolic content was 5.4%. The
      phenolic extracts from Rhus verniciflua Stokes bark had better antioxidant
      activities; the antioxidant activity (IC50) of the DIE was 20 MUg/mL by the DPPH
      method. The reducing power of the phenolic extracts was significantly related to
      their total phenolic content (R = 0.9903). The results presented show that the
      DIE method is an effective method for polyphenols extraction. 

PMID- 24437978
TI  - Genetic diagnosis in malignant hemopathies: from cytogenetics to next-generation
      sequencing.
AB  - Since the first specific chromosomal abnormality was identified in leukemia more
      than 50 years ago, technology has much evolved, now allowing the deciphering of
      cancer genomes in ever-greater detail. However, much has still to be learned as
      we have not yet completely dissected all the genomic aberrations driving the
      genesis and the evolution of malignant hemopathies. The first techniques that
      have been developed allowed 'gross' chromosomal abnormalities to be identified.
      They include conventional and molecular cytogenetics and microarray-based
      techniques. However, these techniques can only reveal part of the problem, as
      genes can be altered in a number of ways (mutations, methylation and so on). This
      led to the development of what is now known as next-generation sequencing (NGS).
      Each method has advantages and limits. At present, no single method can decipher
      all the mechanisms involved in leukemogenesis. Therefore, in our view, it is
      unlikely that a particular technique will become the 'gold standard'. 

PMID- 24437979
TI  - Penicillipyrones A and B, meroterpenoids from a marine-derived Penicillium sp.
      fungus.
AB  - Penicillipyrones A (1) and B (2), two novel meroterpenoids, were isolated from
      the marine-derived fungus Penicillium sp. On the basis of the results of combined
      spectroscopic analyses, these compounds were structurally elucidated to be
      sesquiterpene gamma-pyrones from a new skeletal class derived from a unique
      linkage pattern between the drimane sesquiterpene and pyrone moieties. Compound 2
      elicited significant induction of quinone reductase. 

PMID- 24437981
TI  - Medical science beyond formal institutional boundaries.

PMID- 24437980
TI  - 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone protects the impaired insulin
      secretion induced by glucotoxicity in pancreatic beta-cells.
AB  - 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated and
      purified from the dried flower buds of Cleistocalyx operculatus (Roxb.) Merr. et
      Perry (Myrtaceae), was investigated for its insulinotropic benefits against
      glucotoxicity using in vitro methods. When exposed to high glucose at the
      cytotoxicity level for 48 h, RIN-5F beta-cells experienced a significant
      viability loss and impaired insulin secretion function, whereas cotreating with
      DMC could protect beta-cells against glucotoxicity-induced decrease in glucose
      stimulated insulin secretion in a dose-dependent manner without affecting basal
      insulin secretion. It was demonstrated that DMC increased insulin secretion
      against glucotoxicity by simulating the effect of GLP-1 and enhancing the
      expression of GLP-1R, followed by activating the signal pathway of PDX-1, PRE
      INS, and GLUT2-GCK. Another mechanism was that DMC avoided the pancreatic islet
      dysfunction resulting from cellular damage by suppressing the production of
      nitric oxide (NO) by iNOS, and the expression of MCP-1. The results indicated the
      potential application of DMC in the intervention against glucotoxicity-induced
      hyperglycemia. 

PMID- 24437984
TI  - The influence of precision requirements and cognitive challenges on upper
      extremity joint reaction forces, moments and muscle force estimates during
      prolonged repetitive lifting.
AB  - Prolonged repetitive lifting is a whole-body exertion. Despite this, the roles
      and physical exposures of the upper extremities are frequently neglected. The
      influence of precision requirements and cognitive distractions on upper extremity
      responses when lifting was evaluated by quantifying several biomechanical upper
      extremity quantities. Nine participants completed four 30-min lifting tasks with
      and without simultaneous cognitive distractions and/or precision placement
      constraints. Specific metrics evaluated were joint reaction forces and moments
      (wrist, elbow and shoulder) and modelled shoulder muscle forces (38 defined
      shoulder muscle mechanical elements). The addition of a precision requirement
      increased several metrics by up to 43%, while the addition of the cognitive
      distraction task had minimal influence. Furthermore, several metrics decreased by
      up to 14% after the first 10 min of lifting, suggesting a temporal change of
      lifting strategy. PRACTITIONER SUMMARY: Lifting tasks often include precision
      placements and cognitive demands. This study shows that precision placement
      during prolonged repetitive lifting increases upper extremity forces and moments,
      while the addition of a cognitive task is benign. Furthermore, field assessments
      of repetitive lifting should include observations longer than 10 min, as adaptive
      strategies appear to be adopted.

PMID- 24437986
TI  - Primary atlantoaxial bone tumors in children: management strategies and long-term
      follow-up.
AB  - OBJECT: Atlantoaxial tumors account for a substantial proportion of primary bone
      tumors in children. Before resection, surgeons must consider the complex regional
      anatomy, the potential for neurological compromise, craniocervical instability,
      and the question of tumor resectability in a growing spine. Using current
      technology, the authors analyzed surgical cases in this light and present
      outcomes and treatment recommendations after long-term patient follow-up.
      METHODS: The authors reviewed clinical records for 23 children whose primary
      atlantoaxial bone tumors were treated from 1996 through 2010. RESULTS:
      Pathological lesions among the 23 patients were 4 aneurysmal bone cysts, 2
      osteochondromas, 5 chordomas, 4 osteoblastomas, 3 fibrous dysplasias, 4
      eosinophilic granulomas, and 1 Ewing's sarcoma. Clinical presentation consisted
      of neck pain (n = 23), headaches and occipital pain (n = 16), myelopathy (n = 8),
      and torticollis (n = 4). Selective angiography and coil embolization were
      undertaken for all patients with aneurysmal bone cysts and osteoblastomas, 2
      patients with chordomas, 1 patient with fibrous dysplasia, and 1 patient with
      Ewing's sarcoma. Primary embolization treatment of radiation-induced aneurysmal
      bone cyst of the atlas showed complete reossification. Results of CT-guided
      needle biopsy were diagnostic for 1 patient with eosinophilic granuloma and 1
      with Ewing's sarcoma. Needle biopsies performed before referral were associated
      with extreme blood loss for 1 patient and misdiagnosis for 2 patients. Surgery
      involved lateral extrapharyngeal, transoral, posterior, and posterolateral
      approaches with vertebral artery rerouting. Complete resection was possible for 9
      patients (2 with osteochondroma, 3 with fibrous dysplasia, 2 with chordoma, and 2
      with osteoblastoma). Decompression and internal fusion were performed for 3
      patients with aneurysmal bone cysts. Of the 23 patients, 7 underwent dorsal
      fusion and 4 underwent ventral fusion of the axis body. Chemotherapy was
      necessary for the patients with eosinophilic granuloma with multifocal disease
      and for the patient with Ewing's sarcoma. There was no morbidity, and there were
      no deaths. All patients with benign lesions were free of disease at the time of
      the follow-up visit (mean +/- SD follow-up 8.8 +/- 1.1 years; range 2-18 years).
      Chordomas received proton or LINAC irradiation, and as of 4-15 years of follow
      up, no recurrence has been noted. CONCLUSIONS: Because most atlantoaxial tumors
      in children are benign, an intralesional procedure could suffice. Vascular
      control and staged resection are critical. Ventral transoral fusion or lateral
      extrapharyngeal fusion has been successful. Resection with ventral fusion and
      reconstruction are essential for vertebral body collapse. Management of
      eosinophilic granulomas must be individualized and might require diagnosis
      through needle biopsy.

PMID- 24437987
TI  - Frame-based cranial reconstruction.
AB  - The authors report on the first experiences with the prototype of a surgical tool
      for cranial remodeling. The device enables the surgeon to transfer statistical
      information, represented in a model, into the disfigured bone. The model is
      derived from a currently evolving databank of normal head shapes. Ultimately, the
      databank will provide a set of standard models covering the statistical range of
      normal head shapes, thus providing the required template for any standard
      remodeling procedure as well as customized models for intended overcorrection. To
      date, this technique has been used in the surgical treatment of 14 infants (age
      range 6-12 months) with craniosynostosis. In all 14 cases, the designated
      esthetic result, embodied by the selected model, has been achieved, without
      morbidity or mortality. Frame-based reconstruction provides the required tools to
      precisely realize the surgical reproduction of the model shape. It enables the
      establishment of a self-referring system, feeding back postoperative growth
      patterns, recorded by 3D follow-up, into the model design. 

PMID- 24437988
TI  - Design hierarchical electrodes with highly conductive NiCo2S4 nanotube arrays
      grown on carbon fiber paper for high-performance pseudocapacitors.
AB  - We report on the development of highly conductive NiCo2S4 single crystalline
      nanotube arrays grown on a flexible carbon fiber paper (CFP), which can serve not
      only as a good pseudocapacitive material but also as a three-dimensional (3D)
      conductive scaffold for loading additional electroactive materials. The resulting
      pseudocapacitive electrode is found to be superior to that based on the sibling
      NiCo2O4 nanorod arrays, which are currently used in supercapacitor research due
      to the much higher electrical conductivity of NiCo2S4. A series of electroactive
      metal oxide materials, including CoxNi1-x(OH)2, MnO2, and FeOOH, were deposited
      on the NiCo2S4 nanotube arrays by facile electrodeposition and their
      pseudocapacitive properties were explored. Remarkably, the as-formed CoxNi1
      x(OH)2/NiCo2S4 nanotube array electrodes showed the highest discharge areal
      capacitance (2.86 F cm(-2) at 4 mA cm(-2)), good rate capability (still 2.41 F
      cm(-2) at 20 mA cm(-2)), and excellent cycling stability (~ 4% loss after the
      repetitive 2000 cycles at a charge-discharge current density of 10 mA cm(-2)).

PMID- 24437989
TI  - Spatiotemporal patterns of stable isotopes and hydrochemistry in springs and
      river flow of the upper Karkheh River Basin, Iran.
AB  - Karst springs of the Zagros Mountains contribute a significant amount to
      agricultural and human water demands of western and south-western Iran. For an
      adequate management of available water resources in semi-arid and arid regions,
      sufficient hydrological monitoring is needed, and hydro-chemical and isotope
      hydrological data provide important additional information. About 350 water
      samples were collected from precipitation, river water, and karst springs of the
      upper part of the Karkheh River Basin (20,895 km(2)) located between 33 degrees
      35(') and 34 degrees 55(') North and 46 degrees 22(') and 49 degrees 10(') East
      with elevations ranging from 928 to 3563 m above sea level. Sampling was
      conducted in monthly time resolution from August 2011 to July 2012. All samples
      were analysed for hydro-chemical parameters (pH, electrical conductivity, and
      major ions) and stable isotopes (deuterium, oxygen-18). Isotope values of
      precipitation indicate a local meteoric water line (Zagros MWL delta(2)H=6.8
      delta(18)O+10.1; R(2)=0.99) situated between the Mediterranean MWL and Global
      MWL. Spring and river water isotope values vary between-7.1 and-4.1 0/00, and-38
      and-25 0/00 for delta(18)O and delta(2)H, respectively, responding to winter
      snowmelt and evaporation. This work implements stable isotopes and hydro-chemical
      information of springs and river water to understand hydrological and hydro
      geological interrelations in karstic semi-arid areas and helps to improve the
      current water resources management practices of western Iran.

PMID- 24437990
TI  - Effects of a modified Hospital Elder Life Program on frailty in individuals
      undergoing major elective abdominal surgery.
AB  - OBJECTIVES: To test the effects of a modified Hospital Elder Life Program (mHELP)
      on frailty. DESIGN: Matched and unmatched analyses of data from a before-and
      after study. SETTING: Hospital, inpatient. PARTICIPANTS: Participants aged 65 and
      older (n = 189) undergoing major elective abdominal surgery at a medical center
      in Taiwan. INTERVENTION: The mHELP included three nursing interventions: early
      mobilization, oral and nutritional assistance, and orienting communication.
      MEASUREMENTS: Frailty rate and transitions between frailty states from hospital
      discharge to 3 months after discharge using Fried's phenotype criteria
      categorized as nonfrail (0 or 1 criteria present), prefrail (2 or 3 criteria
      present), and frail (4 or 5 criteria present). RESULTS: In matched pairs,
      participants who received the mHELP interventions were significantly less likely
      to be frail at discharge (19.2%) than matched controls (65.4%) (adjusted odds
      ratio (AOR) = 0.10, 95% CI = 0.02-0.39). Transitions to states of greater frailty
      during hospitalization were more common for participants in the control group.
      Three months after discharge, participants who received the mHELP intervention
      during hospitalization were less likely to be frail (17.3%) than matched controls
      (23.1%) (AOR = 0.73, 95% CI = 0.21-2.56), although this difference did not
      achieve statistical significance. CONCLUSION: The mHELP intervention is effective
      in reducing frailty by hospital discharge, but the benefit is diminished by 3
      months after discharge. Thus, the mHELP provides a useful approach to manage in
      hospital frailty for older adults undergoing major abdominal surgery.

PMID- 24437991
TI  - Proteome and allergenome of Asian wasp, Vespa affinis, venom and IgE reactivity
      of the venom components.
AB  - Vespa affinis (Asian wasp, Thai banded tiger wasp, or local name: Tor Hua Seua)
      causes the most frequent incidence of medically important Hymenoptera sting in
      South and Southeast Asia. However, data on the venom components attributable to
      the sting derived-clinical manifestations (local reactions, IgE mediated
      anaphylaxis, or systemic envenomation) are lacking. This study provides the first
      set information on V. affinis venom proteome, allergenome, and IgE reactivity of
      individual venom components. From 2DE-gel based-proteomics, the venom revealed 93
      protein spots, of which proteins in 51 spots could be identified and classified
      into three groups: typical venom components and structural and housekeeping
      proteins. Venom proteins in 32 spots reacted with serum IgE of wasp allergic
      patients. Major allergenic proteins that reacted to IgE of >50% of the wasp
      allergic patients included PLA1 (100%), arginine kinase (73%), heat shock 70 kDa
      protein (73.3%), venom allergen-5 (66.7%), enolase (66.7%), PLA1 magnifin (60%),
      glyceraldehyde-3-phosphate dehydrogenase (60%), hyaluronidase (53.3%), and
      fructose-bisphosphate aldolase (53.3%). The venom minor allergens were GB17876
      transcript (40%), GB17291 transcript (20%), malic enzyme (13.3%), aconitate
      hydratase (6.7%), and phosphoglucomutase (6.7%). The information has diagnostic
      and clinical implications for future improvement of case diagnostic sensitivity
      and specificity, component-resolve diagnosis, and design of specific Hymenoptera
      venom immunotherapy. 

PMID- 24437992
TI  - [Ocular trauma in childhood at the University Hospital Ostrava in the years 2007
      2011].
AB  - OBJECTIVE: to investigate and analyze the group of child patients with ocular
      trauma in the Ostrava region in the Czech Republic. METHODS: A retrospective
      observational case series. We reviewed and analyzed clinical records of all the
      paediatric patients with ocular trauma treated at the University Hospital Ostrava
      in the years 2007 - 2011. Age, sex, mechanism of injury, type of ocular trauma,
      the consequences of injury and period of the year when the accident occurred were
      evaluated. BETT classification used in this study was modified and extended by
      chemical and thermal injuries and orbital trauma. Ocular burns, including thermal
      and chemical burns, were graded using the classification for ocular surface burns
      by Dua. RESULTS: 448 children (309 boys, 139 girls), aged from 3 months to 17
      years (median 10 years) were included in this study. The most common ocular
      injury was closed globe injury (253 patients, 56,5 %), the next common were
      orbital injuries (149 patients, 33,3 %), burns injuries (39 patients, 8,7 %), the
      least frequent were open globe injuries (7 patients, 1,6 %). The most common
      mechanism of ocular trauma was hit by object (34,6 %), followed by trauma caused
      by blows and falls (15,2 %) and hit by another person (10,3 %). The 50,9 % of
      injuries occurred in days of school attendance. 10,3 % of injuries occurred
      directly at the school or preschool facilities. 6,5 % of the injuries were
      polytraumas, which required interdisciplinary cooperation. CONCLUSION: This study
      demonstrated that the incidence of eye injuries is greater in boys, mainly
      adolescents. Closed globe injuries are the predominant type of ocular trauma in
      childhood. The mechanism of ocular trauma is variable. Nonetheless there is a
      relation between the mechanism and the age of the child. Further research in
      terms of how the preventive measures would affect the incidence and severity of
      ocular trauma in children would be beneficial. The modified BETT classification
      of ocular trauma, including chemical and thermal injuries and orbital trauma may
      better address current requirements.

PMID- 24437993
TI  - [Anterior uveitis caused by electrical discharge in whole body injuries (fifteen
      years study)].
AB  - AIM: To inform about clinical analysis of early ophthalmologic complication
      (uveitis) in patients sustained electric discharge injury. STUDY GROUP: The
      authors refer about fifteen years follow-up of pediatric patients at the
      Department of Burns Medicine, 3rd Medical Faculty, Charles University in Prague,
      Czech Republic, E.U., with electric discharge injury, in which the anterior
      uveitis was detected. Out of 43 patients after electric discharge injury, the
      always-unilateral iritis (iridocyclitis) was diagnosed in four (9 %) patients
      according to thorough going follow-up after first accidental diagnosis in the
      year 1998. Out of four boys aged 12 - 15 years, the first two were injured during
      the "play" - due to the contact with electrical trolley wire while running on
      railroad wagons roofs, and the two others were stuck by lighting under a tree by
      secondary electrical discharge. More serious skin burns were noticed in high
      voltage current injury - 69 % or 55 % of body surface respectively, with the
      necessity of skin transplantation. The same was necessary in one boy injured by
      lighting with burns of 25 % of body surface, while the last one had on the skin
      the lighting signs only. In most of the patients, the resuscitation care due to
      unconsciousness and posttraumatic shock was necessary. The anterior uveitis was
      diagnosed subsequently, after initial preliminary diagnoses as conjunctivitis,
      episcleritis, or ophthalmia electrical. The iritis without visual function
      decrease was discovered in few days after the injury in three patients. Treatment
      and results: The inflammation was in these cases treated with short-term
      application of mydriatic and corticosteroid eye drops. Once only, the uveitis
      appeared after two months during the patients hospitalization and then the signs
      of iridocyclitis in the anterior chamber worsened and caused visual acuity
      decrease to hand movement in front of the eye. The condition was successfully
      treated by means of parabulbar betamethasone injection and long-term application
      of mydriatic and corticosteroid drops. CONCLUSION: Uveitis in electrical
      discharge injury of different origin is a rare early complication, which may be
      determined solely by regular ophthalmologic follow-up examinations of the
      patients.

PMID- 24437994
TI  - [Anatomical results of cryosurgical procedures in rhegmatogenous retinal
      detachment - our experience].
AB  - AIM: To evaluate retrospectively anatomical results of cryosurgical treatment of
      non-complicated idiopathic rhegmatogenous retinal detachment. To assess the
      successfulness of primary cryosurgical surgeries, permanent retinal re
      attachment; to review the efficacy of cryosurgical procedures according to chosen
      surgical technique and patients age as well. MATERIAL AND METHODS: In the
      evaluated group were included 120 eyes of 120 patients operated on in the years
      2003- 2012 at the Department of Ophthalmology, Faculty Hospital and School of
      Medicine, Palacky University, Olomouc, Czech Republic, E.U. All of the patients
      were phakic. The patients were evaluated at one and three months after the
      surgery. The posterior pole examinations were done by means of biomicroscopic
      examination and indirect ophthalmoscopy. The retina was evaluated as attached in
      whole extent in case of re-established contact between the neurosensory retina
      and the retinal pigment epithelium in the whole periphery. RESULTS: In 106 (88 %)
      patients, the re-attachment of the retina was achieved by solely cryosurgical
      procedure; in 117 (97.5 %) patients, the definite re-attachment of the retina was
      achieved. In three patients (2.5 %), the retina remained detached. Statistically
      better results were obtained in patients with peroperative exodrainage of the
      subretinal fluid and in patients younger than 50 years of age. CONCLUSION: We
      established the usefulness of cryosurgical operative procedure in treatment of
      uncomplicated idiopathic rhegmatogenous retinal detachment in phakic patients.
      Especially in young phakic patients, the cryosurgical procedure may be protective
      to preserve the clear lens and eye accommodation.

PMID- 24437995
TI  - [Analysis of reasons of intraocular lenses explantation].
AB  - AIM: To analyze the reasons of intraocular lenses (IOL) explantation. METHODS:
      Retrospective study of 22 eyes of 21 patients. Those patients underwent
      explantation of intraocular lenses between the years 2008 to 2011. The study
      group included two eye groups. Group A included eyes with explanted monofocal IOL
      (14 eyes of 13 patients) and group B included eyes with explanted multifocal IOL
      (8 eyes of 7 patients). Reasons requiring explantation were analyzed based on
      subjective patient complaints and on objective ocular findings in health
      documentation as well. RESULTS: The most common indications of explantation in
      Group A of monofocal lenses were incorrect IOL power, followed by IOL luxation,
      decentration and IOL opacity. In Group B of multifocal IOL, the most common
      reasons for IOL removing were halo and glare, inadequate postoperative
      expectations and incorrect IOL power. CONCLUSION: The main reason for IOL
      exchange in Group A of monofocal lenses was the incorrect power, while in Group B
      of multifocal IOL the main reason were the disturbing photic phenomenon like
      glare and halo. Careful patient selection, good surgical technique, optimally
      selected IOL power measurements based on precise biometry readings as well high
      quality of IOL materials are the most important factors in minimizing the risk
      for IOL explantation.

PMID- 24437996
TI  - [Contemporary possibilities of intraocular pressure measurement].
AB  - Authors introduced current possibilities of measuring intraocular pressure (IOP).
      A list of available methods of monitoring IOP is published; contact measurement
      method IOP directly on the cornea, but also over upper lid, methodology of
      minimal contact and non-contact measurement. Following contact methods are
      described; former measurements of IOP by impression Schiotz tonometer and the
      current methodology applanation. So far as the gold standard measurement Goldmann
      applanation tonometer (GAT) is considered, another methodology with applanation
      measurements are compared: Pascal dynamic contoured tonometer (DCT ),
      BioResonator - resonant applanation tonometer (ART ), digital applanation
      tonometer Tonopen and last hit: continuous measurement of IOP by Sensimed
      Triggerfish. Orientation and rapid assessment is palpation pressure control over
      the lid and measuring by tonometer Diaton. Rebound tonometer (RBT) iCare belongs
      to measurements with minimal contact, no need anesthetic drops and fluorescein,
      therefore a self - home version of IOP measurements (Icare ONE) is developed. Non
      contact measurement of IOP by different pneumotonometers is popular for screening
      assessment of IOP. Reichert Ocular Response Analyzer (ORA) is a non-contact
      applanation IOP measurement and reveals additional properties of the cornea. In
      the discussion of a range methodology is evaluated, the experience of other
      authors and their own experience is compared. For monitoring of patients is
      necessary to select the most suitable methodology, measure repeatedly and
      accurately to allow long-term monitoring of intraocular pressure.

PMID- 24437997
TI  - High nuclearity (octa-, dodeca-, and pentadecanuclear) metal (M = Co(II), Ni(II))
      phosphonate cages: synthesis, structure, and magnetic behavior.
AB  - The synthesis, structural characterization, and magnetic property studies of five
      new transition metal (M = Co, Ni) phosphonate-based cages are reported. Three
      substituted phenyl and benzyl phosphonate ligands [RPO3H2; R1 = p-tert
      butylbenzyl, R2 = p-tert-butylphenyl, R3 = 3-chlorobenzyl] were synthesized and
      employed to seek out high-nuclearity cages. Complexes 1-3 are quasi-isostructural
      and feature a dodecanuclear metal-oxo core having the general molecular formula
      of [M12(MU3-OH)4 (O3PR)4(O2C(t)Bu)6 (HO2C(t)Bu)6(HCO3)6] {M = Co, Ni and R = R1
      for 1 (Co12), R2 for 2, 3 (Co12, Ni12)}. The twelve metal centers are arranged at
      the vertices of a truncated tetrahedron in a manner similar to Keggin ion.
      Complex 4 is an octanuclear nickel phosphonate cage [Ni8(MU3-OH)4 (OMe)2(O3PR1)2
      (O2C(t)Bu)6(HO2C(t)Bu)8], and complex 5 represents a pentadecanuclear cobalt
      phosphonate cage, [Co15(chp)8(chpH) (O3PR3)8(O2C(t)Bu)6], where chpH = 6-chloro-2
      hydroxypyridine. Structural investigation reveals some interesting geometrical
      features in the molecular cores, which may provide new models in single molecular
      magnetic materials. Magnetic property measurements of compounds 1-5 indicate the
      coexistence of both antiferromagnetic and ferromagnetic interactions between
      magnetic centers for all cages. 

PMID- 24437998
TI  - Identification and quantitative analysis of polyphenolic compounds from the
      indigo plant (Polygonum tinctorium Lour).
AB  - The indigo plant (Polygonum tinctorium Lour) has been used traditionally as a
      medicinal plant with a variety of biological effects. Of these, polyphenolic
      ingredients are postulated to contribute to these activities. However, the
      identification and quantification of polyphenolic compounds in indigo plants have
      not been conducted comprehensively until now. This study was undertaken to
      identify the related ingredients by combined instrumental analyses using ultra
      performance liquid chromatography electrospray-ionisation mass spectrometry and
      gas chromatography-mass spectrometry after the extracts of plant tissues were
      fractionated by absorption column chromatography. These analyses allowed the
      identification of kaempferol, quercetin-3-O-glucuronide, quercetin, kaempferol-3
      O-glucopyranoside, caffeic acid, chlorogenic acid and tentative 3,5,4'-trihydroxy
      6,7-methylenedioxyflavone. Furthermore, predominant polyphenolic compounds were
      quantified by reverse-phase high-performance liquid chromatography and capillary
      gas chromatography, revealing the higher proportions of kaempferol, quercetin-3-O
      glucuronide and quercetin among them. The results indicate that the indigo plant
      is a promising source for flavonoids and the related compounds with beneficial
      medicinal effects. 

PMID- 24438000
TI  - One photon yields two isomerizations: large atomic displacements during
      electronic excited-state dynamics in ruthenium sulfoxide complexes.
AB  - Photochromic compounds efficiently transduce photonic energy to potential energy
      for excited-state bond-breaking and bond-forming reactions. A critical feature of
      this reaction is the nature of the electronic excited-state potential energy
      surface and how this surface facilitates large nuclear displacements and
      rearrangements. We have prepared two photochromic ruthenium sulfoxide complexes
      that feature two isomerization reactions following absorption of a single photon.
      We show by femtosecond transient absorption spectroscopy that this reaction is
      complete within a few hundred picoseconds and suggest that isomerization occurs
      along a conical intersection seam formed by the ground-state and excited-state
      potential energy surfaces. 

PMID- 24437999
TI  - Cyanohydrin phosphonate natural product from Streptomyces regensis.
AB  - Streptomyces regensis strain WC-3744 was identified as a potential phosphonic
      acid producer in a large-scale screen of microorganisms for the presence of the
      pepM gene, which encodes the key phosphonate biosynthetic enzyme
      phosphoenolpyruvate phosphonomutase. (31)P NMR revealed the presence of several
      unidentified phosphonates in spent medium after growth of S. regensis. These
      compounds were purified and structurally characterized via extensive 1D and 2D
      NMR spectroscopic and mass spectrometric analyses. Three new phosphonic acid
      metabolites, whose structures were confirmed by comparison to chemically
      synthesized standards, were observed: (2-acetamidoethyl)phosphonic acid (1), (2
      acetamido-1-hydroxyethyl)phosphonic (3), and a novel cyanohydrin-containing
      phosphonate, (cyano(hydroxy)methyl)phosphonic acid (4). The gene cluster
      responsible for synthesis of these molecules was also identified from the draft
      genome sequence of S. regensis, laying the groundwork for future investigations
      into the metabolic pathway leading to this unusual natural product. 

PMID- 24438003
TI  - Neonatal cerebral morphometry and later risk of persistent
      inattention/hyperactivity in children born very preterm.
AB  - BACKGROUND: Attention problems are among the most prevalent neurobehavioral
      morbidities affecting very preterm (VPT) born children. The first study aim was
      to document rates of persistent attention/hyperactivity problems from ages 4 to 9
      years in a regional cohort of VPT born children. The second aim was to examine
      the extent to which persistent problems were related to cerebral white matter
      abnormality and structural development on neonatal MRI. METHODS: Data were drawn
      from a prospective longitudinal study of 110 VPT (<=32 weeks gestation) and 113
      full-term (FT) children born from 1998 to 2000. At term equivalent, all VPT and
      10 FT children underwent cerebral structural MRI, with scans analyzed
      qualitatively for white matter abnormalities and quantitatively for cortical and
      subcortical gray matter, myelinated and unmyelinated white matter, and
      cerebrospinal fluid volumes. At ages 4, 6, and 9 years, each child's parent and
      teacher completed the Inattention/Hyperactivity subscale of the Strengths and
      Difficulties Questionnaire. RESULTS: VPT born children had a fivefold increased
      risk of persistent attention/hyperactivity problems compared with FT children
      (13.1% vs. 2.8%; p = .002). No association was found between neonatal white
      matter abnormalities and later persistent inattention/hyperactivity risk (p >=
      .24). In contrast, measures of cerebral structural development including
      volumetric estimates of total cerebral tissue and cerebrospinal fluid relative to
      intracranial volume were associated with an increased risk of persistent
      attention/hyperactivity problems in VPT born children (p = .001). The dorsal
      prefrontal region showed the largest volumetric reduction (?3.2-8.2 mL). These
      brain-behavior associations persisted and in some cases, strengthened after
      covariate adjustment for postmenstrual age at MRI, gender, and family
      socioeconomic status. CONCLUSIONS: Just over one in 10 VPT born children are
      subject to early onset and persistent attention/hyperactivity problems during
      childhood. These problems appear to reflect, at least in part, neonatal
      disturbances in cerebral growth and development rather than the effects of white
      matter injury.

PMID- 24438004
TI  - Measurement and computer modeling of temporary arrangements of polygonal actin
      structures in trabecular meshwork cells which consist of cross-linked actin
      networks and polygonal actin arrangements.
AB  - PURPOSE: In trabecular meshwork (TM) cells, actin geodesic arrangements were
      measured and then subjected to computational modeling to appreciate the response
      of different dome shapes to mechanical force. METHODS: Polygonal actin
      arrangements (PAAs) and cross-linked actin networks (CLANs) were induced and
      imaged by Alexa Flour((r)) 488 Phalloidin in bovine TM and human TM cells. Masked
      images were examined for size, circularity, and spoke and hub dimensions using
      ImageJ. Finite element modeling was used to create idealized dome structures and
      "realistic" PAA and CLAN models. The models were subjected to different loads
      simulating concentrated force and distortion measured. RESULTS: We provide
      evidence that PAAs and CLANs are not identical. Both structures formed flattened
      domes but PAAs were 6 times larger than CLANs, significantly more circular and
      had greater height. The dimensions of the triangulations of hubs and spokes were,
      however, remarkably similar. Hubs were around 2 MUm(2) in area, whereas spokes
      were about 5 MUm in length. Our modeling showed that temporary arrangements of
      polygonal actin structures (TAPAS) were because of their flattened shape, more
      resistant to shearing than compression when compared with idealized domes. CLANs
      were marginally more resistant to shearing than PAAs but because of size much
      more resistant to compression. CONCLUSIONS: Evidence is provided that there are 2
      types of actin icosahedrons in cultured TM cells we collectively call TAPAS.
      Modeling suggests that TAPAS have rigidity and are better at dealing with
      shearing than compression forces. The 2 types of TAPAS, PAAs, and CLANs, have
      much in common but there are size and mechanical response differences that need
      to be taken into account in future experimentation.

PMID- 24438006
TI  - Microbiota regulation of inflammatory bowel disease.
AB  - The intestines harbor over trillions of commensal bacteria, which co-evolve and
      form a mutualistic relationship with the host, with microbial-host interaction
      shaping immune adaption and bacterial communities. The intestinal microbiota not
      only benefits the host and contributes to the maintenance of intestinal
      homeostasis, but also causes chronic intestinal inflammation under certain
      conditions. Thus, understanding the microbiota regulation of inflammatory bowel
      disease (IBD) will provide great insights into the pathogenesis of IBD as well as
      potential therapeutics for IBD patients. 

PMID- 24438005
TI  - Mammalian SIRT2 inhibits keratin 19 expression and is a tumor suppressor in skin.
AB  - SIRT2 is a member of the mammalian sirtuin family (SIRT1-7). As compared with
      other sirtuins, SIRT2 is found primarily in the cytoplasm. It regulates multiple
      physiological processes. However, the precise role of SIRT2 in skin cancer
      remains unclear. Here, we show that SIRT2 is downregulated in human skin cancer
      as compared with normal skin. SIRT2 deletion increases tumor growth in mice.
      SIRT2 knockdown upregulates the stem cell marker Keratin 19 (K19) in
      keratinocytes. In mice, SIRT2 deletion up-regulates K19 and K15 while it down
      regulates the differentiation marker Loricrin in both normal skin and tumors. In
      skin tumors but not normal skin, SIRT2 deletion up-regulates the stem cell marker
      CD34 and increases the number of Ki67-positive cells. These findings indicate
      that SIRT2 is a tumor suppressor in the skin. Our findings add new insights into
      the role of SIRT2 in the molecular pathogenesis of skin cancer. 

PMID- 24438007
TI  - Traumatic intracranial injury in intoxicated patients with minor head trauma.

PMID- 24438012
TI  - Emergence of cutaneous leishmaniasis in Polonnaruwa, Sri Lanka 2008-2011.
AB  - OBJECTIVE: To report cutaneous leishmaniasis (CL) in Polonnaruwa, Sri Lanka.
      METHODS: The study population included all patients with CL reported from
      Polonnaruwa district from January 2008 through April 2012. Data were collected in
      the dermatology unit of Polonnaruwa General Hospital and the regional
      epidemiology unit of Polonnaruwa. RESULTS: Four hundred and forty six patients
      with leishmaniasis were detected; clinical details were available for 362. Mean
      annual incidence of leishmaniasis between 2008 and 2012 in Polonnaruwa district
      was 26.2 per 100,000. The case incidence steadily increased during the study
      period. Case distribution by month peaked between August and November. Cases were
      geographically clustered in three administrative divisions with a mean annual
      incidence ranging from 94.7 to 54.1 per 100,000 population. Significantly more (n
      = 294, 65.9%) males than females were affected (chi(2) for goodness of fit =
      48.4, P < 0.001). The commonest type of lesion was nodules (n = 157, 43.4%)
      followed by crust (n = 116, 32.0%). The majority of patients had lesions on upper
      limbs (n = 144, 39.8%) or the face (n = 117, 32.3%). CONCLUSION: Cutaneous
      leishmaniasis is increasing in Polonnaruwa, with clear spatial and temporal
      clustering. Sri Lanka needs more vigilant leishmaniasis surveillance.

PMID- 24438008
TI  - Use of tissue plasminogen activator in catheters used for extracorporeal renal
      replacement therapy.
AB  - BACKGROUND: Intraluminal thrombosis of central venous catheters used for renal
      replacement therapy (RRT) decreases the ability to provide adequate treatment.
      Alteplase is a recombinant tissue plasminogen activator that has been used to
      improve the function of catheters used for RRT in humans. OBJECTIVES: To
      retrospectively review alteplase instillation in dysfunctional catheters used for
      RRT in dogs and cats. ANIMALS: Seventeen dogs and 8 cats receiving RRT for kidney
      failure. METHODS: Medical records of patients in which alteplase was used for RRT
      catheter dysfunction from 2004 to 2012 were retrospectively reviewed to
      characterize reasons for use, improvement in function, increase in blood flow,
      and duration of improvement. RESULTS: Alteplase was instilled 43 times in 29
      catheters, most commonly because of suspicion that the catheter would not provide
      sufficient flow on the next treatment (n = 21). The second most common reason was
      inability to start a dialysis treatment (n = 12). Catheter function improved
      after alteplase instillation in 34 of 43 treatments (79%). Median blood flow rate
      increased by 13% (18 mL/min) in the dialysis session after alteplase
      instillation. Seven of 29 catheters (24%) were treated with alteplase on >1
      occasion (median time to second treatment, 8 days), and 1 catheter had to be
      replaced because of intractable dysfunction. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Alteplase is effective at improving function of central venous catheters used to
      provide RRT, but the results are short-lived.

PMID- 24438013
TI  - Simultaneous determination of six constituents in the fruit of Acanthopanax
      sessiliflorus (Rupr. et Maxim.) Seem. by HPLC-UV.
AB  - A simple and accurate liquid chromatographic method was developed for the
      simultaneous determination of six constituents in the fruit of Acanthopanax
      sessiliflorus. The conditions of sample extraction were optimised by using
      orthogonal design. The method provided good accuracy with recoveries in the range
      of 95.6-101.6% and good precision with RSD values less than 3.0%, which has been
      successfully applied to the quantitative determination of the six compounds in
      the fruit of A. sessiliflorus from two maturation periods. 

PMID- 24438014
TI  - Isotope effects in the enzymatic oxidation of tryptamine to 3-indolyl
      acetaldehyde.
AB  - The reaction mechanisms of the enzymatic deamination of tryptamine catalysed by
      the enzyme monoamine oxidase (MAO, EC 1.4.3.4) were investigated using the
      kinetic isotope effect and solvent isotope effect methods. The numerical values
      of these deuterium effects in the (1S) and (1R) positions of tryptamine were
      determined using the non-competitive spectrophotometry. The deuterium-labelled
      isotopologue [(1S)-(2)H]tryptamine was obtained in two steps by enzymatic
      coupling of indole with S-methyl-l-cysteine in a deuterated medium followed by
      enzymatic decarboxylation of the resulting [2-(2)H]-l-tryptophan. [(1R)
      (2)H]tryptamine was obtained by enzymatic decarboxylation of l-tryptophan in the
      fully deuterated medium. 

PMID- 24438015
TI  - Atmospheric chemical reactions of monoethanolamine initiated by OH radical:
      mechanistic and kinetic study.
AB  - Monoethanolamine (MEA) is a benchmark and widely utilized solvent in amine-based
      postcombustion CO2 capture (PCCC), a leading technology for reducing CO2 emission
      from fossil fuel power plants. The large-scale implementation of PCCC would lead
      to inevitable discharges of amines to the atmosphere. Therefore, understanding
      the kinetics and mechanisms of the transformation of representative amine MEA in
      the atmosphere is of great significance for risk assessment of the amine-based
      PCCC. In this study, the H-abstraction reaction of MEA with .OH, and ensuing
      reactions of produced MEA-radicals, including isomerization, dissociation, and
      bimolecular reaction MEA-radicals+O2, were investigated by quantum chemical
      calculation [M06-2X/aug-cc-pVTZ//M06-2X/6-311++G(d,p)] and kinetic modeling. The
      calculated overall rate constant [(7.27 * 10(-11)) cm(3) molecule(-1) s(-1)] for
      H-abstraction is in excellent agreement with the experimental value [(7.02 +/-
      0.46) * 10(-11) cm(3) molecule(-1) s(-1)]. The results show that the product
      branching ratio of NH2CH2 . CHOH (MEA-beta) (43%) is higher than that of NH2 .
      CHCH2OH (MEA-alpha) (39%), clarifying that MEA-alpha is not an exclusive product.
      On the basis of the unveiled reaction mechanisms of MEA-radicals + O2, the proton
      transfer reaction mass spectrometry signal (m/z 60.044), not recognized in the
      experiment, was identified.

PMID- 24438016
TI  - Outlook for a dengue vaccine.
AB  - Dengue is an increasing medical problem in subtropical and tropical countries.
      The search for a safe and effective vaccine is complicated by the fact that there
      are four types of dengue virus and that, if a vaccine is live attenuated, it
      should be proven not to cause the life-threatening form of dengue, dengue
      haemorrhagic fever. So far one vaccine candidate, a four-valent chimeric vaccine
      constructed from a yellow fever vaccine strain, has reached large clinical trials
      and has been shown to offer protection against dengue types 1, 3 and 54 but not
      against dengue type 2. It is highly likely that an effective vaccine will be
      available in the next decade. 

PMID- 24438017
TI  - Posterior retroperitoneoscopic adrenalectomy: outcomes and lessons learned from
      initial 50 cases.
AB  - BACKGROUND: Posterior retroperitoneoscopic adrenalectomy (PRA) is an alternative
      approach to minimally invasive adrenalectomy, potentially offering less pain and
      faster recovery compared with laparoscopic transperitoneal adrenalectomy (LA).
      The authors have recently changed from LA to PRA in suitable patients and audited
      their first 50 cases. METHODS: Data were prospectively collected for 50
      consecutive PRAs performed by the same surgeon. Patient demographics, tumour
      characteristics, analgesia use, operative and preparation time, length of stay,
      and complications were recorded. RESULTS: Fifty adrenalectomies were performed in
      49 patients. The median (range) age was 58.5 years (30-83) and the majority of
      patients were female (n = 33, 66.0%). The median (interquartile range (IQR))
      preparation time was 35.5 (28.5-50.0) and median operation time was 70.5 (54-85)
      min, which decreased during the study period. After a learning curve of 15 cases,
      median operative time reached 61 min. PRA patients required minimal post
      operative analgesia, with a median (IQR) of 0 (0-5) mg of intravenous morphine
      equivalent used. The median (IQR) length of stay was 1 (1-1) day, with 8 (16.0%)
      same-day discharges. There were four complications: one blood pressure lability
      from a phaeochromocytoma, one reintubation, one self-limited bleed and one
      temporary subcostal neuropraxia. There were no conversions to open surgery or
      deaths. CONCLUSION: Our results support previously published findings that PRA is
      a safe procedure, with a relatively short learning curve, resulting in minimal
      post-operative analgesia use and short length of hospital stay.

PMID- 24438019
TI  - Immunohistochemical expression of homeoproteins Six1 and Pax3 in breast phyllodes
      tumours correlates with histological grade and clinical outcome.
AB  - AIMS: Homeoproteins are transcription factors which critically regulate
      developmental processes. Deregulated expression of homeoproteins is observed in
      several malignancies, such as breast cancer and rhabdomyosarcoma, and contributes
      to malignant progression. We aimed to investigate the expression and prognostic
      importance of Six1 and Pax3 homeoproteins in phyllodes tumours - a group of
      uncommon biphasic tumours comprising both epithelial and stromal components.
      METHODS AND RESULTS: A total of 272 cases diagnosed from January 2003 to December
      2010 were included in this study - 189 (69.5%) benign, 60 (22.1%) borderline and
      23 (8.4%) malignant tumours. Immunohistochemistry was performed on tissue
      microarray sections using antibodies against Six1 and Pax3. Staining H-score was
      assessed in epithelium and stroma separately, and correlated with tumour grade,
      clinicopathological parameters and prognosis. Tumour grade was associated
      positively with stromal cytoplasmic expression (P < 0.001; P = 0.011) but
      correlated negatively with epithelial nuclear expression (P = 0.013; P = 0.007)
      of both Six1 and Pax3. High stromal cytoplasmic expression of Six1 was associated
      with metastasis (P = 0.044) and shorter time to recurrence (P = 0.056). Pax3
      stromal cytoplasmic expression was associated with poorer overall survival (P =
      0.033). CONCLUSIONS: Six1 and Pax3 expression is correlated with tumour grade,
      unfavourable clinicopathological parameters and poorer clinical outcome,
      suggesting that both proteins may play a role in malignant progression.

PMID- 24438020
TI  - Difference in muscle quality over the adult life span and biological correlates
      in the Baltimore Longitudinal Study of Aging.
AB  - OBJECTIVES: To examine differences in a proxy measure of muscle quality across
      the adult life span and explore potential mechanisms of muscle quality change
      through identification of cross-sectional correlates of muscle quality. DESIGN:
      Cross-sectional study. SETTING: Baltimore Longitudinal Study of Aging.
      PARTICIPANTS: Seven hundred eighty-six individuals with a mean age of 66.3 (range
      26-96) (N = 786). A sensitivity analysis was conducted in a subset of
      participants matched according to sex, muscle mass, and body size. MEASUREMENTS:
      Muscle quality was operationalized as the ratio of knee-extension strength
      (isokinetic dynamometry) to thigh muscle cross-sectional area (computed
      tomography). Differences in muscle strength, muscle area, and muscle quality
      ratio with age were evaluated, and the association between the muscle quality
      ratio and measures reflecting domains of cognitive function, motor control,
      peripheral nerve function, adiposity, glucose homeostasis, and inflammation were
      assessed through multivariate regression analyses. RESULTS: A linear relationship
      between age and muscle quality ratio was observed, suggesting a gradual decline
      in muscle quality over the adult life course. Associations were observed between
      muscle quality ratio and measures of adiposity, as well as peroneal nerve motor
      conduction velocity, finger tapping speed, and memory performance (P < .01). The
      association between muscle quality ratio and nerve conduction velocity was
      maintained after adjustment for anthropometric measurements (P < .05).
      CONCLUSION: Muscle quality declines progressively with age over the adult life
      span and is affected by obesity and neurological factors. Studies are needed to
      clarify the mechanisms of these associations and their implications for
      functional outcomes.

PMID- 24438021
TI  - Preparation and evaluation of periodontal films based on polyelectrolyte complex
      formation.
AB  - Local intra-pocket drug delivery devices can provide an effective concentration
      of the antimicrobial agent at the site of action with avoidance of undesirable
      side effects. This study explored the application of chitosan-alginate and
      chitosan-pectin polyelectrolyte complex (PEC) films as drug release regulators
      for tetracycline HCl (Tc) to treat periodontal pockets. Periodontal films with
      1:1 Tc:PEC ratio were prepared using 1:1 chitosan (Ch) to sodium alginate (A) or
      1:3 Ch to pectin (P). The scanning electron microscope showed acceptable film
      appearance and differential scanning calorimetry analysis confirmed complex
      formation. The in vitro release studies for both films showed a burst drug
      release, followed by prolonged release for 70 h. A prolonged antibacterial
      activity of both films against Staphylococcus aureus ATCC 6538 was observed over
      a period of 21 days. Aging studies indicated that the five months storage period
      in freezer did not significantly influence the drug release profile or the
      antibacterial activity of both films. Clinical evaluation showed a significant
      reduction in pocket depth (p < 0.0001) to their normal values (<=3 mm). PEC films
      could be exploited as a prolonged drug release devices for treatment of
      periodontal pockets. 

PMID- 24438022
TI  - Excretory nitrogen metabolism and defence against ammonia toxicity in air
      breathing fishes.
AB  - With the development of air-breathing capabilities, some fishes can emerge from
      water, make excursions onto land or even burrow into mud during droughts. Air
      breathing fishes have modified gill morphology and morphometry and accessory
      breathing organs, which would tend to reduce branchial ammonia excretion. As
      ammonia is toxic, air-breathing fishes, especially amphibious ones, are equipped
      with various strategies to ameliorate ammonia toxicity during emersion or ammonia
      exposure. These strategies can be categorized into (1) enhancement of ammonia
      excretion and reduction of ammonia entry, (2) conversion of ammonia to a less
      toxic product for accumulation and subsequent excretion, (3) reduction of ammonia
      production and avoidance of ammonia accumulation and (4) tolerance of ammonia at
      cellular and tissue levels. Active ammonia excretion, operating in conjunction
      with lowering of ambient pH and reduction in branchial and cutaneous NH3
      permeability, is theoretically the most effective strategy to maintain low
      internal ammonia concentrations. NH3 volatilization involves the alkalization of
      certain epithelial surfaces and requires mechanisms to prevent NH3 back flux.
      Urea synthesis is an energy-intensive process and hence uncommon among air
      breathing teleosts. Aestivating African lungfishes detoxify ammonia to urea and
      the accumulated urea is excreted following arousal. Reduction in ammonia
      production is achieved in some air-breathing fishes through suppression of amino
      acid catabolism and proteolysis, or through partial amino acid catabolism leading
      to alanine formation. Others can slow down ammonia accumulation through increased
      glutamine synthesis in the liver and muscle. Yet, some others develop high
      tolerance of ammonia at cellular and tissue levels, including tissues in the
      brain. In summary, the responses of air-breathing fishes to ameliorate ammonia
      toxicity are many and varied, determined by the behaviour of the species and the
      nature of the environment in which it lives.

PMID- 24438023
TI  - Traumatic intracranial injury in intoxicated patients with minor head trauma.

PMID- 24438025
TI  - Involvement of caspase 8 and c-FLIPL in the proangiogenic effects of the tumour
      necrosis factor-related apoptosis-inducing ligand (TRAIL).
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine of
      the tumour necrosis factor superfamily, is a potent cell-apoptosis inducer,
      although its effects vary as a function of concentration. In fact, low
      concentrations of TRAIL are associated with non-apoptotic effects, such as cell
      proliferation. Here, the effects of TRAIL at different concentrations have been
      evaluated on mitogenesis and migration on human umbilical vein endothelial cells
      (HUVEC) in vitro, as well as in the chick embryo chorioallantoic membrane (CAM)
      angiogenesis model in vivo. At low concentrations, TRAIL promoted either
      mitogenesis or migration of HUVEC, evaluated using the wound healing method.
      Cleavage of caspase 8 was evaluated along with expression of the caspase 8-like
      molecule, cellular FLICE-inhibitory protein (long form) (c-FLIPL ). Low
      concentrations of TRAIL failed to induce caspase 8 processing, whereas high
      concentrations induced apoptosis of HUVEC and activation of caspase 8. Moreover,
      TRAIL induced a significant angiogenic response in the CAM assay in vivo,
      comparable with that of vascular endothelial growth factor. These data suggest
      that the non-apoptotic effects of TRAIL include mitogenesis and increased
      mobility of endothelial cells, and eventually angiogenesis. In addition, the
      results demonstrate that the c-FLIPL level is also modulated by differences in
      TRAIL concentration, suggesting its involvement in the divergent effects of
      TRAIL. In conclusion, this study envisions a proangiogenic role of TRAIL,
      suggesting that TRAIL may represent a target for pharmacological manipulation.

PMID- 24438024
TI  - Epilepsy in cats: theory and practice.
AB  - The veterinary literature on epilepsy in cats is less extensive than that for
      dogs. The present review summarizes the most important human definitions related
      to epilepsy and discusses the difficulties in applying them in daily veterinary
      practice. Epileptic seizures can have a wide range of clinical signs and are not
      necessarily typical in all cases. Whether a seizure event is epileptic can only
      be suspected based on clinical, laboratory, and neuroimaging findings as
      electroencephalography diagnostic techniques have not yet been developed to a
      sufficiently accurate level in veterinary medicine. In addition, the present
      review aims to describe other diagnoses and nonepileptic conditions that might be
      mistaken for epileptic seizures. Seizures associated with hippocampal lesions are
      described and discussed extensively, as they seem to be a special entity only
      recognized in the past few years. Furthermore, we focus on clinical work-up and
      on treatment that can be recommended based on the literature and summarize the
      limited data available relating to the outcome. Critical commentary is provided
      as most studies are based on very weak evidence. 

PMID- 24438026
TI  - Nuclear envelope localization of Ran-binding protein 2 and Ran-GTPase-activating
      protein 1 in psoriatic epidermal keratinocytes.
AB  - The nuclear localization signal (NLS)-containing proteins LEDGF and STAT3
      localize to the nucleus in both the spinous and basal layers of the epidermis in
      psoriatic skin, where they function as transcription factors or co-factors to
      activate epidermal keratinocytes (KCs). However, the mechanism underlying the
      localization of these proteins remains to be elucidated. We investigated the
      differential nucleocytoplasmic transport of NLS-containing proteins as a
      potential pathogenic mechanism for psoriasis vulgaris. Nucleoporins play an
      important role in the Ran-GTP-dependent nucleocytoplasmic transport of NLS
      containing proteins. We showed, using immunohistochemical staining, that the
      nucleoporins Ran-binding protein 2 (RanBP2) and Ran-GTPase-activating protein 1
      (RanGAP1) have greater expression on the nuclear envelope in psoriatic epidermal
      KCs than in KCs from healthy controls. We then studied the signalling pathways
      involved in the regulation of these proteins in HaCaT cells. The two major
      downstream pathways of epidermal growth factor receptor (EGFR) signalling
      activated in psoriatic KCs are the MAPK/Erk/1/2 and the phosphatidylinositol-3
      kinase/Akt pathways. Therefore, we treated HaCaT cells with inhibitors to disrupt
      the MAP kinase kinase 1 (MEK1), PI3-kinase, or mTOR pathways. RanBP2 and RanGAP1
      protein expression levels were significantly greater in the nuclear envelope of
      HaCaT cells that were not treated with inhibitors than in cells treated with a
      combination of PI3-kinase and MEK1 inhibitors or mTOR and MEK1 inhibitors. These
      results suggest that adequate nuclear envelope expression of RanBP2 and RanGAP1
      could be a prerequisite for nucleocytoplasmic transport in KCs in psoriatic
      epidermis. 

PMID- 24438027
TI  - Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous
      extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae).
AB  - The anti-nociceptive and antioxidant activities of the Anadenantheracolubrina
      stem bark aqueous extract (AEAC) were investigated. AEAC (30 MUg/mL) reduced
      94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 MUg/mL) of
      lipid peroxidation caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride
      induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly (p <
      0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%,
      respectively) and second (48.9% and 61.9%, respectively) phases of the formalin
      test. Nociception caused by glutamate was significantly (p < 0.001) reduced by up
      to 79% at 400 mg/kg, while 56-60% of the nociceptive behaviour induced by
      capsaicin was significantly inhibited by AEAC (100-400 mg/kg). Mice treated with
      AEAC did not show changes in motor performance in the Rota-rod apparatus. It
      appears that AEAC is of pharmacological importance in treating pain due to its
      anti-nociceptive effects, which were shown to be mediated by central and
      peripheral mechanisms.

PMID- 24438028
TI  - Association between hyperglycemia in middle and late pregnancy and maternal-fetal
      outcomes: a retrospective study.
AB  - BACKGROUND: The purposes of this study were to explore whether the maternal-fetal
      outcomes differed among various types of hyperglycemia during pregnancy and
      whether the values of glycemic screening in the middle phase of pregnancy could
      predict maternal-fetal outcomes. METHODS: A retrospective study was conducted to
      study the incidence of maternal-fetal outcomes in 383 singleton pregnant women
      with diabetes or gestational diabetes admitted to our hospital from November 2007
      to March 2013. Patients were divided into three groups: DM (Type 1 and Type 2
      diabetes mellitus) group, mGDM (mild gestational diabetes mellitus) group and
      sGDM (severe gestational diabetes mellitus) group. Maternal basic
      characteristics, results of oral glucose tolerance test (OGTT), antenatal random
      glycemia and maternal-fetal outcomes were collected. Binary logistic regression
      was used to estimate the association of blood glucose with the maternal-fetal
      outcomes. Predictive accuracy was assessed by calculating the areas under the
      receiver operating characteristic curves. RESULTS: The maternal basic
      characteristics, maternal complications and neonatal complications did not differ
      significantly between DM group and sGDM group, except neonatal intensive care
      units admission (NICU). Incidences of preterm, NICU and preeclampsia were
      significantly lower in the mGDM group than in the DM and sGDM groups (P < 0.05).
      After adjusted by confounding factors, the value of OGTT 0 h could predict
      pregnancy induced hypertension (PIH) (OR = 1.24, 95% CI [1.04 to 1.46], P =
      0.015), preterm birth (OR = 1.23, 95% CI [1.03 to 1.47], P = 0.025) and
      stillbirth (OR = 1.55, 95% CI [1.14 to 2.10], P = 0.005); antenatal random
      glycemia could predict preterm birth (OR = 1.19, 95% CI [1.08 to 1.31], P <
      0.001) and stillbirth (OR = 1.41, 95% CI [1.17 to 1.71], P < 0.001). CONCLUSIONS:
      Pregnant women in the mGDM group have better outcomes than those in the DM and
      sGDM groups. The values of OGTT in the middle phase of pregnancy and antenatal
      random glycemia could predict PIH, preterm birth or stillbirth to some extent.

PMID- 24438029
TI  - Dupuytren's contracture: an analysis of outcomes of percutaneous needle
      fasciotomy versus open fasciectomy.
AB  - BACKGROUND: Percutaneous needle fasciotomy (PNF) is a minimally invasive
      technique used to manage Dupuytren's contracture. We compared outcomes of PNF
      versus open fasciectomy (OF) to examine the suitability of PNF in Australia.
      METHOD: A retrospective cohort study using two questionnaires regarding
      Dupuytren's treatment was used to assess patients with uncomplicated primary
      disease. The primary outcomes were immediate and medium-term correction of
      contracture (2-year mean follow-up to time of survey). Secondary outcomes were
      patient satisfaction and complications including tendon/nerve injury, infection,
      skin necrosis and vascular damage. RESULTS: One hundred fifty-five out of 191
      surveys were returned (81%). The final analysis included 125 cases (65%), 73 PNF
      and 52 OF. No significant differences were observed between both groups with
      regards to follow-up time, gender, smoking status, co-morbidities or preoperative
      deformity grade. No significant differences were observed in terms of immediate
      or medium-term deformity correction, tendon/nerve injury or circulatory
      complications. The postoperative infection rate was higher with OF, with these
      patients 7.57 (95% confidence interval 1.56, 36.77; P = 0.01) times as likely to
      have a postoperative infection as patients undergoing PNF. A higher number of
      patients who underwent PNF were told that they would require another operation
      (30% versus 12%; P = 0.02). Satisfaction scores were similar (OF 33.2 versus PNF
      32.6; P = 0.82). CONCLUSION: The OF and PNF procedures provide comparable
      deformity correction for uncomplicated primary Dupuytren's disease in the
      immediate perioperative period. The reduced side effect profile of PNF should
      prompt surgeons to consider incorporating it in their practice for the first-line
      management of uncomplicated primary Dupuytren's disease.

PMID- 24438030
TI  - Lucy.

PMID- 24438031
TI  - Dealing with general medical complaints in a dialysis unit.

PMID- 24438032
TI  - Seasonal variability of soil CO2 flux and its carbon isotope composition in
      Krakow urban area, Southern Poland.
AB  - As urban atmosphere is depleted of (13)CO2, its imprint should be detectable in
      the local vegetation and therefore in its CO2 respiratory emissions. This work
      was aimed at characterising strength and isotope signature of CO2 fluxes from
      soil in urban areas with varying distances from anthropogenic CO2 emissions. The
      soil CO2 flux and its delta(13)C isotope signature were measured using a chamber
      method on a monthly basis from July 2009 to May 2012 within the metropolitan area
      of Krakow, Southern Poland, at two locations representing different levels of
      anthropogenic influence: a lawn adjacent to a busy street (A) and an urban meadow
      (B). The small-scale spatial variability of the soil CO2 flux was also
      investigated at site B. Site B revealed significantly higher summer CO2 fluxes
      (by approximately 46 %) than site A, but no significant differences were found
      between their delta(13)CO2 signatures.

PMID- 24438033
TI  - Quality of care of older people living with advanced dementia in the community in
      Israel.
AB  - OBJECTIVES: To examine the quality of end-of-life (EOL) care of older people with
      advanced dementia (OPAD) living in the community. DESIGN: Retrospective cohort
      study. SETTING: The second largest preferred provider organization in Israel.
      PARTICIPANTS: Primary family caregivers of OPAD (N = 117; 52 bereaved caregivers,
      65 still caring for OPAD). MEASUREMENTS: Primary outcome measures were quality-of
      EOL-care scales regarding symptom management at the EOL with dementia (SM-EOLD)
      and comfort assessment in dying at the EOL with dementia (CAD-EOLD). RESULTS:
      Caregivers reported a mean symptom management score of 29 +/- 9.8 points (range 0
      45 points), indicating poor symptom management in the areas of pain, shortness of
      breath, fear, skin breakdown, and resistiveness to care. In a multiple regression
      model, less comorbidity, longer duration of dementia, greater caregiver
      education, and absence of caregiver depression predicted better SM-EOLD. The 52
      bereaved caregivers reported a mean CAD-EOLD score of 31.3 +/- 6.7 points (range
      14-42 points), indicating poor comfort around dying, especially difficulty
      swallowing and discomfort. CONCLUSION: Because of the high rates of suffering,
      there is a need to address the complexity and severity of symptoms and problems
      faced by OPAD in the community and their caregivers. The priorities should
      include education of healthcare providers on palliative care, focusing especially
      on symptom-management needs of OPAD and comfort around dying.

PMID- 24438034
TI  - Fragmented mitochondrial genomes of the rat lice, Polyplax asiatica and Polyplax
      spinulosa: intra-genus variation in fragmentation pattern and a possible link
      between the extent of fragmentation and the length of life cycle.
AB  - BACKGROUND: Blood-sucking lice (suborder Anoplura) parasitize eutherian mammals
      with 67% of the 540 described species found on rodents. The five species of blood
      sucking lice that infest humans and pigs have fragmented mitochondrial genomes
      and differ substantially in the extent of fragmentation. To understand whether,
      or not, any life-history factors are linked to such variation, we sequenced the
      mt genomes of Polyplax asiatica and Polyplax spinulosa, collected from the
      greater bandicoot rat, Bandicota indica, and the Asian house rat, Rattus
      tanezumi, respectively. RESULTS: We identified all of the 37 mitochondrial genes
      common to animals in Polyplax asiatica and Polyplax spinulosa. The mitochondrial
      genes of these two rat lice are on 11 circular minichromosomes; each
      minichromosome is 2-4 kb long and has 2-7 genes. The two rat lice share the same
      pattern for the distribution of the protein-coding genes and ribosomal RNA genes
      over the minichromosomes, but differ in the pattern for the distribution of 8 of
      the 22 transfer RNA genes. The mitochondrial genomes of the Polyplax rat lice
      have 3.4 genes, on average, on each minichromosome and, thus, are less fragmented
      than those of the human lice (2.1 and 2.4 genes per minichromosome), but are more
      fragmented than those of the pig lice (4.1 genes per minichromosome).
      CONCLUSIONS: Our results revealed distinct patterns of mitochondrial genome
      fragmentation within the genus Polyplax and, furthermore, indicated a possible
      inverse link between the extent of mitochondrial genome fragmentation and the
      length of life cycle of the blood-sucking lice.

PMID- 24438035
TI  - Mucoadhesive polyethylenimine-dextran sulfate nanoparticles containing Punica
      granatum peel extract as a novel sustained-release antimicrobial.
AB  - Mucoadhesive polyethylenimine-dextran sulfate nanoparticles (PDNPs) were
      developed for local oral mucosa delivery. Punica granatum peel extract (PGE) was
      loaded into PDNPs for oral malodor reduction and caries prevention. PDNPs were
      constructed using the polyelectrolyte complexation technique employing oppositely
      charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with PEG 400 as
      a stabilizer. Under optimal conditions, spherical particles of ~ 500 nm with a
      zeta potential of ~+28 mV were produced. Up to 98%, drug entrapment efficiency
      was observed. The mass ratio of PEI:DS played a significant role in controlling
      particle size and entrapment efficacy. PDNPs shown to be a good mucoadhesive drug
      delivery system as confirmed by ex vivo wash off test. In vitro dissolution
      studies revealed that PGE-loaded PDNPs manifested a prolong release
      characteristic with a burst release within 5 min. In addition, they remained
      effectively against oral bacteria.

PMID- 24438036
TI  - Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with
      distinct clinical and pathological features. Report of an EORTC Cutaneous
      Lymphoma Task Force Workshop.
AB  - AIMS: Aggressive epidermotropic cutaneous CD8(+) lymphoma is currently afforded
      provisional status in the WHO classification of lymphomas. An EORTC Workshop was
      convened to describe in detail the features of this putative neoplasm and
      evaluate its nosological status with respect to other cutaneous CD8(+) lymphomas.
      METHODS AND RESULTS: Sixty-one CD8(+) cases were analysed at the workshop;
      clinical details, often with photographs, histological sections,
      immunohistochemical results, treatment and patient outcome were discussed and
      recorded. Eighteen cases had distinct features and conformed to the diagnosis of
      aggressive epidermotropic cutaneous CD8(+) lymphoma. The patients typically
      present with widespread plaques and tumours, often ulcerated and haemorrhagic,
      and histologically have striking pagetoid epidermotrophism. A CD8(+) /CD45RA(+)
      /CD45RO(-) /CD2(-) /CD5(-) /CD56(-) phenotype, with one or more cytotoxic
      markers, was found in seven of 18 patients, with a very similar phenotype in the
      remainder. The tumours seldom involve lymph nodes, but mucosal and central
      nervous system involvement are not uncommon. The prognosis is poor, with a median
      survival of 12 months. Examples of CD8(+) mycosis fungoides, lymphomatoid
      papulosis and Woringer-Kolopp disease presented the typical features well
      documented in the CD4(+) forms of those diseases. CONCLUSIONS: Aggressive
      epidermotropic cutaneous CD8(+) lymphoma is a distinct lymphoma that warrants
      inclusion as a distinct entity in future revisions of lymphoma classifications.

PMID- 24438037
TI  - Multisite phosphorylation of 14-3-3 proteins by calcium-dependent protein
      kinases.
AB  - Plant 14-3-3 proteins are phosphorylated at multiple sites in vivo; however, the
      protein kinase(s) responsible are unknown. Of the 34 CPK (calcium-dependent
      protein kinase) paralogues in Arabidopsis thaliana, three (CPK1, CPK24 and CPK28)
      contain a canonical 14-3-3-binding motif. These three, in addition to CPK3, CPK6
      and CPK8, were tested for activity against recombinant 14-3-3 proteins chi and
      epsilon. Using an MS-based quantitative assay we demonstrate phosphorylation of
      14-3-3 chi and epsilon at a total of seven sites, one of which is an in vivo site
      discovered in Arabidopsis. CPK autophosphorylation was also comprehensively
      monitored by MS and revealed a total of 45 sites among the six CPKs analysed,
      most of which were located within the N-terminal variable and catalytic domains.
      Among these CPK autophosphorylation sites was Tyr463 within the calcium-binding
      EF-hand domain of CPK28. Of all CPKs assayed, CPK28, which contained an
      autophosphorylation site (Ser43) within a canonical 14-3-3-binding motif, showed
      the highest activity against 14-3-3 proteins. Phosphomimetic mutagenesis of Ser72
      to aspartate on 14-3-3chi, which is adjacent to the 14-3-3-binding cleft and
      conserved among all 14-3-3 isoforms, prevented 14-3-3-mediated inhibition of
      phosphorylated nitrate reductase.

PMID- 24438038
TI  - Provision of private, piped water and sewerage connections and directly observed
      handwashing of mothers in a peri-urban community of Lima, Peru.
AB  - OBJECTIVES: To estimate the association between improved water and sanitation
      access and handwashing of mothers living in a peri-urban community of Lima, Peru.
      METHODS: We observed 27 mothers directly, before and after installation of
      private, piped water and sewerage connections in the street just outside their
      housing plots, and measured changes in the proportion of faecal-hand
      contamination and hand-to-mouth transmission events with handwashing. RESULTS:
      After provision of water and sewerage connections, mothers were approximately two
      times more likely to be observed washing their hands within a minute of
      defecation, compared with when they relied on shared, external water sources and
      non-piped excreta disposal (RR = 2.14, 95% CI = 0.99-4.62). With piped water and
      sewerage available at housing plots, handwashing with or without soap occurred
      within a minute after 48% (10/21) of defecation events and within 15 min prior to
      8% (11/136) of handling food events. CONCLUSIONS: Handwashing increased following
      installation of private, piped water and sewerage connections, but its practice
      remained infrequent, particularly before food-related events. Infrastructural
      interventions should be coupled with efforts to promote hygiene and ensure access
      to water and soap at multiple on-plot locations convenient to mothers.

PMID- 24438039
TI  - The TRACTISS protocol: a randomised double blind placebo controlled clinical
      trial of anti-B-cell therapy in patients with primary Sjogren's Syndrome.
AB  - BACKGROUND: Primary Sjogren's Syndrome (PSS) mainly affects women (9:1
      female:male ratio) and is one of the commonest autoimmune diseases with a
      prevalence of 0.1 - 0.6% of adult women. For patients with PSS there is currently
      no effective therapy that can alter the progression of the disease. The aim of
      the TRACTISS study is to establish whether in patients with PSS, treatment with
      rituximab improves clinical outcomes. METHODS/DESIGN: TRACTISS is a UK multi
      centre, double-blind, randomised, controlled, parallel group trial of 110
      patients with PSS. Patients will be randomised on a 1:1 basis to receive two
      courses of either rituximab or placebo infusion in addition to standard therapy,
      and will be followed up for up to 48 weeks. The primary objective is to assess
      the extent to which rituximab improves symptoms of fatigue and oral dryness.
      Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow,
      patient quality of life, measures of disease damage and disease activity,
      serological and peripheral blood biomarkers, and glandular histology and
      composition. DISCUSSION: The TRACTISS trial will provide direct evidence as to
      whether rituximab in patients with PSS leads to an improvement in patient
      symptoms and a reduction in disease damage and activity. TRIAL REGISTRATION:
      UKCRN Portfolio ID: 9809 ISRCTN65360827.

PMID- 24438040
TI  - Gene expression change in human dental pulp cells exposed to a low-level toxic
      concentration of triethylene glycol dimethacrylate: an RNA-seq analysis.
AB  - Dental composite resin restoration for defective tooth may lead unpolymerized
      resin monomers to be leached into dental pulp tissue. The aim of this study was
      to investigate the early gene expression change over time of human dental pulp
      cells (HDPCs) treated with a low-level toxic concentration of Triethylene Glycol
      Dimethacrylate (TEGDMA), a common dental resin monomer, by adopting the novel
      high-throughput transcriptome analysis of RNA-seq. The low-level toxic
      concentration of TEGDMA was determined through MTT assays with serially diluted
      concentrations. After the HDPCs were exposed to TEGDMA for 6, 12, 24 or 48 hr,
      the total RNA of the samples was prepared for RNA-seq. qRT-PCR for several genes
      was performed for validation of RNA-seq results. In the treated group, 1280 genes
      were differentially expressed compared with the control group. Five patterns of
      time-series gene expression profiles were identified through k-means clustering
      analysis. Angiogenesis, cell adhesion and migration, extracellular matrix
      organization, response to extracellular stimulus, inflammatory response and
      mineralization-related process were major gene ontology terms in functional
      annotation clustering. HMOX1, OSGIN1, SMN2, SRXN1 AKR1C1, SPP1 and TOMM40L were
      highly up-regulated genes, and WRAP53 and CCL2 were highly down-regulated genes
      over time. qRT-PCR for several genes exhibited a high level of agreement with RNA
      seq. TEGDMA induced the HDPCs to show massive and dynamic gene expression changes
      over time. The previously suggested toxic mechanism of TEGDMA was not only
      verified, but new genes whose functions have yet to be determined were also
      found. 

PMID- 24438041
TI  - Emergency physician radiation risk communication: a role for shared decision
      making.

PMID- 24438042
TI  - Extraosseous calcification in end-stage renal disease: from visceral organs to
      vasculature.
AB  - In earlier days, periarticular accumulations of calcium phosphate causing tumor
      like depositions were considered the result of passive precipitation and referred
      to as metastatic calcifications. From sophisticated computer tomographic studies
      and growing insight, we have learned that calcifications in the cardiovascular
      system are far more threatening and in fact one of the most important sequela of
      end-stage renal disease. The histologic characteristic of uremia-related
      calcification is arteriosclerosis of the media. In addition, there is
      atherosclerosis of the intima, due to the high prevalence of classic
      cardiovascular risk factors in renal disease. The two vascular features can
      frequently exist at different sites in the vasculature. Novel diagnostic
      techniques are helping to elucidate the pathogenetic mechanisms of active
      conversion of vascular smooth muscle cells to osteochondritic cells. Through this
      process, extensive calcification of the central and peripheral vasculature
      ensues, influenced by different promotors and inhibitors. Calciphylaxis is a
      special form of extraosseous calcification leading to skin necrosis. The factors
      that trigger the development of calciphylaxis are not completely understood, but
      this syndrome shares part of the pathophysiologic basis of extraosseous
      calcification in general. However, the therapeutic approach must be prompt and
      aggressive, because of the poor prognosis. Frequently, a fatal outcome cannot be
      avoided in calciphylaxis. 

PMID- 24438043
TI  - Extracorporeal ("ex vivo") connection of pig kidneys to humans. I. Clinical data
      and studies of platelet destruction.
AB  - The pioneering experiment by Welsh et al. (Immunological Lett 1991:29:167-170)
      connecting a pig kidney to the human circulation has been repeated in a modified
      manner. Two volunteer dialysis patients were pretreated by daily plasmapheresis
      on days -2,-1, and 0 to remove the naturally occurring anti-pig xenoantibodies.
      The anti-pig lymphocytotoxic liters were reduced from 1:8 to 1:2 in patient 1 and
      from 1:8 to 1:1 in patient 2. No steroids or immunosuppressive drugs were
      administrated before or during the experiments. A sterile pig kidney was
      extracorporeally ("ex vivo") connected to the patients a/v fistula using an
      arterial and a venous pump similar to a dialysis. The two experiments gave
      different results. In the first experiment the perfusion pressure was kept at 100
      mmHg for the initial 25 min by reducing the pump speed until the minimum blood
      flow of 30 ml/min was reached. Thereafter, the pressure rose continuously and the
      experiment was terminated at 65 min at a perfusion pressure of 200 mmHg. The
      patient did not feel any discomfort during the perfusion. In the second
      experiment, a stable blood flow of 200 ml/min was reached at a pressure of 100
      mmHg after a few minutes. The perfusion was terminated at 15 min when the patient
      developed chest and abdominal pain, hypotension, and electrocardiographic signs
      of myocardial ischemia. The patient recovered quickly. In the first experiment,
      small volumes of clear urine was produced until the pressure rose above 100 mmHg,
      which resulted in hematuria. In the second experiment clear urine (4 ml/min) was
      produced. (51)Chromium clearance values were after 15 min <1 ml/min for kidney 1
      and 12 ml/min (8 ml/min/100 g) for kidney 2. A drastic reduction in platelet
      count (128 to 48 and 64 to 8 * 10(9)/1, respectively) during the passage through
      the kidney was found in blood samples collected simultaneously before and after
      the organ. No change in hemoglobin values and leucocyte counts were found. Light-
      and electron-microscopical analysis of the kidney tissues revealed for kidney 1
      focal areas with obliteration of the glomerular and peritubular capillaries by
      platelets and PMN cells and severe damage of the endothelial cells comparable to
      a picture of a hyperacute rejection. In kidney 2, all vessels were patent but in
      the capillaries large amount of membrane fragments were detected by electron
      microscopy and a discrete damage of the endothelial cells were seen in some
      segments. No intact platelets were present in the vascular tree. These human
      experiments support the hypothesis that hyperacute rejection of pig to human
      xenografts is delayed in time by removal of the preformed anti-pig
      xenoantibodies. A new finding was a very rapid destruction of platelets occurring
      in the kidney of patient 2 who had very low liters of xenoantibodies. The humoral
      immune response is described in detail in an accompanying paper (Rydberg et al.,
      this issue). 

PMID- 24438045
TI  - Connecting social environment variables to the onset of major specific health
      outcomes.
AB  - OBJECTIVE: The present research examined the effects of the social environment on
      the onset of specific health ailments. DESIGN: Using data from the Health and
      Retirement Study, we examined participants' responses to social environment
      questions in 2006 as predictors of onset of different health conditions over the
      next four years. MAIN OUTCOME MEASURES: Healthy participants (n = 7514) reported
      on their number of social partners, interaction frequency, positive social
      support and negative social support with respect to both their family and
      friends. These variables were used to predict onset of seven conditions in 2010:
      high blood pressure, heart condition, lung disease, cancer, stroke, diabetes and
      arthritis. RESULTS: Logistic regressions indicated that the social environment
      provided some predictive value for onset of most health outcomes, with more
      positive and less negative social support appearing to buffer against onset.
      Social environmental variables related to friendships appeared to play a greater
      role than the family indicators. However, no variable proved universally
      adaptive, and social indicators had little value in predicting onset of chronic
      conditions. CONCLUSION: The current findings point to the potential for the
      social environment to influence later health, while demonstrating the nuanced
      role that our social lives play with respect to health.

PMID- 24438044
TI  - Earlier age at menarche is associated with higher diabetes risk and
      cardiometabolic disease risk factors in Brazilian adults: Brazilian Longitudinal
      Study of Adult Health (ELSA-Brasil).
AB  - OBJECTIVES: Early menarche has been linked to higher risk of type 2 diabetes in
      Western and Asian societies, yet whether age at menarche is associated with
      diabetes in Latin America, where puberty and diabetes may have different life
      courses, is unknown. We tested the hypothesis that earlier menarche is associated
      with higher diabetes risk in Brazilian adults. METHODS: We used data from 8,075
      women aged 35-74 years in the Brazilian Longitudinal Study of Adult Health (ELSA
      Brasil) who had complete information on age at menarche, diabetes status, and
      covariates. Diabetes was defined based on self-reported physician diagnosis,
      medication use, and laboratory variables (fasting glucose, 2-hour glucose, and
      glycated hemoglobin). Poisson regression was used to generate risk ratios (RR)
      and 95% confidence intervals (CI). RESULTS: Menarche onset < 11 years [vs. 13-14
      years (referent)] was associated with higher risk of diabetes (RR = 1.34; 95% CI:
      1.14-1.57) after adjusting for sociodemographic factors, maternal education,
      maternal and paternal diabetes, and birth weight. This persisted after further
      control for BMI at age 20 years and relative leg length. Additionally, among
      those not taking diabetes medications, earlier menarche [<11 years vs. 13-14
      years (referent)] was associated with higher % glycated hemoglobin (p < 0.001),
      alanine aminotransferase (p < 0.001), triglycerides (p < 0.001), C-reactive
      protein (p = 0.003), waist circumference (p < 0.001), and BMI measured at
      baseline exam (p < 0.001). CONCLUSION: These findings support the hypothesis that
      earlier menarche is associated with greater risk for adult diabetes and
      cardiometabolic disease in the Brazilian context.

PMID- 24438046
TI  - Case control study of risk factors for frozen shoulder in China.
AB  - AIM: Frozen shoulder is a common self-limiting regional skeletal problem of
      unclear pathogenesis. It usually has an insidious onset and follows a protracted
      course. The aim of this study was to assess the prevalence and related risk
      factors for frozen shoulder in Shanghai, China. METHODS: We performed a hospital
      based case-control study involving 182 patients with pathologically diagnosed
      frozen shoulder and 196 patients hospitalized during the same time period with
      non-shoulder related complaints who were recruited as controls. Information on
      potential risk factors was collected on both case and control groups through
      questionnaires and face-to-face interview. Univariate and multivariate logistic
      regression analyses were performed. RESULTS: Among the frozen shoulder patients,
      24.2% had diabetes and 16.5% had history of shoulder trauma. Multivariate
      analysis suggested that diabetes and history of slight trauma were independent
      risk factors for the disease. The frozen shoulder patients also had a higher
      prevalence of thyroid disease, increased body mass index and cervical spondylosis
      than the controls. The incidence of frozen shoulder was higher in female compared
      to male patients. No significant difference was found in occupations, physical
      exercise, cholecystitis, history of surgical and ischemic heart disease between
      the frozen shoulder group and the control group. CONCLUSIONS: The findings in the
      present study indicate that diabetes, history of slight shoulder trauma, thyroid
      disease, increased body mass index and cervical spondylosis are factors
      significantly associated with increased frozen shoulder risk among individuals
      within the area of Shanghai, China.

PMID- 24438048
TI  - A case of denial.

PMID- 24438047
TI  - Neuroprotective effect of the proanthocyanidin-rich fraction in experimental
      model of spinal cord injury.
AB  - OBJECTIVES: In this study, we evaluated the effect of the proanthocyanidins-rich
      fraction (PRF) obtained from Croton celtidifolius bark in an experimental animal
      model of spinal cord injury and cell death induced by glutamate. METHODS:
      Experiments were conducted using adult male Wistar rats (10 weeks old and
      weighing 270-300g). Experimental groups were randomly allocated into the
      following groups: spinal cord injury (SCI) + vehicle group: rats were subjected
      to SCI plus intraperitoneal administration of vehicle (saline 10 ml/kg); SCI +
      PRF: rats were subjected to SCI plus intraperitoneal administration of PRF (10
      mg/kg) at 1 and 6 h after injury and sham operated. KEY FINDINGS: The treatment
      with the proanthocyanidin-rich fraction significantly improved not only motor
      recovery and grip force but also H2 O2 or glutamate-induced cell death and
      reactive oxygen species generation induced by glutamate in dorsal root ganglion
      cells. In this study we demonstrate that the neuroprotective effect triggered by
      the proanthocyanidins-rich fraction appears to be mediated in part by the
      inhibition of N-methyl-D-aspartate-type glutamate receptors. CONCLUSIONS: Taken
      together, our results demonstrate that PRF treatment ameliorates spinal cord
      injury and glutamatergic excitotoxicity and could have a potential therapeutic
      use.

PMID- 24438049
TI  - Impact of geographic location on surgical outcomes of women with breast cancer.
AB  - BACKGROUND: The aim of this study is to use the Breast Surgeons of Australia and
      New Zealand Quality Audit to evaluate the diagnostic work up and surgical
      treatment path for Australian women with early breast cancer in relation to
      geographic location. METHODS: We accessed data on patient geographic
      demographics, diagnostic and surgical procedures and cancer characteristics in
      115,872 episodes of early breast cancer reported to the Quality Audit between
      1998 and 2012. Tumour size, grade and number, lymph node positivity and
      lymphovascular invasion are the major prognostic factors adjusted for. RESULTS:
      Core biopsy is the most frequently performed diagnostic method and open biopsy
      the least (P=0.001). Remote locations have the highest proportion of open
      biopsies and cities the lowest (13.8 versus 9.8%, P=0.001). The outer
      regional/remote patient group has a higher likelihood of an open biopsy than city
      patients (odds ratio 1.5; 95% confidence interval 1.1-2.2 P=0.02). Reconstruction
      rates are low throughout ranging from 3 to 4% (P=0.001). Cities have the highest
      proportion of no surgery (1.5%, P=0.001). Cities have the highest proportion of
      breast conserving surgery and the remote the lowest (64.5% versus 29.9%,
      P=0.001). Outer regional locations have the highest proportion of mastectomies
      and cities the lowest (38 versus 29.9%, P=0.001). The likelihood of receiving
      radiotherapy is associated with geographic location of residence and geographic
      distribution of the radiotherapy facility (P=0.002, P=0.001). CONCLUSION:
      Geographic location of residence is associated with the diagnostic work up and
      surgical treatment of Australian women with early breast cancer.

PMID- 24438050
TI  - (238)U and total radioactivity in drinking waters in Van province, Turkey.
AB  - As part of the national survey to evaluate natural radioactivity in the
      environment, concentration levels of total radioactivity and natural uranium have
      been analysed in drinking water samples. A survey to study natural radioactivity
      in drinking waters was carried out in the Van province, East Turkey. Twenty-three
      samples of drinking water were collected in the Van province and analysed for
      total alpha, total beta and (238)U activity. The total alpha and total beta
      activities were counted by using the alpha/beta counter of the multi-detector low
      background system (PIC MPC-9604), and the (238)U concentrations were determined
      by inductively coupled plasma-mass spectrometry (Thermo Scientific Element 2).
      The samples were categorised according to origin: tap, spring or mineral supply.
      The activity concentrations for total alpha were found to range from 0.002 to
      0.030 Bq L(-1) and for total beta from 0.023 to 1.351 Bq L(-1). Uranium
      concentrations ranging from 0.562 to 14.710 MUg L(-1) were observed in drinking
      waters. Following the World Health Organisation rules, all investigated waters
      can be used as drinking water.

PMID- 24438052
TI  - Task meaningfulness and degree of cognitive impairment: do they affect self
      generated learning in persons with multiple sclerosis?
AB  - Self-generated learning has been shown to improve memory performance in persons
      with multiple sclerosis (MS), although little is known about the variables that
      influence its efficacy. This study examined whether task meaningfulness and
      degree of cognitive impairment influence the effectiveness of self-generation in
      improving learning and memory in MS. A mixed design with both a within- and
      between-subject factors was employed. The setting was a nonprofit rehabilitation
      research institution. Participants included 35 persons with MS with moderate to
      severe learning and memory impairments (SEVERE-MS), and 35 persons with little to
      no impairment (MILD-MS). Participants in both groups learned two types of tasks
      (functional everyday tasks and laboratory tasks), each in two learning conditions
      (Provided and Generated). Participants were required to recall the information
      immediately, 30 minutes, and 1 week following initial learning. Significantly
      more words were recalled from the generated condition relative to the provided
      condition. Additionally, self-generation was more effective in recall on the
      functional tasks compared to the laboratory tasks, consistent for both memory
      impaired and non-impaired participants. Self-generation may be influenced by
      variables such as task meaningfulness during learning and memory. In addition,
      type of task (functional versus laboratory) has a significant effect on memory.
      Implications for cognitive rehabilitation in MS are discussed. 

PMID- 24438051
TI  - Economic evaluation of access to musculoskeletal care: the case of waiting for
      total knee arthroplasty.
AB  - BACKGROUND: The projected demand for total knee arthroplasty is staggering. At
      its root, the solution involves increasing supply or decreasing demand. Other
      developed nations have used rationing and wait times to distribute this service.
      However, economic impact and cost-effectiveness of waiting for TKA is unknown.
      METHODS: A Markov decision model was constructed for a cost-utility analysis of
      three treatment strategies for end-stage knee osteoarthritis: 1) TKA without
      delay, 2) a waiting period with no non-operative treatment and 3) a non-operative
      treatment bridge during that waiting period in a cohort of 60 year-old patients.
      Outcome probabilities and effectiveness were derived from the literature. Costs
      were estimated from the societal perspective with national average Medicare
      reimbursement. Effectiveness was expressed in quality-adjusted life years (QALYs)
      gained. Principal outcome measures were average incremental costs, effectiveness,
      and quality-adjusted life years; and net health benefits. RESULTS: In the base
      case, a 2-year wait-time both with and without a non-operative treatment bridge
      resulted in a lower number of average QALYs gained (11.57 (no bridge) and 11.95
      (bridge) vs. 12.14 (no delay). The average cost was $1,660 higher for TKA without
      delay than wait-time with no bridge, but $1,810 less than wait-time with non
      operative bridge. The incremental cost-effectiveness ratio comparing wait-time
      with no bridge to TKA without delay was $2,901/QALY. When comparing TKA without
      delay to waiting with non-operative bridge, TKA without delay produced greater
      utility at a lower cost to society. CONCLUSIONS: TKA without delay is the
      preferred cost-effective treatment strategy when compared to a waiting for TKA
      without non-operative bridge. TKA without delay is cost saving when a non
      operative bridge is used during the waiting period. As it is unlikely that
      patients waiting for TKA would not receive non-operative treatment, TKA without
      delay may be an overall cost-saving health care delivery strategy. Policies aimed
      at increasing the supply of TKA should be considered as savings exist that could
      indirectly fund those strategies.

PMID- 24438053
TI  - Quantifying filariasis and malaria control activities in relation to lymphatic
      filariasis elimination: a multiple intervention score map (MISM) for Malawi.
AB  - OBJECTIVE: To quantify the geographical extent of filariasis and malaria control
      interventions impacting lymphatic filariasis (LF) in Malawi and to produce a
      multiple intervention score map (MISM) for prioritising surveillance and
      intervention strategies. METHODS: Interventions included mass drug administration
      (MDA) for LF and onchocerciasis, and bed nets and indoor residual spraying (IRS)
      for malaria. District and subdistrict-level data were obtained from the Ministry
      of Health in Malawi, the Demographic and Health Survey (DHS) and President's
      Malaria Initiative reports. Single intervention scores were calculated for each
      variable based on population coverage thresholds, and these were combined in a
      weighted sum to form a multiple intervention score, which was then used to
      produce maps, that is MISMs. Districts were further classified into four groups
      based on the combination of their baseline LF prevalence and multiple
      intervention score. RESULTS: The district- and subdistrict-level MISMs
      highlighted specific areas that have received high and low coverage of LF
      impacting interventions. High coverage areas included the LF-onchocerciasis
      endemic areas in the southern region of the country and areas along the shores of
      Lake Malawi, where malaria vector control had been prioritised. Three districts
      with high baseline LF prevalence measures but low coverage of multiple
      interventions were identified and considered to be most at risk of ongoing
      transmission or re-emergence. CONCLUSIONS: These maps and district
      classifications will be used by LF programme managers to identify and target high
      risk areas that may not have received adequate LF-impacting interventions to
      interrupt the transmission of the disease.

PMID- 24438054
TI  - The transcriptome of the NZ endemic sea urchin Kina (Evechinus chloroticus).
AB  - BACKGROUND: Sea urchins are studied as model organisms for developmental and
      systems biology and also produce highly valued food products. Evechinus
      chloroticus (Kina) is a sea urchin species that is indigenous to New Zealand. It
      is the type member of the Evechinus genus based on its morphological
      characteristics. Previous research has focused on identifying physical factors
      affecting commercial roe quality of E. chloroticus, but there is almost no
      genetic information available for E. chloroticus. E. chloroticus is the only
      species in its genus and has yet to be subject to molecular phylogenetic
      analysis. RESULTS: In this study we performed a de novo transcriptome assembly of
      Illumina sequencing data. A total of 123 million 100 base length paired-end reads
      were generated using RNA-Seq libraries from a range of E. chloroticus tissues
      from two individuals obtained from Fiordland, New Zealand. The assembly resulted
      in a set of 75,002 transcripts with an accepted read coverage and length, of
      which 24,655 transcripts could be functionally annotated using protein
      similarity. Transcripts could be further annotated with Gene Ontology, KEGG
      Orthology and InterPro terms. With this sequence data we could perform the first
      phylogenetic analysis of E. chloroticus to other species of its family using
      multiple genes. When sequences for the mitochondrial nitrogen dehydrogenase genes
      were compared, E. chloroticus remained outside of a family level clade, which
      indicated E. chloroticus is indeed a genetically distinct genus within its
      family. CONCLUSIONS: This study has produced a large set of E. chloroticus
      transcripts/proteins along with functional annotations, vastly increasing the
      amount of genomic data available for this species. This provides a resource for
      current and future studies on E. chloroticus, either to increase its commercial
      value, or its use as a model organism. The phylogenetic results provide a basis
      for further analysis of relationships between E. chloroticus, its family members,
      and its evolutionary history.

PMID- 24438056
TI  - Mapping publication status and exploring hotspots in a research field: chronic
      disease self-management.
AB  - AIM: To provide insight into the characteristics of chronic disease self
      management by mapping publication status and exploring hotspots. BACKGROUND:
      Chronic disease is becoming a major public health issue worldwide, highlighting
      the importance of self-management in this area. Despite the volume and variety of
      publications, little is known about how 'chronic disease self-management' has
      developed, since the first publication 40 years ago. Such is the number of
      publications in the area, that there is a need for a systematic bibliographic
      examination to enable clinicians and researchers to navigate this literature.
      DESIGN: A bibliometric analysis of publications was used. METHODS: Publication
      status was achieved using BICOMB software, whereas hotspots were identified with
      Ucinet software. A search of PubMed was conducted for papers published between
      1971-2012. RESULTS: By 2011, the number of publications reached 696, a fourfold
      increase from the previous 10 years, of which 75% came from the USA and UK. There
      were 1284 journals, which published chronic disease self-management research,
      involving various disciplines. The research hotspots highlighted various self
      management strategies for the following: diabetes; cardiac vascular and pulmonary
      chronic disease; pain relief for neoplasms; and obesity. Psychological adjustment
      was a permeating theme in self-management processes as was using internet-based
      interventions. CONCLUSION: Self-management in chronic disease publication has
      been most evident in developed countries. The bibliographic mapping and
      identification of publication hotspots provides scholars and practitioners with
      key target journals, as well as a rigorous overview of the field for use in
      further research, evidence-based practice and health policy development.

PMID- 24438055
TI  - Stability of the human pregnane X receptor is regulated by E3 ligase UBR5 and
      serine/threonine kinase DYRK2.
AB  - The hPXR (human pregnane X receptor), a major chemical toxin sensor, is a ligand
      induced transcription factor activated by various xenobiotics and toxins,
      resulting in the transcriptional up-regulation of detoxifying enzymes. To date,
      little is known about the upstream regulation of hPXR. Using MS analysis and a
      kinome-wide siRNA screen, we report that the E3 ligase UBR5 (ubiquitin protein
      ligase E3 component n-recognin 5) and DYRK2 (dual-specificity tyrosine
      phosphorylation-regulated kinase 2) regulate hPXR stability. UBR5 knockdown
      resulted in accumulation of cellular hPXR and a concomitant increase in hPXR
      activity, whereas the rescue of UBR5 knockdown decreased the cellular hPXR level
      and activity. Importantly, UBR5 exerted its effect in concert with the
      serine/threonine kinase DYRK2, as the knockdown of DYRK2 phenocopied UBR5
      knockdown. hPXR was shown to be a substrate for DYRK2, and DYRK2-dependent
      phosphorylation of hPXR facilitated its subsequent ubiquitination by UBR5. This
      is the first report of the post-translational regulation of hPXR via
      phosphorylation-facilitated ubiquitination by DYRK2 and UBR5. The results of the
      present study reveal the role of the ubiquitin-proteasomal pathway in modulating
      hPXR activity and indicate that pharmacological inhibitors of the ubiquitin
      proteasomal pathway that regulate hPXR stability may negatively affect treatment
      outcome from unintended hPXR-mediated drug-drug interactions.

PMID- 24438057
TI  - How is the heart best protected in chronic dialysis patients?: Control of
      extracellular volume.

PMID- 24438058
TI  - Extracorporeal ("ex vivo") connection of pig kidneys to humans. II. The anti-pig
      antibody response.
AB  - Pig kidneys were extracorporeally "ex vivo" connected to the circulation of two
      volunteer male dialysis patients (Breimer et al., this issue). The patients were
      pretreated by daily plasmapheresis for 3 consecutive days, which reduced the anti
      pig lymphocytotoxic titer from 8 to 2 in the first patient and from 8 to 1 in the
      second patient. The anti-pig hemagglutinating titers were reduced from 32 to 4 in
      the first patient and from 2 to 1 in the second patient. No drugs, except
      heparin, were given. The perfusion lasted for 65 min in patient 1 and the
      experiment was terminated due to increased vascular resistance in the pig kidney.
      Ultrastructural investigation showed a picture similar to a hyperacute vascular
      rejection. Immunohistochemical studies showed a weak staining of IgM antibodies,
      but no IgG in the small arteries and glomeruli. The pig kidney of patient 2 was
      perfused for 15 min and the experiment terminated due to serious side effects of
      the patient. Light and electron microscopical investigation showed virtually no
      structural changes of the kidney tissue and immunostaining for human antibodies
      was negative. In both patients, serum samples collected 2-5 weeks postperfusion
      showed a strong anti-pig antibody titer rise (up to 512) which thereafter
      declined but stabilized on a higher level than before the experiment. The
      antibody response in the two patients was different. In patient 1, the major anti
      pig antibodies directed to carbohydrate antigens were of IgG (IgG1 and IgG2
      subclasses) type, while the IgM response was less prominent and virtually no IgA
      antibodies were produced. Despite the short duration of the perfusion in patient
      2, a humoral immune response was seen that was mainly confined to the IgA
      immunoglobulin class (IgA1 subclass). Blood group glycospingolipid fractions,
      prepared from the contralateral kidney of the donor pigs, were used for
      immunostaining with patient serum samples. In both patients, the antibodies
      produced after the perfusion, mainly recognized the Galalpha1-3Gal epitope both
      as part of the "linear B" pentasaccharide but also on more complex carbohydrate
      structures. Patient 1 was HLA-immunized before the experiment due to a kidney
      allograft and had a panel reactivity of 85% before the perfusion. No change in
      the panel reactivity of HLA-antibodies was found after the perfusion experiments.
      Patient 2 had no HLA antibodies before and remained negative after the perfusion.
      Patient serum samples collected before and after the perfusion were tested for
      reactivity against human endothelial cell lines. No antibodies were generated. 

PMID- 24438059
TI  - Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point
      mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009-2013.
AB  - Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema
      pallidum, have been reported to cause treatment failures in patients receiving
      azithromycin for syphilis. Genotyping of T. pallidum strains sequentially
      isolated from patients with recurrent syphilis is rarely performed. From
      September 2009 to August 2013, we collected 658 clinical specimens from 375
      patients who presented with syphilis for genotyping to examine the number of 60
      bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr)
      polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by
      restriction fragment length polymorphism. Treponemal DNA was identified in 45.2%
      (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268
      (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for
      macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no
      A2059G mutation was identified. A total of 14 strains of T. pallidum were
      identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant
      strains. Forty patients who presented with recurrent episodes of syphilis had T.
      pallidum DNA identified from the initial and subsequent episodes, with five cases
      showing strain discrepancies. One patient had two strains identified from
      different clinical specimens collected in the same episode. Our findings show
      that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence
      of T. pallidum strains that show A2058G or A2059G mutation remains low. Different
      genotypes of T. pallidum can be identified in patients with recurrent episodes of
      syphilis. 

PMID- 24438061
TI  - Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell
      lymphomas.
AB  - BACKGROUND: Alemtuzumab has been proposed as salvage therapy for refractory
      cutaneous T-cell lymphomas (CTCLs). Long-term follow-up data are scarce.
      OBJECTIVES: To assess the efficacy and safety of alemtuzumab in the treatment of
      advanced CTCL. METHODS: A multicentre retrospective analysis was carried out of
      39 patients with advanced CTCL treated with alemtuzumab between 2003 and 2013.
      RESULTS: Thirty-nine patients (median age 62 years, range 20-83) with Sezary
      syndrome (SS, n = 23) or advanced mycosis fungoides (MF, n = 16) received
      alemtuzumab 30 mg two to three times per week for a median duration of 12 weeks
      (range 1-35). Fifteen patients received maintenance therapy for a median duration
      of 24 weeks (range 6-277). Eleven patients (28%) had transformed disease (MF, n =
      10; SS, n = 1). After a median follow-up of 24 months (range 0.3-124), eight
      patients (21%) were still alive. The overall response rate was 51% in the whole
      study group (partial response, n = 13; complete response, n = 7); 70% in patients
      with SS and 25% in patients with MF (P = 0.009). The median time to progression
      was 3.4 months (range 0.4-42). Six patients (15%; SS, n = 5; MF, n = 1) remained
      progression free for > 2 years (median 56 months, range 28-117). Five patients
      experienced cutaneous large T-cell transformation during alemtuzumab treatment
      and one patient developed primary cutaneous large B-cell lymphoma. Twenty-four
      patients (62%) had a grade three or higher infectious adverse event and 10 (26%)
      a haematological toxicity, which led to treatment discontinuation in 17 cases
      (44%) and death in two (5%). CONCLUSIONS: Alemtuzumab may induce long-term
      remission in SS but seems ineffective in MF and transformed CTCL.

PMID- 24438062
TI  - Appropriateness of breast cancer care: a changing landscape focusing on proper
      utilization of resources and patients' choices.

PMID- 24438060
TI  - Plasma 25-hydroxyvitamin D3 is associated with decreased risk of postmenopausal
      breast cancer in whites: a nested case-control study in the multiethnic cohort
      study.
AB  - BACKGROUND: Higher sunlight exposure is correlated with lower incidence of breast
      cancer in ecological studies, but findings from prospective studies regarding the
      association of circulating levels of vitamin D with the risk of breast cancer
      have been null. The objective of this study was to examine the relation between
      plasma levels of vitamin D and the risk of postmenopausal breast cancer. METHODS:
      We conducted a nested case-control study within the Multiethnic Cohort Study of
      five race/ethnic groups (white, African-American, Native Hawaiian, Japanese, and
      Latino) from Hawaii and Los Angeles between 2001 and 2006. Pre-diagnostic plasma
      levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3] and
      25(OH)D (sum of 25(OH)D2 and 25(OH)D3) were examined among 707 postmenopausal
      breast cancer cases and matched controls. RESULTS: Using conditional logistic
      regression models, 20 ng/mL increases of plasma 25(OH)D3 (odds ratio (OR) 0.28;
      95% confidence interval (CI) 0.14-0.56) and 25(OH)D (OR 0.43; 95% CI 0.23-0.80)
      were inversely associated with breast cancer risk among white women, but not
      among women in other race/ethnic groups. Using two-segmented, piecewise-linear
      logistic regression models, the change-points of the ORs, either for 25(OH)D3 or
      for 25(OH)D, were detected as 20 ng/mL among whites. CONCLUSIONS: Circulating
      25(OH)D3 and 25(OH)D were associated with a reduced risk of postmenopausal breast
      cancer among whites, but not in other ethnic groups, who reside in low latitude
      regions.

PMID- 24438063
TI  - Pathological evaluation of nipple-sparing mastectomies with emphasis on occult
      nipple involvement: the Weill-Cornell experience with 325 cases.
AB  - Nipple-sparing mastectomy (NSM) is an increasingly utilized surgical option in
      managing breast carcinoma; however, data on malignant involvement of a separately
      submitted nipple margin are scant. Consecutive NSM, including those performed for
      therapeutic and prophylactic purposes, over a 4-year period (2007-2011), were
      studied. A separately submitted nipple margin was evaluated by permanent H&E
      preparations and via frozen section evaluation whenever requested. 325
      consecutive NSM specimens, 208 (64%) therapeutic-NSM, and 117 (36%) prophylactic
      NSM were studied. All nipples were clinically unremarkable. 86% (179/208) of
      nipple margins from therapeutic-NSM and 100% (117/117) from prophylactic-NSM
      showed no histopathologic abnormality. 14% (29/208) of nipple margins from
      therapeutic-NSM and no nipple margin from prophylactic-NSM showed malignancy.
      Frozen section evaluation was performed in 188/325 NSM (58%) with a sensitivity
      of 64% and specificity of 99%. Central tumor location and stage N2/N3 lymph node
      status were significantly associated with nipple margin positivity (chi(2) <=
      0.05). Subsequent nipple resection was performed in 69% (20/29) of nipple margin
      positive cases with residual malignancy found in 40% (8/20, including three cases
      of invasive carcinoma). In a mean follow-up of 33 months, one invasive carcinoma
      recurred in the "saved" nipple, 36 months after therapeutic-NSM. 14% (29/208) of
      nipple margins in therapeutic-NSM and no nipple margin (0/117) in prophylactic
      NSM showed malignancy. Central tumor location and N2/N3 stage were significantly
      associated with nipple margin positivity (chi(2) <= 0.05).

PMID- 24438064
TI  - Time to begin adjuvant chemotherapy and survival in breast cancer patients: a
      retrospective observational study using latent class analysis.
AB  - The analysis of time to treatment data and the evaluation of subsequent effects
      on health outcomes can be complex due to the nature of the data and the
      relationships amongst the variables. This study proposes an alternative method of
      analyzing such data using latent class analysis (LCA). The association between
      time to begin adjuvant chemotherapy after breast cancer surgery and survival was
      investigated using both "traditional" regression analysis and LCA. Women with
      breast cancer undergoing surgery and subsequent adjuvant chemotherapy in two
      English regions between January 01, 1998 and December 31, 2004 were identified
      from a linked cancer registry-Hospital Episode Statistics dataset (n = 10,366).
      Patient, tumor, and treatment information were extracted. A Cox proportional
      hazards model was used to analyze 5-year survival using regression analysis and
      LCA. Using "traditional" regression analysis, women beginning chemotherapy >10
      weeks after surgery had worse survival in region 1 (HR = 1.49, 95% CI 1.13-1.95
      compared to <3 weeks) but not region 2. LCA split the women into three groups
      representing short, medium, and long waits. The median time to begin chemotherapy
      in the "long" wait group was 70 (region 1) and 57 (region 2) days. In this group,
      increased time to begin chemotherapy was associated with worse survival (region 1
      HR = 1.15, 95% CI 1.11-1.18; region 2 HR = 1.08, 95% CI 1.03-1.13 per week
      increase). LCA identified a group of 13-15% of women for whom a longer time to
      begin chemotherapy had an adverse effect on survival. This methodology provides
      an excellent framework in which to examine complex associations between the
      delivery of patient care and patient outcomes.

PMID- 24438065
TI  - Axillary lymph node status and prognosis in multifocal and multicentric breast
      carcinoma.
AB  - According to tumor-node-metastasis classification, tumor size should be based
      only on the largest tumor for multifocal and multicentric (MFMC) carcinomas. We
      estimated tumor size of MFMC carcinoma using either largest dimension of the
      largest tumor (dominant tumor size) or sum of the largest dimension of all tumors
      (aggregate tumor size), and compared the risk of axillary lymph node metastasis
      and prognosis between MFMC and unifocal carcinoma. We retrospectively reviewed
      the file records of 3,616 patients with MFMC (258 patients, 7.1%) and unifocal
      (3,358 patients) carcinoma. In T1 and T2 tumor subgroups, using dominant (p =
      0.001 and p < 0.001) and aggregate (p = 0.017 and p = 0.004) tumor size axilla
      positivity ratio was significantly higher in MFMC carcinoma compared with
      unifocal carcinoma. In stage I and II disease classified according to either
      dominant or aggregate tumor size, there was no significant survival difference
      between MFMC and unifocal carcinoma patients. In patients with stage III disease
      by dominant and aggregate tumor size disease-free survival was significantly
      worse in MFMC carcinoma compared with unifocal carcinoma (p = 0.036 and p =
      0.041); multifocality and multicentricity had no independent prognostic
      significance (p = 0.074 and p = 0.079). The risk of axillary metastasis in MFMC
      carcinoma was higher than unifocal carcinoma, regardless of the method employed
      for tumor size estimation. MFMC carcinoma staged according to either dominant or
      aggregate tumor size had similar survival with unifocal carcinoma. We recommend
      using the largest dimension of the largest tumor in estimation of tumor size for
      MFMC carcinoma.

PMID- 24438066
TI  - Effect of preoperative MRI on mastectomy and contralateral prophylactic
      mastectomy rates at a community hospital by a single surgeon.
AB  - Magnetic resonance imaging (MRI) use in the preoperative evaluation of newly
      diagnosed breast cancer (BC) patients is rising. We evaluated MRI as a function
      of surgical year with respect to mastectomy and contralateral prophylactic
      mastectomy (CPM) rates by a single surgeon. From January 2000 to December 2010,
      1,279 patients with 1,296 breast cancers were identified. Our breast MRI was
      installed in April 2006. Mastectomy and CPM rates were evaluated by surgical year
      and stratified as "pre-MRI" or "MRI" depending on whether surgery occurred before
      or after April 2006. There was a significant increase in the percentage of
      patients undergoing MRI in the "pre-MRI" versus "MRI" era (17.2% versus 78.7%, p
      < 0.001). In contrast, mastectomy rates decreased with 29.9% undergoing
      mastectomy before 2006 versus 24.5% after 2006 (p = 0.038). Except for 2007,
      where CPM rates dropped to 7.1%, CPM rates increased from 16.7% in 2000 to 51.9%
      in 2010 (p = 0.033). The use of MRI, additional MRI findings and additional MRI
      biopsies were not associated with the decision for CPM. Age <50 was the only
      factor associated with CPM (RR = 2.12, p = 0.001). In our community hospital,
      mastectomy rates have decreased despite the increased use of preoperative MRI.
      MRI alone may not explain the increasing rates of mastectomy reported in other
      series. CPM rates have dramatically increased over time, seemingly independent of
      MRI use. Prospective studies are needed to assess the role of surgeon bias, along
      with other factors, in surgical decision making.

PMID- 24438067
TI  - Equity in Ghanaian breast cancer treatment outcomes-a modeling study in Komfo
      Anokye Teaching Hospital.

PMID- 24438068
TI  - Exploring causal networks of bovine milk fatty acids in a multivariate mixed
      model context.
AB  - BACKGROUND: Knowledge regarding causal relationships among traits is important to
      understand complex biological systems. Structural equation models (SEM) can be
      used to quantify the causal relations between traits, which allow prediction of
      outcomes to interventions applied to such a network. Such models are fitted
      conditionally on a causal structure among traits, represented by a directed
      acyclic graph and an Inductive Causation (IC) algorithm can be used to search for
      causal structures. The aim of this study was to explore the space of causal
      structures involving bovine milk fatty acids and to select a network supported by
      data as the structure of a SEM. RESULTS: The IC algorithm adapted to mixed models
      settings was applied to study 14 correlated bovine milk fatty acids, resulting in
      an undirected network. The undirected pathway from C4:0 to C12:0 resembled the de
      novo synthesis pathway of short and medium chain saturated fatty acids. By using
      prior knowledge, directions were assigned to that part of the network and the
      resulting structure was used to fit a SEM that led to structural coefficients
      ranging from 0.85 to 1.05. The deviance information criterion indicated that the
      SEM was more plausible than the multi-trait model. CONCLUSIONS: The IC algorithm
      output pointed towards causal relations between the studied traits. This changed
      the focus from marginal associations between traits to direct relationships, thus
      towards relationships that may result in changes when external interventions are
      applied. The causal structure can give more insight into underlying mechanisms
      and the SEM can predict conditional changes due to such interventions.

PMID- 24438069
TI  - Video Q&A: state-of-the-art therapy for the elite and non-elite athlete: an
      interview with Mike Carmont.
AB  - In this video Q&A, Mr Mike Carmont answers questions about state-of-the-art
      treatments for elite athletes, and the progress and challenges behind translating
      these into successful therapies for the non-elite athlete. 

PMID- 24438070
TI  - Expression levels of insulin receptor substrate-1 modulate the osteoblastic
      differentiation of mesenchymal stem cells and osteosarcoma cells.
AB  - The insulin-like growth factor-1 system, including its critical mediator insulin
      receptor substrate-1 (IRS-1), is involved in regulating osteosarcoma (OS) cell
      proliferation or differentiation. The aim of this study is to define the role of
      IRS-1 in OS cells by assessing the contribution of IRS-1 in the differentiation
      of human and murine OS cell lines and mouse mesenchymal stem cells (MSCs) and
      found that the basal level of IRS-1 is important for the initiation of
      differentiation. Both down-regulation and over-expression of IRS-1 inhibited
      osteoblastic differentiation. In vivo studies showed that OS cells over
      expressing IRS-1 have increased metastatic potential and tumor growth. The
      proteasome inhibitor MG-132 led to an increase in IRS-1 protein level that
      inhibited osteoblastic differentiation, suggesting a role for proteasomal
      regulation in maintaining the appropriate expression level of IRS-1. Thus,
      precise regulation of IRS-1 expression level is critical for determining the
      differentiating capacity of MSCs and OS cells, and that derangement of IRS-1
      levels can be a critical step in OS transformation.

PMID- 24438071
TI  - Ibuprofen inhibits migration and proliferation of human coronary artery smooth
      muscle cells by inducing a differentiated phenotype: role of peroxisome
      proliferator-activated receptor gamma.
AB  - OBJECTIVES: The search for agents that are capable of preventing restenosis and
      reduce the risk of late thrombosis is of utmost importance. In this study we aim
      to evaluate the in vitro effects of ibuprofen on proliferation and migration of
      human coronary artery smooth muscle cells and on endothelial cells. METHODS: Cell
      proliferation was evaluated by trypan blue exclusion. Cell migration was assessed
      by wound-healing 'scratch' assay and time-lapse video microscopy. Protein
      expression was assessed by immunoblotting, and morphology by immunocytochemistry.
      The involvement of the PPARgamma pathway was studied with the agonist
      troglitazone, and the use of selective antagonists such as PGF2alpha and GW9662.
      KEY FINDINGS: We demonstrate that ibuprofen inhibits proliferation and migration
      of HCASMCs and induces a switch in HCASMCs towards a differentiated and
      contractile phenotype, and that these effects are mediated through the PPARgamma
      pathway. Importantly we also show that the effects of ibuprofen are cell type
      specific as it does not affect migration and proliferation of endothelial cells.
      CONCLUSIONS: Taken together, our results suggest that ibuprofen could be an
      effective drug for the development of novel drug-eluting stents that could lead
      to reduced rates of restenosis and potentially other complications of DES
      implantation.

PMID- 24438072
TI  - How is the heart best protected in chronic dialysis patients?: Between Scylla and
      Charybdis: what is the appropriate role for percutaneous coronary
      revascularization and coronary artery bypass grafting in patients on dialysis?

PMID- 24438073
TI  - Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous
      tumor growth and prolongs survival of mice.
AB  - BACKGROUND: Adoptive transfer of T cells genetically engineered with a chimeric
      antigen receptor (CAR) has successfully been used to treat both chronic and acute
      lymphocytic leukemia as well as other hematological cancers. Experimental therapy
      with CAR-engineered T cells has also shown promising results on solid tumors. The
      prostate stem cell antigen (PSCA) is a protein expressed on the surface of
      prostate epithelial cells as well as in primary and metastatic prostate cancer
      cells and therefore a promising target for immunotherapy of prostate cancer.
      METHODS: We developed a third-generation CAR against PSCA including the CD28, OX
      40 and CD3 zeta signaling domains. T cells were transduced with a lentivirus
      encoding the PSCA-CAR and evaluated for cytokine production (paired Student's t
      test), proliferation (paired Student's t-test), CD107a expression (paired
      Student's t-test) and target cell killing in vitro and tumor growth and survival
      in vivo (Log-rank test comparing Kaplan-Meier survival curves). RESULTS: PSCA-CAR
      T cells exhibit specific interferon (IFN)-gamma and interleukin (IL)-2 secretion
      and specific proliferation in response to PSCA-expressing target cells.
      Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing
      tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells
      significantly delays subcutaneous tumor growth and prolongs survival of mice.
      CONCLUSIONS: Our data confirms that PSCA-CAR T cells may be developed for
      treatment of prostate cancer.

PMID- 24438074
TI  - Size of cup affects the anterior capsular distance in total hip arthroplasty, as
      measured with ultrasound.
AB  - BACKGROUND: Previously was found that sonography is a reliable method to measure
      a capsular distance in total hip arthroplasty hips. The aim of our current study
      was to investigate the relation between the implanted size of the cup and the
      anterior capsular distance, as measured with ultrasound one year after THA.
      METHODS: 50 osteoarthritis (OA) patients operated on with total hip arthroplasty
      one year before were included in the study and the anterior capsular distance was
      measured sonographically. Patients were grouped with respect to cup size. The
      correlation between the implanted cup size and capsular distance was determined.
      RESULTS: The mean capsular distance in the whole group was 1.37 (SD 0.19) cm. The
      mean capsular distance in the group with small cups was 1.27 (SD 0.13) cm, in
      large cups it was 1.45 (SD 0.20) cm, p = 0.02. Spearman correlation analysis
      showed a statistically significant correlation between a greater capsular
      distance and the larger size of the cup (r = 0.5, p < 0.0001). CONCLUSION: The
      greater capsular distance in successful THA hips is affected by cup size. We
      propose that this should be considered when evaluating sonography of the anterior
      capsular distance after THA.

PMID- 24438076
TI  - Niemann-Pick disease type C2 protein induces triglyceride accumulation in
      silkworm and mammalian cell lines.
AB  - Silkworm haemolymph induced both the cessation of growth and an increase in
      triglyceride (triacylglycerol) storage in BmN4 cells. We purified the growth
      inhibitory factor from the silkworm haemolymph and identified this protein as the
      Bombyx mori PP (promoting protein), an orthologue of NPC2 (Niemann-Pick disease
      type C2) protein. Recombinant silkworm NPC2 inhibited cellular proliferation and
      increased triglyceride accumulation in BmN4 cells. Injection of either the
      recombinant protein or antiserum of NPC2 into living silkworms increased or
      decreased respectively triglyceride levels in the fat body. A mutation that
      depletes the cholesterol-binding capacity did not abolish the activity of NPC2.
      We further revealed that NPC2 induced the phosphorylation of AMPK (AMP-activated
      protein kinase) and that an AMPK inhibitor suppressed NPC2-dependent triglyceride
      accumulation. These findings suggest that NPC2 induces triglyceride accumulation
      via the activation of AMPK independently of its cholesterol-binding capacity in
      the silkworm.

PMID- 24438075
TI  - Plus ca change - evolutionary sequence divergence predicts protein subcellular
      localization signals.
AB  - BACKGROUND: Protein subcellular localization is a central problem in
      understanding cell biology and has been the focus of intense research. In order
      to predict localization from amino acid sequence a myriad of features have been
      tried: including amino acid composition, sequence similarity, the presence of
      certain motifs or domains, and many others. Surprisingly, sequence conservation
      of sorting motifs has not yet been employed, despite its extensive use for tasks
      such as the prediction of transcription factor binding sites. RESULTS: Here, we
      flip the problem around, and present a proof of concept for the idea that the
      lack of sequence conservation can be a novel feature for localization prediction.
      We show that for yeast, mammal and plant datasets, evolutionary sequence
      divergence alone has significant power to identify sequences with N-terminal
      sorting sequences. Moreover sequence divergence is nearly as effective when
      computed on automatically defined ortholog sets as on hand curated ones.
      Unfortunately, sequence divergence did not necessarily increase classification
      performance when combined with some traditional sequence features such as amino
      acid composition. However a post-hoc analysis of the proteins in which sequence
      divergence changes the prediction yielded some proteins with atypical (i.e. not
      MPP-cleaved) matrix targeting signals as well as a few misannotations.
      CONCLUSION: We report the results of the first quantitative study of the
      effectiveness of evolutionary sequence divergence as a feature for protein
      subcellular localization prediction. We show that divergence is indeed useful for
      prediction, but it is not trivial to improve overall accuracy simply by adding
      this feature to classical sequence features. Nevertheless we argue that sequence
      divergence is a promising feature and show anecdotal examples in which it
      succeeds where other features fail.

PMID- 24438077
TI  - Effect of electric toothbrush on residents' oral hygiene: a randomized clinical
      trial in nursing homes.
AB  - A single-blinded, randomized controlled clinical trial was performed to
      investigate the effect of electric toothbrushes (ET) compared with manual
      toothbrushes (MT) on residents in nursing homes and to evaluate the caregiver's
      opinion on ET. A sample of 180 nursing-home residents were given either a new ET
      or a new MT. Oral examinations were performed to measure dental hygiene, using
      the Oral Hygiene Index-Simplified (OHI-S). Both groups received the same
      instructions for use. After 2 months participants were re-examined.
      Questionnaires were then sent to their caregivers. Participants' mean age was
      86.1 +/- 7.7 yr, and the mean number of remaining teeth was 20 +/- 5.6. No
      specific intervention effect was found for ET. Both groups showed identical
      improvements in the OHI-S, from 1.27 +/- 0.63 at baseline (the mean value for all
      participants) to 1.01 +/- 0.53 after 2 months. Of 152 caregivers who responded to
      the questionnaire, the majority evaluated ET to be beneficial and less time
      consuming compared with MT, also for demented residents. In a frail population,
      no difference is found in the effect of ET compared with MT. However, the ET
      appears to be a useful aid for residents who receive assistance with dental
      hygiene.

PMID- 24438078
TI  - Prognostic value of surgical margin status in gastric cancer patients.
AB  - BACKGROUND: It has been reported that positive surgical margin is one of the most
      significant risk factors for local recurrence and poor survival. However, the
      survival of gastric cancer (GC) patients with positive margin is still
      controversial. METHODS: A total of 1025 stage I-III GC patients who underwent
      gastrectomy with curative intent between January 2003 and April 2008 in our
      centre were enrolled in this study, of whom, 75 patients got a microscopic
      positive resection margin. Other 950 patients with negative resection margin were
      used for comparison. RESULTS: Borrmann type and extranodal metastasis were
      independent risk factors for positive margin. The 5-year overall survival for the
      patients with positive margin is merely 13.3%. Survival in such patients was
      similar to that of the patients staged IIIc with R0 resection. In multivariate
      analysis, surgical margin status was found to be an independent prognostic factor
      for GC patients, while histology, tumour location, TNM stage and chemotherapy
      were independently associated with overall survival for patients with positive
      margin. CONCLUSION: Surgical margin status is an independent prognostic factor
      for GC. Patients with positive margin have a poor prognosis, similar to that of
      IIIc stage disease. When the tumour demonstrates infiltrative growth pattern
      (Borrmann type III and IV) and the surgical margin status is difficult to
      determine, extended gastrectomy should be implemented to ensure an R0 resection.
      Those high-risk patients should be considered for postoperative chemotherapy.

PMID- 24438079
TI  - An accelerated mouse model for atherosclerosis and adipose tissue inflammation.
AB  - BACKGROUND: Obesity and particularly the metabolic syndrome, which is often
      associated with obesity, combine a major risk for type 2 diabetes and
      cardiovascular disease. Emerging evidence indicate obesity-associated subclinical
      inflammation primarily originating from adipose tissue as a common cause for type
      2 diabetes and cardiovascular disease. However, a suitable and well-characterized
      mouse model to simultaneously study obesity-associated metabolic disorders and
      atherosclerosis is not available yet. Here we established and characterized a
      murine model combining diet-induced obesity and associated adipose tissue
      inflammation and metabolic deteriorations as well as atherosclerosis, hence
      reflecting the human situation of cardio-metabolic disease. METHODS: We compared
      a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose
      diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR-/-) mice.
      Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic
      lipid accumulation, and inflammatory gene expression in adipose tissue and liver
      were assessed. RESULTS: After 12-16 weeks, LDLR-/- mice fed HFSC or HFC developed
      significant diet-induced obesity, adipose tissue inflammation, insulin
      resistance, and impaired glucose tolerance compared to lean controls. Notably,
      HFSC-fed mice developed significantly higher adipose tissue inflammation in
      parallel with significantly elevated atherosclerotic lesion area compared to
      those on HFC. Moreover, LDLR-/- mice on HFSC showed increased insulin resistance
      and impaired glucose tolerance relative to those on HFC. After prolonged feeding
      (20 weeks), however, no significant differences in inflammatory and metabolic
      parameters as well as atherosclerotic lesion formation were detectable any more
      between LDLR-/- mice fed HFSC or HFC. CONCLUSION: The use of high sucrose rather
      than more complex carbohydrates in high-fat diets significantly accelerates
      development of obesity-driven metabolic complications and atherosclerotic plaque
      formation parallel to obesity-induced adipose tissue inflammation in LDLR-/-
      mice. Hence LDLR-/- mice fed high-fat high-sucrose cholesterol-enriched diet
      appear to be a suitable and time-saving animal model for cardio-metabolic
      disease. Moreover our results support the suggested interrelation between adipose
      tissue inflammation and atherosclerotic plaque formation.

PMID- 24438080
TI  - Autologous stem cell transplantation for follicular lymphoma is of most benefit
      early in the disease course and can result in durable remissions, irrespective of
      prior rituximab exposure.
AB  - The role of autologous stem cell transplantation (ASCT) and the optimal timing of
      such transplants in patients with follicular lymphoma (FL) remains contentious.
      We present a single-centre experience documenting the outcomes of 70 FL patients
      who underwent BEAM (carmustine, cytarabine, etopside, melphalan)-conditioned ASCT
      between 1988 and 2009. With a median follow-up of 6.8 years (0.1-19.2), the 7
      year overall survival (OS) and progression-free survival (PFS) from the date of
      ASCT was 76% and 60%, respectively. A significant difference in OS was found when
      comparing the patients transplanted in first or second remission versus those
      transplanted in later remissions (P = 0.02) and this significance was maintained
      when OS was calculated from the date of diagnosis (P = 0.03). There was a plateau
      on the PFS curves for patients transplanted in either first or second remissions
      after 9.3 and 6.4 years respectively, suggesting that these groups may never
      relapse. No differences were seen in OS or PFS in those treated with rituximab
      prior to transplant versus those who were not. Our data shows that BEAM ASCT can
      be a highly effective treatment in patients with FL early in the disease course,
      and that a proportion of patients experience prolonged disease-free survival and
      may be cured.

PMID- 24438081
TI  - Self-centering, split-tip catheter has better patency than symmetric-tip tunneled
      hemodialysis catheter: single-center retrospective analysis.
AB  - The performance and safety of a new self-centering, split-tip hemodialysis
      tunneled catheter was compared with a symmetric-tip catheter. The new catheter
      has a greater separation between the arterial and venous tips, with dual
      apertures designed to permanently face the center of the blood vessel. The design
      is intended to improve dialysis efficiency by increasing flow rates while
      decreasing recirculation, fibrin sheath formation, thrombosis, and vessel wall
      occlusions. The study results indicated that the self-centering, split-tip
      catheter had statistically greater patency after 3 months with similar clearance,
      blood flow, and safety. 

PMID- 24438082
TI  - Modulation of Na+/H+ exchanger 3 trafficking and activity in rat proximal tubule.

PMID- 24438083
TI  - Functional characterization of c-Mpl ectodomain mutations that underlie
      congenital amegakaryocytic thrombocytopenia.
AB  - Activation of the cell surface receptor, c-Mpl, by the cytokine, thrombopoietin
      (TPO), underpins megakaryocyte and platelet production in mammals. In humans,
      mutations in c-Mpl have been identified as the molecular basis of Congenital
      Amegakaryocytic Thrombocytopenia (CAMT). Here, we show that CAMT-associated
      mutations in c-Mpl principally lead to defective receptor presentation on the
      cell surface. In contrast, one CAMT mutant c-Mpl, F104S, was expressed on the
      cell surface, but showed defective TPO binding and receptor activation. Using
      mutational analyses, we examined which residues adjacent to F104 within the
      membrane-distal cytokine receptor homology module (CRM) of c-Mpl comprise the TPO
      binding epitope, revealing residues within the predicted Domain 1 E-F and A-B
      loops and Domain 2 F'-G' loop as key TPO-binding determinants. These studies
      underscore the importance of the c-Mpl membrane-distal CRM to TPO-binding and
      suggest that mutations within this CRM that perturb TPO binding could give rise
      to CAMT.

PMID- 24438084
TI  - A model of hematopoietic stem cell proliferation under the influence of a
      chemotherapeutic agent in combination with a hematopoietic inducing agent.
AB  - BACKGROUND: Hematopoiesis is a complex process that encompasses both pro-mitotic
      and anti-mitotic stimuli. Pharmacological agents used in chemotherapy have a
      prominent anti-mitotic effect. The approach of inhibiting cell proliferation is
      rational with respect to the rapidly dividing malignant cells. However, it poses
      a serious problem with respect to cell proliferation of cell types required for
      the 'house-keeping' operations of the human body. One such affected system is
      hematopoiesis. Chemotherapy induced anemia is an undesired side effect of
      chemotherapy that can lead to serious complications. Patients exhibiting anemia
      or leukopenia during chemotherapy are frequently administered a hematopoietic
      inducing agent that enhances hematopoiesis. METHODS: In previous work, we derived
      a mathematical model consisting of a set of delay differential equations that was
      dependent on the effect of a hematopoietic inducing agent. The aim of the current
      work was to formulate a mathematical model that captures both the effect of a
      chemotherapeutic agent in combination with a hematopoietic inducing agent. Steady
      state solutions and stability analysis of the system of equations is performed
      and numerical simulations of the stem cell population are provided. RESULTS:
      Numerical simulations confirm that our mathematical model captures the desired
      result which is that the use of hematopoietic agents in conjunction with
      chemotherapeutic agents can decrease the negative secondary effects often
      experienced by patients. CONCLUSIONS: The proposed model indicates that the
      introduction of hematopoietic inducing agents have clinical potential to offset
      the deleterious effects of chemotherapy treatment. Furthermore, the proposed
      model is relevant in that it enhances the understanding of stem cell dynamics and
      provides insight on the stem cell kinetics.

PMID- 24438085
TI  - Migrated abandoned epicardial pacing wire resulting in a breast abscess.

PMID- 24438086
TI  - Unilateral instrumented fixation for cervical dumbbell tumors.
AB  - PURPOSE: The purpose of this study was to describe the radiological outcomes in
      patients with unilateral instrumented fixation for cervical dumbbell tumors.
      PATIENTS AND METHODS: Fourteen consecutive individuals were included in the
      present study. We included Eden type II and III tumors in this cohort study and
      analyzed fixed segment fusion rates, screw failure with multiplanar
      reconstruction computed tomography (CT) scan radiographs and lateral radiographs
      with flexion-extension dynamic views, and immediate postoperative and last follow
      up radiographs after surgery. RESULTS: The mean follow-up was 105.4 months. There
      were six men and eight women ranging in age from 32 to 70 years (mean age, 48
      years). Twenty pedicle screws (PSs) and 11 lateral mass screws (LMSs) were used
      in total. There were seven patients with only PSs, four with only LMSs, and three
      with PSs at C2 and LMSs at C3. PS misplacement occurred in three screws of
      insertions including two screws with grade 1 misplacement and one screw with
      grade 2 misplacement, and no grade 3 misplacement occurred. All screws breached
      the lateral wall with no apparent superior or inferior misplacement. None of the
      LMSs were misplaced. Fortunately, no complication could be directly attributed to
      screw insertion. Radiological evidence showed that all patients achieved
      successful fusion with no screw loosening or breakage. However, two patients who
      received only LMS fixation had degenerative spondylolisthesis at the upper fusion
      segment at the last follow-up. CONCLUSIONS: Grade 2 PS misplacement occurred in
      one screw of insertions. Unilateral pedicle screw fixation for cervical dumbbell
      tumors is a useful surgical method that can successfully fuse vertebrae with good
      postoperative alignment.

PMID- 24438087
TI  - Aridity shapes cyanogenesis cline evolution in white clover (Trifolium repens
      L.).
AB  - Adaptive differentiation between populations is often proposed to be the product
      of multiple interacting selective pressures, although empirical support for this
      is scarce. In white clover, populations show adaptive differentiation in
      frequencies of cyanogenesis, the ability to produce hydrogen cyanide after tissue
      damage. This polymorphism arises through independently segregating polymorphisms
      for the presence/absence of two required cyanogenic components, cyanogenic
      glucosides and their hydrolysing enzyme. White clover populations worldwide have
      evolved a series of recurrent, climate-associated clines, with higher frequencies
      of cyanogenic plants in warmer locations. These clines have traditionally been
      hypothesized to reflect a fitness trade-off between chemical defence in herbivore
      rich areas (warmer climates) and energetic costs of producing cyanogenic
      components in areas of low herbivore pressure (cooler climates). Recent
      observational studies suggest that cyanogenic components may also be beneficial
      in water-stressed environments. We investigated fitness trade-offs associated
      with temperature-induced water stress in the cyanogenesis system using
      manipulative experiments in growth chambers and population surveys across a
      longitudinal precipitation gradient in the central United States. We find that
      plants producing cyanogenic glucosides have higher relative fitness in treatments
      simulating a moderate, persistent drought stress. In water-neutral treatments,
      there are energetic costs to producing cyanogenic components, but only in
      treatments with nutrient stress. These fitness trade-offs are consistent with
      cyanogenesis frequencies in natural populations, where we find clinal variation
      in the proportion of plants producing cyanogenic glucosides along the
      precipitation gradient. These results suggest that multiple selective pressures
      interact to maintain this adaptive polymorphism and that modelling adaptation
      will require knowledge of environment-specific fitness effects. 

PMID- 24438088
TI  - The novel IGF-IR/Akt-dependent anticancer activities of glucosamine.
AB  - BACKGROUND: Recent studies have shown that glucosamine inhibits the proliferation
      of various human cancer cell lines and downregulates the activity of COX-2, HIF
      1alpha, p70S6K, and transglutaminase 2. Because the IGF-1R/Akt pathway is a
      common upstream regulator of p70S6K, HIF-1alpha, and COX-2, we hypothesized that
      glucosamine inhibits cancer cell proliferation through this pathway. METHODS: We
      used various in vitro assays including flow cytometry assays, small interfering
      RNA (siRNA) transfection, western blot analysis, MTT (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) assays, reverse transcription-polymerase
      chain reaction, and in vivo xenograft mouse model to confirm anticancer
      activities of glucosamine and to investigate the molecular mechanism. RESULTS: We
      found that glucosamine inhibited the growth of human non-small cell lung cancer
      (NSCLC) cells and negatively regulated the expression of IGF-1R and
      phosphorylation of Akt. Glucosamine decreased the stability of IGF-1R and induced
      its proteasomal degradation by increasing the levels of abnormal glycosylation on
      IGF-1R. Moreover, picropodophyllin, a selective inhibitor of IGF-1R, and the IGF
      1R blocking antibody IMC-A12 induced significant cell growth inhibition in
      glucosamine-sensitive, but not glucosamine-resistant cell lines. Using in vivo
      xenograft model, we confirmed that glucosamine prohibits primary tumor growth
      through reducing IGF-1R signalling and increasing ER-stress. CONCLUSIONS: Taken
      together, our results suggest that targeting the IGF-1R/Akt pathway with
      glucosamine may be an effective therapeutic strategy for treating some type of
      cancer.

PMID- 24438089
TI  - Development of loop-mediated isothermal amplification assay for specific and
      rapid detection of differential goat pox virus and sheep pox virus.
AB  - BACKGROUND: Capripox viruses are economically important pathogens in goat and
      sheep producing areas of the world, with specific focus on goat pox virus (GTPV),
      sheep pox virus (SPPV) and the Lumpy Skin Disease virus (LSDV). Clinically, sheep
      pox and goat pox have the same symptoms and cannot be distinguished
      serologically. This presents a real need for a rapid, inexpensive, and easy to
      operate and maintain genotyping tool to facilitate accurate disease diagnosis and
      surveillance for better management of Capripox outbreaks. RESULTS: A LAMP method
      was developed for the specific differential detection of GTPV and SPPV using
      three sets of LAMP primers designed on the basis of ITR sequences. Reactions were
      performed at 62 degrees C for either 45 or 60 min, and specificity confirmed by
      successful differential detection of several GTPV and SPPV isolates. No cross
      reactivity with Orf virus, foot-and-mouth disease virus (FMDV), A. marginale
      Lushi isolate, Mycoplasma mycoides subsp. capri, Chlamydophila psittaci,
      Theileria ovis, T. luwenshuni, T. uilenbergi or Babesia sp was noted. RFLP-PCR
      analysis of 135 preserved epidemic materials revealed 48 samples infected with
      goat pox and 87 infected with sheep pox, with LAMP test results showing a
      positive detection for all samples. When utilizing GTPV and SPPV genomic DNA, the
      universal LAMP primers (GSPV) and GTPV LAMP primers displayed a 100% detection
      rate; while the SPPV LAMP detection rate was 98.8%, consistent with the
      laboratory tested results. CONCLUSIONS: In summary, the three sets of LAMP
      primers when combined provide an analytically robust method able to fully
      distinguish between GTPV and SPPV. The presented LAMP method provides a specific,
      sensitive and rapid diagnostic tool for the distinction of GTPV and SPPV
      infections, with the potential to be standardized as a detection method for
      Capripox viruses in endemic areas.

PMID- 24438090
TI  - Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone
      for stage IV rectal cancer.
AB  - BACKGROUND: Complete pathological response occurs in 10-20% of patients with
      rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to
      pelvic surgery. The possibility that complete pathological response of rectal
      cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is
      an intriguing hypothesis. CASE PRESENTATION: A 66-year old man presented an
      adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included
      in a reverse treatment, aiming at first downsizing the liver metastases by
      chemotherapy, and subsequently performing the liver surgery prior to the rectum
      resection. The neoadjuvant chemotherapy consisted in a combination of
      oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right
      portal embolization, an extended right liver lobectomy was performed. On the
      final histopathological analysis, all lesions were fibrotic, devoid of any viable
      cancer cells. One month after liver surgery, the rectoscopic examination showed a
      near-total response of the primary rectal adenocarcinoma, which convinced the
      colorectal surgeon to perform the low anterior resection without preoperative
      radiation therapy. Macroscopically, a fibrous scar was observed at the level of
      the previously documented tumour, and the histological examination of the
      surgical specimen did not reveal any malignant cells in the rectal wall as well
      as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the
      final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient
      is currently alive 5 years after the first surgery without evidence of
      recurrence. CONCLUSION: The presented patient with stage IV rectal cancer and
      liver metastases was in a unique situation linked to its inclusion in a reversed
      treatment and the use of neoadjuvant chemotherapy alone. The observed achievement
      of a complete pathological response after chemotherapy should promote the design
      of prospective randomized studies to evaluate the benefits of chemotherapy alone
      in patients with stages II-III rectal adenocarcinoma (without metastasis).

PMID- 24438092
TI  - Treatment of frontal fibrosing alopecia and lichen planopilaris.

PMID- 24438091
TI  - Monitoring progress toward measles elimination by genetic diversity analysis of
      measles viruses in China 2009-2010.
AB  - With the achievement of high coverage for routine immunization and supplementary
      immunization activities (SIAs), measles incidence in mainland China reached its
      lowest level in 2010. The proportion of measles cases in the vaccination-targeted
      population decreased during 2007-2010 after the SIAs. More than 60% of measles
      cases were in adults or infants, especially in the coastal and eastern provinces
      during 2009 and 2010. A total 567 isolates of measles virus were obtained from
      clinical specimens from 27 of 31 provinces in mainland China during 2009 and
      2010. Except for two vaccine-associated cases, one genotype D4 strain, two
      genotype D9 strains, and four genotype D11 strains, the other 558 strains were
      genotype H1 cluster H1a. Genotype H1 has been the only endemic genotype detected
      in China since surveillance began in 1993. Only genotype H1 was found in mainland
      China during 1993-2008, except for one detection of genotype H2. More recently,
      multiple genotypes of imported measles were detected even with the background of
      endemic genetotype H1 viruses. Analysis of the 450-nucleotide sequencing window
      of the measles virus N gene showed that the overall genetic diversity of the
      recent geneotype H1 strains decreased between 2008 and 2010. The lower genetic
      diversity of H1 strains suggested that enhanced vaccination may have reduced the
      co-circulating lineages of endemic genotype H1 strains in mainland China.

PMID- 24438093
TI  - CREB phosphorylation at Ser133 regulates transcription via distinct mechanisms
      downstream of cAMP and MAPK signalling.
AB  - CREB (cAMP-response-element-binding protein) is an important transcription factor
      for the activation of a number of immediate early genes. CREB is phosphorylated
      on Ser133 by PKA (protein kinase A), promoting the recruitment of the co
      activator proteins CBP (CREB-binding protein) and p300; this has been proposed to
      increase the transcription of CREB-dependent genes. CREB is also phosphorylated
      on Ser133 by MSK1/2 (mitogen- and stress-activated kinase 1/2) in cells in
      response to the activation of MAPK (mitogen-activated protein kinase) signalling;
      however, the relevance of this to gene transcription has been controversial. To
      resolve this problem, we created a mouse with a Ser133 to alanine residue
      mutation in the endogenous Creb gene. Unlike the total CREB knockout, which is
      perinatally lethal, these mice were viable, but born at less than the expected
      Mendelian frequency on a C57Bl/6 background. Using embryonic fibroblasts from the
      S133A-knockin mice we show in the present study that Ser133 phosphorylation
      downstream of PKA is required for CBP/p300 recruitment. The requirement of Ser133
      phosphorylation for the PKA-mediated induction of CREB-dependent genes was,
      however, promoter-specific. Furthermore, we show that in cells the
      phosphorylation of CREB on Ser133 by MSKs does not promote strong recruitment of
      CBP or p300. Despite this, MSK-mediated CREB phosphorylation is critical for the
      induction of CREB-dependent genes downstream of MAPK signalling. 

PMID- 24438095
TI  - Measurement of thyroxine and cortisol in canine and feline blood samples using
      two immunoassay analysers.
AB  - OBJECTIVES: The AIA-360 (Tosoh Corporation) is an automated immunoassay analyser.
      The aims of this study were to estimate the precision of thyroxine and cortisol
      AIA-360 immunoassays in canine and feline samples and to compare the results
      produced with those obtained by a chemiluminescence analyser (Immulite(r) 1000,
      Siemens). METHODS: Blood samples from 240 clinical cases (60 dogs and 60 cats for
      both thyroxine and cortisol) were analysed using both instruments. RESULTS:
      Deming regression calculations showed excellent correlation (thyroxine, canine rs
      = 0 . 94, feline rs  = 0 . 97; cortisol, canine rs  = 0 . 97, feline rs  = 0 .
      97). Agreement between the two instruments was examined by Bland-Altman
      difference plots, which identified wide confidence intervals and outliers for
      thyroxine (canine n = 6, feline n = 4) and cortisol (canine n = 3, feline n = 4)
      results. Inter/intra-run precision of the AIA-360 was excellent for both cortisol
      and thyroxine (coefficients of variation <7%). CLINICAL SIGNIFICANCE: The
      instrument showed excellent correlation for cortisol and thyroxine in canine and
      feline samples demonstrating that the AIA-360 can be used in clinical practice.
      The agreement studies suggest that the results from the AIA-360 cannot be used
      interchangeably with those generated by the Immulite 1000 and should be
      interpreted using reference intervals that have been established specific to the
      AIA-360.

PMID- 24438094
TI  - Preserved function and reduced angiogenesis potential of the quadriceps in
      patients with mild COPD.
AB  - BACKGROUND: Little is known about limb muscle abnormalities in mild COPD.
      Inactivity and systemic inflammation could play a role in the development of limb
      muscle dysfunction in COPD. The objective of the present study was to
      characterize quadriceps function, enzymatic activities and morphometry, levels of
      plasma inflammatory markers and physical activity levels in daily life (PAdl) in
      patients with mild COPD (GOLD 1). METHODS: Mid-thigh muscle cross-sectional area
      (MTCSA), quadriceps strength, endurance, fiber-type distribution, capillarity,
      pro-angiogenesis factors (VEGF-A, angiopoietin I and II) and muscle oxidative
      capacity were assessed in 37 patients with mild COPD and 19 controls. Systemic
      inflammatory markers (CRP, IL-6, TNF-alpha, Fibrinogen, SP-D) and PAdl were
      assessed. RESULTS: MTCSA, quadriceps strength and endurance were not different
      between COPD and controls. Capillarity and muscle oxidative capacity were all
      preserved in mild COPD. Reduced pro-angiogenesis factor mRNA expression was seen
      in COPD. The level of moderately active intensity (>3 METs) was significantly
      lower in mild COPD and, in multiple regression analyses, the level of physical
      activity was a determinant of muscle oxidative capacity and capillarization. No
      between-group differences were found regarding muscle oxidative stress while
      circulating IL-6 levels were elevated in mild COPD. CONCLUSIONS: The quadriceps
      muscle function was preserved in mild COPD although a reduced potential for
      angiogenesis was found. The reduced level of daily activities and evidence of
      systemic inflammation in these individuals suggest that these factors precede the
      development of overt limb muscle dysfunction in COPD.

PMID- 24438096
TI  - End-of-life care and preferences for place of death among the oldest old: results
      of a population-based survey using VOICES-Short Form.
AB  - BACKGROUND: End-of-life care (EOLC) is a key component in care of older people.
      However, evidence suggests that the oldest old (>85 years) are less likely to
      access specialist EOLC. OBJECTIVE: The study's objective was to explore
      experiences of EOLC among the oldest old and determine their reported preference
      for place of death. DESIGN: The study involved a self-completion postbereavement
      survey. METHODS: A census was taken of deaths registered between October 2009 and
      April 2010 in two health districts, identified from death certificates. Views of
      Informal Carers-Evalution of Service (VOICES)-Short Form was sent to each
      informant (n=1422, usually bereaved relative) 6 to 12 months after the death.
      RESULTS: Of 473 (33%) who responded, 48% of decedents were age 85 or over. There
      were no age differences in reported care quality in the last three months, but in
      the last two days the oldest old were reported to receive poorer relief of
      nonpain symptoms and less emotional and spiritual support. Compared to people
      under age 85, the over 85s were less likely to be reported to know they were
      dying, to have a record of their preferences for place of death, to die in their
      preferred place, to have enough choice about place of death-and more likely to be
      reported to have had unwanted treatment decisions. Being over 85 years was
      associated with a reduction in the odds of home death (OR=0.36); failure to
      ascertain and record preference for place of death contributed to this.
      CONCLUSIONS: Age-associated disparity exists in care provided in the last two
      days and the realization of preferences.

PMID- 24438097
TI  - Polio survivors' perceptions of the meaning of quality of life and strategies
      used to promote participation in everyday activities.
AB  - INTRODUCTION: The term 'post-polio syndrome' (PPS) is used to describe new and
      late manifestations of poliomyelitis that occur later in life. Research in this
      area has focused upon health status rather than its effect on quality of life.
      AIM: To gain an in-depth understanding of the meaning of quality of life for
      polio survivors and to determine the type of strategies that are used by people
      with PPS and the support that they consider as important to facilitate
      participation in everyday life activities that have an impact on their quality of
      life. METHOD: Six focus groups were conducted with 51 participants from two
      regions in England. Data were audio-taped and analysed using thematic analysis.
      RESULTS: Our research found that polio survivors used terms used to describe
      quality of life which could be associated with that of happiness. Our research
      has identified resolvable factors that influence quality of life namely
      inaccessible environments, attitudes of health-care professionals and societal
      attitudes. Polio survivors have tried alternative therapies, chiefly acupuncture
      and massage, and found them to be effective in enhancing their quality of life.
      CONCLUSION: It is suggested that health-care professionals should consider
      factors which influence happiness and implement a person-centred approach with
      the views of the polio survivor being listened to. The three factors that
      influenced quality of life could be resolved by health-care professionals and by
      society. With regard to strategies used, we suggest that polio survivors should
      have access to the treatments that they perceive as important, although further
      research is required to design optimal interventions for this client group.

PMID- 24438099
TI  - Motor learning in children with hemiplegic cerebral palsy: feedback effects on
      skill acquisition.
AB  - AIM: Motor learning is enhanced with practice and feedback. This cohort control
      study investigated the effect of different relative feedback frequencies during
      skill acquisition in children with cerebral palsy (CP) and children with typical
      development. METHOD: Nineteen children with spastic hemiplegic CP (nine males, 10
      females; mean age 11 y 7 mo; range 8-16 y) and 20 children with typical
      development (12 males, eight females; mean age 10 y 8 mo; range 8-14 y) were
      assigned to 100% or reduced (62%) feedback subgroups as they practised 200 trials
      of a discrete arm movement with specific spatiotemporal parameters. Children with
      CP used their less involved hand. Learning was inferred by delayed (24 h)
      retention and reacquisition tests. RESULTS: All children improved in accuracy and
      consistency. Children with typical development demonstrated significantly greater
      accuracy than children with CP during acquisition (p=0.001), retention (p=0.031),
      and reacquisition (p=0.001), and greater consistency during retention (p=0.038).
      The typically developing group who received 100% feedback performed with
      significantly less error than the 62% feedback group during acquisition
      (p=0.001), and with greater retention (p=0.017). No statistically significant
      difference was found between feedback subgroups of children with CP, although the
      100% feedback group consistently demonstrated less error. INTERPRETATION:
      Children with CP use feedback in a manner similar to children with typical
      development when learning new skills with their less involved hand, but
      demonstrate less accuracy and consistency.

PMID- 24438098
TI  - Pseudomonas aeruginosa homoserine lactone triggers apoptosis and Bak/Bax
      independent release of mitochondrial cytochrome C in fibroblasts.
AB  - Pseudomonas aeruginosa use N-(3-oxododecanoyl)-homoserine lactone (C12) as a
      quorum-sensing molecule to regulate gene expression in the bacteria. It is
      expected that in patients with chronic infections with P. aeruginosa, especially
      as biofilms, local [C12] will be high and, since C12 is lipid soluble, diffuse
      from the airways into the epithelium and underlying fibroblasts, capillary
      endothelia and white blood cells. Previous work showed that C12 has multiple
      effects in human host cells, including activation of apoptosis. The present work
      tested the involvement of Bak and Bax in C12-triggered apoptosis in mouse embryo
      fibroblasts (MEF) by comparing MEF isolated from embryos of wild-type (WT) and
      Bax(-/-) /Bak(-/-) (DKO) mice. In WT MEF C12 rapidly triggered (minutes to 2 h):
      activation of caspases 3/7 and 8, depolarization of mitochondrial membrane
      potential (Deltapsimito ), release of cytochrome C from mitochondria into the
      cytosol, blebbing of plasma membranes, shrinkage/condensation of cells and nuclei
      and, subsequently, cell killing. A DKO MEF line that was relatively unaffected by
      the Bak/Bax-dependent proapoptotic stimulants staurosporine and etoposide
      responded to C12 similarly to WT MEF: activation of caspase 3/7, depolarization
      of Deltapsimito and release of cytochrome C and cell death. Re-expression of Bax
      or Bak in DKO MEF did not alter the WT-like responses to C12 in DKO MEF. These
      data showed that C12 triggers novel, rapid proapoptotic Bak/Bax-independent
      responses that include events commonly associated with activation of both the
      intrinsic pathway (depolarization of Deltapsimito and release of cytochrome C
      from mitochondria into the cytosol) and the extrinsic pathway (activation of
      caspase 8). Unlike the proapoptotic agonists staurosporine and etoposide that
      release cytochrome C from mitochondria, C12's effects do not require
      participation of either Bak or Bax. 

PMID- 24438100
TI  - Expression of the Aspergillus terreus itaconic acid biosynthesis cluster in
      Aspergillus niger.
AB  - BACKGROUND: Aspergillus terreus is a natural producer of itaconic acid and is
      currently used to produce itaconic acid on an industrial scale. The metabolic
      process for itaconic acid biosynthesis is very similar to the production of
      citric acid in Aspergillus niger. However, a key enzyme in A. niger, cis
      aconitate decarboxylase, is missing. The introduction of the A. terreus cadA gene
      in A. niger exploits the high level of citric acid production (over 200 g per
      liter) and theoretically can lead to production levels of over 135 g per liter of
      itaconic acid in A. niger. Given the potential for higher production levels in A.
      niger, production of itaconic acid in this host was investigated. RESULTS:
      Expression of Aspergillus terreus cis-aconitate decarboxylase in Aspergillus
      niger resulted in the production of a low concentration (0.05 g/L) of itaconic
      acid. Overexpression of codon-optimized genes for cis-aconitate decarboxylase, a
      mitochondrial transporter and a plasma membrane transporter in an oxaloacetate
      hydrolase and glucose oxidase deficient A. niger strain led to highly increased
      yields and itaconic acid production titers. At these higher production titers,
      the effect of the mitochondrial and plasma membrane transporters was much more
      pronounced, with levels being 5-8 times higher than previously described.
      CONCLUSIONS: Itaconic acid can be produced in A. niger by the introduction of the
      A. terreus cis-aconitate decarboxylase encoding cadA gene. This results in a low
      itaconic acid production level, which can be increased by codon-optimization of
      the cadA gene for A. niger. A second crucial requirement for efficient production
      of itaconic acid is the expression of the A. terreus mttA gene, encoding a
      putative mitochondrial transporter. Expression of this transporter results in a
      twenty-fold increase in the secretion of itaconic acid. Expression of the A.
      terreus itaconic acid cluster consisting of the cadA gene, the mttA gene and the
      mfsA gene results in A. niger strains that produce over twenty five-fold higher
      levels of itaconic acid and show a twenty-fold increase in yield compared to a
      strain expressing only CadA.

PMID- 24438101
TI  - Seventeen-millimeter St. Jude Medical Regent valve in patients with small aortic
      annulus: dose moderate prosthesis-patient mismatch matter?
AB  - BACKGROUND: The study was designed to evaluate the effects of moderate prosthesis
      patient mismatch (defined as 0.65 cm(2)/m(2) <indexed effective orifice area <=
      0.85 cm(2)/m(2)) on midterm outcomes after isolated aortic valve replacement with
      a 17-mm St. Jude Medical Regent valve in a large series of patients, and to
      determine if these effects are influenced by patient confounding variables.
      METHODS: One-hundred and six patients with and without moderate prosthesis
      patient mismatch early after implantation of a 17-mm Regent valve at aortic
      position were included. Both clinical and echocardiographic assessments were
      performed preoperatively, at discharge and during follow-up period (mean follow
      up time 52.6 +/- 11.9 months). RESULTS: The prevalence of moderate prosthesis
      patient mismatch was documented in 46 patients (43.4%) at discharge. During the
      follow-up period, no difference in the regression of left ventricular mass,
      decrease of transvalvular pressure gradients, mortality and prosthesis-related
      complications was observed between patients with and without moderate prosthesis
      patient mismatch. After adjustment for several risk factors, moderate prosthesis
      patient mismatch was associated with increased midterm mortality in patients with
      baseline left ventricular ejection fraction<50% (HR: 1.80, p=0.02), but with
      normal prognosis in those with preserved LV function. Younger age (cut off
      value=65 years) was not an independent predictor of increased midterm mortality
      and valve-related complications in patients with moderate prosthesis-patient
      mismatch. CONCLUSIONS: Moderate prosthesis-patient mismatch after aortic valve
      replacement with a small mechanical prosthesis is associated with increased
      mortality and adverse events in patients with pre-existing left ventricular
      dysfunction. Selected patients with small aortic annulus can experience
      satisfactory clinical improvements and midterm survival after aortic valve
      replacement with a 17-mm Regent valve.

PMID- 24438102
TI  - Renal denervation restores the baroreflex control of renal sympathetic nerve
      activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal
      failure.
AB  - AIM: There is evidence that in chronic renal failure, the sympathetic nervous
      system is activated. This study investigated the role of the renal innervation in
      suppressing high- and low-pressure baroreflex control of renal sympathetic nerve
      activity and heart rate in cisplatin-induced renal failure. METHODS: Renal
      failure was induced using cisplatin (5 mg kg(-1) , i.p.) and the rats used 7 days
      later. Groups of rats were anaesthetized and prepared for measurement of renal
      sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal
      denervation was performed, and renal sympathetic nerve activity and heart rate
      baroreflex gain curves were generated while the cardiopulmonary receptors were
      stimulated using an acute saline volume load. RESULTS: Cisplatin administration
      reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional
      excretions fourfold, plasma creatinine and kidney index by 39 and 30%
      respectively, (all P < 0.05) compared with control rats. In the renal failure
      rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate
      was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control
      animals. Bilateral, but not unilateral, renal denervation restored baroreflex
      sensitivity to normal values. Volume expansion reduced (P < 0.05) renal
      sympathetic nerve activity by 34% in control rats, but remained unchanged in the
      renal failure rats. Unilateral and bilateral renal denervation progressively
      restored the volume expansion induced renal sympathoinhibition to control values.
      CONCLUSION: These findings reveal a significant role of the renal sensory
      innervation in cisplatin-damaged kidneys which blunt the normal baroreflex
      control of renal sympathetic nerve activity.

PMID- 24438104
TI  - Three-dimensional minimally invasive video-assisted thyroidectomy: preliminary
      report.
AB  - Three-dimensional (3D) minimally invasive video-assisted thyroidectomy (MIVAT)
      was carried out with a 4-mm, 3D 0-degree stereoscopic endoscope. The procedure
      was applied on 3 patients who underwent total thyroidectomy and data were
      prospectively collected. Operative time for total thyroidectomy ranged from 72 to
      90 minutes. Neither intra-nor post-operative complications were reported during
      the study. The surgical team noticed a good perception of depth and easy
      recognising of anatomic structures, especially concerning the upper and lower
      vascular pedicle, the parathyroids, the superior and inferior laryngeal nerves.
      Preliminary impression emerging from this study seems to suggest that 3D MIVAT is
      safe and effective. Future studies with larger case series are required to
      determine the role of this procedure. KEYWORDS: MIVAT; 3D; Three dimensional;
      Minimally invasive; Thyroidectomy.

PMID- 24438103
TI  - Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro:
      identification of the active components and JAK2 and gp130 as substrates.
AB  - SOCS3 (suppressor of cytokine signaling 3) inhibits the intracellular signaling
      cascade initiated by exposure of cells to cytokines. SOCS3 regulates signaling
      via two distinct mechanisms: directly inhibiting the catalytic activity of Janus
      kinases (JAKs) that initiate the intracellular signaling cascade and catalysing
      the ubiquitination of signaling components by recruiting components of an E3
      ubiquitin ligase complex. Here we investigate the latter mode-of-action
      biochemically by reconstructing a SOCS3-based E3 ubiquitin ligase complex in
      vitro using fully purified, recombinant components and examining its ability to
      promote the ubiquitination of molecules involved in the cytokine signaling
      cascade. We show that SOCS3 is an active substrate recruitment module for a
      Cullin5-based E3 ligase and have defined the core protein components required for
      ubiquitination. SOCS3-induced polyubiquitination was rapid and could proceed
      through a number of different ubiquitin lysines. SOCS3 catalyzed the
      ubiquitination of both the IL-6 receptor common chain (gp130) and JAK2.

PMID- 24438105
TI  - Stent strut protrusion--an uncommon complication of stent placement in a fistula.
AB  - Stent strut protrusion through the skin is a rare and a potentially dangerous
      complication from the cannulation of stents placed within arterio-venous fistulas
      and grafts. Such cases are usually managed surgically. We present a case wherein
      strut penetration of an arterio-venous fistula was noted at the distal
      (uncovered) end of a Fluency Plus((r)) tracheo bronchial stent graft. After
      analyzing the various reasons why this may have happened, a nonsurgical approach
      was taken to preserve the access and manage strut protrusion. 

PMID- 24438106
TI  - The transcriptome landscape of Prochlorococcus MED4 and the factors for
      stabilizing the core genome.
AB  - BACKGROUND: Gene gain and loss frequently occurs in the cyanobacterium
      Prochlorococcus, a phototroph that numerically dominates tropical and subtropical
      open oceans. However, little is known about the stabilization of its core genome,
      which contains approximately 1250 genes, in the context of genome streamlining.
      Using Prochlorococcus MED4 as a model organism, we investigated the constraints
      on core genome stabilization using transcriptome profiling. RESULTS: RNA-Seq
      technique was used to obtain the transcriptome map of Prochlorococcus MED4,
      including operons, untranslated regions, non-coding RNAs, and novel genes. Genome
      wide expression profiles revealed that three factors contribute to core genome
      stabilization. First, a negative correlation between gene expression levels and
      protein evolutionary rates was observed. Highly expressed genes were
      overrepresented in the core genome but not in the flexible genome. Gene necessity
      was determined as a second powerful constraint on genome evolution through
      functional enrichment analysis. Third, quick mRNA turnover may increase
      corresponding proteins' fidelity among genes that were abundantly expressed.
      Together, these factors influence core genome stabilization during MED4 genome
      evolution. CONCLUSIONS: Gene expression, gene necessity, and mRNA turnover
      contribute to core genome maintenance during cyanobacterium Prochlorococcus genus
      evolution.

PMID- 24438107
TI  - Microbial synthesized biodegradable PHBHHxPEG hybrid copolymer as an efficient
      intracellular delivery nanocarrier for kinase inhibitor.
AB  - BACKGROUND: Protein Kinases are key regulators of cell function and play
      essential roles in the occurrence and development of many human diseases. Many
      kinase inhibitors have been used for molecular targeted treatment of those
      diseases such as cancer and inflammation. However, those highly hydrophobic
      kinase inhibitors shared the common features of poor bioavailability and limited
      in vivo half-life, which strongly impeded their practical applications. Our
      previous study demonstrated that microbial synthesized biodegradable polyester
      poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), a member of
      polyhydroxyalkanoates (PHAs) family, could serve as a promising delivery
      nanocarrier for those hydrophobic kinase inhibitors. Recently, a novel natural
      synthesized hybrid copolymer, PEG200 end-capped PHBHHx (PHBHHxPEG) was produced
      by Aeromonas hydrophila fermentation. In this study, the novel PHBHHxPEG NPs were
      prepared and investigated to serve as intracellular delivery nanocarriers for
      sustained release of hydrophobic kinase inhibitors. RESULTS: PHBHHxPEG
      nanoparticles (NPs) prepared by an emulsification-solvent evaporation method were
      spherical with a diameter around 200 nm. The entrapment efficiency on rapamycin
      in PHBHHxPEG NPs was 91.9% and the sustained release of rapamycin from PHBHHxPEG
      NPs could be achieved for almost 10 days. The cellular uptake of PHBHHxPEG NPs
      was significant higher than that of PHBHHx NPs. The anti-proliferation effect and
      mTOR inhibition ability of rapamycin-loaded PHBHHxPEG NPs was stronger than that
      of drug-loaded PHBHHx NPs and free rapamycin. CONCLUSIONS: PHBHHxPEG NPs could
      achieve the efficient entrapment and sustained release of rapamycin. The novel
      biodegradable PHBHHxPEG appeared a promising nanocarrier for sustained delivery
      of hydrophobic kinase inhibitors with improved cellular uptake and kinase
      inhibition efficiency.

PMID- 24438108
TI  - Chemical burn due to prolonged exposure to the inflatable cuff of a
      sphygmomanometer.

PMID- 24438109
TI  - Is drinking alcohol associated with sexual coercion among Ugandan university
      students?: a cross-sectional study.
AB  - BACKGROUND: Sexual coercion is prevalent in sub-Saharan Africa and is a risk
      factor for unintended pregnancies, sexually transmitted infections and mental
      health problems. Alcohol consumption patterns have been suggested to be an
      important factor behind the experience of sexual coercion among university
      students. OBJECTIVE: To study the association between alcohol consumption and the
      experience of sexual coercion among Ugandan university students. METHOD: In 2010,
      1954 Ugandan students participated in a cross sectional survey, conducted in
      Mbarara University of Science and Technology (72% response rate). A self
      administered questionnaire assessed socio-demographic factors, alcohol
      consumption, mental health, and sexual behavior. Multivariable logistic
      regression analysis was used to examine the various predictors of recent
      experience of sexual coercion. The data were stratified by sex. RESULTS: Of the
      1954 students, 27.6% reported having experienced sexual coercion and 16.4% stated
      that they had such an experience recently. Individuals who reported frequent
      consumption of alcohol, or having consumed alcohol often on the occasion of
      sexual intercourse, were found to have a higher probability of recent experiences
      of sexual coercion (OR adjusted 2.29, 95% CI 1.40-3.72, and OR adjusted 2.78, 95%
      CI 1.56-4.97, respectively). These associations were significant even after
      adjusting for potential confounders. A synergistic effect was found between poor
      mental health and frequent consumption of alcohol in conjunction with having sex
      with regard to its impact on recent experiences of sexual coercion. CONCLUSION:
      We found an association between alcohol consumption and experiences of sexual
      coercion among Ugandan university students. Therefore, universities may want to
      consider alcohol prevention under their policy framework, as it could reduce the
      potential risk of sexual coercion.

PMID- 24438110
TI  - Effect of light on expression of clock genes in Xenopus laevis melanophores.
AB  - Light-dark cycles are considered important cues to entrain biological clocks. A
      feedback loop of clock gene transcription and translation is the molecular basis
      underlying the mechanism of both central and peripheral clocks. Xenopus laevis
      embryonic melanophores respond to light with melanin granule dispersion, response
      possibly mediated by the photopigment melanopsin. To test whether light modulates
      clock gene expression in Xenopus melanophores, we used qPCR to evaluate the
      relative mRNA levels of Per1, Per2, Clock and Bmal1 in cultured melanophores
      exposed to light-dark (LD) cycle or constant darkness (DD). LD cycles elicited
      temporal changes in the expression of Per1, Per2 and Bmal1. A 10-min pulse of
      blue light was able to increases the expression of Per1 and Per2. Red light had
      no effect on the expression of these clock genes. These data suggest the
      participation of a blue-wavelength sensitive pigment in the light-dark cycle
      mediated oscillation of the endogenous clock. Our results add an important
      contribution to the emerging field of peripheral clocks, which in nonmammalian
      vertebrates have been mostly studied in Drosophila and Danio rerio. Within this
      context, we show that X. laevis melanophores, which have already led to
      melanopsin discovery, represent an ideal model to understanding circadian
      rhythms. 

PMID- 24438111
TI  - Commentary on Freelemyer et al. (2014): medication-assisted treatment in Africa
      need is growing but response remains tepid.

PMID- 24438112
TI  - Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk
      driving among previously convicted drunk-driving offenders: results from the
      recidivism of alcohol-impaired driving (ROAD) study.
AB  - AIM: In several European countries, drivers under the influence (DUI), suspected
      of chronic alcohol abuse are referred for medical and psychological examination.
      This study (the ROAD study, or Recidivism Of Alcohol-impaired Driving)
      investigated the usefulness of indirect alcohol biomarkers for predicting drunk
      driving recidivism in previously convicted drunk-driving offenders. DESIGN,
      SETTING, PARTICIPANTS AND MEASUREMENTS: The ROAD study is a prospective study
      (2009-13) that was performed on 517 randomly selected drivers in Belgium. They
      were convicted for drunk-driving for which their licence was confiscated. The
      initial post-arrest blood samples were collected and analysed for percentage
      carbohydrate-deficient transferrin (%CDT), transaminsase activities [alanine
      amino transferase (ALT), aspartate amino transferase (AST)], gamma
      glutamyltransferase (gammaGT) and red cell mean corpuscular volume (MCV). The
      observation time for each driver was 3 years and dynamic. FINDINGS: A logistic
      regression analysis revealed that ln(%CDT) (P < 0.001), ln(gammaGT) (P < 0.01)
      and ln(ALT) (P < 0.05) were the best biochemical predictors of recidivism of
      drunk-driving. The ROAD index (which includes ln(%CDT), ln(gammaGT), -ln(ALT) and
      the sex of the driver) was calculated and had a significantly higher area under
      the receiver operator characteristic curve (0.71) than the individual biomarkers
      for drunk-driving recidivism. Drivers with a high risk of recidivating (ROAD
      index >= 25%; third tertile) could be distinguished from drivers with an
      intermediate risk (16% <= ROAD index < 25%; second tertile; P < 0.001) and a low
      recidivism risk (ROAD index < 16%; first tertile; P < 0.05). CONCLUSIONS: Of all
      routinely used indirect alcohol markers, percentage of carbohydrate-deficient
      transferrin is the major predictor of recidivism of drunk-driving. The
      association with gamma-glutamyltransferase, alanine amino transferase and the sex
      of the driver could have additional value for identifying drunk-drivers at
      intermediate risk of recidivism. Non-specific indirect alcohol markers, such as
      alanine amino transferase, gamma-glutamyltransferase, aspartate amino transferase
      and red cell mean corpuscular volume have minimal added value to % carbohydrate
      deficient transferrin for distinguishing drunk drivers with a low or high risk of
      recidivism.

PMID- 24438113
TI  - Commentary on Hser et al. (2014): to retain or not to retain-open questions in
      opioid maintenance therapy.

PMID- 24438114
TI  - Commentary on Degenhardt et al. (2014): cohort studies enhance the picture of
      drug-related deaths.

PMID- 24438115
TI  - Commentary on Chen et al. (2014): another step on the road to clinical utility of
      pharmacogenetics for smoking cessation?

PMID- 24438116
TI  - A second-class science? A defence of observational epidemiology to make causal
      inferences.

PMID- 24438117
TI  - Second-class evidence for causality, not second-class science.

PMID- 24438119
TI  - Safety and efficacy of bevacizumab combined with R-CHOP regimen in seven Chinese
      patients with untreated diffuse large B-cell lymphoma.
AB  - BACKGROUND: Rituximab plus CHOP (R-CHOP) significantly improved the outcome of
      diffuse large B cell lymphoma (DLBCL), a common sub-type of non-Hodgkin lymphoma.
      But 40% - 50% of DLBCL patients cannot be cured by this regimen. Some clinical
      trials showed that bevacizumab might be useful in the treatment of DLBCL. This
      study evaluated the safety and efficacy of bevacizumab combined with the R-CHOP
      (A-R-CHOP) regimen in Chinese patients with previously untreated DLBCL. METHODS:
      Patients with previously untreated DLBCL received A-R-CHOP regimen therapy. All
      patients with complete response (CR)/ unconfirmed complete response(CRu) after 8
      cycles of A-R-CHOP received the bevacizumab maintenance therapy once every 3
      weeks. The remained bulky disease was treated with radiotherapy. RESULTS: Seven
      Chinese patients were treated. All of them had bulky diseases. One patient had
      progressive disease after 4 cycles of A-R-CHOP therapy. The rest six patients
      completed 8 cycles of A-R-CHOP treatment. All of these six patients reached
      CR/CRu (5 CR, 1 CRu). Bevacizumab maintenance therapy was given to 4 CR patients.
      All 7 patients experienced Grade 3/4 hematologic adverse events; additionally,
      one had Grade 3 gastrointestinal toxicity and one had Grade 1 epistaxis. During
      bevacizumab maintenance therapy, one patient had Grade 1 gingival bleeding,
      another experienced Grade 1 proteinuria and then Grade 3 congestive heart failure
      4 months after completion of maintenance therapy. At the end of July 2013, the
      patient who had progressive disease after 4 cycles of A-R-CHOP died of
      progressive disease, the other six remained CR response. CONCLUSIONS: The A-R
      CHOP regimen is effective for untreated DLBCL, but may cause bevacizumab-specific
      toxicities, which should be monitored.

PMID- 24438121
TI  - Diffusion of two botulinum toxins type A on the forehead: double-blinded,
      randomized, controlled study.
AB  - BACKGROUND: Different diffusion of different botulinum toxin type A (BoNTA)
      preparations may account for differences in outcomes in cosmetic clinical
      practice. OBJECTIVES: A double-blind, randomized, self-controlled study was
      performed to evaluate the diffusion characteristics of onabotulinumtoxinA and a
      Chinese type A botulinum toxin (CBTX-A). MATERIALS AND METHODS: Healthy
      volunteers (N = 20) were recruited to receive a 0.05-mL (2 U) injection of BoTNA
      at four forehead sites (medial forehead (subcutaneous (SC)) and temporal forehead
      (intradermal (ID))). On day 14, the Minor's iodine starch test was performed and
      photographs were taken for calculating the area and dimensions of anhydrotic
      area. RESULTS: When BoNTAs were different, the anhidrosis ID area was
      significantly greater with CBTX-A than onabotulinumtoxinA, the vertical dimension
      was significantly longer with CBTX-A ID than onabotulinumtoxinA ID and the
      horizontal dimension was significantly greater with CBTX-A ID than
      onabotulinumtoxinA ID. The area of anhidrosis SC was significantly greater with
      CBTX-A than onabotulinumtoxinA. When injection depths were different, the mean
      horizontal dimension was significantly greater with onabotulinumtoxinA SC than
      ID. Comparing the dimension of the same BoNTA and injection method, the vertical
      dimension was significantly greater than the horizontal dimension. CONCLUSION:
      OnabotulinumtoxinA diffuses less than CBTX-A. ID injection technique may result
      in less diffusion than SC.

PMID- 24438122
TI  - The Bordetella pertussis Bps polysaccharide enhances lung colonization by
      conferring protection from complement-mediated killing.
AB  - Bordetella pertussis is a human-restricted Gram-negative bacterial pathogen that
      causes whooping cough or pertussis. Pertussis is the leading vaccine preventable
      disease that is resurging in the USA and other parts of the developed world.
      There is an incomplete understanding of the mechanisms by which B. pertussis
      evades killing and clearance by the complement system, a first line of host
      innate immune defence. The present study examined the role of the Bps
      polysaccharide to resist complement activity in vitro and in the mouse
      respiratory tract. The isogenic bps mutant strain containing a large non-polar in
      frame deletion of the bpsA-D locus was more sensitive to serum and complement
      mediated killing than the WT strain. As determined by Western blotting, flow
      cytometry and electron microscopic studies, the heightened sensitivity of the
      mutant strain was due to enhanced deposition of complement proteins and the
      formation of membrane attack complex, the end-product of complement activation.
      Bps was sufficient to confer complement resistance as evidenced by a Bps
      expressing Escherichia coli being protected by serum killing. Additionally,
      Western blotting and flow cytometry assays revealed that Bps inhibited the
      deposition of complement proteins independent of other B. pertussis factors. The
      bps mutant strain colonized the lungs of complement-deficient mice at higher
      levels than that observed in C57Bl/6 mice. These results reveal a previously
      unknown interaction between Bps and the complement system in controlling B.
      pertussis colonization of the respiratory tract. These findings also make Bps a
      potential target for the prevention and therapy of whooping cough. 

PMID- 24438124
TI  - Is intrauterine growth appropriate to monitor postnatal growth of preterm
      neonates?
AB  - When using the useful 2013 Fenton Chart, data should be interpreted with caution
      taking into account two aspects: the physiologic loss of body water after birth
      for the weight curves, and the questionable accuracy of the birth length curves
      considering the heterogeneity and reliability of the methods used in the original
      measurements. 

PMID- 24438123
TI  - Having diabetes and having to fast: a qualitative study of British Muslims with
      diabetes.
AB  - BACKGROUND: There are approximately 2.7 million Muslims in the UK, constituting
      4.8% of the population. It is estimated that 325,000 UK Muslims have diabetes.
      Whilst dietary practices of Muslims with diabetes have been explored, little work
      has described the beliefs and decisions to fast during Ramadan, whereby Muslims
      with diabetes refrain from eating, drinking and taking medication between sunrise
      and sunset. OBJECTIVE: To explore beliefs and experiences of fasting during
      Ramadan of Muslim respondents with diabetes and their perceptions of the role
      played by their general practitioner (GP) and/or practice nurse (PN) in
      supporting them. DESIGN: Qualitative study. SETTING: General practices and
      community groups located in Greater Manchester. PARTICIPANTS: 23 South Asian
      Muslims. METHODS: Semi-structured interviews were conducted as part of the
      Collaboration of Applied Health Research and Care (CLAHRC) programme, Greater
      Manchester. Respondents were recruited using random and purposive sampling
      techniques. Interviews were analysed thematically using a constant comparison
      approach. RESULTS: Thirteen respondents reported they fasted and altered diabetes
      medication and diet during Ramadan. The decision to fast was influenced by
      pressures from the family and the collective social aspect of fasting, and
      respondents made limited contact with primary care during fasting. CONCLUSION:
      Tensions exist between the respondent's personal desire to fast or not fast and
      their family's opinion on the matter, with a strong reluctance to disclose
      fasting to GP and/or PN. Future research needs to explore whether GPs or PNs feel
      competent enough to support patients who wish to fast.

PMID- 24438126
TI  - Detection of chromosomal bla(CTX-M-2) in diverse Escherichia coli isolates from
      healthy broiler chickens.
AB  - The rise of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in
      food-producing animals is a growing concern for public health. We investigated
      ESBL producers isolated from broiler chickens in Brazil and characterized 19 CTX
      M-2-producing E. coli. The ISCR1 was detected upstream of the chromosome-located
      gene bla(CTX-M-2), associated with sul-1 type integron structure. CTX-M-2
      producing E. coli exhibited different PFGE-types and phylogenetic groups, showing
      a non-clonal dissemination. The sequence types found (ST93, ST155 and ST2309)
      have been associated with humans and animals worldwide. Herein, we report the
      chromosomal location of bla(CTX-M-2) on E. coli, highlighting the risks of
      multidrug-resistant bacteria in food-producing animals.

PMID- 24438127
TI  - The midterm outcome and MACE of robotically enhanced grafting of left anterior
      descending artery with left internal mammary artery.
AB  - BACKGROUND: We assessed the midterm outcome and the incidence of major adverse
      cardiovascular events in UK's largest Da Vinci assisted robotic coronary
      revascularisation cohort. This study was set up at the Imperial College NHS
      Trust, St. Mary's Hospital, London, United Kingdom. METHOD: Benchmarking approach
      through retrospective audit of the regional outcomes against standards in the
      published literature. Data was collected from the patient's records,
      communication with the primary care physicians and the national strategic tracing
      service. The results were compared with the published literature. Patients who
      underwent robotic assisted coronary revascularisation were included. Other
      robotic procedures or minimally invasive revascularisation without the use of the
      Da Vinci robot were excluded. The main outcome measure was the midterm survival
      up to five years and the incidence of major adverse cardiovascular events (MACE)
      up to three years. RESULTS: Since April 2002, one hundred consecutive patients
      underwent either off pump robotic assisted single vessel small thoracotomy (SVST,
      n=88), or off pump total endoscopic coronary artery bypass grafting (TCAB, n=12).
      All patients were operated on by the same primary surgeon but different assisting
      surgeons. All patients received a left internal mammary arterial (LIMA) graft as
      planned. The primary outcome of total one month and three years MACE and up to
      five year survival was 0, 9 and 96% respectively. CONCLUSIONS: The procedural
      success rates in terms of morbidity and mortality up to five years are compatible
      to the outcomes observed outside the United Kingdom. These results are not
      inferior to that of conventional off pump single vessel coronary surgery or
      percutaneous coronary intervention to the LAD.

PMID- 24438128
TI  - A randomised sham-controlled trial to assess the long-term effect of the Epley
      manoeuvre for treatment of posterior canal benign paroxysmal positional vertigo.
AB  - OBJECTIVE: To evaluate the long-term efficacy of the Epley manoeuvre as a
      therapeutic procedure for posterior canal benign paroxysmal positional vertigo.
      DESIGN: Randomised, double-blind, sham-controlled trial. SETTING: A
      multidisciplinary dizziness unit in a non-academic Hospital. PARTICIPANTS: Forty
      four patients with posterior canal benign paroxysmal positional vertigo (BPPV)
      with a duration of at least 1 month. Participants were randomised in two groups
      of 22 and treated with either the Epley manoeuvre or a sham manoeuvre and
      followed up for 1 year after treatment. MAIN OUTCOME MEASURES: Conversion of a
      'positive' Dix-Hallpike test to a 'negative' Dix-Hallpike test, impairments
      perceived by the dizziness assessed by the Dizziness Handicap Inventory (DHI).
      STATISTICAL ANALYSIS: Absolute and relative risks were computed, and Fisher's
      exact test was used to compare the treatments. RESULTS: Six patients were lost to
      follow up (five in the sham group, one in the Epley group). The Epley procedure
      resulted in a treatment success in 20/22 patients (91%) after 12 months of follow
      up, whereas the sham procedure had a positive effect in 10/22 patients (46%; P =
      0.001). The DHI was significantly lower in the Epley group at all follow-up
      assessments (median scores 12 months 0 (0-51) versus 20 (0-76), P = 0.003).
      CONCLUSION: The Epley manoeuvre provides long-term resolution of symptoms in
      patients with posterior canal BPPV.

PMID- 24438129
TI  - C-terminal peptides modelling constitutive PrPC processing demonstrate
      ameliorated toxicity predisposition consequent to alpha-cleavage.
AB  - Misfolding of PrPC (cellular prion protein) to beta-strand-rich conformations
      constitutes a key event in prion disease pathogenesis. PrPC can undergo either of
      two constitutive endoproteolytic events known as alpha- and beta-cleavage,
      yielding C-terminal fragments known as C1 and C2 respectively. It is unclear
      whether C-terminal fragments generated through alpha- and beta-cleavage,
      especially C2, influence pathogenesis directly. Consequently, we compared the
      biophysical properties and neurotoxicity of recombinant human PrP fragments
      recapitulating alpha- and beta-cleavage, namely huPrP-(112-231) (equating to C1)
      and huPrP-(90-231) (equating to C2). Under conditions we employed, huPrP-(112
      231) could not be induced to fold into a beta-stranded isoform and neurotoxicity
      was not a feature for monomeric or multimeric assemblies. In contrast, huPrP-(90
      231) easily adopted a beta-strand conformation, demonstrated considerable
      thermostability and was toxic to neurons. Synthetic PrP peptides modelled on
      alpha- and beta-cleavage of the unique Y145STOP (Tyr145->stop) mutant prion
      protein corroborated the differential toxicity observed for recombinant huPrP
      (112-231) and huPrP-(90-231) and suggested that the persistence of soluble
      oligomeric beta-strand-rich conformers was required for significant
      neurotoxicity. Our results additionally indicate that alpha- and beta-cleavage of
      PrPC generate biophysically and biologically non-equivalent C-terminal fragments
      and that C1 generated through alpha-cleavage appears to be pathogenesis-averse. 

PMID- 24438132
TI  - Targeted cancer therapies part 1 #276.

PMID- 24438133
TI  - Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling
      changes.
AB  - Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening
      allergic eye disease, occurring mainly in children. Conventional therapy for
      allergic conjunctivitis is generally not adequate for VKC. Pediatricians and
      allergists are often not familiar with the severe clinical symptoms and signs of
      VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists
      should be aware of the management and therapeutic options for this disease to
      allow patients to enter clinical remission with the least side effects and
      sequelae. Children with VKC present with severe ocular symptoms, that is, severe
      eye itching and irritation, constant tearing, red eye, eye discharge, and
      photophobia. On examination, giant papillae are frequently observed on the upper
      tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous
      infiltrations around the limbus surrounding the cornea (Horner-Trantas dot).
      Conjunctival injections are mostly severe with thick mucus ropy discharge.
      Eosinophils are the predominant cells found in the tears and eye discharge.
      Common therapies include topical antihistamines and dual-acting agents, such as
      lodoxamide and olopatadine. These are infrequently sufficient and topical
      corticosteroids are often required for the treatment of flare ups. Ocular surface
      remodeling leads to severe suffering and complications, such as corneal
      ulcers/scars. Other complications include side effects from chronic topical
      steroids use, such as increased intraocular pressure, glaucoma, cataract and
      infections. Alternative therapies for VKC include immunomodulators, such as
      cyclosporine A and tacrolimus. Surgery is reserved for those with complications
      and should be handled by ophthalmologists with special expertise. Newer research
      on the pathogenesis of VKC is reviewed in this article. Vernal
      keratoconjunctivitis is a very important allergic eye disease in children.
      Complications and remodeling changes are unique and can lead to blindness.
      Understanding of pathogenesis of VKC may lead to better therapy for these
      unfortunate patients.

PMID- 24438134
TI  - Disentangling direct and indirect effects of experimental grassland management
      and plant functional-group manipulation on plant and leafhopper diversity.
AB  - BACKGROUND: Plant biodiversity can affect trophic interactions in many ways,
      including direct bottom-up effects on insects, but is negatively affected by
      agricultural intensification. Grassland intensification promotes plant
      productivity, resulting in changes in plant community composition, and impacts on
      higher trophic levels. Here, we use a novel grassland management experiment
      combining manipulations of cutting and fertilization with experimental changes in
      plant functional group composition (independent of management effects) to
      disentangle the direct and indirect effects of agricultural management on insect
      herbivore diversity and abundance. We used leafhoppers as model organisms as they
      are a key insect taxon in grasslands and react rapidly to management changes.
      Leafhoppers were sampled between May and September 2010 using standardized sweep
      netting and pan traps. RESULTS: Plant diversity, functional group composition and
      management regime in grasslands affected leafhopper species richness and
      abundance. Higher cutting frequencies directly led to decreasing leafhopper
      species richness, presumably due to the higher disturbance frequency and the
      reduction in food-resource heterogeneity. In contrast, fertilizer application had
      only a small indirect negative effect via enhanced aboveground plant biomass,
      reduced plant diversity and changes in functional group composition. The
      manipulated increase in grass cover had contrasting direct and indirect effects
      on leafhopper species richness: grass cover directly increased leafhopper species
      richness, but negatively affected plant diversity, which in turn was positively
      related to leafhopper species richness. In conclusion, insect diversity is driven
      in complex direct and indirect ways by grassland management, including changes in
      functional group composition. CONCLUSIONS: The availability of preferred food
      sources and the frequency of disturbance are important direct and indirect
      drivers of leafhopper species richness, interacting in complex ways with plant
      diversity and food resource heterogeneity.

PMID- 24438136
TI  - New Year's greetings.

PMID- 24438137
TI  - Preface to Journal of Dermatology special issue: lymphomas in Asia.

PMID- 24438138
TI  - Cutaneous lymphoma in Japan: a nationwide study of 1733 patients.
AB  - Types of cutaneous lymphoma (CL) and their incidences may vary among geographic
      areas or ethnic groups. The present study aimed to investigate the incidences of
      various CL in Japan, using epidemiological data from a nationwide registration
      system for CL. Between 2007 and 2011, 1733 new patients with CL were registered
      from over 600 dermatological institutes in Japan. The 1733 patients registered
      included 1485 (85.7%) patients with mature T- and natural killer (NK)-cell
      neoplasms, 224 (12.9%) with B-cell neoplasms and 24 (1.4%) with blastic
      plasmacytoid dendritic cell neoplasm. Mycosis fungoides (MF) is the most common
      CL subtype in the present study (750 patients, 43.3%). The proportion of MF
      patients with early-stage disease was 73%, similar to that of previous studies
      from other cohorts. The incidence rates of adult T-cell leukemia/lymphoma and
      extranodal NK/T-cell lymphoma, nasal type were 16.7% and 2.0%, respectively,
      which may account for the higher incidence of mature T- and NK-cell neoplasms in
      Japan, as compared with that in the USA and Europe. A male predominance was
      observed in most types of CL, except for several CL subtypes such as subcutaneous
      panniculitis-like T-cell lymphoma. 

PMID- 24438135
TI  - Breast cancer follow-up strategies in randomized phase III adjuvant clinical
      trials: a systematic review.
AB  - The effectiveness of different breast cancer follow-up procedures to decrease
      breast cancer mortality are still an object of debate, even if intensive follow
      up by imaging modalities is not recommended by international guidelines since
      1997. We conducted a systematic review of surveillance procedures utilized, in
      the last ten years, in phase III randomized trials (RCTs) of adjuvant treatments
      in early stage breast cancer with disease free survival as primary endpoint of
      the study, in order to verify if a similar variance exists in the scientific
      world. Follow-up modalities were reported in 66 RCTs, and among them, minimal and
      intensive approaches were equally represented, each being followed by 33 (50%)
      trials. The minimal surveillance regimen is preferred by international and North
      American RCTs (P = 0.001) and by trials involving more than one country (P =
      0.004), with no relationship with the number of participating centers (P =
      0.173), with pharmaceutical industry sponsorship (P = 0.80) and with trials
      enrolling > 1000 patients (P = 0.14). At multivariate regression analysis, only
      geographic location of the trial was predictive for a distinct follow-up
      methodology (P = 0.008): Western European (P = 0.004) and East Asian studies (P =
      0.010) use intensive follow-up procedures with a significantly higher frequency
      than international RCTs, while no differences have been detected between North
      American and international RCTs. Stratifying the studies according to the date of
      beginning of patients enrollment, before or after 1998, in more recent RCTs the
      minimal approach is more frequently followed by international and North American
      RCTs (P = 0.01), by trials involving more than one country (P = 0.01) and with
      more than 50 participating centers (P = 0.02). It would be highly desirable that
      in the near future breast cancer follow-up procedures will be homogeneous in RCTs
      and everyday clinical settings. KEYWORDS: Breast cancer; Follow-up; Phase III
      clinical trial; Systematic review.

PMID- 24438139
TI  - Immunological milieu in mycosis fungoides and Sezary syndrome.
AB  - Tumor genesis and development are driven by a combination of intrinsic events
      such as oncogene activation and tumor-suppressor gene inactivation, and extrinsic
      events that are dependent on the interaction with the stroma. Different types of
      growth factors, cytokines and chemokines secreted by the surrounding stromal
      cells are thought to play key roles in solid tumor progression. Accumulating
      evidence indicates that the immunological milieu plays an essential role in tumor
      development, not only in solid tumors, but also in hematopoietic malignancies.
      Understanding the interactions between tumor cells and microenvironment in
      mycosis fungoides (MF) and Sezary syndrome (SS) could provide a basis for the
      development of new treatments for these diseases that are sometimes resistant to
      current therapies. This article focuses on the wide variety of cell types and
      immunological milieus, affecting the characteristic features of MF and SS, such
      as skin-homing of tumor cells, T-helper type 2-dominant tumor microenvironment,
      accumulation of dermal dendritic cells, epidermal hyperplasia, angiogenesis and
      pruritus. 

PMID- 24438140
TI  - Skin manifestations of adult T-cell leukemia/lymphoma: clinical, cytological and
      immunological features.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T cells caused by
      human T-cell leukemia virus type I. The endemic areas include Japan, especially
      in Kyushu, the Caribbean, Papua New Guinea, South America and Africa.
      Approximately 50% of ATLL patients exhibit skin manifestations. Cytologically,
      ATLL tumor cells are characterized by CD4(+) CD25(+) regulatory T-cell phenotype,
      high expressions of CCR4, and programmed cell death (PD)-1 and PD-ligand 1. The
      skin eruptions are categorized into six types: patch, plaque, multipapular,
      nodulotumoral, erythrodermic and purpuric. The overall survival of the eruption
      bearing patients was poorer than that of the non-eruption-bearing patients in
      acute, chronic and smoldering types, but the survival levels of both groups were
      comparable in lymphoma type. The prognosis was poor in the order of:
      erythrodermic, nodulotumoral, multipapular/purpuric, plaque, then patch.
      Multivariate analysis revealed that the eruption type is an independent
      prognostic factor for ATLL. Patients may have other skin manifestations,
      secondary and infective lesions. 

PMID- 24438141
TI  - Meeting report on the possible proposal of an extranodal primary cutaneous
      variant in the lymphoma type of adult T-cell leukemia-lymphoma.
AB  - Based on the advances in research on the clinicopathophysiology of adult T-cell
      leukemia-lymphoma (ATL), Japanese researchers collected and evaluated cases of
      smoldering ATL exhibiting primary cutaneous manifestation but showing poor
      prognosis. Macroscopic findings of skin eruptions were categorized into the
      patch, plaque, multipapular, nodulotumoral, erythrodermic and purpuric types, as
      previously reported. Pathological findings were divided into low or high grade
      based on epidermotropism, tumor cell size and perivascular infiltration. Eight
      eligible cases were evaluated among 14 collected cases. Macroscopic findings were
      nodulotumoral in six cases, a subcutaneous tumor in one case and plaque in one
      case, and the number and size were heterogeneous in each case. Pathological
      findings of all eight cases were T-cell lymphoma, high-grade type (pleomorphic,
      medium or large size), with prominent perivascular infiltration and scant
      epidermotropism. To diagnose such cases as the "lymphoma type of ATL, extranodal
      primary cutaneous variant", it is essential to examine each case carefully,
      including cutaneous lesions at onset, lymph nodes and other organ involvement
      using computed tomography (CT) and/or positron emission tomography/CT, as well as
      the percentage of abnormal lymphocytes in peripheral blood. Based on the results
      of an ongoing nationwide survey on ATL, ATL with cutaneous lesions will be
      analyzed to investigate the incidence and prognosis of the so-called "lymphoma
      type of ATL, extranodal primary cutaneous variant". 

PMID- 24438142
TI  - Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative
      disorders.
AB  - Primary infection with Epstein-Barr virus (EBV) is usually asymptomatic and, in a
      normal host, EBV remains latent in B cells after primary infection for the
      remainder of life. Uncommonly, EBV can infect T or natural killer (NK) cells in a
      person with a defect in innate immunity, and EBV infection can cause unique
      systemic lymphoproliferative diseases (LPD) of childhood. Primary infection in
      young children can be complicated by hemophagocytic lymphohistiocytosis or
      fulminant systemic T-cell LPD of childhood. Uncommonly, patients can develop
      chronic active EBV (CAEBV) disease-type T/NK LPD, which includes CAEBV infection
      of the systemic form, hydroa vacciniforme-like T-cell LPD, and mosquito-bite
      hypersensitivity. The clinical course of CAEBV disease-type T/NK LPD can be
      smoldering, persistent or progressive, depending on the balance between viral
      factors and host immunity. Aggressive NK-cell leukemia, hydroa vacciniforme-like
      T-cell lymphoma, or uncommonly extranodal NK/T-cell lymphoma can develop in
      children and young adults with CAEBV disease-type T/NK-cell LPD. Extranodal T/NK
      cell lymphoma is a disease of adults, and its incidence begins to increase in the
      third decade and comprises the major subtype of T/NK LPD throughout life.
      Aggressive NK-cell leukemia and nodal T/NK-cell lymphoma of the elderly are
      fulminant diseases, and immune senescence may be an important pathogenetic
      factor. This review describes the current progress in identifying different types
      of EBV-associated T/NK-cell LPD and includes a brief presentation of data from
      Korea. 

PMID- 24438143
TI  - Epstein-Barr virus-associated T/natural killer-cell lymphomas in the elderly: the
      first consensus meeting in Kofu 2013.
AB  - From a clinicopathological conference on nine elderly patients with Epstein-Barr
      virus (EBV)-associated T/natural killer (NK)-cell lymphoma, we have addressed the
      patients' backgrounds, clinical manifestations, histopathological findings,
      cytogenesis, complications and prognoses. Among these elderly patients (>65 years
      old), seven patients had extranodal NK/T-cell lymphoma, nasal type (ENKL) with an
      NK-cell phenotype, and two patients had EBV(+) T-cell lymphomas or
      lymphoproliferative disorders (LPD) with cutaneous lesions mimicking pityriasis
      lichenoides et varioliformis acuta (PLEVA) or hydroa vacciniforme (HV). No
      patients had a previous episode of EBV-related symptoms such as infectious
      mononucleosis, chronic active EBV infection, HV or hypersensitivity to mosquito
      bites. Elderly patients with ENKL may show the centroblastoid variant. EBV(+)
      CD8(+) CD56(+/-) lymphocytes may be responsible for the development of PLEVA or
      HV-like cutaneous lesions in the elderly. 

PMID- 24438144
TI  - Current therapy of choice for cutaneous lymphomas: Complementary to the Japanese
      Dermatological Association/Japanese Skin Cancer Society guidelines.
AB  - The first Japanese edition of guidelines for management of cutaneous lymphoma was
      published jointly in 2009 by the Japanese Dermatological Association (JDA) and
      the Japanese Skin Cancer Society (JSCS) - Lymphoma Study Group; the guidelines
      were revised in 2011, and published in English in 2013. The JDA/JSCS guidelines
      are unique because they describe information and management practices for
      lymphomas specific to Asia, such as adult T-cell leukemia/lymphoma and extranodal
      natural killer/T-cell lymphoma, nasal type. In the present article, we have
      highlighted the essential points of management for cutaneous lymphomas in Asia.
      In order to complement the guidelines, we have added further information and our
      clinical experience of some currently available agents for cutaneous lymphomas in
      Japan. 

PMID- 24438145
TI  - Depsipeptide and roxithromycin induce apoptosis of lymphoma cells by blocking
      extracellular signal-regulated kinase activation.
AB  - Depsipeptide (FK228), a histone deacetylase inhibitor, was recently approved for
      use in cutaneous T-cell lymphoma. Roxithromycin (RXM) is a macrolide antibiotic
      that can induce apoptosis of some T-cell lines. In this study, we investigated
      whether combination of FK228 and RXM had a synergistic inhibitory effect on cell
      survival of various lymphoma cells and which signaling pathway was affected by
      the drugs in the presence or absence of chemokines, which were reported to
      inhibit apoptosis of some tumor cells. FK228 and RXM additively decreased the
      number of HUT-78, Ki-JK and EL-4 lymphoma cells at doses over 50 nmol/L and 50
      MUmol/L, respectively. These drugs inhibited phosphorylation of Akt and
      extracellular signal-regulated kinase (ERK) of EL-4 cells in a dose-dependent
      manner. Significant association between ERK phosphorylation and cell number or
      annexin V(+) cells suggested that the ERK pathway may be critical for survival of
      EL-4 cells. Combination of 10 or 50 nmol/L of FK228 and 10 MUmol/L of RXM
      decreased cell number of HUT78 and EL-4 compared to a single use of each drug.
      Our in vitro study suggested that combination of FK228 and RXM may be helpful for
      enhancing tumor killing effects. Although further study is necessary, this
      combination may be applicable to patients with cutaneous T-cell lymphoma in the
      future. 

PMID- 24438146
TI  - Mycosis fungoides palmaris et plantaris successfully treated with radiotherapy:
      case report and mini-review of the published work.
AB  - Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of cutaneous T
      cell lymphoma limited to the palms and soles that is not widely recognized
      because of its uncommon occurrence. We report a 73-year-old Japanese man who
      presented with an erosion on the left dorsal hand, a reddish tumor on the right
      palm, and hyperkeratotic erythematous plaques on the right sole. Skin biopsy
      showed histological features of mycosis fungoides (MF) with invasion into the
      deeper layers of skin. There was no visceral or lymph node invasion. We diagnosed
      this case as MFPP. External beam radiotherapy (EBRT) was performed to treat the
      hand lesions. Combination treatment with topical steroids and topical psoralen
      plus ultraviolet light therapy was performed to treat the right sole lesion, but
      was ineffective. Therefore, sequential EBRT was performed. Complete remission of
      all lesions was obtained. This is the first report of MFPP with a locally
      advanced tumor for which the efficacy of radiotherapy is described in detail.
      MFPP lesions occur on the dorsal aspect of hand or foot, and here we propose a
      classification of MFPP as hand and foot MF. The pathogenesis of MFPP is still
      unclear and further accumulation of data is required. 

PMID- 24438147
TI  - Extranodal natural killer/T-cell lymphoma, nasal type, with prominent
      granulomatous reaction.

PMID- 24438148
TI  - Harlequin color change in two preterm newborns.
AB  - Harlequin color change is a benign transient skin change usually seen in the
      neonatal period with unknown etiology. It has been rarely reported in preterm
      infants. Herein, we report two cases of harlequin color change developed in
      premature infants without any adverse consequences. During the event, one infant
      was receiving antibiotic treatment for an Escherichia coli bacteremia in addition
      to routine supportive care and the other one was in a very stable condition. Both
      preterm infants were also diagnosed to have a patent ductus arteriosus. As a
      benign transient skin change, harlequin color change should be recognized
      properly to avoid unnecessary treatment. 

PMID- 24438149
TI  - Generalized granuloma annulare after bacillus Calmette-Guerin vaccination,
      clinically resembling papular tuberculid.

PMID- 24438150
TI  - Giving cell phones to pregnant women and improving services may increase primary
      health facility utilization: a case-control study of a Nigerian project.
AB  - BACKGROUND: Worldwide, about 287 000 women die each year from mostly preventable
      complications related to pregnancy and childbirth. A disproportionately high
      number of these deaths occur in sub-Saharan Africa. The Abiye ('Safe Motherhood')
      project in the Ifedore Local Government Area (LGA) of Ondo-State of Nigeria aimed
      at improving facility utilization and maternal health through the use of cell
      phones and generally improved health care services for pregnant women, including
      Health Rangers, renovated Health Centres, and improved means of transportation.
      METHODS: A one-year sample of retrospective data was collected from hospital
      records and patients' case files from Ifedore (the project area) and Idanre
      (control area) and was analyzed to determine healthcare facility utilization
      rates in each location. Semi-structured questionnaires were used to generate
      supplemental data. RESULTS: The total facility utilization rate of pregnant women
      was significantly higher in Ifedore than in Idanre. The facility utilization rate
      of the primary health care centres was significantly higher in Ifedore than in
      Idanre. The number of recorded cases of the five major causes of maternal death
      in the two LGAs was not significantly different, possibly because the project was
      new. CONCLUSIONS: Giving cell phones to pregnant women and generally improving
      services could increase their utilization of the primary healthcare system.

PMID- 24438151
TI  - Tracing retinal vessel trees by transductive inference.
AB  - BACKGROUND: Structural study of retinal blood vessels provides an early
      indication of diseases such as diabetic retinopathy, glaucoma, and hypertensive
      retinopathy. These studies require accurate tracing of retinal vessel tree
      structure from fundus images in an automated manner. However, the existing work
      encounters great difficulties when dealing with the crossover issue commonly-seen
      in vessel networks. RESULTS: In this paper, we consider a novel graph-based
      approach to address this tracing with crossover problem: After initial steps of
      segmentation and skeleton extraction, its graph representation can be
      established, where each segment in the skeleton map becomes a node, and a direct
      contact between two adjacent segments is translated to an undirected edge of the
      two corresponding nodes. The segments in the skeleton map touching the optical
      disk area are considered as root nodes. This determines the number of trees to-be
      found in the vessel network, which is always equal to the number of root nodes.
      Based on this undirected graph representation, the tracing problem is further
      connected to the well-studied transductive inference in machine learning, where
      the goal becomes that of properly propagating the tree labels from those known
      root nodes to the rest of the graph, such that the graph is partitioned into
      disjoint sub-graphs, or equivalently, each of the trees is traced and separated
      from the rest of the vessel network. This connection enables us to address the
      tracing problem by exploiting established development in transductive inference.
      Empirical experiments on public available fundus image datasets demonstrate the
      applicability of our approach. CONCLUSIONS: We provide a novel and systematic
      approach to trace retinal vessel trees with the present of crossovers by solving
      a transductive learning problem on induced undirected graphs.

PMID- 24438152
TI  - Home hair removal in all skin types with a combined radiofrequency and optical
      energy source device.
AB  - BACKGROUND: Home hair removal devices are available for skin types I to IV. Side
      effects may limit hair removal in darker-pigmented individuals. OBJECTIVE: To
      evaluate a home hair removal device using combined radiofrequency (RF) and
      intense pulsed light (IPL) energy for effectiveness and safety with all skin
      types (I-VI). DESIGN: Two study designs: effectiveness (treating 94 bilateral
      patient areas weekly seven times, with one side then receiving three additional
      treatments at 4-week intervals) and safety (37 patient areas treated every 2-4
      days for three sessions). MEASUREMENTS: Hairs were counted 3 months after
      treatment for the first design and 2 months after for the second. RESULTS: In the
      first study design, 55% hair count reduction was achieved1 month after seven
      treatments to all sites. The side with no further sessions had 43% hair reduction
      and the side receiving ongoing treatment had 58% reduction after two further
      treatments. Side effects were transient and minor. In the second study, with 46%
      of the patients having skin types V/VI, 2 months after the procedure there was
      44% hair reduction. There were no adverse effects reported. CONCLUSION: For the
      first time, a home hair removal device has been shown to be effective and safe in
      all skin types using a low-energy RF-IPL device.

PMID- 24438153
TI  - Effect of calcium phosphate and vitamin D3 supplementation on bone remodelling
      and metabolism of calcium, phosphorus, magnesium and iron.
AB  - BACKGROUND: The aim of the present study was to determine the effect of calcium
      phosphate and/or vitamin D3 on bone and mineral metabolism. METHODS: Sixty
      omnivorous healthy subjects participated in the double-blind, placebo-controlled
      parallel designed study. Supplements were tricalcium phosphate (CaP) and
      cholecalciferol (vitamin D3). At the beginning of the study (baseline), all
      subjects documented their normal nutritional habits in a dietary record for three
      successive days. After baseline, subjects were allocated to three intervention
      groups: CaP (additional 1 g calcium/d), vitamin D3 (additional 10 MUg/d) and CaP
      + vitamin D3. In the first two weeks, all groups consumed placebo bread, and
      afterwards, for eight weeks, the test bread according to the intervention group.
      In the last week of each study period (baseline, placebo, after four and eight
      weeks of intervention), a faecal (three days) and a urine (24 h) collection and a
      fasting blood sampling took place. Calcium, phosphorus, magnesium and iron were
      determined in faeces, urine and blood. Bone formation and resorption markers were
      analysed in blood and urine. RESULTS: After four and eight weeks, CaP and CaP +
      vitamin D3 supplementations increased faecal excretion of calcium and phosphorus
      significantly compared to placebo. Due to the vitamin D3 supplementations
      (vitamin D3, CaP + vitamin D3), the plasma 25-(OH)D concentration significantly
      increased after eight weeks compared to placebo. The additional application of
      CaP led to a significant increase of the 25-(OH)D concentration already after
      four weeks. Bone resorption and bone formation markers were not influenced by any
      intervention. CONCLUSIONS: Supplementation with daily 10 MUg vitamin D3
      significantly increases plasma 25-(OH)D concentration. The combination with daily
      1 g calcium (as CaP) has a further increasing effect on the 25-(OH)D
      concentration. Both CaP alone and in combination with vitamin D3 have no
      beneficial effect on bone remodelling markers and on the metabolism of calcium,
      phosphorus, magnesium and iron. TRIAL REGISTRATION: NCT01297023.

PMID- 24438154
TI  - Response to letter from Barry & Dennis.

PMID- 24438155
TI  - Impact of cardiopulmonary bypass on acute kidney injury following coronary artery
      bypass grafting: a matched pair analysis.
AB  - BACKGROUND: Postoperative Acute Kidney Injury (AKI) after coronary artery bypass
      grafting (CABG) is a common complication associated with significant morbidity
      and mortality. Cardiopulmonary bypass (CPB) is accepted to contribute to the
      occurrence of AKI and is of particular importance as it can be avoided by using
      the off-pump technique. However the renoprotective properties of off-pump (CABG)
      are controversial. This analysis evaluates the impact of cardiopulmonary bypass
      on renal function. METHODS: A matched-pair analysis of 1428 patients undergoing
      coronary artery bypass grafting was conducted. The patients were stratified
      according to their preoperative renal function and to risk factors for
      postoperative AKI. The development of the glomerular filtration rate (GFR) from
      before surgery until hospital discharge was analyzed. Incidence of AKI were
      analyzed. Furthermore the impact of CPB duration on postoperative GFR was
      assessed. RESULTS: The occurrence of AKI increases the risk of thirty-day
      mortality (odds ratio of 4.3). The postoperative GFR decreases significantly
      after coronary artery bypass grafting but does not differ between onpump and
      offpump CABG (60.2 +/- 24.5 vs 60.7 +/- 24.8; p=0.54). No difference regarding
      the incidence (26.6% vs 25%) and severity of AKI between cardiopulmonary bypass
      and the off-pump technique could be found. Duration of cardiopulmonary bypass
      does not correlate with the decline in postoperative glomerular filtration rate
      (Pearson Product Moment Correlation; p>0.050). CONCLUSION: Neither the mere use
      nor duration of cardiopulmonary bypass proofed to be a risk factor for developing
      postoperative AKI in CABG patients with a comparable preoperative risk profile
      for postoperative renal dysfunction. Furthermore, the severity of postoperative
      AKI is not affected by the use of cardiopulmonary bypass.

PMID- 24438156
TI  - A case of Becker's nevus with pityriasis versicolor.

PMID- 24438158
TI  - Nasal septoplasty with submucosal diathermy to inferior turbinates improves
      symptoms at 3 months postoperatively in a study of one hundred and one patients.

PMID- 24438157
TI  - Functional associations among G protein-coupled neurotransmitter receptors in the
      human brain.
AB  - BACKGROUND: The activity of neurons is controlled by groups of neurotransmitter
      receptors rather than by individual receptors. Experimental studies have
      investigated some receptor interactions, but currently little information is
      available about transcriptional associations among receptors at the whole-brain
      level. RESULTS: A total of 4950 correlations between 100 G protein-coupled
      neurotransmitter receptors were examined across 169 brain regions in the human
      brain using expression data published in the Allen Human Brain Atlas. A large
      number of highly significant correlations were found, many of which have not been
      investigated in hypothesis-driven studies. The highest positive and negative
      correlations of each receptor are reported, which can facilitate the construction
      of receptor sets likely to be affected by altered transcription of one receptor
      (such sets always exist, but their members are difficult to predict). A graph
      analysis isolated two large receptor communities, within each of which receptor
      mRNA levels were strongly cross-correlated. CONCLUSIONS: The presented systematic
      analysis shows that the mRNA levels of many G protein-coupled receptors are
      interdependent. This finding is not unexpected, since the brain is a highly
      integrated complex system. However, the analysis also revealed two novel
      properties of global brain structure. First, receptor correlations are described
      by a simple statistical distribution, which suggests that receptor interactions
      may be guided by qualitatively similar processes. Second, receptors appear to
      form two large functional communities, which might be differentially affected in
      brain disorders.

PMID- 24438159
TI  - Lyme borreliosis caused by diverse genospecies of Borrelia burgdorferi sensu lato
      in northeastern China.
AB  - The variety of Borrelia burgdorferi sensu lato (B. burgdorferi) genospecies leads
      to distinction in clinical manifestations of Lyme borreliosis (LB). There are
      reports of LB clinical characteristics in China, where the B. burgdorferi
      genospecies in ticks and animal hosts are different from those in Europe and
      North America. During May to September in 2010 and 2011, all patients who had
      erythema migrans (EM, more than 5 cm in diameter) after a recent tick-bite, and
      sought medical care at Mudanjiang Forestry Central Hospital, Heilongjiang
      Province of northeastern China, were enrolled in the study. Specific PCR was used
      to determine the B. burgdorferi genospecies in the disseminated patients. Of 265
      EM patients, B. burgdorferi DNA was detected in blood specimens from 15 of 55
      disseminated patients. Sequence analyses of 5S-23S rRNA, flagellin, ospC, 16S
      rRNA and ospA genes revealed that 11 patients were infected with Borrelia
      garinii, three with Borrelia afzelii and one with Borrelia valaisiana-related
      genospecies. Among 15 patients, 40%, 13.3% and 13.3% manifested pruritus, pain
      and ulceration, respectively. Systemic symptoms, arthralgia or a swollen joint
      and lymphadenopathy were observed in 26.7%, 13.3% and 6.7% patients,
      respectively. In northeastern China, three genospecies of LB patients were
      detected. The B. burgdorferi genospecies identified in this study was
      predominantly B. garinii. A case infected with B. valaisiana-related genospecies
      was reported for the first time. 

PMID- 24438160
TI  - Fibroblasts behavior after N-acetylcysteine and amino acids exposure:
      extracellular matrix gene expression.
AB  - Reactive oxygen species (ROS) are chemically reactive molecules with impaired
      electrons that make them unstable and able to react easily with a great variety
      of molecules. The main targets of ROS are DNA, proteins, and membrane
      phospholipids. In the skin, ROS are able to affect the production of collagen and
      elastin, the main components of the extracellular matrix (ECM). This action
      contributes to the skin's aging. N-Acetylcysteine (NAC) is an acetylated cysteine
      residue with excellent anti-oxidant activity that boosts glutathione (GSH)
      levels. This study evaluates the effect of a solution of NAC and amino acids,
      which is used in aesthetic medicine as an intra-dermal injective treatment, on
      fibroblast behavior. To this aim, the expression levels of some ECM-related genes
      (HAS1, HYAL1 ELN, ELANE, MMP2, MMP3, MMP13, COL1A1, COL3A1) were analyzed on
      cultured dermal fibroblasts using real-time reverse transcription polymerase
      chain reaction (RT-PCR). All but two collagen genes were up-regulated after 24 hr
      of treatment.

PMID- 24438161
TI  - Invasion of insect cells by Spiroplasma citri involves spiralin relocalization
      and lectin/glycoconjugate-type interactions.
AB  - Spiroplamas are helical, cell wall-less bacteria belonging to the Class
      Mollicutes, a group of microorganisms phylogenetically related to low G+C, Gram
      positive bacteria. Spiroplasma species are all found associated with arthropods
      and a few, including Spiroplasma citri are pathogenic to plant. Thus S. citri has
      the ability to colonize cells of two very distinct hosts, the plant and the
      insect vector. While spiroplasmal factors involved in transmission by the
      leafhopper Circulifer haematoceps have been identified, their specific
      contribution to invasion of insect cells is poorly understood. In this study we
      provide evidence that the lipoprotein spiralin plays a major role in the very
      early step of cell invasion. Confocal laser scanning immunomicroscopy revealed a
      relocalization of spiralin at the contact zone of adhering spiroplasmas. The
      implication of a role for spiralin in adhesion to insect cells was further
      supported by adhesion assays showing that a spiralin-less mutant was impaired in
      adhesion and that recombinant spiralin triggered adhesion of latex beads. We also
      showed that cytochalasin D induced changes in the surface-exposed
      glycoconjugates, as inferred from the lectin binding patterns, and specifically
      improved adhesion of S. citri wild-type but not of the spiralin-less mutant.
      These results indicate that cytochalasin D exposes insect cell receptors of
      spiralin that are masked in untreated cells. In addition, competitive adhesion
      assays with lectins strongly suggest spiralin to exhibit glycoconjugate binding
      properties similar to that of the Vicia villosa agglutinin (VVA) lectin. 

PMID- 24438162
TI  - Structure of cyclin G-associated kinase (GAK) trapped in different conformations
      using nanobodies.
AB  - GAK (cyclin G-associated kinase) is a key regulator of clathrin-coated vesicle
      trafficking and plays a central role during development. Additionally, due to the
      unusually high plasticity of its catalytic domain, it is a frequent 'off-target'
      of clinical kinase inhibitors associated with respiratory side effects of these
      drugs. In the present paper, we determined the crystal structure of the GAK
      catalytic domain alone and in complex with specific single-chain antibodies
      (nanobodies). GAK is constitutively active and weakly associates in solution. The
      GAK apo structure revealed a dimeric inactive state of the catalytic domain
      mediated by an unusual activation segment interaction. Co-crystallization with
      the nanobody NbGAK_4 trapped GAK in a dimeric arrangement similar to the one
      observed in the apo structure, whereas NbGAK_1 captured the activation segment of
      monomeric GAK in a well-ordered conformation, representing features of the active
      kinase. The presented structural and biochemical data provide insight into the
      domain plasticity of GAK and demonstrate the utility of nanobodies to gain
      insight into conformational changes of dynamic molecules. In addition, we present
      structural data on the binding mode of ATP mimetic inhibitors and enzyme kinetic
      data, which will support rational inhibitor design of inhibitors to reduce the
      off-target effect on GAK. 

PMID- 24438163
TI  - Minimally invasive, imaging guided virtual autopsy compared to conventional
      autopsy in foetal, newborn and infant cases: study protocol for the paediatric
      virtual autopsy trial.
AB  - BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR
      imaging is a promising alternative to conventional autopsy in the investigation
      of infant death. A major drawback of this non-invasive autopsy approach is the
      fact that histopathological and microbiological examination of the tissue is not
      possible. The objective of this prospective study is to compare the performance
      of minimally invasive, virtual autopsy, including CT-guided biopsy, with
      conventional autopsy procedures in a paediatric population. METHODS/DESIGN:
      Foetuses, newborns and infants that are referred for autopsy at three different
      institutions associated with the University of Zurich will be eligible for
      recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI
      scanner, masked to the results of conventional autopsy. After cross-sectional
      imaging, CT-guided tissue sampling will be performed by a multifunctional robotic
      system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy
      results will be classified with regards to the likely final diagnosis and major
      pathological findings and compared to the results of conventional autopsy, which
      remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the
      development of alternative post-mortem examination methods, not only as a
      counselling tool for families and as a quality control measure for clinical
      diagnosis and treatment but also as an instrument to advance medical knowledge
      and clinical practice. This interdisciplinary study will determine whether
      virtual autopsy will narrow the gap in information between non-invasive and
      traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01888380.

PMID- 24438164
TI  - Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll
      catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus.
AB  - The development of complementary and/or alternative drugs for treatment of
      hepatitis C virus (HCV) infection is still needed. Antiviral compounds in
      medicinal plants are potentially good targets to study. Morinda citrifolia is a
      common plant distributed widely in Indo-Pacific region; its fruits and leaves are
      food sources and are also used as a treatment in traditional medicine. In this
      study, using a HCV cell culture system, it was demonstrated that a methanol
      extract, its n-hexane, and ethyl acetate fractions from M. citrifolia leaves
      possess anti-HCV activities with 50%-inhibitory concentrations (IC(50)) of 20.6,
      6.1, and 6.6 MUg/mL, respectively. Bioactivity-guided purification and structural
      analysis led to isolation and identification of pheophorbide a, the major
      catabolite of chlorophyll a, as an anti-HCV compound present in the extracts
      (IC(50) = 0.3 MUg/mL). It was also found that pyropheophorbide a possesses anti
      HCV activity (IC(50) = 0.2 MUg/mL). The 50%-cytotoxic concentrations (CC(50)) of
      pheophorbide a and pyropheophorbide a were 10.0 and 7.2 MUg/mL, respectively,
      their selectivity indexes being 33 and 36, respectively. On the other hand,
      chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only
      marginally, exhibited anti-HCV activities. Time-of-addition analysis revealed
      that pheophorbide a and pyropheophorbide a act at both entry and the post-entry
      steps. The present results suggest that pheophorbide a and its related compounds
      would be good candidates for seed compounds for developing antivirals against
      HCV.

PMID- 24438166
TI  - Common colic, gastroesophageal reflux and constipation in infants under 6 months
      of age do not necessitate an allergy work-up.

PMID- 24438168
TI  - Prognostic factors in patients with terminal stage lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related death.(1) Accurate
      prediction of survival in the terminal stage is important, because it may help
      patients make a rational decision. Although several prognostic scores have been
      described as effective indicators of outcome, these scores were intended for
      patients with other types of cancers. There is no prognostic score for patients
      with terminal-stage lung cancer. OBJECTIVE: The aim of this study was to
      determine prognostic factors for patients with terminal-stage lung cancer.
      SETTING/SUBJECTS: Patients in our palliative care unit (PCU) were selected
      retrospectively and divided into two independent groups, training and testing.
      Univariate and multivariate analyses were performed on data from the training
      group to detect independent prognostic factors, while data from patients in the
      testing group were analyzed to validate whether these prognostic factors
      predicted near-term death. RESULTS: Ninety-three patients (69 in the training
      group and 24 in the testing group) were included in the analyses. Multivariate
      analysis showed that fatigue, anorexia, desaturation, hyponatremia, and
      hypoalbuminemia were independent prognostic factors in the training group. Mean
      survival time in patients who had more than three of these five factors was 9.2+/
      2.6 days (p=0.012). In the testing group, the presence of more than three of
      these five factors predicted death within two weeks, with a sensitivity of 100%
      and specificity of 75%. CONCLUSIONS: This study revealed that fatigue, anorexia,
      desaturation, hyponatremia, and hypoalbuminemia may be short-term prognostic
      factors in terminally ill lung cancer patients. In particular, the presence of
      more than three of these factors predicted death within two weeks.

PMID- 24438167
TI  - miR-302b is a potential molecular marker of esophageal squamous cell carcinoma
      and functions as a tumor suppressor by targeting ErbB4.
AB  - BACKGROUND: ErbB4 expression has been noted in various tumors, but its regulatory
      mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim
      of this study was to investigate whether miR-302b regulates the expression of
      ErbB4 at the post-transcriptional level and to determine its expression,
      significance, and function in ESCC. METHODS: We used real-time reverse
      transcriptase-polymerase chain reaction to quantify the expression of miR-302b in
      50 ESCC tissues and analyzed its relationship with clinicopathological factors
      and survival. Then, we investigated the post-transcriptional regulation of ErbB4
      expression using immunoblot analysis and luciferase reporter assays. Finally, the
      effects of miR-302b on proliferation, apoptosis, and invasion of ESCC cells was
      detected using MTT, flow cytometric analysis, and transwell invasion assays,
      respectively. RESULTS: miR-302b was significantly down-regulated and correlated
      with tumor differentiation and lymph node metastasis in ESCC. Univariate and
      multivariate analyses indicated that low miR-302b expression might be a poor
      prognostic factor. Further studies demonstrated that miR-302b post
      transcriptionally down-regulated the expression of ErbB4 in vitro. Moreover, miR
      302b inhibited proliferation by inducing apoptosis and repressed invasion in the
      ESCC cell lines. CONCLUSIONS: miR-302b is a potential molecular marker of ESCC
      and functions as a tumor suppressor by post-transcriptionally regulating ErbB4.

PMID- 24438169
TI  - Crystal structures of the human Dysferlin inner DysF domain.
AB  - BACKGROUND: Mutations in dysferlin, the first protein linked with the cell
      membrane repair mechanism, causes a group of muscular dystrophies called
      dysferlinopathies. Dysferlin is a type two-anchored membrane protein, with a
      single C terminal trans-membrane helix, and most of the protein lying in
      cytoplasm. Dysferlin contains several C2 domains and two DysF domains which are
      nested one inside the other. Many pathogenic point mutations fall in the DysF
      domain region. RESULTS: We describe the crystal structure of the human dysferlin
      inner DysF domain with a resolution of 1.9 Angstroms. Most of the pathogenic
      mutations are part of aromatic/arginine stacks that hold the domain in a folded
      conformation. The high resolution of the structure show that these interactions
      are a mixture of parallel ring/guanadinium stacking, perpendicular H bond
      stacking and aliphatic chain packing. CONCLUSIONS: The high resolution structure
      of the Dysferlin DysF domain gives a template on which to interpret in detail the
      pathogenic mutations that lead to disease.

PMID- 24438170
TI  - Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta
      analysis of clinical trials.
AB  - BACKGROUND AND AIM: Fenugreek is a herb that is widely used in cooking and as a
      traditional medicine for diabetes in Asia. It has been shown to acutely lower
      postprandial glucose levels, but the long-term effect on glycemia remains
      uncertain. We systematically reviewed clinical trials of the effect of fenugreek
      intake on markers of glucose homeostasis. METHODS: PubMed, SCOPUS, the Cochrane
      Trials Registry, Web of Science, and BIOSIS were searched up to 29 Nov 2013 for
      trials of at least 1 week duration comparing intake of fenugreek seeds with a
      control intervention. Data on change in fasting blood glucose, 2 hour postload
      glucose, and HbA1c were pooled using random-effects models. RESULTS: A total of
      10 trials were identified. Fenugreek significantly changed fasting blood glucose
      by -0.96 mmol/l (95% CI: -1.52, -0.40; I2 = 80%; 10 trials), 2 hour postload
      glucose by -2.19 mmol/l (95% CI: -3.19, -1.19; I2 = 71%; 7 trials) and HbA1c by 
      0.85% (95% CI: -1.49%, -0.22%; I2 = 0%; 3 trials) as compared with control
      interventions. The considerable heterogeneity in study results was partly
      explained by diabetes status and dose: significant effects on fasting and 2 hr
      glucose were only found for studies that administered medium or high doses of
      fenugreek in persons with diabetes. Most of the trials were of low methodological
      quality. CONCLUSIONS: Results from clinical trials support beneficial effects of
      fenugreek seeds on glycemic control in persons with diabetes. However, trials
      with higher methodology quality using a well characterized fenugreek preparation
      of sufficient dose are needed to provide more conclusive evidence.

PMID- 24438171
TI  - Differential expression of microRNAs as predictors of glioblastoma phenotypes.
AB  - BACKGROUND: Glioblastoma is the most aggressive primary central nervous tumor and
      carries a very poor prognosis. Invasion precludes effective treatment and
      virtually assures tumor recurrence. In the current study, we applied analytical
      and bioinformatics approaches to identify a set of microRNAs (miRs) from several
      different human glioblastoma cell lines that exhibit significant differential
      expression between migratory (edge) and migration-restricted (core) cell
      populations. The hypothesis of the study is that differential expression of miRs
      provides an epigenetic mechanism to drive cell migration and invasion. RESULTS:
      Our research data comprise gene expression values for a set of 805 human miRs
      collected from matched pairs of migratory and migration-restricted cell
      populations from seven different glioblastoma cell lines. We identified 62 down
      regulated and 2 up-regulated miRs that exhibit significant differential
      expression in the migratory (edge) cell population compared to matched migration
      restricted (core) cells. We then conducted target prediction and pathway
      enrichment analysis with these miRs to investigate potential associated gene and
      pathway targets. Several miRs in the list appear to directly target apoptosis
      related genes. The analysis identifies a set of genes that are predicted by 3
      different algorithms, further emphasizing the potential validity of these miRs to
      promote glioblastoma. CONCLUSIONS: The results of this study identify a set of
      miRs with potential for decreased expression in invasive glioblastoma cells. The
      verification of these miRs and their associated targeted proteins provides new
      insights for further investigation into therapeutic interventions. The
      methodological approaches employed here could be applied to the study of other
      diseases to provide biomedical researchers and clinicians with increased
      opportunities for therapeutic interventions.

PMID- 24438172
TI  - Comparison of the perceived relevance of oral biology reported by students and
      interns of a Pakistani dental college.
AB  - OBJECTIVES: The purpose of this study was to analyse and compare the perceived
      relevance of oral biology with dentistry as reported by dental students and
      interns and to investigate the most popular teaching approach and learning
      resource. METHODS: A questionnaire aiming to ask about the relevance of oral
      biology to dentistry, most popular teaching method and learning resource was
      utilised in this study. Study groups encompassed second-year dental students who
      had completed their course and dental interns. The data were obtained and
      analysed statistically. RESULTS: The overall response rate for both groups was
      60%. Both groups reported high relevance of oral biology to dentistry. Perception
      of dental interns regarding the relevance of oral biology to dentistry was higher
      than that of students. Both groups identified student presentations as the most
      important teaching method. Amongst the most important learning resources,
      textbooks were considered most imperative by interns, whereas lecture handouts
      received the highest importance score by students. CONCLUSIONS: Dental students
      and interns considered oral biology to be relevant to dentistry, although greater
      relevance was reported by interns. Year-wise advancement in dental education and
      training improves the perception of the students about the relevance of oral
      biology to dentistry.

PMID- 24438173
TI  - Repetitive box lifting performance is impaired in a hot environment: implications
      for altered work-rest cycles.
AB  - This study investigated the effects of environmental temperature on repetitive
      box lifting (RBL) performance, associated stress hormone and creatine kinase (CK)
      responses. Ten healthy males performed two experimental trials in a random
      crossover design. The trials consisted of three 40 min (10 min sitting, 20 min
      standing, and 10 min RBL) circuits performed in either 23  degrees C or 38 
      degrees C followed by a 180 min seated recovery period in 23  degrees C. RBL
      performance (i.e., number of boxes lifted) was reduced (p <= 0.05) in 38  degrees
      C compared to the 23  degrees C trial. Physiological Strain Index was
      significantly different between trials (38  degrees C: 8.5 +/- 1.1 versus 23 
      degrees C: 7.2 +/- 0.7; p <= 0.01). Plasma testosterone was elevated (p <= 0.05)
      across both trials and then decreased at 60 min recovery, compared to pre
      exercise (PRE) measures, but was higher (p <= 0.05) during the 38  degrees C
      trial. Plasma cortisol increased (p <= 0.05) at 60 min during both trials and
      remained elevated until 120 min in 23  degrees C, and until 60 min recovery in 38
      degrees C. Serum CK was greater through 48 hr post compared to PRE values in
      both trials. Thus, 10 min RBL performance was reduced in 38  degrees C despite
      the 30-min rest periods between RBL intervals. Plasma testosterone and cortisol
      were generally higher during the 38  degrees C trial, suggesting a greater stress
      response. Additional research is needed to determine optimal work:rest cycles for
      maximizing work performance in thermally oppressive environments.

PMID- 24438174
TI  - Mitochondria as promising targets for nutritional interventions aiming to improve
      performance and longevity of sows.
AB  - Genetic selection and management changes during the last decades have
      significantly increased the average litter size of sows. However, this recent
      success has not correlated with an extension of longevity and reduction in
      replacement rate. Longevity or lifetime production of sows is determined by a
      combination of environmental and genetic factors. Nutrition is an environmental
      factor of importance, and it has long been appreciated that animals fed with
      specific diets may perform differently. The advent of modern science revealed
      that this is partly due to the ability of nutrients to act as signalling
      molecules that, through appropriate intracellular sensing mechanisms, can control
      gene expression and modulate cell functions. Based on this concept, nutrigenomics
      studies now aim to show that not only are certain nutrients essential for general
      health, but also that specific quantities of precise nutrients are necessary
      during critical periods of energy deficiency and oxidative stress such as
      gestation and lactation to ensure long-term productivity. The toxic molecules at
      the origin of oxidative stress, free radicals, are mainly generated as normal by
      products of aerobic energy production by mitochondria. In all cells, mitochondria
      are dynamic organelles that are mainly known as the primary energy-generating
      system. Thus, when metabolic demands are elevated as it is for hyperprolific
      sows, mitochondria are heavily solicited for answering all energetic needs, and
      substantive amounts of free radicals are generated. As a result, optimal
      conditions in term of antioxidant protection and metabolic substrates
      availability are required to support mitochondrial function in these animals.
      This article discusses how performance and longevity of sows are linked to
      mitochondrial function and oxidative stress and reviews the major natural
      nutrients known for their antioxidant and/or energetic properties that are
      susceptible to impact mitochondria and likely improved sows productivity. 

PMID- 24438175
TI  - Microbe discovery: lessons from the past.

PMID- 24438176
TI  - Systematic review of the limited evidence base for treatments of Eustachian tube
      dysfunction: a health technology assessment.
AB  - BACKGROUND: The Health Technology Assessment programme commissioned a wide
      ranging review of treatments for adult Eustachian tube dysfunction. Treatments
      range from advice and observation and pharmacological treatments to surgical
      options. OBJECTIVE: (i) To assess the evidence for interventions for adults with
      a clinical diagnosis of Eustachian tube dysfunction and (ii) to identify
      priorities for future research. TYPE OF REVIEW: Systematic review (PROSPERO
      registration CRD42012003035) adhering to PRISMA guidance. SEARCH: An extensive
      search of 15 databases including MEDLINE, EMBASE and CENTRAL (up to October
      2012). EVALUATION METHOD: Controlled and uncontrolled studies of interventions
      for adult Eustachian tube dysfunction were included. Because of insufficient
      data, the protocol was amended to also include controlled studies with mixed
      adult/child populations. Risk of bias was assessed. Narrative synthesis was
      employed due to high clinical heterogeneity. RESULTS: Interventions assessed were
      pharmacological treatments [two randomised controlled trials (RCTs), one
      controlled non-randomised trial (CCT), 159 patients]; mechanical pressure
      equalisation devices (one randomised controlled trial, one CCT, 48 patients); and
      surgery, including laser tuboplasty (seven case series, 192 patients), balloon
      dilatation (three case series, 103 patients), myringotomy without grommet
      insertion (two case series, 121 patients), transtubal steroids (one case series,
      11 patients) and laser coagulation (one retrospective controlled study, 40
      patients). All studies had high risk of bias except two pharmacological trials;
      one had low risk and one unclear risk. No evidence was found for many treatments.
      The single low risk of bias RCT (n = 91; 67% adults) showed no effect of nasal
      steroids and favoured placebo for improved middle ear function (RR 1.20, 95% CI
      0.91-1.58) and symptoms (P = 0.07). Other studies showed improvements in middle
      ear function for mechanical devices, antihistamine/ephedrine and nasal
      decongestant, but they had significant methodological weaknesses including
      insufficient length of follow-up. None of the surgical studies were adequately
      controlled, and many reported high levels of co-intervention. Therefore, observed
      benefits for tuboplasty and balloon dilatation in symptoms, middle ear function
      or hearing could not be reliably attributed to the interventions assessed. There
      was variability in definitions of the condition. CONCLUSION: Eustachian tube
      dysfunction is a poorly defined condition. Due to the limited and poor-quality
      evidence, it is inappropriate to make conclusions on the effectiveness of any
      intervention; the evidence base is insufficient to guide recommendations for a
      trial of any particular intervention. Consensus on diagnostic criteria for
      Eustachian tube dysfunction is required to inform inclusion criteria of future
      trials.

PMID- 24438177
TI  - Anti-infective and cytotoxic properties of Bupleurum marginatum.
AB  - BACKGROUND: Bupleurum marginatum Wall. ex DC (Apiaceae) is a perennial herb
      widely used in traditional Chinese and Kampo medicine for the treatment of
      various infectious diseases. The biological activities of B. marginatum have not
      been fully investigated. This study aims to investigate the antitrypanosomal,
      antimicrobial and antiviral activities of methanol (ME) and dichloromethane (DCM)
      extracts of B. marginatum aerial parts and the ability of both extracts to
      inhibit the growth of different cancer cell lines. METHODS: Phytochemical
      characterization of the extracts was performed by LC-MS profiling. The
      antitrypanosomal activity was evaluated using the resazurin method. The
      antimicrobial activity was assessed using agar diffusion and microdilution
      methods, and the minimum inhibitory concentration (MIC) values were determined.
      The antiviral activity was determined for 6.25, 12.5, and 50 MUg/mL doses using a
      plaque reduction assay. Cytotoxicity was investigated in eight cancer cell lines
      (Caco-2, CCL-81, CCRF-CEM, COS-7, HL-60, MIA PaCa-2, MCF-7, and PANC-1) using the
      MTT assay and the caspase 3/7 activity was determined over the range of 62.5-1000
      MUg/mL. RESULTS: Phytochemical analyses resulted in the characterization of 15
      components, mainly flavonoids and lignans. The DCM extract showed significant
      antitrypanosomal activity (IC50: 36.21 MUg/mL) and moderate activity against
      Streptococcus pyogenes (MIC value: 0.25 mg/mL). At a dose of 12.5 MUg/mL, the DCM
      extract inhibited 73.6% of the plaque production by hepatitis A virus. CCRF-CEM
      cells were the most sensitive to both extracts (IC50: 12.5-22.7 MUg/mL). The
      cytotoxicity was mediated by induction of apoptosis (19-fold increase in the
      cellular caspase 3/7 level after treatment with the DCM extract at 1 mg/mL).
      CONCLUSIONS: ME and DCM extract of B. marginatum showed anti-infective and
      antiproliferative effects.

PMID- 24438178
TI  - Segmentation of the millipede trunk as suggested by a homeotic mutant with six
      extra pairs of gonopods.
AB  - BACKGROUND: The mismatch between dorsal and ventral trunk features along the
      millipede trunk was long a subject of controversy, largely resting on alternative
      interpretations of segmentation. Most models of arthropod segmentation presuppose
      a strict sequential antero-posterior specification of trunk segments, whereas
      alternative models involve the early delineation of a limited number of 'primary
      segments' followed by their sequential stereotypic subdivision into 2n definitive
      segments. The 'primary segments' should be intended as units identified by
      molecular markers, rather than as overt morphological entities. Two predictions
      were suggested to test the plausibility of multiple-duplication models of
      segmentation: first, a specific pattern of evolvability of segment number in
      those arthropod clades in which segment number is not fixed (e.g., epimorphic
      centipedes and millipedes); second, the occurrence of discrete multisegmental
      patterns due to early, initially contiguous positional markers. RESULTS: We
      describe a unique case of a homeotic millipede with 6 extra pairs of ectopic
      gonopods replacing walking legs on rings 8 (leg-pairs 10-11), 15 (leg-pairs 24
      25) and 16 (leg-pairs 26-27); we discuss the segmental distribution of these
      appendages in the framework of alternative models of segmentation and present an
      interpretation of the origin of the distribution of the additional gonopods.The
      anterior set of contiguous gonopods (those normally occurring on ring 7 plus the
      first set of ectopic ones on ring 8) is reiterated by the posterior set (on rings
      15-16) after exactly 16 leg positions along the AP body axis. This suggests that
      a body section including 16 leg pairs could be a module deriving from 4 cycles of
      regular binary splitting of an embryonic 'primary segment'. CONCLUSIONS: A very
      likely early determination of the sites of the future metamorphosis of walking
      legs into gonopods and a segmentation process according to the multiplicative
      model may provide a detailed explanation for the distribution of the extra
      gonopods in the homeotic specimen. The hypothesized steps of segmentation are
      similar in both a normal and the studied homeotic specimen. The difference
      between them would consist in the size of the embryonic trunk region endowed with
      a positional marker whose presence will later determine the replacement of
      walking legs by gonopods.

PMID- 24438179
TI  - Genetic architecture of spring and autumn phenology in Salix.
AB  - BACKGROUND: In woody plants from temperate regions, adaptation to the local
      climate results in annual cycles of growth and dormancy, and optimal regulation
      of these cycles are critical for growth, long-term survival, and competitive
      success. In this study we have investigated the genetic background to growth
      phenology in a Salix pedigree by assessing genetic and phenotypic variation in
      growth cessation, leaf senescence and bud burst in different years and
      environments. A previously constructed linkage map using the same pedigree and
      anchored to the annotated genome of P. trichocarpa was improved in target regions
      and used for QTL analysis of the traits. The major aims in this study were to map
      QTLs for phenology traits in Salix, and to identify candidate genes in QTL hot
      spots through comparative mapping with the closely related Populus trichocarpa.
      RESULTS: All traits varied significantly among genotypes and the broad-sense
      heritabilities ranged between 0.5 and 0.9, with the highest for leaf senescence.
      In total across experiment and years, 80 QTLs were detected. For individual
      traits, the QTLs explained together from 21.5 to 56.5% of the variation.
      Generally each individual QTL explained a low amount of the variation but three
      QTLs explained above 15% of the variation with one QTL for leaf senescence
      explaining 34% of the variation. The majority of the QTLs were recurrently
      identified across traits, years and environments. Two hotspots were identified on
      linkage group (LG) II and X where narrow QTLs for all traits co-localized.
      CONCLUSIONS: This study provides the most detailed analysis of QTL detection for
      phenology in Salix conducted so far. Several hotspot regions were found where
      QTLs for different traits and QTLs for the same trait but identified during
      different years co-localised. Many QTLs co-localised with QTLs found in poplar
      for similar traits that could indicate common pathways for these traits in
      Salicaceae. This study is an important first step in identifying QTLs and
      candidate genes for phenology traits in Salix.

PMID- 24438180
TI  - Aging theories and the zero-sum game.

PMID- 24438182
TI  - Genotypic variation in the ability of landraces and commercial cereal varieties
      to avoid manganese deficiency in soils with limited manganese availability: is
      there a role for root-exuded phytases?
AB  - The marginal agricultural-systems of the Machair in the Western Isles of Scotland
      often have limited micronutrient availability because of alkaline soils.
      Traditional landraces of oats, barley and rye are thought to be better adapted to
      cope with the limited manganese (Mn) availability of these soils. When commercial
      cultivars are grown on the Machair, limited Mn-availability reduces crop yield
      and quality. We hypothesised that traditional cereal landraces selected on the
      Machair acquire Mn more effectively and that this could be linked to exudation of
      phytase from roots which would release Mn complexed with inositol phosphates.
      Growth and Mn-acquisition of five landraces and three commercial cultivars of
      barley and oats were determined in Machair soil. In addition, root phytase
      activities were assayed under Mn-starvation and sufficiency in hydroponics. In
      Machair soil, landraces had greater capacity for acquiring Mn and a greater
      ability to achieve maximum yield compared to the commercial cultivars. Under Mn
      starvation, root phytase exudation was upregulated in all plants, suggesting that
      this trait might allow cereals to acquire more Mn when Mn-availability is
      limited. In the landraces, exuded phytase activity related positively to relative
      Mn-accumulation, whereas in the commercial cultivars this relationship was
      negative, suggesting that this trait may be secondary to an efficiency trait that
      has been lost from commercial germplasm by breeding. This research shows that
      cereal landraces possess traits that could be useful for improving the Mn
      acquisition of commercial varieties. Exploiting the genetic diversity of
      landraces could improve the sustainability of agriculture on marginal calcareous
      lands globally. 

PMID- 24438183
TI  - Identification of interferon-gamma as a new molecular target of liver X receptor.
AB  - LXR (liver X receptor) is a ligand-activated transcription factor and plays an
      important role in regulation of lipid homoeostasis and inflammation. Several
      studies indicate that LXR inhibits IFN-gamma (interferon gamma)-induced
      biological responses; however, the influence of LXR on IFN-gamma expression has
      not been fully elucidated. In the present study, we investigated the effects of
      LXR activation on IFN-gamma expression at different levels. At the molecular
      level, we surprisingly observed that LXR ligand (T0901317) induced macrophage and
      T-cell IFN-gamma protein expression which was associated with increased mRNA and
      secreted protein levels in culture medium. In contrast, selective inhibition of
      LXRalpha and/or LXRbeta expression by siRNA reduced IFN-gamma expression.
      Promoter analysis defined the multiple LXREs (LXR-responsive elements) in the
      proximal region of the IFN-gamma promoter. EMSAs and ChIP indicated that LXR
      activation enhanced the binding of LXR protein to these LXREs. In vivo, T0901317
      increased wild-type mouse serum IFN-gamma levels and IFN-gamma expression in the
      lung and lymph nodes. Functionally, we observed that administration of T0901317
      to wild-type mice increased rates of survival and being tumour-free, and
      inhibited tumour growth when the animals were inoculated with LLC1 carcinoma. In
      contrast, these protective effects were substantially attenuated in IFN-gamma
      knockout (IFN-gamma-/-) mice, suggesting that the induction of IFN-gamma
      production plays a critical role in T0901317-inhibited tumour growth. Taken
      together, the results of the present study show that IFN-gamma is another
      molecular target of LXR activation, and it suggests a new mechanism by which LXR
      inhibits tumour growth. 

PMID- 24438184
TI  - Proximal nail fold flap dissection for digital myxoid cysts - a seven year
      experience.

PMID- 24438181
TI  - Cannabis controversies: how genetics can inform the study of comorbidity.
AB  - AIMS: To review three key and controversial comorbidities of cannabis use-other
      illicit drug use, psychosis and depression, as well as suicide, from a
      genetically informed perspective. DESIGN: Selective review. RESULTS: Genetic
      factors play a critical role in the association between cannabis use,
      particularly early-onset use and use of other illicit drugs, psychosis and
      depression, as well as suicide, albeit via differing mechanisms. For other
      illicit drugs, while there is strong evidence for shared genetic influences,
      residual association that is attributable to causal or person-specific
      environmental factors cannot be ruled out. For depression, common genetic
      influences are solely responsible for the association with cannabis use but for
      suicidal attempt, evidence for person-specific factors persists. Finally, even
      though rates of cannabis use are inordinately high in those with psychotic
      disorders, there is no evidence of shared genetic etiologies underlying this
      comorbidity. Instead, there is limited evidence that adolescent cannabis use
      might moderate the extent to which diathesis influences psychosis. CONCLUSIONS:
      Overlapping genetic influences underlie the association between early-onset
      cannabis use and other illicit drug use as well as depression and suicide. For
      psychosis, mechanisms other than shared genetic influences might be at play.

PMID- 24438185
TI  - Rhodobacter sphaeroides, a novel tumor-targeting bacteria that emits natural near
      infrared fluorescence.
AB  - Several optical imaging techniques have been used to monitor bacterial tropisms
      for cancer. Most such techniques require genetic engineering of the bacteria to
      express optical reporter genes. This study investigated a novel tumor-targeting
      strain of bacteria, Rhodobacter sphaeroides 2.4.1 (R. sphaeroides), which
      naturally emits near-infrared fluorescence, thereby facilitating the
      visualization of bacterial tropisms for cancer. To determine the penetration
      depth of bacterial fluorescence, various numbers of cells (from 10(8) to 10(10) 
      CFU) of R. sphaeroides and two types of Escherichia coli, which stably express
      green fluorescent protein (GFP) or red fluorescent protein (RFP), were injected
      s.c. or i.m. into mice. Bacterial tropism for cancer was determined after i.v.
      injection of R. sphaeroides (10(8)  CFU) into mice implanted s.c. with eight
      types of tumors. The intensity of the fluorescence signal in deep tissue (muscle)
      from R. sphaeroides was much stronger than from E. coli-expressing GFP or RFP.
      The near-infrared fluorescence signal from R. sphaeroides was visualized clearly
      in all types of human or murine tumors via accumulation of bacteria. Analyses of
      C-reactive protein and procalcitonin concentrations and body weights indicated
      that i.v. injection of R. sphaeroides does not induce serious systemic immune
      reactions. This study suggests that R. sphaeroides could be used as a tumor
      targeting microorganism for the selective delivery of drugs to tumor tissues
      without eliciting a systemic immune reaction and for visualizing tumors. 

PMID- 24438186
TI  - Hsp90-dependent regulatory circuitry controlling temperature-dependent fungal
      development and virulence.
AB  - The pathogenic fungi Candida albicans, Aspergillus fumigatus, and Cryptococcus
      neoformans are an increasing cause of human mortality, especially in
      immunocompromised populations. During colonization and adaptation to various host
      environments, these fungi undergo morphogenetic alterations that allow for
      survival within the host. One key environmental cue driving morphological changes
      is external temperature. The Hsp90 chaperone protein provides one mechanism to
      link temperature with the signalling cascades that regulate morphogenesis, fungal
      development and virulence. Candida albicans is a model system for understanding
      the connections between morphogenesis and Hsp90. Due to the high degree of
      conservation in Hsp90, many of the connections in C. albicans may be extrapolated
      to other fungal pathogens or parasites. Examining the role of Hsp90 during
      development and morphogenesis in these three major fungal pathogens may provide
      insight into key aspects of adaptation to the host, leading to additional avenues
      for therapy. 

PMID- 24438188
TI  - Short-term type-1 diabetes differentially modulates 14-3-3 proteins in rat brain
      and liver.
AB  - BACKGROUND: The 14-3-3 proteins family consists of seven proteins that are highly
      conserved molecular chaperones with roles in the regulation of metabolism, signal
      transduction, cell cycle control, protein trafficking and apoptosis. Their role
      in several pathologies has been reported. In this study, we investigated the mRNA
      and protein expression of the 14-3-3s in rat brain and liver in the early stage
      of Type-1 diabetes (T1D). MATERIAL AND METHODS: Diabetes was induced by a single
      intraperitoneal injection (70 mg/kg bw) of freshly prepared streptozotocin (STZ),
      and, after 3 weeks of treatment, brain and liver nuclei and cytosolic extracts
      were prepared. Quantitative real-time PCR and Western blotting analyses were
      performed to evaluate mRNA and protein expression for each of the seven 14-3-3s.
      RESULTS: In nondiabetic control rats, the expression profile of 14-3-3s revealed
      a tissue-specific distribution, and the expression level of each isoform was
      found higher in the brain than in the liver. In the diabetic brain, mRNA and
      protein levels of the 14-3-3beta, epsilon, zeta, eta and theta were lower; 14-3
      3sigma mRNA significantly increased while its protein level decreased. In the
      diabetic liver, the mRNA of 14-3-3gamma, 14-3-3theta and 14-3-3sigma
      significantly increased, but only the 14-3-3gamma protein level increased.
      Overall, in diabetic animals, the changes in the expression levels of brain 14-3
      3s were much more pronounced than in the liver. CONCLUSION: Our results indicate
      that during the early phase of STZ-induced T1D, the 14-3-3 proteins are affected
      in an isoform- and tissue-specific way.

PMID- 24438189
TI  - Determination of volatile organic compounds and associated health risk assessment
      in residential homes and hostels within an academic institute, New Delhi.
AB  - The purpose of this study was to investigate the concentrations of volatile
      organic compounds (VOCs) in different indoor microenvironments of residential
      homes and hostels in an academic institute, in New Delhi, during March-May 2011.
      Eleven VOCs (aromatic and halogenated) were assessed. Sampling and analytical
      procedure were based on National Institute for Occupational Safety and Health
      (NIOSH) standard method. The lifetime cancer and non-cancer risk were calculated
      for targeted VOCs using US Environmental Protection Agency guidelines. The mean
      concentrations of ? VOCs (sum of monitored VOCs) and individual VOC were found to
      be higher indoors as compared to outdoors at both types of premises. Indoor to
      outdoor (I/O) ratios of the targeted VOCs exceeded 1.0, suggesting the
      significant presence of indoor sources. Strong correlations between I/O
      concentrations of VOCs in the current study suggest the presence of common
      sources. Factor analysis (FA) was used for source evaluation separately at two
      premise types. The estimated lifetime cancer risks in the current study for all
      occupants at both premises exceeded 10(-6) . 

PMID- 24438190
TI  - Shelf life stability of lactobacilli encapsulated in raspberry powder: insights
      into non-dairy probiotics.
AB  - AIM: Study the shelf-life quality changes in raspberry juice with encapsulated
      lactobacilli (Lactobacillus rhamnosus NRRL B-4495 and Lactobacillus acidophilus
      NRRL B-442) obtained by spray drying and understand the various factors involved.
      METHODS AND RESULTS: Raspberry powder was obtained from spray drying lactobacilli
      and raspberry juice with maltodextrin as an additive. Shelf life of the powder
      was analyzed over a period of 30 d. Acid and bile tolerance and antibiotic
      resistance was compared before and after spray drying. Water activity, survival,
      and scanning electron microscope images were also measured during the shelf life.
      CONCLUSIONS AND SIGNIFICANCE: A combination of processing conditions: inlet
      temperature ( degrees C), maltodextrin to juice solids ratio and inlet feed rate
      (ml/min) during spray drying had a significant role on the survival of
      lactobacilli during shelf life. Refrigerated storage provided a higher shelf-life
      stability with regards to CFU/g (as high as 84% on day 0 and 98% retention by the
      end of 30 d) compared to room temperature storage. Probiotic properties during
      shelf life are affected by the processing conditions and encapsulated food
      matrix. Thus, understanding these aspects in vitro during shelf life gives us a
      brief insight into the future of non-dairy probiotics.

PMID- 24438192
TI  - Serum pentraxin 3 concentrations in neonates.

PMID- 24438191
TI  - Metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse
      model is enhanced by L-plastin expression and phosphorylation.
AB  - BACKGROUND: Tumor cell migration and metastasis require dynamic rearrangements of
      the actin cytoskeleton. Interestingly, the F-actin cross-linking and stabilizing
      protein L-plastin, originally described as a leukocyte specific protein, is
      aberrantly expressed in several non-hematopoietic malignant tumors. Therefore, it
      has been discussed as a tumor marker. However, systematic in vivo analyses of the
      functional relevance of L-plastin for tumor cell metastasis were so far lacking.
      METHODS: We investigated the relevance of L-plastin expression and
      phosphorylation by ectopical expression of L-plastin in human melanoma cells
      (MV3) and knock-down of endogenous L-plastin in prostate cancer (PC3M). The
      growth and metastatic potential of tumor cells expressing no L-plastin,
      phosphorylatable or non-phosphorylatable L-plastin was analyzed in a preclinical
      mouse model after subcutaneous and intracardial injection of the tumor cells.
      RESULTS: Knock-down of endogenous L-plastin in human prostate carcinoma cells led
      to reduced tumor cell growth and metastasis. Vice versa, and in line with these
      findings, ectopic expression of L-plastin in L-plastin negative melanoma cells
      significantly increased the number of metastases. Strikingly, the metastasis
      promoting effect of L-plastin was not observed if a non-phosphorylatable L
      plastin mutant was expressed. CONCLUSIONS: Our data provide the first in vivo
      evidence that expression of L-plastin promotes tumor metastasis and, importantly,
      that this effect depends on an additionally required phosphorylation of L
      plastin. In conclusion, these findings imply that for determining the importance
      of tumor-associated proteins like L-plastin a characterization of
      posttranslational modifications is indispensable.

PMID- 24438193
TI  - The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR
      223 in extranodal NK/T-cell lymphoma, nasal type.
AB  - BACKGROUND: The mechanism for inactivation of positive regulatory domain
      containing I (PRDM1), a newly identified tumour suppressor gene in extranodal
      NK/T-cell lymphoma, nasal type (EN-NK/T-NT) has not been well defined. The aim of
      the present study was to investigate the expression of PRDM1 in EN-NK/T-NT and
      analyse its downregulation by miRNAs. METHODS: PRDM1 and miRNA expression were
      evaluated in EN-NK/T-NT samples by immunohistochemical analysis, qRT-PCR, and in
      situ hybridisation. Luciferase assays were performed to verify the direct binding
      of miR-223 to the 3'-untranslated region of PRDM1 mRNA. In addition, the effect
      of miR-223 on PRDM1 expression was assessed in NK/T lymphoma cell lines by
      transfecting a miR-223 mimic or inhibitor to increase or decrease the effective
      expression of miR-223. Overall survival and failure-free survival in EN-NK/T-NT
      patients were analysed using Kaplan-Meier single-factor analysis and the log-rank
      test. RESULTS: Investigation of the downregulation of PRDM1 in EN-NK/T-NT cases
      revealed that PRDM1-positive staining might be a favourable predictor of overall
      survival and failure-free survival in EN-NK/T-NT patients. However, the negative
      staining of PRDM1 usually presented transcripts, suggesting a possible post
      transcriptional regulation. miR-223 and its putative target gene, PRDM1,
      exhibited opposite patterns of expression in EN-NK/T-NT tissues and cell lines.
      Moreover, PRDM1 was identified as a direct target gene of miR-223 by luciferase
      assays. The ectopic expression of miR-223 led to the downregulation of the PRDM1
      protein in the NK/T-cell lymphoma cell line, whereas a decrease in miR-223
      restored the level of PRDM1 protein. CONCLUSIONS: Our findings reveal that the
      downregulation of the tumour suppressor PRDM1 in EN-NK/T-NT samples is mediated
      by miR-223 and that PRDM1-positive staining might have prognostic value for
      evaluating the clinical outcome of EN-NK/T-NT patients.

PMID- 24438195
TI  - Moving beyond rituximab, cyclophosphamide, doxorubicin, vincristine and
      prednisone for diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin
      lymphoma (NHL). While the de facto treatment standard R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone) is curative in most
      cases, it is ineffective for a significant proportion of patients, particularly
      those with intermediate and high-risk disease. Efforts to improve upon the
      results of R-CHOP have principally explored dose intensification of chemotherapy
      and resulted in considerable additive toxicity without clear benefit. DLBCL is
      not a uniform disease, however, and can be dissected into distinct molecular
      subtypes by gene expression profiling. These subtypes are characterized by
      distinct oncogenic mechanisms of activation and addictions to aberrant
      intracellular signaling pathways. Novel therapeutic agents that target these
      pathway addictions are emerging, and may have specific activity within molecular
      subtypes of DLBCL. To move beyond R-CHOP for all patients with DLBCL, targeted
      therapies added to the most effective chemotherapy platforms must be studied
      within the context of molecularly defined subsets.

PMID- 24438194
TI  - The start of the transplant journey: referral for pediatric solid organ
      transplantation.
AB  - The focus of the majority of the psychosocial transplant literature is on post
      transplant outcomes, but the transplant journey starts much earlier than this, at
      the point when transplantation is first considered and a referral for transplant
      evaluation is made. In this review, we cover information regarding the meaning of
      the referral process for solid organ transplantation. We discuss various factors
      of the referral for transplantation including the impact of referral on the
      pediatric patient and the family, potential expectations and misconceptions held
      by pediatric patients and parents, the role of health literacy, decision-making
      factors, and the informational needs of pediatric patients and parents. We
      elucidate steps that providers can take to enhance transplant referral and
      provide suggestions for much needed research within this area. 

PMID- 24438196
TI  - Development of aggressive T-cell leukemia at 1 month after the diagnosis of
      hypereosinophilic syndrome.

PMID- 24438199
TI  - Endoscopic ventilation tube placement in the pediatric age.

PMID- 24438198
TI  - Down-regulation of acetolactate synthase compromises Ol-1- mediated resistance to
      powdery mildew in tomato.
AB  - BACKGROUND: In a cDNA-AFLP analysis comparing transcript levels between powdery
      mildew (Oidium neolycopersici)-susceptible tomato cultivar Moneymaker (MM) and
      near isogenic lines (NILs) carrying resistance gene Ol-1 or Ol-4, a transcript
      derived fragment (TDF) M11E69-195 was found to be present in NIL-Ol-1 but absent
      in MM and NIL-Ol-4. This TDF shows homology to acetolactate synthase (ALS). ALS
      is a key enzyme in the biosynthesis of branched-chain amino acids valine, leucine
      and isoleucine, and it is also a target of commercial herbicides. RESULTS: Three
      ALS homologs ALS1, ALS2, ALS3 were identified in the tomato genome sequence. ALS1
      and ALS2 show high similarity, whereas ALS3 is more divergent. Transient
      silencing of both ALS1 and ALS2 in NIL-Ol-1 by virus-induced gene silencing
      (VIGS) resulted in chlorotic leaf areas that showed increased susceptibility to
      O. neolycopersici (On). VIGS results were confirmed by stable transformation of
      NIL-Ol-1 using an RNAi construct targeting both ALS1 and ALS2. In contrast,
      silencing of the three ALS genes individually by RNAi constructs did not
      compromise the resistance of NIL-Ol-1. Application of the herbicide chlorsulfuron
      to NIL-Ol-1 mimicked the VIGS phenotype and caused loss of its resistance to On.
      Susceptible MM and On-resistant line NIL-Ol-4 carrying a nucleotide binding site
      and leucine rich repeat (NB-LRR) resistance gene were also treated with
      chlorsulfuron. Neither the susceptibility of MM nor the resistance of NIL-Ol-4
      was affected. CONCLUSIONS: ALS is neither involved in basal defense, nor in
      resistance conferred by NB-LRR type resistance genes. Instead, it is specifically
      involved in Ol-1-mediated resistance to tomato powdery mildew, suggesting that
      ALS-induced change in amino acid homeostasis is important for resistance
      conferred by Ol-1.

PMID- 24438197
TI  - Evolutionary classification of ammonium, nitrate, and peptide transporters in
      land plants.
AB  - BACKGROUND: Nitrogen uptake, reallocation within the plant, and between
      subcellular compartments involves ammonium, nitrate and peptide transporters.
      Ammonium transporters are separated into two distinct families (AMT1 and AMT2),
      each comprised of five members on average in angiosperms. Nitrate transporters
      also form two discrete families (NRT1 and NRT2), with angiosperms having four
      NRT2s, on average. NRT1s share an evolutionary history with peptide transporters
      (PTRs). The NRT1/PTR family in land plants usually has more than 50 members and
      contains also members with distinct activities, such as glucosinolate and
      abscisic acid transport. RESULTS: Phylogenetic reconstructions of each family
      across 20 land plant species with available genome sequences were supplemented
      with subcellular localization and transmembrane topology predictions. This
      revealed that both AMT families diverged prior to the separation of bryophytes
      and vascular plants forming two distinct clans, designated as supergroups, each.
      Ten supergroups were identified for the NRT1/PTR family. It is apparent that
      nitrate and peptide transport within the NRT1/PTR family is polyphyletic, that
      is, nitrate and/or peptide transport likely evolved multiple times within land
      plants. The NRT2 family separated into two distinct clans early in vascular plant
      evolution. Subsequent duplications occurring prior to the eudicot/monocot
      separation led to the existence of two AMT1, six AMT2, 31 NRT1/PTR, and two NRT2
      clans, designated as groups. CONCLUSION: Phylogenetic separation of groups
      suggests functional divergence within the angiosperms for each family. Distinct
      groups within the NRT1/PTR family appear to separate peptide and nitrate
      transport activities as well as other activities contained within the family, for
      example nitrite transport. Conversely, distinct activities, such as abscisic acid
      and glucosinolate transport, appear to have recently evolved from nitrate
      transporters.

PMID- 24438200
TI  - Bioeconomic model and selection indices in Aberdeen Angus cattle.
AB  - A bioeconomic model was developed to calculate economic values for biological
      traits in full-cycle production systems and propose selection indices based on
      selection criteria used in the Brazilian Aberdeen Angus genetic breeding
      programme (PROMEBO). To assess the impact of changes in the performance of the
      traits on the profit of the production system, the initial values of the traits
      were increased by 1%. The economic values for number of calves weaned (NCW) and
      slaughter weight (SW) were, respectively, R$ 6.65 and R$ 1.43/cow/year. The
      selection index at weaning showed a 44.77% emphasis on body weight, 14.24% for
      conformation, 30.36% for early maturing and 10.63% for muscle development. The
      eighteen-month index showed emphasis of 77.61% for body weight, 4.99% for
      conformation, 11.09% for early maturing, 6.10% for muscle development and 0.22%
      for scrotal circumference. NCW showed highest economic impact, and SW had
      important positive effect on the economics of the production system. The
      selection index proposed can be used by breeders and should contribute to greater
      profitability. 

PMID- 24438201
TI  - Urinary tract infection among obstetric fistula patients at Gondar University
      Hospital, northwest Ethiopia.
AB  - BACKGROUND: Many women die from complications related to pregnancy and
      childbirth. In developing countries particularly in sub-Saharan Africa and Asia,
      where access to emergency obstetrical care is often limited, obstetric fistula
      usually occurs as a result of prolonged obstructed labour. Obstetric fistula
      patients have many social and health related problems like urinary tract
      infections (UTIs). Despite this reality there was limited data on prevalence UTIs
      on those patients in Ethiopia. Therefore, the aim of this study was to determine
      the prevalence, drug susceptibility pattern and associated risk factors of UTI
      among obstetric fistula patients at Gondar University Hospital, Northwest
      Ethiopia. METHODS: A cross sectional study was conducted from January to May,
      2013 at Gondar University Hospital. From each post repair obstetric fistula
      patients, socio-demographic and UTIs associated risk factors were collected by
      using a structured questionnaire. After the removal of their catheters, the mid
      stream urine was collected and cultured on CLED. After overnight incubation,
      significant bacteriuria was sub-cultured on Blood Agar Plate (BAP) and MacConkey
      (MAC). The bacterial species were identified by series of biochemical tests.
      Antibiotic susceptibility test was done by disc diffusion method. Data was
      entered and analyzed by using SPSS version 20. RESULTS: A total of 53 post repair
      obstetric fistula patients were included for the determination of bacterial
      isolate and 28 (52.8%) of them had significant bacteriuria. Majority of the
      bacterial isolates, 26 (92.9%), were gram negative bacteria and the predominant
      ones were Citrobacter 13 (24.5%) and E. coli 6 (11.3%). Enterobacter, E.coli and
      Proteus mirabilis were 100% resistant to tetracycline. Enterobacter, Proteus
      mirabilis, Klebsella pneumonia, Klebsella ozenae and Staphylococcus aureus were
      also 100% resistant to ceftriaxone. CONCLUSION: The prevalence of bacterial
      isolates in obstetric fistula patients was high and majority of the isolates were
      gram negative bacteria. Even thought the predominant bacterial isolates were
      Citrobacter and E. coli, all of the bacterial isolates had multiple antibiotic
      resistance patterns which alert health profession to look better treatment for
      these patients.

PMID- 24438202
TI  - Center-of-pressure total trajectory length is a complementary measure to maximum
      excursion to better differentiate multidirectional standing limits of stability
      between individuals with incomplete spinal cord injury and able-bodied
      individuals.
AB  - BACKGROUND: Sensorimotor impairments secondary to a spinal cord injury affect
      standing postural balance. While quasi-static postural balance impairments have
      been documented, little information is known about dynamic postural balance in
      this population. The aim of this study was to quantify and characterize dynamic
      postural balance while standing among individuals with a spinal cord injury using
      the comfortable multidirectional limits of stability test and to explore its
      association with the quasi-static standing postural balance test. METHODS:
      Sixteen individuals with an incomplete spinal cord injury and sixteen able-bodied
      individuals participated in this study. For the comfortable multidirectional
      limits of stability test, participants were instructed to lean as far as possible
      in 8 directions, separated by 45 degrees  while standing with each foot on a
      forceplate and real-time COP visual feedback provided. Measures computed using
      the center of pressure (COP), such as the absolute maximal distance reached
      (COPmax) and the total length travelled by the COP to reach the maximal distance
      (COPlength), were used to characterize performance in each direction. Quasi
      static standing postural balance with eyes open was evaluated using time-domain
      measures of the COP. The difference between the groups and the association
      between the dynamic and quasi-static test were analyzed. RESULTS: The COPlength
      of individuals with SCI was significantly greater (p <= 0.001) than that of able
      bodied individuals in all tested directions except in the anterior and posterior
      directions (p <= 0.039), indicating an increased COP trajectory while progressing
      towards their maximal distance. The COPmax in the anterior direction was
      significantly smaller for individuals with SCI. Little association was found
      between the comfortable multidirectional limits of stability test and the quasi
      static postural balance test (r >= -0.658). CONCLUSION: Standing dynamic postural
      balance performance in individuals with an incomplete spinal cord injury can be
      differentiated from that of able-bodied individuals with the comfortable limits
      of stability test. Performance among individuals with an incomplete spinal cord
      injury is characterized by lack of precision when reaching. The comfortable
      limits of stability test provides supplementary information and could serve as an
      adjunct to the quasi-static test when evaluating postural balance in an
      incomplete spinal cord injury population.

PMID- 24438203
TI  - Open-label, multicenter study of self-administered icatibant for attacks of
      hereditary angioedema.
AB  - BACKGROUND: Historically, treatment for hereditary angioedema (HAE) attacks has
      been administered by healthcare professionals (HCPs). Patient self-administration
      could reduce delays between symptom onset and treatment, and attack burden. The
      primary objective was to assess the safety of self-administered icatibant in
      patients with HAE type I or II. Secondary objectives included patient convenience
      and clinical efficacy of self-administration. METHODS: In this phase IIIb, open
      label, multicenter study, adult patients were trained to self-administer a single
      30-mg icatibant subcutaneous injection to treat their next attack. Icatibant
      naive patients were treated by an HCP prior to self-administration. Evaluations
      included adverse event (AE) reporting, a validated questionnaire for convenience,
      and visual analog scale for efficacy. RESULTS: A total of 151 patients were
      enrolled; 104 had an attack requiring treatment during the study, and 97 patients
      (19 naive) were included in the self-administration cohort. Recurrence or
      worsening of HAE symptoms (22 of 97) was the most commonly reported AE; rescue
      medications including icatibant (N = 3) and C1-inhibitor concentrate (N = 6) were
      used in 13 cases. Overall, 89 of 97 patients used a single injection of
      icatibant. No serious AEs or hospitalizations were reported. Most patients
      (91.7%) found self-administration preferable to administration in the clinic. The
      median time to symptom relief (3.8 h) was comparable with results from controlled
      trials of icatibant. CONCLUSIONS: With appropriate training, patients were
      successfully able to recognize HAE attacks and decide when to self-administer
      icatibant. This, coupled with the patient-reported high degree of satisfaction,
      convenience and ease of use supports the adoption of icatibant self
      administration in clinical practice.

PMID- 24438205
TI  - The rediscovery of smallpox.
AB  - Smallpox is an infectious disease that is unique to humans, caused by a poxvirus.
      It is one of the most lethal of diseases; the virus variant Variola major has a
      mortality rate of 30%. People surviving this disease have life-long consequences,
      but also assured immunity. Historically, smallpox was recognized early in human
      populations. This led to prevention attempts--variolation, quarantine, and the
      isolation of infected subjects--until Jenner's discovery of the first steps of
      vaccination in the 18th century. After vaccination campaigns throughout the 19th
      and 20th centuries, the WHO declared the eradication of smallpox in 1980. With
      the development of microscopy techniques, the structural characterization of the
      virus began in the early 20th century. In 1990, the genomes of different smallpox
      viruses were determined; viruses could be classified in order to investigate
      their origin, diffusion, and evolution. To study the evolution and possible re
      emergence of this viral pathogen, however, researchers can only use viral genomes
      collected during the 20th century. Cases of smallpox in ancient periods are
      sometimes well documented, so palaeomicrobiology and, more precisely, the study
      of ancient smallpox viral strains could be an exceptional opportunity. The
      analysis of poxvirus fragmented genomes could give new insights into the genetic
      evolution of the poxvirus. Recently, small fragments of the poxvirus genome were
      detected. With the genetic information obtained, a new phylogeny of smallpox
      virus was described. The interest in conducting studies on ancient strains is
      discussed, in order to explore the natural history of this disease.

PMID- 24438206
TI  - Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory
      gene expression in lungs of humans with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex disease, the
      pathogenesis of which remains incompletely understood. Colonization with
      Pneumocystis jirovecii may play a role in COPD pathogenesis; however, the
      mechanisms by which such colonization contributes to COPD are unknown. The
      objective of this study was to determine lung gene expression profiles associated
      with Pneumocystis colonization in patients with COPD to identify potential key
      pathways involved in disease pathogenesis. Using COPD lung tissue samples made
      available through the Lung Tissue Research Consortium (LTRC), Pneumocystis
      colonization status was determined by nested PCR. Microarray gene expression
      profiles were performed for each sample and the profiles of colonized and non
      colonized samples compared. Overall, 18 participants (8.5%) were Pneumocystis
      colonized. Pneumocystis colonization was associated with fold increase in
      expression of four closely related genes: INF-gamma and the three chemokine
      ligands CXCL9, CXCL10, and CXCL11. These ligands are chemoattractants for the
      common cognate receptor CXCR3, which is predominantly expressed on activated Th1
      T-lymphocytes. Although these ligand-receptor pairs have previously been
      implicated in COPD pathogenesis, few initiators of ligand expression and
      subsequent lymphocyte trafficking have been identified: our findings implicate
      Pneumocystis as a potential trigger. The finding of upregulation of these
      inflammatory genes in the setting of Pneumocystis colonization sheds light on
      infectious-immune relationships in COPD. 

PMID- 24438208
TI  - Reconstruction of scalp wounds with exposed calvarium using a local flap and a
      split-thickness skin graft: case series of 20 patients.
AB  - OBJECTIVES: To describe the design, execution, outcomes, and advantages of a
      combined flap and split-thickness skin graft reconstructive technique for the
      repair of wounds of the scalp with exposed bone after Mohs micrographic surgery.
      MATERIALS AND METHODS: An analysis of the combined flap and graft technique of 20
      scalp defects ranging in size from 6.25 to 37.6 cm(2) is provided. Surgical
      defects and patient characteristics are described. Follow-up information is
      reviewed, and complications and final aesthetic results are reported. RESULTS:
      Twenty patients with 20 tumors on the scalp (16 squamous cell carcinoma, 2 basal
      cell carcinoma, 1 Merkel cell carcinoma, and 1 malignant fibrous histiocytoma)
      were treated using Mohs micrographic surgery. A combined flap and graft technique
      was successfully employed with good aesthetic outcomes in all 20 patients with
      broad scalp defects. One postoperative complication of approximately 20% skin
      graft necrosis was noted. One methicillin-resistant Staphylococcus aureus
      postoperative wound infection occurred but resolved without sequelae with
      appropriate antibiotic treatment. CONCLUSION: The described flap and graft
      reconstructive technique is a reproducible, one-stage procedure for the
      reconstruction of medium to large scalp defects with exposed bone, obviating the
      need for more-complicated, costly, time-consuming procedures. LIMITATIONS: Small
      sample size, descriptive study.

PMID- 24438207
TI  - Implication of human herpesviruses in oncogenesis through immune evasion and
      supression.
AB  - All human herpesviruses (HHVs) have been implicated in immune system evasion and
      suppression. Moreover, two HHV family members, i.e. EBV and KSHV, are recognised
      as oncogenic viruses. Our literature review summarises additional examples of
      possible oncogenic mechanisms that have been attributed to other HHVs. In
      general, HHVs affect almost every cancer-implicated branch of the immune system,
      namely tumour-promoting inflammation, immune evasion, and immunosuppression. Some
      HHVs accomplish these effects by inhibiting apoptotic pathways and by promoting
      proliferation. Mechanisms related to immunosupression and low grade chronic
      inflammation could eventually result in the initiation and progression of cancer.
      In this article we open a discussion on the members of Herpesviridae, their
      immune evasion and suppression mechanisms, and their possible role in cancer
      development. We conclude that discerning the mechanisms of interplay between HHV,
      immune system, and cancer is essential for the development of novel preventative
      and therapeutic approaches for cancer treatment and prophylaxis. 

PMID- 24438209
TI  - Large vessel vasculitis and spondyloarthritis: coincidence or associated
      diseases?
AB  - INTRODUCTION: Although cardiac complications have been reported in established
      spondyloarthritis (SpA), little is known about peripheral axial SpA in large
      vessel vasculitis (LVV). The aim of this study was to assess the prevalence of
      SpA in patients with newly diagnosed LVV. METHOD: Retrospective single-centre
      analysis of all newly diagnosed LVV patients was performed between January 2011
      and December 2012. Vasculitides were confirmed on thoracic magnetic resonance
      imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT). Patients completed a standardized questionnaire
      incorporating the Berlin criteria to assess inflammatory back pain. Existing
      scans were reassessed for sacroiliitis and ferritin antibodies measured in all
      patients. RESULTS: Fifteen patients exhibiting new LVV were identified. Diagnosis
      was confirmed using MRI in nine patients and FDG-PET/CT in six. Six patients
      (40%) fulfilled American College of Rheumatology (ACR) criteria for giant cell
      arteritis (GCA) and polymyalgia rheumatica (PMR), and nine PMR only. Four
      patients fulfilled the Berlin criteria for inflammatory back pain, with three
      demonstrating sacroiliitis on imaging. All remaining patients demonstrated no
      sacroiliitis. One further patient with LVV lacking features of inflammatory back
      pain had known psoriatic arthritis (PsA). Patients with coexisting SpA were
      younger (mean age 57 years vs. 66 years) and had higher C-reactive protein (CRP)
      levels (200 mg/L vs. 85 mg/L) at presentation. Four SpA patients and seven out of
      nine patients with isolated LVV had ferritin antibodies. CONCLUSIONS: We have
      demonstrated a higher than anticipated prevalence of SpA in LVV, given the
      reported 0.5-1% prevalence in the general population. Coexisting SpA should be
      considered in LVV patients exhibiting inflammatory back pain despite steroid
      initiation. Ferritin antibodies demonstrated a similarly high prevalence in
      aortitis and SpA as reported previously in untreated GCA and PMR.

PMID- 24438210
TI  - Mental health of indigenous school children in Northern Chile.
AB  - BACKGROUND: Anxiety and depressive disorders occur in all stages of life and are
      the most common childhood disorders. However, only recently has attention been
      paid to mental health problems in indigenous children and studies of anxiety and
      depressive disorders in these children are still scarce. This study compares the
      prevalence of anxiety and depressive symptoms in Aymara and non-Aymara children.
      Among the Aymara children, the study examines the relations between these
      symptoms and the degree of involvement with Aymara culture. METHODS: We recruited
      748 children aged 9 to 15 years from nine schools serving low socioeconomic
      classes in the city of Arica, in northern Chile. The children were equally
      divided between boys and girls and 37% of the children were Aymara. To evaluate
      anxiety and depressive symptoms we used the Stress in Children (SiC) instrument
      and the Children Depression Inventory-Short version (CDI-S), and used an
      instrument we developed to assess level of involvement in the Aymara culture.
      RESULTS: There was no significant difference between Aymara and non-Aymara
      children on any of the instrument scales. Dividing the Aymara children into high
      involvement (n = 89) and low-involvement (n = 186) groups, the low-involvement
      group had significantly higher scores on the Hopelessness subscale of the CDI-S
      (p = 0.02) and scores of marginally higher significance in overall Anxiety on the
      SiC (p = 0.06). CONCLUSIONS: Although Aymara children have migrated from the high
      Andean plateau to the city, this migration has not resulted in a greater presence
      of anxiety and depressive symptoms. Greater involvement with the Aymara culture
      may be a protective factor against anxiety and depressive symptoms in Aymara
      children. This point to an additional benefit of maintaining cultural traditions
      within this population.

PMID- 24438211
TI  - Toxoplasma development - turn the switch on or off?
AB  - Toxoplasma gondii exhibits a complex, multi-stage life cycle in which the need
      for parasite expansion is balanced with the production of transmissible forms.
      For human disease the key developmental switch is from the tachyzoite to the
      mature bradyzoite, which is not well understood at the molecular level. This
      review highlights the role of the tachyzoite in regulating the initiation of
      bradyzoite differentiation through newly discovered transcription factors of the
      ApiAP2 family that must be turned off for development to unfold. Exit from the
      tachyzoite cell cycle is also tightly co-ordinated with the induction of
      bradyzoite gene expression, which is strongly influenced by the host cell
      environment. New evidence suggests a parasite casein kinase II and host anti
      growth factor CDA1 can influence specific pathways that are responsible for
      sensing the host cell environment and informing the parasites decision to
      continue replication or to develop into bradyzoites. These results indicate
      tachyzoite gene expression mechanisms and signal transduction pathways likely
      hold the keys to tissue cyst formation in Toxoplasma. 

PMID- 24438212
TI  - The dynamics of niche evolution upon abrupt environmental change.
AB  - Abrupt environmental changes are of particular interest to understand how species
      can quickly evolve at the boundary of their current niche. In particular the
      "sliding niche" model, wherein a niche shifts globally toward the new condition,
      has been used in understanding and modeling this process. Here, we investigate
      the dynamics of relative fitness change in four evolutionary replicates of
      Escherichia coli populations exposed to an extreme pH shift. We analyzed these
      changes at generations 500, 1000, and 2000 to determine whether niche global
      deformations fully capture the temporal dynamics of niche evolution. Strikingly,
      this analysis reveals that fitness variations can indeed be attributed to simple
      and global deformation of an underlying simple niche template. Analysis from two
      experimental replicates displays a transient increase in niche width, consistent
      with recent theory considering plasticity evolution in the context of an abrupt
      environmental change. We term this scenario the "sidestep niche model." 

PMID- 24438213
TI  - Glycemic index of American-grown jasmine rice classified as high.
AB  - The primary objective was to determine the glycemic index (GI) of jasmine rice
      grown in the United States (US). Secondary objective was to compare the GI of US
      grown jasmine rice to those grown in Thailand. Twelve healthy subjects were
      served all four brands of jasmine rice and a reference food (glucose), each
      containing 50 g of available carbohydrate. Fingerstick blood glucose was measured
      at 0, 15, 30, 45, 60, 90, and 120 min after consumption following a fasting
      state. The GI was calculated using the standard equation. The GI values for test
      foods ranged from 96 to 116 and were all classified as high GI foods. No
      difference in GI was found between American-grown and Thailand-grown jasmine
      rice. Although not statistically significant, observations show glycemic response
      among Asian American participants may be different. GI should be considered when
      planning meals with jasmine rice as the main source carbohydrate.

PMID- 24438214
TI  - Uniformity of stratum-ventilated thermal environment and thermal sensation.
AB  - Three human test series were conducted to evaluate the uniformity of the thermal
      environments in a stratum-ventilated chamber with dimensions of 8.8 m (L) * 5.1 m
      (W) * 2.4 m (H). In all, nineteen conditions were generated by adjusting the room
      temperature, supply airflow rate, and supply terminal type. An air diffuser
      performance index (ADPI) of at least 80% was achieved for most cases. This result
      shows that the air velocity and temperature in the occupied zone are reasonably
      uniform. Subjective assessments using the ASHRAE 7-point scale indicate that the
      thermal sensations of the subjects in stratum ventilation are also uniform. This
      study examines the applicability of the predicted mean vote (PMV) model for
      evaluating stratum ventilation. When compared to the actual mean thermal
      sensation votes (ATS), the PMV values are acceptable. The PMV results at a height
      of 1.1 m above the floor show better agreement with the ATS than at a height of
      0.1 m. 

PMID- 24438215
TI  - CYP3A5 genotypes affect tacrolimus pharmacokinetics and infectious complications
      in Chinese pediatric liver transplant patients.
AB  - Little information is available regarding the impact of cytochrome P450 (CYP) 3A5
      on the metabolism of TAC in infant LTx. Therefore, the CYP3A5 genotype of Chinese
      pediatric recipients (intestine) as well as donors (graft liver) was performed
      for the purpose of establishing an optimal dosage regimen in children. Sixty-four
      patients were divided according to CYP3A5 genotype (expression of *1 allele: EX
      and NEX) for each recipient (R) and donor (D), EX-R/EX-D (n = 21), EX-R/NEX-D (n
      = 8), NEX-R/EX-D (n = 8) and NEX-R/NEX-D (n = 27). Results indicated that initial
      TAC daily dose requirement was higher among EX-R/EX-D children compared with
      those who did not express CYP3A5 (0.28 +/- 0.10 vs. 0.19 +/- 0.08 mg/kg/day, p <
      0.01). CYP3A5 expression contributed an overall of 38.35% to its C/D ratios, and
      graft liver was a key determinant. Additionally, the EX-R/EX-D group showed
      significantly higher incidence of infectious complications, lower immune response
      and was an independent risk factor for the development of infections (odds ratio
      3.86, p = 0.025). Donor CYP3A5 expression partially explains TAC dose
      requirement, the effect of CYP3A5 variation may influence clinical outcomes;
      therefore, monitoring immune response may be important for preventing risks
      associated with under- and over-immunosuppression.

PMID- 24438216
TI  - The activation of c-Jun NH2-terminal kinase is required for dihydroartemisinin
      induced autophagy in pancreatic cancer cells.
AB  - BACKGROUND: c-Jun NH2-terminal kinases (JNKs) are strongly activated by a
      stressful cellular environment, such as chemotherapy and oxidative stress.
      Autophagy is a protein-degradation system in which double-membrane vacuoles
      called autophagosomes are formed. The autophagy-related gene Beclin 1 plays a key
      role in this process. We previously found that autophagy was induced by
      dihydroartemisinin (DHA) in pancreatic cancer cells. However, little is known
      about the complex relationship between ROS, JNK activation, autophagy induction,
      and Beclin 1 expression. METHODS: Cell viability and CCK-8 assays were carried
      out to determine the cell proliferation; small interfering RNAs (siRNAs) were
      used to knockdown c-Jun NH2-terminal kinases (JNK1/2) genes; western blot was
      performed to detect the protein expression of LC3, JNK, Beclin 1, caspase 3 and
      beta-actin; production of intracellular ROS was analyzed using FACS flow
      cytometry; autophagy induction was confirmed by electron microscopy. RESULTS: In
      the present study, we explored the role of DHA and Beclin 1 expression in
      autophagy. DHA-treated cells showed autophagy characteristics, and DHA also
      activated the JNK pathway and up-regulated the expression of Beclin 1.
      Conversely, blocking JNK signaling inhibited Beclin 1 up-regulation. JNK
      activation was found to primarily depend on reactive oxygen species (ROS)
      resulting from the DHA treatment. Moreover, JNK pathway inhibition and Beclin 1
      silencing prevented the induction of DHA-induced autophagy. CONCLUSIONS: These
      results suggest that the induction of autophagy by DHA is required for JNK
      mediated Beclin 1 expression.

PMID- 24438217
TI  - Transcriptome sequencing and phylogenomic resolution within Spalacidae
      (Rodentia).
AB  - BACKGROUND: Subterranean mammals have been of great interest for evolutionary
      biologists because of their highly specialized traits for the life underground.
      Owing to the convergence of morphological traits and the incongruence of
      molecular evidence, the phylogenetic relationships among three subfamilies
      Myospalacinae (zokors), Spalacinae (blind mole rats) and Rhizomyinae (bamboo
      rats) within the family Spalacidae remain unresolved. Here, we performed de novo
      transcriptome sequencing of four RNA-seq libraries prepared from brain and liver
      tissues of a plateau zokor (Eospalax baileyi) and a hoary bamboo rat (Rhizomys
      pruinosus), and analyzed the transcriptome sequences alongside a published
      transcriptome of the Middle East blind mole rat (Spalax galili). We characterize
      the transcriptome assemblies of the two spalacids, and recover the phylogeny of
      the three subfamilies using a phylogenomic approach. RESULTS: Approximately 50.3
      million clean reads from the zokor and 140.8 million clean reads from the bamboo
      ratwere generated by Illumina paired-end RNA-seq technology. All clean reads were
      assembled into 138,872 (the zokor) and 157,167 (the bamboo rat) unigenes, which
      were annotated by the public databases: the Swiss-prot, Trembl, NCBI non
      redundant protein (NR), NCBI nucleotide sequence (NT), Gene Ontology (GO),
      Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes
      (KEGG). A total of 5,116 nuclear orthologous genes were identified in the three
      spalacids and mouse, which was used as an outgroup. Phylogenetic analysis
      revealed a sister group relationship between the zokor and the bamboo rat, which
      is supported by the majority of gene trees inferred from individual orthologous
      genes, suggesting subfamily Myospalacinae is more closely related to subfamily
      Rhizomyinae. The same topology was recovered from concatenated sequences of 5,116
      nuclear genes, fourfold degenerate sites of the 5,116 nuclear genes and
      concatenated sequences of 13 protein coding mitochondrial genes. CONCLUSIONS:
      This is the first report of transcriptome sequencing in zokors and bamboo rats,
      representing a valuable resource for future studies of comparative genomics in
      subterranean mammals. Phylogenomic analysis provides a conclusive resolution of
      interrelationships of the three subfamilies within the family Spalacidae, and
      highlights the power of phylogenomic approach to dissect the evolutionary history
      of rapid radiations in the tree of life.

PMID- 24438218
TI  - Health related quality of life in Dutch young adults: psychometric properties of
      the PedsQL generic core scales young adult version.
AB  - BACKGROUND: The purpose of this study is to provide Dutch norm data and to assess
      internal consistency and construct validity for the Pediatric Quality of Life
      Inventory Young Adult Generic Core Scales (PedsQL_YA) in Dutch young adults aged
      18-30 years. METHODS: A sample of 649 young adults from the general Dutch
      population aged 18-30 years, stratified by age, sex, marital status and
      education, completed a socio-demographic questionnaire and the Dutch version of
      the PedsQL_YA online. Internal consistency of the PedsQL_YA scales was determined
      with Cronbach's alphas. Norm scores were obtained by calculating the mean PedsQL
      scale scores by gender, age and health status. Differences in scale scores were
      analyzed for gender, age and health status (construct validity) using two-sample
      t-tests and effect sizes were calculated. Construct validity was determined by
      testing differences in PedsQL scores between healthy young adults and young
      adults with chronic health conditions. RESULTS: All scales of the PedsQL_YA
      showed satisfactory to excellent internal consistency, with Cronbach's alphas
      between .77 and .94. Men reported higher scores (indicating better HRQOL) than
      women on all scales (p < .01), except for school/work functioning. No age
      differences were found. Young adults with chronic health conditions scored lower
      on all scales (p < .001) than healthy young adults, indicating good construct
      validity. Effect sizes varied from medium to large. CONCLUSIONS: The Dutch
      version of the PedsQL_YA has adequate psychometric properties. With the
      availability of reliable norm data, the PedsQL_YA can be used as a tool in the
      evaluation of health related quality of life in healthy young adults and those
      with a chronic health condition.

PMID- 24438219
TI  - Measuring outcome expectancy value of leisure-time physical activity for African
      Americans.
AB  - A scale was adapted from existing scales to measure the outcome expectancy value
      (EV) as one of contributory factors to leisure-time physical activity (LTPA) and
      was administered to 649 African American adults. The eligible participants (N =
      569) for the analysis were split into three subsamples (rate = 0.5 : 0.25 : 0.25)
      respectively for Exploratory Factor Analysis (N = 285) and cross-validation (N =
      142 for the calibration group and N = 142 for the validation group) to evaluate
      the psychometric properties of the scale. Item analysis of the scale provided
      adequate psychometric properties. The 2-factor solution with positive and
      negative outcome EV subscales was supported based on the exploratory factor
      analysis and the multiple-group confirmatory factor analysis for both the
      calibration and validation samples. The results support the factorial construct
      validity and criterion validity of the outcome EV scale applied to assess LTPA in
      a sample of church-going African Americans. 

PMID- 24438220
TI  - Laparoscopic vaginoplasty using a sigmoid graft through the umbilical single
      incision hybrid transperineal approach: our initial experience.
AB  - BACKGROUND: For better cosmetic appearance, attempts to reduce the number of
      laparoscopic wounds have been sought. Investigators have thus begun to carry out
      procedures through a single incision or natural orifice endoscopic surgery
      instead of using conventional laparoscopic surgery. The authors here describe
      transumbilical single-incision hybrid transperineal laparoscopic surgery as a
      novel approach for vaginoplasty using a sigmoid graft. PATIENTS AND METHODS: From
      August 2010 to October 2012, 15 young females with Mayer-Rokitansky-Kuster-Hauser
      (MRKH) syndrome underwent laparoscopic sigmoid vaginosplasty using a combined
      transumbilical single-incision and transperineal approach. A multichannel single
      port was placed through the umbilical incision for the main laparoscopic
      procedures. A 12-mm trocar as an assisting working port was inserted into the
      pelvic cavity through the transvaginal dimple between the rectum and urethra.
      RESULTS: A functioning vagina 12-15 cm in length and approximately 4 cm in width
      was created in all the patients. The average operative time and hospital stay
      were 151.5+/-34.2 minutes and 7.4+/-3.2 days, respectively. The only
      perioperative complications were 1 case of stress ulcer and 1 case with umbilical
      infection. All patients were satisfied with the surgery, and 12 of them had
      subsequent sexual activity. CONCLUSIONS: Transumbilical single-incision hybrid
      transperineal laparoscopic sigmoid vaginoplasty offers a feasible scarless
      approach for females with MRKH syndrome. The favorable cosmetic results would
      favor use of this type of vaginoplasty as an alternative to the conventional
      laparoscopic approach.

PMID- 24438221
TI  - Looking into the profile of those who succeed in losing weight with an
      intragastric balloon.
AB  - BACKGROUND: Weight loss by means of an intragastric balloon is an advantageous
      procedure, as usage of such a balloon is minimally invasive and of minimal
      operational risk. Nevertheless, despite the encouraging results referred in to
      large population studies, its success rate as a treatment option is still
      questionable. The aim of this study was to classify and analyze all parameters
      recorded in a database of a treatment protocol concerning obese individuals
      handled by an intragastric balloon, in an attempt to delineate the comparable
      profile of those who succeeded to lose weight and those who failed. SUBJECTS AND
      METHODS: Retrospective data collection, including demographic and anthropometric
      data, social and psychological factors, educational status, and attendance at
      sessions and the exercise program, was conducted. Using as a criterion for
      grouping the percentage of excess weight loss (%EWL), the successful (%EWL >=50%)
      and the poor (%EWL <=20%) responders were identified. RESULTS: In total, 583
      patients were assessed. Initial and ideal body weight (BW), initial body mass
      index (BMI), and excess weight were significantly lower in the %EWL >=50% group
      (P<.001). Upon balloon removal, both groups exhibited a significant difference
      regarding BW, BW lost, BMI, and %EWL (P<.001). Advanced age (odds ratio
      [OR]=1.06; P<.001), female gender (OR=3.31; P<.001), basic educational level
      (OR=3.12; P<.001), and single or divorced marital status (OR=6.00; P<.001) were
      identified as the most powerful determinants of %EWL >=50%. Moreover, attendance
      at more than four monthly interviews and strict exercise program commitment
      contributed significantly to a favorable outcome. CONCLUSIONS: Our findings could
      serve as an initial step for further research into factors possibly contributing
      to the early identification of those individuals who will notably benefit from
      usage of an intragastric balloon regarding BW loss.

PMID- 24438222
TI  - Implementation of an intensive short-term dynamic treatment program for patients
      with treatment-resistant disorders in residential care.
AB  - BACKGROUND: This protocol presents a systematic residential treatment- and
      research program aimed at patients who have not responded adequately to previous
      treatment attempts. Patients included in the program primarily suffer from
      anxiety and/or depressive disorders and usually from one or more comorbid
      personality disorders. The treatment program is time-limited (eight weeks) and
      has its basis in treatment principles specified in intensive short-term dynamic
      psychotherapy (ISTDP). This treatment modality is theoretically well-suited for
      the handling of various forms of treatment resistance presumably central to these
      patients' previous non-response to psychological and psychiatric interventions.
      METHODS/DESIGN: The research component of the project entails a naturalistic
      longitudinal research design which aims at systematic evaluation of the
      effectiveness of the program. To our knowledge, this is one of the first
      treatment programs and corresponding research projects that systematically select
      patients with previous non- or negative response to treatment and subjects them
      to a broad and comprehensive, but theoretically unified and consistent treatment
      system. DISCUSSION: The present paper introduces the project, describes its
      theoretical and methodological underpinnings, and discusses possible future
      implications and contributions of the project. It thereby serves as a
      comprehensive background reference to future publications from the project.

PMID- 24438225
TI  - Post Melody valve implant in a conduit with regurgitant native outflow tract
      successful closure by Amplatzer muscular device.
AB  - We describe the technique of closure of native right ventricular outflow tract by
      Amplatzer muscular ventricular septal defect device because of severe
      regurgitation in a patient who had tetralogy of Fallot repair with conduit at 3
      years of age followed by percutaneous Melody valve implant 6 years later. 

PMID- 24438223
TI  - CD4+CD25+ T regulatory cells activated during feline immunodeficiency virus
      infection convert T helper cells into functional suppressors through a membrane
      bound TGFbeta / GARP-mediated mechanism.
AB  - BACKGROUND: We and others have previously reported that cell membrane-bound
      TGFbeta (mTGFbeta) on activated T regulatory (Treg) cells mediates suppressor
      function. Current findings suggest that a novel protein known as Glycoprotein A
      Repetitions Predominant (GARP) anchors mTGFbeta to the Treg cell surface and
      facilitates suppressor activity. Recently, we have described that GARP+TGFbeta+
      Treg cells expand during the course of FIV infection. Because Treg cells are
      anergic and generally exhibit poor proliferative ability, we asked how Treg
      homeostasis is maintained during the course of feline immunodeficiency virus
      (FIV) infection. RESULTS: Here, we report that Treg cells from FIV+ cats express
      GARP and mTGFbeta and convert T helper (Th) cells into phenotypic and functional
      Treg cells. Th to Treg conversion was abrogated by anti-TGFbeta or anti-GARP
      treatment of Treg cells or by anti-TGFbetaRII treatment of Th cells, suggesting
      that Treg cell recruitment from the Th pool is mediated by TGFbeta/TGFbetaRII
      signaling and that cell-surface GARP plays a major role in this process.
      CONCLUSIONS: These findings suggest Th to Treg conversion may initiate a cascade
      of events that contributes to the maintenance of virus reservoirs, progressive Th
      cell immunosuppression, and the development of immunodeficiency, all of which are
      central to the pathogenesis of AIDS lentivirus infections.

PMID- 24438226
TI  - Everyday moral reasoning in the governmentality of HIV risk.
AB  - Drawing on the sociology of morality, this article analyses the social contexts,
      discourses and ethno-methods of everyday life that shape real-world decisions of
      gay men around HIV prevention. Through an analysis of the predominant narratives
      in an online public forum created for an HIV prevention campaign, this article
      explores the ways in which homosexually active men engage in everyday moral
      reasoning and challenge a neoliberal moral order of risk and responsibility. The
      article concludes that gay and bisexual men engage in forms of practical morality
      with their sexual partners and imagine larger communities of interest, love,
      companionship and pleasure. At the same time, they draw heavily from discourses
      on individual and rational responsibility, as well as narratives of romance and
      community, that shape forms of moral selfhood. Risk management techniques that
      are grounded in notions of rational choice and that are insensitive to the
      emotional worlds that these men inhabit create situations of risk avoidance but
      also inadvertently open them to new forms of vulnerability. 

PMID- 24438227
TI  - Comparison of two data collection processes in clinical studies: electronic and
      paper case report forms.
AB  - BACKGROUND: Electronic Case Report Forms (eCRFs) are increasingly chosen by
      investigators and sponsors of clinical research instead of the traditional pen
      and-paper data collection (pCRFs). Previous studies suggested that eCRFs avoided
      mistakes, shortened the duration of clinical studies and reduced data collection
      costs. METHODS: Our objectives were to describe and contrast both objective and
      subjective efficiency of pCRF and eCRF use in clinical studies. A total of 27
      studies (11 eCRF, 16 pCRF) sponsored by the Paris hospital consortium, conducted
      and completed between 2001 and 2011 were included. Questionnaires were emailed to
      investigators of those studies, as well as clinical research associates and data
      managers working in Paris hospitals, soliciting their level of satisfaction and
      preferences for eCRFs and pCRFs. Mean costs and timeframes were compared using
      bootstrap methods, linear and logistic regression. RESULTS: The total cost per
      patient was 374? +/-351 with eCRFs vs. 1,135? +/-1,234 with pCRFs. Time between
      the opening of the first center and the database lock was 31.7 months Q1 = 24.6;
      Q3 = 42.8 using eCRFs, vs. 39.8 months Q1 = 31.7; Q3 = 52.2 with pCRFs (p =
      0.11). Electronic CRFs were globally preferred by all (31/72 vs. 15/72 for paper)
      for easier monitoring and improved data quality. CONCLUSIONS: This study found
      that eCRFs and pCRFs are used in studies with different patient numbers, center
      numbers and risk. The first ones are more advantageous in large, low-risk studies
      and gain support from a majority of stakeholders.

PMID- 24438228
TI  - Osteopontin is up-regulated in chronic hepatitis C and is associated with
      cellular permissiveness for hepatitis C virus replication.
AB  - OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated
      during chronic liver injury and directly promotes fibrosis. We have reported that
      Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C
      virus)-infected cells. Hence we hypothesized that OPN directly promotes HCV
      replication, and that targeting OPN could be beneficial in HCV. In the present
      study, we compared the expression of OPN mRNA and protein in HCV (JFH1)-infected
      Huh7 and Huh7.5 cells, and evaluated whether modulating OPN levels using
      exogenous OPN ligands (up-regulate OPN) or OPN-specific RNA-aptamers (neutralize
      OPN) leads to changes in HCV expression. Sera and livers from patients with
      chronic HCV were analysed to determine whether OPN levels were associated with
      disease severity or response to therapy. Compared with Huh7 cells, Huh7.5 cells
      support higher levels of HCV replication (15-fold) and expressed significantly
      more OPN mRNA (30-fold) and protein. Treating Huh7 cells with OPN ligands led to
      a dose-related increase in HCV (15-fold) and OPN (8-fold) mRNA. Conversely,
      treating Huh7.5 cells with OPN-specific RNA aptamers inhibited HCV RNA and
      protein by >50% and repressed OPN mRNA to basal levels. Liver OPN expression was
      significantly higher (3-fold) in patients with advanced fibrosis. Serum OPN
      positively correlated with fibrosis-stage (P=0.009), but negatively correlated
      with ETBCR (end-of-treatment biochemical response), ETVR (end-of-treatment
      virological response), SBCR (sustained biochemical response) and SVR (sustained
      virological response) (P=0.007). The OPN fibrosis score (serum OPN and presence
      of fibrosis >=F2) may be a predictor of SVR. In conclusion, OPN is up-regulated
      in the liver and serum of patients with chronic hepatitis C, and supports
      increased viral replication. OPN neutralization may be a novel therapeutic
      strategy in chronic hepatitis C. 

PMID- 24438229
TI  - In-vitro evaluation of the tolerance of surgical instruments in templates for
      computer-assisted guided implantology produced by 3-D printing.
AB  - OBJECTIVE: The aim of this in-vitro study was to compare the tolerance of
      surgical instruments in surgical guides produced by 3-D printing, without metal
      sleeves to a surgical guide with conventional metal sleeves from two different
      manufacturers. MATERIALS AND METHODS: Lateral movements of drill tips caused by
      tolerance between the sleeve and drill key and between the drill key and the
      drill were recorded after application of a standardized force to the surgical
      instruments. Four groups were tested: Control 1 (C1): metal sleeve from
      commercially available surgical system 1; Test 1 (T1): 3-D-printed sleeve for
      surgical system 1; Control 2 (C2): metal sleeve from commercially available
      surgical system 2. Test 2 (T2): 3-D-printed sleeve for surgical system 2.
      RESULTS: The mean total lateral movement was 0.75 mm (0.5-1.04 mm) in the C1
      group and 0.91 mm (0.54-1.34 mm) in the C2 group. The mean amount of movement
      from tolerance between sleeve and drill-guiding key was 0.31 mm (range 0.22-0.41
      mm) in C1 and 0.42 mm (range 0.29-0.56 mm) in C2. This lateral movement was in
      mean reduced by 0.24 mm (32%) in T1 and by 0.39 mm (43%) in T2 group. This
      reduction was statistically significant in both groups (P < 0.001). CONCLUSION:
      The tolerance of surgical instruments and the lateral movements of the drills
      were significantly reduced by the use of 3-D printing with reduced sleeve
      diameter. This reduction could improve the overall accuracy in computer-assisted
      template-guided implant dentistry. The lateral movement of the drill can be
      further reduced by using a shorter drill and a higher drill key. This can be
      considered during implant planning and CAD/CAM of surgical guides.

PMID- 24438230
TI  - The emerging role of RNA-binding proteins in the life cycle of Trypanosoma
      brucei.
AB  - One of the key questions in understanding the biology of an organism is how to
      correlate cellular fate and function with gene expression patterns. This is
      particularly relevant for pathogenic organisms, like the parasitic protozoa
      Trypanosoma brucei, who often cycle between different hosts, thereby encountering
      vastly different environments. Survival in and adaptation to new surroundings
      requires activation of specific gene networks, which is most often achieved by
      regulatory mechanisms embedded in the transcriptional machinery. However, in T.
      brucei and related trypanosomatids these responses appear to be accomplished
      mainly by post-transcriptional mechanisms. Although an understanding of how this
      parasite modulates gene regulatory networks is in the early stages, RNA-binding
      proteins (RBPs) are beginning to take centre stage. Here, we discuss recent
      progress in the identification of RBPs with crucial roles in different stages of
      the T. brucei life cycle, and in elucidating targets of RBPs. 

PMID- 24438231
TI  - Physicochemical characterization and antioxidant activity of 17 commercial
      Moroccan honeys.
AB  - In this study, 17 commercial honey samples from Morocco were analyzed. Four
      samples did not meet the international physicochemical standards due to high
      hydroxymethylfurfural content and low diastase activity. Phenol content varied
      from 163.82 mg gallic acid equivalent (GAE)/kg in citrus honey to 923.70 mg
      (GAE)/kg in thyme honey from Rachidia; flavonoid content ranged from 4.26 mg
      quercetin equivalent (QE)/kg in citrus honey to 139.62 mg QE/kg in black cumin
      honey. Black cumin honey had the highest peroxyl scavenging activity; oregano
      (from Zaraphyt) and thyme honeys (from Rachidia) had the highest ABTS (2,2'-azino
      bis[3-ethylbenzothiazoline-6-sulphonic acid]) scavenging activity; and thyme
      honey (Saouira) had the highest NO scavenging capacity. The antioxidant activity
      of Moroccan honeys was correlated with the phenol, flavonoid, and melanoidin
      contents. Dark honeys had higher antioxidant activity than light honeys. Samples
      with high sodium levels had lower free radical scavenging activity. On the other
      hand, calcium and magnesium increased the ABTS and peroxyl scavenging capacity,
      respectively, of honey samples. According to cluster and discriminant analyses,
      the honey samples were grouped in three clusters with respect to the phenol,
      flavonoid, melanoidin, proline, mineral and sugar contents, and free radical
      scavenging capacity.

PMID- 24438233
TI  - A prospective study of non-surgical primary rhinoplasty using a
      polymethylmethacrylate injectable implant.
AB  - BACKGROUND: Nonsurgical rhinoplasty involves the use of injectable fillers to
      improve the contours of the nose. It has become a widely practiced procedure
      since this author first popularized it in 2003. The use of permanent fillers in
      nonsurgical rhinoplasty has not been well documented, especially in this country.
      OBJECTIVES: To demonstrate the safety and effectiveness of a
      polymethylmethacrylate (PMMA)-based filler for nonsurgical rhinoplasty. METHODS
      AND MATERIALS: Eligible subjects underwent up to three injection sessions with a
      commercially available PMMA product and were followed for 1 year. Efficacy was
      assessed according to evaluator grading of subjects and digital image analysis of
      standardized photographs. RESULTS: Nineteen subjects were enrolled and followed
      to conclusion. Average improvement in global score was more than one point
      observed on day 90 and lasting through 1 year. Eight of 10 subjects showed
      improvement according to digital image analysis at 1 year. Subject satisfaction
      was high throughout the study. Adverse events were minimal and well tolerated.
      CONCLUSION: Filler rhinoplasty using a PMMA-based injectable filler is safe and
      effective. This is the first study documenting the use of PMMA for this
      indication. Longer-term follow-up is needed to demonstrate persistence of
      improvement.

PMID- 24438234
TI  - Orodental status and medical problems of stroke inpatients undergoing
      rehabilitation at a rehabilitation hospital in Japan.
AB  - BACKGROUND AND OBJECTIVE: Many stroke patients may have oral problems and
      systemic diseases, but clinical information on treatment provided to stroke
      patients for dental problems during inpatient rehabilitation is rare. The
      objective of this study was to research stroke inpatients' requirements for
      dental treatment and the accompanying risks. METHODS: We included 165 stroke
      patients undergoing inpatient rehabilitation at Morinomiya Hospital during the
      year 2010 and researched the causes of stroke and the patients' orodental status,
      underlying diseases, antithrombotic drugs prescribed and special considerations
      or difficulties in the treatment. RESULTS: Cerebral infarction was the most
      common causes of stroke. Many patients had hypertension, heart disease or
      diabetes mellitus, and 54.5% had been prescribed antithrombotic drugs. Dentists
      diagnosed 57.0% patients with untreated dental cavities. Approximately 30% did
      not use dentures despite having a requirement. In total, 142 patients underwent
      dental treatment including periodontal treatment, prosthetic treatment and tooth
      extraction under management of circulation and haemostasis such as monitoring
      vital signs and surgical splints in cases of the difficult extraction.
      CONCLUSION: The current study revealed a high requirement for dental treatment
      among stroke patients and demonstrated the effectiveness of performing dental
      treatment during inpatient rehabilitation of these patients.

PMID- 24438232
TI  - Sex differences in the human peripheral blood transcriptome.
AB  - BACKGROUND: Genomes of men and women differ in only a limited number of genes
      located on the sex chromosomes, whereas the transcriptome is far more sex
      specific. Identification of sex-biased gene expression will contribute to
      understanding the molecular basis of sex-differences in complex traits and common
      diseases. RESULTS: Sex differences in the human peripheral blood transcriptome
      were characterized using microarrays in 5,241 subjects, accounting for menopause
      status and hormonal contraceptive use. Sex-specific expression was observed for
      582 autosomal genes, of which 57.7% was upregulated in women (female-biased
      genes). Female-biased genes were enriched for several immune system GO
      categories, genes linked to rheumatoid arthritis (16%) and genes regulated by
      estrogen (18%). Male-biased genes were enriched for genes linked to renal cancer
      (9%). Sex-differences in gene expression were smaller in postmenopausal women,
      larger in women using hormonal contraceptives and not caused by sex-specific
      eQTLs, confirming the role of estrogen in regulating sex-biased genes.
      CONCLUSIONS: This study indicates that sex-bias in gene expression is extensive
      and may underlie sex-differences in the prevalence of common diseases.

PMID- 24438235
TI  - Plague history: Yersin's discovery of the causative bacterium in 1894 enabled, in
      the subsequent century, scientific progress in understanding the disease and the
      development of treatments and vaccines.
AB  - The causative bacterium of plague was described and cultured by Alexandre Yersin
      in Hong Kong in 1894, after which transmission of bacteria from rodents by flea
      bites was discovered by Jean-Paul Simond in 1898. Effective treatment with
      antiserum was initiated in 1896, but this therapy was supplanted by sulphonamides
      in the 1930s and by streptomycin starting in 1947. India suffered an estimated 6
      million deaths in 1900-1909, and Vietnam, during its war in 1965-1975, accounted
      for approximately 80% of the world's cases; since then, African countries have
      dominated, with >90% of the world's cases in the 1990s and early 21st century.
      Serological diagnosis with fraction 1 antigen to detect anti-plague antibodies
      was developed in the 1950s. Vaccine development started in 1897 with killed whole
      bacterial cells, and this was followed by a live attenuated bacterial vaccine,
      leading to millions of persons receiving injections, but the benefits of these
      vaccines remain clouded by controversy. Plasmid-mediated virulence was
      established in 1981, and this was followed by specific DNA methods that have
      allowed detection of plague genes in skeletal specimens from European graves of
      the sixth to 17th centuries.

PMID- 24438236
TI  - The role of education in implementation science.

PMID- 24438239
TI  - The complete mitochondrial genome of the Feral Rock Pigeon (Columba livia breed
      feral).
AB  - Abstract In the present work, we report the complete mitochondrial genome
      sequence of feral rock pigeon for the first time. The total length of the
      mitogenome was 17,239 bp with the base composition of 30.3% for A, 24.0% for T,
      31.9% for C, and 13.8% for G and an A-T (54.3 %)-rich feature was detected. It
      harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes
      and 1 non-coding control region (D-loop region). The arrangement of all genes was
      identical to the typical mitochondrial genomes of pigeon. The complete
      mitochondrial genome sequence of feral rock pigeon would serve as an important
      data set of the germplasm resources for further study.

PMID- 24438238
TI  - Identification of intrinsic subtype-specific prognostic microRNAs in primary
      glioblastoma.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant type of glioma.
      Integrated classification based on mRNA expression microarrays and whole-genome
      methylation subdivides GBM into five subtypes: Classical, Mesenchymal, Neural,
      Proneural-CpG island methylator phenotype (G-CIMP) and Proneural-non G-CIMP.
      Biomarkers that can be used to predict prognosis in each subtype have not been
      systematically investigated. METHODS: In the present study, we used Cox
      regression and risk-score analysis to construct respective prognostic microRNA
      (miRNA) signatures in the five intrinsic subtypes of primary glioblastoma in The
      Cancer Genome Atlas (TCGA) dataset. RESULTS: Patients who had high-risk scores
      had poor overall survival compared with patients who had low-risk scores. The
      prognostic miRNA signature for the Mesenchymal subtype (four risky miRNAs: miR
      373, miR-296, miR-191, miR-602; one protective miRNA: miR-223) was further
      validated in an independent cohort containing 41 samples. CONCLUSION: We report
      novel diagnostic tools for deeper prognostic sub-stratification in GBM intrinsic
      subtypes based upon miRNA expression profiles and believe that such signature
      could lead to more individualized therapies to improve survival rates and provide
      a potential platform for future studies on gene treatment for GBM.

PMID- 24438241
TI  - Withdrawal Notice.
AB  - Zhi-Feng Xiang & Li-Xin Deng (2014): Complete mitochondrial genome of white
      Bengal tiger, Panthera tigris tigris, DOI: 10.3109/19401736.2013.873912. This
      article, published online ahead of print on 17 January 2014, has been withdrawn
      by the authors due to an error identified in the data. This updated withdrawal
      notice replaces the original withdrawal notice, which still included the
      published article in full.

PMID- 24438240
TI  - The complete mitochondrial genome sequence of Parabramis pekinensis strenosoma
      (Cypriniformes: Cyprinidae).
AB  - Parabramis pekinensis strenosoma belongs to the family Cyprinidae. In the present
      study, we obtain the complete mitochondrial genome of P. pekinensis strenosoma by
      PCR amplification and DNA sequencing. It is a circular double-stranded DNA
      molecule of 16,623 base pairs in length, consisting of the typical structure of
      22 transfer RNA genes, 13 protein-coding genes, 2 ribosomal RNA genes, as well as
      2 main non-coding regions (the control region and the origin of the light strand
      replication). Compared with Parabramis pekinensis, the two different subspecies
      share 99.58% nucleotide sequence similarity and the biggest nucleotide sequence
      discrepancy between homologous genes are observed in ND2 for protein-coding genes
      and in tRNA-Ala for tRNA-coding genes. The complete mitochondrial genome sequence
      data are of great use for phylogenetic analysis and studies of population
      genetics and germplasm resources of P. pekinensis strenosoma. 

PMID- 24438242
TI  - Complete mitochondrial genome of a cavefish, Sinocyclocheilus anophthalmus
      (Cypriniformes: Cyprinidae).
AB  - In this work, we report the complete mitochondrial genome sequence of a cavefish
      Sinocyclocheilus anophthalmus. The total length of the mitogenome was 16,574 bp
      and its overall base composition was estimated to be 31.1% for A, 25.5% for T,
      26.9% for C and 16.5% for G, indicating an A-T (56.6%)-rich feature in cavefish
      mitogenome. It contained the typical structure of 13 protein-coding genes, two
      ribosomal RNA genes, 22 transfer RNA genes and a non-coding control region (D
      loop region). The arrangement of these genes was the same as that found in other
      fishes. All the protein initiation codons were ATG, except for COX1 starting with
      GTG. The complete mitochondrial genome sequence of the cavefish would provide new
      insight for cavefish's genetic mechanisms.

PMID- 24438243
TI  - Characterization of the mitochondrial genome of the Shortfin scad Decapterus
      macrosoma (Perciformes: Carangidae).
AB  - The complete mitochondrial genome sequence of Decapterus macrosoma has been
      obtained with overlapped polymerase chain reaction. The genome was 16,545 bp in
      length which contained 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2
      non-coding regions (the control region and the light strand replication origin).
      Gene organization was similar to that observed in most other vertebrates. With
      the exception of the ND6 and eight tRNA genes, all other genes were encoded on
      the heavy strand. The genome was composed of 27.0% A, 30.4% C, 25.4% T and 17.2%
      G, showing an obvious anti-G bias commonly observed in teleosts. Two termination
      associated sequence regions (TAS-1 and TAS-2), three central conserved sequence
      blocks (CSB-F, CSB-E and CSB-D), and three conserved sequence blocks (CSB-1, CSB
      2 and CSB-3) were identified within the control region. The sequence data of D.
      macrosoma could provide useful information for the studies on molecular
      systematics and population genetics.

PMID- 24438244
TI  - Withdrawal notice.
AB  - Zhi-Feng Xiang & Li-Xin Deng (2014): Whole mitochondrial genome of the white
      African lion, Mitochondrial DNA, DOI: 10.3109/19401736.2013.873911. This article,
      published online ahead of print on 17 January 2014, has been withdrawn by the
      authors due to an error identified in the data. This updated withdrawal notice
      replaces the original withdrawal notice, which still included the published
      article in full.

PMID- 24438245
TI  - The complete mitochondrial genome sequence of the Tibetan wolf (Canis lupus
      laniger).
AB  - In this study, the complete mitochondrial genome of the Tibetan wolf (Canis lupus
      laniger) was sequenced using blood samples obtained from a wild female Tibetan
      wolf captured from Lhasa in Tibet, China. Qinghai-Tibet Plateau, with an average
      elevation above 3500 m, is the highest plateau in the world. Sequence analysis
      showed that its structure is in accordance with other Canidae species, but GTG is
      used as the start codon in ND4L gene which is different from many canide animals.

PMID- 24438246
TI  - The complete mitochondrial genome of the pygmy squid, Idiosepius (Cephalopoda:
      Decapodiformes): the first representative from the family Idiosepiidae.
AB  - We report the first complete mitochondrial genome of the pygmy squid, Idiosepius,
      (Idiosepiidae). The mtDNA genome is 16,183 bp long with an AT content of 75.4%.
      All conserved metazoan mitochondrial genes are identified with the addition of a
      1018 bp non-coding region. Idiosepius gene order most closely resembles that of
      the bobtail squid Semirossia (Sepiolidae).

PMID- 24438247
TI  - Complete mitochondrial genome of the urohaze-goby Glossogobius olivaceus
      (Perciformes, Gobiidae) and structure comparison of light strand replication
      origin in Gobioidei.
AB  - The genome of Glossogobius olivaceus (G. olivaceus) was 16,568 bp in length with
      a standard set of 13 protein-coding genes, 22 transfer RNA genes (tRNAs), 2
      ribosomal RNA genes (rRNAs) and 2 non-coding region (the control region and
      origin of the light strand replication). The conserved motif 5'-GCCGG-3' was
      determined in the origin of light strand replication of G. olivaceus. The G.
      olivaceus mitogenome base composition was: T 25.65%, C 29.82% A 27.17% and G
      17.36%, with a slight A+T bias of 52.82%, which was similar to most of the
      vertebrate mitogenomes. The mitochondrial genome of G. olivaceus had common
      features regarding gene arrangement and tRNA structures compared with those of
      other bony fishes.

PMID- 24438248
TI  - Complete mitochondrial genome of the mangrove whipray Himantura granulata
      (Myliobatiformes: Dasyatidae).
AB  - In this study, the complete mitogenome of mangrove whipray Himantura granulata
      was first determined. It is 17,657 bp in length and consists 22 tRNA genes, 2
      rRNA genes, 13 protein-coding genes and 1 putative control region with the
      typical gene arrangement and transcriptional orientation in vertebrates. Two
      start codon patterns and two stop codon patterns were found in the protein-coding
      genes. The tRNA-Ser2 (GCU) could not form the typical clover-leafs structure for
      lacking the dihydrouridine arm. The control region is 1914 bp in length with poor
      G (14.9%) and high A + T (59.1%) content.

PMID- 24438249
TI  - The complete sequence of the mitochondrial genome of Duroc pig (Sus Scrofa).
AB  - In this study, the total length of mitochondrial genome of Duroc pig is 16,731
      bp, including 34.66% A, 26.27% C, 25.74% T and 13.33% G. Mitochondrial genome
      contains a major non-coding control region (D-Loop region), 2 ribosomal RNA
      genes, 13 protein-coding genes (PCGs) and 22 transfer RNA genes. ND2 selects ATT
      as the initiation codon, and ATA is chose as an initiation codon in ND3 and ND5,
      the nonstandard start codon is GTG in ND4L and the rest protein common start
      codon is ATG. The mitochondrial genome of Duroc pig provides an important data in
      genetic mechanism, which plays an important role in the three-way crossbred pigs.

PMID- 24438250
TI  - PCR-RFLP identification of four Chinese soft-shelled turtle Pelodiscus sinensis
      strains using mitochondrial genes.
AB  - A PCR-RFLP method to confirm the identification of four Pelodiscus sinensis
      strains (Taihu Lake strain, Taiwan strain, Yellow River strain and Japanese
      strain) was developed and evaluated. In this study, we sequenced and analyzed the
      partial sequences of mitochondrial NADH4, COX I and NADH5-NADH6 genes of 60
      individuals from the four P. sinensis strains. Bgl I, Hpa II and Cla I were
      selected for cutting NADH4, COX I and NADH5-NADH6 PCR products, respectively, and
      each strain has its unique restriction band patterns. The result showed that all
      the 140 samples tested can be correctly identified based on the combination of
      the three digested fragments pattern. This study provides an effective method to
      distinguish the four main strains of P. sinensis. 

PMID- 24438251
TI  - The complete mitochondrial genome of Paraplagusia blochii (Pleuronectiformes:
      Cynoglossidae).
AB  - Paraplagusia blochii (Cynoglossidae, Soleoidei) is characterized by both eyes on
      the left side of the body with a short rostral hook reaching only to hind margin
      of lower eye. Here we first report the mitogenome of this tongue sole, which is
      16,611 bp in length, and the gene order has been reorganized. Specifically, the
      tRNA-Gln gene encoded by the light strand (L-strand) has been translocated to the
      heavy strand (H-strand), accompanied by the tRNA-Ile gene shuffling. In addition,
      the putative control region has been translocated downstream to a position
      between the ND1 and tRNA-Gln genes, leaving a 24-bp trace fragment in the
      original position. Nevertheless, the rest gene arrangement is identical to that
      of the typical fish. The determination of the complete mitogenome sequence of P.
      blochii could contribute to a better understanding the molecular mechanisms of
      gene reorganization in fish mitogenome and phylogenetic study of Soleidae and
      Pleuronectiformes.

PMID- 24438252
TI  - Complete mitochondrial genome of Tundra swan Cygnus columbianus jankowskii
      (Anseriformes: Anatidae).
AB  - Cygnus columbianus jankowskii is a subspecies of Tundra swan, which breeds in
      eastern Russia and northeast China, wintering in the middle and lower reaches of
      the Yangtze River. In this study, we used PCR-based method to obtain the complete
      mtDNA of this subspecies. The arrangement pattern of the complete mtDNA is
      identical with typical bird species, which is the shortest (16,723 bp) in three
      subspecies. The length of the PCGs is same except ND2, ND3 and ND6, and the
      initiation/termination codons are all same with other subspecies. The length of
      12S rRNA and 16S rRNA is same with C. c. columbianus, but different from C. c.
      bewickii. The length and structure of all tRNAs are the same with other
      subspecies except for tRNA(Ile), tRNA(leu(CUN)) and tRNA(ser(AGY)). The control
      region is located between tRNA(Phe) and tRNA(Glu), but the length is different
      with others.

PMID- 24438253
TI  - The complete mitochondrial genome of the Chinese indigenous dog.
AB  - In this study, the complete nucleotide sequence of Chinese indigenous dog
      mitochondrial genome was determined for the first time. Sequence analysis showed
      that the genome structure was in accordance with other dogs. It contained 22 tRNA
      genes, 2 ribosomal RNA genes, 13 protein-coding genes and 1 control region (D
      loop region). The base composition was A (31.6%), G (14.2%), C (25.5%) and T
      (28.7%), so the percentage of A and T (60.3%) was higher than that of G and C.
      The complete mitochondrial genome sequence of the Chinese indigenous dog would
      shed a new light on further studies in dog domestication. 

PMID- 24438254
TI  - Complete mitochondrial genome of the mudskipper Boleophthalmus boddarti
      (Perciformes, Gobiidae).
AB  - The Boddart's goggle-eyed mudskipper, Boleophthalmus boddarti (Perciformes,
      Gobiidae) is an amphibious fish, inhabiting brackish waters of estuaries and
      builds burrows in soft mud along the intertidal zone. In this paper, the complete
      mitochondrial genome sequence of B. boddarti was firstly determined. The circle
      genome (16,727 bp) comprises 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes
      and 1 control region. The overall base composition of B. boddarti is 29.1% for C,
      28.9% for A, 25.9% for T, and 16.0% for G, with a slight A + T bias of 54.8%. The
      termination-associated sequence, conserved sequence block domains, and a 131-bp
      tandem repeat were found in the control region. It has the typical vertebrate
      mitochondrial gene arrangement.

PMID- 24438255
TI  - The complete mitochondrial genome of the oblong rockfish Sebastes oblongus
      (Scorpaenidae, Scorpaeniformes).
AB  - The complete mitogenome of the oblong rockfish Sebastes oblongus was constructed
      using next-generation sequencing. The full genome was 16,396 bp in length,
      including two rRNA, 22 tRNA, one control region and 13 protein-coding genes
      (PCGs). The genome consisted of 28.0% A, 26.4% T, 16.9% G and 28.6% C, showing a
      slight AT bias (54.4%). All PCGs contained an ATG start codon, excluding COX1
      that contained a GTG. All PCGs contained the stop codon TAA, excluding ND3 (TAG
      stop codon) and Cytb (incomplete termination codon, T). All tRNAs contained the
      typical clover leaf structure, except for two tRNAs, serine (AGY) and threonine,
      which lacked the DHU arm. The complete mitogenome of S. oblongus will contribute
      to genetic analysis of the effective population size for aquaculture.

PMID- 24438256
TI  - Complete mitochondrial genome of the needle cuttlefish Sepia aculeata (Sepioidea,
      Sepiidae).
AB  - In this study, we determined the complete mitochondrial genome of the needle
      cuttlefish Sepia aculeata. The genome was 16,219 bp in length and contained 13
      protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 main non
      coding regions [both are control regions (CR)]. The composition and order of
      genes, for the mitogenome found in S. aculeate, were similar to most other
      invertebrates. The overall base composition of S. aculeata is T 34.0%, C 17.0%, A
      40.5% and G 8.5%, with a highly A + T bias of 74.5%. Two control regions (CR)
      both contain termination-associated sequences and conserved sequence blocks. This
      mitogenome sequence data would play an important role in the investigation of
      phylogenetic relationship, taxonomic resolution and phylogeography of the
      Sepiidae.

PMID- 24438257
TI  - The complete mitochondrial genome of Sebastes pachycephalus (Scorpaenidae,
      Scorpaeniformes) from the East Sea, Korea.
AB  - Due to variations in coloration as well as other morphological features, the
      identification of Sebastes pachycephalus has been problematic. The complete
      mitogenome of S. pachycephalus was acquired using next-generation sequencing. The
      full genome was 16,415 base pairs (bp) in length, assembling two rRNAs, 22 tRNAs,
      one control region and 13 protein-coding genes (PCGs). The genome constitutes
      27.9% A, 26.3% T, 17.2% G and 28.5% C, showing a slight AT bias (54.2%). All PCGs
      start with an ATG initial codon except COX1, which contains GTG. Most PCG stop
      codons were TAA, except for ND1 and ND3 (TAG) and Cytb (incomplete termination
      codon, T). All tRNAs showed the typical cloverleaf structure, except
      tRNA(Ser(AGY)), which lacks the DHU arm. The complete mitogenome of S.
      pachycephalus will help further identification and speciation analyses. 

PMID- 24438258
TI  - The complete mitochondrial genome of western painted turtle, Chrysemys picta
      bellii (Chrysemys, Emydidae).
AB  - In this study, we report the complete mitochondrial genome sequence of western
      painted turtle, Chrysemys picta bellii. The genome is found to be 16,875 bp in
      length and has a base composition of A (34.4%), G (13.0%), C (26.0%), and T
      (26.6%). Similar to other turtles, it contains a typically conserved structure
      including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes,
      and 1 control region (D-loop). Most of the genes are encoded on H-strand, except
      for the eight tRNA and ND6 genes. All protein-coding genes start with an ATN
      codon except for COX1 and ND4, which initiate with GTG instead, and terminate
      with the typical stop codon (TAA/TAG) or a single T (T-) or an unexpected codon
      of AGG. The complete mitochondrial genome sequence provided here would be useful
      for further phylogenetic analysis and conservation genetic studies in C. p.
      bellii.

PMID- 24438259
TI  - The complete mitochondrial genome of Paracymoriza distinctalis (Lepidoptera:
      Crambidae).
AB  - The complete mitochondrial genome of Paracymoriza distinctalis (Leech, 1889) has
      been determined in this article. The mitochondrial genome of P. distinctalis was
      15,354 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA
      (tRNA) genes, 2 ribosomal RNA (rRNA) genes and an A + T-rich region. All PCGs
      start with ATN codon, except for COI, which begins with CGA. Eleven PCGs stop
      with typical stop codon TAA. But ND5 and COII use incomplete stop codon T. All
      the 22 tRNAs have the typical clover-leaf structure except for tRNA(Ser)(AGN)
      lacking the dihydrouridine (DHU) stem. There were several conserved motifs in the
      intergenic region between tRNA(Ser)(UCN) and ND1 and the A + T-rich region of P.
      distinctalis.

PMID- 24438260
TI  - The complete mitochondrial genome of Odontesthes sp. (Atheriniforms,
      Atherinopsidae).
AB  - In this study, the complete mitochondrial genome of Odontesthes sp. has been
      studied first. The genome is 16,528 bp in length and contains 13 protein-coding
      genes, 22 tRNA genes, 2 ribosomal RNA genes and 1 putative control region. The
      mitochondrial genome of Odontesthes sp. had common features about gene
      arrangement and tRNA structures compared with those of other teleost fishes. The
      overall base composition of Odontesthes sp. is T 27.3%, C 29.4%, A 26.0% and G
      17.3%, with a slight A+T bias of 53.3%. Meanwhile, the conserved motif 5'-GCCGG
      3' was determined in the origin of light-strand replication of Odontesthes sp.
      The mitochondrial genome of this species would play an important role in the
      phylogenetics of Atherinopsidae.

PMID- 24438261
TI  - The complete mitochondrial genome of the tarnished plant bug, Lygus lineolaris
      (Heteroptera: Miridae).
AB  - The complete mitochondrial genome of the tarnished plant bug, Lygus lineolaris,
      comprised 17,027 bp. The genome contained 13 protein coding regions, 22 tRNA
      genes and 2 ribosomal RNA genes. The gene arrangement corresponded to the common
      order found among insect mtDNAs which was considered to be the ancestral
      arrangement. The protein coding genes started with ATN and stopped with TAA or
      TAG. The nucleotide distribution was 76.0% A + T. The control region contained
      two repeat regions, one was 24 bp and the other was 161 bp. The Genbank accession
      for the complete L. lineolaris mt genome is EU401991.

PMID- 24438262
TI  - The complete mitochondrial genome of the Xuefeng black-boned chicken.
AB  - Xuefeng black-boned chicken is one of the famous native breeds in China. In this
      work, we reported the complete mitochondrial genome sequence of the Xuefeng black
      boned chicken for the first time, which was determined through PCR-based method.
      The total length of the mitogenome was 16,783 bp, with the base composition of
      30.24% for A, 23.72% for T, 32.52% for C, 13.53% for G, in the order C > A > T >
      G feature occurring in the Xuefeng black-boned chicken. It contained the typical
      structure, including 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer
      RNA genes and 1 non-coding control region (D-loop region). It was similar to the
      gene arrangement in Silky chicken. The complete mitochondrial genome sequence of
      the Xuefeng black-boned chicken provided an important data for further study on
      the genetic mechanism.

PMID- 24438263
TI  - Mitochondrial genome of the Anas crecca (Anatidae: Anas).
AB  - Mitochondrial DNA plays an important role in living organisms, and has been used
      as a powerful molecular marker in various evolutionary studies. In this study, we
      determined the complete mitochondrial genome of Anas crecca (16,601 bp in
      length). Similar to the typical mtDNA of vertebrates, it contained 37 genes (13
      protein-coding genes, 2 rRNA genes and 22 tRNA genes) and a non-coding region (D
      loop). Overall base composition of the complete mitochondrial DNA was 29.05% A,
      22.35% T, 32.64% C and 15.96% G.

PMID- 24438264
TI  - The complete mitochondrial genome sequence of Microphysogobio tafangensis
      (Cypriniformes: Cyprinidae).
AB  - In the present study, the total mitochondrial genome of Microphysogobio
      tafangensis (Cypriniformes: Cyprinidae) was determined. The full genome was
      16,683 bp in length, which consisted of 13 protein-coding genes, 22 tRNA genes, 2
      rRNA genes and 2 non-coding regions. The nucleotide composition of M. tafangensis
      mitochondrial genome was A: 29.38%, G: 17.71%, T: 25. 47% and C: 27.44%.

PMID- 24438265
TI  - Complete mitochondrial genome of Zebra tilapia, Tilapia buttikoferi.
AB  - We determined the complete mitochondrial genome of Tilapia buttikoferi, which was
      16,577 bp in length with an A + T content of 53.0%, containing 13 protein-coding
      genes, 2 rRNAs, 22 tRNAs and a complete control region. The gene arrangement was
      similar to that of typical fishes. The total base composition of the mitogenome
      was 25.6% T, 30.8% C, 27.4% A and 16.2% G. Of the 13 protein-coding genes, 12
      genes start with an ATG codon, except for COX1 with GTG. Seven (ND1, ND2, COX1,
      ATPase8, ATPase6, ND4L and ND6) used TAA or AGA as the termination codon, whereas
      six (COX2, COX3, ND3, ND4, ND5 and cyt b) had incomplete stop codon T. Its
      control region was atypical in being short at 861 bp, and contained TACAT motif
      and one microsatellite-like region (TA)7. This mitogenome sequence data may be
      useful for phylogenetic and systematic analyses within the family Cichlaidae.

PMID- 24438266
TI  - The complete mitochondrial genome of Peripolus nepalensis Uvarov, 1942
      (Orthoptera: Acridoidea: Catantopidae).
AB  - The complete mitochondrial genome of Peripolus nepalensis, which was collected
      from the Tibetan Plateau, is reported here. It is 15,858 bp in length and
      contains 74.3% AT. All P. nepalensis protein-coding sequences start with a
      typical ATN codon. The usual termination codons (TAA or TAG) and incomplete stop
      codons (T or TA) were found from 13 protein-coding genes. All tRNA genes could be
      folded into the typical clover-leaf secondary structure, excluding trnS(AGN)
      which forms another structure. The sizes of the large and small ribosomal RNA
      genes were 1324 and 862 bp, respectively. The AT content of the A + T-rich region
      was 83.8%.

PMID- 24438267
TI  - Complete sequence and rearrangement of the mitochondrial genome of Garra
      qiaojiensis (Cypriniformes: Cyprinidae).
AB  - The complete mitochondrial sequence of Garra qiaojiensis was obtained by PCR. It
      was 17,096 bp in length and comprised 22 transfer RNA genes, 13 protein-coding
      genes, 2 ribosomal RNA genes and 3 non-coding regions. Unlike the typical
      mitochondrial genome organization in vertebrate, the mitochondrial genome of G.
      qiaojiensis was characterized by the distinctive feature: translocation of the
      tRNA-Pro gene followed by a 258-bp tandem repeat non-coding region. The
      dinucleotide microsatellite (TA)n which is rather constant in the control region
      in Cypriniformes was scattered into the tandem repeat non-coding region in the G.
      qiaojiensis mitochondrial genome with the number of repeated units reduced.

PMID- 24438268
TI  - Complete mitochondrial genome of a brown frog, Rana kunyuensis (Anura: Ranidae).
AB  - The first complete mitochondrial genome (mitogenome) of Rana sensu stricto (sensu
      Frost, 2013) was determined using Rana kunyuensis as a representative species.
      The mitogenome was 22,255 bp in length, including 13 protein-coding genes, 22
      transfer RNA genes, 2 ribosomal RNA genes and duplicated control regions. The
      mitogenome of R. kunyuensis showed novel gene order arrangement with a
      translocation of tRNA(Leu)((CUN)) and ND5 in comparison with published anuran
      mitogenomes to date. This mitogenome should contribute to understand the
      evolution of anuran mitochondrial gene order arrangements.

PMID- 24438269
TI  - The complete mitochondrial genome of the Chinese rhesus macaques, Macaca mulatta
      lasiota.
AB  - In this study, the complete mitochondrial genome sequence of the Chinese rhesus
      macaques Macaca mulatta lasiota has been reported for the first time. The total
      length of the mitogenome was 16,561 bp. It contained the typical structure,
      including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes
      and 1 control region. The overall composition of the mitogenome was A (31.7%), G
      (12.8%), C (30.4%) and T (25.1%). The M. mulatta lasiota mitogenome had 21 tRNA
      genes folded into a typical clover-leaf secondary structure except for tRNA(Ser).

PMID- 24438270
TI  - Complete mitochondrial genomes of domesticated and wild common carp (Cyprinus
      carpio L.).
AB  - Glass red common carp (Cyprinus carpio var. wananensis) were occasionally found
      among wild common carp (Cyprinus carpio) 50 years ago. In this paper, we
      determined the complete sequences of Glass red common carp and wild common carp
      mitogenomes. Both mitogenomes exhibited the same length of 16,581 bp, order in 13
      protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 control region. The
      sequence similarity between them reached 99.62% and 100% in 21 tRNA genes
      (excluding tRNA(Ser)) and 2 protein-coding genes (ATP8 and ND4L), respectively.
      The two mitogenomes will be useful in elucidating the evolutional relationship of
      the common carp.

PMID- 24438271
TI  - Mitochondrial genome of the black flying fox, Pteropus alecto (Chiroptera:
      Megachiroptera: Pteropodidae).
AB  - In this article we report the complete mitochondrial genome of black flying fox,
      Pteropus alecto, with the sequence length of 16,739 bp for the first time. The
      mitogenome contained a total of 13 protein-coding genes, 22 transfer RNA genes, 2
      ribosomal RNA genes and 1 control region. The base composition was A (33.1%), G
      (14.5%), C (27.2%) and T (25.2%), indicating that the percentage of A and T
      (58.3%) was higher than that of G and C. Most of these genes were distributed on
      the H-strand, except for the ND6 subunit gene and eight tRNA genes. The
      mitochondrial genome analyzed here will provide new genetic information to study
      the evolution of bats. 

PMID- 24438272
TI  - Complete mitochondrial genome of the marine polychaete, Marphysa sanguinea
      (Polychaeta, Eunicida).
AB  - The complete mitochondrial genome of Marphysa sanguinea from northern China was
      determined. This entire sequence was 15,159 bp in length, containing 13 protein
      coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and a putative control region (D
      loop). The base composition of the genome was 30.7% A, 30.3% T, 26.5% C and 12.6%
      G. Some PCGs shared nucleotides with neighboring genes, and all 13 PCGs had ATG
      as a start codon. Two complete stop codons (TAA, TAG) were used by the PCGs.
      Compared to other marine polychaetes and oligophaetes, most of the PCGS were
      without any rearrangement, except for ND2 and ND3, in which the order was
      reversed.

PMID- 24438273
TI  - The complete mitochondrial genome of Microhyla pulchra (Amphidia, Anura,
      Microhylidae).
AB  - The complete mitochondrial genome of Microhyl pulchra was determined in this
      work. This mitogenome was 16,744 bp in length, containing 13 protein-coding
      genes, 2 rRNA genes, 22 tRNA genes and a control region (CR). The following four
      distinctive features were observed: a protein-coding gene (ND1) began with GTG as
      start codon; eight protein-coding genes (ND1, COII, ATP6, COIII, ND3, ND4, ND5
      and Cytb) ended with incomplete stop codon T; four tRNA genes positions (tRNA-Leu
      (CUN)/tRNA-Thr/Trna-Pro/tRNA-Phe) located between CR and 12S rRNA genes, which
      was a novel mtDNA gene rearrangement in amphibians; there was no significant
      repeat regions in the CR.

PMID- 24438274
TI  - The complete mitochondrial genome of Squalidus argentatus (Cypriniformes,
      Cyprinidae).
AB  - In the present study, the complete mitogenome sequence of the Cyprinid fish
      Squalidus argentatus (Cypriniformes, Cyprinidae) was determined. The mitogenome,
      consisting of 16,609 base pairs (bp), was characterized by the typical vertebrate
      mitochondrial gene arrangement, including 13 protein-coding, 22 transfer RNAs, 2
      ribosomal RNAs genes and a noncoding control region. Control region (CR), of 931
      bp in length, was located between tRNA(Pro) and tRNA(Phe). The overall base
      composition of S. argentatus was 30.45% for A, 16.70% for G, 25.62% for T and
      27.24% for C, with a slight AT bias of 56.07%.

PMID- 24438275
TI  - Complete mitochondrial genome of a satyrid butterfly, Ninguta schrenkii
      (Lepidoptera: Nymphalidae).
AB  - The complete mitochondrial genome of N. schrenkii is 15,261 bp in length,
      containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2
      ribosomal RNA genes (LrRNA and SrRNA) and 1 non-coding A + T-rich region. The
      nucleotide composition is significantly biased toward A + T (80.2%), similar to
      the known satyrid species. All PCGs utilize the typical mitochondrial start codon
      ATN, except for COI, which is initiated with CGA. Seven PCGs use complete stop
      codon (TAA), whereas ND1 and ND4 use TA as stop codon and COI, COII and ND5 end
      with single T. The A + T-rich region of N. schrenkii is 403 bp in length, which
      contains several features common to the other lepidopteran species.

PMID- 24438276
TI  - The mitochondrial genome of the gold-dust day gecko, Phelsuma laticauda (Sauria,
      Gekkota, Gekkonidae).
AB  - We sequenced the nearly complete mitochondrial genome of the gold-dust day gecko,
      Phelsuma laticauda, which is native to northern Madagascar. The mitogenome is
      15,416 bp in size, consisting of 37 genes coding for 13 proteins, 22 tRNAs, and 2
      rRNAs. Due to the unsuccessful sequencing of the control region, the length is
      relatively shorter than that of other gekkonids. The gene organization conforms
      to the vertebrate consesus gene arrangement.

PMID- 24438277
TI  - The complete mitochondrial genome of the juvenile Pacific bluefin tuna Thunnus
      orientalis (Perciformes, Scombridae).
AB  - The complete mitochondrial genome of the juvenile Pacific bluefin tuna Thunnus
      orientalis collected from Sea of Japan was determined by next-generation
      sequencing. The mitogenome is a circular molecule 16,529 bp in length, including
      the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA genes and a control region. The termination-associated sequence
      (TAS), central conserved sequence blocks (CSB) and CSB were detected in the
      control region. The gene contents of the mitogenome are identical to those
      observed in most bony fishes.

PMID- 24438278
TI  - Mitochondrial genome of the spotless smooth-hound Mustelus griseus
      (Carcharhiniformes: Triakidae).
AB  - The complete mitochondrial genome of Mustelus griseus was first determined in
      this study. It is 16,754 bp in length, consisting of 13 protein-coding genes, 2
      rRNA genes, 22 tRNA genes and 1 control region with the typical gene order in
      vertebrates. Overall nucleotide base composition of the mitogenome is 30.7% A,
      24.9% C, 14.0% G and 30.3% T. After aligning, it comes to us that the mitogenomic
      portions of M. griseus are very similar to those of Mustelus manazo, ranging from
      86.92% (control region) to 100% (tRNA-His and tRNA-Leu2). The origin of L-strand
      replication (OL) is identified between tRNA-Asn and tRNA-Cys genes. The control
      region is located between the tRNA-Pro and tRNA-Phe genes, containing one
      termination-associated sequence (TAS) and three short conserved sequences (CSB 1
      3).

PMID- 24438279
TI  - The complete mitochondrial genome of Orinhippus tibetanus Uvarov, 1921
      (Orthoptera: Acridoidea: Gomphoceridae).
AB  - The complete mitochondrial genome of Orinhippus tibetanus, which was collected
      from the Tibetan Plateau, is reported here. It is 15,611 bp in length and
      contains 74.2% AT. All O. tibetanus protein-coding sequences except for the cox1
      start with a typical ATN codon. The usual termination codons (TAA or TAG) and
      incomplete stop codons (T or TA) are found from 13 protein-coding genes. All tRNA
      genes could be folded into the typical cloverleaf secondary structure, except
      trnS(AGN) lacking of dihydrouridine (D) arm. The sizes of the large and small
      ribosomal RNA genes are 1317 and 854 bp, respectively. The AT content of the A +
      T-rich region is 84.8%.

PMID- 24438280
TI  - The complete mitochondrial genome of Java warty pig (Sus verrucosus).
AB  - In the present study, the complete mitochondrial genome sequence of the Java
      warty pig was reported for the first time. The total length of the mitogenome was
      16,479 bp. It contained the typical structure, including 2 ribosomal RNA genes,
      13 protein-coding genes, 22 transfer RNA genes and 1 non-coding control region (D
      loop region) as that of most other pigs. The overall composition of the
      mitogenome was estimated to be 34.9% for A, 26.1% for T, 26.0% for C and 13.0%
      for G showing an A-T (61.0%)-rich feature. The mitochondrial genome analyzed here
      will provide new genetic resource to uncover pigs' evolution. 

PMID- 24438281
TI  - The complete mitogenome of the freshwater crayfish Cherax cainii (Crustacea:
      Decapoda: Parastacidae).
AB  - The complete mitochondrial genome of Cherax cainii was recovered from partial
      genome sequencing data using the HiSeq platform. The mitogenome consists of
      15,801 base pairs (69% A + T content) containing 13 protein-coding genes, 2
      ribosomal subunit genes, 22 transfer RNAs and a 783 bp non-coding AT-rich region.
      This is the second completely sequenced mitogenome from the genus Cherax after
      the first reported Cherax destructor mitogenome nearly a decade ago.

PMID- 24438282
TI  - The complete mitochondrial genome of Bos taurus coreanae (Korean native cattle).
AB  - Korean native cattle is one of the famous native breeds in Korean. In the present
      work, we report the complete mitochondrial genome sequence of Korean native
      cattle for the first time. The total length of the mitogenome was 16,339 bp with
      the base composition of 33.4% for A, 27.2% for T, 26.0% for C, and 13.4% for G,
      and an A-T (60.6%)-rich feature was detected. It harbored 13 protein-coding
      genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control
      region (D-loop region). The arrangement of all genes was identical to the typical
      mitochondrial genomes of cattle. The complete mitochondrial genome sequence of
      Korean native cattle would serve as an important data set of the germplasm
      resources for further study.

PMID- 24438283
TI  - Complete mitochondrial genome of a German Shepherd (Canis lupus familiaris breed
      German Shepherd) provides insights into genome-wide sequence variations.
AB  - In this work, we report the complete mitochondrial genome sequence of a German
      shepherd. The total length of the mitogenome was 16,727 bp. It contained the
      typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer
      RNA genes and a non-coding control region (D-loop region). The arrangement of
      these genes was the same as that found in other dogs. All the protein initial
      codons were ATG, except for ND2, ND3 and ND5 starting with ATA. Sequence
      comparison indicates that D-loop region harbors most sequence variations.

PMID- 24438284
TI  - Complete mitochondrial genome sequence of tarim red deer (Cervus elaphus
      yarkandensis).
AB  - The complete mitochondrial genome of the tarim red deer, Cervus elaphus
      yarkandensis, was determined by accurate polymerase chain reaction. The entire
      genome was 16,351 bp in length and contained 13 protein-coding genes, 2 rRNA
      genes, 22 tRNA genes and 1 control region, all of which were arranged in a
      typical vertebrate manner. The overall base composition of the northeast sika
      deer's mitochondrial genome was 33.3% of A, 24.4% of C, 28.9% of T and 13.4% of
      G. A termination-associated sequence and several conserved central sequence block
      domains were discovered within the control region.

PMID- 24438285
TI  - Mitochondrial genome sequence of Egyptian swift Rock Pigeon (Columba livia breed
      Egyptian swift).
AB  - The Egyptian swift Rock Pigeon is a breed of fancy pigeon developed over many
      years of selective breeding. In this work, we report the complete mitochondrial
      genome sequence of Egyptian swift Rock Pigeon. The total length of the mitogenome
      was 17,239 bp and its overall base composition was estimated to be 30.2% for A,
      24.0% for T, 31.9% for C and 13.9% for G, indicating an A-T (54.2%)-rich feature
      in the mitogenome. It contained the typical structure of 13 protein-coding genes,
      2 ribosomal RNA genes, 22 transfer RNA genes and a non-coding control region (D
      loop region). The complete mitochondrial genome sequence of Egyptian swift Rock
      Pigeon would serve as an important data set of the germplasm resources for
      further study. 

PMID- 24438286
TI  - Multiple introductions of the eastern fox squirrel (Sciurus niger) in California.
AB  - Eastern fox squirrels (Sciurus niger) have been introduced into California within
      the past 130 years. Recently, their range has been expanding at an alarming rate.
      Genetic diversity was assessed in 101 control region sequences of eastern fox
      squirrels from three geographic regions within California (Los Angeles County,
      Alameda and Contra Costa counties and Sacramento County) to determine if a single
      or multiple introductions occurred within California, as indicated by the
      detection of multiple haplotypes. A total of 11 haplotypes were discovered, with
      haplotypes rarely shared among geographic regions and no clustering by region in
      a haplotype network. This suggests that the introduction to different regions
      within California came from different source populations within the native range
      of the species. Haplotype diversity was highest in Los Angeles County. Due to a
      lack of phylogeographic structure in fox squirrels in their native range, it is
      difficult to identify the sources of all introductions. 

PMID- 24438287
TI  - The complete mitochondrial genome of the Babylonia lutosa.
AB  - The complete mitochondrial genome sequence of the Babylonia lutosa was determined
      using the PCR-based method. The total length of the mitogenome is 15,346 bp,
      including 2 ribosomal RNA genes, 13 protein-coding genes and 22 transfer RNA
      genes. The overall composition of the mitogenome was estimated to be 29.10% for
      A, 37.24% for T, 16.82% for C and 16.85% for G, indicating that an A + T (66.34%)
      rich feature occurs in the B. lutosa mitogenome.

PMID- 24438288
TI  - Retrospective assessment of the most common mitochondrial DNA mutations in a
      large Hungarian cohort of suspect mitochondrial cases.
AB  - Prevalence estimations for mitochondrial disorders still vary widely and only few
      epidemiologic studies have been carried out so far. With the present work we aim
      to give a comprehensive overview about frequencies of the most common
      mitochondrial mutations in Hungarian patients. A total of 1328 patients were
      tested between 1999 and 2012. Among them, 882 were screened for the m.3243A > G,
      m.8344A > G, m.8993T > C/G mutations and deletions, 446 for LHON primary
      mutations. The mutation frequency in our cohort was 2.61% for the m.3243A > G,
      1.47% for the m.8344A > G, 17.94% for Leber's Hereditary Optic Neuropathy
      (m.3460G > A, m.11778G > A, m.14484T > C) and 0.45% for the m.8993T > C/G
      substitutions. Single mtDNA deletions were detected in 14.97%, while multiple
      deletions in 6.01% of the cases. The mutation frequency in Hungarian patients
      suggestive of mitochondrial disease was similar to other Caucasian populations.
      Further retrospective studies of different populations are needed in order to
      accurately assess the importance of mitochondrial diseases and manage these
      patients.

PMID- 24438289
TI  - Complete mitochondrial genome of the flat bug Brachyrhynchus hsiaoi (Hemiptera:
      Aradidae).
AB  - The mitochondrial genome of a flat bug, Brachyrhynchus hsiaoi (Blote), is a
      typical circular DNA molecule of 15,250 bp with 37 genes and 70.4% A + T content.
      The gene order is different from that of the putative ancestral arrangement of
      insects with a tRNA gene rearrangement, trnQ-trnI. This rearrangement has been
      found in other sequenced flat bugs and is likely synapomorphic for the Aradidae
      or some subgroup within this family. Ten protein-coding genes start with ATN
      codon and others use TTG. All the 22 tRNAs, ranging from 61 to 70 bp, have the
      clover-leaf structure except for the dihydrouridine (DHU) arm of trnS1 forms a
      simple loop. The sizes of the large and small ribosomal RNA genes are 1245 and
      808 bp, respectively. The control region is located between rrnS and trnQ with
      703 bp in length and 69.8% A + T content.

PMID- 24438290
TI  - The complete mitochondrial genome of the Elaphe perlacea (Squamata: Colubridae).
AB  - The Pearl-banded rat-snake Elaphe perlacea (recently renamed Euprepiophis
      perlacea) belongs to the family Colubridae, and is only distributed in western
      Sichuan Province, China. In this study, the whole mitochondrial genome of E.
      perlacea was first sequenced. It was determined to be 17,160 bp and included 13
      protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 control regions (D-loop).
      Except for eight tRNAs and nd6 genes, all other mitochondrial genes were encoded
      on the heavy strand (H strand). Molecular data presented here provide a useful
      tool for helping set the stage for further studies and the molecular evolution of
      the mitochondrial genome.

PMID- 24438291
TI  - The complete mitochondrial genome of the juvenile Atlantic bluefin tuna Thunnus
      thynnus (Perciformes, Scombridae).
AB  - The complete mitochondrial genome of the juvenile Atlantic bluefin tuna Thunnus
      thynnus collected from Sea of Japan was determined by next-generation sequencing.
      The mitogenome is a circular molecule 16,529 bp in length, including the typical
      structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA
      genes and a control region. The TAS, central CSB and CSB were detected in the
      control region. The gene contents of the mitogenome are identical to those
      observed in most bony fishes.

PMID- 24438292
TI  - The complete mitochondrial genome of Bemisia afer (Hemiptera: Aleyrodidae).
AB  - The length of the Bemisia afer (Priesner & Hosny) (Hemiptera: Aleyrodidae)
      mitochondrial genome (mitogenome) is 14,968 bp and consists of 13 protein coding
      genes (PCGs), 21 transfer RNAs (tRNA), 2 ribosomal RNAs and 1 control region.
      Apart from one serine transfer RNA gene (tRNA-Ser) which is absent, the synteny
      is consistent with the mitogenomes of other whitefly species. The overall base
      composition of the heavy strand for A, G, T and C is 28.96, 18.97, 36.7 and
      15.37%, respectively, with a slight AT bias. Two rare codons (GTG and TTG) are
      employed as start codons by some PCGs. B. afer is a group of cryptic species.
      This first mitogenome cloned from African cassava B. afer, therefore, both enrich
      the whitefly molecular resource and will aid the sequencing of the other species'
      mitogenomes. It will contribute significantly to resolving the systematics of the
      B. afer complex.

PMID- 24438293
TI  - The complete mitochondrial genome sequence of Siniperca undulate (Perciformes:
      Percichthyidae).
AB  - In this paper, the complete mitochondrial DNA (mtDNA) sequence of Siniperca
      undulate was determined. The complete mtDNA genome sequence of S. undulate was
      16,504 bp in length. It consisted of 13 protein-coding genes, 22 transfer RNA
      genes, 2 rRNA genes and 2 non-coding regions. Overall base composition of
      mitogenome was estimated to be 28.38% for A, 29.43% for C, 16.46% for G and
      25.73% for T, respectively, with a high A + T content (54.11%). The complete
      mitogenome of the S. undulate can provide a basic data for the studies on
      population history, molecular systematics, phylogeography, stock evaluation and
      conservation genetics. It is also helpful to the reasonable utilization and
      development of rational management strategies for S. undulate resource.

PMID- 24438294
TI  - Organization and characterization of the mitochondrial genome of the Razorbelly
      scad Alepes kleinii (Perciformes: Carangidae).
AB  - The complete mitochondrial genome sequence of Alepes kleinii (Perciformes:
      Carangidae) was determined in this study. The entire sequence was 16,571 bp in
      length which contained 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and
      2 non-coding regions (the control region and the light strand replication
      origin). Gene organization and gene order were similar to that observed in most
      other vertebrates. Overall base compositions of the sequence were 28.0% of A,
      28.5% of C, 27.0% of T, and 16.5% of G, showing an obvious anti-G bias commonly
      observed in teleosts. Apart from the ND6 and eight tRNA genes, all other genes
      were encoded on the heavy strand. Three types of initiation codons were detected
      in the open reading frames of the protein-coding genes, including codon ATA which
      was rarely detected in Carangidae species. The complete mitogenome sequence data
      of A. kleinii could provide useful information for taxonomic and phylogenetics
      studies.

PMID- 24438295
TI  - The complete mitochondrial genome of an assassin bug Peirates arcuatus
      (Hemiptera: Reduviidae).
AB  - The complete mitochondrial genome of Peirates arcuatus (Stal) is a typical double
      stranded circular molecule 16,176 bp long with 37 genes usually present in animal
      mitochondrial genomes and a control region. Gene order is identical to that of
      the putative ancestral arrangement of insects and other assassin bugs. Thirteen
      protein-coding genes initiate with ATN codons and mostly terminate with TAN
      codons except for COII and COIII use a single T residue as the termination codon.
      All tRNA sequences can be folded into classic clover-leaf secondary structure
      except that the dihydrouridine (DHU) arm of tRNA(Ser(AGN)) forms a simple loop,
      and their length range from 63 to 69 bp. The control region is 1552 bp long and
      includes two complete 118-bp tandem repeats and one partial copy of anterior
      repeat unit.

PMID- 24438296
TI  - The complete mitochondrial genome of Papilio bianor (Lepidoptera: Papilionidae),
      and its phylogenetic position within Papilionidae.
AB  - The complete mitochondrial genome sequence of Papilio bianor was determined in
      the present paper. The complete mtDNA from P. bianor was 15,358 base pairs in
      length and contained 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes
      and a control region. The P. bianor genes were in the same order and orientation
      as the completely sequenced mitogenomes of other lepidopteran species. To
      determine the phylogentic position of P. bianor with related species within
      Papilionidae, the Bayesian phylogenetic tree was reconstructed with the
      concatenated nucleotide dataset of the 13 protein-coding genes. The phylogenetic
      trees confirmed that P. bianor and four species of Papilionidae clustered into a
      clade, and shared a close relationship with Papilio maraho. Meanwhile, the
      molecular phylogenetic trees also confirmed that Papilionidae is a monophyletic
      group, and Pieridae is closely related with Lycaenidae and Nymphalidae. 

PMID- 24438297
TI  - The complete mitochondrial genome of Leuciscus idus (Cypriniformes: Cyprinidae).
AB  - In this study, we determined the complete nucleotide sequence of the
      mitochondrial genome for a cold water fish, Leuciscus idus. The complete
      mitochondrial genome was sequenced and analyzed using the primer walking method
      and 30 pairs of newly designed primers were used. Direct sequencing of the PCR
      products demonstrated that the genome contained the same 37 mitochondrial genes
      (two ribosomal RNA, 22 transfer RNA and 13 protein-coding genes) and two main non
      coding regions (the control region and the origin of the light strand
      replication) as those found in other vertebrates. Nearly all the protein-coding
      genes' start codons were ATG except COX 1, meanwhile, the termination codons of
      which varied with TAA, TA, T, or TAG. 

PMID- 24438298
TI  - Identification of sequence nucleotide polymorphisms in the D-loop region of
      mitochondrial DNA as a risk factor for epithelial ovarian cancer.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) and mutations in the D-Loop
      region of mitochondrial DNA have been long proposed to drive the pathogenesis and
      progression of human malignancies. We investigated the links between SNPs of D
      Loop and epithelial ovarian cancer risk. METHOD: Mitochondrial DNA (mtDNA) of
      peripheral blood from 93 epithelial ovarian cancer patients and controls were
      examined for single nucleotide polymorphisms (SNPs) and mutations in the D-Loop
      region. RESULTS: The 73A/G, 207G/A and 523C/del (p < 0.05), which indicated that
      the patients who carry these alleles were susceptible to epithelial ovarian
      cancer. Additional SNPs 254T/G, 259A/G, 275G/A, 366G/A, 411C/G, 414T/G, 418C/G,
      441C/A, 476C/A, 524C/del, 530C/T were significantly associated with the tendency
      toward the increased risk for epithelial ovarian cancer. In contrast, the alleles
      249A/del and 263A/G were correlated with the reduced risk of epithelial ovarian
      cancer. CONCLUSION: In conclusion, SNPs in the mtDNA D-loop were found to be risk
      markers for epithelial ovarian cancer.

PMID- 24438299
TI  - The complete mitochondrial genome of the flesh fly, Boettcherisca peregrine
      (Diptera: Sarcophagidae).
AB  - The complete mitochondrial genome of Boettcherisca peregrine (B. peregrina), an
      important forensic entomology, was sequenced for the first time. The 14,922 bp
      circular genome contains 37 genes that were found in a typical Metazoan genome:
      13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. It also
      contains one non-coding A + T-rich region. The arrangement of the genes was the
      same as that found in the other insect. The overall base composition on heavy
      strand was as follows: A, 38.86%; G, 15.10%; C, 9.93%; T, 36.11%; and the A + T
      content 74.97%. The mitochondrial genome of Sarcophaga presented could be
      valuable for resolving phylogenetic relationships within the order Diptera and
      especially for the family Sarcophagidae. The molecular data presented may also be
      used to screen favorable molecular markers for species identifications for
      forensic entomology purposes.

PMID- 24438300
TI  - Complete mitochondrial genome of Thitarodes pui (Lepidoptera: Hepialidae).
AB  - To know the genetic structure and phylogeny status, the complete mitochondrial
      genome of Thitarodes pui was the first time to be sequenced. The genome was
      15,064 bp in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA
      genes, as well as an AT rich region. The base composition of the genome was A
      (40.93%), T (39.80%), C (11.72%) and G (7.55%), with an AT content of 80.73%. It
      is interesting to that the COI would start with CGA. The tRNA order between ND2
      and AT rich region was tRNA(Ile)-tRNA(Gln)-tRNA(Met), which confirms the thesis
      that Thitarodes has the ancestral gene arrangement. It is surprised that AT-rich
      region was 287 bp in length and became the shortest in contrast to other insects
      of Hepialidae.

PMID- 24438301
TI  - The complete mitochondrial genome of a purebred Tibetan Mastiff (Canis lupus
      familiaris breed Tibetan Mastiff) from Lijiang, China, and comparison of genome
      wide sequence variations.
AB  - In this study, the complete mitochondrial genome sequence of the Tibetan Mastiff
      was reported. The total length of the mitogenome is 16,729 bp. It contains the
      typical structure, including 13 protein-coding genes, 22 transfer RNA genes, 2
      ribosomal RNA genes and 1 control region is in line with other canine animals. We
      further identified genome-wide variations among different canine mitochondrial
      genomes and indicated that the D-loop region harbors the most sequence variation,
      which will provide sequence variation information for the protection and
      utilization of the Tibetan Mastiff germplasm resource.

PMID- 24438302
TI  - Mitochondrial genome sequence of the potato powdery scab pathogen Spongospora
      subterranea.
AB  - Spongospora subterranea is a soil-borne obligate parasite responsible for potato
      powdery scab disease. S. subterranea is a member of the order Plasmodiophorida, a
      protist taxa that is related to Cercozoa and Foraminifera but the fine details of
      these relationships remain unresolved. Currently there is only one available
      complete mtDNA sequence of a cercozoan, Bigelowiella natans. In this work, the
      mitochondrial sequence of a S. subterranea isolate infecting an Andean variety of
      S. tuberosum ssp. andigena (Diacol-Capiro) is presented. The mtDNA codes for 16
      proteins of the respiratory chain, 11 ribosomal proteins, 3 ribosomal RNAs, 24
      tRNAs, a RNA processing RNaseP, a RNA-directed polymerase, and two proteins of
      unknown function. This is the first report of a mtDNA genome sequence from a
      plasmodiophorid and will be useful in clarifying the phylogenetic relationship of
      this group to other members in the supergroup Rhizaria once more mtDNA sequences
      are available. 

PMID- 24438303
TI  - The complete mitochondrial genome of Cobitis granoei (Cyprinformes: Cobitidae).
AB  - Knowledge of animal mitochondrial genomes is very important to understand their
      molecular evolution and phylogenetic studies. Cobitis granoei (Rendahl, 1935)
      only had been sequenced D-loop gene and Cytb gene in past research. Here we
      determined the complete mitochondrial genome of C. granoei. The entire sequence
      was 16,636 bp in length, including 13 protein-coding genes (PCGs), 2 rRNA genes,
      22 tRNA genes and one control region (D-loop). All the PCGs used ATG as a start
      codon, except for COI gene, which with GTG as the start codon. Most of the PCGs,
      including ND1, COI, ATP8, ATP6, ND4L, ND5 and ND6 had TAA as termination codon.
      While the others were with the incomplete termination codons TA or T. The gene
      arrangement was in accordance with all known Cyprinformes mitochondrial genomes.

PMID- 24438304
TI  - Complete mitochondrial genome organization of Schizothorax plagiostomus (Heckel,
      1838).
AB  - The complete mitochondrial genome of Schizothorax plagiostomus, an endemic
      coldwater fish of Himalayas, was determined for the first time. The genome is
      16,576 bp in length and consists of 13 protein coding genes, 22 tRNAs, 2rRNA
      genes and 1 putative control region. The gene organization and its order were
      similar to other vertebrates. The overall base composition was A 30%, G 17.4%, C
      26.8%, T 25.8%, A + T content 55.8% and the G + C content 44.2%. The control
      region consists of a microsatellite locus (TA)12 between 16,460 and 16,483 bp.
      The present study will provide the rationale for the management and conservation
      of S. plagiostomus.

PMID- 24438305
TI  - Two molecular markers based on mitochondrial genomes for varieties identification
      of the northern snakehead (Channa argus) and blotched snakehead (Channa maculata)
      and their reciprocal hybrids.
AB  - The northern snakehead (Channa argus) and blotched snakehead (Channa maculata)
      and their reciprocal hybrids have played important roles in the Chinese
      freshwater aquaculture industry, with an annual production in China exceeding 400
      thousand tons. While these are popular aquaculture breeds in China, it is not
      easy to identify northern snakehead, blotched snakehead, and their hybrids. Thus,
      a method should be developed to identify these varieties. To distinguish between
      the reciprocal hybrids (C. argus ? * C. maculata ? and C. maculata ? * C. argus
      ?), the mitochondrial genome sequences of northern snakehead and blotched
      snakehead and their reciprocal hybrids were compared. Following the alignment and
      analysis of mtDNA sequences of northern snakehead, blotched snakehead and their
      hybrids, two pairs of specific primers were designed based on identified
      differences ranging from 12S rRNA to 16S rRNA gene. The BY1 primers amplified the
      same bands in the blotched snakehead and the hybrid (C. maculata ? * C. argus ?),
      while producing no products in northern snakehead and the hybrid (C. argus ? * C.
      maculata ?). Amplification with WY1 yielded the opposite results. Then, 30
      individuals per fish were randomized to verify the primers, and the results
      showed that the primers were specific for breeds, as intended. The specific
      primers can not only simply distinguish between two kinds of hybrids, but also
      rapidly identify the two parents. This study provides a method of molecular
      marker identification to identify reciprocal hybrids.

PMID- 24438306
TI  - The complete mitochondrial genome of Mongolian redfin, Chanodichthys mongolicus
      (Cypriniformes: Cyprinidae): genome description and related phylogenetic
      analyses.
AB  - Chanodichthys mongolicus is a ferocious carnivorous species in the family
      Cyprinidae, which has a high economic value in freshwater aquaculture species. In
      the present study, we report the complete mitochondrial genome of C. mongolicus,
      comparing with two different individuals of C. mongolicus and phylogenetic
      analysis with closely related species. The complete mitochondrial genome of C.
      mongolicus was 16,622 bp, and it contained 13 protein-coding genes, 2 rRNA genes,
      22 tRNA genes, a control region (D-loop) and an L-strand replication origin (OL).
      It revealed that D-loop, ND4, ND5 and CYTB may be markers for studying
      conservation genetics and population genetics.

PMID- 24438307
TI  - The complete mitochondrial genome of the bank vole Clethrionomys glareolus
      (Rodentia: Arvicolinae).
AB  - We present the first complete sequence of the bank vole (Clethrionomys glareolus)
      mitochondrial genome (GenBank accession no. KF918859). The bank vole mitogenome
      is 16,353 base pairs long and shows the gene content, genome architecture and
      gene strand asymmetry typical for mammals. The sequence provides an important new
      genomic resource for the bank vole, which is a popular study species in
      ecological and evolutionary research. 

PMID- 24438308
TI  - Mitochondrial DNA variation in the East China Sea and Yellow Sea populations of
      swimming crab Ovalipes punctatus.
AB  - Swimming crab Ovalipes punctatus is a commercially important species in the East
      China Sea and Yellow Sea, but there is limited knowledge of its genetic
      population structure. The population genetic structure of O. punctatus in East
      China Sea and Yellow Sea was examined with a 658-bp segment of the mtDNA COI
      gene. A total of 60 individuals were collected from five locations and 48
      haplotypes were obtained. Mean haplotype diversity and nucleotide diversity for
      the five populations were 0.9876 +/- 0.0068 and 0.0074 +/- 0.0041, respectively.
      Analysis of molecular variance (AMOVA) detected no significant differences at all
      hierarchical levels, and all FST values were non-significant, indicating that no
      significant population genetic structure exists in the East China Sea and Yellow
      Sea. These results supported the null hypothesis that O. punctatus within the
      East China Sea and Yellow Sea constitutes a panmictic mtDNA gene pool. Neutrality
      tests and mismatch distribution supported population expansion in this species,
      indicating that climate change could play an important role in affecting the
      demographic history of marine species. Strong dispersal capacity of larvae and
      adults, and ocean currents in the studied area could be the reasons for genetic
      homogeneity in this species in the East China Sea and Yellow Sea. Another
      explanation for the lack of phylogeographic structure in O. punctatus might
      reflect a recent range expansion after the last glacial maximum and insufficient
      time to attain migration-drift equilibrium.

PMID- 24438309
TI  - The complete mitochondrial genome of Tetrancistrum nebulosi (Monogenea:
      Ancyrocephalidae).
AB  - The first complete mitochondrial (mt) genome of Ancyrocephalidae is reported
      herein. The mt genome of Tetrancistrum nebulosi was 13,392 bp in length
      containing 12 protein-coding genes (lacking atp8), 22 tRNA genes and 2 rRNA
      genes. The longest non-coding region was located between nad5 and trnG, and the A
      + T content was 72.4%. All tRNAs had the typical clover-leaf secondary structure
      except for trnS1((AGN)), trnR, trnF and trnQ. The rrnL and rrnS subunits were
      separated by trnC, as documented in the monopisthocotylean groups (Benedenia and
      Gyrodactylus species), while they were adjacent to each other in the
      polyopisthocotylean species (Microcotyle sebastis, Polylabris halichoeres and
      Pseudochauhanea macrorchis).

PMID- 24438310
TI  - Evolution of mitochondrial DNA and its relation to basal metabolic rate.
AB  - Energy metabolism is essential for the survival of animals, which can be
      characterized by maximum metabolic rate (MMR) and basal metabolic rate (BMR).
      Because of the crucial roles of mitochondria in energy metabolism, mitochondrial
      DNA (mtDNA) has been subjected to stronger purifying selection in strongly
      locomotive than weakly locomotive birds and mammals. Although maximum locomotive
      speed (an indicator of MMR) showed a negative correlation with the evolutionary
      rate of mtDNA, it is unclear whether BMR has driven the evolution of mtDNA. Here,
      we take advantage of the large amount of mtDNA and BMR data in 106 mammals to
      test whether BMR has influenced the mtDNA evolution. Our results showed that, in
      addition to the locomotive speed, mammals with higher BMR have subjected to
      stronger purifying selection on mtDNA than did those with lower BMR. The
      evolution of mammalian mtDNA has been modified by two levels of energy
      metabolism, including MMR and BMR. Our study provides a more comprehensive view
      of mtDNA evolution in relation to energy metabolism. 

PMID- 24438311
TI  - The complete mitochondrial genome sequence of Silver Gudgeon (Gnathopogon
      argentatus).
AB  - The complete mitochondrial genome of Gnathopogon argentatus was determined to be
      16,607 bp long circular molecule with a typical gene arrangement of vertebrate
      mitochondrial DNA. The complete mitochondrial genome of G. argentatus is 16,607
      bp in length with 56.02% AT content, including 13 protein-coding genes, 22 tRNA
      genes, 2 rRNA genes and 1 control region. The complete mitochondrial genome of G.
      argentatus was obtained for the first time and would play an important role in
      population structure and conservation genetic studies.

PMID- 24438312
TI  - The complete mitochondrial genome sequence of the Chinese Serow, Capricornis
      milneedwardsii (Cetartiodactyla: Caprinae).
AB  - The Chinese Serow (Capricornis milneedwardsii) is a native species distributed in
      China and Southeast Asia, and has been listed as one of the Class II national
      protected species in China. Here we first determined and annotated its complete
      mitochondrial genome. The mito-genome of Chinese Serow is 16,444 bp in length,
      consisting of two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, 13
      protein-coding genes, and one control region. The overall base composition is A:
      33.5%, T: 26.7%, C: 26.6%, and G: 13.2%, with a much higher A + T content.

PMID- 24438313
TI  - The complete mitochondrial genome sequence of Pampus argenteus (Perciformes:
      Stromateidae).
AB  - In this study, we sequenced and annotated the complete mitochondrial genome of
      Pampus argenteus (Perciformes: Stromateidae). The mitogenome is 17,098 bp in
      length, which contains 13 protein-coding genes, 2 rRNA genes, 23 tRNA genes and 2
      non-coding regions: origin of light-strand replication (OL) and control region (D
      loop). The overall nucleotide base composition of P. argenteus mtDNA is A 30.35%,
      C 25.55%, G 15.28% and T 28.82%, with an A + T content of 59.17%. Except for ND6
      gene and eight tRNA genes, all other mitochondrial genes were encoded on the
      heavy strand. The mitochondrial genome of P. argenteus may be helpful to the
      studies on conservation genetics and stock evaluation of P. argenteus resource,
      as well as molecular phylogeny and species identification of Stromateidae.

PMID- 24438314
TI  - Identification of mammalian species using the short and highly variable regions
      of mitochondrial DNA.
AB  - The mitochondrial DNA (mtDNA) typing is useful for the species determination of
      degraded samples and the nucleotide diversity of target fragments across species
      is crucial for the discrimination. In this study, the short and highly
      polymorphic regions flanked by two conserved termini were sought by the sequence
      alignment of mtDNA across species and two target regions located at 12S rRNA gene
      were characterized. Two universal primer sets were developed that appear to be
      effective for a wide variety of mammalian species, even for domestic birds. The
      two target regions could be efficiently amplified using their universal primer
      sets on degraded samples and provide sufficient information for species
      determination. Therefore, the two short and highly variable target regions might
      provide a high discriminative capacity and should be suitable for the species
      determination of degraded samples. 

PMID- 24438315
TI  - Serum peptide mapping in gastric precancerous lesion and cancer.
AB  - OBJECTIVE: To construct and verify a diagnostic model using proteomic analysis of
      serum samples for identifying gastric precancerous lesions and gastric cancer
      (GC). METHODS: The serum samples from 25 patients with gastric precancerous
      lesions (chronic atrophic gastritis with mild to moderate dysplasia), 25 GC
      patients and 25 healthy controls were analyzed using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Spectral
      peaks with significant difference among the groups were identified and used as a
      diagnostic model for detecting gastric precancerous lesions and GC. The serum
      peptide map model was validated using an independent sample set including 15
      healthy volunteers, 15 precancerous and 15 GC patients. RESULTS: The spectral
      peaks for the peptides with mass-to-charge (m/z) values of 1741 and 4210 were the
      most significantly different among the three groups. The sensitivity of this
      diagnostic model for detecting healthy controls, patients with gastric
      precancerous lesions and patients with GC was 80.0% (12/15), 66.7% (10/15) and
      66.7% (10/15) respectively, while the specificity was 66.7% (20/30), 73.3%
      (22/30) and 73.3% (22/30), respectively. CONCLUSION: Our diagnostic model is
      useful for diagnosing gastric precancerous lesions and GC.

PMID- 24438316
TI  - An actor-partner interdependence analysis of associations between affect and
      parenting behavior among couples.
AB  - Prior studies evaluating associations between parental affect and parenting
      behavior have typically focused on either mothers or fathers despite evidence
      suggesting that affect and parenting behavior may be interdependent among
      couples. This study addressed this gap in the literature by evaluating
      associations between self-reported affect and parenting behavior using an actor
      partner interdependence analysis among a sample of 53 mother-father dyads of 3-
      to 5-year-old children. Results suggested that mothers' and fathers' negative
      affect, as well as mothers' and fathers' positive affect, were positively
      associated. Both mothers' and fathers' negative affect were negatively associated
      with fathers' positive affect. Mothers' and fathers' harsh/negative parenting
      behavior, and supportive/engaged parenting behavior, were positively associated.
      Furthermore, mothers' negative affect was positively associated with mothers' and
      fathers' harsh/negative parenting behavior while mothers' positive affect was
      negatively associated with mothers' harsh/negative behavior and positively
      associated with mothers' supportive/engaged behavior. Fathers' negative affect
      was positively associated with fathers' supportive/engaged parenting behavior,
      while fathers' positive affect was positively associated with mothers' and
      fathers' supportive/engaged behavior. Results highlight the importance of
      conceptualizing and measuring characteristics of both mothers and fathers, if
      applicable, when researching the dynamics of interpersonal relationships within
      families.

PMID- 24438317
TI  - Upscaling human papillomavirus vaccination in high-income countries: impact
      assessment based on transmission model.
AB  - BACKGROUND: The decrease in human papillomavirus (HPV) vaccine prices may allow
      upscale already started vaccination programmes but the advantages of different
      options are unclear. METHODS: Using a mathematical model of HPV16 and 18
      transmission and data on vaccination coverage from Italy, we compared 3 options
      to upscale an already started programme targeting 11-year old girls (coverage
      65%): a) coverage improvement (from 65% to 90%); b) addition of 11-year-old boys
      (coverage 65%); or c) 1-year catch-up of older girls (coverage 50%). RESULTS: The
      reduction of cervical HPV16/18 infection as compared to no vaccination (i.e.
      effectiveness against HPV16/18) increased from 76% to 98% with coverage
      improvement in girls and to 90% with the addition of boys. With higher coverage
      in girls, HPV16/18 infection cumulative probability by age 35 decreased from 25%
      to 8% with a 38% increase in vaccine number. The addition of boys decreased the
      cumulative probability to 18% with a 100% increase in the number of vaccinees.
      For any coverage in girls, the number of vaccinees to prevent 1 woman from being
      infected by HPV16/18 by age 35 was 1.5, whereas it was 2.7 for the addition of
      boys. Catch-up of older girls only moved forward the vaccination effectiveness by
      2-5 years. CONCLUSIONS: Increasing vaccination coverage among girls is the most
      effective option for decreasing HPV16/18. If not achievable, vaccinating boys is
      justifiable if vaccine cost has at least halved, because this option would almost
      double the number of vaccinees.

PMID- 24438318
TI  - Low plasma levels of antithrombin III in the early post-operative period
      following pediatric liver transplantation: should they be replaced? A single
      center pilot study.
AB  - eHAT after LT remains a life-threatening complication. In the majority of
      anticoagulation protocols, heparin is used to prevent thromboses. Our study aimed
      to monitor AT-III levels in the early post-LT period to assess the need for the
      administration of AT-III concentrate to ensure the effectiveness of heparin. We
      monitored coagulation daily by measuring INR, APTT, fibrinogen, platelets, and AT
      III. Anticoagulation therapy consisted of LMWH, AT-III, and dipyridamole. AT-III
      concentrate was administered when AT-III activity was <=60%. DUS was performed
      daily for the first five post-operative days or whenever vascular thrombosis was
      suspected. Between October 2007 and October 2011, 39 LT were performed in our
      center. The median age was 26 months (6-196) with a median weight of 9 kg (5.5
      49). AT-III activity was <=60% in 27 patients. Lower levels were particularly
      observed in partial grafts and recipients weighing less than 10 kg. Patent
      arterial flow was present in all 39 LT during the first five post-operative days.
      AT-III levels were low in 70% of pediatric patients following LT, thereby risking
      heparin ineffectiveness. These results may implicate low AT-III levels in the
      etiology of eHAT post-LT. However, this is a small single-center pilot study and
      further larger prospective trials are required to confirm these results.

PMID- 24438319
TI  - Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to
      denosumab therapy.
AB  - Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to
      be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local
      growth and recurrences are common and therapeutic options may be limited due to
      the vicinity of crucial structures. We describe a case of a locally aggressive,
      multinucleated giant cell-containing lesion of the forearm of a 21-year old
      woman, treated with denosumab for recurrent, surgically uncontrollable disease.
      Under the influence of this RANKL inhibitor, the tumor showed a marked reduction
      of the content of the osteoclastic giant cells and an extensive metaplastic
      osteoid production leading to the bony containment, mostly located
      intracortically in the proximal radius. The diagnosis of a periosteal ABC was
      confirmed by FISH demonstrating USP6 gene rearrangement on the initial biopsy.
      Function conserving surgery could be performed, enabling reconstruction of the
      affected bone. Inhibition of RANKL with denosumab may offer therapeutic option
      for patients not only with giant cell tumors but also with ABCs. 

PMID- 24438320
TI  - Novel regulatory roles of omega-3 fatty acids in metabolic pathways: a proteomics
      approach.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been shown to
      alleviate the symptoms of metabolic disorders, such as heart disease, diabetes,
      obesity and insulin resistance. Several putative mechanisms by which n-3 PUFA
      elicit beneficial health effects have been proposed; however, there is still a
      shortage of knowledge on the proteins and pathways that are regulated by n-3
      PUFA. METHODS: Using two dimensional polyacrylamide gel electrophoresis (2D-PAGE)
      and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we
      investigated the effects of diets high or low in n-3 PUFA on hepatic proteomic
      profile of C57BL/6 mice. RESULTS: The findings show for the first time that high
      dietary n-3 PUFA reduced the expression of regucalcin, adenosine kinase and
      aldehyde dehydrogenase. On the other hand, diets high in n-3 PUFA increased the
      expression of apolipoprotein A-I, S-adenosylmethionine synthase, fructose-1, 6
      bisphosphatase, ketohexokinase, malate dehydrogenase, GTP-specific succinyl CoA
      synthase, ornithine aminotransferase and protein disulfide isomerase-A3.
      CONCLUSIONS: Our findings revealed for the first time that n-3 PUFA causes
      alterations in several novel functional proteins involved in regulating lipid,
      carbohydrate, one-carbon, citric acid cycle and protein metabolism, suggesting
      integrated regulation of metabolic pathways. These novel proteins are potential
      targets to develop therapeutic strategies against metabolic disorders.

PMID- 24438321
TI  - A pilot study of the use of EEG-based synchronized Transcranial Magnetic
      Stimulation (sTMS) for treatment of Major Depression.
AB  - BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective
      treatment for Major Depressive Disorder (MDD), and is based upon delivery of
      focal high-energy pulses of electromagnetic stimulation. We postulated that
      delivery of rTMS at the subject's individual alpha frequency (synchronized TMS,
      or sTMS) would achieve efficacy with lower energy of stimulation. We developed a
      device that rotates neodymium cylindrical magnets at three locations along the
      midline above the subject's scalp to impart low-energy, sinusoidal-waveform
      magnetic brain stimulation over a broad area, and performed this efficacy study.
      METHOD: Fifty-two subjects with MDD were enrolled in a randomized, sham
      controlled, double-blind treatment study (Trial Registration: NCT01683019). Forty
      six subjects were included in the final analysis. Most subjects received
      concurrent antidepressant medications that remained unchanged during the study.
      Subjects were randomized to three treatment groups: 1) active sTMS with a fixed
      frequency at the subject's alpha frequency; 2) active sTMS with a random stimulus
      frequency that varied between 8 Hz and 13 Hz; and, 3) sham sTMS. 20 half-hour
      sTMS sessions were administered 5 days per week for 4 weeks. RESULTS: Subjects
      with either fixed or random frequency active sTMS had statistically significantly
      greater percentage reduction in depression severity compared to sham (48.5% vs.
      19.3%, respectively; p = 0.001). No significant difference was found between
      fixed and random groups (p = 0.30). No significant side effects were reported.
      CONCLUSIONS: These results suggest that sTMS may be an effective treatment for
      MDD.

PMID- 24438322
TI  - Potential anti-osteoporotic effects of herbal extracts on osteoclasts,
      osteoblasts and chondrocytes in vitro.
AB  - BACKGROUND: Osteoporosis (OP) is one of the most serious diseases in the modern
      world, and OP patients frequently suffer from fragility fractures in the hip,
      spine and wrist, resulting in a limited quality of life. Although bisphosphonates
      (BPs) are the most effective class of anti-bone-resorptive drugs currently
      available and the most commonly prescribed for the clinical treatment of OP, they
      are known to cause serious side effects such as bisphosphonate-related
      osteonecrosis of the jaw. Novel therapeutic materials that can replace the use of
      BPs have therefore been developed. METHODS: We commenced an institutional
      collaborative project in which candidates of herbal extracts were selected from
      more than 400 bioactive herbal products for their potential therapeutic effects
      not only in OP, but also in oral and skeletal diseases. In the present study, we
      report on 3 Chinese medical herbal extracts from the root barks of Melia
      azedarach, Corydalis turtschaninovii, and Cynanchum atratum. RESULTS: All of
      these extracts inhibited osteoclast proliferation and induced apoptosis by up
      regulation of caspase activity and increase of mitochondrial pro-apoptotic
      proteins expression. Furthermore, the extracts enhanced differentiation, but did
      not affect proliferation of both osteoblasts and chondrocytes. The osteo
      inducible effect was also observed in cultured primary bone marrow cells.
      CONCLUSIONS: Although these extracts have been utilized in traditional Chinese
      medicine for hundreds of years, there are no reports to our knowledge, on their
      therapeutic effects in OP. In this study, we elucidate the potency of these
      herbal extracts as novel candidates for OP therapy.

PMID- 24438323
TI  - Molecular epidemiology and antifungal susceptibility of Serbian Cryptococcus
      neoformans isolates.
AB  - Molecular typing and antifungal susceptibility testing of 34 clinical Serbian
      Cryptococcus neoformans isolates from 25 patients was retrospectively performed.
      Amplified fragment length polymorphism (AFLP) fingerprinting was used for
      genotyping, whereas a novel real-time PCR was used to determine the mating- and
      serotype. The antifungals amphotericin B, 5-fluorocytosine, fluconazole,
      voriconazole, itraconazole and posaconazole were used to determine the antifungal
      susceptibility profiles. The majority of isolates belonged to genotype AFLP1/VNI
      (n = 20; 58.8%), followed by AFLP2/VNIV (n = 10; 29.4%), AFLP3/VNIII (n = 3;
      8.8%) and AFLP1B/VNII (n = 1; 2.9%). All AFLP1/VNI isolates were mating-serotype
      alphaA, the sole AFLP1B/VNII isolate was found to be aA, whereas AFLP2/VNIV
      harboured serotype D isolates with either the a (n = 2; 5.9%) or alpha (n = 8;
      23.5%) mating-type allele. The isolates (n = 3; 8.8%) that were found to be
      genotype AFLP3/VNIII had the hybrid mating- and serotype combination aA-alphaD.
      In vitro antifungal susceptibility testing showed that all isolates were
      susceptible to amphotericin B, voriconazole and posaconazole. Low resistance
      level was observed for fluconazole (n = 1; 2.9%) and 5-fluorocytosine. (n = 2;
      5.8%). A large percentage of isolates was found to be susceptible dose dependent
      to itraconazole (n = 16; 47.1%). AFLP1/VNI was the most common genotype among
      clinical C. neoformans isolates from immunocompromised patients in Serbia. C.
      neoformans from HIV-negative patients were significantly less susceptible to 5
      fluorocytosine (P < 0.01). Correlation between genotypes and antifungal
      susceptibility was not observed. 

PMID- 24438324
TI  - Hypoplastic left heart with intact atrial septum and levoatriocardinal vein: a
      challenge in identifying aortic arch branches.
AB  - The levoatriocardinal vein provides alternative egress from the left atrium to
      the systemic veins in left-sided obstructive lesions. Although rare, it has been
      described in association with hypoplastic left heart syndrome. We report a case
      of hypoplastic left heart syndrome with levoatriocardinal vein and aberrant right
      subclavian artery where cardiac magnetic resonance imaging/angiography proved to
      be a valuable imaging modality for pre-operative evaluation. 

PMID- 24438325
TI  - Physical characterization of titanium dioxide nanoparticles.
AB  - OBJECTIVE: The objective of this study was to review six measurement methods (X
      ray line broadening, electron microscopy, static light scattering, dynamic light
      scattering, X-ray sedimentation and surface area determination), which are widely
      used for the characterization of ultrafine inorganic oxides used in cosmetic
      formulations. Depending on the processing that they have received and the system
      in which they are examined, these oxides can exist as primary particles, strongly
      bound aggregates or weakly bound agglomerates. METHODS: The example of titanium
      dioxide, TiO2 , is used to consider which type of particle is being measured in a
      particular case, and the factors which influence the 'size' that is generated by
      a particular method. Where appropriate, a correlation is made between results of
      different measurements. RESULTS: Results for a particular set of four cosmetic
      grade TiO2 's are presented and examined, in the context of a much broader set of
      measurements taken from the scientific literature. CONCLUSION: In general, X-ray
      line broadening, electron microscopy and surface area measurements led to
      estimates of the size of primary particles. By contrast, both sedimentation and
      light scattering measurements measured the size of the secondary particles, and
      the figures which were generated depended on the dispersion conditions used for
      preparation of the measurement samples. For poorly dispersed or lightly milled
      samples, the size may be dominated by the presence of weakly bound agglomerates,
      but even when the sample is well dispersed or heavily milled, the reported size
      cannot be less than that of the aggregates.

PMID- 24438326
TI  - Curcumin-enhanced chemosensitivity of FDA-approved platinum (II)-based anti
      cancer drugs involves downregulation of nuclear endonuclease G and NF-kappaB as
      well as induction of apoptosis and G2/M arrest.
AB  - Curcumin, an active natural compound in turmeric and curry, has been reported to
      exhibit anti-cancer effect. Cisplatin, carboplatin and oxaliplatin are used to
      treat various types of cancers. However, acquired resistance and toxicities are
      observed. Here, the addition of curcumin significantly increased cytotoxicity of
      the anti-cancer drugs on human colorectal cancer HT-29 cells, producing
      synergistic (cisplatin and carboplatin) and additivity (oxaliplatin) effects.
      Treatments in combination with curcumin resulted in a significantly increased
      induction of apoptosis and occurrence of G2/M arrest. Nuclear apoptosis-inducing
      factor (AIF), EndoG and NF-kappaB were elevated by anti-cancer drugs, suggesting
      the involvement of AIF and EndoG. The addition of curcumin suppressed nuclear AIF
      and EndoG and reversed anti-cancer drugs-induced NF-kappaB expression, suggesting
      the association of EndoG and NF-kappaB in curcumin-enhanced chemosensitivity.
      Therefore, the intake of foods rich in curcumin or curcumin-containing
      supplements should be taken into consideration for patients receiving
      chemotherapy to optimize the outcome of treatments.

PMID- 24438327
TI  - Extracellular domains play different roles in gap junction formation and docking
      compatibility.
AB  - GJ (gap junction) channels mediate direct intercellular communication and play an
      important role in many physiological processes. Six connexins oligomerize to form
      a hemichannel and two hemichannels dock together end-to-end to form a GJ channel.
      Connexin extracellular domains (E1 and E2) have been shown to be important for
      the docking, but the molecular mechanisms behind the docking and formation of GJ
      channels are not clear. Recent developments in atomic GJ structure and functional
      studies on a series of connexin mutants revealed that E1 and E2 are likely to
      play different roles in the docking. Non-covalent interactions at the docking
      interface, including hydrogen bonds, are predicted to form between interdocked
      extracellular domains. Protein sequence alignment analysis on the docking
      compatible/incompatible connexins indicate that the E1 domain is important for
      the formation of the GJ channel and the E2 domain is important in the docking
      compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming
      or equivalent residues in both E1 and E2 domains are mutational hot spots for
      connexin-linked human diseases. Understanding the molecular mechanisms of GJ
      docking can assist us to develop novel strategies in rescuing the disease-linked
      connexin mutants. 

PMID- 24438328
TI  - TALE proteins bind to both active and inactive chromatin.
AB  - TALE (transcription activator-like effector) proteins can be tailored to bind to
      any DNA sequence of choice and thus are of immense utility for genome editing and
      the specific delivery of transcription activators. However, to perform these
      functions, they need to occupy their sites in chromatin. In the present study, we
      have systematically assessed TALE binding to chromatin substrates and find that
      in vitro TALEs bind to their target site on nucleosomes at the more accessible
      entry/exit sites, but not at the nucleosome dyad. We show further that in vivo
      TALEs bind to transcriptionally repressed chromatin and that transcription
      increases binding by only 2-fold. These data therefore imply that TALEs are
      likely to bind to their target in vivo even at inactive loci.

PMID- 24438330
TI  - Supramolecular membrane-associated assemblies of RNA metabolic proteins in
      Escherichia coli.
AB  - Controlled RNA degradation is known to be achieved via the exosome in Eukarya and
      Archaea, and the RNA degradosome in Bacteria. In this issue of the Biochemical
      Journal, Taghbalout et al. demonstrate in Escherichia coli that many additional
      proteins of the RNA degradation and processing network co-localize with the RNA
      degradosome in supramolecular structures. The latter appear as extended
      cytoplasmic membrane-associated assemblies that coil around the periphery of the
      cell when visualized by immunofluorescence microscopy. The co-localizing ensemble
      of RNA metabolic proteins includes RNaseE, PNPase (polynucleotide phosphorylase),
      the DEAD-box RNA helicase RhlB, the oligo-RNase Orn, RNases II and III, PAP I
      [poly(A) polymerase I], RppH (RNA pyrophosphohydrolase), proteins RraA and RraB
      that are negative regulators of RNaseE, and the RNA chaperone Hfq. Not all
      cellular RNA-binding proteins associate with these structures, as shown for EF-Tu
      (elongation factor Tu) and Rho helicase. Formation of the supramolecular
      architecture was shown to not be dependent on two other known cytoskeletal
      systems or on RNA de novo synthesis or nucleoid positioning within the cell. This
      novel dimension of compartmentalization in bacteria that lack classic cell
      compartments opens new perspectives on how RNA homoeostasis is achieved,
      organized and regulated in bacteria such as E. coli. 

PMID- 24438331
TI  - Implant counseling and information: questions, predictors, and decision-making of
      patients before implant therapy.
AB  - BACKGROUND: Implant counseling and information must enable the patient to make
      his/her own independent decision (informed consent). However, there are
      indications that patient counseling and information often provides incomplete
      information. METHODS: In 40 implant counseling and information sessions, all
      questions raised by the patients were documented during the session. The
      patient's decision for or against implant therapy was recorded 3 months later.
      The influence of the patient's age and gender, the type of insurance, the number
      of questions asked by the patient, the number of required implants, and the need
      for augmentation on the patient's decision were determined. RESULTS: Sixty-five
      percentage of the patients decided in favor of implant-prosthetic therapy. One
      significant factor influencing the patient's decision was the need for
      augmentation. Fifty-four percentage of the patients who decided in favor of the
      implant intervention needed augmentation. Eighty-six percentage of the patients
      who refused the intervention could have been treated only in conjunction with pre
      implantological augmentation. The need for augmentation was associated with a
      higher mean number of questions per counseling and information session (3.7 vs.
      2.3) (n.s.). Patients who had opted for implant treatment asked significantly
      fewer questions (2.5) than patients who refused the treatment (4.4). The
      patient's age and gender, the type of insurance, or the number of implants
      required had no influence on decision-making. CONCLUSION: Patients who ask many
      questions rather tend to refuse the implant treatment. The need for augmentation
      was also associated with a significantly higher percentage of implant refusal.
      These results suggest that patients with an indication of augmentation require
      particularly detailed and comprehensive counseling and information.

PMID- 24438333
TI  - Multimedia educational interventions for consumers about prescribed and over-the
      counter medications.

PMID- 24438334
TI  - Use of digital photographic maps for Mohs micrographic surgery.

PMID- 24438332
TI  - Genome characteristics reveal the impact of lichenization on lichen-forming
      fungus Endocarpon pusillum Hedwig (Verrucariales, Ascomycota).
AB  - BACKGROUND: Lichen is a classic mutualistic organism and the lichenization is one
      of the fungal symbioses. The lichen-forming fungus Endocarpon pusillum is living
      in symbiosis with the green alga Diplosphaera chodatii Bialsuknia as a lichen in
      the arid regions. RESULTS: 454 and Illumina technologies were used to sequence
      the genome of E. pusillum. A total of 9,285 genes were annotated in the 37.5 Mb
      genome of E. pusillum. Analyses of the genes provided direct molecular evidence
      for certain natural characteristics, such as homothallic reproduction and drought
      tolerance. Comparative genomics analysis indicated that the expansion and
      contraction of some protein families in the E. pusillum genome reflect the
      specific relationship with its photosynthetic partner (D. chodatii). Co-culture
      experiments using the lichen-forming fungus E. pusillum and its algal partner
      allowed the functional identification of genes involved in the nitrogen and
      carbon transfer between both symbionts, and three lectins without signal peptide
      domains were found to be essential for the symbiotic recognition in the lichen;
      interestingly, the ratio of the biomass of both lichen-forming fungus and its
      photosynthetic partner and their contact time were found to be important for the
      interaction between these two symbionts. CONCLUSIONS: The present study lays a
      genomic analysis of the lichen-forming fungus E. pusillum for demonstrating its
      general biological features and the traits of the interaction between this fungus
      and its photosynthetic partner D. chodatii, and will provide research basis for
      investigating the nature of its drought resistance and symbiosis.

PMID- 24438335
TI  - Association between serological evidence of past Coxiella burnetii infection and
      atherosclerotic cardiovascular disease in elderly patients.
AB  - Q fever, caused by Coxiella burnetii, may cause vascular complications, but the
      role that this infection may play in the development of atherosclerotic
      cardiovascular disease remains unknown. This study examined the association
      between Q fever serology and cardiovascular disease in a region where Q fever is
      endemic. A case-control study was conducted in the Hospital Universitario de
      Burgos (Spain) between February 2011 and June 2012. A total of 513 samples were
      tested, from 454 hospitalized patients >=65 years old, of whom 164 were cases
      (patients with prevalent or incident coronary heart, cerebrovascular or
      peripheral artery, disease) and 290 controls (patients without cardiovascular
      disease). Serum IgG antibody phase II titres against Q fever were determined by
      immunofluorescence assay. Seropositivity (titres >=1:256) was detected in 84/164
      (51.2%) cases and in 109/290 (37.6%) controls (p = 0.005; OR, 1.7; 95% CI, 1.1
      2.5). This ratio increases when adjusted for sex, hypertension, dyslipidaemia,
      smoking, diabetes and atrial fibrillation (OR, 2.6; 95% CI, 1.5-4.7). The
      geometric mean titre (GMT) for C. burnetii phase II assay was higher in cases
      than in controls (p = 0.004). We found no significant relationship between
      cardiovascular disease and C. pneumoniae, and Cytomegalovirus seropositivity
      (both determined by the IgG ELISA method). In conclusion, serological evidence of
      past Q fever is associated with atherosclerotic cardiovascular disease in elderly
      patients in an endemic region.

PMID- 24438337
TI  - High feeding intensity increases the severity of fatty liver in the American mink
      (Neovison vison) with potential ameliorating role for long-chain n-3
      polyunsaturated fatty acids.
AB  - BACKGROUND: Rapid body fat mobilization, obesity, and an inadequate supply of n-3
      polyunsaturated fatty acids (PUFA) have been suggested to play roles in the
      etiology of fatty liver in the American mink (Neovison vison). This study
      examined the effects of feeding intensity and dietary fat source on fatty liver
      induced by fasting. In a multi-factorial design, 3 different fat sources (herring
      oil, rich in n-3 PUFA, soya oil, rich in n-6 PUFA, and canola oil, rich in n-9
      monounsaturated fatty acids) were fed to mink at a low and high feeding intensity
      for 10 weeks, followed by an overnight or a 5-day fasting treatment to induce
      fatty liver. RESULTS: Fasting led to the development of fatty liver with
      increased severity in the mink fed at the high feeding intensity. The herring oil
      diet, high in long-chain n-3 PUFA, was found to decrease the severity of fatty
      liver in the mink at the high feeding intensity. CONCLUSION: Preventing excessive
      weight gain and increasing dietary intake of n-3 long-chain PUFA may help prevent
      excessive lipid accumulation during prolonged periods of fasting or inappetence
      by promoting hepatic fatty acid oxidation.

PMID- 24438336
TI  - Congenital toxoplasmosis and prenatal care state programs.
AB  - BACKGROUND: Control programs have been executed in an attempt to reduce vertical
      transmission and the severity of congenital infection in regions with a high
      incidence of toxoplasmosis in pregnant women. We aimed to evaluate whether
      treatment of pregnant women with spiramycin associated with a lack of monitoring
      for toxoplasmosis seroconversion affects the prognosis of patients. METHODS: We
      performed a prospective cohort study with 246 newborns (NB) at risk for
      congenital toxoplasmosis in Goiania (Brazil) between October 2003 and October
      2011. We analyzed the efficacy of maternal treatment with spiramycin. RESULTS: A
      total of 40.7% (66/162) of the neonates were born seriously infected. Vertical
      transmission associated with reactivation during pregnancy occurred in 5.5%
      (9/162) of the NB, with one showing severe infection (systemic). The presence of
      specific immunoglobulins (fetal IgM and NB IgA) suggested the worst prognosis.
      Treatment of pregnant women by spiramycin resulted in reduced vertical
      transmission. When infected pregnant women did not undergo proper treatment, the
      risk of severe infection (neural-optical) in NB was significantly increased.
      Fetal IgM was associated with ocular impairment in 48.0% (12/25) of the fetuses
      and neonatal IgA-specific was related to the neuro-ophthalmologic and systemic
      forms of the disease. When acute toxoplasmosis was identified in the postpartum
      period, a lack of monitoring of seronegative pregnant women resulted in a higher
      risk of severe congenital infection. CONCLUSION: Treatment of pregnant women with
      spiramycin reduces the possibility of transmission of infection to the fetus.
      However, a lack of proper treatment is associated with the onset of the neural
      optical form of congenital infection. Primary preventive measures should be
      increased for all pregnant women during the prenatal period and secondary
      prophylaxis through surveillance of seroconversion in seronegative pregnant woman
      should be introduced to reduce the severity of congenital infection in the
      environment.

PMID- 24438338
TI  - Myostatin augments muscle-specific ring finger protein-1 expression through an NF
      kB independent mechanism in SMAD3 null muscle.
AB  - Smad (Sma and Mad-related protein) 2/3 are downstream signaling molecules for TGF
      beta and myostatin (Mstn). Recently, Mstn was shown to induce reactive oxygen
      species (ROS) in skeletal muscle via canonical Smad3, nuclear factor-kappaB, and
      TNF-alpha pathway. However, mice lacking Smad3 display skeletal muscle atrophy
      due to increased Mstn levels. Hence, our aims were first to investigate whether
      Mstn induced muscle atrophy in Smad3(-/-) mice by increasing ROS and second to
      delineate Smad3-independent signaling mechanism for Mstn-induced ROS. Herein we
      show that Smad3(-/-) mice have increased ROS levels in skeletal muscle, and
      inactivation of Mstn in these mice partially ablates the oxidative stress.
      Furthermore, ROS induction by Mstn in Smad3(-/-) muscle was not via nuclear
      factor-kappaB (p65) signaling but due to activated p38, ERK MAPK signaling and
      enhanced IL-6 levels. Consequently, TNF-alpha, nicotinamide adenine dinucleotide
      phosphate oxidase, and xanthine oxidase levels were up-regulated, which led to an
      increase in ROS production in Smad3(-/-) skeletal muscle. The exaggerated ROS in
      the Smad3(-/-) muscle potentiated binding of C/EBP homology protein transcription
      factor to MuRF1 promoter, resulting in enhanced MuRF1 levels leading to muscle
      atrophy. 

PMID- 24438341
TI  - "It's complicated": collective memories of transgender, queer, and questioning
      youth in high school.
AB  - Using the qualitative participatory action methodology, collective memory work,
      this study explored how transgender, queer, and questioning (TQQ) youth make
      meaning of their sexual orientation and gender identity through high school
      experiences. Researchers identified three major conceptual but overlapping themes
      from the data generated in the transgender, queer, and questioning youth focus
      group: a need for resilience, you should be able to be safe, and this is what
      action looks like! The researchers discuss how as a research product, a
      documentary can effectively "capture voices" of participants, making research
      accessible and attractive to parents, practitioners, policy makers, and
      participants. 

PMID- 24438339
TI  - Multiparameter screening reveals a role for Na+ channels in cytokine-induced beta
      cell death.
AB  - Pancreatic beta-cell death plays a role in both type 1 and type 2 diabetes, but
      clinical treatments that specifically target beta-cell survival have not yet been
      developed. We have recently developed live-cell imaging-based, high-throughput
      screening methods capable of identifying factors that modulate pancreatic beta
      cell death, with the hope of finding drugs that can intervene in this process. In
      the present study, we used a high-content screen and the Prestwick Chemical
      Library of small molecules to identify drugs that block cell death resulting from
      exposure to a cocktail of cytotoxic cytokines (25 ng/mL TNF-alpha, 10 ng/mL IL
      1beta, and 10 ng/mL IFN-gamma). Data analysis with self-organizing maps revealed
      that 19 drugs had profiles similar to that of the no cytokine condition,
      indicating protection. Carbamazepine, an antiepileptic Na(+) channel inhibitor,
      was particularly interesting because Na(+) channels are not generally considered
      targets for antiapoptotic therapy in diabetes and because the function of these
      channels in beta-cells has not been well studied. We analyzed the expression and
      characteristics of Na(+) currents in mature beta-cells from MIP-GFP mice. We
      confirmed the dose-dependent protective effects of carbamazepine and another use
      dependent Na(+) channel blocker in cytokine-treated mouse islet cells.
      Carbamazepine down-regulated the proapoptotic and endoplasmic reticulum stress
      signaling induced by cytokines. Together, these studies point to Na(+) channels
      as a novel therapeutic target in diabetes.

PMID- 24438340
TI  - Steroid receptor coactivator 1 is an integrator of glucose and NAD+/NADH
      homeostasis.
AB  - Steroid receptor coactivator 1 (SRC-1) drives diverse gene expression programs
      necessary for the dynamic regulation of cancer metastasis, inflammation and
      gluconeogenesis, pointing to its overlapping roles as an oncoprotein and
      integrator of cell metabolic programs. Nutrient utilization has been intensely
      studied with regard to cellular adaptation in both cancer and noncancerous cells.
      Nonproliferating cells consume glucose through the citric acid cycle to generate
      NADH to fuel ATP generation via mitochondrial oxidative phosphorylation. In
      contrast, cancer cells undergo metabolic reprogramming to support rapid
      proliferation. To generate lipids, nucleotides, and proteins necessary for cell
      division, most tumors switch from oxidative phosphorylation to glycolysis, a
      phenomenon known as the Warburg Effect. Because SRC-1 is a key coactivator
      responsible for driving a hepatic gluconeogenic program under fasting conditions,
      we asked whether SRC-1 responds to alterations in nutrient availability to allow
      for adaptive metabolism. Here we show SRC-1 is stabilized by the 26S proteasome
      in the absence of glucose. RNA profiling was used to examine the effects of SRC-1
      perturbation on gene expression in the absence or presence of glucose, revealing
      that SRC-1 affects the expression of complex I of the mitochondrial electron
      transport chain, a set of enzymes responsible for the conversion of NADH to
      NAD(+). NAD(+) and NADH were subsequently identified as metabolites that underlie
      SRC-1's response to glucose deprivation. Knockdown of SRC-1 in glycolytic cancer
      cells abrogated their ability to grow in the absence of glucose consistent with
      SRC-1's role in promoting cellular adaptation to reduced glucose availability. 

PMID- 24438342
TI  - Tailored support for type 2 diabetes patients with an acute coronary event after
      discharge from hospital - design and development of a randomised controlled
      trial.
AB  - BACKGROUND: Type 2 diabetes mellitus patients with an acute coronary event (ACE)
      experience decreased quality of life and increased distress. According to the
      American Diabetes Association, discharge from the hospital is a time of increased
      distress for all patients. Tailored support specific to diabetes is scarce in
      that period. We developed an intervention based on Bandura's Social Cognitive
      Theory, Leventhal's Common Sense Model, and results of focus groups. The aim of
      this study is to evaluate the effectiveness of the intervention to reduce
      distress in type 2 diabetes patients who experienced a first ACE. METHODS:
      Randomised controlled trial. Two hundred patients are recruited in thirteen
      hospitals. A diabetes nurse visits the patients in the intervention group (n =
      100) at home within three weeks after discharge from hospital, and again after
      two weeks and two months. The control group (n = 100) receives a consultation by
      telephone. The primary outcome is diabetes-related distress, measured with the
      Problem Areas in Diabetes (PAID) questionnaire. Secondary outcomes are well
      being, health status, anxiety, depression, HbA1c, blood pressure and lipids.
      Mediating variables are self-management, self-efficacy and illness
      representations. Outcomes are measured with questionnaires directly after
      discharge from hospital and five months later. Biomedical variables are obtained
      from the records from the primary care physician and the hospital. Differences
      between groups in change over time are analysed according to the intention-to
      treat principle. The Holm-Bonferroni correction is used to adjust for
      multiplicity. DISCUSSION: Type 2 diabetes patients who experience a first ACE
      need tailored support after discharge from the hospital. This trial will provide
      evidence on the effectiveness of a supportive intervention in reducing distress
      in these patients. TRIAL REGISTRATION: NCT01801631.

PMID- 24438344
TI  - African leaders' views on critical human resource issues for the implementation
      of family medicine in Africa.
AB  - BACKGROUND: The World Health Organisation has advocated for comprehensive primary
      care teams, which include family physicians. However, despite (or because of)
      severe doctor shortages in Africa, there is insufficient clarity on the role of
      the family physician in the primary health care team. Instead there is a trend
      towards task shifting without thought for teamwork, which runs the risk of
      dangerous oversimplification. It is not clear how African leaders understand the
      challenges of implementing family medicine, especially in human resource terms.
      This study, therefore, sought to explore the views of academic and government
      leaders on critical human resource issues for implementation of family medicine
      in Africa. METHOD: In this qualitative study, key academic and government leaders
      were purposively selected from sixteen African countries. In-depth interviews
      were conducted using an interview guide. All interviews were audio-recorded,
      transcribed and thematically analysed. RESULTS: There were 27 interviews
      conducted with 16 government and 11 academic leaders in nine Sub-Saharan African
      countries: Botswana, Democratic Republic of Congo, Ghana, Kenya, Malawi, Nigeria,
      Rwanda, South Africa and Uganda. Respondents spoke about: educating doctors in
      family medicine suited to Africa, including procedural skills and holistic care,
      to address the difficulty of recruiting and retaining doctors in rural and
      underserved areas; planning for primary health care teams, including family
      physicians; new supervisory models in primary health care; and general human
      resource management issues. CONCLUSIONS: Important milestones in African health
      care fail to specifically address the human resource issues of integrated primary
      health care teamwork that includes family physicians. Leaders interviewed in this
      study, however, proposed organising the district health system with a strong
      embrace of family medicine in Africa, especially with regard to providing
      clinical leadership in team-based primary health care. Whilst these leaders
      focussed positively on entry and workforce issues, in terms of the 2006 World
      Health Report on human resources for health, they did not substantially address
      retention of family physicians. Family physicians need to respond to the
      challenge by respondents to articulate human resource policies appropriate to
      Africa, including the organisational development of the primary health care team
      with more sophisticated skills and teamwork.

PMID- 24438343
TI  - Free radical scavenging and formation by multi-walled carbon nanotubes in cell
      free conditions and in human bronchial epithelial cells.
AB  - BACKGROUND: Certain multi-walled carbon nanotubes (MWCNTs) have been shown to
      elicit asbestos-like toxicological effects. To reduce needs for risk assessment
      it has been suggested that the physicochemical characteristics or reactivity of
      nanomaterials could be used to predict their hazard. Fibre-shape and ability to
      generate reactive oxygen species (ROS) are important indicators of high hazard
      materials. Asbestos is a known ROS generator, while MWCNTs may either produce or
      scavenge ROS. However, certain biomolecules, such as albumin - used as
      dispersants in nanomaterial preparation for toxicological testing in vivo and in
      vitro - may reduce the surface reactivity of nanomaterials. METHODS: Here, we
      investigated the effect of bovine serum albumin (BSA) and cell culture medium
      with and without BEAS 2B cells on radical formation/scavenging by five MWCNTs,
      Printex 90 carbon black, crocidolite asbestos, and glass wool, using electron
      spin resonance (ESR) spectroscopy and linked this to cytotoxic effects measured
      by trypan blue exclusion assay. In addition, the materials were characterized in
      the exposure medium (e.g. for hydrodynamic size-distribution and sedimentation
      rate). RESULTS: The test materials induced highly variable cytotoxic effects
      which could generally be related to the abundance and characteristics of
      agglomerates/aggregates and to the rate of sedimentation. All carbon
      nanomaterials were found to scavenge hydroxyl radicals (*OH) in at least one of
      the solutions tested. The effect of BSA was different among the materials. Two
      types of long, needle-like MWCNTs (average diameter >74 and 64.2 nm, average
      length 5.7 and 4.0 MUm, respectively) induced, in addition to a scavenging
      effect, a dose-dependent formation of a unique, yet unidentified radical in both
      absence and presence of cells, which also coincided with cytotoxicity.
      CONCLUSIONS: Culture medium and BSA affects scavenging/production of *OH by
      MWCNTs, Printex 90 carbon black, asbestos and glass-wool. An unidentified radical
      is generated by two long, needle-like MWCNTs and these two CNTs were more
      cytotoxic than the other CNTs tested, suggesting that this radical could be
      related to the adverse effects of MWCNTs.

PMID- 24438345
TI  - Screening for heat transport by groundwater in closed geothermal systems.
AB  - Heat transfer due to groundwater flow can significantly affect closed geothermal
      systems. Here, a screening method is developed, based on Peclet numbers for these
      systems and Darcy's law. Conduction-only conditions should not be expected where
      specific discharges exceed 10(-8)  m/s. Constraints on hydraulic gradients allow
      for preliminary screening for advection based on rock or soil types.
      Identification of materials with very low hydraulic conductivity, such as shale
      and intact igneous and metamorphic rock, allow for analysis with considering
      conduction only. Variability in known hydraulic conductivity allows for the
      possibility of advection in most other rocks and soil types. Further screening
      relies on refinement of estimates of hydraulic gradients and hydraulic
      conductivity through site investigations and modeling until the presence or
      absence of conduction can be confirmed. 

PMID- 24438346
TI  - Equine mesenchymal stem cells inhibit T cell proliferation through different
      mechanisms depending on tissue source.
AB  - Mesenchymal stem cells (MSCs) are used in both human clinical trials and
      veterinary medicine for the treatment of inflammatory and immune-mediated
      diseases. MSCs modulate inflammation by decreasing the cells and products of the
      inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose
      tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte
      proliferation and decrease inflammatory cytokine production. We hypothesized that
      equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs
      from different tissue sources decrease T cell proliferation through different
      mechanisms. To test our hypotheses, we inhibited interleukin-6 (IL-6), nitric
      oxide (NO), and prostaglandin E2 (PGE2) to determine their impact on stimulated T
      cell proliferation. We also determined how equine MSCs modulate lymphocyte
      proliferation either via cell cycle arrest or apoptosis. Inhibition of IL-6 or NO
      did not reverse the immunomodulatory effect of MSCs on activated T cells. In
      contrast, inhibition of PGE2 restored T cell proliferation, restored the
      secretion of tumor necrosis factor-alpha and interferon-gamma, and increased IL
      10 levels. MSCs from solid-tissue-derived sources, AT and CT, inhibited T cell
      proliferation through induction of lymphocyte apoptosis while blood-derived MSCs,
      BM and CB, induced lymphocyte cell cycle arrest. Equine MSCs from different
      tissue sources modulated immune cell function by both overlapping and unique
      mechanisms. MSC tissue source may determine immunomodulatory properties of MSCs
      and may have very practical implications for MSC selection in the application of
      MSC therapy. 

PMID- 24438347
TI  - Growth following solid organ transplantation in childhood.
AB  - One of the ultimate goals of successful transplantation in pediatric solid organ
      transplant recipients is the attainment of optimal final adult height. This
      manuscript will discuss the attainment of height following solid organ
      transplantation in pediatric recipients of kidney, liver, heart, lung, and small
      bowel transplantation. Age is a primary factor with younger recipients exhibiting
      the greatest immediate catch up growth. Graft function is a significant
      contributory factor with a reduction in glomerular filtration rate correlating
      with poor growth in kidney recipients and the need for re-transplantation with
      impaired growth in liver recipients. The known adverse impact of steroids on
      growth has led to modification of steroid dosage and even to steroid withdrawal
      and steroid avoidance. In kidney and liver recipients, this has been associated
      with the development on occasion of acute rejection episodes. In infant heart
      transplantation, avoidance of maintenance corticosteroid immunosuppression is
      associated with normal growth velocity in the majority of patients. With marked
      improvement in patient and graft survival rates in pediatric organ graft
      recipients, it is timely that the quality of life issues, such as normal adult
      height, receive paramount attention. In general, normal growth post
      transplantation should be an achievable goal that results in normal adult height
      for many solid organ transplantation recipients. 

PMID- 24438348
TI  - Metabolic syndrome in antipsychotic naive patients with schizophrenia: pooled
      analysis of data from three Indian studies.
AB  - AIM: This study aimed to assess the prevalence of metabolic syndrome (MS) and
      subthreshold MS in antipsychotic naive patients with schizophrenia by pooling the
      data from three different centres in India. METHODS: One hundred thirty-seven
      antipsychotic naive patients with schizophrenia were evaluated for MS using
      common criteria for clinical diagnosis. RESULTS: Twenty-six patients (19%) met
      consensus criteria. Additionally, 56 patients (40.9%) fulfilled one criterion and
      32 patients (23.3%) fulfilled two criteria of MS out of five criteria.
      CONCLUSION: One-fifth of antipsychotic naive patients with schizophrenia had MS
      and another two-third had at least one metabolic abnormality. Awareness of such a
      high risk is vitally important for rational selection of antipsychotic
      medications as well as effective implementation of preventive measures.

PMID- 24438349
TI  - Peroxisome proliferator-activated receptor activating hypoglycemic effect of
      Gardenia jasminoides Ellis aqueous extract and improvement of insulin sensitivity
      in steroid induced insulin resistant rats.
AB  - BACKGROUND: The active components of Gardenia (Gardenia jasminoides Ellis, GJ)
      exhibit a hypoglycemic effect by improving insulin secretion and lowering plasma
      lipids. In the present study, we fed a water extract of gardenia to steroid
      induced insulin-resistant (SIIR) rats and observed changes in signaling proteins
      in order to elucidate the mechanisms of the insulin-sensitizing effect of GJ and
      evaluate its possibility as an insulin-sensitizing agent. METHODS: Normal Wistar
      rats were randomly divided into a control group (i.e., saline) and experimental
      groups (GJ 100 and 200 mg/kg). Blood samples were taken at 0, 30, and 60 min for
      plasma glucose assay in order to determine the optimal dose to induce the
      hypoglycemic effect. SIIR rats were then randomly divided into a control group
      (i.e., saline) and an experimental group (optimal dose of gardenia extract) to
      observe the insulin-sensitizing effect of the extract. Finally, western blot
      analysis was performed to detect intracellular signaling proteins to elucidate
      the mechanisms of the insulin-sensitization effect of GJ. RESULTS: The normal
      Wistar rats in the GJ 200 mg/kg group exhibited significant hypoglycemic
      activity. Meanwhile, the SIIR rats had higher plasma glucose levels than normal
      rats. There was no obvious change in insulin level, but the insulin sensitivity
      index and homeostasis model assessment index were significantly elevated.
      Meanwhile, a significant hypoglycemic effect was observed with GJ 200 mg/kg. In
      addition, intracellular signaling proteins including insulin receptor substrate-1
      (IRS-1) and peroxisome proliferator-activated receptor (PPARgamma) were elevated
      in muscle cells. CONCLUSIONS: The optimal dose of GJ aqueous extract of 200 mg/kg
      exerts a PPARgamma-activating hypoglycemic effect and improves insulin resistance
      in SIIR rats. Therefore, it is a potential insulin-sensitizing agent in type 2
      diabetes mellitus with insulin resistance.

PMID- 24438350
TI  - Influence of differences in washing methods on skin texture.
AB  - OBJECTIVE: The objective of this study was to clarify the effects of different
      body washing methods on skin texture. METHODS: Subjects were nine healthy women
      in their 20s. Skin on the inside of the forearms was washed every day for 4 weeks
      with protective washing (right forearm) and with non-protective washing (left
      forearm). We performed comparison of the right forearm and the left forearm. For
      the evaluation of skin texture, the interval of the sulcus cutis, and the mean
      and variance of the thickness of the sulcus cutis on digitized images were
      measured. Moreover, the numbers of equilateral triangles consisting of sulcus
      cutis were counted to evaluate skin texture. RESULTS: From the first week, the
      interval of sulcus cutis was significantly narrower with protective washing than
      with non-protective washing. The numbers of equilateral triangles increased
      significantly more with protective washing than with non-protective washing in
      weeks 1, 2 and 4. Although this study found no significant difference in mean of
      the thickness of the sulcus cutis, the interval of sulcus cutis and the number of
      triangles differed significantly with protective washing. The narrower intervals
      between sulcus cutis mean finer-textured skin and sulcus cutis are formed by
      triangles or quadrilaterals, and the more uniform these shapes are, the finer and
      more regular the texture Therefore, skin texture may have become finer as a
      result of protective washing. CONCLUSION: These findings suggest that protective
      washing produces an even skin texture. They also suggest that number of
      equilateral triangles, as used in this study, may be useful as an index of skin
      texture.

PMID- 24438351
TI  - The importance of providing counselling and financial support to patients
      receiving treatment for multi-drug resistant TB: mixed method qualitative and
      pilot intervention studies.
AB  - BACKGROUND: People with multi-drug resistant tuberculosis (MDR-TB) in low-income
      countries face many problems during treatment, and cure rates are low. The
      purpose of the study was (a) to identify and document the problems experienced by
      people receiving care for MDR-TB, and how they cope when support is not provided,
      to inform development of strategies; (b) to estimate the effectiveness of two
      resultant strategies, counselling alone, and joint counselling and financial
      support, of increasing DOTS-plus treatment success under routine programme
      conditions. METHODS: A mixed-method study comprising a formative qualitative
      study, pilot intervention study and explanatory qualitative study to better
      understand barriers to completion of treatment for MDR-TB. Participants were all
      people starting MDR-TB treatment in seven DOTS-plus centres in the Kathmandu
      Valley, Nepal during January to December 2008. The primary outcome measure was
      cure, as internationally defined. RESULTS: MDR-TB treatment caused extreme
      social, financial and employment hardship. Most patients had to move house and
      leave their job, and reported major stigmatisation. They were concerned about the
      long-term effects of their disease, and feared infecting others. In the resultant
      pilot intervention study, the two strategies appeared to improve treatment
      outcomes: cure rates for those receiving counselling, combined support and no
      support were 85%, 76% and 67% respectively. Compared with no support, the
      (adjusted) risk ratios of cure for those receiving counselling and receiving
      combined support were 1.2 (95% CI 1.0 to 1.6) and 1.2 (95% CI 0.9 to 1.6)
      respectively. The explanatory study demonstrated that patients valued both forms
      of support. CONCLUSIONS: MDR-TB patients are extremely vulnerable to stigma and
      extreme financial hardship. Provision of counselling and financial support may
      not only reduce their vulnerability, but also increase cure rates. National
      Tuberculosis Programmes should consider incorporating financial support and
      counselling into MDR-TB care: costs are low, and benefits high, especially since
      costs to society of incomplete treatment and potential for incurable TB are
      extremely high.

PMID- 24438352
TI  - Immunology of relapse and remission in multiple sclerosis.
AB  - Eighty percent of individuals with multiple sclerosis (MS) initially develop a
      clinical pattern with periodic relapses followed by remissions, called relapsing
      remitting MS (RRMS). This period of fluctuating disease may last for a decade or
      more. Clinical relapses reflect acute inflammation in the central nervous system
      (CNS), composed of the brain and spinal cord. Often, different anatomic areas in
      the CNS are involved each time a relapse occurs, resulting in varied clinical
      manifestations in each instance. Relapses are nearly always followed by some
      degree of remission, though recovery to baseline status before the flare is often
      incomplete. There are nine approved drugs for treatment of RRMS. The most potent
      drug for inhibiting relapses, the humanized anti-alpha4 integrin antibody known
      as Natalizumab, blocks homing of mononuclear cells to the CNS. The mechanisms of
      action of the approved drugs for RRMS provide a strong foundation for
      understanding the pathobiology of the relapse. Despite substantial progress in
      controlling relapses with the current armamentarium of medications, there is much
      to learn and ever more effective and safe therapies to develop. 

PMID- 24438353
TI  - The role of surgery in the treatment of invasive fungal infection in paediatric
      haematology patients: a retrospective single-centre survey.
AB  - Surgery may improve the control of fungal disease and patient survival. The aim
      of this study was to report a single-centre experience in using surgery for the
      treatment of paediatric invasive fungal infection (IFI). From 2001 to 2009, 18
      paediatric onco-haematology patients underwent 24 surgical procedures as
      treatment of IFI. At surgery, severe thrombocytopenia and neutropenia were
      present in four and one episodes respectively. Complications were one pleural
      effusion, one pleural effusion and surgical wound infection, one pneumothorax
      with wound dehiscence and one wound dehiscence. None of them required repeat
      surgery. The median duration of hospitalisation for four complicated procedures
      was 11 days, range 3-16, and 7 days, range 2-13, for the 20 uncomplicated
      procedures. No surgery-related deaths occurred. Fourteen patients resumed
      chemotherapy after a median of 26 days, range 9-77, whereas nine patients
      underwent hematopoietic stem cell transplantation after a median of 42 days,
      range 27-110. At 3 months from IFI, 17 patients were alive (94%) and one patient
      (6%) died from mycosis; the 3-month overall survival (OS) being 94.4%, CI 66.6
      99.2. After a median follow-up of 7.1 years (CI 2.8-7.5), the OS was 54.5%, CI
      29.2-74.2. Surgery is a feasible and valuable option in paediatric patients
      because it is associated with a low incidence of complications and an acceptable
      delay in resuming the chemotherapeutic plan. 

PMID- 24438354
TI  - A novel HLA-B allele, HLA-B*44:184, identified by super high-resolution single
      molecule sequence-based typing in a Japanese individual.
AB  - The novel allele HLA-B*44:184 differs from HLA-B*44:77 by three non-synonymous
      amino acid exchanges, T94I, L95I and S97R. 

PMID- 24438355
TI  - Long-term outcomes from implants installed by using split-crest technique in
      posterior maxillae: 10 years of follow-up.
AB  - OBJECTIVE: The aim of the present 10-year retrospective study was to evaluate the
      success and survival rates of narrow diameter implants (NDIs) placed in
      combination with a split-crest technique. MATERIALS AND METHODS: Twenty-one
      healthy individuals who received prosthetic rehabilitation supported by narrow
      diameter implants (NDIs) installed in atrophic maxillary posterior areas
      immediately after split-crest procedure were included in the study. Six to eight
      weeks after implant placement, the prosthetic rehabilitations were delivered.
      Periapical radiographs were taken at the 6-month and 10-year time interval after
      implant loading to assess bone marginal level around the implants. In addition,
      survival and success indexes were also obtained at these time intervals. RESULTS:
      Forty NDIs were placed in 21 patients. At the end of the 10-year follow-up
      period, seven patients had dropped out, two implants were lost, and nine
      prostheses presented some type of deficiency (ceramic fracture or retaining screw
      fracture). At the 10-year time interval, the implant survival rate was 97% and
      the success rate was 95%. The marginal bone loss at the 6-month and 10-year time
      intervals was, respectively, 0.47 (SD 0.91) mm and 1.93 (SD 0.93) mm. CONCLUSION:
      Narrow diameter implants installed immediately after split-crest procedure may
      successfully support prosthetic rehabilitations after long-time intervals.

PMID- 24438356
TI  - The perfect storm? Histiocytoid cardiomyopathy and compound CACNA2D1 and RANGRF
      mutation in a baby.
AB  - A female baby suffered from a rare association between histiocytoid
      cardiomyopathy, left ventricular non-compaction, and Wolff-Parkinson-White
      syndrome causing severe and recurrent arrhythmic storms. Antiarrhythmic drugs,
      radiofrequency ablation of Purkinje tissue, and sympathetic denervation were
      ineffective. The implant of a cardiac defibrillator allowed her to survive till
      heart transplant. Compound mutation of CACNA2D1 and RANGRF genes were found. To
      the best of our knowledge, this is the first comprehensive description of the
      concurrence of these two mutations and histiocytoid cardiomyopathy. 

PMID- 24438357
TI  - Bidirectional promoters are the major source of gene activation-associated non
      coding RNAs in mammals.
AB  - BACKGROUND: The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism
      in mammals have been believed to downregulate the corresponding mRNA expression
      level in a pre- or post-transcriptional manner by forming short or long ncRNA
      mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also
      rapidly accumulating. To examine the directional properties of transcription at
      the whole-genome level, we performed directional RNA-seq analysis of mouse and
      chimpanzee tissue samples. RESULTS: We found that there is only about 1% of the
      genome where both the top and bottom strands are utilized for transcription,
      suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on
      transcription start sites (TSSs) of protein-coding genes revealed that a
      significant fraction of them contain switching-points that separate antisense-
      and sense-biased transcription, suggesting that head-to-head transcription is
      more prevalent than previously thought. More than 90% of head-to-head type
      promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly
      enriched in the upstream regions and downstream regions, respectively, of TSSs
      located in head-to-head type promoters. Genes with tissue-specific promoter
      associated ncRNAs (pancRNAs) show a positive correlation between the expression
      of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA
      in facultative gene activation, whereas genes with constitutive expression
      generally lack pancRNAs. CONCLUSIONS: We propose that single-stranded ncRNA
      resulting from head-to-head transcription at GC-rich sequences regulates tissue
      specific gene expression.

PMID- 24438358
TI  - The early diastolic myocardial velocity: a marker of increased risk in patients
      with coronary heart disease.
AB  - OBJECTIVE: Tissue Doppler imaging (TDI) is a promising echocardiographic modality
      allowing quantification of myocardial performance. However, the prognostic
      potential of TDI in patients with acute myocardial infarction (AMI) is not yet
      investigated. We sought to explore the ability of TDI in identifying patients at
      risk for new cardiovascular events after AMI. METHODS: One hundred and nineteen
      patients with AMI were recruited prospectively (mean age 61 years; range 32-81
      years of age). Patients with diabetes mellitus (DM) were excluded.
      Echocardiography was performed 3-12 months after AMI. Two-dimensional (2-D) and
      TDI variables were recorded. The patients were followed during a mean period of
      4.6 years (range 1-8 years). The primary end-point was defined as any of the
      following: death from any cause, non-fatal reinfarction or stroke, unstable
      angina pectoris, congestive heart failure requiring hospitalization and coronary
      revascularization procedure. RESULTS: Thirty patients had some form of
      cardiovascular events during follow-up. Seven patients had cardiovascular death,
      13 patients had reinfarction and four patients had a stroke. New angina or
      unstable angina was recorded in 21 patients. Of these patients, 13 underwent
      percutaneous coronary angioplasty (PCI) or coronary artery bypass grafting
      (CABG). The early diastolic myocardial velocity (E(m)) emerged as the only
      echocardiographic variable that offered a clear differentiation between patients
      that presented with new cardiovascular (CV) events as compared to the
      corresponding group without any CV events at follow-up (P<0.05). In multivariate
      statistical analysis and after adjustment for age, sex, total cholesterol, body
      mass index (BMI) and other baseline characteristics, Em remained as independent
      predictors of CV events (HR, 1.18, 95% CI, 1.02-1.36; P<0.05). However, none of
      the investigated variables evolved as an independent predictor of cardiovascular
      morbidity and mortality. CONCLUSION: E(m) appears to be a sensitive
      echocardiographic index in identifying non-diabetic patients with AMI at risk of
      new cardiovascular events.

PMID- 24438359
TI  - Multimodal keloid therapy with excision, application of mitomycin C, and
      radiotherapy.

PMID- 24438361
TI  - Do home visiting services received during pregnancy improve birth outcomes?
      Findings from Virginia PRAMS 2007-2008.
AB  - OBJECTIVES: Reducing poor birth outcomes are national and state priorities. At
      the national level participation in home visiting services has gained momentum
      with the recent appropriation of federal funds for states to implement evidence
      based maternal and child health home visiting programs. The effects of having a
      home visit are unknown at the state level. DESIGN AND SAMPLE: Using cross
      sectional data from 2007 to 2008 Virginia Pregnancy Risk Assessment and
      Monitoring System (PRAMS), maternal and infant outcomes were examined. Women who
      had a home visit during pregnancy were assigned into the home visiting (HV)
      participation group and those who did not were assigned to the HV Comparison
      group and used for the analysis. MEASURES: Bivariate analyses, Rao-Scott chi
      square tests, and multivariate logistic regression measured and quantified the
      association between HV participation and outcomes. RESULTS: The HV Participation
      group were 87.5% less likely to have a low birth weight infant (0.13, 95% CI:
      0.020, 0.78), 4.5 times more likely to initiate breastfeeding (aOR: 4.5, 95% CI:
      1.05, 19.54), and 39 times more likely to use contraceptives postpartum (aOR:
      38.55, 95% CI: 3.14, 473.21). CONCLUSIONS: Receiving home visiting services
      during pregnancy increased breastfeeding initiation and postpartum contraceptive
      use while reducing the risk of low birth weight.

PMID- 24438360
TI  - Citrate confers less filter-induced complement activation and neutrophil
      degranulation than heparin when used for anticoagulation during continuous
      venovenous haemofiltration in critically ill patients.
AB  - BACKGROUND: During continuous venovenous haemofiltration (CVVH), regional
      anticoagulation with citrate may be superior to heparin in terms of
      biocompatibility, since heparin as opposed to citrate may activate complement
      (reflected by circulating C5a) and induce neutrophil degranulation in the filter
      and myeloperoxidase (MPO) release from endothelium. METHODS: No anticoagulation
      (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens
      during CVVH were compared. Blood samples were collected pre- and postfilter; C5a,
      elastase and MPO were determined by ELISA. Additionally, C5a was also measured in
      the ultrafiltrate. RESULTS: In the heparin group, there was C5a production across
      the filter which most decreased over time as compared to other groups (P =
      0.007). There was also net production of elastase and MPO across the filter
      during heparin anticoagulation (P = 0.049 or lower), while production was minimal
      and absent in the no anticoagulation and citrate group, respectively. During
      heparin anticoagulation, plasma concentrations of MPO at the inlet increased in
      the first 10 minutes of CVVH (P = 0.024). CONCLUSION: Citrate confers less filter
      induced, potentially harmful complement activation and neutrophil degranulation
      and less endothelial activation than heparin when used for anticoagulation during
      continuous venovenous haemofiltration in critically ill patients.

PMID- 24438362
TI  - Detecting concept mentions in biomedical text using hidden Markov model: multiple
      concept types at once or one at a time?
AB  - BACKGROUND: Identifying phrases that refer to particular concept types is a
      critical step in extracting information from documents. Provided with annotated
      documents as training data, supervised machine learning can automate this
      process. When building a machine learning model for this task, the model may be
      built to detect all types simultaneously (all-types-at-once) or it may be built
      for one or a few selected types at a time (one-type- or a-few-types-at-a-time).
      It is of interest to investigate which strategy yields better detection
      performance. RESULTS: Hidden Markov models using the different strategies were
      evaluated on a clinical corpus annotated with three concept types (i2b2/VA
      corpus) and a biology literature corpus annotated with five concept types (JNLPBA
      corpus). Ten-fold cross-validation tests were conducted and the experimental
      results showed that models trained for multiple concept types consistently
      yielded better performance than those trained for a single concept type. F-scores
      observed for the former strategies were higher than those observed for the latter
      by 0.9 to 2.6% on the i2b2/VA corpus and 1.4 to 10.1% on the JNLPBA corpus,
      depending on the target concept types. Improved boundary detection and reduced
      type confusion were observed for the all-types-at-once strategy. CONCLUSIONS: The
      current results suggest that detection of concept phrases could be improved by
      simultaneously tackling multiple concept types. This also suggests that we should
      annotate multiple concept types in developing a new corpus for machine learning
      models. Further investigation is expected to gain insights in the underlying
      mechanism to achieve good performance when multiple concept types are considered.

PMID- 24438363
TI  - Species and sex-dependent toxicokinetics of 1-bromopropane: the role of hepatic
      cytochrome P450 oxidation and glutathione (GSH).
AB  - 1. The objectives of the current studies were to evaluate the factors influencing
      the toxicokinetics of 1-bromopropane (1-BP) in rodents after intravenous (IV) and
      inhalation exposure. 2. F-344 rats were administered 1-BP via IV bolus injection
      at 5 and 20 mg/kg and blood concentration determined versus time. F-344 rats and
      B6C3F1 mice were also exposed to starting inhalation concentrations 70, 240, 800
      and 2700 ppm 1-BP in a closed gas uptake system and chamber 1-BP levels were
      monitored for 6 h. Plasma bromide concentrations were determined to estimate
      total metabolized dose. Rats were pretreated with chemical inhibitors of
      cytochrome P450 and glutathione (GSH) synthesis, prior to exposure to 1-BP at 800
      ppm within inhalation chambers. 3. Systemic clearance of 1-BP in rat was rapid
      and decreased with increasing dose. As inhalation chamber concentration of 1-BP
      increased, the terminal elimination rates decreased. Half-life of 1-BP in rats
      following inhibition of P450 (9.6 h) or depletion of GSH (4.1 h) increased
      relative to controls (2.0 h) at 800 ppm. The percentage of 1-BP metabolized
      decreased with increasing inhalation exposure. Hepatic levels of GSH were
      significantly lowered regardless of the exposure level in both rats and mice.
      Chamber concentration-time curves were fit to a two compartment model which was
      used to estimate metabolic rate constants. 4. These data suggest that in rat, 1
      BP clearance is saturable and that elimination is highly dependent on both P450
      and GSH-dependent metabolism. This investigation in rodents may provide an
      understanding of interspecies differences in toxicokinetics and eventually aid
      translation of animal studies to human risk assessment.

PMID- 24438364
TI  - Protein interaction networks as metric spaces: a novel perspective on
      distribution of hubs.
AB  - BACKGROUND: In the post-genomic era, a central and overarching question in the
      analysis of protein-protein interaction networks continues to be whether
      biological characteristics and functions of proteins such as lethality,
      physiological malfunctions and malignancy are intimately linked to the
      topological role proteins play in the network as a mathematical structure. One of
      the key features that have implicitly been presumed is the existence of hubs,
      highly connected proteins considered to play a crucial role in biological
      networks. We explore the structure of protein interaction networks of a number of
      organisms as metric spaces and show that hubs are non randomly positioned and,
      from a distance point of view, centrally located. RESULTS: By analysing how the
      human functional protein interaction network, the human signalling network,
      Saccharomyces cerevisiae, Arabidopsis thaliana and Escherichia coli protein
      protein interaction networks from various databases are distributed as metric
      spaces, we found that proteins interact radially through a central node, high
      degree proteins coagulate in the centre of the network, and those far away from
      the centre have low degree. We further found that the distribution of proteins
      from the centre is in some hierarchy of importance and has biological
      significance. CONCLUSIONS: We conclude that structurally, protein interaction
      networks are mathematical entities that share properties between organisms but
      not necessarily with other networks that follow power-law. We therefore conclude
      that (i) if there are hubs defined by degree, they are not distributed randomly;
      (ii) zones closest to the centre of the network are enriched for critically
      important proteins and are also functionally very specialised for specific 'house
      keeping' functions; (iii) proteins closest to the network centre are functionally
      less dispensable and may present good targets for therapy development; and (iv)
      network biology requires its own network theory modelled on actual biological
      evidence and that simply adopting theories from the social sciences may be
      misleading.

PMID- 24438365
TI  - Capturing lessons learned from evidence-to-policy initiatives through structured
      reflection.
AB  - BACKGROUND: Knowledge translation platforms (KTPs), which are partnerships
      between policymakers, stakeholders, and researchers, are being established in low
      and middle-income countries (LMICs) to enhance evidence-informed health
      policymaking (EIHP). This study aims to gain a better understanding of the i)
      activities conducted by KTPs, ii) the way in which KTP leaders, policymakers, and
      stakeholders perceive these activities and their outputs, iii) facilitators that
      support KTP work and challenges, and the lessons learned for overcoming such
      challenges, and iv) factors that can help to ensure the sustainability of KTPs.
      METHODS: This paper triangulated qualitative data from: i) 17 semi-structured
      interviews with 47 key informants including KTP leaders, policymakers, and
      stakeholders from 10 KTPs; ii) document reviews, and iii) observation of
      deliberations at the International Forum on EIHP in LMICs held in Addis Ababa in
      August 2012. Purposive sampling was used and data were analyzed using thematic
      analysis. RESULTS: Deliberative dialogues informed by evidence briefs were
      identified as the most commendable tools by interviewees for enhancing EIHP. KTPs
      reported that they have contributed to increased awareness of the importance of
      EIHP and strengthened relationships among policymakers, stakeholders, and
      researchers. Support from policymakers and international funders facilitated KTP
      activities, while the lack of skilled human resources to conduct EIHP activities
      impeded KTPs. Ensuring the sustainability of EIHP initiatives after the end of
      funding was a major challenge for KTPs. KTPs reported that institutionalization
      within the government has helped to retain human resources and secure funding,
      whereas KTPs hosted by universities highlighted the advantage of autonomy from
      political interests. CONCLUSIONS: The establishment of KTPs is a promising
      development in supporting EIHP. Real-time lesson drawing from the experiences of
      KTPs can support improvements in the functioning of KTPs in the short term, while
      making the case for sustaining their work in the long term. Lessons learned can
      help to promote similar EIHP initiatives in other countries.

PMID- 24438366
TI  - Clinical relevance of positive human parechovirus type 1 and 3 PCR in stool
      samples.
AB  - Human parechoviruses (HPeV) cause symptoms ranging from severe neonatal
      infections to mild gastrointestinal and respiratory disease. Use of PCR and
      genotyping has markedly improved the detection rate of HPeV but has
      simultaneously raised questions about the clinical relevance of positive tests.
      This retrospective study correlates positive HPeV1 or HPeV3 PCR tests in stools
      from children with their symptoms to determine clinical relevance. Children with
      HPeV1- or HPeV3-positive stool samples, as detected by real time RT-PCR and
      direct genotyping, between 2004 and 2008 were selected. Clinical data were
      retrospectively collected from the patient's files and results were compared. One
      hundred and thirty-eight children with positive HPeV1 (n = 112) or HPeV3 (n = 26)
      stool samples were identified. Significantly more HPeV3-infected children were
      neonates or infants younger than 6 months of age. Meningitis or sepsis-like
      illnesses were diagnosed most frequently and were found in significantly younger
      children. Almost half of HPeV1-infected children had an underlying disease. Mild
      gastrointestinal disease was seen most frequently in these children. There was no
      clear correlation between viral load (Ct value) and severity of symptoms. In
      conclusion, HPeV3 detected by PCR in stool samples is associated with clinically
      relevant disease. For HPeV1, a positive stool sample is mainly associated with
      symptoms in children with underlying disease.

PMID- 24438367
TI  - B-type natriuretic peptide is neither itch-specific nor functions upstream of the
      GRP-GRPR signaling pathway.
AB  - BACKGROUND: A recent study by Mishra and Hoon identified B-type natriuretic
      peptide (BNP) as an important peptide for itch transmission and proposed that BNP
      activates spinal natriuretic peptide receptor-A (NPRA) expressing neurons, which
      release gastrin releasing peptide (GRP) to activate GRP receptor (GRPR)
      expressing neurons to relay itch information from the periphery to the brain
      (Science 340:968-971, 2013). A central premise for the validity of this novel
      pathway is the absence of GRP in the dorsal root ganglion (DRG) neurons. To this
      end, they showed that Grp mRNA in DRG neurons is either absent or barely
      detectable and claimed that BNP but not GRP is a major neurotransmitter for itch
      in pruriceptors. They showed that NPRA immunostaining is perfectly co-localized
      with Grp-eGFP in the spinal cord, and a few acute pain behaviors in Nppb-/- mice
      were tested. They claimed that BNP is an itch-selective peptide that acts as the
      first station of a dedicated neuronal pathway comprising a GRP-GRPR cascade for
      itch. However, our studies, along with the others, do not support their claims.
      FINDINGS: We were unable to reproduce the immunostaining of BNP and NPRA as shown
      by Mishra and Hoon. By contrast, we were able to detect Grp mRNA in DRGs using in
      situ hybridization and real time RT-PCR. We show that the expression pattern of
      Grp mRNA is comparable to that of GRP protein in DRGs. Pharmacological and
      genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal
      BNP-induced scratching behavior. We show that BNP inhibits inflammatory pain and
      morphine analgesia. CONCLUSIONS: Accumulating evidence demonstrates that GRP is a
      key neurotransmitter in pruriceptors for mediating histamine-independent itch.
      BNP-NPRA signaling is involved in both itch and pain and does not function
      upstream of the GRP-GRPR dedicated neuronal pathway. The site of BNP action in
      itch and pain and its relationship with GRP remain to be clarified.

PMID- 24438368
TI  - Anatomy of the lamprey ear: morphological evidence for occurrence of horizontal
      semicircular ducts in the labyrinth of Petromyzon marinus.
AB  - In jawed (gnathostome) vertebrates, the inner ears have three semicircular canals
      arranged orthogonally in the three Cartesian planes: one horizontal (lateral) and
      two vertical canals. They function as detectors for angular acceleration in their
      respective planes. Living jawless craniates, cyclostomes (hagfish and lamprey)
      and their fossil records seemingly lack a lateral horizontal canal. The jawless
      vertebrate hagfish inner ear is described as a torus or doughnut, having one
      vertical canal, and the jawless vertebrate lamprey having two. These observations
      on the anatomy of the cyclostome (jawless vertebrate) inner ear have been
      unchallenged for over a century, and the question of how these jawless
      vertebrates perceive angular acceleration in the yaw (horizontal) planes has
      remained open. To provide an answer to this open question we reevaluated the
      anatomy of the inner ear in the lamprey, using stereoscopic dissection and
      scanning electron microscopy. The present study reveals a novel observation: the
      lamprey has two horizontal semicircular ducts in each labyrinth. Furthermore, the
      horizontal ducts in the lamprey, in contrast to those of jawed vertebrates, are
      located on the medial surface in the labyrinth rather than on the lateral
      surface. Our data on the lamprey horizontal duct suggest that the appearance of
      the horizontal canal characteristic of gnathostomes (lateral) and lampreys
      (medial) are mutually exclusive and indicate a parallel evolution of both
      systems, one in cyclostomes and one in gnathostome ancestors. 

PMID- 24438369
TI  - Allopurinol enhanced thiopurine treatment for inflammatory bowel disease: safety
      considerations and guidelines for use.
AB  - WHAT IS KNOWN AND OBJECTIVE: The thiopurine medications are standard inflammatory
      bowel disease treatments. Therapeutic failure is observed, however, often because
      of variable drug metabolism. Allopurinol can enhance the potency of thiopurine
      treatment. Our objective is to review the relevant literature, and our own
      experience, to determine if allopurinol enhancement of thiopurine treatment is a
      reasonable therapeutic strategy. COMMENT: Published reports of, and our own
      experience using, allopurinol-thiopurine combination therapy indicate that the
      addition of allopurinol will enhance thiopurine treatment in up to 60% of
      patients. There are risks to this approach, but with appropriate monitoring,
      these risks should approximate those observed with thiopurine therapy alone. WHAT
      IS NEW AND CONCLUSION: Combination therapy with allopurinol and a thiopurine is a
      reasonable alternative for inflammatory bowel disease patients not responding to
      thiopurine monotherapy. Physicians experienced in thiopurine treatment, who have
      familiarity with thiopurine metabolism, and are willing to engage in appropriate
      therapeutic monitoring, should consider this strategy.

PMID- 24438370
TI  - Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a
      randomized trial.
AB  - OBJECTIVE: This phase 3 study evaluated the endometrial safety of bazedoxifene
      (BZA)/conjugated estrogens (CE) and bone mineral density (BMD) effects vs BZA
      alone, hormone therapy, and placebo (PBO). METHODS: The Selective estrogens,
      Menopause, And Response to Therapy (SMART)-5 trial was a multicenter, randomized,
      double-blind, PBO- and active-controlled study in postmenopausal women with an
      intact uterus (N = 1843; aged 40-65 years) seeking treatment for menopausal
      symptoms. Subjects received daily oral BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg,
      CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO. Primary endpoints
      were incidence of endometrial hyperplasia and percent change in lumbar spine BMD
      at 12 months. Secondary endpoints included additional osteoporosis parameters and
      assessments of tolerability and safety. RESULTS: At 12 months, endometrial
      hyperplasia incidence was low (<1%) and similar among groups. The BZA/CE group
      showed significantly greater increases in lumbar spine and total hip BMD vs
      decreases with PBO (P < .001); the CE/MPA group had increased lumbar spine BMD
      compared with that in the BZA/CE group. The BZA 20 mg/CE 0.45 and 0.625 mg groups
      had cumulative amenorrhea rates similar to those with PBO and BZA and
      significantly higher than those with CE 0.45 mg/MPA 1.5 mg (P < .001). The
      incidence of breast tenderness with BZA/CE was similar to that with PBO and BZA
      and significantly lower than with that with CE/MPA (P < .01). Although adverse
      event (AE) rates were similar among the groups, the incidence of serious AEs
      overall and AE-related discontinuation rates were higher with CE/MPA than with
      BZA/CE, BZA, or PBO. CONCLUSIONS: BZA/CE showed low rates of endometrial
      hyperplasia and improved lumbar spine and total hip BMD and was generally safe
      and well tolerated.

PMID- 24438371
TI  - Obestatin levels are associated with C-peptide and antiinsulin antibodies at the
      onset, whereas unacylated and acylated ghrelin levels are not predictive of long
      term metabolic control in children with type 1 diabetes.
AB  - CONTEXT AND OBJECTIVE: Ghrelin secretion is altered at the onset and after the
      start of insulin therapy in children with type 1 diabetes. Contemporary
      regulation of acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin
      (OBST) remains undefined in this disease. It is unknown as to whether they could
      be good predictors of changes in glucose and metabolic control. DESIGN, SETTING,
      AND SUBJECTS: This was a longitudinal study conducted in a tertiary care center.
      AG, UAG, and OBST were measured at baseline and after 2 years of follow-up in 51
      children and adolescents with a history of type 1 diabetes extending beyond 1
      year. A total of 33 healthy matched subjects were used as controls. RESULTS: Age
      , puberty-, and body mass index-adjusted UAG levels were lower (P < .005) and
      OBST levels were higher (P < .009) in children with type 1 diabetes, with respect
      to controls. AG levels were similar to controls, but all ratios of the three
      peptides are altered in diabetic patients. OBST (P < .05) was negatively
      correlated with C-peptide (P < .05) and insulin antibodies (P < .008) at the
      onset of diabetes. In diabetic patients, baseline AG and UAG levels were
      negatively correlated with insulin dosage in the short and long term (P < .001).
      AG, but not OBST, was positively correlated with C-peptide levels 2 years after
      diagnosis (P < .05). Overall, the peptides were not predictive of glucose and
      metabolic control. CONCLUSIONS: UAG, AG, OBST, and their ratios are differently
      regulated in children with type 1 diabetes, suggesting a role in the metabolic
      balance of the disease, with insulin a likely regulator of AG and UAG. The
      peptides do not appear to be good long-term predictors of glucose control, with
      further investigations needed to explain whether OBST could be a precocious
      predictor of islet dysfunction.

PMID- 24438372
TI  - Assessing the impact of growth hormone deficiency and treatment in adults:
      development of a new disease-specific measure.
AB  - CONTEXT: Approximately 50 000 adults in the United States are diagnosed with GH
      deficiency, which has negative impacts on cognitive functioning, psychological
      well-being, and quality of life. OBJECTIVE: This paper presents development and
      validation of a patient-reported outcome measure (PRO), the Treatment-Related
      Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD). The TRIM-AGHD was
      developed to measure the impact of GH deficiency and its treatment. DESIGN AND
      SETTINGS: The development and validation of the TRIM-AGHD was conducted according
      to the Food and Drug Administration guidance on the development of PROs. Concept
      elicitation, conducted in three countries included interviews with patients,
      clinical experts, and literature review. Qualitative data were analyzed based on
      grounded theory principles, and draft items were cognitively debriefed. The
      measure underwent psychometric validation in a US clinic-based population. An a
      priori statistical analysis plan included assessment of the measurement model,
      reliability, and validity. Item functioning was reviewed using item response
      theory analyses. PATIENTS OR OTHER PARTICIPANTS: Forty-eight patients and six
      clinical experts participated in concept elicitation and 169 patients completed
      the validation study. MAIN OUTCOME MEASURE: TRIM-AGHD was measured. RESULTS:
      Factor analysis resulted in four domains: energy level, physical health,
      emotional health, and cognitive ability. The item response theory confirmed
      adequate item fit and placement within their domain. Internal consistency ranged
      from 0.82 to 0.95 and test-retest ranged from 0.80 to 0.92. All prespecified
      hypotheses for convergent validity and all but two for discriminant validity were
      met. CONCLUSIONS: The final 26-item TRIM-AGHD can be considered a reliable and
      valid PRO of the impact of disease and treatment for adult GH deficiency.

PMID- 24438373
TI  - Anti-Mullerian hormone deficiency in females with Fanconi anemia.
AB  - CONTEXT: In females with Fanconi anemia (FA), infertility is often accompanied by
      diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30
      years, suggesting primary ovarian insufficiency (POI). POI is typically diagnosed
      only after perimenopausal symptoms are observed. OBJECTIVE: The objective of the
      study was to assess whether serum anti-Mullerian hormone (AMH) levels can serve
      as a cycle-independent marker for the diagnosis of POI in patients with FA.
      DESIGN AND SETTING: This observational study used the National Cancer Institute's
      inherited bone marrow failure syndrome cohort at the National Institutes of
      Health Clinical Center. PARTICIPANTS: The study included 22 females with FA, 20
      unaffected female relatives of patients with FA, and 21 unrelated healthy females
      under 41 years of age. MAIN OUTCOME MEASURE: Serum AMH, a marker of ovarian
      reserve, was measured in all participants. RESULTS: Females with FA had very low
      AMH levels (median 0.05 ng/mL; range 0-2.32 ng/mL; P < .001) when compared with
      unaffected relatives (median 2.10 ng/mL; range 0.04-4.73 ng/mL) and unrelated
      healthy females (median 1.92 ng/mL; range 0.31-6.64 ng/mL). All patients with FA
      older than 25 years of age were diagnosed with POI and had undetectable AMH
      levels. CONCLUSIONS: AMH deficiency appears to be a shared trait across this
      heterogeneous FA cohort. Substantially reduced AMH levels in females with FA
      suggest a primary ovarian defect associated with reduced fertility. Measurement
      of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at
      regular intervals may be useful for the timely management of complications
      related to POI such as subfertility/infertility, osteoporosis, and menopausal
      symptoms.

PMID- 24438374
TI  - Autosomal dominant pseudohypoparathyroidism type Ib: a novel inherited deletion
      ablating STX16 causes loss of imprinting at the A/B DMR.
AB  - CONTEXT: Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare imprinting disorder
      characterized by end-organ resistance to PTH and, frequently, to thyroid
      stimulating hormone. PHP-Ib familial form, with an autosomal dominant pattern of
      transmission (autosomal dominant pseudohypoparathyroidism type Ib [AD-PHP-Ib]),
      is typically characterized by an isolated loss of methylation at the guanine
      nucleotide-binding protein alpha-stimulating activity polypeptide 1 A/B
      differentially methylated region (DMR), secondary to genetic deletions disrupting
      the upstream imprinting control region in the syntaxin-16 (STX16) locus. However,
      deletions described up to now failed to account some cases of patients with a
      methylation defect limited to the A/B DMR; thus, it is expected the existence of
      other still unknown rearrangements, undetectable with conventional molecular
      diagnostic methods. OBJECTIVE: We investigated a PHP-Ib patient with a
      methylation defect limited to the A/B DMR and no known STX16 deletions to find
      the underlying primary genetic defect. PATIENT AND METHODS: A PHP-Ib patient
      (hypocalcaemia, hyperphosphataemia, raised serum PTH levels, no vitamin D
      deficiency) and his unaffected relatives were investigated by methylation
      specific-multiplex ligand-dependent probe amplification to search for novel
      pathogenetic defects affecting the guanine nucleotide-binding protein alpha
      stimulating activity polypeptide 1 and STX16 loci. RESULTS: We report the
      clinical, biochemical, and molecular analysis of an AD-PHP-Ib patient with a
      novel STX16 deletion overlapping with previously identified STX16 deletions but
      that, unlike these genetic defects associated with AD-PHP-Ib, goes unnoticed with
      commonly used first-level diagnostic techniques. CONCLUSIONS: Our work highlights
      the importance of performing accurate investigations in PHP-Ib patients with
      methylation defects to allow precise genetic counseling because, in case of
      deletions, the segregation ratio is about 50% and the disease phenotype is
      transmitted in an autosomal dominant fashion via the mother.

PMID- 24438375
TI  - Aberrant GDF9 expression and activation are associated with common human ovarian
      disorders.
AB  - CONTEXT: Growth differentiation factor 9 (GDF9) is a central regulator of
      folliculogenesis and ovulation rate. Fourteen mutations in human (h) GDF9 have
      been reported in women with premature ovarian failure or polycystic ovarian
      syndrome as well as in mothers of dizygotic twins, implicating GDF9 in the
      etiology of these conditions. We sought to determine how these mutations alter
      the biological activity of hGDF9. OBJECTIVE: The objective of the study was to
      determine whether aberrant GDF9 expression or activation is associated with
      common ovarian disorders. DESIGN: Homology modeling was used to predict the
      location of individual mutations within structurally important regions of the pro
      domains and mature domains of hGDF9. Each hGDF9 variant was generated by site
      directed mutagenesis, expressed from human embryonic kidney 293T cells and
      assessed as to whether it resulted in defective production or the enhanced
      activation of mature hGDF9 in an in vitro granulosa cell proliferation bioassay.
      RESULTS: Mutations observed in mothers of dizygotic twins (P103S and P374L)
      completely abrogated GDF9 expression, suggesting that women heterozygous for
      these mutations would have a 50% reduction in GDF9 levels. Comparable declines in
      GDF9 in ewes result in a 2-fold increase in ovulation rate and fecundity.
      Remarkably, three prodomain mutations associated with premature ovarian failure
      (S186Y, V216M, and T238A) all resulted in the activation of hGDF9.
      Mechanistically, these mutations reduced the affinity of the prodomain for mature
      hGDF9, allowing the growth factor to more readily access its signaling receptors.
      CONCLUSIONS: Together these findings indicate that alterations to hGDF9 synthesis
      and activity can contribute to the most common ovarian pathologies.

PMID- 24438376
TI  - Skeletal muscle mitochondria in the elderly: effects of physical fitness and
      exercise training.
AB  - CONTEXT: Sarcopenia is thought to be associated with mitochondrial (Mito) loss.
      It is unclear whether the decrease in Mito content is consequent to aging per se
      or to decreased physical activity. OBJECTIVES: The objective of the study was to
      examine the influence of fitness on Mito content and function and to assess
      whether exercise could improve Mito function in older adults. DESIGN AND
      SUBJECTS: Three distinct studies were conducted: 1) a cross-sectional observation
      comparing Mito content and fitness in a large heterogeneous cohort of older
      adults; 2) a case-control study comparing chronically endurance-trained older
      adults and sedentary (S) subjects matched for age and gender; and 3) a 4-month
      exercise intervention in S. SETTING: The study was conducted at a university
      based clinical research center. OUTCOMES: Mito volume density (MitoVd) was
      assessed by electron microscopy from vastus lateralis biopsies, electron
      transport chain proteins by Western blotting, mRNAs for transcription factors
      involved in M biogenesis by quantitative RT-PCR, and in vivo oxidative capacity
      (ATPmax) by (31)P-magnetice resonance spectroscopy. Peak oxygen uptake was
      measured by graded exercise test. RESULTS: Peak oxygen uptake was strongly
      correlated with MitoVd in 80 60- to 80-year-old adults. Comparison of chronically
      endurance-trained older adults vs S revealed differences in MitoVd, ATPmax, and
      some electron transport chain protein complexes. Finally, exercise intervention
      confirmed that S subjects are able to recover MitoVd, ATPmax, and specific
      transcription factors. CONCLUSIONS: These data suggest the following: 1) aging
      per se is not the primary culprit leading to Mito dysfunction; 2) an aerobic
      exercise program, even at an older age, can ameliorate the loss in skeletal
      muscle Mito content and may prevent aging muscle comorbidities; and 3) the
      improvement of Mito function is all about content.

PMID- 24438377
TI  - Central precocious puberty in a girl and early puberty in her brother caused by a
      novel mutation in the MKRN3 gene.
AB  - CONTEXT: Central precocious puberty (CPP), defined as the development of
      secondary sex characteristics prior to age 8 years in girls and 9 years in boys,
      results from the premature activation of the hypothalamic-pituitary-gonadal axis.
      Mutations in the imprinted gene MKRN3 have been recently implicated in familial
      cases of CPP. OBJECTIVE: The objective of the study was to uncover the genetic
      cause of CPP in a family with two affected siblings. DESIGN AND PARTICIPANTS: The
      entire coding region of the paternally expressed MKRN3 gene was sequenced in two
      siblings, a girl with CPP and her brother with early puberty, their parents, and
      their grandparents. RESULTS: A novel heterozygous missense variant in the MKRN3
      gene (p.C340G) was detected in the two affected siblings, their unaffected
      father, and the paternal grandmother. As expected, the mutated allele followed an
      imprinted mode of inheritance within the affected family. In silico analysis
      predicts the mutation as possibly damaging in all five software packages used.
      Furthermore, structural alignment of the ab initio native and mutant MKRN3 models
      predicts that the p.C340G mutation leads to significant structural perturbations
      in the 3-dimensional structure of the C3HC4 really interesting new gene motif of
      the protein, further emphasizing the functional implications of the novel MKRN3
      alteration. CONCLUSIONS: We report a novel MKRN3 mutation (p.C340G) in a girl
      with CPP and her brother with early puberty. MKRN3 alterations should be
      suspected in all cases with familial CPP or early puberty, especially if male
      patients are also involved or the precocious puberty trend does not follow the
      usually observed mother-to-daughter inheritance.

PMID- 24438378
TI  - The use of NGAL and IP-10 in the prediction of early acute rejection in highly
      sensitized patients following HLA-incompatible renal transplantation.
AB  - Acute rejection is a significant problem for patients undergoing HLA-incompatible
      renal transplantation, affecting between 12 and 53% of patients. Any mechanism of
      detecting rejection in advance of current methods would offer significant
      benefit. This study aimed to evaluate whether serum biomarkers could predict
      rejection in HLAi transplants recipients. Sera from 94 HLAi transplant recipients
      from a single centre were analysed for a panel of biomarkers including: NGAL, KIM
      1, IP-10, cystatin C, cathepsin L and VEGF. Biomarker levels pre-operatively, day
      1 and at day 30 post-transplant were correlated with the development of early
      rejection. Significantly higher levels of IP-10 and NGAL were seen on day 1
      following transplant in those patients who developed acute rejection (P < 0.001
      and 0.005) and generated AUC of 0.73 and 0.67, respectively. No differences were
      seen for the other biomarkers or at the other time points. In this study cohort,
      IP-10 and NGAL have demonstrated good predictive ability for the development of
      acute rejection at a very early time point. They may have a role in identifying
      patients at higher risk for rejection and stratifying immunosuppression or
      surveillance.

PMID- 24438379
TI  - Identification of a novel HLA-C*04 allele, HLA-C*04:162.
AB  - HLA-C*04:162 differs from the closely matching allele C*04:01:01:01 by one
      nucleotide substitution in exon 4 at position 883 A/G. 

PMID- 24438380
TI  - Anti-hyperglycemic activity of Centella asiatica is partly mediated by
      carbohydrase inhibition and glucose-fiber binding.
AB  - BACKGROUND: Centella asiatica (C. asiatica) was previously reported to have anti
      hyperglycemic effects in animal diabetic model rats. However, its activity on
      organ and tissue level remains unstudied. Our study aims at exploring the
      possible effects, C. asiatica extract and insoluble fiber has on carbohydrate
      absorption, insulin secretion, insulin sensitivity and glucose utilization.
      METHODS: For primary evaluation of anti-hyperglycemic activity, we measured
      Fasting Blood Glucose and performed Glucose Tolerance Test, in type 2 diabetic
      rats. To further study the pancreatic effect and glucose utilization, plasma
      insulin concentration, insulin secreted from isolated rat islets and liver
      glycogen were assayed. Effect on carbohydrate break down was assayed using
      intestinal disaccharidase enzyme, alpha-amylase inhibition assays and Six-Segment
      study of the GI tract. Effect of C. asiatica on glucose absorption was studied by
      an in-situ, perfused, intestinal model in rats and by glucose-fiber binding
      assay. Gastrointestinal motility was seen by a BaSO4 milk traverse test.
      Additionally, a complete lipid profile assay, after a chronic study, was
      conducted. RESULTS: C. asiatica showed no significant change in insulin secretion
      in-vivo and in isolated rat islets. Additionally, no effect of the extract was
      seen on liver glycogen deposition. Retarded glucose absorption was seen in the in
      situ perfused rat intestinal model at a dose. The extract was also found to
      inhibit action of both intestinal disaccharidase and alpha-amylase. This was
      confirmed, yet again, via the Six Segment study, where sucrose digestion was
      found to be inhibited throughout the length of the GI Tract. Significant glucose
      fiber binding was demonstrated in the in-vitro models. During the chronic study,
      body mass of C. asiatica treated Type 2 diabetic rats returned to normal and
      their polydipsic and polyphagic conditions were also improved. Chronic treatment
      of C. asiatica also improved subject's lipid profile. CONCLUSION: A combination
      of in-vitro, in-vivo and in-situ tests confirmed the anti-hyperglycemic activity
      of C. asiatica and its tissue level mechanism. Further study is required to fully
      elucidate the effect this extract or the active compounds have on the individual
      glucose transporters and the precise mechanism of glucose-fiber binding.

PMID- 24438381
TI  - Planned development and evaluation protocol of two versions of a web-based
      computer-tailored nutrition education intervention aimed at adults, including
      cognitive and environmental feedback.
AB  - BACKGROUND: Despite decades of nutrition education, the prevalence of unhealthy
      dietary patterns is still high and inequalities in intake between high and low
      socioeconomic groups still exist. Therefore, it is important to innovate and
      improve existing nutrition education interventions. This paper describes the
      development, design and evaluation protocol of a web-based computer-tailored
      nutrition education intervention for adults targeting fruit, vegetable, high
      energy snack and fat intake. This intervention innovates existing computer
      tailored interventions by not only targeting motivational factors, but also
      volitional and self-regulation processes and environmental-level factors.
      METHODS/DESIGN: The intervention development was guided by the Intervention
      Mapping protocol, ensuring a theory-informed and evidence-based intervention. Two
      versions of the intervention were developed: a basic version targeting knowledge,
      awareness, attitude, self-efficacy and volitional and self-regulation processes,
      and a plus version additionally addressing the home environment arrangement and
      the availability and price of healthy food products in supermarkets. Both
      versions consist of four modules: one for each dietary behavior, i.e. fruit,
      vegetables, high-energy snacks and fat. Based on the self-regulation phases, each
      module is divided into three sessions. In the first session, feedback on dietary
      behavior is provided to increase awareness, feedback on attitude and self
      efficacy is provided and goals and action plans are stated. In the second session
      goal achievement is evaluated, reasons for failure are explored, coping plans are
      stated and goals can be adapted. In the third session, participants can again
      evaluate their behavioral change and tips for maintenance are provided. Both
      versions will be evaluated in a three-group randomized controlled trial with
      measurements at baseline, 1-month, 4-months and 9-months post-intervention, using
      online questionnaires. Both versions will be compared with a generic nutrition
      information control condition. The primary outcomes are fruit, vegetable, high
      energy snack and fat intake. DISCUSSION: The evaluation study will provide
      insight into the short- and long-term efficacy of both intervention versions in
      adults. Additionally, differences in the efficacy among high- and low-educated
      people will be examined. If these interventions are effective, two well-developed
      interventions will become available for the implementation and promotion of
      healthy dietary patterns among both high- and low-educated adults in the
      Netherlands. TRIAL REGISTRATION: Dutch Trial Registry NTR3396.

PMID- 24438382
TI  - Liver transplantation in an adolescent with acute liver failure from acute
      lymphoblastic leukemia.
AB  - The most common identifiable causes of acute liver failure in pediatric patients
      are infection, drug toxicity, metabolic disease, and autoimmune processes. In
      many cases, the etiology of acute liver failure cannot be determined. Acute
      leukemia is an extremely rare cause of acute liver failure, and liver
      transplantation has traditionally been contraindicated in this setting. We report
      a case of acute liver failure in a previously healthy 15-yr-old male from pre-B
      cell acute lymphoblastic leukemia. He underwent liver transplantation before the
      diagnosis was established, and has subsequently received chemotherapy for pre-B
      cell acute lymphoblastic leukemia. He is currently alive 31 months post
      transplantation. The published literature describing acute lymphoblastic leukemia
      as a cause of acute liver failure is reviewed.

PMID- 24438383
TI  - Effect of lateral static load on immediately restored implants: histologic and
      radiographic evaluation in dogs.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of lateral static
      load in immediately restored implants in the canine mandible. MATERIAL AND
      METHODS: In 7 mongrel dogs, all premolars and the first molars were extracted
      bilaterally in the mandible. Two months after the extractions, 6 implants with
      sandblasted acid-etched surfaces were placed in each animal, 3 on each side.
      Randomly, two implants per side were immediately restored with an orthodontic
      expansion device that promoted lateral excessive static load (test group) or load
      (control) while the third implant of each side, remained submerged (unloaded
      group). These loaded devices were cleaned daily with chlorhexidine 0.12%, during
      the 4 months of study, when the animals were sacrificed and biopsies removed for
      histometric study. Intra-oral periapicals were made using positioners at the
      beginning and at the end of the study. RESULTS: Five implants from test group
      were lost in 3 dogs. Radiographically, there was a marginal bone loss of 3.68 +/-
      0.74 mm for the test group, 1.63 +/- 0.2 mm for the control group and 0.45 +/-
      0.5 mm for the unloaded group. Histometrically, the percentage of bone-to-implant
      contact (BIC%) was 35.52 +/- 7.32%, for the test group, 63.16 +/- 5.16% for the
      control group and 42.33 +/- 2.14% for the unloaded group. CONCLUSION: In
      conclusion, the excessive lateral static load negatively affected the behavior of
      peri-implant bone around immediate restored implants.

PMID- 24438384
TI  - Mindfulness based interventions in multiple sclerosis--a systematic review.
AB  - BACKGROUND: Multiple sclerosis (MS) is a stressful condition; depression,
      anxiety, pain and fatigue are all common problems. Mindfulness based
      interventions (MBIs) mitigate stress and prevent relapse in depression and are
      increasingly being used in healthcare. However, there are currently no systematic
      reviews of MBIs in people with MS. This review aims to evaluate the effectiveness
      of MBIs in people with MS. METHODS: Systematic searches were carried out in seven
      major databases, using both subject headings and key words. Papers were screened,
      data extracted, quality appraised, and analysed by two reviewers independently,
      using predefined criteria. Study quality was assessed using the Cochrane
      Collaboration risk of bias tool. Perceived stress was the primary outcome.
      Secondary outcomes include mental health, physical health, quality of life, and
      health service utilisation. Statistical meta-analysis was not possible.
      Disagreements were adjudicated by a third party reviewer. RESULTS: Three studies
      (n = 183 participants) were included in the final analysis. The studies were
      undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n
      = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%)
      participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting
      MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary
      progressive disease; and the remainder were unspecified. MBIs lasted 6-8 weeks;
      attrition rates were variable (5-43%); all employed pre- post- measures; two had
      longer follow up; one at 3, and one at 6 months. Socio-economic status of
      participants was not made explicit; health service utilisation and costs were not
      reported. No study reported on perceived stress. All studies reported quality of
      life (QOL), mental health (anxiety and depression), physical (fatigue, standing
      balance, pain), and psychosocial measures. Statistically significant beneficial
      effects relating to QOL, mental health, and selected physical health measures
      were sustained at 3- and 6- month follow up. CONCLUSION: From the limited data
      available, MBIs may benefit some MS patients in terms of QOL, mental health, and
      some physical health measures. Further studies are needed to clarify how MBIs
      might best serve the MS population.

PMID- 24438385
TI  - A comparison of the home-care and healthcare service use and costs of older
      Australians randomised to receive a restorative or a conventional home-care
      service.
AB  - Restorative home-care services, or re-ablement home-care services as they are now
      known in the UK, aim to assist older individuals who are experiencing
      difficulties in everyday living to optimise their functioning and reduce their
      need for ongoing home care. Until recently, the effectiveness of restorative home
      care services had only been investigated in terms of singular outcomes such as
      length of home-care episode, admission to hospital and quality of life. This
      paper reports on a more complex and perhaps more significant measure--the use and
      cost of the home-care and healthcare services received over the 2-year period
      following service commencement. Seven hundred and fifty older individuals
      referred for government-funded home care were randomly assigned to a restorative
      or standard service between June 2005 and August 2007. Health and aged care
      service data were sourced and linked via the Western Australian Data Linkage
      System. Restorative clients used fewer home-care hours (mean [SD], 117.3 [129.4]
      vs. 191.2 [230.4]), had lower total home-care costs (AU$5570 vs. AU$8541) and
      were less likely to be approved for a higher level of aged care (N [%], 171
      [55.2] vs. 249 [63.0]) during follow-up. They were also less likely to have
      presented at an emergency department (OR = 0.69, 95% CI = 0.50-0.94) or have had
      an unplanned hospital admission [OR (95% CI), 0.69 (0.50-0.95)]. Additionally,
      the aggregated health and home-care costs of the restorative clients were lower
      by a factor of 0.83 (95% CI 0.72-0.96) over the 2-year follow-up (AU$19,090 vs.
      AU$23,428). These results indicate that at a time when Australia is facing the
      challenges of population ageing and an expected increase in demand for health and
      aged care services, the provision of a restorative service when an older person
      is referred for home care is potentially a more cost-effective option than
      providing conventional home care.

PMID- 24438386
TI  - Acute effects of different volumes of dynamic stretching on vertical jump
      performance, flexibility and muscular endurance.
AB  - The purpose of this study was to examine the acute effects of different volumes
      of a dynamic stretching routine on vertical jump (VJ) performance, flexibility
      and muscular endurance (ME). Twenty-six males (age 22.2 +/- 1.3 years) performed
      three separate randomized conditions: (i) a control (CON) condition (5-min jog +
      12 min of resting), (ii) a 5-min jog + a dynamic stretching routine (DS1; 6.7 +/-
      1.3 min) and (iii) a 5-min jog + a dynamic stretching routine with twice the
      volume (DS2; 12.1 +/- 1.6 min). The dynamic stretching routine included 11
      exercises targeting the hip and thigh musculature. VJ performance (jump height
      and velocity) and flexibility were measured prior to and following all
      conditions, while ME was measured following all conditions. The DS1 and DS2
      conditions increased VJ height and velocity (P<0.01), while the CON condition did
      not change (P>0.05). When compared to the CON condition, the DS1 condition did
      not improve ME (P>0.05), whereas the DS2 condition resulted in a significant
      (15.6%) decrease in the number of repetitions completed (P<0.05). Flexibility
      increased following all conditions (P<0.01), while the DS1 condition was
      significantly greater (P<0.01) than the CON condition at post-testing. These
      results suggest that dynamic stretching routines lasting approximately 6-12 min
      performed following a 5-min jog resulted in similar increases in VJ performance
      and flexibility. However, longer durations of dynamic stretching routines may
      impair repetitive high-intensity activities.

PMID- 24438387
TI  - The epidemiology ontology: an ontology for the semantic annotation of
      epidemiological resources.
AB  - BACKGROUND: Epidemiology is a data-intensive and multi-disciplinary subject,
      where data integration, curation and sharing are becoming increasingly relevant,
      given its global context and time constraints. The semantic annotation of
      epidemiology resources is a cornerstone to effectively support such activities.
      Although several ontologies cover some of the subdomains of epidemiology, we
      identified a lack of semantic resources for epidemiology-specific terms. This
      paper addresses this need by proposing the Epidemiology Ontology (EPO) and by
      describing its integration with other related ontologies into a semantic enabled
      platform for sharing epidemiology resources. RESULTS: The EPO follows the OBO
      Foundry guidelines and uses the Basic Formal Ontology (BFO) as an upper ontology.
      The first version of EPO models several epidemiology and demography parameters as
      well as transmission of infection processes, participants and related procedures.
      It currently has nearly 200 classes and is designed to support the semantic
      annotation of epidemiology resources and data integration, as well as information
      retrieval and knowledge discovery activities. CONCLUSIONS: EPO is under active
      development and is freely available at https://code.google.com/p/epidemiology
      ontology/. We believe that the annotation of epidemiology resources with EPO will
      help researchers to gain a better understanding of global epidemiological events
      by enhancing data integration and sharing.

PMID- 24438388
TI  - Transient median and ulnar neuropathy associated with a microwave device for
      treating axillary hyperhidrosis.

PMID- 24438390
TI  - Successful percutaneous transluminal coronary angioplasty for acute myocardial
      infarction in a 12-year-old boy with fibromuscular dysplasia: a case report.
AB  - Acute myocardial infarction is rarely reported in children. Most of the cases are
      secondary to congenital anomalies or Kawasaki disease. Coronary artery total
      occlusion caused by fibromuscular dysplasia has never been reported in young
      children. Here we report a case of a 12-year-old boy with fibromuscular
      dysplasia, who underwent successful coronary intervention for acute myocardial
      infarction. 

PMID- 24438389
TI  - antibacTR: dynamic antibacterial-drug-target ranking integrating comparative
      genomics, structural analysis and experimental annotation.
AB  - BACKGROUND: Development of novel antibacterial drugs is both an urgent healthcare
      necessity and a partially neglected field. The last decades have seen a
      substantial decrease in the discovery of novel antibiotics, which combined with
      the recent thrive of multi-drug-resistant pathogens have generated a scenario of
      general concern. The procedures involved in the discovery and development of
      novel antibiotics are economically challenging, time consuming and lack any
      warranty of success. Furthermore, the return-on-investment for an antibacterial
      drug is usually marginal when compared to other therapeutics, which in part
      explains the decrease of private investment. RESULTS: In this work we present
      antibacTR, a computational pipeline designed to aid researchers in the selection
      of potential drug targets, one of the initial steps in antibacterial-drug
      discovery. The approach was designed and implemented as part of two publicly
      funded initiatives aimed at discovering novel antibacterial targets, mechanisms
      and drugs for a priority list of Gram-negative pathogens: Acinetobacter
      baumannii, Escherichia coli, Helicobacter pylori, Pseudomonas aeruginosa and
      Stenotrophomonas maltophilia. However, at present this list has been extended to
      cover a total of 74 fully sequenced Gram-negative pathogens. antibacTR is based
      on sequence comparisons and queries to multiple databases (e.g. gene
      essentiality, virulence factors) to rank proteins according to their potential as
      antibacterial targets. The dynamic ranking of potential drug targets can easily
      be executed, customized and accessed by the user through a web interface which
      also integrates computational analyses performed in-house and visualizable on
      site. These include three-dimensional modeling of protein structures and
      prediction of active sites among other functionally relevant ligand-binding
      sites. CONCLUSIONS: Given its versatility and ease-of-use at integrating both
      experimental annotation and computational analyses, antibacTR may effectively
      assist microbiologists, medicinal-chemists and other researchers working in the
      field of antibacterial drug-discovery. The public web-interface for antibacTR is
      available at 'http://bioinf.uab.cat/antibactr'.

PMID- 24438391
TI  - A year of centenary celebrations: a Black Swan's song.

PMID- 24438392
TI  - Role of the medical community in detecting and managing child abuse.

PMID- 24438393
TI  - Communication, confidentiality and consent in mental health care.

PMID- 24438396
TI  - Fifty years on . . . more action is still needed to end tobacco smoking in
      Australia.

PMID- 24438397
TI  - Psychotropic drug use in aged care facilities: a reflection of a systemic
      problem?

PMID- 24438398
TI  - Enhancing hepatitis C treatment in the custodial setting: a national roadmap.

PMID- 24438399
TI  - Challenges in health policy: the next 10 years.

PMID- 24438400
TI  - Challenges in health policy: the next 10 years.

PMID- 24438401
TI  - Investigating iron deficiency anaemia.

PMID- 24438402
TI  - Investigating iron deficiency anaemia.

PMID- 24438403
TI  - Investigating iron deficiency anaemia.

PMID- 24438404
TI  - "They liked it if you said you cried": how medical students perceive the teaching
      of professionalism.

PMID- 24438405
TI  - "They liked it if you said you cried": how medical students perceive the teaching
      of professionalism.

PMID- 24438406
TI  - "They liked it if you said you cried": how medical students perceive the teaching
      of professionalism.

PMID- 24438407
TI  - "They liked it if you said you cried": how medical students perceive the teaching
      of professionalism.

PMID- 24438408
TI  - "They liked it if you said you cried": how medical students perceive the teaching
      of professionalism.

PMID- 24438409
TI  - Fortnightly emergency department case-file audit for timely detection of missed
      cases of suspicious injury.

PMID- 24438410
TI  - Implementation of an HIV assessment tool leads to significant improvements in
      outpatient care.

PMID- 24438411
TI  - How well do NSW hospital data identify cases of heart failure?

PMID- 24438412
TI  - Gonorrhoea infection, reinfection and co-infection in men in inner Sydney: a
      population-based analysis.

PMID- 24438413
TI  - Changing trends in venous thromboembolism-related imaging in Western Australian
      teaching hospitals, 2002-2010.

PMID- 24438414
TI  - Changing trends in venous thromboembolism-related imaging in Western Australian
      teaching hospitals, 2002-2010.

PMID- 24438415
TI  - Association between tobacco plain packaging and Quitline calls: a population
      based, interrupted time-series analysis.
AB  - OBJECTIVES: To investigate whether the introduction of tobacco plain packaging in
      Australia from 1 October 2012 was associated with a change in the number of calls
      to the smoking cessation helpline, Quitline, and to compare this with the impact
      of the introduction of graphic health warnings from 1 March 2006. DESIGN AND
      SETTING: Whole-of-population interrupted time-series analysis in New South Wales
      and the Australian Capital Territory between 1 March 2005 and October 2006 for
      the comparator, graphic health warnings, and October 2011 and April 2013 for the
      intervention of interest, tobacco plain packaging. MAIN OUTCOME MEASURE: Weekly
      number of calls to the Quitline, after adjusting for seasonal trends, anti
      tobacco advertising, cigarette costliness and the number of smokers in the
      community. RESULTS: There was a 78% increase in the number of calls to the
      Quitline associated with the introduction of plain packaging (baseline, 363/week;
      peak, 651/week [95% CI, 523-780/week; P < 0.001]). This peak occurred 4 weeks
      after the initial appearance of plain packaging and has been prolonged. The 2006
      introduction of graphic health warnings had the same relative increase in calls
      (84%; baseline, 910/week; peak, 1673/week [95% CI, 1383-1963/week; P < 0.001])
      but the impact of plain packaging has continued for longer. CONCLUSIONS: There
      has been a sustained increase in calls to the Quitline after the introduction of
      tobacco plain packaging. This increase is not attributable to anti-tobacco
      advertising activity, cigarette price increases nor other identifiable causes.
      This is an important incremental step in comprehensive tobacco control.

PMID- 24438416
TI  - Potentially avoidable neonatal retrievals in New South Wales: a retrospective
      analysis.
AB  - OBJECTIVE: To identify areas for improvement in outcomes in retrieved newborns by
      reviewing newborn retrieval activity and evaluating potentially avoidable
      retrievals from each referring hospital stratified by the level of service
      delivery over the study period. DESIGN: A retrospective analysis of newborn
      retrievals from 1 January 2006 to 31 December 2009. SETTING: Newborn and
      Paediatric Emergency Transport Service (NETS). PARTICIPANTS: Newborns less than
      72 hours old retrieved by NETS in the study period. Each retrieval was classified
      as potentially avoidable, unavoidable or unclassified, based on predefined
      criteria. MAIN OUTCOME MEASURES: Newborn retrieval rates (per 10,000 live births)
      and potentially avoidable retrievals for each referring hospital level and
      overall. RESULTS: There were 2494 newborn retrievals over the study period, with
      an annual mean of 623 total and 30 potentially avoidable retrievals. There was a
      reduction in the potentially avoidable retrieval rate (per 10,000 live births)
      over the study period (from 3.9 in 2006 and 4.2 in 2007 to 2.2 in 2008 and 2.3 in
      2009) despite an increase in the total retrieval rate over the same time.
      Discretionary caesarean, defined as elective (pre-labour) caesarean section
      without documented fetal or maternal indications before 39 completed weeks of
      gestation, accounted for two-thirds of the potentially avoidable retrievals.
      CONCLUSIONS: Potentially avoidable retrievals were a small but significant
      proportion and are becoming less frequent. Discretionary caesarean is the most
      common cause of potentially avoidable retrieval. Strict implementation of the
      elective caesarean section policy directive has the potential to reduce morbidity
      and the costs related to retrieval.

PMID- 24438417
TI  - Maladministrations in nuclear medicine: revelations from the Australian Radiation
      Incident Register.
AB  - OBJECTIVE: To describe the incidence, type, causes and consequences of nuclear
      medicine maladministrations. SETTING AND PARTICIPANTS: Review of prospectively
      acquired maladministration reports within the Australian Radiation Incident
      Register (ARIR), a mandatory incident register managed by the Australian
      Radiation Protection and Nuclear Safety Agency. MAIN OUTCOME MEASURES: Individual
      reports from 2007 to 2011 were evaluated for dose of radiation exposure and type,
      cause and consequence of maladministrations. Incidence was estimated using data
      from Medicare Australia. RESULTS: There were 149 maladministrations and the
      estimated incidence was 5.8 per 100,000 nuclear medicine procedures (95% CI, 5.0
      6.9). About half of all maladministrations (48%) arose from an incorrect
      radiopharmaceutical being prepared and/or dispensed. Other causes included
      mistakenly injecting the wrong radiopharmaceutical because of inattention (n =
      27; 18.1%); extravasations, failures in equipment or procedure leading to a non
      diagnostic study (n = 25; 16.8%); misinterpreting a request form and performing
      an incorrect procedure (n = 13; 8.7%); or injecting an incorrect patient (n = 13;
      8.7%). ARIR reports focused on active rather than latent causes. Most (n = 147)
      maladministrations occurred following diagnostic procedures, and the mean
      effective radiation dose was 7.9 mSv (range, 0.015-45 mSv). Two therapeutic
      maladministrations likely caused unintended organ injury. CONCLUSIONS: The ARIR
      provides unique insight into the type, causes and complications of
      maladministrations in Australia. Nearly all maladministrations occur in a
      diagnostic context, and the risk of patient harm appears low. Among active
      causes, radiopharmaceutical preparation and dispensation, and medical supervision
      before injection merit attention. The ARIR could be refined by attending to
      latent errors, addressing possible underreporting and securing more complete
      Medicare data.

PMID- 24438418
TI  - Workplace-based assessment for international medical graduates: at what cost?
AB  - OBJECTIVE: To estimate the cost of resources required to deliver a program to
      assess international medical graduates (IMGs) in Newcastle, Australia, known as
      the Workplace Based Assessment (WBA) Program. DESIGN AND SETTING: A costing study
      to identify and evaluate the resources required and the overheads of delivering
      the program for a cohort of 15 IMGs, based on costs in 2012. MAIN OUTCOME
      MEASURES: Labour-related costs. RESULTS: The total cost in 2012 for delivering
      the program to a typical cohort of 15 candidates was $243,384. This equated to an
      average of $16,226 per IMG. After allowing for the fees paid by IMGs, the WBA
      Program had a deficit of $153,384, or $10,226 per candidate, which represents the
      contribution made by the health system. CONCLUSION: The cost per candidate to the
      health system of this intensive WBA program for IMGs is small.

PMID- 24438419
TI  - Do outlier inpatients experience more emergency calls in hospital? An
      observational cohort study.
AB  - OBJECTIVE: To determine the effect of spending time as an outlier (ie, an
      inpatient who spends time away from his or her "home" ward) on the frequency of
      emergency calls for patients admitted to a tertiary referral hospital. DESIGN,
      SETTING AND PATIENTS: Observational cohort study of all patients admitted to a
      university-affiliated tertiary referral hospital in Melbourne, Victoria, between
      1 July 2009 and 30 November 2011. MAIN OUTCOME MEASURE: The number of emergency
      calls per hospital admission, with reference to location within the hospital.
      RESULTS: There were 58,158 admissions during the study period. The median age of
      admitted patients was 61 years, 55% were male, and the inhospital mortality was
      1.40%. In 11,034 admissions (18.97%), patients spent time as outliers. Inhospital
      mortality was 2.57% in the outlier group versus 1.12% in the non-outlier group (P
      < 0.001). After adjusting for age, same-day admission, 10-year predicted
      mortality, interhospital transfer and high-risk clinical units, outlier status
      was associated with a 53% increase in emergency calls (P < 0.001). CONCLUSIONS:
      This study found a strong association between time spent away from a patient's
      home ward and the number of emergency calls. We postulate that outlier patients
      are at risk as they may have therapeutic and monitoring needs that are only
      available on their home ward. With increasing pressure to move patients out of
      the emergency department, the number of outlier patients may increase.

PMID- 24438420
TI  - Topical timolol for a chronic ulcer--a case with its own control.

PMID- 24438421
TI  - Ancient Egyptian surgery.

PMID- 24438422
TI  - Leaders in disguise--the unexpected tomorrows of global health.

PMID- 24438424
TI  - Spontaneous atraumatic vertebral artery occlusion due to physiological cervical
      extension: case report.
AB  - Vertebral artery (VA) occlusion is a serious and potentially life-threatening
      occurrence. Bow hunter's syndrome, a mechanical occlusion of the VA due to
      physiological head rotation, has been well described in the medical literature.
      However, mechanical VA compression due to routine flexion or extension of the
      neck has not been previously reported. The authors present the unique case of a
      woman without any history of trauma who had multiple posterior fossa strokes and
      was found to have dynamic occlusion of her right VA visualized via cerebral
      angiogram upon extension of her neck. This occlusion was attributed to
      instability at the occipitocervical junction in a patient with a previously
      unknown congenital fusion of both the occiput to C-1 and C-2 to C-3. An occiput
      to C-3 fusion was performed to stabilize her cervical spine and minimize the
      dynamic vascular compression. A postoperative angiogram showed no evidence of
      restricted flow with flexion or extension of the neck. This case emphasizes the
      importance of considering symptoms of vertebrobasilar insufficiency as a result
      of physiological head movement. The authors also review the literature on VA
      compression resulting from physiological head movement as well as strategies for
      clinical diagnosis and treatment. 

PMID- 24438425
TI  - Editorial: Predicting surgical satisfaction using artificial neural networks.

PMID- 24438426
TI  - High cervical arteriovenous fistulas fed by dural and spinal arteries and
      draining into a single medullary vein: report of 3 cases.
AB  - OBJECT: The authors previously reported a case of complex arteriovenous fistula
      (AVF) at C-1 with multiple dural and spinal feeders that were linked with a
      common medullary venous channel. The purpose of the present study was to collect
      similar cases and analyze their angioarchitecture to gain a better understanding
      of this malformation. METHODS: Three such cases, affecting 2 males and 1 female
      in their 60s who had presented with hematomyelia (2) or progressive myelopathy
      (1), were treated surgically, and the operative findings from all 3 cases were
      compared using digital subtraction angiography (DSA) to determine the
      angioarchitecture. RESULTS: The C-1 and C-2 radicular arteries and anterior and
      posterior spinal arteries supplied feeders to a single medullary draining vein in
      various combinations and via various routes. The drainage veins ran along the
      affected ventral nerve roots and lay ventral to the spinal cord. The sites of
      shunting to the vein were multiple: dural, along the ventral nerve root in the
      subarachnoid space, and on the spinal cord, showing a vascular structure typical
      of dural AVF, that is, a direct arteriovenous shunt near the spinal root sleeve
      fed by one or more dural arteries and ending in a single draining vein, except
      for intradural shunts fed by feeders from the spinal arteries. In 2 cases with
      hemorrhagic onset the drainer flowed rostrally, and in 1 case associated with
      congestive myelopathy the drainer flowed both rostrally and caudally.
      Preoperative determination of the shunt sites and feeding arteries was difficult
      because of complex recruitment of the feeders and multiple shunt sites. The
      angioarchitecture in these cases was clarified postoperatively by meticulous
      comparison of the DSA images and operative video. Direct surgical intervention
      led to a favorable outcome in all 3 cases. CONCLUSIONS: A high cervical complex
      AVF has unique angioarchitectural characteristics different from those seen in
      the other spinal regions.

PMID- 24438427
TI  - Conus medullaris and cauda equina tumors: clinical presentation, prognosis, and
      outcome after surgical treatment: clinical article.
AB  - OBJECT: Intradural cauda equina and conus medullaris tumors (CECMTs) are rare.
      Only a few large clinical series exist to date. Therefore, clinical symptoms,
      surgical complications, and outcomes are poorly understood. The aim of the
      present study was to evaluate outcome after surgery of CECMTs and to identify the
      factors associated with a worse clinical prognosis based on the results of a
      series with sufficiently high number of cases. METHODS: All cases of intradural
      CECMTs treated surgically at the authors' department between March 2006 and May
      2012 were retrospectively evaluated. Arachnoid cysts and multifocal tumors were
      excluded. Sixty-eight adult patients met the inclusion criteria (35 female and 33
      male patients; median age 56 years). Follow-up data were available for 72% (n =
      49) in a median period of 9 months. RESULTS: Overall, 18 tumors were located
      intramedullary and 50 extramedullary. The majority were nerve sheath tumors (n =
      27), ependymomas (n = 17), and meningiomas (n = 9). The most common preoperative
      symptom was pain. The rate of new transient postoperative impairment was 18% (n =
      12), and new permanent deficits were observed in only 6% (n = 4). Overall
      neurological improvement was achieved in 62%. The reversibility of preoperative
      symptoms was related to the interval between the time of symptom onset and the
      time of surgery and to the presence of preoperative neurological deficits.
      Surgery of ependymoma and carcinoma metastases was associated with a higher rate
      of morbidity. CONCLUSIONS: Intradural CECMTs present as a group of tumors with
      varying histological features and clinical symptoms. Symptomatic manifestation is
      usually unspecific, mimicking degenerative lumbar spine syndromes. Despite a
      significant risk of transient deterioration, early surgery is advisable because
      more than 94% of patients maintain at least their preoperative status and more
      than 60% improve during follow-up. The reversibility of preoperative symptoms is
      related to the duration between symptom onset and surgery and to the presence of
      preoperative neurological deficits. The prognosis for recovery from cauda equina
      or conus medullaris syndrome is less favorable than for other deficits. Surgery
      of ependymoma is associated with a higher morbidity rate than other benign
      entities.

PMID- 24438428
TI  - Use of artificial neural networks to predict surgical satisfaction in patients
      with lumbar spinal canal stenosis: clinical article.
AB  - OBJECT: The purpose of this study was to develop an artificial neural network
      (ANN) model for predicting 2-year surgical satisfaction, and to compare the new
      model with traditional predictive tools in patients with lumbar spinal canal
      stenosis. METHODS: The 2 prediction models included an ANN and a logistic
      regression (LR) model. The patient age, sex, duration of symptoms, walking
      distance, visual analog scale scores of leg pain or numbness, the Japanese
      Orthopaedic Association score, the Neurogenic Claudication Outcome Score, and the
      stenosis ratio values were determined as the input variables for the ANN and LR
      models that were developed. Patient surgical satisfaction was recorded using a
      standardized measure. The ANNs were fed patient data to predict 2-year surgical
      satisfaction based on several input variables. Sensitivity analysis was applied
      to the ANN model to identify the important variables. The receiver operating
      characteristic-area under curve (ROC-AUC), Hosmer-Lemeshow statistics, and
      accuracy rate were calculated for evaluating the 2 models. RESULTS: A total of
      168 patients (59 male, 109 female; mean age 59.8 +/- 11.6 years) were divided
      into training (n = 84), testing (n = 42), and validation (n = 42) data sets.
      Postsurgical satisfaction was 88.7% at 2-year follow-up. The stenosis ratio was
      the important variable selected by the ANN. The ANN model displayed a better
      accuracy rate in 96.9% of patients, a better Hosmer-Lemeshow statistic in 42.4%
      of patients, and a better ROC-AUC in 80% of patients, compared with the LR model.
      CONCLUSIONS: The findings show that an ANN can predict 2-year surgical
      satisfaction for use in clinical application and is more accurate compared with
      an LR model.

PMID- 24438429
TI  - Mental health literacy about schizophrenia: a survey of Portuguese youth.
AB  - AIM: Mental health literacy about psychotic disorders, specifically
      schizophrenia, may assist in appropriate help seeking and early intervention,
      preventing the exacerbation of symptoms and improving health outcomes in the
      medium and long term. The aim of this study was to characterize the level of
      mental health literacy of Portuguese youth concerning schizophrenia. METHODS: A
      mental health literacy questionnaire was administered to a random sample of
      Portuguese youth aged 14-24 years. This questionnaire evaluated the following
      components: recognition of disorders, knowledge about professionals and
      treatments available, knowledge about the effectiveness of self-help strategies,
      knowledge and skills to support and provide first aid to others, and knowledge of
      how to prevent mental disorders. RESULTS: There were 4938 adolescents and young
      adults who participated in the study. Schizophrenia or psychosis was recognized
      by 42.17% and 22.21%, respectively. Most young people recognized the potential
      helpfulness of family doctors, psychologists, psychiatrists and mental health
      services. There was also widespread belief in the potential helpfulness of family
      and friends, and lifestyle changes. However, teachers were not generally seen as
      a source of help. Appropriate mental health first-aid strategies were commonly
      endorsed, but there was a reluctance to ask about suicidal feelings and many
      endorsed speaking to the person firmly. Lifestyle factors were also commonly
      believed to be preventative. CONCLUSIONS: Although many Portuguese youth have
      beliefs that may assist early intervention, there was a substantial minority who
      did not. Given the central role of teachers in the lives of young people, it is
      notable that they were not seen as a potential source of help. Mental health
      first-aid skills of young people also need improvement.

PMID- 24438430
TI  - A national population-based assessment of 2007-2008 election-related violence in
      Kenya.
AB  - BACKGROUND: Following the contested national elections in 2007, violence occurred
      throughout Kenya. The objective of this study was to assess the prevalence,
      characteristics, and health consequences of the 2007-2008 election-related
      violence. METHODS: A cross-sectional, national, population-based cluster survey
      of 956 Kenyan adults aged >= 18 years was conducted in Kenya in September 2011
      utilizing a two-stage 90 x 10 cluster sample design and structured interviews and
      questionnaires. Prevalence of all forms of violence surrounding the 2007 election
      period, symptoms of major depressive disorder (MDD) and posttraumatic stress
      disorder (PTSD), and morbidity related to sexual and physical violence were
      assessed. RESULTS: Of 956 households surveyed, 916 households participated
      (response rate 95.8%). Compared to pre-election, election-related sexual violence
      incidents/1000 persons/year increased over 60-fold (39.1-2370.1; p < .001) with a
      concurrent 37-fold increase in opportunistic sexual violence (5.2-183.1; p <
      .001). Physical and other human rights violations increased 80-fold (25.0-1987.1;
      p < .001) compared to pre-election. Overall, 50% of households reported at least
      one physical or sexual violation. Households reporting violence were more likely
      to report violence among female household members (66.6% vs. 58.1%; p = .04) or
      among the Luhya ethnic group (17.0% vs. 13.8%; p = 0.03). The most common
      perpetrators of election-related sexual violence were reported to be affiliated
      with government or political groups (1670.5 incidents/1000 persons per year); the
      Kalenjin ethnic group for physical violations (54.6%). Over thirty percent of
      respondents met MDD and PTSD symptom criteria; however, symptoms of MDD (females,
      63.3%; males, 36.7%; p = .01) and suicidal ideation (females, 68.5%; males,
      31.5%; p = .04) were more common among females. Substance abuse was more common
      among males (males, 71.2%; females, 28.8%; p < .001). CONCLUSION: On a national
      level in Kenya, politically-motivated and opportunistic sexual and physical
      violations were commonly reported among sampled adults with associated health and
      mental health outcomes.

PMID- 24438431
TI  - Resurrecting social infrastructure as a determinant of urban tuberculosis control
      in Delhi, India.
AB  - BACKGROUND: The key to universal coverage in tuberculosis (TB) management lies in
      community participation and empowerment of the population. Social infrastructure
      development generates social capital and addresses the crucial social
      determinants of TB, thereby improving program performance. Recently, there has
      been renewed interest in the concept of social infrastructure development for TB
      control in developing countries. This study aims to revive this concept and
      highlight the fact that documentation on ways to operationalize urban TB control
      is required from a holistic development perspective. Further, it explains how
      development of social infrastructure impacts health and development outcomes,
      especially with respect to TB in urban settings. METHODS: A wide range of
      published Government records pertaining to social development parameters and TB
      program surveillance, between 2001 and 2011 in Delhi, were studied. Social
      infrastructure development parameters like human development index along with
      other indicators reflecting patient profile and habitation in urban settings were
      selected as social determinants of TB. These include adult literacy rates, per
      capita income, net migration rates, percentage growth in slum population, and
      percentage of urban population living in one-room dwelling units. The impact of
      the Revised National Tuberculosis Control Program on TB incidence was assessed as
      an annual decline in new TB cases notified under the program. Univariate linear
      regression was employed to examine the interrelationship between social
      development parameters and TB program outcomes. RESULTS: The decade saw a
      significant growth in most of the social development parameters in the State. TB
      program performance showed 46% increment in lives saved among all types of TB
      cases per 100,000 population. The 7% reduction in new TB case notifications from
      the year 2001 to 2011, translates to a logarithmic decline of 5.4 new TB cases
      per 100,000 population. Except per capita income, literacy, and net migration
      rates, other social determinants showed significant correlation with decline in
      new TB cases per 100,000 population. CONCLUSIONS: Social infrastructure
      development leads to social capital generation which engenders positive growth in
      TB program outcomes. Strategies which promote social infrastructure development
      should find adequate weightage in the overall policy framework for urban TB
      control in developing countries.

PMID- 24438432
TI  - Impact of the traditional Mediterranean diet on the Framingham risk score and the
      metabolic syndrome according to sex.
AB  - BACKGROUND: The traditional Mediterranean diet (MedDiet) has been recognized as a
      food pattern with beneficial effects on cardiovascular health. However, even if
      sex-related differences in the cardiovascular response to diet have been
      previously highlighted, the existence of such differences in the impact of the
      MedDiet on the global cardiovascular risk has not been yet investigated. This
      study examined sex differences in the global cardiovascular impact of a 4-week
      isoenergetic controlled MedDiet using the Framingham risk score and the National
      Cholesterol Education Program (NCEP) metabolic syndrome criteria. METHODS: This
      study included 38 men and 32 premenopausal women (24-53 years) who had slightly
      elevated low-density lipoprotein cholesterol (LDL-C) concentrations (between 3.4
      and 4.9 mmol/L) or total cholesterol-to-high-density lipoprotein cholesterol (HDL
      C) ratios >=5.0. Cardiovascular risk factors were measured before and after the
      controlled MedDiet. RESULTS: A time effect (P=0.04) was found for the Framingham
      risk score, with both men and women showing a nonsignificant decrease in response
      to the MedDiet. No time effect was found for the prevalence of the metabolic
      syndrome and the number of metabolic syndrome criteria that were met by
      participants (P>0.05). However, a time effect was noted for the continuous
      metabolic syndrome score (P=0.008), with nonsignificant decreases in both men and
      women. No sex-by-time interaction was noted for any of variables studied
      (P>0.05). CONCLUSIONS: Results from this study suggest that the global
      cardiovascular impact of the MedDiet, as assessed by the Framingham risk score
      and metabolic syndrome criteria, is not significantly different in men than in
      premenopausal women in isoenergetic conditions.

PMID- 24438433
TI  - Research and development productivity map: visualization of industry status.
AB  - WHAT IS KNOWN AND OBJECTIVE: Decline in research and development (R&D)
      productivity and changes in the business environment have led to pharmaceutical
      company management to strive to improve R&D productivity. This decline is widely
      considered to be a major cause of industry consolidation and has received
      increased scholarly attention. This study aims to construct an R&D productivity
      map to visualize the industry's R&D productivity and to identify similarity in
      corporate actions with a view to investigate whether there is a relationship
      between deterioration in R&D productivity and industry consolidation. METHODS:
      Research and development productivity is decomposed into two subprocesses to
      measure productivity: R&D efficiency and R&D effectiveness, and scores were
      calculated using a two-stage data envelopment analysis (DEA). The map is then
      constructed by projecting outputs. To identify any relationship between DEA
      scores and merger and acquisition transactions, a multiple regression model is
      employed. RESULTS AND DISCUSSION: Data on 21 global pharmaceutical companies,
      statistical results indicated that companies with lower R&D efficiency scores
      were more likely to engage in consolidation. Three US companies that were least
      successful in terms of R&D effectiveness, as measured by our indicators, were
      either acquired or changed their business model. CONCLUSION: The R&D productivity
      map is a useful means for visualizing productivity among companies. By grouping
      companies into four groups, behavioural commonalities can be observed. The R&D
      productivity map should be useful for monitor the industry's productivity and
      help to improve it.

PMID- 24438434
TI  - Quality of helping behaviours of members of the public towards a person with a
      mental illness: a descriptive analysis of data from an Australian national
      survey.
AB  - BACKGROUND: Courses such as Mental Health First Aid equip members of the public
      to perform appropriate helping behaviours towards people experiencing a mental
      illness or mental health crisis. However, studies investigating the general
      public's knowledge and skills in relation to assisting a person with a mental
      illness are rare. This study assesses the quality of mental health first aid
      responses by members of the Australian public using data from a national survey.
      METHODS: Participants in a national survey of mental health literacy were
      assigned one of six vignettes (depression, depression with suicidal thoughts,
      early schizophrenia, chronic schizophrenia, social phobia or post-traumatic
      stress disorder) and asked an open-ended question about how they would help the
      character in the vignette. The 6,019 respondents were also asked if and how they
      had helped a person in real life with a similar problem. Responses to these
      questions were scored using a system based on an action plan developed from
      expert consensus guidelines on mental health first aid. RESULTS: The quality of
      responses overall was poor, with participants scoring an average of 2 out of 12.
      The most commonly reported actions for both questions were listening to the
      person, providing support and information and encouraging them to seek
      appropriate professional help. Actions such as assessing and assisting with
      crisis were rarely mentioned, even for the depression with suicidal thoughts
      vignette. CONCLUSIONS: The quality of the Australian public's mental health first
      aid knowledge and skills requires substantial improvement. Particular attention
      should be given to helping people recognise that anxiety disorders such as social
      phobia require professional help and to improving responses to a suicidal person.

PMID- 24438436
TI  - Hantavirus disease in Germany due to infection with Dobrava-Belgrade virus
      genotype Kurkino.
AB  - Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by
      different Apodemus mice as reservoir hosts and causing haemorrhagic fever with
      renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV,
      associated with the striped field mouse, Apodemus agrarius, is prevalent. This
      paper presents the first extensive study of the serological and molecular
      diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central
      Europe. Serum samples from 570 German patients living in the habitat of A.
      agrarius (north and northeast Germany) and exhibiting febrile disease, were
      analysed. All samples were tested by ELISA, subsets of samples were also analysed
      by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was
      confirmed as DOBV-infected. The virus neutralization assay allowed a reliable
      identification of DOBV antibodies during both acute and convalescent phases of
      infection. However, differentiation of relevant DOBV genotypes was not possible
      by neutralization test but required molecular analysis. Whereas DOBV IgM
      antibodies tend to persist in the infected organism, RNAaemia seems to be short.
      Nucleotide sequences were amplified from four patients, and their analysis
      demonstrated infection by DOBV-Kurkino. With respect to the initial results, the
      high degree of identity of local patient-derived and A. agrarius-derived virus
      sequences may allow a closer allocation of the geographical place where the human
      infection occurred. In contrast to moderate/severe HFRS caused by the DOBV
      genotypes Dobrava or Sochi, all available data showed a mild clinical course of
      HFRS caused by DOBV-Kurkino infection without lethal outcomes.

PMID- 24438435
TI  - Human body preservation - old and new techniques.
AB  - This review deals with the art of (anatomical) embalming. The first part contains
      a brief historical review of the history of embalming, starting with ancient
      cultures such as the Egyptians and the lesser known Chinchorro culture, then
      going down the centuries and describing the anatomical techniques developed over
      the last two centuries. The second part deals in detail with the chemicals used
      for embalming purposes. The third part deals with several approaches to
      evaluating embalming methods, their suitability for biomechanical testing,
      antimicrobial properties, histological appearance, and usability. The fourth and
      final part analyze the European Biocidal Products Directive (98/8/EC) in the
      light of embalming. 

PMID- 24438437
TI  - Influence of preoperative anti-HLA antibodies on short- and long-term graft
      survival in recipients with or without rituximab treatment.
AB  - We investigated the relationship between preoperative anti-HLA antibodies (donor
      specific antibody, DSA) and the graft survival rate in recipients who had or had
      not received rituximab (Rit) treatment. The subjects were categorized into four
      groups as follows: DSA+Rit-, n = 39; DSA-Rit-, n = 121; DSA+Rit+, n = 74; and DSA
      Rit+, n = 47. We examined the influence of preoperative DSA on the incidence of
      graft rejection and the survival rate of recipients who had or who had not
      received rituximab before transplantation. The 6-month acute rejection rates
      based on graft biopsies were 39%, 19%, 15%, and 0% for the DSA+Rit-, DSA-Rit-,
      DSA+Rit+, and DSA-Rit+ groups. The rates of chronic antibody-mediated rejection
      after more than 6 months were 50%, 22%, 18%, and 0%. The 5-year graft survival
      rate was significantly lower in the DSA+Rit- group (84%) than in the other groups
      (95% for DSA-Rit-, 98% for DSA+Rit+, and 91% for DSA-Rit+). The rate of the
      appearance of de novo anti-HLA antibodies was higher in the groups that did not
      receive rituximab treatment. The rate of graft loss associated with chronic
      antibody-mediated rejection was also higher in the DSA+Rit- group than in the
      other groups (P = 0.01). The presence of DSA and the administration of rituximab
      had strong impacts on not only short-term graft rejection, but also long-term
      graft rejection and its association with the graft survival time.

PMID- 24438439
TI  - Dynamical density delay maps: simple, new method for visualising the behaviour of
      complex systems.
AB  - BACKGROUND: Physiologic signals, such as cardiac interbeat intervals, exhibit
      complex fluctuations. However, capturing important dynamical properties,
      including nonstationarities may not be feasible from conventional time series
      graphical representations. METHODS: We introduce a simple-to-implement
      visualisation method, termed dynamical density delay mapping ("D3-Map" technique)
      that provides an animated representation of a system's dynamics. The method is
      based on a generalization of conventional two-dimensional (2D) Poincare plots,
      which are scatter plots where each data point, x(n), in a time series is plotted
      against the adjacent one, x(n + 1). First, we divide the original time series,
      x(n) (n = 1,..., N), into a sequence of segments (windows). Next, for each
      segment, a three-dimensional (3D) Poincare surface plot of x(n), x(n + 1),
      h[x(n),x(n + 1)] is generated, in which the third dimension, h, represents the
      relative frequency of occurrence of each (x(n),x(n + 1)) point. This 3D Poincare
      surface is then chromatised by mapping the relative frequency h values onto a
      colour scheme. We also generate a colourised 2D contour plot from each time
      series segment using the same colourmap scheme as for the 3D Poincare surface.
      Finally, the original time series graph, the colourised 3D Poincare surface plot,
      and its projection as a colourised 2D contour map for each segment, are animated
      to create the full "D3-Map." RESULTS: We first exemplify the D3-Map method using
      the cardiac interbeat interval time series from a healthy subject during sleeping
      hours. The animations uncover complex dynamical changes, such as transitions
      between states, and the relative amount of time the system spends in each state.
      We also illustrate the utility of the method in detecting hidden temporal
      patterns in the heart rate dynamics of a patient with atrial fibrillation. The
      videos, as well as the source code, are made publicly available. CONCLUSIONS:
      Animations based on density delay maps provide a new way of visualising dynamical
      properties of complex systems not apparent in time series graphs or standard
      Poincare plot representations. Trainees in a variety of fields may find the
      animations useful as illustrations of fundamental but challenging concepts, such
      as nonstationarity and multistability. For investigators, the method may
      facilitate data exploration.

PMID- 24438438
TI  - Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non
      alcoholic fatty liver disease in postmenopausal women and middle aged men--the
      role of gut microbiota composition: study protocol for the AELC randomized
      controlled trial.
AB  - BACKGROUND: Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are
      associated with an unhealthy lifestyle and pose extremely high costs to the
      healthcare system. In this study, we aim to explore whether individualized
      aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect
      hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota
      composition and other post-interventional effects. METHODS/DESIGN: A 6-month
      randomized intervention with 6-month follow-up is conducted from January 2013 to
      December 2015. The target sample size for intervention is 200 postmenopausal
      women and middle-aged men aged 50-65 year-old with pre-diabetes and NAFLD. The
      qualified subjects are randomized into 4 groups with 50 subjects in each group: 1
      = AEx, 2 = LCh, 3 = AEx + LCh, and 4 = control. In addition, two age-matched
      reference groups (5 = pre-diabetes without NAFLD (n = 50) and 6 = Healthy without
      pre-diabetes or NAFLD (n = 50)) are included. The exercise program consists of
      progressive and variable aerobic exercise (intensity of 60 to 75% of initial
      fitness level, 3-5 times/week and 30-60 min/time). The diet program includes
      dietary consultation plus supplementation with a special lunch meal (40% of total
      energy intake/day) which aims to reduce the amount of carbohydrate consumption
      (30%). The control and reference groups are advised to maintain their habitual
      habits during the intervention. The primary outcome measures are HFC, serum
      metabolomics and gut microbiota composition. The secondary outcome measures
      include body composition and cytokines. In addition, socio-psychological aspects,
      social support, physical activity and diet will be performed by means of
      questionnaire and interview. DISCUSSION: Specific individualized exercise and
      diet intervention in this study offers a more efficient approach for liver fat
      reduction and diabetes prevention via modification of gut microbiota composition.
      Besides, the study explores the importance of incorporating fitness assessment
      and exercise in the management of patients with pre-diabetes and fatty liver
      disorders. If our program is shown to be effective, it will open new strategies
      to combat these chronic diseases. TRIAL REGISTRATION: Current Controlled Trials:
      ISRCTN42622771.

PMID- 24438440
TI  - Reduced ATG-F dosage for induction in pediatric renal transplantation: a single
      center experience.
AB  - Rabbit antithymocyte globulin (ATG-F) is an extensively used induction agent. To
      our knowledge, no study to date has assessed reduced ATG-F dosage in children
      undergoing renal transplantation. This was a retrospective analysis of pediatric
      renal recipients in the Department of Kidney Transplantation, The First
      Affiliated Hospital of Zhengzhou University, from May 2007 to February 2013.
      Thirty-nine children underwent renal transplantation including 25 living related
      and 14 cardiac deceased donor transplantation. Each recipient received ATG-F 1.5
      mg/kg/d once daily for 4 days. Of the 39 recipients, five (12.8%) showed delayed
      graft function, including one of 25 recipients (4%) of living donor and four of
      14 recipients (28.6%) of deceased donor transplantation (p < 0.05). Six of the 39
      recipients (15.4%) showed acute rejection on renal biopsy. Follow-up in these
      children ranged from 6 to 87 months. The one-, three-, and five-yr recipients and
      grafts survival rates postoperation were each 94.9% and 97.3%, 97.3%, and 94.6%,
      respectively. The incidence of postoperative infection was 35.9% (14/39), and did
      not differ significantly in the living related and deceased donor groups (p >
      0.05). Low-dose ATG-F can be safely used as an immune induction agent in
      pediatric renal transplantation.

PMID- 24438441
TI  - Full-length sequence of a novel null allele HLA-A*11:69N identified in a Chinese
      individual.
AB  - We describe here a novel null allele of human leukocyte antigen gene, A*11:69N,
      which was initially found in a blood donor from China. 

PMID- 24438442
TI  - Smoking and the risk of peri-implantitis. A systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the
      role of smoking as a risk factor for peri-implantitis. MATERIAL AND METHODS: Six
      electronic databases and a manual search resulted in 5876 unique publications.
      After selection, only seven studies were included in the systematic review.
      Dichotomous data were expressed as risk ratios (RRs) and 95% confidence intervals
      (CIs). A generic inverse variance statistical model was used. Due to the expected
      interstudy heterogeneity, a random effect model was used for both data types.
      Heterogeneity was assessed with the Cochrane chi(2) and I(2) tests. The pooled
      effect was considered significant for a P-value <0.05. RESULTS: The implant-based
      meta-analysis revealed a higher and significant risk of peri-implantitis in
      smokers (RR: 2.1, 95% CI: 1.34-3.29, P = 0.001) compared with nonsmokers, but the
      patient-based meta-analysis did not reveal any significant differences for risk
      of peri-implantitis in smokers (RR: 1.17, 95% CI: 0.78-1.75, P = 0.46). No
      evidence of significant heterogeneity was detected for the two analyses (chi(2) =
      0.64, P = 0.89; I(2) = 0% and chi(2) = 2.44, P = 0.30; I(2) = 18%, respectively,
      for implant- and patient-based meta-analyses). CONCLUSION: There is little
      evidence that smoking is a risk factor for peri-implantitis. However, given the
      low number of included studies, future studies are needed to confirm these
      results.

PMID- 24438443
TI  - Recent advances in drug delivery systems for anti-diabetic drugs: a review.
AB  - Almost 200 million people worldwide are found to be affected by Diabetes mellitus
      (DM). DM is a metabolic disorder which occurs due to reduced insulin action
      and/or insulin secretion in the body. Reduced or inactive insulin results in
      imbalanced food metabolism. With the progression of disease, pathological changes
      like nephropathy, retinopathy and cardiovascular complications start occurring in
      the body. DM is mainly categorized into 2 types: type 1 DM and type 2 DM. Type 1
      is generally treated through insulin replacement therapy. Type 2 DM is treated
      with oral hypoglycemics. Oral hypoglycemics are classified into 5 types:
      sulfonylureas, biguanides, alpha-glucosidase inhibitors, meglitinide analogues
      and thiazolidinediones. Conventional dosage forms of most of these drugs bear
      some drawbacks such as frequent dosing, short half live, and low bioavailability.
      Therefore, to alleviate the drawbacks associated with conventional dosage forms,
      efforts have been made in the area of novel and controlled drug delivery system
      for oral hypoglycemics. Present review highlights various novel and controlled
      drug delivery systems that have been investigated by different researchers for
      achieving sustained and controlled drug delivery of oral hypoglycemics and for
      overcoming the limitations related with the conventional dosage forms of oral
      hypoglycemics. 

PMID- 24438444
TI  - Assessment of PLGA-PEG-PLGA copolymer hydrogel for sustained drug delivery in the
      ear.
AB  - Temperature sensitive copolymer systems were previously studied using modified
      diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA
      copolymer systems were found to provide sustained drug delivery for several days.
      The objectives of the present study were to assess the safety of PLGA-PEG-PLGA
      copolymers in intratympanic injection in guinea pigs in vivo and to determine the
      effects of additives glycerol and poloxamer in PLGA-PEGPLGA upon drug release in
      the diffusion cells in vitro for sustained inner ear drug delivery. In the
      experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated
      using auditory brainstem response (ABR). The effects of the additives upon drug
      release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz
      diffusion cells in vitro with cidofovir as the model drug. The phase transition
      temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives
      were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone
      did not affect hearing when delivered at 0.05-mL dose but caused hearing loss
      after 0.1-mL injection. In the drug release study, the incorporation of the
      bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to
      decrease the rate of drug release whereas the increase in the concentration of
      the humectant additive, glycerol, provided the opposite effect. In summary, the
      PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL
      dose and could provide sustained release that could be controlled by using the
      additives for inner ear applications. 

PMID- 24438445
TI  - High-resolution MRI findings in patients with capsular warning syndrome.
AB  - BACKGROUND: Capsular warning syndrome (CWS) is rare (1.5% of TIA presentations)
      but has a poor prognosis (7-day stroke risk of 60%). Up to date, the exact
      pathogenic mechanism of CWS has not been fully understood. We report the clinical
      presentations and high-resolution MRI (HR MRI) findings of two cases with
      capsular warning symptoms. CASE PRESENTATION: Case 1 was a 63-year-old man with a
      history of hypertension with recurrent episodes of left hemiparesis and
      dysarthria lasting 10 ~ 30 minutes. Case 2 was a 54-year-old woman with
      repetitive episodes of transient left hemiparesis and dysarthria lasting about 10
      minutes. Capsular infarctions on DWI were demonstrated in the territory of a
      lenticulostriate artery in both 2 patients. HR MRI disclosed atherosclerotic
      plaques on the ventral wall of the MCA where enticulostriate arteries were arisen
      from, although traditional digital subtraction angiography showed normal.
      Aggressive medical therapy with dual antithrombotic agents and statin was
      effective in these two cases. CONCLUSION: Our HR MRI data offer an insight into
      the pathophysiology of CWS which might be caused by atherosclerotic plaque in non
      stenotic MCA wall. HR MRI might be a useful modality for characterizing
      atherosclerotic plaques in the MCA and detecting the pathophysiology of the CWS.

PMID- 24438446
TI  - Hourly rounding: perspectives and perceptions of the frontline nursing staff.
AB  - AIMS: To gain knowledge of a nursing staff's perspectives and perceptions of
      hourly rounding in an acute care hospital setting. BACKGROUND: Research has shown
      hospitals that have successfully implemented hourly rounding have significant
      decreases in adverse patient events with improvements in patient and staff
      satisfaction. More recent studies and clinical observations by the author are
      revealing barriers and difficulties in translating this evidence-based practice
      to the bedside. METHOD: An original survey was distributed to direct care staff
      on six inpatient units. Descriptive analysis of each survey item and subanalysis
      of the registered nurse (n = 52) and patient care assistant (n = 15) responses
      was reported and aggregated according to demographic data and Rogers' Theory of
      Diffusion of Innovation. RESULTS: Findings varied considerably between job
      category, shift worked, unit worked on and educational level of the registered
      nurses. Overall only 25% (n = 13) of the registered nurses felt a sense of
      ownership of the hourly rounding initiative and only 23.1% (n = 12) agreed that
      completion of the hourly rounding paper documentation tool was a true indication
      that hourly rounding was actually being done. CONCLUSIONS AND IMPLICATIONS FOR
      NURSING MANAGEMENT: Results from this study may give nursing leadership and
      educators' insight on how to lead and sustain a new initiative or evidence-based
      practice.

PMID- 24438447
TI  - Comparison of baseline brachial artery measurements and effect on peak flow
      mediated dilation.
AB  - BACKGROUND: Flow-mediated dilation (FMD) following reactive hyperaemia can use
      different time-point measures for baseline diameter. The aim of this study is to
      compare preocclusion, occlusion and postocclusion baseline brachial artery
      measurements on the calculation of peak FMD. STUDY DESIGN: Ultrasound imaging of
      the brachial artery following reactive hyperaemia was conducted in 418 children
      and 533 adults. Baseline brachial artery measures were a 10-s average before
      (preocclusion), during (occlusion) and after (postocclusion) hyperaemia. Peak FMD
      was defined as the greatest percent change from baseline to the peak brachial
      artery diameter following reactive hyperaemia. RESULTS: Preocclusion, occlusion
      and postocclusion baseline measures of brachial artery diameter were not
      significantly different in children (3.15 +/- 0.51, 3.14 +/- 0.50 versus 3.11 +/-
      0.50 mm, P = 0.179) or adults (3.81 +/- 0.72, 3.81 +/- 0.73 versus 3.79 +/- 0.73
      mm, P = 0.201). Peak FMD values were not significantly different when calculated
      from preocclusion, occlusion or postocclusion baselines in children (6.77 +/-
      5.78, 6.93 +/- 4.03 versus 7.85 +/- 3.62%, P = 0.208) or adults (6.07 +/- 5.53,
      6.14 +/- 3.94 versus 6.62 +/- 3.70%, P = 0.266). CONCLUSION: We found no
      difference in FMD regardless of the baseline brachial artery diameter used in
      children and adults. Therefore, compilation of data and comparison of results
      from studies utilizing different measures of baseline brachial diameter may be
      able to be conducted.

PMID- 24438448
TI  - Brief screening questions for depression in chiropractic patients with low back
      pain: identification of potentially useful questions and test of their predictive
      capacity.
AB  - BACKGROUND: Depression is an important prognostic factor in low back pain (LBP)
      that appears to be infrequent in chiropractic populations. Identification of
      depression in few patients would consequently implicate screening of many. It is
      therefore desirable to have brief screening tools for depression. The objective
      of this study was to investigate if one or two items from the Major Depression
      Inventory (MDI) could be a reasonable substitute for the complete scale. METHODS:
      The MDI was completed by 925 patients consulting a chiropractor due to a new
      episode of LBP. Outcome measures were LBP intensity and activity limitation at 3
      months and 12-months follow-up. Single items on the MDI that correlated strongest
      and explained most variance in the total score were tested for associations with
      outcome. Finally, the predictive capacity was compared between the total scale
      and the items that showed the strongest associations with outcome measures.
      RESULTS: In this cohort 9% had signs of depression. The total MDI was
      significantly associated with outcome but explained very little of the variance
      in outcome. Four single items performed comparable to the total scale as
      prognostic factors. Items 1 and 3 explained the most variance in all outcome
      measures, and their predictive accuracies in terms of area under the curve were
      at least as high as for the categorised complete scale. CONCLUSIONS: Baseline
      depression measured by the MDI was associated with a worse outcome in
      chiropractic patients with LBP. A single item (no. 1 or 3) was a reasonable
      substitute for the entire scale when screening for depression as a prognostic
      factor.

PMID- 24438449
TI  - The prospective effects of workplace violence on physicians' job satisfaction and
      turnover intentions: the buffering effect of job control.
AB  - BACKGROUND: Health care professionals, including physicians, are at high risk of
      encountering workplace violence. At the same time physician turnover is an
      increasing problem that threatens the functioning of the health care sector
      worldwide. The present study examined the prospective associations of work
      related physical violence and bullying with physicians' turnover intentions and
      job satisfaction. In addition, we tested whether job control would modify these
      associations. METHODS: The present study was a 4-year longitudinal survey study,
      with data gathered in 2006 and 2010.The present sample included 1515 (61% women)
      Finnish physicians aged 25-63 years at baseline. Analyses of covariance (ANCOVA)
      were conducted while adjusting for gender, age, baseline levels, specialisation
      status, and employment sector. RESULTS: The results of covariance analyses showed
      that physical violence led to increased physician turnover intentions and that
      both bullying and physical violence led to reduced physician job satisfaction
      even after adjustments. We also found that opportunities for job control were
      able to alleviate the increase in turnover intentions resulting from bullying.
      CONCLUSIONS: Our results suggest that workplace violence is an extensive problem
      in the health care sector and may lead to increased turnover and job
      dissatisfaction. Thus, health care organisations should approach this problem
      through different means, for example, by giving health care employees more
      opportunities to control their own work.

PMID- 24438451
TI  - Campylobacter coli cultured from the stools of a patient with immunoproliferative
      small intestinal disease.
AB  - Campylobacter has been associated with immunoproliferative small intestinal
      disease (IPSID), on the basis of 16S rDNA sequencing, in situ hybridization, and
      immunohistochemistry. Here, for the first time, we have cultured Campylobacter
      from the stools of a patient with IPSID. Phenotypic analysis and whole genome
      sequencing identified Campylobacter coli. PCR on a IPSID tissue biopsy sample was
      positive for Campylobacter coli and negative for Campylobacter jejuni. These
      findings further support a causative role for Campylobacter in the development of
      IPSID.

PMID- 24438450
TI  - Comparison of different assembly and annotation tools on analysis of simulated
      viral metagenomic communities in the gut.
AB  - BACKGROUND: The main limitations in the analysis of viral metagenomes are perhaps
      the high genetic variability and the lack of information in extant databases. To
      address these issues, several bioinformatic tools have been specifically designed
      or adapted for metagenomics by improving read assembly and creating more
      sensitive methods for homology detection. This study compares the performance of
      different available assemblers and taxonomic annotation software using simulated
      viral-metagenomic data. RESULTS: We simulated two 454 viral metagenomes using
      genomes from NCBI's RefSeq database based on the list of actual viruses found in
      previously published metagenomes. Three different assembly strategies, spanning
      six assemblers, were tested for performance: overlap-layout-consensus algorithms
      Newbler, Celera and Minimo; de Bruijn graphs algorithms Velvet and MetaVelvet;
      and read probabilistic model Genovo. The performance of the assemblies was
      measured by the length of resulting contigs (using N50), the percentage of reads
      assembled and the overall accuracy when comparing against corresponding reference
      genomes. Additionally, the number of chimeras per contig and the lowest common
      ancestor were estimated in order to assess the effect of assembling on taxonomic
      and functional annotation. The functional classification of the reads was
      evaluated by counting the reads that correctly matched the functional data
      previously reported for the original genomes and calculating the number of over
      represented functional categories in chimeric contigs. The sensitivity and
      specificity of tBLASTx, PhymmBL and the k-mer frequencies were measured by
      accurate predictions when comparing simulated reads against the NCBI Virus
      genomes RefSeq database. CONCLUSIONS: Assembling improves functional annotation
      by increasing accurate assignations and decreasing ambiguous hits between viruses
      and bacteria. However, the success is limited by the chimeric contigs occurring
      at all taxonomic levels. The assembler and its parameters should be selected
      based on the focus of each study. Minimo's non-chimeric contigs and Genovo's long
      contigs excelled in taxonomy assignation and functional annotation,
      respectively.tBLASTx stood out as the best approach for taxonomic annotation for
      virus identification. PhymmBL proved useful in datasets in which no related
      sequences are present as it uses genomic features that may help identify distant
      taxa. The k-frequencies underperformed in all viral datasets.

PMID- 24438453
TI  - A review of phytochemistry, metabolite changes, and medicinal uses of the common
      food mung bean and its sprouts (Vigna radiata).
AB  - The seeds and sprouts of mung bean (Vigna radiata), a common food, contain
      abundant nutrients with biological activities. This review provides insight into
      the nutritional value of mung beans and its sprouts, discussing chemical
      constituents that have been isolated in the past few decades, such as flavonoids,
      phenolic acids, organic acids, amino acids, carbohydrates, and lipids. Moreover,
      we also summarize dynamic changes in metabolites during the sprouting process and
      related biological activities, including antioxidant, antimicrobial, anti
      inflammatory, antidiabetic, antihypertensive, lipid metabolism accommodation,
      antihypertensive, and antitumor effects, etc., with the goal of providing
      scientific evidence for better application of this commonly used food as a
      medicine. 

PMID- 24438454
TI  - Solastalgia: living with the environmental damage caused by natural disasters.
AB  - Forced separation from one's home may trigger emotional distress. People who
      remain in their homes may experience emotional distress due to living in a
      severely damaged environment. These people experience a type of 'homesickness'
      similar to nostalgia because the land around them no longer resembles the home
      they knew and loved. What they lack is solace or comfort from their home; they
      long for the home environment to be the way it was before. "Solastalgia" is a
      term created to describe feelings which arise in people when an environment
      changes so much that it negatively affects an individual's quality of life. Such
      changed environments may include drought-stricken areas and open-cut mines. The
      aim of this article is to describe how solastalgia, originally conceptualized as
      the result of man-made environmental change, can be similarly applied to the
      survivors of natural disasters. Using volcanic eruptions as a case example, the
      authors argue that people who experience a natural disaster are likely to suffer
      from solastalgia for a number of reasons, which may include the loss of housing,
      livestock and farmland, and the ongoing danger of living in a disaster-prone
      area. These losses and fears challenge people's established sense of place and
      identity and can lead to feelings of helplessness and depression.

PMID- 24438456
TI  - Who's hot and who's not: ocean warming alters species dominance through
      competitive displacement.
AB  - Species interactions have received little attention in climate-change studies,
      yet these interactions are fundamental to the functioning of ecosystems. Milazzo
      et al. (2013) combined field surveys and controlled experiments to show how
      increasing abundance of a range-extending species and ocean warming interactively
      affect the habitat occupancy of two co-occurring species with similar habitat
      preferences. The authors found that in warmer conditions the 'cool-water' species
      is competitively displaced from preferred algal habitat to sub-optimal seagrass
      habitat, but only at higher densities of the warm-water species. Their results
      provide an important first step for unravelling how simple species interactions
      can create novel communities.

PMID- 24438457
TI  - Desmoplastic trichoepithelioma with overlying pseudoepitheliomatous hyperplasia
      mimicking squamous cell carcinoma in a pediatric patient.

PMID- 24438455
TI  - Faster evolving Drosophila paralogs lose expression rate and ubiquity and
      accumulate more non-synonymous SNPs.
AB  - BACKGROUND: Duplicated genes can indefinately persist in genomes if either both
      copies retain the original function due to dosage benefit (gene conservation), or
      one of the copies assumes a novel function (neofunctionalization), or both copies
      become required to perform the function previously accomplished by a single copy
      (subfunctionalization), or through a combination of these mechanisms. Different
      models of duplication retention imply different predictions about substitution
      rates in the coding portion of paralogs and about asymmetry of these rates.
      RESULTS: We analyse sequence evolution asymmetry in paralogs present in 12
      Drosophila genomes using the nearest non-duplicated orthologous outgroup as a
      reference. Those paralogs present in D. melanogaster are analysed in conjunction
      with the asymmetry of expression rate and ubiquity and of segregating non
      synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions,
      on average, faster than their nearest singleton orthologs. The distribution of
      paralogs' substitution rate asymmetry is overdispersed relative to that of
      orthologous clades, containing disproportionally more unusually symmetric and
      unusually asymmetric clades. We show that paralogs are more asymmetric in: a)
      clades orthologous to highly constrained singleton genes; b) genes with high
      expression level; c) genes with ubiquitous expression and d) non-tandem
      duplications. We further demonstrate that, in each asymmetrically evolving pair
      of paralogs, the faster evolving member of the pair tends to have lower average
      expression rate, lower expression uniformity and higher frequency of non
      synonymous SNPs than its slower evolving counterpart. CONCLUSIONS: Our findings
      are consistent with the hypothesis that many duplications in Drosophila are
      retained despite stabilising selection being more relaxed in one of the paralogs
      than in the other, suggesting a widespread unfinished pseudogenization. This
      phenomenon is likely to make detection of neo- and subfunctionalization
      signatures difficult, as these models of duplication retention also predict
      asymmetries in substitution rates and expression profiles.

PMID- 24438458
TI  - Other causative factors for lung diseases in populations exposed to asbestos.

PMID- 24438459
TI  - The effects of zoledronic acid and dexamethasone on osseointegration of
      endosseous implants: histological and histomorphometrical evaluation in rats.
AB  - BACKGROUND: Bisphosphonates are a widely used class of drugs that prevent bone
      loss. Several side effects related to bisphosphonate therapy have been reported,
      including osteonecrosis of the jaws associated with invasive dental procedures
      and implants placement. OBJECTIVES: To evaluate the influence of intravenous
      nitrogen-containing BPs in combination with or without dexamethasone on
      osseointegration of titanium implants placed in an animal model. METHODS: Twenty
      seven male Wistar rats were divided into three groups: group 1 was treated solely
      with zoledronic acid, group 2 was treated with zoledronic acid and dexamethasone,
      and group 3 did only receive saline solution injections. Two endosseous implants
      were placed in each tibia, and three animals from each group were sacrificed at
      postoperative times of seven, 14, and 28 days. Non-decalcified sections were
      observed with light microscopy for histological and histomorphometrical analyses.
      RESULTS: Histomorphometrical analysis using the animals and the implants as unit
      of measurement revealed no statistically significant difference regarding bone
      implant contact and bone density among the three groups. Histological observation
      revealed that zoledronic acid-treated animals in combination with or without
      dexamethasone showed expressive less bone remodeling activity at 14 and 28 days
      after implants placement, compared with control specimens. CONCLUSIONS: The
      studied bisphosphonate regimens did not interfere with the osseointegration of
      the implants, cortical, or medular bone deposition, but a possible lack of bone
      remodeling of the original cortical bone may affect long-term osseointegration.

PMID- 24438460
TI  - Preventing substance misuse: study protocol for a randomised controlled trial of
      the Strengthening Families Programme 10-14 UK (SFP 10-14 UK).
AB  - BACKGROUND: Prevention of alcohol, drug and tobacco misuse by young people is a
      key public health priority. There is a need to develop the evidence base through
      rigorous evaluations of innovative approaches to substance misuse prevention. The
      Strengthening Families Programme 10-14 is a universal family-based alcohol, drugs
      and tobacco prevention programme, which has achieved promising results in US
      trials, and which now requires cross-cultural assessment. This paper therefore
      describes the protocol for a randomised controlled trial of the UK version of the
      Strengthening Families Programme 10-14 (SFP 10-14 UK). METHODS/DESIGN: The trial
      comprises a pragmatic cluster randomised controlled effectiveness trial with
      families as the unit of randomisation, with embedded process and economic
      evaluations. Participating families will be randomised to one of two treatment
      groups - usual care with full access to existing services (control group), or
      usual care plus SFP 10-14 UK (intervention group). The trial has two primary
      outcomes - the number of occasions that young people report having drunk alcohol
      in the last 30 days, and drunkenness during the last 30 days, both dichotomised
      as 'never' and '1-2 times or more'. The main follow-up is at 2 years past
      baseline, and short-term and intermediate outcomes are also measured at 9 and 15
      months. DISCUSSION: The results from this trial will provide evidence on the
      effectiveness and cost-effectiveness of an innovative universal family-based
      substance misuse prevention programme in a UK context. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN63550893.

PMID- 24438462
TI  - Transient renal enlargement in pediatric hematopoietic cell transplant
      recipients.
AB  - Age-dependent renal length tables are routinely used when interpreting pediatric
      ultrasound. Standard renal length tables may not be accurate for HCT patients due
      to treatment effects on kidney size. The purpose of this study was to determine
      whether renal size changes from expected lengths based on age after HCT in the
      absence of other markers of renal disease. Four hundred and fifty renal
      measurements were made on 101 patients who underwent HCT between 2006 and 2010.
      Renal length was measured at 1-90 days pre-HCT and at 0-30, 31-90, 91-180, and
      181+ days post-HCT. Values were compared with normal renal length tables. Average
      post-HCT renal lengths were greater than established normative renal length data
      within every age group. Age-adjusted average renal lengths measured at 0-30 and
      31-90 days post-transplantation were significantly larger than pre-HCT renal
      lengths, with relative increases of 6.9% (4.5, 9.4; p < 0.001) and 3.9% (1.4,
      6.4; p = 0.003), respectively. Average renal length did not differ significantly
      after 90 days post-transplantation. HCT patients may have larger kidneys in the
      absence of renal disease. Awareness of the potential phenomenon of transient
      renal enlargement following HCT can prevent misdiagnosis and eliminate
      unnecessary diagnostic evaluations, interventions, anxiety, resource allocation,
      and financial costs.

PMID- 24438461
TI  - Norwegian survival prediction model in trauma: modelling effects of anatomic
      injury, acute physiology, age, and co-morbidity.
AB  - INTRODUCTION: Anatomic injury, physiological derangement, age, and injury
      mechanism are well-founded predictors of trauma outcome. We aimed to develop and
      validate the first Scandinavian survival prediction model for trauma. METHODS:
      Eligible were patients admitted to Oslo University Hospital Ulleval within 24 h
      after injury with Injury Severity Score >= 10, proximal penetrating injuries or
      received by a trauma team. The derivation dataset comprised 5363 patients (August
      2000 to July 2006); the validation dataset comprised 2517 patients (August 2006
      to July 2008). Exclusion because of missing data was < 1%. Outcome was 30-day
      mortality. Logistic regression analysis incorporated fractional polynomial
      modelling and interaction effects. Model validation included a calibration plot,
      Hosmer-Lemeshow test and receiver operating characteristic (ROC) curves. RESULTS:
      The new survival prediction model included the anatomic New Injury Severity Score
      (NISS), Triage Revised Trauma Score (T-RTS, comprising Glascow Coma Scale score,
      respiratory rate, and systolic blood pressure), age, pre-injury co-morbidity
      scored according to the American Society of Anesthesiologists Physical Status
      Classification System (ASA-PS), and an interaction term. Fractional polynomial
      analysis supported treating NISS and T-RTS as linear functions and age as cubic.
      Model discrimination between survivors and non-survivors was excellent. Area (95%
      confidence interval) under the ROC curve was 0.966 (0.959-0.972) in the
      derivation and 0.946 (0.930-0.962) in the validation dataset. Overall, low
      mortality and skewed survival probability distribution invalidated model
      calibration using the Hosmer-Lemeshow test. CONCLUSIONS: The Norwegian survival
      prediction model in trauma (NORMIT) is a promising alternative to existing
      prediction models. External validation of the model in other trauma populations
      is warranted.

PMID- 24438464
TI  - Polyethylene bag wrapping to prevent hypothermia during percutaneous central
      venous catheter insertion in the preterm newborn under 32 weeks of gestation.
AB  - AIM: In preterm neonates, during nursing procedures, body temperature decreases.
      This study evaluates the interest of polyethylene bag wrapping to prevent this
      decrease during percutaneous central venous catheter (PCVC) insertion procedure,
      in preterm neonates under 32 weeks of gestation nursed in closed incubators.
      METHODS: This prospective observational study compared two periods: [May 2009
      September 2009]: "without polyethylene bag wrapping" and [October 2009-March
      2010]: "with polyethylene bag wrapping". The main criterion was newborn skin
      temperature at the end of the procedure. RESULTS: There was no difference between
      the two groups for skin temperature before the procedure (36.9 +/- 0.3  degrees C
      versus 36.9 +/- 0.3  degrees C; p = NS). The skin temperature at the end of the
      procedure was lower in the "without bag wrapping" group (36.0 +/- 0.5  degrees C)
      compared to the "bag wrapping" group (36.4 C +/- 0.5  degrees C; p = 0.01).
      Furthermore, no skin temperature at the end was higher than 37.4  degrees C in
      the bag wrapping group. CONCLUSION: The use of a polyethylene bag was effective
      in decreasing skin temperature fall during a PCVC insertion procedure in our
      population. No side effects were observed. The benefit of prolonged wrapping or
      for shorter procedure should be evaluated.

PMID- 24438465
TI  - For love or money: registered nurses who return to hospital practice.
AB  - AIM: This commentary explores the value that returning nurses bring to the
      hospital setting. BACKGROUND: Nurses who have left hospital practice, usually due
      to family obligations, often return once the children are older. They return
      because they love nursing or they need to make money. They are at a point in
      their lives where they want to make a difference and miss the nurse-patient
      relationship. During recessions, nurses return to hospital practice because
      recessions tend to affect male dominated occupations. EVALUATION: Research and
      policy literature on the returning and/or older nurse was reviewed with a focus
      on the benefits and challenges of having returning nurses in hospital practice.
      KEY ISSUES: Returning nurses serve as role models to younger nurses. They also
      bring experiential knowledge to patient situations. CONCLUSION: There is limited
      research on this group of nurses. Yet they are ready for reentry in short order
      during nursing shortages. When they return, they add value to the hospital unit.
      IMPLICATIONS FOR NURSING MANAGEMENT: Returning nurses want shorter workdays,
      alternative roles, and less physically taxing work. This can be achieved by
      offering flexible scheduling and work hours, creating niche roles and providing a
      more worker friendly physical environment.

PMID- 24438466
TI  - MicroRNA-34a: role in cancer and cardiovascular disease.
AB  - Small non-coding microRNAs (miRNAs) regulate gene expression at the post
      transcriptional and translational levels. The dysregulated miRNAs are involved in
      a large variety of diseases including cancer and cardiovascular diseases. MiR-34a
      is one of the most anti-oncomiRs that is down-regulated in multiple types of
      cancer. It regulates a wide range of genes and pathways involved in cancer
      initiation, progression and metastasis. Next to cancer, miR-34a is recently found
      to be implicated in cardiovascular disease as one damager factor. In this review,
      we highlight the complex roles of miR-34a in cancer and cardiovascular disease,
      as well as the therapeutic potentials. 

PMID- 24438467
TI  - Session rating of perceived exertion following resistance exercise with blood
      flow restriction.
AB  - Session ratings of perceived exertion (SRPE) provide a valid and reliable
      indicator of resistance exercise session intensity. However, there is a lack of
      studies on the effects of resistance exercise with blood flow restriction (BFR)
      on SRPE. Thus, the aim of this study is to compare the effects of resistance
      exercise at high intensity versus low intensity with BFR on internal training
      load measured by SRPE. Thirteen young (22.2 +/- 3.8 years) resistance-trained men
      (training experience 3.2 +/- 2.4 years) participated in the study protocol. After
      determining one maximum repetition (1-RM), the subjects were assigned to two
      groups in a counterbalanced design (i) high-intensity exercise (HIE, performed
      one training session at 80% of 1-RM) and (ii) low intensity with BFR (BFR,
      performed an exercise session at 50% of 1-RM with BFR). During each session,
      subjects performed three sets of unilateral elbow flexion leading to concentric
      failure with a 1-min rest interval between sets. A cuff around the arm, inflated
      at 110 mmHg, was used continuously for BFR. The SRPE was reported 30 min after
      the end of the session. The low intensity with BFR showed lower total work
      (197.13 +/- 63.49 versus 300.92 +/- 71.81 kg; P = 0.002) and higher SRPE (9
      versus 6; P = 0.007) than high-intensity resistance exercise. The present results
      indicate that BFR is an important factor to increase internal training load.
      Future studies should investigate the physiological stress imposed by different
      training methods rather than just quantify the external training load such as
      intensity or volume.

PMID- 24438468
TI  - The association between pain diagram area, fear-avoidance beliefs, and pain
      catastrophising.
AB  - BACKGROUND: The development of clinical practice guidelines for managing spinal
      pain have been informed by a biopsychosocial framework which acknowledges that
      pain arises from a combination of psychosocial and biomechanical factors. There
      is an extensive body of evidence that has associated various psychosocial factors
      with an increased risk of experiencing persistent pain. Clinicians require
      instruments that are brief, easy to administer and score, and capable of validly
      identifying psychosocial factors. The pain diagram is potentially such an
      instrument. The aim of our study was to examine the association between pain
      diagram area and psychosocial factors. METHODS: 183 adults, aged 20-85, with
      spinal pain were recruited. We administered a demographic checklist; pain
      diagram; 11-point Numerical Rating Scale assessing pain intensity; Pain
      Catastrophising Scale (PCS); MOS 36 Item Short Form Health Survey (SF-36); and
      the Fear Avoidance Beliefs Questionnaire (FABQ). Open source software, GIMP, was
      used to calculate the total pixilation area on each pain diagram. Linear
      regression was used to examine the relationship between pain diagram area and the
      following variables: age; gender; pain intensity; PCS total score; FABQ-Work
      scale score; FABQ-Activity scale score; and SF-36 Mental Health scale score.
      RESULTS: There were no significant associations between pain diagram area and any
      of the clinical variables. CONCLUSION: Our findings showed that that pain diagram
      area was not a valid measure to identify psychosocial factors. Several
      limitations constrained our results and further studies are warranted to
      establish if pain diagram area can be used assess psychosocial factors.

PMID- 24438470
TI  - Living donor parathyroid allotransplantation with robotic transaxillary
      procurement in a kidney transplant recipient.

PMID- 24438469
TI  - Birth setting, transfer and maternal sense of control: results from the DELIVER
      study.
AB  - BACKGROUND: In the Netherlands, low risk women receive midwife-led care and can
      choose to give birth at home or in hospital. There is concern that transfer of
      care during labour from midwife-led care to an obstetrician-led unit leads to
      negative birth experiences, in particular among those with planned home birth. In
      this study we compared sense of control, which is a major attribute of the
      childbirth experience, for women planning home compared to women planning
      hospital birth under midwife-led care. In particular, we studied sense of control
      among women who were transferred to obstetric-led care during labour according to
      planned place of birth: home versus hospital. METHODS: We used data from the
      prospective multicentre DELIVER (Data EersteLIjns VERloskunde) cohort-study,
      conducted in 2009 and 2010 in the Netherlands. Sense of control during labour was
      assessed 6 weeks after birth, using the short version of the Labour Agentry Scale
      (LAS-11). A higher LAS-11 score indicates a higher feeling of control. We
      considered a difference of a minimum of 5.5 points as clinically relevant.
      RESULTS: Nulliparous- and parous women who planned a home birth had a 2.6 (95% CI
      1.0, 4.3) and a 3.0 (1.6, 4.4) higher LAS score during first stage of labour
      respectively and during second stage a higher score of 2.8 (0.9, 4.7) and 2.3
      (0.6, 4.0), compared with women who planned a hospital birth. Overall, women who
      were transferred experienced a lower sense of control than women who were not
      transferred. Parous women who planned a home birth and who were transferred had a
      4.3 (0.2, 8.4) higher LAS score in 2nd stage, compared to those who planned a
      hospital birth and who were transferred. CONCLUSION: We found no clinically
      relevant differences in feelings of control among women who planned a home or
      hospital birth. Transfer of care during labour lowered feelings of control, but
      feelings of control were similar for transferred women who planned a home or
      hospital birth.As far as their expected sense of control is concerned, low risk
      women should be encouraged to give birth at the location of their preference.

PMID- 24438471
TI  - Articulating current service development practices: a qualitative analysis of
      eleven mental health projects.
AB  - BACKGROUND: The utilisation of good design practices in the development of
      complex health services is essential to improving quality. Healthcare
      organisations, however, are often seriously out of step with modern design
      thinking and practice. As a starting point to encourage the uptake of good design
      practices, it is important to understand the context of their intended use. This
      study aims to do that by articulating current health service development
      practices. METHODS: Eleven service development projects carried out in a large
      mental health service were investigated through in-depth interviews with six
      operation managers. The critical decision method in conjunction with diagrammatic
      elicitation was used to capture descriptions of these projects. Stage-gate design
      models were then formed to visually articulate, classify and characterise
      different service development practices. RESULTS: Projects were grouped into
      three categories according to design process patterns: new service introduction
      and service integration; service improvement; service closure. Three common
      design stages: problem exploration, idea generation and solution evaluation -
      were then compared across the design process patterns. Consistent across projects
      were a top-down, policy-driven approach to exploration, underexploited idea
      generation and implementation-based evaluation. CONCLUSIONS: This study provides
      insight into where and how good design practices can contribute to the
      improvement of current service development practices. Specifically, the following
      suggestions for future service development practices are made: genuine user needs
      analysis for exploration; divergent thinking and innovative culture for idea
      generation; and fail-safe evaluation prior to implementation. Better training for
      managers through partnership working with design experts and researchers could be
      beneficial.

PMID- 24438472
TI  - Granulomatous syringotropic mycosis fungoides with two lesions having reactive B
      cell proliferation.
AB  - Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. The
      diagnosis of MF may occasionally be challenging, particularly for variants of MF
      such as folliculotropic MF, syringotropic MF and granulomatous MF. Herein, we
      describe a case of MF in which syringotropism and a prominent granulomatous
      reaction were noted around the affected eccrine gland. This case represents a
      rare example of MF with multiple unusual histopathological features, including
      syringotropism, a granulomatous reaction and a reactive B-cell proliferation. 

PMID- 24438473
TI  - Assessing antibiotic sorption in soil: a literature review and new case studies
      on sulfonamides and macrolides.
AB  - The increased use of veterinary antibiotics in modern agriculture for therapeutic
      uses and growth promotion has raised concern regarding the environmental impacts
      of antibiotic residues in soil and water. The mobility and transport of
      antibiotics in the environment depends on their sorption behavior, which is
      typically predicted by extrapolating from an experimentally determined soil-water
      distribution coefficient (Kd). Accurate determination of Kd values is important
      in order to better predict the environmental fate of antibiotics. In this paper,
      we examine different analytical approaches in assessing Kd of two major classes
      of veterinary antibiotics (sulfonamides and macrolides) and compare the existing
      literature data with experimental data obtained in our laboratory. While
      environmental parameters such as soil pH and organic matter content are the most
      significant factors that affect the sorption of antibiotics in soil, it is
      important to consider the concentrations used, the analytical method employed,
      and the transformations that can occur when determining Kd values. Application of
      solid phase extraction and liquid chromatography/mass spectrometry can facilitate
      accurate determination of Kd at environmentally relevant concentrations. Because
      the bioavailability of antibiotics in soil depends on their sorption behavior, it
      is important to examine current practices in assessing their mobility in soil. 

PMID- 24438475
TI  - Ultrasound and fine-needle aspiration in dermatology, underuse of minimally
      invasive, efficient diagnostic tools.
AB  - BACKGROUND: Ultrasound imaging and ultrasound-guided fine-needle aspiration (FNA)
      are common procedures used to evaluate and sample cutaneous and subcutaneous
      tissue. Although ultrasound and FNA have been explored for individual neoplasms,
      lymph node involvement, and metastases, their use in day-to-day dermatology is
      not well defined. OBJECTIVE: To investigate the use and utility of ultrasound and
      FNA in the dermatologic surgery division of a large academic institution.
      METHODS: Retrospective case review of all ultrasound and FNA procedures ordered
      by a dermatologic surgeon over a 3-year period. RESULTS: Metastatic disease was
      suspected in 11 of 21 (52.4%) cases. Cytology confirmed the presence of
      metastatic disease in two of the 11 cases, and metastatic disease was identified
      in one additional case in which the diagnosis was not suspected at clinical
      presentation. Cytology revealed leukemia or lymphoma in three (14.3%) cases, two
      of which were new diagnoses. Sonographic imaging and cytology revealed a benign
      diagnosis in 16 (76.2%) cases, five of which were reactive lymph nodes.
      CONCLUSIONS: The results suggest that ultrasound and FNA are underused techniques
      that may play an important role in dermatology diagnostics and have the potential
      for expansion in day-to-day clinical practice.

PMID- 24438474
TI  - Comparative genomic analysis reveals distinct genotypic features of the emerging
      pathogen Haemophilus influenzae type f.
AB  - BACKGROUND: The incidence of invasive disease caused by encapsulated Haemophilus
      influenzae type f (Hif) has increased in the post-H. influenzae type b (Hib)
      vaccine era. We previously annotated the first complete Hif genome from a
      clinical isolate (KR494) that caused septic shock and necrotizing myositis. Here,
      the full genome of Hif KR494 was compared to sequenced reference strains Hib
      10810, capsule type d (Hid) Rd Kw20, and finally nontypeable H. influenzae 3655.
      The goal was to identify possible genomic characteristics that may shed light
      upon the pathogenesis of Hif. RESULTS: The Hif KR494 genome exhibited large
      regions of synteny with other H. influenzae, but also distinct genome
      rearrangements. A predicted Hif core genome of 1390 genes was shared with the
      reference strains, and 6 unique genomic regions comprising half of the 191 unique
      coding sequences were revealed. The majority of these regions were inserted
      genetic fragments, most likely derived from the closely-related Haemophilus spp.
      including H. aegyptius, H. haemolyticus and H. parainfluenzae. Importantly, the
      KR494 genome possessed several putative virulence genes that were distinct from
      non-type f strains. These included the sap2 operon, aef3 fimbriae, and genes for
      kanamycin nucleotidyltranserase, iron-utilization proteins, and putative YadA
      like trimeric autotransporters that may increase the bacterial virulence.
      Furthermore, Hif KR494 lacked a hisABCDEFGH operon for de novo histidine
      biosynthesis, hmg locus for lipooligosaccharide biosynthesis and biofilm
      formation, the Haemophilus antibiotic resistance island and a Haemophilus
      secondary molybdate transport system. We confirmed the histidine auxotrophy and
      kanamycin resistance in Hif by functional experiments. Moreover, the pattern of
      unique or missing genes of Hif KR494 was similar in 20 Hif clinical isolates
      obtained from different years and geographical areas. A cross-species comparison
      revealed that the Hif genome shared more characteristics with H. aegyptius than
      Hid and NTHi. CONCLUSIONS: The genomic comparative analyses facilitated
      identification of genotypic characteristics that may be related to the specific
      virulence of Hif. In relation to non-type f H. influenzae strains, the Hif genome
      contains differences in components involved in metabolism and survival that may
      contribute to its invasiveness.

PMID- 24438476
TI  - Deformation thresholds for chondrocyte death and the protective effect of the
      pericellular matrix.
AB  - In cartilage tissue engineering studies, the stimulatory effect of mechanical
      perturbation declines after the first 2 weeks of culture. Similarly, it is known
      that chondrocyte-agarose constructs should not be loaded within the first days
      after seeding, to prevent considerable cell death, suggesting a mechanical
      threshold. This study aims to establish a relationship between chondrocyte
      deformation and death, and to evaluate the protective effect of the pericellular
      matrix (PCM) that is formed in 3D cultures. Chondrocyte viability was monitored
      every hour for 24 h after applying a strain range of 0% to 25% to agarose
      constructs containing chondrocytes, cultured for 1, 3, 5, 7, or 10 days. At these
      culture time points, the PCM thickness and chondrocyte deformation were assessed
      by means of histology and assayed for biochemical contents. Inverse finite
      element (FE) simulations were used to evaluate the change of mechanical
      properties of the chondrocyte and PCM over the 10-day culture duration.
      Chondrocyte death was demonstrated to be dependent on both the magnitude and
      duration of straining. The highest cell death was observed at day 1 (43%),
      reducing over culture duration (15% at day 3 and 2.5% at day 10). Cell
      deformation at 25% compression decreased significantly over culture duration
      (aspect ratio of 2.24+/-0.67 at day 1 and 1.45+/-0.24 at day 3) and with
      increased matrix production. Inverse FE simulations showed an increasing PCM
      Young's modulus of 45 kPa at day 3 to 162 kPa at day 10. The current results
      provide evidence for a mechanical threshold for chondrocyte death and for the
      protective effect of the PCM. As such, these insights may help in establishing
      mechanical loading protocols for cartilage tissue engineering studies. 

PMID- 24438477
TI  - Corneal epithelial cell viability of an ex vivo porcine eye model.
AB  - PURPOSE: The aim was to assess the consistency of corneal epithelial cell
      viability of an ex vivo porcine eye model. METHOD: Six porcine eye models (four
      test and two control) were prepared for each experiment. The model has a computer
      controlled mechanical arm, which could move the eyelid of the porcine eye and
      apply phosphate buffered saline to simulate blinking and lacrimation. The four
      test eyes were set up to simulate evaporative dry eyes with simulated lacrimation
      and blinking (one blink and one drop of buffered saline per minute) over three
      hours. Control A models were set up to collect pre-experimental baseline data,
      while those of control B were the same as the test eyes but without lacrimation
      and blinking simulation. All porcine eyes were kept in a closed chamber with
      temperature and humidity well controlled. After three hours, the cells of all
      eyes (except control A, which were assessed immediately before commencement of
      the experiment) were assessed. The eyes were first dipped into 0.4 per cent
      trypan blue solution. Following the dissection and separation of the cells, the
      number of dead cells were then counted under the microscope with a field size of
      0.25 mm(2). The experiment was repeated 11 times. RESULTS: No significant
      differences were found in the number of dead cells among the four test eyes in
      both the central and peripheral cornea. There were significantly more dead cells
      in the test eyes compared to control A but significantly less when compared to
      control B. More dead cells were found in the central cornea than the peripheral
      cornea in the test eyes but the difference was not observed in controls A and B.
      CONCLUSION: Epithelial cell viabilities among the four porcine eye models with
      simulated lacrimation and blinking were consistent. The majority of cells were
      viable before the experiment and simulated lacrimation and blinking maintained
      more viable cells over time.

PMID- 24438479
TI  - Initial data on recollections of pathways to inflated responsibility beliefs in
      patients with obsessive-compulsive disorder.
AB  - BACKGROUND: Despite literature establishing a relationship between maladaptive
      beliefs and symptoms of obsessive-compulsive disorder (OCD), there are few
      studies addressing how these beliefs develop. Salkovskis and colleagues (1999)
      proposed specific domains of childhood experiences leading to heightened beliefs
      regarding responsibility. Prior studies in students and individuals who just
      completed treatment for OCD have found support for this theory. However, we are
      not aware of published data from individuals with current OCD. AIMS: This paper
      presents initial data from adults currently meeting criteria for OCD as well as
      both anxious and non-anxious controls. METHOD: Recollections of childhood
      experiences, current OCD-related beliefs, and OCD symptoms were assessed using
      self-report measures in 39 individuals seeking treatment for OCD, 36 anxious
      controls and 39 healthy controls. RESULTS: Initial data suggested that in
      individuals with OCD, increased reports of childhood exposure to overprotection
      and experiences where one's actions caused or influenced misfortune were
      associated with stronger OCD-related beliefs. Further, compared to community
      controls, individuals with OCD reported more childhood experiences where one's
      actions caused or influenced misfortune, though they did not differ from anxious
      controls in childhood responsibility experiences. CONCLUSIONS: These initial
      findings provide minimal support for the proposed model of the development of
      inflated responsibility beliefs, and highlight the need for research examining
      the etiology of OCD related beliefs with updated models, larger samples, and
      ultimately using prospective methods.

PMID- 24438478
TI  - Screening uptake rates and the clinical and cost effectiveness of screening for
      gestational diabetes mellitus in primary versus secondary care: study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: The risks associated with gestational diabetes mellitus (GDM) are
      well recognized, and there is increasing evidence to support treatment of the
      condition. However, clear guidance on the ideal approach to screening for GDM is
      lacking. Professional groups continue to debate whether selective screening
      (based on risk factors) or universal screening is the most appropriate approach.
      Additionally, there is ongoing debate about what levels of glucose abnormalities
      during pregnancy respond best to treatment and which maternal and neonatal
      outcomes benefit most from treatment. Furthermore, the implications of possible
      screening options on health care costs are not well established. In response to
      this uncertainty there have been repeated calls for well-designed, randomised
      trials to determine the efficacy of screening, diagnosis, and management plans
      for GDM. We describe a randomised controlled trial to investigate screening
      uptake rates and the clinical and cost effectiveness of screening in primary
      versus secondary care settings. METHODS/DESIGN: This will be an unblinded, two
      group, parallel randomised controlled trial (RCT). The target population includes
      784 women presenting for their first antenatal visit at 12 to 18 weeks gestation
      at two hospitals in the west of Ireland: Galway University Hospital and Mayo
      General Hospital. Participants will be offered universal screening for GDM at 24
      to 28 weeks gestation in either primary care (n=392) or secondary care (n=392)
      locations. The primary outcome variable is the uptake rate of screening.
      Secondary outcomes include indicators of clinical effectiveness of screening at
      each screening site (primary and secondary) including gestational week at time of
      screening, time to access antenatal diabetes services for women diagnosed with
      GDM, and pregnancy and neonatal outcomes for women with GDM. In addition,
      parallel economic and qualitative evaluations will be conducted. The trial will
      cover the period from the woman's first hospital antenatal visit at 12 to 18
      weeks gestation, until the completion of the pregnancy. TRIAL REGISTRATION:
      Current Controlled Trials: ISRCTN02232125.

PMID- 24438480
TI  - Anatomy of a population cycle: the role of density dependence and demographic
      variability on numerical instability and periodicity.
AB  - Determining the causes of cyclic fluctuations in population size is a central
      tenet in population ecology and provides insights into population regulatory
      mechanisms. We have a firm understanding of how direct and delayed density
      dependence affects population stability and cyclic dynamics, but there remains
      considerable uncertainty in the specific processes contributing to demographic
      variability and consequent change in cyclic propensity. Spatiotemporal
      variability in cyclic propensity, including recent attenuation or loss of
      cyclicity among several temperate populations and the implications of habitat
      fragmentation and climate change on this pattern, highlights the heightened need
      to understand processes underlying cyclic variation. Because these stressors can
      differentially impact survival and productivity and thereby impose variable time
      delays in density dependence, there is a specific need to elucidate how
      demographic vital rates interact with the type and action of density dependence
      to contribute to population stability and cyclic variation. Here, we address this
      knowledge gap by comparing the stability of time series derived from general and
      species-specific (Canada lynx: Lynx canadensis; small rodents: Microtus, Lemmus
      and Clethrionomys spp.) matrix population models, which vary in their demographic
      rates and the direct action of density dependence. Our results reveal that
      density dependence acting exclusively on survival as opposed to productivity is
      destabilizing, suggesting that a shift in the action of population regulation
      toward reproductive output may decrease cyclic propensity and cycle amplitude.
      This result was the same whether delayed density dependence was pulsatile and
      acted on a single time period (e.g. t-1, t-2 or t-3) vs. more constant by
      affecting a successive range of years (e.g. t-1,..., t-3). Consistent with our
      general models, reductions in reproductive potential in both the lynx and small
      rodent systems led to notably large drops in cyclic propensity and amplitude,
      suggesting that changes in this vital rate may contribute to the spatial or
      temporal variability observed in the cyclic dynamics of both systems.
      Collectively, our results reveal that the type of density dependence and its
      effect on different demographic parameters can profoundly influence numeric
      stability and cyclic propensity and therefore may shift populations across the
      cyclic-to-noncyclic boundary. 

PMID- 24438481
TI  - Immunohistochemical analysis of blood vessels in peri-implant mucosa: a
      comparison between mini-incision flapless and flap surgeries in domestic pigs.
AB  - AIM: The aim of this experimental study is to compare the effect of mini-incision
      flapless versus flap technique of implant placement on the amount of vascular
      structures and blood vessel elements in peri-implant soft tissue, using
      immunohistochemical analysis. METHOD: The experiment was conducted on five
      domestic pigs. Each animal received six implants in mandible according to the
      split-mouth design. On one randomly chosen jaw side, mini-incision flapless
      surgery was performed, whereas on the opposite jaw side, flap was raised. After 3
      months of implant healing through submerged approach, the experimental animals
      were sacrificed and samples for immunohistochemical analyses were taken from the
      buccal side of peri-implant mucosa next to the neck of implants, from three
      levels. The study outcome was the presence of vascular structures and elements of
      the blood vessels in the peri-implant mucosa per microscopic field, estimated
      through ordinal scores from 0 to 2. Effects of surgical approach, site of
      implantation, and their interaction on vascular scores of peri-implant mucosa
      were assessed by Brunner and Langer nonparametric analysis of longitudinal data.
      RESULTS: Statistically significant effect of surgical approach on vascularity of
      peri-implant mucosa has been revealed in the second mucosal layer, where flapless
      approach provided higher vascularity compared with flap approach (P = 0.002). In
      the remaining two layers, surgical approach did not affect mucosal vascularity
      significantly (layer 1: P = 0.071; layer 3: P = 0.433). CONCLUSION: The flapless
      surgical implant placement approach using mini-incision provides better
      vascularization of peri-implant mucosa after 3 months of healing compared with
      flap surgery.

PMID- 24438482
TI  - Varicella zoster reactivation after hematopoietic stem cell transplant in
      children is strongly correlated with leukemia treatment and suppression of host T
      lymphocyte immunity.
AB  - BACKGROUND AND AIMS: Varicella zoster virus (VZV) reactivation following
      hematopoietic stem cell transplantation (HSCT) may cause significant morbidity
      and mortality. We undertook a retrospective study to determine the frequency and
      risk factors associated with VZV reactivation, including underlying disease, the
      use of fludarabine in high-risk leukemia chemotherapy protocols, and immune
      status before HSCT. PATIENTS AND METHODS: We studied 163 children who underwent a
      first HSCT between 2002 and 2008, before introduction of routine VZV prophylaxis
      on our unit. VZV diagnosis was based on clinical features and supported by
      polymerase chain reaction on plasma and/or vesical fluid. Patient data and
      possible risk factors pre- and post HSCT were recorded and compared using a
      multivariate regression analysis. RESULTS: Within this cohort, 41 (25%) patients
      developed VZV reactivation during the first year after transplantation at a
      median of 60 days post HSCT. VZV reactivation occurred more often within the
      subgroup of patients with acute leukemia compared with the remainder of patients
      (38% vs. 15%, P < 0.01). Multivariate Cox regression analysis revealed that,
      besides positive VZV serology in patients pre-HSCT (P = 0.03), acute leukemia as
      the indication for HSCT remained the only independent risk factor for VZV
      reactivation (P = 0.025, odds ratio 2.5, 95% confidence interval 1.1-5.6). This
      was associated with low pre-transplant T-cell counts, especially in the CD4(+)
      subset. No differences were found in relation to donor type, age, or use of
      serotherapy. CONCLUSION: VZV reactivation after HSCT predominates in acute
      leukemia patients and is associated with low T CD4(+) lymphocyte counts. This
      finding demonstrates the impact of pre-HSCT host immune suppression on VZV
      reactivation patterns after HSCT.

PMID- 24438483
TI  - Pre-treatment of bupivacaine-induced cardiovascular depression using different
      lipid formulations of propofol.
AB  - BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal
      doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine
      induced cardiotoxicity. The aim of this study is to investigate the effects of
      propofol in intralipid or medialipid emulsions on bupivacaine-induced
      cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5
      mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or
      saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was
      infused. We recorded time to first dysrhythmia occurrence, respective times to
      25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time
      to asystole and total amount of bupivacaine consumption. Blood and tissue samples
      were collected following asystole. RESULTS: The time to first dysrhythmia
      occurrence, time to 25% and 50% reductions in HR, and time to asystole were
      longer in Group P than the other groups. The cumulative bupivacaine dose given at
      those time points was higher in Group P. Plasma bupivacaine levels were
      significantly lower in Group P than in Group C. Bupivacaine levels in the brain
      and heart were significantly lower in Group P and Group L than in Group C.
      CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared
      with propofol in medialipid or saline, delayed the onset of bupivacaine-induced
      cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies
      are needed to explore tissue bupivacaine levels of propofol in medialipid and
      adapt these results to clinical practice.

PMID- 24438484
TI  - Intimate partner violence among women with mental health-related activity
      limitations: a Canadian population based study.
AB  - BACKGROUND: There is strong evidence that women with serious or chronic mental
      illness experience higher rates of violence than women in the general population.
      Our objective was to examine the risk of intimate partner violence (IPV), a form
      of violence that is often recurrent and linked to negative physical and
      psychological consequences, among a representative sample of non
      institutionalized women with activity limitations (ALs) due to a mental health
      condition. METHODS: Data from the 2009 General Social Survey were used, a
      national, population-based, cross-sectional survey. The sample included 6851
      women reporting contact with a current or former partner in the previous five
      years, of whom 322 (4.7%) reported a mental health-related AL always/often or
      sometimes. RESULTS: The prevalence of any type of IPV was highest among women
      with mental health-related ALs always/often (54.4%), followed by women reporting
      ALs sometimes (49.9%), and those reporting no ALs (18.3%, p < 0.0001). The same
      pattern was observed for emotional (51.1%, 45.5%, 16.3%, p < 0.0001) and
      financial IPV (18.1%, 9.5%, 4.0%, p < 0.0001). For physical/sexual violence,
      rates were similar among women reporting mental health-related ALs always/often
      and sometimes, but were lower among those reporting no ALs (20.2%, 20.9%, 5.9%, p
      < 0.0001). In a logistic regression analysis the odds of having experienced any
      IPV remained greater for women reporting ALs always/often (OR = 3.65; 95% CI:
      2.10, 6.32) and sometimes (OR = 3.20; 95% CI: 2.15, 4.75) than those reporting no
      ALs. Several social capital variables, including perceptions of having
      experienced discrimination, a weak sense of belonging in their local community,
      and low trust toward family members and strangers were also significantly
      associated with having experienced IPV. CONCLUSION: Findings suggest that women
      with mental health-related ALs may be at increased risk of IPV. Health and social
      service providers may need, therefore, to better target prevention and
      intervention initiatives to this population.

PMID- 24438485
TI  - Computed tomography of ball pythons (Python regius) in curled recumbency.
AB  - Anesthesia and tube restraint methods are often required for computed tomography
      (CT) of snakes due to their natural tendency to curl up. However, these restraint
      methods may cause animal stress. The aim of this study was to determine whether
      the CT appearance of the lungs differs for ball pythons in a curled position vs.
      tube restraint. Whole body CT was performed on ten clinically healthy ball
      pythons, first in curled and then in straight positions restrained in a tube.
      Curved multiplanar reformatted (MPR) lung images from curled position scans were
      compared with standard MPR lung images from straight position scans. Lung
      attenuation and thickness were measured at three locations for each scan. Time
      for positioning and scanning was 12 +/- 5 min shorter for curled snakes compared
      to tube restraint. Lung parenchyma thickness and attenuation declined from
      cranial to caudal on both straight and curled position images. Mean lung
      parenchyma thickness was greater in curled images at locations 1 (P = 0.048) and
      3 (P = 0.044). Mean lung parenchyma thickness decreased between location 1 and 2
      by 86-87% (straight: curled) and between location 1 and 3 by 51-50% (straight:
      curled). Mean lung attenuation at location 1 was significantly greater on curled
      position images than tube restraint images (P = 0.043). Findings indicated that
      CT evaluation of the lungs is feasible for ball pythons positioned in curled
      recumbency if curved MPR is available. However, lung parenchyma thickness and
      attenuation in some locations may vary from those acquired using tube restraint. 

PMID- 24438486
TI  - Respiratory-gated PET/CT versus delayed images for the quantitative evaluation of
      lower pulmonary and hepatic lesions.
AB  - PURPOSE: Respiratory motion degrades fluorodeoxyglucose positron emission
      tomography (FDG PET) images of the lower chest and upper abdomen, as the blur
      introduced by breathing motion increases the apparent size of the moving tumour
      lesions and decreases their apparent uptake, reducing the sensitivity of PET in
      detection of small lesions. We assessed the role of delayed and respiratory-gated
      PET acquisition in the quantitative evaluation of lung and liver lesions.
      METHODS: A retrospective analysis of 64 lesions was performed. After initial non
      gated whole-body PET/CT, respiratory gating was performed with 15 min in list
      mode. Non-gated delayed images were obtained by summing all list mode data.
      SUV(max) adjusted for lean body mass (SUL(max)) was measured in the initial whole
      body scan, the delayed non-gated scans and the individual gated bins for each
      lesion. The axial z-position of SUL(max) for each lesion in five respiratory
      gated bins was determined. The mean SUL of the non-pathological liver parenchyma
      was also recorded for each patient. RESULTS: Tumour lesion SUL(max) increased by
      an average of 34% in the delayed non-gated scan as compared with the whole-body
      initial scan and further by an additional 17.2% in respiratory-gated images. The
      maximum lesion displacement was 6.2 +/- 5.0 mm. CONCLUSION: Delayed imaging alone
      substantially increases the magnitude of the SUL of liver and lung lesions as
      compared with standard whole-body images and may allow for a more accurate
      definition of the lesion's volume and localisation and improve tracer
      quantitation in malignant lesions in the lungs or upper abdomen. While
      respiratory gating provides more optimal imaging with greatest increase in
      SUL(max), the benefit is small, and delayed imaging appears sufficient in most
      cases.

PMID- 24438488
TI  - The transcription factor CCAAT enhancer-binding protein beta protects rat
      cerebellar granule neurons from apoptosis through its transcription-activating
      isoforms.
AB  - CCAAT enhancer-binding protein beta is a transcription factor that is involved in
      many brain processes, although its role in neuronal survival/death remains
      unclear. By using primary cultures of rat cerebellar granule neurons, we have
      shown here that CCAAT enhancer-binding protein beta is present as all of its
      isoforms: the transcriptional activators liver activator proteins 1 and 2, and
      the transcriptional inhibitor liver inhibitory protein. We have also shown that
      liver activator protein 1 undergoes post-translational modifications, such as
      phosphorylation and sumoylation. These isoforms have different subcellular
      localizations, liver activator protein 2 being found in the cytosolic fraction
      only, liver inhibitory protein in the nucleus only, and liver activator protein 1
      in both fractions. Through neuronal apoptosis induction by shifting mature
      cerebellar granule neurons to low-potassium medium, we have demonstrated that
      nuclear liver activator protein 1 expression decreases and its phosphorylation
      disappears, whereas liver inhibitory protein levels increase in the nuclear
      fraction, suggesting a pro-survival role for liver activator protein
      transcriptional activation and a pro-apoptotic role for liver inhibitory protein
      transcriptional inhibition. To confirm this, we transfected cerebellar granule
      neurons with plasmids expressing liver activator protein 1, liver activator
      protein 2, or liver inhibitory protein respectively, and observed that both liver
      activator proteins, which increase CCAAT-dependent transcription, but not liver
      inhibitory protein, counteracted apoptosis, thus demonstrating the pro-survival
      role of liver activator proteins. These data significantly improve our current
      understanding of the role of CCAAT enhancer-binding protein beta in neuronal
      survival/apoptosis. 

PMID- 24438487
TI  - Neuronal and astrocytic interactions modulate brain endothelial properties during
      metabolic stresses of in vitro cerebral ischemia.
AB  - Neurovascular and gliovascular interactions significantly affect endothelial
      phenotype. Physiologically, brain endothelium attains several of its properties
      by its intimate association with neurons and astrocytes. However, during
      cerebrovascular pathologies such as cerebral ischemia, the uncoupling of
      neurovascular and gliovascular units can result in several phenotypical changes
      in brain endothelium. The role of neurovascular and gliovascular uncoupling in
      modulating brain endothelial properties during cerebral ischemia is not clear.
      Specifically, the roles of metabolic stresses involved in cerebral ischemia,
      including aglycemia, hypoxia and combined aglycemia and hypoxia (oxygen glucose
      deprivation and re-oxygenation, OGDR) in modulating neurovascular and
      gliovascular interactions are not known. The complex intimate interactions in
      neurovascular and gliovascular units are highly difficult to recapitulate in
      vitro. However, in the present study, we used a 3D co-culture model of brain
      endothelium with neurons and astrocytes in vitro reflecting an intimate
      neurovascular and gliovascular interactions in vivo. While the cellular signaling
      interactions in neurovascular and gliovascular units in vivo are much more
      complex than the 3D co-culture models in vitro, we were still able to observe
      several important phenotypical changes in brain endothelial properties by
      metabolically stressed neurons and astrocytes including changes in barrier,
      lymphocyte adhesive properties, endothelial cell adhesion molecule expression and
      in vitro angiogenic potential. 

PMID- 24438489
TI  - Periodic properties of the histaminergic system of the mouse brain.
AB  - Brain histamine is involved in the regulation of the sleep-wake cycle and
      alertness. Despite the widespread use of the mouse as an experimental model, the
      periodic properties of major markers of the mouse histaminergic system have not
      been comprehensively characterized. We analysed the daily levels of histamine and
      its first metabolite, 1-methylhistamine, in different brain structures of
      C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine
      decarboxylase and histamine-N-methyltransferase in C57BL/6J mice. In the C57BL/6J
      strain, histamine release, assessed by in vivo microdialysis, underwent prominent
      periodic changes. The main period was 24 h peaking during the activity period.
      Additional 8 h periods were also observed. The release was highly positively
      correlated with active wakefulness, as shown by electroencephalography. In both
      mouse strains, tissue histamine levels remained steady for 24 h in all structures
      except for the hypothalamus of CBA/J mice, where 24-h periodicity was observed.
      Brain tissue 1-methylhistamine levels in both strains reached their maxima in the
      periods of activity. The mRNA level of histidine decarboxylase in the
      tuberomamillary nucleus and the activities of histidine decarboxylase and
      histamine-N-methyltransferase in the striatum and cortex did not show a 24-h
      rhythm, whereas in the hypothalamus the activities of both enzymes had a 12-h
      periodicity. These results show that the activities of histamine-metabolizing
      enzymes are not under simple direct circadian regulation. The complex and non
      uniform temporal patterns of the histaminergic system of the mouse brain suggest
      that histamine is strongly involved in the maintenance of active wakefulness. 

PMID- 24438490
TI  - Dual regulation of clock gene Per2 expression in discrete brain areas by the
      circadian pacemaker and methamphetamine-induced oscillator in rats.
AB  - Behavioral rhythms induced by methamphetamine (MAP) treatment in rats are
      independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). To
      know the site and mechanism of an underlying oscillation (MAP-induced oscillator;
      MAO), extra-SCN circadian rhythms in the discrete brain areas were examined in
      rats with and without the SCN. To fix the phase of MAO, MAP was supplied in
      drinking water at a restricted time of day for 14 days (R-MAP) and subsequently
      given ad libitum (ad-MAP). Plain water was given to the controls at the same
      restricted time (R-Water). Clock gene Per2 expression was measured by a
      bioluminescence reporter in cultured brain tissues. In SCN-intact rats, MAO was
      induced by R-MAP and behavioral rhythms were phase-delayed from the restricted
      time under ad-MAP with relative coordination. Circadian Per2 rhythms in R-MAP
      rats were not affected in the SCN but were slightly phase-advanced in the
      olfactory bulb (OB), caudate-putamen (CPU) and substantia nigra (SN) as compared
      with R-Water rats. Following SCN lesion, R-MAP-induced MAO phase-shifted more
      slowly and did not show a sign of relative coordination. In these rats, circadian
      Per2 rhythms were significantly phase-shifted in the OB and SN as compared with
      SCN-intact rats. These findings indicate that MAO was induced by MAP given at a
      restricted time of day in association with phase-shifts of the extra-SCN
      circadian oscillators in the brain dopaminergic areas. The findings also suggest
      that these extra-SCN oscillators are the components of MAO and receive dual
      regulation by MAO and the SCN circadian pacemaker. 

PMID- 24438491
TI  - Task difficulty in mental arithmetic affects microsaccadic rates and magnitudes.
AB  - Microsaccades are involuntary, small-magnitude saccadic eye movements that occur
      during attempted visual fixation. Recent research has found that attention can
      modulate microsaccade dynamics, but few studies have addressed the effects of
      task difficulty on microsaccade parameters, and those have obtained contradictory
      results. Further, no study to date has investigated the influence of task
      difficulty on microsaccade production during the performance of non-visual tasks.
      Thus, the effects of task difficulty on microsaccades, isolated from sensory
      modality, remain unclear. Here we investigated the effects of task difficulty on
      microsaccades during the performance of a non-visual, mental arithmetic task with
      two levels of complexity. We found that microsaccade rates decreased and
      microsaccade magnitudes increased with increased task difficulty. We propose that
      changes in microsaccade rates and magnitudes with task difficulty are mediated by
      the effects of varying attentional inputs on the rostral superior colliculus
      activity map. 

PMID- 24438492
TI  - Online decoding of object-based attention using real-time fMRI.
AB  - Visual attention is used to selectively filter relevant information depending on
      current task demands and goals. Visual attention is called object-based attention
      when it is directed to coherent forms or objects in the visual field. This study
      used real-time functional magnetic resonance imaging for moment-to-moment
      decoding of attention to spatially overlapped objects belonging to two different
      object categories. First, a whole-brain classifier was trained on pictures of
      faces and places. Subjects then saw transparently overlapped pictures of a face
      and a place, and attended to only one of them while ignoring the other. The
      category of the attended object, face or place, was decoded on a scan-by-scan
      basis using the previously trained decoder. The decoder performed at 77.6%
      accuracy indicating that despite competing bottom-up sensory input, object-based
      visual attention biased neural patterns towards that of the attended object.
      Furthermore, a comparison between different classification approaches indicated
      that the representation of faces and places is distributed rather than focal.
      This implies that real-time decoding of object-based attention requires a
      multivariate decoding approach that can detect these distributed patterns of
      cortical activity. 

PMID- 24438493
TI  - Anti-diabetic drug utilization of pregnant diabetic women in us managed care.
AB  - BACKGROUND: With the increasing prevalence of type 2 diabetes in young adulthood,
      treatment of diabetes in pregnancy faces new challenges. Anti-diabetic drug
      utilization patterns of pregnant women with pre-existing diabetes are poorly
      described. We aim to describe anti-diabetic (AD) agent utilization among diabetic
      pregnant women. METHODS: We utilized IMS LifeLink, including administrative
      claims data of patients in US managed care plans, to establish a retrospective
      cohort of women, age 18-46 years (N = 96,740) with billed procedures for a live
      birth, and a 12 month eligibility period before and 3 month after delivery.
      Diabetes mellitus was identified from >=2 in- or outpatient claims with diagnoses
      (ICD-9-CM 250.XX) before pregnancy. We estimated the prevalence of AD drugs
      before, during and after pregnancy, and secular trends across the study period
      (1999-2009), using linear regression. A sensitivity analysis was conducted to
      identify the extent of misclassification of trimesters. RESULTS: Almost six
      percent (n = 5,581) of the live birth cohort had diabetes mellitus. Throughout
      the study, 48% (1999) and 78% (2009) (p < 0.0001) of diabetic women received AD
      drugs during pregnancy. The most common AD drugs during pregnancy were insulin,
      metformin, sulfonylureas, thiazolidinediones (TZD), and combination AD. The
      annual prevalence of insulin use increased by only 1% from 39% (1999) to 40%
      (2009) (p = 0.589) during pregnancy, while use of sulfonylureas and metformin
      increased from 2.5% and 4.2% (1999) to 17.3% and 15.3% (2009) (p < 0.0001),
      respectively. Insulin and sulfonylurea use steadily increased in prevalence from
      the 1st to 3rd trimester (16.5% and 3.3% to 33.0% and 7.5%), while metformin and
      TZD use decreased (11.4% and 1.6% to 3.8% and 0.2%). CONCLUSIONS: AD use during
      pregnancy demonstrates the need for additional investigation regarding safety and
      efficacy of AD drugs on maternal outcomes.

PMID- 24438494
TI  - Effects of slaughtering operations on carcass contamination in an Irish pork
      production plant.
AB  - BACKGROUND: Microbiological standards within pork slaughter processing plants in
      the European Union are currently governed by Commission Regulation (EC)
      2073/2005, which describes detailed performance criteria at specific stages of
      the procedure (following carcass dressing and before chilling) for total viable
      counts (TVC), Enterobacteriaceae (EB) and Salmonella spp. In this study, 95
      carcasses from an Irish pork slaughter plant were sampled by swabbing 100 cm2 of
      surface at three sites (belly, ham, jowl) to examine the effects of eight
      processing stages (stunning, bleeding, scalding, singeing, polishing,
      evisceration, final inspection and chilling) on contamination levels. RESULTS:
      TVC ranged from approximately 1.7-6.3 log cfu cm2 during sampling. There were
      significant reductions in TVC for all sites after scalding and singeing (p <
      0.05), whilst there was a significant increase in counts after polishing and
      evisceration (p < 0.05) compared with preceding stages. EB counts indicated
      hygienic weak points in the examined slaughter plant leading to faecal (cross)
      contamination, with elevated counts after stunning, bleeding and evisceration (p
      < 0.05), compared with final counts after chilling. CONCLUSIONS: Although the
      bacterial numbers reported in this study may reflect specific plant practices and
      temporal influences, results show that contamination can be introduced at various
      steps in the process and highlight the importance of monitoring locations other
      than those required by legislation within the process. Monitoring can be used to
      establish baseline levels for high-risk stages specific to each plant and to
      assess the effectiveness of additional interventions.

PMID- 24438495
TI  - Decision-making factors affecting different family members regarding the
      placement of relatives in long-term care facilities.
AB  - BACKGROUND: The aim of this research was to investigate factors affecting
      different family members' decisions regarding the placement of relatives in long
      term car (LTC) facilities in Taiwan. The objective was to investigate the
      correlations between family members' personal traits, the living conditions of
      residents in the LTC facilities, and family members' experiences with LTC
      facilities. METHODS: This study selected family members visiting residents in LTC
      facilities as research subjects and used a structured questionnaire to perform
      face-to-face interviews. This study used nonlinear canonical correlation analysis
      (OVERALS) to categorize the decision-making factors affecting family members'
      choices of LTC facilities. RESULTS: The results showed that when making decisions
      about the placement of family members, spouses chose facilities according to
      their own life experiences, children considered medical treatment convenience,
      grandchildren preferred to collect relevant information on facilities, and other
      relatives preferred to decide based on introductions from government departments.
      CONCLUSIONS: These results help clarify how different family roles affect
      decision-making processes regarding the choice of LTC facilities. In particular,
      spouses and female relatives require an interventional service mechanism that
      provides consultation or referral information.

PMID- 24438496
TI  - Mobile biofeedback of heart rate variability in patients with diabetic
      polyneuropathy: a preliminary study.
AB  - Biofeedback of heart rate variability (HRV) was applied to patients with diabetic
      polyneuropathy using a new mobile device allowing regularly scheduled self
      measurements without the need of visits to a special autonomic laboratory.
      Prolonged generation of data over an eight-week period facilitated more precise
      investigation of cardiac autonomic function and assessment of positive and
      negative trends of HRV parameters over time. Statistical regression analyses
      revealed significant trends in 11 of 17 patients, while no significant
      differences were observed when comparing autonomic screening by short-term HRV
      and respiratory sinus arrhythmia at baseline and after the 8 weeks training
      period. Four patients showed positive trends of HRV parameters despite the
      expected progression of cardiac autonomic dysfunction over time. Patient
      compliance was above 50% in all but two patients. The results of this preliminary
      study indicate a good practicality of the handheld device and suggest a potential
      positive effect on cardiac autonomic neuropathy in patients with type 2 diabetes.

PMID- 24438497
TI  - Using CRP in neonatal practice.
AB  - OBJECTIVE: C-reactive protein (CRP) is the most widely used infection marker in
      neonatal practice. Combined with difficulty in early recognition of neonatal
      sepsis, the number of infants with risk factors for infection, and postnatal
      maladaptation of non-infectious origin; CRP is often used as a decision making
      tool for antibiotic therapy. We wished to examine practice regarding neonatal
      infection and use of CRP. METHODS: We designed an online multiple choice
      questionnaire, asking senior clinicians for their response to realistic postnatal
      ward scenarios. RESULTS: We had 91 replies, showing a great degree of variation,
      with no pattern emerging for experience, region, or even individual neonatal
      units. This was true even for situations covered by the guidelines that have an
      evidence basis. CONCLUSIONS: A recurring theme was duration of antibiotic therapy
      for an elevated CRP, and once levels are falling, when it is safe to stop
      treatment. Given a lack of good quality evidence, the National Institute of
      Clinical Excellence (NICE) guidelines are purposefully non-specific. Further
      research is required, and if incorporated in future national guidelines, should
      help promote more widespread use and so reduce potential over- and under
      treatment of this patient subset. However, this also requires a greater
      willingness on the part of pediatricians to ensure practice is evidence based.

PMID- 24438498
TI  - A prostaglandin D-synthase-positive mast cell gradient characterizes scalp
      patterning.
AB  - BACKGROUND: Pattern (androgenetic) alopecia is commonly encountered in scalp
      biopsies obtained for non-scarring hair loss. Prostaglandin D-synthase is known
      to be elevated in bald vs. non-alopetic scalp of patients with androgenetic
      alopecia. We hypothesized that this difference in pattern of prostaglandin D
      synthase expression may constitute a developmental pattern inherent to normal as
      well as alopecic scalp skin, thus defining a 'field' vulnerable to acquired hair
      loss. METHODS: We immunohistochemically mapped prostaglandin D-synthase
      expression from supra-auricular to vertex scalp skin of 11 cadavers. RESULTS: We
      found significantly more dermal mast cells immunoreactive for prostaglandin D
      synthase in the vertex compared to the lateral aspects of the scalp, with a
      decrement that spatially approximated the pattern of androgenetic alopecia. This
      difference was present in both balding and non-balding scalps and was independent
      of gender. Dual labeling established dermal cells expressing prostaglandin D
      synthase as mast cells. CONCLUSIONS: These data indicate that scalp is spatially
      programmed via mast cell prostaglandin D-synthase distribution in a manner
      reminiscent of the pattern seen in androgenetic alopecia.

PMID- 24438499
TI  - Evaluating the composition and processing potential of novel sources of Brazilian
      biomass for sustainable biorenewables production.
AB  - BACKGROUND: The search for promising and renewable sources of carbohydrates for
      the production of biofuels and other biorenewables has been stimulated by an
      increase in global energy demand in the face of growing concern over greenhouse
      gas emissions and fuel security. In particular, interest has focused on non-food
      lignocellulosic biomass as a potential source of abundant and sustainable
      feedstock for biorefineries. Here we investigate the potential of three Brazilian
      grasses (Panicum maximum, Pennisetum purpureum and Brachiaria brizantha), as well
      as bark residues from the harvesting of two commercial Eucalyptus clones (E.
      grandis and E. grandis x urophylla) for biofuel production, and compare these to
      sugarcane bagasse. The effects of hot water, acid, alkaline and sulfite
      pretreatments (at increasing temperatures) on the chemical composition,
      morphology and saccharification yields of these different biomass types were
      evaluated. RESULTS: The average yield (per hectare), availability and general
      composition of all five biomasses were compared. Compositional analyses indicate
      a high level of hemicellulose and lignin removal in all grass varieties
      (including sugarcane bagasse) after acid and alkaline pretreatment with
      increasing temperatures, whilst the biomasses pretreated with hot water or
      sulfite showed little variation from the control. For all biomasses, higher
      cellulose enrichment resulted from treatment with sodium hydroxide at 130 degrees
      C. At 180 degrees C, a decrease in cellulose content was observed, which is
      associated with high amorphous cellulose removal and 5-hydroxymethyl-furaldehyde
      production. Morphological analysis showed the effects of different pretreatments
      on the biomass surface, revealing a high production of microfibrillated cellulose
      on grass surfaces, after treatment with 1% sodium hydroxide at 130 degrees C for
      30 minutes. This may explain the higher hydrolysis yields resulting from these
      pretreatments, since these cellulosic nanoparticles can be easily accessed and
      cleaved by cellulases. CONCLUSION: Our results show the potential of three
      Brazilian grasses with high productivity yields as valuable sources of
      carbohydrates for ethanol production and other biomaterials. Sodium hydroxide at
      130 degrees C was found to be the most effective pretreatment for enhanced
      saccharification yields. It was also efficient in the production of
      microfibrillated cellulose on grass surfaces, thereby revealing their potential
      as a source of natural fillers used for bionanocomposites production.

PMID- 24438501
TI  - Application of a vacuum pressure impregnation technique for rehydrating
      decellularized tissues.
AB  - Most of the clinically available decellularized tissues are preserved in a freeze
      dried state. Freeze-dried (FD) tissues can be preserved for long term, although a
      rehydration process is necessary before use. Currently, an immersion method is
      most commonly used in clinical procedures, but it is difficult for complicated
      and thick structure tissue rehydration. In this study, we tried to apply a vacuum
      pressure impregnation (VPI) technique for FD tissue rehydration. The water
      content of decellularized tissues can reach the water content of native tissues
      within 30 min using VPI, whereas it took 6 h to reach the same water content
      using the immersion method. Furthermore, heparin rehydrated aortas by VPI had
      more heparin release at each time point and therefore appeared more anticoagulant
      activity. We found that the VPI treatment promotes solution infiltration into
      materials, achieves complete rehydration of the decellularized tissues, and deep
      infiltration of heparin into the decellularized tissues, suggesting that VPI
      treatment could be applied as a rehydration method for biological materials.

PMID- 24438500
TI  - LOCAT (low-dose computed tomography for appendicitis trial) comparing clinical
      outcomes following low- vs standard-dose computed tomography as the first-line
      imaging test in adolescents and young adults with suspected acute appendicitis:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Computed tomography is widely used to diagnose acute appendicitis.
      Many adolescents and young adults are exposed to the associated radiation. A
      recent single-institution trial has reported promising results for low-dose
      computed tomography; however, this technique has not yet been widely adopted.
      LOCAT (low-dose computed tomography for appendicitis trial), a multi-institution
      randomized controlled non-inferiority trial, aims to compare low-dose computed
      tomography and standard-dose computed tomography as the first-line imaging tests
      for adolescents and young adults, and therefore to test the generalizability of
      the previous single-institution trial results. METHODS/DESIGN: Participants with
      suspected appendicitis are randomly assigned to either the low-dose group (with a
      typical effective dose of 2 mSv) or the standard-dose group (as used in normal
      practice at each participating site, typically 8 mSv). The primary end point is
      the negative appendectomy rate (the percentage of the number of uninflamed
      appendices that were removed among all non-incidental appendectomies), which is a
      consequence of false-positive diagnoses, with a non-inferiority margin of 4.5
      percentage points. The key secondary end point is the appendiceal perforation
      rate, which is a consequence of delayed (or false-negative) diagnoses.
      Participant recruitment will be continued until the number of non-incidental
      appendectomies for each group exceeds 444. The total number of expected
      participants approximates 3,000, including those not undergoing appendectomy.
      DISCUSSION: In addition to the study protocol, we elaborate on several
      challenging or potentially debatable components of the study design, including
      the broad eligibility criteria, choice of the primary end point, potential effect
      of using advanced imaging techniques on study results, determining and adjusting
      the radiation doses, ambiguities in reference standards, rationale for the non
      inferiority margin, use of the intention-to-treat approach and difficulties in
      defining adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT01925014.

PMID- 24438503
TI  - A new type of dual atrioventricular nodal nonreentrant tachycardia.
AB  - Dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) is very rarely
      observed clinically. The first review of this arrhythmia was published in 2011 by
      Wang, where four types of DAVNNT were described. Our case report presents a
      phenomenon that has never been published before. We revealed a very specific
      sequence of double fire phenomenon, 1:1 atrioventricular (AV) conduction and AV
      block. 

PMID- 24438502
TI  - Integrated transcriptome analysis of mouse spermatogenesis.
AB  - BACKGROUND: Differentiation of primordial germ cells into mature spermatozoa
      proceeds through multiple stages, one of the most important of which is meiosis.
      Meiotic recombination is in turn a key part of meiosis. To achieve the highly
      specialized and diverse functions necessary for the successful completion of
      meiosis and the generation of spermatozoa thousands of genes are coordinately
      regulated through spermatogenesis. A complete and unbiased characterization of
      the transcriptome dynamics of spermatogenesis is, however, still lacking.
      RESULTS: In order to characterize gene expression during spermatogenesis we
      sequenced eight mRNA samples from testes of juvenile mice from 6 to 38 days post
      partum. Using gene expression clustering we defined over 1,000 novel meiotically
      expressed genes. We also developed a computational de-convolution approach and
      used it to estimate cell type-specific gene expression in pre-meiotic, meiotic
      and post-meiotic cells. In addition, we detected 13,000 novel alternative
      splicing events around 40% of which preserve an open reading frame, and found
      experimental support for 159 computational gene predictions. A comparison of RNA
      polymerase II (Pol II) ChIP-Seq signals with RNA-Seq coverage shows that gene
      expression correlates well with Pol II signals, both at promoters and along the
      gene body. However, we observe numerous instances of non-canonical promoter
      usage, as well as intergenic Pol II peaks that potentially delineate unannotated
      promoters, enhancers or small RNA clusters. CONCLUSIONS: Here we provide a
      comprehensive analysis of gene expression throughout mouse meiosis and
      spermatogenesis. Importantly, we find over a thousand of novel meiotic genes and
      over 5,000 novel potentially coding isoforms. These data should be a valuable
      resource for future studies of meiosis and spermatogenesis in mammals.

PMID- 24438504
TI  - Phase I study of combination chemotherapy using sorafenib and transcatheter
      arterial infusion with cisplatin for advanced hepatocellular carcinoma.
AB  - The aims of this study were to evaluate the frequency of dose-limiting toxicities
      and to find the recommended dose of combination chemotherapy with sorafenib and
      transcatheter arterial infusion (TAI) using cisplatin for patients with advanced
      hepatocellular carcinoma (HCC), for whom surgical resection, local ablation
      therapy, or transcatheter arterial chemoembolization were not indicated. Patients
      received 800 mg sorafenib daily. Cisplatin was given at one of three dosages
      (level 1, 35 mg/m(2) /cycle; level 2, 50 mg/m(2) /cycle; and level 3, 65 mg/m(2)
      /cycle) from feeding arteries to the HCC. The treatment was repeated every 4-6
      weeks up to a maximum of six cycles, until there were signs of tumor progression
      or unacceptable toxicity. The dose-limiting toxicities experienced by the 20
      enrolled patients were grade 4 increased aspartate aminotransferase at level 1,
      grade 3 gastrointestinal hemorrhaging at level 1, and grade 3 hypertension at
      level 3. The common drug-related adverse events that were of severity grade 3 or
      4 included the elevation of aspartate aminotransferase (30%), alanine
      aminotransferase (20%), amylase (30%), and lipase (30%). Partial response was
      seen in four patients (20%), and 13 patients (65%) had stable disease. The median
      overall survival and progression-free survival were 9.1 and 3.3 months,
      respectively. The combination of sorafenib at 800 mg/day with TAI of cisplatin at
      65 mg/m(2) /cycle was determined to be the recommended regimen. A randomized
      phase II trial of sorafenib alone versus sorafenib plus TAI of cisplatin is
      currently underway. This study was registered at UMIN as trial number
      UMIN000001496.

PMID- 24438505
TI  - A case of clozapine intoxication presenting with atypical NMS symptoms.

PMID- 24438506
TI  - Impact of platform switching on marginal peri-implant bone-level changes. A
      systematic review and meta-analysis.
AB  - OBJECTIVE: To address the focused question, is there an impact of platform
      switching (PS) on marginal bone level (MBL) changes around endosseous implants
      compared to implants with platform matching (PM) implant-abutment configurations?
      MATERIAL AND METHODS: A systematic literature search was conducted using
      electronic databases PubMed, Web of Science, Journals@Ovid Full Text and Embase,
      manual search for human randomized clinical trials (RCTs) and prospective
      clinical controlled cohort studies (PCCS) reporting on MBL changes at implants
      with PS-, compared with PM-implant-abutment connections, published between 2005
      and June 2013. RESULTS: Twenty-two publications were eligible for the systematic
      review. The qualitative analysis of 15 RCTs and seven PCCS revealed more studies
      (13 RCTs and three PCCS) showing a significantly less mean marginal bone loss
      around implants with PS- compared to PM-implant-abutment connections, indicating
      a clear tendency favoring the PS technique. A meta-analysis including 13 RCTs
      revealed a significantly less mean MBL change (0.49 mm [CI95% 0.38; 0.60]) at PS
      implants, compared with PM implants (1.01 mm [CI95% 0.62; 1.40] (P < 0.0001).
      CONCLUSIONS: The meta-analysis revealed a significantly less mean MBL change at
      implants with a PS compared to PM-implant-abutment configuration. Studies
      included herein showed an unclear as well as high risk of bias mostly, and
      relatively short follow-up periods. The qualitative analysis revealed a tendency
      favoring the PS technique to prevent or minimize peri-implant marginal bone loss
      compared with PM technique. Due to heterogeneity of the included studies, their
      results require cautious interpretation.

PMID- 24438508
TI  - Tuberculosis case finding and isoniazid preventive therapy among people living
      with HIV at public health facilities of Addis Ababa, Ethiopia: a cross-sectional
      facility based study.
AB  - BACKGROUND: Activities to decrease the burden of tuberculosis (TB) among people
      living with HIV (PLHIV) include intensified TB case-finding (ICF), Isoniaizid
      (INH) preventive therapy (IPT) and infection control in health-care and
      congregate settings (IC). Information about the status of collaborative TB/HIV
      care services which decreases the burden of TB among PLHIV in Ethiopia is
      limited. The purpose of the study was to assess TB case finding and provision of
      IPT among PLHIV in Addis Ababa. METHODS: A cross sectional, facility-based survey
      was conducted between June 2011 and August 2011. Data was collected by
      interviewing 849 PLHIV from ten health facilities in Addis Ababa. Both
      descriptive and inferential statistics were used to analyze findings and the
      results are described in this report. RESULTS: The proportion of PLHIV who have
      been screened for TB during any one of their follow-up cares was 92.8%. Eighty
      eight (10.4%) of the study participants have been diagnosed for TB during their
      HIV follow-up cares. PLHIV who had never been diagnosed for TB before they knew
      their positive HIV status were nearly four times more likely to be diagnosed for
      TB during follow-up cares than those diagnosed before (AOR [95% CI]: 3.78 [1.69
      8.43]). Nearly a third (28.7%) of all interviewed PLHIV self reported that they
      had been treated with IPT. CONCLUSIONS: It can be concluded that ICF for TB and
      IPT among PLHIV in Addis Ababa need boosting. Hence, it is recommended to put
      into practice the national and global guidelines to improve ICF and IPT among
      PLHIV in the city.

PMID- 24438509
TI  - Transcriptome resources for the perennial sunflower Helianthus maximiliani
      obtained from ecologically divergent populations.
AB  - Next-generation sequencing (NGS) technologies provide a rapid means to generate
      genomic resources for species exhibiting interesting ecological and evolutionary
      variation but for which such resources are scant or nonexistent. In the current
      report, we utilize 454 pyrosequencing to obtain transcriptome information for
      multiple individuals and tissue types from geographically disparate and
      ecologically differentiated populations of the perennial sunflower species
      Helianthus maximiliani. A total of 850 275 raw reads were obtained averaging 355
      bp in length. Reads were assembled, postprocessing, into 16 681 unique contigs
      with an N50 of 898 bp and a total length of 13.6 Mb. A majority (67%) of these
      contigs were annotated based on comparison with the Arabidopsis thaliana genome
      (TAIR10). Contigs were identified that exhibit high similarity to genes
      associated with natural variation in flowering time and freezing tolerance in
      other plant species and will facilitate future studies aimed at elucidating the
      molecular basis of clinal life history variation and adaptive differentiation in
      H. maximiliani. Large numbers of gene-associated simple sequence repeats (SSRs)
      and single-nucleotide polymorphisms (SNPs) also were identified that can be
      deployed in mapping and population genomic analyses.

PMID- 24438507
TI  - Annual research review: Current limitations and future directions in MRI studies
      of child- and adult-onset developmental psychopathologies.
AB  - BACKGROUND: The widespread use of Magnetic Resonance Imaging (MRI) in the study
      of child- and adult-onset developmental psychopathologies has generated many
      investigations that have measured brain structure and function in vivo throughout
      development, often generating great excitement over our ability to visualize the
      living, developing brain using the attractive, even seductive images that these
      studies produce. Often lost in this excitement is the recognition that brain
      imaging generally, and MRI in particular, is simply a technology, one that does
      not fundamentally differ from any other technology, be it a blood test, a
      genotyping assay, a biochemical assay, or behavioral test. No technology alone
      can generate valid scientific findings. Rather, it is only technology coupled
      with a strong experimental design that can generate valid and reproducible
      findings that lead to new insights into the mechanisms of disease and therapeutic
      response. METHODS: In this review we discuss selected studies to illustrate the
      most common and important limitations of MRI study designs as most commonly
      implemented thus far, as well as the misunderstanding that the interpretations of
      findings from those studies can create for our theories of developmental
      psychopathologies. RESULTS: Common limitations of MRI study designs are in large
      part responsible thus far for the generally poor reproducibility of findings
      across studies, poor generalizability to the larger population, failure to
      identify developmental trajectories, inability to distinguish causes from effects
      of illness, and poor ability to infer causal mechanisms in most MRI studies of
      developmental psychopathologies. For each of these limitations in study design
      and the difficulties they entail for the interpretation of findings, we discuss
      various approaches that numerous laboratories are now taking to address those
      difficulties, which have in common the yoking of brain imaging technologies to
      studies with inherently stronger designs that permit more valid and more powerful
      causal inferences. Those study designs include epidemiological, longitudinal,
      high-risk, clinical trials, and multimodal imaging studies. CONCLUSIONS: We
      highlight several studies that have yoked brain imaging technologies to these
      stronger designs to illustrate how doing so can aid our understanding of disease
      mechanisms and in the foreseeable future can improve clinical diagnosis,
      prevention, and treatment planning for developmental psychopathologies.

PMID- 24438510
TI  - Clinical features and risk factors for developing varicella zoster virus
      dissemination following hematopoietic stem cell transplantation.
AB  - BACKGROUND: We retrospectively analyzed 80 instances of varicella zoster virus
      (VZV) disease in 72 patients who underwent allogeneic hematopoietic stem cell
      transplantation (HSCT) and examined the clinical differences between localized
      and disseminated disease. Risk factors for developing VZV dissemination were also
      evaluated. RESULTS: Of the 80 instances, 54 instances were localized diseases and
      26 were disseminated diseases. Patient characteristics did not differ
      significantly between the 2 groups, except for the first-line therapy and the
      duration from symptom onset to treatment. In the disseminated group, intravenous
      acyclovir was used as the first-line therapy more frequently, and more time
      elapsed before beginning antiviral therapy compared with the localized group. In
      multivariate analyses, the duration from symptom onset to treatment was
      identified as an independent risk factor that significantly affected the
      development of VZV dissemination. Gender, total body irradiation, and chronic
      graft-versus-host disease, of which the latter 2 factors were reported as risk
      factors for the development of VZV disease after HSCT, did not affect the
      development of VZV dissemination. CONCLUSION: Our results suggest that VZV
      infection or reactivation may easily progress to viremia with delayed use of
      antiviral agents and may result in VZV dissemination in immunocompromised
      patients.

PMID- 24438511
TI  - Progressive adult antimetropia.
AB  - Antimetropia, a sub-classification of anisometropia, is a rare refractive
      condition in which one eye is myopic and the fellow eye is hyperopic. This case
      report describes the ocular characteristics and atypical refractive progression
      in an adult male with a moderate degree of non-amblyopic antimetropia over a 20
      year period. The potential mechanisms underlying unilateral axial elongation,
      anisometropia and myopia progression in adulthood are discussed. 

PMID- 24438513
TI  - Evaluation of the WARP-turbo spin echo sequence for 3 Tesla magnetic resonance
      imaging of stifle joints in dogs with stainless steel tibial plateau leveling
      osteotomy implants.
AB  - Susceptibility artifacts caused by ferromagnetic implants compromise magnetic
      resonance imaging (MRI) of the canine stifle after tibial plateau leveling
      osteotomy (TPLO) procedures. The WARP-turbo spin echo sequence is being developed
      to mitigate artifacts and utilizes slice encoding for metal artifact reduction.
      The aim of the current study was to evaluate the WARP-turbo spin echo sequence
      for imaging post TPLO canine stifle joints. Proton density weighted images of 19
      canine cadaver limbs were made post TPLO using a 3 Tesla MRI scanner.
      Susceptibility artifact sizes were recorded and compared for WARP vs.
      conventional turbo spin echo sequences. Three evaluators graded depiction quality
      for the tibial tuberosity, medial and lateral menisci, tibial osteotomy, and
      caudal cruciate ligament as sufficient or insufficient to make a diagnosis.
      Artifacts were subjectively smaller and local structures were better depicted in
      WARP-turbo spin echo images. Signal void area was also reduced by 75% (sagittal)
      and 49% (dorsal) in WARP vs. conventional turbo spin echo images. Evaluators were
      significantly more likely to grade local anatomy depiction as adequate for making
      a diagnosis in WARP-turbo spin echo images in the sagittal but not dorsal plane.
      The proportion of image sets with anatomic structure depiction graded adequate to
      make a diagnosis ranged from 28 to 68% in sagittal WARP-turbo spin echo images
      compared to 0-19% in turbo spin echo images. Findings indicated that the WARP
      turbo spin echo sequence reduces the severity of susceptibility artifacts in
      canine stifle joints post TPLO. However, variable depiction of local anatomy
      warrants further refinement of the technique. 

PMID- 24438512
TI  - Autologous mesenchymal stem cell therapy for progressive supranuclear palsy:
      translation into a phase I controlled, randomized clinical study.
AB  - BACKGROUND: Progressive Supranuclear Palsy (PSP) is a sporadic and progressive
      neurodegenerative disease which belongs to the family of tauopathies and involves
      both cortical and subcortical structures. No effective therapy is to date
      available. METHODS/DESIGN: Autologous bone marrow (BM) mesenchymal stem cells
      (MSC) from patients affected by different type of parkinsonisms have shown their
      ability to improve the dopaminergic function in preclinical and clinical models.
      It is also possible to isolate and expand MSC from the BM of PSP patients with
      the same proliferation rate and immuphenotypic profile as MSC from healthy
      donors. BM MSC can be efficiently delivered to the affected brain regions of PSP
      patients where they can exert their beneficial effects through different
      mechanisms including the secretion of neurotrophic factors.Here we propose a
      randomized, placebo-controlled, double-blind phase I clinical trial in patients
      affected by PSP with MSC delivered via intra-arterial injection. DISCUSSION: To
      our knowledge, this is the first clinical trial to be applied in a no-option
      parkinsonism that aims to test the safety and to exploit the properties of
      autologous mesenchymal stem cells in reducing disease progression. The study has
      been designed to test the safety of this "first-in-man" approach and to
      preliminarily explore its efficacy by excluding the placebo effect. TRIAL
      REGISTRATION: NCT01824121.

PMID- 24438514
TI  - A selection strategy in plant transformation based on antisense
      oligodeoxynucleotide inhibition.
AB  - Antisense oligodeoxynucleotide (asODN) inhibition was developed in the 1970s, and
      since then has been widely used in animal research. However, in plant biology,
      the method has had limited application because plant cell walls significantly
      block efficient uptake of asODN to plant cells. Recently, we have found that
      asODN uptake is enhanced in a sugar solution. The method has promise for many
      applications, such as a rapid alternative to time-consuming transgenic studies,
      and high potential for studying gene functionality in intact plants and multiple
      plant species, with particular advantages in evaluating the roles of multiple
      gene family members. Generation of transgenic plants relies on the ability to
      select transformed cells. This screening process is based on co-introduction of
      marker genes into the plant cell together with a gene of interest. Currently, the
      most common marker genes are those that confer antibiotic or herbicide
      resistance. The possibility that traits introduced by selectable marker genes in
      transgenic field crops may be transferred horizontally is of major public
      concern. Marker genes that increase use of antibiotics and herbicides may
      increase development of antibiotic-resistant bacterial strains or contribute to
      weed resistance. Here, we describe a method for selection of transformed plant
      cells based on asODN inhibition. The method enables selective and high-throughput
      screening for transformed cells without conferring new traits or functions to the
      transgenic plants. Due to their high binding specificity, asODNs may also find
      applications as plant-specific DNA herbicides. 

PMID- 24438515
TI  - Assessing mobility difficulties for cross-national comparisons: results from the
      World Health Organization Study on Global AGEing and Adult Health.
AB  - OBJECTIVES: To assess the correspondence between self-reported and measured
      indicators of mobility disability in older adults in six low- and middle-income
      countries (LMICs). DESIGN: Cross-sectional analysis of Study on Global AGEing and
      Adult Health (SAGE). SETTING: Household surveys in China, India, Russia, South
      Africa, Ghana, and Mexico. PARTICIPANTS: Community-dwelling SAGE respondents aged
      65 and older (N = 12,215). MEASUREMENTS: Objective mobility was assessed
      according to a 4-m timed walk at normal pace conducted in the respondent's home;
      slow walking speed was defined according to the Fried frailty criteria (lowest
      quintile of walking speed, adjusted for age and height). Self-reported mobility
      difficulty was assessed according to a question about ability to walk 1 km; this
      response was dichotomized into any versus no self-reported difficulty walking 1
      km (reference no difficulty). The age- (5-year groups) and sex-specific
      probability of self-reporting difficulty walking 1 km was estimated in those with
      a measured slow walk using logistic regression. RESULTS: Between 42% and 76% of
      people aged 65 and older reported any difficulty walking 1 km. Average walking
      speed was slowest in Russia (0.61 m/s) and fastest in China (0.88 m/s). The
      probabilities of reporting any difficulty walking 1 km in women aged 65 to 69,
      for example, with a slow walk varied (China = 0.35, India = 0.90, Russia = 0.68,
      South Africa = 0.81, Ghana = 0.91, Mexico = 0.73; test of country differences P <
      .001). There was significant variation at older ages, albeit smaller in
      magnitude. Patterns were similar for men. CONCLUSION: Although correspondence
      between an objective and self-reported measure of mobility was generally high,
      correspondence differed significantly between LMICs. International comparisons of
      self-reported disability measures for clinical, prevention, and policy guidelines
      in LMICs should consider that self-reported data may not correspond to objective
      measures uniformly between countries.

PMID- 24438516
TI  - Aerobic exercise increases phosphate removal during hemodialysis: a controlled
      trial.
AB  - Previous studies have suggested that exercise during hemodialysis (HD) could
      increase the efficacy of solute removal, although this hypothesis has not been
      conclusively evaluated. The goal of this study was to compare the removal of low
      molecular weight solutes between HD sessions, with and without aerobic exercise.
      It was a controlled clinical trial, including HD patients in a randomly cross
      over design, such that each patient received a HD session with exercise
      (intervention) and the next one without exercise (control), three times each. In
      the exercise sessions, patients pedaled on a cycle ergometer for 60 minutes. The
      total mass of removed urea, potassium, creatinine, and phosphate were calculated
      from the solutes concentration in dialysate (continuous spent sampling of
      dialysate). This was evaluated in a total of 132 HD sessions of patients with a
      mean age of 54 +/- 15 years, 75% male and HD vintage of 3 (2-13) years. Phosphate
      removal in dialysate during intervention sessions was significantly higher (5.6
      [2.5-18.9] vs. 5.1 [1.5-11.2] mg/min) than during control sessions, P = 0.04. The
      median mass of phosphate removed during control HD session was 1226 (367.8
      2697.2) vs. 1348.6 (613.0-4536.2) mg/session during intervention sessions. The
      exercise did not modify the removal of urea (control 122.6 [61.3-286.0] vs.
      exercise 112.4 [51.1-250.3] mg/min, P = 0.44), creatinine (control 5.6 [2.5-13.8]
      vs. exercise 5.6 [2.5-12.8] mg/min, P = 0.49), or potassium (control 13.3 [11.2
      15.8] vs. exercise 13.8 [6.6-15.8] mEq/min, P = 0.49). Aerobic exercise during HD
      increases the efficacy of phosphate removal, without changing urea, creatinine
      and potassium removal. The implications of this finding in mineral and bone
      disease and cardiovascular disease need to be evaluated on future clinical
      trials.

PMID- 24438517
TI  - Mobile phones improve antenatal care attendance in Zanzibar: a cluster randomized
      controlled trial.
AB  - BACKGROUND: Applying mobile phones in healthcare is increasingly prioritized to
      strengthen healthcare systems. Antenatal care has the potential to reduce
      maternal morbidity and improve newborns' survival but this benefit may not be
      realized in sub-Saharan Africa where the attendance and quality of care is
      declining. We evaluated the association between a mobile phone intervention and
      antenatal care in a resource-limited setting. We aimed to assess antenatal care
      in a comprehensive way taking into consideration utilisation of antenatal care as
      well as content and timing of interventions during pregnancy. METHODS: This study
      was an open label pragmatic cluster-randomised controlled trial with primary
      healthcare facilities in Zanzibar as the unit of randomisation. 2550 pregnant
      women (1311 interventions and 1239 controls) who attended antenatal care at
      selected primary healthcare facilities were included at their first antenatal
      care visit and followed until 42 days after delivery. 24 primary health care
      facilities in six districts were randomized to either mobile phone intervention
      or standard care. The intervention consisted of a mobile phone text-message and
      voucher component. Primary outcome measure was four or more antenatal care visits
      during pregnancy. Secondary outcome measures were tetanus vaccination, preventive
      treatment for malaria, gestational age at last antenatal care visit, and
      antepartum referral. RESULTS: The mobile phone intervention was associated with
      an increase in antenatal care attendance. In the intervention group 44% of the
      women received four or more antenatal care visits versus 31% in the control group
      (OR, 2.39; 95% CI, 1.03-5.55). There was a trend towards improved timing and
      quality of antenatal care services across all secondary outcome measures although
      not statistically significant. CONCLUSIONS: The wired mothers' mobile phone
      intervention significantly increased the proportion of women receiving the
      recommended four antenatal care visits during pregnancy and there was a trend
      towards improved quality of care with more women receiving preventive health
      services, more women attending antenatal care late in pregnancy and more women
      with antepartum complications identified and referred. Mobile phone applications
      may contribute towards improved maternal and newborn health and should be
      considered by policy makers in resource-limited settings.

PMID- 24438519
TI  - Manipulating the extracellular matrix and its role in brain and spinal cord
      plasticity and repair.
AB  - Brain and spinal cord injury can result in permanent cognitive, motor, sensory
      and autonomic deficits. The central nervous system (CNS) has a poor intrinsic
      capacity for regeneration, although some functional recovery does occur. This is
      mainly in the form of sprouting, dendritic remodelling and changes in neuronal
      coding, firing and synaptic properties; elements collectively known as
      plasticity. An important approach to repair the injured CNS is therefore to
      harness, promote and refine plasticity. In the adult, this is partly limited by
      the extracellular matrix (ECM). While the ECM typically provides a supportive
      framework to CNS neurones, its role is not only structural; the ECM is
      homeostatic, actively regulatory and of great signalling importance, both
      directly via receptor or coreceptor-mediated action and via spatially and
      temporally relevant localization of other signalling molecules. In an injury or
      disease state, the ECM represents a key environment to support a healing and/or
      regenerative response. However, there are aspects of its composition which prove
      suboptimal for recovery: some molecules present in the ECM restrict plasticity
      and limit repair. An important therapeutic concept is therefore to render the ECM
      environment more permissive by manipulating key components, such as inhibitory
      chondroitin sulphate proteoglycans. In this review we discuss the major
      components of the ECM and the role they play during development and following
      brain or spinal cord injury and we consider a number of experimental strategies
      which involve manipulations of the ECM, with the aim of promoting functional
      recovery to the injured brain and spinal cord. 

PMID- 24438521
TI  - Reliability of regression-based normative data for the oral symbol digit
      modalities test: an evaluation of demographic influences, construct validity, and
      impairment classification rates in multiple sclerosis samples.
AB  - The oral Symbol Digit Modalities Test (SDMT) has been recommended to assess
      cognition for multiple sclerosis (MS) patients. However, the lack of adequate
      normative data has limited its clinical utility. Recently published regression
      based norms may resolve this limitation but, because these norms were derived
      from a relatively small sample, their stability is unclear. We aimed to evaluate
      the stability of regression-based SDMT norms by comparing existing norms to a
      cross-validation dataset. First, regression-based normative data were created
      from a similarly-sized, independent, control sample (n = 94). Next the original
      and cross-validation norms were compared for equivalency, management of
      demographic influences, construct validity, and impairment classification rates
      in a mildly affected MS sample (n = 70). Lastly, similar comparisons were made
      for a large, representative MS clinic sample (n = 354). We found construct
      validity and management of demographic influences were equivalent for the two
      sets of regression-based norms but lower T-scores were obtained using the
      original dataset, resulting in discrepancies in impairment classification. In
      conclusion, regression-based norms for the oral SDMT attenuate demographic
      influences and possess adequate construct validity. However, norms generated
      using small samples may yield unreliable classification of cognitive impairment.
      Larger, representative databases will be necessary to improve the clinical
      utility of regression-based norms. 

PMID- 24438522
TI  - Integration opportunities for HIV and family planning services in Addis Ababa,
      Ethiopia: an organizational network analysis.
AB  - BACKGROUND: Public health resources are often deployed in developing countries by
      foreign governments, national governments, civil society and the private health
      clinics, but seldom in ways that are coordinated within a particular community or
      population. The lack of coordination results in inefficiencies and suboptimal
      results. Organizational network analysis can reveal how organizations interact
      with each other and provide insights into means of realizing better public health
      results from the resources already deployed. Our objective in this study was to
      identify the missed opportunities for the integration of HIV care and family
      planning services and to inform future network strengthening. METHODS: In two sub
      cities of Addis Ababa, we identified each organization providing either HIV care
      or family planning services. We interviewed representatives of each of them about
      exchanges of clients with each of the others. With network analysis, we
      identified network characteristics in each sub-city network, such as referral
      density and centrality; and gaps in the referral patterns. The results were
      shared with representatives from the organizations. RESULTS: The two networks
      were of similar size (25 and 26 organizations) and had referral densities of
      0.115 and 0.155 out of a possible range from 0 (none) to 1.0 (all possible
      connections). Two organizations in one sub-city did not refer HIV clients to a
      family planning organization. One organization in one sub-city and seven in the
      other offered few HIV services and did not refer clients to any other HIV service
      provider. Representatives from the networks confirmed the results reflected their
      experience and expressed an interest in establishing more links between
      organizations. CONCLUSIONS: Because of organizations not working together, women
      in the two sub-cities were at risk of not receiving needed family planning or HIV
      care services. Facilitating referrals among a few organizations that are most
      often working in isolation could remediate the problem, but the overall referral
      densities suggests that improved connections throughout might benefit conditions
      in addition to HIV and family planning that need service integration.

PMID- 24438523
TI  - Recent progress in the research of small molecule HIV-1 RNase H inhibitors.
AB  - Reverse transcription of human immunodeficiency virus type 1 (HIV-1) is a crucial
      step in the life cycle initiated by the viral-coded reverse transcriptase (RT),
      functioning as RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the
      ribonuclease H (RNase H). The RNase H functions to degrade the RNA strand of the
      RNA:DNA heteroduplex, which makes it an attractive target for rational anti-HIV-1
      drug design and development. Although development of drugs targeting the DNA
      polymerase have been highly successful, the discovery of drugable inhibitors of
      HIV RNase H is still in its infancy and none of RNase H inhibitors has reached
      the clinical development stage currently. This review describes the recent
      progress in the HIV-1 RNase H inhibitors, focusing on their chemical feature,
      mechanism and the structure-activity relationship (SAR). 

PMID- 24438524
TI  - Cytotoxicity of novel sulfanilamides towards sensitive and multidrug-resistant
      leukemia cells.
AB  - Novel sulfa Schiff bases were synthesized and characterized by a reaction between
      aromatic sulfonamides and aromatic aldehydes or heterocyclic ketones in equimolar
      ratios. Their cytotoxicity was evaluated by the resazurin assay towards human
      sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Three of
      the tested compounds viz., 4-(anthracen-9-ylmethyleneamino)-N-(pyrimidin-2
      yl)benzenesulfonamide (4), 4-(anthracen-9- ylmethyleneamino)benzenesulfonamide,
      (5) and 4-((3-phenylallylidene)amino)benzene-sulfonamide, (6) were cytotoxic
      (IC50 values: 5.38-19.96 uM). CEM/ADR5000 cells were not cross-resistant to these
      compounds, indicating activity against otherwise drug-resistant tumors. Compound
      6 inhibited P-glycoprotein by increasing doxorubicin accumulation and reducing
      expression of P-glycoprotein in CEM/ADR5000 cells. A human P-glycoprotein
      homology model was used for molecular docking studies. Compound 6 and verapamil
      (a well-known P-glycoprotein inhibitor) docked with similar binding energies to
      the same binding pocket. 

PMID- 24438525
TI  - In vitro, in vivo and in silico analysis of the anticancer and estrogen-like
      activity of guava leaf extracts.
AB  - Anticancer drug research based on natural compounds enabled the discovery of many
      drugs currently used in cancer therapy. Here, we report the in vitro, in vivo and
      in silico anticancer and estrogen-like activity of Psidium guajava L. (guava)
      extracts and enriched mixture containing the meroterpenes guajadial, psidial A
      and psiguadial A and B. All samples were evaluated in vitro for anticancer
      activity against nine human cancer lines: K562 (leukemia), MCF7 (breast), NCI/ADR
      RES (resistant ovarian cancer), NCI-H460 (lung), UACC-62 (melanoma), PC-3
      (prostate), HT-29 (colon), OVCAR-3 (ovarian) and 786-0 (kidney). Psidium
      guajava's active compounds displayed similar physicochemical properties to
      estradiol and tamoxifen, as in silico molecular docking studies demonstrated that
      they fit into the estrogen receptors (ERs). The meroterpene-enriched fraction was
      also evaluated in vivo in a Solid Ehrlich murine breast adenocarcinoma model, and
      showed to be highly effective in inhibiting tumor growth, also demonstrating
      uterus increase in comparison to negative controls. The ability of guajadial,
      psidial A and psiguadials A and B to reduce tumor growth and stimulate uterus
      proliferation, as well as their in silico docking similarity to tamoxifen,
      suggest that these compounds may act as Selective Estrogen Receptors Modulators
      (SERMs), therefore holding significant potential for anticancer therapy. 

PMID- 24438526
TI  - Misfolding of apoprotein B-100, LDL aggregation and 17-beta -estradiol in
      atherogenesis.
AB  - The long quest for a missing mechanistic rationale accounting for the correlation
      between plasma cholesterol levels and cardiovascular disease (CVD) has been
      focused on various possible modifications of low density lipoprotein (LDL),
      turning this physiological cholesterol carrier into a damaging agent able to
      trigger atherogenesis and later the onset of the disease. In addition to the
      debated oxidized LDL (oxLDL), a modified LDL with a misfolded apoprotein B-100,
      called electronegative LDL(-) for its negative charge due to an increased amount
      of free fatty acids, is commonly present in plasma. LDL(-) is generated by the
      action of secretory calcium dependent phospholipase A2. LDL(-) primes LDL
      aggregation and amyloid formation according to mechanisms very similar to those
      observed in other misfolding diseases. The LDL particle aggregates recall the
      structure and size of the subendothelial lipid droplets described in early
      atherogenesis and elicit a powerful inflammatory response. The use of 17-beta
      estradiol (E2) confirmed that the suggested atherogenicity of LDL (-) is mostly
      dependent on the misfolded character of its apoprotein. E2 binding to the
      apoprotein of native LDL, through a specific and saturable receptor, inhibits
      misfolding phenomenon despite an unaffected production of LDL (-) by
      phospholipase A2, ultimately preventing LDL aggregation. The apoprotein
      misfolding in LDL(-) emerges as a possible significant trigger mechanism of
      atherogenesis. Potential implications for the development of novel therapeutic
      approaches might be hypothesized in perspective. The existing evidence is
      discussed and reported in this review. 

PMID- 24438527
TI  - Silicosis: geographic changes in research: an analysis employing density
      equalizing mapping.
AB  - BACKGROUND: A critical evaluation of scientific efforts is needed in times of
      modified evaluation criteria for academic personnel and institutions. METHODS:
      Using scientometric benchmark procedures and density-equalizing mapping, we
      analysed the global scientific efforts on "silicosis" of the last 92 years
      focusing on geographical changes within the last 30 years, specifying the most
      productive authors, institutions, countries and the most successful cooperations.
      RESULTS: The USA as the most productive supplier have established their position
      as center of international cooperation, followed in considerable distance by the
      United Kingdom, Germany and China. Asian countries, particularly China, catch up
      and are expected to excel the USA still in this decade. CONCLUSION: The
      combination of scientometric procedures with density-equalizing mapping reveals a
      distinct global pattern of research productivity and citation activity. Modified
      h-index, citationrate and impact factor have to be discussed critically due to
      distortion by bias of self-citation, language and co-authorship.

PMID- 24438528
TI  - Genetic variants conferring susceptibility to Alzheimer's disease in the general
      population; do they also predispose to dementia in Down's syndrome.
AB  - BACKGROUND: Down's syndrome (DS) is caused by either complete or partial
      triplication of chromosome 21, affecting approximately 1/1000 live births, and it
      is widely accepted that individuals with DS are more likely to develop dementia
      of Alzheimer's disease (DAD) compared with the general population. Recent
      collaborative genome-wide association studies of large case control data sets of
      individuals with and without Alzhemier's disease (AD) have revealed new risk
      variants for dementia, as well as confirming previously identified risk variants.
      In this study, nine AD-derived SNPs, near or within the CR1 (rs3818361), BIN1
      (rs744373), CD2AP (rs9349407), EPHA1 (rs11767557), CLU (rs1532278), MS4A6A/4A
      (rs610932), PICALM (rs561655), ABCA7 (rs3764650) and CD33 (rs3865444) genes were
      genotyped in 295 individuals with DS. RESULTS: There were no significant
      associations between these nine GWAS-derived SNPs and DAD in British Caucasian
      individuals with DS. Interestingly the CR1 rs3818361 variant appeared to be
      associated with mortality in our cohort, particularly in the subjects without
      dementia. To our knowledge, this is the first time that this variant has been
      implicated as a determinant of mortality and the finding warrants further
      investigation in other cohorts with DS. CONCLUSIONS: This study shows negative
      associations of nine AD-derived SNPs with DAD in DS. This may be due to the
      modest size of our cohort, which may indicate that our study is insufficiently
      powered to pick up such associations. We cannot conclusively exclude a role for
      these SNPs in DAD in DS. Clearly, efforts to investigate genetic variants with
      small effects on disease risk require a much larger cohort of individuals with
      DS. In fact, we hypothesize that a sample size of 4465 individuals with DS would
      be needed to determine the role in DAD in DS of the nine AD-derived SNPs
      investigated in this study. We therefore recommend that all national and
      international clinics with access to individuals with DS should contribute DNA
      samples to form DS consortia.

PMID- 24438530
TI  - Alterations in circadian rhythms are associated with increased lipid peroxidation
      in females with bipolar disorder.
AB  - Disturbances in both circadian rhythms and oxidative stress systems have been
      implicated in the pathophysiology of bipolar disorder (BD), yet no studies have
      investigated the relationship between these systems in BD. We studied the impact
      of circadian rhythm disruption on lipid damage in 52 depressed or euthymic BD
      females, while controlling for age, severity of depressive symptoms and number of
      psychotropic medications, compared to 30 healthy controls. Circadian rhythm
      disruption was determined by a self-report measure (Biological Rhythm Interview
      of Assessment in Neuropsychiatry; BRIAN), which measures behaviours such as
      sleep, eating patterns, social rhythms and general activity. Malondialdehyde
      (MDA) levels were measured as a proxy of lipid peroxidation. We also measured the
      activity of total and extracellular superoxide dismutase (SOD), catalase (CAT)
      and glutathione S-transferase (GST). Multiple linear regressions showed that
      circadian rhythm disturbance was independently associated with increased lipid
      peroxidation in females with BD (p < 0.05). We found decreased extracellular SOD
      (p < 0.05), but no differences in total SOD, CAT or GST activity between bipolar
      females and controls. Circadian rhythms were not associated with lipid
      peroxidation in healthy controls, where aging was the only significant predictor.
      These results suggest an interaction between the circadian system and redox
      metabolism, in that greater disruption in daily rhythms was associated with
      increased lipid peroxidation in BD only. Antioxidant enzymes have been shown to
      follow a circadian pattern of expression, and it is possible that disturbance of
      sleep and daily rhythms experienced in BD may result in decreased antioxidant
      defence and therefore increased lipid peroxidation. This study provides a basis
      for further investigation of the links between oxidative stress and circadian
      rhythms in the neurobiology of BD.

PMID- 24438529
TI  - Transcriptome profiling of granulosa cells from bovine ovarian follicles during
      atresia.
AB  - BACKGROUND: The major function of the ovary is to produce oocytes for
      fertilisation. Oocytes mature in follicles surrounded by nurturing granulosa
      cells and all are enclosed by a basal lamina. During growth, granulosa cells
      replicate and a large fluid-filled cavity (the antrum) develops in the centre.
      Only follicles that have enlarged to over 10 mm can ovulate in cows. In mammals,
      the number of primordial follicles far exceeds the numbers that ever ovulate and
      atresia or regression of follicles is a mechanism to regulate the number of
      oocytes ovulated and to contribute to the timing of ovulation. To better
      understand the molecular basis of follicular atresia, we undertook transcriptome
      profiling of granulosa cells from healthy (n = 10) and atretic (n = 5) bovine
      follicles at early antral stages (< 5 mm). RESULTS: Principal Component Analysis
      (PCA) and hierarchical classification of the signal intensity plots for the
      arrays showed primary clustering into two groups, healthy and atretic. These
      analyses and size-frequency plots of coefficients of variation of signal
      intensities revealed that the healthy follicles were more heterogeneous.
      Examining the differentially-expressed genes the most significantly affected
      functions in atretic follicles were cell death, organ development, tissue
      development and embryonic development. The overall processes influenced by
      transcription factor gene TP53 were predicted to be activated, whereas those of
      MYC were inhibited on the basis of known interactions with the genes in our
      dataset. The top ranked canonical pathway contained signalling molecules common
      to various inflammatory/fibrotic pathways such as the transforming growth factor
      beta and tumour necrosis factor-alpha pathways. The two most significant networks
      also reflect this pattern of tissue remodelling/fibrosis gene expression. These
      networks also contain molecules which are present in the canonical pathways of
      hepatic fibrosis/hepatic stellate cell activation and transforming growth factor
      beta signalling and were up regulated. CONCLUSIONS: Small healthy antral
      follicles, which have a number of growth outcomes, exhibit greater variability in
      gene expression, particularly in genes associated with cell division and other
      growth-related functions. Atresia, on the other hand, not only involves cell
      death but clearly is an active process similar to wound healing.

PMID- 24438531
TI  - The biomechanics of race walking: literature overview and new insights.
AB  - This review aims to provide both researchers and coaches with a comprehensive
      overview of race walking biomechanics and to point out new viable route for
      future analyses. The examined literature has been divided into three categories
      according to the method of analysis: kinematics, ground reaction forces and joint
      power/efficiency. From an overall view, race walking athletes seem to adhere to
      the 'straightened knee' rule, but at race speed they do not observe the 'no
      flight time' rule. The coach-oriented analysis highlights that stride length (SL)
      is more important than stride frequency (SF) for increasing speed and it is
      mainly obtained by ankle and hip joint power. Moreover, kinematic differences
      (SF, SL and flight time) between male and female athletes were shown. Also, we
      found that the maximal speed prediction according to dynamic similarity theory
      with walking (Froude number) is not applicable as the 3D trajectory of the body
      centre of mass does not follow an arc of circumference as in walking. The
      analysed literature shows some shortcomings: (1) the data collection is often
      unreliable because of the mixture of gender and performance level and (2) the
      analysis has sometimes been performed on a limited number of strides and speeds.
      These limitations lead to a scattered and incomplete gait description and a
      biased application of the results. The research strategy adopted so far is
      promising but further rigorous analyses need to be approached to obtain a fully
      comprehensive picture of race walking and to provide coaches with consistent
      results and reference values.

PMID- 24438532
TI  - High-throughput, high-content screening for novel pigmentation regulators using a
      keratinocyte/melanocyte co-culture system.
AB  - Skin pigmentation is a complex process including melanogenesis within melanocytes
      and melanin transfer to the keratinocytes. To develop a comprehensive screening
      method for novel pigmentation regulators, we used immortalized melanocytes and
      keratinocytes in co-culture to screen large numbers of compounds. High-throughput
      screening plates were subjected to digital automated microscopy to quantify the
      pigmentation via brightfield microscopy. Compounds with pigment suppression were
      secondarily tested for their effects on expression of microphthalmia
      transcription factor (MITF) and several pigment regulatory genes, and further
      validated in terms of non-toxicity to keratinocytes/melanocytes and dose
      dependent activity. The results demonstrate a high-throughput, high-content
      screening approach, which is applicable to the analysis of large chemical
      libraries using a co-culture system. We identified candidate pigmentation
      inhibitors from 4000 screened compounds including zoxazolamine, 3-methoxycatechol
      and alpha-mangostin, which were also shown to modulate expression of MITF and
      several key pigmentation factors and are worthy of further evaluation for
      potential translation to clinical use. 

PMID- 24438534
TI  - Commentary: Working memory training and ADHD - where does its potential lie?
      Reflections on Chacko et al. (2014).
AB  - Chacko et al.'s investigation of the clinical utility of WM training to alleviate
      key symptoms of ADHD is timely and substantial, and marks a significant point in
      cognitive training research. Cogmed Working Memory Training (CWMT) involves
      intensive practice on multiple memory span tasks that increase in difficulty as
      performance improves with practice. Relative to a placebo version in which the
      span level of the memory tasks are kept at a low fixed level, Chacko et al. ()
      found that CWMT boosted the performance of children with ADHD on short-term
      memory (STM) tasks similar to trained activities. Complex WM span measures
      sharing little overlap with the structure of training activities were not
      enhanced. Neither did active CWMT ameliorate classic symptoms of ADHD such as
      parent or teacher ratings of attentional problems, or direct measures of motor
      impulsivity and sustained attention. Reading, spelling, comprehension or
      mathematics scores similarly showed no response to training. 

PMID- 24438533
TI  - Hedgehog signaling pathway is a potential therapeutic target for gallbladder
      cancer.
AB  - Gallbladder cancer (GBC) is a particularly deadly type of cancer with a 5-year
      survival rate of only 10%. New effective therapeutic strategies are greatly
      needed. Recently, we have shown that Hedgehog (Hh) signaling is reactivated in
      various types of cancer and is a potential therapeutic target. However, little is
      known about the biological significance of Hh signaling in human GBC. In this
      study, we determined whether Hh signaling could be a therapeutic target in GBC.
      The Hh transcription factor Gli1 was detected in the nucleus of GBC cells but not
      in the nucleus of normal gallbladder cells. The expression levels of Sonic Hh
      (Shh) and Smoothened (Smo) in human GBC specimens (n = 37) were higher than those
      in normal gallbladder tissue. The addition of exogenous Shh ligand augmented the
      anchor-dependent and anchor-independent proliferation and invasiveness of GBC
      cells in vitro. In contrast, inhibiting the effector Smo decreased the anchor
      dependent and anchor-independent proliferation. Furthermore, the suppression of
      Smo decreased GBC cell invasiveness through the inhibition of MMP-2 and MMP-9
      expression and inhibited the epithelial-mesenchymal transition. In a xenograft
      model, tumor volume in Smo siRNA-transfected GBC cells was significantly lower
      than in control tumors. These results suggest that Hh signaling is elevated in
      GBC and may be involved in the acquisition of malignant phenotypes, and that Hh
      signaling may be a potential therapeutic target for GBC.

PMID- 24438535
TI  - Intrapelvic sciatic notch schwannoma.

PMID- 24438536
TI  - Glioma immunoenvironment.

PMID- 24438537
TI  - Role of subconcussion and repetitive TBI.

PMID- 24438538
TI  - Suboptimal compliance with evidence-based guidelines in patients with traumatic
      brain injuries.
AB  - OBJECT: Evidence-based management (EBM) guidelines for severe traumatic brain
      injuries (TBIs) were promulgated decades ago. However, the extent of their
      adoption into bedside clinical practices is not known. The purpose of this study
      was to measure compliance with EBM guidelines for management of severe TBI and
      its impact on patient outcome. METHODS: This was a retrospective study of blunt
      TBI (11 Level I trauma centers, study period 2008-2009, n = 2056 patients).
      Inclusion criteria were an admission Glasgow Coma Scale score <= 8 and a CT scan
      showing TBI, excluding patients with nonsurvivable injuries-that is, head
      Abbreviated Injury Scale score of 6. The authors measured compliance with 6
      nonoperative EBM processes (endotracheal intubation, resuscitation, correction of
      coagulopathy, intracranial pressure monitoring, maintaining cerebral perfusion
      pressure >= 50 cm H2O, and discharge to rehabilitation). Compliance rates were
      calculated for each center using multivariate regression to adjust for patient
      demographics, physiology, injury severity, and TBI severity. RESULTS: The overall
      compliance rate was 73%, and there was wide variation among centers. Only 3
      centers achieved a compliance rate exceeding 80%. Risk-adjusted compliance was
      worse than average at 2 centers, better than average at 1, and the remainder were
      average. Multivariate analysis showed that increased adoption of EBM was
      associated with a reduced mortality rate (OR 0.88; 95% CI 0.81-0.96, p < 0.005).
      CONCLUSIONS: Despite widespread dissemination of EBM guidelines, patients with
      severe TBI continue to receive inconsistent care. Barriers to adoption of EBM
      need to be identified and mitigated to improve patient outcomes.

PMID- 24438539
TI  - Hearing assessment in dental practitioners and other academic professionals from
      an urban setting.
AB  - INTRODUCTION: Extended exposure to high-speed handpieces and other noise
      intensive devices might put dentists at risk for possible hearing impairment. The
      aim of this study was to determine the hearing ability of dentists and other
      scientists for comparison. METHODS: After approval by the ethics committee, 115
      subjects (dentists and other academic professionals as controls) of both genders
      were enrolled in the study. Exclusion criteria were colds, ear-blockages or
      abnormal hearing-thresholds. An audiometric determination (Oscilla USB
      audiometer, AudioConsole 3, Inmedico A/S, Denmark) was performed in the frequency
      range of 125 Hz to 8 kHz for both ears. Anamnestic data and number of years in
      the profession were assessed using a questionnaire. Differences between groups
      were analyzed with the Mann-Whitney-U-test. RESULTS: Data from 53 dentists and 55
      other academic professionals (69.4% male, 30.6% female) with a mean age of 51.7
      +/- 9.6 years and similar gender distributions in both groups were analyzed. The
      audiometric tests for the right and left air conduction showed that the hearing
      of dentists tended to be slightly more impaired than in the control subjects. For
      the frequencies 3 kHz and 4 kHz these differences were statistically significant
      for both ears. In contrast, no significant differences were found in this range
      for bone conduction. CONCLUSIONS: Hearing impairment in dentists was slightly
      higher than in controls. Although other factors like environmental noise exposure
      were comparable for both groups, occupational exposure to high-speed handpieces
      and other noisy devices can be an additional burden for the hearing.

PMID- 24438540
TI  - Reporting outcomes of definitive radiation-based treatment for esophageal cancer:
      a review of the literature.
AB  - Accurate evaluation of radical radiotherapy requires well designed research with
      valid and appropriate outcomes. This study reviewed standards of outcome
      reporting and study design in randomized controlled trials (RCTs) of radiation
      based therapy for esophageal cancer and made recommendations for future work.
      Randomized controlled trials reporting outcomes of definitive radiation-based
      treatment alone or in combination with chemotherapy were systematically
      identified and summarized. The types, frequency, and definitions of all clinical
      and patient-reported outcomes (PROs) reported in the methods and results sections
      of papers were examined. Studies providing a definition for at least one outcome
      and presenting all outcomes reported in the methods were classified as high
      quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified.
      The primary outcome was overall survival in 13 studies, but five different
      definitions were reported. Outcomes for treatment failure included local,
      regional, and distant failures, and inconsistent definitions were applied. An
      observer assessment of dysphagia was reported in seven RCTs but PROs were
      reported in only one. Only three RCTs were at low risk of bias, with all lacking
      reports of sequence generation and only a minority reporting allocation
      concealment. The quality of outcome reporting in RCTs was inconsistent and risked
      bias. A core outcome set including clinical and PROs is needed to improve
      reporting of trials of definitive radiation-based treatment for esophageal
      cancer. 

PMID- 24438541
TI  - Recent methods for assessing osteoporosis and fracture risk.
AB  - In the management and treatment of osteoporosis, the target is to assess fracture
      risk and the end-point is to prevent fractures. Traditionally, measurement of
      bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) has been the
      standard method for diagnosing osteoporosis, in addition to assessing fracture
      risk and therapeutic effects. Quantitative computed tomography (QCT) can quantify
      volumetric BMD, and cancellous bone can be measured independently of surrounding
      cortical bone and aortic calcification. Hip structure analysis (HSA) is a method
      using the DXA scan image and provides useful data for assessing hip fracture
      risk. Recently, new tools to assess osteoporosis and fracture risk have been
      developed. One of the recent advances has been the development of the FRAX
      (Fracture Risk Assessment Tool), which is helpful in conveying fracture risk to
      patients and providing treatment guidance to clinicians. Another advance is the
      finite element (FE) method based on data from computed tomography (CT), which is
      useful for assessing bone strength, fracture risk, and therapeutic effects on
      osteoporosis. In selecting the most appropriate drug for osteoporosis treatment,
      assessment by bone metabolic markers is an important factor. In this review,
      recent patents for assessing osteoporosis and fracture risk are discussed. 

PMID- 24438542
TI  - Long-wavelength room-temperature luminescence from InAs/GaAs quantum dots with an
      optimized GaAsSbN capping layer.
AB  - An extensive study on molecular beam epitaxy growth conditions of quaternary
      GaAsSbN as a capping layer (CL) for InAs/GaAs quantum dots (QD) was carried out.
      In particular, CL thickness, growth temperature, and growth rate were optimized.
      Problems related to the simultaneous presence of Sb and N, responsible for a
      significant degradation of photoluminescence (PL), are thereby solved allowing
      the achievement of room-temperature (RT) emission. A particularly strong
      improvement on the PL is obtained when the growth rate of the CL is increased.
      This is likely due to an improvement in the structural quality of the quaternary
      alloy that resulted from reduced strain and composition inhomogeneities.
      Nevertheless, a significant reduction of Sb and N incorporation was found when
      the growth rate was increased. Indeed, the incorporation of N is intrinsically
      limited to a maximum value of approximately 1.6% when the growth rate is at 2.0
      ML s-1. Therefore, achieving RT emission and extending it somewhat beyond 1.3 MUm
      were possible by means of a compromise among the growth conditions. This opens
      the possibility of exploiting the versatility on band structure engineering
      offered by this QD-CL structure in devices working at RT. PACS: 81.15.Hi
      (molecular beam epitaxy); 78.55.Cr (III-V semiconductors); 73.21.La (quantum
      dots). 

PMID- 24438543
TI  - One-step supraclavicular approach to the treatment of Dysphagia lusoria.
AB  - A one-step supraclavicular approach for the surgical treatment of the aberrant
      right subclavian artery is described in a case of dysphagia lusoria in a 38-year
      old female. The approach allows for safe division of the arteria lusoria and its
      re-anastomosis to the common carotid artery while the patient benefits from a
      mini-invasive extrathoracic procedure. doi: 10.1111/jocs.12287 (J Card Surg
      2014;29:519-522). 

PMID- 24438545
TI  - Which fluid space is affected by ultrafiltration during hemodiafiltration?
AB  - Ultrafiltration (UF) is a common procedure performed during almost all dialysis
      sessions. During UF, several liters of fluid are removed; however, what
      proportion of this fluid is removed from which fluid space could not be
      clinically measured easily until now; we designed this study to evaluate the
      fluid spaces most affected by UF. This is a prospective cohort study of 40
      prevalent chronic hemodialysis patients receiving thrice weekly hemodiafiltration
      (HDF). We measured the patients' fluid spaces using a whole-body bioimpedance
      apparatus to evaluate the changes of fluid spaces before and immediately after
      the HDF sessions. We recorded the data on fluid spaces, UF volume, and blood
      pressures. The cohort consisted of 40 prevalent HDF patients, aged 60.0 +/- 5.2
      years (37.5% men; 27.5% people with diabetes), and body weight 71.03 +/- 15.48
      kg. Achieved UF was 2.38 +/- 0.98 L on HDF (measured fluid overload: 2.35 +/-
      1.44 L). The extracellular fluid (EC) volume decreased from 16.84 +/- 3.52 to
      14.89 +/- 3.06 L (P < 0.0001) and intracellular fluid (IC) volume from 16.88 +/-
      4.40 to 16.55 +/- 4.48 L (P = 0.45). Although urea volume of distribution
      remained effectively unchanged (31.38 +/- 7.28 vs. 30.70 +/- 7.32 L; P = 0.45),
      the degree of EC volume overload decreased from 13.60% +/- 7.30% to 3.83% +/-
      8.32% (P < 0.0001). The mean arterial pressure also decreased from 122.95 +/-
      19.02 to 108.50 +/- 13.91 mmHg (P < 0.0001). We conclude that source of net fluid
      loss by ultrafiltration is almost exclusively the EC fluid space. The
      intracellular fluid space is not significantly affected immediately after HDF.

PMID- 24438544
TI  - Multiplex genomic structure variation mediated by TALEN and ssODN.
AB  - BACKGROUND: Genomic structure variation (GSV) is widely distributed in various
      organisms and is an important contributor to human diversity and disease
      susceptibility. Efficient approaches to induce targeted genomic structure
      variation are crucial for both analytic and therapeutic studies of GSV. Here, we
      presented an efficient strategy to induce targeted GSV including chromosomal
      deletions, duplications and inversions in a precise manner. RESULTS: Utilizing
      Transcription Activator-Like Effector Nucleases (TALEN) designed to target two
      distinct sites, we demonstrated targeted deletions, duplications and inversions
      of an 8.9 Mb chromosomal segment, which is about one third of the entire
      chromosome. We developed a novel method by combining TALEN-induced GSV and single
      stranded oligodeoxynucleotide (ssODN) mediated gene modifications to reduce
      unwanted mutations occurring during the targeted GSV using TALEN or Zinc finger
      nuclease (ZFN). Furthermore, we showed that co-introduction of TALEN and ssODN
      generated unwanted complex structure variation other than the expected
      chromosomal deletion. CONCLUSIONS: We demonstrated the ability of TALEN to induce
      targeted GSV and provided an efficient strategy to perform GSV precisely.
      Furthermore, it is the first time to show that co-introduction of TALEN and ssODN
      generated unwanted complex structure variation. It is plausible to believe that
      the strategies developed in this study can be applied to other organisms, and
      will help understand the biological roles of GSV and therapeutic applications of
      TALEN and ssODN.

PMID- 24438546
TI  - A model for transport of a viral membrane protein through the early secretory
      pathway: minimal sequence and endoplasmic reticulum lateral mobility
      requirements.
AB  - Viral movement proteins exploit host endomembranes and the cytoskeleton to move
      within the cell via routes that, in some cases, are dependent on the secretory
      pathway. For example, melon necrotic spot virus p7B, a type II transmembrane
      protein, leaves the endoplasmic reticulum (ER) through the COPII-dependent Golgi
      pathway to reach the plasmodesmata. Here we investigated the sequence
      requirements and putative mechanisms governing p7B transport through the early
      secretory pathway. Deletion of either the cytoplasmic N-terminal region (CR) or
      the luminal C-terminal region (LR) led to ER retention, suggesting that they are
      both essential for ER export. Through alanine-scanning mutagenesis, we identified
      residues in the CR and LR that are critical for both ER export and for viral cell
      to-cell movement. Within the CR, alanine substitution of aspartic and proline
      residues in the DSSP beta-turn motif (D7 AP10 A) led to movement of discrete
      structures along the cortical ER in an actin-dependent manner. In contrast,
      alanine substitution of a lysine residue in the LR (K49 A) resulted in a
      homogenous ER distribution of the movement protein and inhibition of ER-Golgi
      traffic. Moreover, the ability of p7B to recruit Sar1 to the ER membrane is lost
      in the D7 AP10 A mutant, but enhanced in the K49 A mutant. In addition,
      fluorescence recovery after photobleaching revealed that K49 A but not D7 AP10 A
      dramatically diminished protein lateral mobility. From these data, we propose a
      model whereby the LR directs actin-dependent mobility toward the cortical ER,
      where the cytoplasmic DSSP beta-turn favors assembly of COPII vesicles for export
      of p7B from the ER. 

PMID- 24438547
TI  - Relationship among attention-deficit hyperactivity disorder, dietary behaviours
      and obesity.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most
      common psychiatric disorders of childhood and can be associated with obesity. The
      aim of this study was to reveal the connection between ADHD symptoms, food habits
      and obesity. METHODS: We examined 12 350 children (6010 boys, 6340 girls) from 27
      elementary schools in Cheonan, the Republic of Korea. The study subjects were 5-
      to 13-year-old children (9.4 +/- 1.7 years). Parents completed the DuPaul ADHD
      Rating Scale. Food habits were measured by a questionnaire adapted from the Korea
      Youth Risk Behavior Web-based Survey and a validated mini-dietary assessment
      tool. The full set of hypothesized associations was tested using covariance
      structural modelling. RESULTS: The prevalence of ADHD was 7.6% and that of
      obesity was 4.5% in our study population. The data was well fit by the model.
      ADHD was associated with body mass index (BMI; standardized beta = 0.086, P <
      0.001). Bulimic dietary behaviours was related to BMI (standardized beta = 0.548,
      P < 0.001). Socio-economic status was associated with BMI (standardized beta = 
      0.017, P = 0.027). CONCLUSION: Our analysis suggested that ADHD was a risk factor
      for obesity through dietary behavioural change and socio-economic status.

PMID- 24438552
TI  - Massive and submassive pulmonary embolism: diagnostic challenges and thrombolytic
      therapy.

PMID- 24438551
TI  - Career perspective: Paolo Cerretelli.
AB  - This article is an autobiographical account of my career as a human physiologist.
      I have spent 55 years traversing mountains, continents, seas, and skies, carrying
      out research in the laboratories of several international institutions as well as
      in the field. My scientific roots, approach to the mountains and altitude
      populations, both in Europe and in Asia, together with an account of my
      experimental studies at altitude, including extreme conditions, shall be
      presented together with pertinent occasional reflections of a personal nature. 

PMID- 24438553
TI  - Esophageal anastomosis.
AB  - This review gives an overview of the esophageal anastomosis. The history, various
      techniques and substitution organs, their advantages and disadvantages, healing
      mechanism, complications, and actual trend of this essential part of esophageal
      surgery are described. The history of the esophageal anastomosis extending from
      the first anastomosis in 1901 to today has undergone more than one century. In
      the early days, the success rate of the anastomosis was extremely low. As the
      technology progressed, the anastomosis got significant achievement. Various
      anastomotic techniques are currently being used. However, controversies exist on
      the choice of anastomotic method concerning the success rate, postoperative
      complication and quality of life. How to choose the method, no one can give the
      best answer. We searched the manuscripts about the esophageal anastomoses in
      recent years and studied the controversy questions about the anastomosis.
      Performing an esophageal anastomosis is a technical matter, and suture healing is
      independent of the patient's biologic situation. Every anastomosis technique has
      its own merit, but the outcomes were different if it was performed by different
      surgeons, and we also found that the complication rate of the anastomosis was
      mainly associated with the surgeons. So the surgeons should learn from their
      previous experience and others to avoid technical errors. 

PMID- 24438554
TI  - Effect of nosocomial bloodstream infections on mortality, length of stay, and
      hospital costs in older adults.
AB  - OBJECTIVES: To quantify the effect of nosocomial bloodstream infection (BSI) on
      older adults, including mortality, length of stay (LOS), and costs attributed to
      BSI. DESIGN: Retrospective cohort study. SETTING: Eight acute care hospitals (7
      community hospitals and 1 tertiary university-affiliated facility) belonging to
      the Duke Infection Control Outreach Network (DICON) from the states of North
      Carolina and Virginia. PARTICIPANTS: Elderly patients over 65 years of age.
      MEASUREMENTS: A multistate, multicenter, matched, retrospective cohort study was
      conducted from January 1994 through June 2002 in eight hospitals from the
      Southern-Central United States. Patients aged >65 years with nosocomial BSI were
      enrolled. Controls without bloodstream infection were matched to cases. Outcomes
      during the 90-day period following hospital discharge were evaluated to determine
      the association between BSI and mortality, hospital costs, and LOS. RESULTS:
      Eight-hundred thirty cases and 830 matched controls were identified, all with a
      mean age of 74.4 years. Among cases, 81% of BSIs were central line-associated and
      Staphylococcus aureus was the most common pathogen accounting for 34.6% of
      infections (2/3 were methicillin resistant). The mortality rate of cases was
      49.4%, compared to 33.2% for controls (OR = 2.1, P < .001), LOS was 29.2 days for
      cases and 20.2 days for controls (P < .001), and hospital charges were $102,276
      for cases compared to $69,690 for controls (P < .001). The mean LOS and mean
      costs attributable to BSI were 10 days and $43,208, respectively. CONCLUSION:
      Nosocomial BSI in older adults was significantly associated with increases in 90
      day mortality, increased LOS, and increased costs of care. Preventive
      interventions to eliminate nosocomial BSIs in older adults would likely be cost
      effective.

PMID- 24438555
TI  - Determinants of eating behaviour in university students: a qualitative study
      using focus group discussions.
AB  - BACKGROUND: College or university is a critical period regarding unhealthy
      changes in eating behaviours in students. Therefore, the purpose of this study
      was to explore which factors influence Belgian (European) university students'
      eating behaviour, using a qualitative research design. Furthermore, we aimed to
      collect ideas and recommendations in order to facilitate the development of
      effective and tailored intervention programs aiming to improve healthy eating
      behaviours in university students. METHODS: Using a semi-structured question
      guide, five focus group discussions have been conducted consisting of 14 male and
      21 female university students from a variety of study disciplines, with a mean
      age of 20.6 +/- 1.7 yrs. Using Nvivo9, an inductive thematic approach was used
      for data analysis. RESULTS: After the transition from secondary school to
      university, when independency increases, students are continuously challenged to
      make healthful food choices. Students reported to be influenced by individual
      factors (e.g. taste preferences, self-discipline, time and convenience), their
      social networks (e.g. (lack of) parental control, friends and peers), physical
      environment (e.g. availability and accessibility, appeal and prices of food
      products), and macro environment (e.g. media and advertising). Furthermore, the
      relationships between determinants and university students' eating behaviour
      seemed to be moderated by university characteristics, such as residency, student
      societies, university lifestyle and exams. Recommendations for university
      administrators and researchers include providing information and advice to
      enhance healthy food choices and preparation (e.g. via social media), enhancing
      self-discipline and self-control, developing time management skills, enhancing
      social support, and modifying the subjective as well as the objective campus food
      environment by e.g. making healthy foods price-beneficial and by providing
      vending machines with more healthy products. CONCLUSIONS: This is the first
      European study examining perceived determinants of eating behaviour in university
      students and collecting ideas and recommendations for healthy eating
      interventions in a university specific setting. University characteristics
      (residency, exams, etc.) influence the relationships between individual as well
      as social environmental determinants and university students' eating behaviour,
      and should therefore be taken into account when designing effective and tailored
      multilevel intervention programs aiming to improve healthy eating behaviours in
      university students.

PMID- 24438556
TI  - When incentives work too well: locally implemented pay for performance (P4P) and
      adverse sanctions towards home birth in Tanzania - a qualitative study.
AB  - BACKGROUND: Despite limited evidence of its effectiveness, performance-based
      payments (P4P) are seen by leading policymakers as a potential solution to the
      slow progress in reaching Millennium Development Goal 5: improved maternal
      health. This paper offers insights into two of the aspects that are lacking in
      the current literature on P4P, namely what strategies health workers employ to
      reach set targets, and how the intervention plays out when implemented by local
      government as part of a national programme that does not receive donor funding.
      METHODS: A total of 28 in-depth interviews (IDIs) with 25 individuals were
      conducted in Mvomero district over a period of 15 months in 2010 and 2011, both
      before and after P4P payments. Seven facilities, including six dispensaries and
      one health centre, were covered. Informants included 17 nurses, three clinical
      officers, two medical attendants, one lab technician and two district health
      administrators. RESULTS: Health workers reported a number of strategies to
      increase the number of deliveries at their facility, including health education
      and cooperation with traditional health providers. The staff at all facilities
      also reported that they had told the women that they would be sanctioned if they
      gave birth at home, such as being fined or denied clinical cards and/or
      vaccinations for their babies. There is a great uncertainty in relation to the
      potential health impacts of the behavioural changes that have come with P4P, as
      the reported strategies may increase the numbers, but not necessarily the
      quality. Contrary to the design of the P4P programme, payments were not based on
      performance. We argue that this was due in part to a lack of resources within the
      District Administration, and in part as a result of egalitarian fairness
      principles. CONCLUSIONS: Our results suggest that particular attention should be
      paid to adverse effects when using external rewards for improved health outcomes,
      and secondly, that P4P may take on a different form when implemented by local
      implementers without the assistance of professional P4P specialists.

PMID- 24438557
TI  - TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.
AB  - TMEPAI/PMEPA1 is a transmembrane protein that was originally identified as a
      prostatic RNA, the synthesis of which is induced by testosterone or its
      derivatives. We have recently identified TMEPAI as a direct target gene of
      transforming growth factor-beta (TGF-beta)/Smad signaling that participates in
      negative feedback control of the duration and intensity of TGF-beta/Smad
      signaling. TMEPAI is constitutively and highly expressed in many types of cancer
      and is associated with poor prognosis. Here, we report that TMEPAI is highly
      expressed in the lung adenocarcinoma cell lines Calu3, NCI-H23, and RERF-LC-KJ.
      Expression of TMEPAI in these cancer cells was significantly suppressed by a TGF
      beta receptor kinase antagonist, SB208, and by TGF-beta neutralizing antibodies.
      These results suggest that constitutive expression of TMEPAI in these cancer
      cells depends on autocrine TGF-beta stimulation. Knockdown of TMEPAI in Calu3 and
      NCI-H23 cells enhanced levels of Smad2 phosphorylation and significantly
      suppressed cell proliferation in the presence of TGF-beta, indicating that highly
      expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells
      and reduces the growth inhibitory effects of TGF-beta/Smad signaling.
      Furthermore, knockdown of TMEPAI in Calu3 and NCI-H23 cells suppressed sphere
      formation in vitro and tumor formation in s.c. tissues and in lungs after tail
      vein injection in NOD-SCID mice in vivo. Together, these experiments indicate
      that TMEPAI promotes tumorigenic activities in lung cancer cells. 

PMID- 24438558
TI  - The enigma of the dog mummy from ancient Egypt and the origin of 'Rhipicephalus
      sanguineus'.
AB  - BACKGROUND: Ticks belonging to the Rhipicephalus sanguineus group are amongst the
      most important vectors of pathogenic microorganisms to dogs and humans. However,
      the taxonomy of this species group is still the subject of debate, especially
      because there is no type specimen or reliable morphological description for
      Rhipicephalus sanguineus sensu stricto. Recently, a comprehensive morphological
      and genetic study on representative tick specimens from Europe, Africa, Americas,
      and Oceania, revealed the existence of at least four morphologically and
      genetically distinct species under the name 'R. sanguineus' infesting dogs from
      different countries. METHODS: Herein, we examined morphologically tick specimens
      retrieved on a dog mummy from Ancient Egypt (ca. 1st century - 4th century A.D.).
      The dog mummy and associated ticks were found during an archaeological expedition
      conducted in El Deir. RESULTS: Scanning electron micrographs allowed us to assess
      their identity as belonging to the R. sanguineus group. In addition on the basis
      of the scutal punctation pattern, spiracular plates, width of dorsal tail of
      spiracular plates relative to the adjacent festoon, female genital aperture, male
      adanal plates and accessory shields, these ticks were tentatively identified as
      Rhipicephalus sp. II (=temperate species). CONCLUSIONS: It can be concluded that
      R. sanguineus group ticks have infested dogs living in the Mediterranean region
      since ancient times. This finding represents the oldest record of ticks on any
      animal species and adds a new piece in the complex puzzle regarding tick
      parasitism on dogs and humans and their role as vectors of pathogens.

PMID- 24438559
TI  - The serotonin transporter polymorphism (5-HTTLPR) and personality: response style
      as a new endophenotype for anxiety.
AB  - Although the serotonin transporter length polymorphic region (5-HTTLPR)
      polymorphism is an extensively-investigated genetic marker of anxiety related
      personality traits (neuroticism and harm avoidance) and affective disorders,
      effect sizes in meta-analyses are small, if present at all, and all available
      primary studies to date lack mandatory statistical power. Moreover, questionnaire
      data is prone to confounding by variables such as social desirability. Therefore,
      extreme response style (ERS) is suggested as a new approach to elucidate the
      relationship between 5-HTTLPR and negative emotionality, as it is more implicit
      and of high reliability. N = 1075 healthy subjects were genotyped for 5-HTTLPR
      and a flanking polymorphism (rs25531) and filled out the NEO Five Factor
      Inventory and the Temperament Character Inventory. As dependent variable the
      number of extreme responses across all items was calculated. Using the common
      genotype or the triallelic approach (including rs25531) the meta-analytic
      findings could not be replicated. However, there was a significant association
      between 5-HTTLPR and extreme response style. Carriers of the L-allele or the L'
      allele, respectively, had a significantly higher number of extreme responses than
      homozygous SS carriers across all items of the NEO Five Factor Inventory. This
      finding could be replicated in an alternative personality questionnaire
      (Affective Neuroscience Personality Scales, ANPS). There is a long tradition in
      psychological assessment indicating that ERS is an implicit measure of
      personality. Given the positive findings of the present study, ERS qualifies as a
      promising endophenotype in future genetic association studies on personality and
      affective disorders.

PMID- 24438560
TI  - Effects of demand-side financing on utilisation, experiences and outcomes of
      maternity care in low- and middle-income countries: a systematic review.
AB  - BACKGROUND: Demand-side financing, where funds for specific services are
      channelled through, or to, prospective users, is now employed in health and
      education sectors in many low- and middle-income countries. This systematic
      review aimed to critically examine the evidence on application of this approach
      to promote maternal health in these settings. Five modes were considered:
      unconditional cash transfers, conditional cash transfers, short-term payments to
      offset costs of accessing maternity services, vouchers for maternity services,
      and vouchers for merit goods. We sought to assess the effects of these
      interventions on utilisation of maternity services and on maternal health
      outcomes and infant health, the situation of underprivileged women and the
      healthcare system. METHODS: The protocol aimed for collection and synthesis of a
      broad range of evidence from quantitative, qualitative and economic studies.
      Nineteen health and social policy databases, seven unpublished research databases
      and 27 websites were searched; with additional searches of Indian journals and
      websites. Studies were included if they examined demand-side financing
      interventions to increase consumption of services or goods intended to impact on
      maternal health, and met relevant quality criteria. Quality assessment, data
      extraction and analysis used Joanna Briggs Institute standardised tools and
      software. Outcomes of interest included maternal and infant mortality and
      morbidity, service utilisation, factors required for successful implementation,
      recipient and provider experiences, ethical issues, and cost-effectiveness.
      Findings on Effectiveness, Feasibility, Appropriateness and Meaningfulness were
      presented by narrative synthesis. RESULTS: Thirty-three quantitative studies, 46
      qualitative studies, and four economic studies from 17 countries met the
      inclusion criteria. Evidence on unconditional cash transfers was scanty. Other
      demand-side financing modes were found to increase utilisation of maternal
      healthcare in the index pregnancy or uptake of related merit goods. Evidence of
      effects on maternal and infant mortality and morbidity outcomes was insufficient.
      Important implementation aspects include targeting and eligibility criteria,
      monitoring, respectful treatment of beneficiaries, suitable incentives for
      providers, quality of care and affordable referral systems. CONCLUSIONS: Demand
      side financing schemes can increase utilisation of maternity services, but
      attention must be paid to supply-side conditions, the fine-grain of
      implementation and sustainability. Comparative studies and research on health
      impact and cost-effectiveness are required.

PMID- 24438561
TI  - Changes in maxillary incisor dental pulp blood flow during intrusion by mini
      implants.
AB  - AIM: The aim of this clinical study was to identify changes in pulpal blood flow
      (PBF) in human central incisors resulting from short- and long-term intrusive
      orthodontic forces from mini-implants. MATERIALS AND METHODS: A total of 40 sound
      upper central and lateral incisors in 20 patients scheduled for intrusion for
      orthodontic reasons were divided into two groups. From each group, 20 teeth were
      subjected to intrusive force from mini-implants (Group 1 = Light Force: 40 g;
      Group 2 = Heavy Force: 120 g), whereas the remaining 20 contralateral teeth were
      not subjected to forces from mini-implants and served as controls. Laser-Doppler
      flowmetry (LDF) measurements were recorded at baseline and at 3 days and 3 weeks
      following intrusion. RESULTS: PBF decreased significantly at 3 days (Light Force
      Group: 7.72 +/- 0.50; Heavy Force Group: 7.72 +/- 0.52) and then increased
      towards baseline at 3 weeks (Light Force Group: 10.37 +/- 0.58; Heavy Force
      Group: 10.31 +/- 0.45) following intrusion. CONCLUSIONS: In other words, despite
      slight regressive changes in pulpal tissue in the short-term, PBF improved after
      3 weeks following intrusion by mini-implants, indicating that the changes
      observed in PBF is reversible, even following radical incisor intrusion.

PMID- 24438562
TI  - [Alveolar bone loss in nuclear families of aggressive periodontitis and the
      heredity of root shape].
AB  - OBJECTIVE: To evaluate the status of residual alveolar bone in aggressive
      periodontitis (AgP) nuclear families and to investigate the influence of teeth
      with root abnormity on residual alveolar bone and the heredity of root abnormity,
      the premolar cone-root and proportion of crown and root. METHODS: Nineteen AgP
      probands (9 males and 10 females) at average age of 24.5 and 38 parents at
      average age 51.0 were included. A full set of periapical radiographs of all the
      subjects were taken. The residual alveolar bone of each tooth was measured by the
      ratio (shown as percentage) of the distance between apical and the alveolar bone
      crest to the whole root length. The abnormity of roots was detected on a full set
      of periapical radiographs. All the roots and crowns of teeth were measured. The
      relationship between the residual bone and the ratio was studied. The heredity
      grade of the premolar cone-root, proportion of crown and root, and root abnormity
      were computed. RESULTS: The average residual alveolar bone of probands was less
      than that of their parents.In 11 families, the father's residual alveolar bone
      was less than that of the mother's. The average residual alveolar bone of the
      teeth with root abnormity was less than that of normal teeth. The average
      residual alveolar bone of the teeth with abnormity of roots and the normal teeth
      were (67.5 +/- 22.2)% and (73.1 +/- 18.7)% respectively, with statistical
      significance (P < 0.001). The heredity grade of the premolar cone-root was 40.1%,
      the heredity grade of proportion of crown and root was 46.8%, the heredity grade
      of root abnormity was 30.3%. CONCLUSIONS: The residual alveolar bone of the teeth
      with root abnormity was less than that of normal teeth in nuclear families. The
      heritability of the root abnormity, the cone-root and proportion of crown and
      root in our sample was 0.3-0.5, which means that genetic factors accounted for
      about one third to half of the efficiency for AgP.

PMID- 24438563
TI  - [Preliminary study on measuring interdental papilla height and thickness of the
      maxillary anterior teeth based on cone-beam computed tomography].
AB  - OBJECTIVE: To investigate the features of the fill of interdental spaces by
      gingival papillae and the associated factors. METHODS: Fifteen volunteers with
      healthy gingiva were involved in this study. The height and thickness on the
      alveolar crest level of 62 maxillary anterior papilla were measured
      radiographically with cone-beam computed tomography (CBCT) scans. A standardized
      periodontal probe with Williams markings was used for measurements of the papilla
      width on the alveolar crest level. RESULTS: When the papilla was complete fill
      interdentally, the mean height of papillary tissue on the alveolar crest level
      (equal to contact point-bone crest) was (3.67 +/- 0.51) mm. The mean thickness of
      papilla on the alveolar crest level was (8.38 +/- 0.75) mm. The papilla height
      had a positive correlation with papilla thickness (r = 0.433, P < 0.001).
      CONCLUSIONS: The cone-beam computed tomography can be used for clear
      visualization of the papilla profile and the measurements of papilla height and
      thickness. Thicker and wider tissue was associated with an increased likelihood
      of having a complete papilla fill.

PMID- 24438564
TI  - [Plate related complication after mandibular reconstruction].
AB  - OBJECTIVE: To evaluate the complications and factors associated with titanium
      plates in mandibular reconstruction with different methods. METHODS: A
      retrospective analysis of 660 patients who received primary reconstruction of the
      mandible was conducted. The characters of the mandibular defect and methods of
      reconstruction were recorded. The complications and factors associated with the
      reconstruction were analyzed. RESULTS: The majority of mandibular defect was in a
      shape of L (n = 324 ). The total complication rate was 14.7% (97/660), which
      included screw loosening 5.8% (38/660), plate fracture 3.3% (22/660), plate
      exposure 3.8% (25/660), infection 7.4% (49/660) and malunion or ununion 2.9%
      (19/660). The mandibular defects reconstructed by reconstructive plates had a
      higher complication rate than that by bone grafts. The complication rate was
      10.8% (63/586) in cases reconstructed by bone grafts with miniplates. The
      complications were associated with radiation therapy and diabetes. Radiation
      therapy had a significant effect on plate exposure. CONCLUSIONS: Reconstruction
      with bone grafts can minimize the rate of plate related complication. The
      complications were associated with radiation therapy and diabetes.

PMID- 24438565
TI  - [Protein structure prediction of the lactate dehydrogenase of Streptococcus
      oligofermentans].
AB  - OBJECTIVE: To compare the gene sequence and protein structure of lactate
      dehydrogenase (LDH) in Streptococcus oligofermentans with those of other bacteria
      with different acid generating capacities in oral cavity and to analyze the
      differences of their LDH. METHODS: LDH gene sequence of Streptococcus
      oligofermentans was measured by Institute of Microbiology, Chinese Academy of
      Sciences. LDH gene sequences of four Streptococcus and Lactobacillus casei in the
      NCBI Genbank was identified and compared among the six bacteria's LDH gene
      sequences and amino acid sequences by BLAST software. ExPASy database was used to
      predict the physical-chemical characteristics, secondary structure, trans
      membrane regions, and spatial structure of Streptococcus oligofermentans LDH
      protein, which was compared with those of other bacteria. RESULTS: The full
      length of the LDH gene sequences of Streptococcus oligofermentans was 987 base
      pairs. The highest similarity was 89% with that of the Streptococcus sanguis, and
      81% similarity with Streptococcus mutans, and 70% similarity with Lactobacillus
      casei. LDH amino acid sequence of Streptococcus oligofermentans was similar to
      Streptococcus sanguinis, with the highest similitude of 96%, with a similitude of
      81% to Streptococcus mutans, but differed greatly from that of Lactobacillus
      casei, with a similitude of only 66%. Streptococcus oligofermentans LDH protein's
      physical-chemical characteristics, trans-membrane region's numbers, proportions
      of secondary structure, structural domain's location resembled those of
      Streptococcus mutans, Streptococcus sanguinis and Lactobacillus casei. Spatial
      structure differences between the LDH of Streptococcus oligofermentans and that
      of Streptococcus mutans and Lactobacillus casei were distinct. CONCLUSIONS:
      Streptococcus oligofermentans LDH's gene sequence, amino acid sequence, and
      spatial structure all vary from those of Streptococcus mutans and Lactobacillus
      casei, and these differeces may be a inherent reason that lead to the changes of
      its LDH's biological functions and incapacity of producing lactic acid.

PMID- 24438566
TI  - [Class III surgical patients facilitated by accelerated osteogenic orthodontic
      treatment].
AB  - OBJECTIVE: To evaluate the treatment time and the anterior and posterior teeth
      movement pattern as closing extraction space for the Class III surgical patients
      facilitated by accelerated osteogenic orthodontic treatment. METHODS: There were
      10 skeletal Class III patients in accelerated osteogenic orthodontic group (AOO)
      and 10 patients in control group. Upper first premolars were extracted in all
      patients. After leveling and alignment (T2), corticotomy was performed in the
      area of maxillary anterior teeth to accelerate space closing.Study models of
      upper dentition were taken before orthodontic treatment (T1) and after space
      closing (T3). All the casts were laser scanned, and the distances of the movement
      of incisors and molars were digitally measured. The distances of tooth movement
      in two groups were recorded and analyzed. RESULTS: The alignment time between two
      groups was not statistically significant. The treatment time in AOO group from T2
      to T3 was less than that in the control group (less than 9.1 +/- 4.1 months). The
      treatment time in AOO group from T1 to T3 was less than that in the control group
      (less than 6.3 +/- 4.8 months), and the differences were significant (P < 0.01).
      Average distances of upper incisor movement (D1) in AOO group and control group
      were (2.89 +/- 1.48) and (3.10 +/- 0.95) mm, respectively. Average distances of
      upper first molar movement (D2) in AOO group and control group were (2.17 +/-
      1.13) and (2.45 +/- 1.04) mm, respectively.No statistically significant
      difference was found between the two groups (P > 0.05). CONCLUSIONS: Accelerated
      osteogenic orthodontic treatment could accelerate space closing in Class III
      surgical patients and shorten preoperative orthodontic time. There were no
      influence on the movement pattern of anterior and posterior teeth during pre
      surgical orthodontic treatment.

PMID- 24438567
TI  - [Establishment of the craniofacial three-dimensional finite element models with
      the sutures defined alone].
AB  - OBJECTIVE: To develop a child craniofacial three-dimensional (3D) finite element
      model (FEM) with sutures defined alone. METHODS: The CT data for this study was
      developed from sequential computed tomography scan images taken at 0.625 mm
      intervals of an 8 years children skull. Data set was imported into Mimics 10.0
      and processed with Geomagic 9.0, and exported as initial graphics exchange
      specification(IGES) files. The IGES files were then imported into Ansys 13.0 to
      set up two FEM with or without the median palatine suture being opened. The FEM
      contained nine craniofacial sutures and eight teeth which were defined alone.For
      simulating orthopedic maxillary protraction, three forces (F1-F2) were loaded on
      FEM.F1(1 N) was loaded at 1 cm above the geison. F2(1 N) was loaded at articular
      fossa of temporal bone. F3(2 N) was directed anteriorly and paralleled with
      occlusal plane near the canine. The stress distribution and the values
      distributed in each point gained in the two models were compared. RESULTS: Two
      craniofacial 3D FEM of the child were developed with the median palatine suture
      opened or not .With median palatine suture being opened or not, the two models
      showed the similar von Mises stresses (VMS). The distribution of the VMS was in
      the bridge of the nose and dextro-ala nasi.When the median palatine suture was
      opened, the max VMS value was 18916.00*10(-4) MPa which appeared in the nose
      point and the min VMS value was 1.61*10(-4) MPa which appeared in the maxillary
      central incisor point. At the same time, the max stress value at the direction Y
      was -3985.30*10(-4) MPa and appeared in the frontomaxillary suture point, and the
      min Y value was 0.08*10(-4) MPa which appeared in the maxillary central incisor
      point. When the median palatine suture was not opened, the max VMS value was 19
      244.00*10(-4) MPa and appeared in the nose point. The min VMS value was 1.62*10(
      4) MPa and appeared in the maxillary central incisor point. At the same time, the
      max stress value at the direction Y was -4258.20*10(-4) MPa and appeared in the
      frontomaxillary suture point, and the min Y value was 0.08*10(-4) MPa which
      appeared in the maxillary central incisor point. CONCLUSIONS: To define the
      sutures as entities alone contributed to develop child craniofacial 3D FEM which
      consist nine sutures. There was tiny difference in stress distribution in both
      the VMS and in Y direction with the median palatine suture being opened or not.

PMID- 24438568
TI  - [Expression of secretoglobin family 2A member 2 in oral lichen planus lesions].
AB  - OBJECTIVE: To examine the expression of secretoglobin family 2A member 2
      (SCGB2A2) (mammaglobin A, MGB1) in oral lichen planus (OLP) lesions. METHODS:
      Sixteen OLP patients and 10 healthy controls were included in this study. The
      real time reverse transcription-PCR (RT-PCR), Western blotting and
      immunohistochemistry (IHC) were used to determine the mRNA and protein of
      SCGB2A2. RESULTS: Compared with healthy controls (0.48 +/- 0.09), the expression
      of SCGB2A2 protein in OLP lesions significantly increased (1.02 +/- 0.11) (P <
      0.05).However, the mRNA level of SCGB2A2 in lesions was significantly lower than
      that in controls (P < 0.05). CONCLUSIONS: These results suggest that SCGB2A2 may
      be involved in pathogenesis of OLP.

PMID- 24438569
TI  - [Clinical research on curative effect of complete denture with two kinds of
      occlusion for temporomandibular joint disorders of aged edentulous patients].
AB  - OBJECTIVE: To compare curative effect between complete denture with lingualized
      occlusion and anatomic occlusion on temporomandibular joint disorders (TMD) of
      aged edentulous patients with severe residual alveolar ridge resorption. METHODS:
      Seventy aged edentulous patients with severe residual alveolar ridge resorption
      were recruited in this study and randomly assigned into two groups, thirty-five
      each. In Group A, patients received complete denture with lingualized occlusion,
      and in Group B, patients received complete denture with anatomic occlusion. The
      condition of TMD was examined and recorded by the same TMD specialist at
      baseline, 3 months and 6 months following denture delivery. The recovery effect
      of TMD was evaluated according to Fricton Index. Related data were analyzed
      statistically with t-test and rank sum test. RESULTS: Three months following
      denture delivery, the craniomandibular index (CMI) decrease value was (0.064 +/-
      0.022) in group A, and was significantly higher than that in group B (0.043 +/-
      0.018) (P < 0.01). Six months following denture delivery, the CMI decrease value
      was (0.084 +/- 0.020) in group A, and was significantly higher than that in group
      B (0.070 +/- 0.021) (P = 0.011<0.05). CONCLUSIONS: Complete denture with
      lingualized occlusion may be more conducive to the remission of TMD for aged
      edentulous patients with severe residual alveolar ridge resorption.

PMID- 24438570
TI  - [Role of p38 mitogen activated protein kinase on cyclic stretch in human facial
      hypertrophic scar fibroblasts differentiation into myofibroblasts].
AB  - OBJECTIVE: To explore the signal transduction mechanism of p38 mitogen activated
      protein kinase (p38MAPK) in human facial hypertrophic scar fibroblast (FB)
      differentiation into myofibroblasts (MFB). METHODS: Fibroblasts of primary
      culture were simple randomly assigned into two groups: cyclic stretch (control
      group) and cyclic stretch pre-treated with SB203580(experimental group).
      Expression of P-p38MAPK and alpha-smooth muscle actin (alpha-SMA) protein were
      examined using Western blotting and expression of transforming growth factor
      beta1 (TGF-beta1) mRNA and alpha-SMA mRNA were examined using reverse
      transcription PCR (RT-PCR). RESULTS: In control group, the expressions of alpha
      SMA, p38MAPK, TGF-beta1 mRNA and alpha-SMA mRNA (0 h: 0.134 +/- 0.011, 0.239 +/-
      0.015, 0.214 +/- 0.018, 0.252 +/- 0.010; 6 h: 0.152 +/- 0.014, 0.287 +/- 0.016,
      0.288 +/- 0.011, 0.277 +/- 0.013; 12 h: 0.172 +/- 0.017, 0.320 +/- 0.017, 0.335
      +/- 0.013, 0.297 +/- 0.006) , were significantly increased with loading time (6
      h>0 h; 12 h>0 and 6 h). In experimental group (pre-treated with SB203580), the
      expressions of alpha-SMA, p38MAPK, TGF-beta1 mRNA,alpha-SMA mRNA (6 h: 0.116 +/-
      0.017,0.128 +/- 0.016,0.134 +/- 0.014,0.163 +/- 0.009; 12 h: 0.149 +/-
      0.013,0.136 +/- 0.018,0.144 +/- 0.013,0.187 +/- 0.010) on corresponding time
      decreased sharply compared with those in control groups (6, 12 h). CONCLUSIONS:
      The human facial hypertrophic scar fibroblasts differentiation in response to
      cyclic stretch was mediated by p38MAPK phosporylation.

PMID- 24438571
TI  - [Surgical treatment of symphyseal fractures and control fixation of mandibular
      width].

PMID- 24438572
TI  - [Bone biomechanics of craniofacial skeleton and bone healing].

PMID- 24438573
TI  - [Assessment and treatment of halitosis].

PMID- 24438574
TI  - [Effect of antibiotics on postoperative inflammatory complications in lower
      impacted third molar surgery].

PMID- 24438575
TI  - [Polyelectrolyte multi-layer films for application in surface modification of
      titanium].

PMID- 24438576
TI  - Surgical lead extraction for total occlusion of the superior vena cava by chronic
      lead infection after mustard procedure.
AB  - We present a case of total occlusion of the superior vena cava (SVC) with
      extensive thrombosis of the adjacent large veins secondary to multiple abandoned
      pacemaker leads with a superimposed chronic lead infection by Corynebacterium
      jeikeium. A surgical lead extraction was performed with an extensive en-bloc
      resection of the SVC together with the right subclavian vein and the right
      innomate vein. No venous reconstruction was required because of an unobstructed
      runoff via a well-developed azygos system.

PMID- 24438577
TI  - Course and treatment of chronic hepatitis E virus infection in lung transplant
      recipients.
AB  - OBJECTIVE: Persistent hepatitis E virus (HEV) infections have been described in
      various transplant cohorts. However, the frequency and the course of HEV
      infection in lung transplant recipients (Lu-Tr) are not well defined. METHODS: We
      retrospectively analyzed serum from 95 Lu-Tr for HEV RNA and anti-HEV
      immunoglobulin-G (IgG) (with the MP assay). Anti-HEV seroprevalence was compared
      to that of 537 healthy individuals. Prospective HEV screening was subsequently
      initiated in Lu-Tr. RESULTS: Elevated liver enzymes were observed in 44/95
      (46.3%) patients. Anti-HEV IgG was present in 5/95 patients (5.3%), revealing a
      slightly higher prevalence compared to controls (2%, 11/537; P = 0.07). Chronic
      HEV infection with detectable viral replication was confirmed by polymerase chain
      reaction in 3 (3.2%) patients, all of whom demonstrated clinical and biochemical
      features of active liver disease (maximum alanine aminotransferase [ALTmax ] 89,
      215, and 270 IU/L, respectively). One patient had died from multi-organ failure
      in combination with liver cirrhosis before HEV diagnosis. Two additional patients
      with chronic hepatitis E were identified during prospective screening (ALTmax 359
      and 318 IU/L). All patients still alive commenced ribavirin therapy for 5 months,
      with dose adjustment (400-600 mg/day) according to renal function and hemoglobin
      level. Sustained resolution of HEV infection occurred in 2 patients. One patient
      is still under treatment, and the fourth died from graft failure considered
      unrelated to ribavirin therapy. CONCLUSION: Chronic hepatitis E should be
      considered in the differential diagnosis of elevated liver enzymes, which are
      commonly seen in Lu-Tr. We observed 1 case of end-stage liver cirrhosis and death
      in an HEV-infected subject, who was not treated with ribavirin. Given this
      potentially devastating consequence, ribavirin therapy of persistent HEV
      infection appears to be acceptably safe and effective in Lu-Tr. However, larger
      prospective studies are warranted.

PMID- 24438579
TI  - Annual research review: Harms experienced by child users of online and mobile
      technologies: the nature, prevalence and management of sexual and aggressive
      risks in the digital age.
AB  - AIMS AND SCOPE: The usage of mobile phones and the internet by young people has
      increased rapidly in the past decade, approaching saturation by middle childhood
      in developed countries. Besides many benefits, online content, contact or conduct
      can be associated with risk of harm; most research has examined whether
      aggressive or sexual harms result from this. We examine the nature and prevalence
      of such risks, and evaluate the evidence regarding the factors that increase or
      protect against harm resulting from such risks, so as to inform the academic and
      practitioner knowledge base. We also identify the conceptual and methodological
      challenges encountered in this relatively new body of research, and highlight the
      pressing research gaps. METHODS: Given the pace of change in the market for
      communication technologies, we review research published since 2008. Following a
      thorough bibliographic search of literature from the key disciplines (psychology,
      sociology, education, media studies and computing sciences), the review
      concentrates on recent, high quality empirical studies, contextualizing these
      within an overview of the field. FINDINGS: Risks of cyberbullying, contact with
      strangers, sexual messaging ('sexting') and pornography generally affect fewer
      than one in five adolescents. Prevalence estimates vary according to definition
      and measurement, but do not appear to be rising substantially with increasing
      access to mobile and online technologies, possibly because these technologies
      pose no additional risk to offline behaviour, or because any risks are offset by
      a commensurate growth in safety awareness and initiatives. While not all online
      risks result in self-reported harm, a range of adverse emotional and psychosocial
      consequences is revealed by longitudinal studies. Useful for identifying which
      children are more vulnerable than others, evidence reveals several risk factors:
      personality factors (sensation-seeking, low self-esteem, psychological
      difficulties), social factors (lack of parental support, peer norms) and digital
      factors (online practices, digital skills, specific online sites). CONCLUSIONS:
      Mobile and online risks are increasingly intertwined with pre-existing (offline)
      risks in children's lives. Research gaps, as well as implications for
      practitioners, are identified. The challenge is now to examine the relations
      among different risks, and to build on the risk and protective factors identified
      to design effective interventions.

PMID- 24438580
TI  - Argon used as dry suit insulation gas for cold-water diving.
AB  - BACKGROUND: Cold-water diving requires good thermal insulation because
      hypothermia is a serious risk. Water conducts heat more efficiently compared to
      air. To stay warm during a dive, the choice of thermal protection should be based
      on physical activity, the temperature of the water, and the duration of exposure.
      A dry suit, a diving suit filled with gas, is the most common diving suit in cold
      water. Air is the traditional dry suit inflation gas, whereas the thermal
      conductivity of argon is approximately 32% lower compared to that of air. This
      study evaluates the benefits of argon, compared to air, as a thermal insulation
      gas for a dry suit during a 1-h cold-water dive by divers of the Royal
      Netherlands Navy. METHODS: Seven male Special Forces divers made (in total) 19
      dives in a diving basin with water at 13 degrees C at a depth of 3 m for 1 h in
      upright position. A rubber dry suit and woollen undergarment were used with
      either argon (n = 13) or air (n = 6) (blinded to the divers) as suit inflation
      gas. Core temperature was measured with a radio pill during the dive. Before,
      halfway, and after the dive, subjective thermal comfort was recorded using a
      thermal comfort score. RESULTS: No diver had to abort the test due to cold. No
      differences in core temperature and thermal comfort score were found between the
      two groups. Core temperature remained unchanged during the dives. Thermal comfort
      score showed a significant decrease in both groups after a 60-min dive compared
      to baseline. CONCLUSIONS: In these tests the combination of the dry suit and
      undergarment was sufficient to maintain core temperature and thermal comfort for
      a dive of 1h in water at 13 degrees C. The use of argon as a suit inflation gas
      had no added value for thermal insulation compared to air for these dives.

PMID- 24438581
TI  - Is there any miscommunication: delaying Pap smear screening in the adolescent
      young adult population?

PMID- 24438583
TI  - Ga0.35In0.65 N0.02As0.08/GaAs bidirectional light-emitting and light-absorbing
      heterojunction operating at 1.3 MUm.
AB  - The Top-Hat hot electron light emission and lasing in semiconductor
      heterostructure (HELLISH)-vertical-cavity semiconductor optical amplifier (THH
      VCSOA) is a bidirectional light-emitting and light-absorbing heterojunction
      device.The device contains 11 Ga0.35In0.65 N0.02As0.08/GaAs MQWs in its intrinsic
      active region which is enclosed between six pairs of AlAs/GaAs top distributed
      Bragg reflectors (DBRs) and 20.5 pairs of AlAs/GaAs bottom DBR mirrors. The THH
      VCSOA is fabricated using a four-contact configuration. The wavelength conversion
      with amplification is achieved by the appropriate biasing of the absorption and
      emission regions within the device. Absorption and emission regions may be
      reversed by changing the polarity of the applied voltage. Emission wavelength is
      about 1,300 nm and a maximum gain at this wavelength is around 5 dB at T = 300 K.

PMID- 24438582
TI  - Promoting sexual and reproductive health among adolescents in southern and
      eastern Africa (PREPARE): project design and conceptual framework.
AB  - BACKGROUND: Young people in sub-Saharan Africa are affected by the HIV pandemic
      to a greater extent than young people elsewhere and effective HIV-preventive
      intervention programmes are urgently needed. The present article presents the
      rationale behind an EU-funded research project (PREPARE) examining effects of
      community-based (school delivered) interventions conducted in four sites in sub
      Saharan Africa. One intervention focuses on changing beliefs and cognitions
      related to sexual practices (Mankweng, Limpopo, South Africa). Another promotes
      improved parent-offspring communication on sexuality (Kampala, Uganda). Two
      further interventions are more comprehensive aiming to promote healthy sexual
      practices. One of these (Western Cape, South Africa) also aims to reduce intimate
      partner violence while the other (Dar es Salaam, Tanzania) utilises school-based
      peer education. METHODS/DESIGN: A modified Intervention Mapping approach is used
      to develop all programmes. Cluster randomised controlled trials of programmes
      delivered to school students aged 12-14 will be conducted in each study site.
      Schools will be randomly allocated (after matching or stratification) to
      intervention and delayed intervention arms. Baseline surveys at each site are
      followed by interventions and then by one (Kampala and Limpopo) or two (Western
      Cape and Dar es Salaam) post-intervention data collections. Questionnaires
      include questions common for all sites and are partly based on a set of social
      cognition models previously applied to the study of HIV-preventive behaviours.
      Data from all sites will be merged in order to compare prevalence and
      associations across sites on core variables. Power is set to .80 or higher and
      significance level to .05 or lower in order to detect intervention effects.
      Intraclass correlations will be estimated from previous surveys carried out at
      each site. DISCUSSION: We expect PREPARE interventions to have an impact on
      hypothesized determinants of risky sexual behaviour and in Western Cape and Dar
      es Salaam to change sexual practices. Results from PREPARE will (i) identify
      modifiable cognitions and social processes related to risky sexual behaviour and
      (ii) identify promising intervention approaches among young adolescents in sub
      Saharan cultures and contexts. TRIAL REGISTRATIONS: Controlled Trials
      ISRCTN56270821 (Cape Town); Controlled Trials ISRCTN10386599 (Limpopo); Clinical
      Trials NCT01772628 (Kampala); Australian New Zealand Clinical Trials Registry
      ACTRN12613000900718 (Dar es Salaam).

PMID- 24438584
TI  - No more 'business as usual' with audit and feedback interventions: towards an
      agenda for a reinvigorated intervention.
AB  - BACKGROUND: Audit and feedback interventions in healthcare have been found to be
      effective, but there has been little progress with respect to understanding their
      mechanisms of action or identifying their key 'active ingredients.' DISCUSSION:
      Given the increasing use of audit and feedback to improve quality of care, it is
      imperative to focus further research on understanding how and when it works best.
      In this paper, we argue that continuing the 'business as usual' approach to
      evaluating two-arm trials of audit and feedback interventions against usual care
      for common problems and settings is unlikely to contribute new generalizable
      findings. Future audit and feedback trials should incorporate evidence- and
      theory-based best practices, and address known gaps in the literature. SUMMARY:
      We offer an agenda for high-priority research topics for implementation
      researchers that focuses on reviewing best practices for designing audit and
      feedback interventions to optimize effectiveness.

PMID- 24438586
TI  - Ghrelin and motilin receptor agonists: time to introduce bias into drug design.
AB  - Ghrelin and motilin receptor agonists increase gastric motility and are
      attractive drug targets. However, 14 years after the receptors were described (18
      24 years since ligands became available) the inactivity of the ghrelin agonist
      TZP-102 in patients with gastroparesis joins the list of unsuccessful motilin
      agonists. Fundamental questions must be asked. Pustovit et al., have now shown
      that the ghrelin agonist ulimorelin evokes prolonged increases in rat colorectal
      propulsion yet responses to other ghrelin agonists fade. Similarly, different
      motilin agonists induce short- or long-lasting effects in a cell-dependent
      manner. Together, these and other data create the hypothesis that the receptors
      can be induced to preferentially signal ('biased agonism') via particular
      pathways to evoke different responses with therapeutic advantages/disadvantages.
      Biased agonism has been demonstrated for ghrelin. Are motilin agonists which
      cause long-lasting facilitation of human stomach cholinergic function (compared
      with motilin) biased agonists (e.g., camicinal, under development for patients
      with gastric hypo-motility)? For ghrelin, additional complications exist because
      the therapeutic aims/mechanisms of action are uncertain, making it difficult to
      select the best (biased) agonist. Will ghrelin agonists be useful treatments of
      nausea and/or as suggested by Pustovit et al., chronic constipation? How does
      ghrelin increase gastric motility? As gastroparesis symptoms poorly correlate
      with delayed gastric emptying (yet gastro-prokinetic drugs can provide relief:
      e.g., low-dose erythromycin), would low doses of ghrelin and motilin agonists
      relieve symptoms simply by restoring neuromuscular rhythm? These questions on
      design and functions need addressing if ghrelin and motilin agonists are to reach
      patients as drugs.

PMID- 24438585
TI  - Glossina palpalis palpalis populations from Equatorial Guinea belong to distinct
      allopatric clades.
AB  - BACKGROUND: Luba is one of the four historical foci of Human African
      Trypanosomiasis (HAT) on Bioko Island, in Equatorial Guinea. Although no human
      cases have been detected since 1995, T. b. gambiense was recently observed in the
      vector Glossina palpalis palpalis. The existence of cryptic species within this
      vector taxon has been previously suggested, although no data are available
      regarding the evolutionary history of tsetse flies populations in Bioko. METHODS:
      A phylogenetic analysis of 60 G. p. palpalis from Luba was performed sequencing
      three mitochondrial (COI, ND2 and 16S) and one nuclear (rDNA-ITS1) DNA markers.
      Phylogeny reconstruction was performed by Distance Based, Maximum Likelihood and
      Bayesian Inference methods. RESULTS: The COI and ND2 mitochondrial genes were
      concatenated and revealed 10 closely related haplotypes with a dominant one found
      in 61.1% of the flies. The sequence homology of the other 9 haplotypes compared
      to the former ranged from 99.6 to 99.9%. Phylogenetic analysis clearly clustered
      all island samples with flies coming from the Western African Clade (WAC), and
      separated from the flies belonging to the Central Africa Clade (CAC), including
      samples from Mbini and Kogo, two foci of mainland Equatorial Guinea. Consistent
      with mitochondrial data, analysis of the microsatellite motif present in the ITS1
      sequence exhibited two closely related genotypes, clearly divergent from the
      genotypes previously identified in Mbini and Kogo. CONCLUSIONS: We report herein
      that tsetse flies populations circulating in Equatorial Guinea are composed of
      two allopatric subspecies, one insular and the other continental. The presence of
      these two G. p. palpalis cryptic taxa in Equatorial Guinea should be taken into
      account to accurately manage vector control strategy, in a country where
      trypanosomiasis transmission is controlled but not definitively eliminated yet.

PMID- 24438587
TI  - On the fiftieth anniversary. Postinfectious irritable bowel syndrome: mechanisms
      related to pathogens.
AB  - BACKGROUND: Gastrointestinal (GI) infections resulting from bacterial, viral, and
      parasitic pathogens predispose to postinfectious irritable bowel syndrome (PI
      IBS) and other functional GI disorders. Existing literature supports the role of
      enterochromaffin cell hyperplasia, serotonin synthesis and reuptake, impaired
      barrier function, altered immune activation, and potentially mast cell activation
      in the pathophysiology of PI-IBS. PURPOSE: The objective of this review was to
      summarize from the literature the characteristics of the pathogens commonly
      implicated in PI-IBS, their acute enteritis phases, and the changes seen in the
      postinfectious phase that may contribute toward development of IBS. A limitation
      of our current understanding is that the postinfectious GI sequelae reported in
      prior studies followed epidemic diarrheal outbreaks often involving more than one
      pathogen, or the studies focused on highly selected, tertiary referral patients.
      Understanding the mechanisms, natural history, and optimized management of
      individuals suffering PI-IBS following the more typical sporadic infection
      requires larger studies of PI-IBS following GI infections encountered in
      community settings. These studies should include genetic, physiological, and
      molecular studies to provide more generalizable information that can ultimately
      be used to diagnose, manage, and potentially prevent the development of PI-IBS.

PMID- 24438589
TI  - Type I interferon signature in the initiation of the immune response in vitiligo.
AB  - Immune-mediated responses are consistently observed in progressing vitiligo at
      the edge of depigmenting patches. Besides the role of the adaptive immune system,
      the profile of the innate immune response is now at the center of the stage. We
      report that plasmacytoid dendritic cells (pDC), which are the major interferon
      (IFN)-alpha-producing cells, are part of the infiltrate of progressive vitiligo
      with local production of MxA (a protein induced by IFNalpha). MxA was associated
      with expression of the type I IFN-inducible ligand CXCL9 and correlated with the
      recruitment of CXCR3(+) immune cells. Interestingly, strong MxA expression was
      observed in perilesional skin in close apposition to remaining melanocytes,
      surrounded by a prominent T-cell infiltrate. In contrast, MxA was not detectable
      in lesional skin, suggesting that IFN-alpha production is an early event in the
      progression of the disease. Our data highlight a new innate immune pathway
      leading to progression of vitiligo.

PMID- 24438590
TI  - Core content for wilderness medicine fellowship training of emergency medicine
      graduates.
AB  - Wilderness medicine is the practice of resource-limited medicine under austere
      conditions. In 2003, the first wilderness medicine fellowship was established,
      and as of March 2013, a total of 12 wilderness medicine fellowships exist. In
      2009 the American College of Emergency Physicians Wilderness Medicine Section
      created a Fellowship Subcommittee and Taskforce to bring together fellowship
      directors, associate directors, and other interested stakeholders to research and
      develop a standardized curriculum and core content for emergency medicine (EM)
      based wilderness medicine fellowships. This paper describes the process and
      results of what became a 4-year project to articulate a standardized curriculum
      for wilderness medicine fellowships. The final product specifies the minimum core
      content that should be covered during a 1-year wilderness medicine fellowship. It
      also describes the structure, length, site, and program requirements for a
      wilderness medicine fellowship. 

PMID- 24438588
TI  - Genome sequence of Anopheles sinensis provides insight into genetics basis of
      mosquito competence for malaria parasites.
AB  - BACKGROUND: Anopheles sinensis is an important mosquito vector of Plasmodium
      vivax, which is the most frequent and widely distributed cause of recurring
      malaria throughout Asia, and particularly in China, Korea, and Japan. RESULTS: We
      performed 454 next-generation sequencing and obtained a draft sequence of A.
      sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of
      this genome sequence, we observed expansion and contraction of several immune
      related gene families in anopheline relative to culicine mosquito species. These
      differences suggest that species-specific immune responses to Plasmodium invasion
      underpin the biological differences in susceptibility to Plasmodium infection
      that characterize these two mosquito subfamilies. CONCLUSIONS: The A. sinensis
      genome produced in this study, provides an important resource for analyzing the
      genetic basis of susceptibility and resistance of mosquitoes to Plasmodium
      parasites research which will ultimately facilitate the design of urgently needed
      interventions against this debilitating mosquito-borne disease.

PMID- 24438591
TI  - Differences between lutropin-mediated and choriogonadotropin-mediated receptor
      activation.
AB  - The human lutropin/choriogonadotropin receptor (hLHR) for the gonadotropic
      hormones human luteinizing hormone (hLH; lutropin) and human choriogonadotropin
      (hCG) is crucial for normal sexual development and fertility. We aimed to unravel
      differences between the two hLHR hormones in molecular activation mechanisms at
      hLHR. We utilized a specific hLHR variant that lacks exon 10 (hLHR-delExon10),
      which maintains full cAMP signaling by hCG, but decreases hLH-induced receptor
      signaling, resulting in a pathogenic phenotype. Exon 10 encodes 27 amino acids
      within the hinge region, which is an extracellular segment that is important for
      signaling and hormone interaction. Initially, we assumed that the lack of exon 10
      might disturb intermolecular trans-activation of hLH, a mechanism that has been
      reported for hCG at hLHR. Coexpression of signaling-deficient hLHR and binding
      deficient hLHR can be used to examine the mechanisms of receptor signaling, in
      particular intermolecular cooperation and intramolecular cis-activation.
      Therefore, hLHR-delExon10 was combined with the hLHR Lys605->Glu mutant, in which
      signaling is abolished, and the hLHR mutant Cys131->Arg, in which binding is
      deficient. We found that hCG signaling was partially rescued, indicating trans
      activation. However, the hLH signal could not be restored via forced trans
      activation with any construct. Fluorescence cross-correlation spectroscopy
      detected oligomerization in all combinations, indicating that these functional
      differences cannot be explained by monomerization of hLHR-delExon10. Thus, our
      data demonstrate not only that the different behavior of hLH at hLHR-delExon10 is
      unlikely to be related to modified intermolecular receptor activation, but also
      that hLH may exclusively stimulate the targeted hLHR by cis-activation, whereas
      hCG is also capable of inducing trans-activation.

PMID- 24438593
TI  - Collective wisdom and multidisciplinary tumor boards.

PMID- 24438592
TI  - Improving accountability through alignment: the role of academic health science
      centres and networks in England.
AB  - BACKGROUND: As in many countries around the world, there are high expectations on
      academic health science centres and networks in England to provide high-quality
      care, innovative research, and world-class education, while also supporting
      wealth creation and economic growth. Meeting these expectations increasingly
      depends on partnership working between university medical schools and teaching
      hospitals, as well as other healthcare providers. However, academic-clinical
      relationships in England are still characterised by the "unlinked partners"
      model, whereby universities and their partner teaching hospitals are neither
      fiscally nor structurally linked, creating bifurcating accountabilities to
      various government and public agencies. DISCUSSION: This article focuses on
      accountability relationships in universities and teaching hospitals, as well as
      other healthcare providers that form core constituent parts of academic health
      science centres and networks. The authors analyse accountability for the
      tripartite mission of patient care, research, and education, using a four-fold
      typology of accountability relationships, which distinguishes between
      hierarchical (bureaucratic) accountability, legal accountability, professional
      accountability, and political accountability. Examples from North West London
      suggest that a number of mechanisms can be used to improve accountability for the
      tripartite mission through alignment, but that the simple creation of academic
      health science centres and networks is probably not sufficient. SUMMARY: At the
      heart of the challenge for academic health science centres and networks is the
      separation of accountabilities for patient care, research, and education in
      different government departments. Given that a fundamental top-down system
      redesign is now extremely unlikely, local academic and clinical leaders face the
      challenge of aligning their institutions as a matter of priority in order to
      improve accountability for the tripartite mission from the bottom up. It remains
      to be seen which alignment mechanisms are most effective, and whether they are
      strong enough to counter the separation of accountabilities for the tripartite
      mission at the national level, the on-going structural fragmentation of the
      health system in England, and the unprecedented financial challenges that it
      faces. Future research should focus on determining the comparative effectiveness
      of different alignment mechanisms, developing standardised metrics and key
      performance indicators, evaluating and assessing academic health science centres
      and networks, and empirically addressing leadership issues.

PMID- 24438594
TI  - Transoral open reduction of mandibular condyle fractures in children: is there
      proven benefit?

PMID- 24438595
TI  - Proceedings from the 2013 American Association of Oral and Maxillofacial Surgeons
      Research Summit.
AB  - The American Association of Oral and Maxillofacial Surgeons, the Oral and
      Maxillofacial Surgery Foundation, and the International Association of Oral and
      Maxillofacial Surgeons sponsored the fifth research summit, which convened on May
      2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to
      facilitate the discussion and collaboration of oral and maxillofacial surgeons
      with clinical and basic science researchers in fields affecting the specialty.
      The goal is to advance the field of oral and maxillofacial surgery through
      exposure and education in topics that ultimately benefit the oral and
      maxillofacial surgical patient. This edition of the research summit included the
      topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws
      (ARONJ). Most importantly, this research summit saw the development of research
      interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and
      reconstructive surgery, obstructive sleep apnea and orthognathic surgery,
      temporomandibular joint surgery, and trauma. These RIGs developed specific
      research goals with a plan to continue working on potential projects at the AAOMS
      Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann
      Arbor. The summit program was developed by the AAOMS Committee on Research
      Planning and Technology Assessment. The charge of the committee is to encourage
      and promote research within the specialty and to encourage interdisciplinary
      collaboration. The research summit serves as a platform for oral and
      maxillofacial surgeons to lead the goal of advancement of research relevant to
      the specialty. This article provides an overview of the presentations that were
      made in the sessions on robotic surgery and ARONJ. The research summit keynote
      address and two additional presentations on patient registries are summarized and
      updates from the RIGs that were formed at the 2013 research summit are
      highlighted. 

PMID- 24438596
TI  - Single-dose intra-alveolar chlorhexidine gel application, easier surgeries, and
      younger ages are associated with reduced dry socket risk.
AB  - PURPOSE: Although dry socket (DS) is commonly investigated, many of its risk
      factors remain highly controversial. In addition, few studies are available to
      show the preventive effect of chlorhexidine gel on DS. Moreover, multivariable
      analyses of DS risk factors are scarce, and their interactions have not been
      assessed previously. Therefore, the simultaneous effect of chlorhexidine gel and
      4 DS risk factors and their interactions were analyzed within a multivariable
      framework. MATERIALS AND METHODS: Using a split-mouth randomized clinical trial
      design, the investigators enrolled a cohort of patients requiring extraction of 2
      mandibular third molars. The primary predictor variable was extraction socket
      treatment status, classified as experimental or standard. Experimental treatment
      was the insertion of chlorhexidine gel (0.2%) into the extraction socket. Each
      patient had 1 third molar randomly selected as the treatment site. The
      contralateral third molar served as the control socket and was treated in the
      usual manner. The primary outcome variable was DS status, present or absent,
      assessed on postoperative day 3. Other study variables were categorized as
      demographic, smoking, and surgical difficulty according to the Pederson scale.
      Appropriate bivariate and multiple logistic regression statistics were used to
      measure the association between risk for DS and chlorhexidine gel use, age,
      gender, smoking, and surgical difficulty and their interactions (alpha = 0.05).
      RESULTS: The sample consisted of 90 bilateral extraction sockets in 45 patients
      (24 men; 21 smokers; mean age, 21.1 +/- 2.7 yr). Regression analysis showed that
      when other factors and their interactions were controlled for, chlorhexidine gel
      application lowered the risk of DS (odds ratio [OR] = 0.05; P = .004). Increasing
      age (OR = 2.9; P = .030) was associated with an increased risk for DS. A similar
      association existed between increased difficulty level of extraction and DS risk
      (OR = 3.8; P = .051). The effect of gender was marginally significant (P = .091),
      whereas smoking did not have a significant influence (P = .4). CONCLUSIONS: Intra
      alveolar application of chlorhexidine gel and practicing less traumatic surgeries
      are advocated, particularly in older patients. Smoking seems unlikely to affect
      DS frequency. The role of gender is inconclusive.

PMID- 24438597
TI  - Vertical ridge augmentation using the modified shell technique--a case report.
AB  - PURPOSE: Vertical defects of the alveolar crest limit implant placements.
      Accordingly, hard tissue grafting is essential in a separate procedure before
      implant placement; however, the outcome of vertical bone augmentation is
      unpredictable. MATERIALS AND METHODS: This case report describes a new approach
      to vertical hard tissue grafting using the modified autogenous shell technique.
      With the help of a bone mill, the bone graft was trimmed to a shell with a
      thickness of less than 1 mm and seeded to rebuild the vertical dimension of the
      alveolar ridge. The shell was fixated with titanium microscrews, and the vertical
      distance between the shell and the residual bone was filled with autogenous
      particulate bone. RESULTS: Wound healing was uneventful. Corticalization was
      observed across the bone chips, and there was only a small vertical resorption of
      the shell. Two implants could be inserted above the alveolar nerve into the
      augmented bone. CONCLUSION: The modified shell technique showed promising results
      for the reconstruction of vertical bone defects. This technique could decrease
      the need for bone grafts taken from the iliac crest.

PMID- 24438598
TI  - Age-based treatment of aggressive fibromatosis in the head and neck region.
AB  - PURPOSE: To review our experience regarding the difference in management and
      treatment outcomes of aggressive fibromatosis of the head and neck region in
      children and adults, emphasizing, in particular, the role of conservative surgery
      in comprehensive treatment strategies. PATIENTS AND METHODS: A retrospective
      analysis of patients with aggressive fibromatosis was performed during a 5-year
      period (2008 to 2012). Nine patients were enrolled in the present study,
      including 5 children (age, <18 years) and 4 adults (age, >18 years). All patients
      underwent surgical intervention and were treated by surgical resection with
      different surgical margins. Adjuvant low-dose chemotherapy and radiotherapy were
      given to pediatric and adult patients, respectively, with macroscopically or
      microscopically positive surgical margins. RESULTS: All 5 pediatric patients (3
      females and 2 males) received low-dose chemotherapy after conservative surgical
      resection (in 4 patients, microscopically incomplete resection; and in 1 patient,
      macroscopic residual tumor). Of the 4 adults (3 females and 1 male), 2 underwent
      complete surgical resection and 2 underwent surgery and postoperative
      radiotherapy (1 patient had microscopically suspected residual tumor and 1 had
      macroscopic residual tumor). The patients were followed up for a period of 7 to
      51 months. Two pediatric patients and one adult patient had disease progression
      after resection and became stable after continued adjuvant therapy. None of the
      patients had functional or cosmetic defects. All patients had good long-term
      outcomes, with no disease progression. CONCLUSIONS: For the treatment of
      aggressive fibromatosis, conservative resection with preservation of form and
      function should be given greater priority in all age groups. Also, postoperative
      adjuvant therapy is vital for patients with gross or microscopic residual tumor
      to obtain progression-free survival.

PMID- 24438599
TI  - Efficacy and safety of dexmedetomidine versus propofol for the sedation of tube
      retention after oral maxillofacial surgery.
AB  - PURPOSE: To compare the safety and efficacy of sedation induced by
      dexmedetomidine and propofol after oral and maxillofacial surgery. MATERIALS AND
      METHODS: In this trial, 66 patients 18 to 50 years old received oral and
      maxillofacial surgery and required postoperative nasal endotracheal intubation
      under overnight sedation with dexmedetomidine or propofol. The dexmedetomidine
      group (group D) received dexmedetomidine 1.0 MUg/kg intravenously for 10 minutes
      after entering the recovery room. The dose was maintained by giving an
      intravenous injection of dexmedetomidine 0.4 MUg/kg. The injection rate could be
      modulated from 0.2 to 0.7 MUg/kg/hour in the intensive care unit (ICU). If the
      Ramsay score was lower than 2 and involuntary limb movement occurred, other
      sedatives were used. The propofol group (group P) was given propofol 0.1 mg/kg
      intravenously for 10 minutes after entering the recovery room and then maintained
      with intravenous injections of propofol 1 to 2 mg/kg/hour in the recovery room
      and ICU. RESULTS: The oxygen desaturation of group P was higher than that of
      group D (at the first sedation time of 30 minutes), but the mean blood pressure
      of group P was significantly lower than that of group D at the 10-minute time
      point. The Ramsay score was higher in group D after the first 3 hours of sedation
      than in group P (P < .05). CONCLUSION: Dexmedetomidine showed similar safety and
      efficacy as propofol and could be used for tube-retaining sedation after oral and
      maxillofacial surgery.

PMID- 24438600
TI  - Guided bone regeneration using chitosan-collagen membranes in dog dehiscence-type
      defect model.
AB  - PURPOSE: The purpose of the present study was to compare a newly developed
      chitosan-collagen membrane (CCM) with a standard collagen membrane (SCM)
      regarding their effects on guided bone regeneration. MATERIALS AND METHODS: The
      right mandibular premolars and first molar were extracted from 12 beagle dogs.
      Four months later, acute buccal dehiscence-type defects (4 * 3 mm in height and
      width) were surgically created after implant site preparation. The defects were
      randomly assigned to 4 different groups: CCM-1 (weight ratio of chitosan to
      collagen of 40:1), CCM-2 (weight ratio of chitosan to collagen of 20:1), SCM, and
      vehicle control. The dogs were sacrificed after 4, 8, and 12 weeks of healing for
      radiographic examination, histologic observation, and histometric analysis.
      RESULTS: The membrane-treated sites showed more bone formation than the control
      sites, although no statistically significant differences were found between the
      membrane-treated sites and the control sites for new bone-to-implant contact and
      new bone-filled area at any point. At 8 weeks, the new bone height for the
      membrane-treated sites was significantly greater statistically than that of the
      untreated group (P < .05). At 12 weeks, the CCM-1 group showed significantly
      greater new bone height (1.91 +/- 0.25 mm) than the untreated group (1.20 +/-
      0.34 mm; P < .05). However, the CCMs did not show any statistically significant
      differences compared with the SCMs for any assessed parameter. CONCLUSIONS: The
      results of the present study have shown that the developed CCMs can enhance bone
      regeneration and could be a candidate for use in guided bone regeneration.

PMID- 24438601
TI  - Amoxicillin administrations and its influence on bone repair around
      osseointegrated implants.
AB  - PURPOSE: The objective of this study was to evaluate the influence of 4 different
      amoxicillin administration protocols on osseointegration of dental implants.
      MATERIALS AND METHODS: Thirty-five Wistar rats received an implant in the right
      tibia and were divided into 5 groups (n = 7): the control group (G1), a group
      that received a single dose of amoxicillin suspension (40 mg/kg) hour before
      surgery (G2), a group that received amoxicillin suspension 1 hour before surgery
      and a 10-mg/kg dose every 12 hours for 3 days (G3), a group that received
      amoxicillin suspension 1 hour before surgery and a 10-mg/kg dose every 12 hours
      for 5 days (G4), and a group that received amoxicillin suspension 1 hour before
      surgery and a 10-mg/kg dose every 12 hours for 7 days (G5). The animals were
      sacrificed by anesthesia overdose 28 days after implant placement. The samples
      were retrieved for bone-to-implant contact (BIC) and bone area fraction occupancy
      (BAFO) analyses. RESULTS: BIC analysis indicated 3 different statistical groups:
      G1 plus G2, G3, and G4 plus G5. There was no statistical difference between G1
      and G2 or between G4 and G5. G3 presented lower values, with statistical
      difference for G1 plus G2 and G4 plus G5. Also, a statistical difference was
      found between G1 plus G2 and G4 plus G5. For BAFO evaluation, no statistical
      difference was found for the experimental groups. CONCLUSION: The results of this
      study suggest that prolonged use of amoxicillin might have a negative effect on
      bone formation around implants.

PMID- 24438602
TI  - Buccal fat pad lifting: an alternative open technique for malar augmentation.
AB  - PURPOSE: The purpose of the study was to introduce a novel technique for malar
      augmentation using buccal fat pad pedicle flaps and to evaluate the long-term
      results and complications of the technique. MATERIALS AND METHODS: The
      investigators designed and conducted a prospective clinical trial. Patients
      underwent unilateral malar augmentation surgery using buccal fat pad pedicle
      flaps from June 2011 through June 2012. Patients underwent surgery for esthetic
      reasons or for trauma with severely comminuted or old zygomaticomaxillary complex
      fractures that could not be reduced precisely. The primary predictor variable was
      the buccal fat pad pedicle flap technique. The primary outcome variables included
      the amount of augmentation and resorption (which was estimated by comparing pre-
      with postsurgical photographic views), pain, edema, bruising, and nerve and
      parotid duct injuries. RESULTS: Thirteen patients (8 men and 5 women) underwent
      malar augmentation in the cheekbone area using the buccal fat pad pedicle flap
      technique. One year after surgery, the average amount of resorption was 0.376 mm.
      Other major complications, such as prolonged bruising, massive hematoma, intense
      pain, asymmetry, and parotid duct injury, were not observed. CONCLUSION: These
      results indicate that this new open-access technique should be considered an
      alternative method for the management of mild to moderate malar depression in
      patients undergoing esthetic and post-trauma surgery.

PMID- 24438603
TI  - Cannabinoid modulation of predator fear: involvement of the dorsolateral
      periaqueductal gray.
AB  - The present study investigated the effects of systemic or intra-dorsolateral
      periaqueductal gray (dlPAG) administration of CB1 agonists on behavioural changes
      induced in rats by predator (a live cat) exposure, a model of panic responses.
      Since nitric oxide (NO) and cannabinoid neurotransmission are proposed to
      interact in the dlPAG to modulate defensive responses, we also investigated if NO
      is involved in the biphasic effects of anandamide (AEA) injected into the dlPAG.
      The results showed that systemic administration of WIN55,212-2 or intra-dlPAG AEA
      attenuated the defensive behaviours caused by cat exposure. Both compounds
      produced biphasic curves. The cannabinoid receptor type 1 (CB1) antagonist AM251
      prevented the panicolytic effect of AEA whereas a neuronal NOS inhibitor turned
      the ineffective high dose of AEA into an effective one. These results suggest
      that modulation of the cannabinoid system could be a target in the treatment of
      panic disorders. However, the biphasic effects of these compounds could limit
      their therapeutic potential. 

PMID- 24438604
TI  - Self-monitoring of blood glucose in type 2 diabetic patients in China: current
      status and influential factors.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) by individuals with type 2
      diabetes (T2D) is crucial for long-term health, yet numerous cultural, economic
      and health factors can reduce SMBG. Most studies on SMBG adherence have come out
      of the US and Europe, and their relevance to Asia is unclear. The aims of the
      present study were to assess the current state of SMBG in China and analyze
      demographic and diabetes-related characteristics that may influence it. METHODS:
      In this multi-center, cross-sectional study, 5 953 individuals with T2D from 50
      medical centers in 29 provinces across China filled out a standardized
      questionnaire that requested information on demographic characteristics,
      education level, occupation, income, lifestyle risk factors, duration of
      diabetes, chronic complications, and frequency of SMBG. Respondents were also
      asked whether their glycosylated hemoglobin (HbA1c) had been checked in the past
      6 months. The most recent values for fasting plasma glucose, 2-hour postprandial
      blood glucose and HbA1c were recovered from medical records. RESULTS: Only 1 130
      respondents (18.98%) performed SMBG with the recommended frequency, while 4 823
      (81.02%) did not. In fact, nearly 2 105 (35.36%) reported never performing SMBG.
      In the subset of 3 661 individuals on insulin therapy, only 266 (7.27%) performed
      SMBG at least once a day, while 1 210 (33.05%) never performed it. In contrast,
      895 of 2 292 individuals (39.05%) on diet/exercise therapy or oral hypoglycemic
      therapy never performed it. Multivariate Logistic regression identified several
      factors associated with SMBG adherence: female gender, higher education level,
      higher income, longer T2D duration and education about SMBG. CONCLUSIONS: SMBG
      adherence in our Chinese population with T2D was less frequent than that in
      developed countries. Several factors influence SMBG adherence: gender, education
      level, income, T2D duration, therapy regimen and exposure to education about
      SMBG.

PMID- 24438605
TI  - Biphasic insulin aspart 30 improved glycemic control in Chinese patients with
      type 2 diabetes poorly controlled on oral glucose-lowering drugs: a subgroup
      analysis of the A1chieve study.
AB  - BACKGROUND: The effectiveness and safety of initiating biphasic insulin aspart 30
      in patients who were poorly controlled on oral glucose-lowering drugs were
      studied in randomized controlled trials, while results from clinical practice
      remain limited. This subgroup analysis was to provide such findings from a large
      scale non-interventional study. METHODS: A1chieve was a multinational,
      prospective, open-label, non-interventional, 24-week study in patients with type
      2 diabetes initiating insulin analogues in 28 countries across Asia, Africa,
      Europe, and Latin America. After physician had taken the decision to use this
      insulin, any patient with type 2 diabetes who was not treated with or who had
      started the study insulin within 4 weeks before inclusion was eligible. Patients
      were treated with study insulin alone or in combination with oral glucose
      lowering drugs. Data on adverse drug reactions, hypoglycemia and glycemic control
      were collected at baseline, week 12 and 24. This is a report of a Chinese
      subgroup analysis from the A1chieve study. RESULTS: Totally, 4 100 patients
      constituted this subgroup. No serious adverse drug reactions were reported. Rates
      of total, major, nocturnal hypoglycemic events (events/patient per year) were
      1.47, 0.10, 0.31 at baseline and 1.35, 0.00, 0.22 at week 24, respectively.
      Glycemic control was improved as measured by hemoglobin A1c (mean 9.3% to 7.0%,
      reduction -2.3%), fasting plasma glucose (mean 10.2 to 6.8 mmol/L, reduction -3.5
      mmol/L) and postprandial plasma glucose (mean 14.4 to 8.8 mmol/L, reduction -5.6
      mmol/L), all P < 0.001. Change in mean body weight was +0.3 kg (P < 0.001).
      CONCLUSION: In this subgroup analysis of the A1chieve study, biphasic insulin
      aspart 30 improved glycemic control with low risk of hypoglycemia.

PMID- 24438606
TI  - Mitochondrial apoptosis of lymphocyte is induced in type 2 diabetes.
AB  - BACKGROUND: Lymphocyte function and homeostasis is associated with immune defence
      to infection. Apoptosis of lymphocytes might be a considerably important
      component which has an impact on immunity to infections in people with
      hyperglycemia. The aim of this study was to explore the mitochondrial apoptosis
      pathway of lymphocyte in diabetic patients. METHODS: Sixty patients with type 2
      diabetes mellitus and fifty healthy volunteers were included in this study.
      Annexin V and propidiumiodide (PI) were joined in the isolated lymphocytes and
      the rate of lymphocyte apoptosis was calculated with flow cytometry. Observation
      of the lymphocytes was done using transmission electron microscopy; mitochondria
      had been extracted and then mitochondrial membrane potential (MMP) was detected
      to assess mitochondrial function; the mRNA level of Bcl-2, cytochrome c (Cyt-C),
      caspase-9 and caspase-3 were analyzed by real-time reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Apoptosis rate of lymphocyte was
      significantly higher in diabetic group than that in normal control group (P <
      0.05). Transmission electron microscopy showed lymphocyte shrinkage and breakage,
      chromatin condensation and less mitochondria; a fall in MMP levels was also
      evident; Bcl-2 concentration was reduced and the expressions of caspase-9,
      caspase-3 and Cyt-C were elevated (P < 0.05) in diabetic patients. CONCLUSIONS:
      The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic
      patients than that in normal population. Mitochondrial apoptosis pathway may play
      a very important role in decreasing function of lymphocyte in diabetes.

PMID- 24438607
TI  - Effect of simvastatin on the expression of farnesoid X receptor in diabetic
      animal models of altered glucose homeostasis.
AB  - BACKGROUND: Statin therapy has affected glucose homoeostasis of type 2 diabetes
      patients, which could be related with bile acids metabolism. Whether bile acid
      metabolism and the expression of farnesoid X receptor (FXR), liver X receptor
      alpha (LXR-alpha) and sterol regulatory element-binding protein (Srebp)-1c is
      regulated by hyperglycemia, or whether simvastatin therapy led to higher glucose
      is related with down-regulated expression of FXR in diabetic rats remained
      unclear. METHODS: Forty male Wistar rats were randomly divided into four groups:
      normal control rats, insulin resistance rats, diabetic model rats, and the late
      simvastatin induced diabetic rats. Normal control rats were fed with standard
      diet, others were fed with high-fat diet. Diabetic model rats were induced by a
      single intraperitoneal injection of streptozotocin (STZ). The late simvastatin
      induced diabetic rats started simvastatin administration after STZ induced
      diabetic model rats. Characteristics of fasting blood glucose (FPG), lipid files
      and total bile acids (TBAs) were measured and the oral glucose tolerance test
      (OGTT) was performed after overnight fasting at the eighth weekend. RNA and
      protein levels of FXR, LXR-alpha and Srebp-1c were tested by Western blotting and
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The insulin
      resistance rats showed higher glucose, lipid files and lower expression of FXR
      compared with normal control rats (P > 0.05). The diabetic model rats showed
      significantly higher glucose, lipid files, TBA and lower expression of FXR
      compared with insulin resistance rats (P < 0.05). The late simvastatin induced
      diabetic rats displayed higher glucose and TBA and lower expression of FXR
      compared with diabetic model rats (P < 0.05). CONCLUSIONS: Changes in bile acid
      homeostasis, including the alterations of bile acid levels and bile acid
      receptors, are either a cause or a consequence of the metabolic disturbances
      observed during diabetic models. Statin therapy induced hyperglycemia may be
      related with FXR, SHP, LXR-alpha and Srebp-1 pathways.

PMID- 24438608
TI  - Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, ameliorates hepatic
      fibrosis in rats with type 2 diabetes.
AB  - BACKGROUND: Hyperglycemia may accelerate liver fibrosis. Currently, there is no
      effective treatment for liver fibrosis induced by type 2 diabetes. The study aim
      was to investigate whether RhoA/Rho kinase (ROCK) pathway is involved in liver
      fibrosis in the rats with type 2 diabetes and define the protective effects of
      fasudil on livers. METHODS: A rat model of type 2 diabetes was established by
      high fat diet combined with streptozotocin (30 mg/kg, intraperitoneal injection).
      Animals were randomly assigned to 3 groups: control rats, untreated diabetic rats
      that received vehicle and fasudil-treated diabetic rats that received ROCK
      inhibitor fasudil hydrochloride hydrate (10 mg/kg per day, intraperitoneal
      injection, for 14 weeks). The morphological features of liver were observed by HE
      staining. Accumulation of collagen in livers was determined by Masson staining
      and the measurement of hydroxyproline. The mRNA expression of transforming growth
      factor-beta1 (TGFbeta1), connective tissue growth factor (CTGF), type-I, and type
      III procollagen was assessed with real-time polymerase chain reaction. The
      phosphorylation of myosin phosphatase target subunit-1 (MYPT1) and the protein
      levels of TGFbeta1 and alpha-smooth muscle actin (a-SMA) were evaluated by
      Western blotting. RESULTS: Compared with control rats, untreated diabetic rats
      showed higher values of collagen and hydroxyproline in livers (P < 0.01), the
      phosphorylation of MYPT1 and the protein levels of TGFbeta1 and alpha-SMA were
      increased (P < 0.01), and the mRNA expression of TGFbeta1, CTGF, type-I, and type
      III procollagen was upregulated (P < 0.01); compared with untreated diabetic
      rats, treatment with fasudil signifcantly reduced values of collagen and
      hydroxyproline (P < 0.01), and decreased the phosphorylation of MYPT1 and the
      levels of TGFbeta1 and alpha-SMA (P < 0.01), concomitant with the downregulation
      of TGFbeta1/CTGF, type-I, and type-III procollagen mRNA expression (P < 0.01).
      CONCLUSIONS: Fasudil ameliorates liver fibrosis in rats with type 2 diabetes at
      least partly by inhibiting TGFbeta1/CTGF pathway and alpha-SMA expression.
      Inhibition of RhoA/ROCK may be a novel therapeutic target for liver fibrosis in
      diabetic non-alcoholic steatohepatitis.

PMID- 24438609
TI  - Robotic stereotactic irradiation and reirradiation for spinal metastases: safety
      and efficacy assessment.
AB  - BACKGROUND: Spine is the most common site of bone metastases in patients with
      cancer. Conventional external beam radiotherapy lacks precision to allow delivery
      of large fraction radiation but simultaneously limit the dose to spinal cord. The
      purpose of this study was to evaluate the safety and efficacy of CyberKnife((r))
      radiation therapy for spinal metastases. METHODS: Seventy-three lesions in 62
      patients treated with CyberKnife radiotherapy from September 2006 to June 2010
      for spinal metastases were retrospectively reviewed. Thirteen tumors in 12
      patients had received prior radiation. Patients were followed clinically and
      radiographically for at least 12 months or until death. In all patients, the
      spinal cord and thecal sac were contoured for dose-volume constraints, and
      maximum doses to 0.1, 0.5, 1, 2, and 5-ml volumes were analyzed. RESULTS: Using
      the CyberKnife System, 20-48 Gy in one to five fractions for unirradiated
      patients, and 21-38 Gy in one to five fractions for the previously irradiatied
      patients, were delivered. Median 2-Gy normalized Biological Equvalent Dose (nBED)
      of unirradiated targets and irradiated targets were 49.6 Gy10/2 (range, 31.25
      74.8 Gy10/2) and 46.9 Gy10/2 (range, 29.8-66 Gy10/2), respectively. With a median
      follow-up of 9.4 months (range, 2.5-45 months), twenty-nine patients (46.7%) were
      alive, whereas the others died of progressive disease. Fifty-six patients (93.3%)
      reported complete or partial reduction of pain after CyberKnife radiotherapy at
      one-month follow-up, 17 patients (28.3%) reported some degree of pain relief
      after first fraction of the treatment course. Two patients experienced local
      recurrence at fifth and ninth months post-radiotherapy. Median maximum nBED for
      spinal cord and thecal sac of naive targets were 68.6 Gy2/2 (range, 8.3-154.5
      Gy2/2) and 83.5 Gy2/2 (range, 10.5-180.5 Gy2/2), respectively. Median maximum
      nBED for spinal cord and thecal sac for the re-irradiated targets were 58.6 Gy2/2
      (range, 17.7-140 Gy2/2) and 70.5 Gy2/2 (range, 21.7-141.3 Gy2/2), respectively.
      No patient developed radiation related myelopathy during the follow-up period.
      CONCLUSION: Cyberknife radiotherapy is clinically effective and safe for spinal
      metastases, even in previously irradiated patients.

PMID- 24438610
TI  - Perioperative factors related to prognosis of regular hepatectomy in comparison
      with irregular hepatectomy.
AB  - BACKGROUND: The aim of this research was to analyze the perioperative factors of
      regular hepatectomy and irregular hepatectomy. The superiority of the clinical
      application of the two methods was compared in the perioperative period. METHODS:
      From 1986 to 2011, 1798 patients underwent consecutive liver resections with
      regular hepatectomy and irregular hepatectomy at the Air Force General Hospital
      of People's Liberation Army and the General Hospital of Chinese People's
      Liberation Army. Their medical documentation was investigated retrospectively.
      RESULTS: In patients on whom regular hepatectomy and irregular hepatectomy were
      performed, there was no significant difference in perioperative blood loss,
      complications, in-hospital mortality, hospital stay, and so on. But in regular
      hepatectomy, operating time was an independent risk factor (P < 0.001, OR =
      1.004). CONCLUSIONS: There was no significant difference between the
      perioperative risk of regular hepatectomy and that of irregular hepatectomy.

PMID- 24438611
TI  - Comparison of immunohistochemistry with fluorescence in situ hybridization in
      determining the human epidermal growth factor receptor 2 status of breast cancer
      specimens: a multicenter study of 3,149 Chinese patients.
AB  - BACKGROUND: Accurate detection of human epidermal growth factor receptor 2 (HER2)
      expression and gene amplification is crucial for the application of HER2-specific
      therapy and for evaluating the response of patients with breast cancer. A uniform
      and standard procedure of immunohistochemistry (IHC) and fluorescence in situ
      hybridization (FISH) needs to be established for evaluating the HER2 status in
      breast cancer tissues for the treatment of patients with real HER2-positive
      tumors. The present multicenter study was aimed to examine the HER2 status in
      breast cancer specimens from Chinese patients using both IHC and FISH methods.
      METHODS: A multicenter study was performed on the HER2 status in 3 149 breast
      cancer specimens from different ethnic populations and areas in China by IHC and
      FISH assays. The potential association of HER2 status with demographic and
      clinical characteristics was analyzed. RESULTS: The positive rates for HER2 over
      expression and HER2 amplification were 23.3% and 27.5% in this study,
      respectively. The concordance between IHC and FISH was 71.2% (kappa = 0.494, P <
      0.001). Furthermore, 72.9% of specimens with IHC 2+ were negative to FISH. The
      discordance rates among laboratories were from 5% to 28% for IHC and 1% to 16%
      for FISH. HER2 amplification was associated significantly with advanced tumor
      stage (III or IV, P = 0.002), large tumor size (>5 cm, P = 0.002), moderate and
      poor histological grades (P < 0.0001), post-menopause (P < 0.0001), ER-PR- (P =
      0.002), and having >= 4 lymph nodes affected (P < 0.0001) in this population. The
      positive rates of HER2 amplification in specimens from Man and Hui Chinese were
      significantly higher than that in other Chinese populations. There are slightly
      higher positive rates of HER2 expression and amplification in Chinese patients
      with breast cancer. CONCLUSION: These findings may provide new insights into
      understanding the epidemiological features of HER2 expression and amplification,
      and may be valuable for clinical practice.

PMID- 24438612
TI  - Prediction of H7N9 epidemic in China.
AB  - BACKGROUND: In March 2013, human cases of infection with a novel A (H7N9)
      influenza virus emerged in China. The epidemic spread quickly and as of 6 May
      2013, there were 129 confirmed cases. The purpose of this study was to analyze
      the epidemiology of the confirmed cases, determine the impacts of bird migration
      and temperature changes on the H7N9 epidemic, predict the future trends of the
      epidemic, explore the response patterns of the government and propose preventive
      suggestions. METHODS: The geographic, temporal and population distribution of all
      cases reported up to 6 May 2013 were described from available records. Risk
      assessment standard was established by analysing the temperature and relative
      humidity records during the period of extensive outbreak in three epidemic
      regions in eastern China, including Shanghai, Zhejiang and Jiangsu provinces.
      Risk assessment maps were created by combining the bird migration routes in
      eastern China with the monthly average temperatures from May 1993 to December
      2012 nationwide. RESULTS: Among the confirmed cases, there were more men than
      women, and 50.4% were elderly adults (age >61 years). The major demographic
      groups were retirees and farmers. The temperature on the days of disease onset
      was concentrated in the range of 9 degrees C-19 degrees C; we defined 9 degrees C
      19 degrees C as the high-risk temperature range, 0 degrees C-9 degrees C or 19
      degrees C-25 degrees C as medium risk and <0 degrees C or >25 degrees C as low
      risk. The relative humidity on the days of disease onset ranged widely from 25%
      to 99%, but did not correlate with the incidence of infection. Based on the
      temperature analysis and the eastern bird migration routes, we predicted that
      after May, the high-risk region would move to the northeast and inland, while
      after September, it would move back to north China. CONCLUSIONS: Temperature and
      bird migration strongly influence the spread of the H7N9 virus. In order to
      control the H7N9 epidemic effectively, Chinese authorities should strengthen the
      surveillance of migrating birds, increase poultry and environmental sampling,
      improve live poultry selling and husbandry patterns and move from a "passive
      response pattern" to an "active response pattern" in focused preventive measures.

PMID- 24438613
TI  - Overactive bladder symptom score to evaluate efficacy of solifenacin for the
      treatment of overactive bladder symptoms.
AB  - BACKGROUND: Overactive bladder (OAB) is a series of symptoms with high prevalence
      in elderly people. This study was conducted using the overactive bladder symptom
      score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment
      of OAB. METHODS: This was a prospective, multicenter, single-arm, 12-week study
      that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin.
      Changes in OABSS, symptoms from voiding diary, perception of bladder condition
      (PPBC) score, international prostate symptom score (IPSS) and quality of life
      (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and
      PPBC score or parameters of voiding diary was also evaluated. RESULTS: At
      baseline, the mean OABSS for all patients was 9.41 +/- 2.40, and was reduced
      significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore,
      PPBC score, IPSS, and QOL were also significantly reduced during the study (P <
      0.0001). The overall incidence of adverse events was 19.91% (44 cases). The
      gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of
      the cases had adverse events related to the genitourinary system. There was a
      strong correlation between OABSS and urinary symptoms that was recorded in the 3
      day voiding dairy. CONCLUSIONS: We showed that solifenacin was clinically
      effective for relieving OAB symptoms, considering the balance between efficacy,
      patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a
      single score and can be a useful tool for research and clinical practice.

PMID- 24438614
TI  - Efficacy and safety of icotinib in Chinese patients with advanced non-small cell
      lung cancer after failure of chemotherapy.
AB  - BACKGROUND: The preclinical experiments and several clinical studies showed
      icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC)
      who failed previous chemotherapy. We performed a retrospective study of the
      efficacy and safety of icotinib monotherapy in a different and more recent sample
      of Chinese patients. METHODS: The clinical data of 149 patients with advanced
      NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July
      31, 2012 were retrospectively analyzed. All patients were given icotinib
      treatment after the failure of previous chemotherapy. Univariate and multivariate
      analyses were conducted based on the Kaplan Meier method and Cox proportional
      hazards model. RESULTS: The objective response rate was 33/149 and disease
      control rate was 105/149. No complete response occurred. Median progression free
      survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55).
      Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate
      analysis showed that the mutation of EGFR and one regimen of prior chemotherapy
      were significantly associated with longer PFS. At least one drug related adverse
      event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and
      reversible and none grade 4 toxicity. CONCLUSIONS: Icotinib monotherapy is an
      effective and well tolerated regimen for Chinese patients with NSCLC after the
      failure of chemotherapy. It is a promising agent and further study with icotinib
      in properly conducted trials with larger patient samples and other ethnic groups
      is warranted.

PMID- 24438615
TI  - Validation and target gene screening of hsa-miR-205 in lung squamous cell
      carcinoma.
AB  - BACKGROUND: Lung cancers are classified as squamous cell carcinoma (SQ),
      adenocarcinoma (AC) and small cell lung carcinoma (SCLC). SQ is the major subtype
      of lung cancer. Currently, there are no targeted therapies for SQ due to lack of
      understanding its driving oncogenes. In this study, we validated an SQ specific
      biomarker hsa-miR-205 in Chinese patients with lung cancer and screened its
      candidate target genes for further functional studies to enrich knowledge in SQ
      target therapies. METHODS: Quantitative reverse-transcription PCR (quantitative
      RT-PCR) was performed on 197 macro-dissected (cancerous cells >75%) surgical lung
      tissues (45 SQ, 44 AC, 54 SCLC and 54 adjacent normal tissues) to validate the
      expression profiles of miR-205. Furthermore, the targets of this microRNA were
      predicted through the gateway miRecords and mapped to lung cancer-associated
      pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Then
      quantitative RT-PCR was performed on an independent cohort of 44 snap-frozen
      surgical lung tissues to concurrently assess the expression profiles of miR-205
      and its 52 putative targeted genes. RESULTS: MicroRNA-205 yielded high diagnostic
      accuracy in discriminating SQ from AC with an area under the curve (AUC) of
      0.985, and discriminating SQ from SCLC with an AUC of 0.978 in formalin-fixed
      paraffin-embedded (FFPE) surgical lung tissues. Predicted targets of miR-205 were
      associated with 52 key members of lung cancer signaling pathways. Ten target
      genes (ACSL1, AXIN2, CACNA2D2, FOXO3, PPP1R3A, PRKAG3, RUNX1, SMAD4, STK3 and
      TBL1XR1) were significantly down-regulated in SQ and had a strong negative
      correlation with miR-205, while one target gene (CDH3) was up-regulated in SQ and
      exhibited a strong positive correlation with miR-205. CONCLUSIONS: We confirmed
      the high diagnostic accuracy of miR-205 in discriminating SQ from AC and SCLC in
      Chinese patients. Moreover, we identified 11 significant target genes of miR-205
      which could be used for further functional studies as the basis for the
      development of SQ targeted therapies.

PMID- 24438616
TI  - Preliminary experience with transperitoneal laparoendoscopic single-site radical
      nephrectomy using a home-made single-port device in China.
AB  - BACKGROUND: Laparoendoscopic single-site (LESS) surgery represents a technique to
      further reduce morbidity and scarring associated with surgery. We present our
      preliminary experience with transperitoneal LESS radical nephrectomy (RN) using a
      home-made single-port device in China. METHODS: From July 2010 to November 2011,
      eleven patients with renal tumor not greater than T2 underwent LESS-RN by an
      experienced laparoscopic surgeon. A home-made single-port device was used through
      a 5-cm umbilical incision. A combination of standard and articulating
      laparoscopic instruments was used. The sequence of steps of LESS-RN was similar
      to transperitoneal laparoscopic RN. Patient characteristics, perioperative
      variables and postoperative outcomes were recorded and analyzed. RESULTS: Except
      for two transperitoneal laparoscopic conversions and one hand-assisted
      laparoscopic conversion, the other procedures were completed successfully without
      conversion to open surgery. The mean operative time was 224.5 (155-297) minutes,
      estimated blood loss was 270.9 (50-900) ml, and hospital stay was 10.4 (5-15)
      days. The mean visual analog pain scale (VAPS) on the first postoperative day was
      4.0/10. Final pathological analysis revealed renal cell carcinoma in all cases
      with a stage distribution of three T1a, five T1b, and three T2a tumors. With the
      mean follow-up period of 21.4 (12-28) months, all patients were alive without
      evidence of tumor recurrence or metastasis, and were satisfied with the
      appearance of the scars. CONCLUSION: Transperitoneal LESS-RN using a home-made
      single-port device is technically feasible and safe in a selected group of
      patients (low body mass index and stage tumor) and has excellent cosmetic
      results. Although preliminary oncologic outcome is not compromised, the long-term
      evaluation of these patients is awaited.

PMID- 24438617
TI  - Expression of partial tandem duplication of mixed lineage leukaemia in patients
      with acute leukaemia and their relatives.
AB  - BACKGROUND: Partial tandem duplication of mixed lineage leukaemia (MLL-PTD) is
      detected both in patients with acute leukemia and in healthy people. However, MLL
      PTD in relatives of patients with MLL-PTD has not been reported. The objective of
      this study was to investigate the expression of MLL-PTD in patients with acute
      leukemia and in their relatives. METHODS: The bone marrow or peripheral blood was
      collected from patients with acute leukaemia and their relatives. Nested reverse
      transcription-polymerase chain reaction (RT-PCR) was applied to detect the mRNA
      expression of the MLLPTD fused gene, and further confirm in genomic DNA level.
      RESULTS: Analysing MLL-PTD in case 1, the patient's older brother and his younger
      brother were positive, while his mother and his son were negative. The exon type
      in case 1 was e9/3 fusion, but in his older brother, it was e9/3 and e11/3
      fusion, and in his younger brother, it was e9/3, e10/3, and e11/3 fusion. MLL-PTD
      in case 2 was negative, but in the patient's older sister was positive, and the
      exon type was e9/3, e10/3, and e11/3. CONCLUSIONS: The expression of MLL-PTD was
      present in cases with acute leukaemia with a single expression type. However,
      various expression types were detected in their healthy relatives. MLL-PTD can
      couple with other chromosome aberrations, and its impact on disease prognosis
      remains to be studied further.

PMID- 24438618
TI  - The percentage of peripheral blood blasts on day 7 of induction chemotherapy
      predicts response to therapy and survival in patients with acute myeloid
      leukemia.
AB  - BACKGROUND: Rapid clearance of peripheral blood blasts (PBBs) predicts complete
      remission (CR) and survival in patients with acute myeloid leukemia (AML). We
      aimed to explore the correlation between induction therapy response, outcome, and
      the PBB percentage. METHODS: Forty-six consecutive patients with de novo AML
      (excluding acute promyelocytic leukemia) were enrolled in this study. Flow
      cytometry was performed to identify cells with a leukemia-associated aberrant
      immunophenotype in the initial bone marrow aspirate and in peripheral blood on
      day 7 of induction therapy. RESULTS: The PBB percentage on day 7 (D7PBBP) was
      significantly lower in patients who achieved CR (0.03% (0.0%, 0.45%)) than in
      those who did not (10.85% (1.13%, 19.38%); u = -3.92, P < 0.001). The CR rate was
      significantly higher among patients with a D7PBBP of <0.945% (84.62%, 22/26) than
      among those with a D7PBBP of = 0.945% (25.0%, 5/20; chi2 = 16.571, P < 0.001).
      D7PBBP was significantly correlated with overall survival (OS; r = -0.437, P =
      0.003) and relapsefree survival (RFS; r = -0.388, P = 0.007). OS and RFS were
      significantly higher in patients with a D7PBBP of <0.43% than in those with a
      D7PBBP of >= 0.43% (P < 0.001 and P = 0.039, respectively). D7PBBP was also found
      to be an independent prognostic indicator in multivariate analysis for both OS (P
      = 0.036) and RFS (P = 0.035). CONCLUSION: D7PBBP may be an important risk factor
      for the achievement of complete remission, for overall survival, and for relapse
      free survival.

PMID- 24438619
TI  - Epstein-Barr virus-encoded RNAs as a survival predictor in nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection is one of the most important
      factors of nasopharyngeal carcinoma (NPC) endemic areas. Transcription of EBV
      encoded non-polyadenylated RNAs (EBERs) are presented in most of NPC tumors.
      Exploring EBERs as a prognostic marker for NPC might further be informative about
      the biology and the progression of the disease. The aim of this study was to
      analyze the role of EBV latency in the clinical management of nasopharyngeal
      carcinoma (NPC), by detecting EBERs. METHODS: RNA in situ hybridization (ISH) for
      detecting EBERs was carried out on 908 NPC tumor tissues. Overall survival (OS)
      curves were analyzed with the Kaplan-Meier method and the Cox proportional
      hazards regression models. RESULTS: The median follow-up time was 70 months (1
      120 months). Eight hundred and sixteen (89.9%) from a total of 908 consecutive
      NPC cases were found to be EBV-EBER positive. EBER-ISH staining revealed nuclear
      localization in NPC cells. In the Kaplan-Meier analysis for OS, high EBER
      expression levels in NPC patients were statistically significant positive
      prognostic factors for survival (log-rank, P = 0.022), especially in adults aged
      17-40 years (P = 0.023) and in those with advanced stage disease (log-rank, P =
      0.002). Cox proportional-hazards regression model analysis showed that the EBER
      expression level was an independent risk factor for OS (hazard ratio 0.724, P =
      0.005). CONCLUSIONS: EBERs were frequently detected in NPC tumor tissues, and
      high-level EBER expression correlated with good prognosis in NPC patients,
      especially in adult patients and in those with advanced stage disease. EBER may
      serve as a potential prognostic predictor in NPC.

PMID- 24438620
TI  - An alternative therapy for drug-resistant epilepsy: transcutaneous auricular
      vagus nerve stimulation.
AB  - BACKGROUND: Previous studies demonstrated that vagus nerve stimulation (VNS) is
      an effective therapy for drug-resistant epilepsy. Acupuncture is also used to
      treat epilepsy. This study was designed to examine the safety and effectiveness
      of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with
      drug-resistant epilepsy. METHODS: A total of 50 volunteer patients with drug
      resistant epilepsy were selected for a random clinical trial to observe the
      therapeutic effect of ta-VNS. The seizure frequency, quality of life, and
      severity were assessed in weeks 8, 16, and 24 of the treatment according to the
      percentage of seizure frequency reduction. RESULTS: In the pilot study, 47 of the
      50 epilepsy patients completed the 24-week treatment; three dropped off. After 8
      week treatment, six of the 47 patients (12%) were seizure free and 12 (24%) had a
      reduction in seizure frequency. In week 16 of the continuous treatment, six of
      the 47 patients (12%) were seizure free; 17 (34%) had a reduction in seizure
      frequency. After 24 weeks' treatment, eight patients (16%) were seizure free; 19
      (38%) had reduced seizure frequency. CONCLUSION: Similar to the therapeutic
      effect of VNS, ta-VNS can suppress epileptic seizures and is a safe, effective,
      economical, and widely applicable treatment option for drug-resistant epilepsy.
      (ChiCTR-TRC-10001023).

PMID- 24438621
TI  - Correlation between magnetic resonance T2 image signal intensity ratio and cell
      apoptosis in a rabbit spinal cord cervical myelopathy model.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) is a common cause of disability
      in elderly patients. Previous studies have shown that spinal cord cell apoptosis
      due to spinal cord compression plays an important role in the pathology of
      myelopathy. Although changes in magnetic resonance imaging (MRI) T2 signal
      intensity ratio (SIR) are considered to be an indicator of CSM, little
      information is published supporting the correlation between changes in MRI signal
      and pathological changes. This study aims to testify the correlation between MRI
      T2 SIR changes and cell apoptosis using a CSM animal model. METHODS: Forty-eight
      rabbits were randomly assigned to four groups: one control group and three
      experimental chronic compression groups, with each group containing 12 animals.
      Chronic compression of the cervical spinal cord was implemented in the
      experimental groups by implanting a screw in the C3 vertebra. The control group
      underwent sham surgery. Experimental groups were observed for 3, 6, or 9 months
      after surgery. MRI T2-weighted SIR Tarlov motor scores and cortical somatosensory
      evoked potentials (CSEPs) were periodically monitored. At each time point,
      rabbits from one group were sacrificed to determine the level of apoptosis by
      histology (n = 6) and Western blotting (n = 6). RESULTS: Tarlov motor scores in
      the compression groups were lower at all time points than the control group
      scores, with the lowest score at 9 months (P < 0.001). Electrophysiological
      testing showed a significantly prolonged latency in CSEP in the compression
      groups compared with the control group. All rabbits in the compression groups
      showed higher MRI T2 SIR in the injury epicenter compared with controls, and
      higher SIR was also found at 9 months compared with 3 or 6 months. Histological
      analysis showed significant apoptosis in the spinal cord tissue in the
      compression groups, but not in the control group. There were significant
      differences in apoptosis degree over time (P < 0.001), with the 9-month group
      displaying the most severe spinal cord apoptosis. Spearman's rank correlation
      test showed that there was close relation between MRI SIR and degree of caspase-3
      expression in Western blotting (r = 0.824. P < 0.001). CONCLUSIONS: Clear
      apoptosis of spinal cord tissue was observed during chronic focal spinal
      compression. Changes in MRI T2 SIR may be related to the severity of the
      apoptosis in cervical spinal cord.

PMID- 24438622
TI  - Differentiation of adipose-derived stem cells toward nucleus pulposus-like cells
      induced by hypoxia and a three-dimensional chitosan-alginate gel scaffold in
      vitro.
AB  - BACKGROUND: Injectable three-dimensional (3D) scaffolds have the advantages of
      fluidity and moldability to fill irregular-shaped defects, simple incorporation
      of bioactive factors, and limited surgical invasiveness. Adipose-derived stem
      cells (ADSCs) are multipotent and can be differentiated toward nucleus pulposus
      (NP)-like cells. A hypoxic environment may be important for differentiation to NP
      like cells because the intervertebral disc is an avascular tissue. Hence, we
      investigated the induction effects of hypoxia and an injectable 3D chitosan
      alginate (C/A) gel scaffold on ADSCs. METHODS: The C/A gel scaffold consisted of
      medical-grade chitosan and alginate. Gel porosity was calculated by liquid
      displacement method. Pore microstructure was analyzed by light and scanning
      electron microscopy. ADSCs were isolated and cultured by conventional methods.
      Passage 2 BrdU-labeled ADSCs were co-cultured with the C/A gel. ADSCs were
      divided into three groups (control, normoxia-induced, and hypoxia-induced
      groups). In the control group, cells were cultured in 10% FBS/DMEM. Hypoxia
      induced and normoxia-induced groups were induced by adding transforming growth
      factor-beta1, dexamethasone, vitamin C, sodium pyruvate, proline, bone
      morphogenetic protein-7, and 1% ITS-plus to the culture medium and maintaining in
      2% and 20% O2, respectively. Histological and morphological changes were observed
      by light and electron microscopy. ADSCs were characterized by flow cytometry.
      Cell viability was investigated by BrdU incorporation. Proteoglycan and type II
      collagen were measured by safranin O staining and the Sircol method,
      respectively. mRNA expression of hypoxia-inducing factor-1alpha (HIF-1alpha),
      aggrecan, and Type II collagen was determined by reverse transcription-polymerase
      chain reaction. RESULTS: C/A gels had porous exterior surfaces with 80.57%
      porosity and 50-200 um pore size. Flow cytometric analysis of passage 2 rabbit
      ADSCs showed high CD90 expression, while CD45 expression was very low. The
      morphology of induced ADSCs resembled that of NP cells. BrdU immunofluorescence
      showed that most ADSCs survived and proliferated in the C/A gel scaffold.
      Scanning electron microscopy showed that ADSCs grew well in the C/A gel scaffold.
      ADSCs in the C/A gel scaffold were positive for safranin O staining. Hypoxia
      induced and normoxia-induced groups produced more proteoglycan and Type II
      collagen than the control group (P < 0.05). Proteoglycan and Type II collagen
      levels in the hypoxia-induced group were higher than those in the normoxia
      induced group (P < 0.05). Compared with the control group, higher mRNA expression
      of HIF-1alpha, aggrecan, and Type II collagen was detected in hypoxia-induced and
      normoxiainduced groups (P < 0.05). Expression of these genes in the hypoxia
      induced group was significantly higher than that in the normoxia-induced group (P
      < 0.05). CONCLUSION: ADSCs grow well in C/A gel scaffolds and differentiate
      toward NP-like cells that produce the same extracellular matrix as that of NP
      cells under certain induction conditions, which is promoted in a hypoxic state.

PMID- 24438623
TI  - Ectopic osteogenesis and scaffold biodegradation of tissue engineering bone
      composed of chitosan and osteo-induced bone marrow mesenchymal stem cells in
      vivo.
AB  - BACKGROUND: Chitosan (CS) scaffolds combined with osteogenically induced bone
      marrow mesenchymal stem cells (BMSCs) have been proved to be promising
      substitutes for repairing bone defects. Nevertheless, the bone-forming and
      scaffold-biodegrading processes are seldom studied. This study aimed to determine
      the osteogenic ability of CS/osteo-induced BMSC composites by observing the bone
      forming process and explore the relationship between bone formation and scaffold
      biodegradation. METHODS: The CS/osteo-induced BMSC composites (CS+cells group)
      and the CS scaffolds (CS group) were, respectively, implanted into SD rat thigh
      muscles. At 2, 4, 6, 8, and 12 weeks postoperatively, the rat femurs were scanned
      by CT, and the CT values of the implants were measured and comparatively
      analyzed. Subsequently, the implants were harvested and stained with hematoxylin
      and eosin and Masson trichrome, and the percentages of bone area, scaffold area,
      and collagen area were calculated and compared between the two groups. RESULTS:
      The imaging results showed that the densities of implants of the two groups
      gradually increased along with time, but the CT values of implants in the
      CS+cells group were much higher than in the CS group at the same time point (P <
      0.05). The histological results showed that the de novo bone and collagen formed
      in the pores of the scaffolds and gradually increased since 2 weeks postoperation
      in both groups, and the scaffold gradually degraded along with the boneforming
      process. However, the comparative analysis results showed that the CS+cells group
      gained more de novo bone and collagen formation and had less scaffold than the CS
      group at the same time point (P < 0.05). CONCLUSION: The CS/osteo-induced BMSC
      composites are excellent bone tissue engineering substitutes, and the scaffold
      biodegradation is accordant with the bone formation.

PMID- 24438624
TI  - Human adipose-derived mesenchymal stem cells: a better cell source for nervous
      system regeneration.
AB  - BACKGROUND: In order to suggest an ideal source of adult stem cells for the
      treatment of nervous system diseases, MSCs from human adipose tissue and bone
      marrow were isolated and studied to explore the differences with regard to cell
      morphology, surface markers, neuronal differentiation capacity, especially the
      synapse structure formation and the secretion of neurotrophic factors. METHODS:
      The neuronal differentiation capacity of human mesenchymal stem cells from
      adipose tissue (hADSCs) and bone marrow (hBMSCs) was determined based on nissl
      body and synapse structure formation, and neural factor secretion function.
      hADSCs and hBMSCs were isolated and differentiated into neuron-like cells with
      rat brain-conditioned medium, a potentially rich source of neuronal
      differentiation promoting signals. Specific neuronal proteins and neural factors
      were detected by immunohistochemistry and enzyme-linked immunosorbent assay
      analysis, respectively. RESULTS: Flow cytometric analysis showed that both cell
      types had similar phenotypes. Cell growth curves showed that hADSCs proliferated
      more quickly than hBMSCs. Both kinds of cells were capable of osteogenic and
      adipogenic differentiation. The morphology of hADSCs and hBMSCs changed during
      neuronal differentiation and displayed neuron-like cell appearance after 14 days'
      differentiation. Both hADSCs and hBMSCs were able to differentiate into neuron
      like cells based on their production of neuron specific proteins including beta
      tubulin-III, neuron-specific enolase (NSE), nissl bodies, and their ability to
      secrete brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF).
      Assessment of synaptop hysin and growth-associated protein-43 (GAP-43) suggested
      synapse structure formation in differentiated hADSCs and hBMSCs. CONCLUSIONS: Our
      results demonstrate that hADSCs have neuronal differentiation potential similar
      to hBMSC, but with a higher proliferation capacity than hBMSC. Adipose tissue is
      abundant, easily available and would be a potential ideal source of adult stem
      cells for neural-related clinical research and application.

PMID- 24438625
TI  - Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in
      rats with chronic hypoxia induced pulmonary hypertension.
AB  - BACKGROUND: Phosphatase and tensin homologue on chromosome ten (PTEN) acts as a
      convergent nodal signalling point for cardiomyocyte hypertrophy, growth and
      survival. However, the role of PTEN in cardiac conditions such as right
      ventricular hypertrophy caused by chronic hypoxic pulmonary, hypertension remains
      unclear. This study preliminarily discussed the role of PTEN in the cardiac
      response to increased pulmonary vascular resistance using the hypoxia-induced PH
      rats. METHODS: Male Sprague Dawley rats were exposed to 10% oxygen for 1, 3, 7,
      14 or 21 days to induce hypertension and right ventricular hypertrophy. Right
      ventricular systolic pressure was measured via catheterization. Hypertrophy index
      was calculated as the ratio of right ventricular mass to left ventricle plus
      septum mass. Tissue morphology and fibrosis were measured using hematoxylin,
      eosin and picrosirius red staining. The expression and phosphorylation levels of
      PTEN in ventricles were determined by real time PCR and Western blotting.
      RESULTS: Hypoxic exposure of rats resulted in pathological hypertrophy,
      interstitial fibrosis and remodelling of the right ventricle. The phosphorylation
      of PTEN increased significantly in the hypertrophic right ventricle compared to
      the normoxic control group. There were no changes in protein expression in either
      ventricle. CONCLUSION: Hypoxia induced pulmonary hypertension developed
      pathological right ventricular hypertrophy and remodelling probably related to an
      increased phosphorylation of PTEN.

PMID- 24438626
TI  - Effect of surfactant protein A on lipopolysaccharide-induced tumor necrosis
      factor-alpha expression in human proximal tubular epithelial cells.
AB  - BACKGROUND: Surfactant protein A (SP-A) contributes to the regulation of sepsis
      induced acute lung injury. In a previous study, we demonstrated the expression
      and localization of SP-A in the kidneys. The present study evaluated the effect
      of SP-A on lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-alpha)
      expression and its underlying mechanisms in the human renal tubular epithelial
      (HK-2) cells. METHODS: Indirect immunofluorescence assay was used to detect SP-A
      distribution and expression in HK-2 cells. HK-2 cells were treated with various
      concentrations of LPS (0, 0.1, 1, 2, 5, and 10 mg/L) for 8 hours and with 5 mg/L
      LPS for different times (0, 2, 4, 8, 16, and 24 hours) to determine the effects
      of LPS on SP-A and TNF-alpha expression. Then, HK-2 cells were transfected with
      SP-A siRNA to analyze nuclear factor kappaB (NF-kappaB) P65 and TNF-alpha
      expression of HK-2 cells after LPS-treatment. RESULTS: Indirect
      immunofluorescence assay revealed that SP-A is localized to the membrane and
      cytoplasm of HK-2 cells. Interestingly, SP-A1/SP-A2 and TNF-a expression were
      found to be significantly increased in HK-2 cells upon LPS treatment.
      Transfection of LPS-treated HK-2 cells with SP-A siRNA resulted in significant
      increases in the levels of NF-kappaB P65 protein and TNF-alpha mRNA and protein
      compared to those in non-transfected LPS-treated HK-2 cells. CONCLUSION: SP-A
      plays an important role in protecting cells against sepsis-induced acute kidney
      injury by inhibiting NF-kappaB activity to modulate LPS-induced increase in TNF
      alpha expression.

PMID- 24438627
TI  - Application of a three-dimensional microsurgical video system for a rat femoral
      vessel anastomosis.
AB  - BACKGROUND: The operating microscopes have been applied to modern surgery for
      nearly a century. However, generations of microsurgeons have to flex their necks
      and fix their eyes on the eyepieces of a microscope continually that leads to
      physical and mental fatigue during a long operation. Stereoscopic three
      dimensional (3D) media provides more ergonomic working environment, subsequently,
      resulting better performance in tasks and more accurate judgment. In this study,
      an alternative method of magnification was analyzed using a three-dimensional
      microsurgical video system and compared with the traditional method under
      microscopy to evaluate the availability and feasibility of a 3D microsurgical
      video system for microvascular anastomosis. METHODS: Forty Sprague-Dawley rats
      were randomly divided into four groups with each of 10. In 20 rats, 10 femoral
      artery anastomoses with a conventional microscope (arterial microscope group)
      were compared with that of 10 femoral artery anastomoses with a 3D microsurgical
      video system (arterial 3D group). For the other 20 rats, 10 femoral vein
      anastomoses using a conventional microscope (venous microscope group) were
      compared with that of 10 femoral vein anastomoses using a 3D microsurgical video
      system (venous 3D group). The arterial and venous microscope groups were
      considered to be the control groups. The arterial and venous 3D groups were the
      experimental groups. The examined criteria were as follows: anastomotic time,
      patency right after the procedure and 10 days later, number of sutures, vessel
      caliber, and pathological features. RESULTS: There were no differences between
      the operating equipment with respect to vessel caliber, anastomotic time, patency
      rate, number of sutures, and pathological changes in either the small arteries or
      veins. The average arterial anastomotic time of the arterial microscope group and
      arterial 3D group was 34.21 and 33.87 minutes, respectively (P > 0.05). The
      average venous anastomotic time of the venous microscope group and venous 3D
      group was 29.95 and 31.50 minutes, respectively (P > 0.05). CONCLUSIONS: A small
      vessel anastomosis can be performed successfully with the help of a 3D display
      system. Although the vascular anastomotic time did not demonstrate a significant
      difference between the groups, the 3D microsurgical video system offers another
      option to improve the working environment for surgeons. Further development of
      our 3D monitoring system should focus on a higher resolution and better
      flexibility.

PMID- 24438628
TI  - Insulin enhances apoptosis induced by cisplatin in human esophageal squamous cell
      carcinoma EC9706 cells related to inhibition of autophagy.
AB  - BACKGROUND: Chemoresistance is common among patients with esophageal squamous
      cell carcinoma (ESCC). We investigated the effect and mechanism of insulin on
      enhancing anticancer functions of cisplatin in human esophageal cancer cell line
      EC9706. METHODS: The viability of EC9706 cells exposed to cisplatin was assessed
      using MTT assay. The times T1, when the number of living cells reached a plateau
      and T2, when the number of living cells reached a new plateau after the addition
      of insulin were found. T1 and T2 plateau cells were stained by Annexin V-FITC/PI
      and monodansylcadaverin (MDC). Fluorescent microscopy was used to observe the
      expression of apoptosis and autophagy intuitively. Apoptotic ratio and
      fluorescent intensity were analysed by flow cytometry (FCM) quantitatively.
      Western blotting analysis was used to estimate the protein expression levels of
      AKT, mTOR, PI3K, PTEN, autophage related indicator LC3-II and autophage related
      protein Beclin1 changes that occurred in the course of treatment. RESULTS: A
      larger number of typical autophagosomes were detected in EC9706 cells exposed to
      cisplatin. Insulin can increase the apoptosis induced by cisplatin. Apoptotic
      ratio of T1 plateau cells ((32.6 +/- 4.3)%) is significantly less than T2 plateau
      ((47.5 +/- 5.6)%). MDC fluorescent intensity at T1 plateau (104.9 +/- 13.2) was
      significantly higher than intensity at T2 plateau (82.6 +/- 10.3). After
      cotreatment with insulin, the expression level of LC3-II, Beclin1 and PTEN in T2
      plateau cells were significantly downregulated, but AKT, mTOR and PI3K
      expressions significantly upregulated compared with T1 plateau. CONCLUSIONS:
      Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous
      cell carcinoma EC9706 cells related to inhibition of autophagy. The activation of
      PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of
      autophagy in EC9706 cells, which may be attributed to the anticancer effects of
      cisplatin.

PMID- 24438629
TI  - Validation of glaucoma-like features in the rat episcleral vein cauterization
      model.
AB  - BACKGROUND: Glaucoma, an irreversible optic nerve neuropathy, always results in
      blindness. This study aimed to evaluate glaucoma-like features in the rat
      episcleral vein cauterization (EVC) model by multiple in vivo and in vitro
      evidences. METHODS: Wistar rat was used in this study. The elevated intraocular
      pressure (IOP) was induced by cauterization of three episcleral veins. IOP was
      monitored with Tono-Pen XL tonometer. Time-dependent changes to the neuronal
      retinal layers were quantified by Fourier domain-optical coherence tomography.
      The function of retina was evaluated by electroretinogram (ERG). Survival of
      retinal ganglion cells (RGCs) was quantified by retrograde labeling. Histology
      study was performed with retinal sections stained with hematoxylin-eosin, glial
      fibrillary acidic protein, and neuronal nuclear antigen. Retina and aqueous humor
      protein were extracted and cytotoxic protein tumor necrosis factor alpha (TNF
      alpha) and alpha-2 macroglobulin (alpha2m) were measured with Western blotting.
      RESULTS: EVC is a relatively facile intervention, with low failure rates (<5%).
      After surgical intervention, chronic mild IOP elevation (about 1.6-fold over
      normal, P < 0.05) was induced for at least 6 weeks without requiring a second
      intervention. High IOP causes chronic and progressive loss of RGCs (averaging
      about 4% per week), progressive thinning of neuronal retinal layers (3-5 MUm per
      week), and reduction of a- and b-wave in ERG. EVC method can also induce glial
      cell activation and alterations of inflammation proteins, such as TNF-alpha and
      alpha2m. CONCLUSION: EVC method can establish a robust, reliable, economic and
      highly reproducible glaucomatous animal model.

PMID- 24438630
TI  - Vitamin D receptor and its protective role in diabetic nephropathy.
AB  - OBJECTIVE: To review the advances of studies on vitamin D receptor and its role
      in the pathogenesis of diabetic nephropathy. DATA SOURCES: A comprehensive search
      of the PubMed literatures without restriction on the publication date was carried
      out using keywords such as vitamin D receptor and diabetic nephropathy. STUDY
      SELECTION: Articles related to vitamin D receptor and diabetic nephropathy were
      selected and carefully analyzed. RESULTS: The ligands as well as construction and
      tissue distribution of vitamin D receptor were summarized. Pathogenesis of
      diabetic nephropathy was analyzed. The mechanisms underlying the renoprotective
      role of vitamin D receptor including inhibition of renin-angiotensin system, anti
      inflammation, anti-fibrosis and the reduction of proteinuria were reviewed.
      Mounting evidences from animal and clinical studies have suggested that vitamin D
      therapy has beneficial effects on the renal systems and the underlying
      renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways
      is a hot research topic. CONCLUSION: Our study suggests that vitamin D receptor
      has a great potential for preventing the progression of diabetic nephropathy via
      multiple mechanisms.

PMID- 24438631
TI  - Pig islets for islet xenotransplantation: current status and future perspectives.
AB  - OBJECTIVE: To review the current status and progress on pig islet
      xenotransplantation. DATA SOURCES: Data used in this review were mainly from
      English literature of Pubmed database. The search terms were "pig islet" and
      "xenotransplantation". STUDY SELECTION: The original articles and critical
      reviews selected were relevant to this review's theme. RESULTS: Pigs are
      suggested to be an ideal candidate for obtaining available islet cells for
      transplantation. However, the potential clinical application of pig islet is
      still facing challenges including inadequate yield of high-quality functional
      islets and xenorejection of the transplants. The former can be overcome mainly by
      selection of a suitable pathogen-free source herd and the development of
      isolation and purification technology. While the feasibility of successful
      preclinical pig islet xenotranplantation provides insights in the possible
      mechanisms of xenogeneic immune recognition and rejection to overwhelm the
      latter. In addition, the achievement of long-term insulin independence in
      diabetic models by means of distinct islet products and novel immunotherapeutic
      strategies is promising. CONCLUSIONS: Pig islet xenotransplantation is one of the
      prospective treatments to bridge the gap between the needs of transplantation in
      patients with diabetes and available islet cells. Nonetheless, further studies
      and efforts are needed to translate obtained findings into tangible applications.

PMID- 24438632
TI  - Effect of Maotai liquor on P53 gene in primary hepatocellular carcinoma induced
      by compound factors in rats.

PMID- 24438633
TI  - Comparison of proliferation index between nestin-positive cells and glial
      fibrillary acidic protein-positive cells in human astrocytic tumors.

PMID- 24438634
TI  - No genetic alterations in infants from intracytoplasmic sperm injection in
      combination with artificial oocyte activation: a pilot study.

PMID- 24438635
TI  - Dermatofibrosarcoma protuberans of the chest wall: three-dimensional wide
      excision and reconstruction.

PMID- 24438636
TI  - Non-vascularized fibular graft for distal radial reconstruction: 42 years follow
      up.

PMID- 24438637
TI  - Successful term pregnancy after laparoscopic surgery of low grade endometrial
      stromal sarcoma.

PMID- 24438638
TI  - Scalp metastasis from gallbladder cancer: an unusual case.

PMID- 24438639
TI  - Recurrent acute coronary syndrome with Takayasu arteritis.

PMID- 24438640
TI  - HIV seroconversion manifesting as Guillian-Barre syndrome.

PMID- 24438641
TI  - Acute ST-elevation myocardial infarction in a patient with polycythemia vera.

PMID- 24438642
TI  - Fatal hemorrhea due to ascending aorta pseudoaneurysm rupture after Bentall
      procedure in a patient with Behcet's disease.

PMID- 24438643
TI  - Sepsis in a newborn with anterior urethral valve and urinary tract infection.

PMID- 24438644
TI  - Coverage, quality of and barriers to postnatal care in rural Hebei, China: a
      mixed method study.
AB  - BACKGROUND: Postnatal care is an important link in the continuum of care for
      maternal and child health. However, coverage and quality of postnatal care are
      poor in low- and middle-income countries. In 2009, the Chinese government set a
      policy providing free postnatal care services to all mothers and their newborns
      in China. Our study aimed at exploring coverage, quality of care, reasons for not
      receiving and barriers to providing postnatal care after introduction of this new
      policy. METHODS: We carried out a mixed method study in Zhao County, Hebei
      Province, China from July to August 2011. To quantify the coverage, quality of
      care and reasons for not using postnatal care, we conducted a household survey
      with 1601 caregivers of children younger than two years of age. We also conducted
      semi-structured interviews with 24 township maternal and child healthcare workers
      to evaluate their views on workload, in-service training and barriers to
      postnatal home visits. RESULTS: Of 1442 (90% of surveyed caregivers) women who
      completed the postnatal care survey module, 8% received a timely postnatal home
      visit (within one week after delivery) and 24% of women received postnatal care
      within 42 days after delivery. Among women who received postnatal care, 37%
      received counseling or guidance on infant feeding and 32% on cord care. 24% of
      women reported that the service provider checked jaundice of their newborns and
      18% were consulted on danger signs and thermal care of their newborns. Of 991
      mothers who did not seek postnatal care within 42 days after birth, 65% of them
      said that they did not knew about postnatal care and 24% of them thought it was
      unnecessary. Qualitative findings revealed that staff shortages and inconvenient
      transportation limited maternal and child healthcare workers in reaching out to
      women at home. In addition, maternal and child healthcare workers said that in
      service training was inadequate and more training on postnatal care, hands-on
      practice, and supervision were needed. CONCLUSIONS: Coverage and quality of
      postnatal care were low in rural Hebei Province and far below the targets set by
      Chinese government. We identified barriers both from the supply and demand side.

PMID- 24438645
TI  - Gallbladder carcinoma: a New Zealand centre's 10-year experience with
      presentation, ethnic diversity and survival rate.
AB  - BACKGROUND: Gallbladder cancer is a high-mortality cancer with a wide range of
      incidence worldwide. Some indigenous populations are known to have a higher
      incidence of gallbladder cancer. Commonly, it is incidentally discovered during
      routine gallbladder surgery. The primary aim was to determine the incidence and
      characteristics of gallbladder cancer in a New Zealand population. The secondary
      aim was to determine if inequalities in gallbladder cancer rates between Maori
      and non-Maori have decreased. METHODS: A retrospective cohort study utilizing an
      online database was conducted to identify all patients with gallbladder
      malignancy treated in the Waitemata District Health Board from 2003 to 2013. The
      outcomes measured were staging of cancer, histology, ethnicity, incidental
      finding and survival rates. RESULTS: The age-standardized incidence (ASI) rate of
      gallbladder carcinoma is 0.60/100 000. The gender-specific ASI rates were
      0.21/100 000 (men) and 0.76/100 000 (women). The incidence for Maori was 0.96/100
      000 (men) and 1.37/100 000 (women). Gallbladder carcinoma was found incidentally
      in 0.44% of cholecystectomies, which made up 46.2% of all cases. Right upper
      quadrant pain was the most common presenting symptom (74.4%). Surgery was the
      most common treatment modality (66.7%). Mean survival across all patients was
      12.24 months. CONCLUSION: Our study found that the ASI of gallbladder carcinoma
      when compared with the Koea et al. study has decreased for men from New Zealand,
      but appears to have increased slightly for women from New Zealand. The raw
      incidence for Maori men and women appears to have decreased, but inequality in
      gallbladder cancer incidence between Maori and non-Maori remains.

PMID- 24438646
TI  - Regulation of protein degradation pathways by amino acids and insulin in skeletal
      muscle of neonatal pigs.
AB  - BACKGROUND: The rapid gain in lean mass in neonates requires greater rates of
      protein synthesis than degradation. We previously delineated the molecular
      mechanisms by which insulin and amino acids, especially leucine, modulate
      skeletal muscle protein synthesis and how this changes with development. In the
      current study, we identified mechanisms involved in protein degradation
      regulation. In experiment 1, 6- and 26-d-old pigs were studied during 1)
      euinsulinemic-euglycemic-euaminoacidemic, 2) euinsulinemic-euglycemic
      hyperaminoacidemic, and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps for
      2 h. In experiment 2, 5-d-old pigs were studied during 1) euinsulinemic
      euglycemic-euaminoacidemic-euleucinemic, 2) euinsulinemic-euglycemic
      hypoaminoacidemic-hyperleucinemic, and 3) euinsulinemic-euglycemic
      euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices
      of ubiquitin-proteasome, i.e., atrogin-1 (MAFbx) and muscle RING-finger protein-1
      (MuRF1) and autophagy-lysosome systems, i.e., unc51-like kinase 1 (UKL1),
      microtubule-associated protein light chain 3 (LC3), and lysosomal-associated
      membrane protein 2 (Lamp-2). For comparison, we measured ribosomal protein S6
      (rpS6) and eukaryotic initiation factor 4E (eIF4E) activation, components of
      translation initiation. RESULTS: Abundance of atrogin-1, but not MuRF1, was
      greater in 26- than 6-d-old pigs and was not affected by insulin, amino acids, or
      leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by
      treatment. The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased
      by insulin, amino acids, and leucine. These responses were more profound in
      younger pigs. Abundance of Lamp-2 was not affected by treatment or development.
      Abundance of eIF4E, but not rpS6, was higher in 6- than 26-d-old-pigs but
      unaffected by treatment. Phosphorylation of eIF4E was not affected by treatment,
      however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and
      the responses decreased with development. CONCLUSIONS: The rapid growth of
      neonatal muscle is in part due to the positive balance between the activation of
      protein synthesis and degradation signaling. Insulin, amino acids, and,
      particularly, leucine, act as signals to modulate muscle protein synthesis and
      degradation in neonates.

PMID- 24438647
TI  - America's emergency care environment, a state-by-state Report Card: 2014 edition.

PMID- 24438648
TI  - Commentary: it's the little things that matter.

PMID- 24438649
TI  - Clinical policy: procedural sedation and analgesia in the emergency department.
AB  - This clinical policy from the American College of Emergency Physicians is the
      revision of a 2005 clinical policy evaluating critical questions related to
      procedural sedation in the emergency department.1 A writing subcommittee reviewed
      the literature to derive evidence-based recommendations to help clinicians answer
      the following critical questions: (1) In patients undergoing procedural sedation
      and analgesia in the emergency department,does preprocedural fasting demonstrate
      a reduction in the risk of emesis or aspiration? (2) In patients undergoing
      procedural sedation and analgesia in the emergency department, does the routine
      use of capnography reduce the incidence of adverse respiratory events? (3) In
      patients undergoing procedural sedation and analgesia in the emergency
      department, what is the minimum number of personnel necessary to manage
      complications? (4) Inpatients undergoing procedural sedation and analgesia in the
      emergency department, can ketamine, propofol, etomidate, dexmedetomidine,
      alfentanil and remifentanil be safely administered? A literature search was
      performed, the evidence was graded, and recommendations were given based on the
      strength of the available data in the medical literature.

PMID- 24438650
TI  - Annals of Emergency Medicine Journal Club. Treatment of calcium channel blocker
      poisoning: should we reprioritize our potpourri of treatment options?: answers to
      the September 2013 Journal Club questions.

PMID- 24438651
TI  - Change of shift. Thank you, emergency medicine.

PMID- 24438652
TI  - Images in emergency medicine. Acute intermittent porphyria.

PMID- 24438653
TI  - An unusual cause of electrocardiographic ST elevation--can the Japanese fishing
      industry help us? Takotsubo cardiomyopathy.

PMID- 24438654
TI  - Factoring in postresuscitative measures.

PMID- 24438655
TI  - In reply.

PMID- 24438656
TI  - Subluxation of clinical skills.

PMID- 24438657
TI  - In reply.

PMID- 24438658
TI  - What is the role of [11C]choline PET/CT in decision making strategy before post
      operative salvage radiation therapy in prostate cancer patients?

PMID- 24438659
TI  - Misinterpretation of the origins and composition of staging data and its impact
      on colorectal cancer survival.

PMID- 24438660
TI  - Optimal use of staging data in international comparisons of colorectal cancer
      survival.

PMID- 24438661
TI  - Dose calculation and treatment plan optimization including imaging dose from
      kilovoltage cone beam computed tomography.
AB  - BACKGROUND: With the increasing use of cone beam computed tomography (CBCT) for
      patient position verification and radiotherapy treatment adaptation, there is an
      increasing need to develop techniques that can take into account concomitant dose
      using a personalized approach. MATERIAL AND METHODS: A total of 20 patients (10
      pelvis and 10 head and neck) who had undergone radiation therapy using intensity
      modulated radiation therapy (IMRT) were selected and the dose from kV CBCT was
      retrospectively calculated using a treatment planning system previously
      commissioned for this purpose. The imaging dose was added to the CT images used
      for treatment planning and the difference in its addition prior to and after the
      planning was assessed. RESULTS: The additional isocenter dose as a result of
      daily CBCT is in the order of 3-4 cGy for 35-fraction head and neck and 23-47 cGy
      for 25-fraction pelvis cases using the standard head and neck and pelvis image
      acquisition protocols. The pelvic dose is especially dependent on patient size
      and body mass index (BMI), being higher for patients with lower BMI. Due to the
      low energy of the kV CBCT beam, the maximum energy deposition is at or near the
      surface with the highest dose being on the patient's left side for the head and
      neck (~7 cGy) and on the posterior for the pelvic cases (~80 cGy). Addition of
      imaging dose prior to plan optimization resulted in an average reduction of 4% in
      the plan monitor units and 5% in the number of control points. CONCLUSION: Dose
      from daily kV CBCT has been added to patient treatment plans using previously
      commissioned kV CBCT beams in a treatment planning system. Addition of imaging
      dose can be included in IMRT treatment plan optimization and would facilitate
      customization of imaging protocol based on patient anatomy and location of
      isocenter.

PMID- 24438662
TI  - [From Louis-Nicolas Vauquelin to Frederick Sanger: a plea for analytical
      chemistry].

PMID- 24438663
TI  - [Hospital-based health technology assessment in France: how to proceed to
      evaluate innovative medical devices?].
AB  - Innovative medical devices offer solutions to medical problems and greatly
      improve patients' outcomes. Like National Health Technology Assessment (HTA)
      agencies, hospitals face numerous requests for innovative and costly medical
      devices. To help local decision-makers, different approaches of hospital-based
      HTA (HB-HTA) have been adopted worldwide. The objective of the present paper is
      to explore HB-HTA models for adopting innovative medical devices in France and
      elsewhere. Four different models have been conceptualized: "ambassador" model,
      "mini-HTA" model, "HTA unit" model and "internal committee". Apparently, "HTA
      unit" and "internal committee" (or a mixture of both models) are the prevailing
      HB-HTA models in France. Nevertheless, some weaknesses of these models have been
      pointed out in previous works. Only few examples involving hospital pharmacists
      have been found abroad, except in France and in Italy. Finally, the harmonization
      of the assessment of innovative medical devices in France needs a better
      understanding of HB-HTA practices. 

PMID- 24438664
TI  - [Current view on gut microbiota].
AB  - Gut microbiota is more and more important since metagenomic research have brought
      new knowledge on this topic especially for human health. Firstly, gut microbiota
      is a key element for our organism he lives in symbiosis with. Secondly, it
      interacts favorably with many physiological functions of our organism. Thirdly,
      at the opposite, it can be an active participant in intestinal pathologies linked
      to a dysbiosis mainly in chronic inflammatory bowel diseases like Crohn disease
      or ulcerative colitis but also in obesity, metabolic syndrome, and more prudently
      in autism and behavioral disorders. In order to keep a good health, it is
      essential to protect our gut microbiota as soon as our young age and maintain it
      healthy. Face to a more and more important number of publications for treating
      certain digestive diseases with fecal microbial transplantation, it needs to be
      very careful and recommend further studies in order to assess risks and define
      standardized protocols. Gut microbiota metabolic capacities towards xenobiotics
      need to be developed, and we must take an interest in the modifications they
      induce on medicinal molecules. On the other hand, it is essential to study the
      potent effects of pesticides and other pollutants on microbiota functions. 

PMID- 24438665
TI  - [Study of physicochemical and bacteriological impact of a weekly assembly of
      automated compounding BAXA((r)) Exacta-Mix 2400 on parenteral nutrition admixture
      manufacturing].
AB  - INTRODUCTION: The parenteral nutrition admixtures are manufactured with an
      automated compounding BAXA((r)) Exacta-Mix 2400. A 48-hour assembly has been
      validated. To optimize time and cost, a weekly assembly was tested. MATERIALS AND
      METHODS: Assembly was made on the first day. Ten identical parenteral nutrition
      admixtures (different volumes and compositions) were produced each day. A
      macroscopic examination was done at D0, D7 and D14. Physicochemical controls
      (electrolytes determinations by atomic absorption spectrophotometry, osmolalities
      measurements) were performed. Microbiological tests included a filtration
      membrane sterility test (Steritest((r))) and a plate count agar environmental
      monitoring. RESULTS: All mixtures were considered stable. The 12 Steritest((r))
      (H24, H48, D7 and D14) did not show any bacterial or fungal contamination. No
      microorganism has been detected on the plate count agar at D4 and D7. Concerning
      the physicochemical parameters of each parental nutrition admixture, no
      significant difference (Wilcoxon test) with the first day was found. DISCUSSION
      AND CONCLUSIONS: The automated filling system BAXA((r)) Exacta-Mix 2400 improves
      the quality and safety of production. According to these results, the weekly
      assembly is validated and permit to save time (80hours/year) and cost (40 000
      euros on consumable/year).

PMID- 24438666
TI  - [Involvement of pharmacists in systems for supervising off-label medications:
      example of the CAMTEA system for the prescription of baclofen in alcohol use
      disorder in Northern France].
AB  - Off-label prescribing matches the using of medications outside the summary of
      product characteristics. Adverse drug reactions are often poorly studied in off
      label situations, which may expose patients to additional safety risks, and
      impose taking specific precautions. The current off-label prescribing practice of
      baclofen for alcohol-dependence in France is a typical illustration of such a
      situation. CAMTEA is a regional system set up in 2010 in Northern France, which
      gathers addiction and pharmacovigilance specialists, and aims at strengthening
      the prescription supervising and the monitoring of some off-label medication used
      for addictive disorders, especially baclofen. Until now, institution or office
      based pharmacists have not been implicated, whereas they engaged their liability
      when delivering off-labeled treatment and they may highly contribute to the
      patient monitoring and the spotting of adverse events. We propose hereby possible
      measures for involving pharmacists into the patient supervising system developed
      within CAMTEA. In the current French context concerning the off-label use of
      baclofen, which will be the first off-label prescribing practice to be framed by
      a new legal disposition called "temporary use recommendation", the key role of
      pharmacists should be highlighted. 

PMID- 24438667
TI  - Implementation of real-time identification analysis and quantification of
      chemotherapies preparations with a Multispec((r)) analyser.
AB  - Post-production analytic control of chemotherapies preparations remains a
      challenge for hospital pharmacists. Indeed, to be feasible, this control needs to
      be reliable, fast and easy to implement and to use on real life. This is
      particularly true for teams not familiar with analytic methods. The
      Multispec((r)) analyser has been specially manufactured for that purpose. After
      several years of daily use, we wanted to focus on its implementation, abilities
      and defects that should be corrected on the next analyser. Upon 24 months, 23,350
      samples have been analysed. Four percent have been rejected on the first
      analysis, and finally only 0.37% with another sample after homogenization. Eighty
      six preparations have been done another time for non-conformity purpose.
      Difficulties of implementation were in particular on anthracyclins,
      oxazophosphorins and monoclonal antibodies. However, compared to liquid
      chromatography for example, the ultraviolet and infrared combination allows a
      large number of drugs to be recognized and quantified fastly. As a conclusion
      this analyser is quite helpful and gives a serious alternative to post-production
      analytic control for chemotherapies preparations. Some points should however be
      improved, probably on the next analyser, for instance the sample volume necessary
      for analysis. 

PMID- 24438668
TI  - Development of a Fourier transform infrared spectroscopy coupled to UV-Visible
      analysis technique for aminosides and glycopeptides quantitation in antibiotic
      locks.
AB  - Antibiotic Lock technique maintains catheters' sterility in high-risk patients
      with long-term parenteral nutrition. In our institution, vancomycin, teicoplanin,
      amikacin and gentamicin locks are prepared in the pharmaceutical department. In
      order to insure patient safety and to comply to regulatory requirements,
      antibiotic locks are submitted to qualitative and quantitative assays prior to
      their release. The aim of this study was to develop an alternative quantitation
      technique for each of these 4 antibiotics, using a Fourier transform infrared
      (FTIR) coupled to UV-Visible spectroscopy and to compare results to HPLC or
      Immunochemistry assays. Prevalidation studies permitted to assess spectroscopic
      conditions used for antibiotic locks quantitation: FTIR/UV combinations were used
      for amikacin (1091-1115cm(-1) and 208-224nm), vancomycin (1222-1240cm(-1) and 276
      280nm), and teicoplanin (1226-1230cm(-1) and 278-282nm). Gentamicin was
      quantified with FTIR only (1045-1169cm(-1) and 2715-2850cm(-1)) due to
      interferences in UV domain of parabens, preservatives present in the commercial
      brand used to prepare locks. For all AL, the method was linear (R(2)=0.996 to
      0.999), accurate, repeatable (intraday RSD%: from 2.9 to 7.1% and inter-days
      RSD%: 2.9 to 5.1%) and precise. Compared to the reference methods, the FTIR/UV
      method appeared tightly correlated (Pearson factor: 97.4 to 99.9%) and did not
      show significant difference in recovery determinations. We developed a new simple
      reliable analysis technique for antibiotics quantitation in locks using an
      original association of FTIR and UV analysis, allowing a short time analysis to
      identify and quantify the studied antibiotics. 

PMID- 24438669
TI  - Synthesis, characterization and biological studies of substituted quinozoline-4
      (3H)-ones containing diazepine moiety.
AB  - The synthesis and characterization of new series of 1,4-benzodiazepine
      derivatives have been presented. The structures were confirmed by elemental
      analyses, IR spectral, (1)H NMR spectral and mass spectral data. All the
      compounds were screened for in vitro antimicrobial and anthelmintic activities.
      The antibacterial activity was tested against Staphylococcus aureus (Gram
      positive), Bacillus cereus (Gram positive), Escherichia coli (Gram negative) and
      Pseudomonas aeruginosa (Gram negative). The antifungal activity was tested
      against Aspergillus niger and Candida albicans. All the compounds showed
      considerable antimicrobial activity against the microorganism studied. The
      significant anthelmintic activity of all novel compounds was demonstrated against
      Pheretima posthuma. Based on the nature of substituent present, the structure
      activity correlation of novel compounds was discussed. 

PMID- 24438670
TI  - Neurosymptomatic carvenous sinus meningioma: a 15-years experience with
      fractionated stereotactic radiotherapy and radiosurgery.
AB  - BACKGROUND: The tumor removal of Cavernous Sinus Meningiomas usually results in
      severe neurological deficits. Stereotactic radiosurgery (SRS) and fractionated
      Stereotactic radiotherapy (SRT) are advanced modalities of radiotherapy for
      treatment of patients with inoperable and symptomatic CSMs. The authors evaluated
      the long term symptomatology, the image findings, and the toxicity of patients
      with CSMs treated with SRS or SRT. PATIENTS AND METHODS: From 1994 to 2009, 89
      patients with symptomatic CSMs were treated with SRS or SRT. The indication was
      based on tumour volume and or proximity to the optic chiasm. The median single
      dose of SRS was 14 Gy, while the SRT total dose, ranged from 50.4 to 54 Gy
      fractionated in 1.8-2 Gy/dose. The median follow-up period lasted 73 months.
      RESULTS: The clinical and radiological improvement was the same despite the
      method of radiotherapy; 41.6% (SRS) and 48.3% (SRT) of patients treated. The
      disease-free survivals were 98.8%, 92.3% and 92.3%, in 5, 10, and 15 years,
      respectively. There was no statistical difference in relation to the symptoms and
      image findings between both methods. According to the Common Toxicity Criteria,
      7% of the patients presented transient optic neuropathy during 3 months (grade 2)
      and recovered with dexamethasone, 2 patients had trigeminal neuropathy (grade 2)
      and improved rapidly, and one patient presented total occlusion of the internal
      carotid artery without neurological deficit (grade 2). Temporary lethargy and
      headache (grade 1) were the most frequent immediate complications. No severe
      complications occurred. CONCLUSIONS: Stereotactic Radiosurgery and fractionated
      Stereotactic Radiotherapy were equally safe and effective in the management of
      symptomatic CSMs.

PMID- 24438671
TI  - Preparation and evaluation of poly(2-hydroxyethyl aspartamide)-hexadecylamine
      iron oxide for MR imaging of lymph nodes.
AB  - The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl
      aspartamide)-C16-iron oxide (PHEA-C16-iron oxide) nanoparticles and to evaluate
      their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes.
      The PHEA-C16-iron oxide nanoparticles were synthesized by coprecipitation method.
      The core size of the PHEA-C16-iron oxide nanoparticles was about 5 to 7 nm, and
      the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous
      solution. The size of the nanoparticles was controlled by the amount of C16. The
      3.0-T MRI signal intensity of a rabbit lymph node was effectively reduced after
      intravenous administration of PHEA-C16-iron oxide with the size of 20 nm. The in
      vitro and in vivo toxicity tests revealed the high biocompatibility of PHEA-C16
      iron oxide nanoparticles. Therefore, PHEA-C16-iron oxide nanoparticles with 20-nm
      size can be potentially useful as T2-weighted MR imaging contrast agents for the
      detection of lymph nodes. 

PMID- 24438672
TI  - Validation of public health competencies and impact variables for low- and middle
      income countries.
AB  - BACKGROUND: The number of Master of Public Health (MPH) programmes in low- and
      middle-income countries (LMICs) is increasing, but questions have been raised
      regarding the relevance of their outcomes and impacts on context. Although
      processes for validating public health competencies have taken place in recent
      years in many high-income countries, validation in LMICs is needed. Furthermore,
      impact variables of MPH programmes in the workplace and in society have not been
      developed. METHOD: A set of public health competencies and impact variables in
      the workplace and in society was designed using the competencies and learning
      objectives of six participating institutions offering MPH programmes in or for
      LMICs, and the set of competencies of the Council on Linkages Between Academia
      and Public Health Practice as a reference. The resulting competencies and impact
      variables differ from those of the Council on Linkages in scope and emphasis on
      social determinants of health, context specificity and intersectoral
      competencies. A modified Delphi method was used in this study to validate the
      public health competencies and impact variables; experts and MPH alumni from
      China, Vietnam, South Africa, Sudan, Mexico and the Netherlands reviewed them and
      made recommendations. RESULTS: The competencies and variables were validated
      across two Delphi rounds, first with public health experts (N = 31) from the six
      countries, then with MPH alumni (N = 30). After the first expert round,
      competencies and impact variables were refined based on the quantitative results
      and qualitative comments. Both rounds showed high consensus, more so for the
      competencies than the impact variables. The response rate was 100%. CONCLUSION:
      This is the first time that public health competencies have been validated in
      LMICs across continents. It is also the first time that impact variables of MPH
      programmes have been proposed and validated in LMICs across continents. The high
      degree of consensus between experts and alumni suggests that these public health
      competencies and impact variables can be used to design and evaluate MPH
      programmes, as well as for individual and team assessment and continuous
      professional development in LMICs.

PMID- 24438673
TI  - Vaccine-preventable diseases: the role of the European Centre for Disease
      Prevention and Control.
AB  - The role of the European Centre for Disease Prevention and Control (ECDC) is to
      strengthen the capacity of the European Union (EU) Member States to protect human
      health through the prevention and control of infectious diseases. The main
      objective of the programme on vaccine-preventable diseases and invasive bacterial
      infections (VPD) is to provide robust evidence and high-quality technical support
      to the EU Member States to help them in their efforts to prevent and control VPD.
      Since the establishment of ECDC, several existing VPD surveillance networks have
      been transferred to ECDC, namely EU-IBIS, DIPNET and EUVAC. In addition to
      surveillance of diseases, ECDC is collecting information and monitoring other
      parameters that are of crucial importance for a well-functioning immunization
      system, including vaccination coverage. The VPD programme also provides
      independent scientific opinions in the area of immunization and initiates and
      coordinates scientific studies in the area of vaccination to answer specific
      questions of public health importance, including risk perception and analysis of
      behaviour in different population groups. One of the overall ECDC priorities over
      recent years is the Centre's involvement in measles elimination. The 'Message'
      tool and the 'Measles Atlas' are examples of work aiming at supporting the
      efforts of Member States in the elimination phase. 

PMID- 24438674
TI  - Massive deregulation of miRNAs from nuclear reprogramming errors during
      trophoblast differentiation for placentogenesis in cloned pregnancy.
AB  - BACKGROUND: Low efficiency of Somatic Cell Nuclear Transfer (NT) has been widely
      addressed with high incidence of placental abnormalities due to genetic and
      epigenetic modifications. MiRNAs are shown to be major regulators of such
      modifications. The present study has been carried out to identify the expression
      patterns of 377 miRNAs, their functional associations and mechanism of regulation
      in bovine placentas derived from artificial insemination (AI), in vitro
      production (IVP) and NT pregnancies. RESULTS: This study reveals a massive
      deregulation of miRNAs as chromosomal cluster or miRNA families without sex
      linkage in NT and in-vitro derived IVP placentas. Cell specific localization
      miRNAs in blastocysts and expression profiling of embryos and placentas at
      different developmental stages identified that the major deregulation of miRNAs
      exhibited in placentas at day 50 of pregnancies is found to be less dependent on
      global DNA methylation, rather than on aberrant miRNA biogenesis molecules. Among
      them, aberrant AGO2 expression due to hypermethylation of its promoter was
      evident. Along with other factors, aberrant AGO2 expression was observed to be
      associated with multiple defects in trophoblast differentiation through
      deregulation of miRNAs mediated mechanisms. CONCLUSION: These aberrant miRNA
      activities might be associated with genetic and epigenetic modifications in
      abnormal placentogenesis due to maldifferentiation of early trophoblast cell
      lineage in NT and IVP pregnancies. This study provides the first insight into
      genome wide miRNA expression, their role in regulation of trophoblast
      differentiation as well as abnormal placental development in Somatic Cell Nuclear
      Transfer pregnancies to pave the way to improve the efficiency of cloning by
      nuclear transfer.

PMID- 24438675
TI  - Spatial distribution of the sibling species of Anopheles gambiae sensu lato
      (Diptera: Culicidae) and malaria prevalence in Bayelsa State, Nigeria.
AB  - BACKGROUND: Much of the confusing ecophenotypic plasticity of Anopheles gambiae
      sensu lato is attributable to the differential biological traits of the sibling
      species, with their heterogeneous geographical distribution, behavioral
      dissimilarities and divergent population dynamics. These differences are critical
      to their roles in malaria transmission. Studies were, therefore, undertaken on
      the spatial distribution of these species and malaria prevalence rates in Bayelsa
      State, September, 2008-August 2010. METHODS: Mosquito sampling was in 7
      towns/villages in 7 Local Government Areas (LGAs) in 3 eco-vegetational zones:
      Fresh Water Swamp Forest (FWSF): Sagbama, Yenagoa, Kolokuma-Opokuma LGAs;
      Brackish Water Swamp Forest (BWSF): Ogbia, Ekeremor, Southern Ijaw LGAs; Mangrove
      Water Forest (MWF): Nembe LGA. Adults were collected twice quarterly by the
      Pyrethrum Spray Catch (PSC) technique. Anopheles was separated morphologically
      and the sibling species PCR- identified. Simultaneously, malaria prevalence rates
      were calculated from data obtained by the examination of blood smears from
      consenting individuals at hospitals/clinics. RESULTS: An. gambiae s.s. was
      dominant across the 3-eco-vegetational zones. Spatial distribution analyses by
      cell count and nearest neighbor techniques indicated a tendency to clustering of
      species. An. gambiae s.s. and An. arabiensis clustered in Ekeremor LGA while
      these 2 species and An. melas aggregated in Nembe. The gonotrophic
      (physiological) status examination revealed that 34.3, 23.5, 23.1 and 18.4% of
      the population were fed, unfed, gravid and half gravid respectively. The highest
      malaria prevalence rates were obtained at Kolokuma-Opokuma and Nembe LGAs.
      Variation in prevalence rates among LGAs was significant (t = 5.976, df = 6, p
      value = 0.002, p < 0.05). The highest prevalence rate was in the age group, 30-39
      yrs, while the lowest prevalence was in the 0-9 yrs group. CONCLUSION: High
      malaria prevalence rates were associated with An. gambiae s.s. either in
      allopatry or sympatry across eco-vegetational zones. In areas where the sibling
      species clustered, they probably formed nidi for transmission. Socio-economic
      conditions might have contributed to reduced prevalence in Yenagoa, State
      Capital.

PMID- 24438676
TI  - Pathways to palliative care for patients with chronic kidney disease.
AB  - BACKGROUND: Despite the terminal nature of chronic kidney disease (CKD), end-of
      life care planning is often inconsistent and pathways to palliative care are
      unclear. Health professionals' perceptions of palliative care and the prevailing
      context may influence their end-of-life decision making. OBJECTIVES: To identify
      predictors of conservative treatment decisions and their associations with
      referral to palliative care, and to determine the perceptions that health
      professionals have about the role of palliative care in management of CKD.
      METHODS: A retrospective audit of deceased patients' charts, spanning three
      years, and a survey of renal healthcare professionals, documenting CKD palliative
      care practices, knowledge and attitudes was carried out. Records of all patients
      with CKD dying between 1 January 2006 and 31 December 2008 in Australian regional
      renal service were audited. Renal staff from the service were surveyed. Logistic
      regression for binomial outcomes and ordinal logistic regression when more than
      two outcome levels were involved; and thematic analysis using a continual cross
      comparative approach was undertaken. RESULTS: Loss of function, particularly from
      stroke, and severe pain are interpreted as representing levels of suffering which
      would justify the need to withdraw from renal replacement therapy. Family and/or
      patient indecision complicates and disrupts end-of-life care planning and can
      establish a cycle of ambiguity. Whilst renal healthcare professionals support
      early discussion of end-of-life care at predialysis education, congruity with the
      patient and family when making the final decision is of great importance.
      CONCLUSION: Healthcare professionals' beliefs, values and knowledge of palliative
      care influence their end-of-life care decisions. The influence of patient, family
      and clinicians involves negotiation and equivocation. Health professionals
      support the early discussion of end-of-life care in CKD at predialysis education
      to enable clearer decision making.

PMID- 24438677
TI  - Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic
      review.
AB  - Occult hepatitis B (OHB) infection has been reported to play an important role in
      the development of hepatocellular carcinoma (HCC). In this systematic review, a
      significantly higher prevalence of OHB was observed in patients with HCC in the
      presence or absence of HCV infection when compared with control populations
      without HCC. Correspondingly, among adequately designed prospective studies, the
      cumulative probability of developing HCC was significantly greater among patients
      with OHB than among HBV DNA-negative patients in the presence or absence of HCV
      infection. Study design, inclusion criteria, treatment options, methodology and
      potential confounding variables were evaluated, and immunopathogenic mechanisms
      that could be involved in OHB as a risk factor in HCC were reviewed. From this
      analysis, we conclude that although OHB is an independent risk factor in HCC
      development in anti-HCV-negative patients, a synergistic or additive role in the
      occurrence of HCC in HCV-coinfected patients is more problematic due to the HCC
      risk attributable to HCV alone, especially in patients with advanced fibrosis and
      cirrhosis. 

PMID- 24438678
TI  - Relationship between polymorphisms near the IL28B gene and spontaneous HBsAg
      seroclearance: a systematic review and meta-analysis.
AB  - Polymorphisms near the interleukin (IL) 28B gene have been proposed to be
      associated with spontaneous clearance of the hepatitis C virus. The purpose of
      this study was to assess the relationship between IL28B polymorphisms and the
      rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of
      meta-analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant
      studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together
      to assess the strength of the association. Subgroup analyses were mainly
      performed according to ethnicity. A total of 4028 cases with persistent chronic
      hepatitis B and 2327 spontaneously recovered controls were included from 11
      studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant
      association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84-1.14 in the
      dominant model; OR = 1.00, 95% CI: 0.68-1.46 in the recessive model; and OR =
      0.95, 95% CI: 0.82-1.09 in the allelic model). The SNP, rs12980275, had no
      significant association either (OR = 1.03, 95% CI: 0.84-1.26 in the dominant
      model; OR = 1.17, 95% CI: 0.46-2.96 in the recessive model; and OR = 1.04, 95%
      CI: 0.86-1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95%
      CI: 0.77-1.15 in the dominant model; OR = 0.74, 95% CI: 0.34-1.62 in the
      recessive model; and OR = 0.93, 95% CI: 0.77-1.13 in the allelic model).
      Similarly, the results of subgroup analyses by ethnicity also showed no
      association in either the Asian group or non-Asian group. We concluded that there
      was no significant association between common IL28B polymorphisms and the rate of
      spontaneous HBsAg seroclearance. 

PMID- 24438679
TI  - Impact of the peginterferon-alpha 2a and ribavirin plasma levels on viral
      kinetics and sustained virological response in genotype 1 HCV/HIV-co-infected
      patients with the unfavourable non-CC IL28B genotypes.
AB  - Studies on the association between the peginterferon-alpha and ribavirin levels
      and sustained virological response (SVR) have shown yielded conflicting results,
      but most of them were performed before the influence of IL28B polymorphisms was
      known. Our aim was to assess the effects of peginterferon-alpha 2a and ribavirin
      plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV
      co-infected patients according to IL28B genotype. This was a cohort study of HCV
      1/HIV-co-infected patients who were HCV-treatment naive and for whom the efficacy
      of peginterferon-alpha 2a plus ribavirin was evaluated by per-protocol analysis.
      The peginterferon-alpha 2a and ribavirin levels were measured by ELISA and HPLC
      UV, respectively. The relationships among host and viral factors, the trough
      drugs levels and virological responses were analysed by multivariate regression
      analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%).
      Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related
      neither to peginterferon-alpha 2a nor to ribavirin plasma levels, while higher
      levels of both drugs were the only variables independently associated with SVR in
      individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and
      4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines
      were observed in CT/TT patients when pegIFN-alpha 2a and ribavirin plasma levels
      were greater than 3400 pg/mL and 1.6 MUg/mL, respectively. In contrast to the
      results for CC patients, the results in patients carrying the unfavourable CT/TT
      IL28B genotypes showed that plasma levels of both drugs have significant effects
      on viral kinetics and SVR. 

PMID- 24438680
TI  - IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV
      coinfected patients.
AB  - Hepatitis C virus (HCV) infection is associated with insulin resistance (IR),
      although mechanisms leading to IR in these patients are not completely
      understood. The aim of this study was to evaluate the association of interleukin
      28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR
      among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out
      a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA
      (rs10903035) polymorphisms were genotyped by GoldenGate((r)) assay. IR was
      defined as homeostatic model assessment (HOMA) values >=3.00. Univariate and
      multivariate generalized linear models (GLM) were used to compare HOMA values and
      the percentage of patients with IR according to IL28B and IL28RA genotypes. In
      total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not
      significantly associated with HOMA values and IR. In contrast, rs10903035 AA was
      significantly associated with high HOMA values taking into account all patients
      (P = 0.024), as well as the subgroups of patients with significant fibrosis (P =
      0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA
      was significantly associated with IR (HOMA >=3.00) in all patients (adjusted odds
      ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR =
      2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In
      conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the
      glucose homeostasis because AA genotype increases the likelihood of IR, but this
      association was different depending on hepatic fibrosis and HCV genotype. 

PMID- 24438681
TI  - Uptake of hepatitis C treatment among people who inject drugs attending Needle
      and Syringe Programs in Australia, 1999-2011.
AB  - The majority of new and existing cases of hepatitis C virus (HCV) infection occur
      among people who inject drugs (PWID). Despite safe and efficacious HCV antiviral
      therapy, uptake remains low in this population. This study examined trends in HCV
      treatment uptake among a large national sample of PWID attending Australian
      Needle and Syringe Programs between 1999 and 2011. Annual cross-sectional sero
      surveys conducted among PWID since 1995 involve completion of a self-administered
      questionnaire and provision of a dried blood spot for HCV antibody testing.
      Multivariate logistic regression identified variables independently associated
      with HCV treatment uptake among 9478 participants with both self-reported and
      serologically confirmed prior HCV infection. Between 1999 and 2011, the
      proportion currently receiving treatment increased from 1.1% to 2.1% (P < 0.001),
      while the proportion having ever received treatment increased from 3.4% to 8.6%
      (P < 0.001). Men were significantly more likely than women to have undertaken HCV
      treatment (P = 0.002). Among men, independent predictors of HCV treatment uptake
      were homosexual identity and older age; among women, independent predictors
      included homosexual identity and an incarceration history. Despite increases in
      HCV treatment among Australian PWID between 1999 and 2011, uptake remains low.
      Strategies are required to increase the proportion of PWID assessed and treated
      for HCV infection to address the increasing burden of disease. Specific
      approaches that target women may also be warranted. Continued surveillance of HCV
      treatment uptake among PWID will be important to monitor the roll-out of simple,
      safe and more effective HCV treatments expected to be available in the future. 

PMID- 24438682
TI  - The cost of treatment failure: resource use and costs incurred by hepatitis C
      virus genotype 1-infected patients who do or do not achieve sustained virological
      response to therapy.
AB  - Chronic hepatitis C virus (HCV) infection places a considerable economic burden
      on health services. Cost-effectiveness analyses of antiviral treatment for
      patients with chronic HCV infection are dependent on assumptions about cost
      reductions following sustained virological response (SVR) to therapy. This study
      quantified the medium-term difference in health resource usage and costs
      depending on treatment outcome. Retrospective chart review of patients with HCV
      genotype 1 infection who had received at least 2 months pegylated interferon and
      ribavirin therapy, with known treatment outcome was conducted. Disease status was
      categorized as chronic hepatitis, cirrhosis or decompensated liver disease.
      Health resource use was documented for each patient in each disease state. Unit
      costs were from the NHS 'Payment by Results' database and the British National
      Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean
      follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient
      progressed to a more severe liver disease state. Annual transition rates for non
      SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to
      decompensated liver disease). By extrapolation of modelled data over a 5-year
      post-treatment period, failure of patients with chronic hepatitis to achieve SVR
      was associated with a 13-fold increase (roughly L2300) in costs, whilst for
      patients who were retreated, the increase was 56-fold, equating to more than L10
      000. Achievement of an SVR has significant effects on health service usage and
      costs. This work provides real-life data for future cost-effectiveness analyses
      related to the treatment for chronic HCV infection. 

PMID- 24438683
TI  - An inexpensive and worldwide available digital image analysis technique for
      histological fibrosis quantification in chronic hepatitis C.
AB  - Hepatic fibrosis staging is based on semiquantitative scores. Digital imaging
      analysis (DIA) appears more accurate because fibrosis is quantified in a
      continuous scale. However, high cost, lack of standardization and worldwide
      unavailability restrict its use in clinical practice. We developed an inexpensive
      and widely available DIA technique for fibrosis quantification in hepatitis C,
      and here, we evaluate its reproducibility and correlation with semiquantitative
      scores, and determine the fibrosis percentage associated with septal fibrosis and
      cirrhosis. 282 needle biopsies staged by Ishak and METAVIR scores were included.
      Images of trichrome-stained sections were captured and processed using Adobe((r))
      Photoshop((r)) CS3 and Adobe((r)) Bridge((r)) softwares. The percentage of
      fibrosis (fibrosis index) was determined by the ratio between the fibrosis area
      and the total sample area, expressed in pixels calculated in an automated way. An
      excellent correlation between DIA fibrosis index and Ishak and METAVIR scores was
      observed (Spearman's r = 0.95 and 0.92; P < 0.001, respectively). Excellent intra
      observer reproducibility was observed in a randomly chosen subset of 39 biopsies
      with an intraclass correlation index of 0.99 (95% CI, 0.95-0.99). The best cut
      offs associated with septal fibrosis and cirrhosis were 6% (AUROC 0.97, 95% CI,
      0.95-0.99) and 27% (AUROC 1.0, 95% CI, 0.99-1), respectively. This new DIA
      technique had high correlation with semiquantitative scores in hepatitis C. This
      method is reproducible, inexpensive and available worldwide allowing its use in
      clinical practice. The incorporation of DIA technique provides a more complete
      evaluation of fibrosis adding the quantification to architectural patterns. 

PMID- 24438684
TI  - Canine hepacivirus is not associated with chronic liver disease in dogs.
AB  - Canine hepacivirus (CHV) has recently been identified in liver and respiratory
      tract samples from dogs, and comparative phylogenetic analysis has confirmed it
      to be the closest genetic relative of hepatitis C virus (HCV) described to date.
      CHV offers great potential as a model system for HCV, but only if the underlying
      processes of infection and pathogenesis are similar for both viruses. However, it
      is not yet clear if CHV is hepatotrophic. Canine chronic hepatitis (CH) is a
      common and usually idiopathic disease that shares similar histological features
      to that of HCV infection of humans. To date, no study has attempted to determine
      whether CHV is involved in the aetiology of liver disease in dogs. We employed
      two nested PCR assays, using primers targeting regions of the helicase domain of
      CHV NS3, to identify viral nucleic acids in liver samples from 100 dogs with CH
      of unknown cause in the UK. We also used a sensitive luciferase
      immunoprecipitation system (LIPS) assay to screen serum samples from these dogs
      for the presence of anti-CHV antibodies. Surprisingly, there was no evidence of
      exposure to, or a carrier state of, CHV in this large cohort, suggesting that the
      virus is not associated with CH in UK dogs. Future work, including transmission
      studies, is required to understand the pathogenesis of CHV in canids before it
      can be proposed as a surrogate model for HCV-induced liver disease in man. 

PMID- 24438685
TI  - A critical role of the small GTPase Rac1 in Akt2-mediated GLUT4 translocation in
      mouse skeletal muscle.
AB  - Insulin promotes glucose uptake in skeletal muscle by inducing the translocation
      of the glucose transporter GLUT4 to the plasma membrane. The serine/threonine
      kinase Akt2 has been implicated as a key regulator of this insulin action.
      However, the mechanisms whereby Akt2 regulates multiple steps of GLUT4
      translocation remain incompletely understood. Recently, the small GTPase Rac1 has
      been identified as a skeletal muscle-specific regulator of insulin-stimulated
      glucose uptake. Here, we show that Rac1 is a critical downstream component of the
      Akt2 pathway in mouse skeletal muscle as well as cultured myocytes. GLUT4
      translocation induced by constitutively activated Akt2 was totally dependent on
      the expression of Rac1 in L6 myocytes. Moreover, we observed the activation of
      Rac1 when constitutively activated Akt2 was ectopically expressed. Constitutively
      activated Akt2-triggered Rac1 activation was diminished by knockdown of FLJ00068,
      a guanine nucleotide exchange factor for Rac1. Knockdown of Akt2, on the other
      hand, markedly reduced Rac1 activation by a constitutively activated mutant of
      phosphoinositide 3-kinase. In mouse skeletal muscle, constitutively activated
      mutants of Akt2 and phosphoinositide 3-kinase, when ectopically expressed,
      induced GLUT4 translocation. Muscle-specific rac1 knockout markedly diminished
      Akt2- or phosphoinositide 3-kinase-induced GLUT4 translocation, highlighting a
      crucial role of Rac1 downstream of Akt2. Taken together, these results strongly
      suggest a novel regulatory link between Akt2 and Rac1 in insulin-dependent signal
      transduction leading to glucose uptake in skeletal muscle.

PMID- 24438689
TI  - Comparing potentially avoidable hospitalization rates related to ambulatory care
      sensitive conditions in Switzerland: the need to refine the definition of health
      conditions and to adjust for population health status.
AB  - BACKGROUND: Regional rates of hospitalization for ambulatory care sensitive
      conditions (ACSC) are used to compare the availability and quality of ambulatory
      care but the risk adjustment for population health status is often minimal. The
      objectives of the study was to examine the impact of more extensive risk
      adjustment on regional comparisons and to investigate the relationship between
      various area-level factors and the properly adjusted rates. METHODS: Our study is
      an observational study based on routine data of 2 million anonymous insured in 26
      Swiss cantons followed over one or two years. A binomial negative regression was
      modeled with increasingly detailed information on health status (age and gender
      only, inpatient diagnoses, outpatient conditions inferred from dispensed drugs
      and frequency of physician visits). Hospitalizations for ACSC were identified
      from principal diagnoses detecting 19 conditions, with an updated list of ICD-10
      diagnostic codes. Co-morbidities and surgical procedures were used as exclusion
      criteria to improve the specificity of the detection of potentially avoidable
      hospitalizations. The impact of the adjustment approaches was measured by changes
      in the standardized ratios calculated with and without other data besides age and
      gender. RESULTS: 25% of cases identified by inpatient main diagnoses were removed
      by applying exclusion criteria. Cantonal ACSC hospitalizations rates varied from
      to 1.4 to 8.9 per 1,000 insured, per year. Morbidity inferred from diagnoses and
      drugs dramatically increased the predictive performance, the greatest effect
      found for conditions linked to an ACSC. More visits were associated with fewer
      PAH although very high users were at greater risk and subjects who had not
      consulted at negligible risk. By maximizing health status adjustment, two thirds
      of the cantons changed their adjusted ratio by more than 10 percent. Cantonal
      variations remained substantial but unexplained by supply or demand. CONCLUSION:
      Additional adjustment for health status is required when using ACSC to monitor
      ambulatory care. Drug-inferred morbidities are a promising approach.

PMID- 24438690
TI  - Comparison of the inter- and intra-observer repeatability of three gait-scoring
      scales for sows.
AB  - Most gait-scoring scales for pigs have a limited number of categories, supposedly
      to improve repeatability. However, reducing the number of categories could lead
      to loss of information if the observers' discriminative capacities are underused.
      With a recently estimated within-herd prevalence of sow lameness of 8.8% to 16.9%
      in the European Union and the associated losses, the availability of reliable
      tools for the timely detection of initial cases warrants attention. This study
      investigated the intra- and inter-observer repeatability (intra-OR and inter-OR)
      of three gait-scoring scales for sows: a continuous 'tagged' visual analogue
      scale (tVAS, measured in mm), a 5-point and a 2-point ordinal scale (5P and 2P),
      all with the same descriptors. Veterinary medicine students (n=108) were trained
      to use the scales and then asked to score 90 videos (30 per scale) of sows with
      normal and abnormal gait. Thirty-six videos were shown once and 18 were randomly
      shown three times, of which one mirrored horizontally. The students' opinions on
      the scales were also collected. Intra- and inter-OR were higher with the tVAS
      than the 2P scale (inter-OR: 0.73 v. 0.60; P<0.05. Intra-OR: 0.80 v. 0.67;
      P<0.05). Intra-OR was higher with the 5P (0.81) than the 2P scale (0.67; P<0.05).
      For all three scales, repeatabilities were lower (P<0.05) for non-lame sows (gait
      score of ?45 mm on the tVAS) than for sows showing some signs of lameness (gait
      score>45 mm). Video order (first 45 v. last 45 clips), mirroring, users' opinions
      on the scales, and previous declared experience in handling pigs or scoring
      lameness in other species had no effect on repeatabilities. Correlations between
      the students' and experts' scores were high (tVAS=0.92; 5P=0.91; 2P=0.88) but the
      association for the 2P was not linear and the frequency distribution showed lower
      correlations for a group of students. This study confirms recent evidence that it
      is possible to design high-resolution gait-scoring scales that do not reduce
      observer repeatability. Visual gait-scoring scales with fewer than five
      categories are likely to entail loss of information on lameness in individual
      sows.

PMID- 24438691
TI  - Adenoidectomy with or without grommets for children with otitis media: an
      individual patient data meta-analysis.
AB  - BACKGROUND: Otitis media (OM) is a leading cause of medical consultations,
      antibiotic prescription and surgery in children. The surgical procedures offered
      to children with recurrent or persistent OM are insertion of grommets,
      adenoidectomy or a combination of the two. There is clear National Institute for
      Health and Care Excellence guidance for the use of grommets in subgroups of
      children with persistent OM with effusion (OME), but similar guidance is not
      available for adenoidectomy, either in persistent OME or in recurrent acute OM
      (AOM). OBJECTIVES: (1) To develop a model to predict the risk of children
      referred for adenoidectomy having a prolonged duration of their OM. Then, (2a) to
      evaluate the overall effect of adenoidectomy, with or without grommets, on OM
      using individual patient data (IPD) and (2b) to identify those subgroups of
      children who are most likely to benefit from adenoidectomy with or without
      grommets. DATA SOURCES: A number of electronic databases were searched from their
      inception including the Cochrane Ear, Nose and Throat Disorders Group Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed,
      EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      metaRegister of Current Controlled Trials (mRCT), ClinicalTrials.gov,
      International Clinical Trials Registry Platform (ICTRP), ClinicalStudyResults.org
      and Google. REVIEW METHODS: Studies eligible for inclusion in this IPD meta
      analysis were randomised controlled trials (RCTs) in children up to 12 years of
      age diagnosed with recurrent AOM and/or persistent OME in which adenoidectomy
      (with or without grommets) was compared with non-surgical treatment or grommets
      alone. The final selection of eligible studies and the quality assessment were
      carried out according to standard methods and disagreement was resolved by
      discussion. RESULTS: A total of 503 articles were identified of which 10 trials
      were included in the meta-analysis; eight of these were at a low risk of bias and
      two were at moderate risk. The primary outcome was failure at 12 months, defined
      by a set of persisting symptoms and signs. In the prognostic analysis 56% of
      those children referred for adenoidectomy (but randomised to the non-surgical
      group) failed to improve (38% of the children with recurrent AOM and 89% of the
      children with persistent OME). Children who had adenoidectomy had a greater
      chance of clinical improvement. The size of that effect is, in general, small but
      persists for at least 2 years. Two subgroups of children are most likely to
      benefit from adenoidectomy: first, children aged < 2 years with recurrent AOM -
      16% of those who had adenoidectomy failed at 12 months whereas 27% of those who
      did not have adenoidectomy failed [rate difference (RD) 12%, 95% confidence
      interval (Cl) 6% to 18%; number needed to treat (NNT) = 9]; second, children aged
      >= 4 years with persistent OME - 51% of those who had adenoidectomy failed at 12
      months whereas 70% of those who did not have adenoidectomy failed (RD 19%, 95% Cl
      12% to 26%; NNT = 6). No significant benefit of adenoidectomy was found in
      children aged >= 2 years with recurrent AOM and children aged < 4 years with
      persistent OME. LIMITATIONS: The need to use a composite end point and the
      limited number of subgroup variables that could be studied are factors that
      reduce the robustness of these results; however, we do not believe that this
      reduces the validity of the conclusions. CONCLUSIONS: Adenoidectomy is most
      beneficial in children with persistent OME aged >= 4 years. A smaller beneficial
      effect was found in children with recurrent AOM aged < 2 years. Consideration
      must be given to the balance between benefits and harms. Future research is
      required in a number of key areas, including defining the best methods of
      selecting, developing and administering patient-reported outcome measures to
      assess the value of treatments for children with persistent OME and recurrent AOM
      and upper respiratory infections; investigating the clinical effectiveness and
      cost-effectiveness of hearing aids (air or bone conduction) and the use of
      interventions to improve classroom acoustics for children with different degrees
      of persistence and severity of hearing loss associated with OME; and
      investigating why professionals' and parents'/carers' treatment preferences vary
      so much both nationally and internationally. We do not understand why
      adenoidectomy works in different subgroups at different ages, nor its effects in
      special populations, such as children with Down syndrome. We also need further
      research on the impact and optimal management of otitis media in these special
      situations and others, such as in children with a cleft palate or developmental
      problems. STUDY REGISTRATION: The study is registered as PROSPERO CRD42011001549.
      FUNDING: The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 24438692
TI  - Regionally accentuated reversible brain grey matter reduction in ultra marathon
      runners detected by voxel-based morphometry.
AB  - BACKGROUND: During the 4,487 km ultra marathon TransEurope-FootRace 2009
      (TEFR09), runners showed catabolism with considerable reduction of body weight as
      well as reversible brain volume reduction. We hypothesized that ultra marathon
      athletes might have developed changes to grey matter (GM) brain morphology due to
      the burden of extreme physical training. Using voxel-based morphometry (VBM) we
      undertook a cross sectional study and two longitudinal studies. METHODS: Prior to
      the start of the race 13 runners volunteered to participate in this study of
      planned brain scans before, twice during, and 8 months after the race. A group of
      matched controls was recruited for comparison. Twelve runners were able to
      participate in the scan before the start of the race and were taken into account
      for comparison with control persons. Because of drop-outs during the race, VBM
      could be performed in 10 runners covering the first 3 time points, and in 7
      runners who also had the follow-up scan after 8 months. Volumetric 3D datasets
      were acquired using an MPRAGE sequence. A level of p < 0.05, family-wise
      corrected for multiple comparisons was the a priori set statistical threshold to
      infer significant effects from VBM. RESULTS: Baseline comparison of TEFR09
      participants and controls revealed no significant differences regarding GM brain
      volume. During the race however, VBM revealed GM volume decreases in regionally
      distributed brain regions. These included the bilateral posterior temporal and
      occipitoparietal cortices as well as the anterior cingulate and caudate nucleus.
      After eight months, GM normalized. CONCLUSION: Contrary to our hypothesis, we did
      not observe significant differences between TEFR09 athletes and controls at
      baseline. If this missing difference is not due to small sample size, extreme
      physical training obviously does not chronically alter GM.However, during the
      race GM volume decreased in brain regions normally associated with visuospatial
      and language tasks. The reduction of the energy intensive default mode network as
      a means to conserve energy during catabolism is discussed. The changes were
      reversible after 8 months.Despite substantial changes to brain composition during
      the catabolic stress of an ultra marathon, the observed differences seem to be
      reversible and adaptive.

PMID- 24438694
TI  - Preliminary performance of cochlear implants in post-lingual patients with
      auditory neuropathy.
AB  - CONCLUSIONS: Auditory restoration can be obtained by using cochlear implants
      (CIs) in post-lingual patients with auditory neuropathy (AN). However,
      improvements in postoperative speech recognition for these patients varied.
      OBJECTIVES: The primary purpose of this study was to assess the postoperative
      performances of two post-lingual AN patients after receiving CIs. METHODS: Two
      post-lingual AN patients received unilateral CIs and the efficacy of the implants
      was then evaluated. One patient was female with bilateral mid-severe hearing loss
      and received an implant at age 28 years. The second patient was male with severe
      hearing loss and he received an implant at age 15 years. The postoperative
      performance for both patients was evaluated. RESULTS: After using the CI for 6
      months, the hearing ability of both subjects was improved by the CI with an
      average post-implant threshold of 35 dB and 44 dB, respectively. The woman made
      significant progress in speech recognition with an open-set spondee recognition
      score of 55% and sentence recognition in quiet score of 90%. Sentence recognition
      in noise scores were 94% (SNR = +10 dB), 88% (SNR = +5 dB), and 80% (SNR = 0 dB).
      The boy achieved improved recognition scores for monosyllables (40%) and
      disyllables (26%), but poor sentence recognition both in quiet (0%) and in noise
      (0%).

PMID- 24438693
TI  - Factors associated with small size at birth in Nepal: further analysis of Nepal
      Demographic and Health Survey 2011.
AB  - BACKGROUND: The global Low Birth Weight (LBW) rate is reported to be 15.5% with
      more than 95% of these LBW infants being from developing countries. LBW is a
      major factor associated with neonatal deaths in developing countries. The
      determinants of low birth weight in Nepal have rarely been studied. This study
      aimed to identify the factors associated with small size at birth among under
      five children. METHODS: Data from the 2011 Nepal Demographic and Health Survey
      (NDHS) were used. The association between small size at birth and explanatory
      variables were analysed using Chi-square tests (chi2) followed by logistic
      regression. Complex Sample Analysis was used to adjust for study design and
      sampling. RESULTS: A total of 5240 mother- singleton under five child pairs were
      included in the analysis, of which 936 (16.0%) children were reported as small
      size at birth. Of 1922 infants whose birth weight was recorded, 235 (11.5%)
      infants had low birth weight (<2500 grams). The mean birth weight was 3030 grams
      (standard deviation: 648.249 grams).The mothers who had no antenatal visits were
      more likely (odds ratio (OR) 1.315; 95% confidence interval (CI) (1.042-1.661))
      to have small size infants than those who had attended four or more antenatal
      visits. Mothers who lived in the Far-western development region were more likely
      to have (OR 1.698; 95% CI (1.228-2.349)) small size infants as compared to
      mothers from the Eastern development region. Female infants were more likely (OR
      1.530; 95% CI (1.245-1.880)) to be at risk of being small than males. CONCLUSION:
      One in every six infants was reported to be small at birth. Attendance of
      antenatal care programs appeared to have a significant impact on birth size.
      Adequate antenatal care visits combined with counselling and nutritional
      supplementation should be a focus to reduce adverse birth outcomes such as small
      size at birth, especially in the geographically and economically disadvantaged
      areas such as Far-western region of Nepal.

PMID- 24438695
TI  - Concurrent three-dimensional conformal radiotherapy and chemotherapy for
      postoperative recurrence of mediastinal lymph node metastases in patients with
      esophageal squamous cell carcinoma: a phase 2 single-institution study.
AB  - AIM: The aim of this study was to evaluate the effects of radiotherapy plus
      concurrent weekly cisplatin chemotherapy on the postoperative recurrence of
      mediastinal lymph node metastases in esophageal cancer patients. METHODS: Ninety
      eight patients were randomly enrolled to receive either three-dimensional
      conformal radiotherapy alone (group A) or concurrent chemoradiotherapy (group B).
      A radiation dose of 62-70 Gy/31-35 fractions was delivered to the recurrent
      tumor. Furthermore, the patients in group B simultaneously received weekly doses
      of cisplatin (30 mg/m(2)), and the survival outcomes and toxic effects were
      compared. RESULTS: The response rate of group B (91.8%) was significantly greater
      than that of group A (73.5%) (chi(2) = 5.765, P = 0.016). The 1- and 3-year
      survival rates of group B (85.7% and 46.9%, respectively) were also greater than
      those of group A (69.4% and 28.6%, respectively). However, there were no
      significant differences in the 5-year survival rates. The numbers of patients who
      died of distant metastases in groups A and B were 13 (26.5%) and 5 (10.2%),
      respectively (chi(2) = 4.356, P = 0.036). Acute radiation-related esophagitis and
      granulocytopenia in group B was frequent. However, intergroup differences in
      terms of late toxicity were not significant. CONCLUSIONS: Three-dimensional
      conformal radiotherapy (3DCRT) is a practical and feasible technique to treat the
      recurrence of mediastinal lymph node metastases of postoperative esophageal
      cancer. In addition, concurrent chemotherapy can increase local tumor control,
      decrease the distant metastasis rate, and increase the long-term survival rate.

PMID- 24438697
TI  - Towards an advanced therapy medicinal product based on mesenchymal stromal cells
      isolated from the umbilical cord tissue: quality and safety data.
AB  - INTRODUCTION: Standardization of mesenchymal stromal cells (MSCs) manufacturing
      is urgently needed to enable translational activities and ultimately facilitate
      comparison of clinical trial results. In this work we describe the adaptation of
      a proprietary method for isolation of a specific umbilical cord tissue-derived
      population of MSCs, herein designated by its registered trademark as UCX(r),
      towards the production of an advanced therapy medicinal product (ATMP). METHODS:
      The adaptation focused on different stages of production, from cell isolation
      steps to cell culturing and cryopreservation. The origin and quality of materials
      and reagents were considered and steps for avoiding microbiological and endotoxin
      contamination of the final cell product were implemented. Cell isolation
      efficiency, MSCs surface markers and genetic profiles, originating from the use
      of different medium supplements, were compared. The ATMP-compliant UCX(r) product
      was also cryopreserved avoiding the use of dimethyl sulfoxide, an added benefit
      for the use of these cells as an ATMP. Cells were analyzed for expansion capacity
      and longevity. The final cell product was further characterized by flow
      cytometry, differentiation potential, and tested for contaminants at various
      passages. Finally, genetic stability and immune properties were also analyzed.
      RESULTS: The isolation efficiency of UCX(r) was not affected by the introduction
      of clinical grade enzymes. Furthermore, isolation efficiencies and phenotype
      analyses revealed advantages in the use of human serum in cell culture as opposed
      to human platelet lysate. Initial decontamination of the tissue followed by the
      use of mycoplasma- and endotoxin-free materials and reagents in cell isolation
      and subsequent culture, enabled the removal of antibiotics during cell expansion.
      UCX(r)-ATMP maintained a significant expansion potential of 2.5 population
      doublings per week up to passage 15 (P15). They were also efficiently
      cryopreserved in a DMSO-free cryoprotectant medium with approximately 100%
      recovery and 98% viability post-thaw. Additionally, UCX(r)-ATMP were genetically
      stable upon expansion (up to P15) and maintained their immunomodulatory
      properties. CONCLUSIONS: We have successfully adapted a method to consistently
      isolate, expand and cryopreserve a well-characterized population of human
      umbilical cord tissue-derived MSCs (UCX(r)), in order to obtain a cell product
      that is compliant with cell therapy. Here, we present quality and safety data
      that support the use of the UCX(r) as an ATMP, according to existing
      international guidelines.

PMID- 24438698
TI  - Feeding behaviour of Culicoides spp. (Diptera: Ceratopogonidae) on cattle and
      sheep in northeast Germany.
AB  - BACKGROUND: Culicoides spp. play an important role in the transmission of several
      vector-borne pathogens such as Bluetongue and Schmallenberg virus in Europe. To
      better understand the biology of local Culicoides species, a study divided into
      three parts was performed in northeast Germany to elucidate the feeding activity
      patterns (study A), preferential landing and feeding sites (study B) and host
      feeding preferences (study C) of Culicoides spp. using cattle and sheep as baits.
      METHODS: In study A, the activity of Culicoides spp. was monitored over a 72 h
      period by collecting insects at regular intervals from the interior of drop traps
      with cattle or sheep standing inside. In study B, Culicoides spp. were directly
      aspirated from the coat and fleece of cattle and sheep during the peak activity
      period of Culicoides. In study C, Culicoides spp. were collected using drop traps
      with either cattle or sheep standing inside and located 10 m apart. RESULTS: In
      study A, 3,545 Culicoides midges belonging to 13 species were collected, peak
      activity was observed at sunset. In study B, 2,024 Culicoides midges were
      collected. A significantly higher number of midges was collected from the belly
      and flank of cattle in comparison to their head region. In study C, 3,710
      Culicoides midges were collected; 3,077 (83%) originated from cattle and 633
      (17%) from sheep. Nearly half (46.7%) of the midges collected from cattle were
      engorged, significantly more than the number of engorged midges collected from
      sheep (7.5%). Culicoides from the Obsoletus complex (C. obsoletus and C.
      scoticus) were the most common Culicoides species encountered, followed by C.
      punctatus. Other species identified were C. dewulfi, C. chiopterus, C. pulicaris,
      C. lupicaris, C. pallidicornis, C. subfascipennis, C. achrayi, C. stigma, C.
      griseidorsum and C. subfagineus, the last two species are reported for the first
      time in Germany. Engorged C. chiopterus were collected in relatively high numbers
      from sheep, suggesting that this species may have a preference for sheep.
      CONCLUSIONS: An insight into the feeding behaviour of local Culicoides species
      under field conditions in northeast Germany was obtained, with implications for
      the implementation of control measures and midge-borne disease risk analysis.

PMID- 24438699
TI  - A clinical review of maternal bacteremia.
AB  - OBJECTIVE: To carry out a 4-year review of cases of bacteremia among obstetric
      patients. METHODS: In a retrospective review, all cases of maternal bacteremia
      between 2009 and 2012 were identified from the laboratory database of Coombe
      Women and Infants University Hospital, Dublin, Ireland. The clinical records of
      each case were assessed. RESULTS: During the study period, 37,584 obstetric
      patients attended the hospital. There were 58 cases of bacteremia: 19 were
      diagnosed prepartum, 20 intrapartum, and 19 postpartum. There were no maternal
      deaths. Two cases resulted in septic shock. Four cases were associated with early
      pregnancy loss, and 2 with stillbirth. Fifty-four cases occurred among 34,956
      women who delivered a neonate weighing 500 g or more (0.15%). Escherichia coli
      most frequently caused prepartum and postpartum bacteremia, whereas Streptococcus
      agalactiae (beta-hemolytic, Lancefield group B) most frequently caused
      intrapartum bacteremia. There was no association between the development of
      bacteremia and maternal risk factors including employment status, obesity,
      parity, smoking status, and maternal age. Most organisms cultured were sensitive
      to first-line antibiotics; there were no cases of bacteremia caused by multi-drug
      resistant organisms. CONCLUSION: The incidence of maternal bacteremia in the
      study population was low and was usually associated with good maternal and fetal
      outcomes.

PMID- 24438707
TI  - T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report.
AB  - A girl was diagnosed with cystic fibrosis (CF) at birth, with repeatedly positive
      sweat tests and homozygous F508del mutations of her CF transmembrane conductance
      regulator (CFTR) gene. From an early age, her lung disease was more severe than
      her birth cohort peers despite aggressive treatment. At the age of 16 she was
      listed for lung transplantation, but prior to transplant was not on systemic
      corticosteroids or other immunosuppressive agents. In response to ex vivo
      stimulation, her pre-transplant peripheral blood T cells unexpectedly failed to
      produce detectable levels of IFN-gamma, unlike cells from healthy controls or
      from another girl with CF and lung disease of comparable severity. Furthermore,
      naive T cells freshly isolated from her peripheral blood showed a complete block
      of T cell differentiation into Th1, Th17 and Treg lineages, even in the presence
      of cytokines known to promote differentiation into the respective lineages. Her
      serology has been remarkably devoid of evidence of exposure to viruses that have
      been associated with T cell exhaustion. However, her freshly isolated naive T
      cells showed sustained expression of markers of T cell exhaustion, which were
      further induced upon ex vivo stimulation, pointing to T cell exhaustion as the
      cause of the failure of naive T cells to undergo differentiation in response to
      cytokine stimulation. Although excessive inflammation in CF lung can be both
      ineffective at clearing certain pathogens as well as destructive to the lung
      tissue itself, adequate inflammation is a component of an effective overall
      immune response to microbial pathogens. Our present findings suggest that
      intrinsic impairment of T cell differentiation may have contributed to the
      greater severity and more rapid progression of her CF lung disease than of the
      lung disease of most of her peers. 

PMID- 24438709
TI  - Combating medical device fouling.
AB  - When interfaced with the biological environment, biomedical devices are prone to
      surface biofouling due to adhesion of microbial or thrombotic agents as a result
      of the foreign body response. Surface biofouling of medical devices occurs as a
      result of nonspecific adhesion of noxious substrates to the surface. Approaches
      for biofouling-resistant surfaces can be categorized as either the manipulation
      of surface chemical functionalities or through the incorporation of regulatory
      biomolecules. This review summarizes current strategies for creating biofouling
      resistant surfaces based on surface hydrophilicity and charge, biomolecule
      functionalization, and drug elution. Reducing the foreign body response and
      restoring the function of cells around the device minimizes the risk of device
      rejection and potentially integrates devices with surrounding tissues and fluids.
      In addition, we discuss the use of peptides and NO as biomolecules that not only
      inhibit surface fouling, but also promote the integration of medical devices with
      the biological environment. 

PMID- 24438710
TI  - Review: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task
      Force.

PMID- 24438711
TI  - Improving the usefulness of budget impact analyses: a U.S. payer perspective.

PMID- 24438712
TI  - Budget impact analysis-principles of good practice: report of the ISPOR 2012
      Budget Impact Analysis Good Practice II Task Force.
AB  - BACKGROUND: Budget impact analyses (BIAs) are an essential part of a
      comprehensive economic assessment of a health care intervention and are
      increasingly required by reimbursement authorities as part of a listing or
      reimbursement submission. OBJECTIVES: The objective of this report was to present
      updated guidance on methods for those undertaking such analyses or for those
      reviewing the results of such analyses. This update was needed, in part, because
      of developments in BIA methods as well as a growing interest, particularly in
      emerging markets, in matters related to affordability and population health
      impacts of health care interventions. METHODS: The Task Force was approved by the
      International Society for Pharmacoeconomics and Outcomes Research Health Sciences
      Policy Council and appointed by its Board of Directors. Members were experienced
      developers or users of BIAs; worked in academia and industry and as advisors to
      governments; and came from several countries in North America and South America,
      Oceania, Asia, and Europe. The Task Force solicited comments on the drafts from a
      core group of external reviewers and, more broadly, from the membership of the
      International Society for Pharmacoeconomics and Outcomes Research. RESULTS: The
      Task Force recommends that the design of a BIA for a new health care intervention
      should take into account relevant features of the health care system, possible
      access restrictions, the anticipated uptake of the new intervention, and the use
      and effects of the current and new interventions. The key elements of a BIA
      include estimating the size of the eligible population, the current mix of
      treatments and the expected mix after the introduction of the new intervention,
      the cost of the treatment mixes, and any changes expected in condition-related
      costs. Where possible, the BIA calculations should be performed by using a simple
      cost calculator approach because of its ease of use for budget holders. In
      instances, however, in which the changes in eligible population size, disease
      severity mix, or treatment patterns cannot be credibly captured by using the cost
      calculator approach, a cohort or patient-level condition-specific model may be
      used to estimate the budget impact of the new intervention, accounting
      appropriately for those entering and leaving the eligible population over time.
      In either case, the BIA should use data that reflect values specific to a
      particular decision maker's population. Sensitivity analysis should be of
      alternative scenarios chosen from the perspective of the decision maker. The
      validation of the model should include at least face validity with decision
      makers and verification of the calculations. Data sources for the BIA should
      include published clinical trial estimates and comparator studies for the
      efficacy and safety of the current and new interventions as well as the decision
      maker's own population for the other parameter estimates, where possible. Other
      data sources include the use of published data, well-recognized local or national
      statistical information, and, in special circumstances, expert opinion. Reporting
      of the BIA should provide detailed information about the input parameter values
      and calculations at a level of detail that would allow another modeler to
      replicate the analysis. The outcomes of the BIA should be presented in the format
      of interest to health care decision makers. In a computer program, options should
      be provided for different categories of costs to be included or excluded from the
      analysis. CONCLUSIONS: We recommend a framework for the BIA, provide guidance on
      the acquisition and use of data, and offer a common reporting format that will
      promote standardization and transparency. Adherence to these good research
      practice principles would not necessarily supersede jurisdiction-specific BIA
      guidelines but may support and enhance local recommendations or serve as a
      starting point for payers wishing to promulgate methodology guidelines.

PMID- 24438713
TI  - The effect of supplemental medical and prescription drug coverage on health care
      spending for Medicare beneficiaries with cancer.
AB  - OBJECTIVES: To examine whether patients with newly diagnosed cancer respond
      differently to supplemental coverage than the general Medicare population.
      METHODS: A cohort of newly diagnosed cancer patients (n = 1,799) from the 1997
      2007 Medicare Current Beneficiary Survey and a noncancer cohort (n = 9,726) were
      identified and matched by panel year. Two-year total medical care spending was
      estimated by using generalized linear models with gamma distribution and log link
      including endogeneity-corrected models. Interactions between cancer and type of
      insurance allowed testing for differential effects of a cancer diagnosis.
      RESULTS: The cancer cohort spent an adjusted $15,605 more over 2 years than did
      the noncancer comparison group. Relative to those without supplemental coverage,
      beneficiaries with employer-sponsored insurance, other private with prescription
      drug coverage, and public coverage had significantly higher total spending
      ($3,510, $2,823, and $4,065, respectively, for main models). For beneficiaries
      with cancer, supplemental insurance effects were similar in magnitude yet
      negative, suggesting little net effect of supplemental insurance for cancer
      patients. The endogeneity-corrected models produced implausibly large main
      effects of supplemental insurance, but the Cancer * Insurance interactions were
      similar in both models. CONCLUSIONS: Medicare beneficiaries with cancer are less
      responsive to the presence and type of supplemental insurance than are
      beneficiaries without cancer. Proposed restrictions on the availability of
      supplemental insurance intended to reduce Medicare spending would be unlikely to
      limit expenditures by beneficiaries with cancer, but would shift the financial
      burden to those beneficiaries. Policymakers should consider welfare effects
      associated with coverage restrictions.

PMID- 24438714
TI  - The cost-effectiveness of a pharmacogenetic test: a trial-based evaluation of
      TPMT genotyping for azathioprine.
AB  - BACKGROUND: Thiopurine-methyl transferase (TPMT) testing prior to the
      prescription of azathioprine in autoimmune diseases is one of the few examples of
      a pharmacogenetic test that has made the transition from research into clinical
      practice. TPMT testing could lead to improved prescribing of azathioprine
      resulting in a reduction in adverse drug reactions as well as an improvement in
      effectiveness. When allocating scarce resources robust evidence on cost
      effectiveness is required. OBJECTIVE: This study aimed to evaluate the cost
      effectiveness of a TPMT genotyping test to inform azathioprine prescribing in
      autoimmune diseases. The secondary aim of this study was to demonstrate the
      complexity of undertaking a trial-based evaluation of a pharmacogenetic test.
      METHODS: A prospective economic evaluation was conducted alongside the TARGET
      (TPMT: Azathioprine Response to Genotype and Enzyme Testing) study, a pragmatic
      controlled trial that randomized (1:1) patients to undergo TPMT genotyping before
      azathioprine (n = 167) or current practice (n = 166). Assuming the UK health
      service perspective and a time horizon of 4 months, resource-use and health
      status data were collected prospectively for all recruited patients. RESULTS: The
      mean incremental cost for TPMT genotyping and subsequent care pathways compared
      with current practice for the 4-month follow-up was -L421.06 (95% confidence
      interval -L925.15 to L89.75). Mean incremental quality-adjusted life-years were
      close to zero but negative: -0.008 (95% confidence interval -0.017 to 0.0002).
      Assuming a threshold of L20,000 per quality-adjusted life-year, the expected
      incremental net benefit of introducing the test is L256.89 (95% CI -L425.94 to
      L932.86). CONCLUSIONS: TPMT genotyping potentially offers a less expensive
      alternative than current practice, but it may also have a small but negative
      effect on health status. These findings are associated with significant
      uncertainty, and the causal effect of TPMT genotyping on changes in health status
      and health care resource use remains uncertain. The results from this study
      therefore pose a difficult challenge to decision makers.

PMID- 24438715
TI  - Cost-utility analysis of platinum-based chemotherapy versus taxane and other
      regimens for ovarian cancer.
AB  - OBJECTIVES: Most economic evaluations of chemotherapies for ovarian cancer
      patients have used hypothetical cohorts or randomized control trials, but
      evidence integrating real-world survival, cost, and utility data is limited.
      METHODS: A propensity score-matched cohort of 6856 elderly (>=65 years) ovarian
      cancer patients diagnosed from 1991 to 2005 from the Surveillance, Epidemiology,
      and End Results-Medicare data cohort were included. Treatment regimens (i.e., no
      chemotherapy, platinum-based only, platinum plus taxane, and other nonplatinum)
      were identified in the 6 months postdiagnosis. Patients were followed until death
      or end of study (December 2006). Effectiveness was measured in quality-adjusted
      life-years (QALYs), and total health care costs were measured by using a payer's
      perspective (2009 US dollars). Methodological and statistical uncertainties were
      accounted by including alternative scenarios (for utility values) and net
      monetary benefit approach. Incremental cost-effectiveness ratios (ICERs) were
      calculated, and stratified analyses were performed by tumor stages and age
      groups. RESULTS: On comparing the platinum-based group versus no chemotherapy, we
      found that the ICER was $30,073/QALY and $58,151/QALY for early- and late-stage
      disease, respectively, while other nonplatinum and platinum plus taxane groups
      were dominated (less effective and more costly). Similar results were found
      across alternative scenarios and age groups. For patients 85 years or older,
      platinum plus taxane, however, was not dominated by the platinum-based group,
      with an ICER of $133,892/QALY. CONCLUSIONS: Following elderly ovarian cancer
      patients over a lifetime using real-world longitudinal data and adjusting for
      quality of life, we found that treatment with platinum-based regimen was the most
      cost-effective treatment alternative.

PMID- 24438716
TI  - Impact of osteoporosis on high-cost chronic diseases.
AB  - OBJECTIVE: To assess the impact of osteoporosis on health care costs for patients
      with chronic disease (CD): cardiovascular disease (CVD), chronic obstructive
      pulmonary disease (COPD), depression, diabetes mellitus (DM), or two or more of
      these CDs. METHODS: This retrospective analysis included commercially insured or
      Medicare Advantage male and female members aged 50 years or older with medical
      and pharmacy benefits who had evidence of osteoporosis and/or one of the CDs
      during the identification period (January 1, 2007, to October 31, 2009). Cohorts
      were defined by the presence or absence of osteoporosis and CD (osteoporosis
      ONLY, CD ONLY, and CD plus osteoporosis) and, for osteoporosis cohorts, by
      incident (recent diagnosis) or prevalent osteoporosis (long-standing). Primary
      outcome was total health care costs during 1-year follow-up. Costs, adjusted for
      baseline characteristics, were analyzed with a generalized linear model with log
      link and gamma distribution. RESULTS: Of the 494,160 patients, the majority had
      evidence of CD with or without osteoporosis: CVD (54%), two or more CDs (24%), DM
      (8%), depression (4%), COPD (1%); 9% had osteoporosis ONLY. The range of actual
      mean costs was as follows: CD ONLY, $8,377 (CVD) to $12,801 (two or more CDs); CD
      plus incident osteoporosis, $15,696 (CVD) to $23,860 (two or more CDs); CD plus
      prevalent osteoporosis, $10,038 (CVD) to $17,997 (two or more CDs). Compared with
      CD ONLY, baseline-adjusted costs were 66% (two or more CDs) to 91% (DM) higher
      for CD plus incident osteoporosis and 13% (CVD) to 23% (depression) higher for CD
      plus prevalent osteoporosis (P < 0.001). CONCLUSIONS: The burden of osteoporosis
      in patients with CD is significant, particularly for patients with newly
      diagnosed osteoporosis.

PMID- 24438717
TI  - Differences in health services utilization and costs between antihypertensive
      medication users versus nonusers in adults with diabetes and concomitant
      hypertension from Medical Expenditure Panel Survey pooled years 2006 to 2009.
AB  - OBJECTIVES: To compare population-level baseline characteristics, individual
      level utilization, and costs between antihypertensive medication users versus
      nonusers in adults with diabetes and concomitant hypertension. METHODS: This
      longitudinal retrospective observational research used Medical Expenditure Panel
      Survey household component pooled years 2006 to 2009 to analyze adults 18 years
      or older with nongestational diabetes and coexistent essential hypertension. Two
      groups were created: 1) antihypertensive medication users and 2) no
      antihypertensive pharmacotherapy. We examined average annualized health care
      costs and emergency department and hospital utilization. Accounting for Medical
      Expenditure Panel Survey's complex survey design, all analyses used longitudinal
      weights. Logistic regressions examined the likelihood of utilization and
      anytihypertensive medication use, and log-transformed multiple linear regression
      models assessed costs and antihypertensive medication use. RESULTS: Of the 3261
      adults identified with diabetes, 66% (n = 2137) had concomitant hypertension
      representing 38.7 million individuals during 2006 to 2009. Significantly, the 16%
      (n = 338) no antihypertensive pharmacotherapy group showed greater mean nights
      hospitalized (3.6 vs. 1.7, P = 0.0120), greater all-cause hospitalization events
      per 1000 patient months (41 vs. 24, P = 0.0.007), and lower mean diabetes-related
      and hypertension-related ambulatory visits. After adjusting for confounders, non
      antihypertensive medication users showed 1.64 odds of hospitalization, 29% lower
      total, and 27% lower average annualized medical expenses compared with
      antihypertensive medication users. CONCLUSIONS: In adults with diabetes and
      coexistent hypertension, we observed significantly greater hospitalizations and
      lower costs for the non antihypertensive pharmacotherapy group versus those using
      antihypertensive medications. The short-term time horizon greater
      hospitalizations with lower expenses among non-antihypertensive medication users
      with diabetes and concomitant hypertension warrant further study.

PMID- 24438718
TI  - Development of a symptom index for patients with primary brain tumors.
AB  - OBJECTIVES: This study's primary goals included identifying the highest priority
      symptoms of patients with advanced brain tumors on treatment, comparing patient
      priority ratings with those of oncology experts, and constructing a brief symptom
      index using combined input to assess these symptoms and concerns. METHODS: Fifty
      patients with advanced primary brain tumors and 10 physician experts were
      recruited from the National Comprehensive Cancer Network institutions and
      community support agencies. By using a 40-item symptom checklist, patients first
      selected up to 10 of the most important symptoms/concerns to monitor when
      assessing the value of drug treatment for brain tumors, then nominated up to 5 of
      the very most important concerns, and finally generated additional
      symptoms/concerns. By using the same checklist as patients, physicians rated each
      symptom/concern as disease- or treatment-related. RESULTS: By using the combined
      input, a 24-item National Comprehensive Cancer Network/Functional Assessment of
      Cancer Therapy-Brain Symptom Index (NFBrSI-24) was developed. The NFBrSI-24
      showed good internal consistency (alpha = 0.84), significantly differentiated
      patients with different levels of functional status (F2,47 = 8.21; P < .001), and
      demonstrated good convergent validity with the Functional Assessment of Cancer
      Therapy-General functional, physical, social, emotional, and brain tumor-specific
      concerns (rho = 0.59, 0.57, 0.40, 0.35, and 0.50, respectively; Ps < 0.05).
      CONCLUSIONS: The NFBrSI-24, an index of the symptoms in advanced brain tumors
      perceived as most important by both patients and clinicians, improves upon
      existing measures of brain tumor symptoms through better satisfaction of
      regulatory requirements for measure development. The findings suggest good
      reliability and validity, indicating that the NFBrSI-24 is a promising brief
      assessment of high-priority advanced brain tumor symptoms for research and
      clinical settings.

PMID- 24438719
TI  - From translation to version management: a history and review of methods for the
      cultural adaptation of the EuroQol five-dimensional questionnaire.
AB  - The EuroQol five-dimensional (EQ-5D) questionnaire is used worldwide as a patient
      reported outcome (PRO) instrument for the measurement and valuation of health.
      Several variants of the instrument now exist, including versions with three and
      five levels of severity and one for respondents aged 8 to 14 years. From the
      outset, a demand for new language versions of the EQ-5D questionnaire meant that
      there was a need to implement standardized procedures, which ensured that such
      versions were produced following international recommendations for the cultural
      adaptation of patient-reported outcomes. The availability of new variants and
      formats of the instrument, such as telephone-administered or electronic formats,
      complicated the task of providing and controlling the quality of cultural
      adaptations. Although cultural adaptations of the instrument are widely used, the
      procedures currently used to produce them have not been widely disseminated. The
      present article therefore describes the evolution of the production of other
      language versions of the instrument from the earliest days of simultaneous
      production and translation of the EQ-5D questionnaire to the more recent, broader
      based strategy of version management. We describe current adaptation procedures
      and innovations within those procedures. We also describe how version management
      is organized within the EuroQol Group, review aspects related to quality control,
      and provide an overview of the number of currently available language versions
      for each variant of the EQ-5D questionnaire: three-level, five-level, and youth
      versions. We conclude by discussing some of the relevant issues related to
      cultural adaptation for frequently used instruments such as the EQ-5D
      questionnaire. 

PMID- 24438720
TI  - Health utility scores in Alzheimer's disease: differences based on calculation
      with American and Canadian preference weights.
AB  - OBJECTIVE: Health utility scores quantify health-related quality-of-life (HRQOL)
      in Alzheimer's disease (AD). These scores are calculated by using preference
      weights derived from general population samples. We recruited persons with AD and
      their primary informal caregivers and examined differences in health utility
      scores calculated by using two sets of published preference weights. METHODS: We
      recruited participants from nine clinics across Canada and administered the
      EuroQol five-dimensional (EQ-5D) questionnaire HRQOL instrument. We converted
      participants' EQ-5D questionnaire responses into two sets of health utility
      scores by using US and Canadian preference weights. We assessed agreement between
      sets by using the intraclass correlation coefficient. Bland-Altman plots depicted
      individual-level differences between sets. RESULTS: For 216 persons with AD and
      their caregivers, mean health utility scores were higher when calculated with US
      instead of Canadian preference weights (P < 0.0001). The intraclass correlation
      coefficient (95% CI) was 0.79 (0.05-0.93) in the persons with AD group and 0.83
      (0.30-0.94) in the caregiver group. Ninety-five percent of the individual
      differences in utility score fell between -0.16 and 0.03 for persons with AD and 
      0.15 and 0.05 for caregivers. Forty-three percent of these differences exceeded a
      minimum clinically important threshold of 0.074. CONCLUSIONS: In AD studies,
      researchers should calculate health utility scores by using preference weights
      obtained in the general population of their country of interest. Using weights
      from other countries' populations could bias the utilities and adversely affect
      the results of economic evaluations of AD treatments.

PMID- 24438721
TI  - EQ-5D versus SF-12 in coronary patients: are they interchangeable?
AB  - OBJECTIVES: The aim of this study was to compare EuroQol five-dimensional (EQ-5D)
      utility scores and six-dimensional health state classification (SF-6D) utility
      scores (derived from the 12-Item Short-Form Health Survey [SF-12]) by using a
      large European sample of patients with stable coronary heart disease. Special
      attention was given to country-specific results. METHODS: Data from the EURopean
      Action on Secondary and Primary Prevention by Intervention to Reduce Events III
      (EUROASPIRE III) survey were used. Patients hospitalized for a coronary artery
      bypass graft, percutaneous coronary intervention, acute myocardial infarction, or
      myocardial ischemia were interviewed and examined at least 6 months after their
      acute event. Health-related quality of life was assessed by using the EQ-5D and
      the SF-12. SF-12 outcomes were converted to SF-6D utility values, allowing
      comparison between both measures. RESULTS: Both EQ-5D and SF-6D results were
      available for 7472 patients with coronary heart disease from 20 European
      countries. The measures were significantly correlated (intraclass correlation
      coefficient = 0.536); however, large differences between the two measures remain.
      A total of 28.8% of the patients reported a ceiling effect on the EQ-5D
      instrument, whereas only 4.2% of the patients reported full health based on the
      SF-6D. Especially the mental component does not seem to be completely captured by
      the EQ-5D instrument. Furthermore, patients with worse EQ-5D outcomes were more
      likely to have better SF-6D results, whereas patients with better EQ-5D outcomes
      were more likely to have worse SF-6D results. CONCLUSIONS: Both measures are not
      interchangeable. Whereas the main disadvantage of the EQ-5D questionnaire is its
      ceiling effect, the potential advantages of SF-12 might disappear when converting
      the outcomes into an SF-6D utility, because of the small differences between
      patients.

PMID- 24438722
TI  - Evaluating direct medical expenditures estimation methods of adults using the
      medical expenditure panel survey: an example focusing on head and neck cancer.
AB  - OBJECTIVE: To inform policymakers of the importance of evaluating various methods
      for estimating the direct medical expenditures for a low-incidence condition,
      head and neck cancer (HNC). METHODS: Four methods of estimation have been
      identified: 1) summing all health care expenditures, 2) estimating disease
      specific expenditures consistent with an attribution approach, 3) estimating
      disease-specific expenditures by matching, and 4) estimating disease-specific
      expenditures by using a regression-based approach. A literature review of studies
      (2005-2012) that used the Medical Expenditure Panel Survey (MEPS) was undertaken
      to establish the most popular expenditure estimation methods. These methods were
      then applied to a sample of 120 respondents with HNC, derived from pooled data
      (2003-2008). RESULTS: The literature review shows that varying expenditure
      estimation methods have been used with MEPS but no study compared and contrasted
      all four methods. Our estimates are reflective of the national treated prevalence
      of HNC. The upper-bound estimate of annual direct medical expenditures of adult
      respondents with HNC between 2003 and 2008 was $3.18 billion (in 2008 dollars).
      Comparable estimates arising from methods focusing on disease-specific and
      incremental expenditures were all lower in magnitude. Attribution yielded annual
      expenditures of $1.41 billion, matching method of $1.56 billion, and regression
      method of $1.09 billion. CONCLUSIONS: This research demonstrates that variation
      exists across and within expenditure estimation methods applied to MEPS data.
      Despite concerns regarding aspects of reliability and consistency, reporting a
      combination of the four methods offers a degree of transparency and validity to
      estimating the likely range of annual direct medical expenditures of a condition.

PMID- 24438723
TI  - A synthesis of drug reimbursement decision-making processes in organisation for
      economic co-operation and development countries.
AB  - BACKGROUND: The use of a restrictive formulary, with placement determined through
      a drug-reimbursement decision-making process, is one approach to managing drug
      expenditures. OBJECTIVE: To describe the processes in drug reimbursement decision
      making systems currently used in national publicly funded outpatient prescription
      drug insurance plans. METHODS: By using the Organisation for Economic Co
      operation and Development (OECD) nations as the sampling frame, a search was done
      in the published literature, followed by the gray literature. Collected data were
      verified by a system expert within the prescription drug insurance plan in each
      country to ensure the accuracy of key data elements across countries. RESULTS:
      All but one country provided at least one publicly funded prescription drug
      formulary. Many systems have adopted similar processes of drug reimbursement
      decision making. All but three systems required additional consideration of
      clinical evidence within the decision-making process. Transparency of
      recommendations varied between systems, from having no information publicly
      available (three systems) to all information available and accessible to the
      public (16 systems). Only four countries did not consider cost within the drug
      reimbursement decision-making process. CONCLUSIONS: There were similarities in
      the decision-making process for drug reimbursement across the systems; however,
      only five countries met the highest standard of transparency, requirement of
      evidence, and ability to appeal. Future work should focus on examining how these
      processes may affect formulary listing decisions for drugs between countries.

PMID- 24438724
TI  - Use of Bayesian multivariate meta-analysis to estimate the HAQ for mapping onto
      the EQ-5D questionnaire in rheumatoid arthritis.
AB  - BACKGROUND: In health technology assessment, decisions about reimbursement for
      new health technologies are largely based on effectiveness estimates. Sometimes,
      however, the target effectiveness estimates are not readily available. This may
      be because many alternative instruments measuring these outcomes are being used
      (and not all always reported) or an extended follow-up time of clinical trials is
      needed to evaluate long-term end points, leading to the limited data on the
      target clinical outcome. In the areas of highest priority in health care,
      decisions are required to be made on a short time scale. Therefore, alternative
      clinical outcomes, including surrogate end points, are increasingly being
      considered for use in evidence synthesis as part of economic evaluation.
      OBJECTIVE: To illustrate the potential effect of reduced uncertainty around the
      clinical outcome on the utility when estimating it from a multivariate meta
      analysis. METHODS: Bayesian multivariate meta-analysis has been used to
      synthesize data on correlated outcomes in rheumatoid arthritis and to incorporate
      external data in the model in the form of informative prior distributions.
      Estimates of Health Assessment Questionnaire were then mapped onto the health
      related quality-of-life measure EuroQol five-dimensional questionnaire, and the
      effect was compared with mapping the Health Assessment Questionnaire obtained
      from the univariate approach. RESULTS: The use of multivariate meta-analysis can
      lead to reduced uncertainty around the effectiveness parameter and ultimately
      uncertainty around the utility. CONCLUSIONS: By allowing all the relevant data to
      be incorporated in estimating clinical effectiveness outcomes, multivariate meta
      analysis can improve the estimation of health utilities estimated through mapping
      methods. While reduced uncertainty may have an effect on decisions based on
      economic evaluation of new health technologies, the use of short-term surrogate
      end points can allow for early decisions. More research is needed to determine
      the circumstances under which uncertainty is reduced.

PMID- 24438725
TI  - Valuing the health states associated with Chlamydia trachomatis infections and
      their sequelae: a systematic review of economic evaluations and primary studies.
AB  - OBJECTIVES: Economic evaluations of interventions to prevent and control sexually
      transmitted infections such as Chlamydia trachomatis are increasingly required to
      present their outcomes in terms of quality-adjusted life-years using preference
      based measurements of relevant health states. The objectives of this study were
      to critically evaluate how published cost-effectiveness studies have
      conceptualized and valued health states associated with chlamydia and to examine
      the primary evidence available to inform health state utility values (HSUVs).
      METHODS: A systematic review was conducted, with searches of six electronic
      databases up to December 2012. Data on study characteristics, methods, and main
      results were extracted by using a standard template. RESULTS: Nineteen economic
      evaluations of relevant interventions were included. Individual studies
      considered different health states and assigned different values and durations.
      Eleven studies cited the same source for HSUVs. Only five primary studies valued
      relevant health states. The methods and viewpoints adopted varied, and different
      values for health states were generated. CONCLUSIONS: Limitations in the
      information available about HSUVs associated with chlamydia and its complications
      have implications for the robustness of economic evaluations in this area. None
      of the primary studies could be used without reservation to inform cost
      effectiveness analyses in the United Kingdom. Future debate should consider
      appropriate methods for valuing health states for infectious diseases, because
      recommended approaches may not be suitable. Unless we adequately tackle the
      challenges associated with measuring and valuing health-related quality of life
      for patients with chlamydia and other infectious diseases, evaluating the cost
      effectiveness of interventions in this area will remain problematic.

PMID- 24438727
TI  - Obesity and prognosis-just one of many cardiovascular paradoxes?

PMID- 24438728
TI  - Overview of epidemiology and contribution of obesity to cardiovascular disease.
AB  - The prevalence of obesity has increased worldwide and is a source of concern
      since the negative consequences of obesity start as early as in childhood. The
      most commonly used anthropometric tool to assess relative weight and classify
      obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped
      association with clinical outcomes and mortality. Such an inverse relationship
      fuels a controversy in the literature, named the 'obesity paradox', which
      associates better survival and fewer cardiovascular (CV) events in patients with
      elevated BMI afflicted with chronic diseases compared to non-obese patients.
      However, BMI cannot make the distinction between an elevated body weight due to
      high levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is
      more frequently associated with metabolic abnormalities than a high level of lean
      body mass. Another explanation for the paradox is the absence of control for
      major individual differences in regional BF distribution. Adipose tissue is now
      considered as a key organ regarding the fate of excess dietary lipids, which may
      determine whether or not body homeostasis will be maintained (metabolically
      healthy obesity) or a state of inflammation/insulin resistance will be produced,
      with deleterious CV consequences. Obesity, particularly visceral obesity, also
      induces a variety of structural adaptations/alterations in CV structure/function.
      Adipose tissue can now be considered as an endocrine organ orchestrating crucial
      interactions with vital organs and tissues such as the brain, the liver, the
      skeletal muscle, the heart and blood vessels themselves. Thus, the evidence
      reviewed in this paper suggests that adipose tissue quality/function is as
      important, if not more so, than its amount in determining the overall health and
      CV risks of overweight/obesity. 

PMID- 24438729
TI  - Fitness vs. fatness on all-cause mortality: a meta-analysis.
AB  - The purpose of this study was to quantify the joint association of
      cardiorespiratory fitness (CRF) and weight status on mortality from all causes
      using meta-analytical methodology. Studies were included if they were (1)
      prospective, (2) objectively measured CRF and body mass index (BMI), and (3)
      jointly assessed CRF and BMI with all-cause mortality. Ten articles were included
      in the final analysis. Pooled hazard ratios were assessed for each comparison
      group (i.e. normal weight-unfit, overweight-unfit and -fit, and obese-unfit and 
      fit) using a random-effects model. Compared to normal weight-fit individuals,
      unfit individuals had twice the risk of mortality regardless of BMI. Overweight
      and obese-fit individuals had similar mortality risks as normal weight-fit
      individuals. Furthermore, the obesity paradox may not influence fit individuals.
      Researchers, clinicians, and public health officials should focus on physical
      activity and fitness-based interventions rather than weight-loss driven
      approaches to reduce mortality risk. 

PMID- 24438730
TI  - Impact of obesity and weight loss on cardiac performance and morphology in
      adults.
AB  - Obesity, particularly severe obesity is capable of producing hemodynamic
      alterations that predispose to changes in cardiac morphology and ventricular
      function. These include increased cardiac output, left ventricular hypertrophy
      and diastolic and systolic dysfunction of both ventricles. Facilitated by co
      morbidities such as hypertension, the sleep apnea/obesity hypoventilation
      syndrome, and possibly certain neurohormonal and metabolic alterations, these
      abnormalities may predispose to left and right heart failure, a disorder known as
      obesity cardiomyopathy. 

PMID- 24438731
TI  - The impact of obesity on risk factors and prevalence and prognosis of coronary
      heart disease-the obesity paradox.
AB  - Obesity is associated with a host of cardiovascular risk factors and its
      prevalence is rising rapidly. Despite strong evidence that obesity predisposes to
      the development and progression of coronary heart disease (CHD), numerous studies
      have shown an inverse relationship between various measures of obesity (most
      commonly body mass index) and outcomes in established CHD. In this article we
      review the evidence surrounding the ?obesity paradox? in the secondary care of
      CHD patients and the CHD presentations where a paradox has been found. Finally we
      discuss the impact of cardiorespiratory fitness and a number of mechanisms which
      may offer potential explanations for this puzzling phenomenon. 

PMID- 24438732
TI  - Obesity and the obesity paradox in heart failure.
AB  - Obesity is a growing public health problem in the general population, and
      significantly increases the risk for the development of new-onset heart failure
      (HF). However, in the setting of chronic HF, overweight and mild to moderate
      obesity is associated with substantially improved survival compared to normal
      weight patients. Evidence exists for an "obesity paradox" in HF, with the
      majority of data measuring obesity by body mass index, but also across various
      less-frequently used measures of body fat (BF) and body composition including
      waist circumference, waist-hip ratio, skinfold estimates of percent BF, and
      bioelectrical impedance analysis of body composition. Other emerging areas of
      investigation such as the relationship of the obesity paradox to
      cardiorespiratory fitness are also discussed. Finally, this review explores
      various explanations for the obesity paradox, and summarizes the current evidence
      for intentional weight loss treatments for HF in context. 

PMID- 24438734
TI  - The concept of normal weight obesity.
AB  - Individuals with normal body weight by body mass index (BMI) and high body fat
      percentage show a high degree of metabolic dysregulation. This phenomenon,
      defined as normal weight obesity, is associated with a significantly higher risk
      of developing metabolic syndrome, cardiometabolic dysfunction and with higher
      mortality. Recently, we have also shown that coronary artery disease patients
      with normal BMI and central obesity have the highest mortality risk as compared
      to other adiposity patterns. Therefore, it is important to recognize these high
      risk groups for better adiposity-based risk stratification. There is a need for
      an updated definition of obesity based on adiposity, not on body weight. 

PMID- 24438733
TI  - Obesity paradox in end-stage kidney disease patients.
AB  - In the general population, obesity is associated with increased cardiovascular
      risk and decreased survival. In patients with end-stage renal disease (ESRD),
      however, an "obesity paradox" or "reverse epidemiology" (to include lipid and
      hypertension paradoxes) has been consistently reported, i.e. a higher body mass
      index (BMI) is paradoxically associated with better survival. This survival
      advantage of large body size is relatively consistent for hemodialysis patients
      across racial and regional differences, although published results are mixed for
      peritoneal dialysis patients. Recent data indicate that both higher skeletal
      muscle mass and increased total body fat are protective, although there are mixed
      data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely
      to be due to residual confounding alone and has biologic plausibility. Possible
      causes of the obesity paradox include protein-energy wasting and inflammation,
      time discrepancy among competitive risk factors (undernutrition versus
      overnutrition), hemodynamic stability, alteration of circulatory cytokines,
      sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein
      interaction. The obesity paradox may have significant clinical implications in
      the management of ESRD patients especially if obese dialysis patients are forced
      to lose weight upon transplant wait-listing. Well-designed studies exploring the
      causes and consequences of the reverse epidemiology of cardiovascular risk
      factors, including the obesity paradox, among ESRD patients could provide more
      information on mechanisms. These could include controlled trials of nutritional
      and pharmacologic interventions to examine whether gain in lean body mass or even
      body fat can improve survival and quality of life in these patients. 

PMID- 24438735
TI  - Contribution of cardiorespiratory fitness to the obesity paradox.
AB  - Until recently, cardiorespiratory fitness (CRF) has been overlooked as a
      potential modifier of the inverse association between obesity and mortality (the
      so-called obesity paradox), observed in patients with known or suspected
      cardiovascular (CV) disease. Evidence from five observational cohort studies of
      30,104 patients (87% male) with CV disease indicates that CRF significantly
      alters the obesity paradox. There is general agreement across studies that the
      obesity paradox persists among patients with low CRF, regardless of whether
      adiposity is assessed by body mass index, waist circumference, or percentage body
      fat. However, among patients with high CRF, risk of all-cause mortality is lowest
      for the overweight category in some, but not all, studies, suggesting that higher
      levels of fitness may modify the relationship between body fatness and survival
      in patients manifesting an obesity paradox. Further study is needed to better
      characterize the joint contribution of CRF and obesity on mortality in diverse
      populations. 

PMID- 24438736
TI  - The role of exercise and physical activity in weight loss and maintenance.
AB  - This review explores the role of physical activity (PA) and exercise training
      (ET) in the prevention of weight gain, initial weight loss, weight maintenance,
      and the obesity paradox. In particular, we will focus the discussion on the
      expected initial weight loss from different ET programs, and explore
      intensity/volume relationships. Based on the present literature, unless the
      overall volume of aerobic ET is very high, clinically significant weight loss is
      unlikely to occur. Also, ET also has an important role in weight regain after
      initial weight loss. Overall, aerobic ET programs consistent with public health
      recommendations may promote up to modest weight loss (~2 kg), however the weight
      loss on an individual level is highly heterogeneous. Clinicians should educate
      their patients on reasonable expectations of weight loss based on their physical
      activity program and emphasize that numerous health benefits occur from PA
      programs in the absence of weight loss.

PMID- 24438737
TI  - Potential benefits of weight loss in coronary heart disease.
AB  - The prevalence of overweight, obesity and insulin resistance in patients with
      coronary heart disease (CHD) exceeds that of the general population. Obesity is
      associated with a constellation of coronary risk factors that predispose to the
      development and progression of CHD. Intentional weight loss, accomplished through
      behavioral weight loss and exercise, improves insulin sensitivity and associated
      cardio-metabolic risk factors such as lipid measures, blood pressure, measures of
      inflammation and vascular function both in healthy individuals and patients with
      CHD. Additionally, physical fitness, physical function and quality of life all
      improve. There is evidence that intentional weight loss prevents the onset of CHD
      in high risk overweight individuals. While weight loss associated improvements in
      insulin resistance, fitness and related risk factors strongly supports favorable
      prognostic effects in individuals with established CHD, further study is needed
      to determine if long-term clinical outcomes are improved. 

PMID- 24438738
TI  - Evaluation of cardiorespiratory fitness and respiratory muscle function in the
      obese population.
AB  - Cardiorespiratory fitness (CRF) is one of the most important health metrics in
      apparently healthy individuals, those at increased risk for cardiovascular (CV)
      disease and virtually all patient populations. In addition to CRF, a host of
      other variables obtained from aerobic exercise testing provides clinically
      valuable information. Individuals classified as obese (i.e. a body mass index
      >=30 kg/m(2)) have varying degrees of CV, pulmonary and skeletal muscle
      dysfunction that impact CRF and other key aerobic exercise testing variables.
      Moreover, there is now evidence indicating inspiratory and expiratory respiratory
      muscle function, even in the absence of interstitial lung disease, is potentially
      compromised as a result of obesity. When obesity-induced respiratory muscle
      dysfunction is present, it has the potential to contribute to the limitations in
      CRF. The current review will discuss aerobic exercise testing and the assessment
      of respiratory muscle function in the obese population.

PMID- 24438739
TI  - Weight loss strategies for treatment of obesity.
AB  - Obesity is one of the most serious and prevalent non-communicable diseases of the
      21st century. It is also a patient-centered condition in which affected
      individuals seek treatment through a variety of commercial, medical and surgical
      approaches. Considering obesity as a chronic medical disease state helps to frame
      the concept of using a three-stepped intensification of care approach to weight
      management. As a foundation, all patients should be counseled on evidence-based
      lifestyle approaches that include diet, physical activity and behavior change
      therapies. At the second tier, two new pharmacological agents, phentermine
      topiramate and lorcaserin, were approved in 2012 as adjuncts to lifestyle
      modification. The third step, bariatric surgery, has been demonstrated to be the
      most effective and long-term treatment for individuals with severe obesity or
      moderate obesity complicated by comorbid conditions that is not responsive to non
      surgical approaches. By using a medical model, clinicians can provide more
      proactive and effective treatments in assisting their patients with weight loss. 

PMID- 24438740
TI  - A retrospective analysis of securing autologous split-thickness skin grafts with
      negative pressure wound therapy in paediatric burn patients.
AB  - BACKGROUND AND AIM: Deep dermal and full-thickness burn wounds are excised and
      grafted with split-thickness skin grafts. Especially in less compliant patients
      such as young children, conventional fixing methods can often be ineffective due
      to high mobility rates in this age group. The aim of this retrospective single
      centre study was to give an overview of our experience in the fixation of
      autologous split-thickness skin grafts (ASTSGs) on burn wounds by negative
      pressure wound therapy (NPWT) in paediatric patients. METHODS: A retrospective
      analysis describing 53 paediatric patients with burns or burn-related injuries
      who were treated as 60 individual cases were conducted. All patients received
      ASTSGs secured by NPWT. RESULTS: Of the individual cases, 60 cases with a mean
      age of 8+/-6 years (the youngest was 3 months, the eldest was 24 years old) were
      treated in a single procedure with ASTSG and NPWT. Total burn surface area (TBSA)
      was, median (med) 4.5% (3.0-12.0%). The TBSA of deep dermal thickness to full
      thickness (IIb-III degrees ) burns was med 4.0% (2.0-6.0%). The TBSA treated with
      ASTSG and NPWT was med 3.5% (2.0-6.0%). Take rate was, med 96% (90-99%) with a
      total range of 70-100%. The only significant correlation that could be found was
      between the grafted TBSA and the take rate. The smaller the grafted TBSA the
      better the take rate resulted, as expected. In three cases, major complications
      were noted. CONCLUSION: To sum up our experience, the NPWT system has developed
      itself to be a constant, well-implemented and useful tool in securing ASTSGs to
      the wound bed. The main advantage of the technique is a much higher mobility of
      the patient compared to conventional fixation methods. The high compliance rate
      of an often challenging group of patients such as children recompenses possible
      higher costs compared to conventional fixation methods.

PMID- 24438741
TI  - "Is the length of time in acute burn surgery associated with poorer outcomes?".

PMID- 24438743
TI  - Symptom clusters in patients on dialysis and their association with quality-of
      life outcomes.
AB  - BACKGROUND: Patients who are on dialysis report multiple symptoms. The aim of the
      study was to explore and identify symptom clusters (co-occurring symptoms) in
      patients on dialysis and their possible associations with depressive symptoms and
      health-related quality-of-life (HRQOL) outcomes. METHODS: In a cross-sectional
      study of 301 prevalent patients on dialysis, physical symptoms, depressive
      symptoms and HRQOL were assessed using the Beck Depression Inventory (BDI) and
      the Kidney Disease and Quality-of-Life-Short Form version 1.3 (KDQOL-SF36)
      questionnaires. Symptom clusters were identified using principal component
      analysis with varimax rotation. Multivariate linear regression analyses were
      carried out to evaluate the relationships between symptom clusters and depressive
      symptoms and HRQOL outcomes. RESULTS: The majority of patients (63.5%) rated
      their symptoms in the 'very much' to 'extremely bothersome' range, and 29.4% had
      significant depressive symptoms. Three symptom clusters were identified and were
      named uraemic (nausea, lack of appetite, dizziness/faintness, feeling squeezed
      out, shortness of breath, chest pain), neuromuscular (numbness in extremities,
      sore muscles, cramps) and skin (itching, dry skin) clusters. The three clusters
      were associated with BDI, physical component summary (PCS) and mental component
      summary (MCS) scores. After multiple adjustments, the uraemic and neuromuscular
      clusters remained independently associated with BDI and PCS scores and the
      uraemic and skin clusters with MCS scores. CONCLUSION: The strong associations
      between symptom clusters and depressive symptoms and the physical and mental
      domains of HRQOL should lead to an increased focus on symptom-alleviating
      interventions. Additional research is warranted to determine whether treatment of
      symptom clusters rather than single symptoms will improve HRQOL.

PMID- 24438744
TI  - A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily
      long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the
      GLOW5 study.
AB  - BACKGROUND: Two once-daily long-acting muscarinic antagonists (LAMAs) are
      currently available for the treatment of chronic obstructive pulmonary disease
      (COPD) - tiotropium and glycopyrronium. Previous studies have compared
      glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare
      glycopyrronium with blinded tiotropium. METHODS: In this blinded, double-dummy,
      parallel group, 12-week study, patients with moderate-to-severe COPD were
      randomized 1:1 to glycopyrronium 50 MUg once daily or tiotropium 18 MUg once
      daily. The primary objective was to demonstrate the non-inferiority of
      glycopyrronium versus blinded tiotropium with respect to trough forced expiratory
      volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority
      margin: -50 mL). Secondary objectives were to evaluate glycopyrronium versus
      tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea
      Index; TDI), health status (St George's Respiratory Questionnaire; SGRQ), daily
      rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of
      treatment. RESULTS: 657 patients were randomized (glycopyrronium: 327;
      tiotropium: 330); 96% (630 patients) completed the study. Least squares mean
      trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12,
      meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95%
      CI: -32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following
      first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h
      post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0-4 h
      (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium
      on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium
      demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total
      score, rescue medication use and the rate of COPD exacerbations (all p = not
      significant). Patients on glycopyrronium also had a significantly lower total
      COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).
      Adverse events were reported by a similar percentage of patients receiving
      glycopyrronium (40.4%) and tiotropium (40.6%). CONCLUSION: In patients with
      moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium
      50 MUg or tiotropium 18 MUg, provided similar efficacy and safety, with
      glycopyrronium having a faster onset of action on Day 1 versus tiotropium.

PMID- 24438742
TI  - New molecular medicine-based scar management strategies.
AB  - Keloids and hypertrophic scars are prevalent disabling conditions with still
      suboptimal treatments. Basic science and molecular-based medicine research have
      contributed to unravel new bench-to-bedside scar therapies and to dissect the
      complex signalling pathways involved. Peptides such as the transforming growth
      factor beta (TGF-beta) superfamily, with Smads, Ski, SnoN, Fussels, endoglin, DS
      Sily, Cav-1p, AZX100, thymosin-beta4 and other related molecules may emerge as
      targets to prevent and treat keloids and hypertrophic scars. The aim of this
      review is to describe the basic complexity of these new molecular scar management
      strategies and point out new fibrosis research lines. 

PMID- 24438745
TI  - Induction of nerve growth factor expression and release by mechanical and
      inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis
      pain.
AB  - INTRODUCTION: Nerve growth factor (NGF) level is increased in osteoarthritis (OA)
      joints and is involved in pain associated with OA. Stimuli responsible for NGF
      stimulation in chondrocytes are unknown. We investigated whether mechanical
      stress and proinflammatory cytokines may influence NGF synthesis by chondrocytes.
      METHODS: Primary cultures of human OA chondrocytes, newborn mouse articular
      chondrocytes or cartilage explants were stimulated by increasing amounts of IL
      1beta, prostaglandin E2 (PGE2), visfatin/nicotinamide phosphoribosyltransferase
      (NAMPT) or by cyclic mechanical compression (0.5 Hz, 1 MPa). Before stimulation,
      chondrocytes were pretreated with indomethacin, Apo866, a specific inhibitor of
      NAMPT enzymatic activity, or transfected by siRNA targeting visfatin/NAMPT. mRNA
      NGF levels were assessed by real-time quantitative PCR and NGF released into
      media was determined by ELISA. RESULTS: Unstimulated human and mouse articular
      chondrocytes expressed low levels of NGF (19.2 +/- 8.7 pg/mL, 13.5 +/- 1.0 pg/mL
      and 4.4 +/- 0.8 pg/mL/mg tissue for human and mouse articular chondrocytes and
      costal explants, respectively). Mechanical stress induced NGF release in
      conditioned media. When stimulated by IL-1beta or visfatin/NAMPT, a
      proinflammatory adipokine produced by chondocytes in response to IL-1beta, a dose
      dependent increase in NGF mRNA expression and NGF release in both human and mouse
      chondrocyte conditioned media was observed. Visfatin/NAMPT is also an
      intracellular enzyme acting as the rate-limiting enzyme of the generation of NAD.
      The expression of NGF induced by visfatin/NAMPT was inhibited by Apo866, whereas
      IL-1beta-mediated NGF expression was not modified by siRNA targeting
      visfatin/NAMPT. Interestingly, PGE2, which is produced by chondrocytes in
      response to IL-1beta and visfatin/NAMPT, did not stimulate NGF production.
      Consistently, indomethacin, a cyclooxygenase inhibitor, did not counteract IL
      1beta-induced NGF production. CONCLUSIONS: These results show that mechanical
      stress, IL-1beta and extracellular visfatin/NAMPT, all stimulated the expression
      and release of NGF by chondrocytes and thus suggest that the overexpression of
      visfatin/NAMPT and IL-1beta in the OA joint and the increased mechanical loading
      of cartilage may mediate OA pain via the stimulation of NGF expression and
      release by chondrocytes.

PMID- 24438747
TI  - Incidence and cost of workplace violence.

PMID- 24438746
TI  - Chromatin and beyond: the multitasking roles for SIRT6.
AB  - In recent years there has been a large expansion in our understanding of SIRT6
      biology including its structure, regulation, biochemical activity, and biological
      roles. SIRT6 functions as an ADP-ribosylase and NAD(+)-dependent deacylase of
      both acetyl groups and long-chain fatty-acyl groups. Through these functions
      SIRT6 impacts upon cellular homeostasis by regulating DNA repair, telomere
      maintenance, and glucose and lipid metabolism, thus affecting diseases such
      diabetes, obesity, heart disease, and cancer. Such roles may contribute to the
      overall longevity and health of the organism. Until recently, the known functions
      of SIRT6 were largely restricted to the chromatin. In this article we seek to
      describe and expand this knowledge with recent advances in understanding the
      mechanisms of SIRT6 action and their implications for human biology and disease. 

PMID- 24438748
TI  - Quantification of mitral regurgitation by general imaging three-dimensional
      quantification: feasibility and accuracy.
AB  - BACKGROUND: Mitral regurgitant volume (MRvol) is an important index of the
      severity of mitral regurgitation (MR), but MRvol measurement remains challenging.
      With the development of probe technology and software, General Imaging 3D
      Quantification (GI 3DQ) allows the direct measurement of MR jet volume. The aim
      of this study was to evaluate the feasibility and accuracy of MRvol by
      quantification of MR jet volume using GI 3DQ. METHODS: Ninety-three patients were
      included, 61 with functional MR and 32 with mitral valve prolapse. Patients with
      MR were also divided into those with central MR (n = 41) and those with eccentric
      MR (n = 52). MRvol was assessed using GI 3DQ and the proximal isovelocity surface
      area (PISA) method. MRvol using effective regurgitant orifice area by real-time
      three-dimensional echocardiography multiplied by the MR time-velocity integral
      was used as the reference method. RESULTS: MRvol measured by GI 3DQ and the PISA
      method had good correlation with MRvol by the reference method. A significant
      underestimation of MRvol using GI 3DQ and the PISA method was observed in the
      assessment of eccentric MR, but without a significant difference in the
      assessment of central MR. CONCLUSIONS: Quantification of MRvol with GI 3DQ was
      feasible. Quantification of central MRvol using this methodology is accurate
      compared with the reference method. Quantification of MRvol with GI 3DQ has no
      significant difference from the currently recommended PISA method.

PMID- 24438749
TI  - Authors' reply.

PMID- 24438750
TI  - Authors' reply.

PMID- 24438751
TI  - Doppler echocardiography inaccurately estimates right ventricular pressure in
      children with elevated right heart pressure.

PMID- 24438752
TI  - Limitations of current nomograms in pediatric echocardiography: just the tip of
      the iceberg--a call for standardization.

PMID- 24438753
TI  - The use of seaweed from the Galician coast as a mineral supplement in organic
      dairy cattle.
AB  - This study was designed to assess the value of seaweeds from the Galician coast
      as a source of minerals (especially iodine (I) but also other micro-minerals) in
      organic dairy cattle. It was conducted in an organic dairy farm in the Lugo
      province that typically represents the organic milk production in NW Spain. The
      animal's diet consisted mainly of local forage (at pasture or as hay and silage
      in the winter) and 5 kg of purchased concentrate/day per animal (representing
      23.5% of feed intake). Based on the mineral composition of the diet, the
      physiological requirements and the EU maximum authorised levels in feed, a
      supplement composed by Sea Lettuce (Ulva rigida) (as flakes, 80%), Japanese
      Wireweed (Sargasum muticum) (flakes, 17.5%) and Furbelows (Saccorhiza
      polyschides) (powder, 2.5%) was formulated to give 100 g/animal per day. Sixteen
      Holstein Friesian lactating cows were randomly selected and assigned to the
      control (n=8) and algae-supplemented groups (n=8). Both groups had exactly the
      same feeding and management with the exception of the algae supplement, which was
      mixed with the concentrate feed and given to the animals at their morning milking
      for 10 weeks. Heparinised blood (for plasma analysis) and milk samples were
      collected at 2-week intervals and analysed for toxic and trace element
      concentrations by inductively coupled plasma-mass spectrometry or inductively
      coupled plasma-optical emission spectrometry. The algae supplement significantly
      improved the animals' mineral status, particularly I and selenium that were low
      on the farm. However, the effect of the algae supplement on the molybdenum status
      in cattle needs further investigation because of its great relevance on copper
      metabolism in ruminants. The I supply deserves special attention, since this
      element is at a very high concentration in brown-algae species and it is excreted
      in the milk proportionally to its concentration in plasma concentrations (mean +/
      s.e. in the algae-supplemented and control groups were 268 +/- 54 and 180 +/- 42
      ug/l, respectively).

PMID- 24438755
TI  - Whole-body retention of alpha-linolenic acid and its apparent conversion to other
      n-3 PUFA in growing pigs are reduced with the duration of feeding alpha-linolenic
      acid.
AB  - In the present study, fifteen growing pigs were used to determine the whole-body
      oxidation, retention efficiency (RE) and apparent conversion (AC) of alpha
      linolenic acid (18 : 3n-3) to n-3 highly unsaturated fatty acids (HUFA),
      including EPA (20 : 5n-3) and DHA (22 : 6n-3). The pigs were fed a diet
      containing 10% flaxseed for 30 d. Whole-body fatty acid composition was
      determined at initial (27.7 (SE 1.9) kg), intermediate (day 15; 39.2 (SE 1.4) kg)
      and final (45.7 (SE 2.2) kg) body weight. On day 12, four pigs were fed 10 mg/kg
      of uniformly labelled (13)C-18 : 3n-3 (single-bolus dose) to determine the
      oxidation of 18 : 3n-3. Expired CO2 samples were collected for 24 h thereafter.
      The whole-body content of n-3 PUFA increased linearly (P< 0.0001) with time;
      however, the content of 22 : 6n-3 exhibited a quadratic response (P< 0.01) with a
      peak occurring at 15 h. As a proportion of intake, the RE of 18 : 3n-3 tended to
      reduce with time (P = 0.098). The AC of ingested 18 : 3n-3 to the sum of n-3 HUFA
      was reduced with time (P< 0.05; 12.2 v. 7.53 % for days 0-15 and days 15-30,
      respectively). The AC of 18 : 3n-3 to 20 : 5n-3 or 22 : 6n-3 was lower than that
      to 20 : 3n-3, both for days 0-15 (P < 0.05; 1.14 or 1.07 v. 7.06 %) and for days
      15-30 (P< 0.05; 1.51 or 0.33 v. 4.29 %). The direct oxidation of 18 : 3n-3 was
      7.91 (SE 0.98) % and was similar to the calculated disappearance of 18 : 3n-3
      between days 0 and 30 (8.81 (SE 5.24) %). The oxidation of 18 : 3n-3 was much
      lower than that reported in other species. The AC of 18 : 3n-3 to n-3 HUFA was
      reduced over time and that to 20 : 3n-3 in the present study was much higher than
      that reported in other species and should be explored further.

PMID- 24438754
TI  - Adapting iron dose supplementation in pregnancy for greater effectiveness on
      mother and child health: protocol of the ECLIPSES randomized clinical trial.
AB  - BACKGROUND: Currently, there is no consensus regarding iron supplementation dose
      that is most beneficial for maternal and offspring health during gestation.
      Recommended iron supplementation dose does not preempt anemia in around 20% of
      the pregnancies, nor the risk of hemoconcentration in 15%. This deficit, or
      excess, of iron prejudices the mother-child wellbeing. Therefore the aims of the
      study are to determine the highest level of effectiveness of iron supplementation
      adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for
      mother-child health. METHODS/DESIGN:  DESIGN: Randomized Clinical Trial (RCT)
      triple-blindedSetting: 10 Primary Care Centers from Catalunya (Spain)Study
      subjects: 878 non-anemic pregnant women at early gestation stage, and their
      subsequent newborns METHODS: The study is structured as a RCT with 2 strata,
      depending on the Hb levels before week 12 of gestation. Stratum #1: If Hb from
      110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or
      80 mg/d. Stratum #2: If Hb >130 g/L, randomly assigned at week 12 to receive iron
      supplement of 40 or 20 mg/d. MEASUREMENTS: In the mother: socio-economic data,
      clinical history, food item frequency, lifestyle and emotional state, and
      adherence to iron supplement prescription. Biochemical measurements include: Hb,
      serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene
      (C282Y, H63D). In children: ultrasound fetal biometry, anthropometric
      measurements, and temperament development.Statistical analyses, using the SPSS
      program for Windows, will include bivariate and multivariate analyses adjusted
      for variables associated with the relationship under study. DISCUSSION: Should
      conclusive outcomes be reached, the study would indicate the optimal iron
      supplementation dose required to promote maternal and infant health. These
      results would contribute towards developing guidelines for good clinical
      practice.

PMID- 24438756
TI  - Emergency right hemicolectomy for inflammatory cecal masses mimicking acute
      appendicitis.
AB  - BACKGROUND: Unexpected inflammatory cecal masses of uncertain etiology,
      encountered in the emergency surgical departments can be indistinguishable, and
      appropriate operative management of these cases is a dilemma for the surgeons.
      METHODS: Over a 30-months period between January 2009 and June 2011, a series of
      3032 patients who live in sub-urban underwent emergency surgery for clinical
      diagnosis of acute appendicitis and ileocecal resection or right hemicolectomy
      for inflammatory cecal mass were performed in 48 patients. RESULTS: 28 men and 20
      women from suburban between ages 16-73 presented with right iliac fossa pain. The
      major presenting symptom was pain in the right iliac fossa (100%). On physical
      examination; tenderness at or near the McBurney point was detected in 44 (91,6%)
      patients. The range of the leucocyte level was between 8.000 to 24.000 and mean
      level is 16.000. After initial laparoscopic exploration, ileocecal resection or
      right hemicolectomy was performed conservatively because of the uncertainty of
      the diagnosis. Overall 32 patients underwent ileocecal resection and 16 patients
      underwent right hemicolectomy. Pathology revealed appendicular phlegmon in 18
      patients, perforated cecal diverticulitis in 12 patients, tuberculosis in 6
      patients, appendiceal and cecal rupture in 4 patients, malign mesenquimal
      neoplasm in 4 patients, non-spesific granulomatous in 2 patients and appendecular
      endometriosis in 2 patients. CONCLUSION: Most inflammatory cecal masses are due
      to benign pathologies and can be managed safely and sufficiently with ileocecal
      resection or right hemicolectomy. The choice of the surgical procedure depends on
      the experience of the surgical team.

PMID- 24438763
TI  - Transforming Australia's HIV prevention and treatment efforts to achieve an AIDS
      free generation: the United Nations Political Declaration on HIV/AIDS and the
      Melbourne Declaration 'Action on HIV'.
AB  - This paper discusses Australia's response to the 2011 United Nations Political
      Declaration on HIV/AIDS in the context of recent ground-breaking advances in HIV
      prevention and treatment. Australia's progress in responding to these
      developments is examined and compared with that of eight other countries in Asia
      and the Pacific. The implications of the 2012 Melbourne Declaration 'Action on
      HIV' is also discussed as a vehicle for generating advocacy to revolutionise
      Australia's HIV response and to urge Australia's leadership in achieving an 'AIDS
      free generation'. 

PMID- 24438764
TI  - The calmodulin intergenic spacer as molecular target for characterization of
      Leishmania species.
AB  - BACKGROUND: Human leishmaniasis is a neglected disease caused by parasites of the
      genus Leishmania. Clinical aspects of this disease can vary significantly,
      reflecting the wide range of parasites in the genus Leishmania. Knowing
      accurately the Leishmania species infecting humans is important for clinical case
      management and evaluation of epidemiological risk. Calmodulin is an essential
      gene in trypanosomatids that modulates the calcium metabolism in various cellular
      activities. Despite its strong conservation in trypanosomatids, it has been
      recently observed that its untranslated regions (UTR) diverge among species.
      METHODS: In this study we analyzed the sequences and the absolute dinucleotide
      frequency of the intergenic spacer of the calmodulin gene (containing both, 3'
      and 5'UTR) in nine reference Leishmania species and ten clinical isolates
      obtained from patients with cutaneous leishmaniasis. RESULTS: We show that the
      short calmodulin intergenic spacers exhibit features that make them interesting
      for applications in molecular characterization and phylogenetic studies of
      Leishmania. Dendrograms based on sequence alignments and on the dinucleotide
      frequency indicate that this particular region of calmodulin gene might be useful
      for species typing between the Leishmania and Viannia subgenera. CONCLUSIONS:
      Mutations and composition of the calmodulin intergenic spacer from Leishmania
      species might have taxonomic value as parameters to define if an isolate is
      identical to a certain species or belongs to one of the two current subgenera.

PMID- 24438767
TI  - Biaxial mechanical testing of posterior sclera using high-resolution ultrasound
      speckle tracking for strain measurements.
AB  - This study aimed to characterize the mechanical responses of the sclera, the
      white outer coat of the eye, under equal-biaxial loading with unrestricted shear.
      An ultrasound speckle tracking technique was used to measure tissue deformation
      through sample thickness, expanding the capabilities of surface strain
      techniques. Eight porcine scleral samples were tested within 72 h postmortem.
      High resolution ultrasound scans of scleral cross-sections along the two loading
      axes were acquired at 25 consecutive biaxial load levels. An additional repeat of
      the biaxial loading cycle was performed to measure a third normal strain
      emulating a strain gage rosette for calculating the in-plane shear. The
      repeatability of the strain measurements during identical biaxial ramps was
      evaluated. A correlation-based ultrasound speckle tracking algorithm was used to
      compute the displacement field and determine the distributive strains in the
      sample cross-sections. A Fung type constitutive model including a shear term was
      used to determine the material constants of each individual specimen by fitting
      the model parameters to the experimental stress-strain data. A non-linear stress
      strain response was observed in all samples. The meridian direction had
      significantly larger strains than that of the circumferential direction during
      equal-biaxial loadings (P's<0.05). The stiffness along the two directions was
      also significantly different (P=0.02) but highly correlated (R(2)=0.8). These
      results showed that the mechanical properties of the porcine sclera were
      nonlinear and anisotropic under biaxial loading. This work has also demonstrated
      the feasibility of using ultrasound speckle tracking for strain measurements
      during mechanical testing.

PMID- 24438769
TI  - New efficacy of LTRAs (montelukast sodium): it possibly prevents food-induced
      abdominal symptoms during oral immunotherapy.
AB  - BACKGROUND: The aim of the study was to elucidate whether leukotriene receptor
      antagonists (LTRAs) can prevent severe allergic reactions, which occur during
      oral immunotherapy (OIT) in children with food allergies. FINDINGS: Five children
      with food allergies [3 allergic to hen's egg (HE), 1 to wheat, and one to cow's
      milk (CM); aged between 7 and 12 years; median, 8.5 years] who were started on
      LTRAs during OIT were retrospectively selected from among 63 children undergoing
      OIT. In the rush phase, after the administration of the initial dose which was
      set in open food challenge test, the subsequent doses were increased by
      approximately 1.2 times of the previous dose and were administered every 2 hours,
      4 times a day. The target doses of hen's egg, wheat (udon noodle), and cow's milk
      in the rush phase were 50 g, 200 g, and 200 ml, respectively. The ingestion of
      the target dose was continued at home every day for at least a year in the
      maintained phase.Four participants experienced intractable abdominal pain during
      the rush phase; therefore, the loading dose was not increased in these children.
      However, the administration of LTRAs prevented their symptoms, resulting in the
      completion of the rush phase. One participant also experienced intractable
      abdominal pain during the maintenance phase. After receiving LTRAs, the target
      dose was able to tolerated. CONCLUSION: The findings from this retrospective
      study suggest that the administration of LTRAs is useful for the prevention of
      adverse allergic reactions such as abdominal pain during OIT.

PMID- 24438768
TI  - Elastic, permeability and swelling properties of human intervertebral disc
      tissues: A benchmark for tissue engineering.
AB  - The aim of functional tissue engineering is to repair and replace tissues that
      have a biomechanical function, i.e., connective orthopaedic tissues. To do this,
      it is necessary to have accurate benchmarks for the elastic, permeability, and
      swelling (i.e., biphasic-swelling) properties of native tissues. However, in the
      case of the intervertebral disc, the biphasic-swelling properties of individual
      tissues reported in the literature exhibit great variation and even span several
      orders of magnitude. This variation is probably caused by differences in the
      testing protocols and the constitutive models used to analyze the data.
      Therefore, the objective of this study was to measure the human lumbar disc
      annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplates (CEP)
      biphasic-swelling properties using a consistent experimental protocol and
      analyses. The testing protocol was composed of a swelling period followed by
      multiple confined compression ramps. To analyze the confined compression data,
      the tissues were modeled using a biphasic-swelling model, which augments the
      standard biphasic model through the addition of a deformation-dependent osmotic
      pressure term. This model allows considering the swelling deformations and the
      contribution of osmotic pressure in the analysis of the experimental data. The
      swelling stretch was not different between the disc regions (AF: 1.28+/-0.16; NP:
      1.73+/-0.74; CEP: 1.29+/-0.26), with a total average of 1.42. The aggregate
      modulus (Ha) of the extra-fibrillar matrix was higher in the CEP (390kPa)
      compared to the NP (100kPa) or AF (30kPa). The permeability was very different
      across tissue regions, with the AF permeability (64 E(-16)m(4)/Ns) higher than
      the NP and CEP (~5.5 E(-16)m(4)/Ns). Additionally, a normalized time-constant
      (3000s) for the stress relaxation was similar for all the disc tissues. The
      properties measured in this study are important as benchmarks for tissue
      engineering and for modeling the disc's mechanical behavior and transport. 

PMID- 24438770
TI  - [Status and expertise of off-label use of misoprostol in obstetrics and
      gynecology in France: study by CNGOF (short text)].

PMID- 24438771
TI  - Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo
      controlled trial.
AB  - The role of calcifediol in the perception of chronic pain is a widely discussed
      subject. Low serum levels of calcifediol are especially common in patients with
      severe pain and fibromyalgia syndrome (FMS). We lack evidence of the role of
      vitamin D supplementation in these patients. To our knowledge, no randomized
      controlled trial has been published on the subject. Thirty women with FMS
      according to the 1990 and 2010 American College of Rheumatology criteria, with
      serum calcifediol levels <32ng/mL (80nmol/L), were randomized to treatment group
      (TG) or control group (CG). The goal was to achieve serum calcifediol levels
      between 32 and 48ng/mL for 20weeks via oral supplementation with cholecalciferol.
      The CG received placebo medication. Re-evaluation was performed in both groups
      after a further 24weeks without cholecalciferol supplementation. The main
      hypothesis was that high levels of serum calcifediol should result in a reduction
      of pain (visual analog scale score). Additional variables were evaluated using
      the Short Form Health Survey 36, the Hospital Anxiety and Depression Scale, the
      Fibromyalgia Impact Questionnaire, and the Somatization subscale of Symptom
      Checklist-90-Revised. A marked reduction in pain was noted over the treatment
      period in TG: a 2 (groups)*4 (time points) variance analysis showed a significant
      group effect in visual analog scale scores. This also was correlated with scores
      on the physical role functioning scale of the Short Form Health Survey 36.
      Optimization of calcifediol levels in FMS had a positive effect on the perception
      of pain. This economical therapy with a low side effect profile may well be
      considered in patients with FMS. However, further studies with larger patient
      numbers are needed to prove the hypothesis. 

PMID- 24438772
TI  - Still making a mark? Fingerprints in the 21st century.

PMID- 24438773
TI  - Development and validation of highly selective screening and confirmatory methods
      for the qualitative forensic analysis of organic explosive compounds with high
      performance liquid chromatography coupled with (photodiode array and) LTQ ion
      trap/Orbitrap mass spectrometric detections (HPLC-(PDA)-LTQOrbitrap).
AB  - An LTQ-Orbitrap FTMS is a new (hybrid) mass spectrometric (MS) analyzer. It
      allows for the acquisition of full scan MS(n) (n-stage fragmentations, n=1-n)
      spectra with the linear ion trap detector (LTQ) at high speed and/or with the
      Fourier Transform-detector (Orbitrap) with ultra high mass resolution (>60,000 at
      m/z<400amu) and high mass accuracy (<=1ppm with internal calibration). In
      addition it may be coupled with liquid chromatography (LC) with photo diode array
      (PDA) detection. Two methods for the forensic screening and confirmation of all
      common trace explosives in post-blast residues have been developed on this
      instrument using atmospheric pressure chemical ionization (APCI). In one run, the
      nitrogen-containing explosives are analyzed with the combination of "LC-(PDA)
      APCI(-)-LTQ MS(2)/Orbitrap FTMS" (Method 1). In another run, peroxide explosives
      are analyzed with "LC-APCI(+)-LTQ MS(2)/Orbitrap FTMS" (Method 2). The
      performance of both methods has been validated according to procedures defined in
      the EU COMMISSION DECISION implementing Council Directive 96/23/EC concerning the
      performance of analytical methods and the interpretation of results (DC
      2002/657/EC) and other standards (NEN 17025 and NEN 7777). The methods are highly
      selective due to the simultaneous utilization of the Orbitrap FTMS and LTQ MS(2),
      both of which are highly selective detectors Tested explosive compounds can be
      detected in the molecular ion form by the Orbitrap analyzer with minimal mass
      interference in different matrices when using an extremely narrow mass tolerance
      detection window (<=2ppm). The identification of a detected compound follows an
      identification point system. Experimental results show that almost all explosive
      compounds meet the confirmation criteria (minimum 4 points) required for the
      positive identification by the DC 2002/657/EC. 

PMID- 24438774
TI  - Development of gas chromatography-mass spectrometry (GC-MS) and other rapid
      screening methods for the analysis of 16 'legal high' cathinone derivatives.
AB  - The prevalence of so-called 'legal high' drugs in forensic science drug casework
      has increased markedly in recent years. This has given rise to both legal and
      analytical challenges in the identification of these substances. The requirement
      for validated, reliable and rapid testing methodologies for these compounds is
      obvious. This work reports the analysis of sixteen synthesised cathinone
      derivatives encountered in casework using presumptive testing, thin layer
      chromatography and gas chromatography-mass spectrometry (GC-MS). 

PMID- 24438775
TI  - The use of organic and inorganic impurities found in MDMA police seizures in a
      drug intelligence perspective.
AB  - Traditional forensic drug profiling involves numerous analytical techniques, and
      the whole process is typically costly and may be time consuming. The aim of this
      study was to investigate the possibility of prioritising techniques utilised at
      the Australian Federal Police (AFP) for the chemical profiling of 3,4
      methylenedioxymethylamphetamine (MDMA). The outcome would provide the AFP with
      the ability to obtain more timely and valuable results that could be used in an
      intelligence perspective. Correlation coefficients were used to obtain a
      similarity degree between a population of linked samples (within seizures) and a
      population of unlinked samples (between different seizures) and discrimination
      between the two populations was ultimately achieved. The results showed that gas
      chromatography-mass spectrometry (GC-MS) was well suited as a single technique to
      detect links between seizures and could be used in priority for operational
      intelligence purposes. Furthermore, the method was applied to seizures known or
      suspected (through their case information) to be linked to each other to assess
      the chemical similarity between samples. It was found that half of the seizures
      previously linked by the case number were also linked by the chemical profile.
      This procedure was also able to highlight links between cases that were
      previously unsuspected and retrospectively confirmed by circumstantial
      information. The findings are finally discussed in the broader forensic
      intelligence context, with a focus on how they could be successfully incorporated
      into investigations and in an intelligence-led policing perspective in order to
      understand trafficking markets. 

PMID- 24438776
TI  - Preparation of cyanoacrylate derivatives and comparison of dual action
      cyanoacrylate formulations.
AB  - The use of cyanoacrylate followed by fluorescent reagents is well known in the
      field of fingermark visualisation. Treatment with fluorescent reagents that stain
      the cyanoacrylate deposits will not only enhance the visibility of fingermarks
      previously thought unusable, but also reveal previously unseen marks. Downside of
      this approach is the exposure of the evidential material to large amounts of
      solvent, such as water, methanol and ethanol, thereby potentially destroying
      other forensic traces. New cyanoacrylate derivates with fluorescent and UV-active
      properties can be used for one step dual action visualisation of latent
      fingermarks. Increased optical properties can be achieved by addition of
      functional groups via the Steglich esterification of cyanoacetic acid with N-(3
      dimetylaminopropyl)-N'-ethylcarbodiimide (EDC). The UV-active ester can be
      created via the Knoevenagel condensation with formaldehyde to form poly
      cyanoacrylate. These poly-cyanoacrylates can be depolymerised to form monomer
      cyanoacrylates. In this paper we compare these ethylcyanoacrylate derivatives
      with commercially available cyanoacrylate formulations. We have shown that the
      use of poly-cyanoacrylate derivatives can yield fully developed fingerprints. The
      initiator of the polymerisation reaction towards novel reagents can be altered
      according to the need for particular optical properties. 

PMID- 24438777
TI  - The spatial and temporal distribution of pollen in a room: forensic implications.
AB  - This paper presents two experimental studies that deal with the spatial and
      temporal distribution of pollen grains within a room of a domestic dwelling. The
      findings concur with the preliminary work of Morgan et al. [1] and provide
      greater detail as to the behaviour of pollen grains within indoor locations that
      are pertinent for forensic investigations. The spatial distribution of pollen in
      a room exhibits strong distance decay trends, with the majority of pollen
      recovered within 0.8m of its source. The pollen was found to persist in
      increasing quantities during the time the flowers were in the room. This study
      also shows that 20days after the flowers were removed, 25-32% of the original
      pollen was still present within the room. The influence of disturbance was
      investigated and whilst areas of high disturbance were found to retain less
      pollen than undisturbed locations, the influence of the proximity to source was a
      more dominant factor. These findings have significant implications for forensic
      investigation protocols, particularly the collection and interpretation phases of
      trace evidence analysis. The distribution of pollen around a room ensures that
      viable sources of trace pollen are available for transfer if contact is made
      between a location in the room and a suspect. The persistence of pollen many days
      after the flowers have been removed from a room indicates that many rooms in
      domestic dwellings will have distinctive assemblages that reflect the history of
      the flowers that have been displayed within that room in the past, and that these
      assemblages will persist and therefore be available for transfer. These
      preliminary findings indicate that investigation by forensic palynology in indoor
      domestic settings may well be an underutilised technique that has the potential
      to provide accurate and valuable intelligence and evidence for forensic enquiry. 

PMID- 24438778
TI  - Exhaled breath for drugs of abuse testing - evaluation in criminal justice
      settings.
AB  - Exhaled breath is being developed as a possible specimen for drug testing based
      on the collection of aerosol particles originating from the lung fluid. The
      present study was aimed to evaluate the applicability of exhaled breath for drugs
      of abuse testing in criminal justice settings. Particles in exhaled breath were
      collected with a new device in parallel with routine urine testing in two Swedish
      prisons, comprising both genders. Urine screening was performed according to
      established routines either by dipstick or by immunochemical methods at the
      Forensic Chemistry Laboratory and confirmations were with mass spectrometry
      methods. A total of 247 parallel samples were studied. Analysis of exhaled breath
      samples was done with a sensitive mass spectrometric method and identifications
      were made according to forensic standards. In addition tested subjects and
      personnel were asked to fill in a questionnaire concerning their views about drug
      testing. In 212 cases both the urine and breath testing were negative, and in 22
      cases both urine and breath were positive. Out of 6 cases where breath was
      negative and urine positive 4 concerned THC. Out of 7 cases where, breath was
      positive and urine negative 6 concerned amphetamine. Detected substances in
      breath comprised: amphetamine, methamphetamine, THC, methylphenidate,
      buprenorphine, 6-acetylmorphine, cocaine, benzoylecgonine, diazepam and tramadol.
      Both the prison inmates and staff members reported breath testing to be
      preferable due to practical considerations. The results of this study documented
      that drug testing using exhaled breath provided as many positives as urine
      testing despite an expected shorter detection window, and that the breath
      sampling procedure was well accepted and provided practical benefits reported
      both by the prison inmates and testing personnel. 

PMID- 24438779
TI  - Post-mortem evidence of doxylamine in toxicological analyses.
AB  - BACKGROUND: Doxylamine (DA) is widely available in pharmacies without
      prescription and can be used in suicidal intention because of its sedative and
      anticholinergic properties. Research of literature shows that only a few
      publications deal with post-mortem evidence of DA and its interpretation during
      toxicological examination. MATERIAL AND METHODS: In this study, all cases with a
      positive detection of DA during toxicological analyses with high-performance
      liquid chromatography in the time period 2000 to 2010 at the Institute of Legal
      Medicine and Forensic Sciences in Berlin, Germany were retrospectively analysed
      and interpreted, taking into account police investigations, autopsy results and
      toxicological analyses. RESULTS: In total, 22 cases with DA intoxications were
      discovered (?=16/?=6, age-at-death range 17 to 90years). Maximum blood
      concentration was measured at 77.5MUg/mL. Cause of death was due to DA
      intoxication in eight suicide cases; seven of those were combined intoxications
      (DA and other substances, particularly diphenhydramine). During the evaluated
      time period no monointoxications with DA were discovered. CONCLUSION: Benchmarks
      published in past literature are meant as orientation during evaluation of post
      mortem DA evidence. These should not be used as absolute values and need to be
      interpreted individually in each case. Post-mortem redistribution needs to be
      considered as a main factor in alteration of DA concentration measurement.
      Furthermore, proof of DA ingestion found in gastric content should only be
      interpreted quantitatively due to unreliable calculation of the ingested amount.
      In conclusion, a variety of factors, such as the time period between time of
      death and the time of the first toxicological analysis, the condition of the body
      and the findings at autopsy, must also be critically considered.

PMID- 24438780
TI  - A comparison of statistical models for the analysis of complex forensic DNA
      profiles.
AB  - Complex mixtures and LtDNA profiles are difficult to interpret. As yet there is
      no consensus within the forensic biology community as to how these profiles
      should be interpreted. This paper is a review of some of the current
      interpretation models, highlighting their weaknesses and strengths. It also
      discusses what a forensic biologist requires in an interpretation model and if
      this can be realistically executed under current justice systems. 

PMID- 24438781
TI  - Hyperspectral imaging of gel pen inks: an emerging tool in document analysis.
AB  - Hyperspectral imaging (HSI) is a useful technique in the examination of writing
      inks, including gel pen inks, which combines digital imaging with % reflectance
      spectroscopy. This facilitates the detection of subtle differences between
      chemically similar inks. This study analysed a variety of blue, red and black gel
      inks on white office paper using HSI. The potential of the technique for ink
      discrimination compared to other analytical methods of examination is
      highlighted. Discriminating powers of 1.00, 0.90 and 0.40 were achieved using HSI
      for red, blue and black gel inks respectively. The overall discriminating power
      of 0.76 for the technique combined with its non-destructive nature and minimal
      sampling requirements demonstrates promise for this type of application. 

PMID- 24438782
TI  - Effective use of forensic science in volume crime investigations: identifying
      recurring themes in the literature.
AB  - New scientific, technological and legal developments, particularly the
      introduction of national databases for DNA and fingerprints, have led to
      increased use of forensic science in the investigation of crime. There is an
      assumption, and in some instances specific assertions, that such developments
      bring improvements either in broad criminal justice terms or more narrowly in
      terms of economic or practical efficiencies. The underlying presumption is that
      the new technological opportunities will be understood and effectively
      implemented. This research investigates whether such increases in activity have
      also been accompanied by improvements in the effective use of forensic science. A
      systematic review of thirty-six reports published (predominantly in England and
      Wales) since the 1980s, which have considered the use of forensic science in the
      investigation of volume crimes, was carried out. These reports have identified a
      number of recurrent themes that influenced how effectively forensic science was
      used in investigations. The themes identified included forensic knowledge and
      training of investigators, communication and information exchange between
      specialists and investigators, timeliness of forensic results, interagency
      relationships and deployment of crime scene examiner resources. The research
      findings suggest that these factors continue to hinder the effective use of
      forensic science despite technological advances and this paper considers their
      potential causes. 

PMID- 24438783
TI  - The recovery of semen from bathwater using the Evidence Recovery System (ERS).
AB  - Sexual offences are under-reported and ascertaining accurate offence numbers is
      difficult. Any methods which could increase the ability to obtain biological
      evidence or reduce the additional distress associated with reporting a sexual
      offence may result in an increase in reporting this crime type. The Evidence
      Recovery System (ERS) is designed to collect trace evidence, including hairs,
      fibres and biological evidence, from bath or shower water in a non-invasive
      manner. Initially, samples of semen were placed in baths filled with water, and
      washing was simulated using a range of body wash products. The water was then
      drained through the ERS before its filters were subjected to acid phosphatase
      testing and haematoxylin and eosin staining of spermatozoa. Recovered spermatozoa
      were then graded accordingly. Following this, the experiment was repeated with
      the addition of dirt/dust particulates during the washing stage, to simulate
      recovery of biological evidence in a more realistic environment. The results
      showed that spermatozoa considered 'easy to find' could regularly be obtained
      from bathwater using the ERS. It appeared that this recovery was not affected by
      the presence of different body wash products. When dust/dirt particles were
      added, the number of spermatozoa recovered increased at two of the evidence
      collection stages. The difference in recovery was considered to be statistically
      significant. This study provides evidence to suggest the feasibility of use of
      the ERS as a method to collect semen evidence from individuals subjected to
      sexual offences. The recovery of spermatozoa does not appear to be affected by
      the presence of a body wash, but does appear to be improved when skin cells, hair
      and other debris are transferred into the water, as would be likely during a
      bath/shower. Further to this, the possibility of obtaining spermatozoa from the
      home bath or shower of a victim following a post-offence bathing experience is
      implied. 

PMID- 24438784
TI  - Report into a discordant result at D16S539 between SGM Plus(r) and PowerPlex(r)
      ESI 16 kits in a criminal case sample and implications for the UK National DNA
      Database upgrade.
AB  - Upon re-testing of a DNA extract as part of a defence examination, a discordant
      result was observed at D16S539. Further STR testing and DNA sequencing of the
      sample identified the cause as a primer binding site mutation which was shown to
      be a previously unreported SNP. The testing results obtained in this case are
      considered in light of the current ongoing Multiplex Upgrade Project in the UK
      and the likely increase in discordant results that may be observed once different
      next generation kits are introduced. 

PMID- 24438786
TI  - The Stuart Kind memorial lecture 2013.

PMID- 24438785
TI  - Characteristics of electrically injured skin from human hand tissue samples using
      Fourier transform infrared microspectroscopy.
AB  - This technical note describes a method for distinguishing normal skin tissue
      samples from those electrically injured by Fourier transform infrared
      microspectroscopy (FTIR MSP). Furthermore, the infrared spectral features of
      electrically injured cells and tissues were evaluated to identify molecular
      changes in epidermal cells. In the present study, 20 human hand tissue samples
      were evaluated macroscopically and histopathologically. The electrically injured
      skin samples were subdivided into 2 regions [normal cell regions (NCRs) and
      polarized cell regions (PCRs)] and 14 major spectral absorption bands were
      selected. The spectral results showed that the band absorbance at 1080, 1126,
      1172, 1242, 1307, 1403, 1456, 1541, 2852, 2925, 2957, 3075, and 3300cm(-1)
      increased significantly both in the stratum and non-stratum corneum of the PCRs
      in electrically injured skin tissues samples. No significant difference was found
      between normal skin and the NCR of the electrically injured skin samples. The
      band absorbance ratios of A1172/A1126, A1456/A1403, and A2925/A2957 were
      significantly increased, whereas the A1652/A1541 ratio was decreased in the PCR
      of the stratum corneum and non-stratum corneum. Baseline changes from 4000 to
      near 1737cm(-1) were observed in the spectra of the electrically injured skin
      samples, which were interpreted in terms of the pathological process involved in
      electrical injury. FTIR-MSP presents a useful method to provide objective
      spectral markers for the assisted diagnosis of electrical marks. 

PMID- 24438796
TI  - Embolization of dural arteriovenous fistula of the anterior cranial fossa through
      the middle meningeal artery with Onyx.
AB  - OBJECTIVE: Dural arteriovenous fistula (DAVF) of the anterior cranial fossa is
      usually treated by surgical disconnection or endovascular embolization via the
      ophthalmic artery. The middle meningeal artery is a rarely used approach. This
      study investigated the safety and efficacy of embolization of DAVF of the
      anterior cranial fossa with Onyx through the middle meningeal artery. METHODS: A
      retrospective review of a prospective cerebral vascular disease database was
      performed. Patients with DAVF of the anterior cranial fossa managed with
      embolization through the middle meningeal artery with Onyx were selected.
      Information on demography, symptoms and signs, angiographic examinations,
      interventional treatments, angiographic and clinical results, and follow-up was
      collected and analyzed. RESULTS: Five patients were included in this study, four
      of whom had hemorrhage. All fistulas were fed by the bilateral ethmoidal arteries
      arising from the ophthalmic artery and by the anterior branch of the middle
      meningeal artery. The abnormal shunt unilaterally drained into the superior
      sagittal sinus with interposition of the cortical veins all five patients. All
      endovascular treatments were successful with evidence of an angiographic cure. No
      complications occurred, and all patients recovered uneventfully without
      neurologic deficits. There were nearly no symptoms among the patients during
      follow-up. CONCLUSION: Embolization of DAVF of the anterior cranial fossa via the
      middle meningeal artery with Onyx is safe, effective, and a good choice for
      management of DAVF. More cases are needed to verify these findings.

PMID- 24438797
TI  - Efficacy, complications and clinical outcome of endovascular treatment for
      intracranial intradural arterial dissections.
AB  - OBJECTIVE: Intracranial intradural dissections are challenging to treat, and
      published data regarding treatment outcomes remains relatively limited. We
      retrospectively evaluated our experience with endovascular techniques in the
      treatment of intracranial intradural dissections, and describe the efficacy and
      clinical outcomes with treatment. METHODS: Between January 2003 and December
      2011, 23 patients with 23 intracranial intradural arterial dissections underwent
      endovascular treatment at our institution. Eighteen were treated with coil
      embolization (14 with parent vessel sacrifice, 4 with aneurysm coiling), 4 with
      flow diverting stents (Pipeline Embolization Device) and 1 with primary
      angioplasty and stenting. Treatment indications were subarachnoid hemorrhage
      (n=16), cerebral ischemia (n=2), headache (n=3), or elective (n=2). RESULTS: The
      peri-procedural complication rate was 17.4%, 3 of the 4 cases sustained no
      serious clinical sequelae. Four deaths unrelated to the procedure occurred in
      patients with subarachnoid hemorrhage. Angiographic follow-up demonstrated
      complete occlusion in 8 of 14 surviving cases treated by coil embolization,
      incomplete occlusion in 2 cases. Four cases were lost to follow-up, but all of
      these had complete occlusion post-procedure. Successful angiographic outcomes
      were seen at follow-up in patients treated with flow diverting stents and primary
      intracranial stenting. Clinical follow-up showed a mRS of 0-1 in 15 (78.9%) of 19
      patients, mRS of 2 in 1 patient, mRS of 3 in 1 patient and mRS of 5 in 1 patient.
      There was no neurological deterioration, re-bleeding or deaths during the follow
      up period. CONCLUSION: Intracranial arterial dissections, particularly those
      presenting with subarachnoid hemorrhage, are lesions associated with high
      mortality. They can be effectively managed endovascularly. In our experience,
      endovascular treatment can be associated with moderate peri-procedural risks.

PMID- 24438798
TI  - Atypical cerebral language dominance in a right-handed patient: An
      anatomoclinical study.
AB  - OBJECTIVE: Approximately 97% of the right-handers has left hemisphere language
      dominance. Within the language dominant hemisphere Broca's area is of crucial
      importance for a variety of linguistic functions. As a result, tumour resection
      in and around Broca's area is controversial. However, studies showed that by
      means of Direct Electrical Stimulation (DES) tumour resection in this region can
      be safely performed. We report unexpected anatomoclinical findings in a right
      handed patient who underwent tumour resection in the left prefrontal lobe.
      METHODS: Language functions in this right-handed patient were extensively
      examined in the pre-, intra-, and postoperative phase by means of a standardised
      battery of neurolinguistic and neurocognitive tests. Results obtained in the pre-
      and postoperative phase are compared. In addition, intraoperative DES findings
      and postoperative functional Magnetic Resonance Imaging (fMRI) and Diffusion
      Tensor Imaging (DTI) results are reported. RESULTS: Tumour resection near Broca's
      area was safely performed since no positive language sites were found during
      intraoperative DES. Since no linguistic deficits occurred in the pre-, intra-, or
      postoperative phase, atypical language dominance was suspected.
      Neuropsychological investigations, however, disclosed permanent executive
      dysfunction. Postoperative fMRI and DTI confirmed right cerebral language
      dominance as well as a crossed cerebro-cerebellar functional link with the left
      cerebellar hemisphere. DISCUSSION: Atypical right hemisphere language dominance
      in this right-handed patient is reflected by: (1) the total absence of language
      problems in the pre-, intra- and postoperative phase, (2) absence of positive
      stimulation sites during DES, (3) a clearly more pronounced arcuate fasciculus in
      the right cerebral hemisphere (DTI), (4) a crossed functional connection between
      the right cerebrum and the left cerebellum (fMRI). Two hypothetical explanations
      for the pattern of crossed cerebral language dominance are put forward: (1)
      preoperative brain plasticity mechanisms inducing a shift of language functions
      to the right hemisphere or (2) right hemisphere language dominance as a
      maturational variant. This case with atypical cerebral language dominance shows
      that although DES is the 'gold standard' to identify eloquent language regions
      and their pathways, fMRI and DTI are important adjuncts to guide surgery, to
      identify language lateralisation and to study anatomoclinical correlations.

PMID- 24438799
TI  - Endovascular treatment of dural arteriovenous fistulas using dual lumen balloon
      microcatheter: technical aspects and results.
AB  - OBJECTIVE: We report our results of our experience using transarterial balloon
      assisted embolization of aggressive DAVFs using a dual lumen balloon
      microcatheter. The advantages and disadvantages of this technique when compared
      to different Onyx embolization techniques are discussed. PATIENTS AND METHODS:
      All patients with aggressive DAVFs who were treated with Onyx using transarterial
      balloon-assisted technique with a dual lumen balloon microcatheter were included.
      Clinical presentation, location of DAVF, Borden type, dual lumen balloon
      microcatheter used, amount of Onyx used, Onyx injection duration, complications,
      immediate angiographic and follow up results were included in the analysis.
      RESULTS: Five patients fulfilled the selection criteria. Their ages ranged from
      24 to 62 years old. In 4 cases the dual lumen balloon microcatheter was a Scepter
      C 4mm*10mm (Microvention, Tustin, CA); in the other patient the device used was
      an Ascent 4mm*10mm (Codman, Raynham, MA). In all 5 patients the dual lumen
      balloon microcatheter was used with the objective to cure the lesion and it was
      successful in all 5 cases. There was no vessel injury, unwanted embolization,
      retained microcather, microcatheter rupture or cranial nerve deficits in our
      series. Our mean Onyx injection time was 6.4min (range from 2 to 10min). There
      were no procedural complications in our series. Four out of 5 patients had
      angiographic follow up demonstrating persistent angiographic cure (follow up mean
      6 months - range 4-7 months). CONCLUSIONS: Our experience in this small series of
      patients indicates that the use of dual lumen balloon microcatheters is safe and
      feasible, facilitating the use of Onyx for embolization of DAVFs.

PMID- 24438800
TI  - Unilateral versus bilateral pedicle screw fixation in lumbar interbody fusion: a
      meta-analysis of complication and fusion rate.
AB  - Unilateral or bilateral pedicle screw (PS) fixation in lumbar interbody fusion
      remains controversial. The aim of this study was to evaluate the complication and
      fusion rate for both surgical techniques based on published studies. Pubmed,
      Cochrane Library and Embase Databases were searched to identify studies reporting
      complication rate or fusion rate of unilateral and bilateral PS fixation in
      lumbar interbody fusion. Outcomes of complication rate and fusion rate were
      analyzed. Seven articles including 501 patients were identified fitting inclusion
      criteria. There was no significant difference of total complication rate (RR
      1.17, 95% CI: 0.73-1.89, P=0.51) and fusion rate (RR 0.94, 95% CI: 0.87-1.01,
      P=0.07) between the two groups. However, the fusion cage migration rate was
      significant higher (RR 2.41, 95% CI: 1.06-5.46, P=0.04) in unilateral group than
      bilateral group. In conclusion, the available evidence indicated that both
      unilateral PS fixation and bilateral PS fixation could get satisfactory fusion
      rate and complication rate. But unilateral PS fixation had more fusion cage
      migration than bilateral PS fixation in patients who undergo lumbar interbody
      fusion. 

PMID- 24438801
TI  - Foot drop resulting from degenerative lumbar spinal diseases: clinical
      characteristics and prognosis.
AB  - Foot drop is a condition that can substantially add to the disability of patients
      with degenerative lumbar spinal disorders. The most common degenerative
      conditions associated with foot drop are lumbar disc herniation and lumbar spinal
      stenosis. The level most commonly affected is the L4/5 spinal level. Most
      patients are treated with surgery, although there is insufficient evidence to
      support that surgery is superior to conservative therapy. In most surgical
      patients, foot dorsiflexion will improve to some degree. The preoperative power
      of foot dorsiflexion is the key factor associated with prognosis. 

PMID- 24438802
TI  - Intracranial, intra-axial metastatic giant cell tumor of bone: case report and
      review of literature.

PMID- 24438803
TI  - Treatment of aneurysmal subarachnoid hemorrhage in young patients.

PMID- 24438804
TI  - Predictive value of fractional anisotropy of the arcuate fasciculus for the
      functional recovery of language after brain tumor resection: a preliminary study.
AB  - OBJECTIVE: The arcuate fasciculus has been recognized as an important pathway for
      language processing. Brain tumors located in proximity to the fasciculus
      frequently cause preoperative language impairment, and in some cases, no language
      recovery occurs after tumor resection. No predictive value has been presented for
      possible postoperative language recovery after tumor resection. The aim of this
      study is to analyze the preoperative state of the arcuate fasciculus in the
      patients with brain tumor from the perspective of its usefulness as a predictive
      factor for postoperative recovery of language functions. METHODS: For 12 right
      handed patients with brain tumors in the left hemisphere, preoperative arcuate
      fasciculi were analyzed with fractional anisotropy (FA) of the diffusion tensor
      imaging (DTI) tractography. Language functions were evaluated pre- and
      postoperatively by using the Western Aphasia Battery (WAB). The preoperative
      value of the FA of the arcuate fasciculus on the lesion side was examined in
      relation with the language recovery. RESULTS: There was a positive relationship
      between preoperative increasing values of the FA of the left arcuate fasciculus
      and improvement of the postoperative total WAB score (p=0.0056), and the scores
      of the naming (p=0.018), reading (p=0.029), and writing subcategories (p=0.012)
      CONCLUSION: The preoperative increasing value of the FA of the arcuate fasciculus
      in the dominant hemisphere could be a predictor for postoperative language
      recovery following tumor resection. Meticulous procedure should be performed
      especially in the cases with higher FA of the arcuate fasciculus harboring high
      possibility of language recovery.

PMID- 24438805
TI  - Isolated transient myoclonus in the elderly: an under-recognized condition?
AB  - BACKGROUND: Cases of transient myoclonus without other neurological
      manifestations in the elderly have very rarely been reported. OBJECTIVE: To
      report clinical features of elderly people with isolated transient myoclonus.
      METHODS: Clinical and laboratory features of 11 consecutive patients with
      isolated transient myoclonus (six men and five women; mean age, 75 years) were
      reviewed. Transient myoclonus was defined as an acute onset of tremulous
      myoclonus with/without asterixis in adults without other neurological symptoms.
      RESULTS: Preceding infections were recorded in five patients (pneumonia, two;
      upper respiratory tract infection, two; and septic arthritis of the shoulder,
      one). Myoclonus predominantly affected the head and/or neck (n=10) and upper
      extremities (n=11), compared with the trunk (n=2) and lower extremities (n=6).
      Asterixis was observed in six patients. Laboratory testing, neuroimaging, and
      electroencephalograms revealed no specific abnormalities. With or without
      treatment using benzodiazepines, myoclonus in all patients resolved completely
      within 1-4 days, although five had recurrence 2-19 months after their first
      episodes. Among these five patients, the accompanying asterixis patterns
      (presence or not) in four were different in the first and subsequent episodes.
      CONCLUSIONS: Isolated transient myoclonus with or without asterixis may be more
      common than generally believed, and it could be a clinical entity or disease
      spectrum. Transient myoclonus is a benign condition in the elderly, but can be
      under-reported or misdiagnosed. Therefore, it is important to recognize that the
      elderly may have this syndrome.

PMID- 24438806
TI  - Intraventricular neurocytomas: a systematic review of stereotactic radiosurgery
      and fractionated conventional radiotherapy for residual or recurrent tumors.
AB  - To determine optimal treatment for recurrent or residual intraventricular
      neurocytomas (IVNs), a systematic review of PubMed and EMBASE was conducted
      comparing fractionated conventional radiotherapy (FCRT) versus stereotactic
      radiosurgery (SRS). Inclusion criteria included histological IVN documentation,
      at least 6 months of follow-up observation and described dose of FCRT or SRS
      administered. Descriptive statistical and Kaplan-Meier analyses were performed.
      The literature search yielded 451 articles. Sixteen studies met inclusion
      criteria. The local tumor control proportion was 93% and 88% in the SRS and FCRT
      subgroups, respectively. The relative risk (RR) of local recurrence was 0.57 less
      (95% CI: 0.21-1.57; log-rank p=0.85) and the RR of all-cause mortality was 0.23
      less (95% CI: 0.05-1.05; log-rank p=0.22) in SRS subgroup compared to the FCRT
      subgroup but did not reach statistical significance. Recurrence was significantly
      associated with presence of histological atypia (log-rank p<0.001). Severe
      complications were lower in SRS subgroup (5.5% versus 7.5%, p=0.74); however,
      distant tumor recurrence was slightly lower in the FCRT subgroup (1.5% versus
      5.5%, p=0.24). The role of SRS or FCRT in the management of residual or recurrent
      IVNs will continue to depend on the balance between the risks and benefits of SRS
      and FCRT until better quality data are available. 

PMID- 24438807
TI  - A case of retroperitoneum-originated paraganglioma with multiple intracranial and
      bony metastases.

PMID- 24438808
TI  - Lymphatic malformation of the tongue with coexisting intractable epilepsy treated
      with corpus callosotomy: a case report.

PMID- 24438810
TI  - Anatomico-radiologic study of the distribution of the suboccipital artery of
      Salmon.
AB  - OBJECTIVES: The frequency of suboccipital injections to treat headaches has
      increased. The third segment of the vertebral artery is located in the
      suboccipital triangle and its main muscular branch, the suboccipital artery of
      Salmon (SAS), supplies blood to the suboccipital muscles. The purpose of this
      study was to radiographically investigate the morphology and territory of
      distribution of SAS. PATIENTS AND METHODS: Computed tomography angiographs of
      brains of 50 subjects (25 female, 25 men, mean age 70.2 years) were analyzed.
      RESULTS: SAS was present in 48% of subjects. The vessel was present bilaterally
      in 37.1%, and had a mean (SD) luminal diameter of 1.71 (0.34)mm and mean (SD)
      length of 36.42 (17.1)mm. SAS was found to have two morphologic patterns: (1) a
      single main trunk with collateral branches (52.6%) and (2) a short common trunk
      that divided into two branches (48.4%). The SAS supplied the obliquus capitis
      inferior, semispinalis capitis, and splenius capitis muscles. When the SAS was
      absent, the suboccipital muscles were supplied by a branch of the occipital
      artery. No anastomoses were found between the SAS and occipital artery.
      CONCLUSION: The suboccipital muscles are vascularized by the SAS and occipital
      artery. The detailed course of the SAS is important for clinicians and surgeons
      who perform procedures in the suboccipital region.

PMID- 24438809
TI  - Surgical outcomes of craniocervial junction meningiomas: a series of 22
      consecutive patients.
AB  - OBJECTIVE: We present our experience in managing craniocervical junction
      meningiomas and discuss various surgical approaches and outcomes. METHODS: We
      retrospectively reviewed 22 consecutive cases of craniocervical junction
      meningiomas operated on between August 1995 and May 2012. RESULTS: There were 15
      female and 7 male patients (mean age: 54 years). Meningiomas were classified
      based on origin as spinocranial (7 cases) or craniospinal (15 cases).
      Additionally, the tumors were divided into anatomical location relative to the
      brainstem or spinal cord: there were 2 anterior tumors, 7 anterolateral, 12
      lateral, and 1 posterolateral. Surgical approaches included the posterior midline
      suboccipital approach (9 cases), the far lateral approach (12 cases) and the
      lateral retrosigmoid approach (1 case). Gross-total resection was achieved in 45%
      of patients and subtotal in 55%. The most common post-operative complications
      were cranial nerve (CN) IX and X deficits. The mortality rate was 4.5%. There
      have been no recurrences to date with a mean follow-up was 46.5 months and the
      mean Karnofsky score at the last follow-up of 82.3. In this series, spinocranial
      tumors were detected at a smaller size (p=0.0724) and treated earlier (p=0.1398)
      than craniospinal tumors. They were associated with a higher rate of total
      resection (p=0.0007), fewer post-operative CN IX or X deficits (p=0.0053), and
      shorter hospitalizations (p=0.08). CONCLUSION: Our experience suggests that
      posterior midline suboccipital or far-lateral approaches with minimal condylar
      drilling and vertebral artery mobilization were suitable for most cases in this
      series.

PMID- 24438811
TI  - Cervical spondylodiscitis--a clinical analysis of surgically treated patients and
      review of the literature.
AB  - OBJECTIVE: The aim of this study was to analyze our clinical and neurological
      results of surgically treated patients suffering from cervical spondylodiscitis
      with focusing particularly on the surgical methods used and to review the
      literature. PATIENTS AND METHODS: We present a series of 21 patients operated
      with cervical spondylodiscitis between 1998 and 2011. Basic demographic data,
      comorbidities, the radiological segments involved, the surgical strategy with
      special consideration of the material used and the clinical outcome were
      evaluated retrospectively. RESULTS: The mean age of 6 female and 12 male patients
      was 65 years (range 28-89 years). The mean follow-up was 3.7 years ranging
      between 4 weeks and 9 years. The leading symptom was neurological deficits rather
      than pain. The segments C 5/6 (n=8) and C 6/7 (n=7) were most frequently
      involved. Different surgical methods depending on the location, anatomical and
      pathological condition and extension of the lesion were performed. CONCLUSION: In
      conclusion, cervical spondylodiscitis could effectively be treated in the
      presented patient cohort by surgical decompression, debridement and PMMA or bone
      graft implants followed by long term antibiotic therapy. The presented surgical
      reconstruction technique with PMMA might be a feasible alternative to the use of
      bone graft or cages. The promising clinical results warrant future prospective
      studies to further investigate this technique.

PMID- 24438812
TI  - Long term outcome in surgically treated posterior fossa epidermoids.
AB  - OBJECTIVES: To study posterior fossa epidermoids treated surgically at our
      institute and to compare their long term outcome with respect to extent of
      surgical decompression. MATERIALS AND METHODS: Retrospective analysis of 50 cases
      of posterior fossa epidermoid surgically treated at our institute between 1997
      and 2007. RESULTS: The mean duration from onset of symptoms to surgery was 2.5
      years. Patients with cerebellopontine angle (CPA) epidermoids presented
      predominantly with trigeminal neuralgia (35%) and hearing loss (29%) while
      patients with fourth ventricle epidermoids had features of raised intracranial
      pressure (ICP) and gait ataxia (69.2% each). The rate of recurrence was 9% in
      tumors considered totally removed and 93% in those subtotally removed. Of the 17
      patients with recurrences, 3 (7.9%) underwent a second operation. The mean
      duration of follow up at first recurrence was 9.3 years. CONCLUSION: Based on our
      experience, the rate of recurrence is significantly higher after subtotal removal
      as compared to total removal of epidermoids on long-term follow up. Symptomatic
      recurrence requiring re-exploration is evident only after a long duration (~10.9
      year) following primary surgery. Hence, total removal without producing new
      neurological deficits should be the standard goal when operating on posterior
      fossa epidermoid cysts.

PMID- 24438813
TI  - The perioperative management of antiplatelet agents for chronic subdural
      hematoma.

PMID- 24438814
TI  - Microvascular decompression of the eighth cranial nerve for unilateral pulsatile
      tinnitus.

PMID- 24438815
TI  - Trigeminal neuralgia pain relief after gamma knife stereotactic radiosurgery.
AB  - OBJECTIVES: To report outcomes of patients with medical and/or surgical
      refractory trigeminal neuralgia (TN) treated with gamma knife stereotactic
      radiosurgery (GK SRS). METHODS: One hundred and forty-nine patients with 152
      cases of TN treated with GK SRS were analyzed. All patients, except one, received
      a dose of 40Gy to the 50% isodose volume. The Barrow Neurological Institute (BNI)
      pain intensity score was used to grade pain. Actuarial rates of pain relief were
      calculated. Multiple factors were analyzed for association with pain relief.
      RESULTS: The median follow up was 27 months (4-71 months). Overall 92% of cases
      achieved a BNI score I-III after GK SRS. Of those who had pain relief after GK
      SRS, 32% developed pain recurrence defined as a BNI score of IV or V. The
      actuarial rate of freedom from pain recurrence (BNI scores I-III) of all treated
      cases at 1, 2 and 3-years was 76%, 69% and 60%, respectively. On univariate
      analysis age >=70 was predictive of better pain relief (p=0.046). Type of pain,
      prior surgery, multiple sclerosis, number of isocenters, treated nerve length,
      volume and thickness and distance from the root entry zone to the isocenter were
      not significant for maintaining a BNI score of I-III. Those who achieved a BNI
      score of I or II were more likely to maintain pain relief compared to those who
      only achieved a BNI score of III (93% vs 38% at three years, p<0.01). The rate of
      pain relief of twenty-seven patients who underwent repeat GK SRS was 70% and 62%
      at 1 and 2 years, respectively. Toxicity after first GK SRS was minimal with 25%
      of cases experiencing only new or worsening post-treatment numbness. CONCLUSION:
      GK SRS provides acceptable pain relief with limited morbidity in patients with
      medical and/or surgical refractory TN.

PMID- 24438816
TI  - Impaired diagnosis and successful management of a rare intra-axial central
      nervous system plasmacytoma in a patient with multiple myeloma.

PMID- 24438817
TI  - Successful endoscopic endonasal management of a transclival cerebrospinal fluid
      fistula secondary to ecchordosis physaliphora--an ectopic remnant of primitive
      notochord tissue in the clivus.

PMID- 24438818
TI  - 68Ga-DOTA-NGR as a novel molecular probe for APN-positive tumor imaging using
      MicroPET.
AB  - Aminopeptidase N (APN) is selectively expressed on many tumors and the
      endothelium of tumor neovasculature, and may serve as a promising target for
      cancer diagnosis and therapy. Asparagine-glycine-arginine (NGR) peptides have
      been shown to bind specifically to the APN receptor and have served as vehicles
      for the delivery of various therapeutic drugs in previous studies. The purpose of
      this study was to synthesize and evaluate the efficacy of a (68)Ga-labeled NGR
      peptide as a new molecular probe that binds to APN. METHODS: NGR peptide was
      conjugated with 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid
      (DOTA) and labeled with (68)Ga at 95 degrees C for 10 min. In vitro uptake and
      binding analysis was performed with A549 and MDA-MB231 cells. Biodistribution of
      (68)Ga-DOTA-NGR was determined in normal mice by dissection method. (68)Ga-DOTA
      NGR PET was performed in A549 and MDA-MB231 xenografts, and included dynamic and
      static imaging. APN expression in tumors and new vasculatures was analyzed by
      immunohistochemistry. RESULTS: The radiochemical purity of (68)Ga-DOTA-NGR was
      98.0% +/- 1.4% with a specific activity of about 17.49 MBq/nmol. The uptake of
      (68)Ga-DOTA-NGR in A549 cells increased with longer incubation times, and could
      be blocked by cold DOTA-NGR, while no specific uptake was found in MDA-MB231
      cells. In vivo biodistribution studies showed that (68)Ga-DOTA-NGR was mainly
      excreted from the kidney, and rapidly cleared from blood and nonspecific organs.
      MicroPET imaging showed that high focal accumulation had occurred in the tumor
      site at 1 h post-injection (pi) in A549 tumor xenografts. A significant reduction
      of tumor uptake was observed following coinjection with a blocking dose of DOTA
      NGR, whereas only mild uptake was found in MDA-MB231 tumor xenografts. Tumor
      uptake, measured as the tumor/lung ratio, increased with time peaking at 12.58 +/
      1.26 at 1.5 h pi. Immunohistochemical staining confirmed that APN was
      overexpressed on A549 cells and neovasculature. CONCLUSIONS: (68)Ga-DOTA-NGR was
      easily synthesized and showed favorable biodistribution and kinetics. (68)Ga-DOTA
      NGR could also specifically bind to the APN receptor in vitro and in vivo, and
      might be a potential molecular probe for the noninvasive detection of APN
      positive tumors and neovasculature.

PMID- 24438820
TI  - Do high rates of empirical treatment undermine the potential effect of new
      diagnostic tests for tuberculosis in high-burden settings?
AB  - In tuberculosis-endemic settings, patients are often treated empirically, meaning
      that they are placed on treatment based on clinical symptoms or tests that do not
      provide a microbiological diagnosis (eg, chest radiography). New tests for
      tuberculosis, such as the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA), are
      being implemented at substantial cost. To inform policy and rationally drive
      implementation, data are needed for how these tests affect morbidity, mortality,
      transmission, and population-level tuberculosis burden. If people diagnosed by
      use of new diagnostics would have received empirical treatment a few days later
      anyway, then the incremental benefit might be small. Will new diagnostics
      substantially improve outcomes and disease burden, or simply displace empirical
      treatment? Will the extent and accuracy of empirical treatment change with the
      introduction of a new test? In this Personal View, we review emerging data for
      how empirical treatment is frequently same-day, and might still be the
      predominant form of treatment in high-burden settings, even after Xpert
      implementation; and how Xpert might displace so-called true-positive, rather than
      false-positive, empirical treatment. We suggest types of studies needed to
      accurately assess the effect of new tuberculosis tests and the role of empirical
      treatment in real-world settings. Until such questions can be addressed, and
      empirical treatment is appropriately characterised, we postulate that the
      estimated population-level effect of new tests such as Xpert might be
      substantially overestimated. 

PMID- 24438819
TI  - Year in review 2012: Critical Care--management.
AB  - Outcomes research plays a key role in defining the effects of medical care in
      critical care. Last year Critical Care published a number of papers that
      evaluated patient-centered and policy-relevant outcomes. We present this review
      article focusing on key reported outcomes associated with severe community
      acquired pneumonia, mortality associated with decisions regarding triage to the
      ICU, and both short-term and long-term mortality associated with ICU admissions.
      We further analyze the literature, assessing outcomes such as quality of life and
      the psychological burden associated with critical care. We also reviewed
      processes of care, and studies looking at cost analysis of treatment associated
      with critical care. 

PMID- 24438821
TI  - Adaptation and evaluation of the GrazeIn model of grass dry matter intake and
      milk yield prediction for grazing dairy cows.
AB  - The prediction of grass dry matter intake (GDMI) and milk yield (MY) are
      important to aid sward and grazing management decision making. Previous
      evaluations of the GrazeIn model identified weaknesses in the prediction of GDMI
      and MY for grazing dairy cows. To increase the accuracy of GDMI and MY
      prediction, GrazeIn was adapted, and then re-evaluated, using a data set of 3960
      individual cow measurements. The adaptation process was completed in four
      additive steps with different components of the model reparameterised or altered.
      These components were: (1) intake capacity (IC) that was increased by 5% to
      reduce a general GDMI underprediction. This resulted in a correction of the GDMI
      mean and a lower relative prediction error (RPE) for the total data set, and at
      all stages of lactation, compared with the original model; (2) body fat reserve
      (BFR) deposition from 84 days in milk to next calving that was included in the
      model. This partitioned some energy to BFR deposition after body condition score
      nadir had been reached. This reduced total energy available for milk production,
      reducing the overprediction of MY and reducing RPE for MY in mid and late
      lactation, compared with the previous step. There was no effect on predicted
      GDMI; (3) The potential milk curve was reparameterised by optimising the rate of
      decrease in the theoretical hormone related to secretory cell differentiation and
      the basal rate of secretory cell death to achieve the lowest possible mean
      prediction error (MPE) for MY. This resulted in a reduction in the RPE for MY and
      an increase in the RPE for GDMI in all stages of lactation compared with the
      previous step; and (4) finally, IC was optimised, for GDMI, to achieve the lowest
      possible MPE. This resulted in an IC correction coefficient of 1.11. This
      increased the RPE for MY but decreased the RPE for GDMI compared with the
      previous step. Compared with the original model, modifying this combination of
      four model components improved the prediction accuracy of MY, particularly in
      late lactation with a decrease in RPE from 27.8% in the original model to 22.1%
      in the adapted model. However, testing of the adapted model using an independent
      data set would be beneficial and necessary to make definitive conclusions on
      improved predictions.

PMID- 24438822
TI  - Primary ciliary dyskinesia assessment by means of optical flow analysis of phase
      contrast microscopy images.
AB  - Primary ciliary dyskinesia implies cilia with defective or total absence of
      motility, which may result in sinusitis, chronic bronchitis, bronchiectasis and
      male infertility. Diagnosis can be difficult and is based on an abnormal ciliary
      beat frequency (CBF) and beat pattern. In this paper, we present a method to
      determine CBF of isolated cells through the analysis of phase-contrast microscopy
      images, estimating cilia motion by means of an optical flow algorithm. After
      having analyzed 28 image sequences (14 with a normal beat pattern and 14 with a
      dyskinetic pattern), the normal group presented a CBF of 5.2 +/- 1.6 Hz, while
      the dyskinetic patients presented a 1.9 +/- 0.9 Hz CBF. The cutoff value to
      classify a dyskinetic specimen was set to 3.45 Hz (sensitivity 0.86, specificity
      0.93). The presented methodology has provided excellent results to objectively
      diagnose PCD.

PMID- 24438823
TI  - Metal release from ceramic coatings for dental implants.
AB  - OBJECTIVES: Two types of ceramic coatings on commercially pure titanium for
      dental implant applications with different Ca/P ratios in the range from 1.5 to
      4.0, and two different thicknesses (~5 and ~15MUm) were examined with the aim of
      underpinning the effect of coating composition, thickness and microstructure on
      the corrosion behavior and hydroxyapatite forming ability in SBF. METHODS:
      Bioactive coatings were formed on Ti by plasma electrolytic oxidation (PEO). The
      composition, structure, and morphology of the materials were characterized before
      and after the immersion in simulated body fluid solution (SBF) at 37 degrees C
      for up to 4 weeks. All the materials were screened with respect to metal ion
      release into SBF. RESULTS: Only thick PEO coating with overstoichiometric Ca/P
      ratio of 4.0 exhibited capacity to induce the precipitation of hydroxyapatite
      over the short period of 1 week. Long term Ti(4+) ion release from all PEO-coated
      materials was 2-3 times lower than from the uncoated Ti. Metal ion release is
      attributed mostly to chemical dissolution of the coating at initial stages of
      immersion. SIGNIFICANCE: The long term stability was greater for thin PEO coating
      with overstoichiometric Ca/P ratio of 2.0, which exhibited ~95ngcm(-2) of Ti(4+)
      ions release over 4 weeks. Thin PEO coatings present economically more viable
      option.

PMID- 24438824
TI  - Short-term efficacy of the IL6 receptor antibody tocilizumab in patients with HIV
      associated multicentric Castleman disease: report of two cases.
AB  - Multicentric Castleman disease (MCD) is a lymphoproliferative disorder caused by
      human herpesvirus 8 (HHV8) infection HIV associated MCD (HIV-MCD) presents with
      various clinical symptoms. Many HIV-negative MCD patients are often treated with
      anti-human interleukin-6 (IL6) receptor monoclonal antibodies (tocilizumab), and
      successful results have been reported. IL-6 plays an important role in the
      development of both HIV-positive and HIV-negative MCD; however, the efficacy of
      tocilizumab in HIV-MCD patients is unknown. We herein report the clinical and
      biologic courses of two HIV-MCD patients treated with tocilizumab. In both cases,
      a significant and rapid clinical improvement was observed after the first
      infusion. However, the treatment efficacy was not maintained for a long period,
      and relapse occurred at 15 and 22 weeks, respectively. Both patients received
      rituximab and subsequently achieved complete clinical remission. Our report, in
      addition to data presented in the literature, suggests that tocilizumab could be
      an initial treatment option in patients with HIV-MCD. 

PMID- 24438825
TI  - Families of choice and noncollegiate sororities and fraternities among lesbian
      and bisexual African-American women in a southern community: implications for
      sexual and reproductive health research.
AB  - Background Self-identified lesbian and bisexual African-American women living in
      the southern United States are a relatively hidden subpopulation within the
      lesbian, gay, bisexual and transgender (LGBT) community. Existing research
      suggests that African-American lesbian and bisexual women are at high risk for
      sexually transmissible infections (STIs), but the sexual and reproductive health
      needs of this population are just beginning to be understood. METHODS: We
      conducted four focus groups and five individual interviews with 24 lesbian and
      bisexual African-American women living in the Jackson, Mississippi, metropolitan
      area, recruited through the local STI clinic and through word of mouth. We aimed
      to characterise the role of two types of social organisations (lesbian families
      and noncollegiate lesbian sororities and fraternities) among the local LGBT
      community, and their influence on the sexual health of their members. RESULTS:
      Both types of social organisations serve positive functions for their members.
      Lesbian families provide support and stability; this appears beneficial for
      younger individuals, who may lack support from biological families. Lesbian
      sororities and fraternities are visible due to their emphasis on community
      service, and offer a strong sense of solidarity and belonging. In both
      organisation types, discussions about sex were common, although members
      acknowledged a lack of information regarding safer sex among lesbian and bisexual
      women. CONCLUSIONS: Existing social organisations within the LGBT community, such
      as lesbian families and lesbian sororities and fraternities, should be
      incorporated into community-based popular opinion leader or lay heath advisor
      interventions in an effort to meet the sexual and reproductive health needs of
      marginalised populations.

PMID- 24438827
TI  - Early trauma induced coagulopathy (ETIC): prevalence across the injury spectrum.
AB  - INTRODUCTION: Newer studies have hypothesised about a coagulopathy that occurs
      early after trauma, early trauma induced coagulopathy, ETIC, and is defined by an
      elevated admission prothrombin time (PT). Also, referred to by some authors as
      acute traumatic coagulopathy, it has been most often studied in cohorts of
      severely injured or hypotensive patients. However, we wanted to prospectively
      investigate ETIC in a large all-comers cohort to confirm its prevalence across
      the entire spectrum of injury, to evaluate its risk pattern and to determine a
      possible relationship to reduced survival. METHODS: We conducted a prospective
      cohort study at a Level I trauma centre from July 15, 2008 to November 15, 2009.
      Demographics, injury mechanism, time from injury and to hospital arrival, fluid
      and blood administration and vital signs were collected at hospital arrival and
      to the time of first blood sample collection for all patients admitted for 24h or
      longer. Our primary outcome was the incidence of mortality by the 28th hospital
      day, referred to as 28 day in-hospital mortality. RESULTS: 701 patients were
      included in the final study cohort. There was 75.3% male, 25.7% penetrating, with
      a mean age of 39 years. The overall mortality was 7.3%. ETIC occurred in 114
      patients (16.3%) and was found to be independently associated with death (odds of
      death (per 0.10s increase in PT): 1.10, p=0.001). ETIC patients, as a group, were
      more severely injured, had more hypotension and head injury and used more
      crystalloid and blood products than non-ETIC patients. However, even mildly
      injured patients, who had an ISS<16, normal RTS score, and no fluid
      resuscitation, had an ETIC prevalence of 11.7% (11/94). CONCLUSIONS: ETIC is an
      early, primary post-injury coagulopathy that occurs in 16.3% of admitted trauma
      patients. It is associated with an increase in mortality, even when controlling
      for crystalloids, vital signs, injury severity and head injury. It can also be
      found in approximately 11% of mildly injured patients (patients without
      physiological derangement or blood product administration). Therefore, further
      elucidation of ETIC is strategic to impacting trauma patient outcome.

PMID- 24438831
TI  - Accurate measurements of the true column efficiency and of the instrument band
      broadening contributions in the presence of a chromatographic column.
AB  - A rapid and simple validated experimental protocol is proposed for the accurate
      determination of the true intrinsic column efficiency and for that of the
      variance of the extra-column volume of the instrument used, the latter being
      obtained without requiring the removal of the chromatographic column from the
      HPLC system. This protocol was applied to 2.1mm*100mm columns packed with sub-3
      (2.7MUm Halo Peptide ES-C18) and sub-2MUm (1.6MUm prototype) core-shell
      particles. It was validated by observing the linear behavior of the plot of the
      apparent column plate height versus the reciprocal of (1+k')(2) for at least
      three homologous compounds, with a linear regression coefficient R(2) larger than
      0.999. Irrespective of the contribution of the several, different instruments
      used to the total band broadening, the same column HETP value was obtained within
      5%. This new protocol outperform the classical one in which the chromatographic
      column is replaced with a zero dead volume (ZDV) union connector to measure the
      extra-column volume variance, which is subtracted from the variance measured with
      the column to measure the intrinsic HETP. This protocol fails because it
      significantly underestimates the system volume variance. 

PMID- 24438832
TI  - Ion-pair reversed-phase liquid chromatography-quadrupole-time-of-flight and
      triple-quadrupole-mass spectrometry determination of ethyl sulfate in wastewater
      for alcohol consumption tracing.
AB  - Ethyl sulfate (EtS) is excreted in urine as a minor metabolite (0.010-0.016% on
      molar basis) after intake of alcoholic beverages, being a convenient biomarker
      for ethanol tracing after its determination in sewage. In this work, a new method
      for the direct determination of EtS in wastewater by liquid chromatography
      (tandem) mass spectrometry (LC-MS(/MS)) has been developed. Different LC columns,
      mobile phases, and detection systems have been tested. Convenient retention by
      ion-pair reversed-phase LC was achieved by addition of 50mM tetrabutylamonium
      bromide to the sample. Also, a triple-quadrupole (QqQ) instrument and a
      quadrupole time-of-flight (QTOF) system were compared. The repeatability of both
      systems and linearity was comparable, with RSD<=10% in sewage samples. The QqQ
      instrument provided a better limit of detection (LOD=0.1MUgL(-1)) than the QTOF
      system LOD (0.2MUgL(-1)). However, the LOD of this last instrument was still good
      enough for wastewater concentrations, while avoiding problems with interferences
      on the QqQ not permitting positive identification with this last system. The
      stability of EtS was tested and it has proven to be stable in wastewater for at
      least one week at room temperature and more than one month at -20 degrees C. The
      application of the method to samples collected during a week in a Galician (NW
      Spain) city showed EtS concentrations between 4 and 12MUgL(-1). This translated
      into a per capita consumption of pure ethanol in the range from 9 to 24mLday(
      1)inh(-1), observing an increase during the weekend compared to weekdays. 

PMID- 24438833
TI  - Low-picomolar analysis of peptides by on-line coupling of fritless solid-phase
      extraction to sheathless capillary electrophoresis-mass spectrometry.
AB  - A novel fritless solid-phase extraction (SPE) microcartridge was designed for
      combination with sheathless capillary electrophoresis-mass spectrometry
      (sheathless CE-MS) employing a prototype porous-tip capillary for
      nanoelectrospray ionization (nanoESI). The inlet of the separation capillary
      (30MUm inner diameter (id), 150MUm outer diameter (od)) was inserted in a 4mm
      long SPE microcartridge (150MUm id, 365MUm od) packed with a C18 sorbent of 55
      105MUm particle size. Performance of the SPE-CE-MS system was evaluated using
      diluted solutions of the three opioid peptides dynorphin A (1-7) (DynA),
      endomorphin 1 (End1) and met-enkephalin (Met). Sample volumes of 1.5MUL were
      loaded on the SPE microcartridge and the retained peptides were eluted with 22nL
      of an acidic methanol/water (60:40, v/v) solution. Using a pressure of 50mbar
      during separation to speed up the analysis, good peptide resolution was obtained
      with acceptable plate numbers (between 53,000 and 92,000). Intraday relative
      standard deviations (% RSD) for peptide migration times and peak areas were below
      4% and 9%, respectively. The SPE-CE-MS method showed good linearity in the 0.05
      5ngmL(-1) range and limits of detection (LODs) were 10pgmL(-1). However, loading
      a larger volume of sample (8MUL), LODs could be decreased down to 2pgmL(-1) (2.2
      3.5pM). This represents an improvement of up to 5000-fold with respect to the
      LODs achieved by sheathless CE-MS without on-line preconcentration demonstrating
      the potential of on-line SPE for further enhancing sensitivity. 

PMID- 24438834
TI  - Phenolic profile evolution of different ready-to-eat baby-leaf vegetables during
      storage.
AB  - Ready-to-eat baby-leaf vegetables market has been growing and offering to
      consumers convenient, healthy and appealing products, which may contain
      interesting bioactive compounds. In this work, the composition and the evolution
      of the phenolic compounds from different baby-leaf vegetables during refrigerated
      storage was studied. The phenolic compounds were extracted using pressurized
      liquid extraction (PLE) and the phenolic profile of each sample was analyzed and
      quantified by using LC-MS and LC-DAD methods, respectively, at the beginning and
      at the end of a 10-day storage period. The baby-leaf vegetables studied included
      green lettuce, ruby red lettuce, swiss chard, spinach, pea shoots, watercress,
      garden cress, mizuna, red mustard, wild rocket and spearmint samples and a total
      of 203 phenolic compounds were tentatively identified and quantified. The main
      naturally phenolic compounds identified correspond to glycosylated flavonoids,
      with exception of green lettuce and spearmint leaves which had a higher content
      of hydroxycinnamic acids. Quantification of the main compounds showed a 10-fold
      higher content of total phenolic content of ruby red lettuce (483mgg(-1)) in
      relation to the other samples, being the lowest values found in the garden cress
      (12.8mgg(-1)) and wild rocket leaves (8.1mgg(-1)). The total phenolic content
      only showed a significant change (p<0.05) after storage in the green lettuce
      (+17.5%), mizuna (+7.8%), red mustard (-23.7%) and spearmint (-13.8%) leaves.
      Within the different classes of phenolic compounds monitored, the flavonols
      showed more stable contents than the hydroxycinnamic and hydroxybenzoic acids,
      although the behavior of each compound varied strongly among samples. 

PMID- 24438835
TI  - Application of ultra-high pressure liquid chromatography linear ion-trap orbitrap
      to qualitative and quantitative assessment of pesticide residues.
AB  - The analysis of pesticides residues using a last generation high resolution and
      high mass accuracy hybrid linear ion trap-Orbitrap mass spectrometer (LTQ
      Orbitrap-MS) was explored. Pesticides were extracted from fruits, fish, bees and
      sediments by QuEChERS and from water by solid-phase with Oasis HLB cartridges.
      Ultra-high pressure liquid chromatography (UHPLC)-LTQ-Orbitrap mass spectrometer
      acquired full scan MS data for quantification, and data dependent (dd) MS(2) and
      MS(3) product ion spectra for identification and/or confirmation. The regression
      coefficients (r(2)) for the calibration curves (two order of magnitude up to the
      lowest calibration level) in the study were >=0.99. The LODs for 54 validated
      compounds were <=2ngmL(-1) (analytical standards). The relative standard
      deviation (RSD), which was used to estimate precision, was always lower than 22%.
      The recovery of extraction and matrix effects ranged from 58 to 120% and from -92
      to 52%, respectively. Mass accuracy was always <=4ppm, corresponding to a maximum
      mass error of 1.6millimass units (mmu). This procedure was then successfully
      applied to pesticide residues in a set of the above-mentioned food and
      environmental samples. In addition to target analytes, this method enables the
      simultaneous detection/identification of non-target pesticides, pharmaceuticals,
      drugs of abuse, mycotoxins, and their metabolites. 

PMID- 24438840
TI  - Chronic fluoxetine exposure alters movement and burrowing in adult freshwater
      mussels.
AB  - The antidepressant fluoxetine is commonly found in aquatic fauna living near or
      downstream from point-sources of municipal waste effluent. Continuous release of
      fluoxetine results in increased effective exposure duration in surface waters,
      resulting in a chronic exposure for animals downstream, particularly in effluent
      dominated ecosystems. Fluoxetine is known to cause disruptions in reproductive
      behavior of freshwater mussels (order Unionoida), including stimulating release
      of gametes, parturition of glochidia (larvae), and changes in lure display and
      foot protrusion. However, the ecological relevance of these effects at
      environmental concentrations is unknown. We conducted a 67-d exposure of adult
      Lampsilis fasciola to fluoxetine concentrations of 0, 0.5, 2.5, and 22.3MUg/L and
      assessed impacts on behavior (lateral movement, burrowing, and filtering) and
      metabolism (glycogen storage and respiration). Mussels treated with 2.5 and
      22.3MUg/L fluoxetine displayed mantle lures significantly (p<0.05) more than
      controls. Animals treated with 22.3MUg/L fluoxetine were statistically more
      likely to have shorter time-to-movement, greater total movement, and initiate
      burrowing sooner than control animals. These observations suggest that increased
      activity of mussels exposed to fluoxetine may result in increased susceptibility
      to predators and may lead to a reduction in energy stores. 

PMID- 24438841
TI  - Looking for the uninsured in Massachusetts? Check opioid dependent persons
      seeking detoxification.
AB  - BACKGROUND: We examined the rate of uninsurance among persons seeking
      detoxification at a large drug treatment program in Massachusetts in 2013, five
      years after insurance mandates. METHODS: We interviewed three hundred and forty
      opioid dependent persons admitted for inpatient detoxification in Fall River,
      Massachusetts. Potential predictors of self-reported insurance status included
      age, gender, ethnicity, employment, homelessness, years of education, current
      legal status, and self-perceived health status. RESULTS: Participants mean age
      was 32 years, 71% were male, and 87% were non-Hispanic Caucasian. Twenty-three
      percent were uninsured. In the multivariate model, the odds of being uninsured
      was positively associated with years of education (OR=1.22, 95% CI=1.03; 1.46,
      p<.05), higher among males than females (OR=2.63, 95% CI=1.33; 5.20, p<.01), and
      inversely associated with age (OR=0.94, 95% CI=0.90; 0.98, p<.01). CONCLUSION:
      Opioid dependent persons recruited from a detoxification program in Massachusetts
      are uninsured at rates far above the state average. With the arrival of the
      Affordable Care Act, drug treatment programs in Massachusetts and nationally will
      be important sites to target to expand health coverage.

PMID- 24438842
TI  - Adolescent alcohol use and alcohol use disorders in Mexico City.
AB  - OBJECTIVE: To estimate the prevalence, sex, age distribution, and socio
      demographic correlates of any alcohol use, consumption patterns, and any alcohol
      use disorder in a representative sample of Mexican adolescents. METHODS: 3005
      youth (52.1% female) aged 12-17 from a stratified multistage area probability
      sample were representative of adolescents residing in the Mexico City
      Metropolitan Area. Alcohol use and disorder and their socio-demographic
      correlates were evaluated with the World Mental Health adolescent version of the
      Composite International Diagnostic Interview. Data were post-stratified to the
      total Mexico City adolescent population. RESULTS: 59% has used alcohol, this
      proportion increasing significantly with age. By age 17, 82.5% has used alcohol.
      Consumption patterns are mostly of low/moderate quantity or infrequent high
      quantity. Lifetime DSM-IV alcohol use disorder criteria are met by 3.8%, reaching
      8.1% for 16-17 years-olds. While males have greater frequency and quantity of
      drinking, there are no gender differences for alcohol use disorders. Non-school
      attending youth have twice the odds of a lifetime (OR=2.0, 95% CI=1.13-3.53) and
      12-month disorder (OR=2.1, 95% CI=1.10-4.15). Low parental monitoring is
      associated with 1.72 times the odds of a lifetime disorder (95% CI=1.10-2.68).
      CONCLUSIONS: Over a third of 12 year-olds had ever drunk an alcoholic beverage in
      their lifetime suggesting that the prevention of alcohol use and disorders must
      begin in late childhood. Initiatives to foment parental monitoring and to
      prevent, identify, and treat alcohol use problems in non-school attending youth
      in particular should be a priority for the wellbeing of Mexico City adolescents.

PMID- 24438843
TI  - Recent cannabis use among adolescent and young adult immigrants in the
      Netherlands--the roles of acculturation strategy and linguistic acculturation.
AB  - BACKGROUND: The present study examined the relation between two different
      acculturation measures (i.e., linguistic acculturation and the acculturation
      strategies integration, separation and marginalization) and past year cannabis
      use. Additionally, we studied the mediating role of affiliation with cannabis
      using peers. METHOD: Data were utilized from i4culture, a Dutch study on
      immigrant adolescents and young adults aged 15-24 years. Participants belonged to
      the five largest immigrant populations in the Netherlands, living in or around
      the four major Dutch cities: Amsterdam, the Hague, Rotterdam, and Utrecht. In
      total, 771 adolescents and young adults (mean age 19.29, SD=2.61, 53.8% female)
      from Surinamese (n=210, 27.2%), Moroccan (n=209, 27.1%), Turkish (n=110, 14.3%),
      Antillean (n=109, 14.1%), and Asian (n=133, 17.3%) backgrounds participated. With
      questionnaires, past year cannabis use, acculturation strategy, linguistic
      acculturation, and affiliation with cannabis-using peers were assessed. RESULTS:
      Using logistic regression analyses, we found no relation between acculturation
      strategy and past year cannabis use (OR=1.25, p=0.38 for separation vs
      integration and OR=0.86, p=0.50 for marginalization vs integration). Linguistic
      acculturation was positively related to cannabis use (OR=2.20, p<0.01).
      Affiliation with cannabis-using peers partly mediated this relation (OR=1.09,
      p<0.01). CONCLUSIONS: Non-Western immigrant youngsters who speak the host
      culture's language at home are more likely to use cannabis than youngsters who
      speak their native language at home. The former group is more likely to affiliate
      with cannabis-using peers, which partly explains their increased risk of cannabis
      use.

PMID- 24438847
TI  - Year in review 2012: Critical Care--respiratory infections.
AB  - Over the last two decades, considerable progress has been made in the
      understanding of disease mechanisms and infection control strategies related to
      infections, particularly pneumonia, in critically ill patients. Patient-centered
      and preventative strategies assume paramount importance in this era of limited
      health-care resources, in which effective targeted therapy is required to achieve
      the best outcomes. Risk stratification using severity scores and inflammatory
      biomarkers is a promising strategy for identifying sick patients early during
      their hospital stay. The emergence of multidrug-resistant pathogens is becoming a
      major hurdle in intensive care units. Cooperation, education, and interaction
      between multiple disciplines in the intensive care unit are required to limit the
      spread of resistant pathogens and to improve care. In this review, we summarize
      findings from major publications over the last year in the field of respiratory
      infections in critically ill patients, putting an emphasis on a newer
      understanding of pathogenesis, use of biomarkers, and antibiotic stewardship and
      examining new treatment options and preventive strategies. 

PMID- 24438850
TI  - Pilot study results for a novel behavior plus nutrition intervention for
      caregivers of young children with type 1 diabetes.
AB  - OBJECTIVE: To present results for a parent-based educational intervention
      targeting mealtime behaviors plus nutrition among families of young children
      (mean age, 5.0 +/- 1.2 years) with type 1 diabetes mellitus (T1DM). METHODS: The
      researchers recruited 9 caregivers who participated in the 6-session intervention
      and completed baseline and posttreatment assessments, which included dietary
      intake, acceptability of diet changes, mealtime behavior, and mean blood glucose
      values. RESULTS: Children's mean daily blood glucose levels decreased from 185 +/
      46 mg/dL to 159 +/- 40 mg/dL (P < .001). There were also decreases in
      problematic parent and child mealtime behaviors. There was no change in
      children's dietary intake indicators that could be detected. CONCLUSIONS AND
      IMPLICATIONS: It appears promising that this targeted behavior plus nutrition
      intervention can improve glycemic control and behavior for young children with
      type 1 diabetes mellitus. Larger, randomized controlled trials will clarify
      significant results, limitations, and sustainability. Techniques within the
      program may have application to current practice.

PMID- 24438851
TI  - Social and emotional adjustment following early pregnancy in young Australian
      women: a comparison of those who terminate, miscarry, or complete pregnancy.
AB  - PURPOSE: To compare social and emotional adjustment including educational
      attainment and substance use in women who had a child, pregnancy termination, or
      miscarriage by young adulthood. METHODS: Data were from a population-based
      longitudinal study of the health and well-being of 1,943 young Australians
      (Victorian Adolescent Health Cohort Study) followed from 15 to 24 years of age.
      The sample was restricted to female participants and based on pregnancies
      reported by age 24 years. Analyses were adjusted for early teenage depressive
      symptoms, cigarette smoking, alcohol use, cannabis use, and parent socioeconomic
      context. RESULTS: A total of 208 pregnancies (in 170 women) were reported from a
      sample of 824 young women by 24 years of age. Compared with those who had never
      been pregnant, those who had a child had lower tertiary education completion and
      a higher risk of nicotine dependence; those who terminated a pregnancy were more
      commonly single and had a higher risk of smoking and alcohol use as well as
      nicotine and alcohol dependence; and those who had a miscarriage had a higher
      risk of depressive symptomatology and binge drinking as well as nicotine and
      cannabis dependence. CONCLUSIONS: Young women who have been pregnant by their mid
      twenties report a range of difficulties in social and emotional adjustment that
      vary across the different pregnancy outcomes. Broad-based psychosocial health
      care is essential not only for young women whose pregnancies proceed to live
      birth, but also for those whose pregnancies end with miscarriage or induced
      abortion.

PMID- 24438852
TI  - The health and well-being of transgender high school students: results from the
      New Zealand adolescent health survey (Youth'12).
AB  - PURPOSE: To report the prevalence of students according to four gender groups
      (i.e., those who reported being non-transgender, transgender, or not sure about
      their gender, and those who did not understand the transgender question), and to
      describe their health and well-being. METHODS: Logistic regressions were used to
      examine the associations between gender groups and selected outcomes in a
      nationally representative high school health and well-being survey, undertaken in
      2012. RESULTS: Of the students (n = 8,166), 94.7% reported being non-transgender,
      1.2% reported being transgender, 2.5% reported being not sure about their gender,
      and 1.7% did not understand the question. Students who reported being transgender
      or not sure about their gender or did not understand the question had compromised
      health and well-being relative to their non-transgender peers; in particular, for
      transgender students perceiving that a parent cared about them (odds ratio [OR],
      .3; 95% confidence interval [CI], .2-.4), depressive symptoms (OR, 5.7; 95% CI,
      3.6-9.2), suicide attempts (OR, 5.0; 95% CI, 2.9-8.8), and school bullying (OR,
      4.5; 95% CI, 2.4-8.2). CONCLUSIONS: This is the first nationally representative
      survey to report the health and well-being of students who report being
      transgender. We found that transgender students and those reporting not being
      sure are a numerically small but important group. Transgender students are
      diverse and are represented across demographic variables, including their sexual
      attractions. Transgender youth face considerable health and well-being
      disparities. It is important to address the challenging environments these
      students face and to increase access to responsive services for transgender
      youth.

PMID- 24438854
TI  - Grand convergence: a future sustainable development goal?

PMID- 24438853
TI  - A cluster analysis-derived classification of psychological distress and illness
      behavior in the medically ill.
AB  - BACKGROUND: The classification of psychological distress and illness behavior in
      the setting of medical disease is still controversial. Current psychiatric
      nosology does not seem to cover the spectrum of disturbances. The aim of this
      investigation was to assess whether the joint use of DSM-IV categories and the
      Diagnostic Criteria for Psychosomatic Research (DCPR), that provide
      identification of syndromes related to somatization, abnormal illness behavior,
      irritable mood, type A behavior, demoralization and alexithymia, could yield
      subtyping of psychosocial variables in the medically ill. METHOD: A cross
      sectional assessment using both DSM-IV and the DCPR was conducted in eight
      medical centers in the Italian Health System. Data were submitted to cluster
      analysis. Participants were consecutive medical out-patients and in-patients for
      whom a psychiatric consultation was requested. A total of 1700 subjects met
      eligibility criteria and 1560 agreed to participate. RESULTS: Three clusters were
      identified: non-specific psychological distress, irritability and affective
      disturbances with somatization. CONCLUSIONS: Two-step cluster analysis revealed
      clusters that were found to occur across clinical settings. The findings indicate
      the need of expanding clinical assessment in the medically ill to include the
      various manifestations of somatization, illness behavior and subclinical distress
      encompassed by the DCPR.

PMID- 24438856
TI  - Effect of treadmill training on endothelial function and walking abilities in
      patients with peripheral arterial disease.
AB  - BACKGROUND: In this prospective study we evaluated the effects of treadmill
      training on patients' walking ability, as well as endothelial function, high
      sensitivity C-reactive protein (hs-CRP), and fibrinogen concentration. METHODS: A
      total of 67 patients with stable intermittent claudication were included in a 12
      week supervised training program. An observational follow-up period then lasted a
      mean of 37 weeks. Forty patients completed follow-up. Changes in blood pressure,
      flow-mediated dilatation (FMD), and treadmill walking performance expressed as
      maximal walking time (MWT) were assessed before and after the training program
      and during the follow-up period. Moreover, ankle/brachial index (ABI), plasma
      levels of hs-CRP, fibrinogen, as well as a lipid profile were assessed before and
      after the training program. RESULTS: Maximal walking time improved significantly
      after treadmill training by 90% (p<0.001) and after follow-up by 64% (p<0.001) in
      comparison to baseline. FMD values increased by 43% (p<0.001) after the training
      program, and by 29% (p=0.058) after follow-up, compared to baseline. We noticed a
      significant decrease in hs-CRP concentration (p=0.025) and an increase in ABI
      values (p=0.039) in response to the treadmill training program. No effect on
      lipid profile was observed. CONCLUSIONS: The 12-week treadmill training program
      prolonged the asymptomatic walking distance. The improvement in FMD indicates a
      systemic effect of the treadmill program on endothelial function. The supervised
      treadmill training provides an effective and safe treatment option in patients
      with PAD. The effects of unsupervised exercise during follow-up period after
      treadmill programs remain tentative and underestimated.

PMID- 24438855
TI  - Is serotonin transporter genotype associated with epigenetic susceptibility or
      vulnerability? Examination of the impact of socioeconomic status risk on African
      American youth.
AB  - We hypothesized that presence of the short allele in the promoter region of the
      serotonin transporter would moderate the effect of early cumulative socioeconomic
      status (SES) risk on epigenetic change among African American youth. Contrasting
      hypotheses regarding the shape of the interaction effect were generated using
      vulnerability and susceptibility frameworks and applied to data from a sample of
      388 African American youth. Early cumulative SES risk assessed at 11-13 years
      based on parent report interacted with presence of the short allele to predict
      differential methylation assessed at age 19. Across multiple tests, a
      differential susceptibility perspective rather than a diathesis-stress framework
      best fit the data for genes associated with depression, consistently
      demonstrating greater epigenetic response to early cumulative SES risk among
      short allele carriers. A pattern consistent with greater impact among short
      allele carriers also was observed using all cytosine nucleotide-phosphate-guanine
      nucleotide sites across the genome that were differentially affected by early
      cumulative SES risk. We conclude that the short allele is associated with
      increased responsiveness to early cumulative SES risk among African American
      youth, leading to epigenetic divergence for depression-related genes in response
      to exposure to heightened SES risk among short allele carriers in a "for better"
      or "for worse" pattern.

PMID- 24438857
TI  - [Pedicular dynamic stabilization system. Functional outcomes and implant-related
      complications for the treatment of degenerative lumbar disc disease with a
      minimum follow-up of 4 years].
AB  - INTRODUCTION: The Dynesys((r)) system is a non-fusion pedicular dynamic
      stabilization system. The aim of our study is to evaluate the clinical outcomes
      in patients with degenerative disc disease and/or stenosis, and to measure the
      prevalence of screw loosening and breakage after 4 years of follow up. MATERIAL
      AND METHODS: All patients who underwent surgery with Dynesys((r)) system in 2008
      were reviewed. The surgery was performed in cases of low back pain of more than 6
      months duration and a positive MRI for degenerative disc disease and/or stenosis.
      RESULTS: A total of 22 patients (11 females, 11 males) with a mean age of 44.40
      +/- 11 years were included, 20 patients (91%) underwent Dynesys((r)) without any
      associated decompression maneuver. The evaluation of back and leg pain (0-10mm)
      showed a mean decrease of 2.4 +/- 2.06 mm (P=.0001). The preoperative value of
      the Oswestry disability index was 52.36 +/- 16.56% (severe functional
      limitation). After surgery, this value was 34.27 +/- 17.87% (moderate functional
      limitation) (P=.001) with a decrease of 18.09 +/- 16.03% (P=.001). A total of 4
      (18%) patients showed signs of loosening screws. One patient (4.5%) had a screw
      breakage. CONCLUSIONS: Surgery with Dynesys((r)) shows favorable long term
      clinical results, however the range of improvement in our series is lower than
      those reported in other studies. Comparative studies between Dynesys((r)) and
      decompression need to be performed in order to isolate the benefit of the dynamic
      stabilization system. Implant-related complications are not uncommon.

PMID- 24438858
TI  - [Osteogenesis imperfecta: Treatment and results of a case series].
AB  - OBJECTIVES: To describe our experience in the management of patients with
      osteogenesis imperfect (OI). MATERIAL AND METHODS: We conducted a retrospective
      study of a series of cases affected with OI treated in the Clinica Univesidad de
      Navarra from 1980 to 2007, with a mean follow up of 17.3 years (7-27 years). We
      collected descriptive data of the sample, the fractures and the deformities, and
      the treatments given. The complications presented and the functional outcomes at
      the end of follow-up were also reviewed. RESULTS: The sample included ten
      patients. Approximately two-thirds (65%) of fractures were sustained in the lower
      limbs. One patient received medical treatment only. Three patients had combined
      medical and surgical treatment. Some type of surgical treatment was performed on
      6 patients. The most common surgery was the Sofield-Millar performed on 37
      occasions, with a third of them requiring revision surgery due to migration of
      the nails. There were 17 episodes of re-fracture. Complications such as non
      union, iatrogenic fractures, and infections, were also observed. The functional
      outcome, according to the Hoffer-Bullock scale, at the end of follow-up was grade
      I/II in 7 patients. CONCLUSIONS: Despite the need for multiple interventions and
      complications presented during follow up, the appropriate treatment of patients
      with OI can provide acceptable functional outcomes.

PMID- 24438859
TI  - [Retrograde nailing in a tibial fracture].
AB  - We describe a case of a severely comminuted type iiia open tibial fracture, with
      distal loss of bone stock (7 cm), total involvement of the tibial joint surface,
      and severe instability of the fibular-talar joint. The treatment performed
      consisted of thorough cleansing, placing a retrograde reamed calcaneal-talar
      tibial nail with proximal and distal blockage, as well as a fibular-talar
      Kirschner nail. Primary closure of the skin was achieved. After 3 weeks, an
      autologous iliac crest bone graft was performed to fill the bone defect, and the
      endomedullary nail, which had protruded distally was reimpacted and dynamized
      distally. The bone defect was eventually consolidated after 16 weeks. Currently,
      the patient can walk without pain the tibial-astragal arthrodesis is
      consolidated.

PMID- 24438860
TI  - [Treatment of Behcet's disease].
AB  - Behcet's disease (BD) is a systemic large-vessel vasculitis characterized by a
      wide clinical spectrum including recurrent oral and genital ulcerations, uveitis,
      vascular, neurological, articular, and gastrointestinal manifestations.
      Therapeutic management of BD depends on the clinical presentation and organ
      involved. Although colchicine, non-steroidal anti-inflammatory agents and topical
      treatments with corticosteroids are often sufficient for mucocutaneous and joint
      involvement, a more aggressive approach with immunosuppressive agents is
      warranted for severe manifestations such as posterior uveitis, retinal
      vasculitis, vascular, neurological and gastrointestinal involvement. However,
      some patients still have refractory disease, relapses, sight threatening eye
      disease, or irreversible organ damage. Recent improvements in the understanding
      of the pathogenic mechanisms have led to the identification of potential targets
      and future therapies for BD. In contrast to current non-specific
      immunosuppressive agents, the emergence of immunomodulatory drugs provides the
      possibility of interfering with specific pathogenic pathways. Novel targeted
      immunosuppressive therapies might be used in the future for BD. 

PMID- 24438861
TI  - [Behcet's disease: Update in 2014].

PMID- 24438862
TI  - Racial susceptibility for QT prolongation in acute drug overdoses.
AB  - BACKGROUND AND PURPOSE: QT prolongation independently predicts adverse
      cardiovascular events in suspected poisoning. We aimed to evaluate the
      association between race and drug-induced QT prolongation for patients with acute
      overdose. METHODS: This was a cross-sectional observational study at two urban
      teaching hospitals. Consecutive adult ED patients with acute drug overdose were
      prospectively enrolled over a two year period. The primary outcome, long-QT, was
      defined using standard criteria: QTc>470 ms in females and>460 ms in males. The
      association between race and drug-induced QT prolongation was tested, considering
      several confounding variables. RESULTS: In 472 patients analyzed (46% female,
      mean age 42.3), QT prolongation occurred in 12.7%. Blacks had two-fold increased
      odds of drug-induced QT prolongation (OR 2.01, CI 1.03-3.91) and Hispanics had
      48% decreased odds of drug-induced QT prolongation (OR 0.52, CI 0.29-0.94).
      CONCLUSIONS: We found significant racial susceptibility to drug-induced QT
      prolongation in this large urban study of acute overdoses.

PMID- 24438870
TI  - Comparison of two blanket surveys of arsenic in tubewells conducted 12 years
      apart in a 25 km(2) area of Bangladesh.
AB  - The arsenic (As) content of groundwater pumped from all tubewells within 61
      contiguous villages of Araihazar, Bangladesh, was determined a first time in 2000
      01 with laboratory measurements and a second time in 2012-13 using the ITS
      Arsenic Econo-Quick kit. The two surveys indicate that the total number of
      tubewells within the area almost doubled from 5560 to 10,879 over 12 years. The
      evolution of the distribution of well ages between the two surveys is consistent
      with a simple model that combines an annual increase of 42 wells/year in the rate
      of installations within the 61 villages starting in 1980 and a 7%/year rate of
      abandonment of wells as a function of well age. Colored placards were posted on
      each pumphead in 2012-13 on the basis of the kit results relative to the WHO
      guideline for As and the Bangladesh standard for As in drinking water: blue for
      As<=10 MUg/L, green>10-50 MUg/L, and red: >50 MUg/L. According to quality-control
      samples collected from 502 tubewells for comparing the kit results with
      laboratory measurements, not a single well labeled blue in 2012-13 should have
      been labeled red and vice-versa. Field-kit testing in 2012-13 did not change the
      status of wells relative to the Bangladesh standard of 876 (87%) out of 1007
      wells with a placard based on laboratory measurements in 2000-01 still attached
      to the pumphead. The high proportion of tubewells believed by households to be
      unsafe (66% out of 2041) that were still used for drinking and cooking in 2012-13
      underlines the need for more widespread testing to identify low-As wells as an
      alternative source of drinking water.

PMID- 24438871
TI  - Pharmaceutical-enantiomers resolution using immobilized polysaccharide-based
      chiral stationary phases in supercritical fluid chromatography.
AB  - Since their introduction on the market the applicability of immobilized
      polysaccharide-based chiral stationary phases in high-performance liquid
      chromatography has been thoroughly investigated. These immobilized phases have
      the benefit to be applicable with a wide range of modifiers, potentially
      extending the application range of the polysaccharide-based stationary phases.
      Because an increasing number of stationary phases are being introduced in the
      field of chiral chromatography it is important to evaluate their
      enantioselectivity in different techniques in order to get an idea about their
      applicability. In this study, three immobilized chiral polysaccharide-based
      stationary phases (Chiralpak IA, IB, and IC) are evaluated in supercritical fluid
      chromatography (SFC) with a test set of pharmaceutical racemates. This is done in
      a three-fold manner: their performance is evaluated (1) using traditional
      modifiers, (2) using mixtures of atypical modifiers, and (3) the results were
      compared to those on coated stationary phases with an equivalent chiral selector.
      To get a visual overview of the enantioselective patterns of the different
      chromatographic systems (mobile and stationary phase combinations), a Principal
      Component Analysis is performed, which allows determining the (dis)similarity
      between individual systems. To assess the complementarity cumulative success
      rates are determined. The immobilized chiral stationary phases prove to yield
      high cumulative success rates. 

PMID- 24438872
TI  - Discrimination of block structures in liquid adsorption chromatography of
      polymers. Simulation and experiment.
AB  - Di- and triblocks can be separated from each other under adsorption conditions
      for the outer block and critical or exclusion conditions for the inner block. If
      the center block is uniform, even a separation according to symmetry can be
      achieved. This behavior is studied in much detail by theory and simulations as
      well as in the chromatographic experiments with block copolymers of ethylene
      oxide and E-caprolactone. 

PMID- 24438873
TI  - Does the Spectrum model accurately predict trends in adult mortality? Evaluation
      of model estimates using empirical data from a rural HIV community cohort study
      in North-Western Tanzania.
AB  - INTRODUCTION: Spectrum epidemiological models are used by UNAIDS to provide
      global, regional and national HIV estimates and projections, which are then used
      for evidence-based health planning for HIV services. However, there are no
      validations of the Spectrum model against empirical serological and mortality
      data from populations in sub-Saharan Africa. METHODS: Serologic, demographic and
      verbal autopsy data have been regularly collected among over 30,000 residents in
      north-western Tanzania since 1994. Five-year age-specific mortality rates (ASMRs)
      per 1,000 person years and the probability of dying between 15 and 60 years of
      age (45Q15,) were calculated and compared with the Spectrum model outputs.
      Mortality trends by HIV status are shown for periods before the introduction of
      antiretroviral therapy (1994-1999, 2000-2005) and the first 5 years afterwards
      (2005-2009). RESULTS: Among 30-34 year olds of both sexes, observed ASMRs per
      1,000 person years were 13.33 (95% CI: 10.75-16.52) in the period 1994-1999,
      11.03 (95% CI: 8.84-13.77) in 2000-2004, and 6.22 (95% CI; 4.75-8.15) in 2005
      2009. Among the same age group, the ASMRs estimated by the Spectrum model were
      10.55, 11.13 and 8.15 for the periods 1994-1999, 2000-2004 and 2005-2009,
      respectively. The cohort data, for both sexes combined, showed that the 45Q15
      declined from 39% (95% CI: 27-55%) in 1994 to 22% (95% CI: 17-29%) in 2009,
      whereas the Spectrum model predicted a decline from 43% in 1994 to 37% in 2009.
      CONCLUSION: From 1994 to 2009, the observed decrease in ASMRs was steeper in
      younger age groups than that predicted by the Spectrum model, perhaps because the
      Spectrum model under-estimated the ASMRs in 30-34 year olds in 1994-99. However,
      the Spectrum model predicted greater 45Q15 mortality than observed in the
      cohort,although the reasons for this over-estimate are unclear [corrected].

PMID- 24438874
TI  - Microvascular dysfunction as a link between obesity, insulin resistance and
      hypertension.
AB  - Impaired microvascular dilatation from any cause and impaired insulin-mediated
      capillary recruitment in particular result in suboptimal delivery of glucose and
      insulin to skeletal muscle, and subsequently impairment of glucose disposal
      (insulin resistance). In addition, microvascular dysfunction, through functional
      and/or structural arteriolar and capillary drop-out, and arteriolar constriction,
      increases peripheral resistance and thus blood pressure. Microvascular
      dysfunction may thus constitute a pathway that links insulin resistance and
      hypertension. Overweight and obesity may be an important cause of microvascular
      dysfunction. Mechanisms linking overweight and obesity to microvascular
      dysfunction include changes in the secretion of adipokines leading to increased
      levels of free fatty acids and inflammatory mediators, and decreased levels of
      adiponectin all of which may impair endothelial insulin signaling. Microvascular
      dysfunction may thus constitute a new treatment target in the prevention of type
      2 diabetes mellitus and hypertension. 

PMID- 24438875
TI  - Kidney injury molecule (KIM)-1 is associated with insulin resistance: results
      from two community-based studies of elderly individuals.
AB  - BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely
      associated with glomerular filtration rate and urinary albumin/creatinine ratio,
      even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM
      1) is a novel, highly specific marker of kidney tubular damage. The role of
      insulin resistance in the development of kidney tubular damage is not previously
      reported. Thus, we aimed to investigate the associations between insulin
      sensitivity (assessed by HOMA) and urinary KIM-1. DESIGN, SETTING, PARTICIPANTS
      AND MEASUREMENTS: Two community-based cohorts of elderly individuals were
      investigated: Prospective Investigation of the vasculature in Uppsala seniors
      (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of
      adult men (ULSAM, n=533; mean age 78 years). RESULTS: Lower insulin sensitivity
      was associated with higher urinary KIM-1 in both cohorts after adjustments for
      age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate,
      and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD
      higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04
      0.22, p=0.007). Results were similar in individuals without diabetes, with normal
      kidney function and normo-albuminuria. CONCLUSIONS: Our findings in elderly
      individuals support the notion that the interplay between an impaired glucose
      metabolism and renal tubular damage is evident even prior to the development of
      diabetes and overt kidney disease.

PMID- 24438876
TI  - Double-strand adeno-associated virus-mediated exendin-4 expression in salivary
      glands is efficient in a diabetic rat model.
AB  - AIM: Exendin-4 (Ex-4) is an agonist of the glucagon-like peptide 1 (GLP-1)
      receptor, approved for the treatment of type 2 diabetes (T2DM). Several
      strategies have been tried to develop stable and efficacious Ex-4 expression
      systems. The purpose of the current study was to determine whether double
      stranded adeno-associated virus (dsAAV)-mediated in vivo expression of exendin-4
      in salivary glands (SG), improves pathology in the Sprague-Dawley (SD) rat model
      of diabetes mellitus (DM). METHODS: The effects of Ex-4 expression by recombinant
      dsAAV-NT4-Ex-4 were evaluated in vitro compared with a single-strand (ss) AAV.
      The dsAAV was delivered into SGs and the blood glucose and insulin levels were
      assessed in a rat model of DM. RESULTS: DsAAV-NT4-Ex-4 virus induces significant
      exendin-4 expression in vitro. Furthermore, Ex-4 expressed from dsAAV virus in
      SGs enhances insulins secretion in vivo and significantly controls the onset of
      hyperglycemia in rat model of DM. CONCLUSIONS: Results suggest that sustained
      secretion of Ex-4 following dsAAV-mediated gene therapy is feasible. SGs appear
      to be promising targets with potential clinical applicability for the treatment
      of DM. This represents the example of a successful use of Ex-4 for diabetes
      therapy, providing support for direct AAV-mediated in vivo as an easy, safe and
      efficient therapeutic strategy.

PMID- 24438877
TI  - Prevalence and clinical implications of painful diabetic peripheral neuropathy in
      type 2 diabetes: results from a nationwide hospital-based study of diabetic
      neuropathy in Korea.
AB  - AIMS: To determine the prevalence and risk factors for painful diabetic
      peripheral neuropathy (PDPN) and evaluate sleep impairment and quality of life in
      patients with PDPN. METHODS: Data from the Korean Diabetes Association Neuropathy
      Study Group were used to evaluate 3999 patients with type 2 diabetes. PDPN was
      diagnosed using visual analogue scales (VAS) and medical history. The patients
      were asked to answer the Brief Pain Inventory-Short Form (BPI-SF), Medical
      Outcomes Study Sleep (MOS-Sleep) Scale, EuroQol (EQ-5D), and VAS. RESULTS: Among
      the patients with diabetic peripheral neuropathy (n=1338), 577 (43.1%) were
      diagnosed with PDPN (14.4% of all patients with type 2 diabetes). PDPN was
      independently associated with age, female gender, fasting plasma glucose,
      hypertension, and previous cerebrovascular events. All pain severity and
      interference measures were higher in patients with PDPN than in non-PDPN
      patients, and patients with PDPN reported more impaired sleep and lower EQ-5D and
      VAS scores. CONCLUSIONS: The prevalence of PDPN in Koreans was comparable to that
      in Western populations. PDPN may impair sleep and quality of life compared with
      non-PDPN, and physicians should carefully consider pain symptoms in patients with
      diabetic peripheral neuropathy.

PMID- 24438878
TI  - Lymphopenia and poor performance status as major predictors for infections among
      residents in long-term care facilities (LTCFs): a prospective cohort study.
AB  - The main aim of this study was to investigate the risk factors and consequence of
      LTCFs-acquired infections in Taiwan through a 16-month follow-up. This
      prospective cohort study invited residents of 10 private LTCFs in Taipei for
      study. For each participant, Karnofsky Performance Scale (KPS), use of feeding
      tube and/or urinary catheters, serum levels of albumin, total cholesterol,
      complete blood count, occurrence of LTCF-acquired infections, all-cause mortality
      were recorded. Overall, a total of 198 LTCF residents entered the study for a
      total of 67,395 resident-days, and 156 participants (79.8+/-9.7 years, 51.3%
      males) complete the follow-up with a total of 67,395 resident-days. During the
      study period, 360 LTCF-acquired infections occurred, and the incidence was
      estimated to be 5.34 episodes per 1000 resident-days. Subjects with LTCF-acquired
      infections were more likely to die than those without infections. Besides,
      subjects with lymphopenia and long-term use of feeding tube and/or urinary
      catheters were significant risk factors for LTCF-acquired infections. However,
      poorer functional status and occurrence of lower respiratory tract infections
      were significant predictive factors for all-cause mortality. In conclusion, the
      period prevalence of LTCF-acquired infections was higher in Taiwan than previous
      reports, but the incidence was similar. In addition to traditional risk factors,
      lymphopenia, a surrogate indicator for immunosenescence, was a significant risk
      factor for LTCF-acquired infections. 

PMID- 24438879
TI  - An inter-rater reliability study of the prescribing indicated medications quality
      indicators of the Assessing Care Of Vulnerable Elders (ACOVE) 3 criteria as a
      potentially inappropriate prescribing tool.
AB  - PURPOSE: There are limited tools to assess potential prescribing omissions (PPOs)
      or underprescribing in the elderly. The ACOVE project defines comprehensive
      quality care indicators for older people and some of these indicators focused on
      appropriate use of medicines. The aim of the present study was to assess the
      inter-rater reliability between observers using the ACOVE 3 prescribing indicated
      medications indicators and compare it with the inter-rater reliability obtained
      for the Screening Tool of Older Person's Prescriptions (STOPP)/Screening Tool to
      Alert Doctors to Right Treatment (START) criteria. METHODS: In the context of an
      observational and multicentric study of a cohort of 672 patients 75 years and
      older who were hospitalized in Internal Medicine services of seven Spanish
      hospitals, an inter-rater reliability study using the ACOVE selected indicators
      and the STOPP/START criteria was carried out between April 2011 and March 2012.
      Three patients were randomly selected in each participating hospital, one for
      each four months of study. RESULTS: A total of 21 patients (mean (SD) age of 84.3
      (5.6) years, 57.1% female) were included in the inter-rater reliability study.
      For the STOPP, START and ACOVE criteria, the median kappa coefficient for the
      seven hospital analyses was 0.97, 0.92 and 0.95, respectively. Out of 123 total
      indicators in only 7 (5.7%) was the kappa coefficient value below 0.75. Only for
      2 (5.6%) of the 37 studies selected ACOVE quality indicators was the kappa
      coefficient value less than 0.75. CONCLUSIONS: A high inter-rater reliability was
      obtained for the selected underprescribing quality indicators of ACOVE 3. These
      quality indicators may be considered a useful tool in detecting underprescribing
      to the elderly patients.

PMID- 24438886
TI  - High-normal serum uric acid predicts the development of chronic kidney disease in
      patients with type 2 diabetes mellitus and preserved kidney function.
AB  - AIMS: We evaluated whether high-normal serum uric acid (SUA) levels can predict
      the development of chronic kidney disease (CKD) in patients with type 2 diabetes
      mellitus and preserved kidney function at baseline. METHODS: This was a
      retrospective observational longitudinal study of patients presenting at the
      Department of Endocrinology and Metabolism, Pusan National University Hospital. A
      total of 512 patients with type 2 diabetes mellitus and preserved kidney function
      (estimated glomerular filtration rate [eGFR] >= 60 mL/min/1.73 m(2)) and
      normouricemia were included. The main outcome was development of CKD of stage 3
      or greater. The patients were divided into four groups according to quartiles of
      SUA levels. RESULTS: During the follow-up period, 62 (12.1%) patients had
      progressed to CKD 3 or greater. The group with the highest-normal range of SUA
      (Q4) showed a higher cumulative incidence of CKD stage 3 or greater than that of
      the other lower quartiles (Q4 vs. Q3; P = 0.037, Q4 vs. Q2; P<0.001, Q4 vs. Q1;
      P<0.001). In a univariate analysis, Q4 was significantly associated with the
      development of CKD 3 or greater (log-rank statistic, 31.93; P<0.001). In a
      multivariate analysis, Q4 (hazard ratio, 2.97; 95% confidence interval, 1.15
      7.71; P = 0.025) showed a significant association with CKD 3 or greater.
      CONCLUSIONS: High-normal SUA may predict the occurrence of CKD stage 3 or greater
      in patients with type 2 diabetes mellitus and preserved kidney function.

PMID- 24438895
TI  - Clinical trials in cytotherapy.

PMID- 24438894
TI  - Putting theory to the test: examining family context, caregiver motivation, and
      conflict in the Family Check-Up model.
AB  - This study examined contextual factors (caregiver depression, family resources,
      ethnicity, and initial levels of youth problem behavior) related to the
      effectiveness of the Family Check-Up (FCU) and evaluated family processes as a
      mediator of FCU intervention response and adolescent antisocial behavior. We
      followed a sample of 180 ethnically diverse youths of families who engaged in the
      FCU intervention. Family data were collected as part of the FCU assessment, and
      youth data were collected over 4 years, from sixth through ninth grade. Findings
      indicated that caregiver depression and minority status predicted greater
      caregiver motivation to change. In turn, caregiver motivation was the only direct
      predictor of FCU intervention response during a 1-year period. Growth in family
      conflict from sixth through eighth grade mediated the link between FCU response
      and ninth-grade antisocial behavior. This study explicitly tested core aspects of
      the FCU intervention model and demonstrated that caregiver motivation is a
      central factor that underlies family response to the FCU. The study also provided
      support for continued examination of family process mechanisms that account for
      enduring effects of the FCU and other family-centered interventions.

PMID- 24438896
TI  - The time is now: moving toward virus-specific T cells after allogeneic
      hematopoietic stem cell transplantation as the standard of care.
AB  - Adoptive immunotherapy-in particular, T-cell therapy-has recently emerged as a
      useful strategy with the potential to overcome many of the limitations of
      antiviral drugs for the treatment of viral complications after hematopietic stem
      cell transplantation. In this review, we briefly summarize the current methods
      for virus-specific T-cell isolation or selection and we report results from
      clinical trials that have used these techniques, focusing specifically on the
      strategies aimed to broaden the application of this technology. 

PMID- 24438897
TI  - Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells
      promote the vascularization of tissue-engineered dermis: an experimental study.
AB  - BACKGROUND AIMS: Tissue-engineered dermis (TED) is thought to be the best
      treatment for skin defect wounds; however, lack of vascular structures in these
      products can cause slow vascularization or even transplant failure. We assessed
      the therapeutic potential of microencapsulated human umbilical cord mesenchymal
      stromal cells (hUCMSCs) expressing vascular endothelial growth factor (VEGF) in
      vascularization of TED. METHODS: hUCMSCs were isolated by means of enzymatic
      digestion and identified by means of testing biological characteristics. hUCMSCs
      were induced to differentiate into dermal fibroblasts in conditioned induction
      media. Collagen-chitosan laser drilling acellular dermal matrix (ADM) composite
      scaffold was prepared by means of the freeze dehydration and dehydrothermal cross
      linking method. hUCMSC-derived fibroblasts were implanted on composite scaffolds
      to construct TED. TED with microencapsulated VEGF gene-modified hUCMSCs was then
      transplanted into skin defect wounds in pigs. The angiogenesis of TED at 1 week
      and status of wound healing at 3 weeks were observed. RESULTS: The collagen
      chitosan laser ADM composite has a uniform microporous structure. This composite
      has been used to grow hUCMSC-derived fibroblasts in vitro and to successfully
      construct stem cell-derived TED. Microencapsulated VEGF gene-modified hUCMSCs
      were prepared with the use of a sodium alginate-barium chloride one-step
      encapsulation technology. Seven days after the transplantation of the stem cell
      derived TED and microencapsulated VEGF gene-modified hUCMSCs into the skin defect
      wounds on the backs of miniature pigs, the VEGF expression increased and the TED
      had a higher degree of vascularization. Re-epithelialization of the wound was
      completed after 3 weeks. CONCLUSIONS: Microencapsulated VEGF gene-modified
      hUCMSCs can effectively improve the vascularization of TED and consequently the
      quality of wound healing.

PMID- 24438898
TI  - Evaluation of human platelet lysate versus fetal bovine serum for culture of
      mesenchymal stromal cells.
AB  - Culture media for therapeutic cell preparations-such as mesenchymal stromal cells
      (MSCs)-usually comprise serum additives. Traditionally, fetal bovine serum is
      supplemented in basic research and in most clinical trials. Within the past
      years, many laboratories adapted their culture conditions to human platelet
      lysate (hPL), which further stimulates proliferation and expansion of MSCs.
      Particularly with regard to clinical application, human alternatives for fetal
      bovine serum are clearly to be preferred. hPL is generated from human platelet
      units by disruption of the platelet membrane, which is commonly performed by
      repeated freeze and thaw cycles. Such culture supplements are notoriously ill
      defined, and many parameters contribute to batch-to-batch variation in hPL such
      as different amounts of plasma, a broad range of growth factors and donor
      specific effects. The plasma components of hPL necessitate addition of
      anticoagulants such as heparins to prevent gelatinization of hPL medium, and
      their concentration must be standardized. Labels for description of hPL-such as
      "xenogen-free," "animal-free" and "serum free"-are not used consistently in the
      literature and may be misleading if not critically assessed. Further analysis of
      the precise composition of relevant growth factors, attachment factors, microRNAs
      and exosomes will pave the way for optimized and defined culture conditions. The
      use of hPL has several advantages and disadvantages: they must be taken into
      account because the choice of cell culture additive has major impact on cell
      preparations. 

PMID- 24438899
TI  - Human mesenchymal stromal cells can uptake and release ciprofloxacin, acquiring
      in vitro anti-bacterial activity.
AB  - BACKGROUND AIMS: Traditional antibiotic therapy is based on the oral or systemic
      injection of antibiotics that are often unable to stop a deep infection (eg,
      osteomyelitis). We studied whether or not bone marrow stromal cells (BM-MSCs) are
      able to uptake and release ciprofloxacin (CPX), a fluoroquinolone considered the
      drug of choice for the treatment of chronic osteomyelitis because of its
      favorable penetration into poorly vascularized sites of infection. METHODS: Human
      bone marrow stromal cells (BM-MSCs) were primed with CPX (BM-MSCsCPX) according
      to a methodology previously standardized in our laboratory for paclitaxel (PTX).
      The anti-microbial activity of CPX released from BM-MSCs cells (BM-MSCsCPX-CM) or
      supernatant from cell lysate (BM-MSCsCPX-LYS) was evaluated by agar dilution and
      microdilution methods on three bacterial strains (Staphylococcus aureus,
      Escherichia coli and Pseudomonas aeruginosa). To investigate whether or not
      primed cells (BM-MSCsCPX) were able to directly act on the bacterial growth, co
      colture was performed by mixing E. coli suspension to an increasing number of BM
      MSCsCPX. The anti-bacterial activity was determined as number of BM-MSCsCPX that
      completely inhibited bacterial growth. RESULTS: The results demonstrated that BM
      MSCsCPX are able to uptake and then release CPX in the conditioned medium. The
      loaded antibiotic maintains its active form throughout the process as tested on
      bacteria. CONCLUSIONS: Our findings suggest that CPX-loaded MSCs may represent an
      important device for carrying and delivering CPX (and perhaps other antibiotics)
      into infected deep microenvironments; they could be used for local application
      and by systemic infusion when their homing capacity into the bone is cleared.

PMID- 24438900
TI  - Human mesenchymal stromal cells transiently increase cytokine production by
      activated T cells before suppressing T-cell proliferation: effect of interferon
      gamma and tumor necrosis factor-alpha stimulation.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) suppress T-cell proliferation,
      especially after activation with inflammatory cytokines. We compared the dynamic
      action of unprimed and interferon (IFN)-gamma plus tumor necrosis factor (TNF)
      alpha-pretreated human bone marrow-derived MSCs on resting or activated T cells.
      METHODS: MSCs were co-cultured with allogeneic peripheral blood mononuclear cells
      (PBMCs) at high MSC-to-PBMC ratios in the absence or presence of concomitant
      CD3/CD28-induced T-cell activation. The kinetic effects of MSCs on cytokine
      production and T-cell proliferation, cell cycle and apoptosis were assessed.
      RESULTS: Unprimed MSCs increased the early production of IFN-gamma and
      interleukin (IL)-2 by CD3/CD28-activated PBMCs before suppressing T-cell
      proliferation. In non-activated PBMC co-cultures, low levels of IL-2 and IL-10
      synthesis were observed with MSCs in addition to low levels of CD69 expression by
      T cells and no T-cell proliferation. MSCs also decreased apoptosis in resting and
      activated T cells and inhibited the transition of these cells into the sub-G0/G1
      and the S phases. With inhibition of indoleamine 2,3 dioxygenase, MSCs increased
      CD3/CD28-induced T-cell proliferation. After priming with IFN-gamma plus TNF
      alpha, MSCs were less potent at increasing cytokine production by CD3/CD28
      activated PBMCs and more effective at inhibiting T-cell proliferation but had
      preserved anti-apoptotic functions. CONCLUSIONS: Unprimed MSCs induce a transient
      increase in IFN-gamma and IL-2 synthesis by activated T cells. Pre-treatment of
      MSCs with IFN-gamma plus TNF-alpha may increase their effectiveness and safety in
      vivo.

PMID- 24438901
TI  - Evaluation of gametogenic potential of vitrified human umbilical cord Wharton's
      jelly-derived mesenchymal cells.
AB  - BACKGROUND AIMS: Vitrification as an advanced cryopreservation method is
      recommended for cell storage toward future applications. The purpose of this
      report was to appraise whether gametogenic potential of these cells is altered by
      vitrification. METHODS: A two steps method was applied for hUCM cells
      vitrification. An n-hUCM group of hUCM cells served as control. In order to
      differentiation of hUCM cells into male germ cells, the cells were induced by
      retinoic acid, testosterone and testicular-cell-conditioned medium. To evaluate
      induced hUCM cells toward germ cells, we used immunocytochemistry and karyotyping
      methods. RESULTS: v-hUCM cells similar to n-hUCM cells formed flat cells after
      gametogenic induction, and showed protein expression of germ-cell-specific
      markers DAZL, VASA (DDX4) and SCP3. Karyotyping pattern remained unchanged in the
      either groups. CONCLUSIONS: The analysis of these results demonstrates that
      vitrification does not alter differentiation potential of hUCMs to male germ like
      cells. These results may set an in vitro pattern to study germ-cell formation
      from hUCM cells and also as a potential source of sperms for male infertility.

PMID- 24438902
TI  - Open-label, multi-center, non-randomized, single-arm study to evaluate the safety
      and efficacy of dendritic cell immunotherapy in patients with refractory solid
      malignancies, on supportive care.
AB  - BACKGROUND AIMS: A phase II clinical trial of an autologous dendritic cell (DC)
      formulation for the management of refractory solid malignant tumors was conducted
      across six sites in India with an objective to study safety and efficacy.
      METHODS: A total of 51 patients with refractory cancer (either sex) with life
      expectancy >=3 months, Eastern Cooperative Oncology Group score <=2, available
      tumor tissue and adequate organ and bone marrow function were recruited.
      Monocytes obtained by leukapheresis, differentiated into DCs by cytokines and
      primed with autologous tumor lysate (fresh tissue biopsy or paraffin block). On
      the 8th day, mature DCs were analyzed for expression of CD40, CD80, CD83, CD86,
      DC205 and DC209. The treatment regime consisted of six doses (intravenous) over
      14 weeks with 2 post-treatment follow-up visits, 6 weeks apart. Safety was
      assessed at all visits and responses were evaluated on days 58, 100 and 184 or at
      end of the study. RESULTS: A total of 38 patients were evaluated for safety and
      efficacy. One adverse event classified as possibly related was an episode of
      rigors or chills with mild pyrexia during one infusion. Objective response rate
      by Response Evaluation Criteria In Solid Tumors was 28.9% (11/38) and immune
      related response criteria was 42.1% (16/38); 90% confidence interval for
      objective response rate was (17.2, 43.3) and (28.5, 56.7) by Response Evaluation
      Criteria In Solid Tumors and immune-related response criteria, respectively. The
      median time to treatment progression was >9 weeks. Median overall survival was
      397 days. An increase in the expression of interferon-gamma was not significant.
      CONCLUSIONS: Therapy was safe. The responses, time to treatment progression and
      survival are encouraging for patients with aggressive refractory disease.

PMID- 24438903
TI  - Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells
      to treat patients with non-revascularizable critical limb ischemia.
AB  - BACKGROUND AIMS: Non-revascularizable critical limb ischemia (CLI) is the most
      severe stage of peripheral arterial disease, with no therapeutic option.
      Extensive preclinical studies have demonstrated that adipose-derived stroma cell
      (ASC) transplantation strongly improves revascularization and tissue perfusion in
      ischemic limbs. This study, named ACellDREAM, is the first phase I trial to
      evaluate the feasibility and safety of intramuscular injections of autologous ASC
      in non-revascularizable CLI patients. METHODS: Seven patients were consecutively
      enrolled, on the basis of the following criteria: (i) lower-limb rest pain or
      ulcer; (ii) ankle systolic oxygen pressure <50 or 70 mm Hg for non-diabetic and
      diabetic patients, respectively, or first-toe systolic oxygen pressure <30 mm Hg
      or 50 mm Hg for non-diabetic and diabetic patients, respectively; (iii) not
      suitable for revascularization. ASCs from abdominal fat were grown for 2 weeks
      and were then characterized. RESULTS: More than 200 million cells were obtained,
      with almost total homogeneity and no karyotype abnormality. The expressions of
      stemness markers Oct4 and Nanog were very low, whereas expression of telomerase
      was undetectable in human ASCs compared with human embryonic stem cells. ASCs
      (10(8)) were then intramuscularly injected into the ischemic leg of patients,
      with no complication, as judged by an independent committee. Trans-cutaneous
      oxygen pressure tended to increase in most patients. Ulcer evolution and wound
      healing showed improvement. CONCLUSIONS: These data demonstrate the feasibility
      and safety of autologous ASC transplantation in patients with objectively proven
      CLI not suitable for revascularization. The improved wound healing also supports
      a putative functional efficiency.

PMID- 24438904
TI  - Cell viability and proliferation capability of long-term human dental pulp stem
      cell cultures.
AB  - BACKGROUND AIMS: Evaluation of cell viability is one of the most important steps
      of the quality control process for therapeutic use of cells. The aim of this
      study was to evaluate the long-term cell viability profile of human dental pulp
      stem cell (hDPSC) subcultures (beyond 10 passages) to determine which of these
      passages are suitable for clinical use and to identify the cell death processes
      that may occur in the last passages. METHODS: Four different cell viability
      assays were combined to determine the average cell viability levels at each cell
      passage: trypan blue exclusion test, water-soluble tetrazolium 1 (WST-1),
      LIVE/DEAD Viability/Cytotoxicity Kit and electron probe x-ray microanalysis
      (EPXMA). Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) assay and caspase 4 and BCL7C Western blotting, and
      cell proliferation was analyzed by WST-1 and proliferating cell nuclear antigen
      protein detection. RESULTS: hDPSCs showed high average cell viability levels from
      passages 11-14, with adequate cytoplasmic and mitochondrial functionality at
      these subcultures. A non-significant trend to decreased cell proliferation was
      found from passages 16-20. EPXMA and TUNEL analyses suggested that a pre
      apoptotic process could be activated from passages 15-20 (P < 0.001), with a
      correlation with caspase 4 and BCL7C expression. CONCLUSIONS: hDPSCs
      corresponding to passages 11-14 show adequate cell function, proliferation and
      viability. These cells could be considered as potentially useful for clinical
      applications.

PMID- 24438905
TI  - Treatment of multiple solitary plasmacytomas with cytokine-induced killer cells.
AB  - BACKGROUND AIMS: Currently available treatment methods for advanced plasmacytoma
      include surgery, chemotherapy, radiotherapy, immunomodulatory agents,
      hematopoietic stem cell transplantation and donor lymphocyte infusion. We report
      a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old
      Asian man with multiple bone lesions, in whom autologous cytokine-induced killer
      (CIK) cells were administered in an effort to eliminate residual tumor lesions.
      METHODS: CIK cells were infused monthly for 21 courses. RESULTS: The patient has
      survived 63 months since the first hospital visit without disease progression for
      40 months. CONCLUSIONS: This case represents the first report of autologous CIK
      cell immunotherapy used successfully to suppress multiple solitary plasmacytomas
      and resolve bone lesions.

PMID- 24438906
TI  - Letter to the editor.

PMID- 24438907
TI  - The role of SDF-1alpha-ECM crosstalk in determining neural stem cell fate.
AB  - The consequences of central nervous system injury are far-reaching and
      debilitating and, while an endogenous repair response to neural injury has been
      observed in recent years, the mechanisms behind this response remain unclear.
      Neural progenitor/stem cell (NPSC) migration to the site of injury from the
      neural stem cell niches (e.g. subventricular zone and hippocampus) has been
      observed to be vasophilic in nature. While the chemotactic stimuli directing NPSC
      homing to injury is not well established, it is thought to be due in part to an
      increasing gradient of chemotactic cytokines, such as stromal cell-derived factor
      1alpha (SDF-1alpha). Based on these recent findings, we hypothesize that critical
      crosstalk between SDF-1alpha and the extracellular matrix (ECM) drives injury
      induced NPSC behavior. In this study, we investigated the effect of SDF-1alpha
      and ECM substrates (Matrigel, laminin, and vitronectin) on the migration,
      differentiation, and proliferation of NPSCs in vitro using standard assays. The
      results demonstrated that SDF-1alpha and laminin-based ECM (Matrigel and laminin)
      significantly and synergistically enhanced NPSC migration and acute neuronal
      differentiation. These effects were significantly attenuated with the addition of
      AMD3100 (an antagonist against the SDF-1alpha receptor, CXCR4). SDF-1alpha alone
      significantly increased NPSC proliferation regardless of ECM substrate, however
      no synergy was observed between SDF-1alpha and the ECM. These results serve to
      elucidate the relationship between adhesive and soluble signaling factors of
      interest and their effect on NPSC behavior following neural injury. Furthermore,
      these results better inform the next generation of biomaterials aimed at
      stimulating endogenous neural regeneration for neural injury and
      neurodegenerative diseases. 

PMID- 24438908
TI  - Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2
      N, 6-O-sulfated chitosan nanoparticles.
AB  - Although rhBMP-2 has excellent ability to accelerate the repair of normal bone
      defects, limitations of its application exist in the high cost and potential side
      effects. This study aimed to develop a composite photopolymerisable hydrogel
      incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles (PH/rhBMP
      2/NPs) as the bone substitute to realize segmental bone defect repair at a low
      growth factor dose. Firstly rhBMP-2 loaded 2-N, 6-O-sulfated chitosan
      nanoparticles (rhBMP-2/NPs) were prepared and characterized by DLS and TEM.
      Composite materials, PH/rhBMP-2/NPs were developed and investigated by SEM-EDS as
      well as a series of physical characterizations. Using hMSCs as an in vitro cell
      model, composite photopolymerisable hydrogels incorporating NPs (PH/NPs) showed
      good cell viability, cell adhesion and time dependent cell ingrowth. In vitro
      release kinetics of rhBMP-2 showed a significantly lower initial burst release
      from the composite system compared with the growth factor-loaded particles alone
      or encapsulated directly within the hydrogel, followed by a slow release over
      time. The bioactivity of released rhBMP-2 was validated by alkaline phosphatase
      (ALP) activity as well as a mineralization assay. In in vivo studies, the
      PH/rhBMP-2/NPs induced ectopic bone formation in the mouse thigh. In addition, we
      further investigated the in vivo effects of rhBMP-2-loaded scaffolds in a rabbit
      radius critical defect by three dimensional micro-computed tomographic (MUCT)
      imaging, histological analysis, and biomechanical measurements. Animals implanted
      with the composite hydrogel containing rhBMP-2-loaded nanoparticles underwent
      gradual resorption with more pronounced replacement by new bone and induced
      reunion of the bone marrow cavity at 12 weeks, compared with animals implanted
      with hydrogel encapsulated growth factors alone. These data provided strong
      evidence that the composite PH/rhBMP-2/NPs are a promising substitute for bone
      tissue engineering.

PMID- 24438909
TI  - The induction of bone formation by the recombinant human transforming growth
      factor-beta3.
AB  - Implantation of recombinant human transforming growth factor-beta3 (hTGF-beta3)
      with coral-derived calcium carbonate-based macroporous bioreactors with limited
      conversion to hydroxyapatite (7% HA/CC) in the rectus abdominis muscle of the non
      human primate Chacma baboon Papio ursinus induces endochondral bone formation.
      The exact mechanisms by which hTGF-beta3 signalling induces bone in heterotopic
      sites of P. ursinus are not known. Coral-derived 7% HA/CC bioreactors with and
      without 125 MUg hTGF-beta3 were implanted in triplicate in the rectus abdominis
      muscle of 6 adult baboons. 7% HA/CC bioreactors either with or without hTGF-beta3
      were loaded with 125 MUg of recombinant human Noggin (hNoggin), a bone
      morphogenetic proteins (BMPs) antagonist. Tissues on day 15, 60 and 90 were
      analysed by histomorphometry and quantitative reverse-transcriptase polymerase
      chain reaction (qRT-PCR). Down-regulation of BMP-2 characterized 7% HA/CC
      constructs preloaded with 125 MUg hNoggin with Noggin down-regulated on day 60
      and 90 together with lack of TGF-beta3 expression. Down-regulation of BMP-2
      correlated with minimal bone formation by induction. hTGF-beta3/hNoggin pre
      treated bioreactors up-regulated BMP-2 but only on day 90 together with a
      significant down-regulation of Noggin on day 60 and 90, correlating with the
      induction of bone formation, albeit limited, on day 90 at the periphery of the
      macroporous bioreactors only. hTGF-beta3 treated bioreactors significantly down
      regulated BMP-2 on day 15 whilst up-regulating BMP-2 on day 60 and 90, together
      with down-regulation of Noggin on day 60 and 90 correlating with the prominent
      induction of bone formation. hTGF-beta3 significantly up-regulated RUNX-2 and
      Osteocalcin expression on day 15 controlling the differentiation of progenitor
      stem cells into the osteoblastic lineage. The induction of bone as initiated by
      hTGF-beta3 in the rectus abdominis muscle of P. ursinus is via the BMPs pathway
      with hTGF-beta3 controlling the induction of bone formation by regulating the
      expression of BMPs via Noggin expression. These results unequivocally demonstrate
      that hTGF-beta3 elicits bone induction by up-regulation of endogenous BMP-2 and
      is blocked by hNoggin.

PMID- 24438910
TI  - Increased vocal intensity due to the Lombard effect in speakers with Parkinson's
      disease: simultaneous laryngeal and respiratory strategies.
AB  - PURPOSE: The objective of the present study was to investigate whether speakers
      with hypophonia, secondary to Parkinson's disease (PD), would increases their
      vocal intensity when speaking in a noisy environment (Lombard effect). The other
      objective was to examine the underlying laryngeal and respiratory strategies used
      to increase vocal intensity. METHODS: Thirty-three participants with PD were
      included for study. Each participant was fitted with the SpeechViveTM device that
      played multi-talker babble noise into one ear during speech. Using acoustic,
      aerodynamic and respiratory kinematic techniques, the simultaneous laryngeal and
      respiratory mechanisms used to regulate vocal intensity were examined. RESULTS:
      Significant group results showed that most speakers with PD (26/33) were
      successful at increasing their vocal intensity when speaking in the condition of
      multi-talker babble noise. They were able to support their increased vocal
      intensity and subglottal pressure with combined strategies from both the
      laryngeal and respiratory mechanisms. Individual speaker analysis indicated that
      the particular laryngeal and respiratory interactions differed among speakers.
      CONCLUSIONS: The SpeechViveTM device elicited higher vocal intensities from
      patients with PD. Speakers used different combinations of laryngeal and
      respiratory physiologic mechanisms to increase vocal intensity, thus suggesting
      that disease process does not uniformly affect the speech subsystems. LEARNING
      OUTCOMES: Readers will be able to: (1) identify speech characteristics of people
      with Parkinson's disease (PD), (2) identify typical respiratory strategies for
      increasing sound pressure level (SPL), (3) identify typical laryngeal strategies
      for increasing SPL, (4) define the Lombard effect.

PMID- 24438911
TI  - The efficacy of the cycles approach: a multiple baseline design.
AB  - The purpose of this study was to evaluate the efficacy of the Cycles Phonological
      Remediation Approach as an intervention for children with speech sound disorders
      (SSD). A multiple baseline design across behaviors was used to examine
      intervention effects. Three children (ages 4;3 to 5;3) with moderate-severe to
      severe SSDs participated in two cycles of therapy. Three phonological patterns
      were targeted for each child. Generalization probes were administered during
      baseline, intervention, and follow-up phases to assess generalization and
      maintenance of learned skills. Two of the three participants exhibited
      statistically and clinically significant gains by the end of the intervention
      phase and these effects were maintained at follow-up. The third participant
      exhibited significant gains at follow-up. Phonologically known target patterns
      showed greater generalization than unknown target patterns across all phases.
      Individual differences in performance were examined at the participant level and
      the target pattern level. LEARNING OUTCOMES: The reader will be able to: (1)
      enumerate the three major components of the cycles approach, (2) describe factors
      that should be considered when selecting treatment targets, and (3) identify
      variables that may affect a child's outcome following cycles treatment.

PMID- 24438912
TI  - [Utility of radioguided surgery in splenosis].
AB  - Splenosis is a common finding after traumatic rupture of the spleen or
      therapeutic splenectomy, defined as a heterotopic autotransplantation of the
      spleen in peritoneal cavity and surface. In splenectomized patients due to
      hematologic disease, splenosis can lead to disease recurrence. We present a case
      of splenosis in a patient with idiopathic thrombocytopenic purpura who relapsed
      after splenectomy. For its localization, conventional imaging and scintigraphy
      with (99m)Tc-denatured red cells was performed, and at least five splenic foci
      were observed. Given the difficult intraoperative localization of these nodules,
      radioguided surgery was performed, with excellent localization and removal of all
      known nodules and multiple peritoneal implants of millimeter size that were not
      previously observed. We conclude that radioguided surgery is an excellent tool
      for locating foci of peritoneal splenosis, which have difficult access, thus
      avoiding early recurrence of the disease.

PMID- 24438913
TI  - Extensive extra-osseous accumulation of (99m)Tc-hydroximethylene diphosphonate in
      a patient with unsuspected dermatomyositis: Whole-body scintigraphy and SPECT/CT.

PMID- 24438914
TI  - An incidental finding of a nonpathological lumbar transverse process fracture on
      (18)F-FDG PET-CT in a patient diagnosed of breast cancer.

PMID- 24438915
TI  - Extrahepatic visualization in the distribution of falciform artery in
      posttreatment Bremsstrahlung images after radioembolization with (90)Y
      microspheres.
AB  - We report the case of a 39-year-old female with metastatic colorectal cancer.
      Pretreatment SPECT/CT imaging revealed extrahepatic tracer accumulation along the
      falciform artery distribution. Prior to the administration of (90)Y microspheres,
      hepatic arterial anatomy was evaluated angiographically. It was not possible to
      identify the hepatic falciform artery so that no coil-embolization was performed.
      The patient tolerated the treatment well with only mild pain around the umbilicus
      during the procedure that spontaneously abated. As far as we know, this is the
      first report of Bremsstrahlung SPECT/CT images that has clearly shown that the
      microspheres accumulation in the anterior abdominal wall corresponds to hepatic
      falciform artery distribution on CT.

PMID- 24438916
TI  - Neural correlates of de novo depression following left temporal lobe epilepsy
      surgery: a voxel based morphometry study of pre-surgical structural MRI.
AB  - PURPOSE: To investigate cerebral grey matter (GM) volumetric abnormalities in
      temporal lobe epilepsy (TLE) patients who develop de novo depression following
      TLE surgery using voxel-based morphometry (VBM). METHODS: We retrospectively
      examined pre-surgical grey matter (GM) volumes in 30 patients with TLE due to
      unilateral left-sided hippocampal sclerosis using 1.5-T MRI scan, which were
      segmented with optimised VBM parameters and normalised to a sample template using
      DARTEL, with SPM8 software. Voxel-wise GM differences between patients that
      developed de novo post-surgical depression (n=5) were compared with patients with
      no pre- or postoperative psychiatric diagnoses (n=25), using independent samples
      t-tests with age, gender and secondary generalised tonic-clonic seizures (SGTCS)
      as covariates (p<.001, unc). KEY FINDINGS: Reduced preoperative bilateral GM in
      orbitofrontal cortices (OFC) and ipsilateral cingulate gyrus and thalamus were
      significantly associated with the development of de novo depression within 4
      years postoperatively. Further analyses revealed no differences in seizure
      freedom (ILAE 1 vs 2-6) or postoperative memory decline between the groups.
      SIGNIFICANCE: Although the development of postoperative de novo depression
      following TLE surgery is likely to be multi-factorial, our results suggest that
      bilateral OFC and ipsilateral cingulate gyrus and thalamic atrophy in left-sided
      TLE patients may play a modulatory role. Abnormalities in these areas have also
      been implicated in primary mood disorders. Prospective neuroimaging studies with
      larger cohorts are warranted to replicate these results, and further elucidate
      the neural correlates of de novo depression.

PMID- 24438920
TI  - Angiographic evolution of myocardial perfusion impairment in a single case of
      Tako-Tsubo like syndrome.

PMID- 24438921
TI  - Quick recovery of left ventricular dyssynchrony after anticoagulation in acute
      pulmonary embolism.

PMID- 24438922
TI  - Performance of Framingham cardiovascular disease (CVD) predictions in the
      Rotterdam Study taking into account competing risks and disentangling CVD into
      coronary heart disease (CHD) and stroke.
AB  - BACKGROUND: To evaluate the performance of Framingham predictions of
      cardiovascular disease (CVD) risk corrected for the competing risk of non-CVD
      death, in an independent European cohort of older individuals and subsequently
      extend the predictions by disentangling CVD into coronary heart disease (CHD) and
      stroke separately. METHODS: We used the Rotterdam Study data, a prospective
      cohort study of individuals aged 55 years and older (N=6004), to validate the
      Framingham predictions of CVD, defined as first occurrence of myocardial
      infarction, coronary death or stroke during 15 years of follow-up, corrected for
      the competing risk of non-CVD death. We subsequently estimated the risks of CHD
      and stroke separately, and used the sum as a predictor for the total CVD risk.
      Calibration plots and c-statistics were used to evaluate the performance of the
      models. RESULTS: Performance of the Framingham predictions was good in the low-
      to intermediate risk (<=30%, 15-year CVD risk) (17.5% observed vs. 16.6%
      expected) but poorer in the higher risk (>30%) categories (36.3% observed vs.
      44.1% expected). The c-statistic increased from 0.66 to 0.69 after refitting.
      Separately estimating CHD and stroke revealed considerable heterogeneity with
      regard to the contribution of CHD and stroke to total CVD risk. CONCLUSIONS:
      Framingham CVD risk predictions perform well in the low- to intermediate risk
      categories in the Rotterdam Study. Disentangling CVD into CHD and stroke
      separately provides additional information about the individual contribution of
      CHD and stroke to total individual CVD risk.

PMID- 24438923
TI  - The forgotten valvulopathy and the forgotten ventricle?

PMID- 24438924
TI  - Fixed-dose aspirin-clopidogrel combination enhances compliance to aspirin after
      acute coronary syndrome.

PMID- 24438925
TI  - Al-Akhawayni's account of carotid sinus hypersensitivity.

PMID- 24438926
TI  - Cardiovascular operations in Behcet's disease.

PMID- 24438927
TI  - The role of cold stress in predicting extra cardiovascular and respiratory
      admissions.

PMID- 24438928
TI  - Association of soy food intake with risk and biomarkers of coronary heart disease
      in Chinese men.

PMID- 24438929
TI  - Determinants of quality of life in patients with atrial fibrillation.

PMID- 24438930
TI  - Avicenna's description of cardiac tamponade.

PMID- 24438931
TI  - A hot flush signals the way to a woman's heart.

PMID- 24438932
TI  - Age and gender-specific changes in left ventricular systolic function in human
      volunteers.

PMID- 24438933
TI  - Unusual cause of hypoxemia in myocardial infarction: interventional management.

PMID- 24438934
TI  - Hyperpolarization-activated current-mediated slow afterhyperpolarization in
      myelinated Ah-type of baroreceptor neurons isolated from adult female rats.

PMID- 24438935
TI  - Electrocardiography not always confirm arrhythmogenic right ventricular
      cardiomyopathy - the value of lead aVR.

PMID- 24438936
TI  - Rhazes' description of a case with aortic regurgitation.

PMID- 24438937
TI  - Genetic polymorphisms of human cardiac troponins as an unrecognized challenge for
      diagnosing myocardial injury.

PMID- 24438938
TI  - Augmentation of the J wave by rapid pacing in a patient with vasospastic angina.

PMID- 24438939
TI  - Carotid intima-media thickness is a useful screening tool to detect coronary
      artery plaque in type 2 diabetic patients with zero calcium score.

PMID- 24438940
TI  - Allogeneic mesenchymal progenitor cells for posterolateral lumbar spine fusion in
      sheep.
AB  - BACKGROUND CONTEXT: Osteoconductive porous ceramic bone graft materials
      supplemented with mesenchymal precursor cells (MPC) derived from autologous bone
      marrow aspirates have been shown to stimulate successful interbody and
      posterolateral spine fusion in preclinical models. Recent advances in
      immunomagnetic cell sorting have enabled purification and isolation of
      pluripotent stem cells from marrow aspirates and have expanded stem cell
      technology to allogeneic cell sources. Allogeneic MPC technology combined with
      appropriate synthetic biomaterial carriers could provide both the osteogenic and
      osteoconductive components needed for successful posterolateral spine fusion
      without the need for autologous bone harvest or expensive recombinant protein
      technology. PURPOSE: To determine the safety and efficacy of a
      hydroxyapatite:tricalcium phosphate graft material supplemented with allogeneic
      mesenchymal precursor cells in posterolateral lumbar spine fusion using an ovine
      model. STUDY DESIGN: Skeletally mature ewes underwent single-level instrumented
      posterolateral lumbar spine fusion using either autograft (AG),
      hydroxyapatite:tricalcium phosphate carrier (CP), or CP supplemented with
      allogeneic mesenchymal progenitor cells (MPCs). Three doses of MPCs were
      evaluated: 25 * 106 cells (low dose, LD), 75 * 106 cells (mid dose, MD), and 225
      * 106 cell (high dose, HD). Animals survived for either 4 or 9 months. METHODS:
      Plain radiographs were acquired and scored for bridging bone at regular intervals
      during healing to monitor fusion development. Hematology, coagulation, and serum
      chemistry were monitored at regular intervals throughout the study to monitor
      animal health. After necropsy, computed tomography, high-resolution radiography,
      biomechanical testing, organ pathology, bone histopathology, and bone
      histomorphometry were conducted to monitor the safety and ascertain the efficacy
      of MPC treatment. RESULTS: MPC treatment in this spine fusion model resulted in
      no observed adverse systemic or local tissue responses. Radiographically, fusion
      scores for MPC-treated animals were uniformly higher compared with those treated
      with carrier alone (CP) after 3 months and continued the same trend throughout 9
      month of healing. Quantitative computed tomography confirmed better connectivity
      of the fusion for MPC treatment groups compared with CP. Biomechanical analyses
      were not able to differentiate between treatment groups. Histomorphometry results
      confirmed radiographic and quantitative computed tomography results; cell
      supplemented treatment groups and autograft had equivalent amounts of bone within
      the fusion mass and less bony fusion tissue was found within the fusion mass in
      specimens from the CP treatment group. No conclusive effects of cell dose of
      fusion efficacy were noted. CONCLUSIONS: Adult allogeneic mesenchymal precursor
      cells delivered via a hydroxyapatite:tricalcium phosphate carrier were both safe
      and efficacious in this ovine spine fusion model. Results from this preclinical
      study support that allogeneic mesenchymal precursor cells produced fusion
      efficacy similar to that achieved using iliac crest autograft, thereby providing
      a safe and viable option to achieve successful posterolateral spine fusion.

PMID- 24438942
TI  - Platelet microparticle generation assay for detection of HIT antibodies: advance,
      retreat, or too soon to tell?

PMID- 24438943
TI  - Microvascular platforms for the study of platelet-vessel wall interactions.
AB  - Platelets interact with the endothelium to regulate vascular integrity and
      barrier function, mediate inflammation and immune response, and prevent and
      arrest hemorrhage. In this review, we describe existing tools to study the flow
      dependent interactions of platelets with the vessel wall. We also discuss our
      work on building engineered microvessels to study the roles of platelets on
      endothelial barrier function, endothelial sprouting, and thrombus formation on
      both quiescent and stimulated endothelium. In particular, we will show the
      advantage of using a cell-remodelable system in the studies of platelet-vessel
      wall interactions. 

PMID- 24438944
TI  - Thyroid function, activated protein C resistance and the risk of venous
      thrombosis in users of hormonal contraceptives.
AB  - INTRODUCTION: Use of combined hormonal contraceptives is associated with a three-
      to eight-fold increased risk of venous thrombosis compared with non-use. The
      thrombotic risk depends on the estrogen dose as well as the progestogen type. Use
      of hormonal contraceptives leads to resistance to activated protein C (APC),
      which may serve as marker for the risk of venous thrombosis. Hyperthyroidism is
      also associated with an increased risk of venous thrombosis, due to increased
      free Thyroxine (FT4) levels which cause a hypercoagulable state. MATERIALS AND
      METHODS: The objective of this study was to evaluate the effects of hormonal
      contraceptives on levels of FT4, thyroid stimulating hormone (TSH) and thyroxine
      binding globulin (TBG), and to investigate the effects on APC resistance per
      contraceptive group. We measured FT4, TBG and TSH levels and APC resistance in
      231 users of oral contraceptives. RESULTS: Users of the most thrombogenic
      hormonal contraceptives, i.e. containing desogestrel, cyproterone acetate or
      drospirenone, had higher TBG levels than users of less thrombogenic hormonal
      contraceptives, i.e. the levonorgestrel-containing intrauterine device. TSH
      levels were not significantly elevated and FT4 levels did not change. TBG levels
      were also associated with APC resistance. CONCLUSION: Use of hormonal
      contraceptives lead to elevated TBG levels, slightly elevated TSH levels and
      unchanged FT4 levels without causing a hyperthyroid state. Thus, the increased
      thrombotic risk during the use of hormonal contraceptives cannot be explained by
      a hyperthyroid state caused by use of these hormonal contraceptives.

PMID- 24438941
TI  - D-dimer levels and 90-day outcome in patients with acute pulmonary embolism with
      or without cancer.
AB  - BACKGROUND: The prognostic value of D-dimer testing in patients with acute
      pulmonary embolism (PE) has not been thoroughly studied. METHODS: We used the
      RIETE Registry data to assess the 90-day prognostic value of increased IL Test D
      dimer levels at baseline in patients with PE, according to the presence or
      absence of cancer. RESULTS: As of May 2013, 3,283 patients with acute PE
      underwent D-dimer testing using IL Test D-dimer. Among 2,588 patients without
      cancer, those with D-dimer levels in the highest quartile had a higher rate of
      fatal PE (2.6% vs. 0.9%; p=0.002), fatal bleeding (1.1% vs. 0.3%; p=0.017) and
      all-cause death (9.1% vs. 4.4%; p<0.001) at 90 days compared with those with
      levels in the lowest quartiles. Among 695 patients with cancer, those with levels
      in the highest quartile had a similar rate of fatal PE or fatal bleeding but
      higher mortality (35% vs. 24%; p<0.01). On multivariate analysis, non-cancer
      patients with D-dimer levels in the highest quartile had an increased risk for
      fatal PE (odds ratio [OR]: 3.3; 95% CI: 1.6-6.6), fatal bleeding (OR: 4.3; 95%
      CI: 1.4-13.7) and all-cause death (OR: 2.1; 95% CI: 1.4-3.1) compared with
      patients with levels in the lowest quartiles. CONCLUSIONS: Non-cancer patients
      with acute PE and IL Test D-dimer levels in the highest quartile had an
      independently higher risk for fatal PE, fatal bleeding and all-cause death at 90
      days than those with levels in the lowest quartiles. In patients with cancer, D
      dimer levels failed to predict fatal PE or fatal bleeding.

PMID- 24438945
TI  - MiR-150 enhances the motility of EPCs in vitro and promotes EPCs homing and
      thrombus resolving in vivo.
AB  - INTRODUCTION: Deep venous thrombosis (DVT) is one of the common peripheral
      vascular diseases. The recruitment and migration of bone marrow-derived
      endothelial progenitor cells (EPCs) to the sites of venous thrombus are necessary
      in the process of thrombus organization and recanalization. Our objective was to
      investigate the functional role of miR-150 in rat EPCs and its potential
      application in deep venous thrombosis. MATERIALS AND METHODS: Rat EPCs were
      cultured and transfected with miR-150 mimics and inhibitor. Wound healing assay,
      transwell migration assay and matrigel tube formation assay were performed to
      elucidate the effect of miR-150 of rat EPCs. Lentiviral construct expressing miR
      150 was transfected into EPCs and the EPCs were injected to rat models of DVT.
      The rats were sacrificed on the day of 7 and 14 after the transplantation and the
      histological study was performed. Luciferase reporter assay and Western blot were
      performed to evaluate rat miR-150 regulates the expression of c-Myb. RESULTS: MiR
      150 significantly promoted the migration and tube formation ability of EPCs in
      vitro and enhanced EPCs' homing, organization and resolution ability in vivo.
      Overexpression of miR-150 significantly reduced the protein level of c-Myb and
      repressed the activity of a luciferase reporter containing both of the two
      predicted miR-150 binding sites in c-Myb 3'-UTR, indicating that c-Myb may be a
      miR-150 target gene. CONCLUSION: MiR-150 enhanced the migration, tube formation,
      homing, thrombus recanalization and resolution ability of rat EPCs. Restoring miR
      150 in EPCs revealed potential application in DVT therapy.

PMID- 24438946
TI  - Co-administration of low molecular weight heparin enhances the profibrinolytic
      effect of warfarin through different mechanisms.
AB  - BACKGROUND AND OBJECTIVE: Treatment with vitamin K antagonists (VKA) reduces
      fibrinolytic resistance through the inhibition of thrombin-mediated activation of
      thrombin activatable fibrinolysis inhibitor (TAFI). Because low-molecular weight
      heparin (LMWH) is co-administered with VKA during initiation of anticoagulant
      treatment, we evaluated the effect of dual anticoagulation on fibrinolytic
      resistance. PATIENTS AND METHODS: Two groups of patients were studied: 1)
      patients on stable warfarin; 2) patients starting oral anticoagulant therapy, who
      were evaluated during dual anticoagulation and after enoxaparin withdrawal. Only
      samples with an INR between 2 and 3 were compared. The resistance of clots to t
      PA-induced fibrinolysis was evaluated in blood and plasma by thromboelastography
      (TEG) and turbidimetry, respectively. RESULTS: In patients on dual
      anticoagulation, blood fibrinolysis time (TEG) was significantly shorter than in
      patients on warfarin alone and significantly correlated with LMWH level. The
      profibrinolytic effect was partly ascribable to a reduction of thrombin-dependent
      TAFI activation: 1) thrombin and TAFIa generation were significantly reduced by
      dual anticoagulation; 2) the addition of enoxaparin to warfarin-blood reduced
      TAFI-mediated fibrinolysis inhibition. Patients on dual anticoagulation also
      displayed a reduction in clot strength, a phenomenon known to reduce fibrinolytic
      resistance. The profibrinolytic effect of LMWH co-administration was not seen in
      plasma, likely because TAFIa generation was below the threshold required to
      inhibit fibrinolysis. CONCLUSIONS: Co-administration of LMWH in patients under
      VKA reduces the fibrinolytic resistance of blood clots via TAFI-dependent and
      TAFI-independent mechanisms. Further studies are warranted to assess the clinical
      implications of these findings.

PMID- 24438950
TI  - Language barriers to informed consent for dermatologic interventions.

PMID- 24438951
TI  - Systematic review of randomized controlled trials on interventions for melasma:
      an abridged Cochrane review.
AB  - BACKGROUND: Multiple treatments exist for melasma; they are often substandard and
      associated with side effects. OBJECTIVES: We sought to assess the effectiveness
      of interventions used in the management of all types of melasma. METHODS: We
      undertook a systematic review using the methodology of the Cochrane
      Collaboration. RESULTS: We included 20 studies with a total of 2125 participants
      covering 23 different treatments. A meta-analysis was not possible because of the
      heterogeneity of treatments. Triple-combination cream (hydroquinone, tretinoin,
      and fluocinolone acetonide) was more effective at lightening melasma than
      hydroquinone alone (relative risk 1.58, 95% confidence interval 1.26-1.97) or any
      of the agents in a dual-combination cream. Azelaic acid (20%) was significantly
      more effective than 2% hydroquinone (relative risk 1.25, 95% confidence interval
      1.06-1.48) at lightening melasma. In 2 studies where tretinoin was compared with
      placebo, objective measures demonstrated significant reductions in the severity.
      However, only in 1 study did participants rate a significant improvement
      (relative risk 13, 95% confidence interval 1.88-89.74). LIMITATIONS: There was
      poor methodology, a lack of standardized outcome assessments, and short duration
      of studies. CONCLUSIONS: The current limited evidence supports the efficacy of
      multiple interventions. Randomized controlled trials on well-defined participants
      with long-term outcomes are needed.

PMID- 24438952
TI  - Large-cell transformation of mycosis fungoides-differential diagnosis with
      implications for clinical management: a consensus statement of the US Cutaneous
      Lymphoma Consortium.

PMID- 24438953
TI  - Keep on "Liking" us: the JAAD's Facebook page turns 2 years old.

PMID- 24438954
TI  - Point: Major adverse cardiovascular events and anti-IL 12/23 agents.

PMID- 24438955
TI  - Counterpoint: A tale of two meta-analyses revisited.

PMID- 24438956
TI  - Liposuction for axillary hyperhidrosis: reconciling trial results and expert
      opinion.

PMID- 24438957
TI  - Male genital edema in Crohn's disease.

PMID- 24438958
TI  - Tumor recurrence after Mohs micrographic surgery.

PMID- 24438959
TI  - Reply: Genital edema in Crohn's disease.

PMID- 24438960
TI  - Surgeon error and slide quality during Mohs micrographic surgery: is there a
      relationship with tumor recurrence?

PMID- 24438961
TI  - High survival rate of harlequin ichthyosis in Japan.

PMID- 24438962
TI  - Generational gap regarding patients' driving habits.

PMID- 24438963
TI  - Retronychia in children, adolescents, and young adults: a case series.

PMID- 24438964
TI  - Pruritus severity in patients with psoriasis is not correlated with psoriasis
      disease severity.

PMID- 24438965
TI  - Treatment of erythropoietic protoporphyria with the oral sorbent colestipol: a
      proof-of-concept clinical trial.

PMID- 24438966
TI  - JAAD grand rounds quiz. Hand ischemia in a hemodialysis patient.

PMID- 24438967
TI  - JAAD grand rounds quiz. Onychomatricoma.

PMID- 24438968
TI  - JAAD grand rounds quiz. Multiple papulonodules on the face and scalp.

PMID- 24438969
TI  - Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome): part
      I. Diagnosis: clinical and histopathologic features and new molecular and
      biologic markers.
AB  - Mycosis fungoides (MF) and Sezary syndrome (SS) comprise approximately 53% of
      cutaneous lymphomas. Both MF and SS may clinically and histologically mimic
      benign skin conditions, posing a diagnostic challenge to the dermatologist.
      Precise clinicopathologic correlation is necessary to support a diagnosis,
      especially in the early stages of disease. In addition to the identification of
      histopathologic criteria, ancillary studies, including the identification of
      CD4(+) T cells with aberrant immunophenotypes and T-cell receptor gene
      rearrangements within skin lesions and peripheral blood are used to support the
      diagnosis. Recent studies evaluating the pathogenesis of MF have found that the
      skin microenvironment, including immune cells, such as dendritic cells and
      reactive cytotoxic and regulatory T cells, plays a crucial supporting role in MF.
      The skin-homing ability of malignant T cells is the result of chemokines,
      cytokines, adhesion molecules, and defective apoptosis, and is believed to play a
      role in disease pathogenesis and progression. In addition, recent studies have
      also suggested that MF and SS arise from distinct memory T cell subsets and
      advanced/erythrodermic MF and SS may be distinguished by identification of
      certain molecules, including Programmed-Death-1. 

PMID- 24438973
TI  - Dermoscopy and the negative pigment network.

PMID- 24438970
TI  - Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome): part
      II. Prognosis, management, and future directions.
AB  - Both mycosis fungoides (MF) and Sezary syndrome (SS) have a chronic, relapsing
      course, with patients frequently undergoing multiple, consecutive therapies.
      Treatment is aimed at the clearance of skin disease, the minimization of
      recurrence, the prevention of disease progression, and the preservation of
      quality of life. Other important considerations are symptom severity, including
      pruritus and patient age/comorbidities. In general, for limited patch and plaque
      disease, patients have excellent prognosis on >=1 topical formulations, including
      topical corticosteroids and nitrogen mustard, with widespread patch/plaque
      disease often requiring phototherapy. In refractory early stage MF, transformed
      MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose
      immunomodulators (eg, interferon or bexarotene) may be effective. Patients with
      advanced and erythrodermic MF/SS can have profound immunosuppression, with
      treatments targeting tumor cells aimed for immune reconstitution. Biologic agents
      or targeted therapies either alone or in combination--including immunomodulators
      and histone-deacetylase inhibitors--are tried first, with more immunosuppressive
      therapies, such as alemtuzumab or chemotherapy, being generally reserved for
      refractory or rapidly progressive disease or extensive lymph node and metastatic
      involvement. Recently, an increased understanding of the pathogenesis of MF and
      SS with identification of important molecular markers has led to the development
      of new targeted therapies that are currently being explored in clinical trials in
      advanced MF and SS.

PMID- 24438974
TI  - Early detection of melanoma arising within nevus spilus.

PMID- 24438975
TI  - Dermoscopic "signature" pattern of pigmented and nonpigmented lentigo maligna.

PMID- 24438976
TI  - Rebound erythema and burning sensation from a new topical brimonidine tartrate
      gel 0.33%.

PMID- 24438977
TI  - Acne fulminans successfully treated with cyclosporine and isotretinoin.

PMID- 24438978
TI  - Complete pathologic response after neoadjuvant treatment with vemurafenib for
      malignant melanoma.

PMID- 24438979
TI  - Nonuremic calciphylaxis in a patient with rheumatoid arthritis and osteoporosis
      treated with teriparatide.

PMID- 24438980
TI  - Alcohol-induced vasculitis: case report and commentary.

PMID- 24438981
TI  - Carney syndrome in a patient previously considered to have Peutz-Jeghers
      syndrome.

PMID- 24438982
TI  - Focal nail dystrophy in a cutaneous nerve distribution after trauma.

PMID- 24438983
TI  - Dermatomyositis associated with capecitabine in the setting of malignancy.

PMID- 24438984
TI  - Anatomic shoulder arthroplasty for treatment of proximal humerus malunions.
AB  - BACKGROUND: Malunion of proximal humeral fractures complicated by damage to the
      glenohumeral cartilage and injury to the joint capsule and rotator cuff can
      include treatment requiring anatomic shoulder arthroplasty. This study defines
      results and complications of this procedure and identifies factors associated
      with success or failure. METHODS: From 1976 to 2007, 109 patients underwent
      shoulder arthroplasty for proximal humerus malunions. Ninety-five met the
      criteria for analysis with a mean follow-up period of 9.2 years. Fracture types
      according to the Neer classification were two part in 20, three part in 37, four
      part in 31, and head splitting in 2, with 16 fracture-dislocations.
      Hemiarthroplasty was performed in 45 patients, with 50 undergoing total
      arthroplasty. RESULTS: Pain scores improved from 7.8 to 3.1 (P < .001). The mean
      active elevation and external rotation improved from 69 degrees  to 109 degrees 
      and from 8 degrees  and 39 degrees , respectively (P = .001). Of 31 patients with
      available radiographs, 20 had healed tuberosity osteotomies. Sixteen
      complications required 10 reoperations, including 6 of 9 patients with severe
      postoperative instability. There were 57 excellent or satisfactory results by use
      of the Neer rating. No patient, injury pattern, previous treatment, surgical, or
      radiologic variation was significantly associated with an increased risk of an
      unsatisfactory result, except for severe postoperative instability. Kaplan-Meier
      survivorship for reoperation, in 109 shoulders, was 94.8% (95% confidence
      interval, 90.5%-99.4%) at 5 years and 90.1% (95% confidence interval, 83.6%
      97.1%) at 10 and 15 years. CONCLUSION: Anatomic shoulder arthroplasty improves
      pain and motion. Surgery is complex. Tuberosity osteotomies often heal.
      Postoperative instability is the most common complication leading to reoperation
      and is usually associated with rotator cuff and shoulder capsule injury.

PMID- 24438985
TI  - Potentially pathogenic Escherichia coli in healthy, pasture-raised sheep on farms
      and at the abattoir in Brazil.
AB  - Sheep harbor pathogenic Escherichia coli, which may cause severe disease in
      humans. In this study, the prevalence of Shiga toxin-producing E. coli (STEC) and
      enteropathogenic E. coli (EPEC) was examined in sheep feces and carcasses on
      three farms and at an abattoir in Brazil. The isolates were further characterized
      for the presence of markers recently associated with disease in humans, to
      investigate their possible origin and role as food-borne pathogens. At the
      abattoir, 99 carcass samples yielded two STEC and 10 EPEC isolates while 101
      fecal samples yielded five EPEC and eight STEC isolates. On the other hand, on
      the farms, 202 samples yielded 44 STEC and eight EPEC isolates. The 77 isolates
      were typed by PFGE. Isolates with the same PFGE pattern and also those that were
      not restricted with XbaI were termed as "clones" (n=49). The isolates of any one
      clone mostly originated from the same sampling site. In addition, seven isolates
      encoded for novel Stx2 variants and five for Stx2e, the subtype related to
      porcine edema disease, which was for the first time isolated from sheep feces and
      carcasses. Also, three stx2-only isolates harbored genes of predicted Stx2
      variants that were formed by A and B subunits of different types including Stx2a
      and Stx2d. The EPEC isolates were heterogeneous, 21 (91.3%) of them possessing
      efa1, ehxA, lpfAO113 or paa genes associated with diarrhea in humans. Thus, using
      markers recently associated with disease, we have demonstrated that E. coli
      similar to those pathogenic for humans are present in the sheep intestinal
      microflora, particularly at the abattoir, underlining the potential for food
      borne transmission. 

PMID- 24438986
TI  - Characteristics of a foot-and-mouth disease virus with a partial VP1 G-H loop
      deletion in experimentally infected cattle.
AB  - Previous work in cattle illustrated the protective efficacy and negative marker
      potential of a A serotype foot-and-mouth disease virus (FMDV) vaccine prepared
      from a virus lacking a significant portion of the VP1 G-H loop (termed A(-)).
      Since this deletion also includes the arginine-glycine-aspartate (RGD) motif
      required for virus attachment to the host cell in vivo, it was hypothesised that
      this virus would be attentuated in naturally susceptible animals. The A(-) virus
      was passaged three times in cattle via needle inoculation of virus suspension
      delivered into the intradermal space of the tongue (intradermolingual: IDL).
      Included in the study were three direct contact cattle, two of which were used
      for the third cattle passage (by inoculation) after direct contact exposure for
      three days. Cattle were monitored for clinical signs and samples were collected
      for sequencing as well as antibody and viral genome detection by ELISA and qRT
      PCR. Following needle inoculation with the A(-) virus, naive cattle developed
      typical clinical signs of FMDV infection, diagnostic assays also provided
      positive serological and virological results. However, the contact cattle did not
      develop clinical signs or generate serological or virological markers indicative
      of FMDV infection even when the cattle were subsequently needle inoculated with
      10(5) TCID50 A(-) FMDV delivered IDL following three days of direct contact
      exposure. The results suggest that the A(-) virus is not attentuated in cattle
      when inoculated IDL. This virus could be useful as a tool to understand further
      the natural pathogenesis, receptor usage and internalisation pathways of FMDV. 

PMID- 24438987
TI  - Staphylococcus warneri, a resident skin commensal of rainbow trout (Oncorhynchus
      mykiss) with pathobiont characteristics.
AB  - Commensal microorganisms live in association with the mucosal surfaces of all
      vertebrates. The skin of teleost fish is known to harbor commensals. In this
      study we report for the first time the presence of an intracellular Gram positive
      bacteria, Staphylococcus warneri that resides in the skin epidermis of rainbow
      trout (Oncorhynchus mykiss). S. warneri was isolated from healthy hatchery trout
      skin epithelial cells. In situ hybridization confirmed the intracellular nature
      of the bacterium. Skin explants exposed in vitro to S. warneri or the
      extracellular pathogen Vibrio anguillarum show that S. warneri is able to induce
      an anti-inflammatory cytokine status via TGF-beta1b compared to the pro
      inflammatory responses (IL-1beta, IL-6 and TNF-?) elicited by V. anguillarum. In
      vivo experiments showed that S. warneri is not pathogenic to rainbow trout when
      injected intraperitoneally at high concentrations. However, S. warneri is able to
      stimulate V. anguillarum growth and biofilm formation on rainbow trout scales.
      Our results demonstrate that rainbow trout skin commensals such as S. warneri
      have the potential to become indirect pathobionts by enhancing growth and biofilm
      formation of pathogens such as V. anguillarum. These results show that fish
      farming practices (i.e. handling and other manipulations) can alter the skin
      microbiota and compromise the skin health of rainbow trout.

PMID- 24438992
TI  - Analysis of parameters for the automatic computation of the tear film break-up
      time test based on CCLRU standards.
AB  - Dry eye syndrome is affecting a remarkable percentage of population. The
      prevalence is 10-15% of normal population, and 18-30% of contact lenses users.
      The break-up time (BUT) is a clinical test used for the diagnosis of this
      disease. In this work, we perform an analysis of parameters for a global and a
      local automatic computation of the BUT measure, based on criteria of specificity
      and sensitivity. We have tested our methodology on a dataset composed of 18
      videos annotated by 4 different experts. The local analysis preserves the results
      of the global approach providing useful additional information about the break-up
      tear zone. 

PMID- 24438993
TI  - Hand gesture guided robot-assisted surgery based on a direct augmented reality
      interface.
AB  - Radiofrequency (RF) ablation is a good alternative to hepatic resection for
      treatment of liver tumors. However, accurate needle insertion requires precise
      hand-eye coordination and is also affected by the difficulty of RF needle
      navigation. This paper proposes a cooperative surgical robot system, guided by
      hand gestures and supported by an augmented reality (AR)-based surgical field,
      for robot-assisted percutaneous treatment. It establishes a robot-assisted
      natural AR guidance mechanism that incorporates the advantages of the following
      three aspects: AR visual guidance information, surgeon's experiences and accuracy
      of robotic surgery. A projector-based AR environment is directly overlaid on a
      patient to display preoperative and intraoperative information, while a mobile
      surgical robot system implements specified RF needle insertion plans. Natural
      hand gestures are used as an intuitive and robust method to interact with both
      the AR system and surgical robot. The proposed system was evaluated on a
      mannequin model. Experimental results demonstrated that hand gesture guidance was
      able to effectively guide the surgical robot, and the robot-assisted
      implementation was found to improve the accuracy of needle insertion. This human
      robot cooperative mechanism is a promising approach for precise transcutaneous
      ablation therapy. 

PMID- 24439000
TI  - Hippocampal and orbital inferior frontal gray matter volume abnormalities and
      cognitive deficit in treatment-naive, first-episode patients with schizophrenia.
AB  - BACKGROUND: Cognitive impairment is a core feature of schizophrenia. Some
      evidence suggests an association between cognition deficits and gray matter
      reductions. In this study, we investigated the relationship between cognitive
      performance and gray matter volumes in patients with treatment-naive, first
      episode schizophrenia. METHOD: First-episode patients with treatment-naive
      schizophrenia and healthy controls went through brain imaging scan using high
      resolution magnetic resonance imaging. A neuropsychological battery including 8
      neurocognitive tests was used to assess cognitive function. Voxel-based methods
      were used for volumetric measure in the brain. RESULTS: Fifty-one patients and 41
      healthy controls were included in the analysis. Patients exhibited a poorer
      performance on all 7 cognitive function tests compared with healthy controls
      (ps<0.006). There were significant gray matter volume differences between the two
      groups in bilateral hippocampus gyri, right superior temporal gyrus, left
      fusiform gyrus and orbital inferior frontal gyri (FDR, ps<0.05). Within the
      schizophrenia group, multiple regression analysis demonstrated that poorer
      performance on the working memory, verbal learning and visual learning was
      associated with smaller hippocampal gray matter volume, and poorer executive
      function was associated with smaller left orbital inferior frontal gray matter
      volume after controlling for potential confounding variables (beta >= 0.420, ps
      <= 0.010). CONCLUSIONS: Our findings suggest that cognitive deficits are
      associated with hippocampal and orbital inferior frontal gray matter volume
      abnormalities in treatment-naive, first-episode patients with schizophrenia.

PMID- 24438999
TI  - Reducing youth internalizing symptoms: effects of a family-based preventive
      intervention on parental guilt induction and youth cognitive style.
AB  - This study utilized structural equation modeling to examine the associations
      among parental guilt induction (a form of psychological control), youth cognitive
      style, and youth internalizing symptoms, with parents and youth participating in
      a randomized controlled trial of a family-based group cognitive-behavioral
      preventive intervention targeting families with a history of caregiver
      depression. The authors present separate models utilizing parent report and youth
      report of internalizing symptoms. Findings suggest that families in the active
      condition (family-based group cognitive-behavioral group) relative to the
      comparison condition showed a significant decline in parent use of guilt
      induction at the conclusion of the intervention (6 months postbaseline).
      Furthermore, reductions in parental guilt induction at 6 months were associated
      with significantly lower levels of youth negative cognitive style at 12 months.
      Finally, reductions in parental use of guilt induction were associated with lower
      youth internalizing symptoms 1 year following the conclusion of the intervention
      (18 months postbaseline).

PMID- 24439010
TI  - Editorial comment.

PMID- 24439009
TI  - Probability of an abnormal screening prostate-specific antigen result based on
      age, race, and prostate-specific antigen threshold.
AB  - OBJECTIVE: To determine the distribution of screening prostate-specific antigen
      (PSA) values in older men, and how different PSA thresholds affect the proportion
      of white, black, and Latino men who would have an abnormal screening result
      across advancing age groups. METHODS: We used linked national Veterans Affairs
      and Medicare data to determine the value of the first screening PSA test (ng/mL)
      of 327,284 men older than 65 years who underwent PSA screening in the Veterans
      Affairs health care system in 2003. We calculated the proportion of men with an
      abnormal PSA result based on age, race, and common PSA thresholds. RESULTS: Among
      men older than 65 years, 8.4% had a PSA >4.0 ng/mL. The percentage of men with a
      PSA >4.0 ng/mL increased with age and was highest in black men (13.8%) vs white
      (8.0%) or Latino men (10.0%) (P <.001). Combining age and race, the probability
      of having a PSA >4.0 ng/mL ranged from 5.1% of Latino men aged 65-69 years to
      27.4% of black men older than 85 years. Raising the PSA threshold from >4.0 ng/mL
      to >10.0 ng/mL reclassified the greatest percentage of black men older than 85
      years (18.3% absolute change) and the lowest percentage of Latino men aged 65-69
      years (4.8% absolute change) as being under the biopsy threshold (P <.001).
      CONCLUSION: Age, race, and PSA threshold together affect the pretest probability
      of an abnormal screening PSA result. Based on screening PSA distributions,
      stopping screening among men whose PSA <3 ng/mL means more than 80% of white and
      Latino men older than 70 years would stop further screening, and increasing the
      biopsy threshold to >10 ng/mL has the greatest effect on reducing the number of
      older black men who will face biopsy decisions after screening.

PMID- 24439012
TI  - Assessing protection against radiation exposure after prostate (125)I
      brachytherapy.
AB  - PURPOSE: To expand the radiation dose rate measurement data set by measuring
      radiation under various prostate (125)I brachytherapy situations. METHODS AND
      MATERIALS: Measurements were obtained from 63 consecutive unselected patients at
      Tokyo Medical Center, Japan. Differences in factors during measurements, such as
      body postures, distances from the skin surface, and measurement directions were
      considered. Furthermore, shielding effects of lead-lined underwear, consisting
      mainly of 0.1-mm thickness of lead, were also assessed. RESULTS: Radiation
      exposure varies according to the patient's body posture, with results differing
      as much as approximately 40.0% in measured radiation dose rates at 30cm from the
      anterior skin surface. Weight, body mass index, and tissue thickness showed good
      correlations with measured radiation dose rates. The magnitude of radiation
      exposure attenuation by shielding was approximately 95.8%, similar to the
      attenuation ratio based on tissue measurements made in the lateral direction. The
      respective mean times required to reach 1mSv were 1.2, 7.6, and 65.4 days in the
      standing position and 0.6, 4.6, and 40.4 days in the supine position at the site
      of contact, and at 30 and 100cm from the anterior skin surface. CONCLUSIONS: This
      study obtained supplemental information pertaining to radiological protection and
      confirmed that shielding can be an effective tool for reducing exposures.

PMID- 24439013
TI  - Differences in acoustic and perceptual parameters of the voice between elderly
      and young women at habitual and high intensity.
AB  - INTRODUCTION AND OBJECTIVES: The present study aimed to compare elderly and young
      female voices in habitual and high intensity. The effect of increased intensity
      on the acoustic and perceptual parameters was assessed. METHODS: Sound pressure
      level, fundamental frequency, jitter, shimmer, and harmonic to noise ratio were
      obtained at habitual and high intensity voice in a group of 30 elderly women and
      30 young women. Perceptual assessment was also performed. RESULTS: Both groups
      demonstrated an increase in sound pressure level and fundamental frequency from
      habitual voice to high intensity voice. No differences were found between groups
      in any acoustic variables on samples recorded with habitual intensity level. No
      significant differences between groups were found in habitual intensity level for
      pitch, hoarseness, roughness, and breathiness. Asthenia and instability obtained
      significant higher values in elderly than young participants, whereas, the
      elderly demonstrated lower values for perceived tension and loudness than young
      subjects. CONCLUSIONS: Acoustic and perceptual measures do not demonstrate
      evident differences between elderly and young speakers in habitual intensity
      level. The parameters analyzed may lack the sensitivity necessary to detect
      differences in subjects with normal voices. Phonation with high intensity
      highlights differences between groups, especially in perceptual parameters.
      Therefore, high intensity should be included to compare elderly and young voice.

PMID- 24439022
TI  - Feeding soybean meal increases the blood level of isoflavones and reduces the
      steroidogenic capacity in bovine corpora lutea, without affecting peripheral
      progesterone concentrations.
AB  - Thirty-three Holstein-Friesian cows were followed from 14 days pre partum until
      the fourth ovulation post partum. Housing conditions and basic ration were
      identical for all animals. Concentrates were individually supplemented according
      to the daily milk production level, using two different types of protein rich
      concentrates: soybean meal and rapeseed meal. Soybean and rapeseed meal are known
      to be respectively high and low in isoflavones. Cows were randomly divided into
      three groups and blocked for parity. Group I (n=11) was supplemented with soybean
      meal and acted as control group. Groups II (n=11) and III (n=11) were
      respectively supplemented with soybean and rapeseed meal and were subjected to a
      biopsy sampling of the corpus luteum at day 9 of the first three postpartal
      estrous cycles. Soybean meal supplementation to lactating dairy cows (1.72 kg on
      average) induced an increase in the blood concentration of equol,
      dihydrodaidzein, o-desmethylangolensin in both soy groups and resulted in a
      reduced area occupied by steroidogenic (P=0.012) and endothelial cells (P=0.0007)
      in the luteal biopsies. Blood concentrations of equol and glycitein were
      negatively correlated with the areas occupied by steroidogenic (r=-0.410 with
      P=0.0002, respectively r=-0.351 with P=0.008) and endothelial cells (r=-0.337
      with P=0.01, respectively r=-0.233 with P=0.085) in the 3 first estrous cycles.
      The latter however did not affect the diestrous peripheral blood progesterone
      concentration.

PMID- 24439023
TI  - Detection of estrous behavior in buffalo heifers by radiotelemetry following
      PGF2alpha administration during the early or late luteal phase.
AB  - This study examined the usefulness of radiotelemetry for estrous detection in
      buffalo heifers and the impact of prostaglandin F2alpha (PGF2alpha)
      administration during the early or late luteal phase on estrous behavior and
      ovulatory follicle variables. Induction of estrus with PGF2alpha at a random
      stage of the estrous cycle was followed by the arbitrary division of heifers into
      groups receiving a second dose of PGF2alpha during either the early (n=33) or
      late (n=17) luteal phase (6-9 or 11-14 days after estrus, respectively) for the
      induction of synchronized estrus. The electronic detection of synchronized estrus
      by radiotelemetry was confirmed using ultrasonography every 6h until ovulation.
      Radiotelemetry was 90% efficient and 100% accurate for estrous detection.
      Intervals between the PGF2alpha dose and the beginning of synchronized estrus
      (40.7 +/- 10.9 vs. 56.7 +/- 12.8h) or ovulation (70.0 +/- 11.3 vs. 85.6 +/-
      12.5h) were shorter (P<0.05) for heifers receiving PGF2alpha during the early
      luteal phase. PGF2alpha administration during the early or late luteal phase
      produced similar (P>0.05) results for the duration of estrus, the intervals from
      the beginning or end of estrus to ovulation, the number and duration of mounts
      per estrus, the duration of mounts, the diameter of the ovulatory follicle and
      the luteal profile on day 5 after estrus. In conclusion, radiotelemetry was a
      suitable tool for the efficient and accurate detection of estrus in buffalo
      heifers. Treatment with PGF2alpha during the early luteal phase had a shorter
      interval to synchronized estrus and ovulation; however, estrous behavior,
      ovulatory follicle dynamics and subsequent luteal activity were similar following
      PGF2alpha administration during the early or late luteal phase.

PMID- 24439024
TI  - Knockdown of the germ cell factor Dead end induces multiple transcriptional
      changes in Atlantic cod (Gadus morhua) hatchlings.
AB  - The RNA binding protein Dead end (DnD) is essential for maintaining viable germ
      cells in vertebrates and silencing of the gene has been demonstrated to cause
      sterility in several mammalian and fish species. Here we investigated
      transcriptome changes in hatched larvae of Atlantic cod induced by DnD knockdown
      using morpholino oligonucleotides (MO) injected in two-cell embryos. Whereas no
      fluorescently labeled germ cells were shown in embryos coinjected with dnd MO and
      nanos3 3'UTR coupled to green fluorescent protein, DnD knockdown had no visible
      effect on the number and location of Vasa protein positive cells in larvae.
      However, quantitative real-time RT-PCR (qPCR) revealed decreased vasa, nanos3 and
      tudor domain containing protein 7 mRNA expression and genome-wide oligonucleotide
      microarray analyses indicated profound suppression of genes involved in
      development and regulation of the reproductive system. DnD morphants showed
      lowered expression of genes encoding proteins involved in lipid, retinoid,
      cholesterol and steroid metabolism, including those with roles in sex hormone
      metabolism. Biotransformation of lipophilic compounds appeared suppressed too, as
      evidenced by down-regulation of several key genes from the phases 1 and 2
      detoxification pathways. Effects of DnD silencing were highly pleiotropic and
      consisted of endocrine and metabolic changes, massive induction of histones and
      suppression of diverse developmental processes, including erythropoiesis and
      formation of extracellular matrix. While transient inhibition of dnd mRNA
      translation did not block development of primordial germ cells until hatch,
      results suggested that ablation of DnD might have major indirect consequences,
      including suppression of reproductive functions. 

PMID- 24439025
TI  - Blue-green algal blooms have been documented since the 12th century. Foreword.

PMID- 24439026
TI  - Freshwater harmful algal blooms: toxins and children's health.
AB  - Massive accumulations of cyanobacteria (a.k.a. "blue-green algae"), known as
      freshwater harmful algal blooms (FHABs), are a common global occurrence in water
      bodies used for recreational purposes and drinking water purification. Bloom
      prevalence is increased due to anthropogenic changes in land use, agricultural
      activity, and climate change. These photosynthetic bacteria produce a range of
      toxic secondary metabolites that affect animals and humans at both chronic and
      acute dosages. Children are especially at risk because of their lower body
      weight, behavior, and toxic effects on development. Here we review common FHAB
      toxins, related clinical symptoms, acceptable concentrations in drinking water,
      case studies of children's and young adults' exposures to FHAB toxins through
      drinking water and food, methods of environmental and clinical detection in
      potential cases of intoxication, and best practices for FHAB prevention. 

PMID- 24439027
TI  - The case for addressing primary resistance mutations to non-nucleoside reverse
      transcriptase inhibitors to treat children born from mothers living with HIV in
      sub-Saharan Africa.
AB  - The prevalence of human immunodeficiency virus (HIV) drug resistance mutations
      (DRMs) was estimated in 25 untreated infants who were living with HIV-1, younger
      than 13 months and living in Senegal. Antiretroviral DRMs were detected in 8 of
      25 (32%) children. Non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs
      were present in all (100%) children whose viruses harboured DRMs: K103N in 43%;
      Y181C, K101E and V106M each in 29%; and Y188L in 14%. The D67N thymidine-analogue
      mutation was observed in only two children whose mothers had received
      chemoprophylaxis of mother-to-child transmission (MTCT). The proportion of
      children whose viruses harboured DRMs was then 6.5-fold higher in children whose
      mother-child couples had received nevirapine (NVP)-based chemoprophylaxis than in
      other couples without prophylaxis [7 of 13 (53.8%) vs. 1 of 12 (8.3%)]. These
      findings point to the absolute need to address primary resistance mutations in
      case of virological failure in young children treated by antiretroviral drugs,
      and to make more effective treatment regimens available to NVP-exposed infants
      living with HIV-1 in Senegal. 

PMID- 24439029
TI  - Extravillous trophoblast cell invasion is promoted by the CD44-hyaluronic acid
      interaction.
AB  - INTRODUCTION: Extravillous trophoblast (EVT) cell invasion plays a crucial role
      in establishment of successful pregnancy. CD44, a cell-surface receptor for
      hyaluronic acid (HA), plays a key role in HA-mediated remodeling and degradation
      that triggers cancer cell invasion. However, few studies have reported on the
      expression or functions of CD44 in human EVT cells. We hypothesized that CD44-HA
      interaction was involved in invasion by EVT cells. METHODS: To test our
      hypothesis, we conducted in situ examinations of CD44 and HA expression in the
      human first-trimester placenta. We also assessed the methylation status of CD44
      promoter and exon 1 regions in EVT cells. Finally, we conducted transwell cell
      invasion assays using EVT cell lines and EVT cells isolated from first-trimester
      human villous explant cultures. RESULTS AND DISCUSSION: EVT cells, but not
      villous trophoblast cells, in the first-trimester placenta expressed CD44. HA was
      strongly expressed in adventitia surrounding the spiral uterine arterial walls of
      the decidua. The extent of demethylation of CD44 promoter and exon 1 CpG islands
      was increased in EVT cells compared to those of first-trimester chorionic villi
      (including villous trophoblast cells), suggesting that CD44 expression was, at
      least in part, associated with methylation status. Data from transwell cell
      invasion assay with siRNA knockdown of CD44 revealed that CD44 expression
      significantly promoted invasion by EVT cells in an HA-dependent manner.
      CONCLUSIONS: The discovery of a CD44-HA interaction between EVT cells and the
      extracellular matrix contributes to our understanding of the mechanism underlying
      invasion by EVT cells.

PMID- 24439034
TI  - In search of the pivot point of mechanotransduction: mechanosensing of stem
      cells.
AB  - Stem cells are undifferentiated cells with the ability to self-renew and to
      differentiate into diverse specialized cell types; hence, they have great
      potential in tissue engineering and cell therapies. In addition to biochemical
      regulation, the physical properties of the microenvironments, such as scaffold
      topography, substrate stiffness, and mechanical forces, including fluid shear
      stress, compression, and tensile strain, can also regulate the proliferation and
      differentiation of stem cells. Upon physical stimuli, cytoskeleton rearrangements
      are expected to counterbalance the extracellular mechanical forces, trigger
      signaling cascades, and eventually cause epigenetic modifications. This article
      mainly focuses on the mechanosensing, which is the upstream event of stem cell
      mechanotransduction and the downstream one of physical stimuli. Putative
      mechanosensors such as ion channels, integrins, and cell membrane as well as
      primary cilia are discussed. Because mechanical environment is an important stem
      cell niche, identification of mechanosensors not only can elucidate the
      mechanisms of mechanotransduction and fate commitments but also bring new
      prospects of the mechanical control as well as drug development for clinical
      application. 

PMID- 24439028
TI  - Search for age-related macular degeneration risk variants in Alzheimer disease
      genes and pathways.
AB  - Several lines of inquiry point to overlapping molecular mechanisms between late
      onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We
      evaluated summarized results from large genome-wide association studies for AD
      and AMD to test the hypothesis that AD susceptibility loci are also associated
      with AMD. We observed association of both disorders with genes in a region of
      chromosome 7, including PILRA and ZCWPW1 (peak AMD SNP rs7792525, minor allele
      frequency [MAF] = 19%, odds ratio [OR] = 1.14, p = 2.34 * 10(-6)), and with ABCA7
      (peak AMD SNP rs3752228, MAF = 0.054, OR = 1.22, p = 0.00012). Next, we evaluated
      association of AMD with genes in AD-related pathways identified by canonical
      pathway analysis of AD-associated genes. Significant associations were observed
      with multiple previously identified AMD risk loci and 2 novel genes: HGS (peak
      SNP rs8070488, MAF = 0.23, OR = 0.91, p = 7.52 * 10(-5)), which plays a role in
      the clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590,
      MAF = 0.34, OR = 0.89, p = 1.17 * 10(-5)), which is a member of the
      atherosclerosis signaling and the LXR/RXR activation pathways. Our results
      suggest that AMD and AD share genetic mechanisms.

PMID- 24439035
TI  - Assessing the risk of highly pathogenic avian influenza H5N1 transmission through
      poultry movements in Bali, Indonesia.
AB  - Indonesia continues to report the highest number of human and poultry cases of
      highly pathogenic avian influenza H5N1. The disease is considered to be endemic
      on the island of Bali. Live bird markets are integral in the poultry supply chain
      on Bali and are important, nutritionally and culturally, for the rural and urban
      human populations. Due to the lack of biosecurity practiced along the supply
      chain from producer to live bird markets, there is a need to understand the risks
      associated with the spread of H5N1 through live bird movements for effective
      control. Resources to control H5N1 in Indonesia are very limited and cost
      effective strategies are needed. We assessed the probability a live bird market
      is infected through live poultry movements and assessed the effects of
      implementing two simple and low cost control measures on this risk. Results
      suggest there is a high risk a live bird market is infected (0.78), and risk
      mitigation strategies such as detecting and removing infected poultry from
      markets reduce this risk somewhat (range 0.67-0.76). The study demonstrates the
      key role live poultry movements play in transmitting H5N1 and the need to
      implement a variety of control measures to reduce disease spread. 

PMID- 24439036
TI  - Maternal depressive symptoms and sensitivity are related to young children's
      facial expression recognition: the Generation R Study.
AB  - A vast body of literature shows that maternal depression has long-term adverse
      consequences for children. However, only very few studies have documented the
      effect of maternal depression on children's ability to process emotional
      expressions and even fewer incorporated measures of observed maternal sensitivity
      to further tease apart whether it is the symptoms per se or the associated impact
      via maternal sensitivity that affects children's developing emotion-processing
      abilities. In a large community sample of Dutch preschoolers (N = 770), we
      examined independent and mediated effects of maternal depressive symptoms and
      sensitivity on children's ability to recognize emotional expressions using a
      nonverbal and a verbal task paradigm. Maternal depressive symptoms predicted less
      accurate emotion labeling in children, while maternal sensitivity was associated
      with more accurate emotion matching, especially for sadness and anger. Maternal
      sensitivity did not mediate the observed associations between mothers' depressive
      symptoms and children's emotion recognition, and effects were similar for boys
      and girls. Given that maternal depressive symptoms and sensitivity affected
      nonoverlapping areas of young children's emotion recognition, prevention and
      intervention efforts should focus on both alleviating maternal depressive
      symptoms and improving maternal sensitivity at the same time in order to maximize
      benefit.

PMID- 24439037
TI  - Women with alopecia exhibit a higher risk for thyroid cancer: a nationwide cohort
      study.
AB  - BACKGROUND: Several studies have investigated the relationship between alopecia
      and prostate cancer. However, little information is available regarding the
      relationship between alopecia and the risk of cancers in women. OBJECTIVE: The
      purpose of this study was to evaluate the possible association between alopecia
      and thyroid cancer among Taiwanese women. METHODS: We used data from the National
      Health Insurance system of Taiwan. The alopecia cohort comprised 4534 women, and
      each woman was randomly frequency matched by age, index month, and index year
      with 4 women from the general population without alopecia. A Cox proportional
      hazard regression analysis with Bonferroni correction was conducted to estimate
      the effects of alopecia on the risk of thyroid cancer. RESULTS: In women with
      alopecia, the overall risk for developing cancer was 22% higher than for subjects
      without alopecia, but the difference was not significant [hazard ratio (HR) =
      1.22, 97.5% confidence interval (97.5% CI) = 0.87-1.70]. However, the risk for
      developing thyroid cancer among women with alopecia was significantly higher (HR
      = 2.39, 97.5% CI = 1.05-5.42). Further analyses determined that the alopecia
      group had a higher incidence of Graves' disease, but not Hashimoto thyroiditis.
      CONCLUSION: Although alopecia did not significantly increase cancer risks in
      women, we found that Taiwanese women with alopecia had a higher risk of
      developing thyroid cancer that is unlikely to be related to underlying thyroid
      diseases.

PMID- 24439038
TI  - Krtap11-1, a hair keratin-associated protein, as a possible crucial element for
      the physical properties of hair shafts.
AB  - BACKGROUND: The physical properties of the hair are predominantly determined by
      the assembly of keratin bundles. The keratin-associated proteins (Krtaps) are
      thought to be involved in keratin bundle assembly, however, the functional role
      of the individual member still remains largely unknown. OBJECTIVE: The aim of
      this study is to clarify the role of a unique class of Krtaps, Krtap11-1, in the
      development and physical properties of the hair. METHODS: The expression
      regulation of Krtap11-1 was analyzed and its binding partners in the hair cortex
      were determined. Also, the effects of the forcible expression of this protein on
      the hair follicle development were analyzed in culture. RESULTS: The expression
      pattern of Krtap11-1 was concentrically asymmetric in the faulty hair that
      develops in Foxn1nu mice. In cultured keratinocytes, the expression of Krtap11-1
      transgene product was strictly regulated by the keratinization process and
      proteasome-dependent protein elimination. While the association with keratin as
      well as the cohesive self-assembly of Krtap11-1 appeared to be stabilized by
      disulfide cross-links, the biotinylated Krtap11-1 probe enabled the adherence to
      certain type I keratins in the hair cortex, including K31, 33 and 34, in the
      absence of disulfide formation. When embryonic upper lip rudiments were forcibly
      introduced with Krtap11-1, the hair follicles formed irregularly arranged
      globular hair keratin-clumps surrounded by multilayered epithelial cells in
      culture. CONCLUSION: Krtap11-1 may play an important role on keratin-bundle
      assembly in the hair cortex and this study provides insight into the physical
      properties of the hair shaft.

PMID- 24439040
TI  - Old and new methods of evaluating the ocular surface.

PMID- 24439041
TI  - Challenges in using signs and symptoms to evaluate new biomarkers of dry eye
      disease.

PMID- 24439042
TI  - Ocular surface concepts: development and citation.

PMID- 24439043
TI  - Rose bengal: the second most commonly used surfocular vital stain.

PMID- 24439044
TI  - S100A proteins as molecular targets in the ocular surface inflammatory diseases.
AB  - The S100 proteins are calcium-binding proteins that are exclusively expressed in
      vertebrates, where they interact with enzymes, cytoskeletal proteins, receptors,
      transcription factors, and nucleic acids to regulate proliferation,
      differentiation, apoptosis, inflammation, cell migration, energy metabolism, and
      Ca(2+) homeostasis. In this review, we focus on the S100A8 and S100A9 members of
      the family that are involved in the regulation of neutrophil chemotaxis and
      inflammation related to ocular surface diseases such as dry eye, meibomian gland
      dysfunction, pterygium, and corneal neovascularization. In our previous studies,
      we have found that the levels of S100A8 and S100A9 were elevated in these
      inflammatory ocular diseases. For instance, S100A8 and A9 were found to be
      upregulated in pterygium tissues at both transcript and protein levels. These
      findings are consistent with the role of S100A8 and S100A9 proteins in activating
      the innate immune system in the eye via Toll-like receptors (TLRs) and altering
      the immune tolerance of the eye-associated lymphoid system. Recently, use of
      S100A8-targeting antibody has shown promising results in targeting corneal
      neovascularization. Injection of S100A8 has been shown to inhibit eosinophilic
      infiltration and thus may have potential therapeutic implications in allergic
      diseases. 

PMID- 24439045
TI  - The role of corneal innervation in LASIK-induced neuropathic dry eye.
AB  - Almost half the patients who undergo laser in situ keratomileusis (LASIK)
      experience dry eye following the procedure. However, the etiology of LASIK
      induced dry eye is unclear. The purpose of this review is to examine and
      summarize the current evidence for the etiology of LASIK-induced dry eye, with a
      focus on ocular surface sensitivity and corneal innervation. Evidence suggests
      that the alteration of corneal nerves after LASIK is the most likely cause of the
      subjective symptoms of LASIK-induced dry eye, even though corneal sensitivity and
      the clinical indicators of dry eye return to apparently normal values within a
      year due to the partial recovery of the corneal nerve plexus. The hypothesis is
      explored that dry eye symptoms following LASIK may result from abnormal sensation
      due to LASIK-induced corneal neuropathy. Other factors, such as alterations in
      conjunctival goblet cell density, might also contribute to the symptoms and signs
      of LASIK-induced dry eye. Inter-relationships between nerve morphology, tear
      neuropeptide levels and dry eye require further investigation. A better
      understanding of this phenomenon may result in improved management of post-LASIK
      dry eye.

PMID- 24439046
TI  - Ultra high-resolution anterior segment optical coherence tomography in the
      diagnosis and management of ocular surface squamous neoplasia.
AB  - The development of optical coherence tomography (OCT) technology has helped to
      usher in a new era of in vivo diagnostic imaging of the eye. The utilization of
      OCT for imaging of the anterior segment and ocular surface has evolved from time
      domain devices to spectral-domain devices with greater penetrance and resolution,
      providing novel images of anterior segment pathology to assist in diagnosis and
      management of disease. Ocular surface squamous neoplasia (OSSN) is one such
      pathology that has proven demonstrable by certain anterior segment OCT machines,
      specifically the newer devices capable of performing ultra high-resolution OCT
      (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for
      diagnosis and differentiation from other ocular surface pathologies. Subtle
      findings on these images help to characterize the OSSN lesions beyond what is
      apparent with the clinical examination, providing guidance for clinical
      management. The purpose of this review is to examine the published literature on
      the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as
      to report novel uses of this technology and potential directions for its future
      development.

PMID- 24439048
TI  - Risk of skin cancer in patients with pterygium: a nationwide population-based
      cohort study in Taiwan.
AB  - This study investigated the association between pterygium and skin cancer linking
      to ultraviolet (UV) radiation using claims data from 1997-2010, obtained from the
      Taiwan National Health Insurance Research Database. The study included 19,701
      patients with pterygium and 78,804 sex- and age-frequency-matched comparison
      subjects. Multivariate Cox regression analyses were performed to assess the
      relationship between pterygium and risk of skin cancer by the end of 2010. The
      incidence rates of malignant melanoma (MM) and nonmelanoma skin cancer (NMSC) in
      two cohorts and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs)
      of the diseases were measured. Results showed that the incidences of MM and NMSC
      were both higher in the pterygium cohort than in the comparison cohort (5.5 vs
      3.2 and 32.3 vs 15.0 per 100,000 person years, respectively). After adjusting for
      age, sex, UV index, occupation, and the other comorbidities, pterygium remained a
      significant predictor of NMSC (hazard ratio [HR], 1.64; 95% confidence interval
      [CI], 1.11-2.42), but not MM (HR, 1.46; 95% CI, 0.59-3.65). These results suggest
      that pterygium patients are associated with an increased risk of NMSC, but not
      significant for MM. 

PMID- 24439049
TI  - Confusion in product packaging.

PMID- 24439047
TI  - Effect of desiccating stress on mouse meibomian gland function.
AB  - PURPOSE: Mice exposed to standardized desiccating environmental stress to induce
      dry eye-like symptoms have been used as a model to study the underlying
      mechanisms of evaporative dry eye. While studies have shown marked inflammatory
      and immune changes, the effect of such stress on meibomian gland function remains
      largely unknown. We sought to evaluate the effects of desiccating stress on
      meibocyte proliferation and meibum quality. METHODS: Ten mice were treated with
      scopolamine and subjected to a drafty low humidity environment (30-35%). Five and
      ten days after treatment, eyelids were harvested and cryosections stained with
      Ki67 antibody to identify cycling cells. Sections were also imaged using
      stimulated Raman scattering (SRS) microscopy to characterize the gland
      compositional changes by detecting the vibrational signatures of methylene
      (lipid) and amide-I (protein). RESULTS: Desiccating stress caused a 3-fold
      increase in basal acinar cell proliferation from 18.3 +/- 11.1% in untreated mice
      to 64.4 +/- 19.9% and 66.6 +/- 13.4% after 5 and 10 days exposure, respectively
      (P < .001). In addition, SRS analysis showed a wider variation in the protein-to
      lipid ratio throughout the gland, suggesting alterations in meibocyte
      differentiation and lipid synthesis. CONCLUSIONS: These data are consistent with
      a model that a desiccating environment may have a direct effect on meibomian
      gland function, leading to a significant increase in basal acinar cell
      proliferation, abnormal meibocyte differentiation, and altered lipid production.

PMID- 24439052
TI  - The relevance of a geriatric assessment for elderly patients with a
      haematological malignancy--a systematic review.
AB  - BACKGROUND: Geriatric assessment is increasingly used to assess the health status
      of older cancer patients. We set out to assemble all available evidence on the
      relevance of a geriatric assessment in the treatment of older patients with
      haematological malignancies. METHODS: A systematic Medline and Embase search for
      studies in which a geriatric assessment was used to detect health issues or to
      address the association between baseline geriatric assessment and outcome.
      RESULTS: 18 publications from 15 studies were included. The median age of
      patients was 73 years (range 58-86). Despite generally good performance status,
      the prevalence of geriatric impairments was high. Geriatric impairments were
      associated with a shorter overall survival in a relevant proportion of studies
      (instrumental activities 55%, nutritional status 67%, cognitive capacities 83%,
      objectively measured physical capacity 100%). Comorbidity, physical capacity and
      nutritional status retained their significance even in multivariate analyses in
      50%, 75%, and 67% of analyses respectively, whereas age and performance status
      lost their predictive value in most studies. One study found an association
      between comorbidity and chemotherapy-related non-haematological toxicity. In
      another study a pronounced association between summarised outcome of geriatric
      assessment and chemotherapy-related toxicity as well as response to treatment was
      described. CONCLUSION: This review demonstrates that a geriatric assessment can
      detect multiple health issues, even in patients with good performance status.
      Impairments in geriatric domains have predictive value for mortality and also
      appear to be associated with toxicity and other outcome measures and should thus
      be integrated in individualised treatment algorithms.

PMID- 24439051
TI  - Poly(ADP-ribose) polymerase inhibitor CEP-8983 synergizes with bendamustine in
      chronic lymphocytic leukemia cells in vitro.
AB  - DNA repair aberrations and associated chromosomal instability is a feature of
      chronic lymphocytic leukemia (CLL). To evaluate if DNA repair insufficiencies are
      related to methylation changes, we examined the methylation of nine promoter
      regions of DNA repair proteins by bisulfide sequencing in 26 CLL primary samples
      and performed quantitative PCR on a subset of samples to examine BRCA1
      expression. We also investigated if changes in cytogenetic or expression level of
      DNA repair proteins led to changes in sensitivity to a novel PARP inhibitor, CEP
      8983, alone and in combination with bendamustine. No changes in promoter
      methylation were identified in BRCA1, BRCA2, FANC-C, FANC-F, FANC-L, ATM, MGMT,
      hMLH1 and H2AX except for two cases of minor BRCA1 hypermethylation. CLL samples
      appeared to have reduced BRCA1 mRNA expression uniformly in comparison to non
      malignant lymphocytes irrespective of promoter hypermethylation. CEP-8983
      displayed single agent cytotoxicity and the combination with bendamustine
      demonstrated synergistic cytotoxicity in the majority of CLL samples. These
      results were consistent across cytogenetic subgroups, including 17p deleted and
      previously treated patients. Our results provide rationale for further
      exploration of the combination of a PARP inhibitor and DNA damaging agents as a
      novel therapeutic strategy in CLL. 

PMID- 24439053
TI  - The prevalence and prognostic value of concomitant eosinophilia in chronic graft
      versus-host disease after allogeneic stem cell transplantation.
AB  - The prognostic significance of eosinophilia after myeloablative allogeneic stem
      cell transplantation (ASCT) remains to be established. Patients, whom developed
      chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142).
      Eosinophil count was analyzed at cGVHD onset. We observed no significant
      association between EO and the grade of cGVHD, thrombocytopenia, nor extensive
      skin involvement. Importantly, we observed no significant association between
      cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup
      analyses revealed a considerable confounding effect of ongoing steroid treatment.
      In conclusion, we advocate that prognostic conclusions regarding cGVHD with
      concomitant eosinophilia after ASCT should be interpreted with caution.

PMID- 24439054
TI  - Therapy-related AML: a slip of the lip can sink a ship.

PMID- 24439055
TI  - Cardiovascular outcomes after elective joint replacement for osteoarthritis.

PMID- 24439056
TI  - Diabesity: palliating, curing or preventing the dysmetabolic diathesis.
AB  - This opinionated evidence-based selective review addresses flawed concepts
      related to "obesity", bariatric surgery and approaches to treatment and
      prevention of a dysmetabolic syndrome of overnutrition and underactivity from the
      perspective of developmental origins of diseases prevalent in mid-life and
      beyond. Innovations focus on methods affecting appetite regulation and energy
      expenditure applicable throughout the life-cycle on the individual level but with
      transgenerational population-wide implications. Readers can expect new knowledge
      and enhanced understanding of a global health problem: "diabesity". 

PMID- 24439057
TI  - Expert consensus on scientific evidence available on the use of botulinum toxin
      in overactive bladder.
AB  - OBJECTIVES: Overactive bladder (OAB) is a pathology impairing patients' quality
      of life and with a high percentage of patients who are refractory to medication.
      In this paper, technical opinion of an "expert panel" is assessed in order to
      gain the most reliable professional consensus on scientific evidence available on
      the criteria of use of Onabotulinumtoxin A (OnabotA) in OAB. MATERIAL AND
      METHODS: according to DELPHI method, 42 panelists answered a survey of 93 items
      divided into four strategic areas including clinical criteria and recommendations
      in order to improve, at different levels, the current approach to patients with
      OAB. The recent advances in the field, areas of controversy and their real
      application possibilities in the different areas of our health care system were
      taken into consideration. RESULTS: Two rounds of the questionnaire were completed
      by all experts. In the first round, a criteria consensus was reached for 64 of 93
      (68.8%) questions analyzed; in the second round the consensus reached was for 83
      items evaluated (89.25%). An agreement among panelist was reached for: 1)
      definition, classification, detection and differential diagnosis; 2) medical
      treatment; 3) surgical treatment; 4) role of OnabotA in the treatment of OAB.
      CONCLUSIONS: the consensus is broadly in line with the latest scientific evidence
      on OAB. The panelists believe that it is necessary to propose a change in the
      current definition of OAB and that it seems necessary to improve the screening
      tools too. Medical treatment of OAB must be tailored to each patient, staged and
      progressive. The use of OnabotA (Botox((r))) could imply therapeutic advantages
      with respect to other treatments, and positions itself as a safe and effective
      alternative to treat drug refractory OAB.

PMID- 24439058
TI  - Maternal long-chain polyunsaturated fatty acid status during early pregnancy and
      children's risk of problem behavior at age 5-6 years.
AB  - OBJECTIVE: To prospectively investigate the association between maternal long
      chain polyunsaturated fatty acid (LCPUFA) status and ratio during pregnancy and
      children's risk of problem behavior at 5 years of age. STUDY DESIGN: Maternal
      LCPUFA status in plasma phospholipids during pregnancy (M = 13.3, SD = 3 weeks)
      was available for 4336 women. Children's behavior was rated by their mother (n =
      2502) and teacher (n = 2061). RESULTS: When using multivariate logistic
      regression analyses, we found that greater concentrations of omega-3 fatty acid
      docosahexaenoic acid (OR 0.75; 95% CI 0.56-0.99; P = .05) decreased children's
      risk for emotional symptoms. Although lower eicosapentaenoic acid and a greater
      omega-6:omega-3 LCPUFA (ie, arachidonic acid/[docosahexaenoic acid +
      eicosapentaenoic acid]) tended to increase the risk for emotional symptoms and
      the risk of hyperactivity/inattention problems for the omega-6:omega-3 LCPUFA,
      the results were nonsignificant (P = .07). No evidence was found for mediation by
      preterm birth and being small for gestational age. The child's sex and infant
      feeding pattern did not modify the associations. CONCLUSION: Our results suggest
      long-term developmental programming influences of maternal LCPUFA status during
      pregnancy and stress the importance of an adequate and balanced supply of fatty
      acids in pregnant women for optimal fetal brain development and subsequent long
      term behavioral outcomes.

PMID- 24439061
TI  - The role of microRNA profiling in prognosticating progression in Ta and T1
      urinary bladder cancer.
AB  - OBJECTIVE: To analyze microRNA profile in Ta and T1 urinary bladder cancers in
      combination and separately and to relate this to the risk of later developing
      higher-stage disease. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded
      samples of 44 Ta and 42 T1 bladder cancers representing cases with and without
      stage progression during follow-up were collected and microRNA expression levels
      were measured by microarray analysis. RESULTS: In a comparison between the
      progressors and controls, in the Ta/T1 group, miR-10a-5p and miR-31-5p were
      differentially expressed. miR-10a-5p was also correlated to time to progression
      (P = 0.00012). In the subgroup analysis, 3 microRNAs, miR-10a-5p, miR-31-5p, and
      miR-130a-3p, were differentially expressed among Ta tumors and had a fold change
      of more than 1.5 (P<0.038). The comparison concerning microRNA expression between
      the progressors and controls in category T1 cancers revealed no significant
      differences. CONCLUSIONS: Profiling revealed that certain microRNAs predicted the
      risk of developing higher-stage disease among patients with Ta cancers. Lower miR
      10a-5p expression in Ta progressing tumors indicates that this microRNA could be
      important for later malignant potential among this group of patients.

PMID- 24439063
TI  - Effects of step length on patellofemoral joint stress in female runners with and
      without patellofemoral pain.
AB  - BACKGROUND: Patellofemoral pain is common among runners and is frequently
      attributed to increased patellofemoral joint stress. The purpose of our study was
      to examine the effects of changing step length during running on patellofemoral
      joint stress per step and stress per mile in females with and without
      patellofemoral pain. METHODS: Ten female runners with patellofemoral pain and 13
      healthy female runners performed running trials at 3.7m/s in three conditions:
      preferred step length, at least +10% step length, and at least -10% step length.
      Knee flexion angles and internal knee extension moments served as inputs for a
      biomechanical model to estimate patellofemoral joint stress per step. We also
      estimated total patellofemoral joint stress per mile based on the number of steps
      necessary to run a mile during each condition. FINDINGS: Patellofemoral joint
      stress per step increased 31% in the long step length condition (P<.001) and
      decreased 22.2% in the short step length condition (P<.001). Despite the inverse
      relationship between step length and number of steps required to run a mile,
      patellofemoral joint stress per mile increased 14% in the long step length
      condition (P<.001) and decreased 7.5% in the short step length condition
      (P<.001). INTERPRETATION: These results suggest a direct relationship between
      step length and patellofemoral joint loads. Total stress per mile experienced at
      the patellofemoral joint decreased with a short step length despite the greater
      number of steps necessary to cover this distance. These findings may have
      relevance with respect to both prevention and treatment of patellofemoral joint
      pain.

PMID- 24439066
TI  - Risk factors for acute kidney injury in patients treated with polymyxin B or
      colistin methanesulfonate sodium.
AB  - Polymyxin B (PMB) and colistin, administered as the prodrug colistin
      methanesulfonate sodium (CMS), are increasingly used to treat carbapenem
      resistant Gram-negative bacteria. Nephrotoxicity is the major dose-limiting
      adverse effect of both polymyxins. A retrospective cohort study of 132 patients
      was conducted to evaluate risk factors for acute kidney injury (AKI), classified
      according to Acute Kidney Injury Network criteria, in patients treated with >=48h
      of intravenous PMB or CMS, with particular focus on potential differences between
      each polymyxin. The overall incidence of AKI was 25.8% (34/132) [20.8% (20/96)
      and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P=0.06]. In
      the Cox regression model, doses >=2million International Units (MIU) of PMB or
      >9MIU of CMS were the only variable independently associated with AKI [adjusted
      hazard ratio (aHR)=2.11, 95% confidence interval (CI) 1.01-4.41; P=0.04].
      Vancomycin co-administration was strongly associated with AKI, although this was
      not statistically significant (aHR=2.22, 95% CI 0.98-5.04; P=0.058). There was no
      statistically significant difference in the incidence of AKI between patients
      treated with PMB or CMS in the multivariate model (aHR=1.74, 95% CI 0.82-3.69;
      P=0.15). High dose was the main risk factor for AKI regardless of the polymyxin
      administered. Vancomycin co-administration likely increases the risk of AKI.
      Although there was a higher overall incidence of AKI in patients treated with CMS
      compared with PMB, CMS was not significantly associated with this outcome after
      adjusting for the above variables. 

PMID- 24439067
TI  - Association between N-terminal pro-brain natriuretic peptide and quality of life
      in adult patients with congenital heart disease.
AB  - AIMS: Advances in medical treatment have resulted in increased life expectancy in
      congenital heart disease. Consequently, the focus of management has shifted from
      reducing mortality to reducing long-term morbidity with the goal of improving
      quality of life. A predictor of quality of life might be N-terminal pro-brain
      natriuretic peptide, a well-established marker for heart failure. We aimed to
      determine the association between N-terminal pro-brain natriuretic peptide and
      quality of life in patients with congenital heart disease. METHODS: We collected
      blood samples from consecutive patients who were initially operated between 1968
      and 1980 (47.8% women; mean age 40.2+/-5.4 years). The 36-item Short-Form Health
      Survey was completed to assess subjective health status as a measure of quality
      of life. Analysis was performed for the entire group and for subgroups defined as
      simple versus complex congenital heart diseases. Median N-terminal pro-brain
      natriuretic peptide level was 15.2 pmol/L (overall range 1.3-299.3 pmol/L). N
      terminal pro-brain natriuretic peptide levels were associated with the subdomain
      physical functioning (beta=-0.074, p=0.031). This association remained
      significant after adjustment for age and sex (beta=-0.071, p=0.038) and after
      adjustment for age, sex, body mass index, left ventricular function, and renal
      function (beta=-0.069, p=0.048). In complex congenital heart disease, the
      association between N-terminal pro-brain natriuretic peptide and physical
      functioning remained significant in multivariable analysis (beta=-0.076,
      p=0.046). No associations were found in the simple congenital heart disease group
      or on the other health status subdomains. CONCLUSION: In adults operated for
      congenital heart disease, N-terminal pro-brain natriuretic peptide is associated
      with the subdomain physical, primarily in the complex subgroup.

PMID- 24439068
TI  - There was less self-critique among basic than in clinical science articles in
      three rheumatology journals.
AB  - OBJECTIVES: There is concern that self-critique with authors acknowledging
      limitations of their work is not given due importance in scientific articles. We
      had the impression that this was more true for articles in basic compared with
      clinical science. We thus surveyed for the presence of self-critique in the
      discussion sections of the original articles in three rheumatology journals with
      attention to differences between the basic and the clinical science articles.
      STUDY DESIGN AND SETTING: The discussion sections of the original articles in
      January, May, and September 2012 issues of Annals of the Rheumatic Diseases,
      Arthritis and Rheumatism, and Rheumatology (Oxford) were surveyed (n = 223) after
      classifying each article as mainly related to clinical or basic science. The
      discussion sections were electronically scanned by two observers for the presence
      of the root word "limit" or its derivatives who also read each discussion section
      for the presence of any limitations otherwise voiced. RESULTS: A limitation
      discussion in any form was present in only 19 (20.2%) or 29 (30.1%) of 94 basic
      science vs. 95 (73.6%) or 107 (82.3%) of 129 clinical science articles (P <
      0.0001 for either observer). CONCLUSION: Self-critique, especially lacking in
      basic science articles, should be given due attention.

PMID- 24439069
TI  - Oncology trial abstracts showed suboptimal improvement in reporting: a
      comparative before-and-after evaluation using CONSORT for Abstract guidelines.
AB  - OBJECTIVES: The aims of this study were to evaluate the quality of randomized
      controlled trial (RCT) abstracts published in the field of oncology and identify
      characteristics associated with better reporting quality. STUDY DESIGN AND
      SETTING: All phase III trials published during 2005-2007 [before Consolidated
      Standards of Reporting Trials (CONSORT)] and 2010-2012 (after CONSORT) were
      searched electronically in MEDLINE/PubMed and retrieved for review using an 18
      point overall quality score (OQS) for reporting based on the CONSORT for Abstract
      guidelines. Descriptive statistics followed by multivariate linear regression
      were used to identify features associated with improved reporting quality.
      RESULTS: The mean OQS was 8.2 (range: 5-13; 95% confidence interval (CI): 8.0,
      8.3) and 9.9 (range: 5-18; 95% CI: 9.7, 10.2) in the pre- and post-CONSORT
      periods, respectively. The method for random sequence generation, allocation
      concealment, blinding details, and funding sources were missing in pre-CONSORT
      abstracts and insufficiently reported (<20%) in post-CONSORT abstracts. A high
      impact factor (P < 0.001) and the journal of publication (P < 0.001) were
      independent factors that were significantly associated with higher reporting
      quality on multivariate analysis. CONCLUSION: The reporting quality of RCT
      abstracts in oncology showed suboptimal improvement over time. Thus, stricter
      adherence to the CONSORT for Abstract guidelines is needed to improve the
      reporting quality of RCT abstracts published in oncology.

PMID- 24439070
TI  - A myriad of methods: calculated sample size for two proportions was dependent on
      the choice of sample size formula and software.
AB  - OBJECTIVES: Several methods exist to calculate sample size for the difference of
      proportions (risk difference). Researchers are often unaware that there are
      different formulae, different underlying assumptions, and what the impact of
      choice of formula is on the calculated sample size. The aim of this study was to
      discuss and compare different sample size formulae for the risk difference. STUDY
      DESIGN AND SETTING: Four sample size formulae were used to calculate sample size
      for nine scenarios. Software documentation for SAS, Stata, G*Power, PASS,
      StatXact, and several R libraries were searched for default assumptions. Each
      package was used to calculate sample size for two scenarios. RESULTS: We
      demonstrate that for a set of parameters, sample size can vary as much as 60%
      depending on the formula used. Varying software and assumptions yielded
      discrepancies of 78% and 7% between the smallest and largest calculated sizes,
      respectively. Discrepancies were most pronounced when powering for large risk
      differences. The default assumptions varied considerably between software
      packages, and defaults were not clearly documented. CONCLUSION: Researchers
      should be aware of the assumptions in power calculations made by different
      statistical software packages. Assumptions should be explicitly stated in grant
      proposals and manuscripts and should match proposed analyses.

PMID- 24439071
TI  - Influence of repeated insertion-removal cycles on the force and magnetic flux
      leakage of magnetic attachments: an in vitro study.
AB  - STATEMENT OF PROBLEM: Magnetic attachments are widely used in overdentures and
      maxillofacial prostheses. Because the patient will routinely have to insert and
      remove a removable prosthesis, the retentive force and magnetic flux leakage of
      the magnetic attachments after repeated insertion and removal must be evaluated
      to assess their clinical performance. PURPOSE: The purpose of this in vitro study
      was to investigate the retentive force and flux leakage of magnetic attachments
      after repeated insertion and removal. MATERIAL AND METHODS: Magfit EX600W magnet
      keeper combinations (n=5) were used in this study. After 5000, 10,000, and 20,000
      insertion-removal cycles, the retentive force of the magnetic attachments was
      measured 5 times at a crosshead speed of 5 mm/min with a universal testing
      machine. Magnetic flux leakage at 3 positions (P1, the upper surface of the
      magnet; P2, the lower surface of the keeper; and P3, the lateral side of the
      magnetic attachment set) was evaluated with a gaussmeter. Data were statistically
      analyzed by 1-way ANOVA (alpha=.05). The morphology of the abraded surfaces for
      both the magnet and the keeper was observed with an optical microscope (5*).
      RESULTS: The mean retentive force decreased significantly after 5000, 10,000, and
      20,000 insertion-removal movements (P<.05). Significant differences of flux
      leakage were also observed at P1 after 5000 cycles and 10,000 cycles, at P2 after
      5000 cycles, and at P3 after 5000, 10,000, and 20,000 insertion-removal cycles (P
      < .05). However, no significant differences in flux leakage were evident after
      20,000 cycles at P1 and 10,000 cycles and 20,000 cycles at P2. CONCLUSIONS:
      Repeated insertion and removal influenced the retentive force and magnetic flux
      leakage of the magnetic attachments. Retentive force decreased significantly
      after repeated insertion-removal cycles, whereas the variation of magnetic flux
      leakage depended on refitting cycles and positions of the magnetic attachments.

PMID- 24439072
TI  - Long-cherished dreams for epileptologists and clinical neurophysiologists:
      automatic seizure detection in long-term scalp EEG.

PMID- 24439074
TI  - Late onset of vaccine-associated measles in an adult with severe clinical
      symptoms: a case report.

PMID- 24439075
TI  - Bacteriuria in individuals who become delirious.

PMID- 24439076
TI  - Intralymphatic immunotherapy: time interval between injections is essential.

PMID- 24439077
TI  - Electron microscopy elucidates eosinophil degranulation patterns in patients with
      eosinophilic esophagitis.
AB  - BACKGROUND: In patients with eosinophilic esophagitis (EoE), eosinophils
      accumulate and release granule proteins onto esophageal epithelium. However,
      little is understood about the mechanism of eosinophil degranulation. OBJECTIVE:
      To determine and quantify eosinophil degranulation patterns, we studied
      esophageal biopsy specimens from both the proximal and distal esophagi of 9
      randomly selected patients with EoE. METHODS: The specimens were fixed in
      glutaraldehyde, embedded, sectioned, and imaged by means of transmission electron
      microscopy. Eosinophils and their granules were identified by their distinctive
      morphology, and all eosinophils and granules were imaged. A total of 1672 images
      from 18 esophageal specimens were evaluated and graded. Eosinophils were
      categorized based on membrane integrity and by cytoplasmic vesiculation as
      evidence of piecemeal degranulation. Granules were categorized based on reversal
      of staining (eosinophil granule core lightening) and localization within and
      outside the cells. RESULTS: The results revealed that greater than 98% of
      eosinophils infiltrating the esophagus in patients with EoE demonstrate
      morphologic abnormalities ranging from granule changes with reversal of staining
      to marked cytoplasmic vesiculation to loss of cellular membrane integrity with
      cytolytic disruption and release of intact membrane-bound granules into the
      tissues. Approximately 81% of eosinophils showed membrane disruption.
      Extracellular granules were abundant in at least 70% of the images, and
      approximately 50% of these granules showed reversal of staining. On the basis of
      the prominence of tubulovesicular development, piecemeal degranulation appears
      closely related to the other morphologic changes seen in patients with EoE.
      CONCLUSION: These findings reveal that eosinophils in esophageal biopsy specimens
      from patients with EoE are abnormal, with greater than 80% showing cytolysis, and
      therefore that evaluation by means of light microscopy after hematoxylin and
      eosin staining might not accurately reflect eosinophil involvement.

PMID- 24439078
TI  - Reply: To PMID 24035151.

PMID- 24439079
TI  - Reply: To PMID 23987798.

PMID- 24439080
TI  - Pulmonary alveolar proteinosis in adenosine deaminase-deficient mice.

PMID- 24439081
TI  - Idiopathic, asymptomatic, and durable blood hypereosinophilia-still many
      unknowns.

PMID- 24439082
TI  - Reply: To PMID 23910691.

PMID- 24439083
TI  - Serum levels of bone cytokines in indolent systemic mastocytosis associated with
      osteopenia or osteoporosis.

PMID- 24439084
TI  - [Which definition and taxonomy of incident to use for a French reporting system
      in primary care settings?].
AB  - BACKGROUND: There is no widely accepted definition of incident for primary care
      doctors in France and no taxonomic classification system for epidemiological use.
      In preparation for a future epidemiological study on primary care incidents in
      France (the ESPRIT study), this work was designed to identify the definitions and
      taxonomic classifications used internationally along with the usual methods and
      results in terms of frequency in the literature. The goal was to determine a
      French definition and taxonomy. DESIGN: Systematic review of the literature and
      consensus methods. METHOD: An exhaustive search of epidemiological surveys was
      performed. A structured grid was used. After having identified the definitions
      used in the literature, a definition was chosen using the focus groups method.
      Taxonomies identified in the literature were classified by relationship,
      architecture, code number, and number of studies published. Subsequently, a
      consensus among experts, who independently tested these taxonomies on six
      incidents, was reached for choosing the most appropriate for epidemiological data
      collection (little information on a large number of cases). RESULTS: Twenty-four
      papers reporting 17 studies were selected among 139 articles. Five definitions
      and eight taxonomies were found. The chosen definition of incident was based on
      the WHO definition "A patient safety incident is an event or circumstance that
      could have resulted, or did result, in harm to a patient, and whose wish it is
      not repeated again". The test of incidents resulted in the choice of the TAPS
      version of the International Taxonomy of Medical Error in Primary Care for a
      reproducible and internationally recognized codification and the tempos method
      for its current use in French general practice. DISCUSSION: The definitions,
      taxonomies, data collection characteristics and frequency of incidents results in
      the international literature on incidents in primary care are key components for
      the preparation of an epidemiological survey on incidents in primary care.

PMID- 24439088
TI  - The health consequences of our fiscal crisis.

PMID- 24439089
TI  - We need a global revolution in consciousness that helps us remember our oneness;
      helps us remember that everything is sacred.

PMID- 24439091
TI  - The heart of the matter--the deeper meaning of healing.

PMID- 24439092
TI  - Intention-based therapy for autism spectrum disorder: promising results of a wait
      list control study in children.
AB  - BACKGROUND: Autism is a complex neurodevelopmental disability that usually
      manifests during the first three years of life and typically lasts throughout a
      person's lifetime. The purpose of this study is to investigate the efficacy of
      NeuroModulation Technique (NMT), a form of intention-based therapy, in improving
      functioning in children diagnosed with autism. METHODS: A total of 18 children
      who met the study criteria were selected to participate. All children completed
      baseline measures. The children in the experimental group (n = 9) received two
      sessions a week of NMT for six weeks. Then, children in the wait-list control
      group (n = 9) received two sessions a week of NMT for six weeks. Primary efficacy
      outcome measures included the Pervasive Developmental Disorder Behavioral
      Inventory Autism Composite Index, the Aberrant Behavior Checklist-Community Total
      Score, and the Autism Treatment Evaluation Checklist Total Score. Our hypotheses
      were that children in both groups would show significant improvement over their
      respective baseline scores following NMT treatment, which would reflect an
      improvement in adaptive behaviors as well as a decrease in maladaptive behaviors.
      RESULTS: Statistical analysis indicates a significant improvement in both the
      experimental and wait-list control group on all primary outcome measures
      following NMT treatment. The wait-list control group demonstrated no significant
      improvement on test measures over baseline scores during the wait period. No
      adverse reactions were reported. CONCLUSIONS: These findings suggest that NMT is
      a promising intervention for autism that has the potential to produce a
      significant reduction in maladaptive behaviors and a significant increase in
      adaptive behaviors within a relatively short period of time.

PMID- 24439093
TI  - CAM and energy psychology techniques remediate PTSD symptoms in veterans and
      spouses.
AB  - Male veterans and their spouses (N = 218) attending one of six-week-long retreats
      were assessed for posttraumatic stress disorder (PTSD) symptoms pre- and
      postintervention. Participants were evaluated using the PTSD checklist (PCL), on
      which, a score of >49 indicates clinical symptom levels. The mean pretest score
      was 61.1 (SD +/- 12.5) for veterans and 42.6 (SD +/- 16.5) for spouses; 83% of
      veterans and 29% of spouses met clinical criteria. The multimodal intervention
      used Emotional Freedom Techniques and other energy psychology (EP) methods to
      address PTSD symptoms and a variety of complementary and alternative medicine
      (CAM) modalities for stress reduction and resource building. Interventions were
      delivered in group format as well as individual counseling sessions. Data were
      analyzed for each retreat, as well as for the six retreats as a whole. Mean post
      test PCL scores decreased to 41.8 (SE +/- 1.2; p < .001) for veterans, with 28%
      still clinical. Spouses demonstrated substantial symptom reductions (M = 28.7, SE
      +/- 1.0; p < .001), with 4% still clinical. A follow-up assessment (n = 63) found
      PTSD symptom levels dropping even further for spouses (p < .003), whereas gains
      were maintained for veterans. The significant reduction in PTSD symptoms is
      consistent with other published reports of EP treatment, though counter to the
      usual long-term course of the condition. The results indicate that a multimodal
      CAM intervention incorporating EP may offer benefits to family members as well as
      veterans suffering from PTSD symptoms. Recommendations are made for further
      research to answer the questions posed by this study. 

PMID- 24439094
TI  - Older adults' perspectives on naturopathic medicine's impact on healthy aging.
AB  - CONTEXT: High rates of complementary and alternative medicine (CAM) utilization
      among older adults are of interest because studies suggest relationships among
      CAM, self-care, and healthy lifestyle. These potential relationships are of
      particular interest because of the contribution of self-care in maintaining
      physical, emotional, and spiritual health as key strategies to successful aging.
      Naturopathic medicine (NM) is a type of primary care CAM used by older adults,
      yet little is known about older adults' use of NM or its role in healthy aging.
      OBJECTIVES: We sought to examine perceptions about, and utilization of, NM and
      the experience of addressing health and wellness as part of the aging process.
      DESIGN: Phenomenology-based qualitative inquiry. SETTING: A total of 13 community
      based clinics affiliated with a naturopathic medical school. PARTICIPANTS: A
      total of 47 adults aged 58-100 years. METHODS: Qualitative analysis of semi
      structured focus groups with quantitative analysis of clinical administrative
      data. RESULTS: Over 2543 older adults used NM services affiliated with a natural
      academic clinic in Seattle in 2011 for diagnoses consistent with primary care:
      fatigue, anxiety, diabetes, diarrhea, and depression, in rank order. Participants
      reported they sought NM because it offered a different system of care aligned
      with their values. Themes included (1) feeling heard, (2) a focus on health
      education including prevention and self-care, and (3) feeling supported. Themes
      further distilled into optimal descriptive characteristics of patient-centered
      providers that may best support older adults' healthy aging. A final theme
      described barriers to further utilization.

PMID- 24439095
TI  - Acupuncture-based modalities: novel alternative approaches in the treatment of
      gastrointestinal dysmotility in patients with systemic sclerosis.
AB  - BACKGROUND: The gastrointestinal (GI) dysmotility of systemic sclerosis (SSc,
      scleroderma) patients requires careful evaluation and intervention. The lack of
      effective prokinetic drugs motivate researchers to search for alternative
      treatments. OBJECTIVES: We present an overview of the pathophysiology of SSc GI
      dysmotility and the advances in its management, with particular focus on
      acupuncture-related modalities and innovative therapies. DATA SOURCES: Original
      research articles were identified based on the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guideline methodology. We have
      searched the MEDLINE database using Medical Subject Heading (MeSH) for all
      English and non-English articles with an English abstract from 2005 to October
      2012. RESULTS: Only four original articles of various study designs were found
      studying Complementary and Alternative Medicine (CAM) therapies for SSc patients.
      Despite the small patient study numbers, CAM treatments, acupressure, and
      transcutaneous electroacupuncture, showed self-reported and physiologic evidence
      of improvement of GI functioning and/or symptoms in SSc patients. CONCLUSIONS:
      CAM therapies include experimental modalities with the potential to offer relief
      of symptoms from GI dysmotility. Larger studies are needed to investigate their
      optimal use in patient subsets to tailor therapies to patient needs.

PMID- 24439096
TI  - Low-level electric current and cancer--a promising, but languishing non-toxic
      cancer therapy.

PMID- 24439097
TI  - Pain after hip arthroplasty managed by Brennan Healing Science.
AB  - A case is presented illustrating the potential effect of Brennan Healing Science
      on pain following hip arthroplasty for avascular necrosis. A 54-year-old woman
      experienced anterior groin pain, numbness at the bottom of her foot, and
      occasional grinding at her hip 22 years after right total hip arthroplasty
      secondary to avascular necrosis. X-ray films showed signs of osteolysis behind
      the acetabular cup and asymmetric decreased polyethylene thickness of the
      acetabular prosthetic. Her orthopedic surgeon advised the patient to follow up
      every 6-9 months to avoid catastrophic failure of the implant, with plans for
      surgical revision to be scheduled at the next appointment. The patient sought
      alternative treatment to avoid an invasive procedure. On presentation, the
      patient had difficulty walking up the stairs into the treatment room due to pain
      which she rated a 9/10. She found it painful to rotate, flex, extend her hip, or
      to sit. Hands-on healing techniques based on the Brennan Healing Science method
      were initiated, starting at the feet, balancing the energy, and working the way
      up the joints. Once the work at the hip was completed, the hands-on techniques
      continued up the centerline of the body and the healing was brought to a close.
      On completion of a 60-minute healing, the patient was able to stand freely and
      rated her pain as a 4/10. Flexion, extension, and rotation at the hip were no
      longer distressing. She was able to walk up and down stairs without distress and
      denied instability, bursitis, or trochanteric or iliopsoas pain or swelling.
      Repeat X-rays showed decrease in bone spurs and no hardware problem, and her
      orthopedic surgeon recommended follow-up after 2 years. It is suggested that
      Brennan Healing Science techniques could play an effective and cost-efficient
      role in the treatment of pain following hip arthroplasty. 

PMID- 24439098
TI  - Osteopathy and low back pain, acupuncture and in vitro fertilization, Tai Chi and
      osteoarthritis, Andrographis paniculata and ulcerative colitis, and acupressure
      and vertigo.

PMID- 24439099
TI  - The encouragement of light: reflecting on Leaps 2013.

PMID- 24439101
TI  - [Prevention of complications in the air transport of the critically ill pediatric
      patient between hospitals].
AB  - OBJECTIVES: To analyze the rate of complications recorded during patient
      transport after applying a stabilization protocol in the sending hospital,
      defined by a paediatric critical patients air transport unit. MATERIAL AND
      METHODS: We retrospectively analyzed the transfers made by the air unit of our
      hospital over a 5 years period. Patients with respiratory failure, hemodynamic
      compromise, or neurological involvement were identified. The stabilization
      protocol prior to transport is described. Operations performed during
      stabilization period, as well as during the transfer are quantified.
      Complications during transport are recorded and classified into major and minor
      ones. RESULTS: A total of 388 patients were transferred, of which 207 had
      respiratory failure, 124 neurological disorders, and 102 with hemodynamic
      instability. During the stabilization period, 295 patients required oxygen and
      161 mechanical ventilation. A total of 14 pleural drains, 397 peripheral lines
      and 97 central lines were placed. Vasoactive drugs were administered on 92
      occasions and anticonvulsants in 41. We have performed 24 cardiopulmonary
      resuscitation, and 2 patients died before the move, and one required surgery.
      Twenty major complications have been recorded during transfer (6 neurological, 13
      hemodynamic, and 1 respiratory), and 69 minor complications (14 neurological, 29
      hemodynamic and 26 respiratory). One patient died. CONCLUSION: Compliance with
      defined stabilization standards led to a high rate of interventions during the
      preparation phase. On the other hand, a small number of complications occurred
      during transport: only 5.1% of the patients showed any serious complication. This
      low rate of complications is attributable to a correct stabilization carried out
      prior to transfer, and based on the standards adopted by the team.

PMID- 24439102
TI  - [Antidote use in a pediatric emergency department].
AB  - INTRODUCTION: Poisoning is an infrequent cause of consultation in a pediatric
      emergency department (PED), but it can be potentially serious. Pediatricians
      should know how to use the available antidotes properly. OBJECTIVES: To analyze
      the use of antidotes in a PED and to assess the suitability of their indications.
      MATERIALS AND METHODS: A retrospective review of antidote use in a PED between
      January 2008 and June 2012. Inclusion criteria were age younger than 18 years and
      consultation for suspicious poisoning by a substance that could be treated with
      an antidote. The adequacy of antidote indication was based on the recommendations
      of the Spanish Society of Pediatric Emergencies (SSPE). RESULTS: A total of 1728
      consultations for suspicious poisoning (0.4% of the total visits in the PED) were
      recorded. In 353 cases (20.4%) the involved poison could be treated with an
      antidote. Sixty-seven patients received an antidote (3.9% of consultations for
      suspicious poisoning), and a total of 69 administrations of an antidote were
      made: 100% oxygen (46), N-acetylcysteine (10), flumazenil (4), naloxone (3),
      deferoxamine (2), vitamin K (2), bicarbonate (1), and carnitine (1). In 3 cases
      there was no indication for administration: flumazenil without respiratory
      depression, and vitamin K following coumarin exposure. As side effects, agitation
      was noted after the use of flumazenil, and a decrease in the prothrombin time
      during infusion of N-acetylcysteine. CONCLUSIONS: The administration of antidotes
      in this PED is uncommon and, mainly, in accordance with the SSPE recommendations,
      and without serious side effects. The use of flumazenil needs to be limited to
      the cases with a clear indication and without any contraindication.

PMID- 24439103
TI  - [Usefulness of procalcitonin for prescribing of antibiotics and suspicion of
      bacteremia in the emergency department. Author's reply].

PMID- 24439104
TI  - A simple method of creating a vent hole in a stone cast by using a metal sprue
      cone.

PMID- 24439105
TI  - Fabrication of an immediate surgical obturator for a patient with resection of
      the maxillary antrum and bony orbital floor.
AB  - An immediate surgical obturator is necessary for maxillectomy procedures to
      minimize functional disabilities in speech, swallowing, and egress of food and
      liquid into the surgical defect. Sometimes the extent of the tumor may be such
      that it may even require the removal of the maxillary sinus along with resection
      of the orbital floor. The resected orbital floor can be surgically reconstructed
      with autogenous soft and/or hard tissues or with alloplastic materials. This
      clinical report highlights one such situation where the surgical resection of the
      maxilla and the orbital floor were rehabilitated with an immediate surgical
      obturator extending to the orbital floor to support the visual apparatus.

PMID- 24439106
TI  - Effect of porcelain and enamel thickness on porcelain veneer failure loads in
      vitro.
AB  - STATEMENT OF PROBLEM: Bonded porcelain veneers are widely used esthetic
      restorations. Although high success and survival rates have been reported,
      failures occur. Fracture is the most common failure mode. Fractures range from
      incomplete cracks to the catastrophic. Minimally invasive or thin partial veneers
      have gained popularity. PURPOSE: The aim of this study was to measure the
      influences of porcelain veneer thickness and enamel substrate thickness on the
      loads needed to cause the initial fracture and catastrophic failure of porcelain
      veneers. MATERIAL AND METHODS: Model discoid porcelain veneer specimens of
      varying thickness were bonded to the flattened facial surfaces of incisors,
      artificially aged, and loaded to failure with a small sphere. Individual fracture
      events were identified and analyzed statistically and fractographically. RESULTS:
      Fracture events included initial Hertzian cracks, intermediate radial cracks, and
      catastrophic gross failure. Increased porcelain, enamel, and their combined
      thickness had like effects in substantially raising resistance to catastrophic
      failure but also slightly decreased resistance to initial Hertzian cracking.
      Fractographic and numerical data demonstrated that porcelain and tooth enamel
      behaved in a remarkably similar manner. As porcelain thickness, enamel thickness,
      and their combined thickness increased, the loads needed to produce initial
      fracture and catastrophic failure rose substantially. Porcelain veneers withstood
      considerable damage before catastrophic failure. CONCLUSIONS: Increased enamel
      thickness, increased porcelain thickness, and increased combined enamel and
      porcelain thickness all profoundly raised the failure loads necessary to cause
      catastrophic failure. Enamel and feldspathic porcelain behaved in a like manner.
      Surface contact damage occurred initially. Final catastrophic failure followed
      flexural radial cracking. Bonded porcelain veneers were highly damage tolerant.

PMID- 24439107
TI  - Neurological imaging of brain damages after radiotherapy and/or chimiotherapy.
AB  - Radiotherapy and chemotherapy may induce neurological toxicities with different
      appearances on CT and MRI scans. While optimized radiotherapy techniques have
      reduced some complications, new unwanted effects have occurred on account of
      therapeutic protocols involving the simultaneous use of radiotherapy and
      chemotherapy. Advances in radio-surgery, innovative anti-angiogenic therapies, as
      well as prolonged patient survival have led to the emergence of new deleterious
      side effects. In this report, we describe the early, semi-delayed, and late
      encephalic complications, while specifying how to identify the morphological
      lesions depending on the therapeutic protocol. 

PMID- 24439108
TI  - [Acute abdomen secondary to perforated jejunal diverticulitis].

PMID- 24439109
TI  - Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis
      in humans.
AB  - Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of
      kidney development defects including renal agenesis, hypoplasia, and (cystic)
      dysplasia. Heterozygous mutations of several genes have been identified as
      genetic causes of RHD with various severity. However, these genes and mutations
      are not associated with bilateral renal agenesis, except for RET mutations, which
      could be involved in a few cases. The pathophysiological mechanisms leading to
      total absence of kidney development thus remain largely elusive. By using a whole
      exome sequencing approach in families with several fetuses with bilateral renal
      agenesis, we identified recessive mutations in the integrin alpha8-encoding gene
      ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in
      absence of kidney development. We provide evidence of a damaging effect of the
      human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a
      genetic cause of bilateral renal agenesis and that, at least in some cases,
      bilateral renal agenesis is an autosomal-recessive disease.

PMID- 24439110
TI  - Mutations in PGAP3 impair GPI-anchor maturation, causing a subtype of
      hyperphosphatasia with mental retardation.
AB  - Glycosylphophatidylinositol (GPI)-anchored proteins play important roles in many
      biological processes, and mutations affecting proteins involved in the synthesis
      of the GPI anchor are reported to cause a wide spectrum of intellectual
      disabilities (IDs) with characteristic additional phenotypic features. Here, we
      describe a total of five individuals (from three unrelated families) in whom we
      identified mutations in PGAP3, encoding a protein that is involved in GPI-anchor
      maturation. Three siblings in a consanguineous Pakistani family presented with
      profound developmental delay, severe ID, no speech, psychomotor delay, and
      postnatal microcephaly. A combination of autozygosity mapping and exome
      sequencing identified a 13.8 Mb region harboring a homozygous c.275G>A
      (p.Gly92Asp) variant in PGAP3 region 17q11.2-q21.32. Subsequent testing showed
      elevated serum alkaline phosphatase (ALP), a GPI-anchored enzyme, in all three
      affected children. In two unrelated individuals in a cohort with developmental
      delay, ID, and elevated ALP, we identified compound-heterozygous variants
      c.439dupC (p.Leu147Profs(*)16) and c.914A>G (p.Asp305Gly) and homozygous variant
      c.314C>G (p.Pro105Arg). The 1 bp duplication causes a frameshift and nonsense
      mediated decay. Further evidence supporting pathogenicity of the missense
      mutations c.275G>A, c.314C>G, and c.914A>G was provided by the absence of the
      variants from ethnically matched controls, phylogenetic conservation, and
      functional studies on Chinese hamster ovary cell lines. Taken together with
      recent data on PGAP2, these results confirm the importance of the later GPI
      anchor remodelling steps for normal neuronal development. Impairment of PGAP3
      causes a subtype of hyperphosphatasia with ID, a congenital disorder of
      glycosylation that is also referred to as Mabry syndrome.

PMID- 24439112
TI  - A yet unreported der(11)t(6;11)(p21;q21) included in a complex karyotype of a
      refractory anemia with ring sideroblasts and poor prognosis.

PMID- 24439113
TI  - Distinctive spontaneous regional neural activity in patients with somatoform pain
      disorder: a preliminary resting-state fMRI study.
AB  - This resting-state functional magnetic resonance imaging study found that nine
      patients with somatoform pain disorder exhibited atypical precentral gyrus
      activation compared with 20 healthy controls. The role of the precentral gyrus in
      pain-related processing is discussed. 

PMID- 24439111
TI  - A common functional regulatory variant at a type 2 diabetes locus upregulates
      ARAP1 expression in the pancreatic beta cell.
AB  - Genome-wide association studies (GWASs) have identified more than 70 loci
      associated with type 2 diabetes (T2D), but for most, the underlying causal
      variants, associated genes, and functional mechanisms remain unknown. At a T2D-
      and fasting-proinsulin-associated locus on 11q13.4, we have identified a
      functional regulatory DNA variant, a candidate target gene, and a plausible
      underlying molecular mechanism. Fine mapping, conditional analyses, and exome
      array genotyping in 8,635 individuals from the Metabolic Syndrome in Men study
      confirmed a single major association signal between fasting proinsulin and
      noncoding variants (p = 7.4 * 10(-50)). Measurement of allele-specific mRNA
      levels in human pancreatic islet samples heterozygous for rs11603334 showed that
      the T2D-risk and proinsulin-decreasing allele (C) is associated with increased
      ARAP1 expression (p < 0.02). We evaluated four candidate functional SNPs for
      allelic effects on transcriptional activity by performing reporter assays in
      rodent pancreatic beta cell lines. The C allele of rs11603334, located near one
      of the ARAP1 promoters, exhibited 2-fold higher transcriptional activity than did
      the T allele (p < 0.0001); three other candidate SNPs showed no allelic
      differences. Electrophoretic mobility shift assays demonstrated decreased binding
      of pancreatic beta cell transcriptional regulators PAX6 and PAX4 to the
      rs11603334 C allele. Collectively, these data suggest that the T2D-risk allele of
      rs11603334 could abrogate binding of a complex containing PAX6 and PAX4 and thus
      lead to increased promoter activity and ARAP1 expression in human pancreatic
      islets. This work suggests that increased ARAP1 expression might contribute to
      T2D susceptibility at this GWAS locus.

PMID- 24439115
TI  - Three-year-olds obey the sample size principle of induction: the influence of
      evidence presentation and sample size disparity on young children's
      generalizations.
AB  - Three experiments with 81 3-year-olds (M=3.62years) examined the conditions that
      enable young children to use the sample size principle (SSP) of induction-the
      inductive rule that facilitates generalizations from large rather than small
      samples of evidence. In Experiment 1, children exhibited the SSP when exemplars
      were presented sequentially but not when exemplars were presented simultaneously.
      Results from Experiment 3 suggest that the advantage of sequential presentation
      is not due to the additional time to process the available input from the two
      samples but instead may be linked to better memory for specific individuals in
      the large sample. In addition, findings from Experiments 1 and 2 suggest that
      adherence to the SSP is mediated by the disparity between presented samples.
      Overall, these results reveal that the SSP appears early in development and is
      guided by basic cognitive processes triggered during the acquisition of input. 

PMID- 24439114
TI  - Clonal heterogeneity of thymic B cells from early-onset myasthenia gravis
      patients with antibodies against the acetylcholine receptor.
AB  - Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR
      MG) is considered as a prototypic autoimmune disease. The thymus is important in
      the pathophysiology of the disease since thymus hyperplasia is a characteristic
      of early-onset AChR-MG and patients often improve after thymectomy. We
      hypothesized that thymic B cell and antibody repertoires of AChR-MG patients
      differ intrinsically from those of control individuals. Using immortalization
      with Epstein-Barr Virus and Toll-like receptor 9 activation, we isolated and
      characterized monoclonal B cell lines from 5 MG patients and 8 controls. Only 2
      of 570 immortalized B cell clones from MG patients produced antibodies against
      the AChR (both clones were from the same patient), suggesting that AChR-specific
      B cells are not enriched in the thymus. Surprisingly, many B cell lines from both
      AChR-MG and control thymus samples displayed reactivity against striated muscle
      proteins. Striational antibodies were produced by 15% of B cell clones from AChR
      MG versus 6% in control thymus. The IgVH gene sequence analysis showed remarkable
      similarities, concerning VH family gene distribution, mutation frequency and CDR3
      composition, between B cells of AChR-MG patients and controls. MG patients showed
      clear evidence of clonal B cell expansion in contrast to controls. In this latter
      aspect, MG resembles multiple sclerosis and clinically isolated syndrome, but
      differs from systemic lupus erythematosus. Our results support an antigen driven
      immune response in the MG thymus, but the paucity of AChR-specific B cells, in
      combination with the observed polyclonal expansions suggest a more diverse immune
      response than expected. 

PMID- 24439116
TI  - Is laparoscopic single-stage biliopancreatic diversion with duodenal switch safe
      in super morbidly obese patients?
AB  - BACKGROUND: It has been hypothesized that the morbidity and mortality of
      laparoscopic biliopancreatic diversion with duodenal switch (BPD-DS) are likely
      to increase with increasing body mass index (BMI), especially with BMI>50
      kg/m(2). Therefore, a 2-stage approach to this procedure has been advocated in
      super morbidly obese patients. The authors hypothesized that a BMI >= 50 kg/m(2)
      does not significantly influence the morbidity and mortality perioperatively
      associated with this procedure. METHODS: A retrospective analysis of all patients
      who underwent laparoscopic BPD-DS between January 2009 and September 2011 was
      performed. The patients were divided into 2 groups: patients with BMI<50 kg/m(2)
      and those with BMI>50 kg/m(2). Patient characteristics, perioperative variables,
      30-day outcomes, and complications were analyzed and compared. RESULTS: A total
      of 226 patients underwent laparoscopic BPD-DS. Mean patient age was 44.9 years
      (range: 20-72 yr). Male to female ratio was 59 to 170 patients (75% versus 25%),
      respectively. Mean BMI was 50.2 kg/m(2) (range: 37.2-68.8 kg/m(2)). A total of
      127 patients had a BMI<50 kg/m(2) (Group 1), and 99 patients had a BMI >= 50
      kg/m(2) (Group 2). The length of procedure in Groups 1 and 2 was 296 minutes and
      287 minutes, respectively (P = .25). The rate of conversion to open BPD-DS was
      1.5% in Group 1 and 3% in Group 2 (P = .65). Two leaks occurred in Group 1; no
      patient in Group 2 developed this complication. One patient in Group 2 developed
      pulmonary embolism. The rates of all other complications resulting in a longer
      length of stay were 11% in Group 1 and 8% in Group 2 (P = .50). The 30-day
      reoperation rate was 3% in Group 1 and 1% in Group 2 (P = .39). The mean length
      of stay was 3.97 days for Group 1 and 3.67 days for Group 2 (P = .34). No
      mortality occurred in this series. CONCLUSION: In the present study, BMI >= 50
      kg/m(2) did not increase intraoperative or postoperative complications at 30 days
      after laparoscopic PBD-DS. No significant differences were noted between patients
      with BMI >= 50 kg/m(2) and patients with BMI<50 kg/m(2). A single-stage
      laparoscopic BPD-DS procedure can be safely offered to the super morbidly obese
      patients.

PMID- 24439117
TI  - Body mass index and diabetes status do not affect postoperative infection rates
      after bariatric surgery.
AB  - BACKGROUND: Obesity predisposes general surgical patients to infections such as
      surgical site infection and respiratory tract infection. The infection rates vary
      by surgical approach and the type of surgery undertaken. Bariatric surgery is
      increasingly used to treat obesity and obesity related co-morbidities. However,
      little is known about the relationship between postoperative infections and
      patient characteristics, such as body mass index (BMI) or diabetes status, in
      bariatric cohorts. The objective of this study was to examine the rates of all
      postoperative infection in patients after bariatric surgery in relation to known
      risk factors. RESULTS: A total of 815 patients were included in the final
      analysis. During the first month after surgery, 5.2% of patients experienced an
      infection-related event, and surgery-related infections were most prevalent.
      Between the second and twelfth month postoperatively, a further 4.7% of patients
      experienced an infection-related event, and nonsurgical related infections were
      most prevalent. Infection was associated with increased length of stay in Roux-en
      Y gastric bypass (RYGB) (P<.001) and sleeve gastrectomy (SG) (P = .011) but not
      in laparoscopic adjustable gastric banding (LAGB) (P = .41). Diabetes status and
      BMI were not associated with increased infection rates during the first month
      after surgery. CONCLUSION: Infection rates after bariatric surgery are relatively
      low and are associated with a prolonged length of hospital stay. Reassuringly,
      neither diabetic status nor BMI appear to increase the risk of postoperative
      infection after bariatric surgery.

PMID- 24439126
TI  - Exploring implicit preventive strategies in prehospital emergency workers: a
      novel approach for preventing back problems.
AB  - INTRODUCTION: Back problems are a major occupational health issue for prehospital
      emergency care professionals. The goals of this article are to: 1) provide
      descriptive data about the prevalence and the severity of lower back and upper
      back disorders in EMTs and paramedics; 2) identify some individual and collective
      strategies used by EMTs and paramedics to protect their health as they perform
      prehospital emergency missions; 3) assess the possible effectiveness of
      strategies in preventing back problems by exploring associations between the use
      of strategies and the presence and severity of symptoms. MATERIAL AND METHODS:
      The method includes a questionnaire survey (sample n = 334; paramedics and
      emergency medical technicians) and ergonomics work practice analysis involving
      shadowing ambulance crews in 12 medical emergency services (over 400 h). RESULTS:
      A majority of ambulance professionals had experienced back pain in the twelve
      month period before the survey. Work practice analysis revealed strategies and
      tricks of the trade used by ambulance professionals to reduce the chances of back
      strain while working. Multiple regression analyses showed that self-reported use
      of such strategies was associated with fewer back symptoms. CONCLUSIONS:
      Preventive strategies should be integrated into specialised training programs for
      prehospital medical emergency professionals. This approach could also be used in
      other work settings.

PMID- 24439118
TI  - [HAS report on vitamin D measurement: don't go from an extreme situation to
      another as extreme situation].

PMID- 24439127
TI  - Effect of the season on some aspects of the estrous cycle in Martina Franca
      donkey.
AB  - The Martina Franca (MF) donkey breed, with 48 jackasses and 515 jennies, is
      considered an endangered breed according to the data from the Monitoring
      Institute for Rare Breeds and Seeds in Europe. The knowledge of the estrous cycle
      characteristics has a great impact for assisted reproduction, especially in
      endangered species. In this study, the estrous cycle characteristics were
      investigated in 12 MF jennies throughout the year. Estrous cycle, estrous and
      diestrous lengths, follicular growth and ovulation, and estradiol-17beta (E2) and
      progesterone (P4) plasma concentrations were monitored in MF jennies and compared
      in different seasons. In all jennies (100%) estrous cycle was detected during the
      whole year, with no differences in the estrous cycle length among seasons.
      However, a significant increase of estrous length in spring and summer compared
      with autumn and winter was found. Diestrus was shorter in summer than in the
      other seasons. Estrous behavior was always shown and characterized by rhythmic
      eversion of the vulvar labia (winking) with exhibition of the clitoris,
      urination, male receptivity and clapping, with sialorrhoea, neck and head
      extension, and back ears. Estrus was characterized by the ovulation of a larger
      follicle in spring and summer than in autumn and winter. The pattern of E2 and P4
      plasma concentrations during the estrous cycle were similar to that reported for
      the mare, but without differences among the four seasons, so that a negligible
      effect of environmental conditions on ovarian E2 and P4 secretion was
      hypothesized, despite the larger diameter of the ovulating follicle in spring and
      summer. 

PMID- 24439128
TI  - Thromboelastographic changes in patients experiencing an acute ischemic stroke
      and receiving alteplase.
AB  - BACKGROUND: Thromboelastography is a method of measuring whole-blood coagulation
      changes and has been used to guide therapy and monitor changes in a variety of
      disease states. However, few studies have investigated the thromboelastographic
      changes experienced in a patient who has received alteplase for an acute ischemic
      stroke. This pilot study sought to describe the effect of alteplase on the
      thromboelastogram tracings of patients experiencing an acute ischemic stroke.
      METHODS: This was an institutional review board-approved prospective cohort
      study. Patients who presented to the emergency department with symptoms of acute
      ischemic stroke and received intravenous alteplase were evaluated for inclusion.
      Blood samples were obtained before alteplase administration and at 30, 60, 90,
      120, and 150 minutes after alteplase administration. In addition, baseline
      variables collected included patient age, sex, prothrombin time, partial
      thromboplastin time, and the use of pretreatment anticoagulants or antiplatelet
      agents. Patients were also followed throughout their hospital stay for
      development of intracranial hemorrhage. RESULTS: A total of 7 patients were
      included in the analysis. At baseline, thromboelastogram parameters of all
      patients were within the normal range. The maximum inhibition of fibrin buildup
      was seen at 30 minutes after the start of alteplase infusion, and the lowest clot
      strength was observed at 60 minutes after initiation of alteplase. Most patients
      return to near baseline parameters within 150 minutes of alteplase initiation;
      however, 2 patients did not return to their baseline values within the 150-minute
      time frame. CONCLUSIONS: Our study suggests that thromboelastogram (TEG) is a
      useful tool for determining changes in the coagulation system of patients whom
      have received recombinant tissue plasminogen activator (rt-PA). Further study is
      needed to determine if TEG can be used to predict those patients who may be at
      higher risk of adverse events because of rt-PA.

PMID- 24439129
TI  - Psychogenic pseudostroke.
AB  - Psychogenic pseudostroke (PS) is when symptoms are suggestive of a stroke, but in
      reality, of psychogenic origin. Most neurologists have encountered a case of such
      nature. However, specific information regarding its prevalence and management is
      scarce. This is a discussion of psychogenic PS vis-a-vis the complexities in its
      diagnosis and management. 

PMID- 24439130
TI  - White matter hyperintensity volume correlates with matrix metalloproteinase-2 in
      acute ischemic stroke.
AB  - BACKGROUND: White matter hyperintensity (WMH), a common radiographic finding
      associated with stroke risk and outcome, has been linked to matrix
      metalloproteinase (MMP) activity and increased levels of oxidative stress in
      nonstroke populations. We sought to determine whether WMH severity is associated
      with plasma levels of MMPs and oxidative stress (F2-isoprostane) in subjects with
      acute ischemic stroke (AIS). METHODS: We measured plasma biomarker levels at
      baseline and 48 hours in consecutive AIS subjects. White matter hyperintensity
      volume (WMHv) was quantified on admission magnetic resonance imaging using a
      validated semiautomated protocol, and Spearman correlation coefficients were
      derived for all measured biomarkers. RESULTS: We enrolled 405 AIS subjects (mean
      age 70+/-15 years; 58% male; median WMHv 3.4 cm3, interquartile range 1.4-9.5).
      WMHv and age were strongly correlated (rho=.57, P<.0001). WMHv and MMP-2 levels
      were correlated at baseline (rho=.23, P<.0001) and at 48 hours poststroke
      (rho=.19, P=.002). In multivariate analysis, 48-hour MMP-2 levels were
      independently associated with WMHv (beta=.12, P=.04). MMP-9 and F2-isioprostane
      levels did not correlate with WMHv. CONCLUSIONS: In AIS patients, MMP-2 levels
      are associated with the pre-existing burden of WMH. If validated, these findings
      may further elucidate the role of MMP-2 in pathophysiology of chronic
      cerebrovascular injury, such as WMH, and in brain susceptibility to acute
      ischemia.

PMID- 24439132
TI  - Penehyclidine hydrochloride inhibits the LPS-induced inflammatory response in
      microglia.
AB  - BACKGROUND: Activated microglia play an important role in neuroinflammation,
      which contributes to the neuronal damage found in many neurodegenerative
      diseases. Penehyclidine hydrochloride (PHC) is an anesthetic used before surgical
      operations, but also exhibits anti-inflammatory effects on the respiratory and
      digestive system. In the present study, we investigated whether PHC produces
      similar anti-inflammatory effects in activated microglia in the central nervous
      system. MATERIALS AND METHODS: Microglial cells were incubated with
      lipopolysaccharide (LPS) in the presence or absence of various concentrations of
      PHC, SB203580 (p38 mitogen-activated protein kinase [MAPK] inhibitor), and
      pyrrolidine dithiocarbamate (nuclear factor-kappa B [NF-kappaB] inhibitor).
      Markers of inflammation and oxidative stress were measured using enzyme-linked
      immunosorbent assay and quantitative real-time polymerase chain reaction. The
      effect of PHC on NF-kappaB activity was assessed with a NF-kappaB p50/p65
      transcription factor assay kit. The involvement of p38 MAPK phosphorylation in
      the anti-inflammatory effects of PHC was evaluated with a specific enzyme-linked
      immunosorbent assay kit for phospho-p38. RESULTS: PHC significantly inhibited the
      release of nitric oxide, prostaglandin E2, interleukin 1beta, and tumor necrosis
      factor alpha while upregulating the expression of inducible nitric oxide synthase
      messenger RNA in LPS-activated microglia. Moreover, PHC effectively inhibited the
      translocation of NF-kappaB from the cytoplasm to the nucleus and the
      phosphorylation of p38 MAPK. The activities of NF-kappaB and p38 MAPK in LPS
      treated microglia were significantly lowered after pretreatment of PHC.
      CONCLUSIONS: PHC inhibited the LPS-induced release of inflammatory mediators in
      microglia. These inhibitory effects of PHC may be mediated by blocking p38 MAPK
      and NF-kappaB pathways in microglia. These preclinical findings may offer a novel
      therapeutic option to confine microglial overactivation in neurodegenerative
      diseases.

PMID- 24439131
TI  - Smoking and mortality in stroke survivors: can we eliminate the paradox?
AB  - BACKGROUND: Many studies have suggested that smoking does not increase mortality
      in stroke survivors. Index event bias, a sample selection bias, potentially
      explains this paradoxical finding. Therefore, we compared all-cause,
      cardiovascular disease (CVD), and cancer mortality by cigarette smoking status
      among stroke survivors using methods to account for index event bias. METHODS:
      Among 5797 stroke survivors of 45 years or older who responded to the National
      Health Interview Survey years 1997-2004, an annual, population-based survey of
      community-dwelling US adults, linked to the National Death Index, we estimated
      all-cause, CVD, and cancer mortality by smoking status using Cox proportional
      regression and propensity score analysis to account for demographic,
      socioeconomic, and clinical factors. Mean follow-up was 4.5 years. RESULTS: From
      1997 to 2004, 18.7% of stroke survivors smoked. There were 1988 deaths in this
      stroke survivor cohort, with 50% of deaths because of CVD and 15% because of
      cancer. Current smokers had an increased risk of all-cause mortality (hazard
      ratio [HR], 1.36; 95% confidence interval [CI], 1.14-1.63) and cancer mortality
      (HR, 3.83; 95% CI, 2.48-5.91) compared with never smokers, after controlling for
      demographic, socioeconomic, and clinical factors. Current smokers had an
      increased risk of CVD mortality controlling for age and sex (HR, 1.29; 95% CI,
      1.01-1.64), but this risk did not persist after controlling for socioeconomic and
      clinical factors (HR, 1.15; 95% CI, .88-1.50). CONCLUSIONS: Stroke survivors who
      smoke have an increased risk of all-cause mortality, which is largely because of
      cancer mortality. Socioeconomic and clinical factors explain stroke survivors'
      higher risk of CVD mortality associated with smoking.

PMID- 24439133
TI  - Design and evaluation of a new ergonomic handle for instruments in minimally
      invasive surgery.
AB  - BACKGROUND: Laparoscopic surgery techniques have been demonstrated to provide
      massive benefits to patients. However, surgeons are subjected to hardworking
      conditions because of the poor ergonomic design of the instruments. In this
      article, a new ergonomic handle design is presented. This handle is designed
      using ergonomic principles, trying to provide both more intuitive manipulation of
      the instrument and a shape that reduces the high-pressure zones in the contact
      with the surgeon's hand. MATERIALS AND METHODS: The ergonomic characteristics of
      the new handle were evaluated using objective and subjective studies. The
      experimental evaluation was performed using 28 volunteers by means of the
      comparison of the new handle with the ring-handle (RH) concept in an instrument
      available on the market. The volunteers' muscle activation and motions of the
      hand, wrist, and arm were studied while they performed different tasks. The data
      measured in the experiment include electromyography and goniometry values.
      RESULTS: The results obtained from the subjective analysis reveal that most
      volunteers (64%) preferred the new prototype to the RH, reporting less pain and
      less difficulty to complete the tasks. The results from the objective study
      reveal that the hyperflexion of the wrist required for the manipulation of the
      instrument is strongly reduced. CONCLUSIONS: The new ergonomic handle not only
      provides important ergonomic advantages but also improves the efficiency when
      completing the tasks. Compared with RH instruments, the new prototype reduced the
      high-pressure areas and the extreme motions of the wrist.

PMID- 24439134
TI  - All-trans-retinoic acid counteract the tumor-stimulating effect of hepatectomy
      and increases survival of rats bearing liver metastases.
AB  - BACKGROUND: We previously demonstrated a stimulating effect of hepatectomy on
      residual tumor cells after resection of liver metastases. The aim of this study
      was to analyze the effect of all-trans-retinoic acid (ATRA) on the protumor
      effect of hepatectomy and survival of hepatectomized rats bearing liver
      metastases. We also explored whether ATRA interfered with the tumor promoting
      effect of hepatotropic growth factors (GFs). METHODS: The in vitro effect of ATRA
      on proliferation of S4MH rhabdomyosarcoma tumor cells was assessed when cultured
      with laparotomized or hepatectomized rat serum (HRS), or in the presence of GFs
      (hepatocyte growth factor, insulin growth factor 2, Platelet Derived Growth
      Factor (PDGF)-BB, and vascular endothelial growth factor). For the in vivo
      studies, rats were partially hepatectomized on day 10 after metastasis induction,
      one group being treated with ATRA from day 7 to 14, and a second receiving
      cyclophosphamide (CY; on days 10 and 14) alone or with ATRA. We determined the
      size and number of liver and lung metastases. Finally, we analyzed the effect of
      treatments on rat survival. RESULTS: Hepatotropic GFs increased cell
      proliferation in a similar manner to HRS. In vitro, ATRA blocked the protumor
      effect of both HRS and GFs. In vivo, ATRA reduced the size and number of liver
      and lung metastases, and significantly increased rat survival. Furthermore,
      adding ATRA to CY significantly increased survival compared with CY alone.
      CONCLUSIONS: In our model, ATRA minimizes the tumor-stimulating effect of
      hepatectomy, reducing the number and size of liver metastases and improving
      survival. The results suggest that the ATRA may be useful for blocking the growth
      promoting effect of hepatotropic GFs released after liver metastasis resection.

PMID- 24439135
TI  - Pharmacologic evidence for role of endothelial nitric oxide synthase in
      neuroprotective mechanism of ischemic postconditioning in mice.
AB  - BACKGROUND: The present study was conducted to pharmacologically investigate the
      isoform-specific role of nitric oxide pathway in neuroprotective mechanism of
      ischemic postconditioning (iPoCo). MATERIALS AND METHODS: Bilateral carotid
      artery occlusion of 12 min followed by reperfusion for 24 h was used to produce
      ischemia- and reperfusion-induced cerebral injury in male Swiss mice. Memory was
      assessed using Morris water maze test. Degree of motor in-coordination was
      evaluated using inclined beam-walk test, rotarod test, and lateral push test.
      Cerebral infarct size was measured using triphenyltetrazolium chloride staining.
      Brain acetylcholinestrase activity, thiobarbituric acid-reactive species,
      nitrite/nitrate, and reduced glutathione levels were also estimated. Western
      blotting was performed to determine endothelial nitric oxide synthase (eNOS)
      expression. RESULTS: Bilateral carotid artery occlusion followed by reperfusion
      produced significant rise in cerebral infarct size, acetylcholinesterase
      activity, and thiobarbituric acid-reactive species levels along with fall in
      nitrite/nitrate, and glutathione and eNOS expression levels. A significant
      impairment of memory and motor coordination was also noted. iPoCo consisting of
      three episodes of 10-s carotid artery occlusion and reperfusion significantly
      attenuated infarct size, memory impairment, motor in-coordination, altered
      biochemicals, and protein expression levels. iPoCo-induced neuroprotective
      effects were significantly abolished by L-NAME (a nonselective nitric oxide
      synthase inhibitor) and L-NIO (a selective eNOS inhibitor). However,
      aminoguanidine (a selective inducible nitric oxide synthase inhibitor) and 7
      nitroindazole (a selective neuronal nitric oxide synthase inhibitor) did not
      modulate beneficial effects of iPoCo. CONCLUSIONS: It may be concluded that
      nitric oxide pathway probably plays a vital role with specific involvement of
      eNOS in neuroprotective mechanism of iPoCo.

PMID- 24439136
TI  - Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot
      infections with and without osteomyelitis.
AB  - A phase 3, randomized, double-blind trial was conducted in subjects with diabetic
      foot infections without osteomyelitis (primary study) or with osteomyelitis
      (substudy) to determine the efficacy and safety of parenteral (intravenous [iv])
      tigecycline (150 mg once-daily) versus 1 g once-daily iv ertapenem +/-
      vancomycin. Among 944 subjects in the primary study who received >=1 dose of
      study drug, >85% had type 2 diabetes; ~90% had Perfusion, Extent, Depth/tissue
      loss, Infection, and Sensation infection grade 2 or 3; and ~20% reported prior
      antibiotic failure. For the clinically evaluable population at test-of-cure,
      77.5% of tigecycline- and 82.5% of ertapenem +/- vancomycin-treated subjects were
      cured. Corresponding rates for the clinical modified intent-to-treat population
      were 71.4% and 77.9%, respectively. Clinical cure rates in the substudy were low
      (<36%) for a subset of tigecycline-treated subjects with osteomyelitis. Nausea
      and vomiting occurred significantly more often after tigecycline treatment (P =
      0.003 and P < 0.001, respectively), resulting in significantly higher
      discontinuation rates in the primary study (nausea P = 0.007, vomiting P <
      0.001). In the primary study, tigecycline did not meet criteria for
      noninferiority compared with ertapenem +/- vancomycin in the treatment of
      subjects with diabetic foot infections. 

PMID- 24439137
TI  - Mycobacterium leprae and Mycobacterium haemophilum co-infection in an
      iatrogenically immunosuppressed patient.
AB  - We present the case of a native Texan who was diagnosed with tuberculoid leprosy
      and later developed a cutaneous infection with M. haemophilum following
      iatrogenic immunosuppression. To our knowledge, there are no such reports of M.
      haemophilum and M. leprae infection occurring simultaneously in the same host. 

PMID- 24439138
TI  - Use and characteristics of electronic health record systems among office-based
      physician practices: United States, 2001-2013.
AB  - KEY FINDINGS: In 2013, 78% of office-based physicians used any type of electronic
      health record (EHR) system, up from 18% in 2001. In 2013, 48% of office-based
      physicians reported having a system that met the criteria for a basic system, up
      from 11% in 2006. The percentage of physicians with basic systems by state ranged
      from 21% in New Jersey to 83% in North Dakota. In 2013, 69% of office-based
      physicians reported that they intended to participate (i.e., they planned to
      apply or already had applied) in "meaningful use" incentives. About 13% of all
      office-based physicians reported that they both intended to participate in
      meaningful use incentives and had EHR systems with the capabilities to support 14
      of the Stage 2 Core Set objectives for meaningful use. From 2010 (the earliest
      year that trend data are available) to 2013, physician adoption of EHRs able to
      support various Stage 2 meaningful use objectives increased significantly. The
      Health Information Technology for Economic and Clinical Health (HITECH) Act of
      2009 authorized incentive payments to increase physician adoption of electronic
      health record (EHR) systems (1,2). The Medicare and Medicaid EHR Incentive
      Programs are staged in three steps, with increasing requirements for
      participation. To receive an EHR incentive payment, physicians must show that
      they are "meaningfully using" certified EHRs by meeting certain objectives (3,4).
      This report describes trends in the adoption of EHR systems from 2001 through
      2013, as well as physicians' intent to participate in the EHR Incentive Programs
      and their readiness to meet 14 of the Stage 2 Core Set objectives for meaningful
      use in 2013.

PMID- 24439141
TI  - Wedding-related weight change: the ups and downs of love.
AB  - The present study examined wedding-related weight change in 343 brides recruited
      from Bridal Expos in South Australia. Demographic measures and questions about
      weight were assessed over three time points: upon entry into the study (n=343), 1
      month pre-wedding (n=130), and 6-months post-wedding (n=112). Although close to
      50% of brides-to-be indicated a desire to lose weight before their weddings,
      linear mixed modelling revealed that their average weight did not change in the
      lead up to their wedding. However, 6 months after their wedding, participants had
      gained approximately 2kg. In addition, women who had been told to lose weight
      before their wedding gained significantly more weight post-wedding compared to
      participants who had not been told to lose weight. The findings demonstrate that
      wedding-related weight change may be an important factor in the body image of
      newlyweds and clinicians should be mindful of potential body dissatisfaction
      associated with post-wedding weight gain. 

PMID- 24439145
TI  - Outcomes of acute ischemic stroke patients following endovascular intervention:
      role and clinical utility of transcranial Doppler.

PMID- 24439144
TI  - Within-day variability on short and long walking tests in persons with multiple
      sclerosis.
AB  - OBJECTIVE: To compare within-day variability of short (10 m walking test at usual
      and fastest speed; 10MWT) and long (2 and 6-minute walking test; 2MWT/6MWT) tests
      in persons with multiple sclerosis. DESIGN: Observational study. SETTING: MS
      rehabilitation and research centers in Europe and US within RIMS (European
      network for best practice and research in MS rehabilitation). SUBJECTS:
      Ambulatory persons with MS (Expanded Disability Status Scale 0-6.5).
      INTERVENTION: Subjects of different centers performed walking tests at 3 time
      points during a single day. MAIN MEASURES: 10MWT, 2MWT and 6MWT at fastest speed
      and 10MWT at usual speed. Ninety-five percent limits of agreement were computed
      using a random effects model with individual pwMS as random effect. Following
      this model, retest scores are with 95% certainty within these limits of baseline
      scores. RESULTS: In 102 subjects, within-day variability was constant in absolute
      units for the 10MWT, 2MWT and 6MWT at fastest speed (+/-0.26, 0.16 and 0.15m/s
      respectively, corresponding to +/-19.2m and +/-54 m for the 2MWT and 6MWT)
      independent on the severity of ambulatory dysfunction. This implies a greater
      relative variability with increasing disability level, often above 20% depending
      on the applied test. The relative within-day variability of the 10MWT at usual
      speed was +/-31% independent of ambulatory function. CONCLUSIONS: Absolute values
      of within-day variability on walking tests at fastest speed were independent of
      disability level and greater with short compared to long walking tests. Relative
      within-day variability remained overall constant when measured at usual speed.

PMID- 24439146
TI  - Change is our challenge and our opportunity.

PMID- 24439147
TI  - Leadership advice from a PGY-46.

PMID- 24439148
TI  - Mesenchymal stem cell therapies in the treatment of musculoskeletal diseases.
AB  - The application of regenerative strategies to musculoskeletal ailments offers
      extraordinary promise to transform management of the conditions of numerous
      patients. The use of cell-based therapies and adjunct strategies is under active
      investigation for injuries and illnesses affecting bones, joints, tendons, and
      skeletal muscle. Of particular interest to the field is the mesenchymal stem
      cell, an adult stem cell found in bone marrow and adipose tissue. This cell type
      can be expanded ex vivo, has allogeneic application, and has the capacity for
      engraftment and differentiation into mesodermal lineages. Also of major interest
      in the field is the use of platelet-rich plasma, a strategy to concentrate
      endogenous cytokines and growth factors with reparative potential. Here we review
      the biological basis, clinical studies, safety, and current state of mesenchymal
      stem cell and platelet-rich plasma therapies in the treatment of musculoskeletal
      disease. 

PMID- 24439149
TI  - Clinical challenges and opportunities of mesenchymal stem cells in
      musculoskeletal medicine.
AB  - The use of stem cells in orthopedics has been researched for many years, with
      robust animal data that show efficacy in cartilage healing, tendon repair, and
      intervertebral disk treatment. Early clinical data are also just starting to be
      published, and these results are encouraging. Safety data in large case series,
      some that lasted for many years, have also been published. The field of tissue
      engineering with stem cells in musculoskeletal impairments has the potential to
      reduce morbidity and improve clinical outcomes. The regulatory environment for
      this area of medicine is still developing. 

PMID- 24439150
TI  - Did we reach too far? The opioid epidemic and chronic pain.

PMID- 24439151
TI  - Do physiatric procedures represent a value or liability?

PMID- 24439152
TI  - Treatment of pain in SAPHO (synovitis, acne, pustulosis, hyperostosis, and
      osteitis) syndrome.
AB  - SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes
      a variety of musculoskeletal disorders and associated skin conditions. Diagnosis
      can be difficult but should be considered in the differential in patients with
      lytic, sclerotic, or hyperostotic bone lesions and pain. Appropriate and prompt
      treatment, including use of nonsteroidal medications such as ibuprofen or
      naproxen, colchicine, corticosteroids, and bisphosphonates, and use of disease
      modifying agents such as methotrexate, sulfasalazine and infliximab, can produce
      improvement of symptoms. Multidisciplinary care, including the disciplines of
      rheumatology and dermatology, should be considered. 

PMID- 24439153
TI  - Dual diagnosis: rheumatoid arthritis and multiple sclerosis.
AB  - Juvenile rheumatoid arthritis (JRA) is the most common rheumatologic disease in
      children. Moreover, multiple sclerosis (MS) is the most frequent demyelinating
      disease and has been associated with various chronic inflammatory diseases.
      However, its association with JRA has not been frequently described. Autoimmunity
      in both JRA and MS has been documented in the scientific literature, although
      there has been no definitive finding that patients with JRA are prone to the
      development of MS. An increasing frequency of MS resulting from an increased use
      of antitumor necrosis factor agents in the treatment of rheumatoid arthritis and
      other chronic inflammatory diseases has been reported recently. In this study, we
      report on the development of MS in a patient with JRA who did not have a history
      of antitumor necrosis factor use. 

PMID- 24439154
TI  - Complex suicide with homemade nicotine patches.
AB  - Suicide by self-poisoning is rather common around the world. This paper presents
      an exceptional complex suicide in which nicotine was applied in the form of self
      made patches soaked with an extraction from fine-cut tobacco. In addition, the 51
      year-old suicide victim took a lethal dose of diphenhydramine. Toxicological
      analysis also revealed the presence of tetrazepam in subtherapeutic
      concentrations. The scene of death suggested an autoerotic accident at first, as
      the body was tied with tapes, cables and handcuffs. As a result of the entire
      investigations, the fatality had to be classified as a suicidal intoxication by
      nicotine and diphenhydramine. 

PMID- 24439155
TI  - Sex determination from the mandibular ramus flexure of Koreans by discrimination
      function analysis using three-dimensional mandible models.
AB  - It has been known that mandible ramus flexure is an important morphologic trait
      for sex determination. However, it will be unavailable when mandible is
      incomplete or fragmented. Therefore, the anthropometric analysis on incomplete or
      fragmented mandible becomes more important. The aim of this study is to
      investigate the sex-discriminant potential of mandible ramus flexure on the
      Korean three-dimensional (3D) mandible models with anthropometric analysis. The
      sample consists of 240 three dimensional mandibular models obtained from Korean
      population (M:F; 120:120, mean age 46.2 y), collected by The Catholic Institute
      for Applied Anatomy, The Catholic University of Korea. Anthropometric information
      about 11 metric was taken with Mimics, anthropometry libraries toolkit. These
      parameters were subjected to different discriminant function analyses using SPSS
      17.0. Univariate analyses showed that the resubstitution accuracies for sex
      determination range from 50.4 to 77.1%. Mandibular flexure upper border (MFUB),
      maximum ramus vertical height (MRVH), and upper ramus vertical height (URVH)
      expressed the greatest dimorphism, 72.1 to 77.1%. Bivariate analyses indicated
      that the combination of MFUB and MRVH hold even higher resubstitution accuracy of
      81.7%. Furthermore, the direct and stepwise discriminant analyses with the
      variables on the upper ramus above flexure could predict sex in 83.3 and 85.0%,
      respectively. When all variables of mandibular ramus flexure were input in
      stepwise discriminant analysis, the resubstitution accuracy arrived as high as
      88.8%. Therefore, we concluded that the upper ramus above flexure hold the larger
      potentials than the mandibular ramus flexure itself to predict sexes, and that
      the equations in bivariate and multivariate analysis from our study will be
      helpful for sex determination on Korean population in forensic science and law.

PMID- 24439156
TI  - Health status and health resource use among long-term survivors of breast,
      colorectal and prostate cancer.
AB  - INTRODUCTION: The growing number of long-term cancer survivors poses a new
      challenge to health care systems. In Spain, follow-up is usually carried out in
      oncology services, but knowledge of cancer survivors' health care needs in this
      context is limited. The purpose of this study was to ascertain the health status
      of long-term survivors of breast, prostate, and colorectal cancer and to
      characterize their use of health care services. METHODS: Retrospective
      multicenter cohort study. We collected data from patients' clinical histories and
      through telephone interviews, using a specially designed questionnaire that
      included the SF-36v2 Quality of Life and Nottingham Health Profile scales.
      RESULTS: The questionnaire was completed by 51.2% (n= 583) of the potential
      sample. No significant differences were observed between 5-year and 10-year
      survivors. Overall, more than 80% of respondents were undergoing drug treatment
      for morbidity related to advanced age. Quality of life was good in most patients,
      and cancer-related morbidity was low and of little complexity. For the most part,
      participants reported using primary care services for care of chronic diseases
      and opportunistic treatment of sequelae related to the cancer treatment.
      Oncological follow-up was centralized at the hospital. CONCLUSIONS: Survivors of
      breast, prostate and colorectal cancer with tumoral detection at an early stage
      and without recurrences or second neoplasms experienced little morbidity and
      enjoyed good quality of life. This study proposes exploration of a follow-up
      model in the Spanish health system in which primary care plays a more important
      role than is customary in cancer survivors in Spain.

PMID- 24439157
TI  - Massive panniculectomy results in improved functional outcome.
AB  - BACKGROUND: Panniculus morbidus is a large abdominal apron found in morbidly
      obese patients. This condition creates a vicious cycle of weight gain and
      functional incapacity. Our study assessed the functional improvement in patients
      undergoing massive panniculectomy. METHODS: A retrospective review of
      panniculectomies performed from 1994 to 2012 was conducted. Twenty-seven patients
      with resections >20 lbs were selected. Data on demographics, operative details,
      complications, and pre- and postoperative functional capacity (using the
      Steinbrocker Functional Classification) were collected. RESULTS: The preoperative
      mean body mass index was 58 kg/m(2), with a mean resection weight of 33 lbs. The
      overall complication rate was 74%. A statistically significant improvement in
      functional capacity (preop mean 3.7 vs postop mean 2.0; P < .0001) was
      identified. CONCLUSIONS: Panniculus morbidus is a functionally debilitating
      condition and massive panniculectomy is often the only treatment available. Our
      data suggest that massive panniculectomy is a viable option for patients
      functionally incapacitated by panniculus morbidus.

PMID- 24439158
TI  - Obstructive sleep apnea in general surgery patients: is it more common than we
      think?
AB  - BACKGROUND: To determine the risk of obstructive sleep apnea (OSA) in
      preoperative surgical patients. METHODS: Three hundred seventy-one new patients
      presenting to an outpatient general surgery clinic were prospectively screened
      for risk of OSA using the STOP-Bang questionnaire. Patients were classified as
      high risk with a score of >3 on the STOP-Bang questionnaire. Polysomnography
      results were reviewed when available. RESULTS: Complete questionnaires were
      available on 367 (98.9%) patients. Two hundred thirty-seven patients (64.6%) were
      classified as high risk of OSA on the questionnaire. Polysomnography results
      available on 49 patients revealed severe OSA in 17 (34.5%), moderate in 8
      (16.5%), mild in 14 (28.5%), and no OSA in 10 (20.5%) patients. The positive
      predictive value and sensitivity of the questionnaire were 76%, and 92% for the
      STOP-Bang questionnaire, respectively. The sensitivity increased to 100% for
      severe OSA. CONCLUSION: Preoperative screening for OSA should be considered to
      diagnose patients at risk.

PMID- 24439159
TI  - Trauma recidivists: surprisingly better outcomes than initially injured trauma
      patients.
AB  - BACKGROUND: The purpose of this study was to determine if there was a difference
      in hospital outcomes between trauma recidivists (RCID) and nonrecidivists
      (NRCID). METHODS: Outcomes of RCID and NRCID were compared. A recidivist was
      defined as a patient with a history of hospital evaluation for injury within the
      prior 5 years. Patients with good functional status had a Glasgow Outcome Score
      of 4 to 5. RESULTS: Of the 2,127 patients admitted, 466 (22%) were RCID. NRCID
      were more likely to have Injury Severity Score >25 (12% vs 8.6%; P = .04) than
      RCID. Eighty-eight percent of RCID were discharged with a good functional status
      compared with 83% of RCID (P = .02). NRCID were more likely to be admitted to a
      critical care unit (43% vs 36%; P = .01), but there was no significant difference
      in hospital mortality. CONCLUSION: RCID were less severely injured and had better
      hospital outcomes than NRCID.

PMID- 24439160
TI  - Predicting the unpredictable: comparing readmitted versus non-readmitted
      colorectal surgery patients.
AB  - BACKGROUND: To evaluate readmissions to determine predictors and patterns of
      readmission. METHODS: Prospective database review identified readmitted and non
      readmitted patients after colorectal surgery. Variables for the index and
      readmission episode were examined. RESULTS: A total of 212 readmissions and 3,292
      nonreadmissions were analyzed. The majority was elective. Readmitted patients
      were older (P = .003), had more comorbidities (P < .0001), longer operative times
      (P < .0001), length of stay (P < .0001), and higher costs (P = .002). At the time
      of discharge, more readmitted patients required temporary nursing (P < .0001).
      Independent readmission predictors were higher American Society of
      Anesthesiologists score, previous abdominal operation, intensive care unit stay,
      and dysmotility/constipation surgery. At the time of readmission, 29.2% required
      reoperation. More than half had an open procedure initially (55.2%). After
      initial open procedures, reoperative time (P = .05) and LOS were longer (P =
      .028), and more patients required temporary nursing care at the time of discharge
      (P = .046). Readmissions caused an additional mean hospital cost of $12,670.89.
      CONCLUSIONS: Readmitted patients have distinct demographic and outcomes
      variables. As most were elective cases, stratifying patients preoperatively may
      enable perioperative planning for this higher risk group.

PMID- 24439161
TI  - Final analysis of the pilot trial of diaphragm pacing in amyotrophic lateral
      sclerosis with long-term follow-up: diaphragm pacing positively affects diaphragm
      respiration.
AB  - BACKGROUND: Respiratory insufficiency is the major cause of mortality in patients
      with amyotrophic lateral sclerosis or Lou Gehrig's disease. This is the final
      report of the diaphragm pacing (DP) pilot trial. METHODS: Patients underwent
      laparoscopic diaphragm electrode implantations and subsequent conditioning of
      diaphragms. Serial respiratory function tests were performed in the initial year
      and followed until death. RESULTS: Sixteen patients were implanted with no
      perioperative or unanticipated device-related adverse events. There were 452
      implant-months of follow-up. DP allowed greater movement of the diaphragm under
      fluoroscopy, increased muscle thickness, and decreased the decline in forced
      vital capacity. Median survival from implant was 19.7 months with the cause of
      death respiratory in only 31%. CONCLUSIONS: Long-term analysis of DP in
      amyotrophic lateral sclerosis showed no safety issues and can positively
      influence diaphragm physiology and survival. This formed the initial basis for
      subsequent US Food and Drug Administration approval.

PMID- 24439162
TI  - D-aspartate affects NMDA receptor-extracellular signal-regulated kinase pathway
      and upregulates androgen receptor expression in the rat testis.
AB  - Previous studies have demonstrated that D-aspartic acid (D-Asp) has a role in
      regulating the release and synthesis of testosterone in rats. In this study, we
      investigated the molecular pathway by which this amino acid triggers its action
      in the rat testis. We found expression of N-Methyl-D-Aspartic Acid (NMDA)
      receptor messenger RNAs for NR1, NR2A, and NR2D receptor subunits. After D-Asp
      administration, NR1 and NR2A messenger RNA levels were significantly higher than
      those of controls, whereas NR2D levels remained unchanged. Expression of
      extracellular signal-regulated kinase (ERK) 1 protein was higher than that of
      ERK2 protein in the testis of both D-Asp-treated rats and controls. D-Asp
      administration increased testis levels of both phosphorylated ERK (P-ERK) 1 and
      2. Using immunohistochemical technique, NR1 and P-ERK 1 or 2 proteins were
      preferentially localized within the spermatogonia. Moreover, D-Asp administration
      increased both serum and testis testosterone levels but not estradiol levels.
      Finally, in D-Asp-treated rats, testicular androgen receptor protein levels were
      significantly increased, whereas both estrogen receptor alpha and P-450 aromatase
      levels were significantly decreased. Conclusively, our results, besides
      strengthening the evidence that D-Asp administration in rats induces testosterone
      synthesis, demonstrate for the first time that D-Asp (1) induces testicular NMDA
      receptor-ERK pathway, (2) upregulates androgen receptor expression, and (3)
      downregulates estrogen receptor expression.

PMID- 24439163
TI  - The impact of exposure to serum lipids during in vitro culture on the
      transcriptome of bovine blastocysts.
AB  - In vitro culture has a detrimental impact on early embryonic development, and
      serum addition to IVC is recognized to compromise blastocyst quality.
      Particularly, serum fatty acids affect embryonic lipid composition and reduce
      cryopreservation survival. To understand the molecular pathways of serum-induced
      embryonic stress, this study examined the early development of bovine embryos
      produced in different protein- or lipid-supplemented culture media: BSA alone
      (control), BSA + serum lipid fraction (SELF), delipidated serum and total serum.
      These protein-lipid treatments were applied from the eight to 16 cell stages to
      the blastocyst stage. As planned, SELF treatment increased the fatty acid
      concentration in the medium compared with control medium but did not induce
      embryo toxicity. However, microarray comparison between blastocysts cultured in
      BSA without or with SELF revealed differential transcriptomic profile associated
      with ceramide-induced oxidative stress and inflammation. Moreover, the SELF
      treatment had a significant impact on genes involved in cholesterol metabolism
      (LDLR, HMGCS1), with the potential upstream control of the transcription factors
      SREBP and PPARA, two major regulators of cholesterol metabolism. In addition, the
      expression of pluripotence-related genes (APEX, CLDN6) was downregulated in
      blastocysts subjected to either SELF or total serum. Taken together, these
      results illustrate how the early embryonic transcriptome responds to increased
      lipid exposure through an inflammatory and metabolic signature.

PMID- 24439164
TI  - Setting up equine embryo gender determination by preimplantation genetic
      diagnosis in a commercial embryo transfer program.
AB  - Preimplantation genetic diagnosis (PGD) allows identifying genetic traits in
      early embryos. Because in some equine breeds, like Polo Argentino, females are
      preferred to males for competition, PGD can be used to determine the gender of
      the embryo before transfer and thus allow the production of only female
      pregnancies. This procedure could have a great impact on commercial embryo
      production programs. The present study was conducted to adapt gender selection by
      PGD to a large-scale equine embryo transfer program. To achieve this, we studied
      (i) the effect on pregnancy rates of holding biopsied embryos for 7 to 10 hours
      in holding medium at 32  degrees C before transfer, (ii) the effect on pregnancy
      rates of using embryos of different sizes for biopsy, and (iii) the efficiency of
      amplification by heating biopsies before polymerase chain reaction. Equine
      embryos were classified by size (<=300, 300-1000, and >1000 MUm), biopsied, and
      transferred 1 to 2 or 7 to 10 hours after flushing. Some of the biopsy samples
      obtained were incubated for 10 minutes at 95  degrees C and the rest remained
      untreated. Pregnancy rates were recorded at 25 days of gestation; fetal gender
      was determined using ultrasonography and compared with PGD results. Holding
      biopsied embryos for 7 to 10 hours before transfer produced pregnancy rates
      similar to those for biopsied embryos transferred within 2 hours (63% and 57%,
      respectively). These results did not differ from pregnancy rates of nonbiopsied
      embryos undergoing the same holding times (50% for 7-10 hours and 63% for 1-2
      hours). Pregnancy rates for biopsied and nonbiopsied embryos did not differ
      between size groups or between biopsied and nonbiopsied embryos within the same
      size group (P > 0.05). Incubating biopsy samples for 10 minutes at 95  degrees C
      before polymerase chain reaction significantly increased the diagnosis rate
      (78.5% vs. 45.5% for treated and nontreated biopsy samples respectively). Gender
      determination using incubated biopsy samples matched the results obtained using
      ultrasonography in all pregnancies assessed (11/11, 100%); untreated biopsy
      samples were correctly diagnosed in 36 of 41 assessed pregnancies (87.8%),
      although the difference between treated and untreated biopsy samples was not
      significant. Our results demonstrated that biopsied embryos can remain in holding
      medium before being transferred, until gender diagnosis by PGD is complete (7-10
      hours), without affecting pregnancy rates. This simplifies the management of an
      embryo transfer program willing to incorporate PGD for gender selection, by
      transferring only embryos of the desired sex. Embryo biopsy can be performed in a
      clinical setting on embryos of different sizes, without affecting their
      viability. Additionally, we showed that pretreating biopsy samples with a short
      incubation at 95  degrees C improved the overall efficiency of embryo sex
      determination.

PMID- 24439165
TI  - Endometrial inflammation and abnormal expression of extracellular matrix proteins
      induced by Mycoplasma bovis in dairy cows.
AB  - Mycoplasma bovis infection can cause endometrial inflammation leading to
      infertility and involuntary culling in dairy cows. Because extracellular matrix
      (ECM) proteins affect the adherence of mycoplasma to eukaryotic cell surface,
      they may play a role in the pathogenesis of the bacteria. The objective of the
      present study was to evaluate the endometrial inflammatory response and ECM
      protein expression induced by M bovis. Endometrial concentrations of inflammatory
      cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and
      mRNA and protein expression of collagen IV (CL-IV), fibronectin (FN), and laminin
      (LN) were evaluated 10, 20, and 30 days after M bovis intrauterine infusion in
      breed cows 18 days postpartum. The presence of the bacteria in the uterus was
      detected by nested polymerase chain reaction and denaturing gradient gel
      electrophoresis. Endometrial TNF-alpha, IL-1beta, and IL-6 concentrations in the
      treatment group were greater (P < 0.05) than in the positive and negative control
      groups 20 and 30 days after infusion. Endometrial CL-IV, FN, and LN mRNA and
      protein expression increased (P < 0.01) 20 days after infusion in all groups.
      However, the increase was more pronounced in the treatment group and reactive
      expressions were greater (P < 0.05) than in the positive and negative control
      groups 10, 20, and 30 days after infusion. In conclusion, M bovis triggered
      endometrial inflammatory response and increased CL-IV, FN, and LN mRNA and
      protein expression. The abnormal expression of ECM these proteins may promote the
      pathogenic effects of M bovis that lead to endometrial tissue damage and
      infertility. 

PMID- 24439166
TI  - Familial benign frontotemporal deterioration with C9ORF72 hexanucleotide
      expansion.
AB  - BACKGROUND: In recent years, a benign variant of frontotemporal lobar
      degeneration (FTLD) has been recognized, with a particularly slow progression of
      cognitive deficits and scarce frontotemporal atrophy or hypoperfusion in
      neuroimaging studies. Patients with FTLD have been considered "phenocopies," with
      an underlying nondegenerative neurologic process. RESULTS: We report the first
      family with three affected members having benign FTLD associated with C9ORF72
      gene hexanucleotide expansion. Onset of symptoms occurred during the fifth
      decade, with naming and memory problems as the main features. Two siblings have
      stabilized at mild cognitive impairment or incipient dementia for more than a
      decade, and remain quite independent for their activities of daily living at the
      current ages of 69 and 65 years, respectively. Their mother's cognitive
      deterioration evolved slowly during >30 years. CONCLUSION: This family
      demonstrates that a benign evolution can be part of the growing spectrum of
      clinical phenotypes associated with neurodegenerative diseases caused by the
      C9ORF72 hexanucleotide expansion. Screening of this genetic marker should be
      considered in cases with this slow deterioration, especially if there is a family
      history.

PMID- 24439167
TI  - Increased CSF alpha-synuclein levels in Alzheimer's disease: correlation with tau
      levels.
AB  - BACKGROUND: Given the difficult clinical differential diagnosis between
      Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), growing interest
      resulted in research on alpha-synuclein as a potential cerebrospinal fluid
      biomarker (CSF) for synucleinopathies. METHODS: CSF alpha-synuclein-140
      concentrations were determined by a prototype xMAPTM bead-based assay
      (Innogenetics NV, Belgium). In addition, CSF amyloid beta1-42 (Abeta1-42), total
      tau (T-tau), and phosphorylated tau (P-tau181P) levels were determined. RESULTS:
      CSF alpha-synuclein levels were higher in AD patients as compared with
      cognitively healthy controls (P=.019) and patients with synucleinopathies
      (P<.001). CSF alpha-synuclein levels were correlated with T-tau (P<.001) and P
      tau181P (P<.001) levels in autopsy-confirmed AD patients. A diagnostic algorithm
      using alpha-synuclein and P-tau181P discriminated neuropathologically confirmed
      AD from DLB patients, resulting in sensitivity and specificity values of 85% and
      81%, respectively. CONCLUSION: Because CSF alpha-synuclein levels were
      significantly higher in AD as compared with synucleinopathies, alpha-synuclein
      might have a value as a biomarker for differential dementia diagnosis.

PMID- 24439169
TI  - Microvascular network alterations in the retina of patients with Alzheimer's
      disease.
AB  - BACKGROUND: Although cerebral small-vessel disease has been implicated in the
      development of Alzheimer's disease (AD), the cerebral microcirculation is
      difficult to visualize directly in vivo. Because the retina provides a
      noninvasive window to assess the microcirculation, we determined whether
      quantitatively measured retinal microvascular parameters are associated with AD.
      METHODS: We conducted a case-control study (case:control matching ~ 1:2). Retinal
      photographs were analyzed using a computer program, and a spectrum of
      quantitative retinal microvascular parameters (caliber, fractal dimension,
      tortuosity, and bifurcation) were measured. Logistic regression models were used
      to compute the odds ratio (OR) and 95% confidence interval for AD adjusting for
      age, gender, ethnicity, smoking, hypertension, diabetes, hypercholesterolemia,
      and history of myocardial infarction. RESULTS: We included 136 demented patients
      with AD and 290 age-gender-race-matched controls. Persons with narrower venular
      caliber (OR per standard deviation [SD] decrease, 2.01 [1.27-3.19]), decreased
      arteriolar and venular fractal dimension (OR per SD decrease 1.35 [1.08-1.68],
      1.47 [1.17-1.84], respectively) and increased arteriolar and venular tortuosity
      (OR per SD increase, 1.84 [1.40-2.31], 1.94 [1.48-2.53], respectively) were more
      likely to have AD. These associations still persisted when only AD cases without
      a history of cerebrovascular disease were included. CONCLUSIONS: Patients with AD
      have altered microvascular network in the retina (narrower retinal venules and a
      sparser and more tortuous retinal vessels) compared with matched nondemented
      controls. These changes in retinal microvasculature may reflect similar
      pathophysiological processes in cerebral microvasculature in the brains of
      patients with AD.

PMID- 24439168
TI  - The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on
      expression of TOMM40 and apolipoprotein E genes.
AB  - BACKGROUND: We investigated the genomic region spanning the Translocase of the
      Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes,
      that has been associated with the risk and age of onset of late-onset Alzheimer's
      disease (LOAD) to determine whether a highly polymorphic, intronic poly-T within
      this region (rs10524523; hereafter, 523) affects expression of the APOE and
      TOMM40 genes. Alleles of this locus are classified as S, short; L, long; and VL,
      very long based on the number of T residues. METHODS: We evaluated differences in
      APOE messenger RNA (mRNA) and TOMM40 mRNA levels as a function of the 523
      genotype in two brain regions from APOE epsilon3/epsilon3 white autopsy-confirmed
      LOAD cases and normal controls. We further investigated the effect of the 523
      locus in its native genomic context using a luciferase expression system.
      RESULTS: The expression of both genes was significantly increased with disease.
      Mean expression of APOE and TOMM40 mRNA levels were higher in VL homozygotes
      compared with S homozygotes in the temporal and occipital cortexes from normal
      and LOAD cases. Results of a luciferase reporter system were consistent with the
      human brain mRNA analysis; the 523 VL poly-T resulted in significantly higher
      expression than the S poly-T. Although the effect of poly-T length on reporter
      expression was the same in HepG2 hepatoma and SH-SY5Y neuroblastoma cells, the
      magnitude of the effect was greater in the neuroblastoma than in the hepatoma
      cells, which implies tissue-specific modulation of the 523 poly-T. CONCLUSIONS:
      These results suggest that the 523 locus may contribute to LOAD susceptibility by
      modulating the expression of TOMM40 and/or APOE transcription.

PMID- 24439170
TI  - CASE 9--2014: Supracarinal tracheal tear after atraumatic endotracheal
      intubation: anesthetic considerations for surgical repair.

PMID- 24439178
TI  - [Problems and solutions in clinical practice in nonradiographic axial
      spondyloarthritis].

PMID- 24439171
TI  - Fondaparinux as a safe alternative for managing heparin-induced thrombocytopenia
      in postoperative cardiac surgery patients.
AB  - OBJECTIVE: Heparin-induced thrombocytopenia (HIT) is a rare but severe
      prothrombotic disorder of heparin treatment that leads to a decline in platelet
      count and thrombotic complications. If HIT is suspected, then heparin should be
      stopped and an alternative anticoagulant started. Fondaparinux is a factor Xa
      inhibitor that is not FDA-approved for this condition, but preliminary experience
      in HIT patients has been reported in the literature. The present study describes
      an experience of anticoagulation management with fondaparinux in postoperative
      cardiac surgery patients. DESIGN: Retrospective study. SETTING: Tertiary
      hospital. PARTICIPANTS: Patients who had undergone cardiac surgery from October
      2009 to June 2012. INTERVENTIONS: After HIT was suspected clinically, PaGIA and
      ELISA test were performed in all patients to diagnose HIT. In the patients
      included, anticoagulation was managed with a low dose of fondaparinux and daily
      monitoring of platelet count and anti-Xa level. MEASUREMENTS AND MAIN RESULTS: Of
      a total of 1,338 postoperative cardiac surgery patients, 15 patients were
      included (1.1%). Twelve of the 15 patients with HIT presented with renal failure
      and were under continuous renal replacement therapy. Two major bleeding events
      occurred during fondaparinux treatment, although platelet count and anti-Xa
      activity remained within the normal range. No thrombotic episodes were diagnosed.
      CONCLUSION: With daily monitoring of anti-Xa activity, fondaparinux appeared to
      be a good alternative to heparin in the study group; however, randomized clinical
      trials are needed to establish the safety and efficacy of this drug in critically
      ill, previously HIT patients.

PMID- 24439179
TI  - [Nonradiographic axial spondyloarthritis: early ankylosing spondylitis].

PMID- 24439180
TI  - [Attending the importance of bone health to patients with chronic obstructive
      pulmonary disease].

PMID- 24439181
TI  - [Some advice on prevention strategy of atherosclerosis].

PMID- 24439182
TI  - [Pay attentions to the clinical research and diagnostic strategy in multiple
      system atrophy].

PMID- 24439183
TI  - [The re-evaluation of 140 patients diagnosed as ankylosing spondylitis and
      nonradiographic axial spondyloarthritis].
AB  - OBJECTIVE: To re-evaluate the diagnoses of ankylosing spondylitis (AS) and
      nonradiographic axial spondyloarthritis (nr-axSpA) and analyze the incidence and
      reason of misdiagnosis. METHODS: Patients who were previously diagnosed as AS and
      nr-axSpA before referrals to Peking Union Medical College Hospital (PUMCH) were
      re-evaluated by three rheumatologists of PUMCH according to the modified New York
      criteria for AS and Assessment of SpondyloArthritis international Society (ASAS)
      axial SpA classification criteria for nr-axSpA. RESULTS: Totally 87 prior AS
      patients and 53 prior nr-axSpA patients were enrolled in this study. After re
      evaluation, 57 patients were still diagnosed as AS and 16 patients were still
      diagnosed as nr-axSpA. The misdiagnosis incidences were 34.48% and 69.81%,
      respectively. The misdiagnosis incidence of nr-axSpA was higher than that of AS
      (P < 0.01). CONCLUSIONS: The misdiagnosis of AS were mainly due to the
      misjudgment of sacroiliac joints by CT. The misdiagnosis of nr-axSpA were mainly
      due to the misjudgment of sacroiliac joints by magnetic resonance imaging.
      Moreover, the misuse of ASAS axial SpA classification criteria contributed to the
      misdiagnosis also.

PMID- 24439184
TI  - [A clinical analysis of 509 cases of sacroiliitis].
AB  - OBJECTIVE: To study the clinical features of sacroiliitis and differential
      diagnosis. METHODS: Totally 509 patients with chief complaints of back pain and
      diagnosed as sacroiliitis from January 2007 to January in Chinese PLA General
      Hospital were enrolled. The clinical manifestations, laboratory examinations,
      imaging and pathological data of the 509 patients were retrospectively analyzed.
      RESULTS: There were totally 406 male patients and 103 female patients. Among all
      509 patients, 436 were diagnosed as ankylosing spondylitis (AS)/
      spondyloarthropathy (SpA) , including 385 men. Thirty-six cases were diagnosed as
      sclerosing osteitis. Ten cases were diagnosed as sacroiliac joint degeneration.
      Ten cases were diagnosed as pyogenic sacroiliitis or sacroiliac joint
      tuberculosis. Four cases were diagnosed as diffuse idiopathic bone hypertrophy.
      Four cases were diagnosed as palmoplantar pustulosis arthritis. Four cases were
      diagnosed as metabolic bone disease. One case was diagnosed as sacroiliac joint
      gout. Four cases were diagnosed as neoplastic disease. HLA-B27 positive rate was
      86.9% in AS/SpA. Erythrocyte sedimentation rate and C-reactive protein were
      increased mildly-to-moderately in AS/SpA patients. Erythrocyte sedimentation rate
      and C-reactive protein increased obviously in sacroiliac joint infection and
      tumor diseases. Imaging characteristics were sacroiliac joint bone destruction.
      Magnetic resonance imaging showed sacroiliac joint bone marrow edema, but range
      was not beyond anatomical structure in AS/SpA. CONCLUSIONS: Based on disease
      distribution of sacroiliitis, AS/SpA is predominant while non-ankylosing
      spondylitis is not uncommon. Differential diagnoses of sacroiliitis should be
      considered to avoid malpractice, especially in patients with negative HLA-B27.

PMID- 24439185
TI  - [Peptidyl arginine deiminase 4 participates in the pathogenesis of rheumatoid
      arthritis by influencing histone methylation].
AB  - OBJECTIVE: To explore the probable function of peptidyl arginine deiminase 4
      (PAD4) in rheumatoid arthritis(RA). METHODS: Real-time quantitative polymerase
      chain reaction (PCR) was used to determine the expression of PAD4 mRNA in
      peripheral blood mononucleated cells (PBMCs) from 60 RA patients and 40 healthy
      individuals. Asymmetric di-methylation of histone H3R17, symmetric di-methylation
      and mono-methylation of H4R3 were semi-quantified by Western blotting in 12
      patients with osteoarthritis (OA), 26 patients with RA and 10 healthy controls.
      RESULTS: PAD4 mRNA in RA was significantly higher than that in healthy
      controls[34.6(16.7, 70.8) vs 20.6(11.1, 51.8), P < 0.05]. The level of histone
      H3R17 asymmetric di-methylation in RA was significantly higher than that of OA or
      control groups (71.34 +/- 25.65 vs 37.18 +/- 18.62 vs 50.67 +/- 13.99, P < 0.01)
      , which was positively related to Tender joint count and Swollen joint count in
      28 joints (r = 0.418, P = 0.034;r = 0.402, P = 0.042). The level of histone H4R3
      symmetric di-methylation was similar in RA,OA and control groups (75.02 +/- 20.35
      vs 57.92 +/- 22.77 vs 68.37 +/- 17.57, P > 0.05) . The level of histone H4R3 mono
      methylation in RA patients was significantly lower than that of OA patients and
      healthy individuals (11.24 +/- 7.81 vs 32.77 +/- 30.77 vs 51.20 +/- 47.14, P <
      0.05). The level of histone H4R3 mono-methylation in RA patients was negatively
      correlated to PAD4 (r = -0.643, P < 0.01) . The level of histone H3R17 asymmetric
      di-methylation and H4R3 symmetric di-methylation was not associated with PAD4
      level in RA group (r = -0.185, P = 0.377; r = 0.198, P = 0.344). CONCLUSIONS: The
      level of histone H3R17 asymmetric di-methylation is significantly higher and the
      level of histone H4R3 mono-methylation is significantly lower in RA patients
      comparing with OA and control groups. Abnormality of histone methylation may be
      one of the mechanisms for the development of RA. PAD4 probably plays an important
      role in rheumatoid arthritis by influencing histone methylation.

PMID- 24439187
TI  - [A retrospective analysis of ectopic varices in gastrointestinal tract diagnosed
      by endoscopy].
AB  - OBJECTIVE: To understand the incidence, causes, clinical manifestations and
      treatment of ectopic varices (EV) in gastrointestinal (GI) tract. METHODS: GI
      endoscopic examinations were carried out in 99 783 patients from January 2004 to
      October 2012 in General Hospital of PLA. Sixty-four cases of ectopic varices in
      GI tract were discovered. The clinical manifestations of EV patients and
      treatment were analyzed retrospectively. The literatures of EV were reviewed.
      RESULTS: The prevalence of EV in GI was 0.06% (64/99 783) in all patients
      undergoing endoscopic examinations, including 5 in the gastric antrum, 37 in the
      duodenum, 2 in the colon, 17 in the rectum, 1 in terminal ileum as well as whole
      colorectum, and 2 in the anastomotic stomas. The causes of EV included portal
      hypertension with cirrhosis in 52 cases (42 of hepatitis as dominant, 5 of
      alcoholic, 3 of biliary). Twenty-five cases had past history of endoscopic
      sclerotherapy, tissue adhesive injection or band ligation.Extrahepatic portal
      vein obstruction was seen in 4 cases (1 with pancreatic cancer, gastric cardia
      after surgery, pancreatic cancer after surgery, small intestine after partial
      hepatectomy respectively) and 8 cases uncertain. Nine cases accepted endoscopic
      tissue adhesive injection (no post-operative hemorrhage occurred in 9 cases and
      EV disappeared in 3 cases). Endoscopic band ligation was performed only for one
      patient. CONCLUSIONS: EV in GI tract is a rare condition, which occurs commonly
      in duodenum, colon, and rectum. Portal hypertension is the most common cause.
      Gastrointestinal hemorrhage is the main clinical manifestation. EV should be
      considered in GI bleeding, with gastroesophageal varices hemorrhage excluded.
      Endoscopic adhesive injection is an effective way to treat EV.

PMID- 24439186
TI  - [The design and baseline characteristics of a phase III study to evaluate the
      efficacy and safety of alogliptin versus placebo in type 2 diabetes mellitus in
      Mainland China].
AB  - OBJECTIVE: To assess the design and the Mainland China subgroup baseline
      characteristics of the study to evaluate the efficacy and safety of alogliptin
      versus placebo in subjects with type 2 diabetes (T2DM) as monotherapy, add-on to
      metformin or add-on to pioglitazone. METHODS: This was a multi-center,
      randomized, double-blind, placebo-controlled, 16-week study comparing alogliptin
      (ALO, 25 mg, 1/d) versus placebo (PLA) as monotherapy (A), add-on to metformin
      (B) or add-on to pioglitazone +/- metformin (C). The T2DM subjects with
      glycosylated hemoglobin A1c(HbA1c) between 7% and 10% and aged between 18 years
      and 75 years were enrolled and randomized to the alogliptin group and the placebo
      group in 1: 1 ratio with 16 weeks treatment. All patients were followed up every
      4 weeks. The safety endpoints consisted of the incidence of hypoglycemia and
      other adverse events. RESULTS: A total of 491 patients were enrolled in the
      Mainland China subgroup of the study (181 in group A, 186 in group B and 124 in
      group C). In each treatment group, the baseline characteristics including age,
      gender, body mass index, diabetes duration, HbA1c, fasting plasma glucose, body
      weight, daily dosage of metformin and daily dosage of pioglitazone were all well
      balanced. CONCLUSION: The demographic data, medical history, glycemic profile and
      treatment regimen at baseline in Mainland China subgroup are well balanced. The
      result of this study will provide the clinical evidence for the use of alogliptin
      in Chinese T2DM patients.

PMID- 24439188
TI  - [The clinical, endoscopic and pathologic features of Crohn's disease in the
      differentiation from intestinal tuberculosis].
AB  - OBJECTIVE: To investigate the clinical, endoscopic and pathologic features in the
      differential diagnosis between Crohn's disease(CD) and intestinal tuberculosis
      (ITB). METHODS: The complete clinical data of 107 patients with CD and 69
      patients with ITB in our hospital from January 2011 to January 2012 were
      retrospectively analyzed. The diagnostic value of the clinical and endoscopic
      scoring system was evaluated. RESULTS: CD occurred mainly in male. The salient
      features of CD included long duration of disease high incidence of colectomy.
      Comparing with patients with ITB, patients with CD have more cases of diarrhea,
      hematochezia, abdominal mass, intestinal obstruction, intestinal hemorrhage,
      perianal lesions, and extraintestinal manifestations (all P < 0.05).It's more
      frequent to have positive results of anti-Saccharomyces cerevisiae antibody
      (ASCA), perinuclear antineutrophil cytoplasmic antibody (pANCA) and fecal occult
      blood in CD patients, as well as low albumin, high C-reactive protein ( CRP),
      elevated platelet count and hematocrit (P < 0.05 or P < 0.01). The salient
      features of ITB included low fever, night sweats, active parenteral tuberculosis,
      increased erythrocyte sedimentation rate (ESR), chest X-ray abnormalities, the
      positive PPD (purified protein derivatives tuberculin) and T-SPOT (P < 0.05 or P
      < 0.01). Based on the imaging, CD often involved the small intestine, such as the
      intestinal stricture and abdominal abscess (P < 0.05), while mesenteric
      lymphadenopathy was more common in ITB (P < 0.05). The endoscopic examination
      showed that some patterns of disease involvement such as fissure-shape ulcer
      [41.12% (44/107) vs 5.80% (4/69)], cobblestone sign[15.89% (17/107) vs 4.35%
      (3/69)], lesions over four segment [24.30% (26/107) vs 7.25% (5/69)], rectum
      involvement [17.76% (19/107) vs 5.80% (4/69)], ileocecal valve stenosis [21.50%
      (23/107) vs 8.70% (6/69)] and mucosal bridge[5.61% (6/107) vs 0(0/69)] were more
      frequent in CD patients than those in ITB patients(P < 0.01 or P < 0.05). However
      circular ulcers[37.68% (26/69) vs 9.35% (10/107)], rat-bite-like ulcers[24.64%
      (17/69) vs 12.15% (13/107)], persistent open ileocecal valves [39.13% (27/69) vs
      19.63% (21/107)], tuberous and polypoid lesions[36.23% (25/69) vs 20.56%
      (22/107), 37.68% (26/69) vs 22.43% (24/107)] were more common in ITB (P < 0.01 or
      P < 0.05). In terms of pathological findings, certain characteristic features
      such as transmural inflammation [5.61% (6/107) vs 0(0/69)], fissure-liked ulcers
      [14.02% (15/107) vs 4.35% (3/69)], non-caseous granulomas [5.61% (6/107) vs
      0(0/69)], lymphoid hyperplasia [16.82% (18/107) vs 5.80% (4/69)] and crypt
      abscess [9.35% (10/107) vs 1.45% (1/69)] were more common in CD than those in
      ITB(P < 0.05). According to the clinical and endoscopic scoring system, the
      positive diagnostic rate of CD was 50.47% (54/107) and of ITB was 66.67% (46/69)
      (P < 0.05) . CONCLUSIONS: The differential diagnosis between CD and ITB should be
      considered carefully based on clinical, endoscopic, pathological characteristics.
      The clinical and endoscopic scoring system may contribute to distinguish CD and
      ITB.

PMID- 24439189
TI  - [The derivation and validation of a prediction rule for differential diagnosis of
      thyroid nodules].
AB  - OBJECTIVE: To set up a prediction rule for the pro-operative differential
      diagnosis of thyroid nodules and evaluate its clinical value. METHODS: All
      patients of thyroid nodules underwent thyroid operations in Changzheng hospital
      from June, 1997 to July, 2012 were included in this study. They were randomly
      divided into the derivation cohort (2/3) and the validation cohort (1/3). A
      prediction rule was developed based on the logistic regression model and the
      scoring system was established in accordance with assigning of the value of each
      variable beta in the model. The prediction consistency, discriminatory power and
      diagnostic accuracy were conducted to evaluate the clinical value of the scoring
      system. RESULTS: A total of 13 980 patients were enrolled in the study with 9195
      in the derivation cohort and 4785 in the validation cohort. The prediction rule
      consisted of 18 variables, which were gender, clinical manifestations including
      fever, neck sore, neck mass, palpitation and sweating, serum level of thyroid
      stimulating hormone (TSH) , free triiodothyronine (FT3) , thyroid peroxidase
      antibody (TPOAb) , thyroglobulin antibody (TgAb) , thyroglobulin (Tg) ,
      calcitonin and carcinoembryonic antigen (CEA) , ultrasonography features
      including nodules number, location, size, boundaries and ethological patterns and
      the presence and patterns of lymph nodes. The model showed good calibration
      consistency (P = 0.437) and discrimination power (area under the receiver
      operating characteristic curve was 0.928) in the derivation cohort. The
      sensitivity, specificity, accuracy, positive predictive value, negative
      predictive value, positive likelihood ratio and negative likelihood ratio of the
      model were 89.3%, 81.5%, 83.2%, 56.8%, 96.6%, 4.83 and 0.13, respectively.
      CONCLUSION: The prediction rule and its scoring system established in the study
      are efficacious for the calibration and discrimination of thyroid nodules in
      Chinese population, which could be a useful tool for the pro-operative risk
      stratification.

PMID- 24439190
TI  - [The risk factors for abnormal ankle-brachial index in type 2 diabetic patients
      and clinical predictive value for diabetic foot].
AB  - OBJECTIVE: To investigate the prevalence of diabetic foot (DF) and the normal,
      high and low ankle brachial index (ABI) in type 2 diabetic patients and explore
      the risk factor for abnormal ABI and the clinical predictive value for DF.
      METHODS: A total of 2681 type 2 diabetic patients who visited our hospital
      between January, 2007 to December, 2009 were enrolled in the study. The clinical
      data were analyzed and the risk factors for abnormal ABI were determined by
      logistic regression analysis. RESULTS: ABI was normal (0.9-<1.3) in 2362 cases
      (88.1%), while below 0.9 in 277 cases (10.3%) and equal or over 1.3 in 42 cases
      (1.6%). The elderly patients ( >= 60 years) had a higher prevalence of low ABI
      than the non-elderly patients (20.41% vs. 4.10%, P < 0.01) . The prevalence of DF
      was 25.63%, 3.05%, 26.19% in ABI<0.9, 0.9-<1.3 and >= 1.3 groups, respectively,
      and the prevalence in groups ABI<0.9 and >= 1.3 was higher than that in group ABI
      0.9-<1.3. Similar U-shape distribution was observed in the prevalence of abnormal
      ABI and DF. ABI was negatively correlated with age, diabetes duration, uric acid
      (UA), 24 hours microalbuminuria, while positively correlated with body mass index
      (BMI), diastolic blood pressure, triacylglyceride, total cholesterol and
      glycosylated hemoglobin A1c(HbA1c). Abnormal ABI was independently correlated
      with age, diabetes duration, HbA1c, UA, 24 hours microalbuminuria, diabetic
      kidney disease, diabetic retinopathy, diabetic peripheral neuropathy and diabetic
      vascular diseases. CONCLUSION: The prevalence of abnormal ABI is higher in the
      elderly patients with type 2 diabetes. Abnormal ABI could be an early predictor
      for DF.

PMID- 24439191
TI  - [The prophylactic effect of ceftazidime on early bacterial infection after
      autologous peripheral blood stem cell transplantation: a prospective randomized
      controlled trial].
AB  - OBJECTIVE: To evaluate the efficacy and safety of prophylactic ceftazidime on
      early bacterial infection in APBSCT recipients during neutropenia. METHODS:
      APBSCT recipients were prospectively randomly assigned to intravenous ceftazidime
      treatment group and control group (no prophylaxis of antibiotics). The treatment
      started from the first day until resolution of neutropenia or the appearance of
      early bacterial infection. RESULTS: From March 2010 to January 2013, 70 APBSCT
      recipients were enrolled in the study with 36 in treatment and 34 in control
      group. Overall, 29(41.4%) patients developed early bacterial infection, among
      which, 9(25.0%) in the treatment group and 20(58.8%) in the control group (P =
      0.004). The median infection free survival (IFS) was not reached in the treatment
      group and was 8 days in the control group (P = 0.005). Despite whether patients
      received single high dose melphalan or other conditioning regimes, the early
      bacterial infection rate was lower in the treatment group than in the control
      group, and the median IFS was longer in the treatment group than that in the
      control group. The mean courses of antibiotic administration were (8.08 +/- 2.03)
      days and (3.68 +/- 3.56) days respectively in the treatment and control groups (P
      < 0.001). However, the duration of empirical carbapenems were (1.67 +/- 3.03)
      days and (3.68 +/- 3.56) days respectively (P = 0.013). There was no significant
      difference of antibiotics cost per patient between the two groups. Four patients
      in the treatment group had a transient elevated serum creatinine. Overall, no
      infection related mortality was observed in either group. CONCLUSIONS:
      Prophylaxis of intravenous ceftazidime for APBSCT recipients is effective in
      preventing early bacterial infection with an acceptable toxicity and cost
      profile. However, it doesn't have effect on infection related mortality.
      Therefore, our results do not support the use of antibiotic prophylaxis for
      patients undergoing APBSCT.

PMID- 24439192
TI  - [The effects of cytochrome P450 2C19 genetic polymorphism on clopidogrel
      resistance and recent prognosis of patients with acute coronary syndrome].
AB  - OBJECTIVE: To investigate the relationship between cytochrome P450 (CYP) 2C19
      genetic polymorphism and clopidogrel resistance(CR) in patients with acute
      coronary syndrome(ACS), and to assess the effects of genetic polymorphism at
      CYP2C19 (681G>A) on the prognosis of ACS patients. METHODS: A total of 462
      patients with ACS were enrolled and received loading dose clopidogrel(600 mg).
      The blood samples of patients were collected before and 24 hours after taking
      loading dose clopidogrel, then 5 umol/L ADP-induced platelet aggregation ratio
      (PAR) was examined. Difference of two PAR <= 10% was defined as CR. Genomic DNA
      of patients were extracted from whole blood samples according to standard
      protocols and the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method was used to genotype the single nucleotide
      polymorphism of the CYP2C19 681G>A. According to whether the gene CYP2C19 681A
      was carried, patients were divided into two groups: wild type group and non-wild
      type group. After PCI treatment, patients were followed up for 6 months and major
      cardiac adverse events (MACE) happened during follow-up periods were recorded.
      RESULTS: Totally 127 enrolled cases were finally defined as CR (27.5%) , the
      frequency of CYP2C19 681A in patients with CR was higher than that in patients
      without CR (46.9% vs 28.1%, P < 0.01) . The ratio of CR in wild type group were
      lower than non-wide type group (17.4% vs 36.1%, P < 0.01) . Binary logistic
      regression analysis indicated that gene CYP2C19 681A was a strong independent
      predictor for CR in patients with ACS (OR 3.642, P < 0.05). After 6 months of
      follow-up, Kaplan-Meier survival analysis showed patients of wild type group and
      non-wild type group had significantly different cumulative non-events survival
      rates (94.8% vs 89.6%, Log rank = 4.296, P = 0.038) . CONCLUSIONS: The genetic
      polymorphism of CYP2C19 was associated with CR in patients with ACS. The mutation
      of CYP2C19 gene increased the risk of MACE in ACS patients undergoing PCI
      treatments and affected the patients' prognosis.

PMID- 24439193
TI  - [An analysis of risk factors for postpartum cardiac events in pregnant women with
      heart disease].
AB  - OBJECTIVE: To investigate the risk factors for postpartum cardiac events in
      pregnant women with heart diseases and to provide prenatal counseling for them.
      METHODS: A retrospective analysis was made in cases of pregnant women with heart
      diseases admitted to the surgical intensive care unit (SICU) of Anzhen Hospital
      from May 2004 to May 2012. Data were used to identify univariate and multivariate
      predictors for postpartum cardiac events. RESULTS: A total of 190 patients ( >=
      20 weeks gestation) were enrolled in the study with 134 (70.5%) of congenital
      heart disease, 30(15.8%) of rheumatic heart disease, 10 (5.3%) of cardiomyopathy,
      2 (1.1%) of peripartum cardiomyopathy and 14 (7.4%) of hypertensive heart
      disease. Postpartum cardiac events were observed in 42 cases with the incidence
      of 22.1%. A total of 7 cases resulted in death with the mortality rate of 3.7%.
      Among them, 5 cases were dead of circulatory collapse and pulmonary hypertensive
      crisis postpartum, while the other 2 cases with secondary pulmonary infection
      were died of respiratory and circulatory collapse. The baseline parameters of New
      York Heart Academy(NYHA)>1, left ventricular ejection fraction(LVEF)<50%, use of
      cardiac drugs and pulmonary artery hypertension (PAH)>80 mm Hg(1 mm Hg = 0.133
      kPa) were the independent predictors for postpartum cardiac events by univariate
      and multivariate logistic regression analysis. CONCLUSIONS: The incidence of
      postpartum cardiac events is high in pregnant women with heart diseases.
      Pulmonary artery hypertension and heart failure are the main causes of death.

PMID- 24439194
TI  - [The association between vitamin D deficiency and diabetic nephropathy in type 2
      diabetic patients].
AB  - OBJECTIVE: To evaluate the association between vitamin D deficiency and diabetic
      nephropathy in type 2 diabetic patients. METHODS: A total of 594 patients with
      type 2 diabetes were enrolled from the inpatients of the Nanjing Medical
      University Affiliated Nanjing Hospital. Fasting serum lipid profile, 25
      hydroxycalciferol vitamin D and urinary albumin excretion rate were investigated.
      The relationship between nephropathy and vitamin D deficiency ( < 20 ug/L) or
      insufficiency (20-<30 ug/L) was analyzed. RESULTS: Nephropathy was found in 177
      subjects (29.8%) with albuminuria in 141 and proteinuria in 36 subjects. Vitamin
      D deficiency was found in 180 subjects and insufficiency in 157 subjects. The
      proportion of vitamin D deficiency was higher in the individuals with nephropathy
      than those without nephropathy (36.2% vs 27.8%, P < 0.05). The urinary albumin
      excretion rate was significantly higher in the patients with vitamin D deficiency
      than those with normal vitamin D concentration [(123.0 +/- 299.2) mg/24h vs (47.6
      +/- 97.1) mg/24h, P < 0.01]. The prevalence of nephropathy was higher in the
      patients with vitamin D deficiency than those with normal vitamin D concentration
      (35.6% vs 26.1%, P < 0.05), while the prevalence of proteinuria was higher in
      patients with vitamin D deficiency (12.2% vs 3.1%, P < 0.01). Logistic regression
      analysis demonstrated that vitamin D deficiency was associated with nephropathy
      (OR 1.57, 95%CI 1.04-2.37), even after the adjustment for age, gender,
      hypertension, dyslipidemia, smoking status, use of angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers (OR 1.78, 95%CI 1.12-2.81). The
      Vitamin D concentration was significantly negatively correlated with urinary
      albumin excretion rate (r = -1.783, P < 0.001). CONCLUSIONS: Type 2 diabetic
      patients have a high prevalence of vitamin D deficiency. Vitamin D deficiency is
      independently associated with diabetic nephropathy.

PMID- 24439195
TI  - Staphylococcus aureus metabolic response to changing environmental conditions - a
      metabolomics perspective.
AB  - Microorganisms preserve their metabolic function against a wide range of external
      perturbations including biotic or abiotic factors by utilizing cellular
      adaptations to maintain cell homeostasis. Functional genomics aims to detect such
      adaptive alterations on the level of transcriptome, proteome and metabolome to
      understand system wide changes and to identify interactions between the different
      levels of biochemical organization. Microbial metabolomics measures metabolites,
      the direct biochemical response to the environment, and is pivotal to the
      understanding of the variability and dynamics of bacterial cell metabolism.
      Metabolomics can measure many different types of compounds including primary
      metabolites, secondary metabolites, second messengers, quorum sensing compounds
      and others, which all contribute to the complex bacterial response to an
      environmental change. Recent data confirmed that many metabolic processes in
      pathogenic bacteria are linked to virulence and invasive capabilities.
      Deciphering bacterial metabolism in response to specific environmental conditions
      and in specific genetic backgrounds will help map the complex network between the
      metabolome and the other "-omes". Here, we will review a selection of case
      studies for the pathogenic Gram-positive bacterium Staphylococcus aureus and
      summarize the current state of metabolomics literature covering staphylococci
      metabolism under different physiological states. 

PMID- 24439196
TI  - Staphylococcus aureus genomics and the impact of horizontal gene transfer.
AB  - Whole genome sequencing and microarrays have revealed the population structure of
      Staphylococcus aureus, and identified epidemiological shifts, transmission
      routes, and adaptation of major clones. S. aureus genomes are highly diverse.
      This is partly due to a population structure of conserved lineages, each with
      unique combinations of genes encoding surface proteins, regulators, immune
      evasion and virulence pathways. Even more variable are the mobile genetic
      elements (MGE), which encode key proteins for antibiotic resistance, virulence
      and host-adaptation. MGEs can transfer at high frequency between isolates of the
      same lineage by horizontal gene transfer (HGT). There is increasing evidence that
      HGT is key to bacterial adaptation and success. Recent studies have shed light on
      new mechanisms of DNA transfer such as transformation, the identification of
      receptors for transduction, on integration of DNA pathways, mechanisms blocking
      transfer including CRISPR and new restriction systems, strategies for evasion of
      restriction barriers, as well as factors influencing MGE selection and stability.
      These studies have also lead to new tools enabling construction of genetically
      modified clinical S. aureus isolates. This review will focus on HGT mechanisms
      and their importance in shaping the evolution of new clones adapted to antibiotic
      resistance, healthcare, communities and livestock. 

PMID- 24439197
TI  - First case with Huntington's disease in The Gambia.

PMID- 24439198
TI  - Physical precipitating factors in functional movement disorders.
AB  - BACKGROUND: A traditional explanation for functional (psychogenic) neurological
      symptoms, including functional movement disorders (FMD), is that psychological
      stressors lead to unconsciously produced physical symptoms. However,
      psychological stressors can be identified in only a proportion of patients.
      Patients commonly reported a physical event at onset of functional symptoms. In
      this study, we aim to systematically describe physical events and surrounding
      circumstances which occur at the onset of FMD and discuss their potential role in
      generation of functional symptoms. METHODS: We recruited 50 consecutive patients
      from a specialized functional movement disorders clinic. Semi-structured
      interviews provided a retrospective account of the circumstances in the 3 months
      prior to onset of the FMD. Questionnaires to assess mood disturbance and life
      events were also completed. RESULTS: Eleven males and 39 females were recruited.
      Forty (80%) patients reported a physical event shortly preceding the onset of the
      FMD. The FMD occurred after an injury in 11 patients and after an infection in 9.
      Neurological disorders (n=8), pain (n=4), drug reactions (n=3), surgery (n=3) and
      vasovagal syncope (n=2) also preceded the onset of the functional motor symptom.
      38% of patients fulfilled criteria for a panic attack in association with the
      physical event. CONCLUSIONS: In our cohort, physical events precede the onset of
      functional symptoms in most patients with FMD. Although historically neglected in
      favour of pure psychological explanation, they may play an important role in
      symptoms development by providing initial sensory data, which along with
      psychological factors such as panic, might drive subsequent FMD.

PMID- 24439199
TI  - Characteristics of anxiety and psychological well-being in chronic post-stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Anxiety and depression are common psychological
      conditions in post-stroke patients. In the present study, their relation with
      perceived quality of life and psychophysical well-being was investigated.
      METHODS: In the present cross-sectional study, chronic post-stroke patients
      (n=81; average years from stroke=4 +/- 4.6) were assessed with the Hospital
      Anxiety and Depression Scale (HADS), the 36-item Short-Form Healthy Survey (SF
      36) and the Psychological General Well-Being Index (PGWBI), as well as a brief
      neuropsychological assessment focused on the thinking ability and executive
      functions. RESULTS: Higher levels of anxiety compared to depressive symptoms were
      found. Hierarchical multiple regressions indicated that SF-36 predicts neither
      anxiety nor depression, and PGWBI subscales only partially. CONCLUSION: Post
      stroke anxiety can be a largely observed psychological distress in chronic
      patients: this pattern would be interpreted in relation to patients' expectations
      about their health status during a rehabilitation follow-up. SF-36 and PGWBI
      questionnaires did not provide satisfactory and reliable indexes: the relation
      between anxiety and both quality of life and psychological well-being needs
      further exploration.

PMID- 24439200
TI  - Multiple sclerosis is associated with psoriasis. A case-control study.
AB  - BACKGROUND: MS and psoriasis are both autoimmune diseases putatively mediated
      mainly by T cells. OBJECTIVE: We conducted a case control study to investigate
      whether patients with MS have a high rate of comorbid psoriasis. METHODS: The
      cohort consisted of 214 consecutive MS patients and a control group of 192
      consecutive patients with headache. RESULTS: There was a higher than expected
      frequency of psoriasis among the MS patients. There was no gender effect and none
      of the 9 affected MS patients were among the 22 MS patients with primary
      progressive disease. Six of those 9 patients started interferon-beta treatment
      after being diagnosed with MS, and 4 of them experienced exacerbation of
      psoriasis during exposure to interferon-beta. There was no exacerbation in the co
      morbid patients during treatment with other disease-modifying drugs. CONCLUSIONS:
      Our observation confirms other reports on an association of MS with autoimmune
      diseases and supports the hypothesis of autoimmune pathogenesis for MS. The
      current findings should raise the level of awareness of psoriasis among patients
      with MS, and of the need to consider a potential exacerbation of psoriasis by
      interferon-beta therapy.

PMID- 24439201
TI  - [Staphylococcus lugdunensis necrotizing fasciitis after abdominal dermolipectomy:
      report of two cases and review of the literature].
AB  - Necrotizing dermohypodermitis is a severe and potential fatal infection of soft
      tissues. We report two cases of 39- and 41-year-old patients operated of
      abdominal dermolipectomy and liposculpture after bariatric surgery. Because of a
      body mass index (BMI) less than 35kg/m(2), and trouble of interpretation of the
      SFAR recommendations, we have not achieved antibiotics. These patients presented
      an abdominal necrotizing dermohypodermitis at Staphylococcus lugdunensis,
      requiring wide excision of necrosis in emergency. The suites have been favorable
      after surgical and medical care. Perineal proximity, skin and subcutaneous
      peeling appear to be significant risk factors for this pathology. We suggest if
      case of abdominal dermolipectomy preventive measures in skin preparation and
      systematic antibiotics regardless of BMI. Indeed, the risk of a necrotizing
      dermohypodermitis recalls the importance of rigorous prevention and early
      diagnosis. 

PMID- 24439203
TI  - [Procedure adverse events: nursing care in central venous catheter fracture].
AB  - In a intensive care unit (ICU) there are many factors that can lead to the
      occurrence of adverse events. A high percentage of these events are associated
      with the administration of drugs. Diagnostic tests, such as computed tomography,
      is common in critically ill patients and technique can be performed with
      injection of contrast agent to enhance the visualization of soft tissue. The
      contrast is a medication and the nurse is responsible for its proper
      administration. The management of the critically ill patient is complex. ICU team
      and radiology shares responsibility for the care and safety of the patient safety
      during the transfer and performing tests with contrast. The World Health
      Organisation patient safety strategies, recommends analysing errors and learning
      from them. Therefore, it was decided to investigate the causes of the category E
      severity adverse events that occurred in a patient who was admitted to the ICU
      for septic shock of abdominal origin. An abdominal computed tomography was
      performed with contrast which was injected through a central venous catheter. The
      contrast did not appear in the image. What happened? Causal analysis helped to
      understand what triggered the event. A care plan and an algorithm were drafted to
      prevent it from happening again, with the following objectives: improving
      knowledge, skills and promoting positive attitudes towards patient safety,
      working at primary, secondary and tertiary care levels. 

PMID- 24439205
TI  - Chemical biology approaches to designing defined carbohydrate vaccines.
AB  - Carbohydrate antigens have shown promise as important targets for developing
      effective vaccines and pathogen detection strategies. Modifying purified
      microbial glycans through synthetic routes or completely synthesizing antigenic
      motifs are attractive options to advance carbohydrate vaccine development.
      However, limited knowledge on structure-property correlates hampers the discovery
      of immunoprotective carbohydrate epitopes. Recent advancements in tools for
      glycan modification, high-throughput screening of biological samples, and 3D
      structural analysis may facilitate antigen discovery process. This review focuses
      on advances that accelerate carbohydrate-based vaccine development and various
      technologies that are driving these efforts. Herein we provide a critical
      overview of approaches and resources available for rational design of better
      carbohydrate antigens. Structurally defined and fully synthetic oligosaccharides,
      designed based on molecular understanding of antigen-antibody interactions, offer
      a promising alternative for developing future carbohydrate vaccines. 

PMID- 24439204
TI  - The challenge and promise of glycomics.
AB  - Glycomics is a broad and emerging scientific discipline focused on defining the
      structures and functional roles of glycans in biological systems. The staggering
      complexity of the glycome, minimally defined as the repertoire of glycans
      expressed in a cell or organism, has resulted in many challenges that must be
      overcome; these are being addressed by new advances in mass spectrometry as well
      as by the expansion of genetic and cell biology studies. Conversely, identifying
      the specific glycan recognition determinants of glycan-binding proteins by
      employing the new technology of glycan microarrays is providing insights into how
      glycans function in recognition and signaling within an organism and with
      microbes and pathogens. The promises of a more complete knowledge of glycomes are
      immense in that glycan modifications of intracellular and extracellular proteins
      have critical functions in almost all biological pathways. 

PMID- 24439207
TI  - [Infected aneurysm of a branch of the superior mesenteric artery].
AB  - Aneurysm of the superior mesenteric artery is a rare finding. The risk of rupture
      is difficult to predict and manage. We report the case of a young woman who
      developed an aneurysm of the superior mesenteric artery in a context of bacterial
      endocarditis. Surgical resection without revascularization was successful. 

PMID- 24439206
TI  - Chemical and chemoenzymatic synthesis of glycoproteins for deciphering functions.
AB  - Glycoproteins are an important class of biomolecules involved in a number of
      biological recognition processes. However, natural and recombinant glycoproteins
      are usually produced as mixtures of glycoforms that differ in the structures of
      the pendent glycans, which are difficult to separate in pure glycoforms. As a
      result, synthetic homogeneous glycopeptides and glycoproteins have become
      indispensable probes for detailed structural and functional studies. A number of
      elegant chemical and biological strategies have been developed for synthetic
      construction of tailor-made, full-size glycoproteins to address specific
      biological problems. In this review, we highlight recent advances in chemical and
      chemoenzymatic synthesis of homogeneous glycoproteins. Selected examples are
      given to demonstrate the applications of tailor-made, glycan-defined
      glycoproteins for deciphering glycosylation functions. 

PMID- 24439208
TI  - All-cause mortality in a population-based type 1 diabetes cohort in the U.S.
      Virgin Islands.
AB  - OBJECTIVE: Type 1 diabetes remains a significant source of premature mortality;
      however, its burden has not been assessed in the U.S. Virgin Islands (USVI). As
      such, the objective of this study was to estimate type 1 diabetes mortality in a
      population-based registry sample in the USVI. RESEARCH DESIGN AND METHODS: We
      report overall and 20-year mortality in the USVI Childhood (<19 years old)
      Diabetes Registry Cohort diagnosed 1979-2005. Recent data for non-Hispanic blacks
      from the Allegheny County, PA population-based type 1 diabetes registry were used
      to compare mortality in the USVI to the contiguous U.S. RESULTS: As of December
      31, 2010, the vital status of 94 of 103 total cases was confirmed (91.3%) with
      mean diabetes duration 16.8 +/- 7.0 years. No deaths were observed in the 2000
      2005 cohort. The overall mortality rates for those diagnosed 1979-1989 and 1990
      1999 were 1852 and 782 per 100,000 person-years, respectively. Overall cumulative
      survival for USVI was 98% (95% CI: 97-99) at 10 years, 92% (95% CI: 89-95) at 15
      years and 73% (95% CI: 66-80) at 20 years. The overall SMR for non-Hispanic
      blacks in the USVI was 5.8 (95% CI: 2.7-8.8). Overall mortality and cumulative
      survival for non-Hispanic blacks did not differ between the USVI and Allegheny
      County, PA. CONCLUSIONS: This study, as the first type 1 diabetes mortality
      follow-up in the USVI, confirmed previous findings of poor disease outcomes in
      racial/ethnic minorities with type 1 diabetes.

PMID- 24439209
TI  - Diabetes in South and Central America: an update.
AB  - The estimated population of the South and Central America (SACA) Region is 467.6
      million and 64% is in the age range of 20-79 years but the population pyramid and
      age distribution are changing. The average prevalence of diabetes in the Region
      is 8.0% and is expected to reach 9.8% by the year 2035. Prevalence is much lower
      in rural settings than in urban and the differences attributed to lifestyle
      changes may be a target for intervention. The indigenous population is a
      particularly vulnerable group needing special attention. On average, 24% of the
      adult cases with diabetes are undiagnosed but in some countries this is still as
      high as 50%. Health expenditure due to diabetes in the Region is around 9% of the
      global total. Inadequate glycemic control, defined as HbA1c >7%, is a strong
      predictor of chronic complications which increase resource use in the Region and
      less than half of the patients enrolled in diabetes care programmes are at
      target. Fifty percent or more of the adult population is overweight/obese and
      around one third of the adult population has metabolic syndrome using regional
      cutoffs for waist circumference. The number of people with IGT is almost equal to
      those with diabetes presenting an additional challenge for prevention. Children
      with type 1 diabetes represent only 0.2% of the total population with diabetes
      but the incidence may be increasing. In many places they have limited access to
      insulin, and even when available, it is not used appropriately. The available
      epidemiological data provide the background to act in developing national
      diabetes programmes which integrate diabetes care with cardiovascular prevention
      and promote diabetes prevention as well. 

PMID- 24439210
TI  - Neurodevelopmental and epilepsy outcome in children aged one to five years with
      infantile spasms--a North Indian cohort.
AB  - PURPOSE: The present study was planned as there is paucity of outcome data of
      children with infantile spasms, from India where profile of patients is different
      from the western world. Moreover, most previous studies have either not used
      strict inclusion criteria or standardized psychometric tests for developmental
      outcome. METHODS: Ninety-five children, aged one-to-five years under follow up
      for more than six months in Pediatric Neurology Clinic of a tertiary care
      hospital with the diagnosis of infantile spasm were enrolled in this cross
      sectional study if they had completed one or more years after the onset of
      spasms. The study period was January-December 2011. Neurodevelopment of each
      child was assessed using Development Profile 3 and Gross Motor Function
      Classification System. History regarding epilepsy frequency and control in the
      last one year was taken. RESULTS: Perinatal asphyxia was the commonest etiology
      in 43/95 children (45.2%). Favorable neurodevelopmental outcome was observed in
      8/95 patients. Favorable epilepsy outcome in 58/95 (61.1%) patients was
      associated with treatment lag<=3 months between apparent onset of spasms and
      institution of therapy {OR 2 (1.1-3.8)} and response to first line antiepileptic
      drug {5 (2.6-10)}. CONCLUSIONS: The commonest etiology was potentially
      preventable perinatal cause. Early appropriate treatment may have a favorable
      epilepsy outcome.

PMID- 24439211
TI  - Refractory status epilepticus treated with trigeminal nerve stimulation.
AB  - Refractory status epilepticus (RSE) is a neurologic emergency associated with
      significant morbidity and mortality. Alternative therapies are needed for
      patients who do not respond to more traditional therapies for RSE. We report on a
      patient with RSE treated with external trigeminal nerve stimulation (eTNS). On
      admission, the patient was experiencing consecutive focal dyscognitive seizures
      with secondary generalization without recovery in between. His seizures remained
      refractory to multiple therapies, including IV lorazepam, valproic acid,
      levetiracetam, phenobarbital, and midazolam. Although a burst suppression pattern
      was achieved with a continuous pentobarbital infusion, seizures returned
      following attempts to taper it. Given his beneficial response to eTNS during a
      previous clinical trial, eTNS was initiated. Four days after starting eTNS, the
      pentobarbital infusion was finally weaned, and his EEG revealed no further
      seizures. The patient's mental status improved and he was ultimately discharged
      with only moderately severe disability. Our case demonstrates that eTNS may have
      antiseizure effects in RSE. Given our patient's quick response, such benefit may
      have arisen from EEG-desynchronization. If confirmed in larger studies, eTNS
      could one day be considered along with other adjuvant treatments for RSE. 

PMID- 24439212
TI  - fNIRS-EEG study of focal interictal epileptiform discharges.
AB  - Functional near-infrared spectroscopy (fNIRS) acquired with
      electroencephalography (EEG) is a relatively new non-invasive neuroimaging
      technique with potential for long term monitoring of the epileptic brain.
      Simultaneous EEG-fNIRS recording allows the spatio-temporal reconstruction of the
      hemodynamic response in terms of the concentration changes in oxy-hemoglobin
      (HbO) and deoxy-hemoglobin (HbR) associated with recorded epileptic events such
      as interictal epileptic discharges (IEDs) or seizures. While most previous
      studies investigating fNIRS in epilepsy had limitations due to restricted spatial
      coverage and small sample sizes, this work includes a sufficiently large number
      of channels to provide an extensive bilateral coverage of the surface of the
      brain for a sample size of 40 patients with focal epilepsies. Topographic maps of
      significant activations due to each IED type were generated in four different
      views (dorsal, frontal, left and right) and were compared with the epileptic
      focus previously identified by an epileptologist. After excluding 5 patients due
      to the absence of IEDs and 6 more with mesial temporal foci too deep for fNIRS,
      we report that significant HbR (respectively HbO) concentration changes
      corresponding to IEDs were observed in 62% (resp. 38%) of patients with
      neocortical epilepsies. This HbR/HbO response was most significant in the
      epileptic focus region among all the activations in 28%/21% of patients. 

PMID- 24439213
TI  - Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role
      in cold intolerance.
AB  - One of the sensory complications of traumatic peripheral nerve injury is thermal
      intolerance, which manifests in humans mainly as cold intolerance. It has a major
      effect on the quality of life, and adequate therapy is not yet available. In
      order to better understand the pathophysiological background of thermal
      intolerance, we focus first on the various transient receptor potential (TRP)
      channels that are involved in temperature sensation, including their presence in
      peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP
      channels in cold and heat intolerance is described showing three different
      mechanisms that contribute to thermal intolerance in the skin: (a) an increased
      expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower
      activation threshold of TRP channels and (c) the sprouting of non-injured nerve
      fibres. Finally, the data that are available on the effects of TRP channel
      agonists and antagonists and their clinical use are discussed. In conclusion, TRP
      channels play a major role in temperature sensation and in cold and heat
      intolerance. Unfortunately, the available pharmaceutical agents that successfully
      target TRP channels and counteract thermal intolerance are still very limited.
      Yet, our focus should remain on TRP channels since it is difficult to imagine a
      reliable treatment for thermal intolerance that will not involve TRP channels. 

PMID- 24439214
TI  - In situ vein grafting for lymphatic supermicrosurgery.

PMID- 24439215
TI  - Quilting sutures, fibrin tissue adhesive or both in reducing the incidence of
      seroma in the latissimus dorsi flap donor site? An evidence-based analysis.

PMID- 24439216
TI  - Total intramuscular course of the dominant vascular pedicle to the TMG flap: a
      unilateral finding.

PMID- 24439217
TI  - A new way to pre-expand the thoracodorsal artery perforator flap: expansion under
      the muscle.

PMID- 24439218
TI  - Supervised machine learning-based classification of oral malodor based on the
      microbiota in saliva samples.
AB  - OBJECTIVE: This study presents an effective method of classifying oral malodor
      from oral microbiota in saliva by using a support vector machine (SVM), an
      artificial neural network (ANN), and a decision tree. This approach uses
      concentrations of methyl mercaptan in mouth air as an indicator of oral malodor,
      and peak areas of terminal restriction fragment (T-RF) length polymorphisms (T
      RFLPs) of the 16S rRNA gene as data for supervised machine-learning methods,
      without identifying specific species producing oral malodorous compounds.
      METHODS: 16S rRNA genes were amplified from saliva samples from 309 subjects, and
      T-RFLP analysis was carried out with the DNA fragments. T-RFLP analysis provides
      information on microbiota consisting of fragment lengths and peak areas
      corresponding to bacterial strains. The peak area is equivalent to the frequency
      of a specific fragment when one molecule is selected from terminal fragments.
      Another frequency is obtained by dividing the number of species-containing
      samples by the total number of samples. An SVM, an ANN, and a decision tree were
      trained based on these two frequencies in 308 samples and classified the presence
      or absence of methyl mercaptan in mouth air from the remaining subject. RESULTS:
      The proportion that trained SVM expressed as entropy achieved the highest
      classification accuracy, with a sensitivity of 51.1% and specificity of 95.0%.
      The ANN and decision tree provided lower classification accuracies, and only
      classification by the ANN was improved by weighting with entropy from the
      frequency of appearance in samples, which increased the accuracy to 81.9% with a
      sensitivity of 60.2% and a specificity of 90.5%. The decision tree showed low
      classification accuracy under all conditions. CONCLUSIONS: Using T-RF proportions
      and frequencies, models to classify the presence of methyl mercaptan, a volatile
      sulfur-containing compound that causes oral malodor, were developed. SVM
      classifiers successfully classified the presence of methyl mercaptan with high
      specificity, and this classification is expected to be useful for screening
      saliva for oral malodor before visits to specialist clinics. Classification by a
      SVM and an ANN does not require the identification of the oral microbiota species
      responsible for the malodor, and the ANN also does not require the proportions of
      T-RFs.

PMID- 24439219
TI  - Cribriform and fused glands are patterns of high-grade pulmonary adenocarcinoma.
AB  - The 2011 International Association for the Study of Lung Cancer, American
      Thoracic Society, and European Respiratory Society classification of pulmonary
      adenocarcinoma recognizes the prognostic significance of different histologic
      patterns but does not address the issue of tumor grade. We previously developed
      an objective and prognostic grading system for pulmonary adenocarcinomas that is
      based on associating patterns with their metastatic potential. The best
      prognostic stratification was achieved by summing the grades of the 2 most
      predominant patterns (histologic score). Here, we extend this work by evaluating
      the prognostic importance of variant patterns of adenocarcinoma, which are not
      recognized by the new International Association for the Study of Lung
      Cancer/American Thoracic Society/European Respiratory Society classification.
      Pathologic specimens from 249 resected stage I adenocarcinomas were reviewed. The
      proportions of standard and nonstandard patterns (cribriform and fused glands)
      were recorded for each case. The associations between the presence of standard
      and nonstandard patterns, tumor histologic score, and disease-free survival were
      evaluated. Cribriform and fused gland patterns were observed in 15% and 29% of
      tumors, respectively. These nonstandard patterns each composed 10% to 100% of the
      entire tumors but were the predominant pattern in only 5% and 7% of tumors,
      respectively. The presence of complex glandular patterns was associated with
      solid pattern (P < .001) and high histologic score (P < .0001). Disease-free
      survival for tumors with predominant complex glandular patterns was similar to
      that for high-grade tumors (P = .932) and was significantly worse than that for
      low- and intermediate-grade tumors (P = .0025). Complex glandular patterns have a
      significant prognostic value and should be considered patterns of high-grade
      adenocarcinoma. 

PMID- 24439220
TI  - The majority of metachronous CIN1 and CIN3 lesions are caused by different human
      papillomavirus genotypes, indicating that the presence of CIN1 seems not to
      determine the risk for subsequent detection of CIN3.
AB  - Cervical intraepithelial neoplasia (CIN) is historically viewed as a progressive
      biologic continuum leading to cervical cancer. However, it has been questioned
      whether CIN1 lesions ever progress. To this end, we evaluated the number of
      patients with a CIN3 and a previous CIN1 diagnosis. Subsequently, metachronous
      CIN1 and CIN3 lesions were reviewed and human papillomavirus (HPV) genotyping was
      performed to evaluate whether CIN1 lesions do progress. The medical records of
      1819 patients diagnosed with a CIN3 lesion were retrieved from the archives, and
      prior Pap smear surveillance was available for 1474 patients. Forty-four CIN3
      patients (3.0%) had a previous CIN1 lesion, and review of the biopsies confirmed
      43 out of 44 CIN3 lesions and 37 out of 44 CIN1 lesions (78%). Three cases were
      not available for analysis, and in another three cases the quality of the
      isolated DNA was insufficient for further analysis. Out of the 30 remaining
      patients, 19 patients had different HPV genotypes in their CIN1 and CIN3 lesion.
      The cytological diagnosis leading to the CIN1 biopsy showed high-grade squamous
      intraepithelial lesion in 11 out of 19 patients with a different HPV genotype in
      the metachronous CIN1 and CIN3 lesions. High-grade squamous intraepithelial
      lesion was detected in 7 out of 11 patients with the same HPV genotype. Our
      results show that CIN3 lesions are rarely preceded by a CIN1 lesion. The majority
      of metachronous CIN1 and CIN3 lesions are caused by different HPV genotypes,
      indicating that the presence of CIN1 seems not to determine the risk for
      subsequent detection of CIN3. 

PMID- 24439221
TI  - Serrated lesions of the appendix frequently harbor KRAS mutations and not BRAF
      mutations indicating a distinctly different serrated neoplastic pathway in the
      appendix.
AB  - Appendiceal serrated polyps often morphologically resemble their colorectal
      counterparts and most pathologists employ colorectal diagnostic terminology when
      evaluating appendiceal serrated lesions. We analyzed 132 appendiceal lesions for
      mutations in the RAS/RAF/MAPK pathway in an attempt to (1) determine the
      frequency of these mutations in appendiceal serrated lesions and (2) correlate
      the histopathologic features with molecular alterations. The study group of
      appendiceal serrated lesions (n = 46) was divided into a non-dysplastic group
      (28/46, subclassified as 7 hyperplastic polyps and 21 sessile serrated
      adenoma/polyps (SSA/P) using colorectal diagnostic terminology) and dysplastic
      group (18/46, subclassified as 9 SSA/Ps with cytological dysplasia, 7 traditional
      serrated adenomas, and 2 adenomas with prominent serrations). Appendiceal non
      serrated dysplastic lesions (n = 86) comprised the control group. Of the 123
      lesions analyzed, KRAS mutations were identified in 64 (52%) appendiceal lesions.
      No significant difference in the presence of KRAS mutations were identified
      between serrated non-dysplastic lesions (13/25, 52%), serrated dysplastic lesions
      (7/14, 50%) and the control group of non-serrated dysplastic lesions (44/84, 52%)
      (P = 1.0). Importantly, KRAS mutations were identified in lesions that were
      histologically identical to colorectal hyperplastic polyps (2/6, 33%), SSA/Ps
      (11/19, 58%), and SSA/Ps with cytological dysplasia (4/7, 57%). Of the 126
      lesions tested, BRAF V600E mutations were identified in only 5 (4%) appendiceal
      lesions. Our results indicate that serrated lesions of the appendix often harbor
      KRAS mutations rather than BRAF mutations and suggest that the serrated pathway
      in the appendix is likely different than in the colon and rectum. 

PMID- 24439222
TI  - Comparison of the Haas and the Oxford classifications for prediction of renal
      outcome in patients with IgA nephropathy.
AB  - Pathologic features can provide valuable information for determining prognosis in
      IgA nephropathy (IgAN). However, it is uncertain whether the Oxford
      classification, a new classification of IgAN, can predict renal outcome better
      than previous ones. We conducted a retrospective cohort study in 500 patients
      with biopsy-proven IgAN between January 2002 and December 2010 to compare the
      ability of the Haas and the Oxford classifications to predict renal outcome.
      Primary outcome was a doubling of the baseline serum creatinine concentration (D
      SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D
      SCr and end-stage renal disease, respectively. There were graded increases in the
      development of D-SCr in the higher Haas classes. In addition, the primary
      endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than
      those without such lesions. In multivariate Cox regression analyses, the Haas
      class V (HR, 12.19; P=.002) and the Oxford T1 (hazard ratio [HR], 6.68; P<.001)
      and T2 (HR, 12.16; P<.001) lesions were independently associated with an
      increased risk of reaching D-SCr. Harrell's C index of each multivariate model
      with the Haas and the Oxford classification was 0.867 (P=.015) and 0.881
      (P=.004), respectively. This was significantly higher than that of model with
      clinical factors only (C=0.819). However, there was no difference in C-statistics
      between the 2 models with the Haas and the Oxford classifications (P=.348). This
      study suggests that the Haas and the Oxford classifications are comparable in
      predicting progression of IgAN.

PMID- 24439223
TI  - Chromosome 7q31.1 deletion in myeloid neoplasms.
AB  - We studied monosomy and deletions of chromosome 7 in 208 patients with myeloid
      disorders; we found 39 patients (19%) with monosomy or deletion of chromosome 7:
      24 patients with chromosome 7 deletion and 15 with monosomy 7. In the 24 patients
      with chromosome 7 deletions, studied with copy-number variants, short-tandem
      repeats, microsatellites, single nucleotide polymorphisms, and deletion
      polymorphisms, the most common deleted region was 7q31.1 (20 patients). Deletion
      polymorphism studies performed in these 20 patients showed an interstitial
      deletion of at least 140 kilobase in 6 patients; the deletion spans between the
      genes forkhead box P2 and Myo D family inhibitor domain containing. Because both
      genes do not seem to be involved in leukogenesis, we suggest to look carefully
      into this deletion for the presence of tumor suppressor genes and microRNAs. 

PMID- 24439224
TI  - EphB2 promotes cervical cancer progression by inducing epithelial-mesenchymal
      transition.
AB  - EphB2, a receptor tyrosine kinase for ephrin ligands, is overexpressed in various
      cancers and plays an important role in tumor progression. However, the expression
      and functions of EphB2 in cervical cancer remain unknown. In this study, we
      performed immunohistochemistry in clinical cervical specimens and found that
      EphB2 was overexpressed in the cervical cancer specimens, and its expression
      correlated with cancer progression. The percentage of EphB2-positive cells
      increased gradually from 28% in the normal cervix to 40% in high-grade squamous
      intraepithelial lesions, and ultimately to 69.8% in squamous cell carcinomas (P <
      .05). We overexpressed EphB2 in HeLa cells and silenced EphB2 in cervical cancer
      (C33A) cells, which expressed low and high levels of EphB2, respectively.
      Exogenous EphB2 promoted cell migration, invasion, and an epithelial-mesenchymal
      transition (EMT) signature, which is a complex process that occurs during
      organogenesis and cancer metastasis, whereas EphB2 silencing had the opposite
      effect (P < .05). Furthermore, HeLa cells with exogenous EphB2 exhibited a stem
      cell-like state that promoted tumorsphere formation in vitro and exhibited
      tumorigenesis potential in vivo (P < .05), whereas EphB2 silencing in C33A cells
      inhibited these stem cell properties (P < .05). In addition, we investigated the
      intracellular signaling pathways in cervical cancer and found that R-Ras
      expression correlated positively with EphB2 in clinical samples, and its activity
      was regulated by EphB2 in cervical cancer. These findings demonstrate that EphB2
      plays an important role in cervical cancer progression by orchestrating an EMT
      program through R-Ras activation. 

PMID- 24439225
TI  - Evidence for a morphologically distinct and functionally robust cell type in the
      proximal tubules of human kidney.
AB  - Acute tubular necrosis (ATN), elicited by ischemia and/or toxicity, is a
      potentially life-threatening condition. Histologically, ATN corresponds to
      necrosis and detachment of renal tubular epithelial cells. However, the tubules
      possess a considerable regenerative capacity and may be restored. We have
      previously identified a scattered population of progenitor-like cells within the
      proximal tubules, sharing marker expression with the parietal epithelial cells of
      Bowman's capsule as well as with renal tubules regenerating after ATN. In the
      present analysis, we use transmission electron microscopy, immunoelectron
      microscopy and immunofluorescence of human kidney cortex to further explore these
      cells. We demonstrate that the cells are smaller and have drastically fewer
      mitochondria than the surrounding proximal tubule cells. They also display strong
      expression of several structural proteins such as vimentin, collagen-7A1 and the
      tight junction protein claudin-1. To functionally assess these cells, we also
      developed a novel human kidney explant model of ATN demonstrating that the cells
      are more resilient to injury than the surrounding proximal tubular cells. Taken
      together the results suggest a novel robust cell type with a contrasting
      biological role to that of the bulk of proximal tubular epithelium. 

PMID- 24439226
TI  - Immunohistochemical distinction between intrahepatic cholangiocarcinoma and
      pancreatic ductal adenocarcinoma.
AB  - Distinction between primary intrahepatic cholangiocarcinoma (ICC) and metastatic
      pancreatic ductal adenocarcinoma (PDA) on a liver biopsy is essentially
      impossible histologically but has important clinical implications. In this study,
      41 ICCs and 60 PDAs were immunohistochemically evaluated for the expression of
      S100P, pVHL, IMP3, maspin, MUC5AC, and CK17 proteins. The results showed pVHL
      expression in 29 (71%) ICCs but in only 3 (5%) PDAs. S100P, MUC5AC, and CK17 were
      frequently expressed in PDAs, seen in 57 (95%), 40 (67%), and 36 (60%) cases,
      respectively. In contrast, only 11 (27%), 5 (12%), and 5 (12%) ICC cases
      expressed these proteins. IMP3 was expressed in 37 (90%) ICC and 54 (90%) PDA
      cases with equal frequency. All 60 (100%) PDA and 30 (73%) ICC cases showed
      positive maspin immunoreactivity. A S100P-/pVHL+/MUC5AC-/CK17- staining pattern
      was essentially indicative of ICC, whereas the S100P+/pVHL-/MUC5AC+/CK17+ and
      S100P+/pVHL-/MUC5AC-/CK17+ staining patterns were suggestive of PDA. These
      observations demonstrate that S100P, pVHL, MUC5AC, and CK17 are a useful
      immunohistochemical panel that may help distinguish primary ICC from metastatic
      PDA. 

PMID- 24439227
TI  - NEDD9 overexpression is associated with the progression of and an unfavorable
      prognosis in epithelial ovarian cancer.
AB  - Neural precursor cell-expressed, developmentally down-regulated 9 (NEDD9), a
      scaffolding protein, has been identified as a prometastatic and poor prognostic
      gene in multiple malignant tumors. However, the potential role of the NEDD9
      protein in epithelial ovarian cancer (EOC) remains unclear. In the present study,
      we investigated the expression of NEDD9 and the correlation between NEDD9
      expression and prognosis in EOC. NEDD9 expression was detected in 129 archived
      EOC specimens by immunohistochemical staining and in 28 freshly frozen EOC
      specimens by Western blotting. The expression of NEDD9 was evaluated in ovarian
      cancer cell lines by Western blotting and immunofluorescence. The association
      between the expression of NEDD9 and prognosis was determined by survival
      analysis. Results suggested that NEDD9 was overexpressed in EOC specimens
      compared with noninvasive epithelial ovarian tumors and normal ovarian specimens.
      A high level of NEDD9 expression significantly correlated with advanced-stage
      tumors (International Federation of Gynecology and Obstetrics classes III-IV, P <
      .001), high-grade carcinoma (grades 2-3, P < .001), and suboptimal primary
      cytoreductive surgery (residual disease <1cm, P = .021). The expression level of
      NEDD9 varied in ovarian cancer cell lines. Multivariate analysis indicated that
      NEDD9 overexpression (P = .033), advanced stage (P < .001), and high-grade
      carcinoma (P = .01) were independent predictors of poor survival. In conclusion,
      NEDD9 is overexpressed and associated with an unfavorable prognosis in EOC. NEDD9
      overexpression is an independent factor of poor prognosis and may serve as a
      potential biomarker in EOC. 

PMID- 24439228
TI  - Morphologic and molecular subtype status of individual tumor foci in multiple
      breast carcinoma. A study of 155 cases with analysis of 463 tumor foci.
AB  - The aim of this study is to evaluate biomarker immunophenotypic heterogeneity
      between separate tumor foci of multiple breast carcinoma, its correlation with
      morphologic features and tumor grade, and its influence on the treatment. One
      hundred fifty-five invasive multiple breast carcinomas were retrospectively
      analyzed over a 6-year period (2007-2012), and the expression of estrogen (ER)
      and progesterone (PR) receptors, Ki-67 proliferative index, human epidermal
      growth factor receptor 2 expression, morphologic subtype, and tumor grading were
      analyzed in each tumor focus. We found mismatches in immunohistochemical features
      in 71 (53.78%) of 132 patients with similar histology and in 13 (56.52%) of 23
      cases with different histology. When analyzing mismatches in ER and PR statuses
      together, in 4 (23.52%) of 17 cases, one of the tumor foci was ER or PR positive,
      whereas the index tumor did not express either marker. The most numerous
      mismatches (45 cases; 29.03%) concerned the proliferative index; in 14 cases
      (9.03%), the additional focus had a higher index than did the main focus, and in
      9 of these cases, the additional focus displayed a histologic grade of 3.
      Mismatches in human epidermal growth factor receptor 2 status appeared in 25
      (16.12%) cases. The histologic type of the additional foci was different from the
      index tumor in 23 (14.83%) cases. Assessment of all tumor foci would have
      determined 19 (12.25%) cases to receive different adjuvant treatments compared
      with what would have been indicated if only the biological status of the largest
      primary tumor was assessed. We strongly recommend assessing and reporting each
      tumor focus independently. 

PMID- 24439229
TI  - Indolent peripheral T-cell lymphoma involving the gastrointestinal tract.
AB  - We describe an unusual case of indolent peripheral T-cell lymphoma with
      multifocal involvement of the gastrointestinal tract. The patient, a 42-year-old
      Asian man, has been followed up for more than 10 years without chemotherapy and
      multiple gastrointestinal biopsies showing similar findings. Histologically, the
      neoplasm expanded into the lamina propria and/or focally extended into the
      submucosa and was composed of small- to medium-sized lymphocytes with slightly
      irregular nuclear contours and clear cytoplasm and rare large lymphocytes. The
      tumor cells were positive for CD3, CD8, granzyme B, and TIA-1 (subset) and
      negative for CD5, CD56, and Epstein-Barr virus-encoded RNA. Molecular studies for
      T-cell receptor gamma and/or beta chain gene rearrangement demonstrated the same
      clone at different sites and times during the course of the disease. Rare cases
      of indolent peripheral T-cell lymphoma of the gastrointestinal tract have been
      previously described and need to be further characterized to avoid the use of
      aggressive chemotherapy. 

PMID- 24439230
TI  - TP53 mutations of intestinal metaplasia.

PMID- 24439231
TI  - TP53 mutations of intestinal metaplasia--reply.

PMID- 24439232
TI  - Reversed MUC1/EMA polarity in both mucinous and micropapillary breast carcinoma.

PMID- 24439233
TI  - Time to change the way we diagnose mucinous carcinomas of the breast.

PMID- 24439234
TI  - Reversed MUC1/EMA polarity in both mucinous and micropapillary breast carcinoma-
      reply.

PMID- 24439235
TI  - Time to change the way we diagnose mucinous carcinomas of breast--reply.

PMID- 24439236
TI  - Long walk to treatment for XDR tuberculosis in South Africa.

PMID- 24439237
TI  - Long-term outcomes of patients with extensively drug-resistant tuberculosis in
      South Africa: a cohort study.
AB  - BACKGROUND: Long-term treatment-related outcomes in patients with extensively
      drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of
      patients to address knowledge gaps. METHODS: Between March, 2008, and August,
      2012, we prospectively followed up a cohort of 107 patients from three provinces
      in South Africa, who had been diagnosed with XDR tuberculosis between August
      2002, and February, 2008. Available isolates from 56 patients were genotyped to
      establish strain type and used for extended susceptibility testing. FINDINGS: All
      patients were treated empirically as inpatients with a median of eight drugs (IQR
      six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to
      at least eight drugs, and resistance to an increasing number of drugs was
      associated with the Beijing genotype (p=0.01). After 24 months of follow-up, 17
      patients (16%) had a favourable outcome (ie, treatment cure or completion), 49
      (46%) had died, seven (7%) had defaulted (interruption of treatment for at least
      2 consecutive months), and 25 (23%) had failed treatment. At 60 months, 12
      patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had
      defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from
      hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%)
      had failed treatment. Median survival of patients who had failed treatment from
      time of discharge was 19.84 months (IQR 4.16-26.04). Clustering of cases and
      transmission within families containing a patient who had failed treatment and
      been discharged were shown with genotypic methods. Net sputum culture conversion
      occurred in 22 patients (21%) and median time to net culture conversion was 8.7
      months (IQR 5.6-26.4). Independent predictors of probability of net culture
      conversion were no history of multidrug-resistant tuberculosis (p=0.0007) and use
      of clofazamine (p=0.0069). Independent overall predictors of survival were net
      culture conversion (p<0.0001) and treatment with clofazamine (p=0.021).
      Antiretroviral therapy was also a predictor of survival in patients with HIV
      (p=0.003). INTERPRETATION: In South Africa, long-term outcomes in patients with
      XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long
      stay or palliative care facilities are scarce, substantial numbers of patients
      with XDR tuberculosis who have failed treatment and have positive sputum cultures
      are being discharged from hospital and are likely to transmit disease into the
      wider community. Testing of new combined regimens is needed urgently and policy
      makers should implement interventions to minimise disease spread by patients who
      fail treatment. FUNDING: European and Developing Countries Clinical Trials
      Partnership, South African National Research Foundation (SARChI), and the South
      African Medical Research Council.

PMID- 24439239
TI  - Anorexia nervosa in adolescents: challenges remain.

PMID- 24439238
TI  - Day-patient treatment after short inpatient care versus continued inpatient
      treatment in adolescents with anorexia nervosa (ANDI): a multicentre, randomised,
      open-label, non-inferiority trial.
AB  - BACKGROUND: In-patient treatment (IP) is the treatment setting of choice for
      moderately-to-severely ill adolescents with anorexia nervosa, but it is costly,
      and the risks of relapse and readmissions are high. Day patient treatment (DP) is
      less expensive and might avoid problems of relapse and readmission by easing the
      transition from hospital to home. We investigated the safety and efficacy of DP
      after short inpatient care compared with continued IP. METHODS: For this
      multicentre, randomised, open-label, non-inferiority trial, we enrolled female
      patients (aged 11-18 years) with anorexia nervosa from six centres in Germany.
      Patients were eligible if they had a body-mass index (BMI) below the tenth
      percentile and it was their first admission to hospital for anorexia nervosa. We
      used a computer-generated randomisation sequence to randomly assign patients to
      continued IP or DP after 3 weeks of inpatient care (1:1; stratified for age and
      BMI at admission). The treatment programme and treatment intensity in both study
      groups were identical. The primary outcome was the increase in BMI between the
      time of admission and a 12-month follow-up adjusted for age and duration of
      illness (non-inferiority margin of 0.75 kg/m(2)). Analysis was done by modified
      intention to treat. This trial is registered with the International Standard
      Randomised Controlled Trial Number Register, number ISRCTN67783402, and the
      Deutsches Register Klinischer Studien, number DRKS00000101. FINDINGS: Between Feb
      2, 2007, to April 27, 2010, we screened 660 patients for eligibility, 172 of whom
      we randomly allocated to treatment: 85 to IP and 87 to DP. DP was non-inferior to
      IP with respect to the primary outcome, BMI at the 12-month follow-up (mean
      difference 0.46 kg/m(2) in favour of DP (95% CI, -0.11 to 1.02; pnon
      inferiority<0.0001). The number of treatment-related serious adverse events was
      similar in both study groups (eight in the IP group, seven in the DP group).
      Three serious adverse events in the IP group and two in the DP group were related
      to suicidal ideation; one patient in the DP attempted suicide 3 months after she
      was discharged. INTERPRETATION: DP after short inpatient care in adolescent
      patients with non-chronic anorexia nervosa seems no less effective than IP for
      weight restoration and maintenance during the first year after admission. Thus,
      DP might be a safe and less costly alternative to IP. Our results justify the
      broad implementation of this approach. FUNDING: German Ministry for Education and
      Research.

PMID- 24439240
TI  - A comparative study of peripherally-inserted and Broviac catheter complications
      in home parenteral nutrition patients.
AB  - BACKGROUND & AIMS: Peripherally inserted central venous catheters (PICC) have
      become increasingly popular for medium to long-term parenteral nutrition (PN) but
      there is limited data on the complication rates in this sub-group. We aimed to
      compare the rates of complications associated with tunneled catheters (Broviac)
      and PICC in home PN (HPN) patients. METHODS: All adult patients in an HPN program
      with a new Broviac or new PICC between 2009 and 2011 were included in this
      prospective observational study. Complication rates were compared by using
      Poisson regression and Kaplan Meier survival curves were used to compare the
      first complications that occurred. RESULTS: 204 catheters (133 Broviac and 71
      PICC) were inserted in 196 adult patients. Mean follow-up from catheter
      insertions to their removal was 276 +/- 219 days for Broviac (n = 86) vs. 74 +/-
      140.70 days for PICC (n = 56); p < 0.001. Complications were similar between
      Broviac and PICC (91/133 vs. 26/71). Catheter infection rate was lower in PICC
      (1.87 vs. 1.05 per 1000 catheter-days; p = 0.01). Catheter obstruction rates were
      similar for both catheters. Only PICC experienced venous thrombosis (0.4/1000).
      The proportion of catheters removed was lower in the Broviac group than in the
      PICC group (62.4% vs. 78.8%; p = 0.01) but those removed for complications were
      not different (28.6.7%vs. 25.3%; p = 0.64). CONCLUSIONS: In HPN patients, overall
      complications were similar in both the PICC and the Broviac groups. However, the
      Broviac catheter could be associated with an increase in catheter infection.

PMID- 24439241
TI  - Association between circulating irisin levels and the promotion of insulin
      resistance during the weight maintenance period after a dietary weight-lowering
      program in obese patients.
AB  - OBJECTIVE: Weight regain is associated with the promotion of insulin resistance.
      The newly discovered myokine irisin, which was proposed to be involved in the
      management of insulin sensitivity, could play a role in this process. This study
      aimed to investigate the association between irisin and reduced insulin
      sensitivity induced by weight regain. MATERIALS/METHODS: Insulin sensitivity was
      evaluated according to the homeostasis model assessment of insulin resistance
      (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30%
      reduced energy expenditure) to lose weight and was re-evaluated four or six
      months after treatment. Irisin plasma levels, as well as the levels of leptin,
      adiponectin, ghrelin and TNF-alpha, were quantified in a sub-cohort (n=73) from
      the initially studied patients at baseline (T0), at the diet endpoint (T1) and
      after the follow-up period (T2). RESULTS: After a successful dietary intervention
      to lose weight, 50% of the patients who regained the lost weight during the
      follow-up period were categorized as insulin resistant (HOMA-IR>=2.5) compared
      with only 25% of patients who maintained the weight loss (p=0.018). Importantly,
      in addition to the well-studied hormones leptin and adiponectin, irisin plasma
      levels were statistically associated with several risk factors for insulin
      resistance. Indeed, the increased risk of insulin resistance during the follow-up
      period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039).
      CONCLUSIONS: Circulating irisin predicts the insulin resistance onset in
      association with weight regain. Therefore, irisin could be secreted as an
      adaptive response to counteract the deleterious effect of excess adiposity on
      glucose homeostasis.

PMID- 24439242
TI  - Multiple short bouts of exercise over 12-h period reduce glucose excursions more
      than an energy-matched single bout of exercise.
AB  - OBJECTIVE: Long, uninterrupted bouts of sedentary behavior are thought to
      negatively influence postprandial glucose and insulin concentrations. We examined
      the effects of a 1-h bout of morning exercise versus intermittent walking bouts
      of short duration on glucose excursions and insulin secretion over 12-h.
      MATERIALS/METHODS: Eleven young, obese individuals (18-35 years, BMI>30kg/m(2))
      with impaired glucose tolerance were studied on three 12-h study days: 1)
      sedentary behavior (SED); 2) sedentary behavior with 1-h morning exercise (EX) at
      60%-65% VO2peak; and 3) sedentary behavior with 12-hourly, 5-min intervals of
      exercise (INT) at 60%-65% VO2peak. Meals (1046kJ/meal) were provided every 2-h.
      Blood samples were collected every 10 min and measured for glucose, insulin, and
      c-peptide concentrations. RESULTS: Glucose iAUC (12-h) was attenuated in the INT
      and SED conditions compared to the EX condition (P<0.05). Glucose concentrations
      were higher in the EX compared to the SED condition for ~150min (20% of the study
      day), and comparison of the EX-INT study days revealed that glucose
      concentrations were greater for~240min (~1/3 of the 12-hday). In the SED
      condition, the 12-h insulin iAUC was ~15% higher (P<0.05) compared to the INT and
      EX conditions. Insulin production rate was found to increase ~20% with INT
      exercise vs. the SED and EX condition (P<0.05). CONCLUSIONS: Short, frequent
      periods of exercise attenuated glucose excursions and insulin concentrations in
      obese individuals to a greater degree than an equal amount of exercise performed
      continuously in the morning.

PMID- 24439243
TI  - Treatment of acute intermittent porphyria in the emergency department.

PMID- 24439244
TI  - Nothing changes, nobody cares: understanding the experience of emergency nurses
      physically or verbally assaulted while providing care.
AB  - INTRODUCTION: Workplace violence has been recognized as a violent crime that
      requires targeted responses from employers, law enforcement, and the community.
      According to data from the Bureau of Labor Statistics, the most common source of
      nonfatal injuries and illnesses requiring days away from work in the health care
      and social assistance industry was assault on the health care worker. What is not
      well understood are the precursors and sequelae of violence perpetrated against
      emergency nurses and other health care workers by patients and visitors. The
      purpose of this study was to better understand the experience of emergency nurses
      who have been physically or verbally assaulted while providing patient care in US
      emergency departments. METHODS: The study was conducted using a qualitative
      descriptive exploratory design. The sample consisted of 46 written narratives
      submitted by e-mail by emergency nurses describing the experience of violence
      while providing care at work. Narrative analysis and constant comparison were
      used to identify emerging themes in the narratives. RESULTS: "Environmental,"
      "personal," and "cue recognition" were identified as the themes. Overall, nurses
      believed that violence was endemic to their workplace and that both limited
      recognition of cues indicating a high-risk person or environment and a culture of
      acceptance of violence were barriers to mitigation. DISCUSSION: These findings
      are consistent with the extant literature but with an added contribution of
      clearly identifying an underlying cultural acceptance of violence in the
      emergency department, as well as a distinct lack of cue recognition, in this
      sample of emergency nurses.

PMID- 24439245
TI  - Efficacy of axillary nerve block in elbow arthroscopic surgery: a randomized
      trial.
AB  - BACKGROUND: The purpose of this study was to evaluate postoperative pain levels
      after arthroscopic elbow surgery under general anesthesia and to determine
      whether an axillary nerve block provides additional pain management benefits
      compared with a portal site injection of local anesthetic. METHODS: Thirty-six
      patients undergoing arthroscopic elbow surgery under general anesthesia were
      randomized to either a study group receiving axillary nerve block (Ax group) or a
      control group receiving portal site injections of local anesthetic (Lo group).
      During the first 48 hours after surgery, pain visual analog scale (VAS) scores (0
      100), total amount of oral analgesics required, and patient satisfaction were
      assessed. RESULTS: Among all 36 patients, mean pain VAS scores at rest were 37,
      18, and 9 for the first 12-hour period and at 24 and 48 hours after surgery,
      respectively. The mean pain VAS scores during physiotherapy were 47 and 33 at 24
      and 48 hours postoperatively, respectively. No intergroup differences were
      observed between the Ax and Lo groups at any time point after surgery (P value
      range, .41 to .87). The mean number of loxoprofen tablets required during the 48
      hour study period was 5.1 in the Ax group and 4.5 in the Lo group (P = .90). The
      Ax and Lo groups had mean overall patient satisfaction scores of 91 and 91,
      respectively (P = .98). CONCLUSIONS: Postoperative pain levels after arthroscopic
      elbow surgery could be well managed with oral analgesics and local anesthetic. An
      axillary nerve block was not found to provide any postoperative pain control
      benefits.

PMID- 24439246
TI  - Kinematic characteristics of the scapula and clavicle during military press
      exercise and shoulder flexion.
AB  - BACKGROUND: The military press is an exercise frequently prescribed for scapular
      and shoulder rehabilitation. Although this exercise has previously been analyzed
      by electromyography, its kinematic features remain poorly understood. In this
      study, we aimed to clarify these features of the military press and suggest
      relevant clinical applications. METHODS: Sixteen healthy men participated in this
      study. The participants performed the military press while holding 2 kg weights,
      as well as shoulder flexion with and without 2 kg weights, and an electromagnetic
      motion capture system was used to analyze the kinematic features of the scapula,
      clavicle, and humerus during these exercises. The motions of the scapula and
      clavicle were analyzed at 10 degrees  increments of shoulder flexion from 30
      degrees  to 120 degrees . RESULTS: The military press involved less scapular
      internal rotation, greater upward rotation, and greater posterior tilt than
      shoulder flexion with or without weights, especially in the starting to middle
      range of shoulder flexion. Greater clavicular retraction and elevation were also
      seen during the military press. DISCUSSION: The movements of the scapula and
      clavicle during the military press differ significantly from those during
      shoulder flexion with and without weights. The kinematic features of the military
      press, which involved less scapular internal rotation, greater upward rotation,
      and greater posterior tilt than did shoulder flexion, may make it a useful re
      education exercise (if pain allows) for patients with decreased scapular external
      rotation, upward rotation, and posterior tilting. The results of this study might
      provide a kinematic basis for the use of this widely performed shoulder exercise.

PMID- 24439247
TI  - Ultrasound dimensions of the rotator cuff in young healthy adults.
AB  - BACKGROUND: No studies have looked at the rotator cuff dimensions in the young
      healthy population using ultrasonography. Our aim is to define the ultrasound
      dimensions of the rotator cuff in the healthy young adult population and explore
      correlations with other patient characteristics. METHODS: Thirty male and 30
      female healthy volunteers (aged 18-40 years), with no shoulder problems,
      underwent ultrasound assessment of both shoulders by a musculoskeletal
      radiologist. The dimensions of the rotator cuff, deltoid, and biceps were
      measured in a standardized manner. RESULTS: A total of 120 shoulders were
      scanned. The mean maximum width of the supraspinatus footprint was 14.9 mm in men
      and 13.5 mm in women (P < .001). The mean thickness of the supraspinatus tendon
      was 4.9 mm in women and 5.6 mm in men. The mean thickness of the subscapularis
      was 4.4 in men and 3.8 mm in women and for the infraspinatus was 4.9 mm in men
      and 4.4 mm in women. There was no correlation between height, weight, biceps, or
      deltoid thickness with any tendon measurements. Apart from supraspinatus tendon
      thickness, the difference between dominant and nondominant shoulders in the same
      sex was not significant for any other tendon dimensions. CONCLUSION: This study
      has defined the dimensions of the rotator cuff in the young healthy adult, which
      has not been previously published. This is important for the documentation of
      normal ultrasound anatomy of the rotator cuff and also demonstrates that the
      asymptomatic contralateral shoulder can and should be used to estimate the
      expected dimensions.

PMID- 24439248
TI  - Biologic resurfacing of the glenoid with humeral head resurfacing for
      glenohumeral arthritis in the young patient.
AB  - BACKGROUND: Resurfacing of the glenoid with an interposition soft tissue graft in
      conjunction with humeral head arthroplasty has been proposed as an option to
      improve glenohumeral arthritis in young patients while avoiding the potential
      complications associated with total shoulder arthroplasty. There currently exist
      minimal outcomes data for this procedure, and the results have not been
      consistent. The purpose of this study was to report on the outcomes in our cohort
      of patients aged younger than 55 years. METHODS: A multicenter review of 16
      patients who had undergone humeral head arthroplasty with soft tissue
      interposition grafting of the glenoid was performed. All patients had a minimum
      follow-up time of 24 months, unless revision surgery was required because of
      failure of the procedure. RESULTS: At a mean follow-up of 60 months, the patients
      showed improvement in the visual analog scale score for pain from 8.1 to 5.8 (P <
      .05), and the American Shoulder and Elbow Surgeons score improved from 23.2 to
      57.7 (P < .05). Forward elevation improved from 128 degrees  to 134 degrees  (P =
      .33), and external rotation improved from 28 degrees  to 32 degrees  (P = .5).
      Internal rotation showed no improvement. Conversion to a total shoulder
      arthroplasty was performed in 7 patients (44%) at a mean of 36 months.
      CONCLUSIONS: The optimal management for the young patient with arthritis has not
      yet been established. Because of the limited improvement in patient outcomes and
      the relatively high revision rate, biologic resurfacing of the glenoid with
      humeral head resurfacing is no longer our primary treatment option for young
      patients and should be used with caution.

PMID- 24439249
TI  - Family history of a mood disorder indicates a more severe bipolar disorder.
AB  - BACKGROUND: In the clinical setting, patients with bipolar disorder (BD) are
      often asked about potential family history (FH) of mood disorders. The aim of the
      present study was to examine differences between BD patients with FH of a mood
      disorder, and those without, on clinical, personality and social functioning
      characteristics, as well as on the symptomatic course of the disorder. METHODS:
      Data was collected from the Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD). For this report, we included 2600 patients, 1963 of those
      reported having a first-degree family member with a mood disorder, and 637
      reported of no such FH. We investigated the impact of FH on socio-demographic,
      clinical, personality and quality of life variables, as well as on symptomatology
      during the first year of treatment. RESULTS: Patients reporting FH of a mood
      disorder had an earlier age at onset of depression/mania, more phases, rapid
      cycling and more suicide attempts. Across different assessments, patients with FH
      showed consistently elevated depressive symptoms, such as lower concentration and
      energy, higher suicidal ideation, as well as increased racing thoughts and
      distractibility within the manic spectrum of symptoms. Further, the FH group had
      lower quality of life, higher neuroticism and higher personality disorder scores
      compared to patients without FH. LIMITATIONS: Information on FH was obtained
      through the proband. CONCLUSIONS: Overall, BD patients reporting FH of a mood
      disorder showed a worse clinical profile upon presentation for treatment and a
      more symptomatic course of the disorder.

PMID- 24439250
TI  - Validation of the Italian version of interpersonal sensitivity measure (IPSM) in
      adolescents and young adults.
AB  - BACKGROUND: Interpersonal sensitivity is a personality trait that describes as
      excessive awareness of both the behaviour and feelings of others. High
      interpersonal sensitivity has been associated with the development and
      maintenance of mental health problems. This study aimed to examine whether the
      Italian version of the interpersonal sensitivity measure (IPSM) has good internal
      consistence and convergent validity. METHODS: Validity was established on a
      sample of 153 Italian adolescents and young adult help seekers for several
      psychological problems. These subjects were divided in two groups - depressive
      spectrum disorder group (n=42) and other diagnosis group (n=111) - according to
      Structured Clinical Interview (SCID-I) for DSM-IV and Kiddie-Sads-Present and
      Lifetime Version (K-SADS-PL). For convergent validity, we studied the correlation
      between total and each subscale IPSM scores and the General Symptoms (included
      depressive and dysphoric symptoms) of Prodromal Questionnaire. RESULTS: The
      internal consistency were adequate and comparable to the original Boyce and
      Parker study. The validity was good, as indicated by both the convergent validity
      analysis and the depressive spectrum disorder group and other diagnosis group
      comparison. LIMITATIONS: The absence of another scale measuring interpersonal
      sensitivity to assess the construct validity of IPSM; the clinical heterogeneity
      of the sample; the absence of test re-test reliability of the instrument.
      CONCLUSIONS: Analysis of the results of internal consistency and convergent
      validity of the IPSM indicates that this version translated into Italian is valid
      and reliable.

PMID- 24439251
TI  - Development of IgG antibodies to Exophiala dermatitidis is associated with
      inflammatory responses in patients with cystic fibrosis.
AB  - BACKGROUND: The clinical importance of airway colonisation by the fungus
      Exophiala dermatitidis in patients with cystic fibrosis (CF) is unclear. We have
      previously shown that E. dermatitidis frequently colonises the airways of
      patients with CF. The aims of the present study were to determine whether
      patients who are colonised by E. dermatitidis have detectable fungal antigens in
      the circulation, develop anti-fungal antibodies, and show signs of inflammation
      and impaired respiratory function. METHODS: We collected sputum and serum samples
      consecutively from 98 sputum-producing patients with CF aged more than 12 years.
      The serum samples were subjected to bacterial and fungal culturing and analyses
      for fungal antigens and inflammatory factors. RESULTS: E. dermatitidis was
      recovered from 17 (17%) patients, the same isolation rate as for Aspergillus
      fumigatus. There were no difference regarding the levels of beta-glucan in the
      sera from E. dermatitidis culture-positive and culture-negative patients with CF.
      Serological analysis revealed significantly higher levels of IgG antibodies to E.
      dermatitidis cell wall fragments in the E. dermatitidis culture-positive
      patients. Patients with higher level of E. dermatitidis IgG antibodies were more
      often colonised with non-tuberculous Mycobacteria, and less often with
      Staphylococcus aureus. The increased levels of IgG antibodies directed against E.
      dermatitidis were positively associated with higher white blood cell counts,
      increased erythrocyte sedimentation rate, pancreatic insufficiency, intravenous
      antibiotic treatment, and they were negatively associated with respiratory
      function (FEV1 % predicted). Overall, 4/17 Exophiala-positive patients were
      diagnosed as having symptomatic infection with E. dermatitidis and were treated
      with broad-spectrum azoles. CONCLUSION: E. dermatitidis triggers antibody
      production and may cause significant airway infection in patients with cystic
      fibrosis.

PMID- 24439252
TI  - Cystic fibrosis carrier screening attitudes and multiple hypothesis testing.

PMID- 24439254
TI  - [Standardization in diagnosis of gastrointestinal and pancreatic neuroendocrine
      neoplasms: the Chinese consensus].

PMID- 24439256
TI  - The contribution of cell blocks in the diagnosis of mediastinal masses and hilar
      adenopathy samples from echobronchoscopy.
AB  - BACKGROUND: Cell block material from puncture can be obtained with endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in many cases. The
      aim of this study was to analyse the value of additional information from cell
      blocks obtained with EBUS-TBNA samples from mediastinal and hilar lymph nodes and
      masses. METHODS: Review of pathology reports with a specific diagnosis obtained
      from EBUS-TBNA samples of mediastinal or hilar lesions, prospectively obtained
      over a two-year period. The generation of cell blocks from cytology needle
      samples, the contribution to morphological diagnosis, and the possible use of
      samples for immunohistochemistry were analysed. RESULTS: One hundred and twenty
      nine samples corresponding to 110 patients were reviewed. The diagnosis was lung
      cancer in 81% of cases, extrapulmonary carcinoma in 10%, sarcoidosis in 4%,
      lymphoma in 2.7%, and tuberculosis in 0.9%. Cell blocks could be obtained in 72%
      of cases. Immunohistochemistry studies on the cell blocks were significantly
      easier to perform than on conventional smears (52.6% vs. 14%, P<.0001). In
      4cases, the cell block provided an exclusive morphological diagnosis
      (3sarcoidosis and one metastasis from prostatic carcinoma) and in 3carcinomas,
      subtype and origin could be identified. Exclusive diagnoses from the cell block
      were significantly more frequent in benign disease than in malignant disease (25%
      vs 0.9%, P=.002). CONCLUSIONS: Cell blocks were obtained from 72% of EBUS-TBNA
      diagnostic procedures. The main contributions of cell blocks to pathology
      examinations were the possibility of carrying out immunohistochemical staining
      for the better classification of neoplasms, especially extrapulmonary metastatic
      tumours, and the improved diagnosis of benign lesions.

PMID- 24439255
TI  - Relation of clinical culture method to T-cell memory status and efficacy in
      xenograft models of adoptive immunotherapy.
AB  - BACKGROUND AIMS: Cytotoxic T lymphocytes modified with chimeric antigen receptors
      (CARs) for adoptive immunotherapy of hematologic malignancies are effective in
      pre-clinical models, and this efficacy has translated to success in several
      clinical trials. Many early trials were disappointing in large part because of
      the lack of proliferation and subsequent persistence of transferred cells. Recent
      investigations have pointed to the importance of delivering highly proliferative
      cells, whether of naive or early memory phenotypes. METHODS: We investigated the
      influence of two common cell culturing methods used in early trials and their
      relationship to T-cell phenotype and pre-clinical efficacy. RESULTS: We observed
      that stimulation with soluble anti-CD3 antibody OKT-3 and high-dose interleukin-2
      produces more effector memory-type T cells with shorter average telomeres when
      compared with cells generated with the use of CD3/CD28 beads. When used in
      xenograft models of leukemia, bead-stimulated cells proliferated earlier and to a
      higher degree than those generated with the use of OKT-3/IL2 and resulted in
      better disease control despite no difference in distribution or migration
      throughout the mouse. Inclusion of the known successful clinical 4-1BB endodomain
      in the CAR could not rescue the function of OKT-3/IL-2-cultured cells. T cells
      isolated from animals that survived long-term (>120 days) retained a central
      memory-like phenotype and demonstrated a memory response to a large re-challenge
      of CD19-positive leukemia. CONCLUSIONS: In summary, we confirm that cells with a
      younger phenotype or higher proliferative capacity perform better in pre-clinical
      models and that cell culturing influences cell phenotype seemingly independent of
      the 4-1BB endodomain in the CAR structure.

PMID- 24439257
TI  - The chemistry of tetrameric acids in petroleum.
AB  - This article reviews the properties of a novel class of molecules: the tetrameric
      acids. These molecules have brought a large interest in petroleum science since
      the discovery of the family of molecules named ARN in 2004. ARN, which is
      naturally present in oil, is responsible, by reaction with calcium ion, of the
      formation of calcium naphthenate deposits; organic deposits that cause
      irregularities in crude oil production and processing. In order to study the
      properties of ARN, a model tetrameric acid molecule mimicking some of its
      properties named BP-10 has been developed in 2008 by Nordgard and Sjoblom and has
      been extensively used since then. After presenting the experimental techniques
      used to study the tetrameric acids, this review describes in detail the
      structure, preparation, detection and the bulk and interfacial properties of
      tetrameric acids ARN and BP-10. Finally the prediction of the operational
      problems with calcium naphthenate precipitation in new fields is discussed. 

PMID- 24439258
TI  - Physical aspects of heterogeneities in multi-component lipid membranes.
AB  - Ever since the raft model for biomembranes has been proposed, the traditional
      view of biomembranes based on the fluid-mosaic model has been altered. In the
      raft model, dynamical heterogeneities in multi-component lipid bilayers play an
      essential role. Focusing on the lateral phase separation of biomembranes and
      vesicles, we review some of the most relevant research conducted over the last
      decade. We mainly refer to those experimental works that are based on physical
      chemistry approach, and to theoretical explanations given in terms of soft matter
      physics. In the first part, we describe the phase behavior and the conformation
      of multi-component lipid bilayers. After formulating the hydrodynamics of fluid
      membranes in the presence of the surrounding solvent, we discuss the domain
      growth-law and decay rate of concentration fluctuations. Finally, we review
      several attempts to describe membrane rafts as two-dimensional microemulsion. 

PMID- 24439259
TI  - High-dose vitamin C management in dapsone-induced methemoglobinemia.
AB  - Methylene blue is the first-choice treatment of methemoglobinemia, but it is not
      readily available in most Korean emergency departments because of an import
      suspension. An 84-year-old woman with dapsone-induced massive methemoglobinemia
      visited our emergency department for unclear mentality and cyanosis. Because
      methylene blue was not available, we intravenously administrated vitamin C (VC)
      for symptomatic methemoglobinemia, although VC is not a universally accepted
      treatment. Vitamin C (10 g intravenously) administered 6 hourly successfully
      treated the dapsone-induced methemoglobinemia and did not adversely affect renal
      functions. Thus,we recommend that if methylene blue is unavailable, 6 hourly
      intravenous administrations of 10 g of VC should be considered for dapsone
      induced methemoglobinemia.

PMID- 24439260
TI  - What doesn't kill you makes you stronger: the anti-inflammatory effect of
      neutrophil respiratory burst.
AB  - In this issue of Immunity, Campbell et al. (2014) demonstrate that hypoxia caused
      by the respiratory burst of infiltrating neutrophils activates hypoxia inducible
      factor (HIF) in epithelial cells and protects the mucosa cells in an experimental
      model of inflammatory bowel disease.

PMID- 24439261
TI  - Cardiac macrophages: how to mend a broken heart.
AB  - A study by Epelman et al. (2014) in this issue of Immunity demonstrates that
      diverse subpopulations of macrophages reside in the adult heart and can be
      maintained by multiple mechanisms involving both local proliferation and
      contributions from monocytes.

PMID- 24439262
TI  - Professional differences in antigen presentation to iNKT cells.
AB  - Invariant natural killer T cells are preactivated lymphocytes that react upon
      recognition of CD1d-antigen complexes. Accordingly, any type of CD1d-positive
      cell could behave as antigen-presenting cell (APC). In this issue of Immunity,
      Arora et al. (2014), report that professional APCs still make the difference.

PMID- 24439263
TI  - GPR109a: the missing link between microbiome and good health?
AB  - A complex partnership between the host and the vast intestinal microbial
      ecosystem serves numerous biological activities including nutrition, immunity,
      and barrier function. In this issue of Immunity, Singh et al. (2014) demonstrate
      that microbial-derived butyrate mediated its protective activity against
      inflammation and colorectal cancer through GPR109a signaling.

PMID- 24439264
TI  - Th17 cells at the crossroads of autoimmunity, inflammation, and atherosclerosis.
AB  - The connection between inflammation, autoimmunity, and atherosclerosis is long
      established. In this issue of Immunity, Lim et al. (2014) demonstrate that
      oxidized low-density lipoprotein is one of the key environmental factors driving
      the development of inflammatory T helper 17 cells in atherosclerosis.

PMID- 24439265
TI  - Immune responses to HCV and other hepatitis viruses.
AB  - Five human hepatitis viruses cause most of the acute and chronic liver disease
      worldwide. Over the past 25 years, hepatitis C virus (HCV) in particular has
      received much interest because of its ability to persist in most immunocompetent
      adults and because of the lack of a protective vaccine. Here we examine innate
      and adaptive immune responses to HCV infection. Although HCV activates an innate
      immune response, it employs an elaborate set of mechanisms to evade interferon
      (IFN)-based antiviral immunity. By comparing innate and adaptive immune responses
      to HCV with those to hepatitis A and B viruses, we suggest that prolonged innate
      immune activation by HCV impairs the development of successful adaptive immune
      responses. Comparative immunology provides insights into the maintenance of
      immune protection. We conclude by discussing prospects for an HCV vaccine and
      future research needs for the hepatitis viruses. 

PMID- 24439266
TI  - Signaling through the adaptor molecule MyD88 in CD4+ T cells is required to
      overcome suppression by regulatory T cells.
AB  - Innate immune recognition controls adaptive immune responses through multiple
      mechanisms. The MyD88 signaling adaptor operates in many cell types downstream of
      Toll-like receptors (TLRs) and interleukin-1 (IL-1) receptor family members. Cell
      type-specific functions of MyD88 signaling remain poorly characterized. Here, we
      have shown that the T cell-specific ablation of MyD88 in mice impairs not only T
      helper 17 (Th17) cell responses, but also Th1 cell responses. MyD88 relayed
      signals of TLR-induced IL-1, which became dispensable for Th1 cell responses in
      the absence of T regulatory (Treg) cells. Treg cell-specific ablation of MyD88
      had no effect, suggesting that IL-1 acts on naive CD4(+) T cells instead of Treg
      cells themselves. Together, these findings demonstrate that IL-1 renders naive
      CD4(+) T cells refractory to Treg cell-mediated suppression in order to allow
      their differentiation into Th1 cells. In addition, IL-1 was also important for
      the generation of functional CD4(+) memory T cells.

PMID- 24439268
TI  - Acute caloric restriction improves glomerular filtration rate in patients with
      morbid obesity and type 2 diabetes.
AB  - AIM: The role of caloric restriction in the improvement of renal function
      following bariatric surgery is still unclear; with some evidence showing that
      calorie restriction can reduce proteinuria. However, data on the impact of
      caloric restriction on renal function are still lacking. METHODS: Renal function,
      as measured by glomerular filtration rate (GFR), was evaluated in 14 patients
      with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease
      before and after a 7-day very low-calory diet (VLCD). RESULTS: After the VLCD,
      both GFR and overall glucose disposal (M value) significantly increased from 72.6
      +/- 3.8 mL/min/1.73 m(-2) BSA to 86.9 +/- 6.1 mL/min/1.73 m(-2) BSA (P=0.026) and
      from 979 +/- 107 MUmol/min(1)/m(2) BSA to 1205 +/- 94 MUmol/min(1)/m(2) BSA
      (P=0.008), respectively. A significant correlation was observed between the
      increase in GFR and the rise in M value (r=0.625, P=0.017). CONCLUSION: Our
      observation of improved renal function following acute caloric restriction before
      weight loss became relevant suggesting that calory restriction per se is able to
      affect renal function.

PMID- 24439269
TI  - Comparison of nucleic acid sequence-based amplification and loop-mediated
      isothermal amplification for diagnosis of human African trypanosomiasis.
AB  - Diagnosis of human African trypanosomiasis (HAT) using molecular tests should
      ideally achieve high sensitivity without compromising specificity. This study
      compared 2 simplified tests, nucleic acid sequence-based amplification (NASBA)
      combined with oligochromatography (OC) and loop-mediated isothermal amplification
      (LAMP), executed on 181 blood samples from 65 Trypanosoma brucei gambiense HAT
      patients, 86 controls, and 30 serological suspects from Uganda. Basing on the
      composite reference standard, the diagnostic sensitivity and specificity of NASBA
      were 93.9% (95% confidence interval [CI] = 84.9-98.3%) and 100% (95% CI = 94.9
      100%), respectively. The same parameters for LAMP were 76.9% (95% CI = 64.8
      86.5%) and 100% (95% CI = 91.6-100%), respectively. The level of agreement
      between LAMP and microscopy was good with a kappa (kappa) value of 79.2% (95% CI
      = 69.4-88.9%), while that of NASBA-OC/microscopy was very good (kappa value
      94.6%; 95% CI = 89.3-99.8%). The sensitivity of NASBA-OC was significantly higher
      than that of LAMP (Z = 2.723; P = 0.007). These tests have potential application
      to HAT surveillance. 

PMID- 24439267
TI  - Embryonic and adult-derived resident cardiac macrophages are maintained through
      distinct mechanisms at steady state and during inflammation.
AB  - Cardiac macrophages are crucial for tissue repair after cardiac injury but are
      not well characterized. Here we identify four populations of cardiac macrophages.
      At steady state, resident macrophages were primarily maintained through local
      proliferation. However, after macrophage depletion or during cardiac
      inflammation, Ly6c(hi) monocytes contributed to all four macrophage populations,
      whereas resident macrophages also expanded numerically through proliferation.
      Genetic fate mapping revealed that yolk-sac and fetal monocyte progenitors gave
      rise to the majority of cardiac macrophages, and the heart was among a minority
      of organs in which substantial numbers of yolk-sac macrophages persisted in
      adulthood. CCR2 expression and dependence distinguished cardiac macrophages of
      adult monocyte versus embryonic origin. Transcriptional and functional data
      revealed that monocyte-derived macrophages coordinate cardiac inflammation, while
      playing redundant but lesser roles in antigen sampling and efferocytosis. These
      data highlight the presence of multiple cardiac macrophage subsets, with
      different functions, origins, and strategies to regulate compartment size.

PMID- 24439270
TI  - Reliability and validity of the Calgary Depression Scale for Schizophrenia (CDSS)
      in youth at clinical high risk for psychosis.
AB  - Assessment of depression in individuals who are considered to be at clinical high
      risk (CHR) for psychosis is important as high rates of depression have been
      reported in CHR individuals. The Calgary Depression Scale (CDSS) is the most
      widely used scale for assessing depression in schizophrenia. It has excellent
      psychometric properties, internal consistency, inter-rater reliability,
      sensitivity, specificity, and discriminant and convergent validity. The aim of
      this study was to test the reliability and validity of the CDSS in a sample of
      youth at CHR for psychosis. Participants were assessed for depression, presence
      of axis 1 mood disorders, and prodromal symptoms using the CDSS, the Structured
      Clinical Interview for DSM-IV Disorders (SCID-1), and the Scale of Prodromal
      Symptoms (SOPS). The CDSS total score as well as all individual items, except
      "guilty ideas of reference," were significantly associated with the presence of a
      major depressive disorder. Significant correlations were observed between CDSS
      total score and the dysphoric mood item on the SOPS. There was some evidence of
      overlap between the CDSS and both attenuated positive symptoms and negative
      symptoms as assessed by the SOPS. It is concluded that CDSS is a reliable scale
      suitable for assessing depression in individuals considered to be at CHR for
      psychosis. 

PMID- 24439271
TI  - Differences in eotaxin serum levels patients with recent onset and in chronic
      stable schizophrenia: a clue for understanding accelerating aging profile.

PMID- 24439273
TI  - The current views of clinical oncology trainees.

PMID- 24439272
TI  - Pre-treatment haemoglobin and peripheral blood lymphocyte count as independent
      predictors of outcome in carcinoma of cervix.
AB  - AIMS: To evaluate pre-treatment haemoglobin and peripheral blood lymphocyte (PBL)
      counts as predictors of treatment outcome in cervix carcinoma treated with
      radical chemoradiation. MATERIALS AND METHODS: Pre-treatment PBL counts and
      haemoglobin concentrations were retrieved from full blood count examinations from
      111 patients who received concurrent chemoradiotherapy. Overall survival and
      relapse-free survival were obtained using the Kaplan-Meier method by ranking the
      data by median haemoglobin and PBL, singly and then in association. Their
      independence and significance as predictors of outcome were analysed using the
      Cox proportional hazard model. RESULTS: Survival rates were significantly higher
      in patients whose haemoglobin level or PBL counts were at or above the
      corresponding median value. At 5 years, rates of overall survival were 77% versus
      41% (P = 0.0003) and 75% versus 42% (P = 0.002), when dichotomised around median
      haemoglobin and PBL, respectively. In multivariate and univariate analyses, both
      PBL and haemoglobin were independent and significant predictors for risk of death
      and relapse. Their predictive power was dramatically enhanced when the data were
      stratified into four groups by associating patients with haemoglobin >= median or
      < median with those whose PBL was >= or < median. CONCLUSION: Baseline PBL and
      haemoglobin seem to be strong, independent predictors of treatment outcome in
      carcinoma of the cervix, particularly if patient response is ranked using the
      predictors simultaneously. The hypothesis needs to be tested and, if confirmed,
      the markers should be used in combination to identify those at greater risk of
      failure who may benefit from additional therapy, with further validation in
      prospective trials offering treatment modification.

PMID- 24439274
TI  - Training and acute oncology services.

PMID- 24439275
TI  - Acute Oncology Service and its Implications on Training: the Specialty Trainee's
      Perspective.

PMID- 24439276
TI  - "Stamp-off" to micropattern sparse, multicomponent features.
AB  - Spatially patterned subtractive de-inking, a process we term "stamp-off,"
      provides a simple method to generate sparse, multicomponent protein
      micropatterns. It has been applied to control cell adhesion, study adhesion
      biology, as well as to micropattern fragile surfaces. This technique can also
      readily be applied to study nanoscale interactions between cell membrane
      receptors and surface-immobilized ligands. It is based on conventional
      microcontact printing and as such requires the same reagents, including
      photolithographically defined masters, a spin-coater, poly(dimethyl siloxane)
      (PDMS), and conventional cell culture reagents such as glass coverslips and
      adhesive proteins. Stamp-off is conceptually simplified into three steps: (1)
      generation of an appropriate cell culture substrate, PDMS-coated glass, (2)
      micropatterning with stamp-off, and (3) cell deposition. After elaborating each
      of these three methods, we discuss limitations of the technique and its
      applications. 

PMID- 24439277
TI  - Poly(vinyl alcohol)-micropatterned surfaces for manipulation of mesenchymal stem
      cell functions.
AB  - Micropatterning is a useful method to study the effects of biological and
      physical cues on cell functions. Various micropatterning methods have been
      developed for investigation of cell-cell interaction and cell-material
      interaction. As one of the potent methods, poly(vinyl alcohol) (PVA)-based
      micropatterning has been used to array cells in a pre-designed manner for a long
      term cell culture. Cell population and single cell arrays can be formed in the
      micropatterned surfaces. The micropatterned surfaces have used to generate a
      gradient cell density, different degree of cell spreading, protrusion and cell
      cell interaction and different geometry to investigate their effects on the
      differentiation of bone marrow-derived mesenchymal stem cells. This chapter
      highlights the latest development of PVA-based micropatterning and its
      application for manipulation of stem cell functions. 

PMID- 24439278
TI  - Patterning of polymeric cell culture substrates.
AB  - The purpose of this chapter is to provide a summary of polymer patterning
      technologies for biological applications and detailed instructions for resist
      free deep ultraviolet (UV) patterning of poly(styrene). Photochemical
      modifications of this polymer yield unstable peroxides together with stable
      oxidized chemical groups. The altered physicochemical properties of the polymer
      surface influence protein adsorption and cell adhesion. HepG2 (human hepatoma
      cell line), fibroblasts (L929, murine fibroblast line), and other cell lines
      exhibit strong adhesion on areas of UV-irradiated polymer. Masked irradiations
      open a simple, fast (cell patterns are obtained within a few hours), and
      economical route to obtain chemically patterned cell culture substrates. The
      described protocol is advantageous compared to silane-based patterning techniques
      on glass or thiol-based patterning on gold because of the elimination of any
      chemical treatment and the small size of achieved structures. The protocol is
      compatible with common clean room technologies; however, even without access to a
      clean room, structured substrates can be produced. The described technique can be
      a useful tool for a variety of cell cultures used to study biological processes
      like intercellular communication and organogenesis and for applications like
      biosensing or tissue engineering. 

PMID- 24439279
TI  - Photopatterning with a printed transparency mask and a protein-friendly
      photoresist.
AB  - Microscope projection photolithography (MPP) based on a protein-friendly
      photoresist is a versatile tool for the fabrication of protein- and cell
      micropatterned surfaces. Photomasks containing various features can be
      economically produced by printing features on transparency films. Features in
      photomasks are projected by the objective lens of a microscope, resulting in a
      significant reduction of the feature size to as small as ~1 MUm, close to the
      practical limit of light-based microfabrication. A fluorescence microscope used
      in most biology labs can be used for the fabrication process with some
      modifications. Using such a microscope, multistep MPP can be readily performed
      with precise registration of each micropattern on transparency film masks. Here,
      we describe methods of the synthesis and characterization of a protein-friendly
      photoresist poly(2,2-dimethoxy nitrobenzyl methacrylate-r-methyl methacrylate-r
      poly(ethylene glycol) methacrylate) and the setups of fluorescence microscopes
      and the MPP procedures. In addition, we describe the protocols used in the
      micropatterning of multiple lymphocytes and the dynamic micropatterning of
      adherent cells.

PMID- 24439280
TI  - Plasma microcontact patterning (PMUCP): a technique for the precise control of
      surface patterning at small-scale.
AB  - Plasma microcontact patterning (PMUCP) is a simple, efficient, and cost-effective
      method for the precise patterning of molecules on surfaces. It combines the use
      of low-pressure plasma with an elastomeric 3D mask to spatially control the
      removal of molecules, such as proteins, from a surface. The entire PMUCP process
      is subdivided into three main steps: surface precoating, plasma micropatterning,
      and a surface postcoating step. Surfaces are first precoated with a molecular
      species and then placed in close contact with the 3D mask. This allows the
      formation of two distinct regions: an un-masked open-region which is accessible
      to the plasma, from which the surface layer is removed, and, a contact region
      which is physically protected from exposure to the plasma. In the final step, a
      second molecule is added to back-fill the pattern generated through plasma
      treatment. The PMUCP technique allows the patterning of virtually any organic
      molecules on different surface materials and geometries (e.g., flat, curved
      surfaces, and 3D microstructures). Moreover, it is a simple and robust procedure.
      The main advantages of this approach over traditional microcontact printing are
      twofold: The stability of molecule binding to plasma-treated surfaces, and the
      separation of the surface functionalization step from the actual micropatterning
      step, which enables the precise control of concentration and uniformity of
      patterned molecules. In conclusion, PMUCP is a simple way to generate surface
      patterns that are highly reproducible, stable and uniform, making it a useful
      method for many applications. 

PMID- 24439281
TI  - Patterning gradients.
AB  - Surface-chemical and -morphological gradients can be extremely useful in cell
      biological research as high-throughput screening tools-for example, exposing a
      given set of cells to many different surface conditions at once, under identical
      ambient conditions, in order to monitor cell behavior such as proliferation or
      specific gene expression. They can also be used to investigate the effects of
      gradients themselves on cell behavior, such as migration. A number of simple,
      reliable techniques for both chemical- and morphological-gradient fabrication
      have been developed in our laboratories and are described in detail in the
      following. 

PMID- 24439282
TI  - Laser-assisted adsorption by photobleaching.
AB  - This chapter presents a simple method to produce substrate-bound protein patterns
      of micrometer resolution. Our approach uses only low power visible lasers and
      commercially available reagents to obtain arbitrary patterns of wide
      concentration range. We provide useful and detailed information on how to
      assemble the experimental setup to create engineered cell culture substrates
      using laser scanning or widefield illumination modalities. A protocol that
      includes the biochemistry, the optics, and the computer programming needed to
      fabricate functional micropatterns of single and multiple components is explained
      for readers without experience in optical engineering. Finally, we introduce a
      novel widefield illumination scheme for fabricating large surface patterns as
      well as how to make simple patterns using a standard commercial confocal
      microscope. 

PMID- 24439283
TI  - Micropatterning with a liquid crystal display (LCD) projector.
AB  - Photolithography has been applied to biological applications such as cell and
      protein micropatterning and the fabrication of microfluidic channels. However,
      the preparation of photomasks for projecting micropattern lighting images is
      often time consuming and costly. Therefore, we have developed maskless
      photolithography devices by modifying the optics of commercially available liquid
      crystal display (LCD) projectors from extended to reduced projection. The
      developed second and third devices produce practically a centimeter-scale
      micropattern by dividing an original large mask pattern into several patterns,
      which are individually and synchronously exposed to substrates with a motorized
      XY-stage, applying them to cell micropatterning and polydimethylsiloxane (PDMS)
      microfluidic device production. The first part of this chapter describes the
      developments of the maskless photolithography devices. The second part describes
      the exposure control system with a motorized XY-stage. The third part describes
      the applications of devices to cell micropatterning. The last part describes the
      application of the devices to the fabrication of the PDMS microfluidic channel.
      Maskless photolithography with an LCD projector has a large advantage with no
      requirement for a photomask. In particular, the maskless photolithography devices
      show a greater power by optimizing the conditions of pattern size and shape. 

PMID- 24439284
TI  - Cell patterning by laser-assisted bioprinting.
AB  - The aim of tissue engineering is to produce functional three-dimensional (3D)
      tissue substitutes. Regarding native organ and tissue complexity, cell density
      and cell spatial 3D organization, which influence cell behavior and fate, are key
      parameters in tissue engineering. Laser-Assisted Bioprinting (LAB) allows one to
      print cells and liquid materials with a cell- or picoliter-level resolution.
      Thus, LAB seems to be an emerging and promising technology to fabricate tissue
      like structures that have the physiological functionality of their native
      counterparts. This technology has additional advantages such as automation,
      reproducibility, and high throughput. It makes LAB compatible with the
      (industrial) fabrication of 3D constructs of physiologically relevant sizes. Here
      we present exhaustively the numerous steps that allow printing of viable cells
      with a well-preserved micrometer pattern. To facilitate the understanding of the
      whole cell patterning experiment using LAB, it is discussed in two parts: (1)
      preprocessing: laser set-up, bio-ink cartridge and bio-paper preparation, and
      pattern design; and (2) processing: bio-ink printing on the bio-paper. 

PMID- 24439285
TI  - Stereomask lithography for multi-protein patterning.
AB  - The advances of biologically-friendly micropatterning technologies have benefited
      many areas of biological and medical research, including quantitative biochemical
      assay, point-of-care devices, biosensing and regenerative medicine. Conventional
      micropatterning techniques, for example, photolithography and soft lithography,
      have seen encouraging adaptation to creating biological micropatterns in the last
      decades. However, they still have not completely addressed the major needs of
      constructing multi-object biological microarrays with single-cell resolution
      without requiring cleanroom access. In this chapter, we present a novel versatile
      biological lithography technique to achieve integrated multi-object patterning
      with high feature resolution and high adaptability to various biomaterials,
      referred to as stereomask lithography (SML). A novel three-dimensional stereomask
      has been developed for successive patterning of multiple objects. The stereomask
      consists of both patterned through holes, which layout new micropatterns and non
      through recesses, which protect pre-existing features on the substrate.
      Furthermore, high-precision reversible alignment among multiple bio-objects is
      achieved by adopting a peg-in-hole design between the substrate and stereomasks.
      As demonstration, we have successfully used the SML technique to construct
      complex biological microenvironment with various bio-functional components at
      single-cell resolution. 

PMID- 24439286
TI  - Fabrication of multifaceted, micropatterned surfaces and image-guided patterning
      using laser scanning lithography.
AB  - This protocol describes the implementation of laser scanning lithography (LSL)
      for the fabrication of multifaceted, patterned surfaces and for image-guided
      patterning. This photothermal-based patterning technique allows for selective
      removal of desired regions of an alkanethiol self-assembled monolayer on a metal
      film through raster scanning a focused 532 nm laser using a commercially
      available laser scanning confocal microscope. Unlike traditional photolithography
      methods, this technique does not require the use of a physical master and instead
      utilizes digital "virtual masks" that can be modified "on the fly" allowing for
      quick pattern modifications. The process to create multifaceted, micropatterned
      surfaces, surfaces that display pattern arrays of multiple biomolecules with each
      molecule confined to its own array, is described in detail. The generation of
      pattern configurations from user-chosen images, image-guided LSL is also
      described. This protocol outlines LSL in four basic sections. The first section
      details substrate preparation and includes cleaning of glass coverslips, metal
      deposition, and alkanethiol functionalization. The second section describes two
      ways to define pattern configurations, the first through manual input of pattern
      coordinates and dimensions using Zeiss AIM software and the second via image
      guided pattern generation using a custom-written MATLAB script. The third section
      describes the details of the patterning procedure and postpatterning
      functionalization with an alkanethiol, protein, and both, and the fourth section
      covers cell seeding and culture. We end with a general discussion concerning the
      pitfalls of LSL and present potential improvements that can be made to the
      technique.

PMID- 24439287
TI  - Print-to-print: printer-enabled out-of-cleanroom multiobject microprinting
      method.
AB  - Micropatterning techniques have gained growing interests from a broad range of
      engineering and biology researches as it realizes the high-throughput and highly
      quantitative investigations on miniature biological objects (e.g., cells and
      bacteria) by spatially defined micropatterns. However, most of the existing
      techniques rely on expensive instruments or intensive cleanroom access which may
      not be easy to be utilized in a regular biological laboratory. Here, we present
      the detailed procedures of a simple versatile microprinting process, referred to
      as Print-to-Print (P2P), to form multiobject micropatterns for potential
      biological applications. Only a solid-phase printer and custom-made
      superhydrophobic (SH) films are utilized for the printing and no thermal or
      chemical treatment is involved during the entire printing process. Moreover, the
      noncontact nature of droplet transferring and printing steps can be highly
      advantageous for sensitive biological uses. By the P2P process, a minimal feature
      resolution of 229 +/- 17 MUm has been successfully achieved. What's more, this
      approach has been applied to form micropatterning on various commonly used
      substrates in biology as well as multiobject co-patterns. In addition, the SH
      substrates have also been demonstrated to be reusable.

PMID- 24439288
TI  - Soft/elastic nanopatterned biointerfaces in the service of cell biology.
AB  - Engineering of biomimetic interfaces has become a valuable tool for guiding
      cellular processes such as adhesion, spreading, motility, as well as
      proliferation, differentiation, and apoptosis. The interaction of cells with the
      extracellular matrix (ECM) or with other cells is involved in nearly every
      cellular response in vivo. Recent wide-ranging evidence shows that crosstalk
      between different environmental stimuli can have a tremendous impact on various
      cell functions. Therefore, the defined control of these stimuli in vitro can
      contribute to the understanding of the mechanisms underlying the ability of cells
      to perform "intelligent" missions like acquiring, processing, and responding to
      environmental information. This chapter summarizes recently developed
      nanopatterned biomimetic systems that allow independent control of different
      stimuli and illustrates their applications in cellular studies. Particular
      attention is devoted to nanopatterned 2D and 3D artificial ECM systems based on
      poly(ethylene glycol) materials. These allow independent control over the
      material elasticity and the nanoscale distribution of bioligands on the surface.
      In the case of engineering artificial cellular interfaces, additional attention
      has to be devoted to the critical functions of protein transport regulators,
      namely the cell membrane and the dynamic actin cytoskeleton; both are essential
      for the signaling activity of individual proteins and the entire cell. 

PMID- 24439289
TI  - Combinatorial screening of mesenchymal stem cell adhesion and differentiation
      using polymer pen lithography.
AB  - The extracellular matrix (ECM) is a complex, spatially inhomogeneous environment
      that is host to myriad cell-receptor interactions that promote changes in cell
      behavior. These biological systems can be probed and simulated with engineered
      surfaces, but doing so demands careful control over the arrangement of ligands.
      Here, we describe how such surfaces can be fabricated by utilizing polymer pen
      lithography (PPL), which is a cantilever-free scanning probe lithographic method
      that utilizes polymeric pen arrays to generate patterns over large areas. With
      the advent of PPL, fundamental questions in cell biology can be answered by
      recapitulating cell-ECM interactions to explore how these interactions lead to
      changes in cell behavior. Here, we describe an approach for the combinatorial
      screening of cell adhesion behavior to gain understanding of how ECM protein
      feature size dictates osteogenic differentiation of mesenchymal stem cells. The
      technique outlined here is generalizable to other biological systems and can be
      paired with quantitative analytical methods to probe important processes such as
      cell polarization, proliferation, signaling, and differentiation. 

PMID- 24439290
TI  - High fidelity nanopatterning of proteins onto well-defined surfaces through
      subtractive contact printing.
AB  - In the pursuit to develop enhanced technologies for cellular bioassays as well as
      understand single cell interactions with its underlying substrate, the field of
      biotechnology has extensively utilized lithographic techniques to spatially
      pattern proteins onto surfaces in user-defined geometries. Microcontact printing
      (MUCP) remains an incredibly useful patterning method due to its inexpensive
      nature, scalability, and the lack of considerable use of specialized clean room
      equipment. However, as new technologies emerge that necessitate various nano
      sized areas of deposited proteins, traditional MUCP methods may not be able to
      supply users with the needed resolution size. Recently, our group developed a
      modified "subtractive MUCP" method which still retains many of the benefits
      offered by conventional MUCP. Using this technique, we have been able to reach
      resolution sizes of fibronectin as small as 250 nm in largely spaced arrays for
      cell culture. In this communication, we present a detailed description of our
      subtractive MUCP procedure that expands on many of the little tips and tricks
      that together make this procedure an easy and effective method for controlling
      protein patterning.

PMID- 24439291
TI  - The use of microarrays and fluorescence in situ hybridization for the study of
      mechanotransduction from topography.
AB  - The combination of transcriptomic analysis and fluorescence in situ hybridization
      (FISH) provides a robust methodology to study genomic changes in different
      biological conditions. Microarrays allow a global study of gene expression in
      response to the conditions of interest, with comparison between control(s) and
      one or more test condition(s). The messenger RNA amplification step permits
      detection of even low abundance transcripts, a critical advantage for
      applications such as biomaterials research, where the starting material may be
      limited. Different types of microarrays are commercially available that allow the
      investigation of specific features, such as exon arrays, microRNA arrays, and
      gene arrays. Microarrays are available for different model organisms, but we use
      Affymetrix (r) HuGene (r) ST (Sense Target) arrays, a type of gene array for
      analysis of human samples. FISH involves fluorescent detection of probe DNA
      hybridized to an in situ chromosomal target that can be either whole chromosomes
      or chromosomal segments. The overall hybridization is similar to labeling with
      radioactive probes but the incorporation of fluorescent detection of the probe
      sequences allows for high sensitivity in a simple and quick assay. FISH can be
      applied to a variety of specimen types depending on the study of interest. In
      this chapter, we describe the methodologies of these two techniques and provide
      technical tips that should help overcome challenges in carrying them out. 

PMID- 24439292
TI  - Micropatterning. Preface.

PMID- 24439293
TI  - Characteristics and process outcomes of patients presenting to an Australian
      emergency department for mental health and non-mental health diagnoses.
AB  - OBJECTIVES: To describe and compare characteristics and process outcomes of
      patient presentations made to a public hospital emergency department (ED) for
      mental health (MH) and non-mental health (NMH) diagnoses. METHODS: This was a
      descriptive, retrospective cross-sectional study of patients who presented to an
      Australian hospital ED between September 2011 and September 2012. Demographic,
      clinical and outcomes data were extracted from the ED information system. MH
      presentations were compared to NMH presentations. RESULTS: Nearly 5% of the
      66,678 ED presentations were classified as MH. Compared to the NMH group, a lower
      proportion in the MH group were seen by a physician within the recommended time
      frame (39.1% vs. 42.1%, p<0.001); had a higher admission rate (36.6% vs. 20.1%,
      p<0.001); shorter ED Length of Stay (LoS) if admitted (369 vs. 490min, p<0.001)
      and longer ED LoS if not admitted (241 vs. 187min, p<0.001). CONCLUSION: Time
      constraints in the busy ED environment are a potential barrier to the delivery of
      care for all patients who have the right to timely access to health care.
      Targeted improvements at the front end of the ED system and output processes
      between ED, community and inpatient admission are recommended for this site.

PMID- 24439294
TI  - Expression profiles of fetal membrane nicotinamide adenine dinucleotide phosphate
      oxidases (NOX) 2 and 3 differentiates spontaneous preterm birth and pPROM
      pathophysiologies.
AB  - INTRODUCTION: Nicotinamide adenine dinucleotide phosphate oxidases (NOX 1-5) are
      enzymes that generate cellular reactive oxygen species (ROS) besides mitochondria
      and might be important ROS sources associated with pregnancy complications,
      particularly preterm premature rupture of membranes (pPROM), that has been
      related to ROS. OBJECTIVE: To characterize NOX enzymes expression in human fetal
      membranes. METHODS: Differential expression and localization of NOX isoforms in
      human fetal membranes collected from women with uncomplicated pregnancies at
      term, preterm birth (PTB) or pPROM and in vitro in normal term membranes
      maintained in an organ explant system stimulated with water-soluble cigarette
      smoke extract (wsCSE) were documented by real time PCR and immunohistochemistry.
      RESULTS: Fetal membranes from term deliveries, PTB and pPROM expressed NOX 2, 3
      and 4 mRNAs whereas NOX 1 and 5 were not detected. NOX 2 expression was 2.3-fold
      higher in PTB than pPROM (p = 0.005) whereas NOX 3 was 2.2-fold higher in pPROM
      compared to PTB (p = 0.04). NOX 2 and 3 expressions at term mimicked pPROM and
      PTB, respectively. No difference in NOX 4 expression was observed among the
      studied groups. NOX 2, 3 and 4 were localized to both amniotic and chorionic
      cells. Expression of NOX 2, 3 and 4 were not significant in wsCSE-stimulated
      membranes compared to untreated controls. DISCUSSION/CONCLUSIONS: NOX enzymes are
      present in the fetal membranes and are differentially expressed in PTB and pPROM.
      Absence of any changes in NOXs expression after wsCSE stimulation suggests ROS
      generation in the membranes does not always correlate with NOX expression.

PMID- 24439295
TI  - Gene therapy arrives at the macula.

PMID- 24439296
TI  - Common adolescent mental disorders: transition to adulthood.

PMID- 24439298
TI  - The prognosis of common mental disorders in adolescents: a 14-year prospective
      cohort study.
AB  - BACKGROUND: Most adults with common mental disorders report their first symptoms
      before 24 years of age. Although adolescent anxiety and depression are frequent,
      little clarity exists about which syndromes persist into adulthood or resolve
      before then. In this report, we aim to describe the patterns and predictors of
      persistence into adulthood. METHODS: We recruited a stratified, random sample of
      1943 adolescents from 44 secondary schools across the state of Victoria,
      Australia. Between August, 1992, and January, 2008, we assessed common mental
      disorder at five points in adolescence and three in young adulthood, commencing
      at a mean age of 15.5 years and ending at a mean age of 29.1 years. Adolescent
      disorders were defined on the Revised Clinical Interview Schedule (CIS-R) at five
      adolescent measurement points, with a primary cutoff score of 12 or higher
      representing a level at which a family doctor would be concerned. Secondary
      analyses addressed more severe disorders at a cutoff of 18 or higher. FINDINGS:
      236 of 821 (29%; 95% CI 25-32) male participants and 498 of 929 (54%; 51-57)
      female participants reported high symptoms on the CIS-R (>=12) at least once
      during adolescence. Almost 60% (434/734) went on to report a further episode as a
      young adult. However, for adolescents with one episode of less than 6 months
      duration, just over half had no further common mental health disorder as a young
      adult. Longer duration of mental health disorders in adolescence was the
      strongest predictor of clear-cut young adult disorder (odds ratio [OR] for
      persistent young adult disorder vs none 3.16, 95% CI 1.86-5.37). Girls (2.12,
      1.29-3.48) and adolescents with a background of parental separation or divorce
      (1.62, 1.03-2.53) also had a greater likelihood of having ongoing disorder into
      young adulthood than did those without such a background. Rates of adolescent
      onset disorder dropped sharply by the late 20s (0.57, 0.45-0.73), suggesting a
      further resolution for many patients whose symptoms had persisted into the early
      20s. INTERPRETATION: Episodes of adolescent mental disorder often precede mental
      disorders in young adults. However, many such disorders, especially when brief in
      duration, are limited to the teenage years, with further symptom remission common
      in the late 20s. The resolution of many adolescent disorders gives reason for
      optimism that interventions that shorten the duration of episodes could prevent
      much morbidity later in life. FUNDING: Australia's National Health and Medical
      Research Council.

PMID- 24439297
TI  - Retinal gene therapy in patients with choroideremia: initial findings from a
      phase 1/2 clinical trial.
AB  - BACKGROUND: Choroideremia is an X-linked recessive disease that leads to
      blindness due to mutations in the CHM gene, which encodes the Rab escort protein
      1 (REP1). We assessed the effects of retinal gene therapy with an adeno
      associated viral (AAV) vector encoding REP1 (AAV.REP1) in patients with this
      disease. METHODS: In a multicentre clinical trial, six male patients (aged 35-63
      years) with choroideremia were administered AAV.REP1 (0.6-1.0*10(10) genome
      particles, subfoveal injection). Visual function tests included best corrected
      visual acuity, microperimetry, and retinal sensitivity tests for comparison of
      baseline values with 6 months after surgery. This study is registered with
      ClinicalTrials.gov, number NCT01461213. FINDINGS: Despite undergoing retinal
      detachment, which normally reduces vision, two patients with advanced
      choroideremia who had low baseline best corrected visual acuity gained 21 letters
      and 11 letters (more than two and four lines of vision). Four other patients with
      near normal best corrected visual acuity at baseline recovered to within one to
      three letters. Mean gain in visual acuity overall was 3.8 letters (SE 4.1).
      Maximal sensitivity measured with dark-adapted microperimetry increased in the
      treated eyes from 23.0 dB (SE 1.1) at baseline to 25.3 dB (1.3) after treatment
      (increase 2.3 dB [95% CI 0.8-3.8]). In all patients, over the 6 months, the
      increase in retinal sensitivity in the treated eyes (mean 1.7 [SE 1.0]) was
      correlated with the vector dose administered per mm(2) of surviving retina
      (r=0.82, p=0.04). By contrast, small non-significant reductions (p>0.05) were
      noted in the control eyes in both maximal sensitivity (-0.8 dB [1.5]) and mean
      sensitivity (-1.6 dB [0.9]). One patient in whom the vector was not administered
      to the fovea re-established variable eccentric fixation that included the ectopic
      island of surviving retinal pigment epithelium that had been exposed to vector.
      INTERPRETATION: The initial results of this retinal gene therapy trial are
      consistent with improved rod and cone function that overcome any negative effects
      of retinal detachment. These findings lend support to further assessment of gene
      therapy in the treatment of choroideremia and other diseases, such as age-related
      macular degeneration, for which intervention should ideally be applied before the
      onset of retinal thinning. FUNDING: UK Department of Health and Wellcome Trust.

PMID- 24439299
TI  - The effect of community treatment orders on outcome as assessed by the Health of
      the Nation Outcome Scales.
AB  - Many studies of outpatient commitment have assessed effects on health service use
      rather than psychiatric symptomatology. We examined whether patients on one form
      of outpatient commitment, community treatment orders (CTOs), had better outcomes
      on the Health of the Nation Outcome Scales (HoNOS). Cases and controls from three
      linked Western Australian databases were matched on age, sex, diagnosis and time
      of hospital discharge. These databases cover the entire state (population=2.3
      million). We compared HoNOS scores of CTO cases and controls at baseline, six-,
      and twelve-month follow-up, using multivariate analyses to further control for
      confounders. We identified 1296 CTO cases between 2004 and 2009 along with the
      same number of controls matched on age, sex, discharge date and mental health
      diagnosis (total n=2592). HoNOS scores were available for 1433 (55%) of the
      patients who could have had these recorded at baseline (748 CTO cases and 685
      controls). There was no significant difference in HoNOS scores at six- and twelve
      month follow-up between CTO cases and controls after adjusting for potential
      confounders at each time-point. Although the study was limited by missing data,
      outpatient commitment in the form of CTOs may not result in better psychiatric
      outcomes as measured by the HoNOS. 

PMID- 24439300
TI  - The implications for the biological and sociodynamic causal explanations of
      attitudes toward alcohol-dependent patients.
AB  - This study tested whether sole neurobiological or sociodynamic explanations of
      alcohol dependence altered respondents' attitudes toward alcohol-dependent
      patients. We investigated the effect of information leaflets on 444 participants:
      one group received an information leaflet with a biological explanation of AD;
      the other received a leaflet with a sole sociodynamic explanation of AD. A third,
      control group did not receive any leaflet. Afterwards, all three groups completed
      a questionnaire regarding their attitudes toward ADPs and their opinions of the
      underlying causes of AD. We found a significant group difference with regard to
      participants' agreement with a neurobiological explanation of AD. Moreover,
      respondents in the neurobiological intervention group considered the
      characteristics of ADP to be significantly more positive than those in the
      sociodynamic group. Furthermore, they were significantly less likely to accept AD
      as a self-inflicted disease. Correlation analysis revealed associations between
      accepting the sociodynamic disease model and all of the stigmatization dimensions
      tested in our questionnaire. In summary, stigmatization toward ADP was closely
      associated with the agreement with sociodynamic origins of AD in this study. 

PMID- 24439301
TI  - Do we need new treatments for type 2 diabetes?
AB  - Diagnosis of type 2 diabetes mellitus encompasses multiple pathophysiological and
      clinical situations. Type 2 diabetes mellitus is characterized by a long and
      changing natural history. Personal circumstances and preferences also condition
      the actual effectiveness and safety of drugs used. In recent decades, modern
      drugs have markedly expanded and improved therapeutic options. However, their
      effectiveness remains limited in clinical practice. The main objective of
      decreasing macrovascular complications is not fully proven. Adverse events,
      especially hypoglycemia and weight gain, are still frequent and decrease
      treatment adherence. The constant loss of endogenous islet cell reserve is the
      main determinant of the need for intensified therapies. Current treatments have
      failed to improve long-term beta cell mass/function. It is desirable to move
      forward to obtain new drugs that offer solutions sustainable in the long term.
      These drugs should be able to fit the individual circumstances and preferences of
      patients with diabetes mellitus. 

PMID- 24439302
TI  - Resting state electroencephalogram oscillatory abnormalities in schizophrenia and
      psychotic bipolar patients and their relatives from the bipolar and schizophrenia
      network on intermediate phenotypes study.
AB  - BACKGROUND: Abnormal resting state electroencephalogram (EEG) oscillations are
      reported in schizophrenia (SZ) and bipolar disorder, illnesses with overlapping
      symptoms and genetic risk. However, less evidence exists on whether similar EEG
      spectral abnormalities are present in individuals with both disorders or whether
      these abnormalities are present in first-degree relatives, possibly representing
      genetic predisposition for these disorders. METHODS: Investigators examined 64
      channel resting state EEGs of 225 SZ probands and 201 first-degree relatives
      (SZR), 234 psychotic bipolar (PBP) probands and 231 first-degree relatives
      (PBPR), and 200 healthy control subjects. Eight independent resting state EEG
      spectral components and associated spatial weights were derived using group
      independent component analysis. Analysis of covariance was conducted on spatial
      weights to evaluate group differences. Relative risk estimates and familiality
      were evaluated on abnormal spectral profiles in probands and relatives. RESULTS:
      Both SZ and PBP probands exhibited increased delta, theta, and slow and fast
      alpha activity. Post-hoc pair-wise comparison revealed increased frontocentral
      slow beta activity in SZ and PBP probands as well as SZR and PBPR. Augmented
      frontal delta activity was exhibited by SZ probands and SZR, whereas PBP probands
      and PBPR showed augmented fast alpha activity. CONCLUSIONS: Both SZ and PBP
      probands demonstrated aberrant low-frequency activity. Slow beta activity was
      abnormal in SZ and PBP probands as well as SZR and PBPR perhaps indicating a
      common endophenotype for both disorders. Delta and fast alpha activity were
      unique endophenotypes for SZ and PBP probands, respectively. The EEG spectral
      activity exhibited moderate relative risk and heritability estimates, serving as
      intermediate phenotypes in future genetic studies for examining biological
      mechanisms underlying the pathogenesis of the two disorders.

PMID- 24439303
TI  - Three-week bright-light intervention has dose-related effects on threat-related
      corticolimbic reactivity and functional coupling.
AB  - BACKGROUND: Bright-light intervention is reported to successfully treat
      depression, in particular seasonal affective disorder, but the neural pathways
      and molecular mechanisms mediating its effects are unclear. An amygdala
      prefrontal cortex corticolimbic circuit regulates responses to salient
      environmental stimuli (e.g., threat) and may underlie these effects. Serotonin
      signaling modulates this circuit and is implicated in the pathophysiology of
      seasonal and other affective disorders. METHODS: We evaluated the effects of a
      bright-light intervention protocol on threat-related corticolimbic reactivity and
      functional coupling, assessed with an emotional faces functional magnetic
      resonance imaging paradigm at preintervention and postintervention. In a double
      blind study conducted in the winter, 30 healthy male subjects received bright
      light intervention (dose range between participants: .1-11.0 kilolux) for 30
      minutes daily over a period of 3 weeks. Additionally, we considered serotonin
      transporter-linked polymorphic region (5-HTTLPR) genotype status as a model for
      differences in serotonin signaling and moderator of intervention effects.
      RESULTS: Bright-light dose significantly negatively affected threat-related
      amygdala and prefrontal reactivity in a dose-dependent manner. Conversely,
      amygdala-prefrontal and intraprefrontal functional coupling increased
      significantly in a dose-dependent manner. Genotype status significantly moderated
      bright-light intervention effects on intraprefrontal functional coupling.
      CONCLUSIONS: This is the first study to evaluate the effects of clinically
      relevant bright-light intervention on threat-related brain function. We show that
      amygdala-prefrontal reactivity and communication are significantly affected by
      bright-light intervention, an effect partly moderated by genotype. These novel
      findings support that this threat-related corticolimbic circuit is sensitive to
      light intervention and may mediate the therapeutic effects of bright-light
      intervention.

PMID- 24439312
TI  - Adjuvant chemotherapy for local relapse breast cancer.

PMID- 24439304
TI  - Re-establishment of anxiety in stress-sensitized mice is caused by monocyte
      trafficking from the spleen to the brain.
AB  - BACKGROUND: Persistent anxiety-like symptoms may have an inflammatory-related
      pathophysiology. Our previous work using repeated social defeat (RSD) in mice
      showed that recruitment of peripheral myeloid cells to the brain is required for
      the development of anxiety. Here, we aimed to determine if 1) RSD promotes
      prolonged anxiety through redistribution of myeloid cells and 2) prior exposure
      to RSD sensitizes the neuroimmune axis to secondary subthreshold stress. METHODS:
      Mice were subjected to RSD and several immune and behavioral parameters were
      determined .5, 8, or 24 days later. In follow-up studies, control and RSD mice
      were subjected to subthreshold stress at 24 days. RESULTS: Repeated social defeat
      induced macrophage recruitment to the brain corresponded with development and
      maintenance of anxiety-like behavior 8 days after RSD, but neither remained at 24
      days. Nonetheless, social avoidance and an elevated neuroinflammatory profile
      were maintained at 24 days. Subthreshold social defeat in RSD-sensitized mice
      increased peripheral macrophage trafficking to the brain that promoted re
      establishment of anxiety. Moreover, subthreshold social defeat increased social
      avoidance in RSD-sensitized mice compared with naive mice. Stress-induced
      monocyte trafficking was linked to redistribution of myeloid progenitor cells in
      the spleen. Splenectomy before subthreshold stress attenuated macrophage
      recruitment to the brain and prevented anxiety-like behavior in RSD-sensitized
      mice. CONCLUSIONS: These data indicate that monocyte trafficking from the spleen
      to the brain contributes re-establishment of anxiety in stress-sensitized mice.
      These findings show that neuroinflammatory mechanisms promote mood disturbances
      following stress-sensitization and outline novel neuroimmune interactions that
      underlie recurring anxiety disorders such as posttraumatic stress disorder.

PMID- 24439314
TI  - Cytological alterations of nasal mucosa after nasal packing.
AB  - PURPOSE: To assess the efficacy, tolerability and cytological alterations of
      nasal mucosa with various materials for nasal packing. MATERIALS AND METHODS: One
      hundred and five patients, submitted to a nasal surgery and post-operative
      packing with four different materials (Clauden(r), Merocel(r), two-fingered glove
      pack with gauzes inside and LyofoamTM) were prospectively enrolled in the study.
      All patients were submitted to a questionnaire of 12 questions which required the
      patients to refer to the tolerability of packing. Finally a nasal cytological
      test was performed after removal of packing and 10 days after, to evidence the
      alterations of ciliated cells and reduction of supranuclear stria. RESULTS: The
      questionnaire of tolerability of packing revealed a severe discomfort (grade III)
      in 13 patients (38.2%) with Clauden, 1 (2.4%) with Merocel, 7 (41.1%) with two
      fingered glove packing and 6 (46.1%) with Lyofon. As regards cellular
      alterations, the two-fingered glove and the Merocel groups had the lowest
      percentage of cellular alterations which was particularly different from the
      Clauden group (p=.0014) The supranuclear stria was reduced in the Clauden group
      and the two-fingered glove packing group both after packing removal and after ten
      days with a statistical difference when compared to the other two groups
      (p<.001). CONCLUSIONS: Merocel packing appears to be well tolerated by the
      patients with the lowest percentage of cytological alteration, of ciliated cells.
      Also finger glove packing shows scarce damage of nasal mucosa with a lower
      percentage of nasal bleeding but its tolerability is not so good.

PMID- 24439313
TI  - Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a
      randomised trial.
AB  - BACKGROUND: Patients with isolated locoregional recurrences (ILRR) of breast
      cancer have a high risk of distant metastasis and death from breast cancer. We
      aimed to establish whether adjuvant chemotherapy improves the outcome of such
      patients. METHODS: The CALOR trial was a pragmatic, open-label, randomised trial
      that accrued patients with histologically proven and completely excised ILRR
      after unilateral breast cancer who had undergone a mastectomy or lumpectomy with
      clear surgical margins. Eligible patients were enrolled from hospitals worldwide
      and were centrally randomised (1:1) to chemotherapy (type selected by the
      investigator; multidrug for at least four courses recommended) or no
      chemotherapy, using permuted blocks, and stratified by previous chemotherapy,
      oestrogen-receptor and progesterone-receptor status, and location of ILRR.
      Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine
      therapy, radiation therapy was mandated for patients with microscopically
      involved surgical margins, and anti-HER2 therapy was optional. The primary
      endpoint was disease-free survival. All analyses were by intention to treat. This
      study is registered with ClinicalTrials.gov, number NCT00074152. FINDINGS: From
      Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive
      chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of
      4.9 years (IQR 3.6-6 .0), 24 (28%) patients had disease-free survival events in
      the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5
      year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57%
      (44-67) without chemotherapy (hazard ratio 0.59 [95% CI 0.35-0.99]; p=0.046).
      Adjuvant chemotherapy was significantly more effective for women with oestrogen
      receptor-negative ILRR (pinteraction=0.046), but analyses of disease-free
      survival according to the oestrogen-receptor status of the primary tumour were
      not statistically significant (pinteraction=0.43). Of the 81 patients who
      received chemotherapy, 12 (15%) had serious adverse events. The most common
      adverse events were neutropenia, febrile neutropenia, and intestinal infection.
      INTERPRETATION: Adjuvant chemotherapy should be recommended for patients with
      completely resected ILRR of breast cancer, especially if the recurrence is
      oestrogen-receptor negative. FUNDING: US Department of Health and Human Services,
      Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology
      Research Foundation, Australian and New Zealand Breast Cancer Trials Group,
      Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa,
      Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Espanol de
      Investigacion en Cancer de Mama (GEICAM), and the Dutch Breast Cancer Trialists'
      Group (BOOG).

PMID- 24439315
TI  - Is a redefinition of the growth criteria of vestibular schwannomas needed?
AB  - PURPOSE: The natural history of vestibular schwannomas is poorly understood.
      Knowledge of growth rate and growth pattern is essential because the treatment
      strategy is based upon these. The purpose of this study was to determine the
      inter- and intraobserver variability in measuring VS size. MATERIALS AND METHODS:
      Two consultant neuroradiologists independently made three linear measurements
      (d1, d2, d3) using digital MRI scans. MRI scans from 72 patients diagnosed
      between 2002 and 2010 with VS were obtained. These patients had a total of 223
      MRI scans. d1 (medio-lateral diameter) was made perpendicular to d2. d2 was made
      parallel to the posterior border of the petrous ridge, and d3 was a measure of
      the cranio-caudal height of the tumor. RESULTS: Limits of Agreement ranges are
      larger for interobserver reliability compared to intraobserver reliability.
      Measurement error for all diameters (except d1, intraobserver) is greater than
      2mm. d1 measurements had the least variability and d3 measurements the highest
      variability, both for intra and interobserver measurements. CONCLUSIONS: The
      optimal method of estimating VS size needs further investigation, and
      measurements need to be standardized and clearly defined. d3 seems to be the most
      difficult diameter to measure reliably. Interobserver measurement error for all
      diameters is greater than 2mm. The current VS growth criterion of more than 1
      2mm, used to triage patients to surgery, lies within this error range, and thus
      is problematic as a guide for clinical practice. We therefore suggest that the
      growth criterion for VS be redefined.

PMID- 24439316
TI  - Emerging organic contaminants in coastal waters: anthropogenic impact,
      environmental release and ecological risk.
AB  - This study provides a first estimate of the sources, distribution, and risk
      presented by emerging organic contaminants (EOCs) in coastal waters off
      southwestern Taiwan. Ten illicit drugs, seven nonsteroidal anti-inflammatory
      drugs (NSAIDs), five antibiotics, two blood lipid regulators, two antiepileptic
      drugs, two UV filters, caffeine, atenolol, and omeprazole were analyzed by solid
      phase extraction and liquid chromatography coupled to tandem mass spectrometry
      (SPE-LC-MS/MS). Thirteen EOCs were detected in coastal waters, including four
      NSAIDs (acetaminophen, ibuprofen, ketoprofen, and codeine), three antibiotics
      (ampicillin, erythromycin, and cefalexin), three illicit drugs (ketamine,
      pseudoephedrine, and MDMA), caffeine, carbamazepine, and gemfibrozil. The median
      concentrations for the 13 EOCs ranged from 1.47 ng/L to 156 ng/L. Spatial
      variation in concentration of the 13 EOCs suggests discharge into coastal waters
      via ocean outfall pipes and rivers. Codeine and ampicillin have significant
      pollution risk quotients (RQ>1), indicating potentially high risk to aquatic
      organisms in coastal waters.

PMID- 24439317
TI  - Discussion.

PMID- 24439318
TI  - Morphologic evaluation of ruptured and symptomatic abdominal aortic aneurysm by
      three-dimensional modeling.
AB  - OBJECTIVE: To identify geometric indices of abdominal aortic aneurysms (AAAs) on
      computed tomography that are associated with higher risk of rupture. METHODS:
      This retrospective case-control, institutional review board-approved study
      involved 63 cases with ruptured or symptomatic AAA and 94 controls with
      asymptomatic AAA. Three-dimensional models were generated from computed
      tomography segmentation and used for the calculation of 27 geometric indices. On
      the basis of the results of univariate analysis and multivariable sequential
      logistic regression analyses with a forward stepwise model selection based on
      likelihood ratios, a traditional model based on gender and maximal diameter
      (Dmax) was compared with a model that also incorporated geometric indices while
      adjusting for gender and Dmax. Receiver operating characteristic (ROC) curves
      were calculated for these two models to evaluate their classification accuracy.
      RESULTS: Univariate analysis revealed that gender (P = .024), Dmax (P = .001),
      and 14 other geometric indices were associated with AAA rupture at P < .05. In
      the multivariable analysis, adjusting for gender and Dmax, the AAA with a higher
      bulge location (P = .020) and lower mean averaged area (P = .005) were associated
      with AAA rupture. With these two geometric indices, the area under the ROC curve
      showed an improvement from 0.67 (95% confidence interval, 0.58-0.77) to 0.75 (95%
      confidence interval, 0.67-0.83; P < .001). Our predictive model showed comparable
      sensitivity (64% vs 60%) and specificity (79% vs 77%) with current treatment
      criteria based on gender and diameter at the point optimizing the Youden index
      (sensitivity + specificity - 1) on the ROC curve. CONCLUSIONS: Two geometric
      indices derived from AAA three-dimensional modeling were independently associated
      with AAA rupture. The addition of these indices in a predictive model based on
      current treatment criteria modestly improved the accuracy to detect aneurysm
      rupture.

PMID- 24439320
TI  - The training of firemen.

PMID- 24439319
TI  - Castration of male mice prevents the progression of established angiotensin II
      induced abdominal aortic aneurysms.
AB  - OBJECTIVE: Male sex is a nonmodifiable risk factor for abdominal aortic aneurysm
      (AAA) development. Similar to humans, male mice are more susceptible to
      angiotensin II (AngII)-induced AAAs than female mice. Previous studies
      demonstrated that castration of males markedly reduced the formation of AngII
      induced AAAs. Progression of AAA size is associated with increased risk of
      aneurysm rupture. In this study, we hypothesized that castration of male mice
      would reduce the progression of established AngII-induced AAAs. METHODS: Male
      apolipoprotein E-deficient mice were infused with AngII for 1 month to induce AAA
      formation. Aortic diameters were measured by ultrasound imaging, and mice were
      stratified into two groups that underwent a sham operation or castration. AngII
      infusions were continued for a further 2 months. Ultrasound imaging was used to
      quantify lumen diameters, and excised aortas were processed for quantification of
      AAA size, volume, and tissue characteristics. RESULTS: Sham-operated mice
      exhibited progressive dilation of suprarenal aortic lumen diameters during the
      continued AngII infusion. Aortic lumen diameters were significantly decreased in
      castrated mice (n = 17) compared with sham-operated mice (n = 15) at study end
      point (1.63 +/- 0.04 vs 1.88 +/- 0.05 mm; P < .05). However, maximal external AAA
      diameters were not significantly different between sham-operated and castrated
      mice. The vascular volume/lumen volume ratio of excised AAAs imaged by ultrasound
      was significantly increased by castration (9.5% +/- 2.0%) vs sham operation (4.8%
      +/- 0.9%; n = 11 per group; P < .05). Moreover, compared with the thin-walled
      AAAs of sham-operated mice, aneurysm sections from castrated mice exhibited
      increased smooth muscle alpha-actin and collagen. CONCLUSIONS: Removal of
      endogenous male hormones by castration selectively reduces aortic lumen expansion
      while not altering the external AAA dimensions. CLINICAL RELEVANCE: There are no
      therapeutics that slow the progression of abdominal aortic aneurysms (AAAs), and
      as the size of an AAA increases, so does the risk of rupture and death. Male sex
      is a nonmodifiable risk factor for AAA development, but whether male sex hormones
      have a similar effect on AAA progression is unclear. Removal of male sex hormones
      in an established mouse model of angiotensin II-induced AAAs resulted in reduced
      progressive lumen dilation while not altering external AAA dimensions. Therapies
      that limit androgen action may provide benefit against AAA progression.
      Alternatively, supplemental testosterone may be contraindicated in men diagnosed
      with an AAA.

PMID- 24439321
TI  - Influence of computed tomography angiography reconstruction software on anatomic
      measurements and endograft component selection for endovascular abdominal aortic
      aneurysm repair.
AB  - OBJECTIVE: Three-dimensional (3D) centerline reconstruction of computed
      tomography angiography (CTA) images permits detailed anatomic characterization of
      abdominal aortic aneurysms and facilitates planning of endovascular repair.
      Although several programs for 3D CTA reconstruction and measurement are
      available, direct comparisons have not been published, and reliability between
      software platforms has not been characterized. We evaluated agreement between
      anatomic measurements obtained from 3D CTA reconstructions using three
      commercially available software programs and characterized concordance between
      the programs for endograft component selection. METHODS: Images from 92 CTA
      studies performed before abdominal aortic aneurysm repair were reconstructed and
      measured using three different software programs: independent reconstruction with
      proprietary software (Preview; M2S Inc, Lebanon, NH), surgeon-based
      reconstruction with proprietary software (AquariusNet Thin Client; TeraRecon Inc,
      San Mateo, Calif), and surgeon-based reconstruction with open-source software
      (Osirix MD; Pixmeo, Geneva, Switzerland). Agreement between outer wall diameter
      and length measurements obtained from centerline reconstructions created with
      each program was evaluated using scatter plots, intraclass correlation
      coefficients, and Bland-Altman plots. Concordance between aortic and iliac
      endograft component diameters selected from measurements with each program based
      on published instructions for use was examined using weighted kappa statistics.
      RESULTS: Diameter measurements were generally similar between programs. Mean
      diameters at all locations were within <= 1 mm of one another, and mean length
      measurements were within <= 10 mm of one another for all pairwise comparisons.
      Intraclass correlations coefficients between programs for diameter measurements
      were comparable between programs (>= 0.82 for all diameter comparisons and >=
      0.88 for all length comparisons) and indicated good correlation. Pair-wise
      comparisons indicated similar rates of identical and adjacent size endograft
      component selection without an obvious trend toward superior agreement for any
      two programs. Rates of identical proximal endograft diameter selection ranged
      from 46% to 59%, whereas 89% to 100% of proximal endograft diameters selected
      between programs were within one adjacent (smaller or larger) size of each other.
      For iliac endograft selection, rates of identical component diameter selection
      between programs ranged from 36% to 69%, and 58% to 99% of selected iliac
      endograft diameters were within one adjacent size. CONCLUSIONS: Outer wall
      diameter and centerline length measurements obtained from 3D CTA reconstructions
      demonstrated good correlation between imaging analysis software programs, and
      graft diameter selections based on these measurements were reasonably similar.
      Comparable 3D CTA reconstruction measurements can be generated from independent
      and surgeon-based approaches using proprietary and open-source software, and the
      selection of a method to interpret images for endograft planning can be
      individualized according to operator experience and available resources while
      retaining sufficient accuracy.

PMID- 24439323
TI  - Superficialization of brachial artery as effective alternative vascular access.
AB  - OBJECTIVE: The Japanese Society for Dialysis Therapy recommends
      superficialization of the brachial artery (BA) as an alternative vascular access
      (VA) technique in patients for whom a conventional internal shunt (arteriovenous
      fistula [AVF] or arteriovenous graft) cannot be created. Although 2% to 3% of
      Japanese hemodialysis patients undergo this procedure, it is not well recognized
      worldwide. We report here our experience with the procedure, as well as
      indications, durability, and morbidity. METHODS: The technique involves exposure
      of the BA and ligation of the side branches, then fixing it beneath the skin at
      the upper arm. Cannulation of the BA is performed 2 weeks or more after surgery,
      and it is used as an outflow route, with any vein in an upper extremity utilized
      for blood return, including the hand if sites in the arm are not accessible. We
      retrospectively reviewed our cases of superficialization of the BA for VA.
      RESULTS: From 2005 through 2008, a total of 24 patients (11 females [46%];
      average age, 69 years [range, 39-84 years]) underwent superficialization of the
      BA, of whom eight (33%) had diabetes. The indications were (1) impaired cardiac
      function (n = 13); (2) no other prospect for AVF or patient refused prosthetic
      graft implantation (n = 5); (3) severe upper extremity arterial disease or
      ischemic steal syndrome requiring AVF closure (n = 3); (4) venous hypertension
      with central vein occlusion (n = 2); and (5) repeated AVF thrombosis due to
      heparin-induced thrombocytopenia (n = 1). The mean follow-up period was 28
      months. Serious complications were seen in one patient with an infected
      pseudoaneurysm formation associated with a BA puncture, which necessitated BA
      ligation, while two patients required an aneurysmectomy with reconstruction and
      one had occlusion of the superficialized BA, though no clinical symptoms of hand
      ischemia developed. We also had difficulty finding a vein for blood return in
      five patients. The rate of superficialized BA patency as a functioning VA was 95%
      and 66% at 1 and 3 years, respectively. CONCLUSIONS: Superficialization of the BA
      was found to be a simple and safe technique, with acceptable durability and
      complication rate in selected Japanese hemodialysis patients. We consider that
      this shuntless VA permits adequate blood flow and has theoretical advantages for
      some patients, particularly those with impaired cardiac function, though the
      availability of a return vein is a prerequisite for a functioning VA.

PMID- 24439324
TI  - A systematic review and meta-analysis of abdominal compartment syndrome after
      endovascular repair of ruptured abdominal aortic aneurysms.
AB  - OBJECTIVE: Limited data exist regarding the development of abdominal compartment
      syndrome (ACS) after endovascular repair of ruptured abdominal aortic aneurysms
      (RAAAs). We aimed to record the incidence, management, and outcome of this
      complication. METHODS: A systematic review and meta-analysis of the English
      language literature was undertaken through June 2012. Articles reporting data on
      outcome after endovascular repair of RAAAs were identified, and information
      regarding ACS was sought. RESULTS: Included were 39 eligible studies reporting
      1134 patients. The pooled perioperative mortality was 21% (95% confidence
      interval [CI], 18%-24%). A total of 109 cases of ACS were recorded. There was
      significant within-study heterogeneity (Cochran Q = 94.1; P < .0001), and the
      pooled ACS rate was 8% (95% CI, 5.6%-10.8%). Only six studies accurately defined
      ACS, and four focused specifically on ACS. When the meta-analysis was repeated
      after including only studies with a definition and those focusing on ACS, the
      pooled rate increased to 17% (95% CI, 10%-26%) and 21% (95% CI, 13%-30%),
      respectively. A random-effects meta-regression analysis investigating the effect
      of ACS and other risk factors on mortality revealed a significant linear
      correlation between hemodynamic instability and death (r = 0.303) and a nonlinear
      (second degree polynomial) association between bifurcated endograft approach and
      death (R(2) = 0.348; P = .0027). However, no statistically significant
      association could be found between ACS and death. A further meta-regression
      analysis failed to identify any statistically significant predictors of ACS.
      Treatment included open decompression in 86 patients, percutaneous drainage in 18
      (catheter only in five, combined with tissue plasminogen activator infusion in
      13), and conservative measures in five. Data on outcome of ACS were only
      available for 76 patients; 35 of these died, for a mortality rate of 47%.
      CONCLUSIONS: The pooled ACS rate was calculated at 8%, but this figure may be
      >20% with improved awareness and vigilant monitoring. Although no statistically
      significant association could be found between ACS and death, almost half the
      patients who developed ACS after endovascular repair of RAAAs were likely to die.

PMID- 24439322
TI  - Home versus in-hospital treatment of outpatients with acute deep venous
      thrombosis of the lower limbs.
AB  - BACKGROUND: Some physicians are still concerned about the safety of treatment at
      home of patients with acute deep venous thrombosis (DVT). METHODS: We used data
      from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) registry
      to compare the outcomes in consecutive outpatients with acute lower limb DVT
      according to initial treatment at home or in the hospital. A propensity score
      matching analysis was carried out with a logistic regression model. RESULTS: As
      of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were
      treated at home. Patients treated at home were more likely to be male and younger
      and to weigh more; they were less likely than those treated in the hospital to
      have chronic heart failure, lung disease, renal insufficiency, anemia, recent
      bleeding, immobilization, or cancer. During the first week of anticoagulation, 27
      patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and
      51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home
      were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled,
      and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis,
      patients treated at home had a similar rate of venous thromboembolism recurrences
      and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1
      1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the
      first week compared with those treated in the hospital. CONCLUSIONS: In
      outpatients with DVT, home treatment was associated with a better outcome than
      treatment in the hospital. These data may help safely treat more DVT patients at
      home.

PMID- 24439325
TI  - Perioperative management with antiplatelet and statin medication is associated
      with reduced mortality following vascular surgery.
AB  - OBJECTIVE: Many patients undergoing vascular surgical procedures are not on
      appropriate medical therapy. This study sought to examine the variation and
      impact of antiplatelet (AP) and statin therapy on early and late mortality in
      patients undergoing vascular surgery in our region. METHODS: We studied all
      patients (n = 14,489) undergoing elective carotid endarterectomy (n = 6978),
      carotid stenting (n = 524), and suprainguinal (n = 763) and infrainguinal bypass
      (n = 3053), as well as patients with known coronary risk factors undergoing open
      (n = 1044) and endovascular (n = 2127) abdominal aortic aneurysm repair from 2005
      to 2012 in the Vascular Study Group of New England. Optimal medical management
      was defined as treatment with both AP and statin agents, preoperatively and at
      discharge. We analyzed temporal, procedural, and center variation of medication
      use. Multivariable analyses were used to determine the adjusted impact of AP and
      statin therapy on 30-day mortality and 5-year survival. RESULTS: Optimal medical
      management improved over the study interval (55% in 2005 to 68% in 2012; P trend
      < .01) with carotid interventions having the highest rates of optimal medications
      use (carotid artery stenting, 78%; carotid endarterectomy, 74%) and abdominal
      aortic aneurysm repair in patients with known cardiac risk factors having the
      lowest (open, 57%; endovascular aneurysm repair, 56%). Optimal medication use
      varied by center as well (range, 40%-86%). Preoperative AP and statin use was
      associated with reduced 30-day mortality (odds ratio, 0.76; 95% confidence
      interval [CI], 0.5-1.05; P = .09). AP and statin prescription at discharge was
      additive in survival benefit with improved 5-year survival (hazard ratio, 0.5;
      95% CI, 0.4-0.7; P < .01) that was consistent across procedure types. Patients
      prescribed AP and statin at discharge had 5-year survival of 79% (95% CI, 77%
      81%) compared with only 61% (95% CI, 52%-68%; P < .001) for patients on neither
      medication. CONCLUSIONS: AP and statin therapy preoperatively and at discharge
      was associated with reduced 30-day mortality and an absolute 18% improved 5-year
      survival after vascular surgery. However, one-third of patients are suboptimally
      managed in real world practice. This demonstrates an opportunity for quality
      improvement that can substantially improve survival after vascular surgery.

PMID- 24439326
TI  - Introduction to the special issue: Britton Chance 100th commemorative.

PMID- 24439327
TI  - Adaptable near-infrared spectroscopy fiber array for improved coupling to
      different breast sizes during clinical MRI.
AB  - RATIONALE AND OBJECTIVES: Near-infrared spectroscopy (NIRS) of breast can provide
      functional information on the vascular and structural compartments of tissues in
      regions identified during simultaneous magnetic resonance imaging (MRI). NIRS can
      be acquired during dynamic contrast-enhanced MRI (DCE-MRI) to accomplish image
      guided spectroscopy of the enhancing regions, potentially increasing the
      diagnostic specificity of the examination and reducing the number of biopsies
      performed as a result of inconclusive MRI breast imaging studies. MATERIALS AND
      METHODS: We combine synergistic attributes of concurrent DCE-MRI and NIRS with a
      new design of the clinical NIRS breast interface that couples to a standard MR
      breast coil and allows imaging of variable breast sizes. Spectral information
      from healthy volunteers and cancer patients is recovered, providing molecular
      information in regions defined by the segmented MR image volume. RESULTS: The new
      coupling system significantly improves examination utility by allowing improved
      coupling of the NIR fibers to breasts of all cup sizes and lesion locations. This
      improvement is demonstrated over a range of breast sizes (cup size A through D)
      and normal tissue heterogeneity using a group of eight healthy volunteers and two
      cancer patients. Lesions located in the axillary region and medial-posterior
      breast are now accessible to NIRS optodes. Reconstructed images were found to
      have biologically plausible hemoglobin content, oxygen saturation, and water and
      lipid fractions. CONCLUSIONS: In summary, a new NIRS/MRI breast interface was
      developed to accommodate the variation in breast sizes and lesion locations that
      can be expected in clinical practice. DCE-MRI-guided NIRS quantifies total
      hemoglobin, oxygenation, and scattering in MR-enhancing regions, increasing the
      diagnostic information acquired from MR examinations.

PMID- 24439329
TI  - Noninvasive optical quantification of cerebral venous oxygen saturation in
      humans.
AB  - RATIONALE AND OBJECTIVES: Cerebral oxygen extraction, defined as the difference
      between arterial and venous oxygen saturations (SaO2 and SvO2), is a critical
      parameter for managing intensive care patients at risk for neurological collapse.
      Although quantification of SaO2 is easily performed with pulse oximetry or
      moderately invasive arterial blood draws in peripheral vessels, cerebral SvO2 is
      frequently not monitored because of the invasiveness and risk associated with
      obtaining jugular bulb or super vena cava (SVC) blood samples. MATERIALS AND
      METHODS: In this study, near-infrared spectroscopy (NIRS) was used to
      noninvasively measure cerebral SvO2 in anesthetized and mechanically ventilated
      pediatric patients (n = 10). To quantify SvO2, the NIRS signal component that
      fluctuates at the respiration frequency is isolated. This respiratory component
      is dominated by the venous portion of the interrogated vasculature. The NIRS
      measurements of SvO2 were validated against the clinical gold standard:
      invasively measured oxygen saturations from SVC blood samples. This technique was
      also applied in healthy volunteers (n = 5) without mechanical ventilation to
      illustrate its potential for use in healthy populations with natural airways.
      RESULTS: Ten pediatric patients with pulmonary hypertension were studied. In
      these patients, SvO2 in the SVC exhibited good agreement with NIRS-measured SvO2
      (R(2) = 0.80, P = .001, slope = 1.16 +/- 0.48). Furthermore, in the healthy adult
      volunteers, mean (standard deviation) NIRS-measured SvO2 was 79.4 (6.8)%. This
      value is in good agreement with the expected average central venous saturation
      reported in literature. CONCLUSION: Respiration frequency-selected NIRS can
      noninvasively quantify cerebral SvO2. This bedside technique can be used to help
      assess brain health in neurologically unstable patients.

PMID- 24439330
TI  - Microvascular versus macrovascular cerebral vasomotor reactivity in patients with
      severe internal carotid artery stenosis or occlusion.
AB  - RATIONALE AND OBJECTIVES: In patients with severe internal carotid artery steno
      occlusive lesions (ISOL), impaired cerebrovascular reactivity (CVR) is predictive
      of future ischemic stroke (IS) or transient ischemic attack (TIA). Therefore, the
      evaluation of CVR in ISOL patients may be a means to evaluate the risk for IS/TIA
      and decide on an intervention. Our aim was (1) to explore the feasibility of
      concurrent near-infrared spectroscopy (NIRS-DOS), diffuse correlation
      spectroscopy, and transcranial Doppler for CVR assessment in ISOL patients, and
      (2) to compare macrovascular and microvascular CVR in ISOL patients and explore
      its potential for IS/TIA risk stratification. MATERIALS AND METHODS: Twenty-seven
      ISOL patients were recruited. The changes in continuous microvascular and
      macrovascular hemodynamics upon acetazolamide injection were used to determine
      CVR. RESULTS: Oxyhemoglobin (HbO2, by near-infrared spectroscopy), microvascular
      cerebral blood flow (CBF, by diffuse correlation spectroscopy) and CBF velocity
      (by transcranial Doppler) showed significant increases upon acetazolamide
      injection in all subjects (P < .03). Only macrovascular CVR (P = .024) and none
      of the microvascular measures were significantly dependent on the presence of
      ISOL. In addition, while CBF was significantly correlated with HbO2, neither of
      these microvascular measures correlated with macrovascular CBF velocity.
      CONCLUSIONS: We demonstrated the simultaneous, continuous, and noninvasive
      evaluation of CVR at both the microvasculature and macrovasculature. We found
      that macrovascular CVR response depends on the presence of ISOL, whereas the
      microvascular CVR did not significantly depend on the ISOL presence, possibly due
      to the role of collaterals other than those of the circle of Willis. The
      concurrent microvascular and macrovascular CVR measurement in the ISOL patients
      might improve future IS/TIA risk assessment.

PMID- 24439328
TI  - Blood flow reduction in breast tissue due to mammographic compression.
AB  - RATIONALE AND OBJECTIVES: This study measures hemodynamic properties such as
      blood flow and hemoglobin concentration and oxygenation in the healthy human
      breast under a wide range of compressive loads. Because many breast-imaging
      technologies derive contrast from the deformed breast, these load-dependent
      vascular responses affect contrast agent-enhanced and hemoglobin-based breast
      imaging. METHODS: Diffuse optical and diffuse correlation spectroscopies were
      used to measure the concentrations of oxygenated and deoxygenated hemoglobin,
      lipid, water, and microvascular blood flow during axial breast compression in the
      parallel-plate transmission geometry. RESULTS: Significant reductions (P < .01)
      in total hemoglobin concentration (~30%), blood oxygenation (~20%), and blood
      flow (~87%) were observed under applied pressures (forces) of up to 30 kPa (120
      N) in 15 subjects. Lipid and water concentrations changed <10%. CONCLUSIONS:
      Imaging protocols based on injected contrast agents should account for variation
      in tissue blood flow due to mammographic compression. Similarly, imaging
      techniques that depend on endogenous blood contrasts will be affected by breast
      compression during imaging.

PMID- 24439331
TI  - Monitoring hemodynamic and metabolic alterations during severe hemorrhagic shock
      in rat brains.
AB  - RATIONALE AND OBJECTIVES: Our long-term goals are to identify imaging biomarkers
      for hemorrhagic shock and to understand how the preservation of cerebral
      microcirculation works. We also seek to understand how the damage occurs to the
      cerebral hemodynamics and the mitochondrial metabolism during severe hemorrhagic
      shock. MATERIALS AND METHODS: We used a multimodal cerebral cortex optical
      imaging system to obtain 4-hour observations of cerebral hemodynamic and
      metabolic alterations in exposed rat cortexes during severe hemorrhagic shock. We
      monitored the mean arterial pressure, heart rate, cerebral blood flow (CBF),
      functional vascular density (FVD), vascular perfusion and diameter, blood
      oxygenation, and mitochondrial reduced nicotinamide adenine dinucleotide (NADH)
      signals. RESULTS: During the rapid bleeding and compensatory stage, cerebral
      parenchymal circulation was protected by inhibiting the perfusion of dural
      vessels. During the compensatory stage, although the brain parenchymal CBF and
      FVD decreased rapidly, the NADH signal did not show a significant increase.
      During the decompensatory stage, FVD and CBF maintained the same low level and
      the NADH signal remained unchanged. However, the NADH signal showed a significant
      increase after the rapid blood infusion. FVD and CBF rebounded to the baseline
      after the resuscitation and then declined again. CONCLUSIONS: We present for the
      first time simultaneous imaging of cerebral hemodynamics and NADH signals in vivo
      during the process of hemorrhagic shock. This novel multimodal method
      demonstrated clearly that severe hemorrhagic shock imparts irreversible tissue
      damage that is not compensated by the autoregulatory mechanism. Hemodynamic and
      metabolic signatures including CBF, FVD, and NADH may be further developed to
      provide sensitive biomarkers for stage transitions in hemorrhagic shock.

PMID- 24439332
TI  - Practical steps for applying a new dynamic model to near-infrared spectroscopy
      measurements of hemodynamic oscillations and transient changes: implications for
      cerebrovascular and functional brain studies.
AB  - RATIONALE AND OBJECTIVES: Perturbations in cerebral blood volume (CBV), blood
      flow (CBF), and metabolic rate of oxygen (CMRO2) lead to associated changes in
      tissue concentrations of oxy- and deoxy-hemoglobin (DeltaO and DeltaD), which can
      be measured by near-infrared spectroscopy (NIRS). A novel hemodynamic model has
      been introduced to relate physiological perturbations and measured quantities. We
      seek to use this model to determine functional traces of cbv(t) and cbf(t) -
      cmro2(t) from time-varying NIRS data, and cerebrovascular physiological
      parameters from oscillatory NIRS data (lowercase letters denote the relative
      changes in CBV, CBF, and CMRO2 with respect to baseline). Such a practical
      implementation of a quantitative hemodynamic model is an important step toward
      the clinical translation of NIRS. MATERIALS AND METHODS: In the time domain, we
      have simulated O(t) and D(t) traces induced by cerebral activation. In the
      frequency domain, we have performed a new analysis of frequency-resolved
      measurements of cerebral hemodynamic oscillations during a paced breathing
      paradigm. RESULTS: We have demonstrated that cbv(t) and cbf(t) - cmro2(t) can be
      reliably obtained from O(t) and D(t) using the model, and that the functional
      NIRS signals are delayed with respect to cbf(t) - cmro2(t) as a result of the
      blood transit time in the microvasculature. In the frequency domain, we have
      identified physiological parameters (e.g., blood transit time, cutoff frequency
      of autoregulation) that can be measured by frequency-resolved measurements of
      hemodynamic oscillations. CONCLUSIONS: The ability to perform noninvasive
      measurements of cerebrovascular parameters has far-reaching clinical
      implications. Functional brain studies rely on measurements of CBV, CBF, and
      CMRO2, whereas the diagnosis and assessment of neurovascular disorders, traumatic
      brain injury, and stroke would benefit from measurements of local cerebral
      hemodynamics and autoregulation.

PMID- 24439334
TI  - Time-resolved MRI oximetry for quantifying CMRO(2) and vascular reactivity.
AB  - This brief review of magnetic resonance susceptometry summarizes the methods
      conceived in the authors' laboratory during the past several years. This article
      shows how venous oxygen saturation is quantified in large draining veins by field
      mapping and how this information, in concert with simultaneous measurement of
      cerebral blood flow, yields cerebral metabolic rate of oxygen, the brain's rate
      of oxygen consumption. The accuracy of this model-based approach in which the
      blood vessel is approximated as a long, straight cylinder, for which an
      analytical solution for the induced field exists, is discussed. It is shown that
      the approach is remarkably robust, allowing for time-resolved quantification of
      whole-brain metabolism at rest and in response to stimuli, thereby providing
      detailed information on cerebral physiology in health and disease not previously
      amenable by noninvasive methods. 

PMID- 24439333
TI  - Clinical EPR: unique opportunities and some challenges.
AB  - Electron paramagnetic resonance (EPR) spectroscopy has been well established as a
      viable technique for measurement of free radicals and oxygen in biological
      systems, from in vitro cellular systems to in vivo small animal models of
      disease. However, the use of EPR in human subjects in the clinical setting,
      although attractive for a variety of important applications such as oxygen
      measurement, is challenged with several factors including the need for
      instrumentation customized for human subjects, probe, and regulatory constraints.
      This article describes the rationale and development of the first clinical EPR
      systems for two important clinical applications, namely, measurement of tissue
      oxygen (oximetry) and radiation dose (dosimetry) in humans. The clinical
      spectrometers operate at 1.2 GHz frequency and use surface-loop resonators
      capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2
      measurements can be carried out noninvasively and repeatedly after placement of
      an oxygen-sensitive paramagnetic material (currently India ink) at the site of
      interest. Our EPR dosimetry system is capable of measuring radiation-induced free
      radicals in the tooth of irradiated human subjects to determine the exposure
      dose. These developments offer potential opportunities for clinical dosimetry and
      oximetry, which include guiding therapy for individual patients with tumors or
      vascular disease by monitoring of tissue oxygenation. Further work is in progress
      to translate this unique technology to routine clinical practice.

PMID- 24439335
TI  - The potential of hyperpolarized (13)C MRI in assessing signaling pathways in
      cancer.
AB  - Advances in genomics are enabling integration of various -omics to reveal the
      complexities underneath carcinogenesis. Multivariate signaling pathways are
      deregulated and evolve spatially and temporally depending on the tumor
      microenvironment. This finding shifts the focus of cancer research from "one
      disease-one target and drug" to "one disease-multiple pathway targets and
      combinational therapy" and imposes new challenges on the imaging community in
      terms of imaging targets, scales and information levels. In current clinical
      settings, most imaging modalities assess cancer risk through alternations in
      anatomy, function, metabolism, cellularity, or limited molecular events. Few
      clinical-translatable imaging modalities are capable of detecting aberrations in
      signaling pathways at the level of tissue biology. An exception to this is
      hyperpolarized (13)C magnetic resonance spectroscopic imaging (HP (13)C MRI),
      which is capable of imaging the molecular signatures of special metabolic enzymes
      using HP (13)C-labeled substrates. HP (13)C MRI can identify multiple metabolites
      including intermediates and products simultaneously to allow extraction of
      critical parameters such as flux alterations for multiple metabolic pathways.
      Meanwhile, recent progress in cancer metabolism research affirms that metabolic
      alterations are directly controlled by signaling pathways. Thus, in vivo
      assessment of aberrations occurring in signaling pathways becomes feasible
      through HP (13)C imaging. This report briefly reviews the connections between
      signaling pathways and cancer metabolic phenotypes, the current status of HP
      (13)C MRI in assessing signal pathways, and recent advances in HP (13)C MRI
      techniques. Integrated with cancer genomics and animal models, HP (13)C MRI may
      hold high promise in exploring important issues in cancer that are linked to
      functionality of signaling pathways. Examples include genomic-driven therapy,
      intratumoral heterogeneity, and drug resistances.

PMID- 24439337
TI  - The pivotal role of FDG-PET/CT in modern medicine.
AB  - The technology behind positron emission tomography (PET) and the most widely used
      tracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG), were both conceived in the 1970s,
      but the latest decade has witnessed a rapid emergence of FDG-PET as an effective
      imaging technique. This is not least due to the emergence of hybrid scanners
      combining PET with computed tomography (PET/CT). Molecular imaging has enormous
      potential for advancing biological research and patient care, and FDG-PET/CT is
      currently the most widely used technology in this domain. In this review, we
      discuss contemporary applications of FDG-PET and FDG-PET/CT as well as novel
      developments in quantification and potential future indications including the
      emerging new modality PET/magnetic resonance imaging. 

PMID- 24439336
TI  - Is higher lactate an indicator of tumor metastatic risk? A pilot MRS study using
      hyperpolarized (13)C-pyruvate.
AB  - RATIONALE AND OBJECTIVES: Cancer cells generate more lactate than normal cells
      under both aerobic and hypoxic conditions-exhibiting the so-called Warburg
      effect. However, the relationship between the Warburg effect and tumor metastatic
      potential remains controversial. We intend to investigate whether the higher
      lactate reflects higher tumor metastatic potential. MATERIALS AND METHODS: We
      used hyperpolarized (13)C-pyruvate magnetic resonance spectroscopy (MRS) to
      compare lactate (13)C-labeling in vivo in mouse xenografts of the highly
      metastatic (MDA-MB-231) and the relatively indolent (MCF-7) human breast cancer
      cell lines. We obtained the kinetic parameters of the lactate dehydrogenase (LDH)
      catalyzed reaction by three methods of data analysis including the differential
      equation fit, q-ratio fit, and ratio fit methods. RESULTS: Consistent results
      from the three methods showed that the highly metastatic tumors exhibited a
      smaller apparent forward rate constant (k(+) = 0.060 +/- 0.004 s(-1)) than the
      relatively indolent tumors (k(+) = 0.097 +/- 0.013 s(-1)). The ratio fit
      generated the greatest statistical significance for the difference (P = .02). No
      significant difference in the reverse rate constant was found between the two
      tumor lines. CONCLUSIONS: The result indicates that the less metastatic breast
      tumors may produce more lactate than the highly metastatic ones from the injected
      (13)C-pyruvate and supports the notion that breast tumor metastatic risk is not
      necessarily associated with the high levels of glycolysis and lactate production.
      More studies are needed to confirm whether and how much the measured apparent
      rate constants are affected by the membrane transporter activity and whether they
      are primarily determined by the LDH activity.

PMID- 24439338
TI  - Hierarchical clustering method to improve transrectal ultrasound-guided diffuse
      optical tomography for prostate cancer imaging.
AB  - The inclusion of anatomical prior information in reconstruction algorithms can
      improve the quality of reconstructed images in near-infrared diffuse optical
      tomography (DOT). Prior literature on possible locations of human prostate cancer
      from transrectal ultrasound (TRUS), however, is limited and has led to biased
      reconstructed DOT images. In this work, we propose a hierarchical clustering
      method (HCM) to improve the accuracy of image reconstruction with limited prior
      information. HCM reconstructs DOT images in three steps: 1) to reconstruct the
      human prostate, 2) to divide the prostate region into geometric clusters to
      search for anomalies in finer clusters, 3) to continue the geometric clustering
      within anomalies for improved reconstruction. We demonstrated this hierarchical
      clustering method using computer simulations and laboratory phantom experiments.
      Computer simulations were performed using combined TRUS/DOT probe geometry with a
      multilayered model; experimental demonstration was performed with a single-layer
      tissue simulating phantom. In computer simulations, two hidden absorbers without
      prior location information were reconstructed with a recovery rate of 100% in
      their locations and 95% in their optical properties. In experiments, a hidden
      absorber without prior location information was reconstructed with a recovery
      rate of 100% in its location and 83% in its optical property. 

PMID- 24439339
TI  - Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain
      and ultrasound imaging.
AB  - RATIONALE AND OBJECTIVES: The treatment of nonmelanoma skin cancer (NMSC) is
      usually by surgical excision or Mohs micrographic surgery and alternatively may
      include photodynamic therapy (PDT). To guide surgery and to optimize PDT,
      information about the tumor structure, optical parameters, and vasculature is
      desired. MATERIALS AND METHODS: Spatial frequency domain imaging (SFDI) can map
      optical absorption, scattering, and fluorescence parameters that can enhance
      tumor contrast and quantify light and photosensitizer dose. High frequency
      ultrasound (HFUS) imaging can provide high-resolution tumor structure and depth,
      which is useful for both surgery and PDT planning. RESULTS: Here, we present
      preliminary results from our recently developed clinical instrument for patients
      with NMSC. We quantified optical absorption and scattering, blood oxygen
      saturation (StO2), and total hemoglobin concentration (THC) with SFDI and lesion
      thickness with ultrasound. These results were compared to histological thickness
      of excised tumor sections. CONCLUSIONS: SFDI quantified optical parameters with
      high precision, and multiwavelength analysis enabled 2D mappings of tissue StO2
      and THC. HFUS quantified tumor thickness that correlated well with histology. The
      results demonstrate the feasibility of the instrument for noninvasive mapping of
      optical, physiological, and ultrasound contrasts in human skin tumors for surgery
      guidance and therapy planning.

PMID- 24439340
TI  - Mesoscopic fluorescence tomography of a photosensitizer (HPPH) 3D biodistribution
      in skin cancer.
AB  - RATIONALE AND OBJECTIVES: Photodynamic therapy (PDT) is a promising strategy for
      treating cancer. PDT involves three components: a photosensitizer (PS) drug, a
      specific wavelength of drug-activating light, and oxygen. A challenge in PDT is
      the unknown biodistribution of the PS in the target tissue. In this preliminary
      study, we report the development of a new approach to image in three dimensions
      the PS biodistribution in a noninvasive and fast manner. MATERIALS AND METHODS: A
      mesoscopic fluorescence tomography imaging platform was used to image
      noninvasively the biodistribution of 2-[1-hexyloxyethyl]-2 devinyl
      pyropheophorbide-a (HPPH) in preclinical skin cancer models. Seven tumors were
      imaged and optical reconstructions were compared to nonconcurrent ultrasound
      data. RESULTS: Successful imaging of the HPPH biodistribution was achieved on
      seven skin cancer tumors in preclinical models with a typical acquisition time of
      1 minute. Two-dimensional fluorescence signals and estimated three-dimensional PS
      distributions were located within the lesions. However, HPPH distribution was
      highly heterogeneous with the tumors. Moreover, HPPH distribution volume and
      tumor volume as estimated by ultrasound did not match. CONCLUSIONS: The results
      of this proof-of-concept study demonstrate the potential of MFMT to image rapidly
      the HPPH three-dimensional biodistribution in skin cancers. In addition, these
      preliminary data indicate that the PS biodistribution in skin cancer tumors is
      heterogeneous and does not match anatomical data. Mesoscopic fluorescence
      molecular tomography, by imaging fluorescence signals over large areas with high
      spatial sampling and at fast acquisition speeds, may be a new imaging modality of
      choice for planning and optimizing of PDT treatment.

PMID- 24439341
TI  - Advances in noninvasive functional imaging of bone.
AB  - The demand for functional imaging in clinical medicine is comprehensive. Although
      the gold standard for the functional imaging of human bones in clinical settings
      is still radionuclide-based imaging modalities, nonionizing noninvasive imaging
      technology in small animals has greatly advanced in recent decades, especially
      the diffuse optical imaging to which Britton Chance made tremendous
      contributions. The evolution of imaging probes, instruments, and computation has
      facilitated exploration in the complicated biomedical research field by allowing
      longitudinal observation of molecular events in live cells and animals. These
      research-imaging tools are being used for clinical applications in various
      specialties, such as oncology, neuroscience, and dermatology. The Bone, a deeply
      located mineralized tissue, presents a challenge for noninvasive functional
      imaging in humans. Using nanoparticles (NP) with multiple favorable properties as
      bioimaging probes has provided orthopedics an opportunity to benefit from these
      noninvasive bone-imaging techniques. This review highlights the historical
      evolution of radionuclide-based imaging, computed tomography, positron emission
      tomography, and magnetic resonance imaging, diffuse optics-enabled in vivo
      technologies, vibrational spectroscopic imaging, and a greater potential for
      using NPs for biomedical imaging.

PMID- 24439342
TI  - Stereotactic radiotherapy for large solitary brain metastases.
AB  - PURPOSE: To assess effectiveness and toxicity levels of stereotactic radiation
      therapy without whole brain radiation therapy in patients with solitary brain
      metastases larger than 3cm. PATIENTS AND METHODS: Between June 2007 and March
      2009, 12 patients received fractionated stereotactic radiation therapy and 24
      patients underwent stereotactic radiosurgery. For the fractionated stereotactic
      radiation therapy group, 3*7.7Gy were delivered to the planning target volume
      (PTV); median volume and diameter were 29.4 cm(3) and 4.4cm, respectively. For
      the stereotactic radiosurgery group, 14Gy were delivered to the PTV; median
      volume and diameter were 15.6 cm(3) and 3.7cm, respectively. RESULTS: Median
      follow-up was 218 days. For the fractionated stereotactic radiation therapy
      group, local control rates were 100% at 360 days and 64% at 720 days; for the
      stereotactic radiosurgery group, rates were 58% at 360 days and 48% at 720 days
      (P=0.06). Median survival time was 504 days for the fractionated stereotactic
      radiation therapy group and 164 days for the stereotactic radiosurgery group
      (P=0.049). Two cases of grade 2 toxicity were observed in the fractionated
      stereotactic radiation therapy group, and 6 cases of grade 1-2 toxicity, in the
      stereotactic radiosurgery group. CONCLUSIONS: This study provides data to support
      that fractionated stereotactic radiation therapy without whole brain radiation
      therapy with a margin dose of 3 fractions of 7.7Gy for treatment of solitary
      large brain metastases is efficient and well-tolerated. Because of the
      significant improvement in overall survival, this schedule should be assessed in
      a randomized trial.

PMID- 24439343
TI  - Discrimination, racial bias, and telomere length in African-American men.
AB  - BACKGROUND: Leukocyte telomere length (LTL) is an indicator of general systemic
      aging, with shorter LTL being associated with several chronic diseases of aging
      and earlier mortality. Identifying factors related to LTL among African Americans
      may yield insights into mechanisms underlying racial disparities in health.
      PURPOSE: To test whether the combination of more frequent reports of racial
      discrimination and holding a greater implicit anti-black racial bias is
      associated with shorter LTL among African-American men. METHODS: Cross-sectional
      study of a community sample of 92 African-American men aged between 30 and 50
      years. Participants were recruited from February to May 2010. Ordinary least
      squares regressions were used to examine LTL in kilobase pairs in relation to
      racial discrimination and implicit racial bias. Data analysis was completed in
      July 2013. RESULTS: After controlling for chronologic age and socioeconomic and
      health-related characteristics, the interaction between racial discrimination and
      implicit racial bias was significantly associated with LTL (b=-0.10, SE=0.04,
      p=0.02). Those demonstrating a stronger implicit anti-black bias and reporting
      higher levels of racial discrimination had the shortest LTL. Household income-to
      poverty threshold ratio was also associated with LTL (b=0.05, SE=0.02, p<0.01).
      CONCLUSIONS: Results suggest that multiple levels of racism, including
      interpersonal experiences of racial discrimination and the internalization of
      negative racial bias, operate jointly to accelerate biological aging among
      African-American men. Societal efforts to address racial discrimination in
      concert with efforts to promote positive in-group racial attitudes may protect
      against premature biological aging in this population.

PMID- 24439344
TI  - Temporal shifts in cardiovascular risk factor distribution.
AB  - BACKGROUND: Complementary strategies to shift risk factor population
      distributions and target high-risk individuals are required to reduce the burden
      of type 2 diabetes and cardiovascular disease (CVD). PURPOSE: To examine secular
      changes in glucose and CVD risk factors over 20 years during an individual and
      population-based CVD prevention program in Vasterbotten County, Sweden. METHODS:
      Population-based health promotion intervention was conducted and annual
      invitation for individuals turning 40, 50, and 60 years to attend a health
      assessment, including an oral glucose tolerance test, biochemical measures, and a
      questionnaire. Data were collected between 1991 and 2010, analyzed in 2012 and
      available for 120,929 individuals. Linear regression modeling examined age
      adjusted differences in CVD risk factor means over time. Data were direct-age
      standardized to compare disease prevalence. RESULTS: Between 1991-1995 and 2006
      2010, mean age-adjusted cholesterol (men=-0.53, 95% CI=-0.55, -0.50 mmol/L;
      women=-0.48, 95% CI=-0.50, -0.45 mmol/L) and systolic blood pressure declined
      (men=-3.06, 95% CI=-3.43, -2.70 mm Hg; women=-5.27, 95% CI=-5.64, -4.90 mm Hg),
      with corresponding decreases in the age-standardized prevalence of hypertension
      and hyperlipidemia. Mean age-adjusted 2-hour plasma glucose (men=0.19, 95%
      CI=0.15, 0.23 mmol/L; women=0.08, 95% CI=0.04, 0.11 mmol/L) and BMI increased
      (men=1.12, 95% CI=1.04, 1.21; women=0.65, 95% CI=0.55, 0.75), with increases in
      the age-standardized prevalence of diabetes and obesity. CONCLUSIONS: These data
      demonstrate the potential of combined individual- and population-based approaches
      to CVD risk factor control and highlight the need for additional strategies
      addressing hyperglycemia and obesity.

PMID- 24439345
TI  - Sedentary behavior and mortality in older women: the Women's Health Initiative.
AB  - BACKGROUND: Although epidemiologic studies have shown associations between
      sedentary behavior and mortality, few have focused on older women with adequate
      minority representation and few have controlled for both physical activity and
      functional status. PURPOSE: The objective of this study was to determine the
      relationship between sedentary time and total; cardiovascular disease (CVD);
      coronary heart disease (CHD); and cancer mortality in a prospective, multiethnic
      cohort of postmenopausal women. METHODS: The study population included 92,234
      women aged 50-79 years at baseline (1993-1998) who participated in the Women's
      Health Initiative Observational Study through September 2010. Self-reported
      sedentary time was assessed by questionnaire and examined in 4 categories (<=4,
      >4-8, >=8-11, >11 hours). Mortality risks were examined using Cox proportional
      hazard models adjusting for confounders. Models were also stratified by age,
      race/ethnicity, body mass index, physical activity, physical function, and
      chronic disease to examine possible effect modification. Analyses were conducted
      in 2012-2013. RESULTS: The mean follow-up period was 12 years. Compared with
      women who reported the least sedentary time, women reporting the highest
      sedentary time had increased risk of all-cause mortality in the multivariate
      model (HR=1.12, 95% CI=1.05, 1.21). Results comparing the highest versus lowest
      categories for CVD, CHD, and cancer mortality were as follows: HR=1.13, 95%
      CI=0.99, 1.29; HR=1.27, 95% CI=1.04, 1.55; and HR=1.21, 95% CI=1.07, 1.37,
      respectively. For all mortality outcomes, there were significant linear tests for
      trend. CONCLUSIONS: There was a linear relationship between greater amounts of
      sedentary time and mortality risk after controlling for multiple potential
      confounders.

PMID- 24439346
TI  - Neighborhood park use by children: use of accelerometry and global positioning
      systems.
AB  - BACKGROUND: Although having a greater number of neighborhood parks may be
      associated with greater overall physical activity in children, information is
      lacking about the extent to which children actually use parks for physical
      activity. PURPOSE: This study combined accelerometer, GPS, GIS, and self-report
      methods to examine neighborhood park availability, perceived proximity, and use
      for physical activity in children. METHODS: Low- to middle-income children (aged
      8-14 years) (n=135) from suburban communities in Southern California wore an
      Actigraph accelerometer and GlobalSat BT-335 GPS device across 7 days to measure
      physical activity and park use, respectively. ArcGIS identified parks within a
      500-m residential buffer of children's homes. Parents reported perceptions of
      neighborhood park proximity through the Neighborhood Environment Walkability
      Survey (NEWS). Data were collected from March 2009 to December 2010, and analyzed
      in 2013. RESULTS: Fifty-four percent of families lived within 500 m of a park. Of
      these children, GPS data indicated that 16% used it more than 15 minutes and an
      additional 11% of children used it between 5 and 15 minutes during the 7-day
      study period. The odds of extended park use (>15 minutes) increased fourfold when
      the distance between home and the nearest neighborhood park decreased by 100 m.
      Additionally, the odds of any park use (>5 minutes) doubled when moving from the
      25th to the 75th percentile for park greenness/vegetation density. CONCLUSIONS:
      Although children's use of neighborhood parks was generally low, it increased
      substantially when parks were closer to children's homes and had greater
      vegetation density.

PMID- 24439347
TI  - Traffic-light labels and choice architecture: promoting healthy food choices.
AB  - BACKGROUND: Preventing obesity requires maintenance of healthy eating behaviors
      over time. Food labels and strategies that increase visibility and convenience of
      healthy foods (choice architecture) promote healthier choices, but long-term
      effectiveness is unknown. PURPOSE: Assess effectiveness of traffic-light labeling
      and choice architecture cafeteria intervention over 24 months. DESIGN:
      Longitudinal pre-post cohort follow-up study between December 2009 and February
      2012. Data were analyzed in 2012. SETTING/PARTICIPANTS: Large hospital cafeteria
      with a mean of 6511 transactions daily. Cafeteria sales were analyzed for (1) all
      cafeteria customers and (2) a longitudinal cohort of 2285 hospital employees who
      used the cafeteria regularly. INTERVENTION: After a 3-month baseline period,
      cafeteria items were labeled green (healthy); yellow (less healthy); or red
      (unhealthy) and rearranged to make healthy items more accessible. MAIN OUTCOME
      MEASURES: Proportion of cafeteria sales that were green or red during each 3
      month period from baseline to 24 months. Changes in 12- and 24-month sales were
      compared to baseline for all transactions and transactions by the employee
      cohort. RESULTS: The proportion of sales of red items decreased from 24% at
      baseline to 20% at 24 months (p<0.001), and green sales increased from 41% to 46%
      (p<0.001). Red beverages decreased from 26% of beverage sales at baseline to 17%
      at 24 months (p<0.001); green beverages increased from 52% to 60% (p<0.001).
      Similar patterns were observed for the cohort of employees, with the largest
      change for red beverages (23%-14%, p<0.001). CONCLUSIONS: A traffic-light and
      choice architecture cafeteria intervention resulted in sustained healthier
      choices over 2 years, suggesting that food environment interventions can promote
      long-term changes in population eating behaviors.

PMID- 24439348
TI  - Vaccinations given during pregnancy, 2002-2009: a descriptive study.
AB  - BACKGROUND: A number of studies have described influenza vaccination coverage
      during pregnancy but few publications have described rates of other vaccinations.
      PURPOSE: To describe vaccination rates during pregnancy in the Vaccine Safety
      Datalink (VSD), with particular focus on vaccinations contraindicated during
      pregnancy. METHODS: Pregnancies ending in 2002 through 2009 and vaccinations
      administered during these pregnancies were identified in the VSD. Vaccination
      rates per 1000 pregnancies during the study period were calculated by vaccine
      type, recommendation category, pregnancy year, maternal age, and trimester.
      Analyses were conducted in 2012-2013. RESULTS: In the VSD, 669,695 pregnancies
      and 141,389 vaccinations were identified. Trivalent inactivated influenza (TIV)
      was the most commonly administered vaccination (174.1 doses per 1000 pregnancies)
      and was most often administered during the 2nd and 3rd trimesters. The most
      common vaccines in the "consider if indicated" category were tetanus-diphtheria
      (6.1 per 1000) and hepatitis B (3.7 per 1000). Contraindicated vaccination was
      infrequent, and the majority of these were measles-mumps-rubella (MMR) (1.2 per
      1000); varicella (1.0 per 1000); and live-attenuated influenza vaccine (LAIV)
      (0.3 per 1000). Both "consider if indicated" and contraindicated vaccines were
      more frequently administered during early pregnancy. CONCLUSIONS: TIV was the
      most commonly administered vaccine. With the exception of TIV, other vaccines
      were most frequently administered during early pregnancy and among younger women,
      suggesting that vaccination may occur when the woman and/or provider are unaware
      of the pregnancy. Contraindicated vaccines were infrequently administered during
      pregnancy; however, given that some women received contraindicated vaccines later
      in pregnancy, clearer recommendations and improved provider education may be
      needed.

PMID- 24439350
TI  - Population health concerns during the United States' Great Recession.
AB  - BACKGROUND: Associations between economic conditions and health are usually
      derived from cost-intensive surveys that are intermittently collected with
      nonspecific measures (i.e., self-rated health). PURPOSE: This study identified
      how precise health concerns changed during the U.S. Great Recession analyzing
      Google search queries to identify the concern by the query content and their
      prevalence by the query volume. METHODS: Excess health concerns were estimated
      during the Great Recession (December 2008 through 2011) by comparing the
      cumulative difference between observed and expected (based on linear projections
      from pre-existing trends) query volume for hundreds of individual terms. As
      performed in 2013, the 100 queries with the greatest excess were ranked and then
      clustered into themes based on query content. RESULTS: The specific queries with
      the greatest relative excess were stomach ulcer symptoms and headache symptoms,
      respectively, 228% (95% CI=35, 363) and 193% (95% CI=60, 275) greater than
      expected. Queries typically involved symptomology (i.e., gas symptoms) and
      diagnostics (i.e., heart monitor) naturally coalescing into themes. Among top
      themes, headache queries were 41% (95% CI=3, 148); hernia 37% (95% CI=16, 142);
      chest pain 35% (95% CI=6, 313); and arrhythmia 32% (95% CI=3, 149) greater than
      expected. Pain was common with back, gastric, joint, and tooth foci, with the
      latter 19% (95% CI=4, 46) higher. Among just the top 100, there were roughly 205
      million excess health concern queries during the Great Recession. CONCLUSIONS:
      Google queries indicate that the Great Recession coincided with substantial
      increases in health concerns, hinting at how population health specifically
      changed during that time.

PMID- 24439349
TI  - Smoking-cessation e-referrals: a national dental practice-based research network
      randomized controlled trial.
AB  - BACKGROUND: Tobacco use is still the leading preventable cause of death and
      morbidity in the U.S. Web-assisted tobacco interventions are an effective but
      underutilized tool in assisting smokers with quitting. The dental visit is an
      excellent opportunity to assist smokers in quitting by referring them to these
      tobacco-cessation online programs. PURPOSE: The study purpose was to test two
      patient referral methods-paper referrals (information prescriptions) versus paper
      plus e-referrals-to a web-assisted smoking-cessation induction system. DESIGN:
      RCT that used implementation research methods. PARTICIPANTS/SETTING: A total of
      100 community-based dental practices were enrolled and 1814 smokers were referred
      to the web-assisted tobacco induction system. INTERVENTION: The study
      intervention was a proactive e-referral of smokers to a web-assisted tobacco
      induction system called Decide2Quit.org, and the control group used paper
      referrals (information prescriptions) to refer smokers to the Decide2Quit.org.
      MAIN OUTCOME MEASUREMENTS: The outcome measurements were the referral numbers,
      Decide2Quit registration numbers, and the smokers' quit rate. Data were collected
      in 2010-2011 and analyses were completed in 2012. RESULTS: Although total
      referrals from intervention practices was lower than control, subsequent
      proportions of registrations among smokers referred to Decide2Quit.org were
      nearly fourfold higher (adjusted mean percentages: 29.5% vs 7.6%, p<0.01) in
      intervention compared with control practices. Subsequent rates of cessation among
      referred smokers were threefold higher (adjusted mean percentages: 3.0% vs 0.8%,
      p=0.03) in intervention practices as compared with control. CONCLUSIONS:
      Intervention practices using the e-referral system had higher smoker registration
      numbers and higher quit smoking rates than the control practices. This study
      finds that e-referrals are effective in getting smokers to the web-assisted
      smoking-cessation induction system and in assisting with quitting that more than
      compensates for any additional effort that e-referrals require on the part of the
      practitioner. CLINICAL TRIAL REGISTRATION: DPBRN Hygienists Internet Quality
      Improvement in Tobacco Cessation (HiQuit); NCT01108432.

PMID- 24439351
TI  - Quality improvement activities of local health departments during the 2008-2010
      economic recession.
AB  - BACKGROUND: A review of the work of researchers in the field of quality reveals a
      connection between the use of quality improvement (QI) concepts and improved
      financial performance. The disconnect between the expanding role of public health
      and the levels of per capita spending to support this role suggests that local
      health departments with a change in funding might benefit by employing QI to
      increase service delivery efficiency. PURPOSE: To examine the relationship
      between changes in local health department (LHD) total revenue during the 2008
      2010 economic recession and changes in LHD quality improvement activities during
      the same period. METHODS: A matched-pairs study assessed change in revenue and
      associated change in QI activities at two points of time, 2008 and 2010. The
      study was completed in 2013. A proportional odds regression model estimated the
      adjusted ORs, measuring the association between change in QI activities and total
      revenue change, controlling for demographics, leadership QI training, and
      accreditation intention. RESULTS: Neither changes in revenue nor changes in
      expenses predicted change in QI activities in LHDs. Enhanced QI activities were
      found in LHDs led by a director with a master's degree, led by directors trained
      in QI, or those serving medium-sized (50,000-499,000) jurisdictions. CONCLUSIONS:
      This study revealed that neither changes in revenue nor changes in LHD expenses
      predict enhanced QI activities. Rather, improvements appear to be more related to
      characteristics of local health department leaders, which suggests areas to focus
      on for future efforts in public health services improvement.

PMID- 24439352
TI  - Beliefs and experimentation with electronic cigarettes: a prospective analysis
      among young adults.
AB  - BACKGROUND: Previous cross-sectional studies found that positive beliefs about
      electronic nicotine delivery systems (commonly known as electronic cigarettes or
      e-cigarettes) were associated with use of these products. However, the
      prospective association between these beliefs and subsequent use of e-cigarettes
      is unclear. PURPOSE: To identify the beliefs predicting subsequent use of e
      cigarettes. METHODS: A total of 1379 young adults (mean age=24.1 years) from the
      Minnesota Adolescent Community Cohort who reported never using e-cigarettes at
      baseline (collected Oct 2010-Mar 2011) and completed follow-up data collection
      (during Oct 2011-Mar 2012) were included in this analysis. Participants' beliefs
      about e-cigarettes (potential as quit aids, harmfulness and addictiveness
      relative to cigarettes) were asked at baseline (yes/no). At follow-up,
      participants were asked if they had ever used e-cigarettes. Logistic regression
      models were used to assess the associations between beliefs about e-cigarettes
      and subsequent experimentation. Analysis was conducted in 2012. RESULTS: At
      follow-up, 7.4% of the sample reported ever using e-cigarettes (21.6% among
      baseline current smokers, 11.9% among baseline former smokers, and 2.9% among
      baseline nonsmokers). Participants who believed e-cigarettes can help people quit
      smoking and perceived e-cigarettes to be less harmful than cigarettes at baseline
      were more likely to report experimenting with e-cigarettes at follow-up (p<0.05).
      These associations did not differ by smoking status. CONCLUSIONS: Given that
      young adults are still developing their tobacco use behaviors, informing them
      about the lack of evidence to support e-cigarettes as quit aids and the unknown
      health risk of e-cigarettes may deter young adults from trying these products.

PMID- 24439353
TI  - Crowdsourcing applications for public health.
AB  - Crowdsourcing is an online, distributed, problem-solving, and production model
      that uses the collective intelligence of networked communities for specific
      purposes. Although its use has benefited many sectors of society, it has yet to
      be fully realized as a method for improving public health. This paper defines the
      core components of crowdsourcing and proposes a framework for understanding the
      potential utility of crowdsourcing in the domain of public health. Four discrete
      crowdsourcing approaches are described (knowledge discovery and management;
      distributed human intelligence tasking; broadcast search; and peer-vetted
      creative production types) and a number of potential applications for
      crowdsourcing for public health science and practice are enumerated. 

PMID- 24439354
TI  - Primary care-based interventions for intimate partner violence: a systematic
      review.
AB  - CONTEXT: Primary care providers are uniquely positioned to respond to patients'
      disclosure of intimate partner violence (IPV). However, the research on primary
      care-based IPV interventions has not been systematically synthesized, making it
      difficult for providers, policymakers, and researchers to understand how to
      effectively intervene in the primary care setting. This systematic review
      summarizes primary care-based interventions for patients experiencing IPV.
      EVIDENCE ACQUISITION: PubMed, PsycINFO, and CINAHL were searched from their start
      through September 2012; this search was augmented by bibliographic review and
      consultation with experts. Eligible studies included English-language, peer
      reviewed articles that assessed patient-level impact of IPV interventions that
      originated from patients' visits to a primary care provider. EVIDENCE SYNTHESIS:
      Of 80 potentially eligible studies, 17 met eligibility criteria. The majority of
      interventions recruited women from reproductive care sites. Interventions tended
      to be brief, delivered by nonphysicians, and focused on empowerment, empathetic
      listening, discussion of the cycle of violence and safety, and referral to
      community-based resources. Thirteen studies demonstrated at least one
      intervention-related benefit. Six of 11 articles measuring IPV persistence found
      reductions in future violence; two of five measuring safety-promoting behaviors
      found increases; and six of ten measuring IPV/community resource referrals found
      enhanced use. Some studies also documented health improvements. CONCLUSIONS: The
      majority of studies demonstrated patient-level benefit subsequent to primary care
      IPV interventions, with IPV/community referrals the most common positively
      affected outcome.

PMID- 24439355
TI  - Active living research: creating and using evidence to support childhood obesity
      prevention.
AB  - The second phase of Active Living Research (ALR-2, 2007-2012) focused on
      advancing the Robert Wood Johnson Foundation (RWJF)'s goal of reversing the
      childhood obesity epidemic. The mission was to stimulate and support research to
      identify environmental factors and policies that influence physical activity for
      children and families to inform effective childhood obesity prevention
      strategies, with an emphasis on the lower-income and racial/ethnic communities
      with highest childhood obesity prevalence. The present report describes ALR
      activities undertaken to accomplish three goals. The first goal-to build an
      evidence base-was furthered by funding 230 competitive grants to identify and
      evaluate promising environment and policy changes. More than 300 publications
      have been produced so far. The second goal-to build an interdisciplinary and
      diverse field of investigators-was supported through annual conferences and
      linked journal supplements, academic outreach to multiple disciplines, and grants
      targeting young investigators and those representing groups historically
      disadvantaged or underrepresented in RWJF-funded research. The third goal-to use
      research to inform policy and practice-was advanced through research briefs;
      webinars; research-translation grants supporting ALR grantees to design
      communications tailored to decision-maker audiences; active engagement of
      policymakers and other stakeholders in ALR program meetings and annual
      conferences; ALR presentations at policy-related meetings; and broad outreach
      through a widely used website, e-mailed newsletters, and social media. ALR-2
      findings and products have contributed to a rapid increase in the evidence base
      and field of active living research, as documented by an independent program
      evaluation. 

PMID- 24439356
TI  - Evaluation of active living research: ten years of progress in building a new
      field.
AB  - BACKGROUND: The Robert Wood Johnson Foundation Active Living Research (ALR)
      program commissioned an evaluation of its initiative to assess 10 years (2001
      2011) of progress in establishing a new interdisciplinary field to develop and
      translate research focused on policy and environmental factors affecting physical
      activity in children and families. PURPOSE: The second-phase evaluation (ALR-2)
      was conducted from March to July 2011 to measure progression from evidence- and
      field-building (Goals 1 and 2) to policy and practice contributions (Goal 3) to
      inform childhood obesity strategies, and to develop recommendations for a third
      phase (ALR-3). METHODS: The evaluation was a retrospective, in-depth descriptive
      study utilizing qualitative and quantitative methods. Key informant interviews
      (N=100) across seven stakeholder groups were conducted and analyzed in 2011. Data
      from web-based surveys of grantee investigators conducted from 2007 to 2011 and
      analyzed in 2011 served as the primary quantitative source. RESULTS: Key
      indicators of ALR's overall progress confirmed ALR's success across its three
      goals: (1) establishing a strong research base: 309 publications filling major
      knowledge gaps; (2) building an interdisciplinary and diverse field: grantees
      represented 31 disciplines, with more than one quarter (28%) of investigators
      having <=5 years of experience, of which 39% were people of color; and (3) using
      research to inform policy and practice: 62 examples, of which slightly more than
      one half (n=32) resulted in actual policy or practice change. CONCLUSIONS:
      Overall, ALR met its three goals during ALR-2 and was well positioned to
      implement a third phase of the program to further accelerate the translation of
      its research into policy and practice.

PMID- 24439357
TI  - Human rights violations against women: acid violence in Bangladesh.

PMID- 24439358
TI  - Widening rural-urban disparities in life expectancy, U.S., 1969-2009.
AB  - BACKGROUND: There is limited research on rural-urban disparities in U.S. life
      expectancy. PURPOSE: This study examined trends in rural-urban disparities in
      life expectancy at birth in the U.S. between 1969 and 2009. METHODS: The 1969
      2009 U.S. county-level mortality data linked to a rural-urban continuum measure
      were analyzed. Life expectancies were calculated by age, gender, and race for 3
      year time periods between 1969 and 2004 and for 2005-2009 using standard life
      table methodology. Differences in life expectancy were decomposed by age and
      cause of death. RESULTS: Life expectancy was inversely related to levels of
      rurality. In 2005-2009, those in large metropolitan areas had a life expectancy
      of 79.1 years, compared with 76.9 years in small urban towns and 76.7 years in
      rural areas. When stratified by gender, race, and income, life expectancy ranged
      from 67.7 years among poor black men in nonmetropolitan areas to 89.6 among poor
      Asian/Pacific Islander women in metropolitan areas. Rural-urban disparities
      widened over time. In 1969-1971, life expectancy was 0.4 years longer in
      metropolitan than in nonmetropolitan areas (70.9 vs 70.5 years). By 2005-2009,
      the life expectancy difference had increased to 2.0 years (78.8 vs 76.8 years).
      The rural poor and rural blacks currently experience survival probabilities that
      urban rich and urban whites enjoyed 4 decades earlier. Causes of death
      contributing most to the increasing rural-urban disparity and lower life
      expectancy in rural areas include heart disease, unintentional injuries, COPD,
      lung cancer, stroke, suicide, and diabetes. CONCLUSIONS: Between 1969 and 2009,
      residents in metropolitan areas experienced larger gains in life expectancy than
      those in nonmetropolitan areas, contributing to the widening gap.

PMID- 24439359
TI  - Patterns of birth cohort-specific smoking histories, 1965-2009.
AB  - BACKGROUND: Characterizing the smoking patterns for different birth cohorts is
      essential for evaluating the impact of tobacco control interventions and
      predicting smoking-related mortality, but the process of estimating birth cohort
      smoking histories has received limited attention. PURPOSE: Smoking history
      summaries were estimated beginning with the 1890 birth cohort in order to provide
      fundamental parameters that can be used in studies of cigarette smoking
      intervention strategies. METHODS: U.S. National Health Interview Surveys
      conducted from 1965 to 2009 were used to obtain cross-sectional information on
      current smoking behavior. Surveys that provided additional detail on history for
      smokers including age at initiation and cessation and smoking intensity were used
      to construct smoking histories for participants up to the date of survey. After
      incorporating survival differences by smoking status, age-period-cohort models
      with constrained natural splines were used to estimate the prevalence of current,
      former, and never smokers in cohorts beginning in 1890. This approach was then
      used to obtain yearly estimates of initiation, cessation, and smoking intensity
      for the age-specific distribution for each birth cohort. These rates were
      projected forward through 2050 based on recent trends. RESULTS: This summary of
      smoking history shows clear trends by gender, cohort, and age over time. If
      current patterns persist, a slow decline in smoking prevalence is projected from
      2010 through 2040. CONCLUSIONS: A novel method of generating smoking histories
      has been applied to develop smoking histories that can be used in micro
      simulation models, and has been incorporated in the National Cancer Institute's
      Smoking History Generator. These aggregate estimates developed by age, gender,
      and cohort will provide a complete source of smoking data over time.

PMID- 24439360
TI  - Equivalent cross-relaxation rate imaging positively correlates with pathological
      grade and cell density of adipocytic tumors.
AB  - OBJECTIVE: Equivalent cross-relaxation rate imaging (ECRI) is an MRI technique
      used to evaluate qualitative changes in protein-water interactions. We aimed to
      prospectively evaluate the utility of ECRI for classification of adipocytic
      tumors. MATERIALS AND METHODS: Institutional Review Board approval was obtained
      and all patients provided informed consent. Study participants included 40
      patients with adipocytic tumors who were diagnosed with lipomas (n=22), atypical
      lipomatous tissue/well-differentiated liposarcoma (ALT/WDL; n=9), myxoid/round
      cell liposarcoma (MyL; n=6), and dedifferentiated liposarcoma (DDL; n=3), and 20
      control patients for whom subcutaneous fat in the buttock or thigh was analyzed.
      RESULTS: Mean ECR values of lipomas, ALT/WDL, and subcutaneous fat were low, and
      those of MyL and DDL were high. Mean ECR values of MyL and DDL were significantly
      higher than those of ALT/WDL. The cut-off value was 5.1%. There was a positive
      correlation between ECR value, pathological grade, and cell density in adipocytic
      tumors. CONCLUSION: The ECR value positively correlates with pathological grade
      and cell density of adipocytic tumors. Our findings suggest that ECRI is a useful
      method for preoperative evaluation of adipocytic tumors.

PMID- 24439361
TI  - Computer-aided diagnosis of breast DCE-MRI using pharmacokinetic model and 3-D
      morphology analysis.
AB  - Three-dimensional (3-D) dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) consists of a large number of images in different enhancement phases which
      are used to identify and characterize breast lesions. The purpose of this study
      was to develop a computer-assisted algorithm for tumor segmentation and
      characterization using both kinetic information and morphological features of 3-D
      breast DCE-MRI. An integrated color map created by intersecting kinetic and area
      under the curve (AUC) color maps was used to detect potential breast lesions,
      followed by the application of a region growing algorithm to segment the tumor.
      Modified fuzzy c-means clustering was used to identify the most representative
      kinetic curve of the whole segmented tumor, which was then characterized by using
      conventional curve analysis or pharmacokinetic model. The 3-D morphological
      features including shape features (compactness, margin, and ellipsoid fitting)
      and texture features (based on the grey level co-occurrence matrix) of the
      segmented tumor were obtained to characterize the lesion. One hundred and thirty
      two biopsy-proven lesions (63 benign and 69 malignant) were used to evaluate the
      performance of the proposed computer-aided system for breast MRI. Five combined
      features including rate constant (kep), volume of plasma (vp), energy (G1),
      entropy (G2), and compactness (C1), had the best performance with an accuracy of
      91.67% (121/132), sensitivity of 91.30% (63/69), specificity of 92.06% (58/63),
      and Az value of 0.9427. Combining the kinetic and morphological features of 3-D
      breast MRI is a potentially useful and robust algorithm when attempting to
      differentiate benign and malignant lesions. 

PMID- 24439362
TI  - Attitudes of detainees and prison staff towards tobacco control policy in
      Switzerland: a qualitative interview study.
AB  - PURPOSE: To explore detainees and staff's attitudes towards tobacco use, in order
      to assist prison administrators to develop an ethically acceptable tobacco
      control policy based on stakeholders' opinion. DESIGN: Qualitative study based on
      in-depth semi-structured interviews with 31 prisoners and 27 staff prior (T1) and
      after the implementation (T2) of a new smoke-free regulation (2009) in a Swiss
      male post-trial prison consisting of 120 detainees and 120 employees. RESULTS: At
      T1, smoking was allowed in common indoor rooms and most working places. Both
      groups of participants expressed the need for a more uniform and stricter
      regulation, with general opposition towards a total smoking ban. Expressed fears
      and difficulties regarding a stricter regulation were increased stress on
      detainees and strain on staff, violence, riots, loss of control on detainees, and
      changes in social life. At T2, participants expressed predominantly satisfaction.
      They reported reduction in their own tobacco use and a better protection against
      second-hand smoke. However, enforcement was incomplete. The debate was felt as
      being concentrated on regulation only, leaving aside the subject of tobacco
      reduction or cessation support. CONCLUSION: Besides an appropriate smoke-free
      regulation, further developments are necessary in order to have a comprehensive
      tobacco control policy in prisons.

PMID- 24439363
TI  - Short communication: Traits unique to genus Homo within primates at the cervical
      spine (C2-C7).
AB  - From a comparative study of 222 human and 261 nonhuman primates complete cervical
      spines, two bony variants associated to the course of the vertebral artery are
      proposed as unique to genus Homo within primates. First, the opening of the
      foramen transversarium at C2, a trait present at low frequency in humans (3 to
      5.6%). Second, the presence of a bipartite foramen transversarium in the cervical
      segment C3-C6, a trait that can be observed fully formed in human fetal
      skeletons, with a clear frequency pattern along the cervical spine
      (C3>C4>C5>C6<C7), and the expression of which does not seem to be significantly
      associated to sex or side. A clear difference is observed in the frequency of a
      third trait, the foramen transversarium at C7, present in all the human spines
      studied, practically absent in Strepsirrhini, at low frequency in Platyrrhini,
      and generalized in Catarrhini. These findings, together with previous data
      regarding absence and presence of foramina at C1, indicate a pattern of gain and
      loss of foramina in the transverse process of the cervical vertebrae for genus
      Homo. The test of a possible explanation of these differences as associated to
      anatomical changes of the cervical spine due to erect posture and bipedal
      locomotion needs further research in the morphology and function of the primate
      cervical spine.

PMID- 24439364
TI  - 40 years young.

PMID- 24439365
TI  - The shape of things to come.
AB  - Surface receptors can link binding of ligands to changes in the actin-based cell
      cytoskeleton. Chia et al. and Chen et al. provide evidence for direct binding
      between the cytoplasmic tails of receptors and the WAVE complex, a regulator of
      the actin nucleator Arp2/3 complex, which might help to explain how environmental
      signals are translated into changes in morphology and motility. 

PMID- 24439366
TI  - Myelin formation and remodeling.
AB  - Myelin is a multilayer wrapping of insulation formed by glial cells around axons
      that is essential for rapid impulse transmission, but how glial cells accomplish
      this cellular choreography has long intrigued researchers. In this issue of Cell,
      Snaidero et al., provide new insights into how myelin forms and is remodeled. 

PMID- 24439367
TI  - Bistable parvalbumin circuits pivotal for brain plasticity.
AB  - Experience shapes brain function throughout life to varying degrees. In a recent
      issue of Nature, Donato et al. identify reversible shifts in focal parvalbumin
      cell state during adult learning, placing it on a mechanistic continuum with
      developmental critical periods. A disinhibitory microcircuit controls the
      plasticity switch to modulate memory formation. 

PMID- 24439370
TI  - Neuronal control of metabolism through nutrient-dependent modulation of tracheal
      branching.
AB  - During adaptive angiogenesis, a key process in the etiology and treatment of
      cancer and obesity, the vasculature changes to meet the metabolic needs of its
      target tissues. Although the cues governing vascular remodeling are not fully
      understood, target-derived signals are generally believed to underlie this
      process. Here, we identify an alternative mechanism by characterizing the
      previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal
      system: a network of oxygen-delivering tubules developmentally akin to mammalian
      blood vessels. We find that this plasticity, particularly prominent in the
      intestine, drives--rather than responds to--metabolic change. Mechanistically, it
      is regulated by distinct populations of nutrient- and oxygen-responsive neurons
      that, through delivery of both local and systemic insulin- and VIP-like
      neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe
      a novel mechanism by which nutritional cues modulate neuronal activity to give
      rise to organ-specific, long-lasting changes in vascular architecture.

PMID- 24439368
TI  - What we talk about when we talk about fat.
AB  - There has been an upsurge of interest in the adipocyte coincident with the onset
      of the obesity epidemic and the realization that adipose tissue plays a major
      role in the regulation of metabolic function. The past few years, in particular,
      have seen significant changes in the way that we classify adipocytes and how we
      view adipose development and differentiation. We have new perspective on the
      roles played by adipocytes in a variety of homeostatic processes and on the
      mechanisms used by adipocytes to communicate with other tissues. Finally, there
      has been significant progress in understanding how these relationships are
      altered during metabolic disease and how they might be manipulated to restore
      metabolic health. 

PMID- 24439369
TI  - Reversing DNA methylation: mechanisms, genomics, and biological functions.
AB  - Methylation of cytosines in the mammalian genome represents a key epigenetic
      modification and is dynamically regulated during development. Compelling evidence
      now suggests that dynamic regulation of DNA methylation is mainly achieved
      through a cyclic enzymatic cascade comprised of cytosine methylation, iterative
      oxidation of methyl group by TET dioxygenases, and restoration of unmodified
      cytosines by either replication-dependent dilution or DNA glycosylase-initiated
      base excision repair. In this review, we discuss the mechanism and function of
      DNA demethylation in mammalian genomes, focusing particularly on how
      developmental modulation of the cytosine-modifying pathway is coupled to active
      reversal of DNA methylation in diverse biological processes. 

PMID- 24439371
TI  - An extracellular bacterial pathogen modulates host metabolism to regulate its own
      sensing and proliferation.
AB  - Successful infection depends on the ability of the pathogen to gain nutrients
      from the host. The extracellular pathogenic bacterium group A Streptococcus (GAS)
      causes a vast array of human diseases. By using the quorum-sensing sil system as
      a reporter, we found that, during adherence to host cells, GAS delivers
      streptolysin toxins, creating endoplasmic reticulum stress. This, in turn,
      increases asparagine (ASN) synthetase expression and the production of ASN. The
      released ASN is sensed by the bacteria, altering the expression of ~17% of GAS
      genes of which about one-third are dependent on the two-component system TrxSR.
      The expression of the streptolysin toxins is strongly upregulated, whereas genes
      linked to proliferation are downregulated in ASN absence. Asparaginase, a widely
      used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS
      proliferation in a mouse model of human bacteremia. These results delineate a
      pathogenic pathway and propose a therapeutic strategy against GAS infections. 

PMID- 24439373
TI  - Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal
      natural killer T cells.
AB  - Coevolution of beneficial microorganisms with the mammalian intestine
      fundamentally shapes mammalian physiology. Here, we report that the intestinal
      microbe Bacteroides fragilis modifies the homeostasis of host invariant natural
      killer T (iNKT) cells by supplementing the host's endogenous lipid antigen milieu
      with unique inhibitory sphingolipids. The process occurs early in life and
      effectively impedes iNKT cell proliferation during neonatal development.
      Consequently, total colonic iNKT cell numbers are restricted into adulthood, and
      hosts are protected against experimental iNKT cell-mediated, oxazolone-induced
      colitis. In studies with neonatal mice lacking access to bacterial sphingolipids,
      we found that treatment with B. fragilis glycosphingolipids-exemplified by an
      isolated peak (MW = 717.6) called GSL-Bf717-reduces colonic iNKT cell numbers and
      confers protection against oxazolone-induced colitis in adulthood. Our results
      suggest that the distinctive inhibitory capacity of GSL-Bf717 and similar
      molecules may prove useful in the treatment of autoimmune and allergic disorders
      in which iNKT cell activation is destructive.

PMID- 24439372
TI  - PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend
      lifespan.
AB  - Interactions between commensals and the host impact the metabolic and immune
      status of metazoans. Their deregulation is associated with age-related
      pathologies like chronic inflammation and cancer, especially in barrier
      epithelia. Maintaining a healthy commensal population by preserving innate immune
      homeostasis in such epithelia thus promises to promote health and longevity.
      Here, we show that, in the aging intestine of Drosophila, chronic activation of
      the transcription factor Foxo reduces expression of peptidoglycan recognition
      protein SC2 (PGRP-SC2), a negative regulator of IMD/Relish innate immune
      signaling, and homolog of the anti-inflammatory molecules PGLYRP1-4. This
      repression causes deregulation of Rel/NFkB activity, resulting in commensal
      dysbiosis, stem cell hyperproliferation, and epithelial dysplasia. Restoring PGRP
      SC2 expression in enterocytes of the intestinal epithelium, in turn, prevents
      dysbiosis, promotes tissue homeostasis, and extends lifespan. Our results
      highlight the importance of commensal control for lifespan of metazoans and
      identify SC-class PGRPs as longevity-promoting factors. 

PMID- 24439374
TI  - Inefficient SRP interaction with a nascent chain triggers a mRNA quality control
      pathway.
AB  - Misfolded proteins are often cytotoxic, unless cellular systems prevent their
      accumulation. Data presented here uncover a mechanism by which defects in
      secretory proteins lead to a dramatic reduction in their mRNAs and protein
      expression. When mutant signal sequences fail to bind to the signal recognition
      particle (SRP) at the ribosome exit site, the nascent chain instead contacts
      Argonaute2 (Ago2), and the mutant mRNAs are specifically degraded. Severity of
      signal sequence mutations correlated with increased proximity of Ago2 to nascent
      chain and mRNA degradation. Ago2 knockdown inhibited degradation of the mutant
      mRNA, while overexpression of Ago2 or knockdown of SRP54 promoted degradation of
      secretory protein mRNA. The results reveal a previously unappreciated general
      mechanism of translational quality control, in which specific mRNA degradation
      preemptively regulates aberrant protein production (RAPP). 

PMID- 24439375
TI  - Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events.
AB  - There are no therapies that reverse the proteotoxic misfolding events that
      underpin fatal neurodegenerative diseases, including amyotrophic lateral
      sclerosis (ALS) and Parkinson's disease (PD). Hsp104, a conserved hexameric AAA+
      protein from yeast, solubilizes disordered aggregates and amyloid but has no
      metazoan homolog and only limited activity against human neurodegenerative
      disease proteins. Here, we reprogram Hsp104 to rescue TDP-43, FUS, and alpha
      synuclein proteotoxicity by mutating single residues in helix 1, 2, or 3 of the
      middle domain or the small domain of nucleotide-binding domain 1. Potentiated
      Hsp104 variants enhance aggregate dissolution, restore proper protein
      localization, suppress proteotoxicity, and in a C. elegans PD model attenuate
      dopaminergic neurodegeneration. Potentiating mutations reconfigure how Hsp104
      subunits collaborate, desensitize Hsp104 to inhibition, obviate any requirement
      for Hsp70, and enhance ATPase, translocation, and unfoldase activity. Our work
      establishes that disease-associated aggregates and amyloid are tractable targets
      and that enhanced disaggregases can restore proteostasis and mitigate
      neurodegeneration. 

PMID- 24439376
TI  - The WAVE regulatory complex links diverse receptors to the actin cytoskeleton.
AB  - The WAVE regulatory complex (WRC) controls actin cytoskeletal dynamics throughout
      the cell by stimulating the actin-nucleating activity of the Arp2/3 complex at
      distinct membrane sites. However, the factors that recruit the WRC to specific
      locations remain poorly understood. Here, we have identified a large family of
      potential WRC ligands, consisting of ~120 diverse membrane proteins, including
      protocadherins, ROBOs, netrin receptors, neuroligins, GPCRs, and channels.
      Structural, biochemical, and cellular studies reveal that a sequence motif that
      defines these ligands binds to a highly conserved interaction surface of the WRC
      formed by the Sra and Abi subunits. Mutating this binding surface in flies
      resulted in defects in actin cytoskeletal organization and egg morphology during
      oogenesis, leading to female sterility. Our findings directly link diverse
      membrane proteins to the WRC and actin cytoskeleton and have broad physiological
      and pathological ramifications in metazoans. 

PMID- 24439377
TI  - Local F-actin network links synapse formation and axon branching.
AB  - Axonal branching and synapse formation are tightly linked developmental events
      during the establishment of synaptic circuits. Newly formed synapses promote
      branch initiation and stability. However, little is known about molecular
      mechanisms that link these two processes. Here, we show that local assembly of an
      F-actin cytoskeleton at nascent presynaptic sites initiates both synapse
      formation and axon branching. We further find that assembly of the F-actin
      network requires a direct interaction between the synaptic cell adhesion molecule
      SYG-1 and a key regulator of actin cytoskeleton, the WVE-1/WAVE regulatory
      complex (WRC). SYG-1 cytoplasmic tail binds to the WRC using a consensus WRC
      interacting receptor sequence (WIRS). WRC mutants or mutating the SYG-1 WIRS
      motif leads to loss of local F-actin, synaptic material, and axonal branches.
      Together, these data suggest that synaptic adhesion molecules, which serve as a
      necessary component for both synaptogenesis and axonal branch formation, directly
      regulate subcellular actin cytoskeletal organization. 

PMID- 24439378
TI  - Tachykinin-expressing neurons control male-specific aggressive arousal in
      Drosophila.
AB  - Males of most species are more aggressive than females, but the neural mechanisms
      underlying this dimorphism are not clear. Here, we identify a neuron and a gene
      that control the higher level of aggression characteristic of Drosophila
      melanogaster males. Males, but not females, contain a small cluster of FruM(+)
      neurons that express the neuropeptide tachykinin (Tk). Activation and silencing
      of these neurons increased and decreased, respectively, intermale aggression
      without affecting male-female courtship behavior. Mutations in both Tk and a
      candidate receptor, Takr86C, suppressed the effect of neuronal activation,
      whereas overexpression of Tk potentiated it. Tk neuron activation overcame
      reduced aggressiveness caused by eliminating a variety of sensory or contextual
      cues, suggesting that it promotes aggressive arousal or motivation.
      Tachykinin/Substance P has been implicated in aggression in mammals, including
      humans. Thus, the higher aggressiveness of Drosophila males reflects the sexually
      dimorphic expression of a neuropeptide that controls agonistic behaviors across
      phylogeny. 

PMID- 24439379
TI  - Genetic identification and separation of innate and experience-dependent
      courtship behaviors in Drosophila.
AB  - Wild-type D. melanogaster males innately possess the ability to perform a
      multistep courtship ritual to conspecific females. The potential for this
      behavior is specified by the male-specific products of the fruitless (fru(M))
      gene; males without fru(M) do not court females when held in isolation. We show
      that such fru(M) null males acquire the potential for courtship when grouped with
      other flies; they apparently learn to court flies with which they were grouped,
      irrespective of sex or species and retain this behavior for at least a week. The
      male-specific product of the doublesex gene (dsx(M)) is necessary and sufficient
      for the acquisition of the potential for such experience-dependent courtship.
      These results reveal a process that builds, via dsx(M) and social experience, the
      potential for a more flexible sexual behavior, which could be evolutionarily
      conserved as dsx-related genes that function in sexual development are found
      throughout the animal kingdom. 

PMID- 24439380
TI  - Multilevel modulation of a sensory motor circuit during C. elegans sleep and
      arousal.
AB  - Sleep is characterized by behavioral quiescence, homeostasis, increased arousal
      threshold, and rapid reversibility. Understanding how these properties are
      encoded by a neuronal circuit has been difficult, and no single molecular or
      neuronal pathway has been shown to be responsible for the regulation of sleep.
      Taking advantage of the well-mapped neuronal connections of Caenorhabditis
      elegans and the sleep-like states in this animal, we demonstrate the changed
      properties of both sensory neurons and downstream interneurons that mediate sleep
      and arousal. The ASH sensory neuron displays reduced sensitivity to stimuli in
      the sleep-like state, and the activity of the corresponding interneurons in ASH's
      motor circuit becomes asynchronous. Restoration of interneuron synchrony is
      sufficient for arousal. The multilevel circuit depression revealed provides an
      elegant strategy to promote a robust decrease in arousal while allowing for rapid
      reversibility of the sleep state. 

PMID- 24439382
TI  - Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth
      at the inner tongue.
AB  - Central nervous system myelin is a multilayered membrane sheath generated by
      oligodendrocytes for rapid impulse propagation. However, the underlying
      mechanisms of myelin wrapping have remained unclear. Using an integrative
      approach of live imaging, electron microscopy, and genetics, we show that new
      myelin membranes are incorporated adjacent to the axon at the innermost tongue.
      Simultaneously, newly formed layers extend laterally, ultimately leading to the
      formation of a set of closely apposed paranodal loops. An elaborated system of
      cytoplasmic channels within the growing myelin sheath enables membrane
      trafficking to the leading edge. Most of these channels close with ongoing
      development but can be reopened in adults by experimentally raising
      phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin
      growth. Our model can explain assembly of myelin as a multilayered structure,
      abnormal myelin outfoldings in neurological disease, and plasticity of myelin
      biogenesis observed in adult life.

PMID- 24439381
TI  - Epigenetic priming of memory updating during reconsolidation to attenuate remote
      fear memories.
AB  - Traumatic events generate some of the most enduring forms of memories. Despite
      the elevated lifetime prevalence of anxiety disorders, effective strategies to
      attenuate long-term traumatic memories are scarce. The most efficacious
      treatments to diminish recent (i.e., day-old) traumata capitalize on memory
      updating mechanisms during reconsolidation that are initiated upon memory recall.
      Here, we show that, in mice, successful reconsolidation-updating paradigms for
      recent memories fail to attenuate remote (i.e., month-old) ones. We find that,
      whereas recent memory recall induces a limited period of hippocampal
      neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone
      acetylation, such plasticity is absent for remote memories. However, by using an
      HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories
      can be persistently attenuated. This intervention epigenetically primes the
      expression of neuroplasticity-related genes, which is accompanied by higher
      metabolic, synaptic, and structural plasticity. Thus, applying HDACis during
      memory reconsolidation might constitute a treatment option for remote traumata. 

PMID- 24439383
TI  - An O2-sensitive glomus cell-stem cell synapse induces carotid body growth in
      chronic hypoxia.
AB  - Neural stem cells (NSCs) exist in germinal centers of the adult brain and in the
      carotid body (CB), an oxygen-sensing organ that grows under chronic hypoxemia.
      How stem cell lineage differentiation into mature glomus cells is coupled with
      changes in physiological demand is poorly understood. Here, we show that hypoxia
      does not affect CB NSC proliferation directly. Rather, mature glomus cells
      expressing endothelin-1, the O2-sensing elements in the CB that secrete
      neurotransmitters in response to hypoxia, establish abundant synaptic-like
      contacts with stem cells, which express endothelin receptors, and instruct their
      growth. Inhibition of glomus cell transmitter release or their selective
      destruction markedly diminishes CB cell growth during hypoxia, showing that CB
      NSCs are under the direct "synaptic" control of the mature O2-sensitive cells.
      Thus, glomus cells not only acutely activate the respiratory center but also
      induce NSC-dependent CB hypertrophy necessary for acclimatization to chronic
      hypoxemia. 

PMID- 24439384
TI  - Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a
      subcutaneous to visceral fat switch.
AB  - A clear relationship exists between visceral obesity and type 2 diabetes, whereas
      subcutaneous obesity is comparatively benign. Here, we show that adipocyte
      specific deletion of the coregulatory protein PRDM16 caused minimal effects on
      classical brown fat but markedly inhibited beige adipocyte function in
      subcutaneous fat following cold exposure or beta3-agonist treatment. These
      animals developed obesity on a high-fat diet, with severe insulin resistance and
      hepatic steatosis. They also showed altered fat distribution with markedly
      increased subcutaneous adiposity. Subcutaneous adipose tissue in mutant mice
      acquired many key properties of visceral fat, including decreased thermogenic and
      increased inflammatory gene expression and increased macrophage accumulation.
      Transplantation of subcutaneous fat into mice with diet-induced obesity showed a
      loss of metabolic benefit when tissues were derived from PRDM16 mutant animals.
      These findings indicate that PRDM16 and beige adipocytes are required for the
      "browning" of white fat and the healthful effects of subcutaneous adipose tissue.

PMID- 24439385
TI  - Regulation of ferroptotic cancer cell death by GPX4.
AB  - Ferroptosis is a form of nonapoptotic cell death for which key regulators remain
      unknown. We sought a common mediator for the lethality of 12 ferroptosis-inducing
      small molecules. We used targeted metabolomic profiling to discover that
      depletion of glutathione causes inactivation of glutathione peroxidases (GPXs) in
      response to one class of compounds and a chemoproteomics strategy to discover
      that GPX4 is directly inhibited by a second class of compounds. GPX4
      overexpression and knockdown modulated the lethality of 12 ferroptosis inducers,
      but not of 11 compounds with other lethal mechanisms. In addition, two
      representative ferroptosis inducers prevented tumor growth in xenograft mouse
      tumor models. Sensitivity profiling in 177 cancer cell lines revealed that
      diffuse large B cell lymphomas and renal cell carcinomas are particularly
      susceptible to GPX4-regulated ferroptosis. Thus, GPX4 is an essential regulator
      of ferroptotic cancer cell death. 

PMID- 24439386
TI  - The architecture of parent-of-origin effects in mice.
AB  - The number of imprinted genes in the mammalian genome is predicted to be small,
      yet we show here, in a survey of 97 traits measured in outbred mice, that most
      phenotypes display parent-of-origin effects that are partially confounded with
      family structure. To address this contradiction, using reciprocal F1 crosses, we
      investigated the effects of knocking out two nonimprinted candidate genes, Man1a2
      and H2-ab1, that reside at nonimprinted loci but that show parent-of-origin
      effects. We show that expression of multiple genes becomes dysregulated in a sex
      , tissue-, and parent-of-origin-dependent manner. We provide evidence that
      nonimprinted genes can generate parent-of-origin effects by interaction with
      imprinted loci and deduce that the importance of the number of imprinted genes is
      secondary to their interactions. We propose that this gene network effect may
      account for some of the missing heritability seen when comparing sibling-based to
      population-based studies of the phenotypic effects of genetic variants. 

PMID- 24439389
TI  - SnapShot: Lipid kinase and phosphatase reaction pathways.

PMID- 24439388
TI  - De novo inference of systems-level mechanistic models of development from live
      imaging-based phenotype analysis.
AB  - Elucidation of complex phenotypes for mechanistic insights presents a significant
      challenge in systems biology. We report a strategy to automatically infer
      mechanistic models of cell fate differentiation based on live-imaging data. We
      use cell lineage tracing and combinations of tissue-specific marker expression to
      assay progenitor cell fate and detect fate changes upon genetic perturbation.
      Based on the cellular phenotypes, we further construct a model for how fate
      differentiation progresses in progenitor cells and predict cell-specific gene
      modules and cell-to-cell signaling events that regulate the series of fate
      choices. We validate our approach in C. elegans embryogenesis by perturbing 20
      genes in over 300 embryos. The result not only recapitulates current knowledge
      but also provides insights into gene function and regulated fate choice,
      including an unexpected self-renewal. Our study provides a powerful approach for
      automated and quantitative interpretation of complex in vivo information. 

PMID- 24439392
TI  - Impact of the diagnosis and treatment of cancer on the course of inflammatory
      bowel disease.
AB  - BACKGROUND: The effects of extra-intestinal cancer on the course of inflammatory
      bowel disease (IBD) are poorly understood. AIM: To evaluate the impact of cancer
      and its management on IBD outcomes. METHODS: A total 80 IBD patients (51 Crohn's
      disease, 29 ulcerative colitis; 33 men, median age at cancer diagnosis 48yrs)
      diagnosed with extra-intestinal cancer were selected from a prospective database.
      IBD activity and therapeutic requirements (assessed year-by-year) were compared
      before and after cancer diagnosis, with a control group of patients without
      cancer matched for gender, birth date, date of IBD diagnosis and IBD phenotype.
      RESULTS: Paired comparisons of the consecutive periods before and after cancer
      diagnosis did not show significant changes in median (IQR) percentages of years
      with active disease (27% [0-50] vs. 19% [0-53]), while the proportion of patient
      years on any immunosuppressant remained stable (26% vs. 28%). Chemotherapy had no
      significant effect on IBD activity. Compared to controls, patients with cancer
      had a similar IBD activity and use of anti-TNF, but less use of immunomodulators
      (19% vs. 25%, p<0,001) and an increased rate of surgery (4% vs. 2.5%, p<0,05).
      Individual variations in IBD activity after cancer diagnosis were not
      significantly different in patients with cancer and their matched controls.
      CONCLUSION: Occurrence of extra-intestinal cancer impacts IBD therapeutic
      management, with a trend towards less use of immunomodulators and more surgery.
      In the long-term, cancer diagnoses and treatments do not modify IBD outcomes.

PMID- 24439390
TI  - Health care and patients' education in a European inflammatory bowel disease
      inception cohort: an ECCO-EpiCom study.
AB  - BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010
      in 31 centers from 14 Western and 8 Eastern European countries, covering a
      10.1million person background population. Our aim was to investigate whether
      there is a difference between Eastern and Western Europe in health care and
      education of patients with inflammatory bowel disease (IBD). METHODS: A quality
      of care (QoC) questionnaire was developed in the EpiCom group consisting of 16
      questions covering 5 items: time interval between the onset of symptoms and
      diagnosis, information, education, empathy and access to health care providers.
      RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC
      questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis.
      In Eastern Europe, significantly more patients searched out information about IBD
      themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88%
      p=0.23). In Western Europe, significantly more patients were educated by nurses
      (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to
      contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly
      between Eastern and Western Europe in all items, but satisfaction rates were high
      in both geographic regions. Because of the low awareness and the rising incidence
      of IBD, general information should be the focus of patient organizations and
      medical societies. In Western Europe IBD nurses play a very important role in
      reducing the burden of patient management.

PMID- 24439393
TI  - Systemic antifungal prophylaxis after hematopoietic stem cell transplantation: a
      meta-analysis.
AB  - BACKGROUND: Hematopoietic stem transplant recipients are subject to increased
      risk for invasive fungal infections. OBJECTIVE: This meta-analysis was undertaken
      to explore the comparative effectiveness of systemic antifungal prophylaxis in
      hematopoietic stem cell transplant recipients. METHODS: We searched PubMed and
      The Cochrane Register of Randomized Controlled Trials up to March 2013 for
      randomized studies on systemic antifungal prophylaxis after hematopoietic stem
      cell transplantation. We performed a meta-analysis on the relative effectiveness
      of systemic antifungal prophylaxis on proven or probable invasive fungal
      infections using direct and indirect effects. Relative effectiveness was reported
      as odds ratio (OR) for invasive fungal infections, causative agent, empirical
      antifungal therapy, and withdrawals due to drug adverse events. RESULTS: Twenty
      evaluable studies provided data on 4823 patients. The risk for invasive fungal
      infections while on prophylaxis was 5.1% (95% CI, 3.6-6.8%). In patients
      receiving fluconazole, risks of proven or probable invasive fungal infections (OR
      = 0.24; 95% CI, 0.11-0.50; number needed to treat [NNT] = 8), systemic
      candidiasis (OR = 0.11; 95% CI, 0.05-0.24; NNT = 7), and overall need for empiric
      antifungal treatment (OR = 0.60; 95% CI, 0.44-0.82; NNT = 8) were reduced
      compared with patients receiving placebo. Itraconazole was more effective than
      fluconazole for the prevention of aspergillosis (OR = 0.40; 95% CI, 0.19-0.83;
      NNT = 23) at the expense of more frequent withdrawals (OR = 3.01; 95% CI, 1.77
      5.13; number needed to harm = 6). Micafungin was marginally more effective than
      fluconazole for the prevention of all mold infections (OR = 0.35; 95% CI, 0.10
      1.18; NNT = 79) and invasive aspergillosis (OR = 0.19; 95% CI, 0.03-1.11; NNT =
      78) and reducing the need for empiric antifungal treatment (OR = 0.40; 95% CI,
      0.13-1.21; NNT = 8). There was a relative lack of comparisons between different
      antifungal prophylactic strategies, including the newer azoles, voriconazole and
      posaconazole, in this population. Direct effects derived from single studies
      showed marginally significant effects for voriconazole compared with fluconazole
      regarding invasive aspergillosis (OR = 0.50; 95% CI, 0.20-1.20; NNT = 35) and the
      need for empiric treatment (OR = 0.72; 95% CI, 0.50-1.06; NNT = 15). Voriconazole
      compared with itraconazole (OR = 0.59; 95% CI, 0.40-0.88; NNT = 8) and
      posaconazole compared with amphotericin B (OR = 0.28; 95% CI, 0.06-1.24, marginal
      significance; NNT = 3) were better regarding empirical antifungal treatment.
      CONCLUSIONS: Even when on antifungal therapy, invasive fungal infection will
      develop in 1 of 20 patients undergoing hematopoietic stem cell transplantation.
      There is evidence for the comparable effectiveness of different antifungal drugs
      used for prophylaxis. Fluconazole is the most widely studied agent, but
      micafungin might prove to be more effective. There is a relative paucity of
      studies for the newer azoles, although both voriconazole and posaconazole give
      proof of their comparative or higher effectiveness to fluconazole in single
      randomized studies.

PMID- 24439394
TI  - Predictors of breast feeding self-efficacy among Chinese mothers: a cross
      sectional questionnaire survey.
AB  - OBJECTIVES: to examine breast feeding self-efficacy and identify its predictors
      among expectant Chinese mothers in the antenatal period. DESIGN AND SETTING: a
      cross-sectional descriptive questionnaire survey was conducted in the antenatal
      clinics of three university hospitals in China between September and December
      2011. PARTICIPANTS: expectant mothers planning to breast feed, and who were at
      least 18 years of age, expecting a single, healthy, full-term baby, and competent
      in Mandarin (n=201). MEASUREMENTS: a socio-demographic data sheet, the Chinese
      version of the Breastfeeding Self-Efficacy Scale, and the Perceived Social
      Support Scale. FINDINGS: the expectant Chinese mothers reported moderate levels
      of breast feeding self-efficacy. Expectant mothers who had had previous
      experience in breast feeding, who had watched other mothers breast feed their
      infants, or who had made the decision to breast feed earlier reported higher
      breast feeding self-efficacy. Expectant mothers' perceived social support,
      perceived attitude of significant others, including husband, mothers, and
      friends, towards breast feeding are correlated with breast feeding self-efficacy.
      The best-fit regression analysis revealed five variables that explained 34% of
      the variance in breast feeding self-efficacy in the antenatal period: perceived
      social support, previous experience of breast feeding, previous experience of
      watching others breast feed, timing of maternal decision to breast feed, and
      perceived husband's attitude towards breast feeding. CONCLUSIONS: this study
      highlighted the importance of improving Chinese mothers' breast feeding self
      efficacy by considering the main predictors found in this study. IMPLICATIONS FOR
      PRACTICE: health care professionals could develop strategies to promote breast
      feeding self-efficacy, such as providing opportunities for expectant mothers to
      learn from others' successful experience, adopt a family-centred approach in the
      provision of breast feeding education, provide breast feeding education at the
      beginning of pregnancy or even earlier, and rally comprehensive social support
      for expectant mothers.

PMID- 24439387
TI  - Leveraging cross-species transcription factor binding site patterns: from
      diabetes risk loci to disease mechanisms.
AB  - Genome-wide association studies have revealed numerous risk loci associated with
      diverse diseases. However, identification of disease-causing variants within
      association loci remains a major challenge. Divergence in gene expression due to
      cis-regulatory variants in noncoding regions is central to disease
      susceptibility. We show that integrative computational analysis of phylogenetic
      conservation with a complexity assessment of co-occurring transcription factor
      binding sites (TFBS) can identify cis-regulatory variants and elucidate their
      mechanistic role in disease. Analysis of established type 2 diabetes risk loci
      revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1
      homeobox factor as a repressor of PPARG2 expression in adipose cells and
      demonstrate its adverse effect on lipid metabolism and systemic insulin
      sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding.
      Thus, cross-species conservation analysis at the level of co-occurring TFBS
      provides a valuable contribution to the translation of genetic association
      signals to disease-related molecular mechanisms. 

PMID- 24439395
TI  - The effect of licochalcone A on cell-aggregates ECM secretion and osteogenic
      differentiation during bone formation in metaphyseal defects in ovariectomized
      rats.
AB  - Treatment of weight-bearing bones fractures with defects is critical for patients
      with osteoporosis's rehabilitation. Although various tissue engineering methods
      were reported, the best treating strategy for tissue engineering remains to be
      identified as the limitation of enhancing the ability of the osteogenetic
      differentiation potential of seed cell is one of the cardinal issues to be
      solved. The objective of this study is to investigate the feasibility of applying
      licochalcone-A (L-A) and bone marrow mesenchymal stem cells (BMSC)-aggregate in
      bone repairing tissue engineering and further study the biological effects of L-A
      on the cell aggregate formation and osteogenic properties. 80 female Sprague
      Dawley rats underwent bilateral ovariectomy were made with a 3.5 mm femurs bone
      defects without any fixation. These rats were then randomly assigned to five
      different treatment groups: (1) empty defect (n = 16), (2) CA-LA (n = 16), (3) CA
      N (n = 16), (4) CA-L (n = 16), (5) CA-S (n = 16) and 16 female SD rats were
      treated as a control. Data showed that L-A administrated cell aggregate had a
      stronger osteogenic differentiation and mineralized formation potential than non
      administrated group both in vitro and in vivo. For in vitro study, L-A
      administrated group had a more significant expression of ECM, osteogenic
      associated maker in addition with more mineralized area and higher ALP activity
      compared with the control group. For in vivo study, 3D reconstruction of micro
      CT, HE staining and bone strength results showed that newly formed bone in groups
      administrated by L-A was significant higher than that in Sham group at 2, 4, 8
      and 12 weeks after transplantation, especially for groups which was
      systematically injected with L-A at 8 weeks. Results of our study demonstrated
      that LA could positively affect cell behavior in cell-aggregate engineering and
      could be a promising strategy in treating osteoporotic weight-bearing bones
      fractures with defects.

PMID- 24439396
TI  - Cell-selective intracellular drug delivery using doxorubicin and alpha-helical
      peptides conjugated to gold nanoparticles.
AB  - Cell penetrating peptides (CPPs), which can enter a cell through the cell
      membrane, have potential research applications in the fields of drug delivery,
      gene therapy, and cancer therapy. However, CPPs are associated with problems such
      as low cell selectivity, low cell penetrating activity, and cell toxicity. To
      overcome the disadvantages of CPPs, we constructed a drug delivery system by
      developing 25 nm gold nanospheres (GNSs) conjugated to four alpha-helical CPPs
      from our peptide library. We examined the applicability of this cell-selective
      drug delivery system by evaluating its cell-penetrating and cell death activities
      and comparing them with those activities of the TAT peptide. Using the 25 nm GNS,
      we obtained higher cell death induction activity by the anti-cancer drug
      doxorubicin compared with our previous study using a 41 nm GNS. After entering
      the cell, the peptide-conjugated 25 nm GNS accumulated around the cell nucleus.
      High cell selectivity by alpha-helical CPP sequences was also demonstrated. Our
      results indicate that these alpha-helical peptide and 25 nm GNS conjugates are
      useful elements in an efficient cell-selective drug delivery system.

PMID- 24439397
TI  - Measuring stem cell dimensionality in tissue scaffolds.
AB  - Many scaffold systems have evolved for tissue engineering and in vitro tissue
      models to provide a 3D (three-dimensional) microenvironment that enables cells to
      behave more physiologically. We hypothesized that cells would adopt morphologies
      with more 3D character during culture in scaffolds as compared to planar
      substrates. Cell shape and function are tightly linked and effects of scaffold
      niche properties on cell shape and dimensionality are important for directing
      cell function. Herein, primary human bone marrow stromal cells (hBMSCs) were
      cultured in 6 different scaffolds and on a planar control substrate. hBMSCs were
      imaged using 3D confocal microscopy, and 3D image analyses were used to assess
      hBMSC shape and dimensionality. A characteristic gyration tensor ellipsoid was
      calculated for hBMSCs in the different scaffolds which enabled hBMSC
      dimensionality to be classified based on shape. A "Dimensionality Matrix" was
      developed that showed that hBMSC shape and dimensionality were influenced by
      scaffold properties, and that scaffolds could drive hBMSCs into 1D, 2D or 3D
      shapes. In addition, the hBMSC Z-Depth was measured to determine if hBMSCs became
      less flat during culture in scaffolds. Z-Depth results showed that all 6
      scaffolds caused an increase in cell Z-Depth compared to the 2D planar substrate.
      These results demonstrate that hBMSCs take on morphologies with greater 3D
      character in scaffolds than on a planar substrate and that scaffold properties
      can be adjusted to modify cell dimensionality. In addition, biomaterialists can
      use this measurement approach to assess and compare scaffold design modifications
      as they strive to create optimal cell niches that provide a 3D microenvironment. 

PMID- 24439398
TI  - Biomembrane-mimicking lipid bilayer system as a mechanically tunable cell
      substrate.
AB  - Cell behavior such as cell adhesion, spreading, and contraction critically
      depends on the elastic properties of the extracellular matrix. It is not known,
      however, how cells respond to viscoelastic or plastic material properties that
      more closely resemble the mechanical environment cells encounter in the body. In
      this report, we employ viscoelastic and plastic biomembrane-mimicking cell
      substrates. The compliance of the substrates can be tuned by increasing the
      number of polymer-tethered bilayers. This leaves the density and conformation of
      adhesive ligands on the top bilayer unaltered. We then observe the response of
      fibroblasts to these property changes. For comparison, we also study the cells on
      soft polyacrylamide and hard glass surfaces. Cell morphology, motility, cell
      stiffness, contractile forces and adhesive contact size all decrease on more
      compliant matrices but are less sensitive to changes in matrix dissipative
      properties. These data suggest that cells are able to feel and respond
      predominantly to the effective matrix compliance, which arises as a combination
      of substrate and adhesive ligand mechanical properties. 

PMID- 24439399
TI  - Reduction of ectopic bone growth in critically-sized rat mandible defects by
      delivery of rhBMP-2 from kerateine biomaterials.
AB  - Absorbable collagen sponges (ACS) are used clinically as carriers of recombinant
      human bone morphogenetic protein 2 (rhBMP-2) to promote bone regeneration. ACS
      exhibit ectopic bone growth due to delivery of supraphysiological levels of rhBMP
      2, which is particularly problematic in craniofacial bone injuries for both
      functional and esthetic reasons. We hypothesized that hydrogels from the reduced
      form of keratin proteins (kerateine) would serve as a suitable alternative to ACS
      carriers of rhBMP-2. The rationale for this hypothesis is that keratin
      biomaterials degrade slowly in vivo, have modifiable material properties, and
      have demonstrated capacity to deliver therapeutic agents. We investigated
      kerateine hydrogels and freeze-dried scaffolds as rhBMP-2 carriers in a
      critically-sized rat mandibular defect model. ACS, kerateine hydrogels, and
      kerateine scaffolds loaded with rhBMP-2 achieved bridging in animals by 8 weeks
      as indicated by micro-computed tomography. Kerateine scaffolds achieved
      statistically increased bone mineral density compared to ACS and kerateine
      hydrogels, with levels reaching those of native bone. Importantly, both kerateine
      hydrogels and kerateine scaffolds had significantly less ectopic bone growth than
      ACS sponges at both 8 and 16 weeks post-operatively. These studies demonstrate
      the suitability of keratins as rhBMP-2 carriers due to equal regenerative
      capacity with reduced ectopic growth compared to ACS. 

PMID- 24439400
TI  - Geometric control of capillary architecture via cell-matrix mechanical
      interactions.
AB  - Capillary morphogenesis is a multistage, multicellular activity that plays a
      pivotal role in various developmental and pathological situations. In-depth
      understanding of the regulatory mechanism along with the capability of
      controlling the morphogenic process will have direct implications on tissue
      engineering and therapeutic angiogenesis. Extensive research has been devoted to
      elucidate the biochemical factors that regulate capillary morphogenesis. The
      roles of geometric confinement and cell-matrix mechanical interactions on the
      capillary architecture, nevertheless, remain largely unknown. Here, we show
      geometric control of endothelial network topology by creating physical
      confinements with microfabricated fences and wells. Decreasing the thickness of
      the matrix also results in comparable modulation of the network architecture,
      supporting the boundary effect is mediated mechanically. The regulatory role of
      cell-matrix mechanical interaction on the network topology is further supported
      by alternating the matrix stiffness by a cell-inert PEG-dextran hydrogel.
      Furthermore, reducing the cell traction force with a Rho-associated protein
      kinase inhibitor diminishes the boundary effect. Computational biomechanical
      analysis delineates the relationship between geometric confinement and cell
      matrix mechanical interaction. Collectively, these results reveal a
      mechanoregulation scheme of endothelial cells to regulate the capillary network
      architecture via cell-matrix mechanical interactions. 

PMID- 24439401
TI  - Differences in morphogenesis of 3D cultured primary human osteoblasts under
      static and microfluidic growth conditions.
AB  - As information on osteoblast mechanosensitivity response to biomechanical cues in
      three-dimensional (3D) in vitro microenvironments is sparse, the present study
      compared morphogenesis of primary human alveolar bone osteoblasts (PHABO) under
      microchip-based 3D-static conditions, and 3D-fluid flow-mediated biomechanical
      stimulation in perfusion bioreactors. Discrimination of the respective
      microenvironment by differential morphogenesis was evident from fluid flow
      induced PHABO reorganization into rotund bony microtissue, comprising more
      densely packed multicellular 3D-aggregates, while viability of microtissues was
      flow rate dependent. Time-lapse microscopy and simple modeling of biomechanical
      conditions revealed that physiologically relevant fluid flow-mediated PHABO
      stimulation was associated with formation of mulberry-like PHABO aggregates
      within the first 24 h. Differential extracellular matrix deposition patterns and
      gene expression modulation in PHABO aggregates at day 7 further indicates
      progressive osteoblast differentiation exclusively in perfusion culture-developed
      bony microtissues. The results of our study strongly suggest PHABO morphogenesis
      as discriminator of microenvironmental growth conditions, which in case of the
      microfluidic 3D microchip-bioreactor are substantiated by triggering in vitro
      bone microtissue formation concomitant with progressive osteoblastic
      differentiation. Such microtissue outcomes provide unique insight for
      mechanobiological studies in response to biomechanical fluid flow cues, and
      clinically appear promising for in vitro PHABO preconditioning, enabling
      innovative bone augmentation procedures.

PMID- 24439402
TI  - Curcumin nanoformulations: a review of pharmaceutical properties and preclinical
      studies and clinical data related to cancer treatment.
AB  - Curcumin, a natural yellow phenolic compound, is present in many kinds of herbs,
      particularly in Curcuma longa Linn. (turmeric). It is a natural antioxidant and
      has shown many pharmacological activities such as anti-inflammatory, anti
      microbial, anti-cancer, and anti-Alzheimer in both preclinical and clinical
      studies. Moreover, curcumin has hepatoprotective, nephroprotective,
      cardioprotective, neuroprotective, hypoglycemic, antirheumatic, and antidiabetic
      activities and it also suppresses thrombosis and protects against myocardial
      infarction. Particularly, curcumin has demonstrated efficacy as an anticancer
      agent, but a limiting factor is its extremely low aqueous solubility which
      hampers its use as therapeutic agent. Therefore, many technologies have been
      developed and applied to overcome this limitation. In this review, we summarize
      the recent works on the design and development of nano-sized delivery systems for
      curcumin, including liposomes, polymeric nanoparticles and micelles, conjugates,
      peptide carriers, cyclodextrins, solid dispersions, lipid nanoparticles and
      emulsions. Efficacy studies of curcumin nanoformulations using cancer cell lines
      and in vivo models as well as up-to-date human clinical trials are also
      discussed.

PMID- 24439403
TI  - The effect of side-chain functionality and hydrophobicity on the gene delivery
      capabilities of cationic helical polypeptides.
AB  - The rational design of effective and safe non-viral gene vectors is largely
      dependent on the understanding of the structure-property relationship. We herein
      report the design of a new series of cationic, alpha-helical polypeptides with
      different side charged groups (amine and guanidine) and hydrophobicity, and
      mechanistically unraveled the effect of polypeptide structure on the gene
      delivery capability. Guanidine-containing polypeptides displayed superior
      membrane activities to their amine-containing analogues via the pore formation
      mechanism, and thus possessed notably higher transfection efficiencies.
      Elongating the hydrophobic side chain also potentiated the membrane activities of
      the polypeptides, while at the meantime caused higher cytotoxicities. Upon an
      optimal balance between membrane activity and cytotoxicity, maximal transfection
      efficiency was achieved which outperformed commercial reagent LipofectamineTM
      2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into
      the rational design of non-viral gene delivery vectors, and the best-performing
      materials identified also serve as a promising addition to the existing systems. 

PMID- 24439404
TI  - Long-term biodistribution in vivo and toxicity of radioactive/magnetic
      hydroxyapatite nanorods.
AB  - Although nanoscale hydroxyapatite [Ca10(PO4)6(OH)2; HA] has been widely
      investigated as a carrier in the delivery of drugs, genes, or siRNA, the in vivo
      toxicity of nanoscale HA is not clear and the long-term dynamic distribution in
      vivo has not hitherto been visualized. In this work, gadolinium-doped HA nanorods
      (HA:Gd) with an r1 value of 5.49 s(-1) (mm)(-1) have been prepared by a
      hydrothermal method. Samarium-153 ((153)Sm) was then effectively post-labeled
      onto the HA:Gd ((153)Sm-HA:Gd) with a labeling rate of ~100% and a radio-labeling
      stability in vitro of ~100% over 48 h. The product could serve as a new dual
      modality probe for SPECT and MR imaging in vivo. By means of SPECT and MRI, the
      HA:Gd nanorods were found to be quickly taken up by the mononuclear phagocyte
      system, especially the liver and spleen. The nanorods in the liver and lung
      tended to be eliminated within 24 h, but nanorods in the spleen behaved
      differently and proved difficult to excrete. In vitro studies by cell
      transmission electron microscopy (TEM) and methyl thiazolyl tetrazolium (MTT)
      assay showed good biocompatibility of the HA:Gd nanorods with HeLa cells, even at
      a high concentration. The indicators of body weight, histology, and serology
      demonstrated that the HA:Gd nanorods exhibited excellent biocompatibility in vivo
      for at least 61 days. Therefore, (153)Sm-HA:Gd nanorods with excellent
      relaxivity, gamma-emission, and biosafety offer clear advantages and potential
      for bioapplications.

PMID- 24439405
TI  - Cell encapsulation via microtechnologies.
AB  - The encapsulation of living cells in a variety of soft polymers or hydrogels is
      important, particularly, for the rehabilitation of functional tissues capable of
      repairing or replacing damaged organs. Cellular encapsulation segregates cells
      from the surrounding tissue to protect the implanted cell from the recipient's
      immune system after transplantation. Diverse hydrogel membranes have been
      popularly used as encapsulating materials and permit the diffusion of gas,
      nutrients, wastes and therapeutic products smoothly. This review describes a
      variety of methods that have been developed to achieve cellular encapsulation
      using microscale platform. Microtechnologies have been adopted to precisely
      control the encapsulated cell number, size and shape of a cell-laden polymer
      structure. We provide a brief overview of recent microtechnology-based cell
      encapsulation methods, with a detailed description of the relevant processes.
      Finally, we discuss the current challenges and future directions likely to be
      taken by cell microencapsulation approaches toward tissue engineering and cell
      therapy applications. 

PMID- 24439406
TI  - Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles.
AB  - Severe hypoxemia refractory to pulmonary mechanical ventilation remains life
      threatening in critically ill patients. Peritoneal ventilation has long been
      desired for extrapulmonary oxygenation owing to easy access of the peritoneal
      cavity for catheterization and the relative safety compared to an extracorporeal
      circuit. Unfortunately, prior attempts involving direct oxygen ventilation or
      aqueous perfusates of fluorocarbons or hemoglobin carriers have failed, leading
      many researchers to abandon the method. We attribute these prior failures to
      limited mass transfer of oxygen to the peritoneum and have designed an oxygen
      formulation that overcomes this limitation. Using phospholipid-coated oxygen
      microbubbles (OMBs), we demonstrate 100% survival for rats experiencing acute
      lung trauma to at least 2 h. In contrast, all untreated rats and rats treated
      with peritoneal oxygenated saline died within 30 min. For rats treated with OMBs,
      hemoglobin saturation and heart rate were at normal levels over the 2-h
      timeframe. Peritoneal oxygenation with OMBs was therefore shown to be safe and
      effective, and the method requires less equipment and technical expertise than
      initiating and maintaining an extracorporeal circuit. Further translation of
      peritoneal oxygenation with OMBs may provide therapy for acute respiratory
      distress syndrome arising from trauma, sepsis, pneumonia, aspiration, burns and
      other pulmonary diseases.

PMID- 24439407
TI  - Enhancement of retinal pigment epithelial culture characteristics and subretinal
      space tolerance of scaffolds with 200 nm fiber topography.
AB  - Tissue engineered retinal pigment epithelial (RPE) transplantation is a promising
      cell-based therapy for age-related macular degeneration. The aim of this work is
      to develop a supportive scaffold with a favorable topography to aid functional
      RPE monolayer maintenance while being tolerated underneath the retina. To this
      end, films and electrospun substrates with fiber diameters ranging from 200 to
      1000 nm were made of polyethylene terephthalate or poly(L-lactide-co-epsilon
      caprolactone), and then tested using human fetal RPE cells in vitro and
      transplanted subretinally in rabbits. The results indicated that RPE on both 200
      nm fiber variants showed the highest cell densities, adherent monolayers achieved
      deeper pigmentation, and more uniform hexagonal tight junctions. Facile
      subretinal implantation of flat 200 nm fiber membranes was achieved by
      electrospinning them onto a porous rigid-elastic carrier. Spectral-domain optical
      coherence tomography showed a reattached, slightly thinned retina overlying the
      implants over 2 weeks observation. Histology demonstrated native RPE variably
      migrated onto the nanofibers, and a reactive gliosis with some photoreceptor
      degeneration. In conclusion, scaffolds with 200 nm fiber topography enhanced RPE
      culture, showed subretinal biocompatibility, and should thus be considered for
      future cell-based therapies in blinding retinal diseases.

PMID- 24439408
TI  - Molecular and structural patterns of bone regeneration in surgically created
      defects containing bone substitutes.
AB  - Several biomaterials have been introduced for bone augmentation. However,
      information is lacking about the mechanisms of bone regeneration and/or
      integration of these materials in the recipient bone. This study aimed to
      determine the molecular and structural events in bone defects after augmentation
      with synthetic tetrapod-shaped calcium phosphate (Tetrabone; TetraB) compared
      with natural deproteinized bovine bone (DBB). Defects were created in the
      epiphyses of rat femurs and filled with TetraB or DBB or left empty (Sham). After
      3, 6, 14 and 28 d, samples were harvested for histology, histomorphometry,
      ultrastructure and gene expression analyses. At 3 d, higher expressions of bone
      formation (ALP and OC) and remodeling (CatK) genes were detected in TetraB
      compared with DBB and Sham. Downregulation of bone remodeling genes (TRAP and
      CatK) was detected in DBB as compared to Sham after 14 d. Histomorphometry at 6
      and 14 d demonstrated greater bone contact with the granules in TetraB. At 28 d,
      a larger bone area per defect was found in TetraB. The present experiments show
      that a synthetic substitute, consisting of alpha-tricalcium and octacalcium
      phosphates, induces early osteogenic and osteoclastic activities and promotes
      bone formation in trabecular bone defects.

PMID- 24439409
TI  - BMP-9 as a potent brown adipogenic inducer with anti-obesity capacity.
AB  - BMP-9, whose expression is highest in liver cells, has been demonstrated to
      regulate expression of enzymes involved in glucose homeostasis. However, the
      underlying mechanism of this effect has yet to be elucidated. We observed that
      MB109, a recombinant BMP-9 derivative, enhanced brown adipogenesis of human
      adipose tissue derived stem cells. With this observation of the cell culture
      system, we hypothesized that MB109 may be able to improve glucose metabolism by
      regulating expression of brown adipogenic genes. Systemic intraperitoneal
      injection of MB109 (200 MUg/kg/wk) suppressed weight gaining of high fat diet
      induced obese mice by reducing sizes of white adipocytes and decreased 16 h
      fasting blood glucose levels without changing food consumption or apparent
      behavioral performances. MB109 induced expression of brown adipogenic genes in
      the subcutaneous but not in the visceral fat tissues from the mice fed with high
      fat diet. In addition, systematic injection of MB109 enhanced fatty acid synthase
      expression in the liver of obese mice, which may help attenuate an obesity
      associated increase of blood glucose levels. Our results demonstrate a role of
      BMP-9 in brown adipogenesis and suppressing pathophysiology of high fat diet
      induced obesity, presumably through the activin receptor like kinase 1 signaling
      pathway.

PMID- 24439411
TI  - The potential of pH-responsive PEG-hyperbranched polyacylhydrazone micelles for
      cancer therapy.
AB  - pH-responsive hyperbranched polymers have attracted much attention due to their
      unique properties for tumor-targeted drug delivery. In this study, we describe a
      pH-responsive drug carrier, poly (ethylene glycol) (PEG)-hyperbranched
      polyacylhydrazone (HPAH), which can form nanoscale micelles to be used as anti
      cancer drug carriers with pH-controlled drug release. The molecular structure of
      PEG-HPAH was confirmed by nuclear magnetic resonance spectroscopy (NMR) and
      Fourier transform infrared spectroscopy (FTIR). The drug-loaded micelles with a
      diameter of approximately 190 nm, were prepared using a dialysis method against
      PBS with a pH of 8.0. The drug-loaded micelles showed the desired pH-dependent
      drug release properties. The drug release levels were low at neutral and alkaline
      pH, but increased significantly with a decrease in the pH of the medium.
      Intracellular uptake results indicated that the PEG-HPAH-drug micelles could
      efficiently deliver chemotherapeutic drugs into the cells. In addition, it was
      found that the subcellular localization of the drug-loaded micelles was different
      from that of free drugs, in which the drug-loaded micelles were mainly in the
      cytoplasm. The docetaxel (DTX)-loaded PEG-HPAH micelles presented a high
      cytotoxic activity against tumor cells in vitro. When combined with the
      administration of glucose, the PEG-HPAH-DTX micelles exhibited a superior anti
      tumor efficacy and a lower systemic toxicity in vivo. The biodistribution profile
      showed increased accumulated drug levels in tumor tissue and plasma in micelles
      treated group. The results indicate that the nanoscale PEG-HPAH-DTX micelles may
      serve as a selective tumor-targeting drug delivery system.

PMID- 24439410
TI  - Creating polymer hydrogel microfibres with internal alignment via electrical and
      mechanical stretching.
AB  - Hydrogels have been widely used for 3-dimensional (3D) cell culture and tissue
      regeneration due to their tunable biochemical and physicochemical properties as
      well as their high water content, which resembles the aqueous microenvironment of
      the natural extracellular matrix. While many properties of natural hydrogel
      matrices are modifiable, their intrinsic isotropic structure limits the control
      over cellular organization, which is critical to restore tissue function. Here we
      report a generic approach to incorporate alignment topography inside the hydrogel
      matrix using a combination of electrical and mechanical stretching. Hydrogel
      fibres with uniaxial alignment were prepared from aqueous solutions of natural
      polymers such as alginate, fibrin, gelatin, and hyaluronic acid under ambient
      conditions. The unique internal alignment feature drastically enhances the
      mechanical properties of the hydrogel microfibres. Furthermore, the facile,
      organic solvent-free processing conditions are amenable to the incorporation of
      live cells within the hydrogel fibre or on the fibre surface; both approaches
      effectively induce cellular alignment. This work demonstrates a versatile and
      scalable strategy to create aligned hydrogel microfibres from various natural
      polymers. 

PMID- 24439412
TI  - Modulation of monocytic leukemia cell function and survival by high gradient
      magnetic fields and mathematical modeling studies.
AB  - The influence of spatially modulated high gradient magnetic fields on cellular
      functions of human THP-1 leukemia cells is studied. We demonstrate that arrays of
      high-gradient micrometer-sized magnets induce i) cell swelling, ii) prolonged
      increased ROS production, and iii) inhibit cell proliferation, and iv) elicit
      apoptosis of THP-1 monocytic leukemia cells in the absence of chemical or
      biological agents. Mathematical modeling indicates that mechanical stress exerted
      on the cells by high magnetic gradient forces is responsible for triggering cell
      swelling and formation of reactive oxygen species followed by apoptosis. We
      discuss physical aspects of controlling cell functions by focused magnetic
      gradient forces, i.e. by a noninvasive and nondestructive physical approach. 

PMID- 24439413
TI  - Multifunctional cationic polymer decorated and drug intercalated layered silicate
      (NLS) for early gastric cancer prevention.
AB  - A multifunctional compound that can prevent early gastric cancer is produced by
      intercalating 3.20% and 1.64% of 5-FU into the interlayer of montmorillonite
      (MMT) and attapulgite (At), respectively. A low molecular weight cationic
      polymer, polyethylenimine (PEI1200), is incorporated into the surface of the 5-FU
      MMT and 5-FU-At to form the multifunctional layered silicate (NLS). The chemical
      structure and surface morphology of the NLS are characterized and the model drug
      of 5-FU is intercalated into the MMT and At. The cell viability determined by the
      MTT assay on the BGC-823 cell lines show that over 80% of the cells are live
      under the experimental conditions. The PEI-5-FU-MMT and PEI-5-FU-At can carry the
      report gene to the BGC-823 and COS-7 cell lines efficiently. Western blotting
      assay shows that the pTrail protein of the BGC-823 cell lines treated with PEI-5
      FU-MMT/pTrail and PEI-5-FU-At/pTrail is up-regulated, whereas the cFLIP protein
      is down-regulated at 48 h compared to free 5-FU, PEI1200, MMT, and At, providing
      evidence that the NLS can increase the sensitivity of pTrail gene and improve the
      effects of pTrail gene therapy. Moreover, the Helicobacter pylori (HP) bacteria
      are adsorbed and immobilized efficiently on the surface of the NLS according to
      the LIVE/DEAD((r)) BacLightTM Bacterial Viability Kit in the confocal
      fluorescence analysis. The histochemical analyses provide evidence that
      NLS/pTrail can prevent early gastric mucosa effectively.

PMID- 24439414
TI  - Enhanced reseeding of decellularized rodent lungs with mouse embryonic stem
      cells.
AB  - Repopulation of decellularized lung scaffolds (DLS) is limited due to alterations
      in the repertoire and ratios of the residual extracellular matrix (ECM) proteins,
      characterized by e.g., the retention of type I collagen and loss of
      glycoproteins. We hypothesized that pre-treatment of decellularized matrices with
      defined ECM proteins, which match the repertoire of integrin receptors expressed
      by the cells to be seeded (e.g., embryonic stem cells) can increase the efficacy
      of the reseeding process. To test this hypothesis, we first determined the
      integrin receptors profile of mouse embryonic stem cells (mESCs). Mouse ESCs
      express alpha3, alpha5, alpha6, alpha9 and beta1, but not alpha1, alpha2 and
      alpha4 integrin subunits, as established by Western blotting and adhesion to
      laminin and fibronectin, but not to collagens type I and IV. Reseeding of DLS
      with mESCs was inefficient (6.9 +/- 0.5%), but was significantly enhanced (2.3 +/
      0.1 fold) by pre-treating the scaffolds with media conditioned by A549 human
      lung adenocarcinoma cells, which we found to contain ~5 MUg/ml laminin.
      Furthermore, pre-treatment with A549-conditioned media resulted in a
      significantly more uniform distribution of the seeded mESCs throughout the
      engineered organ as compared to untreated DLS. Our study may advance whole lung
      engineering by stressing the importance of matching the integrin receptor
      repertoire of the seeded cells and the cell binding motifs of DLS.

PMID- 24439415
TI  - The reduction of anti-cancer drug antagonism by the spatial protection of drugs
      with PLA-TPGS nanoparticles.
AB  - Docetaxel (DCL) and tamoxifen (TAM) individually are potent drugs in the fight
      against breast cancer. However when used in combination, they become antagonistic
      because of differential metabolism of both drugs. We reasoned that by spatially
      protecting them from metabolizing enzymes with poly (lactide)-D-alpha-tocopheryl
      polyethylene glycol succinate (PLA-TPGS) nanoparticles (NPs), we might reduce
      this drug antagonism. We now report that the drug antagonism between DCL and TAM
      in MCF7 cell line, was significantly reduced when co-delivered in PLA-TPGS NPs.
      In addition, this effect of NPs attenuated at high drug concentrations. To
      investigate the role of NPs in the reduction of drug antagonism, we quantified
      cellular uptake of the fluorescent model drug coumarin 6 (C6) encapsulated in a
      rigorous permutation of drugs-nanoparticles ratios. NPs carrying C6 exhibited
      enhanced cellular uptake over their free C6 counterparts at correspondingly low
      drug concentrations. This led us to conclude that the reduction of drug
      antagonism by NPs is correlated to cellular uptake and being in NPs therefore
      protects both drugs until they are released intracellular for therapeutic anti
      cancer effect.

PMID- 24439416
TI  - Long-acting beneficial effect of percutaneously intramyocardially delivered
      secretome of apoptotic peripheral blood cells on porcine chronic ischemic left
      ventricular dysfunction.
AB  - The quantity of cells with paracrine effects for use in myocardial regeneration
      therapy is limited. This study investigated the effects of catheter-based
      endomyocardial delivery of secretome of 2.5 * 10(9) apoptotic peripheral blood
      mononuclear cells (APOSEC) on porcine chronic post-myocardial infarction (MI)
      left ventricular (LV) dysfunction and on gene expression. Closed-chest reperfused
      MI was induced in pigs by 90-min occlusion followed by reperfusion of the mid-LAD
      (day 0). At day 30, animals were randomized to receive porcine APOSEC (n = 8) or
      medium solution (control; n = 8) injected intramyocardially into the MI border
      zone using 3D NOGA guidance. At day 60, cardiac MRI with late enhancement and
      diagnostic NOGA (myocardial viability) were performed. Gene expression profiling
      of the infarct core, border zone, and normal myocardium was performed using
      microarray analysis and confirmed by quantitative real-time PCR. Injection of
      APOSEC significantly decreased infarct size (p < 0.05) and improved cardiac index
      and myocardial viability compared to controls. A trend towards higher LV ejection
      fraction was observed in APOSEC vs. controls (45.4 +/- 5.9% vs. 37.4 +/- 8.9%, p
      = 0.052). Transcriptome analysis revealed significant downregulation of caspase
      1, tumor necrosis factor and other inflammatory genes in APOSEC-affected areas.
      rtPCR showed higher expression of myogenic factor Mefc2 (p < 0.05) and
      downregulated caspase genes (p < 0.05) in APOSEC-treated pigs. In conclusion,
      overexpression of MEF2c and repression of caspase was related to decreased
      infarct size and improved cardiac function in secretome-treated animals. Altered
      gene expression 1-month post-APOSEC treatment proved the long-acting effects of
      cell-free therapy with paracrine factors.

PMID- 24439417
TI  - Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD
      moiety for systemic treatment of pancreatic tumors.
AB  - Adequate retention in systemic circulation is the preliminary requirement for
      systemic gene delivery to afford high bioavailability into the targeted site.
      Polyplex micelle formulated through self-assembly of oppositely-charged
      poly(ethylene glycol) (PEG)-polycation block copolymer and plasmid DNA has gained
      tempting perspective upon its advantageous core-shell architecture, where outer
      hydrophilic PEG shell offers superior stealth behaviors. Aiming to promote these
      potential characters toward systemic applications, we strategically introduced
      hydrophobic cholesteryl moiety at the omega-terminus of block copolymer,
      anticipating to promote not only the stability of polyplex structure but also the
      tethered PEG crowdedness. Moreover, Mw of PEG in the PEGylated polyplex micelle
      was elongated up to 20 kDa for expecting further enhancement in PEG crowdedness.
      Furthermore, cyclic RGD peptide as ligand molecule to integrin receptors was
      installed at the distal end of PEG in order for facilitating targeted delivery to
      the tumor site as well as promoting cellular uptake and intracellular trafficking
      behaviors. Thus constructed cRGD conjugated polyplex micelle with the elevated
      PEG shielding was challenged to a modeled intractable pancreatic cancer in mice,
      achieving potent tumor growth suppression by efficient gene expression of
      antiangiogenic protein (sFlt-1) at the tumor site.

PMID- 24439418
TI  - The anti-tumor efficacy of curcumin when delivered by size/charge-changing
      multistage polymeric micelles based on amphiphilic poly(beta-amino ester)
      derivates.
AB  - Modifying positive surface charge and reducing bulk size of nanoparticles has
      been proven beneficial to cancer cellular delivery, but meanwhile results in fast
      clearance and unspecific distribution in body after intravenous injection. How to
      balance these problems is still a challenge to construct an ideal nano-scaled
      drug delivery system in cancer treatment. Herein, we developed a multistage drug
      delivery system to enhance anticancer efficacy of curcumin (CUR), which could
      intelligently alter its size and surface charge after long-circulation and
      extravasation from leaky blood vessels at tumor sites. This micellar system was
      constructed by amphiphilic and pH-sensitive methoxy poly(ethylene glycol)
      poly(lactide)-poly(beta-amino ester) (MPEG-PLA-PAE) copolymers. As compared with
      MPEG-PLA micelles, MPEG-PLA-PAE micelles displayed several advantageous
      characteristics for drug delivery and treatment. We found that CUR-loaded MPEG
      PLA-PAE micelles remained stable in murine plasma at 37  degrees C even with high
      drug loading. More interestingly, when the media pH decreased from 7.4 to 5.5,
      the micelles shrank from 171.0 nm to 22.6 nm and their surface charge increased
      to 24.8 mV meanwhile, which resulted in the significantly improved cell uptake of
      CUR by human breast cancer MCF-7 cells. Using indocyanine green (ICG) as a
      fluorescence probe, it was observed that MPEG-PLA-PAE micelles experienced longer
      circulation than MPEG-PLA micelles followed by accumulation at tumors with
      stronger fluorescence intensity. Consequently, MPEG-PLA-PAE micelles achieved
      enhanced cancer growth inhibition of 65.6% in vivo. All these findings
      demonstrated the potential of size/charge-changing MPEG-PLA-PAE micelles as a
      promising drug delivery system for tumor-targeted therapy.

PMID- 24439419
TI  - Performance of beta-tricalcium phosphate granules and putty, bone grafting
      materials after bilateral sinus floor augmentation in humans.
AB  - Sinus floor augmentation (SFA) using bone grafting materials, and in particular
      calcium phosphates (CaP), is a well-established pre-implantology procedure. The
      use of CaP simplifies SFA procedures. beta-tricalcium phosphate (beta-TCP) is
      amply used for SFA. This study evaluated the clinical and osteogenic performance
      of beta-TCP granules (TCP-G) and a beta-TCP putty (TCP-P) bone graft material.
      TCP-P consisted of TCP-G in a hyaluronic acid (HyA) carrier. Bone formation,
      volume stability and osteogenic marker expression after bilateral SFA in patients
      was assessed. Eight patients were selected for a split-mouth design. Biopsies
      obtained six months after SFA, were processed for immunohistochemical analysis of
      collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone
      sialoprotein (BSP). Histomorphometric analysis determined bone, grafting material
      and marrow space percentages. Cone-beam computed tomography was used to calculate
      the graft volume and its stability. Both materials allowed excellent bone
      regeneration and volume stability. TCP-P displayed better surgical handling
      properties, greater bone formation, higher expression of Col I, ALP, OC and BSP;
      as well as significantly lower grafting volume reduction values. HyA had no
      adverse effect on TCP-P performance. Due to its clinical and osteogenic
      performance, TCP-P can be regarded as excellent bone grafting material for SFA. 

PMID- 24439420
TI  - Pharmacokinetic parameters for assessing bioequivalence of epinephrine
      autoinjectors.

PMID- 24439421
TI  - History of allergic diseases and lung cancer risk.
AB  - BACKGROUND: The exact nature and direction of the association between a history
      of allergic diseases and lung cancer risk remain controversial. OBJECTIVE: To
      examine the association between self-reported history of allergic diseases and
      lung cancer using data from a population-based case-control study conducted in
      the Montreal metropolitan area (1996-2002). METHODS: The study is based on
      interview data collected from 1,169 incident lung cancer cases and 1,486
      controls. Separate logistic regression models were used to estimate the relative
      risk of lung cancer, using odds ratios (ORs) and 95% confidence intervals (CIs),
      in subjects with vs without asthma, eczema, or hay fever after adjustment for
      several sociodemographic and lifestyle factors, including smoking. RESULTS: For
      asthma, the OR was 0.90 (95% CI 0.65-1.24), which decreased to 0.76 (95% CI 0.54
      1.08) for subjects whose onset was more than 2 years before lung cancer diagnosis
      or interview and then to 0.64 (95% CI 0.44-0.93) when restricted to subjects who
      reported using medication for their asthma. For eczema, the point estimate was
      0.73 (95% CI 0.48-1.12), which decreased to 0.63 (95% CI 0.38-1.07) when
      considering eczema only in those who reported medication use. Hay fever showed
      the strongest inverse association with lung cancer (OR 0.37, 95% CI 0.24-0.59).
      CONCLUSION: All 3 allergic diseases examined were inversely associated with lung
      cancer, although the strength of the protective effect varied. History of
      allergic diseases seems to have a protective role in lung cancer incidence, after
      consideration of potential confounders, including lifetime smoking history.

PMID- 24439422
TI  - Maternal hemoglobin levels during pregnancy and asthma in childhood: the
      Generation R Study.

PMID- 24439423
TI  - Anti-Ca/anti-ARHGAP26 antibodies associated with cerebellar atrophy and cognitive
      decline.
AB  - Recently, we identified a novel Purkinje cell-specific autoantibody (termed anti
      Ca) targeting rhoGTPase-activating-protein-26 (ARHGAP26) in a patient with
      cerebellar ataxia. Here we describe a new case of anti-Ca/ARHGAP26 antibody
      positive cerebellar ataxia. Cerebellar ataxia was associated with signs of
      possible limbic encephalitis in this case. The 24-year-old man presented with
      subacute pancerebellar ataxia, flattened affect, and cognitive decline.
      Neuropsychological testing revealed working memory deficits, compromised verbal
      learning and recall, attention deficits, slowed information processing,
      interference difficulty, and reduced spatial recognition. MRI showed severe
      pancerebellar atrophy. Serological examinations revealed high-titre anti-Ca/anti
      ARHGAP26 antibodies. The antibodies belonged to the IgG1 subclass and were
      produced intrathecally. This case further corroborates the association of anti-Ca
      antibodies with cerebellar ataxia, expands the clinical spectrum, and highlights
      the necessity of antigen-specific diagnostic testing in immune-mediated
      cerebellar ataxia. 

PMID- 24439424
TI  - Impact of nutritional parameter variations during definitive chemoradiotherapy in
      locally advanced oesophageal cancer.
AB  - BACKGROUND: Undernutrition is frequently observed in patients with a locally
      advanced oesophageal carcinoma. However, variations of nutritional parameters
      during chemoradiotherapy have not been thoroughly investigated. AIM: To evaluate
      the characteristics and the impact of nutritional variations during treatment.
      METHODS: Weight loss, body mass index (BMI), serum albumin level and daily food
      intake at baseline and during treatment (T1=week 1; T2=week 5 or 8; T3=week 11)
      were retrospectively analyzed in 101 patients with oesophageal carcinoma.
      RESULTS: Significant variations occurred during chemoradiotherapy with a decrease
      in serum albumin level (p<0.001), body mass index (p<0.001) and weight (p<0.001).
      Response rate to treatment was significantly lower in patients with
      undernutrition at T1 (p=0.05), from T1 to T2 (p=0.01) and from T1 to T3 (p=0.04).
      Median overall survival was 25 months in patients with persistent undernutrition
      from T1 to T2 vs 42 months in wellnourished patients from T1 to T2 and those
      malnourished only at T1 or T2 (p=0.05). In responders, patients presenting with a
      lower weight or a lower food intake from T1 to T3 had worse survival (33 vs 59
      months, p<0.001 and 29 vs 61 months, p=0.001, respectively). CONCLUSION:
      Significant variations of nutritional parameters occurred during
      chemoradiotherapy with a worse impact on response and survival.

PMID- 24439425
TI  - The glypican 3 hepatocellular carcinoma marker regulates human hepatic stellate
      cells via Hedgehog signaling.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) frequently represents two diseases as
      it often arises in the setting of cirrhosis caused by the proliferation and
      activation of hepatic stellate cells (HSCs). Previously, we identified that
      Hedgehog (Hh) signaling regulates HSC viability and fibrinogenesis, as well as
      HCC tumorigenesis. Although it is increasingly recognized that HSCs and HCCs
      communicate via paracrine signaling, Hh's role in this process is just emerging.
      We hypothesized that a secreted HCC tumor marker and Hh mediator, glypican 3
      (GPC3), may regulate HSC. METHODS: Using three human HCC lines (Hep3B, PLC/PRF/5
      and SK-Hep-1) and one Hh-responsive human HSC line (LX-2), we developed two in
      vitro models of HCC-to-HSC paracrine signaling using a Transwell coculture system
      and HCC-conditioned media. We then evaluated the effects of these models, as well
      as GPC3, on HSC viability and gene expression. RESULTS: Using our coculture and
      conditioned media models, we demonstrate that the three HCC lines decrease HSC
      viability. Furthermore, we demonstrate that recombinant GPC3 dose-dependently
      decreases the LX-2 viability while inhibiting the expression of Hh target genes
      that regulate HSC viability. Finally, GPC3's inhibitory effects on cell viability
      and Hh target gene expression are partially abrogated by heparin, a competitor
      for GPC3 binding. CONCLUSIONS: For the first time, we show that GPC3, an HCC
      biomarker and Hh mediator, regulates human HSC viability by regulating Hh
      signaling. This expands on existing data suggesting a role for tumor-stroma
      interactions in the liver and suggests that GPC3 plays a role in this process.

PMID- 24439426
TI  - Tumor antigenicity revealed.
AB  - The extent to which mutated peptide antigens encoded by somatic mutations
      contribute to tumor antigenicity in human cancer patients has been unclear. Two
      recent studies using tumor exome sequencing to predict candidate mutated antigens
      provide insight into this question. 

PMID- 24439435
TI  - Eyewear contamination levels in the operating room: infection risk.
AB  - We investigated eyewear contamination levels in the operating room to assess
      infection risk and inform protocol development. Microbial contamination after use
      was found in 37.7% of disposable and 94.9% of reusable eyewear pieces. After
      disinfection, 74.4% of reusable eyewear also cultured positive. Disposable
      eyewear may reduce intercase contamination risk. Reusable eyewear may carry
      ongoing bioburden and, thus, contribute to operating room environment risk.
      Eyewear with antimicrobial material or components could reduce risk. Alternative
      decontamination methods for reusable eyewear should be evaluated. 

PMID- 24439436
TI  - [Paradoxical effect of obesity on functional capacity assessed by ergospirometry
      test in patients with dilated cardiomyopathy].

PMID- 24439437
TI  - Evaluation and adoption of new technology in glaucoma surgery.

PMID- 24439438
TI  - Anterior stromal puncture for the treatment of recurrent corneal erosion
      syndrome: patient clinical features and outcomes.
AB  - PURPOSE: To evaluate the clinical features and outcomes of patients with
      recurrent corneal erosion syndrome who underwent anterior stromal puncture. STUDY
      DESIGN: Retrospective, nonrandomized, consecutive case series. METHODS: Database
      search of patients from 2003-2013 who underwent anterior stromal puncture was
      conducted at a tertiary care hospital cornea clinic. Charts of 30 patients (35
      eyes) were reviewed. Outcome measures included demographics, laterality, history
      of corneal trauma, prior ocular history, frequency and duration of symptoms,
      failed treatments, signs on examination, degree of symptom resolution, additional
      treatments needed, and complications. RESULTS: Mean patient age at presentation
      was 37 (+/- 11.5 SD) years, 60% were male. A total of 83.3% of patients had
      unilateral and 16.7% had bilateral involvement. In all, 62.9% of eyes had prior
      history of corneal trauma and 2.9% had prior laser-assisted in situ
      keratomileusis. Ninety-seven percent of eyes had symptoms of pain upon awakening
      refractory to conservative treatment. In 97% of eyes, there were findings of
      microcysts, fingerprint lines, loose epithelium, and/or faint scars. Mean follow
      up was 14 months (range: 3-120 months). At final follow-up, 62.9% of eyes were
      symptom free and 37.1% experienced milder episodes. Seventeen percent required
      additional treatment: 16.6% superficial keratectomy, 66% repeat anterior stromal
      puncture, and 16.7% phototherapeutic keratectomy. No complications were observed.
      CONCLUSION: Anterior stromal puncture using a short (5/8 inch) 25 gauge bent
      needle is a simple, safe, and cost-effective procedure for symptomatic relief in
      patients with recurrent corneal erosion syndrome refractive to conservative
      measures. Repeat treatment may be performed prior to additional surgical
      intervention.

PMID- 24439439
TI  - Long-term follow-up of tacrolimus ointment for treatment of atopic
      keratoconjunctivitis.
AB  - PURPOSE: To evaluate the long-term clinical outcomes of 0.1% tacrolimus
      dermatologic ointment (Protopic) in cases of refractory atopic
      keratoconjunctivitis (AKC). DESIGN: Prospective, nonrandomized, noncontrolled
      case series. METHODS: Twenty-two eyes from 11 patients with severe AKC who were
      treated with 0.1% tacrolimus ointment were followed prospectively. The mean age
      of the patients was 32.27 +/- 12.7 years (range, 19-61 years). Each patient
      completed a follow-up period of at least 48 months, during which the signs and
      symptoms of AKC were assessed. Changes in the total scores of signs and symptoms
      from baseline were recorded at each visit, and the main outcome measure was the
      clinical response to topical tacrolimus treatment. RESULTS: Dramatic improvements
      in clinical signs and symptoms were achieved 1 week after starting topical
      tacrolimus treatment, and complete clinical resolution was observed in almost all
      patients 6 weeks after starting treatment. Treatment was gradually reduced, with
      increasing intervals between applications. Eight patients remained asymptomatic
      for up to 3 years, although recurrence occurred in 3 patients who attempted to
      discontinue treatment. All patients complained of a mild burning sensation upon
      application of the ointment. No additional medications were required to provide
      relief, and no patient discontinued treatment because of adverse drug effects. No
      drug-related ocular complications were encountered, and no significant changes in
      visual acuity or refraction were documented. CONCLUSIONS: Tacrolimus dermatologic
      ointment is a potentially safe and effective treatment for AKC cases refractory
      to standard treatment and may substitute for steroid treatments aimed at
      controlling disease activity.

PMID- 24439441
TI  - Clinical findings of acquired vitelliform lesions associated with retinal pigment
      epithelial detachments.
AB  - PURPOSE: To study clinical findings associated with acquired vitelliform lesions
      in retinal pigment epithelial detachments (PEDs). DESIGN: Retrospective,
      interventional, consecutive case series. METHODS: We retrospectively reviewed 32
      eyes of 24 patients (22 men, 2 women; age range [mean], 58-85 [73.7] years) with
      acquired vitelliform lesions. RESULTS: All eyes had acquired vitelliform lesions
      in the central macula associated with a serous PED at baseline. Of the 32 eyes,
      30 (93.8%) were observed for 12 months, 26 (81.3%) for 24 months, and 17 (53.1%)
      for 36 months. The mean logarithm of the minimal angle of resolution best
      corrected visual acuity (BCVA) levels were 0.19 at month 12, 0.28 at month 24,
      and 0.25 at month 36, none of which differed significantly from baseline. The
      mean changes in the BCVA were declines of 0.38, 1.29, and 1.21 lines at months
      12, 24, and 36, respectively. Of 7 eyes treated with 3 consecutive monthly
      intravitreal injections of ranibizumab, the serous PEDs remained in all 7 eyes
      and the mean changes of BCVA were a decline of 2.40 lines 12 months after the
      first injection and a decline of 3.58 lines at the final visit. In the 24
      untreated eyes, the mean change in the BCVA was a decline of 0.25 line at the
      final visit, which differed significantly (P = .021) compared with that of the
      treated eyes at the final visit. CONCLUSION: Intravitreal injections of
      ranibizumab were ineffective because of the absence of resolution of the PEDs and
      the declines in VA.

PMID- 24439440
TI  - In vitro susceptibility of filamentous fungal isolates from a corneal ulcer
      clinical trial.
AB  - PURPOSE: To describe the minimum inhibitory concentration (MIC) of fungal
      isolates to natamycin and voriconazole, and to compare these MICs to previous
      ocular susceptibility studies. DESIGN: Experimental laboratory study using
      isolates from a randomized clinical trial. METHODS: The Mycotic Ulcer Treatment
      Trial I was a randomized, double-masked, multicenter trial comparing topical
      natamycin and voriconazole for fungal keratitis treatment. Susceptibility testing
      to natamycin and voriconazole were performed according to Clinical and Laboratory
      Standards Institute methods. The relationship between organism and MIC was
      assessed. A literature review was performed to compare results to previous ocular
      susceptibility studies. RESULTS: Of the 323 patients enrolled in the trial, MICs
      were available for 221 (68%). Fusarium (n = 126) and Aspergillus species (n = 52)
      were the most commonly isolated organisms. MICs to natamycin and voriconazole
      were significantly different across all genera (P < .001). The MIC median (MIC50)
      and 90th percentile (MIC90) for natamycin were equal to or higher than
      voriconazole for all organisms except Curvularia species. Compared to other
      organisms, Fusarium species isolates had the highest MICs to voriconazole and
      Aspergillus flavus isolates had the highest MICs to natamycin. Our results were
      similar to previous reports except that the voriconazole MIC90 against
      Aspergillus species was 2-fold higher and the natamycin MIC90 against Aspergillus
      fumigatus was 4-fold higher in our study. CONCLUSION: In this large
      susceptibility study, Fusarium isolates were least susceptible to voriconazole
      and A flavus isolates were least susceptible to natamycin when compared to other
      filamentous fungi. In the future, susceptibility testing may help guide therapy
      if performed in a timely manner.

PMID- 24439442
TI  - Presence of foveal bulge in optical coherence tomographic images in eyes with
      macular edema associated with branch retinal vein occlusion.
AB  - PURPOSE: To determine whether a significant correlation exists between the
      presence of a bulge in the photoreceptor inner segment/outer segment (IS/OS) line
      and the best-corrected visual acuity (BCVA) in eyes with resolved macular edema
      associated with branch retinal vein occlusion (BRVO). DESIGN: Retrospective,
      observational case series. METHODS: We retrospectively reviewed the medical
      records of patients who had a complete resolution of macular edema and had an
      intact IS/OS line in the central fovea in the spectral-domain optical coherence
      tomographic (SDOCT) images. Thirty-one eyes with macular edema associated with
      BRVO (BRVO group) and 31 unaffected fellow eyes (control group) of 31 patients
      were evaluated. In normal eyes, the intact IS/OS line determined by SDOCT has a
      bulge at the central fovea, called the foveal bulge. The eyes in the BRVO group
      were classified by the presence or absence of foveal bulge, and the
      characteristics of the 2 groups were compared. RESULTS: A foveal bulge was
      present in 7 of 31 eyes in the BRVO group. The incidence of a foveal bulge was
      significantly lower in the BRVO group (22.6%) than in the control group (100%; P
      < .0001). All 7 eyes with foveal bulge had a decimal BCVA of >=1.0 at the final
      visit. The incidence of a foveal bulge was significantly higher in eyes with BCVA
      of >=1.0 (77.8%) than in the eyes with BCVA of <1.0 (0%; P < .0001). CONCLUSIONS:
      The foveal bulge is a good marker of the functional properties of the fovea in
      eyes with resolved macular edema associated with BRVO.

PMID- 24439443
TI  - In vivo imaging of cortical vitreous using 1050-nm swept-source deep range
      imaging optical coherence tomography.
AB  - PURPOSE: To image the cortical vitreous, determine the prevalence of the bursa
      premacularis and space of Martegiani, and measure the dimensions of the bursa
      using the new 1050-nm swept-source deep range imaging optical coherence
      tomography (DRI OCT-1 Atlantis). DESIGN: Retrospective cross-sectional study.
      METHODS: One hundred and nineteen consecutive patients (5-100 years) underwent an
      OCT scan using 1050-nm swept-source deep range imaging optical coherence
      tomography. Prevalence of the bursa premacularis and space of Martegiani and the
      stage of posterior vitreous detachment (PVD) were determined. The horizontal
      (width) and anteroposterior (depth) dimensions of the bursa were recorded along
      with the patient's age. RESULTS: A bursa was detected in 57.1% (136/238) of eyes.
      The bursa and space of Martegiani coexisted in 97.8% of eyes. Prevalence of
      detected bursa was 84.5% in eyes with either no PVD or perifoveal PVD only; the
      prevalence fell with further increases in the extent of PVD. Prevalence of
      detected bursa was 75.4% in patient group aged 0-60 years and 38% in the group
      aged 60-100 years. Mean width was 7001 MUm (range: 3354-10 316 MUm, SD: 1412
      MUm). Mean depth was 416 MUm (range: 31-1189 MUm, SD: 187 MUm). Width and depth
      of the bursa did not correlate with age (R(2) width = 0.0316; R(2) depth =
      0.0108). Bilateral bursa tended to be symmetrical in width but less so in depth
      (R(2) width = 0.63, P < .001; R(2) depth = 0.33, P < .001). CONCLUSION: Swept
      source OCT has allowed us to demonstrate the almost invariable coexistence of the
      bursa premacularis and space of Martegiani. Swept-source OCT can image both in
      patients from as early as the first to as late as the tenth decade of life.

PMID- 24439444
TI  - Reply: To PMID 23810473.

PMID- 24439445
TI  - Retained lens fragments after cataract surgery: outcomes of same-day vs later
      pars plana vitrectomy.

PMID- 24439446
TI  - EURECCA consensus conference highlights about colon & rectal cancer
      multidisciplinary management: the radiology experts review.
AB  - Some interesting shifts have taken place in the diagnostic approach for detection
      of colorectal lesions over the past decade. This article accompanies the recent
      EURECCA consensus group reccomendations for optimal management of colon and
      rectal cancers. In summary, imaging has a crucial role to play in the diagnosis,
      staging assessment and follow up of patients with colon and rectal cancer. Recent
      advances include the use of CT colonography instead of Barium Enema in the
      diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern
      mutlidetector CT scanning techniques have also shown improvements in prognostic
      stratification of patients with colonic cancer and clinical trials are underway
      testing the selective use of neoadjuvant therapy for imaging identified high risk
      colon cancers. In rectal cancer, high resolution MRI with a voxel size less or
      equal to 3 * 1 * 1 mm3 on T2-weighted images has a proven ability to accurately
      stage patients with rectal cancer. Moreover, preoperative identification of
      prognostic features allows stratification of patients into different prognostic
      groups based on assessment of depth of extramural spread, relationship of the
      tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI).
      These poor prognostic features predict an increased risk of local recurrence
      and/or metastatic disease and should form the basis for preoperative local
      staging and multidisciplinary preoperative discussion of patient treatment
      options. 

PMID- 24439447
TI  - Rapid detection of Enterococcus spp. direct from blood culture bottles using
      Enterococcus QuickFISH method: a multicenter investigation.
AB  - The performance of a diagnostic method for detection and identification of
      Enterococcus spp. directly from positive blood culture was evaluated in a
      clinical study. The method, Enterococcus QuickFISH BC, is a second-generation
      peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH) test, which
      uses a simplified, faster assay procedure. The test uses fluorescently labeled
      PNA probes targeting 16S rRNA to differentiate Enterococcus faecalis from other
      Enterococcus spp. by the color of the cellular fluorescence. Three hundred fifty
      six routine blood culture samples were tested; only 2 discordant results were
      recorded. The sensitivities for detection of Enterococcus faecalis and non
      faecalis Enterococcus were 100% (106/106) and 97.0% (65/67), respectively, and
      the combined specificity of the assay was 100%. The combined positive and
      negative predictive values of the assay were 100% (171/171) and 98.9% (185/187),
      respectively. 

PMID- 24439448
TI  - First autochthone case of sporotrichosis by Sporothrix globosa in Portugal.
AB  - In this study, we characterize the first autochthone case of human sporotrichosis
      reported in Lisbon, Portugal. Phenotypic and genotypic characterization revealed
      that the infection was caused by Sporothrix globosa. We conclude that
      sporotrichosis may be underdiagnosed particularly in Southern Europe and suggest
      Portugal as an emerging area for this fungal infection. 

PMID- 24439449
TI  - Comparison of the CHROMagarTM KPC, Remel SpectraTM CRE, and a direct ertapenem
      disk method for the detection of KPC-producing Enterobacteriaceae from perirectal
      swabs.
AB  - In a comparison of 3 agar plate methods, we found that a novel chromogenic
      medium, Remel SpectraTM CRE, had the best overall sensitivity (97.8%) when
      compared to the CHROMagarTM KPC (76.6%) and a direct ertapenem disk method
      (83.0%) for the detection of blaKPC-positive Enterobacteriaceae from perirectal
      swabs. 

PMID- 24439450
TI  - Homeopathic pathogenetic trials and provings: the need for harmonized guidelines.

PMID- 24439452
TI  - High-dilution effects revisited. 1. Physicochemical aspects.
AB  - Several lines of evidence suggest that homeopathic high dilutions (HDs) can
      effectively have a pharmacological action, and so cannot be considered merely
      placebos. However, until now there has been no unified explanation for these
      observations within the dominant paradigm of the dose-response effect. Here the
      possible scenarios for the physicochemical nature of HDs are reviewed. A number
      of theoretical and experimental approaches, including quantum physics,
      conductometric and spectroscopic measurements, thermoluminescence, and model
      simulations investigated the peculiar features of diluted/succussed solutions.
      The heterogeneous composition of water could be affected by interactive phenomena
      such as coherence, epitaxy and formation of colloidal nanobubbles containing
      gaseous inclusions of oxygen, nitrogen, carbon dioxide, silica and, possibly, the
      original material of the remedy. It is likely that the molecules of active
      substance act as nucleation centres, amplifying the formation of supramolecular
      structures and imparting order to the solvent. Three major models for how this
      happens are currently being investigated: the water clusters or clathrates, the
      coherent domains postulated by quantum electrodynamics, and the formation of
      nanoparticles from the original solute plus solvent components. Other theoretical
      approaches based on quantum entanglement and on fractal-type self-organization of
      water clusters are more speculative and hypothetical. The problem of the
      physicochemical nature of HDs is still far from to be clarified but current
      evidence strongly supports the notion that the structuring of water and its
      solutes at the nanoscale can play a key role. 

PMID- 24439453
TI  - High-dilution effects revisited. 2. Pharmacodynamic mechanisms.
AB  - The pharmacodynamics aspects of homeopathic remedies are appraised by laboratory
      studies on the biological effects at various levels (cellular, molecular and
      systemic). The major question is how these medicines may work in the body. The
      possible answers concern the identification of biological targets, the means of
      drug-receptor interactions, the mechanisms of signal transmission and
      amplification, and the models of inversion of effects according to the
      traditional 'simile' rule. These problems are handled by two experimental and
      theoretical lines, according to the doses or dilutions considered (low-medium
      versus high dilutions). Homeopathic formulations in low-medium dilutions,
      containing molecules in the range of ultra-low doses, exploit the extreme
      sensitivity of biological systems to exogenous and endogenous signals. Their
      effects are interpreted in the framework of hormesis theories and paradoxical
      pharmacology. The hypotheses regarding the action mechanisms of highly
      diluted/dynamized solutions (beyond Avogadro-Loschmidt limit) variously invoke
      sensitivity to bioelectromagnetic information, participation of water chains in
      signalling, and regulation of bifurcation points of systemic networks. High
      dilution pharmacology is emerging as a pioneering subject in the domain of
      nanomedicine and is providing greater plausibility to the puzzling claims of
      homeopathy. 

PMID- 24439454
TI  - Experimental evidence of stable water nanostructures in extremely dilute
      solutions, at standard pressure and temperature.
AB  - This paper presents the results of several experimental methods (FT-IR
      spectroscopy, UV-vis spectroscopy, fluorescence microscopy (FM), Atomic Force
      Microscopy (AFM)) evidencing structural changes induced in extremely diluted
      solutions (EDS), which are prepared by an iterated process of centesimal (1:100)
      dilution and succussion (shaking). The iteration is repeated until an extremely
      high dilution is reached, so that the composition of the solution becomes
      identical to that of the solvent--in this case water--used to prepare it. The
      experimental observations reveal the presence of supramolecular aggregates
      hundreds of nanometres in size in EDS at ambient pressure and temperature, and in
      the solid state. These findings confirm the hypothesis--developed thanks to
      previous physico-chemical investigations--that formation of water aggregates
      occurs in EDS. The experimental data can be analyzed and interpreted with
      reference to the thermodynamics of far-from-equilibrium systems and irreversible
      processes.

PMID- 24439455
TI  - Characteristics of patients consulting their regular primary care physician
      according to their prescribing preferences for homeopathy and complementary
      medicine.
AB  - BACKGROUND: Homeopathic care has not been well documented in terms of its impact
      on patients' utilization of drugs or other complementary and alternative
      medicines (CAM). The objective of this study was to describe and compare patients
      who visit physicians in general practice (GPs) who prescribe only conventional
      medicines (GP-CM), regularly prescribe homeopathy within a mixed practice (GP
      Mx), or are certified homeopathic GPs (GP-Ho). MATERIAL AND METHODS: The EPI3
      LASER study was a nationwide observational survey of a representative sample of
      GPs and their patients from across France. Physicians recorded their diagnoses
      and prescriptions on participating patients who completed a self-questionnaire on
      socio-demographics, lifestyle, quality of life Short Form 12 (SF-12) and the
      complementary and alternative medicine beliefs inventory (CAMBI). RESULTS: A
      total of 6379 patients (participation rate 73.1%) recruited from 804 GP practices
      participated in this survey. Patients attending a GP-Ho were slightly more often
      female with higher education than in the GP-CM group and had markedly healthier
      lifestyle. They did not differ greatly in their comorbidities or quality of life
      but exhibited large differences in their beliefs in holistic medicine and natural
      treatments, and in their attitude toward participating to their own care. Similar
      but less striking observations were made in patients of the GP-Mx group.
      CONCLUSION: Patients seeking care with a homeopathic GP did not differ greatly in
      their socio-demographic characteristics but more so by their healthier lifestyle
      and positive attitude toward CAM. Further research is needed to explore the
      directionality of those associations and to assess the potential economic
      benefits of homeopathic management in primary care.

PMID- 24439458
TI  - Beijing genotype of Mycobacterium tuberculosis is significantly associated with
      linezolid resistance in multidrug-resistant and extensively drug-resistant
      tuberculosis in China.
AB  - Linezolid (LNZ) is a promising antimicrobial agent for the treatment of multidrug
      resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). To
      investigate the efficacy of LNZ among MDR-TB and XDR-TB in China, the LNZ
      susceptibility of 158 MDR-TB isolates from the national drug resistance survey
      was determined by the minimum inhibitory concentration method. The 158 MDR-TB
      isolates were also sequenced in the 23S rRNA, rplC and rplD genes conferring LNZ
      resistance and were typed using spoligotyping to identify the Beijing genotype of
      Mycobacterium tuberculosis. Overall, the prevalence of LNZ-resistant isolates was
      10.8% (17/158) among MDR-TB isolates circulating in China. Beijing genotype was
      significantly associated with LNZ resistance in MDR-TB and XDR-TB (odds
      ratio=4.66, 95% confidence interval 1.03-21.16; P=0.033). In addition, a higher
      frequency of LNZ-resistant isolates was observed among XDR-TB strains (60%)
      compared with the MDR (5.6%; P<0.001) and pre-XDR groups (12.2%; P=0.004).
      Mutations in 23S rRNA and rplC were responsible for only 29.4% of LNZ-resistant
      M. tuberculosis among MDR-TB isolates, and a novel non-synonymous substitution
      His155Asp in rplC was first identified to be contributing to low-level LNZ
      resistance (2MUg/mL) in M. tuberculosis. The unsatisfactory correlation between
      mutant genotypes highlights the urgent need to investigate another mechanism for
      LNZ resistance that has not yet been described. 

PMID- 24439457
TI  - Systemic DNA damage responses: organismal adaptations to genome instability.
AB  - DNA damage checkpoints are important tumor-suppressor mechanisms that halt cell
      cycle progression to allow time for DNA repair, or induce senescence and
      apoptosis to remove damaged cells permanently. Non-cell-autonomous DNA damage
      responses activate the innate immune system in multiple metazoan species. These
      responses not only enable clearance of damaged cells and contribute to tissue
      remodeling and regeneration but can also result in chronic inflammation and
      tissue damage. Germline DNA damage-induced systemic stress resistance (GDISR) is
      mediated by an ancestral innate immune response and results in organismal
      adjustments to the presence of damaged cells. We discuss GDISR as an organismal
      DNA damage checkpoint mechanism through which elevated somatic endurance can
      extend reproductive lifespan when germ cells require extended time for restoring
      genome stability. 

PMID- 24439459
TI  - Locomotion in degus on terrestrial substrates varying in orientation -
      implications for biomechanical constraints and gait selection.
AB  - To gain new insights into running gaits on sloped terrestrial substrates, metric
      and selected kinematic parameters of the common degu (Octodon degus) were
      examined. Individuals were filmed at their maximum voluntary running speed using
      a high-speed camera placed laterally to the terrestrial substrate varying in
      orientations from -30 degrees  to +30 degrees , at 10 degrees  increments. Degus
      used trotting, lateral-sequence (LS) and diagonal-sequence (DS) running gaits at
      all substrate orientations. Trotting was observed across the whole speed range
      whereas DS running gaits occurred at significantly higher speeds than LS running
      gaits. Metric and kinematic changes on sloped substrates in degus paralleled
      those noted for most other mammals. However, the timing of metric and kinematic
      locomotor adjustments differed significantly between individual degus. In
      addition, most of these adjustments took place at 10 degrees  rather than 30
      degrees  inclines and declines, indicating significant biomechanical demands even
      on slightly sloped terrestrial substrates. The results of this study suggest that
      DS and LS running gaits may represent an advantage in small to medium-sized
      mammals for counteracting some level of locomotor instability. Finally, changes
      in locomotor parameters of the forelimbs rather than the hindlimbs seem to play
      an important role in gait selection in small to medium-sized mammals. 

PMID- 24439460
TI  - The impact of a hand therapy screening on patients referred for surgical opinion.

PMID- 24439461
TI  - The impact of a hand therapy screening on patients referred for surgical opinion 
      reply.

PMID- 24439463
TI  - Noninvasive mechanical ventilation. Reflections on home monitoring.

PMID- 24439462
TI  - Refractive changes after pharmacologic resolution of diabetic macular edema.
AB  - PURPOSE: To determine precisely the mean change in refractive power induced by
      treatment in patients with diabetic macular edema (DME). DESIGN: Prospective,
      randomized study. PARTICIPANTS: Fifty eyes of 50 consecutive patients with
      clinically significant macular edema receiving all 3 types of current state-of
      the-art treatment with intravitreal antiedematous substances (ranibizumab,
      bevacizumab, or triamcinolone). METHODS: Patients were followed up at monthly
      intervals and were treated following a standardized pro re nata regimen according
      to protocol. Best-corrected visual acuity (BCVA) was determined by certified
      visual acuity examiners. The refractive power of the treated eyes was determined
      using a push-plus technique. The change in refraction between baseline and the
      visit when the macula was completely dry or when the central subfield thickness
      (CST) measured by optical coherence tomography had reached the thinnest level was
      analyzed. MAIN OUTCOME MEASURES: Spherical equivalent refraction (SER) and CST.
      RESULTS: Fifty eyes of 50 patients received intravitreal therapy using
      ranibizumab (n = 11), bevacizumab (n = 20), or triamcinolone (n = 19). Mean BCVA
      was 0.33+/-0.23 logarithm of the minimum angle of resolution (logMAR) and mean
      CST was 492+/-130 MUm. The mean SER was 0.41+/-2.06 diopters (D) at baseline. The
      BCVA at the time of optimal retinal morphologic features was 0.24+/-0.2 logMAR,
      mean CST was 300+/-78 MUm, and mean change in SER was -0.01+/-0.46 D. Changes is
      BCVA and CST were statistically significant (P < 0.0001), but the SER change was
      not (P = 0.824). CONCLUSIONS: Appropriate spectacle correction can be prescribed
      to patients with DME any time during ongoing therapy using antiedematous
      substances because resolution of retinal thickening is not associated with an
      increased risk of a myopic shift.

PMID- 24439464
TI  - Traumatic hemothorax caused by solitary costal exostosis.

PMID- 24439466
TI  - Do right what is right.

PMID- 24439465
TI  - Endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions. A
      controlled study with fluoroscopy.
AB  - INTRODUCTION: Fluoroscopy-guided bronchoscopy is usually performed for the
      diagnosis of peripheral pulmonary lesions (PPL), but the diagnostic yield varies
      widely among studies. Endobronchial ultrasound (EBUS) can increase the diagnostic
      yield of bronchoscopic diagnosis of PPL. OBJECTIVE: To compare the diagnostic
      yield of fluoroscopy-guided bronchoscopy and EBUS with fluoroscopy-guided
      bronchoscopy in the study of PPL. METHODS: All patients who underwent
      bronchoscopy to study PPL from January 2009 to December 2012 were prospectively
      included. 145 consecutive patients were randomly distributed in two groups: EBUS
      and fluoroscopy (50 patients, 71.3 +/- 8.2 years) or fluoroscopy alone (95
      patients, 68 +/- 10.5 years). The mean diameter of the lesions was 41.97 +/-
      19.22 mm. Cytological brushing and transbronchial biopsies were obtained. All
      procedures were performed under fluoroscopic guidance with intravenous conscious
      sedation. EBUS was performed using an endoscopic ultrasound system equipped with
      a 20-MHz radial miniprobe introduced via a guide-sheath. Bronchoscopist,
      cytologist, study protocol, techniques and tools were the same throughout the
      whole study. RESULTS: 129 (89%) patients had malignant disease. A diagnosis with
      bronchoscopy was established in 105 (72.4%) patients. EBUS plus fluoroscopy
      obtained a diagnostic yield in 78% of patients and fluoroscopy alone in 69.5%
      (non-significant). In contrast, for lesions smaller than 30 mm, EBUS plus
      fluoroscopy guidance provided significantly greater diagnostic performance than
      fluoroscopy alone (90 vs. 52%; P=.05). CONCLUSIONS: Bronchoscopy under EBUS plus
      fluoroscopy guidance is a technique that has become useful for the diagnostic of
      LPPs, especially those smaller than 30 mm in diameter.

PMID- 24439467
TI  - CCTTT pentanucleotide repeats in inducible nitric oxide synthase gene expression
      in patients with pulmonary arterial hypertension.
AB  - INTRODUCTION: One of the pathways involved in pulmonary arterial hypertension
      (PAH) is the nitric oxide (NO) pathway. A polymorphism in the inducible NO
      synthase (NOS2) gene has been described, consisting of the CCTTT pentanucleotide
      repeat, which causes a reduction in NO production. The aim of this study was to
      determine if this polymorphism increases susceptibility to developing PAH.
      METHODS: Sixty four patients with a diagnosis of PAH groupsi and iv and 50
      healthy controls were compared. DNA genotyping of the samples for this
      polymorphism was performed using PCR. The distribution between both groups was
      compared and correlated with clinical and haemodynamic parameters and therapeutic
      response. RESULTS: A significantly different distribution was observed in the
      number of repeats between patients and controls (P<.0001). When the samples were
      categorised by short forms (both alleles with less than 12repeats) and long forms
      (>=12 repeats), it was observed that the former had an almost 4-fold risk of
      developing PAH (odds ratio: 3.83; 95%CI: 1.19-12.32, P=.024). There were no
      differences between the most common types of PAH, either in therapeutic response
      or survival. There was no correlation between haemodynamic parameters and the
      number of repeats in the patients, and only a weak correlation with systolic PAH.
      CONCLUSIONS: There are significant differences in the distribution of the NOS2
      promotor CCTTT polymorphism between patients with PAH and the healthy population.
      A minor CCTTT pentanucleotide repeat in the NOS2 gene may increase the risk of
      developing PAH.

PMID- 24439468
TI  - Pleural effusion Due to Streptococcus milleri: Case descriptions.
AB  - In this study we analyzed the characteristics of patients with pleural effusion
      secondary to Streptococcus milleri studied retrospectively between January and
      March 2013 and found seven patients with a mean age of 60 years, 43% of which
      were smokers and 57% with a drinking habit. The most common associated factors
      were alcoholism, previous pneumonia and diabetes. Other bacteria were identified
      as Enterobacter aerogenes, Bacteroides and Prevotella intermedia capillosus in
      two patients. The mean duration of antibiotic therapy was 28 days; six patients
      underwent pleural drainage by chest tube and one patient needed surgery due to
      poor clinical progress. The mean duration of hospitalization was 30 days with
      satisfactory outcome in all cases, despite some changes in residual function.

PMID- 24439469
TI  - Intracellular bacteria in placental basal plate localize to extravillous
      trophoblasts.
AB  - We previously showed that intracellular bacteria are present in the human
      placental maternal-fetal interface (basal plate). To determine the bacterial
      niche, basal plate biopsies were 1) examined histologically, and 2) cultured ex
      vivo, infected with either gram negative (Escherichia coli) or positive (Listeria
      monocytogenes) bacteria, and examined by histological staining,
      immunofluorescence, and transmission electron microscopy. We found bacteria in
      fetal extravillous trophoblasts (EVTs) in basal plate biopsies. Both E. coli and
      L. monocytogenes also predominantly invaded EVTs in basal plate explants where
      they replicated and formed clusters or existed as single organisms. EVTs are the
      cell type most susceptible to bacterial colonization, likely due to their
      expression of major histocompatibility antigen and immune-privileged status.
      Pathogens persisting and replicating in the EVTs may constitute a source of
      intrauterine colonization that leads to adverse outcomes such as preterm birth.

PMID- 24439470
TI  - Fluoxetine combined with clorazepate dipotassium and behaviour modification for
      treatment of anxiety-related disorders in dogs.
AB  - The effectiveness of clorazepate dipotassium combined with fluoxetine and a
      behaviour modification programme for the treatment of anxiety disorders in dogs
      was investigated. Forty dogs with anxiety disorders were initially enrolled and
      36 dogs completed the trial. Dogs were classified into two behavioural categories
      (anxious dogs with aggression and anxious dogs without aggression) according to
      their presenting complaints, and were also subdivided into males, females,
      juveniles and adults. The dog owners were provided with a behaviour modification
      plan for their dogs to be commenced in the first week of therapy. Clorazepate
      dipotassium was administered PO at 1.0 mg/kg every 24 h for 4 weeks, and
      fluoxetine was administered PO at 1.0 mg/kg every 24 h for 10 weeks. Therapy with
      both drugs was initiated simultaneously. Improvement was reported in 25/36 dogs.
      Significant differences in treatment effects were observed between anxious dogs
      with aggression and anxious dogs without aggression (P<0.05). Positive
      correlations between owner compliance with the treatment plan and reported
      improvement achieved during three periods of study were also noted.

PMID- 24439471
TI  - Nutritional management of inherited copper-associated hepatitis in the Labrador
      retriever.
AB  - Canine hereditary copper-associated hepatitis is characterized by gradual hepatic
      copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at
      creating a negative copper balance with metal chelators, of which D-penicillamine
      is the most commonly used. D-penicillamine often causes gastro-intestinal side
      effects and life-long continuous therapy may lead to a deficiency of copper and
      zinc. The aim of the current study was to investigate the effect of a low-copper,
      high-zinc diet as an alternative to continuous D-penicillamine treatment for the
      long-term management of canine copper-associated hepatitis. Sixteen affected
      Labrador retrievers were followed for a median time period of 19.1 months (range,
      5.9-39 months) after being effectively treated with D-penicillamine. The dogs
      were maintained on a diet containing 1.3+/-0.3 mg copper/1000 kcal and 64.3+/-5.9
      mg zinc/1000 kcal. Liver biopsies were taken every 6 months for histological
      evaluation and copper determination. Plasma alanine aminotransferase (ALT) and
      alkaline phosphatase, as well as serum albumin were determined. Dietary treatment
      alone was sufficient to maintain hepatic copper concentration below 800 mg/kg dry
      weight liver in 12 dogs during the study period. Four dogs needed re-treatment
      with D-penicillamine. ALT activity and albumin concentration were not associated
      with hepatic copper concentration, but showed a significant association with the
      stage and grade of hepatitis respectively. In conclusion, a low-copper, high-zinc
      diet can be a valuable alternative to continuous d-penicillamine administration
      for long-term management of dogs with copper-associated hepatitis. The copper re
      accumulation rate of an individual dog should be considered in the design of a
      long-term management protocol and in determining re-biopsy intervals.

PMID- 24439472
TI  - Dural arteriovenous fistula presenting with exophthalmos and seizures.
AB  - Concomitant seizures and exophthalmos in the context of a temporal dural
      arteriovenous fistula (dAVF) has not been described before. Here, we report a 55
      year-old-male who presented with an 8-month history of progressive painless
      exophthalmos of his left eye, conjunctival chemosis, reduced vision and new onset
      complex partial seizures. Cerebral angiography demonstrated Cognard Type IIa left
      cerebral dAVF fed by branches from the left occipital artery and an accessory
      meningeal artery, with drainage to the superior ophthalmic vein. Following
      surgical obliteration of dAVF feeding vessels, our patient had dramatic
      improvement in visual acuity, proptosis and chemosis along with cessation of
      clinical seizures.

PMID- 24439473
TI  - Analysis of the quality of care in surgical treatment of colorectal cancer:
      national study. Follow-up results.
AB  - OBJECTIVES: Using the cases included in the Study on the quality of care in
      colorectal cancer conducted by the Spanish Association of Surgeons in 2008, we
      present follow-up data. METHOD: Multicenter, descriptive, longitudinal and
      prospective study of patients operated on a scheduled basis of colorectal cancer.
      35 hospitals have contributed data on 334 patients. Follow-up data: survival,
      recurrence and complications. RESULTS: Mean follow-up was 28.61+/-11.32 months.
      Follow-up by surgeon: 69.2%, tumor recurrence 23.6%, in 83.3% it was systemic;
      28.2% underwent salvage surgery. Overall survival was 76.6%, disease-free
      survival 65.6% (26.49+/-11.90 months). Tumor related mortality was 12,6%.
      Percentage of ventral hernias was 5.8%, intestinal obstruction 3.5%. CONCLUSIONS:
      Quality and results of follow-up of patients operated on for CRC in Spain are
      similar to those reported in the Scientific literature. Areas for improvement:
      follow-up, earlier diagnosis, increase adjuvant and neoadjuvant treatments and
      total mesorectal excision as standard surgery for rectal cancer.

PMID- 24439474
TI  - [Radical surgery for incidental gallbladder cancer: the value of a deferred
      pathological finding of residual disease].
AB  - BACKGROUND: Surgical treatment of gallbladder cancer is still controversial. The
      extent of the radical surgery and its therapeutic efficacy continue to be
      debated. OBJECTIVE: Analyze the efficacy of radical resection in patients with
      incidental gallbladder cancer evaluating the presence of residual disease in the
      resection specimen and analyzing the associated factors of survival. METHODS: A
      retrospective analysis of patients with incidental GC between June 1999 and June
      2010 was performed. Incidental (I) tumors were included. Data covering
      demographic features, clinical characteristics, local pathological stage,
      histological features and factors for long term survival were analyzed. p< 0.05
      were considered significant. RESULTS: A total of 28 patients: 78,6% females.
      Median age 56 years. All treated by resection of segments 4b/5 and
      lymphadenectomy. Histological examination revealed residual disease in 42% (37%
      liver), residual disease was related to tumoral (T) stage (p 0,001). Patients
      with residual disease presented a DSS and DFS of 10 and 6.5 months respectively
      vs 56 months in those without residual disease (p 0,001). Variables associated
      with survival were T stage (P .006), TNM stage (P<.001), and residual disease in
      the resected specimen (P<.001). CONCLUSIONS: Aggressive re-resection of
      incidental GC offers the only chance for cure but its efficacy depends on the
      extent of the disease found at the time of repeated surgery and in the deferred
      pathological study.

PMID- 24439475
TI  - The evolution of human rights in World Health Organization policy and the future
      of human rights through global health governance.
AB  - The World Health Organization (WHO) was intended to serve at the forefront of
      efforts to realize human rights to advance global health, and yet this promise of
      a rights-based approach to health has long been threatened by political
      constraints in international relations, organizational resistance to legal
      discourses, and medical ambivalence toward human rights. Through legal research
      on international treaty obligations, historical research in the WHO
      organizational archives, and interview research with global health stakeholders,
      this research examines WHO's contributions to (and, in many cases, negligence of)
      the rights-based approach to health. Based upon such research, this article
      analyzes the evolving role of WHO in the development and implementation of human
      rights for global health, reviews the current state of human rights leadership in
      the WHO Secretariat, and looks to future institutions to reclaim the mantle of
      human rights as a normative framework for global health governance. 

PMID- 24439476
TI  - Current progress in antiviral strategies.
AB  - The prevalence of chronic viral infectious diseases, such as human
      immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the
      emergence and re-emergence of new viral infections, such as picornaviruses and
      coronaviruses; and, particularly, resistance to currently used antiviral drugs
      have led to increased demand for new antiviral strategies and reagents. Increased
      understanding of the molecular mechanisms of viral infection has provided great
      potential for the discovery of new antiviral agents that target viral proteins or
      host factors. Virus-targeting antivirals can function directly or indirectly to
      inhibit the biological functions of viral proteins, mostly enzymatic activities,
      or to block viral replication machinery. Host-targeting antivirals target the
      host proteins that are involved in the viral life cycle, regulating the function
      of the immune system or other cellular processes in host cells. Here we review
      key targets and considerations for the development of both antiviral strategies. 

PMID- 24439477
TI  - Pricing pharmaceutical compounds under development.

PMID- 24439478
TI  - H63D mutation in hemochromatosis alters cholesterol metabolism and induces memory
      impairment.
AB  - The H63D variant of the hemochromatosis (HFE) gene, when expressed in carriers of
      the apolipoprotein E4 allele, is implicated as a risk factor for earlier onset of
      Alzheimer's disease (AD). We tested the hypothesis that like expression of
      apolipoprotein E4, expression of H63D-HFE disrupts cholesterol metabolism
      contributing to an increase in neurodegeneration and memory deficits. Analysis of
      SH-SY5Y human neuroblastoma cells transfected to stably express either wild type-
      (WT) or H63D-HFE indicated about a 50% reduction in cholesterol content in cells
      expressing H63D-HFE. This was accompanied by a significant decrease in expression
      of 3-hydroxy-3-methyl-glutaryl-CoA reductase, and a significant increase in
      expression of cholesterol 24-hydroxylase. Consistent with these studies, H67D-HFE
      (orthologous to human H63D-HFE) knock-in mice, showed a greater age dependent
      decline in brain cholesterol than WT-HFE animals and changes in expression of
      proteins regulating cholesterol metabolism. Brains of aged H67D-HFE mice also
      exhibited a significant decrease in expression of synapse proteins and a
      significant increase in caspase-3 expression relative to WT-HFE controls. H67D
      HFE mice also had a greater reduction in brain volume and poorer recognition and
      spatial memory than WT-HFE mice, symptoms associated with AD. These results
      indicate that the alterations in cholesterol metabolism associated with
      expression of H63D-HFE may contribute to the development of AD. 

PMID- 24439480
TI  - Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral
      sclerosis shifts energy generation from oxidative phosphorylation to glycolysis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      involving the progressive degeneration of motor neurons in the brain and spinal
      cord. Mitochondrial dysfunction plays a key role in ALS disease progression and
      has been observed in several ALS cellular and animal models. Here, we show that
      fibroblasts isolated from ALS cases with a Cu/Zn superoxide dismutase (SOD1)
      I113T mutation recapitulate these mitochondrial defects. Using a novel technique,
      which measures mitochondrial respiration and glycolytic flux simultaneously in
      living cells, we have shown that SOD1 mutation causes a reduction in
      mitochondrial respiration and an increase in glycolytic flux. This causes a
      reduction in adenosine triphosphate produced by oxidative phosphorylation and an
      increase in adenosine triphosphate produced by glycolysis. Switching the energy
      source from glucose to galactose caused uncoupling of mitochondria with increased
      proton leak in SOD1(I113T) fibroblasts. Assessment of the contribution of fatty
      acid oxidation to total respiration, suggested that fatty acid oxidation is
      reduced in SOD1 ALS fibroblasts, an effect which can be mimicked by starving the
      control cells of glucose. These results highlight the importance of understanding
      the interplay between the major metabolic pathways, which has the potential to
      lead to strategies to correct the metabolic dysregulation observed in ALS cases. 

PMID- 24439479
TI  - Interaction between sleep-disordered breathing and apolipoprotein E genotype on
      cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal
      elderly individuals.
AB  - Previous studies have suggested a link between sleep disordered breathing (SDB)
      and dementia risk. In the present study, we analyzed the relationship between SDB
      severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE
      alleles. A total of 95 cognitively normal elderly participants were analyzed for
      SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and
      amyloid beta 42 (Abeta-42), as well as ApoE allele status. In ApoE3+ subjects,
      significant differences were found between sleep groups for p-tau (F[df2] = 4.3,
      p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+
      subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively
      correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and
      Abeta-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea
      with 4% O2-desaturation index was correlated with lower levels of CSF Abeta-42 (r
      = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend
      toward lower CSF Abeta-42 levels. Our observations suggest that there is an
      association between SDB and CSF Alzheimer's disease-biomarkers in cognitively
      normal elderly individuals. Existing therapies for SDB such as continuous
      positive airway pressure could delay the onset to mild cognitive impairment or
      dementia in normal elderly individuals.

PMID- 24439481
TI  - De novo nonsense mutation of the FUS gene in an apparently familial amyotrophic
      lateral sclerosis case.
AB  - Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two
      third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS)
      cases. We present the first case of an ALS patient carrying a de novo nonsense
      mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently
      familial ALS. This mutation causes a phenotype characterized by a young age at
      onset, a rapid course (<24 months), and a bulbar onset with early respiratory
      involvement with a predominant lower motor neuron disease. De novo mutations
      could account for a sizable number of apparently sporadic ALS patients carrying
      mutations of ALS-related genes. 

PMID- 24439482
TI  - Novel vaccine peptide GV1001 effectively blocks beta-amyloid toxicity by
      mimicking the extra-telomeric functions of human telomerase reverse
      transcriptase.
AB  - GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase
      reverse transcriptase sequence. We investigated the effects of GV1001 against
      beta-amyloid (Abeta) oligomer-induced neurotoxicity in rat neural stem cells
      (NSCs). Primary culture NSCs were treated with several concentrations of GV1001
      and/or Abeta25-35 oligomer for 48 hours. GV1001 protected NSCs against the
      Abeta25-35 oligomer in a concentration-dependent manner. Abeta25-35 concentration
      dependently decreased viability, proliferation, and mobilization of NSCs and
      GV1001 treatment restored the cells to wild-type levels. Abeta25-35 increased
      free radical levels in rat NSCs while combined treatment with GV1001
      significantly reduced these levels. In addition, GV1001 treatment of Abeta25-35
      injured NSCs increased the expression level of survival-related proteins,
      including mitochondria-associated survival proteins, and decreased the levels of
      death and inflammation-related proteins, including mitochondria-associated death
      proteins. Together, these results suggest that GV1001 possesses neuroprotective
      effects against Abeta25-35 oligomer in NSCs and that these effects are mediated
      through mimicking the extra-telomeric functions of human telomerase reverse
      transcriptase, including the induction of cellular proliferation, anti-apoptotic
      effects, mitochondrial stabilization, and anti-aging and anti-oxidant effects.

PMID- 24439483
TI  - Dysregulated physiological stress systems and accelerated cellular aging.
AB  - Exposure to chronic stressors is associated with accelerated biological aging as
      indicated by reduced leukocyte telomere length (LTL). This impact could be
      because of chronic overactivation of the body's physiological stress systems.
      This study examined the associations between LTL and the immune system,
      hypothalamic-pituitary-adrenal axis and autonomic nervous system. LTL was
      assessed in 2936 adults from the Netherlands Study of Depression and Anxiety.
      Inflammation markers (interleukin-6, c-reactive protein, tumor necrosis factor
      alpha), hypothalamic-pituitary-adrenal-axis indicators (salivary cortisol
      awakening curve [area under the curve indicators, with respect to the ground and
      increase], evening levels, 0.5 mg dexamethasone cortisol suppression ratio), and
      autonomic nervous system measures (heart rate, respiratory sinus arrhythmia, pre
      ejection period) were determined. Linear regression analyses were performed and
      adjusted for sociodemographic, lifestyle and clinical factors. Shorter LTL was
      significantly associated with higher c-reactive protein, interleukin-6, area
      under the curve with respect to increase, and heart rate. A cumulative index
      score was calculated based on the number of highest tertiles of these 4 stress
      markers. LTL demonstrated a significant gradient within subjects ranging from
      having zero (5528 base pairs) to having 4 elevated stress markers (5371 base
      pairs, p for trend = 0.002), corresponding to a difference of 10 years of
      accelerated biological aging. Contrary to the expectations, shorter LTL was also
      associated with longer pre-ejection period, indicating lower sympathetic tone.
      This large-scale study showed that inflammation, high awakening cortisol
      response, and increased heart rate are associated with shorter LTL, especially
      when they are dysregulated cumulatively. 

PMID- 24439486
TI  - [Mesenteric polycystic lymphangioma. A rare cause of acute surgical abdomen].

PMID- 24439485
TI  - Cardiovascular risks and brain function: a functional magnetic resonance imaging
      study of executive function in older adults.
AB  - Cardiovascular (CV) risk factors, such as hypertension, diabetes, and
      hyperlipidemia are associated with cognitive impairment and risk of dementia in
      older adults. However, the mechanisms linking them are not clear. This study aims
      to investigate the association between aggregate CV risk, assessed by the
      Framingham general cardiovascular risk profile, and functional brain activation
      in a group of community-dwelling older adults. Sixty participants (mean age: 64.6
      years) from the Brain Health Study, a nested study of the Baltimore Experience
      Corps Trial, underwent functional magnetic resonance imaging using the Flanker
      task. We found that participants with higher CV risk had greater task-related
      activation in the left inferior parietal region, and this increased activation
      was associated with poorer task performance. Our results provide insights into
      the neural systems underlying the relationship between CV risk and executive
      function. Increased activation of the inferior parietal region may offer a
      pathway through which CV risk increases risk for cognitive impairment.

PMID- 24439487
TI  - Influence of apolipoprotein E gene polymorphism on development of type 2 diabetes
      mellitus in Chinese Han population: a meta-analysis of 29 studies.
AB  - OBJECTIVES: Published data regarding the association between apolipoprotein E
      (ApoE) gene polymorphism and type 2 diabetes mellitus (T2DM) risk in Chinese Han
      population were inconclusive. To derive a more precise estimation of the
      relationship between this variant and T2DM risk in Chinese Han population, we
      performed this meta-analysis. DESIGN AND METHODS: A computerized literature
      search was conducted to identify the relevant studies from PubMed, EMbase, Web of
      Science, CBMdisc, CNKI, and Google Scholar. Additionally, hand searching of the
      references of identified articles was performed. All the statistical tests were
      performed using Stata 11.0. RESULTS: A total of 29 articles with 4615 T2DM cases
      and 2867 controls were included in the present meta-analysis. The results showed
      evidence for significant association between ApoE gene polymorphism and T2DM risk
      (for epsilon2/epsilon3 vs. epsilon3/epsilon3: OR=1.37, 95% CI=1.12-1.68, P<0.01;
      for epsilon3/epsilon4 vs. epsilon3/epsilon3: OR=1.53, 95% CI=1.23-1.91, P<0.01;
      for epsilon4/epsilon4 vs. epsilon3/epsilon3: OR=1.86, 95% CI=1.22-2.84, P<0.01;
      for epsilon2 allele vs. epsilon3 allele: OR=1.28, 95% CI=1.08-1.52, P=0.01; for
      epsilon4 allele vs. epsilon3 allele: OR=1.43, 95% CI=1.22-1.68, P<0.01). In
      addition, significant association was also found between ApoE gene polymorphism
      and diabetic nephropathy (DN) risk. CONCLUSIONS: The results of this meta
      analysis suggest that the ApoE epsilon2 and epsilon4 alleles may be associated
      with increased risks of T2DM and DN in Chinese Han population. Additional well
      designed genome-wide association studies are required to confirm these results.

PMID- 24439484
TI  - Missense variant in TREML2 protects against Alzheimer's disease.
AB  - TREM and TREM-like receptors are a structurally similar protein family encoded by
      genes clustered on chromosome 6p21.11. Recent studies have identified a rare
      coding variant (p.R47H) in TREM2 that confers a high risk for Alzheimer's disease
      (AD). In addition, common single nucleotide polymorphisms in this genomic region
      are associated with cerebrospinal fluid biomarkers for AD and a common intergenic
      variant found near the TREML2 gene has been identified to be protective for AD.
      However, little is known about the functional variant underlying the latter
      association or its relationship with the p.R47H. Here, we report comprehensive
      analyses using whole-exome sequencing data, cerebrospinal fluid biomarker
      analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based
      functional studies to support the role of the TREML2 coding missense variant
      p.S144G (rs3747742) as a potential driver of the meta-analysis AD-associated
      genome-wide association studies signal. Additionally, we demonstrate that the
      protective role of TREML2 in AD is independent of the role of TREM2 gene as a
      risk factor for AD. 

PMID- 24439489
TI  - Response to Galan-Puchades and Fuentes: Taenia asiatica: neglected--but not
      forgotten--and almost certainly being quietly globalised.

PMID- 24439490
TI  - Predictors of wound infection in elective colorectal surgery. Multicenter
      observational case-control study.
AB  - INTRODUCTION: The aim of this study is to evaluate the usefulness of Vicryl
      Plus((r)) suture in reducing the rate of postoperative wound infection in
      elective colorectal surgery. METHODS: A prospective case-control multicenter
      study with 480 patients undergoing elective colorectal surgery was performed
      between 2006 and 2007. Patients were divided in 2 groups of equal sample size:
      group 1, closure of the abdominal wall using Vicryl Plus((r)) and group 2 where
      PDS II((r)) was used. The study involved 5 hospitals in the Spanish State. Wound
      infection was classified into superficial and deep. All patients diagnosed of
      wound infection during the hospital stay and up to 30 days after discharge were
      studied. For the statistical analysis Chi-square test and Fisher exact were used
      for bivariate analysis and logistic regression model for multivariate analysis.
      RESULTS: Wound infection rates were significantly lower in group 1: 14.6 vs.
      29.2. Multivariate analysis showed that risk of wound infection was higher in
      patients with cancer, lung disease, anemia, operative time greater than 2 h, lack
      of second dose intra-operative prophylactic antibiotic and laparotomy closure
      with PDS suture II((r)). CONCLUSIONS: The use of suture coated with triclosan can
      be an effective prophylactic tool in reducing wound infection rate in patients
      undergoing elective colorectal surgery.

PMID- 24439491
TI  - The foliar microbiome.
AB  - Proficient performance in plants is strongly associated with distinct microbial
      communities that live in and on their organs. We comment here on the current
      knowledge of the composition of the foliar microbiome, highlight its importance
      for plants, ecosystemic functioning, and crop yields, and propose tools and
      experiments to overcome the current knowledge gap. 

PMID- 24439492
TI  - Remote cerebellar hemorrhage as an early and potentially lethal complication of a
      discal lumbar herniation surgery.
AB  - Remote cerebellar hemorrhage (RCH) is an infrequent but serious complication
      after lumbar herniation surgery. Little is known about this complication but
      excessive cerebrospinal fluid (CSF) leakage is thought to be a leading cause of
      RCH. We describe the case of a patient suffering from a life-threatening RCH,
      which occurred a few hours after lumbar disc herniation surgery. 

PMID- 24439493
TI  - [Esophageal cancer surgery: evolution of pain management, hemodynamics and
      ventilation practices during 16 years].
AB  - OBJECTIVE: To describe the evolution of perioperative anesthesia practices in for
      esophageal cancer surgery. PATIENTS AND METHODS: We conducted an observational
      retrospective study in a single center evaluating main perioperative practices
      during 16 years (1994-2009). Statistical analysis was done on 4 chronologic
      quartiles of same sample size. RESULTS: Two hundred and seven consecutive
      patients were included during the 4 periods 1994-1997 (n=52), 1997-1999 (n=52),
      1999-2003 (n=52) and 2004-2009 (n=51). The main significant evolutions between
      the first and the fourth period were observed: (i) in ventilation: lower tidal
      volume (9.6[8.6-10.6] vs 7.6[7.0-8.3] mL/kg of ideal body weight (IBW), p<0.01),
      increased use of Positive End Expiratory Pressure (0 vs 83%, p<0.001) and
      increased use of post-operative non-invasive ventilation (0 vs 51%, p<0.001);
      (ii) in hemodynamic management: lower fluid replacement (20.6 [16.0-24.6] vs 12.6
      [9.7-16.2] mL/h/kg of IBW, p<0.001); (iii) in analgesia: increased use of
      epidural thoracic anesthesia (31 vs 57%, p<0.001). Peroperative bleeding, type of
      fluid replacement, length of mechanical ventilation, length of stay in intensive
      care unit, ventilatory free days and mortality at day 28 didn't change.
      CONCLUSIONS: During these previous years, anesthesia practices in ventilation,
      hemodynamics and analgesia for esophageal cancer surgery have changed.

PMID- 24439494
TI  - [RPR's good old days].

PMID- 24439495
TI  - ["Men in white": is white coat a medical symbol or a microbial tank?].

PMID- 24439496
TI  - [Prone positioning and pulmonary recruitment in non-optimal donors to select lung
      grafts].

PMID- 24439497
TI  - [Teletherapeutic drug administration by long distance via Internet control: back
      to the future?].

PMID- 24439498
TI  - Estimation of the limit of detection using information theory measures.
AB  - Definitions of the limit of detection (LOD) based on the probability of false
      positive and/or false negative errors have been proposed over the past years.
      Although such definitions are straightforward and valid for any kind of
      analytical system, proposed methodologies to estimate the LOD are usually
      simplified to signals with Gaussian noise. Additionally, there is a general
      misconception that two systems with the same LOD provide the same amount of
      information on the source regardless of the prior probability of presenting a
      blank/analyte sample. Based upon an analogy between an analytical system and a
      binary communication channel, in this paper we show that the amount of
      information that can be extracted from an analytical system depends on the
      probability of presenting the two different possible states. We propose a new
      definition of LOD utilizing information theory tools that deals with noise of any
      kind and allows the introduction of prior knowledge easily. Unlike most
      traditional LOD estimation approaches, the proposed definition is based on the
      amount of information that the chemical instrumentation system provides on the
      chemical information source. Our findings indicate that the benchmark of
      analytical systems based on the ability to provide information about the
      presence/absence of the analyte (our proposed approach) is a more general and
      proper framework, while converging to the usual values when dealing with Gaussian
      noise. 

PMID- 24439499
TI  - Target-induced formation of gold amalgamation on DNA-based sensing platform for
      electrochemical monitoring of mercury ion coupling with cycling signal
      amplification strategy.
AB  - Heavy metal ion pollution poses severe risks in human health and environmental
      pollutant, because of the likelihood of bioaccumulation and toxicity. Driven by
      the requirement to monitor trace-level mercury ion (Hg(2+)), herein we construct
      a new DNA-based sensor for sensitive electrochemical monitoring of Hg(2+) by
      coupling target-induced formation of gold amalgamation on DNA-based sensing
      platform with gold amalgamation-catalyzed cycling signal amplification strategy.
      The sensor was simply prepared by covalent conjugation of aminated poly-T(25)
      oligonucleotide onto the glassy carbon electrode by typical carbodiimide
      coupling. Upon introduction of target analyte, Hg(2+) ion was intercalated into
      the DNA polyion complex membrane based on T-Hg(2+)-T coordination chemistry. The
      chelated Hg(2+) ion could induce the formation of gold amalgamation, which could
      catalyze the p-nitrophenol with the aid of NaBH4 and Ru(NH3)6(3+) for cycling
      signal amplification. Experimental results indicated that the electronic signal
      of our system increased with the increasing Hg(2+) level in the sample, and has a
      detection limit of 0.02nM with a dynamic range of up to 1000nM Hg(2+). The
      strategy afforded exquisite selectivity for Hg(2+) against other environmentally
      related metal ions. In addition, the methodology was evaluated for the analysis
      of Hg(2+) in spiked tap-water samples, and the recovery was 87.9-113.8%. 

PMID- 24439500
TI  - Development of a simple and rapid solid phase microextraction-gas chromatography
      triple quadrupole mass spectrometry method for the analysis of dopamine,
      serotonin and norepinephrine in human urine.
AB  - The work aims at developing a simple and rapid method for the quantification of
      dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in human urine. The
      urinary levels of these biogenic amines can be correlated with several
      pathological conditions concerning heart disease, stress, neurological disorders
      and cancerous tumors. The proposed analytical approach is based on the use of
      solid phase microextraction (SPME) combined with gas chromatography-triple
      quadrupole mass spectrometry (GC-QqQ-MS) after a fast derivatization of both
      aliphatic amino and phenolic moieties by propyl chloroformate. The variables
      influencing the derivatization reaction were reliably optimized by the
      multivariate approach of "Experimental design". The optimal conditions were
      obtained by performing derivatization with 100MUL of propyl chloroformate and
      100MUL of pyridine. The extraction ability of five commercially available SPME
      fibers was evaluated in univariate mode and the best results were obtained using
      the polyacrylate fiber. The variables affecting the efficiency of SPME analysis
      were again optimized by the multivariate approach of "Experimental design" and,
      in particular, a central composite design (CCD) was applied. The optimal values
      were extraction in 45min at room temperature, desorption temperature at 300
      degrees C, no addition of NaCl. Assay of derivatized analytes was performed by
      using a gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS) system
      in selected reaction monitoring (SRM) acquisition. An evaluation of all
      analytical parameters demonstrates that the developed method provides
      satisfactory results. Indeed, very good linearities were achieved in the tested
      calibration range with correlation coefficient values of 0.9995, 0.9999 and
      0.9997 for DA, 5-HT and NE, respectively. Accuracies and RSDs calculated for
      between-run and tested at concentrations of 30, 200, and 800MUg L(-1) were in the
      range from 92.8% to 103.0%, and from 0.67 to 4.5%, respectively. Finally, the LOD
      values obtained can be considered very good (0.587, 0.381 and 1.23MUg L(-1) for
      DA, 5-HT and NE, respectively).

PMID- 24439501
TI  - A self-assembly pipette tip graphene solid-phase extraction coupled with liquid
      chromatography for the determination of three sulfonamides in environmental
      water.
AB  - A sensitive, economical, and miniaturized self-assembly pipette tip graphene
      solid-phase extraction (PT-G-SPE) coupled with liquid chromatography fluorescence
      detection (LC-FD) was developed for rapid extraction and determination of three
      sulfonamide antibiotics (SAs) in environmental water samples. The PT-G-SPE
      cartridge, assembled by packing 1.0mg of graphene as sorbent into a 100MUL
      pipette tip, showed high adsorption capacity for the SAs owing to the large
      surface area and unique structure of graphene. The factors that affected the
      extraction efficiency of PT-G-SPE, including sample volume, pH, sorbent amount,
      washing solvent and eluent solvent were optimized. Good linearity for SAs was
      obtained in a range of 2-4000pgmL(-1) with correlation coefficients
      (r(2))>=0.9993. The recoveries of the SAs at three spiked levels ranged from
      90.4% to 108.2% with relative standard deviations (RSD)<=6.3%. In comparison with
      other sorbents such as C18, HLB, SCX, PCX, and multiwalled carbon nanotubes, one
      advantage of using graphene as sorbent of pipette tip solid-phase extraction (PT
      SPE) was that PT-G-SPE could adsorb larger sample volume (10mL) at a small amount
      of sorbent (1mg) and low solvent consumption with good extraction efficiency,
      which not only increased the fraction of analytes to LC and the sensitivity of
      SAs determination, but also reduced the cost and pollution. 

PMID- 24439502
TI  - Improvement in the sensitivity of microfluidic ELISA through field amplified
      stacking of the enzyme reaction product.
AB  - In this article, we demonstrate a novel approach to enhancing the sensitivity of
      enzyme-linked immunosorbent assays (ELISA) through pre-concentration of the
      enzyme reaction product (resorufin/4-methylumbelliferone) in free solution. The
      reported pre-concentration was accomplished by transporting the resorufin/4
      methylumbelliferone molecules produced in the ELISA process towards a high ionic
      strength buffer stream in a microfluidic channel while applying a voltage drop
      across this merging region. A sharp change in the electric field around the
      junction of the two liquid streams was observed to abruptly slow down the
      negatively charged resorufin/4-methylumbelliferone species leading to the
      reported pre-concentration effect based on the field amplified stacking (FAS)
      technique. It has been shown that the resulting enhancement in the detectability
      of the enzyme reaction product significantly improves the signal-to-noise ratio
      in the system thereby reducing the smallest detectable analyte concentration in
      the ELISA method. Applying the above-described approach, we were able to detect
      mouse anti-BSA and human TNF-alpha at concentrations nearly 60-fold smaller than
      that possible on commercial microwell plates. For the human TNF-alpha sample,
      this improvement in assay sensitivity corresponded to a limit of detection (LOD)
      of 0.102pg mL(-1) using the FAS based microfluidic ELISA method as compared to
      7.03pg mL(-1) obtained with the traditional microwell plate based approach.
      Moreover, because our ELISAs were performed in micrometer sized channels, they
      required sample volumes about two orders of magnitude smaller than that consumed
      in the latter case (1MUL versus 100MUL).

PMID- 24439503
TI  - Comments on "innovative method for carbon dioxide determination in human
      postmortem cardiac gas samples using headspace-gas chromatography-mass
      spectrometry and stable labeled isotope as internal standard" by Varlet et al.
AB  - Varlet et al. recently proposed a headspace-gas chromatography-mass spectrometry
      (HS-GC-MS) method applicable for the routine determination of CO2 in gaseous
      biologic matrices. This developed bioanalytical method was fully validated
      according to the SFSTP 1997 guidelines using the accuracy profile as a graphical
      decision-making tool.In this letter, we discuss the validity of HS-GC-MS method
      based on the newest SFSTP guideline. In particular, we demonstrate by the
      estimation of the beta-expectation tolerance interval that the error total
      exceeds the acceptance limits (30%) for the second concentration level (0.5MUmol
      mL(-1) vial HS). Furthermore, we show through the risk profile that the
      probability to have future results inside the +/-30% acceptance limits is smaller
      than 95%.

PMID- 24439504
TI  - Response-to-comments about: "Is it really the method for carbon dioxide
      determination in human postmortem cardiac gas samples using Headspace-Gas
      Chromatography-Mass Spectrometry valid?" from T. Saffaj and B. Ihssane.
AB  - Saffaj et al. recently criticized our method of monitoring carbon dioxide in
      human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass
      Spectrometry. According to the authors, their demonstration, based on the latest
      SFSTP guidelines (established after 2007) fitted for the validation of drug
      monitoring bioanalytical methods, has put in evidence potential errors. However,
      our validation approach was built using SFSTP guidelines established before 2007.
      We justify the use of these guidelines because of the post-mortem context of the
      study (and not clinical) and the gaseous state of the sample (and not solid or
      liquid). Using these guidelines, our validation remains correct.

PMID- 24439505
TI  - Targeted analysis of multiple pharmaceuticals, plant toxins and other secondary
      metabolites in herbal dietary supplements by ultra-high performance liquid
      chromatography-quadrupole-orbital ion trap mass spectrometry.
AB  - In this study, an ultra-high performance liquid chromatography-quadrupole-orbital
      ion trap mass spectrometry (UHPLC-Q-orbitrap MS) method was developed and
      validated for simultaneous determination of 96 pharmaceuticals, plant toxins, and
      other plant secondary metabolites in herbal dietary supplements. Target analytes
      were extracted from samples using the QuEChERS (quick easy cheap effective rugged
      safe) procedure. The instrument was operated in full MS-data dependent tandem
      mass spectrometry (full MS-dd-MS/MS) acquisition mode which enabled collection of
      quantitative high resolution (HR) full mass spectral data and confirmatory HR
      MS/MS data in a single run. The method provided excellent selectivity in both
      full MS and dd-MS/MS mode. Under optimized collision energy settings, product ion
      spectra containing both precursor and two or more product ions were obtained for
      most of the analytes. Limits of detection (LODs) and limits of quantification
      (LOQs) for the method differed significantly for the examined matrices.
      LODs<=10MUg kg(-1) and LOQs<=50MUg kg(-1) were obtained for 48 to 81% of target
      compounds across five different matrices. With the exception of highly polar
      analytes, the optimized QuEChERS extraction procedure provided acceptable
      recoveries in the range 70%-120%. The precision of the method, characterized as
      the relative standard deviation (RSD, n=5), was <=25% and <=18% at spiking
      concentrations of 50MUg kg(-1) and 500MUg kg(-1), respectively. Because of
      variations in matrix effects in extracts of herbal dietary supplements that
      differed in composition, the method of standard additions and an approach based
      on dilution of matrix components followed by quantification using solvent
      standards were applied for quantification. The procedure was used to examine
      commercial dietary supplements for the 96 analytes of interest. To the best of
      our knowledge, this is the first report of an integrated analysis and
      quantification of this wide range of compounds.

PMID- 24439506
TI  - Screening for pharmaceutical transformation products formed in river sediment by
      combining ultrahigh performance liquid chromatography/high resolution mass
      spectrometry with a rapid data-processing method.
AB  - While the occurrence of pharmaceuticals in the aquatic environment has been
      extensively investigated, their environmental fate is less thoroughly explored.
      Scarce information on their transformation pathways and transformation products
      (TPs) limits conventional target analytical approaches. In this study, samples
      from water/sediment tests were analyzed by ultrahigh performance liquid
      chromatography interfaced with quadrupole time-of-flight mass spectrometry
      (UHPLC/QToF-MS). A data processing method based on peak detection, time-trend
      filtration and structure assignment was established to provide an efficient way
      for identifying the key TPs in terms of persistence; all software used for the
      individual steps of this method is freely available. The accurate mass and
      meaningful time-trends were major contributors in facilitating the isolation of
      plausible TP peaks. In total, 16 TPs from 9 parent pharmaceuticals were
      identified. Eleven out of the 16 TPs were confirmed by corresponding reference
      standards; no standards were available for the remaining TPs. For additional 6
      potential TPs, a molecular formula was suggested but no additional structural
      information could be generated. Among the TPs identified in the water/sediment
      tests, carbamazepine-10,11-epoxide (parent: carbamazepine), saluamine (parent:
      furosemide), chlorothiazide and 4-amino-6-chloro-1,3-benzenedisulfonamide (parent
      of both: hydrochlorothiazide), and 1-naphthol (parent: propranolol) accumulated
      over the entire incubation period of 35 days. 

PMID- 24439507
TI  - Fluorescent blood glucose monitor by hemin-functionalized graphene quantum dots
      based sensing system.
AB  - In the present work, a highly sensitive and specific fluorescent biosensor for
      blood glucose monitoring is developed based on hemin-functionalized graphene
      quantum dots (GQDs) and glucose oxidase (GOx) system. The GQDs which are simply
      prepared by pyrolyzing citric acid exhibit strong fluorescence and good water
      solubility. Due to the noncovalent assembly between hemin and GQDs, the addition
      of hemin can make hydrogen peroxide (H2O2) to destroy the passivated surface of
      GQDs, leading to significant fluorescence quenching of GQDs. Based on this
      effect, a novel fluorescent platform is proposed for the sensing of glucose.
      Under the optimized conditions, the linear range of glucose is from 9 to 300MUM,
      and the limit of detection is 0.1MUM. As unique properties of GQDs, the proposed
      biosensor is green, simple, cost-efficient, and it is successfully applied to the
      determination of glucose in human serum. In addition, the proposed method
      provides a new pathway to further design the biosensors based on the assembly of
      GQDs with hemin for detection of biomolecules. 

PMID- 24439508
TI  - Characterization of an electrochemical mercury sensor using alternating current,
      cyclic, square wave and differential pulse voltammetry.
AB  - Here we report the characterization of an electrochemical mercury (Hg(2+)) sensor
      constructed with a methylene blue (MB)-modified and thymine-containing linear DNA
      probe. Similar to the linear probe electrochemical DNA sensor, the resultant
      sensor behaved as a "signal-off" sensor in alternating current voltammetry and
      cyclic voltammetry. However, depending on the applied frequency or pulse width,
      the sensor can behave as either a "signal-off" or "signal-on" sensor in square
      wave voltammetry (SWV) and differential pulse voltammetry (DPV). In SWV, the
      sensor showed "signal-on" behavior at low frequencies and "signal-off" behavior
      at high frequencies. In DPV, the sensor showed "signal-off" behavior at short
      pulse widths and "signal-on" behavior at long pulse widths. Independent of the
      sensor interrogation technique, the limit of detection was found to be 10nM, with
      a linear dynamic range between 10nM and 500nM. In addition, the sensor responded
      to Hg(2+) rather rapidly; majority of the signal change occurred in <20min.
      Overall, the sensor retains all the characteristics of this class of sensors; it
      is reagentless, reusable, sensitive, specific and selective. This study also
      highlights the feasibility of using a MB-modified probe for real-time sensing of
      Hg(2+), which has not been previously reported. More importantly, the observed
      "switching" behavior in SWV and DPV is potentially generalizable and should be
      applicable to most sensors in this class of dynamics-based electrochemical
      biosensors. 

PMID- 24439509
TI  - The influence of film morphology and illumination conditions on the sensitivity
      of porphyrins-coated ZnO nanorods.
AB  - ZnO and porphyrins have complementary properties that make their combination
      attractive for diverse applications such as photovoltaic and chemical sensing.
      Among the other features, the organic layer morphology is supposed to influence
      both the chemical sensitivity and the charge transfer processes. In this paper,
      we studied the influence of the film morphology on the sensing properties by
      comparing porphyrins coated ZnO nanorods obtained with two different methods. In
      the first approach, each porphyrin unit is grafted onto preformed ZnO nanorods by
      a carboxylic group as linker. The second method is a one-pot procedure, where ZnO
      nanorods growth occurs in the presence of the water soluble tetrakis-(4
      sulfonatophenyl)porphyrin. In both cases the macrocycles share the same Zn
      tetraphenylporphyrin core structure, but decorated with different peripheral
      groups, necessary to comply with the material growth conditions. The adsorption
      of volatile organic molecules has been monitored measuring the contact potential
      difference between the sensitive surface and a gold electrode, by means of a
      Kelvin probe setup. Sensitive signals have been measured both in dark and under
      visible light. The results show that material preparation affects both the
      sensitivities to gases and light. A chemometric analysis of four sensors (first
      and second growth method, measured in dark and in light) shows two main
      evidences: (a) the interaction between volatile compounds and the sensing layer
      is largely dominated by non-specific dispersion interaction and (b) the signal of
      the four sensors becomes rather uncorrelated when the contribution of the
      dispersion interaction is removed. These results indicate that the differences
      due to film morphology are enough to differentiate the sensor behaviour, even
      when the same porphyrin nucleus is used as sensing element. This feature provides
      an additional degree of freedom for the development of gas sensor arrays. 

PMID- 24439510
TI  - Stable, reproducible, and automated capillary zone electrophoresis-tandem mass
      spectrometry system with an electrokinetically pumped sheath-flow nanospray
      interface.
AB  - A PrinCE autosampler was coupled to a Q-Exactive mass spectrometer by an
      electrokinetically pumped sheath-flow nanospray interface to perform automated
      capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry
      (CZE-ESI-MS/MS). 20ng aliquots of an Escherichia coli digest were injected to
      evaluate the system. Eight sequential injections over an 8-h period identified
      1115+/-70 (relative standard deviation, RSD=6%) peptides and 270+/-8 (RSD=3%)
      proteins per run. The average RSDs of migration time, peak intensity, and peak
      area were 3%, 24% and 19%, respectively, for 340 peptides with high intensity.
      This is the first report of an automated CZE-ESI-MS/MS system using the
      electrokinetically pumped sheath-flow nanospray interface. The results
      demonstrate that this system is capable of reproducibly identifying over 1000
      peptides from an E. coli tryptic digest in a 1-h analysis time. 

PMID- 24439511
TI  - [Biliary cystadenocarcinoma].

PMID- 24439512
TI  - Severe Liver Trauma and Diaphragmatic Rupture in a Bull Running Event.

PMID- 24439513
TI  - Improvements in metabolic abnormalities among overweight schizophrenia and
      bipolar disorder patients.
AB  - PURPOSE: As weight-gain and metabolic abnormalities during treatment with
      psychotropic drugs are of great concern, we evaluated effects of psycho-education
      and medical monitoring on metabolic changes among severely mentally ill patients.
      MATERIALS AND METHODS: During repeated, systematic psycho-education about general
      health among 66 consecutive patients diagnosed with DSM-IV-TR schizophrenia
      (n=33) or type-I bipolar disorder (n=33), we evaluated (at intake 1, 2, 3, and 6
      months) clinical psychiatric status, treatments and doses, recorded physiological
      parameters, and assessed attitudes about medication. RESULTS: At intake, patients
      with schizophrenia vs bipolar disorder were receiving 3-7 times more psychotropic
      medication, with 14% higher initial body-mass index (BMI: 29.1 vs 25.6 kg/m2), 12
      times more obesity, and significantly higher serum lipid concentrations. During 6
      months follow-up, among bipolar disorder patients, polytherapy and serum lipid
      concentrations declined more than among schizophrenia patients (e.g., total
      cholesterol+triglycerides, by 3.21 vs 1.75%/month). BMI remained stable.
      Declining lipid levels were associated with older age, bipolar disorder, being
      unemployed, higher antipsychotic doses, and lower initial BPRS scores (all P <=
      0.001). CONCLUSIONS: Psychotropic treatments were more complex, and metabolic
      measures more abnormal among bipolar disorder than schizophrenia patients.
      Intensive psycho-education, clinical monitoring, and encouragement of weight
      control for six months were associated with improvements in metabolic measures
      (but not to BMI), and more realistic attitudes about medication.

PMID- 24439514
TI  - Poor longitudinal continuity of care is associated with an increased mortality
      rate among patients with mental disorders: results from the French National
      Health Insurance Reimbursement Database.
AB  - BACKGROUND: Research on the impact of the continuity of care (COC) on health
      outcomes in patients with mental illness is limited. This observational study
      examined whether the longitudinal COC is associated with a decreased likelihood
      of death among patients with mental disorders in the French general population.
      METHOD: Data were derived from the French National Health Insurance (NHI)
      reimbursement database. Patients with any mental disorder who visited a
      psychiatrist at least twice within 6 months were included. The primary endpoint
      was death by all causes. We measured longitudinal COC with a psychiatrist twice a
      year between 2007 and 2010, using the COC index developed by Bice and Boxerman.
      The COC index was analysed as a time-dependent variable in a survival analysis
      after adjustments for age, gender and stratifying on comorbidities and social
      status. RESULTS: Among 14,515 patients visiting a psychiatrist at least twice in
      6 months and tracked over 3 years, likelihood of death was significantly lower in
      patients with higher continuity of care (hazard ratio for an increase in 0.1 of
      continuity, adjusted for age, sex, and stratified on comorbidities and social
      status: 0.83 [0.83-0.83]), particularly in those with bipolar disorder, major
      depressive disorder and schizophrenia. CONCLUSION: Improving longitudinal
      continuity of care in mental health care may contribute to substantially decrease
      mortality.

PMID- 24439515
TI  - The relationship between temperament and character and subclinical psychotic-like
      experiences in healthy adults.
AB  - BACKGROUND: Considerable data support phenomenological and temporal continuity
      between psychotic disorders and subclinical psychotic-like experiences (PLE's).
      Although numerous studies have found similar personality correlates for
      schizophrenia and schizotypal personality disorder patients, their unaffected
      first-degree relatives, and healthy adults characterized for schizotypal traits,
      no study has yet investigated personality correlates of PLE's measured by the
      Community Assessment of Psychic Experiences (CAPE). Our study sought to examine
      personality correlates of PLE's using the CAPE in healthy adults. METHOD: The
      CAPE and temperament and character inventory (TCI) were administered to 415
      healthy adults. Regressions examined links between TCI traits and overall PLE
      levels as well as positive and negative PLE's separately. RESULTS: Consistent
      with past studies, lower self-directedness (SD) and reward dependence (RD) and
      higher self-transcendence (ST) and harm avoidance (HA) significantly predicted
      overall PLE levels. Higher ST and persistence (P) and lower SD significantly
      predicted higher levels of positive PLE's while lower SD and RD and higher HA,
      ST, and cooperativeness (C) predicted higher levels of negative PLE's.
      CONCLUSIONS: Associations between TCI and PLE's using the CAPE are strikingly
      similar to past work in non-clinical and patient samples and provide additional
      support for phenomenological continuity between psychotic disorders and sub
      syndromal psychotic symptoms.

PMID- 24439516
TI  - Lower availability of midbrain serotonin transporter between healthy subjects
      with and without a family history of major depressive disorder - a preliminary
      two-ligand SPECT study.
AB  - PURPOSE: Serotonin transporter (SERT) and dopamine transporter (DAT) levels
      differ in patients with major depressive disorder (MDD) who are in a depressed
      state in comparison with healthy controls. In addition, a family history of
      depression is a potent risk factor for developing depression, and inherited
      vulnerability to serotonergic and dopaminergic dysfunction is suspected in this.
      The aim of this study was to examine the availabilities of midbrain SERT and
      striatal DAT in healthy subjects with and without a first-degree family history
      of MDD. METHODS: Eight healthy subjects with first-degree relatives with MDD and
      16 sex- and age-matched healthy controls were recruited. The availabilities of
      SERT and DAT were approximated using SPECT, employing [123I] 2-((2
      ((dimethylamino) methyl) phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc]
      TRODAT-1 as the ligands, respectively. There are missing data for one participant
      with a first-degree family history of MDD from the ADAM study, due to a lack of
      the radio-ligand at the time of experiment. RESULTS: SERT availability in the
      midbrain was significantly lower in subjects with a first-degree family history
      of MDD than in healthy subjects. However, DAT availability was no different
      between two groups. CONCLUSIONS: The results with regard to the midbrain SERT
      level suggest the heritability of MDD.

PMID- 24439518
TI  - Attentional biases toward emotional images in the different episodes of bipolar
      disorder: an eye-tracking study.
AB  - Attentional biases toward emotional information may represent vulnerability and
      maintenance factors in bipolar disorder (BD). The present experimental study
      examined the processing of emotional information in BD patients using the eye
      tracking technology. Bipolar patients in their different states (euthymia, mania,
      depression) simultaneously viewed four pictures with different emotional valence
      (happy, neutral, sad, threatening) for 20s while their eye movements were
      monitored. A group of healthy individuals served as the control. The data
      revealed the following: (i) a decrease in attention to happy images in BD
      patients in their depressive episodes compared to healthy individuals, and (ii)
      an increase in attention to threatening images in BD patients (regardless of
      their episode) relative to the healthy controls. These biases appeared in the
      late stages of information processing and were sustained over the 20s interval.
      Thus, the present findings reveal that attentional biases toward emotional
      information can be a key feature of BD, in that: (i) an anhedonic lack of
      sensitivity to positive stimuli during the bipolar depressive episode may be
      considered a maintaining factor of this clinical state, and (ii) the trait-bias
      toward threat, even in asymptomatic patients, may reflect a marker of
      vulnerability in BD. 

PMID- 24439517
TI  - Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar
      disorder from major depression and schizophrenia and resembles multiple
      sclerosis.
AB  - This study investigated the fatty acid composition of the postmortem superior
      temporal gyrus (STG), a cortical region implicated in emotional processing, from
      normal controls (n=15) and patients with bipolar disorder (BD, n=15), major
      depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative
      purposes, STG fatty acid composition was determined in a separate cohort of
      multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with
      controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in
      the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the
      polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid
      (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the
      monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and
      18:1/18:0 ratios were lower in the STG of BD patients and were inversely
      correlated with total PUFA composition. MS patients exhibited a pattern of fatty
      acid abnormalities similar to that observed in BD patients including elevated
      PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD
      patients exhibit a pattern of fatty acid abnormalities in the STG that is not
      observed in MDD and SZ patients and closely resembles MS patients. 

PMID- 24439521
TI  - Comparative study of the bioaccumulation and elimination of trace metals (Cd, Pb,
      Zn, Mn and Fe) in the digestive gland, gills and muscle of bivalve Pinna nobilis
      during a field transplant experiment.
AB  - The purpose of this study was to investigate the long-term bioaccumulation and
      elimination of Cd, Pb, Mn, Zn and Fe by Pinna nobilis tissues after their 90 day
      transplantation period at Teboulba fishing harbor. During the transplantation
      period, the Cd, Pb, Mn, Zn and Fe concentrations in the different tissues of the
      mussels were measured before and after exposure period. Metal (Cd, Pb, Mn, Zn and
      Fe) accumulation in P. nobilis mussels varied depending on the analyzed tissue
      and the caging times. Notable differences in Cd, Pb, Mn, Zn and Fe accumulation
      patterns within the digestive gland, gills and muscle were found and may be due
      to the ability of each tissue to accumulate metals. During the depuration phase,
      the elimination of Cd, Pb, Mn, Zn and Fe depended on the target tissue and the
      metal speciation. Cd, Pb, Mn and Fe were eliminated rapidly from one organ and
      increased in other when compared to those of 90 day transplanted mussels. The
      increase of metal loads during the elimination phase is not clear and
      particularly what kind of processes is responsible for such response. However, it
      is reasonable to assume that metals increase is related to the existence of an
      accumulation/detoxification mechanism, which involves the transport of metals
      from an organ to another. The data obtained indicate that because of the
      significantly high quantities of Cd, Pb, Mn, Zn and Fe accumulated during the
      exposure phase, the transplanted mussels are suitable bioindicators for
      monitoring trace metals in marine ecosystem. 

PMID- 24439522
TI  - An EEGLAB plugin to analyze individual EEG alpha rhythms using the "channel
      reactivity-based method".
AB  - A recent paper [1] proposed a new technique, termed the channel reactivity-based
      method (CRB), for characterizing EEG alpha rhythms using individual (IAFs) and
      channel (CAFs) alpha frequencies. These frequencies were obtained by identifying
      the frequencies at which the power of the alpha rhythms decreases. In the present
      study, we present a graphical interactive toolbox that can be plugged into the
      popular open source environment EEGLAB, making it easy to use CRB. In particular,
      we illustrate the major functionalities of the software and discuss the
      advantages of this toolbox for common EEG investigations. The CRB analysis
      plugin, along with extended documentation and the sample dataset utilized in this
      study, is freely available on the web at http://bio.dei.unipd.it/crb/. 

PMID- 24439523
TI  - Significance, prognostic value and management of heart rate in hypertension.
AB  - Many epidemiological studies have demonstrated that resting heart rate is a risk
      marker but also a risk factor in patients with coronary artery disease and heart
      failure. In hypertensive subjects free from overt cardiac disease, the question
      has been less frequently addressed. A few cohort studies have shown that
      hypertensive patients with a high resting heart rate have an increased risk of
      all-cause and cardiovascular death. However, intervention trials have not
      demonstrated that lowering the heart rate is beneficial in hypertensive subjects.
      Studies with an assessment of ambulatory heart rate tend to demonstrate a better
      association between cardiovascular outcomes and variables, including nighttime
      heart rate. Clinical trials comparing beta-blockers with non-slowing
      antihypertensive drugs have not demonstrated the superiority of the former.
      Finally, an elevated resting heart rate in hypertensive subjects free from overt
      cardiac disease seems to be more a risk marker than a risk factor. Although these
      patients are at high risk, no scientific data exist to support targeting heart
      rate. In this review, we describe the pathophysiological effects of heart rate,
      including vascular cell signalling, link with sympathetic activity and influence
      on central blood pressure, and the prognostic value and management of HR in
      hypertensive patients free from overt cardiac diseases.

PMID- 24439524
TI  - [Unintended intraoperative extubation in a patient with Treacher Collins
      syndrome: usefullness of GlideScope((r)) videolaryngoscope].

PMID- 24439525
TI  - Health worker exposure risk during inhalation sedation with sevoflurane using the
      (AnaConDa(r)) anaesthetic conserving device.
AB  - INTRODUCTION AND OBJECTIVE: Occupational exposure to sevoflurane should not
      exceed 2 ppm. During inhalation sedation with sevoflurane using the anaesthetic
      conserving device (AnaConDa((r))) in the post-anaesthesia care unit, waste gases
      can be reduced by gas extraction systems or scavenging devices such as
      CONTRAfluranTM. However, the efficacy of these methods has not been clearly
      established. To determine the safest scenario for healthcare workers during
      inhalation sedation with sevoflurane in the post-surgical intensive care unit.
      MATERIALS AND METHODS: An experimental study on occupational exposure was
      conducted in a post-cardiothoracic care unit during March-August 2009. The
      measurements were performed in four post-cardiac surgery sedated adults in post
      surgical intensive care unit and four nurses at the bedside, and at four points:
      scenario A, inhalation sedation without gas extraction system or contrafluran as
      a reference scenario; scenario B, applying a gas extraction system to the
      ventilator; scenario C, using contrafluran; and scenario 0, performing
      intravenous isolation sedation. Sevoflurane concentrations were measured in the
      nurses' breathing area during patient care, and at 1.5 and 8 m from the
      ventilator using diffusive passive monitor badges. RESULTS: All badges
      corresponding to the nurses' breathing area were below 2 ppm. Levels of
      sevoflurane detected using prevention systems were lower than that in the control
      situation. Only one determination over 2 ppm was found, corresponding to the
      monitor placed nearest the gas outlet of the ventilator in scenario A. Trace
      concentrations of sevoflurane were found in scenario 0 during intravenous
      sedation. CONCLUSIONS: Administration of sevoflurane through the AnaConDa((r))
      system during inhalation sedation in post-surgical intensive care units is safe
      for healthcare workers, but gas extraction systems or scavenging systems, such as
      CONTRAfluranTM should be used to reduce occupational exposure as much as
      possible.

PMID- 24439526
TI  - Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances
      Ca2+ clearance from MCF-7 breast cancer cells.
AB  - The expression of the plasma membrane Ca2+ ATPase (PMCA) isoforms is altered in
      several types of cancer cells suggesting that they are involved in cancer
      progression. In this study we induced differentiation of MCF-7 breast cancer
      cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids
      (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13
      acetate (PMA) and found strong upregulation of PMCA4b protein expression in
      response to these treatments. Furthermore, combination of HDACis with PMA
      augmented cell differentiation and further enhanced PMCA4b expression both at
      mRNA and protein levels. Immunocytochemical analysis revealed that the
      upregulated protein was located mostly in the plasma membrane. To examine the
      functional consequences of elevated PMCA4b expression, the characteristics of
      intracellular Ca2+ signals were investigated before and after differentiation
      inducing treatments, and also in cells overexpressing PMCA4b. The increased
      PMCA4b expression - either by treatment or overexpression - led to enhanced Ca2+
      clearance from the stimulated cells. We found pronounced PMCA4 protein expression
      in normal breast tissue samples highlighting the importance of this pump for the
      maintenance of mammary epithelial Ca2+ homeostasis. These results suggest that
      modulation of Ca2+ signaling by enhanced PMCA4b expression may contribute to
      normal development of breast epithelium and may be lost in cancer.

PMID- 24439527
TI  - Activity of nicotinic acid substituted nicotinic acid adenine dinucleotide
      phosphate (NAADP) analogs in a human cell line: difference in specificity between
      human and sea urchin NAADP receptors.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+
      mobilizing second messenger that has been identified. We have previously shown
      that NAADP analogs substituted at the 5-position of nicotinic acid were
      recognized by the sea urchin receptor at low concentration, whereas the 4-
      substituted analogs were not as potent. However, to date the structure-activity
      relationship (SAR) of these analogs has not been addressed in mammalian systems.
      Thus, we asked whether these structurally modified analogs behave similarly in an
      NAADP-responsive mammalian cell line (SKBR3) using microinjection and single cell
      fluorescent imaging methods. Novel "caged" 4- and 5-substituted NAADP analogs
      that were activated inside the cell by flash photolysis resulted in Ca2+
      mobilizing activity in SKBR3 cells in a concentration dependent manner, but with
      reduced effectiveness compared to unmodified NAADP. The SAR in mammalian SKBR3
      cells was quite different from that of sea urchin and may suggest that there are
      differences between NAADP receptors in different species or tissues. Importantly,
      these data indicate that modifications at the 4- and 5-position of the nicotinic
      acid ring may lead to the development of functional photoaffinity labels that
      could be used for receptor localization and isolation in mammalian systems.

PMID- 24439528
TI  - Supporting bachelor of nursing students within the clinical environment:
      perspectives of preceptors.
AB  - Student learning in the clinical environment is a cornerstone of pedagogy for
      students undertaking a Bachelor of Nursing in Australia. METHOD: This paper
      presents the results of a survey that was conducted with registered nurses who
      preceptor students for universities in Australia. FINDINGS: Findings reveal that
      some preceptors do not hold the qualification they are preceptoring students to
      obtain, that university involvement in preparation of preceptors is scant and
      that resource provision and communication from universities to preceptors is
      considered problematic. Registered nurses choose to act as preceptors for reasons
      that are both altruistic and professional. They are often employed in senior
      positions and as such find it difficult to manage time and resolve role conflict.
      CONCLUSION: This paper concludes that the registered nurses who preceptor
      students generally have a positive experience but require greater involvement by
      universities in their preparation, particularly when they are responsible for the
      direct assessment of students. The paper posits this may be best achieved by
      universities creating effective lines of communication and ongoing support. This
      will sustain collaborative and meaningful engagement with registered nurses who
      preceptor undergraduate students.

PMID- 24439530
TI  - Why self-control seems (but may not be) limited.
AB  - Self-control refers to the mental processes that allow people to override
      thoughts and emotions, thus enabling behavior to vary adaptively from moment to
      moment. Dominating contemporary research on this topic is the viewpoint that self
      control relies upon a limited resource, such that engaging in acts of restraint
      depletes this inner capacity and undermines subsequent attempts at control (i.e.,
      ego depletion). Noting theoretical and empirical problems with this view, here we
      advance a competing model that develops a non-resource-based account of self
      control. We suggest that apparent regulatory failures reflect the motivated
      switching of task priorities as people strive to strike an optimal balance
      between engaging cognitive labor to pursue 'have-to' goals versus preferring
      cognitive leisure in the pursuit of 'want-to' goals. 

PMID- 24439529
TI  - Revisiting the role of persistent neural activity during working memory.
AB  - What are the neural mechanisms underlying working memory (WM)? One influential
      theory posits that neurons in the lateral prefrontal cortex (lPFC) store WM
      information via persistent activity. In this review, we critically evaluate
      recent findings that together indicate that this model of WM needs revision. We
      argue that sensory cortex, not the lPFC, maintains high-fidelity representations
      of WM content. By contrast, the lPFC simultaneously maintains representations of
      multiple goal-related variables that serve to bias stimulus-specific activity in
      sensory regions. This work highlights multiple neural mechanisms supporting WM,
      including temporally dynamic population coding in addition to persistent
      activity. These new insights focus the question on understanding how the
      mechanisms that underlie WM are related, interact, and are coordinated in the
      lPFC and sensory cortex. 

PMID- 24439531
TI  - Emphasizing appearance versus health outcomes in exercise: the influence of the
      instructor and participants' reasons for exercise.
AB  - The objectifying nature of exercise environments may prevent women from reaping
      psychological benefits of exercise. The present experiment manipulated self
      objectification through an exercise class taught by an instructor who emphasized
      exercise as either a means of acquiring appearance or health outcomes. The
      purpose of this study was to test for interactions between the class emphasis and
      participants' reasons for exercise (i.e., appearance, health) predicting
      participants' state self-objectification, state social physique anxiety, exercise
      class enjoyment, and future intentions of returning to a similar exercise class.
      Results, obtained via pre- and post-exercise questionnaires, revealed a
      significant interaction between class emphasis and health reasons for exercise
      predicting state self-objectification. Participants with lower health reasons for
      exercise reported greater state self-objectification in the appearance-focused
      class compared to those with higher health reasons for exercise. Adopting
      stronger health reasons for exercise may buffer exercise participants from the
      more objectifying aspects of the group exercise environment. 

PMID- 24439532
TI  - Plasminogen activator inhibitor-1 4G/5G and the MTHFR 677C/T polymorphisms and
      susceptibility to polycystic ovary syndrome: a meta-analysis.
AB  - The aim of this study was to explore whether the plasminogen activator inhibitor
      1 (PAI-1) 4G/5G and the methylenetetrahydrofolate reductase (MTHFR) 677C/T
      polymorphisms are associated with susceptibility to polycystic ovary syndrome
      (PCOS). Meta-analyses were conducted to determine the association between the PAI
      1 4G/5G and MTHFR 677C/T polymorphisms and PCOS using: (1) allele contrast (2)
      homozygote contrast, (3) recessive, and (4) dominant models. For meta-analysis,
      nine studies of the PAI-1 4G/5G polymorphism with 2384 subjects (PCOS, 1615;
      controls, 769) and eight studies of the MTHFR 677C/T polymorphism with 1270 study
      subjects were included. Meta-analysis of all study subjects showed no association
      between PCOS and the PAI-1 4G allele (OR=0.949, 95% CI=0.671-1.343, p=0.767).
      Stratification by ethnicity, however, indicated a significant association between
      the PAI-1 4G allele and PCOS in Turkish and Asian populations (OR=0.776, 95%
      CI=0.602-0.999, p=0.049; OR=1.749, 95% CI=1.297-2.359, p=2.5*10(-5)
      respectively). In addition, meta-analysis indicated an association between PCOS
      and the PAI-1 4G4G+4G5G genotype in Europeans (OR=1.406, 95% CI=1.025-1.928,
      p=0.035). However, meta-analysis of all study subjects showed no association
      between PCOS and the MTHFR 677T allele (OR=0.998, 95% CI=0.762-1.307, p=0.989),
      including Europeans (OR=0.806, 95% CI=0.610-1.063, p=0.126). Meta-analysis showed
      no association between PCOS and the MTHFR 677C/T polymorphism using homozygote
      contrast, and recessive and dominant models. In conclusion, meta-analysis
      suggests the PAI-1 4G/5G polymorphism is associated with susceptibility to PCOS
      in European, Turkish, and Asian populations, but the MTHFR 677C/T polymorphism is
      not associated with susceptibility to PCOS in Europeans. 

PMID- 24439533
TI  - [IgA vasculitis revealing hairy cell leukemia relapse treated by cladribine].

PMID- 24439534
TI  - [Aging of the human testis].
AB  - The morphological and histological changes related to testicular aging are:
      volume decrease, arteriolar sclerosis, degeneration of Leydig cells and Sertoli,
      depletion of germ cells and thickening of the tunica albuginea testis. The
      participation in testicular androgen decline in aging is related to the decrease
      in the number of Leydig cells associated with alterations in the functioning of
      the hypothalamic-pituitary axis Sperm volume, concentration and total number,
      motility and morphology of sperm decrease with aging male. The interindividual
      variability of sperm parameters, the variability of methodologies for data
      collection and selection of patients must be careful in interpreting the
      published results. Overall, the quality of sperm decreases progressively with
      age, without any age limit that can be individualized. Alterations of
      spermatogenesis do not seem significantly compromising fertility in the elderly.
      The clinical impact of testicular aging implies androgen production decrease and
      diseases associated with aging. 

PMID- 24439535
TI  - [Advance nursing in France: "a new hope"?].

PMID- 24439536
TI  - [Gonadal function and male reproduction].

PMID- 24439537
TI  - [Spigelian hernias].
AB  - Spigelian hernias represent 1-2% of all abdominal wall hernias. The pathogenesis
      often involves a dehiscence of the transverse and internal oblique muscle
      aponeurosis. The diagnosis is made by physical examination; but sometimes it is
      complicated by obesity. The risk of strangulation is important and can reach 30%.
      The abdominal CT scan is helpful in the description of hernia's topography and
      sometimes in diagnostic confirmation. The treatment is surgical. The rate of
      recurrence after direct closure is considerable. Synthetic mesh repair seems to
      be a more adequate alternative. The advent of laparoscopy has improved the
      management of these hernias. 

PMID- 24439538
TI  - [Biliary cyst of the hepatic left lobe: A case report in Madagascar].

PMID- 24439539
TI  - [Fertility in Klinefelter syndrome].
AB  - In Klinefelter syndrome with non-mosaic 47,XXY caryotype, a biological paternity
      can be obtained by TEsticular Sperm Extraction and Intra-Cytoplasmic sperm
      injection (TESE-ICSI). TESE is positive in about 50 % of the cases in published
      series of non-mosaic 47,XXY Klinefelter syndrome. Age is the main prognosis
      factor for TESE. Among patients seeking children, the percentage of positive TESE
      is higher in younger men. Sperm cells are extracted from focal spermatogenesis.
      They differenciate from spermatogonia which have corrected their chromosome
      complement (46,XY). The risk of aneuploidy is similar in Klinefelter syndrome and
      in non-obstructive azoospermia with normal caryotype. Among more than 100 born
      children reported in the literature, all have a normal caryotype. Only one
      foetus, within a triple pregnancy, had a 47,XXY caryotype. Whether the percentage
      of positive TESE is better for adolescent than for adult Klinefelter patients
      should be addressed by performing a TESE in adolescent (from 15 years old)
      similarly to adult Klinefelter patients. TESE will be followed by
      cryopreservation of extracted sperms. They will be used latter for ICSI when the
      patient will seek children. This early TESE can be performed before the beginning
      of the androgenic treatment, avoiding the potential deleterious feedback effect
      of exogenous testosterone on the gonadotropin secretion and on the focal
      spermatogenesis. Any androgenic treatment should be interrupted at least six
      months before the TESE to avoid the feedback lowering effect on gonadotropin
      secretion.

PMID- 24439540
TI  - [Hypoandrogenism in aging men: criteria? Mechanism? For whom?].

PMID- 24439541
TI  - [Psychiatry in 2030?].

PMID- 24439542
TI  - Downmodulation of peripheral MOG-specific immunity by pVAXhsp65 treatment during
      EAE does not reach the CNS.
AB  - Most of the therapeutic strategies to control multiple sclerosis are directed to
      immune modulation and inflammation control. As heat shock proteins are able to
      induce immunoregulatory T cells, we investigated the therapeutic effect of a
      genetic vaccine containing the mycobacterial hsp65 gene on experimental
      autoimmune encephalomyelitis (EAE). Although pVAXhsp65 was immunogenic for mice
      with EAE and downmodulated specific cytokine induction by MOG, therapy was not
      able to decrease clinical severity nor to modify immunologic parameters in the
      CNS. These results indicate that hsp65, administered as a DNA vaccine, was not
      therapeutic for EAE. 

PMID- 24439543
TI  - Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy.
AB  - We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring
      serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old
      woman was admitted to our hospital because of dyspnea and sore throat diagnosed
      as pharyngitis 1 week before admission. On admission, the sore throat had
      exacerbated and dyspnea developed. She had history of atrial fibrillation, for
      which warfarin 1.5 mg/d was started approximately 10 years prior and her
      international normalized ratio (INR) had been maintained at an acceptable
      therapeutic level. Blood results revealed unmeasurable INR and abnormally
      prolonged activated partial thromboplastin time (APTT). She was diagnosed with
      adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20
      mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the
      coagulopathy responded to intravenous VK administration, the patient was
      clinically diagnosed with warfarin-related relative VKD. Approximately 1 month
      later, she returned with complaints of sore throat. Blood results indicated
      abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent
      adenoiditis and VK deficient coagulopathy. The patient's serum VK levels were low
      (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg)
      and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated.
      Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in
      patients undergoing warfarin therapy is primarily caused by, relative VKD.
      However, the possibility of warfarin-related absolute VKD should be suspected
      when INRis not sufficiently improved by intravenous VK administration.

PMID- 24439544
TI  - Senior patients with moderate to severe pain wait longer for analgesic medication
      in EDs.
AB  - STUDY OBJECTIVE: Delayed pain treatment is a common problem in emergency
      departments (EDs). The objective of this study was to examine the effect of age
      on time to ED patients receiving the first analgesic dose for moderate to severe
      pain. METHODS: Real-time, archived data from a tertiary urban hospital and a
      secondary regional hospital were analyzed post hoc. We included all consecutive
      adult ED patients (>= 18 years) on stretchers whose pain intensity was at least 4
      (0-10, verbal numerical scale) at triage between March 2008 and December 2012.
      The primary outcome was time from the beginning of triage to analgesic medication
      in seniors (>= 65 years) compared with younger patients. RESULTS: A total of
      34,213 patients (56% women) were triaged to an ED bed with mean pain intensity of
      7.6 (SD +/- 1.8). Analgesics were administered to 20,486 patients (59.9%) in a
      median time of 2.3 hours (interquartile range [IQR] = 3.6). Median time for
      seniors to receive analgesics was 3.2 hours (IQR = 5.1) compared with 2.1 hours
      (IQR = 3.1, effect size = 0.19) for younger patients. This represents a 55.2%
      increase in time to analgesic for seniors. Seniors waited 12 minutes longer to be
      evaluated by a physician, 20 minutes longer for analgesic prescription, and 35
      minutes longer for medication administration. After controlling for confounding
      factors, they still waited longer to receive pain medication (hazards ratio =
      1.37; 95% confidence interval, 1.32-1.42) than younger patients. CONCLUSION:
      Seniors with moderate to severe pain wait 1.1 hours (55.2%) longer than younger
      patients to receive analgesics. Physicians and nurses (32 and 35 minutes,
      respectively) contributed to this disparity.

PMID- 24439545
TI  - Primary umbilical endometriosis presenting as umbilical drainage in a nulliparous
      and surgically naive young woman.
AB  - Endometriosis is well known as a chronic condition associated with significant
      morbidity. Umbilical endometriosis, however, may go unrecognized because of its
      rarity, leading to multiple medical visits and a delayed diagnosis. Chronic
      umbilical drainage is an unusual presentation for umbilical endometriosis. Even
      more unusual is the development at this location in a patient without previous
      abdominal surgery. There are very few published case reports about primary
      umbilical endometriosis. A 24-year-old nulliparous African American woman
      presents to the emergency department with a complaint of chronic umbilical
      drainage of 3-year duration and undergoes a computed tomographic scan and
      subspecialty referral, which lead to the diagnosis of primary abdominal wall
      endometriosis and a new left ovary endometrioma. Although this is an unusual
      occurrence, it may be considered in patients with chronic umbilical drainage
      without other cause.

PMID- 24439546
TI  - A new formal perspective on 'Cambrian explosions'.
AB  - The 'Cambrian explosion' 500 Myr ago saw a relatively sudden proliferation of
      organism Bauplan and ecosystem niche structure that continues to haunt
      evolutionary biology. Here, adapting standard methods from information theory and
      statistical mechanics, we model the phenomenon as a noise-driven phase
      transition, in the context of deep-time relaxation of current path-dependent
      evolutionary constraints. The result is analogous to recent suggestions that
      multiple 'explosions' of increasing complexity in the genetic code were driven by
      rising intensities of available metabolic free energy. In the absence of severe
      path-dependent lock-in, 'Cambrian explosions' are standard features of blind
      evolutionary process, representing outliers in the ongoing routine of
      evolutionary punctuated equilibrium.

PMID- 24439547
TI  - Characterization of ten date palm (Phoenix dactylifera L.) cultivars from Saudi
      Arabia using AFLP and ISSR markers.
AB  - Date palm is the most economically important plant in the Middle East due to its
      nutritionally valuable fruit. The development of accurate DNA fingerprints to
      characterize cultivars and the detection of genetic diversity are of great value
      for breeding programs. The present study explores the usefulness of ISSR and AFLP
      molecular markers to detect relationships among 10 date palm (Phoenix dactylifera
      L.) cultivars from Saudi Arabia. Thirteen ISSR primers and six AFLP primer
      combinations were examined. The level of polymorphism among cultivars for ISSRs
      ranged from 20% to 100% with an average of 85%. Polymorphism levels for AFLPs
      ranged from 63% to 84% with an average of 76%. The total number of cultivar
      specific markers was 241, 208 of which were generated from AFLP analysis. AJWA
      cultivar had the highest number of cultivar-specific ISSR markers, whereas DEK,
      PER, SUK-Q, SHA and MOS-H cultivars had the lowest. RAB and SHA cultivars had the
      most and least AFLP cultivar-specific markers, respectively. The highest pairwise
      similarity indices for ISSRs, AFLPs and combined markers were 84% between DEK
      (female) and PER (female), 81% between SUK-Q (male) and RAB (male), and 80%
      between SUK-Q (male) and RAB (male), respectively. The lowest similarity indices
      were 65% between TAB (female) and SUK-Q (male), 67% between SUK-A (female) and
      SUK-Q (male), and 67% between SUK-A (female) and SUK-Q (male). Cultivars of the
      same sex had higher pairwise similarities than those between cultivars of
      different sex. The Neighbor-Joining (NJ) tree generated from the ISSR dataset was
      not well resolved and bootstrap support for resolved nodes in the tree was low.
      AFLP and combined data generated completely resolved trees with high levels of
      bootstrap support. In conclusion, AFLP and ISSR approaches enabled discrimination
      among 10 date palm cultivars of from Saudi Arabia, which will provide valuable
      information for future improvement of this important crop. 

PMID- 24439549
TI  - Characterization of the aap1 gene of Agaricus bisporus, a homolog of the yeast
      YAP1.
AB  - The structure, homologies, polymorphism and expression profiles of a new gene,
      aap1, have been studied for precisely characterizing it and defining its putative
      involvement in thermo-tolerance of both vegetative mycelium growth and sporophore
      differentiation. Sequence polymorphism was analyzed in 3 homokaryons of A.
      bisporus and 24 strains having different abilities for mycelial growth at
      temperatures above 30  degrees C and for producing mature fruiting bodies at 25 
      degrees C. The level of gene expression was measured by real-time PCR both in
      vegetative mycelium after transfer from 25 to 32  degrees C and in primordia and
      fruiting bodies produced during cultures at 17 or 25  degrees C. The results
      indicated that aap1 gene belong to a new subfamily of the yeast YAP1 homologs. It
      is not a dominant contributor to the thermo-tolerance of A. bisporus, but the
      protein it encodes may be involved as an overall stress resistance transcription
      factor. The way Aap1 senses redox level differs from that of AP-1-like
      transcription factor Yap1.

PMID- 24439548
TI  - Effect of reverse photoperiod on in vitro regeneration and piperine production in
      Piper nigrum L.
AB  - In this study, a novel approach for in vitro regeneration of Piper nigrum L. has
      been applied in order to increase healthy biomass, phytochemicals and piperine
      production via reverse photoperiod (16hD/8hL). Leaf portions of the seed-derived
      plants were placed on an MS-medium fortified with different PGRs. Under 16hD/8hL,
      thidiazuron (TDZ; 4.0 mg L-1) and BA (1.5 mg L-1) was found to be the most
      effective (<90%) in callus induction. Two concentrations (1.5, 2.0 mg L-1) of the
      IBA produced>80% shoots from callus cultures. Healthy shoots were transferred to
      rooting medium and higher percentage of rooting (<90%) was observed on IBA (1.5
      mg L-1). These in vitro tissues were subjected to amino acid analysis,
      spectrophotometry, and HPLC. ARG, SER, THR, and TYR were the most abundant
      components out of 17 amino acids. Higher amino acid production was observed under
      normal photoperiod (16hL/8hD) than under reverse photoperiod (16hD/8hL). The
      highest total phenolic content (TPC; 9.91 mg/g-DW) and flavonoid content (7.38
      mg/g-DW) were observed in callus cultures incubated under 16hL/8hD than other
      tissues incubated under 16hD/8hL photoperiod. Higher DPPH and PoMo activities
      were observed in tissues incubated under 16hL/8hD photoperiod, while ABTS and
      Fe2+ chelating activities were found higher in tissues incubated under reverse
      photoperiod. Significant quantities of piperine content were observed in all
      tissues except callus cultures. These results suggest that reverse photoperiod is
      a promising approach for callus induction, phytochemicals and piperine production
      for commercial applications.

PMID- 24439550
TI  - [Contents of macromineral and trace elements in spirulina (Arthrospira platensis)
      from France, Chad, Togo, Niger, Mali, Burkina-Faso and Central African Republic].
AB  - Data on mineral elements in spirulinas being limited, we analyzed macrominerals
      and trace elements of samples from France and Africa. Spirulinas cultivated in
      France have a composition in macromineral elements similar to those of the
      literature. The entire contents of trace elements are low. Unlike marine
      cyanobacteria, they do not concentrate rare-earth elements. Spirulina harvested
      in Chad has high levels in macrominerals and trace elements, due to traditional
      drying and harvesting methods. Rare-earth element levels are attributed to this
      pollution and not to their concentration in spirulinas, because rare-earth
      element normalized profiles of spirulina are strictly parallel to those of ouadis
      mud and very different from those of ouadis water. Despite the sometimes high
      content of total As, normal water consumption in Chad presents no health
      problems. Spirulinas grown in Togo, Niger, Mali, Burkina-Faso and Central African
      Republic have chemical compositions similar to those of Chad spirulinas, but with
      a lower content of macromineral and trace elements, reflecting a lower mineral
      pollution. Rare-earth element normalized patterns dismiss an aeolian pollution
      and the pollution is rather of pedological origin. They show no toxicity problem
      except spirulinas from Burkina-Faso, whose Pb content is too high. The
      variability of composition of spirulinas can be largely attributed to the mineral
      pollution of the samples. Significant levels of rare-earth elements sometimes
      found in the literature reflect this pollution. 

PMID- 24439551
TI  - Prey selection by nesting House Martins Delichon urbica Linne, 1758 (Aves:
      Hirundinidae) in Algiers suburbs (Algeria).
AB  - The diet of the House Martin Delichon urbica was analyzed in a suburban area in
      Pins maritimes, northeast of Algiers (Algeria). The diet was determined by
      analyzing 120 faecal samples collected from a breeding colony between April and
      September 2007. Insects were the most numerous prey types (99.86%). Hymenopterans
      were the dominant preys (56.99%), followed by Coleopterans (20.14%), Homopterans
      (14.22%), Heteropterans (5.45%), and Dipterans (3.10%). Division of the prey
      items into families demonstrated that the highest relative frequency was large
      Hymenopterans in the family Formicidae (54.0%). The dominant species in the diet
      was Tetramorium biskrensis, which comprised 32.6% of the diet. It was followed by
      Camponotus barbaricus (6.9%) and Monomorium salomonis (5.6%). Comparison between
      diet and availability of preys using the Savage index showed that T. biskrensis,
      Crematogaster scutelaris, Pheidole pallidula, Diptera sp. unident. and Aphidae
      sp. unident. were positively selected by D. urbica. 

PMID- 24439552
TI  - Seed development in Malpighiaceae species with an emphasis on the relationships
      between nutritive tissues.
AB  - Malpighiaceae ovules have a well-developed nucellus; previous observations
      indicate that during seed development, the endosperm does not proliferate, thus,
      remaining scarce. This study aimed at identifying the nutritive tissues during
      seed development in Malpighiaceae, focusing especially on the endosperm. We
      analysed the seed development of Janusia mediterranea, J. occhionii, Mascagnia
      cordifolia, and Tetrapterys chamaecerasifolia, which were collected and processed
      by traditional methods for light microscopy. Ovules are subcampylotropous,
      crassinucellate and unitegmic in Janusia and bitegmic in M. cordifolia and T.
      chamaecerasifolia. The nucellus is well developed and protrudes through the
      micropyle, touching the funicular obturator. During development, a pachychalaza
      is formed, and the integuments coalesce in bitegmic species. Through a series of
      nucellar cell divisions, the perisperm is formed. In Janusia species, the
      endosperm is not produced. In M. cordifolia and T. chamaecerasifolia, the
      endosperm is nuclear, but it is scarce and ephemeral. The mature seed is
      exalbuminous, and the perisperm is consumed, and thus, the mature embryo is
      total. The absence of endosperm in Janusia is newly observed for the family and
      indicates functional transfer for the abundant perisperm. 

PMID- 24439553
TI  - Is there a flame in the brain in psychosis?

PMID- 24439554
TI  - Immunologic therapeutics and psychotic disorders.

PMID- 24439556
TI  - [Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in
      combination in France: description according to the 2009 ILAE definition of AED
      resistance (ESPERA study)].
AB  - AIMS: To describe the adult population treated with antiepileptic drugs (AEDs) in
      combination for focal epilepsy according to the definition of AED resistance
      proposed by the International League Against Epilepsy (ILAE) in 2009 and to
      evaluate its implementation in current practice. METHODS: ESPERA was a
      multicenter, observational, cross-sectional study with a clinical data collection
      covering the past 12 months conducted by neurologists. Classifications according
      to AED responsiveness established by investigators for each enrolled patient were
      revised by two experts. RESULTS: Seventy-one neurologists enrolled 405 patients.
      Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the
      investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3%
      had an undefined drug-responsiveness. After revision of experts, 71% of
      epilepsies were classified as drug resistant, 22% as responsive and 7% as
      undefined. Among the participating neurologists, 76% have made at least one error
      in classifying their patients according to the 2009 ILAE definition of AED
      resistance. Because of epilepsy, 24% of patients (age<=65) were inactive and 42%
      could not drive (respectively 29 and 49% of patients with AED resistant
      epilepsy). Half of patients had at least one other chronic condition. Number of
      prescribed drugs in combination and health care resource utilisation were
      significantly higher in patients with drug-resistant epilepsies than in patients
      with drug responsive epilepsies. CONCLUSION: ESPERA study shows that the use of
      new definition of drug-resistance in everyday practice seems difficult without
      any additional training and that the social and professional disability is
      frequent in adults with focal epilepsies treated with polytherapy.

PMID- 24439557
TI  - More on the clinical usefulness of Oscillococcinum.

PMID- 24439555
TI  - The cytokine model of schizophrenia: emerging therapeutic strategies.
AB  - We discuss the rationale for a trial of a novel biological immunotherapy in
      schizophrenia (SCZ). Available antipsychotic treatments for SCZ are often limited
      by partial effectiveness and significant side effects. The search for novel
      medications is of high priority. All current antipsychotics function primarily by
      blocking D2-type dopamine receptors. An emerging theory of SCZ postulates
      disturbances of cytokines and inflammatory mediators (i.e., the cytokine model),
      possibly originating in part from infectious exposures. Cytokines are one of the
      most important components of the immune system that orchestrate the response to
      infectious and other exogenous insults. Preclinical models of SCZ support a
      convergence between a role for certain cytokines in the pathophysiology of SCZ
      and major neurochemical postulates of the disorder, including the dopamine and
      glutamate hypotheses. Several cytokines are elevated in plasma in SCZ, and
      positron emission tomography studies have shown active inflammation in the brains
      of patients with psychosis. Treatment studies of anti-inflammatory agents, such
      as celecoxib and aspirin, in patients with SCZ have provided further support for
      neuroinflammation in this disorder. The development of approved biological
      therapies for autoimmune diseases provides new opportunities to target cytokine
      signaling directly as a novel treatment strategy in SCZ. In addition, advances in
      imaging, immunology, and psychopharmacology have paved the way for using measures
      of target engagement of neuroimmune components that would facilitate the
      identification of patient subgroups who are most likely to benefit from cytokine
      modulation. 

PMID- 24439558
TI  - Defensive functioning in MtF and FtM transsexuals.
AB  - In spite of the potential clinical utility of defense mechanisms in the
      assessment of gender identity disorder patients as candidates to sex reassignment
      surgery, there is paucity of research in this field. The aim of the present study
      is therefore to ascertain whether the defensive profile of MtF and FtM
      transsexuals seeking sex reassignment surgery can be defined more primitive,
      immature and maladaptive than that of the two control groups. We compared the
      defensive profiles as assessed through the REM-71 (Steiner et al., 2001) of 104
      MtF transsexuals, 46 FtM transsexuals and two control groups of males and
      females. Our results show that MtF transsexuals present an overall more primitive
      defensive array than that of both control groups, while FtMs show a profile not
      dissimilar from that of both control groups. Our results support the hypothesis
      that MtF transsexuals are characterized by higher proneness to psychopathology
      than the general population and show a more immature level of psychological
      functioning than FtM transsexuals. 

PMID- 24439559
TI  - Distress intolerance in substance dependent patients.
AB  - This study seeks to extend the literature by examining distress tolerance (DT)
      levels for a substance dependent group of individuals. Next, it considers the
      potential relationship of DT levels with substance dependence features and
      finally, it compares those factors with a healthy control group. This study
      included 93 individuals (49 substance dependent and 44 healthy controls).
      Participants were evaluated using the Structured Clinical Interview for DSM-IV
      Axis I Diagnosis (SCID-I) and given the Distress Tolerance Scale (DTS), Beck
      Depression Inventory (BDI), and State & Trait Anxiety Inventory (STAI).
      Consistent with our expectations, the substance dependent group showed higher
      scores on the BDI and STAI, and lower scores on the DTS. There was no difference
      between the single drug dependent group and multiple substance-dependent groups,
      and their DT levels were not correlated with the duration of substance use, nor
      with the age of first substance use. Instead, DT was strongly correlated with
      trait anxiety, state anxiety, and depressive symptoms. The DT levels of this
      group of substance dependent individuals were very low in comparison to controls
      and to other groups reported in the literature. Our results suggest that distress
      tolerance may represent a therapeutic target factor in substance dependency
      treatment. Limitations and future research directions are also discussed. 

PMID- 24439560
TI  - Assessing alexithymia and emotional awareness: relations between measures in a
      German non-clinical sample.
AB  - The aim of this study was to evaluate psychometric properties and relations
      between two different methods of measuring alexithymia and one measure of
      emotional awareness in a German non-clinical sample. The 20-Item Toronto
      Alexithymia Scale (TAS-20), the Toronto Structured Interview for Alexithymia
      (TSIA), and the Levels of Emotional Awareness Scale (LEAS), which is a
      performance-based measure of emotional awareness, were administered to 84
      university students. Both internal reliability and inter-rater reliability for
      the TSIA were acceptable. Results from exploratory factor analysis (EFA) based on
      all measures supported a three factorial solution previously obtained in an
      American sample using multiple methods of alexithymia and emotional ability
      measurement. In our three factor model direct self (TAS-20), direct other (TSIA),
      and indirect self (LEAS) measures were differentiated. The convergent validity of
      the TSIA was supported by a significant correlation with the LEAS. Our findings
      suggest that future research on alexithymia and emotional awareness can benefit
      from the use of a multi-method approach and should include objective measures. 

PMID- 24439561
TI  - The TAS-20 more likely measures negative affects rather than alexithymia itself
      in patients with major depression, panic disorder, eating disorders and substance
      use disorders.
AB  - BACKGROUND: This study evaluates whether the difference in Toronto Alexithymia
      Scale-20 item (TAS-20) between patients with major depression (MD), panic
      disorder (PD), eating disorders (ED), and substance use disorders (SUD) and
      healthy controls persisted after controlling for the severity of anxiety and
      depression. METHODS: Thirty-eight patients with MD, 58 with PD, 52 with ED, and
      30 with SUD and 78 healthy controls (C) completed the TAS-20, the Hamilton Rating
      Scale for Anxiety (Ham-A), the Hamilton Rating Scale for Depression (Ham-D).
      RESULTS: The differences in TAS-20 scores observed between patient groups,
      regardless of the type of their disorders, and controls disappeared after
      controlling for the effect of anxiety and depression severity. In contrast, the
      differences in severity of anxiety and depression between patients and controls
      were still present, after excluding the effect of alexithymic levels.
      CONCLUSIONS: Our data suggest that alexithymic levels, as measured by the TAS-20,
      are modulated by the severity of symptoms, supporting the view that alexithymia
      can represent a state phenomenon in patients with MD, PD, ED and SUD, because the
      TAS-20 seems overly sensitive to a general distress syndrome, and it is more
      likely to measure negative affects rather than alexithymia itself.

PMID- 24439562
TI  - Prognostic implications of paranoia and thought disorder in new onset psychosis.
AB  - This study follows a group of 174 young people with new onset of schizotypal
      symptoms and examines factors which may lead to conversion to psychosis. These
      prodromal subjects were screened for symptoms and later given the Structured
      Clinical Interview of DSM-III-R at one year, two years and ten years post onset.
      We also included the Paranoia Scale of Fenigstein and Vanable and the Scale for
      Thought, Language and Communications of Andreasen in all interviews. Our analysis
      found that the addition of scales for paranoia and thought disorder enhanced
      prediction of conversion to psychosis and long term outcome. The early occurrence
      of ideas of reference and poverty of thought appear to be significant predictors
      of future deterioration even when considered among other high-risk variables. 

PMID- 24439563
TI  - EOS analysis of lower extremity segmental torsion in children and young adults.
AB  - INTRODUCTION: Lower limb torsion varies substantially among healthy children
      during growth. Values reported in the literature to date have been obtained using
      semi-quantitative clinical or 2D measurement methods. Quantitative 3D measurement
      would help determine the physiological range of lower limb torsion. Low-dose
      stereoradiography with 3D reconstruction provides a good alternative. Its use
      increases in pediatrics because of radiation minimization. Previous studies have
      shown accurate and reproducible results of lower limbs reconstruction in adults
      and children but the torsional parameters haven't been measured yet. The present
      study reports the values of lower limb segmental torsion and its course during
      growth in a cohort of healthy children and young adults using the EOS low-dose
      biplanar X-ray. HYPOTHESIS: EOS 3D reconstruction is an accurate and reproducible
      method to measure the torsional parameters in children. MATERIALS AND METHODS:
      Femoral torsion (FT) and tibial torsion (TT) were studied on 114 volunteers (228
      lower limbs) from 6 to 30 years of age divided by age into 5 groups. The EOSTM
      acquisitions were obtained in subjects standing with their feet offset. RESULTS:
      Mean FT decreased during growth, passing from 21.6 degrees  to 18 degrees ,
      whereas mean TT increased from 26.8 degrees  to 34.7 degrees . There was a
      statistically significant difference between the 2 extreme age groups, but no
      difference was found between any other age groups. The ICC for intra-observer
      reproducibility was 0.96 and 0.95 for FT and TT for the first operator, and 0.79
      and 0.83 for the second operator respectively. The ICC for inter-observer
      reproducibility was 0.84 and 0.82 respectively. DISCUSSION: The course of lower
      limb segmental torsion observed was consistent with literature reports based upon
      clinical and 2D measurements. 3D reconstruction of EOS low-dose biplanar imaging
      appears to be a safe and reliable tool for lower limbs measurements, especially
      for investigating lower limb segmental torsion in children and adults. LEVEL OF
      EVIDENCE: Level IV.

PMID- 24439564
TI  - The challenge of the 'C' in CML.

PMID- 24439565
TI  - Cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) compared to
      standard induction in acute myeloid leukemia from myelodysplastic syndrome after
      azanucleoside failure.
AB  - For patients with acute myeloid leukemia from antecedent myelodysplastic syndrome
      particularly after azanucleoside treatment failure, outcome is poor. Here, we
      conducted a case-control study in these patients to compare the efficacy of CLAG
      M induction (28 patients) versus standard 3+7 induction chemotherapy (24
      patients). Response rates (P=0.014) and median overall survival (P=0.025) were
      64% and 202 days (95% CI 37-367 days) versus 29% and 86 days (95% CI 36-136) in
      the CLAG-M and 3+7 cohorts, respectively. Median overall survival was 202 (95% CI
      37-367 days) versus 86 days (95% CI 36-136) (P=0.025), respectively. CLAG-M has
      encouraging activity in this patient group. 

PMID- 24439566
TI  - Proposal for refining the definition of dysgranulopoiesis in acute myeloid
      leukemia and myelodysplastic syndromes.
AB  - Studies of morphology of myelodysplastic syndromes (MDS) or acute myeloid
      leukemia (AML) refer to the definitions produced by the French-American-British
      (FAB) group and by the World Health Organization expert group. To clarify some
      points regarding the dysgranulopoiesis that are still unclear we analyzed a
      series of 98 neutrophils from MDS patients with regard to granularity, nuclear
      segmentation, the appearance of the chromatin, the presence of giant neutrophils,
      and the presence of nuclear chromatin extensions. We found that cells with at
      least 2/3 reduction of the content of granules, Pelger-like neutrophils,
      dysplastic non-Pelger cells, neutrophils with abnormal clumping of the chromatin,
      and macropolycytes could be recognized as dysplastic and included in the 10%
      count recommended by these two classifications. In addition, we suggest that
      neutrophils with more than 4 nuclear projections could be recognized as a
      relevant dysplastic feature. 

PMID- 24439567
TI  - The lower peripheral blood lymphocyte/monocyte ratio assessed during routine
      follow-up after standard first-line chemotherapy is a risk factor for predicting
      relapse in patients with diffuse large B-cell lymphoma.
AB  - A specific predictor during routine follow-up to ascertain risk for relapse after
      standard first-line chemotherapy in non-Hodgkin's lymphoma (NHL) has not been
      identified, although blood counts, lactate dehydrogenase (LDH) and imaging
      studies, such as computed tomography (CT) scans or positron emission tomography,
      have been recommended. Therefore, we studied the absolute lymphocyte
      count/absolute monocyte count ratio (ALC/AMC ratio) as a marker of poststandard
      first-line chemotherapy for predicting relapse in patients with diffuse large B
      cell lymphoma (DLBCL). 220 consecutive DLBCL patients, originally diagnosed,
      treated with CHOP or R-CHOP and followed up at two institutions. ALC/AMC ratio
      was obtained at the time of confirmed relapse or last follow-up. Patients at the
      time of confirmed relapse (n = 163) had a lower ALC/AMC ratio compared with those
      at last follow-up (n = 57) (P < 0.001). ALC/AMC ratio at the time of confirmed
      relapse was a strong predictor for relapse with an area under the curve = 0.813
      (P < 0.001). The sensitivity and specificity for ALC/AMC ratio at the time of
      confirmed relapse or at last follow-up were 68.1% and 87.7%, respectively, and
      the relative risk of relapse with an ALC/AMC ratio < 2.8 at the time of confirmed
      relapse or at last follow-up was 1.845 with an odds ratio of 15.247 (95%
      cumulative incidence: 6.473-35.916) after CHOP or R-CHOP in DLBCL. Patients with
      an ALC/AMC ratio (< 2.8) had a higher cumulative hazard rate of relapse compared
      with an ALC/AMC ratio (>=2.8) (P < 0.001). This study suggests that the lower
      ALC/AMC ratio can be used as a marker to assess risk of DLBCL relapse during
      routine follow-up after standard first-line chemotherapy.

PMID- 24439568
TI  - Analytical performance of the cobas EGFR mutation assay for Japanese non-small
      cell lung cancer.
AB  - INTRODUCTION: Clinical outcomes in non-small-cell lung cancer (NSCLC) patients
      with epidermal growth factor receptor (EGFR) mutations have been reported to be
      correlated with the use of EGFR-tyrosine kinase inhibitors (EGFR-TKIs).
      Therefore, it is essential to confirm the presence of EGFR mutations using highly
      sensitive testing methods. In this study, we compared the performance of the
      cobas((r)) EGFR Mutation Test (cobas EGFR assay) and the therascreen((r)) EGFR
      RGQ PCR Kit (therascreen EGFR assay) for use as an in vitro diagnostic (IVD)
      product. METHODS: We extracted DNA from 150 formalin-fixed, paraffin-embedded
      tissue samples from 150 patients diagnosed with NSCLC, and performed a
      comparative study of the cobas EGFR and therascreen EGFR assay methods. All
      discordant results were re-analyzed by direct sequencing. RESULTS: The
      concordance rate between the cobas EGFR assay and the therascreen EGFR assay was
      98.0% (145/148). EGFR mutations were detected at a frequency of 40.9% (61/149) in
      NSCLC specimens using the cobas EGFR assay and 40.2% (60/149) using the
      therascreen EGFR assay. Three discrepant results were found in this study. Two
      double mutations were detected by the cobas EGFR assay but only one in the
      therascreen EGFR assay. No invalid results resulted from sample analysis by the
      cobas EGFR assay. CONCLUSIONS: Our results show a high concordance rate (98.0%)
      of cobas EGFR assay with an existing IVD product, the therascreen EGFR assay.
      Since they are IVD diagnostic products, both assays proved to be simple,
      validated methods in detecting the most common, clinically significant EGFR
      mutations and proved to be helpful for appropriate treatment guidance for NSCLC
      patients.

PMID- 24439569
TI  - Does KRAS mutational status predict chemoresistance in advanced non-small cell
      lung cancer (NSCLC)?
AB  - BACKGROUND: Clinical implications of KRAS mutational status in advanced non-small
      cell lung cancer (NSCLC) remain unclear. To clarify this point, we
      retrospectively explored whether KRAS mutations could impact tumor response, and
      disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well
      as progression-free survival (PFS) or overall survival (OS). METHODS: Between
      June 2009 and June 2012, 340 patients with advanced (stage IIIB/IV) NSCLC were
      reviewed in a single institution (Institut Gustave Roussy). Two hundred and one
      patients had a biomolecular profile and received a platinum-based first-line CT.
      Patients with an unknown mutational status or with actionable alterations were
      excluded. We retained two groups: patients with KRAS mutated tumor (MUT) and
      patients with wild-type KRAS/EGFR (WT). Multivariate analyses with Cox model were
      used. Survival curves were calculated with Kaplan-Meier method. RESULTS: One
      hundred and eight patients were included in the analysis: 39 in the MUT group and
      69 in the WT group. Baseline radiological assessment demonstrated more brain
      (P=0.01) and liver (P=0.04) metastases in MUT patients. DCR was 76% for MUT vs.
      91% for WT group (P=0.03), regardless of the type of platinum-based CT (use of
      pemetrexed or not). Although no statistically significant differences were found,
      shorter PFS (4.9 vs. 6.0 months; P=0.79) and OS (10.3 vs. 13.2 months; P=0.40)
      were observed for patients with KRAS mutated tumors in univariate analysis.
      CONCLUSIONS: KRAS mutant tumors had a lower DCR after the first-line platinum
      based CT, but this difference did not translate in PFS or OS. The presence of
      KRAS mutations may confer a more aggressive disease, with greater baseline
      incidence of hepatic and cerebral metastases.

PMID- 24439570
TI  - Effect of total-body prehabilitation on postoperative outcomes: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To systematically review the evidence of pre-operative exercise, known
      as 'prehabilitation', on peri- and postoperative outcomes in adult surgical
      populations. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CENTRAL,
      Medline, EMBASE, CINAHL, PsycINFO and PEDro were searched from 1950 to 2011.
      METHODS: Two reviewers independently examined relevant, English-language articles
      that examined the effects of pre-operative total-body exercise with peri- and
      postoperative outcome analysis. Given the nascence of this field, controlled and
      uncontrolled trials were included. Risk of bias was assessed using the Cochrane
      Risk of Bias Assessment tool. Only data on length of stay were considered
      eligible for meta-analysis due to the heterogeneity of measures and methodologies
      for assessing other outcomes. RESULTS: In total, 4597 citations were identified
      by the search strategy, of which 21 studies were included. Trials were generally
      small (median=54 participants) and of moderate to poor methodological quality.
      Compared with standard care, the majority of studies found that total-body
      prehabilitation improved postoperative pain, length of stay and physical
      function, but it was not consistently effective in improving health-related
      quality of life or aerobic fitness in the studies that examined these outcomes.
      The meta-analysis indicated that prehabilitation reduced postoperative length of
      stay with a small to moderate effect size (Hedges' g=-0.39, P=0.033).
      Intervention-related adverse events were reported in two of 669 exercising
      participants. CONCLUSION: The literature provides early evidence that
      prehabilitation may reduce length of stay and possibly provide postoperative
      physical benefits. Cautious interpretation of these findings is warranted given
      modest methodological quality and significant risk of bias.

PMID- 24439571
TI  - Cryptic and biochemical responses of young cuttlefish Sepia officinalis exposed
      to environmentally relevant concentrations of fluoxetine.
AB  - Antidepressants released in the environment have the potential to generate neural
      disrupting effects in non-target organisms, yet their putative effects on
      behaviors have never been studied in cephalopod molluscs. This study assessed the
      impact of the antidepressant fluoxetine (FLX) on the efficiency of cryptic
      behaviors (body patterns on uniform, checkerboard and sandy substrates),
      locomotor activity, and brain chemistry in young cuttlefish exposed to
      environmental concentrations (1 and 100ngL(-1) of FLX) during the perinatal
      period. Behavioral responses of cuttlefish were monitored at hatching and two
      weeks later, and brain monoamine contents were quantified at one month of age.
      FLX significantly altered the camouflage efficiencies on uniform and sandy
      backgrounds only at the lowest concentration, but not at 100ngL(-1). Hatchlings
      exposed to 1ngL(-1) of FLX exhibited a duration exposure-dependent decrease in
      the uniform camouflage. They also showed a significant increase of the frequency
      of sand digging behaviors which might make them highly visible to predators in
      nature. When tested again two weeks later, cuttlefish seemed to have recovered
      and no more behavioral alterations were observed showing a transitory effect of
      the antidepressant. FLX did not affect the levels of serotonin, norepinephrine
      and their metabolites; however, it seemed to influence dopaminergic activity
      between the two FLX-exposed groups. The results show for the time that
      environmentally realistic concentrations of a single SSRI significantly impair
      the cryptic performances of newly hatched cuttlefish, and may ultimately reduce
      their chance for survival. 

PMID- 24439572
TI  - The right stuff.
AB  - We will discuss a new initiative of the American College of Surgeons and the
      American Pediatric Surgical Association to prospectively define optimal resource
      standards for children's surgical care. 

PMID- 24439573
TI  - Intestinal transplantation: an unexpected journey. Robert E. Gross Lecture.
AB  - The development of pediatric intestine transplantation has required continuous
      refinements in the management of intestinal failure, surgical technique, and
      perioperative care. The development of better immunosuppressive management
      (cyclosporine in 1978 and tacrolimus in 1989) and enhancements in our
      understanding of the relationship between recipient and host immune systems have
      resulted in better long-term survival. Paralleling this, advancements in the
      organ procurement techniques and organ preservation solutions have made possible
      the procurement and transplantation of various types of intestine containing
      grafts tailored to the needs of the various indications for which intestine
      transplantation is being performed. With improved outcomes, the indications for
      intestine transplantation have been better defined in the context of risk benefit
      for the most important complications of TPN, which include liver disease, life
      threatening infection, and loss of central venous access. The first survivors of
      transplantation would also go on to demonstrate the interaction (host-versus
      graft and graft-versus-host) between recipient and donor immunocytes (brought
      with the allograft), which under the cover of immunosuppression allows varying
      degrees of graft acceptance. The struggle to achieve better transplantation
      survival outcomes came about with the development of improved strategies to
      better manage intestinal failure. This has been accomplished largely through the
      establishment of centers that incorporate a multidisciplinary team approach to
      medical and surgical care. Intestine transplantation represents a lifesaving
      therapy for many patients with intestinal failure who have significant
      complications of their disease. It is hoped that with the minimization of
      immunosuppression strategies currently used, the long-term survival of these
      intestine organ transplant recipients will continue improving, together with
      their rehabilitation and quality-of-life. 

PMID- 24439574
TI  - Serendipity: translational research, high quality care, and the children's
      hospital. Jay and Margie Grosfeld Lecture.
AB  - The word "serendipity" was coined by Horace Walpole, Earl of Orford, in a letter
      he wrote in January 1754. He defined serendipity as the making of
      "....discoveries, by accidents and sagacity, of things which [you] were not in
      quest of....you must observe that no discovery of a thing you are looking for
      comes under this description." I would like to make the case that a children's
      hospital can be a superb setting in which to attempt this feat-to generate
      Serendipity. I would also like to convince you that this attribute is absolutely
      essential to providing the very best care for children. 

PMID- 24439575
TI  - 100 Years of inspiring quality at the ACS: how did we get here? Journal of
      Pediatric Surgery Lecture.
AB  - Throughout its 100-year history of working to ensure that surgical patients
      receive safe, high-quality, cost-effective care, the American College of Surgeons
      has adhered to four key principles: (1) Set the standards to identify and set the
      highest clinical standards based on the collection of outcomes data and other
      scientific evidence that can be customized to each patient's condition so that
      surgeons can offer the right care, at the right time, in the right setting. (2)
      Build the right infrastructure to provide the highest quality care with surgical
      facilities having in place appropriate and adequate staffing levels, a reasonable
      mix of specialists, and the right equipment. Checklists and health information
      technology, such as the electronic health record, are components of this
      infrastructure. (3) Collect robust data so that surgical decisions are based on
      clinical data drawn from medical charts that track patients after discharge from
      the hospital. Data should be risk-adjusted and collected in nationally
      benchmarked registries to allow institutions to compare their care with other
      providers. (4) Verify processes and infrastructure by having an external
      authority periodically affirm that the right systems are in place at health care
      institutions, that outcomes are being measured and benchmarked, and that
      hospitals and providers are proactively responding to these findings. 

PMID- 24439576
TI  - Validation of measures from a thoracoscopic esophageal atresia/tracheoesophageal
      fistula repair simulator.
AB  - PURPOSE: A validated high fidelity simulation model would provide a safe
      environment to teach thoracoscopic EA/TEF repair to novices. The study purpose
      was to evaluate validity evidence for performance measures on an EA/TEF
      simulator. METHODS: IRB-exempt data were collected from 12 self-reported "novice"
      and 8 "experienced" pediatric surgeons. Participants evaluated the EA/TEF repair
      simulator using survey ratings that were analyzed for test content validity
      evidence. Additionally, deidentified operative performances were videotaped and
      independently rated by two surgeons using the Objective Structured Assessment for
      Technical Skills (OSATS) instrument. Novice and experienced OSATS were compared
      with p<.05 significant. RESULTS: Participants had high overall simulator ratings.
      Internal structure was supported by high interitem consistency (alpha=.95 and
      .96) and interrater agreement (ICC) [.52, .84] for OSATS ratings. Experienced
      surgeons performed at a significantly higher level than novices for all five
      primary and two supplemental OSATS items (p<.05). CONCLUSION: Favorable
      participant ratings indicate the simulator is relevant to clinical practice and
      valuable as a learning tool. Further, performance ratings can discriminate
      experienced and novice performances of EA/TEF repair. These findings support the
      use of the simulator for performance assessment, representing the first validated
      measures from a simulator intended for pediatric surgical training.

PMID- 24439577
TI  - Maternal medical and behavioral risk factors for congenital diaphragmatic hernia.
AB  - PURPOSE: Maternal factors contributing to the etiology of congenital
      diaphragmatic hernia (CDH) remain unclear. We hypothesized that specific maternal
      medical conditions (pregestational diabetes, hypertension), and behaviors
      (alcohol, tobacco) would be associated with CDH. METHODS: We conducted a
      population-based case-control study using Washington State birth certificates
      linked to hospital discharge records (1987-2009). We identified all infants with
      CDH (n=492). Controls were randomly selected among non-CDH infants. Maternal data
      were extracted from the birth record. Logistic regression was used to adjust for
      covariates. RESULTS: Cases and controls were generally similar regarding
      demographics, although CDH infants were more likely to be male than controls
      (58.5% vs. 52.5%). Isolated and complex (multiple-anomaly) CDH had similar
      characteristics. Each of the exposures of interest was more common among case
      mothers than among control mothers. In univariate analysis, alcohol use,
      hypertension, and pregestational diabetes were each significantly associated with
      the outcome. After multivariate adjustment, only alcohol use (OR=3.65, p=0.01)
      and pregestational diabetes (OR=12.53, p=0.003) maintained significance. Results
      were similar for both isolated and complex CDH. CONCLUSIONS: Maternal
      pregestational diabetes and alcohol use are significantly associated with
      occurrence of CDH in infants. These are important modifiable risk factors to
      consider with regard to efforts seeking to impact the incidence of CDH.

PMID- 24439579
TI  - Increased risk of cardiovascular perforation during ECMO with a bicaval, wire
      reinforced cannula.
AB  - PURPOSE: Cardiac or major vascular perforation is a rare but serious risk of
      ECMO. We sought to determine if perforation rates are related to cannula design.
      METHODS: We utilized three methods to evaluate perforation on ECMO. 1. The ELSO
      registry was queried to establish the historical rate of hemorrhagic pericardial
      tamponade. 2. ELSO centers were surveyed regarding cannula related perforation
      events and brands of cannulas used over a four year time period (January 2008
      March 2012). 3. The FDA's MAUDE database was reviewed looking for adverse events
      related to ECMO cannulas. RESULTS: The historical rate of hemorrhagic pericardial
      tamponade in the ELSO registry was 0.53% (~1985-2010, ELSO registry). In the
      survey there were eleven reports of cannula-related perforation, 0.74% (11/1482 p
      value=0.29) at 7 different ELSO centers with 23 ELSO centers responding (17%
      response rate). The incidence of perforation was much higher for the wire
      reinforced bicaval design 3.6% (10/279) as compared to catheters designed for the
      atrial position, 0.1% (1/1203, p-value<0.0001). Review of the FDA's MAUDE
      database revealed 19 adverse events related to the bicaval cannula design, 16 of
      which were hemorrhagic pericardial effusions or tamponade. CONCLUSION: These
      findings suggest a relatively high rate of cardiac perforation associated with
      the dual lumen bicaval cannula. This may be related to inherent differences in
      cannula design or the IVC positioning required by the design.

PMID- 24439578
TI  - Antenatal maternally-administered phosphodiesterase type 5 inhibitors normalize
      eNOS expression in the fetal lamb model of congenital diaphragmatic hernia.
AB  - PURPOSE: Pulmonary hypertension (pHTN), a main determinant of survival in
      congenital diaphragmatic hernia (CDH), results from in utero vascular remodeling.
      Phosphodiesterase type 5 (PDE5) inhibitors have never been used antenatally to
      treat pHTN. The purpose of this study is to determine if antenatal PDE5
      inhibitors can prevent pHTN in the fetal lamb model of CDH. METHODS: CDH was
      created in pregnant ewes. Postoperatively, pregnant ewes received oral placebo or
      tadalafil, a PDE5 inhibitor, until delivery. Near term gestation, lambs underwent
      resuscitations, and lung tissue was snap frozen for protein analysis. RESULTS:
      Mean cGMP levels were 0.53+/-0.11 in placebo-treated fetal lambs and 1.73+/-0.21
      in tadalafil-treated fetal lambs (p=0.002). Normalized expression of eNOS was
      82%+/-12% in Normal-Placebo, 61%+/-5% in CDH-Placebo, 116%+/-6% in Normal
      Tadalafil, and 86%+/-8% in CDH-Tadalafil lambs. Normalized expression of beta-sGC
      was 105%+/-15% in Normal-Placebo, 82%+/-3% in CDH-Placebo, 158%+/-16% in Normal
      Tadalafil, and 86%+/-8% in CDH-Tadalafil lambs. Endothelial NOS and beta-sGC were
      significantly decreased in CDH (p=0.0007 and 0.01 for eNOS and beta-sGC,
      respectively), and tadalafil significantly increased eNOS expression (p=0.0002).
      CONCLUSIONS: PDE5 inhibitors can cross the placental barrier. beta-sGC and eNOS
      are downregulated in fetal lambs with CDH. Antenatal PDE5 inhibitors normalize
      eNOS and may prevent in utero vascular remodeling in CDH.

PMID- 24439580
TI  - Chest tube placement in children during extracorporeal membrane oxygenation
      (ECMO).
AB  - BACKGROUND: Pleural collections of air and fluid are frequent in infants and
      children treated with extracorporeal membrane oxygenation (ECMO). In this
      anticoagulated population, chest tube placement is potentially hazardous, and
      catastrophic hemorrhage has been reported. We sought to define the risks
      associated with chest tube placement in a large population of children managed
      with ECMO. METHODS: The records of 189 consecutive children managed with ECMO at
      two children's hospitals were reviewed. Demographics, indications for ECMO, and
      ECMO courses were reviewed. In particular, the occurrence of pleural collections
      and the frequency and technique of chest tube placement were evaluated. The
      incidence of complications and mortality were determined. RESULTS: The median age
      of the subjects was 2days. The overall mortality was 26.5%. A pneumothorax was
      found in 19 (10.1%), a pleural effusion in 26 (13.8%), and a hemothorax in 2
      (1.0%). A chest tube was placed in 27 (19 by a needle-guide wire technique and 8
      by cut-down). Major bleeding complications occurred in 6 subjects (22%).
      CONCLUSIONS: There was a significant incidence of major bleeding complications
      and death in subjects in whom chest tubes were placed. The placement of a chest
      tube during ECMO should be done only if it is likely to improve pump flow or
      promote weaning of support.

PMID- 24439581
TI  - Operative management of acquired Jeune's syndrome.
AB  - BACKGROUND: Acquired Jeune's syndrome is a severe iatrogenic deformity of the
      thoracic wall following a premature and aggressive open pectus excavatum repair.
      We report herein our technique and experience with this rare condition. METHODS:
      From 1996 to 2011, nineteen patients with acquired Jeune's syndrome were
      retrospectively identified in a tertiary referral center. The technique used to
      expand and reconstruct the thoracic wall consisted of 1) release of the sternum
      from fibrous scar tissue, 2) multiple osteotomies along the lateral aspect of the
      ribs with anterior advancement of costal-cartilages to protect the heart, 3)
      stabilization of the thorax by placing a curved bar for retrosternal support and,
      4) restoration of the sterno-costal junction by wiring the lower cartilages to
      the edge of the sternum. RESULTS: Major complications observed in this series
      were: bar displacement (seven cases), postoperative death from cardiac arrest
      following bronchoscopy (one case), late cardiac tamponade from migration of wire
      suture fragment (one case), and need for multiple reoperations (one case). Long
      term cosmetic results and improvement in daily quality of life were reported as
      positive in the majority of cases. CONCLUSIONS: Anterior chest wall
      reconstruction successfully treated our series of patients with acquired Jeune's
      syndrome. This multifaceted technique is an effective procedure that allows
      expansion of the thoracic cavity and improvement of aerobic activity.

PMID- 24439582
TI  - Pressure induced lung injury in a novel in vitro model of the alveolar interface:
      protective effect of dexamethasone.
AB  - PURPOSE: The lungs of infants born with congenital diaphragmatic hernia suffer
      from immaturity as well as the short and long term consequences of ventilator
      induced lung injury, including chronic lung disease. Antenatal and postnatal
      steroids are among current strategies promoted to treat premature lungs and limit
      long term morbidity. Although studied in whole-animal models, insight into
      ventilator-induced injury at the alveolar-capillary interface as well as the
      benefits of steroids, remains limited. The present study utilizes a multi-fluidic
      in vitro model of the alveolar-interface to analyze membrane disruption from
      compressive aerodynamic forces in dexamethasone-treated cultures. METHODS: Human
      alveolar epithelial cell lines, H441 and A549, were cultured in a custom-built
      chamber under constant aerodynamic shear followed by introduction of pressure
      stimuli with and without dexamethasone (0.1MUM). On-chip bioelectrical
      measurements were noted to track changes to the cellular surface and live-dead
      assay to ascertain cellular viability. RESULTS: Pressure-exposed alveolar
      cultures demonstrated a significant drop in TEER that was less prominent with an
      underlying extracellular-matrix coating. Addition of dexamethasone resulted in
      increased alveolar layer integrity demonstrated by higher TEER values.
      Furthermore, dexamethasone-treated cells exhibited faster recovery, and the
      effects of pressure appeared to be mitigated in both cell types. CONCLUSION:
      Using a novel in vitro model of the alveolus, we demonstrate a dose-response
      relationship between pressure application and loss of alveolar layer integrity.
      This effect appears to be alleviated by dexamethasone and matrix sub-coating.

PMID- 24439583
TI  - Surgical approaches to aortopexy for severe tracheomalacia.
AB  - PURPOSE: The purpose of this study was to determine the outcomes among three
      different surgical approaches for performing an aortopexy to treat severe
      tracheomalacia (STM). METHODS: A retrospective review was performed for all
      patients who underwent an aortopexy by pediatric surgeons at a single institution
      during 1997-2012. Data collected included details of the operative approaches and
      clinical results. The data were analyzed using Chi-square and Fisher exact test.
      RESULTS: Forty-one patients underwent an aortopexy. The operation was chosen by
      the surgeon and not randomized. Exposure was by partial sternotomy (PS) (20),
      open thoracotomy (12), or thoracoscopic approach (7). Only the PS approach was
      done by a single team. All groups showed improvement in work of breathing,
      prevention of severe respiratory distress, and acute life threatening events.
      These effects were more dramatic for the PS group, especially regarding oxygen
      and/or ventilator dependence and the ability to undergo tracheostomy
      decannulation. Among the sixteen patients with failure-to-thrive before
      successful aortopexy by any technique, ten demonstrated significant improvement
      in their growth (p=0.025). The recurrence rate for the thoracoscopic approach was
      38%, and there were no recurrences in the partial sternotomy and the thoracotomy
      groups, 38% vs 0% vs 0%, p=0.005. Simultaneous bronchoscopy was utilized more
      commonly in the PS group compared to the thoracotomy and thoracoscopic group, 95%
      vs 62% vs 38%. CONCLUSIONS: In this series, the partial sternotomy technique had
      the most reliable resolution of symptoms and no recurrence requiring reoperation.
      The PS approach to STM has the technical advantages of an improved exposure with
      equal access to the vessels over the right and left mainstem bronchi, as well as
      the trachea and a more specific elevation of the arteries, including suspension
      of the pulmonary arteries and trachea itself when desirable. Simultaneous
      bronchoscopy during aortopexy and an experienced team also likely contribute to
      improved outcomes. The variations in populations, follow-up, and use of
      continuous intraoperative bronchoscopy, however, make firm conclusions difficult.

PMID- 24439584
TI  - Evaluation of laparoscopic management of recurrent gastroesophageal reflux
      disease and hiatal hernia: long term results and evaluation of changing trends.
AB  - INTRODUCTION: Recurrent gastro-esophageal reflux disease (GERD) following
      fundoplication remains a common problem. This study evaluates a long-term
      experience with laparoscopic management of these cases. METHODS: From January
      1994 to December 2012, 252 patients with recurrent GERD underwent a laparoscopic
      redo Nissen (LRN) fundoplication with average age of 6.8years. Eighty-four had
      previous open fundoplications and 144 previous LNRs. Thirty-two had more than one
      previous fundoplication. RESULTS: All procedures were completed laparoscopically.
      The average operative time was 82min. The intra-operative complication rate was
      5.1%, the most common being a gastrostomy during the mobilization. The average
      time to full feeds was 1.4days, and the average hospital stay was 1.6days. The
      post-operative complication rate was 3.6%. The wrap failure rate was 6.2%. The
      most common cause of wrap failure was H/H, with increasing incidence of slipped
      wrap during the second half. The highest recurrence rate was in patients
      receiving their LNR before 4months of age. CONCLUSIONS: Redo Laparoscopic Nissen
      fundoplication is safe and effective, with the same benefits as a primary
      laparoscopic Nissen, with low morbidity and quick recovery. A change in the
      etiology of recurrence suggests that there is a failure to adequately identify
      and mobilize the GE junction in laparoscopic cases.

PMID- 24439585
TI  - The problematic Soave cuff in Hirschsprung disease: manifestations and treatment.
AB  - PURPOSE: Following a Soave pull-through for Hirschsprung disease (HD), some
      children struggle with obstructive symptoms. We hypothesized that these symptoms
      could result from a functional obstruction of the pull through caused by the
      Soave cuff, and that cuff resection might improve bowel emptying. METHODS: We
      reviewed patients referred to our center from 2008 to 2012 with obstructive
      problems following a Soave pull-through for HD (CCHMC IRB # 2011-2019). Only
      patients with an obstructing Soave cuff were analyzed. Patients with other
      reasons for obstruction (anastomotic stricture, transition zone, aganglionic
      segment) were excluded. RESULTS: Thirty-six patients underwent reoperation at our
      center for obstructive symptoms after an initial Soave pull-through. Seventeen of
      these patients had a Soave cuff only as the potential source of obstruction. Pre
      operative symptoms included enterocolitis (10), constipation (6), and failure to
      thrive (1). Nine patients (53%) required irrigations to manage distension or
      enterocolitis pre-operatively. 14/17 patients (82%) had a palpable cuff on rectal
      exam. Eight patients (47%) had radiographic evidence of a cuff demonstrated by
      distal narrowing (4) or a prominent presacral space (4). Four children (23%)
      underwent excision of the cuff only. Thirteen (76%) had removal of the cuff and
      proximally dilated colon [(average length 7.2cm) (12 performed transanally, and
      five needed laparotomy as well.)] Post-operatively, episodes of enterocolitis
      were reduced to zero, and need for irrigation to treat distension was reduced by
      50%. Nine patients have voluntary bowel movements, and five are clean on enemas.
      3/6 patients with pre-operative constipation or impaction now empty without
      enemas. (Follow up 1-17months, mean 7months.) CONCLUSIONS: Recurrent
      enterocolitis, constipation, or failure to thrive can indicate a functional
      obstruction due to a Soave cuff when no other pathologic cause exists. Physical
      exam or contrast enema can identify a problematic cuff. Reoperation with cuff
      resection can dramatically improve bowel emptying.

PMID- 24439586
TI  - The natural history of familial adenomatous polyposis syndrome: a 24 year review
      of a single center experience in screening, diagnosis, and outcomes.
AB  - PURPOSE: Understanding the natural history of Familial Adenomatous Polyposis
      (FAP) will guide screening and aid clinical management. METHODS: Patients with
      FAP, age <=20years presenting between 1987 and 2011, were reviewed for
      presentation, diagnosis, extraintestinal manifestations, polyp burden, family
      history, histology, gene mutation, surgical intervention, and outcome. RESULTS:
      One hundred sixty-three FAP patients were identified. Diagnosis was made by
      colonoscopy (69%) or genetic screening (25%) at mean age of 12.5years. Most
      children (58%) were asymptomatic and diagnosed via screening due to family
      history. Rectal bleeding was the most common (37%) symptom prompting evaluation.
      Colon polyps appeared by mean age of 13.4years with >50 polyps at the time of
      diagnosis in 60%. Cancer was found in 1 colonoscopy biopsy and 5 colectomy
      specimens. Family history of FAP was known in 85%. 53% had genetic testing, which
      confirmed APC mutation in 88%. Extraintestinal manifestations included congenital
      hypertrophy of the retinal pigment epithelium (11.3%), desmoids (10.6%), osteomas
      (6.7%), epidermal cysts (5.5%), extranumerary teeth (3.7%), papillary thyroid
      cancer (3.1%), and hepatoblastoma (2.5%). Six patients died secondary to FAP.
      CONCLUSIONS: Clinical presentation and manifestations in pediatric FAP are
      variable. We suggest an individualized patient-oriented screening algorithm that
      allows for earlier screening and appropriate management.

PMID- 24439587
TI  - Loop versus divided colostomy for the management of anorectal malformations.
AB  - PURPOSE: The purpose of this study was to compare the clinical outcomes of loop
      and divided colostomies in patients with anorectal malformations (ARM). METHODS:
      We performed a retrospective cohort study reviewing the medical records of all
      patients with ARM managed with diverting colostomies between 2000 and 2010 at our
      institution. Independent variables and outcomes of stoma complications were
      analyzed by parametric measures and logistic regression. RESULTS: One hundred
      forty-four patients managed with a colostomy for ARM were evaluated (37.5%
      females, 50.7% loop, 49.3% divided). The incidence of patients with loop and
      divided colostomies who developed stoma-related complications was 31.5 and 15.5%,
      respectively (p=0.031). The incidence of prolapse was 17.8 and 2.8%, respectively
      (p=0.005). Multivariable-logistic regression controlling for other significant
      independent variables found loop colostomies to be positively associated with the
      development of a stoma complication (OR 3.13, 95%CI (1.09, 8.96), p=0.033). When
      individual complications were evaluated, it was only stoma prolapse that was more
      likely in patients with loop colostomies (OR 8.75, 95%CI (1.74, 44.16), p=0.009).
      CONCLUSION: Because of the higher incidence of prolapse, loop colostomies were
      found to be associated with a higher total incidence of complications than
      divided stomas. The development of other complications, including urinary tract
      infections (UTIs) and megarectum, were independent of the type of colostomy
      performed.

PMID- 24439588
TI  - Vesicoureteral reflux and febrile urinary tract infections in anorectal
      malformations: a retrospective review.
AB  - BACKGROUND: Multiple studies document a correlation between anorectal
      malformations (ARMs) and vesicoureteral reflux (VUR), development of urinary
      tract infections (UTIs), and subsequent renal disease. We aimed to determine
      which patient characteristics are associated with VUR and UTI in this population.
      METHODS: A retrospective review of ARM patients at a free-standing children's
      hospital from January 1996 to December 2011 was performed. Logistic regression
      was used to investigate the associations between VUR and UTI and ARM
      classification and co-morbid diagnoses. RESULTS: Of 190 patients, 41 (31%)
      received a diagnosis of VUR. Thirty-one of the 190 patients had at least one
      febrile UTI (16%). Of these, only 16 (51%) had a diagnosis of VUR. On
      multivariable logistic regression, the only patient variable associated with VUR
      was having an ectopic kidney (p=0.026). Similarly, the presence of GU
      malformations was the closest variable associated with developing a UTI
      (p=0.073). CONCLUSIONS: In ARM patients, VUR as well as UTIs are associated with
      the presence of GU malformations. Thus, voiding cystourethrogram (VCUG) testing
      should be pursued when there are other caudal and GU abnormalities, regardless of
      fistula location. Antibiotic prophylaxis for UTI should be considered in children
      with ARM and any GU malformation, not only VUR.

PMID- 24439589
TI  - Complete VACTERL evaluation is needed in newborns with rectoperineal fistula.
AB  - PURPOSE: Given that a rectoperineal fistula is developmentally the most mature
      lesion in the spectrum of anorectal malformations, it is not clear whether it
      merits a complete VACTERL evaluation. We sought to determine if the same
      evaluation is required to rule out associated anomalies in newborns with
      rectoperineal fistula as those with more complex anorectal malformations.
      METHODS: We performed a retrospective review of the pediatric colorectal center
      database at our tertiary care children's hospital from 2000 to 2012. Patients
      with anorectal malformations were categorized as rectoperineal fistula or "other"
      using the Krickenbeck classification. Records were reviewed to identify
      associated anomalies. RESULTS: 308 patients (156 males) were treated at our
      institution during the time period (rectoperineal fistula=102). Thirty-five (34%)
      patients with a perineal fistula had at least one associated anomaly. The most
      common anomalies were cardiac lesions (29% excluding PFO and PDA), genitourinary
      (20.6%), and malformations of the spine (15.7%). The overall occurrence of
      anomalies was lower than the "other" group. CONCLUSION: Our review demonstrates
      that newborns with a rectoperineal fistula frequently have associated anomalies
      and should undergo an evaluation similar to more complex lesions. These findings
      illustrate the importance of a structured approach to the evaluation of even the
      most straightforward lesions.

PMID- 24439590
TI  - Fast-track management is safe and effective after bowel resection in children
      with Crohn's disease.
AB  - BACKGROUND: "Fast-track" management (FT) challenges traditional postoperative
      tenets in order to minimize discomfort and optimize inpatient care. We examined
      the outcomes of consecutively performed laparoscopic-assisted ileocecectomy for
      Crohn's disease (CD), with particular focus on FT's effects in patients with
      underlying bowel inflammation. METHODS: We retrospectively reviewed all patients
      undergoing isolated laparoscopic-assisted ileocecectomy for CD at our institution
      between 12/2000 and 12/2010, excluding patients with multiple areas of surgical
      CD, bladder involvement, or age >18years. RESULTS: Seventy-one patients aged 8
      18years underwent isolated laparoscopic-assisted ileocecectomy for CD, of which
      45 met FT criteria. Individual practice patterns primarily determined which
      patients were FT-managed. FT management led to decreased length of stay (LOS),
      time to first stool, time to full diet, and intravenous narcotic use. No
      significant difference in complications or disease progression was observed
      between the two groups during 2-year follow up. CONCLUSIONS: Our results suggest
      that FT is safe and effective in patients with CD. In a chronically ill
      population, counseling patients and families to expect early discharge is
      critical to the success of this strategy. Despite CD-related GI pathology, FT
      patients realized benefits in terms of LOS, time to bowel function, and narcotic
      use without any increase in complications.

PMID- 24439591
TI  - First STEPs: serial transverse enteroplasty as a primary procedure in neonates
      with congenital short bowel.
AB  - BACKGROUND: Since its introduction as an alternative intestinal lengthening
      technique, serial transverse enteroplasty (STEP) has been increasingly used as
      the surgical treatment of choice for patients with refractory short bowel
      syndrome (SBS). While primary STEP for the treatment of congenital conditions was
      proposed in the original description of the procedure, emphasis was placed on a
      delayed or staged approach to these patients. To date, a comprehensive review of
      the outcomes from this sub-population has not been reported by the International
      STEP Data Registry. METHODS: A retrospective review of the International STEP
      Data Registry was performed to identify all patients who underwent STEP as a
      primary operative procedure for the treatment of congenital SBS. Changes in pre-
      and post-STEP values were assessed using paired t-tests with significance set at
      p<0.05. Data are presented as mean +/- standard deviation. RESULTS: Fifteen
      patients underwent primary STEP for congenital SBS between September 1, 2004, and
      April 10, 2012. Thirteen patients had follow-up information available. Causes of
      congenital SBS included closing gastroschisis, small bowel atresia, and midgut
      volvulus. Twelve patients had pre- and post-STEP bowel measurements taken.
      Average pre- and post-STEP bowel lengths were 32 +/- 16 cm and 47 +/- 22 cm,
      respectively. Intestinal length was increased by a mean of 15 +/- 12 cm for a
      relative small bowel length increase of 50.4 +/- 27.3% (p<0.001). Only one
      patient required an ostomy at the time of primary STEP. A second patient required
      a temporary ostomy at 3months of age that was later closed. There was one death
      from intestinal failure associated liver disease (IFALD). Another patient
      experienced IFALD progression and required liver and intestinal transplantation.
      The most commonly reported complication following primary STEP was obstruction or
      bowel re-dilatation requiring additional operative interventions. Nine patients
      underwent second STEP procedures under these circumstances. Eight patients remain
      dependent on parenteral nutrition, while three patients achieved enteral
      autonomy. CONCLUSIONS: Primary STEP is a feasible and safe surgical option for
      the treatment of congenital conditions resulting in SBS. Primary STEP establishes
      early bowel continuity, creates intestinal length from congenitally dilated
      bowel, and appears to obviate the need for interval stomas and their associated
      loss of bowel length in neonates with congenital SBS. However, with recent
      changes in SBS management emphasizing intestinal rehabilitation, additional
      studies are needed to assess the long-term impact on intestinal adaptation of
      STEP performed in the neonatal period prior to adoption of this technique.

PMID- 24439592
TI  - A novel biodegradable device for intestinal lengthening.
AB  - PURPOSE: Previous studies demonstrated successful mechanical lengthening of rat
      jejunum using an encapsulated Nitinol spring device over a stabilizing guidewire.
      We sought to improve the applicability of intestinal lengthening by creating a
      biodegradable device. METHODS: Using properties of the Nitinol spring device,
      polycaprolactone (PCL) springs with similar outer diameter and spring constant
      were created. After in vitro testing in dry and hydrated environments, they were
      used to lengthen 1-cm isolated segments of rat jejunum in vivo. Retrieved
      segments were analyzed histologically. RESULTS: Optimal PCL spring devices had an
      average spring constant 1.8 +/- 0.4 N/m, pitch 1.55 +/- 0.85 mm, and band width
      0.825 +/- 0.016 mm. In vitro testing demonstrated stable spring constants.
      Jejunal segments were lengthened from 1.0 cm to 2.7 +/- 0.4 cm without needing a
      stabilizing guidewire. Histology demonstrated increased smooth muscle thickness
      and fewer ganglia compared to controls. Lengthened jejunum was successfully
      restored into intestinal continuity and demonstrated peristalsis under
      fluoroscopy. CONCLUSIONS: A novel biodegradable spring device was successfully
      created and used to mechanically lengthen intestinal segments. Use of a
      biodegradable device may obviate the need for retrieval after lengthening. This
      improves device applicability and may be useful for the treatment of short bowel
      syndrome.

PMID- 24439593
TI  - Intestinal muscularis propria increases in thickness with corrected gestational
      age and is focally attenuated in patients with isolated intestinal perforations.
AB  - PURPOSE: Intestinal perforations are common in premature infants, leading to a
      diagnostic dilemma between necrotizing enterocolitis and isolated intestinal
      perforation (IIP). IIP is thought to result from a congenital or acquired absence
      of the muscularis propria. However, developmental events leading to IIP are not
      well understood. This study examines the relationship between corrected
      gestational age (CGA) and intestinal muscle development in controls and patients
      with IIP. METHODS: Specimens from stillbirths and infants undergoing intestinal
      surgery from 8 to 48weeks' CGA were collected from 2005 to 2012. Twelve patients
      with IIP were identified. Control specimens were collected during 25 fetal
      autopsies and 39 bowel resections. In each case, three sections of intestine were
      examined histologically for muscularis mucosa, circular and longitudinal muscle
      thickness. Comparisons of control and perforated specimens were performed via
      linear regression and ANOVA. RESULTS: Controls and adjacent normal segments in
      IIP showed a linear relationship between thickness of circular and longitudinal
      muscles with CGA. Circular and longitudinal muscles were thinner in perforated
      segments than in adjacent normals and CGA-matched controls (p<0.05). CONCLUSION:
      Intestinal muscularis propria increases in thickness with CGA. Muscle thickness
      is focally attenuated in patients with isolated intestinal perforations, while
      the remaining intestine is normal, suggesting that primary repair is an
      appropriate treatment.

PMID- 24439594
TI  - Patient and parental scar assessment after single incision versus standard 3-port
      laparoscopic appendectomy: long-term follow-up from a prospective randomized
      trial.
AB  - BACKGROUND: Single site laparoscopy for appendectomy is a technique with several
      case series suggesting a cosmetic advantage, but without prospective comparative
      data. We conducted a prospective, randomized trial comparing single site
      laparoscopic appendectomy to the standard 3-port approach, including scar
      assessment at early and long-term follow-up. METHODS: Enrolled patients over
      12years old and parents of patients less than 12years old were asked to complete
      the validated Patient Scar Assessment Questionnaire (PSAQ) at early follow-up
      around 6weeks and by phone after 18months. The PSAQ consists of 4 scored
      subscales: Appearance, Consciousness, Appearance Satisfaction, and Symptom
      Satisfaction. Each subscale has a set of questions with a 4-point categorical
      response (1=most favorable, 4=least favorable). The sum of the scores quantifies
      each subscale. RESULTS: Early questionnaires were obtained from 98 3-port and 100
      single-site patients with the single-site approach producing superior overall
      scar assessment (P=0.003). By telephone follow-up, questionnaires were completed
      by 49 3-port and 56 single-site patients at a median of 25 (18-32) months. In
      this longer-term follow-up, overall scar assessment was not significantly
      different between groups (P=0.06). CONCLUSION: Patients or parents express
      superior scar assessment with the single site approach at early follow-up, but
      this difference disappears in the long-term.

PMID- 24439595
TI  - Shifts towards pediatric specialists in the treatment of appendicitis and pyloric
      stenosis: trends and outcomes.
AB  - BACKGROUND: Little data exists on temporal changes in the care of children with
      common surgical conditions. We hypothesized that an increasing proportion of
      procedures are performed at pediatric hospitals over time, and that outcomes are
      superior at these centers. METHODS: We conducted a retrospective cohort study
      using Washington State discharge records for children 0-17years old undergoing
      appendectomy (n=39,472) or pyloromyotomy (n=3,500). Pediatric hospitals were
      defined as centers with full-time pediatric surgeons. Outcomes were examined for
      two time periods (1987-2000, 2001-2009). RESULTS: From 1987 to 2009, the
      proportion of procedures performed at pediatric hospitals steadily increased. The
      percentage for appendectomies increased from 17% to 32%, and that for
      pyloromyotomies increased from 57% to 99%. For pyloromyotomy, care at a pediatric
      hospital was associated with decreased risk of postoperative complications
      (OR=0.36, p<0.001) for both time periods. Appendectomy outcomes did not differ
      significantly in the early time period, but in the later time period specialist
      care was associated with lower risk of complications in children <5years
      (OR=0.54, p=0.03). CONCLUSION: There has been a shift towards pediatric hospitals
      for certain procedures, with a widening disparity in outcomes for younger
      children. These results suggest that procedures in younger patients may best be
      performed by providers familiar with these patient populations.

PMID- 24439596
TI  - Protocol versus ad libitum feeds after laparoscopic pyloromyotomy: a prospective
      randomized trial.
AB  - BACKGROUND: We conducted a prospective, randomized trial comparing protocol to ad
      libitum (ad lib) feeding after laparoscopic pyloromyotomy. METHODS: Infants
      undergoing laparoscopic pyloromyotomy were randomized to protocol versus ad lib
      feeding strategies. The protocol started with Pedialyte(r) two hours post
      operative. This was repeated by another round of Pedialyte(r), then two rounds of
      half-strength formula or breast milk, followed by two rounds of full strength
      formula or breast milk, followed by the home feeding regimen, at which time the
      patient was discharged if feeding well. The ad lib group was allowed formula or
      breast milk two hours after the operation and considered for discharge after
      tolerating three consecutive feeds. The primary outcome variable was the length
      of postoperative hospitalization. RESULTS: One hundred fifty infants were
      enrolled between January 2010 and December 2011. There were no differences in
      patient characteristics at presentation. While the ad lib group reached goal
      feeds sooner than the protocol group, this did not translate into a difference in
      duration of postoperative hospitalization. There were more patients with emesis
      in the ad lib group after goal feeding was reached, but no difference in
      readmissions. CONCLUSION: Ad lib feeding allows patients to reach goal feeds more
      rapidly than protocol feeding following laparoscopic pyloromyotomy. However, this
      goal is usually reached beyond discharge hours, resulting in a similar duration
      of hospitalization.

PMID- 24439597
TI  - In utero repair of myelomeningocele with autologous amniotic membrane in the
      fetal lamb model.
AB  - BACKGROUND: Despite advances in prenatal repair, myelomeningocele (MMC) still
      produces devastating neurologic deficits. The amniotic membranes (AM) are a
      biologically active tissue that has been used anecdotally for human fetal MMC
      repair. This study evaluated the use of autologous AM compared to skin closure in
      an established fetal MMC model. METHODS: Seven fetal lambs underwent surgical
      creation of MMC at gestational age of 75days followed by in utero repair at
      gestational age of 100days. Lambs were repaired with an autologous AM patch
      followed by skin closure (n=4) or skin closure alone (n=3). Gross necropsy and
      histopathology of the spinal cords were performed at term to assess neuronal
      preservation at the lesion. RESULTS: An increase in preserved motor neurons and a
      larger area of spinal cord tissue were seen in AM-repaired lambs, as was
      decreased wound healing of the overlying skin. Loss of nearly all spinal cord
      tissue with limited motor neuron preservation was seen in skin only-repaired
      lambs. CONCLUSIONS: AM-repaired lambs showed increased protection of spinal cord
      tissue compared to skin only-repaired lambs, but the overlying skin failed to
      close in AM-repaired lambs. These results suggest a potential role for AM in
      fetal MMC repair that warrants further study.

PMID- 24439598
TI  - Urologic and anorectal complications of sacrococcygeal teratomas: prenatal and
      postnatal predictors.
AB  - PURPOSE: Anorectal and urologic sequelae are observed in long-term survivors of
      sacrococcygeal teratoma (SCT). In this study we evaluate the incidence and
      predictors of anorectal and urologic complications in SCT. METHODS: A
      retrospective review was performed for all SCT patients who underwent resection
      at a single institution between 2000 and 2012. Enrollment criteria included a
      minimum of 12months follow-up. Categorical variables were analyzed by Fisher's
      exact test and continuous variables by Mann Whitney test (p<0.05). RESULTS: Forty
      five patients were studied. Anorectal complications occurred in 29%, including
      severe chronic constipation (n=13) and fecal incontinence (n=4). Urologic
      complications occurred in 33%, including neurogenic bladder (n=12),
      vesicoureteral reflux (n=5), and urinary incontinence (n=7). Prenatal imaging by
      fetal MRI demonstrated mass effect with obstruction of the bowel (n=4) or bladder
      and collecting system (n=7) in a subset of patients with postnatal complications
      (anorectal 4/4, PPV 100%; urologic 6/7, PPV 86%). Postnatal complications were
      associated with obstructive findings on prenatal imaging, prenatal therapeutic
      interventions, Altman classification, perineal reconstruction, and tumor
      recurrence. No anorectal or urologic complications occurred in patients with
      Altman type I tumors. CONCLUSIONS: Urologic and anorectal complications are
      common in patients with SCT. Higher Altman classification and prenatal imaging
      suggestive of intestinal or urologic obstruction should prompt focused prenatal
      counseling and postnatal screening for anorectal and urologic dysfunction.

PMID- 24439599
TI  - Predictors of ovarian malignancy in children: overcoming clinical barriers of
      ovarian preservation.
AB  - BACKGROUND/PURPOSE: Ovarian preservation is desirable in girls with benign
      ovarian masses. We aimed to 1) identify clinical predictors of malignant ovarian
      masses, 2) investigate how often ovarian tissue is present to preserve in benign
      masses, and 3) identify factors associated with successful ovarian preservation.
      METHODS: Retrospective analysis (1997-2012) of girls age 1-18years with an
      ovarian mass managed operatively. Data on presenting symptoms, imaging,
      biochemical markers, treatment, outcome, and pathology were extracted. RESULTS:
      We identified 150 patients. Large mass size, solid components, and elevated tumor
      markers (AFP, betaHCG, and/or LDH) were significantly predictive of malignancy.
      All masses <10cm, predominantly cystic, and with negative tumor markers were
      benign. Masses with all three of these characteristics would decrease a 20%
      malignancy pretest probability to a posttest probability of 0.25%. Benign masses
      managed by oophorectomy contained normal ovarian tissue in 76% of the specimens.
      For benign masses, successful ovarian preservation was significantly associated
      with size <10cm, predominantly cystic, laparoscopy, and absence of torsion or
      calcifications. CONCLUSION: Ovarian masses that are <10cm, primarily cystic, and
      have negative tumor markers are most likely benign. Viable ovarian tissue is
      frequently present in benign masses, so significant efforts should be made for
      ovarian preservation.

PMID- 24439600
TI  - Repeat nephron-sparing surgery for children with bilateral Wilms tumor.
AB  - BACKGROUND: Renal insufficiency is a significant complication of Wilms tumor
      treatment in the 5% with bilateral disease. Nephron-sparing surgery (NSS) is
      recommended after neoadjuvant chemotherapy initially. However, the role of NSS in
      recurrent disease is unknown. We reviewed our experience to assess the
      feasibility and oncologic and functional outcomes of repeat NSS for children with
      recurrent disease. METHODS: A retrospective review was performed of all children
      treated at our institution for bilateral, favorable histology (FH) Wilms tumor.
      Patients undergoing repeat NSS for locally recurrent disease were identified. The
      outcomes evaluated included tumor recurrence, renal function, and patient
      survival. RESULTS: Since 2001, 36 children with bilateral FH Wilms tumor have
      been treated at our institution. Eight patients (22%) underwent repeat NSS for
      locally recurrent disease. Two patients had a second local recurrence and
      underwent a third NSS. Six patients are alive without disease (75%) with an
      average follow-up of 4.5years. Two patients have died, each with blastemal
      predominant histology at repeat NSS. The surviving patients have normal renal
      function, although two patients require medical management of hypertension.
      CONCLUSIONS: Our experience suggests that repeat NSS for local recurrence of FH
      bilateral Wilms tumor is feasible and affords acceptable oncologic outcome with
      preservation of renal function. However, more aggressive therapy may be required
      for patients whose recurrence has blastemal-predominant histology, given the poor
      outcome for these patients in our series.

PMID- 24439601
TI  - Inter-rater reliability of surgical reviews for AREN03B2: a COG renal tumor
      committee study.
AB  - PURPOSE: The Children's Oncology Group (COG) renal tumor study (AREN03B2)
      requires real-time central review of radiology, pathology, and the surgical
      procedure to determine appropriate risk-based therapy. The purpose of this study
      was to determine the inter-rater reliability of the surgical reviews. METHODS: Of
      the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood
      vessel involvement, spill, rupture, and lymph node involvement was selected for
      analysis. The surgical assessment was then performed independently by two blinded
      surgical reviewers and compared to the original assessment, which had been
      completed by another of the committee surgeons. Variables assessed included
      surgeon-determined local tumor stage, overall disease stage, type of renal
      procedure performed, presence of tumor rupture, occurrence of intraoperative
      tumor spill, blood vessel involvement, presence of peritoneal implants, and
      interpretation of residual disease. Inter-rater reliability was measured using
      the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value). RESULTS:
      Local tumor stage correlated in all 3 reviews except in one case (Kappa=0.9775,
      p<0.001). Similarly, overall disease stage had excellent correlation (0.9422,
      p<0.001). There was strong correlation for type of renal procedure (0.8357,
      p<0.001), presence of tumor rupture (0.6858, p<0.001), intraoperative tumor spill
      (0.6493, p<0.001), and blood vessel involvement (0.6470, p<0.001). Variables that
      had lower correlation were determination of the presence of peritoneal implants
      (0.2753, p<0.001) and interpretation of residual disease status (0.5310,
      p<0.001). CONCLUSION: The inter-rater reliability of the surgical review is high
      based on the great consistency in the 3 independent review results. This analysis
      provides validation and establishes precedent for real-time central surgical
      review to determine treatment assignment in a risk-based stratagem for multimodal
      cancer therapy.

PMID- 24439602
TI  - Targeting Aurora kinase-A downregulates cell proliferation and angiogenesis in
      neuroblastoma.
AB  - PURPOSE: Aurora kinase A (AURKA) overexpression is associated with poor prognosis
      in neuroblastoma and has been described to upregulate VEGF in gastric cancer
      cells. However, the exact role of AURKA in the regulation of neuroblastoma
      tumorigenesis remains unknown. We hypothesize that AURKA-mediated stabilization
      of N-Myc may affect VEGF expression and angiogenesis in neuroblastoma. Therefore,
      we sought to determine whether inhibition of AURKA modulates neuroblastoma
      angiogenesis. METHODS: Cell viability and anchorage-independent growth were
      determined after silencing AURKA or after treatment with MLN8237, AURKA
      inhibitor. Immunofluorescence was used to determine N-Myc localization. Human
      umbilical vein endothelial cells (HUVECs) were used to assess angiogenesis in
      vitro. Real time-PCR and ELISA were performed to determine VEGF transcription and
      secretion, respectively. RESULTS: Knockdown of AURKA significantly reduced cell
      proliferation and inhibited anchorage-independent growth. It also decreased N-Myc
      protein levels and nuclear localization. AURKA inhibition also decreased HUVECs
      tubule formation along with VEGF transcription and secretion. Similarly, MLN8237
      treatment decreased neuroblastoma tumorigenicity in vitro. CONCLUSIONS: Our
      findings demonstrate that AURKA plays a critical role in neuroblastoma
      angiogenesis. AURKA regulates nuclear translocation of N-Myc in neuroblastoma
      cells, thus potentially affecting cell proliferation, anchorage-independent cell
      growth, and angiogenesis. Targeting AURKA might provide a novel therapeutic
      strategy in treating aggressive neuroblastomas.

PMID- 24439603
TI  - A review of 218 pediatric cases of hepatocellular carcinoma.
AB  - PURPOSE: This study evaluates the incidence trends and clinical outcomes of
      children with hepatocellular carcinoma (HCC) and assesses factors predictive of
      patient survival. METHODS: The Surveillance, Epidemiology, and End Results
      registry was queried from 1973 to 2009 for all patients between ages 0 and 19
      with primary HCC. Demographics, tumor histology, surgical intervention, and
      patient survival were collected. RESULTS: Overall, 218 patients were identified.
      The annual age-adjusted incidence was 0.05 cases per 100,000 in 2009.
      Fibrolamellar subtype tumors were exclusive to children >5years old and exhibited
      greater survival compared to non-fibrolamellar subtype (57% vs. 28%,
      respectively, p=0.002). Tumor extirpation for patients with resectable disease
      significantly improved overall survival at 5years compared to no surgery (60% vs.
      0%, respectively, p<0.0001). Overall 5-, 10- and 20-year survival for the entire
      cohort was 24%, 23%, and 8%, respectively. Independent prognostic factors of
      lower mortality according to multivariate analysis were surgical resection
      (hazard ratio (HR)=0.18), non-Hispanic ethnicity (HR=0.52), and local disease at
      presentation (HR=0.46). CONCLUSION: Over the past four decades, the incidence of
      HCC has remained relatively stable. Children of Hispanic ethnicity have high
      mortality rates. However, HCC resection for curative intent significantly
      improves outcomes.

PMID- 24439604
TI  - "Trap-door" and "clamshell" surgical approaches for the management of pediatric
      tumors of the cervicothoracic junction and mediastinum.
AB  - BACKGROUND/PURPOSE: For pediatric tumors of the cervicothoracic junction, an
      isolated cervical or thoracic surgical approach provides insufficient exposure
      for achieving complete resection. We retrospectively examined "trap-door" and
      "clamshell" pediatric thoracotomies as a surgical approach to these tumors.
      METHODS: We searched our database for pediatric patients with cervicothoracic
      tumors who underwent clamshell or trap-door thoracotomy between 1991 and 2013,
      reviewing tumor characteristics, surgical technique, completeness of resection,
      morbidity, and outcome. RESULTS: Trap-door (n=13) and clamshell (n=4)
      thoracotomies were performed for neuroblastoma (n=9), non-rhabdomyosarcoma soft
      tissue sarcoma (n=4), germ cell tumor (n=2), rhabdomyosarcoma (n=1), and
      neuroendocrine small cell carcinoma (n=1). Fourteen of these cervicothoracic
      tumors were primary, and three were metastatic. Gross total resection was
      achieved in 15 patients (94%). Operative complications included vocal cord
      paralysis (n=2), mild upper-extremity neuropraxia (n=2), and hemidiaphragm
      paralysis (n=1), All but one involved encased nerves. Overall survival was 61%
      for the series and 80% for patients with primary tumors. Eleven (73%) of 15
      patients who underwent gross total resection had no evidence of recurrence. Three
      patients with metastatic disease died of distant progression within 1.3years.
      CONCLUSIONS: Gross total resection of primary cervicothoracic tumors can be
      accomplished with specialized exposure in pediatric patients with minimal
      morbidity.

PMID- 24439605
TI  - Trauma surgeon becomes consultant: evaluation of a protocol for management of
      intermediate-level trauma patients.
AB  - PURPOSE: At our level 1 pediatric trauma center, 9-54 intermediate-level ("level
      2") trauma activations are received per month. Previously, the surgery team was
      required to respond to and assume responsibility for all patients who had "level
      2" trauma activations. In 8/2011, we implemented a protocol where the emergency
      room (ER) physician primarily manages these patients with trauma consultation for
      surgical evaluation or admission. The purpose of this study was to prospectively
      evaluate the effects of the new protocol to ensure that patient safety and
      quality of care were maintained. METHODS: We compared outcomes of patients
      treated PRE-implementation (10/2010-7/2011) and POST-implementation (9/2011
      5/2012), including surgeon consultation rate, utilization of imaging and
      laboratory testing, ER length of stay, admission rate, and missed injuries or
      readmissions. Statistical analysis included chi-square and Student's t-test.
      RESULTS: We identified 472 patients: 179 in the PRE and 293 in the POST period.
      The populations had similar baseline clinical characteristics. The surgical
      consultation rate in the POST period was only 42%, with no missed injuries or
      readmissions. The ER length of stay did not change. However, in the POST period
      there were significant decreases in the admission rate (73% to 44%) and the mean
      number of CT scans (1.4 to 1), radiographs (2.4 to 1.7), and laboratory tests
      (5.1 to 3.3) ordered in the emergency room (all p<0.001). CONCLUSION:
      Intermediate-level pediatric trauma patients can be efficiently and safely
      managed by pediatric emergency room physicians, with surgical consultation only
      as needed. The protocol change improved resource utilization by decreasing
      testing and admissions and streamlining resident utilization in an era of reduced
      duty hours.

PMID- 24439606
TI  - Are CT scans obtained at referring institutions justified prior to transfer to a
      pediatric trauma center?
AB  - PURPOSE: To assess whether pediatric trauma patients initially evaluated at
      referring institutions met Massachusetts statewide trauma field triage criteria
      for stabilization and immediate transfer to a Pediatric Trauma Center (PTC)
      without pre-transfer CT imaging. METHODS: A 3-year retrospective cohort study was
      completed at our level 1 PTC. Patients with CT imaging at referring institutions
      were classified according to a triage scheme based on Massachusetts statewide
      trauma field triage criteria. Demographic data and injury profile characteristics
      were abstracted from patient medical records and our pediatric trauma registry.
      RESULTS: A total of 262 patients with 413 CT scans were reviewed from 2008 to
      2011. 172 patients scanned (66%, 95% CI: 60%, 71%) met criteria for immediate
      transfer to a pediatric trauma center. Notably, 110 scans (27% of the total
      performed at referring institutions) were duplicated within four hours upon
      arrival to our PTC. GCS score <14 (45%) was the most common requirement for
      transfer, and CT scan of the head was the most frequent scan obtained (53%).
      CONCLUSION: The majority of pediatric trauma patients were subjected to CT scans
      at referring institutions despite meeting Massachusetts trauma triage guidelines
      that call for stabilization and immediate transfer to a pediatric trauma center
      without any CT imaging.

PMID- 24439607
TI  - Is the Trauma Mortality Prediction Model (TMPM-ICD-9) a valid predictor of
      mortality in pediatric trauma patients?
AB  - BACKGROUND/PURPOSE: Researchers are constantly challenged to identify optimal
      mortality risk adjustment methodologies that perform accurately in pediatric
      trauma patients. This study evaluated the new Trauma Mortality Prediction Model
      (TMPM-ICD-9) in pediatric trauma patients. METHODS: Data were analyzed on 107,104
      pediatric trauma patients included in the NTDB(r) in 2010 who had both a valid
      ISS and probability of death using TMPM-ICD-9. Discrimination was compared using
      the area under the receiver operator characteristic curve (AUC) and by age, blunt
      vs penetrating, intent, Glasgow Coma Scale (GCS), and number of injuries.
      RESULTS: The AUC for TMPM-ICD-9 demonstrated excellent discrimination in
      predicting mortality versus ISS overall, 11 to 17years of age (0.96 vs 0.93), by
      injury type, intent, and in the lowest GCS scores. The TMPM-ICD-9 showed superior
      discrimination over ISS in patients with more than two injuries. CONCLUSIONS: The
      TMPM demonstrated superior discrimination compared to ISS. The TMPM shows promise
      of a much needed and simple to use risk adjustment tool with application to both
      adult and pediatric patients. Researchers should continue to validate this tool
      in robust pediatric data sets.

PMID- 24439608
TI  - Infant car safety seats and risk of head injury.
AB  - BACKGROUND/PURPOSE: We observed a high incidence of traumatic brain injuries
      (TBI) in properly restrained infants involved in higher speed motor vehicle
      crashes (MVCs). We hypothesized that car safety seats are inadequately protecting
      infants from TBI. METHODS: We retrospectively queried scene crash data from our
      State Department of Transportation (2007-2011) and State Department of Public
      Health data (2000-2011) regarding infants who presented to a trauma center after
      MVC. RESULTS: Department of Transportation data revealed 94% of infants in MVCs
      were properly restrained (782/833) with average speed of 44.6 miles/h when there
      was concern for injury. Department of Public Health data showed only 67/119
      (56.3%) of infants who presented to a trauma center after MVC were properly
      restrained. Properly restrained infants were 12.7 times less likely to present to
      a trauma center after an MVC (OR=12.7, CI 95% 5.6-28.8, p<0.001). TBI was
      diagnosed in 73/119 (61.3%) infants; 42/73 (57.5%) properly restrained, and 31/73
      (42.5%) improperly/unrestrained (p=0.34). Average head abbreviated injury scale
      was similar for properly restrained (3.2+/-0.2) and improperly/unrestrained
      infants (3.5+/-0.2, p=0.37). CONCLUSION: Car safety seats prevent injuries.
      However, TBI is similar among properly restrained and improperly/unrestrained
      infants involved in higher speed MVCs who present to a trauma center.

PMID- 24439609
TI  - Prospective observational study with an abbreviated protocol in the management of
      blunt renal injury in children.
AB  - BACKGROUND: There are no published management schemes for blunt renal injuries.
      We are conducting a 2-center prospective observational study with a fixed
      management scheme. METHODS: Children with CT proven renal injuries were enrolled
      with permission. Ambulation is allowed when able regardless of grade. Discharge
      occurs when tolerating a diet and pain is controlled regardless of hematuria.
      Urinalysis occurs at follow up in 2-4weeks and repeated as indicated. RESULTS:
      Between 9/2008 and 9/2012, 70 patients were enrolled. Mean age was 11.8years (3
      17), and 70% were male. The mean grade of injury was 2.8+/-1.1 [1-5]. One
      nephrectomy (1.4%) was performed for a grade 5 injury. Other renal interventions
      included an embolization for the hilar bleed and one cystotomy for a clot. Mean
      LOS was 2.9days+/-2.4days. In patients without other major injury, LOS was 1.9+/
      1.7days (0.4-8days). There were 5 (7%) readmissions: 3 for pain, 1 for hematuria,
      and 1 for a bladder clot. 58 patients (83%) gave urinalysis samples at initial
      follow up (med 18days), where 31 (53%) were positive for blood. CONCLUSIONS:
      Children with blunt renal injury may benefit from management without strict
      bedrest guidelines. Hematuria appears to have little influence on recovery.

PMID- 24439610
TI  - Operationalizing quality improvement in a pediatric surgical practice.
AB  - BACKGROUND/PURPOSE: Quality improvement (QI) is critical to enhancing patient
      care. It is necessary to prioritize which QI initiatives are relevant to one's
      institution and practice, as implementation is resource-intensive. We have
      developed and implemented a streamlined process to identify QI opportunities in
      our practice. METHODS: We designed a web-based Pediatric and Infant Case Log and
      Outcomes (PICaLO) instrument using Research Electronic Data Capture (REDCapTM) to
      record all surgical procedures for our practice. At the time of operation, a
      surgeon completes a case report form. An administrative assistant enters the data
      in PICaLO within 5-7days. Outcomes such as complications, deaths, and
      "occurrences" (readmissions, reoperations, transfers to ICU, ER visit, additional
      clinic visits) are recorded at the time of encounter, during M & M Conferences,
      and during follow-up clinic visits. Variables were chosen and defined based on
      national standards from the American College of Surgeons (ACS) National Surgical
      Quality Improvement Program (NSQIP), and Patient Based Learning Log. Occurrences
      are queried for potential QI initiatives. RESULTS: In 2012, 3597 patients were
      entered, totaling 5177 procedures. There were 220 complications, 278 occurrences,
      and 16 deaths. Specific QI opportunities were identified and put into place.
      CONCLUSION: Data on procedures and outcomes can be collected effectively in a
      pediatric surgery practice to delineate pertinent QI initiatives. PICaLO is
      recognized by the American Board of Surgery as a mechanism to meet Maintenance of
      Certification 4 criteria.

PMID- 24439611
TI  - Enhancing NSQIP-Pediatric through integration with the Pediatric Health
      Information System.
AB  - PURPOSE: We implemented and validated a linkage algorithm for cases in both the
      National Surgical Quality Improvement Program-Pediatric (NSQIP-Peds) and the
      Pediatric Health Information System (PHIS) to investigate healthcare utilization
      during the first post-operative year. METHODS: NSQIP-Peds and PHIS cases from our
      institution who were operated on between January 2010 and September 2011 were
      matched on gender and dates of birth, admission, and discharge. Rates of true
      matches were validated using medical records. We examined rates of emergency
      department (ED) visits, hospital readmissions, potentially preventable
      readmissions (PPR), and hospital charges within one year of the NSQIP-Peds
      encounter. RESULTS: Of the 2,409 NSQIP-Peds and 61,147 PHIS records, 93.6% met
      match criteria with 92.5% being true matches. Post-operative ED visit rates were
      7.8% within 30days, 17.2% between 31-180days, and 18.1% between 181-365days.
      Readmission rates were 5.5% within 30days, 9.3% between 31-180days, and 8.4%
      between 181-365days. In patients undergoing inpatient procedures, 10.6% had
      readmissions within 30days, and 23.7% had readmissions within 365days that were
      potentially preventable. CONCLUSIONS: Using indirect identifiers, a linked NSQIP
      Peds-PHIS dataset demonstrated high rates of ED visits, readmissions, and PPR in
      the first post-operative year. This dataset may provide a more comprehensive way
      to study health care utilization and clinical outcomes.

PMID- 24439612
TI  - Transumbilical endoscopic surgery for incarcerated inguinal hernias in infants
      and children.
AB  - PURPOSE: To describe transumbilical laparoscopic herniorrhaphy after unsuccessful
      attempted manual reduction of incarcerated inguinal hernias in infants and
      children. METHODS: In our two hospitals, two-trocar transumbilical endoscopic
      surgery (TUES) is the standard technique used to repair incarcerated inguinal
      hernias in infants and children. Seventeen patients (aged 8months to 2.5years;
      median, 15months; 15 boys, 2 girls) with incarcerated inguinal hernias underwent
      urgent laparoscopy after unsuccessful attempted manual reduction. Two 3- or 5-mm
      trocars were inserted into the abdomen through two intraumbilical incisions,
      under laparoscopic guidance. The hernia was reduced by combined external manual
      pressure and internal pulling with bowel forceps. After inspection of the bowel,
      a round needle with a 2-0 nonabsorbable suture was introduced into the peritoneal
      cavity through the anterior abdominal wall near the internal inguinal ring. The
      hernial orifice was closed with an extraperitoneal purse-string suture around the
      internal inguinal ring, and tied with an intraperitoneal knot. A similar
      procedure was performed on the contralateral side if the processus vaginalis was
      patent. RESULTS: The TUES procedure was successful in all patients. No
      conversions to open surgery were required. The mean operating time was 30min
      (range, 25-40min). All patients were discharged on the second postoperative day.
      No complications such as postoperative bleeding, hydrocele, or scrotal edema were
      observed. The mean follow-up period was 15months. No cases of testicular atrophy,
      hypotrophy, or hernia recurrence were reported. CONCLUSIONS: Our preliminary
      experience with using TUES for the treatment of incarcerated inguinal hernias in
      infants and children had satisfactory outcomes. This technique appeared to be
      safe, effective, and reliable, and had excellent cosmetic results.

PMID- 24439613
TI  - Perineal hypospadias: the Bilateral Based (BILAB) skin flap technique.
AB  - PURPOSE: The purpose of this study was to present the "bilateral based skin flap
      (BILAB) technique" for patients with perineal hypospadias associated with severe
      deep chordee and report the follow up. OPERATIVE PRINCIPLE: The short urethral
      plate is incised, the hypoplastic corpus spongiosum excised, the glans split in
      the midline, and a healthy urethral plate is reconstructed from the lateral
      penile skin and foreskin to the tip of the glans. PATIENTS AND METHODS: Between
      January 2005 and December 2011, the BILAB technique was performed in 68 patients
      with perineal hypospadias associated with severe chordee as a one or two stage
      repair. The records of 63 patients who maintained regular follow up were
      reviewed. The new urethra was reconstructed from the new urethral plate during
      the same setting in 26 patients. The remaining 37 patients had the urethroplasty
      performed 3-6 months later as a two stage repair. Patient age ranged from 8
      months and 2 years (mean 10 months). Follow-up period ranged from 18 months to 8
      years (mean 43 months). RESULTS: Satisfactory results were obtained in 54
      patients (85%). Two children developed diverticula, two patients developed glans
      dehiscence, one child developed fistula, and one child had complete wound
      dehiscence, and urethroplasty was successfully reconstructed 6 months later.
      Three patients developed scar contraction 6-12 months after surgery. This was
      corrected by excision of the scarred intermediate layer. CONCLUSIONS: The BILAB
      technique is a reliable technique for patients with perineal hypospadias. It
      produces slit like meatus at the tip of the glans. The surgeon may decide intra
      operatively whether to complete the urethroplasty in one or two stages. Long term
      follow up until puberty is being carried out.

PMID- 24439614
TI  - Effects of thyroid hormone on the GH signal transduction pathway.
AB  - BACKGROUND/AIM: The importance of thyroid hormone on growth and development in
      children is well recognized. In addition, linear growth is highly dependent on
      the response of peripheral tissues to growth hormone, a process known as GH
      sensitivity, but little is known about the possible effects of T4 on this
      process. METHODS: We determined the effect of stimulation with recombinant human
      GH (rhGH; 200 ng/mL) alone or in combination with two different concentrations of
      T4 (250 nM and 500 nM for 24 h) on JAK2 and STAT5 activation in skin fibroblast
      cultures obtained from prepubertal boys with normal height. RESULTS: JAK2 and
      STAT5 were activated under co-incubation with T4 (at both concentrations) and
      rhGH in the non-nuclear fraction of the fibroblasts. In addition, after 24h of co
      incubation with rhGH and T4 (500 nM), we observed an increase in phospho-STAT5 in
      the nuclear fraction, when compared to GH and T4 stimulation alone. This effect
      was not observed when the fibroblasts were co-incubated with GH and the lower
      concentration of T4 (250 nM). CONCLUSION: Combined stimulation with GH and T4 at
      a concentration of 500 nM increases synergistically nuclear phospho-STAT5 in skin
      fibroblasts, which may amplify tissue sensitivity to GH. These findings may help
      to explain the effect of T4 administration on growth velocity in some children
      with idiopathic short stature.

PMID- 24439615
TI  - Brief report: Assessing dispositional optimism in adolescence--factor structure
      and concurrent validity of the Life Orientation Test--Revised.
AB  - Dispositional optimism is an individual difference promoting psychosocial
      adjustment and well-being during adolescence. Dispositional optimism was
      originally defined as a one-dimensional construct; however, empirical evidence
      suggests two correlated factors in the Life Orientation Test - Revised (LOT-R).
      The main aim of the study was to evaluate the dimensionality of the LOT-R. This
      study is the first attempt to identify the best factor structure, comparing
      congeneric, two correlated-factor, and two orthogonal-factor models in a sample
      of adolescents. Concurrent validity was also assessed. The results demonstrated
      the superior fit of the two orthogonal-factor model thus reconciling the one
      dimensional definition of dispositional optimism with the bi-dimensionality of
      the LOT-R. Moreover, the results of correlational analyses proved the concurrent
      validity of this self-report measure: optimism is moderately related to indices
      of psychosocial adjustment and well-being. Thus, the LOT-R is a useful, valid,
      and reliable self-report measure to properly assess optimism in adolescence. 

PMID- 24439616
TI  - The role of emotion identification skill in the formation of male and female
      friendships: a longitudinal study.
AB  - The present study explored the relationship between emotion identification skill
      (EIS) and friendships in adolescence. Students from five Australian high schools
      completed questionnaires annually from Grade 8 to Grade 12 including subjective
      measures of EIS and a peer-based objective measure of social functioning (e.g.,
      friendship nominations). The total sample of participants was 795 (406 males; 389
      females) with 468 (225 males; 243 females) completing questionnaires in Grade 12.
      EIS in early adolescence was predictive of friendships for females in late
      adolescence. Specifically, girls starting out with low EIS in Grade 8 tended to
      have fewer female friendships and more male friendships in Grade 12. There were
      no effects for males. Lower initial EIS was associated with significant
      improvements in awareness over time, but these improvements had no effect on
      friendships in Grade 12. The EIS that girls enter high school with may influence
      their friendship composition into late adolescence. 

PMID- 24439617
TI  - The relationship of thought suppression and recent rape to disordered eating in
      emerging adulthood.
AB  - This study utilizes a prospective design to examine the interaction of recent
      rape/attempted rape with individual differences in thought suppression on
      increases in disordered eating symptoms during late adolescence/emerging
      adulthood. Thought suppression is the attempt to suppress unwanted thoughts. We
      propose that emerging adult women who have experienced recent rape/attempted rape
      and tend to use thought suppression as a coping mechanism are at risk for
      increases in disordered eating. 319 women completed the Eating Disorder
      Examination Questionnaire, the Sexual Experiences Survey, the Childhood Trauma
      Questionnaire, and the White Bear Thought Suppression Inventory in their first
      month of college and three months later. The experience of recent rape/attempted
      rape in the three months prior to the assessment accounted for unique variance in
      disordered eating at Time 2. Levels of thought suppression assessed at Time 1
      significantly moderated the influence of recent rape/attempted rape on disordered
      eating at Time 2. 

PMID- 24439618
TI  - Internet use and addiction among Finnish adolescents (15-19 years).
AB  - This study investigates Internet use among Finnish adolescents (n = 475)
      combining qualitative and quantitative research. Internet use was evaluated using
      the Internet Addiction Test (Young, 1998a, 1998b). The data was divided into
      three parts according to the test scores: normal users (14.3%), mild over-users
      (61.5%), and moderate or serious over-users (24.2%). The most common reason for
      use was having fun. While half the students reported disadvantages associated
      with their use, further qualitative analysis revealed that students with serious
      overuse did not report any harm caused by using the Internet. As disadvantages of
      using the Internet, students reported that it is time-consuming and causes
      mental, social, and physical harm and poor school attendance. Four factors of
      Internet addiction were found, and for two of them, a statistical difference
      between females and males was found.

PMID- 24439619
TI  - Discussions of adolescent sexuality in news media coverage of the HPV vaccine.
AB  - Given the sexually transmitted nature of human papillomavirus (HPV), some worry
      the HPV vaccine will create a false sense of security and promote adolescent
      sexual activity. Media coverage of vaccines can influence social norms, parental
      attitudes, and vaccine acceptance; in this paper we examine U.S. news media
      messages related to sexuality and HPV vaccination. Drawing on a structured
      analysis of 447 articles published during 2005-2009, we qualitatively analyzed a
      purposive sample of 49 articles discussing adolescent health behaviors related to
      HPV vaccination. Commonly, articles discussed vaccination in the context of
      abstinence-only versus comprehensive sexual health education; cited research
      findings to support vaccination or sex education; argued against connecting
      vaccination to promiscuous behavior; but included fear-inducing messages. Media
      messages concerning health behaviors related to HPV vaccination tended to support
      government and parental involvement in sex education, and dismiss concerns
      linking vaccination to sexual activity, while also presenting the vaccine as
      lifesaving. 

PMID- 24439620
TI  - Associations among sleep, daily experiences, and loneliness in adolescence:
      evidence of moderating and bidirectional pathways.
AB  - The present study examined the dynamic associations among daily stress levels,
      affect, and objective sleep quality in adolescence. We also explored loneliness
      as a potential moderator of these associations. Seventy-eight adolescents
      participated over three days. They completed diary reports of stressful
      experiences and affect five times a day while wearing an actigraph to obtain
      objective measurement of sleep. They also provided self-reports of loneliness.
      High daily stress was associated with shorter sleep duration. Models testing
      bidirectional associations indicated that prior day stress was associated with
      shorter sleep duration, but poor sleep duration and sleep efficiency were also
      associated with greater stress the next day. Loneliness was a significant
      moderator of the associations between daily stress and sleep duration and latency
      such that lonely individuals had shorter sleep durations and sleep latencies
      after particularly stressful days. Results suggest daily dynamic associations
      among loneliness, daily stress, and objective measures of adolescent sleep. 

PMID- 24439621
TI  - Substance use predictors of victimization profiles among homeless youth: a latent
      class analysis.
AB  - Although a substantial body of literature demonstrates high prevalence of street
      victimization among homeless youth, few studies have investigated the existence
      of victimization classes that differ on the type and frequency of victimization
      experienced. Nor do we know how substance use patterns relate to victimization
      classes. Using latent class analysis (LCA), we examined the existence of
      victimization classes of homeless youth and investigated substance use predictors
      of class membership utilizing a large purposive sample (N=601) recruited from
      homeless youth-serving host agencies in three disparate regions of the U.S.
      Results of the LCA suggest the presence of three distinct victimization profiles 
      youth fit into a low-victimization class, a witness class, or a high
      victimization class. These three victimization classes demonstrated differences
      in their substance use, including rates of substance abuse/dependence on alcohol
      and/or drugs. The presence of distinct victimization profiles suggests the need
      for screening and referral for differential services. 

PMID- 24439623
TI  - Trust and social reciprocity in adolescence--a matter of perspective-taking.
AB  - Changes in social behaviour from childhood to adulthood have been suggested to be
      driven by an increased sensitivity to others' perspectives. Yet, the link between
      perspective-taking and social processes, such as trust and reciprocity, has
      rarely been investigated during adolescence. Using two trust games with a
      cooperative and an unfair counterpart and an online perspective-taking task with
      50 adolescents, we show that those with a higher perspective-taking tendency
      demonstrate greater trust towards others and higher levels of trust during
      cooperative interactions. Both low and high perspective-takers adapted their
      levels of trust in response to unfair behaviour. However, high perspective-takers
      reduced their trust more drastically and showed more malevolent and less
      benevolent tit-for-tat when they were treated unfairly by their counterpart. The
      findings suggest that a higher perspective-taking tendency in adolescence is
      associated with specific mechanisms of trust and reciprocity, as opposed to
      undifferentiated increases in positive social behaviour towards others. 

PMID- 24439622
TI  - Pubertal timing and vulnerabilities to depression in early adolescence:
      differential pathways to depressive symptoms by sex.
AB  - Although research implicates pubertal processes in the emergence of the sex
      difference in depression during adolescence, few studies have examined how
      cognitive and affective vulnerabilities influence the effect of pubertal timing
      on depressive symptoms. The current study prospectively examined whether early
      pubertal timing predicted increases in depressive symptoms among adolescents with
      more negative cognitive styles and lower emotional clarity, and whether this risk
      was specific to adolescent girls. In a diverse sample of 318 adolescents, early
      pubertal timing predicted increases in depressive symptoms among adolescent boys
      and girls with more negative cognitive styles and adolescent girls with poor
      emotional clarity. These findings suggest that earlier pubertal maturation may
      heighten the risk of depression for adolescents with pre-existing vulnerabilities
      to depression, and that early maturing adolescent girls with lower levels of
      emotional clarity may be particularly vulnerable to depressive symptoms,
      representing one pathway through which the sex difference in depression may
      emerge. 

PMID- 24439624
TI  - Latino and European American early adolescents' exposure to music with substance
      use references: examining parent-child communication as a moderator.
AB  - This study hypothesized that frequent exposure to and attention to music with
      substance-use references would be indirectly related to alcohol, cigarette, or
      marijuana use through pro-substance-use beliefs (e.g., norms, outcome
      expectancies, and refusal efficacy). Parent-child communication, however, would
      attenuate such associations, which would differ by ethnicity. Multigroup
      mediation and moderation analyses were conducted, using cross-sectional survey
      data from 253 Latino and 308 European American 6th-8th grades students. For
      Latino and European American early adolescents, best-friend-injunctive norms and
      weak refusal efficacy were significant mediators, but not positive outcome
      expectancies. Descriptive norms were a significant mediator, but only for
      European American early adolescents. Although targeted parent-child communication
      and parental mediation did not moderate the associations between the music
      exposure variables and the pro-substance-use beliefs variables, targeted parent
      child communication attenuated the association between listening to favorite
      songs and alcohol consumption. Parental mediation attenuated the association
      between attention to music and alcohol consumption. 

PMID- 24439625
TI  - Prevalence and correlates of depressive symptoms among in-school adolescents in a
      rural district in southwest Nigeria.
AB  - This study was conducted to assess the prevalence and correlates of depressive
      symptoms among in-school adolescents in a rural district in southwest Nigeria. A
      cross-sectional survey involving 1713 adolescents from four private and three
      public secondary schools were selected using a stratified cluster sampling
      technique. Patient Health Questionnaire (PHQ)-9, with a maximum score of 27, was
      used to assess the presence (score >= 5) and severity (score >= 15) of the
      symptoms of depression. Multiple logistic regression was used to identify the
      correlates. The prevalence was 21.2%; 5.1% of the respondents had moderately
      severe to severe depression. Significant predictors included "not living with
      parents" (OR = 1.69; 95%CI, 1.14-2.38), not participating in sports (OR = 1.45;
      95%CI; 1.11-1.92), a large number of siblings (OR = 1.69; 95%CI; 1.11-2.63), and
      a change in place of residence (OR = 1.46; 95%CI, 1.13-1.88). A need exists to
      plan and implement health education measures to reduce the burden of the disease.

PMID- 24439626
TI  - Teachers and the religious socialization of adolescents: facilitation of
      meaningful religious identity formation processes.
AB  - This study investigated the effects of religious education on student religious
      identity over and above parent religiosity by examining student perceptions of
      two aspects of teacher functioning: teacher caring and teacher as role-model. We
      posited that effects of these variables on students' religious identity are
      mediated by student perceptions that the school provides a non-alienating
      religious atmosphere and meaningful religious studies. Participants were 2691
      male and female students (grades 9-12) in 152 classes of 25 schools from the
      Jewish public-religious sector in Israel. Results indicate that in addition to
      their parents' religiosity, adolescents' perceptions of their teachers as role
      models and their religious studies as meaningful are important variables
      affecting their religious identity. Moreover, this research suggests that
      religious identity formation processes flourish in an educational environment
      which students perceive as accommodating religious exploration. 

PMID- 24439627
TI  - A prospective study of adolescent risk and protective factors for problem
      gambling among young adults.
AB  - There is a paucity of research examining prospective predictors of problem
      gambling. The current study utilised a large longitudinal data set (N = 2328) to
      examine a large range of adolescent risk and protective factors for problem
      gambling in young adulthood. These risk and protective factors covered the
      domains of the community, family, school, peer group and individual. Numerous
      predictors associated with the family, school and peer-individual were
      statistically significant in analyses adjusted for gender and age. However, in
      the fully adjusted multivariate analyses, only two predictors were statistically
      significant. Within this model, gender (female) was associated with a reduced
      risk of young adult problem gambling, while family rewards for prosocial
      involvement moderated the risk relationship between adolescent alcohol use and
      young adult problem gambling. These findings highlight the importance of
      adolescent alcohol use and family environment as potentially modifiable
      predictors of young adult problem gambling.

PMID- 24439628
TI  - Efficacy of spherical aberration correction based on contact lens power.
AB  - PURPOSE: To investigate the efficacy of spherical aberration (SA) correction with
      aspheric contact lenses (aspheric lenses) based on lens power, and compare the
      results with those of spherical contact lenses (spherical lenses). METHODS:
      Ocular higher-order aberrations were measured with a wavefront sensor, in 11
      myopic subjects wearing an aspheric lens (Medalist Fresh fit (PUREVISION 2 HD);
      Bausch+Lomb) or a spherical lens (ACUVUE Oasys; Johnson & Johnson). Six different
      lens powers (-7.00 diopters (D), -5.00 D, -3.00 D, -1.00 D, +1.00 D, +3.00 D)
      were used for all subjects. The amount of SA correction from the contact lens at
      each power was calculated as the difference between SA with the contact lens on
      eye and SA of the eye alone. RESULTS: For the spherical lenses, SA correction was
      close to 0.00 MUm for the +1.00 D lens, became more positive as the labeled lens
      power increased and became more negative as the labeled lens power decreased. For
      the aspheric lenses, SA correction was consistent, from -0.15 to -0.05 MUm, for
      all lens powers except for the -1.00 D lens. SA correction for the spherical and
      aspheric lenses was significantly different at -7.00 D (p=0.040), -3.00 D
      (p=0.015), -1.00 D (p<0.001), +1.00 D (p=0.006), and +3.00 D (p<0.001) powers.
      CONCLUSION: An aspheric lens is capable of correcting SA at different lens
      powers, and has SA correction in the range of -0.15 to -0.05 MUm over a 6mm
      aperture.

PMID- 24439629
TI  - Duration of follow-up to diagnose hypospadias urethroplasty complications.
AB  - OBJECTIVE: We report the time when hypospadias urethroplasty complications (UC)
      were diagnosed postoperatively. METHODS: The time UC occurred after primary
      distal and proximal TIP and TIP reoperations was obtained from prospectively
      maintained databases in consecutive patients. UC included fistulas, glans
      dehiscences, meatal stenoses, neourethral strictures and diverticula. RESULTS: Of
      125 UC, 64% were diagnosed at the first postoperative visit and 81% were
      encountered within the first year after repair. Median time for diagnosis was 6
      months (1.5-95) for fistulas, meatal stenoses/urethra strictures, and
      diverticulum, versus 2 months (1 week-24 months) for glans dehiscence.
      CONCLUSIONS: The majority of UC are diagnosed at the first postoperative visit or
      within the first year following TIP hypospadias repair. Glans dehiscences are
      most often apparent by 2 months, whereas most fistulas and other UC are found by
      6 months. After 1 year, 14 boys without UC have to be followed indefinitely to
      diagnose each additional complication.

PMID- 24439630
TI  - Peristeen integrated transanal irrigation system successfully treats faecal
      incontinence in children.
AB  - OBJECTIVE: Faecal incontinence secondary to myelomeningocele, Hirschsprung
      disease, and anorectal anomalies remains a significant and common problem. We
      aimed to report our 5-year experience with the Peristeen trans-anal irrigation
      system (TAIS) to manage such children. PATIENTS AND METHOD: This study was a
      combination of a retrospective case note review and assessment using a validated
      quality of life questionnaire (QOL) to determine pre- and post-TAIS bowel
      function and continence. QOL scores and functional outcomes before and during
      TAIS use were compared using Wilcoxon matched pairs test (p < 0.05 significant).
      RESULTS: Twenty-four children (median age 6 years) were managed with the TAIS
      2006-2011 to treat faecal incontinence. Three did not tolerate the system. Median
      QOL scores in 20 out of 21 patients using TAIS demonstrated significant
      improvement in bowel management and continence. Two discontinued use due to
      failure to improve continence; one underwent the Malone antegrade continence
      enema (MACE) procedure and one returned to oral/rectal medications. Nineteen of
      24 patients (79%) continue to use TAIS. CONCLUSIONS: The Peristeen TAIS is an
      effective, safe, non-operative alternative to MACE in children with faecal
      incontinence, if initial compliance can be achieved.

PMID- 24439631
TI  - Re: 'which type of urethroplasty in failed hypospadias repair? An 8-year follow
      up'.

PMID- 24439632
TI  - Panic symptom clusters differentially predict suicide ideation and attempt.
AB  - Increasingly strong evidence links anxiety disorders in general and panic attacks
      in particular to suicidality. The underlying causes and specifics of this
      relation, however, remain unclear. The present article sought to begin addressing
      this question by clarifying the association between panic symptoms and
      suicidality. Data were sampled from the NESARC epidemiological data set from the
      US and analyzed as four independently, randomly selected subsets of 1000
      individuals using structural equation modeling analyses and replicating results
      across samples. Evidence is presented for four symptom clusters (cognitive
      symptoms, respiratory distress, symptoms of alpha and beta adrenergic activation)
      and the differential association of each with suicidal ideation and attempts.
      Symptoms of alpha adrenergic activation predicted prior suicide attempt whereas
      cognitive symptoms predicted prior suicidal ideation. These findings were
      independent of comorbid major depressive disorder. It is suggested that
      assessment of suicide risk in the community includes the presentation of
      cognitive symptoms and symptoms related to alpha adrenergic activation. 

PMID- 24439633
TI  - Does Harm Avoidance mediate effects of recollected parental bonding on mental
      distress in adulthood?
AB  - BACKGROUND: Adverse early life conditions such as perceived low quality of
      parental bonding increase vulnerability to stress and psychopathology in
      adulthood. However, the mechanisms by which perceptions of parental bonding
      translate into vulnerability are unclear and remain sparsely investigated in
      healthy populations. We proposed a model, in which the personality trait Harm
      Avoidance would mediate effects of recollected parental bonding during the first
      sixteen years of life on measures of perceived stress and mental distress
      severity in adulthood. METHOD: Five-hundred-eighteen adults (65.1 % women), aged
      18-53years, completed questionnaires of parental bonding, perceived stress, trait
      Harm Avoidance, and severity of mental distress. Direct and indirect effects
      mediated through trait Harm Avoidance were examined in a structural equation
      model. RESULTS: Under the causal assumptions of our proposed model, indirect
      effects of trait Harm Avoidance mediated the relationship between parental
      overprotection and severity of mental distress, while significantly attenuating
      the direct effects of parental care on severity of mental distress. Moreover,
      indirect effects of trait Harm Avoidance significantly attenuated the direct
      effects of parental overprotection and care on perceived stress. CONCLUSION: In
      this large sample of mentally healthy adults, recollected parental bonding was
      significantly associated with levels of perceived stress and severity of mental
      distress. The results from our proposed model further suggest that trait Harm
      Avoidance may be a developmental link, by which the quality of recollected
      parental bonding in childhood translates into adult vulnerability to stress and
      mental distress.

PMID- 24439634
TI  - [Arterio-arterial fistula between pulmonary and intercostal arteries--case report
      of "unilateral rib notching"].
AB  - The authors present a clinical case of a 35-year-old patient who was diagnosed
      with intercostal artery-to-pulmonary artery fistula and review the literature of
      systemic-to- pulmonary fistulae based on radiological findings of an exceptional
      case report. 

PMID- 24439635
TI  - Effects of FGF-2 and OP-1 in vitro on donor source cartilage for auricular
      reconstruction tissue engineering.
AB  - OBJECTIVE: Microtia is a congenital partial or total loss of the external ear
      with current treatment approaches involving autologous construction from costal
      cartilage. Alternatively, tissue engineering provides possible use of normal or
      microtia auricular chondrocytes harvested from patients. This study investigated
      effects in vitro of basic fibroblast growth factor (FGF-2) and osteogenic protein
      1 (OP-1) on human pediatric normal and microtia auricular chondrocytes and their
      potential proliferation and differentiation for cellular expansion. A working
      hypothesis was that FGF-2 promotes proliferation and OP-1 maintains an auricular
      phenotype of these cells. METHODS: Two patients, one undergoing otoplasty and one
      an ear construction, yielded normal and microtia auricular chondrocytes,
      respectively. The two donor sets of isolated chondrocytes were equally divided
      into four experimental cell groups. These were controls without added growth
      factors and cells supplemented with FGF-2, OP-1 or FGF-2/OP-1 combined. Cells
      were cultured 3, 5, 7, and 10 days (3 replicates/time point), counted and assayed
      by RT-qPCR to determine elastin and types II and III collagen gene expression.
      RESULTS: Compared to control counterparts, normal and microtia chondrocytes with
      OP-1 alone were similar in numbers and varied in elastin and types II and III
      collagen expression over all culture times. Compared to respective controls and
      chondrocyte groups with OP-1 alone, normal and microtia cell groups with FGF-2
      had statistically significant (p<0.05) enhanced proliferation and statistically
      significant (p<0.05) decreased elastin and types II and III collagen expression
      over 10 days of culture. CONCLUSIONS: FGF-2 effects on normal and microtia
      chondrocytes support its use for increasing cell numbers while OP-1 maintains a
      chondrocyte phenotype, otherwise marked by increasing type III collagen
      expression and cellular dedifferentiation to fibroblasts in culture.

PMID- 24439636
TI  - The effects of lavender aromatherapy on pain following needle insertion into a
      fistula in hemodialysis patients.
AB  - OBJECTIVE: This study sought to determine the effects of lavender aromatherapy on
      pain following needle insertion into a fistula in patients undergoing
      hemodialysis. METHOD: This is a randomized controlled clinical trial in which 92
      patients undergoing hemodialysis with arteriovenous fistulas were randomly
      divided into two groups. The experimental-group patients inhaled lavender essence
      with a concentration of 10% for 5 min during 3 hemodialysis sessions, while the
      control-group patients received aromatherapy free of lavender essence. RESULTS:
      The mean VAS pain intensity score in the experimental and control groups before
      the intervention was 3.78 +/- 0.24 and 4.16 +/- 0.32, respectively (p = 0.35).
      The mean VAS pain intensity score in the experimental and control groups after
      three aromatherapy sessions was 2.36 +/- 0.25 and 3.43 +/- 0.31, respectively (p
      = 0.009). CONCLUSION: Lavender aromatherapy may be an effective technique to
      reduce pain following needle insertion into a fistula in hemodialysis patients.

PMID- 24439637
TI  - High frequency TENS as a complement for pain relief in postoperative transition
      from epidural to general analgesia after pancreatic resection.
AB  - AIM: This study investigated the effect of high frequency transcutaneous electric
      nerve stimulation (TENS) as a pain relieving complementary therapy at the
      transition from epidural (EDA) to general analgesia after pancreatic surgery by
      horizontal, abdominal incision. METHOD: Fifty-five consecutive patients
      undergoing pancreatic resection were enrolled in the study and randomly assigned
      to active or sham TENS treatment. Twenty subjects were included in the analysis.
      Pain, quality of recovery and additional analgesia consumption were measured
      during the 24 h of transition from EDA to general analgesia. RESULTS: Additional
      analgesic consumption and pain estimations at 24 h after EDA termination differed
      between the two groups, but was not statistically significant. CONCLUSION: This
      study did not find support to reject use of high frequency TENS as complement
      during transition from EDA to general analgesia after major abdominal surgery
      with horizontal incision.

PMID- 24439638
TI  - CAM use in dermatology. Is there a potential role for honey, green tea, and
      vitamin C?
AB  - Complementary and alternative medicine (CAM) is a group of non-traditional
      medical practices that includes natural products, manipulations, and mind and
      body medicine. CAM use has grown and become popular among patients. In
      dermatology, honey, green tea, and vitamin C have been used as topical treatments
      for a variety of diseases. We performed a systematic review to explore the
      cutaneous effects of each of these three products. Honey's unique antibacterial,
      anti-inflammatory, and antioxidant properties were shown to contribute to wound
      healing, especially in ulcers and burns. Green tea, among many health benefits,
      demonstrated protection from ultraviolet-induced events, such as
      photoimmunosuppression and skin cancer growth. Vitamin C, known for its
      antioxidant properties and key role in collagen production, has been shown to
      produce positive effects on skin hyperpigmentation and aging. Future large well
      designed clinical trials are needed in order to further investigate the potential
      of these agents as dermatological therapies. 

PMID- 24439639
TI  - Prevalence of visits to massage therapists by the general population: a
      systematic review.
AB  - OBJECTIVE: To systematically review 12-month prevalence of visits to massage
      therapists by representative samples of the general population across countries.
      METHODS: Surveys reporting estimates of overall CAM use were included. Studies
      were identified via database searches. Study quality was assessed using a six
      item tool. RESULTS: Twenty-two surveys across six countries were included.
      Estimates for 12-month prevalence of visits to massage therapists by adults
      ranged from 0.4% to 20% and the median was 5.5%. Estimates for children were 0.3%
      3.8% (median 0.7%), while estimates for older adults were 1.5%-16.2% (median
      5.2%). 16 surveys (73%) met at least four of six quality criteria. CONCLUSIONS:
      This review summarises 12-month prevalence of visits to massage therapists in six
      countries (USA, UK, Canada, Australia, Singapore and South Korea). A small but
      significant percentage of these general populations visit massage therapists each
      year.

PMID- 24439640
TI  - Reiki therapy for postoperative oral pain in pediatric patients: pilot data from
      a double-blind, randomized clinical trial.
AB  - PURPOSE: To examine the effects of Reiki as an adjuvant therapy to opioid therapy
      for postoperative pain control in pediatric patients. METHODS: This was a double
      blind, randomized controlled study of children undergoing dental procedures.
      Participants were randomly assigned to receive either Reiki therapy or the
      control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid
      requirements, and side effects were assessed. Family members were also asked
      about perioperative care satisfaction. Multiple linear regressions were used for
      analysis. RESULTS: Thirty-eight children participated. The blinding procedure was
      successful. No statistically significant difference was observed between groups
      on all outcome measures. IMPLICATIONS: Our study provides a successful example of
      a blinding procedure for Reiki therapy among children in the perioperative
      period. This study does not support the effectiveness of Reiki as an adjuvant
      therapy to opioid therapy for postoperative pain control in pediatric patients.

PMID- 24439641
TI  - A randomized controlled trial of electroacupuncture at body acupoints and
      Fenglong for regulating serum lipids in dyslipidemic patients in Thailand.
AB  - The primary objective of this randomized, controlled, open-label study was to
      compare the efficacy of body acupuncture and Fenglong method in controlling serum
      lipids in patients with dyslipidemia in Thailand. Patients were randomized into
      two treatment groups (body acupuncture and Fenglong) and a control group. By the
      end of intervention period, serum lipid level in both treatment groups was
      significantly lower than its baseline value while in the control group serum
      lipid levels significantly increased during the same period. At follow-up visit,
      total cholesterol and LDL cholesterol were significantly lower in both treatment
      groups when compared to the control group. The effect of both acupuncture
      interventions was seen in both obese and non-obese patients. In conclusion, body
      acupuncture and Fenglong method have a positive impact on the regulation of serum
      lipids that is sustained after the treatment regardless of patient's baseline
      weight. 

PMID- 24439642
TI  - An integrative review of the literature on the chiropractic care of infants with
      constipation.
AB  - INTRODUCTION: Constipation compromises the health-related quality of life of
      children. Chiropractic is a popular alternative therapy for children with
      constipation. We performed this integrative review of the literature to inform
      clinical practice. METHODS: Our integrative review of the literature began with
      an examination of the databases Pubmed [1966-2013], MANTIS [1964-2013] and Index
      to Chiropractic Literature [1984-2013]. The search terms used were
      "constipation", "chronic constipation", and "bowel dysfunction" in the context of
      chiropractic. Inclusion criteria involved the care of children 0-18 years old
      published in the English language. RESULTS: We found 14 case reports, one case
      series, and one review of the literature. A number of chiropractic techniques
      were described with treatment varying according to the diagnosis, chief complaint
      and age of the patient. CONCLUSION: Our integrative review revealed the need for
      more research and theoretical development on the care of children with
      constipation.

PMID- 24439643
TI  - Integrative treatment modalities for stoke victims in Korea.
AB  - OBJECTIVES: To suggest and discuss an integrative medicine model for stroke
      patients, we introduce our experience in Korea, describe treatment modalities
      used for stroke in Korean medicine, and present safety data on integrative care.
      SUMMARY: For inpatients, integrative management is applied at the request of the
      primary physician with the consent of patients or their families. In the acute
      stage, neurologists or neurosurgeons take charge as the primary physicians.
      Korean medicine doctors cooperate as secondary physicians to the neurologists and
      neurosurgeons. After the acute stage, responsibilities are exchanged. The
      rehabilitation program is conducted under the supervision of rehabilitation
      medicine doctors. The most frequently used complementary and alternative medicine
      modalities are acupuncture (including manual acupuncture, electroacupuncture and
      intradermal acupuncture), moxibustion, herbal prescriptions, and acupuncture
      point injection. CONCLUSION: Based on our field experiences, we believe it is
      worthwhile to continue efforts to integrate complementary and alternative
      medicine and Western medicine.

PMID- 24439644
TI  - The effects of foot reflexology massage on anxiety in patients following coronary
      artery bypass graft surgery: a randomized controlled trial.
AB  - OBJECTIVE: To examine the effects of foot reflexology massage on anxiety in
      patients following CABG surgery. METHODS: In this randomized controlled trial, 80
      patients who met the inclusion criteria were conveniently sampled and randomly
      allocated to the experimental and control groups after they were matched on age
      and gender. On the days following surgery, the experimental group received foot
      reflexology massage on their left foot 20 min a day for 4 days, while the control
      group was given a gentle foot rub with oil for one minute. Anxiety was measured
      using the short-form of the Spielberger State-Trait Anxiety Inventory and the
      Visual Analogue Scale-Anxiety. RESULTS: Both measurement instruments confirmed a
      significant decrease in anxiety following the foot reflexology massage.
      CONCLUSION: The significant decrease in anxiety in the experimental group
      following the foot reflexology massage supports the use of this complementary
      therapy technique for the relief of anxiety.

PMID- 24439645
TI  - Sit, breathe, smile: effects of single and weekly seated Qigong on blood pressure
      and quality of life in long-term care.
AB  - Long-term care (LTC) facilities house individuals with diverse combinations of
      cognitive and physical impairments, and the practice of Seated Qigong eliminates
      common exercise barriers. This study hypothesized: 1) a single session would
      lower blood pressure (BP) and improve quality of life (QOL) in a generalized LTC
      population, and 2) these responses would be attenuated with chronic (weekly)
      Seated Qigong practice. Ten residents (6 female; 86 +/- 7 years) participated in
      1X/week Seated Qigong sessions for 10-weeks. BP and QOL were assessed pre- and
      post-session at baseline and following 5- and 10-weeks of Qigong. Systolic BP was
      significantly reduced immediately post-session after 10-weeks of Qigong (P =
      0.03), yet unchanged at baseline and after 5-weeks (all P > 0.05). Diastolic BP
      and QOL remained unchanged (P > 0.05). A session of Seated Qigong elicits a
      hypotensive response with exposure, supporting the notion that repeated sessions
      may provide advantageous health benefits. 

PMID- 24439646
TI  - Physicians' attitudes toward complementary and alternative medicine and their
      knowledge of specific therapies: 8-year follow-up at an academic medical center.
AB  - The purpose of this study was to determine changes in attitude toward
      complementary and alternative medicine (CAM) therapies and knowledge of specific
      CAM therapies among internists at our institution. We compared the results of a
      survey given in 2004 and 2012. During this time period, the attitudes of
      physicians in our department of medicine toward CAM became much more positive,
      and physicians showed an increased willingness to use CAM to address patient care
      needs. However, knowledge of and experience with many specific CAM treatments did
      not change. These results will be used to develop further educational
      interventions and research studies. 

PMID- 24439647
TI  - Butterbur extract: prophylactic treatment for childhood migraines.
AB  - The incidence of migraine headaches in childhood is increasing. Migraines are
      often difficult to diagnose in pediatrics and even more difficult to treat and
      prevent. In order to decrease the impact of the condition on the child and the
      family, prophylactic treatment is recommended if the child is experiencing
      disabling migraines. The medications currently prescribed for the prevention of
      pediatric migraines often have significant side effects and are of questionable
      therapeutic value. For those patients and parents who are interested in
      alternative therapies and natural remedies for preventive treatment of pediatric
      migraines, butterbur extract derived from the butterbur plant, Petasites
      hybridus, has emerged as a promising treatment. This paper discusses the impact
      of migraines among pediatric patients, the rationale for the preventative
      treatment of pediatric migraines, the current therapies and the relevance of
      butterbur extract as a prophylactic treatment for migraines in this patient
      population. 

PMID- 24439648
TI  - Complementary therapy provision in a London community clinic for people living
      with HIV/AIDS: a case study.
AB  - AIM: To present a case study of complementary therapy (CT) provision within a
      community HIV multi-agency service in a Northwest London deprived area. METHODS:
      Anonymised routine service data were provided for all clients (n = 1030) August
      2010 to October 2012. Face-to-face meetings provided feedback from volunteers (9
      CT-using clients and 9 staff). RESULTS: CT-users were demographically similar to
      other clients. Support for coping with HIV was commonly cited as a service
      benefit. Over 26 months 1416 CT sessions were provided; 875 aromatherapy and 471
      shiatsu. CT-users' most common concerns were pain (48%), stress (15%) and
      insomnia (13%), few had heard of or used CT before. Perceived mental and
      emotional benefits included relaxation,stress relief, relieving musculoskeletal
      aches and pains. Service challenges included time and funding, though staff felt
      CT may be cost-effective. CONCLUSIONS: CT may provide important support and
      treatment options for HIV disease, but cost effectiveness requires further
      evaluation.

PMID- 24439649
TI  - Feasibility of using whole body vibration as a means for controlling spasticity
      in post-stroke patients: a pilot study.
AB  - To examine the feasibility of adapting whole body vibration (WBV) in the
      hemiplegic legs of post-stroke patients and to investigate the anti-spastic
      effects, and the improvement of motor function and walking ability. Twenty-five
      post-stroke patients with lower-limb spasticity were enrolled in the study. Each
      subject sat with hip joint angles to approximately 90 degrees  of flexion, and
      with knee joint angles to 0 degrees  of extension. WBV was applied at 30 Hz (4-8
      mm amplitude) for 5 min on hamstrings, gastrocnemius and soleus muscles. The
      modified Ashworth scale was significantly decreased, active and passive range of
      motion (A-ROM, P-ROM) for ankle dorsiflexion and straight leg raising increased,
      and walking speed and cadence both improved during the 5-min intervention. Our
      proposed therapeutic approach could therefore be a novel neuro-rehabilitation
      strategy among patients with various severities. 

PMID- 24439650
TI  - Effect of meditation on neurophysiological changes in stress mediated depression.
AB  - Meditation is a complex mental practice involving changes in sensory perception,
      cognition, hormonal and autonomic activity. It is widely used in psychological
      and medical practices for stress management as well as stress mediated mental
      disorders like depression. A growing body of literature has shown that meditation
      has profound effects on numerous physiological systems that are involved in the
      pathophysiology of major depressive disorder (MDD). Although meditation-based
      interventions have been associated with improvement in depressive symptoms and
      prevention of relapse, the physiological mechanisms underlying the therapeutic
      effects of meditation are not clearly defined and even paradoxical. This paper
      reviews many of the physiological abnormalities found in cytokine & stress
      mediated depression and the reversal of these anomalies by different meditation
      techniques. 

PMID- 24439651
TI  - Comparison of the effects of Matricaria chamomila (Chamomile) extract and
      mefenamic acid on the intensity of premenstrual syndrome.
AB  - The study aimed to compare the effects of Chamomile Extract and Mefenamic acid
      (MA) on the intensity of Premenstrual syndrome (PMS) symptoms. This study was a
      clinical randomized double blind trial, carried out with 90 students living in
      the dorms of Iran. The participants filled the daily forms about the intensity of
      PMS for two consecutive months. Once the definitive diagnosis of PMS was made,
      the participants were divided into two groups, each receiving either Chamomile
      capsule 100 mg or MA 250 mg three times a day. Intensity reduction of emotional
      symptoms was significantly higher among Chamomile Extract-users (30.1 +/- 26.6
      and 33.4 +/- 25.3 percent) than that among MA-users (11.6 +/- 25.7 and 10.7 +/-
      26.8 percent) after two cycles intervention (p < 0.001). Intensity reduction of
      physical symptoms was not significantly different (p > 0.05) among groups.
      Consumption of Chamomile seems to be more effective than MA in relieving the
      intensity of PMS associated symptomatic psychological pains. 

PMID- 24439652
TI  - Cypriot nurses' knowledge and attitudes towards alternative medicine.
AB  - PURPOSE: To investigate Cypriot nurses' knowledge and attitude towards
      alternative treatments. METHODS: Two hundred randomly selected registered Nurses
      from public hospitals in Cyprus were administered an anonymous self-report
      questionnaire with closed-type questions. The particular questionnaire has
      previously been used in similar surveys. Six questions referred to demographic
      data and 14 questions to attitudes and knowledge towards alternative medicine.
      One hundred and thirty-eight questionnaires were adequately completed and
      evaluated. Descriptive and inferential statistics was performed. SPSS 17.0 was
      used. Statistical significance was set at p < 0.05. RESULTS: Over 1/3 of our
      sample nurses reported that they had turned to some form of alternative treatment
      at some point in their lives in order to deal with a certain medical situation.
      Most of these nurses who reported some knowledge on specific alternative
      treatment methods, (75.9%) also reported using such methods within their clinical
      practice. The nurses who had received some form of alternative treatment reported
      using them more often in their clinical practice, in comparison to those who had
      never received such treatment (Mann-Whitney U = 1137, p = 0.006). The more
      frequently nurses used alternative treatment in their clinical practice, the more
      interested they got in expanding their knowledge on the subject (Pearson's r =
      0.250, p = 0.006). CONCLUSION: Most nurses are familiar with alternative medicine
      and interested in expanding their knowledge on subject, despite the fact that
      they do not usually practice it. Special education and training as well as
      legislative actions are necessary for alternative medicine to be broadly
      accepted.

PMID- 24439653
TI  - Clinical efficacy analysis of the mouth rinsing with pomegranate and chamomile
      plant extracts in the gingival bleeding reduction.
AB  - Medicinal plants represent important therapeutic resources to health restoration,
      including the use of herbal products in the mouth conditions treatment. A
      randomized controlled clinical trial was performed in order to evaluate the
      effectiveness of mouth rinse with pomegranate and chamomile plant extracts,
      against chlorhexidine 0.12% in the gingiva bleeding condition. The mouth rinses
      with the herbal products were effective for this case, showing thus,
      antimicrobial and anti-inflammatory properties similar to that of chlorhexidine
      0.12%. 

PMID- 24439654
TI  - Non-length-dependent and length-dependent small-fiber neuropathies associated
      with tumor necrosis factor (TNF)-inhibitor therapy in patients with rheumatoid
      arthritis: expanding the spectrum of neurological disease associated with TNF
      inhibitors.
AB  - OBJECTIVE: Small-fiber neuropathy causes severe burning pain, requires diagnostic
      approaches such as skin biopsy, and encompasses two subtypes based on
      distribution of neuropathic pain. Such biopsy-proven subtypes of small-fiber
      neuropathies have not been previously described as complications of tumor
      necrosis factor (TNF)-inhibitor therapy. METHODS: We therefore characterized
      clinical and skin biopsy findings in three rheumatoid arthritis (RA) patients who
      developed small-fiber neuropathies associated with TNF-inhibitors. We also
      conducted a systematic review of the literature to characterize subtypes of
      neuropathies previously reported in association with TNF-inhibitor therapy.
      RESULTS: Two patients presented with a "non-length-dependent" small-fiber
      neuropathy, experiencing unorthodox patterns of burning pain affecting the face,
      torso, and proximal extremities. Abnormal skin biopsy findings were limited to
      the proximal thigh, which is a marker of proximal-most dorsal root ganglia
      degeneration. In contrast, one patient presented with a "length-dependent" small
      fiber neuropathy, experiencing burning pain only in the feet. Abnormal skin
      biopsy findings were limited to the distal feet, which is a marker of distal-most
      axonal degeneration. One patient developed a small-fiber neuropathy in the
      context of TNF-inhibitor-induced lupus. In all patients, neuropathies occurred
      during TNF-inhibitor-induced remission of RA disease activity and improved on
      withdrawal of TNF-inhibitors. CONCLUSIONS: We describe a spectrum of small-fiber
      neuropathies not previously reported in association with TNF-inhibitor therapy,
      with clinical and skin biopsy findings suggestive of dorsal root ganglia as well
      as axonal degeneration. The development of small-fiber neuropathies during
      inactive joint disease and improvement of neuropathic pain upon withdrawal of TNF
      inhibitor suggest a causative role of TNF-inhibitors.

PMID- 24439656
TI  - Benchmarking 30 day mortality after palliative chemotherapy for solid tumours.

PMID- 24439655
TI  - Interaction of NPSR1 genotypes and probiotics in the manifestation of atopic
      eczema in early childhood.
AB  - BACKGROUND: Neuropeptide S Receptor (NPSR1) gene has been associated with
      multiple allergic phenotypes in several patient populations. OBJECTIVE: We
      analysed the effect of the NPSR1 genotypes in the development of asthma,
      rhinitis, eczema, or food allergy in children randomly receiving either probiotic
      or placebo treatment. METHODS: 796 children born to families at high risk for
      allergic diseases were examined by a paediatrician at the age of three months,
      six months, two years, and five years. Asthma, rhinitis, eczema, and food allergy
      were diagnosed according to international guidelines. Treatment with probiotics
      (double-blinded and placebo controlled) was begun with mothers at 35 weeks of
      gestation age and continued after the birth of infants up to the age of six
      months. Association and additive inheritance models were used in genetic
      analyses. RESULTS: Distribution of the hopo546333 was suggestive in the group of
      patients with atopic eczema at two years. The hopo546333_G was found more often
      in those with eczema in the placebo group (p=0.048, after Bonferroni correction)
      and the hopo546333_A was found more often in those with eczema and probiotics
      compared to those with eczema and placebo treatment. None of the NPSR1 tagging
      SNPs was associated with asthma, IgE-mediated asthma, or sensitisation. Allergic
      disease in both parents doubled the risk for IgE-mediated allergic disease (OR
      2.1). CONCLUSIONS: The NPSR1 gene SNP hopo546333 showed a suggestive association
      for high IgE-associated atopic eczema at two years.

PMID- 24439658
TI  - AIDS: Lisson Grove, North West London, 1986.

PMID- 24439657
TI  - Improving communication in general practice when mental health issues appear:
      piloting a set of six evidence-based skills.
AB  - OBJECTIVE: To test a communication skills training program teaching general
      practitioners (GPs) a set of six evidence-based mental health related skills.
      METHODS: A training program was developed and tested in a pilot test-retest study
      with 21 GPs. Consultations were videotaped and actors used as patients. A coding
      scheme was created to assess the effect of training on GP behavior. Relevant
      utterances were categorized as examples of each of the six specified skills. The
      GPs' self-perceived learning needs and self-efficacy were measured with
      questionnaires. RESULTS: The mean number of GP utterances related to the six
      skills increased from 13.3 (SD 6.2) utterances before to 23.6 (SD 7.2) utterances
      after training; an increase of 77.4% (P<0.001). Effect sizes varied from 0.23 to
      1.37. Skills exploring emotions, cognitions and resources, and the skill Promote
      coping, increased significantly. Self-perceived learning needs and self-efficacy
      did not change significantly. CONCLUSION: The results from this pilot test are
      encouraging. GPs enhanced their use on four out of six mental health related
      communication skills significantly, and the effects were medium to large.
      PRACTICE IMPLICATIONS: This training approach appears to be an efficacious
      approach to mental health related communication skills training in general
      practice.

PMID- 24439659
TI  - Editorial overview: Cell architecture: Cellular organization and function.

PMID- 24439663
TI  - Sleep ability mediates individual differences in the vulnerability to sleep loss:
      evidence from a PER3 polymorphism.
AB  - Sleep deprivation is highly prevalent in our 24/7 society with harmful
      consequences on daytime functioning on the individual level. Genetically
      determined, trait-like vulnerability contributes to prominent inter-individual
      variability in the behavioral responses to sleep loss and adverse circadian
      phase. We aimed at investigating the effects of differential sleep pressure
      levels (high vs low) on the circadian modulation of neurobehavioral performance,
      sleepiness correlates, and nap sleep in individuals genotyped for a polymorphism
      in the clock gene PERIOD3. Fourteen homozygous long (PER3(5/5)) and 15 homozygous
      short (PER3(4/4)) allele carriers underwent both a 40-h sleep deprivation and
      multiple nap protocol under controlled laboratory conditions. We compared
      genotypes regarding subjective and ocular correlates of sleepiness, unintentional
      sleep episodes as well as psychomotor vigilance during both protocols. Nap sleep
      was monitored by polysomnography and visually scored according to standard
      criteria. The detrimental effects of high sleep pressure on sleepiness correlates
      and psychomotor vigilance were more pronounced in PER3(5/5) than PER3(4/4)
      carriers. Under low sleep pressure, both groups showed similar circadian time
      courses. Concomitantly, nap sleep efficiency and subjective sleep quality across
      all naps tended to be higher in the more vulnerable PER3(5/5) carriers. In
      addition, PER3-dependent sleep-loss-related attentional lapses were mediated by
      sleep efficiency across the circadian cycle. Our data corroborate a greater
      detrimental impact of sleep deprivation in PER3(5/5) compared to PER3(4/4)
      carriers. They further suggest that the group with greater attentional
      performance impairment due to sleep deprivation (PER3(5/5) carriers) is superior
      at initiating sleep over the 24-h cycle. This higher sleep ability may mirror a
      faster sleep pressure build-up between the multiple sleep opportunities and thus
      a greater flexibility in sleep initiation. Finally, our data show that this
      higher nap sleep efficiency is positively related to attentional failures under
      sleep loss conditions and might thus be used as a marker for inter-individual
      vulnerability to elevated sleep pressure. 

PMID- 24439664
TI  - Limbic systems for emotion and for memory, but no single limbic system.
AB  - The concept of a (single) limbic system is shown to be outmoded. Instead,
      anatomical, neurophysiological, functional neuroimaging, and neuropsychological
      evidence is described that anterior limbic and related structures including the
      orbitofrontal cortex and amygdala are involved in emotion, reward valuation, and
      reward-related decision-making (but not memory), with the value representations
      transmitted to the anterior cingulate cortex for action-outcome learning. In this
      'emotion limbic system' a computational principle is that feedforward pattern
      association networks learn associations from visual, olfactory and auditory
      stimuli, to primary reinforcers such as taste, touch, and pain. In primates
      including humans this learning can be very rapid and rule-based, with the
      orbitofrontal cortex overshadowing the amygdala in this learning important for
      social and emotional behaviour. Complementary evidence is described showing that
      the hippocampus and limbic structures to which it is connected including the
      posterior cingulate cortex and the fornix-mammillary body-anterior thalamus
      posterior cingulate circuit are involved in episodic or event memory, but not
      emotion. This 'hippocampal system' receives information from neocortical areas
      about spatial location, and objects, and can rapidly associate this information
      together by the different computational principle of autoassociation in the CA3
      region of the hippocampus involving feedback. The system can later recall the
      whole of this information in the CA3 region from any component, a feedback
      process, and can recall the information back to neocortical areas, again a
      feedback (to neocortex) recall process. Emotion can enter this memory system from
      the orbitofrontal cortex etc., and be recalled back to the orbitofrontal cortex
      etc. during memory recall, but the emotional and hippocampal networks or 'limbic
      systems' operate by different computational principles, and operate independently
      of each other except insofar as an emotional state or reward value attribute may
      be part of an episodic memory. 

PMID- 24439665
TI  - Filicide-suicide ideation among Taiwanese parents with school-aged children:
      prevalence and associated factors.
AB  - This study explored the prevalence of filicide-suicide ideation among Taiwanese
      parents with school-aged children. Multiple risk factors associated with filicide
      suicide ideation were assessed, and the potential effect of traditional family
      values was evaluated. A random sample of 1,564 parents was recruited from 21
      elementary schools in a rural area of Taiwan. Potential risk factors, including
      demographics, family finance, psychological maladjustment, family interaction,
      and cultural beliefs, were further examined using a hierarchical logistic
      regression. Overall, 14.6% of the respondents reported having filicide-suicide
      ideation during the past year. The hierarchical logistic regression analysis
      showed that demographic factors including age, gender, and ethnicity had no
      significant effect. Family finances, depression, and conflict with the
      respondent's spouse were positively associated with filicide-suicide ideation.
      Finally, the parents' beliefs in traditional family values had a positive effect
      on filicide-suicide ideation. In other words, filicide-suicide thoughts were more
      common among those who upheld a strong parental responsibility for care giving
      and family solidarity. This study revealed a substantial prevalence of filicide
      suicide ideation among local parents and identified a number of risk factors
      associated with those thoughts, namely family financial status, parental
      depression, and conflict with one's spouse. More importantly, the results
      highlighted the effect of traditional family values in the process. The potential
      intention of filicide-suicide as mercy killing and its cultural relevance were
      discussed. 

PMID- 24439666
TI  - [Economic crisis and social vulnerability in older people].

PMID- 24439667
TI  - The making of expert clinicians: reflective practice.
AB  - Debriefing is a rigorous reflection process which helps trainees recognize and
      resolve clinical and behavioral dilemmas raised by a clinical case. This approach
      emphasizes eliciting trainees'assumptions about the situation and their reasons
      for performing as they did (mental models). It analyses their impact on actions,
      to understand if it is necessary to maintain them or construct new ones that may
      lead to better performance in the future. It blends evidence and theory from
      education research, the social and cognitive sciences, and experience drawn from
      conducting and teaching debriefing to clinicians worldwide, on how to improve
      professional effectiveness through "reflective practice". 

PMID- 24439668
TI  - [Chromoblastomycosis].

PMID- 24439669
TI  - [Bilateral subdural hematoma after diagnostic lumbar puncture].

PMID- 24439670
TI  - Increased expression of oxidative enzymes in adipose tissue following PPARalpha
      activation.
AB  - OBJECTIVE: Evaluate the effect of fenofibrate treatment on the expression of
      PPARalpha and oxidative enzymes in adipose tissue. MATERIALS/METHODS: Wistar male
      rats were fed a balanced diet supplemented with 100mg.Kg-1 bw.day-1 fenofibrate
      (Sigma) during nine days. Plasma glucose, free fatty acids (FFA) leptin and
      insulin were determined. PPARalpha, ACO and CPT-1 mRNA expression and amount of
      PPARalpha and PPARgamma protein were assessed in epididymal adipose tissue. Oral
      glucose tolerance test was evaluated into overnight fasted rats. Glucose uptake
      was measured in adipocytes isolated from epididymal fat pads in the presence or
      absence of insulin (25ng/mL). RESULTS: Fenofibrate treatment increased PPARalpha
      and PPARgamma protein abundance in adipose tissue. In addition to it well- known
      effect on oxidative enzymes in liver, fenofibrate treatment also induces a high
      expression of Acyl CoA Oxidase (ACO) and Carnitine palmitoyltransferase 1 (CPT-1)
      in adipose tissue. Furthermore, we have shown that the fenofibrate treatment
      improves the glucose tolerance and enhance the glucose uptake by adipocytes.
      CONCLUSION: Altogether, the data suggest that fenofibrate have a direct effect in
      adipose tissue contributing to the low adiposity and improvement of glucose
      homeostasis.

PMID- 24439671
TI  - Regulation and expression of aberrant methylation on irinotecan metabolic genes
      CES2, UGT1A1 and GUSB in the in-vitro cultured colorectal cancer cells.
AB  - OBJECTIVE: To evaluate the aberrant methylation gene expression related to the
      irinotecan (CPT-11) metabolic enzymes in different colorectal cancer cell
      strains; provide new thoughts and measures for reverse of tumor drug resistance.
      METHODS: Studied the aberrant methylation state of CES2, UGT1A1 and GUSB in eight
      colorectal cancer cell strains through MSP method; and analyze the expression of
      the target gene after being dealt with DAC. RESULTS: UGT1A1 showed methylation in
      five cell strains, while CES2 and GUSB respectively showed consistent
      unmethylation or hemimethylation. After being dealt with DAC, CES2 and GUSB mRNA
      showed different expressions but not significant. The expression quantity of
      UGT1A1mRNA in the low-expression cell strains increased significantly. The
      expression of UGT1A1 protein where POSITIVE presented low expression was up
      regulated to different degrees. Negative tropism was found in CES2 and UGT1A1.
      CONCLUSION: Methylation in UGT1A1 gene expression silencing as an important
      mechanism; methylation could provide an effective target for methylation
      regulation intervening in the treatment of CPT-11. Meanwhile, studies found that
      the changes in expressions of CES2 and GUSB might be resulted from some unknown
      target that still existed during the regulation, or from the influence of
      methylation in the non-core zone of promoters on the gene transcription.

PMID- 24439672
TI  - Expression and clinical significance of tyrosine phosphatase SHP-2 in colon
      cancer.
AB  - Protein-tyrosine phosphatase SHP-2, encoded by gene PTPN11, has been identified
      as a tumor-promoting factor in several types of leukemia and is hyper-activated
      by other mechanisms in some solid tumors including gastric cancer, breast cancer,
      non-small cell lung cancer (NSCLC), etc. But few were reported on the expression
      and significances of SHP-2 in colon cancer. Here, we detect SHP-2 expression in
      colon cancer cells, colon cancer-induced by AOM+DSS in mice and 232 human colon
      cancer specimens, including 58 groups of self-matched adjacent peritumor tissues
      and normal tissues. We found that compared to the normal colon tissues, SHP-2
      significantly decreased in tumor tissues (P<0.001). The same results were got in
      colon tumor cells as well as mice colon tumors. And in humans samples, low SHP-2
      expression showed a significantly correlation with poor tumor differentiation
      (P<0.05), late TNM stage (P=0.1666) and lymph node metastasis (P<0.05). 

PMID- 24439673
TI  - Reconsidering racial/ethnic differences in sterilization in the United States.
AB  - OBJECTIVE: Cross-sectional studies have found that low-income and racial/ethnic
      minority women are more likely to use female sterilization and less likely to
      rely on a partner's vasectomy than women with higher incomes and whites. However,
      studies of pregnant and postpartum women report that racial/ethnic minorities,
      particularly low-income minority women, face greater barriers in obtaining a
      sterilization than do whites and those with higher incomes. In this paper, we
      address this apparent contradiction by examining the likelihood a woman gets a
      sterilization following each delivery, which removes from the comparison any
      difference in the number of births she has experienced. STUDY DESIGN: Using the
      2006-2010 National Survey of Family Growth, we fit multivariable-adjusted
      logistic and Cox regression models to estimate odds ratios and hazard ratios for
      getting a postpartum or interval sterilization, respectively, according to
      race/ethnicity and insurance status. RESULTS: Women's chances of obtaining a
      sterilization varied by both race/ethnicity and insurance. Among women with
      Medicaid, whites were more likely to use female sterilization than African
      Americans and Latinas. Privately insured whites were more likely to rely on
      vasectomy than African Americans and Latinas, but among women with Medicaid-paid
      deliveries reliance on vasectomy was low for all racial/ethnic groups.
      CONCLUSIONS: Low-income racial/ethnic minority women are less likely to undergo
      sterilization following delivery compared to low-income whites and privately
      insured women of similar parities. This could result from unique barriers to
      obtaining permanent contraception and could expose women to the risk of future
      unintended pregnancies. IMPLICATIONS: Low-income minorities are less likely to
      undergo sterilization than low-income whites and privately insured minorities,
      which may result from barriers to obtaining permanent contraception, and exposes
      women to unintended pregnancies.

PMID- 24439674
TI  - Effectiveness, safety and acceptability of Sino-implant (II) during the first
      year of use: results from Kenya and Pakistan.
AB  - BACKGROUND: Sino-implant (II) is a two-rod subcutaneous contraceptive implant
      used up to 4 years, containing 150 mg of levonorgestrel. We conducted two
      observational studies of Sino-implant (II) to evaluate its performance in routine
      service delivery settings. METHODS: We enrolled 1326 women age 18-44 who had Sino
      implant (II) inserted at clinics in Pakistan and Kenya. Women were followed-up
      using either an active or passive follow-up scheme in each study. Study outcomes
      were: one-year cumulative pregnancy and discontinuation rates; rates of insertion
      and removal complications; adverse event and side effect rates; reasons for
      discontinuation; and implant acceptability and satisfaction with clinic services.
      RESULTS: A total of 754 women returned for at least one follow-up visit. The
      overall Pearl pregnancy rate was 0.4 per 100 woman-years [95% confidence interval
      (CI) 0.1, 0.9] resulting from 1 confirmed post-insertion pregnancy in Kenya and 4
      in Pakistan. Country-specific Pearl rates were 0.2 (95% CI 0.0, 0.9) in Kenya and
      0.6 (95% CI 0.2, 1.6) in Pakistan. The total cumulative 12-month probability of
      removal was 7.6% (95% CI 6.1, 9.1), with country-specific removal probabilities
      of 3.7% in Kenya (95% CI 2.1, 5.3) and 10.8% in Pakistan (95% CI 8.5, 13.2). Four
      serious adverse events occurred in Kenya and none occurred in Pakistan; one SAE
      (an ectopic pregnancy) was possibly related to Sino-implant (II). Most women in
      both countries said they would recommend the implant to others. CONCLUSION: The
      results from these studies reveal high effectiveness and favorable safety and
      acceptability during the first year of use of Sino-implant. IMPLICATION: The
      favorable Sino-implant (II) findings from Kenya and Pakistan provide further
      evidence from disparate regions that Sino-implant (II) is safe, effective and
      acceptable during routine service delivery.

PMID- 24439675
TI  - Comparative study on mannose 6-phosphate residue contents of recombinant
      lysosomal enzymes.
AB  - As most recombinant lysosomal enzymes are incorporated into cells via mannose 6
      phosphate (M6P) receptors, the M6P content is important for effective enzyme
      replacement therapy (ERT) for lysosomal diseases. However, there have been no
      comprehensive reports of the M6P contents of lysosomal enzymes. We developed an
      M6P assay method comprising three steps, i.e., acid hydrolysis of glycoproteins,
      derivatization of M6P, and high-performance liquid chromatography, and determined
      the M6P contents of six recombinant lysosomal enzymes now available for ERT and
      one in the process of development. The assay is easy, specific, and reproducible.
      The results of the comparative study revealed that the M6P contents of agalsidase
      alfa, agalsidase beta, modified alpha-N-acetylgalactosaminidase, alglucosidase
      alfa, laronidase, idursulfase, and imiglucerase are 2.1, 2.9, 5.9, 0.7, 2.5, 3.2,
      and <0.3 mol/mol enzyme, respectively. The results were correlated with those of
      the biochemical analyses previously performed and that of the binding assay of
      exposed M6P of the enzymes with the domain 9 of the cation-independent M6P
      receptor. This assay method is useful for comparison of the M6P contents of
      recombinant lysosomal enzymes for ERT.

PMID- 24439676
TI  - Clinical evidence for a link between microparticle-associated tissue factor
      activity and overt disseminated intravascular coagulation in patients with acute
      myelocytic leukemia.

PMID- 24439677
TI  - Role of paraoxonase-1 in CYP2C19 loss-of-function carriers.

PMID- 24439678
TI  - A higher d-dimer threshold safely rules-out pulmonary embolism in very elderly
      emergency department patients.
AB  - INTRODUCTION: D-dimer is commonly used in the workup of suspected Pulmonary
      Embolism (PE), but its specificity decreases with age. We evaluated whether using
      a higher cutoff value for D-dimer could increase the test specificity without
      reducing its sensitivity for ruling-out PE in elderly and very elderly patients
      presenting to the Emergency Department (ED). MATERIAL AND METHODS: All patients
      with D-dimer and pulmonary Computed Tomography Angiography (CTA) performed in the
      ED of Vimercate Hospital, from 2010 through 2012 for clinical suspicion of PE
      were included in this retrospective cohort study. RESULTS: Study population 481
      patients (63.4% women, mean age 73.0 +/- 16.1 years, confirmed PE 22.5%). In very
      elderly patients (aged 80 or more years, n=191), compared with standard 490 ng/mL
      D-dimer threshold, both higher fixed (1000 ng/mL) and age-adjusted cutoffs
      increase the specificity of D-dimer for the exclusion of PE maintaining a
      Negative Predictive Value of 100%. Potentially avoided CTAs were 12(6.3%) using
      1000 ng/mL cutoff and 10(5.2%) age-adjusted. In very elderly patients the Number
      Needed to Test was incalculable for the standard cutoff (0 cases), 16 for 1000
      ng/mL and 19 for age-adjusted. In patients with PE, index episode mortality was
      6.5%, and death occurred only in subjects with D-dimer values above 1000ng/mL and
      age-adjusted thresholds. CONCLUSION: For very elderly patients with suspected PE
      in ED, both higher fixed D-dimer (1000 ng/mL) and age-adjusted thresholds
      increase test specificity for excluding PE without reducing its sensitivity,
      leading to a safe reduction in the number of CTAs.

PMID- 24439679
TI  - Procoagulant activity and cellular origin of microparticles in human amniotic
      fluid.
AB  - INTRODUCTION: Amniotic fluid contains various procoagulant factors involved in
      intro-vascular amniotic fluid-induced coagulopathies. During the progression of
      normal pregnancy, microparticles would be shed off from cells and accumulate in
      amniotic fluid over time. In this study, our aims were to investigate the
      cellular origin and procoagulant entity of these microparticles. MATERIALS AND
      METHODS: Twenty amniotic fluid samples from healthy parturient women were
      collected, and the microparticles were isolated and stained with phycoerythrin
      labeled antibodies to CD138, CD41a, CD144 and CD11b to identify their cellular
      origin. Their phosphatidylserine and tissue factor expression levels were
      quantified with fluorescein isothiocyanate-labeled annexin V and anti-tissue
      factor antibody staining. Their procoagulant activity was tested with plasma
      coagulation assay and factor Xase and prothrombinase assays. RESULTS: Phenotypic
      analysis showed 36.8% and 33.8% of amniotic fluid microparticles positive for
      CD138 and CD11b, respectively, indicating their epithelial cell or leukocyte
      origin. Of these microparticles, 66.3+/-5.9% expressed phosphatidylserine while
      37.4+/-4.1% expressed tissue factor. In addition, amniotic fluid microparticles
      could significantly shorten the plasma coagulation time and increase the
      production of factor Xa and thrombin. Inhibition assays with annexin V and anti
      tissue factor antibody confirmed the coagulation effects of amniotic fluid
      microparticles. CONCLUSION: The microparticles derived from epithelial and
      leukocytes may be a mechanism of amniotic fluid-induced coagulopathies.

PMID- 24439681
TI  - Therapeutic potential of Na(V)1.1 activators.
AB  - Sodium channel inhibitors have been developed and approved as drugs to treat a
      variety of indications. By contrast, sodium channel activators have not
      previously been considered relevant in a therapeutic setting owing to their high
      risk of toxicity and side effects. Here we present an opinion that selective
      activators of the Na(V)1.1 sodium channel may hold therapeutic potential for
      diseases such as epilepsy, schizophrenia, and Alzheimer's disease. Central to
      this novel avenue of sodium channel drug discovery is that fact that Na(V)1.1
      comprises the majority of the sodium current in specific inhibitory interneurons.
      Conversely, it plays only a modest role in excitatory neurons owing to the high
      redundancy of other types of sodium channels in these cells. We discuss the
      biological background and rationale and present reflections on how to identify
      activators of Na(V)1.1.

PMID- 24439682
TI  - Health related quality of life changes in somatising patients after individual
      versus group cognitive behavioural therapy: a randomized clinical trial.
AB  - OBJECTIVE: To assess changes in health related quality of life after a cognitive
      behavioural program for patients diagnosed with abridged somatization disorder in
      primary care. METHOD: A multicentre, randomized, parallel group, controlled trial
      was designed. 168 patients were recruited from 29 primary health care centres in
      Spain and were randomly assigned to one of the three study arms: treatment as
      usual improved with Smith's norms, individual cognitive behavioural treatment,
      and group cognitive behavioural treatment. Health-related quality of life was
      assessed using SF-36 Health Survey. RESULTS: Individual cognitive behavioural
      treatment achieves greater changes in health related quality of life than group
      cognitive behavioural therapy and treatment as usual. Improvement in health
      related quality of life was fully observed at 12 month, and partially at 6
      months. The modality of intervention interacts with time in all dimensions except
      for Physical functioning and Vitality. Patients who received individual cognitive
      behavioural therapy treatment had better scores in Physical and Mental health
      summary measures at 12 month follow-up. CONCLUSIONS: Individual cognitive
      behavioural treatment is the most effective way to improve health related quality
      of life in abridged somatization disorder patients, and its effects are sustained
      over time. Also, regardless of the type of intervention, physical functioning
      improves compared with treatment as usual.

PMID- 24439680
TI  - Small molecule SIRT1 activators for the treatment of aging and age-related
      diseases.
AB  - Recent studies in mice have identified single molecules that can delay multiple
      diseases of aging and extend lifespan. In theory, such molecules could prevent
      dozens of diseases simultaneously, potentially extending healthy years of life.
      In this review, we discuss recent advances, controversies, opportunities, and
      challenges surrounding the development of SIRT1 activators, molecules with the
      potential to delay aging and age-related diseases. Sirtuins comprise a family of
      NAD+-dependent deacylases that are central to the body's response to diet and
      exercise. New studies indicate that both natural and synthetic sirtuin activating
      compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin
      activity, thereby conferring broad health benefits in rodents, primates, and
      possibly humans. The fact that two-thirds of people in the USA who consume
      multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores
      the importance of understanding the biochemical mechanism, physiological effects,
      and safety of STACs.

PMID- 24439683
TI  - Struggling in an emotional avoidance culture: a qualitative study of stress as a
      predisposing factor for somatoform disorders.
AB  - OBJECTIVE: To explore patterns of experienced stress and stress reactions before
      the onset of illness in the life history of patients with severe somatoform
      disorders to identify predisposing stress-mechanisms. METHODS: A systematic,
      thematic analysis was conducted on data collected from 24 semi-structured
      individual life history interviews. RESULTS: Generally, patients had experienced
      high psychosocial stress during childhood/youth. However, there was considerable
      variability. Characteristic of all patients were narrations of how communication
      with significant adults about problems, concerns, and emotions related to stress
      were experienced to be difficult. The patients described how this involved
      conflicts stemming from perceived absent, insufficient, or dismissive
      communication during interactions with significant adults. We conceptualized this
      empirically based core theme as "emotional avoidance culture." Further, three
      related subthemes were identified: Generally, patients 1.) experienced
      difficulties communicating problems, concerns, and related complex feelings in
      close social relations; 2.) adapted their emotional reactions and communication
      to an emotional avoidance culture, suppressing their needs, vulnerability and
      feelings of sadness and anger that were not recognized by significant adults; and
      3.) disconnected their stress reaction awareness from stressful bodily sensations
      by using avoidant behaviors e.g. by being highly active. CONCLUSION: Patients
      adapted to an emotional avoidance culture characterized by difficult and
      conflicting communication of concerns and related emotions in social interactions
      with significant adults. Patients experienced low ability to identify and express
      stress-related cognitions, emotions and feelings, and low bodily and emotional
      self-contact, which made them vulnerable to stressors. Generally, patients
      resolved stress by avoidant behaviors, prolonging their stress experience.

PMID- 24439684
TI  - Longing for existential recognition: a qualitative study of everyday concerns for
      people with somatoform disorders.
AB  - OBJECTIVE: Patients with somatoform disorders could be vulnerable to stressors
      and have difficulties coping with stress. The aim was to explore what the
      patients experience as stressful and how they resolve stress in everyday life.
      METHODS: A cross-sectional retrospective design using 24 semi-structured
      individual life history interviews. Data-analysis was based on grounded theory.
      RESULTS: A major concern in patients was a longing for existential recognition.
      This influenced the patients' self-confidence, stress appraisals, symptom
      perceptions, and coping attitudes. Generally, patients had difficulties with self
      confidence and self-recognition of bodily sensations, feelings, vulnerability,
      and needs, which negatively framed their attempts to obtain recognition in social
      interactions. Experiences of recognition appeared in three different modalities:
      1) "existential misrecognition" covered the experience of being met with distrust
      and disrespect, 2) "uncertain existential recognition" covered experiences of
      unclear communication and a perception of not being totally recognized, and 3)
      "successful existential recognition" covered experiences of total respect and
      understanding. "Misrecognition" and "uncertain recognition" related to decreased
      self-confidence, avoidant coping behaviours, increased stress, and symptom
      appraisal; whereas "successful recognition" related to higher self-confidence,
      active coping behaviours, decreased stress, and symptom appraisal. CONCLUSION:
      Different modalities of existential recognition influenced self-identity and
      social identity affecting patients' daily stress and symptom appraisals, self
      confidence, self-recognition, and coping attitudes. Clinically it seems crucial
      to improve the patients' ability to communicate concerns, feelings, and needs in
      social interactions. Better communicative skills and more active coping could
      reduce the harm the patients experienced by not being recognized and increase the
      healing potential of successful recognition.

PMID- 24439685
TI  - Anxiety and depression predicted by medically unexplained symptoms in Pakistani
      children: a case-control study.
AB  - OBJECTIVE: To explore association between medically unexplained symptoms in
      children in Pakistan with emotional difficulties and functional impairments.
      METHODS: We conducted a matched three-group case-control study of 186 children
      aged 8-16 years in Lahore, Pakistan. Cases were 62 children with chronic somatic
      symptoms for which no organic cause was identified after investigations. Two
      control groups of 62 children with chronic medical paediatric conditions, and 62
      healthy children were identified. Cases and controls were matched for gender,
      age, and school class. Somatisation was measured with the Children's Somatisation
      Inventory (CSI-24) while anxiety and depression were measured with the Spencer
      Children's Anxiety Scale and the Short Mood and Feelings Questionnaire
      respectively. All questionnaires were translated into Urdu. RESULTS: Mean age was
      11.7 years (SD=2.1). Cases scored significantly higher on somatisation (CSI-24),
      anxiety and depression than both control groups. Paediatric controls scored
      significantly higher than healthy controls on all three measures. Two
      hierarchical linear regression models were used to explore if somatisation
      predicted depression and anxiety while controlling for several confounders.
      Somatisation (higher CSI-24 scores) independently and significantly predicted
      higher anxiety (beta=.37, p=.0001) and depression (beta=.41, p=.0001) scores.
      CONCLUSION: This is the first study to show an association between medically
      unexplained symptoms and anxiety and depression in Pakistani children. This
      highlights the importance of screening for emotional difficulties in children
      presenting with unexplained somatic symptoms in this region.

PMID- 24439686
TI  - Does attachment anxiety increase vulnerability to headache?
AB  - BACKGROUND: Attachment-related anxiety and avoidance are potentially important
      aspects of pain experience and management, but have not been investigated in
      episodic headache sufferers or in relation to experimentally-evoked headache.
      OBJECTIVE: To determine whether adult insecure attachment styles were associated
      with sensitivity to pain or headache before, during or after stressful mental
      arithmetic in an episodic migraine or tension-type headache (T-TH) sample.
      METHODS: Thirty-eight participants with episodic migraine, 28 with episodic T-TH
      and 20 headache-free participants intermittently received a mild electric shock
      to the forehead before, during and after stressful mental arithmetic. RESULTS: A
      preoccupied attachment style and attachment anxiety, but not attachment
      avoidance, were associated with forehead pain and the intensity of headache
      before and after, but not during stressful mental arithmetic. These relationships
      were independent of Five Factor Model personality traits. Neither attachment
      anxiety nor avoidance was associated with episodic migraine or T-TH. CONCLUSIONS:
      Anxiously attached individuals may express greater pain or show a stronger
      attentional bias toward painful sensations than securely attached individuals.
      However, distraction during psychological stress may override this attentional
      bias.

PMID- 24439687
TI  - Effectiveness of a psychosomatic day hospital treatment for the elderly: a
      naturalistic longitudinal study with waiting time before treatment as control
      condition.
AB  - OBJECTIVE: In 2006 the psychosomatic day hospital for the treatment of acute
      mental illness of elderly people opened as the first clinic of its kind in
      Germany. The aim of this study was to determine treatment effectiveness and
      identify possible effects on health care utilization. METHODS: Designed as a
      naturalistic study with waiting time before admission as a control condition, the
      primary outcome was the level of depressive symptoms as measured by the hospital
      anxiety and depression scale. Secondary outcomes were depressive and somatoform
      symptoms and syndromes as measured with the patient health questionnaire, patient
      perception of interpersonal problems and health care use before and after
      treatment. RESULTS: After treatment significant improvement (p<0.01) with
      moderate effect sizes (ES) was found in all variables from admission to discharge
      (ES from 0.3 to 0.8) and also to follow-up (ES from 0.2 to 0.6). Improvement
      remained stable at follow-up. Furthermore, after psychosomatic treatment a
      reduction in medical service usage was visible. Number of consultations (pre: 13,
      post: 9), number and length of hospital stays (pre: 1, 7 weeks, post: 0, 3 weeks)
      were both significantly (p<0.001) reduced six months after treatment as compared
      to the period six months prior to treatment. CONCLUSION: Results indicate that
      the psychosomatic day hospital treatment of the elderly is successful. Reduced
      usage of health care and the lower costs for day hospital treatment compared to
      inpatient treatment point to a positive cost-effect-ratio. Expanding this
      psychosomatic intervention would be useful in reducing the current gap in mental
      health care for the elderly.

PMID- 24439688
TI  - The association of personality trait on treatment outcomes in patients with
      chronic prostatitis/chronic pelvic pain syndrome: an exploratory study.
AB  - OBJECTIVE: This study investigated the association of personality traits with the
      baseline clinical characteristics and treatment outcomes of patients with chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Subjects were
      evaluated at baseline and at week 12 following routine treatment for CP/CPPS
      using the Korean version of the National Institutes of Health Chronic Prostatitis
      Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS; the Korean version
      of the Patient Health Questionnaire-9 (PHQ-9) to assess depression; the Korean
      version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatization;
      and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D),
      specifically the EQ-5D utility index and the EQ-5D visual analog scale (EQ-5D
      VAS), to assess quality of life (QoL). Personality traits including extraversion,
      agreeableness, conscientiousness, neuroticism, and openness were determined at
      baseline using the 44-item Big Five Inventory (BFI). The influence of personality
      traits on the clinical characteristics and treatment outcomes of patients with
      CP/CPPS was assessed using relevant statistical analyses. RESULTS: Neuroticism
      was associated with a significantly poorer treatment response and higher levels
      of depression and somatization. Extraversion, agreeableness, and
      conscientiousness had some influence on clinical characteristics but openness did
      not affect overall symptoms or the treatment response in patients with CP/CPPS.
      CONCLUSIONS: We found that neuroticism may be the most important personality
      trait associated with treatment response and the severity of depression and
      somatization in patients with CP/CPPS. However, our exploratory findings should
      be confirmed by additional studies with adequate power and improved designs.

PMID- 24439689
TI  - Medication beliefs, treatment complexity, and non-adherence to different drug
      classes in patients with type 2 diabetes.
AB  - OBJECTIVE: To assess the relationship of patients' medication beliefs and
      treatment complexity with unintentional and intentional non-adherence for three
      therapeutic groups commonly used by patients with type 2 diabetes. METHODS:
      Survey data about adherence (Medication Adherence Report Scale) and beliefs about
      medicines (Beliefs about Medicines Questionnaire) were combined with prescription
      data from the Groningen Initiative to ANalyse Type 2 diabetes Treatment (GIANTT)
      database. Patients were classified as being adherent, mainly unintentional non
      adherent, or partly intentional non-adherent per therapeutic group (glucose-,
      blood pressure-, and lipid-lowering drugs). Treatment complexity was measured
      using the Medication Regimen Complexity Index, which includes the dosage form,
      dosing frequency and additional directions of taking the drug. Analyses were
      performed using Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: Of 257
      contacted patients, 133 (52%) returned the questionnaire. The patients had a mean
      age of 66years and 50% were females. Necessity beliefs were not significantly
      different between the adherers, mainly unintentional non-adherers, and partly
      intentional non-adherers (differences smaller than 5 points on a scale from 5 to
      25). For blood pressure-lowering drugs, patients reporting intentional non
      adherence had higher concern beliefs than adherers (8 point difference, P=0.01).
      Treatment complexity scores were lower for adherers but similar for mainly
      unintentional and partly intentional non-adherers to glucose- and blood pressure
      lowering drugs. CONCLUSION: Treatment complexity was related to non-adherence in
      general. Beliefs about necessity were not strongly associated with non-adherence,
      while patients' concern beliefs may be associated with intentional non-adherence.
      However, the role of these determinants differs per therapeutic group.

PMID- 24439690
TI  - Personality and self-esteem in emerging adults with Type 1 diabetes.
AB  - OBJECTIVE: The present study examined (1) mean-level differences in self-esteem
      and Big Five personality traits between individuals with and without diabetes;
      and (2) demographic, clinical, and psychological correlates of patients' self
      esteem and Big Five. RESEARCH DESIGN AND METHODS: A total of 478 emerging adults
      with Type 1 diabetes (18-35 years old) were selected from the Belgian Diabetes
      Registry and completed questionnaires on personality, self-esteem, and diabetes
      related distress. The control group consisted of 341 healthy participants who
      were matched (1:1) on sex and age with the patient group. RESULTS: First, mean
      level differences between patients and controls differed according to patients'
      sex and illness duration. Women with diabetes reported lower self-esteem and were
      less extraverted and emotionally stable as compared to female controls. In
      contrast, men with diabetes reported higher self-esteem and were more agreeable
      but less emotionally stable as compared to male controls. Furthermore, whereas
      both patients with shorter and longer illness duration were less extraverted and
      emotionally stable as compared to controls, only patients with longer illness
      duration reported heightened agreeableness. Second, self-esteem and Big Five were
      found to relate to patients' sex and (to a lesser extent) age and illness
      duration. Finally, patients reporting elevated diabetes-related distress reported
      lower self-esteem, and were less agreeable and emotionally stable as compared to
      patients not reporting such distress. CONCLUSIONS: Patients' personality and self
      esteem might be important targets for future prevention and intervention efforts.
      The present findings can assist healthcare professionals in identifying those
      patients who might benefit the most from such programs.

PMID- 24439691
TI  - Illness perceptions predict exercise capacity and psychological well-being after
      pulmonary rehabilitation in COPD patients.
AB  - OBJECTIVE: Patients' beliefs about their disease have been associated with
      emotional adjustment and outcomes in several severe illnesses. The aim of the
      present study was to investigate whether illness perceptions before pulmonary
      rehabilitation influence exercise capacity and quality of life after
      rehabilitation in patients suffering from chronic obstructive pulmonary disease
      (COPD). METHODS: Ninety-six patients with COPD (GOLD III/IV) were approached on
      admission to rehabilitation and reassessed before discharge. Assessment included
      medical measures of FEV% predicted, and exercise capacity (6 min walk test).
      Additionally, depressive symptoms (Hospital Anxiety and Depression scale),
      anxiety (COPD specific anxiety questionnaire) and quality of life (Short Form 36
      health survey (SF-36)) were assessed. Illness beliefs were measured by the
      Revised Illness Perception Questionnaire (IPQ-R). RESULTS: Exercise capacity and
      psychological well-being (SF-36) of patients improved after rehabilitation
      programme, while physical functioning (SF-36) did not change. Additionally,
      patients showed significantly lower levels of depressive symptoms, COPD specific
      anxiety and negative perceptions of their illness after pulmonary rehabilitation
      compared to baseline. In the hierarchical multiple regression analyses, after
      controlling for socio-demographic data, psychological variables, illness severity
      and baseline scores of the corresponding variables, it was shown that illness
      perceptions before rehabilitation predicted exercise capacity and psychological
      well-being, both assessed at the end of treatment. CONCLUSION: COPD patients'
      perceptions about their illness before rehabilitation influence exercise capacity
      and quality of life (psychological well-being) after treatment. Therefore it
      might be relevant to identify and change maladaptive illness perceptions in order
      to improve medical and psychological outcome in COPD.

PMID- 24439692
TI  - The factor structure of the metabolic syndrome in obese individuals with binge
      eating disorder.
AB  - OBJECTIVE: Metabolic syndrome (MetS) is strongly linked with cardiovascular
      disease and type-II diabetes, but there has been debate over which metabolic
      measures constitute MetS. Obese individuals with binge eating disorder (BED) are
      one of the high risk populations for developing MetS due to their excess weight
      and maladaptive eating patterns, yet, the clustering patterns of metabolic
      measures have not been examined in this patient group. METHODS: 347 adults (71.8%
      women) were recruited for treatment studies for obese individuals with BED. We
      used the VARCLUS procedure in the Statistical Analysis System (SAS) to
      investigate the clustering pattern of metabolic risk measures. RESULTS: The
      analysis yielded four factors: obesity (body-mass-index [BMI] and waist
      circumference), lipids (HDL and triglycerides), blood pressure (systolic and
      diastolic blood pressure), and glucose regulation (fasting serum glucose and
      Hb1Ac). The four factors accounted for 84% of the total variances, and variances
      explained by each factor were not substantially different. There was no inter
      correlation between the four factors. Subgroup analyses by sex and by race
      (Caucasian vs. African American) yielded the same four-factor structure.
      CONCLUSION: The factor structure of MetS in obese individuals with BED is not
      different from those found in normative population studies. This factor structure
      may be applicable to the diverse population.

PMID- 24439693
TI  - Restless legs symptoms in adolescents: epidemiology, heritability, and pubertal
      effects.
AB  - AIMS: We aimed to determine the prevalence, pubertal effect, familial
      aggregation, and heritability of restless legs (RLS) symptoms in Chinese
      adolescents. In addition, the correlates and consequences of RLS symptoms were
      examined. METHODS: This was a population-based family study that involved 1549
      adolescents (probands), their parents and siblings. RLS symptoms were assessed by
      a single question measuring the core features of RLS. Subjects with RLS symptoms
      for at least once per week were considered as abnormal. Impairment of daytime
      functions, behavioral problems, health status, and lifestyle practice were also
      documented. RESULTS: The prevalence of RLS symptoms was 2.8% in adolescents and
      7.4% in their parents with female preponderance. Gender difference of RLS
      symptoms emerged in mid-pubertal adolescents (Tanner stage 3 or above). RLS
      symptoms were closely associated with various sleep problems (range of ORs=2.24
      to 32.5, p<0.05), except habitual snoring. They were also independently
      associated with impairment of daytime functions, poor general health and frequent
      temper outbursts but not caffeine or alcohol intake or cigarette smoking after
      adjustment for age, sex, and other comorbid sleep problems. RLS symptoms
      presented with a modest familial aggregation and heritability (h2+/-SE=0.17+/
      0.04, p<0.001). INTERPRETATION: RLS symptoms are common in Chinese adolescents
      with significant health repercussions. Puberty plays a critical role in the
      emergence of gender difference of RLS symptoms, which are accounted for by both
      genetic and environmental factors.

PMID- 24439694
TI  - Therapeutic sedation for functional (psychogenic) neurological symptoms.
AB  - BACKGROUND: Patients with severe functional (psychogenic) neurological symptoms
      such as paralysis and fixed dystonia present a therapeutic challenge,
      particularly if no movement is possible during physiotherapy. Sedation has been
      discussed as a treatment for functional neurological symptoms for 100 years but
      technique, use of video and outcome has not been systematically described.
      METHODS: Therapeutic sedation of patients with severe functional neurological
      symptoms with propofol and follow up at a neuroscience centre. RESULTS: Of eleven
      patients (median duration 14 months), five were cured or had major improvement
      with sedation. At follow up (median 30 months) four were asymptomatic, two were
      significantly improved and one had minor improvements. We describe a standardized
      anesthetic and physician technique, refined over consecutive treatments.
      CONCLUSION: In carefully chosen patients, therapeutic sedation with propofol can
      be a useful adjunctive treatment for patients with severe functional neurological
      symptoms. The treatment deserves randomized evaluation.

PMID- 24439695
TI  - Pain, pain catastrophizing, and past mental healthcare utilization.
AB  - OBJECTIVE: Pain symptoms have been associated with a number of psychiatric
      disorders, particularly mood and anxiety disorders as well as personality
      disorders. However, to our knowledge, no study to date has examined pain symptoms
      in terms of participants' past mental healthcare utilization--the focus of the
      present study. METHODS: Using a cross-sectional approach and a self-report survey
      methodology in a sample of 242 consecutive internal medicine outpatients, we
      examined pain symptoms at assessment, over the past month, and over the past year
      as well as pain catastrophizing in relationship to 4 mental healthcare variables
      (i.e., ever seen a psychiatrist, ever been in a psychiatric hospital, ever been
      in counseling, and ever been on medication for "nerves"). RESULTS: Only three of
      the four mental-healthcare-utilization variables were analyzed due to response
      rate (i.e., ever been hospitalized in a psychiatric hospital was infrequently
      endorsed and not analyzed), and each demonstrated statistically significant
      relationships with self-reported pain levels at all three time-points and with
      pain catastrophizing at the p<.001 level. CONCLUSIONS: In this study, primary
      care outpatients with histories of mental health treatment evidenced
      statistically significantly higher levels of pain as well as statistically
      significantly higher levels of pain catastrophizing than their peers.

PMID- 24439696
TI  - The rationale for depression screening in patients with coronary heart disease.
      On behalf of the Psychosocial Risk Factors Expert Working Group of the National
      Heart Foundation of Australia.

PMID- 24439697
TI  - Evidence does matter--and evidence does not support the National Heart Foundation
      of Australia's consensus statement on depression screening.

PMID- 24439698
TI  - High resolution T2(*)-weighted Magnetic Resonance Imaging at 3 Tesla using
      PROPELLER-EPI.
AB  - We report the application of PROPELLER-EPI for high resolution T2(*)-weighted
      imaging with sub-millimeter in-plane resolution on a clinical 3 Tesla scanner.
      Periodically rotated blades of a long-axis PROPELLER-EPI sequence were acquired
      with fast gradient echo readout and acquisition matrix of 320 * 50 per blade.
      Images were reconstructed by using 2D-gridding, phase and geometric distortion
      correction and compensation of resonance frequency drifts that occurred during
      extended measurements. To characterize these resonance frequency offsets, short
      FID calibration measurements were added to the PROPELLER-EPI sequence. Functional
      PROPELLER-EPI was performed with volunteers using a simple block design of right
      handed finger tapping. Results indicate that PROPELLER-EPI can be employed for
      fast, high resolution T2(*)-weighted imaging provided geometric distortions and
      possible resonance frequency drifts are properly corrected. Even small resonance
      frequency drifts below 10 Hz as well as non-corrected geometric distortions
      degraded image quality substantially. In the initial fMRI experiment image
      quality and signal-to-noise ratio was sufficient for obtaining high resolution
      functional activation maps.

PMID- 24439699
TI  - Use of psychobehavioral treatment for persons with epilepsy: where are we?

PMID- 24439700
TI  - Stigma experience of people with epilepsy in Mexico and views of health care
      providers.
AB  - Epilepsy is a neurological disorder with neurobiological, cognitive,
      psychological, and social consequences. Epilepsy stigma is a social determinant
      of ill health that affects the quality of life of people who suffer from epilepsy
      and that renders a poor social prognosis even worse than the clinical one. From a
      phenomenological approach, between January and July 2011, we explored the
      experience of epilepsy stigma through 25 in-depth qualitative interviews with 10
      persons with temporal lobe epilepsy (PWE) (we avoided terms such as "epileptics"
      or "epileptic patients" because they can be labeling and stigmatizing), 10 carers
      (CEs) of PWE who attended the epilepsy clinic of the Institute of Neurology and
      Neurosurgery of Mexico, and 5 physicians specialized in epilepsy. The objective
      of the study was to identify the following: perceptions that could indicate any
      form of discrimination due to having epilepsy, reactions of people in front of a
      person having seizures, and social functioning of PWE since epilepsy onset,
      particularly their interpersonal relationships and participation in educational
      or working activities. Through the health providers' narratives, we explored the
      mainstream care practices, their perspectives on epilepsy, and their views about
      how the disease should be addressed. Thematic guidelines were elaborated for each
      type of participant. All information was processed with the use of the computer
      assisted data analysis, Atlas.ti5. We made a codification of broad themes that
      corresponded to the main topics of the interview guidelines and then proceeded to
      finer categorization to elaborate the analytical categories. Epilepsy was
      attached to a powerful stereotype that includes notions of contamination, danger,
      sin, divine punishment, supernatural forces, and madness. Internalized,
      interpersonal, and institutional stigma prevents PWE from participating in school
      and employment and reduces their opportunities to establish peer and couple
      relationships. Mexican's overt impunity of structural discrimination towards PWE
      shows a lack of available legal resources that protect their human rights. The
      narrow biomedical concept that physicians have of epilepsy is consistent with the
      limited medical practices that are offered to treat epilepsy at the health
      services in Mexico. Comprehensive treatment and integrated services for epilepsy
      must incorporate psychosocial programs that include epilepsy stigma as a major
      component of the disease. 

PMID- 24439701
TI  - A cross-sectional study of the presence of United Kingdom (UK) plastic surgeons
      on social media.
AB  - INTRODUCTION AND AIMS: To determine the uptake and usage of websites and social
      media (SM) by UK consultant (attending) plastic surgeons. METHODS: Professional
      profiles of full BAPRAS members were searched on Facebook, Twitter, LinkedIn,
      RealSelf, YouTube, ResearchGate in May 2013. Additional surgeons were identified
      from the follower lists of @BAPRASvoice and @BAAPSMedia. Website ownership was
      determined on Google. Searches were repeated three times. Dual BAAPS-BAPRAS
      members were identified from www.baaps.org.uk. RESULTS: There were 156 (48.3%)
      dual BAAPS-BAPRAS members and 36 BAPRAS-only members. Fifty seven (18%) surgeons
      had no account on any platform whereas 266 (82%) were on at least one platform.
      One hundred and sixty four (51%) had personal websites whilst 37 (11%) had
      profiles on partnership websites. One hundred and sixteen (36%) had no website
      presence whilst 2% had websites under construction. The platform most surgeons
      use is LinkedIn (52%) whilst smaller proportions used Facebook (4%) and Twitter
      (22%). Surgeons had a mean of 126 (range: 0-3270) Twitter followers and 368
      (range: 7-3786) fans/'likes' of their Facebook profiles. Time spent in
      postgraduate practice was not predictive of website ownership or SM use. However,
      dual BAAPS-BAPRAS members were significantly more likely to own a personal
      website, Twitter, RealSelf and YouTube accounts. CONCLUSIONS: There has been an
      increase in the uptake of social media by UK plastic surgeons, especially in
      those with aesthetic surgery interests. However, very few surgeons have optimised
      their web presence. Continued education and appropriate usage guidance may
      promote uptake, particularly by reconstructive surgeons.

PMID- 24439711
TI  - Establishing expertise: Canadian community-based medical cannabis dispensaries as
      embodied health movement organisations.
AB  - In this commentary, I describe how, through both advocacy and the generation of
      new knowledge, community-based medical cannabis dispensaries have contributed to
      the broader dialogue regarding the legal and safe provision of medical cannabis
      in Canada. By employing an embodied health movement framework (Brown et al.,
      2004), this analysis highlights the role of dispensaries in creating new
      knowledge, challenging existing practices, and advancing their agenda to
      legitimise cannabis as a therapeutic substance and offer an alternative model for
      its provision. Although the community-based, holistic approach that dispensaries
      offer has not been adopted by the Canadian government, dispensaries have achieved
      success in being recognized as credible stakeholders and experts in the ongoing
      debate on the legal provision of medical cannabis in Canada. 

PMID- 24439710
TI  - The economic geography of medical cannabis dispensaries in California.
AB  - BACKGROUND: The introduction of laws that permit the use of cannabis for medical
      purposes has led to the emergence of a medical cannabis industry in some US
      states. This study assessed the spatial distribution of medical cannabis
      dispensaries according to estimated cannabis demand, socioeconomic indicators,
      alcohol outlets and other socio-demographic factors. METHODS: Telephone survey
      data from 5940 residents of 39 California cities were used to estimate social and
      demographic correlates of cannabis consumption. These individual-level estimates
      were then used to calculate aggregate cannabis demand (i.e. market potential) for
      7538 census block groups. Locations of actively operating cannabis dispensaries
      were then related to the measure of demand and the socio-demographic
      characteristics of census block groups using multilevel Bayesian conditional
      autoregressive logit models. RESULTS: Cannabis dispensaries were located in block
      groups with greater cannabis demand, higher rates of poverty, alcohol outlets,
      and in areas just outside city boundaries. For the sampled block groups, a 10%
      increase in demand within a block group was associated with 2.4% greater
      likelihood of having a dispensary, and a 10% increase in the city-wide demand was
      associated with a 6.7% greater likelihood of having a dispensary. CONCLUSION:
      High demand for cannabis within individual block groups and within cities is
      related to the location of cannabis dispensaries at a block-group level. The
      relationship to low income, alcohol outlets and unincorporated areas indicates
      that dispensaries may open in areas that lack the resources to resist their
      establishment.

PMID- 24439712
TI  - Clinical, laboratory, diagnostic, and histopathologic features of diethylene
      glycol poisoning--Panama, 2006.
AB  - STUDY OBJECTIVE: Diethylene glycol is a toxic industrial solvent responsible for
      more than 13 mass poisonings since 1937. Little is known about the clinical
      spectrum, progression, and neurotoxic potential of diethylene glycol-associated
      disease because of its high mortality and the absence of detailed information in
      published mass poisoning reports. This incident includes the largest proportion
      of cases with neurotoxic signs and symptoms. We characterize the features of a
      diethylene glycol mass poisoning resulting from a contaminated cough syrup
      distributed in Panama during 2006. METHODS: This was a retrospective chart review
      and descriptive analysis in a tertiary level, urban health care facility. A case
      was a person admitted to the Social Security Metropolitan Hospital in Panama City
      between June 1 and October 22, 2006, with unexplained acute kidney injury and a
      serum creatinine level of greater than or equal to 2 mg/dL, or unexplained
      chronic renal failure exacerbation (>2-fold increase in baseline serum creatinine
      level) and history of implicated cough syrup exposure. Main outcomes and measures
      were demographic, clinical, laboratory, diagnostic, histopathologic, and
      mortality data with descriptive statistics. RESULTS: Forty-six patients met
      inclusion criteria. Twenty-four (52%) were female patients; median age was 67
      years (range 25 to 91 years). Patients were admitted with acute kidney injury or
      a chronic renal failure exacerbation (median serum creatinine level 10.0 mg/dL) a
      median of 5 days after symptom onset. Forty patients (87%; 95% confidence
      interval [CI] 74% to 95%) had neurologic signs, including limb (n=31; 77%; 95% CI
      62% to 89%) or facial motor weakness (n=27; 68%; 95% CI 51% to 81%).
      Electrodiagnostics in 21 patients with objective weakness demonstrated a severe
      sensorimotor peripheral neuropathy (n=19; 90%; 95% CI 70% to 99%). In 14 patients
      without initial neurologic findings, elevated cerebrospinal fluid protein
      concentrations without pleocytosis were observed: almost all developed overt
      neurologic illness (n=13; 93%; 95% CI 66% to 100%). Despite use of intensive care
      and hemodialysis therapies, 27 (59%) died a median of 19 days (range 2 to 50
      days) after presentation. CONCLUSION: A high proportion of patients with
      diethylene glycol poisoning developed progressive neurologic signs and symptoms
      in addition to acute kidney injury. Facial or limb weakness with unexplained
      acute kidney injury should prompt clinicians to consider diethylene glycol
      poisoning. Elevated cerebrospinal fluid protein concentrations without
      pleocytosis among diethylene glycol-exposed persons with acute kidney injury may
      be a predictor for progressive neurologic illness.

PMID- 24439713
TI  - A non-inferiority randomized controlled trial comparing the clinical
      effectiveness of anesthesia obtained by application of a novel topical anesthetic
      putty with the infiltration of lidocaine for the treatment of lacerations in the
      emergency department.
AB  - STUDY OBJECTIVE: We test the hypothesis that anesthesia, measured as pain scores,
      induced by a novel topical anesthetic putty is non-inferior (margin=1.3) to that
      provided by conventional lidocaine infiltration for the repair of lacerations.
      METHODS: A randomized controlled trial was conducted in the emergency department
      (ED) of a local hospital. Participants were randomly allocated to receive either
      infiltration anesthesia or topical anesthetic putty as per the trial protocol.
      Pain scores were recorded 15 minutes after infiltration and 30 minutes after
      topical anesthetic putty application. Median pain scores were compared between
      groups. Wound evaluation scores were conducted after 7 to 10 days and adverse
      events were monitored for both groups of participants throughout the study.
      RESULTS: One hundred and ten participants were enrolled in the study, with 56
      receiving infiltration and 54 receiving topical anesthetic putty. The median
      difference between the pain scores of the 2 groups was 0 (95% confidence interval
      -1 to 0). There were no substantial differences between the 2 groups in terms of
      either the wound evaluation scores or the incidence of adverse events.
      CONCLUSION: The novel topical anesthetic putty was not inferior to infiltration
      with lidocaine with respect to the pain experienced during suturing, and this
      putty is a feasible alternative to infiltration anesthesia of lacerations in the
      ED.

PMID- 24439714
TI  - The FLUSH study--flush the line and ultrasound the heart: ultrasonographic
      confirmation of central femoral venous line placement.
AB  - STUDY OBJECTIVE: Inadvertent arterial placement of a femoral venous catheter may
      result in serious morbidity, including limb necrosis. The Flush the Line and
      Ultrasound the Heart (FLUSH) test is visualization of the heart by a subxiphoid
      ultrasonic view while the central catheter is flushed with agitated saline
      solution. We wish to determine whether the FLUSH test can verify proper femoral
      venous line placement. METHODS: We prospectively studied a convenience sample of
      children undergoing cardiac catheterization, for whom both femoral venous and
      arterial access were part of their standard care. The cardiologist flushed
      manually agitated saline solution through each catheter in randomized sequence
      while the blinded physician sonographer recorded the presence or absence of right
      atrial opacification. We calculated the sensitivity and specificity of the FLUSH
      test relative to our reference standard, the cardiologist's fluoroscopic
      visualization of catheter wire placement. RESULTS: Of the 51 subjects enrolled,
      the FLUSH test was 100% sensitive (95% confidence interval 95% to 100%) and 90.3%
      specific (95% confidence interval 81% to 96%) in confirming femoral catheter
      placement. In no case was an arterial flush misidentified as a femoral flush. The
      interrater reliability of the test was strong: kappa 0.82 for all images and 0.9
      for those of good quality. CONCLUSION: The FLUSH test is simple and reliable, and
      appears to accurately confirm femoral venous line placement.

PMID- 24439715
TI  - Ambulatory management of large spontaneous pneumothorax with pigtail catheters.
AB  - STUDY OBJECTIVE: There is no consensus about the management of large spontaneous
      pneumothoraces. Guidelines recommend either needle aspiration or chest tube
      drainage and most patients are hospitalized. We assess the efficiency of
      ambulatory management of large spontaneous pneumothoraces with pigtail catheters.
      METHODS: From February 2007 to January 2011, all primary and secondary large
      spontaneous pneumothoraces from Lorient's hospital (France) were managed with
      pigtail catheters with a 1-way valve. The patients were discharged immediately
      and then evaluated every 2 days according to a specific algorithm. RESULTS: Of
      the 132 consecutive patients (110 primary, 22 secondary), 103 were exclusively
      managed as outpatients, with full resolution of the pneumothorax by day 2 or 4,
      which represents an ambulatory success rate of 78%. Mean time (SD) of drainage
      was 3.4 days (1.8). Seven patients were initially hospitalized but quickly
      discharged and had full resolution by day 2 or 4, leading to a total success rate
      of 83%. The use of analgesics was low. The 1-year recurrence rate was 26%. If
      successful, this outpatient management is potentially cost saving, with a mean
      cost of $926, assuming up to 2 outpatient visits and 1 chest radiograph, compared
      with $4,276 if a chest tube was placed and the patient was admitted to the
      hospital for 4 days. CONCLUSION: Ambulatory management with pigtail catheters
      with 1-way valves could be a reasonable first-line of treatment for large
      spontaneous pneumothoraces. Compared with that of other studies, our protocol
      does not require hospitalization and is cost saving.

PMID- 24439716
TI  - Can procalcitonin differentiate sepsis from systemic inflammatory response
      syndrome without infection?

PMID- 24439717
TI  - Clinical utility of an age-adjusted D-dimer in the diagnosis of venous
      thromboembolism.

PMID- 24439718
TI  - Feto-maternal outcomes of pregnancy complicated by ovarian sex-cord stromal
      tumor: a systematic review of literature.
AB  - Sex-cord stromal tumors (SCSTs) are rare ovarian cancers and their behavior
      during pregnancy is not well understood. To evaluate the maternal and fetal
      outcomes of pregnancy complicated by ovarian SCST, a systematic literature search
      was conducted in PubMed/MEDLINE using entry key words "pregnancy" and each type
      of ovarian SCST ("sex cord stromal tumor," "granulosa cell tumor," "thecoma,"
      "Sertoli-Leydig cell tumor," or "gynandroblastoma") between 1955 and 2012 that
      identified 46 cases eligible for the analysis. Clinical characteristics,
      pregnancy outcome, tumor characteristics, and survival outcomes were evaluated.
      Serious adverse events were defined as complications related to the SCST that
      resulted in severe morbidity or mortality for mother, fetus, or both. The most
      common histology was granulosa cell tumor (22.0%), followed by thecoma (18.6%)
      and Sertoli-Leydig cell tumor (8.5%). Abdomino-pelvic pain (45.7%), palpable mass
      (30.4%), and virilization (26.1%) were the three most common symptoms. The
      majority were stage I (76.1%), tumor size <15cm (64.9%), and underwent unilateral
      adnexectomy (80.4%). Fetal conservation surgery was seen in 54.3%. Most cases had
      live births (78.3%) at full term (60.9%). Among cases proceeded expectant delay
      of delivery (45.7%), most cases resulted in live birth (95.2%) with median
      expectant interval of 20.7 weeks. Maternal and/or fetal serious adverse events
      (SAEs) were observed in 41.3% with maternal shock/hemoperitoneum being the most
      common complication (13.0%). Logistic regression test identified younger age (<30
      versus >=30, 73.3% versus 26.7%, odds ratio [OR] 11.7, 95%CI 1.35-101, p=0.026),
      large tumor (size >=15cm versus <15cm, 64.9% versus 35.1%, OR 10.0, 95%CI 1.29
      26.2, p=0.004), and advanced-stage (stages II-IV versus I, 76.1% versus 23.9%, OR
      5.82, 95%CI 2.05-48.9, p=0.022) as risk factors of increased SAE. Overall
      survival of patients diagnosed with ovarian SCST during pregnancy was comparable
      to ovarian SCST not related to pregnancy (5-year rate, stages I and II-IV, 100%
      and 70.0%, respectively). In conclusion, although the majority of cases resulted
      in live birth, ovarian SCST-complicated pregnancy falls into the category of high
      risk pregnancy. Risk factors for SAE identified in our study will help to guide
      strategic management of pregnancy complicated by ovarian SCST. 

PMID- 24439719
TI  - A pilot study on peak systolic velocity monitoring of fetal anemia after
      administration of chemotherapy during pregnancy.
AB  - OBJECTIVES: To monitor fetal anemia during administration of chemotherapy to the
      fetus's mother. STUDY DESIGN: Between 2007 and 2012 six patients with malignancy
      diagnosed during pregnancy were included in our prospective study. For evaluation
      of fetal anemia, peak systolic velocimetry (PSV) of the middle cerebral artery is
      considered the best method. The patients were repeatedly examined one day before
      and on the third day after the administration of chemotherapy. At least three
      measurements were performed and the highest value was used as appropriate.
      Multiples of the median (MoM) were calculated using the website
      http://www.perinatology.com/calculators/MCA.htm. When the MoM reached 1.29,
      moderate anemia was diagnosed. RESULTS: The women's average age was 30 years. The
      average gestational age at diagnosis was 20.7 weeks of pregnancy. Borderline
      fetal anemia was detected in only in one patient. After delivery newborns were
      examined by standard pediatric evaluation and blood count was provided. There was
      no evidence of any newborn anemia. CONCLUSIONS: Chemotherapy administered during
      pregnancy is becoming more frequent due to increasing knowledge and data on such
      cases. Close monitoring of the fetus should be performed in specialized centers.
      For detection of chemotherapy-induced anemia, PSV measurement should be employed.

PMID- 24439720
TI  - [Ultrasonography in chronic inflammatory rheumatic and connective tissue
      disorders].
AB  - Musculoskeletal ultrasonography is now widely used by almost all rheumatologists
      thanks to an improvement in the quality of ultrasound unit and probe and to the
      systematic teaching of this imaging technique to the rheumatology fellows.
      Applications have broadened from the study of degenerative and mechanical
      diseases to inflammatory rheumatic diseases. Ultrasound is more sensitive than
      clinical examination. Power Doppler allows the direct visualisation of
      inflammation within the tissues. Finally, it is a prognostic tool helping the
      physician in the management of the disease. This review will focus on the value
      and applications of ultrasonography in the 2 most frequent rheumatic diseases:
      rheumatoid arthritis and spondyloarthritis. We will also give some recent data on
      the usefulness of this imaging technique in the study of musculoskeletal
      manifestations associated with connective tissue disease. 

PMID- 24439721
TI  - Ruptured bronchial artery aneurysm in patient with unknown trauma or lung
      disease.

PMID- 24439722
TI  - Time trends in prevalence of activities of daily living (ADL) disability and
      survival: comparing two populations (aged 78+ years) living in a rural area in
      Sweden.
AB  - The aim was to study time trends in prevalence of disability in ADL and survival
      among men and women 78 years and older comparing two cohorts. The study was a
      time trend study based on two population-based community cohorts, the Nordanstig
      Project (NP), collected 1995-1998 and the Swedish National Study on Aging and
      Care in Nordanstig (SNAC-N), collected 2001-2003. The participants were people
      aged 78 years and older from the NP cohort (N=303) and from the SNAC-N cohort
      (N=406). All were clinically examined by physicians and nurses using standardized
      protocols. Disability was defined as a need for assistance in one or more ADL
      activities. The prevalence of disability and survival were compared using
      logistic and Cox models. The prevalence of ADL disability was stable for men,
      while women became more disabled in ADL during the time period, OR 2.36 (1.12
      4.94). There was no significant difference in survival time between the cohorts
      in either ADL disabled persons or non-disabled persons. There was a tendency for
      increased survival for non-disabled persons in SNAC-N compared with NP, although
      not significant; this was particularly true for women. In general, women survived
      longer than men did regardless of whether they were ADL disabled or not. The time
      trends for ADL disability found in the study show that ADL disability had
      increased in women but not in men. More studies are needed to identify risk
      factors for ADL disability with a view to preventing it in time. 

PMID- 24439724
TI  - Active surveillance for early-stage prostate cancer.

PMID- 24439723
TI  - Long-term food restriction prevents aging-associated sphingolipid turnover
      dysregulation in the brain.
AB  - Abnormalities of sphingolipid turnover in the brain during normal aging and age
      related neurological disorders were associated with the neurons loss and
      cognitive malfunction. Calorie restriction (CR) prevented age-related deficits in
      hippocampal long-term potentiation and improved cognitive function at old age. In
      the paper we investigated the ceramide and sphingomyelin (SM) levels in the brain
      regions, which are critical for learning and memory of 3- and 24-month-old rats,
      as well as the correction of sphingolipid turnover in the brain of old rats, by
      means of the CR diet and modulators of SM turnover. Using the [methyl-(14)C
      choline]SM, the neutral, but not the acid SMase activity has been observed to
      increase in both the hippocampus and brain cortex of 24-month-old rats with
      respect to 3-month-old animals. Age-dependent changes of neutral SMase activities
      were associated with ceramide accumulation and SM level drop in the brain
      structures studied. Treatment of the rats with the CR diet or N-acetylcysteine
      (NAC) or alpha-tocopherol acetate, but not an inhibitor of acid SMase imipramine,
      reduced the ceramide content and neutral SMase activity in the hippocampus of 24
      month-old animals with respect to control rats of the same age. These results
      suggest that redox-sensitive neutral SMase plays important role in SM turnover
      dysregulation in both the hippocampus and neocortex at old age and that the CR
      diet can prevent the age-dependent accumulation of ceramide mainly via neutral
      SMase targeting. 

PMID- 24439725
TI  - Reproductive health in the USA: must do better.

PMID- 24439726
TI  - Nuanced risk assessment for emerging infectious diseases.

PMID- 24439729
TI  - Design of pragmatic trials of tuberculosis interventions.

PMID- 24439730
TI  - Shortage of public health independence and advocacy in the UK.

PMID- 24439731
TI  - Design of pragmatic trials of tuberculosis interventions - authors' reply.

PMID- 24439732
TI  - Design of pragmatic trials of tuberculosis interventions.

PMID- 24439733
TI  - Mozambique faces challenges in the fight against tuberculosis.

PMID- 24439734
TI  - Reversing the tide of the UK tuberculosis epidemic.

PMID- 24439735
TI  - Calcium-based phosphate binders and chronic kidney disease.

PMID- 24439736
TI  - Immunisation against meningococcus B: the case of Spain.

PMID- 24439737
TI  - Should we screen blood products for hepatitis E virus RNA ?

PMID- 24439738
TI  - Imaging-negative psoas abscess.

PMID- 24439739
TI  - Insufficient safety measures reported in operation notes of complicated
      laparoscopic cholecystectomies.
AB  - BACKGROUND: In 2007, a Dutch guideline for laparoscopic cholecystectomy (LC) was
      composed that advocates the critical view of safety (CVS) to prevent bile duct
      injury (BDI). Conversion to open cholecystectomy is recommended in complicated
      cholecystectomy, but young surgeons are hardly trained in this procedure. The aim
      of this study was to analyze the accuracy of dictated operation notes, the use of
      CVS before and after guideline implementation, and the severity of injury after
      conversion. METHODS: Between 1990 and 2012, 800 patients were referred for
      treatment of BDI. All available operation notes (n = 528; 66%) were scored for
      procedural conditions, reasons for conversion, the use of safety measures, and
      postoperative care in BDI patients. RESULTS: Patient demographics, indication for
      cholecystectomy, conversion rates, and injury type were comparable to the total
      cohort of BDI patients. LC (n = 479; 91%) was converted in 180 patients (34%).
      The CVS technique or dissection of Calot's triangle were reported in 33 patients
      (6.3%) and 87 patients (16.5%), respectively. Guideline implementation increased
      the reporting of CVS from 4% (16/425) to 17% (17/103; P < .001), and the
      consultation of a hepatic-pancreatic-biliary (HPB) colleague from 3% (14/425) to
      8% (8/103; P < .01). Conversion to open surgery leads to more complex injury
      (Bismuth III-V injury rate of 34% [24/64] vs 65% [46/116]; P = .013). CONCLUSION:
      The insufficient use of safety measures to prevent BDI during LC in this selected
      patient group is of concern. Although guideline implementation significantly
      improved the use of CVS during LC, further improvement is necessary. Conversion
      cannot simply be used as an "escape" procedure, because this may lead to more
      complex injury.

PMID- 24439740
TI  - The clinical importance of a transcription reverse-transcription concerted (TRC)
      diagnosis using peritoneal lavage fluids in gastric cancer with clinical serosal
      invasion: a prospective, multicenter study.
AB  - PURPOSE: We have developed a novel molecular method of diagnosis using the
      technique of transcriptase-reverse transcriptase concerted reaction (TRC) for the
      detection of cancer micrometastasis. This study prospectively examined the
      clinical importance of the TRC diagnosis with peritoneal lavage fluids collected
      from gastric cancer operations at multiple institutes. METHODS: TRC amplification
      targeting carcinoembryonic antigen mRNA was applied to detect gastric cancer
      cells in peritoneal lavage fluids obtained during gastric cancer resections from
      nine different hospitals. A total of 137 patients with a clinical diagnosis of
      serosa-invading neoplasms were enrolled to investigate the correlation between
      the TRC diagnosis and patient prognosis. RESULTS: Of the 137 patients, 27 (20%)
      were positive by cytologic examination. In contrast, TRC targeting
      carcinoembryonic antigen mRNA was positive in 59 of 137 (54%) patients. TRC
      positivity was associated with a poorer overall survival in all patients and in
      the 104 patients who underwent a curative operation. TRC positivity also was
      associated with the peritoneal recurrence-free survival rate in the 104 curative
      cases. Multivariate analysis showed that TRC positivity and the pathologic N
      factor were prognostic factors for the overall survival time. CONCLUSION: Our
      prospective multicenter study showed that the TRC test using peritoneal lavage
      fluids could be a potential prognostic factor to predict patient survival and
      peritoneal recurrence with clinically diagnosed, serosa-invading gastric cancer.

PMID- 24439741
TI  - Randomized controlled trial comparing subcuticular absorbable suture with
      conventional interrupted suture for wound closure at elective operation of colon
      cancer.
AB  - BACKGROUND: Subcuticular closure provides a superior cosmetic result in clean
      wounds. The aim of this work was to investigate the safety in terms of
      postoperative infection and cosmetic effectiveness of subcuticular wound closure
      after elective colon cancer surgery in clean-contaminated wounds. METHODS:
      Patients who underwent elective resection of colon cancer were randomized to
      interrupted subcuticular and interrupted transdermal suture groups. The large
      bowel was prepared by mechanical washout with polyethylene glycol. All patients
      received metronidazole and kanamycin orally and flomoxef sodium once parenterally
      for antimicrobial prophylaxis. The primary end point was the incidence of
      incisional surgical-site infections within 30 days after operation. We assessed
      noninferiority of subcuticular suture within a margin of 10%. Analysis was by
      intent-to-treat. Secondary objectives include comparison of wound closure time,
      comfort, and cosmesis of the scar and satisfaction of patients. This study was
      registered with UMIN-CTR, UMIN000003005. RESULTS: A total of 293 patients were
      randomized to the two groups. Incisional surgical-site infection rates were 11.0%
      (90% confidence interval 7.0-16.3%) for both groups. The relative risk of
      subcuticular suture was 1.00 (0.58-1.73, one-tail P = .57). Interrupted
      subcuticular suture was noninferior to interrupted transdermal suture (P =
      .0088). Throughout 6 months after operation, patients expressed a significant
      preference for the subcuticular suture technique, noting rapid relief from pain,
      decreased vascularity, and smaller width, although the procedure took twice as
      long. CONCLUSION: Subcuticular suture did not increase the incidence of wound
      complications in elective colon cancer operation. Patients preferred a technique
      of interrupted subcuticular closure, citing better cosmetic results, and less
      pain.

PMID- 24439742
TI  - Systematically Tabulated Outcomes Research Matrix (STORM): a methodology to
      generate research hypotheses.
AB  - BACKGROUND: Here we describe the Systematically Tabulated Outcomes Research
      Matrix (STORM) method to generate research questions from pre-existing databases
      with the aim of improving patient outcomes. MATERIALS AND METHODS: STORM can be
      applied to a database by tabulating its variables into a matrix of independent
      variables (y-axis) and dependent variables (x-axis) and then applying each unique
      pairing of an independent and dependent variable to a patient population to
      generate potentially meaningful research questions. RESULTS: To demonstrate this
      methodology and establish proof-of-principle, STORM was applied on a small scale
      to the National Trauma Data Bank and generated at least seven clinically
      meaningful research questions. CONCLUSION: When coupled with rigorous clinical
      judgment, the STORM approach complements the traditional method of hypothesis
      formation and can be generalized to outcomes research using registry databases
      across different medical specialties.

PMID- 24439743
TI  - Commentary on: impact of reconstruction method on visceral fat change after
      distal gastrectomy: results from a randomized controlled trial comparing Billroth
      I reconstruction and roux-en-Y reconstruction.

PMID- 24439744
TI  - Evaluation of the safety and efficacy of simultaneous resection of primary
      colorectal cancer and synchronous colorectal liver metastases.
AB  - BACKGROUND: It remains unclear whether primary colorectal cancer and synchronous
      liver metastases (SLMs) should be resected simultaneously or with a staged
      procedure. METHODS: We reviewed the short-term outcomes of 127 patients who
      underwent simultaneous resection of primary colorectal cancer and SLM at our
      institution from January 1993 to December 2011. RESULTS: The proportion of
      simultaneous resections was 84.7% (127 of 150 patients). There was no
      postoperative mortality, and the postoperative complication rate was 61.4%. Major
      complications occurred in 23 (18.2%) patients, and anastomotic failure occurred
      in 2 (1.6%). The 3-, 5-, and 10-year overall survival rates were 74%, 64%, and
      52%, respectively. The median recurrence-free survival period was 7.0 months (95%
      confidence interval, 4.5-9.5 months) and the 5-year recurrence-free survival rate
      was 17%. CONCLUSION: Simultaneous resection can be performed safely in patients
      with colorectal cancer and SLM.

PMID- 24439745
TI  - Prioritizing essential surgery and safe anesthesia for the Post-2015 Development
      Agenda: operative capacities of 78 district hospitals in 7 low- and middle-income
      countries.
AB  - BACKGROUND: Surgery has been neglected in low- and middle-income countries for
      decades. It is vital that the Post-2015 Development Agenda reflect that surgery
      is an important part of a comprehensive global health care delivery model. We
      compare the operative capacities of multiple low- and middle-income countries and
      identify critical gaps in surgical infrastructure. METHODS: The Harvard
      Humanitarian Initiative survey tool was used to assess the operative capacities
      of 78 government district hospitals in Bangladesh (n = 7), Bolivia (n = 11),
      Ethiopia (n = 6), Liberia (n = 11), Nicaragua (n = 10), Rwanda (n = 21), and
      Uganda (n = 12) from 2011 to 2012. Key outcome measures included infrastructure,
      equipment availability, physician and nonphysician surgical providers, operative
      volume, and pharmaceutical capacity. RESULTS: Seventy of 78 district hospitals
      performed operations. There was fewer than one surgeon or anesthesiologist per
      100,000 catchment population in all countries except Bolivia. There were no
      physician anesthesiologists in any surveyed hospitals in Rwanda, Liberia, Uganda,
      or in the majority of hospitals in Ethiopia. Mean annual operations per hospital
      ranged from 374 in Nicaragua to 3,215 in Bangladesh. Emergency operations and
      obstetric operations constituted 57.5% and 40% of all operations performed,
      respectively. Availability of pulse oximetry, essential medicines, and key
      infrastructure (water, electricity, oxygen) varied widely between and within
      countries. CONCLUSION: The need for operative procedures is not being met by the
      limited operative capacity in numerous low- and middle-income countries. It is of
      paramount importance that this gap be addressed by prioritizing essential surgery
      and safe anesthesia in the Post-2015 Development Agenda.

PMID- 24439746
TI  - Preconditioning with thyroid hormone (3,5,3-triiodothyronine) prevents renal
      ischemia-reperfusion injury in mice.
AB  - BACKGROUND: 3,5,3-triiodothyronine (T3) was found to decrease ischemia
      reperfusion (I/R) injury of liver and myocardium in animal models when
      preconditioned 48 hours in advance of the I/R injury. The purpose of this study
      was to evaluate the effects of T3 preconditioning on renal I/R injury with
      different time intervals and to determine the changes in antioxidants, apoptosis,
      and nitric oxide synthase (NOS) in each condition. METHODS: In male C57BL/6 mice,
      renal I/R injury was induced by temporary ligation of the bilateral renal
      pedicles for 45 minutes followed by a reperfusion period for 24 hours.
      Preconditioning with intraperitoneal injection of T3 was performed 24 or 6 hours
      before or at the time of I/R injury. RESULTS: From the histologic examination,
      tubular injury was decreased in mice preconditioned with T3 6 hours before I/R
      injury. The levels of proinflammatory cytokines were decreased with T3
      preconditioning, either 6 hours or at the time of I/R injury. The levels of
      glutathione were increased in all treatment groups. Expressions of neuronal NOS
      were increased when preconditioned 6 hours before or at the time of I/R injury.
      The number of apoptotic tubular epithelial cell evaluated by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was decreased
      when preconditioned immediately before I/R injury. CONCLUSION: Preconditioning
      with T3 6 hours or immediately before I/R injury had a protective effect on renal
      I/R injury. The changes of NOS and antiapoptosis, other than well-known
      antioxidative properties, may play a role in the effect of short-term
      preconditioning.

PMID- 24439747
TI  - Anatomic versus nonanatomic resection in cirrhotic patients with early
      hepatocellular carcinoma.
AB  - BACKGROUND: Whether anatomic resection (AR) for hepatocellular carcinoma (HCC)
      can really confer a survival advantage over non-AR (NAR), especially for
      cirrhotic patients, remains unclear. METHODS: Prospectively collected data of 543
      cirrhotic patients in Child-Pugh class A submitted to AR (n = 228) versus NAR (n
      = 315) for early HCC in an Eastern (n = 269) and a Western (n = 274) surgical
      unit, were reviewed. To control for confounding variable distributions, a 1-to-1
      propensity score match was applied to compare AR and NAR outcomes (n = 298).
      RESULTS: The 5-year recurrence-free and overall survivals of the 543 patients
      were 32.3% and 60.0%, respectively, without differences between the 2 centers (P
      = .635 and .479, respectively). AR conferred better overall and recurrence-free
      survival than NAR (P = .009 and .041, respectively), but NAR patients suffered
      from significantly worse hepatic dysfunction. After 1-to-1 match, AR (n = 149)
      and NAR (n = 149) patients had similar covariate distributions. In this matched
      sample, AR still conferred better recurrence-free survival over NAR (P = .044)
      but the beneficial effect of AR was limited to the reduction of early recurrence
      (<2 years) of poorly differentiated tumors and of tumors with microvascular
      invasion (P < .05), resulting in better overall survival (P = .018). CONCLUSION:
      In cirrhotic patients, AR for early HCC can lead to a lower early recurrence rate
      in tumors with unfavorable tumor features, whereas NAR will not worsen the
      recurrence rate in well/moderately differentiated tumors or in the absence of
      microvascular invasion.

PMID- 24439748
TI  - Exposing endothelial cells to tumor necrosis factor-alpha and peripheral blood
      mononuclear cells damage endothelial integrity via interleukin-1beta by
      degradation of vascular endothelial-cadherin.
AB  - BACKGROUND AND PURPOSE: We demonstrated previously that the administration of
      tumor necrosis factor alpha (TNF-alpha) for the treatment of solid tumors
      enhanced the response to chemotherapy by augmenting intratumoral drug
      accumulation. TNF-alpha changes the integrity of the endothelial cell monolayer
      in combination with interferon gamma (IFN-gamma), which is further enhanced by
      the addition of peripheral blood mononuclear cells (PBMCs). The improved effect
      of PBMCs was mostly induced by the endogenous production of interleukin-1beta (IL
      1beta) after TNF-alpha stimulation. In the current study, we demonstrate that
      exposing endothelial cells to TNF-alpha and PBMCs mediates the loss of vascular
      endothelial (VE)-cadherin, an important adherens junction protein for maintaining
      endothelial integrity, through endogenous IL-1beta. This loss increases
      permeability of the endothelial layer, thereby explaining the augmented passage
      of chemotherapeutics into the tumor. METHODS: Human umbilical vein endothelial
      cells were exposed to TNF-alpha, IFN-gamma, PBMCs, or IL-1beta, and the effects
      on the endothelial integrity were assessed by morphological changes and
      permeability changes with the use of fluorescein isothiocyanate-labeled bovine
      serum albumin flux. The loss of VE-cadherin was assessed using
      immunofluorescence, western blotting, and polymerase chain reaction. RESULTS:
      Incubating endothelial cells with TNF-alpha, IFN-gamma, and PBMCs increased cell
      elongation, gap formation, and subsequently the permeability of fluorescein
      isothiocyanate-labeled bovine serum albumin compared with control or TNF-alpha
      and IFN-gamma-treated cells (P < .05). When PBMCs were replaced with IL-1beta,
      identical changes were observed. These changes in integrity were associated with
      a loss of VE-cadherin at the membrane. CONCLUSION: We conclude that VE-cadherin
      is lost at the membrane when endothelial cells are exposed to TNF-alpha, IFN
      gamma, and PBMCs, which results in loss of integrity. IL-1beta can mimic the
      effects of PBMCs, indicating a dominant role of endogenously produced IL-1beta in
      this process.

PMID- 24439749
TI  - The preoperative evaluation: medical necessity or unnecessary expense?

PMID- 24439750
TI  - Does pathologic response of rectal cancer influence postoperative morbidity after
      neoadjuvant radiochemotherapy and total mesorectal excision?
AB  - BACKGROUND: A pathologic complete response (pCR) can be observed in up to 25% of
      patients after preoperative chemoradiotherapy for rectal cancer and is associated
      with an improved long-term prognosis. However, few data are available regarding
      the effect of pCR on postoperative morbidity. This study aimed to assess the
      impact of the pCR on postoperative outcomes after laparoscopic total mesorectal
      excision (TME). METHODS: A prospectively maintained database (2006-2011) was
      reviewed for all consecutive patients (n = 143) undergoing laparoscopic TME for
      mid or low rectal cancer after neoadjuvant chemoradiotherapy. Postoperative data
      were compared for pCR-group and non-pCR-group. A pCR was defined as the absence
      of gross and microscopic tumor in the specimen, irrespective of the nodal status
      (ypT0). RESULTS: Thirty-three patients (23%) had a pCR. Median operating time was
      greatly shorter in the pCR-group (230 minutes, 180-360), compared with the non
      pCR-group (240 minutes, 130-420, P = .02). Lymph node involvement was noted for
      12% of the patients in the pCR-group and 33% of the patients in the non-pCR-group
      (P = .91). Clavien Dindo grade 3 and 4 complications (6% vs 22%, P = .04),
      infection related morbidity (47% vs 76%, P = .04), and clinical anastomotic
      leakage rates (9% vs 29%, P = .02) were lesser in the pCR group compared with the
      non-pCR group. Mean duration of hospital stay was lesser in the pCR-group (9 vs
      12 days, P = .01). CONCLUSION: This study showed that Clavien Dindo grade 3 and 4
      complications, including anastomosis leakage, and infection related complications
      rates were lesser in patients with pathologic complete response after RCT and
      laparoscopic TME for rectal cancer.

PMID- 24439751
TI  - Predicting the underestimation of the femoral offset in anteroposterior
      radiographs of the pelvis using 'lesser trochanter index': a 3D CT derived
      simulated radiographic analysis.
AB  - We developed 'lesser trochanter index' (LTI) and estimated its accuracy in
      predicting the underestimation of offset in the anteroposterior (AP) pelvic
      radiographs. We reconstructed 320 simulated radiographs from the CT scans of 40
      adult hips at different rotational projections of 10 degrees  increments from 30
      degrees  internal rotation to 40 degrees  external rotation. Underestimation of
      femoral offset as a percentage was derived from the neck profile angle for all
      radiographs. Radiographs with an LTI value above 35 were 94% (95% CI, 89%-97%)
      likely to underestimate femoral offset by more than 5%. Radiographs with LTI
      between 0 and 30 demonstrated femoral offset within 5% of the true offset
      (predictive value 100%, CI 87%-100%). LTI could be a useful guide in preoperative
      templating of hip arthroplasty. 

PMID- 24439752
TI  - Author reply: "correlation of aspiration results with periprosthetic sepsis in
      revision total hip arthroplasty".

PMID- 24439753
TI  - Gait parameters and muscle activation patterns at 3, 6 and 12 months after total
      hip arthroplasty.
AB  - Gait analysis was performed on 20 patients with unilateral hip prosthesis (3, 6
      and 12 months post-operatively) and 20 controls to investigate their gait
      characteristics and muscle activation patterns. One year after the intervention,
      patients still walked with a higher percentage of "atypical" cycles, a prolonged
      heel contact, a shortened flat foot contact, a reduced hip dynamic range of
      motion and abnormal timing in the muscle activation patterns of tibialis
      anterior, gastrocnemius lateralis, biceps femoris and gluteus medius, with
      respect to the control group. Although the gait velocity and the knee range of
      motion improved from 3 to 6 months post-surgery, the above mentioned parameters
      did not improve from 6 to 12 months. THA patients failed to obtain normal gait
      one year after surgery.

PMID- 24439754
TI  - Non-invasive induction of plasticity in the human cortex: uses and limitations.
AB  - The last couple of decades have seen the development of a number of non-invasive
      brain stimulation (NIBS) techniques that are capable of inducing short-lasting
      plasticity in the human cortex. Importantly, the induction of lasting plastic
      changes can, under some conditions, reversibly modify behaviour and interact with
      learning. These techniques have provided novel opportunities to study human
      cortical plasticity and examine the role of cortical regions in behaviour. In
      this review we briefly summarise current NIBS techniques, outline approaches to
      characterise and quantify cortical plastic change, and describe mechanisms that
      are implicated in the induced plastic changes. We then outline the areas in which
      these techniques might be useful, namely, investigating the mechanisms of human
      cortical plasticity, the characterisation of influences on plasticity, and the
      investigation of the role of cortical regions in behaviour. Finally, we conclude
      by highlighting some current limitations of the techniques and suggest that
      further development of the current NIBS paradigms and more focussed targeting
      should further enhance the utility of these powerful non-invasive techniques for
      the investigation of the cortical plasticity and pathophysiology. 

PMID- 24439755
TI  - The antidepressant drug carbamazepine induces differential transcriptome
      expression in the brain of Atlantic salmon, Salmo salar.
AB  - Concerns are being expressed recently over possible environmental effects of
      human pharmaceuticals. Although the likelihood of acute toxicity is low, the
      continuous discharge of pharmaceuticals into the aquatic environment means that
      sublethal effects on non-target organisms need to be seriously considered. One
      year-old Atlantic salmon parr were exposed to 7.85+/-0.13MUgL(-1) of the
      antidepressant drug Carbamazepine (CBZ) for five days to investigate changes of
      mRNA expression in the brain by means of a custom 17k Atlantic salmon cDNA
      microarray. The selected concentration is similar to upper levels that can be
      found in hospital and sewage treatment plant effluents. After treatment, 373
      features were differently expressed with 26 showing up- or down-regulation of >=2
      fold (p<=0.05). Among the mRNAs showing the highest change were the pituitary
      hormones encoding features somatolactin, prolactin and somatotropin, or growth
      hormone. Functional enrichment and network analyses of up- and down-regulated
      genes showed that CBZ induced a highly different gene expression profile in
      comparison to untreated organisms. CBZ induced expression of essential genes of
      the focal adhesion and extracellular matrix - receptor interaction pathways most
      likely through integrin alpha-6 (itga6) activation. Negative regulation of
      apoptotic process, extracellular matrix organization and heme biosynthesis were
      the most enriched biological process related GO-terms, with the simultaneous
      enrichment of collagen and extracellular region related cellular component GO
      terms, and extracellular matrix structural constituent, hormone activity and
      chromatin binding molecular function related GO-terms. These results show that
      relatively low doses of CBZ may affect brain physiology in exposed salmon parr,
      targeting similar processes as in human, indicating a high degree of conservation
      of targets of CBZ action. However, and since the mRNAs showing most changes in
      expression are critical for adaptation to different stressors and life history
      transitions in Atlantic salmon, more research should be undertaken to assess CBZ
      effects to avoid impairment of normal development and maintenance of natural
      populations. 

PMID- 24439756
TI  - Network of telocytes in the temporomandibular joint disc of rats.
AB  - The phenotypes of the temporomandibular joint (TMJ) disc cells range from
      fibroblasts to chondrocytes. There are relatively few reported studies using
      transmission electron microscopy (TEM) to determine the ultrastructural features
      of these cells. It was hypothesized that at least a subpopulation of TMJ stromal
      cells could be represented by the telocytes, cells with telopodes. In this regard
      a TEM study was performed on rat TMJ samples. Collagen-embedded networks were
      found built-up by cells with telopodes with subplasmalemmal caveolae, moderate
      content in matrix secretory organelles and well-represented intermediate
      filaments. Appositions of cell bodies were found. Prolongations of such cells
      were closely related to nerves and microvessels. Our study indicates that the TMJ
      disc attachment seems equipped with telocytes capable of stromal signaling.
      However, further studies are needed to assess whether the telocytes belong to a
      renewed cell population derived from circulating precursors.

PMID- 24439757
TI  - Clinical and spectral-domain optical coherence tomography findings in patients
      with focal choroidal excavation.
AB  - OBJECTIVE: To describe the clinical and spectral-domain optical coherence
      tomography (SD-OCT) findings in patients with focal choroidal excavation (FCE).
      DESIGN: Retrospective case series. PARTICIPANTS: Forty-one eyes of 38 patients
      with FCE identified in 2 tertiary medical centers in Korea. METHODS: Clinical
      features, SD-OCT findings, and associated macular disorders of FCE were analyzed
      and detailed. MAIN OUTCOME MEASURES: Statistical associations among clinical
      features, including lesion type, size, and choroidal thickness, and frequency of
      association with central serous chorioretinopathy (CSC), choroidal
      neovascularization (CNV), and polypoidal choroidal vasculopathy (PCV). RESULTS:
      Mean patient age was 50.1 years (range, 25-76 years). The mean spherical
      equivalent of refractive error was -3.7 diopters (range, -10.0 to +1.5 diopters).
      Three patients (8%) had bilateral lesions, and 1 patient (3%) had 2 distinct
      lesions in the same eye. The mean FCE width and depth were 757 MUm and 107 MUm,
      respectively, with a positive correlation between width and depth (P = 0.003).
      The mean subfoveal choroidal thickness of FCE eyes was 284 MUm, which was not
      statistically different from that of age-, sex-, and refractive error-matched
      normal subjects. Choroidal thickness in FCE was less in eyes with hyperreflective
      choroidal tissue under the excavation that was present in 22 eyes (54%) versus
      eyes without excavation (128 vs. 190 MUm, respectively; P = 0.009). Twelve FCEs
      (29%) were the nonconforming type, revealing separation between the photoreceptor
      tips and the retinal pigment epithelium on SD-OCT. Nonconforming FCE was
      associated with visual symptoms (P < 0.001) and the presence of concurrent CSC (P
      = 0.001). Ten eyes (24%) were associated with CSC, and 9 eyes (22%) were
      associated with CNV, including 1 eye with PCV features. One eye with FCE and type
      1 CNV developed a new excavation, and the excavated area in 1 eye with PCV
      enlarged slightly during follow-up. CONCLUSIONS: Focal choroidal excavation is a
      relatively common entity and frequently associated with choroidal diseases,
      including CSC, CNV, and PCV. Although FCE is classically thought to be a
      congenital malformation, acquired FCE forms possibly exist.

PMID- 24439759
TI  - Disparity between visual fields and optical coherence tomography in
      hydroxychloroquine retinopathy.
AB  - PURPOSE: American Academy of Ophthalmology recommendations for screening for
      hydroxychloroquine (HCQ) retinopathy advise objective measures, such as spectral
      domain optical coherence tomography (SD-OCT) and multifocal electroretinography
      (mfERG) along with visual fields. However, the relative sensitivity and
      specificity of screening tests have not been fully resolved. We characterize a
      subset of patients with toxicity who show unusual disparity between fields and SD
      OCT and thus have implications for screening practice. DESIGN: Review of charts
      and clinical data. PARTICIPANTS: Patients at Stanford and Kaiser Permanente who
      had used HCQ with greater than 1000 g cumulative exposure. There were more than
      2000 such individuals, among whom 150 had clear evidence of toxicity. METHODS:
      Patients were evaluated by visual fields (10-2 white Swedish Interactive
      Threshold Algorithm pattern deviation plots), SD-OCT, and sometimes mfERG or
      fundus autofluorescence. MAIN OUTCOME MEASURES: Relative findings on visual
      fields in comparison with SD-OCT. RESULTS: There were 11 patients among those
      with HCQ toxicity who had parafoveal ring scotomas but a normal-appearing SD-OCT.
      None had a history of macular disease or evidence for any other cause of bull's
      eye maculopathy. Conversely, all cases with a clear degree of parafoveal damage
      on SD-OCT showed at least some focal spots of parafoveal field loss. CONCLUSIONS:
      Approximately 10% of patients with early HCQ toxicity showed prominent ring
      scotomas on field testing without obvious SD-OCT abnormality. This should
      encourage the inclusion of visual fields as a key screening tool, even when SD
      OCT (a more specific and objective test) also is performed. The combination of
      visual fields and SD-OCT gives both sensitivity and specificity while avoiding
      unnecessary stoppage of the drug.

PMID- 24439758
TI  - Collaborative retrospective macula society study of photodynamic therapy for
      chronic central serous chorioretinopathy.
AB  - PURPOSE: To assess the visual and anatomic outcomes of central serous
      chorioretinopathy (CSC) after verteporfin photodynamic therapy (PDT). DESIGN:
      Retrospective case series. PARTICIPANTS: Patients with CSC who underwent PDT.
      METHODS: Members of the Macula Society were surveyed to retrospectively collect
      data on PDT treatment for CSC. Patient demographic information, PDT treatment
      parameters, fluorescein angiographic information, optical coherence tomography
      (OCT) metrics, pre- and post-treatment visual acuity (VA), and adverse outcomes
      were collected online using standardized forms. MAIN OUTCOME MEASURES: Visual
      acuities over time and presence or absence of subretinal fluid (SRF). RESULTS:
      Data were submitted on 265 eyes of 237 patients with CSC with a mean age of 52
      (standard deviation [+/- 11]) years; 61 were women (26%). Mean baseline logarithm
      of the minimum angle of resolution (logMAR) VA was 0.39+/-0.36 (20/50). Baseline
      VAs were >=20/32 in 115 eyes (43%), 20/40 to 20/80 in 97 eyes (37%), and <=20/100
      in 47 eyes (18%). Normal fluence was used for PDT treatment in 130 treatments
      (49%), half-fluence was used in 128 treatments (48%), and very low fluence or
      missing information was used in 7 treatments (3%). The number of PDT treatments
      was 1 in 89%, 2 in 7%, and 3 in 3% of eyes. Post-PDT follow-up ranged from 1
      month to more than 1 year. Post-PDT VA was correlated with baseline VA (r = 0.70,
      P < 0.001). Visual acuity improved >=3 lines in <1%, 29%, and 48% of eyes with
      baseline VA >=20/32, 20/40 to 20/80, and <=20/100, respectively. Subretinal fluid
      resolved in 81% by the last post-PDT visit. There was no difference in the
      response to PDT when analyzed by age, race, fluence setting, fluorescein
      angiography (FA) leakage type, corticosteroid exposure, or fluid location
      (subretinal or pigment epithelial detachment; all P > 0.01). Complications were
      rare: Retinal pigment epithelial atrophy was seen in 4% of patients, and acute
      severe visual decrease was seen in 1.5% of patients. CONCLUSIONS: Photodynamic
      therapy was associated with improved VA and resolution of SRF. Adverse side
      effects were rare.

PMID- 24439760
TI  - Histopathology of streptococcus mitis/oralis endophthalmitis after intravitreal
      injection with bevacizumab: a report of 7 patients.
AB  - PURPOSE: To report the histopathologic findings of a series of patients from an
      outbreak of Streptococcal endophthalmitis after intravitreal injection of
      bevacizumab prepared by a single compounding pharmacy. DESIGN: Case series.
      PARTICIPANTS: Seven surgical specimens (5 enucleated globes and 2 evisceration
      specimens) from 7 patients with endophthalmitis after intravitreal injection of
      bevacizumab. METHODS: Retrospective case series, including clinical data and
      histopathologic specimens examined by light microscopy. MAIN OUTCOME MEASURES:
      Review of clinical data included baseline visual acuity, clinical intervention,
      and time elapsed from injection to loss of globe. Histopathologic specimens were
      reviewed for pathologic changes at all tissue levels. RESULTS: Seven of 12 total
      patients (4 women, 3 men; mean age, 77.7 years) from an outbreak of Streptococcus
      mitis/oralis endophthalmitis after bevacizumab injection ultimately sustained
      loss of the affected globe, with an average of 139.1 days elapsed between
      injection and globe loss. Mean time from injection to presentation was 2.86 days
      (range, 1-6), and all patients were initially treated with vitreous tap and
      injection. Although histologic review of surgical specimens disclosed a wide
      range of pathologic tissue changes, recurring patterns of tissue damage were
      evident. All 5 enucleated globes displayed retinal detachment, fibrous
      proliferation with cyclitic membrane formation, rubeosis iridis, and secondary
      angle closure. All 7 specimens displayed persistent choroidal inflammation, in 1
      case 208 days after injection. Six of 7 specimens had foci of retinal necrosis.
      Although vitreous cultures were positive in all cases, no organisms were
      identified by light microscopy in any of the 7 specimens. CONCLUSIONS: S.
      mitis/oralis endophthalmitis is a devastating complication of intravitreal
      injection with bevacizumab with a high rate of globe loss (7 of 12 patients,
      58.3%) and a wide variety of severe pathologic tissue changes. Although no
      organisms were identified in the examined tissues, persistent inflammation was
      present in all cases, and fibrous proliferation resulted in cyclitic membrane
      formation and retinal detachment in all enucleated globes. These findings suggest
      that potential globe-salvaging interventions must address a pattern of changes
      involving persistent, chronic inflammation and fibrovascular proliferation as key
      components.

PMID- 24439761
TI  - Computational and mathematical modeling of the effects of tailbeat frequency and
      flexural stiffness in swimming fish.
AB  - In this paper we describe how we combine computational and mathematical models to
      form virtual fish to explore different hypotheses about the impact of centra. We
      show how we create simulation models using a combination of a mathematical model
      of a fish-like robot using caudal fin propulsion, a propulsion model, and an
      optimizer, to explore the impact of centra under various scenarios. The optimizer
      uses the mathematical model to construct valid configurations of the digital
      robot and uses the utility function and propulsion model to evaluate the
      performance of each configuration. The evaluations are used to explore the
      adaptive landscape and find high-performing configurations. Our results show that
      the high-performing configurations have both increased (flexural) stiffness of
      the tail and higher tailbeat frequencies. 

PMID- 24439762
TI  - Influence of receptor activator of nuclear factor kappa B ligand, osteoprotegerin
      and interleukin-33 on bone metabolism in patients with long-standing ulcerative
      colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) is a chronic disease with periods of
      remission and recurrences. Dysfunction of the local immune response leads to
      chronic inflammation within the large intestine which triggers morphological
      changes in the intestinal wall as well as induces the synthesis of numerous
      factors that have an adverse impact on the bone metabolism. The aim of the study
      was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC
      patients with long disease duration as well as serum level of these cytokines in
      the context of bone density and bone metabolism. MATERIALS AND METHODS: The UC
      group consisted of 56 patients with average disease duration of 16y. The control
      group comprised 37 healthy individuals. Local expression of cytokines was
      assessed in the biopsies of colonic mucosa by the real-time PCR and
      immunohistochemistry (IHC), and their serum concentration was measured by ELISA.
      RESULTS: The increased bone resorption observed in patients with UC was reflected
      by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal
      RANKL expression and serum concentration were similar in UC group and healthy
      subjects, however, UC patients had higher local expression of OPG and serum OPG
      concentration. Increased IL-33 gene expression was observed only in UC at the
      mRNA level. We propose that bone resorption in UC patients despite OPG up
      regulation could be caused by IL-33-induced mucosal synthesis of a potent
      proinflammatory cytokine, such as TNF-alpha, known as a possible inducer of
      osteoclastogenesis in the way independent of RANKL.

PMID- 24439764
TI  - The knee. Editorial.

PMID- 24439763
TI  - Radiofrequency of the soft palate for sleep-disordered breathing: a 6-year follow
      up study.
AB  - OBJECTIVE: To determine the long-term (>3 years) outcome of patients suffering
      from simple snoring or non-severe obstructive sleep apnea syndrome (OSAS) treated
      by radiofrequency ablation of the soft palate. STUDY DESIGN: Observational
      retrospective study. SETTING: Tertiary care university hospital. SUBJECTS AND
      METHODS: Seventy-seven subjects were included between 1999 and 2006. Twenty-seven
      suffered from mild or moderate OSAS. All patients were treated by radiofrequency
      assisted stiffening of the soft palate, with or without uvulectomy. Snoring
      (assessed on a 10 cm visual analog scale (VAS)), marital status, presence of
      cardiovascular risk factors or pathologies and follow-up time were evaluated by
      postal questionnaire. RESULTS: Mean follow-up time was 6.3 +/- 2.3 years. Mean
      snoring intensity decreased significantly in the immediate postoperative period
      (8.1 +/- 2.9 to 3.5 +/- 2.2 cm on VAS). Over the longer term, however, we
      observed a significant increase in snoring intensity (5.7 +/- 2.9 cm), which
      nevertheless remained below the preoperative values (P<0.001). Bed-partners
      noticed a relapse of snoring in 92.7% of cases. Nine percent of couples
      separated. Hypertension and diabetes were diagnosed during follow-up in 12.1% and
      6.6% of the subjects, respectively. A majority of patients failed to undergo
      repeat polysomnography or further treatment. CONCLUSION: Relapse of snoring was
      observed in nearly all patients in the long run, although intensity appears to
      remain lower than preoperatively. Most patients did not comply with the follow-up
      instructions and did not seek other forms of treatment when recurrence occurred.

PMID- 24439765
TI  - Inherited knee disorders in the Medici family.
AB  - Reconstructing a medical condition which was existent centuries ago is limited by
      the lack of contemporaneous evidence-based descriptions in the accounts given by
      physicians and other observers. Despite these limitations modern
      paleopathological evidence, supplemented by techniques of historical
      investigation, have led to the conclusion that males in the Medici family
      typically suffered from a complex clinical entity with a triple pathology of
      stenotic spinal ankylosis, recurrent peripheral joint disease and erythematous
      skin disease; the Medici Syndrome. Examination of the knee joint is illustrative
      of recurrent joint disease both in the primary and secondary lines of the family.
      Pictorial and sculptural representations, if used cautiously, can assist in this
      retrospective process. The six cases presented here illustrate the involvement of
      the knee joint where the joint destruction ultimately led to an ankylosis. 

PMID- 24439766
TI  - Story of my passion.

PMID- 24439767
TI  - Towards radiological diagnosis of abdominal adhesions based on motion signatures
      derived from sequences of cine-MRI images.
AB  - This paper reports novel development and preliminary application of an image
      registration technique for diagnosis of abdominal adhesions imaged with cine-MRI
      (cMRI). Adhesions can severely compromise the movement and physiological function
      of the abdominal contents, and their presence is difficult to detect. The image
      registration approach presented here is designed to expose anomalies in movement
      of the abdominal organs, providing a movement signature that is indicative of
      underlying structural abnormalities. Validation of the technique was performed
      using structurally based in vitro and in silico models, supported with Receiver
      Operating Characteristic (ROC) methods. For the more challenging cases presented
      to the small cohort of 4 observers, the AUC (area under curve) improved from a
      mean value of 0.67 +/- 0.02 (without image registration assistance) to a value of
      0.87 +/- 0.02 when image registration support was included. Also, in these cases,
      a reduction in time to diagnosis was observed, decreasing by between 20% and 50%.
      These results provided sufficient confidence to apply the image registration
      diagnostic protocol to sample magnetic resonance imaging data from healthy
      volunteers as well as a patient suffering from encapsulating peritoneal sclerosis
      (an extreme form of adhesions) where immobilization of the gut by cocooning of
      the small bowel is observed. The results as a whole support the hypothesis that
      movement analysis using image registration offers a possible method for detecting
      underlying structural anomalies and encourages further investigation. 

PMID- 24439768
TI  - Cytokine expression at the anchor site in experimental Taenia solium infection in
      hamsters.
AB  - The establishment of Taenia solium adult parasite in the human intestine causes
      taeniosis. Importantly, the immunological mechanisms occurring at the interface
      between the parasite and its host are not fully known. The development of
      experimental animal models has facilitated the understanding of the host-parasite
      relationship. In this study we standardized a quantitative RT-PCR method for
      analyzing hamster messenger RNA for interferon-gamma (IFN-gamma) and interleukins
      (IL): IL-4 IL-10, IL-12 and IL-13. This method was then used to evaluate the
      local cytokine response elicited against the adult parasite at the attachment
      site in the intestine of infected hamsters. The results showed an intense IFN
      gamma response, as well as an up-regulation of IL-4 as early as three days post
      infection, permanence of IL-10 until the end of the experiment and down
      regulation of IL-12. These data are in agreement with a bias toward a Th-2
      response as the infection progresses. 

PMID- 24439769
TI  - Failure of imidocarb dipropionate and toltrazuril/emodepside plus clindamycin in
      treating Hepatozoon canis infection.
AB  - Hepatozoonosis caused by Hepatozoon canis (Eucoccidiorida, Hepatozoidae) is among
      the most widespread vector-borne infections of dogs, primarily transmitted by
      Rhipicephalus sanguineus sensu lato ticks. Based on the absence of a consensus on
      the treatment regimes for canine hepatozoonosis, the present study aimed to
      evaluate the efficacy of imidocarb dipropionate (5-6 mg/kg subcutaneously once a
      week for 6 weeks), and of toltrazuril/emodepside (Procox((r)), 15 mg/kg once a
      day for 6 days) in association with clindamycin (15 mg/kg once a day for 21 days)
      in treating naturally infected dogs. At the enrollment time (T0), 32 dogs,
      cytologically or molecularly positive for H. canis, were assigned to test and
      control groups. Animals were treated according to the specific therapeutic
      protocol, and the presence of H. canis gamonts was assessed weekly by cytology
      and PCR throughout six months (T1-T19). In addition, any abnormality in leucocyte
      morphology was evaluated and recorded. Results indicate that, in spite of a
      reduction in the percentage of infected dogs, both treatments did not provide
      parasitological cure. Accordingly, new treatment protocols or active compounds
      against H. canis should be investigated.

PMID- 24439770
TI  - Herding the U.S. cattle industry toward a paradigm shift in parasite control.
AB  - Contemporary management of nematode parasitism in cattle relies heavily on a
      single class of drugs, the macrocyclic lactones (MLs). The potency and
      convenience of the MLs, along with the low cost of generic formulations, have
      largely supplanted the need for critical thinking about parasite control, and
      rote treatment has become the default 'strategy'. This approach to parasite
      control has exerted substantial pressure to select populations of nematodes that
      can survive recommended dosages of ML products. Although macrocyclic lactones
      have been available for over 30 years, putative ML resistance in U.S. cattle was
      not reported until fairly recently. This pattern begs the question, "Is this a
      new, emergent problem, or an old issue that is finally commanding some
      attention?" The implications of bovine anthelmintic resistance should stimulate a
      paradigm shift for U.S. cattle producers and their advisors. However, there are
      significant obstacles to changes in current thinking. It is anticipated that
      cattle producers will be extremely reluctant to abandon historical practices
      unless they can be convinced of the value of alternatives that are communicated
      through targeted education, practical demonstrations, economic analyses, and
      scientific evidence. Historically, the management advice of practitioners has not
      relied strongly on parasite epidemiology, and practitioners may not have the
      knowledge to implement evidence-based recommendations. Pharmaceutical companies
      could play a significant role in helping to shape and shift the thinking about
      sustainable use of anthelmintics. However, their primary responsibility is to
      stockholders, and they have strong economic incentives for maintaining the status
      quo. It is complicated and difficult to change attitudes and practices, and it
      will take more than logic or fear to shift the parasite control paradigm in the
      U.S. cattle industry. Achieving that goal will require collaboration among
      stakeholders, a consistent, straightforward and understandable message about
      resistance, and recommendations that are practical as well as effective. But if
      we hope to ultimately influence producers and their advisors, we need to be
      conscious of how individuals and groups change their minds. 

PMID- 24439771
TI  - Visceral leishmaniasis in zoo and wildlife.
AB  - Visceral leishmaniasis (VL) is an emerging zoonosis caused by Leishmania
      (Leishmania) infantum. Although the domestic dog is the main vertebrate host,
      many zoo and wild mammal species have been diagnosed with L. infantum infection,
      especially in endemic areas. There are many available diagnostic approaches,
      including serological, parasitological and molecular tests. Among wild animals,
      carnivores and primates are more often clinically affected, with some species,
      such as the bush dog (Speothos venaticus) being especially susceptible to
      development of clinical signs. There are also reports and research articles of VL
      in felids, rodents, and marsupials. This work aims to review the occurrence of VL
      in zoo and wildlife and raise awareness of its importance in the field of
      conservational veterinary medicine. 

PMID- 24439772
TI  - Prognostic factors of heart failure with preserved ejection fraction: a 12-year
      prospective cohort follow-up study.
AB  - BACKGROUND: Although heart failure with preserved ejection fraction (HFpEF) is a
      clinically important issue, the factors that affect its prognosis are still
      unclear. The aim of this study was to establish prognostic factors and develop a
      severity scale for the disease based on a long-term follow-up cohort of HFpEF
      patients. METHODS: The study included 438 HFpEF patients, as confirmed via
      echocardiography. Baseline characteristics, including echocardiographic findings
      and genetic polymorphisms, were determined. Patients were followed-up for up to
      12 years. Kaplan-Meier curves and Cox regression models were used to determine
      the risk factors for mortality and major cardiovascular events (MACE). A severity
      scale was established using the significant risk factors. The receiver operating
      characteristics (ROC) curves for the scale were plotted. RESULTS: The
      prescription of angiotensin-converting enzyme (ACE) inhibitors [hazard ratio (HR)
      0.28; 95% confidence interval (CI): 0.13-0.58 for mortality] and calcium channel
      blockers (CCB) was associated with a significant decrease in overall mortality
      and MACE. Echocardiographic E/Em ratio and ACE gene D polymorphisms were powerful
      factors associated with both mortality and MACE [(E/Em; HR 1.66; 95% CI: 1.32
      2.29 for mortality) and (ACE gene D allele, HR 1.99; 95% CI: 1.26-3.16 for
      mortality)]. The ROC curves indicated a good diagnostic efficiency for severity
      scores (area under the curve 0.72). CONCLUSIONS: In a long-term follow-up cohort
      of HFpEF patients, simple clinical, echocardiographic, medication, and even
      genetic variables were associated with MACE or mortality, and the developed
      composite severity scale identified patients with a higher probability of
      experiencing the events.

PMID- 24439774
TI  - Darwin and the patent foramen ovale phenotype.

PMID- 24439773
TI  - DNA aptamer raised against advanced glycation end products inhibits neointimal
      hyperplasia in balloon-injured rat carotid arteries.
AB  - BACKGROUND: Advanced glycation end products (AGE) and their receptor (RAGE)
      interaction elicit inflammatory and proliferative reactions in arteries, thus
      playing a role in cardiovascular disease. We have recently found that high
      affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression
      of experimental diabetic nephropathy by blocking the harmful actions of AGEs in
      the kidney. However, effects of AGE-aptamer on vascular injury remain unknown. In
      this study, we examined whether and how AGE-aptamer inhibits neointimal
      hyperplasia in balloon-injured rat carotid arteries. METHODS: Male Wistar rats
      (weighting ca. 400 g at 11 weeks old) were anesthetized with sodium
      pentobarbital. The left common carotid artery was balloon-injured 3 times with 2F
      Fogaty catheter inserted through the femoral artery. Then the rats received
      continuous intraperitoneal infusion (3 MUg/day) of either AGE-aptamer or control
      aptamer by an osmotic mini pump for 2 weeks. 14 days after the procedure, the
      left common carotid arteries were excised for morphometric, immunohistochemical
      and western blot analyses. RESULTS: Compared with control-aptamer, AGE-aptamer
      significantly suppressed neointima formation after balloon injury and reduced AGE
      accumulation, oxidative stress generation, proliferation cell nuclear antigen
      positive area, macrophage infiltration, RAGE and platelet-derived growth factor
      BB (PDGF-BB) expression levels in balloon-injured carotid arteries. CONCLUSION:
      The present study suggests that AGE-aptamer could prevent balloon injury-induced
      neointimal hyperplasia by reducing PDGF-BB and macrophage infiltration via
      suppression of the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer
      might be a novel therapeutic strategy for suppressing neointima formation after
      balloon angioplasty.

PMID- 24439775
TI  - Increased ventricular wall stress and late gadolinium enhancement in Takotsubo
      cardiomyopathy.

PMID- 24439776
TI  - Feasibility of transradial coronary intervention in patients with cardiac arrest
      caused by acute coronary syndrome.

PMID- 24439777
TI  - Diagnostic power of echocardiographic speckle tracking of the tricuspid annular
      motion to assess right ventricular dysfunction.

PMID- 24439778
TI  - Formation of the inflammasome in acute myocarditis.

PMID- 24439779
TI  - Neurohormones, cytokines, and aortic function in children with repaired
      coarctation of the aorta.

PMID- 24439780
TI  - Computer-assisted diagnosis of obstructive coronary atherosclerosis in patients
      undergoing 256-slice coronary computed tomography angiography: a comparison with
      invasive coronary angiography.

PMID- 24439781
TI  - In response to Pormate Pitak-Arnnop's commentary, "is radiotherapy necessary for
      pleomorphic adenoma?".

PMID- 24439782
TI  - The role of sentinel lymph node biopsy for thin cutaneous melanomas of the head
      and neck.
AB  - From 18% to 35% of cutaneous melanomas are located in the head and neck, and
      nearly 70% are thin (Breslow thickness <= 1 mm). Sentinel lymph node biopsy
      (SLNB) has an established role in staging of intermediate-thickness melanomas,
      however its use in thin melanomas remains controversial. In this article, we
      review the literature regarding risk factors for occult nodal metastasis in thin
      cutaneous melanoma of the head and neck (CMHN). Based on the current literature,
      we recommend SLNB for all lesions with Breslow thickness >= 0.75 mm, particularly
      when accompanied by adverse features including mitotic rate >= 1 per mm(2),
      ulceration, and extensive regression. SLNB should also be strongly considered in
      younger patients (e.g. < 40 years old), especially in the presence of additional
      adverse features. All patients who do not proceed with sentinel lymph node biopsy
      must be carefully followed to monitor for regional relapse.

PMID- 24439783
TI  - Malignancies: pre and post transplantation strategies.
AB  - The overall incidence of cancer is increased 2-3 fold in solid organ transplant
      recipients compared to the general population. The increase in risk is not
      uniform for all malignancies, in all ages or in all regions of the world. Several
      cancers are greatly increased, many are increased 2-4 fold and others do not
      appear to be increased at all. The pattern of increase is similar to patients
      with acquired immunodeficiency syndrome and those cancers most increased are
      associated with viral infections. These observations support the concept that
      much of the increased risk is from immunosuppression. Nonetheless there are
      differences between specific organ groups that deserve further examination. Those
      with advanced organ failure are also at increased risk for certain malignancies,
      which suggest either organ damage per se may pre-dispose to cancers or there are
      exposures to carcinogens in common. The purpose of this review to examine cancer
      incidence and mortality in solid organ transplantation and the role of pre
      transplant screening and post-transplant surveillance to reduce the burden of
      disease and improve patient outcomes. This review will focus on cancers that are
      common, associated with significant case fatality rates and have potential
      screening strategies to reduce burden of disease. 

PMID- 24439784
TI  - Characterization of right wrist posture during simulated colonoscopy: an
      application of kinematic analysis to the study of endoscopic maneuvers.
AB  - BACKGROUND: Endoscopic maneuvers are associated with a high incidence of
      musculoskeletal injuries. OBJECTIVE: To quantify wrist motion patterns during
      simulated endoscopic procedures to identify potential causes of endoscopy-related
      overuse injury. DESIGN: Twelve endoscopists with different levels of experience
      were tested on 2 simulated endoscopic procedures that differed in their level of
      difficulty. SETTING: Right wrist movement patterns were recorded during simulated
      colonoscopies by using a magnetic motion-tracking device. Analysis focused on 3
      wrist degrees of freedom: abduction/adduction, flexion/extension, and
      pronation/supination. INTERVENTIONS: Subjects were tested on 2 GI lower
      endoscopies (colonoscopies) on a simulator. MAIN OUTCOME MEASUREMENTS: Time spent
      within ranges of the entire wrist range of motion for 3 wrist degrees of freedom.
      RESULTS: Endoscopists spent up to 30% of the duration of the procedures at the
      extremes of the wrist joint range of motion. Endoscopic experience did not affect
      the time spent at the extremes of the wrist joint of motion. The time spent
      within each range of motion differed depending on the wrist degrees of freedom
      and difficulty of procedure. LIMITATIONS: This study examined only 1 upper limb
      joint in a limited number of subjects and did not measure interaction forces with
      endoscopic tools. CONCLUSIONS: We identified wrist movement patterns that can
      potentially contribute to the occurrence of musculoskeletal injury in
      endoscopists. This study lays the foundation for future work on establishing
      links between upper limb movement patterns and the occurrence of overuse injury
      caused by repetitive performance of endoscopic procedures.

PMID- 24439786
TI  - Toremifene for breast cancer: a review of 20 years of data.
AB  - Endocrine therapy is a cornerstone of medical treatment for estrogen receptor
      positive breast cancer. The discovery of selective estrogen receptor modulators
      (SERMs) > 40 years ago represented a revolutionary advance in the treatment of
      breast cancer. As a therapeutic class, SERMs have either estrogenic or
      antiestrogenic activity, depending on the target tissue and the hormonal
      environment. In breast tissue, SERMs are antiestrogenic, making them a major
      treatment option for women with hormone-sensitive breast cancer. Toremifene
      citrate was developed > 20 years ago with the goal of achieving efficacy similar
      to that of tamoxifen and with an improved safety profile. Although studies to
      date have not confirmed a clear safety advantage or disadvantage for toremifene,
      clinical data support the efficacy and safety of toremifene for the treatment of
      breast cancer in postmenopausal patients. Toremifene also has a pharmacokinetic
      profile and metabolic pathway different from that of tamoxifen, which may provide
      a therapeutic advantage in certain patients. In addition, because of the
      selective estrogenic effects of SERMs in bone and on lipid levels along with a
      different side effect profile compared with the aromatase inhibitors (AIs),
      toremifene is a viable option to the AIs for some patients. Despite a number of
      clinical trials and over 500,000 patient years of use, many oncologists have
      limited familiarity with toremifene data. This article will examine the rationale
      for the use of toremifene in the treatment of women with breast cancer and review
      data from 20 years of clinical experience with this agent. 

PMID- 24439789
TI  - [A storm is brewing around the DSM V (the new anti-psychiatry)].

PMID- 24439790
TI  - [Written information for patients: From papers to documents].
AB  - INTRODUCTION: There is a high variability in the level of information intended
      for patients, with different content, format and presentation. OBJECTIVE: To
      determine the perceived safety of the patients treated at the Country Hospital of
      Melilla (HCML) and to assess the quality of the documents using criteria adapted
      to the "International Patient Decision Aid Standards" (IPDAS). METHOD:
      Descriptive study of the documents given to patients by the HCML. They included
      questionnaires on perceived safety, classification of the documents, and the
      level of adherence to the IPDAS criteria. RESULTS: The Information given to
      patients during their stay in the HCML, their participation in decision-making,
      and the information about medication, did not exceed the average on the
      acceptance scale. Only 40 documents were studied (of the 131 collected), on being
      published in-house, and were classified, following the definitions of the RAE,
      into instructions (20), recommendations (14) and guidelines (6). Of these, only
      the 27.5% showed hospital logo. In the content analysis according to the IPDAS
      criteria, there was an overall adherence rate of 24.1% in instructions, 24.8% in
      recommendations, and 61.5% in guidelines. CONCLUSIONS: The perception of patient
      safety expressed in the questionnaire, and its assessment according IPDAS
      criteria, shows there may be a significant improvement within the organization.
      Furthermore, the quality of patient documentation provided can help decision
      making.

PMID- 24439788
TI  - Overdiagnosis and overtreatment of prostate cancer.
AB  - CONTEXT: Although prostate cancer (PCa) screening reduces the incidence of
      advanced disease and mortality, trade-offs include overdiagnosis and resultant
      overtreatment. OBJECTIVE: To review primary data on PCa overdiagnosis and
      overtreatment. EVIDENCE ACQUISITION: Electronic searches were conducted in
      Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception
      to July 2013 for original articles on PCa overdiagnosis and overtreatment.
      Supplemental articles were identified through hand searches. EVIDENCE SYNTHESIS:
      The lead-time and excess-incidence approaches are the main ways used to estimate
      overdiagnosis in epidemiological studies, with estimates varying widely. The
      estimated number of PCa cases needed to be diagnosed to save a life has ranged
      from 48 down to 5 with increasing follow-up. In clinical studies, generally lower
      rates of overdiagnosis have been reported based on the frequency of low-grade
      minimal tumors at radical prostatectomy (1.7-46.8%). Autopsy studies have
      reported PCa in 18.5-38.5%, although not all are low grade or low volume. Factors
      influencing overdiagnosis include the study population, screening protocol, and
      background incidence, limiting generalizability between settings. Reported rates
      of overtreatment vary widely in the literature, although contemporary
      international studies suggest increasing use of conservative management.
      CONCLUSIONS: Epidemiological, clinical, and autopsy studies have been used to
      examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%.
      Correspondingly, estimates of overtreatment vary widely based on patient features
      and may be declining internationally. Careful patient selection for screening and
      reducing overtreatment are important to preserve the benefits and reduce the
      downstream harms of prostate-specific antigen testing. Because all of these
      estimates are extremely population and context specific, this must be considered
      when using these data to inform policy. PATIENT SUMMARY: Screening reduces spread
      and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that
      may not have caused harm. Because treatment has potential side effects, it is
      critical that not all patients with PCa receive aggressive treatment.

PMID- 24439791
TI  - [Telemedicine in primary health care: How it affects professionals].

PMID- 24439792
TI  - Whirling disease dynamics: an analysis of intervention strategies.
AB  - Whirling disease (WD), a severe and widespread disease of salmonids, is caused by
      the myxosporean parasite Myxobolus cerebralis. It is further characterized by a
      unique two-host life cycle, utilizing the oligochaete Tubifex tubifex as an
      intermediate host. M. cerebralis is an invasive species that has been affecting
      populations in the United States including epidemics that killed in excess of 90%
      of populations in Colorado and Montana streams within the past 20 years.
      Currently, there is no known cure for WD, and the accepted method of control is
      removal of infected fish from the population. We have created a compartmental
      model of the WD system in order to assess more efficient means of control and
      management of the disease. Using data gathered from the literature, we used
      Bayesian model fitting to estimate model parameters and estimated that R0~1.51
      (95% CI: 1.39, 1.72), a value which implies that WD can be controlled using
      available strategies. To this end, we posit several parameters that we expect to
      be most influential to WD propagation, namely: release of triactinomyxons by T.
      tubifex, release of spores by salmonids, and infectious particle loads in each
      respective host. Based on currently available control strategies, approaches
      targeting the infectious particles and the oligochaete host appear the most
      effective alternative strategies for management and control of WD. 

PMID- 24439794
TI  - Editorial comment.

PMID- 24439795
TI  - Variations in the open market costs for prostate cancer surgery: a survey of US
      hospitals.
AB  - OBJECTIVE: To examine variation in the open market cost of a radical
      prostatectomy (RP) procedure in the US hospitals for an uninsured patient, as
      many proposals for health care reform highlight the importance of individuals
      actively participating in selecting care. However, reports suggest that obtaining
      procedure prices remains challenging and highly variable. MATERIALS AND METHODS:
      We used 2011-2012 US News and World Report rankings to identify a cohort of 100
      hospitals making an effort to include an equal distribution of both academic and
      private centers, city size, and geographic region. Each hospital was called and
      the essence of the script included a caller stating he was a healthy, uninsured
      55-year-old man recently diagnosed with Gleason 3 + 4 prostatic adenocarcinoma
      with no metastases. Facility, surgeon, and anesthesia fees were solicited.
      RESULTS: Seventy hospitals provided facility prices. Facility estimates averaged
      $34,720 (+/-20,335; range, $10,100-$135,000), which was statistically higher at
      academics centers. No significant differences were seen by region, population, or
      hospital ranking. Surgeon and anesthesia fees were provided by 10%, averaging
      $8280 (+/-$4282; range, $4028-$18,720). Thirty-three hospitals provided
      discounted fees for prompt payment averaging 34% (+/-16%; range, 10%-80%).
      CONCLUSION: There is wide variation in pricing for RP, with higher rates found in
      academic centers. Wide variation in facility costs were observed, and nearly all
      were unable to provide surgeon and/or anesthesia fees. Currently, it appears to
      be unacceptably difficult for men with prostate cancer without insurance to
      obtain prices for an RP procedure.

PMID- 24439796
TI  - Robot-assisted total knee arthroplasty accurately restores the joint line and
      mechanical axis. A prospective randomised study.
AB  - Robot-assisted Total Knee Arthroplasty (TKA) improves the accuracy and precision
      of component implantation and mechanical axis (MA) alignment. Joint-line
      restoration in robot-assisted TKA is not widely described and joint-line
      deviation of>5mm results in mid-flexion instability and poor outcomes. We
      prospectively randomised 60 patients into two groups: 31 patients (robot
      assisted), 29 patients (conventional). No MA outliers (>+/-3 degrees  from
      neutral) or notching was noted in the robot-assisted group as compared with 19.4%
      (P=0.049) and 10.3% (P=0.238) respectively in the conventional group. The robot
      assisted group had 3.23% joint-line outliers (>5mm) as compared to 20.6% in the
      conventional group (P=0.049). Robot-assisted TKA produces similar short-term
      clinical outcomes when compared to conventional methods with reduction of MA
      alignment and joint-line deviation outliers. 

PMID- 24439797
TI  - Pulse lavage is inadequate at removal of biofilm from the surface of total knee
      arthroplasty materials.
AB  - In acute periprosthetic infection, irrigation and debridement with component
      retention has a high failure rate in some studies. We hypothesize that pulse
      lavage irrigation is ineffective at removing biofilm from total knee arthroplasty
      (TKA) components. Staphylococcus aureus biofilm mass and location was directly
      visualized on arthroplasty materials with a photon collection camera and laser
      scanning confocal microscopy. There was a substantial reduction in biofilm signal
      intensity, but the reduction was less than a ten-fold decrease. This suggests
      that irrigation needs to be further improved for the removal of biofilm mass
      below the necessary bioburden level to prevent recurrence of acute infection in
      total knee arthroplasty. 

PMID- 24439798
TI  - Pineal region tumors: Clinical symptoms and syndromes.
AB  - The present paper investigates the clinical picture and the different clinical
      signs that reveal pineal region tumors or appear during the course of the follow
      up. Biological malignancy and tumor extension determine the semiology and its
      setting up mode. Typical endocrine signs, dominated by abnormal puberty
      development, are frequently a part of the clinical scene. Bifocal or ectopic
      localization in the hypothalamic-pituitary region is accompanied by other
      endocrine signs such as ante- or post-pituitary insufficiencies which occur
      several months or even years after the first neurological signs appear. Due to a
      mass syndrome and obstructive hydrocephalus, intracranial hypertension signs are
      frequent but unspecific. A careful ophthalmologic examination is essential to
      search upward gaze paralysis and other signs of the Parinaud's tetrad or pentad.
      Midbrain dysfunction, including extrinsic aqueduct stenosis, are also prevalent.
      Except for abnormal pubertal signs, hyper-melatoninemia (secretory tumors) or a
      hypo-melatoninemia (tumors destructing pineal) generally remains dormant. Some
      patients present sleep problems such as narcolepsy or sleepiness during the
      daytime as well as behavioral problems. This suggests a hypothalamic extension
      rather than a true consequence of melatonin secretion anomalies. Similarly, some
      patients may present signs of a "pinealectomized" syndrome, including (cluster)
      headaches, tiredness, eventually responsive to melatonin. 

PMID- 24439799
TI  - [The strange abscopal effect].

PMID- 24439800
TI  - [Obesity and coronary artery disease. Complex or paradox association?].

PMID- 24439801
TI  - Mechanisms of pluripotency in vivo and in vitro.
AB  - During the course of preimplantation development, the mammalian embryo develops
      from a single totipotent cell into a blastocyst that is composed of three
      distinct cell types. Two waves of lineage specification events take place,
      setting aside a pluripotent cell population, the epiblast, from extraembryonic
      tissues. The epiblast that will form the somatic cells and germ line of the adult
      organism remains pluripotent until gastrulation, which commences shortly after
      the embryo implants. The epiblast's remarkable property of pluripotency has been
      harnessed by researchers for decades through derivation of embryonic stem cells
      and epiblast stem cells. Both types of cells can self-renew indefinitely and
      still retain the ability of germ layer differentiation. However, a central
      conundrum to the field of stem cell biology is the extent to which these in vitro
      cultured cells represent their in vivo tissue of origin. In this review we
      discuss the development of in vivo pluripotency, and compare and contrast the
      role of signaling pathways and downstream transcription factors in embryo-derived
      stem cell types and their in vivo equivalent lineage counterparts. 

PMID- 24439802
TI  - Hematopoietic stem cell development: an epigenetic journey.
AB  - Hematopoietic development and homeostasis are based on hematopoietic stem cells
      (HSCs), a pool of ancestor cells characterized by the unique combination of self
      renewal and multilineage potential. These two opposing forces are finely
      orchestrated by several regulatory mechanisms, comprising both extrinsic and
      intrinsic factors. Over the past decades, several studies have contributed to
      dissect the key role of niche factors, signaling transduction pathways, and
      transcription factors in HSC development and maintenance. Accumulating evidence,
      however, suggests that a higher level of intrinsic regulation exists; epigenetic
      marks, by controlling chromatin accessibility, directly shape HSC developmental
      cascades, including their emergence during embryonic development, maintenance of
      self-renewal, lineage commitment, and aging. In addition, aberrant epigenetic
      marks have been found in several hematological malignancies, consistent with
      clinical findings that mutations targeting epigenetic regulators promote
      leukemogenesis. In this review, we will focus on both normal and malignant
      hematopoiesis, covering recent findings that illuminate the epigenetic life of
      HSCs. 

PMID- 24439803
TI  - Intestinal stem cells and their defining niche.
AB  - The intestinal epithelium is a classic example of a rapidly self-renewing tissue
      fueled by dedicated resident stem cells. These stem cells reside at the crypt
      base, generating committed progeny that mature into the various functional
      epithelial lineages while following a rapid migratory path toward the villi. Two
      models of intestinal stem cell location were proposed half a century ago and data
      have been presented in support of both models, dividing the scientific community.
      Molecular markers have been identified and validated using new techniques such as
      in vivo lineage tracing and ex vivo organoid culture. The intestinal stem cell
      niche comprises both epithelial cells, in particular the Paneth cell, and the
      stromal compartment, where cell-associated ligands and soluble factors regulate
      stem cell behavior. This review highlights the recent advances in identifying and
      characterizing the intestinal stem cells and their defining niche. 

PMID- 24439805
TI  - The mammary stem cell hierarchy.
AB  - The mammary epithelium undergoes enormous morphogenetic changes during the
      lifespan of a mammal. The recent elucidation of an epithelial differentiation
      hierarchy in the mouse mammary gland through classical transplantation and
      clonogenic assays has pointed to the existence of multipotent mammary stem cells
      (MaSCs) and at least two distinct luminal progenitor types. Moreover, an
      analogous functional hierarchy has been defined in human breast tissue. The
      existence of slow cycling stem cells, both long- and short-term repopulating
      cells, and a unique fetal MaSC population, imply a complex stem cell compartment
      within the mammary gland. The recent discovery of unipotent stem-like cells from
      lineage tracing studies has added a further layer of complexity to the emerging
      differentiation hierarchy. Although the precise relationships between stem and
      progenitor cells have yet to be resolved, the epithelial hierarchy has provided
      an important framework for elucidating the roles of molecular regulators of
      mammary gland ontogeny and understanding potential cells of origin in breast
      cancer. 

PMID- 24439806
TI  - Satellite cells: the architects of skeletal muscle.
AB  - The outstanding regenerative capacity of skeletal muscle is attributed to the
      resident muscle stem cell termed satellite cell. Satellite cells are essential
      for skeletal muscle regeneration as they ultimately provide the myogenic
      precursors that rebuild damaged muscle tissue. Satellite cells characteristically
      are a heterogeneous population of stem cells and committed progenitor cells.
      Delineation of cellular hierarchy and understanding how lineage fate choices are
      determined within the satellite cell population will be invaluable for the
      advancement of muscle regenerative therapies. 

PMID- 24439804
TI  - Epithelial stem cells in adult skin.
AB  - The skin is the first line of defense against dehydration and external
      environmental aggressions. It constantly renews itself throughout adult life
      mainly due to the activity of tissue-specific stem cells. In this review, we
      discuss fundamental characteristics of different stem cell populations within the
      skin and how they are able to contribute to normal skin homeostasis. We also
      examine the most recent results regarding the cell-intrinsic and -extrinsic
      components of the stem cell niche within the adult skin epithelium. Finally, we
      address the recent efforts to understand how abnormal regulation of stem cell
      activity contributes to the initiation and progression of skin-associated
      cancers. 

PMID- 24439807
TI  - Neural stem cell of the hippocampus: development, physiology regulation, and
      dysfunction in disease.
AB  - The formation of the hippocampus is generated during embryonic development, but
      most neurons within the structure are produced after birth. The hippocampus is a
      primary region of neurogenesis within the adult mammalian brain. Adult-born
      neurons have to integrate into the established neural circuitry throughout life.
      Although the function of neurogenesis in the adult hippocampus, particularly in
      humans, remains unclear, experimental data suggest that adult-born neurons are
      involved in some forms of memory, as well as in diseases. Adult hippocampal
      neurogenesis is dynamic, responding to physiological and pathological stimuli
      that may promote brain function or contribute to diseases such as epilepsy. Here,
      we review some of the mechanisms and signaling pathways involved in the
      development of the hippocampus, as well as in adult neurogenesis. We discuss some
      recent findings suggesting heterogeneity within the hippocampal stem cell pool
      and the regulation of activation of quiescent stem cells. Finally, we discuss
      some of the issues relating neurogenesis to pathophysiology and aging. 

PMID- 24439809
TI  - Spermatogonial stem cell functions in physiological and pathological conditions.
AB  - Sperm have a vital role in the continuity of a species by contributing genetic
      information to the next generation. Production of these specialized gametes in
      numbers sufficient to confer normal fertility occurs via cycling of the
      spermatogenic lineage, a process referred to as spermatogenesis. Continuity
      relies on the activities of a self-renewing reservoir of spermatogonial stem
      cells (SSCs) from which progenitors will arise that transiently amplify in number
      before committing to a pathway of terminal differentiation. A primary population
      of SSCs is established during neonatal development from a pool of quiescent
      gonocyte precursors that forms in embryogenesis. Disruption of this process has
      dire consequences on maintenance of a cycling spermatogenic lineage in adulthood.
      At present, the molecular mechanisms underlying initial formation of the SSC pool
      are largely undefined. However, several transcription factors and
      posttranscriptional regulators have been identified as important regulators of
      SSC self-renewal from studies with mutant mouse models and experimental
      manipulation within primary cultures of mouse SSCs. Importantly, loss of function
      of these self-renewal factors may be underlying causes of infertility.
      Furthermore, disruption in the establishment of the SSC state within gonocytes or
      misregulation of self-renewal may manifest as testicular germ cell tumors in
      postnatal life. 

PMID- 24439808
TI  - Lung stem and progenitor cells in tissue homeostasis and disease.
AB  - The mammalian lung is a complex organ containing numerous putative
      stem/progenitor cell populations that contribute to region-specific tissue
      homeostasis and repair. In this review, we discuss recent advances in identifying
      and studying these cell populations in the context of lung homeostasis and
      disease. Genetically engineered mice now allow for lineage tracing of several
      lung stem and progenitor cell populations in vivo during different types of lung
      injury repair. Using specific sets of cell surface markers, these cells can also
      be isolated from murine and human lung and tested in 3D culture systems and in
      vivo transplant assays. The pathology of devastating lung diseases, including
      lung cancers, is likely in part due to dysregulation and dysfunction of lung stem
      cells. More precise characterization of stem cells with identification of new,
      unique markers; improvement in isolation and transplant techniques; and further
      development of functional assays will ultimately lead to new therapies for a host
      of human lung diseases. In particular, lung cancer biology may be greatly
      informed by findings in normal lung stem cell biology as evidence suggests that
      lung cancer is a disease that begins in, and may be driven by, neoplastic lung
      stem cells. 

PMID- 24439811
TI  - Nephron progenitor cells: shifting the balance of self-renewal and
      differentiation.
AB  - Within the developing mammalian kidney, several populations of progenitors form
      the discrete cellular components of the final organ. Fate mapping experiments
      revealed the cap mesenchyme (CM) to be the progenitor population for all nephron
      epithelial cells, whereas the neighboring stromal mesenchyme gives rise to
      mesangial, pericytic, renin-producing and interstitial cells. The collecting
      ducts are derived from a population of progenitors at the ureteric bud (UB) tip
      and a proportion of the endothelium is also derived from a dedicated mesenchymal
      progenitor. The stroma, CM, and UB interact to create spatially defined niches at
      the periphery of the developing organ. While the UB tip population persist, the
      CM represents a transient progenitor population that is exhausted to set the
      final organ size. The timing of CM exhaustion, and hence the final organ
      structure, is sensitive to disruptions such as premature birth. Here we will
      discuss our current understanding of the molecular processes allowing these
      populations to balance cell survival, self-renewal, support of branching, and
      maintain capacity to commit to differentiation. 

PMID- 24439810
TI  - The origin, biology, and therapeutic potential of facultative adult hepatic
      progenitor cells.
AB  - The liver plays an essential role in glucose and lipid metabolism, synthesis of
      plasma proteins, and detoxification of xenobiotics and other toxins. Chronic
      disease of this important organ is one of the leading causes of death in the
      United States. Following loss of tissue, liver mass can be restored by two
      mechanisms. Under normal conditions, or after massive loss of parenchyma by
      surgical resection, liver mass is maintained by division of hepatocytes. After
      chronic injury, or when proliferation of hepatocytes is impaired, facultative
      adult hepatic progenitor cells (HPCs) proliferate and differentiate into
      hepatocytes and cholangiocytes (biliary epithelial cells). HPCs are attractive
      candidates for cell transplantation because of their potential contribution to
      liver regeneration. However, until recently, the lack of highly specific markers
      has hampered efforts to better understand the origin and physiology of HPCs.
      Recent advances in cell isolation methods and genetic lineage tracing have
      enabled investigators to explore multiple aspects of HPC biology. In this review,
      we describe the potential origins of HPCs, the markers used to detect them, the
      contribution of HPCs to recovery, and the signaling pathways that regulate their
      biology. We end with an examination of the therapeutic potential of HPCs and
      their derivatives. 

PMID- 24439812
TI  - Adult stem cell niches: cellular and molecular components.
AB  - As stem cells (SCs) in adult organs continue to be identified and characterized,
      it becomes clear that their survival, quiescence, and activation depend on
      specific signals in their microenvironment, or niche. Although adult SCs of
      diverse tissues differ by their developmental origin, cycling activity, and
      regenerative capacity, there appear to be conserved similarities regarding the
      cellular and molecular components of the SC niche. Interestingly, many organs
      house both slow-cycling and fast-cycling SC populations, which rely on the
      coexistence of quiescent and inductive niches for proper regulation. In this
      review we present a general definition of adult SC niches in the most studied
      mammalian systems. We further focus on dissecting their cellular organization and
      on highlighting recently identified key molecular regulators. Finally, we detail
      the potential involvement of the SC niche in tissue degeneration, with a
      particular emphasis on aging and cancer. 

PMID- 24439813
TI  - Cancer stem cells, pluripotency, and cellular heterogeneity: a WNTer perspective.
AB  - Cancer stem cells (CSCs) are thought to represent the "beating heart" of
      malignant growth as they continuously fuel tumors through their ability to self
      renew and differentiate. Moreover, they are also believed to underlie malignant
      behavior, local invasion, and metastasis in distal organ sites upon reversible
      epithelial-to-mesenchymal transitions (EMTs). Nevertheless, the CSC concept has
      been the object of controversy, mainly due to the absence of robust operational
      definitions and to the lack of consistency in the use of the often incorrect
      nomenclature employed to refer to these cells. Notwithstanding the controversies,
      it is now generally accepted that primary cancers are organized in hierarchical
      fashion with neoplastic stem-like cells able to give rise to new CSCs and to more
      committed malignant cells. Notably, these hierarchical structures are not
      unidirectional, but are rather characterized by a more dynamic equilibrium where
      stem-like and more committed cancer cells transit from one meta-state to the
      other partly because of cues from the microenvironment (niche), but also because
      of intrinsic and yet incompletely understood characteristics in the
      activation/silencing of specific signal transduction pathways. Here, we will
      focus on the Wnt/beta-catenin signaling pathway as one of the major regulator of
      stemness in homeostasis and cancer, and on germ cell tumors as the type of
      malignancy that most closely mimics normal embryonic development and as such
      serve as a unique model to study the role of stem cells in neoplasia. 

PMID- 24439815
TI  - Preface. Stem cells in development and disease.

PMID- 24439818
TI  - Inadequate vitamin B-12 intake may be a problem not just for a small number of
      Adventist vegans.

PMID- 24439819
TI  - Authors' response.

PMID- 24439820
TI  - Position and practice paper update for 2014.

PMID- 24439814
TI  - Cellular mechanisms of somatic stem cell aging.
AB  - Tissue homeostasis and regenerative capacity rely on rare populations of somatic
      stem cells endowed with the potential to self-renew and differentiate. During
      aging, many tissues show a decline in regenerative potential coupled with a loss
      of stem cell function. Cells including somatic stem cells have evolved a series
      of checks and balances to sense and repair cellular damage to maximize tissue
      function. However, during aging the mechanisms that protect normal cell function
      begin to fail. In this review, we will discuss how common cellular mechanisms
      that maintain tissue fidelity and organismal lifespan impact somatic stem cell
      function. We will highlight context-dependent changes and commonalities that
      define aging, by focusing on three age-sensitive stem cell compartments: blood,
      neural, and muscle. Understanding the interaction between extrinsic regulators
      and intrinsic effectors that operate within different stem cell compartments is
      likely to have important implications for identifying strategies to improve
      health span and treat age-related degenerative diseases. 

PMID- 24439821
TI  - Position of the Academy of Nutrition and Dietetics: nutritional genomics.
AB  - It is the position of the Academy of Nutrition and Dietetics that nutritional
      genomics provides insight into how diet and genotype interactions affect
      phenotype. The practical application of nutritional genomics for complex chronic
      disease is an emerging science and the use of nutrigenetic testing to provide
      dietary advice is not ready for routine dietetics practice. Registered dietitian
      nutritionists need basic competency in genetics as a foundation for understanding
      nutritional genomics; proficiency requires advanced knowledge and skills. Unlike
      single-gene defects in which a mutation in a single gene results in a specific
      disorder, most chronic diseases, such as cardiovascular disease, diabetes, and
      cancer are multigenetic and multifactorial and therefore genetic mutations are
      only partially predictive of disease risk. Family history, biochemical
      parameters, and the presence of risk factors in individuals are relevant tools
      for personalizing dietary interventions. Direct-to-consumer genetic testing is
      not closely regulated in the United States and may not be accompanied by access
      to health care practitioners. Applying nutritional genomics in clinical practice
      through the use of genetic testing requires that registered dietitian
      nutritionists understand, interpret, and communicate complex test results in
      which the actual risk of developing a disease may not be known. The practical
      application of nutritional genomics in dietetics practice will require an
      evidence-based approach to validate that personalized recommendations result in
      health benefits to individuals and do not cause harm.

PMID- 24439822
TI  - 2013 Lenna Frances Cooper Memorial Lecture: Bringing cooking back: food and
      culinary expertise as a key to dietitians' future success.

PMID- 24439823
TI  - Was there a recent update to the FDA food code?

PMID- 24439826
TI  - Bioactive compound from Pseudomonas synxantha inhibits the growth of
      Mycobacteria.
AB  - Tuberculosis is a dreaded disease and the current situation demands new anti
      tubercular agent(s) for the management of public health. Towards this direction,
      we obtained a contaminant organism on a Mycobacterium smegmatis lawn having
      growth inhibitory activity against the later. In the current study, efforts were
      targeted to identify this organism and characterize the bioactive compound from
      this isolate that inhibited the growth of Mycobacteria. The result revealed that
      the organism is a strain of Pseudomonas synxantha. Biophysical analyses including
      (1)H and (13)C NMR, ESI-mass spectroscopy, FTIR showed that the bioactive
      compound is a long chain aliphatic hydrocarbon with a terminal alyl bond and
      intermediate electronegative atom. The compound exhibited strong growth
      inhibitory activities against M. smegmatis and Mycobacterium tuberculosis strains
      H37Ra, H37Rv and BCG. Further experiments showed that both P. synxantha and its
      secretory metabolites are capable of inducing hemolysis of human blood. Thus the
      results of this study clearly indicate that the bioactive compound produced by P.
      Synxantha has biosurfactant activities as well as anti-myco-bacterial properties.

PMID- 24439827
TI  - Os2 MAP kinase-mediated osmostress tolerance in Penicillium digitatum is
      associated with its positive regulation on glycerol synthesis and negative
      regulation on ergosterol synthesis.
AB  - High osmolarity glycerol (HOG) pathway is ubiquitously distributed among
      eukaryotic organisms and plays an important role in adaptation to changes in the
      environment. In this study, the Hog1 ortholog in Penicillium digitatum,
      designated Pdos2, was identified and characterized using a gene knock-out
      strategy. The DeltaPdos2 mutant showed a considerably increased sensitivity to
      salt stress and cell wall-disturbing agents and a slightly increased resistance
      to fungicides iprodione and fludioxonil, indicating that Pdos2 is involved in
      response to hyperosmotic stress, regulation of cell wall integrity and
      sensitivity to fungicides iprodione and fludioxonil. Surprisingly, the mutant was
      not affected in response to oxidative stress caused by H2O2. The average lesion
      size in citrus fruits caused by DeltaPdos2 mutant was smaller (approximately
      25.0% reduction) than that caused by the wild-type strain of P. digitatum at 4
      days post inoculation, which suggests that Pdos2 is needed for full virulence of
      P. digitatum. Interestingly, in the presence of 0.7 M NaCl, the glycerol content
      was remarkably increased and the ergosterol was decreased in mycelia of the wide
      type P. digitatum, whereas the glycerol content was only slightly increased and
      the ergosterol content remained stable in the DeltaPdos2 mutant, suggesting that
      Pdos2-mediated osmotic adaption is associated with its positive regulation on
      glycerol synthesis and negative regulation on ergosterol synthesis.

PMID- 24439828
TI  - The Staphylococcus aureus proteome.
AB  - Staphylococcus aureus is a Gram-positive commensal bacterium that is regarded as
      a major threat for modern health care systems. This relates both to the ability
      of S. aureus to overcome antibiotic therapy by developing high-level resistance
      against multiple antibiotics and this bacterium's extensive arsenal of virulence
      factors. Understanding the mechanisms of resistance and functional studies on
      stress and starvation responses are the main goals of proteomics in
      staphylococcal research. This review high-lights recent advances in gel-based and
      gel-free proteomics analyses of S. aureus and pinpoints the importance of
      location-specific proteomics studies targeting the cytosol, the membrane, the
      cell surface and the extracellular milieu in combination with integrated global
      proteome studies. Emerging hot topics in staphylococcal proteomics are discussed
      with special focus on in vivo proteomics, membrane vesicles, biofilm formation
      and the acquisition of absolute proteome data for systems biological modeling
      approaches. 

PMID- 24439829
TI  - Psychosocial interventions in bipolar disorder: what, for whom, and when.
AB  - BACKGROUND: Bipolar disorder (BD) is a chronic condition with a high relapse
      rate, morbidity and psychosocial impairment that often persist despite
      pharmacotherapy, highlighting the need for adjunctive psychosocial treatments. It
      is still unclear which populations are most likely to benefit from which approach
      and the best timing to implement them. METHODS: A review was conducted with the
      aim to determine what the efficacious psychological treatments are, for whom and
      when. Randomized-controlled trials and key studies in adults with BD published
      until June 2013 were included RESULTS: The adjunctive psychological treatments
      most commonly tested in BD were cognitive-behavioral therapy, psychoeducation,
      interpersonal and social rhythm therapy, and family intervention. The efficacy of
      specific adjunctive psychosocial interventions has been proven not only in short-
      but also long-term follow-up for some treatments. Outcomes vary between studies,
      with most trials focused on clinical variables like recurrence prevention or
      symptom reduction and less attention, although gradually expanding, paid to other
      aspects such as psychosocial functioning. The samples were usually in remission
      or with mild symptoms when recruited but there were a few studies with acute
      patients, which resulted in discrepant findings. The efficacy of psychological
      interventions seems to differ depending on the characteristics of the subjects
      and the course of the illness. Different approaches, such as functional
      remediation and mindfulness-based cognitive therapy, have begun to be tested in
      BD. LIMITATIONS: Heterogeneity of comparison groups. CONCLUSIONS: Adjunctive
      psychological treatments can improve BD outcomes. Although several moderators and
      mediators have been identified, more research is needed to design shorter but
      effective interventions tailored to the characteristics of the target population.
      Ideally, the treatment should be introduced as soon as possible, although it does
      not mean that more complex patients would not benefit from psychotherapy.

PMID- 24439831
TI  - Phenomenology of manic episodes according to the presence or absence of
      depressive features as defined in DSM-5: Results from the IMPACT self-reported
      online survey.
AB  - BACKGROUND: The aim of this study was to describe the phenomenology of mania and
      depression in bipolar patients experiencing a manic episode with mixed features
      as defined in the new Diagnostic and Statistical Manual of Mental Disorders (DSM
      5). METHODS: In this multicenter, international on-line survey (the IMPACT
      study), 700 participants completed a 54-item questionnaire on demographics,
      diagnosis, symptomatology, communication of the disease, impact on life, and
      treatment received. Patients with a manic episode with or without DSM-5 criteria
      for mixed features were compared using descriptive and inferential statistics.
      RESULTS: Patients with more than 3 depressive symptoms were more likely to have
      had a delay in diagnosis, more likely to have experienced shorter symptom-free
      periods, and were characterized by a marked lower prevalence of typical manic
      manifestations. All questionnaire items exploring depressive symptomatology,
      including the DSM-5 criteria defining a manic episode as "with mixed features",
      were significantly overrepresented in the group of patients with depressive
      symptoms. Anxiety associated with irritability/agitation was also more frequent
      among patients with mixed features. LIMITATIONS: Retrospective cross-sectional
      design, sensitive to recall bias. Two of the 6 DSM-5 required criteria for the
      specifier "with mixed features" were not explored: suicidality and psychomotor
      retardation. CONCLUSIONS: Bipolar disorder patients with at least 3 depressive
      symptoms during a manic episode self-reported typical symptomatology. Anxiety
      with irritability/agitation differentiated patients with depressive symptoms
      during mania from those with "pure" manic episodes. The results support the use
      of DSM-5 mixed features specifier and its value in research and clinical
      practice.

PMID- 24439836
TI  - Adaptive PCA based fault diagnosis scheme in imperial smelting process.
AB  - In this paper, an adaptive fault detection scheme based on a recursive principal
      component analysis (PCA) is proposed to deal with the problem of false alarm due
      to normal process changes in real process. Our further study is also dedicated to
      develop a fault isolation approach based on Generalized Likelihood Ratio (GLR)
      test and Singular Value Decomposition (SVD) which is one of general techniques of
      PCA, on which the off-set and scaling fault can be easily isolated with explicit
      off-set fault direction and scaling fault classification. The identification of
      off-set and scaling fault is also applied. The complete scheme of PCA-based fault
      diagnosis procedure is proposed. The proposed scheme is first applied to Imperial
      Smelting Process, and the results show that the proposed strategies can be able
      to mitigate false alarms and isolate faults efficiently. 

PMID- 24439830
TI  - Measuring treatment response in psychotic depression: the Psychotic Depression
      Assessment Scale (PDAS) takes both depressive and psychotic symptoms into
      account.
AB  - BACKGROUND: There is no established psychometric instrument dedicated to the
      measurement of severity in psychotic depression (PD). The aim of this study was
      to investigate whether a new composite rating scale, the Psychotic Depression
      Assessment Scale (PDAS), covering both the psychotic and the depressive domains
      of PD, could detect differences in effect between two psychopharmacological
      treatment regimens. METHODS: We reanalyzed the data from the Study of
      Pharmacotherapy of Psychotic Depression (STOP-PD), which compared the effect of
      Olanzapine+Sertraline (n=129) versus Olanzapine+Placebo (n=130). The response to
      the two regimens was compared using both a mixed effects model and effect size
      statistics on the total scores of three rating scales: the 17-item Hamilton
      Depression Rating Scale (HAM-D17), its 6-item melancholia subscale (HAM-D6), and
      the 11-item PDAS consisting of the HAM-D6 plus five items from the Brief
      Psychiatric Rating Scale covering psychotic symptoms. RESULTS: According to both
      statistical approaches, the PDAS, the HAM-D17 and the HAM-D6 were all able to
      detect significant differences in treatment effect between Olanzapine+Sertraline
      and Olanzapine+Placebo (Olanzapine+Sertraline being superior). Notably, 45% of
      the trial participants were at least "probable psychotic" at their last
      assessment in the trial. LIMITATIONS: The STOP-PD was not designed specifically
      to answer the research questions of the present study. CONCLUSIONS: The Psychotic
      Depression Assessment Scale (PDAS) is a sensitive measure of treatment response
      in PD. The fact that 45% of the patients still experienced psychotic symptoms at
      their last trial assessment emphasizes the need to include items pertaining to
      psychotic symptoms in rating scales for PD.

PMID- 24439837
TI  - Effect of initial solution pH on photo-induced reductive decomposition of
      perfluorooctanoic acid.
AB  - The effects of initial solution pH on the decomposition of perfluorooctanoic acid
      (PFOA) with hydrated electrons as reductant were investigated. The reductive
      decomposition of PFOA depends strongly on the solution pH. In the pH range of 5.0
      10.0, the decomposition and defluorination rates of PFOA increased with the
      increase of the initial solution pH. The rate constant was 0.0295 min(-1) at pH
      10.0, which was more than 49.0 times higher than that at pH 5.0. Higher pH also
      inhibits the generation of toxic intermediates during the PFOA decomposition. For
      example, the short-chain PFCAs reached a lower maximum concentration in shorter
      reaction time as pH increasing. The peak areas of accumulated fluorinated and
      iodinated hydrocarbons detected by GC/MS under acidic conditions were nearly 10
      100 times more than those under alkaline conditions. In short, alkaline
      conditions were more favorable for photo-induced reduction of PFOA as high pH
      promoted the decomposition of PFOA and inhibited the accumulation of intermediate
      products. The concentration of hydrated electron, detected by laser flash
      photolysis, increased with the increase of the initial pH. This was the main
      reason why the decomposition of PFOA in the UV-KI system depended strongly on the
      initial pH.

PMID- 24439838
TI  - Oxidation of Orange G by persulfate activated by Fe(II), Fe(III) and zero valent
      iron (ZVI).
AB  - Persulfate (PS) was employed in the oxidation of Orange G (OG), an azo dye
      commonly found in textile wastewaters. Activation of PS was conducted with iron
      to generate sulfate free radicals (SO4(-)) with high redox potential capable to
      oxidize most of the organics in water. Identification of oxidation intermediates
      was carried out by analyzing at different times organic by-products generated
      from treatment of a concentrate dye solution (11.6 mM) with 153 mM of PS and 20
      mM of Fe(II) at 20  degrees C. Intermediate reaction products (mainly phenol (PH)
      and benzoquinone (BQ), and in less extent aniline, phenolic compounds and
      naphthalene type compounds with quinone groups) were identified by GC/MS and
      HPLC, and an oxidation pathway was proposed for the oxidation of OG with iron
      activated PS. The effect of iron valence (0, II and III) in the oxidation of an
      aqueous solution of OG (containing 0.1 mM) was studied in a 0.5 L batch reactor
      at 20  degrees C. Initial activator and PS concentrations employed were both 1
      mM. Complete pollutant removal was achieved within the first 30 min when iron II
      or III were employed as activators. Quinone intermediates generated during
      pollutant oxidation may act as electron shuttles, allowing the reduction of
      Fe(III) into Fe(II) in the redox cycling of iron. Therefore, activation of PS by
      Fe(III) allowed complete OG removal. When zero valent iron (ZVI) was employed
      (particle diameter size 0.74 mm) the limiting step in SO4(-) generation was the
      surface reaction between ZVI and the oxidant yielding a lower oxidation rate of
      the dye. An increase in the oxidant dosage (0.2 mM OG, 2 mM Fe(III) and 6 mM PS)
      allowed complete pollutant and ecotoxicity removal, as well as mineralization
      close to 75%.

PMID- 24439839
TI  - Bronchial carcinoid tumor presenting with recurrent pneumothorax.

PMID- 24439840
TI  - The management of anthelmintic resistance in grazing ruminants in Australasia-
      strategies and experiences.
AB  - In many countries the presence of anthelmintic resistance in nematodes of small
      ruminants, and in some cases also in those infecting cattle and horses, has
      become the status quo rather than the exception. It is clear that consideration
      of anthelmintic resistance, and its management, should be an integral component
      of anthelmintic use regardless of country or host species. Many years of research
      into understanding the development and management of anthelmintic resistance in
      nematodes of small ruminants has resulted in an array of strategies for
      minimising selection for resistance and for dealing with it once it has
      developed. Importantly, many of these strategies are now supported by empirical
      science and some have been assessed and evaluated on commercial farms. In sheep
      the cost of resistance has been measured at about 10% of the value of the lamb at
      sale which means that losses due to undetected resistance far outweigh the cost
      of testing anthelmintic efficacy. Despite this many farmers still do not test for
      anthelmintic resistance on their farm. Many resistance management strategies have
      been developed and some of these have been tailored for specific environments
      and/or nematode species. However, in general, most strategies can be categorised
      as either; identify and mitigate high risk management practices, maintain an
      anthelmintic-susceptible population in refugia, choose the optimal anthelmintic
      (combinations and formulations), or prevent the introduction of resistant
      nematodes. Experiences with sheep farmers in both New Zealand and Australia
      indicate that acceptance and implementation of resistance management practices is
      relatively easy as long as the need to do so is clear and the recommended
      practices meet the farmer's criteria for practicality. A major difference between
      Australasia and many other countries is the availability and widespread
      acceptance of combination anthelmintics as a resistance management tool. The
      current situation in cattle and horses in many countries indicates a failure to
      learn the lessons from resistance development in small ruminants. The cattle and
      equine industries have, until quite recently, remained generally oblivious to the
      issue of anthelmintic resistance and the need to take pre-emptive action. In
      Australasia, as in other countries, a perception was held that resistance in
      cattle parasites would develop very slowly, if it developed at all. Such
      preconceptions are clearly incorrect and the challenge ahead for the cattle and
      equine industries will be to maximise the advantages for resistance management
      from the extensive body of research and experience gained in small ruminants. 

PMID- 24439841
TI  - Breastfeeding and the maternal risk of type 2 diabetes: a systematic review and
      dose-response meta-analysis of cohort studies.
AB  - BACKGROUND AND AIMS: Breastfeeding has been associated with reduced risk of
      maternal type 2 diabetes in some cohort studies, but the evidence from published
      studies have differed with regard to the strength of the association. To clarify
      this association we conducted a systematic review and dose-response meta-analysis
      of breastfeeding and maternal risk of type 2 diabetes. METHODS AND RESULTS: We
      conducted a systematic review and dose-response meta-analysis of prospective
      studies of breastfeeding and maternal risk of type 2 diabetes. We searched the
      PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative
      risks were estimated using a random effects model. Six cohort studies including
      10,842 cases among 273,961 participants were included in the meta-analysis. The
      summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95%
      CI: 0.57-0.82, I(2) = 75%, p heterogeneity = 0.001, n = 6). The summary RR for a
      three month increase in the duration of breastfeeding per child was 0.89 (95% CI:
      0.77-1.04, I(2) = 93%, p heterogeneity < 0.0001, n = 3) and the summary RR for a
      one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86
      0.96, I(2) = 81%, p heterogeneity = 0.001, n = 4). There was little difference in
      the summary estimates whether or not BMI had been adjusted for. The inverse
      associations appeared to be nonlinear, p nonlinearity < 0.0001 for both analyses,
      and in both analyses the reduction in risk was steeper when increasing
      breastfeeding from low levels. CONCLUSION: This meta-analysis suggests that there
      is a statistically significant inverse association between breastfeeding and
      maternal risk of type 2 diabetes.

PMID- 24439843
TI  - Robust fault detection of turbofan engines subject to adaptive controllers via a
      Total Measurable Fault Information Residual (ToMFIR) technique.
AB  - This paper provides a new design of robust fault detection for turbofan engines
      with adaptive controllers. The critical issue is that the adaptive controllers
      can depress the faulty effects such that the actual system outputs remain the pre
      specified values, making it difficult to detect faults/failures. To solve this
      problem, a Total Measurable Fault Information Residual (ToMFIR) technique with
      the aid of system transformation is adopted to detect faults in turbofan engines
      with adaptive controllers. This design is a ToMFIR-redundancy-based robust fault
      detection. The ToMFIR is first introduced and existing results are also
      summarized. The Detailed design process of the ToMFIRs is presented and a
      turbofan engine model is simulated to verify the effectiveness of the proposed
      ToMFIR-based fault-detection strategy. 

PMID- 24439842
TI  - Metabolic syndrome and long-term cardiovascular outcomes in NSTEMI with unstable
      angina.
AB  - BACKGROUND AND AIM: Metabolic syndrome (MS) is associated with cardiovascular
      mortality and morbidity in patients with acute coronary syndrome. The purpose of
      this study was to evaluate the impact of MS on long-term clinical outcomes in
      patients with pure non-ST segment myocardial infarction (NSTEMI) or unstable
      angina pectoris (USAP). METHODS AND RESULTS: We prospectively enrolled 310
      consecutive NSTEMI/USAP patients (74 females; mean age, 59.3 +/- 11.9 years). The
      study population was divided into two groups: MS(+) and MS(-). The clinical
      outcomes of the patients were followed for up to 3 years. Increased 3-year
      cardiovascular mortality and reinfarction were observed in the MS(+) group, as
      compared to the MS(-) group (15 vs. 3.4%, p = 0.001, and 22.2 vs. 8.3%, p =
      0.001, respectively). Hospitalization rates for heart failure and stroke were not
      significantly different between the two groups on follow-up. By a Cox
      multivariate analysis, a significant association was noted between MS and the
      adjusted risk of 3-year cardiovascular mortality (odds ratio 3.4, 95% confidence
      interval, 1.24-9.1, p = 0.02). CONCLUSION: These results suggest that MS is
      associated with an increased risk of 3-year cardiovascular mortality and
      reinfarction in patients with NSTEMI/USAP.

PMID- 24439844
TI  - Does adherence to National Comprehensive Cancer Network guidelines improve pain
      related outcomes? An evaluation of inpatient cancer pain management at an
      academic medical center.
AB  - CONTEXT: Evidence-based guidelines are in place for the management of cancer
      related pain, yet adherence remains problematic throughout health systems because
      of efficacy and safety concerns. OBJECTIVES: To evaluate adherence to the
      National Comprehensive Cancer Network (NCCN) guidelines on pain management among
      cancer inpatients and assess whether adherence is associated with pain control.
      METHODS: A retrospective chart review of patients admitted to the
      hematology/oncology service at an academic medical center between April 1, 2011
      and September 30, 2011 was conducted, and patients were allocated into groups
      based on adherence to NCCN guidelines. Pain control and safety outcomes were
      compared between adherence groups for the first 24 hours of hospital admission.
      Multivariate analyses were performed to identify predictors of regimens
      nonadherent to guidelines and predictors of inadequate achievement of analgesia.
      RESULTS: Among a random sample of 193 inpatients, 109 met the inclusion criteria
      of which 70 were guideline adherent and 39 nonadherent. A total of 63% of the
      patients initiated on NCCN adherent guidelines obtained analgesia at 24 hours
      compared with 41% in the nonadherent group (P=0.028). Average pain scores across
      the 24-hour period were lower in the adherent compared with the nonadherent group
      (3.5 vs. 4.4, respectively, P<0.001). Naloxone use, respiratory depression, and
      hypoxia did not significantly vary between adherence groups. Chronic home opioid
      exposure was significantly associated with nonadherent therapy (vs. adherent;
      odds ratio=3.04, confidence interval=1.28-7.18, P=0.01) and achievement of
      analgesia at 24 hours (vs. not; odds ratio=0.30, confidence interval=0.12-0.73,
      P<0.01). CONCLUSION: Adherence to NCCN guidelines remains insufficient, with
      nonadherence being associated with inadequate analgesia. Opioid-tolerant patients
      remain at higher risk for guideline nonadherence and inadequate analgesia.
      Quality improvement initiatives should target opioid-tolerant patients.

PMID- 24439846
TI  - Progressive development and enhancement of palliative care services in Japan:
      nationwide surveys of designated cancer care hospitals for three consecutive
      years.
AB  - CONTEXT: Policymaking plays an important role in national palliative care
      services. The Japanese Cancer Control Act was implemented in 2006. OBJECTIVES: To
      evaluate changes in the structure and processes of palliative care services after
      implementation of the Cancer Control Act. METHODS: We conducted annual nationwide
      surveys in designated cancer care hospitals (DCCHs, n = 349) between 2008 and
      2010. The 65-item questionnaire was divided into seven domains: institutional
      framework, information to patient and family, practice of palliative care,
      activities of the palliative care teams (PCTs), members of PCTs, regional medical
      cooperation, and education. Increasing trends were tested using generalized
      estimating equation models. RESULTS: The response rates were >= 99%. All domains
      showed an increasing trend (P < 0.001). There were significant increases in full
      time PCT physicians (27.4%-45.7%, P(trend) < 0.001), full-time PCT nurses (38.9%
      88.0%, P(trend) < 0.001), and the median number of annual referrals to PCTs (60
      80 patients, P < 0.001). Essential drugs were available in most DCCHs from
      baseline. Although outpatient clinics increased significantly (27.0%-58.9%,
      P(trend) < 0.001), community outreach programs did not (9.0%-12.6%, P = 0.05).
      Basic education was actively introduced for in-hospital physicians and nurses
      (78.2% and 91.4% in 2010), but often unavailable for regional health care
      providers (basic education for regional physicians and nurses: 63.9% and 71.1% in
      2010). CONCLUSION: The Cancer Control Act promoted the development and
      enhancement of palliative care services in DCCHs. Regional medical cooperation
      and education are the future challenges of palliative care in Japan.

PMID- 24439845
TI  - Fatigue in family caregivers of adult intensive care unit survivors.
AB  - CONTEXT: Family caregivers are a vital resource in the recovery of intensive care
      unit (ICU) survivors. Of concern, the stress associated with this role can
      negatively affect caregiver health. Fatigue, an important health indicator, has
      been identified as a predictor of various illnesses, greater use of health
      services, and early mortality. Examining the impact of fatigue on caregivers'
      physical health can assist in identifying critical time points and potential
      targets for intervention. OBJECTIVES: To describe self-reported fatigue in
      caregivers of ICU survivors from patients' ICU admission to <= 2 weeks, two- and
      four-months post-ICU discharge. METHODS: Patient-caregiver pairs were enrolled
      from a medical ICU. Caregiver fatigue was measured using the Short-Form 36 Health
      Survey Vitality subscale (SF-36 Vitality). Caregiver psychobehavioral stress
      responses included depressive symptoms, burden, health risk behaviors, and sleep
      quality. Patient data included self-reported physical symptoms and disposition
      (home vs. institution). RESULTS: Forty-seven patient-caregiver pairs were
      initially enrolled. Clinically significant fatigue (SF-36 Vitality <= 45) was
      reported by 43%-53% of caregivers across the time points, and these caregivers
      reported worse scores in measures of depressive symptoms, burden, health risk
      behaviors and sleep quality, and patients' symptom burden. In 26 caregivers with
      data for all time points (55% of the total sample), SF-36 Vitality scores showed
      trends of improvement when the patient returned home and greater impairment when
      institutionalization continued. CONCLUSION: In caregivers of ICU survivors,
      fatigue is common and potentially linked with poor psychobehavioral responses.
      Worsening fatigue was associated with greater symptom distress and long-term
      patient institutionalization.

PMID- 24439848
TI  - Molecular detection of equine trypanosomes in the Sudan.
AB  - Equine trypanosomosis (ET) is a protozoan disease affecting equines in many parts
      of the world. We examined 509 samples collected from geographically distinct
      regions in eastern, central and western Sudan to estimate the endemicity of ET
      using the generic ITS1-PCR diagnostic methods. Results revealed that horses and
      donkeys were infected by Trypanosoma brucei subgroup, Trypanosoma vivax,
      Trypanosoma simiae and Trypanosoma congolense. The prevalence of Trypanosoma spp.
      was higher in horses (12.7%, n=393) than in donkeys (3.4%, n=116). The highest
      prevalence was observed in South Darfur State (19.3%, n=202), followed by Kassala
      State (15.1%, n=86), Gadaref State (3.7%, n=82), and Khartoum State (2.6%, n=76).
      No trypanosomes were detected in the 63 samples collected from North Kurdofan
      State. We report for the first time the presence of T. simiae and T. congolense
      in horses in the Sudan. This study should alert veterinary services, authorized
      bodies to take action toward ET by undertaking countrywide epidemiological
      studies of the disease and adopting control strategies. 

PMID- 24439847
TI  - Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available
      inhibitors of dipeptidyl peptidase IV.
AB  - The successful launches of dipeptidyl peptidase IV (DPP IV) inhibitors as oral
      anti-diabetics warrant and spur the further quest for additional chemical
      entities in this promising class of therapeutics. Numerous pharmaceutical
      companies have pursued their proprietary candidates towards the clinic, resulting
      in a large body of published chemical structures associated with DPP IV. Herein,
      we report the discovery of a novel chemotype for DPP IV inhibition based on the C
      (1-aryl-cyclohexyl)-methylamine scaffold and its optimization to compounds which
      selectively inhibit DPP IV at low-nM potency and exhibit an excellent oral
      pharmacokinetic profile in the rat. 

PMID- 24439849
TI  - Impact of integrated gastrointestinal nematode management training for U.S. goat
      and sheep producers.
AB  - The objective of this study was to determine the impact of integrated parasite
      management (IPM) training, including FAMACHA((c)) eyelid color scoring, on the
      ability of U.S. sheep and goat producers to control gastrointestinal nematodes
      (GIN) on their farms. A survey was developed and provided to over 2000 producers
      trained from 2004 to 2008 in IPM with questions involving farm size (number of
      sheep/goats), location (U.S. state), impact of training on parasite control
      efforts and parasite problems on farm, and IPM practices used. Responses were
      divided into U.S. Census regions of the U.S. Descriptive statistics and logistic
      regression were used to describe results. Most of the 729 respondents were from
      the southern region of the U.S. (54.3%) and were small-scale producers (50 or
      less animals; 64.8%). Nearly all of the respondents (95.1%) agreed that IPM
      workshop attendance made a difference in their ability to control and monitor
      parasitism in their herd or flock and employed IPM practices to control GIN
      (96.3%). The most popular practices respondents used were rotational grazing
      (71.2%), genetic selection (choosing a parasite resistant breed and/or culling
      susceptible animals; 52.7%), grain supplementation on pasture to improve
      nutrition (44.0%), and increased height of plants being grazed (41.8%). Although
      reporting using a practice decreased (P<0.05) the likelihood of reporting fewer
      problems, for each 1-point increase in the number of practices which producers
      employed to control internal parasitism in their herd or flock, they were 16%
      more likely to report fewer GIN problems (P<0.05). Approximately 75% of
      respondents indicated an economic benefit of IPM on their farm (P<0.05), and
      those reporting savings of over $80 were more likely to report fewer problems
      (P<0.05) with parasites after the training while those reporting no economic
      benefit were less likely to report fewer problems with GIN (P<0.001). Overall,
      IPM training resulted in positive impacts for producers responding to the survey
      and should continue. 

PMID- 24439850
TI  - A search for hope and understanding: an analysis of threatened miscarriage
      internet forums.
AB  - OBJECTIVE: threatened miscarriage is a common complication of early pregnancy,
      which increases the risk of miscarriage or pregnancy complications such as
      premature birth. Currently there is limited evidence to recommend beneficial
      medical treatments or lifestyle changes, resulting in a 'watchful waiting'
      approach. The aim of this study was to describe women's experiences of threatened
      miscarriage through examining postings to Internet discussion forums. DESIGN: a
      Goggle alert for threatened miscarriage was created with emails containing
      hyperlinks sent to the first author and collected over a seven month period
      (April to November 2011). Data was analysed using thematic analysis. FINDINGS:
      one hundred and twenty one discussion threads were collected. The overarching
      theme that emerged was one of 'a search for hope and understanding'. Within this
      there were four sub themes that illustrated this search. 'A reason for hope:
      stories and real life experiences' illustrated how women sought hope for a viable
      pregnancy through others. 'Becoming the expert,' captures how women gave advice
      from their own experiences. 'A safe place to share' and 'connecting to empathic
      support' illustrates how women used this medium for long distance support. KEY
      CONCLUSION: internet discussion forums were used by women to seek hope and
      support they were not receiving from their health professionals. Women urged each
      other to remain hopeful despite a negative medical prognosis. There was an
      acceptance of a lay expertise within the forums that was valid enough to
      challenge medical expertise. IMPLICATIONS FOR PRACTICE: health practitioners may
      need education that helps them balance their delivery of medical information with
      hope in order to increase feelings of trust. With women seeing the Internet as a
      useful form of support, it may be relevant for practitioners to consider
      recommending relevant Internet sites and discuss this with women.

PMID- 24439851
TI  - [Experimental induction of Perthes disease in lambs].
AB  - OBJECTIVE: To establish a simple, reproducible and safe experimental model, for
      the development of ischemic vascular necrosis of the hip in the lamb. MATERIAL
      AND METHODS: We used 15 lambs (10 males and 5 females) aged four weeks, divided
      into a control group (7 animals) and an experimental group (8 animals) producing
      ischemia in the proximal femur. Standard radiography and MRI were performed. The
      animals were euthanised at the 4th, 8th and 12th weeks after surgery. The femoral
      heads were extracted and measured and a histological analysis was performed with
      hematoxylin-eosin staining. RESULTS: Decreased height and increased width of the
      femoral head was observed in the X-Rays, particularly after the 4th week. We did
      not observe any changes in the height of the lateral pillar or trochanteric
      distance. The experimental group showed macroscopical hypertrophy and progressive
      flattening of the head. At 4 weeks necrotic areas in articular cartilage were
      observed, bone marrow was dense and the growth cartilage height was lower. The
      vessels were thickened by proliferation of the medial and adventitia layers. At 8
      weeks, we found fibrosis in the subchondral bone with thinned and devitalized
      angiogenesis fat areas. The articular cartilage showed irregularities. At 12
      weeks the closure of the physis was noted, as well as chondral areas in the
      trabecular bone and fat cells in the methaphysis. CONCLUSION: Although the
      histological changes are consistent with necrosis of the femoral head, the images
      obtained did not resemble Perthes disease, so we do not advise this experimental
      model for the study of this disease.

PMID- 24439852
TI  - Predictive ability of metabolic syndrome for incident cardiovascular disease in
      non-diabetic subjects.

PMID- 24439853
TI  - Vascular endothelial growth factor polymorphisms and coronary artery disease: a
      systemic review and meta-analysis.

PMID- 24439854
TI  - An absence of atherosclerosis progression in a type 2 diabetic patient with
      multiple atherosclerotic risk factors, complicated with liver cirrhosis.

PMID- 24439855
TI  - Left atrial wall thickness rather than epicardial fat thickness is related to
      complex fractionated atrial electrogram.

PMID- 24439856
TI  - Primary PCI or pharmaco-invasive strategy in ST-segment elevation myocardial
      infarction.

PMID- 24439857
TI  - Olfactory non-cancer effects of exposure to ionizing radiation in staff working
      in the cardiac catheterization laboratory.

PMID- 24439858
TI  - Mitral valve-sparing resection of huge left ventricle cardiac fibroma.

PMID- 24439859
TI  - Left ventricular hypertrabeculation/noncompaction and pregnancy.

PMID- 24439860
TI  - Transcatheter aortic valve implantation in a patient with severe native aortic
      regurgitation after infective endocarditis.

PMID- 24439861
TI  - High dose statins should be used in all patients undergoing percutaneous coronary
      intervention.

PMID- 24439862
TI  - Cell persistence and electrical integration of transplanted fetal cardiomyocytes
      from different developmental stages.

PMID- 24439863
TI  - Effects of eplerenone on P-wave signal-averaged electrocardiogram in hypertensive
      patients with coronary artery disease.

PMID- 24439864
TI  - Cilostazol enhances mobilization and proliferation of endothelial progenitor
      cells and collateral formation by modifying vasculo-angiogenic biomarkers in
      peripheral arterial disease.

PMID- 24439865
TI  - Electrocardiographic algorithms to predict true right ventricular pacing in the
      presence of right bundle branch block-like pattern.

PMID- 24439866
TI  - Transcatheter renal sympathetic denervation despite angiographically significant
      proximal stenosis: proof of concept from a case report.

PMID- 24439867
TI  - Morphological-biohumoral correlations in acute coronary syndromes: pathogenetic
      implications.

PMID- 24439868
TI  - Alignment of United States funding for cardiovascular disease research with
      deaths, years of life lost, and hospitalizations.

PMID- 24439869
TI  - Recurrent stroke and myocardial infarction in a young woman with severe
      osteoporosis and hyperparathyroidism.

PMID- 24439870
TI  - There is a need for independent studies about new oral anticoagulants in atrial
      fibrillation patients.

PMID- 24439871
TI  - False-positive findings in 320-slice cardiac CT for detection of severe coronary
      stenosis in comparison with invasive coronary angiography indicate poor prognosis
      for occurrence of MACE.

PMID- 24439872
TI  - Self-rated health, beta-blockers and adverse events.

PMID- 24439873
TI  - NLRP1 inflammasome, and not NLRP3, is the key in the shift to proinflammatory
      state on endothelial cells in peripheral arterial disease.

PMID- 24439874
TI  - Confounding factors in the relation between high sensitivity cardiac troponin T
      levels in serum and infarct size of patients with first ST-elevation myocardial
      infarction.

PMID- 24439876
TI  - Otitis externa.
AB  - Acute otitis externa (AOE) is most often infectious in origin, and can be easily
      treated with a combination of topical antibiotic and steroid preparations.
      Systemic antibiotics are rarely needed for AOE. Chronic otitis externa (COE) can
      be more difficult to treat, but if an underlying cause can be identified this
      condition can often be successfully managed. In both AOE and COE, prevention is
      fundamental. If patients are able to avoid precipitating factors, future episodes
      can often be averted. 

PMID- 24439877
TI  - Acute otitis media.
AB  - One in 4 children will have at least 1 episode of acute otitis media (AOM) by age
      10 years. AOM results from infection of fluid that has become trapped in the
      middle ear. The bacteria that most often cause AOM are Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis. Differentiating AOM from
      otitis media with effusion (OME) is a critical skill for physicians, as accurate
      diagnosis will guide appropriate treatment of these conditions. Although fluid is
      present in the middle ear in both conditions, the fluid is not infected in OME as
      is seen in AOM patients. 

PMID- 24439875
TI  - ABCC9 is a novel Brugada and early repolarization syndrome susceptibility gene.
AB  - BACKGROUND: Genetic defects in KCNJ8, encoding the Kir6.1 subunit of the ATP
      sensitive K(+) channel (I(K-ATP)), have previously been associated with early
      repolarization (ERS) and Brugada (BrS) syndromes. Here we test the hypothesis
      that genetic variants in ABCC9, encoding the ATP-binding cassette transporter of
      IK-ATP (SUR2A), are also associated with both BrS and ERS. METHODS AND RESULTS:
      Direct sequencing of all ERS/BrS susceptibility genes was performed on 150
      probands and family members. Whole-cell and inside-out patch-clamp methods were
      used to characterize mutant channels expressed in TSA201-cells. Eight ABCC9
      mutations were uncovered in 11 male BrS probands. Four probands, diagnosed with
      ERS, carried a highly-conserved mutation, V734I-ABCC9. Functional expression of
      the V734I variant yielded a Mg-ATP IC50 that was 5-fold that of wild-type (WT).
      An 18-y/o male with global ERS inherited an SCN5A-E1784K mutation from his
      mother, who displayed long QT intervals, and S1402C-ABCC9 mutation from his
      father, who displayed an ER pattern. ABCC9-S1402C likewise caused a gain of
      function of IK-ATP with a shift of ATP IC50 from 8.5 +/- 2 mM to 13.4 +/- 5 MUM
      (p<0.05). The SCN5A mutation reduced peak INa to 39% of WT (p<0.01), shifted
      steady-state inactivation by -18.0 mV (p<0.01) and increased late I(Na) from
      0.14% to 2.01% of peak I(Na) (p<0.01). CONCLUSION: Our study is the first to
      identify ABCC9 as a susceptibility gene for ERS and BrS. Our findings also
      suggest that a gain-of-function in I(K-ATP) when coupled with a loss-of-function
      in SCN5A may underlie type 3 ERS, which is associated with a severe arrhythmic
      phenotype.

PMID- 24439878
TI  - Hearing loss: diagnosis and management.
AB  - Hearing loss may affect all age groups from the newborn to the elderly, impacting
      speech and language development in children and causing social and vocational
      problems for adults. Hearing loss can arise from anywhere in the auditory circuit
      including the external auditory canal, sound conduction mechanism, cochlea,
      cochlear nerve, and central auditory pathways. Rehabilitation options exist for
      all types of hearing loss, regardless of cause or location within the auditory
      system. Awareness of symptoms, signs, and rehabilitative measures aids primary
      care physicians in early identification and treatment of hearing loss. 

PMID- 24439879
TI  - Rhinitis.
AB  - Rhinitis is caused by a variety of allergic and nonallergic mechanisms. Mild
      disease can usually be managed with avoidance measures alone. Allergen removal
      can also improve the severity of allergic rhinitis and can reduce the need for
      medications. Allergic rhinitis is represented by sneezing, nasal congestion,
      nasal pruritus, and rhinorrhea. Oral antihistamines should be used to treat
      patients with mild or occasional seasonal allergic rhinitis. Because of the
      variance in causes of nonallergic rhinitis, treatments also vary. Irrigation and
      debridement are the standard treatment of atrophic rhinitis. For gustatory
      rhinitis, pretreatment with ipratropium bromide can be used. 

PMID- 24439881
TI  - Epistaxis: evaluation and treatment.
AB  - Epistaxis, or nosebleed, is a common disorder that many patients will experience.
      Most patients go to the emergency room when they have an uncontrolled nosebleed,
      or they may present to an outpatient office. Most nosebleeds are not life
      threatening and can be managed conservatively. Occasionally, hospital admission,
      referral to an otolaryngologist physician, and/or blood transfusion may be
      necessary. This article is an update on the latest information related to the
      prevention, causes, and treatment of epistaxis. 

PMID- 24439880
TI  - Rhinosinusitis.
AB  - Although sinusitis is common, controversy exists regarding terminology,
      diagnostic criteria, indications for imaging, and treatment guidelines. Patients
      who are diagnosed with bacterial sinusitis should be started on amoxicillin
      clavulanate unless an allergy to penicillin is reported, in which case
      doxycycline or a respiratory fluoroquinolone is indicated for non-pregnant
      patients. Patients who fail to respond to antibiotic therapy should be suspected
      of having chronic sinusitis, which may requirea dditional therapy, including
      endoscopic surgery. Referral of these patients to an otolaryngologist for further
      evaluation is recommended. Patients with severe systemic symptoms including
      altered mental status or severe headaches should be suspected of having fungal
      sinusitis and to an otolaryngologist acutely because this condition has high
      mortality if not treated emergently. 

PMID- 24439882
TI  - Diseases of the mouth.
AB  - Oral pathologic abnormality is common and can be potentially serious. There are
      many diseases of the mouth that medical personnel must be able to diagnose and
      initiate management. The most prevalent lesions can be categorized as infectious,
      inflammatory, and common benign and malignant lesions. This article discusses
      prevalence, cause, diagnosis, and management of lesions such as stomatitis,
      candidiasis, caries, oral cancers, and bony tori. 

PMID- 24439883
TI  - Pharyngitis.
AB  - Most infectious pharyngitis has a viral cause. The use of aspirin or nonsteroidal
      antiinflammatory agents (NSAIAs) is advised in adults and NSAIAs in children for
      the treatment of pain. There are several studies that show that NSAIAs relieve
      pharyngitis pain better than acetaminophen. Penicillin remains the antibiotic of
      choice of group A beta-hemolytic streptococcal (GAS) pharyngitis. Resistance has
      not developed to penicillin. Patients with GAS pharyngitis should have
      improvement in 3 to 4 days. If not better at that time, the patient should be
      seen for diagnostic reconsideration or the development of a suppurative
      complication. 

PMID- 24439884
TI  - Laryngeal problems.
AB  - Laryngeal complaints are common reasons for patients to seek care. There is
      considerable overlap between patient symptoms and final diagnosis. This article
      begins with a general approach to laryngeal symptoms followed by individual
      consideration of both the common and serious conditions of the larynx. Early
      diagnosis and treatment are important for improving outcomes in patients with
      laryngeal complaints. 

PMID- 24439885
TI  - Nasolaryngoscopy.
AB  - Nasolaryngoscopy is a low-risk, quick means of making a specific diagnosis for
      voice complaints; it should be performed before empiric treatment based on
      history and general examination alone. The most common indications for
      nasolaryngoscopy are hoarseness, globus sensation, and chronic cough. The most
      common findings in a primary care setting include laryngopharyngeal reflux (43%),
      chronic rhinitis (32%), and vocal cord lesions (13%). 

PMID- 24439886
TI  - Dizziness and vertigo.
AB  - Dizziness is a common and challenging condition seen in the primary care office.
      Because dizziness is a vague term that can include a wide array of medical
      disorders, it is important to use a stepwise approach to differentiate between
      causes. This article focuses on vertigo and its four most common causes: benign
      paroxysmal peripheral vertigo, vestibular neuritis, vestibular migraine, and
      Meniere's disease. 

PMID- 24439887
TI  - Neurologic syndromes of the head and neck.
AB  - Although patients with Bell palsy and trigeminal neuralgia occasionally present
      to primary care physicians, most of the syndromes in this article are somewhat
      rare in primary care practice. It is important to recognize signs and symptoms of
      these syndromes so that appropriate management is carried out. Patients may
      experience sensory and/or motor symptoms of the head and neck due to disorders of
      the cranial and cervical nerves. The syndromes and symptoms discussed in this
      article include ear pain, sinus pain, herpes zoster (HZ) oticus (Ramsay Hunt), HZ
      ophthalmicus, facial nerve paralysis in adults and children, superior laryngeal
      neuralgia, trigeminal neuralgia, glossopharyngeal neuralgia, nervus intermedius
      (geniculate) neuralgia, and Raeder paratrigeminal syndrome. 

PMID- 24439888
TI  - Drips, plugs, and scratches. Foreword.

PMID- 24439890
TI  - The operating surgeon is an independent predictor of chest tube drainage
      following cardiac surgery.
AB  - OBJECTIVES: Bleeding into the chest is a major cause of blood transfusion and
      adverse outcomes following cardiac surgery. The authors investigated predictors
      of bleeding following cardiac surgery to identify potentially correctable
      factors. DESIGN: Data were retrieved from the medical records of patients
      undergoing cardiac surgery over the period of 2002 to 2008. Multivariate analysis
      was used to identify the independent predictors of chest tube drainage. SETTING:
      Tertiary hospital. PARTICIPANTS: Two thousand five hundred seventy-five patients.
      INTERVENTIONS: Cardiac surgery. RESULTS: The individual operating surgeon was
      independently associated with the extent of chest tube drainage. Other
      independent factors included internal mammary artery grafting, cardiopulmonary
      bypass time, urgency of surgery, tricuspid valve surgery, redo surgery, left
      ventricular impairment, male gender, lower body mass index and higher
      preoperative hemoglobin levels. Both a history of diabetes and administration of
      aprotinin were associated with reduced levels of chest tube drainage.
      CONCLUSIONS: The individual operating surgeon was an independent predictor of the
      extent of chest tube drainage. Attention to surgeon-specific factors offers the
      possibility of reduced bleeding, fewer transfusions, and improved patient
      outcomes.

PMID- 24439891
TI  - Mycobacterial lipid logic.
AB  - During infection of the lung epithelium, Mycobacterium tuberculosis must infect
      and survive within macrophages long enough to be transported into deeper lung
      tissues. Cambier et al. (2013) show that pathogenic mycobacteria use the
      coordinated action of two cell wall glycolipids to regulate macrophage
      recruitment to initial infection sites. 

PMID- 24439892
TI  - InFLUencing host survival: cIAP2 tips the scales.
AB  - Necroptosis has emerged as an important facet of both host defense and
      inflammatory disease. In this issue, Rodrigue-Gervais et al. (2014) demonstrate a
      role for the cell death regulator cIAP2 in maintaining lung homeostasis during
      influenza infection. Loss of cIAP2 promotes necroptosis of lung tissues, leading
      to host death. 

PMID- 24439893
TI  - Gut microbes take their vitamins.
AB  - The dense microbial ecosystem within the gut is connected through a complex web
      of metabolic interactions. In this issue of Cell Host & Microbe, Degnan et al.
      (2014) establish the importance of different vitamin B12 transporters that help a
      Bacteroides species acquire vitamins from the environment to maintain a
      competitive edge. 

PMID- 24439894
TI  - Phagocyte roulette in Salmonella killing.
AB  - Salmonella propagates in macrophages to cause life-threatening infections, but
      the role of neutrophils in combating Salmonella has been controversial. In this
      issue, Burton et al. (2014) use single cell analyses and modeling to explain the
      ability of Salmonella to survive in macrophages while being killed by
      neutrophils. 

PMID- 24439895
TI  - Cellular inhibitor of apoptosis protein cIAP2 protects against pulmonary tissue
      necrosis during influenza virus infection to promote host survival.
AB  - Cellular inhibitors of apoptosis proteins (cIAPs) are essential regulators of
      cell death and immunity. The corresponding contributions of IAPs to infectious
      disease outcomes are relatively unexplored. We find that mice deficient in cIAP2
      exhibit increased susceptibility and mortality to influenza A virus infection.
      The lethality was not due to impaired antiviral immune functions, but rather
      because of death-receptor-induced programmed necrosis of airway epithelial cells
      that led to severe bronchiole epithelial degeneration, despite control of viral
      replication. Pharmacological inhibition of RIPK1 or genetic deletion of Ripk3,
      both kinases involved in programmed necrosis, rescued cIAP2-deficient mice from
      influenza-induced lethality. Genetic deletion of the death receptor agonists Fas
      ligand or TRAIL from the hematopoietic compartment also reversed the
      susceptibility of cIAP2-deficient mice. Thus, cIAP2-dependent antagonism of RIPK3
      mediated programmed necrosis critically protects the host from influenza
      infection through maintenance of pulmonary tissue homeostasis rather than through
      pathogen control by the immune system. 

PMID- 24439896
TI  - Bacterial lipopolysaccharide binding enhances virion stability and promotes
      environmental fitness of an enteric virus.
AB  - Enteric viruses, including poliovirus and reovirus, encounter a vast microbial
      community in the mammalian gastrointestinal tract, which has been shown to
      promote virus replication and pathogenesis. Investigating the underlying
      mechanisms, we find that poliovirus binds bacterial surface polysaccharides,
      which enhances virion stability and cell attachment by increasing binding to the
      viral receptor. Additionally, we identified a poliovirus mutant, VP1-T99K, with
      reduced lipopolysaccharide (LPS) binding. Although T99K and WT poliovirus cell
      attachment, replication, and pathogenesis in mice are equivalent, VP1-T99K
      poliovirus was unstable in feces following peroral inoculation of mice.
      Consequently, the ratio of mutant virus in feces is reduced following additional
      cycles of infection in mice. Thus, the mutant virus incurs a fitness cost when
      environmental stability is a factor. These data suggest that poliovirus binds
      bacterial surface polysaccharides, enhancing cell attachment and environmental
      stability, potentially promoting transmission to a new host.

PMID- 24439897
TI  - Human gut microbes use multiple transporters to distinguish vitamin B12 analogs
      and compete in the gut.
AB  - Genomic and metagenomic sequencing efforts, including human microbiome projects,
      reveal that microbes often encode multiple systems that appear to accomplish the
      same task. Whether these predictions reflect actual functional redundancies is
      unclear. We report that the prominent human gut symbiont Bacteroides
      thetaiotaomicron employs three functional, homologous vitamin B12 transporters
      that in at least two cases confer a competitive advantage in the presence of
      distinct B12 analogs (corrinoids). In the mammalian gut, microbial fitness can be
      determined by the presence or absence of a single transporter. The total number
      of distinct corrinoid transporter families in the human gut microbiome likely
      exceeds those observed in B. thetaiotaomicron by an order of magnitude. These
      results demonstrate that human gut microbes use elaborate mechanisms to capture
      and differentiate corrinoids in vivo and that apparent redundancies observed in
      these genomes can instead reflect hidden specificities that determine whether a
      microbe will colonize its host.

PMID- 24439898
TI  - Gut microbiota of the tick vector Ixodes scapularis modulate colonization of the
      Lyme disease spirochete.
AB  - Arthopods such as Ixodes scapularis ticks serve as vectors for many human
      pathogens. The arthropod gut presents a pivotal microbial entry point and
      determines pathogen colonization and survival. We show that the gut microbiota of
      I. scapularis, a major vector of the Lyme disease spirochete Borrelia
      burgdorferi, influence spirochete colonization of ticks. Perturbing the gut
      microbiota of larval ticks reduced Borrelia colonization, and dysbiosed larvae
      displayed decreased expression of the transcription factor signal transducer and
      activator of transcription (STAT). Diminished STAT expression corresponded to
      lower expression of peritrophin, a key glycoprotein scaffold of the glycan-rich
      mucus-like peritrophic matrix (PM) that separates the gut lumen from the
      epithelium. The integrity of the I. scapularis PM was essential for B.
      burgdorferi to efficiently colonize the gut epithelium. These data elucidate a
      functional link between the gut microbiota, STAT-signaling, and pathogen
      colonization in the context of the gut epithelial barrier of an arthropod vector.

PMID- 24439899
TI  - Disparate impact of oxidative host defenses determines the fate of Salmonella
      during systemic infection in mice.
AB  - Reactive oxygen and nitrogen species function in host defense via mechanisms that
      remain controversial. Pathogens might encounter varying levels of these species,
      but bulk measurements cannot resolve such heterogeneity. We used single-cell
      approaches to determine the impact of oxidative and nitrosative stresses on
      individual Salmonella during early infection in mouse spleen. Salmonella
      encounter and respond to both stresses, but the levels and impact vary widely.
      Neutrophils and inflammatory monocytes kill Salmonella by generating overwhelming
      oxidative stress through NADPH oxidase and myeloperoxidase. This controls
      Salmonella within inflammatory lesions but does not prevent their spread to more
      permissive resident red pulp macrophages, which generate only sublethal oxidative
      bursts. Regional host expression of inducible nitric oxide synthase exposes some
      Salmonella to nitrosative stress, triggering effective local Salmonella
      detoxification through nitric oxide denitrosylase. Thus, reactive oxygen and
      nitrogen species influence dramatically different outcomes of disparate
      Salmonella-host cell encounters, which together determine overall disease
      progression.

PMID- 24439900
TI  - Mechanisms underlying robustness and tunability in a plant immune signaling
      network.
AB  - The plant immune signaling network needs to be robust against attack from fast
      evolving pathogens and tunable to optimize immune responses. We investigated the
      basis of robustness and tunability in the signaling network controlling pattern
      triggered immunity (PTI) in Arabidopsis. A dynamic network model containing four
      major signaling sectors, the jasmonate, ethylene, phytoalexin-deficient 4, and
      salicylate sectors, which together govern up to 80% of the PTI levels, was built
      using data for dynamic sector activities and PTI levels under exhaustive
      combinatorial sector perturbations. Our regularized multiple regression model had
      a high level of predictive power and captured known and unexpected signal flows
      in the network. The sole inhibitory sector in the model, the ethylene sector,
      contributed centrally to network robustness via its inhibition of the jasmonate
      sector. The model's multiple input sites linked specific signal input patterns
      varying in strength and timing to different network response patterns, indicating
      a mechanism enabling tunability. 

PMID- 24439902
TI  - siRNA screen of early poxvirus genes identifies the AAA+ ATPase D5 as the virus
      genome-uncoating factor.
AB  - Poxvirus genome uncoating is a two-step process. First, cytoplasmic viral cores
      are activated and early viral genes are expressed. Next, cores are disassembled
      and the genomes released. This second step depends on an early viral factor(s)
      that has eluded identification for over 40 years. We used a large-scale, high
      throughput RNAi screen directed against vaccinia virus (VACV) to identify the
      VACV AAA+ ATPase D5 as the poxvirus uncoating factor. We show that the ATPase
      activity of D5 is required for uncoating. Superresolution microscopy suggests
      that D5 acts directly at viral cores for genome release. Thus, the putative
      helicase D5 is a multifunctional protein required for genome uncoating and
      replication. Additionally, in vivo delivery of anti-D5 siRNAs reduced virus
      production in a mouse model of VACV infection. These results demonstrate the use
      of virus-targeting RNAi libraries to investigate viral gene function and suggest
      therapeutic avenues.

PMID- 24439901
TI  - Gut dysbiosis promotes M2 macrophage polarization and allergic airway
      inflammation via fungi-induced PGE2.
AB  - Although imbalances in gut microbiota composition, or "dysbiosis," are associated
      with many diseases, the effects of gut dysbiosis on host systemic physiology are
      less well characterized. We report that gut dysbiosis induced by antibiotic (Abx)
      treatment promotes allergic airway inflammation by shifting macrophage
      polarization in the lung toward the alternatively activated M2 phenotype.
      Adoptive transfer of alveolar macrophages derived from Abx-treated mice was
      sufficient to increase allergic airway inflammation. Abx treatment resulted in
      the overgrowth of a commensal fungal Candida species in the gut and increased
      plasma concentrations of prostaglandin E2 (PGE2), which induced M2 macrophage
      polarization in the lung. Suppression of PGE2 synthesis by the cyclooxygenase
      inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and
      decreased allergic airway inflammatory cell infiltration in Abx-treated mice.
      Thus, Abx treatment can cause overgrowth of particular fungal species in the gut
      and promote M2 macrophage activation at distant sites to influence systemic
      responses including allergic inflammation.

PMID- 24439904
TI  - Sema4A inhibits the therapeutic effect of IFN-beta in EAE.
AB  - Approximately one-third of patients with multiple sclerosis (MS) respond poorly
      to interferon-beta (IFN-beta) therapy. Serum Sema4A is increased in MS patients,
      and those who have high Sema4A do not respond to IFN-beta therapy. In this study,
      we investigated whether recombinant Sema4A abrogates the efficacy of IFN-beta in
      mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
      Administration of Sema4A concurrently with IFN-beta diminished the efficacy of
      IFN-beta in EAE. These effects of Sema4A were attributed to promote Th1 and Th17
      differentiation and to increase adhesive activation of T cells to endothelial
      cells, even in the presence of IFN-beta. 

PMID- 24439903
TI  - Chlamydia trachomatis-induced alterations in the host cell proteome are required
      for intracellular growth.
AB  - Intracellular pathogens directly alter host cells in order to replicate and
      survive. While infection-induced changes in host transcription can be readily
      assessed, posttranscriptional alterations are more difficult to catalog. We
      applied the global protein stability (GPS) platform, which assesses protein
      stability based on relative changes in an adjoining fluorescent tag, to identify
      changes in the host proteome following infection with the obligate intracellular
      bacteria Chlamydia trachomatis. Our results indicate that C. trachomatis
      profoundly remodels the host proteome independently of changes in transcription.
      Additionally, C. trachomatis replication depends on a subset of altered proteins,
      such as Pin1 and Men1, that regulate the host transcription factor AP-1
      controlling host inflammation, stress, and cell survival. Furthermore, AP-1
      dependent transcription is activated during infection and required for efficient
      Chlamydia growth. In summary, this experimental approach revealed that C.
      trachomatis broadly alters host proteins and can be applied to examine host
      pathogen interactions and develop host-based therapeutics. 

PMID- 24439905
TI  - Steroids for surgery during cardiopulmonary bypass in adults: a meta-analysis.
AB  - STUDY OBJECTIVE: To evaluate the effect of steroid administration on myocardial
      infarction (MI), stroke, renal insufficiency, death, intensive care (ICU) length
      of stay (LOS) and hospital LOS of patients undergoing cardiopulmonary bypass
      (CPB). DESIGN: Meta-analysis of parallel randomized controlled trials. SETTING:
      University hospital. MEAUREMENTS: A search was conducted in PubMed, EMBASE,
      MEDLINE(R) and the Cochrane Central Register of Controlled Trials of studies on
      adults undergoing surgery with CPB who received steroid administration. Effect
      size (risk ratio or mean difference) for MI, stroke, renal insufficiency, death,
      ICU LOS, and hospital LOS were evaluated. MAIN RESULTS: 48 RCTs published between
      1977 and 2012 were retained for analysis. Steroids had no effect on the MI risk
      ratio (RR) 0.91 (95% confidence interval [CI] 0.63, 1.32); death at 30 days RR
      0.84 (0.59, 1.20); stroke RR 0.92 (0.60, 1.42) or renal insufficiency RR 0.83
      (0.52, 1.32). Administration of steroids reduced ICU LOS (P = 0.00001; I(2)
      87.5%) and hospital LOS (P = 0.03; I(2) 81.1%). Metaregressions showed that
      duration of steroid administration was correlated with the reduction in ICU LOS
      (P = 0.0004) and hospital LOS (P < 0.00001). CONCLUSIONS: Increasing the duration
      of steroid administration may reduce ICU and hospital LOS greater than increasing
      the dose.

PMID- 24439906
TI  - Misplacement of a right internal jugular hemodialysis catheter in a persistent
      left superior vena cava.

PMID- 24439910
TI  - Functional diversification of Dicer-like proteins and small RNAs required for
      genome sculpting.
AB  - In eukaryotes, small RNAs (sRNAs) have key roles in development, gene expression
      regulation, and genome integrity maintenance. In ciliates, such as Paramecium,
      sRNAs form the heart of an epigenetic system that has evolved from core
      eukaryotic gene silencing components to selectively target DNA for deletion. In
      Paramecium, somatic genome development from the germline genome accurately
      eliminates the bulk of typically gene-interrupting, noncoding DNA. We have
      discovered an sRNA class (internal eliminated sequence [IES] sRNAs [iesRNAs]),
      arising later during Paramecium development, which originates from and precisely
      delineates germline DNA (IESs) and complements the initial sRNAs ("scan" RNAs
      [scnRNAs]) in targeting DNA for elimination. We show that whole-genome
      duplications have facilitated successive differentiations of Paramecium Dicer
      like proteins, leading to cooperation between Dcl2 and Dcl3 to produce scnRNAs
      and to the production of iesRNAs by Dcl5. These innovations highlight the ability
      of sRNA systems to acquire capabilities, including those in genome development
      and integrity. 

PMID- 24439912
TI  - Kinetics analysis for development of a rate constant estimation model for
      ultrasonic degradation reaction of methylene blue.
AB  - Ultrasound has been used as an advanced oxidation method for wastewater
      treatment. Sonochemical degradation of organic compounds in aqueous solution
      occurs by pyrolysis and/or reaction with hydroxyl radicals. Moreover, kinetics of
      sonochemical degradation has been proposed. However, the effect of ultrasonic
      frequency on degradation rate has not been investigated. In our previous study, a
      simple model for estimating the apparent degradation rate of methylene blue was
      proposed. In this study, sonochemical degradation of methylene blue was performed
      at various frequencies. Apparent degradation rate constant was evaluated assuming
      that sonochemical degradation of methylene blue was a first-order reaction.
      Specifically, we focused on effects of ultrasonic frequency and power on rate
      constant, and the applicability of our proposed model was demonstrated. Using
      this approach, maximum sonochemical degradation rate was observed at 490 kHz,
      which agrees with a previous investigation into the effect of frequency on the
      sonochemical efficiency value evaluated by KI oxidation dosimetry. Degradation
      rate increased with ultrasonic power at every frequency. It was also observed
      that threshold power must be reached for the degradation reaction to progress.
      The initial methylene blue concentration and the apparent degradation rate
      constant have a relation of an inverse proportion. Our proposed model for
      estimating the apparent degradation rate constant using ultrasonic power and
      sonochemical efficiency value can apply to this study which extended the
      frequency and initial concentration range.

PMID- 24439911
TI  - Stress-induced nuclear-to-cytoplasmic translocation of cyclin C promotes
      mitochondrial fission in yeast.
AB  - Mitochondrial morphology is maintained by the opposing activities of dynamin
      based fission and fusion machines. In response to stress, this balance is
      dramatically shifted toward fission. This study reveals that the yeast
      transcriptional repressor cyclin C is both necessary and sufficient for stress
      induced hyperfission. In response to oxidative stress, cyclin C translocates from
      the nucleus to the cytoplasm, where it is destroyed. Prior to its destruction,
      cyclin C both genetically and physically interacts with Mdv1p, an adaptor that
      links the GTPase Dnm1p to the mitochondrial receptor Fis1p. Cyclin C is required
      for stress-induced Mdv1p mitochondrial recruitment and the efficient formation of
      functional Dnm1p filaments. Finally, coimmunoprecipitation studies and
      fluorescence microscopy revealed an elevated association between Mdv1p and Dnm1p
      in stressed cells that is dependent on cyclin C. This study provides a mechanism
      by which stress-induced gene induction and mitochondrial fission are coordinated
      through translocation of cyclin C. 

PMID- 24439913
TI  - Process optimization of ultrasound-assisted curcumin nanoemulsions stabilized by
      OSA-modified starch.
AB  - This study reports on the process optimization of ultrasound-assisted, food-grade
      oil-water nanoemulsions stabilized by modified starches. In this work, effects of
      major emulsification process variables including applied power in terms of power
      density and sonication time, and formulation parameters, that is, surfactant type
      and concentration, bioactive concentration and dispersed-phase volume fraction
      were investigated on the mean droplet diameter, polydispersity index and charge
      on the emulsion droplets. Emulsifying properties of octenyl succinic anhydride
      modified starches, that is, Purity Gum 2000, Hi-Cap 100 and Purity Gum Ultra, and
      the size stability of corresponding emulsion droplets during the 1 month storage
      period were also investigated. Results revealed that the smallest and more stable
      nanoemulsion droplets were obtained when coarse emulsions treated at 40% of
      applied power (power density: 1.36 W/mL) for 7 min, stabilized by 1.5% (w/v)
      Purity Gum Ultra. Optimum volume fraction of oil (medium chain triglycerides) and
      the concentration of bioactive compound (curcumin) dispersed were 0.05 and 6
      mg/mL oil, respectively. These results indicated that the ultrasound-assisted
      emulsification could be successfully used for the preparation of starch
      stabilized nanoemulsions at lower temperatures (40-45  degrees C) and reduced
      energy consumption.

PMID- 24439914
TI  - Clinical Practice Statements and the American Academy of Oral Medicine.

PMID- 24439915
TI  - A simple test for salivary gland function measuring resting and stimulated
      submandibular and sublingual secretions.
AB  - OBJECTIVE: This study examined the application of a simple screening test for
      salivary gland function by measuring resting and stimulated submandibular and
      sublingual secretions. STUDY DESIGN: An assay system was designed to use filter
      paper incorporating the chromophore of melanoidin or stimuli such as capsaicin
      and citric acid. We investigated the relationship between resting and stimulated
      secretions and melanoidin migration at 2 minutes for healthy and dry mouth
      groups. RESULTS: The healthy group showed a significant increase in the migration
      of melanoidin in the paper after citric acid or capsaicin stimulation. In
      contrast, patients with Sjogren syndrome showed no significant migration in spite
      of the stimulation. However, some participants with Sjogren syndrome or dry mouth
      showed a significant increase in the migration of melanoidin after stimulation.
      CONCLUSIONS: These results show that the newly developed method should be useful
      for evaluation of residual salivary gland function and screening for
      hyposalivation with dry mouth.

PMID- 24439917
TI  - Dendritic cell neurofibroma with pseudorosettes: a clinicopathologic and
      immunohistochemical study of 5 intraoral cases.
AB  - OBJECTIVE: We report cases of dendritic cell neurofibroma with pseudorosettes
      (DCNP) presenting in the oral cavity and discuss clinicopathologic and
      immunohistochemical features that differentiate this from other benign peripheral
      nerve sheath tumors. STUDY DESIGN: DCNPs were identified over a 2-year period,
      and history and histopathologic features were reviewed. Common nerve sheath
      tumors from the same period were identified and compared. RESULTS: Five intraoral
      cases of DCNP presented in 2 men and 3 women, with a median age of 59 years.
      Three presented on the buccal mucosa, and 2 presented on the tongue. Each
      exhibited a biphasic population of cells with pseudorosettes and strong CD57
      positivity. CONCLUSIONS: With 31 cases of DCNP reported, the most common site of
      occurrence is now the head and neck region. DCNPs exhibit a characteristic
      biphasic population of cells and strong CD57 positivity. Pathologists should
      consider this diagnosis when confronted with unusual neural lesions.

PMID- 24439916
TI  - Impact of apigenin and kaempferol on human head and neck squamous cell carcinoma.
AB  - OBJECTIVE: Apigenin and kaempferol are plant flavonoids with reported
      chemopreventive activities. This study aimed to determine the effect of apigenin
      and kaempferol on cell viability in cultured cells derived from the pharynx (FaDu
      cell line), an oral cavity carcinoma (PCI-13 cell line), and a metastatic lymph
      node (PCI-15B cell line) and in explanted FaDu cells. STUDY DESIGN: The in vitro
      viability of FaDu, PCI-13, and PCI-15B cells treated with apigenin and kaempferol
      was determined. Tumor growth of FaDu explants was evaluated in athymic mice that
      were gavaged with either apigenin or kaempferol. RESULTS: Although apigenin and
      kaempferol treatment decreased viability of cells in vitro, cell-type-dependent
      differences in responsiveness were observed. In vivo apigenin treatment
      significantly increased the tumor size of FaDu explants. Results obtained using
      kaempferol were similar. CONCLUSIONS: The in vitro decrease in FaDu cell
      viability by apigenin and kaempferol was not observed in in vivo tumor explants
      using the conditions described in this study.

PMID- 24439918
TI  - Upregulation of a potential prognostic biomarker, miR-155, enhances cell
      proliferation in patients with oral squamous cell carcinoma.
AB  - OBJECTIVE: We sought to investigate the role and diagnostic value of microRNA 155
      (miR-155) in OSCC patients. STUDY DESIGN: Using real-time quantitative polymerase
      chain reaction analysis, miR-155 expression levels were assessed in OSCC cell
      lines and a cancerous HB cell line. The correlation between miR-155 expression
      level and clinical parameters was analyzed in 46 patients with OSCC. In addition,
      the effects of miR-155 on OSCC cell proliferation were evaluated by modulating
      its expression using an miR-155 mimic and antisense miR-155. RESULTS: Significant
      upregulation of miR-155 was found in OSCC cell lines and in tissues of patients
      with OSCC. The receiver operator characteristic analysis indicated fair-to-good
      predictability. Overexpression of miR-155 correlated with the histologic grade (P
      = .033), and the upregulation of miR-155 enhanced OSCC cell proliferation.
      CONCLUSIONS: In OSSC, upregulation of miR-155 correlated with the histologic
      grade and can be used as a potential prognostic biomarker.

PMID- 24439919
TI  - Upregulation of Src homology phosphotyrosyl phosphatase 2 (Shp2) expression in
      oral cancer and knockdown of Shp2 expression inhibit tumor cell viability and
      invasion in vitro.
AB  - OBJECTIVE: This study investigated the clinical significance of Shp2 protein
      expression in oral squamous cell carcinoma (OSCC) and elucidated its biologic
      significance in OSCC cells. STUDY DESIGN: A total of 88 OSCC cases were used to
      assess Shp2 expression, out of which 70 were for immunohistochemistry and 18
      paired tumors vs normal tissues were for Western blot of Shp2 expression. OSCC
      cells were used to assess the effects of Shp2 knockdown for cell viability,
      apoptosis, invasion, and protein expressions. RESULTS: Expression of Shp2 protein
      was significantly upregulated in OSCC tissues compared with the normal tissues,
      and Shp2 overexpression was associated with advanced tumor clinical stages and
      lymph node metastasis ex vivo. Knockdown of Shp2 expression in vitro inhibited
      OSCC cell viability and invasion but induced apoptosis by regulating expression
      of the apoptosis-related proteins. CONCLUSIONS: The data indicated that Shp2 may
      play an important role in OSCC progression. Further studies will investigate
      whether a target of Shp2 expression could be a novel therapeutic strategy for
      clinical control of OSCC.

PMID- 24439920
TI  - Classification and characteristics of pterygoid process fracture associated with
      maxillary transverse fracture.
AB  - OBJECTIVE: This study aimed to classify pterygoid process fractures associated
      with maxillary transverse fractures. STUDY DESIGN: Pterygoid process fractures in
      100 patients with maxillary transverse fractures were observed 2- and 3
      dimensionally using image processing software. Fracture line course and height
      and sphenoid sinus involvement were recorded. RESULTS: Pterygoid process
      fractures were classified as follows: class I, vertical (simple separation
      between medial and lateral plates); or class II, transverse (3 subcategories
      according to location of fracture line: II-1, within pterygoid fossa; II-2, above
      pterygoid fossa, not extending to sphenoid sinus floor; II-3, above pterygoid
      fossa, involving sphenoid sinus floor). Class I fracture was observed on 5 sides
      (2.7%); II-1, on 125 (66.5%); II-2, on 36 (19.1%); and II-3, on 22 (1.7%).
      CONCLUSIONS: Pterygoid process fractures were predominantly near the upper edge
      of the pterygoid fossa. Pneumatization of the pterygoid process is a risk in
      fractures involving the sphenoid sinus floor.

PMID- 24439921
TI  - Discrepancies on dexamethasone for trismus after third molar extraction.

PMID- 24439922
TI  - Reply to comments of the article "photodynamic treatment of oral lichen planus".

PMID- 24439923
TI  - Early references to necrotizing sialometaplasia.

PMID- 24439924
TI  - Diffuse large B-cell lymphoma of the mandible with periosteal reaction: a case
      report.
AB  - This report describes a rare case of a 63-year-old man with a lymphoma in the
      right mandibular ramus with periosteal reaction. Computed tomography (CT) images
      showed a soft tissue density (28 * 48 * 32 mm) around the right mandibular
      foramen. Bone-mode CT images showed diffuse bone destruction of the right
      mandibular ramus. Moreover, a periosteal reaction was seen on the lingual
      cortical bone of the right mandibular ramus. Histopathologic examination found a
      diffuse large B-cell lymphoma.

PMID- 24439925
TI  - Prevention or treatment of hypertrophic burn scarring: a review of when and how
      to treat with the pulsed dye laser.
AB  - The purpose of this review is to investigate the use of Pulsed Dye Laser (PDL) as
      a therapeutic tool for hypertrophic burns scarring. The difference between
      keloids and hypertrophic scars is first described. The review then outlines the
      progress and assessment of hypertrophic scars for burns patients and the problem
      of their clinical management. The assessment using both objective and subjective
      measurements for complete account of hypertrophic scars is explained. The
      efficacy of PDL for both prevention and treatment is summarised for all
      hypertrophic scarring and the various laser treatment protocols in previous
      research is studied. The differentiation between prevention and treatment is
      discussed in relation to scar duration and the need for prevention rather than
      treatment is then proposed for intervention using PDL. The paper concludes with
      recommendations for future research through a prospective randomised, controlled
      study using 595 nm PDL in the prevention of scars with less than 6 month
      duration.

PMID- 24439926
TI  - The Chinese language version of the abbreviated burn specific health scale: a
      validation study.
AB  - BACKGROUND: The Burn Specific Health Scale (BSHS) is designed to measure burn
      specific, health-related quality of life (HRQoL). The aim of the present study
      was to evaluate the reliability and validity of the Chinese version of the
      abbreviated BSHS (BSHS-A). METHODS: The English version of the BSHS-A was
      translated into Chinese using a standardised procedure. The participants were 457
      patients classified into three severity groups (mild, moderate and severe). All
      patients completed the Chinese BSHS-A questionnaire, the Short Form-36 (SF-36)
      and the EuroQol 5-Dimensions (EQ-5D). To evaluate clinical utility of the BSHS-A,
      we used Cronbach's alpha (internal consistency), intraclass correlation
      coefficients (ICCs; test-retest reliability) and construct validity (using the SF
      36 and EQ-5D). RESULTS: Cronbach's alpha for all subscales was >0.80,
      demonstrating high internal consistency of the BSHS-A (Chinese version). The ICC
      was >0.70 for each patient group. Strong correlations were observed between the
      BSHS-A and SF-36 and EQ-5D scales. Neither floor nor ceiling effects were found.
      CONCLUSION: The present study demonstrated that the BSHS-A (Chinese version) has
      good psychometric properties, showing suitable internal consistency and test
      retest reliability. The BSHS-A may, thus, be useful for assessing HRQoL in
      Chinese burn victims. However, adaptations may be required to reduce its length.

PMID- 24439927
TI  - Procalcitonin in the burn unit and the diagnosis of infection.
AB  - OBJECTIVE: To determine the usefulness of procalcitonin (PCT) in decision-making
      when faced with suspected infection in patients with extensive burns. STUDY:
      Retrospective, observational follow-up study. INSTITUTION: Burn Unit of the
      Complexo Hospitalario Universitario A Coruna (CHUAC), Spain. PATIENTS AND METHOD:
      We included all patients admitted to the Unit from June 2011 to March 2012 with
      >=20% total body surface area burned or >=10% full-thickness body surface area
      burned with suspected infection (17 patients with 34 events of suspected
      infection). RESULTS: The infections were confirmed in 16/34 episodes (47.1%), and
      documented in 44.1% (n=15). There were no statistically significant differences
      in the PCT figures at the time the infection was suspected between the cases with
      confirmed and unconfirmed infection (p=0.682). The PCT values showed no
      discriminative value for differentiating patients with SIRS from those with
      sepsis, severe sepsis and septic shock (area under ROC curve (AUC)=0.546; 95% CI:
      0.326-0.766). No significant correlation was found between SOFA and PCT, although
      there were differences in the PCT values in the patients who had tissue
      hypoperfusion. CONCLUSION: Results show that PCT is not a precise indicator of
      sepsis at the time of diagnosis. A correlation between PCT levels and
      hypoperfusion was observed.

PMID- 24439928
TI  - Combined crystalline podocytopathy and tubulopathy associated with multiple
      myeloma.
AB  - Lymphoplasmacytic neoplasms cause a wide range of injuries to the kidney
      exemplified by light chain cast nephropathy and amyloidosis. Filtered
      paraproteins can also accumulate within kidney cells and cause direct cytotoxic
      injury. Rarely, paraproteins that are resistant to proteolysis can crystallize
      within proximal tubules and cause acute tubular injury. In contrast, accumulation
      of crystallized paraproteins in other kidney cells, especially podocytes, is
      exceptional. Here, we report the finding of crystalline inclusions within
      podocytes and proximal tubules in a patient who presented with a combined
      nephrotic syndrome and Fanconi syndrome. Further workup revealed previously
      unsuspected multiple myeloma and elevated serum free light chains, highlighting
      the protean presentation of paraprotein-mediated injuries to the kidney. 

PMID- 24439930
TI  - Afatinib for lung cancer: let there be light?

PMID- 24439929
TI  - Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian
      patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX
      Lung 6): an open-label, randomised phase 3 trial.
AB  - BACKGROUND: Afatinib-an oral irreversible ErbB family blocker-improves
      progression-free survival compared with pemetrexed and cisplatin for first-line
      treatment of patients with EGFR mutation-positive advanced non-small-cell lung
      cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a
      chemotherapy regimen widely used in Asia-for first-line treatment of Asian
      patients with EGFR mutation-positive advanced NSCLC. METHODS: This open-label,
      randomised phase 3 trial was done at 36 centres in China, Thailand, and South
      Korea. After central testing for EGFR mutations, treatment-naive patients (stage
      IIIB or IV cancer [American Joint Committee on Cancer version 6], performance
      status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg
      per day) or intravenous gemcitabine 1000 mg/m(2) on day 1 and day 8 plus
      cisplatin 75 mg/m(2) on day 1 of a 3-week schedule for up to six cycles.
      Randomisation was done centrally with a random number-generating system and an
      interactive internet and voice-response system. Randomisation was stratified by
      EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three).
      Clinicians and patients were not masked to treatment assignment, but the
      independent central imaging review group were. Treatment continued until disease
      progression, intolerable toxic effects, or withdrawal of consent. The primary
      endpoint was progression-free survival assessed by independent central review
      (intention-to-treat population). This study is registered with
      ClinicalTrials.gov, NCT01121393. FINDINGS: 910 patients were screened and 364
      were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin).
      Median progression-free survival was significantly longer in the afatinib group
      (11.0 months, 95% CI 9.7-13.7) than in the gemcitabine and cisplatin group (5.6
      months, 5.1-6.7; hazard ratio 0.28, 95% CI 0.20-0.39; p<0.0001). The most common
      treatment-related grade 3 or 4 adverse events in the afatinib group were rash or
      acne (35 [14.6%] of 239 patients), diarrhoea (13 [5.4%]), and stomatitis or
      mucositis (13 [5.4%]), compared with neutropenia (30 [26.5%] of 113 patients),
      vomiting (22 [19.5%]), and leucopenia (17 [15.0%]) in the gemcitabine and
      cisplatin group. Treatment-related serious adverse events occurred in 15 (6.3%)
      patients in the afatinib group and nine (8.0%) patients in the gemcitabine and
      cisplatin group. INTERPRETATION: First-line afatinib significantly improves
      progression-free survival with a tolerable and manageable safety profile in Asian
      patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be
      considered as a first-line treatment option for this patient population. FUNDING:
      Boehringer Ingelheim.

PMID- 24439932
TI  - Community partnership to promote home fire safety in children with special needs.
AB  - BACKGROUND: Parents of children with special needs are vigilant as their child
      may have difficulty independently escaping a burning home. The purpose of this
      study was to evaluate if providing home fire safety information via a digital
      video disc (DVD) increases families' knowledge, behavior and ability regarding
      home fire safety. METHODS: A school based classroom intervention (using a home
      fire safety DVD) was provided to parents (n=40) of children with and without
      special needs to improve home fire safety knowledge, behavior and ability. In
      addition, parents seen at the Kentucky Commission for Children with Special
      Health Care Needs clinics (n=47) received the same intervention in cohorts of 1-2
      children. For both groups, knowledge, and behavior were measured before and after
      intervention. Repeated measures ANOVA were used to test for differences between
      groups and over time. Significance was set at p<0.05. RESULTS: No difference in
      scores between pre- and post-test scores existed between groups (with special
      needs vs. without special needs, or classroom vs. individualized instruction).
      However, some differences were noted for some individual survey questions during
      post-hoc comparisons. Having a smoke alarm in the home (90% vs. 95%, p=0.029) and
      having a smoke alarm outside of where everyone sleeps (75% vs. 95%, p=0.005)
      increased over time and was retained. Having a fire escape plan increased at post
      intervention (58% vs. 79%, p=0.033), but returned to pre levels at follow-up
      (58%). Perceived knowledge (7.7 vs. 9.3, p<0.001) and ability (8.7 vs. 9.1,
      p=0.069) increased over time. IMPLICATION FOR PRACTICE: Parents of children with
      special needs had a significant increase in knowledge and behavior over those
      parents of children without special needs. They also perceived having a high fire
      safety ability. Many of the post-test questions/behaviors (e.g., capable of
      exiting home during a fire, etc.) were reported at 100%. The intervention was
      well received, but may not necessarily be needed. Focus for home fire safety may
      need to look at younger children and smaller families. Parents of special needs
      children may have had frequent interaction with health care professionals.

PMID- 24439931
TI  - Cixutumumab for patients with recurrent or refractory advanced thymic epithelial
      tumours: a multicentre, open-label, phase 2 trial.
AB  - BACKGROUND: No standard treatment exists for refractory or relapsed advanced
      thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully
      human IgG1 monoclonal antibody targeting the insulin-like growth factor 1
      receptor in thymic epithelial tumours after failure of previous chemotherapy.
      METHODS: Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open
      label, phase 2 trial in patients aged 18 years or older with histologically
      confirmed recurrent or refractory thymic epithelial tumours. We enrolled
      individuals who had progressed after at least one previous regimen of platinum
      containing chemotherapy, had an Eastern Cooperative Oncology Group performance
      status of 0 or 1, and had measurable disease and adequate organ function.
      Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until
      disease progression or development of intolerable toxic effects. The primary
      endpoint was the frequency of response, analysed on an intention-to-treat basis.
      We also did pharmacodynamic studies. This trial is registered with
      ClinicalTrials.gov, number NCT00965250. FINDINGS: 49 patients were enrolled (37
      with thymomas and 12 with thymic carcinomas) who received a median of eight
      cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow
      up data were updated (Nov 30, 2012), median potential follow-up (from on-study
      date to most current follow-up date) was 24.0 months (IQR 17.3-36.9). In the
      thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial
      response, 28 had stable disease, and four had progressive disease. In the thymic
      carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five
      had stable disease, and seven had progressive disease. The most common grade 3-4
      adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase
      elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two
      each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune
      conditions during treatment (five were new-onset disorders), the most common of
      which was pure red-cell aplasia. Two (4%) patients died; one was attributed to
      disease progression and the other to disease-related complications (respiratory
      failure, myositis, and an acute coronary event), which could have been
      precipitated by treatment with cixutumumab. INTERPRETATION: Cixutumumab
      monotherapy is well-tolerated and active in relapsed thymoma. Development of
      autoimmunity during treatment needs further investigation. FUNDING: Division of
      Cancer Treatment and Diagnosis at the National Cancer Institute (National
      Institutes of Health), ImClone Systems.

PMID- 24439933
TI  - Epidemiology and referral patterns of burns admitted to the Burns Centre at
      Inkosi Albert Luthuli Central Hospital, Durban.
AB  - RATIONALE: The epidemiology, referral patterns and outcome of patients admitted
      to a tertiary burns unit in southern Africa were reviewed. MATERIALS AND METHODS:
      The charts of all patients with thermal injury presenting to the Burns Centre at
      Inkosi Albert Luthuli Central Hospital (IALCH) between 1 January 2008 and 31
      December 2010 were reviewed. Information collected included age, gender, past
      medical history, cause of burn, size of burn, presence of inhalation injury, time
      before admission, time to excision, length of hospital stay, complications and
      mortality. FINDINGS: Four hundred and sixty two patients were admitted, 296 (58%)
      children and 193 (42%) adults. The female-male ratio was 1:1.13. The mean total
      body surface area (TBSA) burned was 12% (interquartile range 8-25%) for children
      and 18% (interquartile range 10-35%) for adults. Common causes for the burns were
      in children: hot liquids (71%) and open flame (24%). Major causes in adults were:
      open fire (68%) and hot liquids (25%). Epilepsy was a contributing factor in
      12.7%. Inhalation injury was seen in 13.6% of adults and 14.3% of children with a
      flame burn. Forty-four percent of referrals from general surgical units were for
      burns <30% in adults, and 30% for burns <10% in children. More than one in four
      patients was referred between 1 and 6 weeks post-injury. Overall mortality was
      9.1% (5.7% in children and 15.1% in adults). Complications occurred in 21.6% of
      children and 36.7% in adults, the most common being lung complications such as
      ARDS and infection, severe sepsis, skin graft failure and contractures. The
      length of stay was 1 day/% TBSA burn for all burns in children and for burns
      between 10 and 49% in adults. CONCLUSIONS: The epidemiology and outcome of severe
      burns referred to the Burns Centre at IALCH is similar to those in other units in
      Africa. The management and referral of burns patients by other hospitals are
      inappropriate in a significant number of patients.

PMID- 24439934
TI  - Editors' note: Chloe E. Bird, PhD, named Editor-in-Chief of Women's Health
      Issues.

PMID- 24439935
TI  - Is depression associated with contraceptive motivations, intentions, and use
      among a sample of low-income Latinas?
AB  - BACKGROUND: Latinas in the United States experience high rates of unintended
      pregnancy and low rates of contraception use, yet reasons are not completely
      understood. Depression is common among pregnant and nonpregnant Latinas; its
      influence on contraceptive motivations, intentions, and use is understudied.
      OBJECTIVES: We sought to 1) describe Latinas' contraceptive motivations,
      intentions, and use; 2) use structural equation modeling to test associations
      between depression and contraceptive self-efficacy/motivations/intentions/use;
      and 3) determine whether associations differ by pregnancy status. METHODS: This
      cross-sectional study included Latinas ages 15 to 45 recruited from an urban
      Federally Qualified Health Center in Baltimore, Maryland. Structured surveys were
      used to collect data regarding depressive symptoms measured using the PHQ-9. All
      other constructs were measured with previously validated questions. Constructs
      included contraceptive self-efficacy, positive and negative contraceptive
      motivations (perceived advantages and disadvantages of using contraception),
      contraceptive intentions to begin or continue contraception use, and
      contraceptive methods currently used. RESULTS: Among pregnant Latinas, depression
      was associated with negative motivations (beta = 0.16; p < .05), negative
      motivations were associated with intentions (beta = -0.22; p < .01), and
      contraceptive self-efficacy was associated with intentions (beta = 0.43; p <
      .001). Among nonpregnant Latinas, contraceptive self-efficacy was associated with
      intentions (beta = 0.78; p < .001) and intentions were associated with use (beta
      = 0.40; p < .05). CONCLUSIONS: Among pregnant Latinas, negative motivations
      intervene in the association between depression and contraceptive intentions. For
      nonpregnant Latinas, intentions intervene in the association between self
      efficacy and contraceptive use. This study underscores the importance of
      depression screening during pregnancy and encourages practitioners to target
      contraceptive motivations to improve contraceptive use.

PMID- 24439936
TI  - Breastfeeding laws and breastfeeding practices by race and ethnicity.
AB  - OBJECTIVES: We sought to examine breastfeeding practices by race and ethnicity in
      areas with and without eight specific breastfeeding laws. METHODS: The 2003
      through 2010 National Health and Nutrition Examination Survey provides national
      breastfeeding practice information. We assessed eight breastfeeding laws before
      and after legislation was enacted and linked to population-based estimates of
      breastfeeding initiation and duration for children between birth and age one.
      FINDINGS: Relative to Whites, Mexican-American infants were 30% more likely to
      breastfeed for at least 6 months in areas with laws protecting break-time from
      work to pump, and 20% more likely to breastfeed for at least 6 months in areas
      with pumping law enforcement provisions. Unexpectedly, five laws with the
      intention of supporting breastfeeding duration were significantly less helpful
      for African-American women relative to White women. African-American women were
      nearly half as likely to breastfeed for at least 6 months, relative to Whites in
      areas with provisions to provide break-time from work (adjusted odds ratio [AOR],
      0.6; 95% confidence interval [CI], 0.5-0.8), private areas to pump at work (AOR,
      0.6; 95% CI, 0.4-0.8), exemption from jury duty (AOR, 0.6; 95% CI, 0.4-0.9),
      awareness education campaigns (AOR, 0.5; 95% CI, 0.3-0.8), and pumping law
      enforcement provisions (AOR, 0.6; 95% CI, 0.5-0.8). CONCLUSIONS: Breastfeeding
      laws influence African Americans and Mexican Americans differently than Whites.
      Examination of specific laws in conjunction with the interaction of known
      specific barriers for African-American mothers could help to achieve the Healthy
      People 2020 goals for breastfeeding.

PMID- 24439937
TI  - Implementing a prospective study of women seeking abortion in the United States:
      understanding and overcoming barriers to recruitment.
AB  - BACKGROUND: The Turnaway Study is designed to prospectively study the outcomes of
      women who sought-but did not all obtain-abortions. This design permits more
      accurate inferences about the health consequences of abortion for women, but
      requires the recruitment of a large number of women from remote health care
      facilities to a study a sensitive topic. This paper explores the Turnaway Study's
      recruitment process. METHODS: From 2008 to 2010, the staff at 30 abortion
      providing facilities recruited eligible female patients. Eight interventions were
      evaluated using multilevel logistic regression for their impact on eligible
      patients being approached, approached patients agreeing to go through informed
      consent by phone, and enrolled patients completing the baseline interview.
      FINDINGS: After site visits, patients had roughly twice the odds of being
      approached by facility staff and twice the odds of then agreeing to go through
      informed consent. When all recruitment steps were considered together, the net
      effect of site visits was to increase the odds that eligible patients
      participated by nearly a factor of six. After the introduction of a patient gift
      card incentive, patients had over three times the odds of agreeing to go through
      informed consent. With each passing month, however, staff demonstrated a 9%
      reduced odds of approaching eligible patients about the study. CONCLUSION:
      Prioritizing scientific rigor over the convenience of using existing datasets,
      the Turnaway Study confronted recruitment challenges common to medical practice
      based studies and unique to sensitive services. Visiting sites and communicating
      frequently with facility staff, as well as offering incentives to patients to
      hear more about the study before informed consent, may help to increase
      participation in prospective health studies and facilitate evaluation of
      sensitive women's health services.

PMID- 24439938
TI  - Prior family planning experiences of obese women seeking abortion care.
AB  - BACKGROUND: The prevalence of obesity among women of reproductive age calls for
      research focused on strategies that ensure obese women receive high-quality
      reproductive health care. This study adds to this literature on service delivery
      by exploring obese women's experiences receiving or avoiding family planning
      care. METHODS: We included 651 women seeking abortion care who completed iPad
      surveys about their previous family planning experiences. FINDINGS: One quarter
      were classified as obese, with almost 5% morbidly obese. Only 1% of obese women
      reported avoiding family planning care. More than 12% of morbidly obese women
      reported not having their family planning needs met (Pap smears, sexually
      transmitted infection testing, or ultrasonography). This is compared with only 2%
      among overweight and obese women and 0% among normal and underweight women.
      Almost 10% of obese and morbidly obese women reported that at least one of the
      previous family planning clinics they had visited was not prepared to provide
      care for heavier women and around 25% of obese women reported at least one item
      in the clinic (such as blood pressure cuffs and examination gowns) was not
      adequate for their size. RESULTS: Contrary to expectations, we did not find that
      obese women avoided family planning care. However, morbidly obese women reported
      not having all of their family planning needs met when they attended care. Family
      planning providers should ensure that their facilities have the capacity to meet
      the family planning needs of obese women and that they have adequate equipment to
      care for this population of women.

PMID- 24439939
TI  - The role of intimate partners in women's reasons for seeking abortion.
AB  - PURPOSE: The literature on partners and abortion focuses on intimate partner
      violence (IPV) and risk for abortion, and partners' control of women's abortion
      decisions. This paper examines how partners figure in women's abortion decisions,
      and identifies factors associated with identifying partner as a reason (PAR) for
      abortion. METHODS: Baseline data were used from the Turnaway Study, a
      longitudinal study among women (n = 954) seeking abortion at 30 U.S. facilities
      between 2008 and 2010. Mixed methods were used. Data were analyzed using thematic
      coding and logistic regression. FINDINGS: Nearly one third of women reported PAR
      for abortion. Three most common partner-related reasons were poor relationships,
      partners unable/unwilling to support a baby, and partner characteristics that
      made them undesirable to have a baby with. Eight percent who mentioned PAR
      identified having abusive partners as a reason for abortion. One woman in this
      subgroup reported being pressured by her partner to seek abortion, whereas others
      in this subgroup sought abortion to end abusive relationships or to avoid
      bringing children into abusive relationships. Factors associated with identifying
      PAR for seeking abortion included race, education, partner's pregnancy
      intentions, relationship with man involved in the pregnancy, and experience of
      IPV. CONCLUSION: Women make decisions to terminate pregnancies considering the
      quality of the relationship with and potential support they will receive from the
      man involved. Even women who report IPV, who may be vulnerable to coercion,
      report their motivation for the abortion is to end an abusive relationship,
      rather than coercion into abortion.

PMID- 24439940
TI  - Longitudinal patterns of breast cancer screening: mammography, clinical, and
      breast self-examinations in a rural and urban setting.
AB  - BACKGROUND: We identified breast screening patterns over time and patterns among
      women residing in rural and urban areas by sociodemographic factors. METHODS:
      This study employs a longitudinal design over 9 years from 2001 on 11,200 women
      aged 50 to 55 from the Australian Longitudinal Study on Women's Health. Area of
      residence was defined in accordance with the accessibility remoteness index of
      Australia Plus. Breast screening measures included mammography utilization,
      clinical breast examinations (CBE), and breast self-examinations (BSE). FINDINGS:
      Most women had a mammogram in the past 2 years in combination with CBE or BSE or
      both. Despite poorer access to mammography services, women residing in rural
      areas had similar mammography screening rates to their urban counterparts. Women
      residing in rural areas were less likely to have CBEs, but more likely to conduct
      BSEs. The breast screening behaviors were generally consistent over time.
      CONCLUSIONS: The poorer breast cancer survival among rural women is unlikely to
      be explained by differences in mammography service use. A substantial proportion
      of the population may be experiencing overscreening by conducting all three types
      of breast screening.

PMID- 24439941
TI  - Breast and cervical cancer screening disparities associated with disability
      severity.
AB  - BACKGROUND: Prior research has noted disparities between women with and without
      disabilities in receipt of timely screening for breast and cervical cancer. Some
      studies suggest greater disparities for women with more severe disabilities, but
      the research to date has yielded inconsistent findings. Our purpose was to
      further examine differences in receipt of breast and cervical cancer screening in
      relation to severity of disability. METHODS: We analyzed Medical Expenditure
      Panel Survey annual data files from 2002 to 2008. Logistic regression analyses
      examined whether Pap smears and mammograms had been received within the
      recommended timeframe according to U.S. Preventive Services Task Force
      Guidelines. We compared four groups of women aged 18 to 64 years, categorized by
      presence and complexity of disability: 1) No limitations, 2) basic action
      difficulties only, 3) complex activity limitations only, and 4) both basic and
      complex activity limitations. FINDINGS: Women both with and without disabilities
      fell short of Healthy People 2020 goals for breast and cervical cancer screening.
      Overall, women with disabilities were less likely to be up to date with both
      mammograms and Pap tests. The magnitude of disparities was greater for women with
      complex limitations. Disparities in Pap testing, but not mammography, remained
      significant when controlling for demographic, geographic, and socioeconomic
      factors. CONCLUSIONS: Women with more complex or severe disability were less
      likely to be up to date with breast and cervical cancer screenings. Targeted
      efforts are needed to reduce barriers to breast and cervical cancer screening for
      women with significant disabilities, especially those who also experience other
      socioecological disadvantages.

PMID- 24439943
TI  - A generation of childless women: lessons from the United States.
AB  - BACKGROUND: Childlessness is a major public health concern in the United States,
      particularly among educated adults. Among women who turned 45 in 2006, one fifth
      had no children. We examine the likelihood that a childless woman wants a baby
      sometime in the future and its determinants. METHODS: From 2006 to 2010, 5,410 in
      person interview surveys were conducted with childless women as part of the
      National Survey of Family Growth. Age-specific likelihoods of wanting a baby were
      compared with likelihoods of having a baby before age 45. Female respondents were
      1) born after 1960, 2) age 15 to 44, 3) childless (never given birth to a live
      infant), and 4) not pregnant at time of interview. FINDINGS: Most childless women
      at any age want a baby sometime in the future. By age 32, fewer than half the
      childless women who want a baby will have one. At age 39, the majority of
      childless women (73%) still want a baby someday, but only 7% will have one. By
      age 45, more than 1 in 10 women will be childless, but still want to have a baby.
      CONCLUSIONS: Although attitudes toward childlessness have become more positive
      over time, our findings suggest that the United States is experiencing a high
      prevalence of childless women who want a baby. Clinicians may consider counseling
      young women about age-related declines in fertility and the costs and success
      rates of assisted reproductive technologies often required for women with
      advanced maternal age to better inform their career, family, and lifestyle
      decisions.

PMID- 24439944
TI  - Will extending the Women's Health Initiative lead to better research and policy?

PMID- 24439942
TI  - Barriers reported among patients with breast and cervical abnormalities in the
      patient navigation research program: impact on timely care.
AB  - BACKGROUND: Patient navigation (PN) is a system-level strategy to decrease cancer
      mortality rates by reducing barriers to cancer care. Barriers to resolution among
      participants in the PN intervention arm with a breast or cervical abnormality in
      the Patient Navigation Research Program and navigators' actions to address those
      barriers were examined. METHODS: Data from seven institutions (2005-2010)
      included 1,995 breast and 1,194 cervical patients. A stratified Cox proportional
      hazards regression model was used to examine the effects of barriers on time to
      resolution of an abnormal screening test or clinical finding. FINDINGS: The range
      of unique barriers was 0 to 12 and 0 to 7 among participants with breast and
      cervical abnormalities, respectively. About two thirds of breast and one half of
      cervical participants had at least one barrier resulting in longer time to
      diagnostic resolution among breast (adjusted hazard ratio [HR], 0.744; p < .001)
      and cervical (adjusted HR, 0.792; p < .001) participants. Patient- and system
      level barriers were most common. Frequent navigator actions were making
      arrangements, scheduling appointments, referrals, and education. CONCLUSIONS:
      Having a barrier resulted in a delay in diagnostic resolution of an abnormal
      screening test or clinical finding. Health care systems can use these findings to
      improve existing PN programs or when developing new programs.

PMID- 24439945
TI  - Five-year trends in women veterans' use of VA maternity benefits, 2008-2012.
AB  - BACKGROUND: An increasing number of young women veterans are returning from war
      and military service and are seeking reproductive health care from the Veterans
      Health Administration (VHA). Many of these women seek maternity benefits from the
      VHA, and yet little is known regarding the number of women veterans utilizing VHA
      maternity benefits nor the characteristics of pregnant veterans using these
      benefits. In May 2010, VHA maternity benefits were expanded to include 7 days of
      infant care, which may serve to entice more women to use VHA maternity benefits.
      Understanding the changing trends in women veterans seeking maternity benefits
      will help the VHA to improve the quality of reproductive care over time.
      OBJECTIVE: The goal of this study was to examine the trends in delivery claims
      among women veterans receiving VHA maternity benefits over a 5-year period and
      the characteristics of pregnant veterans utilizing VHA benefits. DESIGN: We
      undertook a retrospective, national cohort study of pregnant veterans enrolled in
      VHA care with inpatient deliveries between fiscal years (FY) 2008 and 2012.
      PARTICIPANTS: We included pregnant veterans using VHA maternity benefits for
      delivery. MAIN MEASURES: Measures included annualized numbers and rates of
      inpatient deliveries and delivery-related costs, as well as cesarean section
      rates as a quality indicator. KEY RESULTS: During the 5-year study period, there
      was a significant increase in the number of deliveries to women veterans using
      VHA maternity benefits. The overall delivery rate increased by 44% over the study
      period from 12.4 to 17.8 deliveries per 1,000 women veterans. A majority of women
      using VHA maternity benefits were age 30 or older and had a service-connected
      disability. From FY 2008 to 2012, the VHA paid more than $46 million in delivery
      claims to community providers for deliveries to women veterans ($4,993/veteran).
      CONCLUSIONS: Over a 5-year period, the volume of women veterans using VHA
      maternity benefits increased by 44%. Given this sizeable increase, the VHA must
      increase its capacity to care for pregnant veterans and ensure care coordination
      systems are in place to address the needs of pregnant veterans with service
      connected disabilities.

PMID- 24439946
TI  - Stress, lifestyle, and quality of life in midlife and older Australian women:
      results from the Stress and the Health of Women Study.
AB  - BACKGROUND: Chronic psychological stress may pose a serious threat to health,
      although the mechanisms are not fully understood. This study examines the impact
      of stress on modifiable lifestyle factors, depressive symptoms, health-related
      quality of life (HRQOL) and chronic illness in older Australian women. METHODS:
      Cross-sectional data were collected from a random sample of 181 older adults aged
      60 to 70 years from rural and urban areas of South-East Queensland, Australia. We
      used structural equation modelling to examine associations between stress,
      modifiable lifestyle factors, HRQOL, and chronic illness. FINDINGS: Parameter
      estimates show that older women who reported life stressors where they felt
      helpless and feared for their life (high-magnitude stressors) also reported
      higher body mass index (p = .03) and more chronic illness (p < .01). In contrast,
      duration of exposure to life stressors was associated with higher depressive
      symptom scores (Center for Epidemiologic Studies Depression Scale; p = .02) and
      sleep disturbance scores (p < .01). CONCLUSIONS: Our findings support the link
      between traumatic personal histories (exposure to high-magnitude stressors) and
      unhealthy lifestyle factors. Findings highlight the need for more research on how
      stress reduction, a healthy lifestyle, and positive coping strategies can be used
      to reduce the effects of high-magnitude stress on HRQOL and chronic illness.

PMID- 24439947
TI  - Women and health reform: how national health care can enhance coverage,
      affordability, and access for women (examples from massachusetts).
AB  - BACKGROUND: Massachusetts women have the highest rates of health insurance
      coverage in the nation and women's access to care has improved across all
      demographic groups. However, important challenges persist. As national health
      reform implementation moves forward under the Affordable Care Act (ACA), states
      will likely encounter many of the same women's health challenges experienced in
      Massachusetts over the past 7 years. METHODS: A review of the literature and data
      analyses comparing health care services access, utilization, and cost, and health
      outcomes from Massachusetts pre- and post-2006 health care reform identified two
      key challenges in women's continuity of coverage and affordability. CONCLUSION:
      These areas are crucial for state and national policymakers to consider in
      improving women's health as they work to implement health care reform at the
      state and federal levels.

PMID- 24439948
TI  - Gender differences in cardiovascular risk factors in incident diabetes.
AB  - BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality
      for women and men with diabetes. Previous cross-sectional studies of prevalent
      diabetes have found that women are less likely to meet American Diabetes
      Association (ADA) and American Heart Association guidelines for control of
      cardiovascular risk factors (hemoglobin A1c, low-density lipoprotein [LDL]
      cholesterol, and blood pressure), but have not studied the critical period
      immediately after diagnosis. METHODS: To assess gender differences in
      cardiovascular risk factors at the time of diabetes diagnosis (baseline) and 1
      year later (follow-up), we conducted a retrospective cohort study of 6,547
      individuals with incident diabetes in an integrated care delivery system. We
      assessed mean cardiovascular risk factor values by gender and adjusted odds
      ratios of attaining ADA goals. FINDINGS: Compared with men, at baseline women had
      lower hemoglobin A1c (7.9% vs. 8.2%; p < .001), higher LDL cholesterol (118.9 vs.
      111.5 mg/dL; p < .001), higher systolic blood pressure (131.9 vs. 130.5 mmHg; p <
      .001), and lower diastolic blood pressure (79.1 vs. 79.7 mmHg; p = .006). At
      follow-up, the hemoglobin A1c gender gap had closed (6.9% vs. 6.9%; p = .39), and
      the gender gaps had decreased for blood pressure (129.8/77.0 vs. 128.9/77.6; p =
      .009) and LDL cholesterol (104.0 vs. 98.2 mg/dL; p < .001). These associations
      varied by age. Adjusted odds ratios showed similar relationships. CONCLUSIONS: In
      this cohort of individuals with incident diabetes, men and women had important
      differences in risk factor control at the time of diabetes diagnosis. These
      differences varied by age and decreased over time.

PMID- 24439949
TI  - Fracture risk perception study: patient self-perceptions of bone health often
      disagree with calculated fracture risk.
AB  - BACKGROUND: We sought to evaluate the concordance between self-assessed
      perceptions of fracture risk and actual risk calculated by World Health
      Organization's 10-year Fracture Risk Assessment Tool (FRAX). METHODS: We
      collected demographic data, lifestyle information, osteoporosis knowledge, bone
      density test results, and treatment history from patients aged 50 to 75 years.
      Subjects rated their perceptions of 10-year risk of sustaining fracture as low
      (0%-9%), intermediate (10%-19%), or high (>=20%). This rating was compared with
      risk calculated by FRAX. FINDINGS: Among 426 patients, the greatest agreement
      regarding fracture risk was noted for those in the low-risk FRAX group: 81%
      perceived themselves as having low risk. The most risk disagreement was in the
      high-risk FRAX group: Only 18% perceived their risk as high. Perceived risk was
      intermediate for 59% and low for 24%. Of patients at intermediate calculated risk
      by FRAX, 48% agreed with this with self-perceived risk. Overall, risk agreement
      was associated with bone density results, with higher T scores predictive of
      agreement. Underestimation was associated with being female and older. Patients
      with prescription treatment exposure frequently had risk disagreement and
      perceived their risk as lower than their calculated FRAX scores might indicate.
      Patients taking calcium and vitamin D similarly perceived lower risk than
      calculated by FRAX. CONCLUSIONS: Patients at intermediate and high calculated
      fracture risk frequently had self-perceptions of lower risk. Patients taking
      prescription osteoporosis medication and calcium and vitamin D treatment
      perceived less risk than calculated. Whether correcting misperceptions about
      personal susceptibility to fracture might result in behavioral changes will be
      determined.

PMID- 24439950
TI  - Alcohol use potentiates marijuana problem severity in young adult women.
AB  - BACKGROUND: Most young adult women who smoke marijuana also drink alcohol.
      Marijuana-related problems are associated with marijuana use frequency. We
      hypothesized that increased alcohol use frequency potentiates the association
      between frequency of marijuana use and marijuana-related problem severity.
      METHODS: We recruited women aged 18 to 24 who smoked marijuana at least monthly
      and were not treatment seeking. Marijuana and alcohol use were measured using the
      timeline follow-back method. Problems associated with marijuana use were assessed
      using the Marijuana Problems Scale. FINDINGS: Participants (n = 332) averaged
      20.5 +/- 1.8 years of age, were 66.7% non-Hispanic White, and reported using
      marijuana on 51.5 +/- 30.6 and alcohol on 18.9 +/- 16.8 of the 90 previous days.
      Controlling for education, ethnicity, years of marijuana use, and other drug use,
      frequency of marijuana use (b = .22; p < .01) and frequency of alcohol use (b =
      0.13; p < .05) had significant, positive effects on marijuana problem severity.
      In a separate multivariate model, the linear by linear interaction of marijuana
      by alcohol use frequency was significant (b = 0.18; p < .01), consistent with the
      hypothesis. CONCLUSIONS: Concurrent alcohol use impacts the experience of
      negative consequences from marijuana use in a community sample of young women.
      Discussions of marijuana use in young adults should consider the possible
      potentiating effects of alcohol use.

PMID- 24439951
TI  - Preparedness planning for emergencies among postpartum women in arkansas during
      2009.
AB  - PURPOSE: Having an emergency plan may reduce negative effects of disaster on the
      health of postpartum women and their infants. However, little is known about the
      prevalence of emergency plans among postpartum women. In 2009, Arkansas added a
      question to the Pregnancy Risk Assessment Monitoring System surveillance system
      about whether women who gave birth that year had an emergency plan. In this
      study, we first describe the sociodemographic characteristics, disaster
      experience, and region of residence of postpartum women in Arkansas who indicated
      that they had an emergency plan for their families in 2009, and second, examine
      associations between sociodemographic characteristics and disaster experience and
      the presence of an emergency plan. METHODS: Multivariable logistic regression (n
      = 1,173) was conducted to examine associations between maternal race/ethnicity,
      sociodemographic characteristics, region of residence, disaster experience, and
      having a disaster plan. We adjusted for maternal education, federal poverty
      level, and family size in our final model. FINDINGS: Forty-eight percent (n =
      559) of women reported having an emergency plan. Hispanic women were less likely
      to report having a plan compared with non-Hispanic White women (n = 102 [10%];
      adjusted prevalence ratio [aPR], 0.6; 95% confidence interval [CI], 0.4-0.9).
      Families with five or more members were more likely to have a plan compared with
      smaller families (n = 123 [11%]; aPR, 1.3; 95% CI, 1.1-1.6). CONCLUSIONS:
      Policymakers and public health practitioners can use these results to promote
      emergency planning among postpartum women in Arkansas, with special outreach to
      postpartum women who are Hispanic or have smaller families.

PMID- 24439952
TI  - Selected preconception health indicators and birth weight disparities in a
      national study.
AB  - BACKGROUND: This analysis explored the effect of timing, sequencing, and change
      in preconception health across adolescence and young adulthood on racial/ethnic
      disparities in birth weight in a diverse national cohort of young adult women.
      METHODS: Data came from Waves I (1994-1995), III (2001-2002), and IV (2007-2008)
      of the National Longitudinal Study of Adolescent Health. Eligibility was
      restricted to all singleton live births to female non-Hispanic White, non
      Hispanic Black, Mexican-origin Latina, or Asian/Pacific Islander participants (n
      = 3,014) occurring between the Wave III (ages 18-26 years) and IV (ages 24-32
      years) interviews. Birth weight was categorized into low (<2,500 g), normal
      (2,500-4,000 g), and macrosomic (>4,000 g). Preconception health indicators were
      cigarette smoking, heavy alcohol consumption, overweight or obesity, and
      inadequate physical activity, measured in adolescence (Wave I, ages 11-19 years)
      and early adulthood (Wave III) and combined into four-category variables to
      capture the timing and sequencing of exposure. FINDINGS: Measures of
      preconception health did not explain the Black-White disparity in low birth
      weight, which increased after adjustment for confounders (odds ratio [OR], 2.17;
      95% confidence interval [CI], 1.33-3.53) and effect modification by
      overweight/obesity (OR, 3.58; 95% CI, 1.65-7.78). A positive association between
      adult-onset overweight/obesity and macrosomia was modified by race (OR, 3.83; 95%
      CI, 1.02-14.36 for Black women). CONCLUSIONS: This longitudinal analysis provides
      new evidence on preconception health and racial/ethnic disparities in birth
      weight. Specifically, it indicates that interventions focused on prevention of
      overweight/obesity and maintenance of healthy weight during the transition to
      adulthood, especially among Black females, may be warranted.

PMID- 24439954
TI  - Grid pattern delivered to the cornea during femtosecond laser-assisted cataract
      surgery.
AB  - A 63-year-old patient had cataract surgery in the left eye performed using the
      femtosecond laser. The laser successfully created the capsulotomy, but as the
      femtosecond lens fragmentation was being performed, the patient suddenly moved
      and the eye disengaged from the patient interface. As this happened, the surgeon
      stopped the treatment, but inspection of the cornea revealed a partial lens
      fragmentation grid pattern in the temporal cornea. This inadvertent occurrence
      did not affect the final surgical result. FINANCIAL DISCLOSURE: Dr. Yoo is a
      consultant to Abbott Medical Optics, Inc. No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24439953
TI  - Exercise during pregnancy and risk of late preterm birth, cesarean delivery, and
      hospitalizations.
AB  - BACKGROUND: Federal physical activity guidelines recommend at least 150 minutes
      of moderate-intensity exercise per week during pregnancy. We studied whether
      regular exercise during pregnancy is associated with preterm birth, cesarean
      delivery, and hospitalization during pregnancy. METHODS: Self-reported weekly
      exercise was ascertained in 3,006 women during the third trimester of pregnancy.
      Using multivariable logistic regression, we report the relationship between
      regular exercise (>=150 min/wk) and late preterm birth, cesarean delivery, and
      hospitalization during pregnancy, controlling for age, race, marital status,
      education, poverty status, prepregnancy body mass index weight category,
      gestational weight gain, and prepregnancy diabetes or hypertension. RESULTS:
      Nearly one third of women reported meeting current federal physical activity
      recommendations during pregnancy. Five percent had late preterm birth, 29% had
      cesarean deliveries, and 20% reported hospitalization during pregnancy. In
      multivariable analysis, regular exercise during pregnancy was not associated with
      late preterm birth or hospitalization during pregnancy. Physical activity of 150
      or more minutes per week was associated with reduced odds of cesarean delivery
      compared with less than 60 minutes per week, but the finding was not significant
      (adjusted odds ratio, 0.86; 95% confidence interval, 0.69-1.07). CONCLUSION: In
      the First Baby Study, physical activity was not associated with late preterm
      birth or hospitalizations, and may be associated with decreased odds of cesarean
      delivery.

PMID- 24439956
TI  - Single-nucleotide polymorphism rs6690993 in FGGY is not associated with
      amyotrophic lateral sclerosisin a large Chinese cohort.
AB  - The single-nucleotide polymorphisms (SNPs) rs6700125 and rs6690993 in FGGY
      (FLJ10986) were recently reported to be a susceptibility factor for sporadic
      amyotrophic lateral sclerosis (SALS) in Caucasian populations in genome-wide
      association studies. However, no such association was observed in other
      independent genome-wide association studies or replication studies in a European
      cohort or 2 small sample sizes of Chinese patients. We performed a large case
      control study in a cohort consisting of 963 SALS cases and 1039 control subjects
      to examine the association between the 2 reported SNPs in FGGY and amyotrophic
      lateral sclerosisin Chinese patients. Our results did not find the SNP rs6690993
      in FGGY is associated with Chinese SALS and cannot confirm that this FGGY SNP
      modulates the risk for SALS in the Chinese population. 

PMID- 24439957
TI  - Age-associated dysregulation of microglial activation is coupled with enhanced
      blood-brain barrier permeability and pathology in APP/PS1 mice.
AB  - Aging adversely affects inflammatory processes in the brain, which has important
      implications in the context of disease progression. It has been proposed that
      microglia become dysfunctional with age and may lose their neuroprotective
      properties leading to chronic neurodegeneration. Here, we sought to characterize
      inflammatory changes in a mouse model of Alzheimer's disease and to delineate
      differences between normal aging and those associated with disease pathology. A
      proinflammatory profile, characterized by the upregulation of markers of
      classical activation, was evident in APPswe/PS1dE9 mice, associated with
      increased interferon-gamma (IFNgamma) concentration and dysregulation of
      mechanisms designed to limit the proinflammatory response. The data indicate that
      microglia are not less active with age but alter their phenotype; indeed, changes
      observed in the deactivation state appear to relate to aging rather than disease
      pathology. We hypothesize that disruption of the blood-brain barrier, in tandem
      with an enhanced chemokine profile, permits the infiltration of immune cells
      serving to reinforce classical activation of microglia through their enhanced
      responsiveness to IFNgamma. 

PMID- 24439958
TI  - Testing the calcium hypothesis of aging in the rat hippocampus in vivo using
      manganese-enhanced MRI.
AB  - In this study, we noninvasively tested the hypothesis that Mn(2+)-enhanced
      magnetic resonance imaging (MEMRI) is sensitive to age-related changes in Ca(2+)
      influx occurring in the hippocampal region CA1. Uptake of Mn(2+), an MRI contrast
      agent and Ca(2+) surrogate with low cellular efflux rates (days to weeks), was
      measured in longitudinal MEMRI studies involving 2 separate groups of male Long
      Evans rats: one group was studied at 2.5 and 7 months of age, whereas the other
      was studied at 7 and 19 months of age. Separate or combined analysis revealed
      that the extent of Mn(2+) accumulation in CA1 significantly increased with age (p
      < 0.05). These results provide first-time in vivo confirmation of the calcium
      hypothesis of aging and justify future longitudinal studies combining MEMRI with
      behavioral testing to investigate mechanisms of age-related cognitive decline.

PMID- 24439955
TI  - Susceptibility loci for pigmentation and melanoma in relation to Parkinson's
      disease.
AB  - Growing evidence suggests that Parkinson's disease (PD) patients have a lower
      risk for most types of cancer except for melanoma, which has a modest positive
      association with PD. Pigmentation genes have been hypothesized to contribute to
      this association. We therefore examined whether genetic susceptibility loci for
      pigmentation or melanoma was associated with PD risk in 2 large independent
      datasets. In the Parkinson's Genes and Environment (PAGE) study, we examined 11
      single-nucleotide polymorphisms (SNPs) identified from previous genome-wide
      association studies (GWAS) of pigmentation or melanoma in relation to PD among
      808 PD cases and 1623 controls; furthermore, we also examined the colors of hair,
      eye, or skin and melanoma in relation to PD. In the International Parkinson's
      Disease Genomic Consortium (IPDGC), we examined a broader selection of 360
      pigmentation or melanoma GWAS SNPs in relation to PD among 5,333 PD cases and
      12,019 controls. All participants were non-Hispanic Whites. As expected, in the
      PAGE study, most SNPs were associated with 1 or more pigmentation phenotypes.
      However, neither these SNPs nor pigmentation phenotypes were associated with PD
      risk after Bonferroni correction with the exception of rs4911414 at the ASIP gene
      (p = .001). A total of 18 PD cases (2.2%) and 26 controls (1.6%) had a diagnosis
      of melanoma with an odds ratio of 1.3 (95% confidence interval: 0.7-2.4). In the
      IPDGC analysis, none of the 360 SNPs, including rs4911414, were associated with
      PD risk after adjusting for multiple comparisons. In conclusion, we did not find
      significant associations between GWAS SNPs of pigmentation or melanoma and the
      risk for PD.

PMID- 24439960
TI  - The effects of individualized theta burst stimulation on the excitability of the
      human motor system.
AB  - BACKGROUND: Theta burst stimulation (TBS) is a pattern of repetitive transcranial
      magnetic stimulation that has been demonstrated to facilitate or suppress human
      corticospinal excitability when applied intermittently (iTBS) or continuously
      (cTBS), respectively. While the fundamental pattern of TBS, consisting of bursts
      of 50 Hz stimulation repeated at a 5 Hz theta frequency, induces synaptic
      plasticity in animals and in vitro preparations, the relationship between TBS and
      underlying cortical firing patterns in the human cortex has not been elucidated.
      OBJECTIVE: To compare the effects of 5 Hz iTBS and cTBS with individualized TBS
      paradigms on corticospinal excitability and intracortical inhibitory circuits.
      METHODS: Participants received standard and individualized iTBS (iTBS 5; iTBS I)
      and cTBS (cTBS 5; cTBS I), and sham TBS, in a randomised design. For
      individualized paradigms, the 5 Hz theta component of the TBS pattern was
      replaced by the dominant cortical frequency (4-16 Hz; upper frequency restricted
      by technical limitations) for each individual. RESULTS: We report that iTBS 5 and
      iTBS I both significantly facilitated motor evoked potential (MEP) amplitude to a
      similar extent. Unexpectedly, cTBS 5 and cTBS I failed to suppress MEP amplitude.
      None of the active TBS protocols had any significant effects on intracortical
      circuits when compared with sham TBS. CONCLUSION: In summary, iTBS facilitated
      MEP amplitude, an effect that was not improved by individualizing the theta
      component of the TBS pattern, while cTBS, a reportedly inhibitory paradigm,
      produced no change, or facilitation of MEP amplitude in our hands.

PMID- 24439959
TI  - Testing a neurobiological model of depersonalization disorder using repetitive
      transcranial magnetic stimulation.
AB  - BACKGROUND: Depersonalization disorder (DPD) includes changes in subjective
      experiencing of self, encompassing emotional numbing. Functional magnetic
      resonance imaging (fMRI) has pointed to ventrolateral prefrontal cortex (VLPFC)
      inhibition of insula as a neurocognitive correlate of the disorder. OBJECTIVE: We
      hypothesized that inhibition to right VLPFC using repetitive transcranial
      magnetic stimulation (rTMS) would lead to increased arousal and reduced symptoms.
      METHODS: Patients with medication-resistant DSM-IV DPD (N = 17) and controls (N =
      20) were randomized to receive one session of right-sided rTMS to VLPFC or
      temporo-parietal junction (TPJ). 1 Hz rTMS was guided using neuronavigation and
      delivered for 15 min. Co-primary outcomes were: (a) maximum skin conductance
      capacity, and (b) reduction in depersonalization symptoms (Cambridge
      Depersonalisation Scale (CDS) [state version]). Secondary outcomes included
      spontaneous fluctuations (SFs) and event-related skin conductance responses.
      RESULTS: In patients with DPD, rTMS to VLPFC led to increased electrodermal
      capacity, namely maximum skin conductance deflections. Patients but not controls
      also showed increased SFs post rTMS. Patients who had either VLPFC or TPJ rTMS
      showed a similar significant reduction in symptoms. Event-related electrodermal
      activity did not change. CONCLUSIONS: A single session of right-sided rTMS to
      VLPFC (but not TPJ) significantly increased physiological arousal capacity
      supporting our model regarding the relevance of increased VLPFC activity to
      emotional numbing in DPD. rTMS to both sites led to reduced depersonalization
      scores but since this was independent of physiological arousal, this may be a non
      specific effect. TMS is a potential therapeutic option for DPD; modulation of
      VLPFC, if replicated, is a plausible mechanism.

PMID- 24439961
TI  - Blaschkitis under certolizumab for rheumatoid arthritis.

PMID- 24439962
TI  - Reply to the comment "Effect of Infliximab on Male Fertility" by Younis et al.

PMID- 24439963
TI  - Biomechanical loading of the sacrum in adolescent idiopathic scoliosis.
AB  - BACKGROUND: The pelvis maintains an important role in transferring loads from the
      upper body to the lower extremities and hence contributes to the standing
      postural balance. Even though changes in spino-pelvic relative alignment are
      involved in the pathophysiology of scoliosis, the mechanism through which the
      transferred load between the spine and pelvis is related to the spinal deformity
      is not well understood. METHODS: A personalized finite element model of the spine
      and pelvis was constructed for 11 right main thoracic and 23 left
      thoracolumbar/lumbar adolescent idiopathic scoliosis and 12 asymptomatic
      controls. The compressive stress distribution on the sacrum endplate was
      computed. The position of the stress distribution barycenter on the sacrum
      superior endplate in reference to the central hip vertical axis was projected on
      the transverse plane and compared between scoliotic subgroups and controls.
      FINDINGS: The medio-lateral position of the stress distribution barycenter on the
      sacrum superior endplate was significantly different between the scoliotic
      subgroups and controls (p<0.05). The stress distribution barycenter on the sacrum
      superior endplate was located at the right side of the central hip vertical axis
      in 82% of the right main thoracic patients and to the left side of the central
      hip vertical axis in 91% of the left thoracolumbar/lumbar patients.
      INTERPRETATION: Analysis of the transferred load to the sacrum provided insight
      into the biomechanical spino-pelvic interaction in 3D, showing that a
      thoracolumbar/lumbar scoliotic curve has an increased influence on sacral loads
      when compared to a main thoracic scoliotic curve.

PMID- 24439964
TI  - Body mass index, dose to organs at risk during vaginal brachytherapy, and the
      role of three-dimensional CT-based treatment planning.
AB  - PURPOSE: To assess the effect of body mass index (BMI) on dose to organs at risk
      (OARs) during high-dose-rate vaginal brachytherapy and evaluate the role of three
      dimensional dose evaluation during treatment planning. METHODS AND MATERIALS:
      Three-dimensional dosimetric data for rectum, bladder, sigmoid colon, and small
      bowel for 125 high-dose-rate vaginal brachytherapy fractions were analyzed. Dose
      volume histograms were generated for D0.1 cc and D2 cc of each OAR. Contributing
      factors including the use of urinary catheter and cylinder size were also
      recorded. As different dose fractionations were used, the OAR doses were
      tabulated as a percent dose prescribed to 0.5cm. All patients were treated to 4cm
      of the vaginal length. RESULTS: Median BMI in this cohort was 31.7kg/m(2). The
      BMI values had a weak inverse correlation with D0.1 cc to sigmoid colon (rs=
      0.18, p=0.047) and D0.1 cc to bladder (rs=-0.19, p=0.038). There was a strong
      inverse correlation of D2 cc and increasing BMI (rs=-0.64, p=0.003). The median
      D2 cc was 25.1% for BMI higher than 31 and 61.9% for BMI of 31 or lower. For D0.1
      cc, there was also a strong inverse correlation with increasing BMI (rs=-0.57,
      p<0.001). Median D1 cc was 33.5% for BMI >31 and 84.4% for BMI <= 31. On
      multivariate analysis higher BMI remained a significant predictor of lower small
      bowel D2 cc (p<0.001) and D0.1 cc (p<0.001). CONCLUSIONS: Women with a lower BMI
      receive higher doses to the bladder and small bowel compared with those with a
      higher BMI. Three-dimensional dose evaluation should be considered in patients
      with low BMI, particularly when combined with external beam radiation.

PMID- 24439966
TI  - Accuracy of the composite somatic cell count to detect intra-mammary infection in
      dairy cows using latent class analysis.
AB  - The somatic cell count (SCC) is considered an important indicator of intra
      mammary infection (IMI). The purpose of this study was to determine the accuracy
      of both SCC and culture to detect IMI and their conditional dependence by means
      of latent class methods. This study involved 175 dairy cows from 2 herds with
      different udder infection prevalences. Quarter and composite milk samples were
      collected for SCC and bacteriological culture. Latent-class models using Bayesian
      methods were used to estimate test sensitivity (Se) and specificity (Sp) and
      population prevalence. The models ran involved only major mastitis pathogens and
      composite SCC (CSCC). Five thresholds between 100,000 and 300,000 cells/mL were
      evaluated and the receiver operating characteristics (ROC) curve analysis was
      performed. Fifty-five percent of the cows had CSCC >=200,000 cells/mL and 95.4%
      of the cows had at least one infected quarter either with minor or major
      pathogens. Considering a threshold of 150,000 cells/mL, the estimated Se and Sp
      for the CSCC were, 0.80 (95% CrI 0.71-0.88) and 0.57 (95% CrI 0.44-0.71),
      respectively. The estimated culture Se and Sp were 0.83 (95% CrI 0.73-0.93) and
      0.89 (95% CrI 0.74-0.98), respectively. There was no evidence of dependence
      between CSCC and culture. The area under curve for CSCC was 0.72. To the best of
      our knowledge, this is the first report of the CSCC accuracy to detect IMI for
      major pathogens considering the effect of culture misclassification. The
      estimates provided here could help to examine the performance of sampling schemes
      based on CSCC to manage udder health.

PMID- 24439967
TI  - Biomarkers for the prognosis of pulmonary arterial hypertension: Holy Grail or
      flying circus?
AB  - Despite recent and major progresses in the field of pulmonary vascular diseases
      pulmonary arterial hypertension (PAH) outcome still needs improvement. In
      parallel, several changes are observed in a disease that is no longer described
      as typically affecting young women. This is outlined in the most recent reports
      from PAH registries, where increasing age at the time of diagnosis is constantly
      described. Regardless the cause of this changing face, the quest for the perfect
      prognostic factor in PAH is ongoing. Among the numerous variables of interest,
      biomarkers are particularly attractive, as they do not require expertise or
      invasive procedure. This is the case for brain natriuretic peptide (BNP) and the
      inactive N-terminal cleavage product of its pro-hormone (NT-proBNP), which have
      proven to be reliable. This might also be the case for endothelin-1 (ET-1), a
      potent vasoactive peptide involved in the endothelin pathway and its biologically
      stable surrogate, carboxy-terminal pro-endothelin-1 (CT-proET1) that could
      independently predict 1-year event-free survival in PAH. Of course, further
      research is warranted to confirm these results. Yet, even if there are probably
      few chances, if any, to discover the "Holy Grail", researcher's efforts must
      continue. The combination of pertinent parameters in composite scores is indeed
      promising and emphasized in the most recent PAH guidelines. Clinicians would
      probably need to use a subtle combination of several biomarkers and clinical,
      functional, hemodynamic and right ventricular parameter criteria to drive the
      most ambitious treatment goals in a complex and life threatening disease. 

PMID- 24439965
TI  - Trafficking of endosomal Toll-like receptors.
AB  - Over the past decade we have learned much about nucleic acid recognition by the
      innate immune system and in particular by Toll-like receptors (TLRs). These
      receptors localize to endosomal compartments where they are poised to recognize
      microbial nucleic acids. Multiple regulatory mechanisms function to limit
      responses to self DNA or RNA, and breakdowns in these mechanisms can contribute
      to autoimmune or inflammatory disorders. In this review we discuss our current
      understanding of the cell biology of TLRs involved in nucleic acid recognition
      and how localization and trafficking of these receptors regulates their function.

PMID- 24439968
TI  - Extracorporeal carbon dioxide removal through ventilation of acidified dialysate:
      an experimental study.
AB  - BACKGROUND: Extracorporeal (EC) carbon dioxide (CO(2)) removal (ECCO(2)R) may be
      a powerful alternative to ventilation, possibly avoiding the need for mechanical
      ventilation and endotracheal intubation. We previously reported how an infusion
      of lactic acid before a membrane lung (ML) effectively enhances ECCO(2)R. We
      evaluated an innovative ECCO(2)R technique based on ventilation of acidified
      dialysate. METHODS: Four swine were sedated, mechanically ventilated, and
      connected to a venovenous dialysis circuit (blood flow, 250 ml/min). The
      dialysate was recirculated in a closed loop circuit including a ML (gas flow, 10
      liters/min) and then returned to the dialyzer. In each animal, 4 different
      dialysis flows (DF) of 200, 400, 600, and 800 ml/min were evaluated with and
      without lactic acid infusion (2.5 mEq/min); the sequence was completed 3 times.
      At the end of each step, we measured the volume of CO(2)R by the ML (V(co2)ML)
      and collected blood and dialysate samples for gas analyses. RESULTS: Acid
      infusion substantially increased V(co2)ML, from 33 +/- 6 ml/min to 86 +/- 7
      ml/min. Different DFs had little effect on V(co2)ML, which was only slightly
      reduced at DF 200 ml/min. The partial pressure of CO(2) of blood passing through
      the dialysis filter changed from 60.9 +/- 3.6 to 37.1 +/- 4.8 mm Hg without
      acidification and to 32.5 +/- 5.3 mm Hg with acidification, corresponding to a pH
      increase of 0.18 +/- 0.03 and 0.03 +/- 0.04 units, respectively. CONCLUSIONS:
      Ventilation of acidified dialysate efficiently increased ECCO(2)R of an amount
      corresponding to 35% to 45% of the total CO(2) production of an adult man from a
      blood flow as low as 250 ml/min.

PMID- 24439969
TI  - ACEMg supplementation ameliorates progressive Connexin 26 hearing loss in a
      child.
AB  - Mutations in the gene encoding Connexin 26 are the most common cause of genetic
      hearing loss. The hearing loss is typically stable but may be progressive. The
      reason for progression is unknown. Antioxidants have been associated with
      attenuation of hearing loss from other insults. One antioxidant regimen consists
      of beta-carotene (metabolized to vitamin A), vitamin C, vitamin E, and magnesium
      (ACEMg). We present a child with Connexin 26 related hearing loss who experienced
      progressive hearing loss over 7 years of observation. He was given ACEMg daily
      for 3 years, during which time his progressive hearing loss was ameliorated. 

PMID- 24439970
TI  - Associative conditioning can increase liking for and consumption of brussels
      sprouts in children aged 3 to 5 years.
AB  - Pairing foods with liked flavors repeatedly can increase preferences for those
      foods. We compared the effectiveness of associative conditioning (pairing
      vegetables with sweetened and unsweetened cream cheese) and exposure (presenting
      vegetables alone) in increasing liking and consumption of bitter and nonbitter
      vegetables. Twenty-nine children (aged 3 to 5 years) participated in the study.
      One group of children received brussels sprouts (bitter) with sweetened cream
      cheese and cauliflower (nonbitter) with unsweetened cream cheese and a second
      group received the reverse pairing. A third group received brussels sprouts and
      cauliflower with no cream cheese. Pairing brussels sprouts with cream cheese
      increased liking and consumption more than exposure, whereas cauliflower was
      liked by all groups regardless of presence of cream cheese. Associative
      conditioning was more effective than exposure in increasing liking for a novel,
      bitter vegetable-brussels sprouts-whereas exposure alone was effective for a
      nonbitter, more familiar vegetable-cauliflower. 

PMID- 24439971
TI  - Forme fruste cases of Takotsubo syndrome: a hypothesis.

PMID- 24439972
TI  - TRIple pill vs Usual care Management for Patients with mild-to-moderate
      Hypertension (TRIUMPH): Study protocol.
AB  - BACKGROUND: Hypertension management strategies have traditionally focused on
      "tailored therapy" and "stepped-care" approaches. These tend to be costly and
      time consuming and often fail to achieve adequate blood pressure (BP) control.
      The TRIUMPH study aims to investigate the effectiveness, cost-effectiveness, and
      acceptability of early use of a 3-in-1 BP-lowering pill ("Triple Pill") compared
      with usual care for the management of hypertension. METHODS: The prospective,
      open, randomized controlled clinical trial (n = 700) will compare Triple Pill
      based strategy to usual care among individuals with persistent mild-to-moderate
      hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg, or systolic
      BP >130 mm Hg and/or diastolic BP >80 mm Hg in patients with diabetes or chronic
      kidney disease) on no or minimal drug therapy. The study will be conducted within
      approximately 20 hospital-based clinics in India. Participants will be randomized
      to the Triple Pill (initially strength 1-telmisartan 20 mg, amlodipine 2.5 mg,
      hydrochlorothiazide 6.25 mg, with the option of subsequent titration to strength
      2-telmisartan 40 mg, amlodipine 5 mg, hydrochlorothiazide 12.5 mg) or continued
      usual care. Participants will be followed up for 6 months. The primary outcome is
      the proportion of participants achieving target BP at the end follow-up.
      CONCLUSION: This study will determine whether early use of a low-dose triple
      combination therapy has the potential to address some of the challenges in
      hypertension control through earlier achievement of BP control, better adherence,
      and fewer adverse effects, in the context of less intensive clinical follow-up.

PMID- 24439973
TI  - Amsterdam Investigator-initiateD Absorb strategy all-comers trial (AIDA trial): a
      clinical evaluation comparing the efficacy and performance of ABSORB everolimus
      eluting bioresorbable vascular scaffold strategy vs the XIENCE family (XIENCE
      PRIME or XIENCE Xpedition) everolimus-eluting coronary stent strategy in the
      treatment of coronary lesions in consecutive all-comers: rationale and study
      design.
AB  - BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold
      (AbsorbBVS) is a completely resorbable device engineered to overcome the
      limitations of permanent metallic stents, providing temporary scaffolding and
      antiproliferative drug delivery for the treatment of obstructive coronary artery
      disease. METHODS: The objective of the AIDA trial is to evaluate the efficacy and
      performance in an contemporary all-comer population of the AbsorbBVS strategy vs
      the XIENCE family everolimus-eluting metallic coronary stent system in the
      treatment of coronary lesions. The AIDA trial is a prospective, randomized (1:1),
      active-control, single-blinded, all-comer, noninferiority trial. A total of 2,690
      subjects will be enrolled with broad inclusion and limited exclusion criteria
      according to the "Instructions for Use" of the AbsorbBVS strategy. The study
      population includes both simple and complex lesions, in patients with stable and
      acute coronary syndrome. The follow-up continues for 5years. The primary end
      point of the trial is target vessel failure, defined as the composite of cardiac
      death, myocardial infarction, and target vessel revascularization, at 2years.
      This study is registered on ClinicalTrials.gov with number NCT01858077.
      CONCLUSION: The AIDA trial will provide the first randomized direct comparison
      between the everolimus-eluting bioresorbable vascular scaffold and the everolimus
      eluting metallic stent in contemporary percutaneous coronary intervention
      practice.

PMID- 24439975
TI  - Comparison of automated measurements of electrocardiographic intervals and
      durations by computer-based algorithms of digital electrocardiographs.
AB  - BACKGROUND AND PURPOSE: Automated measurements of electrocardiographic (ECG)
      intervals are widely used by clinicians for individual patient diagnosis and by
      investigators in population studies. We examined whether clinically significant
      systematic differences exist in ECG intervals measured by current generation
      digital electrocardiographs from different manufacturers and whether differences,
      if present, are dependent on the degree of abnormality of the selected ECGs.
      METHODS: Measurements of RR interval, PR interval, QRS duration, and QT interval
      were made blindly by 4 major manufacturers of digital electrocardiographs used in
      the United States from 600 XML files of ECG tracings stored in the US FDA ECG
      warehouse and released for the purpose of this study by the Cardiac Safety
      Research Consortium. Included were 3 groups based on expected QT interval and
      degree of repolarization abnormality, comprising 200 ECGs each from (1) placebo
      or baseline study period in normal subjects during thorough QT studies, (2) peak
      moxifloxacin effect in otherwise normal subjects during thorough QT studies, and
      (3) patients with genotyped variants of congenital long QT syndrome (LQTS).
      RESULTS: Differences of means between manufacturers were generally small in the
      normal and moxifloxacin subjects, but in the LQTS patients, differences of means
      ranged from 2.0 to 14.0 ms for QRS duration and from 0.8 to 18.1 ms for the QT
      interval. Mean absolute differences between algorithms were similar for QRS
      duration and QT intervals in the normal and in the moxifloxacin subjects (mean
      <=6 ms) but were significantly larger in patients with LQTS. CONCLUSIONS: Small
      but statistically significant group differences in mean interval and duration
      measurements and means of individual absolute differences exist among automated
      algorithms of widely used, current generation digital electrocardiographs.
      Measurement differences, including QRS duration and the QT interval, are greatest
      for the most abnormal ECGs.

PMID- 24439974
TI  - Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial
      STiffness and central hemodynamics: rationale and design of the EARNEST study.
AB  - BACKGROUND: There is strong evidence of an association between chronic kidney
      disease (CKD) and cardiovascular disease. To date, however, proof that a
      reduction in glomerular filtration rate (GFR) is a causative factor in
      cardiovascular disease is lacking. Kidney donors comprise a highly screened
      population without risk factors such as diabetes and inflammation, which
      invariably confound the association between CKD and cardiovascular disease. There
      is strong evidence that increased arterial stiffness and left ventricular
      hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the
      adverse cardiovascular effects of CKD. The expanding practice of live kidney
      donation provides a unique opportunity to study the cardiovascular effects of an
      isolated reduction in GFR in a prospective fashion. At the same time, the
      proposed study will address ongoing safety concerns that persist because most
      longitudinal outcome studies have been undertaken at single centers and compared
      donor cohorts with an inappropriately selected control group. HYPOTHESES: The
      reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent
      increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in
      peripheral and central blood pressure. METHODS: This is a prospective,
      multicenter, longitudinal, parallel group study of 440 living kidney donors and
      440 healthy controls. All controls will be eligible for living kidney donation
      using current UK transplant criteria. Investigations will be performed at
      baseline and repeated at 12 months in the first instance. These include
      measurement of arterial stiffness using applanation tonometry to determine pulse
      wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory
      blood pressure monitoring, and a series of biomarkers for cardiovascular and bone
      mineral disease. CONCLUSIONS: These data will prove valuable by characterizing
      the direction of causality between cardiovascular and renal disease. This should
      help inform whether targeting reduced GFR alongside more traditional
      cardiovascular risk factors is warranted. In addition, this study will contribute
      important safety data on living kidney donors by providing a longitudinal
      assessment of well-validated surrogate markers of cardiovascular disease, namely,
      blood pressure and arterial stiffness. If any adverse effects are detected, these
      may be potentially reversed with the early introduction of targeted therapy. This
      should ensure that kidney donors do not come to long-term harm and thereby
      preserve the ongoing expansion of the living donor transplant program
      (NCT01769924).

PMID- 24439976
TI  - Association of all-cause and cardiovascular mortality with prehypertension: a
      meta-analysis.
AB  - BACKGROUND: Studies of prehypertension and mortality are controversial after
      adjusting for other cardiovascular risk factors. This meta-analysis sought to
      evaluate the association of prehypertension with all-cause and cardiovascular
      disease (CVD) mortality. METHODS: The PubMed, EMBASE, Cochrane Library databases,
      and conference proceedings were searched for studies with data on prehypertension
      and mortality. The relative risks (RRs) of all-cause, CVD, coronary heart disease
      (CHD), and stroke mortality were calculated and presented with 95% CIs. Subgroup
      analyses were conducted according to blood pressure, age, gender, ethnicity,
      follow-up duration, participant number, and study characteristics. RESULTS: Data
      from 1,129,098 participants were derived from 20 prospective cohort studies.
      Prehypertension significantly increased the risk of CVD, CHD, and stroke
      mortality (RR 1.28, 95% CI 1.16-1.40; RR 1.12, 95% CI 1.02-1.23; and RR 1.41, 95%
      CI 1.28-1.56, respectively), but did not increase the risk of all-cause mortality
      after multivariate adjustment (RR 1.03, 95% CI 0.97-1.10). The difference between
      CHD mortality and stroke mortality was significant (P < .001). Subgroup analyses
      showed that CVD mortality was significantly increased in high-range
      prehypertension (RR 1.28, 95% CI 1.16-1.41) but not in low-range prehypertension
      (RR 1.08, 95% CI 0.98-1.18). CONCLUSION: Prehypertension is associated with CVD
      mortality, especially with stroke mortality, but not with all-cause mortality.
      The risk for CVD mortality is largely driven by high-range prehypertension.

PMID- 24439977
TI  - Arm exercise as an alternative to pharmacologic stress testing: arm exercise
      stress testing and outcome.
AB  - BACKGROUND: Treadmill exercise variables are powerful predictors of all-cause
      mortality but are unobtainable in at least 50% of patients because of
      disabilities precluding lower extremity exercise. Arm exercise stress testing is
      a potentially cost-effective alternative, but no long-term outcome data are
      available. METHODS: We performed arm ergometer stress tests on 446 veterans aged
      64.0 (11.1) years (mean [SD]) between 1997 and 2002 and investigated whether arm
      exercise capacity in resting metabolic equivalents, heart rate recovery (in beats
      per minute), delta (peak resting) heart rate (in beats per minute), and other
      exercise variables predict long-term all-cause mortality, myocardial infarction
      (MI), or coronary revascularization. RESULTS: During follow-up of 12.0 (1.3)
      years, 255 patients died (57.2%), 70 had MI (15.7%), and 118 underwent coronary
      revascularization (26.4%). After adjustment for significant demographic and
      clinical variables, death was predicted by arm metabolic equivalents (hazard
      ratio/SD 0.59, 95% CI 0.46-0.75, P < .001), heart rate recovery (hazard ratio/SD
      0.64, 95% CI 0.49-0.83, P < .001), and delta heart rate (hazard ratio/SD 0.75,
      95% CI 0.63-0.91, P < .001). No exercise variables prognosticated MI, but
      coronary revascularization was predicted by stress-induced ST-segment deviations
      (hazard ratio 2.64, 95% CI 1.16-4.33, P < .001), limiting angina (hazard ratio
      4.70, 95% CI 1.81-12.22, P < .001), and an abnormal perfusion imaging result
      (hazard ratio 2.0, 95% CI 1.14-3.51, P < .02). CONCLUSIONS: Arm exercise
      capacity, heart rate recovery, and delta heart rate predict 12-year all-cause
      mortality and arm exercise-induced ST changes, limiting angina, and an abnormal
      nuclear imaging result portend coronary revascularization in lower extremity
      disabled veterans.

PMID- 24439978
TI  - Erectile dysfunction in the cardiology practice-a patients' perspective.
AB  - BACKGROUND: Erectile dysfunction (ED) is an independent risk factor for
      cardiovascular events sharing mutual risk factors with coronary artery disease.
      Several guidelines for the management of ED in cardiovascular disease have been
      proposed, recommending cardiologists to routinely inquire about erectile
      function. However, males' specific needs and wishes regarding sexual health care
      in cardiology are unknown. We sought to identify male patients' view concerning
      possible improvements in sexual health care and preferred forms of sexual
      counseling in the cardiology practice. METHODS: This is a cross-sectional
      multicentered survey study among randomly selected males visiting a cardiologist.
      RESULTS: Of 388 respondents, 296 questionnaires were eligible for analysis. Mean
      age of respondents was 62.9 years. Overall, 56% (n = 165) had ED, with up to 86%
      in patients with heart failure. Mean bother experienced due to ED was 5.93 (+/
      2.57) on a 0 to 10 scale. Most respondents indicated to feel comfortable
      discussing sexual health with the cardiologists (88%). Of men with ED (n = 165),
      46% would like to have a conversation with the cardiologist about possibilities
      to improve sexual function, 55% would be helped if questions could be asked
      during consultation with a specialized nurse, and 58% would appreciate written
      information. Of all respondents (n = 296), 28% ever tried a phosphodiesterase
      inhibitor; 4% received the prescription of the cardiologists. CONCLUSIONS:
      Erectile dysfunction is highly prevalent in patients with a variety of
      cardiovascular diagnosis and care for sexual function is mandatory. Patients
      indicated that above consultation with the cardiologist, both consultation with a
      specialized nurse and written information would be helpful.

PMID- 24439979
TI  - Growth differentiation factor 15 and cardiovascular events in patients with
      stable ischemic heart disease (The Heart and Soul Study).
AB  - BACKGROUND: Growth differentiation factor 15 (GDF-15) is a relatively new
      biomarker that predicts mortality in patients with chronic stable angina or acute
      coronary syndrome. However, the association of GDF-15 with cardiovascular (CV)
      events and the mechanisms of this association are not well understood. METHODS:
      We measured plasma GDF-15 and cardiac disease severity in 984 patients with
      stable ischemic heart disease who were recruited for the Heart and Soul Study
      between September 2000 and December 2002. Subsequent CV events (myocardial
      infarction, stroke, and CV death), hospitalization for heart failure, and all
      cause mortality were determined by chart review during an average of 8.9-year
      follow-up. RESULTS: Each doubling in GDF-15 was associated with a 2.5-fold
      increased rate of CV events (hazard ratio [HR] 2.53, 95% CI 2.13-3.01, P < .001).
      This association persisted after extensive adjustment for covariates including
      comorbid conditions, measures of cardiac disease severity, cardiac function,
      inflammatory markers, and adipokines (HR 1.44, 95% CI 1.11-1.87, P < .01).
      Participants who had GDF-15 levels in the highest tertile had higher mortality
      compared with those in the lowest tertile (HR 2.73, 95% CI 1.80-4.15, P <= .001
      adjusted for all covariates). Addition of GDF-15 to existing risk factors
      resulted in a 50% change in net reclassification of patients' risk for mortality.
      CONCLUSIONS: Higher levels of GDF-15 are associated with major CV events in
      patients with stable ischemic heart disease. This suggests that GDF-15 is
      capturing an element of risk not explained by other known risk factors.

PMID- 24439980
TI  - The effects of exercise on cardiovascular biomarkers in patients with chronic
      heart failure.
AB  - BACKGROUND: Exercise training is recommended for chronic heart failure (HF)
      patients to improve functional status and reduce risk of adverse outcomes.
      Elevated plasma levels of amino-terminal pro-brain natriuretic peptide (NT
      proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T
      (cTnT) are associated with increased risk of adverse outcomes in this patient
      population. Whether exercise training leads to improvements in biomarkers and how
      such improvements relate to clinical outcomes are unclear. METHODS AND RESULTS:
      Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were
      assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION
      study, a randomized clinical trial of exercise training versus usual care in
      chronic HF patients with reduced left ventricular ejection fraction (<35%).
      Linear and logistic regressions were used to assess 3-month biomarker levels as a
      function of baseline value, treatment assignment (exercise training vs usual
      care), and volume of exercise. Linear regression and Cox proportional hazard
      modeling were used to evaluate the relations between changes in biomarker levels
      and clinical outcomes of interest that included change in peak oxygen consumption
      (peak VO2), hospitalizations, and mortality. Exercise training was not associated
      with significant changes in levels of NT-proBNP (P = .10), hs-CRP (P = .80), or
      detectable cTnT levels (P = .83) at 3 months. Controlling for baseline biomarker
      levels or volume of exercise did not alter these findings. Decreases in plasma
      concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with
      increases in peak VO2 (P < .001) at 3 months and decreased risk of
      hospitalizations or mortality (P <= .04), even after adjustment for a
      comprehensive set of known predictors. CONCLUSIONS: Exercise training did not
      lead to meaningful changes in biomarkers of myocardial stress, inflammation, or
      necrosis in patients with chronic HF. Only improvements in NT-proBNP translated
      to reductions in peak VO2 and reduced risk of clinical events.

PMID- 24439981
TI  - Absolute survival after cardiac resynchronization therapy according to baseline
      QRS duration: a multinational 10-year experience: data from the Multicenter
      International CRT Study.
AB  - BACKGROUND: In the major trials of cardiac resynchronization therapy (CRT), the
      survival benefit of the therapy, relative to control subjects, increases with QRS
      duration. In the non-CRT heart failure population, however, a wide QRS duration
      is associated with a shorter survival. Relative survival benefit from a therapy,
      however, is not synonymous with a longer absolute survival. We sought to
      determine whether baseline QRS duration relates to the absolute survival after
      CRT. METHODS AND RESULTS: In this prospective, longitudinal, observational study,
      3,319 consecutive patients undergoing CRT (QRS 120-149 ms 26%, QRS 150-199 ms
      58%, and QRS >=200 ms 16%) were assessed in relation to mortality over 10 years.
      Overall mortality rates (per 100 patient-years) were 9.2%, 9.3%, and 13.3% in the
      3 groups, respectively (all P < .001). Cardiac mortality rates were 6.2, 6.0, and
      9.9 per 100 patient-years, respectively (all P < .001). Compared with the QRS 120
      149 ms group, cardiac mortality was highest in the QRS >=200 ms group (hazard
      ratio [HR] 1.72 [95% CI 1.35-2.19], P < .001), independent of age, gender, New
      York Heart Association class, presence of atrial fibrillation, heart failure
      etiology, and left ventricular ejection fraction. Median survival after CRT was
      longest in patients with a width of QRS 120-149 ms and shortest in patients with
      a QRS >=200 ms (P < .001). In multivariable analyses, a QRS >=200 ms emerged as a
      powerful independent predictor of both overall (HR 1.44 [95% CI 1.07-1.94], P =
      .017) and cardiac mortality (HR 1.59 [95% CI 1.14-2.24], P = .007). CONCLUSIONS:
      At long-term follow-up, absolute overall and cardiac survival after CRT is
      similar in patients with a preimplant QRS duration of 120 to 149 ms and 150 to
      199 ms but markedly shorter in patients with a QRS >=200 ms.

PMID- 24439982
TI  - EPITOME-2: An open-label study assessing the transition to a new formulation of
      intravenous epoprostenol in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Continuous infusion of epoprostenol is the treatment of choice in
      patients with pulmonary arterial hypertension in functional classes III to IV.
      However, this treatment's limitations include instability at room temperature. A
      new epoprostenol formulation offers improved storage conditions and patient
      convenience. METHODS: The EPITOME-2 trial was an open-label, prospective,
      multicenter, single-arm, phase IIIb study. Patients with pulmonary arterial
      hypertension on long-term, stable epoprostenol therapy were transitioned from
      epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline,
      Durham, NC) to epoprostenol with arginine and sucrose excipients (Veletri;
      Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Patients were followed up
      for 3 months, and dose adjustments were recorded. Efficacy measures included the
      6-minute walk distance, hemodynamics assessed by right heart catheterization, and
      New York Heart Association functional class. Safety and tolerability of the
      transition were also evaluated. Quality of life was assessed using the Treatment
      Satisfaction Questionnaire for Medication. RESULTS: Forty-two patients enrolled
      in the study, and 1 patient withdrew consent before treatment; thus, 41 patients
      received treatment and completed the study. Six patients required dose
      adjustments. There were no clinically relevant changes from baseline to month 3
      in any of the efficacy end points. Adverse events were those previously described
      with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for
      Medication scores showed an improvement from baseline to month 3 in the domain of
      treatment convenience. CONCLUSIONS: Transition from epoprostenol with glycine and
      mannitol excipients to epoprostenol with arginine and sucrose excipients did not
      affect treatment efficacy, raised no new safety or tolerability concerns, and
      provided patients with an increased sense of treatment convenience.

PMID- 24439983
TI  - Two formulations of epoprostenol sodium in the treatment of pulmonary arterial
      hypertension: EPITOME-1 (epoprostenol for injection in pulmonary arterial
      hypertension), a phase IV, open-label, randomized study.
AB  - BACKGROUND: Epoprostenol sodium with arginine-mannitol excipients (epoprostenol
      AM; Veletri [Actelion Pharmaceuticals Ltd, Allschwil, Switzerland]) and
      epoprostenol sodium with glycine-mannitol excipients (epoprostenol GM; Flolan
      [GlaxoSmithKline, Triangle Park, NC]) are intravenous treatments for pulmonary
      arterial hypertension (PAH). Epoprostenol AM contains different inactive
      excipients, resulting in greater stability at room temperature compared with
      epoprostenol GM. METHODS: In this prospective, multicenter, open-label,
      randomized, phase IV exploratory study, epoprostenol-naive patients in need of
      injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM
      or epoprostenol GM. The study period was 28 days, followed by a 30-day safety
      follow-up. Study aims were to descriptively compare the safety, tolerability,
      drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol
      GM in PAH. Statistical analysis was descriptive only because of the exploratory
      nature of the study. RESULTS: Thirty patients with PAH (18-70 years, 24 women, 20
      idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n
      = 10). Most frequently reported adverse events included jaw pain, headache,
      nausea, and flushing. Two deaths occurred during the study period, and 1 death
      occurred during the 30-day safety follow-up period, all in patients receiving
      epoprostenol AM. All deaths were classified by the treating physician as
      unrelated to epoprostenol AM. The median (range) change from baseline to day 28
      in 6-minute walk distance was 36 m (-127 to 210 m) and 49 m (-44 to 110 m) for
      the epoprostenol AM and epoprostenol GM groups, respectively. CONCLUSIONS: In
      this randomized clinical study of epoprostenol AM in PAH, use of this novel
      preparation with greater room temperature stability was well tolerated.

PMID- 24439984
TI  - Short-term hemodynamic effect of angiotensin-converting enzyme inhibition in
      patients with severe aortic stenosis: a placebo-controlled, randomized study.
AB  - BACKGROUND: In patients with severe aortic stenosis (AS), treatment with
      angiotensin-converting enzyme inhibitors has previously been considered
      contraindicated. However, there is a lack of clinical evidence to confirm these
      potential hemodynamic risks and benefits. METHODS: Forty-four patients with
      severe AS (aortic valve area <1 cm(2)) were randomized to treatment with
      trandolapril 22 mg daily/placebo (1:1). Right heart catheterization and
      echocardiography were performed at rest and during exercise at baseline and on
      day 3. Follow-up was performed before valve replacement or after a maximum of 8
      weeks, when exercise echocardiography was repeated. RESULTS: Compared with
      placebo, systolic blood pressure and systemic arterial compliance significantly
      changed at day 3 (-14 +/- 11 vs -5 +/- 13 mm Hg, P = .02, and 0.08 +/- 0.16 vs 
      0.05 +/- 0.86 mL/m(2) per mm Hg, P = .03, respectively). Changes in left
      ventricular end systolic volume (LVESV) was nonsignificant (-8 +/- 9 vs -3 +/- 11
      mL, P = .17). At a median of 49 days of follow-up, changes in LVESV and N
      terminal pro-brain natriuretic peptide were even lower revealing significant
      differences between the groups (-7.8 +/- 2.6 vs -0.5 +/- 2.5 mL, P = .04, and -19
      +/- 7 vs 0.8 +/- 6 pmol/L, P = .04, respectively). No episodes of symptomatic
      hypotension were noted, and other hemodynamic parameters remained unchanged.
      CONCLUSION: Angiotensin-converting enzyme inhibition in severe AS caused a
      decrease in LVESV and N-terminal pro-brain natriuretic peptide with other
      hemodynamic parameters preserved both at rest and during exercise implying
      hemodynamic improvement with left ventricular unloading.

PMID- 24439985
TI  - Balloon aortic valvuloplasty in the era of transcatheter aortic valve
      replacement: acute and long-term outcomes.
AB  - BACKGROUND: The use of balloon aortic valvuloplasty (BAV) has resurged since the
      development of transcatheter aortic valve replacement (TAVR). The aim of our
      study was to determine the procedural and long-term outcomes of patients treated
      by BAV in the early TAVR era. METHODS: From 2005 to 2008, 323 consecutive
      patients presenting with severe aortic stenosis were treated by BAV in our
      institution. RESULTS: Mean age and logistic EuroSCORE were 80.5 +/- 9.9 years and
      28.7% +/- 12.5%, respectively. The effective orifice area increased from 0.68 +/-
      0.25 to 1.12 +/- 0.39 cm(2) (P < .001) after BAV. Inhospital major complications
      occurred in 22 patients (6.8%), with a mortality rate of 2.5%. Eighty-five
      patients (26.3%) were bridged to surgical aortic valve replacement (SAVR, 9.6%)
      or TAVR (16.7%). Twenty-eight patients (8.7%) had at least 1 repeat BAV. Two
      hundred ten patients (65%) received only medical therapy post-BAV. Mean duration
      of follow-up was 20.7 +/- 20.0 months. Kaplan-Meier analysis demonstrated that
      survival after single BAV was poor. Patients treated by BAV followed by SAVR or
      TAVR had the highest long-term survival rate (P < .001). Multivariable analysis
      revealed that logistic EuroSCORE, severe aortic regurgitation and stroke
      complications post-BAV, and medical therapy post-BAV were independent predictors
      of mortality. CONCLUSIONS: The results of our study suggest that BAV is an
      acceptable bridge to SAVR or TAVR in a very high-risk population not immediately
      suitable for definitive therapy. Balloon aortic valvuloplasty remains only a
      brief temporizing procedure with a poor long-term outcome without subsequent
      definitive therapy.

PMID- 24439986
TI  - Multicenter randomized trial of 3-month cilostazol use in addition to dual
      antiplatelet therapy after biolimus-eluting stent implantation for long or
      multivessel coronary artery disease.
AB  - BACKGROUND: There are conflicting data on the use of cilostazol as triple
      antiplatelet therapy (TAPT) for improving clinical outcomes after drug-eluting
      stent implantation. We aimed to evaluate whether 3-month use of cilostazol in
      addition to dual antiplatelet therapy (DAPT) improved clinical outcomes in
      patients with long or multivessel coronary artery disease (CAD) after biolimus
      eluting stent (BES) implantation. METHODS: Patients (n = 630) who had been
      successfully treated with BES implantation for lesions with >=28 mm in stent
      length or >=2 stents for different coronary arteries were enrolled in this
      prospective randomized multicenter trial. All patients were randomly assigned to
      receive either DAPT (aspirin and clopidogrel for 12 months, n = 314) or TAPT
      (DAPT plus 3-month cilostazol use, n = 316). The primary end point was a device
      oriented composite consisting of cardiac death, myocardial infarction (not
      clearly attributable to a nontarget vessel), and ischemia-driven target lesion
      revascularization at 1-year follow-up. RESULTS: A total of 314 patients in DAPT
      and 308 patients in TAPT were analyzed. Multivessel CAD was present in 65.7% of
      patients. Stents >=28 mm in length were implanted in 58.1% of lesions. There were
      no significant differences in baseline and angiographic characteristics between
      the 2 groups. The primary end point was similar between the 2 groups (2.3% in
      DAPT vs 1.9% in TAPT, log-rank P = .799). CONCLUSIONS: In patients treated with
      BES implantation for long or multivessel CAD, 3 months of cilostazol use in
      addition to DAPT did not improve clinical outcome at 1-year follow-up.

PMID- 24439987
TI  - A survey of the 3-decade outcome for patients with giant aneurysms caused by
      Kawasaki disease.
AB  - BACKGROUND: Our purpose was to determine the outcome in patients with a more-than
      20-year history of giant coronary aneurysms (GAs) caused by Kawasaki disease
      (KD). METHODS: Between 2010 and 2011, the incidence and outcome of cardiac events
      (CEs) in patients with GA was surveyed by questionnaire by the Kinki area Society
      of KD research. Death, acute myocardial infarction (AMI), coronary artery bypass
      grafting (CABG), percutaneous coronary catheter intervention, syncope, and
      ventricular tachycardia were considered as CEs. Survival rate and CE-free rate
      were analyzed by the Kaplan-Meier method. RESULTS: We enrolled 245 patients (187
      were male, 58 were female), 141 with bilateral GA and 104 with unilateral GA. The
      interval between the onset of acute KD to the time of survey ranged from 0.2 to
      51 years, and the median was 20 years. Death, AMI, and CABG occurred in 15 (6%),
      57 (23%), and 90 patients (37%), respectively. The CE-free rate and the survival
      rate at 30 years after KD were 36% (95% CI 28-45) and 90% (95% CI 84-94),
      respectively. The 30-year survival rate for bilateral GA was 87% (95% CI 78-93),
      and for unilateral GA, it was 96% (95% CI 85-96; hazard ratio 4.60, 95% CI 1.27
      29.4, P = .027). The 30-year survival rate in patients with AMI was 49% (95% CI
      27-71), and the 25-year survival rate in patients undergoing CABG was 92% (95% CI
      81-98). CONCLUSIONS: The outcome differed significantly between bilateral GA and
      unilateral GA. The results focus attention on the need to preserve myocardial
      perfusion, especially in high-risk patients with bilateral GA. An understanding
      of the optimal CABG would be useful in bilateral GA.

PMID- 24439988
TI  - Patterns and prognosis of all components of the J-wave pattern in multiethnic
      athletes and ambulatory patients.
AB  - BACKGROUND: Despite recent concern about the significance of the J-wave pattern
      (also often referred to as early repolarization) and the importance of screening
      in athletes, there are limited rigorous prognostic data characterizing the 3
      components of the J-wave pattern (ST elevation, J waves, and QRS slurs). We aim
      to assess the prevalence, patterns, and prognosis of the J-wave pattern among
      both stable clinical and athlete populations. METHODS: We retrospectively studied
      4,041 electrocardiograms from a multiethnic clinical population from 1997 to 1999
      at the Veterans Affairs Palo Alto Health Care System. We also examined
      preparticipation electrocardiograms of 1,114 Stanford University varsity athletes
      from 2007 to 2008. Strictly defined criteria for components of the J-wave pattern
      were examined. In clinical subjects, prognosis was assessed using the end point
      of cardiovascular death after 7 years of follow-up. RESULTS: Components of the J
      wave pattern were most prevalent in males; African Americans; and, particularly,
      athletes, with the greatest variations demonstrated in the lateral leads. ST
      elevation was the most common. Inferior J waves and slurs, previously linked to
      cardiovascular risk, were observed in 9.6% of clinical subjects and 12.3% of
      athletes. J waves, slurs, or ST elevation was not associated with time to
      cardiovascular death in clinical subjects, and ST-segment slope abnormalities
      were not prevalent enough in conjunction with them to reach significance.
      CONCLUSIONS: J waves, slurs, or ST elevation was not associated with increased
      hazard of cardiovascular death in our large multiethnic, ambulatory population.
      Even subsets of J-wave patterns, recently proposed to pose a risk of arrhythmic
      death, occurred at such a high prevalence as to negate their utility in
      screening.

PMID- 24439989
TI  - Influence of heart failure symptoms and ejection fraction on short- and long-term
      outcomes for older patients with non-ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Symptomatic heart failure (HF) and reduced ejection fraction (REF)
      are both associated with mortality, but the long-term outcomes associated with
      the development of HF in older non-ST-segment elevation myocardial infarction
      (NSTEMI) patients with preserved systolic function and REF are uncertain.
      METHODS: We analyzed a total of 26,291 NSTEMI patients >=65 years discharged
      alive in the CRUSADE Registry who had linked Medicare data. We evaluated 30-day
      and 1-year risks of mortality and HF readmission in 4 cohorts of patients
      stratified by symptomatic HF and ejection fraction: (1) no HF-PEF, (2) no HF-REF,
      (3) HF-PEF, and (4) HF-REF. RESULTS: A total of 14,280 NSTEMI patients (54.3%)
      had no HF-PEF, 3,345 (12.7%) had no HF-REF, 4,913 (18.7%) had HF-PEF, and 3,753
      (14.3%) had HF-REF. Compared with no HF-PEF patients, the 30-day mortality risk
      was higher among patients with no HF-REF (4.9% vs 1.7%, adjusted hazard ratio
      2.11, 95% CI 1.69-2.63), HF-PEF (5.9% vs 1.7%, adjusted hazard ratio 1.99, 95% CI
      1.64-2.41), and highest among those with HF-REF (9.3% vs 1.7%, adjusted hazard
      ratio 2.70, 95% CI 2.23-3.26). Similar relationships were noted in the adjusted 1
      year mortality and the risks of 30-day and 1-year HF readmission. CONCLUSIONS:
      Symptomatic HF and REF during the index NSTEMI hospitalization are both
      associated with an increased risk of short- and long-term mortality as well as HF
      readmission with an apparent additive prognostic impact of both factors.

PMID- 24439990
TI  - Genetic diversity of the KCNE1 gene and susceptibility to postoperative atrial
      fibrillation.
AB  - BACKGROUND: The human KCNE1 protein forms the beta-subunit of the IKs potassium
      channel and is important in the regulation of the atrial action potential
      duration. The purpose of this study was to investigate the association between
      the nonsynonymous 112G>A mutation of the KCNE1 gene and postcardiac surgery
      atrial fibrillation (AF). METHODS AND RESULTS: A cohort of patients scheduled for
      cardiac surgery was prospectively recruited. The genotype of 112G>A polymorphism
      was determined using polymerase chain reaction/restriction fragment analysis and
      confirmed with direct sequencing of the polymerase chain reaction product. In
      total, 509 patients were recruited in the study, of whom 203 (39.9%) had at least
      1 qualifying episode of postoperative AF. An increased frequency of the G allele
      was observed in the postoperative AF group compared with the group without
      postoperative AF (0.628 vs 0.552, respectively, P = .016). The individual's
      relative risk of postoperative AF increased as the number of G alleles increased
      from 1.36 (95% CI 0.89-2.08) for G allele heterozygotes to 1.62 (95% CI 1.08
      2.43) for G allele homozygotes (P = .04 for trend). The multivariate analysis
      revealed the abnormal ejection fraction (odds ratio [OR] 1.585, 95% CI 1.076
      2.331, P = .020), age (OR 1.043, 95% CI 1.022-1.064, P < .001), type of surgery
      (aortic valve replacement) (OR 1.869, 95% CI 1.094-3.194, P = .022), and the
      112G>A genotype (OR 1.401 [in additive model], 95% CI 1.052-1.865, P = .021) to
      be independent predictors of postoperative AF. CONCLUSION: This study confirmed
      the association of the 112G>A polymorphism and postoperative AF in a cohort of
      patients undergoing cardiac surgery.

PMID- 24439991
TI  - Use of preoperative cardiac troponin T to identify patients at risk for acute
      myocardial infarction and long-term mortality after major noncardiac surgery.

PMID- 24439992
TI  - Letter in response to "Use of preoperative cardiac troponin T to identify
      patients at risk for acute myocardial infraction and long-term mortality after
      major noncardiac surgery".

PMID- 24439993
TI  - Calibration and validation of a phenomenological influent pollutant disturbance
      scenario generator using full-scale data.
AB  - The objective of this paper is to demonstrate the full-scale feasibility of the
      phenomenological dynamic influent pollutant disturbance scenario generator
      (DIPDSG) that was originally used to create the influent data of the
      International Water Association (IWA) Benchmark Simulation Model No. 2 (BSM2). In
      this study, the influent characteristics of two large Scandinavian treatment
      facilities are studied for a period of two years. A step-wise procedure based on
      adjusting the most sensitive parameters at different time scales is followed to
      calibrate/validate the DIPDSG model blocks for: 1) flow rate; 2) pollutants
      (carbon, nitrogen); 3) temperature; and, 4) transport. Simulation results show
      that the model successfully describes daily/weekly and seasonal variations and
      the effect of rainfall and snow melting on the influent flow rate, pollutant
      concentrations and temperature profiles. Furthermore, additional phenomena such
      as size and accumulation/flush of particulates of/in the upstream catchment and
      sewer system are incorporated in the simulated time series. Finally, this study
      is complemented with: 1) the generation of additional future scenarios showing
      the effects of different rainfall patterns (climate change) or influent
      biodegradability (process uncertainty) on the generated time series; 2) a
      demonstration of how to reduce the cost/workload of measuring campaigns by
      filling the gaps due to missing data in the influent profiles; and, 3) a critical
      discussion of the presented results balancing model structure/calibration
      procedure complexity and prediction capabilities. 

PMID- 24439994
TI  - Comparative study of biphasic calcium phosphate with beta-tricalcium phosphate in
      rat cranial defects--A molecular-biological and histological study.
AB  - The aim of this study was to evaluate the in vivo biocompatibility of a biphasic
      calcium phosphate (BCP) bone graft substitute consisting of 60% hydroxyapatite
      and 40% beta-tricalcium phosphate (beta-TCP) in comparison to a pure beta-TCP of
      identical shape and porosity. The materials were evaluated using an established
      rat cranial defect model in 24 animals. One bone defect with a diameter of 5mm
      was created per animal. The defects were filled with either BCP or beta-TCP and
      left to heal for 4 weeks. Twelve samples (6 per material) were processed for
      histological evaluation and immunohistochemistry. The remaining 12 samples were
      processed for mRNA expression analysis. No signs of inflammation or adverse
      material reactions were detected. New bone formation in the former defect site
      did not differ between the two groups (BCP: 49.2%; beta-TCP: 52.4%). Osteoblast
      like and TRAP-positive osteoclast-like cells were found at the surface of the
      bone graft substitute granules. The beta-TCP group showed significantly higher
      mRNA levels for the bone resorption marker Acp5 and osteogenic differentiation
      marker Runx2. The expression of IGF1, IGF2, VEGF, Phex, Alpl, Col1, Col2, Bglap
      and MMP8 did not differ between the groups. The in vivo biocompatibility of BCP
      is to a large part identical to those of TCP. Within the limitation of the animal
      model, the implantation study shows that BCP can be used as bone graft
      substitute, due to the fact that the material integrates into tissue, remains
      stable in the implantation bed and serves as an osteoconductive scaffold. 

PMID- 24439995
TI  - Longitudinal change in femorotibial cartilage thickness and subchondral bone
      plate area in male and female adolescent vs. mature athletes.
AB  - Little is known about changes in human cartilage thickness and subchondral bone
      plate area (tAB) during growth. The objective of this study was to explore
      longitudinal change in femorotibial cartilage thickness and tAB in adolescent
      athletes, and to compare these data with those of mature former athletes. Twenty
      young (baseline age 16.0 +/- 0.6 years) and 20 mature (46.3 +/- 4.7 years)
      volleyball athletes were studied (10 men and 10 women in each group). Magnetic
      resonance images were acquired at baseline and at year 2-follow-up, and
      longitudinal changes in cartilage thickness and tAB were determined
      quantitatively after segmentation. The yearly increase in total femorotibial
      cartilage thickness was 0.8% (95% confidence interval [CI]: -0.5; 2.1%) in young
      men and 1.4% (95% CI: 0.7; 2.2%) in young women; the gain in tAB was 0.4% (95%
      CI: -0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%), respectively (no significant
      difference between sexes). The cartilage thickness increase was greatest in the
      medial femur, and was not significantly associated with the variability in tAB
      growth (r=-0.19). Mature athletes showed smaller gains in tAB, and lost >1% of
      femorotibial cartilage per annum, with the greatest loss observed in the lateral
      tibia. In conclusion, we find an increase in cartilage thickness (and some in
      tAB) in young athletes toward the end of adolescence. This increase appeared
      somewhat greater in women than men, but the differences between both sexes did
      not reach statistical significance. Mature (former) athletes displayed high rates
      of (lateral) femorotibial cartilage loss, potentially due to a high prevalence of
      knee injuries.

PMID- 24439996
TI  - Neoadjuvant intra-arterial chemotherapy followed by total laparoscopic radical
      trachelectomy in stage IB1 cervical cancer.
AB  - OBJECTIVE: To support the feasibility and safety of neoadjuvant intra-arterial
      chemotherapy followed by total laparoscopic radical trachelectomy in stage IB1
      cervical cancer with tumor larger than 2 cm. DESIGN: A retrospective study.
      SETTING: University-affiliated gynecologic oncology department. PATIENT(S):
      Patients with stage IB1 cervical cancer with tumor size larger than 2 cm who wish
      to preserve fertility. INTERVENTION(S): Neoadjuvant intra-arterial chemotherapy
      followed by laparoscopic radical trachelectomy. MAIN OUTCOMES MEASURE(S): Data
      regarding neoadjuvant chemotherapy operational time, blood loss, recurrence, and
      subsequent pregnancies were recorded. Other published reports on neoadjuvant
      chemotherapy followed by radical trachelectomy were reviewed. RESULT(S): Seven
      patients had a laparoscopic radical trachelectomy after neoadjuvant intra
      arterial chemotherapy for stage IB1 cervical cancer. Median tumor diameter
      evaluated by colposcopy was 3.3 cm (range, 2.5-4.0 cm), tumor histotype was all
      squamous. All patients showed complete or partial response to neoadjuvant
      chemotherapy, and they were all treated with total laparoscopic radical
      trachelectomy. One patient had no menses after treatment. After a median 66
      months (range, 12-90 months) of follow-up time, no recurrence was observed. Only
      four patients attempted to conceive and two succeeded. CONCLUSION(S): Neoadjuvant
      intra-arterial chemotherapy followed by total laparoscopic radical trachelectomy
      may become a useful option for women with cervical cancer with a tumor size
      larger than 2 cm who wish to preserve fertility. Ovarian protection warrants
      further investigation.

PMID- 24439997
TI  - Computed tomography evaluation in total knee arthroplasty: computer-assisted
      navigation versus conventional instrumentation in patients with advanced valgus
      arthritic knees.
AB  - Arthritic knees with advanced valgus deformity present with soft tissue and
      osseous anomalies that make total knee arthroplasty (TKA) difficult. We conducted
      a retrospective chart review of 41 patients (51 knees) to determine whether
      computer-assisted surgery-TKA (CAS-TKA) is superior to TKA using conventional
      guiding systems. A significantly higher rate of lateral retinaculum release as
      well as outlier of sagittal mechanical axes and position of the femoral component
      (femoral flexion and femoral rotational angle) was recorded in the conventional
      TKA group versus the CAS-TKA group. Both groups had significant postoperative
      improvement in clinical performance, but results did not differ significantly
      between groups. Despite its radiographic benefit, CAS-TKA showed no significant
      benefit over TKA in short-term clinical functional outcomes when performed by an
      experienced surgeon.

PMID- 24439998
TI  - Intra-articular bupivacaine reduces postoperative pain and meperidine use after
      total hip arthroplasty: a randomized, double-blind study.
AB  - One hundred patients receiving unilateral total hip arthroplasty (THA) were
      randomized to receive an intra-articular injection of 300mg bupivacaine or normal
      saline after completion of surgery. Pain scores of the bupivacaine group were
      significantly lower than those of the control group the first 12hours
      postoperatively (all, P<0.001). A significantly lower dose of meperidine was used
      in the study group than in the control group the first 24hours postoperatively
      (median, 25 vs. 45mg, P<0.001). Nineteen patients in the study group required
      meperidine the first day after surgery, as compared to 45 patients in the control
      group. We conclude that intra-articular injection of bupivacaine after THA
      reduces pain and meperidine use in the first 12hours after surgery.

PMID- 24439999
TI  - Can plate osteosynthesis of periprosthethic femoral fractures cause cement mantle
      failure around a stable hip stem? A biomechanical analysis.
AB  - Periprosthetic femoral fractures (PFF) are a serious complication after total hip
      arthroplasty. Plate fixation with screws perforating the cement mantle is a
      common treatment option. The study objective was to investigate hip stem
      stability and cement mantle integrity under dynamic loading. A cemented hip stem
      was implanted in 17 composite femur models. Nine bone models were osteotomised
      just distal to the stem and fixed with a polyaxial locking plate the other eight
      constructs served as the control group. All specimens were tested in a bi-axial
      material testing machine (100000 cycles). There were no statistically significant
      differences in axial nor in medial (varus) stem migration. No cement cracks were
      detected in both groups. Plate fixation of a PFF with a stable, cemented
      prosthesis did not lead to cement mantle failure in this in vitro study. 

PMID- 24440000
TI  - [Off-label use of misoprostol in obstetrics and gynecology: Introduction].

PMID- 24440001
TI  - [Misoprostol in case of termination of pregnancy in the second and third
      trimesters. Trials].
AB  - Termination of pregnancies (TOP), in the second and third trimesters, require
      feasibility to induce labour with unfavorable cervix. Combination therapy is then
      usually necessary. Misoprostol use is out of marketing authorization in
      obstetrics but is widely used for many years in TOP in the 2nd and 3rd trimesters
      of pregnancy. Most randomized trials comparing misoprostol to other molecules
      available for TOP (gemeprost, dinoprostone, sulprostone) show that misoprostol is
      at least as effective with fewer side effects often especially if using adapted
      doses and routes of administration. Sometimes, products with a marketing
      authorization have been used with caution due to adverse effects more or less
      reported with misoprostol. There is, however, no conclusive evidence in the
      literature showing the superiority of a dose or route of administration of
      misoprostol compared to another. However, sublingual and oral seem to be
      preferred by patients than the vaginal route which remains the most evaluated and
      effective route. In summary, the use of vaginal misoprostol is the first-line
      treatment in medical abortion in the 2nd and third trimester, in combination with
      at least 200mg of mifepristone 36 to 48 hours before, at a dose of 400 MUg every
      4 to 6 hours. However, its use must be given with caution in cases of uterine
      scar, but cannot be forbidden for the sole justification of not having a
      marketing authorization. It will nevertheless warrant information to patients and
      allow a reduction at least half doses. The multi-scarred uterus still justifies a
      lower starting dose in the minimum effective doses (100 MUg or less) as a
      corollary, increased induction-expulsion delay. The risk-benefit balance must be
      discussed with the patient. The agent without any pharmacological action solely
      or in combination (laminar dilapans, Foley catheter or double balloon) is
      particularly interesting in the case of uterine scar or maternal vascular risk
      but requires further evaluation by other research with adequate power and
      methodology before recommending for systematic routine use.

PMID- 24440002
TI  - Pathomechanisms: homeostatic chemokines in health, tissue regeneration, and
      progressive diseases.
AB  - Homeostatic chemokines control stem and progenitor cell migration and activation
      during vasculogenesis and organ development. They orchestrate hematopoietic stem
      cell (HSC) homing to their bone marrow niches and direct immature lymphocytes to
      a series of maturation sites within lymphoid organs. Along these lines,
      homeostatic chemokines regulate the niches of peripheral committed progenitor
      cell populations for tissue renewal. These biological functions support
      neovascularization and wound healing, including the recruitment of endothelial
      and other progenitor cells from the bone marrow. Here, we summarize the roles of
      homeostatic chemokines, their signaling receptors, and atypical decoy receptors
      during homeostasis and tissue regeneration in order to better understand their
      pathogenic roles in disease, for example, in diabetes complications, cancer,
      autoimmunity, epithelial hyperplasia, or hypertrophic scarring and fibrosis. 

PMID- 24440003
TI  - Securing of naso-gastric tubes in adult patients: a review.
AB  - OBJECTIVES: To establish the most effective securing devices and techniques for
      preventing nasogastric tube displacement or inadvertent extubation, mucosa and
      skin lesions, discomfort, and complications (ab ingestis pneumonia, reduced
      caloric intake, mortality) in adult patients. DESIGN: Systematic review of
      published and unpublished reports in any language, identified by searching 5
      electronic databases, websites, reference lists, and existing systematic reviews
      and papers identified by experts in the field. ELIGIBILITY CRITERIA FOR SELECTING
      STUDIES: Systematic reviews, randomised controlled trials, and comparative
      studies that compared >=2 techniques or devices to secure nasogastric tubes in
      patients 18 years old or older. RESULTS: Five studies (of which two were
      randomised controlled trials) were included. Four studies reported on bridle
      versus the tape technique (unbridled). The studies' population was comprised of
      mostly Intensive Care Unit patients. Four studies measured unintentional
      dislodgement or removal and found a statistically significant advantage in favour
      of the bridle. Three studies measured time until failure: two studies compared
      the bridle versus tape technique whereas the other compared different types of
      tape. One study did not find any significant difference between the two groups of
      patients whereas the second demonstrated a significantly longer time until
      failure in the bridled patients. Three studies comparing bridled and unbridled
      patients measured adverse events such as external nasal ulceration, epistaxis and
      sinusitis, and there was no agreement between their results. One study measured
      caloric intake and found that bridled patients received a higher percentage of
      their caloric goal than unbridled patients. Only one study analysed the cost
      effectiveness of the bridle versus the tape technique and found a cost saving by
      implementing routine bridling of nasoenteric feeding tubes. Discomfort was not
      measured in the included studies. CONCLUSIONS: Despite the large number of
      patients receiving this intervention, there is insufficient evidence to suggest
      one securing technique or device over another. Data are lacking on the beneficial
      effects of the various methods or systems. There is little or no statistically
      significant evidence regarding bridling of nasogastric tubes but more research is
      needed. There is a need for more well-designed studies conducted in various
      clinical settings.

PMID- 24440004
TI  - Effect of ivabradine on left ventricular remodelling after reperfused myocardial
      infarction: A pilot study.
AB  - BACKGROUND: Heart rate is a major determinant of myocardial oxygen demand; in ST
      segment elevation myocardial infarction (STEMI), patients treated with primary
      percutaneous intervention (PPCI), heart rate at discharge correlates with
      mortality. Ivabradine is a pure heart rate-reducing agent that has no effect on
      blood pressure and contractility, and can reverse left ventricular (LV)
      remodelling in patients with heart failure. AIMS: To evaluate whether ivabradine,
      when added to current guideline-based therapy, improves LV remodelling in STEMI
      patients treated with PPCI. METHODS: This paired-cohort study included 124
      patients between June 2011 and July 2012. Ivabradine (5mg twice daily) was given
      promptly after PPCI, along with beta-blockers, to obtain a heart rate<60 beats
      per minute (ivabradine group). This group was matched with STEMI patients treated
      in line with current guidelines, including beta-blockers (bisoprolol), according
      to age, sex, infarct-related coronary artery, ischaemia time and infarct size
      determined by initial cardiac magnetic resonance imaging (CMR) (control group).
      Statistical analyses were performed according to an intention-to-continue
      treatment principle. CMR data at 3 months were available for 122 patients.
      RESULTS: Heart rate was lower in the ivabradine group than in the control group
      during the initial CMR (P=0.02) and the follow-up CMR (P=0.006). At the follow-up
      CMR, there was a smaller increase in LV end-diastolic volume index in the
      ivabradine group than in the control group (P=0.04). LV end-systolic volume index
      remained unchanged in the ivabradine group, but increased in the control group
      (P=0.01). There was a significant improvement in LV ejection fraction in the
      ivabradine group compared with in the control group (P=0.04). CONCLUSIONS: In
      successfully reperfused STEMI patients, ivabradine may improve LV remodelling
      when added to current guideline-based therapy.

PMID- 24440005
TI  - Are osseous artefacts a window to perishable material culture? Implications of an
      unusually complex bone tool from the Late Pleistocene of East Timor.
AB  - We report the discovery of an unusually complex and regionally unique bone
      artefact in a Late Pleistocene archaeological assemblage (c. 35 ka [thousands of
      years ago]) from the site of Matja Kuru 2 on the island of Timor, in Wallacea.
      The artefact is interpreted as the broken butt of a formerly hafted projectile
      point, and it preserves evidence of a complex hafting mechanism including
      insertion into a shaped or split shaft, a complex pattern of binding including
      lateral stabilization of the cordage within a bilateral series of notches, and
      the application of mastic at several stages in the hafting process. The artefact
      provides the earliest direct evidence for the use of this combination of hafting
      technologies in the wider region of Southeast Asia, Wallacea, Melanesia and
      Australasia, and is morphologically unparallelled in deposits of any age. By
      contrast, it bears a close morphological resemblance to certain bone artefacts
      from the Middle Stone Age of Africa and South Asia. Examination of ethnographic
      projectile technology from the region of Melanesia and Australasia shows that all
      of the technological elements observed in the Matja Kuru 2 artefact were in use
      historically in the region, including the unusual feature of bilateral notching
      to stabilize a hafted point. This artefact challenges the notion that complex
      bone-working and hafting technologies were a relatively late innovation in this
      part of the world. Moreover, its regional uniqueness encourages us to abandon the
      perception of bone artefacts as a discrete class of material culture, and to
      adopt a new interpretative framework in which they are treated as manifestations
      of a more general class of artefacts that more typically were produced on
      perishable raw materials including wood. 

PMID- 24440006
TI  - A possible cause of Alzheimer's dementia - industrial soy foods.
AB  - Alzheimer's data indicate that at present, approximately one new case of this
      form of dementia is identified in the USA every 68 s and that by 2050 the
      incidence will be about every 33 s, with projections from the Alzheimer
      Association (USA) indicating that nearly 25% of Americans will be affected by
      Alzheimer's dementia by 2031. Despite the numerous advances in medical science
      and neurological research, the causes are still unknown and the incidence is not
      decreasing or levelling out. Most research on the causes of Alzheimer's dementia
      indicates the possible roles of viruses, obesity, physical inactivity, diabetes,
      psychological depression, high blood pressure, frequent inflammation,
      environmental or domestic chemicals and toxins, or inescapable genetic factors.
      Alzheimer's, being the degeneration of parts of the neural pathways in the brain,
      may indeed involve neuro-toxic compounds that can bypass the blood-brain barrier.
      Therefore, it is necessary to examine what is prolific in the environment and, in
      particular, the food supply. One of the many suggestions in the literature is the
      ingestion of food items derived from unfermented soybean products; the anti
      thyroid, anti-nutrient, and endocrine disruption properties of soy can have a
      deleterious effect in many individuals. Among the many theories and different
      factors that may be involved in dementiae, soy consumption may be a significant
      contributor to Alzheimer's dementia, and it cannot be excluded as a possible
      contributing cause. Our hypothesis argues that consumption of soy food products
      may contribute to the increasing incidence of Alzheimer's dementia and other
      dementiae.

PMID- 24440007
TI  - The year in cardiothoracic and vascular anesthesia: selected highlights from
      2013.
AB  - This article reviewed selected research highlights of 2013 that pertain to the
      specialty of cardiothoracic and vascular anesthesia. The first major theme is the
      commemoration of the sixtieth anniversary of the first successful cardiac
      surgical procedure with cardiopulmonary bypass conducted by Dr Gibbon. This major
      milestone revolutionized the practice of cardiovascular surgery and invigorated a
      paradigm of mechanical platforms for contemporary perioperative cardiovascular
      practice. Dr Kolff was also a leading contributor in this area because of his
      important contributions to the refinement of cardiopulmonary bypass and
      mechanical ventricular assistance. The second major theme is the diffusion of
      echocardiography throughout perioperative practice. There are now guidelines and
      training pathways to guide its generalization into everyday practice. The third
      major theme is the paradigm shift in perioperative fluid management. Recent large
      randomized trials suggest that fluids are drugs that require a precise
      prescription with respect to type, dose, and duration. The final theme is patient
      safety in the cardiac perioperative environment. A recent expert scientific
      statement has focused attention on this issue because most perioperative errors
      are preventable. It is likely that clinical research in this area will blossom
      because this is a major opportunity for improvement in our specialty. The patient
      care processes identified in these research highlights will further improve
      perioperative outcomes for our patients. 

PMID- 24440008
TI  - The dynamics of mitral valve function: lessons to be learned from three
      dimensional echocardiography.

PMID- 24440009
TI  - Multinational institutional survey on patterns of intraoperative transesophageal
      echocardiography use in adult cardiac surgery.
AB  - OBJECTIVES: To assess institutional patterns of perioperative transesophageal
      echocardiography (TEE) usage. DESIGN: The authors hypothesized that TEE is
      performed more frequently and comprehensively in academic centers, mainly by
      anesthesiologists, and barriers to performing TEE are due to inadequate
      resources. A survey was deployed to selected participants. Collated responses
      were assessed for demographic patterns in TEE practice, and 2-category
      comparisons were made with Chi-squared association tests. SETTING: Web-based
      survey. PARTICIPANTS: Practitioners in cardiovascular anesthesia/surgery in 200
      institutions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Surveys were
      completed by respondents representing 200 centers in 27 countries and 1,727
      anesthesiologists with a mean annual institutional volume of 924 cases. Most
      centers were in the USA (53%) and were defined as academic (83%).
      Anesthesiologists performed (85%) and also read/reported TEEs (78%) in most
      centers. Three-dimensional TEE is performed routinely at 40% of centers. TEE is
      used routinely for valve surgery in 95% of institutions compared to 68% for
      coronary artery bypass graft surgery. Academic institutions assessed diastolic
      function more often than nonacademic centers (46% v 19%; p = 0.006). The most
      important reason cited for not using TEE in all cases was insufficient resource
      availability (47%). CONCLUSIONS: These results suggest that TEE is performed more
      comprehensively in academic centers, mainly by anesthesiologists, and that lack
      of resources is a significant barrier to routine TEE usage. TEE is used more
      often for valve surgery than for coronary artery bypass graft surgery, and many
      centers use 3D TEE. This survey describes international TEE practice patterns and
      identifies limitations to universal adoption of TEE in cardiac surgery.

PMID- 24440010
TI  - Incidental moderate mitral regurgitation in patients undergoing coronary artery
      bypass grafting: update on guidelines and key randomized trials.
AB  - Incidental moderate mitral regurgitation (MR) in patients presenting for coronary
      artery bypass grafting (CABG) is not only common but also probably adversely
      affects clinical outcome. The echocardiographic evaluation of incidental MR must
      be comprehensive and integrated, as it remains a cornerstone in management
      decisions. Current guidelines support surgical mitral intervention in this
      setting as a reasonable option, reflecting clinical equipoise towards moderate MR
      in the setting of planned CABG. There are currently 2 major randomized trials in
      progress that will test whether surgical correction of moderate MR combined with
      CABG improves major clinical outcomes as compared to CABG alone. These landmark
      trials will be completed in the near future. In the interim, significant progress
      in the fields of cardiac resynchronization therapy, transcatheter mitral valve
      intervention, and minimally invasive mitral valve surgery promise to affect the
      management alternatives for moderate MR in patients undergoing CABG regardless of
      operative risk. It is likely that in the coming decade there will be less
      tolerance for incidental moderate MR given its already known outcome effects and
      the multimodal interventions that continue to mature with better safety profiles.

PMID- 24440011
TI  - A coronary artery fistula successfully closed with the precise guidance of three
      dimensional echocardiography.

PMID- 24440012
TI  - Three-dimensional transesophageal echocardiography: more than just pretty
      pictures.

PMID- 24440013
TI  - Planting the seed: target recognition of short guide RNAs.
AB  - Small guide RNAs play important roles in cellular processes such as regulation of
      gene expression and host defense against invading nucleic acids. The mode of
      action of small RNAs relies on protein-assisted base pairing of the guide RNA
      with target mRNA or DNA to interfere with their transcription, translation, or
      replication. Several unrelated classes of small noncoding RNAs have been
      identified including eukaryotic RNA silencing-associated small RNAs, prokaryotic
      small regulatory RNAs (sRNAs), and prokaryotic CRISPR (clustered regularly
      interspaced short palindromic repeats) RNAs (crRNAs). All three groups identify
      their target sequence by base pairing after finding it in a pool of millions of
      other nucleotide sequences in the cell. In this complicated target search
      process, a region of 6-12 nucleotides (nt) of the small RNA termed the 'seed'
      plays a critical role. We review the concept of seed sequences and discuss its
      importance for initial target recognition and interference. 

PMID- 24440014
TI  - Cardiopulmonary responses to robotic end-effector-based walking and stair
      climbing.
AB  - BACKGROUND: A recently developed robotic end-effector device (G-EO system, Reha
      Technology AG) can simulate walking and stair climbing. This approach has the
      potential to promote cardiovascular exercise training during rehabilitation. The
      aim of this study was to characterise cardiopulmonary responses of end-effector
      based exercise in able-bodied subjects and to evaluate the feasibility of
      intensity-guided exercise testing. METHODS: Five healthy subjects aged 33.7 +/-
      8.8 years (mean +/- SD) performed a constant load test and an intensity-guided
      incremental exercise test. The outcome measures were steady-state and peak
      cardiopulmonary performance parameters including oxygen uptake (VO2) and heart
      rate (HR). RESULTS: Passive end-effector-based stair climbing (VO2=13.6 +/- 4.5
      mL/min/kg, HR=95 +/- 23 beats/min) showed considerably lower cardiopulmonary
      responses compared to reference data (VO2=33.5 +/- 4.8 mL/min/kg, HR=159 +/- 15
      beats/min). Peak performance parameters during intensity-guided incremental
      exercise testing were: VO2=35.8 +/- 5.1 mL/min/kg and HR=161 +/- 27 beats/min,
      corresponding to a relative VO2=76.0 +/- 18.7% of predicted aerobic capacity and
      a relative HR=87.3 +/- 14.5% of age-predicted HR maximum. CONCLUSION: End
      effector-based exercise is a promising method for the implementation of
      cardiovascular exercise. Although end-effector-based stair climbing evoked lower
      cardiopulmonary responses than conventional stair climbing, active contribution
      during exercise elicited substantial cardiopulmonary responses within recommended
      ranges for aerobic training.

PMID- 24440016
TI  - Effect of valve design on the stent internal diameter of a bioprosthetic valve: a
      concept of true internal diameter and its implications for the valve-in-valve
      procedure.
AB  - The goal of this study was to provide a measurement of the true internal diameter
      (ID) of various surgical heart valves (SHV) to facilitate the valve-in-valve
      (VIV) procedure. During a VIV procedure, it is important to choose the right of
      the transcatheter heart valve (THV). Most users use the stent ID of an SHV to
      select the appropriate THV size. Echocardiography and computed tomography
      measurements are not yet standardized for measuring the ID of a variety of SHVs.
      Hence, we measured the true ID of SHV to assess the effect of valve design on the
      stent ID. Thirteen types of stented and 3 types of stentless valves were
      evaluated. True ID measurements were obtained using calipers and Hegar dilators.
      These were compared with the stent ID measurements. Fluoroscopy was used to
      confirm the impact of SHV designs on the true ID. Caliper measurements were found
      to be inaccurate and are hence not recommended. Hegar dilator measurements
      revealed a trend of reduction in stent ID. Porcine valves were most affected by
      their design, with reduction in the stent ID by at least 2 mm; pericardial valves
      with leaflets sutured inside the stent had the stent ID reduced by at least 1 mm,
      and SHV with leaflets sutured outside the stent had no effect on stent ID. In the
      majority of SHV designs, there is a reduction in the stent ID as a result of
      leaflet tissue. This is important in borderline sizes to avoid problems
      associated with oversizing and also to confirm suitability for the VIV procedure
      in the smaller label sizes of SHV. 

PMID- 24440015
TI  - Predicting outcome in the COURAGE trial (Clinical Outcomes Utilizing
      Revascularization and Aggressive Drug Evaluation): coronary anatomy versus
      ischemia.
AB  - OBJECTIVES: The aim of this study was to determine the relative utility of
      anatomic and ischemic burden of coronary artery disease for predicting outcomes.
      BACKGROUND: Both anatomic burden and ischemic burden of coronary artery disease
      determine patient prognosis and influence myocardial revascularization decisions.
      When both measures are available, their relative utility for prognostication and
      management choice is controversial. METHODS: A total of 621 patients enrolled in
      the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug
      Evaluation) trial with baseline quantitative nuclear single-photon emission
      computed tomography (SPECT) and quantitative coronary angiography were studied.
      Several multiple regression models were constructed to determine independent
      predictors of the endpoint of death, myocardial infarction (MI) (excluding
      periprocedural MI) and non-ST-segment elevation acute coronary syndromes (NSTE
      ACS). Ischemic burden during stress SPECT, anatomic burden derived from
      angiography, left ventricular ejection fraction, and assignment to either optimal
      medical therapy (OMT) + percutaneous coronary intervention (PCI) or OMT alone
      were analyzed. RESULTS: In nonadjusted and adjusted regression models, anatomic
      burden and left ventricular ejection fraction were consistent predictors of
      death, MI, and NSTE-ACS, whereas ischemic burden and treatment assignment were
      not. There was a marginal (p = 0.03) effect of the interaction term of anatomic
      and ischemic burden for the prediction of clinical outcome, but separately or in
      combination, neither anatomy nor ischemia interacted with therapeutic strategy to
      predict outcome. CONCLUSIONS: In a cohort of patients treated with OMT, anatomic
      burden was a consistent predictor of death, MI, and NSTE-ACS, whereas ischemic
      burden was not. Importantly, neither determination, even in combination,
      identified a patient profile benefiting preferentially from an invasive
      therapeutic strategy. (Clinical Outcomes Utilizing Revascularization and
      Aggressive Drug Evaluation [COURAGE]; NCT00007657).

PMID- 24440017
TI  - Prevention of cerebral embolization by placing a neuroprotection filter before
      recoarctation stent dilation.

PMID- 24440018
TI  - Is it form or function?: the "COURAGE" to ask.

PMID- 24440019
TI  - Left bundle branch block after transcatheter aortic valve implantation: still a
      matter of concern?

PMID- 24440020
TI  - Contemporary carotid stenting: comparative effectiveness research from the NCDR
      (National Cardiovascular Data Registry).

PMID- 24440021
TI  - Acute myocardial infarction after left-heart catheterization in a patient with
      severe calcified bicuspid aortic stenosis.

PMID- 24440022
TI  - Anatomical eligibility of the renal vasculature for catheter-based renal
      denervation in hypertensive patients.
AB  - OBJECTIVES: This study sought to determine the vascular anatomical eligibility
      for catheter-based renal artery denervation (RDN) in hypertensive patients.
      BACKGROUND: Arterial hypertension is the leading cardiovascular risk factor for
      stroke and mortality globally. Despite substantial advances in drug-based
      treatment, many patients do not achieve target blood pressure levels. To improve
      the number of controlled patients, novel procedure- and device-based strategies
      have been developed. RDN is among the most promising novel techniques. However,
      there are few data on the vascular anatomical eligibility. METHODS: We
      retrospectively analyzed 941 consecutive hypertensive patients undergoing
      coronary angiography and selective renal artery angiography between January 1,
      2010, and May 31, 2012. Additional renal arteries were divided into 2 groups:
      hilar (accessory) and polar (aberrant) arteries. Anatomical eligibility for RDN
      was defined according to the current guidelines: absence of renal artery
      stenosis, renal artery diameter >=4 mm, renal artery length >=20 mm, and only 1
      principal renal artery. RESULTS: A total of 934 hypertensive patients were
      evaluable. The prevalence of renal artery stenosis was 10% (n = 90). Of the
      remaining 844 patients without renal artery stenosis, 727 (86%) had nonresistant
      hypertension and 117 (14%) had resistant hypertension; 62 (53%) of the resistant
      hypertensive and 381 (52%) of the nonresistant hypertensive patients were
      anatomically eligible for sympathetic RDN. CONCLUSIONS: The vascular anatomical
      eligibility criteria of the current guidelines are a major limiting factor for
      the utilization of RDN as a therapeutic option. Development of new devices and/or
      techniques may significantly increase the number of candidates for these
      promising therapeutic options.

PMID- 24440023
TI  - Anatomical exclusion for renal denervation: are we putting the cart before the
      horse?

PMID- 24440024
TI  - Impact of new-onset persistent left bundle branch block on late clinical outcomes
      in patients undergoing transcatheter aortic valve implantation with a balloon
      expandable valve.
AB  - OBJECTIVES: The aim of this study was to determine the impact of new-onset
      persistent left bundle branch block (NOP-LBBB) on late outcomes after
      transcatheter aortic valve implantation (TAVI). BACKGROUND: The impact of NOP
      LBBB after TAVI remains controversial. METHODS: A total of 668 consecutive
      patients who underwent TAVI with a balloon-expandable valve without pre-existing
      LBBB or permanent pacemaker implantation (PPI) were included. Electrocardiograms
      were obtained at baseline, immediately after the procedure, and daily until
      hospital discharge. Patients were followed at 1, 6, and 12 months and yearly
      thereafter. RESULTS: New-onset LBBB occurred in 128 patients (19.2%) immediately
      after TAVI and persisted at hospital discharge in 79 patients (11.8%). At a
      median follow-up of 13 months (range 3 to 27 months), there were no differences
      in mortality rate between the NOP-LBBB and no NOP-LBBB groups (27.8% vs. 28.4%;
      adjusted-hazard ratio: 0.87 [95% confidence interval (CI): 0.55 to 1.37]; p =
      0.54). There were no differences between groups regarding cardiovascular
      mortality (p = 0.82), sudden death (p = 0.87), rehospitalizations for all causes
      (p = 0.11), or heart failure (p = 0.55). NOP-LBBB was the only factor associated
      with an increased rate of PPI during the follow-up period (13.9% vs. 3.0%; hazard
      ratio: 4.29 [95% CI: 2.03 to 9.07], p < 0.001. NOP-LBBB was also associated with
      a lack of left ventricular ejection fraction improvement and poorer New York
      Heart Association functional class at follow-up (p < 0.02 for both). CONCLUSIONS:
      NOP-LBBB occurred in ~1 of 10 patients who had undergone TAVI with a balloon
      expandable valve. NOP-LBBB was associated with a higher rate of PPI, a lack of
      improvement in left ventricular ejection fraction, and a poorer functional
      status, but did not increase the risk of global or cardiovascular mortality or
      rehospitalizations at 1-year follow-up.

PMID- 24440025
TI  - Comparative effectiveness of commonly used devices for carotid artery stenting:
      an NCDR Analysis (National Cardiovascular Data Registry).
AB  - OBJECTIVES: This study sought to characterize usage and outcomes of carotid
      stenting platforms. BACKGROUND: A variety of stents and embolic protection
      devices (EPDs) are used for carotid artery stenting. Little is known about
      current usage patterns and differences in outcomes with these devices. METHODS:
      We analyzed 12,135 consecutive carotid stent procedures in the NCDR (National
      Cardiovascular Data Registry) CARE (Carotid Artery Revascularization and
      Endarterectomy) registry performed between January 1, 2007 and March 31, 2012. We
      compared baseline characteristics and crude and multivariable-adjusted rates of
      in-hospital combined death/stroke among patients treated with Acculink/Accunet
      (Abbott Laboratories, Abbott Park, Illinois), Xact/Emboshield (Abbott), and
      Precise/Angioguard (Cordis Corporation, Bridgewater, New Jersey) stent/EPD
      combinations. RESULTS: In 78.2% of cases, stents were used in conjunction with
      their specific, corresponding U.S. Food and Drug Administration-approved EPD. The
      Acculink/Accunet (n = 2,617, 21.6%), Xact/Emboshield (n = 3,507, 28.9%), and
      Precise/Angioguard (n = 2,696, 22.2%) stent/EPD combinations were used in 72.7%
      of all cases. The Protege/SpiderFx (ev3 Endovascular Inc., Plymouth, Minnesota)
      (n = 453, 3.7%) and Wallstent/Filterwire (Boston Scientific, Natick,
      Massachusetts) (n = 213, 1.8%) devices were used in a minority of cases. In
      unadjusted analyses, the Precise/Angioguard system was associated with higher
      rates of the primary outcome than were the Acculink/Accunet (2.5% vs. 1.8%; p =
      0.058) and Xact/Emboshield (2.5% vs. 1.9%; p = 0.14) systems that were not
      statistically different. In adjusted analyses, differences between
      Precise/Angioguard and Accunet/Acculink (odds ratio [OR]: 1.48, 95% confidence
      interval [CI]: 0.89 to 2.47; p = 0.065), Precise/Angioguard and Xact/Emboshield
      (OR: 1.16, 95% CI: 0.77 to 1.76; p = 0.38), and Xact/Emboshield and
      Accunet/Acculink (OR: 1.28, 95% CI: 0.82 to 1.97; p = 0.18) remained
      nonsignificant. CONCLUSIONS: In modern U.S. practice, the Acculink/Accunet,
      Xact/Emboshield, and Precise/Angioguard carotid stenting systems are used in most
      cases and are associated with similarly low rates of adverse events.

PMID- 24440026
TI  - Immediate results and long-term clinical outcome of patients with unprotected
      distal left main restenosis: the CORPAL registry (Cordoba and Las Palmas).
AB  - OBJECTIVES: The goal of this study was to assess the immediate and long-term
      outcomes in patients undergoing percutaneous coronary intervention (PCI) for in
      stent restenosis (ISR) in an unprotected distal left main coronary artery (UDLM).
      BACKGROUND: PCI for UDLM-ISR can be complex. Limited information is available on
      procedural and clinical outcomes. METHODS: Between May 2002 and February 2011,
      UDLM-ISR after drug-eluting stent implantation was observed in 79 of 1,102
      patients (7%). Seventy-five were treated by repeat PCI using a simple approach
      (balloon/in-stent implantation) or a complex strategy (additional stent/double
      stenting technique). A diagnosis of mild or severe restenosis was considered
      depending on the number of bifurcation segments affected (1 vs. >1). Major
      adverse cardiac events (MACE) were defined as cardiac death, target lesion
      revascularization, and myocardial infarction. RESULTS: ISR treatment was
      performed using a simple approach in 44 (58%) patients, and using a complex
      strategy in 31 (42%). After 46 +/- 26 months, the MACE rate was 22%. Patients
      treated with a simple approach had a lower incidence of MACE at follow-up
      compared with patients treated with a complex strategy, regardless of the
      restenosis extent (mild restenosis: 93% vs. 67%, p < 0.05; severe: 70% vs. 23%, p
      < 0.05). On Cox regression analysis, diabetes was the only predictor of MACE
      (hazard ratio [HR]: 4.94; 95% confidence interval [CI]: 1.03 to 23.70; p < 0.05),
      whereas a simple strategy for ISR treatment was associated with lower risk (HR:
      0.25; 95% CI: 0.08 to 0.79; p = 0.02). CONCLUSIONS: PCI for UDLM-ISR is safe and
      feasible, with a high rate of procedural success and an acceptable long-term MACE
      rate. A simple strategy, when applicable, appears to be a good treatment option,
      associated with a lower event rate at follow-up.

PMID- 24440027
TI  - Spontaneous right coronary artery dissection: a case of spontaneous resolution.

PMID- 24440028
TI  - Lessons learned from thermosensitive liposomes for improved chemotherapy.

PMID- 24440029
TI  - Bilateral radiolucent lesions of the jaw in a generalized periodontitis patient.
      Central giant cell granuloma.

PMID- 24440030
TI  - [Zygomatic arch fracture extended to the glenoid fossa: a cause of TMJ pain].
AB  - INTRODUCTION: Fractures of the zygomatic arch extended to the glenoid fossa are
      rare and seldom reported. OBSERVATION: A 26-year-old man with a slightly
      dislocated fracture of the zygoma associated with trismus, and localized pain in
      the right Temporo-Mandibular Joint (TMJ) on palpation, but without any condylar
      fracture. The craniofacial CT scan revealed a fracture of the zygoma extended to
      the glenoid fossa. The treatment was an intraoral reduction of the zygoma and
      screw fixation of the glenoid fossa lateral region. DISCUSSION: The risk of
      delayed healing by mobilization of the bone fragments was opposed to the risk of
      TMJ ankylosis due to a prolonged immobilization of the joint. Osteosynthesis of
      the fracture was finally chosen.

PMID- 24440031
TI  - [Comments about: "Surgical treatment of obstructive sleep apnea syndrome.
      Functional assessment"].

PMID- 24440032
TI  - Outcomes in idiopathic pulmonary fibrosis: a meta-analysis from placebo
      controlled trials.
AB  - BACKGROUND: Most data on outcomes in Idiopathic Pulmonary Fibrosis (IPF) pre
      dates current guidelines. Data on rates of infection is sparse; the effect of low
      dose corticosteroids and disease severity is unknown. METHODS: We identified
      randomised-controlled trials of IPF and analysed rates of mortality, lower
      respiratory tract infections (LRTIs), IPF progression and acute exacerbations
      from the placebo arms. We standardised event rates and compared differences using
      incidence rate ratios (IRRs) between subgroups according to disease severity or
      use of low-dose immunosuppression. RESULTS: Mortality was lower in trials that
      recruited patients with mild-moderate disease severities only, as compared to
      trials where patients with severe disease were allowed (188.6 vs 78.6 deaths per
      1000 patient/years, IRR 0.30-0.59, p < 0.0001). No statistical difference was
      seen between trials permitting and excluding low-dose prednisolone use. LRTIs
      were found to be commoner in trials allowing low dose prednisolone use compared
      with those that did not (227.1 vs 63.4 infections per 1000 patient/years. IRR
      2.56-5.13, p < 0.0001), and were less frequent in trials excluding patients with
      severe disease (153.9 vs 257.8 infections per 1000 patient/years, IRR 0.45-0.81,
      p = 0.0003). Acute exacerbations occurred less frequently in trials excluding
      severe disease (28.2 vs 122.9 exacerbations per 1000 patient/years, IRR 0.11
      0.55, p < 0.0001). There was no difference between groups in rates of IPF
      progression. CONCLUSION: Mortality is heterogeneous and dependent on entry
      criteria. Infection rates were high, both with and without immunosuppression, and
      were higher in severe disease. Consideration should be given to alternative
      outcomes to mortality in future IPF trials if severe disease is excluded.

PMID- 24440033
TI  - Propofol for pediatric tracheal intubation with deep anesthesia during
      sevoflurane induction: dosing according to elapsed time for two age groups.
AB  - STUDY OBJECTIVE: To determine, for two different age groups, the effect of
      duration of sevoflurane administration on the amount of propofol needed when
      performing tracheal intubation. DESIGN: Classic Dixon's Up-and-Down sequential
      method. SETTING: University based operating rooms. PATIENTS: 106 ASA physical
      status 1 and 2 patients aged one to 11 years. INTERVENTIONS: Patients were
      allocated to the 1-6 year (>= 12 and < 72 mos) and 6-11 year (>= 72 and < 132
      mos) age groups. Midazolam 0.5 mg/kg was given orally to the 1-6 year group, and
      all patients were induced with 8% dialed sevoflurane and 67% nitrous oxide (N2O),
      with N2O discontinued and sevoflurane dialed to 5% after one minute and 1.5
      minutes for the younger and older age groups, respectively. Intravenous access
      was obtained and propofol was promptly administered. Propofol dose was determined
      according to age group and whether propofol was given 2-4, 4-6, or 6-8 minutes
      after the start of sevoflurane induction, with Dixon's Up and Down Method used
      separately for each specific age/time group. Tracheal intubation conditions one
      minute after propofol were evaluated. MEASUREMENTS: Isotonic regression
      determined propofol ED50 estimates for excellent tracheal intubation conditions,
      and linear regression determined the effect of propofol dose on change in
      systolic blood pressure (SBP). MAIN RESULTS: Estimated propofol ED50 doses for 1
      6 year olds, with 95% confidence intervals (CIs), were 1.48 mg/kg (0.80, 2.03),
      0.00 mg/kg (0.00, 0.38), and 0.07 mg/kg (0.00, 0.68) in the 2-4, 4-6, and 6-8
      minute groups, respectively, with estimated differences between the 2-4 minute
      group versus the 4-6 and 6-8 minute groups being 1.47 mg/kg (95% CI = 1.04, 2.06)
      and 1.41 mg/kg (95% CI = 0.74, 2.04), respectively. Estimated propofol ED50 doses
      for 6-11 year olds, with 95% CIs, were 2.35 mg/kg (1.97, 2.45) and 2.33 mg/kg
      (1.59, 2.45) in the 2-4 and 4-6 minute groups, respectively. Diminutions in SBP
      at one minute and two minutes after propofol administration were dose dependent
      for children 1-6 years of age, decreasing 5.3% and 8.1% for each 1 mg/kg of
      propofol, respectively. CONCLUSION: The amount of propofol needed to supplement
      sevoflurane in children 1-6 years of age can be expected to decrease after 4
      minutes of sevoflurane.

PMID- 24440034
TI  - Perioperative considerations in the patient with Angelman syndrome.
AB  - Angelman syndrome arises by one of 4 genetic mechanisms. Patients often have
      craniofacial abnormalities, vagal hypertonia, skeletal muscle atrophy or
      underdevelopment, a history of seizure disorders, and pharmacodynamic
      unpredictability. Its pathogenesis, clinical manifestations, diagnosis and
      treatment options, and perioperative anesthetic considerations are presented. 

PMID- 24440035
TI  - A delayed case of tension pneumopericardium after total gastrectomy.
AB  - A case of tension pneumopericardium that occurred after total gastrectomy in an
      80 year old woman is presented. There have been some prior case reports of
      pneumopericardium that occurred during positive pressure ventilation; in this
      patient hypotension due to tension pneumopericardium occurred after extubation.
      Return of spontaneous ventilation with negative-pressure breathing may have
      induced air aspiration into the pericardial sac from the abdominal cavity. 

PMID- 24440036
TI  - Adaptive capacity to bacterial diet modulates aging in C. elegans.
AB  - Diet has a substantial impact on cellular metabolism and physiology. Animals must
      sense different food sources and utilize distinct strategies to adapt to diverse
      diets. Here we show that Caenorhabditis elegans lifespan is regulated by their
      adaptive capacity to different diets, which is controlled by alh-6, a conserved
      proline metabolism gene. alh-6 mutants age prematurely when fed an Escherichia
      coli OP50 but not HT115 diet. Remarkably, this diet-dependent aging phenotype is
      determined by exposure to food during development. Mechanistically, the alh-6
      mutation triggers diet-induced mitochondrial defects and increased generation of
      ROS, likely due to accumulation of its substrate 1-pyrroline-5-carboxylate. We
      also identify that neuromedin U receptor signaling is essential for diet-induced
      mitochondrial changes and premature aging. Moreover, dietary restriction requires
      alh-6 to induce longevity. Collectively, our data reveal a homeostatic mechanism
      that animals employ to cope with potential dietary insults and uncover an example
      of lifespan regulation by dietary adaptation. 

PMID- 24440037
TI  - The therapeutic potential of nuclear receptor modulators for treatment of
      metabolic disorders: PPARgamma, RORs, and Rev-erbs.
AB  - Nuclear receptors (NRs) play central roles in metabolic syndrome, making them
      attractive drug targets despite the challenge of achieving functional
      selectivity. For instance, members of the thiazolidinedione class of insulin
      sensitizers offer robust efficacy but have been limited due to adverse effects
      linked to activation of genes not involved in insulin sensitization. Studies
      reviewed here provide strategies for targeting subsets of PPARgamma target genes,
      enabling development of next-generation modulators with improved therapeutic
      index. Additionally, emerging evidence suggests that targeting the NRs ROR and
      Rev-erb holds promise for treating metabolic syndrome based on their involvement
      in circadian rhythm and metabolism. 

PMID- 24440039
TI  - Time trends between 1987 and 2007 for perfluoroalkyl acids in plasma from Swedish
      women.
AB  - Perfluoroalkyl acids (PFAAs) are a large group of chemicals which are highly
      persistent in both nature and humans. The use of the most prominent ones,
      perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), was reduced
      in the early 21st century, and since then levels in human matrices have
      decreased. However, these two compounds have been exchanged by other PFAAs, for
      which time trends have not been as extensively investigated. By the use of 80
      plasma samples collected between 1987 and 2007 from healthy women (n=1-9 yearly
      for 1987-2001, n=15 from 2006, and n=10 from 2007), possible time trends of six
      PFAAs were assessed. Time trends were evaluated for the entire study period, as
      well as for three sub-periods. As seen in previous studies, levels of
      perfluorohexane sulfonate (PFHxS), PFOS, and PFOA peaked during the middle time
      period (1990-2000), with medians of 0.98 ng mL(-1), 18.06 ng mL(-1), and 3.73 ng
      mL(-1), respectively. However, levels of perfluorononanic acid (PFNA),
      perfluorodecanic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) increased
      over the whole study period and most markedly so after year 2000, with medians of
      0.73 ng mL(-1), 0.28 ng mL(-1), and 0.24 ng mL(-1), respectively, during the last
      study period.

PMID- 24440040
TI  - Ozone reaction characteristics of indoor floor dust examined in the emission cell
      "FLEC".
AB  - Ozone reacts with C-C double bonds in common indoor VOCs and SVOCs contained in
      indoor dust and may be catalytically degraded on dust surfaces. The reaction
      between floor dust and ozone was investigated in the FLEC emission cell at
      different ozone concentrations and relative humidities (0%, 25%, and 50% RH). One
      gram of dust was spread on a clean stainless steel plate which was placed in the
      FLEC. Steady state reaction rate (kDust) at 2.2 ppm ozone was determined for four
      different floor dust samples collected in Danish homes and offices. This high
      concentration was necessary in order to measure and determine the consumption in
      the outlet air from the FLEC. Measurements were corrected for FLEC wall effects
      by subtraction of the steady state reaction rate between ozone and a FLEC on a
      stainless steel plate without dust (kFLEC). The composition of organic compounds
      in the dust was analyzed by pressurized liquid extraction and thermal desorption
      GC-MS before and after ozone exposure. kFLEC was independent of the ozone
      concentration and the reaction was treated as first order. The same was indicated
      for kDust since it remained unchanged at 2.2 and 1.6 ppm ozone for one dust
      sample. However, the measured kDust in the FLEC should be considered an average
      rate constant due to the FLEC geometry. kDust was in the range 0.039-0.14s(-1)
      pr. g dust at 50% RH. kDust was 3 times higher at 25% RH than at 50% RH and 6
      times higher than at 0% RH. The inhomogeneity of the dust was assessed by
      experiments in triplicate with a new portion of dust each time. The relative
      standard deviation of kDust at 50% RH was 6-20%. The major identified compounds
      before and after ozone exposure included aldehydes, saturated and unsaturated
      linear alkanoic acids, benzoic acid and their methyl esters, dimethyl esters,
      phthalates and traces of alpha-pinene and limonene. Substantial increase of C7-C9
      aldehydes was observed after ozone exposure.

PMID- 24440038
TI  - Fasting: molecular mechanisms and clinical applications.
AB  - Fasting has been practiced for millennia, but, only recently, studies have shed
      light on its role in adaptive cellular responses that reduce oxidative damage and
      inflammation, optimize energy metabolism, and bolster cellular protection. In
      lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming
      metabolic and stress resistance pathways. In rodents intermittent or periodic
      fasting protects against diabetes, cancers, heart disease, and neurodegeneration,
      while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid
      arthritis. Thus, fasting has the potential to delay aging and help prevent and
      treat diseases while minimizing the side effects caused by chronic dietary
      interventions. 

PMID- 24440041
TI  - Mapping metabolic changes associated with early Radiation Induced Lung Injury
      post conformal radiotherapy using hyperpolarized 13C-pyruvate Magnetic Resonance
      Spectroscopic Imaging.
AB  - PURPOSE: Radiation Pneumonitis (RP) limits radiotherapy. Detection of early
      metabolic changes in the lungs associated with RP may provide an opportunity to
      adjust treatment before substantial toxicities occur. In this work, regional
      lactate-to-pyruvate signal ratio (lac/pyr) was quantified in rat lungs and heart
      following administration of hyperpolarized (13)C-pyruvate magnetic resonance
      imaging (MRI) at day 5, 10, 15 and 25-post conformal radiotherapy. These results
      were also compared to histology and blood analyses. METHODS: The lower right
      lungs of 12 Sprague Dawley rats were irradiated in 2 fractions with a total dose
      of 18.5 Gy using a modified micro-CT system. Regional lactate and pyruvate data
      were acquired from three irradiated and three age-matched healthy rats at each
      time point on days 5, 10, 15 and 25-post radiotherapy. Arterial blood was
      collected from each animal prior to the (13)C-pyruvate injection and was analyzed
      for blood lactate concentration and arterial oxygen concentration (paO2).
      Macrophage count was computed from the histology of all rat lungs. RESULTS: A
      significant increase in lac/pyr was observed in both right and left lungs of the
      irradiated cohort compared to the healthy cohort for all time points. No increase
      in lac/pyr was observed in the hearts of the irradiated cohort compared to the
      hearts of the healthy cohorts. Blood lactate concentration and paO2 did not show
      a significant change between the irradiated and the healthy cohorts. Macrophage
      count in both right and left lungs was elevated for the irradiated cohort
      compared to the healthy cohort. CONCLUSIONS: Metabolic changes associated with RP
      may be mapped as early as five days post conformal radiotherapy. Over the small
      sample size in each cohort, elevated macrophage count, consistent with early
      phase of inflammation was highly correlated to increases in lac/pyr in both the
      irradiated and unirradiated lungs. Further experiments with larger sample size
      may improve the confidence of this finding.

PMID- 24440042
TI  - Reply to R. Abratt. "Neutron therapy and increased complication rate".

PMID- 24440043
TI  - Dose to the inferior pharyngeal constrictor predicts prolonged gastrostomy tube
      dependence with concurrent intensity-modulated radiation therapy and chemotherapy
      for locally-advanced head and neck cancer.
AB  - BACKGROUND AND PURPOSE: To determine if dose and/or dose-volume parameters to
      anatomic swallowing structures are predictive of gastrostomy tube (PEG)
      dependence from chemotherapy-intensity modulated radiotherapy (IMRT) in locally
      advanced head and neck cancer (LAHNC). METHODS AND MATERIALS: A retrospective
      study was performed on 141 consecutive patients with LAHNC (squamous cell)
      treated with definitive chemoIMRT with weekly concurrent carboplatin and
      paclitaxel. Late dysphagia was assessed by length of PEG requirement. Analysis of
      IMRT dose was retrospectively performed for critical swallowing structures.
      RESULTS: Approximately 62% of patients required PEG, the majority placed during
      treatment. Mean and median time for PEG was 7.7 and 4.4 months respectively
      (range 1.4-43.8). Only IMRT dose to the inferior constrictor was significantly
      associated with length of PEG. Mean dose (of individual mean doses) was 47 Gy for
      prolonged PEG use versus 41 Gy for PEG ? 12 months. V40 to the inferior
      constrictor also correlated with PEG >12 months (p = 0.02) with a mean V40 of 48%
      versus 41% for PEG ? 12 months. CONCLUSIONS: IMRT dose to the inferior
      constrictor correlated with persistent dysphagia requiring prolonged PEG use.
      Maintaining mean inferior constrictor dose to ? 41 Gy and V40 to ? 41% may help
      minimize gastrostomy tube dependence.

PMID- 24440044
TI  - Cross-validation of two commercial methods for volumetric high-resolution dose
      reconstruction on a phantom for non-coplanar VMAT beams.
AB  - BACKGROUND AND PURPOSE: Delta(4) (ScandiDos AB, Uppsala, Sweden) and ArcCHECK
      with 3DVH software (Sun Nuclear Corp., Melbourne, FL, USA) are commercial quasi
      three-dimensional diode dosimetry arrays capable of volumetric measurement-guided
      dose reconstruction. A method to reconstruct dose for non-coplanar VMAT beams
      with 3DVH is described. The Delta(4) 3D dose reconstruction on its own phantom
      for VMAT delivery has not been thoroughly evaluated previously, and we do so by
      comparison with 3DVH. MATERIALS AND METHODS: Reconstructed volumetric doses for
      VMAT plans delivered with different table angles were compared between the
      Delta(4) and 3DVH using gamma analysis. RESULTS: The average gamma (2% local dose
      error normalization/2mm) passing rate comparing the directly measured Delta(4)
      diode dose with 3DVH was 98.2 +/- 1.6% (1SD). The average passing rate for the
      full volumetric comparison of the reconstructed doses on a homogeneous
      cylindrical phantom was 95.6 +/- 1.5%. No dependence on the table angle was
      observed. CONCLUSIONS: Modified 3DVH algorithm is capable of 3D VMAT dose
      reconstruction on an arbitrary volume for the full range of table angles. Our
      comparison results between different dosimeters make a compelling case for the
      use of electronic arrays with high-resolution 3D dose reconstruction as primary
      means of evaluating spatial dose distributions during IMRT/VMAT verification.

PMID- 24440045
TI  - Arc therapy for total body irradiation--a robust novel treatment technique for
      standard treatment rooms.
AB  - BACKGROUND AND PURPOSE: We developed a simple and robust total body irradiation
      (TBI) method for standard treatment rooms that obviates the need for patient
      translation devices. METHODS AND MATERIALS: Two generic arcs with rectangular
      segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An
      analytical fit was performed to determine the weights of the arc segments
      depending on patient thickness and gantry angle. Stability and absolute dose for
      both arcs were measured using EBT3 films in a range of solid water slab phantom
      thicknesses. Additionally ionization chamber measurements were performed every 10
      cm at a source surface distance (SSD) of ~ 200 cm. RESULTS: The measured standard
      deviation for arc16 is +/- 3% with a flatness ? 9.0%. Arc20 had a standard
      deviation of +/- 3% with a flatness ? 7.3% for all measured thicknesses. The
      theoretical curves proved to be accurate for the prediction of the segment
      weightings for the two arcs. In vivo measurements for the first 22 clinical
      patients showed a dose deviation of less than 3%. CONCLUSIONS: Arc therapy is a
      convenient and stable method for TBI. This cost-effective approach has been
      introduced clinically, obviating the need for field patches and to physically
      move the patient.

PMID- 24440046
TI  - Radiolabeled anti-EGFR-antibody improves local tumor control after external beam
      radiotherapy and offers theragnostic potential.
AB  - PURPOSE: The effect of radioimmunotherapy (RIT) using the therapeutic
      radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with
      external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo
      was examined. METHODS: Growth delay was evaluated in three human squamous cell
      carcinoma models after RIT with [(90)Y]Y-(CHX-A''-DTPA)4-cetuximab (Y-90
      cetuximab). The EBRT dose required to cure 50% of the tumors (TCD50) for EBRT
      alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non
      responder (UT-SCC-5). EGFR expression and microenvironmental parameters were
      evaluated in untreated tumors, bioavailability was visualized by PET using
      ([(86)Y]Y-(CHX-A''-DTPA)4-cetuximab (Y-86-cetuximab) and biodistribution using Y
      90-cetuximab. RESULTS: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled
      cetuximab led to significant tumor growth delay. TCD50 after EBRT was
      significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In
      contrast to EGFR expression, parameters of the tumor micromilieu and in
      particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in
      PET correlated with the responsiveness to RIT or EBRIT. CONCLUSION: EGFR-targeted
      EBRIT can improve permanent local tumor control compared to EBRT alone. PET
      imaging of bioavailability of labeled cetuximab appears to be a suitable
      predictor for response to EBRIT. This theragnostic approach should be further
      explored for clinical translation.

PMID- 24440047
TI  - Hypofractionated regional nodal irradiation for breast cancer: examining the data
      and potential for future studies.
AB  - Limited data are available examining the role of hypofractionated radiation
      schedules in the management of women requiring regional nodal irradiation (RNI).
      The purpose of this review is to examine the available literature for the
      efficacy (where available) and toxicity of hypofractionated radiation schedules
      in breast cancer with RNI limited to the axilla and supraclavicular regions.
      Multiple randomized and prospective studies have documented the safety and
      efficacy of hypofractionated schedules delivering whole breast irradiation (WBI)
      alone. Subsets from these randomized trials and smaller prospective/single
      institution studies have documented the feasibility of hypofractionated RNI but
      the limited numbers prevent definitive conclusions and limited efficacy data are
      available. With regard to possible toxicity affecting organs at risk with RNI,
      key structures include the breast, skin, heart, lungs, axilla (lymphedema), and
      brachial plexus. Based on data from several randomized trials, hypofractionated
      radiation is not associated with significant changes in breast toxicity/cosmesis
      or cardiac toxicity; the addition of hypofractionated RNI would not be expected
      to change the rates of breast or cardiac toxicity. While RNI has been shown to
      increase rates of pulmonary toxicity, hypofractionated RNI has not been
      associated with more frequent pulmonary complications than standard RNI. Moving
      forward, future studies will have to evaluate for increased lung toxicity. With
      regard to lymphedema, data from randomized hypofractionated WBI trials failed to
      demonstrate an increase in lymphedema and smaller studies utilizing
      hypofractionated RNI have failed to as well. Data from head and neck cancer as
      well as hypofractionated breast radiation with RNI have failed to demonstrate an
      increase in brachial plexopathy with the exception of older trials that used much
      larger dose per fraction (>4 Gy/fraction) schedules. At this time, published data
      support the feasibility of hypofractionated RNI and the need for a prospective
      randomized trial addressing clinical outcomes and toxicity of hypofractionated
      RNI compared with standard fractionation RNI.

PMID- 24440048
TI  - CD133+ cells contribute to radioresistance via altered regulation of DNA repair
      genes in human lung cancer cells.
AB  - BACKGROUND: Radioresistance in human tumors has been linked in part to a subset
      of cells termed cancer stem cells (CSCs). The prominin 1 (CD133) cell surface
      protein is proposed to be a marker enriching for CSCs. We explore the importance
      of DNA repair in contributing to radioresistance in CD133+ lung cancer cells.
      MATERIALS AND METHODS: A549 and H1299 lung cancer cell lines were used. Sorted
      CD133+ cells were exposed to either single 4 Gy or 8 Gy doses and clonogenic
      survival measured. Upsilon-H2AX immunofluorescence and quantitative real time PCR
      was performed on sorted CD133+ cells both in the absence of IR and after two
      single 4 Gy doses. Lentiviral shRNA was used to silence repair genes. RESULTS:
      A549 but not H1299 cells expand their CD133+ population after single 4 Gy
      exposure, and isolated A549 CD133+ cells demonstrate IR resistance. This
      resistance corresponded with enhanced repair of DNA double strand breaks (DSBs)
      and upregulated expression of DSB repair genes in A549 cells. Prior IR exposure
      of two single 4 Gy doses resulted in acquired DNA repair upregulation and
      improved repair proficiency in both A549 and H1299. Finally Exo1 and Rad51
      silencing in A549 cells abrogated the CD133+ IR expansion phenotype and induced
      IR sensitivity in sorted CD133+ cells. CONCLUSIONS: CD133 identifies a population
      of cells within specific tumor types containing altered expression of DNA repair
      genes that are inducible upon exposure to chemotherapy. This altered gene
      expression contributes to enhanced DSB resolution and the radioresistance
      phenotype of these cells. We also identify DNA repair genes which may serve as
      promising therapeutic targets to confer radiosensitivity to CSCs.

PMID- 24440049
TI  - Prevalence and correlates of alcohol and cannabis use disorders in the United
      States: results from the national longitudinal study of adolescent health.
AB  - BACKGROUND: Limited current information on the epidemiology of lifetime alcohol
      and cannabis use disorders in the United States is available. AIMS: To present
      detailed information about the prevalence and sociodemographic correlates of
      lifetime alcohol and cannabis use disorders rates in the United States. To
      examine gender differences in hazard ratios for the onset of alcohol and cannabis
      dependence. METHODS: Participants in Wave IV of the National Longitudinal Study
      of Adolescent Health (N=15,500, age range: 24-32) were interviewed between 2008
      and 2009. Participants who exceeded screening thresholds were queried about
      lifetime DSM-IV alcohol and marijuana abuse and dependence symptoms. Age of
      substance dependence onset was queried. RESULTS: Lifetime rates of alcohol abuse
      and dependence were 11.8 and 13.2%. Lifetime rates of cannabis abuse and
      dependence were 3.9 and 8.3%. Lifetime alcohol and cannabis dependence onset
      peaks were 23 and 20. Correlates of lifetime alcohol abuse included being male
      (OR 1.4), African-American (OR 0.7), income in the 2nd or 3rd quartile (OR 0.7
      and 0.6). Correlates of lifetime alcohol dependence were: being male (OR 1.8),
      African-American (OR 0.5), and never being married (OR 1.5), and regions outside
      of the west (Midwest OR 0.7, South OR 0.6, Northeast OR 0.6). Correlates of
      cannabis abuse and dependence were being male (OR 1.8 and 1.4). CONCLUSIONS:
      Lifetime alcohol and cannabis use disorders are highly prevalent in the US
      population. Men are at higher risk for alcohol and cannabis use disorders.
      Alcohol use disorders demonstrated specific sociodemographic correlates while
      marijuana use disorders did not.

PMID- 24440050
TI  - Estimating the causal effects of cumulative treatment episodes for adolescents
      using marginal structural models and inverse probability of treatment weighting.
AB  - BACKGROUND: Substance use treatment is rarely a one-time event for individuals
      with substance use disorders. Sustained reductions in substance use and its
      related symptoms may result from multiple treatment episodes. METHODS: We use a
      marginal structural model with inverse-probability-of-treatment weighting to
      estimate the causal effects of cumulative treatment experiences over a period of
      9 months on drug use at the end of 1-year among 2870 adolescents receiving care
      in community-based treatment settings. During the 9 months, adolescents move in
      and out of outpatient and residential treatment with periods where they only
      receive biological drug screening (BDS) or no treatment at all. The use of
      inverse-probability-of-treatment weighting reduces confounding bias due to
      observed baseline and time-varying measures over the course of follow-up; weights
      were estimated using generalized boosted models. RESULTS: Each additional period
      of treatment (representing at least one day, 1 session, or 1 BDS during the 90
      day period between follow-up visits) yielded reductions in average substance use
      frequency at 1-year relative to no treatment during the 90-day period. For
      residential treatment it was a 16% decrease (95% CI=-27%, -7%), for outpatient
      treatment it was a 9% decrease (95% CI=-18%, -0%), and for BDS (with no
      additional outpatient or residential treatment) it was an 11% decrease (95% CI=
      20%, -3%). CONCLUSIONS: Using robust statistical methods, we find promising
      (albeit preliminary) evidence that additional periods of outpatient and
      residential treatment, as well as biological drug screening, lead to reductions
      in substance use outcomes at one year.

PMID- 24440051
TI  - Investigation of sex-dependent effects of cannabis in daily cannabis smokers.
AB  - BACKGROUND: Women exhibit an accelerated progression from first cannabis use to
      cannabis use disorder (CUD) and show pronounced negative clinical issues related
      to CUD relative to men. Whether sex-dependent differences in cannabis' direct
      effects contribute to the heightened risk in women is unknown. This analysis
      directly compared cannabis' abuse-related subjective effects in men and women
      matched for current cannabis use. METHODS: Data from four double-blind, within
      subject studies measuring the effects of active cannabis (3.27-5.50% THC,
      depending on study) relative to inactive cannabis (0.00% THC) were combined for
      this analysis. Data from equal numbers of men and women from each study matched
      for current cannabis use were pooled (total n=35 men; 35 women); cannabis'
      effects were analyzed according to cannabis condition (active versus inactive)
      and sex. RESULTS: Active cannabis produced more robust subjective effects
      associated with abuse liability ('Good,' 'Liking,' 'Take Again') and intoxication
      ('High,' 'Stimulated') relative to inactive cannabis (p<=0.0001). Women reported
      higher ratings of abuse-related effects ['Take Again' and 'Good' (p<=0.05)]
      relative to men under active cannabis conditions but did not differ in ratings of
      intoxication. Active cannabis increased heart rate (p<=0.0001) equally for both
      sexes. CONCLUSIONS: The results from this study suggest that when matched for
      cannabis use, women are more sensitive to the subjective effects related to
      cannabis' abuse liability relative to men, which may contribute to the enhanced
      vulnerability to developing CUD. Thus, sex is an important variable to consider
      when assessing the development of CUD.

PMID- 24440053
TI  - Outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative
      patients.
AB  - PURPOSE: The outcomes and predictors of mortality from Pneumocystis pneumonia
      (PCP) in HIV-negative patients requiring mechanical ventilation (MV) for
      respiratory failure were evaluated. MATERIALS AND METHODS: This retrospective
      observational study enrolled 48 patients with PCP requiring MV in the medical
      intensive care unit (ICU). Multiple logistic regression analysis was used to
      identify independent predictors of in-hospital mortality. RESULTS: The main
      conditions underlying the PCP were malignancies (60%) or post solid organ
      transplant (35%). Excluding four patients whose initial treatment was changed due
      to adverse reactions, 21 (44%) of 44 patients did not respond to the initial
      treatment. During the ICU stay, additional complications developed: shock in 22
      (46%), ventilator-associated pneumonia in 16 (33%), and acute kidney injury in 15
      (31%). Ultimately, 31 (65%) patients died while hospitalised. In multivariate
      analysis, hospital mortality was independently associated with severity of
      illness on ICU admission, failure of initial antimicrobial treatment for PCP, and
      newly developed shock during ICU stay. CONCLUSIONS: PCP in HIV-negative patients
      requiring MV for respiratory failure remains a serious illness with high
      mortality. Failure of the initial antimicrobial treatment for PCP as well as
      severity of illness was independent predictors of poor outcomes.

PMID- 24440052
TI  - New knockout model confirms a role for androgen receptors in regulating anxiety
      like behaviors and HPA response in mice.
AB  - Men are less likely than women to suffer from anxiety disorders. Because gonadal
      hormones play a crucial role in many behavioral sex differences, they may
      underlie sex differences in human anxiety. In rodents, testosterone (T) exerts
      anxiolytic effects via the androgen receptor (AR): we found that male mice with a
      naturally-occurring mutation rendering the AR dysfunctional, referred to as
      spontaneous testicular feminization mutation (sTfm), showed more anxiety-like
      behaviors than wildtype (WT) males. Here, we used Cre-lox recombination
      technology to create another dysfunctional allele for AR. These induced Tfm
      (iTfm) animals also displayed more anxiety-like behaviors than WTs. We further
      found that AR-modulation of these behaviors interacts with circadian phase. When
      tested in the resting phase, iTfms appeared more anxious than WTs in the open
      field, novel object and elevated plus maze tests, but not the light/dark box.
      However, when tested during the active phase (lights off), iTfms showed more
      anxiety-related behavior than WTs in all four tests. Finally, we confirmed a role
      of T acting via AR in regulating HPA axis activity, as WT males with T showed a
      lower baseline and overall corticosterone response, and a faster return to
      baseline following mild stress than did WT males without T or iTfms. These
      findings demonstrate that this recombined AR allele is a valuable model for
      studying androgenic modulation of anxiety, that the anxiolytic effects of AR in
      mice are more prominent in the active phase, and that HPA axis modulation by T is
      AR dependent. 

PMID- 24440054
TI  - Inhibition of death receptor signaling by bacterial gut pathogens.
AB  - Gastrointestinal bacterial pathogens such as enteropathogenic Escherichia coli,
      Salmonella and Shigella control inflammatory and apoptotic signaling in human
      intestinal cells to establish infection, replicate and disseminate to other
      hosts. These pathogens manipulate host cell signaling through the translocation
      of virulence effector proteins directly into the host cell cytoplasm, which then
      target various signaling pathways. Death receptors such as TNFR1, FAS and TRAIL-R
      induce signaling cascades that are crucial to the clearance of pathogens, and as
      such are major targets for inhibition by pathogens. This review focuses on what
      is known about how bacterial gut pathogens inhibit death receptor signaling to
      suppress inflammation and prevent apoptosis. 

PMID- 24440056
TI  - Endpoints in cancer clinical trials.
AB  - Endpoints are measurable clinical and biological findings that are used for the
      development and assessment of treatment options. In the treatment of cancer,
      endpoints can be classified into two categories: "patient-centered clinical
      endpoints" including overall survival (OS) and health-related quality of life
      (QoL), and "tumor-centered clinical endpoints" such as progression-free survival.
      Surrogate endpoints are tumor-centered clinical endpoints that can be used as
      substitutes for patient-centered clinical endpoints, particularly OS. The choice
      of endpoints in oncology trials is a major problem. The published Consolidated
      Standards of Reporting Trials (CONSORT) best-practice guidelines encourage the
      reporting of clearly defined primary and secondary outcome measures. OS is the
      gold standard of endpoints but as increasing numbers of effective salvage
      treatments become available for many types of cancer, much larger numbers of
      patients are included; this requires a longer follow-up period and increases the
      cost of clinical trials. Thus, tumor-centered clinical endpoints that can be
      assessed earlier and used as surrogates for overall survival are increasingly
      studied, but most of them currently lack standardized definitions to enable cross
      comparison of results among different clinical trials and they have not been
      validated as surrogate endpoints. In addition, the variability of their
      definition can strongly impact the trial's conclusions by affecting both
      statistical power and estimation. In this context, QoL constitutes an available
      and useful surrogate endpoint for trials to ensure treatment benefit from both
      the patient and public health points of view. Methodological research should be
      pursued to develop standard outcome definitions for use in cancer clinical trials
      and to define a standardized longitudinal analysis of QoL data. 

PMID- 24440055
TI  - Synergistic effects of amyloid-beta and wild-type human tau on dendritic spine
      loss in a floxed double transgenic model of Alzheimer's disease.
AB  - Synapse number is the best indicator of cognitive impairment In Alzheimer's
      disease (AD), yet the respective contributions of Abeta and tau, particularly
      human wild-type tau, to synapse loss remain undefined. Here, we sought to
      elucidate the Abeta-dependent changes in wild-type human tau that trigger synapse
      loss and cognitive decline in AD by generating two novel transgenic mouse models.
      The first overexpresses floxed human APP with Swedish and London mutations under
      the thy1 promoter, and recapitulates important features of early AD, including
      accumulation of soluble Abeta and oligomers, but no plaque formation. Transgene
      excision via Cre-recombinase reverses cognitive decline, even at 18-months of
      age. Secondly, we generated a human wild-type tau-overexpressing mouse. Crossing
      of the two animals accelerates cognitive impairment, causes enhanced accumulation
      and aggregation of tau, and results in reduction of dendritic spines compared to
      single transgenic hTau or hAPP mice. These results suggest that Abeta-dependent
      acceleration of wild-type human tau pathology is a critical component of the
      lasting changes to dendritic spines and cognitive impairment found in AD. 

PMID- 24440057
TI  - Surgical approaches to fecal incontinence in the adult.
AB  - Surgical treatment of anal incontinence is indicated only for patients who have
      failed medical treatment. Sphincterorraphy is suitable in case of external
      sphincter rupture. In the last decade, sacral nerve stimulation has proven to be
      a scientifically validated solution when no sphincter lesion has been identified
      and more recently has also been proposed as an alternative in cases of limited
      sphincter defect. Anal reconstruction using artificial sphincters is still under
      evaluation in the literature, while indications for dynamic graciloplasty are
      decreasing due to its complexity and high morbidity. Less risky techniques
      involving intra-sphincteric injections are being developed, with encouraging
      preliminary results that need to be confirmed especially in the medium- and long
      term. Antegrade colonic enemas instilled via cecostomy (Malone) can be an
      alternative to permanent stoma in patients who are well instructed in the
      techniques of colonic lavage. Stomal diversion is a solution of last resort. 

PMID- 24440058
TI  - Influence of consonant voicing characteristics on sentence production in abductor
      versus adductor spasmodic dysphonia.
AB  - OBJECTIVES/HYPOTHESIS: This study evaluated the hypotheses that sentence
      production by speakers with adductor (AD) and abductor (AB) spasmodic dysphonia
      (SD) may be differentially influenced by consonant voicing and manner features,
      in comparison with healthy, matched, nondysphonic controls. STUDY DESIGN: This
      was a prospective, single blind study, using a between-groups, repeated measures
      design for the independent variables of perceived voice quality and sentence
      duration. METHODS: Sixteen subjects with ADSD and 10 subjects with ABSD, as well
      as 26 matched healthy controls produced four short, simple sentences that were
      systematically loaded with voiced or voiceless consonants of either obstruant or
      continuant manner categories. Experienced voice clinicians, who were "blind" as
      to speakers' group affixations, used visual analog scaling to judge the overall
      voice quality of each sentence. Acoustic sentence durations were also measured.
      RESULTS: Speakers with ABSD or ADSD demonstrated significantly poorer than normal
      voice quality on all sentences. Speakers with ABSD exhibited longer than normal
      duration for voiceless consonant sentences. Speakers with ADSD had poorer voice
      quality for voiced than for voiceless consonant sentences. Speakers with ABSD had
      longer durations for voiceless than for voiced consonant sentences. CONCLUSIONS:
      The two subtypes of SD exhibit differential performance on the basis of consonant
      voicing in short, simple sentences; however, each subgroup manifested voicing
      related differences on a different variable (voice quality vs sentence duration).
      Findings suggest different underlying pathophysiological mechanisms for ABSD and
      ADSD. Findings also support inclusion of short, simple sentences containing
      voiced or voiceless consonants as part of the diagnostic protocol for SD, with
      measurement of sentence duration in addition to judments of voice quality
      severity.

PMID- 24440059
TI  - Penetration of cutting tool into cortical bone: experimental and numerical
      investigation of anisotropic mechanical behaviour.
AB  - An anisotropic mechanical behaviour of cortical bone and its intrinsic
      hierarchical microstructure act as protective mechanisms to prevent catastrophic
      failure due to natural loading conditions; however, they increase the extent of
      complexity of a penetration process in the case of orthopaedic surgery.
      Experimental results available in literature provide only limited information
      about processes in the vicinity of a tool-bone interaction zone. Also, available
      numerical models the bone-cutting process do not account for material anisotropy
      or the effect of damage mechanisms. In this study, both experimental and
      numerical studies were conducted to address these issues and to elucidate the
      effect of anisotropic mechanical behaviour of cortical bone tissue on penetration
      of a sharp cutting tool. First, a set of tool-penetration experiments was
      performed in directions parallel and perpendicular to bone axis. Also, these
      experiments included bone samples cut from four different cortices to evaluate
      the effect of spatial variability and material anisotropy on the penetration
      processes. Distinct deformation and damage mechanisms linked to different
      microstructure orientations were captured using a micro-lens high-speed camera.
      Then, a novel hybrid FE model employing a smoothed-particle-hydrodynamic domain
      embedded into a continuum FE one was developed based on the experimental
      configuration to characterise the anisotropic deformation and damage behaviour of
      cortical bone under a penetration process. The results of our study revealed a
      clear anisotropic material behaviour of the studied cortical bone tissue and the
      influence of the underlying microstructure. The proposed FE model reflected
      adequately the experimental results and demonstrated the need for the use of the
      anisotropic and damage material model to analyse cutting of the cortical-bone
      tissue. 

PMID- 24440060
TI  - Introduction.

PMID- 24440061
TI  - Effect of frequency on subthalamic nucleus deep brain stimulation in primary
      dystonia.
AB  - BACKGROUND: Subthalamic nucleus deep brain stimulation (DBS) is an alternative
      target choice for treating primary dystonia, but little is known about the most
      effective programming parameters. OBJECTIVE: Here we prospectively evaluate the
      effect of low versus high frequency subthalamic nucleus DBS in patients with
      predominantly cervical or upper extremity primary dystonia. METHODS: Seven
      patients were stimulated at low frequency stimulation (60 Hz) for the first three
      months and then switched to high frequency stimulation (130 Hz) until month six.
      Severity of dystonia was determined by a blinded rater (unaware of the patient's
      pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating
      scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis
      Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve
      months post-surgery. RESULTS: Patients had a lower mean improvement of 16.6% in
      BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation
      compared to a 52.3% (p = 0.018) and 45.2% (p = 0.028), respectively, noted at six
      months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS
      M and TWSTRS-S improved by 51.8% (p = 0.022) and 56% (p = 0.034). Patients
      developed transient dyskinesia (during low and high frequency stimulation) which
      improved with programming adjustments. CONCLUSION: This study offers further
      support of the effectiveness of subthalamic nucleus DBS in the treatment of
      primary dystonia and finds that high frequency stimulation was more effective
      than low frequency stimulation.

PMID- 24440062
TI  - Operative vs nonoperative management for blunt pancreatic transection in
      children: multi-institutional outcomes.
AB  - BACKGROUND: The management of traumatic pancreatic transection remains
      controversial. STUDY DESIGN: A multi-institutional review from 1995 to 2012 was
      conducted comparing operative with nonoperative management for grades II and III
      blunt pancreatic injuries in patients younger than 18 years. RESULTS: Fourteen
      pediatric trauma centers participated, yielding 167 patients; 57 underwent distal
      pancreatectomy and 95 were managed nonoperatively. Fifteen patients treated with
      operative drain placement only were studied separately. Patients undergoing
      resection had a shorter time to goal oral feeds (7.8 +/- 0.7 days vs 15.1 +/- 2.5
      days; p = 0.007) and a lower rate of pseudocyst formation (0% vs 18%; p = 0.001).
      Pseudocyst formation resulted in a greater need for endoscopic and interventional
      radiologic procedures (26% vs 2%; p = 0.002) in the nonoperative group, as well
      as a longer time to complete resolution (38.6 +/- 6.4 days vs 22.6 +/- 5.0 days;
      p = 0.05) compared with resection. When looking at those patients with clear
      evidence of main duct injury at presentation, those undergoing resection also had
      fewer complications (33% vs 61%; p = 0.05) and fewer total days in-hospital (12.6
      +/- 8.4 days vs 17.5 +/- 9.7 days; p = 0.04) compared with nonoperative
      management. CONCLUSIONS: In children with blunt pancreatic injury, distal
      pancreatectomy is superior to nonoperative management with more rapid resumption
      of diet, fewer repeat interventions, and a shorter period to complete resolution.
      When the main duct is involved, the benefits to operative resection also include
      lower morbidity and fewer days of hospitalization. Therefore, assessing the
      status of the pancreatic duct is paramount in determining management.

PMID- 24440064
TI  - A simple effective method for generation of a permanent record of the Critical
      View of Safety during laparoscopic cholecystectomy by intraoperative "doublet"
      photography.
AB  - BACKGROUND: The Critical View of Safety (CVS) is an established method for
      identifying the cystic duct during laparoscopic cholecystectomy. Its goal is to
      prevent misidentification of the bile ducts and avoid biliary injury. However, a
      visual record of CVS is not usually made. Intraoperative photography has the
      potential to record CVS and increase the safety of laparoscopic cholecystectomy.
      The objective of this study was to develop a simple and effective technique for
      recording CVS during laparoscopic cholecystectomy. STUDY DESIGN: Techniques for
      photographing and rating photographs of CVS were developed. Surgeons were trained
      in methods of photographing both anterior and posterior views of CVS during
      laparoscopic cholecystectomy. Independent observers scored these views
      individually and together. The term doublet view was used when both anterior and
      posterior views of CVS were used for rating. Three criteria for CVS were used for
      scoring photographs. A total score of >= 5 of 6 points was considered
      satisfactory, and a total score <5 of 6 points was considered unsatisfactory.
      RESULTS: Photographs of 28 patients were obtained. Critical View of Safety
      photographs were satisfactory in either anterior or posterior single images in 43
      of 56 (76.8%) instances, and doublet photographs were satisfactory in 27 of 28
      (96.4%) instances (p = 0.02). Body mass index >40 predicted a higher likelihood
      of unsatisfactory individual CVS photos (p = 0.02); however, there was no
      correlation between patient or pathologic factors and the scores of doublet
      views. CONCLUSIONS: With training and adherence to straightforward photographic
      techniques, intraoperative doublet photography can record CVS accurately. This
      method is performed easily, and could be used for recording of CVS in the medical
      record.

PMID- 24440063
TI  - Assessment of tumor growth in pancreatic neuroendocrine tumors in von Hippel
      Lindau syndrome.
AB  - BACKGROUND: The incidence of pancreatic neuroendocrine tumors (PNETs) is
      increasing, but only a subset of these heterogeneous tumors will progress to
      malignant disease, which is associated with a poor prognosis. Currently, there
      are limited data on the natural history of these tumors and it is difficult to
      determine which patients require surgical intervention because the risk of
      metastatic disease cannot be accurately determined. STUDY DESIGN: We conducted a
      prospective study of 87 patients with von Hippel Lindau syndrome-associated solid
      pancreatic lesions to determine the natural history of these tumors with
      biochemical testing, follow-up anatomic and functional imaging, and advanced
      imaging analysis, with a median follow-up of 4 years. RESULTS: Approximately 20%
      of consecutive tumor measurements during follow-up were decreased in size and 20%
      showed no change. This included 2 of 4 surgically proven malignant tumors, which
      had a net decrease in tumor size over time. Tumor volume, as derived from
      greatest diameter and volumetric measurements, showed good correlation to
      pathology tumor measurement of surgically resected tumors (Spearman rank
      correlation rho = 0.72, p = 0.0011, and rho = 0.83, p < 0.0001, respectively).
      Tumor density measurement had an inverse relationship with tumor size (Spearman
      rank correlation -0.22, p = 0.0047). A tumor density cutoff of 200 was 75%
      specific for malignant tumors. CONCLUSIONS: Pancreatic neuroendocrine tumors
      demonstrate a nonlinear growth pattern, which includes periods of no growth and
      apparent decrease in size by imaging. These growth patterns are variable and are
      not associated with tumor grade and malignancy. Tumor density, as measured in
      this cohort, may offer a specific diagnostic tool for malignant disease.

PMID- 24440065
TI  - Derivation and validation of a simple calculator to predict home discharge after
      surgery.
AB  - BACKGROUND: Surgical patients and their physicians currently have tools to
      provide individualized prognostication for morbidity and mortality. For improved
      shared decision making, formal prediction of patient-centered outcomes is
      necessary. We derived and validated a simple, interview-based method to predict
      discharge home after surgery. STUDY DESIGN: We used the American College of
      Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Patient User
      File for 2011. Derivation in general and vascular surgery patients undergoing
      inpatient surgery was completed using serial multiple logistic regression.
      Validation was performed within multiple surgical specialties. RESULTS: The
      derivation cohort included 88,068 patients, of whom 11,771 (13.4%) were not
      discharged home. The derived Home Calculator had excellent discrimination (c
      statistic = 0.864) using 5 [corrected] variables: age, American Society of
      Anesthesiologists' performance status, elective surgery, and preadmission
      residence. Validation cohorts had varying rates of home discharge as follows:
      general (63,826 of 71,591, 89.2%), vascular (12,319 of 16,102, 76.5%),
      gynecologic (16,603 of 17,005, 97.6%), urologic (13,662 of 14,435, 94.6%),
      orthopaedic (12,000 of 19,514, 61.5%), thoracic (4,467 of 5,092, 87.7%). The Home
      Calculator provided good to excellent discrimination in validation cohorts:
      general (c = 0.866), vascular (c = 0.800), gynecologic (c = 0.793), urologic (c =
      0.814), orthopaedic (c = 0.876), and thoracic (c = 0.800). Comparable
      discrimination was demonstrated in sensitivity analyses in surgical patients
      admitted exclusively from home. CONCLUSIONS: We derived and validated a simple
      Home Calculator that reliably predicts discharge to home after surgery and may be
      useful when counseling patients about postoperative course. Patient-centered
      tools such as this may allow physicians to better prepare patients and families
      for surgery and the recovery process.

PMID- 24440067
TI  - Classification techniques in analyzing surgical outcomes data.

PMID- 24440068
TI  - Raymond Joehl's Presidential Address regarding the Veteran's Administration.

PMID- 24440066
TI  - Comparison of prospective risk estimates for postoperative complications: human
      vs computer model.
AB  - BACKGROUND: Surgical quality improvement tools such as NSQIP are limited in their
      ability to prospectively affect individual patient care by the retrospective
      audit and feedback nature of their design. We hypothesized that statistical
      models using patient preoperative characteristics could prospectively provide
      risk estimates of postoperative adverse events comparable to risk estimates
      provided by experienced surgeons, and could be useful for stratifying
      preoperative assessment of patient risk. STUDY DESIGN: This was a prospective
      observational cohort. Using previously developed models for 30-day postoperative
      mortality, overall morbidity, cardiac, thromboembolic, pulmonary, renal, and
      surgical site infection (SSI) complications, model and surgeon estimates of risk
      were compared with each other and with actual 30-day outcomes. RESULTS: The study
      cohort included 1,791 general surgery patients operated on between June 2010 and
      January 2012. Observed outcomes were mortality (0.2%), overall morbidity (8.2%),
      and pulmonary (1.3%), cardiac (0.3%), thromboembolism (0.2%), renal (0.4%), and
      SSI (3.8%) complications. Model and surgeon risk estimates showed significant
      correlation (p < 0.0001) for each outcome category. When surgeons perceived
      patient risk for overall morbidity to be low, the model-predicted risk and
      observed morbidity rates were 2.8% and 4.1%, respectively, compared with 10% and
      18% in perceived high risk patients. Patients in the highest quartile of model
      predicted risk accounted for 75% of observed mortality and 52% of morbidity.
      CONCLUSIONS: Across a broad range of general surgical operations, we confirmed
      that the model risk estimates are in fairly good agreement with risk estimates of
      experienced surgeons. Using these models prospectively can identify patients at
      high risk for morbidity and mortality, who could then be targeted for
      intervention to reduce postoperative complications.

PMID- 24440069
TI  - Necrotizing soft tissue infections.

PMID- 24440070
TI  - Reply: To PMID 23628224.

PMID- 24440071
TI  - Liver transplantation for cholangiocarcinoma beyond a clinical trial.

PMID- 24440072
TI  - Reply: To PMID 23890842.

PMID- 24440073
TI  - Mesocaval shunting.

PMID- 24440074
TI  - Reply: To PMID 23816382.

PMID- 24440075
TI  - Cross-leg flaps: preferred alternative to free flaps?

PMID- 24440076
TI  - Reply: To PMID 23890841.

PMID- 24440078
TI  - Detection of miRNA expression in intact cells using activatable sensor
      oligonucleotides.
AB  - We describe a technology for the profiling of miRNA expression in intact cells.
      The technology is based on sensor oligonucleotides that are cleavable, completely
      complementary to a target miRNA, and dual-labeled with a fluorescent dye and a
      quencher. Upon entering the cell, the sensor oligonucleotide binds its specific
      miRNA target through complementary base-pairing. This triggers assembly of the
      endogenous RNA Induced Silencing Complex (RISC) around the miRNA-sensor duplex
      and cleavage of the sensor oligonucleotide, resulting in separation between the
      dye and quencher, and a fluorescence turn-on. In the presented feasibility
      studies, we focus on a specific miRNA (miR-10b) implicated in breast cancer
      metastasis. Using a human breast adenocarcinoma cell line, we illustrate the
      application of this technology for miRNA detection with nanomolar sensitivity in
      both a cell-free system and intact cells.

PMID- 24440079
TI  - Design and synthesis of truncated EGF-A peptides that restore LDL-R recycling in
      the presence of PCSK9 in vitro.
AB  - Disrupting the binding interaction between proprotein convertase (PCSK9) and the
      epidermal growth factor-like domain A (EGF-A domain) in the low-density
      lipoprotein receptor (LDL-R) is a promising strategy to promote LDL-R recycling
      and thereby lower circulating cholesterol levels. In this study, truncated 26
      amino acid EGF-A analogs were designed and synthesized, and their structures were
      analyzed in solution and in complex with PCSK9. The most potent peptide had an
      increased binding affinity for PCSK9 (KD = 0.6 MUM) compared with wild-type EGF-A
      (KD = 1.2 MUM), and the ability to increase LDL-R recycling in the presence of
      PCSK9 in a cell-based assay.

PMID- 24440080
TI  - Prevention of cell death by antibodies selected from intracellular combinatorial
      libraries.
AB  - One of the most important phenotypes in biology is cell death. One way to probe
      the mechanism(s) of cell death is to select molecules that prevent it and learn
      how this was accomplished. Here, intracellular combinatorial antibody libraries
      were used to select antibodies that protected cells from killing by rhinovirus
      infection. These rare antibodies functioned by inhibiting the virus-encoded
      protease that is necessary for viral maturation. Snapshots of the selection
      process after each round could be obtained by deep sequencing the ever-enriching
      populations. This detailed analysis of the enrichment process allowed an
      interesting look at a "test tube" selection process that pitted two replicating
      systems against each other. Thus, initially a minority of cells containing
      protective antibodies must compete against a majority of unprotected cells that
      continue to produce large amounts of virus.

PMID- 24440081
TI  - A PEF/Y substrate recognition and signature motif plays a critical role in DAPK
      related kinase activity.
AB  - Knowledge about protein kinase substrate preferences is biased toward residues
      immediately adjacent to the site of phosphorylation. By a combined structural,
      biochemical, and cellular approach, we have discovered an unexpected substrate
      recognition element with the consensus sequence PEF/Y in the tumor suppressor
      death-associated protein kinase 1. This motif can be effectively blocked by a
      specific pseudosubstrate-type interaction with an autoregulatory domain of this
      kinase. In this arrangement, the central PEF/Y glutamate interacts with a
      conserved arginine distant to the phosphorylation site in sequence and structure.
      We also demonstrate that the element is crucial for kinase activity regulation
      and substrate recognition. The PEF/Y motif distinguishes close death-associated
      protein kinase relatives from canonical calcium/calmodulin-dependent protein
      kinases. Insight into this signature and mode of action offers new opportunities
      to identify specific small molecule inhibitors in PEF/Y-containing protein
      kinases. 

PMID- 24440082
TI  - Elucidating the adaptation and temporal coordination of metabolic pathways using
      in-silico evolution.
AB  - Cellular metabolism, the interconversion of small molecules by chemical
      reactions, is a tightly coordinated process that requires integration of diverse
      environmental and intracellular cues. While for many organisms the topology of
      the network of metabolic reactions is increasingly known, the regulatory
      principles that shape the network's adaptation to diverse and changing
      environments remain largely elusive. To investigate the principles of metabolic
      adaptation and regulation in metabolic pathways, we propose a computational
      approach based on in-silico evolution. Rather than analyzing existing regulatory
      schemes, we let a population of minimal, prototypical metabolic cells evolve rate
      constants and appropriate regulatory schemes that allow for optimal growth in
      static and fluctuating environments. Applying our approach to a small, but
      already sufficiently complex, minimal system reveals intricate transitions
      between metabolic modes. These results have implications for trade-offs in
      resource allocation. Going from static to varying environments, we show that for
      fluctuating nutrient availability, active metabolic regulation results in a
      significantly increased overall rate of metabolism. 

PMID- 24440083
TI  - Pre-operative training induces changes in the histomorphometry and muscle
      function of the pelvic floor in patients with indication of radical
      prostatectomy.
AB  - OBJECTIVE: To evaluate the efficacy of preoperative pelvic floor muscle training
      (PFMT) on histomorphometry, muscle function, urinary continence and quality of
      life of patients undergoing radical prostatectomy (RP). MATERIAL AND METHODS: A
      prospective intervention clinical study was designed in 16 patients with
      indication of RP who were randomized into two groups. The Control Group received
      routine pre-surgical education (hygienic-dietary measures). The intervention
      group received a training session with supervised PFMT, three times a day, for
      four weeks, 30 days before the PR. Muscle function of the external urethral
      sphincter, contraction pressure of the levator ani, urinary continence and
      quality of life related to health (HRQoL) were evaluated before and after the
      intervention. At the end of the intervention and day of the surgery, samples of
      residual muscle tissue were obtained from the external sphincter muscle of the
      urethra for histomorphometric analysis. RESULTS: After the intervention, those
      participants who carried out PFMT showed an increase in the cross-sectional area
      of the muscle fibers of the external urethral sphincter (1,313 +/- 1,075
      MUm(2)vs. 1,056 +/- 844 MUm(2), P=.03) and higher pressure contraction of the
      levator ani (F=9.188; P=.010). After catheter removal, 62% of patients in the
      experimental group and 37% in the control group showed no incontinence. After
      removal of the catheter, 75% of the experimental group did not require any pad
      compared to 25% in the control group (p=NS). There were no significant
      differences between the two groups in any of the HRQoL domains studied.
      CONCLUSIONS: Pre-surgical PFMT in patients with RP indication induces changes in
      the histology and function of the pelvic floor muscles, without changes in
      urogenital function and HRQoL. These results provide new evidence regarding the
      benefit of PFMT in preventing RP associated complications.

PMID- 24440084
TI  - The relationship between secondary hyperparathyroidism and thyroid cancer in end
      stage renal disease: a population based cohort study.
AB  - OBJECTIVES: We conducted a retrospective cohort study to investigate the risk of
      cancer in end stage renal disease (ESRD) patients with secondary
      hyperparathyroidism (HPT). PATIENTS AND METHODS: This study investigated the
      elevated overall cancer risk in ESRD patients with secondary HPT in Taiwan. We
      used a population-based retrospective cohort consisting of original claims data
      of 1 million beneficiaries randomly sampled from the Taiwan National Health
      Insurance Research Database (NHIRD). We calculated the hazard ratios (HRs) and
      95% confidence intervals (CIs) of cancer in the ESRD with secondary HPT and
      comparison cohorts, using the Cox proportional hazards regression model. RESULTS:
      We observed that ESRD patients with secondary HPT exhibited a 10.1-fold increased
      risk of thyroid cancer than did ESRD patients without this parathyroid
      complication, after adjusting for comorbidities (95% confidence interval=1.12
      91.0). CONCLUSION: These phenomena indicate that ESRD patients with secondary HPT
      are at greater risk of thyroid cancer. Physicians should be alert for occult
      thyroid cancer in ESRD patients with secondary HPT.

PMID- 24440085
TI  - A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients
      with advanced solid tumours.
AB  - BACKGROUND: LY2584702 tosylate (hereafter referred to as LY2584702) is a potent,
      highly selective adenosine triphosphate (ATP) competitive inhibitor against p70
      S6 kinase, a downstream component of the phosphatidylinositol-3-kinase signalling
      pathway which regulates cell proliferation and survival. LY2584702 exhibited anti
      tumour activity in preclinical analysis. METHODS: Patients with advanced solid
      tumours were treated with LY2584702 orally on a 28-day cycle until the criteria
      for maximum tolerated dose (MTD) were met. Skin biopsies were collected for
      pharmacodynamic analysis, and levels of phospho-S6 protein were examined. The
      primary objective was to determine a phase II dose and schedule with secondary
      objectives of observing safety and tolerability. Dose escalation was based upon
      Common Terminology Criteria for Adverse Events Version 3.0. RESULTS: Thirty-four
      patients were enrolled onto this phase I study and treated with LY2584702 on a QD
      (once-daily) or BID (twice-daily) dosing schedule. Part A dose escalation (n=22)
      began with 300 mg BID (n=2). Due to toxicity, this was scaled back to doses of
      25mg (n=3), 50 mg (n=8), 100mg (n=3), and 200 mg (n=6) QD. Part B dose escalation
      (n=12) included 50 mg (n=3), 75 mg (n=3), and 100 mg (n=6) BID. Seven patients
      experienced dose-limiting toxicity (DLT). All DLTs were Grade 3 and included
      vomiting, increased lipase, nausea, hypophosphataemia, fatigue and pancreatitis.
      CONCLUSION: The MTD was determined to be 75 mg BID or 100mg QD. No responses were
      observed at these levels. Pharmacokinetic analysis revealed substantial
      variability in exposure and determined that LY2584702 treatment was not dose
      proportional with increasing dose.

PMID- 24440086
TI  - Magnetic resonance imaging defined mucinous rectal carcinoma is an independent
      imaging biomarker for poor prognosis and poor response to preoperative
      chemoradiotherapy.
AB  - INTRODUCTION: Mucinous adenocarcinomas represent a potentially poor prognostic
      subgroup identifiable by imaging. We compared outcomes between magnetic resonance
      imaging (MRI) detected rectal mucinous carcinoma and adenocarcinomas. The
      diagnostic performance of MRI compared with initial biopsy in detecting mucinous
      adenocarcinoma was also assessed. METHODS: The proportion of patients downstaged
      in the mrMucinous and adenocarcinoma groups was compared. Cox proportional hazard
      models were used to test independence of mucinous status and baseline MRI and
      clinical variables on survival. Differences in survival for mucinous versus non
      mucinous tumours were tested for significance using the Mantel-Cox log rank test.
      RESULTS: 60/330 (18%) patients were correctly diagnosed with mucinous rectal
      cancer based on pre treatment MRI compared with 15/330 (5%) on initial biopsy
      (diagnostic odds ratio=4.67, p<0.05). All 60 (100%) patients undergoing surgery
      for mrMucinous tumours were confirmed as such on final histopathology.
      Significantly fewer mrMucinous tumours showed ypT downstaging when compared with
      non-mucinous tumours (14/60 (23%) versus 111/270 (40%), p=0.01). Three-year
      survival outcomes for patients for MRI detected mucinous tumours were
      significantly worse: disease free survival (DFS) was 48% versus 71%, p=0.006 and
      OS was 69% versus 79% p=0.04. MRI Mucin was an independent variable for poor DFS
      (hazard ratios (HR)) 0.58 95% Confidence interval (CI) 0.38-0.89). CONCLUSIONS:
      MRI diagnosis of mucinous adenocarcinoma is diagnostically superior to
      preoperative biopsy and occurs in up to 20% of rectal cancer patients. It is an
      independent imaging biomarker for response to preoperative chemoradiotherapy
      (CRT) and prognosis. MRI documentation of mucinous status will enable future
      pursuit of treatment strategies in this poor prognostic subgroup.

PMID- 24440087
TI  - Genetic and clinical determinants of constitutional mismatch repair deficiency
      syndrome: report from the constitutional mismatch repair deficiency consortium.
AB  - BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a devastating
      cancer predisposition syndrome for which data regarding clinical manifestations,
      molecular screening tools and management are limited. METHODS: We established an
      international CMMRD consortium and collected comprehensive clinical and genetic
      data. Molecular diagnosis of tumour and germline biospecimens was performed. A
      surveillance protocol was developed and implemented. RESULTS: Overall, 22/23
      (96%) of children with CMMRD developed 40 different tumours. While childhood
      CMMRD related tumours were observed in all families, Lynch related tumours in
      adults were observed in only 2/14 families (p=0.0007). All children with CMMRD
      had cafe-au-lait spots and 11/14 came from consanguineous families. Brain tumours
      were the most common cancers reported (48%) followed by gastrointestinal (32%)
      and haematological malignancies (15%). Importantly, 12 (30%) of these were low
      grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and
      specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene
      while microsatellite instability was neither sensitive nor specific as a
      diagnostic tool (p<0.0001). Furthermore, screening of normal tissue by
      immunohistochemistry correlated with genetic confirmation of CMMRD. The
      surveillance protocol detected 39 lesions which included asymptomatic malignant
      gliomas and gastrointestinal carcinomas. All tumours were amenable to complete
      resection and all patients undergoing surveillance are alive. DISCUSSION: CMMRD
      is a highly penetrant syndrome where family history of cancer may not be
      contributory. Screening tumours and normal tissues using immunohistochemistry for
      abnormal expression of MMR gene products may help in diagnosis and early
      implementation of surveillance for these children.

PMID- 24440088
TI  - Management and treatment results in patients with acute promyelocytic leukaemia
      (APL) not enrolled in clinical trials.
AB  - PURPOSE: Acute promyelocytic leukaemia (APL) therapy with all-trans retinoic acid
      and chemotherapy is associated with a high cure rate in clinical trials. As some
      patients are not enrolled in these trials due to early severe events, these
      results might be overestimated. To address this issue, we reviewed all APL
      patients referred to the Hospital Saint-Louis within the 2000-2010 period, with a
      special focus on inclusion in recruiting trials. PATIENTS AND METHODS: One
      hundred patients (including eight children) with newly diagnosed APL were
      admitted during this period, which covered two consecutive APL trials conducted
      by the French-Belgian-Swiss APL group. RESULTS: The rate of patients not enrolled
      within recruiting trials was 29%. The main reason for non-inclusion was protocol
      ineligibility related to disease severity at diagnosis. Non-enrolled patients
      more frequently had white blood cell count (WBC) . or =50*10(9)/L (31% versus 8%;
      p=.01), platelet count<40*10(9)/L (97% versus 65%; p=.001) and microgranular
      variant APL (38% versus 11%; p=.004) and were more frequently admitted in
      intensive care unit during induction (41% versus 24%; p=.094). Early mortality
      rate was higher in non-enrolled patients (21% versus 3%; p=.007), translating
      into a lower complete remission rate (79% versus 96%; p=.007) and lower event
      free survival (65% versus 84% at 5 years; p=.05), while disease-free survival was
      similar in both non-enrolled and enrolled patient groups (81% versus 88% at 5
      years; p=.68). CONCLUSION: Initial APL severity leads to a significant proportion
      of patients non-registered within clinical trials, which may underestimate the
      real early mortality, which remained nonetheless less than 10% in this study.

PMID- 24440089
TI  - Initial metastatic kinetics is the best prognostic indicator in stage IV
      metastatic melanoma.
AB  - AIM: In metastatic melanoma (MM) there is an agreement that a fast or slow
      progression should influence the choice between drugs with immediate impact (BRAF
      inh) or delayed (ipilimumab) activity. MM kinetics thus appears crucial for
      medical decision, although only estimated through surrogate markers (tumour load
      or lactate dehydrogenase (LDH)). Our objective was to show that 1-MM kinetics can
      be measured and 2- is a real prognostic factor. METHOD: Among all stage IV MM, we
      retrospectively select those with long follow-up who had two comparable total
      body computed tomography (CT) scans within the first 3 months, and did not
      receive meantime any treatment with a likely impact on MM kinetics. Kinetics
      index (KI) was calculated from changes in total metastatic volume
      (DeltaTMV/DeltaT). RESULTS: In 126 patients, KI of progression ranges from 0 to
      24,839 mm3/day. Overall survival (OS) was significantly much lower in the higher
      terciles of KI than in the lower ones (median OS of 459, 388 and 183 days, for KI
      of 0-99, 100-999 and > or =1000 mm3/day, respectively). In the multivariate
      analysis, KI was more predictive of OS than LDH or tumour load. CONCLUSION:
      Delaying major treatments in stage IV MM for a few weeks permits a measure of KI,
      which is the best prognostic indicator in MM. The huge range of KI probably
      reflects major differences in aggressiveness that any therapeutic decision should
      take into account. KI could be used to assess prospectively how much the efficacy
      of each new MM drugs is influenced by MM initial kinetics.

PMID- 24440090
TI  - Mouse models for dengue vaccines and antivirals.
AB  - Dengue virus (DENV) has substantial global impact, with an estimated 390million
      people infected each year. In spite of this, there is currently no approved DENV
      specific vaccine or antiviral. One reason for this is the difficulty involved
      with development of an adequate animal model. While non-human primates support
      viral replication, they do not exhibit signs of clinical disease. A mouse model
      is an ideal alternative; however, wild-type mice are resistant to DENV-induced
      disease. Infection of interferon receptor-deficient mice results in disease that
      recapitulates key features of severe dengue disease in humans. For the
      development of vaccines, interferon receptor-deficient mice provide a stringent
      model for testing vaccine-induced immune components from vaccinated wild-type
      mice. 

PMID- 24440091
TI  - Diabetes complications and adverse health outcomes after coronary
      revascularization.
AB  - AIMS: To examine effects of diabetes complications on health outcomes following
      coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI),
      comparing outcomes for patients with diabetes complications to those without
      diabetes complications. METHODS: Retrospective analysis of discharge data for
      61,566 patients with diabetes age 45 or older who had CABG or PCI in 2007 in
      United States community hospitals, using data from the Nationwide Inpatient
      Sample. Analysis included propensity score-adjusted logistic regression. RESULTS:
      Of all patients, 21.2% of the weighted sample had diabetes complications. Older
      patients, Blacks and Hispanics, and those with greater illness severity were more
      likely to have diabetes complications. Unadjusted rates of in-hospital mortality,
      postoperative stroke, and renal failure were higher for patients with diabetes
      complications (rate ratios 2.2, 1.8, and 9.8, respectively; all p<0.0001). In
      adjusted results, having diabetes complications was associated with higher odds
      of in-hospital mortality (odds ratio, OR 1.62, 95% confidence interval, CI 1.37
      1.91) and renal failure (OR 3.03, CI 1.71-5.39). Compared to CABG, PCI was
      associated with extra risk of postoperative renal failure for those with diabetes
      complications. CONCLUSION: Among patients with diabetes having revascularization,
      those with diabetes complications have higher risks of in-hospital death and
      renal failure irrespective of having CABG or PCI.

PMID- 24440092
TI  - Hypermethylation of the CDKN2A gene promoter is a frequent epigenetic change in
      periocular sebaceous carcinoma and is associated with younger patient age.
AB  - Periocular sebaceous carcinoma is an aggressive neoplasm with significant
      morbidity and mortality. Its pathogenesis is poorly understood. It is only rarely
      associated with Muir-Torre syndrome. Previous studies from Asian countries, have
      suggested that human papillomavirus (HPV) infection plays a role in the
      pathogenesis and overexpression of p16(INK4a), a surrogate marker of HPV
      infection, have also been reported. However, data from western countries seem
      contradictory. In order to clarify and explore the molecular and epigenetic basis
      of HPV, CDKN2A status and role of microsatellite instability in the development
      of periocular sebaceous carcinoma, 24 cases of periocular sebaceous carcinoma
      were analyzed for the expression of p16(INK4a) and mismatch repair proteins
      (MLH1, MSH2, MSH6 and PMS2) via immunohistochemistry. Nested polymerase chain
      reaction (PCR) and genechip HPV typing were used to detect HPV infection and
      decide its genotype when present. PCR amplification using a consensus primer pair
      was also performed to detect beta-HPV. The methylation status of CDKN2A promoter
      region was studied by methylation-specific polymerase chain reaction. HPV
      positivity was demonstrated in only one of our cases (HPV 16), while another case
      showed p16(INK4a) overexpression. All cases showed preserved expression of
      mismatch repair proteins. CDKN2A promoter hypermethylation was noted in nearly
      half of our cases (11/24) and was associated with younger patient age (P = .013).
      Our results showed that periocular sebaceous carcinoma is rarely associated with
      HPV and microsatellite instability. Higher frequency of CDKN2A promoter
      hypermethylation in younger patients implies a significant epigenetic role in
      tumor development in this age group. 

PMID- 24440093
TI  - Association of increased osteopontin and splice variant-c mRNA expression with
      HER2 and triple-negative/basal-like breast carcinomas subtypes and recurrence.
AB  - Osteopontin, a secreted phosphoglycoprotein, promotes tumor progression through
      binding to integrins and CD44 cell receptors. Its overexpression has been
      correlated with metastasis and adverse outcome in several neoplasms. In breast
      carcinoma, osteopontin mRNA and its splicing variant-c, a suggested marker for
      transformed cells, have not been extensively analyzed. Immunohistochemistry was
      performed in 415 breast carcinomas to examine total osteopontin and osteopontin-c
      protein distribution. RNA was extracted and retrotranscribed to cDNA from 309
      tumors classified into immunophenotypes and in six cell lines representing the
      breast cancer subtypes. Total osteopontin and osteopontin-c mRNA levels were
      measured by quantitative RT-polymerase chain reaction. The median fold change of
      total osteopontin mRNA was higher in HER2-positive (fold-change = 14.7) and
      triple-negative/basal-like (fold-change = 14.7) tumors, whereas osteopontin-c
      mRNA was elevated in triple-negative/basal-like subtype (fold-change = 2.8).
      Total osteopontin levels were increased in SK-BR-3 (HER2-positive) and MDA-MB-468
      (triple-negative/basal-like) cell lines. Higher total and osteopontin-c mRNA
      levels were seen in tumors of high grade, with necrosis, positive nodal status
      and high Nothingam Prognostic Index score. Disease-free survival was
      significantly shorter for patients whose tumors overexpressed total osteopontin
      (67% vs 73%). Moreover, increased osteopontin-c stratified subgroups of patients
      at higher risk of recurrence among immunophenotypes, especially in triple
      negative/basal-like subtype (70% vs 83%). By multivariate analyses for disease
      free survival, osteopontin-c emerged as a significant predictor of relapse. In
      summary, our data showed an association of osteopontin with poor prognostic
      factors, aggressive subtypes HER2 and triple-negative/basal-like, and higher risk
      of recurrence. 

PMID- 24440094
TI  - Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and
      gallbladder carcinoma.
AB  - Sonic hedgehog (Shh) signaling has been extensively studied and is implicated in
      various inflammatory diseases and malignant tumors. We summarized the
      clinicopathological features and performed immunohistochemistry assays to examine
      expression of Shh signaling proteins in 10 normal mucosa, 32 gallbladder
      carcinoma (GBC), and 95 chronic cholecystitis (CC) specimens. The CC specimens
      were classified into three groups according to degree of inflammation. Compared
      with normal mucosa, CC, and GBC specimens exhibited increased expression of Shh.
      The immunoreactive score of Shh in the GBC group was higher than that in the mild
      to moderate CC groups but lower than that in the severe CC group (P < .05).
      Expression of Patched (Ptch) and Gli1 gradually increased from non-malignant
      cholecystitis to malignant tumors. Compared with CC specimens, GBC specimens
      showed higher cytoplasmic and membranous expression for Ptch (P < .05). Gli1
      staining showed cytoplasmic expression of Gli1 in both CC (60% for mild, 77% for
      moderate, and 84% for severe) and GBC specimens (97%). Nuclear expression of Gli1
      was detected in 16% of severe CC specimens with moderate to poor atypical
      hyperplasia, and in 62.5% of GBC specimens. Shh expression strongly correlated
      with expression of Ptch and Gli1. Furthermore, patients with strongly positive
      Gli1 staining had significantly lower survival rates than those with weakly
      positive staining. Our data indicate that the Shh signaling pathway is aberrantly
      activated in CC and GBC, and altered Shh signaling may be involved in the course
      of development from CC to gallbladder carcinogenesis.

PMID- 24440095
TI  - Primary anorectal Hodgkin lymphoma: report of a case and review of the
      literature.
AB  - Primary colorectal lymphomas are very rare. They are mostly B-cell non-Hodgkin
      lymphomas. Only 2 cases of anorectal Hodgkin lymphoma have been described so far,
      both affecting HIV-infected males and showing Epstein-Barr virus infection. We
      report an unusual case of primary Hodgkin lymphoma of the anorectal region in an
      HIV-negative, Epstein-Barr virus-infected patient and in the absence of
      inflammatory bowel disease. The importance of distinguishing Hodgkin lymphoma
      from Epstein-Barr virus-induced lymphoproliferative disorders and from Epstein
      Barr virus-positive diffuse large B-cell lymphoma of the elderly is stressed in
      particular in non-immunocompromised patients and in the absence of history of
      inflammatory bowel disease. 

PMID- 24440096
TI  - Combined multivariate data analysis of high-performance thin-layer chromatography
      fingerprints and direct analysis in real time mass spectra for profiling of
      natural products like propolis.
AB  - Sophisticated statistical tools are required to extract the full analytical power
      from high-performance thin-layer chromatography (HPTLC). Especially, the
      combination of HPTLC fingerprints (image) with chemometrics is rarely used so
      far. Also, the newly developed, instantaneous direct analysis in real time mass
      spectrometry (DART-MS) method is perspective for sample characterization and
      differentiation by multivariate data analysis. This is a first novel study on the
      differentiation of natural products using a combination of fast fingerprint
      techniques, like HPTLC and DART-MS, for multivariate data analysis. The results
      obtained by the chemometric evaluation of HPTLC and DART-MS data provided
      complementary information. The complexity, expense, and analysis time were
      significantly reduced due to the use of statistical tools for evaluation of
      fingerprints. The approach allowed categorizing 91 propolis samples from Germany
      and other locations based on their phenolic compound profile. A high level of
      confidence was obtained when combining orthogonal approaches (HPTLC and DART-MS)
      for ultrafast sample characterization. HPTLC with selective post-chromatographic
      derivatization provided information on polarity, functional groups and spectral
      properties of marker compounds, while information on possible elemental formulae
      of principal components (phenolic markers) was obtained by DART-MS. 

PMID- 24440097
TI  - Simultaneous determination of oxathiapiprolin and two metabolites in fruits,
      vegetables and cereal using a modified quick, easy, cheap, effective, rugged, and
      safe method and liquid chromatography coupled to tandem mass spectrometry.
AB  - An effective and rapid analytical method for the simultaneous determination of a
      new fungicide oxathiapiprolin and its metabolites (IN-E8S72 and IN-WR791)
      residues in fruits (grape, watermelon, watermelon peel), vegetables (cucumber,
      tomato, potato) and cereal (wheat) was developed by ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) using the modified quick,
      easy, cheap, effective, rugged, and safe (QuEChERS) extraction concept. Three
      target compounds were extracted from all matrices with 1% (V/V) formic acid
      aqueous solution and acetonitrile then cleaned by dispersive solid phase
      extraction (dSPE) with octadecylsilane (C18) and graphitized carbon black (GCB).
      The determination of the target compounds was achieved within a 5.1min run time
      by using an UPLC HSS T3 column connected to an electrospray ionization source
      (ESI, positive ion mode) for oxathiapiprolin and the negative mode for the two
      metabolites. The method showed excellent linearity (R(2)>0.9904) for target
      compounds. The limit of detection (LOD) for the three compounds ranged from
      0.5MUgkg(-1) to 7.5MUgkg(-1) and the limits of quantitation (LOQ) were 1MUgkg(-1)
      and 10MUgkg(-1) for oxathiapiprolin and the metabolites, respectively. The mean
      recoveries from seven matrices ranged from 81.5 to 110.7%, with intra-day
      relative standard deviations (RSDr) in the range of 0.8-12.0% for all three test
      compounds. The inter-day RSDR were less than 14.5% for all of the recovery tests.
      The method was successfully applied for simultaneous analysis of oxathiapiprolin
      and its metabolites in actual trial samples, indicating its effectiveness in
      investigating oxathiapiprolin and its metabolites in the food. 

PMID- 24440098
TI  - Expression and prognostic relevance of centromere protein A in primary
      osteosarcoma.
AB  - Centromere protein A (CENP-A) is one of the fundamental components of the human
      active kinetochore and plays important roles in cell-cycle regulation, cell
      survival, and genetic stability. The aim of the present study was to explore the
      expression and prognostic significance of CENP-A in osteosarcoma. The results of
      real-time quantitative PCR and Western blotting analysis revealed an enhanced
      expression of CENP-A in osteosarcomas relative to adjacent non-tumorous bone
      tissues at both mRNA and protein levels. Immunohistochemically, 72 of the 123
      osteosarcoma specimens (58.5%) had high expression of CENP-A. CENP-A
      overexpression was significantly correlated with tumor size (P=0.002), poor
      response to neoadjuvant chemotherapy (P=0.016), local recurrence/lung metastasis
      (P=0.001), high Ki-67 index (P=0.004), and P53 positivity (P=0.005). Median
      overall and recurrence-free survival time was significantly shorter in patients
      with high-CENP-A osteosarcomas than in those with low-CENP-A osteosarcomas.
      Multivariate analysis identified CENP-A as an independent poor prognostic factor
      for osteosarcoma. In conclusion, our results demonstrate that elevated CENP-A
      expression is significantly associated with osteosarcoma progression and has an
      independent prognostic value in predicting overall and recurrence-free survival
      for patients with osteosarcoma. 

PMID- 24440099
TI  - The variable pathologic presentations of medullary and micro-medullary thyroid
      carcinoma: an institutional experience.
AB  - Medullary thyroid carcinoma (MTC) is a rare tumor; its pathologic diagnosis can
      be difficult due to variability in its clinical presentation, size, morphology,
      and follow-up. We report our institutional experience with 45 cases of MTC
      diagnosed at University of Pennsylvania Medical Center between 2000 and 2007. The
      collected data points included patient's age, sex, family history, tumor size,
      method of diagnosis, calcitonin and CEA levels, presence of concomitant
      follicular derived thyroid carcinoma (FDTC), lymph node (LN) status, and clinical
      follow-up. The cohort included 17 males and 28 females (average age 53 years); 6
      had a history of multiple endocrine neoplasia II (MENII). Pre-operative FNA was
      performed in 33/45 cases (33%); 23/33 were diagnosed as MTC or suspicious for
      MTC. Of 45 cases 20 were micro-MTC; 15 occurred with other thyroid malignancies.
      LN metastases were present at primary resection in 18/45 cases. Calcitonin levels
      rose or remained elevated postoperatively in 4 cases; of these, 2 had regional LN
      recurrence and 1 developed distant metastases and subsequently died of disease.
      MTC is a heterogeneous disease. Sporadic micro-MTC carcinoma is an indolent tumor
      and can occur with other malignant tumors of the thyroid gland. 

PMID- 24440100
TI  - Clinical trials transparency and the Trial and Experimental Studies Transparency
      (TEST) act.
AB  - Clinical trial research is the cornerstone for successful advancement of medicine
      that provides hope for millions of people in the future. Full transparency in
      clinical trials may allow independent investigators to evaluate study designs,
      perform additional analysis of data, and potentially eliminate duplicate studies.
      Current regulatory system and publishers rely on investigators and pharmaceutical
      industries for complete and accurate reporting of results from completed clinical
      trials. Legislation seems to be the only way to enforce mandatory disclosure of
      results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was
      introduced to the legislators in the United States to promote greater
      transparency in research industry. Public safety and advancement of science are
      the driving forces for the proposed policy change. The TEST Act may benefit the
      society and researchers; however, there are major concerns with participants'
      privacy and intellectual property protection. 

PMID- 24440101
TI  - Reading performance of monofocal pseudophakic patients with and without glasses
      under normal and dim light conditions.
AB  - PURPOSE: To evaluate reading performance of patients with monofocal intraocular
      lenses (IOLs) (Acrysof SN60WF) with or without reading glasses under bright and
      dim light conditions. SETTING: Austrian Academy of Ophthalmology, Vienna,
      Austria. DESIGN: Evaluation of a diagnostic test or technology. METHODS: In
      pseudophakic patients, the spherical refractive error was limited to between
      +0.50 diopter (D) and -0.75 D with astigmatism of 0.75 D (mean spherical
      equivalent: right eye, -0.08 +/- 0.43 [SD]; left eye, -0.15 +/- 0.35). Near
      addition was +2.75 D. Reading performance was assessed binocularly with or
      without reading glasses at an illumination of 100 candelas (cd)/m(2) and 4
      cd/m(2) using the Radner Reading Charts. RESULTS: In the 25 patients evaluated,
      binocularly, the mean corrected distance visual acuity was -0.07 +/- 0.06 logMAR
      and the mean uncorrected distance visual acuity was 0.01 +/- 0.11 logMAR. The
      mean reading acuity with reading glasses was 0.02 +/- 0.10 logRAD at 100 cd/m(2)
      and 0.12 +/- 0.14 logRAD at 4 cd/m(2). Without reading glasses, it was 0.44 +/-
      0.13 logRAD and 0.56 +/- 0.16 logRAD, respectively (P < .05). Without reading
      glasses and at 100 cd/m(2), 40% of patients read 0.4 logRAD at more than 80 words
      per minute (wpm), 68% exceeded this limit at 0.5 logRAD, and 92% exceeded it at
      0.6 logRAD. The mean reading speed at 0.5 logRAD was 134.76 +/- 48.22 wpm; with
      reading glasses it was 167.65 +/- 32.77 wpm (P < .05). CONCLUSION: A considerable
      percentage of patients with monofocal IOLs read newspaper print size without
      glasses under good light conditions.

PMID- 24440102
TI  - Correction of moderate corneal astigmatism during cataract surgery: toric
      intraocular lens versus peripheral corneal relaxing incisions.
AB  - PURPOSE: To compare the astigmatism-reducing effect of a toric intraocular lens
      (IOL) and peripheral corneal relaxing incisions (PCRIs). SETTING: Moorfields Eye
      Hospital NHS Foundation Trust, London, United Kingdom. DESIGN: Prospective masked
      bilateral randomized study. METHODS: Cataract patients with a preoperative
      corneal astigmatism of 1.0 to 2.5 diopters (D) were included. All patients
      received a toric IOL in 1 eye and a nontoric IOL plus a PCRI in the other eye.
      Postoperative follow-up was at 1 hour, 1 month, and 6 months. The uncorrected
      distance visual acuity, corrected distance visual acuity, autorefraction (Topcon
      RM-8800), and subjective refraction were recorded. The IOL axis was assessed
      using retroillumination photographs. RESULTS: The study enrolled 60 eyes of 30
      patients. The mean astigmatism vector reduction was 1.74 D +/- 0.64 (SD) in the
      toric IOL group and 1.27 +/- 0.76 D in the PCRI group; the difference was
      statistically significant (P=.042). The mean absolute rotation of the toric IOL
      was 2.5 +/- 1.8 degrees (maximum 6.3 degrees) in the first 6 postoperative
      months. Astigmatism increased in the PCRI group between the 1-month and 6-month
      follow-up (mean 0.38 +/- 0.27 D; maximum 1.00 D) (P<.001). CONCLUSION: Toric IOLs
      and PCRIs both reduced astigmatism; however, toric IOLs reduced astigmatism to a
      higher extent and they were more predictable.

PMID- 24440103
TI  - Plea for femtosecond laser pre-treatment and cataract surgery in the same room.

PMID- 24440104
TI  - Risk factors for acute postoperative intraocular pressure elevation after
      phacoemulsification in glaucoma patients.
AB  - PURPOSE: To evaluate the risk factors for and frequency of an acute intraocular
      pressure (IOP) elevation (spike) after phacoemulsification in patients with
      glaucoma. SETTING: Academic glaucoma clinics and operating rooms. DESIGN:
      Retrospective case series. METHODS: Charts of consecutive glaucoma patients
      without previous incisional glaucoma surgery having phacoemulsification by the
      same surgeon between August 1996 and July 2012 were reviewed to obtain
      demographic information, preoperative glaucoma medications, severity and
      treatment measures, intraoperative course, and postoperative outcomes. A
      postoperative IOP spike was defined as IOP greater than 50% above baseline IOP.
      Main outcome measures were the number of eyes with a postoperative IOP spike and
      risk factors associated with an IOP spike after phacoemulsification. RESULTS: Of
      271 eyes (271 patients) included in the study, 45 (17%) had an IOP spike. Risk
      factors for postoperative IOP spike by multivariate analysis included longer
      axial length (AL) or associated characteristics (wider angle grade on gonioscopy,
      deeper anterior chamber, and male sex), higher number of preoperative IOP
      lowering medications, previous laser trabeculoplasty, and lack of postoperative
      oral acetazolamide. One eye (0.4%) required trabeculectomy during the 90-day
      postoperative period. CONCLUSIONS: A significant proportion of glaucoma patients
      having phacoemulsification had an IOP spike. Patients requiring a higher number
      of IOP-lowering medications or laser trabeculoplasty for IOP control
      preoperatively and those with a greater AL should be treated more aggressively
      with IOP-lowering medication in the immediate postoperative period. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24440105
TI  - Outcomes of torsional microcoaxial phacoemulsification using tips with 30-degree
      and 45-degree aperture angles.
AB  - PURPOSE: To compare the safety and efficacy of Ozil Intelligent Phaco torsional
      microcoaxial phacoemulsification surgeries performed using 30-degree and 45
      degree aperture angled tips. SETTING: Maltepe University School of Medicine
      Department of Ophthalmology, Istanbul, Turkey. DESIGN: Comparative case series.
      METHODS: Eyes were assigned to 2.2 mm microcoaxial phacoemulsification using the
      torsional mode with a 45-degree (Group 1) or 30-degree (Group 2) aperture angled
      tip. A quick-chop surgical technique was used. The primary outcome measures were
      ultrasound time (UST), cumulative dissipated energy (CDE), longitudinal and
      torsional ultrasound (US) amplitudes, mean surgical time, mean balanced salt
      solution volume used, and mean central corneal thickness (CCT) changes. RESULTS:
      The mean UST, CDE, and longitudinal and torsional US amplitudes were 58.21
      seconds +/- 33.81 (SD), 7.74 +/- 6.23, 0.45 +/- 0.30, and 26.30 +/- 12.60 in
      Group 1 and 63.83 +/- 23.42 seconds, 12.36 +/- 6.75, 0.23 +/- 0.26, and 44.65 +/-
      14.38 in Group 2, respectively. The mean CDE and torsional amplitudes were
      significantly lower in Group 1 (P=.002 and P=.001, respectively). The mean
      balanced salt solution volume was 73.30 +/- 19.87 cc in Group 1 and 74.30 +/-
      19.44 cc in Group 2 (P=.821). The mean CCT change was 52.40 +/- 38.08 MUm and
      99.35 +/- 47.14 MUm, respectively (P<.001). CONCLUSION: Torsional
      phacoemulsification performed with a 45-degree aperture angled tip provided more
      effective lens removal with a lower CDE and less CCT change than a 30-degree
      aperture angled tip.

PMID- 24440106
TI  - Systemic lupus erythematosus with polyarthralgias due to myelofibrosis in a 49
      year-old female.

PMID- 24440107
TI  - Microbial adherence to cosmetic contact lenses.
AB  - AIM: To investigate whether cosmetic contact lenses (CCL) with surface pigments
      affect microbial adherence. METHOD: Fifteen brands of CCL were purchased from
      optical, non-optical retail outlets, and via the Internet. A standardized rub-off
      test was performed on each CCL (five lenses per brand) to confirm the location of
      the pigments. The rub-off test comprised gentle rubbing on the surfaces of each
      CCL with wetted cotton buds for a maximum of 20 rubs per surface. A new set of
      CCL (five lenses per brand) were incubated in Pseudomonas aeruginosa overnight.
      Viable counts of adhered bacteria were determined by the number of colony-forming
      units (CFU) on agar media on each lens. The adherence of P. aeruginosa as well as
      Staphylococcus aureus and Serratia marcescens to three brands of CCL (A-C) (five
      lenses per brand) were also compared to their adherences on their clear
      counterparts. RESULTS: Only two of the 15 brands of CCL tested (brands B and C)
      had pigments that did not detach with the rub-off test. The remaining 13 brands
      of CCL all failed the rub-off test and these lenses showed higher P. aeruginosa
      adherence (8.7 * 10(5)-1.9 * 10(6) CFU/lens). Brands B and C lenses showed at
      least six times less bacterial adhesion than the other 13 brands. Compared to
      their clear counterparts, bacterial adherence to brands B and C lenses did not
      differ significantly, whereas brand A lenses showed significantly higher
      adherence. CONCLUSION: Surface pigments on CCL resulted in significantly higher
      bacterial adherence.

PMID- 24440108
TI  - Local recurrence of a bronchial carcinoid tumour.

PMID- 24440109
TI  - Empyema necessitatis following chest trauma.

PMID- 24440110
TI  - Analysis of left ventricular volumes and function: a multicenter comparison of
      cardiac magnetic resonance imaging, cine ventriculography, and unenhanced and
      contrast-enhanced two-dimensional and three-dimensional echocardiography.
AB  - BACKGROUND: Contrast echocardiography improves accuracy and reduces interreader
      variability on left ventricular (LV) functional analyses in the setting of two
      dimensional (2D) echocardiography. The need for contrast imaging using three
      dimensional (3D) echocardiography is less defined. The aim of this multicenter
      study was to define the accuracy and interreader agreement of unenhanced and
      contrast-enhanced 2D and 3D echocardiography for the assessment of LV volumes and
      ejection fraction (EF). METHODS: A multicenter, open-label study was conducted
      including 63 patients, using intrasubject comparisons to assess the agreement of
      unenhanced and contrast-enhanced 2D and 3D echocardiography as well as calibrated
      biplane cine ventriculography with cardiac magnetic resonance for the
      determination of LV volumes and EF. Each of the imaging techniques used to define
      LV function was assessed by two independent, off-site readers unaware of the
      results of the other imaging techniques. RESULTS: LV end-systolic and end
      diastolic volumes were underestimated by 2D and 3D unenhanced echocardiography
      compared with cardiac magnetic resonance. Contrast enhancement resulted in
      similar significant increases in LV volumes on 2D and 3D echocardiography. The
      mean percentage of interreader variability for LV EF was reduced from 14.3% (95%
      confidence interval [CI], 11.7%-16.8%) for unenhanced 2D echocardiography and
      14.3% (95% CI, 9.7%-18.9%) for unenhanced 3D echocardiography to 8.0% (95% CI,
      6.3%-9.7%; P < .001) for contrast-enhanced 2D echocardiography and 7.4% (95% CI,
      5.7%-9.1%; P < .01) for contrast-enhanced 3D echocardiography and thus to a
      similar level as for cardiac magnetic resonance (7.9%; 95% CI, 5.4%-10.5%). A
      similar effect was observed for interreader variability for LV volumes.
      CONCLUSIONS: Contrast administration on 3D echocardiography results in improved
      determination of LV volumes and reduced interreader variability. The use of 3D
      echocardiography requires contrast application as much as 2D echocardiography to
      reduce interreader variability for volumes and EF.

PMID- 24440111
TI  - Parent attitudes about school-located influenza vaccination clinics.
AB  - The use of alternative venues beyond physician offices may help to increase rates
      of population influenza vaccination. Schools provide a logical setting for
      reaching children, but most school-located vaccination (SLV) efforts to date have
      been limited to local areas. The potential reach and acceptability of SLV at the
      national level is unknown in the United States. To address this gap, we conducted
      a nationally representative online survey of 1088 parents of school-aged
      children. We estimate rates of, and factors associated with, future hypothetical
      parental consent for children to participate in SLV for influenza. Based on
      logistic regression analysis, we estimate that 51% of parents would be willing to
      consent to SLV for influenza. Among those who would consent, SLV was reported as
      more convenient than the regular location (42.1% vs. 19.9%, P<0.001). However the
      regular location was preferred over SLV for the child's well-being in case of
      side effects (46.4% vs. 20.9%, P<0.001) and proper administration of the vaccine
      (31.0% vs. 21.0%, P<0.001). Parents with college degrees and whose child received
      the 2009-2010 seasonal or 2009 H1N1 influenza vaccination were more likely to
      consent, as were parents of uninsured children. Several measures of concern about
      vaccine safety were negatively associated with consent for SLV. Of those not
      against SLV, schools were preferred as more convenient to the regular location by
      college graduates, those whose child received the 2009-2010 seasonal or 2009 H1N1
      influenza vaccination, and those with greater travel and clinic time. With an
      estimated one-half of U.S. parents willing to consent to SLV, this study shows
      the potential to use schools for large-scale influenza vaccination programs in
      the U.S. 

PMID- 24440112
TI  - Revaccination with 7-valent pneumococcal conjugate vaccine elicits better
      serologic response than 23-valent pneumococcal polysaccharide vaccine in HIV
      infected adult patients who have undergone primary vaccination with 23-valent
      pneumococcal polysaccharide vaccine in the era of combination antiretroviral
      therapy.
AB  - HIV-infected adults who had received 23-valent pneumococcal polysaccharide
      vaccine (PPV23) five years or more earlier consecutively underwent revaccination
      with one dose of PPV23 (127 subjects) from December 2005 through October 2007, or
      upon change in standard of care, non-randomly one (50) or two doses (44) of 7
      valent pneumococcal conjugate vaccine (PCV7) from October 2008 through June 2010.
      Serologic response was defined as >= 2-fold increase in the IgG level plus a
      level >= 1000ng/ml 48 weeks following revaccination. At week 48, the response
      rate was significantly higher in the 2-dose PCV7 group compared with that in the
      1-dose PCV7 or PPV23 group (63.6% vs 32.0% vs 8.7%, respectively; P<0.05).
      Revaccination with one dose of PCV7 (AOR, 4.57), two doses of PCV7 (AOR, 22.66),
      and CD4 >350 cells/MUl (AOR, 3.24) and undetectable viral load (AOR, 3.87) at
      revaccination were statistically significantly associated with a better serologic
      response at week 48. Despite the limitation that study arms were neither
      randomized nor contemporaneous, we conclude that revaccination with PCV7 appears
      to elicit a better serologic response than PPV23 in the HIV-infected adults who
      have received PPV23 five years or more earlier (clinical trial registration
      number: NCT00885625).

PMID- 24440113
TI  - Increased emergency room visits or hospital admissions in females after 12-month
      MMR vaccination, but no difference after vaccinations given at a younger age.
AB  - BACKGROUND: Previous studies have suggested that a child's sex may be a predictor
      of vaccine reactions. METHODS: We used a self-controlled case series design, an
      extension of retrospective cohort methodology which controls for fixed
      confounders using a conditional Poisson modeling approach. We compared a risk
      period immediately following vaccination to a control period farther removed from
      vaccination in each child and estimated the relative incidence of emergency room
      visits and/or hospital admissions following the 2-, 4-, 6-, and 12-month
      vaccinations to investigate the effect of sex on relative incidence. All infants
      born in Ontario, Canada between April 1, 2002 and March 31, 2009 were eligible
      for study inclusion. RESULTS: In analyses combining immunizations at 2, 4 and 6
      months and examining these vaccinations separately, there was no significant
      relationship between the relative incidence of an event and sex of the child. At
      12 months, we observed a significant effect of sex, with female sex being
      associated with a significantly higher relative incidence of events (P=0.0027).
      The relative incidence ratio (95% CI) comparing females to males following the 12
      month vaccination was 1.08 (1.03 to 1.14), which translates to 192 excess events
      per 100,000 females vaccinated compared to the number of events that would have
      occurred in 100,000 males vaccinated. CONCLUSIONS: As the MMR vaccine is given at
      12 months of age in Ontario, our findings suggest that girls may have an
      increased reactogenicity to the MMR vaccine which may be indicative of general
      sex differences in the responses to the measles virus.

PMID- 24440114
TI  - Characterization of the structural modifications accompanying the loss of HBsAg
      particle immunogenicity.
AB  - The aim of this work was to further understand the relationship between the
      immunogenicity and the structure of Hepatitis B surface antigen (HBsAg) particles
      used in Hepatitis B vaccines. To reach this aim, we compared by using a large
      range of techniques, the structure and properties of untreated particles with
      those of particles stored for 3 weeks at +60 degrees C, a treatment which
      resulted in a loss of HBsAg antigenicity (toward RF-1 mAb) and immunogenicity (in
      mice). While untreated particles imaged by electron microscopy and atomic force
      microscopy appeared as isolated nanoparticles of ~ 20nm, heated particles
      appeared as long chains of particle aggregates with a partial loss of their
      protein protrusions. Moreover, infrared spectroscopy and circular dichroism
      revealed that the secondary structure of the S proteins was significantly
      affected, with a loss of 10% of their alpha-helix content. Steady-state and time
      resolved fluorescence data further revealed strong modifications of the most
      emitting Trp residues at the particle surface, confirming significant changes in
      the conformation of the S proteins. Moreover, modifications in the organization
      of both the lipid core and lipid membrane surface of the heated particles were
      evidenced by environment-sensitive 3-hydroxyflavone probes. Taken together, our
      data evidenced a clear relationship between the bona fide S protein structure and
      lipid organization notably at the particle surface and the particle
      immunogenicity. 

PMID- 24440116
TI  - Inhibition and the right inferior frontal cortex: one decade on.
AB  - In our TICS Review in 2004, we proposed that a sector of the right inferior
      frontal cortex (rIFC) in humans is critical for inhibiting response tendencies.
      Here we survey new evidence, discuss ongoing controversies, and provide an
      updated theory. We propose that the rIFC (along with one or more fronto-basal
      ganglia networks) is best characterized as a brake. This brake can be turned on
      in different modes (totally, to outright suppress a response; or partially, to
      pause), and in different contexts (externally, by stop or salient signals; or
      internally, by goals). We affirm inhibition as a central component of executive
      control that relies upon the rIFC and associated networks, and explain why rIFC
      disruption could generally underpin response control disorders. 

PMID- 24440115
TI  - Reworking the language network.
AB  - Prior investigations of functional specialization have focused on the response
      profiles of particular brain regions. Given the growing emphasis on regional
      covariation, we propose to reframe these questions in terms of brain 'networks'
      (collections of regions jointly engaged by some mental process). Despite the
      challenges that investigations of the language network face, a network approach
      may prove useful in understanding the cognitive architecture of language. We
      propose that a language network plausibly includes a functionally specialized
      'core' (brain regions that coactivate with each other during language processing)
      and a domain-general 'periphery' (a set of brain regions that may coactivate with
      the language core regions at some times but with other specialized systems at
      other times, depending on task demands). Framing the debate around network
      properties such as this may prove to be a more fruitful way to advance our
      understanding of the neurobiology of language. 

PMID- 24440117
TI  - Opioid antagonism impairs acquisition of forebrain-dependent trace-associative
      learning: an eyeblink conditioning analysis.
AB  - While the opioid system is predominantly known for its properties governing
      nociception, it has also been found to play a role in learning and memory. Opioid
      involvement in task acquisition and retention has been examined using various
      associative paradigms. These analyses have demonstrated that depending upon the
      associative paradigm and timing of opioid modulation relative to the task, it can
      either impair acquisition or facilitate memory consolidation. However, opioid
      involvement in forebrain-dependent trace-associative learning paradigms has never
      been examined. In associative paradigms, a subject learns to associate two
      stimuli, while in trace paradigms the two stimuli are separated in time, which is
      thought to increase task difficulty due to utilization of forebrain structures.
      The current analysis utilized the trace paradigm whisker-trace-eyeblink (WTEB)
      conditioning with a trace interval of 250 ms, in conjunction with pre- and post
      training opioid inhibition with naloxone, a well-characterized nonspecific opioid
      antagonist. Naloxone administration prior to training (pre-training) was found to
      significantly impair acquisition of the WTEB association; however, administration
      following training (post-training) did not significantly differ from saline
      controls. These findings demonstrate that opioid inhibition impairs acquisition
      of forebrain-dependent trace-associations, further suggesting that opioid
      activation plays a modulatory role in trace-acquisition. Prior behavioral
      analyses have suggested that hippocampal MU-opioid receptors are most likely
      facilitating this effect; however, subsequent analyses will be needed to
      determine the specific brain region(s) and opioid receptor subtype(s) mediating
      this effect.

PMID- 24440118
TI  - The 5-HT1A receptor C(1019)G polymorphism influences the intravaginal ejaculation
      latency time in Dutch Caucasian men with lifelong premature ejaculation.
AB  - INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent
      intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been
      postulated as a neurobiological dysfunction related to diminished serotonergic
      neurotransmission with 5-HT1A receptor hyperfunction and 5-HT2C hypofunction.
      AIM: To investigate the relationship between 5-HT1A receptor gene (HTR1A)
      C(1019)G promoter polymorphism and IELT in men with LPE. This polymorphism is
      known to increase 5-HT1A receptor expression. METHODS: A prospective study was
      conducted in 54 Dutch Caucasian men with LPE. Baseline IELT during coitus was
      assessed by stopwatch over a 1-month period. All men were genotyped for HTR1A
      gene polymorphism. Allele frequencies and genotypes of C and G variants of HTR1A
      polymorphism were determined. Association between CC, CG, and GG genotypes and
      the IELT in men with LPE were investigated. MAIN OUTCOME MEASURES: IELT measured
      by stopwatch, HTR1A polymorphism. RESULTS: In this cohort of men with LPE, the
      geometric mean IELT was 23.8 s. Of the 54 men, the CC, CG and GG genotype
      frequency for the C(1019)G polymorphism of the 5-HT1A gene was 33%, 43% and 24%,
      respectively. The geometric mean IELT for the CC, CG and GG genotypes were 14.5,
      27.7 and 36.0 s, respectively (p=0.019). Compared to GG and CG genotypes, men
      with CC genotype had a 250% and 190% shorter ejaculation time, respectively.
      CONCLUSIONS: HTR1A gene polymorphism is associated with the IELT in men with LPE.
      Men with CC genotype have shorter IELTs than men with GG and CG genotypes.

PMID- 24440119
TI  - Using a conflict conceptual framework to describe challenges to coordinated
      patient care from the physicians' and pharmacists' perspective.
AB  - BACKGROUND: In an effort to increase cost-effectiveness of health care and reduce
      overall costs, patient-centered medical homes have been proposed to spur
      fundamental changes in the way primary care is delivered. One of the chief
      principles that describe a patient-centered medical home is that care is
      organized across all elements of the broader health care system, including
      community pharmacies. OBJECTIVES: To identify and describe challenges derived
      from a conflict management framework to a physician-pharmacist approach to
      coordinating patient care. METHODS: A descriptive, exploratory, non-experimental
      study was conducted in Wisconsin (U.S. State) from June to December, 2011. Data
      were collected through two rounds of face-to-face interviews with physicians and
      community pharmacists. The first round involved one-on-one interviews with
      pharmacists and physicians. The second round brought pharmacist-physician dyads
      together in an open-ended interview exploring issues raised in the first round.
      Content analysis was guided by a conflict management conceptual framework using
      NVivo 10 qualitative software. RESULTS: A total of four major themes emerged from
      the conflict analysis of interviews that illustrate challenges to coordinated
      patient care: Scarce resources, technology design and usability, insurance
      constraints, and laws and policy governing patient care. The study findings
      indicate that both groups of health care professionals work within an environment
      of conflict and have to negotiate the challenges and strains that exist in the
      current health care system. Their need to work together, or interdependence, is
      primarily challenged by scarce resources and external interference. CONCLUSIONS:
      Efforts to coordinate patient care through teams of inter-professional health
      care providers will be more successful if they acknowledge the inherent conflict
      that exists. Efforts should be made to provide an infrastructure for
      interdependence and to support interpersonal communication.

PMID- 24440120
TI  - Applying the WHO recommendations on health-sector response to violence against
      women to assess the Spanish health system. A mixed methods approach.
AB  - This methodological note describes the development and application of a mixed
      methods protocol to assess the responsiveness of Spanish health systems to
      violence against women in Spain, based on the World Health Organization (WHO)
      recommendations. Five areas for exploration were identified based on the WHO
      recommendations: policy environment, protocols, training,
      accountability/monitoring, and prevention/promotion. Two data collection
      instruments were developed to assess the situation of 17 Spanish regional health
      systems (RHS) with respect to these areas: 1) a set of indicators to guide a
      systematic review of secondary sources, and 2) an interview guide to be used with
      26 key informants at the regional and national levels. We found differences
      between RHSs in the five areas assessed. The progress of RHSs on the WHO
      recommendations was notable at the level of policies, moderate in terms of health
      service delivery, and very limited in terms of preventive actions. Using a mixed
      methods approach was useful for triangulation and complementarity during
      instrument design, data collection and interpretation. 

PMID- 24440121
TI  - Pre- and post-stimulus EEG patterns associated with the touch-induced illusory
      flash.
AB  - Pairing two brief auditory beeps with a single flash can evoke the percept of a
      second, illusory, flash. Investigations of the underlying neural mechanisms are
      limited to post-stimulus effects of this sound-induced illusory flash. We
      investigated whether touch modulates the visual evoked potential in a similar
      vein, and also looked at pre-stimulus activity. Electroencephalogram (EEG) was
      recorded over occipital and parieto-occipital areas of 12 observers. We compared
      bimodal EEG to its unimodal constituents (i.e., the difference waves) and found
      significant positive deflections around 110 ms and 200 ms and negative
      deflections around 330 ms and 390 ms from stimulus onset. These results are
      similar to those reported for the sound-induced illusion, albeit somewhat later.
      Furthermore, comparison of the EEG activity between those trials in which the
      illusion was perceived and those in which it was absent revealed that the phase
      of pre-stimulus alpha was linked to perceiving the illusion or not. We conclude
      that touch can modulate activity in the visual cortex and that similar neural
      mechanisms underlie perception of the sound- and touch-induced illusory flash and
      that the phase of the alpha wave at the moment of presentation that affects
      perception.

PMID- 24440122
TI  - Evaluation of semen quality in roosters of different age during hot climatic
      condition.
AB  - The present experiment was conducted to evaluate the semen quality of roosters of
      different ages during hot climatic condition. Semen from roosters (n=8/age group)
      of 23, 42 and 65 weeks of age was collected and evaluated for different physical
      parameters. The sperm membrane integrity was evaluated by hypo-osmotic swelling
      test, whereas sperm DNA fragmentation was assessed by Sperm Chromatin Dispersion
      (SCD) test. The seminal plasma cortisol level was assessed by EIA. The shed
      average Temperature Humidity Index (THI) during the experiment period was 79.32.
      Semen volume and sperm DNA fragmentation were significantly different (P<=0.05)
      between the age groups tested. Roosters of 42 weeks age had higher semen volume
      and lower sperm DNA fragmentation during study period. None of the other
      parameters were influenced by the age of the birds. The results indicated that
      semen quality was affected by the age of the birds. The extreme heat condition
      also appears to exert a negative influence on the sperm chromatin in roosters. 

PMID- 24440123
TI  - Spatial accessibility of drug treatment facilities and the effects on locus of
      control, drug use, and service use among heroin-injecting Mexican American men.
AB  - BACKGROUND: This study explores the spatial accessibility of outpatient drug
      treatment facilities and the potential relationship with drug use-related
      outcomes among Mexican American heroin users. METHODS: Secondary data on 219
      current and former heroin-injecting Mexican American men aged 45 and older were
      drawn from a research study in Houston, Texas. We used geographic information
      systems (GIS) to derive two spatial accessibility measures: distance from one's
      place of residence to the closest drug treatment facility (in minutes); and the
      number of facilities within a 10-minute driving distance from one's place of
      residence. Exploratory logistic regression analyses examined the association
      between the spatial accessibility of drug treatment facilities and several drug
      use-related outcomes: internal locus of control (LOC); perceived chances and
      worries of injecting in the next six months; treatment utilization; and location
      of last heroin purchase. RESULTS: Participants with greater spatial access to
      treatment programs were more likely to report a higher chance of injecting in the
      near future. However, while current heroin users were more worried about
      injecting in the next six months, greater spatial access to treatment programs
      seemed to have a buffering effect. Finally, those who lived closer to a treatment
      programs were more likely to have last purchased heroin inside the neighborhood
      versus outside the neighborhood. Spatial accessibility was not associated with
      internal LOC or treatment utilization. CONCLUSION: The findings showed that the
      presence of outpatient treatment facilities-particularly services in Spanish-may
      influence perceived risk of future heroin use and purchasing behaviors among
      Mexican American men. Implications for future spatially-informed drug use
      research and the planning of culturally and linguistically responsive drug
      treatment programs are discussed.

PMID- 24440124
TI  - Energetic communication between functional sites of the gene-3-protein during
      infection by phage fd.
AB  - To initiate infection of Escherichia coli, phage fd uses its gene-3-protein (G3P)
      to bind first to an F pilus and then to the TolA protein at the cell surface. G3P
      is normally auto-inhibited because a tight interaction between the two N-terminal
      domains N1 and N2 buries the TolA binding site. Binding of N2 to the pilus
      activates G3P by initiating long-range conformational changes that are relayed to
      the domain interface and to a proline timer. We discovered that the 23-28 loop of
      the N1 domain is critical for propagating these conformational signals. The
      analysis of the stability and the folding dynamics of G3P variants with a
      shortened loop combined with TolA interaction studies and phage infection
      experiments reveal how the contact between the N2 domain and the 23-28 loop of N1
      is energetically linked with the interdomain region and the proline timer and how
      it affects phage infectivity. Our results illustrate how conformational
      transitions and prolyl cis/trans isomerization can be coupled energetically and
      how conformational signals to and from prolines can be propagated over long
      distances in proteins. 

PMID- 24440125
TI  - Comment on "Surface tension of concentrated electrolyte solutions" (R.I.
      Slavchov, J.K. Novev, J. Colloid Interface Sci. 387 (2012) 234).

PMID- 24440126
TI  - [Esophageal atresia: prevalence, prenatal diagnosis and prognosis].
AB  - Esophageal atresia (EA) is a rare congenital malformation (1 in 2,500 to 3,500
      births). Prenatal diagnosis (PN) is particularly interesting allowing search for
      associated malformations related to worse prognosis forms (reference ultrasound,
      MRI and amniocentesis) and planning the birth in an adapted medico-surgical
      center. Diagnosis of EA is usually suspected because of indirect and non-specific
      signs: association of polyhydramnios and absent or small stomach bubble. The
      visualization in ultrasound or MRI of cervical or thoracic fluid image
      corresponding to the expansion of the bottom of upper esophageal ("pouch sign")
      increases the specificity of diagnosis. However, prenatal diagnosis remains
      difficult and less than 50 % of EA are diagnosed prenatally. Biochemical analysis
      could improve these results. If EA is confirmed at birth, surgical management
      consists in a primary end-to-end anastomosis in first days of life, or in two
      steps surgery if the defect is too large. Although current prognosis of EA is
      good, frequency of surgical complications and esophageal lesions secondary to
      gastroesophageal reflux justify a systematic and multidisciplinary extended
      follow-up.

PMID- 24440127
TI  - [Off-label use of misoprostol in obstetrics and gynecology: methods and
      organization].

PMID- 24440128
TI  - [Pregnancy, delivery and customs: transcultural approach in obstetrics].
AB  - Pregnancy and delivery are at the heart of all cultures and ethnic groups, as
      they assure the continuity of any community. Over the millennia, each society has
      elaborated a combination of prescriptions, proscriptions and protective rites for
      future mothers and babies, based on their observations of nature in combination
      with their religious and mythic convictions. Common to the majority are the
      vulnerability of the mother-to-be to spirits, and the crucial and symbolic
      importance of the placenta and the umbilical cord. Delivery in hospital, in spite
      of its reassurance of greater security, may be an unpleasant experience (to both
      mother and family) because of the impossibility of respecting traditions. Medical
      personnel in charge of such culturally uprooted patients should, with the help of
      cultural mediators, become familiar with a minimum of customs and taboos (of the
      patient's community) and win the patient's confidence through a respectful
      approach and an empathetic listening in order to adapt their necessary practices
      of hygiene and security.

PMID- 24440129
TI  - [Surgical treatment of clitoral cysts complicating female genital mutilation].
AB  - We report the surgical management of eight vulvar tumors occurred at the waning
      of female genital mutilation practiced in childhood. Patients were aged 19 to 38
      years. It was essentially excision type 2. Surgical excision of the labia minora
      with a refund without clitoral plasty gave satisfactory aesthetic and functional
      results. Histological examination of these tumors showed a single cyst containing
      keratin without inflammatory reaction.

PMID- 24440130
TI  - [Hyperemesis gravidarum and pregnancy outcomes].
AB  - OBJECTIVES: The aim of this study was to determine the impact of hyperemesis
      gravidarum (HG) on pregnancy. METHODS: For this purpose, we conducted a
      retrospective cohort study between January 1st, 2006 and July 31st, 2009 in the
      level-3 maternity of the South Reunion teaching hospital, Saint-Pierre. Perinatal
      outcomes (gestational diabetes mellitus, hypertensive disorders of pregnancy,
      caesarean section, IUGR<10th percentile, low birth weight<2500 g, preterm
      birth<37 weeks, perinatal death) were compared among the women hospitalized for
      HG (exposed group) and a non-exposed group randomly selected from the South
      Reunion birth register. Finally, we also investigated the interactions between HG
      and maternal weight gain to assess whether HG might change perinatal outcomes
      according to weight gain. RESULTS: During the study period, 215 women
      hospitalized for HG delivered (cumulative incidence rate of HG 14.10/00 among
      total deliveries), of which 197 were included in the exposed group. The low
      gestational weight gain (<7 kg), used as a criterion to define severe HG, was
      significantly more likely in the exposed group (30.5% versus 16.1%, P<0.0001).
      There was no significant association between HG and the various perinatal
      outcomes tested. The risk of delivering a low birth weight neonate was twofold
      (adjusted RR: 2.0, 95%CI: 1.0-3.1), that for a small-for-gestational age infant
      was more likely (adjusted RR: 1.7, 95% CI: 1.1-2.4), both only in case of severe
      HG. CONCLUSION: Severe HG, defined for women with a gestational weight gain of
      less than 7 kg, is a poor prognostic factor for fetal growth.

PMID- 24440131
TI  - [Pharmacology of misoprostol (pharmacokinetic data, adverse effects and
      teratogenic effects)].
AB  - Misoprostol is a synthetic analogue of prostaglandin E1. It is used in
      gynaecology because of its properties of myometrium smooth muscle cells
      contraction and its effects on the cervix. Misoprostol oral bioavailability is
      low and several authors have assessed whether the administration by other routes
      increased its pharmacodynamic effects. This paper summarizes the pharmacokinetic
      studies after other routes of administration: vaginal, sublingual, buccal or
      rectal. It also provides an update on its adverse effects and teratogenic
      effects. 

PMID- 24440132
TI  - Experiment and hydro-mechanical coupling simulation study on the human
      periodontal ligament.
AB  - In this paper, a new method involving an experiment in vivo and hydro-mechanical
      coupling simulations was proposed to investigate the biomechanical property of
      human periodontal ligament (PDL). Teeth were loaded and their displacements were
      measured in vivo. The finite element model of the experiment was built and hydro
      mechanical coupling simulations were conducted to test some PDL's constitutive
      models. In the simulations, the linear elastic model, the hyperfoam model, and
      the Ogden model were assumed for the solid phase of the PDL coupled with a model
      of the fluid phase of the PDL. The displacements of the teeth derived from the
      simulations were compared with the experimental data to validate these
      constitutive models. The study shows that a proposed constitutive model of the
      PDL can be reliably tested by this method. Furthermore, the influence of species,
      areas, and the fluid volume ratio on PDL's mechanical property should be
      considered in the modeling and simulation of the mechanical property of the PDL. 

PMID- 24440133
TI  - A novel method for pulmonary embolism detection in CTA images.
AB  - In this paper, we propose a new computer-aided detection (CAD) - based method to
      detect pulmonary embolism (PE) in computed tomography angiography images (CTAI).
      Since lung vessel segmentation is the main objective to provide high sensitivity
      in PE detection, this method performs accurate lung vessel segmentation. To
      concatenate clogged vessels due to PEs, the starting region of PEs and some
      reference points (RPs) are determined. These RPs are detected according to the
      fixed anatomical structures. After lung vessel tree is segmented, the region,
      intensity, and size of PEs are used to distinguish them. We used the data sets
      that have heart disease or abnormal tissues because of lung disease except PE in
      this work. According to the results, 428 of 450 PEs, labeled by the radiologists
      from 33 patients, have been detected. The sensitivity of the developed system is
      95.1% at 14.4 false positive per data set (FP/ds). With this performance, the
      proposed CAD system is found quite useful to use as a second reader by the
      radiologists. 

PMID- 24440134
TI  - Direct volume manipulation for visualizing intraoperative liver resection
      process.
AB  - This paper introduces a new design and application for direct volume manipulation
      for visualizing the intraoperative liver resection process. So far, interactive
      volume deformation and resection have been independently handled due to the
      difficulty of representing elastic behavior of volumetric objects. Our framework
      models global shape editing and discontinuous local deformation by merging proxy
      geometry encoding and displacement mapping. A local-frame-based elastic model is
      presented to allow stable editing of the liver shape including bending and
      twisting while preserving the volume. Several tests using clinical CT data have
      confirmed the developed software and interface can represent the intraoperative
      state of liver and produce local views of reference vascular structures, which
      provides a "road map of vessels" that are key features when approaching occluded
      tumors during surgery. 

PMID- 24440135
TI  - Modified CC-LR algorithm with three diverse feature sets for motor imagery tasks
      classification in EEG based brain-computer interface.
AB  - Motor imagery (MI) tasks classification provides an important basis for designing
      brain-computer interface (BCI) systems. If the MI tasks are reliably
      distinguished through identifying typical patterns in electroencephalography
      (EEG) data, a motor disabled people could communicate with a device by composing
      sequences of these mental states. In our earlier study, we developed a cross
      correlation based logistic regression (CC-LR) algorithm for the classification of
      MI tasks for BCI applications, but its performance was not satisfactory. This
      study develops a modified version of the CC-LR algorithm exploring a suitable
      feature set that can improve the performance. The modified CC-LR algorithm uses
      the C3 electrode channel (in the international 10-20 system) as a reference
      channel for the cross-correlation (CC) technique and applies three diverse
      feature sets separately, as the input to the logistic regression (LR) classifier.
      The present algorithm investigates which feature set is the best to characterize
      the distribution of MI tasks based EEG data. This study also provides an insight
      into how to select a reference channel for the CC technique with EEG signals
      considering the anatomical structure of the human brain. The proposed algorithm
      is compared with eight of the most recently reported well-known methods including
      the BCI III Winner algorithm. The findings of this study indicate that the
      modified CC-LR algorithm has potential to improve the identification performance
      of MI tasks in BCI systems. The results demonstrate that the proposed technique
      provides a classification improvement over the existing methods tested. 

PMID- 24440136
TI  - Effects of virtual environment platforms on emotional responses.
AB  - The goal of the current study was to investigate the effects of different virtual
      environment (VE) technologies (i.e., desktop, head mounted display, or fully
      immersive platforms) on emotional arousal and task performance. Fifty-three
      participants were recruited from a college population. Reactivity to stressful
      VEs was examined in three VE systems from desktop to high-end fully immersive
      systems. The experiment was a 3 (desktop system, head mounted display, and six
      wall system)*2 (high- and low-stressful VE) within subject design, with self
      reported emotional arousal and valence, skin conductance, task performance,
      presence, and simulator sickness examined as dependent variables. Replicating
      previous studies, the fully immersive system induced the highest sense of
      presence and the head mounted display system elicited the highest amount of
      simulator sickness. Extending previous studies, the results demonstrated that VE
      platforms were associated with different patterns in emotional responses and task
      performance. Our findings suggest that different VE systems may be appropriate
      for different scientific purposes when studying stress reactivity using
      emotionally evocative tasks. 

PMID- 24440137
TI  - Prenatal diagnosis: the irresistible rise of the 'visible fetus'.
AB  - Prenatal diagnosis was developed in the 1970s, a result of a partly contingent
      coming together of three medical innovations-amniocentesis, the study of human
      chromosomes and obstetrical ultrasound-with a social innovation, the
      decriminalization of abortion. Initially this diagnostic approach was proposed
      only to women at high risk of fetal malformations. Later, however, the
      supervision of the fetus was extended to all pregnant women. The latter step was
      strongly favoured by professionals' aspiration to prevent the birth of children
      with Down syndrome, an inborn condition perceived as a source of suffering for
      families and a burden on public purse. Experts who promoted screening for 'Down
      risk' assumed that the majority of women who carry a Down fetus will decide to
      terminate the pregnancy, and will provide a private solution to a public health
      problem. The generalization of screening for Down risk increased in turn the
      frequency of diagnoses of other, confirmed or potential fetal pathologies, and of
      dilemmas linked with such diagnoses. Debates on such dilemmas are usually limited
      to professionals. The transformation of prenatal diagnosis into a routine medical
      technology was, to a great extent, an invisible revolution. 

PMID- 24440138
TI  - Bisphosphonate-related osteonecrosis of the jaws of dental origin.

PMID- 24440139
TI  - The proinflammatory effect of C-reactive protein on human endothelial cells
      depends on the FcgammaRIIa genotype.
AB  - INTRODUCTION: The stimulatory effects of CRP (C-reactive protein) on endothelial
      cells are mainly mediated via FcgammaRIIa. This receptor exists in two different
      allotypes bearing either arginine (R131) or histidine (H131) at the extracellular
      amino acid position 131 of the mature protein, but only FcgammaRIIa-R131 displays
      high avidity for CRP. This study investigated the role of the FcgammaRIIa
      genotype in CRP-stimulated endothelial cells. MATERIALS AND METHODS: We tested
      the effects of CRP on expression of the adhesion molecules ICAM-1, VCAM-1, and E
      selectin, as well as the endothelial release of pro-inflammatory molecules as a
      function of the FcgammaRIIa-genotype (FcgammaRIIa-H/H131, FcgammaRIIa-H/R131,
      FcgammaRIIa-R/R131) in HUVEC (Human Umbilical Vein Endothelial Cells). HUVEC were
      grouped according to their FcgammaRIIa status by genotyping with an allele
      specific nested-PCR. The expression of ICAM-1, VCAM-1, and E-selectin on HUVEC
      was detected by flow cytometry. The release of soluble markers (sCD40L, IL-6, IL
      8, MCP-1, tPA, sP-selectin, and sVCAM-1) was measured using a multiplex assay for
      flow cytometry. RESULTS AND CONCLUSIONS: CRP-stimulated expression of ICAM-1 and
      E-selectin was dependent on the specific FcgammaRIIa-genotype, with most
      pronounced induction in HUVEC with the FcgammaRIIa-R/R genotype, followed by H/R
      and H/H. In accordance with this finding, the supernatants of stimulated HUVEC
      with the R/R genotype showed significantly higher levels of tPA, MCP-1, and IL-6.
      Our data show that CRP stimulates the expression of adhesion molecules and the
      release of soluble markers by HUVEC as a function of the FcgammaRIIa-genotype.
      These findings could be relevant in the context of risk stratification in
      patients with cardiovascular disease.

PMID- 24440140
TI  - The platelet and the biophysical microenvironment: lessons from cellular
      mechanics.
AB  - While the role of platelets in hemostasis is well characterized from a biological
      perspective, the biophysical interactions between platelets and their mechanical
      microenvironment are relatively unstudied. The field of cellular mechanics has
      developed a number of approaches to study the effects of extracellular matrix
      (ECM)-derived mechanical forces on various cells, and has elucidated that
      integrin-cytoskeleton-mediated force transduction governs many cellular
      processes. As platelets adhere and spread via molecular machinery that is similar
      to that which enables other cells to mechanosense and mechanotransduce forces
      from their biophysical microenvironment, platelets too are likely governed by the
      same overarching mechanisms. Indeed, recent platelet mechanobiology studies have
      revealed that key aspects of platelet physiology and activation are regulated by
      the mechanical and spatial properties of the ECM microenvironment. At the same
      time, there are also key differences that make platelets unique in the world of
      cells-- their size, origin as megakaryocyte fragments, and unique alphaIIbbeta3
      integrin-- render their mechanosensing activities particularly interesting. The
      structurally "simple," anucleate nature of platelets coupled with their high
      actin concentration (20% of total protein) and integrin density [1] seem to make
      them ideal for mechanical force generation and transmission. Further studies will
      enhance our understanding of the role of platelet mechanobiology in hemostasis
      and thrombosis, potentially leading to new categories of diagnostics that
      investigate the mechanical properties of clots to determine bleeding risk, as
      well as therapies that target the mechanotransduction signaling pathway to alter
      the stability of clots. 

PMID- 24440141
TI  - Post-marketing surveillance of thrombomodulin alfa, a novel treatment of
      disseminated intravascular coagulation - safety and efficacy in 1,032 patients
      with hematologic malignancy.
AB  - INTRODUCTION: Post-marketing surveillance of thrombomodulin alfa (TM-alpha) was
      performed to evaluate safety and efficacy in patients with disseminated
      intravascular coagulation (DIC) with hematologic malignancy. MATERIALS AND
      METHODS: All patients treated with TM-alpha from May 2008 to April 2010 in Japan
      were included. Information about baseline characteristics, safety, and efficacy
      were collected. The DIC resolution rate, survival rate on Day 28 after the last
      TM-alpha administration, and changes in DIC score and coagulation tests were
      evaluated. RESULTS: The underlying diseases associated with DIC were acute
      myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma
      (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia
      (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates
      of bleeding-related adverse events and adverse drug reactions were 17.8% and
      4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were
      assessed as disappeared or improved based on symptoms after TM-alpha treatment.
      The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC
      score and coagulation tests including thrombin-antithrombin complex (TAT) were
      significantly improved. Coagulation tests were significantly improved after TM
      alpha treatment even in subjects whose clinical course of underlying disease was
      assessed as unchanged or exacerbated. CONCLUSIONS: This surveillance confirmed
      the safety and efficacy of TM-alpha in clinical practice, thus TM-alpha may be an
      ideal treatment for patients with DIC based upon hematologic malignancy.

PMID- 24440142
TI  - Impact of CYP2C19 polymorphism and proton pump inhibitors on platelet reactivity
      to clopidogrel and clinical outcomes following stent implantation.
AB  - BACKGROUND: The response to clopidogrel, and some kind of the drug interaction
      are multifactorial. METHODS AND RESULTS: We enrolled 174 consecutive patients and
      determined CYP2C19 genotypes, measured platelet aggregation, and assessed the
      relationship between CYP2C19 genotype and platelet reactivity 24hours after
      clopidogrel administration, and the risk of cardiovascular events over 18months
      follow-up. A sub analysis examined the impact of rabeprazole, a proton pump
      inhibitor (PPI) less affected by CYP2C19. The CYP2C19 genotype was extensive
      metabolizer (EM) in 36%, intermediate metabolizer (IM) in 45%, and poor
      metabolizer (PM) in 19%. Platelet reactivity was significantly lower in the EM
      group than in the IM and PM groups (EM, IM, PM: 3560+/-1404, 4203+/-1302, 5084+/
      1007AU*min, P<0.05). The cardiovascular event rate was higher in the IM and PM
      groups than in the EM group (12.7% and 12.5% vs 1.6%; Hazard ratio for IM 10.6,
      P=0.029; for PM 11.3, P=0.040). No differences were seen between patients taking
      (N=50) and not taking (N=124) rabeprazole in residual platelet aggregation
      (4407+/-1360 vs 4048+/-1394, AU*min, P=0.2782), or in cardiovascular events
      (10.0% vs 8.1%, HR 0.97, P=0.97). CONCLUSIONS: CYP2C19 genotype is associated
      with an increased risk of cardiovascular events following stent implantation in
      Japanese patients.

PMID- 24440143
TI  - Calorie restriction dose-dependently abates lipopolysaccharide-induced fever,
      sickness behavior, and circulating interleukin-6 while increasing corticosterone.
AB  - In mice a 50% calorie restriction (CR) for 28days attenuates sickness behavior
      after lipopolysaccharide (LPS) and these mice demonstrate a central anti
      inflammatory bias. This study examined the dose-dependent effect of CR on
      sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post
      LPS. Male Sprague-Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28days
      were injected on day 15, 22, or 29 with 50MUg/kg of LPS or saline (1mL/500g).
      Changes in body temperature (Tb), locomotor activity, body weight, and food
      intake were determined. A separate cohort of rats was fed ad libitum or CR by 50%
      for 28days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and
      IL-10 were determined at 0, 2, and 4h post-LPS. The rats CR for 28days
      demonstrated the largest attenuation of sickness behavior: no fever, limited
      reduction in locomotor activity, no anorexia, and reduced cachexia following LPS.
      Rats CR for 14 and 21days demonstrated a partial attenuation of sickness
      behavior. Rats CR for 14days demonstrated a larger increase in Tb, larger
      reduction in locomotor activity, and larger weight loss compared to rats CR for
      21days. Serum CORT was increased at 2h post-LPS in ad libitum and CR groups;
      however it was two times larger in the CR animals. Levels of IL-6 were
      significantly attenuated at 2h post-LPS in the CR animals. IL-10 levels were
      similar post-LPS. CR results in an enhanced anti-inflammatory response in the
      form of increased CORT and diminished pro-inflammatory signals. 

PMID- 24440144
TI  - The sympathetic nervous system modulates CD4(+)Foxp3(+) regulatory T cells via
      noradrenaline-dependent apoptosis in a murine model of lymphoproliferative
      disease.
AB  - The sympathetic nervous system (SNS) plays a crucial role in the course and
      development of autoimmune disease in Fas-deficient lpr/lpr mice. As regulatory T
      cells (Tregs) are considered important modulators of autoimmune processes, we
      analyzed the interaction between the SNS and Tregs in this murine model of
      lymphoproliferative disease. We found that the percentage of Tregs among CD4(+) T
      cells is increased in the spleen, lymph nodes, and thymus of lpr/lpr mice as
      compared to age-matched C57Bl/6J (B6) mice. Furthermore, noradrenaline (NA), the
      main sympathetic neurotransmitter, induced apoptosis in B6- and lpr/lpr-derived
      Tregs. NA also reduced the frequency of Foxp3(+) cells and Foxp3 mRNA expression
      via beta2-adrenoceptor (beta2-AR)-mediated mechanisms in a concentration and time
      dependent manner. Destruction of peripheral sympathetic nerves by 6
      hydroxydopamine significantly increased the percentage of Tregs in B6 control
      mice to an extent comparable to aged-matched lpr/lpr mice. The concentration of
      splenic NA negatively correlated with the frequency of CD4(+)Foxp3(+) Tregs.
      Additionally, 60days after sympathectomy, a partial recovery of NA concentrations
      led to Treg percentages comparable to those of intact, vehicle-treated controls.
      Immunohistochemical analysis of the spleen revealed localization of single
      Foxp3(+) Tregs in proximity to NA-producing nerve fibers, providing an interface
      between Tregs and the SNS. Taken together, our data suggest a relation between
      the degree of splenic sympathetic innervation and the size of the Treg
      compartment. While there are few examples of endogenous substances capable of
      affecting Tregs, our results provide a possible explanation of how the magnitude
      of the Treg compartment in the spleen can be regulated by the SNS. 

PMID- 24440145
TI  - Next generation sequencing and its application in deciphering head and neck
      cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) are a group of heterogeneous
      tumours mainly attributable to tobacco use, alcohol consumption and infection
      with human papillomavirus. Based on the stage of cancer at the time of diagnosis,
      patients are managed by surgery, radiotherapy, chemotherapy or a combination of
      these. Early diagnosis usually improves patient prognosis. Since their first
      commercial application in 2005, next generation sequencing (NGS) platforms are
      rapidly changing the face of basic science laboratories; however prior to
      progressing to clinical applications, clinicians should carefully examine
      currently available data and guidelines for technical and ethical matters
      concerning NGS. In this review, we compare various commercially available NGS
      platforms, with special consideration given to their clinical application in the
      management of HNSCC. 

PMID- 24440146
TI  - Application of circulating plasma/serum EBV DNA in the clinical management of
      nasopharyngeal carcinoma.
AB  - Elevated levels of circulating cell-free Epstein-Barr virus (EBV) DNA have been
      detected in plasma and serum samples from nasopharyngeal cancer (NPC) patients by
      quantitative real time PCR (qPCR) test. This qPCR test for circulating EBV DNA
      was found to be useful in the clinical management of NPC patients. For instance,
      EBV DNA qPCR test has good sensitivity and specificity in the detection of NPC at
      disease onset. Increase of the viral DNA load was found in NPC patients at late
      stages of disease. High EBV DNA load at disease onset or detectable viral load
      post-treatment was associated with poor survival or frequent relapse in NPC
      patients. Residual EBV DNA load after primary treatment could be a useful
      indicator to justify adjuvant chemotherapy. The qPCR test might also be applied
      to define a poor prognostic group in patients at early stage (I/II) for
      implementing concurrent chemo-radiotherapy (chemo-RT) to improve patients'
      outcome. The test is also useful to monitor distant metastases or response to
      radiotherapy, chemo-RT or surgery. Supplementary tests, however, are needed to
      pick up EBV negative WHO type I NPC and test improvement is needed to increase
      sensitivity in detecting stage I disease and local recurrence. 

PMID- 24440147
TI  - Diagnosis and classification of celiac disease and gluten sensitivity.
AB  - Celiac disease is a complex disorder, the development of which is controlled by a
      combination of genetic (HLA alleles) and environmental (gluten ingestion)
      factors. New diagnostic guidelines developed by ESPGHAN emphasize the crucial
      role of serological tests in the diagnostic process of symptomatic subjects, and
      of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic
      subjects belonging to at-risk groups. The serological diagnosis of CD is based on
      the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti
      endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti
      deamidated gliadin peptide antibody assays of the IgG class are used. When anti
      tTG antibody levels are very high, antibody specificity is absolute and CD can be
      diagnosed without performing a duodenum biopsy. Non-celiac gluten sensitivity is
      a gluten reaction in which both allergic and autoimmune mechanisms have been
      ruled out. Diagnostic criteria include the presence of symptoms similar to those
      of celiac or allergic patients; negative allergological tests and absence of anti
      tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of
      the symptoms with a gluten-free diet; relapse of the symptoms when gluten is
      reintroduced. 

PMID- 24440148
TI  - A case study of the Secure Anonymous Information Linkage (SAIL) Gateway: a
      privacy-protecting remote access system for health-related research and
      evaluation.
AB  - With the current expansion of data linkage research, the challenge is to find the
      balance between preserving the privacy of person-level data whilst making these
      data accessible for use to their full potential. We describe a privacy-protecting
      safe haven and secure remote access system, referred to as the Secure Anonymised
      Information Linkage (SAIL) Gateway. The Gateway provides data users with a
      familiar Windows interface and their usual toolsets to access approved
      anonymously-linked datasets for research and evaluation. We outline the
      principles and operating model of the Gateway, the features provided to users
      within the secure environment, and how we are approaching the challenges of
      making data safely accessible to increasing numbers of research users. The
      Gateway represents a powerful analytical environment and has been designed to be
      scalable and adaptable to meet the needs of the rapidly growing data linkage
      community. 

PMID- 24440149
TI  - Costimulatory molecule DNAM-1 is essential for optimal differentiation of memory
      natural killer cells during mouse cytomegalovirus infection.
AB  - Recent studies demonstrate that natural killer (NK) cells have adaptive immune
      features. Here, we investigated the role of the costimulatory molecule DNAM-1 in
      the differentiation of NK cells in a mouse model of cytomegalovirus (MCMV)
      infection. Antibody blockade of DNAM-1 suppressed the expansion of MCMV-specific
      Ly49H(+) cells during viral infection and inhibited the generation of memory NK
      cells. Similarly, DNAM-1-deficient (Cd226(-/-)) Ly49H(+) NK cells exhibited
      intrinsic defects in expansion and differentiation into memory cells. Src-family
      tyrosine kinase Fyn and serine-threonine protein kinase C isoform eta (PKCeta)
      signaling through DNAM-1 played distinct roles in the generation of MCMV-specific
      effector and memory NK cells. Thus, cooperative signaling through DNAM-1 and
      Ly49H are required for NK cell-mediated host defense against MCMV infection. 

PMID- 24440150
TI  - Tuning of antigen sensitivity by T cell receptor-dependent negative feedback
      controls T cell effector function in inflamed tissues.
AB  - Activated T cells must mediate effector responses sufficiently to clear pathogens
      while avoiding excessive tissue damage. Here we have combined dynamic intravital
      microscopy with ex vivo assessments of T cell cytokine responses to generate a
      detailed spatiotemporal picture of CD4(+) T cell effector regulation in the skin.
      In response to antigen, effector T cells arrested transiently on antigen
      presenting cells, briefly producing cytokine and then resuming migration. Antigen
      recognition led to upregulation of the programmed death-1 (PD-1) glycoprotein by
      T cells and blocking its canonical ligand, programmed death-ligand 1 (PD-L1),
      lengthened the duration of migration arrest and cytokine production, showing that
      PD-1 interaction with PD-L1 is a major negative feedback regulator of antigen
      responsiveness. We speculate that the immune system employs T cell recruitment,
      transient activation, and rapid desensitization to allow the T cell response to
      rapidly adjust to changes in antigen presentation and minimize collateral injury
      to the host.

PMID- 24440152
TI  - A survey of ancient conserved non-coding elements in the PAX6 locus reveals a
      landscape of interdigitated cis-regulatory archipelagos.
AB  - Biological differences between cell types and developmental processes are
      characterised by differences in gene expression profiles. Gene-distal enhancers
      are key components of the regulatory networks that specify the tissue-specific
      expression patterns driving embryonic development and cell fate decisions, and
      variations in their sequences are a major contributor to genetic disease and
      disease susceptibility. Despite advances in the methods for discovery of putative
      cis-regulatory sequences, characterisation of their spatio-temporal enhancer
      activities in a mammalian model system remains a major bottle-neck. We employed a
      strategy that combines gnathostome sequence conservation with transgenic mouse
      and zebrafish reporter assays to survey the genomic locus of the developmental
      control gene PAX6 for the presence of novel cis-regulatory elements. Sequence
      comparison between human and the cartilaginous elephant shark (Callorhinchus
      milii) revealed several ancient gnathostome conserved non-coding elements
      (agCNEs) dispersed widely throughout the PAX6 locus, extending the range of the
      known PAX6 cis-regulatory landscape to contain the full upstream PAX6-RCN1
      intergenic region. Our data indicates that ancient conserved regulatory sequences
      can be tested effectively in transgenic zebrafish even when not conserved in
      zebrafish themselves. The strategy also allows efficient dissection of compound
      regulatory regions previously assessed in transgenic mice. Remarkable overlap in
      expression patterns driven by sets of agCNEs indicates that PAX6 resides in a
      landscape of multiple tissue-specific regulatory archipelagos. 

PMID- 24440151
TI  - A potential molecular pathogenesis of cardiac/laterality defects in Oculo-Facio
      Cardio-Dental syndrome.
AB  - Pitx2 is the last effector of the left-right (LR) cascade known to date and plays
      a crucial role in the patterning of LR asymmetry. In Xenopus embryos, the
      expression of Pitx2 gene in the left lateral plate mesoderm (LPM) is directly
      regulated by Xnr1 signaling, which is mediated by Smads and FoxH1. Previous
      studies suggest that the suppression of Pitx2 gene in the left LPM is a potential
      cause of cardiac/laterality defects in Oculo-Facio-Cardio-Dental (OFCD) syndrome,
      which is known to be caused by mutations in BCL6 co-repressor (BCOR) gene.
      Recently, our work has revealed that the BCL6/BCOR complex blocks Notch-dependent
      transcriptional activity to protect the expression of Pitx2 in the left LPM from
      the inhibitory activity of Notch signaling. These studies indicated that
      uncontrolled Notch activity in the left LPM caused by dysfunction of BCOR may
      result in cardiac/laterality defects of OFCD syndrome. However, this Notch
      dependent inhibitory mechanism of Pitx2 gene transcription still remains unknown.
      Here we report that transcriptional repressor ESR1, which acts downstream of
      Notch signaling, inhibits the expression of Pitx2 gene by binding to a left side
      specific enhancer (ASE) region in Pitx2 gene and recruiting histone deacetylase 1
      (HDAC1) to this region. Once HDAC1 is tethered, histone acetyltransferase p300 is
      no longer recruited to the Xnr1-dependent transcriptional complex on the ASE
      region, leading to the suppression of Pitx2 gene in the left LPM. The study
      presented here uncovers the regulatory mechanism of Pitx2 gene transcription
      which may contribute to an understanding of pathogenesis of OFCD syndrome.

PMID- 24440153
TI  - EHD1 mediates vesicle trafficking required for normal muscle growth and
      transverse tubule development.
AB  - EHD proteins have been implicated in intracellular trafficking, especially
      endocytic recycling, where they mediate receptor and lipid recycling back to the
      plasma membrane. Additionally, EHDs help regulate cytoskeletal reorganization and
      induce tubule formation. It was previously shown that EHD proteins bind directly
      to the C2 domains in myoferlin, a protein that regulates myoblast fusion. Loss of
      myoferlin impairs normal myoblast fusion leading to smaller muscles in vivo but
      the intracellular pathways perturbed by loss of myoferlin function are not well
      known. We now characterized muscle development in EHD1-null mice. EHD1-null
      myoblasts display defective receptor recycling and mislocalization of key muscle
      proteins, including caveolin-3 and Fer1L5, a related ferlin protein homologous to
      myoferlin. Additionally, EHD1-null myoblast fusion is reduced. We found that loss
      of EHD1 leads to smaller muscles and myofibers in vivo. In wildtype skeletal
      muscle EHD1 localizes to the transverse tubule (T-tubule), and loss of EHD1
      results in overgrowth of T-tubules with excess vesicle accumulation in skeletal
      muscle. We provide evidence that tubule formation in myoblasts relies on a
      functional EHD1 ATPase domain. Moreover, we extended our studies to show EHD1
      regulates BIN1 induced tubule formation. These data, taken together and with the
      known interaction between EHD and ferlin proteins, suggests that the EHD proteins
      coordinate growth and development likely through mediating vesicle recycling and
      the ability to reorganize the cytoskeleton. 

PMID- 24440154
TI  - Mdm2 is required for maintenance of the nephrogenic niche.
AB  - The balance between nephron progenitor cell (NPC) renewal, survival and
      differentiation ultimately determines nephron endowment and thus susceptibile to
      chronic kidney disease and hypertension. Embryos lacking the p53-E3 ubiquitin
      ligase, Murine double minute 2 (Mdm2), die secondary to p53-mediated apoptosis
      and growth arrest, demonstrating the absolute requirement of Mdm2 in
      embryogenesis. Although Mdm2 is required in the maintenance of hematopoietic stem
      cells, its role in renewal and differentiation of stem/progenitor cells during
      kidney organogenesis is not well defined. Here we examine the role of the Mdm2
      p53 pathway in NPC renewal and fate in mice. The Six2-GFP::Cre(tg/+) mediated
      inactivation of Mdm2 in the NPC (NPC(Mdm)2(-/-)) results in perinatal lethality.
      NPC(Mdm)2(-/-) neonates have hypo-dysplastic kidneys, patchy depletion of the
      nephrogenic zone and pockets of superficially placed, ectopic, well
      differentiated proximal tubules. NPC(Mdm2-/-) metanephroi exhibit thinning of the
      progenitor GFP(+)/Six2(+) population and a marked reduction or loss of progenitor
      markers Amphiphysin, Cited1, Sall1 and Pax2. This is accompanied by aberrant
      accumulation of phospho-gammaH2AX and p53, and elevated apoptosis together with
      reduced cell proliferation. E13.5-E15.5 NPC(Mdm2-/-) kidneys show reduced
      expression of Eya1, Pax2 and Bmp7 while the few surviving nephron precursors
      maintain expression of Wnt4, Lhx1, Pax2, and Pax8. Lineage fate analysis and
      section immunofluorescence revealed that NPC(Mdm2-/-) kidneys have severely
      reduced renal parenchyma embedded in an expanded stroma. Six2-GFP::Cre(tg/+);
      Mdm2(f/f) mice bred into a p53 null background ensures survival of the GFP
      positive, self-renewing progenitor mesenchyme and therefore restores normal renal
      development and postnatal survival of mice. In conclusion, the Mdm2-p53 pathway
      is essential to the maintenance of the nephron progenitor niche.

PMID- 24440156
TI  - Anti-interleukin-6 receptor antibody (MR16-1) promotes muscle regeneration via
      modulation of gene expressions in infiltrated macrophages.
AB  - BACKGROUND: Although rat anti-mouse IL-6 receptor (IL-6R) antibody (MR16-1) has
      been reported to effectively ameliorate various tissue damages, its effect on
      skeletal muscle regeneration has not been determined. Moreover, the localization,
      persistence and duration of action of this reagent in damaged tissues after
      systemic administration have not been assessed. METHODS: The MR16-1 was
      administered i.p. immediately after cardiotoxin (CTX)-induced muscle damage on
      mice. RESULTS: MR16-1 administered i.p. was observed only to the damaged muscle.
      This delivered MR16-1 was dramatically decreased from 3 to 7days post-injury
      concomitantly with a reduction of IL-6R expression. This reduction of the MR16-1
      level in the damaged muscle was not rescued by additional administration of MR16
      1, suggesting the short half-life of MR16-1 was not the factor for the remaining
      levels. In addition, a significant inhibitory effect of MR16-1 on phosphorylation
      of the signal transducer and activator of transcription 3 was observed in the
      macrophage-enriched area of damaged muscle 3days after injury. Finally, the
      acceleration of muscle regeneration observed at day 7 post-injury following MR16
      1 treatment was associated with reduced expression of fibrosis-related genes,
      such as interleukin-10 and arginase, in the infiltrated macrophages. CONCLUSIONS:
      These results suggest that MR16-1 which was found primarily localized in
      infiltrated macrophages in the damaged muscle might facilitate muscle
      regeneration via immune modulation. GENERAL SIGNIFICANCE: These findings are
      deemed to provide further insight into the understanding not only of MR16-1
      treatment on muscle regeneration, but also of the other anti-cytokine treatment
      on the cytokine-related disease.

PMID- 24440155
TI  - Thrombospondin-2 and extracellular matrix assembly.
AB  - BACKGROUND: Numerous proteins and small leucine-rich proteoglycans (SLRPs) make
      up the composition of the extracellular matrix (ECM). Assembly of individual
      fibrillar components in the ECM, such as collagen, elastin, and fibronectin, is
      understood at the molecular level. In contrast, the incorporation of non
      fibrillar components and their functions in the ECM are not fully understood.
      SCOPE OF REVIEW: This review will focus on the role of the matricellular protein
      thrombospondin (TSP) 2 in ECM assembly. Based on findings in TSP2-null mice and
      in vitro studies, we describe the participation of TSP2 in ECM assembly, cell-ECM
      interactions, and modulation of the levels of matrix metalloproteinases (MMPs).
      MAJOR CONCLUSIONS: Evidence summarized in this review suggests that TSP2 can
      influence collagen fibrillogenesis without being an integral component of
      fibrils. Altered ECM assembly and excessive breakdown of ECM can have both
      positive and negative consequences including increased angiogenesis during tissue
      repair and compromised cardiac tissue integrity, respectively. GENERAL
      SIGNIFICANCE: Proper ECM assembly is critical for maintaining cell functions and
      providing structural support. Lack of TSP2 is associated with increased
      angiogenesis, in part, due to altered endothelial cell-ECM interactions.
      Therefore, minor changes in ECM composition can have profound effects on cell and
      tissue function. This article is part of a Special Issue entitled Matrix-mediated
      cell behaviour and properties.

PMID- 24440157
TI  - Interactions of age and leg muscle fatigue on unobstructed walking and obstacle
      crossing.
AB  - Older adults commonly report muscle fatigue, which may be associated with reduced
      walking ability. Elderly may have insufficient awareness of the balance threat
      caused by muscle fatigue. The aim of this study was to analyze the interaction
      effects of aging and leg muscle fatigue on gait parameters in walking and
      obstacle crossing. One hundred and twenty men, who were divided in six groups
      according to their age (20-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69
      years, above 70 years), participated in this study. Participants performed three
      trials of unobstructed level ground walking and obstacle crossing during walking
      before and after quadriceps muscle fatigue. To induce fatigue, participants
      performed a repeated sit-to-stand task from a chair with arms across the chest to
      a pre-determined cadence (30 cycles/min) using a metronome. Spatial-temporal gait
      parameters (stride length, duration, and speed, step width, and trailing and
      leading heel-clearance) were analyzed, and compared by two-way ANOVA (group and
      fatigue). The results confirmed our hypothesis, showing age-related effects of
      leg muscles fatigue in both gait conditions. From 40 years old, participants
      modulated spatial-temporal and vertical impulses in both tasks more in response
      to fatigue than younger participants, apparently to improve balance and safety.
      Leg muscle fatigue caused age-dependent changes in both unobstructed level ground
      walking and obstacle crossing during walking, which appeared to reflect an
      attempt to maintain balance and safety, probably to counteract adverse fatigue
      effects.

PMID- 24440158
TI  - Household physical activity and mortality in older adults: a national cohort
      study in Spain.
AB  - OBJECTIVE: To examine the association between household physical activity (HPA)
      and all-cause mortality in a cohort of older adults from Spain, and the role of
      sedentary time on this association. METHOD: Prospective cohort study of 2874
      individuals aged >= 62 years. In 2003, the time spent in HPA and the time spent
      seated were self-reported. The association of HPA with all-cause mortality
      through 2011 was assessed with Cox regression. RESULTS: During the follow-up, 970
      participants died. In men, HPA was inversely associated with the risk of death
      only among those with longer sitting time (>= 8 h/d): compared to those who did
      not do HPA, the mortality hazard ratio (HR) was 0.80 (95% confidence interval
      (CI): 0.60-1.08) and 0.43 (95% CI: 0.27-0.69) for those who spent >0 to 2h/d and
      >2h/d in HPA, respectively (P for trend<0.001). In women, sitting time did not
      modify the study association. Thus, compared to women who spent <2h/d in HPA, the
      HR for mortality was 0.72 (95% CI: 0.56-0.93) and 0.52 (95% CI: 0.39-0.70) for
      those who spent >2 to 4h/d, and >4h/d in HPA, respectively (P for trend<0.001).
      CONCLUSION: In women, HPA is associated with reduced mortality regardless of
      sitting time. HPA may also contribute to longer survival among men with longer
      sitting time.

PMID- 24440159
TI  - The influence of free quadrivalent human papillomavirus vaccine (HPV4) on the
      timely completion of the three dose series.
AB  - OBJECTIVE: Economic incentives can positively influence social determinants to
      improve the health care of the uninsured and underserved populations. The aim of
      this study was to determine if free HPV4 vaccine would lead to on-time series
      completion in our safety net health care system in the US Midwest. METHODS: A
      nested retrospective cohort study of females receiving HPV4 vaccine between 2006
      and 2009 was conducted. Patient characteristics and payor source for each of the
      three HPV4 doses were abstracted from electronic records. Logistic regression was
      used to predict on-time completion rates. RESULTS: The proportion of adolescent
      and adult females completing three on-time HPV4 doses was equal (21% (28/136) vs.
      18% (66/358), respectively) from among the 494 females receiving 927 HPV4 doses
      in this study. No adolescent receiving free HPV4 vaccine completed three doses.
      Grant sponsorship of at least one HPV4 dose among adults did not predict three
      dose on-time completion (OR=1.56, 95%CI: 0.80, 3.06). Neither was adult grant
      sponsorship of HPV4 significant when analyzing exclusive payor sources vs. a
      combination of payor sources (OR=0.72, 95%CI: 0.10, 5.17). CONCLUSIONS: Free HPV4
      vaccine does not influence the on-time completion rates among adults.

PMID- 24440160
TI  - Elder abuse and socioeconomic inequalities: a multilevel study in 7 European
      countries.
AB  - OBJECTIVES: To compare the prevalence of elder abuse using a multilevel approach
      that takes into account the characteristics of participants as well as
      socioeconomic indicators at city and country level. METHODS: In 2009, the project
      on abuse of elderly in Europe (ABUEL) was conducted in seven cities (Stuttgart,
      Germany; Ancona, Italy; Kaunas, Lithuania, Stockholm, Sweden; Porto, Portugal;
      Granada, Spain; Athens, Greece) comprising 4467 individuals aged 60-84 years. We
      used a 3-level hierarchical structure of data: 1) characteristics of
      participants; 2) mean of tertiary education of each city; and 3) country
      inequality indicator (Gini coefficient). Multilevel logistic regression was used
      and proportional changes in Intraclass Correlation Coefficient (ICC) were
      inspected to assert explained variance between models. RESULTS: The prevalence of
      elder abuse showed large variations across sites. Adding tertiary education to
      the regression model reduced the country level variance for psychological abuse
      (ICC=3.4%), with no significant decrease in the explained variance for the other
      types of abuse. When the Gini coefficient was considered, the highest drop in ICC
      was observed for financial abuse (from 9.5% to 4.3%). CONCLUSION: There is a
      societal and community level dimension that adds information to individual
      variability in explaining country differences in elder abuse, highlighting
      underlying socioeconomic inequalities leading to such behavior.

PMID- 24440161
TI  - School-based physical activity and nutritional education interventions on body
      mass index: a meta-analysis of randomised community trials - project PANE.
AB  - OBJECTIVE: To evaluate the effect of school-based physical activity (PA) and
      nutritional education (NE) interventions on children's and adolescents' body mass
      index. METHODS: We conducted a systematic search in fourteen databases until
      September 2012 for randomised controlled trials on PA and NE, conducted in the
      school setting, and delivered to children and adolescents. Additionally, we
      performed a cross-reference check in related papers. The title and abstract
      review and the quality assessment were performed by two independent researchers.
      The software EPPI-Reviewer3 was used to store, manage and analyse all data. The
      meta-analysis was conducted using the random-effects model, and the outcomes were
      reported as standardised mean difference (SMD). As a secondary analysis, we
      pooled together the interventions that considered PA or NE alone. RESULTS: Thirty
      eight studies met the eligibility criteria. The main analysis showed a SMD
      between intervention and control groups of -0.03 (95% CI: -0.09, 0.04; n=28,870;
      I(2)=83%). When we considered all 57 trials, there was no difference between the
      results of the primary analysis. CONCLUSION: The synthesis of school-based PA and
      NE interventions showed no statistically significant mean reduction on children's
      and adolescents' body mass index. The high heterogeneity among studies requires
      caution in the generalisation of the results.

PMID- 24440162
TI  - Area-based interventions to ameliorate deprived Dutch neighborhoods in practice:
      does the Dutch District Approach address the social determinants of health to
      such an extent that future health impacts may be expected?
AB  - OBJECTIVE: We studied the local manifestation of a national procedural program
      that addressed problems regarding employment, education, housing and the physical
      neighborhood environment, social cohesion, and safety in the most deprived
      neighborhoods in the Netherlands. We aimed to assess if such a program, without
      the explicit aim to improve health, results in area-based interventions that
      address the social determinants of health to such an extent that future health
      impacts may be expected. METHODS: We used standardized questionnaires and face-to
      face interviews with 39 local district managers. We analyzed the content of the
      area-based interventions to assess if the activities addressed the social
      determinants of health. We assessed the duration and scale of the activities in
      order to estimate their potential to change social determinants of health.
      RESULTS: Most districts addressed all six categories of social determinants of
      health central to the procedural program. Investments in broad-based primary
      schools, housing stock, green space, and social safety seemed to have the
      potential to result in district-level changes in social determinants. The scale
      of activities aimed at employment, income, educational attainment, and the social
      environment seemed too small to expect an impact at the district level.
      CONCLUSION: We conclude that the area-based interventions addressed the
      neighborhood environment to such an extent that future health impacts of the
      Dutch District Approach may be expected. The health effects in the long term
      might be more substantial when area-based interventions were devoted more to the
      improvement of the socioeconomic circumstances of residents.

PMID- 24440163
TI  - Influence of family structure on obesogenic behaviors and placement of bedroom
      TVs of American children: National Survey of Children's Health 2007.
AB  - OBJECTIVE: To explore the relation between family structure and obesogenic
      attributes. METHODS: Publicly available data from the 2007 National Survey of
      Children's Health (n=55,094; 11.6 +/- 0.04 years; 51.2% male) was analyzed in
      fall 2012. Predictor variables included marital status (two-parent biological
      [referent], two-parent blended, single-mother, and other) and number of children.
      Outcome variables included the presence of a bedroom television (BTV), elevated
      television (TV) viewing time, insufficient physical activity, and infrequent
      family meals. RESULTS: Analysis of family structure revealed 63% biological, 11%
      blended, and 20% single-mother families. Twenty-three percent of children did not
      have siblings. When family structure variables were considered independently,
      children in blended (odds ratio (OR): 1.75; 95% confidence interval (CI) 1.45,
      2.10) and single-mother homes (1.49; 1.28, 1.74) had higher odds of BTV. Children
      in blended families had higher odds of elevated TV viewing time (1.28; 1.08,
      1.51). Single-mother homes had higher odds of infrequent family meals (1.28;
      1.07, 1.52). Families with >= 2 children were less likely to have BTV (0.60;
      0.54, 0.66) or elevated TV viewing time (0.74; 0.67, 0.82), and to irregularly
      dine together (0.89; 0.80, 0.99). CONCLUSION: Diverse family structure was
      associated with more obesogenic behaviors and environments. The presence of
      siblings diminished, but did not eliminate, the risk.

PMID- 24440164
TI  - Cloning and expression of hybrid streptokinase towards clot-specific activity.
AB  - Streptokinase (SK) is a thrombolytic agent that is widely used to treat
      myocardial infarction and pulmonary embolism. The lack of fibrin specificity of
      SK for the clot lysis is one of the limitations of SK. In this study, we have
      incorporated the finger and Kringle 2 domains from the human tissue type
      plasminogen activator gene (t-PA) at the 5' end of the SK gene. These domains are
      responsible for specific binding to fibrin. We have used the pRSETB vector in an
      attempt to express the hybrid streptokinase possessing specificity for fibrin. On
      this regard, three hybrid streptokinase were constructed and expressed in
      Escherichia coli BL21 (DE3): the finger domain with SK (FSK), the Kringle 2
      domain with SK (KSK) and the finger domain+Kringle 2 with SK (FKSK). The
      activities of the hybrid SKs were assessed by caseinolytic assay and clot lysis
      assay. All hybrid SKs were found to activate plasminogen in the caseinolytic
      plate assay. In the clot lysis assay, KSK and FSK were able to dissolute human
      blood and artificial clots in a fibrin-dependent manner unlike the SK and FKSK
      proteins. 

PMID- 24440165
TI  - Application of the VPp1 bacteriophage combined with a coupled enzyme system in
      the rapid detection of Vibrio parahaemolyticus.
AB  - For rapid and quantitative detection of Vibrio parahaemolyticus, a method
      combining the specific lysis of bacteriophages with a bacterial luciferase-flavin
      mononucleotide:nicotinamide adenine dinucleotide oxidoreductase bioluminescent
      system in vitro was developed. A V. parahaemolyticus detection system was
      established by optimizing three main influencing factors: bacteriophage titer,
      volume ratio of the bacteriophage to its host bacterium, and lysis time. A
      standard curve between the number of bacteria and the luminescence intensity of
      the coupled enzyme system was studied and revealed a good linear relationship.
      More than 10(7)colony-forming units (cfu).ml(-1) bacteria in pure culture and
      >10(8) cfu.ml(-1) bacteria in oyster samples were readily detected without pre
      enrichment. Furthermore, >10(0) cfu.ml(-1) bacteria in oyster samples were
      readily detected after 4h of enrichment culture. Because of its rapid detection,
      high specificity, and simplicity in operation, this method is an effective tool
      for detecting living bacteria in food and environmental samples.

PMID- 24440166
TI  - Technical challenges of sparing infrahyoid swallowing organs at risk in
      oropharynx squamous cell cancer treated with IMRT.
AB  - This study reports clinical performance in the sparing of infrahyoid swallowing
      organs at risk (SWOARs) in oropharynx cancer intensity-modulated radiation
      therapy (IMRT) plans. Rates of meeting dose-volume planning goals are reported
      and compared with geometry-based estimates of what is achievable. This study also
      develops 3 measures of target-SWOAR geometry and tests their usefulness in
      providing geometry-based dose-volume planning goals. A total of 50 oropharynx
      cancer IMRT plans were reviewed. Success rates in meeting institutional dose
      volume goals were determined for the glottic larynx (G), postcricoid pharynx (P),
      and esophagus (E). The following 3 measures of target-SWOAR geometry were
      investigated as methods of identifying geometry-based planning goals: presence of
      gross disease in neck levels 3 to 4, target-SWOAR overlap, and a 3-dimensional
      (3D) measure of target-SWOAR geometry. Locally advanced disease was predominant
      in this patient population with target volumes overlapping SWOARs in 68% to 98%
      of cases. Clinical rates of success in meeting dose-volume goals varied by SWOAR
      (16% to 82%) but compared well with estimated potentially achievable rates in
      most cases (14% average difference between clinical and potential). Cases grouped
      by the presence of levels 3 to 4 neck nodes or target-SWOAR overlap did not have
      significantly different SWOAR doses. Cases grouped using a 3D measure of target
      SWOAR geometry differed significantly, providing useful geometry-based planning
      goals (e.g., mean Glottis dose <45Gy was achieved 19%, 44%, or 81% of the time in
      each of 3 groups). This study describes the technical challenge of sparing SWOARs
      and investigates several potential methods for grouping cases to assist with
      treatment plan evaluation. Quantifying the 3-D relationship between the targets
      and SWOARs is a promising way of approaching this complex problem. Data presented
      in this paper may be useful to evaluate treatment plans using objective geometry
      based goals. 

PMID- 24440168
TI  - Increasing shape modelling accuracy by adjusting for subject positioning: an
      application to the analysis of radiographic proximal femur symmetry using data
      from the Osteoarthritis Initiative.
AB  - In total hip arthroplasty, the shape of the contra-lateral femur frequently
      serves as a template for preoperative planning. Previous research on contra
      lateral femoral symmetry has been based on conventional hip geometric
      measurements (which reduce shape to a series of linear measurements) and did not
      take the effect of subject positioning on radiographic femur shape into account.
      The aim of this study was to analyse proximal femur symmetry based on statistical
      shape models (SSMs) which quantify global femoral shape while also adjusting for
      differences in subject positioning during image acquisition. We applied our
      recently developed fully automatic shape model matching (FASMM) system to
      automatically segment the proximal femur from AP pelvic radiographs to generate
      SSMs of the proximal femurs of 1258 Caucasian females (mean age: 61.3 SD=9.0). We
      used a combined SSM (capturing the left and right femurs) to identify and adjust
      for shape variation attributable to subject positioning as well as a single SSM
      (including all femurs as left femurs) to analyse proximal femur symmetry. We also
      calculated conventional hip geometric measurements (head diameter, neck width,
      shaft width and neck-shaft angle) using the output of the FASMM system. The
      combined SSM revealed two modes that were clearly attributable to subject
      positioning. The average difference (mean point-to-curve distance) between left
      and right femur shape was 1.0mm before and 0.8mm after adjusting for these two
      modes. The automatic calculation of conventional hip geometric measurements after
      adjustment gave an average absolute percent asymmetry of within 3.1% and an
      average absolute difference of within 1.1mm or 2.9 degrees  for all measurements.
      We conclude that (i) for Caucasian females the global shape of the right and left
      proximal femurs is symmetric without isolated locations of asymmetry; (ii) a
      combined left-right SSM can be used to adjust for radiographic shape variation
      due to subject positioning; and (iii) adjusting for subject positioning increases
      the accuracy of predicting the shape of the contra-lateral hip. 

PMID- 24440170
TI  - A role for diallyl trisulfide in mitochondrial antioxidative stress contributes
      to its protective effects against vascular endothelial impairment.
AB  - Persistent hyperglycemia increases a systemic oxidative stress, causing the onset
      of vascular endothelial dysfunction and atherosclerosis. Diallyl trisulfide
      (DAT), a natural organosulfur compound in garlic, has been reported to have
      actions of dilating blood vessels and antibacteria, etc. In this study, models of
      obese diabetic rat in vivo and high glucose concentration (HG)-induced
      endothelial cell injury in vitro were used to investigate the protective effects
      of DAT on vascular endothelial injury and its underlying mechanisms. In the in
      vivo model, the obese diabetic rats were injected venously with DAT (5.0 mg kg(
      1)d(-1)) and Vitamin E (1.0 mg kg(-1)d(-1)) respectively, once daily for 7
      consecutive days. In the in vitro model, HG-injured HUVEC were treated with or
      without DAT (25 umol L(-1), 50 umol L(-1), 100 umol L(-1)) or Vitamin E (25 umol
      L(-1)) respectively for 24h. The extents of vascular endothelial injury and
      protective effects of DAT were evaluated. The results both in vivo and in vitro
      displayed that DAT-treatment significantly attenuated the endothelial cell
      impairments. Besides, DAT-treatment markedly decreased the levels of
      malondialdehyde (MDA) and reactive oxygen species, whereas elevated the
      activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in
      mitochondrium. Moreover, DAT-treatment considerably improved mitochondrial
      respiration function. Taken together, our results suggest that DAT protects
      vascular endothelium from HG or hyperglycemia induced-injury by reducing
      mitochondrial oxidative stress. The findings provide a novel insight for DAT to
      potentially treat the oxidative stress diseases, i.e., atherosclerosis, diabetes,
      and neurodegenerative diseases.

PMID- 24440171
TI  - Chlormadinone acetate promotes osteoblast differentiation of human mesenchymal
      stem cells through the ERK signaling pathway.
AB  - Bone is continuously remodeled throughout life, and this remodeling is regulated
      by osteoclasts and osteoblasts. Bone-forming osteoblasts are derived from
      mesenchymal stem cells in bone marrow. Here, we have identified a new function of
      chlormadinone acetate (CMA) as an osteogenic activator in human bone marrow
      derived mesenchymal stem cells (hBMSCs). To date, CMA has been used as an oral
      contraceptive and is known to have antiandrogenic activity. Our results show that
      CMA promotes osteoblast differentiation and calcium deposition in hBMSCs, whereas
      CMA treatment suppresses adipogenesis of hBMSCs. CMA activates and potentiates
      the phosphorylation of extracellular signal-regulated kinases (ERK1/2) in an
      osteogenic differentiation conditions. In addition, CMA-stimulated osteoblast
      differentiation is suppressed by inhibiting the ERK pathway, suggesting that CMA
      promotes the osteogenic differentiation program of hBMSCs through the ERK
      activation. Taken together, these results suggest a novel function of CMA as an
      osteogenic activator and intracellular signaling pathway mediated by CMA in
      osteoblast differentiation.

PMID- 24440167
TI  - A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an
      LTB4 receptor antagonist) for the treatment of lung disease in children and
      adults with cystic fibrosis.
AB  - BACKGROUND: Airway inflammation, mediated in part by LTB4, contributes to lung
      destruction in patients with cystic fibrosis (CF). LTB(4)-receptor inhibition may
      reduce airway inflammation. We report the results of a randomized, double-blind,
      placebo-controlled study of the efficacy and safety of the leukotriene B(4)
      (LTB(4))-receptor antagonist BIIL 284 BS in CF patients. METHODS: CF patients
      aged >=6 years with mild to moderate lung disease were randomized to oral BIIL
      284 BS or placebo once daily for 24 weeks. Co-primary endpoints were change in
      FEV(1) and incidence of pulmonary exacerbation. RESULTS: After 420 (155 children,
      265 adults) of the planned 600 patients were randomized, the trial was terminated
      after a planned interim analysis revealed a significant increase in pulmonary
      related serious adverse events (SAEs) in adults receiving BIIL 284 BS. Final
      analysis revealed SAEs in 36.1% of adults receiving BIIL 284 BS vs. 21.2%
      receiving placebo (p = 0.007), and in 29.6% of children receiving BIIL 284 BS vs.
      22.9% receiving placebo (p = 0.348). In adults, the incidence of protocol-defined
      pulmonary exacerbation was greater in those receiving BIIL 284 BS than in those
      receiving placebo (33.1% vs. 18.2% respectively; p = 0.005). In children, the
      incidence of protocol-defined pulmonary exacerbation was 19.8% in the BIIL 284 BS
      arm, and 25.7% in the placebo arm (p = 0.38). CONCLUSIONS: While the cause of
      increased SAEs and exacerbations due to BIIL 284 BS is unknown, the outcome of
      this trial provides a cautionary tale for the administration of potent anti
      inflammatory compounds to individuals with chronic infections, as the potential
      to significantly suppress the inflammatory response may increase the risk of
      infection-related adverse events.

PMID- 24440172
TI  - Impaired working memory by repeated neonatal MK-801 treatment is ameliorated by
      galantamine in adult rats.
AB  - Early life blockade of the NMDA receptor by using MK-801, a non-competitive NMDA
      receptor antagonist, induces behavioral changes that mimic several features of
      schizophrenia. In the current study, we first examined the effects of neonatal MK
      801 treatment in male Sprague-Dawley rats on locomotor activity, prepulse
      inhibition and spatial working memory in adolescence (postnatal day 35, PND35)
      and adulthood (PND63). Next, we investigated the effects of an
      acetylcholinesterase inhibitor, galantamine, on working memory deficits induced
      by MK-801 treatment. Rats were treated with either saline or MK-801 (0.25mg/kg
      twice daily) at PND 5-14, and the long-term behavioral effects were investigated.
      MK-801 treated rats showed moderate working memory impairments in adolescence but
      a pronounced deficit in adulthood. However, locomotion and prepulse inhibition at
      two life stages were not affected by this treatment. Systemic administration of
      galantamine (1mg/kg) 30 min before each training session significantly improved
      neonatal MK-801-induced working memory deficits in adulthood. In conclusion,
      these results suggest that the neonatal MK-801 treatment-induced selective
      working memory deficit is related to a change in brain cholinergic systems.

PMID- 24440173
TI  - Evolution of sex determination and sexually dimorphic larval sizes in parasitic
      barnacles.
AB  - The parasitic (rhizocephalan) barnacles include species of which larval sex is
      determined by the mother (genetic sex determination, GSD), male larvae are larger
      than female larvae, and a female accepts only two dwarf males who sire all the
      eggs laid by her. In contrast, other species of parasitic barnacles exhibit
      monomorphic larvae that choose to become male or female depending on the
      condition of the host they settle (environmental sex determination, or ESD), and
      a female accepts numerous dwarf males. Here, we ask why these set of traits are
      observed together, by examining the evolution of sex determination and the larval
      size. ESD has an advantage over GSD because each larva has a higher chance of
      encountering a suitable host. On the other hand, GSD has two advantages over ESD:
      the larval size can be chosen differently between sexes, and their larvae can
      avoid spending time for sex determination on the host. We conclude that, in
      species whose female accepts only two males, the male larvae engage in intense
      contest competition for reproductive opportunities, and male's success-size
      relation is very different from female's. Then, larvae with predetermined sex
      (GSD) with sexually dimorphic larvae is more advantageous than ESD. In contrast,
      in species whose females accept many dwarf males, the competition among males is
      less intense, and producing larvae with undetermined sex should evolve. We also
      discuss the condition for females to evolve receptacles to limit the number of
      males she accepts. 

PMID- 24440174
TI  - Impact of mating behaviour on the success of malaria control through a single
      inundative release of transgenic mosquitoes.
AB  - Transgenic mosquitoes are a potential tool for the control or eradication of
      insect-vectored diseases. For malaria, one possible strategy relies on the
      introduction of malaria-refractory transgenes into wild Anopheles mosquito
      populations that would limit their capacity to transmit the disease. The success
      of such an approach obviously depends on a variety of factors. By developing a
      model that integrates both population genetics and epidemiology, we explore how
      mosquito mating preferences and the cost and efficacy of refractoriness affects
      the long-term prevalence of malaria in humans subsequent to a single generation
      inundative release of male transgenic mosquitoes. As may be intuitively expected,
      mating discrimination by wild-type individuals against transgenic ones generally
      reduces the probability that transgenes become stably established at a high
      frequency in mosquito populations. We also show that in circumstances where
      transgenic individuals exhibit some degree of discrimination against wild-type
      individuals, this can favour the spread of refractory alleles and lead to a
      significant reduction in malaria prevalence in the human population (if the
      efficacy of a dominant refractory mechanism exceeds at least 75%). The existence
      of such a non-intuitive outcome highlights the practical value of increasing the
      understanding of Anopheles mating preferences in the wild as a means to harness
      them in the implementation of population replacement approaches. Potential
      strategies by which previously described mating preferences of Anopheles gambiae
      populations could be exploited to manipulate the mate choice of transgenic
      release stocks are discussed. 

PMID- 24440175
TI  - A co-expression modules based gene selection for cancer recognition.
AB  - Gene expression profiles are used to recognize patient samples for cancer
      diagnosis and therapy. Gene selection is crucial to high recognition performance.
      In usual gene selection methods the genes are considered as independent
      individuals and the correlation among genes is not used efficiently. In this
      description, a co-expression modules based gene selection method for cancer
      recognition is proposed. First, in the cancer dataset a weighted correlation
      network is constructed according to the correlation between each pair of genes,
      different modules from this network are identified and the significant modules
      are selected for following exploration. Second, based on these informative
      modules information gain is applied to selecting the feature genes for cancer
      recognition. Then using LOOCV, the experiments with different classification
      algorithms are conducted and the results show that the proposed method makes
      better classification accuracy than traditional gene selection methods. At last,
      via gene ontology enrichment analysis the biological significance of the co
      expressed genes in specific modules was verified. 

PMID- 24440176
TI  - Long-term highly suppressed HIV-infected children and adolescents with negative
      rapid HIV tests due to significant antibody loss.
AB  - BACKGROUND: Rapid HIV test devices are widely used throughout the world and are
      important as diagnostic tools with relatively high sensitivity and specificity.
      Loss of HIV specific antibodies in late-stage AIDS patients has previously been
      reported in patients with advanced disease (i.e., AIDS). OBJECTIVE: To study rate
      of antibody loss that may lead to false negative HIV-antibodies results in
      children and adolescents who received long term antiretroviral (ARV) treatment
      with persistently undetectable viral loads. STUDY DESIGN: Five FDA approved rapid
      HIV test kits including Trinity Uni-Gold Recombigen HIV-1, OraQuick Advance HIV
      1/2, Reveal G3 HIV-1, Clearview STAT-PAK HIV-1/2, and Clearview COMPLETE HIV-1/2
      were used to test 98 stored samples from 27 patients. Samples were tested at
      baseline and at least twice in 6-14 years post initiation of ARV treatment and
      full viral load suppression. RESULTS: Of the 403 tests, 43 (10.7%) were found to
      be false-negative using rapid HIV kits. Loss of positivity was correlated with
      decrease of HIV antibody titer. CONCLUSIONS: There is a slow but persistent loss
      of HIV specific antibodies in highly suppressed HIV infected children and
      adolescents that may lead to false-negative results in rapid HIV antibody tests.
      The temporal loss of signal is dependent on the baseline level of antibodies and
      the type of HIV rapid test kit used.

PMID- 24440177
TI  - Analytical characterization of an assay designed to detect and identify diverse
      agents of disseminated viral infection.
AB  - BACKGROUND: Diverse viruses often reactivate in or infect cancer patients,
      patients with immunocompromising infections or genetic conditions, and transplant
      recipients undergoing immunosuppressive therapy. These infections can
      disseminate, leading to death, transplant rejection, and other severe outcomes.
      OBJECTIVES: To develop and characterize an assay capable of inclusive and
      accurate identification of diverse potentially disseminating viruses directly
      from plasma specimens. STUDY DESIGN: We developed a PCR/electrospray ionization
      mass spectrometry (PCR/ESI-MS) assay designed to simultaneously detect and
      identify adenovirus, enterovirus, polyomaviruses JC and BK, parvovirus B19, HSV
      1, HSV-2, VZV, EBV, CMV, and herpesviruses 6-8 in plasma specimens. The assay
      performance was characterized analytically, and the results from clinical plasma
      samples were compared to the results obtained from single-analyte real time PCR
      tests currently used in clinical practice. RESULTS: The assay demonstrated
      sensitivity and specificity to diverse strains of the targeted viral families and
      robustness to interfering substances and potentially cross reacting organisms.
      The assay yielded 94% sensitivity when testing clinical plasma samples previously
      identified as positive using standard-of-care real-time PCR tests for a single
      target virus (available samples included positive samples for 11 viruses targeted
      by the assay). CONCLUSIONS: The assay functioned as designed, providing
      simultaneous broad-spectrum detection and identification of diverse agents of
      disseminated viral infection. Among 156 clinical samples tested, 37 detections
      were made in addition to the detections matching the initial clinical positive
      results.

PMID- 24440178
TI  - Interactions in multispecies biofilms: do they actually matter?
AB  - The recent focus on complex bacterial communities has led to the recognition of
      interactions across species boundaries. This is particularly pronounced in
      multispecies biofilms, where synergistic interactions impact the bacterial
      distribution and overall biomass produced. Importantly, in a number of settings,
      the interactions in a multispecies biofilm affect its overall function,
      physiology, or surroundings, by resulting in enhanced resistance, virulence, or
      degradation of pollutants, which is of significant importance to human health and
      activities. The underlying mechanisms causing these synergistic effects are to
      some extent characterized at the molecular and evolutionary levels, and further
      exploration is now possible due to the enhanced resolution and higher throughput
      of available techniques. 

PMID- 24440179
TI  - Normalized gradient fields for nonlinear motion correction of DCE-MRI time
      series.
AB  - Dynamic MR image recordings (DCE-MRI) of moving organs using bolus injections
      create two different types of dynamics in the images: (i) spatial motion
      artifacts due to patient movements, breathing and physiological pulsations that
      we want to counteract and (ii) signal intensity changes during contrast agent
      wash-in and wash-out that we want to preserve. Proper image registration is
      needed to counteract the motion artifacts and for a reliable assessment of
      physiological parameters. In this work we present a partial differential equation
      based method for deformable multimodal image registration using normalized
      gradients and the Fourier transform to solve the Euler-Lagrange equations in a
      multilevel hierarchy. This approach is particularly well suited to handle the
      motion challenges in DCE-MRI time series, being validated on ten DCE-MRI datasets
      from the moving kidney. We found that both normalized gradients and mutual
      information work as high-performing cost functionals for motion correction of
      this type of data. Furthermore, we demonstrated that normalized gradients have
      improved performance compared to mutual information as assessed by several
      performance measures. We conclude that normalized gradients can be a viable
      alternative to mutual information regarding registration accuracy, and with
      promising clinical applications to DCE-MRI recordings from moving organs. 

PMID- 24440180
TI  - Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver
      disease: a multicenter experience.
AB  - BACKGROUND: Diabetes is associated with increased morbidity and mortality in
      patients with cystic fibrosis (CF). While liver transplantation is well
      established for CF-related liver disease (CFLD), the role of simultaneous liver
      pancreas transplantation is less understood. METHODS: We polled 81 pediatric
      transplantation centers to identify and characterize subjects who had undergone
      simultaneous liver-pancreas transplantation and obtain opinions about this
      procedure in CFLD. RESULTS: Fifty (61.7%) polled transplant centers responded and
      94% reported that they would consider simultaneous liver-pancreas transplantation
      for CFLD and diabetes. A total of 8 patients with simultaneous liver-pancreas
      transplantation were identified with median follow up of 38 months. All patients
      had pre-existing diabetes. Exocrine and endocrine pancreatic function was
      initially restored in all patients with later functional loss in one patient.
      Body mass index Z-score increased between one year pre-transplantation and one
      year post-transplantation (P=0.029). CONCLUSIONS: Patients with CFLD undergoing
      initial assessment for liver transplantation may benefit from consideration of
      simultaneous liver-pancreas transplantation.

PMID- 24440181
TI  - The relative frequency of CFTR mutation classes in European patients with cystic
      fibrosis.
AB  - More than 1900 different mutations in the CFTR gene have been reported. These are
      grouped into classes according to their effect on the synthesis and/or function
      of the CFTR protein. CFTR repair therapies that are mutation or mutation class
      specific are under development. To progress efficiently in the clinical phase of
      drug development, knowledge of the relative frequency of CFTR mutation classes in
      different populations is useful. Therefore, we describe the mutation class
      spectrum in 25,394 subjects with CF from 23 European countries. In 18/23
      countries, 80% or more of the patients had at least one class II mutation,
      explained by F508del being by far the most frequent mutation. Overall 16.4% of
      European patients had at least one class I mutation but this varied from 3
      countries with more than 30% to 4 countries with less than 10% of subjects.
      Overall only respectively 3.9, 3.3 and 3.0% of European subjects had at least one
      mutation of classes III, IV and V with again great variability: 14% of Irish
      patients had at least one class III mutation, 7% of Portuguese patients had at
      least one class IV mutation, and in 6 countries more than 5% of patients had at
      least one class V mutation. 

PMID- 24440182
TI  - Preemptive coil occlusion of major aberrant renal artery to allow endovascular
      repair of abdominal aortic aneurysm with crossed fused renal ectopia.
AB  - BACKGROUND: Crossed fused renal ectopia and other similar renal anomalies are
      nearly always associated with major renal arterial, venous, and collecting system
      anomalies. These complicate both open repair and endovascular repair (EVAR) of
      abdominal aortic aneurysms (AAA). We present a case of successful EVAR of an AAA
      with crossed fused renal ectopia. PATIENT DESCRIPTION: A 76-year-old man was
      followed with an AAA and was also noted to have crossed fused renal ectopia. The
      aneurysm increased in diameter to 5.5 cm, and repair was recommended. Anatomy
      appeared challenging for open repair but also for EVAR because of a highly
      angulated neck and the major renal artery to the ectopic segment originating from
      the upper part of the aneurysm. However, EVAR appeared feasible if this renal
      artery could be sacrificed. Coil embolization of this renal artery was performed
      before EVAR. The patient's renal function was stable, and he suffered only a few
      days of abdominal pain. EVAR was performed 25 days later and required adjunctive
      procedures to eliminate a type 1 endoleak as had been feared because of the
      highly angulated neck. The patient suffered no decline in renal function and
      remained well 6 months later with no evidence for endoleak or other complication.
      COMMENT: Renal anomalies present major challenges in aortic aneurysm repair.
      Preemptive sacrifice of a portion of the renal mass may allow successful repair
      without apparent deleterious effects.

PMID- 24440183
TI  - Catheter-directed thrombolysis and stenting in the treatment of iliac vein
      compression syndrome with acute iliofemoral deep vein thrombosis: outcome and
      follow-up.
AB  - BACKGROUND: The purpose of this study was to evaluate the safety and
      effectiveness of catheter-directed thrombolysis (CDT) and stenting in the
      treatment of iliac vein compression syndrome (IVCS) with acute iliofemoral deep
      vein thrombosis (DVT). METHODS: A retrospective analysis was conducted in 61
      patients (36 women, 25 men, age range 32-90 years, mean 64 years) who had IVCS
      with acute iliofemoral thrmobosis (<=10 days) and were treated by CDT and
      stenting between June 2006 and August 2011. All patients presented with IVCS with
      a median duration of 4.1 days and were treated with CDT (urokinase: initial dose
      of 125,000-250,000 U followed by 20,000-60,000 U/hr) followed by stent placement.
      Filters were implanted in those patients with existing pulmonary embolism (PE),
      inferior caval vein thrombosis, or in accordance with the patients' request. The
      patency, the pressure gradient crossing the stenosis of the iliac vein, both
      thigh and calf limb circumferences, and complications were assessed before and
      after CDT and stenting. A Duplex ultrasound was used to perform follow-up
      examinations at 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
      after the operation. RESULTS: Three patients had PE before CDT as assessed by the
      computed tomography angiography. A total of 28 patients had a filter implanted
      (25 patients had a Cordis permanent filter and 3 patients had a Braun temporary
      filter). A total of 68 stents were implanted in 61 patients. Overall, the 1
      month, 6-month, 1-year, 2-year, 3-year, and 5-year primary patency rates were
      96.7%, 95.1%, 91.8%, 90.2%, 88.5%, and 85.2%, respectively. The pressure gradient
      crossing the stenosis of the iliac vein decreased significantly after CDT and
      stenting (7.22 +/- 4.64 vs. 1.82 +/- 2.78 cm H2O, P < 0.001). The reductions of
      thigh and calf circumferences were 66.7% (6.19 +/- 2.67 vs. 1.98 +/- 1.43 cm) and
      61.6% (4.36 +/- 2.10 vs. 1.46 +/- 1.10 cm), respectively. Reocclusion occurred in
      7 patients within 1-27 months. Four patients (7%) experienced minor bleeding and
      were treated successfully with sandbag compression. One patient felt light pain
      on the left waist after 3 months of stenting. No large hematoma, stent migration,
      or acute thrombosis complications occurred during the procedure. Two patients
      died from nonvascular causes during a follow-up of 2-62 months (mean, 31.0
      months). Four patients were found with limb swelling and three patients felt
      heaviness. The incidence rate of postthrombotic syndrome was 11.5% (7/61).
      CONCLUSIONS: Treatment with CDT for IVCS with acute DVT achieves good patency and
      vein function after 5 years of follow-up in this study. However, further evidence
      is required to establish longer term benefits.

PMID- 24440184
TI  - Management of recurrent iliac artery stenosis in individuals aged 55 or less.
AB  - Aortoiliac disease is the most common location for symptomatic peripheral
      arterial disease in young patients. Angioplasty with stenting has become the
      initial treatment of choice for most patients. However, the treatment of
      recurrence is poorly studied, particularly in those who are considered candidates
      for surgical bypass. We reviewed our experience in 64 patients (91 limbs), mean
      age 48 years, who were treated with angioplasty (3%), repeat stenting (91%), or
      bypass (5%) for recurrent symptoms. These patients had TASC II A/B lesions
      predominantly of the common iliac arteries (78%). Time to retreatment was 13.6
      months after the initial procedure mainly for claudication (mean ankle-brachial
      index 0.64). Primary, primary-assisted, and secondary patency rates for
      angioplasty were 85 +/- 9%, 93 +/- 7%, 100% after angioplasty; 76 +/- 6%, 94 +/-
      3%, 96 +/- 3% after stenting; and 86 +/- 9% after bypass surgery at 12 months.
      Amputation-free survival rates were not statistically different out to 4 years.
      In conclusion, endovascular reintervention and bypass surgery demonstrate similar
      outcomes in patients with recurrent symptoms after failed angioplasty with
      stenting.

PMID- 24440185
TI  - The role of procalcitonin in postimplantation syndrome after EVAR: a pilot study.
AB  - BACKGROUND: After endovascular aortic repair (EVAR) for treatment of aortoiliac
      aneurysms, patients commonly develop an inflammatory reaction: Postimplantation
      syndrome (PIS). Clinically, it may be hard to separate PIS from an infectious
      complication. Procalcitonin (PCT) is a diagnostic marker for severe bacterial
      infections and sepsis. We hypothesize that low-PCT levels facilitate the PIS
      diagnosis after EVAR. METHODS: Sixty-nine elective EVAR patients were included.
      Tympanic temperature, C-reactive protein (CRP), white blood cell count (WBC), and
      PCT were measured on days -1 and +1, +3 and +5. Complications, in-hospital stay,
      and infections were recorded. PIS was defined by a body temperature of >=38
      degrees C and WBC >=12,000/MUL combined with no other detected complication or
      surgical event explaining the inflammatory response. Three cohort subgroups were
      compared: the noncomplication group, those with PIS, and the patients with
      complications or additional open surgical events. RESULTS: All patients developed
      various extents of postoperative inflammatory responses including a rise in WBC,
      CRP, and/or temperature. PIS was diagnosed in 12 patients. Forty patients had no
      complication and seventeen suffered complications or had an additional open
      surgical event. All PIS patients showed low-PCT levels. On day +3, in the PIS
      group, median PCT was 0.22 ng/mL (95% confidence interval [CI]: 0.15-0.28), WBC
      13.2 * 10(9)/L (11.4-15.6), and CRP 196 mg/L (149-243). High PCT was observed in
      6 patients, out of which 4 had complications or additional open surgical
      procedures. CONCLUSIONS: In patients with PIS after EVAR, there was a strong
      inflammatory reaction. In the PIS condition, PCT remains low. This pilot study
      shows that PCT may be useful for the PIS diagnosis.

PMID- 24440186
TI  - Carotid duplex ultrasound changes associated with left ventricular assist
      devices.
AB  - BACKGROUND: Carotid duplex ultrasound (CDUS) is often used as a screening test in
      cardiac patients. Significant cardiac dysfunction may affect the accuracy of CDUS
      because of alterations in the cardiac cycle. Left ventricular assist devices
      (LVADs) are frequently implanted as a bridge to cardiac transplant. A review of
      CDUS in patients with LVADs was performed to assess their influence on arterial
      waveforms and velocities. METHODS: Patients with LVADs undergoing carotid duplex
      in our Intersocietal Commission for the Accreditation of Vascular Laboratories
      (ICAVL)-accredited vascular laboratory were identified. The carotid waveforms
      were analyzed qualitatively and quantitatively. Common carotid artery (CCA) and
      internal carotid artery (ICA) peak-systolic and end-diastolic velocities (PSV and
      EDV) were recorded as ICA/CCA velocity ratios. In patients with prior CDUS, the
      changes between these values were analyzed before and after LVAD placement.
      RESULTS: Of the 14 patients with LVADs treated in our institution over the past 2
      years, 4 had CDUS (8 ICAs). Mean age was 57 years, and 3 of the 4 patients were
      men. All patients were free of cerebrovascular symptoms. Qualitatively, there was
      significant blunting of the CCA and ICA waveforms noted in all 8 ICAs. The degree
      of stenosis was reported as <=15% in 7 ICAs and 15-45% in 1 ICA. The mean ICA PSV
      was 61.8 cm/sec. Two patients (4 ICAs) had CDUS before and after LVAD placement.
      Comparing pre- and post-LVAD values, the mean ICA PSV decreased by 42% (54
      cm/sec; P = 0.04) and EDV increased by 51% (17 cm/sec; P = 0.3). The PSV and EDV
      ratios were unchanged. Overall assessment of category of stenosis was unchanged
      in 2 ICAs (<=15%), one decreased from moderate to mild (45-70% to 15-45%), and
      one ICA changed from 45-70% to <=15% based on the decreased ICA PSV. CONCLUSIONS:
      The presence of an LVAD has a significant influence on CDUS findings. There is a
      qualitative change in the ICA with blunting of the waveform, and a quantitative
      change with a decreased PSV and an increased EDV. Compared with pre-LVAD
      placement, there is a significant decrease in PSV which may affect the accuracy
      of CDUS using velocity-based criteria. Further study into the accuracy of CDUS in
      patients with LVADs is necessary.

PMID- 24440187
TI  - Sympathetic hyperactivity and aortic sympathetic nerve sprouting in patients with
      thoracic aortic dissection.
AB  - BACKGROUND: To determine the yet unknown relation between thoracic aortic
      dissection (TAD) and sympathetic nervous system activity. METHODS: Variables such
      as electrocardiography, blood pressure, respiratory activity, postganglionic
      muscle sympathetic nerve activity (MSNA), plasma norepinephrine, tyrosine
      hydroxylase-positive nerve fiber density, and growth-associated protein 43
      positive nerve fiber density were detected and statistically analyzed. RESULTS:
      TAD Patients showed a significant lower R-R interval variance and higher blood
      pressure, heart rate, respiratory rate, MSNA, plasma norepinephrine (reflecting
      elevated sympathetic nervous system [SNS] activity), higher tyrosine hydroxylase,
      growth-associated protein 43-positive nerve fiber density (reflecting sympathetic
      sprouting and innervation) than those of the control group. CONCLUSIONS: In TAD
      patients, both overall and regional aortic SNS activities are elevated.

PMID- 24440188
TI  - Characterization of the kallikrein-kinin system, metalloproteinases, and their
      tissue inhibitors in the in-stent restenosis after peripheral percutaneous
      angioplasty.
AB  - BACKGROUND: The kallikrein-kinin system (KKS) has several direct and indirect
      effects on cells and cellular mediators involved in the inflammatory process.
      Studies about inflammation on percutaneous transluminal angioplasty with stent
      (PTA/stent) to treat peripheral arterial disease (PAD) in humans are scarce. The
      matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing
      endopeptidases expressed in various cells and tissues such as fibroblasts,
      inflammatory cells, and, smooth muscle cells. Changes in the extracellular matrix
      (ECM) take place in the pathogenesis of many cardiovascular pathologies. MMPs and
      their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are crucial in
      ECM remodeling in both physiologic and pathologic conditions. The aim of this
      study was to evaluate the role of the KKS and the MMP metabolism, which are
      important mediators that may contribute to tissue repair, in the process of
      arterial restenosis due to intimal hyperplasia in the femoropopliteal segment
      with the aim of developing new interventions. METHODS: Thirty-nine consecutive
      patients were selected (regardless of ethnic group, age, or sex) for
      revascularization, who underwent PTA/stent of the femoropopliteal segment. Twenty
      five patients with the same clinical characteristics who were scheduled for
      diagnostic angiography but not subjected to PTA/nitinol stent were also selected.
      The concentrations in blood of total and kininogen fractions were evaluated using
      immunoenzymatic methods. Plasma kallikrein was evaluated by the colorimetric
      method. Tissue kallikrein was evaluated by the spectrophotometric method. The
      activity of kininase II was measured by fluorometric analysis. Quantification of
      MMPs was performed by zymography, which is an electrophoresis technique, and
      TIMPs were measured by enzyme-linked immunosorbent assay. RESULTS: Among the 31
      patients who completed the survey, there were 10 cases of angiographically
      defined restenosis of >50%, and 21 cases without restenosis. There was an
      increase in the concentrations of the substrates (high-molecular-weight
      kininogens and lower molecular weight kininogens) and enzymes (plasma and tissue
      kallikrein) in patients with restenosis, indicating activation of this
      inflammatory pathway in these patients. The activity of kininase II was not
      significantly different between the groups of patients studied. There were no
      statistical differences between restenosis and no restenosis patients for both
      MMPs and TIMPs dosage, but there is an upward trend of MMPs in time 6 months in
      patients with restenosis. CONCLUSIONS: With the aim of identifying factors
      contributing to restenosis after endovascular intervention, this study showed
      evidence of high activation of the KKS in the pathologic inflammatory process of
      PTA/stent restenosis. In the other hand, it could not show participation of
      metalloproteinase metabolism in PTA/stent restenosis.

PMID- 24440189
TI  - Endovascular management of visceral artery aneurysms with flow-diverting stents.

PMID- 24440190
TI  - A deceitful case of spinal cord malperfusion presented as an acute limb ischemia.
AB  - We present an interesting case of a patient with spinal cord ischemia presented
      with physical and angiographic findings of acute right leg ischemia 6 days after
      abdominal aortic aneurysm open repair. After unsuccessful transpopliteal
      thrombectomy, patient was treated with spinal cord drainage. Cause of this
      complication might be ischemic lumbal plexopathy. 

PMID- 24440191
TI  - Comment on endovascular stent placement for treatment of spontaneous isolated
      dissection of the superior mesenteric artery.

PMID- 24440192
TI  - The chimney technique with the Ovation Trivascular device: new kid on the block!

PMID- 24440193
TI  - Endoscopic-assisted robotic aortic thrombectomy and aortobiiliac bypass: a case
      report.
AB  - In this report, not only our experience with laparoscopy-assisted robotic aortic
      thrombectomy and aortobiiliac bypass procedure was presented but also current
      status of vascular interventions via endoscopically was discussed. 

PMID- 24440194
TI  - Endovenous laser ablation of great saphenous veins performed using tumescent cold
      saline solution without local anesthesia.
AB  - BACKGROUND: In recent years, laser systems with higher wavelengths, associated
      with new optical fibers, have shown excellent short-term results in treating
      saphenous veins and reducing the side effects and, in particular, the
      postoperative pain. However, if the patients are not anesthetized, they may feel
      pain even when using low energy with the high-wavelength laser; the only
      tumescent local anesthesia often does not guarantee a complete pain control
      during endovenous laser ablation (EVLA). Aim of this study was to demonstrate
      that the local anesthesia during EVLA of great saphenous veins (GSVs) is not
      essential for the perioperative comfort of the patient if a mild sedation is
      made. METHODS: Forty-nine incompetent GSVs were treated by EVLA with a cold
      saline tumescent solution (CSTS) without local anesthetic drugs. EVLA was
      performed with a 1540-nm diode laser and a 600-MUc ball-tipped fiber.
      Intraoperative ultrasonography was then used to guide delivery of CSTS (cold
      saline solution 0.9% at 5 degrees C) using a motor pump under intravenous
      sedation. The gravity of chronic venous disease was determined according to the
      clinical-etiology-anatomy-pathophysiology classification. Patients rated surgery
      global pain according to 4 types: "extremely," "rather," "slightly," and "not at
      all" painful. RESULTS: Twenty-five cases (51%) were classified as C3, 20 (41%) as
      C2, 6 (13%) as C4, and 1 (2%) as C6. Midazolam 2.5 mg + a mean of 0.16 mg of
      fentanil (minimum: 0.10; maximum: 0.20; standard deviation [SD]: 0.4) + a mean of
      178.21 mg of propofol (minimum: 100; maximum: 300; SD: 47.1) were administrated
      as intravenous sedation. The total average linear endovenous energy density was
      57.7 J/cm. Approximately 250 mL (minimum: 100; maximum: 780) of CSTS was
      administered. No Patient has had pain during the procedure. All patients were
      discharged 2.5 hrs after surgery. CONCLUSIONS: EVLA under sedation using CSTS
      without diluted anesthetic drugs is a suitable technique in an outpatients
      clinic, especially useful if the ablation of the saphenous vein is combined with
      an extended phlebectomy or if a bilateral treatment is performed, to eliminate
      the risks of overdose with local anesthesia and with the aim of improving the
      comfort of the patient.

PMID- 24440195
TI  - Basic data related to thrombolytic therapy for acute venous thrombosis.
AB  - BACKGROUND: Treatment guidelines for thrombolysis in iliofemoral deep venous
      thrombosis (DVT) are based on a limited number of observational and prospective
      studies. The acute venous thrombosis: thrombus removal with adjunctive catheter
      directed thrombolysis (ATTRACT) trial will be the first large, multicenter
      randomized control trial to evaluate the relative advantages of several current
      treatment strategies. The objective of this study was to summarize the existing
      data that inform the use of catheter-directed thrombolysis (CDT) or
      pharmacomechanical thrombectomy in the management of acute iliofemoral DVT.
      METHODS: A search of the current literature was done using PubMed, Ovid, and
      Cochrane databases for all available articles published up to December 2013.
      RESULTS: Of those studies, which included at least 25 patients, 19 case series
      were identified from 1996 to 2012. Treatment groups included anticoagulation,
      surgical thrombectomy, pharmacomechanical thrombectomy, and CDT. Cases observed
      in each ranged from 26 to 101. Three studies were identified which derived data
      from national multicenter registries. Only 2 randomized control trials were
      identified from 2002 to 2012. Both support the use of CDT over anticoagulation
      alone for treatment of iliofemoral DVT. CONCLUSIONS: Present treatment guidelines
      for acute iliofemoral DVT have been in flux and are derived from a relatively
      small amount of clinical data. They are summarized here in anticipation of
      results from the ongoing ATTRACT trial.

PMID- 24440196
TI  - Item-based analysis of delayed reward discounting decision making.
AB  - Delayed reward discounting (DRD) is a behavioral economic index of time
      preference, referring to how much an individual devalues a reward based on its
      delay in time, and has been linked to a wide array of health behaviors. It is
      commonly assessed using a task that asks participants to make dichotomous choices
      between two monetary rewards, one available immediately and the other after a
      delay. This study sought to shorten an extended iterative DRD assessment to
      increase its versatility and efficiency. Data were drawn from two young adult
      samples, an exploratory sample (N=130) and a confirmatory sample (N=247). In the
      exploratory sample, eight items were identified as predicting the majority of the
      variance in the full task area under the curve (AUC) (R(2)=.821; p<.001). In the
      confirmatory sample, the same eight items similarly predicted the majority of
      variance in the full task AUC (R(2)=.844, p<.001). These results provide initial
      support for the validity of a brief 8-item assessment of DRD. Priorities for
      further validation and potential applications are discussed. 

PMID- 24440197
TI  - Paclitaxel-induced hyperalgesia modulates negative affective component of pain
      and NR1 receptor expression in the frontal cortex in rats.
AB  - Paclitaxel, one of the chemotherapeutic agents clinically used to treat several
      types of cancer, produces side effects such as peripheral neuropathy, sensory
      abnormalities, and hyperalgesia. Since hyperalgesia remains after cessation of
      paclitaxel therapy and becomes chronic, we hypothesize that alteration in memory
      and the cognitive process of pain underlies hyperalgesia. To test this
      hypothesis, we examined whether drug-induced hyperalgesia alters the affective
      component of pain and the NMDA-NR1 and mGluR1 receptors as a mediator for signal
      transmission and memory of pain. Mechanical sensitivity was measured by von Frey
      filament test after intraperitoneal injection of paclitaxel in rats. Paclitaxel
      induced hyperalgesia was confirmed over almost the entire 14-day period of
      observation after the treatment. The effect of paclitaxel-induced hyperalgesia on
      the affective component of pain was assessed using pain-induced place aversion.
      The formalin-induced conditioned place aversion was completely abolished in the
      paclitaxel-treated rats. Immunoblot analysis of NR1 and mGluR1 protein levels in
      various brain regions was performed after paclitaxel treatment. Treatment reduced
      only the NR1 expression within the frontal cortex. These results suggest that the
      hypofunction of memory processes with the reduced NMDA receptors in the frontal
      cortex might be involved in the expression of abnormal emotional behaviors
      accompanied by hyperalgesia. 

PMID- 24440198
TI  - Dexamethasone induced changes of neural activity in the auditory cortex of rats.
AB  - Previous studies have suggested that elevation of glucocorticoid level can alter
      auditory processing and may have relevance for auditory hallucinations. However,
      the neural mechanism underlying the glucocorticoid induced sensory change remains
      unclear. To examine the effects of glucocorticoid on the neuronal spike
      activities of sensory cortex, we topically applied dexamethasone (DEX), a
      glucocorticoid receptor agonist, to the auditory cortical surface of rats while
      recording single-unit extracellular spike activities in response to sound
      stimuli. Our major findings are: (1) a topical administration of DEX increased
      the cortical neural responses to pure-tone stimuli from 10 to 60 min after
      administration, while the peak response enhancement occurred at 20-30 min; (2)
      DEX not only markedly increased the magnitude of tone-evoked responses, but also
      extended the response duration and the frequency range of the neural responses;
      (3) the enhancement of neural responses was more salient at the higher frequency
      band; (4) the ratio of spontaneous firing rate between post- and pre
      administration was negatively correlated with the unit's spontaneous firing rate
      before treatment. Our data confirm that DEX can modulate the neural activity at
      the cortical level and provide more information for understanding the mechanism
      of glucocorticoid-induced alterations in auditory processing.

PMID- 24440199
TI  - Lack of schmallenberg virus in ruminant brain tissues archived from 1961 to 2010
      in Germany.
AB  - Schmallenberg virus (SBV) is an orthobunyavirus of the family Bunyaviridae that
      is associated with stillbirth and malformations in ruminants. The infection has
      been identified in many European countries since August 2011. The present study
      investigated retrospectively the occurrence of SBV infection in ruminants using
      immunohistochemistry and in-situ hybridization in brain tissues archived between
      1961 and 2010 (112 cattle, 57 sheep, 16 goats and 27 wild ruminants). Eighty-five
      animals with inflammatory brain lesions and 47 animals with malformations were
      included. Due to the lack of SBV protein and RNA detection, SBV appears to have
      been introduced recently into Northern parts of Europe from tropical or
      subtropical regions. 

PMID- 24440200
TI  - The immune response after stimulation with wall components of gram-positive
      bacteria and fungi.
AB  - Although several components of the microbial wall of gram-positive bacteria and
      fungi possess immunostimulatory properties, their pathogenetic role remains
      incompletely evaluated. The purpose of this study was to assess the basic immune
      status of patients susceptible to infections and their capability for cytokine
      production after stimulation with wall components of gram-positive bacteria and
      fungi. We measured serum cytokine levels as well as cytokine production after ex
      vivo lipoteichoic acid (LTA) and mannan stimulation of whole blood. The blood was
      taken from 10 healthy volunteers, 10 patients with end-stage renal disease
      (ESRD), 10 patients with diabetes mellitus (DM), and 10 patients on their 2nd day
      of stay in the Intensive Care Unit (ICU), who suffered from non septic systemic
      inflammatory response syndrome (SIRS) and had an APACHE II score >=25. We used 1
      MUg/ml LTA and 100 MUg/ml mannan for an incubation period of 8 h to stimulate 100
      MUl aliquots of whole blood. All patient groups had higher baseline values of TNF
      alpha, IL-6, IL-1beta, and IL-10 compared to the control group, but only for ICU
      patients the difference was statistically significant. The ratio IL-10/IL-6 was
      found 0.33, 0.22, and 0.96 in healthy persons, ESRD, and DM patients
      respectively, and 1.32 in ICU patients. In all examined groups, the levels of
      cytokines significantly increased after stimulation by LTA and mannan, although
      in severely ill patients this change was considerably smaller, possibly
      reflecting a state of monocytes' depression and relative hyporesponsiveness. No
      significant differences between the LTA and the mannan stimulation were observed.

PMID- 24440201
TI  - A rare case of large cell neuroendocrine carcinoma of the urinary bladder
      evaluated by 18F-FDG-PET/CT.

PMID- 24440203
TI  - Intact cost-effectiveness of screening for abdominal aortic aneurysms in Sweden.

PMID- 24440202
TI  - [Sentinel node biopsy in patients with multifocal and multicentric breast cancer:
      A 5-year follow-up].
AB  - OBJECTIVE: Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple
      breast cancer is a controversial issue. We have aimed to evaluate the efficacy of
      sentinel node (SN) detection in patients with multifocal or multicentric breast
      cancer as well as the safety of its clinical application after a long follow-up.
      MATERIAL AND METHODS: A prospective descriptive study was performed. Eighty-nine
      patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric)
      underwent SLNB. These patients were compared to those with unifocal neoplasia.
      Periareolar radiocolloid administration was performed in most of the patients.
      Evaluation was made at an average of 67.2 months of follow-up (32-126 months).
      RESULTS: Scintigraphic and surgical SN localization in patients with multiple
      breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra
      axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as
      a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN
      localization in multicentric cancer was slightly lower than in multifocal cancer
      (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs
      10%). Number of SN per patient was significantly higher in multicentric breast
      cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow
      up in multiple breast cancer patients group. CONCLUSIONS: SLNB performed by
      periareolar injection is a reliable and accurate staging procedure of patients
      with multiple breast cancer, including those with multicentric processes.

PMID- 24440204
TI  - Implementation of an electronic medical record does not change delivery of
      preventive care for HIV-positive patients.
AB  - PURPOSE: This study sought to determine the impact that an electronic medical
      record (EMR) had on the provision of preventive health measures - including
      obtaining serologies for viral hepatitis and administering vaccinations to non
      immune patients - to HIV patients at a hospital-based clinic. METHODS: Using a
      pre-post study design, we compared rates of preventive health delivery to HIV
      patients at an outpatient clinic during the use of a paper medical record (PMR)
      and after implementation of an EMR. Retrospective chart reviews were conducted at
      two time points: 12-16 months prior to and 24 months following EMR
      implementation. The records of 160 active patients were randomly selected for
      review during both time periods. RESULTS: There was no difference between the PMR
      and EMR samples with regard to the proportion of patients who had hepatitis A
      (83% in PMR group; 77% in EMR) and hepatitis C (94% in both groups) serologies
      measured or the proportion of eligible patients who were given hepatitis
      vaccinations. Slightly fewer patients had a serology for hepatitis B measured in
      the EMR sample. CONCLUSIONS: As EMR implementation expands, it is important to
      evaluate the effects that EMRs have on patient outcomes, including preventive
      health provision. Our study showed that after implementation of an EMR, the
      provision of most preventive care measures did not improve. This finding is in
      agreement with many published studies. Some studies have found positive effects
      from EMRs that may be attributable to specific aspects of EMRs. Further study of
      the effect of specific EMR attributes on health care outcomes is needed.

PMID- 24440205
TI  - Cross-neutralizing antibodies elicited by the Cervarix(r) human papillomavirus
      vaccine display a range of Alpha-9 inter-type specificities.
AB  - The highly efficacious human papillomavirus (HPV) vaccines contain virus-like
      particles (VLP) representing genotypes HPV16 and HPV18, which together account
      for approximately 70% of cervical cancer cases. Vaccine-type protection is
      thought to be mediated by high titer, type-specific neutralizing antibodies. The
      vaccines also confer a degree of cross-protection against some genetically
      related types from the Alpha-9 (HPV16-like: HPV31, HPV33, HPV35, HPV52, HPV58)
      and Alpha-7 (HPV18-like: HPV39, HPV45, HPV59, HPV68) species groups. Cross
      protection is coincident with the detection of low titer serum responses against
      non-vaccine types by vaccinees. Such antibodies may be the effectors of cross
      protection or their detection may be useful as a correlate or surrogate. This
      study evaluated whether cross-neutralization of HPV types from the Alpha-9
      species group is mediated by antibodies with a predominantly type-restricted
      specificity for HPV16 that nevertheless exhibit low affinity interactions with
      non-vaccine types, or by antibody specificities that demonstrate similar
      recognition of vaccine and non-vaccine types but are present at very low levels.
      Antibodies generated following Cervarix(r) vaccination of 13-14 year old girls
      were evaluated by pseudovirus neutralization, VLP ELISA and by enrichment of
      target antigen specificity using VLP-immobilized beads. Two-dimensional
      hierarchical clustering of serology data demonstrated that the antibody
      specificity profile generated by VLP ELISA was both quantitatively and
      qualitatively different from the neutralizing antibody specificity profile.
      Target-specific antibody enrichment demonstrated that cross-neutralization of non
      vaccine types was due to a minority of antibodies rather than by the weak
      interactions of a predominantly type-restricted HPV16 antibody specificity.
      Furthermore, cross-neutralization of non-vaccine types appeared to be mediated by
      multiple antibody specificities, recognizing single and multiple non-vaccine
      types, and whose specificities were not predictable from examination of the serum
      neutralizing antibody profile. These data contribute to our understanding of the
      antibody specificities elicited following HPV vaccination and have potential
      implications for vaccine-induced cross-protection.

PMID- 24440206
TI  - Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p
      transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria
      model.
AB  - We have previously reported the new formulation of polyethylimine (PEI) with
      gamma polyglutamic acid (gamma-PGA) nanoparticle (NP) to have provided Plasmodium
      yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced
      protective cellular and humoral immunity in the lethal mouse malaria model.
      PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate
      vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal
      sequence motif positive genes picked up using web-based bioinformatics tools;
      though the observed protection was not complete. Here, we observed augmented
      protective effect of PyTAM DNA vaccine by using PEI and gamma-PGA complex as
      delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant
      survival rate from lethal P. yoelii challenge infection compared with naked PyTAM
      plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and
      IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN
      gamma in the splenocytes and IL-4, IFN-gamma, IL-12 and TNF-alpha levels in the
      sera and in the supernatants from ex vivo splenocytes culture were all enhanced
      by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM
      protective immune response, and this enhancement was associated with increased DC
      activation and concomitant IL-12 production. 

PMID- 24440207
TI  - Increased measles-mumps-rubella (MMR) vaccine uptake in the context of a targeted
      immunisation campaign during a measles outbreak in a vaccine-reluctant community
      in England.
AB  - BACKGROUND: Following a measles outbreak in a vaccine-rejecting community between
      April and September 2011 in South-East England, local health agencies implemented
      a two-pronged measles-mumps-rubella (MMR) immunisation campaign from August to
      October offered at the local general practice where most cases were registered.
      The campaign included (a) accelerated vaccination of children earlier than
      scheduled (1st dose at 6-11 months, or 2nd dose at 18-39 months), (b) catch-up of
      those aged over 18 months who had had no MMR immunisations or were late for
      second MMR. We investigated the impact of the outbreak and campaign on the number
      of MMR doses given. MATERIALS AND METHODS: In January 2012, we collected
      information on MMR vaccination for children registered at the practice aged 6
      months-16 years on 1 August 2011, through the child health information system. We
      counted the number of MMR doses administered in 2011 and compared it to 2008-2010
      data. We estimated the proportion vaccinated among the children eligible for the
      accelerated and catch-up campaign. RESULTS: The local practice administered 257
      MMR doses in 2011, a 114% increase on the average for 2008-2010. Among children
      eligible for earlier MMR vaccination 5/26 (19%) received a first dose, and 34/57
      (60%) a second dose. Among children eligible for catch-up, 20/329 (6%) received
      their first MMR and 39/121 (32%) their second. Of 1538 children, the proportion
      completely unimmunised for MMR declined by 3 percentage-points after the
      outbreak. DISCUSSION: Uptake of MMR vaccination significantly increased during
      the outbreak following the immunisation campaign. Those amenable to MMR
      vaccination seem to have benefited from the campaign more than those with no
      previous vaccinations. Future evaluations should address what made a few parents
      change their mind and have their children vaccinated for the first time during
      the outbreak.

PMID- 24440208
TI  - Adverse events following immunization in Ontario's female school-based HPV
      program.
AB  - BACKGROUND: In September 2007, a school-based human papillomavirus (HPV)
      vaccination program targeting grade 8 girls (approximately 13 years old) and
      delivered by public health was implemented in Ontario, Canada. We assessed
      reports of adverse events following immunization (AEFI) from the school-based
      program as part of quadrivalent HPV (HPV4) vaccine safety surveillance and to
      contribute to a comprehensive HPV vaccine program evaluation. METHODS: AEFIs
      following HPV4 vaccine (Gardasil((r))) administered between September 1, 2007 and
      December 31, 2011 were extracted from the province's reportable disease system.
      Confirmed AEFI reports among females 12-15 years old (i.e. assumed to have
      received vaccine through the program) were included. Events were grouped
      according to provincial AEFI case definitions. Rates were calculated using doses
      distributed as the denominator. RESULTS: Between 2007 and 2011, 133 confirmed
      AEFIs were reported while 691,994 HPV4 vaccine doses were distributed in the
      school-based program. The overall reporting rate was 19.2 HPV4 AEFI per 100,000
      doses distributed. Annual reporting rates decreased from 30.0 to 18.3 per 100,000
      doses distributed. Frequently reported events included 'allergic reaction
      dermatologic/mucosa' (25%), 'rash' (22%), and 'local/injection site reaction'
      (20%); 26% of reports had a non-specific event of 'other severe/unusual events'
      selected. Ten serious AEFIs were reported (7.5% of reports) including 2
      anaphylaxis, 2 seizures, 1 thrombocytopenia and 1 death. Further review found
      that the reports of anaphylaxis did not meet the Brighton anaphylaxis definition
      and the death was attributed to a preexisting cardiac condition. CONCLUSIONS:
      Overall these findings are consistent with the safety profile of HPV4 vaccine
      from pre-licensure clinical trials and post-marketing surveillance reports and
      importantly, no new safety signals were identified, especially no reports of VTE
      in this younger female population. Continued assessment of HPV4 AEFI surveillance
      data may be important to detect and investigate safety signals.

PMID- 24440209
TI  - Assessment of viral interference using a chemical receptor blocker against avian
      influenza and establishment of protection levels in field outbreaks.
AB  - Avian influenza (AI) currently poses a serious problem for poultry farming
      worldwide. Its prevalence in Mexico, despite vaccination, has highlighted the
      need for new approaches to control AI and reduce the economic losses associated
      with its occurrence in susceptible birds. The different interactions between AI
      viruses (AIV) and cellular receptors have been described, along with the affinity
      of some viruses for certain types of species-specific receptors. This receptor
      ligand specificity, combined with an understanding of viral interference
      processes and their relevance in different viral models, permits the assessment
      of new strategies for controlling AIV. The present study was designed to
      investigate the feasibility of using viral interference as a novel approach for
      AIV control, taking advantage of the high receptor-ligand specificity between AIV
      and animal cells. The results from field outbreak tests and cell culture analysis
      along with measurements of specific antibodies against AIV demonstrate that the
      mortality associated with AI infection can be reduced by using a receptor blocker
      against AIV. This receptor blocker approach also has the potential to be used on
      an industrial scale for the efficient control of AIV. 

PMID- 24440210
TI  - Evaluation of immune responses to an oral typhoid vaccine, Ty21a, in children
      from 2 to 5 years of age in Bangladesh.
AB  - Young children are very susceptible to typhoid fever, emphasizing the need for
      vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is
      not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif)
      available in capsular formulation is only recommended for those over 5 years. We
      studied immune responses to a liquid formulation of Ty21a in children 2-5 years
      of age. Since children in developing countries are in general hypo responsive to
      oral vaccines, the study was designed to determine if anti-helminthic treatment
      prior to vaccination, improves responses. In a pilot study in 20 children aged 4
      5 years, the immune responses in plasma and in antibody in lymphocyte secretions
      (ALS) to the enteric coated capsule formulation of Ty21a was found to be
      comparable to a liquid formulation (P>0.05). Based on this, children (n=252) aged
      >= 2-<3 years and >=3-<5 years were randomized to receive a liquid formulation of
      Ty21a with and without previous anti-helminthic treatment. The vaccine was well
      tolerated with only a few mild adverse events recorded in <1% of the children. De
      worming did not improve immune responses and both age groups developed 32-71%
      IgA, IgG, and IgM responses in plasma and 63-86% IgA responses in ALS and stool
      specimens to a membrane preparation (MP) of Ty21a. An early MP specific
      proliferative T cell response was also seen. We recommend that safety and
      efficacy studies with a liquid formulation of the vaccine are carried out in
      children under five, including those less than two years of age to determine if
      Ty21a is protective in these age groups and applicable as a public health tool
      for controlling typhoid fever in high prevalence areas of typhoid fever including
      Bangladesh.

PMID- 24440211
TI  - Estimation of the economic and health impact of complications of type 2 diabetes
      mellitus in the autonomous community of Madrid (Spain).
AB  - OBJECTIVE: To estimate the economic and health impact of chronic complications
      (macrovascular and microvascular) of type 2 diabetes mellitus (T2DM) in the
      autonomous community of Madrid (Spain) (ACM). METHODS: The number of expected
      complications was obtained from a descriptive, cross-sectional study on a cohort
      of 3,268 patients with T2DM from the ACM. Cost of complications (?, 2012) was
      assessed both at hospitals and in primary care. The number of medical visits in
      primary care and drug treatment for complications were collected by a panel of 21
      physicians experienced in treatment of T2DM. Population and epidemiological data
      and healthcare costs were obtained from Spanish sources. Univariate sensitivity
      analyses were performed. RESULTS: It is estimated that there are 390,944 patients
      with T2DM in the ACM, and that they experience 172,406 and 212,283 macrovascular
      and microvascular complications respectively during their lifetimes. Mean cost of
      T2DM complications per patient is estimated at ? 4,121.54 (66% due to
      macrovascular complications). The economic impact of T2DM complications in the
      ACM would be ? 1,611 million (1,065 and 545 millions from macrovascular and
      microvascular complications respectively). The economic impact would range from ?
      1,249 and 2.509 million euro depending on T2DM prevalence. CONCLUSIONS:
      Complications of T2DM have a great health and economic impact in ACM.

PMID- 24440212
TI  - Influence of free fatty acids on glucose uptake in prostate cancer cells.
AB  - INTRODUCTION: The study focuses on the interaction between glucose and free fatty
      acids (FFA) in malignant human prostate cancer cell lines by an in vitro
      observation of uptake of fluoro-2-deoxy-D-glucose (FDG) and acetate. METHODS:
      Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated
      for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco's Modified Eagle's
      Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0-1.0
      mM). Then the cells were incubated with [(18)F]-FDG (1 MUCi/mL; 0.037 MBq/mL) in
      DMEM either in presence or absence of glucose and in presence of varying
      concentrations of palmitate for 1 h. Standardized procedures regarding cell
      counting and measuring for (18)F radioactivity were applied. Cell uptake studies
      with (14)C-1-acetate under the same conditions were performed on PC3 cells.
      RESULTS: In glucose containing media there was significantly increased FDG uptake
      after 24 h incubation in all cell lines, except DU145, when upper physiological
      levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells
      (15.11% vs. 3.94%/10(6) cells) was observed in media with 1.0 mM palmitate
      compared to media with no palmitate. The same tendency was observed in PC3 and
      CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant
      differences in FDG uptake after 24 h incubation were observed. The significant
      differences after 2 h incubation all pointed in the direction of increased FDG
      uptake when palmitate was added. Acetate uptake in PC3 cells was significantly
      lower when palmitate was added in glucose-free DMEM. No clear tendency when
      comparing FDG or acetate uptake in the same media at different time points of
      incubation was observed. CONCLUSIONS: Our results indicate a FFA dependent
      metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the
      true heterogeneity of the disease.

PMID- 24440213
TI  - Hepatic portal venous gas: an ominous sign of mesenteric ischemia.

PMID- 24440214
TI  - Increased risk of pancreatic adenocarcinoma after acute pancreatitis.
AB  - BACKGROUND & AIMS: Acute pancreatitis (AP) is often the initial presentation of
      pancreatic cancer (pancreatic adenocarcinoma [PaCa]). We evaluated the risk of
      PaCa after AP. METHODS: We performed a retrospective study of patients with AP
      who sought care in the Veterans Health Administration from 1998 through 2007. We
      excluded patients with pre-existing PaCa or recurrent AP and those who had the
      first episode of acute pancreatitis, from 1998 through 2000. RESULTS: Of 495,504
      patients with Veterans Health Administration inpatient and outpatient records,
      5720 were diagnosed with AP (1.15%) and 710 were diagnosed with PaCa (0.14%),
      from 2000 through 2007. Seventy-six patients had AP within 2 years before being
      diagnosed with PaCa (10.7% of all patients with cancer diagnosed during that
      period). The risk for PaCa was greatest in the first year after AP (14.5 per 1000
      patient-years) and then decreased rapidly. Risk for PaCa was negligible in
      patients <40 years old. The incidence of PaCa within the first year after AP was
      7.69 per 1000 patient-years in fifth decade of life and reached 28.67 after the
      seventh decade. Time to diagnosis of PaCa after AP was <=2 months for 34
      patients, 3-12 months for 35 patients, 13-24 months for 7 patients, and >24
      months for 10 patients. CONCLUSIONS: A significant number of patients with PaCa
      initially present with AP; the diagnosis of cancer is often delayed by up to 2
      years. We suggest that PaCa be routinely considered as a potential etiology of AP
      in patients >=40 years old.

PMID- 24440215
TI  - Reduced coffee consumption among individuals with primary sclerosing cholangitis
      but not primary biliary cirrhosis.
AB  - BACKGROUND & AIMS: Coffee consumption has been associated with decreased risk of
      liver disease and related outcomes. However, coffee drinking has not been
      investigated among patients with cholestatic autoimmune liver diseases, primary
      biliary cirrhosis (PBC), or primary sclerosing cholangitis (PSC). We investigated
      the relationship between coffee consumption and risk of PBC and PSC in a large
      North American cohort. METHODS: Lifetime coffee drinking habits were determined
      from responses to questionnaires from 606 patients with PBC, 480 with PSC, and
      564 healthy volunteers (controls). Patients (those with PBC or PSC) were compared
      with controls by using the Wilcoxon rank sum test for continuous variables and
      c(2) method for discrete variables. Logistic regression was used to analyze the
      estimate of the effects of different coffee parameters (time, frequency, and type
      of coffee consumption) after adjusting for age, sex, smoking status, and
      education level. RESULTS: Patients with PBC and controls did not differ in coffee
      parameters. However, 24% of patients with PSC had never drunk coffee compared
      with 16% of controls (P < .05), and only 67% were current drinkers compared with
      77% of controls (P < .05). Patients with PSC also consumed fewer lifetime cups
      per month (45 vs 47 for controls, P < .05) and spent a smaller percentage of
      their lifetime drinking coffee (46.6% vs 66.7% for controls, P < .05). These
      differences remained significant in a multivariate model. Among PSC patients with
      concurrent ulcerative colitis, coffee protected against proctocolectomy (hazard
      ratio, 0.34; P < .001). CONCLUSIONS: Coffee consumption is lower among patients
      with PSC, but not PBC, compared with controls.

PMID- 24440216
TI  - A prospective evaluation of undiagnosed joint hypermobility syndrome in patients
      with gastrointestinal symptoms.
AB  - BACKGROUND & AIMS: The Joint Hypermobility Syndrome (JHS) is a common connective
      tissue disorder characterized by joint hyperflexibility, dysautonomia, and
      chronic pain. Gastrointestinal (GI) symptoms are reported in JHS patients
      attending rheumatology clinics, but the prevalence and symptom pattern of
      previously undiagnosed JHS in GI clinics are unknown. METHODS: By using validated
      questionnaires, a prospective cross-sectional study in secondary care GI clinics
      estimated the prevalence of JHS in new consecutively referred patients, compared
      GI symptoms in patients with and without JHS, and by using multiple regression
      determined whether the burden of GI symptoms in JHS patients was dependent on
      chronic pain, autonomic, psychological, and medication related factors. A
      positive control group consisted of JHS patients referred from rheumatology
      clinics with GI symptoms (JHS-Rh). RESULTS: From 552 patients recruited, 180
      (33%) had JHS (JHS-G) and 372 did not (non-JHS-G). Forty-four JHS-Rh patients
      were included. JHS-G patients were more likely to be younger, female with poorer
      quality of life (P = .02) than non-JHS-G patients. After age and sex matching,
      heartburn (odds ratio [OR], 1.66; confidence interval [CI], 1.1-2.5; P = .01),
      water brash (OR, 2.02; CI, 1.3-3.1; P = .001), and postprandial fullness (OR,
      1.74; CI, 1.2-2.6; P = .006) were more common in JHS-G vs non-JHS-G. Many upper
      and lower GI symptoms increased with increasing severity of JHS phenotype. Upper
      GI symptoms were dependent on autonomic and chronic pain factors. CONCLUSIONS:
      JHS is common in GI clinics, with increased burden of upper GI and
      extraintestinal symptoms and poorer quality of life. Recognition of JHS will
      facilitate multidisciplinary management of GI and extra-GI manifestations.

PMID- 24440217
TI  - Shedding light on the value of advanced imaging in Barrett's esophagus.

PMID- 24440218
TI  - Can you hear me now? Frequent telephone encounters for management of patients
      with inflammatory bowel disease.

PMID- 24440219
TI  - Is there really anything new on dietary fiber in colonic diverticular disease?

PMID- 24440220
TI  - Concerns in defining risk factors for asymptomatic diverticulosis.

PMID- 24440221
TI  - Postoperative therapy with infliximab prevents long-term Crohn's disease
      recurrence.
AB  - BACKGROUND & AIMS: A previous randomized, placebo-controlled study showed that
      infliximab maintenance therapy prevented recurrence of Crohn's disease 1 year
      after an ileocolonic resection. We evaluated recurrence of Crohn's disease, on
      the basis of endoscopic examination and/or the need for additional surgical
      resection, beyond the first postoperative year. METHODS: In a prospective, open
      label, long-term follow-up study, 24 patients previously randomly assigned to
      receive infliximab for 1 year after an ileocolonic resection were given the
      option to continue, stop, or start infliximab therapy. The primary end point was
      the time to recurrence of Crohn's disease, on the basis of endoscopic evidence
      (endoscopic recurrence), from the initial assignment to postoperative infliximab
      or placebo. Secondary end points were rate of endoscopic recurrence, time to
      reoperation, and rate of surgical recurrence in relation to the total time on
      infliximab. RESULTS: All patients were followed for at least 5 years after
      surgery. Patients assigned to the infliximab group in the first year after
      surgery had a longer mean time to first endoscopic recurrence (1231 +/- 747 days)
      than patients originally assigned to the placebo group (460 +/- 121 days, P =
      .003). Colonoscopies identified Crohn's disease recurrence in 22.2% of patients
      who received long-term infliximab and in 93.9% of those not on infliximab (P <
      .0001). Compared with no infliximab, the adjusted rate ratio for being in
      endoscopic remission while on infliximab was 13.47 (95% confidence interval, 3.52
      61.53; P = .0001). Patients originally assigned to the infliximab group had a
      mean longer time to surgery (1798 +/- 359 days) than patients originally assigned
      to the placebo group (1058 +/- 529 days, P = .04). The rate of surgical
      recurrence (required additional surgical resection) was significantly lower among
      patients who received infliximab for most of the follow-up period than patients
      who received it for shorter periods (20.0% vs 64.3%, P = .047). CONCLUSIONS:
      Postoperative infliximab maintenance beyond 1 year prevents recurrence of Crohn's
      disease.

PMID- 24440222
TI  - Efficacy of combined jejunal and colonic fecal microbiota transplantation for
      recurrent Clostridium difficile Infection.
AB  - The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing;
      fecal microbiota transplantation (FMT) is an effective therapy. However, there
      have been no studies of the efficacy of a single session of combined enteral and
      colonic FMT or characterizations of changes in the microbiota between donors and
      recipients. We performed a study of 27 patients with RCDI who were given a fixed
      volume of processed fecal filtrate via enteroscopy and colonoscopy in a single
      session. Patients were closely monitored, and fecal samples were collected from 2
      patient-donor pairs for 16S rRNA analysis. All patients had reduced stool
      frequency, abdominal pain, white blood cell counts, and elimination of fecal C
      difficile toxin (P < .05). FMT increased microbial diversity, increasing
      proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of
      Enterobacteriaceae. FMT was associated with marked changes in the composition of
      fecal microbiota in 2 patients with RCDI. 

PMID- 24440223
TI  - Medical therapies used for low bone mineral density in patients with inflammatory
      bowel disease.

PMID- 24440224
TI  - Complete clogging by fungus ball: a rare complication of gastrostomy.

PMID- 24440225
TI  - Reply to about the electrophysiological basis of resting state networks.

PMID- 24440226
TI  - The effect of alcohol on cervical and ocular vestibular evoked myogenic
      potentials in healthy volunteers.
AB  - OBJECTIVE: We investigated the effect of alcohol on the cervical and ocular
      vestibular evoked myogenic potentials (cVEMPs and oVEMPs). As alcohol produces
      gaze-evoked nystagmus (GEN), we also tested the effect of nystagmus independent
      of alcohol by recording oVEMPs during optokinetic stimulation (OKS). METHODS: The
      effect of alcohol was tested in 14 subjects over multiple rounds of alcohol
      consumption up to a maximum breath alcohol concentration (BrAC) of 1.50/00 (mean
      0.970/00). The effect of OKS was tested in 11 subjects at 5, 10 and 15deg/sec.
      RESULTS: oVEMP amplitude decreased from baseline to the highest BrAC level by 27%
      (range 5-50%, P<0.001), but there was no significant effect on oVEMP latency or
      cVEMP amplitude or latency. There was a significant negative effect of OKS on
      oVEMP amplitude (16%, P=0.006). CONCLUSIONS: We found a selective effect of
      alcohol on oVEMP amplitude, but no effect on the cVEMP. Vertical nystagmus
      elicited by OKS reduced oVEMP amplitude. SIGNIFICANCE: Alcohol selectively
      affects oVEMP amplitude. Despite the effects of alcohol and nystagmus, both
      reflexes were reliably recorded in all subjects and conditions. An absent
      response in a patient affected by alcohol or nystagmus indicates a vestibular
      deficit.

PMID- 24440227
TI  - Temporal responses of C. elegans chemosensory neurons are preserved in behavioral
      dynamics.
AB  - Animals track fluctuating stimuli over multiple timescales during natural
      olfactory behaviors. Here, we define mechanisms underlying these computations in
      Caenorhabditis elegans. By characterizing neuronal calcium responses to rapidly
      fluctuating odor sequences, we show that sensory neurons reliably track stimulus
      fluctuations relevant to behavior. AWC olfactory neurons respond to multiple
      odors with subsecond precision required for chemotaxis, whereas ASH nociceptive
      neurons integrate noxious cues over several seconds to reach a threshold for
      avoidance behavior. Each neuron's response to fluctuating stimuli is largely
      linear and can be described by a biphasic temporal filter and dynamical model. A
      calcium channel mutation alters temporal filtering and avoidance behaviors
      initiated by ASH on similar timescales. A sensory G-alpha protein mutation
      affects temporal filtering in AWC and alters steering behavior in a way that
      supports an active sensing model for chemotaxis. Thus, temporal features of
      sensory neurons can be propagated across circuits to specify behavioral dynamics.

PMID- 24440229
TI  - The pivotal role played by lipocalin-2 in chronic inflammatory pain.
AB  - Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury,
      infection or other inflammatory stimuli. Based on the previously reported
      involvement of LCN2 in chemokine induction and in the recruitment of neutrophils
      at the sites of infection or tissue injury, we investigated the role of LCN2 in
      the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the
      complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2
      expression was strongly induced in the ipsilateral hindpaws, peaking at 12h after
      CFA injection and then gradually subsiding. In CFA-injected hindpaw tissues, LCN2
      and its receptor 24p3R were mainly expressed in infiltrating neutrophils and
      macrophages. CFA-induced thermal hyperalgesia and mechanical allodynia were
      significantly diminished in Lcn2-deficient mice compared to wild-type animals.
      Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF
      alpha, IL-1beta and MIP-2 in CFA-injected hindpaws, and spinal glial activation
      were markedly reduced by Lcn2 deficiency. An intraplantar injection of
      recombinant LCN2 protein induced thermal and mechanical hypersensitivities in
      naive mice, and this was accompanied by neutrophil and macrophage infiltration
      into the hindpaws and glial activation in the dorsal horn of the spinal cord.
      Taken together, our results show that inflammatory cell-derived LCN2 at the sites
      of inflammation plays important roles in central sensitization and the subsequent
      nociceptive behavior in the rodent model of chronic inflammatory pain. 

PMID- 24440230
TI  - Reduced post-natal versus pre-natal incidence of bent long bones and scapulae in
      a preliminary investigation using the Han Wistar rat.
AB  - There is a "chondrodystrophy" syndrome in the Han Wistar rat fetus that manifests
      as characteristic skeletal abnormalities such as bent and/or short long bones,
      and is classified as permanent detrimental abnormalities (major malformations).
      This pilot study investigated whether these defects resolve after birth. Han
      Wistar rats were dosed during organogenesis either with vehicle or test article.
      Examination of gestation day 20 fetuses showed a slightly increased incidence
      (11%; 11/101) of skeletal abnormalities in the high dose fetuses compared with 6%
      (4/67) in control fetuses, whereas no skeletal abnormalities were present in the
      205 pups examined on post-natal day 21. The probability of having zero litters
      containing pups with skeletal abnormalities was p<0.0000001. This very low
      probability suggests that these defects recover by weaning and supports the
      hypothesis that these fetal findings in the Han Wistar are probably not permanent
      abnormalities and therefore are potentially reclassifiable as minor
      malformations. 

PMID- 24440228
TI  - Insulin/IGF1 signaling inhibits age-dependent axon regeneration.
AB  - The ability of injured axons to regenerate declines with age, yet the mechanisms
      that regulate axon regeneration in response to age are not known. Here we show
      that axon regeneration in aging C. elegans motor neurons is inhibited by the
      conserved insulin/IGF1 receptor DAF-2. DAF-2's function in regeneration is
      mediated by intrinsic neuronal activity of the forkhead transcription factor DAF
      16/FOXO. DAF-16 regulates regeneration independently of lifespan, indicating that
      neuronal aging is an intrinsic, neuron-specific, and genetically regulated
      process. In addition, we found that DAF-18/PTEN inhibits regeneration
      independently of age and FOXO signaling via the TOR pathway. Finally, DLK-1, a
      conserved regulator of regeneration, is downregulated by insulin/IGF1 signaling,
      bound by DAF-16 in neurons, and required for both DAF-16- and DAF-18-mediated
      regeneration. Together, our data establish that insulin signaling specifically
      inhibits regeneration in aging adult neurons and that this mechanism is
      independent of PTEN and TOR. 

PMID- 24440231
TI  - Delayed reproductive development in pubertal male rats exposed to the
      hypolipemiant agent rosuvastatin since prepuberty.
AB  - Dyslipidemias are frequently found in children due to obesity, bad eating habits
      and the lack of physical exercises. Rosuvastatin acts as an HMG-CoA reductase
      inhibitor, decreasing total cholesterol and triglycerides. This study aimed to
      investigate initial sexual development and morphological aspect of the testis and
      epididymis in juvenile rats exposed to rosuvastatin since pre-puberty. Three
      groups were formed with newly weaned rats: control, whose rats received saline
      solution 0.9%, rosuvastatin at doses of 3 or 10 mg/kg daily by gavage, since post
      natal day 21 until puberty onset. In the rosuvastatin-treated groups, the results
      demonstrated a trend toward a decrease in testosterone concentration, but below
      the significance level, as well as delays in both the age of puberty onset and in
      epididymal development. There were also testicular alterations that might be
      related to delayed puberty and decrease of serum testosterone. In conclusion,
      rosuvastatin administration to juvenile rats not only delayed puberty onset and
      epididymal development, but also impaired testicular and epididymal morphology.

PMID- 24440232
TI  - Evaluation of homo- and hetero-functionally activated glass surfaces for
      optimized antibody arrays.
AB  - Antibody arrays hold great promise for biomedical applications, but they are
      typically manufactured using chemically functionalized surfaces that still
      require optimization. Here, we describe novel hetero-functionally activated glass
      surfaces favoring oriented antibody binding for improved performance in protein
      microarray applications. Antibody arrays manufactured in our facility using the
      functionalization chemistries described here proved to be reproducible and stable
      and also showed good signal intensities. As a proof-of-principle of the glass
      surface functionalization protocols described in this article, we built antibody
      based arrays functionalized with different chemistries that enabled the
      simultaneous detection of 71 human leukocyte membrane differentiation antigens
      commonly found in peripheral blood mononuclear cells. Such detection is specific
      and semi-quantitative and can be performed in a single assay under native
      conditions. In summary, the protocol described here, based on the use of antibody
      array technology, enabled the concurrent detection of a set of membrane proteins
      under native conditions in a specific, selective, and semi-quantitative manner
      and in a single assay. 

PMID- 24440234
TI  - Inhibition of grade dependent autophagy in urothelial carcinoma increases cell
      death under nutritional limiting condition and potentiates the cytotoxicity of
      chemotherapeutic agent.
AB  - PURPOSE: We evaluated the status of autophagy in different grades of urothelial
      carcinoma and explored autophagy modulators as a potential adjunctive therapeutic
      agent for urothelial carcinoma. MATERIALS AND METHODS: The study was performed in
      tumor tissue from patients with low and high grade urothelial carcinoma, in
      normal urothelial tissue and in the T24 cell line. Autophagic vesicles and the
      expression of various autophagic proteins were studied in tissue samples by
      transmission electron microscopy and Western blot, respectively. The effect of
      autophagy induction and inhibition was evaluated by measuring AMPK and mTOR
      expression, cell viability and mitochondrial membrane potential. The therapeutic
      implication of autophagy was studied using cisplatin alone or combined with an
      autophagy inhibitor. RESULTS: High grade urothelial carcinoma showed a higher
      number of autophagic vesicles and significantly higher expression of autophagic
      proteins. Upon starvation cells cultured from high and low grade urothelial
      carcinoma demonstrated significant autophagy induction associated with AMPK
      activation and mTOR inhibition. AMPK inhibition decreased the autophagic response
      and increased cell death. Autophagy inhibition by wortmannin, 3-methyladenine and
      chloroquine increased mitochondrial hypopolarization as well as caspase-9 and 3
      dependent cell death. Combined treatment with cisplatin and an autophagy
      inhibitor resulted in greater cell death than cisplatin treatment alone.
      CONCLUSIONS: Autophagy is related to urothelial carcinoma grade and regulated via
      the AMPK pathway for tumor cell survival. Autophagy inhibition leads to cancer
      cell death through an intrinsic apoptotic pathway. The potential application of
      autophagy inhibitors as an adjunct to chemotherapy for urothelial carcinoma must
      be explored.

PMID- 24440233
TI  - Characterization of intact N- and O-linked glycopeptides using higher energy
      collisional dissociation.
AB  - Simultaneous elucidation of the glycan structure and the glycosylation site are
      needed to reveal the biological function of protein glycosylation. In this study,
      we employed a recent type of fragmentation termed higher energy collisional
      dissociation (HCD) to examine fragmentation patterns of intact glycopeptides
      generated from a mixture of standard glycosylated proteins. The normalized
      collisional energy (NCE) value for HCD was varied from 30 to 60% to evaluate the
      optimal conditions for the fragmentation of peptide backbones and
      glycoconjugates. Our results indicated that HCD with lower NCE values
      preferentially fragmented the sugar chains attached to the peptides to generate a
      ladder of neutral loss of monosaccharides, thereby enabling the putative glycan
      structure characterization. In addition, detection of the oxonium ions enabled
      unambiguous differentiation of glycopeptides from non-glycopeptides. In contrast,
      HCD with higher NCE values preferentially fragmented the peptide backbone and,
      thus, provided information needed for confident peptide identification. We
      evaluated the HCD approach with alternating NCE parameters for confident
      characterization of intact N- and O-linked glycopeptides in a single liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis. In addition, we
      applied a novel data analysis pipeline, so-called GlycoFinder, to form a basis
      for automated data analysis. Overall, 38 unique intact glycopeptides
      corresponding to eight glycosylation sites (six N-linked and two O-linked sites)
      were confidently identified from a standard protein mixture. This approach
      provided concurrent characterization of both the peptide and the glycan, thereby
      enabling comprehensive structural characterization of glycoproteins in a single
      LC-MS/MS analysis. 

PMID- 24440235
TI  - Influence of magnetic resonance imaging in the decision to preserve or resect
      neurovascular bundles at robotic assisted laparoscopic radical prostatectomy.
AB  - PURPOSE: We evaluated the accuracy of preoperative multiparametric 3.0-T magnetic
      resonance imaging for local staging of prostate cancer and its influence in the
      decision to preserve neurovascular bundles at robotic assisted laparoscopic
      radical prostatectomy. MATERIALS AND METHODS: The study included 353 patients who
      had confirmed prostate cancer and underwent preoperative magnetic resonance
      imaging and robotic assisted laparoscopic radical prostatectomy between 2008 and
      2011. The extent of neurovascular bundle sparing was initially determined on the
      basis of the clinical information and the nerve sparing surgical plan was
      reevaluated after review of the magnetic resonance imaging report. The value of
      preoperative magnetic resonance imaging in the prediction of extracapsular
      extension and in the decision of surgical plan according to D'Amico risk
      classification was analyzed. RESULTS: The magnetic resonance imaging performed
      correct staging, over staging and under staging in 261 (73.9%), 43 (12.2%), and
      49 (13.9%) patients, respectively. After review of the magnetic resonance imaging
      reports, the initial surgical plan was not changed in 260 patients (74%) and was
      changed in 93 patients (26%). Robotic assisted laparoscopic radical prostatectomy
      was changed to a more preservable neurovascular bundle sparing procedure in 53
      patients (57%) and changed to a more aggressive neurovascular bundle resecting
      procedure in 40 patients (43%). For the patients with a change to more
      conservative surgery, the appropriateness was 91%. The sensitivity of magnetic
      resonance imaging in predicting extracapsular extension showed a tendency to
      increase from low to high risk groups (33%, 46%, 80%, respectively, p <0.001). In
      intermediate and high risk groups, there was a surgical plan change in 40
      patients (of 129, 31%) and 27 patients (of 67, 40%), respectively. CONCLUSIONS:
      Preoperative magnetic resonance imaging significantly improves the decision
      making to preserve or resect the neurovascular bundle at robotic assisted
      laparoscopic radical prostatectomy, which lacks haptic feedback.

PMID- 24440236
TI  - Early removal of urethral catheter with suprapubic tube drainage versus urethral
      catheter drainage alone after robot-assisted laparoscopic radical prostatectomy.
AB  - PURPOSE: Retrospective single institution data suggest that postoperative pain
      after robot-assisted laparoscopic radical prostatectomy is decreased by early
      removal of the urethral catheter with suprapubic tube drainage. In a randomized
      patient population we determined whether suprapubic tube drainage with early
      urethral catheter removal would improve postoperative pain compared with urethral
      catheter drainage alone. MATERIALS AND METHODS: Men with a body mass index of
      less than 40 kg/m(2) who had newly diagnosed prostate cancer and elected robot
      assisted laparoscopic radical prostatectomy were included in analysis. Block
      randomization by surgeon was used and randomization assignment was done after
      completing the urethrovesical anastomosis. In patients assigned to suprapubic
      tube drainage the urethral catheter was removed on postoperative day 1 and all
      catheters were removed on postoperative day 7. Visual analog pain scale and
      satisfaction questionnaires were administered on postoperative days 0, 1 and 7.
      RESULTS: A total of 29 patients were randomized to the urethral catheter vs 29 to
      the suprapubic tube plus early urethral catheter removal at the time of interim
      futility analysis. Mean visual analog pain scale scores did not differ between
      the groups at any time point and a similar percent of patients cited the catheter
      as the greatest bother with nonsignificant differences in treatment related
      satisfaction. Complications during postoperative week 1 did not vary between the
      groups. Based on interim results the trial was terminated due to lack of effect.
      CONCLUSIONS: Patients randomized to suprapubic tube vs urethral catheter drainage
      for the week after prostatectomy had similar pain, catheter related bother and
      treatment related satisfaction in the perioperative period. We no longer
      routinely offer suprapubic tube drainage with early urethral catheter removal at
      our institution.

PMID- 24440237
TI  - Vasectomy induces oxidative stress and up-regulates the expression of
      peroxiredoxins in mouse testis in short and early periods after surgery.
AB  - PURPOSE: We investigated oxidative damage caused by and antioxidant responses to
      peroxiredoxins in the mouse testis at different time points after vasectomy.
      MATERIALS AND METHODS: Mice were divided into a sham operated control group and a
      vasectomized group. Testicular samples were collected 2 to 120 days
      postoperatively. Histology and cell apoptosis were evaluated by hematoxylin and
      eosin staining, and TUNEL assay, respectively. Oxidative damage was determined
      using a commercial malondialdehyde kit. The expression of peroxiredoxin and other
      antioxidant enzyme mRNAs was detected by reverse transcriptase-polymerase chain
      reaction. Western blot and immunohistochemistry were performed to examine
      peroxiredoxin protein expression. RESULTS: Histology revealed severe damage in
      vasectomized testes with high malondialdehyde levels. The alteration in
      malondialdehyde was in parallel with the process of histological injury and
      apoptosis. Germ cell apoptosis developed in a time dependent and cell specific
      manner. The expression of peroxiredoxin 1, 2 and 3, especially peroxiredoxin 2,
      was significantly up-regulated at the mRNA and protein levels in the testis after
      vasectomy, which subsequently ameliorated testicular damage toward the control
      level. In addition, other related antioxidant enzymes, such as Cat and Sod3,
      showed decreased expression at the mRNA level in vasectomized testes.
      CONCLUSIONS: This study shows that vasectomy induces oxidative stress in the
      mouse testis in the short-term early period after surgery, resulting in
      histological injury and germ cell apoptosis. Peroxiredoxins may have important
      roles as antioxidant defenses in vasectomized testis and provide new prevention
      and therapy alternatives for testicular damage after vasectomy.

PMID- 24440238
TI  - Transcriptome de novo assembly sequencing and analysis of the toxic
      dinoflagellate Alexandrium catenella using the Illumina platform.
AB  - In this article, high-throughput de novo transcriptomic sequencing was performed
      in Alexandrium catenella, which provided the first view of the gene repertoire in
      this dinoflagellate based on next-generation sequencing (NGS) technologies. A
      total of 118,304 unigenes were identified with an average length of 673bp (base
      pair). Of these unigenes, 77,936 (65.9%) were annotated with known proteins based
      on sequence similarities, among which 24,149 and 22,956 unigenes were assigned to
      gene ontology categories (GO) and clusters of orthologous groups (COGs),
      respectively. Furthermore, 16,467 unigenes were mapped onto 322 pathways using
      the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG). We also
      detected 1143 simple sequence repeats (SSRs), in which the tri-nucleotide repeat
      motif (69.3%) was the most abundant. The genetic facts and significance derived
      from the transcriptome dataset were suggested and discussed. All four core
      nucleosomal histones and linker histones were detected, in addition to the
      unigenes involved in histone modifications.190 unigenes were identified as being
      involved in the endocytosis pathway, and clathrin-dependent endocytosis was
      suggested to play a role in the heterotrophy of A. catenella. A conserved 22-nt
      spliced leader (SL) was identified in 21 unigenes which suggested the existence
      of trans-splicing processing of mRNA in A. catenella. 

PMID- 24440239
TI  - Spectrum and distribution of CFTR gene mutations in asthma and chronic
      pancreatitis cases of North Indian population.
AB  - BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) gene
      accounts for an autosomal recessive condition called cystic fibrosis (CF). In the
      Indian subcontinent, CF and its related diseases are under-diagnosed by the
      medical community due to poor knowledge of the disease and its confounding
      diagnosis, and also due to poor medical facilities available for these patients,
      thus causing an increased infant mortality rate with a low life expectancy in
      general. The aim of the study was to document the spectrum and distribution of
      CFTR mutations in controls, asthma and chronic pancreatitis cases of North India.
      METHODS: A total of 800 subjects including 400 controls, 250 asthma cases and150
      chronic pancreatitis cases were analyzed for 6 mutations (F508del, G542X, G551D,
      R117H, W1282X, and S549N) and IVS8 Tn polymorphism. RESULTS: Out of 800 subjects,
      18% [asthma - 24% (n=250), CP - 29.33% (n=150) cases and controls - 9.3% (n=400)]
      were positive for heterozygous mutation, 0.8% of the (n=250) asthmatic cases
      (n=250) were homozygous for IVS8 T5 polymorphism while no subjects were found
      positive for W1282X mutation. T5 polymorphism was more common in asthmatic cases
      while F508del mutation in chronic pancreatitis cases. The carrier frequency of
      F508del, G542X, G551D, R117H, S549N and T5 was 0.015, 0.025, 0.02, 0.005, 0.005,
      and 0.022 respectively. The cumulative carrier frequency was 0.093. CONCLUSION:
      CFTR mutations were underestimated in Indian population. The present study will
      serve in establishment of genetic screening and prenatal setup for Indian
      population.

PMID- 24440240
TI  - Diagnosis and therapeutic monitoring of inborn errors of creatine metabolism and
      transport using liquid chromatography-tandem mass spectrometry in urine, plasma
      and CSF.
AB  - Biochemical detection of inborn errors of creatine metabolism or transport relies
      on the analysis of three main metabolites in biological fluids: guanidinoacetate
      (GAA), creatine (CT) and creatinine (CTN). Unspecific clinical presentation of
      the diseases might be the cause that only few patients have been diagnosed so
      far. We describe a LC-MS/MS method allowing fast and reliable diagnosis by
      simultaneous quantification of GAA, CT and CTN in urine, plasma and cerebrospinal
      fluid (CSF) and established reference values for each material. For
      quantification deuterated stable isotopes of each analyte were used as internal
      standards. GAA, CT and CTN were separated by reversed-phase HPLC. The
      characterization was carried out by scanning the ions of each compound by
      negative ion tandem mass spectrometry. Butylation is needed to achieve sufficient
      signal intensity for GAA and CT but it is not useful for analyzing CTN. The assay
      is linear in a broad range of analyte concentrations usually found in urine,
      plasma and CSF. Comparison of the "traditional" cation-exchange chromatography
      and LC-MS/MS showed proportional differences but linear relationships between the
      two methods. The described method is characterized by high speed and linearity
      over large concentration ranges comparable to other published LC-MS methods but
      with higher sensitivity for GAA and CT. In addition, we present the largest
      reference group ever published for guanidino compounds in all relevant body
      fluids. Therefore this method is applicable for high-throughput approaches for
      diagnosis and follow-up of inborn errors of creatine metabolism and transport.

PMID- 24440241
TI  - A novel MYB transcription factor, GmMYBJ1, from soybean confers drought and cold
      tolerance in Arabidopsis thaliana.
AB  - MYB transcription factors play important roles in the regulation of plant growth,
      developmental metabolism and stress responses. In this study, a new MYB
      transcription factor gene, GmMYBJ1, was isolated from soybean [Glycine max (L.)].
      The GmMYBJ1 cDNA is 1296bp in length with an open reading frame (ORF) of 816 bp
      encoding for 271 amino acids. The amino acid sequence displays similarities to
      the typical R2R3 MYB proteins reported in other plants. Transient expression
      analysis using the GmMYBJ1-GFP fusion gene in onion epidermal cells revealed that
      the GmMYBJ1 protein is targeted to the nucleus. Quantitative RT-PCR analysis
      demonstrated that GmMYBJ1 expression was induced by abiotic stresses, such as
      drought, cold, salt and exogenous abscisic acid (ABA). Compared to wild-type (WT)
      plants, transgenic Arabidopsis overexpressing GmMYBJ1 exhibited an enhanced
      tolerance to drought and cold stresses. These results indicate that GmMYBJ1 has
      the potential to be utilized in transgenic breeding lines to improve abiotic
      stress tolerance.

PMID- 24440242
TI  - Identification of a Bombyx mori gene encoding small heat shock protein BmHsp27.4
      expressed in response to high-temperature stress.
AB  - Elucidating the mechanisms underlying the response and resistance to high
      temperature stress in the Lepidoptera is essential for understanding the effect
      of high-temperature on the regulation of gene expression. A tag
      (CATGAACGTGAAGAGATTCAG) matching the predicted gene BGIBMGA005823-TA in SilkDB
      identified the most significant response to high-temperature stress in a screen
      of the heat-treated digital gene expression library of Bombyx mori (B. mori)
      (Unpublished data). BLAST and RACE showed that the gene is located on chromosome
      5 and has an open reading frame (ORF) of 741bp. Phylogenetic analysis found that
      B. mori small heat shock protein 27.4 (BmHSP27.4) is in an evolutionary branch
      separate from other small heat shock proteins. Expression analysis showed that
      BmHsp27.4 is highly expressed in brain, eyes and fat bodies in B. mori. Its mRNA
      level was elevated at high-temperature and this increase was greater in females.
      The ORF without the signal peptide sequence was cloned into vector pET-28a(+),
      transformed and over-expressed in Escherichia coli Rosetta (DE3). Western
      blotting and immunofluorescence analysis with a polyclonal antibody, confirmed
      that the level of protein BmHSP27.4 increased at a high-temperature, in
      accordance with its increased mRNA level. In this study, BmHsp27.4 was identified
      as a novel B. mori gene with an important role in response to high-temperature
      stress.

PMID- 24440243
TI  - AT2R -1332 G:A polymorphism and its interaction with AT1R 1166 A:C, ACE I/D and
      MMP-9 -1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia.
AB  - The possible association of angiotensin type 2 receptor (AT2R) -1332 G:A
      polymorphism with susceptibility to preeclampsia was studied in 252 women
      consisted of 155 women with preeclampsia and 97 healthy pregnant women. Also, the
      interaction of this polymorphism with angiotensin type 1 receptor (AT1R) 1166
      A:C, angiotensin converting enzyme insertion/deletion (ACE I/D) and also with
      matrix metalloproteinase-9 (MMP-9) -1562 C:T polymorphism was investigated. The
      AT2R -1332 G:A polymorphism was detected using PCR-RFLP method. Significantly
      higher frequencies of GG+GA genotype and G allele of AT2R were observed in mild
      (80.2%, p=0.003 and 47.5%, p=0.012, respectively) and severe (77.8%, p=0.034 and
      48.1%, p=0.026, respectively) preeclampsia compared to controls (60.8% and 35.1%,
      respectively). The presence of G allele was associated with 1.69-fold increased
      risk of preeclampsia (p=0.005). In severe preeclamptic women, systolic and
      diastolic blood pressures in the presence of GG+GA genotype were significantly
      higher compared to those in the presence of AA genotype. The concomitant presence
      of both alleles of AT2R G and AT1R C was associated with 1.3 times increased risk
      of mild preeclampsia (p=0.03). There was an interaction between AT2R G and ACE D
      alleles that significantly increased the risk of mild and severe preeclampsia by
      1.38- and 1.3-fold, respectively. Also, interaction between MMP-9 T and AT2R G
      alleles increased the risk of severe preeclampsia 1.39-fold (p=0.028). Our study
      demonstrated that the G allele of AT2R -1332 G:A polymorphism is associated with
      an increased risk of preeclampsia. Also, epistatic interaction of G allele and
      each allele of the AT1R C, ACE D and MMP-9 T was associated with the risk of
      preeclampsia. Our findings suggest that the renin-angiotensin system (RAS)
      variants and gene-gene interactions affect the risk of preeclampsia.

PMID- 24440244
TI  - Geographic variation within a tandemly repeated mitochondrial DNA D-loop region
      of a North American freshwater fish, Pylodictis olivaris.
AB  - The present study reports the distribution of a 35-bp mitochondrial DNA (mtDNA) D
      loop tandemly repeated sequence in the populations of a North American freshwater
      catfish, Pylodictis olivaris, and the important role of a past geological event
      in the phylogeographic pattern of this species. A total of 330 individuals of
      flathead catfish, representing 34 drainages throughout the species' native range
      in the United States, were collected. While more than 70% of individuals sampled
      from the Southeastern Gulf Coast drainages were characterized by the presence of
      a 35-bp mtDNA D-loop tandem repeat proximal to the 5' end, more than 95% of
      samples from the Mississippi River and its tributaries, as well as from the
      drainages of the Southwest Gulf Coast region, lack this tandem repeat.
      Concomitantly, phylogenetic analyses revealed the existence of two distinct
      matrilineal lineages (lineage I and II) of P. olivaris, which were estimated to
      have diverged from a common ancestor sometime between 0.70 and 2.05myr ago. While
      one lineage is comprised of samples from the Mississippi River and its
      tributaries and rivers draining to the Southwest Gulf Coast, the other lineage is
      comprised of samples from the Southeastern Gulf Coast drainages. Each lineage
      also has two sub-lineages, which also showed geographic specificity. 

PMID- 24440245
TI  - Effect of dry period length and dietary energy source on energy balance, milk
      yield, and milk composition of dairy cows.
AB  - The objective of this study was to evaluate the effects of dry period length and
      dietary energy source in early lactation on milk production, feed intake, and
      energy balance (EB) of dairy cows. Holstein-Friesian dairy cows (60 primiparous
      and 108 multiparous) were randomly assigned to dry period lengths (0, 30, or 60
      d) and early lactation ration (glucogenic or lipogenic), resulting in a 3 * 2
      factorial design. Rations were isocaloric and equal in intestinal digestible
      protein. The experimental period lasted from 8 wk prepartum to 14 wk postpartum
      and cows were monitored for milk yield, milk composition, dry matter intake
      (DMI), energy balance, and milk fat composition. Prepartum average milk yield for
      60 d precalving was 13.8 and 7.7 +/- 0.5 kg/d for cows with a 0- and 30-d dry
      period, respectively. Prepartum DMI and energy intake were greater for cows
      without a dry period and 30-d dry period, compared with cows with a 60-d dry
      period. Prepartum EB was greater for cows with a 60-d dry period. Postpartum
      average milk yield until wk 14 was lower for cows without a dry period and a 30-d
      dry period, compared with cows with a 60-d dry period (32.7, 38.7, and 43.3 +/-
      0.7 kg/d for 0-, 30-, and 60-d dry period, respectively). Postpartum DMI did not
      differ among treatments. Postpartum EB was greater for cows without a dry period
      and a 30-d dry period, compared with cows with a 60-d dry period. Young cows
      (parity 2) showed a stronger effect of omission of the dry period, compared with
      a 60-d dry period, on additional milk precalving (young cows: 15.1 kg/d; older
      cows: 12.0 kg/d), reduction in milk yield postcalving (young cows: 28.6 vs. 34.8
      kg/d; older cows: 41.8 vs. 44.1 kg/d), and improvement of the EB postcalving
      (young cows: 120 vs. -93 kJ/kg(0.75).d; older cows: -2 vs. -150 kJ/kg(0.75).d.
      Ration did not affect milk yield and DMI, but a glucogenic ration tended to
      reduce milk fat content and increased EB, compared with a more lipogenic ration.
      Reduced dry period length (0 and 30 d) increased the proportion of short- and
      medium-chain fatty acids in milk fat and omitting the dry period decreased the
      proportion of long-chain fatty acids in milk fat. In conclusion, shortening and
      omitting the dry period shifts milk yield from the postpartum to the prepartum
      period; this results in an improvement of the EB in early lactation. An increased
      energy status after a short dry period can be further improved by feeding a more
      glucogenic ration in early lactation.

PMID- 24440246
TI  - Ration formulations containing reduced-fat dried distillers grains with solubles
      and their effect on lactation performance, rumen fermentation, and intestinal
      flow of microbial nitrogen in Holstein cows.
AB  - Sixteen multiparous lactating Holstein cows were used in 2 experiments to
      evaluate the effects of reduced-fat dried distillers grains with solubles (RFDG)
      on milk production, rumen fermentation, intestinal microbial N flow, and total
      tract nutrient digestibility. In experiment 1, RFDG was fed at 0, 10, 20, or 30%
      of diet dry matter (DM) to 12 noncannulated Holstein cows (mean +/- standard
      deviation: 89 +/- 11 d in milk and 674 +/- 68.2 kg of body weight) to determine
      effects on milk production. In experiment 2, the same diets were fed to 4
      ruminally and duodenally cannulated Holstein cows (mean +/- standard deviation:
      112 +/- 41 d in milk; 590 +/- 61.14 kg of body weight) to evaluate the effects on
      rumen fermentation, intestinal flow of microbial N, and total-tract nutrient
      digestibility. In both experiments, cows were randomly assigned to 4 * 4 Latin
      squares over 21-d periods. Treatments (DM basis) were (1) control (0% RFDG), (2)
      10% RFDG, (3) 20% RFDG, and (4) 30% RFDG. Feed intake and milk yield were
      recorded daily. In both experiments, milk samples were collected on d 19 to 21 of
      each period for analysis of milk components. In experiment 2, ruminal pH was
      measured; samples of rumen fluid, duodenal digesta, and feces were collected on d
      18 to 21. Microbial N was estimated by using purines and DNA as microbial
      markers. Milk yield was not affected by treatment and averaged 34.0 +/- 1.29 kg/d
      and 31.4 +/- 2.81 kg/d in experiments 1 and 2, respectively. Percentage of milk
      protein tended to increase in experiment 1; estimates were 3.08, 3.18, 3.15, and
      3.19 +/- 0.06% when RFDG increased from 0 to 30% in the diets. However, milk
      protein concentration was not affected in experiment 2 and averaged 3.02 +/-
      0.07%. Percentage of milk fat was not affected and averaged 3.66 +/- 0.05% and
      3.25 +/- 0.14% in experiments 1 and 2, respectively. Total ruminal volatile fatty
      acids and ammonia concentrations were not affected by treatment and averaged
      135.18 +/- 6.45 mM and 18.66 +/- 2.32 mg/dL, respectively. Intestinal microbial N
      flow was not affected by treatment; however, purines yielded higher estimates of
      flow compared with DNA markers. When averaged across treatments, intestinal flow
      of microbial N was 303 and 218 +/- 18 g of N/d, using purines and DNA as the
      markers. Dry matter, organic matter, neutral detergent fiber, and nonfiber
      carbohydrate digestibility tended to increase with increasing inclusion of RFDG.
      Results from these experiments indicate that dairy rations can be formulated to
      include up to 30% RFDG while maintaining lactation performance, volatile fatty
      acids concentration, and intestinal supply of microbial N.

PMID- 24440247
TI  - Rumen bacterial community evaluated by 454 pyrosequencing and terminal
      restriction fragment length polymorphism analyses in dairy sheep fed marine
      algae.
AB  - Developing novel strategies to increase the content of bioactive unsaturated
      fatty acids (FA) in ruminant-derived products requires a deeper understanding of
      rumen biohydrogenation and bacteria involved in this process. Although high
      throughput pyrosequencing may allow for a great coverage of bacterial diversity,
      it has hardly been used to investigate the microbiology of ruminal FA metabolism.
      In this experiment, 454 pyrosequencing and a molecular fingerprinting technique
      (terminal restriction fragment length polymorphism; T-RFLP) were used
      concurrently to assess the effect of diet supplementation with marine algae (MA)
      on the rumen bacterial community of dairy sheep. Eleven lactating ewes were
      divided in 2 lots and offered a total mixed ration based on alfalfa hay and
      concentrate (40:60), supplemented with 0 (control) or 8 (MA) g of MA/kg of dry
      matter. After 54 d on treatments, animals were slaughtered and samples of rumen
      content and fluid were collected separately for microbial analysis.
      Pyrosequencing yielded a greater coverage of bacterial diversity than T-RFLP and
      allowed the identification of low abundant populations. Conversely, both
      molecular approaches pointed to similar conclusions and showed that relevant
      changes due to MA addition were observed within the major ruminal phyla, namely
      Bacteroidetes, Firmicutes, and Proteobacteria. Decreases in the abundance of
      unclassified Bacteroidales, Porphyromonadaceae, and Ruminococcaceae and increases
      in as-yet uncultured species of the family Succinivibrionaceae, might be related
      to a potential role of these groups in different pathways of rumen FA metabolism.
      Diet supplementation with MA, however, had no effect on the relative abundance of
      Butyrivibrio and Pseudobutyrivibrio genera. In addition, results from both 454
      pyrosequencing and T-RFLP indicate that the effect of MA was rather consistent in
      rumen content or fluid samples, despite inherent differences between these
      fractions in their bacterial composition.

PMID- 24440248
TI  - Biofilm-producing ability of Staphylococcus aureus isolates from Brazilian dairy
      farms.
AB  - This study aimed to investigate the in silico biofilm production ability of
      Staphylococcus aureus strains isolated from milking parlor environments on dairy
      farms from Sao Paulo, Brazil. The Staph. aureus isolates were obtained from 849
      samples collected on dairy farms, as follows: milk from individual cows with
      subclinical mastitis or history of the disease (n=220); milk from bulk tank
      (n=120); surfaces of milking machines and utensils (n=389); and milk handlers
      (n=120). Thirty-one Staph. aureus isolates were obtained and categorized as
      pulsotypes by pulsed-field gel electrophoresis and submitted to assays for
      biofilm formation on polystyrene, stainless steel, rubber, and silicone surfaces.
      Fourteen (45.2%) pulsotypes were considered producers of biofilm on the
      polystyrene microplate assay, whereas 13 (41.9%) and 12 (38.7%) pulsotypes were
      biofilm producers on stainless steel and rubber, respectively. None of the
      pulsotypes evaluated produced biofilms on silicone. Approximately 45% of Staph.
      aureus pulsotypes isolated from different sources on dairy farms showed the
      ability to produce biofilms in at least one assay, indicating possible
      persistence of this pathogen in the milking environment. The potential
      involvement of Staph. aureus in subclinical mastitis cases and its occurrence in
      milk for human consumption emphasize the need to improve hygiene practices to
      prevent biofilm formation on the farms studied. 

PMID- 24440249
TI  - Technical note: Evaluation of markers for estimating duodenal digesta flow and
      ruminal digestibility: Acid detergent fiber, sulfuric acid detergent lignin, and
      n-alkanes.
AB  - The amount of digesta flowing to the duodenum is a relevant measurement for the
      evaluation of nutrient supply to ruminants, which is usually estimated in animals
      fitted with a duodenal T-type cannula using internal or external markers. This
      study evaluated acid detergent fiber (ADF) compared with external (C32n-alkane)
      and internal [sulfuric acid lignin (ADL) and n-alkanes C31 and C33] markers for
      estimating duodenal flow and(or) ruminal digestibility of dry matter (DM) in
      cattle and sheep. In the first assay, 4 duodenally cannulated Holstein steers
      housed in metabolism cages, dosed with C32n-alkane, and fed Avena strigosa plus
      concentrate and increasing levels of tannin extract to reduce ruminal
      digestibility, were used in a Latin square design. The mobile-bag technique was
      used to measure the intestinal disappearance of ADL and ADF from forage (Avena
      strigosa, Pennisetum purpureum, Cynodon dactylon, and Medicago sativa) and
      concentrate (corn grain, soybean meal, and sunflower meal) samples that were
      previously incubated in the rumen of additional fistulated steer for 12, 24, 36,
      or 48 h. The ADF concentration in residues recovered in the feces was strongly
      related to the ADF concentration in residues at the duodenum (R(2)=0.93, standard
      deviation=30.0, n=901). This relationship showed a lower precision for ADL
      fraction (R(2)=0.88, standard deviation=12.6, n=590). In a second assay, duodenal
      flow and ruminal DM digestibility were calculated from the duodenal and fecal
      concentration of either marker. We observed a significant effect of marker type
      on ruminal DM digestibility values, and the effect of tannin treatments was
      observed only when ADF or ADL was used as the marker. The lowest residual error
      was obtained for ADF. Ruminal DM digestibility was, on average, higher for C31
      and C(33)n-alkanes, and the use of dosed C(32)n-alkane resulted in a negative
      value. In the third assay, a data set of 235 individual observations was compiled
      from digestibility trials to compare ADF and ADL as markers for estimating
      duodenal digesta flow in wethers (n=204) and cattle (n=31). We observed a strong
      relationship between markers (R(2)=0.84 in sheep and R(2)=0.88 in cattle), but
      variance analysis within trials indicated that ADF was more precise than ADL. In
      conclusion, in digestibility trials in which fecal output was measured and spot
      samples of the duodenal digesta were obtained, duodenal flow and ruminal
      digestibility of the DM may be estimated from the relationship between the ADF
      concentration in feces and that in the duodenal digesta of ruminants.

PMID- 24440250
TI  - Effect of stocking rate and calving date on dry matter intake, milk production,
      body weight, and body condition score in spring-calving, grass-fed dairy cows.
AB  - The primary objective of the study was to quantify the effect of stocking rate
      (SR) and calving date (CD) on milk production, dry matter intake (DMI), energy
      balance (EB), and milk production efficiency over 4 consecutive years (2009 to
      2012). Two groups of Holstein-Friesian dairy cows with different mean CD were
      established from within the existing research herd at Moorepark (Teagasc,
      Ireland). Animals were assigned to either an early calving (mean CD February 14)
      treatment or a late calving (mean CD March 2) treatment. Animals within each CD
      treatment were randomly allocated to 1 of 3 whole-farm SR treatments: low (LSR;
      2.51 cows/ha), medium (MSR; 2.92 cows/ha), and high (HSR; 3.28 cows/ha), and
      animals remained on the same farmlet for the duration of the study. Individual
      animal DMI was estimated 3 times per year at grass using the n-alkane technique
      in March (spring), May (summer), and September (autumn), corresponding to, on
      average, 45, 132, and 258 d in milk, respectively. A total of 138 spring-calving
      dairy cows were used during each year of the study. The effects of SR, CD,
      season, and their interaction were studied using mixed models. Individual animal
      milk production, body weight, body condition score, and the efficiency of milk
      production were significantly decreased as SR increased due to a reduction in
      herbage availability. The existence of CD * SR * season interactions for
      production, DMI, and EB indicate that delaying the herd mean CD can be an
      effective strategy to minimize the reduction in animal performance, particularly
      in spring at higher SR. This study further confirms the benefits of a new
      approach to the evaluation of herbage allowance known as the individual herbage
      allowance, which encompasses the 3 main factors restricting DMI in rotational
      grazing; namely, the average daily herbage allowance of the group, the intake
      capacity of the individual animal within the group, and the relative intake
      capacity of the animal within the competing herd.

PMID- 24440251
TI  - Invited review: Mid-infrared spectroscopy as phenotyping tool for milk traits.
AB  - Interest in methods that routinely and accurately measure and predict animal
      characteristics is growing in importance, both for quality characterization of
      livestock products and for genetic purposes. Mid-infrared spectroscopy (MIRS) is
      a rapid and cost-effective tool for recording phenotypes at the population level.
      Mid-infrared spectroscopy is based on crossing matter by electromagnetic
      radiation and on the subsequent measure of energy absorption, and it is commonly
      used to determine traditional milk quality traits in official milk laboratories.
      The aim of this review was to focus on the use of MIRS to predict new milk
      phenotypes of economic relevance such as fatty acid and protein composition,
      coagulation properties, acidity, mineral composition, ketone bodies, body energy
      status, and methane emissions. Analysis of the literature demonstrated the
      feasibility of MIRS to predict these traits, with different accuracies and with
      margins of improvement of prediction equations. In general, the reviewed papers
      underlined the influence of data variability, reference method, and unit of
      measurement on the development of robust models. A crucial point in favor of the
      application of MIRS is to stimulate the exchange of data among countries to
      develop equations that take into account the biological variability of the
      studied traits under different conditions. Due to the large variability of
      reference methods used for MIRS calibration, it is essential to standardize the
      methods used within and across countries. 

PMID- 24440253
TI  - Effects of including NaOH-treated corn straw as a substitute for wheat hay in the
      ration of lactating cows on performance, digestibility, and rumen microbial
      profile.
AB  - This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as
      a substitute for 15% wheat hay in the control total mixed ration (TMR) of
      lactating cows on performance, digestibility, and rumen microbial profile. Two
      groups of 21 cows each, similar in initial performance, were fed individually 1
      of the 2 TMR examined. Voluntary dry matter intake of cows fed the control TMR
      was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic
      matter digestibilities of both groups were similar. Crude protein digestibility
      was higher in the control cows but digestibility of neutral detergent fiber
      polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. This
      was followed by 4.6% reduction in rumination time of the T-CS group. A slightly
      higher milk yield was observed in the control cows compared with the T-CS group;
      however, milk fat and milk protein content were higher in cows fed the T-CS TMR.
      This was reflected in 1.3% increase in energy-corrected milk yield and 5.34%
      increase in production efficiency (energy-corrected milk yield/intake) of the T
      CS cows compared with the control. Welfare of the cows, as assessed by length of
      daily recumbence time, was improved by feeding the T-CS TMR relative to the
      control group. As a whole, the rumen bacterial community was significantly
      modulated in the T-CS group in the experimental period compared with the
      preexperimental period, whereas the bacterial community of the control group
      remained unchanged during this period. Out of the 8 bacterial species that were
      quantified using real-time PCR, a notable decrease in cellulolytic bacteria was
      observed in the T-CS group, as well as an increase in lactic acid-utilizing
      bacteria. These results illustrate the effect of T-CS on the composition of rumen
      microbiota, which may play a role in improving the performance of the lactating
      cow. 

PMID- 24440252
TI  - Multiresidue screening of milk withheld for sale at dairy farms in central New
      York State.
AB  - Many of the drugs commonly used in lactating dairy cows result in residues in the
      milk, prohibiting its sale for human consumption. Milk withheld for sale because
      of drug treatment or from cows with high somatic cell counts is commonly called
      "waste milk." One-third of dairy farms in the United States use waste milk to
      feed preweaned dairy calves. Limited information is currently available on the
      effect of this practice on the selection and dissemination of antibiotic
      resistant bacteria. Pooled waste milk samples were collected from 34 dairy farms
      in central New York State with the objective of detecting the presence and
      quantity of drug residues in these samples. Samples were collected and
      refrigerated using ice packs and then stored at 4 degrees C upon arrival at the
      Cornell laboratory (Ithaca, NY). Screening for beta-lactam, tetracycline, and
      sulfonamide residues in the milk was performed using commercial enzyme-linked
      receptor-binding assay (SNAP) tests (Idexx Laboratories Inc., Westbrook, ME).
      Samples with a positive SNAP test were selected for screening using a
      multiresidue liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
      The SNAP tests revealed that 75, 14.3, and 7.1% of waste milk samples (n=34)
      contained beta-lactam, tetracycline, and sulfamethazine residues, respectively.
      Of the samples sent for LC-MS/MS (n=28), half had detectable quantities of drug
      residues. The most prevalent drugs detected by LC-MS/MS were ceftiofur (39.2%;
      mean +/- SE concentration=0.151 +/- 0.042 MUg/mL), penicillin G (14.2%; mean +/-
      SE concentration=0.008 +/- 0.001 ug/mL), and ampicillin (7.1%; mean +/- SE
      concentration=0.472 +/- 0.43 ug/mL). In addition, one sample had detectable
      concentrations of oxytetracycline and one sample had detectable concentrations of
      sulfadimethoxine. These results provide insight on drug residues present in waste
      milk from select farm in upstate New York, and additionally indicate the need for
      additional studies targeting on-farm treatments that could degrade drug residues
      present in waste milk and reduce the potential effects on the biosphere from the
      disposal and use of waste milk as a feed source.

PMID- 24440254
TI  - Selection with inbreeding control in simulated young bull schemes for local dairy
      cattle breeds.
AB  - Local breeds are rarely subject to modern selection techniques; however,
      selection programs will be required if local breeds are to remain a viable
      livelihood option for farmers. Selection in small populations needs to take into
      account accurate inbreeding control. Optimum contribution selection (OCS) is
      efficient in controlling inbreeding and maximizes genetic gain. The current paper
      investigates genetic progress in simulated dairy cattle populations from 500 to
      6,000 cows undergoing young bull selection schemes with OCS compared with
      truncation selection (TS) at an annual inbreeding rate of 0.003. Selection is
      carried out for a dairy trait with a base heritability of 0.3. A young bull
      selection scheme was used because of its simplicity in implementation. With TS,
      annual genetic gain from 0.111 standard deviation units with 500 cows increases
      rapidly to 0.145 standard deviation units with 4,000 cows. Then, genetic gain
      increases more slowly up to 6,000 cows. At the same inbreeding rate, OCS produces
      higher genetic progress than TS. Differences in genetic gain between OCS and TS
      vary from to 2 to 6.3%. Genetic gain is also improved by increasing the number of
      years that males can be used as sires of sires. When comparing OCS versus TS at
      different heritabilities, we observe an advantage of OCS only at high
      heritability, up to 8% with heritability of 0.9. By increasing the constraint on
      inbreeding, the difference of genetic gain between the 2 selection methods
      increases in favor of OCS, and the advantage at the inbreeding rate of 0.001 per
      generation is 6 times more than at the inbreeding rate of 0.003. Opportunities
      exist for selection even in dairy cattle populations of a few hundred females. In
      any case, selection in local breeds will most often require specific investments
      in infrastructure and manpower, including systems for accurate data recording and
      selection skills and the presence of artificial insemination and breeders
      organizations. A cost-benefit analysis is therefore advisable before considering
      the implementation of selection schemes in local dairy cattle breeds. 

PMID- 24440255
TI  - (1)H-Nuclear magnetic resonance-based plasma metabolic profiling of dairy cows
      with clinical and subclinical ketosis.
AB  - The purpose of this study was to assess the metabolic profile of plasma samples
      from cows with clinical and subclinical ketosis. According to clinical signs and
      3-hydroxybutyrate plasma levels, 81 multiparous Holstein cows were selected from
      a dairy farm 7 to 21 d after calving. The cows were divided into 3 groups: cows
      with clinical ketosis, cows with subclinical ketosis, and healthy control cows.
      (1)H-Nuclear magnetic resonance-based metabolomics was used to assess the plasma
      metabolic profiles of the 3 groups. The data were analyzed by principal component
      analysis, partial least squares discriminant analysis, and orthogonal partial
      least-squares discriminant analysis. The differences in metabolites among the 3
      groups were assessed. The orthogonal partial least-squares discriminant analysis
      model differentiated the 3 groups of plasma samples. The model predicted clinical
      ketosis with a sensitivity of 100% and a specificity of 100%. In the case of
      subclinical ketosis, the model had a sensitivity of 97.0% and specificity of
      95.7%. Twenty-five metabolites, including acetoacetate, acetone, lactate,
      glucose, choline, glutamic acid, and glutamine, were different among the 3
      groups. Among the 25 metabolites, 4 were upregulated, 7 were downregulated, and
      14 were both upregulated and downregulated. The results indicated that plasma
      (1)H-nuclear magnetic resonance-based metabolomics, coupled with pattern
      recognition analytical methods, not only has the sensitivity and specificity to
      distinguish cows with clinical and subclinical ketosis from healthy controls, but
      also has the potential to be developed into a clinically useful diagnostic tool
      that could contribute to a further understanding of the disease mechanisms.

PMID- 24440256
TI  - A case study of the carbon footprint of milk from high-performing confinement and
      grass-based dairy farms.
AB  - Life-cycle assessment (LCA) is the preferred methodology to assess carbon
      footprint per unit of milk. The objective of this case study was to apply an LCA
      method to compare carbon footprints of high-performance confinement and grass
      based dairy farms. Physical performance data from research herds were used to
      quantify carbon footprints of a high-performance Irish grass-based dairy system
      and a top-performing United Kingdom (UK) confinement dairy system. For the US
      confinement dairy system, data from the top 5% of herds of a national database
      were used. Life-cycle assessment was applied using the same dairy farm greenhouse
      gas (GHG) model for all dairy systems. The model estimated all on- and off-farm
      GHG sources associated with dairy production until milk is sold from the farm in
      kilograms of carbon dioxide equivalents (CO2-eq) and allocated emissions between
      milk and meat. The carbon footprint of milk was calculated by expressing GHG
      emissions attributed to milk per tonne of energy-corrected milk (ECM). The
      comparison showed that when GHG emissions were only attributed to milk, the
      carbon footprint of milk from the Irish grass-based system (837 kg of CO2-eq/t of
      ECM) was 5% lower than the UK confinement system (884 kg of CO2-eq/t of ECM) and
      7% lower than the US confinement system (898 kg of CO2-eq/t of ECM). However,
      without grassland carbon sequestration, the grass-based and confinement dairy
      systems had similar carbon footprints per tonne of ECM. Emission algorithms and
      allocation of GHG emissions between milk and meat also affected the relative
      difference and order of dairy system carbon footprints. For instance, depending
      on the method chosen to allocate emissions between milk and meat, the relative
      difference between the carbon footprints of grass-based and confinement dairy
      systems varied by 3 to 22%. This indicates that further harmonization of several
      aspects of the LCA methodology is required to compare carbon footprints of
      contrasting dairy systems. In comparison to recent reports that assess the carbon
      footprint of milk from average Irish, UK, and US dairy systems, this case study
      indicates that top-performing herds of the respective nations have carbon
      footprints 27 to 32% lower than average dairy systems. Although differences
      between studies are partly explained by methodological inconsistency, the
      comparison suggests that potential exists to reduce the carbon footprint of milk
      in each of the nations by implementing practices that improve productivity.

PMID- 24440257
TI  - The effect of an exogenous protease on the fermentation and nutritive value of
      high-moisture corn.
AB  - The objective of this study was to determine if treating high-moisture corn at
      harvest with an exogenous protease could accelerate the increase in in vitro
      ruminal starch degradation that is normally found with advancing times of
      ensiling. Ground high-moisture corn (HMC; 73% dry matter) was untreated or
      treated with an exogenous protease to achieve a final concentration of 2,000 mg
      of protease/kg of fresh corn. Corn was ensiled in laboratory-scale bags
      (approximately 500 g) that were evacuated of air, heat-sealed, and stored at 22
      to 23 degrees C for 70 and 140 d. Samples of freshly treated corn samples were
      collected to represent d 0 samples. Treatment of HMC with protease did not affect
      the gross populations of lactic acid bacteria or yeasts throughout the ensiling
      period. Treatment of HMC with protease resulted in higher concentrations of
      lactic acid and ethanol after 70 but not 140 d of ensiling. Concentrations of
      crude protein, water-soluble carbohydrates, and starch were unaffected by
      treatment with protease within each sampling day. After 70 or 140 d of ensiling,
      HMC that was treated with protease had higher concentrations of soluble protein
      (as a % of crude protein) and NH3-N, and had lower concentrations of prolamin
      protein, compared with untreated corn. In vitro rumen degradability (7-h
      incubation) of starch was greater in protease-treated versus untreated corn at
      all sampling days but the difference was more pronounced after 70 and 140 d
      compared with d 0. Concentrations of soluble protein and NH3-N were positively
      correlated with in vitro starch degradation. Conversely, the concentrations of
      prolamin protein in HMC were negatively correlated with in vitro starch
      degradation. Treating HMC with an exogenous protease could be a method to obtain
      greater potential for ruminal starch fermentation after a relatively short period
      of ensiling.

PMID- 24440258
TI  - Segmentation of Parmigiano Reggiano dairies according to cheese-making technology
      and relationships with the aspect of the cheese curd surface at the moment of its
      extraction from the cheese vat.
AB  - Parmigiano Reggiano cheese dairies develop specific cheese-making strategies to
      adapt the variable characteristics of raw, not standardized milk to the final
      goal of obtaining cheese consistent with the standard. Analyzing 1,175 cheese
      making reports from 30 out of 383 dairies associated with the Parmigiano Reggiano
      Consortium in 2010 and 2011, 4 groups of Parmigiano Reggiano dairies using
      specific cheese-making technologies were discriminated by means of multiple
      linear discriminant analysis. Cheese makers manage cheese-making practices to
      obtain curd with different roughness properties, classified according to jargon
      words such as "rigata" and "giusta" or synonyms, because they believe that the
      roughness of the cheese curd surface immediately after the extraction from the
      vat is associated with different whey-draining properties and to the final
      outcome of the cheese. The aspect of the surfaces of the curds produced by the 4
      groups of dairies was different according to the technology applied by each
      group. Cutting of the coagulum when it is still soft for a longer time and faster
      cooking of the cheese curd grains were associated with a less rough appearance of
      the surface of the curd, whereas under the opposite conditions, cutting the
      coagulum when it is firm for a shorter time, led to a curd with a rougher
      surface. These findings partially support the traditional feeling of Parmigiano
      Reggiano cheese makers, who consider the curd surface aspect one of the main
      drivers for their technological choices; to date, however, no data are provided
      about correlation between the aspect of the curd and the quality of the ripened
      cheese. If a sufficiently strong correlation could be demonstrated by the future
      development of the research, the operational effectiveness of Parmigiano Reggiano
      dairies will be able to largely benefit from the availability of sound and early
      process markers. 

PMID- 24440259
TI  - Influence of provision of concentrate at milking on voluntary cow traffic in a
      pasture-based automatic milking system.
AB  - The success of an automatic milking system is generally reliant upon the
      voluntary movement of cows around the farm system and the correct management of
      incentives to achieve a targeted level of cow traffic. The present study
      investigated the effect of providing a small feed reward as an incentive at
      milking on the premilking voluntary waiting time of cows milked on a prototype
      robotic rotary in an Australian pasture-based dairy. The 2 treatments were "feed
      on" (concentrate offered at milking) and "feed off" (no concentrate offered at
      milking), with data from a single herd of 168 lactating dairy cows collected over
      16d. A survival analysis with time-varying covariates was used to model the
      voluntary waiting times of cows in the premilking yard. The median time cows
      spent waiting before milking was 129 min and after 4h just over 70% of the cows
      had exited the yard (volunteered for milking). When feed was provided, cows were
      faster to exit the premilking yard (shorter time spent waiting) and waited just
      over half the time (0.53*) they did during the "feed off" treatment. Heifers
      exited the premilking yard more rapidly than cows in later lactations, with older
      cows spending at least 1.40 times longer in the yard before milking. Average
      daily milk yield along with stage of lactation and fetching cows from the paddock
      also influenced cow traffic in the premilking yard. As the number of cows in the
      premilking yard increased, voluntary waiting time also increased. At a queue
      length of 20 or more cows, the negative effect on waiting time of an additional
      cow entering the yard was less than that when fewer than 20 cows were present.
      Results demonstrated that feeding a small reward on the robotic rotary platform
      can reduce the time cows spend in the premilking yard, leading to a potential
      reduction in the risk of congestion at the dairy, particularly during times of
      high demand. Minimizing congestion will likely benefit multiple aspects of the
      voluntary milking operation, including a potential improvement in robot
      utilization, a reduction in unnecessary time spent off pasture by cows in the
      milking herd, promoting cow welfare through reducing the risk of lameness, and
      enhancing productivity. Targeting strategies to minimize queue length to less
      than the threshold length, which in this study was 20 cows, could result in
      reduced time spent in the premilking yard.

PMID- 24440260
TI  - The effect of feeding canola meal on concentrations of plasma amino acids.
AB  - An initial meta-analysis on isonitrogenous experiments where a protein source was
      replaced by canola meal (CM) showed that CM feeding increased yields of milk and
      milk protein and apparent N efficiency. The objective of the current study was to
      determine if these responses were related to increased changes in plasma AA
      concentrations. Although only half of the experiments of the initial meta
      analysis reported concentrations of plasma AA and could be used in the current
      meta-analysis, lactational responses to CM feeding were similar to those reported
      previously. In the current meta-analysis, CM feeding increased plasma
      concentrations of total AA, total essential AA (EAA) and all individual EAA, but
      decreased concentrations of blood and milk urea-N. The current meta-analysis
      suggests that CM feeding increased the absorption of EAA, which would be
      responsible for the increased milk protein secretion and the increased apparent N
      efficiency. 

PMID- 24440261
TI  - Use of micellar casein concentrate for Greek-style yogurt manufacturing: effects
      on processing and product properties.
AB  - The objective of this work was to develop and optimize an alternative make
      process for Greek-style yogurt (GSY), in which the desired level of protein was
      reached by fortification with micellar casein concentrate (MCC) obtained from
      milk by microfiltration. Two MCC preparations with 58 and 88% total protein (MCC
      58 and MCC-88) were used to fortify yogurt milk to 9.80% (wt/wt) protein.
      Strained GSY of similar protein content was used as the control. Yogurt milk
      bases were inoculated with 0.02% (wt/wt) or 0.04% (wt/wt) direct vat set starter
      culture and fermented until pH 4.5. The acidification rate was faster for the MCC
      fortified GSY than for the control, regardless of the inoculation level, which
      was attributed to the higher nonprotein nitrogen content in the MCC-fortified
      milk. Steady shear rate rheological analysis indicated a shear-thinning behavior
      for all GSY samples, which fitted well with the power law model. Dynamic
      rheological analysis at 5 degrees C showed a weak frequency dependency of the
      elastic modulus (G') and viscous modulus (G") for all GSY samples, with G' > G",
      indicating a weak gel structure. Differences in the magnitude of viscoelastic
      parameters between the 2 types of GSY were found, with G' of MCC-fortified GSY <
      G' of control, indicating a different extent of protein interactionsin the 2
      types of yogurt. Differences were also noticed in water-holding capacity, which
      was lower for the MCC-fortified GSY compared with the control, attributed to
      lower serum protein content in the former. Despite some differences in the
      physicochemical characteristics of the final product compared with GSY
      manufactured by straining, the alternative process developed here is a feasible
      alternative to the traditional GSY make process, with environmental and possibly
      financial benefits to the dairy industry.

PMID- 24440262
TI  - Fall-grown oat to extend the fall grazing season for replacement dairy heifers.
AB  - Our objective was to assess the pasture productivity and forage characteristics
      of 2 fall-grown oat (Avena sativa L.) cultivars, specifically for extending the
      grazing season and reducing reliance on harvested forages by replacement dairy
      heifers. A total of 160 gravid Holstein heifers (80 heifers/yr) were stratified
      by weight, and assigned to 1 of 10 identical research pens (8 heifers/pen).
      Initial body weights were 480 +/- 43.5 kg in 2011 and 509 +/- 39.4 kg in 2012.
      During both years of the trial, four 1.0-ha pasture replicates were seeded in
      August with Ogle oat (Schumitsch Seed Inc., Antigo, WI), and 4 separate, but
      similarly configured, pasture replicates were seeded with Forage Plus oat (Kratz
      Farms, Slinger, WI). Heifer groups were maintained as units, assigned to specific
      pastures, and then allowed to graze fall-oat pastures for 6h daily before
      returning to the barn, where they were offered a forage-based basal total mixed
      ration. Two heifer groups were retained in confinement (without grazing) as
      controls and offered the identical total mixed ration as pasture groups. During
      2011, available forage mass increased with strong linear and quadratic effects
      for both cultivars, peaking at almost 9 Mg/ha on October 31. In contrast, forage
      mass was not affected by evaluation date in 2012, remaining <= 2,639 kg/ha across
      all dates because of droughty climatic conditions. During 2012, Ogle exhibited
      greater forage mass than Forage Plus across all sampling dates (2,678 vs. 1,856
      kg/ha), largely because of its more rapid maturation rate and greater canopy
      height. Estimates of energy density for oat forage ranged from 59.6 to 69.1%
      during 2011, and ranged narrowly from 68.4 to 70.4% during 2012. For 2011,
      responses for both cultivars had strong quadratic character, in which the most
      energy-dense forages occurred in mid November, largely due to accumulation of
      water-soluble carbohydrates that reached maximum concentrations of 18.2 and 15.1%
      for Forage Plus and Ogle, respectively. Across the 2-yr trial, average daily gain
      for grazing heifer groups tended to be greater than heifers remaining in
      confinement (0.85 vs. 0.74 kg/d), but both management strategies produced weight
      gains within reasonable proximity to normal targets for heifers in this weight
      range. Fall-grown oat should be managed as stockpiled forage for deferred
      grazing, and good utilization of fall-oat forage can be accomplished by a one
      time removal of standing forage, facilitated by a single lead wire advanced daily
      to prevent waste.

PMID- 24440263
TI  - Accuracy of direct genomic values for functional traits in Brown Swiss cattle.
AB  - In this study, direct genomic values for the functional traits general
      temperament, milking temperament, aggressiveness, rank order in herd, milking
      speed, udder depth, position of labia, and days to first heat in Brown Swiss
      dairy cattle were estimated based on ~777,000 (777 K) single nucleotide
      polymorphism (SNP) information from 1,126 animals. Accuracy of direct genomic
      values was assessed by a 5-fold cross-validation with 10 replicates. Correlations
      between deregressed proofs and direct genomic values were 0.63 for general
      temperament, 0.73 for milking temperament, 0.69 for aggressiveness, 0.65 for rank
      order in herd, 0.69 for milking speed, 0.71 for udder depth, 0.66 for position of
      labia, and 0.74 for days to first heat. Using the information of ~54,000 (54K)
      SNP led to only marginal deviations in the observed accuracy. Trying to predict
      the 20% youngest bulls led to correlations of 0.55, 0.77, 0.73, 0.55, 0.64, 0.59,
      0.67, and 0.77, respectively, for the traits listed above. Using a novel method
      to estimate the accuracy of a direct genomic value (defined as correlation
      between direct genomic value and true breeding value and accounting for the
      correlation between direct genomic values and conventional breeding values)
      revealed accuracies of 0.37, 0.20, 0.19, 0.27, 0.48, 0.45, 0.36, and 0.12,
      respectively, for the traits listed above. These values are much smaller but
      probably also more realistic than accuracies based on correlations, given the
      heritabilities and samples sizes in this study. Annotation of the largest
      estimated SNP effects revealed 2 candidate genes affecting the traits general
      temperament and days to first heat.

PMID- 24440264
TI  - Characterizing endogenous and exogenous peroxidase activity for bleaching of
      fluid whey and retentate.
AB  - The lactoperoxidase (LP) system may be used to achieve the desired bleaching of
      fluid whey with the addition of low concentrations (<50mg/kg) of hydrogen
      peroxide. The addition of an exogenous peroxidase (EP) to whey may also be used
      to aid in whey bleaching when the LP system is not fully active. The objectives
      of this study were to monitor LP activity in previously refrigerated or frozen
      milk, fluid whey, and whey retentate (10% solids) and to evaluate peroxidase
      activity in fluid whey and whey retentate (10% solids), with and without
      additional EP (2, 1, or 0.5 dairy bleaching units), over a range of pH (5.5-6.5)
      and temperatures (4-60 degrees C). Subsequent experiments were conducted to
      determine the relationship between enzyme activity and bleaching efficacy. Raw
      and pasteurized milk, fat-separated pasteurized whey, and whey retentate (10%
      solids) were evaluated for LP activity following storage at 4 or -20 degrees C,
      using an established colorimetric method. A response surface model was applied to
      evaluate both endogenous and EP activity at various temperatures and pH in
      freshly manufactured whey and retentate. Refrigerated or frozen storage at the
      parameters evaluated did not affect LP activity in milk, whey, or retentate. In
      fluid whey, with and without added EP, as pH decreased (to 5.5) and temperature
      increased (to 60 degrees C), peroxidase activity increased. Retentate with EP
      exhibited behavior similar to that of fluid whey: as pH decreased and temperature
      increased, activity increased. However, in retentate without EP, as pH increased
      and temperature increased, activity increased. Enzyme activity was negatively
      correlated to bleaching time (time for >80% norbixin destruction) in fluid whey
      but a linear relationship was not evident in retentate. When fluid whey is
      bleached enzymatically, if pH is decreased and temperature is increased, the rate
      of reaction increases (e.g., bleaching occurs in less time). When bleaching in
      retentate, a higher pH (pH 6.5 vs. pH 5.5) is desired for optimal bleaching by
      the LP system. Due to processing restraints, this may not be possible for all
      dairy producers to achieve and, thus, addition of EP could be beneficial to
      improve bleaching efficacy. 

PMID- 24440265
TI  - Potential sources of mouth drying in beverages fortified with dairy proteins: A
      comparison of casein- and whey-rich ingredients.
AB  - Oral nutritional supplement drinks (ONS) are beverages high in dairy proteins
      that are prescribed to individuals at risk of malnutrition. Consumption of ONS is
      poor in elderly care facilities, with patients commenting that the sensory
      attributes of these drinks reduce their enjoyment and willingness to consume.
      Mouth drying is an attribute of ONS found to build with repeated consumption,
      which may further limit liking of these products. This study investigated the
      sources of drying sensations by sequential profiling, with a trained sensory
      panel rating a range of model milk systems and ONS over repeated sips and during
      after-effects. Sequential profiling found that fortification of milk with both
      caseinate and whey protein concentrate significantly increased the perception of
      mouth drying over repeated consumption, increasing by between 35 and 85% over
      consumption of 40mL. Enrichment of ONS with either whey protein concentrate or
      milk protein concentrate to a total protein content of 8.7% (wt/wt) resulted in
      whey and casein levels of 4.3:4.4% and 1.7:7.0% respectively. The product higher
      in whey protein was substantially more mouth drying, implying that whey proteins
      may be the most important contributor to mouth drying in ONS. However, efforts to
      mask mouth drying of protein-fortified milk by increasing sweetness or fat level
      were unsuccessful at the levels tested. Increasing the viscosity of protein
      fortified milk led to a small but significant reduction in mouth drying. However,
      this approach was not successful when tested within complete ONS. Further
      analysis is required into the mechanism of protein-derived mouth drying to mask
      negative sensations and improve the enjoyment and consumption of protein-rich
      ONS. 

PMID- 24440266
TI  - Thresholds of whole-blood beta-hydroxybutyrate and glucose concentrations
      measured with an electronic hand-held device to identify ovine hyperketonemia.
AB  - Metabolic disorders, especially hyperketonemia, are very common in dairy sheep.
      The whole-blood concentrations of beta-hydroxybutyrate (BHBA) and glucose can be
      determined by commercially available electronic hand-held devices, which are used
      in human medicine and for the detection of ketosis in dairy cows. The aim of this
      study was to evaluate the suitability of the hand-held device Precision Xceed
      (PX; Abbott Diabetes Care Inc., Abbott Park, IL) to detect hyperketonemia in
      ewes. An additional objective of this study was to evaluate the agreement between
      samples obtained by minimal invasive venipuncture of an ear vein and measurements
      of whole-blood samples from the jugular vein (vena jugularis, v. jug.). Blood
      samples taken from the v. jug. were collected from 358 ewes on 4 different farms.
      These samples and a blood drop obtained from an ear vein were analyzed
      simultaneously on farm with the PX. For method comparison, the samples obtained
      from the v. jug. were also analyzed by standard methods, which served as the gold
      standard at the Central Laboratory of the University of Veterinary Medicine
      Vienna, Austria. The correlation coefficients between the serum BHBA
      concentration and the concentrations measured with the hand-held meter in the
      whole blood from an ear vein and the v. jug. were 0.94 and 0.96, respectively.
      The correlation coefficients of plasma and whole-blood glucose concentration were
      0.68 for the v. jug. and 0.47 for the ear vein. The mean glucose concentration
      was significantly lower in animals classified as hyperketonemic (BHBA >= 1.6
      mmol/L) compared with healthy ewes. Whole-blood concentrations of BHBA and
      glucose measured with the PX from v. jug. showed a constant negative bias of 0.15
      mmol/L and 8.4 mg/dL, respectively. Hence, a receiver operating characteristic
      analysis was performed to determine thresholds for the PX to detect
      hyperketonemia in ewes. This resulted in thresholds for moderate ketosis of BHBA
      concentrations of 0.7 mmol/L in blood from an ear vein and the v. jug. Cutoffs of
      1.0 mmol/L (ear vein) and 1.1 mmol/L (v. jug.) BHBA were determined to detect
      animals at greater risk to develop severe hyperketonemia. Applying these
      thresholds, excellent test characteristics, with sensitivities of 1.00 for both
      samples and specificities of 0.98 for the ear vein and 0.97 for the v. jug. were
      determined. These results demonstrate that the PX is a useful tool for detection
      of hyperketonemia in ewes.

PMID- 24440267
TI  - Effect of high-pressure processing on reduction of Listeria monocytogenes in
      packaged Queso Fresco.
AB  - The effect of high-hydrostatic-pressure processing (HPP) on the survival of a 5
      strain rifampicin-resistant cocktail of Listeria monocytogenes in Queso Fresco
      (QF) was evaluated as a postpackaging intervention. Queso Fresco was made using
      pasteurized, homogenized milk, and was starter-free and not pressed. In phase 1,
      QF slices (12.7 * 7.6 * 1 cm), weighing from 52 to 66 g, were surface inoculated
      with L. monocytogenes (ca. 5.0 log10 cfu/g) and individually double vacuum
      packaged. The slices were then warmed to either 20 or 40 degrees C and HPP
      treated at 200, 400, and 600 MPa for hold times of 5, 10, 15, or 20 min.
      Treatment at 600 MPa was most effective in reducing L. monocytogenes to below the
      detection level of 0.91 log10 cfu/g at all hold times and temperatures. High
      hydrostatic-pressure processing at 40 degrees C, 400 MPa, and hold time >= 15 min
      was effective but resulted in wheying-off and textural changes. In phase 2, L.
      monocytogenes was inoculated either on the slices (ca. 5.0 log10 cfu/g; ON) or in
      the curds (ca. 7.0 log10 cfu/g; IN) before the cheese block was formed and
      sliced. The slices were treated at 20 degrees C and 600 MPa at hold times of 3,
      10, and 20 min, and then stored at 4 and 10 degrees C for 60 d. For both
      treatments, L. monocytogenes became less resistant to pressure as hold time
      increased, with greater percentages of injured cells at 3 and 10 min than at 20
      min, at which the lethality of the process increased. For the IN treatment, with
      hold times of 3 and 10 min, growth of L. monocytogenes increased the first week
      of storage, but was delayed for 1 wk, with a hold time of 20 min. Longer lag
      times in growth of L. monocytogenes during storage at 4 degrees C were observed
      for the ON treatment at hold times of 10 and 20 min, indicating that the IN
      treatment may have provided a more protective environment with less injury to the
      cells than the ON treatment. Similarly, HPP treatment for 10 min followed by
      storage at 4 degrees C was the best method for suppressing the growth of the
      endogenous microflora with bacterial counts remaining below the level of
      detection for 2 out of the 3 QF samples for up to 84 d. Lag times in growth were
      not observed during storage of QF at 10 degrees C. Although HPP reduced L.
      monocytogenes immediately after processing, a second preservation technique is
      necessary to control growth of L. monocytogenes during cold storage. However, the
      results also showed that HPP would be effective for slowing the growth of
      microorganisms that can shorten the shelf life of QF.

PMID- 24440268
TI  - Enterotoxin-producing Staphylococcus aureus genotype B as a major contaminant in
      Swiss raw milk cheese.
AB  - The objective of this study was to characterize Staphylococcus aureus isolates
      from Swiss raw milk cheeses that had been found to be contaminated with coagulase
      positive staphylococci and to estimate the frequency of the various genotypes, in
      particular the mastitis-associated Staph. aureus genotype B (GTB). The isolates
      were also tested for staphylococcal enterotoxin (SE) genes and other virulence
      factors. From 623 coagulase-positive staphylococci isolated from 78 contaminated
      raw milk cheeses, 609 were found to be Staphylococcus aureus. Genotyping of all
      Staph. aureus isolates was performed by PCR amplification of the 16S-23S rRNA
      intergenic spacer region, as this method was used previously to differentiate
      between mastitis subtypes associated with their clinical outcome. In total, 20
      different genotypes were obtained and the 5 most frequently occurring genotypes
      were distributed in 6.4% or more of the samples. The enterotoxin-producing Staph.
      aureus GTB, known for its high contagiousness and increased pathogenicity in
      Swiss mastitis herds, was found to be the most abundant subtype at the sample
      level (71.8%) as well as among the isolates (62.0%). A subset of 107 isolates of
      the different genotypes were analyzed for the presence of SE genes and revealed 9
      different SE gene patterns, with sed being most frequently detected and 26% being
      PCR-negative for SE genes. Almost all isolates of the major contaminant GTB
      contained the SE gene pattern sed, sej, ser, with half of them additionally
      carrying sea. Production of SE in vitro was consistent with the SE genes detected
      in most of the cases; however, some isolated GTB did not produce SEA.
      Staphylococcus aureus Protein A (spa) typing revealed 30 different subtypes and
      most GTB isolates belonged to the bovine spa type t2953; GTB/t2953 was linked
      among other subtypes to SE production in cheese and staphylococcal intoxication
      cases. Furthermore, 1 of the 623 isolates was a methicillin-resistant Staph.
      aureus, which was an seh-carrying Staph. aureus spa type tbl 0635 (non-GTB). We
      conclude that control and reduction of enterotoxigenic Staph. aureus GTB in dairy
      herds in Switzerland will not only prevent economic losses at the farm level but
      also improve the safety of raw milk cheeses; distribution of methicillin
      resistant Staph. aureus via raw milk cheese is of less concern. 

PMID- 24440269
TI  - Status of vitamins E and A and beta-carotene and health in organic dairy cows fed
      a diet without synthetic vitamins.
AB  - Synthetic vitamin supplementation is not consistent with organic production, so
      it is important to investigate whether dairy cows can maintain their health and
      production without synthetic vitamins being added to their diet. In basic dairy
      cow diets, provitamin A (beta-carotene) and vitamin E are mainly found in pasture
      and in grass and legume silages, but the concentrations are highly variable. This
      study compared the vitamin status and health of cows without synthetic vitamin
      supplementation (NSV group) with control cows (CON group) fed synthetic vitamins
      according to Swedish recommendations (600 IU of vitamin E and 80,000 IU of
      vitamin A per cow per day) to investigate whether dairy cows can fulfill their
      requirements of vitamins A and E without supplementation with synthetic vitamins.
      Vitamin concentrations in blood plasma and milk, health, fertility, milk yield,
      and milk composition were measured in Swedish Holstein cows (n=28) during 2
      complete lactations. All cows were fed a 100% organic diet containing grass
      legume silage, cold-pressed rapeseed cake, peas, cereal grains, and minerals.
      Blood samples were collected from each cow 3 wk before expected calving, at
      calving, and 3 wk, 3 to 5 mo, and 7 to 9 mo after calving. Samples of colostrum
      were taken and milk samples were collected 4d after calving and at the same time
      as the 3 blood samplings after calving. The only difference in vitamin status
      between groups was found in colostrum in yr 1, when CON cows tended to have a
      higher concentration of alpha-tocopherol, and their beta-carotene concentration
      was higher compared with NSV cows. The NSV cows tended to have more cases of
      mastitis than CON cows in yr 2. Within the NSV group, fewer cows were healthy and
      more cases of mastitis were observed in yr 2 than in yr 1. The groups did not
      differ in production parameters. In conclusion, the vitamin status in blood and
      milk of the studied cows indicated that cows in organic dairy production can
      fulfill their requirements of vitamins A and E without any supplementation of
      synthetic vitamins, except at the time around calving, when the requirements are
      high. However, the impaired health of NSV cows in yr 2 may indicate a long-term
      negative health effect in cows fed no synthetic vitamins.

PMID- 24440270
TI  - Innovative Caciocavallo cheeses made from a mixture of cow milk with ewe or goat
      milk.
AB  - This study assessed and compared the physicochemical, microbiological, and
      sensorial characteristics of Caciocavallo cheeses, made from cow milk and a
      mixture of cow with ewe or goat milk, during ripening. Different cheese-making
      trials were carried out on an industrial scale following the standard procedure
      of pasta filata cheeses, with some modifications. The percentage of the different
      added milk to cow milk influenced compositional and nutritional characteristics
      of the innovative products, leading to a satisfactory microbiological and
      sensorial quality. 

PMID- 24440271
TI  - Induced lactation in heifers: Effects of dexamethasone and age at induction on
      milk yield and composition.
AB  - Milk production in heifers induced into lactation is lower than that of
      postpartum primiparous cows. A method to improve milk production in induced
      lactations may provide opportunities for increased profitability as well as
      increase our understanding of the mechanisms that regulate mammary gland
      development and colostrum composition. The present study was conducted to
      determine if dexamethasone administration at the onset of milking or age at
      lactation induction would affect milk production in heifers induced into
      lactation. Holstein heifers at 14 [n=20; 354 +/- 38 kg of body weight (BW)] and
      18 mo of age (n=20; 456 +/- 30 kg of BW) were assigned randomly to dexamethasone
      (DEX) or control (CON) treatment groups in a 2 * 2 factorial arrangement with age
      and dexamethasone treatment as the 2 factors. Heifers were induced into lactation
      with daily subcutaneous injections of estradiol-17beta and progesterone (0.075
      and 0.25 mg/kg of BW per d, respectively) on experimental d 1 to 7. They also
      received bovine somatotropin (bST) every 14 d beginning on experimental d 1.
      Milking began on experiment d 18 (lactation d 1). Dexamethasone (10mg) was
      administered on lactation d 1 and 2 following the morning milking; CON heifers
      did not receive dexamethasone. Milk yield from d2 to 15 of lactation of heifers
      receiving DEX (7.8 kg/d) was greater than that of CON heifers (6.0 kg/d) but was
      similar thereafter through 305 d of lactation (18.2 kg/d). Milk production to d
      11 was similar for 14- and 18-mo-old heifers but was greater for 18- (18.9 kg/d)
      than for 14-mo-old animals (17.4 kg/d) through 305 d in milk. Milk fat percentage
      increased initially and was greater in DEX (4.51%) compared with CON (3.53%)
      heifers until 21 d in milk. Milk protein and lactose concentrations were not
      affected by DEX treatment. Age at induction did not affect milk fat, protein, or
      lactose percentages. Mean milk IgG concentration declined from 107.4 mg/mL on d 1
      to 5.0mg/mL on d 7 of lactation, tended to be greater for 18- compared with 14-mo
      old heifers, and was not different due to DEX treatment. Administration of DEX to
      heifers induced into lactation increased initial milk production during the first
      2 wk of lactation but this effect did not persist through 305 DIM. Treatment with
      DEX appeared to stimulate mammary cell differentiation but did not change the
      rate of decline of milk IgG concentrations. Higher milk yield in 18-mo-old
      heifers may be due to greater mammary epithelium, higher body mass, or both.

PMID- 24440272
TI  - Investigating the feasibility of scale up and automation of human induced
      pluripotent stem cells cultured in aggregates in feeder free conditions.
AB  - The transfer of a laboratory process into a manufacturing facility is one of the
      most critical steps required for the large scale production of cell-based therapy
      products. This study describes the first published protocol for scalable
      automated expansion of human induced pluripotent stem cell lines growing in
      aggregates in feeder-free and chemically defined medium. Cells were successfully
      transferred between different sites representative of research and manufacturing
      settings; and passaged manually and using the CompacT SelecT automation platform.
      Modified protocols were developed for the automated system and the management of
      cells aggregates (clumps) was identified as the critical step. Cellular
      morphology, pluripotency gene expression and differentiation into the three germ
      layers have been used compare the outcomes of manual and automated processes. 

PMID- 24440274
TI  - Remember empathy.

PMID- 24440275
TI  - The role of MAPK signalling pathways in the response to endoplasmic reticulum
      stress.
AB  - Perturbations in endoplasmic reticulum (ER) homeostasis, including depletion of
      Ca(2+) or altered redox status, induce ER stress due to protein accumulation,
      misfolding and oxidation. This activates the unfolded protein response (UPR) to
      re-establish the balance between ER protein folding capacity and protein load,
      resulting in cell survival or, following chronic ER stress, promotes cell death.
      The mechanisms for the transition between adaptation to ER stress and ER stress
      induced cell death are still being understood. However, the identification of
      numerous points of cross-talk between the UPR and mitogen-activated protein
      kinase (MAPK) signalling pathways may contribute to our understanding of the
      consequences of ER stress. Indeed, the MAPK signalling network is known to
      regulate cell cycle progression and cell survival or death responses following a
      variety of stresses. In this article, we review UPR signalling and the activation
      of MAPK signalling pathways in response to ER stress. In addition, we highlight
      components of the UPR that are modulated in response to MAPK signalling and the
      consequences of this cross-talk. We also describe several diseases, including
      cancer, type II diabetes and retinal degeneration, where activation of the UPR
      and MAPK signalling contribute to disease progression and highlight potential
      avenues for therapeutic intervention. This article is part of a Special Issue
      entitled: Calcium Signaling In Health and Disease. Guest Editors: Geert Bultynck,
      Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. 

PMID- 24440276
TI  - Endoplasmic reticulum stress associated responses in cancer.
AB  - The endoplasmic reticulum (ER) is responsible for many housekeeping functions
      within the cell and is an important site for pathways that regulates its state of
      homeostasis. When cellular states perturb ER functions, a phenomenon termed "ER
      stress" activates a number of pathways to counteract the associated damages;
      these pathways are together called the unfolded protein response (UPR). The UPR
      has a dualistic function; it exists to alleviate damage associated with ER
      stress, however, if this is not possible, then it signals for cell death through
      apoptosis. Cancer cells are shown to be very resilient under extreme
      environmental stress and an increasing number of studies have indicated that this
      may be largely due to an altered state of the UPR. The role of ER stress and the
      UPR in cancer is still not clear, however many components are involved and may
      prove to be promising targets in future anti-cancer therapy. This article is part
      of a Special Issue entitled: Calcium Signaling in Health and Disease. Guest
      Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and
      Marc Moreau.

PMID- 24440273
TI  - DSM-5 latent classes of alcohol users in a population-based sample: results from
      the Sao Paulo Megacity Mental Health Survey, Brazil.
AB  - BACKGROUND: We aimed to identify different categorical phenotypes based upon the
      DSM-V criteria of alcohol use disorders (AUD) among alcohol users who had at
      least one drink per week in the past year (n=948). METHODS: Data are from the Sao
      Paulo Megacity Mental Health Survey collected in 2005-2007, as part of the World
      Mental Health Survey Initiative. A latent class analysis of the 11 DSM-5-AUD
      criteria was performed using Mplus, taking into account complex survey design
      features. Weighted logistic regression models were used to examine demographic
      correlates of the DSM-5-AUD latent classes. RESULTS: The best latent-class model
      was a three-class model. We found a "non-symptomatic class" (69.7%), a "use in
      larger amounts class" (23.2%), defined by high probability (>70%) of the "use in
      larger amounts" criterion only, and a "high-moderate symptomatic class" (7.1%),
      defined by high-moderate probability of all the 11 AUD criteria. Compared to
      those in the non-symptomatic class, individuals in the "high-moderate symptomatic
      class" were more likely to have been married, have lower educational attainment
      and to be unemployed or in non-regular/informal employment. Those on the "use in
      larger amounts class" were more likely to have been married or never married.
      CONCLUSION: The two symptomatic classes clearly represented the dimensionality of
      the new proposed AUD criteria, and could be more specifically targeted by
      different prevention or treatment strategies. DSM-5-AUD has the advantage of
      shedding light on risky drinkers included in the "use in larger amounts class",
      allowing for preventive interventions, which will reach a large number of
      individuals.

PMID- 24440277
TI  - Specific aquaporins facilitate Nox-produced hydrogen peroxide transport through
      plasma membrane in leukaemia cells.
AB  - In the last decade, the generation and the role of reactive oxygen species (ROS),
      particularly hydrogen peroxide, in cell signalling transduction pathways have
      been intensively studied, and it is now clear that an increase of ROS level
      affects cellular growth and proliferation pathways related to cancer development.
      Hydrogen peroxide (H2O2) has been long thought to permeate biological membranes
      by simple diffusion since recent evidence challenged this notion disclosing the
      role of aquaporin water channels (AQP) in mediating H2O2 transport across plasma
      membranes. We previously demonstrated that NAD(P)H oxidase (Nox)-generated ROS
      sustain glucose uptake and cellular proliferation in leukaemia cells. The aim of
      this study was to assess whether specific AQP isoforms can channel Nox-produced
      H2O2 across the plasma membrane of leukaemia cells affecting downstream pathways
      linked to cell proliferation. In this work, we demonstrate that AQP inhibition
      caused a decrease in intracellular ROS accumulation in leukaemia cells both when
      H2O2 was produced by Nox enzymes and when it was exogenously added. Furthermore,
      AQP8 overexpression or silencing resulted to modulate VEGF capacity of triggering
      an H2O2 intracellular level increase or decrease, respectively. Finally, we
      report that AQP8 is capable of increasing H2O2-induced phosphorylation of both
      PI3K and p38 MAPK and that AQP8 expression affected positively cell
      proliferation. Taken together, the results here reported indicate that AQP8 is
      able to modulate H2O2 transport through the plasma membrane affecting redox
      signalling linked to leukaemia cell proliferation. 

PMID- 24440278
TI  - How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing
      pleuritis from epithelioid and sarcomatoid mesotheliomas? An international
      collaborative study.
AB  - OBJECTIVE: Mesothelial hyperplasia (MH) and fibrosing pleuritis (FP) can be
      difficult to distinguish from epithelioid (MM-E) and sarcomatoid (MM-S) malignant
      pleural mesotheliomas. GLUT-1 has shown variable results regarding its
      sensitivity and specificity when used to evaluate mesothelial proliferations. We
      evaluated the utility of GLUT-1 immunostaining in differentiating MH and FP from
      MM-E and MM-S. MATERIALS AND METHODS: In this retrospective study, diagnostically
      well-characterized cases (MH=31, FP=29, MM-E=41, MM-S=29) were collected and
      manually stained for GLUT-1. All slides were visually scored by 2 pathologists;
      using the following system: 0%, 1+ 1-25%, 2+ 26-50% and 3+ >51% cells staining.
      RESULTS: All benign cases (n=60) were negative for GLUT-1 while 45 of 78 (58%) MM
      [21 of 41 (50%) MM-E, 21 of 29 (72%) MM-S and 3 of 3 biphasic mesothelioma
      (100%)] had 1+ to 3+ staining. Of the MM-E, 10 had 1+, and 11 had 2+ staining; of
      the MM-S 3 had 1+, 15 had 2+ and 3 had 3+ staining. Both sarcomatoid and
      epithelioid components of the 3 biphasic mesotheliomas revealed 1+ staining. All
      5 desmoplastic MM were negative. CONCLUSIONS: Positive staining with GLUT-1 is
      helpful since it is present in half of MM-E and three-quarter of MM-S. Although
      all reactive mesothelial lesions were negative, the absence of immunoreactivity
      does not exclude the diagnosis of MM. As with all IHC stains used for diagnostic
      purposes, GLUT-1 has to be a part of a panel, and the results interpreted in the
      context of clinical, radiological and histological findings.

PMID- 24440280
TI  - Acquired perforating dermatosis: a report of 8 cases.
AB  - Acquired perforating dermatosis (APD) is an uncommon disease characterized by
      lesions exhibiting transepidermal elimination of collagen or elastic fibers. APD
      affects adults and is associated with systemic diseases, mainly diabetes mellitus
      and renal failure. We present 8 cases of APD. Seven patients had concomitant
      diabetes mellitus with or without chronic renal failure, and 1 had alcoholic
      cirrhosis. In the patients with chronic renal failure, the onset of APD coincided
      with transient worsening of renal function. The mean increase in creatinine
      concentrations above baseline was 1.14mg/dL. Acute deterioration of renal
      function may be involved in APD. Further studies are needed to investigate this
      association.

PMID- 24440279
TI  - A multicenter phase II study of sorafenib monotherapy in clinically selected
      patients with advanced lung adenocarcinoma after failure of EGFR-TKI therapy
      (Chinese Thoracic Oncology Group, CTONG 0805).
AB  - OBJECTIVES: Aim of the study was to investigate efficacy and safety of sorafenib
      in patients with advanced lung adenocarcinoma after failure of epidermal growth
      factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy. PATIENTS AND
      METHODS: Patients who were diagnosed with stage IIIB or stage IV lung
      adenocarcinoma, and benefited from one prior EGFR-TKI therapy and then failed,
      were eligible. No more than one previous chemotherapy regimen was permitted.
      Patients received oral sorafenib 400mg twice daily continuously until disease
      progression or intolerable toxicity. Primary endpoint was disease control rate
      (DCR). Secondary endpoints included safety, progression-free survival (PFS) and
      overall survival (OS). For patients who agreed to provide peripheral blood or
      tumor tissue, we analyzed the genotype of Bcl-2-interacting mediator of cell
      death (BIM) deletion polymorphism and EGFR mutation status. RESULTS: Of 65
      enrolled patients, 64 were evaluable. The DCR was 32.8%, which did not meet the
      predefined statistical hypothesis of 38.4%. The median PFS and OS were 3.7 months
      [95% (confidence interval), 3.5-3.9 months] and 7.4 months (95% CI, 5.7-9.2
      months), respectively. Logistic regression analysis showed no correlation between
      DCR and age, gender, smoking status and performance status. Hand-foot syndrome
      (HFS) was the predominant toxicity occurring in 71.9% of patients. Fourteen
      patients (21.9%) had >= grade 2 dermatologic reactions that resulted sorafenib
      dose reduction in three patients (4.7%). Of 36 patients, the BIM deletion
      polymorphism was found in 3, and no response to sorafenib was observed. In 30
      tumor tissues, 22 EGFR active mutations were found. The DCR had no significant
      difference between mutation-positive and wild-type patients (31.8% vs. 42.9%,
      respectively; HR, 0.622; p=0.665). CONCLUSION: Sorafenib monotherapy did not
      achieve positive result in patients defined in our trial and we need better
      biomarker to determine the population who can benefit from sorafenib treatment
      (ClinicalTrials.gov number: NCT00922584).

PMID- 24440281
TI  - Cutaneous infection with Alternaria triticina in a Bilateral lung transplant
      recipient.
AB  - We report the case of a 60-year-old man who was receiving immunosuppressive
      therapy for a bilateral lung transplant and presented with a crusted, violaceous
      plaque on the left hand. Based on histopathology and microbiological culture the
      patient was diagnosed with infection by Alternaria species. Treatment with
      itraconazole led to complete resolution of the skin lesion. Forty months later he
      developed four reddish, nodular, skin lesions on the left leg. Analysis of a
      biopsy from one of these lesions using histopathologic and molecular techniques
      identified a mold that shared 98% homology with a strain of Alternaria triticina.
      Alternaria species belong to a group of dematiaceous fungi that cause
      opportunistic infections in humans. The incidence of these infections is
      increasing, mainly in transplant centers. To the best of our knowledge, this is
      the first reported case of a human infection caused by A. triticina. 

PMID- 24440282
TI  - Mate pair sequencing of oropharyngeal squamous cell carcinomas reveals that HPV
      integration occurs much less frequently than in cervical cancer.
AB  - BACKGROUND: Human papillomavirus (HPV) is now recognized to be very important in
      the pathogenesis of oropharyngeal squamous cell carcinoma (OPSCC). It is not
      clear yet whether the physical status of HPV in OPSCC is similar to what is found
      in cervical cancer. STUDY DESIGN: We performed genome-wide mate pair next
      generation sequencing from 20 OPSCCs patients, thirteen of which were positive
      for HPV16 to determine the HPV physical status and its relationship to HPV
      oncogene E6 and E7 expression. RESULTS: This high throughput approach detected
      HPV integration events and also determined the bridged HPV coverage in each
      sample. Two of the HPV16-positive OPSCCs had HPV integration and one of the HPV16
      negative OPSCCs had an HPV26 integration. We mapped the site of integration in
      the HPV genome in all integration events and the integrations were located at E1,
      E5, E6 and L2 region respectively. One HPV positive OPSCC had two integration
      events but also had a very high bridged HPV coverage, while the other two just
      had HPV integrated into the human genome. CONCLUSION: Our results are thus
      different from what is routinely observed in cervical cancer where HPV is almost
      always integrated into the human genome with loss of episomal HPV sequences. Thus
      more investigation should be carried out to study how episomal HPV alone can
      contribute to the development of most OPSCCs.

PMID- 24440283
TI  - Component resolution reveals additional major allergens in patients with honeybee
      venom allergy.
AB  - BACKGROUND: Detection of IgE to recombinant Hymenoptera venom allergens has been
      suggested to improve the diagnostic precision in Hymenoptera venom allergy.
      However, the frequency of sensitization to the only available recombinant
      honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited,
      suggesting that additional HBV allergens might be of relevance. OBJECTIVE: We
      performed an analysis of sensitization profiles of patients with HBV allergy to a
      panel of HBV allergens. METHODS: Diagnosis of HBV allergy (n = 144) was based on
      history, skin test results, and allergen-specific IgE levels to HBV. IgE
      reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants
      (CCD) was analyzed by ImmunoCAP. RESULTS: IgE reactivity to rApi m 1, rApi m 2,
      rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%,
      22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive
      results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api
      m 3, Api m 10, or both was detected in 68.0% and represented the only HBV
      allergen-specific IgE in 5% of the patients. Limited inhibition of IgE binding by
      therapeutic HBV and limited induction of Api m 3- and Api m 10-specific IgG4 in
      patients obtaining immunotherapy supports recent reports on the
      underrepresentation of these allergens in therapeutic HBV preparations.
      CONCLUSION: Analysis of a panel of CCD-free HBV allergens improved diagnostic
      sensitivity compared with use of rApi m 1 alone, identified additional major
      allergens, and revealed sensitizations to allergens that have been reported to be
      absent or underrepresented in therapeutic HBV preparations.

PMID- 24440284
TI  - Diagnosis and classification of Vogt-Koyanagi-Harada disease.
AB  - Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder that affects
      pigmented tissues of the body, with its most dire manifestations affecting the
      eyes. This review focuses on the diagnostic criteria of VKH disease, including
      some information on history, epidemiology, appropriate clinical and
      classification criteria, etiopathogenesis, treatment and outcomes. Expert review
      of most relevant literature from the disease's first description to 2013 and
      correlation with the experience in the care of VKH disease patients at a tertiary
      Uveitis Service in Brazil gathered over the past 40 years. The clinical
      manifestations and ancillary assessment of VKH disease have been summarized in
      the Revised Diagnostic Criteria proposed in 2001 in a manner that allows
      systematic diagnosis of both acute and chronic patients. It includes the early
      acute uveitic manifestations (bilateral diffuse choroiditis with bullous serous
      retinal detachment and optic disk hyperemia), the late ocular manifestations
      (diffuse fundus depigmentation, nummular depigmented scars, retinal pigment
      epithelium clumping and/or migration, recurrent or chronic anterior uveitis),
      besides the extraocular manifestations (neurological/auditory and integumentary).
      There are two exclusion criteria, i.e. absence of previous ocular penetrating
      trauma or surgery and any other ocular disease that could be confounded with VKH
      disease. HLA-DRB1*0405 plays an important role in pathogenesis, rendering
      carriers more susceptible to disease. The primary ocular pathological feature is
      a diffuse thickening of the uveal tract in the acute phase. Later on, there may
      be a compromise of choriocapillaris, retinal pigment epithelium and outer retina,
      mostly due to an "upstream" effect, with clinical correlates as fundus
      derangements. Functional tests (electroretinogram and visual field testing) as
      well as imaging modalities (retinography, fluorescein/indocyanine green
      angiography, optical coherence tomography and ultrasound) play an important role
      in diagnosis, severity grading as well as disease monitorization. Though high
      dose systemic corticosteroids remain gold-standard therapy, refractory cases may
      need other agents (cyclosporine A, anti-metabolites and biological agents). In
      spite of good visual outcomes in the majority of patients, knowledge about
      disease progression even after the acute phase and its impact on visual function
      warrant further investigation.

PMID- 24440285
TI  - Putting the value into biosimilar decision making: the judgment value criteria.
AB  - Uncertainties remain the key issue surrounding biosimilars, although decisions
      regarding their use must be made. The challenges for policymakers, doctors,
      patients and others seeking to navigate in the uncharted waters of biosimilars
      must be clarified. At the most basic level, scientific understanding of the issue
      remains limited and when making decisions, policymakers must consider all those
      affected by health policy decisions, particularly the ultimate recipients of
      these medicines: the patients. The biosimilar-value chain relies on measurement
      of comparabilities. The goal is to demonstrate how, from a molecular perspective,
      closely similar they are or are not and how potential small differences may be
      relevant to clinical outcomes. To critically understand these points, this
      conceptual paper will present a knowledge-value chain and discuss each dimension
      assigning value in the decision making process re-utilization of biosimilars. 

PMID- 24440286
TI  - Thymoma-associated myasthenia gravis: On the search for a pathogen signature.
AB  - Myasthenia gravis (MG) is an autoimmune disease mainly mediated by anti
      acetylcholine receptor (AChR) antibodies. In the late onset, a thymoma, tumor of
      the thymus, is quite frequent. However, the events leading to thymoma and MG are
      not understood. As thymoma-associated MG (MG-T) patients also display anti
      interferon type I (IFN-I) neutralizing antibodies, we investigated if MG-T could
      be associated with an anti-viral signature. RT-PCR analyses demonstrated huge
      increases of IFN-I subtypes, IFN-alpha2, -alpha8, -omega and -beta, in thymoma
      associated MG but not in thymomas without MG or in control thymuses. Next, we
      investigated if dsRNA signaling pathway involvement could be observed in MG-T, as
      recently observed in early-onset MG. We observed an abnormal regulation of dsRNA
      sensing molecules with an increase of toll-like receptor 3 (TLR3), and a decrease
      of protein kinase R (PKR) and dsRNA helicases (RIG-I and MDA5) in thymoma from MG
      patients. We also detected a decreased expression of p53, the tumor suppressor
      that is known to be down-regulated by dsRNA. Altogether, these results strongly
      suggest that MG-T could be linked to a viral infection. As p16 (CDKN2A), a marker
      of HPV infections, was up-regulated in MG-T, we thus screened DNA from thymomas
      for human papillomavirus (HPV) by real-time PCR using HPV consensus SPF10
      primers. RT-PCR results were negative for all samples tested. We confirmed the
      absence of HPV DNA detection by end point PCR using FAP primers to amplify a
      larger panel of HPV genotypes. Our data clearly demonstrate INF-I overexpression
      together with the activation of innate immunity pathways in thymoma-associated MG
      suggesting that MG might develop after a pathogen infection. We were not able to
      relate thymoma to HPV infections and the implication of other pathogens is
      discussed. 

PMID- 24440287
TI  - Association between complement factor H Val62Ile polymorphism and age-related
      macular degeneration susceptibility: a meta-analysis.
AB  - BACKGROUND: An increasing body of studies has assessed the contribution of
      Val62Ile polymorphism to age-related macular degeneration (AMD) risk, but the
      exact association still remains uncertain. This meta-analysis was undertaken in
      order to further characterize the potential association between Val62Ile
      polymorphism and AMD risk in four different ethnic populations. METHODS: A meta
      analysis was performed using data available from 16 case-control studies
      evaluating correlation between the Val62Ile polymorphism and AMD in Caucasian,
      Chinese, Japanese and South Korean populations. Data extraction and study quality
      assessment were performed in duplicate. Summary odds ratios (ORs) and 95%
      confidence intervals (CIs) of allele contrast and genotype contrast were
      estimated using the random-effects model. The Q-statistic test was used to
      identify heterogeneity, and the funnel plot was adopted to evaluate publication
      bias. RESULTS: Sixteen studies involving a total of 11,400 subjects based on the
      search criteria were included in the meta-analysis. In overall populations, the
      Val62Ile polymorphism seemed to be associated with AMD (ORAA vs. GG=0.40, 95%
      CI=0.28-0.59; ORAA+GA vs. GG=0.72, 95% CI=0.64-0.80; ORAA vs. GC+GG=0.50, 95%
      CI=0.36-0.70; ORA vs. G=0.68, 95% CI=0.58-0.78; ORGA vs. GG=0.71, 95% CI=0.65
      0.77). Similarly, subgroup analysis also revealed that this polymorphism was
      related to AMD in all ethnicities. CONCLUSIONS: This meta-analysis suggested that
      Val62Ile polymorphism was associated with susceptibility to AMD.

PMID- 24440288
TI  - Mitochondrial DNA profiling via genomic analysis in mesial temporal lobe epilepsy
      patients with hippocampal sclerosis.
AB  - INTRODUCTION: Mitochondria have an essential role in neuronal excitability and
      neuronal survival. In addition to energy production, mitochondria also play a
      crucial role in the maintenance of intracellular calcium homeostasis, generation
      of reactive oxygen species and mechanisms of cell death. There is a relative
      paucity of data about the role of mitochondria in epilepsy. Mitochondrial genome
      analysis is rarely carried out in the investigation of some diseases. In mesial
      temporal lobe epilepsies (MTLE) cases, genome analysis has never been used
      previously. The aim of this study is to show mitochondrial dysfunctions using
      genome analysis in patients with MTLE-hippocampal sclerosis (HS). METHODS: 44
      patients with MTLE-HS and 86 matched healthy unrelated controls were included in
      this study. The patients were divided into four groups according to their
      clinical presentation as the following: Group 1 consists of patients with
      intractable epilepsy who refused operation; Group 2 of operated seizure free
      patients; Group 3 of operated patients with seizures; and Group 4 unoperated
      seizure free patients with or without antiepileptic drugs. Blood samples were
      used to isolate DNA. Parallel tagged sequencing was employed to allow
      pyrosequencing of 130 samples. Complete mtDNA is amplified in two overlapping
      fragments (11 and 9 kb). The PCR amplicons were pooled in equimolar ratios.
      Titanium kits were used to produce shotgun libraries according to the
      manufacturer's protocol. RESULTS: The average coverage in total was 130 +/- 30
      and an average of 2365127 bases and 337 bp fragment length was received from all
      samples. The mean mtDNA heteroplasmy in patients was 26.35 +/- 12.3 and in
      controls 25.03 +/- 9.34. Three mutations had prominently high significance in
      patient samples. The most significantly associated variation was located in the
      MT-ATP-8 gene (8502 A>T, Asn46Ile) whereas the other two were in the MT-ND4
      (11994 C>T, Thr412Ile) and MT-ND5 (13231 A>C, Lys299Gln) genes. CONCLUSIONS: We
      have observed that three mutations were significantly related to the presence of
      epilepsy. These mutations were found at the 8502, 11994, and 13,231 bp of mtDNA,
      which resulted in amino acid changes at the MT-ATP-8, MT-ND4 and MT-ND5 genes.
      Finding mutations can lead us to knowing more about the pathophysiology of the
      MTLE disease.

PMID- 24440289
TI  - Single primer amplification reaction (SPAR) methods reveal subsequent increase in
      genetic variations in micropropagated plants of Nepenthes khasiana Hook. f.
      maintained for three consecutive regenerations.
AB  - The genetic fidelity of in vitro-raised plants of three successive regenerations
      of Nepenthes khasiana Hook. f. was assessed using three different single primer
      amplification reaction (SPAR) methods, viz., random amplified polymorphic DNA
      (RAPD), inter-simple sequence repeat (ISSR) and direct amplification of
      minisatellite DNA region (DAMD) markers. Out of 80 RAPD primers screened, 14
      primers reflected a genetic variation of 4.1% in the first regeneration which was
      increased to 9.4% in the third regeneration. In the case of ISSR, out of 36
      primers screened for assessment of genetic homogeneity of the regenerated
      plantlets, 12 primers showed an increase of genetic variation from 4.3% to 10%
      from the first to the third regenerations. In DAMD profiling, 15 primers were
      used for the evaluation of genetic fidelity where 8.47% of polymorphism was
      observed in the first regeneration which was increased to 13.33% in the third
      regeneration. The cumulative analysis reflected a genetic variation of 5.65% in
      the first regeneration which increased subsequently to 7.77% in the second
      regeneration and 10.87% in the third regeneration. The present study demonstrates
      SPAR technique to be an efficient tool for the assessment of clonal fidelity of
      in vitro-raised plants.

PMID- 24440290
TI  - Altered gene dosage confirms the genetic interaction between FIAT and alphaNAC.
AB  - Factor inhibiting ATF4-mediated transcription (FIAT) interacts with Nascent
      polypeptide associated complex and coregulator alpha (alphaNAC). In cultured
      osteoblastic cells, this interaction contributes to maximal FIAT-mediated
      inhibition of Osteocalcin (Ocn) gene transcription. We set out to demonstrate the
      physiological relevance of this interaction by altering gene dosage in compound
      Fiat and Naca (encoding alphaNAC) heterozygous mice. Compound Naca(+/-); Fiat(+/
      ) heterozygous animals were viable, developed normally, and exhibited no
      significant difference in body weight compared with control littermate genotypes.
      Animals with a single Fiat allele had reduced Fiat mRNA expression without
      changes in the expression of related family members. Expression of the osteocyte
      differentiation marker Dmp1 was elevated in compound heterozygotes. Static
      histomorphometry parameters were assessed at 8weeks of age using microcomputed
      tomography (MUCT). Trabecular measurements were not different between genotypes.
      Cortical thickness and area were not affected by gene dosage, but we measured a
      significant increase in cortical porosity in compound heterozygous mice, without
      changes in biomechanical parameters. The bone phenotype of compound Naca(+/-);
      Fiat(+/-) heterozygotes confirms that FIAT and alphaNAC are part of a common
      genetic pathway and support a role for the FIAT/alphaNAC interaction in normal
      bone physiology. 

PMID- 24440291
TI  - Characterization of three Arabidopsis thaliana immunophilin genes involved in the
      plant defense response against Pseudomonas syringae.
AB  - Plant immunophilins are a broadly conserved family of proteins, which carry out a
      variety of cellular functions. In this study, we investigated three immunophilin
      genes involved in the Arabidopsis thaliana response to Pseudomonas syringae
      infection: a cytoplasmic localized AtCYP19, a cytoplasmic and nuclear localized
      AtCYP57, and one nucleus directed FKBP known as AtFKBP65. Arabidopsis knock-out
      mutations in these immunophilins result in an increased susceptibility to P.
      syringae, whereas overexpression of these genes alters the transcription profile
      of pathogen-related defense genes and led to enhanced resistance. Histochemical
      analysis revealed local gene expression of AtCYP19, AtCYP57, and AtFKBP65 in
      response to pathogen infection. AtCYP19 was shown to be involved in reactive
      oxygen species production, and both AtCYP57 and AtFKBP65 provided callose
      accumulation in plant cell wall. Identification of the involvement of these genes
      in biotic stress response brings a new set of data that will advance plant immune
      system research and can be widely used for further investigation in this area.

PMID- 24440292
TI  - A complex microcephaly syndrome in a Pakistani family associated with a novel
      missense mutation in RBBP8 and a heterozygous deletion in NRXN1.
AB  - We report on a consanguineous Pakistani family with a severe congenital
      microcephaly syndrome resembling the Seckel syndrome and Jawad syndrome. The
      affected individuals in this family were born to consanguineous parents of whom
      the mother presented with mild intellectual disability (ID), epilepsy and
      diabetes mellitus. The two living affected brothers presented with microcephaly,
      white matter disease of the brain, hyponychia, dysmorphic facial features with
      synophrys, epilepsy, diabetes mellitus and ID. Genotyping with a 250K SNP array
      in both affected brothers revealed an 18 MB homozygous region on chromosome 18
      p11.21-q12.1 encompassing the SCKL2 locus of the Seckel and Jawad syndromes.
      Sequencing of the RBBP8 gene, underlying the Seckel and Jawad syndromes,
      identified the novel mutation c.919A>G, p.Arg307Gly, segregating in a recessive
      manner in the family. In addition, in the two affected brothers and their mother
      we have also found a heterozygous 607kb deletion, encompassing exons 13-19 of
      NRXN1. Bidirectional sequencing of the coding exons of NRXN1 did not reveal any
      other mutation on the other allele. It thus appears that the phenotype of the
      mildly affected mother can be explained by the NRXN1 deletion, whereas the more
      severe and complex microcephalic phenotype of the two affected brothers is due to
      the simultaneous deletion in NRXN1 and the homozygous missense mutation affecting
      RBBP8.

PMID- 24440293
TI  - Differential gene expression identified by RNA-Seq and qPCR in two sizes of pearl
      oyster (Pinctada fucata).
AB  - Differential growth of the pearl oyster Pinctada fucata still exists in the
      aquaculture production. There is no systematic study of the entire transcriptome
      of differential gene expression in P. fucata in the literature. In this study,
      high-throughput Illumina/HiSeqTM 2000 RNA-Seq was used to examine the differences
      of gene expression in large (L) and small oysters (S). In total, 74,293 and
      76,635 unigenes were generated from L and S oysters, respectively. RT
      quantitative PCR (qPCR) analysis showed that the differential expression pattern
      of 19 out of 34 selected genes was consistent with the results of RNA-Seq
      analysis: 14 genes (11 for growth, 1 for reproduction and 2 for shell formation)
      were expressed more highly in S, 5 genes (1 for growth, 1 for reproduction and 3
      for the immune system) were expressed more highly in L; 3 genes associated with
      the immune system were opposite to it; and no difference was found for the
      remaining 12 genes. Another 9 shell formation-related genes in L and S were
      examined by qPCR: 1 gene was expressed more highly in L, 5 genes were expressed
      more highly in S and no difference was found for the remaining 3 genes. Some
      genes related to growth and development, shell formation and reproduction were
      expressed more highly in S compared to L. This phenomenon could be explained by
      "catch-up growth". The results of this study will help toward a comprehensive
      understanding of the complexity of differential growth between P. fucata
      individuals and provide valuable information for future research.

PMID- 24440294
TI  - The first Japanese case of the arthrochalasia type of Ehlers-Danlos syndrome with
      COL1A2 gene mutation.
AB  - This is the first report for a Japanese case of arthrochalasia type of Ehlers
      Danlos syndrome (EDS). A 46-year-old woman consulted us for joint hypermobility
      and skin hyperextensibility that had been present soon after birth. There was no
      family history of a similar disease. She was diagnosed as having bilateral
      congenital hip dislocation and bilateral habitual shoulder dislocation at her
      childhood. Her skin was velvety, doughy and hyperextensible. She showed
      hypermobility of the joints of the hands and feet and generalized joint laxity,
      with no evidence of scoliosis. Electrophoretic analysis of collagenous proteins
      revealed the presence of an additional band in the position of pNalpha2(I) in the
      sample from culture medium of the patient fibroblasts. Analysis of the alpha2
      chains of type I collagen gene, COL1A2, showed a heterozygous G to T transition
      at the +1 position of the exon 6 donor splice site (c.279+1G>T). This mutation
      resulted in skipping of exon 6, which leads to deficient processing of the amino
      terminal end of proalpha2(I) chains of type I collagen. Based on these findings,
      we made a diagnosis of the arthrochalasia type of EDS, which corresponds to EDS
      type VIIB in the former classification.

PMID- 24440295
TI  - Selective inhibition of Leishmania donovani by active extracts of wild mushrooms
      used by the tribal population of India: An in vitro exploration for new leads
      against parasitic protozoans.
AB  - The study was intended at evaluating the anti-proliferating effect of mushrooms
      used in traditional folklore of Santal tribal population in India against
      Leishmania donovani (MHOM/IN/83/AG83). A total of eighteen extracts, three
      estracts from each mushroom [(80% ethanol extracted; Fa), (water-soluble
      polysaccharide fraction; Fb), (polyphenolic fraction; Fc)], from six wild
      mushrooms were obtained. These extracts were tested against the promastigotes and
      amastigotes for their antileishmanial capacity. Fa fractions (250 MUg/mL) of
      Astraeus hygrometricus and Tricholoma giganteum significantly inhibited the
      growth of L. donovani promastigotes and interfered in lipid biosynthesis.
      Moreover, both fractions induced apoptosis in promastigotes. Water soluble Fb
      fractions of A. hygrometricus, Russula laurocerasi, Russula albonigra,
      Termitomyces eurhizus, Russula delica and polyphenolic Fc fraction of R.
      laurocerasi were found to inhibit the replication of intracellular amastigotes in
      macrophages dose dependently. Significantly, 50% inhibitory concentration of the
      active extracts against intracellular amastigotes induced release of nitric oxide
      and IL-12 in murine macrophages and dendritic cells assay and also found
      considerably non-toxic on murine splenocytes. Results of this study can be used
      as a basis for further phytochemical and pharmacological investigations in the
      effort for search of novel anti-leishmanial leads.

PMID- 24440296
TI  - A transgenic Neospora caninum strain based on mutations of the dihydrofolate
      reductase-thymidylate synthase gene.
AB  - Neospora caninum is an Apicomplexa parasite related to abortion and losses of
      fertility in cattle. The amenability of Toxoplasma gondii and Plasmodium to
      genetic manipulation offers several tools to determine the invasion and
      replication processes, which support posterior strategies related to the combat
      of these diseases. For Plasmodium the use of pyrimethamine as an auxiliary drug
      on malaria treatment has been affected by the rise of resistant strains and the
      analyses on Dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene indicated
      several point mutations. In this work we developed a method for stable insertion
      of genes based on resistance to pyrimethamine. For that, the coding sequence of
      NcDHFR-TS (Dihydrofolate reductase-thymidylate synthase) was point mutated in two
      amino acids, generating DHFRM2M3. The DHFRM2M3 flanked by the promoter and 3'UTR
      of Ncdhfr-ts (Ncdhfr-DHFRM2M3) conferred resistance to pyrimethamine after
      transfection. For illustration of stability and expression, the cassette Ncdhfr
      DHFRM2M3 was ligated to the reporter gene Lac-Z (beta-galactosidase enzyme)
      controlled by the N. caninum tubulin promoter and was transfected and selected in
      N. caninum. The cassette was integrated into the genome and the selected
      tachyzoites expressed Lac-Z, allowing the detection of tachyzoites by the CPRG
      reaction and X-gal precipitation. The obtainment of transgenic N. caninum
      resistant to pyrimethamine confirms the effects on DHFR-TS among the Apicomplexa
      members and will support future approaches on pholate inhibitors for N. caninum
      prophylaxis. The construction of stable tachyzoites based on vectors with N.
      caninum promoters initiates the molecular manipulation of this parasite
      independently of T. gondii.

PMID- 24440297
TI  - The accumulation of macrophages expressing myeloid-related protein 8 (MRP8) and
      MRP14 in the spleen of BALB/cA mice during infection with Plasmodium berghei.
AB  - Splenomegaly is one of the typical symptoms of malaria. However, the pathogenesis
      of splenic enlargement still remains unclear. Spleen is a major organ for
      clearance of malaria parasites, but excessive response to the parasites can lead
      to splenomegaly. Myeloid-related protein (MRP) 8 and MRP14 are expressed by
      myeloid cells and are regarded as marker proteins of an immature and inflammatory
      subtype of macrophage. Previous studies have demonstrated that accumulation of
      MRP8(+) and MRP14(+) macrophages is associated with the pathological changes
      associated with various inflammatory diseases. In order to elucidate whether
      MRP8(+) and MRP14(+) cells are also involved in splenomegaly during malaria, we
      investigated expression of MRP8 and MRP14 in the spleens of mice infected with
      Plasmodium berghei. The MRP8 and MRP14 levels in the serum were analyzed by
      western blot, which confirmed that these proteins were elevated during infection
      compared with uninfected controls. Enlargement of the spleen was prominent at
      7days of infection, and histological analysis of the spleens demonstrated
      deposition of malaria pigments and accumulation of mononuclear cells.
      Immunohistochemical staining of the tissue revealed the accumulation of cells
      expressing MRP8 and MRP14. In addition, the locations of those cells overlapped
      with CD11b(+) cells in the red pulp. These results suggest that splenomegaly in
      malaria is partly due to the accumulation of MRP8(+) and MRP14(+) macrophages.

PMID- 24440298
TI  - Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii
      thymidylate synthase-dihydrofolate reductase.
AB  - The parasite Toxoplasma gondii can lead to toxoplasmosis in those who are
      immunocompromised. To combat the infection, the enzyme responsible for nucleotide
      synthesis thymidylate synthase-dihydrofolate reductase (TS-DHFR) is a suitable
      drug target. We have used virtual screening to determine novel allosteric
      inhibitors at the interface between the two TS domains. Selected compounds from
      virtual screening inhibited TS activity. Thus, these results show that allosteric
      inhibition by small drug-like molecules can occur in T. gondii TS-DHFR and pave
      the way for new and potent species-specific inhibitors. 

PMID- 24440299
TI  - Discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4
      tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel gpr119
      agonists.
AB  - We describe the discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4
      tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel agonists of
      GPR119. Previously described aniline 2 had suboptimal efficacy in signaling
      assays using cynomolgus monkey (cyno) GPR119 making evaluation of the target in
      preclinical models difficult. Replacement of the aniline ring with a
      tetrahydroquinoline ring constrained the rotation of the aniline C-N bond and
      gave compounds with increased efficacy on human and cyno receptors. Additional
      optimization led to the discovery of 10, which possesses higher free fraction in
      plasma and improved pharmacokinetic properties in rat and cyno compared to 2. 

PMID- 24440300
TI  - Urokinase-type plasminogen activator expression and Rac1/WAVE-2/Arp2/3 pathway
      are blocked by pterostilbene to suppress cell migration and invasion in MDA-MB
      231 cells.
AB  - Breast cancer is the most common malignancy among females, and cancer invasion
      and metastasis are the leading causes of cancer death in breast cancer patients.
      Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has
      been demonstrated to possess anti-cancer effects. However, inhibitory effects of
      pterostilbene on cell migration and invasion and its underlying mechanisms are
      not fully understood. In this study, we investigated the anti-invasive mechanisms
      of pterostilbene in human breast cancer cell line MDA-MB-231 cells. Pterostilbene
      effectively inhibited serum-induced migration and invasion without affecting the
      viability of breast cancer cells. The mRNA expression and activity of urokinase
      type plasminogen activator (uPA) were markedly reduced by pterostilbene
      treatment. Moreover, pterostilbene attenuated nuclear factor kappaB (NF-kappaB)
      transcriptional activity and DNA binding of NF-kappaB on uPA promoter. In
      addition, pterostilbene significantly impaired the activity of Rac1 and the
      expression of WASP-family verprolin-homologous protein-2 (WAVE-2) and actin
      related protein 2/3 (Arp2/3). Overall, these results suggest that pterostilbene
      caused considerable suppression of cell migration and invasion through blocking
      NF-kappaB-mediated uPA expression and Rac1/WAVE/Arp2/3 pathway. 

PMID- 24440301
TI  - Synthesis of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole moiety:
      their in vitro evaluation against PDE4B.
AB  - A number of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole or
      benzofuran moieties were synthesized by using Pd/C-Cu mediated coupling
      cyclization strategy as a key step. The o-iodoanilides or o-iodophenol were
      coupled with 3-{2-(prop-2-ynyloxy)ethyl}-2H-benzo[e][1,3]oxazin-4(3H)-one using
      10%Pd/C-CuI-PPh3 as a catalyst system and Et3N as a base to give the target
      compounds. All the synthesized compounds were tested for their PDE4B inhibitory
      potential in vitro using a cell based cAMP reporter assay. Some of them showed
      fold increase of the cAMP level when tested at 30 MUM. A representative compound
      showed encouraging PDE4B inhibitory properties that were supported by its docking
      results.

PMID- 24440302
TI  - Synthesis of triazole-functionalized 2-DOS analogues and their evaluation as A
      site binders.
AB  - Aminoglycoside-antibiotics represent important tools for studying the biological
      functions of RNA. An orthogonal protection strategy applied on 2-deoxystreptamine
      (2-DOS) revealed a series of key intermediates that enable its regioselective
      functionalization. Our approach allowed the construction of selected
      representatives of triazole-containing analogues with diverse molecular
      frameworks for biological evaluation regarding their binding and antibacterial
      potencies. 

PMID- 24440303
TI  - CpG/Poly (I:C) mixed adjuvant priming enhances the immunogenicity of a DNA
      vaccine against eastern equine encephalitis virus in mice.
AB  - Eastern equine encephalitis virus (EEEV) poses a serious public health threat in
      many countries. Therefore, developing efficient vaccine against EEEV remains an
      important challenge in the field of disease control. To identify immunogenic
      proteins in EEEV, we constructed an expression vector containing the protein
      coding genes C, E3, E2, 6k, and E1 (pcDNA3.1-C-E). After verifying the target
      gene expression in 293 T cells, we immunized BALB/c mice with the pcDNA3.1-C-E
      vector as a DNA vaccine in conjunction with either CpG or poly (I:C) or a mixture
      of both adjuvants and monitored various aspects of the immune response. After two
      immunizations, the mice vaccinated with antigen plus mixed CpG/poly (I:C)
      adjuvant exhibited significantly stronger IFN-gamma responses and generated high
      level CD4(+) cell responses for the cytokines IL-2, IL-4, and IFN-gamma and
      CD8(+) T cell responses for the cytokines IL-2 and IFN-gamma compared to the mice
      vaccinated with the corresponding antigen plus CpG or poly(I:C) alone. In
      addition, the higher antibody titers against EEEV effectively neutralized the
      EEEV pseudoviruses in the group immunized with antigen plus mixed CpG/poly (I:C)
      adjuvant after tertiary immunization. This study demonstrates that the pcDNA3.1-C
      E plasmids in conjunction with mixed CpG/poly (I:C) adjuvant priming maximize the
      cellular immune response and specific antibody generation in mice. Moreover, this
      mixed adjuvant priming provides a promising strategy for enhancing the immune
      effectiveness of a DNA vaccine against EEEV. 

PMID- 24440304
TI  - Disease control outcomes from analysis of pooled individual patient data from
      five comparative randomised clinical trials of degarelix versus luteinising
      hormone-releasing hormone agonists.
AB  - BACKGROUND: Studies comparing the gonadotropin-releasing hormone antagonist,
      degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate
      differences in outcomes. OBJECTIVE: To assess differences in efficacy and safety
      outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists.
      DESIGN, SETTING, AND PARTICIPANTS: Data were pooled from five prospective, phase
      3 or 3b randomised trials (n=1925) of degarelix and leuprolide or goserelin in
      men requiring androgen deprivation therapy for the treatment of prostate cancer.
      Patients received either 3 mo (n=467) or 12 mo (n=1458) of treatment.
      INTERVENTION: Men were randomised to receive degarelix (n=1266), leuprolide
      (n=201), or goserelin (n=458). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards
      model, adjusted for disease-related baseline factors, to estimate hazard ratios
      (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude
      incidences of adverse events. RESULTS AND LIMITATIONS: Prostate-specific antigen
      (PSA) progression-free survival (PFS) was improved in the degarelix group (HR:
      0.71; p=0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA
      PFS was 0.74 (p=0.052). Overall survival (OS) was higher in the degarelix group
      (HR: 0.47; p=0.023). OS was particularly improved with degarelix in patients with
      baseline testosterone levels >2 ng/ml (HR: 0.36; p=0.006). In terms of disease
      related adverse events, there were, overall, fewer joint-related signs and
      symptoms, musculoskeletal events, and urinary tract events in the degarelix
      group. CONCLUSIONS: These data indicate clinical benefits with degarelix,
      including a significant improvement in PSA PFS and OS, as well as reduced
      incidence of joint, musculoskeletal, and urinary tract adverse events, compared
      with LHRH agonists.

PMID- 24440305
TI  - Re: Willem M. Brinkman, Irene M. Tjiam, Barbara M.A. Schout, et al. Results of
      the European Basic Laparoscopic Urological Skills examination. Eur Urol
      2014;65:490-6.

PMID- 24440307
TI  - Promising roles of mammalian E2Fs in hepatocellular carcinoma.
AB  - In mammalian cells, E2F family of transcription factors (E2Fs) traditionally
      modulates assorted cellular functions related to cell cycle progression,
      proliferation, apoptosis and differentiation. Eight members, E2F1 E2F8 have been
      recognized of this family so far, and the members of this family are generally
      divided into activator E2F (E2F1--E2F3a), repressor E2F (E2F3b--E2F5) and
      inhibitor E2F (E2F6--E2F8) subclasses based on their structur-e and function.
      Studies have showed that the mammalian E2F family members represent a recent
      evolutionary adaptation to malignancies besides hepatocellular carcinoma (HCC),
      and a growing body of evidence has validated that the individual members of the
      family develop a close relationship with HCC. E2F1 was identified to play
      overlapping roles in HCC, while E2F2--E2F8 (except E2F6 and E2F7) showed to be
      tumor-promoter in HCC. However, the mechanism underlying the mammalian E2Fs
      associated with HCC is still unknown and needs further research. The aim of this
      review is to sum up the collective knowledge of E2F family and the roles of each
      member of this family in HCC. Moreover, we will discuss some novel therapeutic
      target for HCC based on the complicated functions of mammalian E2Fs. 

PMID- 24440308
TI  - Palmitoylated transmembrane adaptor proteins in leukocyte signaling.
AB  - Transmembrane adaptor proteins (TRAPs) are structurally related proteins that
      have no enzymatic function, but enable inducible recruitment of effector
      molecules to the plasma membrane, usually in a phosphorylation dependent manner.
      Numerous surface receptors employ TRAPs for either propagation or negative
      regulation of the signal transduction. Several TRAPs (LAT, NTAL, PAG, LIME, PRR7,
      SCIMP, LST1/A, and putatively GAPT) are known to be palmitoylated that could
      facilitate their localization in lipid rafts or tetraspanin enriched
      microdomains. This review summarizes expression patterns, binding partners,
      signaling pathways, and biological functions of particular palmitoylated TRAPs
      with an emphasis on the three most recently discovered members, PRR7, SCIMP, and
      LST1/A. Moreover, we discuss in silico methodology used for discovery of new
      family members, nature of their binding partners, and microdomain localization. 

PMID- 24440306
TI  - Importin beta-dependent nuclear import of TopBP1 in ATR-Chk1 checkpoint in
      Xenopus egg extracts.
AB  - TopBP1, a multiple-BRCT-containing protein, plays diverse functions in DNA
      metabolism including DNA replication, DNA damage response and transcriptional
      regulation. The cytoplasmic localization of TopBP1 has been found to be
      associated with breast cancer susceptibility in clinical studies, suggesting the
      biological significance of TopBP1's sub-cellular localization. However, it
      remains elusive how TopBP1 is shuttled into nucleus and recruited to chromatin
      under normal or stressful conditions. Taking advantage of Xenopus egg extract, we
      identified Importin beta as a new interacting protein of the TopBP1 C-terminus.
      We verified the TopBP1-Importin beta association via GST pulldown and
      coimmunoprecipitation assays. We then demonstrated that TopBP1's C-terminal motif
      (designated as CTM, 23 amino acids) containing a putative NLS (nuclear
      localization signal) was required for Importin beta interaction and that CT100 of
      Importin beta (100 amino acids of extreme C-terminus of Importin beta) was
      required for TopBP1 interaction. Further structure-function analysis reveals that
      the CTM of TopBP1 is essential for TopBP1's nuclear import and subsequent
      chromatin recruitment, thereby playing important roles in DNA replication and
      mitomycin C (MMC)-induced Chk1 phosphorylation. In addition, Importin beta
      specific inhibitor importazole inhibits TopBP1's nuclear import and the MMC
      induced Chk1 phosphorylation. With ongoing DNA replication, the Importin beta
      dependent nuclear import of TopBP1 was indeed required for the MMC-induced Chk1
      phosphorylation. Our data also suggest that checkpoint activation requires more
      TopBP1 than DNA replication does. The requirement of TopBP1's CTM motif for ATR
      Chk1 checkpoint can be bypassed in a nucleus-free AT70 system. Taken together,
      our findings suggest that the CTM motif-mediated TopBP1 shuttling into nucleus
      via Importin beta plays an important role in the ATR-Chk1 checkpoint signaling in
      Xenopus egg extracts. 

PMID- 24440309
TI  - CK2 involvement in ESCRT-III complex phosphorylation.
AB  - The multivesicular body (MVB) sorting pathway is a mechanism for delivering
      transmembrane proteins into the lumen of the lysosome for degradation. ESCRT-III
      is the final complex in the pathway that assembles on endosomes and executes
      membrane scission of intraluminal vesicles. In addition, proteins of this complex
      are involved in other topologically similar processes such as cytokinesis, virus
      egress and autophagy. Here we show that protein kinase CK2alpha is involved in
      the phosphorylation of the ESCRT-III subunits CHMP3 and CHMP2B, as well as of
      VPS4B/SKD1, an ATPase that mediates ESCRT-III disassembly. This phosphorylation
      is observed both in vitro and in cells. While we do not observe recruitment of
      CK2alpha to endosomes, we demonstrate the localization of CK2alpha to midbodies
      during cytokinesis. Phosphomimetic and non-phosphorylatable mutants of ESCRT-III
      proteins can still bind endosomes and localize to midbodies, indicating that
      CK2alpha does not regulate ESCRT-III localization. Finally, we analyzed two
      cellular functions where CHMP3, CHMP2B and VPS4 are known to be involved,
      epidermal growth factor degradation and cytokinetic abscission. We demonstrate
      that the former is impaired by CK2alpha downregulation whereas the latter is not
      affected. Taken together, our results indicate that CK2alpha regulates the
      function of ESCRT-III proteins in MVB sorting. 

PMID- 24440310
TI  - "Structural characterization of the minimal segment of TDP-43 competent for
      aggregation".
AB  - TDP-43 is a nuclear protein whose abnormal aggregates are implicated in ALS and
      FTLD. Recently, an Asn/Gln rich C-terminal segment of TDP-43 has been shown to
      produce aggregation in vitro and reproduce most of the protein's pathological
      hallmarks in cells, but little is known about this segment's structure. Here, CD
      and 2D heteronuclear NMR spectroscopies provide evidence that peptides
      corresponding to the wild type and mutated sequences of this segment adopt
      chiefly disordered conformations that, in the case of the wild type sequence,
      spontaneously forms a beta-sheet rich oligomer. Moreover, MD simulation provides
      evidence for a structure consisting of two beta-strands and a well-defined, yet
      non-canonical structural element. Furthermore, MD simulations of four
      pathological mutations (Q343R, N345K, G348V and N352S) occurring in this segment
      predict that all of them could affect this region's structure. In particular, the
      Q343R variant tends to stabilize disordered conformers, N345K permits the
      formation of longer, more stable beta-strands, and G348V tends to shorten and
      destabilize them. Finally, N352S acts to alter the beta-stand register and when
      S352 is phosphorylated, it induces partial unfolding. Our results provide a
      better understanding of TDP-43 aggregation process and will be useful to design
      effectors capable to modulate its progression. 

PMID- 24440311
TI  - Enteroscopy for the early detection of small bowel tumours in at-risk celiac
      patients.
AB  - BACKGROUND: A subset of celiac patients shows a high risk for small bowel
      malignancies. AIMS: To select celiac patients considered at risk and evaluate the
      diagnostic yield of enteroscopy in this context. METHODS: Celiac patients were
      enrolled from a tertiary referral centre during the period June 2011-June 2013,
      based on the following criteria: (i) patients diagnosed when aged 50+ and with
      poor response to gluten-free dieting; (ii) low dietary compliance; (iii) alarm
      symptoms. The patients underwent small bowel capsule endoscopy and/or double
      balloon enteroscopy. Control populations were represented by the 165 non-celiac
      patients undergoing capsule endoscopy for obscure gastrointestinal bleeding, and
      the 815,362-strong population of the Italian province of Varese as a registered
      cohort. RESULTS: Fifty-three patients (19% males, mean age 43.6+/-17.4 years)
      were evaluated. Two jejunal adenocarcinomas and one ileal neuro-endocrine tumour
      were diagnosed by enteroscopy (the diagnostic yield for malignancies in the
      selected population being 5.7%). In the non-celiac controls the detection rate of
      small bowel tumours by capsule endoscopy was 0.6% (P=0.04). When compared to the
      registered population, the relative risk for intestinal malignancy was 1282 (95%
      CI, 407-4033; P<0.0001). CONCLUSIONS: Capsule endoscopy and double-balloon
      enteroscopy can be considered for early disease management of a subset of celiac
      patients.

PMID- 24440312
TI  - Molecular mechanisms of stem cell therapy in alcoholic liver disease.
AB  - Alcoholic liver disease affects a great number of people worldwide. With limited
      therapeutic options, stem cell therapy offers significant potential for these
      patients. To date, a limited number of clinical trials have produced transient
      clinical responses to cell therapy in patients with alcoholic liver disease. Stem
      cell therapy to reorganize the postnatal liver is an important theme and mission
      for patients with chronic liver disorders including alcoholic liver injury. We
      therefore should redevelop the evidence of cell-based liver regeneration therapy,
      focusing on targets (disease, patient's status and hepatic function), materials
      (cells, cytokines and genes), and methodology (stem cell types and their derived
      microparticles, transplantation route, implantation technology and tissue
      engineering). In this review, we summarize the recent findings regarding the
      experimental and clinical use of mesenchymal and liver stem cells, focusing
      mainly on the treatment of alcoholic liver disorders and their relevance in the
      field of regenerative medicine, and advances on the role of microvesicles and
      exosomes in this process. We discuss new advances in stem cell therapy from liver
      regeneration to liver re-organization, which is involved in the recent progress
      of on-going clinical trials, basic research in stem cell therapy and liver
      regeneration, and updated exosomes/microvesicles recovery/repairing technology. 

PMID- 24440313
TI  - Adiponectin and peroxisome proliferator-activated receptor-gamma gene
      polymorphisms and gene-gene interactions with type 2 diabetes.
AB  - AIMS: To investigate whether gene polymorphisms of both adiponectin and
      peroxisome proliferator-activated receptor gamma (PPARgamma) influence type 2
      diabetes mellitus (T2DM) respectively in the Han people of the Wenzhou region of
      China and whether the interaction of gene polymorphism between adiponectin and
      PPARgamma influences T2DM in the same subjects. MAIN METHODS: This study included
      198 patients with T2DM and 255 healthy individuals. Polymerase chain reaction
      restriction fragment length polymorphism analyses were used to detect single
      nucleotide polymorphisms (SNPs). Logistic regression and multifactor
      dimensionality reduction (MDR) methods were used to analyze gene-gene
      interactions. KEY FINDINGS: The frequency distribution of adiponectin SNP11377
      was not different (p=0.792), but the frequency of CC, CG and GG genotypes showed
      the difference between two groups (T2DM: 57.1%, 33.3%, and 9.6%; control: 53.7%,
      41.6%, and 4.7%, respectively; p=0.047). Adiponectin SNP45, SNP276 and PPAR gamma
      SNPp12a were equally distributed between the two groups (p=0.586, 0.119, 0.437,
      respectively), and there were no significant differences in genotype frequencies
      between the two groups (p=0.751, 0.144, 0.479, respectively). Linkage
      disequilibrium existed between SNP11377 and SNP45 (p<0.001) and SNP45 and SNP276
      (p<0.001). Haplotype analyses showed no significant differences between the T2DM
      and control groups. According to the logistic regression and MDR gene-gene
      interaction analyses, SNP11377GG and SNP276GT interactions increased the risk of
      T2DM (odds ratio=6.984, p=0.012). SIGNIFICANCE: Adiponectin SNP11377 and SNP276
      gene-gene interactions are associated with the increased risk of T2DM in this
      population.

PMID- 24440314
TI  - Stop "Early repolarization syndrome", start "Haissaguerre syndrome".

PMID- 24440315
TI  - ICE proceedings in digitized era.

PMID- 24440316
TI  - Translational research - evidence to enhance the quality of pediatric nursing
      practice and health outcomes for children and their families.

PMID- 24440317
TI  - Antidepressant-like effects of Xiaochaihutang in a rat model of chronic
      unpredictable mild stress.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT) has been used in China for
      thousands of years to treat "Shaoyang syndrome", which involves depressive-like
      symptoms. However, few studies have investigated its antidepressant effects and
      pharmacological mechanism of action. The present study was designed to confirm
      the antidepressant effect of XCHT using a chronic unpredictable mild stress
      (CUMS) model and explore its potential mechanism of action by investigating the
      monoamine neurotransmitters (dopamine and 5-hydroxytryptamine) and neurotrophins
      (BDNF and NGF). MATERIALS AND METHODS: The CUMS model was established in rats,
      and the antidepressant effect of XCHT (0.6, 1.7 and 5mg/kg/day, given by gastric
      gavage for 4 weeks) was investigated using the open field test (OFT), food
      consumption test and sucrose preference test. The concentrations of 5-HT and DA
      in the hippocampus were measured by high performance liquid chromatography with
      electrochemical detection (HPLC-ECD). The expressions of brain-derived
      neurotrophic factor (BDNF), nerve growth factor (NGF), and their receptors
      tyrosine receptor kinase B (TrkB) and tyrosine receptor kinase A (TrkA) in the
      hippocampus were measured by immunohistochemical staining analysis. RESULTS: CUMS
      caused a significant decrease in OFT, food consumption and sucrose preference in
      rats, and these depression-like behaviors were significantly improved by XCHT
      (1.7 and 5 g/kg/day). Moreover, XCHT significantly increased the concentrations
      of 5-HT (0.6 and 5 g/kg/day) and DA (5 g/kg/day), and improved the BDNF, NGF,
      TrkB and TrkA expressions in the hippocampus (1.7 and 5 g/kg/day), which was
      reduced in CUMS rats. CONCLUSION: The results obtained suggested that XCHT may
      have therapeutic actions on depression-like behavior induced by CUMS in rats
      possibly mediated by increasing the monoamine neurotransmitter concentration and
      neurotrophin expression in the hippocampus.

PMID- 24440318
TI  - Hemorrhagic Fever with Renal Syndrome in the New, and Hantavirus Pulmonary
      Syndrome in the Old World: paradi(se)gm lost or regained?
AB  - Since the first clinical description in 1994 of the so-called "Hantavirus
      Pulmonary Syndrome" (HPS) as a "newly recognized disease", hantavirus infections
      have always been characterized as presenting in two distinct syndromes, the so
      called "Hemorrhagic Fever with Renal Syndrome" (HFRS) in the Old World, with the
      kidney as main target organ, in contrast to HPS in the New World, with the lung
      as main target organ. However, European literature mentions already since 1934 a
      mostly milder local HFRS form, aptly named "nephropathia epidemica" (NE), and
      caused by the prototype European hantavirus species Puumala virus (PUUV). Several
      NE reports dating from the 1980s and early 1990s described already non
      cardiogenic HPS-like lung involvement, prior to any kidney involvement, and
      increasing evidence is now mounting that a considerable clinical overlap exists
      between HPS and HFRS. Moreover, growing immunologic insights point to common
      pathologic mechanisms, leading to capillary hyperpermeability, the cardinal
      feature of all hantavirus infections, both of the New and Old World. It is now
      perhaps time to reconsider the paradigm of two "different" syndromes caused by
      viruses of the same Hantavirus genus in the same Bunyaviridae family, and to
      agree on a common, more logical disease denomination, such as simply and briefly
      "Hantavirus fever". 

PMID- 24440319
TI  - Primary and secondary intralymphatic histiocytosis.
AB  - BACKGROUND: Intralymphatic histiocytosis (IH) is a rare condition often
      associated with systemic disease. A benign condition, clinical presentations can
      vary greatly and its cause is largely unknown. Histologically, there are
      macrophages within distended lymphatic vessels, although this can be an
      incidental finding or the primary abnormality. OBJECTIVE: We present a series of
      7 cases of IH with and without disease associations, and a review of the
      literature. We propose IH as either primary (without associated conditions) or
      secondary (associated with systemic disease). METHODS: This was a retrospective
      collection of patients whose skin biopsy specimens revealed intralymphatic
      collections of histiocytes. We reviewed their clinical presentation, disease
      associations, and staining of slides with CD68 in all cases, D2-40 in 5 cases,
      and HLA-DR in 4 cases. RESULTS: Clinical features were highly variable, and not
      all cases were associated with systemic disease. One case had admixed reactive
      angioendotheliomatosis. All 4 cases stained for HLA-DR showed strong expression
      by the intralymphatic macrophages. LIMITATIONS: Retrospective analysis and
      limited numbers are limitations. CONCLUSION: IH is not always associated with
      systemic disease although macrophage activation nevertheless implies immune
      activation.

PMID- 24440320
TI  - Emergence and diversity of begomoviruses infecting solanaceous crops in East and
      Southeast Asia.
AB  - Over the past three decades diseases caused by whitefly-transmitted geminiviruses
      (begomoviruses) have emerged to be important constraints to the production of
      solanaceous crops, particularly tomato (Solanum lycopersicum) and peppers
      (Capsicum spp.), in many tropical and subtropical regions of the world. The most
      studied of these is Tomato yellow leaf curl virus (TYLCV), which has spread to
      many other areas from its likely origin in the Mediterranean basin region. The
      virus is usually associated with the polyphagous and virus-vectoring-efficient B
      biotype of its vector whitefly (Bemisia tabaci). However, in Southeast and East
      Asia, a wide variety of distinct local begomovirus species have been identified
      from tomato and pepper crops over this period, and TYLCV was detected in Japan
      only in about 1996, China in 2006 and Korea in 2008, despite B-biotype whiteflies
      being present in several of the countries of the region since at least the early
      1990s. Continental Southeast Asia appears to be a major center of diversity for
      begomoviruses and some species may have spread across the region; Tomato yellow
      leaf curl Thailand virus (TYLCTHV) appears to have spread from the Thailand
      Myanmar region into southern China and is now displacing the local tomato
      infecting species in Taiwan, and Tomato yellow leaf curl Kanchanaburi virus
      (TYLCKaV) appears to have spread from the Thailand-Vietnam region to Java,
      Indonesia. Since many of the native tomato- or pepper-infecting begomoviruses and
      associated satellite DNAs have also been detected in local weed species, it seems
      likely that their ancestors originated in these weed hosts, but with the
      expansion and intensification of tomato and pepper production in the region,
      there was selection for recombinant or mutant forms with greater virulence on
      tomato and/or pepper. Expansion and intensification of these crops may also have
      resulted in increased populations of local, and if present, B- or Q-biotype
      whiteflies, aiding the increase and spread of local begomovirus species.

PMID- 24440321
TI  - Author response.

PMID- 24440322
TI  - Depressive symptoms and the incidence of adult-onset asthma in African American
      women.
AB  - BACKGROUND: Some evidence suggests that depression may increase the risk of adult
      onset asthma. No data are available for African American women, in whom the
      prevalence of depression and asthma is high. OBJECTIVE: To conduct prospective
      analyses of the relation of depressive symptoms to asthma incidence in the Black
      Women's Health Study, a prospective cohort of US black women followed since 1995
      with mailed biennial questionnaires. METHODS: Of 31,848 participants followed
      from 1999 to 2011, 771 reported incident asthma. Depressive symptoms were
      ascertained on 1999 and 2005 follow-up questionnaires with the Center for
      Epidemiological Studies-Depression Scale (CES-D). Participants rated the
      frequency of 20 symptoms. A score was calculated by summing the responses to all
      questions. Cox regression models were used to derive incidence rate ratios and
      95% confidence intervals for 4 categories of the CES-D score in relation to
      incident asthma, adjusted for body mass index, smoking, and other covariates.
      RESULTS: The multivariable incidence rate ratio in the highest category of CES-D
      score (>= 33) compared with the lowest (<16) was 2.08 (95% confidence interval
      1.58-2.74), with a significant trend (P < .0001). The incidence rate ratio was
      higher in women who took antidepressants, were current or former smokers, were
      not obese, and were at least 40 years old, although there were no statistically
      significant interactions. CONCLUSION: A positive association was observed between
      CES-D score and the incidence of adult-onset asthma. If the hypothesis is
      confirmed, depression could contribute substantially to the burden of asthma in
      adults.

PMID- 24440323
TI  - Author response.

PMID- 24440324
TI  - Utilization of evidence-based therapy for acute coronary syndrome in high-income
      and low/middle-income countries.
AB  - Limited data exist regarding the management of patients with acute coronary
      syndrome (ACS) in high-income countries compared with low/middle-income
      countries. We aimed to compare in-hospital trends of revascularization and
      prescription of medications at discharge in patients with ACS from high-income
      (Canada and United States) and low/middle-income (India, Iran, Pakistan, and
      Tunisia) countries. Data from a double-blind, placebo-controlled, randomized
      trial investigating the effect of bupropion on smoking cessation in patients
      after an enzyme-positive ACS was used for our study. A total of 392 patients, 265
      and 127 from high-income and from low/middle-income countries, respectively, were
      enrolled. Patients from high-income countries were older, and were more likely to
      have diagnosed hypertension and dyslipidemia. During the index hospitalization,
      patients from high-income countries were more likely to be treated by
      percutaneous coronary intervention (odds ratio [OR] 19.7, 95% confidence interval
      [CI] 10.5 to 37.0). Patients with ST elevation myocardial infarction from high
      income countries were more often treated by primary percutaneous coronary
      intervention (OR 16.3, 95% CI 6.3 to 42.3) in contrast with thrombolytic therapy
      (OR 0.24, 95% CI 0.14 to 0.41). Patients from high-income countries were also
      more likely to receive evidence-based medications at discharge (OR 2.32, 95% CI
      1.19 to 4.52, a composite of aspirin, clopidogrel, and statin). In conclusion,
      patients with ACS in low/middle-income countries were less likely to be
      revascularized and to receive evidence-based medications at discharge. Further
      studies are needed to understand the underutilization of procedures and evidence
      based medications in low/middle-income countries.

PMID- 24440325
TI  - Relation between coronary calcium and major bleeding after percutaneous coronary
      intervention in acute coronary syndromes (from the Acute Catheterization and
      Urgent Intervention Triage Strategy and Harmonizing Outcomes With
      Revascularization and Stents in Acute Myocardial Infarction Trials).
AB  - Percutaneous coronary intervention (PCI) of calcified coronary lesions has been
      associated with increased rates of adverse ischemic events. However, the
      potential association between the presence and severity of calcific deposits and
      bleeding complications has yet to be investigated. Data from 6,855 patients with
      non-ST-segment elevation acute coronary syndrome (NSTEACS) or ST-segment
      elevation myocardial infarction (STEMI) treated with PCI were pooled from 2 large
      scale randomized controlled trials-Acute Catheterization and Urgent Intervention
      Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in
      Acute Myocardial Infarction. Patients were stratified into 3 groups according the
      grade of target PCI lesion calcium (none to mild, moderate, and severe) as
      assessed by an independent angiographic core laboratory. Thirty-day bleeding
      event rates were assessed and compared among groups. In the total cohort
      undergoing PCI, none-to-mild target lesion calcium was found in 4,665 patients
      (68.1%), moderate target lesion calcium in 1,788 patients (26.1%), and severe
      target lesion calcium in 402 patients (5.9%). The 30-day rates of non-coronary
      artery bypass graft surgery major bleeding increased significantly with each
      degree of coronary calcium (none to mild = 5.9%, moderate = 7.2%, and severe =
      11.2%, p = 0.0003). By multivariable analysis, presence of severe calcium was an
      independent predictor of non-coronary artery bypass graft major bleeding after
      PCI (hazard ratio 1.54, 95% confidence interval 1.09 to 2.17, p = 0.01). In
      conclusion, in patients undergoing PCI for non-ST-segment elevation acute
      coronary syndrome and ST-segment elevation myocardial infarction, target lesion
      coronary calcium was an independent predictor of major bleeding events. Further
      studies are needed to elucidate mechanisms underlying this finding and to
      optimize treatment of this high-risk population.

PMID- 24440326
TI  - Relation of prenatal diagnosis with one-year survival rate for infants with
      congenital heart disease.
AB  - Prenatal diagnosis of congenital heart defects (CHDs) is increasingly common, but
      it is still unclear whether it translates to improved postoperative outcomes. We
      performed a retrospective cohort study of all infants (aged <1 year) who
      underwent surgery for CHDs from 2006 to 2011 at a single institution. Primary
      outcomes were in-hospital and 1-year mortality rates. Secondary outcomes were
      readmission within 30 days of discharge, postoperative length of intensive care
      unit and hospital stay, unplanned reoperation, and extracorporeal membrane
      oxygenation use. We used chi-square analyses, Wilcoxon rank-sum tests, Kaplan
      Meier survival curves, and adjusted Cox proportional hazards models to compare
      outcomes. Of the 1,642 patients with CHDs, 539 (33%) were diagnosed prenatally.
      Patients with prenatal diagnoses were of a younger age and less weight at the
      time of surgery, had greater Risk Adjustment for Congenital Heart Surgery scores,
      and were more likely to be white, to have an identified syndrome, or to be born
      at term. Compared with those diagnosed postnatally, those diagnosed prenatally
      had a significantly higher unadjusted 1-year mortality rate (11% vs 5.5%,
      respectively, p = 0.03). Controlling for weight, surgical severity, race, age at
      surgery, prematurity, and the presence or absence of genetic syndrome, patients
      with prenatal diagnoses had significantly greater mortality at 1 year (adjusted
      hazard ratio 1.5, p = 0.03), as well as significantly longer intensive care unit
      and hospital stays. Infants with CHDs diagnosed prenatally had worse outcomes
      compared with those diagnosed postnatally. Prenatal diagnosis likely captures
      patients with more severe phenotypes within given surgical risk categories and
      even within diagnoses and thus may be an important prognostic factor when
      counseling families.

PMID- 24440327
TI  - Effect of digoxin on shocks in cardiac resynchronization therapy-defibrillator
      patients with coronary artery disease.
AB  - Digoxin provides symptomatic relief in patients with systolic heart failure, yet
      it has potential proarrhythmic mechanisms and has not been formally studied in
      patients with cardiac resynchronization therapy-defibrillators (CRT-Ds). We
      evaluated the association between digoxin use and appropriate tachyarrhythmia
      therapy in patients with CRT-D with advanced heart failure, analyzing the
      incidence of appropriate device therapies and overall survival in 350 consecutive
      primary prevention recipients with CRT-D with baseline left ventricular ejection
      fraction (LVEF) <=35%, non-right bundle-branch block native QRS complex >=120 ms,
      New York Heart Association III to IV heart failure, and significant coronary
      artery disease. Digoxin was prescribed in 162 patients (46%) at discharge from
      CRT-D implant. Over 48 +/- 32 months of follow-up, 59 patients (17%) received >=1
      appropriate shock. Digoxin therapy was associated with shorter time to first
      shock in intention-to-treat (corrected hazard ratio 2.18, 95% confidence interval
      1.23 to 3.87, p = 0.007) and on-treatment analysis (corrected hazard ratio 2.27,
      95% confidence interval 1.27 to 4.07, p = 0.006). Patients prescribed digoxin had
      a lower baseline LVEF, and digoxin therapy was associated with increased risk of
      shocks only in patients with LVEF <22% (median); there was no increased risk in
      patients with LVEF >=22%. Overall survival and incidence of antitachycardia
      pacing were similar regardless of digoxin therapy. In conclusion, digoxin therapy
      is associated with increased likelihood of appropriate CRT-D shocks for rapid
      ventricular arrhythmias in primary prevention patients with coronary artery
      disease, and this risk appears to be most evident in patients with more severe
      baseline LV dysfunction. Digoxin use should be reexamined prospectively in
      patients with CRT-D.

PMID- 24440328
TI  - Prognostic value of myocardial ischemic electrocardiographic response in patients
      with normal stress echocardiographic study.
AB  - The prognostic value of ST-segment depression on exercise electrocardiogram
      (eECG) in the setting of a normal wall motion response in a stress
      echocardiographic study is not well defined. The aim of the study was to compare
      outcomes among patients with normal wall motion during stress echocardiography
      with and without ischemic exercise electrocardiographic changes. A total of 4,233
      patients underwent stress echocardiography from 2007 to 2010. The primary
      outcomes were a composite of all-cause mortality and myocardial infarction.
      Coronary revascularization was a secondary outcome. A Cox regression model was
      used for the primary analysis. Ischemic exercise electrocardiographic changes
      were defined as ST-segment depression of at least 1 mm, on at least 3 consecutive
      beats, and in at least 2 contiguous leads. A normal stress echocardiogram was
      present in 2,975 patients; of them, 2,228 (74%) had a normal eECG and 747 (26%)
      had ischemic changes on eECG. Patients with and without ischemic changes during
      exercise electrocardiography were similar in age and gender. At 4-years follow
      up, 36 patients (2.8%) with a normal eECG experienced a primary end point versus
      12 patients (1.9%) in the group with an ischemic exercise electrocardiographic
      response (p = 0.56). The rate of coronary revascularization was similar between
      the groups (7.0% and 5.7%, respectively, p = 0.2). There were no differences in
      the primary outcomes of patients with and without exercise electrocardiographic
      changes and normal stress echocardiogram (hazard ratio 1.33, 95% confidence
      interval 0.69 to 2.58). In conclusion, a normal wall motion response even in the
      setting of an ischemic exercise electrocardiographic response portends a benign
      prognosis in patients undergoing stress echocardiography.

PMID- 24440329
TI  - Usefulness of right ventricular dysfunction to predict new-onset atrial
      fibrillation following coronary artery bypass grafting.
AB  - Postoperative atrial fibrillation (AF) is a serious yet common complication after
      coronary artery bypass grafting (CABG) surgery. Risk factors for postoperative AF
      have been identified, including echocardiographic parameters, and these are
      relied on to implement preventative strategies that reduce the incidence of AF.
      There has yet to be a study examining the impact of echocardiographic right-sided
      cardiac parameters on the prediction of postoperative AF. Thus, a panel of right
      sided cardiac parameters was measured in a cohort of patients undergoing isolated
      CABG surgery, excluding those who did not have echocardiographic assessment
      within 30 days before surgery and those with any history of AF. The primary
      outcome was postoperative AF defined as any episode of AF requiring treatment
      during the index hospitalization. Postoperative AF occurred in 197 of 768
      patients (25.6%); these were older and more likely to have hypertension and
      chronic kidney disease. After adjustment for clinical and echocardiographic
      variables, left atrial volume index >=34 ml/m(2) (odds ratio [OR] 1.98, 95%
      confidence interval [CI] 1.36 to 2.87), abnormal right ventricular myocardial
      performance index (OR 1.50, 95% CI 1.01 to 2.24), and advancing age (OR 1.05, 95%
      CI 1.03 to 1.07) were found to be independent predictors of postoperative AF. In
      conclusion, right ventricular myocardial performance index is a novel predictor
      of postoperative AF in patients undergoing isolated CABG surgery and appears to
      be additive to established risk factors such as age and left atrial volume.

PMID- 24440330
TI  - Comparison of the safety and feasibility of arrhythmia ablation using the Amigo
      Robotic Remote Catheter System versus manual ablation.
AB  - The aim of this study is to evaluate the safety and feasibility of using the
      Amigo Remote Catheter System (RCS) in arrhythmia ablation procedures. Because
      Amigo allows the physician to operate all catheter function outside of the
      radiation field, operator exposure time was also evaluated. This is a
      nonrandomized, prospective clinical trial conducted at 1 site (identifier:
      NCT01834872). The study prospectively enrolled 50 consecutive patients (mean age
      59 +/- 15 years, 72% men) with any type of arrhythmia (23 atrial fibrillation
      ablation, 12 common atrial flutters, 10 patients with other supraventricular
      tachycardia, 4 ventricular tachycardia, and 1 patient with palpitations with no
      arrhythmia induced) referred for catheter ablation, in which we used RCS. Fifty
      matched ablation procedures (mean age 57 +/- 14 years, 70% men) performed during
      the same time period, without RCS, were enrolled into the control group. Acute
      ablation success was 96% with RCS and 98% in the manual group. In only 2 cases,
      the physician switched to manual ablation (1 ventricular tachycardia and 1
      accessory pathway) to complete the procedure. There were no complications related
      to the use of RCS. No differences were observed in total procedure time, total
      fluoroscopy time, or total radiofrequency delivery compared with the manual
      group. In procedures performed with RCS, the operator's fluoroscopy exposure time
      was reduced by 68 +/- 16%. In conclusion, arrhythmia ablation with RCS is safe
      and feasible. Furthermore, it significantly reduces operator's exposure to
      radiation.

PMID- 24440331
TI  - Comparison of intermediate-term outcomes of coronary artery bypass grafting
      versus drug-eluting stents for patients >=75 years of age.
AB  - Several randomized controlled trials and observational studies have compared
      outcomes of percutaneous coronary interventions (PCIs) with drug-eluting stents
      (DESs) and coronary artery bypass grafting (CABG), but they have not thoroughly
      investigated the relative difference in outcomes for patients aged >=75 years. In
      this study, a total of 3,864 patients receiving DES and CABG (1,932 CABG-DES
      pairs) with multivessel coronary disease were propensity matched using multiple
      patient risk factors and were compared with respect to 3 outcomes (mortality,
      stroke/myocardial infarction [MI]/mortality, and repeat revascularization) at 2.5
      years with a mean follow-up of 18 months. The mortality rates (DES/CABG hazard
      ratio 1.06, 95% confidence interval 0.87 to 1.30) and the stroke/MI/mortality
      rates (DES/CABG hazard ratio 1.15, 95% confidence interval 0.97 to 1.38) for the
      2 procedures were not significantly different. Repeat revascularization rates
      were significantly higher for patients who received DESs. In conclusion, older
      patients experienced similar mortality and stroke/MI/mortality rates for CABG and
      PCI with DES, although repeat revascularization rates were higher for patients
      undergoing PCI with DES.

PMID- 24440332
TI  - Meta-analysis of randomized controlled trials on the risk of bleeding with
      dabigatran.
AB  - Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor that has
      been developed as an alternative to vitamin K antagonists (VKAs). However,
      uncertainty remains regarding dabigatran's safety profile with respect to
      bleeding. Our objective was to compare the risk of bleeding and all-cause
      mortality of dabigatran with that of VKAs in a systematic review and meta
      analysis of randomized controlled trials (RCTs). We systematically searched
      MEDLINE, Embase, and the Cochrane Library of clinical trials to identify RCTs
      comparing the bleeding risk of dabigatran (150 mg twice daily) with that of VKAs.
      Included RCTs had treatment duration >=90 days and were published in English or
      French. Data were meta-analyzed using random-effects models. Five RCTs (n =
      20,332) were included in our systematic review. Study populations consisted of
      patients with atrial fibrillation (n = 18,615) and venous thromboembolism (n =
      7,998). When data were pooled across the 4 RCTs (n = 17,466) without overlapping
      populations, dabigatran was not associated with an increased risk of major
      bleeding compared with VKAs (relative risk [RR] 0.92, 95% confidence interval
      [CI] 0.81 to 1.05). Dabigatran was associated with a decreased risk of
      intracranial bleeding (RR 0.40, 95% CI 0.27 to 0.59) but an increased risk of
      gastrointestinal bleeding (RR 1.51, 95% CI 1.23 to 1.84). Dabigatran was also
      associated with a trend toward decreased all-cause mortality (RR 0.90, 95% CI
      0.80 to 1.01). In conclusion, results suggest that dabigatran has a favorable
      safety profile with respect to bleeding compared with VKAs.

PMID- 24440333
TI  - Comparison of force exerted on the sternum during a sneeze versus during low-,
      moderate-, and high-intensity bench press resistance exercise with and without
      the valsalva maneuver in healthy volunteers.
AB  - Sternal precautions are intended to prevent complications after median
      sternotomy, but little data exist to support the consensus recommendations. To
      better characterize the forces on the sternum that can occur during everyday
      events, we conducted a prospective nonrandomized study of 41 healthy volunteers
      that evaluated the force exerted during bench press resistance exercise and while
      sneezing. A balloon-tipped esophageal catheter, inserted through the subject's
      nose and advanced into the thoracic cavity, was used to measure the intrathoracic
      pressure differential during the study activities. After the 1 repetition maximum
      (1-RM) was assessed, the subject performed the bench press at the following
      intensities, first with controlled breathing and then with the Valsalva maneuver:
      40% of 1-RM (low), 70% of 1-RM (moderate), and 1-RM (high). Next, various nasal
      irritants were used to induce a sneeze. The forces on the sternum were calculated
      according to a cylindrical model, and a 2-tailed paired t test was used to
      compare the mean force exerted during a sneeze with the mean force exerted during
      each of the 6 bench press exercises. No statistically significant difference was
      found between the mean force from a sneeze (41.0 kg) and the mean total force
      exerted during moderate-intensity bench press exercise with breathing (41.4 kg).
      In conclusion, current guidelines and recommendations limit patient activity
      after a median sternotomy. Because these patients can repeatedly withstand a
      sneeze, our study indicates that they can withstand the forces from more
      strenuous activities than are currently allowed.

PMID- 24440335
TI  - Appearance commentary from romantic partners: evaluation of an adapted measure.
AB  - The purpose of this study was to evaluate the psychometric properties of the
      Verbal Commentary on Physical Appearance Scale (VCOPAS; Herbozo & Thompson,
      2006b) after modifying it to capture appearance feedback given by romantic
      partners (VCOPAS-P). Women participants (N=248) completed the VCOPAS-P, as well
      as measures of disordered eating, body image dissatisfaction, relationship
      quality, and socially desirable responding. Exploratory factor analysis
      identified the best factor structure for the VCOPAS-P, which contained three
      factors similar to the VCOPAS. Correlations between the VCOPAS-P subscales and
      measures of disordered eating, body image dissatisfaction, relationship quality,
      and social desirability responding demonstrated convergent and discriminant
      validity of the VCOPAS-P. There was a significant positive correlation between
      the negative comments subscale of the VCOPAS-P and the measures of body
      dissatisfaction and weight concern (measured by the EDE-Q). Additionally, VCOPAS
      P subscales reflecting positive comments about appearance and weight were
      associated with greater relationship satisfaction. 

PMID- 24440334
TI  - Redox modification of nuclear actin by MICAL-2 regulates SRF signaling.
AB  - The serum response factor (SRF) binds to coactivators, such as myocardin-related
      transcription factor-A (MRTF-A), and mediates gene transcription elicited by
      diverse signaling pathways. SRF/MRTF-A-dependent gene transcription is activated
      when nuclear MRTF-A levels increase, enabling the formation of transcriptionally
      active SRF/MRTF-A complexes. The level of nuclear MRTF-A is regulated by nuclear
      G-actin, which binds to MRTF-A and promotes its nuclear export. However, pathways
      that regulate nuclear actin levels are poorly understood. Here, we show that
      MICAL-2, an atypical actin-regulatory protein, mediates SRF/MRTF-A-dependent gene
      transcription elicited by nerve growth factor and serum. MICAL-2 induces redox
      dependent depolymerization of nuclear actin, which decreases nuclear G-actin and
      increases MRTF-A in the nucleus. Furthermore, we show that MICAL-2 is a target of
      CCG-1423, a small molecule inhibitor of SRF/MRTF-A-dependent transcription that
      exhibits efficacy in various preclinical disease models. These data identify
      redox modification of nuclear actin as a regulatory switch that mediates SRF/MRTF
      A-dependent gene transcription. 

PMID- 24440336
TI  - Reply: To PMID 23395699.

PMID- 24440338
TI  - Modeling lengthy work-ups in gastrointestinal bleeding.
AB  - Multiple procedures and medical devices are being used in a complex interplay to
      diagnose and treat gastrointestinal bleeding. The aim of the study was to develop
      a mathematical model that helps in estimating the average number of procedures to
      be expected in the general management of gastrointestinal bleeding. The modeling
      process serves as an example of how mathematical analysis in general can be used
      to answer unresolved clinical questions, lead to a better understanding of the
      underlying influences in a disease process, and provide a starting point for
      future clinical trials. The analysis uses a Markov chain to model the transition
      probabilities among consecutive interventions used to find and treat a bleeding
      site. The results show that starting a work-up of gastrointestinal bleeding with
      an esophagogastroduodenoscopy will lead on average to 2.69 procedures per
      patient. Of these expected procedures, 1.46 will be esophagogastroduodenoscopies,
      0.69 colonoscopies, 0.25 video capsule endoscopies, 0.14 double-balloon
      enteroscopies, and 0.14 procedures from interventional radiology. Management
      chains initiated with a colonoscopy result in similar outcomes. Among 10,000
      simulated individual patients, the number of procedures varies between 1 and 16
      consecutive procedures, with 95% of all patients undergoing 6 procedures or less.
      The outcomes of the model suggest that the published success rates of endoscopic
      and radiographic procedures are overly optimistic. The results also point to the
      need to generate clinical data through future studies that more reliably account
      for treatment failures and the interchange among various complementary diagnostic
      modalities. 

PMID- 24440337
TI  - Dietary elimination therapy is an effective option for adults with eosinophilic
      esophagitis.
AB  - BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is an immune-mediated disorder.
      Food elimination is an established treatment for children, but data in adults are
      limited. We aimed to determine the response of adults with EoE to dietary
      therapy. METHODS: This was a retrospective cohort study using the University of
      North Carolina EoE database from 2006 to 2012. Subjects were age 18 and older,
      had EoE by consensus guidelines, and had undergone dietary therapy either with a
      targeted elimination diet or a 6-food elimination diet (SFED). Outcomes were
      symptomatic, endoscopic, and histologic improvement. Demographic, endoscopic,
      symptomatic, and laboratory predictors of response to dietary therapy were
      assessed. RESULTS: Of 31 adults who underwent dietary therapy (mean age, 36 y;
      48% male; 90% white; mean baseline eosinophil count, 78 eos/hpf), 22 had a
      targeted elimination diet and 9 had SFED. Symptoms improved in 71% (68% in
      targeted, 78% in SFED), and endoscopic appearance improved in 54% (53% in
      targeted, 56% in SFED). After dietary therapy, the mean eosinophil count
      decreased to 43 eos/hpf (P = .009). Eleven subjects (39%) responded with fewer
      than 15 eos/hpf (32% in targeted and 56% in SFED; P = .41). No clinical,
      endoscopic, or histologic factors predicted response to dietary therapy. Of the
      11 responders, 9 underwent food re-introduction to identify trigger(s), and 4
      (44%) reacted to dairy, 4 (44%) reacted to eggs, 2 (22%) reacted to wheat, 1
      (11%) reacted to shellfish, 1 (11%) reacted to legumes, and 1 (11%) reacted to
      nuts. CONCLUSIONS: Dietary elimination is a successful treatment modality for
      adults with EoE. Further research should emphasize which factors can predict
      effective dietary therapy.

PMID- 24440339
TI  - The effectiveness of a community-based health promotion program for rural elders:
      a quasi-experimental design.
AB  - OBJECTIVES: A community-based health promotion program (CBHP) might be beneficial
      for the elderly, but evidence is limited. We therefore examined the effect of a
      CBHP on change of lifestyle, physiological indicators and depression score among
      seniors in 2 rural areas. METHODS: A prospective quasi-experimental design
      involved a total of 520 senior participants living in 6 rural villages, who were
      clustered and conveniently assigned to 2 intervention groups. Senior nursing
      students were the interveners for group 1 and community peer supporters for group
      2. The primary outcome measure was the change in health-related behavior measured
      on the geriatric health promotion scale (GHPS). The secondary outcome comprised
      changes in the short form of the Chinese geriatric depression scale (CGDS-15),
      fasting blood sugar, total cholesterol, waist circumference and blood pressure.
      Paired-t test and analysis of covariance were used for statistical inspection.
      RESULTS: Most of the participants were retired farmers or fishermen >75years of
      age who had little education. The total scores and all subscales of GHPS, along
      with some physiological indicators, improved significantly between pretest and
      post-test in both groups. After adjustment for confounders, intervention in group
      1 was more effective than that in group 2 regarding self-protection behaviors.
      Systolic and diastolic blood pressure was significantly lower in group 2.
      CONCLUSIONS: CBHP programs are valuable for improving healthy lifestyle, fasting
      blood sugar, blood pressure and depression score among seniors. The low cost and
      effectiveness of incorporating multidisciplinary resources to help rural elders
      to maintain a healthy status and a healthier lifestyle.

PMID- 24440340
TI  - Supine changes in lung function correlate with chronic respiratory failure in
      myotonic dystrophy patients.
AB  - Quality of life and prognosis of patients with myotonic dystrophy type 1 (MD1)
      often depend on the degree of lung function impairment. This study was designed
      to assess the respective prevalence of ventilatory restriction, hypoxaemia and
      hypercapnia in MD1 patients and to determine whether postural changes in lung
      function could contribute to the early diagnosis of poor respiratory outcome.
      Fifty-eight patients (42.6+/-12.9 years) with MD1 were prospectively evaluated
      from April 2008 to June 2010 to determine their supine and upright lung function
      and arterial blood gases. The prevalence of ventilatory restriction was 36% and
      increased with the severity of muscular disability (from 7.7% to 70.6%). The
      prevalence of hypoxaemia and hypercapnia was 37.9% and 25.9%, respectively.
      Multiple regression analysis showed that the supine fall in FEV1 was the only
      variable associated with ventilatory restriction, hypoxaemia and hypercapnia. Our
      data indicate that supine evaluation of lung function could be helpful to predict
      poor respiratory outcome, which is closely correlated with hypoxaemia and/or
      hypercapnia. 

PMID- 24440341
TI  - PBPK modeling for PFOS and PFOA: validation with human experimental data.
AB  - In recent years, because of the potential human toxicity, concern on
      perfluoroalkyl substances (PFASs) has increased notably with special attention to
      perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS).
      Unfortunately, there is currently an important knowledge gap on the burdens of
      these chemicals in most human tissues, as the reported studies have been mainly
      focused on plasma. In order to overcome these limitations, the use of
      physiologically-based pharmacokinetic (PBPK) models has been extended. The
      present study was aimed at testing an existing PBPK model for their
      predictability of PFOS and PFOA in a new case-study, and also to adapt it to
      estimate the PFAS content in human tissue compartments. Model validation was
      conducted by means of PFOA and PFOS concentrations in food and human drinking
      water from Tarragona County (Catalonia, Spain), and being the predicted results
      compared with those experimentally found in human tissues (blood, liver, kidney,
      liver and brain) of subjects from the same area of study. The use of human
      derived partition coefficient (Pk) data was proven as more suitable for
      application to this PBPK model than rat-based Pk values. However, the uncertainty
      and variability of the data are still too high to get conclusive results.
      Consequently, further efforts should be carried out to reduce parametric
      uncertainty of PBPK models. More specifically, a deeper knowledge on the
      distribution of PFOA and PFOS within the human body should be obtained by
      enlarging the number of biological monitoring studies on PFASs. 

PMID- 24440342
TI  - Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs
      their energy metabolism.
AB  - We evaluated the effects of a 20-week chronic exposure of mice to a low dose of
      cypermethrin (CYP), atrazine (ATZ) and 17alpha-ethynyestradiol (EE2) on energy
      metabolism. Here, male mice were exposed to 50 MUg/kg BW/day CYP, 100 MUg/kg
      BW/day ATZ or 1 MUg/kg BW/day EE2 supplied in their drinking water for 20 weeks.
      During the exposure, mice were fed a high energy diet (HD). The bodyweights were
      not significantly affected by chronic exposure to EDCs, while the serum-free
      fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG)
      contents increased significantly in the ATZ- and CYP-HD groups. To determine the
      mechanism involved, we determined the expression levels of the genes in the
      glucose and fat metabolism pathways in the liver and adipose tissue. The results
      showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number
      of key genes involved in both the de novo FFA synthesis pathway and the transport
      of FFA from blood. The increased amount of FFA was partially consumed as energy
      through beta-oxidation in the mitochondria. Some of the FFA was used to
      synthesize TG in the liver by up-regulating primary genes, which resulted in
      increased TG levels and lipid accumulation. The results indicate that chronic
      exposure to EDCs has the potential to cause energy metabolic dysregulation and
      hepatotoxicity in mice.

PMID- 24440343
TI  - Heavy metal scavenger metallothionein attenuates ER stress-induced myocardial
      contractile anomalies: role of autophagy.
AB  - Endoplasmic reticulum (ER) stress increases the risk of cardiovascular morbidity
      and mortality although the underlying mechanism remains elusive. This study was
      designed to examine the impact of cardiac over-expression of metallothionein, a
      cysteine-rich heavy metal scavenger, on ER stress-induced changes in myocardial
      function and underlying mechanism involved with a focus on autophagy. Wild-type
      friendly virus B (FVB) and metallothionein transgenic mice were subjected to the
      ER stress inducer tunicamycin (1 mg/kg). Our results showed that ER stress led to
      compromised echocardiographic and cardiomyocyte contractile function,
      intracellular Ca(2+) mishandling. Tunicamycin promoted ER stress and oxidative
      stress, increased left ventricular end systolic and diastolic diameter, as well
      as suppressed fractional shortening and whole heart contractility, the effects of
      which were significantly attenuated or ablated by metallothionein. Levels of the
      autophagy markers such as phosphorylated ULK1, Atg5, Atg7, LC3B and the autophagy
      adaptor p62 were significantly upregulated. These ER stress-induced changes in
      myocardial function, autophagy and autophagy signaling were distinctly mitigated
      or alleviated by metallothionein. Inhibition of autophagy using 3-methyladenine
      in vitro reversed ER stress-induced cardiomyocyte contractile defects. Meanwhile,
      ER stress-induced cardiomyocyte dysfunction was attenuated by the antioxidant N
      acetylcysteine. Collectively, these findings suggested that metallothionein
      protects against ER stress-induced cardiac anomalies possibly through attenuation
      of cardiac autophagy.

PMID- 24440344
TI  - Assessment of drug delivery and anticancer potentials of nanoparticles-loaded
      siRNA targeting STAT3 in lung cancer, in vitro and in vivo.
AB  - Activation of signal transducer and activator of transcription3 (STAT3) is a
      hallmark of several types of cancer. Failure to inhibit STAT3 expression by
      injection of siRNA for STAT3 directly to Balb/c mice led us to adopt alternative
      means. We formulated nanoparticle-based encapsulation of siRNA (NsiRNA) with
      polyethylenimine (PEI) and poly(lactide-co-glycolide) (PLGA) and characterized
      them. The siRNA treated and NsiRNA-treated cells were subjected separately to
      different assay systems. We also checked if NsiRNA could cross the blood brain
      barrier (BBB). Cell viability reduced dramatically in A549 cells after NsiRNA
      administration (23.89% at 24 h), thereby implicating considerable silencing of
      STAT3 by NsiRNA, but not after siRNA administration. Compared to controls, a
      significant decrease in expression of IL-6 and the angiogenic factor (VEGF) and
      increase in Caspase 3 activity was observed with corresponding regression in
      tumor growth in mice treated with NsiRNA. NsiRNA induced apoptosis of cells and
      arrested cells at G1/G0 stage, both in vitro and in vivo. Apoptosis was also
      verified by Annexin-V-FITC/Propidium-iodide staining. NsiRNA could cross blood
      brain barrier. Overall results revealed PEI-PLGA to be a promising carrier for
      delivery of siRNA targeting STAT3 expression, which can be utilized as an
      effective strategy for cancer therapy.

PMID- 24440345
TI  - Regulation of corticosterone secretion is modified by PFOS exposure at different
      levels of the hypothalamic-pituitary-adrenal axis in adult male rats.
AB  - Perfluorooctane sulfonate (PFOS) is a fluorinated compound and a Persistent
      Organic Pollutant which can disrupt the endocrine system. This work was
      undertaken to evaluate the possible effects of PFOS exposure on the regulation of
      corticosterone secretion in adrenal and pituitary glands and at hypothalamic
      level in adult male rat, and to evaluate the possible morphological alterations
      induced by PFOS in this endocrine tissue. Adult male rats were orally treated
      with 0.5, 1.0, 3.0 and 6.0 mg of PFOS/kg/day for 28 days. Corticosterone,
      adrenocorticotropic hormone (ACTH) and corticotrophin-releasing hormone (CRH)
      secretion decreased in PFOS-treated rats. After PFOS exposure, relative
      expression of adrenocorticotropic hormone receptor (ACTHr) and
      proopiomelanocortin (POMC) genes was increased in adrenal and in pituitary
      glands, respectively; while relative expression of ACTHr and CRH genes decreased
      in hypothalamus with the doses of 0.5 and 1.0 mg/kg/day. PFOS treatment increased
      relative nitric oxide synthase 1 and 2 (NOS1 and NOS2) gene expression in the
      adrenal gland, and incremented superoxide dismutase activity. PFOS exposure
      induces a global inhibition of the hypothalamic-pituitary-adrenal (HPA) axis
      activity, and small morphological changes were observed in adrenal zona
      fasciculata cells.

PMID- 24440346
TI  - SOCS1 hypermethylation mediated by DNMT1 is associated with lipopolysaccharide
      induced inflammatory cytokines in macrophages.
AB  - Macrophages activation which releases the pro-inflammatory cytokines is an
      essential event in the process of inflammation. SOCS1 has been shown to act as a
      negative regulator of cytokine signals and plays a key role in the suppression of
      tissue injury and inflammatory diseases. DNA methylation mediated by specific DNA
      methyltransferases1 (DNMT1) which contributes to the epigenetic silencing of
      multiple genes. SOCS1 promoter hypermethylation is by far the best categorized
      epigenetic change in tumors. Our study with a view to investigate whether the
      loss of SOCS1 due to SOCS1 promoter methylation was involved in the course of
      inflammatory cytokines released from lipopolysaccharide (LPS)-stimulated
      macrophages. Here, we found that treatment of LPS-induced RAW264.7 macrophage
      cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC) reduced
      aberrant promoter hypermethylation of SOCS1 and prevented the loss of the
      expression of SOCS1 in macrophages which secret inflammatory cytokines. Knockdown
      of DNMT1 gene not only attenuated the SOCS1 gene promoter methylation but also up
      regulated the expression of SOCS1 in activated RAW264.7 cells. Furthermore,
      silencing of DNMT1 prevented the activation of JAK2/STAT3 pathway in LPS-induced
      RAW264.7 cells. These studies demonstrated that DNMT1-mediated SOCS1
      hypermethylation caused the loss of SOCS1 expression results in negative
      regulation of activation of the JAK2/STAT3 pathway, and enhanced the release of
      LPS-induced pro-inflammatory cytokines such as TNF-alpha and IL-6 in macrophages.

PMID- 24440347
TI  - Role of receptor interacting protein (RIP)1 on apoptosis-inducing factor-mediated
      necroptosis during acetaminophen-evoked acute liver failure in mice.
AB  - Acetaminophen (APAP) overdose induces apoptosis-inducing factor (AIF)-dependent
      necroptosis, but the mechanism remains obscure. The present study investigated
      the role of receptor interacting protein (RIP)1, a critical mediator of
      necroptosis, on AIF-dependent necroptosis during APAP-induced acute liver
      failure. Mice were intraperitoneally injected with APAP (300 mg/kg). As expected,
      hepatic RIP1 was activated as early as 1 h after APAP, which is earlier than APAP
      induced hepatic RIP3 upregulation. APAP-evoked RIP1 activation is associated with
      hepatic glutathione (GSH) depletion. Either pretreatment or post-treatment with
      Nec-1, a selective inhibitor of RIP1, significantly alleviated APAP-induced acute
      liver failure. Moreover, Nec-1 improved the survival and prevented APAP-induced
      necroptosis, as determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL)
      assay. Further analysis showed that Nec-1 significantly inhibited APAP-induced
      hepatic c-Jun N-terminal kinase (JNK) phosphorylation and mitochondrial Bax
      translocation. In addition, Nec-1 blocked APAP-induced translocation of AIF from
      the mitochondria to the nucleus. Of interest, no changes were induced by Nec-1 on
      hepatic CYP2E1 expression. In addition, Nec-1 had little effect on APAP-induced
      hepatic GSH depletion at early stage. Taken together, these results suggest that
      RIP1 is involved in APAP-induced necroptosis. Nec-1 is an effective antidote for
      APAP-induced acute liver failure.

PMID- 24440349
TI  - Experimental evidence for a 9-binding subsite of Bacillus licheniformis
      thermostable alpha-amylase.
AB  - The action pattern of Bacillus licheniformis thermostable alpha-amylase (BLA) was
      analyzed using a series of (14)C-labeled and non-labeled maltooligosaccharides
      from maltose (G2) to maltododecaose (G12). Maltononaose (G9) was the preferred
      substrate, and yielded the smallest Km=0.36 mM, the highest kcat=12.86 s(-1), and
      a kcat/Km value of 35.72 s(-1) mM(-1), producing maltotriose (G3) and
      maltohexaose (G6) as the major product pair. Maltooctaose (G8) was hydrolyzed
      into two pairs of products: G3 and maltopentaose (G5), and G2 and G6 with
      cleavage frequencies of 0.45 and 0.30, respectively. Therefore, we propose a
      model with nine subsites: six in the terminal non-reducing end-binding site and
      three at the reducing end-binding site in the binding region of BLA.

PMID- 24440348
TI  - Gap junction regulation by calmodulin.
AB  - Intracellular Ca(2+) activated calmodulin (CaM) inhibits gap junction channels in
      the low nanomolar to high micromolar range of [Ca(2+)]i. This regulation plays an
      essential role in numerous cellular processes that include hearing, lens
      transparency, and synchronized contractions of the heart. Previous studies have
      indicated that gap junction mediated cell-to-cell communication was inhibited by
      CaM antagonists. More recent evidence indicates a direct role of CaM in
      regulating several members of the connexin family. Since the intracellular loop
      and carboxyl termini of connexins are largely "invisible" in electron microscopy
      and X-ray crystallographic structures due to disorder in these domains, peptide
      models encompassing the putative CaM binding sites of several intracellular
      domains of connexins have been used to identify the Ca(2+)-dependent CaM binding
      sites of these proteins. This approach has been used to determine the CaM binding
      affinities of peptides derived from a number of different connexin-subfamilies. 

PMID- 24440350
TI  - Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads
      to MET accumulation by impairing the receptor downregulation.
AB  - The MET receptor tyrosine kinase is deregulated primarily via overexpression or
      point mutations in various human cancers and different strategies for MET
      inhibition are currently evaluated in clinical trials. We observed by Western
      blot analysis and by Flow cytometry that MET inhibition by different MET small
      molecule inhibitors surprisingly increases in a dose-dependent manner total MET
      levels in treated cells. Mechanistically, this inhibition-related MET
      accumulation was associated with reduced Tyr1003 phosphorylation and MET physical
      association with the CBL ubiquitin ligase with concomitant decrease in MET
      ubiquitination. These data may suggest careful consideration for design of anti
      MET clinical protocols. 

PMID- 24440351
TI  - C-reactive protein induces G2/M phase cell cycle arrest and apoptosis in
      monocytes through the upregulation of B-cell translocation gene 2 expression.
AB  - We hypothesized that C-reactive protein (CRP) may affect the cell cycle and
      induce apoptotic changes of monocytes. CRP (~25 MUg/ml) significantly increased
      expressions of B-cell translocation gene 2 (BTG2) mRNA and protein in human
      monocytes through pathways involving CD32/NADPH oxidase 2/p53, which eventually
      induced G2/M phase arrest and apoptotic cell death. Such pro-apoptotic effect of
      CRP was not found in thioglycollate-elicited intraperitoneal
      monocytes/macrophages harvested from BTG2-knockout male C57BL/6 mice (n=5).
      Within atheromatous plaques obtained from CRP-transgenic male LDLR(-/-) C57BL/6
      mice (n=5) and human coronary arteries, BTG2 co-localized with CRP, p53 and
      monocytes/macrophages. Therefore the pro-apoptotic pathway of CRP-CD32-Nox2-p53
      BTG2 may contribute to the retardation of the atherogenic process.

PMID- 24440352
TI  - MicroRNA-106a targets TIMP2 to regulate invasion and metastasis of gastric
      cancer.
AB  - Emerging evidence has shown that microRNA plays an important role in tumor
      development and progression. Here, we report that miR-106a is frequently up
      regulated in gastric cancer tissues and positively correlates with metastasis.
      Restrained expression of miR-106a in gastric cancer cells significantly reduces
      their capacity of proliferation, migration and invasion. In tissue sections, the
      positive signal of miR-106a localized in metastasis-associated regions confirmed
      this result. Moreover, we show that TIMP2 is a direct downstream target for miR
      106a and knockdown of TIMP2 strengthens the beneficial effects of miR-106a. Our
      study adds miR-106a to the complex mechanisms of tumor metastasis. 

PMID- 24440353
TI  - New insights into the substrate specificities of proton-coupled oligopeptide
      transporters from E. coli by a pH sensitive assay.
AB  - Proton-coupled oligopeptide transporters (POTs) are secondary active transporters
      that facilitate di- and tripeptide uptake by coupling it to an inward directed
      proton electrochemical gradient. Here the substrate specificities of Escherichia
      coli POTs YdgR, YhiP and YjdL were investigated by means of a label free
      transport assay using the hydrophilic pH sensitive dye pyranine and POT
      overexpressing E. coli cells. The results confirm and extend the functional
      knowledge on E. coli POTs. In contrast to previous assumptions, alanine and
      trialanine appears to be substrates of YjdL, albeit poor compared to dipeptides.
      Similarly tetraalanine apparently is a substrate of both YdgR and YhiP. 

PMID- 24440354
TI  - A simple method for the determination of reduction potentials in heme proteins.
AB  - We describe a simple method for the determination of heme protein reduction
      potentials. We use the method to determine the reduction potentials for the PAS-A
      domains of the regulatory heme proteins human NPAS2 (Em=-115 mV +/- 2 mV, pH 7.0)
      and human CLOCK (Em=-111 mV +/- 2 mV, pH 7.0). We suggest that the method can be
      easily and routinely applied to the determination of reduction potentials across
      the family of heme proteins.

PMID- 24440355
TI  - Contribution of small heat shock proteins to muscle development and function.
AB  - Investigations undertaken over the past years have led scientists to introduce
      the concept of protein quality control (PQC) systems, which are responsible for
      polypeptide processing. The PQC system monitors proteostasis and involves
      activity of different chaperones such as small heat shock proteins (sHSPs). These
      proteins act during normal conditions as housekeeping proteins regulating
      cellular processes, and during stress conditions. They also mediate the removal
      of toxic misfolded polypeptides and thereby prevent development of pathogenic
      states. It is postulated that sHSPs are involved in muscle development. They
      could act via modulation of myogenesis or by maintenance of the structural
      integrity of signaling complexes. Moreover, mutations in genes coding for sHSPs
      lead to pathological states affecting muscular tissue functioning. This review
      focuses on the question how sHSPs, still relatively poorly understood proteins,
      contribute to the development and function of three types of muscle tissue:
      skeletal, cardiac and smooth. 

PMID- 24440356
TI  - Proteasome involvement in a complex cascade mediating SigT degradation during
      differentiation of Streptomyces coelicolor.
AB  - In Streptomyces coelicolor, the ECF sigma factor SigT negatively regulates cell
      differentiation, and is degraded by ClpP protease in a dual positive feedback
      manner. Here we further report that the proteasome is required for degradation of
      SigT, but not for degradation of its anti-sigma factor RstA, and RstA can protect
      SigT from degradation independent of the proteasome. Meanwhile, deletion of the
      proteasome showed reduced production of secondary metabolites, and the
      fermentation medium from wild type could promote SigT degradation. Furthermore,
      overexpression of redD or actII-orf4 in the proteasome-deficiency mutant resulted
      in SigT degradation and over-production of both undecylprodigiosin and
      actinorhodin. Therefore the proteasome is required for SigT degradation by
      affecting the production of secondary metabolites during cell differentiation. 

PMID- 24440357
TI  - Reliability of the Performance of Upper Limb assessment in Duchenne muscular
      dystrophy.
AB  - The Performance of Upper Limb was specifically designed to assess upper limb
      function in Duchenne muscular dystrophy. The aim of this study was to assess (1)
      a cohort of typically developing children from the age of 3years onwards in order
      to identify the age when the activities assessed in the individual items are
      consistently achieved, and (2) a cohort of 322 Duchenne children and young adults
      to establish the range of findings at different ages. We collected normative data
      for the scale validation on 277 typically developing subjects from 3 to 25years
      old. A full score was consistently achieved by the age of 5years. In the Duchenne
      cohort there was early involvement of the proximal muscles and a proximal to
      distal progressive involvement. The scale was capable of measuring small distal
      movements, related to activities of daily living, even in the oldest and weakest
      patients. Our data suggest that the assessment can be reliably used in both
      ambulant and non ambulant Duchenne patients in a multicentric setting and could
      therefore be considered as an outcome measure for future trials. 

PMID- 24440359
TI  - Pathophysiology of staphylococci in the post-genomic era.

PMID- 24440358
TI  - Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are
      linked to heme consumption in a bacteremic strain of Acinetobacter baumannii.
AB  - Bacteremia caused by Acinetobacter baumannii is a highly lethal complication of
      hospital-acquired pneumonia. In the present study, we investigated the serum
      resistance, gallium nitrate tolerance and heme consumption of A. baumannii strain
      LAC-4 which was recently reported to display high virulence in a mouse pneumonia
      model with extrapulmonary dissemination leading to fatal bacteremia. This strain
      showed enhanced growth in mouse and fetal bovine serum that was independent of
      complement and was not observed with regular growth media. The LAC-4 strain was
      found to possess a high tolerance to gallium nitrate (GaN), whereas serum
      synergized with GaN in inhibiting A. baumannii strain ATCC 17978. We found that
      LAC-4 contains a heme oxygenase gene and expresses a highly efficient heme
      consumption system. This system can be fully blocked in vitro and in vivo by
      gallium protoporphyrin IX (GaPPIX). Inhibition of heme consumption by GaPPIX
      completely abrogated the growth advantage of LAC-4 in serum as well as its
      tolerance to GaN. More importantly, GaPPIX treatment of mice intranasally
      infected with LAC-4 prevented extrapulmonary dissemination and death. Thus, we
      propose that heme provides an additional source of iron for LAC-4 to bypass iron
      restriction caused by serum transferrin, lactoferrin or free gallium salts. Heme
      consumption systems in A. baumannii may constitute major virulence factors for
      lethal bacteremic isolates. 

PMID- 24440360
TI  - Wiskott-Aldrich Syndrome causing mutation, Pro373Ser restricts conformational
      changes essential for WASP activity in T-cells.
AB  - Wiskott-Aldrich Syndrome (WAS) is caused by mutations in Wiskott-Aldrich Syndrome
      Protein (WASP) and majority of the mutations are found in the WASP Homology 1
      (WH1) domain which mediates interaction with WIP (WASP Interacting Protein), a
      WASP chaperone. Two point mutations together in the proline rich region (PRR)
      domain of WASP (S339Y/P373S) have been reported to cause WAS however the
      molecular defect has not been characterized. Expression of these mutants
      separately (WASPR(S339Y), WASPR(P373S)) or together (WASPR(SP/YS)) did not rescue
      the chemotaxis defect or membrane projection defect of Jurkat(WKD) T-cells (WASP
      knockdown). This is not due to the inability of WASP-PRR mutants to form
      functional WASP-WIP complex in growth rescue experiments in las17Delta yeast
      strain. Expression of WASPR(S339Y) but not WASPR(P373S) or WASPR(SP/YS) rescued
      the IL-2 expression defect of Jurkat(WKD) T-cells, suggesting that Pro373Ser
      mutation alone is sufficient to inhibit WASP functions in T-cell activation. The
      diffused localization of WASP-PRR mutants in activated Jurkat T-cells suggests
      that Ser339 and Pro373 are critical for WASP localization. WASP-PRR mutations
      either together or individually did not abolish interaction of WASP with sixteen
      WASP binding proteins including Hck, however they caused reduction in Hck
      mediated tyrosine phosphorylation of WASP which is critical for WASP activity.
      The auto-inhibitory conformation of WASP(P373S) mutant was not relieved by the
      binding of Toca-1 or Nck1. Thus, our results suggest that Pro373Ser mutation
      reduces Tyr291 phosphorylation and prevents conformational changes required for
      WASP activity in chemotaxis and T-cell activation. Thus Pro3373Ser is probably
      responsible for all the defects associated with WAS in the patients.

PMID- 24440361
TI  - The combination of Bifidobacterium breve with non-digestible oligosaccharides
      suppresses airway inflammation in a murine model for chronic asthma.
AB  - Over the last decade, there has been a growing interest in the use of
      interventions that target the intestinal microbiota as a treatment approach for
      asthma. This study is aimed at exploring the therapeutic effects of long-term
      treatment with a combination of Bifidobacterium breve with non-digestible
      oligosaccharides on airway inflammation and remodeling. A murine ovalbumin
      induced chronic asthma model was used. Pulmonary airway inflammation; mRNA
      expression of pattern recognition receptors, Th-specific cytokines and
      transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in
      vitro T cell activation; mast cell degranulation; and airway remodeling were
      examined. The combination of B. breve with non-digestible oligosaccharides
      suppressed pulmonary airway inflammation; reduced T cell activation and mast cell
      degranulation; modulated expression of pattern recognition receptors, cytokines
      and transcription factors; and reduced airway remodeling. The treatment induced
      regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription
      in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T
      cells. This specific combination of beneficial bacteria with non-digestible
      oligosaccharides has strong anti-inflammatory properties, possibly via the
      induction of a regulatory T cell response, resulting in reduced airway remodeling
      and, therefore, may be beneficial in the treatment of chronic inflammation in
      allergic asthma.

PMID- 24440362
TI  - Posterolateral hip muscle strengthening versus quadriceps strengthening for
      patellofemoral pain: a comparative control trial.
AB  - OBJECTIVE: To compare the efficacy of posterolateral hip muscle strengthening
      versus quadriceps strengthening in reducing pain and improving health status in
      persons with patellofemoral pain (PFP). DESIGN: Comparative control trial.
      SETTING: Rehabilitation facility. PARTICIPANTS: Persons with a diagnosis of PFP
      (N=36; 18 men, 18 women). INTERVENTIONS: Patients were alternately assigned to a
      posterolateral hip muscle strengthening group (9 men and 9 women) or a quadriceps
      strengthening group (9 men and 9 women). The posterolateral hip muscle
      strengthening group performed hip abductor and external rotator strengthening
      exercises, whereas the quadriceps strengthening group performed quadriceps
      strengthening exercises (3 times a week for 8wk). MAIN OUTCOME MEASURES: Pain
      (visual analog scale [VAS]) and health status (Western Ontario McMaster
      Universities Osteoarthritis Index [WOMAC]) were assessed at baseline,
      postintervention, and 6-month follow-up. RESULTS: Significant improvements in VAS
      and WOMAC scores were observed in both groups from baseline to postintervention
      and baseline to 6-month follow-up (P<.001). Improvements in VAS and WOMAC scores
      in the posterolateral hip exercise group were superior to those in the quadriceps
      exercise group postintervention and at 6-month follow-up (P<.05). CONCLUSIONS:
      Although both intervention programs resulted in decreased pain and improved
      function in persons with PFP, outcomes in the posterolateral hip exercise group
      were superior to the quadriceps exercise group. The superior outcomes obtained in
      the posterolateral hip exercise group were maintained 6 months postintervention.

PMID- 24440363
TI  - Feasibility of computerized adaptive testing for collection of patient-reported
      outcomes after inpatient rehabilitation.
AB  - OBJECTIVE: To evaluate the feasibility of computer adaptive testing (CAT) using
      an Internet or telephone interface to collect patient-reported outcomes after
      inpatient rehabilitation and to examine patient characteristics associated with
      completion of the CAT-administered measure and mode of administration. DESIGN:
      Prospective cohort study of patients contacted approximately 4 weeks after
      discharge from inpatient rehabilitation. Patients selected an Internet or
      telephone interface. SETTING: Rehabilitation hospital. PARTICIPANTS: Patients
      (N=674) with diagnoses of neurologic, orthopedic, or medically complex
      conditions. INTERVENTIONS: None. MAIN OUTCOME MEASURE: CAT version of the
      Community Participation Indicators (CAT-CPI). RESULTS: From an eligible pool of
      3221 patients, 674 (21%) agreed to complete the CAT-CPI. Patients who agreed to
      complete the CAT-CPI were younger and reported slightly higher satisfaction with
      overall care than those who did not participate. Among these patients, 231 (34%)
      actually completed the CAT-CPI; 141 (61%) selected telephone administration, and
      90 (39%) selected Internet administration. Decreased odds of completing the CAT
      CPI were associated with black and other race; stroke, brain injury, or
      orthopedic and other impairments; and being a Medicaid beneficiary, whereas
      increased odds of completing the CAT-CPI were associated with longer length of
      stay and higher discharge FIM cognition measure. Decreased odds of choosing
      Internet administration were associated with younger age, retirement status, and
      being a woman, whereas increased odds of choosing Internet administration were
      associated with higher discharge FIM motor measure. CONCLUSIONS: CAT
      administration by Internet and telephone has limited feasibility for collecting
      postrehabilitation outcomes for most rehabilitation patients, but it is feasible
      for a subset of patients. Providing alternative ways of answering questions helps
      assure that a larger proportion of patients will respond.

PMID- 24440365
TI  - Robotic resistance/assistance training improves locomotor function in individuals
      poststroke: a randomized controlled study.
AB  - OBJECTIVE: To determine whether providing a controlled resistance versus
      assistance to the paretic leg at the ankle during treadmill training will improve
      walking function in individuals poststroke. DESIGN: Repeated assessment of the
      same patients with parallel design and randomized controlled study between 2
      groups. SETTING: Research units of rehabilitation hospitals. PARTICIPANTS:
      Patients (N=30) with chronic stroke. INTERVENTION: Subjects were stratified based
      on self-selected walking speed and were randomly assigned to the resistance or
      assistance training group. For the resistance group, a controlled resistance load
      was applied to the paretic leg at the ankle to resist leg swing during treadmill
      walking. For the assistance group, a load that assists swing was applied. MAIN
      OUTCOME MEASURES: Primary outcome measures were walking speed and 6-minute
      walking distance. Secondary measures included clinical assessments of balance,
      muscle tone, and quality of life. Outcome measures were evaluated before and
      after 6 weeks of training and at 8 weeks' follow-up, and compared within group
      and between the 2 groups. RESULTS: After 6 weeks of robotic training, walking
      speed significantly increased for both groups, with no significant differences in
      walking speed gains observed between the 2 groups. In addition, 6-minute walking
      distance and balance significantly improved for the assistance group but not for
      the resistance group. CONCLUSIONS: Applying a controlled resistance or an
      assistance load to the paretic leg during treadmill training may induce
      improvements in walking speed in individuals poststroke. Resistance training was
      not superior to assistance training in improving locomotor function in
      individuals poststroke.

PMID- 24440366
TI  - Pre- and postsynaptic type-1 cannabinoid receptors control the alterations of
      glutamate transmission in experimental autoimmune encephalomyelitis.
AB  - Type-1 cannabinoid receptors (CB1R) are important regulators of the
      neurodegenerative damage in multiple sclerosis (MS) and in experimental
      autoimmune encephalomyelitis (EAE). In GABAergic striatal neurons, CB1R
      stimulation exerts protective effects by limiting inflammation-induced
      potentiation of glutamate-mediated spontaneous excitatory postsynaptic currents
      (sEPSCs). Here we show that CB1R located on GABAergic or on glutamatergic neurons
      are differentially involved in the pre- and postsynaptic alterations of sEPSCs
      caused by EAE in the striatum. After induction of EAE, mice selectively lacking
      CB1R on GABAergic neurons (GABA-CB1R-KO) showed exacerbated alterations of sEPSC
      duration in GABAergic medium spiny neurons (MSN). On the other hand, EAE-induced
      alterations of corticostriatal sEPSC frequency were exacerbated only in mice
      lacking CB1R on glutamatergic neurons (Glu-CB1R-KO), indicating that this subset
      of receptors controls the effects of inflammation on glutamate release. While EAE
      severity was enhanced in whole CB1R-KO mice, GABA-CB1R-KO and Glu-CB1R-KO mice
      had similar motor deficits as the respective wild-type (WT) counterparts. Our
      results provide further evidence that CB1R are involved in EAE pathophysiology,
      and suggest that both pre- and postsynaptic alterations of glutamate transmission
      are important to drive excitotoxic neurodegeneration typical of this disorder. 

PMID- 24440364
TI  - Nonparetic arm force does not overinhibit the paretic arm in chronic poststroke
      hemiparesis.
AB  - OBJECTIVE: To determine whether nonparetic arm force overinhibits the paretic arm
      in patients with chronic unilateral poststroke hemiparesis. DESIGN: Case-control
      neurophysiological and behavioral study of patients with chronic stroke. SETTING:
      Research institution. PARTICIPANTS: Eighty-six referred patients were screened to
      enroll 9 participants (N=9) with a >6 month history of 1 unilateral ischemic
      infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of
      wrist flexion torque and without contraindication to transcranial magnetic
      stimulation. Eight age- and handedness-matched healthy volunteers without
      neurologic diagnosis were studied for comparison. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURE: Change in interhemispheric inhibition targeting the
      ipsilesional primary motor cortex (M1) during nonparetic arm force. We
      hypothesized that interhemispheric inhibition would increase more in healthy
      controls than in patients with hemiparesis. RESULTS: Healthy age-matched controls
      had significantly greater increases in inhibition from their active to resting M1
      than patients with stroke from their active contralesional to resting
      ipsilesional M1 in the same scenario (20%+/-7% vs -1%+/-4%, F1,12=6.61, P=.025).
      Patients with greater increases in contralesional to ipsilesional inhibition were
      better performers on the 9-hole peg test of paretic arm function. CONCLUSIONS:
      Our findings reveal that producing force with the nonparetic arm does not
      necessarily overinhibit the paretic arm. Though our study is limited in
      generalizability by the small sample size, we found that greater active
      contralesional to resting ipsilesional M1 inhibition was related with better
      recovery in this subset of patients with chronic poststroke.

PMID- 24440367
TI  - Neuronal over-expression of ACE2 protects brain from ischemia-induced damage.
AB  - Angiotensin (Ang) II exaggerates cerebral injury in ischemic damage. Angiotensin
      converting enzyme type 2 (ACE2) converts Ang II into Ang (1-7) and thus, may
      protect against the effects of Ang II. We hypothesized that neuronal ACE2 over
      expression decreases ischemic stroke in mice with Ang II overproduction. Human
      renin and angiotensinogen double transgenic (RA) mice and RA mice with neuronal
      over-expression of ACE2 (SARA) were used for the study. The mean arterial
      pressure (MAP) was calculated from telemetry-recorded blood pressure (BP). SARA
      mice were infused peripherally with Norepinephrine to "clamp" the BP, or
      intracerebroventricularly-infused with a Mas receptor antagonist (A-779). Middle
      cerebral artery occlusion (MCAO) surgery was performed to induce permanent focal
      ischemic stroke. Cerebral blood flow (CBF) and neurological function were
      determined. Two days after surgery, brain samples were collected for various
      analyses. Results showed: 1) When compared to chronically hypertensive RA mice,
      SARA mice had lower basal MAP, less MCAO-induced infarct volume, and increased
      CBF, neurological function and cerebral microvascular density in the peri-infarct
      area; 2) These changes in SARA mice were not altered after MAP "clamping", but
      partially reversed by brain infusion of A-779; 3) Ang (1-7)/Ang II ratio,
      angiogenic factors, endothelial nitric oxide synthase (eNOS) expression and
      nitric oxide production were increased, whereas, NADPH oxidase subunits and
      reactive oxygen species were decreased in the brain of SARA mice. ACE2 protects
      brain from ischemic injury via the regulation of NADPH oxidase/eNOS pathways by
      changing Ang (1-7)/Ang II ratio, independently of MAP changes. 

PMID- 24440369
TI  - Psychostimulants and brain dysfunction: a review of the relevant neurotoxic
      effects.
AB  - Psychostimulants abuse is a major public concern because is associated with
      serious health complications, including devastating consequences on the central
      nervous system (CNS). The neurotoxic effects of these drugs have been extensively
      studied. Nevertheless, numerous questions and uncertainties remain in our
      understanding of these toxic events. Thus, the purpose of the present manuscript
      is to review cellular and molecular mechanisms that might be responsible for
      brain dysfunction induced by psychostimulants. Topics reviewed include some
      classical aspects of neurotoxicity, such as monoaminergic system and
      mitochondrial dysfunction, oxidative stress, excitotoxicity and hyperthermia.
      Moreover, recent literature has suggested new phenomena regarding the toxic
      effects of psychostimulants. Thus, we also reviewed the impact of these drugs on
      neuroinflammatory response, blood-brain barrier (BBB) function and neurogenesis.
      Assessing the relative importance of these mechanisms on psychostimulants-induced
      brain dysfunction presents an exciting challenge for future research efforts.
      This article is part of the Special Issue entitled 'CNS Stimulants'. 

PMID- 24440370
TI  - The perceptual logic of smell.
AB  - Mammals have ~1000 different olfactory receptor subtypes, each responding to a
      number of different odorants, and each odorant activating a number of different
      receptor subtypes. These molecular and anatomical underpinnings of olfaction
      imply a perceptual structure of very high dimensionality that relies on
      combinatorial coding. In contrast to this expectation, the study of olfactory
      perception reveals a structure of much lower dimensionality. Moreover, a low
      dimensionality approach to olfaction enabled derivation of perception-based
      structural metrics for smell. These metrics provided meaningful predictions of
      odorant-induced neural activity and perception from odorant structure alone.
      Based on this low functional dimensionality, we speculate that olfaction likely
      does not functionally rely on 1000 different receptor subtypes, and their
      persistence in evolution may imply that they have additional roles in non
      olfactory functions such as in guidance of embryogenesis and development.

PMID- 24440368
TI  - Probing NMDA receptor GluN2A and GluN2B subunit expression and distribution in
      cortical neurons.
AB  - The spatial distribution of N-methyl-d-aspartate receptor (NMDAR) subunits in
      layer 5 (L5) neurons of the medial prefrontal cortex (mPFC) is important for
      integrating input-output signals involved in cognitive functions and motor
      behavior. In this study, focal laser scanning photostimulation of caged
      glutamate, slice electrophysiology, and small peptide pharmacology, were used to
      map the distribution of functional GluN2A and GluN2B subunits of the NMDAR from
      L5 neurons of wild-type (WT) and GluN2A(-/-) mice. Focal uncaging of glutamate
      evoked spatially-restricted glutamatergic responses on various dendritic
      locations of pyramidal neurons in the mPFC. Analyses of the spatial arrangements
      of the GluN2A and GluN2B subunits were performed by comparing inhibition of
      glutamatergic responses in the presence of the GluN2A-selective pharmacological
      antagonist, NVP-AAM077 (NVP), and the GluN2B-selective peptidic antagonist,
      conantokin-G (con-G). We found that apical and basal expression and distribution
      of GluN2A and GluN2B were similar in L5 mPFC neurons of WT mice. However, the
      inhibition of glutamatergic responses by NVP in brain slices of GluN2A(-/-) mice
      were dramatically decreased, while con-G inhibition remained similar to that
      observed in WT brain slices. The data obtained show that expression and spatial
      arrangement of GluN2B subunits is independent of GluN2A in L5 neurons of the
      mPFC. These findings have important ramifications for NMDAR organization and
      function in L5 pyramidal neurons of the mPFC, and show that specific populations
      of NMDARs can be antagonized, while sparing other subgroups of NMDARs, thus
      preserving selective NMDAR functions, an important therapeutic advantage. 

PMID- 24440371
TI  - Acidified nitrite: a host defence against colonization with C. difficile spores?
AB  - Proton pump inhibitor (PPI) use increases the risk of Clostridium difficile
      infection (CDI) despite C. difficile spores being acid resistant. Swallowed
      saliva contains nitrite which reacts with gastric acid, producing bactericidal
      nitrogen oxides. With 5mM nitrite at pH 2 (reflecting normal gastric conditions)
      all C. difficile spores were killed within 15 min. No reduction in count was seen
      with the same nitrite concentration at pH 5, representing gastric conditions in
      patients taking PPIs, even after 60 min. Reduced gastric acidification of
      salivary nitrite may explain the increased risk of CDI in patients taking PPIs.

PMID- 24440372
TI  - Abnormal functional connectivity of the medial cortex in euthymic bipolar II
      disorder.
AB  - This project utilized functional MRI (fMRI) and a motor activation paradigm to
      investigate neural circuitry in euthymic bipolar II disorder. We hypothesized
      that circuitry involving the cortical midline structures (CMS) would demonstrate
      abnormal functional connectivity. Nineteen subjects with recurrent bipolar
      disorder and 18 controls were studied using fMRI and a motor activation paradigm.
      We used functional connectivity analyses to identify circuits with aberrant
      connectivity. We found increased functional connectivity among bipolar subjects
      compared to healthy controls in two CMS circuits. One circuit included the medial
      aspect of the left superior frontal gyrus and the dorsolateral region of the left
      superior frontal gyrus. The other included the medial aspect of the right
      superior frontal gyrus, the dorsolateral region of the left superior frontal
      gyrus and the right medial frontal gyrus and surrounding region. Our results
      indicate that CMS circuit dysfunction persists in the euthymic state and thus may
      represent trait pathology. Future studies should address whether these circuits
      contribute to relapse of illness. Our results also suggest the possibility that
      aberrations of superior frontal circuitry may impact default mode network and
      cognitive processes. 

PMID- 24440373
TI  - Abnormal topological organization in white matter structural networks revealed by
      diffusion tensor tractography in unmedicated patients with obsessive-compulsive
      disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder
      defined by recurrent thoughts, intrusive and distressing impulses, or images and
      ritualistic behaviors. Although focal diverse regional abnormalities white matter
      integrity in specific brain regions have been widely studied in populations with
      OCD, alterations in the structural connectivities among them remain poorly
      understood. OBJECTIVE: The aim was to investigate the abnormalities in the
      topological efficiency of the white matter networks and the correlation between
      the network metrics and Yale-Brown Obsessive-Compulsive Scale scores in
      unmedicated OCD patients, using diffusion tensor tractography and graph
      theoretical approaches. METHODS: This study used diffusion tensor imaging and
      deterministic tractography to map the white matter structural networks in 26 OCD
      patients and 39 age- and gender-matched healthy controls; and then applied graph
      theoretical methods to investigate abnormalities in the global and regional
      properties of the white matter network in these patients. RESULTS: The patients
      and control participants both showed small-world organization of the white matter
      networks. However, the OCD patients exhibited significant abnormal global
      topology, including decreases in global efficiency (t = -2.32, p = 0.02) and
      increases in shortest path length, Lp (t = 2.30, p = 0.02), the normalized
      weighted shortest path length, lambda (t = 2.08, p=0.04), and the normalized
      clustering coefficient, gamma (t = 2.26, p = 0.03), of their white matter
      structural networks compared with healthy controls. Further, the OCD patients
      showed a reduction in nodal efficiency predominately in the frontal regions, the
      parietal regions and caudate nucleus. The normalized weighted shortest path
      length of the network metrics was significantly negatively correlated with
      obsessive subscale of the Yale-Brown Obsessive-Compulsive Scale (r = -0.57, p =
      0.0058). CONCLUSIONS: These findings demonstrate the abnormal topological
      efficiency in the white matter networks in OCD patients.

PMID- 24440374
TI  - Zebra-borne equine herpesvirus type 1 (EHV-1) infection in non-African captive
      mammals.
AB  - Equine herpesvirus type 1 (EHV-1) was detected in an Indian rhinoceros
      (Rhinoceros unicornis), which was euthanized because of severe neurological
      disease. Encephalitis was suspected and EHV-1 DNA was detected in brain, lung,
      and spleen tissues. The viral IR6 protein was detected in lung tissues by Western
      blot analysis. Phylogenetic analyses of EHV-1 sequences amplified from various
      tissues was nearly identical to one recently described that resulted in both non
      fatal and fatal encephalitis in polar bears. This represents transmission of EHV
      1 to a species that is not naturally sympatric with the natural host of the virus
      and broadens the host range to Asian non-equid perissodactyls. 

PMID- 24440375
TI  - Lyssavirus distribution in naturally infected bats from Germany.
AB  - In Germany, to date three different lyssavirus species are responsible for bat
      rabies in indigenous bats: the European Bat Lyssaviruses type 1 and 2 (EBLV-1,
      EBLV-2) and the Bokeloh Bat Lyssavirus (BBLV) for which Eptesicus serotinus,
      Myotis daubentonii and Myotis nattereri, respectively, are primary hosts.
      Lyssavirus maintenance, evolution, and epidemiology are still insufficiently
      explored. Moreover, the small number of bats infected, the nocturnal habits of
      bats and the limited experimental data still hamper attempts to understand the
      distribution, prevalence, and in particular transmission of the virus. In an
      experimental study in E. serotinus a heterogeneous dissemination of EBLV-1 in
      tissues was detected. However, it is not clear whether the EBLV-1 distribution is
      similar in naturally infected animals. In an attempt to further analyze virus
      dissemination and viral loads within naturally infected hosts we investigated
      tissues of 57 EBLV-1 positive individuals of E. serotinus from Germany by RT-qPCR
      and compared the results with those obtained experimentally. Additionally, tissue
      samples were investigated with immunohistochemistry to detect lyssavirus antigen
      in defined structures. While in individual animals virus RNA was present only in
      the brain, in the majority of E. serotinus viral RNA was found in various tissues
      with highest relative viral loads detected in the brain. Interestingly, viral
      antigen was confirmed in various tissues in the tongue including deep
      intralingual glands, nerves, muscle cells and lingual papillae. So, the tongue
      appears to be a prominent site for virus replication and possibly shedding. 

PMID- 24440377
TI  - Membrane damaging activity of a maslinic acid analog.
AB  - Close inspection of human ovarian cancer cells A2780 in the course of an
      antitumor screening using maslinic acid analogs revealed for one of the
      compounds, 4-oxa-4-phenyl-butyl 2,3-dihydroxy-olean-12-en-28-oate (1), an unusual
      behavior. During the incubation of the cells with 1, at the perimeter of the
      cells or close by crystals were formed consisting of cholesterol and excess 1.
      Compound 1 was incorporated into the cell's membrane followed by an extrusion of
      cholesterol from the lipid rafts. As a consequence of the alterations of the cell
      membrane, a volume decrease was initiated that triggered apoptosis; this extends
      previous models on apoptosis initiating mechanisms. 

PMID- 24440376
TI  - The phenolic metabolites of the anti-HIV drug efavirenz: evidence for distinct
      reactivities upon oxidation with Fremy's salt.
AB  - Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor administered
      as first line treatment against HIV-1. The major drawbacks of EFV therapy are
      neurotoxicity and hepatotoxicity, which may result from bioactivation to reactive
      metabolites capable of reacting with bionucleophiles. We investigated the in
      vitro oxidation of the phenolic EFV metabolites, 7-hydroxy-efavirenz (7-OH-EFV)
      and 8-hydroxy-efavirenz (8-OH-EFV), with Fremy's salt. A quinoline derivative, 6
      chloro-2-cyclopropyl-4-(trifluoromethyl)quinolin-7-ol, presumably stemming from a
      radical rearrangement, was selectively obtained from 7-OH-EFV in 10% yield. In
      contrast, when subjected to the same oxidation conditions, 8-OH-EFV was
      considerably more prone to oxidative degradation and yielded multiple products.
      Among these, a quinone-imine derivative was tentatively identified upon LC-ESI
      MS/MS analysis of the reaction mixture. These observations demonstrate a
      remarkable difference in the reactivities of the two phenolic EFV metabolites
      under oxidative conditions. Moreover, taking into consideration the toxicological
      significance of quinone-imine derivatives, these findings may explain earlier
      reports that 8-OH-EFV is a more potent toxicant than 7-OH-EFV in model test
      systems. 

PMID- 24440378
TI  - N-(3-Arylaminopyridin-4-yl)alkanesulfonamides as pyridine analogs of nimesulide:
      cyclooxygenases inhibition, anti-inflammatory studies and insight on metabolism.
AB  - Nimesulide, a COX-2 preferential inhibitor with a favorable gastric and
      cardiovascular safety profile, was responsible for some cases of acute liver
      failure attributed to the nitrobenzene ring. A series of analogs of nimesulide
      resulting from isosteric replacement of the nitrobenzene ring by the pyridine
      nucleus, was synthesized and their ability to inhibit both cyclooxygenases (COXs)
      isoforms was evaluated in vitro using a human whole blood model. Compounds 19c,
      23b and 23c displayed an important inhibitory activity associated to a COX-2/COX
      1 selectivity ratio similar to or higher than that of celecoxib. The anti
      inflammatory activity and the ability of several compounds to decrease leukocyte
      infiltration were further evaluated in vivo in a model of a lambda carrageenan
      induced pleurisy. Plasma assays were performed on blood samples collected from
      rats and allowed us to identify the 4-position of the phenyl ring as a major
      metabolism site explaining the occasionally observed lack of correlation between
      in vitro and in vivo results.

PMID- 24440380
TI  - Arylnitroalkenes as scavengers of macrophage-generated oxidants.
AB  - Oxygen and nitrogen derived molecules mediated oxidation and nitration have been
      involved in several pathological conditions. Conversely, nitric oxide and
      hydrogen peroxide are important signalization intermediates, whose concentrations
      are tightly regulated by specialized enzyme repertoires and should remain
      undisturbed by the addition of exogenous antioxidant molecules, as already
      demonstrated by intervention studies with antioxidant vitamins. Our goal was to
      develop specific antioxidants able to scavenge peroxynitrite anion, as well the
      radicals derived from the homolytic decomposition of its conjugated acid,
      nitrogen dioxide and hydroxyl radical. Fourteen substituted nitroalkenes, seven 4
      substituted 1-(2-nitro-1Z-ethenyl)benzene, and seven 4-substituted (2-nitro-1Z
      propenyl)benzene, with different stereochemical and electronic characteristics
      were synthesized and tested. Compounds with the electron donor group N,N
      dimethylamino showed the highest reaction rates against peroxynitrite, and also
      reacted with its homolytic decomposition products, OH and NO2. While 1,1
      dimethylamino-4-(2-nitro-1Z-ethenyl)benzene came up as a lead for future
      developments without the risk of interfering with signalization pathways, since
      it was highly specific for peroxynitrite and peroxynitrite derived radicals, its
      methylated analogous 1,1-dimethylamino-4-(2-nitro-1Z-propenyl)benzene was less
      specific and also reacted with NO and O2(-), the biological precursor of H2O2.

PMID- 24440379
TI  - Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles
      as voltage-gated sodium channel modulators.
AB  - Voltage-gated sodium channels play an integral part in neurotransmission and
      their dysfunction is frequently a cause of various neurological disorders. On the
      basis of the structure of marine alkaloid clathrodin, twenty eight new analogs
      were designed, synthesized and tested for their ability to block human NaV1.3,
      NaV1.4 and NaV1.7 channels, as well as for their selectivity against human
      cardiac isoform NaV1.5, using automated patch clamp electrophysiological assay.
      Several compounds exhibited promising activities on different NaV channel
      isoforms in the medium micromolar range and some of the compounds showed also
      moderate isoform selectivities. The most promising results were obtained for the
      NaV1.3 channel, for which four compounds were found to possess IC50 values lower
      than 15 MUM. All of the active compounds bind to the open-inactivated states of
      the channels and therefore act as state-dependent modulators. The obtained
      results validate the approach of using natural products driven chemistry for drug
      discovery starting points and represent a good foundation for future design of
      selective NaV modulators.

PMID- 24440381
TI  - Noninvasive electrocardiographic mapping to guide ablation of outflow tract
      ventricular arrhythmias.
AB  - BACKGROUND: Localizing the origin of outflow tract ventricular tachycardias
      (OTVT) is hindered by lack of accuracy of electrocardiographic (ECG) algorithms
      and infrequent spontaneous premature ventricular complexes (PVCs) during
      electrophysiological studies. OBJECTIVES: To prospectively assess the performance
      of noninvasive electrocardiographic mapping (ECM) in the pre-/periprocedural
      localization of OTVT origin to guide ablation and to compare the accuracy of ECM
      with that of published ECG algorithms. METHODS: Patients with symptomatic
      OTVT/PVCs undergoing clinically indicated ablation were recruited. The OTVT/PVC
      origin was mapped preprocedurally by using ECM, and 3 published ECG algorithms
      were applied to the 12-lead ECG by 3 blinded electrophysiologists. Ablation was
      guided by using ECM. The OTVT/PVC origin was defined as the site where ablation
      caused arrhythmia suppression. Acute success was defined as abolition of ectopy
      after ablation. Medium-term success was defined as the abolition of symptoms and
      reduction of PVC to less than 1000 per day documented on Holter monitoring within
      6 months. RESULTS: In 24 patients (mean age 50 +/- 18 years) recruited ECM
      successfully identified OTVT/PVC origin in 23/24 (96%) (right ventricular outflow
      tract, 18; left ventricular outflow tract, 6), sublocalizing correctly in 100% of
      this cohort. Acute ablation success was achieved in 100% of the cases with medium
      term success in 22 of 24 patients. PVC burden reduced from 21,837 +/- 23,241 to
      1143 +/- 4039 (P < .0001). ECG algorithms identified the correct chamber of
      origin in 50%-88% of the patients and sublocalized within the right ventricular
      outflow tract (septum vs free-wall) in 37%-58%. CONCLUSIONS: ECM can accurately
      identify OTVT/PVC origin in the left and the right ventricle pre- and
      periprocedurally to guide catheter ablation with an accuracy superior to that of
      published ECG algorithms.

PMID- 24440382
TI  - Exome analysis-based molecular autopsy in cases of sudden unexplained death in
      the young.
AB  - BACKGROUND: Postmortem genetic testing (molecular autopsy) for the common long QT
      syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT)
      genes reveals a pathogenic mutation in up to 30% of sudden unexplained death
      (SUD). The role of additional cardiac arrhythmia and cardiomyopathy genes in SUD
      is largely unknown. OBJECTIVE: The purpose of this study was to investigate the
      feasibility and outcomes of performing exome sequencing-based molecular autopsies
      in a cohort of consecutive SUD cases. METHODS: Autopsies performed from 2005 to
      2009 were reviewed for SUD. Postmortem blood was collected, DNA was isolated, and
      whole exome sequencing was performed. Rare sequence variants in cardiac
      arrhythmia and cardiomyopathy genes were sought. RESULTS: There were 50 SUD cases
      aged 1 to 40 years (mean 21.7 +/- 12 years) in the 5-year period, with a male
      predominance of 1.9:1. The most common event at death was "sleep" (48%). Exome
      sequencing in a subgroup of 28 SUD cases revealed 3 rare variations in 3 SUD
      cases (10%; 2 from exome sequencing and 1 from previous Sanger sequencing) in the
      common LQTS genes: a splice site variation and a single base deletion in KCNH2,
      and a missense variation in KCNQ1. Six rare variations in an additional 25 common
      genes of cardiac arrhythmias and cardiomyopathies were identified in 6 SUD (21%).
      CONCLUSION: Exome sequencing-based molecular autopsy is a useful strategy as part
      of the investigation of SUD cases. The findings further expand the role of the
      molecular autopsy in both identifying a cause of death in the decedent and
      evaluating at-risk family relatives.

PMID- 24440383
TI  - Increased photic sensitivity for phase resetting but not melatonin suppression in
      Siberian hamsters under short photoperiods.
AB  - Light regulates a variety of behavioral and physiological processes, including
      activity rhythms and hormone secretory patterns. Seasonal changes in the
      proportion of light in a day (photoperiod) further modulate those functions.
      Recently, short (SP) versus long days (LP) were found to markedly increase light
      sensitivity for phase shifting in Syrian hamsters. To our knowledge, photoperiod
      effects on light sensitivity have not been studied in other rodents, nor is it
      known if they generalize to other circadian responses. We tested whether photic
      phase shifting and melatonin suppression vary in Siberian hamsters maintained
      under LP or SP. Select irradiances of light were administered, and shifts in
      activity were determined. Photic sensitivity for melatonin suppression was
      examined in a separate group of animals via pulses of light across a 4 log-unit
      photon density range, with post-pulse plasma melatonin levels determined via RIA.
      Phase shifting and melatonin suppression were greater at higher irradiances for
      both LP and SP. The lower irradiance condition was below threshold for phase
      shifts in LP but not SP. Melatonin suppression did not vary by photoperiod, and
      the half saturation constant for fitted sigmoid curves was similar under LP and
      SP. Thus, the photoperiodic modulation of light sensitivity for phase shifting is
      conserved across two hamster genera. The dissociation of photoperiod effects on
      photic phase shifting and melatonin suppression suggests that the modulation of
      sensitivity occurs downstream of the common retinal input pathway. Understanding
      the mechanistic basis for this plasticity may yield therapeutic targets for
      optimizing light therapy practices. 

PMID- 24440384
TI  - CD4 T cell defects in the aged: causes, consequences and strategies to
      circumvent.
AB  - Aging leads to reduced immunity, especially adaptive responses. A key deficiency
      is the poor ability to mount robust antibody response. Although intrinsic
      alterations in B cells with age are in part responsible, impaired CD4 T cell help
      makes a major contribution to the poor antibody response. Other CD4 effector
      responses and memory generation are also impaired. We find delayed and reduced
      development of CD4 T follicular help (Tfh) cells in aged mice in response to
      influenza infection with reduction of long-lived plasma cells. When we examine
      CD4 subsets we also find a shift towards Th1 and cytotoxic CD4 (ThCTL) responses.
      We summarize strategies to circumvent the CD4 T cell defect in aged, including
      adjuvants and proinflammatory cytokines. We find that we can strongly enhance
      responses of aged naive CD4 T cells by using Toll-like receptor (TLR) activated
      dendritic cells (DC) as APC in vivo and that this leads to improved germinal
      center B cells and IgG antibody responses. The enhanced response of aged naive
      CD4 T cells is dependent on IL-6 produced by the DC. 

PMID- 24440386
TI  - DNA topoisomerases in mtDNA maintenance and ageing.
AB  - DNA topoisomerases pass DNA strands through each other, a function essential for
      all DNA metabolic processes that create supercoils or entanglements of DNA.
      Topoisomerases play an ambivalent role in nuclear genome maintenance: Deficiency
      compromises gene transcription, replication and chromosome segregation, while the
      inherent DNA-cleavage activity of the enzymes endangers DNA integrity. Indeed,
      many DNA-damaging agents act through enhancing topoisomerase DNA cleavage.
      Mitochondrial DNA (mtDNA) clearly requires topoisomerase activity for
      transcription and replication, because it is a closed, double-stranded DNA
      molecule. Three topoisomerases have so far been found in mammalian mitochondria
      (I, IIbeta, IIIalpha), but their precise role in mtDNA metabolism, mitochondrial
      maintenance and respiratory function remains mostly unclear. It is a reasonable
      surmise that these enzymes exhibit similar ambiguity with respect to genome
      maintenance and gene transcription as their nuclear counterparts. Here, we review
      what is known about the physiological roles of mitochondrial topoisomerases and
      draft three scenarios of how these enzymes possibly contribute to ageing-related
      mtDNA attrition and respiratory chain dysfunction. These scenarios are: mtDNA
      attrition by exogenously stimulated topoisomerase DNA cleavage, unbalancing of
      mitochondrial and nuclear transcription by direct effects on mitochondrial
      transcription, and contributions to enhanced mtDNA entanglement and
      recombination. 

PMID- 24440385
TI  - High TNF-alpha levels in resting B cells negatively correlate with their
      response.
AB  - Aging significantly decreases the influenza vaccine-specific response as we and
      others have previously shown. Based on our previous data in aged mice, we
      hypothesize that the inflammatory status of the individual and of B cells
      themselves would impact B cell function. We here show that the ability to
      generate a vaccine-specific antibody response is negatively correlated with
      levels of serum TNF-alpha. Moreover, human unstimulated B cells from elderly make
      higher levels of TNF-alpha than those from young individuals, and these
      positively correlate with serum TNF-alpha levels. These all negatively correlate
      with B cell function, measured by activation-induced cytidine deaminase, the
      enzyme of class switch recombination and somatic hypermutation. Only memory B
      cells (either IgM or switched), but not naive B cells, make appreciable levels of
      TNF-alpha and more in elderly as compared to young individuals. Finally, an anti
      TNF-alpha antibody can increase the response in cultured B cells from the
      elderly, suggesting that TNF-alpha secreted by memory B cells affects IgM memory
      B cells and naive B cells in an autocrine and/or paracrine manner. Our results
      show an additional mechanism for reduced B cell function in the elderly and
      propose B cell-derived TNF-alpha as another predictive biomarker of in vivo and
      in vitro B cell responses. 

PMID- 24440387
TI  - Naive T cells: the crux of cellular immune aging?
AB  - When encountering foreign antigens, naive T cells become activated and
      differentiate into effector and memory T cells. They represent therefore the
      primary source to mount an immune response against pathogens or tumors. Recent
      evidence of both quantitative and qualitative alterations of naive T cells has
      accumulated in aged mice, indicating that the successful generation of primary T
      cell responses from the naive T cell pool may be compromised with old age.
      However, the vast majority of the data supporting compromised naive T cell
      priming efficacy with old age have been produced in animal models, and the
      situation is much less clear in humans. In the elderly, the involution of the
      thymus and the associated decline in thymic output result in a decreased number
      of naive T cells, which is partially compensated by homeostatic proliferation.
      Emerging evidence suggest that alterations of the TCR repertoire diversity and
      intrinsic defects of old CD4(+) naive T cells may impact on their responsiveness
      to antigenic stimulation. Increasing focus on the study of naive T cells (in
      particular CD8(+)) in old humans are needed to fill the gaps in our understanding
      of reduced cellular immunity with aging. 

PMID- 24440388
TI  - Chronic CMV infection in older women: longitudinal comparisons of CMV DNA in
      peripheral monocytes, anti-CMV IgG titers, serum IL-6 levels, and CMV pp65 (NLV)
      specific CD8(+) T-cell frequencies with twelve year follow-up.
AB  - Chronic cytomegalovirus (CMV) infection may contribute significantly to T-cell
      immunosenescence, chronic inflammation, and adverse health outcomes in older
      adults. Recent studies suggest detectable CMV DNA in peripheral monocytes as a
      better indicator for this persistent viral infection than anti-CMV IgG serology.
      Here, we conducted longitudinal comparisons of anti-CMV IgG titers, CMV DNA in
      the peripheral monocytes, serum IL-6 levels, and CMV pp65 (NLV)-specific CD8(+) T
      cell frequencies in fifteen community-dwelling older women with twelve year
      follow-up. The results showed that anti-CMV IgG titers did not change over twelve
      years. Women with detectable CMV DNA had significantly higher IL-6 levels than
      those without, both at baseline (3.06+/-0.58 vs 1.19+/-0.37pg/ml, respectively,
      p<.001) and at the follow-up (3.23+/-0.66 versus 0.98+/-0.37pg/ml, respectively,
      p<.001). In addition, CMV pp65 (NLV)-specific CD8(+) T cells were detected only
      in women who had CMV DNA with similar frequencies at both time points. These
      findings indicate that anti-CMV IgG serology is neither sensitive to change nor
      useful for monitoring chronic CMV infection over time. They also provide a basis
      for further investigation into chronic CMV infection as defined by detectable CMV
      DNA in the peripheral monocytes and its impact on immunity and health in the
      elderly. 

PMID- 24440390
TI  - Clinical and CT findings in appendiceal diverticulitis.
AB  - Appendiceal diverticulitis is a rare pathologic entity that is difficult to
      diagnose on clinical grounds because of an indolent course and atypical
      presenting symptoms. However, the characteristic computed tomographic (CT)
      features should suggest the correct diagnosis, and an appendectomy should be
      performed. Despite its rarity, radiologists should be aware of this condition and
      the findings on CT because of the higher risk of perforation than in appendicitis
      and the potential association with appendiceal neoplasms. 

PMID- 24440389
TI  - Mechanisms shaping the naive T cell repertoire in the elderly - thymic involution
      or peripheral homeostatic proliferation?
AB  - The ability of the human immune system to repel infections is drastically
      diminished with age. Elderly individuals are more susceptible to new threats and
      are less able to control endogenous infections. The thymus, which is the sole
      source of new T cells, has been proposed as a target for regenerative efforts to
      improve immune competence, as thymic activity is dramatically reduced after
      puberty. In this review, we review the role of the thymus in the maintenance of T
      cell homeostasis throughout life and contrast the differences in mice and humans.
      We propose that in humans, lack of thymic T cell generation does not explain a
      decline in T cell receptor diversity nor would thymic rejuvenation restore
      diversity. Initial studies using next generation sequencing are beginning to
      establish lower boundaries of T cell receptor diversity. With increasing
      sequencing depth and the development of new statistical models, we are now in the
      position to test this model and to assess the impact of age on T cell diversity
      and clonality. 

PMID- 24440392
TI  - Regulation of polyp-to-jellyfish transition in Aurelia aurita.
AB  - BACKGROUND: The life cycle of scyphozoan cnidarians alternates between sessile
      asexual polyps and pelagic medusa. Transition from one life form to another is
      triggered by environmental signals, but the molecular cascades involved in the
      drastic morphological and physiological changes remain unknown. RESULTS: We show
      in the moon jelly Aurelia aurita that the molecular machinery controlling
      transition of the sessile polyp into a free-swimming jellyfish consists of two
      parts. One is conserved and relies on retinoic acid signaling. The second, novel
      part is based on secreted proteins that are strongly upregulated prior to
      metamorphosis in response to the seasonal temperature changes. One of these
      proteins functions as a temperature-sensitive "timer" and encodes the precursor
      of the strobilation hormone of Aurelia. CONCLUSIONS: Our findings uncover the
      molecule framework controlling the polyp-to-jellyfish transition in a basal
      metazoan and provide insights into the evolution of complex life cycles in the
      animal kingdom.

PMID- 24440391
TI  - Cellular and behavioral functions of fruitless isoforms in Drosophila courtship.
AB  - BACKGROUND: Male-specific products of the fruitless (fru) gene control the
      development and function of neuronal circuits that underlie male-specific
      behaviors in Drosophila, including courtship. Alternative splicing generates at
      least three distinct Fru isoforms, each containing a different zinc-finger
      domain. Here, we examine the expression and function of each of these isoforms.
      RESULTS: We show that most fru(+) cells express all three isoforms, yet each
      isoform has a distinct function in the elaboration of sexually dimorphic
      circuitry and behavior. The strongest impairment in courtship behavior is
      observed in fru(C) mutants, which fail to copulate, lack sine song, and do not
      generate courtship song in the absence of visual stimuli. Cellular dimorphisms in
      the fru circuit are dependent on Fru(C) rather than other single Fru isoforms.
      Removal of Fru(C) from the neuronal classes vAB3 or aSP4 leads to cell-autonomous
      feminization of arborizations and loss of courtship in the dark. CONCLUSIONS:
      These data map specific aspects of courtship behavior to the level of single fru
      isoforms and fru(+) cell types-an important step toward elucidating the chain of
      causality from gene to circuit to behavior.

PMID- 24440394
TI  - Alpha stimulation of the human parietal cortex attunes tactile perception to
      external space.
AB  - An intriguing question in neuroscience concerns how somatosensory events on the
      skin are represented in the human brain. Since Head and Holmes' [1]
      neuropsychological dissociation between localizing touch on the skin and
      localizing body parts in external space, touch is considered to operate in a
      variety of spatial reference frames [2]. At least two representations of space
      are in competition during orienting to touch: a somatotopic one, reflecting the
      organization of the somatosensory cortex (S1) [3], and a more abstract, external
      reference frame that factors postural changes in relation to body parts and/or
      external space [4, 5]. Previous transcranial magnetic stimulation (TMS) studies
      suggest that the posterior parietal cortex (PPC) plays a key role in supporting
      representations as well as orienting attention in an external reference frame [4,
      6]. Here, we capitalized on the TMS entrainment approach [7, 8], targeting the
      intraparietal sulcus (IPS). We found that frequency-specific (10 Hz) tuning of
      the PPC induced spatially specific enhancement of tactile detection that was
      expressed in an external reference frame. This finding establishes a tight causal
      link between a concrete form of brain activity (10 Hz oscillation) and a specific
      type of spatial representation, revealing a fundamental property of how the
      parietal cortex encodes information. 

PMID- 24440393
TI  - The SMC condensin complex is required for origin segregation in Bacillus
      subtilis.
AB  - SMC condensin complexes play a central role in organizing and compacting
      chromosomes in all domains of life [1, 2]. In the bacterium Bacillus subtilis,
      cells lacking SMC are viable only during slow growth and display decondensed
      chromosomes, suggesting that SMC complexes function throughout the genome [3, 4].
      Here, we show that rapid inactivation of SMC or its partner protein ScpB during
      fast growth leads to a failure to resolve newly replicated origins and a complete
      block to chromosome segregation. Importantly, the loss of origin segregation is
      not due to an inability to unlink precatenated sister chromosomes by
      Topoisomerase IV. In support of the idea that ParB-mediated recruitment of SMC
      complexes to the origin is important for their segregation, cells with reduced
      levels of SMC that lack ParB are severely impaired in origin resolution. Finally,
      we demonstrate that origin segregation is a task shared by the condensin complex
      and the parABS partitioning system. We propose that origin-localized SMC
      constrains adjacent DNA segments along their lengths, drawing replicated origins
      in on themselves and away from each other. This SMC-mediated lengthwise
      condensation, bolstered by the parABS system, drives origin segregation.

PMID- 24440395
TI  - Plume-tracking behavior of flying Drosophila emerges from a set of distinct
      sensory-motor reflexes.
AB  - BACKGROUND: For a fruit fly, locating fermenting fruit where it can feed, find
      mates, and lay eggs is an essential and difficult task requiring the integration
      of olfactory and visual cues. Here, we develop an approach to correlate flies'
      free-flight behavior with their olfactory experience under different wind and
      visual conditions, yielding new insight into plume tracking based on over 70 hr
      of data. RESULTS: To localize an odor source, flies exhibit three iterative,
      independent, reflex-driven behaviors, which remain constant through repeated
      encounters of the same stimulus: (1) 190 +/- 75 ms after encountering a plume,
      flies increase their flight speed and turn upwind, using visual cues to determine
      wind direction. Due to this substantial response delay, flies pass through the
      plume shortly after entering it. (2) 450 +/- 165 ms after losing the plume, flies
      initiate a series of vertical and horizontal casts, using visual cues to maintain
      a crosswind heading. (3) After sensing an attractive odor, flies exhibit an
      enhanced attraction to small visual features, which increases their probability
      of finding the plume's source. CONCLUSIONS: Due to plume structure and sensory
      motor delays, a fly's olfactory experience during foraging flights consists of
      short bursts of odor stimulation. As a consequence, delays in the onset of
      crosswind casting and the increased attraction to visual features are necessary
      behavioral components for efficiently locating an odor source. Our results
      provide a quantitative behavioral background for elucidating the neural basis of
      plume tracking using genetic and physiological approaches.

PMID- 24440396
TI  - Male-specific fruitless isoforms target neurodevelopmental genes to specify a
      sexually dimorphic nervous system.
AB  - BACKGROUND: In Drosophila, male courtship behavior is regulated in large part by
      the gene fruitless (fru). fru encodes a set of putative transcription factors
      that promote male sexual behavior by controlling the development of sexually
      dimorphic neuronal circuitry. Little is known about how Fru proteins function at
      the level of transcriptional regulation or the role that isoform diversity plays
      in the formation of a male-specific nervous system. RESULTS: To characterize the
      roles of sex-specific Fru isoforms in specifying male behavior, we generated
      novel isoform-specific mutants and used a genomic approach to identify direct Fru
      isoform targets during development. We demonstrate that all Fru isoforms directly
      target genes involved in the development of the nervous system, with individual
      isoforms exhibiting unique binding specificities. We observe that fru behavioral
      phenotypes are specified by either a single isoform or a combination of isoforms.
      Finally, we illustrate the utility of these data for the identification of novel
      sexually dimorphic genomic enhancers and novel downstream regulators of male
      sexual behavior. CONCLUSIONS: These findings suggest that Fru isoform diversity
      facilitates both redundancy and specificity in gene expression, and that the
      regulation of neuronal developmental genes may be the most ancient and conserved
      role of fru in the specification of a male-specific nervous system.

PMID- 24440397
TI  - Visual space is represented by nonmatching topographies of distinct mouse retinal
      ganglion cell types.
AB  - The distributions of neurons in sensory circuits display ordered spatial patterns
      arranged to enhance or encode specific regions or features of the external
      environment. Indeed, visual space is not sampled uniformly across the vertebrate
      retina. Retinal ganglion cell (RGC) density increases and dendritic arbor size
      decreases toward retinal locations with higher sampling frequency, such as the
      fovea in primates and area centralis in carnivores [1]. In these locations,
      higher acuity at the level of individual cells is obtained because the receptive
      field center of a RGC corresponds approximately to the spatial extent of its
      dendritic arbor [2, 3]. For most species, structurally and functionally distinct
      RGC types appear to have similar topographies, collectively scaling their cell
      densities and arbor sizes toward the same retinal location [4]. Thus, visual
      space is represented across the retina in parallel by multiple distinct circuits
      [5]. In contrast, we find a population of mouse RGCs, known as alpha or alpha
      like [6], that displays a nasal-to-temporal gradient in cell density, size, and
      receptive fields, which facilitates enhanced visual sampling in frontal visual
      fields. The distribution of alpha-like RGCs contrasts with other known mouse RGC
      types and suggests that, unlike most mammals, RGC topographies in mice are
      arranged to sample space differentially. 

PMID- 24440398
TI  - Topography of head direction cells in medial entorhinal cortex.
AB  - BACKGROUND: Neural circuits in the medial entorhinal cortex (MEC) support
      translation of the external environment to an internal map of space, with grid
      and head direction neurons providing metrics for distance and orientation.
      RESULTS: We show here that head direction cells in MEC are organized
      topographically. Head direction tuning varies widely across the entire
      dorsoventral MEC axis, but in layer III there is a gradual dorsal-to-ventral
      increase in the average width of the directional firing field. Sharply tuned
      cells were encountered only at the dorsal end of MEC. Similar topography was not
      observed among head direction cells in layers V-VI. At all MEC locations, in all
      layers, the preferred firing direction (directional phase) showed a uniform
      distribution. The continuity of the dorsoventral tuning gradient coexisted with
      discrete topography in the spatial scale of simultaneously recorded grid cells.
      CONCLUSIONS: The findings point to dorsoventral gradients as a fundamental
      property of entorhinal circuits, upon which modular organization may be expressed
      in select subpopulations.

PMID- 24440400
TI  - Image-based analysis of the size- and time-dependent penetration of polymeric
      micelles in multicellular tumor spheroids and tumor xenografts.
AB  - While the heightened tumor accumulation of systemically administered
      nanomedicines relative to conventional chemotherapeutic agents has been well
      established, corresponding improvements in therapeutic efficacy have often been
      incommensurate. This observation may be attributed to the limited exposure of
      cancer cells to therapy due to the heterogeneous intratumoral distribution and
      poor interstitial penetration of nanoparticle-based drug delivery systems. In the
      present work, the spatio-temporal distribution of block copolymer micelles (BCMs)
      of different sizes was evaluated in multicellular tumor spheroids (MCTS) and
      tumor xenografts originating from human cervical (HeLa) and colon (HT29) cancer
      cells using image-based, computational techniques. Micelle penetration was found
      to depend on nanoparticle size, time as well as tumor and spheroid cell line.
      Moreover, spheroids demonstrated the capacity to predict relative trends in
      nanoparticle interstitial transport in tumor xenografts. Overall, techniques are
      presented for the assessment of nanoparticle distribution in spheroids and
      xenografts and used to evaluate the influence of micelle size and cell-line
      specific tissue properties on micelle interstitial penetration. 

PMID- 24440399
TI  - Interlinked sister chromosomes arise in the absence of condensin during fast
      replication in B. subtilis.
AB  - Condensin-an SMC-kleisin complex-is essential for efficient segregation of sister
      chromatids in eukaryotes [1-4]. In Escherichia coli and Bacillus subtilis,
      deletion of condensin subunits results in severe growth phenotypes and the
      accumulation of cells lacking nucleoids [5, 6]. In many other bacteria and under
      slow growth conditions, however, the reported phenotypes are much milder or
      virtually absent [7-10]. This raises the question of what role prokaryotic
      condensin might play during chromosome segregation under various growth
      conditions. In B. subtilis and Streptococcus pneumoniae, condensin complexes are
      enriched on the circular chromosome near the single origin of replication by ParB
      proteins bound to parS sequences [11, 12]. Using conditional alleles of condensin
      in B. subtilis, we demonstrate that depletion of its activity results in an
      immediate and severe defect in the partitioning of replication origins. Multiple
      copies of the chromosome remain unsegregated at or near the origin of
      replication. Surprisingly, the growth and chromosome segregation defects in rich
      medium are suppressed by a reduction of replication fork velocity but not by
      partial inhibition of translation or transcription. Prokaryotic condensin likely
      prevents the formation of sister DNA interconnections at the replication fork or
      promotes their resolution behind the fork.

PMID- 24440401
TI  - Amino acid prodrug of quinidine: an approach to circumvent P-glycoprotein
      mediated cellular efflux.
AB  - In the present study, we investigated the effect of large neutral amino acid
      modification in overcoming P-gp mediated cellular efflux of quinidine. L
      isoleucine ester prodrug of quinidine (Ile-quinidine) was synthesized in our
      laboratory. [14C]-erythromycin was selected as a model substrate to study
      interaction of quinidine and Ile-quinidine with P-gp. Transport studies were
      conducted to study translocation kinetics of quinidine and Ile-quinidine in MDCK
      MDR1 cells. In cellular accumulation study, uptake rate of [14C]-erythromycin
      elevated drastically in presence of cyclosporine A and GF 120918. This result
      indicates that [14C]-erythromycin is an excellent substrate of P-gp. Similarly,
      uptake rate of [14C]-erythromycin was enhanced significantly in presence of
      quinidine (25 and 50 MUM). However, [14C]-erythromycin uptake rate remained
      fairly constant in presence of Ile-quinidine (25 MUM). Apparent A-B and B-A
      permeability of quinidine observed in MDCK-MDR1 cells were 1.6 +/- 0.2 * 10(-6)
      and 7.0 +/- 0.4 * 10(-6)cm/s, a 4.4-fold difference. Moreover, A-B permeability
      of quinidine increased dramatically in the presence of cyclosporine A and GF
      120918. Apparent permeability values of Ile-quinidine observed from A-B and B-A
      direction were 4.3 +/- 0.9 * 10(-6) and 5.5 +/- 0.4 * 10(-6)cm/s, a 1.3-fold
      difference. Importantly, A-B transport of Ile-quinidine did not change
      dramatically in the presence of cyclosporine and GF 120918. Based on these
      results, it was apparent that quinidine displayed higher substrate affinity
      toward P-gp relative to Ile-quinidine. Chemical or enzymatic hydrolysis of Ile
      quinidine resulted in regeneration of low quantities of quinidine during
      transport studies. Competitive inhibition studies demonstrated that Ile-quinidine
      was recognized by multiple amino acid transporters such as LAT1, LAT2 and
      cationic amino acid transporter. In conclusion, chemical modification of
      quinidine with neutral amino acids results in circumvention of P-gp mediated drug
      efflux. Hence, amino acid transporter targeted prodrug delivery seems to be a
      viable strategy for improving drug accumulation in P-gp overexpressing cells.

PMID- 24440402
TI  - Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co
      delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian
      cancer.
AB  - The therapeutic potential of mixed micelles, made of PEG-PE and vitamin E co
      loaded with curcumin and paclitaxel, was investigated against SK-OV-3 human
      ovarian adenocarcinoma along with its multi-drug resistant version SK-OV-3
      paclitaxel-resistant (TR) cells in vitro and in vivo. The addition of curcumin at
      various concentrations did not significantly enhance the cytotoxicity of
      paclitaxel against SK-OV-3 in vitro. However, a clear synergistic effect was
      observed with the combination treatment against SK-OV-3TR in vitro. In vivo, this
      combination treatment produced a three-fold tumor inhibition with each of these
      cell lines. Our results indicate that such co-loaded mixed micelles could have
      significant clinical advantages for the treatment of resistant ovarian cancer. 

PMID- 24440403
TI  - The effect of HPMCAS functional groups on drug crystallization from the
      supersaturated state and dissolution improvement.
AB  - The inhibitory effect on drug crystallization in aqueous solution was evaluated
      using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS).
      HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF),
      mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly
      derived from molecular level hydrophobic interactions between the drug and
      HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug
      crystallization. The inhibition of crystallization was affected by pH, with the
      CBZ crystallization being inhibited at a higher pH due to the hydrophilization of
      HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an
      HPMCAS solution was evaluated by 1D-(1)H NMR and relaxation time measurements.
      CBZ mobility was strongly suppressed in the HPMCAS solutions where strong
      inhibitory effects on CBZ crystallization were observed. The mobility suppression
      of CBZ in the HPMCAS solution was derived from intermolecular interactions
      between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of
      HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid
      dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher
      succinoyl substituent ratio was used. 

PMID- 24440404
TI  - Pharmaceutical characterization and thermodynamic stability assessment of a
      colloidal iron drug product: iron sucrose.
AB  - The study objective was to evaluate the thermodynamic stability of iron sucrose
      complexes as determined by molecular weight (m.w.) changes. The first part of the
      study focused on the effect of thermal stress, pH, electrolyte or excipient
      dilution on the stability of a colloidal iron drug product. Part two focused on
      the physical and chemical evaluation of the colloidal nature of iron sucrose
      using a series of characterization experiments: ultracentrifugation, dialysis,
      particle size, zeta potential, and osmotic pressure analysis. A validated Taguchi
      optimized high performance gel permeation chromatography method was used for m.w.
      determinations. Results indicate m.w. of the iron sucrose complex remained
      unchanged after excipient dilution, ultracentrifugation, dialysis, and
      electrolyte dilution. Electrolyte dilution studies indicated the lyophilic nature
      of the iron sucrose colloid with a particle size of 10nm and zeta potential of 0
      mV. The complex deformed at low pH and reformed back at the formulation pH. The
      complex is stable under mild-to-moderate temperature <50 degrees C but aggregates
      following prolonged exposure to high temperatures >70 degrees C. In conclusion,
      the resistance of the complex to breakdown by electrolytic conditions, excipient
      dilution, ultracentrifugation and the reversible complexation after alteration of
      formulation pH suggest iron sucrose is a lyophilic colloid in nature and
      lyophilic colloidals are thermodynamically stable.

PMID- 24440405
TI  - Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor: chemical
      synthesis, mechanistic studies, and effectiveness in vivo.
AB  - Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of
      recurrence. An improved chemotherapeutic approach is required to complement
      radiation therapy. Gold(I) complexes bearing phosphole ligands are promising
      agents in the treatment of cancer and disturb the redox balance and proliferation
      of cancer cells by inhibiting disulfide reductases. Here, we report on the
      antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold
      chloride thio-beta-d-glucose tetraacetate (GoPI-sugar), which exhibits
      antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines.
      Compared to carmustine (BCNU), an established nitrosourea compound for the
      treatment of glioblastomas that inhibits the proliferation of these glioma cell
      lines with an IC50 of 430MUM, GoPI-sugar is more effective by two orders of
      magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6
      glioma rat model and significantly reduces tumor volume while being well
      tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact
      with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly
      and potently inhibits thioredoxin reductase (IC50 4.3nM) and human glutathione
      reductase (IC50 88.5nM). However, treatment with GoPI-sugar did not significantly
      alter redox parameters in the brain tissue of treated animals. This might be due
      to compensatory upregulation of redox-related enzymes but might also indicate
      that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA
      interaction and inhibition of topoisomerase I than on the disturbance of redox
      equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well
      tolerated, it represents a most promising lead for drug development. This article
      is part of a Special Issue entitled: Thiol-Based Redox Processes. 

PMID- 24440406
TI  - Sequential binding of FurA from Anabaena sp. PCC 7120 to iron boxes: exploring
      regulation at the nanoscale.
AB  - Fur (ferric uptake regulator) proteins are involved in the control of a variety
      of processes in most prokaryotes. Although it is assumed that this regulator
      binds its DNA targets as a dimer, the way in which this interaction occurs
      remains unknown. We have focused on FurA from the cyanobacterium Anabaena sp. PCC
      7120. To assess the molecular mechanism by which FurA specifically binds to "iron
      boxes" in PfurA, we examined the topology arrangement of FurA-DNA complexes by
      atomic force microscopy. Interestingly, FurA-PfurA complexes exhibit several
      populations, in which one is the predominant and depends clearly on the
      regulator/promoter ratio on the environment. Those results together with EMSA and
      other techniques suggest that FurA binds PfurA using a sequential mechanism: (i)
      a monomer specifically binds to an "iron box" and bends PfurA; (ii) two
      situations may occur, that a second FurA monomer covers the free "iron box" or
      that joins to the previously used forming a dimer which would maintain the DNA
      kinked; (iii) trimerization in which the DNA is unbent; and (iv) finally
      undergoes a tetramerization; the next coming molecules cover the DNA strands
      unspecifically. In summary, the bending appears when an "iron box" is bound to
      one or two molecules and decreases when both "iron boxes" are covered. These
      results suggest that DNA bending contributes at the first steps of FurA
      repression promoting the recruitment of new molecules resulting in a fine
      regulation in the Fur-dependent cluster associated genes. 

PMID- 24440407
TI  - Predictors of cardiac troponin release after a marathon.
AB  - OBJECTIVES: Exercise leads to an increase in cardiac troponin I in healthy,
      asymptomatic athletes after a marathon. Previous studies revealed single factors
      to relate to post-race cardiac troponin I levels. Integrating these factors into
      our study, we aimed to identify independent predictors for the exercise-induced
      cardiac troponin I release. DESIGN: Observational study. METHODS: Ninety-two
      participants participated in a marathon at a self-selected speed. Demographic
      data, health status, physical activity levels and marathon experience were
      obtained. Before and immediately after the marathon fluid intake was recorded,
      body mass changes were measured to determine fluid balance and venous blood was
      drawn for analysis of high-sensitive cardiac troponin I. Exercise intensity was
      examined by recording heart rate. We included age, participation in previous
      marathons, exercise duration, exercise intensity and hydration status (relative
      weight change) in our model as potential determinants to predict post-exercise
      cardiac troponin I level. RESULTS: Cardiac troponin I increased significantly
      from 14+/-12 ng/L at baseline to 94+/-102 ng/L post-race, with 69% of the
      participants demonstrating cardiac troponin I levels above the clinical cut-off
      value (40 ng/L) for an acute myocardial infarction. Linear backward regression
      analysis identified younger age (beta=-0.27) and longer exercise duration
      (beta=0.23) as significant predictors of higher post-race cardiac troponin I
      levels (total r=0.31, p<0.05), but not participation in previous marathons,
      relative weight change and exercise intensity. CONCLUSIONS: We found that cardiac
      troponin I levels significantly increased in a large heterogeneous group of
      athletes after completing a marathon. The magnitude of this response could only
      be partially explained, with a lower age and longer exercise duration being
      related to higher post-race cardiac troponin I levels.

PMID- 24440408
TI  - Pharmacologically controlled, discontinuous GDNF gene therapy restores motor
      function in a rat model of Parkinson's disease.
AB  - Neurotrophic factors have raised hopes to be able to cure symptoms and to prevent
      progressive neurodegeneration in devastating neurological diseases. Gene therapy
      by means of viral vectors can overcome the hurdle of targeted delivery, but its
      current configuration is irreversible and thus much less controllable than that
      of classical pharmacotherapies. We thus aimed at developing a strategy allowing
      for both curative and controllable neurotrophic factor expression. Therefore, the
      short-term, intermittent and reversible expression of a neutrophic factor was
      evaluated for therapeutic efficacy in a slowly progressive animal model of
      Parkinson's disease (PD). We demonstrate that short-term induced expression of
      glial cell line derived neurotrophic factor (GDNF) is sufficient to provide i)
      substantial protection of nigral dopaminergic neurons from degeneration and ii)
      restoration of dopamine supply and motor behaviour in the partial striatal 6-OHDA
      model PD. These neurorestorative effects of GDNF lasted several weeks beyond the
      time of its expression. Later on, therapeutic efficacy ceased, but was restored
      by a second short induction of GDNF expression, demonstrating that monthly
      application of the inducing drug mifepristone was sufficient to maintain
      neuroprotective and neurorestorative GDNF levels. These findings suggest that
      forthcoming gene therapies for PD or other neurodegenerative disorders can be
      designed in a way that low frequency application of an approved drug can provide
      controllable and therapeutically efficient levels of GDNF or other neurotrophic
      factors. Neurotrophic factor expression can be withdrawn in case of off-target
      effects or sufficient clinical benefit, a feature that may eventually increase
      the acceptance of gene therapy for less advanced patients, which may profit
      better from such approaches. 

PMID- 24440409
TI  - The neurophysiological index of visual working memory maintenance is not due to
      load dependent eye movements.
AB  - The Contralateral Delayed Activity (CDA) is slow negative potential found during
      a variety of tasks, providing an important measure of the representation of
      information in visual working memory. However, it is studied using stimulus
      arrays in which the to-be-remembered objects are shown in the periphery of the
      left or the right visual field. Our goal was to determine whether fixational eye
      movements in the direction of the memoranda might underlie the CDA. We found that
      subjects' gaze was shifted toward the visual field of the memoranda during the
      retention interval, with its magnitude increasing with the set size. However, the
      CDA was clearly observed even when the subjects' gaze shifts were absent. In
      addition, the magnitude of the subjects' gaze shifts was unrelated to their
      visual working memory capacity measured with behavioral data, unlike the CDA.
      Finally, the onset latency of the set size dependent eye movements followed the
      onset of the set size dependent CDA. Thus, our findings clearly show that the CDA
      does not represent a simple inability to maintain fixation during visual working
      memory maintenance, but that this neural index of representation in working
      memory appears to induce eye movements toward the locations of the objects being
      remembered. 

PMID- 24440410
TI  - Emotional valence and arousal affect reading in an interactive way: neuroimaging
      evidence for an approach-withdrawal framework.
AB  - A growing body of literature shows that the emotional content of verbal material
      affects reading, wherein emotional words are given processing priority compared
      to neutral words. Human emotions can be conceptualised within a two-dimensional
      model comprised of emotional valence and arousal (intensity). These variables are
      at least in part distinct, but recent studies report interactive effects during
      implicit emotion processing and relate these to stimulus-evoked approach
      withdrawal tendencies. The aim of the present study was to explore how valence
      and arousal interact at the neural level, during implicit emotion word
      processing. The emotional attributes of written word stimuli were orthogonally
      manipulated based on behavioural ratings from a corpus of emotion words. Stimuli
      were presented during an fMRI experiment while 16 participants performed a
      lexical decision task, which did not require explicit evaluation of a word's
      emotional content. Results showed greater neural activation within right insular
      cortex in response to stimuli evoking conflicting approach-withdrawal tendencies
      (i.e., positive high-arousal and negative low-arousal words) compared to stimuli
      evoking congruent approach vs. withdrawal tendencies (i.e., positive low-arousal
      and negative high-arousal words). Further, a significant cluster of activation in
      the left extra-striate cortex was found in response to emotional than neutral
      words, suggesting enhanced perceptual processing of emotionally salient stimuli.
      These findings support an interactive two-dimensional approach to the study of
      emotion word recognition and suggest that the integration of valence and arousal
      dimensions recruits a brain region associated with interoception, emotional
      awareness and sympathetic functions. 

PMID- 24440412
TI  - Bioaccumulation of persistent organic pollutants in stranded cetaceans from
      Taiwan coastal waters.
AB  - This study focuses on analyzing PBDEs in the liver, muscle, and blubber tissues
      of stranded dolphins (Stenella attenuate) on the Taiwan coast to determine and
      compare the PBDE levels and distributions among tissue types. Total
      concentrations of 19 PBDEs (SigmaPBDE) in male dolphins (9.97 to 436ng/g fat)
      were significantly higher than in female animals (2.73 to 89.5ng/g fat), implying
      gender variation in bioaccumulation and the possibility of generation transfer
      from mother to fetus during pregnancy. The levels of contamination varied among
      tissue type; contamination was higher in blubber than that in muscle or liver,
      suggesting a possible transformation and redistribution of these compounds in
      body burden. Aside from gender and tissue type, SigmaPBDE concentrations also
      significantly correlated with body length, an indicator of dolphin age. PCA
      analysis results showed no significant difference in PBDE congener pattern
      distributions in blubber tissues, indicating that blubber may be the final
      storage of contaminants in cetaceans, and that bioaccumulation of PBDEs may be
      dependent on chemical properties. BDE-154 and BDE-47 were the predominant PBDE
      congeners in stranded dolphins, and their correlation with body length suggests
      the significant metabolic depletion of BDE-154 in this species and possible
      exposure to both penta-BDE and octa-BDE mixtures. 

PMID- 24440411
TI  - Representation of response alternatives in human presupplementary motor area:
      multi-voxel pattern analysis in a go/no-go task.
AB  - A debate exists as to the role of the presupplementary motor area (preSMA) in
      cognitive control. Recent findings suggest that preSMA plays a central role in
      conflict resolution and encodes response alternatives as opposed to simply the
      presence of conflict. Evidence of neuronal heterogeneity within preSMA of non
      human primates suggests that univariate analysis of functional MRI data may not
      provide adequate resolution to fully characterize cognitive control-related
      responses. Here, multi-voxel pattern analysis (MVPA) is employed to examine the
      distributed patterns of activity in preSMA associated with both successful go
      responses and no-go inhibitions. In a go/no-go task, univariate analysis showed
      undifferentiated activation of preSMA in response to both go and no-go stimuli.
      However, when an anatomically-defined preSMA ROI was subjected to MVPA, a
      significant difference in the activation pattern encoded by go as compared to no
      go stimuli was observed. These differences in preSMA activation are consistent
      with the ongoing maintenance and manipulation of stimulus-action representations.

PMID- 24440413
TI  - Genetic programs controlling cortical interneuron fate.
AB  - The origins of cortical interneurons in rodents have been localized to the
      embryonic subcortical telencephalon where distinct neuroepithelial precursors
      generate defined interneuron subsets. A swathe of research activity aimed at
      identifying molecular determinants of subtype identity has uncovered a number of
      transcription factors that function at different stages of interneuron
      development. Pathways that lead to the acquisition of mature interneuron traits
      are therefore beginning to emerge. As genetic programs are influenced by external
      factors the search continues not only into genetic determinants but also
      extrinsic influences and the interplay between the two in cell fate
      specification. 

PMID- 24440414
TI  - In vivo optogenetic identification and manipulation of GABAergic interneuron
      subtypes.
AB  - Identification and manipulation of different GABAergic interneuron classes in the
      behaving animal are important to understand their role in circuit dynamics and
      behavior. The combination of optogenetics and large-scale neuronal recordings
      allows specific interneuron populations to be identified and perturbed for
      circuit analysis in intact animals. A crucial aspect of this approach is coupling
      electrophysiological recording with spatially and temporally precise light
      delivery. Focal multisite illumination of neuronal activators and silencers in
      predetermined temporal configurations or a closed loop manner opens the door to
      addressing many novel questions. Recent progress demonstrates the utility and
      power of this novel technique for interneuron research. 

PMID- 24440416
TI  - Inhibition and motor control in the developing zebrafish spinal cord.
AB  - Vertebrate locomotion relies on oscillatory activity along the spinal cord.
      Inhibition is involved in controlling the alternation of activity between each
      side and contributes in modulating propagation and termination of locomotor
      activity. Spinal inhibitory neurons are thought to regulate these mechanisms but
      the exact contribution of specific cell types remains difficult to tackle during
      active locomotion. In the past two decades, use of the transparent zebrafish
      larva has enabled morphological, functional, and genetic characterization of
      specific inhibitory spinal neurons. A wide range of new optical tools has been
      developed to monitor and to manipulate the activity of genetically targeted
      spinal populations. Combining these techniques with conventional
      electrophysiology will provide a better understanding of the contribution of
      inhibitory spinal interneurons in regulating essential features of locomotor
      patterns. 

PMID- 24440415
TI  - A blanket of inhibition: functional inferences from dense inhibitory
      connectivity.
AB  - The function of neocortical interneurons is still unclear, and, as often happens,
      one may be able to draw functional insights from considering the structure. In
      this spirit we describe recent structural results and discuss their potential
      functional implications. Most GABAergic interneurons innervate nearby pyramidal
      neurons very densely and without any apparent specificity, as if they were
      extending a 'blanket of inhibition', contacting pyramidal neurons often in an
      overlapping fashion. While subtypes of interneurons specifically target
      subcellular compartments of pyramidal cells, and they also target different
      layers selectively, they appear to treat all neighboring pyramidal cells the same
      and innervate them massively. We explore the functional implications and temporal
      properties of dense, overlapping inhibition by four interneuron populations. 

PMID- 24440417
TI  - The Schistosoma japonicum self-cure phenomenon in water buffaloes: potential
      impact on the control and elimination of schistosomiasis in China.
AB  - Schistosomiasis japonica, caused by Schistosoma japonicum, is an important
      zoonotic disease in China, the Philippines and small pockets of Indonesia. In
      addition to infecting people, S. japonicum can infect over 40 species of wild and
      domestic animals which have varying impacts on human infection. It is now
      generally accepted that bovines, particularly water buffaloes, are the major
      reservoir for human infection in China as they are naturally infected with
      schistosomes and deposit more eggs into the environment than humans or any other
      animal host. This complicates control efforts and the economic burden associated
      with schistosomiasis morbidity and mortality has taken its toll on both human and
      livestock populations. Over the last 50years, the schistosomiasis control program
      in China has made great strides in reducing prevalence and morbidity, and the
      Chinese authorities now aim to eliminate the disease nationwide in the next
      decade. Current Chinese control strategies place particular importance on
      interventions targeting bovines including: praziquantel treatment, barrier
      farming to prevent grazing in transmission areas, their replacement with
      mechanized tractors and possible bovine vaccination. A number of studies have
      shown that in the period following S. japonicum infection, the worm burden drops
      sharply in water buffaloes and some other animal hosts such as pigs. This is due
      to a self-cure phenomenon whereby there is parasite clearance by both immune and
      non-immune factors. Here we review studies investigating the self-cure effect,
      paying particular attention to S. japonicum infection in water buffaloes, and
      discuss its potential impact on the future schistosomiasis control and
      elimination efforts in China. Further understanding of the mechanism of self-cure
      in water buffaloes could be important for future schistosome vaccine design and
      delivery. 

PMID- 24440419
TI  - Transcriptome analysis of the Ophiocordyceps sinensis fruiting body reveals
      putative genes involved in fruiting body development and cordycepin biosynthesis.
AB  - Ophiocordyceps sinensis is a highly valuable and popular medicinal fungus used as
      a tonic and roborant for thousands of years in traditional Asian medicine.
      However, unsustainable harvesting practices have endangered this species and very
      little is known about its developmental programming, its biochemistry and
      genetics. To begin to address this, the transcriptome of the medicinal O.
      sinensis fruiting body was analyzed by high-throughput. In this O. sinensis 454
      EST dataset, four mating type genes and 121 genes that may be involved in
      fruiting body development, especially in signal transduction and transcription
      regulation, were discovered. Moreover, a model was developed for the synthesis of
      the primary medicinal compound, cordycepin, and the putative biosynthetic enzymes
      identified. This transcriptome dataset provides a significant new resource for
      gene discovery in O. sinensis and dissection of its valuable biosynthetic and
      developmental pathways. 

PMID- 24440418
TI  - Microsatellite and mitochondrial markers reveal strong gene flow barriers for
      Anopheles farauti in the Solomon Archipelago: implications for malaria vector
      control.
AB  - Anopheles farauti is the primary malaria vector throughout the coastal regions of
      the Southwest Pacific. A shift in peak biting time from late to early in the
      night occurred following widespread indoor residue spraying of
      dichlorodiphenyltrichloro-ethane (DDT) and has persisted in some island
      populations despite the intervention ending decades ago. We used mitochondrial
      cytochrome oxidase I (COI) sequence data and 12 newly developed microsatellite
      markers to assess the population genetic structure of this malaria vector in the
      Solomon Archipelago. With geographically distinct differences in peak A. farauti
      night biting time observed in the Solomon Archipelago, we tested the hypothesis
      that strong barriers to gene flow exist in this region. Significant and often
      large fixation index (FST) values were found between different island populations
      for the mitochondrial and nuclear markers, suggesting highly restricted gene flow
      between islands. Some discordance in the location and strength of genetic breaks
      was observed between the mitochondrial and microsatellite markers. Since early
      night biting A. farauti individuals occur naturally in all populations, the
      strong gene flow barriers that we have identified in the Solomon Archipelago lend
      weight to the hypothesis that the shifts in peak biting time from late to early
      night have appeared independently in these disconnected island populations. For
      this reason, we suggest that insecticide impregnated bed nets and indoor residue
      spraying are unlikely to be effective as control tools against A. farauti
      occurring elsewhere, and if used, will probably result in peak biting time
      behavioural shifts similar to that observed in the Solomon Islands. 

PMID- 24440420
TI  - Reduction and pH dual-bioresponsive crosslinked polymersomes for efficient
      intracellular delivery of proteins and potent induction of cancer cell apoptosis.
AB  - The clinical applications of protein drugs are restricted because of the absence
      of viable protein delivery vehicles. Here, we report on reduction- and pH-
      sensitive crosslinked polymersomes based on the poly(ethylene glycol)
      poly(acrylic acid)-poly(2-(diethyl amino)ethyl methacrylate) (PEG-PAA-PDEA)
      triblock copolymer for efficient intracellular delivery of proteins and the
      potent induction of cancer cell apoptosis. PEG-PAA-PDEA (1.9-0.8-8.2kgmol(-1))
      was synthesized by controlled reversible addition-fragmentation chain transfer
      polymerization and further modified with cysteamine to yield the thiol-containing
      PEG-PAA(SH)-PDEA copolymer. PEG-PAA(SH)-PDEA was water-soluble at acidic and
      physiological pH but formed robust and monodisperse polymersomes with an average
      size of ~35nm upon increasing the pH to 7.8 or above followed by oxidative
      crosslinking. These disulfide-crosslinked polymersomes, while exhibiting
      excellent colloidal stability, were rapidly dissociated in response to 10mM
      glutathione at neutral or mildly acidic conditions. Notably, these polymersomes
      could efficiently load proteins like bovine serum albumin and cytochrome C (CC).
      The in vitro release studies revealed that protein release was fast and nearly
      quantitative under the intracellular-mimicking reducing environment. Confocal
      microscopy observations showed that these dual-sensitive polymersomes efficiently
      released fluorescein isothiocyanate-CC into MCF-7 cells in 6h. Most remarkably,
      MTT assays showed that CC-loaded dual-sensitive polymersomes induced potent
      cancer cell apoptosis, in which markedly decreased cell viabilities of 11.3%,
      8.1% and 52.7% were observed for MCF-7, HeLa and 293T cells, respectively, at a
      CC dosage of 160MUgml(-1). In contrast, free CC caused no cell death under
      otherwise the same conditions. These dual-bioresponsive polymersomes have
      appeared as a multifunctional platform for active intracellular protein release. 

PMID- 24440421
TI  - Macrophage mannose receptor-specific gene delivery vehicle for macrophage
      engineering.
AB  - Macrophages are the most plastic cells in the hematopoietic system and they
      exhibit great functional diversity. They have been extensively applied in anti
      inflammatory, anti-fibrotic and anti-cancer therapies. However, the application
      of macrophages is limited by the efficiency of their engineering. The macrophage
      mannose receptor (MMR, CD206), a C-type lectin receptor, is ubiquitously
      expressed on macrophages and has a high affinity for mannose oligosaccharides. In
      the present study, we developed a novel non-viral vehicle with specific affinity
      for MMR. Mannan was cationized with spermine at a grafted ratio of ~12% to
      deliver DNA and was characterized as a stable system for delivery. This spermine
      mannan (SM)-based delivery system was evaluated as a biocompatible vehicle with
      superior transfection efficiency on murine macrophages, up to 28.5-fold higher
      than spermine-pullulan, 11.5-fold higher than polyethylenimine and 3.0-fold
      higher than LipofectamineTM 2000. We confirmed that the SM-based delivery system
      for macrophages transfection was MMR-specific and we described the intracellular
      transport of the delivery system. To our knowledge, this is the first study using
      SM to demonstrate a mannose receptor-specific gene delivery system, thereby
      highlighting the potential of a novel specific non-viral delivery vehicle for
      macrophage engineering. 

PMID- 24440422
TI  - In vitro and in vivo evaluation of ultrananocrystalline diamond as an
      encapsulation layer for implantable microchips.
AB  - Thin ultrananocrystalline diamond (UNCD) films were evaluated for use as hermetic
      and bioinert encapsulating coatings for implantable microchips, where the
      reaction to UNCD in vitro and in vivo tissue was investigated. Leakage current
      tests showed that depositing UNCD coatings, which were conformally grown in (1%
      H2) Ar/CH4 plasma, on microchips rendered the surface electrochemically inactive,
      i.e. with a very low leakage current density (2.8*10(-5)Acm(-2) at -1V and
      1.9*10(-3)Acm(-2) at +/-5V) ex vivo. The impact of UNCD with different surface
      modifications on the growth and activation of macrophages was compared to that of
      standard-grade polystyrene. Macrophages attached to oxygen-terminated UNCD films
      down-regulated their production of cytokines and chemokines. Moreover, with UNCD
      coated microchips, which were implanted subcutaneously into BALB/c mice for up to
      3months, the tissue reaction and capsule formation was significantly decreased
      compared to the medical-grade titanium alloy Ti-6Al-4V and bare silicon.
      Additionally, the leakage current density, elicited by electrochemical activity,
      on silicon chips encapsulated in oxygen-terminated UNCD coatings remained at the
      low level of 2.5*10(-3)Acm(-2) at 5V for up to 3months in vivo, which is half the
      level of those encapsulated in hydrogen-terminated UNCD coatings. Thus,
      controlling the surface properties of UNCDs makes it possible to manipulate the
      in vivo functionality and stability of implantable devices so as to reduce the
      host inflammatory response following implantation. These observations suggest
      that oxygen-terminated UNCDs are promising candidates for use as encapsulating
      coatings for implantable microelectronic devices. 

PMID- 24440423
TI  - The basic structure and dynamics of cell membranes: an update of the Singer
      Nicolson model.
AB  - The fluid mosaic model of Singer and Nicolson (1972) is a commonly used
      representation of the cell membrane structure and dynamics. However a number of
      features, the result of four decades of research, must be incorporated to obtain
      a valid, contemporary version of the model. Among the novel aspects to be
      considered are: (i) the high density of proteins in the bilayer, that makes the
      bilayer a molecularly "crowded" space, with important physiological consequences;
      (ii) the proteins that bind the membranes on a temporary basis, thus establishing
      a continuum between the purely soluble proteins, never in contact with membranes,
      and those who cannot exist unless bilayer-bound; (iii) the progress in our
      knowledge of lipid phases, the putative presence of non-lamellar intermediates in
      membranes, and the role of membrane curvature and its relation to lipid geometry,
      (iv) the existence of lateral heterogeneity (domain formation) in cell membranes,
      including the transient microdomains known as rafts, and (v) the possibility of
      transient and localized transbilayer (flip-flop) lipid motion. This article is
      part of a Special Issue entitled: Membrane Structure and Function: Relevance in
      the Cell's Physiology, Pathology and Therapy. 

PMID- 24440424
TI  - Signaling through C2 domains: more than one lipid target.
AB  - C2 domains are membrane-binding modules that share a common overall fold: a
      single compact Greek-key motif organized as an eight-stranded anti-parallel beta
      sandwich consisting of a pair of four-stranded beta-sheets. A myriad of studies
      have demonstrated that in spite of sharing the common structural beta-sandwich
      core, slight variations in the residues located in the interconnecting loops
      confer C2 domains with functional abilities to respond to different Ca(2+)
      concentrations and lipids, and to signal through protein-protein interactions as
      well. This review summarizes the main structural and functional findings on
      Ca(2+) and lipid interactions by C2 domains, including the discovery of the
      phosphoinositide-binding site located in the beta3-beta4 strands. The wide
      variety of functions, together with the different Ca(2+) and lipid affinities of
      these domains, converts this superfamily into a crucial player in many functions
      in the cell and more to be discovered. This Article is Part of a Special Issue
      Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology,
      Pathology and Therapy. 

PMID- 24440425
TI  - Solution structure of the transmembrane domain of the insulin receptor in
      detergent micelles.
AB  - The insulin receptor (IR) binds insulin and plays important roles in glucose
      homeostasis by regulating the tyrosine kinase activity at its C-terminus. Its
      transmembrane domain (TMD) is shown to be important for transferring
      conformational changes induced by insulin across the cell membrane to regulate
      kinase activity. In this study, a construct IR(940-988) containing the TMD was
      expressed and purified for structural studies. Its solution structure in
      dodecylphosphocholine (DPC) micelles was determined. The sequence containing
      residues L962 to Y976 of the TMD of the IR in micelles adopts a well-defined
      helical structure with a kink formed by glycine and proline residues present at
      its N-terminus, which might be important for its function. Paramagnetic
      relaxation enhancement (PRE) and relaxation experimental results suggest that
      residues following the TMD are flexible and expose to aqueous solution. Although
      purified IR(940-988) in micelles existed mainly as a monomeric form verified by
      gel filtration and relaxation analysis, cross-linking study suggests that it may
      form a dimer or oligomers under micelle conditions.

PMID- 24440426
TI  - Membrane composition and dynamics: a target of bioactive virgin olive oil
      constituents.
AB  - The endogenous synthesis of lipids, which requires suitable dietary raw
      materials, is critical for the formation of membrane bilayers. In eukaryotic
      cells, phospholipids are the predominant membrane lipids and consist of
      hydrophobic acyl chains attached to a hydrophilic head group. The relative
      balance between saturated, monounsaturated, and polyunsaturated acyl chains is
      required for the organization and normal function of membranes. Virgin olive oil
      is the richest natural dietary source of the monounsaturated lipid oleic acid and
      is one of the key components of the healthy Mediterranean diet. Virgin olive oil
      also contains a unique constellation of many other lipophilic and amphipathic
      constituents whose health benefits are still being discovered. The focus of this
      review is the latest evidence regarding the impact of oleic acid and the minor
      constituents of virgin olive oil on the arrangement and behavior of lipid
      bilayers. We highlight the relevance of these interactions to the potential use
      of virgin olive oil in preserving the functional properties of membranes to
      maintain health and in modulating membrane functions that can be altered in
      several pathologies. This article is part of a Special Issue entitled: Membrane
      Structure and Function: Relevance in the Cell's Physiology, Pathology and
      Therapy. 

PMID- 24440427
TI  - Can overestimation of walking ability increase the risk of falls in people in the
      subacute stage after stroke on their return home?
AB  - PURPOSE: Falls are common in patients who have had a stroke who return home after
      neurorehabilitation. Some studies have found that walking speed inversely
      correlates with the risk of falls. SCOPE: This study examined whether comparison
      between comfortable self-selected walking speed and maximum maintainable speed is
      informative with regard to the risk of falls in patients with stroke. METHODS: A
      prospective cohort study was performed with 75 ambulant stroke patients. At
      discharge, the Barthel Index score and performance at the 10-m and 6-min walking
      tests were assessed. Number of falls was recorded by telephone interview every
      two months for one year. Regression analysis was performed to identify factors
      that were related to the risk of falls. RESULTS: Using forward multiple linear
      regression, only the ratio between walking speeds on the 6-min and 10-m tests was
      linked to the number of falls in the year after discharge (R=-0.451, p<0.001,
      OR=0.046). Patients who chose a walking speed for short distances that was not
      maintainable long term fell more frequently. CONCLUSIONS: A discrepancy between
      short and long-term walking speed can help in identifying subjects in the
      subacute stage after stroke with an increased risk of suffering a fall.

PMID- 24440428
TI  - Influence of in-shoe heel lifts on plantar pressure and center of pressure in the
      medial-lateral direction during walking.
AB  - The aim of this study was to investigate how the height and material of in-shoe
      heel lifts affect plantar pressure and center of pressure (COP) trajectory in the
      medial-lateral direction during walking. Seventeen healthy young male adults were
      asked to walk along an 8m walkway while wearing a high-cut flat shoe and 5
      different heel lifts. Peak pressure (PP), pressure-time integral (PTI) and
      contact area (CA) were measured by Pedar insole system for three foot regions:
      forefoot, midfoot and heel. Range and velocity of medial-lateral (ML) COP during
      forefoot contact phase (FFCP) and foot flat phase (FFP) were collected using
      Footscan pressure plate. Forefoot pressure and ML-COP parameters increased as the
      heel was elevated. Statistically significant attenuation of heel peak plantar
      pressure was provided by all heel lifts except for the hard lift. Post hoc tests
      suggest that material had a greater influence on the range and velocity of ML-COP
      during FFCP than heel height, while during FFP, heel height seemed to affect
      these parameters more. The findings from this study suggest that thick heel lifts
      should be used with caution, and that a heel lift made of materials with good
      support and elastic properties might be more appropriate to improve footwear
      comfort and medial-lateral motion control.

PMID- 24440430
TI  - Effects of yam tuber protein, dioscorin, on attenuating oxidative status and
      learning dysfunction in d-galactose-induced BALB/c mice.
AB  - The yam tuber is a traditional Chinese medicine used in long-term treatment as a
      juvenescent substance. The purified yam tuber's major water-soluble protein,
      dioscorin, and its protease hydrolysates have been reported to have several
      biological activities. In this study, d-galactose (Gal) was subcutaneously
      injected into the dorsal necks of BALB/c mice daily for 10weeks (Gal group) to
      induce oxidative stress. By the fifth week, 20 or 80mg dioscorin/kg was orally
      administered daily combined with a daily Gal injection until the end of the
      study. The plasma malondialdehyde (MDA) level and advanced glycation end-products
      obtained after dioscorin oral administrations were lower compared to the Gal
      group. In addition, the latency and swimming distance in the mice that received
      dioscorin administration were significantly improved compared to the Gal group in
      the Morris water maze. Dioscorin administration resulted in higher GSH levels and
      oxygen radical antioxidant capacity (ORAC) activity and lower MDA and inducible
      nitric oxide synthase (iNOS) levels in the brain compared to mice in the Gal
      group. These elevated antioxidant activities following oral administration of yam
      dioscorin in vivo may reflect traditional juvenescent uses with the potential for
      anti-aging treatments. 

PMID- 24440432
TI  - Transfer effects between moral dilemmas: a causal model theory.
AB  - Evaluations of analogous situations are an important source for our moral
      intuitions. A puzzling recent set of findings in experiments exploring transfer
      effects between intuitions about moral dilemmas has demonstrated a striking
      asymmetry. Transfer often occurred with a specific ordering of moral dilemmas,
      but not when the sequence was reversed. In this article we present a new theory
      of transfer between moral intuitions that focuses on two components of moral
      dilemmas, namely their causal structure and their default evaluations. According
      to this theory, transfer effects are expected when the causal models underlying
      the considered dilemmas allow for a mapping of the highlighted aspect of the
      first scenario onto the causal structure of the second dilemma, and when the
      default evaluations of the two dilemmas substantially differ. The theory's key
      predictions for the occurrence and the direction of transfer effects between two
      moral dilemmas are tested in five experiments with various variants of moral
      dilemmas from different domains. A sixth experiment tests the predictions of the
      theory for how the target action in the moral dilemmas is represented. 

PMID- 24440431
TI  - Compartmentalization and organelle formation in bacteria.
AB  - A number of bacterial species rely on compartmentalization to gain specific
      functionalities that will provide them with a selective advantage. Here, we will
      highlight several of these modes of bacterial compartmentalization with an eye
      toward describing the mechanisms of their formation and their evolutionary
      origins. Spore formation in Bacillus subtilis, outer membrane biogenesis in Gram
      negative bacteria and protein diffusion barriers of Caulobacter crescentus will
      be used to demonstrate the physical, chemical, and compositional remodeling
      events that lead to compartmentalization. In addition, magnetosomes and
      carboxysomes will serve as models to examine the interplay between cytoskeletal
      systems and the subcellular positioning of organelles. 

PMID- 24440433
TI  - Intentions vs. resemblance: understanding pictures in typical development and
      autism.
AB  - Research has debated whether children reflect on artists' intentions when
      comprehending pictures, or instead derive meaning entirely from resemblance. We
      explore these hypotheses by comparing how typically developing toddlers and low
      functioning children with autism (a population impaired in intentional reasoning)
      interpret abstract pictures. In Experiment 1, both groups mapped familiar object
      names onto abstract pictures, however, they related the same representations to
      different 3-D referents. Toddlers linked abstract pictures with intended
      referents they did not resemble, while children with autism mapped picture
      referent relations based on resemblance. Experiment 2 showed that toddlers do not
      rely upon linguistic cues to determine intended referential relations. Experiment
      3 confirmed that the responding of children with autism was not due to
      perseveration or associative word learning, and also provided independent
      evidence of their intention-reading difficulties. We argue that typically
      developing children derive meaning from the social-communicative intentions
      underlying pictures when resemblance is an inadequate cue to meaning. By
      contrast, children with autism do not reflect on artists' intentions and simply
      relate pictures to whatever they happen to resemble. 

PMID- 24440429
TI  - Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious
      diseases and immunology.
AB  - Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify
      dose-concentration-effect relationships. Within paediatric studies in infectious
      diseases and immunology these methods are often applied to developing guidance on
      appropriate dosing. In this paper, an introduction to the field of PKPD modelling
      is given, followed by a review of the PKPD studies that have been undertaken in
      paediatric infectious diseases and immunology. The main focus is on identifying
      the methodological approaches used to define the PKPD relationship in these
      studies. The major findings were that most studies of infectious diseases have
      developed a PK model and then used simulations to define a dose recommendation
      based on a pre-defined PD target, which may have been defined in adults or in
      vitro. For immunological studies much of the modelling has focused on either PK
      or PD, and since multiple drugs are usually used, delineating the relative
      contributions of each is challenging. The use of dynamical modelling of in vitro
      antibacterial studies, and paediatric HIV mechanistic PD models linked with the
      PK of all drugs, are emerging methods that should enhance PKPD-based
      recommendations in the future. 

PMID- 24440434
TI  - Gene expression profiling of melatonin receptor subtypes in the ovarian
      hierarchical follicles of the Sichuan white goose.
AB  - Melatonin (N-acetyl-5-methoxytryptamine), an indole hormone, regulates a variety
      of important central and peripheral actions related to circadian rhythms and
      reproduction through its specific receptor subtypes (Mel-1a, Mel-1b and Mel-1c).
      However, the expression profile of melatonin receptor genes (MTNR1A, MTNR1B and
      MTNR1C) in ovarian hierarchical follicles of geese remains to be clarified. In
      this study, the expression level of melatonin receptors in small white follicle
      (SWF), small yellow follicle (SYF), the largest follicle (F1), second largest
      (F2), third largest (F3), fourth largest (F4), fifth largest (F5), and
      postovulatory follicle (POF) in the Sichuan white goose were examined using
      quantitative real-time PCR (qRT-PCR). The results showed that the expression
      levels of MTNR1A, MTNR1B and MTNR1C initially increased and later decreased. The
      highest levels of gene expression of these receptor subtypes were observed in F5
      or F4 in all examined follicles. Furthermore, the expression of MTNR1A and MTNR1B
      mRNA was significantly greater in SYF compared with SWF (P<0.05), but MTNR1C was
      absent in SWF. The expression of MTNR1A, MTNR1B and MTNR1C mRNA was significantly
      greater in F5 compared with SYF (P<0.05), and the expression of MTNR1A and MTNR1C
      mRNA was higher in F1 compared with POF (P<0.05). In addition, the oestrogen
      concentration in SWF, SYF, F4, F3, F2, F1 and POF was measured using ELISA. The
      oestrogen concentration and melatonin receptor expression both were initially
      observed to increase and subsequently decrease. The oestrogen concentration in F4
      and F3 was highest in all examined samples and was 1318.2pg/g and 1318.1pg/g,
      respectively. These results suggest that the melatonin receptor may be involved
      in the activation of the SWF and SYF to allow the SWF and SYF to develop into the
      subsequent follicles. Furthermore, follicles and the expression of the melatonin
      receptors may be regulated by the secretion of the oestrogen. 

PMID- 24440435
TI  - Reproductive behavior, embryonic and early larval development of the red head
      goby, Elacatinus puncticulatus.
AB  - The goals of this study are to provide a technical foundation for the production
      of the red head goby Elacatinus puncticulatus by evaluating its reproductive
      behavior and its embryonic and early larval development. Five pairs were kept
      under controlled conditions for thirty days. Courtship behavior, spawning period
      and the number of eggs produced were recorded. For the evaluation of embryo
      development, eggs were sampled at 12, 18, 24, 48, 72, 96, 120, 144 and 168h post
      fertilization(HPF). To test the influence of the incubation period on larval
      total length and height, eggs with six days (6D) of incubation and with seven
      days of incubation (7D) were subjected to flashlight illumination for 30min to
      induce larval hatching. Another experiment evaluated the difference in larval
      survival with three different diets: Euplotes sp. (EU); rotifers Brachionus
      rotundiformis and Brachionus plicatilis and Paramecium sp. (BP); plankton
      collected from the wild (WP). The males displayed a gray head and pale yellow and
      black body coloration. Females exhibited strong red and black colors until three
      days before spawning, which occurred at intervals of 7 to 10 days. The hatching
      rate was 98-99%. The larvae total mean lengths and heights were 3.05 and 2.95mm
      (p>0.05) and 0.37 and 0.48mm (p<0.05) for treatments 6D and 7D, respectively.
      However, both groups exhibited high mortality at 5 days post-hatch (DPH). No
      larvae from the EU group survived after 5 DPH. At 8 DPH, 4% survivorship was
      found in treatment BP and 2% in treatment WP. 

PMID- 24440436
TI  - The Q-VO2 diagram: an analytical interpretation of oxygen transport in arterial
      blood during exercise in humans.
AB  - A new analysis of the relationship between cardiac output (Q) and oxygen
      consumption VO2 is presented (Q-VO2 diagram). Data from different sources in the
      literature have been used for validation in three conditions: exercise and rest
      in normoxia, and exercise in hypoxia. The effects of changes in arterial oxygen
      concentration CaO2 on Q are discussed, as well as the effects of predominant
      sympathetic or vagal stimulation. Differences appear depending on whether CaO2 is
      varied by means of changes in blood haemoglobin concentration or changes in
      arterial oxygen saturation. The present Q-VO2 diagram allows comprehensive
      description of oxygen transport in exercising humans; it expands applicability of
      the historical Q-VO2 relationship to include CaO2 variations; it opens new
      pathways for understanding underlying mechanisms; it allows computation of Q from
      CaO2 and VO2 measurements, when Q cannot be measured.

PMID- 24440437
TI  - Lead contamination and transfer in urban environmental compartments analyzed by
      lead levels and isotopic compositions.
AB  - Lead levels and isotopic compositions in atmospheric particles (TSP and PM2.5),
      street dust and surface soil collected from Nanjing, a mega city in China, were
      analyzed to investigate the contamination and the transfer of lead in urban
      environmental compartments. The lead contents in TSP and PM2.5 are significantly
      higher than them in the surface soil and street dust (p < 0.05). The enrichment
      factor using the mass ratio of lead to the major crustal elements (Al, Sr, Ti and
      Fe) indicates significant lead enrichment in atmospheric particles. The plots of
      (206)Pb/(207)Pb vs.(208)Pb/(206)Pb and (206)Pb/(207)Pb vs. 1/Pb imply that the
      street dust and atmospheric particles (TSP and PM2.5) have very similar lead
      sources. Coal emissions and smelting activities may be the important lead sources
      for street dust and atmospheric particles (TSP and PM2.5), while the deposition
      of airborne lead is an important lead source for urban surface soil. 

PMID- 24440438
TI  - Use of medicinal fauna in Mexican traditional medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Mexico has great biodiversity of fauna. The use
      of fauna with medicinal properties is a common practice since pre-Hispanic times.
      In the last decade, there has been an interest in ethnozoological studies in
      Mexico. Therefore, more studies are needed in order to gather information
      regarding the use of fauna with medicinal properties in Mexico. Ethnozoological
      studies are necessary in order to discover new medications for human health. This
      review presents current information in terms of ethnozoological, conservation
      status, trade, toxicological and pharmacological effects of fauna used for
      medicinal purposes in Mexican traditional medicine (MTM), based on scientific
      literature. Future prospects for research with medicinal fauna are discussed.
      MATERIALS AND METHODS: Bibliographic investigation was carried out by analyzing
      recognized books and peer-reviewed papers, consulting worldwide accepted
      scientific databases from the last five decades. Reports included in this review
      complied with the three criteria cited as follows: (i) used in Mexican
      traditional medicine for medicinal and/or magical-religious purposes, (ii) with
      experimental studies regarding the toxicological or medicinal effects and/or with
      studies exploring mechanisms of medicinal effects, and (iii) with information
      obtained from a clear source. RESULTS: A total of 163 animal species, belonging
      to 79 families and 4 taxonomic categories, used for medicinal purposes are
      reported in this review. Medicinal fauna used in MTM come from birds (48), fishes
      (3), insects (22), mammals (49) and reptiles (41). The most versatile species
      which had the greatest number of medicinal properties were Mephitis macroura (21
      uses), Crotalus atrox (17 uses), Dasypus novemcinctus (13 uses) and Didelphis
      virginiana (13 uses). However, 14 of the 161 species listed in this review are
      classified as endangered. Animal species are mainly used for the treatment of
      inflammatory, respiratory and gastrointestinal diseases. Furthermore, insects and
      reptiles are the animal groups with more pharmacological studies. Approximately,
      11% and 5% of medicinal fauna have been tested in terms of their pharmacological
      and toxicological effects, respectively. CONCLUSION: Despite the use of medicinal
      fauna in MTM, during centuries, there are a very limited number of scientific
      studies published on this topic. This review highlights the need to perform
      pharmacological, toxicological and chemical studies with medicinal fauna used in
      MTM.

PMID- 24440439
TI  - Long-term PT-INR levels and the clinical events in the patients with non-valvular
      atrial fibrillation: a special reference to low-intensity warfarin therapy.
AB  - BACKGROUND: Anticoagulation therapy is essential in atrial fibrillation (AF), and
      in Japan, less intense control is popular. PURPOSE: To assess the efficacy and
      safety with a special reference to low intensity warfarin therapy. SUBJECTS AND
      METHODS: In 488 out of 508 patients with non-valvular AF, prothrombin time
      international normalized ratio (PT-INR) was kept at 1.6-2.59, and they were
      followed for 49.5 months: 2098 person-years. The mean age was 73.7+/-9.9 years
      and 62% were male. The patients were divided by age: >=70 years and <70 years,
      and by the intensity of warfarin therapy: PT-INR at 1.6-1.99 and at 2.0-2.59,
      respectively. The clinical data and event rates, ischemic stroke and major
      bleeding, were compared among the subgroups. RESULTS: Heart failure, previous
      stroke, and higher CHADS2 score were more often reported in patients >=70 years
      while males were involved more often as younger patients. A total of 166 of 339
      patients >=70 years and 69 of 149 patients <70 years belonged to the low
      intensity group. Ischemic stroke and major bleeding occurred in 1.47%/year and
      1.27%/year, respectively but there was no difference between the two age groups
      and between the two intensities of warfarin therapy. Time in therapeutic range
      was a predictor for ischemic stroke. A fall of PT-INR to <1.6 was found in 41.9%
      with ischemic stroke and a rise >2.61 in 40.0% with major bleeding at the time of
      the events. Blunt trauma and concomitant use of antiplatelets were risks for
      intracranial hemorrhage in the patients >=70 years. CONCLUSIONS: The event rates
      were similar between the low- (1.6-1.99) and high- (2.0-2.59) intensity warfarin
      therapy groups in aged patients: <70 years and >=70 years. Time in therapeutic
      range and a transient fall or rise in PT-INR were risks for clinical events.
      Blunt head trauma and concomitant use of antiplatelets were risks for
      intracranial hemorrhage.

PMID- 24440440
TI  - Scopolamine in racing horses: trace identifications associated with dietary or
      environmental exposure.
AB  - Scopolamine (L-hyoscine) identifications, often in small-number clusters, have
      been reported worldwide in performance horses over the last 30 years. Scopolamine
      is an Association of Racing Commissioners International (ARCI) class 3, penalty
      class B, substance with potential to affect performance. As such, scopolamine
      identification(s) in race or performance horses can result in significant
      penalties for the connections of the horse(s). Reviewed here is the worldwide
      distribution of scopolamine containing plants (primarily Datura spp.), with
      estimates of their potential toxicity to horses through dietary and/or
      environmental exposure. Also reviewed are the basic pharmacology of scopolamine
      and its precursor, urinary concentrations following feedstuff exposure, and the
      probable pharmacological/forensic significance of such findings. Based on an
      overview of the world literature on scopolamine, the expected characteristics of
      inadvertent environmental exposure are also presented with a view to making clear
      the potential of scopolamine identifications, with or without atropine, as a
      direct and expected outcome of both the worldwide distribution of scopolamine
      containing plants and the sensitivity of modern equine drug testing. It is of
      particular interest that only 2/30 reported post-event equine identifications of
      scopolamine have been associated with atropine, suggesting that failure to
      identify atropine is not a biomarker of pharmaceutical administration of
      scopolamine. Available quantitative information associated with scopolamine
      identifications is consistent with the 75 ng/mL regulatory threshold for
      scopolamine currently used in Louisiana racing in the USA and the 30 ng/mL
      reporting threshold in effect in European racing.

PMID- 24440441
TI  - Canine epilepsy: in search of a fitting end.

PMID- 24440442
TI  - The potential role of myocardial serotonin receptor 2B expression in canine
      dilated cardiomyopathy.
AB  - Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A
      contribution of serotonin to valvular disease has been reported, but myocardial
      expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not
      known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA
      expression in dogs with DCM and to correlate results with expression of markers
      for inflammation and remodelling. Myocardial samples from eight healthy dogs,
      four dogs with DCM, five with cardiac diseases other than DCM and six with
      systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using
      quantitative PCR (qPCR). The results were compared to mRNA expression of selected
      cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix
      metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and
      immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The
      myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs
      with DCM, 5-HTR2B mRNA values were significantly greater than in all other
      groups, with highest levels of expression in the left ventricle and right atrium.
      Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant
      positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs
      and TIMPs was observed. The findings suggest that serotonin might play a role in
      normal cardiac structure and function and could contribute to myocardial
      remodelling and functional impairment in dogs with DCM. 

PMID- 24440443
TI  - Effects of human adipose-derived stem cells on the viability of rabbit random
      pattern flaps.
AB  - BACKGROUND AIMS: Flap necrosis is the most commonly encountered outcome
      influencing the effect of operations in clinical practice. The advent of
      cytotherapy and regenerative medicine with stem cells, especially adipose-derived
      stem cell therapy, appears to be a promising approach in providing multi-lineage
      differentiating cells. However, autologous stem cells are limited in both
      quantity and quality in aging individuals. Hence, xenogenic stem cell therapy was
      used in this study. METHODS: Random pattern flaps (6 cm * 2 cm) were prepared in
      a rabbit model transplanted either with 4 * 10(5) human adipose-derived stem
      cells at five sites or equal volumes of Dulbecco's modified Eagle's medium. At 7
      days after operation, the viability of the flaps from both groups was evaluated.
      We determined the numbers of locally infiltrating T cells, whereas the CD4/CD8
      ratio, interferon, interleukin (IL)-2, IL-4 and IL-10 in the serum were
      determined to evaluate the immunological response of the rabbit. Moreover, Dil
      labeling was administrated to trace the homing of the transplanted stem cells.
      RESULTS: Both the survival areas and the capillary number of the flaps that were
      injected with human adipose-derived stem cells significantly increased as
      compared with the control group (P < 0.05). Additionally, no significant
      difference in the immune response was detected between the groups. Dil-labeled
      stem cells were found to participate in the formation of tubular structures,
      which were further shown to be CD31+, although not predominantly. CONCLUSIONS:
      Human adipose-derived stem cells could be used therapeutically to improve the
      viability of random pattern flaps without detection of serious immune rejection
      of stem cells.

PMID- 24440444
TI  - Adverse testicular effects of Botox(r) in mature rats.
AB  - Botox(r) injections are taking a consistently increasing place in urology.
      Intracremasteric injections, particularly, have been applied for cryptorchidism
      and painful testicular spasms. Studies outlining their safety for this use are,
      however, scanty. Thus, the present study aimed at evaluating possible testicular
      toxicity of Botox(r) injections and their effect on male fertility. Mature rats
      were given intracremasteric Botox(r) injections (10, 20 and 40 U/kg) three times
      in a two-week interval. Changes in body and testes weights were examined and
      gonadosomatic index compared to control group. Semen quality, sperm parameters,
      fructose, protein, cholesterol and triglycerides contents were assessed. Effects
      on normal testicular function were investigated by measuring testosterone levels
      and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase).
      To draw a complete picture, changes in oxidative and inflammatory states were
      examined, in addition to the extent of connective tissue deposition between
      seminiferous tubules. In an attempt to have more accurate information about
      possible spermatotoxic effects of Botox(r), flowcytometric analysis and
      histopathological examination were carried out. Botox(r)-injected rats showed
      altered testicular physiology and function. Seminiferous tubules were separated
      by dense fibers, especially with the highest dose. Flowcytometric analysis showed
      a decrease in mature sperms and histopathology confirmed the findings. The
      oxidative state was, however, comparable to control group. This study is the
      first to show that intracremasteric injections of Botox(r) induce adverse
      testicular effects evidenced by inhibited spermatogenesis and initiation of
      histopathological changes. In conclusion, decreased fertility may be a serious
      problem Botox(r) injections could cause.

PMID- 24440446
TI  - Giant postnephrectomy arteriovenous fistula in a patient with tuberous sclerosis
      and anomalous inferior vena cava: treatment with amplatzer vascular plug
      embolization.
AB  - A case of 61-year-old woman with tuberous sclerosis complex, who developed a
      fistula between renal artery and renal vein after left-side nephrectomy, was
      presented. In addition, an abnormal course of inferior vena cava was detected
      (type 3 Morito). High-flow fistula was causing volume high output heart failure
      and pulmonary circulation overload with pulmonary hypertension. Because of large
      size of the fistula, it had to be treated with implantation of Amplatzer II to
      the renal artery. The procedure was successfully performed using the brachial
      artery access. 

PMID- 24440445
TI  - A systems toxicology approach identifies Lyn as a key signaling phosphoprotein
      modulated by mercury in a B lymphocyte cell model.
AB  - Network and protein-protein interaction analyses of proteins undergoing Hg2+
      induced phosphorylation and dephosphorylation in Hg2+-intoxicated mouse WEHI-231
      B cells identified Lyn as the most interconnected node. Lyn is a Src family
      protein tyrosine kinase known to be intimately involved in the B cell receptor
      (BCR) signaling pathway. Under normal signaling conditions the tyrosine kinase
      activity of Lyn is controlled by phosphorylation, primarily of two well known
      canonical regulatory tyrosine sites, Y-397 and Y-508. However, Lyn has several
      tyrosine residues that have not yet been determined to play a major role under
      normal signaling conditions, but are potentially important sites for
      phosphorylation following mercury exposure. In order to determine how Hg2+
      exposure modulates the phosphorylation of additional residues in Lyn, a targeted
      MS assay was developed. Initial mass spectrometric surveys of purified Lyn
      identified 7 phosphorylated tyrosine residues. A quantitative assay was developed
      from these results using the multiple reaction monitoring (MRM) strategy. WEHI
      231 cells were treated with Hg2+, pervanadate (a phosphatase inhibitor), or anti
      Ig antibody (to stimulate the BCR). Results from these studies showed that the
      phosphoproteomic profile of Lyn after exposure of the WEHI-231 cells to a low
      concentration of Hg2+ closely resembled that of anti-Ig antibody stimulation,
      whereas exposure to higher concentrations of Hg2+ led to increases in the
      phosphorylation of Y-193/Y-194, Y-501 and Y-508 residues. These data indicate
      that mercury can disrupt a key regulatory signal transduction pathway in B cells
      and point to phospho-Lyn as a potential biomarker for mercury exposure.

PMID- 24440447
TI  - About anecdote.

PMID- 24440448
TI  - Evolutionary aspects of cancer resistance.
AB  - Humans are relatively cancer resistant, as judged by the absence of cancer in two
      thirds of the population. The susceptibility/resistance of other mammalians
      varies but shows no relationship to body size. Selection for longevity and cancer
      resistance may occur in parallel, as indicated by the extremely long lived and
      cancer free mole rat species. Microenvironmental control may play a major role in
      the defense against potential neoplastic cells. Our work confirms that normal
      fibroblasts inhibit the growth of tumor cells in vitro, largely by a contact
      dependent mechanism. The inhibitory capacity of the fibroblast differs depending
      on the site of origin, and is also different between normal and cancer derived
      stroma cells. Preliminary gene analysis points to major differences in gene
      expression in between inhibitory and non-inhibitory fibroblasts. 

PMID- 24440450
TI  - Myosin chaperones.
AB  - The folding and assembly of myosin motor proteins is essential for most movement
      processes at the cellular, but also at the organism level. Importantly, myosins,
      which represent a very diverse family of proteins, require the activity of
      general and specialized folding factors to develop their full motor function. The
      activities of the myosin-specific UCS (UNC-45/Cro1/She4) chaperones range from
      assisting acto-myosin dependent transport processes to scaffolding multi-subunit
      chaperone complexes, which are required to assemble myofilaments. Recent
      structure-function studies revealed the structural organization of TPR
      (tetratricopeptide repeat)-containing and TPR-less UCS chaperones. The observed
      structural differences seem to reflect the specialized and remarkably versatile
      working mechanisms of myosin-directed chaperones, as will be discussed in this
      review. 

PMID- 24440451
TI  - Satisfactory results at 8 years mean follow-up after ADVANCE(r) medial-pivot
      total knee arthroplasty.
AB  - BACKGROUND: Although good overall results have been reported with TKA, certain
      problems and limitations remain, primarily due to postoperative differences in
      joint kinematics, when compared with the normal knee. ADVANCE(r) Medial-Pivot TKA
      involves replicating the medial pivoting behavior observed in normal knees. Here,
      we aimed to investigate the clinical and radiological results and complications
      of TKA using this implant, at mid-term follow-up. METHODS: From January 2001 to
      March 2012, we retrospectively selected 76 patients (85 knees; mean age at
      operation, 70.2+/-8.1 years; range, 51-88 years) with a mean follow-up period of
      93.1+/-14.3 months (range, 72-132 months). Indications for TKA included primary
      degenerative osteoarthritis (60 knees), rheumatoid arthritis (22 knees),
      osteonecrosis (two knees), and osteoarthritis following high tibial osteotomy
      (one knee). The clinical and radiographic results were evaluated. RESULTS: Kaplan
      Meier survivorship analysis indicated a success rate of 98.3% (95% confidence
      interval, 96.6-99.9%). Comparison of pre- and postoperative knee extension angles
      and ranges of motion showed significant improvement postoperatively, in both the
      Knee Society Scores (KSS) and Knee Society Functional Scores (KSFS) (p<0.05). In
      one case, radiographic assessment indicated implant loosening due to infection;
      however, despite this complication, significant improvement of postoperative
      varus or valgus deformity angles were noted in all cases (p<0.05). CONCLUSION:
      Patients undergoing ADVANCE(r) Medial-Pivot TKA achieved excellent clinical and
      radiographic results without any implant-related failures at mid-term follow-up.
      LEVEL OF EVIDENCE: Level IV.

PMID- 24440449
TI  - A review of the bioactivity of hydraulic calcium silicate cements.
AB  - OBJECTIVES: In tissue regeneration research, the term "bioactivity" was initially
      used to describe the resistance to removal of a biomaterial from host tissues
      after intraosseous implantation. Hydraulic calcium silicate cements (HCSCs) are
      putatively accepted as bioactive materials, as exemplified by the increasing
      number of publications reporting that these cements produce an apatite-rich
      surface layer after they contact simulated body fluids. METHODS: In this review,
      the same definitions employed for establishing in vitro and in vivo bioactivity
      in glass-ceramics, and the proposed mechanisms involved in these phenomena are
      used as blueprints for investigating whether HCSCs are bioactive. RESULTS: The
      literature abounds with evidence that HCSCs exhibit in vitro bioactivity;
      however, there is a general lack of stringent methodologies for characterizing
      the calcium phosphate phases precipitated on HCSCs. Although in vivo bioactivity
      has been demonstrated for some HCSCs, a fibrous connective tissue layer is
      frequently identified along the bone-cement interface that is reminiscent of the
      responses observed in bioinert materials, without accompanying clarifications to
      account for such observations. CONCLUSIONS: As bone-bonding is not predictably
      achieved, there is insufficient scientific evidence to substantiate that HCSCs
      are indeed bioactive. Objective appraisal criteria should be developed for more
      accurately defining the bioactivity profiles of HCSCs designed for clinical use.

PMID- 24440452
TI  - Isolation and characterization of alpha-elapitoxin-Bf1b, a postsynaptic
      neurotoxin from Malaysian Bungarus fasciatus venom.
AB  - Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming
      by B. fasciatus results in neurotoxicity due to the presence of presynaptic and
      postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the
      treatment of choice in systemically envenomed patients. In this study, we have
      isolated a postsynaptic neurotoxin which we named alpha-elapitoxin-Bf1b. This
      toxin has an approximate molecular weight of 6.9 kDa, with LCMS/MS data showing
      that it is highly homologous with Neurotoxin 3FTx-RI, a toxin identified in the
      Bungarus fasciatus venom gland transcriptome. alpha-Elapitoxin-Bf1b also shared
      similarity with short-chain neurotoxins from Laticauda colubrina and Pseudechis
      australis. alpha-Elapitoxin-Bf1b produced concentration- and time-dependent
      neurotoxicity in the indirectly-stimulated chick biventer cervicis muscle
      preparation, an effect partially reversible by repetitive washing of the
      preparation. The pA2 value for alpha-elapitoxin-Bf1b of 9.17 +/- 0.64, determined
      by examining the effects of the toxin on cumulative carbacol concentration
      response curves, indicated that the toxin is more potent than tubocurarine and
      alpha-bungarotoxin. Pre-incubation of Bungarus fasciatus monovalent and neuro
      polyvalent antivenom failed to prevent the neurotoxic effects of alpha-elapitoxin
      Bf1b in the chick biventer cervicis muscle preparation. In conclusion, the
      isolation of a postsynaptic neurotoxin that cannot be neutralized by either
      monovalent and polyvalent antivenoms may indicate the presence of isoforms of
      postsynaptic neurotoxins in Malaysian B. fasciatus venom.

PMID- 24440453
TI  - Experimental models of microcystin accumulation in Daphnia magna grazing on
      Planktothrix rubescens: implications for water management.
AB  - In this study, we investigated the kinetic aspects of the microcystin (MC)
      transfer from Planktothrix rubescens to Daphnia magna by carrying out exposure
      experiments in small simple mesocosms. We hypothesized that higher fractions of
      toxic cyanobacteria in the diet of grazers would shift the balance towards a
      greater than linear, i.e. non-linear accumulation of MC in D. magna. This
      hypothesis was tested by exposing D. magna to varying initial densities of MC
      producing P. rubescens. The evolving models of MC accumulation differed largely
      as a result of the duration of exposure and initial MC concentrations used.
      Within the first 24h of exposure, MC accumulation in D. magna was linear,
      irrespective of the initial densities of toxic P. rubescens and thus MC
      concentrations. After 48 h of exposure, MC accumulation in D. magna showed an
      exponential pattern, possibly due to a delayed digestion of P. rubescens and/or
      decreased MC detoxification capabilities when compared with higher ambient
      concentrations of MC. After 72 h toxin concentrations in Daphnia drop in all
      experiments as a consequence of the reduced cyanobacterial cells in the medium
      and the detoxification of MC within Daphnia. The results obtained suggest that in
      lakes with higher MC content and longer cyanobacterial bloom period MC
      accumulation in D. magna should be more pronounced than in mesotrophic lakes with
      lower MC content. The latter interpretation, however, should be verified
      investigating accumulation of MC both in larger mesocosms and in situ, in lakes
      of different trophic status.

PMID- 24440454
TI  - Cellular membrane accommodation of copper-induced oxidative conditions in the
      coral Seriatopora caliendrum.
AB  - Oxidative stress has been associated with copper-induced toxicity in
      scleractinian corals. To gain insight into the accommodation of the cellular
      membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum,
      was exposed to copper at distinct, environmentally relevant dose for various
      lengths of time. Glycerophosphocholine profiling of the response of the coral to
      copper exposure was characterized using a validated method. The results indicate
      that coral lipid metabolism is programmed to induce membrane alterations in
      response to the cellular deterioration that occurs during the copper exposure
      period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated
      phosphatidylcholines for polyunsaturated plasmanylcholines were the initial
      actions taken to prevent membrane permeabilization. To relax/resist the resulting
      membrane strain caused by cell/organelle swelling, the coral cells inversely
      exchanged polyunsaturated plasmanylcholines for polyunsaturated
      phosphatidylcholines and further increased the levels of monounsaturated
      glycerophosphocholines. At the same time, the levels of saturated
      phosphatidylcholines were also increased to increase membrane rigidity and
      protect against oxidative attack. Interestingly, such alterations in lipid
      metabolism were also required for membrane fusion to repair the deteriorated
      membranes by repopulating them with proximal lipid reservoirs, similar to
      symbiosome membranes. Additionally, increasing saturated and monounsaturated
      plasmanylcholines and inhibiting the suppression of saturated lyso
      phosphatidylcholines were shown to facilitate membrane fusion. Based on the
      biochemical and biophysical properties of these lipids, the chronic effects of
      copper, such as coral resistance and growth, can be logically interpreted to
      result from long-term perturbations in cellular membrane-related functions. In
      conclusion, the cells of S. caliendrum alter their lipid metabolism and sacrifice
      fitness to allow the membrane to accommodate copper-induced oxidative situations.

PMID- 24440455
TI  - Signaling by S-nitrosylation in the heart.
AB  - Nitric oxide is a gaseous signaling molecule that is well-known for the Nobel
      prize-winning research that defined nitric oxide as a physiological regulator of
      blood pressure in the cardiovascular system. Nitric oxide can signal via the
      classical pathway involving activation of guanylyl cyclase or by a post
      translational modification, referred to as S-nitrosylation (SNO) that can occur
      on cysteine residues of proteins. As proteins with cysteine residues are common,
      this allows for amplification of the nitric oxide signaling. This review will
      focus on the possible mechanisms through which SNO can alter protein function in
      cardiac cells, and the role of SNO occupancy in these mechanisms. The specific
      mechanisms that regulate protein SNO, including redox-dependent processes, will
      also be discussed. This article is part of a Special Issue entitled "Redox
      Signalling in the Cardiovascular System". 

PMID- 24440457
TI  - Cardioprotection by remote ischemic preconditioning of the rat heart is mediated
      by extracellular vesicles.
AB  - Remote ischemic preconditioning (RIPC) of the heart is exerted by brief ischemic
      insults affected on a remote organ or a remote area of the heart before a
      sustained cardiac ischemia. To date, little is known about the inter-organ
      transfer mechanisms of cardioprotection by RIPC. Exosomes and
      microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in
      diameter, respectively (collectively termed extracellular vesicles [EVs]). Their
      content of proteins, mRNAs and microRNAs, renders EV ideal conveyors of inter
      organ communication. However, whether EVs are involved in RIPC, is unknown.
      Therefore, here we investigated whether (1) IPC induces release of EVs from the
      heart, and (2) EVs are necessary for cardioprotection by RIPC. Hearts of male
      Wistar rats were isolated and perfused in Langendorff mode. A group of donor
      hearts was exposed to 3 * 5-5 min global ischemia and reperfusion (IPC) or 30 min
      aerobic perfusion, while coronary perfusates were collected. Coronary perfusates
      of these hearts were given to another set of recipient isolated hearts. A group
      of recipient hearts received IPC effluent depleted of EVs by differential
      ultracentrifugation. Infarct size was determined after 30 min global ischemia and
      120 min reperfusion. The presence or absence of EVs in perfusates was confirmed
      by dynamic light scattering, the EV marker HSP60 Western blot, and electron
      microscopy. IPC markedly increased EV release from the heart as assessed by
      HSP60. Administration of coronary perfusate from IPC donor hearts attenuated
      infarct size in non-preconditioned recipient hearts (12.9 +/- 1.6% vs. 25.0 +/-
      2.7%), similarly to cardioprotection afforded by IPC (7.3 +/- 2.7% vs. 22.1 +/-
      2.9%) on the donor hearts. Perfusates of IPC hearts depleted of EVs failed to
      exert cardioprotection in recipient hearts (22.0 +/- 2.3%). This is the first
      demonstration that EVs released from the heart after IPC are necessary for
      cardioprotection by RIPC, evidencing the importance of vesicular transfer
      mechanisms in remote cardioprotection.

PMID- 24440456
TI  - Cardiac fibroblasts protect cardiomyocytes against lethal ischemia-reperfusion
      injury.
AB  - Roles of cardiac fibroblasts (CFs) in the regulation of myocardial structure and
      function have been emphasized in the last decade. Their implications in
      pathophysiological aspects of chronic heart diseases such as myocardial
      remodeling and fibrosis are now well established; however their contribution to
      the acute phase of ischemia-reperfusion injury still remains elusive. We
      hypothesized that CF may contribute to cardiomyocyte (CM) protection against
      ischemia-reperfusion injuries. Experiments performed on isolated neonatal rat CF
      and CM demonstrated that the presence of CF in co-cultures increases CM viability
      (58 +/- 2% versus 30 +/- 2% in control) against hypoxia-reoxygenation injury, in
      a paracrine manner. It was confirmed by a similar effect of hypoxic CF secretome
      alone on CM viability (51 +/- 9% versus 31 +/- 4% in untreated cells). These
      findings were corroborated by in vivo experiments in a mice model of myocardial
      infarction in which a 25% infarct size reduction was observed in CF secretome
      treated mice compared to control. Tissue inhibitor of metalloproteinases-1 (TIMPs
      1) alone, abundantly detected in CF secretome, was able to decrease CM cell death
      (35%) and experiments with pharmacological inhibitors of PI3K/Akt and ERK1/2
      pathways provided more evidence that this paracrine protection is partly mediated
      by these signaling pathways. In vivo experiments strengthened that TIMP-1 alone
      was able to decrease infarct size (37%) and were validated by depletion
      experiments demonstrating that CF secretome cardioprotection was abolished by
      TIMP-1 depletion. Our data demonstrated for the first time that CFs participate
      in cardioprotection during the acute phase of ischemia-reperfusion via a
      paracrine pathway involving TIMP-1.

PMID- 24440459
TI  - Isolation and characterization of peptides with dipeptidyl peptidase-IV
      inhibitory activity from pepsin-treated bovine whey proteins.
AB  - Inhibition of the enzyme dipeptidyl peptidase (DPP)-IV is one of the strategies
      used for the treatment of type 2 diabetes. In the present study, pepsin-treated
      whey protein isolate (WPI) and alpha-lactalbumin displaying DPP-IV inhibitory
      activity were fractionated by successive chromatographic steps and the resulting
      active fractions analyzed for their constituent peptides by liquid chromatography
      electrospray ionization-tandem mass spectrometry. Among the identified sequences,
      24 peptides derived from alpha-lactalbumin and 11 from beta-lactoglobulin were
      synthesized and their effects on DPP-IV activity assessed. The most potent
      fragments, LKPTPEGDL and LKPTPEGDLEIL (IC50=45 and 57 MUM, respectively), were
      found to inhibit DPP-IV in an un-competitive manner. Although several of the
      peptides tested showed some inhibitory activity, only two were as effective as
      the un-fractionated WPI hydrolysate and none were as potent as the un
      fractionated alpha-lactalbumin hydrolysate. The peptides' structural features,
      including length and amino acid composition, were found to impact their
      inhibitory activity. This study provides new insights on the active components
      responsible for the DPP-IV inhibitory activity of pepsin-treated whey proteins.

PMID- 24440458
TI  - Microsurgery and radiosurgery for brainstem cavernomas: effective and
      complementary treatment options.
AB  - OBJECTIVE: To evaluate treatment options for brainstem cavernous malformations
      (BSCMs) using the results from a center with long-standing experience in
      microsurgical resection and Gamma Knife radiosurgery (GKRS) treatment of BSCMs.
      METHODS: Study participants were 67 symptomatic patients with BSCMs who were
      treated either microsurgically (n = 29) or radiosurgically (n = 38). Patients
      were followed for a minimum of 2 years (median, 7.7 years). A recent follow-up
      was performed. RESULTS: Patients receiving surgical treatment had mainly large,
      superficially seated lesions and experienced preoperative hemorrhages more often
      and presented with higher preoperative modified Rankin Scale scores. Patients
      receiving GKRS harbored smaller, deep-seated lesions, reflecting a selection
      bias. In both treatment groups, patients presented with significantly better
      modified Rankin Scale scores at follow-up than before intervention. Overall
      annual preoperative hemorrhage rates were 3.2% in microsurgery patients and 2.3%
      in radiosurgery patients. In the preoperative observation period, the
      rehemorrhage rate was 25.1% for microsurgery patients and 7.2% for radiosurgery
      patients. Hemorrhage rate after GKRS decreased significantly to 0.6% after 2
      years. The postoperative hemorrhage rate was 8.8% but only for microsurgery
      patients with residual lesions. Advancements in microsurgical techniques improved
      surgical outcomes, resulting in a high total excision rate in the modern era.
      CONCLUSIONS: In the treatment of BSCM, patient selection and timing of surgery
      are crucial. If applied in a multidisciplinary neurosurgical center, microsurgery
      and radiosurgery are complementary treatment options that both result in reduced
      bleeding rates and improvement of clinical outcome.

PMID- 24440460
TI  - Structural and denaturation studies of two mutants of a cold adapted superoxide
      dismutase point to the importance of electrostatic interactions in protein
      stability.
AB  - A peculiar feature of the psychrophilic iron superoxide dismutase from
      Pseudoalteromonas haloplanktis (PhSOD) is the presence in its amino acid sequence
      of a reactive cysteine (Cys57). To define the role of this residue, a structural
      characterization of the effect of two PhSOD mutations, C57S and C57R, was
      performed. Thermal and denaturant-induced unfolding of wild type and mutant PhSOD
      followed by circular dichroism and fluorescence studies revealed that C->R
      substitution alters the thermal stability and the resistance against denaturants
      of the enzyme, whereas C57S only alters the stability of the protein against
      urea. The crystallographic data on the C57R mutation suggest an involvement of
      the Arg side chain in the formation of salt bridges on protein surface. These
      findings support the hypothesis that the thermal resistance of PhSOD relies on
      optimization of charge-charge interactions on its surface. Our study contributes
      to a deeper understanding of the denaturation mechanism of superoxide dismutases,
      suggesting the presence of a structural dimeric intermediate between the native
      state and the unfolded state. This hypothesis is supported by the crystalline and
      solution data on the reduced form of the enzyme. 

PMID- 24440461
TI  - More pieces to the puzzle: recent structural insights into class II transcription
      initiation.
AB  - Class II transcription initiation is a highly regulated process and requires the
      assembly of a pre-initiation complex (PIC) containing DNA template, RNA
      polymerase II (RNAPII), general transcription factors (GTFs) TFIIA, TFIIB, TFIID,
      TFIIE, TFIIF, TFIIH and Mediator. RNAPII, TFIID, TFIIH and Mediator are large
      multiprotein complexes, each containing 10 and more subunits. Altogether, the PIC
      is made up of about 60 polypeptides with a combined molecular weight of close to
      4MDa. Recent structural studies of key PIC components have significantly advanced
      our understanding of transcription initiation. TFIID was shown to bind promoter
      DNA in a reorganized state. The architecture of a core-TFIID complex was
      elucidated. Crystal structures of the TATA-binding protein (TBP) bound to TBP
      associated factor 1 (TAF1), RNAPII-TFIIB complexes and the Mediator head module
      were solved. The overall architectures of large PIC assemblies from human and
      yeast have been determined by electron microscopy (EM). Here we review these
      latest structural insights into the architecture and assembly of the PIC, which
      reveal exciting new mechanistic details of transcription initiation. 

PMID- 24440462
TI  - Effect of age and CMV on NK cell subpopulations.
AB  - NK cells represent an important component of the innate immune response against
      infection and tumors. Age-associated changes in NK cell phenotype have been
      previously reported that can be responsible of functional NK cell deficiency. The
      aim of this work was to analyze the effect CMV seropositivity and aging on the
      distribution of NK cell subsets with a focus on the expression of cytotoxicity
      related molecules and on the expression of CD94/NKG2 heterodimers and CD57 on
      these NK cell subsets. Our results show that CMV seropositivity in young
      individuals does not significantly affect peripheral blood NK cell percentage and
      NK cell subsets defined by the use of CD56 and CD16 markers. In contrast a
      significant increase in the percentage of NK cells is observed in elderly donors,
      all of them are CMV seropositive, when compared with young CMV seropositive
      subjects. A decrease in the percentage of CD56bright NK cells, either fully
      immature CD16 negative or CD16+ and an increase in the CD56-CD16+ subset are also
      found in the elderly. CMV seropositivity either in healthy young or elderly
      individuals is associated to the expression of CD94/NKG2C dimers and high
      expression of CD57on the CD56dimCD16+ NK cell subset. CD56-CD16+ NK cells, which
      are expanded in the elderly, show a decreased expression of granzymes A and B and
      an increased expression of CD94/NKG2C and CD57 in CMV seropositive young donors
      when compared with CMV seronegative young individuals. These results indicate
      that CMV and age have a different effect on NK cell phenotype and emphasize the
      relevance of including the determination of CMV serostatus in those studies
      addressed to analyze the immune response in the elderly. 

PMID- 24440464
TI  - Comorbidity between headache and epilepsy in a Chinese epileptic center.
AB  - Here we investigated the characteristics and prevalence of headaches in patients
      with epilepsy in a Chinese epileptic center based on the International
      Classification of Headache Disorders, 2nd edition. We found that 60.14%
      (667/1109) of patients reported headaches. Headache was less prevalent in males
      (57.17%) than in females (63.75%). Interictal headaches were present in 34.62% of
      patients, and 139/1109 (12.53%) patients had interictal migraine, which was a
      higher percentage than reported in a large population-based study from the same
      area (9.3%) using the same screening question. In addition, 469 (70.31%) patients
      had postictal headache, migraine characteristics were present in 73.35% of these
      patients, and 15.35% also suffered from interictal migraine. Lastly, 8.85%
      patients had preictal headache. These results confirm that headache is very
      common in patients with epilepsy. Seizures often trigger postictal headaches with
      migraine features. The comorbidity of migraines and epilepsy should receive
      clinical attention, as it may influence antiepileptic drug choice, and the
      headache may require specific treatment. 

PMID- 24440465
TI  - Lysosomal Disease Network's WORLD SymposiumTM 2014.

PMID- 24440463
TI  - Elevated A20 contributes to age-dependent macrophage dysfunction in the lungs.
AB  - Advanced age is associated with chronic low-grade inflammation (i.e. inflamm
      aging) and poor macrophage function that includes a weak pro-inflammatory
      cytokine response to bacteria and diminished phagocytosis (i.e. age-dependent
      macrophage dysfunction [ADMD]). One reason for this is that ADMD is associated
      with poor NFkappaB and MAPK activation following Toll-like receptor stimulation.
      Herein, we tested the hypothesis that inflamm-aging induces production of A20, a
      cytosolic and homeostatic suppressor of the NFkappaB and MAPK signaling cascades
      that deubiquitinates (i.e. inactivates) the common upstream signaling molecule
      TRAF6, and this is responsible for ADMD. Western blots and immunohistochemistry
      comparing tissues from young, mature, and aged C57BL/6 mice indicated that A20
      was strongly elevated in the lungs of aged mice but not in other tissues.
      Elevated A20 was also detected in alveolar macrophages (AM) from aged mice. In
      contrast CYLD, a second deubiquitinase that also negatively regulates the
      NFkappaB pathway was decreased with aging. Following co-incubation of AM with the
      bacteria Streptococcus pneumoniae, TRAF6 polyubiquitination was diminished in AM
      isolated from aged versus young mice. A20 production was inducible in the J774A.1
      macrophage cell line and C57BL/6AM by overnight incubation with TNFalpha but not
      IL-6. Retrovirus-induced expression of A20 in J774A.1 cells resulted in their
      diminished production of IL-6 following exposure to S. pneumoniae but had no
      effect on levels of phagocytosis. Overnight incubation of AM from young mice with
      TNFalpha also resulted in a dampened IL-6 response to S. pneumoniae. Finally,
      dietary supplementation of aged mice with anti-inflammatory n-3 polyunsaturated
      fatty acids in the form of fish oil lowered lung A20 levels and enhanced
      resistance, including a 100-fold reduction in bacterial titers in the lungs, to
      experimental challenge with S. pneumoniae. We conclude that elevated A20 due to
      TNFalpha partially explains the ADMD phenotype and that ADMD is potentially
      reversible. 

PMID- 24440466
TI  - A new gel formulation of topical cysteamine for the treatment of corneal cystine
      crystals in cystinosis: the Cystadrops OCT-1 study.
AB  - OBJECTIVE: To establish the safety and efficacy of a new gel formulation of
      cysteamine hydrochloride (CH) eye drops, for the treatment of corneal
      complications of nephropathic cystinosis. DESIGN: Open label dose response
      clinical trial. PARTICIPANTS: Eight patients with infantile nephropathic
      cystinosis including 4 children, 3 adolescents, and 1 adult (mean age at
      inclusion, 12.1 +/- 4.6 years) treated with CH 0.1% eye drops. INTERVENTION:
      Patients were treated, in both eyes, with the control CH 0.1% eye drop
      formulation on average 4 times daily for one month and then switched to
      Cystadrops(r) at the same dose frequency. Based on clinical ocular findings, the
      dose regimen was adapted at D30 and D90 in order to decrease the frequency of
      instillation. After D90, this dose frequency was maintained, except in cases of
      crystal density worsening. Patients had a follow-up visit every 6 months during
      48 months. MAIN OUTCOME MEASURES: Safety assessment consisted of adverse event
      and serious adverse event monitoring and recording at each visit. For the
      efficacy study, the primary endpoint was the corneal cystine crystal density
      measured with an in vivo confocal microscopy (IVCM) score. RESULTS: All patients
      completed the study. During the 4-year study period, neither serious adverse
      events nor significant adverse events related to the study drug were reported.
      After switching to Cystadrops(r), the IVCM total score decreased from baseline to
      D90 by a mean of 28.6 +/- 17.5% (p<0.001). From D90 to M48, the IVCM total score
      remained stable and significantly decreased as compared to that at D1 despite a
      reduced dose regimen from D90. At M48, the mean IVCM total score was 8.13 +/-
      4.15, decreased by a mean 29.9 +/- 26.29% from D1 (p = 0.001), with a reduced
      number of instillations compared to that at D1. The IVCM total score and
      photophobia were significantly correlated (p = 0.04). CONCLUSION: This study
      provides evidence that Cystadrops(r) gel is superior to the CH 0.1% formulation
      in terms of efficacy and has a good safety profile over a long follow-up period.

PMID- 24440467
TI  - Significance of the rapid increase in GSH levels in the protective response to
      cadmium exposure through phosphorylated Nrf2 signaling in Jurkat T-cells.
AB  - Although cadmium (Cd) is a redox system disruptor, the systematic defensive
      responses to Cd-induced oxidative stress remain unclear. In this study, we
      initially determined that when human T-cell-derived Jurkat cells were exposed to
      a low concentration of Cd, the glutathione (GSH) concentration rapidly increased
      via the transient nuclear accumulation of the transcription factor Nrf2.
      Therefore, we hypothesized that this increase in the GSH levels was a significant
      event that occurred in response to the Cd toxicity in the Jurkat T-cells. To test
      this hypothesis, the expression of Nrf2 in the cells was silenced using siRNA
      transfection. These restricted expression conditions demonstrated that the
      sensitivity of the Jurkat T-cells to Cd toxicity was significantly higher in the
      knockdown cells. Whereas we could not find differences in the metallothionein
      (MT) expression responses, accumulation of Nrf2 in the nuclei and the GSH
      increase after Cd exposure were clearly suppressed in the Nrf2 knockdown cells.
      These findings strongly suggest that the Cd-induced activation of GSH synthesis
      is initiated as an acute response for Cd detoxification. Furthermore, the Cd
      remaining in the Jurkat T-cells did not cause a significant inhibition of cell
      growth after the rapid and transient increase in the GSH concentration returned
      to its basal level. Additionally, we found that MT expression induced by Cd
      occurred much later, with the expression seen at least 12h or more after the Nrf2
      dependent immediate responses were almost completed. These results indicate that
      the rapid increase in GSH is an essential defensive response, with the subsequent
      induction of MT potentially chelating the Cd retained in the cell, thereby
      leading to continued suppression of Cd toxicity. 

PMID- 24440468
TI  - Excreted Leishmania peruviana and Leishmania amazonensis iron-superoxide
      dismutase purification: specific antibody detection in Colombian patients with
      cutaneous leishmaniasis.
AB  - Leishmania sp. survival in the vertebrate host depends on the host macrophage
      immune response as well as on the parasite's defense against free radicals. Iron
      superoxide dismutase (Fe-SOD) is a key antioxidant enzyme that contributes to
      radical superoxide dismutation, preventing the disease from surging and
      propagating itself. Leishmania sp. has various Fe-SOD isoforms, one of which (Fe
      SODe) is excreted into the medium and, being highly immunogenic, can be
      considered a very good molecular marker. In this work, we purified the Fe-SOD
      enzymes excreted by L. peruviana and L. amazonensis and studied them as antigens
      in serodiagnosis. We used ELISA and Western blot techniques to test 51 human
      cutaneous leishmaniasis sera from Colombia. All 51 patients presented with dermal
      injuries caused by unknown Leishmania species. The results observed with the
      purified proteins were compared with those obtained when total soluble lysate and
      unpurified Fe-SODe were used as the antigen fraction. Thus, we conclude that the
      purified enzymes are more sensitive and specific than their unpurified
      counterparts and that there is no cross-reactivity between them. 

PMID- 24440469
TI  - Oxymatrine prevents hypoxia- and monocrotaline-induced pulmonary hypertension in
      rats.
AB  - Pulmonary hypertension is a progressive disease characterized by marked pulmonary
      arterial remodeling and increased vascular resistance. Inflammation and oxidative
      stress promote the development of pulmonary hypertension. Oxymatrine, one of the
      main active components of the Chinese herb Sophora flavescens Ait. (Kushen),
      plays anti-inflammatory and antioxidant protective roles, which effects on
      pulmonary arteries remain unclear. This study aimed to investigate the effects of
      oxymatrine on pulmonary hypertension development. Sprague-Dawley rats were
      exposed to hypoxia for 28 days or injected with monocrotaline, to develop
      pulmonary hypertension, along with administration of oxymatrine (50mg/kg/day).
      Hemodynamics and pulmonary arterial remodeling data from the rats were then
      obtained. The antiproliferative effect of oxymatrine was verified by in vitro
      assays. The inflammatory cytokine mRNA levels and leukocyte and T cell
      accumulation in lung tissue were detected. The antioxidative effects of
      oxymatrine were explored in vitro. Our study shows that oxymatrine treatment
      attenuated right-ventricular systolic pressure and pulmonary arterial remodeling
      induced by hypoxia or monocrotaline and inhibited proliferation of pulmonary
      arterial smooth muscle cells (PASMCs). Increased expression of inflammatory
      cytokine mRNA and accumulation of leukocytes and T cells around the pulmonary
      arteries were suppressed with oxymatrine administration. Under hypoxic
      conditions, oxymatrine significantly upregulated Nrf2 and antioxidant protein
      SOD1 and HO-1 expression, but downregulated hydroperoxide levels in PASMCs. In
      summary, this study indicates that oxymatrine may prevent pulmonary hypertension
      through its antiproliferative, anti-inflammatory, and antioxidant effects, thus
      providing a promising pharmacological avenue for treating pulmonary hypertension.

PMID- 24440470
TI  - The prognostic significance of preoperative leukocytosis in epithelial ovarian
      carcinoma: a retrospective cohort study.
AB  - OBJECTIVE: Preoperative leukocytosis is known to be a negative prognostic factor
      for several gynecologic malignancies, but its relationship with epithelial
      ovarian carcinoma (EOC) is unknown. We sought to evaluate the prognostic
      implications of preoperative leukocytosis for women with EOC. METHODS: We
      retrospectively reviewed the medical records of patients who underwent primary
      debulking surgery and adjuvant platinum-based chemotherapy for EOC between
      January 1993 and October 2011. Associations between leukocytosis and recurrence
      free survival (RFS) and overall survival (OS) were determined by univariate
      analyses. Multivariate Cox proportional hazards regression was used to identify
      independent prognostic factors for RFS and OS. RESULTS: Of 155 women, 23 (14.8%)
      had leukocytosis and 132 (85.2%) did not have leukocytosis. RFS and OS were
      significantly shorter for women with leukocytosis than for women without
      leukocytosis (P=0.009 and P<0.0001, respectively). The mortality rate was also
      higher among women with leukocytosis (P<0.0001). Multivariate analysis revealed
      that preoperative leukocytosis (hazard ratio [HR]: 2.15; 95% confidence interval
      [CI]: 1.55-4.41; P=0.009), advanced stage (HR: 3.12; 95% CI: 1.44-6.75; P=0.004),
      and optimal cytoreduction (HR: 0.38; 95% CI: 0.14-0.70; P=0.031) were independent
      prognostic factors for RFS. Additionally, preoperative leukocytosis was
      independently associated with decreased OS (HR: 7.66; 95% CI: 2.78-21.16;
      P<0.0001). CONCLUSIONS: Among women with EOC, preoperative leukocytosis might be
      an independent prognostic factor for RFS and OS. A larger-scaled, prospective
      study is needed to verify these results.

PMID- 24440471
TI  - The development and evaluation of a community based model for cervical cancer
      screening based on self-sampling.
AB  - OBJECTIVE: To develop and implement a community based model for cervical cancer
      prevention that allows the communities to manage the screening and the healthcare
      system to focus resources on evaluation and management of the positives. METHODS:
      Using self-sampling and the concepts founded in Community Based Participatory
      Research (CBPR), we progressively developed a model to efficiently reach the
      women, especially rural communities; and collect the volume of samples needed to
      support high throughput centralized low cost per case processing. RESULTS: 8382
      eligible women, ages 35 to 59, in 130 rural communities participated. The
      screening was organized by the local government administration and conducted by
      the community leaders (CLs). The model used was progressively designed through
      detailed assessment of key elements at 6 decision points in 26 workshops that
      were used to train the CLs and the local promoters. The communities were able to
      accurately conduct the screening; in the final model a local medical worker
      conducted a 50-minute workshop featuring instructional posters and structured
      role-play. A manual and a workshop DVD were created for distribution to and
      implementation by local governments. The average callback rate was 84.3%, without
      involvement of the local doctors in the management of the positives. CONCLUSION:
      An efficient community based model capable of massive screening events was
      developed. We believe that the callback rate will be further improved when local
      doctors are trained in the management of the positives. Many elements impact
      coverage and further research is needed to define the influence of the identified
      key variables.

PMID- 24440472
TI  - Counterion-mediated cluster formation by polyphosphoinositides.
AB  - Polyphosphoinositides (PPI) and in particular PI(4,5)P2, are among the most
      highly charged molecules in cell membranes, are important in many cellular
      signaling pathways, and are frequently targeted by peripheral polybasic proteins
      for anchoring through electrostatic interactions. Such interactions between PIP2
      and proteins containing polybasic stretches depend on the physical state and the
      lateral distribution of PIP2 within the inner leaflet of the cell's lipid
      bilayer. The physical and chemical properties of PIP2 such as pH-dependent
      changes in headgroup ionization and area per molecule as determined by
      experiments together with molecular simulations that predict headgroup
      conformations at various ionization states have revealed the electrostatic
      properties and phase behavior of PIP2-containing membranes. This review focuses
      on recent experimental and computational developments in defining the physical
      chemistry of PIP2 and its interactions with counterions. Ca(2+)-induced changes
      in PIP2 charge, conformation, and lateral structure within the membrane are
      documented by numerous experimental and computational studies. A simplified
      electrostatic model successfully predicts the Ca(2+)-driven formation of PIP2
      clusters but cannot account for the different effects of Ca(2+) and Mg(2+) on
      PIP2-containing membranes. A more recent computational study is able to see the
      difference between Ca(2+) and Mg(2+) binding to PIP2 in the absence of a membrane
      and without cluster formation. Spectroscopic studies suggest that divalent cation
      and multivalent polyamine-induced changes in the PIP2 lateral distribution in
      model membrane are also different, and not simply related to the net charge of
      the counterion. Among these differences is the capacity of Ca(2+) but not other
      polycations to induce nm scale clusters of PIP2 in fluid membranes. Recent super
      resolution optical studies show that PIP2 forms nanoclusters in the inner leaflet
      of a plasma membrane with a similar size distribution as those induced by Ca(2+)
      in model membranes. The mechanisms by which PIP2 forms nanoclusters and other
      structures inside a cell remain to be determined, but the unique electrostatic
      properties of PIP2 and its interactions with multivalent counterions might have
      particular physiological relevance. 

PMID- 24440473
TI  - Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in
      rectal cancer: long-term results of the EORTC 22921 randomised study.
AB  - BACKGROUND: EORTC trial 22921 examined the addition of preoperative or
      postoperative chemotherapy to preoperative radiotherapy in patients with rectal
      cancer. After a median follow-up of 5 years, chemotherapy-irrespective of timing
      significantly improved local control. Adjuvant chemotherapy did not improve
      survival, but the Kaplan-Meier curves diverged, suggesting possible delayed
      benefit. Here, we report the updated long-term results. METHODS: We randomly
      assigned patients with clinical stage T3 or T4 resectable rectal cancer to
      receive preoperative radiotherapy with or without concomitant chemotherapy before
      surgery followed by either adjuvant chemotherapy or surveillance. Randomisation
      was done using minimisation with factors of institution, sex, T stage, and
      distance from the tumour to the anal verge. Study coordinators, clinicians, and
      patients were aware of assignment. Radiotherapy consisted of 45 Gy to the
      posterior pelvis in 25 fractions of 1.8 Gy over 5 weeks. Each course of
      chemotherapy consisted of fluorouracil (350 mg/m(2) per day intravenous bolus)
      and folinic acid (leucovorin; 20 mg/m(2) per day intravenous bolus). For
      preoperative chemotherapy, two courses were given (during weeks 1 and 5 of
      radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. The
      primary endpoint was overall survival. This analysis was done by intention to
      treat. The trial is registered with ClinicalTrials.gov, number NCT00002523.
      FINDINGS: 1011 patients were randomly assigned to treatment between April, 1993,
      and March, 2003 (252 to preoperative radiotherapy and 253 to each of the other
      three groups). After a median follow-up of 10.4 years (IQR 7.8-13.1), 10-year
      overall survival was 49.4% (95% CI 44.6-54.1) for the preoperative radiotherapy
      group and 50.7% (45.9-55.2) for the preoperative radiotherapy and chemotherapy
      group (HR 0.99, 95% CI 0.83-1.18; p=0.91). 10-year overall survival was 51.8%
      (95% CI 47.0-56.4) for the adjuvant chemotherapy group and 48.4% (43.6-53.0) for
      the surveillance group (HR 0.91, 95% CI 0.77-1.09, p=0.32). 10-year disease-free
      survival was 44.2% (95% CI 39.5-48.8) for the preoperative radiotherapy group and
      46.4% (41.7-50.9) for the preoperative radiotherapy and chemotherapy group (HR
      0.93, 95% CI 0.79-1.10; p=0.38). 10-year disease-free survival was 47.0% (95% CI
      42.2-51.6) for the adjuvant chemotherapy group and 43.7% (39.1-48.2) for the
      surveillance group (HR 0.91, 95% CI 0.77-1.08, p=0.29). At 10 years, cumulative
      incidence of local relapse was 22.4% (95% CI 17.1-27.6) with radiotherapy alone,
      11.8% (7.8-15.8) with neoadjuvant radiotherapy and chemotherapy, 14.5% (10.1
      18.9) with radiotherapy and adjuvant chemotherapy and 11.7% (7.7-15.6) with both
      adjuvant and neoadjuvant chemotherapy (p=0.0017). There was no difference in
      cumulative incidence of distant metastases (p=0.52). The frequency of long-term
      side-effects did not differ between the four groups (p=0.22). INTERPRETATION:
      Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy (with or
      without chemotherapy) does not affect disease-free survival or overall survival.
      Our trial does not support the current practice of adjuvant chemotherapy after
      preoperative radiotherapy with or without chemotherapy. New treatment strategies
      incorporating neoadjuvant chemotherapy are required. FUNDING: EORTC, US National
      Cancer Institute, Programme Hospitalier de Recherche Clinique, Ligue contre le
      Cancer Comite du Doubs.

PMID- 24440474
TI  - Incidence of complications other than urinary incontinence or erectile
      dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a
      population-based cohort study.
AB  - BACKGROUND: Studies of complications resulting from surgery or radiotherapy for
      prostate cancer have mainly focused on incontinence and erectile dysfunction. We
      aimed to assess other important complications associated with these treatments
      for prostate cancer. METHODS: We did a population-based retrospective cohort
      study, in which we used administrative hospital data, physician billing codes,
      and cancer registry data for men who underwent either surgery or radiotherapy
      alone for prostate cancer between 2002 and 2009 in Ontario, Canada. We measured
      the 5-year cumulative incidence of five treatment-related complication endpoints:
      hospital admissions; urological, rectal, or anal procedures; open surgical
      procedures; and secondary malignancies. FINDINGS: In the 32 465 patients included
      in the study, the 5-year cumulative incidence of admission to hospital for a
      treatment-related complication was 22.2% (95% CI 21.7-22.7), but was 2.4% (2.2
      2.6) for patients whose length of stay was longer than 1 day. The 5-year
      cumulative incidence of needing a urological procedure was 32.0% (95% CI 31.4
      32.5), that of a rectal or anal procedure was 13.7% (13.3-14.1), and that of an
      open surgical procedure was 0.9% (0.8-1.1). The 5-year cumulative incidence of a
      second primary malignancy was 3.0% (2.6-3.5). These risks were significantly
      higher than were those of 32 465 matched controls with no history of prostate
      cancer. Older age and comorbidity at the time of index treatment were important
      predictors for a complication in all outcome categories, but the type of
      treatment received was the strongest predictor for complications. Patients who
      were given radiotherapy had higher incidence of complications for hospital
      admissions, rectal or anal procedures, open surgical procedures, and secondary
      malignancies at 5 years than did those who underwent surgery (adjusted hazard
      ratios 2.08-10.8, p<0.0001). However, the number of urological procedures was
      lower in the radiotherapy than in the surgery group (adjusted hazard ratio 0.66,
      95% CI 0.63-0.69; p<0.0001) INTERPRETATION: Complications after prostate cancer
      treatment are frequent and dependent on age, comorbidity, and the type of
      treatment. Patients and physicians should be aware of these risks when choosing
      treatment for prostate cancer, and should balance them with the clinical
      effectiveness of each therapy. FUNDING: Ajmera Family Chair in Urologic Oncology.

PMID- 24440475
TI  - Complications from treatment of localised prostate cancer.

PMID- 24440476
TI  - Adjuvant chemotherapy for rectal cancer still controversial.

PMID- 24440477
TI  - Idiosyncrasies in decoding mitochondrial genomes.
AB  - Mitochondria originate from the alpha-proteobacterial domain of life. Since this
      unique event occurred, mitochondrial genomes of protozoans, fungi, plants and
      metazoans have highly derived and diverged away from the common ancestral DNA.
      These resulting genomes highly differ from one another, but all present-day
      mitochondrial DNAs have a very reduced coding capacity. Strikingly however, ATP
      production coupled to electron transport and translation of mitochondrial
      proteins are the two common functions retained in all mitochondrial DNAs.
      Paradoxically, most components essential for these two functions are now
      expressed from nuclear genes. Understanding how mitochondrial translation evolved
      in various eukaryotic models is essential to acquire new knowledge of
      mitochondrial genome expression. In this review, we provide a thorough analysis
      of the idiosyncrasies of mitochondrial translation as they occur between
      organisms. We address this by looking at mitochondrial codon usage and tRNA
      content. Then, we look at the aminoacyl-tRNA-forming enzymes in terms of
      peculiarities, dual origin, and alternate function(s). Finally we give examples
      of the atypical structural properties of mitochondrial tRNAs found in some
      organisms and the resulting adaptive tRNA-protein partnership. 

PMID- 24440478
TI  - Design, synthesis, and biological evaluation of a series of piperazine ureas as
      fatty acid amide hydrolase inhibitors.
AB  - A series of piperazine ureas were designed, synthesized, and evaluated for their
      potential as novel orally efficacious fatty acid amide hydrolase (FAAH)
      inhibitors for the treatment of neuropathic and inflammatory pain. We carried out
      an optimization study of compound 5 to improve its in vitro FAAH inhibitory
      activity, and identified the 2-pyrimidinylpiperazine derivative 21d with potent
      inhibitory activity, favorable DMPK profile and brain permeability. Compound 21d
      showed robust and dose-dependent analgesic efficacy in animal models of both
      neuropathic and inflammatory pain. 

PMID- 24440479
TI  - Discovery of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)-sulfonamide
      derivatives as novel protein kinase and angiogenesis inhibitors for the treatment
      of cancer: Synthesis and biological evaluation. Part III.
AB  - A novel series of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)
      sulfonamides were designed and synthesized. Biological characterization revealed
      that several compounds exerted enhanced anti-proliferative activity against human
      umbilical vein endothelial cells (HUVECs) and several cancer cell lines and high
      specific protein kinase and angiogenesis inhibitory activities. Compared with our
      previously synthesized compounds, the substitution of sulfonamide structure for
      amide fragment played an essential role for the advance of inhibitory activities.
      In addition, the replacement of 1H-1,2,4-triazole ring by 7H-purine did not
      result in obvious decrease of inhibition efficacy, indicating that the
      sulfonamide structure contributes even more to the inhibition efficacy than the
      1H-1,2,4-triazole ring. Among these compounds, compound 9n demonstrated
      comparable in vitro antiangiogenic activities to pazopanib in both HUVEC tube
      formation assay and the rat thoracic aorta rings (TARs) test. Meanwhile, compound
      9n was identified to inhibit Akt1 (IC50=1.73 MUM) and Abl tyrosine kinase
      (IC50=1.53 MUM) effectively.

PMID- 24440481
TI  - Synthesis of chlorophyll-amino acid conjugates as models for modification of
      proteins with chromo/fluorophores.
AB  - A chlorophyll-a derivative bonded directly with epoxide at the peripheral
      position of the chlorin pi-system was reacted with N-urethane and C-ester
      protected amino acids bearing an alcoholic or phenolic hydroxy group as well as a
      carboxy group at the residue to give chlorophyll-amino acid conjugates. The
      carboxy residues of N,C-protected aspartic and glutamic acids were esterified
      with the epoxide in high yields. The synthetic conjugates in dichloromethane had
      absorption bands throughout the visible region including intense red-side Qy and
      blue-side Soret bands. By their excitation at the visible bands, strong and
      efficient fluorescence emission was observed up to the near-infrared region. The
      chromo/fluorophores are promising for preparation of functional peptides and
      modification of proteins. 

PMID- 24440480
TI  - Insights into the mechanism of streptonigrin-induced protein arginine deiminase
      inactivation.
AB  - Protein citrullination is just one of more than 200 known PTMs. This
      modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in
      humans), converts the positively charged guanidinium group of an arginine residue
      into a neutral ureido-group. Given the strong links between dysregulated PAD
      activity and human disease, we initiated a program to develop PAD inhibitors as
      potential therapeutics for these and other diseases in which the PADs are thought
      to play a role. Streptonigrin which possesses both anti-tumor and anti-bacterial
      activity was later identified as a highly potent PAD4 inhibitor. In an effort to
      understand why streptonigrin is such a potent and selective PAD4 inhibitor, we
      explored its structure-activity relationships by examining the inhibitory effects
      of several analogues that mimic the A, B, C, and/or D rings of streptonigrin. We
      report the identification of the 7-amino-quinoline-5,8-dione core of
      streptonigrin as a highly potent pharmacophore that acts as a pan-PAD inhibitor. 

PMID- 24440484
TI  - Literature mining of protein phosphorylation using dependency parse trees.
AB  - As one of the most common post-translational modifications (PTMs), protein
      phosphorylation plays an important role in various biological processes, such as
      signaling transduction, cellular metabolism, differentiation, growth, regulation
      and apoptosis. Protein phosphorylation is of great value not only in illustrating
      the underlying molecular mechanisms but also in treatment of diseases and design
      of new drugs. Recently, there is an increasing interest in automatically
      extracting phosphorylation information from biomedical literatures. However, it
      still remains a challenging task due to the tremendous volume of literature and
      circuitous modes of expression for protein phosphorylation. To address this
      issue, we propose a novel text-mining method for efficiently retrieving and
      extracting protein phosphorylation information from literature. By employing
      natural language processing (NLP) technologies, this method transforms each
      sentence into dependency parse trees that can precisely reflect the intrinsic
      relationship of phosphorylation-related key words, from which detailed
      information of substrates, kinases and phosphorylation sites is extracted based
      on syntactic patterns. Compared with other existing approaches, the proposed
      method demonstrates significantly improved performance, suggesting it is a
      powerful bioinformatics approach to retrieving phosphorylation information from a
      large amount of literature. A web server for the proposed method is freely
      available at http://bioinformatics.ustc.edu.cn/pptm/. 

PMID- 24440482
TI  - Single molecule photobleaching (SMPB) technology for counting of RNA, DNA,
      protein and other molecules in nanoparticles and biological complexes by TIRF
      instrumentation.
AB  - Direct counting of biomolecules within biological complexes or nanomachines is
      demanding. Single molecule counting using optical microscopy is challenging due
      to the diffraction limit. The single molecule photobleaching (SMPB) technology
      for direct counting developed by our team (Shu et al., 2007 [18]; Zhang et al.,
      2007 [19]) offers a simple and straightforward method to determine the
      stoichiometry of molecules or subunits within biocomplexes or nanomachines at
      nanometer scales. Stoichiometry is determined by real-time observation of the
      number of descending steps resulted from the photobleaching of individual
      fluorophore. This technology has now been used extensively for single molecule
      counting of protein, RNA, and other macromolecules in a variety of complexes or
      nanostructures. Here, we elucidate the SMPB technology, using the counting of RNA
      molecules within a bacteriophage phi29 DNA-packaging biomotor as an example. The
      method described here can be applied to the single molecule counting of other
      molecules in other systems. The construction of a concise, simple and economical
      single molecule total internal reflection fluorescence (TIRF) microscope
      combining prism-type and objective-type TIRF is described. The imaging system
      contains a deep-cooled sensitive EMCCD camera with single fluorophore detection
      sensitivity, a laser combiner for simultaneous dual-color excitation, and a Dual
      ViewTM imager to split the multiple outcome signals to different detector
      channels based on their wavelengths. Methodology of the single molecule
      photobleaching assay used to elucidate the stoichiometry of RNA on phi29 DNA
      packaging motor and the mechanism of protein/RNA interaction are described.
      Different methods for single fluorophore labeling of RNA molecules are reviewed.
      The process of statistical modeling to reveal the true copy number of the
      biomolecules based on binomial distribution is also described. 

PMID- 24440483
TI  - Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the
      nanoparticle [Gd@C82(OH)22]n: A systems biology study.
AB  - The nanoparticle gadolinium endohedral metallofullerenol [Gd@C82(OH)22]n is a new
      candidate for cancer treatment with low toxicity. However, its anti-cancer
      mechanisms remain mostly unknown. In this study, we took a systems biology view
      of the gene expression profiles of human breast cancer cells (MCF-7) and human
      umbilical vein endothelial cells (ECV304) treated with and without
      [Gd@C82(OH)22]n, respectively, measured by the Agilent Gene Chip G4112F. To
      properly analyze these data, we modified a suit of statistical methods we
      developed. For the first time we applied the sub-sub normalization to Agilent two
      color microarrays. Instead of a simple linear regression, we proposed to use a
      one-knot SPLINE model in the sub-sub normalization to account for nonlinear
      spatial effects. The parameters estimated by least trimmed squares- and S
      estimators show similar normalization results. We made several kinds of
      inferences by integrating the expression profiles with the bioinformatic
      knowledge in KEGG pathways, Gene Ontology, JASPAR, and TRANSFAC. In the
      transcriptional inference, we proposed the BASE2.0 method to infer a
      transcription factor's up-regulation and down-regulation activities separately.
      Overall, [Gd@C82(OH)22]n induces more differentiation in MCF-7 cells than in
      ECV304 cells, particularly in the reduction of protein processing such as protein
      glucosylation, folding, targeting, exporting, and transporting. Among the KEGG
      pathways, the ErbB signaling pathway is up-regulated, whereas protein processing
      in endoplasmic reticulum (ER) is down-regulated. CHOP, a key pro-apoptotic gene
      downstream of the ER stress pathway, increases to nine folds in MCF-7 cells after
      treatment. These findings indicate that ER stress may be one important factor
      that induces apoptosis in MCF-7 cells after [Gd@C82(OH)22]n treatment. The
      expression profiles of genes associated with ER stress and apoptosis are
      statistically consistent with other profiles reported in the literature, such as
      those of HEK293T and MCF-7 cells induced by the miR-23a~27a~24-2 cluster.
      Furthermore, one of the inferred regulatory mechanisms comprises the apoptosis
      network centered around TP53, whose effective regulation of apoptosis is somehow
      reestablished after [Gd@C82(OH)22]n treatment. These results elucidate the
      application and development of [Gd@C82(OH)22]n and other fullerene derivates. 

PMID- 24440485
TI  - Variable criteria for patellofemoral bracing among sports medicine professionals.
AB  - OBJECTIVE: To examine whether the frequency of bracing, geographic region,
      clinical specialty, or percentage of practice devoted to knee pain influences the
      criteria used by sports medicine professionals to determine whether a brace
      should be prescribed for treating patients with nontraumatic patellofemoral pain
      syndrome. DESIGN: Cross-sectional study. SETTING: Sports medicine practices in
      the United States. PARTICIPANTS: A total of 1307 athletic trainers, physical
      therapists, and sports medicine physicians recruited from the e-mail listings of
      the American Medical Society for Sports Medicine, the American Osteopathic
      Academy of Sports Medicine, the American Physical Therapy Association Sports
      Physical Therapy Section, the International Patellofemoral Study Group, the
      International Patellofemoral Retreat list, and National Collegiate Athletic
      Association Division 1 athletic team registries. INTERVENTIONS: Not applicable.
      MAIN OUTCOMES MEASURES: Thirty-seven potential patellofemoral bracing criteria
      encompassing history and function, alignment, physical examination, previous
      treatments, and radiographic evidence. RESULTS: A total of 1307 of 7999 providers
      replied (response rate, 16.3%). Mean bracing frequencies were 19.8% for athletic
      trainers, 13.4% for physical therapists, and 25.1% for physicians. The mean
      number of total bracing criteria used was 10.5. The 10 most commonly cited
      criteria for prescribing a patellofemoral brace in descending order of frequency
      were: (1) hypermobile patella on physical examination; (2) positive J sign on
      physical examination; (3) failure of previous rehabilitation; (4) pain when
      performing squats or going up/down stairs on history; (5) success with previous
      taping; (6) pain with running activities on history; (7) pain with jumping
      activities on history; (8) increased dynamic Q angle; (9) vastus medialis oblique
      deficiency in timing or strength; and (10) positive apprehension sign on physical
      examination. No statistically significant trends were noted with regard to
      experience or percentage of practice devoted to knee pain. Increased bracing
      frequency was significantly associated with an increased number of bracing
      criteria (r = 0.89, P < .0001). CONCLUSIONS: This study identified little overall
      consensus and showed that significant differences exist in the criteria used to
      prescribe a brace for patellofemoral pain syndrome among specialties and in
      relation to bracing frequency.

PMID- 24440486
TI  - Effects of molecular weight of grafted hyaluronic acid on wear initiation.
AB  - Hyaluronic acid (HA) of different molecular weights (Mw) was grafted onto mica
      surfaces to study the effects of Mw on the conformation and wear protection
      properties of a grafted HA (gHA) layer in lubricin (LUB) and bovine synovial
      fluid (BSF) using a surface forces apparatus. The Mw of gHA had significant
      effects on the wear pressure (Pw), at which point the wear initiates. Increasing
      the gHA Mw from 51 to 2590kDa increased Pw from 4 to 8MPa in LUB and from 15 to
      31MPa in BSF. The 2590kDa gHA in BSF had the best wear protection (Pw~31MPa),
      even though it exhibited the highest friction coefficient (MU~0.35), indicating
      that a low MU does not necessarily result in good wear protection, as is often
      assumed. The normal force profile indicated that BSF confines the gHA structure,
      making it polymer brush-like, commonly considered as an excellent structure for
      boundary lubrication. 

PMID- 24440488
TI  - Sequencing and characterization of the anadromous steelhead (Oncorhynchus mykiss)
      transcriptome.
AB  - Identifying the traits that differ between hatchery and wild fish may allow for
      pragmatic changes to hatchery practice. To meet those ends, we sequenced,
      assembled, and characterized the anadromous steelhead (Oncorhynchus mykiss)
      transcriptome. Using the Illumina sequencing platform, we sequenced nearly
      41million 76-mer reads representing 3.1 Gbp of steelhead transcriptome. Upon
      final assembly, this sequence data yielded 86,402 transcript scaffolds, of which,
      66,530 (77%) displayed homology to proteins of the non-redundant NCBI database.
      Gene descriptions and gene ontology terms were used to annotate the transcriptome
      resulting in 4030 unique gene ontology (GO) annotations attributed to the
      assembled sequences. We also conducted a comparative analysis that identified
      homologous genes within four other fish species including zebrafish (Danio
      rerio), stickleback (Gasterosteus aculeatus), and two pufferfish species
      (Tetraodon nigroviridis and Takifugu rubripes). Comparing our steelhead reference
      assembly directly to the transcriptome for rainbow trout (the fresh water life
      history variant of the same species) revealed that while the steelhead and
      rainbow trout transcriptomes are complementary, the steelhead data will be useful
      for investigating questions related to anadromous (ocean-going) fishes. These
      sequence data and web tools provide a useful set of resources for salmonid
      researchers and the broader genomics community (available at
      http://salmon.cgrb.oregonstate.edu). 

PMID- 24440487
TI  - Pluripotent stem cell-derived hepatocyte-like cells.
AB  - Liver disease is an important clinical problem, impacting over 30 million
      Americans and over 600 million people worldwide. It is the 12th leading cause of
      death in the United States and the 16th worldwide. Due to a paucity of donor
      organs, several thousand Americans die yearly while waiting for liver
      transplantation. Unfortunately, alternative tissue sources such as fetal
      hepatocytes and hepatic cell lines are unreliable, difficult to reproduce, and do
      not fully recapitulate hepatocyte phenotype and functions. As a consequence,
      alternative cell sources that do not have these limitations have been sought.
      Human embryonic stem (hES) cell- and induced pluripotent stem (iPS) cell-derived
      hepatocyte-like cells may enable cell based therapeutics, the study of the
      mechanisms of human disease and human development, and provide a platform for
      screening the efficacy and toxicity of pharmaceuticals. iPS cells can be
      differentiated in a step-wise fashion with high efficiency and reproducibility
      into hepatocyte-like cells that exhibit morphologic and phenotypic
      characteristics of hepatocytes. In addition, iPS-derived hepatocyte-like cells
      (iHLCs) possess some functional hepatic activity as they secrete urea, alpha-1
      antitrypsin, and albumin. However, the combined phenotypic and functional traits
      exhibited by iHLCs resemble a relatively immature hepatic phenotype that more
      closely resembles that of fetal hepatocytes rather than adult hepatocytes.
      Specifically, iHLCs express fetal markers such as alpha-fetoprotein and lack key
      mature hepatocyte functions, as reflected by drastically reduced activity (~0.1%)
      of important detoxification enzymes (i.e. CYP2A6, CYP3A4). These key differences
      between iHLCs and primary adult human hepatocytes have limited the use of stem
      cells as a renewable source of functional adult hepatocytes for in vitro and in
      vivo applications. Unfortunately, the developmental pathways that control
      hepatocyte maturation from a fetal into an adult hepatocyte are poorly
      understood, which has hampered the field in its efforts to induce further
      maturation of iPS-derived hepatic lineage cells. This review analyzes recent
      developments in the derivation of hepatocyte-like cells, and proposes important
      points to consider and assays to perform during their characterization. In the
      future, we envision that iHLCs will be used as in vitro models of human disease,
      and in the longer term, provide an alternative cell source for drug testing and
      clinical therapy.

PMID- 24440489
TI  - Bioaccumulation of cadmium by growing Zygosaccharomyces rouxii and Saccharomyces
      cerevisiae.
AB  - Bioaccumulation via growing cells is a potential technique for heavy metal
      removal from food materials. The cadmium bioaccumulation characteristics by
      growing Zygosaccharomyces rouxii and Saccharomyces cerevisiae were investigated.
      Z. rouxii displayed powerful cadmium removal ability at low cadmium
      concentrations, which mainly depended on the intracellular cadmium
      bioaccumulation. The percentage of intracellular cadmium bioaccumulation of both
      yeasts obviously decreased with the increase of initial biomass and cadmium
      concentrations. Low pH and elevated concentrations of zinc and copper
      significantly decreased the intracellular cadmium bioaccumulation of both yeasts
      but improved the cadmium tolerance and the cell-surface cadmium bioaccumulation
      of Z. rouxii. Cadmium removal of Z. rouxii was improved by zinc and copper
      conditionally. Z. rouxii that possessed more powerful cadmium tolerance and
      removal ability at low pH and high concentration of competing ions can be
      developed into a potential cadmium removal agent using in complex food
      environment in future. 

PMID- 24440490
TI  - Enzymatic and metabolic activities of four anaerobic sludges and their impact on
      methane production from ensiled sorghum forage.
AB  - Biochemical methane potential (BMP) tests were run on ensiled sorghum forage
      using four inocula (urban, agricultural, mixture of agricultural and urban,
      granular) and differences on their metabolic and enzymatic activities were also
      discussed. Results indicate that no significant differences were observed in
      terms of BMP values (258+/-14NmLCH4g(-1)VS) with a slightly higher value when
      agricultural sludge was used as inoculum. Significant differences can be observed
      among different inocula, in terms of methane production rate. In particular the
      fastest biomethanization occurred when using the urban sludge (hydrolytic kinetic
      constant kh=0.146d(-1)) while the slowest one was obtained from the agricultural
      sludge (kh=0.049d(-1)). Interestingly, positive correlations between the overall
      enzymatic activities and methane production rates were observed for all sludges,
      showing that a high enzymatic activity may favour the hydrolysis of complex
      substrate and accelerate the methanization process of sorghum. 

PMID- 24440491
TI  - Combinations of nitrate, saponin, and sulfate additively reduce methane
      production by rumen cultures in vitro while not adversely affecting feed
      digestion, fermentation or microbial communities.
AB  - This study investigated the effects of saponin (0.6g/L), nitrate (5mM) and
      sulfate (5mM), alone and in combinations, on methanogenesis, rumen fermentation,
      microbial community, and abundances of select microbial populations using in
      vitro rumen culture. Combinations of nitrate with saponin and/or sulfate
      additively suppressed methane production, with the lowest reduction (nearly 46%)
      observed for the combination of all the three inhibitors. None of the treatments
      adversely affected feed digestion or rumen fermentation. All the inhibitors,
      either alone or in combinations, did not alter the abundances of total bacteria,
      Ruminococcus albus, or archaea. However, saponin, alone and together with nitrate
      and/or sulfate, increased the abundance of Fibrobacter succinogenes and
      Ruminococcus flavefaciens, but decreased that of protozoa. DGGE analyses revealed
      limited changes in both bacterial and archaeal communities by the treatments. The
      nitrate-saponin-sulfate combination may be an effective and practical strategy to
      mitigate methane emission from ruminants. 

PMID- 24440492
TI  - Identification of occult breast lesions detected by magnetic resonance imaging
      with targeted ultrasound: a prospective study.
AB  - OBJECTIVE: To verify the capacity of targeted ultrasound (US) to identify
      additional lesions detected on breast magnetic resonance imaging (MRI), but
      occult to initial mammography, US and clinical examinations. METHODS: This
      prospective study included 68 additional relevant breast lesions identified on
      MRI of 49 patients. As an inclusion criterion, breast US and mammography were
      required and performed up to six months before MRI. These lesions were then
      subjected to targeted "second-look" US up to 2 weeks after MRI, performed by one
      or two radiologists with expertise on breast imaging. Lesions were evaluated
      according to the established Breast Imaging Report and Data System (BI-RADS)
      lexicon. RESULTS: Targeted US identified 46/68 (67.6%) lesions revealed by MRI.
      No significant associations were observed between US identification and the type
      of lesion, dimensions, morphological characteristics and enhancement pattern
      according to MRI findings. Targeted US identified 100% of BI-RADS category 5
      lesions, 90% of category 4 lesions, and just over 50% of category 3 lesions
      (p<0.05). There was significant agreement (p<0.001) between MRI and US BI-RADS
      classification for all three categories. CONCLUSION: Targeted US can identify a
      large proportion of the lesions detected by breast MRI, especially those at high
      risk of malignancy, when performed by a professional with experience in both
      breast US and MRI.

PMID- 24440493
TI  - Population health intervention research: developing a much needed science of
      solutions.

PMID- 24440494
TI  - Population impact of familial and environmental risk factors for schizophrenia: a
      nationwide study.
AB  - Although several studies have examined the relative contributions of familial and
      environmental risk factors for schizophrenia, few have additionally examined the
      predictive power on the individual level and simultaneously examined the
      population impact associated with a wide range of familial and environmental risk
      factors. The authors present rate ratios (IRR), population-attributable risks
      (PAR) and sex-specific cumulative incidences of the following risk factors:
      parental history of mental illness, urban place of birth, advanced paternal age,
      parental loss and immigration status. We established a population-based cohort of
      2,486,646million persons born in Denmark between 1 January 1955 and 31 December
      1993 using Danish registers. We found that PAR associated with urban birth was
      11.73%; PAR associated with one, respectively 2, parent(s) with schizophrenia was
      2.67% and 0.12%. PAR associated with second-generation immigration was 0.70%.
      Highest cumulative incidence (CI=20.23%; 95% CI=18.10-22.62) was found in male
      offspring of 2 parents with schizophrenia. Cumulative incidences for male
      offspring or female offspring of a parent with schizophrenia were 9.53% (95%
      CI=7.71-11.79), and 4.89%, (95% CI 4.50-5.31). The study showed that risk factors
      with highest predictive power on the individual level have a relatively low
      population impact. The challenge in future studies with direct genetic data is to
      examine gene-environmental interactions that can move research beyond current
      approaches and seek to achieve higher predictive power on the individual level
      and higher population impact. 

PMID- 24440495
TI  - Evidence that treatment prevents transition to psychosis in ultra-high-risk
      patients remains questionable.

PMID- 24440496
TI  - Response to the letters of Dr Amos and Dr Preti and colleagues.

PMID- 24440497
TI  - IgG4 related disease of the ureter (inflammatory pseudotumor).

PMID- 24440499
TI  - Activation of TOPK by lipopolysaccharide promotes induction of inducible nitric
      oxide synthase through NF-kappaB activity in leukemia cells.
AB  - T-LAK cell-originated protein kinase (TOPK) is known to be involved in
      tumorigenesis or cancer progression. However, the role of TOPK in inflammatory
      response remains elusive. Here we show that TOPK positively regulates inducible
      nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in
      response to lipopolysaccharide (LPS). In TOPK-depleted cells, the iNOS expression
      was shown to be greatly abolished. Also, we revealed that LPS treatment augmented
      the expression and activity of TOPK, the interaction of TOPK with IkappaBalpha,
      and promoted TOPK kinase activity against IkappaBalpha. Moreover, NF-kappaB or
      iNOS promoter-driven transcriptional activity in response to LPS was markedly
      reduced by knocking down of TOPK or deletion of NF-kappaB sites. On the other
      hand, endogenous TOPK level was expressed very lowly in bone marrow-derived
      macrophage (BMDM) prepared from Toll-like receptor 4 (TLR4) knockout mice,
      compared to BMDM from wild type (WT) mice. Collectively, these findings
      demonstrate that TOPK upregulates iNOS gene expression in T cell leukemia Jurkat
      cells or macrophage leukemic Raw 264.7 cells via NF-kappaB activation in response
      to LPS, and might act as a critical effector in LPS/TLR4-mediated signaling
      cascade, suggesting a possible role of TOPK in inflammatory response or
      inflammation-related diseases. 

PMID- 24440500
TI  - Serum calprotectin levels in elderly males and females without bacterial or viral
      infections.
AB  - OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin
      can thus be used as a marker for leukocyte activation. Faeces calprotectin is not
      only used as a marker for inflammatory bowel disease but can also be used to
      detect leukocyte activation in other body fluids. The aim of the present study
      was to study serum calprotectin levels in non-infected elderly individuals to
      establish reference intervals for the marker. METHODS: Serum calprotectin was
      analyzed by immunoturbidimetry in 75 year old females and males without known
      infections. Individuals with CRP>20mg/L were excluded as this could indicate a
      subclinical infection. The calprotectin levels in the remaining 713 individuals
      were used to calculate reference values for this population. The Spearman rank
      correlations between calprotectin and 27 other laboratory biomarkers were also
      investigated. RESULTS: There was a strong positive Spearman rank correlation
      between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001).
      There were also significant negative correlations between calprotectin and ApoA1
      and direct HDL-cholesterol. CONCLUSIONS: The reference interval for serum
      calprotectin for all study subjects was 0.3-2.6 mg/L. Leukocyte alkaline
      phosphatase contributes to serum alkaline phosphatase levels.

PMID- 24440501
TI  - Introduction to special issue for biobanks and biorepositories.

PMID- 24440502
TI  - Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1
      kinase.
AB  - Bulk degradation of cytoplasmic material is mediated by a highly conserved
      intracellular trafficking pathway termed autophagy. This pathway is characterized
      by the formation of double-membrane vesicles termed autophagosomes engulfing the
      substrate and transporting it to the vacuole/lysosome for breakdown and
      recycling. The Atg1/ULK1 kinase is essential for this process; however, little is
      known about its targets and the means by which it controls autophagy. Here we
      have screened for Atg1 kinase substrates using consensus peptide arrays and
      identified three components of the autophagy machinery. The multimembrane
      spanning protein Atg9 is a direct target of this kinase essential for autophagy.
      Phosphorylated Atg9 is then required for the efficient recruitment of Atg8 and
      Atg18 to the site of autophagosome formation and subsequent expansion of the
      isolation membrane, a prerequisite for a functioning autophagy pathway. These
      findings show that the Atg1 kinase acts early in autophagy by regulating the
      outgrowth of autophagosomal membranes.

PMID- 24440503
TI  - A feedforward regulatory loop between HuR and the long noncoding RNA linc-MD1
      controls early phases of myogenesis.
AB  - The muscle-specific long noncoding RNA linc-MD1 was shown to be expressed during
      early phases of muscle differentiation and to trigger the switch to later stages
      by acting as a sponge for miR-133 and miR-135. Notably, linc-MD1 is also the host
      transcript of miR-133b, and their biogenesis is mutually exclusive. Here, we
      describe that this alternative synthesis is controlled by the HuR protein, which
      favors linc-MD1 accumulation through its ability to bind linc-MD1 and repress
      Drosha cleavage. We show that HuR is under the repressive control of miR-133 and
      that the sponging activity of linc-MD1 consolidates HuR expression in a
      feedforward positive loop. Finally, we show that HuR also acts in the cytoplasm,
      reinforcing linc-MD1 sponge activity by cooperating for miRNA recruitment. An
      increase in miR-133 synthesis, mainly from the two unrelated miR-133a coding
      genomic loci, is likely to trigger the exit from this circuitry and progression
      to later differentiation stages.

PMID- 24440504
TI  - Extensive oscillatory gene expression during C. elegans larval development.
AB  - Oscillations are a key to achieving dynamic behavior and thus occur in biological
      systems as diverse as the beating heart, defecating worms, and nascent somites.
      Here we report pervasive, large-amplitude, and phase-locked oscillations of gene
      expression in developing C. elegans larvae, caused by periodic transcription.
      Nearly one fifth of detectably expressed transcripts oscillate with an 8 hr
      period, and hundreds change >10-fold. Oscillations are important for molting but
      occur in all phases, implying additional functions. Ribosome profiling reveals
      that periodic mRNA accumulation causes rhythmic translation, potentially
      facilitating transient protein accumulation as well as coordinated production of
      stable, complex structures such as the cuticle. Finally, large-amplitude
      oscillations in RNA sampled from whole worms indicate robust synchronization of
      gene expression programs across cells and tissues, suggesting that these
      oscillations will be a powerful new model to study coordinated gene expression in
      an animal.

PMID- 24440505
TI  - Work related injuries in Washington State's Trucking Industry, by industry sector
      and occupation.
AB  - BACKGROUND: The trucking industry continues to have some of the highest work
      related injury and illness rates and costs of any industry in the United States.
      Until recently, little focus has been placed on addressing non-motor vehicle
      collision related injuries within the trucking industry. Drivers are exposed to
      multiple physical risk factors that contribute to occupational injuries in order
      to complete their job duties, such as loading/unloading freight, decoupling
      trailers, strapping down loads and ingress and egress from the cab and trailer.
      About one-fourth of all truck driver injuries in the United States are related to
      slips, trips, and falls near the truck. PURPOSE: The purpose of this descriptive
      study is to report on recent injuries in the trucking industry in Washington
      State. Data are presented by occupation and industry sector, in order to better
      understand the magnitude of specific injuries in terms of time-loss days and
      workers' compensation costs. METHODS: All accepted, compensable (time-loss)
      claims from 2005 to 2010 within the trucking industry in Washington State were
      reviewed. Counts, rates, median and quartile data are presented. Logistic
      regression models are presented to identify factors associated with more severe
      claims. RESULTS: Non-traumatic musculoskeletal disorders of the neck, back and
      upper extremities are the most frequent injuries across all industry sectors and
      occupations in the trucking industry. Vehicle related claims had the highest
      median costs and time loss days and Courier and Messenger claims had the highest
      risk for higher time loss claims. Injuries varied substantially by sector and
      within sectors by occupation. CONCLUSION: It is important to review work-related
      injuries within the trucking industry by sector and occupation in order to
      maximize limited resources for injury prevention within this important sector.

PMID- 24440506
TI  - Expression of soluble recombinant lipoxygenase from Pleurotus sapidus in Pichia
      pastoris.
AB  - The first heterologous expression of an iron-containing lipoxygenase from a
      basidiomycete in Pichia pastoris is reported. Five different expression
      constructs of the lipoxygenase gene LOX1 from Pleurotus sapidus were cloned and
      successfully transferred into P. pastoris SMD1168, but only one pPIC9K vector
      construct was functionally expressed. In this construct the vector-provided alpha
      factor signal sequence was replaced by insertion of a second Kozak sequence
      between the signal sequence and the LOX1 gene. His(+) transformants were screened
      for their level of resistance to geneticin (G418). Lox1 was expressed under
      different culture conditions and purified using the N-terminal His-tag. Relative
      enzyme activity increased significantly 48h after methanol induction and was
      highest with 2mll(-1) inducer. The recombinant enzyme showed an optimal
      lipoxygenase activity at pH 7 and 30-35 degrees C and a vmax like the wild-type
      enzyme. 

PMID- 24440507
TI  - Negative tail fusions can improve ruggedness of single domain antibodies.
AB  - Single-domain antibodies (sdAbs), the recombinantly expressed binding domains
      derived from the heavy-chain-only antibodies found in camelids and sharks, are
      valued for their ability to refold after heat denaturation. However, some sdAbs
      are prone to aggregation on extended heating at high concentration. Additionally,
      sdAbs prepared cytoplasmically often lack the conserved disulfide bond found in
      variable heavy domains, which both decreases their melting point and can decrease
      their ability to refold. Genetic fusions of sdAbs with the acid tail of alpha
      synuclein (ATS) resulted in constructs that had enhanced ability to resist
      aggregation. In addition, almost complete refolding was observed even in the
      absence of the disulfide bond. These sdAb-ATS fusions expand the utility of
      sdAbs. They provide sdAbs that are resistant to aggregation, and enable the
      production of re-foldable sdAbs in the reducing environment of the cytoplasm. 

PMID- 24440508
TI  - A dynamic dosimetry model for radioactive exposure scenarios in Arabidopsis
      thaliana.
AB  - To obtain a better understanding on how non-human biota are affected by exposure
      to environmental radioactivity, it is essential to link observed effects to a
      correct estimate of absorbed ionising radiation dose. Current wildlife dose rate
      and risk assessment tools are not set up to assess changes in dose rate during
      organism development. This paper presents a dosimetry model for assessing dose
      rate and absorbed dose during seedling development of the model plant Arabidopsis
      thaliana. We included growth and radionuclide absorption dynamics into the dose
      calculations. This model was subsequently used to compare the dose and dose rate
      calculations for three radionuclides, (241)Am (alpha-radiation), (90)Sr (beta
      radiation) and (133)Ba (gamma-radiation), in a standard exposure scenario. We
      show that growth influences dose and dose rate and that this influence depends on
      the radionuclide and the organ involved. The use of dynamic dosimetry models
      greatly improves the dose calculations for effect studies. 

PMID- 24440510
TI  - Editorial comment.

PMID- 24440509
TI  - Resistance surveillance program report for selected European nations (2011).
AB  - In the European component of the Regional Resistance Surveillance study for 2011,
      a total of 21 countries were monitored for antimicrobial resistance patterns
      including Belgium, Bulgaria (BU), Croatia, Czech Republic, France (F), Germany
      (GE), Greece (GR), Ireland (IR), Israel (IS), Italy (IT), Poland (PO), Portugal
      (PT), Romania (RO), Russia (RU), Slovakia (SK), Slovenia, Spain, Sweden (SW),
      Turkey (T), Ukraine, and United Kingdom. Results from testing 12,572 strains (100
      [BU] to 1535 [F] per nation) were interpreted by contemporary published
      breakpoints. Samples from 47 hospitals were reference tested against agents such
      as amikacin (AMK), cefoperazone/sulbactam (C/S), colistin (COL), levofloxacin,
      linezolid (LZD), tigecycline (TIG), vancomycin (VAN), and 21 others. Among
      Staphylococcus aureus, LZD (MIC90, 2 MUg/mL), TIG (MIC90, 0.12 MUg/mL), and VAN
      (MIC90, 1 MUg/mL) exhibited complete coverage and methicillin resistance rates
      among nations (average, 31%) ranged from 0.9% (SW) to 60.0-60.2% (PT, SK). Seven
      LZD-resistant coagulase-negative staphylococci (only 1.1% resistance overall)
      were noted in 5 nations, and a Staphylococcus simulans strain (MIC, 8 MUg/mL from
      RO) had L3 mutations (N130D, G152A, F147S, A157R); also 6 LZD-resistant
      enterococci were detected in 3 countries (GE, IR, T). VAN-resistant enterococci
      (10% overall; 84% VanA) were found in 14 countries, highest in GE and IR (23.0%).
      The ESBL phenotype rate for Escherichia coli was 20.1% (range, 0.9% [SW] to 70.0
      89.7% [BU, RU]), best inhibited by COL (100.0% S), TIG (100.0%), AMK (83.3
      94.1%), C/S (81.0%), and carbapenems (>99.0%; resistant strains in IS and T).
      Klebsiella spp. had greater ESBL rates (45.7% overall, range 2.5-100.0%), as well
      as carbapenem resistance (8.3% overall, greatest in BU, GR, IS, IT, PO, RO, RU,
      T). Non-fermentative Gram-negative bacilli (Pseudomonas aeruginosa, Acinetobacter
      [ACB]) were generally less susceptible, except against COL (99.2-99.6% S) and TIG
      (95.0% inhibited at <=2 MUg/mL; ACB only). The following carbapenemases were
      detected: VIM-1 (2 countries); IMP-1 (1 from T); KPC-2 or -3 (2 countries); VIM-4
      (1 from PO), NDM-1 (2 in RO; 2 centers); and OXA-48 or -162 (5 from T; 2
      centers). European surveillance sampling demonstrates a wide array of resistant
      isolates, less prevalent among Gram-positive cocci that remain inhibited by
      several available agents. However, beta-lactamase-mediated mechanisms have spread
      widely among Gram-negative bacilli, especially across the Eastern and Southern
      European nations, severely limiting infection chemotherapy and necessitating
      escalated antimicrobial stewardship. 

PMID- 24440513
TI  - Changes in amplitude-integrated electroencephalograms in piglets during selective
      mild head cooling after hypoxia-ischemia.
AB  - BACKGROUND: Amplitude-integrated electroencephalogram (aEEG) is a simplified,
      alternative means of monitoring cerebral function and may be more useful
      clinically in some situations than conventional EEG. The aim of this study is to
      evaluate newborn piglets as an animal model to examine the effect of selective
      mild head cooling (HC) on aEEG after hypoxia-ischemia (HI). METHODS: Thirty-four
      piglets were randomly allocated to the following treatment groups: normothermic
      control group (NC, n = 7), selective HC control group (HC, n = 9), normothermic
      HI group (NHI, n = 9), and selective HC HI group (SHC-HI, n = 9). HI was induced
      by temporary occlusion of both carotid arteries and simultaneous reduction of the
      concentration of inspired oxygen to 6% for 30 minutes. Mild hypothermia (35
      degrees C) was induced after HI using a HC cap and was maintained for 24 hours.
      Changes in aEEG were monitored for 6 days after these treatments and the
      incidence of abnormalities analyzed. Physiological parameters were also measured
      during this period. RESULTS: In the two HI groups, animals exhibited severely
      abnormal aEEGs [continuous low voltage (CLV), burst-suppression, or flat tracing
      (FT)] 20 minutes after the beginning of HI. At 2 hours, the aEEG returned to
      normal in most of these animals. From 12 hours to 6 days, all animals in the NHI
      group exhibited severely abnormal aEEGs. Fewer animals in the SHC-HI group
      exhibited severe abnormal aEEGs during this time period, and four out of nine
      (44.4%) animals had continuous normal voltage (CNV) at 6 days. CONCLUSIONS:
      Selective mild HC decreases the incidence of severe abnormal aEEGs at late times
      after HI in newborn piglets.

PMID- 24440514
TI  - Bone embrittlement and collagen modifications due to high-dose gamma-irradiation
      sterilization.
AB  - Bone allografts are often used in orthopedic reconstruction of skeletal defects
      resulting from trauma, bone cancer or revision of joint arthroplasty. gamma
      Irradiation sterilization is a widely-used biological safety measure; however it
      is known to embrittle bone. Irradiation has been shown to affect the post-yield
      properties, which are attributed to the collagen component of bone. In order to
      find a solution to the loss of toughness in irradiated bone allografts, it is
      important to fully understand the effects of irradiation on bone collagen. The
      objective of this study was to evaluate changes in the structure and integrity of
      bone collagen as a result of gamma-irradiation, with the hypothesis that
      irradiation fragments collagen molecules leading to a loss of collagen network
      connectivity and therefore loss of toughness. Using cortical bone from bovine
      tibiae, sample beams irradiated at 33kGy on dry ice were compared to native bone
      beams (paired controls). All beams were subjected to three-point bend testing to
      failure followed by characterization of the decalcified bone collagen, using
      differential scanning calorimetry (DSC), hydrothermal isometric tension testing
      (HIT), high performance liquid chromatography (HPLC) and gel electrophoresis (SDS
      PAGE). The carbonyl content of demineralized bone collagen was also measured
      chemically to assess oxidative damage. Barium sulfate staining after single edge
      notch bending (SEN(B)) fracture testing was also performed on bovine tibia bone
      beams with a machined and sharpened notch to evaluate the fracture toughness and
      ability of irradiated bone to form micro-damage during fracture. Irradiation
      resulted in a 62% loss of work-to-fracture (p<=0.001). There was significantly
      less micro-damage formed during fracture propagation in the irradiated bone. HPLC
      showed no significant effect on pentosidine, pyridinoline, or hydroxypyridinoline
      levels suggesting that the loss of toughness is not due to changes in these
      stable crosslinks. For DSC, there was a 20% decrease in thermal stability
      (p<0.001) with a 100% increase (p<0.001) in enthalpy of denaturation (melting).
      HIT testing also showed a decrease in thermal stability (20% lower denaturation
      temperature, p<0.001) and greatly reduced measures of collagen network
      connectivity (p<0.001). Interestingly, the increase in enthalpy of denaturation
      suggests that irradiated collagen requires more energy to denature (melt),
      perhaps a result of alterations in the hydrogen bonding sites (increased carbonyl
      content detected in the insoluble collagen) on the irradiated bone collagen.
      Altogether, this new data strongly indicates that a large loss of overall
      collagen connectivity due to collagen fragmentation resulting from gamma
      irradiation sterilization leads to inferior cortical bone toughness. In addition,
      notable changes in the thermal denaturation of the bone collagen along with
      chemical indicators of oxidative modification of the bone collagen indicate that
      the embrittlement may be a function not only of collagen fragmentation but also
      of changes in bonding. 

PMID- 24440515
TI  - Hepatic lipase is expressed by osteoblasts and modulates bone remodeling in
      obesity.
AB  - A number of unexpected molecules were recently identified as products of
      osteoblasts, linking bone homeostasis to systemic energy metabolism. Here we
      identify the lipolytic enzyme hepatic lipase (HL, encoded by Lipc) as a novel
      cell-autonomous regulator of osteoblast function. In an unbiased genome-wide
      expression analysis, we find Lipc to be highly induced upon osteoblast
      differentiation, verified by quantitative Taqman analyses of primary osteoblasts
      in vitro and of bone samples in vivo. Functionally, loss of HL in vitro leads to
      increased expression and secretion of osteoprotegerin (OPG), while expression of
      some osteoblast differentiation makers is impaired. When challenging energy
      metabolism in a diet-induced obesity (DIO) study, lack of HL leads to a
      significant increase in bone formation markers and a decrease in bone resorption
      markers. Accordingly, in the DIO setting, we observe in Lipc(-/-) animals but not
      in wild-type controls a significant increase in lumbar vertebral trabecular bone
      mass and formation rate as well as in femoral trabecular bone mass and cortical
      thickness. Taken together, we demonstrate that HL expressed by osteoblasts has an
      impact on osteoblast OPG expression and that lack of HL leads to increased bone
      mass in DIO. These data provide a novel and completely unexpected molecular link
      in the complex interplay of osteoblasts and systemic energy metabolism. 

PMID- 24440516
TI  - Determination of chitinases family during osteoclastogenesis.
AB  - Mammalian chitinases consisting of CHIA, CHIT1, CHI3L1, CHI3L2 and CHID1 exert
      important biological roles in the monocyte lineage and chronic inflammatory
      diseases. Pathological bone resorption is a cause of significant morbidity in
      diseases affecting the skeleton such as rheumatoid arthritis, osteoporosis,
      periodontitis and cancer metastasis. The biologic role of chitinases in bone
      resorption is poorly understood. In this study, we evaluated the expression of
      the chitinases family during osteoclast differentiation. The expression of CHIA,
      CHI3L2 and CHID1 resulted unchanged during osteoclast differentiation, whereas
      CHIT1 and CHI3L1 increased significantly. We also observed that CHIT1 and CHI3L1
      are involved in osteoclast function. Indeed, silencing CHIT1 and CHI3L1 with
      siRNA resulted in a significant decrease in bone resorption activity. In
      addition, transfection with CHIT1 or CHI3L1 siRNA and co-transfection with both
      decreased the levels of the pro-differentiative marker MMP9. Overall, these
      discoveries reveal a novel and crucial role for both CHIT1 and CHI3L1 in
      promoting bone resorption and identifying new potential candidate markers for
      therapeutic targeting. 

PMID- 24440517
TI  - Structure of the DNA-binding and RNA-polymerase-binding region of transcription
      antitermination factor lambdaQ.
AB  - The bacteriophage lambda Q protein is a transcription antitermination factor that
      controls expression of the phage late genes as a stable component of the
      transcription elongation complex. To join the elongation complex, lambdaQ binds a
      specific DNA sequence element and interacts with RNA polymerase that is paused
      during early elongation. lambdaQ binds to the paused early-elongation complex
      through interactions between lambdaQ and two regions of RNA polymerase: region 4
      of the sigma(70) subunit and the flap region of the beta subunit. We present the
      2.1 A resolution crystal structure of a portion of lambdaQ containing
      determinants for interaction with DNA, interaction with region 4 of sigma(70),
      and interaction with the beta flap. The structure provides a framework for
      interpreting prior genetic and biochemical analysis and sets the stage for future
      structural studies to elucidate the mechanism by which lambdaQ alters the
      functional properties of the transcription elongation complex. 

PMID- 24440518
TI  - Coiled-coil helix rotation selects repressing or activating state of
      transcriptional regulator DhaR.
AB  - Escherichia coli dihydroxyacetone (Dha) kinase consists of two subunits, DhaK and
      DhaL. Transcription of dha operon is regulated by the DhaR transcription factor
      and its action is under control of the kinase subunits. DhaR is activated by
      interaction with DhaL while it is repressed by DhaK. We have determined the
      structures of DhaK and DhaL bound to the tandem GAF-like and PAS domains of the
      DhaR, providing an architectural model for how GAF/PAS tandem domains work
      together in binding protein partners. The structures reveal a mechanism of
      opposite transcriptional regulation by the DhaK and DhaL subunits. The kinase
      subunits interface with DhaR through surfaces that partially overlap with their
      active sites, allowing sensing of ATP- versus ADP-loaded DhaL subunit and also
      precluding a ternary complex between DhaK-DhaL and DhaR. The rotation of helices
      within the DhaR coiled-coil linker upon DhaL binding provides the mechanism for
      transmitting the binding signal from the GAF/PAS domains to the C-terminal DNA
      binding domain.

PMID- 24440519
TI  - Non-model organisms, a species endangered by proteogenomics.
AB  - Previously, large-scale proteomics was possible only for organisms whose genomes
      were sequenced, meaning the most common model organisms. The use of next
      generation sequencers is now changing the deal. With "proteogenomics", the use of
      experimental proteomics data to refine genome annotations, a higher integration
      of omics data is gaining ground. By extension, combining genomic and proteomic
      data is becoming routine in many research projects. "Proteogenomic"-flavored
      approaches are currently expanding, enabling the molecular studies of non-model
      organisms at an unprecedented depth. Today draft genomes can be obtained using
      next-generation sequencers in a rather straightforward way and at a reasonable
      cost for any organism. Unfinished genome sequences can be used to interpret
      tandem mass spectrometry proteomics data without the need for time-consuming
      genome annotation, and the use of RNA-seq to establish nucleotide sequences that
      are directly translated into protein sequences appears promising. There are,
      however, certain drawbacks that deserve further attention for RNA-seq to become
      more efficient. Here, we discuss the opportunities of working with non-model
      organisms, the proteomic methods that have been used until now, and the dramatic
      improvements proffered by proteogenomics. These put the distinction between model
      and non-model organisms in great danger, at least in terms of proteomics!
      BIOLOGICAL SIGNIFICANCE: Model organisms have been crucial for in-depth analysis
      of cellular and molecular processes of life. Focusing the efforts of thousands of
      researchers on the Escherichia coli bacterium, Saccharomyces cerevisiae yeast,
      Arabidopsis thaliana plant, Danio rerio fish and other models for which genetic
      manipulation was possible was certainly worthwhile in terms of fundamental and
      invaluable biological insights. Until recently, proteomics of non-model organisms
      was limited to tedious, homology-based techniques, but today draft genomes or RNA
      seq data can be straightforwardly obtained using next-generation sequencers,
      allowing the establishment of a draft protein database for any organism. Thus,
      proteogenomics opens new perspectives for molecular studies of non-model
      organisms, although they are still difficult experimental organisms. This article
      is part of a Special Issue entitled: Proteomics of non-model organisms.

PMID- 24440520
TI  - The anti-apoptotic gene Anamorsin is essential for both autonomous and extrinsic
      regulation of murine fetal liver hematopoiesis.
AB  - Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent
      survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal
      because of a defect in definitive hematopoiesis; however, the significance of AM
      in embryonic hematopoiesis remains unknown. This study characterized the
      hematopoietic defects in AM(-/-) fetal livers. The AM(-/-) fetal liver displayed
      significantly reduced numbers of c-Kit(+)Sca-1(+)Lin(-) (KSL) cells. An in vitro
      colony-forming unit assay showed that fetal liver cells isolated from AM(-/-)
      embryos gave rise to fewer colonies in all cell types. The reconstitution
      activity in AM(-/-) hematopoietic stem cells (HSCs) was markedly reduced in all
      lineages. Furthermore, the limiting dilution assay revealed that the number of
      fetal liver HSCs was reduced because of AM deficiency. Retrovirus-mediated AM
      expression rescued the defective hematopoietic colony-forming activities of AM(-/
      ) KSL cells. We also investigated the effects of AM deficiency on fetal liver
      stromal cells, which support hematopoiesis. Interestingly, primary stromal cell
      cultures from wild type fetal liver supported the growth of AM(-/-) KSL cells,
      but stromal cultures from AM(-/-) fetal liver provided little support of wild
      type KSL cell growth. These results demonstrated that AM was essential for both
      autonomous and extrinsic regulation of fetal liver hematopoiesis. This study
      provided new insight into the molecular regulation of hematopoiesis.

PMID- 24440521
TI  - Indirect immune recognition of mouse embryonic stem cell-derived hematopoietic
      progenitors in vitro.
AB  - The clinical use of embryonic stem cell (ESC)-derived hematopoietic progenitors
      (ESHPs) requires the generation of ESHPs that produce mature hematopoietic cells
      and do not induce immune rejection after transplantation. We compared the
      developmental maturity and immunogenicity of ESHPs generated using two methods:
      embryoid body (EB) formation and culture of ESCs with the OP9 bone marrow stromal
      cell line (ESC-OP9). ESHPs derived from EBs displayed an immature hematopoietic
      phenotype and were devoid of immunogenicity marker expression. In contrast, ESHPs
      derived via ESC-OP9 displayed a mature phenotype and expressed high levels of
      some immunostimulatory molecules. ESHPs alone could not stimulate CD4(+) T
      lymphocyte proliferation directly. However, preferential phagocytosis of ESHPs
      and T cell proliferation were observed in the presence of antigen-presenting
      cells, consistent with a model of indirect immune recognition of ESHPs. These
      results suggest that depletion of host CD4(+) T lymphocytes or antigen-presenting
      cells may be necessary for successful ESHP transplantation. 

PMID- 24440522
TI  - The novel polymeric systems for photodynamic therapy technique.
AB  - Photodynamic therapy (PDT) is a medical treatment in which a combination of a
      photosensitizing drug and visible light causes destruction of selected cells.
      Over the past two decades, photodynamic therapy has enjoyed a period of
      laboratory and in the clinic. Although still widely considered to be an
      experimental technique, its status and value within modern clinical practice
      continues to grow. The PDT field has, to date, been dominated by a small number
      of pharmaceutical companies inhabited almost exclusively by clinicians and those
      involved in fundamental scientific research. True pharmaceutical formulation
      development has been limited, to some extent, by financial constraints. If PDT is
      to realize its undoubted potential in clinical practice it is important that
      awareness of the need for appropriate photosensitizer delivery systems is raised.
      Accordingly, this article deals with the innovations pertaining to drug delivery
      systems for photodynamic therapy as disclosed in recent patent literature. 

PMID- 24440523
TI  - Difficulty in making contact with others and social withdrawal as early signs of
      psychosis in adolescents--the Northern Finland Birth Cohort 1986.
AB  - AIM: Social withdrawal is among the first signs of the prodromal state of
      psychosis seen in clinical samples. The aim of this prospective study was to find
      out whether difficulty in making contact with others and social withdrawal
      precede first episode psychosis in the young general population. METHODS: The
      members of the Northern Finland Birth Cohort 1986 (n=6274) completed the PROD
      screen questionnaire in 2001-2002. The Finnish Hospital Discharge Register was
      used to detect both new psychotic and non-psychotic disorders requiring
      hospitalisation during 2003-2008. RESULTS: Twenty-three subjects developed
      psychosis and 89 developed a non-psychotic mental disorder requiring
      hospitalisation during the follow-up. Of those who developed psychosis, 35% had
      reported difficulty or uncertainty in making contact with others and 30% social
      withdrawal in adolescence. In hospitalised non-psychotic disorder, the
      corresponding precentages were 10 and 13% and in the control group without
      hospital-treated mental disorder 9 and 11%. The differences between psychotic and
      non-psychotic hospitalised subjects (P<0.01) as well as controls (P<0.001) were
      statistically significant regarding difficulty or uncertainty in making contact
      with others. CONCLUSIONS: In this general population-based sample self-reported
      difficulty or uncertainty in making contact with others in adolescence preceded
      psychosis specifically compared to hospitalised non-psychotic mental disorders
      and controls.

PMID- 24440524
TI  - Tau exon 2 responsive elements deregulated in myotonic dystrophy type I are
      proximal to exon 2 and synergistically regulated by MBNL1 and MBNL2.
AB  - The splicing of the microtubule-associated protein Tau is regulated during
      development and is found to be deregulated in a growing number of pathological
      conditions such as myotonic dystrophy type I (DM1), in which a reduced number of
      isoforms is expressed in the adult brain. DM1 is caused by a dynamic and unstable
      CTG repeat expansion in the DMPK gene, resulting in an RNA bearing long CUG
      repeats (n>50) that accumulates in nuclear foci and sequesters CUG-binding
      splicing factors of the muscle blind-like (MBNL) family, involved in the splicing
      of Tau pre-mRNA among others. However, the precise mechanism leading to Tau mis
      splicing and the role of MBNL splicing factors in this process are poorly
      understood. We therefore used new Tau minigenes that we developed for this
      purpose to determine how MBNL1 and MBNL2 interact to regulate Tau exon 2
      splicing. We demonstrate that an intronic region 250 nucleotides downstream of
      Tau exon 2 contains cis-regulatory splicing enhancers that are sensitive to MBNL
      and that bind directly to MBNL1. Both MBNL1 and MBNL2 act as enhancers of Tau
      exon 2 inclusion. Intriguingly, the interaction of MBNL1 and MBNL2 is required to
      fully reverse the mis-splicing of Tau exon 2 induced by the trans-dominant effect
      of long CUG repeats, similar to the DM1 condition. In conclusion, both MBNL1 and
      MBNL2 are involved in the regulation of Tau exon 2 splicing and the mis-splicing
      of Tau in DM1 is due to the combined inactivation of both.

PMID- 24440525
TI  - Exogenous amyloidogenic proteins function as seeds in amyloid beta-protein
      aggregation.
AB  - Amyloid beta-protein (Abeta) aggregation is considered to be a critical step in
      the neurodegeneration of Alzheimer's disease (AD). In addition to Abeta, many
      proteins aggregate into the amyloid state, in which they form elongated fibers
      with spines comprising stranded beta-sheets. However, the cross-seeding effects
      of other protein aggregates on Abeta aggregation pathways are not completely
      clear. To investigate the cross-seeding effects of exogenous and human non-CNS
      amyloidogenic proteins on Abeta aggregation pathways, we examined whether and how
      sonicated fibrils of casein, fibroin, sericin, actin, and islet amyloid
      polypeptide affected Abeta40 and Abeta42 aggregation pathways using the
      thioflavin T assay and electron microscopy. Interestingly, the fibrillar seeds of
      all amyloidogenic proteins functioned as seeds. The cross-seeding effect of actin
      was stronger but that of fibroin was weaker than that of other proteins.
      Furthermore, our nuclear magnetic resonance spectroscopic studies identified the
      binding sites of Abeta with the amyloidogenic proteins. Our results indicate that
      the amyloidogenic proteins, including those contained in foods and cosmetics,
      contribute to Abeta aggregation by binding to Abeta, suggesting their possible
      roles in the propagation of Abeta amyloidosis.

PMID- 24440526
TI  - Morphine modulates cell proliferation through mir133b &mir128 in the
      neuroblastoma SH-SY5Y cell line.
AB  - Neuroblastoma is a childhood cancer with high incidence and high mortality rate.
      Great efforts are made to find new treatments and molecular markers for diagnosis
      and prognosis. miRNAs stand for novel strategies to modulate tumor growth, as
      they can act either as tumor suppressors or as oncogenes. Morphine is an opioid
      agonist widely used to treat severe and chronic pain, as for example cancer pain.
      Previous studies have revealed that morphine is able to modify cancer
      progression, by acting on proliferation or on apoptosis; however, up to date, the
      available results are contradictory, maybe due to the different doses used,
      routes of administration and model systems. While some studies show that morphine
      promotes cell proliferation and metastasis, other authors sustain that morphine
      effect is mainly antiproliferative and pro-apoptotic. In this study we aim to
      establish the effect of chronic opiate administration on cell proliferation in
      the neuroblastoma SH-SY5Y cell line. Low doses of morphine (10nM) promoted cell
      proliferation in undifferentiated cells and reduced the expression levels of
      miR133b, while higher doses (1MUM) inhibited cell proliferation and correlated
      with decreased levels of miR133b and miR128 without triggering apoptosis.
      Naloxone, the classical opioid antagonist, could not fully block the effect of
      morphine on miR128 expression, so that the observed effect may be mediated by non
      opioid mechanisms. Our results represent a further contribution to the hypothesis
      that a joint regulation of miRNA networks and the specific characteristics of the
      target tissue may determine the effect of morphine on tumor cell growth.

PMID- 24440527
TI  - The motor preparation of directionally incompatible movements.
AB  - This work explores, for the first time, the electro-cortical activity related to
      the preparation of bimanual incompatible actions. To accomplish this aim, we
      recorded motor-related cortical potentials (MRCPs) in 16 healthy subjects, who
      were asked to draw lines and/or circles during three experimental conditions:
      Unimanual, Bimanually Compatible (either lines or circles with both hands) and
      Bimanually Incompatible (a line with one hand and a circle with the other hand).
      We show that the electro-cortical activity recorded during the preparation of the
      bimanually incompatible actions included a central positivity (CP) that began
      approximately 2.5s before movement onset and was localized in medial frontal
      areas. We then recorded a later (ca. 700ms before movement onset) negative
      activity in the supplementary motor area (consistent with
      Bereitschaftspotential). Finally, a strong frontal lateral positivity (FLP)
      emerged ca. 1.8s before the initiation of drawing that was localized in the
      dorsolateral prefrontal cortex. All components were bilateral. The CP component
      has not been described before. These data are discussed with regard to the
      "interference network" theory. 

PMID- 24440528
TI  - Development of a high angular resolution diffusion imaging human brain template.
AB  - Brain diffusion templates contain rich information about the microstructure of
      the brain, and are used as references in spatial normalization or in the
      development of brain atlases. The accuracy of diffusion templates constructed
      based on the diffusion tensor (DT) model is limited in regions with complex
      neuronal micro-architecture. High angular resolution diffusion imaging (HARDI)
      overcomes limitations of the DT model and is capable of resolving intravoxel
      heterogeneity. However, when HARDI is combined with multiple-shot sequences to
      minimize image artifacts, the scan time becomes inappropriate for human brain
      imaging. In this work, an artifact-free HARDI template of the human brain was
      developed from low angular resolution multiple-shot diffusion data. The resulting
      HARDI template was produced in ICBM-152 space based on Turboprop diffusion data,
      was shown to resolve complex neuronal micro-architecture in regions with
      intravoxel heterogeneity, and contained fiber orientation information consistent
      with known human brain anatomy. 

PMID- 24440529
TI  - Beta oscillations reflect changes in motor cortex inhibition in healthy ageing.
AB  - Beta oscillations are involved in movement and have previously been linked to
      levels of the inhibitory neurotransmitter GABA. We examined changes in beta
      oscillations during rest and movement in primary motor cortex (M1). Amplitude and
      frequency of beta power at rest and movement-related beta desynchronization
      (MRBD) were measured during a simple unimanual grip task and their relationship
      with age was explored in a group of healthy participants. We were able to show
      that at rest, increasing age was associated with greater baseline beta power in
      M1 contralateral to the active hand, with a similar (non-significant) trend in
      ipsilateral M1. During movement, increasing age was associated with increased
      MRBD amplitude in ipsilateral M1 and reduced frequency (in contralateral and
      ipsilateral M1). These findings would be consistent with greater GABAergic
      inhibitory activity within motor cortices of older subjects. These oscillatory
      parameters have the potential to reveal changes in the excitatory-inhibitory
      balance in M1 which in turn may be a useful marker of plasticity in the brain,
      both in healthy ageing and disease. 

PMID- 24440530
TI  - Re-thinking the role of motor cortex: context-sensitive motor outputs?
AB  - The standard account of motor control considers descending outputs from primary
      motor cortex (M1) as motor commands and efference copy. This account has been
      challenged recently by an alternative formulation in terms of active inference:
      M1 is considered as part of a sensorimotor hierarchy providing top-down
      proprioceptive predictions. The key difference between these accounts is that
      predictions are sensitive to the current proprioceptive context, whereas
      efference copy is not. Using functional electric stimulation to experimentally
      manipulate proprioception during voluntary movement in healthy human subjects, we
      assessed the evidence for context sensitive output from M1. Dynamic causal
      modeling of functional magnetic resonance imaging responses showed that FES
      altered proprioception increased the influence of M1 on primary somatosensory
      cortex (S1). These results disambiguate competing accounts of motor control,
      provide some insight into the synaptic mechanisms of sensory attenuation and may
      speak to potential mechanisms of action of FES in promoting motor learning in
      neurorehabilitation. 

PMID- 24440531
TI  - To cut or not to cut? Assessing the modular structure of brain networks.
AB  - A wealth of methods has been developed to identify natural divisions of brain
      networks into groups or modules, with one of the most prominent being modularity.
      Compared with the popularity of methods to detect community structure, only a few
      methods exist to statistically control for spurious modules, relying almost
      exclusively on resampling techniques. It is well known that even random networks
      can exhibit high modularity because of incidental concentration of edges, even
      though they have no underlying organizational structure. Consequently,
      interpretation of community structure is confounded by the lack of principled and
      computationally tractable approaches to statistically control for spurious
      modules. In this paper we show that the modularity of random networks follows a
      transformed version of the Tracy-Widom distribution, providing for the first time
      a link between module detection and random matrix theory. We compute parametric
      formulas for the distribution of modularity for random networks as a function of
      network size and edge variance, and show that we can efficiently control for
      false positives in brain and other real-world networks. 

PMID- 24440533
TI  - Palmitoylethanolamide inhibits rMCP-5 expression by regulating MITF activation in
      rat chronic granulomatous inflammation.
AB  - Chronic inflammation, a condition frequently associated with several pathologies,
      is characterized by angiogenic and fibrogenic responses that may account for the
      development of granulomatous tissue. We previously demonstrated that the chymase,
      rat mast cell protease-5 (rMCP-5), exhibits pro-inflammatory and pro-angiogenic
      properties in a model of chronic inflammation sustained by mast cells (MCs),
      granuloma induced by the subcutaneous carrageenan-soaked sponge implant in rat.
      In this study, we investigated the effects of palmitoylethanolamide (PEA), an
      anti-inflammatory and analgesic endogenous compound, on rMCP-5 mRNA expression
      and Microphtalmia-associated Transcription Factor (MITF) activation in the same
      model of chronic inflammation. The levels of rMCP-5 mRNA were detected using semi
      quantitative RT-PCR; the protein expression of chymase and extracellular signal
      regulated kinases (ERK) were analyzed by western blot; MITF/DNA binding activity
      and MITF phosphorylation were assessed by electrophoretic mobility shift assay
      (EMSA) and immunoprecipitation, respectively. The administration of PEA (200, 400
      and 800 ug/ml) significantly decreased rMCP-5 mRNA and chymase protein expression
      induced by lambda-carrageenan. These effects were associated with a significant
      decrease of MITF/DNA binding activity and phosphorylated MITF as well as
      phosphorylated ERK levels. In conclusion, our results, showing the ability of PEA
      to inhibit MITF activation and chymase expression in granulomatous tissue, may
      yield new insights into the understanding of the signaling pathways leading to
      MITF activation controlled by PEA.

PMID- 24440532
TI  - Transcriptional co-repressors and memory storage.
AB  - Epigenetic modifications are a central mechanism for regulating chromatin
      structure and gene expression in the brain. A wide array of histone- and DNA
      modifying enzymes have been identified as critical regulators of neuronal
      function, memory formation, and as causative agents in neurodevelopmental and
      neuropsychiatric disorders. Chromatin modifying enzymes are frequently
      incorporated into large multi-protein co-activator and co-repressor complexes,
      where the activity of multiple enzymes is both spatially and temporally
      coordinated. In this review, we discuss negative regulation of gene expression by
      co-repressor complexes, and the role of co-repressors and their binding partners
      in neuronal function, memory, and disease.

PMID- 24440535
TI  - Isolation of Bacillus cytotoxicus from various commercial potato products.
AB  - Bacillus (B.) cytotoxicus is a newly described thermotolerant member of the
      Bacillus cereus group. This potential foodborne pathogen had so far only been
      isolated from vegetable products, including mashed potatoes. Here we report the
      detection of B. cytotoxicus in a variety of potato products taken on retail level
      or from catering establishments (n=151). Identification of isolates as B.
      cytotoxicus was performed after enrichment at 50 degrees C, followed by
      differentiation using Fourier transform-infrared spectroscopy and detection of
      the specific cytK-1 gene by PCR. Thirty-five percent of all samples were positive
      for B. cytotoxicus. Highest prevalence was found in dehydrated potato products
      (44/62=71%) such as powder for mashed potatoes and products made thereof. B.
      cytotoxicus was not detected in products that were evidently made directly from
      potatoes (n=24) but in one sample of raw potatoes (n=10; 10%). The high
      prevalence of this thermotolerant pathogen in potato products could pose a risk
      for consumers, especially if prepared foods are held at improper holding
      temperatures. 

PMID- 24440534
TI  - PTD-mediated intracellular delivery of mutant NFAT minimum DNA binding domain
      inhibited the proliferation of T cells.
AB  - The nuclear factor of activated T cell (NFAT) family of calcium-regulated
      transcription factors plays a key role in the development and function of the
      immune system. Calcineurin, a protein phosphatase, activates NFAT by
      dephosphorylation. The activated NFAT is translocated into the nucleus, where it
      up-regulates the expression of interleukin 2 (IL-2) and other target genes.
      Calcineurin inhibitors such as cyclosporine A (CsA) and FK506 are effective
      immunosuppressant drugs and dramatically increase the success rate of organ
      transplantation procedures. However, since calcineurin is expressed in most
      tissues in the body and calcineurin inhibition alters many cellular processes
      besides immune cell activation, the therapeutic use of calcineurin inhibitors is
      limited by serious side effects. Thus inhibiting NFAT by other mechanisms such as
      blocking its binding to DNA could be a more selective and safer approach to
      target NFAT for therapeutic applications. In peripheral T cells, productive
      immune responses are dependent upon the cooperative binding of the NFAT/AP-1
      transcriptional complex to the promoter regions of genes such as interleukin-2
      (IL-2), while NFAT in the absence of AP-1 leads to T cell anergy. Protein
      transduction domains (PTDs) are able to penetrate cell membranes and can be used
      to transport exogenous proteins across the cell and nuclear membranes. In this
      study, we constructed a fusion protein of PTD and a minimum DNA binding domain of
      human NFAT1 (PTD-DeltaNFATminiDBD), which contains two mutations (R466A and
      T533G) in the AP-1 binding sites. The delivery and functions of this fusion
      protein in T cells were investigated. The results indicated that PTD
      DeltaNFATminiDBD could be effectively delivered into T cells and transported into
      the nucleus. PTD-DeltaNFATminiDBD attenuated IL-2 production in T cells and then
      inhibited T cell proliferation, likely through competing against endogenous NFAT
      for binding to the IL-2 gene promoter. These results demonstrated that PTD
      DeltaNFATminiDBD was an effective NFAT inhibitor with a novel mechanism of action
      and might potentially be used as an immunosuppressant for organ transplantation
      with higher safety and better tolerance than calcineurin inhibitors. 

PMID- 24440536
TI  - Radiation dose around a PET scanner installation: comparison of Monte Carlo
      simulations, analytical calculations and experimental results.
AB  - PURPOSE: Monte Carlo study of radiation transmission around areas surrounding a
      PET room. METHODS: An extended population of patients administered with (18)F-FDG
      for PET-CT investigations was studied, collecting air kerma rate and gamma ray
      spectra measurements at a reference distance. An MC model of the diagnostic room
      was developed, including the scanner and walls with variable material and
      thickness. MC simulations were carried out with the widely used code GEANT4.
      RESULTS: The model was validated by comparing simulated radiation dose values and
      gamma ray spectra produced by a volumetric source with experimental measurements;
      ambient doses in the surrounding areas were assessed for different combinations
      of wall materials and shielding and compared with analytical calculations, based
      on the AAPM Report 108. In the range 1.5-3.0 times of the product between the
      linear attenuation coefficient and thickness of an absorber (MU x), it was
      observed that the effectiveness of different combinations of shielding is roughly
      equivalent. An extensive tabulation of results is given in the text. CONCLUSIONS:
      The validation tests performed showed a satisfactory agreement between the
      simulated and expected results. The simulated dose rates incident on, and
      transmitted by the walls in our model of PET scanner room, are generally in good
      agreement with analytical estimates performed using the AAPM Publication No. 108
      method. This provides an independent confirmation of AAPM's approach. Even in
      this specific field of application, GEANT4 proved to be a relevant and accurate
      tool for dosimetry estimates, shielding evaluation and for general radiation
      protection use.

PMID- 24440537
TI  - Cumulative radiation dose estimates from medical imaging in paediatric patients
      with non-oncologic chronic illnesses. A systematic review.
AB  - Paediatric patients with non-oncologic chronic illnesses often require ongoing
      care that may result in repeated imaging and exposure to ionizing radiation from
      both diagnostic and interventional procedures. In this study the scientific
      literature on cumulative effective dose (CED) of radiation accrued from medical
      imaging among specific cohorts of paediatric, non-oncologic chronic patients
      (inflammatory bowel disease, cystic fibrosis, congenital heart disease, shunt
      treated hydrocephalus, hemophilia, spinal dysraphism) was systematically
      reviewed. We conducted PubMed/Medline, Scopus and EMBASE searches of peer
      reviewed papers on CED from diagnostic and therapeutic radiological examinations.
      No time restriction was introduced in the search. Only studies reporting CEDs
      accrued for a period >1 year were included. We found that the annual CED was
      relatively low (<3 mSv/year) in cystic fibrosis, congenital heart disease,
      patients with cerebrospinal fluid shunts and hemophilia, while being moderate (>3
      20 mSv/year) in Crohn's patients. This extra yearly radiation exposure accrues
      over the lifetime and can reach high values (>100 mSv) in selected cohorts of
      paediatric chronic patients. 

PMID- 24440538
TI  - Optimum design of a moderator system based on dose calculation for an accelerator
      driven Boron Neutron Capture Therapy.
AB  - An accelerator based BNCT has been desired because of its therapeutic
      convenience. However, optimal design of a neutron moderator system is still one
      of the issues. Therefore, detailed studies on materials consisting of the
      moderator system are necessary to obtain the optimal condition. In this study,
      the epithermal neutron flux and the RBE dose have been calculated as the
      indicators to look for optimal materials for the filter and the moderator. As a
      result, it was found that a combination of MgF2 moderator with Fe filter gave
      best performance, and the moderator system gave a dose ratio greater than 3 and
      an epithermal neutron flux over 1.0*10(9)cm(-2)s(-1). 

PMID- 24440539
TI  - Standardization and determination of the total internal conversion coefficient of
      In-111.
AB  - The standardization of (111)In by means of a 4pibeta-gamma coincidence system,
      composed of a proportional counter in 4pi geometry, coupled to a 20% relative
      efficiency HPGe crystal, for measuring gamma-rays is presented. The data
      acquisition was performed by means of the software coincidence system (SCS) and
      the activity was determined by the extrapolation technique. Two gamma-ray windows
      were selected: at 171 keV and 245 keV total absorption peaks, allowing the
      determination of the total internal conversion coefficient for these two gamma
      transitions. The results were compared with those available in the literature.

PMID- 24440540
TI  - Nine-year interval recurrence after treatment of boron neutron capture therapy in
      a patient with glioblastoma: a case report.
AB  - Boron neutron capture therapy (BNCT) has been reported to be effective in the
      patients with glioblastoma multiforme (GBM). Median survival time (MST) of GBM
      patients treated with BNCT is approximately two years. GBM patients surviving 2
      or 3 years are considered long-term survivors. In general, most recurrences are
      local and dissemination is rare. We report an unusual patient with three
      recurrences; the first and the second recurrences were local, and the third
      recurrence was dissemination nine years after BNCT. 

PMID- 24440541
TI  - Alcohol quantity and type on risk of recurrent gout attacks: an internet-based
      case-crossover study.
AB  - OBJECTIVES: Although beer and liquor have been associated with risk of incident
      gout, wine has not. Yet anecdotally, wine is thought to trigger gout attacks.
      Further, how much alcohol intake is needed to increase the risk of gout attack is
      not known. We examined the quantity and type of alcohol consumed on risk of
      recurrent gout attacks. METHODS: We conducted a prospective Internet-based case
      crossover study in the US among participants with gout and who had at least one
      attack during the 1 year of follow-up. We evaluated the association of alcohol
      intake over the prior 24 hours as well as the type of alcoholic beverage with
      risk of recurrent gout attack, adjusting for potential time-varying confounders.
      RESULTS: This study included 724 participants with gout (78% men, mean age 54
      years). There was a significant dose-response relationship between amount of
      alcohol consumption and risk of recurrent gout attacks (P <.001 for trend). The
      risk of recurrent gout attack was 1.36 (95% confidence interval [CI], 1.00-1.88)
      and 1.51 (95% CI, 1.09-2.09) times higher for >1-2 and >2-4 alcoholic beverages,
      respectively, compared with no alcohol consumption in the prior 24 hours.
      Consuming wine, beer, or liquor was each associated with an increased risk of
      gout attack. CONCLUSIONS: Episodic alcohol consumption, regardless of type of
      alcoholic beverage, was associated with an increased risk of recurrent gout
      attacks, including potentially with moderate amounts. Individuals with gout
      should limit alcohol intake of all types to reduce the risk of recurrent gout
      attacks.

PMID- 24440542
TI  - PICC-associated bloodstream infections: prevalence, patterns, and predictors.
AB  - BACKGROUND: Growing use of peripherally inserted central catheters (PICCs) has
      led to recognition of the risk of PICC-associated bloodstream infection. We
      sought to identify rates, patterns, and patient, provider, and device
      characteristics associated with this adverse outcome. METHODS: A retrospective
      cohort of consecutive adults who underwent PICC placement from June 2009 to July
      2012 was assembled. Using multivariable logistic and Cox-proportional hazards
      regression models, covariates specified a priori were analyzed for their
      association with PICC-associated bloodstream infection. Odds ratios (OR) and
      hazard ratios (HR) with corresponding 95% confidence intervals (CI) were used to
      express the association between each predictor and the outcome of interest.
      RESULTS: During the study period, 966 PICCs were inserted in 747 unique patients
      for a total of 26,887 catheter days. Indications for PICC insertion included:
      long-term antibiotic administration (52%, n = 503), venous access (21%, n = 201),
      total parenteral nutrition (16%, n = 155), and chemotherapy (11%, n = 107). On
      bivariate analysis, intensive care unit (ICU) status (OR 3.23; 95% CI, 1.84
      5.65), mechanical ventilation (OR 4.39; 95% CI, 2.46-7.82), length of stay
      (hospital, OR 1.04; 95% CI, 1.02-1.06 and ICU, OR 1.03; 95% CI, 1.02-1.04),
      PowerPICCs (C. R. Bard, Inc., Murray Hill, NJ; OR 2.58; 95% CI, 1.41-4.73), and
      devices placed by interventional radiology (OR 2.57; 95% CI, 1.41-4.68) were
      associated with PICC-bloodstream infection. Catheter lumens were strongly
      associated with this event (double lumen, OR 5.21; 95% CI, 2.46-11.04, and triple
      lumen, OR 10.84; 95% CI, 4.38-26.82). On multivariable analysis, only hospital
      length of stay, ICU status, and number of PICC lumens remained significantly
      associated with PICC bloodstream infection. Notably, the HR for PICC lumens
      increased substantially, suggesting earlier time to infection among patients with
      multi-lumen PICCs (HR 4.08; 95% CI, 1.51-11.02 and HR 8.52; 95% CI, 2.55-28.49
      for double- and triple-lumen devices, respectively). CONCLUSIONS: PICC-associated
      bloodstream infection is most associated with hospital length of stay, ICU
      status, and number of device lumens. Policy and procedural oversights targeting
      these factors may be necessary to reduce the risk of this adverse outcome.

PMID- 24440543
TI  - Treat or eat: food insecurity, cost-related medication underuse, and unmet needs.
AB  - BACKGROUND: Adults with chronic disease are often unable to meet medication and
      food needs, but no study has examined the relationship between cost-related
      medication underuse and food insecurity in a nationally representative sample. We
      examined which groups most commonly face unmet food and medication needs.
      METHODS: Cross-sectional analysis of data from chronically ill participants (self
      report of arthritis, diabetes mellitus, cancer, asthma, chronic obstructive
      pulmonary disease, stroke, hypertension, coronary heart disease, or presence of a
      "psychiatric problem") aged >=20 years, in the 2011 National Health Interview
      Survey. We fit logistic regression models to identify factors associated with
      food insecurity, cost-related medication underuse, or both. RESULTS: There were
      9696 adult National Health Interview Survey (NHIS) participants who reported
      chronic illness; 23.4% reported cost-related medication underuse; 18.8% reported
      food insecurity; and 11% reported both. Adults who reported food insecurity were
      significantly more likely to report cost-related medication underuse (adjusted
      odds ratio [aOR] 4.03). Participants with both cost-related medication underuse
      and food insecurity were more likely to be Hispanic (aOR 1.58), non-Hispanic
      black (aOR 1.58), and have more chronic conditions (aOR per additional chronic
      condition 1.56) than patients reporting neither. They also were less likely to
      have public, non-Medicare insurance (aOR 0.70) and report participation in the
      Special Supplemental Nutrition Assistance Program for Woman, Infants, and
      Children (aOR 0.39). CONCLUSIONS: Approximately 1 in 3 chronically ill NHIS
      participants are unable to afford food, medications, or both. WIC and public
      health insurance participation are associated with less food insecurity and cost
      related medication underuse.

PMID- 24440544
TI  - Are there circumstances where I would refuse to participate in caring for a
      patient?

PMID- 24440545
TI  - Acrylic prostheses in surgery of the hip (1st) report by R. Judet).

PMID- 24440546
TI  - Sacro-iliac joint arthroscopy for arthrodesis after traumatic dislocation.
      Cadaver and clinical feasibility study.
AB  - BACKGROUND: Sacro-iliac arthrodesis usually requires an extended posterior
      approach, which is associated with a number of dreaded complications. Here, we
      assessed the feasibility of arthroscopic exploration of the dislocated sacro
      iliac joint. MATERIALS AND METHODS: In the first step of our study, we used
      ligament section to induce loss of sacro-iliac joint coaptation in a cadaver. We
      then studied 5 patients with Tile C pelvic ring injuries. Arthroscopy was used to
      clear the joint of fibrous tissue and to roughen the bone to subchondral level in
      order to induce sacro-iliac arthrodesis. In addition, posterior fixation was
      performed using a hinge system or an ilio-sacral screw. RESULTS: The cadaver
      study confirmed the feasibility of sacro-iliac arthroscopy after disruption of
      the strong posterior inter-osseous ligament. In the clinical part of the study in
      5 patients with Tile C pelvic ring injuries, arthroscopy allowed direct
      visualisation extending to the anterior part of the joint space. A power burr and
      synovial knife were introduced to remove the interposed fibrous tissue and to
      roughen the bone to subchondral level in order to induce joint fusion. In
      addition, percutaneous or open posterior fixation was performed in all 5
      patients. No infectious complications were recorded. DISCUSSION: An arthroscope
      cannot be introduced into the normal sacro-iliac joint. In contrast, after
      traumatic sacro-iliac dislocation, arthroscopy can be used to evaluate the intra
      articular injuries and to roughen the bone to subchondral level.

PMID- 24440547
TI  - Reconstruction of the iliac bone using the homolateral femur after resection for
      pelvic tumor.
AB  - The authors have treated three patients with extensive involvement of the
      acetabular and peri-acetabular bone by a malignant tumour. One had a metastasis
      from a carcinoma of the thyroid, one from a carcinoma of the breast and one a
      plasmacytoma. In all three cases, the upper part of the femur was unaffected. It
      was used to replace the resected pelvic bone and fixed to the remaining bone by
      screws and plates. An acetabular cup was cemented into the transplanted bone,
      which itself was replaced by a massive femoral prosthesis. This technique allowed
      the patients to resume weight bearing rapidly. Two patients were alive and walked
      satisfactorily after two and four years respectively. The third died five months
      after the surgical procedure. 

PMID- 24440548
TI  - Bayesian models for screening and TB Mobile for target inference with
      Mycobacterium tuberculosis.
AB  - The search for compounds active against Mycobacterium tuberculosis is reliant
      upon high-throughput screening (HTS) in whole cells. We have used Bayesian
      machine learning models which can predict anti-tubercular activity to filter an
      internal library of over 150,000 compounds prior to in vitro testing. We used
      this to select and test 48 compounds in vitro; 11 were active with MIC values
      ranging from 0.4 MUM to 10.2 MUM, giving a high hit rate of 22.9%. Among the
      hits, we identified several compounds belonging to the same series including five
      quinolones (including ciprofloxacin), three molecules with long aliphatic linkers
      and three singletons. This approach represents a rapid method to prioritize
      compounds for testing that can be used alongside medicinal chemistry insight and
      other filters to identify active molecules. Such models can significantly
      increase the hit rate of HTS, above the usual 1% or lower rates seen. In
      addition, the potential targets for the 11 molecules were predicted using TB
      Mobile and clustering alongside a set of over 740 molecules with known M.
      tuberculosis target annotations. These predictions may serve as a mechanism for
      prioritizing compounds for further optimization. 

PMID- 24440550
TI  - [Care as a cross-cutting element in the health care of complex chronic patients].
AB  - The care of people who live with chronic diseases is currently a priority on the
      roadmaps of all health care services. Within these strategies, there needs to be
      a specific approach required for a population group that is defined by having
      multiple diseases and the associated comorbidity. This group is especially
      vulnerable, fragile, and require very complex care, which uses up a high quantity
      of social health resources. The estimated prevalence in Spain is 1.4% in the
      general population, and approximately 5% in people over 64 years. The social and
      healthcare of this population requires a person-centered approach, as a paradigm
      of caring for the patients and not of the diseases. The models must leap from the
      segmented approach to diseases to a holistic and integrated vision, taking into
      account the social and psycho-affective situation, the experience of the patient,
      the family context, and the approach of human experience/response that these
      processes produce. The health professionals need support tools that can guide
      them and help in making clinical decisions in this population group. The clinical
      practice guidelines for the approach of patients with co-morbidity and multiple
      diseases have numerous limitations. Expert recommendations in this sense, lead us
      to a multidisciplinary approach, with self-care and self-health management as a
      cross-cutting element of healthcare. 

PMID- 24440549
TI  - Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium
      tuberculosis.
AB  - Tuberculosis is one of the leading causes of mortality throughout the world.
      Mycobacterium tuberculosis, the causative agent of human tuberculosis, has
      developed several strategies involving proteins and other compounds known
      collectively as virulence factors to subvert human host defences and invade the
      human host. The Mce proteins are among these virulence-related proteins and are
      encoded by the mce1, mce2, mce3 and mce4 operons in the genome of M.
      tuberculosis. It has been proposed that these operons encode ABC-like lipid
      transporters; however, the nature of their substrates has only been revealed in
      the case of the Mce4 proteins. Here we found that the knockout of the mce1 operon
      alters the lipid profile of M. tuberculosis H37Rv and the uptake of palmitic
      acid. Thin layer chromatography and liquid chromatography-mass spectrometry
      analysis showed that the mce1 mutant accumulates more mycolic acids than the wild
      type and complemented strains. Interestingly, this accumulation of mycolic acid
      is exacerbated when bacteria are cultured in the presence of palmitic acid or
      arachidonic acid. These results suggest that the mce1 operon may serve as a
      mycolic acid re-importer. 

PMID- 24440551
TI  - [Telematic consultations by nursing staff for patients with inflammatory bowel
      disease: evaluation of its capacity for resolving problems and its costs].
AB  - INTRODUCTION: The management of patients with inflammatory bowel disease (IBD) is
      associated with a significant use of healthcare resources. In 2009, a digestive
      diseases nursing consultation, with availability of health telematic media was
      created in our hospital (CHUVI). The important activity performed in this area
      encouraged us to quantify the cost savings for the care health system. AIMS: 1)
      To evaluate the results of the implementation of a telematic IBD consultation. 2)
      To assess the capacity for resolving problems by nurses. 3) To estimate the
      potential cost savings of telematic nursing consultation in IBD. MATERIAL AND
      METHOD: We collected data on telematic activity from 2009 to 2011. The estimated
      cost saving was calculated by applying the fees for health services published by
      our National Health Service (SERGAS) for care in new outbreaks of IBD activity.
      Data were analyzed with SPSS 15.0 RESULTS: There was a significant linear
      increase on the resolution of telephone demands by nurses (P=.03) and an
      important decrease of demands needing medical advice (P<.0001). Focusing on IBD
      outbreak claims (n=452), only 65 patients (14.38%) required medical attention in
      emergency services, and 33 (7.3%) were hospitalized. Altogether we calculated an
      average cost saving since 2009 to 2011 of 73,603?. CONCLUSIONS: We found a
      gradual increase in resolving telematic care demands by nurses. Telematic
      consultation can lead to significant cost savings, which justify the
      implementation of a digestive diseases nurse consultation.

PMID- 24440552
TI  - Delayed BDNF alterations in the prefrontal cortex of rats exposed to prenatal
      stress: preventive effect of lurasidone treatment during adolescence.
AB  - Psychiatric diseases may often represent the consequence of exposure to adverse
      events early in life. Accordingly, exposure to stress during gestation in rats
      has a strong impact on development and can cause long-term abnormalities in adult
      behavior. Considering that neuronal plasticity has emerged as a major
      vulnerability element in psychiatric disorders, we investigated the postnatal
      developmental profile of Brain-Derived Neurotrophic Factor expression (BDNF), an
      important mediator for long-term functional deterioration associated to mental
      illness, in male and female rats following exposure to prenatal stress (PNS).
      Since we found that the majority of alterations became fully manifest at early
      adulthood, we tried to prevent these abnormalities with an early pharmacological
      intervention. To address this point, we treated rats during adolescence with the
      multi-receptor antipsychotic lurasidone, which was proven to be effective in
      animal models of schizophrenia. Interestingly, we show that lurasidone treatment
      was able to prevent the reduction of BDNF expression in adult rats that were
      exposed to PNS. Collectively, our results provide further support to the notion
      that exposure to early life stress has a negative impact on neuronal plasticity
      and that pharmacological intervention during critical time windows may prove
      effective in preventing neuroplastic dysfunction, leading to long-term beneficial
      effects on brain function. 

PMID- 24440553
TI  - Transferring inpatient rehabilitation facility cancer patients back to acute care
      (TRIPBAC).
AB  - OBJECTIVE: To determine predictive factors for TRansferring Inpatient
      rehabilitation facility (IRF) cancer Patients Back to Acute Care (TRIPBAC).
      DESIGN: A retrospective chart review of patients with cancer admitted to an IRF
      from 2009 to 2010 because of a functional impairment that developed as a direct
      consequence of their cancer or its treatment. SETTING: IRF of a community-based,
      academic, tertiary care facility. METHODS: The characterization of patients with
      cancer in the IRF was primarily based on analysis of the IRF Patient Assessment
      Instrument and other internal IRF data logs. MAIN OUTCOME MEASUREMENT: Frequency
      and reasons for TRIPBAC. RESULTS: The TRIPBAC rate in our IRF was 17.4%. The most
      common reasons for TRIPBAC were postneurosurgical complications (31%). Factors
      associated with TRIPBAC were a motor Functional Independence Measure score of 35
      points or lower on admission (odds ratio 4.01, 95% confidence interval 1.79-8.98;
      P = .001) and the presence of a feeding tube or a modified diet (odds ratio 3.18,
      95% confidence interval 1.44-7.04; P = .004). CONCLUSIONS: Motor Functional
      Independence Measure score on admission is the best predictor for TRIPBAC in
      patients with cancer admitted to our IRF, followed by the presence of a feeding
      tube or a modified diet.

PMID- 24440554
TI  - Bilayer surface association of the pHLIP peptide promotes extensive backbone
      desolvation and helically-constrained structures.
AB  - Despite their presence in many aspects of biology, the study of membrane proteins
      lags behind that of their soluble counterparts. Improving structural analysis of
      membrane proteins is essential. Deep-UV resonance Raman (DUVRR) spectroscopy is
      an emerging technique in this area and has demonstrated sensitivity to subtle
      structural transitions and changes in protein environment. The pH low insertion
      peptide (pHLIP) has three distinct structural states: disordered in an aqueous
      environment, partially folded and associated with a lipid membrane, and inserted
      into a lipid bilayer as a transmembrane helix. While the soluble and membrane
      inserted forms are well characterized, the partially folded membrane-associated
      state has not yet been clearly described. The amide I mode, known to be sensitive
      to protein environment, is the same in spectra of membrane-associated and
      membrane-inserted pHLIP, indicating comparable levels of backbone dehydration.
      The amide S mode, sensitive to helical structure, indicates less helical
      character in the membrane-associated form compared to the membrane-inserted
      state, consistent with previous findings. However, the structurally sensitive
      amide III region is very similar in both membrane-associated and membrane
      inserted pHLIP, suggesting that the membrane-associated form has a large amount
      of ordered structure. Where before the membrane-associated state was thought to
      contain mostly unordered structure and reside in a predominantly aqueous
      environment, we have shown that it contains a significant amount of ordered
      structure and rests deeper within the lipid membrane. 

PMID- 24440555
TI  - Melia azedarach plants show tolerance properties to water shortage treatment: an
      ecophysiological study.
AB  - Candidate species for reforestation of areas prone to drought must combine water
      stress (WS) tolerance and economic or medicinal interest. Melia azedarach
      produces high quality timber and has insecticidal and medicinal properties.
      However, the impact of WS on M. azedarach has not yet been studied. Two-month old
      M. azedarach plants were exposed to WS during 20 days. After this period, plant's
      growth, water potential, photosynthetic performance and antioxidant capacity were
      evaluated. WS did not affect plants' growth, but induced stomatal closure,
      reduced net CO2 assimilation rate (A) and the intercellular CO2 availability in
      mesophyll (C(i)). WS also reduced the photosynthetic efficiency of PSII but not
      the pigment levels. WS up-regulated the antioxidant enzymes and stimulated the
      production of antioxidant metabolites, preventing lipid peroxidation. Therefore,
      despite some repression of photosynthetic parameters by WS, they did not
      compromise plant growth, and plants increased their antioxidant capacity. Our
      data demonstrate that M. azedarach juvenile plants have the potential to
      acclimate to water shortage conditions, opening new perspectives to the use of
      this species in reforestation/afforestation programs of drought prone areas.

PMID- 24440556
TI  - PPARgamma1 phosphorylation enhances proliferation and drug resistance in human
      fibrosarcoma cells.
AB  - Post-translational regulation plays a critical role in the control of cell growth
      and proliferation. The phosphorylation of peroxisome proliferator-activated
      receptor gamma (PPARgamma) is the most important post-translational modification.
      The function of PPARgamma phosphorylation has been studied extensively in the
      past. However, the relationship between phosphorylated PPARgamma1 and tumors
      remains unclear. Here we investigated the role of PPARgamma1 phosphorylation in
      human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to
      alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of
      PPARgamma1, the results suggested that phosphorylation attenuated PPARgamma1
      transcriptional activity. Meanwhile, we demonstrated that phosphorylated
      PPARgamma1 promoted HT1080 cell proliferation and this effect was dependent on
      the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase
      inhibitor (CKI) p21(Waf1/Cip1) and p27(Kip1) descended in PPARgamma1(S84D) stable
      HT1080 cell, whereas the expression of p18(INK4C) was not changed. Moreover,
      compared to the PPARgamma1(S84A), PPARgamma1(S84D) up-regulated the expression
      levels of cyclin D1 and cyclin A. Finally, PPARgamma1 phosphorylation reduced
      sensitivity to agonist rosiglitazone and increased resistance to anticancer drug
      5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARgamma1
      phosphorylation as a critical event in human fibrosarcoma growth. These findings
      raise the possibility that chemical compounds that prevent the phosphorylation of
      PPARgamma1 could act as anticancer drugs. 

PMID- 24440557
TI  - Library preparation methods for next-generation sequencing: tone down the bias.
AB  - Next-generation sequencing (NGS) has caused a revolution in biology. NGS requires
      the preparation of libraries in which (fragments of) DNA or RNA molecules are
      fused with adapters followed by PCR amplification and sequencing. It is evident
      that robust library preparation methods that produce a representative, non-biased
      source of nucleic acid material from the genome under investigation are of
      crucial importance. Nevertheless, it has become clear that NGS libraries for all
      types of applications contain biases that compromise the quality of NGS datasets
      and can lead to their erroneous interpretation. A detailed knowledge of the
      nature of these biases will be essential for a careful interpretation of NGS data
      on the one hand and will help to find ways to improve library quality or to
      develop bioinformatics tools to compensate for the bias on the other hand. In
      this review we discuss the literature on bias in the most common NGS library
      preparation protocols, both for DNA sequencing (DNA-seq) as well as for RNA
      sequencing (RNA-seq). Strikingly, almost all steps of the various protocols have
      been reported to introduce bias, especially in the case of RNA-seq, which is
      technically more challenging than DNA-seq. For each type of bias we discuss
      methods for improvement with a view to providing some useful advice to the
      researcher who wishes to convert any kind of raw nucleic acid into an NGS
      library. 

PMID- 24440558
TI  - Structural and functional characterization of the Geobacillus copper nitrite
      reductase: involvement of the unique N-terminal region in the interprotein
      electron transfer with its redox partner.
AB  - The crystal structures of copper-containing nitrite reductase (CuNiR) from the
      thermophilic Gram-positive bacterium Geobacillus kaustophilus HTA426 and the
      amino (N)-terminal 68 residue-deleted mutant were determined at resolutions of
      1.3A and 1.8A, respectively. Both structures show a striking resemblance with the
      overall structure of the well-known CuNiRs composed of two Greek key beta-barrel
      domains; however, a remarkable structural difference was found in the N-terminal
      region. The unique region has one beta-strand and one alpha-helix extended to the
      northern surface of the type-1 copper site. The superposition of the Geobacillus
      CuNiR model on the electron-transfer complex structure of CuNiR with the redox
      partner cytochrome c551 in other denitrifier system led us to infer that this
      region contributes to the transient binding with the partner protein during the
      interprotein electron transfer reaction in the Geobacillus system. Furthermore,
      electron-transfer kinetics experiments using N-terminal residue-deleted mutant
      and the redox partner, Geobacillus cytochrome c551, were carried out. These
      structural and kinetics studies demonstrate that the region is directly involved
      in the specific partner recognition. 

PMID- 24440559
TI  - Effect of TMAO and betaine on the energy landscape of photosystem I.
AB  - The accumulation of organic co-solvents in cells is a basic strategy for
      organisms from various species to increase stress tolerance in extreme
      environments. Widespread representatives of this class of co-solvents are
      trimethylamine-N-oxide (TMAO) and betaine; these small molecules are able to
      stabilize the native conformation of proteins and prevent their aggregation.
      Despite their importance, detailed experimental studies on the impact of these co
      solvents on the energy landscape of proteins have not yet been carried out. We
      use single-molecule spectroscopy at cryogenic temperatures to examine the
      influence of these physiological relevant co-solvents on photosystem I (PSI) from
      Thermosynechococcus elongatus. In contrast to PSI ensemble spectra, which are
      almost unaffected by the addition of TMAO and betaine, statistical analysis of
      the fluorescence emission from individual PSI trimers yields insight into the
      interaction of the co-solvents with PSI. The results show an increased
      homogeneity upon addition of TMAO or betaine. The number of detectable zero
      phonon lines (ZPLs) is reduced, indicating spectral diffusion processes with
      faster rates. In the framework of energy landscape model these findings indicate
      that co-solvents lead to reduced barrier heights between energy valleys, and thus
      efficient screening of protein conformations can take place. 

PMID- 24440560
TI  - Intestinal barrier dysfunction triggered by invasive bacteria.
AB  - The ability to control uptake across the mucosa and to protect the gut from
      harmful substances present in the lumen is defined as intestinal barrier
      function. Two routes are usually distinguished for transepithelial transport. The
      paracellular route allows the passage of ions and small molecules and is mainly
      regulated by tight junctions (TJ). The transcellular route concerns large
      molecules or small particles (including bacteria) and is mediated by cell
      endocytosis and intracellular vesicular traffic. Enteropathogenic bacteria
      increase the transcellular permeability, especially in the follicle-associated
      epithelium. They also modulate TJ opening via the redistribution of TJ proteins
      and the activation of the myosin light chain kinase (MLCK). This review focuses
      on the molecular mechanisms involved in the bacteria-induced barrier defect and
      briefly discusses their consequences in human diseases. 

PMID- 24440561
TI  - Dermal exposure to methamphetamine hydrochloride contaminated residential
      surfaces II. Skin surface contact and dermal transfer relationship.
AB  - This in vitro investigation evaluated [(14)C] - d-methamphetamine hydrochloride
      ([(14)C]-meth HCl) transfer from contaminated vinyl tile (non-porous and smooth)
      and upholstery fabric (rough and loose) to human skin. (14)C-Meth HCl transfer
      rate from vinyl to skin was rapid; a contact duration as brief as 15s resulted in
      measurable radioactivity in the skin and receptor fluid samples. In contrast, the
      transfer from fabric occurred more slowly: the amount of [(14)C]-meth HCl that
      was transferred from dry fabric after 2-h skin contact was one-fifth the amount
      transferred from vinyl after 5-min contact time. With moistened fabric, the
      transfer efficiency to skin after 2-h contact was seven times greater than that
      of dry fabric. While the duration of surface-skin contact appeared to affect the
      total dermal absorption of [(14)C]-meth HCl, it had little effect on the time
      point of maximum transdermal absorption. [(14)C]-meth HCl retained in skin
      continued to be absorbed after the contaminated material was removed. Mass
      balance in these studies was approximately 96%. In conclusion, [(14)C]-meth HCl
      penetrates into/through human skin quickly following skin contact with
      contaminated materials. The porosity of the contact surface and the moisture
      content appears to alter the degree of transfer and dermal penetration. 

PMID- 24440562
TI  - Reply: To PMID 23938610.

PMID- 24440563
TI  - Measurement of hs-CRP is irrelevant to diagnose and stage endometriosis:
      prospective study of 834 patients.
AB  - OBJECTIVE: The pathogenesis of endometriosis is associated with an inflammatory
      process. Here, we assessed if the levels of high-sensitivity C-reactive protein
      (hs-CRP) in serum could constitute an effective method for detecting systemic
      inflammation during endometriosis. STUDY DESIGN: This was a prospective,
      laboratory-based study, which was carried out in a tertiary care university
      hospital. Patients with histologically proven endometriosis (n = 370) and
      unaffected women (n = 464) were enrolled from January 2005 through December 2009.
      We performed complete surgical excision of endometriotic lesions with
      pathological analysis. In addition, hs-CRP levels were determined through a
      particle-enhanced immunoturbidimetric method. The hs-CRP levels were measured in
      both controls and women with endometriosis according to the established surgical
      classifications of endometriosis: superficial peritoneal endometriosis,
      endometrioma, and deep infiltration endometriosis. Also, hs-CRP levels were
      evaluated according to hormonal treatment and menstrual cycle. RESULTS: The hs
      CRP serum levels did not statistically differ between women with endometriosis
      and controls (median in ng/mL [range]: 0.82 [0.04-42.89] vs 0.9 [0.03-43.73],
      respectively; P = .599). Moreover, subgroup analysis revealed no difference among
      superficial peritoneal endometriosis, endometrioma, deep infiltration
      endometriosis, and controls: 0.8 (0.15-13.35), 0.81 (0.04-38.82), 0.83 (0.09
      42.89), and 0.9 (0.03-43.73), respectively; P = .872. Furthermore, no effect was
      observed regarding hormonal treatment or menstrual cycle. CONCLUSION: Although
      endometriosis is an inflammatory disease, we failed to identify any systemic
      changes in hs-CRP serum levels. Therefore, hs-CRP analysis appears to be
      irrelevant to the diagnosis and staging of endometriosis.

PMID- 24440564
TI  - Autism and induced labor: is calcium a potential mechanistic link?

PMID- 24440565
TI  - Cardiac dysfunction is associated with altered sarcomere ultrastructure in
      intrauterine growth restriction.
AB  - OBJECTIVE: The purpose of this study was to assess whether abnormal cardiac
      function in human fetuses with intrauterine growth restriction (IUGR) is
      associated with ultrastructural differences in the cardiomyocyte sarcomere. STUDY
      DESIGN: Nine severe early-onset IUGR fetuses and 9 normally grown fetuses
      (appropriate growth for gestational age) who died in the perinatal period were
      included prospectively. Cardiac function was assessed by echocardiography and
      levels of B-type natriuretic peptide and troponin-I. Heart sections were imaged
      by second harmonic generation microscopy, which allowed unstained visualization
      of cardiomyocyte's sarcomere length. RESULTS: Echocardiographic and biochemical
      markers showed signs of severe cardiac dysfunction in IUGR fetuses. Second
      harmonic generation microscopy demonstrated a significantly shorter sarcomere
      length in IUGR as compared with appropriate growth for gestational age fetuses.
      CONCLUSION: IUGR is associated with changes in the cardiomyocyte contractile
      machinery in the form of shorter sarcomere length, which could help to explain
      the cardiac dysfunction previously documented in IUGR.

PMID- 24440566
TI  - Synthesis of sFlt-1 by platelet-monocyte aggregates contributes to the
      pathogenesis of preeclampsia.
AB  - OBJECTIVE: Soluble fms-like tyrosine kinase (sFlt-1) is an important mediator in
      the pathogenesis of preeclampsia. We sought to determine whether platelet
      monocyte aggregates (PMAs) produced sFlt-1 and whether PMAs contributed to sFlt-1
      production in preeclampsia. STUDY DESIGN: This was a case-control study of sFlt-1
      release from PMAs using blood samples from women with preeclampsia matched by
      gestational age to pregnant controls. A third group of nonpregnant, reproductive
      age women comprised an additional control group. Experiments were also performed
      using blood from nonpregnant women to elucidate whether inducing PMAs could
      stimulate sFlt-1 production and, if so, to determine the necessary receptors and
      pathways. RESULTS: Women with preeclampsia had increased total Flt-1
      concentrations in platelets and monocytes at baseline compared with pregnant
      controls (25 vs 10 pg/mL, P = .0003). sFlt-1 production was elicited from
      monocytes incubated with thrombin-activated platelets from nonpregnant women.
      sFlt-1 production was regulated at the transcriptional level by p38 and nuclear
      factor-kappaB-dependent pathways. CONCLUSION: Activated platelets in preeclampsia
      bind monocytes to generate sFlt-1. PMAs are a previously unrecognized source of
      sFlt-1 that may contribute to endothelial dysfunction and systemic inflammation
      commonly observed in preeclampsia.

PMID- 24440567
TI  - Molecular mechanism for the effects of E. coli heat-labile enterotoxin on mouse
      embryo survival.
AB  - Heat-labile enterotoxin (LT) can cause animal enteritis and diarrhea. However,
      the possible association of LT with embryo survival in pregnant animals and the
      mechanisms involved remain unknown. To investigate the effects of LT on embryo
      survival, we treated mouse early embryos in vitro and pregnant mice in vivo with
      recombinant LT. LT significantly decreased mouse embryo survival, and induced IFN
      gamma, IL-2 and IL-1beta production in the serum and placental tissue. LT also
      triggered IL-1beta release from LPS-primed microphages, suggesting LT can
      activate inflammasomes. To determine the pathway involved in LT-induced
      inflammasome activation, small interfering RNAs were used to knockdown NLRP3 and
      ASC, the key components of NLRP3 inflammasome pathway. Ablation of NLRP3 and ASC
      abolished LT-induced IL-1beta release, confirming the involvement of NLRP3
      inflammasome. By comparing two subunits of LT, only LTA but not LTB subunit was
      identified to activate the NLRP3 inflammasome. 

PMID- 24440568
TI  - Significant association between IL23R and IL17F polymorphisms and clinical
      features of colorectal cancer.
AB  - Th17cells are involved in inflammatory and autoimmune diseases. These cells may
      be involved in pathological processes mainly producing pro-inflammatory
      cytokines. Recently, it was shown that the IL23/IL17 pathway plays an important
      role in the development of inflammatory bowel disease. In general, genes encoding
      cytokines are genetically polymorphic and polymorphisms in genes IL23R el IL17F
      were shown associated with susceptibility to Crohn's disease and ulcerative
      colitis which in their turn are considered as risk factors for developing
      colorectal cancer (CRC). Our approach is to study IL17F and IL23R polymorphisms
      as risk factor associated with CRC in the Tunisian population in patients and
      healthy controls. Interesting, we noted a significant association between IL17F
      and IL23R polymorphisms and tumor location (p=0.0001 and p=0.049, respectively),
      tumor histology (p=0.007 and p=0.049, respectively) and tumor architecture
      (p=0.0000000001 and p=0.07, respectively) in CRC patients. We also showed a
      significant association of IL17F variant with an increased risk of TNM stage
      III/IV (p=0.007), showing an increased risk of advanced stage. Finally, we
      observed a positive link between IL17F polymorphism and CRC patients with lymph
      nodes (p=0.0000000001) and metastasis (p=0.00000009). However, we found no
      evidence to support a significant association between IL17F and IL23R
      polymorphisms and colorectal cancer susceptibility. Our findings suggest that
      IL17F and IL23R polymorphisms were significantly associated with clinical
      features variables. The IL17F cytokine appear to be involved in the control of
      tumor growth and invasion of gastrointestinal tumors. IL17 and IL23 polymorphisms
      or those of their receptors as important determinants of susceptibility to
      colorectal cancer are still subject to questioning. 

PMID- 24440569
TI  - Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel
      adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen
      receptor (GPR30)-to-calpain signaling axis.
AB  - Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone
      sensitive breast cancer, yet initial or acquired resistance to endocrine
      therapies frequently arises and, in particular, cancer recurs as metastasis. We
      demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion
      to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1
      (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating
      calpain activation. Additionally, either E2 or ICI induced down-regulation of
      estrogen receptor alpha without affecting G protein coupled estrogen receptor 30
      (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis
      but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent
      calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell
      adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI
      also induced phosphorylation of extracellular regulated protein kinases 1 and 2
      (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded
      calpain activation triggered by estrogenic and antiestrogenic stimulations
      indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or
      ICI-induced cell adhesion was dramatically impaired by calpain-specific
      inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30
      associated action. These data show that enhanced cell adhesion by E2 and ICI
      occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that
      targeting the GPR30 signaling may be a potential strategy to reduce metastasis
      and improve the efficacy of antiestrogens in treatment of advanced breast cancer.

PMID- 24440570
TI  - Hyperleucinemia causes hippocampal retromer deficiency linking diabetes to
      Alzheimer's disease.
AB  - Type 2 diabetes (T2D) is a major risk factor for late-onset Alzheimer's disease
      (AD). A variety of metabolic changes related to T2D (e.g. hyperinsulinemia,
      hyperglycemia, and elevated branched-chain amino acids) have been proposed as
      mechanistic links, but the basis for this association remains unknown. Retromer
      dependent trafficking is implicated in the pathogenesis of AD, and two key
      retromer proteins, VPS35 and VPS26, are deficient in the hippocampal formation of
      AD patients. We characterized VPS35 levels in five different mouse models of
      T2D/obesity to identify specific metabolic factors that could affect retromer
      levels in the brain. Mouse models in which hyperleucinemia was present displayed
      hippocampus-selective retromer deficiency. Wild-type lean mice fed a high leucine
      diet also developed hippocampal-selective retromer deficiency, and neuronal-like
      cells grown in high ambient leucine had reduced retromer complex proteins. Our
      results suggest that hyperleucinemia may account, in part, for the association of
      insulin resistance/T2D with AD. 

PMID- 24440572
TI  - Inappropriate expression of hepcidin by liver congestion contributes to anemia
      and relative iron deficiency.
AB  - BACKGROUND: Anemia and relative iron deficiency (RID) are prevalent in patients
      with heart failure (HF). The etiology of anemia and RID in HF patients is
      unclear. Hepcidin expression may be closely related to anemia and RID in HF
      patients. Although hepcidin is produced mainly by the liver, and the most
      frequent histologic appearance of liver in HF patients is congestion, the
      influence of liver congestion (LC) on hepcidin production has not yet been
      investigated. We investigated whether hepcidin contributed to anemia and RID in
      rats with LC. METHODS AND RESULTS: LC was induced in rats by ligating the
      inferior vena cava and compared with bleeding anemia (BA) model induced by
      phlebotomy and hemolytic anemia (HA) model induced by injection of
      phenylhydrazine. BA and HA strongly suppressed expression of hepcidin in liver
      and so did not cause decrease in serum iron and transferrin saturation. However,
      hepcidin expression did not decrease in LC rats, which resulted in anemia and
      lower transferrin saturation. In addition, many cells with hemosiderin deposits
      were observed in the liver and spleen and not in the bone marrow, and this
      appeared to be related to suppression of hepcidin expression. Iron accumulated in
      hepatocytes, and bone morphogenetic protein 6, which induces hepcidin, increased.
      Inflammation was observed in the congestive liver, and there was an increase in
      interleukin-6, which also induced hepcidin and was induced by free heme and
      hemoglobin via Toll-like receptor 4. CONCLUSIONS: We conclude that LC contributes
      to RID and anemia, and it does so via inappropriate expression of hepcidin.

PMID- 24440571
TI  - Resting state functional connectivity of the nucleus accumbens in youth with a
      family history of alcoholism.
AB  - Adolescents with a family history of alcoholism (FHP) are at heightened risk for
      developing alcohol use disorders (AUDs). The nucleus accumbens (NAcc), a key
      brain region for reward processing, is implicated in the development of AUDs.
      Thus, functional connectivity of the NAcc may be an important marker of risk in
      FHP youth. Resting state functional magnetic resonance imaging (rs-fcMRI) was
      used to examine the intrinsic connectivity of the NAcc in 47 FHP and 50 family
      history negative (FHN) youth, ages 10-16 years old. FHP and FHN adolescents
      showed significant group differences in resting state synchrony between the left
      NAcc and bilateral inferior frontal gyri and the left postcentral gyrus (PG).
      Additionally, FHP youth differed from FHN youth in right NAcc functional
      connectivity with the left orbitofrontal cortex (OFC), left superior temporal
      gyrus, right cerebellum, left PG, and right occipital cortex. These results
      indicate that FHP youth have less segregation between the NAcc and executive
      functioning brain regions, and less integration with reward-related brain areas,
      such as the OFC. The findings of the current study highlight that premorbid
      atypical connectivity of appetitive systems, in the absence of heavy alcohol use,
      may be a risk marker in FHP adolescents. 

PMID- 24440573
TI  - Clinical trial design in contemporary device studies in heart failure: is there a
      gold standard?
AB  - The assessment of the efficacy and safety of implantable cardiac devices used for
      the management of heart failure is complicated by procedural challenges. We
      present an overview of the advantages and disadvantages of different clinical
      trial designs, and discuss investigator and patient blinding. We conclude that
      blinding is optimal, but methodologically difficult. Until rules for and
      assessment of blinding are developed or surrogate measures are considered to be
      acceptable from a regulatory standpoint, an open-label design with objective end
      points is an unavoidable default standard. 

PMID- 24440574
TI  - Functional mitral regurgitation: therapeutic strategies for a ventricular
      disease.
AB  - Functional mitral regurgitation is a highly prevalent condition among patients
      with ischemic and dilated cardiomyopathies. Arising from remodeling of both the
      mitral valve annulus and the left ventricle, it is associated with high mortality
      and morbidity. In selected patients, cardiac resynchronization therapy helps to
      reduce functional mitral regurgitation, but surgical intervention remains the
      mainstay of therapy when medical therapy for left ventricular dysfunction has
      been inadequate. It is, however, associated with significant perioperative risks
      and does not alter long-term mortality. Percutaneous devices, and more recently
      the Mitraclip in particular, represent a promising alternative that can improve
      symptoms and ventricular remodeling with significantly lower periprocedural risk.

PMID- 24440575
TI  - Ligand-dependent stabilization of androgen receptor in a novel mouse ST38c
      Sertoli cell line.
AB  - Mature Sertoli cells (SC) are critical mediators of androgen regulation of
      spermatogenesis, via the androgen receptor (AR) signaling. Available immortalized
      SC lines loose AR expression or androgen responsiveness, hampering the study of
      endogenous AR regulation in SC. We have established and characterized a novel
      clonal mouse immortalized SC line, ST38c. These cells express some SC specific
      genes (sox9, wt1, tjp1, clu, abp, inhbb), but not fshr, yet more importantly,
      maintain substantial expression of endogenous AR as determined by PCR,
      immunocytochemistry, testosterone binding assays and Western blots. Microarrays
      allowed identification of some (146) but not all (rhox5, spinlw1), androgen
      dependent, SC expressed target genes. Quantitative Real-Time PCR validated
      regulation of five up-regulated and two down-regulated genes. We show that AR
      undergoes androgen-dependent transcriptional activation as well as agonist
      dependent posttranslational stabilization in ST38c cells. This cell line
      constitutes a useful experimental tool for future investigations on the molecular
      and cellular mechanisms of androgen receptor signaling in SC function. 

PMID- 24440576
TI  - Fractionating the role of executive control in control over worry: a preliminary
      investigation.
AB  - Uncontrollable anxious thought characterizes a number of emotional disorders.
      Little is known, however, about the cognitive mechanisms that underlie the
      ability to control these thoughts. The present study investigated the extent to
      which two well-characterized executive control processes--working memory and
      inhibition--are engaged when an individual attempts to control worry.
      Participants completed a concurrent assessment of these processes while
      attempting to control personally-relevant worried and neutral thoughts. To
      examine the specificity of these effects to attempts to control worry, versus a
      residual "depletion" effect of having previously engaged in worry, a subset of
      participants completed the assessment without instructions to control their
      worried or neutral thoughts. Attempts to control worry engaged working memory and
      inhibition to a greater extent than did attempts to control neutral thought. This
      increased engagement was not explained solely by anxious affect, nor was it
      significantly associated with trait worry. Engagement did not differ by group,
      suggesting that executive control depletion by worry cannot be dismissed as an
      alternative explanation of these findings. These results highlight working memory
      and inhibition as potentially valuable constructs for deepening our understanding
      of the nature and treatment of worry and its control.

PMID- 24440577
TI  - Preferences and attitudes toward approaches to depression relapse/recurrence
      prevention among pregnant women.
AB  - Patient preferences are increasingly recognized as important in clinical research
      and the delivery of evidence based practice in psychology. Although the
      prevention of depressive relapse/recurrence among perinatal women is an important
      public health goal, little is known about pregnant women's preferences and
      attitudes toward relapse/recurrence prevention interventions. Such information is
      important given low rates of care seeking among this population, and the
      potential for a relapse/recurrence prevention to avert negative outcomes among
      both vulnerable women and their offspring. Pregnant women seeking routine
      prenatal care in obstetric clinics (n = 200) were surveyed to assess their
      preferences for and attitudes about psychotherapy and pharmacological approaches
      to relapse/recurrence prevention. Women preferred psychotherapy (mindfulness
      based cognitive therapy and interpersonal therapy) more so than pharmacotherapy
      and reported significantly more favorable perceptions of the psychotherapy as
      compared to pharmacotherapy approaches to depression relapse/recurrence
      prevention. Results suggest also that depression history is important to consider
      in evaluating women's preferences and attitudes. Clinical and research
      implications of these findings are discussed. 

PMID- 24440579
TI  - [Introduction of a traceability system in the pharmacy oncology area in a
      tertiary hospital].

PMID- 24440578
TI  - Factor analyses of the Oral Health Impact Profile - overview and studied
      population.
AB  - PURPOSE: A desideratum of oral health-related quality of life (OHRQoL)
      instruments - such as the Oral Health Impact Profile (OHIP) - is that they
      accurately reflect the structure of the measured construct(s). With this goal in
      mind, the Dimensions of Oral Health-Related Quality of Life (DOQ) Project was
      proposed to investigate the number and nature of OHRQoL dimensions measured by
      OHIP. In this report, we describe our aggregate data set for the factor analyses
      in the project, which consists of responses to the 49-item OHIP from general
      population subjects and prosthodontics patients from 6 countries, including a
      large age range of adult subjects and both genders. MATERIALS AND METHODS: The
      DOQ Project's aggregate data set combines data from 35 individual studies
      conducted in Croatia, Germany, Hungary, Japan, Slovenia, and Sweden. RESULTS: The
      combined data set includes 10778 OHIPs from 9348 individuals (N=6349 general
      population subjects, N=2999 prosthodontic patients). To elucidate the OHIP latent
      structure, the aggregated data were split into a Learning Sample (N=5173) for
      exploratory analyses and a Validation Sample (N=5022) for confirmatory analyses.
      Additional data (N=583) were assigned to a third data set. CONCLUSION: The
      Dimensions of Oral Health-Related Quality of Life Project contains a large amount
      of international data and is representative of populations where OHIP is intended
      to be used. It is well-suited to assess the dimensionality of the questionnaire.

PMID- 24440580
TI  - [Classification and monitoring of the appropriateness of emergency admissions in
      a tertiary hospital].
AB  - OBJECTIVE: To measure the appropriateness of hospital admissions, to classify its
      Clinical Services (CS) according to the level of inappropriateness, and to
      determine the usefulness of applying rapid assessment techniques (lot quality
      assurance sampling) in these types of measurements. MATERIAL AND METHODS: A
      descriptive, retrospective study was conducted in a tertiary hospital to assess
      the clinical records of emergency admissions to the 12 CS with a higher volume of
      admissions, using the Appropriateness Evaluation Protocol (AEP). A four-level
      ("A" to "D") increasingly inadequate admissions scale was constructed setting
      both standard and threshold values in every stratum. Every CS was classified in
      one of them using lot quality assurance sampling (LQAS). A total of 156 cases (13
      cases from every CS) were assessed. The assessment effort (devoted time) was also
      estimated. RESULTS: There were 22.4+/-6.3% of inadequate admissions. In the CS
      classification, 9 (75%) got a good or acceptable appropriateness level, and only
      1 (8%) got an inacceptable level. The time devoted was estimated at 17 hours.
      CONCLUSIONS: AEP is useful to assess the admission appropriateness and may be
      included in the "Emergencies" process management, although its variability
      prevents the use for external comparisons. If both LQAS and the appropriateness
      classification level and the global estimation (by unifying lot samples) are
      combined, the monitoring is affordable without a great effort. To extend these
      tools to other quality indicators requiring direct observation or clinical
      records, manual assessment could improve the monitoring efficiency.

PMID- 24440581
TI  - [Problems in the transmission of information during within-hospital medical
      consultations and referrals].
AB  - OBJECTIVE: Within-hospital medical consultations and referrals (MCR) have many
      problems, among them are those related to the oral and written transmission of
      information. Our aim is to analyze problems in the transmission of information
      related to MCR, and possible differences between medical (MS) and surgical (SS)
      services. MATERIAL AND METHODS: A prospective, observational study was conducted
      on the MCR requested to Internal Medicine Service over an 8 month period. The
      following variables were collected: age, sex, the requester, MCR type, type of
      admission, comorbidity, hospital stay and mortality, length of MCR, the number of
      physicians responsible for the patient requesting service during the MCR, MCR
      repeats, information on the request, available medical records, verbal contact,
      conflict between doctors, and medical information in the discharge summary.
      RESULTS: Of the total 215 MCR received, 66 (30.7%) were requested by MS, and 149
      (69.3%) per SS. MCR duration was 3 days (standard deviation [SD] 4.8. The number
      of doctors responsible was 1.7 (SD 1.1), with, Repeats 43 (20%) and Urgent 14
      (6.5%). Minimum information on the request, 6 (9.1%) MS and 21 (27.5%) SS. Low
      availability of medical record, 2 (3%) MS and 50 (33.6%) SS. No verbal contact,
      33 (15.4%). Conflict between doctors 13 (6%). Information acceptably good in MCR
      urgent request 100% MS, and 80% SS. Two out of three MCR were without reference
      to the discharge report. CONCLUSIONS: There are significant losses in the
      transmission of information during the process of the MCR, which is higher in
      surgical than in medical departments.

PMID- 24440582
TI  - Small molecule interaction with lipid bilayers: a molecular dynamics study of
      chlorhexidine.
AB  - Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is
      thought to be the disruption of the cell membrane. We tested the capability of
      the Slipids all atom force fields using data from neutron scattering and NMR
      experiments on the drug chlorhexidine in a 1,2-dimyrisoyl-3-sn
      phosphatidylcholine (DMPC) membrane. Since it is not known what the charge of the
      CHX molecule is inside an apolar environment, a neutral, as well as a +1 and +2
      charge model for the molecule were created and tested at several concentrations.
      This study shows that the location of CHX is minorly dependent on concentration,
      and dominantly reliant on the charge. The effect of adding CHX to DMPC is a
      thinning of the membrane, thus increasing the area per lipid. 

PMID- 24440583
TI  - Detection of activated platelets in a mouse model of carotid artery thrombosis
      with 18 F-labeled single-chain antibodies.
AB  - INTRODUCTION: Activated platelets are key players in thrombosis and inflammation.
      We previously generated single-chain antibodies (scFv) against ligand-induced
      binding sites (LIBS) on the highly abundant platelet glycoprotein integrin
      receptor IIb/IIIa. The aim of this study was the construction and
      characterisation of a novel (18)F PET radiotracer based on this antibody.
      METHODS: ScFv(anti-LIBS) and control antibody mut-scFv were reacted with N
      succinimidyl-4-[(18)F]fluorobenzoate (S[(18)F]FB). Radiolabeled scFv was
      incubated with in vitro formed platelet clots and injected into mice with FeCl(3)
      induced thrombus in the left carotid artery. Clots were imaged in the PET scanner
      and amount of radioactivity measured using an ionization chamber and image
      analysis. Assessment of vessel injury as well as the biodistribution of the
      radiolabeled scFv was studied. RESULTS: After incubation with increasing
      concentrations of (18)F-scFv(anti-LIBS) clots had retained significantly higher
      amounts of radioactivity compared to clots incubated with radiolabeled (18)F-mut
      scFv (13.3 +/- 3.8 vs. 3.6 +/- 1 KBq, p < 0.05, n = 9, decay corrected). In the
      in vivo experiments we found an high uptake of the tracer in the injured vessel
      compared with the non-injured vessel, with 12.6 +/- 4.7% injected dose per gram
      (ID/g) uptake in the injured vessel and 3.7 +/- 0.9% ID/g in the non-injured
      vessel 5 minutes after injection (p < 0.05, n = 6). CONCLUSIONS: Our results show
      that the novel antibody radiotracer (18)F-scFv(anti-LIBS) is useful for the
      sensitive detection of activated platelets and thrombosis. ADVANCES IN KNOWLEDGE
      AND IMPLICATIONS FOR PATIENT CARE: We describe the first (18)F variant of a
      scFv(anti-LIBS) against activated platelets. This diagnostic agent could provide
      a powerful tool for the assessment of acute thrombosis and inflammation in
      patients in the future.

PMID- 24440584
TI  - Radiolabeling of HTE1PA: A new monopicolinate cyclam derivative for Cu-64
      phenotypic imaging. In vitro and in vivo stability studies in mice.
AB  - INTRODUCTION: HTE1PA, a monopicolinate-N-alkylated cyclam-based ligand has
      previously demonstrated fast complexation process, high kinetic inertness and
      important thermodynamic and electrochemical stability with respect to natural
      copper. In this work we first developed a new synthetic route to obtain HTE1PA in
      good yields. Then, we investigated HTE1PA chelation properties towards copper-64
      and assessed in vitro and in vivo stability of the resulting compound. METHODS:
      Radiolabeling of HTE1PA with copper-64 was tested at different ligand
      concentrations in ammonium acetate medium. In vitro stability study was carried
      out by incubating [(64)Cu]TE1PA complex in human serum at both 37 degrees C and 4
      degrees C; chromatographic controls were performed over 24h. Biodistribution,
      pharmacokinetic and hepatic metabolism of [(64)Cu]TE1PA were conducted in BALC/c
      mice in comparison with [(64)Cu]acetate and [(64)Cu]DOTA, used as a reference
      ligand. RESULTS: The promising results obtained for natural copper complexation
      were confirmed. HTE1PA was quantitatively radiolabeled in 15 min at room
      temperature. The resulting complex showed high serum stability. [(64)Cu]TE1PA
      induced a significant uptake in the liver and kidneys at early biodistribution
      time point. Nevertheless, a high speed wash out was observed at 24h leading to
      significantly lower uptake into the liver compared to [(64)Cu]DOTA. The
      metabolism study was consistent with a high resistance to transchelation as the
      initial uptake into liver matches with the intact form of [(64)Cu]TE1PA.
      CONCLUSION: Despite the partial elimination of HTE1PA - as copper-64 complex -
      through the hepatic route, its high selectivity for copper and its resistance to
      transchelation make it a promising ligand for antibody radiolabeling with either
      copper-64 or copper-67.

PMID- 24440585
TI  - Metacognitive therapy in people with a schizophrenia spectrum diagnosis and
      medication resistant symptoms: a feasibility study.
AB  - BACKGROUND AND OBJECTIVES: Cognitive behaviour therapy (CBT) for psychosis has
      been shown to be effective, but there are recent suggestions that it is less
      efficacious than initially thought. Metacognitive therapy (MCT), which focuses on
      metacognitive mechanisms, has led to positive results in other disorders, but has
      yet to be evaluated in people with schizophrenia spectrum diagnoses. This study
      evaluates the feasibility of MCT for people with psychotic disorders. METHODS:
      Ten participants with schizophrenia spectrum disorders received up to 12 sessions
      of MCT in an open trial. Outcomes included psychiatric symptoms measured using
      the PANSS, at baseline, 9 months (end of treatment) and at 12 months (follow-up),
      as well as dimensions of hallucinations and delusions, emotional dysfunction,
      self-rated recovery, social functioning and metacognitive beliefs. RESULTS: T
      tests and Wilcoxon's signed ranks tests revealed significant beneficial effects
      on several outcomes at end-of-treatment and follow-up. Cohen's d effect sizes
      were moderate to large (for PANSS total, d = 1.0 at end of treatment; d = 0.95 at
      follow-up). A response rate analysis found 50% and 40% of participants achieved
      at least a 25% reduction in PANSS total scores by end of therapy and follow-up,
      respectively. Exploratory analyses revealed that metacognitive beliefs
      significantly changed over treatment and follow-up periods. LIMITATIONS: This
      study had no control group and was not randomised; therefore, it is likely that
      effect sizes were inflated. CONCLUSIONS: This study provides preliminary evidence
      that MCT is a feasible treatment for people with psychosis. An adequately powered
      randomised controlled trial is warranted.

PMID- 24440586
TI  - Association of methylenetetrahydrofolate reductase (A1298C and C677T)
      polymorphisms with retinal vein occlusion in Tunisian patients.
AB  - The role of two polymorphisms C677T and A1298C of the methylenetetrahydrofolate
      reductase (MTHFR) gene in the etiology of retinal vein occlusion (RVO) has not
      been adequately clarified. The aim of this study was to examine the prevalence of
      these polymorphisms among RVO Tunisian patients with and without systemic risk
      factors. Seventy-two patients with retinal vein occlusion (RVO) were studied. The
      control group included140 people matched for age, sex, and risk factors.
      Participants in the study were genotyped for the MTHFR C677T and A1298C
      polymorphisms. The genotyping was performed by PCR-RFLP. No significant
      differences were found in the frequencies of the three genotypes (AA, AC, CC) of
      the MTHFR A1298C polymorphism between RVO patients and healthy controls. However,
      the prevalence of the group of mutated genotypes (AC+CC) of the missense variant
      MTHFR A1298C was significantly different between patients and controls (16.67%
      vs. 6.42%, p=.01). Additionally, the frequency of the CT genotype as well as the
      group of combined mutated genotypes (CT+TT) for the C677T variant was
      significantly higher among RVO patients compared with controls (p<10(-3), p<10(
      3)). This suggests an association between this polymorphism and RVO. Large study
      populations would be required to understand more completely the contribution of
      these markers in the risk of RVO. 

PMID- 24440587
TI  - Unpacking the 'information barrier': comparing perspectives on information as a
      barrier to climate change adaptation in the interior mountain West.
AB  - Inadequate information has been repeatedly identified as a barrier to climate
      change adaptation planning and implementation. However less is known about how
      information functions as a barrier, and to what degree it prevents adaptation
      compared to other perceived barriers. In addition, the role of institutional
      context in mediating the demand for information in the context of adaptation has
      been less well studied. This paper helps to clarify the role that information
      plays in adaptation planning for two sectors of public employees working at
      similar scales, in similar locations, with similar challenges. We conducted
      surveys and semi-structured interviews to investigate the demand for information
      in support of adaptation implementation and planning from US federal public lands
      managers and municipal officials in the US interior West. We found that federal
      managers and municipal officials both consulted information frequently for
      decision making, and while both groups indicated that lack of information at
      relevant scales was a barrier to adaptation planning, this was seen as a much
      stronger barrier for federal managers than for communities. Uncertainty of
      information was raised as an issue, but results were mixed on whether or not this
      acted as a strong barrier. While peer-reviewed publications were seen as the
      "best available science," and correlated with adaptation planning, they were not
      accessed directly as frequently as other sources of information, including
      colleagues, the internet and reports. The strong connection between communities
      and adjacent federal lands may provide an opportunity for networking that could
      facilitate the flow of information relevant for adaptation. 

PMID- 24440588
TI  - Isomorphism and disorder in o-chlorohalobenzenes studied by NQR.
AB  - In this work we present experimental results that allow to characterize different
      solid modifications found in o-chlorohalobenzenes. Three disordered phases have
      been found in o-chlorobromobenzene. The stable phase at high temperature (phase
      I) is also obtained by quenching the sample at 77 K. Slow cooling allow to obtain
      the low temperature phase III which, on heating, transforms to phase II at 183 K
      and this, in turns, transforms to phase I at T~210 K. The disorder evidenced
      through the Nuclear Quadrupole Resonance spectra, is attributed to a random
      occupation of chlorine and bromine sites. In all phases there is evidence of
      molecular reorientations out of the benzene ring plane around the pseudo-symmetry
      axis between the atoms of Cl and Br. In o-chlorofluorobenzene two phases have
      been found depending on the cooling rate. One phase is disordered due to the
      random exchange of the occupation of Cl and F sites. In this case, there is also
      evidence of molecular reorientations out of the benzene ring plane, but in this
      case the reorientation is around the pseudo-symmetry axis that pass through the C
      Cl bonds. Comparisons with the behavior of o-dichlorobenzene are also made.

PMID- 24440589
TI  - Does computed tomographic scan affect diagnosis and management of patients with
      suspected renal colic?
AB  - BACKGROUND: Patients with renal colic commonly present to the emergency
      department (ED) and are usually treated with analgesics, antiemetics and
      hydration. Computed tomographic (CT) scan is commonly utilized in evaluating
      patients with suspected renal colic. OBJECTIVES: We compared diagnosis and
      treatment plans before and after CT in patients with suspected renal colic with
      the aim to evaluate how often changes in diagnosis, treatment and disposition are
      made. METHODS: In this prospective observational study, we enrolled a convenience
      sample of clinically Stable ED patients older than 17 with suspected renal colic
      for whom CT was planned. Exclusion criteria were: chronic kidney disease, urinary
      tract infection, recent CT and history of previous kidney stone. Pre-CT and Post
      CT surveys were completed by the treating provider. RESULTS: The discharge
      diagnosis was renal colic in 62 of 93 enrolled patients (67%). Urinalysis showed
      blood in 52 of these patients (84%). CT confirmed obstructing kidney or bladder
      stone in 50 patients. There were five cases of alternative diagnoses noted on CT
      scan. After CT scan, 7 patients had changes in disposition. Sixteen providers
      felt that CT would not change management. In these cases, CT offered no
      alternative diagnosis and didn't change disposition. CONCLUSION: CT scan didn't
      change management when providers did not expect it would. This indicates that
      providers who are confident with the diagnosis of renal colic should consider
      forgoing a CT scan. CT scan did occasionally find important alternative diagnoses
      and should be utilized when providers are considering other concerning pathology.

PMID- 24440590
TI  - Anaerobiospirillum succiniciproducens-induced bacteremia in a healthy man.
AB  - Anaerobiospirillum succiniciproducens is rarely associated with bacteremia but
      results in significant mortality. Almost all reported bacteremia cases have
      occurred in immunocompromised hosts, such as those with alcoholic liver disease,
      atherosclerosis, recent surgery, malignancies, or acquired immunodeficiency
      syndrome. We describe here, to our knowledge, the first clinical evidence for A
      succiniciproducens bacteremia in a healthy man. A 61-year-old man had fallen from
      a roof and was admitted to our emergency department with severe left flank pain
      without an external wound. He was given transcatheter arterial embolization for
      the left kidney injury on the same day, and his condition stabilized. Four days
      after admission, he had fever without gastrointestinal signs and symptoms. Spiral
      shaped, gram-negative anaerobic bacteria were isolated from 2 sets of blood
      cultures, and the oxidase and catalase test results were negative. The isolated
      bacteria were different from the Campylobacter spp. On the next day, the bacteria
      were confirmed as A succiniciproducens by 16S rRNA sequencing. The patient
      responded to sulbactam/ampicillin. On day 13, the patient was discharged with a 7
      day prescription for oral amoxicillin/clavulanate. Six months after admission,
      the patient was free of recurrent infection. A succiniciproducens bacteremia can
      occur in healthy adults. When large gram-negative spiral-shaped bacteria are
      detected, this bacterial species should be considered and differentiated from the
      Campylobacter spp because A succiniciproducens is often resistant to macrolide
      antibiotics.

PMID- 24440591
TI  - Use of an intraosseous device for invasive pressure monitoring in the ED.
AB  - Venous access is essential to providing emergency care for critically ill or
      injured patients. Obtaining peripheral or central access can be problematic and
      time consuming. Intraosseous (IO) fluid administration provides similar flow
      rates and central circulation times compared to central lines, but use of these
      devices to monitor blood pressure has not been explored. We report a case of
      successful IO pressure (IOP) monitoring through an IO during the resuscitation of
      a 31-year-old male. This is the first report of monitoring IOP in a clinical
      setting and comparing it to traditional measures of central pressure.

PMID- 24440592
TI  - Plasticity and conformational equilibria of influenza fusion peptides in model
      lipid bilayers.
AB  - Membrane fusion is critical to eukaryotic cellular function and crucial to the
      entry of enveloped viruses such as influenza and human immunodeficiency virus.
      Influenza viral entry in the host cell is mediated by a 20-23 amino acid long
      sequence, called the fusion peptide. In the last years, possible structures for
      the fusion peptide and their implication in the membrane fusion initiation have
      been proposed; these ranging from an inverted V shaped alpha-helical structure to
      an alpha-helical hairpin, or to a complete alpha-helix. Here we develop a coarse
      grained approach to describe effectively the plasticity of the fusion peptide and
      the explored conformational states. We describe also a trimeric assembly for the
      fusion peptide and analyse the explored states in a 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine model membrane. For the single fusion peptide systems
      the kink angle observed experimentally for the V shaped structure shows a strong
      correlation with the orientation of the fusion peptide within the lipid bilayer.
      The trimeric fusion peptide model also experiences different conformational
      states and represents a more realistic model for the anchoring mechanism of one
      influenza haemagglutinin molecule. This article is part of a Special Issue
      entitled: Viral Membrane Proteins - Channels for Cellular Networking. 

PMID- 24440593
TI  - Neuroprotective effects of PEP-1-carbonyl reductase 1 against oxidative-stress
      induced ischemic neuronal cell damage.
AB  - Human carbonyl reductase 1 (CBR1) is a member of the NADPH-dependent short-chain
      dehydrogenase/reductase superfamily that is known to play an important role in
      neuronal cell survival via its antioxidant function. Oxidative stress is one of
      the major causes of degenerative disorders including ischemia. However, the role
      CBR1 plays with regard to ischemic injury is as yet poorly understood. Protein
      transduction domains such as PEP-1 are well known and now commonly used to
      deliver therapeutic proteins into cells. In this study, we prepared PEP-1-CBR1
      protein and examined whether it protects against oxidative-stress-induced
      neuronal cell damage. PEP-1-CBR1 protein was efficiently transduced into
      hippocampal neuronal HT-22 cells and protected against hydrogen peroxide (H2O2)
      induced neuronal cell death. Transduced PEP-1-CBR1 protein drastically inhibited
      H2O2-induced reactive oxygen species production, the oxidation of intracellular
      macromolecules, and the activation of mitogen-activated protein kinases, as well
      as cellular apoptosis. Furthermore, we demonstrated that transduced PEP-1-CBR1
      protein markedly protected against neuronal cell death in the CA1 region of the
      hippocampus resulting from ischemic injury in an animal model. In addition, PEP-1
      CBR1 protein drastically reduced activation of glial cells and lipid peroxidation
      in an animal model. These results indicate that PEP-1-CBR1 protein significantly
      protects against oxidative-stress-induced neuronal cell death in vitro and in
      vivo. Therefore, we suggest that PEP-1-CBR1 protein may be a therapeutic agent
      for the treatment of ischemic injuries as well as oxidative-stress-induced cell
      damage and death. 

PMID- 24440594
TI  - Nrf2 signaling modulates cigarette smoke-induced complement activation in retinal
      pigmented epithelial cells.
AB  - Whereas cigarette smoking (CS) and dysregulated complement are thought to play
      central roles in age-related macular degeneration (AMD), their exact roles are
      unknown. The aim of this study was to determine if CS activates complement and if
      the antioxidant transcription factor Nrf2 modulates this response. In AMD
      specimens, Nrf2 immunolabeling was strong in the cytoplasm, with scattered
      nuclear labeling of macular retinal pigmented epithelial (RPE) cells that
      appeared normal, but was decreased and without nuclear labeling in dysmorphic
      cells overlying drusen, a hallmark AMD lesion. Cigarette smoke extract (CSE)
      induced Nrf2 nuclear translocation in RPE cells with increased antioxidant and
      complement gene expression. Whereas CFH protein was not altered by CSE, the cell
      membrane regulator proteins CD46, CD55, and CD59 were decreased, and C3a and C3b,
      but not iC3b, were increased compared to controls. C5b-9 was increased by CSE,
      but at sublytic levels, only after addition of normal human serum. Nrf2 knockdown
      enhanced the increase in C3a and C3b from CSE, but not iC3b, C5a, or C5b-9. CSE
      also increased IL-1b expression and secretion after C3a generation and was
      reduced by a C3aR antagonist. In contrast, the Nrf2 activator CDDO-Im restored
      complement gene expression in RPE cells exposed to CSE. We provide evidence of
      altered Nrf2 in human AMD and that CSE induces a proinflammatory environment
      specifically by generating C3a and C3b, and Nrf2 deficiency magnifies this
      specific complement response. 

PMID- 24440596
TI  - Executive function in posttraumatic stress disorder (PTSD) and the influence of
      comorbid depression.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with
      neurocognitive deficits, such as impaired verbal memory and executive
      functioning. Less is known about executive function and the role of comorbid
      depression in PTSD. Recently, studies have shown that verbal memory impairments
      may be associated with comorbid depressive symptoms, but their role in executive
      function impairments is still unclear. OBJECTIVE: To examine several domains of
      executive functioning in PTSD and the potentially mediating role of comorbid
      depressive symptoms in the relationship between executive function and PTSD.
      METHOD: Executive functioning was assessed in 28 PTSD patients and 28 matched
      trauma-exposed controls. The Cambridge Neuropsychological Test Automated Battery
      (CANTAB) with subtests measuring response inhibition (SST), flexibility/set
      shifting (IED), planning/working memory (OTS) and spatial working memory (SWM)
      was administered in PTSD patients and trauma-exposed controls. Regression
      analyses were used to assess the predictive factor of PTSD symptoms (CAPS) and
      depressive symptoms (HADS-D) in relation to executive function when taking into
      account the type of trauma. Pearson's correlations were used to examine the
      association between PTSD symptom clusters (CAPS) and executive function. The
      mediating effects of depression and PTSD were assessed using regression
      coefficients and the Sobel's test for mediation. RESULTS: Our findings indicate
      that PTSD patients performed significantly worse on executive function than
      trauma-exposed controls in all domains assessed. PTSD symptoms contributed to
      executive functioning impairments (SST median correct, IED total errors, OTS
      latency to correct, SWM total errors and SWM strategy). Adding depressive
      symptoms to the model attenuated these effects. PTSD symptom clusters 'numbing'
      and to a lesser extent 'avoidance' were more frequently associated with worse
      executive function (i.e., IED total errors, OTS latency to correct and SWM total
      errors) than 'reexperiencing' and 'hyperarousal'. Depressive symptoms mediated
      the relation between PTSD and executive function on some executive function
      measures (IED total errors and OTS latency to correct), whereas PTSD did not
      mediate the relation between depression and executive function. CONCLUSIONS: PTSD
      patients perform worse on executive function. The impairments seem to be mostly
      associated with the less specific PTSD symptom cluster of 'numbing'. Depressive
      symptoms seem to mediate the relationship between PTSD and executive function.
      These findings may have clinical implications with regard to treatment indication
      and prognosis.

PMID- 24440595
TI  - Corneal stromal stem cells versus corneal fibroblasts in generating structurally
      appropriate corneal stromal tissue.
AB  - Recapitulation of human corneal stromal tissue is believed to be among the most
      challenging steps in engineering human corneal tissue because of the difficulty
      in reproducing its highly-ordered hierarchical ultrastructure, which imparts its
      robust biomechanical properties and optical transparency. In this study, we
      compared the feasibility of utilizing human corneal stromal stem cells (hCSSCs)
      and human corneal fibroblasts (hCFs) in the generation of human corneal stromal
      tissue on a highly-aligned fibrous substrate made from poly(ester urethane) urea.
      In the serum-free keratocyte differentiation medium supplemented with FGF-2 (10
      ng/mL) and TGF-beta3 (0.1 ng/mL), hCSSCs successfully differentiated into
      keratocytes and secreted multilayered lamellae with orthogonally-oriented
      collagen fibrils, in a pattern mimicking human corneal stromal tissue. The
      constructs were 60-70 MUm thick and abundant in cornea-specific extracellular
      matrix (ECM) components, including keratan sulfate, lumican, and keratocan. Under
      the identical conditions, hCFs tended to differentiate into myofibroblasts and
      deposited a less-organized collagen-fibrillar construct in a pattern with
      similarities to corneal scar tissue due to a lack of cornea-specific ECM
      components. These observations demonstrated that hCSSCs showed a much greater
      potential, under proper substrate and growth factor guidance, to facilitate the
      generation of a biological human cornea equivalent. Unlike hCSSCs, hCFs were less
      responsive to these environmental cues and under identical culture conditions
      generated an ECM that poorly mimicked the native, functional tissue structure and
      composition. 

PMID- 24440597
TI  - Using distraction to regulate emotion: insights from EEG theta dynamics.
AB  - Distraction is a powerful and widely-used emotion regulation strategy. Although
      distraction regulates emotion sooner than other cognitive strategies
      (Thiruchselvam, Blechert, Sheppes, Rydstrom, & Gross, 2011), it is not yet clear
      whether it is capable of blocking the earliest stages of emotion generation. To
      address this issue, we capitalized on the excellent temporal resolution of EEG by
      focusing on occipital theta dynamics which were associated with distinct stages
      of visual processing of emotional stimuli. Individually defined theta band
      dynamics were extracted from a previously published EEG dataset (Thiruchselvam et
      al., 2011) in which participants attended to unpleasant (and neutral) images or
      regulated emotion using distraction and reappraisal. Results revealed two peaks
      within early theta power increase, both of which were increased by emotional
      stimuli. Distraction did not affect theta power during an early peak (150-350
      ms), but did successfully decrease activity in a second peak (350-550 ms). These
      results suggest that although distraction acts relatively early in the emotion
      generative trajectory, it does not block fast detection of emotional
      significance. Given that theta dynamics were uncorrelated with Late Positive
      Potential activity, the present results also encourage researchers to add the
      occipital theta to the growing toolkit of EEG-based measures of emotion
      regulation.

PMID- 24440598
TI  - A few observations on linking VEP responses to the magno- and parvocellular
      systems by way of contrast-response functions.
AB  - It has been proposed that magno- and parvocellular contributions to Visually
      Evoked Potentials (VEPs) can be isolated, or differentiated, by noting the
      contrast-response relationships of the responses. This suggestion is examined
      quantitatively by determining the similarity between various sets of VEP data
      that have been attributed to the magno- and parvocellular systems and previously
      reported contrast-response functions for different kinds of neurons (magno- and
      parvocellular neurons and V1, V4, and MT cells) and combinations of the contrast
      response functions for these neurons. It is found that other neurons, or
      combinations of other neurons, typically give better fits to the data than do
      magno- and parvocellular cells. Thus, to attribute VEP responses to the magno- or
      parvocellular systems based on contrast-responses properties faces difficulties. 

PMID- 24440599
TI  - Proto-oncogenic role of mutant IDH2 in leukemia initiation and maintenance.
AB  - Mutations in the metabolic enzymes isocitrate dehydrogenase-1 (IDH1) and IDH2
      that produce the oncometabolite D-2-hydroxyglutarate (2-HG) occur frequently in
      human acute myeloid leukemia (AML). 2-HG modulates numerous biological pathways
      implicated in malignant transformation, but the contribution of mutant IDH
      proteins to maintenance and progression of AML in vivo is currently unknown. To
      answer this crucial question we have generated transgenic mice that express
      IDH2(R140Q) in an on/off- and tissue-specific manner using a tetracycline
      inducible system. We found that IDH2(R140Q) can cooperate with overexpression of
      HoxA9 and Meis1a and with mutations in FMS-like tyrosine kinase 3 (FLT3) to drive
      acute leukemia in vivo. Critically, we show that genetic deinduction of mutant
      IDH2 in leukemic cells in vivo has profound effects on their growth and/or
      maintenance. Our data demonstrate the proto-oncogenic role of mutant IDH2 and
      support its relevance as a therapeutic target for the treatment of human AML. 

PMID- 24440600
TI  - Clonal analysis via barcoding reveals diverse growth and differentiation of
      transplanted mouse and human mammary stem cells.
AB  - Cellular barcoding offers a powerful approach to characterize the growth and
      differentiation activity of large numbers of cotransplanted stem cells. Here, we
      describe a lentiviral genomic-barcoding and analysis strategy and its use to
      compare the clonal outputs of transplants of purified mouse and human basal
      mammary epithelial cells. We found that both sources of transplanted cells
      produced many bilineage mammary epithelial clones in primary recipients, although
      primary clones containing only one detectable mammary lineage were also common.
      Interestingly, regardless of the species of origin, many clones evident in
      secondary recipients were not detected in the primary hosts, and others that were
      changed from appearing luminal-restricted to appearing bilineage. This barcoding
      methodology has thus revealed conservation between mice and humans of a
      previously unknown diversity in the growth and differentiation activities of
      their basal mammary epithelial cells stimulated to grow in transplanted hosts. 

PMID- 24440601
TI  - Detection of toxic monofluoroacetate in Palicourea species.
AB  - Numerous plant species worldwide including some Palicourea (Rubiaceae), Tanaecium
      (Bignoniaceae), and Amorimia (Malpighiaceae) species in Brazil cause sudden death
      and are known to contain monofluoroacetate (MFA). Two species of Palicourea,
      Palicourea aenofusca and Palicourea marcgravii, cause sudden death and are
      reported to contain MFA while other Palicourea species are reported to cause
      sudden death in livestock and are suspected to contain MFA due to the similarity
      in clinical signs. Using an HPLC-APCI-MS method to detect MFA, herbarium
      specimens representing 46 Palicourea taxa were screened for the presence of MFA.
      Additionally we screened five Psychotria taxa that are closely related to
      Palicourea species. Ten species of Palicourea were identified that contained MFA,
      two previously reported and eight newly reported here; these are closely related
      to each other, though some other related species did not contain MFA. 

PMID- 24440602
TI  - The ABC of BTC: structural properties and biological roles of betacellulin.
AB  - Betacellulin was initially detected as a growth-promoting factor in the
      conditioned medium of a mouse pancreatic beta-cell tumor cell line. Sequencing of
      the purified protein and of the cloned cDNA supported the assumption that
      betacellulin is a new ligand of the epidermal growth factor receptor (EGFR),
      which was later confirmed experimentally. As a typical EGFR ligand, betacellulin
      is expressed by a variety of cell types and tissues, and the soluble growth
      factor is proteolytically cleaved from a larger membrane-anchored precursor.
      Importantly, BTC can - in addition to the EGFR - bind and activate all possible
      heterodimeric combinations of the related ERBB receptors including the highly
      oncogenic ERBB2/3 dimer, as well as homodimers of ERBB4. While a large number of
      studies attest a role for betacellulin in the differentiation of pancreatic beta
      cells, the last decade witnessed the association of betacellulin with a large
      number of additional biological processes, ranging from reproduction to the
      control of neural stem cells. 

PMID- 24440603
TI  - Striated muscle laminopathies.
AB  - Lamins A and C, encoded by LMNA, are constituent of the nuclear lamina, a
      meshwork of proteins underneath the nuclear envelope first described as
      scaffolding proteins of the nucleus. Since the discovery of LMNA mutations in
      highly heterogeneous human disorders (including cardiac and muscular dystrophies,
      lipodystrophies and progeria), the number of functions described for lamin A/C
      has expanded. Lamin A/C is notably involved in the regulation of chromatin
      structure and gene transcription, and in the resistance of cells to mechanical
      stress. This review focuses on studies performed on knock-out and knock-in Lmna
      mouse models, which have led to decipher some of the lamin A/C functions in
      striated muscles and to the first preclinical trials of pharmaceutical therapies.

PMID- 24440604
TI  - Role of 2-hydroxyethyl methacrylate in the interaction of dental monomers with
      collagen studied by saturation transfer difference NMR.
AB  - OBJECTIONS: Functional adhesive monomers are formulated with solvents and
      hydrophilic resin monomers, such as 2-hydroxyethyl methacrylate (HEMA). In
      theory, exposed collagen fibrils should be covered and protected by the resin
      matrix. We examined if the atomic- and molecular-level interaction of monomers
      with collagen would be affected when the monomers are blended with HEMA. METHODS:
      We performed saturation transfer difference (STD) NMR spectroscopy to investigate
      the binding interaction of two functional monomers, 4-methacryloyloxyethyl
      trimellitic acid (4-MET) and 10-methacryloyloxydecyl dihydrogen phosphate (MDP),
      with atelocollagen as a triple-helical peptide model. The STD NMR measurement was
      performed by adding 4-MET or MDP to the atelocollagen solution. RESULTS: When the
      atelocollagen was saturated, the STD signals were detected in the MDP spectrum
      for the protons in the aliphatic chain when MDP was dissolved in DMSO. However,
      the STD signals disappeared when MDP was mixed with HEMA. No STD signal was
      visible for the 4-MET ligand samples in either DMSO or for the HEMA blend sample.
      DISCUSSION: The interaction of MDP with atelocollagen is hydrophobic; however,
      the MDP-HEMA blend may form an aggregate in the atelocollagen solution, which
      would suppress the hydrophobicity of MDP. The formation of the MDP-HEMA aggregate
      may compromise the MDP-collagen interaction, and leave the collagen fibrils
      unprotected by MDP and HEMA. Unstable chemical interaction of the monomers with
      the exposed collagen may deteriorate hybrid layer integrity and strong dentine
      bonding.

PMID- 24440605
TI  - Effect of BiodentineTM on the proliferation, migration and adhesion of human
      dental pulp stem cells.
AB  - OBJECTIVES: To investigate the proliferative, migratory and adhesion effect of
      BiodentineTM, a new tricalcium silicate cement formulation, on the human dental
      pulp stem cells (hDPSCs). METHODS: The cell cultures of hDPSCs obtained from
      impacted third molars were treated with BiodentineTM extract at four different
      concentrations: BiodentineTM 0.02mg/ml (BD 0.02), BiodentineTM 0.2mg/ml (BD 0.2),
      BiodentineTM 2mg/ml (BD 2) and BiodentineTM 20mg/ml (BD 20). Human dental pulp
      stem cells proliferation was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2, 5
      diphenyl-2H-tetrazolium bromide) and BrdU (5-bromo-2'-deoxyuridine) viability
      analysis at different times. Migration was investigated by microphotographs of
      wound healing and transwell migration assays. Adhesion assay was performed as
      well in presence of BD 0.2, BD 2 and blank control, while qRT-PCR (quantitative
      real-time reverse-transcriptase polymerase chain) was used for further analysis
      of the mRNA expression of chemokine and adhesion molecules in hDPSCs. RESULTS:
      BiodentineTM significantly increased proliferation of stem cells at BD 0.2 and BD
      2 concentrations while decreased significantly at higher concentration of BD 20.
      BD 0.2 concentration had a statistically significant increased migration and
      adhesion abilities. In addition, qRT-PCR results showed that BD 0.2 could have
      effect on the mRNA expression of chemokines and adhesion molecules in human
      dental pulp stem cells. CONCLUSIONS: The data imply that BiodentineTM is a
      bioactive and biocompatible material capable of enhancing hDPSCs proliferation,
      migration and adhesion abilities. CLINICAL SIGNIFICANCE: BiodentineTM when placed
      in direct contact with the pulp during pulp exposure can positively influence
      healing by enhancing the proliferation, migration and adhesion of human dental
      pulp stem cells.

PMID- 24440606
TI  - Physiologically based toxicokinetic modeling of secondary acute myelolytic
      leukemia.
AB  - Benzene, designated as environmental and occupational carcinogen and hematotoxin,
      has been associated with secondary leukemia. To develop a toxicokinetic model of
      AML, benzene can be used as leukemogenic agent. The aim of the present study was
      to optimize the dose, period and time of cumulative benzene exposure of Swiss
      Albino mice and to analyze survival rate; alteration in cell cycle regulation and
      other clinical manifestations in mice exposed to benzene vapour at a dose 300 ppm
      * 6 h/day * 5 days/week for 2 weeks, i.e., 9000(a)ppm cumulative dose. Analyzing
      physiological parameters like plasma enzyme profile, complete hematology (Hb %,
      RBC indices and WBC differentials), hematopoietic cells morphology, expression of
      cell cycle regulatory proteins, tissue histology and analysis of DNA
      fragmentation, optimum conditions were established. Down regulation of p53 and
      p21 and up regulation of CDK2, CDK4, CDK6, cyclin D1 and E in this exposed group
      were marked as the optimum conditions of cellular deregulation for the
      development of secondary AML. Elevated level of Plasma AST/ALT with corresponding
      changes in liver histology showing extended sinusoids within the hepatocytic cell
      cords in optimally exposed animals also confirmed the toxicokinetic relation of
      benzene with leukemia. It can be concluded from the above observations that the
      9000(a)ppm exposed animals can serve as the induced laboratory model of secondary
      acute myeloid leukemia.

PMID- 24440607
TI  - Crystal structures of d-alanine-d-alanine ligase from Xanthomonas oryzae pv.
      oryzae alone and in complex with nucleotides.
AB  - D-Alanine-D-alanine ligase (DDL) catalyzes the biosynthesis of d-alanyl-d
      alanine, an essential bacterial peptidoglycan precursor, and is an important drug
      target for the development of antibacterials. We determined four different
      crystal structures of DDL from Xanthomonas oryzae pv. oryzae (Xoo) causing
      Bacteria Blight (BB), which include apo, ADP-bound, ATP-bound, and AMPPNP-bound
      structures at the resolution between 2.3 and 2.0 A. Similarly with other DDLs,
      the active site of XoDDL is formed by three loops from three domains at the
      center of enzyme. Compared with d-alanyl-d-alanine and ATP-bound TtDDL structure,
      the gamma-phosphate of ATP in XoDDL structure was shifted outside toward
      solution. We swapped the omega-loop (loop3) of XoDDL with those of Escherichia
      coli and Helicobacter pylori DDLs, and measured the enzymatic kinetics of wild
      type XoDDL and two mutant XoDDLs with the swapped omega-loops. Results showed
      that the direct interactions between omega-loop and other two loops are essential
      for the active ATP conformation for D-ala-phosphate formation.

PMID- 24440609
TI  - Influence of heme environment structure on dioxygen affinity for the dual
      function Amphitrite ornata hemoglobin/dehaloperoxidase. Insights into the
      evolutional structure-function adaptations.
AB  - Sea worm, Amphitrite ornata, has evolved its globin (an O(2) carrier) also to
      serves as a dehaloperoxidase (DHP) to detoxify haloaromatic pollutants generated
      by competing species. A previous mutagenesis study by our groups on both DHP and
      sperm whale myoglobin (SW Mb) revealed some structural factors that influence the
      dehaloperoxidase activities (significantly lower for Mb) of both proteins. Using
      an isocyanide/O(2) partition constant measurement method in this study, we have
      examined the effects of these structural factors on the O(2) equilibrium
      constants (KO2) of DHP, SW Mb, and their mutants. A clear trend of decreasing
      O(2) affinity and increasing catalytic activity along with the increase in the
      distal His N(epsilon)-heme iron distance is observed. An H93K/T95H Mb double
      mutant mimicking the DHP proximal His positioning exhibited markedly enhanced
      O(2) affinity, confirming the essential effect of proximal His rotation on the
      globin function of DHP. For DHP, the L100F, T56G and M86E variants showed the
      effects of distal volume, distal His flexibility and proximal electronic push,
      respectively, on the O(2) affinity. This study provides insights into how DHP has
      evolved its heme environment to gain significantly enhanced peroxidase capability
      without compromising its primary function as an O(2) carrier.

PMID- 24440608
TI  - Candidate mediators of chondrocyte mechanotransduction via targeted and
      untargeted metabolomic measurements.
AB  - Chondrocyte mechanotransduction is the process by which cartilage cells transduce
      mechanical loads into biochemical and biological signals. Previous studies have
      identified several pathways by which chondrocytes transduce mechanical loads, yet
      a general understanding of which signals are activated and in what order remains
      elusive. This study was performed to identify candidate mediators of chondrocyte
      mechanotransduction using SW1353 chondrocytes embedded in physiologically stiff
      agarose. Dynamic compression was applied to cell-seeded constructs for 0-30min,
      followed immediately by whole-cell metabolite extraction. Metabolites were
      detected via LC-MS, and compounds of interest were identified via database
      searches. We found several metabolites which were statistically different between
      the experimental groups, and we report the detection of 5 molecules which are not
      found in metabolite databases of known compounds indicating potential novel
      molecules. Targeted studies to quantify the response of central energy
      metabolites to compression found a transient increase in the ratio of NADP+ to
      NADPH and a continual decrease in the ratio of GDP to GTP, suggesting a flux of
      energy into the TCA cycle. These data are consistent with the remodeling of
      cytoskeletal components by mechanically induced signaling, and add substantial
      new data to a complex picture of how chondrocytes transduce mechanical loads. 

PMID- 24440610
TI  - Oral colonization: a possible source for candidemia in low-weight neonates.
AB  - OBJECTIVE: To check the oral colonization in neonates at high-risk and to
      associate these cases with candidemia. SUBJECTS AND METHODS: This study was
      conducted in the NICU. For six months, 125 high-risk neonates were investigated
      for oral colonization and septicemia by yeasts. From this total, 19 neonates had
      yeasts on the oral mucosae and 12 neonates developed fungemia. All of the 12
      neonates with fungemia were included in the amount of 19 who have presented oral
      colonization by yeasts. RESULTS: There was a species concordance between the
      yeasts of the oral mucosae and the blood in 6 neonates (50%) among the 12
      neonates with oral colonization and septicemia at the same time. The yeasts
      isolated in these 6 cases regarding the species concordance were Candida albicans
      (5 cases, 83.4%) and Candida parapsilosis (1 case, 16.6%). All of the cases
      involving an association were confirmed by PFGE. All of the strains of yeasts
      involved in oral colonization and also blood presented the same karyotype. A
      total of 66.6% of the patients with strains in agreement progressed to death.
      CONCLUSION: The results indicate the relevance of monitoring the oral microbiota,
      as a possible source of fungal infection, and assisting to develop appropriate
      therapeutic strategy.

PMID- 24440611
TI  - [Rhinofacial conidiobolomycosis associated with cervical, thoracic and brachial
      localizations: one clinical case in Nigeria].
AB  - We report here the clinical case of a Nigerian adult patient who received medical
      care during October 2010, at the Center for Diagnosis and Treatment of Buruli
      ulcer in Pobe (Benin). He presented a massive facial tumor associated with
      several subcutaneous (cervical, thoracic and upper limbs) nodules, evolving since
      several years. Tissue samples collected at Pobe medical center were addressed to
      the mycology and histology laboratories of Angers University Hospital (France),
      according to the medical exchange agreement between the two institutions about
      the diagnosis and treatment of Buruli ulcer disease. Histological examination
      showed a Splendore-Hoeppli phenomenon, consisting of a granulomatous reaction
      made of eosinophilic polynuclear cells surrounding rare, large and irregular, non
      septate hyphae. A filamentous fungus was isolated by cultivation of the clinical
      samples, which was identified as Conidiobolus coronatus. The patient was treated
      orally with daily doses of ketoconazole (400 mg per day). After 4 months of
      treatment, a marked regression of the facial lesion was obtained. A first
      constructive facial surgery was achieved, but the patient did not attend the
      second step. This case report allows us to remind the mycological diagnosis of
      this exotic mycosis, but also to emphasize the main difficulties encountered in
      medical management in the developing countries.

PMID- 24440612
TI  - Impact of indocyanine green fluorescent image-guided surgery for parapharyngeal
      space tumours.
AB  - In parapharyngeal space dissection, significant complications such as dysphagia
      and carotid artery rupture have been reported. In order to resect tumours safely
      in narrow parapharyngeal space, we propose indocyanine green (ICG) florescence
      image for navigation surgery. OBJECTIVE: To evaluate the usefulness of ICG
      fluorescent image-guided surgery for parapharyngeal space tumours. METHODS: 0.5
      mg/kg of ICG was injected via the cephalic vein. Observation of the fluorescent
      image was performed with HEMS (HyperEye Medical System) at 10-30 min after
      injection. At first, the position of the tumour was marked over pharyngeal mucosa
      according to ICG fluorescence imaging with HEMS. We also confirmed submucosal
      tumours hidden under fascia using HEMS imaging again and resected them. RESULTS:
      All tumours displayed bright fluorescence emissions which clearly contrasted with
      the normal structures. Even with the submucosal tumour covered with and obscured
      by fasciae, we could observe the tumour clearly under HEMS imaging. Tumours
      behind the carotid artery and lower cranial nerves also were displayed bright
      fluorescence emissions and were clearly detected. As a result, we could
      completely remove the tumour safely and noninvasively to preserve pharyngeal
      functions. CONCLUSION: ICG fluorescence imaging is effective for the detection
      and resection of the parapharyngeal space tumours with preserving functions.

PMID- 24440613
TI  - Evaluation of arthrocentesis with hyaluronic acid injection plus oral glucosamine
      hydrochloride for temporomandibular joint osteoarthritis in oral-health-related
      quality of life.
AB  - OBJECTIVES: To evaluate the changes in oral-health-related quality of life
      (OHRQoL) in patients with temporomandibular joint osteoarthritis (TMJ-OA) who
      underwent five weekly hyaluronic acid injections together with oral glucosamine
      hydrochloride for three months. MATERIALS AND METHODS: This prospective
      observational study included 211 consecutive patients who completed the Chinese
      version of the 14-item Oral Health Impact Profile (OHIP-C14) before treatment
      (T0), and at first month (T1), third month (T2), and sixth month (T3) after the
      first injection. RESULTS: Significant changes in the summary scores on OHIP-C14
      were observed during follow-up (P < 0.001). The scores were significantly reduced
      at T1, T2, and T3 compared with T0 (P < 0.001), and were significantly reduced
      from T0 to T1 (P < 0.001) and T1 to T2 (P < 0.001), but not from T2 to T3 (P =
      0.369). Compared with the norms, the scores were significantly higher at T0 (P <
      0.001), not significantly different at T1 (P = 0.482), and significantly lower at
      T2 (P = 0.013) and T3 (P = 0.003). The changes in the scores differed
      significantly among age groups (P = 0.012) but not between sexes (P = 0.293).
      CONCLUSIONS: TMJ-OA has a negative effect on patient OHRQoL. OHRQoL scores were
      improved to normal levels in both the short and long terms after therapy. OHRQoL
      improvement was the greatest in the youngest group, but did not differ between
      the sexes.

PMID- 24440615
TI  - Antibiotic prescription for sore throat or the legacy of Mr X2.

PMID- 24440614
TI  - Commensal and probiotic bacteria may prevent NEC by maturing intestinal host
      defenses.
AB  - Necrotizing enterocolitis (NEC) is a devastating disease of prematurity with
      significant morbidity and mortality. Immaturity of intestinal host defenses
      predisposes the premature infant gut to injury. An abnormal bacterial
      colonization pattern with a deficiency of commensal bacteria may lead to a
      further breakdown of these host defense mechanisms, predisposing the infant to
      NEC. The presence of probiotic and commensal bacteria within the gut has been
      shown to mature the intestinal defense system through a variety of mechanisms. We
      have shown that commensal and probiotic bacteria can promote intestinal host
      defenses by reducing apoptotic signaling, blocking inflammatory signaling, and
      maturing barrier function in immature intestinal epithelia. Future studies aimed
      at elucidating the mechanisms by which probiotic and commensal bacteria exert
      their effects will be critical to developing effective preventive therapies for
      NEC. 

PMID- 24440616
TI  - Antibiotic prescription strategies for acute sore throat: a prospective
      observational cohort study.
AB  - BACKGROUND: Data from trials suggest that antibiotics reduce the risk of
      complications of sore throat by at least 50%, but few trials for complications
      have been done in modern settings, and datasets of delayed antibiotic
      prescription are underpowered. Observational evidence is important in view of
      poor compliance with antibiotic treatment outside trials, but no prospective
      observational cohort studies have been done to date. METHODS: We generated a
      large prospective cohort from the DESCARTE study, and the PRISM component of
      DESCARTE, of 12,829 adults presenting with sore throat (<= 2 weeks duration) in
      primary care. Our follow-up of the cohort was based on a detailed and structured
      review of routine medical records, and analysis of the comparison of three
      antibiotic prescription strategies (no antibiotic prescription, immediate
      antibiotic prescription, and delayed antibiotic prescription) to control for the
      propensity to prescribe antibiotics. Information about antibiotic prescription
      was recorded in 12,677 individuals (4805 prescribed no antibiotics, 6088
      prescribed antibiotics immediately, and 1784 prescribed delayed antibiotics). We
      documented by review of patients' notes (n=11,950) the development of suppurative
      complications (eg, quinsy, impetigo and cellulitis, otitis media, and sinusitis)
      or reconsultation with new or non-resolving symptoms). We used multivariate
      analysis to control for variables significantly related to the propensity to
      prescribe antibiotics and for clustering by general practitioner. FINDINGS: 164
      (1.4%) of the 11,950 patients with information available developed complications;
      otitis media and sinusitis were the most common complications (101 patients
      [62%]). Compared with no antibiotic prescription, immediate antibiotic
      prescription was associated with fewer complications (adjusted risk ratio [RR]
      0.62, 95% CI 0.43-0.91, estimated number needed to treat [NNT 193) as was delayed
      prescription of antibiotics (0.58, 0.34-0.98; NNT 174). 1787 of the 11,950
      patients (15%) reconsulted with new or non-resolving symptoms; the risk of
      reconsultation was also reduced by immediate (0.83, 0.73-0.94; NNT 40) or delayed
      antibiotics (0.61, 0.50-0.74; NNT 18). INTERPRETATION: Suppurative complications
      are not common in primary care and most are not serious. The risks of suppurative
      complications or reconsultation in adults are reduced by antibiotics, but not as
      much as the trial evidence suggests. In most cases, no antibiotic is needed, but
      a delayed prescription strategy is likely to provide similar benefits to an
      immediate antibiotic prescription.

PMID- 24440618
TI  - Flavin-containing monooxygenase, a new clue of pathological proteins in the
      rotenone model of parkinsonism.
AB  - Parkinson's disease (PD) is a major age-related neurodegenerative disorder
      characterized by loss of dopaminergic neurons in the substantia nigra par
      compacta (SNpc) and accumulation of aggregated alpha-synuclein in brain areas.
      Rotenone is a neurotoxin that is routinely used to model PD, thus to help us
      understand the mechanisms of neural death. Flavin-containing monooxygenase (FMO),
      usually known as an important hepatic microsomal enzyme like cytochrome P450, was
      found to play a role in the brain recent years. In our study we aimed to find out
      the role that FMO might play in PD pathology. Thus we successfully generated
      rotenone model in primary midbrain dopaminergic neurons and identified the
      apoptosis of neurons caused by rotenone. We found that in rotenone model of
      Parkinsonism, the expression/protein level of parkin and FMO1 were decreased
      accompanied by the activation of caspase 3. Blocking FMO activity by FMO
      inhibitor methimazole directly caused activation of caspase 3, meanwhile parkin
      protein level was decreased. Our data indicated that FMO, whose dysfunction could
      be a reason for the apoptosis of dopaminergic neurons in rotenone model, might be
      a new clue of pathological proteins in rotenone model of parkinsonism. Meanwhile,
      it was suggested that parkin function was compromised in neuro-pathological
      states, thereby further adding to the cellular survival stress. 

PMID- 24440617
TI  - Altered expression of glial and synaptic markers in the anterior hippocampus of
      behaviorally depressed female monkeys.
AB  - The anterior hippocampus is associated with emotional functioning and hippocampal
      volume is reduced in depression. We reported reduced neuropil volume and number
      of glia in the dentate gyrus (DG) and cornu ammonis (CA)1 of the anterior
      hippocampus in behaviorally depressed adult female cynomolgus macaques. To
      determine the biochemical correlates of morphometric and behavioral differences
      between behaviorally depressed and nondepressed adult female monkeys, glial and
      synaptic transcripts and protein levels were assessed in the DG, CA3 and CA1 of
      the anterior hippocampus. Glial fibrillary acidic protein (GFAP) was increased
      whereas spinophilin and postsynaptic density (PSD)-95 protein were decreased in
      the CA1 of depressed monkeys. GFAP was reciprocally related to spinophilin and
      PSD-95 protein in the CA1. Gene expression of GFAP paralleled the protein changes
      observed in the CA1 and was inversely related to serum estradiol levels in
      depressed monkeys. These results suggest that behavioral depression in female
      primates is accompanied by astrocytic and synaptic protein alterations in the
      CA1. Moreover, these findings indicate a potential role for estrogen in
      modulating astrocyte-mediated impairments in synaptic plasticity. 

PMID- 24440619
TI  - Case report: an electrocardiogram of spontaneous pneumothorax mimicking arm lead
      reversal.
AB  - BACKGROUND: There are several previously documented findings for
      electrocardiograms (ECGs) of spontaneous pneumothorax. These findings include
      axis deviation, T-wave inversion, and right bundle branch block. When an ECG has
      the arm leads incorrectly placed, the ECG will display right axis deviation and
      inversion of the P waves in lead I. There have been no previously published ECGs
      of spontaneous pneumothorax that have shown the same findings as reversal of the
      limb leads of an ECG. OBJECTIVES: A possible finding of spontaneous pneumothorax
      is an identical finding to that of an ECG that has been flagged for limb lead
      reversal. CASE REPORT: A patient presented in the emergency setting with acute
      chest pain and shortness of breath caused by a tension pneumothorax. An ECG was
      administered; findings indicated reversal of the arm leads (right axis deviation
      and inverted P waves in lead I), but there was no actual limb lead reversal
      present. ECG findings resolved upon resolution of the pneumothorax. CONCLUSIONS:
      If a patient presents with chest pain and shortness of breath, and the patient's
      ECG is flagged for limb lead reversal despite being set up correctly, the
      physician should raise clinical suspicion for a possible spontaneous
      pneumothorax.

PMID- 24440620
TI  - Scurvy: malnourishment in the land of plenty.

PMID- 24440621
TI  - Emergency department evaluation of conducted energy weapon (CEW)-injured
      patients.

PMID- 24440622
TI  - Knowledge of alcohol impairment in boaters in southern Illinois.
AB  - BACKGROUND: Alcohol is the leading contributor to boating deaths. Earlier
      literature estimates that 30-40% of people drink alcohol while boating.
      OBJECTIVE: The objective of this study was to directly approach boaters at the
      dock to assess the prevalence of alcohol consumption while boating, as well as
      their knowledge of alcohol impairment. METHODS: This was a cross-sectional survey
      of a convenience sample of boaters aged 21 years and older at Illinois lakes and
      rivers during July 2011. Participants completed a survey of alcohol use and
      impaired boating knowledge consisting of six multiple-choice questions. A chi(2)
      analysis was used to assess knowledge differences by demographic variables.
      RESULTS: Two hundred and ten people participated. Less than one fourth of
      participants correctly answered 4 of the 5 knowledge questions. Eighty-four
      percent correctly reported the watercraft blood alcohol legal limit. Eighty-one
      percent erroneously believed that it was more dangerous for the driver to be
      intoxicated than the passenger. There were no differences in knowledge by sex,
      education, boat ownership, or driver status. Seventy-six percent admitted to
      drinking alcohol while boating. Younger participants (aged 21 to 40 years) were
      significantly more likely to report drinking while boating compared with older
      participants (p < 0.05). CONCLUSIONS: A majority of participants imbibe while
      boating and with only a rudimentary understanding of the dangers. Designated
      drivers (for boating) campaigns might falsely imply imbibing-passenger safety.
      Public health officials should readdress the dangers of passenger drinking,
      especially with the younger age group, to help decrease alcohol-related morbidity
      and mortality.

PMID- 24440623
TI  - Aortic intramural hematoma: a less common and often forgotten cause of acute
      aortic disease.

PMID- 24440624
TI  - Asymptomatic Chronic Epidural Hematoma in a Child As a Result of Extracranial
      Decompression.
AB  - BACKGROUND: Epidural hematoma (EDH) in children is a diagnostic challenge due to
      its nonspecific clinical presentation. Asymptomatic chronic epidural hematoma is
      a very rare entity. Reports of spontaneous decompression into the subgaleal
      spaces are limited with acute epidural hematomas in the literature. OBJECTIVE: We
      report a child presenting with chronic epidural hematoma at 15 days after a head
      trauma. She remained asymptomatic, owing to spontaneous decompression via a skull
      fracture. We intend to remind emergency physicians to be alert about epidural
      hematomas in asymptomatic children in the presence of a history of, even minor
      and distant, trauma. CASE PRESENTATION: An 8-year-old girl presented to the
      Emergency Department with a swelling in the right parietal region. She had fallen
      at the playground and struck her head on the ground 15 days prior. Computed
      tomography showed a mixed-density subacute-chronic parietal epidural hematoma
      with a linear fracture overlying it. There was no evidence of midline shift or
      ipsilateral ventricular compression. CONCLUSION: An initially minimal but
      expanding EDH in a child can remain asymptomatic even in the later phases, owing
      to the spontaneous decompression through a skull fracture.

PMID- 24440626
TI  - Febrile illness in a traveler.

PMID- 24440627
TI  - Atrial flutter with 1:1 conduction in undiagnosed Wolff-Parkinson-White syndrome.
AB  - BACKGROUND: Atrial flutter with 1:1 atrioventricular conduction via an accessory
      pathway is an uncommon presentation of Wolff-Parkinson-White syndrome not
      previously reported in the emergency medicine literature. Wolff-Parkinson-White
      syndrome, a form of ventricular preexcitation sometimes initially seen and
      diagnosed in the emergency department (ED), can present with varied
      tachydysrhythmias for which certain treatments are contraindicated. For instance,
      atrial fibrillation with preexcited conduction needs specific consideration of
      medication choice to avoid potential degeneration into ventricular fibrillation.
      CASE REPORT: We describe an adult female presenting with a very rapid, regular
      wide complex tachycardia successfully cardioverted in the ED followed by a normal
      electrocardiogram (ECG). Electrophysiology study confirmed atrial flutter with
      1:1 conduction and revealed an accessory pathway consistent with Wolff-Parkinson
      White syndrome, despite lack of ECG findings of preexcitation during sinus
      rhythm. Why should an emergency physician be aware of this? Ventricular
      tachycardia must be the first consideration in patients with regular wide complex
      tachycardia. However, clinicians should consider atrial flutter with 1:1
      conduction related to an accessory pathway when treating patients with the triad
      of very rapid rate (>250 beats/min), wide QRS complex, and regular rhythm,
      especially when considering pharmacologic treatment. Emergency physicians also
      should be aware of electrocardiographically concealed accessory pathways, and
      that lack of delta waves does not rule out preexcitation syndromes such as Wolff
      Parkinson-White syndrome.

PMID- 24440628
TI  - Erythropoietin prevents cognitive impairment and oxidative parameters in Wistar
      rats subjected to pneumococcal meningitis.
AB  - Pneumococcal meningitis is characterized by a severe inflammatory reaction in the
      subarachnoid and ventricular space of the brain, disruption of the blood-brain
      barrier, hearing loss, and neurologic sequelae in as many as 27% of surviving
      patients. Several experimental studies have shown that erythropoietin (EPO) and
      its receptor are expressed in the central nervous system and have neuroprotective
      properties through the inhibition of apoptosis, as well as anti-inflammatory,
      antioxidant, angiogenic, and neurotrophic effects. In the current study, we
      demonstrated the effect of erythropoietin (EPO) on lipid peroxidation, protein
      carbonylation, superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO),
      and behavioral parameters in rats with pneumococcal meningitis. EPO decreased
      lipid peroxidation and protein carbonylation, and it prevented protein
      degradation in the hippocampus and frontal cortex. MPO activity was decreased,
      and both SOD and CAT activity were increased in the first 6 hours after
      pneumococcal meningitis induction. Novel object recognition memory was impaired
      in the meningitis group; however, adjuvant treatment with EPO prevented memory
      impairment during both the short- and long-term retention tests. The meningitis
      group showed no difference in motor and exploratory activity between training and
      test sessions in the open-field task, which indicates that habituation memory was
      impaired; however, adjuvant treatment with EPO prevented habituation memory
      impairment. Although there are some limitations with respect to the animal model
      of pneumococcal meningitis, this study suggests that adjuvant treatment with EPO
      contributed to decreased oxidative stress and prevented cognitive impairment. 

PMID- 24440630
TI  - Unique nuclear vacuoles in the motor neurons of conditional ADAR2-knockout mice.
AB  - A reduction in adenosine deaminase acting on RNA 2 (ADAR2) activity causes the
      death of spinal motor neurons specifically via the GluA2 Q/R site-RNA editing
      failure in sporadic amyotrophic lateral sclerosis (ALS). We studied, over time,
      the spinal cords of ADAR2-knockout mice, which are the mechanistic model mice for
      sporadic ALS, using homozygous ADAR2(flox/flox)/VAChT-Cre.Fast (AR2), homozygous
      ADAR2(flox/flox)/VAChT-Cre.Slow (AR2Slow), and heterozygous ADAR2(flox/+)/VAChT
      Cre.Fast (AR2H) mice. The conditional ADAR2-knockout mice were divided into 3
      groups by stage: presymptomatic (AR2H mice), early symptomatic (AR2 mice, AR2H
      mice) and late symptomatic (AR2Slow mice). Light-microscopically, some motor
      neurons in AR2 and AR2H mice (presymptomatic) showed simple neuronal atrophy and
      astrogliosis, and AR2H (early symptomatic) and AR2Slow mice often showed vacuoles
      predominantly in motor neurons. The number of vacuole-bearing anterior horn
      neurons decreased with the loss of anterior horn neurons in AR2H mice after 40
      weeks of age. Electron-microscopically, in AR2 mice, while the cytoplasm of
      normal-looking motor neurons was almost always normal-appearing, the interior of
      dendrites was frequently loose and disorganized. In AR2H and AR2Slow mice, large
      vacuoles without a limiting membrane were observed in the anterior horns,
      preferentially in the nuclei of motor neurons, astrocytes and oligodendrocytes.
      Nuclear vacuoles were not observed in AR2res (ADAR2(flox/flox)/VAChT
      Cre.Fast/GluR-B(R/R)) mice, in which motor neurons express edited GluA2 in the
      absence of ADAR2. These findings suggest that ADAR2-reduction is associated with
      progressive deterioration of nuclear architecture, resulting in vacuolated nuclei
      due to a Ca(2+)-permeable AMPA receptor-mediated mechanism. 

PMID- 24440629
TI  - Effects of perinatal bisphenol A exposure during early development on radial arm
      maze behavior in adult male and female rats.
AB  - Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety
      behavior. However, no studies have examined whether administration of this
      endocrine disruptor during the perinatal period has the potential to induce
      alterations in cognitive behavior in both adult males and females as assessed in
      an appetitive task. The goal of the current study was to determine whether
      exposure to different doses of BPA during early development alters performance on
      the 17-arm radial maze in adulthood in Long-Evans rats. Oral administration of
      corn oil (vehicle), 4 MUg/kg, 40 MUg/kg, or 400 MUg/kg BPA to the dams occurred
      daily throughout pregnancy, and the pups received direct oral administration of
      BPA between postnatal days 1-9. Blood was collected from offspring at weaning age
      to determine levels of several hormones (thyroxine, thyroid stimulating hormone,
      follicle stimulating hormone, luteinizing hormone). One male and one female from
      each litter were evaluated on the 17-arm radial maze, a working/reference memory
      task, in adulthood. Results indicated that after exposure to BPA at both 4 and
      400 MUg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There
      were no significant effects of BPA on performance on the radial arm maze in males
      or females. In conclusion, exposure to BPA during early development had modest
      effects on circulating hormones but did not affect performance on a spatial
      learning and memory task.

PMID- 24440631
TI  - Real-time hemodynamic response and mitochondrial function changes with
      intracarotid mannitol injection.
AB  - Disruption of blood brain barrier (BBB) is used to enhance chemotherapeutic drug
      delivery. The purpose of this study was to understand the time course of
      hemodynamic and metabolic response to intraarterial (IA) mannitol infusions in
      order to optimize the delivery of drugs for treating brain tumors. PRINCIPAL
      RESULTS: We compared hemodynamic response, EEG changes, and mitochondrial
      function as judged by relative changes in tissue NADH concentrations, after
      intracarotid (IC) infusion of equal volumes of normal saline and mannitol in our
      rabbit IC drug delivery model. We observed significantly greater, though
      transient, hyperemic response to IC infusion of mannitol compared to normal
      saline. Infusion of mannitol also resulted in a greater increase in tissue NADH
      concentrations relative to the baseline. These hemodynamic, and metabolic changes
      returned to baseline within 5min of mannitol injection. CONCLUSION: Significant,
      though transient, changes in blood flow and brain metabolism occur with IA
      mannitol infusion. The observed transient hyperemia would suggest that
      intravenous (IV) chemotherapy should be administered either just before, or
      concurrent with IA mannitol injections. On the other hand, IA chemotherapy should
      be delayed until the peak hyperemic response has subsided.

PMID- 24440632
TI  - The coupling features of electrical synapses modulate neuronal synchrony in
      hypothalamic superachiasmatic nucleus.
AB  - Electrical synapses (gap junctions) exist in many types of neurons in the
      mammalian brain, especially during early development period; one of the most
      important roles of electrical synapses is to mediate the synchrony of the
      neuronal networks and to coordinate the neural circuits function precisely.
      Previous reports show that electrical coupling is involved in modulating
      synchronous activity among coupled neurons, but related dynamics and mechanisms
      are still poorly understood. Here, in order to investigate the correlation
      between gap junctions and synchrony we focus on the electrically coupled neurons
      in suprachiasmatic nucleus (SCN) by using calcium imaging with two-photon
      microscopy and electrophysiology. We observed that coupled neurons in SCN present
      a dynamic regulation on synchrony based on their coupling strengths and are
      modulated by vasoactive intestinal peptide (VIP) - a neuropeptide whose receptors
      are expressed throughout the SCN. Modification of coupling efficiency of
      electrical synapses changes the synchrony level of the neuronal networks in the
      SCN. Our results provide new insights into the causal relationship between gap
      junctions and synchrony in the SCN. We further demonstrate the importance of VIP
      in coordinating the gap junctions-mediated signal transmission and implicate that
      a homeostasis environment is important for SCN to modulate the rhythmic circadian
      activities. 

PMID- 24440633
TI  - Impact of an N-terminal extension on the stability and activity of the GH11
      xylanase from Thermobacillus xylanilyticus.
AB  - To understand structure-function relationships in the N-terminal region of GH11
      xylanases, the 17 N-terminal amino acids of the GH11 xylanase from Neocallimastix
      patriciarum (Np-Xyn) have been grafted onto the N-terminal extremity of the
      untypically short GH11 xylanase from Thermobacillus xylanilyticus (Tx-Xyn),
      creating a hybrid enzyme denoted NTfus. The hybrid xylanase displayed properties
      (pH and temperature optima) similar to those of the parental enzyme, although
      thermostability was lowered, with the Tm value, being reduced by 5 degrees C.
      Kinetic assays using oNP-Xylo-oligosaccharides (DP2 and 3) indicated that the N
      extension did not procure more extensive substrate binding, even when further
      mutagenesis was performed to promote this. However, these experiments confirmed
      weak subsite -3 for both NTfus and the parental enzyme. The catalytic efficiency
      of NTfus was shown to be 17% higher than that of the parental enzyme on low
      viscosity wheat arabinoxylan and trials using milled wheat straw as the substrate
      revealed that NTfus released more substituted oligosaccharide products
      (Xyl/Ara=8.97+/-0.13 compared to Xyl/Ara=9.70+/-0.21 for the parental enzyme),
      suggesting that the hybrid enzyme possesses wider substrate selectivity.
      Combining either the parental enzyme or NTfus with the cellulolytic cocktail
      Accellerase 1500 boosted the impact of the latter on wheat straw, procuring
      yields of solubilized xylose and glucose of 23 and 24% of theoretical yield,
      respectively, thus underlining the benefits of added xylanase activity when using
      this cellulase cocktail. Overall, in view of the results obtained for NTfus, we
      propose that the N-terminal extension leads to the modification of a putative
      secondary substrate binding site, a hypothesis that is highly consistent with
      previous data. 

PMID- 24440634
TI  - Probing the role of helix alpha1 in the acid-tolerance and thermal stability of
      the Streptomyces sp. SK Glucose Isomerase by site-directed mutagenesis.
AB  - In order to investigate the role of helix alpha1 in the different biochemical
      properties between class I and class II Glucose Isomerases, a histidine and a
      phenylalanine residue were inserted at position 17 and 19 of Streptomyces sp. SK
      Glucose Isomerase (SKGI). In addition, W16 was substituted by a histidine. The
      H17/F19 insertion displaced the optimal pH of SKGI from 6.5 to 7-8 and slightly
      decreased the thermostability. As for the W16H mutant, a shift in optimal pH of
      SKGI from 6.5 to 6 was observed along with a decrease in the enzyme
      thermostability at 85 degrees C with a half-life time reduced twice compared to
      the wild-type enzyme. Three-dimensional structure analysis suggested that the
      insertion of a histidine at position 17 results in the formation of new hydrogen
      bond with D287, thereby preventing it from deprotonating the O2 hydroxyl of the
      sugar at low pH, while the substitution W16H induced opposite effect by
      preventing hydrogen bond formation between D287 and W16 and thereby probably
      facilitating the hydrogen transfer during the isomerization reaction. The
      findings highlight the essential role of helix alpha1, which bears the three
      introduced mutations, in the acid-tolerance and the thermostability of SKGI and
      of glucose isomerases in general. 

PMID- 24440635
TI  - A process for producing lignocellulosic flocs from NSSC spent liquor.
AB  - Presently, the spent liquor (SL) of neutral sulfite semi chemical (NSSC) pulping
      process is treated in the waste water system. In this work, a new process for
      isolating lignocelluloses from the SL of an NSSC process is proposed and the
      effectiveness of this process is evaluated on industrially produced SL. The
      results showed that under the optimal conditions of pH 6, 30 degrees C and 15mg/g
      poly ethylene imine (PEI) concentration in the SL, a maximum of 37% lignin and
      37% hemicelluloses could be removed from SL. Alternatively, the dual system of
      poly diallyldimethyl ammonium chloride (PDADMAC) and PEI (7.5mg/g each) was
      evaluated in removing lignocelluloses from the SL; and the results showed that
      lignin and hemicellulose removals were improved to 47% and 50%, respectively. The
      turbidity and chemical oxygen demand (COD) of SL, as well as the elemental
      analysis of generated flocs were also assessed in this work. 

PMID- 24440636
TI  - Mammalian Fe-S cluster biogenesis and its implication in disease.
AB  - Iron-sulfur (Fe-S) clusters are inorganic cofactors that are ubiquitous and
      essential. Due to their chemical versatility, Fe-S clusters are implicated in a
      wide range of protein functions including mitochondrial respiration and DNA
      repair. Composed of iron and sulfur, they are sensible to oxygen and their
      biogenesis requires a highly conserved protein machinery that facilitates
      assembly of the cluster as well as its insertion into apoproteins. Mitochondria
      are the central cellular compartment for Fe-S cluster biogenesis in eukaryotic
      cells and the importance of proper function of this biogenesis for life is
      highlighted by a constantly increasing number of human genetic diseases that are
      associated with dysfunction of this Fe-S cluster biogenesis pathway. Although
      these disorders are rare and appear dissimilar, common aspects are found among
      them. This review will give an overview on what is known on mammalian Fe-S
      cluster biogenesis today, by putting it into the context of what is known from
      studies from lower model organisms, and focuses on the associated diseases, by
      drawing attention to the respective mutations. Finally, it outlines the
      importance of adequate cellular and murine models to uncover not only each
      protein function, but to resolve their role and requirement throughout the
      mammalian organism. 

PMID- 24440638
TI  - Enzymatic enantioselective aldol reactions of isatin derivatives with cyclic
      ketones under solvent-free conditions.
AB  - Nuclease p1 from Penicillium citrinum was observed to directly catalyze the
      asymmetric aldol reactions between isatin derivatives and cyclic ketones with
      high isolated yields (up to 95%) and moderate to good stereoselectivity (dr up to
      >99/1, ee up to 82%). A series of reaction conditions were investigated in
      detail, and the addition of deionized water had a big influence upon the enzyme
      activity. This case of biocatalytic promiscuity not only widens the applicability
      of nuclease p1 to new chemical transformation in organic synthesis, but also
      provides a potentially valuable method to construct pharmaceutically active
      compounds in medicinal chemistry.

PMID- 24440637
TI  - Mitochondrial RNA editing in trypanosomes: small RNAs in control.
AB  - Mitochondrial mRNA editing in trypanosomes is a posttranscriptional processing
      pathway thereby uridine residues (Us) are inserted into, or deleted from,
      messenger RNA precursors. By correcting frameshifts, introducing start and stop
      codons, and often adding most of the coding sequence, editing restores open
      reading frames for mitochondrially-encoded mRNAs. There can be hundreds of
      editing events in a single pre-mRNA, typically spaced by few nucleotides, with U
      insertions outnumbering U-deletions by approximately 10-fold. The mitochondrial
      genome is composed of ~50 maxicircles and thousands of minicircles. Catenated
      maxi- and minicircles are packed into a dense structure called the kinetoplast;
      maxicircles yield rRNA and mRNA precursors while guide RNAs (gRNAs) are produced
      predominantly from minicircles, although varying numbers of maxicircle-encoded
      gRNAs have been identified in kinetoplastids species. Guide RNAs specify
      positions and the numbers of inserted or deleted Us by hybridizing to pre-mRNA
      and forming series of mismatches. These 50-60 nucleotide (nt) molecules are 3'
      uridylated by RET1 TUTase and stabilized via association with the gRNA binding
      complex (GRBC). Editing reactions of mRNA cleavage, U-insertion or deletion, and
      ligation are catalyzed by the RNA editing core complex (RECC). To function in
      mitochondrial translation, pre-mRNAs must further undergo post-editing 3'
      modification by polyadenylation/uridylation. Recent studies revealed a highly
      compound nature of mRNA editing and polyadenylation complexes and their
      interactions with the translational machinery. Here we focus on mechanisms of RNA
      editing and its functional coupling with pre- and post-editing 3' mRNA
      modification and gRNA maturation pathways. 

PMID- 24440639
TI  - A re-assessment of treatment with a tyrosine kinase inhibitor (imatinib) on
      tissue sparing and functional recovery after spinal cord injury.
AB  - This study was undertaken as part of the NIH "Facilities of Research Excellence
      Spinal Cord Injury" project to support independent replication of published
      studies. Here, we repeat key parts of a study reporting that rats treated with
      imatinib (Gleevec(r), Novartis) after spinal cord contusion injury exhibited
      enhanced bladder function, greater recovery of motor function, and increased
      tissue sparing. Young adult female SCA Sprague-Dawley rats received moderate
      contusion injuries at T9-T10 using the MASCIS weight drop device. One group
      (n=16) received oral doses of imatinib 30min after injury and then daily doses
      for 5days. A control group (n=18) received vehicle. Motor function was assessed
      with the BBB locomotor rating scale and a contact plantar placement task. Bladder
      function was assessed by measuring the amount of urine retained in the bladder.
      Tissue preservation was assessed by immunostaining and stereological analysis.
      Rats that received imatinib had lower volumes of retained urine, suggesting
      improved bladder function, but there were no significant differences in motor
      function on any of the other tasks. Tissue preservation was assessed by
      immunostaining and stereological analysis. Quantitative analysis of spared
      tissue, cyst size, spared white matter, and inflammatory cell invasion revealed
      no significant differences between imatinib treated and control rats. Taken
      together our results confirm the findings that treatment with imatinib improves
      bladder function after SCI but fail to replicate findings of improved motor
      function, enhanced tissue sparing, and decreased inflammatory cell invasion. 

PMID- 24440640
TI  - Neonatal immune-tolerance in mice does not prevent xenograft rejection.
AB  - Assessing the efficacy of human stem cell transplantation in rodent models is
      complicated by the significant immune rejection that occurs. Two recent reports
      have shown conflicting results using neonatal tolerance to xenografts in rats.
      Here we extend this approach to mice and assess whether neonatal tolerance can
      prevent the rapid rejection of xenografts. In three strains of neonatal immune
      intact mice, using two different brain transplant regimes and three independent
      stem cell types, we conclusively show that there is rapid rejection of the
      implanted cells. We also address specific challenges associated with the
      generation of humanized mouse models of disease. 

PMID- 24440641
TI  - Sex steroids and neuroprotection in spinal cord injury: a review of preclinical
      investigations.
AB  - Spinal cord injury (SCI) is a debilitating condition that affects motor, sensory
      and autonomic functions. Subsequent to the first mechanical trauma, secondary
      events, which include inflammation and glial activation, exacerbate tissue damage
      and worsen functional deficits. Although these secondary injury mechanisms are
      amenable to therapeutic interventions, the efficacy of current approaches is
      inadequate. Further investigations are necessary to implement new therapies that
      can protect neural cells and attenuate some of the detrimental effects of
      inflammation while promoting regeneration. Studies on different animal models of
      SCI indicated that sex steroids, especially 17beta-estradiol and progesterone,
      exert neuroprotective, anti-apoptotic and anti-inflammatory effects, ameliorate
      tissue sparing and improve functional deficits in SCI. As sex steroid receptors
      are expressed in a variety of cells including neurons, glia and immune system
      related cells which infiltrate the injury epicenter, sex steroids could impact
      multiple processes simultaneously and in doing so, influence the outcomes of SCI.
      However, the translation of these pre-clinical findings into the clinical setting
      presents challenges such as the narrow therapeutic time window of sex steroid
      administration, the diversity of treatment regimens that have been employed in
      animal studies and the lack of sufficient information regarding the persistence
      of the effects in chronic SCI. The current review will summarize some of the
      major findings in this field and will discuss the challenges associated with the
      implementation of sex steroids as a promising treatment in human SCI. 

PMID- 24440643
TI  - Effect of Tai Chi on physical function, fall rates and quality of life among
      older stroke survivors.
AB  - OBJECTIVE: To examine the effect of a 12-week Tai Chi (TC) intervention on
      physical function and quality of life. DESIGN: Single-blind, randomized
      controlled trial. SETTING: General community. PARTICIPANTS: Community-dwelling
      survivors of stroke (N=145; 47% women; mean age, 70y; time poststroke: 3y;
      ischemic stroke: 66%; hemiparesis: 73%) who were aged >=50 years and were >=3
      months poststroke. INTERVENTIONS: Yang style 24-posture short-form TC (n=53),
      strength and range of movement exercises (SS) (n=44), or usual care (UC) (n=48)
      for 12 weeks. The TC and SS groups attended a 1-hour class 3 times per week,
      whereas the UC group had weekly phone calls. MAIN OUTCOME MEASURES: Physical
      function: Short Physical Performance Battery, fall rates, and 2-minute step test;
      quality of life: Medical Outcomes Study 36-Item Short-Form Health Survey, Center
      for Epidemiologic Studies Depression Scale, and Pittsburgh Sleep Quality Index.
      RESULTS: During the intervention, TC participants had two thirds fewer falls (5
      falls) than the SS (14 falls) and UC (15 falls) groups (chi(2)=5.6, P=.06). There
      was a significant group by time interaction for the 2-minute step test
      (F2,142=4.69, P<.01). Post hoc tests indicated that the TC (t53=2.45, P=.02) and
      SS (t44=4.63, P<.01) groups had significantly better aerobic endurance over time,
      though not in the UC group (t48=1.58, P=.12). Intervention adherence rates were
      85%. CONCLUSIONS: TC and SS led to improved aerobic endurance, and both are
      suitable community-based programs that may aid in stroke recovery and community
      reintegration. Our data suggest that a 12-week TC intervention was more effective
      in reducing fall rates than SS or UC interventions. Future studies examining the
      effectiveness of TC as a fall prevention strategy for community-dwelling
      survivors of stroke are recommended.

PMID- 24440642
TI  - Astroglial heme oxygenase-1 and the origin of corpora amylacea in aging and
      degenerating neural tissues.
AB  - BACKGROUND: Corpora amylacea (CA) are glycoproteinaceous (predominantly glial and
      extracellular) inclusions that accumulate in normal aging brain and, to a greater
      extent, in Alzheimer disease (AD). Previous pharmacological evidence suggested
      that up-regulation of endogenous heme oxygenase-1 (HO-1) in astrocytes promotes
      transformation of normal mitochondria to CA-like inclusions. Here, we determined
      whether 1) HMOX1 transfection fosters the accumulation of CA-like inclusions in
      cultured rat astroglia; 2) the HMOX1 transgene promotes CA formation in the
      brains of aging GFAP.HMOX1 mice; and 3) brain mitochondrial damage and CA
      biogenesis are augmented in persons with mild cognitive impairment (MCI), a
      harbinger of AD. METHODS: CA were ascertained in (i) neonatal rat astroglia
      transfected with flag-tagged human HO-1 cDNA, (ii) brain sections derived from
      19month-old GFAP.HMOX1 and wild-type (WT) mice, and (iii) post-mortem hippocampal
      sections from individuals with mild (MCI) and no cognitive impairment (NCI) after
      staining with PAS or antisera against HO-1, ubiquitin (Ub), manganese superoxide
      dismutase (MnSOD), and alpha-synuclein or tyrosine hydroxylase (TH). RESULTS:
      HMOX1 transfection induced cytoplasmic vacuolation and the accumulation of PAS+
      inclusions in cultured astroglia. Numerous CA-like inclusions stained with PAS
      and immunoreactive for HO-1, Ub and MnSOD were observed in the brains of
      GFAP.HMOX1 mice, but were rarely encountered in age-matched, WT controls. Numbers
      of HO-1-positive CA were significantly increased in certain hippocampal strata of
      MCI subjects relative to NCI preparations. MnSOD and Ub proteins co-localized to
      CA in both the control and MCI specimens. CONCLUSIONS: HO-1 promotes
      mitochondrial damage and CA biogenesis in astrocyte cultures and in the intact
      aging brain. CA formation is enhanced in the MCI hippocampus and thus occurs
      relatively early in the pathogenesis of AD. Glial HO-1 suppression may attenuate
      bioenergetic failure and slow disease progression in AD and other
      neurodegenerative conditions featuring accelerated accumulation of CA.

PMID- 24440644
TI  - Comparisons of presentations and outcomes of cryptococcal meningitis between
      patients with and without hepatitis B virus infection.
AB  - OBJECTIVE: The clinical characteristics and outcomes in cryptococcal meningitis
      (CM) have been shown to vary depending on the underlying condition. The purpose
      of this study was to investigate these differences in patients with and without
      hepatitis B virus (HBV) infection. METHODS: We performed a retrospective study at
      the Third Affiliated Hospital of Sun Yat-Sen University from January 2006 to June
      2012. Thirty-two HBV-positive patients and 58 HBV-negative patients were
      included. RESULTS: Among the 90 patients with CM, 32 (35.6%) were HBV-infected.
      CM occurred in a younger population in the HBV-positive group, with a higher
      Charlson comorbidity score than the HBV-negative group. The HBV-positive group
      presented with lower initial complaints of visual symptoms, lower cerebrospinal
      fluid (CSF) white blood cell counts, lower percentages of the total protein in
      the CSF exceeding 0.45 g/l, higher glucose levels in the CSF, a higher percentage
      of positive results for Cryptococcus culture in the CSF, more extraneural
      involvement sites, and a higher proportion of normal brain images than the HBV
      negative group. Factors for a poor prognosis in the HBV-positive group included
      liver cirrhosis and HBV DNA >103 copies/ml. In the HBV-uninfected group, lower
      glucose in the CSF and hydrocephalus were the indicators of an unsatisfactory
      outcome. CONCLUSIONS: Certain clinical features of CM were found to be
      significantly different between HBV-infected and HBV-uninfected patients,
      including age and initial laboratory findings, as well as the indicators of an
      unsatisfactory outcome. Host defense defects in the HBV-infected group may lead
      to a lower intensity of inflammation in the pathogenesis of CM compared with the
      HBV-uninfected patients and may account for these divergences between the two
      groups.

PMID- 24440646
TI  - Altered phenotype and function of NK cells infiltrating human papillomavirus
      (HPV)-associated genital warts during HIV infection.
AB  - HIV-infected individuals experience more persistent HPV infections and are less
      likely to resolve genital warts. This study compared phenotype and functions of
      NK and T cells from genital warts and blood from 67 women. We compared in vitro
      functional responses of NK and T cells by multiparametric flow cytometry. HIV+
      women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and
      blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV+
      women tended to have lower frequencies of CD56(Dim) NK cells in both blood (p =
      0.0001) and warts (p = 0.006) than HIV- women. Wart NK cells from HIV+ women
      expressed significantly lower CD107a and produced IFN-gamma. HAART status was not
      associated with differences in NK cell functionality. We conclude that wart NK
      cells from HIV+ women have defects in their ability to degranulate and/or secrete
      IFN-gamma, which may provide insights into why HIV+ women fail to spontaneously
      resolve genital warts.

PMID- 24440645
TI  - SLAP deficiency decreases dsDNA autoantibody production.
AB  - Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to
      activated components of the BCR signaling complex regulating BCR levels and
      signaling in developing B cells. Based on this function, we asked whether SLAP
      deficiency could decrease the threshold for tolerance and eliminate development
      of autoreactive B cells in two models of autoantibody production. First, we
      sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite
      equivalent production of anti-peptide antibodies compared to BALB/c controls,
      SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance
      model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies
      compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical
      regulator of B-cell development and function and its deficiency leads to
      decreased autoreactive B cells that are otherwise maintained by inefficient
      receptor editing or failed negative selection. 

PMID- 24440647
TI  - Flow cytometry biomarkers distinguish DOCK8 deficiency from severe atopic
      dermatitis.
AB  - DOCK8 deficiency is a primary immunodeficiency characterized by recurrent
      sinopulmonary infections, dermatitis with cutaneous infections, elevated serum
      IgE levels, eosinophilia, and a high incidence of food allergy. Given the
      seriousness of DOCK8 deficiency, it is important to recognize it early and
      initiate appropriate therapy. Diagnosis relies on examining DOCK8 protein
      expression and sequencing of the 48 exons in the DOCK8 gene, but these assays are
      not always readily available. A major problem facing clinicians is that DOCK8
      deficiency shares many clinical and laboratory features with severe atopic
      dermatitis. Here, we have identified biomarkers routinely measured by flow
      cytometry on whole blood in clinical immunology laboratories that may be used in
      distinguishing DOCK8 deficiency from severe atopic dermatitis. The use of these
      biomarkers may help the clinician identify those patients who are most likely to
      have DOCK8 mutations and would benefit from further specialized diagnostic
      testing. 

PMID- 24440649
TI  - Cost of care using prophylactic negative pressure wound vacuum on closed
      laparotomy incisions.
AB  - OBJECTIVE: We wished to determine the reduction in the rate of wound
      complications that would render the use of prophylactic negative pressure wound
      vacuum therapy (NPWT) cost saving compared to routine incision care (RC)
      following laparotomy for gynecologic malignancy. METHODS: A decision tree was
      designed from a payer perspective to compare strategies for incision management
      following laparotomy for gynecologic malignancy: (1) RC; (2) prophylactic NPWT.
      Rates of wound complication, antibiotic use, re-hospitalization, re-operation,
      and home health use were obtained from a published cohort of 431 women who
      underwent laparotomy for endometrial cancer 2002-2007. Costs were estimated using
      Medicare reimbursements; cost of NPWT ($200) was obtained from hospital financial
      department. A 50% reduction in wound complications using NPWT was assigned
      initially and varied for sensitivity analysis. RESULTS: The mean BMI was 36. The
      wound complication rate was 31% (37% for BMI>30, 41% for BMI>40). The overall
      cost of incision care was $104 lower for NPWT than for RC. At the lowest cost of
      NPWT ($200), the risk of wound complication must be reduced by 33% (relative
      risk=0.67) for NPWT to achieve cost savings in this cohort. Modeling obese and
      morbidly obese cohorts, the NPWT resulted in overall cost savings of $163 and
      $203, respectively, and the risk of wound complication must be reduced by 28% and
      25%, respectively, for NPWT to achieve cost savings. CONCLUSION: If the wound
      complication rate can be reduced by one-third, prophylactic NPWT is potentially
      cost saving in high-risk women undergoing laparotomy for gynecologic malignancy.

PMID- 24440650
TI  - [Results of the Austrian CT dose study 2010: typical effective doses of the most
      frequent CT examinations].
AB  - PURPOSE: To determine typical doses from common CT examinations of standard sized
      adult patients and their variability between CT operators for common CT
      indications. MATERIALS AND METHODS: In a nationwide Austrian CT dose survey doses
      from approx. 10,000 common CT examinations of adults during 2009 and 2010 were
      collected and "typical" radiation doses to the "average patient", which turned
      out to have 75.6kg body mass, calculated. Conversion coefficients from DLP to
      effective dose were determined and effective doses calculated according to ICRP
      103. Variations of typically applied doses to the "average patient" were
      expressed as ratios between 90(th) and 10(th) percentile (inter-percentile width,
      IPW90/10), 1(st) and 3(rd) quartile (IPW75/25), and Maximum/Minimum. RESULTS:
      Median effective doses to the average patients for standard head and neck scans
      were 1.8 mSv (cervical spine), 1.9 mSv (brain: trauma/bleeding, stroke) to 2.2
      mSv (brain: masses) with typical variation between facilities of a factor 2.5
      (IPW90/10) and 1.7 (IPW75/25). In the thorax region doses were 6.4 to 6.8 mSv
      (pulmonary embolism, pneumonia and inflammation, oncologic scans), the variation
      between facilities was by a factor of 2.1 (IPW90/10) and 1.5 (IPW75/25),
      respectively. In the abdominal region median effective doses from 6.5 mSv (kidney
      stone search) to 22 mSv (liver lesions) were found (acute abdomen,
      staging/metastases, lumbar spine: 9-12 mSv; oncologic abdomen plus chest 16 mSv;
      renal tumor 20 mSv). Variation factors between facilities were on average for
      abdominal scans 2.7 (IPW90/10) and 1.8 (IPW75/25). CONCLUSION: Variations between
      CT operators are generally moderate for most operators, but in some indications
      the ratio between the minimum and the maximum of average dose to the typical
      standard patients exceeds a factor of 4 or even 5. Therefore, comparing average
      doses to Diagnostic Reference Levels (DRLs) and optimizing protocols need to be
      encouraged.

PMID- 24440648
TI  - Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic
      hematopoietic cell transplantation in patients with myelodysplastic syndrome and
      acute myeloid leukemia.
AB  - Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for
      many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia
      (AML). However, post-HCT relapse remains a major problem, particularly in
      patients with high-risk cytogenetics. In this prospective phase II trial, we
      assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total
      body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or
      AML. Ninety-six patients with MDS (n = 36: 15 refractory cytopenia with
      multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10
      refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia
      type 1) or AML (n = 60: 35 first complete remission [CR], 18 second CR, 3
      advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to
      60) years. Twelve patients had undergone a prior HCT with high-intensity
      conditioning. Patients received 14 g/m(2)/day treosulfan i.v. on days -6 to -4,
      30 mg/m(2)/day fludarabine i.v. on days -6 to -2, and 2 Gy TBI on day 0, followed
      by infusion of hematopoietic cells from related (n = 27) or unrelated (n = 69)
      donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and
      methotrexate. With a median follow-up of 30 months, the 2-year overall survival
      (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%,
      respectively. The incidences of grades II to IV (III to IV) acute and chronic
      graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was
      not significantly different between MDS patients with poor-risk and
      good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML
      patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and
      76%, respectively). In AML patients, minimal residual disease (MRD; n = 10) at
      the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS
      (41% versus 79%) at 2 years, when compared with patients without MRD. In
      conclusion, treosulfan, fludarabine, and low-dose TBI provided effective
      conditioning for allogeneic HCT in patients with MDS or AML and resulted in low
      relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at
      the time of HCT remained a risk factor for post-HCT relapse.

PMID- 24440651
TI  - Sequential chemical-biological processes for the treatment of industrial
      wastewaters: review of recent progresses and critical assessment.
AB  - When direct wastewater biological treatment is unfeasible, a cost- and resource
      efficient alternative to direct chemical treatment consists of combining
      biological treatment with a chemical pre-treatment aiming to convert the
      hazardous pollutants into more biodegradable compounds. Whereas the principles
      and advantages of sequential treatment have been demonstrated for a broad range
      of pollutants and process configurations, recent progresses (2011-present) in the
      field provide the basis for refining assessment of feasibility, costs, and
      environmental impacts. This paper thus reviews recent real wastewater
      demonstrations at pilot and full scale as well as new process configurations. It
      also discusses new insights on the potential impacts of microbial community
      dynamics on process feasibility, design and operation. Finally, it sheds light on
      a critical issue that has not yet been properly addressed in the field:
      integration requires complex and tailored optimization and, of paramount
      importance to full-scale application, is sensitive to uncertainty and variability
      in the inputs used for process design and operation. Future research is therefore
      critically needed to improve process control and better assess the real potential
      of sequential chemical-biological processes for industrial wastewater treatment. 

PMID- 24440652
TI  - Synthesis and characterization of novel macroporous silica-polymer-calixcrown
      hybrid supramolecular recognition materials for effective separation of cesium.
AB  - Two novel macroporous silica-polymer-calixcrown hybrid supramolecular recognition
      materials, 25,27-bis(n-octyloxy)calix[4]arene-crown-6 (BnOCalix[4]C6)/SiO2-P and
      25,27-bis(i-octyloxy)calix[4]arene-crown-6 (BiOCalix[4]C6)/SiO2-P were
      synthesized by in situ polymerization and impregnation techniques. The obtained
      materials were characterized by scanning electron microscope (SEM), particle size
      distribution, nitrogen adsorption-desorption isotherms, thermogravimetric
      analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, (29)Si solid
      state NMR, and powder X-ray diffraction (XRD). The adsorption of some typical
      fission and non-fission products Na(I), K(I), Rb(I), Cs(I), Sr(II), Ba(II),
      La(III), Y(III), Pd(II), Ru(III), Zr(IV), and Mo(VI) onto BnOCalix[4]C6/SiO2-P
      and BiOCalix[4]C6/SiO2-P in HNO3 solution was investigated. The bleeding of the
      materials in HNO3 solution was evaluated by analysis of total organic carbon
      (TOC). BnOCalix[4]C6/SiO2-P and BiOCalix[4]C6/SiO2-P exhibited excellent
      adsorption ability and high selectivity for Cs(I) over all the other tested
      metals. 

PMID- 24440653
TI  - Biodegradation of 3,4 dichloroaniline by fungal isolated from the preconditioning
      phase of winery wastes subjected to vermicomposting.
AB  - A hazardous contaminant, 3,4-dichloroaniline (DCA) is widespread in the
      environment due to its extensive use in the manufacture of chemicals and its
      application in different sectors. The ability of fungi grow on in winery wastes
      in the preconditioning period of vermicomposting to degrade DCA was investigated.
      Three filamentous fungi (F1, F2, and F3) were isolated and one identified as
      Aspergillus niger and two as Fusarium sp. strains. The culture media with the
      fungus alone or in consortium (Fmix) with DCA as the nitrogen source were
      analyzed by solid-phase microextraction and gas chromatography-mass spectrometry
      (SPME-GC/MS). The fastest degradation rate was measured in Fmix with a DT50 of
      0.85day(-1). Fusarium sp. and A. niger differed in the metabolism of DCA. Five
      metabolites were identified as a result of oxidation, co-denitrification, N
      acetylation, and polymerization reactions. The major metabolites were 3,4
      dichloroacetanilide and dichloroquinolines. The azo-metabolites
      tetrachloroazobenzene and tetracloroazoxybenzene and 3,4-dichloronitrobenzene
      were found in minor amounts but appeared to be the most persistent in the
      Fusarium cultures (half-lives ranging from 8.3 to 30.9 days). This study
      highlights the metabolic potential of microorganisms in the preconditioning
      period of the vermicomposting process and its possible application for in situ
      bioremediation strategies. 

PMID- 24440654
TI  - Growth of streptomycetes in soil and their impact on bioremediation.
AB  - The impact of the extremely heavy metal resistant actinomycete Streptomyces
      mirabilis P16B-1 on heavy metal mobilization/stabilization, phytoremediation and
      stress level of plants was analyzed in the presence and absence of Sorghum
      bicolor in sterile microcosms containing highly metal contaminated or control
      soil. For control, a metal sensitive S. lividans TK24 was used. The metal
      contents with respect to the mobile and specifically adsorbed fractions of the
      contaminated soil were considerably decreased by addition of both, living and
      dead biomass of the strains, with the heavy metal resistant S. mirabilis P16B-1
      showing considerably higher impact. Both strains could grow in control soil,
      while only S. mirabilis P16B-1 formed new tip growth in the metal contaminated
      soil. A plant growth promoting effect was visible for S. mirabilis P16B-1 in
      contaminated soil enhancing the dry weight of inoculated Sorghum plants. Thus,
      metal resistant strains like S. mirabilis P16B-1 are able to enhance
      phytoremediation of heavy metal contaminated soils. 

PMID- 24440655
TI  - Role of Fe(III) in preventing humic interference during As(III) detection on gold
      electrode: spectroscopic and voltammetric evidence.
AB  - A drawback of As(III) detection using square wave anodic stripping voltammetry
      (SWASV) is that it is susceptible to interferences from various metals or organic
      compounds, especially in real sample water. This study attempts to understand the
      interference of co-existing of Fe(III) and humic acid (HA) molecules to the
      electrochemical detection of As(III) using Fourier transform infrared (FTIR)
      spectrum and X-ray photoelectron spectroscopy (XPS). The electrochemical
      experiments include stripping of As(III) in the solutions containing HA with
      different concentrations, cyclic voltammetry in 0.5M H2SO4 in the presence of HA
      or Fe(III) with/without addition of Fe(III) or HA, and stripping of As(III) in
      the presence of HA or Fe(III) with/without addition of Fe(III) or HA. FTIR and
      XPS are employed to confirm the affinity of HA to Fe(III) or As(III) in acidic
      condition. 

PMID- 24440656
TI  - Improving the prediction of chemotherapeutic sensitivity of tumors in breast
      cancer via optimizing the selection of candidate genes.
AB  - Estrogen receptor status and the pathologic response to preoperative chemotherapy
      are two important indicators of chemotherapeutic sensitivity of tumors in breast
      cancer, which are used to guide the selection of specific regimens for patients.
      Microarray-based gene expression profiling, which is successfully applied to the
      discovery of tumor biomarkers and the prediction of drug response, was suggested
      to predict the cancer outcomes using the gene signatures differentially expressed
      between two clinical states. However, many false positive genes unrelated to the
      phenotypic differences will be involved in the lists of differentially expressed
      genes (DEGs) when only using the statistical methods for gene selection, e.g.
      Student's t test, and subsequently affect the performance of the predictive
      models. For the purpose of improving the prediction of clinical outcomes, we
      optimized the selection of DEGs by using a combined strategy, for which the DEGs
      were firstly identified by the statistical methods, and then filtered by a
      similarity profiling approach that used for candidate gene prioritization. In our
      study, we firstly verified the molecular functions of the DEGs identified by the
      combined strategy with the gene expression data generated in the microarray
      experiments of Si-Wu-Tang, which is a popular formula in traditional Chinese
      medicine. The results showed that, for Si-Wu-Tang experimental data set, the
      cancer-related signaling pathways were significantly enriched by gene set
      enrichment analysis when using the DEG lists generated by the combined strategy,
      confirming the potentially cancer-preventive effect of Si-Wu-Tang. To verify the
      performance of the predictive models in clinical application, we used the
      combined strategy to select the DEGs as features from the gene expression data of
      the clinical samples, which were collected from the breast cancer patients, and
      constructed models to predict the chemotherapeutic sensitivity of tumors in
      breast cancer. After refining the DEG lists by a similarity profiling approach,
      the Matthew's correlation coefficients of predicting estrogen receptor status and
      the pathologic response to preoperative chemotherapy with the DEGs selected by
      the fold change ranking were 0.770 and 0.428, respectively, and were 0.748 and
      0.373 with the DEGs selected by SAM, respectively, which were generally higher
      than those achieved with unrefined DEG lists and those achieved by the candidate
      models in the second phase of Microarray Quality Control project (0.732 and
      0.301, respectively). Our results demonstrated that the strategy of integrating
      the statistical methods with the gene prioritization methods based on similarity
      profiling was a powerful tool for DEG selection, which effectively improved the
      performance of prediction models in clinical applications and can guide the
      personalized chemotherapy better. 

PMID- 24440657
TI  - Apes are intuitive statisticians.
AB  - Inductive learning and reasoning, as we use it both in everyday life and in
      science, is characterized by flexible inferences based on statistical
      information: inferences from populations to samples and vice versa. Many forms of
      such statistical reasoning have been found to develop late in human ontogeny,
      depending on formal education and language, and to be fragile even in adults. New
      revolutionary research, however, suggests that even preverbal human infants make
      use of intuitive statistics. Here, we conducted the first investigation of such
      intuitive statistical reasoning with non-human primates. In a series of 7
      experiments, Bonobos, Chimpanzees, Gorillas and Orangutans drew flexible
      statistical inferences from populations to samples. These inferences,
      furthermore, were truly based on statistical information regarding the relative
      frequency distributions in a population, and not on absolute frequencies.
      Intuitive statistics in its most basic form is thus an evolutionarily more
      ancient rather than a uniquely human capacity. 

PMID- 24440658
TI  - Inducible intestine-specific deletion of Kruppel-like factor 5 is characterized
      by a regenerative response in adult mouse colon.
AB  - Kruppel-like factor 5 (KLF5) is a pro-proliferative transcriptional regulator
      primarily expressed in the intestinal crypt epithelial cells. Constitutive
      intestine-specific deletion of Klf5 is neonatal lethal suggesting a crucial role
      for KLF5 in intestinal development and homeostasis. We have previously shown Klf5
      to play an active role regulating intestinal tumorigenesis. Here we examine the
      effect of inducible intestine-specific deletion of Klf5 in adult mice. Klf5 is
      lost from the intestine beginning at day 3 after the start of a 5-day treatment
      with the inducer tamoxifen. Although the mice have no significant weight loss or
      lethality, the colonic tissue shows signs of epithelial distress starting at day
      3 following induction. Accompanying the morphological changes is a significant
      loss of proliferative crypt epithelial cells as revealed by BrdU or Ki67 staining
      at days 3 and 5 after start of tamoxifen. We also observed a loss of goblet cells
      from the colon and Paneth cells from the small intestine upon induced deletion of
      Klf5. In addition, loss of Klf5 from the colonic epithelium is accompanied by a
      regenerative response that coincides with an expansion in the zone of Sox9
      expression along the crypt axis. At day 11, both proliferation and Sox9
      expression return to baseline levels. Microarray and quantitative PCR analyses
      reveal an up-regulation of several regeneration-associated genes (Reg1A, Reg3G
      and Reg3B) and down-regulation of many Klf5 targets (Ki-67, cyclin B, Cdc2 and
      cyclin D1). Sox9 and Reg1A protein levels are also increased upon Klf5 loss.
      Lentiviral-mediated knockdown of KLF5 and exogenous expression of KLF5 in
      colorectal cancer cell lines confirm that Sox9 expression is negatively regulated
      by KLF5. Furthermore, ChIP assays reveal a direct association of KLF5 with both
      the Sox9 and Reg1A promoters. We have shown that disruption of epithelial
      homeostasis due to Klf5 loss from the adult colon is followed by a regenerative
      response led by Sox9 and the Reg family of proteins. Our study demonstrates that
      adult mouse colonic tissue undergoes acute physiological changes to accommodate
      the loss of Klf5 withstanding epithelial damage further signifying importance of
      Klf5 in colonic homeostasis. 

PMID- 24440659
TI  - Phase I and extension study of clofarabine plus cyclophosphamide in patients with
      relapsed/refractory acute lymphoblastic leukemia.
AB  - BACKGROUND: Clofarabine is a nucleoside analogue with activity in children with
      acute lymphoblastic leukemia (ALL). Based on the hypothesis that clofarabine
      inhibits DNA repair after exposure to DNA-damaging agents, we designed a phase I
      and extension study to evaluate the combination of clofarabine and
      cyclophosphamide in adult patients with relapsed/refractory ALL. METHODS: The
      continual reassessment method (CRM) was used to define the maximum tolerated dose
      (MTD). RESULTS: Fifty patients with a median age of 30 years (range, 21-72 years)
      were enrolled, 30 of whom were part of the phase I group. Clofarabine 40 mg/m(2)
      intravenously daily * 3 days and cyclophosphamide 200 mg/m(2) intravenously every
      12 hours * 3 days were established as the MTDs. Dose limiting toxicity (DLT)
      included diarrhea, transaminase elevations, and skin rashes. The response rate of
      the whole study group was 14%, including 10% of patients who achieved complete
      remission (CR) or CR without platelet recovery (CRp). Three responses occurred in
      patients with primary refractory disease. Early mortality (< 30 days) was 6%. The
      median duration of response was 69 days (range, 5-315 days). Median overall
      survival was about 3 months. Compared with day 1 (cyclophosphamide alone), H2AX
      phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were
      administered as a couplet (n = 8). CONCLUSION: The combination of clofarabine
      plus cyclophosphamide at the doses used in this study in a group of heavily
      pretreated patients with ALL is only moderately effective. Other doses,
      alternative schedules, or a more favorable patient population may achieve better
      results.

PMID- 24440661
TI  - Cholesterol favors the anchorage of human dystrophin repeats 16 to 21 in membrane
      at physiological surface pressure.
AB  - Dystrophin (DYS) is a filamentous protein that connects the cytoskeleton and the
      extracellular matrix via the sarcolemma, conferring resistance to muscular cells.
      In this study, interactions between the DYS R16-21 fragment and lipids were
      examined using Langmuir films made of anionic and zwitterionic lipids. The film
      fluidity was modified by the addition of 15% cholesterol. Whatever the lipid
      mixture examined, at low surface pressure (20 mN/m) few differences appeared on
      the protein insertion and the presence of cholesterol did not affect the
      protein/lipid interactions. At high surface pressure (30 mN/m), the protein
      insertion was very low and occurred only in zwitterionic films in the liquid
      expanded phase. In anionic films, electrostatic interactions prevented the
      protein insertion outright, and caused accumulation of the protein on the
      hydrophilic part of the monolayer. Addition of cholesterol to both lipid mixtures
      drastically modified the protein-lipid interactions: the DYS R16-21 insertion
      increased and its organization in the monolayer appeared to be more homogeneous.
      The presence of accessible cholesterol recognition amino-acid consensus sequences
      in this fragment may enhance the protein/membrane binding at physiological
      lateral pressure. These results suggest that the anchorage of dystrophin to the
      membrane in vivo may be stabilized by cholesterol-rich nano-domains in the inner
      leaflet of sarcolemma.

PMID- 24440660
TI  - Characterization of the water defect at the HIV-1 gp41 membrane spanning domain
      in bilayers with and without cholesterol using molecular simulations.
AB  - The membrane spanning domain (MSD) of human immunodeficiency virus 1 (HIV-1)
      envelope glycoprotein gp41 is important for fusion and infection. We used
      molecular dynamics (MD) simulations (3.4 MUs total) to relate membrane and
      peptide properties that lead to water solvation of the alpha-helical gp41 MSD's
      midspan arginine in pure dipalmitoylphosphatidylcholine (DPPC) and in 50/50
      DPPC/cholesterol membranes. We find that the midspan arginine is solvated by
      water that penetrates the inner leaflet, leading to a so-called water defect. The
      water defect is surprisingly robust across initial conditions and membrane
      compositions, but the presence of cholesterol modulates its behavior in several
      key ways. In the cholesterol-containing membranes, fluctuations in membrane
      thickness and water penetration depth are localized near the midspan arginine,
      and the MSD helices display a tightly regulated tilt angle. In the cholesterol
      free membranes, thickness fluctuations are not as strongly correlated to the
      peptide position and tilt angles vary significantly depending on protein position
      relative to boundaries between domains of differing thickness. Cholesterol in an
      HIV-1 viral membrane is required for infection. Therefore, this work suggests
      that the colocalized water defect and membrane thickness fluctuations in
      cholesterol-containing viral membranes play an important role in fusion by
      bringing the membrane closer to a stability limit that must be crossed for fusion
      to occur.

PMID- 24440662
TI  - Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic
      mice by PEGylated calcium phosphate hybrid micelles.
AB  - Efficient systems for delivery of small interfering RNA (siRNA) are required for
      clinical application of RNA interference (RNAi) in cancer therapy. Herein, we
      developed a safe and efficient nanocarrier comprising poly(ethylene glycol)-block
      charge-conversional polymer (PEG-CCP)/calcium phosphate (CaP) hybrid micelles for
      systemic delivery of siRNA and studied their efficacy in spontaneous
      bioluminescent pancreatic tumors from transgenic mice. PEG-CCP was engineered to
      provide the siRNA-loaded hybrid micelles with enhanced colloidal stability and
      biocompatibility due to the PEG capsule and with endosome-disrupting
      functionality due to the acidic pH-responsive CCP segment where the polyanionic
      structure could be converted to polycationic structure at acidic pH through cis
      aconitic amide cleavage. The resulting hybrid micelles were confirmed to have a
      diameter of <50nm, with a narrow size distribution. Intravenously injected hybrid
      micelles significantly reduced the luciferase-based luminescent signal from the
      spontaneous pancreatic tumors in an siRNA sequence-specific manner. The gene
      silencing activity of the hybrid micelles correlated with their preferential
      tumor accumulation, as indicated by fluorescence imaging and histological
      analysis. Moreover, there were no significant changes in hematological parameters
      in mice treated with the hybrid micelles. These results demonstrate the great
      potential of the hybrid micelles as siRNA carriers for RNAi-based cancer therapy.

PMID- 24440663
TI  - Heat-activated thermosensitive liposomal cisplatin (HTLC) results in effective
      growth delay of cervical carcinoma in mice.
AB  - Cisplatin (CDDP) has been identified as the primary chemotherapeutic agent for
      the treatment of cervical cancer, but dose limiting toxicity is a key issue
      associated with its clinical application. A suite of liposome formulations of
      CDDP has been developed in efforts to reduce systemic toxicity, but their
      therapeutic advantage over the free drug has been modest due to insufficient drug
      release at the tumor site. This report describes the development of a novel heat
      activated thermosensitive liposome formulation containing CDDP (HTLC) designed to
      release approximately 90% of the loaded drug in less than 5min under mild heating
      conditions (42 degrees C). Physico-chemical characteristics of HTLC were assessed
      in terms of gel to liquid crystalline phase transition temperature (Tm), drug
      loading efficiency, particle size, and stability. The pharmacokinetic profile and
      biodistribution of HTLC in non-tumor-bearing mice were evaluated over a 24h
      period. A sophisticated spatio-temporal elucidation of HTLC release in tumor
      bearing mice was achieved by way of real-time monitoring using a magnetic
      resonance (MR) imaging protocol, wherein a custom-built laser-based conformal
      heat source was applied at the tumor volume to trigger the release of HTLC co
      encapsulated with the MR contrast agent gadoteridol (Gd-HP-DO3A). MR thermometry
      (MRT) demonstrated that a relatively uniform temperature distribution was
      achieved in the tumor volume using the external laser-based heating setup. In
      mice bearing subcutaneously-implanted ME-180 cervical tumors, the combination of
      HTLC and heat resulted in a 2-fold increase in tumor drug levels at 1h post
      administration compared to HTLC without heating. Furthermore, the overall tumor
      accumulation levels for the HTLC groups (with and without heat) at 1h post
      injection were significantly higher than the corresponding free CDDP group. This
      translated into a significant improvement in therapeutic efficacy evaluated as
      tumor growth delay (p<0.05) for the heated HTLC treatment group compared to the
      unheated HTLC, heated or unheated free CDDP, and saline groups. Overall, findings
      from this study demonstrate that a heat-activated, triggered release formulation
      of CDDP results in a significant enhancement in the therapeutic index of this
      drug. 

PMID- 24440665
TI  - Facts, fallacies and future of dissolution testing of polysaccharide based colon
      specific drug delivery.
AB  - Colonic diseases like ulcerative colitis, Crohn's disease, and colon cancer are
      on rise due to variations in the dietary and lifestyle habits. Increase in
      prevalence of such diseases has augmented the interest of researchers in colon
      targeted drug delivery systems. Polysaccharide coating has emerged as one of the
      most successful approaches in this direction. Evaluation of such systems,
      however, demands an efficient dissolution method in terms of convenience,
      economy, relevance and reproducibility. It is problematic to mimic the dynamic
      and ecologically diverse features of the colon. A number of dissolution
      approaches were tried which include incorporation of polysaccharide-degrading
      enzymes, rat caecal contents, human faecal slurries, and multi-stage culture
      systems. Till date, pursuit for cost-effective and animal-sparing colon-specific
      bio-relevant dissolution media has been a foremost challenge facing
      pharmaceutical scientists over many decades. This article reviews various
      dissolution methods adopted to mimic the in vivo performance of dosage forms that
      are used for colon targeting. It also highlights limitations of the available
      methods and conditions that should be taken into account while designing a bio
      relevant dissolution method for such systems. 

PMID- 24440664
TI  - Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus
      barrier.
AB  - Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus
      barrier in the airway in order to overcome rapid mucociliary clearance and reach
      the underlying epithelium; however, even the most widely used viral gene carriers
      are unable to efficiently do so. We developed two polymeric gene carriers that
      compact plasmid DNA into small and highly stable nanoparticles with dense
      polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG
      coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex
      vivo and mouse airway mucus ex situ. Intranasal administration of the mucus
      penetrating DNA nanoparticles greatly enhanced particle distribution, retention
      and gene transfer in the mouse lung airways compared to conventional gene
      carriers. Successful delivery of a full-length plasmid encoding the cystic
      fibrosis transmembrane conductance regulator protein was achieved in the mouse
      lungs and airway cells, including a primary culture of mucus-covered human airway
      epithelium grown at air-liquid interface, without causing acute inflammation or
      toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for
      lung gene therapy. 

PMID- 24440666
TI  - Basic life support trained nurses ventilate more efficiently with laryngeal mask
      supreme than with facemask or laryngeal tube suction-disposable--a prospective,
      randomized clinical trial.
AB  - OBJECTIVE: In some emergency situations resuscitation and ventilation may have to
      be performed by basic life support trained personnel, especially in rural areas
      where arrival of advanced life support teams can be delayed. The use of advanced
      airway devices such as endotracheal intubation has been deemphasized for
      basically-trained personnel, but it is unclear whether supraglottic airway
      devices are advisable over traditional mask-ventilation. METHODS: In this
      prospective, randomized clinical single-centre trial we compared airway
      management and ventilation performed by nurses using facemask, laryngeal mask
      Supreme (LMA-S) and laryngeal tube suction-disposable (LTS-D). Basic life support
      trained nurses (n=20) received one-hour practical training with each device. ASA
      1-2 patients scheduled for elective surgery were included (n=150). After
      induction of anaesthesia and neuromuscular block nurses had two 90-second
      attempts to manage the airway and ventilate the patient with volume-controlled
      ventilation. RESULTS: Ventilation failed in 34% of patients with facemask, 2%
      with LMA-S and 22% with LTS-D (P<0.001). In patients who could be ventilated
      successfully mean tidal volume was 240+/-210 ml with facemask, 470+/-120 ml with
      LMA-S and 470+/-140 ml with LTS-D (P<0.001). Leak pressure was lower with LMA-S
      (23.3+/-10.8 cm H2O, 95% CI 20.2-26.4) than with LTS-D (28.9+/-13.9 cm.H2O, 95%
      CI 24.4-33.4; P=0.047). CONCLUSIONS: After one hour of introductory training,
      nurses were able to use LMA-S more effectively than facemask and LTS-D. High
      ventilation failure rates with facemask and LTS-D may indicate that additional
      training is required to perform airway management adequately with these devices.
      High-level trials are needed to confirm these results in cardiac arrest patients.

PMID- 24440667
TI  - Galphaq signalling: the new and the old.
AB  - In the last few years the interactome of Galphaq has expanded considerably,
      contributing to improve our understanding of the cellular and physiological
      events controlled by this G alpha subunit. The availability of high-resolution
      crystal structures has led the identification of an effector-binding region
      within the surface of Galphaq that is able to recognise a variety of effector
      proteins. Consequently, it has been possible to ascribe different Galphaq
      functions to specific cellular players and to identify important processes that
      are triggered independently of the canonical activation of phospholipase Cbeta
      (PLCbeta), the first identified Galphaq effector. Novel effectors include
      p63RhoGEF, that provides a link between G protein-coupled receptors and RhoA
      activation, phosphatidylinositol 3-kinase (PI3K), implicated in the regulation of
      the Akt pathway, or the cold-activated TRPM8 channel, which is directly inhibited
      upon Galphaq binding. Recently, the activation of ERK5 MAPK by Gq-coupled
      receptors has also been described as a novel PLCbeta-independent signalling axis
      that relies upon the interaction between this G protein and two novel effectors
      (PKCzeta and MEK5). Additionally, the association of Galphaq with different
      regulatory proteins can modulate its effector coupling ability and, therefore,
      its signalling potential. Regulators include accessory proteins that facilitate
      effector activation or, alternatively, inhibitory proteins that downregulate
      effector binding or promote signal termination. Moreover, Galphaq is known to
      interact with several components of the cytoskeleton as well as with important
      organisers of membrane microdomains, which suggests that efficient signalling
      complexes might be confined to specific subcellular environments. Overall, the
      complex interaction network of Galphaq underlies an ever-expanding functional
      diversity that puts forward this G alpha subunit as a major player in the control
      of physiological functions and in the development of different pathological
      situations. 

PMID- 24440668
TI  - Regulation of chondrogenesis by protein kinase C: Emerging new roles in calcium
      signalling.
AB  - During chondrogenesis, complex intracellular signalling pathways regulate an
      intricate series of events including condensation of chondroprogenitor cells and
      nodule formation followed by chondrogenic differentiation. Reversible
      phosphorylation of key target proteins is of particular importance during this
      process. Among protein kinases known to be involved in these pathways, protein
      kinase C (PKC) subtypes play pivotal roles. However, the precise function of PKC
      isoenzymes during chondrogenesis and in mature articular chondrocytes is still
      largely unclear. In this review, we provide a historical overview of how the
      concept of PKC-mediated chondrogenesis has evolved, starting from the first
      discoveries of PKC isoform expression and activity. Signalling components
      upstream and downstream of PKC, leading to the stimulation of chondrogenic
      differentiation, are also discussed. Although it is evident that we are only at
      the beginning to understand what roles are assigned to PKC subtypes during
      chondrogenesis and how they are regulated, there are many yet unexplored aspects
      in this area. There is evidence that calcium signalling is a central regulator in
      differentiating chondroprogenitors; still, clear links between intracellular
      calcium signalling and prototypical calcium-dependent PKC subtypes such as
      PKCalpha have not been established. Exploiting putative connections and shedding
      more light on how exactly PKC signalling pathways influence cartilage formation
      should open new perspectives for a better understanding of healthy as well as
      pathological differentiation processes of chondrocytes, and may also lead to the
      development of novel therapeutic approaches. 

PMID- 24440669
TI  - Synthesis and characterization of curcumin loaded polymer/lipid based
      nanoparticles and evaluation of their antitumor effects on MCF-7 cells.
AB  - BACKGROUND: Hybrid materials are synthesized using hydrophilic polymer and lipids
      which ensure their long term systemic circulation through intravenous
      administration and enhance loading of hydrophobic drugs. The purpose of this
      study is to prepare, characterize and evaluate the in vitro efficacy of curcumin
      loaded poly-hydroxyethyl methacrylate/stearic acid nanoparticles in MCF-7.
      METHODS: C-PSA-NPs, prepared using the emulsification-solvent evaporation method
      were characterized by dynamic laser scattering, SEM, AFM, FT-IR, X-ray
      diffraction, and TGA. The in vitro release behavior was observed in PBS pH7.4,
      the anticancer potential was analyzed by MTT assay, cell cycle and apoptosis
      studies were performed through flow cytometry. C-PSA-NPs drug localization and
      cancer cell morphological changes were analyzed in MCF-7 cell line. RESULTS: C
      PSA-NPs exhibited the mean particle size in the range of 184nm with no
      aggregation. The surface charge of the material was around -29.3mV. Thermal
      studies (TGA) and surface chemistry studies (FT-IR, XRD) showed the existence of
      drug curcumin in C-PSA-NPs. The MTT assay indicated higher anticancer properties
      and flow cytometry studies revealed that there were better apoptotic activity and
      maximum localization of C-PSA-NPs than curcumin. CONCLUSIONS: Polymer lipid based
      drug delivery appeared as one of the advancements in drug delivery systems.
      Through the present study, a novel polymer lipid based nanocarrier delivery
      system loaded with curcumin was demonstrated as an effective and potential
      alternative method for tumor treatment in MCF-7 cell line. GENERAL SIGNIFICANCE:
      C-PSA-NPs exhibited potent anticancer activity in MCF-7 cell line and it
      indicates that C-PSA-NPs are a suitable carrier for curcumin.

PMID- 24440670
TI  - Hypobaric hypoxia induced arginase expression limits nitric oxide availability
      and signaling in rodent heart.
AB  - BACKGROUND: This study was aimed to evaluate regulation of cardiac arginase
      expression during hypobaric hypoxia and subsequent effect on nitric oxide
      availability and signaling. METHODS: Rats were exposed to hypobaric hypoxia
      (282mmHg for 3h) and ARG1 expression was monitored. The expression levels of eNOS
      and eNOS(Ser1177) were determined by Western blotting, cGMP levels were measured
      by ELISA and amino acid concentrations were measured by HPLC analysis.
      Transcription regulation of arginase was monitored by chromatin
      immunoprecipitation (ChIP) assay with anti-c-Jun antibody for AP-1 consensus
      binding site on ARG1 promoter. Arginase activity was inhibited by intra-venous
      dose of N-(omega)-hydroxy-nor-l-arginine (nor-NOHA) prior to hypoxia exposure and
      subsequent effect on NO availability and oxidative stress were evaluated.
      RESULTS: Hypobaric hypoxia induced cardiac arginase expression by recruiting c
      Jun to AP-1 binding site on ARG1 promoter. This increased expression redirected l
      arginine towards arginase and resulted in limited endothelial nitric oxide
      synthase (eNOS) activity, nitric oxide (NO) availability and cGMP mediated
      signaling. Inhibition of arginase restored the eNOS activity, promoted cardiac NO
      availability and ameliorated peroxynitrite formation during hypoxia. CONCLUSIONS:
      Hypoxic induced arginase under transcription control of AP-1 reciprocally
      regulates eNOS activity and NO availability in the heart. This also results in
      cardiac oxidative stress. GENERAL SIGNIFICANCE: This study provides understanding
      of hypoxia-mediated transcriptional regulation of arginase expression in the
      heart and its subsequent effect on eNOS activity, NO availability and signaling
      as well as cardiac oxidative stress. This information will support the use of
      arginase inhibitors as therapeutics for pathological hypoxia.

PMID- 24440671
TI  - Interactions between the intestinal microbiome and liver diseases.
AB  - The human intestine harbors a diverse community of microbes that promote
      metabolism and digestion in their symbiotic relationship with the host.
      Disturbance of its homeostasis can result in disease. We review factors that
      disrupt intestinal homeostasis and contribute to nonalcoholic fatty liver
      disease, steatohepatitis, alcoholic liver disease, and cirrhosis. Liver disease
      has long been associated with qualitative and quantitative (overgrowth) dysbiotic
      changes in the intestinal microbiota. Extrinsic factors, such as the Western diet
      and alcohol, contribute to these changes. Dysbiosis results in intestinal
      inflammation, a breakdown of the intestinal barrier, and translocation of
      microbial products in animal models. However, the contribution of the intestinal
      microbiome to liver disease goes beyond simple translocation of bacterial
      products that promote hepatic injury and inflammation. Microbial metabolites
      produced in a dysbiotic intestinal environment and host factors are equally
      important in the pathogenesis of liver disease. We review how the combination of
      liver insult and disruptions in intestinal homeostasis contribute to liver
      disease.

PMID- 24440672
TI  - Budesonide is more effective than mesalamine or placebo in short-term treatment
      of collagenous colitis.
AB  - BACKGROUND & AIMS: Studies reporting that budesonide is effective for the
      treatment of collagenous colitis have been small and differed in efficacy
      measures. Mesalamine has been proposed as a treatment option for collagenous
      colitis, although its efficacy has never been investigated in placebo-controlled
      trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate
      budesonide and mesalamine as short-term treatments for collagenous colitis.
      METHODS: Patients with active collagenous colitis were randomly assigned to
      groups given pH-modified release oral budesonide capsules (9 mg budesonide once
      daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily,
      Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double
      dummy fashion. The study was conducted in 31 centers (hospital clinics and
      private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom.
      The primary end point was clinical remission at 8 weeks defined as <= 3 stools
      per day. Secondary end points included clinical remission at 8 weeks, according
      to the Hjortswang-Criteria of disease activity, taking stool consistency into
      account. RESULTS: A greater percentage of patients in the budesonide group were
      in clinical remission at week 8 than the placebo group (intention-to-treat
      analysis, 80.0% vs 59.5%; P = .072; per-protocol analysis, 84.8% vs 60.6%; P =
      .046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide
      achieved clinical remission compared with 37.8% of patients given placebo (P =
      .0006); 44.0% of patients given mesalamine achieved clinical remission, but
      budesonide was superior to mesalamine (P = .0035). Budesonide significantly
      improved stool consistency and mucosal histology, and alleviated abdominal pain.
      The rate of adverse events did not differ among groups. CONCLUSIONS: Oral
      budesonide (9 mg once daily) is effective and safe for short-term treatment of
      collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily)
      appears to be ineffective. ClinicalTrials.gov number, NCT00450086.

PMID- 24440673
TI  - Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and
      humans.
AB  - BACKGROUND & AIMS: There are no robust noninvasive methods for colorectal cancer
      screening and diagnosis. Metabolomic and gene expression analyses of urine and
      tissue samples from mice and humans were used to identify markers of colorectal
      carcinogenesis. METHODS: Mass spectrometry-based metabolomic analysis of urine
      and tissues from wild-type C57BL/6J and Apc(Min/+) mice, as well as from mice
      with azoxymethane-induced tumors, was employed in tandem with gene expression
      analysis. Metabolic profiling was also performed on colon tumor and adjacent
      nontumor tissues from 39 patients. The effects of beta-catenin activity on
      metabolic profiles were assessed in mice with colon-specific disruption of Apc.
      RESULTS: Thirteen markers were found in urine associated with development of
      colorectal tumors in Apc(Min/+) mice. Metabolites related to polyamine
      metabolism, nucleic acid metabolism, and methylation, identified tumor-bearing
      mice with 100% accuracy, and also accurately identified mice with polyps. Changes
      in gene expression in tumor samples from mice revealed that derangement of
      metabolites were a reflection of coordinate metabolic reprogramming in tumor
      tissue. Similar changes in urinary metabolites were observed in mice with
      azoxymethane-induced tumors and in mice with colon-specific activation of beta
      catenin. The metabolic alterations indicated by markers in urine, therefore,
      appear to occur during early stages of tumorigenesis, when cancer cells are
      proliferating. In tissues from patients, tumors had stage-dependent increases in
      17 metabolites associated with the same metabolic pathways identified in mice.
      Ten metabolites that were increased in tumor tissues, compared with nontumor
      tissues (proline, threonine, glutamic acid, arginine, N1-acetylspermidine,
      xanthine, uracil, betaine, symmetric dimethylarginine, and asymmetric
      dimethylarginine), were also increased in urine from tumor-bearing mice.
      CONCLUSIONS: Gene expression and metabolomic profiles of urine and tissue samples
      from mice with colorectal tumors and of colorectal tumor samples from patients
      revealed pathways associated with derangement of specific metabolic pathways that
      are indicative of early-stage tumor development. These urine and tissue markers
      might be used in early detection of colorectal cancer.

PMID- 24440675
TI  - Vertical cross-sectional imaging of colonic dysplasia in vivo with multi-spectral
      dual axes confocal endomicroscopy.

PMID- 24440676
TI  - Physician modification of Gore C3 excluder endograft for treatment of abdominal
      aortic aneurysms anatomically unsuitable for conventional endovascular repair.
AB  - Until recently, the Cook Zenith aortic endograft (Cook Medical Inc, Bloomington,
      Ind) was the only device used for physician-modified fenestration because its
      constraining wire allowed physicians to reconstrain the device after
      modifications. Although the Cook Zenith fenestrated endograft has been approved
      by the Food and Drug Administration, it is currently not available in the
      majority of the hospitals and is not applicable to the patients who need urgent
      or emergent aneurysm repair. With the redesign of the Gore C3 delivery system,
      the Gore Excluder aortic stent graft (W. L. Gore & Associates, Inc, Flagstaff,
      Ariz) can now also be reconstrained, which makes it suitable for physician
      modified fenestration. We describe the technique for modification and
      implantation of the Gore Excluder aortic stent graft in a patient requiring 2
      vessel bilateral renal artery fenestration. This application provides an
      additional option for treatment of patients with abdominal aortic aneurysms who
      are anatomically unsuitable for conventional endovascular aneurysm repair and are
      at high risk for open repair. 

PMID- 24440674
TI  - A histologic scoring system for prognosis of patients with alcoholic hepatitis.
AB  - BACKGROUND & AIMS: There is no histologic classification system to determine
      prognoses of patients with alcoholic hepatitis (AH). We identified histologic
      features associated with disease severity and created a histologic scoring system
      to predict short-term (90-day) mortality. METHODS: We analyzed data from 121
      patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from
      January 2000 to January 2008 with features of AH and developed a histologic
      scoring system to determine the risk of death using logistic regression. The
      system was tested and updated in a test set of 96 patients from 5 academic
      centers in the United States and Europe, and a semiquantitative scoring system
      called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system
      was validated in an independent set of 109 patients. Interobserver agreement was
      evaluated by weighted kappa statistical analysis. RESULTS: The degree of
      fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and
      presence of megamitochondria were independently associated with 90-day mortality.
      We used these 4 parameters to develop the AHHS to identify patients with a low (0
      3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90
      days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day
      mortality in the training and test sets with an area under the receiver operating
      characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater
      agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for
      neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type
      of bilirubinostasis predicted the development of bacterial infections.
      CONCLUSIONS: We identified histologic features associated with the severity of AH
      and developed a patient classification system that might be used in clinical
      decision making.

PMID- 24440677
TI  - A limited and customized follow-up seems justified after endovascular abdominal
      aneurysm repair in octogenarians.
AB  - OBJECTIVE: The objective of this study was to determine whether long-term follow
      up after endovascular aneurysm repair (EVAR) is justified in octogenarians.
      METHODS: Between September 1996 and October 2011, all patients, including
      octogenarians, treated for an abdominal aortic aneurysm (AAA) by EVAR were
      included in a prospective database. Patients older than 80 years and with a
      nonruptured infrarenal aneurysm treated electively or urgently were included in
      the study (study group [SG]). Patients with ruptured aneurysms and patients who
      died during surgery or within the first postoperative month were excluded from
      further analysis. The control group (CG) consisted of patients younger than 80
      years, matched for gender and AAA diameter. All patients were evaluated 4 to 8
      weeks after EVAR and then annually thereafter. Follow-up data were complemented
      by review of the computerized hospital registry and charts and by contact of the
      patient's general practitioner or referring hospital. Primary outcomes were stent
      or aneurysm-related complications and interventions. Secondary outcomes were
      additional surgical complications and patient survival. RESULTS: A total number
      of 193 patients (SG, n = 97; CG, n = 96) were included for analysis. Median age
      was 80 years, and 88.6% were male. Median follow-up time was 33.6 months
      (interquartile range [IQR], 12.9-68.3). Stent- and procedure-related
      postoperative complications were comparable between groups (SG, 41.2%; CG, 39.6%;
      P = .82). Median time to complication was 2.3 months (IQR, 0.2-19.4) in the SG
      compared with 18.1 months (IQR, 6.8-50.5) in the CG. The 2-year complication-free
      survival rates were 58% (SG) and 60% (CG). Interventions were performed
      significantly less frequently in octogenarians (SG, 8.2%; CG, 19.8%; P < .05).
      Median time to intervention was 11.1 months (IQR, 2.0-31.0) in the SG compared
      with 54.3 months (IQR, 15.0-93.2) in the CG. The 2-year intervention-free
      survival rates were 90% (SG) and 92% (CG). During follow-up, 98 patients died
      (SG, n = 54; CG, n = 44); median time to death was 31.8 months (IQR, 13.3-66.0)
      in the SG compared with 44.4 months (IQR, 15.0-77.7) in the CG. One aneurysm
      related death occurred in the CG. The 2- and 5-year survival rates were 71% and
      32% for the SG compared with 77% and 66% for the CG (P < .05). CONCLUSIONS:
      Because of the low incidence of secondary procedures and AAA-related deaths in
      octogenarians, long-term and frequent follow-up after EVAR seems questionable. An
      adapted and shortened follow-up seems warranted in this patient group.

PMID- 24440678
TI  - A multicenter, randomized, controlled trial of totally percutaneous access versus
      open femoral exposure for endovascular aortic aneurysm repair (the PEVAR trial).
AB  - OBJECTIVE: The first multicenter randomized controlled trial was designed and
      conducted to assess the safety and effectiveness of totally percutaneous
      endovascular aortic aneurysm repair (PEVAR) with use of a 21F endovascular stent
      graft system and either an 8 F or 10 F suture-mediated closure system (the PEVAR
      trial, NCT01070069). A noninferiority trial design was chosen to compare
      percutaneous access with standard open femoral exposure. METHODS: Between 2010
      and 2012, 20 U.S. institutions participated in a prospective, Food and Drug
      Administration-approved randomized trial to evaluate percutaneous femoral artery
      access and closure by a "preclose" technique in conjunction with endovascular
      abdominal aortic aneurysm repair. A total of 151 patients were allocated by a 2:1
      design to percutaneous access/closure (n = 101) or open femoral exposure (n = 50
      [FE]). PEVAR procedures were performed with either the 8 F Perclose ProGlide (n =
      50 [PG]) or the 10 F Prostar XL (n = 51 [PS]) closure devices. All endovascular
      abdominal aortic aneurysm repair procedures were performed with the Endologix 21
      F profile (outer diameter) sheath-based system. Patients were screened by
      computed tomography with three-dimensional reconstruction and independent
      physician review for anatomic suitability and adequate femoral artery anatomy for
      percutaneous access. The primary trial end point (treatment success) was defined
      as procedural technical success and absence of major adverse events and vascular
      complications at 30 days. An independent access closure substudy evaluated major
      access-related complications. Clinical utility and procedural outcomes, ankle
      brachial index, blood laboratory analyses, and quality of life were also
      evaluated with continuing follow-up to 6 months. RESULTS: Baseline
      characteristics were similar among groups. Procedural technical success was 94%
      (PG), 88% (PS), and 98% (FE). One-month primary treatment success was 88% (PG),
      78% (PS), and 78% (FE), demonstrating noninferiority vs FE for PG (P = .004) but
      not for PS (P = .102). Failure rates in the access closure substudy analyses
      demonstrated noninferiority of PG (6%; P = .005), but not of PS (12%; P = .100),
      vs FE (10%). Compared with FE, PG and PS yielded significantly shorter times to
      hemostasis and procedure completion and favorable trends in blood loss, groin
      pain, and overall quality of life. Initial noninferiority test results persist to
      6 months, and no aneurysm rupture, conversion to open repair, device migration,
      or stent graft occlusion occurred. CONCLUSIONS: Among trained operators, PEVAR
      with an adjunctive preclose technique using the ProGlide closure device is safe
      and effective, with minimal access-related complications, and it is noninferior
      to standard open femoral exposure. Training, experience, and careful application
      of the preclose technique are of paramount importance in ensuring successful,
      sustainable outcomes.

PMID- 24440680
TI  - Discussion.

PMID- 24440679
TI  - Effect of antifibrinolytic therapy with tranexamic acid on abdominal aortic
      aneurysm shrinkage after endovascular repair.
AB  - OBJECTIVE: The long-term outcomes of endovascular abdominal aortic aneurysm
      repair (EVAR) remain to be determined, but patients with aneurysm shrinkage after
      EVAR appear to have a good prognosis. We previously observed that antiplatelet
      therapy is a risk factor for lack of aneurysm shrinkage, a finding suggesting
      that coagulation and fibrinolysis play roles in shrinkage. We therefore studied
      the effect of antifibrinolytic therapy with tranexamic acid (TXA) on aneurysm
      shrinkage after EVAR. METHODS: From May 2007 to May 2012, EVAR was performed in
      187 patients, 165 of whom had an enhanced computed tomographic evaluation 6
      months after their procedure. Six of the 165 patients were excluded from the
      study because they had a type Ia endoleak or coil embolization to treat a type II
      endoleak <= 6 months after EVAR. Of the remaining 159 patients, 110 underwent
      EVAR before we started to use TXA in our centers. TXA therapy (1500 mg/d for 6
      months) began in January 2011, and 48 patients completed the treatment regimen.
      Patients not treated with TXA were compared with those given TXA. Analyses to
      identify risk factors for lack of aneurysm shrinkage were performed. RESULTS: No
      patient had a thromboembolic event. There were no significant differences between
      the no-TXA and TXA groups in demographics, aneurysm characteristics, prosthesis
      implanted, type II endoleak occurrence during EVAR or 1 or 6 months afterward, or
      aneurysm shrinkage at 1 month. However, at 6 months after EVAR, the TXA group had
      significantly greater aneurysm shrinkage (P = .035) and a significantly higher
      percentage of patients with >4 mm in shrinkage (P = .010). Multiple regression
      analysis showed aneurysm diameter, type II endoleak 6 months after EVAR, and TXA
      treatment were independently associated with aneurysm shrinkage or lack of
      shrinkage. CONCLUSIONS: Antifibrinolytic therapy with TXA was associated with
      aneurysm shrinkage after EVAR. Studies to identify the dosage of TXA that is
      optimally safe and effective in this application, as well as investigations of
      the best timing and route (parenteral vs oral) for TXA administration, are
      warranted.

PMID- 24440681
TI  - The LRP1-independent mechanism of PAI-1-induced migration in CpG-ODN activated
      macrophages.
AB  - CpG-oligodeoxynucleotides (CpG-ODNs) induces plasminogen activator inhibitor type
      1 (PAI-1) expression in macrophages, leading to enhanced migration through
      vitronectin. However, the precise role of low-density lipoprotein receptor
      related protein 1 (LRP1) in PAI-1 induced migration of macrophages in the
      inflammatory environment is not known. In this study, we elucidated a novel
      mechanism describing the altered role of LRP1 in macrophage migration depending
      on the activation state of the cells. Experimental evidence clearly shows that
      the blocking of LRP1 function inhibited the PAI-induced migration of resting RAW
      264.7 cells through vitronectin but exerted a pro-migratory effect on CpG-ODN
      activated cells. We also demonstrate that CpG-ODN downregulates the protein and
      mRNA levels of LRP1 both in vivo and in vitro, a function that depends on the NF
      kappaB signaling pathway, resulting in reduced internalization of PAI-1. This
      work illustrates the distinct mechanism that PAI-1-induced migration of CpG-ODN
      activated cells through vitronectin depends on the interaction of PAI-1 with
      vitronectin but not LRP1 unlike in the resting cells, where the migration is LRP1
      dependent and vitronectin independent. In conclusion, our experimental results
      demonstrate the altered function of LRP1 in the migration of resting and
      activated macrophages in the context of microenvironmental extracellular matrix
      components. 

PMID- 24440682
TI  - Distribution, expression and expansion of Aspergillus fumigatus LINE-like
      retrotransposon populations in clinical and environmental isolates.
AB  - Functional genomic analysis of the mould pathogen Aspergillus fumigatus has
      identified multiple secondary metabolism genes upregulated in the host niche.
      Intriguingly, transcriptomic analyses of infectious germlings, germinating spores
      and mutants lacking the LaeA methyltransferase reveal differential expression of
      transposable elements (TEs), which often flank secondary metabolite gene
      clusters. In this study we investigate, in clinical and environmental isolates,
      the structure and distribution of a specific class of A. fumigatus long
      interspersed nuclear element (LINE)-like retrotransposons occupying subtelomeric
      loci in the A. fumigatus genome, and probe their stability in response to
      laboratory- and host-imposed stresses. In silico analyses revealed that this
      class belongs to the Tad clade of LINE-like elements. Southern blotting with a
      LINE-specific probe in clinical and environmental isolates revealed a high
      variability in the insertion pattern between strains and active transcription of
      LINE-like element(s) was discernable, in the type strain Af293, by RT-PCR. One
      out of 14 tested clinical isolates did not contain any LINEs at all, arguing
      against an absolute requirement for LINE-mediated activities in human infections.
      Finally, we found preliminary evidence of an association between mycovirus
      infection and the expansion of Tad-element populations in discrete A. fumigatus
      genomes. 

PMID- 24440683
TI  - Interobserver variability of clinical target volume delineation in soft-tissue
      sarcomas.
AB  - PURPOSE: The present observational study reports the results of a multi
      institutional dummy-run designed to estimate the consistency of interobserver
      variability in clinical target volume delineation in two different cases of soft
      tissue sarcomas in which postoperative and preoperative radiotherapy were
      prescribed, respectively. The purpose of this work was to quantify interobserver
      variability in routine clinical practice. PATIENTS AND METHODS: Two different
      cases of soft-tissues sarcomas were chosen: a case of postoperative and a case of
      preoperative radiation therapy. Participating centres were requested to delineate
      clinical target volumes according to their experience in both cases. Descriptive
      statistic was calculated for each variable (volume, diameters) separately for two
      cases. Box-whiskers plots were used for presentation of clinical target volume. A
      Shapiro-Wilk's test was performed to evaluate the departures from normality
      distribution for each variable. The comparison between relative variations of
      diameters was evaluated using the Student's t test. RESULTS: Several variations
      affecting both volumes and diameters were observed. Main variations were observed
      in the craniocaudal and laterolateral diameters. Each case showed similar
      dispersion, indicating a lack of reproducibility in volumes definition.
      CONCLUSIONS: This observational study highlighted that, in the absence of
      specific instructions or guidelines, the interobserver variability can be
      significant both in postoperative and preoperative radiotherapy of soft-tissue
      sarcomas.

PMID- 24440684
TI  - Multiple tobacco product use among adults in the United States: cigarettes,
      cigars, electronic cigarettes, hookah, smokeless tobacco, and snus.
AB  - OBJECTIVE: Noncigarette tobacco products are increasingly popular. Researchers
      need to understand multiple tobacco product use to assess the effects of these
      products on population health. We estimate national prevalence and examine risk
      factors for multiple product use. METHOD: We calculated prevalence estimates of
      current use patterns involving cigarettes, cigars, electronic cigarettes, hookah,
      smokeless tobacco, and snus using data from the 2012 RTI National Adult Tobacco
      Survey (N=3627), a random-digit-dial telephone survey of adults aged 18 and over.
      Associations between use patterns (exclusive single product and multiple
      products) and demographic characteristics were examined using Pearson chi-square
      tests and logistic regression. RESULTS: 32.1% of adults currently use 1 or more
      tobacco products; 14.9% use cigarettes exclusively, and 6.6% use one noncigarette
      product exclusively, 6.9% use cigarettes with another product (dual use), 1.3%
      use two noncigarette products, and 2.4% use three or more products (polytobacco
      use). Smokers who are young adult, male, never married, reside in the West, and
      made prior quit attempts were at risk for multiple product use. CONCLUSIONS: Over
      10% of U.S. adults use multiple tobacco products. A better understanding of
      multiple product use involving combustible products, like cigars and hookah, is
      needed. Multiple product use may be associated with past quit attempts.

PMID- 24440685
TI  - Trends in age verification among U.S. adolescents attempting to buy cigarettes at
      retail stores, 2000-2009.
AB  - OBJECTIVE: This study assessed trends in age verification prior to cigarette
      sales to U.S. middle and high school students, and refusal to sell cigarettes to
      students aged <18 years during 2000-2009. METHOD: Data were obtained from the
      2000-2009 National Youth Tobacco Survey. Trends during 2000-2009 were assessed
      using binary logistic regression (p<0.05). RESULT: The proportion of all
      students, who reported being asked to show proof of age prior to a cigarette
      purchase in the past 30 days did not change significantly between 2000 (46.9%)
      and 2009 (44.9%) (p=0.529 for linear trend). No significant trend in the
      proportion of students aged < 18 years who were refused a sale when attempting to
      buy cigarettes was observed between 2000 (39.8%) and 2009 (36.7%) (p=0.283 for
      linear trend). Refusal of a cigarette sale was significantly higher among under
      aged boys compared to girls (adjusted odds ratio=1.48; 95% confidence interval:
      1.28-1.70). CONCLUSION: About half of U.S. middle and high school students who
      reported making a cigarette purchase were not asked for proof of age, and about
      three of five under-aged buyers successfully made a cigarette purchase in 2009.
      Intensified implementation and enforcement of policies requiring age verification
      among youths is warranted to reduce access and use of tobacco products.

PMID- 24440686
TI  - Is alcohol mixed with energy drinks consumption associated with susceptibility to
      smoking?
AB  - OBJECTIVE: This paper examines whether adolescent students in Canada who have
      never smoked but who drink alcohol mixed with energy drinks (AmED) are more
      susceptible to smoking than those who do not consume AmED. METHODS: A nationally
      representative sample of 15,875 never-smoking students in grades 9 to 12 from the
      2010-2011 Canadian Youth Smoking Survey is used. The association between AmED and
      susceptibility to smoking is examined using a logistic regression. RESULTS: About
      28% of the never-smoking adolescents in grades 9 to 12 are susceptible to
      smoking, and 13% report using AmED. Results of the adjusted logistic regression
      analysis show a statistically significant positive association between consuming
      AmED and susceptibility to smoking. Never-smoking students who reported using
      AmED are more susceptible to smoking when compared with those who have not
      consumed AmED (OR=1.89; 95% CI=1.71-2.10). Similar results are obtained when the
      analysis is stratified by gender. CONCLUSIONS: The consumption of AmED is
      associated with higher odds of smoking susceptibility among Canadian adolescents.
      AmED use could be a potential marker for smoking susceptibility among never
      smoking adolescents.

PMID- 24440687
TI  - Auditory verbal hallucinations of epileptic origin.
AB  - Complex auditory hallucinations are often characterized by hearing voices and are
      then called auditory verbal hallucinations (AVHs). While AVHs have been
      extensively investigated in psychiatric patients suffering from schizophrenia,
      reports from neurological patients are rare and, in most cases, incomplete. Here,
      we characterize AVHs in 9 patients suffering from pharmacoresistant epilepsy by
      analyzing the phenomenology of AVHs and patients' neuropsychological and lesion
      profiles. From a cohort of 352 consecutively examined patients with epilepsy, 9
      patients suffering AVHs were identified and studied by means of a semistructured
      interview, neuropsychological tests, and multimodal imaging, relying on a
      combination of functional and structural neuroimaging data and surface and
      intracranial EEG. We found that AVHs in patients with epilepsy were associated
      with prevalent language deficits and damage to posterior language areas and basal
      language areas in the left temporal cortex. Auditory verbal hallucinations, most
      of the times, consisted in hearing a single voice of the same gender and language
      as the patient and had specific spatial features, being, most of the times,
      perceived in the external space, contralateral to the lesion. We argue that the
      consistent location of AVHs in the contralesional external space, the prominence
      of associated language deficits, and the prevalence of lesions to the posterior
      temporal language areas characterize AVHs of neurological origin, distinguishing
      them from those of psychiatric origin. 

PMID- 24440688
TI  - Psychometric properties of Chinese language Liverpool Seizure Severity Scale 2.0
      (LSSS 2.0) and status and determinants of seizure severity for patients with
      epilepsy in China.
AB  - OBJECTIVES: This study aimed to translate and validate the Liverpool Seizure
      Severity Scale (LSSS) in Chinese-speaking patients with epilepsy and explore the
      determinants of seizure severity in China. METHODS: Accepted procedures were
      followed to translate the LSSS. Each participant was interviewed to complete the
      LSSS, Seizure Severity Index, Quality of Well-being Scale Self-Administered (QWB
      SA), EuroQol (EQ-5D), and Mini Mental State Examination (MMSE). Construct
      validity and internal consistency were assessed. The determinants of seizure
      severity were explored. RESULTS: The construct validity of the LSSS was
      demonstrated by good convergent and discriminant validities. Cronbach's alpha and
      the intraclass correlation coefficient were 0.886, respectively. In the
      multivariate analysis, seizure types (p=0.001), seizure frequency (p=0.001), and
      numbers of antiepileptic drugs (p=0.042) predicted the scores on the LSSS. Types
      of antiepileptic drugs also contributed to the variation in the LSSS scores.
      CONCLUSIONS: Chinese LSSS is a valid, reliable, and sensitive seizure severity
      scale. Seizure frequency, seizure types, and quantities and types of AEDs predict
      seizure severity.

PMID- 24440689
TI  - Alternative medicine as a coping strategy for people with epilepsy: can exercise
      of religion and spirituality be part of this context?

PMID- 24440690
TI  - Contribution of dopaminergic and adenosinergic systems in the antinociceptive
      effect of p-chloro-selenosteroid.
AB  - This study investigated the antinociceptive action of p-chloro-selenosteroid
      (PCS), administered by intragastric route (i.g.) to mice against acute models.
      The contribution of adenosinergic, dopaminergic, serotonergic, nitric oxide and
      opioid systems was investigated. It was evaluated if the administration of PCS
      triggers toxic effect. Treatment with PCS (10mg/kg) reduced writhing induced by
      acetic acid and its effect lasts up to 48 h after treatment. The compound caused
      an inhibition in neurogenic and inflammatory phases of nociception and in paw
      edema induced by formalin. The licking behavior triggered by glutamate was
      reduced by PCS. In the tail-immersion test, PCS elicited an increase in delta
      latency response. Pretreatment with caffeine (3mg/kg, intraperitoneally [i.p.])
      and SCH58261 (3mg/kg, i.p.), antagonist at adenosinergic receptors, SCH23390
      (0.05 mg/kg, i.p.) and sulpiride (5mg/kg, i.p.), antagonist at dopaminergic
      receptors, caused a reduction in the antinociceptive action of PCS in the
      glutamate test. By contrast, pretreatment with WAY100635 (0.7 mg/kg, i.p.),
      ketanserin (0.3mg/kg, i.p.), ondasentron (0.5mg/kg, i.p.), l-arginine (600 mg/kg,
      i.p.) and naloxone (1mg/kg, subcutaneous [s.c.]) did not abolish the
      antinociceptive effect caused by PCS (10mg/kg, i.g.) administration. The animals
      treated with PCS did not show alterations in locomotor and exploratory
      activities, in biochemical parameters evaluated, food and water consumption, as
      well as in the body weight. These results clearly showed the antinociceptive
      action of PCS in different animal models without causing acute toxic effects in
      mice. Adenosinergic and dopaminergic systems seem to be related to the mechanisms
      by which PCS elicits antinociception.

PMID- 24440691
TI  - Involvement of transient receptor potential melastatin-8 (TRPM8) in menthol
      induced calcium entry, reactive oxygen species production and cell death in
      rheumatoid arthritis rat synovial fibroblasts.
AB  - Rheumatoid arthritis is most prominently characterized by synoviocyte hyperplasia
      which therefore serves as an important target for clinical therapy. In the
      present study, it was observed that menthol, the specific agonist of transient
      receptor potential melastatin subtype 8 (TRPM8), could induce sustained increases
      of cytosolic calcium concentration ([Ca(2+)]c) in synoviocytes isolated from
      collagen-induced arthritis rats in dose-dependent manner, which was evidently
      blocked by applying an extracellular Ca(2+)-free buffer. Menthol-induced
      [Ca(2+)]c increase was also significantly inhibited by potent TRPM8 antagonist
      capsazepine (CZP), indicating that this [Ca(2+)]c elevation was mostly attributed
      to TRPM8-mediated Ca(2+) entry. Besides, RT-PCR indeed demonstrated presence of
      TRPM8 in the synoviocytes. Meanwhile, it was found that menthol evoked production
      of intracellular reactive oxygen species, which could be abolished by Ca(2+) free
      solutions or CZP. Further experiments showed that menthol reduced the cell
      numbers and survival of synoviocytes. This reduction was associated with
      apoptosis as suggested by mitochondrial membrane depolarization, nuclear
      condensation and a caspase 3/7 apoptotic assay. Menthol-induced death and
      apoptosis of synoviocytes both were obviously inhibited by CZP, intracellular
      calcium chelator BAPTA-AM, and reactive oxygen species inhibitor diphenylene
      iodonium, respectively. Taken together, our data indicated that menthol resulted
      in synoviocyte death associated with apoptosis via calcium entry and reactive
      oxygen species production depending on TRPM8 activation. 

PMID- 24440692
TI  - Leaching of plastic additives to marine organisms.
AB  - It is often assumed that ingestion of microplastics by aquatic species leads to
      increased exposure to plastic additives. However, experimental data or model
      based evidence is lacking. Here we assess the potential of leaching of
      nonylphenol (NP) and bisphenol A (BPA) in the intestinal tracts of Arenicola
      marina (lugworm) and Gadus morhua (North Sea cod). We use a biodynamic model that
      allows calculations of the relative contribution of plastic ingestion to total
      exposure of aquatic species to chemicals residing in the ingested plastic.
      Uncertainty in the most crucial parameters is accounted for by probabilistic
      modeling. Our conservative analysis shows that plastic ingestion by the lugworm
      yields NP and BPA concentrations that stay below the lower ends of global NP and
      BPA concentration ranges, and therefore are not likely to constitute a relevant
      exposure pathway. For cod, plastic ingestion appears to be a negligible pathway
      for exposure to NP and BPA. 

PMID- 24440693
TI  - Commentary to "a novel alternative for renal replacement therapy for developing
      countries: two-year successful colonic dialysis via Malone antegrade continent
      enema stoma".

PMID- 24440694
TI  - Desferrioxamine effectively attenuates testicular tissue at the end of 3 h of
      ischemia but not in an equal period of reperfusion.
AB  - OBJECTIVE: To investigate the effect of desferrioxamine (DFX) on ipsilateral and
      contralateral testis damage caused by experimental testis torsion and detorsion.
      MATERIALS AND METHODS: Forty rats were divided into five groups (n = 8): control,
      torsion (T), torsion + desferrioxamine (T + DFX), torsion/detorsion (T/D), and
      torsion/detorsion + desferrioxamine (T/D + DFX). The right testes of the rats
      were subjected to torsion and detorsion for 3 h each. Thirty minutes before the
      application of torsion and detorsion, DFX (100 mg/kg) was administered
      intramuscularly. Blood samples and testicular tissues were examined using
      specific biochemical and histopathological methods. RESULTS: Ipsilateral and
      contralateral testis tissue glutathione levels in the T group decreased compared
      with the control and T + DFX groups. Plasma glutathione peroxidase activity in
      the T, T/D, and T/D + DFX groups was lower than in the control group. Plasma
      catalase activity in the T and T/D groups decreased compared with the control
      group. Ipsilateral mean seminiferous tubule diameter of the T group was lower
      than that of the T + DFX group. The ipsilateral mean testis biopsy scores in the
      T and T/D groups were lower than in the control group. CONCLUSION: The
      administration of DFX prior to torsion may be useful only for preventing ischemic
      damage in ipsilateral and contralateral testes.

PMID- 24440695
TI  - Surgical technique: Retroperitoneoscopic approach for adrenal masses in children.
AB  - Laparoscopic adrenalectomy is considered to be the standard of care for the
      surgical excision of adrenal masses. The transperitoneal laparoscopic and
      retroperitoneoscopic approaches are described. Both are safe and as effective as
      open adrenalectomy, with the added benefit of the minimally invasive approach. It
      can be utilized for patients requiring surgery for a phaeochromocytoma, adrenal
      adenoma, adrenal adenocarcinoma, Cushing's syndrome, neuroblastoma, and an
      incidentaloma. Relative contraindications include previous surgery of the liver
      or kidney, large tumours (>8-10 cm in diameter) or coagulation disorders.
      Although the transperitoneal route is used more widely, the retroperitoneal
      approach provides direct access to the adrenal gland and easy visualization of
      the adrenal vein. It avoids also colonic mobilization, minimizes the risk of
      injury to hollow viscera, and the potential risk of adhesion formation. However,
      the reversed orientation of the kidney and hilum, combined with a significantly
      smaller working space, may make this approach difficult to master.

PMID- 24440696
TI  - Developmental genetic profiles of glutamate receptor system, neuromodulator
      system, protector of normal tissue and mitochondria, and reelin in marmoset
      cortex: potential molecular mechanisms of pruning phase of spines in primate
      synaptic formation process during the end of infancy and prepuberty (II).
AB  - This is the second report of a series paper, which reports molecular mechanisms
      underlying the occurrence of pruning spine phase after rapid spinogenesis phase
      in neonates and young infant in the primate brain. We performed microarray
      analysis between the peak of spine numbers [postnatal 3 months (M)] and spine
      pruning (postnatal 6M) in prefrontal, inferior temporal, and primary visual
      cortices of the common marmoset (Callithrix jacchus). The pruning phase is not
      clearly defined in rodents but is in primates including the marmoset. The
      differentially expressed genes between 3M and 6M in all three cortical areas were
      selected by two-way analysis of variance. The list of selected genes was analyzed
      by canonical pathway analysis using "Ingenuity Pathway Analysis of complex omics
      data" (IPA; Ingenuity Systems, Qiagen, Hilden, Germany). In this report, we
      discuss these lists of genes for the glutamate receptor system, G-protein-coupled
      neuromodulator system, protector of normal tissue and mitochondria, and reelin.
      (1) Glutamate is a common neurotransmitter. Its receptors AMPA1, GRIK1, and their
      scaffold protein DLG4 decreased as spine numbers decreased. Instead, GRIN3 (NMDA
      receptor) increased, suggesting that strong NMDA excitatory currents may be
      required for a single neuron to receive sufficient net synaptic activity in order
      to compensate for the decrease in synapse. (2) Most of the G protein-coupled
      receptor genes (e.g., ADRA1D, HTR2A, HTR4, and DRD1) in the selected list were
      upregulated at 6M. The downstream gene ROCK2 in these receptor systems plays a
      role of decreasing synapses, and ROCK2 decreased at 6M. (3) Synaptic phagosytosis
      by microglia with complement and other cytokines could cause damage to normal
      tissue and mitochondria. SOD1, XIAP, CD46, and CD55, which play protective roles
      in normal tissue and mitochondria, showed higher expression at 6M than at 3M,
      suggesting that normal brain tissue is more protected at 6M. (4) Reelin has an
      important role in cortical layer formation. In addition, RELN and three different
      pathways of reelin were expressed at 6M, suggesting that new synapse formation
      decreased at that age. Moreover, if new synapses were formed, their positions
      were free and probably dependent on activity.

PMID- 24440697
TI  - Elasto-regenerative properties of polyphenols.
AB  - Abdominal aortic aneurysms (AAA) are progressive dilatations of infra-renal aorta
      causing structural weakening rendering the aorta prone to rupture. AAA can be
      potentially stabilized by inhibiting inflammatory enzymes such as matrix
      metalloproteinases (MMP); however, active regression of AAA is not possible
      without new elastic fiber regeneration. Here we report the elastogenic benefit of
      direct delivery of polyphenols such as pentagalloyl glucose (PGG),
      epigallocatechin gallate (EGCG), and catechin, to smooth muscle cells obtained
      either from healthy or from aneurysmal rat aorta. Addition of 10 MUg/ml PGG and
      ECGC induce elastin synthesis, organization, and crosslinking while catechin does
      not. Our results indicate that polyphenols bind to monomeric tropoelastin and
      enhance coacervation, aid in crosslinking of elastin by increasing lysyl oxidase
      (LOX) synthesis, and by blocking MMP-2 activity. Thus, polyphenol treatments
      leads to increased mature elastin fibers synthesis without increasing the
      production of intracellular tropoelastin.

PMID- 24440698
TI  - Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons.
AB  - Wnt signaling has a crucial role in synaptic function at the central nervous
      system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in
      hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production;
      however, Wnt-3a a canonical ligand did not exert the same effect. Co
      administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a
      Wnt antagonist blocked the NO production. Wnt-5a activates the non-canonical
      Wnt/Ca(2+) signaling through a mechanism that depends on Ca(2+) release from
      Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a
      promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into
      the neuronal cell surface. To the best of our knowledge, this is the first time
      that Wnt-5a signaling is related to NO production, which in turn increases NMDARs
      trafficking to the cell surface. 

PMID- 24440699
TI  - Effect of amino acid variations in the central region of human serum amyloid A on
      the amyloidogenic properties.
AB  - Human serum amyloid A (SAA) is a precursor protein of the amyloid fibrils that
      are responsible for AA amyloidosis. Of the four human SAA genotypes, SAA1 is most
      commonly associated with AA amyloidosis. Furthermore, SAA1 has three major
      isoforms (SAA1.1, 1.3, and 1.5) that differ by single amino acid variations at
      two sites in their 104-amino acid sequences. In the present study, we examined
      the effect of amino acid variations in human SAA1 isoforms on the amyloidogenic
      properties. All SAA1 isoforms adopted alpha-helix structures at 4 degrees C, but
      were unstructured at 37 degrees C. Heparin-induced amyloid fibril formation of
      SAA1 was observed at 37 degrees C, as evidenced by the increased thioflavin T
      (ThT) fluorescence and beta-sheet structure formation. Despite a comparable
      increase in ThT fluorescence, SAA1 molecules retained their alpha-helix
      structures at 4 degrees C. At both temperatures, no essential differences in ThT
      fluorescence and secondary structures were observed among the SAA1 isoforms.
      However, the fibril morphologies appeared to differ; SAA1.1 formed long and curly
      fibrils, whereas SAA1.3 formed thin and straight fibrils. The peptides
      corresponding to the central regions of the SAA1 isoforms containing amino acid
      variations showed distinct amyloidogenicities, reflecting their direct effects on
      amyloid fibril formation. These findings may provide novel insights into the
      influence of amino acid variations in human SAA on the pathogenesis of AA
      amyloidosis. 

PMID- 24440700
TI  - Identification and expression profile analysis of putative odorant-binding
      proteins in Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae).
AB  - Odorant binding proteins (OBPs) contribute to the remarkable sensitivity of the
      insect's olfactory system and play important roles in the olfactory recognition.
      The orange blossom midge, Sitodiplosis mosellana is a cereal specialist, and
      utilizes pheromone and host odorant as a cue for its mating and oviposition.
      However, OBP genes have not been largely identified in S. mosellana. Based on the
      sequenced transcriptome database, twenty-six OBP genes were identified in S.
      mosellana for the first time. Phylogenetic analysis revealed that S. mosellana
      OBP genes are more closely related to Mayetiola destructor OBP genes than to
      Aedes aegypti OBP genes. Most OBP genes seemed to be antenna-specific, but
      differentially expressed in male and female antennae. Three OBP genes (OBP9,
      OBP19 and OBP23) are leg-specific. And also, most OBP genes have higher
      expression levels in adults. Only one OBP gene (OBP10) has higher expression
      levels in larval stages. These findings serve as an important basis for
      understanding the molecular mechanisms of chemosensory perception. 

PMID- 24440701
TI  - MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA.
AB  - Colorectal cancer (CRC) is the second most common cause of death from cancer.
      MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene
      expression by triggering RNA degradation or interfering with translation.
      Aberrant miRNA expression is involved in human disease including cancer. Herein,
      we showed that miR-375 was frequently down-regulated in human colorectal cancer
      cell lines and tissues when compared to normal human colon tissues. PIK3CA was
      identified as a potential miR-375 target by bioinformatics. Overexpression of miR
      375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently,
      using reporter constructs, we showed that the PIK3CA untranslated region (3'-UTR)
      carries the directly binding site of miR-375. Additionally, miR-375 suppressed
      CRC cell proliferation and colony formation and led to cell cycle arrest.
      Furthermore, miR-375 overexpression resulted in inhibition of
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated
      silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth.
      Lastly, we found overexpressed miR-375 effectively repressed tumor growth in
      xenograft animal experiments. Taken together, we propose that overexpression of
      miR-375 may provide a selective growth inhibition for CRC cells by targeting
      PI3K/Akt signaling pathway. 

PMID- 24440702
TI  - Phylogenetic comparison of oskar mRNA localization signals.
AB  - As a way to spatially control the expression of genes within cells, RNA
      localization is being recognized as an important process by which proteins are
      restricted to specific subcellular domains, which occurs in more diverse types of
      tissue than previously considered. Although many localized RNAs have been
      identified, information on cis-acting elements of localization is still limited.
      As transcripts of oskar (osk) are known to localize to the posterior pole of
      oocytes, we computationally analyzed a conserved sequence among eight Drosophila
      species and tested its role as a localization element. Dimerization of osk mRNA
      did not occur when the motif was deleted, but this did not affect assembly of osk
      mRNA-containing ribonucleoprotein (RNP) complexes. Without the motif, however,
      large RNP complex particles accumulated in nurse cells, and only a small fraction
      of these RNP complexes was transported into oocytes and properly localized to the
      posterior pole. Therefore, this motif may be required for the early transport of
      osk mRNA into oocytes. Also, as dimerization of osk mRNA does not seem to be a
      prerequisite for the assembly of RNP complexes, a dimerization-independent
      mechanism may also serve to localize osk mRNA to the posterior pole. 

PMID- 24440703
TI  - Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in
      experimental ischemic stroke.
AB  - Rapamycin has been demonstrated to exhibit neuroprotective functions via the
      activation of autophagy in a cerebral ischemia model. However, the involvement of
      mitophagy in this process and its contribution to the protection of mitochondrial
      function remains unknown. The present study explored the characteristics of
      mitophagy after cerebral ischemia and the effect of rapamycin on mitochondrial
      function. Male Sprague-Dawley rats underwent transient middle cerebral artery
      occlusion (tMCAO). Neurological deficits scores; infarct volumes; mitophagy
      morphology; and the levels of malondialdehyde (MDA), adenosine triphosphate (ATP)
      and mitochondrial membrane potentials (Deltapsim) were examined. The expression
      of LC3, Beclin-1 and p62 in the mitochondrial fraction combined with transmission
      electronic microscopy were used to explore mitophagic activity after ischemia. We
      also blocked autophagosome formation using 3-methyladenine (3-MA) to check the
      linkage between the mitochondrial protective effect of rapamycin and enhanced
      mitophagy. We observed that rapamycin significantly enhanced mitophagy, as
      evidenced by the increase in LC3-II and Beclin-1 expression in the mitochondria
      and p62 translocation to the mitochondria. Rapamycin reduced infarct volume,
      improved neurological outcomes and inhibited mitochondrial dysfunction compared
      with the control animals (p<0.05). However, these protective effects were
      reversed by 3-methyladenine treatment after rapamycin. The present study
      indicates that rapamycin treatment attenuates mitochondrial dysfunction following
      cerebral ischemia, which is linked to enhanced mitophagy. 

PMID- 24440704
TI  - Astrocytic gap junctional networks suppress cellular damage in an in vitro model
      of ischemia.
AB  - Astrocytes play pivotal roles in both the physiology and the pathophysiology of
      the brain. They communicate with each other via extracellular messengers as well
      as through gap junctions, which may exacerbate or protect against pathological
      processes in the brain. However, their roles during the acute phase of ischemia
      and the underlying cellular mechanisms remain largely unknown. To address this
      issue, we imaged changes in the intracellular calcium concentration ([Ca(2+)]i)
      in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD)
      condition using two-photon microscopy. Under OGD, astrocytes showed [Ca(2+)]i
      oscillations followed by larger and sustained [Ca(2+)]i increases. While the
      pharmacological blockades of astrocytic receptors for glutamate and ATP had no
      effect, the inhibitions of gap junctional intercellular coupling between
      astrocytes significantly advanced the onset of the sustained [Ca(2+)]i increase
      after OGD exposure. Interestingly, the simultaneous recording of the neuronal
      membrane potential revealed that the onset of the sustained [Ca(2+)]i increase in
      astrocytes was synchronized with the appearance of neuronal anoxic
      depolarization. Furthermore, the blockade of gap junctional coupling resulted in
      a concurrent faster appearance of neuronal depolarizations, which remain
      synchronized with the sustained [Ca(2+)]i increase in astrocytes. These results
      indicate that astrocytes delay the appearance of the pathological responses of
      astrocytes and neurons through their gap junction-mediated intercellular network
      under OGD. Thus, astrocytic gap junctional networks provide protection against
      tissue damage during the acute phase of ischemia. 

PMID- 24440705
TI  - MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting
      CCND1.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the
      translation of messenger RNAs by binding their 3'-untranslated region (3'UTR). In
      this study, we found that miR-490-3p is significantly down-regulated in A549 lung
      cancer cells compared with the normal bronchial epithelial cell line. To better
      characterize the role of miR-490-3p in A549 cells, we performed a gain-of
      function analysis by transfecting the A549 cells with chemically synthesized miR
      490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation
      via G1-phase arrest. We also found that forced expression of miR-490-3P decreased
      both mRNA and protein levels of CCND1, which plays a key role in G1/S phase
      transition. In addition, the dual-luciferase reporter assays indicated that miR
      490-3P directly targets CCND1 through binding its 3'UTR. These findings indicated
      miR-490-3P could be a potential suppressor of cellular proliferation. 

PMID- 24440707
TI  - Regulation of miRNA during direct reprogramming of dental pulp cells to insulin
      producing cells.
AB  - To further evaluate the multipotency of dental pulp cells, and to investigate the
      possible direct reprogramming of these cells, we examined their in vitro
      induction of direct conversion to an endocrine cell lineage. In vitro induction
      was carried out using similar conditions to those reported for regulating the
      differentiation of undifferentiated intestinal cells into endocrine progenitor
      cells. Specifically, the transcription factors Pdx1 and Neurog3 were transfected
      into rat dental pulp cells to induce their direct conversion to endocrine lineage
      cells. The degree of induction was evaluated by detecting insulin-producing
      cells. Using a miRCURY LNA microRNA Array (Exiqon), the miRNA expression profiles
      were comprehensively analyzed. At 10 days after induction, insulin-producing
      cells were detected. Based on the expression profiles, eight miRNA probes showing
      significant differences at 10 days after induction compared with their pre
      induction baseline values were extracted after filtering. Notably, miR-183 was
      downregulated by less than 40% after induction. Following a target scan of miR
      183, we identified 242 conserved targets, including molecules crucial for the
      development of pancreatic beta-cells such as Foxo1. These findings indicate that
      dental pulp cells have potential for direct reprogramming to insulin-producing
      cells. This potential ability for direct reprogramming of dental pulp cells shows
      promise for clinically relevant tissue engineering materials.

PMID- 24440706
TI  - Thyroid hormone status regulates the expression of secretory phospholipases.
AB  - Thyroid hormone (T3) stimulates various metabolic pathways and the hepatic
      actions of T3 are mediated primarily through the thyroid hormone receptor beta
      (TRbeta). Hypothyroidism has been linked with low grade inflammation, elevated
      risk of hepatic steatosis and atherosclerosis. Secretory phospholipases (sPLA2)
      are associated with inflammation, hyperlipidemia and atherosclerosis. Due to
      potential linkage between thyroid hormone and sPLA2, we investigated the effect
      of thyroid hormone status on the regulation of secretory phospholipases in mice,
      rats and human liver. T3 suppressed the expression of the sPLA2 group IIa
      (PLA2g2a) gene in the liver of BALB/c mice and C57BL/6 transgenic mice expressing
      the human PLA2g2a. PLA2g2a was elevated with hypothyroidism and high fat diets
      which may contribute to the low grade inflammation associated with hypothyroidism
      and diet induced obesity. We also examined the effects of the TRbeta agonist
      eprotirome on hepatic gene regulation. We observed that eprotirome inhibited the
      expression of selected sPLA2 genes and furthermore the cytokine mediated
      induction PLA2g2a was suppressed. In addition, eprotirome induced genes involved
      in fatty acid oxidation and cholesterol clearance while inhibiting lipogenic
      genes. Our results indicate that in vivo thyroid hormone status regulates the
      abundance of sPLA2 and the inhibition of PLA2g2a by T3 is conserved across
      species. By regulating sPLA2 genes, T3 may impact processes associated with
      atherosclerosis and inflammation and TRbeta agonists may ameliorate inflammation
      and hyperlipidemia. 

PMID- 24440708
TI  - Translating in vitro prediction of cytotoxic T cell alloreactivity to
      hematopoietic stem cell transplantation outcome.
AB  - INTRODUCTION: Previously we developed a weighted amino acid (AA) mismatch score
      predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based
      on the structure of the HLA class I molecule. The aim of this study is to confirm
      the clinical relevance of the CTLp assay and to validate the AA mismatch score as
      an alternative and easy to use tool to predict permissible mismatches in
      hematopoietic stem cell transplantation (HSCT). METHODS: We selected patients
      transplanted with a 9/10 single HLA class I mismatched graft (n=171) at three
      Dutch HSCT centers. A CTLp assay was performed in 73 donor-recipient pairs. As a
      control we selected 168 10/10 HLA matched pairs that were matched to the 9/10
      single HLA class I mismatched pairs for HSCT year, donor type, patient age and
      diagnosis. RESULTS: We observed that pairs with negative a CTLp assay had
      statistically significant decreased incidence of mortality after HSCT comparable
      to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did
      not significantly predict any HSCT end point of interest. CONCLUSION: Further
      investigation is needed to unravel the mechanisms involved in causing the
      beneficial effect of a negative CTLp assay, before other alternative tools to
      predict HSCT outcome may be developed.

PMID- 24440709
TI  - Survivin and YM155: how faithful is the liaison?
AB  - Survivin belongs to the family of apoptosis inhibitors (IAPs), which antagonizes
      the induction of cell death. Dysregulated expression of IAPs is frequently
      observed in cancers, and the high levels of survivin in tumors compared to normal
      adult tissues make it an attractive target for pharmacological interventions. The
      small imidazolium-based compound YM155 has recently been reported to block the
      expression of survivin via inhibition of the survivin promoter. Recent data,
      however, question that this is the sole and main effect of this drug, which is
      already being tested in ongoing clinical studies. Here, we critically review the
      current data on YM155 and other new experimental agents supposed to antagonize
      survivin. We summarize how cells from various tumor entities and with
      differential expression of the tumor suppressor p53 respond to this agent in
      vitro and as murine xenografts. Additionally, we recapitulate clinical trials
      conducted with YM155. Our article further considers the potency of YM155 in
      combination with other anti-cancer agents and epigenetic modulators. We also
      assess state-of-the-art data on the sometimes very promiscuous molecular
      mechanisms affected by YM155 in cancer cells. 

PMID- 24440710
TI  - Metabolism and functions of copper in brain.
AB  - Copper is an important trace element that is required for essential enzymes.
      However, due to its redox activity, copper can also lead to the generation of
      toxic reactive oxygen species. Therefore, cellular uptake, storage as well as
      export of copper have to be tightly regulated in order to guarantee sufficient
      copper supply for the synthesis of copper-containing enzymes but also to prevent
      copper-induced oxidative stress. In brain, copper is of importance for normal
      development. In addition, both copper deficiency as well as excess of copper can
      seriously affect brain functions. Therefore, this organ possesses ample
      mechanisms to regulate its copper metabolism. In brain, astrocytes are considered
      as important regulators of copper homeostasis. Impairments of homeostatic
      mechanisms in brain copper metabolism have been associated with neurodegeneration
      in human disorders such as Menkes disease, Wilson's disease and Alzheimer's
      disease. This review article will summarize the biological functions of copper in
      the brain and will describe the current knowledge on the mechanisms involved in
      copper transport, storage and export of brain cells. The role of copper in
      diseases that have been connected with disturbances in brain copper homeostasis
      will also be discussed. 

PMID- 24440711
TI  - How is research publishing going to progress in the next 20 years?: transcription
      of session for editors, associate editors, publishers and others with an interest
      in scientific publishing held at IADR meeting in Seattle on Wednesday, 20 March
      2013.
AB  - On March 20th 2013, a one-hour session for Editors, Associate Editors, Publishers
      and others with an interest in scientific publishing was held at the IADR
      International Session in Seattle. Organised by Kenneth Eaton and Christopher
      Lynch (Chair and Secretary, respectively, of the British Dental Editors Forum),
      the meeting sought to bring together leading international experts in dental
      publishing, as well as authors, reviewers and students engaged in research. The
      meeting was an overwhelming success, with more than 100 attendees. A panel
      involving four leading dental editors led a discussion on anticipated
      developments in publishing dental research with much involvement and contribution
      from audience members. This was the third such meeting held at the IADR for
      Editors, Associate Editors, Publishers and others with an interest in scientific
      publishing. A follow-up session will take place in Cape Town on 25 June 2014 as
      part of the annual IADR meeting. The transcript of the Seattle meeting is
      reproduced in this article. Where possible speakers are identified by name. At
      the first time of mention their role/position is also stated, thereafter only
      their name appears. We are grateful to Stephen Hancocks Ltd. for their generous
      sponsorship of this event. For those who were not able to attend the authors hope
      this article gives a flavour of the discussions and will encourage colleagues to
      attend future events. Involvement is open to Editors, Associate Editors,
      Publishers and others with an interest in scientific publishing. It is a very
      open group and all those with an interest will be welcome to join in.

PMID- 24440712
TI  - Combined effect of a fluoride-, stannous- and chitosan-containing toothpaste and
      stannous-containing rinse on the prevention of initial enamel erosion-abrasion.
AB  - OBJECTIVES: The aim of this study was to assess the preventive effect of a
      fluoride-, stannous- and chitosan-containing (F/Sn/chitosan-) toothpaste (TP) on
      initial enamel erosion and abrasion. METHODS: In total, 150 human premolar enamel
      specimens were ground, polished and divided into 5 toothpaste/rinse groups
      (n=30): (G1) placebo-TP/tap water, (G2) sodium fluoride (NaF-) TP/tap water, (G3)
      F/Sn/chitosan-TP/tap water, (G4) F/Sn/chitosan-TP/Sn-rinse, (G5) NaF-TP/NaF
      rinse. The 8-day erosion-abrasion cyclic treatment (one cycle/day) consisted of
      incubating the samples in artificial saliva (30min), then submitting the samples
      to toothbrush abrasion (2min incubation in toothpaste slurry; brushing with 20
      toothbrush strokes) and rinsing (2min; 10ml) with the respective solution: tap
      water (G1-G3), Sn-rinse (G4) or NaF-rinse (G5). Afterwards, the samples were
      submitted to erosion (2min; 30ml 1% citric acid, pH=3.6). Surface microhardness
      (SMH) was measured initially and after every abrasion and erosion treatment.
      Enamel substance loss was calculated after each abrasion. Non-parametric ANOVA
      followed by Wilcoxon rank tests were used for analysis. RESULTS: G1 presented the
      greatest SMH decrease, while G4 presented the least SMH decrease (p<0.001). G3
      had a similar SMH decrease to G2 and G5. Substance loss was significantly lower
      in G4 than all other groups (p<0.05), closely followed by G3. Both G2 and G5
      showed similar calculated enamel substance loss to G1. CONCLUSION: The treatment
      with F/Sn/chitosan-TP and tap water provided a similar SMH decrease to both NaF
      TP groups, but significantly lower substance loss. F/Sn/Chitosan-TP and Sn-rinse
      showed a better preventive effect, which promoted less SMH decrease and reduced
      substance loss. CLINICAL SIGNIFICANCE: The toothpaste containing fluoride,
      stannous and chitosan shows promising results in reducing substance loss from
      erosion and abrasion. The combination of this toothpaste with the stannous
      containing rinse showed even better prevention against erosion-abrasion.

PMID- 24440713
TI  - Modeling inoculum dose dependent patterns of acute virus infections.
AB  - Inoculum dose, i.e. the number of pathogens at the beginning of an infection,
      often affects key aspects of pathogen and immune response dynamics. These in turn
      determine clinically relevant outcomes, such as morbidity and mortality. Despite
      the general recognition that inoculum dose is an important component of infection
      outcomes, we currently do not understand its impact in much detail. This study is
      intended to start filling this knowledge gap by analyzing inoculum dependent
      patterns of viral load dynamics in acute infections. Using experimental data for
      adenovirus and infectious bronchitis virus infections as examples, we demonstrate
      inoculum dose dependent patterns of virus dynamics. We analyze the data with the
      help of mathematical models to investigate what mechanisms can reproduce the
      patterns observed in experimental data. We find that models including components
      of both the innate and adaptive immune response are needed to reproduce the
      patterns found in the data. We further analyze which types of innate or adaptive
      immune response models agree with observed data. One interesting finding is that
      only models for the adaptive immune response that contain growth terms partially
      independent of viral load can properly reproduce observed patterns. This agrees
      with the idea that an antigen-independent, programmed response is part of the
      adaptive response. Our analysis provides useful insights into the types of model
      structures that are required to properly reproduce observed virus dynamics for
      varying inoculum doses. We suggest that such models should be taken as basis for
      future models of acute viral infections. 

PMID- 24440714
TI  - Metabolic engineering of Escherichia coli for production of fatty acid short
      chain esters through combination of the fatty acid and 2-keto acid pathways.
AB  - Fatty acid short-chain esters (FASEs) are biodiesels that are renewable,
      nontoxic, and biodegradable biofuels. A novel approach for the biosynthesis of
      FASEs has been developed using metabolically-engineered E. coli through
      combination of the fatty acid and 2-keto acid pathways. Several genetic
      engineering strategies were also developed to increase fatty acyl-CoA
      availability to improve FASEs production. Fed-batch cultivation of the engineered
      E. coli resulted in a titer of 1008 mg/L FASEs. Since the fatty acid and 2-keto
      acid pathways are native microbial synthesis pathways, this strategy can be
      implemented in a variety of microorganisms to produce various FASEs from cheap
      and readily-available, renewable, raw materials such as sugars and cellulose in
      the future.

PMID- 24440716
TI  - miR-342-5p decreases ankyrin G levels in Alzheimer's disease transgenic mouse
      models.
AB  - MicroRNA alterations and axonopathy have been reported in patients with
      Alzheimer's disease (AD) and in AD mouse models. We now report that miR-342-5p is
      upregulated in APP/PS1, PS1DeltaE9, and PS1-M146V transgenic AD mice, and that
      this upregulation is mechanistically linked to elevated beta-catenin, c-Myc, and
      interferon regulatory factor-9. The increased miR-342-5p downregulates the
      expression of ankyrin G (AnkG), a protein that is known to play a critical role
      at the axon initial segment. Thus, a specific miRNA alteration may contribute to
      AD axonopathy by downregulating AnkG. 

PMID- 24440715
TI  - Pain without nociceptors? Nav1.7-independent pain mechanisms.
AB  - Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain
      and olfaction in mice and humans. We examined the role of Nav1.7 as well as
      Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain.
      Constriction-injury-dependent neuropathic pain is abolished when Nav1.7 is
      deleted in sensory neurons, unlike nerve-transection-related pain, which requires
      the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief.
      Sympathetic sprouting that develops in parallel with nerve-transection pain
      depends on the presence of Nav1.7 in sympathetic neurons. Mechanical and cold
      allodynia required distinct sets of neurons and different repertoires of sodium
      channels depending on the nerve injury model. Surprisingly, pain induced by the
      chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require
      the presence of Nav1.7 sodium channels or Nav1.8-positive nociceptors. Thus,
      similar pain phenotypes arise through distinct cellular and molecular mechanisms.
      Therefore, rational analgesic drug therapy requires patient stratification in
      terms of mechanisms and not just phenotype.

PMID- 24440717
TI  - Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors.
AB  - Despite a wealth of preclinical studies, it is unclear whether PIK3CA or
      phosphatase and tensin homolog (PTEN) gene aberrations are actionable in the
      clinical setting. Of 1,656 patients with advanced, refractory cancers tested for
      PIK3CA or PTEN abnormalities, PIK3CA mutations were found in 9% (146/1,589), and
      PTEN loss and/or mutation was found in 13% (149/1,157). In multicovariable
      analysis, treatment with a phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian
      target of rapamycin (mTOR) inhibitor was the only independent factor predicting
      response to therapy in individuals harboring a PIK3CA or PTEN aberration. The
      rate of stable disease >=6 months/partial response reached 45% in a subgroup of
      individuals with H1047R PIK3CA mutations. Aberrations in the PI3K/AKT/mTOR
      pathway are common and potentially actionable in patients with diverse advanced
      cancers. This work provides further important clinical validation for continued
      and accelerated use of biomarker-driven trials incorporating rational drug
      combinations.

PMID- 24440719
TI  - The earliest transcribed zygotic genes are short, newly evolved, and different
      across species.
AB  - The transition from maternal to zygotic control is fundamental to the life cycle
      of all multicellular organisms. It is widely believed that genomes are
      transcriptionally inactive from fertilization until zygotic genome activation
      (ZGA). Thus, the earliest genes expressed probably support the rapid cell
      divisions that precede morphogenesis and, if so, might be evolutionarily
      conserved. Here, we identify the earliest zygotic transcripts in the zebrafish,
      Danio rerio, through metabolic labeling and purification of RNA from staged
      embryos. Surprisingly, the mitochondrial genome was highly active from the one
      cell stage onwards, showing that significant transcriptional activity exists at
      fertilization. We show that 592 nuclear genes become active when cell cycles are
      still only 15 min long, confining expression to relatively short genes.
      Furthermore, these zygotic genes are evolutionarily younger than those expressed
      at other developmental stages. Comparison of fish, fly, and mouse data revealed
      different sets of genes expressed at ZGA. This species specificity uncovers an
      evolutionary plasticity in early embryogenesis that probably confers substantial
      adaptive potential.

PMID- 24440718
TI  - Regulation of chandelier cell cartridge and bouton development via DOCK7-mediated
      ErbB4 activation.
AB  - Chandelier cells (ChCs), typified by their unique axonal morphology, are the most
      distinct interneurons present in cortical circuits. Via their distinctive axonal
      terminals, called cartridges, these cells selectively target the axon initial
      segment of pyramidal cells and control action potential initiation; however, the
      mechanisms that govern the characteristic ChC axonal structure have remained
      elusive. Here, by employing an in utero electroporation-based method that enables
      genetic labeling and manipulation of ChCs in vivo, we identify DOCK7, a member of
      the DOCK180 family, as a molecule essential for ChC cartridge and bouton
      development. Furthermore, we present evidence that DOCK7 functions as a
      cytoplasmic activator of the schizophrenia-associated ErbB4 receptor tyrosine
      kinase and that DOCK7 modulates ErbB4 activity to control ChC cartridge and
      bouton development. Thus, our findings define DOCK7 and ErbB4 as key components
      of a pathway that controls the morphological differentiation of ChCs, with
      implications for the pathogenesis of schizophrenia.

PMID- 24440722
TI  - On the coherence between mathematical models of DSB repair and physiological
      reality.

PMID- 24440723
TI  - [Editor's Commentary. Pediatrics in Hungary].

PMID- 24440721
TI  - Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally
      to promote genome integrity.
AB  - Human RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because
      it is a fusion between a helicase and an essential replication factor. Budding
      yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like
      hRecQ4, is a robust 3'-5' helicase. Additionally, Hrq1 has the unusual property
      of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage
      phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere
      addition to DNA breaks. Both activities are rare; their coexistence in a single
      protein is unprecedented. Resistance to ICLs requires helicase activity, but
      suppression of telomere addition does not. Hrq1 also affects telomere length by a
      noncatalytic mechanism, as well as telomerase-independent telomere maintenance.
      Because Hrq1 binds telomeres in vivo, it probably affects them directly. Thus,
      the tumor-suppressing activity of RecQ4 could be due to a role in ICL repair
      and/or suppression of de novo telomere addition.

PMID- 24440720
TI  - ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma
      tumor-initiating cell state.
AB  - Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating
      cells (TICs) that are self-renewing and multipotent. To understand the regulation
      of the TIC state, we performed an image-based screen for genes regulating GBM TIC
      maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is
      required to maintain TIC-associated and normal human neural precursor cell
      phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its
      suppression increases glioma-free survival in intracranial xenografts. ZFHX4
      interacts with CHD4, a core member of the nucleosome remodeling and deacetylase
      (NuRD) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and
      control similar gene expression programs. Using expression data derived from GBM
      patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression
      perturbations, which defines ZFHX4 as a master regulator of CHD4. These
      observations define ZFHX4 as a regulatory factor that links the chromatin
      remodeling NuRD complex and the GBM TIC state. 

PMID- 24440724
TI  - [Pathogenesis of anorexia nervosa. Neurobiological risk factors and possible
      endophenotypes].
AB  - Anorexia nervosa is a serious, chronical state of illness which often starts in
      childhood or adolescence and has serious consequences on the quality of life.
      This review focuses on the heterogenity of the disease with emphasis on special
      diagnostic implications in case of childhood onset. Research findings of the last
      decade showed that genetic and neurobiological vulnerabilities are at least as
      potent risk factors as psychological, family constellations and sociocultural
      preferences. The heritability of eating disorders levels those of diseases
      predominantly influenced by biological factors. The authors give a summary of the
      most investigated neurobiologic and neurocognitive factors which could be the
      fundaments of a biological vulnerablilty. To date, no common risk factor could be
      identified, but some existing adversities can clearly be related to distinct
      subgroups with the disorder. The concept of endo- and subphenotypes leads to more
      specific and more efficient methods of therapy in other somatic and psychiatric
      diseases.

PMID- 24440725
TI  - [Ultrasound examination in childhood: new perspectives].
AB  - Everyday use of the modern imaging techniques such as CT, MRI, isotope, PET/CT
      decreased the reputation and importance of ultrasound. In some cases, ultrasound
      is only the first exploratory imaging method. Using the latest multi-slice CT,
      imaging can be performed in seconds, which led to a dramatic increase in the
      number of CT exams. However, this also means a significant radiation exposure to
      children, while US still harmless in this regard. In addition, significant
      progress has been made in ultrasound technology in recent years, which led an
      improvement in image quality. Children are ideal subjects for US examination as
      they usually have smaller weight with less body fat. Thus, ultrasound examination
      is easy to perform with a high frequency transducer resulting in much more
      detailed and higher resolution than in adults. With adequate equipment and
      experienced examiner in pediatric radiology, almost all parts of the body can be
      examined, making this technique as the first (sometimes together with X-ray) and,
      in most cases, the ultimate imaging exam for the diagnosis. This article will
      discuss the possibilities where ultrasound performed with a modern device is
      sufficient for an accurate diagnosis.

PMID- 24440726
TI  - [Importance of diabetic nephropathy in childhood. Clinical findings and basic
      research in recent decades].
AB  - Over the past decades diabetes mellitus is becoming a global pandemic affecting
      more than 371 million people worldwide. Parallel with the increasing prevalence
      of type 1 diabetes, there is a growing number of type 2 diabetes cases among
      children and adolescents that poses new challenges to pediatricians. Diabetic
      nephropathy is one of the major causes of end stage renal disease, developing in
      approximately 30% of diabetic patients. However, overt nephropathy is rare in
      childhood; screening and ongoing assessment for the earliest manifestation of
      renal injury is extremely important in this young population, as well. Although
      in the past decades intensive research activity focused on understanding of the
      pathomechanism of diabetic nephropathy and invention of new therapeutic
      approaches, prevention and definitive care are still urgently needed. The
      clinical section of the article summarizes the present state of epidemiology,
      diagnosis and current therapies of childhood diabetic nephropathy. Then, the
      authors discuss the state of basic research and show a few promising targets for
      drug development.

PMID- 24440727
TI  - [Ministers and ministries in charge of health care after World War II].

PMID- 24440728
TI  - [The Bible -- a medical approach. XII. Susannah and the old men peeping.
      Misbeliefs about twin pregnancies].

PMID- 24440730
TI  - [Lymphohistiocytic activation syndrome (LHAS)].
AB  - Lymphohistiocytic activation syndrome (LHAS) is related to inappropriate
      stimulation of macrophage cells in bone marrow and lymphoid system. LHAS combines
      the non-specific clinical signs (fever, poor general condition,
      hepatosplenomegaly, lymphadenopathy) and suggestive biological elements (bi-or
      pancytopenia, abnormal liver function, coagulopathy, increased LDH, ferritin and
      triglycerides). The diagnosis of SALH remains an emergency every clinician should
      discuss before any febrile cytopenia. The etiology of LHAS is still obscure, but
      recent advances in the genetic study of familial forms provide some essential
      elements in understanding. 

PMID- 24440731
TI  - [Prolonged phase II neuromuscular blockade following succinylcholine
      administration].
AB  - Patients who are given a single dose of succinylcholine normally undergo a short
      acting depolarizing phase I neuromuscular block but rarely a phase II block.
      Prolonged neuromuscular blockade occurs after a single dose of succinylcholine in
      case of genetically determined abnormal plasma butyrylcholinesterase activity. It
      is mandatory to use monitoring to detect this side effect. We report a case of a
      patient with abnormal plasma butyrylcholinesterase activity undergoing a six-hour
      prolonged neuromuscular phase II block, after a single dose of succinylcholine. 

PMID- 24440732
TI  - [Prehabilitation. Preparing patients for surgery to improve functional recovery
      and reduce postoperative morbidity].
AB  - OBJECTIVE: Prehabilitation consists in providing a repetitive physical exercise
      before surgery to improve the postoperative recovery course. This review aims to
      evaluate the feasibility and the expected benefits of prehabilitation on the
      postoperative recovery course and the reduction of the postoperative morbidity.
      DATA SOURCES: Data research has focused on English-language articles in the
      Medline database, published from 1989 to 2013. Keywords, used separately or in
      combination, were: prehabilitation, functional capacity, postoperative morbidity,
      physical activity. STUDY SELECTION: Selected articles were original articles,
      clinical cases, review articles and meta-analysis. DATA EXTRACTION: Articles were
      analyzed for feasibility, benefits and limitations of preoperative physical
      preparation techniques. DATA SYNTHESIS: Poor preoperative functional status is
      associated with increased postoperative morbidity. Elderly are more prone to
      postoperative complications. The improvement of preoperative physical status of
      these patients is possible and may reduce morbidity and allow faster recovery
      after major surgery. In order to improve efficiency, the training program must
      provide endurance and muscle reinforcement exercises, whose intensity must be
      adapted to the patient's baseline physical abilities. An average of three
      sessions per week over a period of six to eight weeks before surgery seemed a
      good compromise between feasibility and effectiveness. CONCLUSION: The
      effectiveness of prehabilitation has been demonstrated in cardiovascular surgery
      and probably in abdominal surgery. Prehabilitation must be integrated into the
      overall patient medical management, and must be associated with preoperative
      refeeding and postoperative rehabilitation protocols. By optimizing all stages of
      the surgical patient management, from diagnosis to recovery, prognosis of high
      risk surgical patients could be improved.

PMID- 24440733
TI  - [Moroccan survey about neuromuscular relaxant blocking drugs use and reversal
      management].
AB  - OBJECTIVE: To determine current clinical neuromuscular use in Morocco anesthetic
      practice. STUDY DESIGN: Clinical practice survey. METHODS: Anesthesiologists were
      invited to answer anonymously to question about neuromuscular blocking agents
      (NMBA): pharmacology, monitoring and antagonism drug use. Corrected yates test
      was used to compare qualitative parameters and variance analysis for quantitative
      parameters. P<0.05 was considered as significant. RESULTS: We had 171 answers,
      54% were paramedics (n=93) and 46% (n=78) were physicians (20% global effective
      in Morocco). Fifty-five percent were seniors. Vecuronium was the most NMBA used
      in Morocco for 51% of the anesthesiologists. Mean action time of NMBA was
      underestimate in more than 60% of the staff questioned specially for seniors
      (24.6%) than juniors (19.2%). Residual neuromuscular blockade was evaluated only
      by clinical and spirometric parameters in 72%. TOF monitor was used in 18% more
      in military hospitals (36%) and insurance clinics (40%) than private hospitals
      (12.5%). Administration of reversal drugs was systematic in 5.8% of
      anesthesiologists, frequent for 36.3% and rare for 55%. CONCLUSIONS: This study
      show an underestimation of residual neuromuscular blockade, poor neuromuscular
      monitor use and lack of knowledge of NMBA specially for senior anesthesiologists
      and in private hospitals. We should elaborate Moroccan guideline for NMBA use and
      provide formal training programs for our anesthetic staff.

PMID- 24440734
TI  - [Extracorporeal membrane oxygenation for refractory hypoxia secondary to a severe
      viral pneumonia due to influenza A (H1N1) in a pregnant woman: continuation or
      termination of pregnancy?].

PMID- 24440735
TI  - 35th Congress of the French association of neuro-anesthesiology and critical
      care.

PMID- 24440736
TI  - Recombinant adenovirus encoding FAT10 small interfering RNA inhibits HCC growth
      in vitro and in vivo.
AB  - Hepatocellular carcinoma is an aggressive and rapidly fatal malignancy
      representing the common cancer worldwide. The specific cellular gene involved in
      carcinogenesis has not been fully characterized. The ubiquitin-like modifier
      FAT10, recently reported to be overexpressed in 90% of hepatocellular carcinoma
      carcinomas, was attributed to transcriptional upregulation upon the loss of p53
      and induced chromosome instability in long-term in vitro culture. However, the
      exact function of FAT10 in hepatocellular carcinoma is not clear. In the present
      study, we utilized adenovirus-mediated RNA interference to knock down FAT10
      expression in hepatocellular carcinoma cells and observed its effects on
      hepatocellular carcinoma cell growth in vitro and in vivo. The results
      demonstrated that interference of FAT10 could inhibit cell proliferation by
      inhibiting the cell cycle S-phase entry and inducing cell apoptosis. In addition,
      in vivo experiments showed that adenovirus Ad-siRNA/FAT10 significantly
      suppressed tumor growth and prolonged the lifespan of tumor-bearing mice. These
      results suggest that knockdown of FAT10 by adenovirus-delivered siRNA may be a
      promising therapeutical strategy for treatment of hepatocellular carcinoma. 

PMID- 24440737
TI  - Healthy eating in summer day camps: the Healthy Lunchbox Challenge.
AB  - OBJECTIVE: To describe the development and evaluation of Healthy Lunchbox
      Challenge, a nutrition program targeting staff, parents, and children in summer
      day camps (SDCs). METHODS: A single-group, pre/post-assessment design was used
      during summer, 2011(baseline) and 2012 (intervention). Four community-based SDCs
      in South Carolina participated. Intervention components were applied over the 11
      week SDC program (2012) and consisted of (1) parent/staff education on Building a
      Better Lunchbox, and (2) a child/staff incentive program. Child and staff foods
      and beverages were assessed via direct observation (1,977 children and 241
      staff). Percentages of foods and beverages brought by children and staff during
      the intervention were compared with baseline measures using mixed-effects
      regression models. RESULTS: The percentage of children bringing fruits,
      vegetables, and water increased from 31% to 42% (P = .01), 5% to 16% (P = .01),
      and 47% to 60% (P = .01) from baseline to post-assessment. Staff fruits and
      vegetables increased from 30% to 47% (P = .03) and 9% to 22% (P = .03). A slight
      decrease was observed for staff water (64% to 58%); however, this was not
      statistically significant. Decreases in low-nutrient-dense foods and beverages
      were also observed. CONCLUSIONS AND IMPLICATIONS: The Healthy Lunchbox Challenge
      represents a low-cost, innovative way to influence the nutritional content of
      child and staff foods and beverages in SDCs.

PMID- 24440738
TI  - Safe laboratory handling of Neisseria meningitidis.
AB  - Transmission of Neisseria meningitidis mainly occurs by formation of aerosols
      generated in the nasopharynx. Working with meningococci in vitro and performing
      manipulations where aerosols may be generated may result in laboratory acquired
      infections if appropriate safety precautions are not taken. This review details
      the practical aspects and experience of safe working with N. meningitidis in the
      laboratory. The specific risk factor for laboratory-acquired infection is
      exposure to aerosols containing meningococci. Prevention should therefore focus
      on the use of microbiology safety cabinets during manipulation of meningococci
      and this should be reflected in local risk assessments, supported by safe
      practices of work appropriate facilities and equipment, training/competency and
      immunisation policies.

PMID- 24440739
TI  - Antimicrobial susceptibility data for Brucella melitensis isolates cultured from
      UK patients.

PMID- 24440740
TI  - TRPV4: new therapeutic target for inflammatory bowel diseases.
AB  - The transient receptor potential vanilloid-4 (TRPV4) belongs to a family of ion
      channels and can be activated by warm temperature, hypotonicity, cell swelling or
      lipid mediators of the arachidonic cascade. The metabolites or events responsible
      for TRPV4 activation are associated with inflammation, arguing in favor of a role
      for this receptor in inflammatory diseases. The first studies have focused their
      attention on the role of TRPV4 in neurons and endothelial cells but TRPV4
      cellular distribution is widespread, particularly in the gastrointestinal tract.
      Herein, we review a number of studies demonstrating the expression of TRPV4 in
      the gut, the regulation of its expression and functions by inflammatory mediators
      in that organ and the consequences of TRPV4 activation or inhibition in the
      intestine. We further discuss the relevance of considering this receptor as a
      potential target for therapeutic development in inflammatory bowel diseases. 

PMID- 24440741
TI  - Protein kinase C isoforms in atherosclerosis: pro- or anti-inflammatory?
AB  - Atherosclerosis is a pathologic condition caused by chronic inflammation in
      response to lipid deposition in the arterial wall. There are many known
      contributing factors such as long-term abnormal glucose levels, smoking,
      hypertension, and hyperlipidemia. Under the influence of such factors, immune and
      non-immune effectors cells are activated and participate during the progression
      of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the
      signal transduction pathways of cellular activation and have been associated with
      several aspects of the atherosclerotic vascular disease. This review article
      summarizes the current knowledge of PKC isoforms functions during atherogenesis,
      and addresses differential roles and disputable observations of PKC isoforms.
      Among PKC isoforms, both PKCbeta and PKCdelta are the most attractive and
      potential therapeutic targets. This commentary discusses in detail the outcomes
      and current status of clinical trials on PKCbeta and PKCdelta inhibitors in
      atherosclerosis-associated disorders like diabetes and myocardial infarction. The
      risk and benefit of these inhibitors for clinical purposes will be also
      discussed. This review summarizes what is already being done and what else needs
      to be done in further targeting PKC isoforms, especially PKCbeta and PKCdelta,
      for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in
      the future. 

PMID- 24440742
TI  - Notoginsenoside Ft1 activates both glucocorticoid and estrogen receptors to
      induce endothelium-dependent, nitric oxide-mediated relaxations in rat mesenteric
      arteries.
AB  - Panax notoginseng (Burk.) F.H. Chen has been used traditionally for the treatment
      of cardiovascular diseases. Notoginsenoside Ft1 (Ft1) is a bioactive saponin from
      the leaves of P. notoginseng. Experiments were designed to determine whether or
      not Ft1 is an endothelium-dependent vasodilator. Rat mesenteric arteries were
      suspended in organ chambers for the measurement of isometric tension during
      phenylephrine-induced contractions. The cyclic guanosine monophosphate (cGMP)
      level was assessed using enzyme immunoassay. The phosphorylation and protein
      expressions of endothelial nitric oxide synthase (eNOS), glucocorticoid receptors
      (GR), estrogen receptors beta (ERbeta), protein kinase B (Akt) and extracellular
      signal-regulated kinase 1/2 (ERK1/2) were determined by Western blotting. The
      localization of GR and ERbeta were determined by immunofluorescence staining. Ft1
      caused endothelium-dependent relaxations, which were abolished by l-NAME
      (inhibitor of nitric oxide synthases) and ODQ (inhibitor of soluble guanylyl
      cyclase). Ft1 increased the cGMP level in rat mesenteric arteries. GR and ERbeta
      were present in the endothelial layer and their antagonism by RU486 and PHTPP,
      respectively, inhibited Ft1-induced endothelium-dependent relaxations and
      phosphorylations of eNOS, Akt and ERK1/2. Inhibition of phosphoinositide-3-kinase
      (PI3K) by wortmannin and ERK1/2 by U0126 reduced Ft1-evoked relaxations and eNOS
      phosphorylation. Taken in conjunction, the present findings suggest that Ft1
      stimulates endothelial GRs and ERbetas with subsequent activation of the PI3K/Akt
      and ERK1/2 pathways in rat mesenteric arteries. This results in phosphorylation
      of eNOS and the release of NO, which activates soluble guanylyl cyclase in the
      vascular smooth muscle cells leading to relaxations. 

PMID- 24440743
TI  - Systematic misregistration and the statistical analysis of surface data.
AB  - Spatial normalisation is a key element of statistical parametric mapping and
      related techniques for analysing cohort statistics on voxel arrays and surfaces.
      The normalisation process involves aligning each individual specimen to a
      template using some sort of registration algorithm. Any misregistration will
      result in data being mapped onto the template at the wrong location. At best,
      this will introduce spatial imprecision into the subsequent statistical analysis.
      At worst, when the misregistration varies systematically with a covariate of
      interest, it may lead to false statistical inference. Since misregistration
      generally depends on the specimen's shape, we investigate here the effect of
      allowing for shape as a confound in the statistical analysis, with shape
      represented by the dominant modes of variation observed in the cohort. In a
      series of experiments on synthetic surface data, we demonstrate how allowing for
      shape can reveal true effects that were previously masked by systematic
      misregistration, and also guard against misinterpreting systematic
      misregistration as a true effect. We introduce some heuristics for disentangling
      misregistration effects from true effects, and demonstrate the approach's
      practical utility in a case study of the cortical bone distribution in 268 human
      femurs. 

PMID- 24440744
TI  - Dietary citrus pulp reduces lipid oxidation in lamb meat.
AB  - This study investigated the effect of replacing cereal concentrates with high
      levels of dried citrus pulp in the diet on lamb meat oxidative stability. Over 56
      days, lambs were fed a barley-based concentrate (Control) or concentrates in
      which 24% and 35% dried citrus pulp were included to partially replace barley
      (Citrus 24% and Citrus 35%, respectively). Meat was aged under vacuum for 4 days
      and subsequently stored aerobically at 4  degrees C. The Control diet increased
      the redness, yellowness and saturation of meat after blooming (P<0.01).
      Regardless of the level of supplementation, dietary dried citrus pulp strongly
      reduced meat lipid oxidation over 6 days of aerobic storage (P<0.001), while
      colour parameters did not change noticeably over storage and their variation rate
      was not affected by the diet. In conclusion, replacing cereals with dried citrus
      pulp in concentrate-based diets might represent a feasible strategy to naturally
      improve meat oxidative stability and to promote the exploitation of this by
      product.

PMID- 24440746
TI  - A practical approach for the detection of DNA nanostructures in single live human
      cells by fluorescence microscopy.
AB  - In the last decade, in vivo studies have revealed that even subtle differences in
      size, concentration of components, cell cycle stage, make the cells in a
      population respond differently to the same stimulus. In order to characterize
      such complexity of behavior and shed more light on the functioning and
      communication amongst cells, researchers are developing strategies to study
      single live cells in a population. In this paper, we describe the methods to
      design and prepare DNA-based fluorescent tetrahedral nanostructures, to deliver
      them to live cells and characterize such cells with epifluorescence microscopy.
      We report that HeLa cells internalize these nanostructures spontaneously with a
      higher efficiency with respect to single-stranded or double-stranded
      oligonucleotides. Our findings suggest that DNA tetrahedra could serve as a
      platform for the realization of a series of multifunctional intracellular
      biosensors for the analysis of single live cells. 

PMID- 24440747
TI  - Hic-5 influences genomic and non-genomic actions of the androgen receptor in
      prostate myofibroblasts.
AB  - There is extensive knowledge of androgen receptor (AR) signaling in cancer cells,
      but less regarding androgen action in stromal cells of the tumor
      microenvironment. We report here the genome-wide effects of a stromal cell
      specific molecular adapter and AR coregulator, hydrogen peroxide-inducible gene 5
      (Hic-5/TGFB1I1), on AR function in prostate myofibroblasts. Following androgen
      stimulation, Hic-5 rapidly translocates to the nucleus, coincident with increased
      phosphorylation of focal adhesion kinase. As a coregulator, Hic-5 acted to
      amplify or inhibit regulation of approximately 50% of AR target genes, affected
      androgen regulation of growth, cell adhesion, motility and invasion. These data
      suggest Hic-5 as a transferable adaptor between focal adhesions and the nucleus
      of prostate myofibroblasts, where it acts a key mediator of the specificity and
      sensitivity of AR signaling. We propose a model in which Hic-5 coordinates AR
      signaling with adhesion and extracellular matrix contacts to regulate cell
      behavior in the tumor microenvironment. 

PMID- 24440745
TI  - Methods for studying oogenesis.
AB  - Drosophila oogenesis is an excellent system for the study of developmental cell
      biology. Active areas of research include stem cell maintenance, gamete
      development, pattern formation, cytoskeletal regulation, intercellular
      communication, intercellular transport, cell polarity, cell migration, cell
      death, morphogenesis, cell cycle control, and many more. The large size and
      relatively simple organization of egg chambers make them ideally suited for
      microscopy of both living and fixed whole mount tissue. A wide range of tools is
      available for oogenesis research. Newly available shRNA transgenic lines provide
      an alternative to classic loss-of-function F2 screens and clonal screens. Gene
      expression can be specifically controlled in either germline or somatic cells
      using the Gal4/UAS system. Protein trap lines provide fluorescent tags of
      proteins expressed at endogenous levels for live imaging and screening
      backgrounds. This review provides information on many available reagents and key
      methods for research in oogenesis. 

PMID- 24440748
TI  - Regulatory feedback loop between T3 and microRNAs in renal cancer.
AB  - microRNAs, short non-coding RNAs, influence key physiological processes,
      including hormonal regulation, by affecting the expression of genes. In this
      study we hypothesised that the expression of microRNAs targeting thyroid hormone
      pathway genes may be in turn regulated by thyroid hormone signalling. It is known
      that the expression of DIO1, a gene contributing to triiodothyronine (T3)
      signalling, is regulated by miR-224. Thus, we analysed mutual regulation between
      triiodothyronine pathway and miR-224/miR-452/GABRE cluster. Firstly, we found
      that miR-452 directly regulates the expression of thyroid hormone receptor
      TRbeta1 in renal cancer cells. In turn, the expression of miR-224/452/GABRE
      cluster and other microRNAs targeting TRbeta1 was influenced by T3 treatment
      and/or TR silencing. miR-452 expression correlated with intracellular T3
      concentrations in renal tumours. In conclusion, we propose a new mechanism of
      feedback regulation, by which in renal cancer microRNAs regulate the expression
      of T3 pathway genes, while T3 in turn regulates expression of microRNAs. 

PMID- 24440749
TI  - Investigating a race model account of executive control in rats with the
      countermanding paradigm.
AB  - The countermanding paradigm investigates the ability to withhold a response when
      a stop signal is presented occasionally. The race model (Logan and Cowan, 1984)
      was developed to account for performance in humans and to estimate the stop
      signal response time (SSRT). This model has yet to be fully validated for
      countermanding performance in rats. Furthermore, response adjustments observed in
      human performance of the task have not been examined in rodents. Male Wistar rats
      were trained to respond to a visual stimulus (go signal) by pressing a lever
      below that stimulus, but to countermand the lever press (25% of trials)
      subsequent to an auditory tone (stop signal) presented after a variable delay. We
      found decreased inhibitory success as stop signal delay (SSD) increased and
      estimated a SSRT of 157ms. As expected by the race model, response time (RT) of
      movements that escaped inhibition: (1) were faster than responses made in the
      absence of a stop signal; (2) lengthened with increasing SSD; and (3) were
      predictable by the race model. In addition, responses were slower after stop
      trial errors, suggestive of error monitoring. Amphetamine (AMPH) (0.25, 0.5mg/kg)
      resulted in faster go trial RTs, baseline-dependent changes in SSRT and
      attenuated response adjustments. These findings demonstrate that the race model
      of countermanding performance, applied successfully in human and nonhuman primate
      models, can be employed in the countermanding performance of rodents. This is the
      first study to reveal response adjustments and AMPH-induced alterations of
      response adjustments in rodent countermanding. 

PMID- 24440750
TI  - Elevated BDNF mRNA expression in the medial prefrontal cortex after d-amphetamine
      reinstated conditioned place preference in rats.
AB  - Drug addiction behavior that is established and maintained by psychostimulants
      has been shown to be associated with the expression of brain-derived neurotrophic
      factor (BDNF) in the mesolimbic dopamine (DA) system. Cocaine has been used for
      most prior studies testing this effect of psychostimulants and therefore
      relatively little is known about its counterpart amphetamine (AMP). To fill this
      gap, the present study was designed to test whether BDNF mRNA expression levels
      in the DA terminal regions were changed specifically by d-AMP-induced conditioned
      place preference (CPP) followed by drug-primed reinstatement. The dose of d-AMP,
      1mg/kg, was confirmed to significantly induce CPP. Using this dose, a group of
      rats was initially subjected to d-AMP CPP, which was followed by entry into an
      extinction protocol with an additional 3-day withdrawal before a drug-primed
      reinstatement test was carried out. Following extinction of d-AMP CPP, a lower
      dose of d-AMP, namely 0.75mg/kg, was able to significantly reinstate CPP. The
      BDNF mRNA levels in the selected brain areas were determined by real-time
      polymerase chain reaction (PCR) after the CPP and reinstatement. The BDNF mRNA
      level in the medial prefrontal cortex (mPFC) was significantly increased after
      the reinstatement, but not the CPP test. And, none of the other four assessed
      brain areas showed any change in BDNF mRNA level after d-AMP CPP or
      reinstatement. These findings support the notion that BDNF is involved in drug
      seeking behavior and indicate that d-AMP reinstatement after extinction may be
      linked to an increase in BDNF mRNA expression in the mPFC. 

PMID- 24440751
TI  - Placebo treatment can alter primary visual cortex activity and connectivity.
AB  - Placebo treatment can alter brain activation in regions implicated in affective
      processing and cognitive control of emotions. This functional magnetic resonance
      imaging (fMRI) study investigated whether a placebo can additionally modulate
      visual cortex activity and connectivity during affective picture perception. The
      participants underwent a retest design where they were presented with disgusting,
      fear-eliciting and neutral pictures both with, and without a placebo (inert pill
      presented with the suggestion that it can reduce disgust symptoms). The placebo
      provoked a strong decrease in experienced disgust. This was accompanied by a
      reduced activation of the primary visual cortex, which showed reduced interaction
      with the amygdala and the insula. Accordingly, placebos are able to affect basic
      perceptive processes. 

PMID- 24440752
TI  - Emergence of a 600-Hz buzz UP state Purkinje cell firing in alert mice.
AB  - Purkinje cell (PC) firing represents the sole output from the cerebellar cortex
      onto the deep cerebellar and vestibular nuclei. Here, we explored the different
      modes of PC firing in alert mice by extracellular recording. We confirm the
      existence of a tonic and/or bursting and quiescent modes corresponding to UP and
      DOWN state, respectively. We demonstrate the existence of a novel 600-Hz buzz UP
      state of firing characterized by simple spikes (SS) of very small amplitude.
      Climbing fiber (CF) input is able to switch the 600-Hz buzz to the DOWN state, as
      for the classical UP-to-DOWN state transition. Conversely, the CF input can
      initiate a typical SS pattern terminating into 600-Hz buzz. The 600-Hz buzz was
      transiently suppressed by whisker pad stimulation demonstrating that it remained
      responsive to peripheral input. It must not be mistaken for a DOWN state or the
      sign of PC inhibition. Complex spike (CS) frequency was increased during the 600
      Hz buzz, indicating that this PC output actively contributes to the cerebello
      olivary loop by triggering a disinhibition of the inferior olive. During the 600
      Hz buzz, the first depolarizing component of the CS was reduced and the second
      depolarizing component was suppressed. Consistent with our experimental
      observations, using a 559-compartment single-PC model - in which PC UP state (of
      about -43mV) was obtained by the combined action of large tonic AMPA conductances
      and counterbalancing GABAergic inhibition - removal of this inhibition produced
      the 600-Hz buzz; the simulated buzz frequency decreased following an artificial
      CS. 

PMID- 24440753
TI  - Modulating autophagy affects neuroamyloidogenesis in an in vitro ischemic stroke
      model.
AB  - AIMS: To explore the effects of modulating autophagy on neuroamyloidogenesis in
      an ischemic stroke model of cultured neuroblastoma 2a (N2a)/Amyloid precursor
      protein (APP)695 cells. METHODS: The ischemic stroke model of N2a/APP695 cells
      was made by 6h oxygen-glucose deprivation/12h reperfusion (OGDR). Drug
      administration of 3-methyladenine (3-MA), rapamycin or dl-3-n-butylphthalide
      (NBP) was started at the beginning of the OGDR and lasted until the end of
      reperfusion, in order to explore their effects on N2a/APP695 cells under OGDR
      conditions. Then the cells were incubated in the drug-free and full culture
      medium under normoxic conditions for 12h. Cell viability and injury were
      investigated. The key proteins of nuclear factor kappa B (NF-kappaB) pathway and
      a key component of autophagy Beclin 1 were detected by Western blotting;
      immunofluorescence double-staining of amyloid-beta (Abeta)1-42 with Beclin 1 was
      performed to investigate their cellular co-localization relationship; beta
      secretase and gamma-secretase activity assay and Abeta1-42 enzyme-linked
      immunosorbent assay were performed to investigate the amyloidogenesis. RESULTS:
      The results showed that, OGDR enhanced cell injury, autophagy activity,
      neuroinflammation and Abeta generation in N2a/APP695 cells; down-regulating
      autophagy by 3-MA and NBP increased cell viability, decreased lactate
      dehydrogenase (LDH) production, inhibited the activation of NF-kappaB pathway,
      suppressed beta- and gamma-secretase activities and Abeta generation; while up
      regulating autophagy by rapamycin got the opposite results; immunofluorescence
      double-staining results showed elevated Abeta1-42(+) signal was co-localized with
      Beclin 1(+) signal. CONCLUSION: Our data suggested that down-regulating autophagy
      may inhibit ischemia-induced neuroamyloidogenesis via suppressing the activation
      of NF-kappaB pathway. This study might help us to find a new therapeutic strategy
      to prevent brain ischemic damage and depress the risk of post-stroke dementia.

PMID- 24440754
TI  - Haloperidol-induced Nur77 expression in striatopallidal neurons is under the
      control of protein phosphatase 1 regulation by DARPP-32.
AB  - Impaired dopaminergic signaling in the striatum is involved in diseases as
      diverse as Parkinson's disease, addiction, and schizophrenia. An important
      pathophysiological aspect is the loss of balance between striatopallidal and
      striatonigral pathways. Nur77 is an orphan nuclear receptor and dopamine
      regulated immediate-early gene. Classical antipsychotic drugs widely used in the
      treatment of schizophrenia, such as haloperidol, increase Nur77 mRNA expression
      in the striatum. However, little is known about the intracellular signaling
      pathways involved in Nur77 induction. Here, using pharmacological approaches and
      transgenic mutant mice, we investigated the mechanisms underlying the up
      regulation of Nur77 protein expression in the dorsal striatum after haloperidol
      injection. In drd1a::EGFP transgenic mice that express GFP in D1 neurons, Nur77
      up-regulation induced by haloperidol occurred predominantly in GFP-negative
      neurons. In Galphaolf heterozygous mutant mice, in which cAMP production in
      response to A2A stimulation is impaired in the striatum, haloperidol effect was
      not altered. In contrast, in DARPP-32 knock-in mutant mice bearing a T34A point
      mutation of the site responsible for cAMP-dependent phosphatase 1 inhibition,
      Nur77 up-regulation by haloperidol was prevented. Haloperidol also induced Nur77
      protein in D2 neurons of the nucleus accumbens core of wild type but not T34A
      knock-in mice. Thus, our results show that expression of Nur77 is induced by
      haloperidol in D2 receptors-expressing medium-sized spiny neurons, through cAMP
      dependent regulation of protein phosphatase 1, which is likely to modulate the
      effects of other protein kinases. Our results clarify the mechanisms of Nur77
      induction by antipsychotic and its possible contribution to extrapyramidal
      effects. 

PMID- 24440756
TI  - Role of ERK/NFkappaB in vanadium (IV) oxide mediated osteoblast differentiation
      in C3H10t1/2 cells.
AB  - Vanadium (V) compounds are reported to have insulin mimicking action, which
      render them to show excellent osteogenic activity. In the current study we
      investigated the effect of various vanadium compounds on osteoblast
      differentiation of mouse mesenchymal stem cells, C3H10t1/2 cells, and analyzed
      the underlying mechanism of vanadium for this action. Our data showed that
      treatment of C3H10t1/2 cells with V (IV) oxide complex (at 7-25 MUM
      concentrations) induced osteoblast differentiation maximally as compared to V2O5.
      On the other hand, ammonium vanadate was found to dampen the osteoblast
      differentiation process. Based on this data, V (IV) oxide was investigated
      further to analyze its probable mode of action as an osteoblastic agent. The key
      factors implicated in osteoblast differentiation i.e., NFkappaB, ERK 1/2, AP1 and
      CRE were examined in response to V (IV) oxide exposure. Exposure to V (IV) oxide
      caused 2- and 5-folds induction of luciferase activities in cells transfected
      with SRE-luc and NFkappaB-luc reporter vectors respectively (p < 0.05). Further,
      exposure to V (IV) oxide enhanced the phosphorylation of ERK 1/2, IkappaB and
      NFkappaBp65 proteins. In addition, RT-PCR analysis, alizarin red staining and
      immunoblot analysis showed that inhibition of osteoblast differentiation in
      presence of PD98059 and parthenolide (inhibitors of ERK and NFkappaB pathways
      respectively) was rescued in presence of V (IV) oxide. These results suggest that
      V (IV) oxide up regulates osteoblast differentiation through ERK and NFkappaB
      pathways and hence could be utilized as an agent for bone formation after further
      analysis and validation.

PMID- 24440755
TI  - Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's
      action in vivo.
AB  - Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in
      about 80% of cocaine seized in the United States and linked to debilitating, and
      sometimes fatal, immunologic effects in cocaine abusers. One explanation for the
      addition of levamisole to cocaine is that it increases the amount of product and
      enhances profits. An alternative possibility, and one investigated here, is that
      levamisole alters cocaine's action in vivo. We specifically investigated effects
      of levamisole on cocaine's stereotypical and place-conditioning effects in an
      established invertebrate (planarian) assay. Acute exposure to levamisole or
      cocaine produced concentration-dependent increases in stereotyped movements. For
      combined administration of the two agents, isobolographic analysis revealed that
      the observed stereotypical response was enhanced relative to the predicted
      effect, indicating synergism for the interaction. In conditioned place preference
      (CPP) experiments, cocaine produced a significant preference shift; in contrast,
      levamisole was ineffective at all concentrations tested. For combination
      experiments, a submaximal concentration of cocaine produced CPP that was enhanced
      by inactive concentrations of levamisole, indicating synergism. The present
      results provide the first experimental evidence that levamisole enhances
      cocaine's action in vivo. Most important is the identification of synergism for
      the levamisole/cocaine interaction, which now requires further study in mammals. 

PMID- 24440757
TI  - All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC
      expression and granzyme B activity leading to impaired NK cell cytotoxicity.
AB  - NK cell is an innate immune system lymphocyte lineage with natural cytotoxicity.
      Its optimal use in the clinic requires in vitro expansion and activation.
      Cytokines and encounter with target cells activate NK cells and induce
      proliferation, and this could depend on the presence of other immune cells. Here
      we activated PBMCs during 5 days with IL-2, with IL-2 plus the tumor cell line
      K562 and with the lymphoblastoid cell line R69 and perform integrated analyses of
      microRNA and mRNA expression profiles of purified NK cells. The samples cluster
      depending on the stimuli and not on the donor, indicating that the pattern of NK
      cell stimulation is acutely well conserved between individuals. Regulation of
      mRNA expression is tighter than that of miRNA expression. All stimuli induce a
      common preserved genetic remodeling. In addition, encounter with target cells
      mainly activates pathways related to metabolism. Different target cells induce
      different NK cell remodeling which affects cytokine response and cytotoxicity,
      supporting the notion that encounter with different target cells significantly
      changing the activation pattern. We validate our analysis by showing that
      activation down regulates miR-23a, which is a negative regulator of cathepsin C
      (CTSC) mRNA, a gene up regulated by all stimuli. The peptidase CTSC activates the
      granzymes, the main effector proteases involved in NK cell cytotoxicity. All
      trans retinoic acid (ATRA), which induces miR-23a expression, decreases CTSC
      expression and granzyme B activity leading to impaired NK cell cytotoxicity in an
      in vivo mouse model. 

PMID- 24440758
TI  - Met endosomal signalling: in the right place, at the right time.
AB  - Deregulated signalling of the Receptor Tyrosine Kinase (RTK), Met, and/or its
      ligand HGF have been associated with cancer formation and progression to
      metastasis, with Met/HGF often overexpressed or mutated. Thus, Met has become a
      major target for cancer therapy and its inhibition is currently being tested in
      the clinic. It has recently become evident that, instead of signalling at the
      plasma membrane only, Met signals post-internalisation from endosomal
      compartments. Thus, Met endocytic trafficking is required for the full activation
      of signals such as Gab1, ERK 1/2, STAT3 and Rac1, all implicated in cell
      survival, invasion and metastasis. Modifications in the balance between
      degradation and recycling of Met may also impinge on Met signalling. Moreover,
      oncogenic Met mutations in the kinase domain trigger constitutive Met
      internalisation/recycling, leading to "endosomal signalling" and consequent cell
      transformation. Using Met as an example, this review outlines the evidence that
      the molecular mechanisms regulating trafficking and endosomal signalling may be
      exploited to design future cancer therapies. 

PMID- 24440759
TI  - The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer
      (START) domain proteins: new players in cholesterol metabolism.
AB  - Cholesterol levels in the body are maintained through the coordinated regulation
      of its uptake, synthesis, distribution, storage and efflux. However, the way
      cholesterol is sorted within cells remains poorly defined. The discovery of the
      newly described StarD4 subfamily, part of the steroidogenic acute regulatory
      lipid transfer (START) domain family of proteins, affords an opportunity for the
      study of intracellular cholesterol movement, metabolism and its disorders. The
      three members of this intracellular subfamily of proteins (StarD4, StarD5 and
      StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in
      particular), but differing regulation and localization. The ability to bind and
      transport cholesterol through a non-vesicular mean suggests that they play a
      previously unappreciated role in cholesterol homeostasis. 

PMID- 24440760
TI  - Effects of activated carbon on reductive dechlorination of PCBs by organohalide
      respiring bacteria indigenous to sediments.
AB  - Polychlorinated biphenyls (PCBs) have accumulated in aquatic sediments due to
      their inherent chemical stability and their presence poses a risk due to their
      potential toxicity in humans and animals. Granular activated carbon (GAC) has
      been applied to PCB contaminated sediment sites to reduce the aqueous
      concentration by sequestration thus reducing the PCB exposure and toxicity to
      both benthic and aquatic organisms. However, it is not known how the reduction of
      PCB bioavailability by adsorption to GAC affects bacterial transformation of PCBs
      by indigenous organohalide respiring bacteria. In this study, the impact of GAC
      on anaerobic dechlorination by putative organohalide respiring bacteria
      indigenous to sediment from Baltimore Harbor was examined. It was shown that the
      average Cl/biphenyl after dehalogenation of Aroclor 1260 was similar between
      treatments with and without GAC amendment. However, GAC caused a substantial
      shift in the congener distribution whereby a smaller fraction of highly
      chlorinated congeners was more extensively dechlorinated to mono- through tri
      chlorinated congeners compared to the formation of tri- through penta-chlorinated
      congeners in unamended sediment. The results combined with comparative sequence
      analysis of 16S rRNA gene sequences suggest that GAC caused a community shift to
      putative organohalide respiring phylotypes that coincided with more extensive
      dechlorination of ortho and unflanked chlorines. This shift in activity by GAC
      shown here for the first time has the potential to promote greater degradation in
      situ by promoting accumulation of less chlorinated congeners that are generally
      more susceptible to complete mineralization by aerobic PCB degrading bacteria. 

PMID- 24440761
TI  - Occurrence, behavior and removal of typical substituted and parent polycyclic
      aromatic hydrocarbons in a biological wastewater treatment plant.
AB  - Wastewater treatment plant (WWTP) effluent is the major source for substituted
      polycyclic aromatic hydrocarbons (SPAHs) to the receiving rivers, as well as the
      parent PAHs. Some of the SPAHs showed higher toxicities and levels than their
      parent PAHs. The occurrence and behavior of typical SPAHs were investigated in a
      representative biological WWTP in Beijing, China. Methyl PAHs (MPAHs) (149-221
      ng/L in the influent; 29.6-56.3 ng/L in the effluent; 202-375 ng/g in the
      activated sludge), oxygenated PAHs (OPAHs) (139-155 ng/L; 69.9-109 ng/L; 695-1533
      ng/g) and PAHs (372-749 ng/L; 182-241 ng/L; 2402-3321 ng/g) existed, but nitrated
      PAHs (NPAHs) were not detected. 2-Methylnaphthalene, anthraquinone, 9-fluorenone
      and 2-methylanthraquinone were the predominant SPAHs. OPAHs were deduced to be
      formed from PAHs especially during summer, based on the ratios variation and
      removal efficiencies of the two seasons, and the surplus mass in the outflows.
      Low molecular weight compounds (2-3 rings) might be mainly removed by
      mineralization/transformation and adsorption in the anaerobic unit, and by
      volatilization in the aerobic unit. High molecular weight compounds (4-6 rings)
      might be mainly removed by adsorption in the anaerobic unit. The total outflows
      of SPAHs and PAHs were 66 g/d in summer and 148 g/d in winter from the WWTP to
      the receiving river. The percentage of OPAHs was higher in summer than in winter.

PMID- 24440762
TI  - Kenyan purple tea anthocyanins and coenzyme-Q10 ameliorate post treatment
      reactive encephalopathy associated with cerebral human African trypanosomiasis in
      murine model.
AB  - Human African trypanosomiasis (HAT) is a tropical disease caused by two
      subspecies of Trypanosoma brucei, the East African variant T. b. rhodesiense and
      the West African variant T. b. gambiense. Melarsoprol, an organic arsenical, is
      the only drug used to treat late stage T. b. rhodesiense infection.
      Unfortunately, this drug induces an extremely severe post treatment reactive
      encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from
      this complication. A highly reproducible mouse model was adapted to assess the
      use of Kenyan purple tea anthocyanins and/or coenzyme-Q10 in blocking the
      occurrence of PTRE. Female Swiss white mice were inoculated intraperitoneally
      with approximately 10(4) trypanosome isolate T. b. rhodesiense KETRI 2537 and
      treated sub-curatively 21days post infection with 5mg/kg diminazene aceturate
      (DA) daily for 3days to induce severe late CNS infection that closely mirrors
      PTRE in human subjects. Thereafter mice were monitored for relapse of parasitemia
      after which they were treated with melarsoprol at a dosage of 3.6mg/kg body
      weight for 4days and sacrificed 24h post the last dosage to obtain brain samples.
      Brain sections from mice with PTRE that did not receive any antioxidant treatment
      showed a more marked presence of inflammatory cells, microglial activation and
      disruption of the brain parenchyma when compared to PTRE mice supplemented with
      either coenzyme-Q10, purple tea anthocyanins or a combination of the two. The
      mice group that was treated with coenzyme-Q10 or purple tea anthocyanins had
      higher levels of GSH and aconitase-1 in the brain compared to untreated groups,
      implying a boost in brain antioxidant capacity. Overall, coenzyme-Q10 treatment
      produced more beneficial effects compared to anthocyanin treatment. These
      findings demonstrate that therapeutic intervention with coenzyme-Q10 and/or
      purple tea anthocyanins can be used in an experimental mouse model to ameliorate
      PTRE associated with cerebral HAT. 

PMID- 24440763
TI  - [Dysimmun benign disease?].

PMID- 24440764
TI  - [Gastric signet ring cell adenocarcinoma: A distinct entity].
AB  - Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence
      is increasing. The pathologist plays a central role in the identification of this
      entity. Diagnosis is based on an adenocarcinoma containing a majority of signet
      ring cells (above 50 %). The prognosis of GSRC is the same as gastric
      adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a
      low sensitivity to chemotherapy. This review aimed to discuss the histological,
      the prognostic and the therapeutic aspect of this entity. 

PMID- 24440765
TI  - [Becoming doctor: Highlight the hidden curriculum. Medical error as an example].
AB  - Medical culture is both individual and collective. It is also implicit, hidden
      (hidden curriculum) and binding.It spreads and builds from the beginning of the
      training.It strongly impacts the personalities and professional care practices.
      Awareness of its existence and identification of its main lines are the first
      steps for fruitful research.

PMID- 24440766
TI  - [Bullous pemphigoid: Particular clinical and immuno-histological profil in a
      young woman].

PMID- 24440767
TI  - [A blocked preexcitation].

PMID- 24440768
TI  - [Influenza, influenza-like illness: from theory to practice].
AB  - In France, there are large discrepancies regarding flu between the severe disease
      described by Health Authorities and the disease that people face, considered as
      usual and benign. Flu prevention is useful, mainly through vaccination. For a
      well-established influenza-like illness, both individual measures dedicated to
      the limitation of the disease propagation and symptomatic treatment are to be
      initiated. Few clinical data are available regarding the most often used
      treatments for influenza-like illness (paracetamol, homeopathic and symptomatic
      treatments). The analysis did not show any decrease in the chances of success for
      patients with more often used drugs, either being under medical prescription,
      pharmacist advice or self-medication. In front of an influenza-like illness, the
      recommendations for daily practice can be based on 2 well-defined clinical
      situations: a specific management for patients at risk, and the influenza-like
      illness symptoms relief for the others, using a treatment specific for each
      patient. 

PMID- 24440769
TI  - [Localized tamponade: a rare cause of cardiac arrest of sudden onset].

PMID- 24440770
TI  - Importance of Internet surveillance in public health emergency control and
      prevention: evidence from a digital epidemiologic study during avian influenza A
      H7N9 outbreaks.
AB  - BACKGROUND: Outbreaks of human infection with a new avian influenza A H7N9 virus
      occurred in China in the spring of 2013. Control and prevention of a new human
      infectious disease outbreak can be strongly affected by public reaction and
      social impact through the Internet and social media. OBJECTIVE: This study aimed
      to investigate the potential roles of Internet surveillance in control and
      prevention of the human H7N9 outbreaks. METHODS: Official data for the human H7N9
      outbreaks were collected via the China National Health and Family Planning
      Committee website from March 31 to April 24, 2013. We obtained daily posted and
      forwarded number of blogs for the keyword "H7N9" from Sina microblog website and
      a daily Baidu Attention Index (BAI) from Baidu website, which reflected public
      attention to the outbreak. Rumors identified and confirmed by the authorities
      were collected from Baidu search engine. RESULTS: Both daily posted and forwarded
      number and BAI for keyword H7N9 increased quickly during the first 3 days of the
      outbreaks and remained at a high level for 5 days. The total daily posted and
      forwarded number for H7N9 on Sina microblog peaked at 850,000 on April 3, from
      zero blogs before March 31, increasing to 97,726 on April 1 and to 370,607 on
      April 2, and remaining above 500,000 from April 5-8 before declining to 208,524
      on April 12. The total daily BAI showed a similar pattern of change to the total
      daily posted and forwarded number over time from March 31 to April 12. When the
      outbreak locations spread, especially into other areas of the same province/city
      and the capital, Beijing, daily posted and forwarded number and BAI increased
      again to a peak at 368,500 and 116,911, respectively. The median daily BAI during
      the studied 25 days was significantly higher among the 7 provinces/cities with
      reported human H7N9 cases than the 2 provinces without any cases (P<.001). So
      were the median daily posted and forwarded number and daily BAI in each
      province/city except Anhui province. We retrieved a total of 32 confirmed rumors
      spread across 19 provinces/cities in China. In all, 84% (27/32) of rumors were
      disseminated and transmitted by social media. CONCLUSIONS: The first 3 days of an
      epidemic is a critical period for the authorities to take appropriate action
      through Internet surveillance to prevent and control the epidemic, including
      preparation of personnel, technology, and other resources; information release;
      collection of public opinion and reaction; and clarification, prevention, and
      control of rumors. Internet surveillance can be used as an efficient and
      economical tool to prevent and control public health emergencies, such as H7N9
      outbreaks.

PMID- 24440771
TI  - Src mediates ERK reactivation in gefitinib resistance in non-small cell lung
      cancer.
AB  - To study epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)
      resistance mechanisms, we established a novel gefitinib-resistant lung cancer
      cell line derived from an EGFR-mutant non-small cell lung cancer cell line (PC-9)
      pretreated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (designated PC9
      GR). We found that gefitinib substantially suppressed the EGFR signaling pathway,
      whereas ERK was reactivated after several hours in PC9-GR but not in PC-9. The
      combination of gefitinib with ERK inhibition (by U0126) restored gefitinib
      susceptibility in PC9-GR, but PI3K-Akt inhibition with LY294002 did not. Although
      the levels of phosphorylated Src were up-regulated simultaneously with ERK
      reactivation, neither ERK suppression using U0126 nor an ERK-specific siRNA
      induced Src phosphorylation. Furthermore, dual inhibition of EGFR and Src
      restored gefitinib sensitivity in PC9-GR in vitro and in vivo. In conclusion, our
      results indicate that Src-mediated ERK reactivation may play a role in a novel
      gefitinib resistance mechanism, and that the combined use of gefitinib with a Src
      inhibitor may be a potent strategy to overcome this resistance. 

PMID- 24440772
TI  - Design and construction of a modular low-cost epifluorescence upright microscope
      for neuron visualized recording and fluorescence detection.
AB  - BACKGROUND: One of the limitations when establishing an electrophysiology setup,
      particularly in low resource settings, is the high cost of microscopes. The
      average cost for a microscope equipped with the optics for infrared (IR) contrast
      or microfluorometry is $40,000. We hypothesized that optical elements and
      features included in commercial microscopes are not necessary to IR video
      visualize neurons or for microfluorometry. NEW METHOD: We present instructions
      for building a low-cost epifluorescence upright microscope suitable for
      visualized patch-clamp recording and fluorescence detection using mostly catalog
      available parts. RESULTS: This microscope supports applications such as
      visualized whole-cell recording using IR oblique illumination (IR-OI), or more
      complex applications such as microfluorometry using a photodiode. In both IR-OI
      and fluorescence, actual resolution measured with 2-MUm latex beads is close to
      theoretical resolution. The lack of movable parts to switch configurations
      ensures stability when doing intracellular recording. COMPARISON WITH EXISTING
      METHODS: The low cost is a significant advantage of this microscope compared to
      existent custom-built microscopes. The cost of the simplest configuration with IR
      OI is ~$2000, whereas the cost of the configuration with epifluorescence is
      ~$5000. Since this design does not use pieces discarded from commercial
      microscopes, it is completely reproducible. CONCLUSIONS: We suggest that this
      microscope is a viable alternative for doing in vitro electrophysiology and
      microfluorometry in low-resource settings. Characteristics such as an open box
      design, easy assembly, and low-cost make this microscope a useful instrument for
      science education and teaching for topics such as optics, biology, neuroscience,
      and for scientific "hands-on" workshops.

PMID- 24440773
TI  - Using Tweedie distributions for fitting spike count data.
AB  - BACKGROUND: The nature of spike count distributions is of great practical concern
      for the analysis of neural data. These distributions often have a tendency for
      'failures' and a long tail of large counts, and may show a strong dependence of
      variance on the mean. Furthermore, spike count distributions often show
      multiplicative rather than additive effects of covariates. We analyzed the
      responses of neurons in primary auditory cortex to transposed stimuli as a
      function of interaural time differences (ITD). In more than half of the cases,
      the variance of neuronal responses showed a supralinear dependence on the mean
      spike count. NEW METHOD: We explored the use of the Tweedie family of
      distributions, which has a supralinear dependence of means on variances. To
      quantify the effects of ITD on neuronal responses, we used generalized linear
      models (GLMs), and developed methods for significance testing under the Tweedie
      assumption. RESULTS: We found the Tweedie distribution to be generally a better
      fit to the data than the Poisson distribution for over-dispersed responses.
      COMPARISON WITH EXISTING METHODS: Standard analysis of variance wrongly assumes
      Gaussian distributions with fixed variance and additive effects, but even
      generalized models under Poisson assumptions may be hampered by the over
      dispersion of spike counts. The use of GLMs assuming Tweedie distributions
      increased the reliability of tests of sensitivity to ITD in our data.
      CONCLUSIONS: When spike count variance depends strongly on the mean, the use of
      Tweedie distributions for analyzing the data is advised.

PMID- 24440774
TI  - Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.
AB  - Reactive astrogliosis is an essential feature of astrocytic response to all forms
      of central nervous system (CNS) injury and disease, which may benefit or harm
      surrounding neural and non-neural cells. Despite extensive study, its molecular
      triggers remain largely unknown in term of ischemic stroke. In the current study
      we investigated the role p38 mitogen-activated protein kinase (MAPK) in
      astrogliosis both in vitro and in vivo. In a mouse model of middle cerebral
      artery occlusion (MCAO), p38 MAPK activation was observed in the glia scar area,
      along with increased glial fibrillary acidic protein (GFAP) expression. In
      primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was
      attenuated by both p38 inhibition and knockout of p38 MAPK. In addition, both
      knockout and inhibition of p38 MAPK also reduced astrocyte migration, but did not
      affect astrocyte proliferation. In a mouse model of permanent MCAO, no
      significant difference in motor function recovery and lesion volume was observed
      between conditional GFAP/p38 MAPK knockout mice and littermates. While a
      significant reduction of astrogliosis was observed in the GFAP/p38 knockout mice
      compared with the littermates. Our findings suggest that p38 MAPK signaling
      pathway plays an important role in the ischemic stroke-induced astrogliosis and
      thus may serve as a novel target to control glial scar formation. 

PMID- 24440775
TI  - Neuroprotective effects of amlodipine besylate and benidipine hydrochloride on
      oxidative stress-injured neural stem cells.
AB  - Hypertension is associated with oxidative stress. Amlodipine besylate (AB) and
      benidipine hydrochloride (BH), which are Ca(2+) antagonists, have been reported
      to reduce oxidative stress. In this study, we examined the neuroprotective
      effects of AB and BH on oxidative stress-injured neural stem cells (NSCs), with a
      focus on the phosphatidylinositol 3-kinase (PI3K) pathway and the extracellular
      signal-regulated kinase (ERK) pathway. After treatment with H2O2, the viability
      of NSCs decreased in a concentration-dependent manner; however, co-treatment with
      AB or BH restored the viability of H2O2-injured NSCs. H2O2 increased free radical
      production and apoptosis in NSCs, whereas co-treatment with AB or BH attenuated
      these effects. To evaluate the effects of AB or BH on the H2O2-inhibited
      proliferation of NSCs, we performed BrdU labeling and colony formation assays and
      found that NSC proliferation decreased upon H2O2 treatment but that combined
      treatment with AB or BH restored this proliferation. Western blot analysis showed
      that AB and BH increased the expression of cell survival-related proteins that
      were linked with the PI3K and ERK pathways but decreased the expression of cell
      death-related proteins. To investigate whether the PI3K and ERK pathways were
      directly involved in the neuroprotective effects of AB and BH on H2O2-treated
      NSCs, NSCs were pretreated with the PI3K inhibitor, LY294002, or the ERK
      inhibitor, FR180204, which significantly blocked the effects of AB and BH.
      Together, our results suggest that AB and BH restore the H2O2-inhibited viability
      and proliferation of NSCs by inhibiting oxidative stress and by activating the
      PI3K and ERK pathways. 

PMID- 24440776
TI  - Temporal profile of the vascular anatomy evaluated by 9.4-T magnetic resonance
      angiography and histopathological analysis in mice lacking RNF213: a
      susceptibility gene for moyamoya disease.
AB  - Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with
      unknown etiology. Recent genome-wide and locus-specific association studies
      identified RNF213 as an important MMD susceptibility gene. However, the exact
      mechanism by which an abnormality in RNF213 leads to MMD is unknown. To evaluate
      the role of RNF213 in the etiology of MMD, we generated RNF213-deficient mice
      (RNF213-/-) by deleting exon 32 of RNF213 by the Cre-lox system, and investigated
      whether they developed MMD. The temporal profile of cervical/intracranial
      arteries was evaluated by 9.4-T magnetic resonance angiography (MRA). The anatomy
      of the circle of Willis was analyzed by a trans-cardiac injection of carbon black
      dye. The common carotid arteries (CCA) were sectioned and the arterial wall
      thickness/thinness was evaluated by Elastica-Masson staining before and after CCA
      ligation, which selectively induced vascular hyperplasia. As a result, RNF213-/-
      grew normally, and no significant difference was observed in MRA findings, the
      anatomy of the circle of Willis, or vascular wall thickness/thinness between RNF
      /- and wild-type littermates (Wt.) under normal conditions until 64 weeks of age.
      However, Elastica-Masson staining demonstrated that both the intima and medial
      layer were significantly thinner after CCA ligation in RNF213-/- than in Wt.
      after 14 days (P<0.01). In conclusion, mice lacking the RNF213 gene did not
      spontaneously develop MMD, indicating that a functional loss of RNF213 did not
      sufficiently induce MMD. Suppression of vascular remodeling in RNF213-/- requires
      further examination to clarify the role of RNF213. 

PMID- 24440777
TI  - Involvement of the blood-brain barrier opening in cognitive decline in aged rats
      following orthopedic surgery and high concentration of sevoflurane inhalation.
AB  - The underlying causes of postoperative cognitive decline (POCD) in old patients
      remained unelucidated, and there are little descriptions on mechanisms associated
      with the blood-brain barrier (BBB) disruption during POCD. We therefore tested
      the effects of orthopedic surgery with different concentrations of sevoflurane
      for 2 h on the behavior test and the BBB permeability in aged rats. 18-month rats
      were divided into control group and surgical group with propofol anesthesia (0.7
      mgkg(-1) min(-1)) and 1.0 MAC, 1.3 MAC, and 1.5 MAC sevoflurane inhalation for 2
      h. We assessed their cognitive function via Y-maze and fear conditioning test on
      day 1, 3, and 7 after experiments. Animals were then assigned to control group,
      propofol (2 h, 0.7 mgkg(-1) min(-1)) group, surgery plus propofol group and
      surgery plus 1.5 MAC sevoflurane inhalation for 2h. Their hippocampal BBB
      permeability was detected with Evans blue quantification. Alterations of tight
      junctions in hippocampus were measured with occludin and claudin-5 western blot.
      Then we assessed matrix metalloproteinase-2,9 (MMP-2,9) via western blot and
      immunohistochemistry staining at day 1, 3, 7, and 14 after experiments. Surgery
      impaired cognitive function and increased Evans blue leakage into the hippocampus
      in aged rats while 2 h of 1.5 MAC sevoflurane inhalation potentiated these
      effects. Surgery induced occludin protein expression decreases and MMP-2,9
      proteins increase and these influences can be enhanced by high concentration of
      sevoflurane inhalation. In conclusion, 1.5 MAC sevoflurane for 2 h exacerbated
      cognitive impairment induced by orthopedic surgery in aged rats and the breach in
      BBB may be involved in this process.

PMID- 24440778
TI  - DNA directed immobilization glycocluster array: applications and perspectives.
AB  - The present review concerns the recent advances in DNA directed immobilization
      (DDI) based glycocluster array. The impact of glycan immobilization on subsequent
      interactions with protein is discussed and the consequent pros and cons of DDI
      based glycocluster array are reviewed. Finally, application in the discovery of
      anti-pathogen molecules is illustrated by screening for galactose or fucose
      glycoclusters targeting two Pseudomonas aeruginosa virulence factors (PA-IL and
      PA-IIL). 

PMID- 24440779
TI  - Neural basis of non-conscious visual working memory.
AB  - Recent research indicates that human observers can perform high-level cognitive
      tasks typically associated with working memory processes (e.g. learning of
      complex item sequences, reading, arithmetic or delayed visual discrimination)
      independently of conscious awareness of the relevant information. However, the
      neural basis of this phenomenon is not known. Here we show neuroimaging and
      neurostimulation evidence that the dorsolateral and anterior prefrontal cortex
      can operate on non-conscious information in a manner that goes beyond automatic
      forms of sensorimotor priming and which may support implicit working memory
      processes and higher-level cognitive function. 

PMID- 24440781
TI  - Sequence analysis of the equine ACTN3 gene in Australian horse breeds.
AB  - The sarcomeric alpha-actinins, encoded by the genes ACTN2 and ACTN3, are major
      structural components of the Z-line and have high sequence similarity. alpha
      Actinin-2 is present in all skeletal muscle fibres, while alpha-actinin-3 has
      developed specialized expression in only type 2 (fast, glycolytic) fibres. A
      common single nucleotide polymorphism (SNP) in the human ACTN3 gene (R577X) has
      been found to influence muscle performance in elite athletes and the normal
      population. For this reason, equine ACTN3 (eACTN3) is considered to be a possible
      candidate that may influence horse performance. In this study, the intron/exon
      boundaries and entire coding region of eACTN3 have been sequenced in five
      Australian horse breeds (Thoroughbred, Arabian, Standardbred, Clydsdale and
      Shire) and compared to the eACTN3 GenBank sequence. A total of 34 SNPs were
      identified, of which 26 were intronic and eight exonic. All exonic SNPs were
      synonymous; however, five intronic SNPs showed significant differences between
      breeds. A total of 72 horses were genotyped for a SNP located in the promoter
      region of the eACTN3 gene (g. 1104 G>A) which differed significantly between
      breed groups. We hypothesize that this polymorphism influences eACTN3 expression
      and with further studies may provide a novel marker of horse performance in the
      future.

PMID- 24440780
TI  - Localized diffusion magnetic resonance micro-imaging of the live mouse brain.
AB  - High-resolution diffusion MRI (dMRI) is useful for resolving complex
      microstructures in the mouse brain, but technically challenging for in vivo
      studies due to the long scan time. In this study, selective excitation and a
      three-dimensional fast imaging sequence were used to achieve in vivo high
      resolution dMRI of the mouse brain at 11.7Tesla. By reducing the field of view
      using spatially selective radio frequency pulses, we were able to focus on
      targeted brain structures and acquire high angular resolution diffusion imaging
      (HARDI) data at an isotropic resolution of 0.1mm and 30 diffusion encoding
      directions in approximately 1h. We investigated the complex tissue
      microstructures of the mouse hippocampus, cerebellum, and several cortical areas
      using this localized dMRI approach, and compared the results with histological
      sections stained with several axonal and dendritic markers. In the mouse visual
      cortex, the results showed predominately radially arranged structures in an outer
      layer and tangentially arranged structures in an inner layer, similar to
      observations from postmortem human brain specimens. 

PMID- 24440783
TI  - Association of functional FEN1 genetic variants and haplotypes and breast cancer
      risk.
AB  - AIM: As a tumor suppressor, FEN1 plays an essential role in preventing
      tumorigenesis. Two functional germline variants (-69G>A and 4150G>T) in the FEN1
      gene have been associated with DNA damage levels in coke-oven workers and
      multiple cancer risk in general populations. However, it is still unknown how
      these genetic variants are involved in breast cancer susceptibility. METHODS: We
      investigated the association between these polymorphisms and breast cancer risk
      in two independent case-control sets consisted of a total of 1100 breast cancer
      cases and 1400 controls. The influence of these variations on FEN1 expression was
      also examined using breast normal tissues. RESULTS: It was found that the FEN1
      69GG genotypes were significantly correlated to increased risk for developing
      breast cancer compared with the -69AA genotype in both sets [Jinan set: odds
      ratios (OR)=1.41, 95% confidence interval (CI)=1.20-1.65, P=1.9*10(-5); Huaian
      set: OR=1.51, 95% CI=1.22-1.86, P=1.7*10(-4)]. Similar results were observed for
      4150G>T polymorphism. The genotype-phenotype correlation analyses demonstrated
      that the -69G or 4150G allele carriers had more than 2-fold decreased FEN1
      expression in breast tissues compared with -69A or 4150T carriers, suggesting
      that lower FEN1 expression may lead to higher risk for malignant transformation
      of breast cells. CONCLUSION: Our findings highlight FEN1 as an important gene in
      human breast carcinogenesis and genetic variants in FEN1 confer susceptibility to
      breast cancer.

PMID- 24440784
TI  - Loeys-Dietz syndrome type 4, caused by chromothripsis, involving the TGFB2 gene.
AB  - The TGF-beta signaling pathway controls cellular proliferation, growth and
      differentiation and regulates several functions of the connective tissue.
      Disruption of genes coding for components of the TGF-beta signaling pathway or
      its interactors, such as fibrillin-1, has been shown to cause several human
      pathologies. Large deletions and non-sense mutations in TGFB2 gene have been
      recently described in patients with aortic aneurysm, scoliosis, arachnodactyly,
      chest deformities, joint hyper-flexibility, and mild intellectual disability;
      this condition has been called Loeys-Dietz syndrome, type 4. In this paper we
      describe an 18-year-old girl with borderline mental impairment, seizures, retinal
      degeneration, short stature, congenital hip dysplasia, severe and worsening joint
      hypermobility, scoliosis, progressive deformation of the long bones, aortic
      dilatation and platelet disorder. Molecular study of DNA by Array-CGH
      demonstrated four de novo microdeletions: TGFB2 is among the genes deleted and we
      consider it the obvious candidate for the clinical phenotype. The multiple
      chromosomal rearrangements detected in the current patient can be ascribed to an
      event of constitutional chromothripsis. 

PMID- 24440782
TI  - Stratified control of IGF-I expression by hypoxia and stress hormones in
      osteoblasts.
AB  - Bone cells respond to the integrated effects of local and systemic regulation.
      Here we show that hypoxia and the stress hormones PGE2 and glucocorticoid
      interact in complex ways in osteoblasts, converging on insulin like growth factor
      I (IGF-I) expression. Whereas hypoxia alone rapidly increased transcription
      factor HIF activity, it suppressed DNA synthesis, had no significant effects on
      protein synthesis or alkaline phosphatase activity, and drove discrete changes in
      a panel of osteoblast mRNAs. Notably, hypoxia increased expression of the acute
      phase response transcription factor C/EBPdelta which can induce IGF-I in response
      to PGE2, but conversely prevented the stimulatory effect of PGE2 on IGF-I mRNA.
      However, unlike its effect on C/EBPdelta, hypoxia suppressed expression of the
      obligate osteoblast transcription factor Runx2, which can activate an upstream
      response element in the IGF-I gene promoter. Hypoxic inhibition of IGF-I and
      Runx2 were enforced by glucocorticoid, and continued with prolonged exposure. Our
      studies thus reveal that IGF-I expression is stratified by two critical
      transcriptional elements in osteoblasts, which are resolved by the individual and
      combined effects of hypoxic stress and stress hormones. In so doing, hypoxia
      suppresses Runx2, limits the enhancing influence of PGE2, and interacts with
      glucocorticoid to reduce IGF-I expression by osteoblasts. 

PMID- 24440785
TI  - Identification and functional analysis of a novel mutation in the SOX10 gene
      associated with Waardenburg syndrome type IV.
AB  - Waardenburg syndrome type IV (WS4) is a rare genetic disorder, characterized by
      auditory-pigmentary abnormalities and Hirschsprung disease. Mutations of the
      EDNRB gene, EDN3 gene, or SOX10 gene are responsible for WS4. In the present
      study, we reported a case of a Chinese patient with clinical features of WS4. In
      addition, the three genes mentioned above were sequenced in order to identify
      whether mutations are responsible for the case. We revealed a novel nonsense
      mutation, c.1063C>T (p.Q355*), in the last coding exon of SOX10. The same
      mutation was not found in three unaffected family members or 100 unrelated
      controls. Then, the function and mechanism of the mutation were investigated in
      vitro. We found both wild-type (WT) and mutant SOX10 p.Q355* were detected at the
      expected size and their expression levels are equivalent. The mutant protein also
      localized in the nucleus and retained the DNA-binding activity as WT counterpart;
      however, it lost its transactivation capability on the MITF promoter and acted as
      a dominant-negative repressor impairing function of the WT SOX10.

PMID- 24440786
TI  - APOBEC2 mRNA and protein is predominantly expressed in skeletal and cardiac
      muscles of chickens.
AB  - Apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) plays an
      important role in regulating and maintaining muscle development in mammals. In
      this study, we evaluated APOBEC2 mRNA abundance and protein expression and the
      results indicated that APOBEC2 mRNA was most abundant in skeletal and cardiac
      muscle, with relatively low expression in the gonads, gizzard and subcutaneous
      fat tissues of chickens. Immunoreactive APOBEC2 was localized to the cell nucleus
      of developing myocardium and skeletal myofibers. There were significant
      differences in mRNA and protein abundance among ages, tissues, and between males
      and females. In conclusion, APOBEC2 was expressed as the greatest in skeletal
      muscle and cardiac muscle where it localized to the nucleus. Thus, APOBEC2 may
      play an important role in muscle development in chickens. 

PMID- 24440787
TI  - Homology of the mesopallium in the adult chicken identified by gene expression of
      the neocortical marker cholecystokinin.
AB  - Studies of gene expression and fiber connections have suggested that the primary
      visual (entopallium) and auditory (field L2) centers in the avian telencephalon
      are homologous to layer 4 of extrastriate and auditory neocortices of mammals,
      respectively. In addition, it has been proposed that the arcopallium contains
      neurons homologous to layers 5/6 and that the mesopallium may be homologous to
      superficial neocortical layers, but gene expression evidence for the latter is
      lacking in adult birds. In the present study using adult chickens we have
      examined the gene expression of cholecystokinin (CCK) mRNA, a selective marker
      for layers 2/3 of mammalian neocortex. CCK mRNA was expressed in neurons of the
      entire mesopallium, but not in any part of the nidopallium. Together with
      hodological evidence of connections between the mesopallium and the two primary
      sensory areas, our results are consistent with the suggestion that the
      mesopallium is comparable to certain superficial layers of mammalian neocortex. 

PMID- 24440788
TI  - Improved vascular survival and growth in the mouse model of hindlimb ischemia by
      a remote signaling mechanism.
AB  - Deficiencies in prolyl hydroxylase domain proteins (PHDs) may lead to the
      accumulation of hypoxia-inducible factor-alpha proteins, the latter of which
      activate local angiogenic responses by paracrine mechanisms. Here, we investigate
      whether a keratinocyte-specific PHD deficiency may promote vascular survival and
      growth in a distantly located ischemic tissue by a remote signaling mechanism. We
      generated mice that carry a keratinocyte-specific Phd2 knockout (kPhd2KO) and
      performed femoral artery ligation. Relative to wild-type controls, kPhd2KO mice
      displayed improved vascular survival and arteriogenesis in ischemic hind limbs,
      leading to the accelerated recovery of hindlimb perfusion and superior muscle
      regeneration. Similar protective effects were also seen in type 1 and type 2
      diabetic mice. Molecularly, both abundance of hypoxia-inducible factor-1alpha
      protein and expression of vascular endothelial growth factor-A were increased in
      epidermal tissues of kPhd2KO mice, accompanied by increased plasma concentration
      of vascular endothelial growth factor-A. Contrary to kPhd2KO mice, which are PHD2
      deficient in all skin tissues, localized kPhd2KO in hindlimb skin tissues did not
      have similar effects, excluding paracrine signaling as a major mechanism.
      Confirming the existence of remote effects, hepatocyte-specific Phd2 knockout
      also protected hind limbs from ischemia injury. These data indicate that vascular
      survival and growth in ischemia-injured tissue may be stimulated by suppressing
      PHD2 in a remotely located tissue and may provide highly effective angiogenesis
      therapies without the need for directly accessing target tissues. 

PMID- 24440790
TI  - Resuscitation highlights in 2013: Part 1.

PMID- 24440791
TI  - Resuscitation highlights in 2013: part 2.

PMID- 24440789
TI  - Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and
      humans.
AB  - Following acetaminophen (APAP) overdose there is an inflammatory response
      triggered by the release of cellular contents from necrotic hepatocytes into the
      systemic circulation which initiates the recruitment of neutrophils into the
      liver. It has been demonstrated that neutrophils do not contribute to APAP
      induced liver injury, but their role and the role of NADPH oxidase in injury
      resolution are controversial. C57BL/6 mice were subjected to APAP overdose and
      neutrophil activation status was determined during liver injury and liver
      regeneration. Additionally, human APAP overdose patients (ALT: >800 U/L) had
      serial blood draws during the injury and recovery phases for the determination of
      neutrophil activation. Neutrophils in the peripheral blood of mice showed an
      increasing activation status (CD11b expression and ROS priming) during and after
      the peak of injury but returned to baseline levels prior to complete injury
      resolution. Hepatic sequestered neutrophils showed an increased and sustained
      CD11b expression, but no ROS priming was observed. Confirming that NADPH oxidase
      is not critical to injury resolution, gp91(phox)-/- mice following APAP overdose
      displayed no alteration in injury resolution. Peripheral blood from APAP overdose
      patients also showed increased neutrophil activation status after the peak of
      liver injury and remained elevated until discharge from the hospital. In mice and
      humans, markers of activation, like ROS priming, were increased and sustained
      well after active liver injury had subsided. The similar findings between
      surviving patients and mice indicate that neutrophil activation may be a critical
      event for host defense or injury resolution following APAP overdose, but not a
      contributing factor to APAP-induced injury.

PMID- 24440792
TI  - Capnography as insight into etiology: a case of cardiac arrest following aortic
      rupture.

PMID- 24440793
TI  - Social supply of alcohol to Korean high school students: a cross-sectional
      International Alcohol Control Study.
AB  - PURPOSE: Underage drinking is strictly prohibited by law, nevertheless,
      adolescents report having access through social supply from family, friends and
      other members of the society. The aim of this study was to determine the primary
      suppliers of alcohol to Korean teenagers. DESIGN: Cross-sectional study. SETTING:
      Data were collected from 21 high schools in geographically diverse regions in
      South Korea from June to July 2012 as part of the International Alcohol Control
      Study. PARTICIPANTS: Data were analysed from 247 high schoolers aged 16-18 years
      old as part of the International Alcohol Control Study. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Social supply to high school students. RESULTS: More than 56%
      of high schoolers who participated in the International Alcohol Control Survey
      had been supplied alcohol at least once. Of this number, approximately 59% were
      males. Parents (especially fathers) and friends were the main suppliers, with
      friends contributing greater volumes (205 g) of alcohol. Of the number of
      students provided by mothers, 52% of them were females while 73% of respondents
      provided by friends were males. The most significant place for alcohol supply was
      at special events. Males were at higher odds for risky drinking. CONCLUSIONS:
      These results support previous findings about the role of parents and friends in
      underage drinking in South Korean high school drinkers.

PMID- 24440794
TI  - Changes in the rates of weight and waist circumference gain in Australian adults
      over time: a longitudinal cohort study.
AB  - OBJECTIVE: To assess in a single cohort whether annual weight and waist
      circumference (WC) change has varied over time. DESIGN: Longitudinal cohort study
      with three surveys (1) 1999/2000; (2) 2004/2005 and (3) 2011/2012. Generalised
      linear mixed models with random effects were used to compare annualised weight
      and WC change between surveys 1 and 2 (period 1) with that between surveys 2 and
      3 (period 2). Models were adjusted for age to analyse changes with time rather
      than age. Models were additionally adjusted for sex, education status, area-level
      socioeconomic disadvantage, ethnicity, body mass index, diabetes status and
      smoking status. SETTING: The Australian Diabetes, Obesity and Lifestyle study
      (AusDiab)-a population-based, stratified-cluster survey of 11247 adults aged >=25
      years. PARTICIPANTS: 3351 Australian adults who attended each of three surveys
      and had complete measures of weight, WC and covariates. PRIMARY OUTCOME MEASURES:
      Weight and WC were measured at each survey. Change in weight and WC was
      annualised for comparison between the two periods. RESULTS: Mean weight and WC
      increased in both periods (0.34 kg/year, 0.43 cm/year period 1; 0.13 kg/year,
      0.46 cm/year period 2). Annualised weight gain in period 2 was 0.11 kg/year (95%
      CI 0.06 to 0.15) less than period 1. Lesser annual weight gain between the two
      periods was not seen for those with greatest area-level socioeconomic
      disadvantage, or in men over the age of 55. In contrast, the annualised WC
      increase in period 2 was greater than period 1 (0.07 cm/year, 95% CI 0.01 to
      0.12). The increase was greatest in men aged 55+ years and those with a greater
      area-level socioeconomic disadvantage. CONCLUSIONS: Between 2004/2005 and
      2011/2012, Australian adults in a national study continued to gain weight, but
      more slowly than 1999/2000-2004/2005. While weight gain may be slowing, this was
      not observed for older men or those in more disadvantaged groups, and the same
      cannot be said for WC.

PMID- 24440795
TI  - Salt intake assessed by 24 h urinary sodium excretion in a random and
      opportunistic sample in Australia.
AB  - OBJECTIVE: The gold standard method for measuring population sodium intake is
      based on a 24 h urine collection carried out in a random population sample.
      However, because participant burden is high, response rates are typically low
      with less than one in four agreeing to provide specimens. At this low level of
      response it is possible that simply asking for volunteers would produce the same
      results. SETTING: Lithgow, New South Wales, Australia. PARTICIPANTS: We randomly
      selected 2152 adults and obtained usable 24 h urine samples from 306 (response
      rate 16%). Specimens were also collected from a further 113 volunteers. Estimated
      salt consumption and the costs for each strategy were compared. RESULTS: The
      characteristics of the 'random' and 'volunteer' samples were moderately different
      in mean age 58 (SD 14.6 vs 49(17.7) years, respectively; p<0.001) as well as self
      reported alcohol use, tobacco use, history of hypertension and prescription drug
      use (all p<0.04). Overall crude mean 24 h urinary salt excretion was 8.9(3.6)
      g/day in the random sample vs 8.5(3.3) g/day for the volunteers (p=0.42).
      Corresponding age-adjusted and sex-adjusted estimates were 9.2(3.3) and 8.8(3.4)
      g/day (p=0.29). Estimates for men 10.3(3.8) vs 9.6(3.3) g/day; (p=0.26) and women
      7.6(3) vs 7.9(3.2) g/day; (p=0.43) were also similar for the two samples, as was
      salt excretion across age groups (p=0.72). The cost of obtaining each 24 h urine
      sample was two times greater for the random compared to volunteer samples ($A62
      vs $A31). CONCLUSIONS: The estimated salt consumption derived from the two
      samples was comparable and was not substantively different to estimates obtained
      from other surveys. In countries where salt is pervasive and cannot easily be
      avoided, estimates of consumption obtained from volunteer samples may be valid
      and less costly.

PMID- 24440796
TI  - Patient- and surgeon-adjusted control charts for monitoring performance.
AB  - OBJECTIVES: To determine whether an innovative graphical tool for accurate
      measurement of individual surgeon performance metrics, adjusted for both surgeon
      specific and patient-specific factors, significantly alters interpretation of
      performance data. DESIGN: Retrospective analysis of all total knee replacements
      (TKRs) conducted at the host institution between 1996 and 2009. The database was
      randomly divided into training and testing datasets. Using multivariate
      generalised estimating equation regression models, the training dataset enabled
      generation of patient-risk and surgeon-experience adjustment factors. To simulate
      prospective monitoring of individual surgeon outcomes, the testing dataset was
      mapped on control charts. Weighted kappa statistics were calculated to measure
      the agreement between patient-risk adjusted and fully adjusted control charts.
      SETTING: Tertiary care academic hospital. PARTICIPANTS: All patients undergoing
      TKR at the host institution 1996-2009. MAIN OUTCOME MEASURE: Operative
      efficiency. RESULTS: 5313 procedures were analysed. Adjusted control charts were
      generated using a training dataset comprising 3756 procedures performed by 13
      surgeons. The operative time gradually declined by 121 min with 25 years of
      experience (p<0.0001). Charts were tested by monitoring four other surgeons,
      performing an average of 389 procedures each. Adjustment for surgeon experience
      significantly altered the interpretation of operative efficiency (kappa=0.29 (95%
      CI 0.11 to 0.47)), and enhanced assessment of a surgeon's improvement or
      diminishment in efficiency over time. Specifically, experience adjustment
      inverted the interpretation of surgeon efficiency from above average to below
      average, or from improving to declining performance. CONCLUSIONS: Adjustment for
      surgeon experience is necessary for accurate interpretation of metrics over the
      course of a surgeon's career. Patient-adjusted and surgeon-adjusted control
      charts provide an accurate method of monitoring individual operative efficiency.

PMID- 24440797
TI  - Fat & fabulous: bifunctional lipids in the spotlight.
AB  - Understanding biological processes at the mechanistic level requires a systematic
      charting of the physical and functional links between all cellular components.
      While protein-protein and protein-nucleic acid networks have been subject to many
      global surveys, other critical cellular components such as membrane lipids have
      rarely been studied in large-scale interaction screens. Here, we review the
      development of photoactivatable and clickable lipid analogues-so-called
      bifunctional lipids-as novel chemical tools that enable a global profiling of
      lipid-protein interactions in biological membranes. Recent studies indicate that
      bifunctional lipids hold great promise in systematic efforts to dissect the
      elaborate crosstalk between proteins and lipids in live cells and organisms. This
      article is part of a Special Issue entitled Tools to study lipid functions. 

PMID- 24440798
TI  - LC-ESI-MS/MS determination of simotinib, a novel epidermal growth factor receptor
      tyrosine kinase inhibitor: application to a pharmacokinetic study.
AB  - Simotinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor.
      This study presented a sensitive and specific liquid chromatography-electrospray
      ionization-mass spectrometry method using erlotinib as internal standard for the
      determination of simotinib in human plasma. The method involved a simple liquid
      liquid extraction using diethyl ether. The analytes were separated with isocratic
      gradient elution on an Agilent TC-C18 column (4.6 * 150 mm, 5 MUm). Mass
      spectrometric detector equipped with electrospray ionization source was carried
      out in the mode of multiple reaction monitoring (MRM). The monitored transitions
      were m/z 501.2->182.1 for simotinib and m/z 394.4->278.1 for erlotinib. The
      calibration curve of simotinib was established over the range of 2.058-3000 MUg
      L(-1) (r(2)=0.9924). The intra- and inter-day precisions were all less than 10%,
      and all the biases were not more than 7%. This validated method was then
      successfully applied to a pharmacokinetic study involving twelve healthy Chinese
      volunteers. The mean Cmax and Tmax for simotinib were 254.79+/-98.30 MUg L(-1)
      and 1.71+/-0.48 h, respectively. Plasma concentrations declined with a t1/2 of
      5.37+/-2.32 h. AUC0-t and AUC0->infinity values obtained were 1262.59+/-501.41
      MUg L(-1) h and 1329.95+/-517.42 MUg L(-1) h, respectively.

PMID- 24440799
TI  - An integrated expanded bed adsorption process for lactoferrin and immunoglobulin
      G purification from crude sweet whey.
AB  - An integrated expanded bed adsorption process was developed in this study to
      purify lactoferrin and immunoglobulin G (IgG) from crude sweet whey. The process
      used two sequential expanded beds packed with a cationic exchanger (Fastline SP)
      and a mixed-mode resin (Streamline Direct CST-1), respectively. Lactoferrin was
      isolated in the first expanded bed packed with Fastline SP, and the flow through
      was loaded into the second expanded bed packed with Streamline Direct CST-1 to
      separate IgG. Three integration strategies were compared to improve the
      separation efficiency, especially for the purification of IgG in the second
      expanded bed. The purities of IgG obtained from these three strategies were
      91.9%, 83.8% and 92.4%, and the recoveries were 14.3%, 63.7% and 29.7%,
      respectively. By efficient integration of the two expanded beds, lactoferrin and
      IgG were successfully recovered from crude sweet whey with high purities and
      reasonable recoveries. Moreover, the stream flowed out of the integrated process
      was collected and separated by ultrafiltration to produce whey protein
      concentrate. Therefore, sweet whey resource could be fully utilized. The results
      demonstrated that it is possible to purify multiple proteins from untreated crude
      resource with a rationally designed expanded bed adsorption process. 

PMID- 24440800
TI  - Levels of dechloranes and polybrominated diphenyl ethers (PBDEs) in human serum
      from France.
AB  - Human exposure to dechloranes has been evaluated in Western Europe (France) with
      the analysis of Dechlorane Plus (DP), Dechloranes (Dec) 602, 603 and 604,
      Chlordene Plus (CP) and Mirex in 48 serum samples collected between 2003 and
      2005. While no production source has been identified in Europe until now,
      detection frequencies for all investigated dechloranes were high, except for Dec
      604 which was below detection limit for all samples. The mean DP concentration
      was 1.40+/-1.40ng/g lipid weight (lw), lower than levels reported in serum from
      Chinese population, but higher than levels reported in Canadian human milk. To
      the best of our knowledge, this is the first time that ?5dechlorane levels are
      reported for human serum. A specific pattern of contamination was found (Dec
      603>DP>Mirex>Dec 602>CP) compared to other biota samples that have been analyzed
      from Europe, with Dec 603 as the most abundant dechlorane (mean level: 2.61+/
      2.63ng/g lw). Dec 603 and CP levels were correlated with age and with levels of
      some bioaccumulative organochlorine pesticides (OCPs). These results indicate
      that bioaccumulation properties should be further investigated and taken in
      consideration when assessing human exposure to dechloranes. For comparison
      purposes, polybrominated diphenyl ether (PBDE) levels were also measured for BDE
      47, -99, -100, -153 and -154 in the serum samples. As expected, BDE-47 and BDE
      153 were the major congeners with mean levels of 2.06+/-1.80ng/g lw and 1.39+/
      0.97ng/g lw, respectively. The mean ?5PBDE levels (4.32+/-2.99ng/g lw) were in
      the range typical of Western Europe levels, but lower than the mean ?5dechlorane
      levels (6.24+/-4.16ng/g lw). These results indicate that the attention to
      dechloranes should be continued if research indicates toxicological concerns. 

PMID- 24440801
TI  - A risk-based methodology for ranking environmental chemical stressors at the
      regional scale.
AB  - A "Risk-based Tool for the Regional Ranking of Environmental Chemical Stressors"
      has been developed, aimed at supporting decision-makers in the identification of
      priority environmental contaminants, as well as priority areas, to be further
      assessed. The tool implements a methodology based on a quantitative Weight-of
      Evidence approach, integrating three types of information, identified as "Lines
      of-Evidence" (LoE), namely: LoE "Environmental Contamination" (including data on
      chemical contamination in environmental matrices in the region, thus providing
      information on potential population exposure), LoE "Intake" (including results
      from human biomonitoring studies, i.e. concentration of chemicals in human
      biological matrices, thus providing an integrated estimation of exposure) and LoE
      "Observed Effects" (including information on the incidence of adverse health
      outcomes associated with environmental exposure to chemicals). A Multi-Criteria
      Decision Analysis (MCDA) methodology based on fuzzy logic has been developed to
      support the integration of information related to these three LoEs for each
      chemical stressor. The tool allows one to rank chemical stressors at different
      spatial scales, such as at the regional level as well as within each sub-area
      (e.g., counties). Moreover, it supports the identification of priority sub-areas
      within the region, where environmental and health data suggest possible adverse
      health effects and thus more investigation efforts are needed. To evaluate the
      performance of this newly developed tool, a case-study in the Flemish region
      (north of Belgium) has been selected. In the case-study, data on soil
      contamination by metals and organic contaminants were integrated with data on
      exposure and effect biomarkers measured in adolescents within the framework of
      the human biomonitoring study performed by the Flemish Centre of Expertise on
      Environment and Health in the period 2002-2006. The case-study demonstrated the
      performance of the tool in integrating qualitative and quantitative data with
      expert judgement for the identification of priority contaminants and areas. The
      proposed approach proved to be flexible, allowing for the incorporation of
      individual decision-maker's preferences, and, at the same time, to be transparent
      since all assumptions and value attributions are traceable. 

PMID- 24440802
TI  - The response of mouse embryonic stem cells to low doses of gamma-radiation:
      evidence for an adaptive response.
AB  - Low doses of ionizing radiation may induce an adaptive mechanism which protects
      embryonic stem cells against higher doses, a phenomenon which was reported
      previously for somatic cells. In this study, a possible adaptive response (AR)
      was evaluated by measuring cell survival (MTT assay) and chromosomal aberrations
      (micronucleus assay). Thymidine-synchronized mouse embryonic stem cells (mESCs)
      were exposed to 2.5, 3.7, or 5cGy (60)Co gamma-rays and, after 5h challenged by a
      dose of 150cGy. mESCs pre-irradiated at 2.5cGy showed an adaptive response. 

PMID- 24440803
TI  - Response to the letter of Bodgi and Foray: on the coherence between mathematical
      models of DSB repair and physiological reality.

PMID- 24440804
TI  - Anishinabe youth perceptions about community health: toward environmental
      repossession.
AB  - This community-based research applied environmental dispossession as a
      theoretical framework for understanding Anishinabe youth perceptions about
      health, social relationships and contemporary Anishinabe way of life in Northern
      Ontario, Canada. Qualitative interviews with 19 youth reveal considerable worry
      about their community's health. Youth perceive changes in the Anishinabe way of
      life, including decreased access to their traditional lands, to be central to
      poor health at the community level. Youth emphasized the importance of social
      relationships for fostering healthy behaviours and developing community wide
      initiatives that will provide opportunities for reconnecting to land, and for
      learning and practicing Indigenous Knowledge. This study builds on the growing
      body of decolonizing research with Indigenous communities, and it concludes by
      offering the concept of environmental repossession as a way forward for studies
      on the Indigenous environment-health interface. 

PMID- 24440805
TI  - Skin derived precursor Schwann cells improve behavioral recovery for acute and
      delayed nerve repair.
AB  - Previous work has shown that infusion of skin-derived precursors pre
      differentiated into Schwann cells (SKP-SCs) can remyelinate injured and
      regenerating axons, and improve indices of axonal regeneration and
      electrophysiological parameters in rodents. We hypothesized that SKP-SC therapy
      would improve behavioral outcomes following nerve injury repair and tested this
      in a pre-clinical trial in 90 rats. A model of sciatic nerve injury and acellular
      graft repair was used to compare injected SKP-SCs to nerve-derived Schwann cells
      or media, and each was compared to the gold standard nerve isograft repair. In a
      second experiment, rats underwent right tibial nerve transection and received
      either acute or delayed direct nerve repair, with injections of either 1) SKP-SCs
      distal to the repair site, 2) carrier medium alone, or 3) dead SKP-SCs, and were
      followed for 4, 8 or 17weeks. For delayed repairs, both transected nerve ends
      were capped and repaired 11weeks later, along with injections of cells or media
      as above, and followed for 9 additional weeks (total of 20weeks). Rats were
      serially tested for skilled locomotion and a slip ratio was calculated for the
      horizontal ladder-rung and tapered beam tasks. Immediately after nerve injury and
      with chronic denervation, slip ratios were dramatically elevated. In the GRAFT
      repair study, the SKP-SC treated rats showed statistically significant
      improvement in ladder rung as compared to all other groups, and exhibited the
      greatest similarity to the sham controls on the tapered beam by study
      termination. In the ACUTE repair arm, the SKP-SC group showed marked improvement
      in ladder rung slip ratio as early as 5weeks after surgery, which was sustained
      for the duration of the experiment. Groups that received media and dead SKP-SCs
      improved with significantly slower progression. In the DELAYED repair arm, the
      SKP-SC group became significantly better than other groups 7weeks after the
      repair, while the media and the dead SKP-SCs showed no significant improvement in
      slip ratios. On histomorphometrical analysis, SKP-SC group showed significantly
      increased mean axon counts while the percent myelin debris was significantly
      lower at both 4 and 8weeks, suggesting that a less inhibitory micro-environment
      may have contributed to accelerated axonal regeneration. For delayed repair, mean
      axon counts were significantly higher in the SKP-SC group. Compound action
      potential amplitudes and muscle weights were also improved by cell therapy. In
      conclusion, SKP-SC therapy improves behavioral recovery after acute, chronic and
      nerve graft repair beyond the current standard of microsurgical nerve repair. 

PMID- 24440806
TI  - Identification of a meiosis-specific protein, MEIOB, as a novel cancer/testis
      antigen and its augmented expression in demethylated cancer cells.
AB  - Cancer/testis (CT) antigens, which are expressed in various cancer cells but not
      in normal cells except germline cells of the testis, have been used as targets
      for cancer vaccine therapy. 5-Aza-2'-deoxycytidine (DAC), a potent inhibitor of
      genomic and promoter-specific DNA methylation, inhibits DNA methyltransferase
      activity and is reported to induce the expression of certain CT antigens by the
      demethylation of promoter CpG islands of the treated cells. Here, using DAC
      treated cancer cells, we searched for novel attractive target molecules that
      would be useful for cancer immunotherapy and found a meiosis-specific protein,
      meiosis specific with OB domains (MEIOB), to be a novel CT antigen. Indeed, the
      MEIOB gene is expressed only in the testis and not in other normal tissues. The
      mRNA expression of MEIOB was greatly enhanced in several lung cancer cell lines
      after the treatment with DAC. Furthermore, we identified a variety of helper
      epitopes of the MEIOB antigen, which were recognized by MEIOB antigen-specific T
      cells in a HLA-restriction manner. Finally, we demonstrated that IFN-gamma
      production of MEIOB peptide-specific helper T cells in response to HLA-matched
      cancer cells was greatly augmented by treatment with DAC and IFN-gamma. Taken
      together, these findings show DAC to be a promising tool for finding novel CT
      antigens and for developing a future novel combination cancer vaccine
      chemotherapy. 

PMID- 24440807
TI  - Exacerbation of intestinal brush border enzyme activities and oxidative stress in
      streptozotocin-induced diabetic rats by monocrotophos.
AB  - The present study was undertaken to investigate the potential of monocrotophos
      (MCP), one of the widely used broad spectrum systemic organophosphorus
      insecticides (OPI) in India, to alter small intestinal structure and function.
      Further, its potential to exacerbate diabetes induced alterations in intestinal
      structure and function was also studied in experimentally induced diabetic rats.
      Rats were rendered diabetic with an acute dose of streptozotocin (60 mg/kg b.w.).
      MCP was orally administered at a sublethal dose (1/20 LD50 i.e. 0.9 mg/kg b.w./d)
      for 15 days to both normal and diabetic rats. MCP significantly increased unit
      weight of intestine in diabetic rats. MCP alone increased (up to 57%) the
      activities of intestinal brush border disaccharidases in normal rats and further
      augmented the enzyme activities in diabetic rats. Similar results were found with
      intestinal alkaline phosphatase activity. In addition, Na(+)/K(+)-ATPase activity
      was found to be aggravated in diabetic rats by MCP treatment. Oxidative stress
      markers showed similar degree of change in both MCP and diabetic rats while MCP
      aggravated oxidative stress condition in diabetic rats. Scanning electron
      microscopy and histological analysis of the small intestine revealed increased
      length of villi, congestion, goblet cell hyperplasia and infiltration of
      inflammatory cells in MCP and diabetic rats while MCP also induced necrotic
      lesions in diabetic rats. Collectively, our findings provide evidence that
      multiple doses of MCP has the propensity to augment diabetes associated
      intestinal dysfunctions in rats.

PMID- 24440808
TI  - Silibinin induces apoptosis of HT29 colon carcinoma cells through early growth
      response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1
      (NAG-1) up-regulation.
AB  - Silibinin, an effective anti-cancer and chemopreventive agent, has been shown to
      exert multiple effects on cancer cells, including inhibition of both cell
      proliferation and migration. However, the molecular mechanisms responsible for
      these effects are not fully understood. We observed that silibinin significantly
      induced the expression of the non-steroidal anti-inflammatory drug-activated gene
      1 (NAG-1) in both p53 wild-type and p53-null cancer cell lines, suggesting that
      silibinin-induced NAG-1 up-regulation is p53-independent manner. Silibinin up
      regulates early growth response-1 (EGR-1) expression. The ectopic expression of
      EGR-1 significantly increased NAG-1 promoter activity and NAG-1 protein
      expression in a dose-dependent manner. Furthermore, down-regulation of EGR-1
      expression using siRNA markedly reduced silibinin-mediated NAG-1 expression,
      suggesting that the expression of EGR-1 is critical for silibinin-induced NAG-1
      expression. We also observed that reactive oxygen species (ROS) are generated by
      silibinin; however, ROS did not affect silibinin-induced NAG-1 expression and
      apoptosis. In addition, we demonstrated that the mitogen-activated protein kinase
      (MAP kinase) signal transduction pathway is involved in silibinin-induced NAG-1
      expression. Inhibitors of p38 MAP kinase (SB203580) attenuated silibinin-induced
      NAG-1 expression. Furthermore, we found that siRNA-mediated knockdown of NAG-1
      attenuated silibinin-induced apoptosis. Collectively, the results of this study
      demonstrate for the first time that up-regulation of NAG-1 contributes to
      silibinin-induced apoptosis in cancer cells. 

PMID- 24440809
TI  - Ondansetron combined with ST36 (Zusanli) acupuncture point injection for
      postoperative vomiting.
AB  - BACKGROUND: Ondansetron, sometimes combined with acustimulation at PC6 (Neiguan),
      is commonly used for preventing postoperative nausea and vomiting, but PC6 is not
      the only point that can be used for this purpose. OBJECTIVES: To evaluate the
      combined effects of ondansetron and ST36 (Zusanli) acupuncture point injection on
      postoperative vomiting (POV) after laparoscopic surgery. METHODS: A randomised,
      patient and assessor-blinded, placebo-controlled clinical study was conducted.
      One hundred and sixty patients undergoing laparoscopic surgery were randomly
      assigned to one of four groups: (1) group P (placebo-control): intravenous normal
      saline+bilateral non-acupuncture point injection of vitamin B1 (n=40); (2) group
      O (ondansetron): intravenous ondansetron+bilateral ST36 sham injection (n=40);
      (3) group A (acupuncture point injection): intravenous normal saline+bilateral
      acupuncture point injection at ST36 of vitamin B1 (n=40); (4) group C
      (combination): intravenous ondansetron+bilateral acupuncture point injection at
      ST36 of vitamin B1 (n=40). Interventions were made on arrival at the
      postanaesthesia care unit. The primary outcome was the incidence of POV within 24
      h after the operation. Secondary outcomes included severity of vomiting,
      incidence of rescue treatment, patients' satisfaction and the first anal
      exsufflation time 24 h after the operation. RESULTS: The incidence of POV within
      24 h postoperative period in each group was P 33%; O 11%, A 9% and C 6%. Outcomes
      for all intervention groups were significantly better than that for placebo
      (p<0.01). For the three interventions compared with placebo, the numbers needed
      to treat (NNTs) were O, NNT=5; A, NNT=5 and C, NNT=4. The secondary outcomes also
      demonstrated greater benefits of the combined regimen, with improvement seen in
      all the measures. CONCLUSIONS: Ondansetron, acupuncture, and ondansetron and
      acupuncture combined are effective prophylaxis for POV.

PMID- 24440810
TI  - Calculation of crystalline lens power in chickens with a customized version of
      Bennett's equation.
AB  - This paper customizes Bennett's equation for calculating lens power in chicken
      eyes from refraction, keratometry and biometry. Previously published data on
      refraction, corneal power, anterior chamber depth, lens thickness, lens radii of
      curvature, axial length and eye power in chickens aged 10-90 days were used to
      estimate Gullstrand's lens power and Bennett's lens power for chicken eyes, and
      to calculate the lens equivalent refractive index. Bennett's A and B constants
      for the front and back surface powers of the lens were calculated for data
      measured from day 10 to 90 at 10 day intervals, and mean customized constants
      were calculated. The mean customized constants for Bennett's equation for chicks
      were A=0.574+/-0.023 and B=0.379+/-0.021. As found previously, lens power
      decreases with age in chicks, while corneal power decreases and axial length
      increases. The lens equivalent refractive index decreases with age from 10 to 90
      days after hatching. Bennett's equation can be used to calculate lens power in
      chicken eyes for studies on animal myopia, using standard biometry.

PMID- 24440811
TI  - Imagining sex and adapting to it: different aftereffects after perceiving versus
      imagining faces.
AB  - A prolonged exposure (i.e., perceptual adaptation) to a male or a female face can
      produce changes (i.e., aftereffects) in the subsequent gender attribution of a
      neutral or average face, so that it appears respectively more female or more
      male. Studies using imagery adaptation and its aftereffects have yielded
      conflicting results. In the present study we used an adaptation paradigm with
      both imagined and perceived faces as adaptors, and assessed the aftereffects in
      judged masculinity/femininity when viewing an androgynous test face. We monitored
      eye movements and pupillary responses as a way to confirm whether participants
      did actively engage in visual imagery. The results indicated that both perceptual
      and imagery adaptation produce aftereffects, but that they run in opposite
      directions: a contrast effect with perception (e.g., after visual exposure to a
      female face, the androgynous appears as more male) and an assimilation effect
      with imagery (e.g., after imaginative exposure to a female face, the androgynous
      face appears as more female). The pupillary responses revealed dilations
      consistent with increased cognitive effort during the imagery phase, suggesting
      that the assimilation aftereffect occurred in the presence of an active and
      effortful mental imagery process, as also witnessed by the pattern of eye
      movements recorded during the imagery adaptation phase. 

PMID- 24440812
TI  - Increased frequency of chromosomal aberrations and sister chromatid exchanges in
      peripheral lymphocytes of radiology technicians chronically exposed to low levels
      of ionizing radiations.
AB  - Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) frequencies
      were estimated in peripheral lymphocytes from 21 radiology technicians, and from
      21 non-exposed control subjects. We exclusively considered individuals who
      neither smoke nor consume drugs or alcohol for a period of at least two years
      prior to the analysis. Significant differences were found between exposed and
      controls in terms of SCEs and CAs frequencies. Technicians showed a significant
      higher number of high-frequency individuals (HFIs) with respect to the control
      group. Nevertheless, the mean frequency of SCEs observed among technician HFIs
      did not significantly differ with respect to that observed among control HFIs.
      Vice versa, the non-HFIs belonging to technicians group showed a statistically
      higher difference in the SCEs/NSM value with respect to the non-HFIs belonging to
      control group. Since the differences in the SCEs frequencies between the two
      groups are due to non-HFIs, our results seem to indicate a general genotoxic
      effect of the IR, not affected by HFIs. Among technicians, the level of
      chromosome damage correlated neither with years of radiation exposure nor with
      the age of the subjects. Vice versa, in the control group, a positive correlation
      was found between the number of SCEs and age. In both samples the gender status
      did not influence the frequencies of CAs and SCEs. Our results suggest that
      chronic long-term exposure to low doses of ionizing radiation could increase the
      CAs and SCEs frequencies. This study reinforces the relevance of the
      biomonitoring of hospital workers chronically exposed to ionizing radiation. 

PMID- 24440813
TI  - Is BoNT/B useful for pain treatment?

PMID- 24440814
TI  - Differential proteome and gene expression reveal response to carbon ion
      irradiation in pubertal mice testes.
AB  - Heavy ion radiation, a high linear energy transfer (LET) radiation, has been
      shown to have adverse effects on reproduction in male mice. The aim of this study
      was to profile and investigate the differentially expressed proteins in pubertal
      male mice testes following carbon ion radiation (CIR). Male mice underwent whole
      body irradiation with CIR (1 and 4 Gy), and MALDI-TOF/TOF analysis was used to
      investigate the alteration in protein expression in 2-DE (two-dimensional gel
      electrophoresis) gels of testes caused by irradiation after 14 days. 8
      differentially expressed proteins were identified and these proteins were mainly
      involved in energy supply, the endoplasmic reticulum, cell proliferation, cell
      cycle, antioxidant capacity and mitochondrial respiration, which play important
      roles in the inhibition of testicular function in response to CIR. Furthermore,
      we confirmed the relationship between transcription of mRNA and the abundance of
      proteins. Our results indicated that these proteins may lead to new insights into
      the molecular mechanism of CIR toxicity, and suggested that the gene expression
      response to CIR involves diverse regulatory mechanisms from transcription of mRNA
      to the formation of functional proteins.

PMID- 24440815
TI  - Assessment of genetic diversity among Indian potato (Solanum tuberosum L.)
      collection using microsatellite and retrotransposon based marker systems.
AB  - Potato (Solanum tuberosum) is an important non-cereal crop throughout the world
      and is highly recommended for ensuring global food security. Owing to the
      complexities in genetics and inheritance pattern of potato, the conventional
      method of cross breeding for developing improved varieties has been difficult.
      Identification and tagging of desirable traits with informative molecular markers
      would aid in the development of improved varieties. Insertional polymorphism of
      copia-like and gypsy-like long terminal repeat retrotransposons (RTN) were
      investigated among 47 potato varieties from India using Inter-Retrotransposon
      Amplified Polymorphism (IRAP) and Retrotransposon Microsatellite Amplified
      Polymorphism (REMAP) marker techniques and were compared with the DNA profiles
      obtained with simple sequence repeats (SSRs). The genetic polymorphism,
      efficiency of polymorphism and effectiveness of marker systems were evaluated to
      assess the extent of genetic diversity among Indian potato varieties. A total of
      139 polymorphic SSR alleles, 270 IRAP and 98 REMAP polymorphic bands, showing
      polymorphism of 100%, 87.9% and 68.5%, respectively, were used for detailed
      characterization of the genetic relationships among potato varieties by using
      cluster analysis and principal coordinate analysis (PCoA). IRAP analysis resulted
      in the highest number of polymorphic bands with an average of 15 polymorphic
      bands per assay unit when compared to the other two marker systems. Based on pair
      wise comparison, the genetic similarity was calculated using Dice similarity
      coefficient. The SSRs showed a wide range in genetic similarity values (0.485
      0.971) as compared to IRAP (0.69-0.911) and REMAP (0.713-0.947). A Mantel's
      matrix correspondence test showed a high positive correlation (r=0.6) between
      IRAP and REMAP, an intermediate value (r=0.58) for IRAP and SSR and the lowest
      value (r=0.17) for SSR and REMAP. Statistically significant cophenetic
      correlation coefficient values, of 0.961, 0.941 and 0.905 were observed for
      REMAP, IRAP and SSR, respectively. The widespread presence and distinct DNA
      profiles for copia-like and gypsy-like RTNs in the examined genotypes indicate
      that these elements are active in the genome and may have even contributed to the
      potato genome organization. Although the three marker systems were capable of
      distinguishing all the 47 varieties; high reproducibility, low cost and ease of
      DNA profiling data collection make IRAP and REMAP markers highly efficient whole
      genome scanning molecular probes for population genetic studies. Information
      obtained from the present study regarding the genetic association and
      distinctiveness provides an useful guide for selection of germplasm for plant
      breeding and conservation efforts. 

PMID- 24440816
TI  - Single acquisition of protelomerase gave rise to speciation of a large and
      diverse clade within the Agrobacterium/Rhizobium supercluster characterized by
      the presence of a linear chromid.
AB  - Linear chromosomes are atypical in bacteria and likely a secondary trait derived
      from ancestral circular molecules. Within the Rhizobiaceae family, whose genome
      contains at least two chromosomes, a particularity of Agrobacterium fabrum
      (formerly A. tumefaciens) secondary chromosome (chromid) is to be linear and
      hairpin-ended thanks to the TelA protelomerase. Linear topology and telA
      distributions within this bacterial family was screened by pulse field gel
      electrophoresis and PCR. In A. rubi, A. larrymoorei, Rhizobium skierniewicense,
      A. viscosum, Agrobacterium sp. NCPPB 1650, and every genomospecies of the biovar
      1/A. tumefaciens species complex (including R. pusense, A. radiobacter, A.
      fabrum, R. nepotum plus seven other unnamed genomospecies), linear chromid
      topologies were retrieved concomitantly with telA presence, whereas the remote
      species A. vitis, Allorhizobium undicola, Rhizobium rhizogenes and Ensifer
      meliloti harbored a circular chromid as well as no telA gene. Moreover, the telA
      phylogeny is congruent with that of recA used as a marker gene of the
      Agrobacterium phylogeny. Collectively, these findings strongly suggest that
      single acquisition of telA by an ancestor was the founding event of a large and
      diverse clade characterized by the presence of a linear chromid. This clade,
      characterized by unusual genome architecture, appears to be a relevant candidate
      to serve as a basis for a possible redefinition of the controversial
      Agrobacterium genus. In this respect, investigating telA in sequenced genomes
      allows to both ascertain the place of concerned strains into Agrobacterium spp.
      and their actual assignation to species/genomospecies in this genus. 

PMID- 24440817
TI  - Neuroprotective gases--fantasy or reality for clinical use?
AB  - The neuroprotective properties for certain medical gases have been observed for
      decades, leading to extensive research that has been widely reported and
      continues to garner interest. Common gases including oxygen, hydrogen, carbon
      dioxide and nitric oxide, volatile anesthetics such as isoflurane, sevoflurane,
      halothane, enflurane and desflurane, non-volatile anesthetics such as xenon and
      nitrous oxide, inert gases such as helium and argon, and even gases classically
      considered to be toxic (e.g., hydrogen sulfide and carbon monoxide) have all been
      supported by the evidence alluding to their use as potential neuroprotective
      agents. A wide range of neural injury types such as ischemic/hemorrhagic, stroke,
      subarachnoid hemorrhage, traumatic brain injury, perinatal hypoxic-ischemic brain
      injuries, neurodegenerative disease as well as spinal cord ischemia have been
      used as platforms for studying the neuroprotective effects of these gases, yet
      until now, none of the gases has been widely introduced into clinical use
      specifically for protection against neural injury. Insufficient clinical data
      together with contradictory paradigms and results further hinders the clinical
      trials. However, pre-clinical models suggest that despite the various classes of
      gases and the broad range of injuries to which medical gases confer, protection,
      several underlying mechanisms for their neuroprotective properties are similar.
      In this review, we summarize the literature concerning the neuroprotective effect
      of each gas and its underlying mechanisms, extract common targets reported for
      the neuroprotective effects of different gases, highlight the conflicting
      observations from clinical trials and further discuss the possible hindrances
      impeding clinical applications in order to propose future research perspectives
      and therapeutic exploitations. 

PMID- 24440818
TI  - TLR2/1 and sphingosine 1-phosphate modulate inflammation, myofibroblast
      differentiation and cell migration in fibroblasts.
AB  - Dermal fibroblasts are important regulators of inflammatory and immune responses
      in the skin. The aim of the present study was to elucidate the interaction
      between two key players in inflammation, Toll-like receptors (TLRs) and
      sphingosine 1-phosphate (S1P), in normal human fibroblasts in the context of
      inflammation, fibrosis and cell migration. We demonstrate that TLR2 ligation
      strongly enhances the production of the pro-inflammatory cytokines IL-6 and IL-8.
      S1P significantly induces pro-inflammatory cytokines time- and concentration
      dependently via S1P receptor (S1PR)2 and S1PR3. The TLR2/1 agonist Pam3CSK4 and
      S1P (>1MUM) or TGF-beta markedly upregulate IL-6 and IL-8 secretion. Pam3CSK4 and
      S1P alone promote myofibroblast differentiation as assessed by significant
      increases of alpha-smooth muscle actin and collagen I expression. Importantly,
      costimulation with S1P (>1MUM) induces differentiation into myofibroblasts. In
      contrast, Pam3CSK4 and low S1P concentrations (<1MUM) accelerate cell migration.
      These results suggest that TLR2/1 signaling and S1P cooperate in pro-inflammatory
      cytokine production and myofibroblast differentiation and promote cell migration
      of skin fibroblasts in a S1P-concentration dependent manner. Our findings provide
      significant insights into how infectious stimuli or danger signals and
      sphingolipids contribute to dermal inflammation which may be relevant for skin
      tissue repair after injury or disease. 

PMID- 24440819
TI  - Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A.
AB  - Adipose triglyceride lipase (ATGL) is required for efficient mobilization of
      triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore,
      ATGL strongly determines the availability of fatty acids for metabolic reactions.
      ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic
      hormones. These signals control enzyme expression and the interaction of ATGL
      with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether
      ATGL activity is also controlled by lipid intermediates generated during
      lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs
      in a non-competitive manner, similar as previously shown for hormone-sensitive
      lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose
      tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs,
      diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays
      revealed that acyl-CoAs do not disrupt the protein-protein interaction of ATGL
      and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of
      the presence of CGI-58 and occurs directly at the N-terminal patatin-like
      phospholipase domain of the enzyme. In conclusion, our results suggest that
      inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs
      could represent an effective feedback mechanism controlling lipolysis and
      protecting cells from lipotoxic concentrations of fatty acids and fatty acid
      derived lipid metabolites. 

PMID- 24440820
TI  - Choline kinase alpha expression during RA-induced neuronal differentiation: role
      of C/EBPbeta.
AB  - Neuronal differentiation is a complex process characterized by a halt in
      proliferation and extension of neurites from the cell body. This process is
      accompanied by changes in gene expression that mediate the redirection leading to
      neurite formation and function. Acceleration of membrane phospholipids synthesis
      is associated with neurite elongation, and phosphatidylcholine (PtdCho) is the
      major membrane phospholipid in mammalian cells. The transcription of two genes in
      particular encoding key enzymes in the CDP-choline pathway for PtdCho
      biosynthesis are stimulated; the Chka gene for choline kinase (CK) alpha isoform
      and the Pcyt1a gene for the CTP:phosphocholine cytidylyltransferase (CCT) alpha
      isoform. We report that the stimulation of CKalpha expression during retinoic
      acid (RA) induced differentiation depends on a promoter region that contains two
      CCAAT/Enhancer-binding Protein-beta (C/EBPbeta) sites. We demonstrate that during
      neuronal differentiation of Neuro-2a cells, RA induces Chka expression by a
      mechanism that involves ERK1/2 activation which triggers C/EBPbeta expression.
      Elevated levels of C/EBPbeta bind to the Chka proximal promoter (Box1) inducing
      CKalpha expression. In addition we identified a downstream sequence named Box2
      which together with Box1 is required for the promoter to reach the full
      induction. This is the first elucidation of the mechanism by which the expression
      of Chka is coordinately regulated during neuronal differentiation. 

PMID- 24440822
TI  - Impact of the presence and amount of myocardial fibrosis by cardiac magnetic
      resonance on arrhythmic outcome and sudden cardiac death in nonischemic dilated
      cardiomyopathy.
AB  - BACKGROUND: Current risk stratification for sudden cardiac death (SCD) in
      nonischemic dilated cardiomyopathy (NIDC) relies on left ventricular (LV)
      dysfunction, a poor marker of ventricular electrical instability. Contrast
      enhanced cardiac magnetic resonance has the ability to accurately identify and
      quantify ventricular myocardial fibrosis (late gadolinium enhancement [LGE]).
      OBJECTIVE: To evaluate the impact of the presence and amount of myocardial
      fibrosis on arrhythmogenic risk prediction in NIDC. METHODS: One hundred thirty
      seven consecutive patients with angiographically proven NIDC were enrolled for
      this study. All patients were followed up for a combined arrhythmic end point
      including sustained ventricular tachycardia (VT), appropriate implantable
      cardioverter-defibrillator (ICD) intervention, ventricular fibrillation (VF), and
      SCD. RESULTS: LV-LGE was identified in 76 (55.5%) patients. During a median
      follow-up of 3 years, the combined arrhythmic end point occurred in 22 (16.1%)
      patients: 8 (5.8%) sustained VT, 9 (6.6%) appropriate ICD intervention, either
      against VF (n = 5; 3.6%) or VT (n = 4; 2.9%), 3 (2.2%) aborted SCD, and 2 (1.5%)
      died suddenly. Kaplan-Meier analysis revealed a significant correlation between
      the LV-LGE presence (not the amount and distribution) and malignant arrhythmic
      events (P < .001). In univariate Cox regression analysis, LV-LGE (hazard ratio
      [HR] 4.17; 95% confidence interval [CI] 1.56-11.2; P = .005) and left bundle
      branch block (HR 2.43; 95% CI 1.01-5.41; P = .048) were found to be associated
      with arrhythmias. In multivariable analysis, the presence of LGE was the only
      independent predictor of arrhythmias (HR 3.8; 95% CI 1.3-10.4; P = .01).
      CONCLUSIONS: LV-LGE is a powerful and independent predictor of malignant
      arrhythmic prognosis, while its amount and distribution do not provide additional
      prognostic value. Contrast-enhanced cardiac magnetic resonance may contribute to
      identify candidates for ICD therapy not fulfilling the current criteria based on
      left ventricular ejection fraction.

PMID- 24440823
TI  - Quality control of Lonicera japonica stored for different months by electronic
      nose.
AB  - The objective of this study was to investigate the potential of the electronic
      nose (E-nose) technique for monitoring the storage time and quality of L.
      japonica. An E-nose was used to detect odors of L. japonica samples during a
      storage period of 16 months. Linear discriminant analysis (LDA) and radial basis
      function (RBF) neural network were performed to differentiate L. japonica samples
      stored for different months. The content of chlorogenic acid of L. japonica was
      determined to confirm the quality changes and investigate its correlation with
      the odor response values. Results showed that L. japonica samples of different
      storage months could be classified correctly by LDA and RBF neural network. The
      change trends of the odor response and the content of chlorogenic acid had both
      declined along with the storage time. Also, there was a significant correlation
      (p=0.000) between the odor index and the content of chlorogenic acid. In
      conclusion, the odor intensity could reflect the quality of L. japonica to a
      certain degree. The E-nose technique could be used as a rapid, simple, sensitive
      and effective method for the quality control of L. japonica. 

PMID- 24440824
TI  - Development of a validated UPLC method for simultaneous estimation of both free
      and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and
      cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats.
AB  - A sensitive ultra-performance liquid chromatography (UPLC) method was developed
      for simultaneous estimation of all-trans retinoic acid (ATRA) and cholecalciferol
      (vitamin D3) in rat plasma. The method was validated over the linear range of 1.0
      5000ng/ml (r(2)=0.999) for both vitamins with a limit of detection of 0.5ng/ml.
      Chromatographic separation was achieved using liquid-liquid extraction (LLE) on
      an Acquity BEH RP 18 column (2.1mm*50mm, I.D. 1.7MUm), with mobile phase
      comprising of acetonitrile:methanol:water (90:8:2, v/v/v), at a flow rate of
      0.20ml/min and a total run time of 5min. Intra and inter-day variability (RSD)
      was <=3.1%, and the accuracy varied between 95.4-99.9% and 95.3-101.1%
      respectively, for ATRA and 98.5-100.8% and 99.3-101.7%, respectively for vitamin
      D3. High recovery of >=96.0% for ATRA and >=87.80% for vitamin D3 was achieved.
      ATRA and vitamin D3 were stable in plasma under different storage and processing
      conditions. The method was applied to estimate the total drug content and
      entrapment efficiency of ATRA and vitamin D3 loaded solid lipid nanoparticles
      (SLNs). Concentration of these two agents was determined in rat plasma after
      simultaneous subcutaneous administration in free form or when loaded into SLNs
      thus establishing pharmacokinetic application of the developed procedure. Results
      indicated an improvement in AUC0-infinity by 5.4 times and 29.4 times for ATRA
      and vitamin D3, respectively, upon their incorporation into SLNs. Simultaneous
      administration of these two vitamins and their improved and prolonged
      bioavailability has scope for their use in treatment and control of tuberculosis.

PMID- 24440825
TI  - In silico robustness testing of a compendial HPLC purity method by using of a
      multidimensional design space build by chromatography modeling-Case study
      pramipexole.
AB  - Purity testing of the active pharmaceutical ingredient (API) pramipexole is
      performed using an official (compendial) and harmonized method published in the
      European Pharmacopeia (E.P.) and United States Pharmacopeia (USP). According to
      this monograph the successful chromatographic separation of the API from
      impurities is achieved on a C18 column with gradient elution of an ion pairing
      buffer of pH 3.0 (mobile phase A) and acetonitrile (mobile phase B). Although not
      recommended in general, compendial methods are often adapted for purity testing
      of generic formulations. In this paper a novel approach to evaluate method
      robustness of an adapted method - prior of full method validation - is described.
      Based on Quality-by-Design (QbD) principles, a small number of experiments are
      performed, which after entering them into a chromatography modeling software
      allow to visualize a multidimensional "Design Space", a region, in which changes
      in method parameters will not significantly affect the results as defined in the
      ICH guideline Q8(R2) leading to a more flexible method handling in routine
      analysis. For two different recommended C18 columns a multidimensional Design
      Space (Method Operating Design Region, MODR) was constructed to study the
      robustness of the adapted method with a newly developed Robustness Module. In a
      full factorial design the following six parameters were varied at three levels
      (low, nominal, high): gradient time, temperature, pH of the aqueous eluent (A),
      flow rate, start- and end concentration of the organic mobile phase component
      (eluent B). The resulting 3(6)=729 experiments were performed in silico from the
      previously constructed models for Design Space in less than 1min and showed that
      the required resolution of 2.0 could not be reached in all experiments for the
      two columns which were recommended by the E.P. (failure rate 25% and 16%,
      respectively). However, by adjusting the gradient time, we were able to fulfill
      the requirements with a failure rate of zero. For the aqueous eluent a separate
      "Eluent Design Space" study was performed, which allows the construction of ionic
      strength vs. ion pairing concentration models to identify the optimum combination
      of the concentrations for the buffer and the ion-pairing reagent. 

PMID- 24440826
TI  - Application of LA-ICP-MS as a rapid tool for analysis of elemental impurities in
      active pharmaceutical ingredients.
AB  - The control of inorganic contaminants in active pharmaceutical ingredients has a
      significant role in the quality control of drug products. The concentration
      limits for metal residues in drug products have been defined by various
      regulatory guidelines. Laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS) is a powerful and fast analytical technique for multi
      elemental analysis. A disadvantage in using LA-ICP-MS method is the lack of
      matrix reference materials for validation and calibration purposes. This article
      focuses on the handling strategy of laboratory-made matrix calibration standards
      for the quantification of elemental impurities in an active pharmaceutical
      ingredient by LA-ICP-MS. 

PMID- 24440827
TI  - AMPK-sensitive cellular transport.
AB  - The energy sensing AMP-activated protein kinase (AMPK) regulates cellular and
      whole-body energy balance through stimulating catabolic ATP-generating and
      suppressing anabolic ATP-consuming pathways thereby helping cells survive during
      energy depletion. The kinase has previously been reported to be either directly
      or indirectly involved in the regulation of several carriers, channels and pumps
      of high significance in cellular physiology. Thus AMPK provides a necessary link
      between cellular energy metabolism and cellular transport activity. Better
      understanding of the AMPK role in cellular transport offers a potential for
      improved therapies in various human diseases and disorders. In this review, we
      discuss recent advances in understanding the role and function of AMPK in
      transport regulation under physiological and pathological states. 

PMID- 24440828
TI  - De novo analysis of the Nilaparvata lugens (Stal) antenna transcriptome and
      expression patterns of olfactory genes.
AB  - We sequenced the antenna transcriptome of the brown planthopper (BPH),
      Nilaparvata lugens (Stal), a global rice pest, and performed transcriptome
      analysis on BPH antenna. We obtained about 40million 90bp reads that were
      assembled into 75,874 unigenes with a mean size of 456bp. Among the antenna
      transcripts, 32,856 (43%) showed significant similarity (E-value <1e(-5)) to
      known proteins in the NCBI database. Gene ontology and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) analyses were used to classify functions of BPH antenna
      genes. We identified 10 odorant-binding proteins (OBPs), including 7 previously
      unidentified, and 11 chemosensory proteins (CSPs), including two new members. The
      expression profiles of 4 OBPs and 2 CSPs were determined by q-PCR for antenna,
      abdomen, leg and wing of insects of different age, gender, and mating status
      including two BPH adult wing-morphology types. NlugCSP10 and 4 OBPs appeared to
      be antenna-specific because they were highly and differentially expressed in male
      and female antennae. NlugCSP11 was expressed ubiquitously, with particularly high
      expression in wings. The transcript levels of several olfactory genes depended on
      adult wing form, age, gender, and mating status, although no clear expression
      patterns were determined. 

PMID- 24440829
TI  - Agmatine attenuates nicotine induced conditioned place preference in mice through
      modulation of neuropeptide Y system.
AB  - The purpose of the present study was to examine the effect of agmatine on
      nicotine induced conditioned place preference (CPP) in male albino mice. Intra
      peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time
      spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered
      with nicotine during the 6 days conditioning sessions completely abolished the
      acquisition of nicotine-induced CPP in mice. Concomitant administration of
      neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse,
      icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of
      agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1
      receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine
      (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine
      decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of
      stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular
      nucleus (PVN). Conversely, administration of agmatine prior to the nicotine
      significantly reversed the effect of nicotine on NPY-immunoreactivity in the
      above brain nuclei. This data indicate that agmatine attenuate nicotine induced
      CPP via modulation of NPYergic neurotransmission in brain.

PMID- 24440830
TI  - Differential regulation of oxidative burst by distinct beta-glucan-binding
      receptors and signaling pathways in human peripheral blood mononuclear cells.
AB  - beta-Glucans possess broad immunomodulatory properties, including activation of
      innate immune functions such as oxidative burst activity. The differential roles
      of complement receptor type 3 (CR3) and Dectin-1, the known beta-glucan
      receptors, and their associated signaling pathways in the generation of oxidative
      burst induced by different physical forms of Saccharomyces cerevisiae-derived
      beta-glucan were examined in human peripheral blood mononuclear cells (PBMC). In
      this study whole glucan particle (WGP) or immobilized soluble beta-glucan (ISG)
      was used to represent the phagocytizable or the nonphagocytizable form of a
      fungus, respectively. Oxidative burst as measured by the formation of superoxide
      (SO) was detected in PBMC in response to WGP and ISG. SO induction with WGP was
      concluded to be Dectin-1-mediated and required Src family kinases,
      phosphatidylinositol-3 kinase and protein kinase B/Akt. In contrast, the SO
      induction generated by ISG was CR3-mediated and required focal adhesion kinase,
      spleen tyrosine kinase, phosphatidylinositol-3 kinase, Akt, p38 mitogen activated
      protein kinase, phospholipase C and protein kinase C. The study results support
      the hypothesis that human PBMC, specifically monocytes, utilize distinct
      receptors and overlapping, but distinct, signaling pathways for the oxidative
      burst in response to challenge by different physical forms of beta-glucan. 

PMID- 24440821
TI  - Chemical modulation of glycerolipid signaling and metabolic pathways.
AB  - Thirty years ago, glycerolipids captured the attention of biochemical researchers
      as novel cellular signaling entities. We now recognize that these biomolecules
      occupy signaling nodes critical to a number of physiological and pathological
      processes. Thus, glycerolipid-metabolizing enzymes present attractive targets for
      new therapies. A number of fields-ranging from neuroscience and cancer to
      diabetes and obesity-have elucidated the signaling properties of glycerolipids.
      The biochemical literature teems with newly emerging small molecule inhibitors
      capable of manipulating glycerolipid metabolism and signaling. This ever
      expanding pool of chemical modulators appears daunting to those interested in
      exploiting glycerolipid-signaling pathways in their model system of choice. This
      review distills the current body of literature surrounding glycerolipid
      metabolism into a more approachable format, facilitating the application of small
      molecule inhibitors to novel systems. This article is part of a Special Issue
      entitled Tools to study lipid functions. 

PMID- 24440831
TI  - Structural modifications of gold thin films produced by thiol-derivatized single
      stranded DNA immobilization.
AB  - Recent experiments have reported an opposite sign of the differential surface
      stress produced on gold-coated cantilevers by a thiol-derivatized single-stranded
      DNA (SH-DNA) immobilization process. The sign of the surface stress depends on
      the method used to evaporate the gold thin film, being compressive (negative) or
      tensile (positive) for e-beam or resistively deposited gold, respectively. This
      study investigates the origin of this effect by means of a combination of x-ray
      diffraction and x-ray photoelectron spectroscopy. Both e-beam and resistively
      grown gold thin films are characterized to find the subtle differences
      responsible for this intriguing stress behaviour. Somewhat remarkably, these
      studies show a tight relation between the surface structure of the gold overlayer
      and the SH-DNA immobilization efficiency. The average grain size variation seems
      to correlate well with the differential surface stress triggered by the SH-DNA
      immobilization previously reported. These results suggest that the relation of
      the probe molecules with the surface structure must be considered to understand
      surface stress changes. 

PMID- 24440832
TI  - Comparison of clinical outcomes of patients with clear cell and endometrioid
      ovarian cancer associated with endometriosis to papillary serous carcinoma of the
      ovary.
AB  - OBJECTIVE: The aim of this investigation was to compare outcomes of patients with
      clear cell carcinoma (CCC) and endometrioid carcinoma (EC) of the ovary
      associated with endometriosis to patients with ovarian papillary serous carcinoma
      (PSC). METHODS: Patients with CCC and EC of the ovary associated with
      endometriosis were identified and matched by age and stage to PSC controls.
      Student's t test and chi square test were used to analyze continuous and
      categorical data. The Kaplan-Meier method was used for survival analysis.
      RESULTS: 67 cases associated with endometriosis were identified, of which 45 were
      arising in endometriosis. Cases were matched to 134 PSC controls. 27 patients
      with tumors associated with endometriosis presented at stage I (40.3%), 27 at
      stage II (40.3%), ten at stage III (14.9%) and three at stage IV (4.5%). There
      was no difference in rate of optimal cytoreduction or response to chemotherapy in
      cases vs. PSC controls. There was a significant increase in synchronous
      endometrial cancer in tumors associated with endometriosis compared to PSC (25.4%
      vs. 3.7%; P<0.001). 18 cases (26.9%) had recurrent disease vs. 55 (41%) controls
      (P=0.03). The 5-year disease-free survival (DFS) and overall survival (OS) of
      patients with tumors associated with endometriosis compared to PSC controls were
      75% vs. 55% (P=0.03) and 85% vs. 77% (P=0.2), respectively. CONCLUSIONS: Patients
      with tumors associated with endometriosis had a higher rate of synchronous
      endometrial cancer. Cases also demonstrated a lower rate of recurrence and
      improved 5 year DFS; however, this did not translate into a difference in OS.

PMID- 24440833
TI  - Lymph-node metastasis in stage I and II sex cord stromal and malignant germ cell
      tumours of the ovary: a systematic review.
AB  - OBJECTIVES: The aim of this systematic review is to determine the incidence of
      lymph-node metastasis in clinical stage I and II sex cord stromal tumours and
      germ cell tumours of the ovary. METHODS: Relevant articles were identified from
      MEDLINE and EMBASE and supplemented with citations from the reference lists of
      the primary studies. Eligibility was determined by two authors. Included studies
      were prospective or retrospective cohort and cross-sectional studies analysing at
      least ten patients with clinical early-stage non-epithelial ovarian cancer who
      underwent lymphadenectomy or lymph-node sampling as part of a staging laparotomy.
      RESULTS: For sex cord stromal tumours, five articles including 578 patients were
      analysed and lymph-node metastasis was not detected in the 86 patients who
      underwent lymph-node removal. The median number of removed lymph nodes was 13
      (range 9-29). For malignant germ cell tumours, three articles were eligible
      including 2436 patients of whom 946 patients underwent lymph-node resection. The
      mean number of removed nodes was 10 (range 2-14) with a mean incidence of lymph
      node metastasis of 10.9% (range 10.5-11.8%). CONCLUSIONS: The incidence of lymph
      node metastasis in patients with clinical stage I and II sex cord stromal tumours
      is low, whereas the incidence in patients with clinical stage I-II germ cell
      tumours is considerable, although limited data are available.

PMID- 24440834
TI  - A 2,4-dichlorophenoxyacetic acid degradation plasmid pM7012 discloses
      distribution of an unclassified megaplasmid group across bacterial species.
AB  - Analysis of the complete nucleotide sequence of plasmid pM7012 from 2,4
      dichlorophenoxyacetic-acid (2,4-D)-degrading bacterium Burkholderia sp. M701
      revealed that the plasmid had 582 142 bp, with 541 putative protein-coding
      sequences and 39 putative tRNA genes for the transport of the standard 20 aa.
      pM7012 contains sequences homologous to the regions involved in conjugal transfer
      and plasmid maintenance found in plasmids byi_2p from Burkholderia sp. YI23 and
      pBVIE01 from Burkholderia sp. G4. No relaxase gene was found in any of these
      plasmids, although genes for a type IV secretion system and type IV coupling
      proteins were identified. Plasmids with no relaxase gene have been classified as
      non-mobile plasmids. However, nucleotide sequences with a high level of
      similarity to the genes for plasmid transfer, plasmid maintenance, 2,4-D
      degradation and arsenic resistance contained on pM7012 were also detected in
      eight other megaplasmids (~600 or 900 kb) found in seven Burkholderia strains and
      a strain of Cupriavidus, which were isolated as 2,4-D-degrading bacteria in Japan
      and the United States. These results suggested that the 2,4-D degradation
      megaplasmids related to pM7012 are mobile and distributed across various
      bacterial species worldwide, and that the plasmid group could be distinguished
      from known mobile plasmid groups. 

PMID- 24440835
TI  - OmpR phosphorylation regulates ompS1 expression by differentially controlling the
      use of promoters.
AB  - The Salmonella enterica ompS1 gene encodes a quiescent porin that belongs to the
      OmpC/OmpF family. In the present work we analysed the regulatory effects of OmpR
      phosphorylation on ompS1 expression. We found that in vivo, OmpR in its
      phosphorylated form (OmpR-P) was important in the regulation of the two ompS1
      promoters: OmpR-P activated the P1 promoter and repressed the P2 promoter in an
      EnvZ-dependent manner; expression occurs from the P2 promoter in an ompR mutant.
      In vitro, OmpR-P had a higher DNA-binding-affinity to the ompS1 promoter region
      than OmpR and OmpRD55A, showing an affinity even higher than that of equivalent
      DNA regions in the 5'-upstream regulatory sequence of the major porin-encoding
      genes ompC and ompF. By analysing different environmental conditions, we found
      that glucose and glycerol enhanced ompS1 expression in the wild-type strain.
      Interestingly the stimulation by glycerol was OmpR-dependent while the effect of
      glucose was still observed in the absence of OmpR. Acetyl phosphate produced by
      the AckA-Pta pathway did not influence ompS1 regulation. These data indicate the
      important role of the phosphorylation in the activity of OmpR on the differential
      regulation of both ompS1 promoters and its impact on the pathogenesis. 

PMID- 24440836
TI  - Elevated telomerase activity in essential thrombocythemia with extreme
      thrombocytosis.
AB  - INTRODUCTION: We performed a comparative analysis of telomerase activity (TA) in
      patients with myeloproliferative neoplasm (MPN) and myelodysplastic syndrome
      (MDS). The relationships between TA and known prognostic factors were also
      analyzed. MATERIALS AND METHODS: A telomeric repeat amplification protocol was
      performed with bone marrow hematopoietic cells from 96 normal controls, 44 MPNs,
      and 40 MDSs. RESULT: TA (measured as molecules/reaction) showed no correlation
      with age in the control group (R(2)=0.0057, p=0.464). MPN showed elevated TA
      compared with controls (15,537.57 vs. 7775.44, p=0.020). Patients with essential
      thrombocythemia showed markedly elevated TA (22,688.56, p=0.030), particularly in
      cases with extreme thrombocytosis versus those without extreme thrombocytosis
      (34,522.19 vs. 9375.71, p=0.041). MDS patients showed a TA value of 7578.50.
      CONCLUSION: There was no association between age and TA in bone marrow
      hematopoietic cells. TA was elevated in MPN but borderline in MDS, probably
      because of differences in the nature of the diseases. Elevated TA in patients
      with essential thrombocythemia, especially those with extreme thrombocytosis,
      suggests that an anti-telomerase strategy could be beneficial in the prevention
      of thrombotic complications.

PMID- 24440837
TI  - The correlation of the total antioxidant status (TAS), total oxidant status (TOS)
      and paraoxonase activity (PON1) with smoking.
AB  - OBJECTIVE: In this study, we aimed to assess the total antioxidant status (TAS),
      total oxidant status (TOS) and paraoxonase activity (PON1) in smokers and
      nonsmokers. DESIGN AND METHODS: This cross-sectional analytical study was
      conducted on 100 smokers and 100 nonsmokers. Low-density lipoprotein cholesterol
      (LDL-c), high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC),
      triglyceride (TG), fasting blood glucose (FBG), TAS, TOS and PON1 levels of the
      participants were determined in the blood samples. TAS and TOS were determined by
      using the automated measurement method. Paraoxon was used as a substrate for
      measuring PON1 activity. RESULTS: A statistically significant difference could
      not be found between smokers and nonsmokers in terms of mean FBG, LDL-c, HDL-c,
      TC, TG, TAS, TOS, PON1, oxidative stress index (OSI) and body mass index (BMI).
      Mean TAS and TOS levels were higher in men than women (p=0.001). As age (p=0.022)
      and age to start smoking (p=0.023) increased, TOS level decreased. As the age to
      start smoking (p=0.001) increased, TAS level decreased whereas as BMI (p=0.001)
      increased, TAS level also increased. A statistically significant relationship
      could not be established between age, age to start smoking, duration and amount
      of smoking, dependence score and BMI and PON1 (p>0.05). CONCLUSIONS: In our
      study, although no significant correlation could be established between smokers
      and nonsmokers in terms of mean TAS, TOS and PON1, it is a fact that TAS, TOS and
      PON1 in the organism are affected by many factors and therefore there is a need
      for more extensive studies in this regard.

PMID- 24440838
TI  - The distance discordance metric-a novel approach to quantifying spatial
      uncertainties in intra- and inter-patient deformable image registration.
AB  - Previous methods to estimate the inherent accuracy of deformable image
      registration (DIR) have typically been performed relative to a known ground
      truth, such as tracking of anatomic landmarks or known deformations in a physical
      or virtual phantom. In this study, we propose a new approach to estimate the
      spatial geometric uncertainty of DIR using statistical sampling techniques that
      can be applied to the resulting deformation vector fields (DVFs) for a given
      registration. The proposed DIR performance metric, the distance discordance
      metric (DDM), is based on the variability in the distance between corresponding
      voxels from different images, which are co-registered to the same voxel at
      location (X) in an arbitrarily chosen 'reference' image. The DDM value, at
      location (X) in the reference image, represents the mean dispersion between
      voxels, when these images are registered to other images in the image set. The
      method requires at least four registered images to estimate the uncertainty of
      the DIRs, both for inter- and intra-patient DIR. To validate the proposed method,
      we generated an image set by deforming a software phantom with known DVFs. The
      registration error was computed at each voxel in the 'reference' phantom and then
      compared to DDM, inverse consistency error (ICE), and transitivity error (TE)
      over the entire phantom. The DDM showed a higher Pearson correlation (Rp) with
      the actual error (Rp ranged from 0.6 to 0.9) in comparison with ICE and TE (Rp
      ranged from 0.2 to 0.8). In the resulting spatial DDM map, regions with distinct
      intensity gradients had a lower discordance and therefore, less variability
      relative to regions with uniform intensity. Subsequently, we applied DDM for
      intra-patient DIR in an image set of ten longitudinal computed tomography (CT)
      scans of one prostate cancer patient and for inter-patient DIR in an image set of
      ten planning CT scans of different head and neck cancer patients. For both intra-
      and inter-patient DIR, the spatial DDM map showed large variation over the volume
      of interest (the pelvis for the prostate patient and the head for the head and
      neck patients). The highest discordance was observed in the soft tissues, such as
      the brain, bladder, and rectum, due to higher variability in the registration.
      The smallest DDM values were observed in the bony structures in the pelvis and
      the base of the skull. The proposed metric, DDM, provides a quantitative tool to
      evaluate the performance of DIR when a set of images is available. Therefore, DDM
      can be used to estimate and visualize the uncertainty of intra- and/or inter
      patient DIR based on the variability of the registration rather than the absolute
      registration error. 

PMID- 24440839
TI  - Preparation and pharmaceutical evaluation of nano-fiber matrix supported drug
      delivery system using the solvent-based electrospinning method.
AB  - In this study, utilizing the solvent-based electrospinning (ES) method, which is
      mainly employed in the textile industry, we prepared nanofiber-based capsules
      including drugs for controlled-release delivery systems using methacrylic acid
      copolymer (EUDRAGIT((r)) S100, MAC) as a polymer, and evaluated their in vitro
      drug dissolution profiles and in vivo pharmacokinetics in rats. As the model
      drugs, uranine (UN) was used as a water-soluble drug and nifedipine (NP) as a
      water-insoluble drug. The mean diameters of drug free nano-fiber and nano-fiber
      including NP or UN were 751.5 +/- 67.2, 703.3 +/- 71.2 and 2477.8 +/- 206.1 nm,
      respectively. X-ray diffraction for the nano-fibrotic sheet showed that UN and/or
      NP were packed in nano-fiber in an amorphous form. The in vitro release of UN or
      NP from the nano-fiber packed capsules (NFPC) and milled-powder of nano-fiber
      packed capsules (MPPC) showed controlled release of UN or NP as compared to
      capsules of a physical mixture of MAC and each drug. An in vivo pharmacokinetic
      study in rats after intraduodenal administration of NFPC or MPPC including UN
      and/or NP clearly demonstrated that application of nano-fibrotic technique as a
      drug delivery system offers drastic changes in pharmacokinetic profiles for both
      water-soluble and water-insoluble drugs. The ES method is a useful technique to
      prepare a nano-fiber like solid dispersion for polar or nonpolar drugs, and has
      wide potential pharmaceutical applications.

PMID- 24440840
TI  - Racial differences in prescription of opioid analgesics for chronic noncancer
      pain in a national sample of veterans.
AB  - The purpose of this study was to investigate possible racial differences in
      opioid prescriptions among primary care patients with chronic noncancer pain
      receiving care in the Veterans Affairs health care system. This was a
      retrospective cohort study of 99,903 veterans with diagnoses of low back, neck,
      or joint pain selected to participate in the Veterans Affairs Survey of the
      Healthcare Experiences of Patients in fiscal year 2006. The outcome was
      prescription of opioids in the year following the first pain diagnosis, obtained
      through electronic medical record data. Analyses incorporated fixed effects for
      race, most recent pain intensity rating, new or established primary care patient
      status, and an interaction between race and most recent pain intensity rating,
      together with random effects for health care facility and race within facility.
      The association between patient race and prescription of opioids was moderated by
      baseline level of pain intensity scores (assessed on a 0-10 scale) and patient
      age. Among patients under 65 years of age, blacks with moderate (4-6) or high (7
      10) levels of pain were less likely to receive opioids than whites (P = .0025, P
      = .0011); however, there were no significant differences between black and white
      patients with low levels of pain intensity (1-3) and those with pain intensity
      ratings of 0 (no pain). Among patients 65 and older with pain intensity ratings
      of zero, blacks were more likely than whites to receive opioid prescriptions (P =
      .0087), but there were no significant racial differences in opioid prescriptions
      in those with low to high levels of pain. PERSPECTIVE: Among veterans under age
      65 reporting moderate to high levels of chronic noncancer pain, blacks were less
      likely to be prescribed opioids than whites, even after controlling for clinical
      and system-level factors. Results underscore the challenges of eliminating racial
      differences in pain treatment, despite comprehensive systemwide improvement
      initiatives.

PMID- 24440842
TI  - From the editor.

PMID- 24440843
TI  - Implementing managed care in an industrial rehabilitation program.
AB  - Managed care, with all its problems and potentials, is entering the scene in
      workers' compensation as a way to deal with escalating costs. Though the roots of
      managed care lie in cost containment efforts, its future depends on a shift in
      emphasis to quality of care. Clinicians must become partners with insurance
      companies and employers to evolve a "win-win" scenario that combines efficiency
      with effectiveness or risk both exclusion from provider networks and loss of
      control over what becomes incorporated into standards of care. Steps that can be
      taken by clinicians include developing a sense of accountability for final
      functional outcome, internal utilization management, and an internal case
      management protocol. 

PMID- 24440841
TI  - A multi-spectroscopic approach to investigate the interaction of prodigiosin with
      ct-DNA.
AB  - The interaction between prodigiosin (PG) and calf thymus DNA (ct-DNA) was
      investigated firstly by using UV-Visible (UV-Vis), fluorescence, Fourier
      transform infrared (FT-IR), circular dichroism (CD) spectroscopies and viscosity
      measurement in Tris-HCl buffer solution (pH 6.8). The experimental results
      indicated that PG intercalated into the DNA helix. Upon addition of ct-DNA, PG
      showed hypochromic effect and slight redshift in the absorption spectra, and the
      melting temperature of ct-DNA was increased by from 58 to 64 degrees C.
      Furthermore, FT-IR spectrum and CD spectra also suggested that the partial bases
      of ct-DNA react with prodigiosin. The fluorescence quenching mechanism was
      studied using ethidium bromide as a DNA probe, The binding constants of PG with
      ct-DNA in the presence of EB are 4.46*10(4) and 2.32*10(4)M(-1) at 298 and 310K,
      respectively, and the corresponding thermodynamic parameters DeltaG, DeltaH,
      DeltaS at various temperatures were obtained. 

PMID- 24440844
TI  - Factors influencing return to work for clients in a work-hardening center.
AB  - This pilot study investigated whether a simple statistical analysis of selected
      intake data in the charts of work-hardening clients could differentiate those
      clients who returned to work from those who did not. Data from 24 workers'
      compensation clients were examined. Perceived pain on initial evaluation was the
      only statistically significant variable (p<0.01). Lower pain levels correlated
      with a successful return to work. Statistical trends (p<0.10) suggested that a
      lower hourly wage, a higher occupational metabolic equivalent level, and a
      marital status of married or cohabitating correlated with a successful return to
      work. Data were used to describe a client at risk - one with high levels of pain,
      who was not in a physically demanding Job and lacked social support. Program
      recommendations were made to address these issues. It was concluded that as other
      work-hardening centers respond to the call for better outcome assessment, a
      similar design process could be used. 

PMID- 24440845
TI  - Attitudes and back belts in the workplace.
AB  - This study, conducted on hospital workers, investigated the influence of wearing
      back belts on employee job attitudes and the experience of back pain. Serial
      attitude surveys were administered to workers involved in a preventative program
      of education, exercise, and back belts. Attitudes were found to be significantly
      improved as a result of the back belt program. Employees perceived back belts as
      helping them avoid injury and reported a decreased experience of low back pain. 

PMID- 24440846
TI  - Reactivation of injured workers involved in a work-hardening program.
AB  - This study examined 94 injured workers (IWs) treated in a work-hardening program
      over an 18-month time span. Of the 94 subjects, 78 (82.98 %) were contacted by
      telephone 1 year after discharge from therapy. Data examined include demographic,
      therapeutic, and return-to-employment information. Discriminant analyses showed
      that 74 of the 94 IWs were not working while involved in work hardening. Of
      these, 70 IWs (94.59 %) were released to gainful employment on discharge. At the
      time of the follow-up call, 53 of the IWs (67.95 %) were still working. Of the 25
      IWs not working, 18 (69.23 %) were involved in litigation. The average subjective
      pain level for the nonworking group, on a 0-10 scale, was found to be twice that
      of the working group, 5.35 vs. 2.48 (p<.01). It was also discovered that 100 % of
      the IWs not working at follow up who were previously deemed noncompliant with
      work hardening were involved in a disputed claim. This study also found that
      noncompliant individuals were discharged from therapy much earlier than compliant
      subjects, after 5.5 versus 14.4 visits, and at a much lower cost, $798.39 versus
      $2,137.01. These results suggest that although "state-of-the-art" programming was
      administered, behavioral and psychosocial factors (compliance and litigation)
      confounded the reactivation outcome process. Implications for future research
      directions are discussed. 

PMID- 24440847
TI  - Putting job accommodation to work.
AB  - Job accommodation is an essential ingredient of employment for individuals with
      physical disabilities. Services such as supported employment have improved
      employment opportunities. However, rehabilitation practitioners encounter an
      increasingly varied and complex array of accommodation options from which to
      choose. This article describes the Job Accommodation System, a user-friendly tool
      that assists rehabilitation practitioners, employees, and employers to identify
      and implement job accommodations. 

PMID- 24440848
TI  - Energy costs of manual therapy: effects of plinth height and an assistive device.
AB  - The purpose of this investigation was to examine the metabolic and
      cardiopulmonary responses of an experienced therapist (8 years experience)
      performing manual therapy at standard (S) plinth height (31 in), elevated (E)
      plinth height (38 in), and standard (SMTH) and elevated (EMTH) plinth height
      wearing a manual therapy harness (MTH). The MTH, developed by one of the
      investigators (J.L.S.), is a vestlike device worn by the therapist, which, when
      attached to the patient, can be used to distract articular surfaces. The MTH
      allows the therapist more freedom of hand movement and use of body weight to help
      provide joint distraction. Inferior glide (Grade 3-Maitland) was provided to the
      lift hip of 12 individuals at a rate of 20 oscillations per minute for 4 minutes,
      continuously, so that steady-rate metabolic conditions could be established. Mean
      body mass and height for the 12 individuals was 70+/-10.5 kg and 174.5+/-13 cm,
      respectively. The therapist's heart rate returned to resting levels between each
      of the randomly assigned treatments. One subject was treated daily. The therapist
      (age 32) was chosen because of his clinical experience, similar height (172 em)
      and weight (73 kg) to the average adult American male, and excellent intra- and
      interday (5%<= METs, 5%<= HR) reproducibility. Metabolic equivalents (METs),
      heart rate (HR), and rate of perceived exertion (RPE) were measured and averaged
      for the last 2 minutes of each treatment condition. The therapist was unaware of
      day-to-day test results except for RPE. Mean METs were 3. 7,3.2,2.6, and 2.4 for
      S, E, SMTH, and EMTH, respectively. Mean HRs were .117, 110, 104, and 93
      beats/min for S, E, SMTH, and EMTH, respectively. RPE was 11. 0,8.7, 7.9, and
      7.3jorS, E, SMTH, and EMTH, respectively. Repeated-measures analysis of variance
      (Scheffe F-test) revealed that SMTH and EMTH METs were similar, and significantly
      different (p<=0.05) from Sand E. METs for E were significantly different and
      lower than for S. HRs were significantly greater during E than the SMTH
      condition. RPE for S was significantly greater than SMTH, E, or EMTH. It can be
      concluded that the MTH significantly reduced the physiologic cost of providing
      manual therapy at either standard or elevated plinth height. further studies on
      these types of assistive devices and the effects of health status of the
      therapist on the provision of manual therapy treatments at various plinth heights
      are needed. 

PMID- 24440849
TI  - Bench-marking effects in the blaming of professionals for incidents of aggression
      and assault.
AB  - This study compared all possible orders of responding to three vignettes
      describing incidents between a male patient and a female nurse in which the nurse
      is mildly assaulted, severely assaulted, or verbally abused by the patient (the
      control condition). Subjects were 32 female senior-year nursing students and 28
      practicing nurses. It was found that response levels to a given vignette could
      predict a respondent's response to the other vignettes. Also, a significant
      "bench-marking" effect was found: if a subject responded to the mild assault
      vignette first, the subject's overall response pattern best fit the general
      nonlinear assignment-of-blame pattern observed, but if the subject responded to
      the severe assault or control vignette first, this vignette set a bench mark for
      responding from which the subject's subsequent responses did not deviate greatly,
      which slightly distorted the subject's V-shaped nonlinear response pattern. 

PMID- 24440850
TI  - Communication: a marketing tool.
AB  - Good communication can be the most effective therapeutic and marketing tool used
      within an industrial rehabilitation program. Effective communication among
      professionals is a key way to establish and maintain an atmosphere of
      professional cohesiveness (Osborne and Courts, 1991). The benefits of good
      communication are numerous. Strong treatment planning, smooth transitions back to
      work, identifying symptom magnifiers, eliminating team splitting, and having new
      learning opportunities for professionals are among the benefits found most often
      in industrial rehabilitation (Brown, 1991). 

PMID- 24440851
TI  - Ergonomics certification update.
AB  - This article is an information update on issues in ergonomics. Ergonomic
      certification is currently being conducted by the Board of Certification in
      Professional Ergonomics. Ergonomic certification is also being discussed by
      health care professionals and has been addressed by the National
      Interdisciplinary Committee on Health Ergonomics. The activities of each
      organization are presented. 

PMID- 24440852
TI  - Tumor-induced perturbations of cytokines and immune cell networks.
AB  - Until recently, the intrinsically high level of cross-talk between immune cells,
      the complexity of immune cell development, and the pleiotropic nature of cytokine
      signaling have hampered progress in understanding the mechanisms of
      immunosuppression by which tumor cells circumvent native and adaptive immune
      responses. One technology that has helped to shed light on this complex signaling
      network is the cytokine antibody array, which facilitates simultaneous screening
      of dozens to hundreds of secreted signal proteins in complex biological samples.
      The combined applications of traditional methods of molecular and cell biology
      with the high-content, high-throughput screening capabilities of cytokine
      antibody arrays and other multiplexed immunoassays have revealed a complex
      mechanism that involves multiple cytokine signals contributed not just by tumor
      cells but by stromal cells and a wide spectrum of immune cell types. This review
      will summarize the interactions among cancerous and immune cell types, as well as
      the key cytokine signals that are required for tumors to survive immunoediting in
      a dormant state or to grow and spread by escaping it. Additionally, it will
      present examples of how probing secreted cell-cell signal networks in the tumor
      microenvironment (TME) with cytokine screens have contributed to our current
      understanding of these processes and discuss the implications of this
      understanding to antitumor therapies. 

PMID- 24440853
TI  - Real-time simulation of contact and cutting of heterogeneous soft-tissues.
AB  - This paper presents a numerical method for interactive (real-time) simulations,
      which considerably improves the accuracy of the response of heterogeneous soft
      tissue models undergoing contact, cutting and other topological changes. We
      provide an integrated methodology able to deal both with the ill-conditioning
      issues associated with material heterogeneities, contact boundary conditions
      which are one of the main sources of inaccuracies, and cutting which is one of
      the most challenging issues in interactive simulations. Our approach is based on
      an implicit time integration of a non-linear finite element model. To enable real
      time computations, we propose a new preconditioning technique, based on an
      asynchronous update at low frequency. The preconditioner is not only used to
      improve the computation of the deformation of the tissues, but also to simulate
      the contact response of homogeneous and heterogeneous bodies with the same
      accuracy. We also address the problem of cutting the heterogeneous structures and
      propose a method to update the preconditioner according to the topological
      modifications. Finally, we apply our approach to three challenging demonstrators:
      (i) a simulation of cataract surgery (ii) a simulation of laparoscopic
      hepatectomy (iii) a brain tumor surgery. 

PMID- 24440854
TI  - Stabilized Interleukin-6 receptor binding RNA aptamers.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine that is involved in the
      progression of various inflammatory diseases, such as rheumatoid arthritis and
      certain cancers; for example, multiple myeloma or hepatocellular carcinoma. To
      interfere with IL-6-dependent diseases, targeting IL-6 receptor (IL-6R)
      presenting tumor cells using aptamers might be a valuable strategy to broaden
      established IL-6- or IL-6R-directed treatment regimens. Recently, we reported on
      the in vitro selection of RNA aptamers binding to the human IL-6 receptor (IL-6R)
      with nanomolar affinity. One aptamer, namely AIR-3A, was 19 nt in size and able
      to deliver bulky cargos into IL-6R-presenting cells. As AIR-3A is a natural RNA
      molecule, its use for in vivo applications might be limited due to its
      susceptibility to ubiquitous ribonucleases. Aiming at more robust RNA aptamers
      targeting IL-6R, we now report on the generation of stabilized RNA aptamers for
      potential in vivo applications. The new 2'-F-modified RNA aptamers bind to IL-6R
      via its extracellular portion with low nanomolar affinity comparable to the
      previously identified unmodified counterpart. Aptamers do not interfere with the
      IL-6 receptor complex formation. The work described here represents one further
      step to potentially apply stabilized IL-6R-binding RNA aptamers in IL-6R
      connected diseases, like multiple myeloma and hepatocellular carcinoma. 

PMID- 24440855
TI  - Reduced cellular Ca(2+) availability enhances TDP-43 cleavage by apoptotic
      caspases.
AB  - Accumulation of transactive response DNA binding protein (TDP-43) fragments in
      motor neurons is a post mortem hallmark of different neurodegenerative diseases.
      TDP-43 fragments are the products of the apoptotic caspases-3 and -7. Either
      excessive or insufficient cellular Ca(2+) availability is associated with
      activation of apoptotic caspases. However, as far as we know, it is not described
      whether activation of caspases, due to restricted intracellular Ca(2+), affects
      TDP-43 cleavage. Here we show that in various cell lineages with restricted
      Ca(2+) availability, TDP-43 is initially cleaved by caspases-3 and -7 and then,
      also by caspases-6 and -8 once activated by caspase-3. Furthermore, we disclose
      the existence of a TDP-43 caspase-mediated fragment of 15kDa, in addition to the
      well-known fragments of 35 and 25kDa. Interestingly, with respect to the other
      two fragments this novel fragment is the major product of caspase activity on
      murine TDP-43 whereas in human cell lines the opposite occurs. This outcome
      should be considered when murine models are used to investigate TDP-43
      proteinopathies. 

PMID- 24440857
TI  - Confounding variables in neuromusculoskeletal function associated with self
      inflicted venous ulcer disease.

PMID- 24440856
TI  - GPI/AMF inhibition blocks the development of the metastatic phenotype of mature
      multi-cellular tumor spheroids.
AB  - Epithelial-mesenchymal transition (EMT) and cellular invasiveness are two pivotal
      processes for the development of metastatic tumor phenotypes. The metastatic
      profile of non-metastatic MCF-7 cells growing as multi-cellular tumor
      microspheroids (MCTSs) was analyzed by determining the contents of the EMT,
      invasive and migratory proteins, as well as their migration and invasiveness
      potential and capacity to secrete active cytokines such as the glucose phosphate
      isomerase/AMF (GPI/AMF). As for the control, the same analysis was also performed
      in MCF-7 and MDA-MB-231 (highly metastatic, MDA) monolayer cells, and in stage
      IIIB and IV human metastatic breast biopsies. The proliferative cell layers (PRL)
      of mature MCF-7 MCTSs, MDA monolayer cells and metastatic biopsies exhibited
      increased cellular contents (2-15 times) of EMT (beta-catenin, SNAIL), migratory
      (vimentin, cytokeratin, and fibronectin) and invasive (MMP-1, VEGF) proteins
      versus MCF-7 monolayer cells, quiescent cell layers of mature MCF-7 MCTS and non
      metastatic breast biopsies. The increase in metastatic proteins correlated with
      substantially elevated cellular abilities for migration (18-times) and
      invasiveness (13-times) and with the higher level (6-times) of the cytokine
      GPI/AMF in the extracellular medium of PRL, as compared to MCF-7 monolayer cells.
      Interestingly, the addition of the GPI/AMF inhibitors erythrose-4-phosphate or 6
      phosphogluconate at micromolar doses significantly decreased its extracellular
      activity (>80%), with a concomitant diminution in the metastatic protein content
      and migratory tumor cell capacity, and with no inhibitory effect on tumor lactate
      production or toxicity on 3T3 mouse fibroblasts. The present findings provide new
      insights into the discovery of metabolic inhibitors to be used as complementary
      therapy against metastatic and aggressive tumors.

PMID- 24440861
TI  - More 2014 procedure code changes for hospital-based outpatient wound care
      departments and ambulatory surgical centers.

PMID- 24440862
TI  - Pyoderma gangrenosum of the hand.
AB  - Pyoderma gangrenosum is a rare, painful, ulcerative neutrophilic dermatosis that
      is not usually seen on the hands. Pyoderma gangrenosum is a diagnosis of
      exclusion, as there are no specific laboratory or histopathologic findings to
      confirm the diagnosis. Heightened awareness and early recognition are needed to
      decrease morbidity in these patients. 

PMID- 24440863
TI  - The in vitro antimicrobial activity of wound and skin cleansers at nontoxic
      concentrations.
AB  - OBJECTIVE: To determine in vitro antibacterial activity of commercially available
      skin, wound, and skin/wound cleansers at cell-safe (nontoxic) concentrations.
      DESIGN: Saline and 19 other commercial wound and skin cleansers were evaluated
      for cytotoxic effects on mouse dermal fibroblasts. Cells were exposed to serial
      10-fold dilutions of each cleanser until treatment-induced cytotoxicity was
      comparable to the baseline cytotoxicity of unexposed control fibroblasts.
      Antimicrobial "time-kill" kinetics of these test concentrations of cleansers was
      tested against methicillin-resistant Staphylococcus aureus. RESULTS: The
      experimental design allowed calculation of relative cytotoxicity indexes ranging
      from 0 to 100,000. Shur-Clens Restore Wound Cleanser (ConvaTec, Skillman, New
      Jersey) and saline were found to be the least toxic (toxicity index: 0);
      Hibiclens (Molnlycke Health Care, Norcross, Georgia), Restore Skin Cleanser
      (Hollister Inc, Libertyville, Illinois), and Betadine Surgical Scrub (Pursue
      Products LP, Stamford, Connecticut) were found to be the most toxic (toxicity
      index: 10,000). At noncytotoxic concentrations, NeutroPhase (NovaBay
      Pharmaceuticals Inc, Emeryville, California) was the most rapidly bactericidal,
      achieving a 4-log reduction in colony-forming units in less than 1 minute.
      Puracyn (Innovacyn Inc, Rialto, California) was next at 30 minutes, whereas most
      of the agents tested required more than 24 hours. CONCLUSIONS: Wound healing
      depends on controlling bacterial balance while maintaining the viability of the
      healing tissues. In vitro toxicity indexes provide helpful guidelines subsequent
      to in vivo evaluations and clinical applications. The study findings suggest that
      NeutroPhase, in contrast with many commercially available wound cleansers, has
      rapid bactericidal activity at concentrations that are safe for human cells.

PMID- 24440864
TI  - Predictive validity of 4 risk assessment scales for prediction of pressure ulcer
      development in a hospital setting.
AB  - OBJECTIVES: The aims of this study were to examine and compare the predictive
      validity of 4 risk assessment scales used for the prediction of pressure ulcer
      (PrU) development and to identify risk factors. DESIGN: Cross-sectional
      descriptive study. SETTING: A general hospital in Sweden. PARTICIPANTS: Patients
      (all aged >=18 years) admitted to medical, surgical, orthopedic, oncology, and
      rehabilitation wards. Of 412 patients available, a total of 346 patients
      participated in the study. METHOD: Data were collected using the Swedish version
      of the European Pressure Ulcer Advisory Panel minimum data set as well as the
      Norton, Modified Norton, Braden, and Risk Assessment Pressure Sore (Ulcer) (RAPS)
      scales. The predictive validity was estimated by measuring sensitivity,
      specificity, positive predictive value, and negative predictive value. Multiple
      logistic regression analysis was used to determine risk factors associated with
      PrUs. RESULTS: The RAPS scale reached best balance between sensitivity and
      specificity at the recommended cutoff level of <=29, followed by the Braden scale
      and the Norton scale at recommended cutoff levels <=18 versus <=16, respectively.
      The modified Norton scale also reached an acceptable balance between sensitivity
      and specificity but at the cutoff level of <=23, which is a higher cutoff level
      than recommended. General physical condition, physical activity, moisture,
      friction, and shear emerged as significant risk factors. CONCLUSIONS: The results
      support that the recommended cutoff levels of the RAPS, Norton, and Braden scales
      are valid in a general hospital setting. However, the recommended cutoff level of
      the modified Norton scale (<=20) has to be increased when used in this care
      context.

PMID- 24440865
TI  - Negative-pressure therapy in the postoperative treatment of incisional
      hernioplasty wounds: a pilot study.
AB  - Negative pressure therapy has proven useful in the treatment of the complex
      complications of surgical wounds. In this pilot study, the authors found that the
      negative pressure system can be used safely in the postoperative period of
      incisional hernia surgery and reduces the number of days of drainage. 

PMID- 24440866
TI  - A comparative study of the five-times-sit-to-stand and timed-up-and-go tests as
      measures of functional mobility in persons with and without injection-related
      venous ulcers.
AB  - PURPOSE: To provide information on the Five-Times-Sit-to-Stand (FTSTS) and Timed
      Up-and-Go (TUG) tests in persons with injection-related venous ulcers (VU+) and
      persons without venous ulcers (VU-). TARGET AUDIENCE: This continuing education
      activity is intended for physicians and nurses with an interest in skin and wound
      care. OBJECTIVES: After participating in this educational activity, the
      participant should be better able to: ABSTRACT:  OBJECTIVE: To examine functional
      mobility using Five-Times-Sit-to-Stand (FTSTS) and Timed-Up-and-Go (TUG) tests in
      persons with injection-related venous ulcers (VU+) and compare these findings to
      persons without venous ulcers (VU-). DESIGN: Cross-sectional, comparative design.
      SETTING: Outpatient clinic.PARTICPANTS: Participants (n = 61) were 31 persons VU+
      and 30 persons VU-; 57.4% men; mean age, 54 years; 93% African American. MAIN
      OUTCOME MEASURES: Five-Times-Sit-to-Stand, TUG, physical activity, quality of
      life, comorbidities, falls, and body mass index. RESULTS: Participants VU+ were
      36.8% slower on completion of the TUG test (P = .012) and 26.5% slower on
      completion of the FTSTS test (P = .081). Five-Times-Sit-to-Stand and TUG were
      strongly correlated with each other, r = 0.93, 0.87, P < .001 for VU- and VU+,
      respectively. Test-retest reliabilities for the FTSTS and TUG tests were high
      (intraclass correlation coefficient = 0.89-0.94) for the VU+ and VU-. Within each
      group, correlations of FTSTS and TUG were similar for each of the variables
      examined. Across groups, correlations showed that the time to complete FTSTS and
      TUG increased as a function of comorbidities in the VU+ group; the correlations
      in the VU- group were not significantly different from zero. CONCLUSIONS: The VU+
      group exhibited poorer physical performance than the VU- group. The high
      correlation between FTSTS and TUG and the similarity of correlations with other
      variables suggest that these physical performance measures may be interchangeable
      in their ability to predict physical functioning in these clinical groups despite
      differences in test demands. Clinicians need easy-to-perform reliable clinical
      tests such as FTSTS and TUG to assess mobility of aging injection users with
      venous ulcers.

PMID- 24440868
TI  - 2014 OPPS final rule drives critical documentation elements.

PMID- 24440869
TI  - Chemical pathology reborn by the Bologna Process, syllabus mapping and
      accreditation.

PMID- 24440870
TI  - Cryopreservation of sperm in farmed Australian greenlip abalone Haliotis
      laevigata.
AB  - This study investigated factors important to the development of the liquid
      nitrogen (LN) vapor sperm cryopreservation technique in farmed greenlip abalone
      Haliotis laevigata, including (1) cryoprotectant agent (CPA) toxicity; (2)
      cooling temperature (height above LN surface); (3) thawing temperature; (4) sperm
      to egg ratio; and (5) sugar supplementation, using sperm motility, fertilization
      rate or integrity/potential of sperm components and organelles as quality
      assessment indicators. Results suggested that among the single CPAs evaluated 6%
      dimethyl sulfoxide (Me2SO) would be the most suitable for sperm cryopreservation
      in this species. The highest post-thaw sperm motility was achieved with the sperm
      that had been exposed to LN vapor for 10min at 5.2cm above the LN surface, thawed
      and recovered in 60 and 18 degrees C seawater bathes, respectively after at least
      2h storage in LN. The highest fertilization rates were achieved at a sperm to egg
      ratio of 10,000:1 or 15,000:1. Addition of 1% glucose or 2% sucrose produced
      significantly higher post-thaw sperm motility than 6% Me2SO alone. Among the
      three cryoprotectant solutions further trialled, 6% Me2SO+1% glucose produced the
      highest fertilization rate of 83.6+/-3.7%. Evaluation of sperm has shown that the
      addition of glucose could significantly improve the sperm plasma membrane
      integrity and mitochondrial membrane potential. These results demonstrated a
      positive role of glucose in the improvement of sperm cryopreservation in farmed
      greenlip abalone.

PMID- 24440871
TI  - Protective effects of propolis on cryopreservation of common carp (Cyprinus
      carpio) sperm.
AB  - Cryopreservation of sperm is common procedures in aquaculture, particularly used
      for routine in artificial insemination. However, these application cause damages
      and adversely affected sperm motility, viability and consequently lower hatching
      rates. The objective of this study is to determine whether propolis has an effect
      on cryopreservation and fertilization ability and to investigate the potential
      protective effect of propolis on spermatozoa of Cyprinus carpio. Many studies
      have been done in cryopreservation offish spermatozoa, but none of them contain
      propolis in extender composition. The extenders were prepared by using modified
      Kurokura Solution to which 10% Me(2)SO added with different levels of propolis
      (0.2, 0.4, 0.6, 0.8 and 1 mgml(-1)) and 10% egg yolk (as a control without
      propolis). The pooled semen samples diluted at the ratio of 1:9 by the extenders
      were subjected to cryopreservation. The percentage and duration of motility and
      fertilization tests of cryopreserved sperm samples have been done immediately
      after thawing and compared with control and fresh semen. The extenders containing
      propolis exhibited higher percentage motility and motility duration than control
      group (P < 0.05). Especially the group IV (0.8 mgml(-1) propolis) and the group V
      (1 mgml(-1) propolis) showed significant positive effects on both post thaw
      motility and hatching ability. The propolis maintained the integrity of the
      spermatozoa during the cryopreservation process. Evaluating with its contents, it
      has been shown that propolis is an appropriate cryoprotective agent in fish
      semen.

PMID- 24440872
TI  - Tolerance of apexes of coral Pocillopora damicornis L. to cryoprotectant
      solutions.
AB  - In this study, we investigated the tolerance of Pocillopora damicornis apexes to
      treatments with solutions containing penetrating and non-penetrating
      cryoprotective agents (CPAs). CPAs were employed individually or in binary,
      tertiary or quaternary solutions. In some experiments apexes were treated
      successively with two CPA solutions with increasing total concentration. P.
      damicornis apexes withstood exposure for up to 30 min to solutions containing 0.6
      0.8 M sucrose (Suc) or trehalose (Tre). When apexes were treated with binary
      cryoprotectant solutions containing Suc and ethylene glycol (EG), methanol
      (Meth), dimethyl sulfoxide (Me(2)SO) or glycerol (Gly), the CPAs employed in
      combination with Suc could be ranked in the following order of decreasing
      tolerance: EG>Meth>Me(2)SO>Gly. P. damicornis apexes tolerated exposure to
      complex CPA solutions containing Suc, Me(2)SO, EG and/or Meth with a total
      molarity of 2.45 M. In experiments where two successive CPA solutions were
      employed, apexes withstood treatment with the second, more concentrated solution
      at 0 degrees C for up to 10 min. These preliminary results pave the way to the
      development of a cryopreservation protocol for P. damicornis apexes.

PMID- 24440873
TI  - Selection of optimal reference genes for quantitative RT-PCR studies of boar
      spermatozoa cryopreservation.
AB  - Reference genes can be used to normalize mRNA levels across different samples for
      the exact comparison of the mRNA expression level. It is important to select
      reference genes with high quality for the accurate interpretation of qRT-PCR
      data. Although several studies have attempted to validate reference genes in
      pigs, no validation studies have been performed on spermatozoa samples frozen
      with different cryoprotectants. In this study, 11 commonly used reference genes
      (ACTB, B2M, GAPDH, HPRT1, RPL4, SDHA, YWHAZ, PPIA, PGK1, S18, and BLM) were
      investigated in boar spermatozoa frozen with six different cryoprotectants using
      qRT-PCR. The expression stability of these reference genes in different samples
      was evaluated using geNorm (qbase(plus) software), NormFinder, and BestKeeper.
      The geNorm results revealed that PGK1, ACTB, and RPL4 exhibit high expression
      stability in all of the samples, and the NormFinder results indicated that GAPDH
      is the most stable gene. Furthermore, the BestKeeper results indicated that the
      three most stable genes are PPIA, GAPDH, and RPL4 and that S18, B2M and BLM are
      the three least stable genes. There are a number of differences in the ranking
      order of the reference genes obtained using the different algorithms. In
      conclusion, GAPDH, RPL4, and PPIA were the three most stable genes in frozen boar
      spermatozoa, as determined based on the cycle threshold coefficient of variation
      (Ct CV%) and the comprehensive ranking order, and this finding is consistent with
      the BestKeeper results. 

PMID- 24440874
TI  - Chromatin remodeling mediated by the FOXA1/A2 transcription factors activates
      CFTR expression in intestinal epithelial cells.
AB  - The forkhead box A transcription factors, FOXA1 and FOXA2, function as pioneer
      factors to open condensed chromatin and facilitate binding of other proteins. We
      showed previously that these factors are key components of a transcriptional
      network that drives enhancer function at the cystic fibrosis transmembrane
      conductance regulator (CFTR) locus in intestinal epithelial cells. The CFTR
      promoter apparently lacks tissue-specific regulatory elements and expression of
      the gene is controlled by multiple cis-acting elements, which coordinate gene
      expression in different cell types. Here we show that concurrent depletion of
      FOXA1 and FOXA2 represses CFTR expression and alters the three-dimensional
      architecture of the active locus by diminishing interactions between the promoter
      and intronic cis-acting elements. Reduction of FOXA1/A2 also modifies the
      enrichment profile of the active enhancer marks H3K27ac and H3K4me2 across the
      CFTR locus and alters chromatin accessibility at individual cis-elements.
      Moreover, loss of FOXA1/A2 suppresses the recruitment of other members of the
      transcriptional network including HNF1 and CDX2, to multiple cis-elements. These
      data reveal a complex molecular mechanism underlying the role of FOXA1/A2 in
      achieving high levels of CFTR expression in intestinal epithelial cells. 

PMID- 24440875
TI  - Radiotherapy planning for glioblastoma based on a tumor growth model: improving
      target volume delineation.
AB  - Glioblastoma differ from many other tumors in the sense that they grow
      infiltratively into the brain tissue instead of forming a solid tumor mass with a
      defined boundary. Only the part of the tumor with high tumor cell density can be
      localized through imaging directly. In contrast, brain tissue infiltrated by
      tumor cells at low density appears normal on current imaging modalities. In
      current clinical practice, a uniform margin, typically two centimeters, is
      applied to account for microscopic spread of disease that is not directly
      assessable through imaging. The current treatment planning procedure can
      potentially be improved by accounting for the anisotropy of tumor growth, which
      arises from different factors: anatomical barriers such as the falx cerebri
      represent boundaries for migrating tumor cells. In addition, tumor cells
      primarily spread in white matter and infiltrate gray matter at lower rate. We
      investigate the use of a phenomenological tumor growth model for treatment
      planning. The model is based on the Fisher-Kolmogorov equation, which formalizes
      these growth characteristics and estimates the spatial distribution of tumor
      cells in normal appearing regions of the brain. The target volume for
      radiotherapy planning can be defined as an isoline of the simulated tumor cell
      density. This paper analyzes the model with respect to implications for target
      volume definition and identifies its most critical components. A retrospective
      study involving ten glioblastoma patients treated at our institution has been
      performed. To illustrate the main findings of the study, a detailed case study is
      presented for a glioblastoma located close to the falx. In this situation, the
      falx represents a boundary for migrating tumor cells, whereas the corpus callosum
      provides a route for the tumor to spread to the contralateral hemisphere. We
      further discuss the sensitivity of the model with respect to the input
      parameters. Correct segmentation of the brain appears to be the most crucial
      model input. We conclude that the tumor growth model provides a method to account
      for anisotropic growth patterns of glioma, and may therefore provide a tool to
      make target delineation more objective and automated. 

PMID- 24440877
TI  - EXAFS study of hydrogen intercalation into ReO 3 using the evolutionary
      algorithm.
AB  - In this study we have investigated the influence of hydrogen intercalation on the
      local atomic structure of rhenium trioxide using a new approach to EXAFS data
      analysis, based on the evolutionary algorithm (EA). The proposed EA-EXAFS method
      is an extension of the conventional reverse Monte Carlo approach but is
      computationally more efficient. It allows one to perform accurate analysis of
      EXAFS data from distant coordination shells, taking into account both multiple
      scattering and disorder (thermal and static) effects. The power of the EA-EXAFS
      method is first demonstrated on an example of the model system, pure ReO3, and
      then it is applied to an in situ study of hydrogen bronze HxReO3 upon hydrogen
      intercalation. The obtained results allow us to detect changes in the lattice
      dynamics and correlation of atomic motion, and to follow the structural
      development at different stages of the reaction. 

PMID- 24440876
TI  - Evidence for a crucial role of a host non-coding RNA in influenza A virus
      replication.
AB  - A growing body of evidence suggests the non-protein coding human genome is of
      vital importance for human cell function. Besides small RNAs, the diverse class
      of long non-coding RNAs (lncRNAs) recently came into focus. However, their
      relevance for infection, a major evolutionary driving force, remains elusive.
      Using two commercially available microarray systems, namely NCodeTM and
      SureprintTM G3, we identified differential expression of 42 ncRNAs during
      influenza A virus (IAV) infection in human lung epithelial cells. This included
      several classes of lncRNAs, including large intergenic ncRNAs (lincRNAs). As
      analyzed by qRT-PCR, expression of one lincRNA, which we termed virus inducible
      lincRNA (VIN), is induced by several IAV strains (H1N1, H3N2, H7N7) as well as
      vesicular stomatitis virus. However, we did not observe an induction of VIN by
      influenza B virus, treatment with RNA mimics, or IFNbeta. Thus, VIN expression
      seems to be a specific response to certain viral infections. RNA fractionation
      and RNA-FISH experiments revealed that VIN is localized to the host cell nucleus.
      Most importantly, we show that abolition of VIN by RNA interference restricts IAV
      replication and viral protein synthesis, highlighting the relevance of this
      lincRNA for productive IAV infection. Our observations suggest that viral
      pathogens interfere with the non-coding portion of the human genome, thereby
      guaranteeing their successful propagation, and that the expression of VIN
      correlates with their virulence. Consequently, our study provides a novel
      approach for understanding virus pathogenesis in greater detail, which will
      enable future design of new antiviral strategies targeting the host's non-protein
      coding genome. 

PMID- 24440879
TI  - From the editor.

PMID- 24440878
TI  - Japanese medaka exposed to gold nanoparticles: Only embryonic exposure generates
      irreversible hatching failure, developmental failure, and mortality of sac-fry.
AB  - This study evaluated irreversible toxicity effects of gold nanoparticles (AuNPs)
      during the short-term (only embryonic stage) and long-term (both embryo and sac
      fry stages) exposures of Japanese ricefish, Oryzias latipes (medaka) embryos and
      sac-fry. Embryos and sac-fry exposed to AuNPs at 8 and 15days post-fertilization
      exhibited mortality, developmental failure, and abnormal appearance, and sac-fry
      additionally exhibited hatching failure and abnormal behavior. Embryos damaged by
      AuNPs during the embryonic stages failed to hatch and died, despite being raised
      under AuNP-free conditions after embryonic exposure. This study demonstrates that
      AuNPs have irreversible effects on O. latipes embryos and sac-fry, including the
      embryonic stages, regardless of the length of exposure. This result may be
      critical for predicting the potential continuous effects of AuNPs when the
      exposure duration of fish is short but includes the embryonic stages. To the best
      of our knowledge, this is the first study to test the toxicity of AuNP exposure
      on the embryos and sac-fry of O. latipes. 

PMID- 24440880
TI  - Women and work.
AB  - An understanding of what work means to women is provided with an overview of
      history; a review of unpaid work, including child care, parental care, and
      volunteerism; and the current status of women and work. Women's leadership style
      emphasizing team building, empowerment, and a consensus model is described. The
      need for validation of the multiple roles women play in society and for espousing
      balance in their lives is encouraged. Finally, strategies for eliminating bias
      are offered. 

PMID- 24440881
TI  - Physical fitness and occupational performance of women in the u.s. Army.
AB  - The majority of jobs available to personnel entering the U.S. military services
      are physically demanding. Soldiers must maintain high levels of physical fitness
      to optimally perform their duties. High fitness levels are of particular
      importance to women in the military. Only strong, physically competent women will
      be fully successful in performing the physically demanding tasks of many
      occupational specialties. This paper describes the research that has been
      conducted to compare the physical fitness, physical training, and occupational
      performance of women and men in the U.S. Army. 

PMID- 24440882
TI  - Women's Socialization into Nontraditional Heavy WorkA Case Study.
AB  - An increasing number of opportunities are available for women in nontraditional,
      blue-collar work. However, for many women the lack of job skills, poor work
      conditions, differential treatment, shift work, and heavy physical labor deter
      them from entering or remaining in such jobs. This case study attempted to
      uncover workplace issues, the socialization process, and adaptive strategies for
      a female steel worker. Her strategies for survival included hard work, high work
      standards, "courteous but cool" relationships with coworkers, "standing up" for
      herself, and good friends or support systems. 

PMID- 24440883
TI  - From Private- to Public-Sector EmploymentLongitudinal Follow Up on Roles and
      Values of a Cohort Group.
AB  - In 1986 employees of a private rehabilitation service (n = 22) participated in a
      career development workshop given by the senior author. They completed the Life
      Roles Inventory (Fitzsimmons, Macnab, and Casserly, 1986), the Strong Vocational
      Interest Inventory (Strong, Campbell, and Hansen, 1981), and the Minnesota
      Satisfaction Questionnaire (Weiss, Dawis, England, et al., 1967). Participants
      documented the characteristics of their "ideal job" and the positive and negative
      aspects of their present positions. The results of this evaluation, along with
      their career path, were then reviewed with each participant on an individual
      basis. Economic factors later led to closure of the organization, and the
      employees were forced to find alternative employment. In 1990 the original
      participants agreed to participate in a follow-up study where they completed the
      same inventories and interview process. Results of this comparison indicated that
      in 1986 these individuals scored lower than the normative sample on the Life
      Roles Inventory Values Scales of Advancement, Aesthetics, Economics, and Working
      Conditions; in 1990 they only scored lower on Advancement. In addition, intrinsic
      satisfaction levels did not change substantially in 1990, but the level of
      extrinsic satisfaction was significantly lower. 

PMID- 24440884
TI  - Women: (not) the weaker sex at work?
AB  - Women's role has developed and changed dramatically in the last twenty years.
      Women now are prevalent in the work force and assuming work tasks not in their
      traditional pattern. Society and work injury managers are beginning to come to
      terms with women as a gender (different from men), women's specific strengths and
      weaknesses, and female oriented work injury problems. Science and logic blend to
      produce a clearer picture of women's physical parameters related to work. 

PMID- 24440885
TI  - Glass Ceilings and Lead BootsWomen's Self-Image in Therapy.
AB  - To provide the highest quality treatment to mature female clients, all aspects of
      the clients' roles, occupations, and health standards must be understood. By
      focusing on societal and cultural constructs and their deleterious effects on
      modern women, occupational therapists are better able to assess the obstacles to
      full functioning at home and in the workplace. There are many obstacles to women
      gaining full satisfaction from work and social roles, including legal restraints,
      inaccurate health standards, and destructive societal value systems. Progress and
      proper therapy can be realized by reviewing recent research in women's psychology
      and using the unique strengths of the occupational therapy profession. 

PMID- 24440886
TI  - An activity analysis of hand grips used in housework by female rheumatoid
      arthritics.
AB  - In this nonexperimental study, videofilmed, self-selected housework activities of
      rheumatic women were analyzed. The women gripped and manipulated objects in their
      homes. The activities were analyzed under the headings Activity, Actions,
      Objects, and Grip. The films were viewed frame by frame, and the data was
      computerized for statistical analysis. The women performed five self-selected
      housework activities and eight groups of actions (n = 340). During the actions
      the women handled 12 groups of objects using the eight grip classes of
      Sollerman's grip classification. The diagonal volar grip was the most common grip
      (20%), and the tripoid pinch was the least common (0.29%); 34% of the actions
      were right-handed, 19% left-handed, and 47% bimanual. No clear grip pattern was
      revealed by the activity analysis. 

PMID- 24440887
TI  - Disruption of Life Roles Following InjuryImpact on Women's Social Networks.
AB  - Clients with orthopedic and soft-tissue injuries (n = 53) who were settling
      insurance claims or currently in litigation were assessed using the Values
      Scales, Salience Inventory, measures of perceived exertion, physical capacity,
      and functional ability, and a structured interview, the Life Satisfaction
      Questionnaire. Participation in major life roles was compromised following
      injury. Role value scores for working and home/family roles also changed, but
      commitment to these roles did not. Women in this sample (n = 27) experienced
      disruptions in their social networks that were likely related to the compromise
      or loss of their working role. 

PMID- 24440889
TI  - Successful women.

PMID- 24440888
TI  - An Occupational Therapy Group Workshop for Patients with Osteoarthritis of
      HandsPreliminary Report.
AB  - Fourteen patients with osteoarthritis of the hand participated in an occupational
      therapy workshop group. Pre- and post-workshop grip strength and activities of
      daily living, with and without adaptive equipment were measured. 

PMID- 24440890
TI  - Tiagabine-induced stupor - more evidence for an encephalopathy.

PMID- 24440891
TI  - Treatment with melatonin after status epilepticus attenuates seizure activity and
      neuronal damage but does not prevent the disturbance in diurnal rhythms and
      behavioral alterations in spontaneously hypertensive rats in kainate model of
      temporal lobe epilepsy.
AB  - Melatonin is involved in the control of circadian and seasonal rhythmicity,
      possesses potent antioxidant activity, and exerts a neuroprotective and
      anticonvulsant effect. Spontaneously hypertensive rats (SHRs) are widely accepted
      as an experimental model of essential hypertension with hyperactivity, deficient
      sustained attention, and alterations in circadian autonomic profiles. The purpose
      of the present study was to determine whether melatonin treatment during
      epileptogenesis can prevent the deleterious consequences of status epilepticus
      (SE) in SHRs in the kainate (KA) model of temporal lobe of epilepsy (TLE).
      Spontaneous recurrent seizures (SRSs) were EEG- and video-recorded during and
      after the treatment protocol. Melatonin (10mg/kg diluted in drinking water,
      8weeks) increased the seizure-latent period, decreased the frequency of SRSs, and
      attenuated the circadian rhythm of seizure activity in SHRs. However, melatonin
      was unable to affect the disturbed diurnal rhythms and behavioral changes
      associated with epilepsy, including the decreased anxiety level, depression, and
      impaired spatial memory. Melatonin reduced neuronal damage specifically in the
      CA1 area of the hippocampus and piriform cortex and decreased hippocampal
      serotonin (5-HT) levels both in control and epileptic SHRs. Although long-term
      melatonin treatment after SE shows a potential to attenuate seizure activity and
      neuronal loss, it is unable to restore epilepsy-associated behavioral
      abnormalities in SHRs. 

PMID- 24440892
TI  - Shape-controlled synthesis of palladium and copper superlattice nanowires for
      high-stability hydrogen sensors.
AB  - For hydrogen sensors built with pure Pd nanowires, the instabilities causing
      baseline drifting and temperature-driven sensing behavior are limiting factors
      when working within a wide temperature range. To enhance the material stability,
      we have developed superlattice-structured palladium and copper nanowires (PdCu
      NWs) with random-gapped, screw-threaded, and spiral shapes achieved by wet
      chemical approaches. The microstructure of the PdCu NWs reveals novel
      superlattices composed of lattice groups structured by four-atomic layers of
      alternating Pd and Cu. Sensors built with these modified NWs show significantly
      reduced baseline drifting and lower critical temperature (259.4 K and 261 K
      depending on the PdCu structure) for the reverse sensing behavior than those with
      pure Pd NWs (287 K). Moreover, the response and recovery times of the PdCu NWs
      sensor were of ~9 and ~7 times faster than for Pd NWs sensors, respectively. 

PMID- 24440893
TI  - Are 2 weeks of "take-home" privileges beneficial for patients' long-term outcome
      in a methadone maintenance treatment program?
AB  - OBJECTIVE: Patients in Israeli methadone maintenance treatment can achieve a
      maximum of 2 weeks of take-home dose (13-THD) privileges after at least 2 years
      since the achievement of 1-week privileges (6-THD). Patients who ever achieved 6
      THD were characterized to predict achievement of 13-THD. METHODS: All patients
      who ever achieved 6-THD and then achieved 13-THD were studied (December 2010
      December 2012). Information on drugs in urine on admission, demographics, and
      addiction characteristics was retrieved from medical charts. Retention in
      treatment and duration with THD were calculated and analyzed by Kaplan-Meier and
      Cox model regression. RESULTS: Fifty-five of the 161 patients who achieved 6-THD
      also achieved 13-THD. No benzodiazepine abuse on admission (odds ratio [OR] =
      2.3, 95% confidence interval [CI]: 1.1-4.7), being Israeli-born (OR = 2.3, 95%
      CI: 1.1-5.2), and less than 12 years of education (OR = 2.8, 95% CI: 1.1-7.1)
      predicted the 13-THD achievers. The time to achieve 6-THD was shorter for the 13
      THD patients than for the 106 who achieved only 6-THD (1.7 +/- 1.5 vs. 2.3 +/-
      2.0 years, P = 0.07). After losing THD privileges, the 13-THD group showed a
      worse outcome than the 6-THD group: 1 year after losing 6-THD (n = 92) or 13-THD
      (n = 27), 3.3% of the former left treatment versus 14.8% of the latter, whereas
      83.7% versus 70.4%, respectively, succeeded in regaining any THD and 12.0% versus
      14.8%, respectively, failed altogether. CONCLUSIONS: Patients who achieved 13-THD
      were characterized by more rapid progress in rehabilitation, but those who failed
      and lost 13-THD privileges were at a higher risk to deteriorate further than
      those who failed after achieving 6-THD.

PMID- 24440894
TI  - Multiple and substitute addictions involving prescription drugs misuse among 12th
      graders: gateway theory revisited with Market Basket Analysis.
AB  - OBJECTIVES: This study aimed to identify the sequential patterns of drug use
      initiation, which included prescription drugs misuse (PDM), among 12th-grade
      students in Indiana. The study also tested the suitability of the data mining
      method Market Basket Analysis (MBA) to detect common drug use initiation
      sequences in large-scale surveys. METHODS: Data from 2007 to 2009 Annual Surveys
      of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were
      used for this study. A close-ended, self-administered questionnaire was used to
      ask adolescents about the use of 21 substance categories and the age of first
      use. "Support%" and "confidence%" statistics of Market Basket Analysis detected
      multiple and substitute addictions, respectively. RESULTS: The lifetime
      prevalence of using any addictive substance was 73.3%, and it has been decreasing
      during past few years. Although the lifetime prevalence of PDM was 19.2%, it has
      been increasing. Males and whites were more likely to use drugs and engage in
      multiple addictions. Market Basket Analysis identified common drug use initiation
      sequences that involved 11 drugs. High levels of support existed for associations
      among alcohol, cigarettes, and marijuana, whereas associations that included
      prescription drugs had medium levels of support. CONCLUSIONS: Market Basket
      Analysis is useful for the detection of common substance use initiation sequences
      in large-scale surveys. Before initiation of prescription drugs, physicians
      should consider the adolescents' risk of addiction. Prevention programs should
      address multiple addictions, substitute addictions, common sequences in drug use
      initiation, sex and racial differences in PDM, and normative beliefs of parents
      and adolescents in relation to PDM.

PMID- 24440895
TI  - Generation of a spin-polarized electron beam by multipole magnetic fields.
AB  - The propagation of an electron beam in the presence of transverse magnetic fields
      possessing integer topological charges is presented. The spin-magnetic
      interaction introduces a nonuniform spin precession of the electrons that gains a
      space-variant geometrical phase in the transverse plane proportional to the
      field's topological charge, whose handedness depends on the input electron's spin
      state. A combination of our proposed device with an electron orbital angular
      momentum sorter can be utilized as a spin-filter of electron beams in a mid
      energy range. We examine these two different configurations of a partial spin
      filter generator numerically. The results of this analysis could prove useful in
      the design of an improved electron microscope. 

PMID- 24440896
TI  - Removal processes of disinfection byproducts in subsurface-flow constructed
      wetlands treating secondary effluent.
AB  - The removal efficiencies and the kinetics of disinfection byproducts (DBPs) were
      studied in six greenhouse laboratory-scale SSF CWs. Cattail (Typha latifolia) and
      its litter (collected from the aboveground samples of cattail in autumn) were
      used as a potential phytoremediation technology and as a primary substrate,
      respectively, for DBP removal. Results showed that most of the 11 DBPs (except
      chloroform and 1, 1-dichloropropanone) were efficiently removed (>90%) in six SSF
      CWs with hydraulic retention time of 5 d and there were no significant
      differences among the systems. Under the batch mode, the removal of DBPs in SSF
      CWs followed first-order kinetics with half-lives of 1.0-770.2 h. As a primary
      DBP in wastewater effluent, removal efficiencies for chloroform were higher in
      planted systems than in unplanted ones and plant uptake accounted for more than
      23.8% of the removal. Plant litter greatly enhanced the removal of
      trihalomethanes (THMs) by supplying primary substrates and reducing conditions,
      and the formation of dichloromethane supported the anaerobic biodegradation of
      THMs via reductive dechlorination in SSF CWs. Trichloroacetonitrile was
      completely removed within 10 h in each system and hydrolysis was considered to be
      the dominant process as there was a rapid formation of the hydrolysis byproduct,
      trichloroacetamide. 

PMID- 24440897
TI  - Microtubules and spermatogenesis.
AB  - Microtubules are dynamic polymers of tubulin subunits that underpin many
      essential cellular processes, such as cell division and migration.
      Spermatogenesis is the process by which spermatogenic stem cells undergo mitotic
      and meiotic division and differentiation to produce streamlined spermatozoa
      capable of motility and fertilization. This review summarizes the current
      knowledge of microtubule-based processes in spermatogenesis. We describe the
      involvement of microtubule dynamics in Sertoli cell shape and function, as well
      as in the mitotic and meiotic division of germ cells. The roles of microtubules
      in sperm head shaping, via the development and function of the manchette, and in
      sperm flagella development are also discussed. The review brings together data
      from microscopy studies and genetically modified mouse models, and reveals that
      the regulation of microtubule dynamics is essential for male fertility. 

PMID- 24440905
TI  - Radiotherapy planning for glioblastoma based on a tumor growth model:
      implications for spatial dose redistribution.
AB  - Gliomas differ from many other tumors as they grow infiltratively into the brain
      parenchyma rather than forming a solid tumor mass with a well-defined boundary.
      Tumor cells can be found several centimeters away from the central tumor mass
      that is visible using current imaging techniques. The infiltrative growth
      characteristics of gliomas question the concept of a radiotherapy target volume
      that is irradiated to a homogeneous dose-the standard in current clinical
      practice. We discuss the use of the Fisher-Kolmogorov glioma growth model in
      radiotherapy treatment planning. The phenomenological tumor growth model assumes
      that tumor cells proliferate locally and migrate into neighboring brain tissue,
      which is mathematically described via a partial differential equation for the
      spatio-temporal evolution of the tumor cell density. In this model, the tumor
      cell density drops approximately exponentially with distance from the visible
      gross tumor volume, which is quantified by the infiltration length, a parameter
      describing the distance at which the tumor cell density drops by a factor of e.
      This paper discusses the implications for the prescribed dose distribution in the
      periphery of the tumor. In the context of the exponential cell kill model, an
      exponential fall-off of the cell density suggests a linear fall-off of the
      prescription dose with distance. We introduce the dose fall-off rate, which
      quantifies the steepness of the prescription dose fall-off in units of Gy mm(-1).
      It is shown that the dose fall-off rate is given by the inverse of the product of
      radiosensitivity and infiltration length. For an infiltration length of 3 mm and
      a surviving fraction of 50% at 2 Gy, this suggests a dose fall-off of
      approximately 1 Gy mm(-1). The concept is illustrated for two glioblastoma
      patients by optimizing intensity-modulated radiotherapy plans. The dose fall-off
      rate concept reflects the idea that infiltrating gliomas lack a defined boundary
      and are characterized by a continuous fall-off of the density of infiltrating
      tumor cells. The approach can potentially be used to individualize the prescribed
      dose distribution if better methods to estimate radiosensitivity and infiltration
      length on a patient by patient basis become available. 

PMID- 24440906
TI  - Antiplasmodial and cytotoxic dibenzofurans from Preussia sp. harboured in Enantia
      chlorantha Oliv.
AB  - Two unusual dibenzofurans, preussiafurans A-B (1-2), together with six known
      compounds have been isolated from the fungus Preussia sp. occurring in Enantia
      chlorantha Oliv. The structures were established on the basis of 1D and 2D NMR
      spectroscopy and MS analysis. Compounds 1-4 showed antiplasmodial activity
      against erythrocytic stages of chloroquine-resistant Plasmodium falciparum (NF54)
      and moderate cytotoxicity on L6 cell lines with IC50 values of 8.67 and 14.8 MUM,
      respectively.

PMID- 24440907
TI  - Hormone-sensitive lipase is involved in the action of hydroxysafflor yellow A
      (HYSA) inhibiting adipogenesis of 3T3-L1cells.
AB  - BACKGROUND: Safflor yellow A (SY) has been demonstrated to be beneficial to
      cardiovascular system. Our previous study showed that hydroxysafflor yellow A
      (HSYA), a main component of SY, could increase peroxisome proliferator-activated
      receptor gamma mRNA expression. In this study, we investigate the effect of HSYA
      on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. METHODS: The
      proliferation and adipogenesis of 3T3-L1 cells treated with HSYA was studied by 3
      (4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT)
      spectrophotometry, Oil Red O staining and intracellular triglyceride assay
      methods. HSL mRNA expression and promoter activity were studied by real-time
      quantitative RT-PCR, transient transfection and dual luciferase reporter gene
      methods. RESULTS: HSYA (0.1 mg/L) significantly inhibited the proliferation of
      3T3-L1 cells when compared with control cells in 8 h. This effect was further
      enhanced with the extension time (24 to 96 h) and an increase of concentration of
      HSYA (1-10 mg/L). The maximal inhibitory action was observed at 0.1 mg/L HSYA in
      72 h (86+/-11.8% vs. 100+/-4.1%, p<0.01). HSYA notably reduced the amount of
      intracellular lipid and triglyceride content in adipocytes to 85% (1 mg/L) and
      75% (100 mg/L) on Day 4 following the differentiation, respectively, while
      increased HSL mRNA expression and promoter activities to 2.7 fold and 1.55 fold,
      respectively (p<0.01), in differentiated 3T3-L1 adipocytes. CONCLUSIONS: HSYA
      inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The
      inhibitory action of HYSA on adipogenesis may be due to the promotion of
      lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.

PMID- 24440908
TI  - Viral pathogens in water: occurrence, public health impact, and available control
      strategies.
AB  - The public health impact of the transmission of viruses in water is significant
      worldwide. Waterborne viruses can be introduced into our recreational and
      finished drinking water sources through a variety of pathways ultimately
      resulting in the onset of illness in a portion of the exposed population.
      Although there have been advances in both drinking water treatment technologies
      and source water protection strategies, waterborne disease outbreaks (WBDOs) due
      to viral pathogens still occur each year worldwide. By highlighting the
      prevalence of viral pathogens in water as well as (1) the dominant viruses of
      concern, (2) WBDOs due to viruses, and (3) available water treatment
      technologies, the goal of this review is to provide insight into the public
      health impact of viruses in water. 

PMID- 24440909
TI  - A novel role for the apoptosis inhibitor ARC in suppressing TNFalpha-induced
      regulated necrosis.
AB  - TNFalpha signaling can promote apoptosis or a regulated form of necrosis. ARC
      (apoptosis repressor with CARD (caspase recruitment domain)) is an endogenous
      inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and
      intrinsic (mitochondrial/ER) apoptosis pathways. We discovered that ARC blocks
      not only apoptosis but also necrosis. TNFalpha-induced necrosis was abrogated by
      overexpression of wild-type ARC but not by a CARD mutant that is also defective
      for inhibition of apoptosis. Conversely, knockdown of ARC exacerbated TNFalpha
      induced necrosis, an effect that was rescued by reconstitution with wild-type,
      but not CARD-defective, ARC. Similarly, depletion of ARC in vivo exacerbated
      necrosis caused by infection with vaccinia virus, which elicits severe tissue
      damage through this pathway, and sensitized mice to TNFalpha-induced systemic
      inflammatory response syndrome. The mechanism underlying these effects is an
      interaction of ARC with TNF receptor 1 that interferes with recruitment of RIP1,
      a critical mediator of TNFalpha-induced regulated necrosis. These findings extend
      the role of ARC from an apoptosis inhibitor to a regulator of the TNFalpha
      pathway and an inhibitor of TNFalpha-mediated regulated necrosis. 

PMID- 24440910
TI  - p63 is a prosurvival factor in the adult mammary gland during post-lactational
      involution, affecting PI-MECs and ErbB2 tumorigenesis.
AB  - In embryogenesis, p63 is essential to develop mammary glands. In the adult
      mammary gland, p63 is highly expressed in the basal cell layer that comprises
      myoepithelial and interspersed stem/progenitor cells, and has limited expression
      in luminal epithelial cells. In adult skin, p63 has a crucial role in the
      maintenance of epithelial stem cells. However, it is unclear whether p63 also has
      an equivalent role as a stem/progenitor cell factor in adult mammary epithelium.
      We show that p63 is essential in vivo for the survival and maintenance of parity
      identified mammary epithelial cells (PI-MECs), a pregnancy-induced heterogeneous
      population that survives post-lactational involution and contain multipotent
      progenitors that give rise to alveoli and ducts in subsequent pregnancies. p63+/-
      glands are normal in virgin, pregnant and lactating states. Importantly, however,
      during the apoptotic phase of post-lactational involution p63+/- glands show a
      threefold increase in epithelial cell death, concomitant with increased
      activation of the oncostatin M/Stat3 and p53 pro-apoptotic pathways, which are
      responsible for this phase. Thus, p63 is a physiologic antagonist of these
      pathways specifically in this regressive stage. After the restructuring phase
      when involution is complete, mammary glands of p63+/- mice again exhibit normal
      epithelial architecture by conventional histology. However, using Rosa(LSL
      LacZ);WAP-Cre transgenics (LSL-LacZ, lox-stop-lox beta-galactosidase), a genetic
      in vivo labeling system for PI-MECs, we find that p63+/- glands have a 30%
      reduction in the number of PI-MEC progenitors and their derivatives. Importantly,
      PI-MECs are also cellular targets of pregnancy-promoted ErbB2 tumorigenesis.
      Consistent with their PI-MEC pool reduction, one-time pregnant p63+/- ErbB2 mice
      are partially protected from breast tumorigenesis, exhibiting extended tumor-free
      and overall survival, and reduced tumor multiplicity compared with their p63+/+
      ErbB2 littermates. Conversely, in virgin ErbB2 mice p63 heterozygosity provides
      no survival advantage. In sum, our data establish that p63 is an important
      survival factor for pregnancy-identified PI-MEC progenitors in breast tissue in
      vivo. 

PMID- 24440911
TI  - Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS,
      STAT5B, and glioblastoma.
AB  - Receptor tyrosine kinases (RTKs) are co-deregulated in a majority of glioblastoma
      (GBM), the most common and most deadly brain tumor. We show that the RTKs MET,
      EGFR, and PDGFR regulate microRNA-134 (miR-134) in GBM. We find that miR-134 is
      downregulated in human tumors and cancer stem cells and that its expression
      inversely correlates with the activation of MET, EGFR, and PDGFR. We demonstrate
      that miR-134 inhibits cancer cell and stem-cell proliferation, survival, and
      xenograft growth, as well as cancer stem-cell self-renewal and stemness. We
      identify KRAS and STAT5B as targets of miR-134, and establish molecular and
      functional links between RTKs, miR-134, KRAS/STAT5B and malignancy in vitro and
      in vivo. We show that miR-134 induction is required for the anti-tumor effects of
      RTK inhibitors. We also uncover the molecular pathways through which RTKs
      regulate miR-134 expression and demonstrate the involvement of MAPK signaling and
      the KLF4 transcription factor. We therefore identify miR-134 as a novel RTK
      regulated tumor-suppressive hub that mediates RTK and RTK-inhibitor effects on
      GBM malignancy by controlling KRAS and STAT5B. 

PMID- 24440913
TI  - The 6th International p63/p73 Workshop: the C(ancer) and D(evelopmental) roles of
      p63 and p73.

PMID- 24440912
TI  - ADAR1 deaminase contributes to scheduled skeletal myogenesis progression via
      stage-specific functions.
AB  - Adenosine deaminases acting on RNA 1 (ADAR1) catalyzes cellular RNA adenosine-to
      inosine editing events on structured RNA molecules. In line with this critical
      role, ADAR1 exhibits ubiquitous expression and is essential for embryonic
      development. However, regulation and developmental significance of this RNA
      editor in a spatiotemporal context are largely elusive. Here we unveil a novel
      tissue-specific role of ADAR1 in skeletal myogenesis. ADAR1 expression displayed
      programmed alteration that is coordinated with differentiation cues, and mediated
      negatively by miRNA-1/206. Coincidently, ADAR1 exerts stage-dependent functions
      suppression of apoptosis at the onset of differentiation and preservation of
      timely myotube formation through later phase. Furthermore, the post
      transcriptional aspect of its myogenic role was illustrated by the spectrum of
      binding RNAs, as revealed by high-throughput approach, as well as by direct
      regulation of myogenesis-associated targets such as dynamin 1/2 (Dnm1/2) and
      annexin A4. Consequently, maintenance of target gene expression profiles likely
      contributes to a state of cytoskeleton and membrane dynamics that is amenable to
      myoblast morphogenesis. Collectively, these findings uncover a critical link of
      ADAR1 to myogenesis, and further highlight an epigenetic mechanism by which ADAR1
      and miR-1/206 interplay to control scheduled myoblast-myotube transition. 

PMID- 24440915
TI  - Eucommia ulmoides Oliv. bark. attenuates 6-hydroxydopamine-induced neuronal cell
      death through inhibition of oxidative stress in SH-SY5Y cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. Bark. (EUE) has commonly
      been used to fortify the muscles and lungs, lower blood pressure, prevent
      miscarriage, improve liver and kidney tone, and promote longevity as a
      traditional tonic medicine in Korea, China, and Japan. AIM OF THE STUDY: In this
      study, we investigated the mechanisms by which EUE protects neuronal cells from
      apoptosis induced by the Parkinson's disease (PD)-related neurotoxin, 6
      hydroxydopamine (6-OHDA). MATERIALS AND METHODS: We determined the
      neuroprotective effects of EUE on 6-OHDA-induced neuronal cell death,
      cytotoxicity, reactive oxygen species (ROS) production, and mitochondrial
      membrane dysfunction. Moreover, we examined whether EUE suppressed
      phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase
      (PI3K)/Akt, and glycogen synthase kinase-3 beta (GSK-3beta). Furthermore, the
      neuroprotective effects of EUE on 6-OHDA-induced activation of nuclear factor
      kappa B (NF-kappaB) was studied in SH-SY5Y cells. RESULTS: Pretreatment of SH
      SY5Y cells with EUE significantly reduced 6-OHDA-induced cell death and
      cytotoxicity. EUE inhibited 6-OHDA-induced generation of ROS, which conferred
      cytoprotection against 6-OHDA-induced oxidative injury. EUE treatment also
      strikingly inhibited 6-OHDA-induced mitochondrial dysfunction. In addition, EUE
      suppressed phosphorylation of JNK, PI3K/Akt, and GSK-3beta. Furthermore, EUE
      blocked 6-OHDA-induced NF-kappaB nuclear translocation, an event downstream from
      JNK, PI3K/Akt, and GSK-3beta phosphorylation. Moreover, chlorogenic acid (CGA),
      one of the active constituents of EUE, was also able to reduce 6-OHDA-induced
      toxicity in SH-SY5Y cells. CONCLUSION: Taken together, these results suggest that
      EUE attenuates oxidative stress through activation of JNK, PI3K/Akt, GSK-3beta,
      and NF-kappaB pathways, thereby protecting cells from neuronal cell death.

PMID- 24440916
TI  - Investigation of a link between raised levels of pepsinogen in blood as a
      mediator of in-vitro clot lysis in acid and a cause of abnormal factor XIII
      screening tests.
AB  - The in-vitro lysis of plasma clots in acetic acid generally indicates a Factor
      XIII deficiency that is confirmed by quantitative assay. However, there are two
      rare, poorly understood circumstances whereby clot lysis in acid occurs when
      factor XIII activity levels are normal: the presence of either an atypical
      antifactor XIII antibody, or an unknown acid-activated protease. Our centre has
      identified four patients with in-vitro clot lysis in acetic acid and normal FXIII
      levels by activity assay. Our aim was to determine whether the cause of this
      unusual result was an inhibitory antibody or an aspartic acid protease. In each
      case, we found an inhibitor that was not an IgG but showed characteristics of an
      acid protease, including that it was neutralized by pepstatin. The four patients
      had median pepsinogen I levels five-fold to 10-fold higher than the normal median
      of 89 MUg/l. Pepsinogen II was increased by three-fold to six-fold, but from a
      lower baseline median of 6.5 MUg/l. Cathepsin D levels were normal. Clot lysis in
      the acid test was observed when recombinant human pepsinogen I was added to
      normal plasma at similarly high concentrations as in patient samples, consistent
      with a role of an acid protease. Clot lysis also occurred with addition of
      pepsinogen II, but required four-fold to seven-fold more than in patient samples.
      Laboratories should be aware that a positive acid clot lysis test can be
      misleading if pepsinogen levels are raised and should not use this alone to
      diagnose FXIII deficiency.

PMID- 24440914
TI  - Regulation of autophagy by the Rab GTPase network.
AB  - Autophagy (macroautophagy) is a highly conserved intracellular and lysosome
      dependent degradation process in which autophagic substrates are enclosed and
      degraded by a double-membrane vesicular structure in a continuous and dynamic
      vesicle transport process. The Rab protein is a small GTPase that belongs to the
      Ras-like GTPase superfamily and regulates the vesicle traffic process. Numerous
      Rab proteins have been shown to be involved in various stages of autophagy. Rab1,
      Rab5, Rab7, Rab9A, Rab11, Rab23, Rab32, and Rab33B participate in autophagosome
      formation, whereas Rab9 is required in non-canonical autophagy. Rab7, Rab8B, and
      Rab24 have a key role in autophagosome maturation. Rab8A and Rab25 are also
      involved in autophagy, but their role is unknown. Here, we summarize new findings
      regarding the involvement of Rabs in autophagy and provide insights regarding
      future research on the mechanisms of autophagy regulation. 

PMID- 24440917
TI  - From genome to phenome and back in tomato.
AB  - The tomato is an ideal plant species for genomic and evolutionary studies. Thanks
      to recent technical advances, a plethora of information relating to tomato
      genomics has been generated. In addition, various phenotypes related to
      morphology, physiology and yield have been investigated in tomato and its wild
      relatives. In this review, we summarize recent key findings in tomato genomics
      that used both developmental and evolutionary approaches to link the genome to
      phenome. Combined, these perspectives allow us to look at the trends in tomato
      evolution in addition to providing insight into the future direction of research
      that can utilize this unique model species. 

PMID- 24440919
TI  - Implementation cost analysis of a community-based exercise program for seniors in
      South Florida.
AB  - The objective of the study was to measure the costs of implementing the
      EnhanceFitness program to elderly residents of South Florida. The Health
      Foundation of South Florida's Healthy Aging Regional Collaborative implemented
      EnhanceFitness as part of their initiative to make evidence-based healthy aging
      programs available to South Florida seniors. Cost data were collected from
      agencies participating in the delivery of EnhanceFitness classes in South
      Florida. Cost questionnaires were e-mailed to program coordinators from agencies
      participating in the delivery of EnhanceFitness classes. Program coordinators
      worked with accounting staff to complete the questionnaires. Questionnaires were
      returned via e-mail. Costs were presented from the perspective of participating
      agencies. Total costs were divided by the number of classes being offered by each
      agency to determine cost per class per month. Average monthly costs per class
      were $1,713 during the first year of implementation and $873 during the second
      year of implementation. The cost measurements, combined with information from the
      literature on cost savings attributable to EnhanceFitness participation, suggest
      that EnhanceFitness has the potential to generate a net societal cost savings
      among program participants. The results are useful for community agencies
      considering implementing EnhanceFitness for their populations. 

PMID- 24440921
TI  - Can the inpatient hospital setting be a golden opportunity to improve colon
      cancer screening rates in the United States?
AB  - BACKGROUND: Colorectal cancer is the third most common cancer in the United
      States. Despite efforts to increase colorectal cancer screening, the rate of
      compliance with the recommended screening remains relatively suboptimal according
      the American Cancer Society (53%). PURPOSE: To assess whether the time of
      hospitalization is a suitable opportunity for patients to receive counseling and
      for recruiting patients to undergo screening colonoscopy for colon cancer.
      METHOD: In 2009, we conducted a cross-sectional survey of hospitalized adults age
      50 to 80 years in order to assess their responses on a modified version of the
      Health Information National Trends Survey. We conducted chi(2) analyses on these
      data to examine the differences in patients' knowledge of colorectal cancer
      screening and prior adherence to screening guidelines and to assess whether they
      would be willing to undergo a screening in the near future if prompted by their
      physicians. RESULTS: We enrolled a total of 332 participants to complete the
      study questionnaire. About 94% of the subjects had heard about colon cancer, and
      83.4% had heard of any screening tests to detect colorectal cancer. About 66% of
      subjects reported the colonoscopy to be the most effective screening test for
      colon cancer. Approximately 55% of the total sample group adhered to recommended
      screening guidelines for colon cancer using the colonoscopy. CONCLUSIONS: The
      time of hospitalization is a potential "golden opportunity" to counsel patients
      and promote colon cancer screening.

PMID- 24440920
TI  - Development, theoretical framework, and evaluation of a parent and teacher
      delivered intervention on adolescent vaccination.
AB  - The Advisory Committee on Immunization Practices recommended immunization
      schedule for adolescents includes three vaccines (tetanus, diphtheria, and
      acellular pertussis [Tdap]; human papillomavirus [HPV] vaccine; and meningococcal
      conjugate vaccine [MCV4]) and an annual influenza vaccination. Given the
      increasing number of recommended vaccines for adolescents and health and economic
      costs associated with nonvaccination, it is imperative that effective strategies
      for increasing vaccination rates among adolescents are developed. This article
      describes the development, theoretical framework, and initial first-year
      evaluation of an intervention designed to promote vaccine acceptance among a
      middle and high school-based sample of adolescents and their parents in eastern
      Georgia. Adolescents, parents, and teachers were active participants in the
      development of the intervention. The intervention, which consisted of a brochure
      for parents and a teacher-delivered curriculum for adolescents, was guided by
      constructs from the health belief model and theory of reasoned action. Evaluation
      results indicated that our intervention development methods were successful in
      creating a brochure that met cultural relevance and the literacy needs of
      parents. We also demonstrated an increase in student knowledge of and positive
      attitudes toward vaccines. To our knowledge, this study is the first to
      extensively engage middle and high school students, parents, and teachers in the
      design and implementation of key theory-based educational components of a school
      based, teacher-delivered adolescent vaccination intervention. 

PMID- 24440922
TI  - Patterns of traffic polycyclic aromatic hydrocarbon pollution in mountain areas
      can be revealed by lichen biomonitoring: a case study in the Dolomites (Eastern
      Italian Alps).
AB  - In mountain areas of touristic interest the evaluation of the impact of human
      activities is crucial for ensuring long-term conservation of ecosystem
      biodiversity, functions and services. This study aimed at verifying the
      biological impact of polycyclic aromatic hydrocarbon (PAH) emissions due to
      traffic along the roads leading to seven passes of the Dolomites (SE Alps), which
      were recently declared a UNESCO World Heritage Site. Thalli of the epiphytic
      lichen Pseudevernia furfuracea, collected at increasing distances from the roads,
      were used as biomonitors. Our study revealed a gradient of decreasing PAH
      pollution within 300 m from the roads. Differences among passes were evident
      mainly for samples collected nearest to the roads, but PAH concentrations at 300
      m were almost always higher than those of undisturbed reference sites, indicating
      that traffic PAH pollution may impact natural ecosystems and lichen diversity at
      relatively long distances from the emission source.

PMID- 24440923
TI  - A copper(I)/copper(II)-salen coordination polymer as a bimetallic catalyst for
      three-component Strecker reactions and degradation of organic dyes.
AB  - A copper(i)/copper(ii)-salen coordination polymer prepared by solvothermal
      reactions shows prominent bimetallic catalytic activities towards three-component
      Strecker reactions and photodegradation of organic dyes under visible-light
      illumination. 

PMID- 24440924
TI  - Early presentation of bowel perforation due to fish bone ingestion.

PMID- 24440925
TI  - A novel regulator of lung inflammation and immunity: pulmonary parasympathetic
      inflammatory reflex.
AB  - In this review, we first analyzed the current status of cholinergic anti
      inflammatory pathway and then put forward a novel regulatory machinery-pulmonary
      parasympathetic inflammatory reflex, which is composed by lung vagal sensors at
      afferent arm, alpha7 nAChR (alpha7 nicotinic acetylcholine receptors)-expressing
      cells at efferent arm and the brain information integrating center. This
      modulatory circuit might loop the lungs, immune and nervous systems and play a
      very important role in regulating lung infection, inflammation and immunity
      through the neural innervations and signals when the lungs encounter pathogenic
      challenges. 

PMID- 24440926
TI  - Hepatopulmonary syndrome : a rare diagnosis or easily missed entity?

PMID- 24440927
TI  - Russell W Brain and the aetiology of multiple sclerosis--a historical
      perspective.
AB  - The contribution of British neurologist Russell Walter Brain (1895-1966) to the
      field of neurology is difficult to overestimate and his seminal work continues to
      influence modern neurological education and practice. In a landmark review
      published in the Quarterly Review of Medicine in 1930, he gives a critically
      important account summarising ideas of the time thought to underlie the then
      called 'disseminated sclerosis', a disease he notes to be, 'after syphilis, the
      most frequent disease of the nervous system' in the UK. Across a century and a
      half, vast progress has been made in attempting to elucidate the as yet unknown
      cause of MS, which is unravelling to be multifactorial, highly complex and likely
      dependent on both genetic and environmental risk factors. Brain's observations
      highlight the changing epidemiology of MS over the last century which are likely
      to provide the platform in striving towards elucidating MS causation, notably a
      seemingly reduced latitudinal gradient of MS incidence, an increasing female-to
      male sex ratio and an increasing disease rate in dark-skinned compared to light
      skinned individuals. In this report we aim to evaluate the relevance today of
      what we believe to have been an important review demonstrating a perspective on
      MS far ahead that of its time, with a focus on Brain's ideas on the aetiology of
      MS; many of which have stood the test of time.

PMID- 24440928
TI  - Giant pulmonary bullae mimicking spontaneous pneumothorax.

PMID- 24440929
TI  - Calprotectin in bile: a disease severity marker in patients with primary
      sclerosing cholangitis.
AB  - GOALS: Our aim was to evaluate the diagnostic potential of calprotectin in serum
      and bile of patients with primary sclerosing cholangitis (PSC). BACKGROUND: PSC
      is a chronic cholestatic liver disease of unknown etiology. It is characterized
      by progressive inflammation and fibrosis of the bile ducts leading to biliary
      cirrhosis and eventually liver failure. Reliable markers for disease activity and
      severity are still lacking. Subunits of calprotectin, a fecal marker of
      inflammation in inflammatory bowel disease, have been recently identified in
      bile. STUDY: Calprotectin was measured in patients with PSC (n=56),
      cholangiocarcinoma (CC) complicating PSC (CC/PSC) (n=13), CC (n=30), and bile
      duct stones in bile (n=38) and serum (n=73) by enzyme-linked immunosorbent assay
      in a cross-sectional study. PSC patients were categorized by the Mayo risk score
      (MRS) to characterize the disease severity. RESULTS: Calprotectin is present in
      bile, and the median concentration was significantly higher in PSC patients
      (P<0.05). Stratification of PSC patients by MRS showed significantly elevated
      calprotectin levels in bile in the MRS-high group (P<0.05). Calprotectin and MRS
      correlated significantly (P<0.05). The presence or absence of inflammatory bowel
      disease in PSC patients did not alter calprotectin levels in bile. Serum AP and
      calprotectin in bile correlated significantly (P=0.013). No significant
      correlation was found for other liver-related parameters. In contrast, serum
      calprotectin levels were significantly higher in patients with CC, but there was
      no association with PSC or disease activity/severity. CONCLUSIONS: Calprotectin
      in bile is a promising disease marker in patients with PSC with a potential
      prognostic value.

PMID- 24440930
TI  - Esophageal pressure topography, body position, and hiatal hernia.
AB  - INTRODUCTION: Whether body position affects lower esophageal sphincter (LES)
      function and detection of hiatal hernia is unknown. Moreover, the yield of high
      resolution esophageal pressure topography (HREPT) when compared with endoscopy
      for detection of hiatal hernia is unclear. AIM: The aims of this study were to
      examine (a) the effects of body position (standing vs. supine) on LES function,
      and (b) to determine the diagnostic yield of HREPT and endoscopy for detection of
      hiatal hernia. METHODS: A total of 50 subjects underwent both HREPT and
      endoscopy. The manometric/topographic changes of LES were examined in both supine
      and standing positions. Endoscopy assessed presence and length of hiatal hernia.
      Diagnostic agreement was compared between HREPT and endoscopy. RESULTS: The
      resting LES pressure was higher (P=0.0001), its mean length was longer
      (P=0.0003), and length of high-pressure zone was longer (P=0.0001) in the
      standing position compared with the supine position. HREPT detected twice as many
      subjects with hiatal hernia in standing (P=0.0001) compared with supine position
      or endoscopy with significant new diagnostic information (79%). Endoscopy
      detection rate (34%) was similar to supine manometry with good diagnostic
      agreement (77%) between HREPT and endoscopy. Hiatal hernia length was longer
      (P=0.0001) with HREPT in standing position compared with endoscopy. CONCLUSIONS:
      Body position significantly affects in the LES function and its measurements.
      HREPT when performed on standing position offers the best yield for detection of
      hiatal hernia and is superior to endoscopy or supine manometry.

PMID- 24440931
TI  - Efficacy and safety of cinitapride in the treatment of mild to moderate
      postprandial distress syndrome-predominant functional dyspepsia.
AB  - GOALS AND BACKGROUND: Functional dyspepsia (FD) is a complex disease with a
      variety of dyspeptic symptoms. Little is known about the clinical efficacy of
      cinitapride, a 5-HT4 agonist and D2 antagonist, in treating FD. STUDY: This
      randomized, double-blind, double-dummy, positive-controlled study compared the
      efficacy and safety of cinitapride (1 mg) and domperidone (10 mg) tid for 4 weeks
      in 383 consecutive patients with mild to moderate, postprandial distress syndrome
      predominant dyspeptic symptoms according to Rome III criteria. The primary
      endpoint was the noninferiority of cinitapride compared with domperidone in
      relief of symptoms. The overall patient evaluation of treatment and open gastric
      emptying effects of both drugs were treated as the secondary endpoints. RESULTS:
      The rates of symptom relief by cinitapride and domperidone after 4 weeks did not
      differ significantly on intension-to-treat analysis (85.8% vs. 81.8%, P=0.332).
      Cinitapride significantly reduced the overall severity of postprandial fullness,
      early satiation, and bloating (4.3+/-3.9 vs. 17.8+/-6.6, P<0.001); and it was
      superior to the effects of domperidone (5.4+/-4.9 vs. 18.4+/-6.9, P<0.001;
      P=0.021 between groups). Cinitapride also decreased the mean half-gastric
      emptying time from 131.1+/-119.4 to 86.5+/-18.7 minutes (P=0.0002). There was a
      positive relationship between symptoms and gastric emptying time (r=0.332,
      P=0.041). Cinitapride-related adverse events were observed in 9.1% of patients,
      including 1 patient with extrapyramidal symptoms. No patient experienced QT
      interval prolongation. CONCLUSIONS: This phase III trial has confirmed a
      noninferior efficacy of cinitapride over domperidone for patients with mild to
      moderate, postprandial distress syndrome-predominant FD. Cinitapride usage is
      well tolerated, but its cardiovascular events need further evaluation.

PMID- 24440932
TI  - Trainee participation and adenoma detection rates during screening colonoscopies.
AB  - GOAL: To evaluate whether participation of a gastroenterology trainee had an
      impact on adenoma detection rate (ADR) during screening colonoscopies performed
      with standard-definition colonoscopes (SD-C) versus high-definition colonoscopes
      (HD-C). BACKGROUND: ADR is an established quality indicator of colonoscopy and
      efforts to improve ADR have led to technological advancements including HD-C that
      have a greater angle of view and produce an image with higher pixel density
      compared with SD-C. Moreover, other factors like trainee participation have been
      shown to improve adenoma detection. METHODS: This is a retrospective review of
      screening colonoscopies performed during 2 different time periods by 4
      experienced endoscopists with or without trainee participation. There are 2 arms
      of this study, based on whether screening colonoscopy was performed using SD-C or
      HD-C. Detailed review of endoscopy and histopathologic reports was conducted.
      Statistical analysis was performed and odds ratio and incidence rate ratios were
      calculated to adjust for numerous factors. RESULTS: No significant differences
      were seen with trainee participation in the SD-C arm of the study. In the HD-C
      arm, the total number, and the proportion of subjects with: adenomas, diminutive
      adenomas, and right-sided adenomas were significantly higher with trainee
      participation. CONCLUSIONS: Trainee participation significantly improved the
      overall adenoma detection, specifically diminutive adenoma and right-sided
      adenoma detection, but only when colonoscopies were performed with HD-C. The
      improved image quality and resolution provided by HD-C, coupled with enhanced
      visual scanning an additional pair of eyes provides, may account for the
      differential impact of trainee participation on ADR.

PMID- 24440933
TI  - Totally laparoscopic resection with natural orifice specimen extraction for
      carcinoma of sigmoid colon and rectum: a feasible and innovative technique.
AB  - GOALS: To testify the feasibility and safety of an innovative technique we
      performed. BACKGROUND: An abdominal incision is required to extract a specimen
      for laparoscopic-assisted colorectal operation, and the incision brings some
      disadvantages for surgeons and patients. Natural orifice specimen extraction
      (NOSE) is developed to avoid these disadvantages. STUDY: Between May 2012 and
      March 2013, we attempted to perform totally laparoscopic resection with NOSE in
      27 patients with sigmoid colon cancer or rectal cancer. Procedure of this
      technique was described and clinic data of all 27 patients were collected and
      analyzed. RESULTS: We successfully completed the technique of NOSE in 24 of these
      patients. Mean operation time was 110.0 minutes and mean intraoperative blood
      loss was 69.1 mL in 23 patients (not including one patient who received
      additional bilateral oophorectomy) who underwent NOSE. Of these 24 patients, the
      mean time to passing of first flatus was 3.1 days, the mean postoperative
      hospital stay was 9.2 days, and 2 patients used analgesics after operation; 22
      patients were able to walk in first 2 days, 2 patients had postoperative
      complications. CONCLUSIONS: Totally laparoscopic resection with NOSE is suited
      for selected patients with sigmoid colon cancer or rectal cancer, and this
      technique is worth to recommend and spread.

PMID- 24440934
TI  - Fecal microbiota transplantation for the treatment of Clostridium difficile
      infection: a systematic review.
AB  - GOAL: By systematic review, we assessed the impact of fecal microbiota
      transplantation (FMT) for the treatment of Clostridium difficile (CD)-associated
      diarrhea. BACKGROUND: Fecal microbiota microbiota transplantation from a healthy
      donor into an individual with CD infection (CDI) can resolve symptoms. STUDY: We
      conducted systematic searches in PubMed, SCOPUS, Web of Science, and Cochrane
      Library. The last search was run on February 8, 2013. The following Medical
      Subject Headings terms and keywords were used alone or in combination:
      Clostridium difficile; Clostridium infection; pseudomembranous colitis; feces;
      stools; fecal suspension; fecal transplantation; fecal transfer; fecal infusion;
      microbiota; bacteriotherapy; enema; nasogastric tube; colonoscopy; gastroscopy;
      fecal donation; donor. A critical appraisal of the clinical research evidence on
      the effectiveness and safety of FMT for the treatment of patients with CD
      associated diarrhea was made. RESULTS: Twenty full-text case series, 15 case
      reports, and 1 randomized controlled study were included for the final analysis.
      Almost all patients treated with donors' fecal infusion experienced recurrent
      episodes of CD-associated diarrhea despite standard antibiotic treatment. Of a
      total of 536 patients treated, 467 (87%) experienced resolution of diarrhea.
      Diarrhea resolution rates varied according to the site of infusion: 81% in the
      stomach; 86% in the duodenum/jejunum; 93% in the cecum/ascending colon; and 84%
      in the distal colon. No severe adverse events were reported with the procedure.
      CONCLUSIONS: FMT seems efficacious and safe for the treatment of recurrent CDI.
      Hospitals should encourage the development of fecal transplantation programs to
      improve therapy of local patients.

PMID- 24440935
TI  - Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in
      Crohn's disease.
AB  - GOALS: To examine the efficiency of exclusive enteral nutrition (EEN) in
      relieving inflammatory bowel stricture in patients with Crohn's disease (CD).
      BACKGROUND: Patients with CD usually develop bowel strictures due to transmural
      edema of intestinal wall, which can potentially be managed with conservative
      medical treatment. Previous studies showed that EEN therapy could induce clinical
      remission through its anti-inflammation effect. METHODS: We achieved a
      prospective observational study. CD patients with inflammatory bowel stricture
      were preliminarily differentiated from a fibrous one, and further treated with
      EEN therapy for 12 weeks. Demographics and clinical variables were recorded.
      Nutritional (body mass index, albumin, pre-albumin, transferrin, etc.),
      inflammatory (C-reactive protein, erythrocyte sedimentation rate, white blood
      cell, etc.), and radiologic parameters (bowel wall thickness, luminal diameter,
      and luminal cross-sectional area) were evaluated at baseline, week 4, and week
      12, respectively. RESULTS: Between May 2012 and January 2013, 65 patients with CD
      were preliminarily diagnosed with inflammatory bowel stricture and 6 patients
      were further excluded. Among the remaining 59 cases, 50 patients (84.7%) finished
      the whole EEN treatment, whereas the other 9 patients (15.3%) gained progressive
      bowel obstruction resulting in surgery. Intention-to-treat analyses showed that
      48 patients (81.4%) achieved symptomatic remission, 35 patients (53.8%) achieved
      radiologic remission, and 42 patients (64.6%) achieved clinical remission. Among
      those patients who complete the whole EEN therapy, inflammatory, nutritional, and
      radiologic parameters improved significantly compared with baseline. Of note, the
      average luminal cross-sectional area at the site of stricture increased
      approximately 331% at week 12 (195.7 +/- 18.79 vs. 59.09 +/- 10.64 mm, P<0.001).
      CONCLUSIONS: EEN therapy can effectively relieve inflammatory bowel stricture in
      CD, which replenishes roles of enteral nutrition in the treatment of CD. Further
      studies are expected to investigate the underlying mechanisms of this effect in
      the future.

PMID- 24440936
TI  - Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to
      insulin resistance and liver histology.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of
      metabolic syndrome. We aimed to assess the relationship of metabolic syndrome
      associated NASH and insulin resistance (IR), and to define the correlation of
      chemicometabolic components with different degree of liver histology in NASH
      subjects. STUDY: Ninety-four subjects with NASH (mean age, 38+/-14 y; 77% male)
      were enrolled. IR was calculated using a homeostasis model assessment of insulin
      resistance (HOMA-IR). Clinical characteristics including IR and accompanying
      metabolic risk components in NASH subjects were compared with those of 52
      diabetics and 21 healthy controls. The relationship between IR and
      chemicometabolic variables was analyzed according to different clustering of
      metabolic risk components and the histologic activity. RESULTS: NASH subjects had
      a stronger association with metabolic syndrome than healthy controls. HOMA-IR was
      significantly higher in NASH subjects than in healthy controls (4.4+/-2.5 vs.
      1.7+/-0.6; P<0.001) but not than in diabetics. NASH subjects with metabolic
      syndrome were more likely to have higher HOMA-IR compared with that of NASH
      subjects without metabolic syndrome (5.0+/-2.9 vs. 3.6+/-1.7; P=0.032). HOMA-IR
      showed a positive correlation with body mass index (r=0.428, P=0.015) and serum
      fasting blood sugar (r=0.365, P=0.037). Serum aspartate aminotransferase/alanine
      aminotransferase ratio (P=0.029) and high-density lipoprotein cholesterol level
      (P=0.034) were significantly affected according to the degree of fibrotic
      activity in 41 histology-proven NASH subjects. CONCLUSIONS: NASH subjects showed
      increased IR with a significant association of metabolic syndrome. The severity
      of hepatic fibrosis revealed a strong correlation with serum aspartate
      aminotransferase/alanine aminotransferase ratio and high-density lipoprotein
      cholesterol level.

PMID- 24440937
TI  - Comparison of lamivudine plus adefovir therapy versus entecavir with or without
      adefovir therapy for adefovir-resistant chronic hepatitis B.
AB  - BACKGROUND AND GOALS: Data regarding the management of adefovir (ADV) resistance
      are still limited. The aim of this study is to investigate treatment outcomes of
      rescue therapy in ADV-resistant chronic hepatitis B (CHB) patients. STUDY: CHB
      patients who began rescue therapy due to documented genotypic resistance
      mutations to ADV between October 2006 and July 2012 were retrospectively
      reviewed. RESULTS: Sixty-three patients were included in this study. Most
      patients had history of lamivudine (LAM) resistance. Treatment response was
      evaluated at 3-month intervals up to 12 months. The cumulative rate of complete
      virologic response (CVR) in hepatitis B virus (HBV)-infected patients (HBV DNA<60
      IU/mL) was 15.9%, 27.2%, 28.9%, and 31.7% after 3, 6, 9, and 12 months of rescue
      therapy. Thirty-five patients were treated with a combination of LAM plus ADV
      (LAM+ADV group) and 28 patients were treated with entecavir (ETV)-based therapy
      (ETV with or without ADV therapy, ETV+/-ADV group). The cumulative CVR rate was
      significantly higher in the ETV+/-ADV group than in the LAM+ADV group at month 12
      (46.4% vs. 20.6%, respectively, P=0.040). Multivariate analysis showed that
      pretreatment serum HBV DNA levels at <6 log10 IU/mL (hazard ratio: 34.109,
      P=0.001) and type of rescue therapy (hazard ratio: 4.944, P=0.036) were
      associated with CVR. CONCLUSIONS: Lower baseline HBV DNA level and ETV+/-ADV
      therapy were the important predictive factors for CVR in ADV-resistant CHB
      patients. This study suggests the need of early switching to a rescue therapy
      such as ETV+/-ADV at the time of low-level viremia.

PMID- 24440938
TI  - Colonization of Klebsiella pneumoniae inside fistula tracts: a possible risk
      factor for failure of fibrin glue-assisted closure.
AB  - GOALS: This study was designed to investigate the risk factors affecting glue
      assisted closure (GAC) in the enterocutaneous fistula (ECF) patients receiving
      glue application. BACKGROUND: ECF is a challenging problem in surgical practice,
      and it is difficult to resolve by spontaneous closure. Currently, GAC is popular
      when treating fistulas, but data related to risk factors are limited. METHODS: We
      retrospectively analyzed 82 patients with 93 ECFs, who had autologous glue
      sealing from 2010 to 2012 in a referral center. Their demographic data, clinical
      records, and fistula characteristics were collected. Both univariate analysis and
      multivariate Cox proportional hazards model were used to determine the prognostic
      factors affecting closure. RESULTS: During the 14-day treatment period, 78.5%
      (73/93) of the fistulas achieved GAC. We excluded 3 reopened fistulas and
      investigated 90 ECFs from 79 patients. Univariate analysis demonstrated that
      patients with high levels of CRP, high CRP:prealbumin ratio, elevated blood
      glucose, and specific pathogen colonization, together with lower GI location,
      greater output volume, and shorter tract length, had a poor outcome (P<0.05).
      Using multivariate analysis, monomicrobial and polymicrobial colonization with
      Klebsiella pneumoniae inside the fistula tracts (hazard ratio, 0.191; 95%
      confidence interval, 0.045-0.810; P=0.025) was a statistically significant risk
      factor for failure of fistula closure. CONCLUSIONS: The presence of monomicrobial
      and polymicrobial colonization with K. pneumoniae in fistulous tracts was an
      independent risk factor for failure of GAC in patients receiving glue
      application. Better debridement of the tracts should be performed before the glue
      sealing.

PMID- 24440939
TI  - Long-term survival of fibrolamellar hepatocellular carcinoma versus conventional
      hepatocellular carcinoma: a US population-based study.

PMID- 24440940
TI  - Time trends of US hospitalization for esophageal disease.
AB  - BACKGROUND AND AIMS: The occurrence of reflux disease seems to be rising in the
      United States. The aim of the present study was to follow the time trends of
      hospitalization for gastroesophageal reflux disease (GERD) and other esophageal
      disease during the past 4 decades. METHODS: US hospital utilization data were
      available for individual years from 1970 to 2010 through the National Hospital
      Discharge Survey. Esophageal diagnoses were stratified by their ninth revision of
      the International Classification of Diseases codes. Annual hospitalizations were
      expressed as rates per 100,000 living US population. RESULTS: GERD was by far the
      most common esophageal disorder resulting in hospitalization. However, in only 5%
      of instances did GERD-related diagnoses constitute the primary cause of
      hospitalization. Between 1970 and 2010 the rates of GERD-related hospitalizations
      increased in an exponential manner almost 10-fold. This rise affected both sex
      and all age groups alike. A 3-fold rise was noted in hospitalizations for
      esophageal adenocarcinoma. Other esophageal diagnoses, such as achalasia,
      dyskinesia, or stricture were characterized by falling or stable trends.
      CONCLUSIONS: US hospitalization data show a continued exponential rise in the
      occurrence of GERD without any signs of leveling off. These trends are likely to
      represent ongoing changes in the underlying incidence and prevalence of the
      disease.

PMID- 24440941
TI  - Proteinuria can predict short-term prognosis in critically ill cirrhotic
      patients.
AB  - BACKGROUND AND AIM: Increasing evidence supports that proteinuria is a useful
      tool in several clinical situations. Cirrhotic patients with proteinuria admitted
      to intensive care units (ICUs) have high mortality rates. This study analyzed the
      outcomes of critically ill cirrhotic patients and determined the prognostic value
      of proteinuria. METHODS: A total of 230 cirrhotic patients were admitted to the
      ICU of a hospital in Taiwan between March 2008 and February 2011. We
      prospectively collected data, including demographic parameters and clinical
      characteristics, of patients on day 1 of admission to the ICU and analyzed these
      variables as predictors of mortality. RESULTS: The overall ICU, hospital, and 90
      day mortality rates were 54%, 60%, and 63%, respectively. The patients with
      proteinuria had higher rates of acute kidney injury (84% vs. 53%, P<0.001), ICU
      death (60% vs. 25%, P<0.001), and 90-day mortality (79% vs. 40%, P<0.001).
      Patients with proteinuria had a hazard ratio for 90-day mortality of 2.800
      (P<0.001; 95% CI, 1.927-4.069). Multivariate analysis showed that proteinuria and
      the Sequential Organ Failure Assessment score were predictors of short-term
      prognosis. CONCLUSIONS: Proteinuria in critically ill cirrhotic patients is
      associated with increased complications of liver cirrhosis, ICU mortality, and
      poor short-term prognosis.

PMID- 24440942
TI  - Gastrohepatic fistula as a complication of laparoscopic radiofrequency liver
      ablation in a patient with intrahepatic cholangiocarcinoma.

PMID- 24440943
TI  - Low awareness of nonalcoholic fatty liver disease among patients at high
      metabolic risk.
AB  - GOALS: To assess awareness of nonalcoholic fatty liver disease (NAFLD) as a
      disease entity among individuals with and without metabolic risk factors in an
      outpatient clinical setting, and to evaluate interest in patient-centered
      education on NAFLD. BACKGROUND: NAFLD is the most common chronic liver disease in
      the United States with up to 30% of the adult population affected. Individuals
      with metabolic risk factors, particularly, insulin resistance, diabetes, and
      overweight/obesity, have a high prevalence of NAFLD estimated up to 70%, yet
      little is known about the understanding and perceptions of NAFLD in these high
      risk patients. STUDY: A self-administered paper questionnaire was given to 368
      adult patients presenting to an outpatient endocrinology clinic from February
      2012 to October 2012. RESULTS: A total of 302 surveys were completed for a
      response rate of 82%. Overall, 18% of all respondents reported awareness of
      NAFLD. Even among patients with self-reported major risk factors for NAFLD
      (overweight/obese, insulin resistant, or both overweight/obese and insulin
      resistant), the rates of awareness of NAFLD were low (19%, 23%, and 24%,
      respectively). A majority of survey respondents expressed interest in receiving
      patient-centered education on NAFLD (73%). CONCLUSIONS: Among high metabolic risk
      individuals there is low awareness of NAFLD. The majority of those surveyed
      expressed interest in learning about NAFLD. These findings suggest opportunities
      to raise public awareness of NAFLD, particularly among patients at high metabolic
      risk, and to provide education to high-risk individuals with the goal of
      implementing early prevention strategies and optimizing care.

PMID- 24440944
TI  - Management of bleeding-associated severe gastritis of the gastric mucosa in a
      patient with a gastrocystoplasty.
AB  - Gastrocystoplasty is a form of bladder augmentation (neobladder), where a segment
      of the stomach is surgically attached to the urinary bladder to increase bladder
      capacity and compliance. Although bleeding and malignant complications of
      gastrocystoplasty have been reported, the risks of these complications in the
      setting of gastrocystoplasty are not known. We describe the case of a 58-year-old
      African American woman with a history of a congenital solitary kidney, chronic
      kidney disease, and status postgastrocystoplasty and catheterizable umbilical
      stoma 21 years ago for neurogenic bladder presented with gross hematuria. To the
      best of our knowledge, this is the first reported case of gastrocystoplasty with
      a bleeding complication that has endoscopic pictures before and after treatment
      with proton pump inhibitor. 

PMID- 24440945
TI  - pRNA: NoRC-associated RNA of rRNA operons.
AB  - Promoter-associated RNAs (pRNAs) are a family of ~90-100 nt-long divergent RNAs
      overlapping the promoter of the rRNA (rDNA) operon. pRNA transcripts interact
      with TIP5, a component of the chromatin remodeling complex NoRC, which recruits
      enzymes for heterochromatin formation and mediates silencing of rRNA genes. Here
      we present a comprehensive analysis of pRNA homologs, including different
      versions per species, as result of in silico studies in available metazoan genome
      assemblies. Comparative sequence analysis and secondary structure prediction
      ended up in two possible secondary structures, which let us assume a possible
      dual function of pRNAs for regulation of rRNA operons. Furthermore, we validated
      parts of our computational predictions experimentally by RT-PCR and sequencing. A
      representative seed alignment of the pRNA family, annotated with possible
      secondary structures was released to the Rfam database. 

PMID- 24440946
TI  - From the editor.

PMID- 24440947
TI  - Ergonomics and health care.
AB  - This article provides a brief history of the field of ergonomics and explores the
      interrelationship between health care and ergonomic professions. Health care
      practitioners contribute a unique perspective to an ergonomic research and
      intervention team. This singular perspective is based on knowledge of health
      issues, disease and injury etiology and prognosis, and the psychosocial impact of
      illness. Topics for collaboration between health care practitioners and
      ergonomists are identified. 

PMID- 24440948
TI  - Energy cost and efficiency of a demanding combined manual materials-handling
      task.
AB  - Energy cost and crew performance were studied during a 45-hour continuous field
      artillery loading exercise using a howitzer simulator. An interrupted peak
      <formula>$?dot{V}_{0_{2}}$</formula> test, conducted in the simulator, was used
      to develop individualized equations to predict energy cost from heart rate. Nine
      experienced crew members rotated through six 1.5-hour loading cycles. Mission
      time (the time elapsed from the order to fire until task completion) was recorded
      and summed over cycles. Measures made at the end of each cycle included profile
      of mood state (POMS); rating of perceived exertion (RPE); rating of pain,
      soreness, and discomfort (RPSD); and isometric hand-grip strength. Results showed
      a significant decrease (p<0.01) in energy cost (8.0-6.2 kcal.min-1) and mission
      time (28.1-24.3 min) from Cycle 1 to Cycle 6. The POMS revealed an increase in
      fatigue and tension and a decrease in vigor (p<0.05); RPE increased (p<0.05) over
      time as did RPSD reported for the shoulders, arms, and hands (p<0.05). Isometric
      hand-grip strength decreased 8.6% (p<0.05) from Cycle 1 to Cycle 6. The
      efficiency of howitzer loading performance increased; however, the changes in
      RPE, POMS, hand-grip, and RPSD suggest that longer duration exercises may result
      in performance decrements. These data indicate that simulators can improve the
      performance of this task. 

PMID- 24440949
TI  - Occupational Therapists Whose Primary Area of Practice Is Hand TherapySelf
      Reported Cumulative Trauma Disorders.
AB  - Hand therapists perform hand-intensive work and engage in tasks that require
      movements and postures cited in the literature to be risk factors for the
      development of cumulative trauma disorders. This study was conducted to determine
      the incidence, prevalence, and types of work-related cumulative trauma disorders
      of the hand, wrist, and elbow experienced by occupational therapists whose
      primary area of practice is hand therapy. A survey was sent to a national random
      sample of 289 occupational therapists, 227 of whom responded. A total of 328
      upper-extremity injuries/syndromes were reported by 165 (79 %) of the
      respondents; 62 % of those injuries occurred as a result of cumulative work
      trauma. This study identified hand therapy as another occupation where cumulative
      trauma disorders are common. It is crucial that hand therapists become cognizant
      of their occupational risks and limitations so that such painful and disabling
      conditions can be prevented. 

PMID- 24440950
TI  - Cumulative Trauma Disorders and ErgonomicsA Vendor's Perspective.
AB  - By tracing office (computer-related) trends from the 1960s through the 1990s, one
      can extract the reasons for the dramatic rise in workplace injuries that result
      from poor ergonomic conditions. Much confusion continues to exist surrounding the
      notion of ergonomics, and employers are afraid to plunge in and implement an
      ergonomic program. Ergonomists have highlighted three key areas for
      consideration: motion/exercise, support, and neutral positioning. This article
      examines several products that meet those recommendations and promote proper work
      habits. 

PMID- 24440951
TI  - Role of Wrist Immobilization in the Work EnvironmentErgonomics and Carpal Tunnel
      Syndrome.
AB  - Commercial wrist splints do not constitute an ergonomic control for stressors
      associated with carpal tunnel syndrome. The science of ergonomics seeks to change
      the environment, not the human, in an effort to fit the work requirements to the
      capabilities of the individual. In contrast, immobilization of the wrist seeks to
      change the worker while the work environment exposures remain unchanged. Given
      this caveat, do wrist splints play a preventive role in the work environment with
      respect to the control of physical stressors that are likely to cause or
      exacerbate carpal tunnel syndrome? In an effort to provide an answer to this
      question, this article will provide a short synopsis of carpal tunnel syndrome as
      it relates to its diagnosis, occurrence in industry, and conservative treatment;
      a brief review of splinting as conservative treatment and an overview of the
      effect of wrist immobilization on physical stressors. 

PMID- 24440952
TI  - Participatory ErgonomicsA Group Dynamics Perspective.
AB  - Participatory ergonomics is a relatively new strategy employed by work-injury
      management professionals to effect organizational change and reduce workplace
      injuries. This method is based on group dynamics theory involving employee and
      management participation in decision making. A review of the literature on the
      properties of participation suggests that the most effective strategy for
      participation is one that incorporates informal, direct, high-access, and long
      term aspects. The ergonomic consultant must review participation as a concept
      that takes on different meanings depending upon the properties emphasized and the
      context in which it is implemented. 

PMID- 24440953
TI  - Prediction of performance on two stretcher-carry tasks.
AB  - Pre-placement screening for physically demanding jobs should result in better job
      performance and fewer injuries, if the test components reflect job demands. The
      purpose of this study was to determine how seven strength measures, three Army
      Physical Fitness Test (APFT) scores, and three physical descriptors relate to
      performance on two stretcher-carry tasks: 1) a repeated short-distance carry and
      2) a continuous long-distance carry. Twelve men and 11 women completed both tasks
      with and without (hand-carry) a shoulder harness. Pearson product moment
      correlation coefficients compared independent variables and forward stepwise
      multiple regression analyses were used for predictions. For repeated short
      distance stretcher-carrying, two-mile run time and handgrip were the best
      predictors of performance (hand-carry: r2=0.79, p<0.01; harness-carry: r2=0.75,
      p<0.01). The grip, which was more predictive during the hand-carry, required a
      sudden maximal contraction to peak force, followed by immediate release, while a
      sudden maximal contraction to peak force maintained for four seconds, was more
      predictive of the harness-carry. For the continuous hand-carry, the best
      predictor was a gradual buildup to a 6-second sustained grip strength (r2=0.74,
      p<0.01). These results illustrate the necessity for tailoring preplacement tests
      to accurately reflect job demands. 

PMID- 24440954
TI  - Certification in ErgonomicsAn Update and Commentary.
AB  - This article is an information update on certification in the practice of
      ergonomics. Ergonomic certification is currently being conducted by the Board of
      Certification in Professional Ergonomics for ergonomics/human factors
      practitioners. Ergonomic certification is also being discussed as a possibility
      for health care professionals by the National Interdisciplinary Committee on
      Health Ergonomics and the Medical Ergonomics Society. 

PMID- 24440955
TI  - Home automation in the workplace.
AB  - Environmental control units and home automation devices contribute to the
      independence and potential of individuals with disabilities, both at work and at
      home. Devices currently exist that can assist people with physical, cognitive,
      and sensory disabilities to control lighting, appliances, temperature, security,
      and telephone communications. This article highlights several possible
      applications for these technologies and discusses emerging technologies that will
      increase the benefits these devices offer people with disabilities. 

PMID- 24440956
TI  - A MET Isn't Just a Baseball Player from New York.
AB  - Most of us hold opinions on contemporary issues in work practice, in all its
      broad dimensions. "Sounding Board" is a regular feature of this publication,
      designed to provide a forum for expressing such views, whether mainstream or
      controversial.The opinions expressed in this section may not necessarily
      represent the views of the editor, the publisher, or the editorial board but are
      intended to stimulate discussion or to provoke a response. Readers who wish to
      comment on the ideas put forth in "Sounding Board" should address their comments
      to the editor. 

PMID- 24440957
TI  - SMART-LiftSM.

PMID- 24440959
TI  - N-oxide reduction of quinoxaline-1,4-dioxides catalyzed by porcine aldehyde
      oxidase SsAOX1.
AB  - Quinoxaline-1,4-dioxides (QdNOs) are a class of quinoxaline derivatives that are
      widely used in humans or animals as drugs or feed additives. However, the
      metabolic mechanism, especially the involved enzymes, has not been reported in
      detail. In this study, the N-oxide reduction enzyme, porcine aldehyde oxidase
      SsAOX1 was identified and characterized. The SsAOX1 gene was cloned from pig
      liver through reverse-transcription polymerase chain reaction using degenerate
      primers, which encode a 147-kDa protein with typical aldehyde oxidase motifs, two
      [2Fe-2S] centers, a flavin adenine dinucleotide (FAD) binding domain, and a
      molybdenum cofactor domain. After heterologous expression in a prokaryote,
      purified SsAOX1 formed a functional homodimer under native conditions.
      Importantly, the SsAOX1 catalyzed the N-oxide reduction at the N1 position of
      three representative QdNOs (quinocetone, mequindox, and cyadox), which are
      commonly used as animal feed additives. SsAOX1 has the highest activity toward
      quinocetone, followed by mequindox and cyadox, with kcat/K(m) values of 1.94 +/-
      0.04, 1.27 +/- 0.15, and 0.43 +/- 0.09 minute(-1) MUM(-1), respectively. However,
      SsAOX1 has the lowest substrate affinity for quinocetone, followed by the cyadox
      and mequindox, with K(m) values of 4.36 +/- 0.56, 3.16 +/- 0.48, and 2.96 +/-
      0.51 MUM, respectively. In addition, using site-directed mutagenesis, we found
      that substitution of glycine 1019 with threonine endows SsAOX1 with N-oxide
      reductive activity at the N4 position. The goal of this study was to identify and
      characterize the N-oxide reduction enzyme for a class of veterinary drugs, QdNOs,
      which will aid in the elucidation of the metabolic pathways of QdNOs and will
      provide a theoretical basis for their administration and new veterinary drug
      design.

PMID- 24440960
TI  - Interaction of novel platelet-increasing agent eltrombopag with rosuvastatin via
      breast cancer resistance protein in humans.
AB  - Eltrombopag (ELT), an orally available thrombopoietin receptor agonist, is a
      substrate of organic anion transporting polypeptide 1B1 (OATP1B1), and
      coadministration of ELT increases the plasma concentration of rosuvastatin in
      humans. Since the pharmacokinetic mechanism(s) of the interaction is unknown, the
      present study aimed to clarify the drug interaction potential of ELT at
      transporters. The OATP1B1-mediated uptake of ELT was inhibited by several
      therapeutic agents used to treat lifestyle diseases. Among them, rosuvastatin was
      a potent inhibitor with an IC(50) of 0.05 uM, which corresponds to one-seventh of
      the calculated maximum unbound rosuvastatin concentration at the inlet to the
      liver. Nevertheless, a simulation study using a physiologically based
      pharmacokinetic model predicted that the effect of rosuvastatin on the
      pharmacokinetic profile of ELT in vivo would be minimal. On the other hand, ELT
      potently inhibited uptake of rosuvastatin by OATP1B1 and human hepatocytes, with
      an IC(50) of 0.1 uM. However, the results of the simulation study indicated that
      inhibition of OATP1B1 by ELT can only partially explain the clinically observed
      interaction with rosuvastatin. ELT also inhibited transcellular transport of
      rosuvastatin in MDCKII cells stably expressing breast cancer resistance protein
      (BCRP), and was found to be a substrate of BCRP. The interaction of ELT with
      rosuvastatin can be almost quantitatively explained on the assumption that
      intestinal secretion of rosuvastatin is essentially completely inhibited by ELT.
      These results suggest that BCRP in small intestine may be the major target for
      interaction between ELT and rosuvastatin in humans.

PMID- 24440961
TI  - Properties of an almost localized Fermi liquid in an applied magnetic field
      revisited: a statistically consistent Gutzwiller approach.
AB  - We discuss the Hubbard model in an applied magnetic field and analyze the
      properties of neutral spin-[Formula: see text] fermions within the so-called
      statistically consistent Gutzwiller approximation. The magnetization curve
      reproduces in a semiquantitative manner the experimental data for liquid (3)He in
      the regime of moderate correlations and in the presence of a small number of
      vacant cells, modeled by a non-half-filled band situation, when a small number of
      vacancies (~5%) is introduced in the virtual fcc lattice. We also present the
      results for the magnetic susceptibility and the specific heat, in which a
      metamagnetic-like behavior is also singled out in a non-half-filled band case. 

PMID- 24440962
TI  - Molecular characterization and expression patterns of myogenin in compensatory
      growth of Megalobrama amblycephala.
AB  - Myogenin (myog) is a muscle-specific basic helix-loop-helix (bHLH) transcription
      factor that plays an essential role in regulating skeletal muscle development and
      growth. To investigate molecular characterization of myog and the effect of
      starvation/refeeding on the gene expression, we isolated the myog cDNA sequence
      and analyzed the expression patterns using quantitative real-time polymerase
      chain reaction in Megalobrama amblycephala. Sequence analysis indicated that M.
      amblycephala myog shared an analogous structure with the highly conserved His/Cys
      rich, bHLH and C-terminal helix III domains with other vertebrates. Sequence
      alignment and phylogenetic tree showed that M. amblycephala myog had the highest
      identity with the homologues of Ctenopharyngodon idella and Cyprinus carpio.
      Spatio-temporal expression patterns revealed that myog mRNA levels at the
      segmentation period and 12 h post-hatching (hph) were significantly higher than
      at other development stages (P<0.05). Furthermore, the highest myog expression
      level was predominantly observed in white muscle compared with the other types of
      muscle. Fish body weight continuously decreased during 21-day starvation and then
      significantly increased after 7days of refeeding and reached the similar level to
      the control at 21days of refeeding, indicating that the pattern of complete
      compensatory growth possibly occurred in M. amblycephala; meanwhile, the relative
      somatic growth rate after refeeding was also dramatically higher than the control
      group. In addition, the myog expression decreased during 21days of starvation and
      then exhibited a strong rebound effect after 7days of refeeding and subsequently
      declined gradually to the control level by 21days of refeeding. 

PMID- 24440963
TI  - Dietary CdSe/ZnS quantum dot exposure in estuarine fish: bioavailability,
      oxidative stress responses, reproduction, and maternal transfer.
AB  - Continued development, use, and disposal of quantum dots (QDs) ensure their
      entrance into aquatic environments where they could pose a risk to biological
      organisms as whole nanoparticles or as degraded metal constituents. Reproductive
      Fundulus heteroclitus were fed a control diet with lecithin, diets containing 1
      or 10 MUg of lecithin-encapsulated CdSe/ZnS QD/day, or a diet containing 5.9 MUg
      CdCl2/day for 85 days. Cadmium concentrations in liver, intestine, and eggs were
      quantified with inductively coupled plasma mass spectrometry. In fish fed 10 MUg
      QD/day, QDs or their degradation products traversed the intestinal epithelia and
      accumulated in the liver. Less than 0.01% of the QD's cadmium was retained in the
      liver or intestinal tissues. This compares to 0.9% and 0.5% of the cadmium in the
      intestine and liver, respectively of fish fed a CdCl2 diet. Cadmium was also
      detected in the eggs from parents fed 10 MUg QD/day. No significant changes in
      hepatic total glutathione, lipid peroxidation, or expression of genes involved in
      metal metabolism or oxidative stress were observed. While QDs in the diet are
      minimally bioavailable, unusual levels of vitellogenin transcription in male fish
      as well as declining fecundity require further investigation to determine if
      endocrine disruption is of environmental concern.

PMID- 24440965
TI  - Exploratory modeling and simulation to support development of motesanib in Asian
      patients with non-small cell lung cancer based on MONET1 study results.
AB  - The motesanib phase III MONET1 study failed to show improvement in overall
      survival (OS) in non-small cell lung cancer, but a subpopulation of Asian
      patients had a favorable outcome. We performed exploratory modeling and
      simulations based on MONET1 data to support further development of motesanib in
      Asian patients. A model-based estimate of time to tumor growth was the best of
      tested tumor size response metrics in a multivariate OS model (P < 0.00001) to
      capture treatment effect (hazard ratio, HR) in Asian patients. Significant
      independent prognostic factors for OS were baseline tumor size (P < 0.0001),
      smoking history (P < 0.0001), and ethnicity (P < 0.00001). The model successfully
      predicted OS distributions and HR in the full population and in Asian patients.
      Simulations indicated that a phase III study in 500 Asian patients would exceed
      80% power to confirm superior efficacy of motesanib combination therapy (expected
      HR: 0.74), suggesting that motesanib combination therapy may benefit Asian
      patients. 

PMID- 24440964
TI  - Multigenerational effects of benzo[a]pyrene exposure on survival and
      developmental deformities in zebrafish larvae.
AB  - In the aquatic environment, adverse outcomes from dietary polycyclic aromatic
      hydrocarbon (PAH) exposure are poorly understood, and multigenerational
      developmental effects following exposure to PAHs are in need of exploration.
      Benzo[a]pyrene (BaP), a model PAH, is a recognized carcinogen and endocrine
      disruptor. Here adult zebrafish (F0) were fed 0, 10, 114, or 1,012 MUg BaP/g diet
      at a feed rate of 1% body weight twice/day for 21 days. Eggs were collected and
      embryos (F1) were raised to assess mortality and time to hatch at 24, 32, 48, 56,
      72, 80, and 96 h post fertilization (hpf) before scoring developmental
      deformities at 96 hpf. F1 generation fish were raised to produce the F2
      generation followed by the F3 and F4 generations. Mortality significantly
      increased in the higher dose groups of BaP (2.3 and 20 MUg BaP/g fish) in the F1
      generation while there were no differences in the F2, F3, or F4 generations. In
      addition, premature hatching was observed among the surviving fish in the higher
      dose of the F1 generation, but no differences were found in the F2 and F3
      generations. While only the adult F0 generation was BaP-treated, this exposure
      resulted in multigenerational phenotypic impacts on at least two generations (F1
      and F2). Body morphology deformities (shape of body, tail, and pectoral fins)
      were the most severe abnormality observed, and these were most extreme in the F1
      generation but still present in the F2 but not F3 generations. Craniofacial
      structures (length of brain regions, size of optic and otic vesicles, and jaw
      deformities), although not significantly affected in the F1 generation, emerged
      as significant deformities in the F2 generation. Future work will attempt to
      molecularly anchor the persistent multigenerational phenotypic deformities noted
      in this study caused by BaP exposure.

PMID- 24440966
TI  - Pharmacotherapy in cancer patients with HIV/AIDS.
AB  - Antiretroviral therapy (ART) has significantly reduced morbidity and increased
      life expectancy of individuals infected with human immunodeficiency virus (HIV).
      Consequently, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies
      are increasing in frequency, which necessitates the concurrent use of
      antineoplastics and ART. Although drug interactions are a major concern when
      combining these agents, there is currently limited guidance on dose adjustments
      required to maintain safe and efficacious drug exposure. 

PMID- 24440968
TI  - Salmonella vaccines: lessons from the mouse model or bad teaching?
AB  - Salmonella enterica subsp. enterica includes several very important human
      serovars including Typhi, Paratyphi, Typhimurium and Enteritidis. These bacteria
      cause a significant global burden of disease, typically classified into enteric
      fever, gastroenteritis and, more recently, invasive non-typhoidal salmonellosis
      (iNTS). Vaccines have been developed for one of these serovars, S. Typhi and the
      recent increase in iNTS cases has resulted in a push to develop new vaccines that
      will inhibit disease by S. Typhimurium and S. Enteritidis, the most common iNTS
      S. enterica serovars. The development of new human vaccines has been informed by
      studies in the murine model of typhoid fever based on S. Typhimurium infections
      of very 'sensitive' (Nramp-1(S)) mice, which has some obvious deficiencies, not
      the least that antibodies protect humans against S. Typhi infection but are only
      weakly protective in 'sensitive' mice infected with S. Typhimurium. S.
      Typhimurium also lacks Vi, the target of protective antibodies in typhoid fever.
      Notwithstanding these deficiencies, the murine model has identified a very
      complex series of innate and adaptive immune responses to infection that might be
      exploited to develop new vaccines. Equally, advances in understanding the
      pathogenesis of infection, through pathogenomics and more sophisticated animal
      models will likely contribute to the development of novel immunogens. 

PMID- 24440967
TI  - Genetic influences on receptive joint attention in chimpanzees (Pan troglodytes).
AB  - Despite their genetic similarity to humans, our understanding of the role of
      genes on cognitive traits in chimpanzees remains virtually unexplored. Here, we
      examined the relationship between genetic variation in the arginine vasopressin
      V1a receptor gene (AVPR1A) and social cognition in chimpanzees. Studies have
      shown that chimpanzees are polymorphic for a deletion in a sequence in the 5'
      flanking region of the AVPR1A, DupB, which contains the variable RS3 repetitive
      element, which has been associated with variation in social behavior in humans.
      Results revealed that performance on the social cognition task was significantly
      heritable. Furthermore, males with one DupB(+) allele performed significantly
      better and were more responsive to socio-communicative cues than males homozygous
      for the DupB- deletion. Performance on a non-social cognition task was not
      associated with the AVPR1A genotype. The collective findings show that AVPR1A
      polymorphisms are associated with individual differences in performance on a
      receptive joint attention task in chimpanzees. 

PMID- 24440969
TI  - The effects of exercise training on levels of vascular endothelial growth factor
      in tumor-bearing mice.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) affects tumor growth and
      metastasis by mediating angiogenesis. Vascular endothelial growth factor
      overexpression is considered a predictor of poor prognosis in cancer patients.
      Exercise may increase the circulating levels of VEGF, which is important to
      angiogenesis. We examined the effects of exercise training on VEGF levels and
      tumor growth in male C57BL/6 mice inoculated with Lewis lung cancer cells.
      METHODS: Thirty-two mice were randomly assigned to either the tumor control (TC,
      n=16) group or the tumor exercise (TE, n=16) group. Half of the mice in TE group
      received aerobic interval exercise training, and the other half received aerobic
      continuous exercise training for 4 weeks. The animal weights and tumor volumes
      were assessed three times per week. Serum VEGF levels were determined at
      baseline, 2 and 4 weeks. The solid tumor, lung and liver were excised and
      evaluated at study completion. RESULTS: There was a significant increase in VEGF
      levels after the 4-week exercise training program in TE group, but no significant
      changes were observed in TC group. CONCLUSIONS: Although exercise training
      increased serum VEGF levels, group differences were not evident in our study.
      Exercise training did not alter the survival rate or tumor growth in tumor
      bearing mice.

PMID- 24440970
TI  - Overexpression of PIWI proteins in human stage III epithelial ovarian cancer with
      lymph node metastasis.
AB  - BACKGROUND: PIWI proteins belong to the Argonaute family. The human PIWI
      subfamily genes encode four PIWI (also known as PIWI-like) proteins: PIWIL1,
      PIWIL2, PIWIL3, and PIWIL4. The dysregulated expression of PIWI proteins appears
      to be associated with tumorigenesis. OBJECTIVE: To explore the expression of PIWI
      proteins in primary and metastatic tumors from patients with stage III epithelial
      ovarian cancer (EOC), evaluate the diagnostic value of PIWI in various tissues,
      and analyze the characteristics of each PIWI protein associated with metastasis.
      METHODS: A total of 20 patients with stage III EOC were retrieved for the present
      study. Various tissues from the primary tumor, adjacent normal tissue, peritoneal
      metastasis, and lymph node with or without metastasis were examined. PIWI
      proteins were detected by immunohistochemistry using tissue microarray and
      analyzed. RESULTS: PIWIL1, PIWIL2, PlWlL3, and PIWIL4 were expressed in EOC. By
      comparison with the adjacent normal tissues, the expression of four PIWI proteins
      was significantly enhanced in the primary tumor and metastatic tissues (P< 0.01).
      CONCLUSION: PIWI proteins are upregulated in EOC and associated with metastasis.
      These proteins may be useful as diagnostic biomarkers for EOC. The function of
      PIWI proteins in EOC with tumor metastasis will need to be further explored.

PMID- 24440971
TI  - Overexpression of integrin alphav in the human nasopharyngeal carcinoma
      associated with metastasis and progression.
AB  - BACKGROUND: Integrins are cell-surface adhesion molecules, regulate normal
      cellular interactions, and which are consisting of alpha and beta subunits and
      facilitate signal transduction in a bidirectional manner. Tumor cells have been
      found to express a wide variety of integrins, overexpression of integrin alphav
      has been detected in a growing number of human malignancy types, However, the
      reports obout expression of integrin alphav in nasopharyngeal carcinoma (NPC) are
      very rare. OBJECTIVE: This study aims to detect the expression of integrin alphav
      in NPC, and to evaluate the correlation between integrin alphav expression and
      clinicopathological factors. METHODS: Real-time polymerase chain reaction (real
      time PCR) assay and immunohistochemical staining were performed to detect the
      expression of integrin alphav in NPC tissue samples. The correlation between the
      integrin alphav expression and clinicopathological factors was evaluated.
      RESULTS: In NPC tissues, the expression levels of integrin alphav mRNA was
      significantly higher than those in the nasopharyngeal inflammation tissues (P<
      0.05), and the expression level were significantly correlated with T, N and
      clinical stage (all P < 0.05). Moreover, the expression rates of integrin alphav
      protein in NPC tissues was 76.92%, significantly higher than that of
      nasopharyngeal inflammation tissues (6.25%, P< 0.05). We also observed that the
      protein expression of integrin alphav was significantly related to T, N and
      clinical stage (all P< 0.05). CONCLUSIONS: All these findings suggest that
      overexpression of integrin alphav is closely associated with metastasis and
      progression of NPC. Therefore, we can speculate that integrin alphav could be
      effective prognostic markers in the future for individualized treatment of
      patients with NPC.

PMID- 24440972
TI  - Integrin beta 1 enhances the epithelial-mesenchymal transition in association
      with gefitinib resistance of non-small cell lung cancer.
AB  - We have previously shown that integrinbeta1 associates with gefitinib resistance.
      As epithelial-mesenchymal transition (EMT) also induces gefitinib resistance in
      vitro, we wished to determine the relation of them in gefitinib resistance. In
      this study, we show that integrinbeta1 induced epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitor (TKI) resistance in xenograft tumors and
      gefitinib-resistant NSCLC tumors acquired EMT phenotype. Furthermore, inhibition
      of integrinbeta1 reverses EMT, meanwhile overexpression and activation of
      integrinbeta1 aggravates EMT. Lastly, we further identified that integrinbeta1
      enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel
      relation of integrinbeta1 and EMT in EGFR TKI resistant NSCLC. 

PMID- 24440973
TI  - Carcinoembryonic antigen as prognostic factor for metastatic non-small cell lung
      cancer by percutaneous cryosurgery.
AB  - Carcinoembryonic antigen (CEA) is a prognostic marker for early-stage non-small
      cell lung cancer (NSCLC), and cryoablation is a new therapeutic alternative for
      lung cancer. We determined whether cryoablation-induced changes in serum CEA
      levels correlated with tumor type (adenocarcinoma or squamous carcinoma) and
      treatment type (comprehensive therapy [cryoablation of all intra- and
      extrapulmonary tumors] or palliative therapy [cryoablation of only extrapulmonary
      tumors]) in patients with metastatic NSCLC, and assessed whether pre-treatment
      CEA levels predicted overall survival (OS). We retrospectively reviewed the
      clinical data of 88 patients with metastatic NSCLC who underwent comprehensive
      (62 patients) or palliative (26 patients) therapy. Pre- and post-cryoablation
      serum CEA levels and overall survival were determined for all patients.
      Cryoablation significantly reduced CEA levels in adenocarcinoma, but not squamous
      carcinoma, patients. Among adenocarcinoma patients, the cryoablation-induced
      reduction in CEA levels was significantly greater after comprehensive treatment
      than after palliative treatment; the OS of patients under comprehensive
      cryoablation was longer than those under palliative treatment. Among
      adenocarcinoma patients receiving comprehensive cryoablation, OS was
      significantly longer in those with normal pre-treatment serum CEA levels than in
      those with abnormal pre-treatment serum CEA levels. Pretreatment level and change
      of serum CEA can be a good indicator for therapeutic effects and OS in metastatic
      NSCLC patients under percutaneous cryosurgery. 

PMID- 24440974
TI  - Selection of reference genes for RT-qPCR analysis in tumor tissues from male
      hepatocellular carcinoma patients with hepatitis B infection and cirrhosis.
AB  - BACKGROUND: Reverse transcription quantitative real-time polymerase chain
      reaction (RT-qPCR) has been widely used to quantify relative gene expression
      because of the high specificity, sensitivity and accuracy of this technique.
      However, its reliability is strongly depends on the expression stability of
      reference gene used for data normalization. Therefore, identification of reliable
      and condition specific reference genes is critical for the success of RT-qPCR.
      OBJECTIVE: Hepatitis B virus (HBV) infection, male gender and the presence of
      cirrhosis are widely recognized as the leading independent risk factors for the
      development of hepatocellular carcinoma (HCC). This study aimed to select
      reliable reference gene for RT-qPCR analysis in HCC patients with all of those
      risk factors. METHODS: Six candidate reference genes were analyzed in 33 paired
      tumor and non-tumor tissues from untreated HCC patients. The genes expression
      stabilities were assessed by geNorm and NormFinder. RESULTS: C-terminal binding
      protein 1(CTBP1) was the most stable gene among the 6 candidate genes evaluated
      by both geNorm and NormFinder. The expression stability values were 0.08 for
      CTBP1 and UBC, 0.09 for HPRT1, 0.12 for HMBS, 0.14 for GAPDH and 0.18 for 18S
      with geNorm analysis. The stability values suggested by NormFinder software were
      CTBP1: 0.044, UBC: 0.063, HMBS: 0.072, HPRT1: 0.072, GAPDH: 0.098 and 18S rRNA:
      0.161. CONCLUSION: This is the first systematic analysis which suggested CTBP1 as
      the highest expression-stable gene in human male HBV infection related-HCC with
      cirrhosis. We recommend CTBP1 as the best candidate reference gene when RT-qPCR
      was used to determine gene(s) expression in HCC. This may facilitate the relevant
      HBV related HCC studies in the future.

PMID- 24440975
TI  - Peripheral blood microvesicles are potential biomarkers for hepatocellular
      carcinoma.
AB  - BACKGROUND: Microvesicles (MVs) are produced through the outward vesicles budding
      and fission from the cell surface. Recently, it was discovered that extracellular
      MVs circulate in bodily fluids of cancer patients and could serve as potential
      diagnostic biomarkers. However, the diagnostic and prognostic roles of peripheral
      circulating MVs for hepatocellular carcinoma (HCC) remain unclear. OBJECTIVE: The
      aim of this study was to investigate whether the peripheral blood MVs could serve
      as potential biomarkers for detection of HCC. METHODS: Peripheral blood samples
      were obtained prior to treatment from 55 patients with HCC, 40 patients with
      liver cirrhosis and 21 healthy controls. MVs were isolated from peripheral blood
      by centrifugation and measured by using bicinchoninic acid assay. RESULTS:
      Peripheral blood MVs levels were significantly elevated in HCC patients compared
      to those in liver cirrhosis (p< 0.001). Furthermore, MVs levels was correlated
      with the HCC tumor size, pathological classification and TNM stage (p< 0.01). Of
      note, MVs levels were significantly reduced in the 1 month post-operative blood
      samples when compared to those in the pre-operative samples in the 17 HCC cases
      tested. MVs levels did not relate to liver enzymes, AFP levels, alcohol drinking
      or smoking habits (p> 0.05). In contrast, serum MVs levels correlated with the
      age of patients, leukocytes, platelets and prothrombin time. The results of
      receiver operating characteristic (ROC) analysis indicated better performance of
      MVs than AFP for early detection of HCC. The areas under the ROC curve of MVs for
      discriminating patients with early (TNM stage I) and relatively early (TNM stage
      II) HCC from liver cirrhosis was 0.83 (95% CI: 0.74-0.93) and 0.94 (95% CI: 0.88
      1.00), respectively. CONCLUSIONS: Peripheral blood MVs levels were increased in
      patients with HCC and associated with the progression of disease. Serum MVs might
      serve as novel biomarkers for the diagnosis of HCC at early stage.

PMID- 24440977
TI  - Identification of novel human glioblastoma-specific transcripts by serial
      analysis of gene expression data mining.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) remains the most common and aggressive
      primary brain tumor in adults with a poor median survival, and molecular
      biomarkers for GBM pathogenesis are in need. PURPOSE: The objective of this study
      is to identify potential novel genes for GBM pathogenesis by gene expression data
      mining. MATERIALS AND METHODS: Available SAGE libraries of GBM, astrocytoma, and
      normal brain tissues were collected from the Cancer Genome Anatomy Project
      (CGAP). Significance analysis for microarray (SAM) and CGAP-SAGE-Genie-DGED were
      used to identify differentially expressed tags, and specific tags that were
      differentially expressed only in GBM were further selected. Tags to genes
      association was performed by CGAP-SAGE-Genie-SAV. Immunohistochemistry was used
      to investigate distribution and validate expression of the interested gene.
      RESULTS: Three genes were significantly differentially expressed just in brain.
      up-regulated expression of STAB1 and down-regulated expression of SH3GL2 and
      DNM3. Immunohistochemistry assay indicated that STAB1 mainly expressed in
      vascular endothelial cells and over-expressed in GBM samples compared to normal
      samples. CONCLUSIONS: Our study shows that data mining of public sources of gene
      expression is an effective way to identify novel tumor-associated genes, and this
      work may contribute to the identification of candidate genes for GBM
      angiogenesis.

PMID- 24440976
TI  - Somatic gene mutations in African Americans may predict worse outcomes in
      colorectal cancer.
AB  - BACKGROUND AND OBJECTIVE: African Americans have worse outcomes in colorectal
      cancer (CRC) than Caucasians. We sought to determine if KRAS, BRAF and PIK3CA
      mutations might contribute to the racial differences in CRC outcome. METHODS: DNA
      was extracted from tissue microarrays made from CRC samples from 67 African
      Americans and 237 Caucasians. Mutations in KRAS, BRAF, and PIK3CA were evaluated
      by PCR sequencing. We also examined microsatellite instability (MSI) status.
      Associations of mutation status with tumor stage and grade were examined using a
      logistic regression model. Cox proportional hazards models were used to estimate
      the all-cause mortality associated with mutational status, race and other
      clinicopathologic features. RESULTS: KRAS mutations were more common in African
      Americans than among Caucasians (37% vs 21%, p=0.01) and were associated with
      advanced stage (unadjusted odds ratio (OR)=3.31, 95% confidence interval (CI)
      1.03-10.61) and grade (unadjusted OR=5.60, 95% CI 1.01-31.95) among African
      Americans. Presence of BRAF mutations was also positively associated with
      advanced tumor stage (adjusted OR=3.99, 95%CI 1.43-11.12) and grade (adjusted
      OR=3.93, 95%CI 1.05-14.69). PIK3CA mutations showed a trend toward an association
      with an increased risk of death compared to absence of those mutations (adjusted
      for age, sex and CRC site HR=1.89, 95% CI 0.98-3.65). Among African Americans,
      the association was more evident (adjusted for age, sex and CRC site HR=3.92, 95%
      CI 1.03-14.93) and remained significant after adjustment for MSI-H status and
      combined education-income level, with HR of 12.22 (95%CI 1.32-121.38).
      CONCLUSIONS: Our results suggest that African Americans may have different
      frequencies of somatic genetic alterations that may partially explain the worse
      prognosis among African Americans with CRC compared to whites.

PMID- 24440978
TI  - Mitochondrial uncoupling protein 2 is up-regulated in human head and neck, skin,
      pancreatic, and prostate tumors.
AB  - BACKGROUND: Mitochondrial uncoupling protein 2 (UCP2) uncouples electron
      transport from ATP production. UCP2 has been shown to play an important role in
      obesity and diabetes. Interestingly, studies have demonstrated that UCP2 is up
      regulated in human colon cancer samples. OBJECTIVE: In order to study the role of
      UCP2 in human cancers, we detected the UCP2 protein level in various human tumor
      tissues. METHODS: Six types of human tumor and adjacent normal tissue samples
      were collected and analyzed by Western blot assays to detect the levels of UCP2.
      RESULTS: The results showed that in the human head and neck, skin, prostate, and
      pancreatic tumor samples examined, the protein levels of UCP2 were significantly
      higher in tumor tissues than that in the adjacent normal tissues. The protein
      levels of UCP2 was lower in non-small cell lung tumor tissues, which is marginal
      significant. CONCLUSIONS: Over expression of UCP2 in certain tumors provides the
      rationale to speculate that UCP2 may promote tumor growth in these cancers.

PMID- 24440979
TI  - Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV
      detection in plasma.
AB  - BACKGROUND: The precise analysis of tumour markers in blood such as circulating
      cell-free DNA (cfDNA) could have a significant impact in facilitating monitoring
      of patients after initial therapy. Although high levels of total cfDNA in plasma
      of cancer patients are consistently demonstrated, a low sensitivity of DNA
      alterations is reported. OBJECTIVE: The major question regards the recovery of
      tumour-specific cfDNA such as KRAS mutated DNA and cancer-associated type 16 of
      human papillomavirus (HPV16). METHODS: TaqMan technology was used for detection
      of KRAS mutation, HPV16 and to quantify cfDNA in blood plasma. RESULTS:
      Comparison of four different column-based commercial kits shows that the cfDNA
      purification carried out by the Genomic Mini AX Body Fluids kit and the QIAamp
      Circulating Nucleic Acid kit gave us the possibility to improve the sensitivity
      of detection of KRAS mutation and HPV16. The optimized method was used to follow
      the reduction in cancer-specific cfDNA after therapy. We found that large volume
      extractions with low volume of DNA eluate enabled trace amounts of tumour
      specific cfDNA from cancer patients to be effectively identified. CONCLUSIONS:
      Data presented in this study facilitate detection of tumour-specific cfDNA and
      improve standards needed for the implementation of cfDNA technology into routine
      clinical practice.

PMID- 24440980
TI  - Searching for candidate microRNA biomarkers in detection of breast cancer: a meta
      analysis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are recognized as potential biomarkers for
      detection of breast cancer. Many experiments have been done to explore the
      aberrant expression of circulating miRNAs in breast cancer patients. However, an
      overwhelming number of miRNAs are identified and some expression characteristics
      are inconsistent between studies. OBJECTIVE: To distinguish the candidates for
      breast cancer detection from spurious miRNAs. METHODS: One solution is to take
      the intersections between studies. As repeated efforts can improve reliability
      and reduce error, valuable candidate miRNAs in this study are defined as those
      validated and consistently reported by multiple studies. Data validated by real
      time PCR (RT-PCR) were collected, and the most frequently reported miRNAs with
      consistent regulation were identified by using a vote-counting strategy based on
      the number of relevant studies, total sample size and fold change. RESULTS: The
      top four miRNAs (miR-21, -155, -222 and -10b) are consistently regulated in
      comparisons of the pre-operative patients and the control group. And blood sample
      type was found to affect the regulation characteristics of miRNAs. CONCLUSION:
      MiR-21, -155, -222 and -10b are reliable candidate biomarkers for detection of
      breast cancer.

PMID- 24440981
TI  - An unusual ischiorectal fossa mass.
AB  - INTRODUCTION: Peri-anal fistulae commonly present with collections requiring
      surgical intervention. The most common cause of a peri-anal mass is abscess
      formation secondary to anal gland sepsis. In certain patient groups such as those
      over 65 or with atypical presenting symptoms there are other important
      considerations. PRESENTATION OF CASE: A 70-year old male was referred by his
      general practitioner with symptoms of obstructed defaecation and a palpable mass
      in the ischiorectal fossa. He had previously undergone three operations for
      complex peri-anal fistulae in another hospital. Due to the previous history of
      surgery, seroma formation was considered and computed tomography guided drainage
      of the lesion was performed unsuccessfully. Given symptoms of obstructed
      defecation and need for histological diagnosis excision was undertaken. The
      approach was through a right pararectal incision over the bulk of the mass. Skin
      and pararectal tissue were divided revealing a mucinous lesion with multiple
      lobules adherent to pararectal tissue. Following histopathological examination a
      diagnosis of low grade mucinous neoplasm was made. DISCUSSION: Primary mucinous
      neoplasm in the ischiorectal fossa is very rare. Diagnostic criteria for
      adenocarcinoma arising from perianal fistulae have previously been established by
      Rosser et al. but this lesion does not fall into this category. It is categorised
      as a mucinous cystic neoplasm of uncertain malignant potential. The differential
      diagnoses are discussed. CONCLUSION: Consideration should be given to a range of
      pathologies in cases of atypical peri-anal masses.

PMID- 24440982
TI  - Splicing factor SRSF6 promotes hyperplasia of sensitized skin.
AB  - Many biological processes involve gene-expression regulation by alternative
      splicing. Here, we identify the splicing factor SRSF6 as a regulator of wound
      healing and tissue homeostasis in skin. We show that SRSF6 is a proto-oncogene
      frequently overexpressed in human skin cancer. Overexpressing it in transgenic
      mice induces hyperplasia of sensitized skin and promotes aberrant alternative
      splicing. We identify 139 SRSF6-target genes in skin and show that this SR-rich
      protein binds to alternative exons in the pre-mRNA of the extracellular-matrix
      protein tenascin C, thus promoting the expression of isoforms characteristic of
      invasive and metastatic cancer independently of cell type. SRSF6 overexpression
      additionally results in depletion of LGR6+ stem cells and excessive keratinocyte
      proliferation and response to injury. Furthermore, the effects of SRSF6 in wound
      healing assayed in vitro depend on the tenascin-C isoforms. Thus, abnormal SR
      protein expression can perturb tissue homeostasis. 

PMID- 24440984
TI  - Comparison of delayed matching-to-sample performance in monkeys and children.
AB  - Although research has consistently demonstrated that accuracy on a variety of
      memory tasks decreases as delay increases, relatively little research has been
      conducted to quantify this relationship across development in humans or directly
      compare rates of forgetting between humans and monkeys. This study utilized a
      delayed matching-to-sample (DMTS) task to compare the relative contributions of
      proactive interference and attention on the rate of forgetting in monkeys and
      children. The performance of 1125 children from four to fourteen years of age and
      10 adult rhesus monkeys was compared. For this DMTS task, a shape was displayed
      on the center one of three press-plates. After a delay, the subjects were
      required to match the original shape with one of three choice shapes to receive a
      banana-flavored food pellet for monkeys, or a nickel for children. A modified
      power function provided an excellent fit for the data for monkeys and children.
      The forgetting rates in children decreased with age, and the forgetting rates for
      monkeys were most comparable to those of younger children. The data also suggest
      that proactive interference did not significantly contribute to the forgetting
      rates for monkeys or younger children. Further, the monkeys appeared to attend to
      the task at a level similar to that of younger children as evidenced by the
      similarities in response latencies. The results from this study indicate that the
      rate of forgetting in monkeys, as well as the mechanisms underlying this rate,
      appears to share more similarities with that of younger children than of older
      children. 

PMID- 24440983
TI  - Competition between Grb2 and Plcgamma1 for FGFR2 regulates basal phospholipase
      activity and invasion.
AB  - FGFR2-expressing human cancer cells with low concentrations of the adaptor
      protein Grb2 show high prevalence for metastatic outcome. In nonstimulated cells,
      the SH3 domain (and not the SH2 domains) of Plcgamma1 directly competes for a
      binding site at the very C terminus of FGFR2 with the C-terminal SH3 domain of
      Grb2. Reduction of Grb2 concentration permits Plcgamma1 access to the receptor.
      Recruitment of Plcgamma1 in this way is sufficient to upregulate phospholipase
      activity. This results in elevated phosphatidylinositol 4,5-bisphosphate turnover
      and intracellular calcium levels, thus leading to increased cell motility and
      promotion of cell-invasive behavior in the absence of extracellular receptor
      stimulation. Therefore, metastatic outcome can be dictated by the constitutive
      competition between Grb2 and Plcgamma1 for the phosphorylation-independent
      binding site on FGFR2. 

PMID- 24440985
TI  - Sexy males and choosy females on exploded leks: correlates of male attractiveness
      in the Little Bustard.
AB  - In their choice of mates, females may use alternative tactics, including a
      comparative assessment of males in a population, using one or several relative
      preference criteria. Traits involved in female choice should presumably be
      variable between, but not within males, thus potentially providing reliable cues
      of male identity and quality for prospecting females. In lekking species, sexual
      selection is usually intense, and females can freely choose mates. Studying the
      Little Bustard Tetrax tetrax, a bird with an exploded lek mating system, we first
      identified male phenotypic traits that showed higher among, than within variation
      (plumage pattern, display rates and call structure). Among those and other traits
      (ornaments and their symmetry, body condition, lek spatial organization and
      territory quality), we identified phenotypic traits that correlated with male
      attractiveness toward females. At least four phenotypic male traits were
      correlated with female attraction, i.e. body condition, lek attendance,
      ornamental symmetry and display rates. Traits related to the initial female
      attraction on male territory seem to differ from traits related to the decision
      of females to stay in the territory of attractive males. 

PMID- 24440986
TI  - ClC-3 chloride channel/antiporter defect contributes to inflammatory bowel
      disease in humans and mice.
AB  - BACKGROUND: ClC-3 channel/antiporter plays a critical role in a variety of
      cellular activities. ClC-3 has been detected in the ileum and colon. OBJECTIVE:
      To determine the functions of ClC-3 in the gastrointestinal tract. DESIGN: After
      administration of dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic
      acid (TNBS), intestines from ClC-3-/- and wild-type mice were examined by
      histological, cellular, molecular and biochemical approaches. ClC-3 expression
      was determined by western blot and immunostaining. RESULTS: ClC-3 expression was
      reduced in intestinal tissues from patients with UC or Crohn's disease and from
      mice treated with DSS. Genetic deletion of ClC-3 increased the susceptibility of
      mice to DSS- or TNBS-induced experimental colitis and prevented intestinal
      recovery. ClC-3 deficiency promoted DSS-induced apoptosis of intestinal
      epithelial cells through the mitochondria pathway. ClC-3 interacts with voltage
      dependent anion channel 1, a key player in regulation of mitochondria cytochrome
      c release, but DSS treatment decreased this interaction. In addition, lack of ClC
      3 reduced the numbers of Paneth cells and impaired the expression of
      antimicrobial peptides. These alterations led to dysfunction of the epithelial
      barrier and invasion of commensal bacteria into the mucosa. CONCLUSIONS: A defect
      in ClC-3 may contribute to the pathogenesis of IBD by promoting intestinal
      epithelial cell apoptosis and Paneth cell loss, suggesting that modulation of ClC
      3 expression might be a new strategy for the treatment of IBD.

PMID- 24440988
TI  - Surgery rates in IBD.

PMID- 24440987
TI  - Cell cycle-related kinase mediates viral-host signalling to promote hepatitis B
      virus-associated hepatocarcinogenesis.
AB  - BACKGROUND: Androgen receptor (AR) signalling contributes to male predominance in
      hepatocellular carcinoma (HCC), which is more pronounced in HBV-endemic areas.
      Cell cycle-related kinase (CCRK) is essential for AR-induced hepatocarcinogenesis
      but its molecular function in HBV-associated HCC remains obscure. OBJECTIVE: To
      determine the molecular function of CCRK in HBV-associated HCC. DESIGN:
      Transcriptional regulation was assessed by chromatin immunoprecipitation,
      promoter mutation and luciferase reporter assays. Hepatocellular proliferation
      and tumourigenesis were examined by colony formation, soft agar assays and using
      HBV X protein (HBx) transgenic mice with low-dose exposure to diethylnitrosamine.
      Protein expressions were examined in clinical samples and correlated with patient
      survival by log-rank Mantel-Cox test. RESULTS: Overexpression of CCRK, but not
      its kinase-defective mutant, activated beta-catenin/T cell factor signalling
      through phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) at Ser9,
      led to upregulation of AR transcriptional activity and, subsequently, expression
      of HBx. The viral transactivator in turn induced CCRK expression through enhanced
      AR signalling, thus forming a positive regulatory loop. RNA interference
      silencing of CCRK, which suppressed the CCRK/GSK-3beta/beta-catenin/AR regulatory
      loop, significantly suppressed HBx-induced hepatocellular proliferation (p=0.001)
      and transformation (p<0.001) and remarkably reduced >80% diethylnitrosamine
      mediated hepatocarcinogenesis in HBx transgenic mice. Finally, patients with HBV
      associated HCC with concordant overexpression of CCRK, GSK-3beta phosphorylation
      at Ser9, active dephosphorylated beta-catenin and AR phosphorylation at Ser81 had
      poorer overall (HR=31.26, p<0.0001) and disease-free (HR=3.60, p<0.01) survival
      rates. CONCLUSIONS: Our findings highlight the critical role of CCRK in a self
      reinforcing circuitry that regulates HBV-associated hepatocarcinogenesis. Further
      characterisation of this intricate viral-host signalling may provide new
      prognostic biomarkers and therapeutic targets for HCC treatment.

PMID- 24440989
TI  - Don't panic: interpretation bias is predictive of new onsets of panic disorder.
AB  - Psychological models of panic disorder postulate that interpretation of ambiguous
      material as threatening is an important maintaining factor for the disorder.
      However, demonstrations of whether such a bias predicts onset of panic disorder
      are missing. In the present study, we used data from the Dresden Prediction
      Study, in which a epidemiologic sample of young German women was tested at two
      time points approximately 17 months apart, allowing the study of biased
      interpretation as a potential risk factor. At time point one, participants
      completed an Interpretation Questionnaire including two types of ambiguous
      scenarios: panic-related and general threat-related. Analyses revealed that a
      panic-related interpretation bias predicted onset of panic disorder, even after
      controlling for two established risk factors: anxiety sensitivity and fear of
      bodily sensations. This is the first prospective study demonstrating the
      incremental validity of interpretation bias as a predictor of panic disorder
      onset. 

PMID- 24440990
TI  - Relationship between noninvasive and invasive blood pressure values in end-stage
      renal disease patients on dialysis.
AB  - BACKGROUND: End-stage renal disease (ESRD) is complicated by high blood pressure
      (BP) and severe atherosclerosis, which may lead to different values of BP
      measured by invasive and noninvasive methods. However, the differences in BP
      values between these two methods and their possible mechanisms in ESRD have not
      been investigated. METHODS: Forty-one ESRD patients on dialysis were enrolled in
      the present study. Invasive BP, noninvasive BP, and carotid hemodynamic variables
      were obtained through radial artery catheterization, oscillometric methods, and
      echoarteriography, respectively. RESULTS: We found that noninvasive systolic BP
      (NISBP) was 30+/-20 mmHg (P<0.001) lower than invasive systolic BP (INSBP),
      whereas no significant difference was found in diastolic BP between these two
      methods. The difference between INSBP and NISBP was correlated with carotid peak
      systolic velocity (r=0.3550, P=0.0229). CONCLUSION: NISBP could not accurately
      represent INSBP in ESRD patients on dialysis. The lack of dynamic pressure
      measurement during NISBP measurement may contribute to the difference between
      NISBP and INSBP.

PMID- 24440993
TI  - Challenges in hypertension: prevalence, definition, mechanisms and management.

PMID- 24440992
TI  - Expression of cannabinoid receptor 2 and its inhibitory effects on synovial
      fibroblasts in rheumatoid arthritis.
AB  - OBJECTIVE: Recent studies have suggested immunomodulatory and anti-inflammatory
      effects of cannabinoid receptor 2 (CB2R) activation, which shows no
      psychoactivity. However, it is still unclear whether CB2R is expressed in
      fibroblast-like synoviocytes (FLS) of RA. In this study we investigated whether
      CB2R is expressed in FLS of RA, and whether CB2R activation modulates the
      function of RA-FLS. METHODS: Expression of CB2R in synovial tissue and FLS was
      studied by immunohistochemistry, western blotting and RT-PCR. mRNA expression
      levels of CB2R, IL-6 and MMPs were analysed by quantitative real-time RT-PCR. The
      protein concentrations of IL-6 and MMPs in culture supernatants were determined
      by ELISA. The protein levels of signal transducing molecules were assayed by
      western blotting. RESULTS: Both mRNA and protein expression of CB2R were found in
      synovial tissue and cultured FLS with slightly higher levels in RA patients than
      in OA patients. In cultured RA-FLS, the expression level of CB2R was up-regulated
      by stimulation with IL-1beta, TNF-alpha or lipopolysaccharide. In vitro, HU-308,
      a selective CB2R agonist, inhibited IL-1beta-induced proliferation of RA-FLS as
      well as IL-1beta-induced production of MMP-3, MMP-13 and IL-6 in RA-FLS in a dose
      dependent manner. HU-308 also suppressed IL-1beta-induced activation of
      extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein
      kinase in FLS. CONCLUSION: In RA-FLS, proinflammatory mediators up-regulate the
      expression of CB2R, which negatively regulates the production of proinflammatory
      cytokines and MMPs. These data suggest that CB2R may be a potential therapeutic
      target of RA.

PMID- 24440991
TI  - Mucosal adjuvants for vaccines to control upper respiratory infections in the
      elderly.
AB  - Influenza virus and Streptococcus pneumoniae are two major pathogens that lead to
      significant morbidity and mortality in the elderly. Since both pathogens enter
      the host via the mucosa, especially the upper respiratory tract (URT), it is
      essential to elicit pathogen-specific secretory IgA (SIgA) antibody (Ab)
      responses at mucosal surfaces for defense of the elderly. However, as aging
      occurs, alterations in the mucosal immune system of older individuals result in a
      failure to induce SIgA Abs for protection from these infections. To overcome
      mucosal immunosenescence, we have developed a mucosal dendritic cell targeting,
      novel double adjuvant system which we show to be an attractive and effective
      immunological modulator. This system induces a more balanced Th1- and Th2-type
      cytokine response which supports both mucosal SIgA and systemic IgG1 and IgG2a Ab
      responses. Thus, adaptation of this adjuvant system to nasal vaccines for
      influenza virus and S. pneumoniae could successfully provide protection by
      supporting pathogen-specific SIgA Ab responses in the URT in the mouse model of
      aging. In summary, a double adjuvant system is considered to be an attractive and
      potentially important strategy for the future development of mucosal vaccines for
      the elderly. 

PMID- 24440994
TI  - Regulation of sPLA2-IID in Human Decidua: Insights Into the Complexity of the
      Prostaglandin Pathway in Labor.
AB  - Prostaglandins are implicated in the labor process, yet the precise role and
      regulation of the prostaglandin pathway remains to be elucidated. The first step
      in the pathway is cleavage of membrane phospholipids by phospholipase A2 (PLA2).
      Previous work demonstrated upregulation of secretory PLA2 (sPLA2)-IIA with labor
      in human myometrium, and recent evidence shows that there are numerous PLA2
      isoforms. The present study investigates the potential of additional sPLA2
      isoforms during pregnancy and labor. Real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR), Western blotting, and immunohistochemistry were used to
      determine sPLA2 expression and localization. Results show the presence of sPLA2
      IID in amnion, chorion, placenta, decidua, and myometrium. Expression of sPLA2
      IID in decidua was significantly decreased in term labor compared to nonlabor
      patients, whereas no significant labor-associated changes were observed in other
      gestational tissues. Secretory PLA2-IID was localized within chorion fibroblasts,
      placenta trophoblasts, decidual cells, and in myometrial smooth muscle cells. In
      primary decidual cell cultures, interleukin (IL) 10 (IL-10) increased sPLA2-IID
      messenger RNA (mRNA) expression, while IL-1beta had no effect on sPLA2-IID mRNA
      expression. In conclusion, decreased expression of sPLA2-IID in the decidua at
      labor indicates that it is unlikely to contribute to increased prostaglandin
      production during labor. However, increased expression of sPLA2-IID, induced by
      IL-10, suggests that sPLA2-IID may play an important anti-inflammatory role at
      the maternal-fetal interface. Nevertheless, precise functions of sPLA2-IID within
      the human uterus remain to be determined.

PMID- 24440995
TI  - Amniotic fluid metabolomic analysis in spontaneous preterm birth.
AB  - OBJECTIVE: To identify metabolic changes associated with early spontaneous
      preterm birth (PTB; <34 weeks) and term births, using high-throughput
      metabolomics of amniotic fluid (AF) in African American population. METHOD: In
      this study, AF samples retrieved from spontaneous PTB (<34 weeks [n = 25]) and
      normal term birth (n = 25) by transvaginal amniocentesis at the time of labor
      prior to delivery were subjected to metabolomics analysis. Equal volumes of
      samples were subjected to a standard solvent extraction method and analyzed using
      gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS.
      Biochemicals were identified through matching of ion features to a library of
      biochemical standards. After log transformation and imputation of minimum
      observed values for each compound, t test, correlation tests, and false discovery
      rate corrections were used to identify differentially regulated metabolites. Data
      were controlled for clinical/demographic variables and medication during
      pregnancy. RESULTS: Of 348 metabolites measured in AF samples, 121 metabolites
      had a gestational age effect and 116 differed significantly between PTB and term
      births. A majority of significantly altered metabolites could be classified into
      3 categories, namely, (1) liver function, (2) fatty acid and coenzyme A (CoA)
      metabolism, and (3) histidine metabolism. The signature of altered liver function
      was apparent in many cytochrome P450-related pathways including bile acids,
      steroids, xanthines, heme, and phase II detoxification of xenobiotics with the
      largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8
      fold more abundant in PTB. CONCLUSION: Global metabolic profiling of AF revealed
      alteration in hepatic metabolites involving xenobiotic detoxification and CoA
      metabolism in PTB. Maternal and/or fetal hepatic function differences may be
      developmentally related and its contribution PTB as a cause or effect of PTB is
      still unclear.

PMID- 24440996
TI  - First-Trimester Detection of Surface Abnormalities: A Comparison of 2- and 3
      Dimensional Ultrasound and 3-Dimensional Virtual Reality Ultrasound.
AB  - The aim was to determine the diagnostic performance of 3-dimensional virtual
      reality ultrasound (3D_VR_US) and conventional 2- and 3-dimensional ultrasound
      (2D/3D_US) for first-trimester detection of structural abnormalities. Forty-eight
      first trimester cases (gold standard available, 22 normal, 26 abnormal) were
      evaluated offline using both techniques by 5 experienced, blinded sonographers.
      In each case, we analyzed whether each organ category was correctly indicated as
      normal or abnormal and whether the specific diagnosis was correctly made.
      Sensitivity in terms of normal or abnormal was comparable for both techniques (P
      = .24). The general sensitivity for specific diagnoses was 62.6% using 3D_VR_US
      and 52.2% using 2D/3D_US (P = .075). The 3D_VR_US more often correctly diagnosed
      skeleton/limb malformations (36.7% vs 10%; P = .013). Mean evaluation time in
      3D_VR_US was 4:24 minutes and in 2D/3D_US 2:53 minutes (P < .001). General
      diagnostic performance of 3D_VR_US and 2D/3D_US apparently is comparable.
      Malformations of skeleton and limbs are more often detected using 3D_VR_US.
      Evaluation time is longer in 3D_VR_US.

PMID- 24440997
TI  - Ulipristal acetate: critical review about endometrial and ovulatory effects in
      emergency contraception.
AB  - The effectiveness of emergency contraception (EC) is usually estimated by
      comparing the number of observed pregnancies to that of expected pregnancies
      after unprotected intercourse. Second-generation selective progesterone receptors
      modulators have been developed and evaluated for EC use. Among these compounds,
      ulipristal acetate (UPA) has been proven to share the same antiprogestin activity
      as mifepristone, and as with mifepristone, UPA has been demonstrated to be
      effective up to 120 hours after unprotected intercourse. The UPA is more
      effective than levonorgestrel (LNG) in preventing the appearance of clinically
      evident pregnancies. The LNG delays ovulation only when taken at the beginning of
      the fertile period; taken later, it is ineffective on ovulation, while it has
      been proven to impair the subsequent luteal function. The effectiveness of LNG
      decreases as time elapses and is limited to 72 hours after unprotected
      intercourse. The UPA maintains consistent effectiveness for 5 days after
      unprotected intercourse, and this effectiveness is independent on which of these
      5 days it is taken. The ability of UPA to delay ovulation decreases progressively
      as ovulation approaches and is null at the time of the luteinizing hormone (LH)
      peak: 1 to 2 days before ovulation, UPA behaves as a placebo. The persistent
      effectiveness of the drug cannot be due to antiovulatory action, as it decreases
      sharply as LH approaches its peak level. The effectiveness is most likely due to
      the dramatic endometrial effects of the drug that are produced regardless of when
      it is taken. These effects are consistently present, as the threshold for
      altering endometrial morphology is lower than the threshold for altering
      folliculogenesis. 

PMID- 24440998
TI  - Long-Term Risk to Develop Hypertension in Women With Former Preeclampsia: A
      Longitudinal Pilot Study.
AB  - INTRODUCTION: Women with former preeclampsia (exPE) develop chronic hypertension
      4 times more often than healthy parous controls. Women, destined to develop
      remote chronic hypertension, had increased left ventricular mass index (LVMI) and
      diastolic blood pressure (BP) prior to the onset of hypertension as compared to
      those remaining normotensive. However, longitudinal data on the progress of this
      increased LVMI in women destined to develop hypertension are lacking. METHODS: We
      included 20 women with exPE and 8 parous controls. At both 1- and 14-year
      postpartum (pp), we performed cardiac ultrasound and determined circulating
      levels of the metabolic syndrome variables. Of 14-year pp, 7 (35%) former
      patients had developed chronic hypertension. We compared these 7 former patients
      with both the 13 former patients who remained normotensive and the 8 parous
      controls using the Mann-Whitney U test and Kruskal-Wallis analysis. RESULTS:
      Women with hypertensive exPE differed from their normotensive counterparts by a
      higher incidence of early-onset preeclampsia (PE) in their index pregnancy and a
      higher rate of recurrence in next pregnancies. At 1-year pp, they also had
      high/normal BP and higher fasting insulin levels. At 14 years pp, the relative
      left ventricular wall thickness was higher, and the E/A ratio was lower, in the
      hypertensive group relative to those remaining normotensive. CONCLUSION: Women
      with exPE are at increased risk of developing chronic hypertension, when (1) the
      PE in the index pregnancy had an early-onset and/or recurred in next pregnancies
      and (2) the 1-year pp. Blood pressure was high normal. We also noticed that at 14
      years pp, the hypertensive group showed signs of concentric left ventricular
      remodeling along with a decreased E/A ratio.

PMID- 24440999
TI  - From the editor.

PMID- 24441000
TI  - Person-environment relations.
AB  - The interaction that occurs between individuals and their environment is central
      to all work and rehabilitation practice. In the past, rehabilitation has focused
      more on facilitating personal adaptation and less on understanding the influence
      of the environment on behavior. Eight person-environment models, developed by
      other disciplines but of relevance to rehabilitation, are presented and
      discussed. The way in which each of these models views the person, the
      environment, the person-environment relationship, and adaptation is compared and
      contrasted to views inherent in rehabilitation practice. The literature suggests
      that rehabilitation is gradually moving from an interactive perspective of person
      environment fit toward a transaction view that more accurately acknowledges the
      complexity and the entwined nature of these issues. 

PMID- 24441001
TI  - Women in PovertyConsiderations for Occupational Therapy.
AB  - The majority of poor people in the United States are women. This article
      discusses the causes and occupational limitations of being a poor woman in
      affluent America. The inequality women face at work and the impact of the welfare
      institution are both central issues in the proliferation and feminization of
      poverty. Occupational therapists treating poor women must be aware of the
      implications poverty has on occupational choices. As they seek to enhance the
      lives of poor women, therapists must be prepared to assist them in specific
      struggles of oppression, budgeting, parenting, self-esteem, and work and in the
      use of the social welfare system. This paper offers information and questions to
      occupational therapists who work with women living in poverty. 

PMID- 24441002
TI  - The Atnericans With Disabilities Act Title IWhat Do We Know About Reasonable
      Accommodations For Individuals With Psychiatric Disabilities?
AB  - Title I is the employment provision of the Americans With Disabilities Act (ADA).
      Mental Illness is one category the ADA includes under its term mental impairment.
      This paper provides background on the ADA and discusses common functional
      limitations for individuals with psychiatric disabilities, as well as possible
      reasonable accommodations an employer may be required to provide under the law. 

PMID- 24441003
TI  - The just right challenge.
AB  - This paper is based on a keynote address "The Just Right Challenge" given on
      October 14, 1993, at Massachusetts Association for Occupational Therapy Annual
      Conference in Marlborough, MA. The occupational therapy profession is accountable
      to the society it serves. This paper outlines some key internal and external
      influences affecting the profession as it prepares for the next decade. Internal
      influences include the sphere of expertise, role clarification, and competencies.
      External influences include the use of service extenders, cross training, and
      practice parameters. 

PMID- 24441004
TI  - Industrial RehabilitationA Natural Environment for Occupational Therapy
      Practitioners.
AB  - The trend in developing return-to-work services and/or injury-prevention
      education programs has become a focus in marry hospital-based rehabilitation
      programs and physical therapy private practices during the past decade.
      Occupational therapy practitioners are well prepared for contributing to these
      programs. One of the three areas of occupational performance defined in the
      occupational therapy literature is "work". Facilitating maximum independence,
      preventing further disability, and promoting health are areas occupational
      therapy practitioners always consider, regardless of the injury or illness. This
      article discusses industrial rehabilitation programs and the role of occupational
      therapy practitioners participating in such programs. 

PMID- 24441005
TI  - Functional activities versus work hardening in the rehabilitation of the injured
      worker.
AB  - A correlational study was carried out to consider whether a program based on a
      work-hardening paradigm would result in objective improvements in return-to-work
      rates relative to a functional-activities approach. Subjects, 165 nurses, were
      obtained from the Alberta Workers' Compensation Board Rehabilitation Centre
      client files. The clients were described relative to their age, accident-to
      admission times, length of stay, and other relevant measures. A logistic
      regression was carried out to ascertain whether a work-hardening program versus a
      functional-activities program would be more effective in facilitating return-to
      work rates. The logistic regression was carried out controlling for other
      relevant predictor variables. The results indicated that clients who received a
      work-hardening program were statistically more likely to return to work. 

PMID- 24441006
TI  - The Vocational Training FacilityAn Interactive Learning Program to Return Persons
      With Physical Disabilities to Employment.
AB  - This paper describes the results of the program-development phase of the
      Vocational Training Facility (VTF) taking place at the Palo Alto Veterans Affairs
      Medical Center Rehabilitation Research and Development Center. The VTF staff has
      developed a self-paced, multimedia curriculum comprised of adapted training
      packages, interactive videos, and additional training and testing materials
      designed to teach entry-level desktop publishing and reasonable accommodation
      skills to individuals with spinal cord injuries. The curriculum is taught via the
      MacintoshTM computer to allow independent, "hands-off" access to training
      materials. Each student is given an integrated workstation that is equipped with
      the Desktop Vocational Assistant Robot (De VAR); a set of low-and high-technology
      assistive hardware, software, and devices; and ergonomic furniture and
      adaptations customized to fit individual learning and access needs. Each student
      completes a 12-week, full-time training program followed by a 3-month internship
      with a local corporate sponsor. This paper summarizes the evaluation results of
      the VTF program by the first nine students, with spinal cord injuries ranging
      paraplegia to high-level quadriplegia, who have completed the program. 

PMID- 24441007
TI  - The integration of computers and hand therapy.
AB  - Computer technology has enabled the DCH Outpatient Hand Therapy Clinic to
      formulate specialty evaluations and forms as well as perform a commercially
      developed comprehensive hand evaluation. Computers have the capability of
      creating attractive, diverse, and practical products in much less time and with
      more accuracy than when manually generated. We have learned that even the most
      inexperienced computer user can become proficient. Technology, creativity, and
      necessity have allowed us to expand beyond the EVAL(r) to word processing, form
      generation, and data-base management. 

PMID- 24441008
TI  - Learning-Disabled DriversWhat Do They Need to Succeed?
AB  - Driving skills are sometimes overlooked in the learning-disabled child's
      development until late adolescence or early adulthood. This late consideration of
      a complex skill may present an overwhelming challenge to a developmentally
      delayed individual. A case study of a successful learning-disabled driver
      suggests that childhood predriving skills, specialized training, and an
      integrated network of resources help to ensure the learning disabled driver's
      success. 

PMID- 24441009
TI  - An effective preemployment screening protocol.
AB  - Preemployment screening tests have been analyzed in the past for their validity
      and predictability. This study (for a specific work population) demonstrates
      correlation between a control group and the tested group of workers which
      effectively assesses the probability of injury. In the study, 17 variables were
      utilized to determine the classification of a prospective worker into a high risk
      or a low risk group with strong statistical significance. 

PMID- 24441010
TI  - Successful Return to WorkAre Ergonomic Modifications Worth the Cost?
AB  - Most of us hold opinions on contemporary issues in work practice, in all its
      broad dimensions. "Sounding Board" is a regular feature of this publication,
      designed to provide a forum for expressing such views, whether mainstream or
      controversial.The opinions expressed in this section may not necessarily
      represent the views of the editor, the publisher, or the editorial board but are
      intended to stimulate discussion or to provoke a response. Readers who wish to
      comment on the ideas put forth in "Sounding Board" should address their comments
      to the editor. 

PMID- 24441012
TI  - Keyword index 1994.

PMID- 24441013
TI  - Happy babies, chatty toddlers: infant positive affect facilitates early
      expressive, but not receptive language.
AB  - Eighty-three mother-infant dyads participated in this study. Positive affect (PA)
      broadly, along with fine-grained aspects of PA, was measured at 10 months of age.
      Language was measured at 14 months. Infant PA predicted expressive, but not
      receptive, language. The implications of these findings are discussed. 

PMID- 24441014
TI  - Total synthesis of sulfolipid-1.
AB  - Sulfolipid-1, a tetra-acylated sulfotrehalose from Mycobacterium tuberculosis,
      was isolated over 40 years ago. Being a main component of the mycomembrane of M.
      tuberculosis, its biosynthesis and function have been studied in depth, but the
      chemical synthesis of sulfolipid-1 has not been reported. The synthesis presented
      here is based on iterative catalytic asymmetric conjugate additions of
      methylmagnesium bromide for the preparation of the phthioceranic and
      hydroxyphthioceranic acid side chains, a double regioselective reductive ring
      opening and a fivefold deprotection in the final step. 

PMID- 24441015
TI  - The effect of electron localization on the electronic structure and migration
      barrier of oxygen vacancies in rutile.
AB  - By applying the on-site Coulomb interaction (Hubbard term U) to the Ti d orbital,
      the influence of electron localization on the electronic structure as well as the
      transport of oxygen vacancies (VO) in rutile was investigated. With U = 4.5 eV,
      the positions of defect states in the bandgap were correctly reproduced. The
      unbonded electrons generated by taking out one neutral oxygen atom are spin
      parallel and mainly localized on the Ti atoms near VO, giving rise to a magnetic
      moment of 2 MUB, in agreement with the experimental finding. With regard to the
      migration barrier of VO, surprisingly, we found that U = 4.5 eV only changed the
      value of the energy barrier by +/-0.15 eV, depending on the diffusion path. The
      most probable diffusion path (along [110]) is the same as that calculated by
      using the traditional GGA functional. To validate the GGA + U method itself, a
      hybrid functional with a smaller supercell was used, and the trend of the more
      probable diffusion path was not changed. In this regard, the traditional GGA
      functional might still be reliable in the study of intrinsic-defect
      transportation in rutile. Analyzing the atomic distortion and density of states
      of the transition states for different diffusion paths, we found that the
      anisotropy of the diffusion could be rationalized according to the various atomic
      relaxations and the different positions of the valence bands relative to the
      Fermi level of the transition states.

PMID- 24441017
TI  - The use of multivariate curve resolution methods to improve the analysis of
      muramic acid as bacterial marker using gas chromatography-mass spectrometry: an
      alternative method to gas chromatography-tandem mass spectrometry.
AB  - In analysis of muramic acid (MA) as bacterial marker, two dominant disturbing
      factors lead the researchers to use gas chromatography-tandem mass spectrometry
      (GC-MS/MS) technique instead of gas chromatography-mass spectrometry (GC-MS).
      These factors are the trace concentration of MA and fundamental disturbance of
      base line mass channels in GC-MS technique. This study aimed to utilize
      multivariate curve resolution (MCR) methods combined with GC-MS to improve the
      analysis of MA. First, the background and noise in GC-MS analysis were corrected
      and reduced using MCR methods. In addition, the MA overlapped peaks were resolved
      to its pure chromatographic and mass spectral profiles. Then the two-way response
      of each component was reconstructed by the outer product of the pure
      chromatographic and mass spectral profiles. The overall volume integration (OVI)
      method was used for quantitative determination. The MA peak area was decreased
      dramatically after the background correction and noise reduction. The findings
      severely ratify the appropriateness of using MCR techniques combined with GC-MS
      analysis as a simple, fast and inexpensive method for the analysis of MA in
      complex mixtures. The proposed method may be considered as an alternative method
      to GC-MS/MS for thorough analysis of the bacterial marker. 

PMID- 24441016
TI  - A potential wound healing-promoting peptide from frog skin.
AB  - Cutaneous wound healing is a dynamic, complex, and well-organized process that
      requires the orchestration of many different cell types and cellular processes.
      Transforming growth factor beta1 is an important factor that plays a key role
      during wound healing. Amphibian skin has been proven to possess excellent wound
      healing ability, whilst no bioactive substrate related to it has ever been
      identified. Here, a potential wound healing-promoting peptide (AH90,
      ATAWDFGPHGLLPIRPIRIRPLCG) was identified from the frog skin of Odorrana grahami.
      It showed potential wound healing-promoting activity in a murine model with full
      thickness dermal wound. AH90 promoted release of transforming growth factor beta1
      through activation of nuclear factor-kappaB and c-Jun NH2-terminal kinase mitogen
      activated protein kinases signaling pathways, while inhibitors of nuclear factor
      kappaB and c-Jun NH2-terminal kinase inhibited the process. In addition, the
      effects of AH90 on Smads family proteins, key regulators in transforming growth
      factor beta1 signaling pathways, could also be inhibited by transforming growth
      factor beta1 antibody. Altogether, this indicated that AH90 promoted wound
      healing by inducing the release of transforming growth factor beta1. This current
      study may facilitate the understanding of effective factors involved in the wound
      repair of amphibians and the underlying mechanisms as well. Considering its
      favorable traits as a small peptide that greatly promoting generation of
      endogenous wound healing agents (transforming growth factor beta1) without
      mitogenic effects, AH90 might be an excellent template for the future development
      of novel wound-healing agents. 

PMID- 24441018
TI  - Simultaneous determination of caffeic acid derivatives by UPLC-MS/MS in rat
      plasma and its application in pharmacokinetic study after oral administration of
      Flos Lonicerae-Fructus Forsythiae herb combination.
AB  - The current study aims to investigate the pharmacokinetic study of eight caffeic
      acid derivatives (forsythoside A, isoforsythoside, forsythoside B, neochlorogenic
      acid, chlorogenic acid, cryptochlorogenic acid, 3,5-dicaffeoylquinic acid and 3,4
      dicaffeoylquinic acid) following oral administration of Flos Lonicerae-Fructus
      Forsythiae herb combination in rats. A rapid and sensitive ultra performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed
      to determine the eight caffeic acid derivatives simultaneously in rat plasma.
      After mixing with the internal standard (IS) tinidazole, plasma samples were
      pretreated by liquid-liquid extraction with n-butyl alcohol/ethyl acetate (7:3,
      v/v). The separation was performed on an Acquity UPLC HSS T3 C18 column
      (100mm*2.1mm, 1.8MUm) at a flow rate of 0.4mLmin(-1), and acetonitrile/methanol
      (4:1, v/v)-0.4% formic acid was used as mobile phase. The detection was performed
      on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring
      (MRM) via electrospray ionization (ESI) source with positive and negative
      ionization modes. All calibration curves had good linearity (r>0.991) over the
      concentration ranges of 1.097-2246ngmL(-1) for neochlorogenic acid, 6.535
      6692ngmL(-1) for chlorogenic acid, 2.103-2153ngmL(-1) for cryptochlorogenic acid,
      0.5058-129.5ngmL(-1) for 3,5-dicaffeoylquinic acid, 0.3205-82.05ngmL(-1) for 3,4
      dicaffeoylquinic acid, 1.002-512.8ngmL(-1) for isoforsythoside, 0.4795-982.1ngmL(
      1) for forsythoside A and 0.7587-776.9ngmL(-1) for forsythoside B, respectively.
      The intra- and inter-batch precisions were all within 15% and the accuracy
      (relative error, RE%) all ranged from 85.68% to 114.7%. It was shown from
      pharmacokinetic parameters that the rank order of AUC0-t, Cmax and T1/2k for
      phenolic acids was chlorogenic acid>neochlorogenic acid>=cryptochlorogenic
      acid>3,4-dicaffeoylquinic acid>=3,5-dicaffeoylquinic acid (most of them had
      significant differences), which corresponded to their administration dosages to
      rats, but that of MRT0-t and T1/2z were opposite. Besides, the AUC0-t, Cmax, MRT
      and T1/2z except T1/2k of isoforsythoside and forsythoside B had no significant
      difference, compared to that of forsythoside A though their administration
      dosages were significantly lower than that of forsythoside A. All results showed
      that the method was applied to the pharmacokinetic study of the eight caffeic
      acid derivatives in rat plasma successfully after oral administration of Flos
      Lonicerae-Fructus Forsythiae herb combination, and there were significant
      differences of caffeic acid derivatives even isomers in the pharmacokinetic
      parameters. 

PMID- 24441020
TI  - Potential of multispectral imaging technology for rapid and non-destructive
      determination of the microbiological quality of beef filets during aerobic
      storage.
AB  - The performance of a multispectral imaging system has been evaluated in
      monitoring aerobically packaged beef filet spoilage at different storage
      temperatures (0, 4, 8, 12, and 16 degrees C). Spectral data in the visible and
      short wave near infrared area (405-970nm) were collected from the surface of meat
      samples and correlated with microbiological data (log counts), for total viable
      counts (TVCs), Pseudomonas spp., and Brochothrix thermosphacta. Qualitative
      analysis (PLS-DA) was employed for the discrimination of meat samples in three
      microbiological quality classes based on the values of total viable counts,
      namely Class 1 (TVC<5.5log10CFU/g), Class 2 (5.5log10CFU/g<TVC<7.0log10CFU/g),
      and Class 3 (TVC>7.0log10CFU/g). Furthermore, PLS regression models were
      developed to provide quantitative estimations of microbial counts during meat
      storage. In both cases model validation was implemented with independent
      experiments at intermediate storage temperatures (2 and 10 degrees C) using
      different batches of meat. Results demonstrated good performance in classifying
      meat samples with overall correct classification rate for the three quality
      classes ranging from 91.8% to 80.0% for model calibration and validation,
      respectively. For quantitative estimation, the calculated regression coefficients
      between observed and estimated counts ranged within 0.90-0.93 and 0.78-0.86 for
      model development and validation, respectively, depending on the microorganism.
      Moreover, the calculated average deviation between observations and estimations
      was 11.6%, 13.6%, and 16.7% for Pseudomonas spp., B. thermosphacta, and TVC,
      respectively. The results indicated that multispectral vision technology has
      significant potential as a rapid and non-destructive technique in assessing the
      microbiological quality of beef fillets. 

PMID- 24441019
TI  - A systems approach to designing next generation vaccines: combining alpha
      galactose modified antigens with nanoparticle platforms.
AB  - Innovative vaccine platforms are needed to develop effective countermeasures
      against emerging and re-emerging diseases. These platforms should direct antigen
      internalization by antigen presenting cells and promote immunogenic responses.
      This work describes an innovative systems approach combining two novel platforms,
      alphaGalactose (alphaGal)-modification of antigens and amphiphilic polyanhydride
      nanoparticles as vaccine delivery vehicles, to rationally design vaccine
      formulations. Regimens comprising soluble alphaGal-modified antigen and
      nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity
      antibody response with broader epitope recognition of antigenic peptides than
      other regimen. Proliferation of antigen-specific CD4(+) T cells was also enhanced
      compared to a traditional adjuvant. Combining the technology platforms and
      augmenting immune response studies with peptide arrays and informatics analysis
      provides a new paradigm for rational, systems-based design of next generation
      vaccine platforms against emerging and re-emerging pathogens. 

PMID- 24441021
TI  - Inactivation of naturally occurring microbiota in cucumber juice by pressure
      treatment.
AB  - The inactivation effects of high hydrostatic pressure (HHP) (350MPa/10min,
      400MPa/4min and 500MPa/2min) with homogenization (20MPa/2min), nisin (100IU/mL)
      and decompression time (<3s and 7-8s) on naturally occurring microbiota in
      cucumber juice were investigated. Initial concentration of yeasts and molds (Y&M)
      was 5.6*10(3)-2.4*10(4)CFU/mL, and total plate count (TPC) was 1.0*10(5)
      3.5*10(5)CFU/mL. Y&M were inactivated below the detection level (<=10CFU/mL) in
      all cases. The reduction of TPC in non-homogenized cucumber juice (NHCJ) was 2.5
      3.0 log cycles, which was significantly higher than 1.0 log cycle in homogenized
      cucumber juice. The combination of nisin with HHP had a synergistic effect on the
      inactivation of TPC. The reduction of TPC in NHCJ with a decompression time of
      <3s was approximately 4.5 log cycles, which was significantly higher than a
      decompression time of 7-8s. Five non-linear models including the biphasic,
      Weibull, modified Gompertz, log-logistic and Baranyi models were fitted to TPC
      inactivation curves for the NHCJ at 300, 350 and 400MPa for 2-15min and 500MPa
      for 2-8min at a decompression time of <3s. The biphasic model provided the best
      fit for the data. 

PMID- 24441022
TI  - Novel fluorescent probes for highly selective two-photon imaging of mitochondria
      in living cells.
AB  - The synthesis and characterization of a pair of novel pyridine cation derivatives
      possessing two-photon excitation fluorescence (TPEF) properties and selectively
      staining mitochondria in living SiHa cells within 30 min, CAI and CAEI, were
      reported. And the green-emitting CAI displayed a much larger two-photon
      excitation fluorescence action absorption cross-section (delta * Phi) of 328 g at
      860 nm in comparison with commercial MitoTracker Green (MTG) with maximum delta *
      Phi value of 2.18 g at 850 nm. As is known to all, delta * Phi is a crucial
      parameter to obtain a high-quality microscopic photo in living cells in two
      photon microscopy (TPM). Moreover, the fact that the co-localization coefficient
      between CAI and conventional MitoTracker Red (MTR) was 0.95 in SiHa cells
      demonstrated specific staining performance of CAI to mitochondria. As biosensors,
      both CAI and CAEI possessed a number of beneficial properties such as large delta
      * Phi and Stokes shifts, good membrane permeability, long retention time, high
      photostability and excellent counterstain compatibility with different biosensors
      for instance Hoechst 33342 and D 307, which ranked them as one of the best TPEF
      mitochondrial probes. Furthermore, related mechanism research suggested that
      their localization properties were dependent on the mitochondrial membrane
      potential in living cells. And their remarkable properties can extend the
      investigation on mitochondria in a biological context.

PMID- 24441023
TI  - Nanostructured enzymatic biosensor based on fullerene and gold nanoparticles:
      preparation, characterization and analytical applications.
AB  - In this work a novel electrochemical biosensing platform based on the coupling of
      two different nanostructured materials (gold nanoparticles and fullerenols)
      displaying interesting electrochemical features, has been developed and
      characterized. Gold nanoparticles (AuNPs) exhibit attractive electrocatalytic
      behavior stimulating in the last years, several sensing applications; on the
      other hand, fullerene and its derivatives are a very promising family of
      electroactive compounds although they have not yet been fully employed in
      biosensing. The methodology proposed in this work was finalized to the setup of a
      laccase biosensor based on a multilayer material consisting in AuNPs, fullerenols
      and Trametes versicolor Laccase (TvL) assembled layer by layer onto a gold (Au)
      electrode surface. The influence of different modification step procedures on the
      electroanalytical performance of biosensors has been evaluated. Cyclic
      voltammetry, chronoamperometry, surface plasmon resonance (SPR) and scanning
      tunneling microscopy (STM) were used to characterize the modification of surface
      and to investigate the bioelectrocatalytic biosensor response. This biosensor
      showed fast amperometric response to gallic acid, which is usually considered a
      standard for polyphenols analysis of wines, with a linear range 0.03-0.30 mmol L(
      1) (r(2)=0.9998), with a LOD of 0.006 mmol L(-1) or expressed as polyphenol index
      5.0-50 mg L(-1) and LOD 1.1 mg L(-1). A tentative application of the developed
      nanostructured enzyme-based biosensor was performed evaluating the detection of
      polyphenols either in buffer solution or in real wine samples.

PMID- 24441024
TI  - Continuous monitoring of bisulfide variation in microdialysis effluents by on
      line droplet-based microfluidic fluorescent sensor.
AB  - We demonstrate a novel fluorescent sensor for real-time and continuous monitoring
      of the variation of bisulfide in microdialysis effluents by using a nanoparticle
      glutathione-fluorescein isothiocyanate (AuNP-GSH-FITC) probe coupled with on-line
      droplet-based microfluidic chip. The AuNP-GSH-FITC fluorescent probe was firstly
      developed and used for bisulfide detection in bulk solution by quantitative real
      time PCR, which achieved a linear working range from 0.1 MUM to 5.0 MUM and a
      limit of detection of ~50 nM. The response time was less than 2 min. With the aid
      of co-immobilized thiol-polyethylene glycol, the probe exhibited excellent
      stability and reproducibility in high salinity solutions, including artificial
      cerebrospinal fluids (aCSF). By adding 0.1% glyoxal to the probe solution, the
      assay allowed quantification of bisulfide in the presence of cysteine at the
      micro-molarity level. Using the AuNP-GSH-FITC probe, a droplet-based microfluidic
      fluorescent sensor was further constructed for online monitoring of bisulfide
      variation in the effluent of microdialysis. By using fluorescence microscope
      charge-coupled device camera as the detector, the integrated
      microdialysis/microfluidic chip device achieved a detection limit of 2.0 MUM and
      a linear response from 5.0 MUM to 50 MUM for bisulfide in the tested sample. The
      method was successfully applied for the on-line measurement of bisulfide
      variation in aCSF and serum samples. It will be a very useful tool for tracking
      the variation of bisulfide or hydrogen sulfide in extracellular fluids.

PMID- 24441025
TI  - The protective effects of the combination of sodium ferulate and oxymatrine on
      ethanol-induced liver damage in mice.
AB  - The aim of this study was to investigate the effects of the combination of SF and
      OMT on ethanol-induced liver damage in mice. The animal liver wet/dry weight
      (W/D) ratio and liver tissue histopathology, alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA),
      superoxidase dismutase (SOD), C-reactive protein (CRP), interleukin-6 (IL-6), and
      nuclear factor kappaB (NF-kappaB) levels were measured. The data indicated that
      the levels of ALT, AST, TG, CRP, IL-6, NF-kappaB and MDA significantly decreased
      and that SOD activity improved after treatment with the combination of SF and
      OMT; the same effects were not observed with the same dose of SF or OMT when used
      alone. These results indicated that the combination of SF and OMT had a
      protective effect on ethanol-induced liver damage in mice and that antioxidation
      and anti-inflammatory effects might be involved in this protective mechanism. 

PMID- 24441026
TI  - Effect of antiretroviral drugs on the DNA damage in mice.
AB  - In order to investigate the effects of two non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) on the DNA damage in vivo, nevirapine (NVP; 3.3 mg/kg),
      efavirenz (EFV; 10 mg/kg) or saline were administered orally. Acute effects were
      analyzed 24 h after the administration of a single NNRTI dose, and subchronic
      effects 24 h after the last dose. Peripheral blood, brain, heart and liver
      samples were subjected to genotoxicity analyses and polychromatic erythrocytes
      from the bone marrow to micronucleus test. The micronucleus test did not reveal
      any significant differences between animals from the acute or subchronic groups.
      Comet assay showed that acute and subchronic NNRTI treatment did not cause any
      significant DNA damage in heart, liver or peripheral blood cells. However,
      increased damage indexes and frequencies were observed in the brain of mice,
      subchronically treated with EFV. This result suggests for the first time that
      this drug might induce genotoxicity in the brain.

PMID- 24441029
TI  - Spin-crossover phenomena of the mononuclear Mn(III) complex tuned by metal
      dithiolene counteranions.
AB  - Three ion-pair complexes based on spin-crossover [Mn(5-Br-sal-N-1,5,8,12)]ClO4
      with TBA2[Ni(mnt)2], TBA2[Pt(mnt)2] (mnt = maleonitriledithiolate) and
      TBA[Ni(dmit)2] respectively (dmit = 2-thioxo-1,3-dithiole-4,5-dithiolato) have
      been synthesized and structurally characterized. Complexes [Mn(5-Br-sal-N
      1,5,8,12)]2[Ni(mnt)2] and [Mn(5-Br-sal-N-1,5,8,12)]2[Pt(mnt)2] are isomorphic and
      show the axial compression of the octahedral coordination environment of Mn(III)
      ions. With the temperature increasing the equatorial metal-ligand bond lengths
      show significant elongation, but the axial bond lengths remain unchanged. Complex
      [Mn(5-Br-sal-N-1,5,8,12)][Ni(dmit)2].CH3CN contains pi-pi, p-pi and H-bonds weak
      interactions. Magnetic investigation shows the spin-crossover phenomena for and ,
      and T1/2 has been increased by 230 K comparing with the reactant complex.
      However, no spin-crossover was observed in complex , and theoretical calculations
      show that there are weak antiferromagnetic couplings mediated through pi-pi
      interactions. 

PMID- 24441030
TI  - A systematic review of interventions for anxiety, depression, and PTSD in adult
      offenders.
AB  - There is a high prevalence of anxiety and depression in offender populations but
      with no recent systematic review of interventions to identify what is effective.
      This systematic review was undertaken to identify randomised controlled trials of
      pharmacological and non-pharmacological interventions in adult offenders in
      prison or community settings. A search of five databases identified 14 studies
      meeting inclusion criteria, which considered the impact of psychological
      interventions, pharmacological agents, or exercise on levels of depression and
      anxiety. A narrative synthesis was undertaken and Hedges g effect sizes
      calculated to allow comparison between studies. Effect sizes for depression
      interventions ranged from 0.17 to 1.41, for anxiety 0.61 to 0.71 and for
      posttraumatic stress disorder 0 to 1.41. Cognitive behavioural therapy
      interventions for the reduction of depression and anxiety in adult offenders
      appear effective in the short term, though a large-scale trial of sufficient
      duration is needed to confirm this finding. 

PMID- 24441031
TI  - Revenge: An Analysis of Its Psychological Underpinnings.
AB  - An overview of the literature and theories concerning revenge is presented in
      this study. The aim is to clarify the boundaries between a healthy and
      pathological way of dealing with revenge to improve diagnostics, with regard to
      both theory and clinical practice. Revenge is an intrapersonal phenomenon and the
      extent to which people need revenge has a certain degree of stability. A healthy
      way of dealing with revenge may restore the psychological balance that has
      previously been disturbed. However, the desire for revenge can be long-lasting
      and dysfunctional due to, among other things, early problems in development and
      specific personality traits. Consequently, a pathological way of dealing with
      revenge can be part of a disorder and can lead to destructive acts such as
      homicide and even mass murder. Some clinical examples are presented and points of
      attention regarding diagnostics and treatment are discussed. 

PMID- 24441033
TI  - An amino acid substitution-selection model adjusts residue fitness to improve
      phylogenetic estimation.
AB  - Standard protein phylogenetic models use fixed rate matrices of amino acid
      interchange derived from analyses of large databases. Differences between the
      stationary amino acid frequencies of these rate matrices from those of a data set
      of interest are typically adjusted for by matrix multiplication that converts the
      empirical rate matrix to an exchangeability matrix which is then postmultiplied
      by the amino acid frequencies in the alignment. The result is a time-reversible
      rate matrix with stationary amino acid frequencies equal to the data set
      frequencies. On the basis of population genetics principles, we develop an amino
      acid substitution-selection model that parameterizes the fitness of an amino acid
      as the logarithm of the ratio of the frequency of the amino acid to the frequency
      of the same amino acid under no selection. The model gives rise to a different
      sequence of matrix multiplications to convert an empirical rate matrix to one
      that has stationary amino acid frequencies equal to the data set frequencies. We
      incorporated the substitution-selection model with an improved amino acid class
      frequency mixture (cF) model to partially take into account site-specific amino
      acid frequencies in the phylogenetic models. We show that 1) the selection models
      fit data significantly better than corresponding models without selection for
      most of the 21 test data sets; 2) both cF and cF selection models favored the
      phylogenetic trees that were inferred under current sophisticated models and
      methods for three difficult phylogenetic problems (the positions of microsporidia
      and breviates in eukaryote phylogeny and the position of the root of the
      angiosperm tree); and 3) for data simulated under site-specific residue
      frequencies, the cF selection models estimated trees closer to the generating
      trees than a standard G model or cF without selection. We also explored several
      ways of estimating amino acid frequencies under neutral evolution that are
      required for these selection models. By better modeling the amino acid
      substitution process, the cF selection models will be valuable for phylogenetic
      inference and evolutionary studies. 

PMID- 24441032
TI  - Effectiveness of Choice Theory Connections: a cross-sectional and comparative
      analysis of California female inmates.
AB  - In the past 30 years, the rates of incarceration and recidivism for women in the
      United States have increased dramatically. Choice Theory(r) Connections (CTC) is
      a gender-tailored pre-release intervention program based on Choice Theory(r)
      (Glasser, 1999), and designed to achieve meaningful and sustainable cognitive and
      behavioral change. This evaluation examines CTC among 96 female participants in a
      California state prison enrolled in an introductory (n = 58) or advanced (n = 38)
      course. CTC significantly improved perceived stress, mindfulness, emotion
      regulation, impulsivity, and well-being on completion; effects were stronger for
      the introductory cohort, but significant effects also emerged for the advanced
      cohort. In addition, participants in the advanced cohort reported better scores
      at baseline, demonstrating the effects of prolonged engagement with the
      intervention. Results suggest that CTC can improve incarcerated women's well
      being pre-release, a strong predictor of recidivism post-release. Further study
      and wider use of CTC are encouraged. 

PMID- 24441034
TI  - Host resistance selects for traits unrelated to resistance-breaking that affect
      fitness in a plant virus.
AB  - The acquisition by parasites of the capacity to infect resistant host genotypes,
      that is, resistance-breaking, is predicted to be hindered by across-host fitness
      trade-offs. All analyses of costs of resistance-breaking in plant viruses have
      focused on within-host multiplication without considering other fitness
      components, which may limit understanding of virus evolution. We have reported
      that host range expansion of tobamoviruses on L-gene resistant pepper genotypes
      was associated with severe within-host multiplication penalties. Here, we analyze
      whether resistance-breaking costs might affect virus survival in the environment
      by comparing tobamovirus pathotypes differing in infectivity on L-gene resistance
      alleles. We predicted particle stability from structural models, analyzed
      particle stability in vitro, and quantified virus accumulation in different plant
      organs and virus survival in the soil. Survival in the soil differed among
      tobamovirus pathotypes and depended on differential stability of virus particles.
      Structure model analyses showed that amino acid changes in the virus coat protein
      (CP) responsible for resistance-breaking affected the strength of the axial
      interactions among CP subunits in the rod-shaped particle, thus determining its
      stability and survival. Pathotypes ranked differently for particle
      stability/survival and for within-host accumulation. Resistance-breaking costs in
      survival add to, or subtract from, costs in multiplication according to
      pathotype. Hence, differential pathotype survival should be considered along with
      differential multiplication to understand the evolution of the virus populations.
      Results also show that plant resistance, in addition to selecting for resistance
      breaking and for decreased multiplication, also selects for changes in survival,
      a trait unrelated to the host-pathogen interaction that may condition host range
      expansion. 

PMID- 24441035
TI  - A cluster of olfactory receptor genes linked to frugivory in bats.
AB  - Diversity of the mammalian olfactory receptor (OR) repertoire has been globally
      reshaped by niche specialization. However, little is known about the variability
      of the OR repertoire at a shallower evolutionary timeframe. The vast bat
      radiation exhibits an extraordinary variety of trophic and sensory
      specializations. Unlike other mammals, bats possess a unique and diverse OR gene
      repertoire. We elucidated whether the evolution of the OR gene repertoire can be
      linked to ecological niche specializations, such as sensory modalities and diet.
      The OR gene repertoires of 27 bat species spanning the chiropteran radiation were
      amplified and sequenced. For each species, intact and nonfunctional genes were
      assessed, and the OR gene abundances in each gene family were analyzed and
      compared. We identified a unique OR pattern linked to the frugivorous diet of New
      World fruit-eating bats and a similar convergent pattern in the Old World fruit
      eating bats. Our results show a strong association between niche specialization
      and OR repertoire diversity even at a shallow evolutionary timeframe. 

PMID- 24441036
TI  - Emergence and evolutionary analysis of the human DDR network: implications in
      comparative genomics and downstream analyses.
AB  - The DNA damage response (DDR) is a crucial signaling network that preserves the
      integrity of the genome. This network is an ensemble of distinct but often
      overlapping subnetworks, where different components fulfill distinct functions in
      precise spatial and temporal scenarios. To understand how these elements have
      been assembled together in humans, we performed comparative genomic analyses in
      47 selected species to trace back their emergence using systematic phylogenetic
      analyses and estimated gene ages. The emergence of the contribution of
      posttranslational modifications to the complex regulation of DDR was also
      investigated. This is the first time a systematic analysis has focused on the
      evolution of DDR subnetworks as a whole. Our results indicate that a DDR core,
      mostly constructed around metabolic activities, appeared soon after the emergence
      of eukaryotes, and that additional regulatory capacities appeared later through
      complex evolutionary process. Potential key posttranslational modifications were
      also in place then, with interacting pairs preferentially appearing at the same
      evolutionary time, although modifications often led to the subsequent acquisition
      of new targets afterwards. We also found extensive gene loss in essential modules
      of the regulatory network in fungi, plants, and arthropods, important for their
      validation as model organisms for DDR studies. 

PMID- 24441037
TI  - Breath carbon stable isotope ratios identify changes in energy balance and
      substrate utilization in humans.
AB  - Rapid detection of shifts in substrate utilization and energy balance would
      provide a compelling biofeedback tool for individuals attempting weight loss. As
      a proof of concept, we tested whether the natural abundance of exhaled carbon
      stable isotope ratios (breath delta(13)C) reflects shifts between negative and
      positive energy balance. Volunteers (n=5) consumed a 40% energy-restricted diet
      for 6 days followed by 50% excess on day 7. Breath was sampled immediately before
      and 1 h and 2 h after breakfast, lunch and dinner. Exhaled breath delta(13)C
      values were measured by cavity ring-down spectroscopy. Using repeated measures
      analysis of variance (ANOVA) followed by Dunnett's contrasts, pre-breakfast
      breath values on days 2-6 were compared with day 1, and postprandial day 7 time
      points were compared with pre-breakfast day 7. Energy restriction diminished pre
      breakfast breath delta(13)C by day 3 (P<0.05). On day 7, increased energy intake
      was first detected immediately before dinner (-23.8+/-0.6 vs -21.9+/-0.70/00,
      P=0.002 (means+/-s.d.)), and breath delta(13)C remained elevated at least 2 h
      post dinner. In conclusion, when shifting between negative and positive energy
      balance, breath delta(13)C showed anticipated isotopic changes. Although
      additional research is needed to determine specificity and repeatability, this
      method may provide a biomarker for marked increases in caloric intake. 

PMID- 24441038
TI  - Chickens from lines selected for high and low body weight show differences in
      fatty acid oxidation efficiency and metabolic flexibility in skeletal muscle and
      white adipose tissue.
AB  - OBJECTIVE: The Virginia lines of chickens have resulted from more than 55
      generations of artificial selection for low (LWS) or high (HWS) juvenile body
      weight. We hypothesized that the relative hyperphagia and greater body weight in
      juvenile HWS chickens are associated with altered fatty acid oxidation efficiency
      and metabolic flexibility in tissues associated with energy sensing and storage,
      and relative cellular hypertrophy in white adipose tissue. METHODS: Hypothalamus,
      liver, pectoralis major, gastrocnemius, abdominal fat, clavicular fat and
      subcutaneous fat were collected from the juvenile (56-65 days old) LWS and HWS
      chickens for metabolic, gene expression and histological assays. RESULTS: The HWS
      chickens had reduced fatty acid oxidation efficiency in abdominal fat (P<0.0001)
      and reduced rates of oxidation in abdominal fat and gastrocnemius (P<0.0001) as
      compared with the LWS. There was reduced citrate synthase activity in white
      adipose tissue (P<0.0001) and greater metabolic inflexibility in skeletal muscle
      (P=0.006) of the HWS compared with the LWS. Greater pyruvate dehydrogenase kinase
      4 (PDK4) and forkhead box O1A (FoxO1) mRNA were found in skeletal muscle and
      white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma) in all adipose tissue depots
      was greater (P<0.05) in LWS than in HWS chickens. The HWS chickens had larger
      (P<0.0001) and fewer (P<0.0001) adipocytes per unit area than the LWS.
      CONCLUSION: Compared with the LWS, the HWS chickens have impaired metabolic
      flexibility and fatty acid oxidation efficiency due to greater pyruvate
      dehydrogenase activity to accommodate the influx of acetyl-CoA from fatty acid
      oxidation in skeletal muscle and adipose tissue. These metabolic adaptations can
      be linked to differences in gene expression regulation, adipocyte cellularity and
      body composition between the lines, which may provide valuable insight into
      metabolic disorders in other species.

PMID- 24441039
TI  - Asporin activates coordinated invasion of scirrhous gastric cancer and cancer
      associated fibroblasts.
AB  - Scirrhous gastric cancer, which has the worst prognosis among the various types
      of gastric cancer, is highly invasive and associated with abundant stromal
      fibroblasts. Although cancer-associated fibroblasts (CAFs) have been proposed to
      generate a tumor-supportive extracellular matrix that promotes the expansion of
      this type of cancer, the molecular mechanisms by which CAFs assist cancer cells
      are not yet fully understood. Here, we show for the first time that Asporin, a
      small leucine-rich proteoglycan (SLRP), is predominantly expressed in CAFs, and
      has essential roles in promoting co-invasion of CAFs and cancer cells. CAFs of
      scirrhous gastric cancer possess high potential for invasion, and invasion by
      CAFs frequently proceeded invasion by cancer cells, both in vitro and in vivo.
      Expression of Asporin was induced in fibroblasts by exposure to gastric cancer
      cells. Asporin secreted from CAFs activates Rac1 via an interaction with CD44 and
      promotes invasion by CAFs themselves. Moreover, Asporin promoted invasion by
      neighboring cancer cells, via paracrine effects mediated by activation of the
      CD44-Rac1 pathway. These results suggest that Asporin is a unique SLRP that
      promotes progression of scirrhous gastric cancer and is required for coordinated
      invasion by CAFs and cancer cells. Therefore, Asporin may represent a new
      therapeutic target molecule for the development of drugs aimed at manipulating
      the cancer microenvironment. 

PMID- 24441040
TI  - Alternative splicing in cancer: implications for biology and therapy.
AB  - Alternative splicing has critical roles in normal development and can promote
      growth and survival in cancer. Aberrant splicing, the production of noncanonical
      and cancer-specific mRNA transcripts, can lead to loss-of-function in tumor
      suppressors or activation of oncogenes and cancer pathways. Emerging data suggest
      that aberrant splicing products and loss of canonically spliced variants
      correlate with stage and progression in malignancy. Here, we review the splicing
      landscape of TP53, BARD1 and AR to illuminate roles for alternative splicing in
      cancer. We also examine the intersection between alternative splicing pathways
      and novel therapeutic approaches. 

PMID- 24441041
TI  - The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor alpha and
      modulates estrogen-stimulated breast cancer cell proliferation.
AB  - Estrogen receptor alpha (ERalpha) is initially expressed in the majority of
      breast cancers and promotes estrogen-dependent cancer progression by regulating
      the transcription of genes linked to cell proliferation. ERalpha status is of
      clinical importance, as ERalpha-positive breast cancers can be successfully
      treated by adjuvant therapy with antiestrogens or aromatase inhibitors.
      Complications arise from the frequent development of drug resistance that might
      be caused by multiple alterations, including components of ERalpha signaling,
      during tumor progression and metastasis. Therefore, insights into the molecular
      mechanisms that control ERalpha expression and stability are of utmost importance
      to improve breast cancer diagnostics and therapeutics. Here we report that the
      atypical E3 ubiquitin ligase RNF31 stabilizes ERalpha and facilitates ERalpha
      stimulated proliferation in breast cancer cell lines. We show that depletion of
      RNF31 decreases the number of cells in the S phase and reduces the levels of
      ERalpha and its downstream target genes, including cyclin D1 and c-myc. Analysis
      of data from clinical samples confirms correlation between RNF31 expression and
      the expression of ERalpha target genes. Immunoprecipitation indicates that RNF31
      associates with ERalpha and increases its stability and mono-ubiquitination,
      dependent on the ubiquitin ligase activity of RNF31. Our data suggest that
      association of RNF31 and ERalpha occurs mainly in the cytosol, consistent with
      the lack of RNF31 recruitment to ERalpha-occupied promoters. In conclusion, our
      study establishes a non-genomic mechanism by which RNF31 via stabilizing ERalpha
      levels controls the transcription of estrogen-dependent genes linked to breast
      cancer cell proliferation. 

PMID- 24441043
TI  - The role of sLZIP in cyclin D3-mediated negative regulation of androgen receptor
      transactivation and its involvement in prostate cancer.
AB  - Androgen and the androgen receptor (AR) have important roles in prostate cancer
      (PCa) development, and androgen ablation has been the main therapeutic option for
      the treatment of PCa. However, the transition mechanism from androgen-dependent
      to -independent PCa after androgen depletion remains unclear. We investigated the
      distinct roles of small leucine zipper protein (sLZIP) in proliferation of
      androgen-dependent and -independent PCa cells. Cyclin D3 is known to interact
      with AR and attenuates the ligand-dependent function of AR in PCa cells. sLZIP
      regulates the transcription of cyclin D3 by binding directly to the AP-1 region
      in the cyclin D3 promoter. sLZIP represses AR transcriptional activity by
      interaction with AR that is phosphorylated by cyclin D3/cyclin-dependent
      kinase11(p58), leading to the suppression of androgen-dependent proliferation of
      PCa cells. The expression level of sLZIP is elevated in androgen-independent PCa
      cells and advanced human prostate tumors. Knockdown of endogenous sLZIP
      suppresses proliferation of androgen-independent PCa cells. LNCaP cells
      transformed to androgen-independent PCa cells exhibit increased expressions of
      sLZIP and cyclin D3. Tumor formation is inhibited in nude mouse xenografts from
      two androgen-independent PCa cells that are stably transfected with sh-sLZIP. Our
      findings indicate that sLZIP negatively regulates AR transactivation in androgen
      dependent PCa cells and functions as a positive regulator in tumor progression of
      androgen-independent PCa. sLZIP contributes to the malignant phenotype of PCa and
      constitutes a novel therapeutic target for human PCa. 

PMID- 24441042
TI  - Systems level-based RNAi screening by high content analysis identifies UBR5 as a
      regulator of estrogen receptor-alpha protein levels and activity.
AB  - Estrogen receptor-alpha (ERalpha) is a central transcription factor that
      regulates mammary gland physiology and a key driver in breast cancer. In the
      present study, we aimed to identify novel modulators of ERalpha-mediated
      transcriptional regulation via a custom-built siRNA library screen. This screen
      was directed against a variety of coregulators, transcription modifiers,
      signaling molecules and DNA damage response proteins. By utilizing a microscopy
      based, multi-end point, estrogen responsive biosensor cell line platform, the
      primary screen identified a wide range of factors that altered ERalpha protein
      levels, chromatin remodeling and mRNA output. We then focused on UBR5, a
      ubiquitin ligase and known oncogene that modulates ERalpha protein levels and
      transcriptional output. Finally, we demonstrated that UBR5 also affects
      endogenous ERalpha target genes and E2-mediated cell proliferation in breast
      cancer cells. In conclusion, our multi-end point RNAi screen identified novel
      modulators of ERalpha levels and activity, and provided a robust systems level
      view of factors involved in mechanisms of nuclear receptor action and
      pathophysiology. Utilizing a high throughput RNAi screening approach we
      identified UBR5, a protein commonly amplified in breast cancer, as a novel
      regulator of ERalpha protein levels and transcriptional activity. 

PMID- 24441044
TI  - SUPT6H controls estrogen receptor activity and cellular differentiation by
      multiple epigenomic mechanisms.
AB  - The estrogen receptor alpha (ERalpha) is the central transcriptional regulator of
      ductal mammary epithelial lineage specification and is an important prognostic
      marker in human breast cancer. Although antiestrogen therapies are initially
      highly effective at treating ERalpha-positive tumors, a large number of tumors
      progress to a refractory, more poorly differentiated phenotype accompanied by
      reduced survival. A better understanding of the molecular mechanisms involved in
      the progression from estrogen-dependent to hormone-resistant breast cancer may
      uncover new targets for treatment and the discovery of new predictive markers.
      Recent studies have uncovered an important role for transcriptional elongation
      and chromatin modifications in controlling ERalpha activity and estrogen
      responsiveness. The human Suppressor of Ty Homologue-6 (SUPT6H) is a histone
      chaperone that links transcriptional elongation to changes in chromatin
      structure. We show that SUPT6H is required for estrogen-regulated transcription
      and the maintenance of chromatin structure in breast cancer cells, possibly in
      part through interaction with RNF40 and regulation of histone H2B
      monoubiquitination (H2Bub1). Moreover, we demonstrate that SUPT6H protein levels
      decrease with malignancy in breast cancer. Consistently, SUPT6H, similar to
      H2Bub1, is required for cellular differentiation and suppression of the
      repressive histone mark H3K27me3 on lineage-specific genes. Together, these data
      identify SUPT6H as a new epigenetic regulator of ERalpha activity and cellular
      differentiation. 

PMID- 24441045
TI  - Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes.
AB  - Activation of myofibroblast rich stroma is a rate-limiting step essential for
      cancer progression. The responsible factors are not fully understood, but
      TGFbeta1 is probably critical. A proportion of TGFbeta1 is associated with
      extracellular nano-vesicles termed exosomes, secreted by carcinoma cells, and the
      relative importance of soluble and vesicular TGFbeta in stromal activation is
      presented. Prostate cancer exosomes triggered TGFbeta1-dependent fibroblast
      differentiation, to a distinctive myofibroblast phenotype resembling stromal
      cells isolated from cancerous prostate tissue; supporting angiogenesis in vitro
      and accelerating tumour growth in vivo. Myofibroblasts generated using soluble
      TGFbeta1 were not pro-angiogenic or tumour-promoting. Cleaving heparan sulphate
      side chains from the exosome surface had no impact on TGFbeta levels yet
      attenuated SMAD-dependent signalling and myofibroblastic differentiation.
      Eliminating exosomes from the cancer cell secretome, targeting Rab27a, abolished
      differentiation and lead to failure in stroma-assisted tumour growth in vivo.
      Exosomal TGFbeta1 is therefore required for the formation of tumour-promoting
      stroma.

PMID- 24441047
TI  - Inflammation in coronary artery disease.
AB  - Coronary artery disease (CAD) is the leading cause of death in the United States.
      Although CAD was formerly considered a lipid accumulation-mediated disease, it
      has now been clearly shown to involve an ongoing inflammatory response. Advances
      in basic science research have established the crucial role of inflammation in
      mediating all stages of CAD. Today, there is convincing evidence that multiple
      interrelated immune mechanisms interact with metabolic risk factors to initiate,
      promote, and ultimately activate lesions in the coronary arteries. This review
      aims to provide current evidence pertaining to the role of inflammation in the
      pathogenesis of CAD and discusses the impact of inflammatory markers and their
      modification on clinical outcomes. 

PMID- 24441046
TI  - Dual role of SIRT1 in UVB-induced skin tumorigenesis.
AB  - The protein deacetylase SIRT1 regulates various pathways in metabolism, aging and
      cancer. However, the role of SIRT1 in skin cancer remains unclear. Here, using
      mice with targeted deletions of SIRT1 in their epidermis in both resistant B6 and
      sensitive SKH1 hairless backgrounds, we show that the role of SIRT1 in skin
      cancer development induced by ultraviolet B (UVB) radiation is dependent on its
      gene dose. Keratinocyte-specific heterozygous deletion of SIRT1 promotes UVB
      induced skin tumorigenesis, whereas homozygous deletion of SIRT1 suppresses skin
      tumor development but sensitizes the B6 mice to chronic solar injury. In mouse
      skin, SIRT1 is haploinsufficient for UVB-induced DNA damage repair and expression
      of xeroderma pigmentosum C (XPC), a protein critical for repairing UVB-induced
      DNA damage. As compared with normal human skin, downregulation of SIRT1 is in
      parallel with downregulation of XPC in human cutaneous squamous cell carcinoma at
      both the protein and mRNA levels. In contrast, homozygous SIRT1 deletion in mouse
      skin augments p53 acetylation and expression of its transcriptional target Noxa,
      and sensitizes the epidermis to UVB-induced apoptosis in vivo, while heterozygous
      SIRT1 deletion has no such effect. The gene dosage-dependent function of SIRT1 in
      DNA repair and cell survival is consistent with the dual roles of SIRT1 in UVB
      induced skin tumorigenesis. Our results reveal the gene dosage-dependent in vivo
      functions of SIRT1 in skin tumorigenesis and may shed light on the role of SIRT1
      in epithelial cancer induced by DNA damage.

PMID- 24441049
TI  - Multiferroic (ferroelastic/ferromagnetic/ferrimagnetic) aspects of phase
      transitions in RCo2 Laves phases.
AB  - Magnetic phase transitions in RCo2 Laves phases with R as a rare earth element
      are accompanied by changes in crystallographic space group. For purely structural
      transitions they would be described as improper ferroelastic and therefore fulfil
      the condition for multiferroic phase transitions in combining two out of three
      properties, ferro/antiferromagnetism, ferroelectricity and ferroelasticity. Here
      lattice parameter data from the literature and new measurements of elastic and
      anelastic properties, by resonant ultrasound spectroscopy, for NdCo2 and ErCo2
      have been analysed from this perspective. The temperature dependence of symmetry
      breaking shear strains is consistent with the cubic <-> tetragonal transition in
      NdCo2 being close to tricritical in character and the cubic <-> rhombohedral
      transition in ErCo2 being first order. Elastic softening and acoustic loss within
      the stability ranges of the ferroelastic phases can be understood in terms of a
      combination of intrinsic softening due to strain/order parameter coupling and
      ferroelastic twin-wall motion. Softening ahead of the transitions does not fit
      with standard macroscopic descriptions of dynamic effects from other systems but,
      rather, in the case of NdCo2, might be attributed to the involvement of a second
      zone centre order parameter related to a separate instability driven by
      cooperative Jahn-Teller distortions. In ErCo2, acoustic loss in the temperature
      interval above the transition point is discussed in terms of a possible tweed
      microstructure associated with strain coupling to local magnetic ordering. The
      overall multiferroic behaviour can be understood in terms of a single magnetic
      order parameter (irrep mGamma+4 of magnetic space group Fd3m1') which couples
      with a structural order parameter (irrep Gamma+3 or Gamma+5). The coupling is
      linear/quadratic which, in the case of two separate instabilities, causes them to
      combine in a single multiferroic phase transition.

PMID- 24441048
TI  - Association of aging, arterial stiffness, and cardiovascular disease: a review.
AB  - Coronary heart disease (CHD) is the leading cause of morbidity and mortality in
      the western world. Primary and secondary prevention strategies have improved
      tremendously. Conventional risk factors are identified and treated with intensive
      pharmacotherapy. Despite these measures, the incidence of CHD is on the rise in
      developed countries. Arterial stiffness has been identified as an independent
      risk factor for the development of CHD, both in the general population and in
      those with established CHD. This review examines the association of arterial
      stiffness with cardiovascular disease. 

PMID- 24441050
TI  - Burn injury, gender and cancer risk: population-based cohort study using data
      from Scotland and Western Australia.
AB  - OBJECTIVE: To investigate the risk of cancer and potential gender effects in
      persons hospitalised with burn injury. DESIGN: Population-based retrospective
      cohort study using record-linkage systems in Scotland and Western Australia.
      PARTICIPANTS: Records of 37 890 and 23 450 persons admitted with a burn injury in
      Scotland and Western Australia, respectively, from 1983 to 2008. Deidentified
      extraction of all linked hospital morbidity records, mortality and cancer records
      were provided by the Information Service Division Scotland and the Western
      Australian Data Linkage Service. MAIN OUTCOME MEASURES: Total and gender-specific
      number of observed and expected cases of total ('all sites') and site-specific
      cancers and standardised incidence ratios (SIRs). RESULTS: From 1983 to 2008, for
      female burn survivors, there was a greater number of observed versus expected
      notifications of total cancer with 1011 (SIR, 95% CI 1.3, 1.2 to 1.4) and 244
      (SIR, 95% CI 1.12, 1.05 to 1.30), respectively, for Scotland and Western
      Australia. No statistically significant difference in total cancer risk was found
      for males. Significant excesses in observed cancers among burn survivors
      (combined gender) in Scotland and Western Australian were found for buccal
      cavity, liver, larynx and respiratory tract and for cancers of the female genital
      tract. CONCLUSIONS: Results from the Scotland data confirmed the increased risk
      of total ('all sites') cancer previously observed among female burn survivors in
      Western Australia. The gender dimorphism observed in this study may be related to
      the role of gender in the immune response to burn injury. More research is
      required to understand the underlying mechanism(s) that may link burn injury with
      an increased risk of some cancers.

PMID- 24441051
TI  - Point-of-care assessment of platelet reactivity in the emergency department may
      facilitate rapid rule-out of acute coronary syndromes: a prospective cohort pilot
      feasibility study.
AB  - OBJECTIVE: Accurate, efficient and cost-effective disposition of patients
      presenting to emergency departments (EDs) with symptoms suggestive of acute
      coronary syndromes (ACS) is a growing priority. Platelet activation is an early
      feature in the pathogenesis of ACS; thus, we sought to obtain an insight into
      whether point-of-care testing of platelet function: (1) may assist in the rule
      out of ACS; (2) may provide additional predictive value in identifying patients
      with non-cardiac symptoms versus ACS-positive patients and (3) is logistically
      feasible in the ED. DESIGN: Prospective cohort feasibility study. SETTING: Two
      urban tertiary care sites, one located in the USA and the second in Argentina.
      PARTICIPANTS: 509 adult patients presenting with symptoms of ACS. MAIN OUTCOME
      MEASURES: Platelet reactivity was quantified using the Platelet Function Analyzer
      100, with closure time (seconds required for blood, aspirated under high shear,
      to occlude a 150 um aperture) serving as the primary endpoint. Closure times were
      categorised as 'normal' or 'prolonged', defined objectively as the 90th centile
      of the distribution for all participants enrolled in the study. Diagnosis of ACS
      was made using the standard criteria. The use of antiplatelet agents was not an
      exclusion criterion. RESULTS: Closure times for the study population ranged from
      47 to 300 s, with a 90th centile value of 138 s. The proportion of patients with
      closure times >=138 s was significantly higher in patients with non-cardiac
      symptoms (41/330; 12.4%) versus the ACS-positive cohort (2/105 (1.9%); p=0.0006).
      The specificity of 'prolonged' closure times (>=138 s) for a diagnosis of non
      cardiac symptoms was 98.1%, with a positive predictive value of 95.4%.
      Multivariate analysis revealed that the closure time provided incremental,
      independent predictive value in the rule-out of ACS. CONCLUSIONS: Point-of-care
      assessment of platelet reactivity is feasible in the ED and may facilitate the
      rapid rule-out of ACS in patients with prolonged closure times.

PMID- 24441052
TI  - The effect of maternal age and planned place of birth on intrapartum outcomes in
      healthy women with straightforward pregnancies: secondary analysis of the
      Birthplace national prospective cohort study.
AB  - OBJECTIVES: To describe the relationship between maternal age and intrapartum
      outcomes in 'low-risk' women; and to evaluate whether the relationship between
      maternal age and intrapartum interventions and adverse outcomes differs by
      planned place of birth. DESIGN: Prospective cohort study. SETTING: Obstetric
      units (OUs), midwifery units and planned home births in England. PARTICIPANTS: 63
      371 women aged over 16 without known medical or obstetric risk factors, with
      singleton pregnancies, planning vaginal birth. METHODS: Log Poisson regression
      was used to evaluate the association between maternal age, modelled as a
      continuous and categorical variable, and risk of intrapartum interventions and
      adverse maternal and perinatal outcomes. MAIN OUTCOME MEASURES: Intrapartum
      caesarean section, instrumental delivery, syntocinon augmentation and a composite
      measure of maternal interventions/adverse outcomes requiring obstetric care
      encompassing augmentation, instrumental delivery, intrapartum caesarean section,
      general anaesthesia, blood transfusion, third-degree/fourth-degree tear, maternal
      admission; adverse perinatal outcome (encompassing neonatal unit admission or
      perinatal death). RESULTS: Interventions and adverse maternal outcomes requiring
      obstetric care generally increased with age, particularly in nulliparous women.
      For nulliparous women aged 16-40, the risk of experiencing an intervention or
      adverse outcome requiring obstetric care increased more steeply with age in
      planned non-OU births than in planned OU births (adjusted RR 1.21 per 5-year
      increase in age, 95% CI 1.18 to 1.25 vs adjusted RR 1.12, 95% CI 1.10 to 1.15)
      but absolute risks were lower in planned non-OU births at all ages. The risk of
      neonatal unit admission or perinatal death was significantly raised in
      nulliparous women aged 40+ relative to women aged 25-29 (adjusted RR 2.29, 95% CI
      1.28 to 4.09). CONCLUSIONS: At all ages, 'low-risk' women who plan birth in a non
      OU setting tend to experience lower intervention rates than comparable women who
      plan birth in an OU. Younger nulliparous women appear to benefit more from this
      reduction than older nulliparous women.

PMID- 24441054
TI  - UK multiple sclerosis risk-sharing scheme: a new natural history dataset and an
      improved Markov model.
AB  - OBJECTIVES: In 2002, the UK's National Institute for Health and Care Excellence
      concluded that the multiple sclerosis (MS) disease modifying therapies;
      interferon-beta and glatiramer acetate, were not cost effective over the short
      term but recognised that reducing disability over the longer term might
      dramatically improve the cost effectiveness. The UK Risk-sharing Scheme (RSS) was
      established to ensure cost-effective provision by prospectively collecting
      disability-related data from UK-treated patients with MS and comparing findings
      to a natural history (untreated) cohort. However, deficiencies were found in the
      originally selected untreated cohort and the resulting analytical approach. This
      study aims to identify a more suitable natural history cohort and to develop a
      robust analytical approach using the new cohort. DESIGN: The Scientific Advisory
      Group, recommended the British Columbia Multiple Sclerosis (BCMS) database,
      Canada, as providing a more suitable natural history comparator cohort.
      Transition probabilities were derived and different Markov models (discrete and
      continuous) with and without baseline covariates were applied. SETTING: MS
      clinics in Canada and the UK. PARTICIPANTS: From the BCMS database, 898
      'untreated' patients with MS considered eligible for drug treatment based on the
      UK's Association of British Neurologists criteria. OUTCOME MEASURE: The predicted
      Expanded Disability Status Scale (EDSS) score was collected and assessed for
      goodness of fit when compared with actual outcome. RESULTS: The BCMS untreated
      cohort contributed 7335 EDSS scores over a median 6.4 years (6357 EDSS
      'transitions' recorded at consecutive visits) during the period 1980-1995. A
      continuous Markov model with 'onset age' as a binary covariate was deemed the
      most suitable model for future RSS analysis. CONCLUSIONS: A new untreated MS
      cohort from British Columbia has been selected and will be modelled using a
      continuous Markov model with onset age as a baseline covariate. This approach
      will now be applied to the treated UK RSS MS cohort for future price adjustment
      calculations.

PMID- 24441055
TI  - Assessment of the quality of reporting for treatment components in Cochrane
      reviews of acupuncture.
AB  - OBJECTIVES: High-quality reporting of treatment details can aid replication of
      study results in real-world clinical practice. The Standards for Reporting
      Interventions in Clinical Trials of Acupuncture (STRICTA) is a reporting
      guideline for key elements of acupuncture interventions in clinical trials. This
      study used STRICTA to investigate whether Cochrane reviews of acupuncture
      adequately report important treatment details. DESIGN: Systematic review METHODS:
      Cochrane reviews of acupuncture were identified from The Cochrane Library (issue
      7, 2012). Randomised controlled trials (RCTs) included in the reviews and
      published after 2005 were obtained. Using STRICTA, we extracted acupuncture
      related information from the Cochrane reviews and the RCTs. The characteristics
      of the included studies' table were the major source of intervention information
      from Cochrane reviews. Reporting quality of acupuncture interventions in Cochrane
      reviews was assessed and compared with the respective RCTs. RESULTS: 25 Cochrane
      reviews of acupuncture and 92 RCTs met the selection criteria. Cochrane reviews
      were 16% less likely to report the acupuncture-related items of STRICTA than RCTs
      (risk ratio 0.84, 95% CI 0.79 to 0.88, I(2)=8%). Information was significantly
      better reported for 10 of the 15 treatment-group items of STRICTA in RCTs than in
      Cochrane reviews (p<0.05), while four items did so without statistical
      significance. One item related to practitioner background was significantly
      better reported in Cochrane reviews. CONCLUSIONS: Reporting quality of treatment
      details in Cochrane reviews of acupuncture was insufficient with regard to
      STRICTA, even though such information was readily reported in RCTs. The overall
      quality of reporting of the RCTs, while better than the reviews, was also often
      suboptimal. Use of STRICTA guideline during the review process is recommended to
      adequately report the key treatment components in Cochrane reviews of
      acupuncture. The potential impact of STRICTA to the replicability and utilisation
      of reviews in future research and practice needs to be investigated.

PMID- 24441056
TI  - Childhood socioeconomic position, young adult intelligence and fillings of
      prescribed medicine for prevention of cardiovascular disease in middle-aged men.
AB  - OBJECTIVES: To explore the relationship between childhood socioeconomic position
      (SEP) and filling of medicine prescriptions for prevention of cardiovascular
      diseases (CVDs), with young adult intelligence (IQ) as a potential mediator.
      DESIGN: Birth cohort study with logistic and Cox-proportional hazard regression
      analyses of associations between childhood SEP, retrieved from birth
      certificates, and prevalence, initiation of and refill persistency for CVD
      preventive medicine. SETTING: Denmark. PARTICIPANTS: 8736 Danish men born in
      1953, who had no CVD at the start of follow-up in 1995, were followed in the
      Danish National Prescription Register for initiation of and refill persistency
      for antihypertensives and statins, until the end of 2007 (age 54 years). RESULTS:
      Low childhood SEP at age 18 was not associated with prescription fillings of
      antihypertensives, but was weakly associated with initiation of statins (HR =
      1.19 (95% CI 1.00 to1.42)). This estimate was attenuated when IQ was entered into
      the model (HR=1.10 (95% CI 0.91 to 1.23)). Low childhood SEP was also associated
      with decreased refill persistency for statins (HR=2.23 (95% CI 1.13 to 4.40)).
      Thus, the HR for SEP only changed slightly (HR=2.24 (95% CI 1.11 to 4.52)) when
      IQ was entered into the model, but entering other covariates (education and body
      mass index in young adulthood and income in midlife) into the model attenuated
      the HR to 2.04 (95% CI 1.00 to 4.16). CONCLUSIONS: Low childhood SEP was related
      to more frequent initiation of and poorer refill persistency for statins. IQ in
      young adulthood explained most of the association between childhood SEP and
      initiation of statins, but had no impact on refill persistency.

PMID- 24441057
TI  - Calculating the burden of disease of avian-origin H7N9 infections in China.
AB  - OBJECTIVE: A total of 131 cases of avian-originated H7N9 infection have been
      confirmed in China mainland from February 2013 to May 2013. We calculated the
      overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of
      comprehensive burden of disease in the 21st century from an acute animal-borne
      emerging infectious disease. DESIGN: We present an accurate and operable method
      for estimating the burden of H7N9 cases in China. The main drivers of economic
      loss were identified. Costs were broken down into direct (outpatient and
      inpatient examination and treatment) and indirect costs (cost of disability
      adjusted life years (DALYs) and losses in the poultry industry), which were
      estimated based on field surveys and China statistical year book. SETTING: Models
      were applied to estimate the overall burden of H7N9 cases in China. PARTICIPANTS:
      131 laboratory-confirmed H7N9 cases by 31 May 2013. OUTCOME MEASURE: Burden of
      H7N9 cases including direct and indirect losses. RESULTS: The total direct
      medical cost was Y16 422 535 (US$2 627 606). The mean cost for each patient was
      Y10 117 (US$1619) for mild patients, Y139 323 (US$22 292) for severe cases
      without death and Y205 976 (US$32 956) for severe cases with death. The total
      cost of DALYs was Y17 356 561 (US$2 777 050). The poultry industry losses
      amounted to Y7.75 billion (US$1.24 billion) in 10 affected provinces and Y3.68
      billion (USD$0.59 billion) in eight non-affected adjacent provinces. CONCLUSIONS:
      The huge poultry industry losses followed live poultry markets closing down and
      poultry slaughtering in some areas. Though the proportion of direct medical
      losses and DALYs losses in the estimate of H7N9 burden was small, the medical
      costs per case were extremely high (particularly for addressing the use of modern
      medical devices). A cost-effectiveness assessment for the intervention should be
      conducted in a future study.

PMID- 24441058
TI  - Long-term mortality after community-acquired sepsis: a longitudinal population
      based cohort study.
AB  - OBJECTIVE: Prior studies have concentrated on the acute short-term outcomes of
      sepsis, with little focus on its long-term consequences. The objective of this
      study was to characterise long-term mortality following a sepsis event. DESIGN:
      Population-based data from the 30 239 community-dwelling individuals in the
      REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. SETTING
      USA PARTICIPANTS: Community-dwelling adults >=45 years of age. Sepsis was defined
      as hospitalisation or emergency department treatment for a serious infection with
      the presence of >=2 systemic inflammatory response syndrome criteria. OUTCOMES: 6
      year all-cause mortality. The analysis utilised a time-varying Cox model adjusted
      for participant's age, demographic factors, health behaviours and chronic medical
      conditions. RESULTS: The participants were observed for a median of 6.1 years
      (IQR 4.5-7.1). During this period, 975 individuals experienced a sepsis event.
      Sepsis hospital mortality was 8.9%. One-year, 2-year and 5-year all-cause
      mortality among individuals with sepsis were 23%, 28.8% and 43.8%, respectively,
      compared with death rates of 1%, 2.6% and 8.3% among those who never developed
      sepsis. On multivariable analysis, the association of sepsis with increased all
      cause mortality persisted for up to 5 years, after adjustment for confounders;
      year 0.00-1.00, adjusted HR (aHR) 13.07 (95% CI 10.63 to 16.06); year 1.01-2.00
      aHR 2.64 (1.85 to 3.77); year 2.01-3.00 aHR 2.18 (1.43 to 3.33); year 3.01-4.00
      aHR 1.97 (1.19 to 3.25); year 4.01-5.00 aHR 2.08 (1.14 to 3.79); year 5.01+ aHR
      1.41 (0.67 to 2.98). CONCLUSIONS: Individuals with sepsis exhibited increased
      rates of death for up to 5 years after the illness event, even after accounting
      for comorbidities. Sepsis is independently associated with increased risk of
      mortality well after hospital treatment.

PMID- 24441059
TI  - Impact of subsidence on clinical outcomes and radiographic fusion rates in
      anterior cervical discectomy and fusion: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To provide a systematic review of
      published literature on the impact of subsidence on clinical outcomes and
      radiographic fusion rates after anterior cervical discectomy and fusion with
      plates or without plates. BACKGROUND: Subsidence of interbody implants is common
      after anterior cervical spine fusions. The impact of subsidence on fusion rates
      and clinical outcomes is unknown. METHODS: Systematic literature review on
      published articles on anterior cervical discectomy and fusion, which objectively
      measured graft subsidence, radiographic fusion rates, and clinical outcomes
      between April 1966 and December 2010. RESULTS: A total of 35 articles that
      measured subsidence and provided fusion rates and/or clinical outcomes were
      selected for inclusion. The mean subsidence rate ranged from 19.3% to 42.5%. The
      rate of subsidence based on the type of implant ranged from 22.8% to 35.9%. The
      incidence of subsidence was not impacted by the type of implant (P=0.98). The
      overall fusion rate of the combined studies was 92.8% and was not impacted by
      subsidence irrespective of subsidence definition or the measurement technique
      used (P=0.19). Clinical outcomes were evaluated in 27 of 35 studies with all
      studies reporting an improvement in patient outcomes postoperatively.
      CONCLUSIONS: Subsidence irrespective of the measurement technique or definition
      does not appear to have an impact on successful fusion and/or clinical outcomes.
      A validated definition and standard measurement technique for subsidence is
      needed to determine the actual incidence of subsidence and its impact on
      radiographic and clinical outcomes.

PMID- 24441061
TI  - From the editor.

PMID- 24441060
TI  - Radiation exposure for fluoroscopy-guided lumbosacral epidural steroid
      injections: comparison of the transforaminal and caudal approaches.
AB  - STUDY DESIGN: A retrospective investigation. OBJECTIVE: We evaluated and compared
      the radiation exposure caused by using the fluoroscopy-guided transforaminal and
      caudal approaches of lumbosacral epidural steroid injection (ESI). SUMMARY OF
      BACKGROUND DATA: Only a few studies focused on the radiation exposure to patients
      who underwent lumbosacral ESI for pain management. MATERIALS AND METHODS: A total
      of 228 patients (83 males, 145 females; mean age, 63.3 y) who received
      lumbosacral ESI were included. Transforaminal ESI was performed in 181 patients
      (67 males, 114 females; mean age, 61.3 y) and caudal ESI was used in 47 patients
      (16 males, 31 females; mean age, 69.7 y). All ESIs were performed under a single
      plane fluoroscopic guidance by 1 musculoskeletal radiologist. The kerma-area
      product (KAP) and fluoroscopy time were recorded in all patients. Both
      measurements were correlated and compared for each approach. RESULTS: KAP was
      3.02-1048.2 MUGy m (mean, 101.7 MUGy m; median, 67.8 MUGy m) for transforaminal
      ESI and 16.0-604.5 MUGy m (mean, 101.8 MUGy m; median, 54.6 MUGy m) for caudal
      ESI. The fluoroscopy time was 11-161 seconds for transforaminal ESI (mean, 36.0
      s; median, 29 s) and 4-78 seconds (mean, 18.2 s; median, 13 s) for caudal ESI.
      KAP and fluoroscopy time were positively correlated for each approach (P<0.001).
      Fluoroscopy time was significantly longer for transforaminal ESI (correlation
      coefficient=-0.77, P=0.000). After correction for the fluoroscopy time, KAP was
      less in transforaminal ESI than in caudal ESI (correlation coefficient=0.74,
      P=0.000). CONCLUSIONS: The longer the fluoroscopy time, the greater the KAP in
      both transforaminal and caudal ESIs. The fluoroscopy time for transforaminal ESI
      was longer than that for caudal ESI. However, KAP of transforaminal ESI was less
      than that of the caudal ESI, after being corrected for the length of fluoroscopy
      time.

PMID- 24441062
TI  - Vocational integration: Dream or reality?
AB  - The simple lifestyle of non-industrialized societies is used to remind us of the
      essential principles underpinning vocational integration. Best practice in
      Western societies would seem to heed these principles. Examples are given that
      can be used to guide and improve practice. 

PMID- 24441063
TI  - Access to work: Employment services for people with disabilities in Scotland.
AB  - Employment services, including work rehabilitation, for people with disabilities
      have traditionally been delivered through the voluntary and public sectors in
      Scotland. The three main statutory agencies are the Department of Employment, the
      National Health Service, and the Social Work Department. Although occupational
      therapy is an established component of work rehabilitation programs in several
      countries (e.g., the United States, Canada, and Australia), it is a comparatively
      small area of practice in Scotland. However, recent changes in health and social
      service development, proposed changes to government benefits schemes, as well as
      health and safety legislation are among the factors that will influence the
      continued development and expansion of employment services. As such, occupational
      therapy practitioners will need to look to the public, private, and voluntary
      sectors as potential new purchasers and employers to bring their skills to this
      area of professional practice. 

PMID- 24441064
TI  - Personal injury compensation cases in the United Kingdom: The use of American
      vocational assessment tools in personal injury compensation.
AB  - This article describes the role of vocational assessment in personal injury
      compensation cases in the United Kingdom. An outline is given of some of the
      difficulties the writer has confronted in getting vocational assessment accepted
      as a legitimate resource in such cases, and the rationale for using American
      vocational assessment tools is presented. Finally, reference is made to two key
      legal rulings. The first ruling threatened the use of vocational assessment, and
      the second went some way toward redressing the balance. 

PMID- 24441065
TI  - A short course in work assessment for occupational therapists in Taiwan.
AB  - This article outlines a required prevocational assessment course taken by
      occupational therapy students in Taiwan. Course objectives are to teach basic
      concepts in work assessment and intervention and provide practical ways of using
      these concepts in clinical practice. The course content is reviewed; it includes
      standardized tests; job analysis, vocational evaluation, and work adjustment
      checklists and report forms; adaptive assessment; clinical observations; and case
      studies. The scope of practice for occupational therapists in vocational
      evaluation is also discussed. 

PMID- 24441066
TI  - ADL abilities and vocational competencies: Blue-collar workers aged 45 years and
      over.
AB  - A questionnaire composed of 55 items that addressed activities of daily living
      (ADL) abilities and 13 basic vocational competencies, such as memory and muscular
      power, was completed by 48 nondisabled male workers aged >=45 years. The workers
      were all engaged in the manufacturing industry. All respondents found the
      following five tasks easy to do: wring a towel, put arms through sleeves, open
      and shut a door, turn a tap on and off, and open and shut a sliding door. Among
      basic vocational competencies, the highest performance, with but a small standard
      deviation, occurred with the muscular power competency; a low performance with a
      large standard deviation (P=0.05) occurred with concentration. No age difference
      was discerned in planning ability, cooperativeness, muscular power, staying
      power, manual adeptness, and sense of equilibrium, whereas in learning ability,
      agility, and concentration, people aged >=65 years showed significantly lower
      performance (P=0.05). The characteristics of vocational competencies in
      manufacturing industry workers aged >=45 years were fond to be linked to ADL
      abilities, and the effectiveness of the ADL abilities survey, prepared on an
      experimental basis, was confirmed for the evaluation of vocational competencies. 

PMID- 24441067
TI  - Disability Leave: Developing a policy for use when an employee develops a
      disability.
AB  - This article describes the launch of Disability Leave as a pilot policy in the
      United Kingdom. The nature and purpose of Disability Leave and the nature of the
      pilot program are discussed. Some implications of Disability Leave for employees,
      employers, and disability services, as well as national and international
      implications, are presented. 

PMID- 24441068
TI  - Mental health work rehabiliation services in the United States-innovation and
      good practice.
AB  - During the spring of 1994, the author visited innovative and good practice,
      mental health rehabilitation schemes in the United States. Current practice and
      the training of staff especially in the field of work rehabilitation, was
      observed, and comments are made on the positive features of these exemplary
      schemes and their programs. There are both striking similarities and differences
      in the philosophy and delivery of mental health work rehabilitation services in
      the United States and United Kingdom. The move away from the traditional workshop
      model to placing people in competitive employment, strongly emphasized in the
      United States in recent years, has shown promising results. The employment models
      used, and their relevance to services in the United Kingdom, are discussed. Ideas
      and information generated by the visit will be used to develop work
      rehabilitation services within the author's organization and in Oxfordshire as a
      whole. 

PMID- 24441069
TI  - The male minority: Job satisfaction of men in occupational therapy.
AB  - Occupational therapy is a female dominated profession: only 3% of all clinicians
      are men. The purpose of this investigation was to identify variables that affect
      the job satisfaction of male occupational therapists. Specifically, the study
      examined five job satisfaction factors (work, pay, coworkers, supervision, and
      promotional opportunities), work environment traits, community role strain,
      colleague role strain, patient role strain, role ambiguity, role conflict, role
      overload, and specific demographic characteristics of male occupational
      therapists. A mailed survey questionnaire was sent to all male clinicians who
      were members of the Canadian Association of Occupational Therapists (n = 199)
      during the 1990-1991 membership year. Eighty-three percent of the sample
      responded (n = 164). Of these, 74% said they expect to leave the occupational
      therapy profession within 10 years. Most male occupational therapists reside in
      Ontario, are 33 years old, work with an adult client case load in a general
      hospital setting, and spend half their time in direct client care. Respondents
      indicated that, as a group, they are very dissatisfied with their work, pay,
      promotional opportunities, supervision, and coworkers. Male occupational
      therapists rated their work environments as above average in terms of physical
      comfort, but below average for control. As a group, male occupational therapists
      experience an average level of community, colleague, and patient role strain.
      Similarly, they experience an average degree of role conflict and role overload,
      but reported a low level of role ambiguity. Significant predictors of
      respondents' global job satisfaction were examined by multiple regression
      analysis. Five factors were determined to be significant predictors of global job
      satisfaction: community role strain, number of hours of overtime worked on a
      weekly basis, involvement, year of graduation from professional training, and
      colleague role strain. Recommendations for occupational therapy personnel and
      future research are made based on these results. 

PMID- 24441070
TI  - A survey of continued productive activity in those over the expected retirement
      age.
AB  - This article discusses the results of a study done in England that examined the
      activity involvement of people >60 years of age. Data were gathered through
      surveying two local newspapers, face- to face contacts, telephone calls, and
      letters. Areas examined included health and community welfare, education,
      politics, legal matters, religious affairs, businesses, environmental issues, and
      creative activity. Results found that many of the community's older people are
      productively occupied in these various areas. Positive and negative influences on
      their involvement are discussed, us well as ways of increasing older people's
      involvement in the future. 

PMID- 24441073
TI  - Notes on testing equality and interval estimation in Poisson frequency data under
      a three-treatment three-period crossover trial.
AB  - When the frequency of event occurrences follows a Poisson distribution, we
      develop procedures for testing equality of treatments and interval estimators for
      the ratio of mean frequencies between treatments under a three-treatment three
      period crossover design. Using Monte Carlo simulations, we evaluate the
      performance of these test procedures and interval estimators in various
      situations. We note that all test procedures developed here can perform well with
      respect to Type I error even when the number of patients per group is moderate.
      We further note that the two weighted-least-squares (WLS) test procedures derived
      here are generally preferable to the other two commonly used test procedures in
      the contingency table analysis. We also demonstrate that both interval estimators
      based on the WLS method and interval estimators based on Mantel-Haenszel (MH)
      approach can perform well, and are essentially of equal precision with respect to
      the average length. We use a double-blind randomized three-treatment three-period
      crossover trial comparing salbutamol and salmeterol with a placebo with respect
      to the number of exacerbations of asthma to illustrate the use of these test
      procedures and estimators.

PMID- 24441074
TI  - On the importance of identifying, characterizing, and predicting fundamental
      phenomena towards microbial electrochemistry applications.
AB  - The development of microbial electrochemistry research toward technological
      applications has increased significantly in the past years, leading to many
      process configurations. This short review focuses on the need to identify and
      characterize the fundamental phenomena that control the performance of microbial
      electrochemical cells (MXCs). Specifically, it discusses the importance of recent
      efforts to discover and characterize novel microorganisms for MXC applications,
      as well as recent developments to understand transport limitations in MXCs. As we
      increase our understanding of how MXCs operate, it is imperative to continue
      modeling efforts in order to effectively predict their performance, design
      efficient MXC technologies, and implement them commercially. Thus, the success of
      MXC technologies largely depends on the path of identifying, understanding, and
      predicting fundamental phenomena that determine MXC performance. 

PMID- 24441076
TI  - The effectiveness of pressure ulcer risk assessment instruments and associated
      intervention protocols remains uncertain.

PMID- 24441075
TI  - Discovery of a structural-element specific G-quadruplex "light-up" probe.
AB  - The development of a fluorescent probe capable of detecting and distinguishing
      the wide diversity of G-quadruplex structures is particularly challenging.
      Herein, we report a novel BODIPY-based fluorescent sensor (GQR) that shows
      unprecedented selectivity to parallel-stranded G-quadruplexes with exposed ends
      and four medium grooves. Mechanistic studies suggest that GQR associates with G
      quadruplex grooves close to the end of the tetrad core, which may explain the
      dye's specificity to only a subset of parallel structures. This specific
      recognition favours the disaggregation of GQR in aqueous solutions thereby
      recovering the inherent fluorescence of the dye. Due to its unique features, GQR
      represents a valuable tool for basic biological research and the rapid discovery
      of novel, specific ligands that target similar structural features of G
      quadruplexes. 

PMID- 24441077
TI  - Delayed prescription worsens reported symptoms and increases antibiotic use
      compared with clinical score with or without rapid antigen testing in patients
      with sore throat.

PMID- 24441078
TI  - More evidence for the benefits of cognitive activity over the lifespan.

PMID- 24441079
TI  - The addition of nebulised magnesium to the standard asthma therapy for children
      with severe symptoms results in small improvements in asthma severity scores.

PMID- 24441080
TI  - Polykrikos tanit sp. nov., a new mixotrophic unarmoured pseudocolonial
      dinoflagellate from the NW Mediterranean Sea.
AB  - Pigmented pseudocolonies initially identified as Polykrikos hartmannii Zimmermann
      were detected at several locations of the Catalan coast (NW Mediterranean Sea) in
      April-June of 2012 and April-May of 2013. To further explore the several
      remarkable morphological discrepancies between these organisms and P. hartmannii,
      we carried out a detailed morphological study and used single-cell PCR to obtain
      partial LSU and SSU rDNA sequences. The resulting phylogenies showed that our
      isolates occupy a basal position within the Polykrikos clade, close to P.
      hartmannii, but do not correspond to any described polykrikoid species. P.
      barnegatensis Martin is controversially considered to be synonymous with P.
      hartmannii. The organisms studied in this work were similar to P. barnegatensis
      but showed significant morphological differences with its original description
      such as the torsion of the pseudocolony, more pronounced overhanging of the
      cingula, stepped fusion border of the zooids, and number and shape of nuclei.
      Consequently, we propose that the isolates constitute a new species, which we
      named Polykrikos tanit sp. nov. The observed characters, pigmented, same number
      of zooids and nuclei, sulci not fused, and its phylogeny suggest that the species
      is an early evolutionary Polykrikos species. 

PMID- 24441082
TI  - Reactions of ruthenium hydrides with ethyl-vinyl sulfide.
AB  - The Ru-hydride precursors (Im(OMe)2)(PPh3)2RuHCl () and (Me2Im(OMe)2)(PPh3)2RuHCl
      () reacted with ethyl-vinyl-sulfide to give
      ((MeOCH2CH2)C3H2N2(CH2CH(OMe))RuCl(PPh3)2 () and
      ((MeOCH2CH2)C3Me2N2(CH2CH(OMe))RuCl(PPh3)2 (), respectively. Dissolution of () in
      C6D6 prompts formation of ((MeOCH2CH2)C5H6N2(CHCH)RuCl(PPh3)2 (). The analogous
      reactions of the bis-carbene Ru-hydride precursors (Im(OMe)2)(IMes)(PPh3)RuHCl
      (), (Im(OMe)2)(SIMes)(PPh3)RuHCl () and (Im(OMe)2)(IMes-Cl2)(PPh3)RuHCl () gave
      ((MeOCH2CH2)C3H2N2(CHCH)RuCl(PPh3)(NHC) (NHC = IMes (), SIMes (), IMes-Cl2 (),
      respectively. The formation of compounds () and () is thought to go through an
      initial insertion of the vinyl-fragment into the Ru-H prompting subsequent C-H
      activation and loss of diethyl sulfide. This yields () and (), while subsequent
      loss of methanol yields () and (-). 

PMID- 24441081
TI  - Assessment of chemical modifications of sites in the CDRs of recombinant
      antibodies: Susceptibility vs. functionality of critical quality attributes.
AB  - Modifications like asparagine deamidation, aspartate isomerization, methionine
      oxidation, and lysine glycation are typical degradations for recombinant
      antibodies. For the identification and functional evaluation of antibody critical
      quality attributes (CQAs) derived from chemical modifications in the
      complementary-determining regions (CDRs) and the conserved regions, an approach
      employing specific stress conditions, elevated temperatures, pH, oxidizing
      agents, and forced glycation with glucose incubation, was applied. The
      application of the specific stress conditions combined with ion exchange
      chromatography, proteolytic peptide mapping, quantitative liquid chromatography
      mass spectrometry, and functional evaluation by surface plasmon resonance
      analysis was adequate to identify and functionally assess chemical modification
      sites in the CDRs of a recombinant IgG1. LC-Met-4, LC-Asn-30/31, LC-Asn-92, HC
      Met-100c, and HC Lys-33 were identified as potential CQAs. However, none of the
      assessed degradation products led to a complete loss of functionality if only one
      light or heavy chain of the native antibody was affected. 

PMID- 24441083
TI  - Sucking-pads and primitive sucking reflex.
AB  - Sucking pads are hyperkeratotic thickenings of the inner aspect of the vermillion
      border of the lips of neonates. They develop around the 25th week of gestation
      and are the result of the primitive sucking reflex which is brain-stem mediated.
      The presence of sucking pads at birth represents an effective sucking reflex and
      as such it is recommended as a screening tool that indicates an intact motor
      neuron function in neonates. 

PMID- 24441084
TI  - Supplemental protein and postnatal growth of very low birth weight infants: a
      randomized trial.
AB  - BACKGROUND: Providing adequate nutritional support to promote optimal postnatal
      growth for very low birth weight (VLBW) infants has been a difficult problem to
      surmount in the NICU. During the past 4 decades, improvements in neonatal
      critical care have made it possible for more VLBW infants to survive to discharge
      from NICUs. The NICHD Neonatal Network reported that while intrauterine growth
      restriction was present in 22% of VLBW infants at birth, 91% demonstrated
      postnatal growth restriction by 36 weeks post menstrual age. The persistence of
      this nearly universal growth deficit is associated with the inadequacy of protein
      and energy intake, which may account for 45-50% of the postnatal growth
      restriction. OBJECTIVE: The purpose of this study was to assess whether
      increasing enteral intake, using supplemental protein, would improve postnatal
      growth for VLBW infants. STUDY DESIGN: Randomized clinical trial. Sixty-four
      infants were enrolled (34 in control group with 15 infants <1000 g, and 30 in
      intervention group with 13 infants <1000 g). RESULT: There were no sustained
      statistical differences between weekly measurements of weight, length, head
      circumference, and skinfold thickness between groups. There were no significant
      differences between laboratory results except blood urea nitrogen at time of peak
      protein intake for intervention group. CONCLUSIONS: Supplemental enteral protein
      had minimal to no effect on postnatal weight, length, head circumference, body
      mass, or length of stay. It may be most important to provide consistent sustained
      nutritional support with protein from birth to reduce postnatal growth
      restriction, especially for those infants <1000 g at birth.

PMID- 24441085
TI  - Effect of lullaby and classical music on physiologic stability of hospitalized
      preterm infants: a randomized trial.
AB  - BACKGROUND: Music is considered a subset of developmental supportive care. It may
      act as a suitable auditory stimulant in preterm infants. Also, it may reduce
      stress responses in autonomic, motor and state systems. OBJECTIVE: To assess and
      compare the influence of lullaby and classical music on physiologic parameters.
      METHOD: This is a randomized clinical trial with cross-over design. A total of 25
      stable preterm infants with birth weight of 1000-2500 grams were studied for six
      consecutive days. Each infant was exposed to three phases: lullaby music,
      classical music, and no music (control) for two days each. The sequence of these
      phases was assigned randomly to each subject. Babies were continuously monitored
      for heart rate, respiratory rate, and oxygen saturation and changes between
      phases were analyzed. RESULT: Lullaby reduced heart rate (p < 0.001) and
      respiratory rate (p = 0.004). These effects extended in the period after the
      exposure (p < .001 and p = 0.001, respectively). Classical music reduced heart
      rate (p = 0.018). The effects of classical music disappeared once the music
      stopped. Oxygen saturation did not change during intervention. CONCLUSION: Music
      can affect vital signs of preterm infants; this effect can possibly be related to
      the reduction of stress during hospitalization. The implications of these
      findings on clinical and developmental outcomes need further study.

PMID- 24441086
TI  - Breastfeeding initiation in women with gestational diabetes mellitus.
AB  - BACKGROUND: In the United States, breastfeeding initiation (BFI) is reported for
      75% of all live births; however, little information is available regarding
      mothers affected by gestational diabetes mellitus (GDM). OBJECTIVE: To examine
      feeding practices and factors associated with BFI in women with GDM and their
      infants. METHODS: A total of 303 GDM (58 late preterm and 245 term) pregnancies
      were studied. Infant feeding preference was ascertained on admission to labor and
      delivery. Variables known to influence BFI including maternal age, smoking,
      obesity, racial and educational characteristics were assessed. RESULTS: On
      admission 188 women intended to BF, 60 intended to feed formula and 55 were
      undecided. None of the women who wished to feed formula and 27% of the originally
      undecided later initiated BF. Regardless of feeding preference 163 (54%) of all
      mothers initiated BF. Similar BFI rates were found for 176 Class A1 and 127 class
      A2 women. Logistic regression analysis showed that intention to BF was the most
      significant predictor of BFI. Factors associated with BFI failure included
      African American race, lower education, smoking, obesity and admission to NICU.
      Following delivery 264 (87%) infants received well baby care while 39 (13%) were
      admitted to the NICU. Among 188 women who intended to BF, BFI involved 81% of 160
      infants receiving well baby care and 61% of the 28 admitted to the NICU.
      CONCLUSIONS: More than half of women with GDM, who intended to BF, initiated BF.
      BFI failure remains associated with race, lower education level, smoking,
      obesity, preference for formula feeding and admission to NICU.

PMID- 24441087
TI  - Risk factors for the development of necrotizing enterocolitis: a case-control
      study.
AB  - AIM: To determine risk or protective factors for the development of necrotizing
      enterocolitis in very low birth weight infants. METHODS: This retrospective case
      control study was conducted at La Paz University Hospital including infants with
      a birth weight of <1500 g for three years. Cases with confirmed diagnosis of
      necrotizing enterocolitis were evaluated; each one was paired with a control
      infant of the same gestational age. Statistical analysis included unadjusted and
      multivariable analyses. RESULTS: A total of 576 very low birth weight infants
      were admitted; of them 30 infants (5.2%) developed necrotizing enterocolitis. The
      main clinical and demographic characteristics did not differ between the two
      groups. The frequency of infants transfused with packed red blood cells was
      similar in cases (63%) and control patients (77%). However, a greater number of
      transfusions increased the odds of necrotizing enterocolitis [OR 1.5, 95%CI (1.01
      to 2.24)]. CONCLUSIONS: A greater number of transfusions of packed red blood
      cells are associated with an increased risk of necrotizing enterocolitis in very
      low birth weight infants. The other analyzed variables in this study do not
      identify the infants at risk. Caution is advocated in using transfusions in
      newborns.

PMID- 24441088
TI  - Individualizing fortification of human milk using real time human milk analysis.
AB  - OBJECTIVE: To use real-time human milk macronutrient analysis to calculate final
      composition following fortification. STUDY DESIGN: Preterm HM (PHM) and pooled
      donor human milks (DHM) were analyzed by mid-infrared spectroscopy for protein,
      fat and lactose. Energy content was calculated from macronutrient results. Three
      lactation stages were constructed. DHM was compared to PHM. Four milk sample
      profiles were selected to demonstrate individualized fortification results.
      RESULTS: Lactose was similar in PHM and DHM. Protein in PHM showed the expected
      decline as lactation progressed. DHM protein was significantly lower vs. PHM. Fat
      was highly variable and lowest in DHM. Using standard fortification protocols,
      not all fortified milks met targets for protein and energy. Individualized
      fortification resulted in milks closer to target recommendations. CONCLUSIONS:
      Real-time analysis of HM provides assessment of the macronutrient content of the
      milk and can guide fortification. Individualized protocols, based on actual milk
      macronutrient profiles, may need to be considered to avoid unexpected nutrient
      content.

PMID- 24441089
TI  - Antimicrobial prescription and usage in the neonatal intensive care units of a
      Caribbean country: a prospective observational study.
AB  - OBJECTIVE: To study the prescribing patterns and usage of antimicrobials in the
      Neonatal Intensive Care Units (NICU) of Trinidad & Tobago. METHODS: A 3-month
      prospective observational study was conducted at the three NICUs at the major
      public hospitals. Data included antimicrobials prescribed, route of
      administration, culture and sensitivity reports, leukocyte count, length of stay
      and outcome of patients. RESULTS: 353 patients were studied, 57.5% of the
      patients were males. Mean birth weight was 2.96 +/- 0.94 (Standard Deviation) kg.
      Admission diagnoses included meconium stained liquor, preterm, respiratory
      distress, sepsis, etc. Length of stay ranged between 1 to 76 days, (median 4,
      Interquartile Range 1-8). The mean leukocyte count was 15.7 +/- 8.5 * 103 per
      MUL. Overall, 645 culture specimens were sent; umbilical swab (27.6%), throat
      swab (27.0%) and blood (16.4%) being the most common specimens. 310 (48.1%)
      showed no bacterial growth. Overall, 16 different antimicrobials were used. First
      line antibiotic of choice was a combination of ampicillin and gentamicin (85.8
      %). Second line antibiotic of choice was cefotaxime. The overall mortality was
      7.6%. CONCLUSION: The choice of antimicrobials in the NICUs of major public
      hospitals is mostly empirical and not primarily dictated by the culture and
      sensitivity reports, emphasizing the need for antibiotic stewardship programme in
      Trinidad & Tobago.

PMID- 24441090
TI  - Evaluating patterns of morphine use in a neonatal intensive care unit after
      NEOPAIN.
AB  - OBJECTIVE: To test the hypothesis that use of morphine for sedation of ventilated
      premature neonates has not changed despite evidence-based recommendations. STUDY
      DESIGN: Retrospective chart review. RESULTS: Of 410 ventilated patients, 129
      received a morphine infusion. The annual percentage of ventilated patients
      started on an infusion did not vary significantly from 2005-2010 (range: 27%-37%,
      mean: 32%, chi2 test for trend p = 0.60). Patients given morphine infusion had a
      lower median estimated gestational age at birth (26 0/7 weeks versus 27 6/7
      weeks), and a lower median birth weight (762 versus 1010 grams). CONCLUSION: Use
      of morphine as a sedative and/or pre-emptive analgesic agent for critically ill,
      ventilated, premature neonates has not decreased at the study site despite
      evidence-based recommendations against this treatment approach. This is an area
      of care that may benefit from quality improvement interventions.

PMID- 24441091
TI  - Volume targeted ventilation and arterial carbon dioxide in extremely preterm
      infants.
AB  - AIM: The aim of our study was to quantify arterial carbon dioxide levels (PaCO2)
      achieved by ventilating extremely preterm neonates in volume guarantee mode
      targeting tidal volumes of approximately 4 ml/kg. METHODS: We performed a
      prospective trial on preterm infants with gestational age <=28 weeks, birth
      weight <=1000 grams, postnatal age <48 hours and are supported by mechanical
      ventilation. All infants were ventilated using volume guarantee plus synchronized
      intermittent positive pressure ventilation (SIPPV + VG mode). Primary outcome was
      the average first PaCO2 in neonates and number of these infants with unacceptable
      first PaCO2. Pre-specified secondary outcomes were the average PaCO2 in infants
      ventilated during the first 48 hrs of ventilation and number of blood gases with
      an unacceptable PaCO2 in the first 48 hours. Sixty two infants were enrolled and
      218 blood gases recorded up to 48 hours of age. RESULTS: The mean PaCO2 on the
      first arterial blood gas for infants ventilated in VG mode from admission to the
      nursery was 39.5 +/- 6.3. The mean PaCO2 in the first 48 hours was 39.37 +/- 6.99
      mmHg. In our study, 91% of all PaCO2 values in the first 48 hours were between 35
      and 60 mmHg. PaCO2 levels were in the acceptable range in 93% of infants at the
      time of first ABG measurement and in 91% of blood gases during the first 48 hours
      of ventilation. CONCLUSION: Newborn infants ventilated with volume guarantee
      ventilation targeting approximately 4 ml/kg of tidal volume, have acceptable
      PaCO2 levels at the first blood gas measurement and during the first 48 hours of
      ventilation.

PMID- 24441092
TI  - Utilization of extracorporeal membrane oxygenation in congenital hypertrophic
      cardiomyopathy caused by maternal diabetes.
AB  - Extracorporeal membrane oxygenation (ECMO) is an advanced strategy utilized in
      many neonatal intensive care units for a specific list of indications. This case
      illustrates a rare but effective use of this therapy for a newborn infant with
      severe hypertrophic cardiomyopathy induced by maternal diabetes. Such infants who
      are unresponsive to conventional therapies may benefit from ECMO support, if it
      is used in conjunction with management strategies that optimize cardiac output. 

PMID- 24441093
TI  - Emergent transcatheter relief of bronchus compression by an ectatic ductus
      arteriosus in a premature neonate: a case report.
AB  - A premature infant with tetralogy of Fallot with pulmonary atresia and prenatal
      compression of the left main bronchus by a large and ectatic patent ductus
      arteriosus is presented. Survival to surgery was accomplished by transcatheter
      placement of a coronary stent into the left mainstem bronchus.

PMID- 24441094
TI  - Neonatal aspiration: not just meconium.
AB  - Aspiration of uncontaminated amniotic fluid as a cause of neonatal respiratory
      distress is scarcely documented. A term neonate who presented with early onset
      respiratory distress with a radiographic appearance of an aspiration syndrome is
      therefore reported. Differential diagnosis and implication of this diagnosis in
      the management of neonatal respiratory distress are discussed. This case
      highlights amniotic fluid aspiration as a possible cause of severe respiratory
      distress even in the absence of meconium stained fluid. 

PMID- 24441095
TI  - Necrotizing enterocolitis after recurrent supraventricular tachycardia.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI)
      emergency that primarily affects premature infants. In the last decade, there
      have been significant advances to our understanding of neonatal NEC. The exact
      etiology of NEC remains unclear, but it is widely considered a multifactorial
      disease; prematurity, enteral feeding, intestinal hypoxia-ischemia, and bacterial
      colonization are considered major risk factors. We report a case of a 35 week
      preterm infant with recurrent episodes of supraventricular tachycardia who
      developed NEC in the second week of life. This case underscores the importance of
      being appropriately cautious in the feeding of these high-risk premature infants.

PMID- 24441096
TI  - Alternative activation of human plasmacytoid DCs in vitro and in melanoma
      lesions: involvement of LAG-3.
AB  - Plasmacytoid dendritic cells (pDCs) at tumor sites are often tolerogenic.
      Although pDCs initiate innate and adaptive immunity upon Toll-like receptor (TLR)
      triggering by pathogens, TLR-independent signals may be responsible for pDC
      activation and immune suppression in the tumor inflammatory environment. To
      identify molecules that are potentially involved in alternative pDC activation,
      we explored the expression and function of lymphocyte activation gene 3 (LAG-3)
      in human pDCs. In this report, we showed the expression of LAG-3 on the cell
      surface of a subset of circulating human pDCs. LAG-3+ pDCs exhibited a partially
      mature phenotype and were enriched at tumor sites in samples from melanoma
      patients. We found that LAG-3 interacted with major histocompatibility complex
      class II (MHC-II) to induce TLR-independent activation of pDCs with limited
      IFNalpha and enhanced IL-6 production. This in vitro cytokine profile of LAG-3
      activated pDCs paralleled that of tumor-associated pDCs analyzed ex vivo. By
      confocal microscopy, LAG-3+ pDCs detected in melanoma-invaded lymph nodes (LNs)
      stained positive for IL-6 and preferentially localized near melanoma cells. These
      results suggest that LAG-3-mediated activation of pDCs takes place in vivo at
      tumor sites, and it is in part responsible for directing an immune-suppressive
      environment. 

PMID- 24441098
TI  - Serum autotaxin levels correlate with pruritus in patients with atopic
      dermatitis.

PMID- 24441097
TI  - Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq
      provides insights into disease mechanisms.
AB  - To increase our understanding of psoriasis, we used high-throughput complementary
      DNA sequencing (RNA-seq) to assay the transcriptomes of lesional psoriatic and
      normal skin. We sequenced polyadenylated RNA-derived complementary DNAs from 92
      psoriatic and 82 normal punch biopsies, generating an average of ~38 million
      single-end 80-bp reads per sample. Comparison of 42 samples examined by both RNA
      seq and microarray revealed marked differences in sensitivity, with transcripts
      identified only by RNA-seq having much lower expression than those also
      identified by microarray. RNA-seq identified many more differentially expressed
      transcripts enriched in immune system processes. Weighted gene coexpression
      network analysis (WGCNA) revealed multiple modules of coordinately expressed
      epidermal differentiation genes, overlapping significantly with genes regulated
      by the long noncoding RNA TINCR, its target gene, staufen-1 (STAU1), the p63
      target gene ZNF750, and its target KLF4. Other coordinately expressed modules
      were enriched for lymphoid and/or myeloid signature transcripts and genes induced
      by IL-17 in keratinocytes. Dermally expressed genes were significantly
      downregulated in psoriatic biopsies, most likely because of expansion of the
      epidermal compartment. These results show the power of WGCNA to elucidate gene
      regulatory circuits in psoriasis, and emphasize the influence of tissue
      architecture in both differential expression and coexpression analysis. 

PMID- 24441100
TI  - Loss of AMPKalpha1 expression is associated with poor survival in melanoma
      patients.

PMID- 24441099
TI  - Localization of serine racemase and its role in the skin.
AB  - D-serine is an endogenous coagonist of the N-methyl-D-aspartate (NMDA)-type
      glutamate receptor in the central nervous system and its synthesis is catalyzed
      by serine racemase (SR). Recently, the NMDA receptor has been found to be
      expressed in keratinocytes (KCs) of the skin and involved in the regulation of KC
      growth and differentiation. However, the localization and role of SR in the skin
      remain unknown. Here, using SR-knockout (SR-KO) mice as the control, we
      demonstrated the localization of the SR protein in the granular and cornified
      layer of the epidermis of wild-type (WT) mice and its appearance in confluent WT
      KCs. We also demonstrated the existence of a mechanism for conversion of L-serine
      to D-serine in epidermal KCs. Furthermore, we found increased expression levels
      of genes involved in the differentiation of epidermal KCs in adult SR-KO mice,
      and alterations in the barrier function and ultrastructure of the epidermis in
      postnatal day 5 SR-KO mice. Our findings suggest that SR in the skin epidermis is
      involved in the differentiation of epidermal KCs and the formation of the skin
      barrier.

PMID- 24441101
TI  - Cytokine effects induced by the human autoallergen alpha-NAC.
AB  - Autoallergy is a phenomenon found in a subgroup of patients with atopic
      dermatitis (AD). These patients exhibit serum IgE reactivity toward autoantigens
      like the alpha-chain of the nascent polypeptide-associated complex (alpha-NAC;
      Hom s 2). alpha-NAC has been shown before to induce T-cell proliferation and
      secretion of IFN-gamma. To elucidate the immune modulating functions alpha-NAC
      may exert, we analyzed its effects on cytokine transcription and secretion in
      peripheral blood mononuclear cells (PBMCs), monocytes, and CD4+ T cells.
      Transcription and secretion of IFN-gamma, IL-17, and IL-22 were increased in
      alpha-NAC-stimulated PBMCs. As IL-17 was significantly upregulated by alpha-NAC,
      we assessed signal transduction in PBMCs and found signal transducer and
      activator of transcription 3 phosphorylation in alpha-NAC-stimulated cells.
      Furthermore, we could show the importance of monocyte activation by alpha-NAC, as
      isolated T cells reacted only weakly toward the stimulation. Inhibition of IL-23
      p19 led to lower amounts of IL-17 in the PBMC supernatants after alpha-NAC
      stimulation. alpha-NAC stimulation of PBMCs from non-allergic donors resulted in
      secretion of IL-10, which was greatly reduced in PBMCs from alpha-NAC-sensitized
      AD patients. Our findings provide insights into the mechanisms of autoallergy,
      investigating the interplay of immune cells, signaling events, and cytokines,
      which are known to be relevant in atopic skin inflammation. 

PMID- 24441102
TI  - SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via
      purinergic receptor activation.
AB  - Serine protease inhibitors of the Kazal-type 9 (SPINK9) is a keratinocyte-derived
      cationic peptide that is found most abundantly in the upper layers of the palmar
      plantar epidermis. In vitro, the peptide displays the capacity to inhibit
      specifically kallikrein-related peptidase 5 (KLK5). Here, we report that cells
      expressing SPINK9 secrete the peptide constitutively. Recombinant SPINK9
      (rSPINK9) provoked transactivation of the EGFR in human keratinocytes, resulting
      in efficient downstream triggering of cell migration. Transactivation occurred
      via functional upregulation of a disintegrin and metalloproteases (ADAMs), as
      evidenced by suppression with a metalloproteinase inhibitor and an EGFR-blocking
      antibody. SPINK9 preparations isolated from human skin also displayed EGFR
      transactivating capacity. The classical purinergic receptor antagonists oxidized
      ATP and pyridoxalphosphate-6-azophenyl-2',4',-disulfonic acid effectively
      suppressed EGFR transactivation by rSPINK9, indicating that in analogy to what
      has recently been reported for the cationic antimicrobial peptides cathelicidin
      LL-37 and bee venom melittin, purinergic receptors have an essential bridging
      role in promoting the upregulation of ADAM function by the cationic peptide.
      SPINK9 could represent an example of how a cationic peptide may subserve multiple
      and interrelated functions that contribute to the maintenance of the physical and
      immunological barrier of the skin. 

PMID- 24441103
TI  - Plakoglobin but not desmoplakin regulates keratinocyte cohesion via modulation of
      p38MAPK signaling.
AB  - Plakoglobin (Pg) and desmoplakin (DP) are adapter proteins within the desmosome,
      providing a mechanical link between desmosomal cadherins as transmembrane
      adhesion molecules and the intermediate filament cytoskeleton. As in the severe
      skin blistering disease pemphigus, autoantibodies against desmosomal adhesion
      molecules induce loss of keratinocyte cohesion at least in part via p38 mitogen
      activated protein kinase (p38MAPK) activation and depletion of desmosomal
      components, we evaluated the roles of Pg and DP in the p38MAPK-dependent loss of
      cell adhesion. Silencing of either Pg or DP reduced cohesion of cultured human
      keratinocytes in dissociation assays. However, Pg but not DP silencing caused
      activation of p38MAPK-dependent keratin filament collapse and cell dissociation.
      Interestingly, extranuclear but not nuclear Pg rescued loss of cell adhesion and
      keratin retraction. In line with this, Pg regulated the levels of the desmosomal
      adhesion molecule desmoglein 3 and tethered p38MAPK to desmosomal complexes. Our
      data demonstrate a role of extranuclear Pg in controlling cell adhesion via
      p38MAPK-dependent regulation of keratin filament organization. 

PMID- 24441104
TI  - The power to detect quantitative trait loci using resequenced, experimentally
      evolved populations of diploid, sexual organisms.
AB  - A novel approach for dissecting complex traits is to experimentally evolve
      laboratory populations under a controlled environment shift, resequence the
      resulting populations, and identify single nucleotide polymorphisms (SNPs) and/or
      genomic regions highly diverged in allele frequency. To better understand the
      power and localization ability of such an evolve and resequence (E&R) approach,
      we carried out forward-in-time population genetics simulations of 1 Mb genomic
      regions under a large combination of experimental conditions, then attempted to
      detect significantly diverged SNPs. Our analysis indicates that the ability to
      detect differentiation between populations is primarily affected by selection
      coefficient, population size, number of replicate populations, and number of
      founding haplotypes. We estimate that E&R studies can detect and localize
      causative sites with 80% success or greater when the number of founder haplotypes
      is over 500, experimental populations are replicated at least 25-fold, population
      size is at least 1,000 diploid individuals, and the selection coefficient on the
      locus of interest is at least 0.1. More achievable experimental designs (less
      replicated, fewer founder haplotypes, smaller effective population size, and
      smaller selection coefficients) can have power of greater than 50% to identify a
      handful of SNPs of which one is likely causative. Similarly, in cases where s >=
      0.2, less demanding experimental designs can yield high power. 

PMID- 24441105
TI  - Bone and fat mass in relation to postnatal levels of insulin-like growth factors
      in prematurely born children at 4 y of age.
AB  - BACKGROUND: Children born prematurely may be at risk of developing osteopenia.
      This study investigated whether insulin-like growth factors (IGFs) in the early
      postnatal period influence bone mass and body composition in prematurely born
      children. METHODS: A total of 74 control (gestational age >36 wk; n = 37) and
      preterm (gestational age <32 wk; n = 37) infants were investigated (mean age +/-
      SD: 4.59 +/- 0.31 y). Bone mineral density, body composition, and markers of bone
      and mineral metabolism were investigated in relation to postnatal IGF levels.
      RESULTS: After adjusting for confounders, we found no differences in bone mass,
      but significantly less lean mass, increased fat mass, and increased osteocalcin
      levels in ex-preterm infants. Forward stepwise multiple analysis revealed that
      higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P
      < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score
      was included in the analysis, higher early postnatal IGF-I levels predicted both
      lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher
      early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at
      4-y follow-up. CONCLUSION: Ex-preterm children have normal bone mass but
      different body composition compared with full-term controls. Higher early IGF-I
      and late postnatal IGF-II concentrations are positive predictors of lumbar spine
      bone mass.

PMID- 24441106
TI  - Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as
      gestation advances.
AB  - BACKGROUND: Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal
      outcome by altering fetal lung and immune system development. We hypothesized
      that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses
      as the lungs develop in utero. METHODS: Fetal lambs were exposed to intra
      amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at
      125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, Toll-like
      receptor (TLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin
      deposition were evaluated. RESULTS: After a single dose of LPS, pulmonary
      inflammatory responses were observed with increases of (i) PU.1 and TLR1 at 125 d
      GA and (ii) monocytes, lymphocytes, TLR2, and TLR6 at 133 d GA. Repetitive LPS
      exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and TLR1 at
      125 d GA; (ii) increases of neutrophils, PU.1, and TLR2 at 133 d GA; and (iii)
      decreases of mast cells, elastin foci, TLR4, and TLR6 at early gestation. At 140
      d GA, only PU.1 was increased after repetitive LPS exposure. CONCLUSION: The
      preterm fetal lung can respond to a single exposure or repeated exposures from
      intra-amniotic LPS in multiple ways, but the absence of inflammatory and
      structural changes in LPS-exposed fetuses delivered near term suggest that the
      fetus can resolve an inflammatory stimulus in utero with time.

PMID- 24441107
TI  - Potential role of WSB1 isoforms in growth and survival of neuroblastoma cells.
AB  - BACKGROUND: WD repeat and SOCS box containing protein 1 (WSB1) generates three
      isoforms that were found to play a role in cancer cell growth and tumor
      progression. We have studied their expression in neuroblastoma (NB). METHODS: The
      behavior of the expression levels of the WSB1 isoforms was analyzed in NB cell
      lines, in an in vivo NB xenograft mouse model, and in primary NB tumors using
      real-time PCR. Effective WSB1 small interfering RNAs were transfected into
      cultured NB cell lines, and cell viability was analyzed using XTT assay and flow
      cytometry. RESULTS: A significant predominance of the WSB1 isoform 3 (WSB1(3))
      expression level was demonstrated in all NB systems examined. Correspondingly,
      combination of WSB1(3) silencing together with WSB1 isoforms 1+2 silencing in NB
      cells showed reduced growth, enhanced apoptosis rate, and increased sensitivity
      to chemotherapeutic agents, specifically related to low expression of WSB1(3).
      CONCLUSION: Our results point to a possible differential role of WSB1 isoforms in
      NB and suggest WSB1(3) as a target for therapy in NB.

PMID- 24441108
TI  - Catalytic asymmetric conjugate addition of terminal alkynes to beta
      trifluoromethyl alpha,beta-enones.
AB  - The first enantioselective conjugate alkynylation of beta-trifluoromethyl
      alpha,beta-enones using terminal alkynes and a taniaphos-Cu(I) complex as
      catalyst is described. Ketones bearing a trifluoromethylated propargylic chiral
      centre in the beta-position were obtained with good yields and high enantiomeric
      excesses (up to 99%). 

PMID- 24441109
TI  - DICOM-based intravascular ultrasound signal intensity analysis: an Echoplaque
      Medical Imaging Bench study.
AB  - BACKGROUND: Most intravascular ultrasound (IVUS) data are stored digitally using
      the Digital Imaging and Communications in Medicine (DICOM) standard. This allows
      random access to studies and improves on the major limitation of conventional
      grayscale IVUS. METHODS: We harvested 129 coronary arteries from 43 autopsied
      cases. Grayscale IVUS and virtual histology-IVUS imaging were performed beginning
      30 mm distal to the ostium of each coronary artery. Grayscale IVUS was processed;
      and the signal intensity was determined from DICOM-stored images using a new
      Medical Imaging Bench system (Echoplaque-MIB). We compared 436 regions of
      interest. The accuracy rate was expressed using the interpolation method and 95%
      confidence interval (CI). RESULTS: Patients' mean age was 49+/-9 years and 82%
      were men. Four patients succumbed to sudden cardiac death and 39 to noncardiac
      death. Grayscale IVUS signal intensity of dense calcium was 215+/-21.1 (95% CI:
      207-223), that of fibrotic plaque was 75+/-17.8 (95% CI: 72-79), and that of
      fibrofatty plaque was 55+/-11.3 (95% CI: 52-59); however, the signal intensity of
      the necrotic core was between fibrotic plaque and dense calcium of 161+/-27.4
      (95% CI: 153-168). Using the interpolation method, the cutoff values were as
      follows: fibrofatty plaque 0-65, fibrotic plaque 66-105, necrotic core 106-187,
      and dense calcium of at least 188. Overall, MIB grayscale had a 78.1% sensitivity
      and a 91.9% specificity versus histopathology. CONCLUSION: Plaque
      characterization using DICOM-based grayscale IVUS signal intensity analysis may
      improve on the major limitation of conventional grayscale IVUS: its inability to
      assess plaque composition.

PMID- 24441110
TI  - Hydrothermal synthesis of copper based nanoparticles: antimicrobial screening and
      interaction with DNA.
AB  - Copper based nanoparticles (Cu-based NPs) of different compositions and sizes
      have been hydrothermally synthesized by varying the reaction time in the presence
      of the biocompatible surfactants polyoxyethylene (20) sorbitan laurate (Tween 20)
      and polyethylene glycol 8000 (PEG 8000). Effective control of the above synthetic
      parameters gave rise to Cu, Cu2O and Cu/Cu2O NPs of 10-44 nm. The antibacterial
      activity of the NPs was screened against Gram-positive (Bacillus subtilis,
      Bacillus cereus, Staphylococcus aureus) and Gram-negative (Xanthomonas
      campestris, Escherichia coli) bacteria. The Cu-based NPs induce pDNA degradation
      in a dose-dependent manner as well as extensive ds CT-DNA degradation. Cu2O NPs
      of 16 nm and 12 nm exhibit the lowest IC50 values (2.13 MUg/mL and 3.7 MUg/mL)
      against B. cereus and B. subtilis, respectively. The agarose gel electrophoresis
      of ds CT-DNA treated with Cu2O NPs demonstrated degradation at high
      concentration. In lower concentrations, viscosity measurements indicated groove
      binding. In regard to the enhanced antibacterial effect and specificity of Cu2O
      NPs against the Gram-positive strains, the activity pathway was further explored
      and ROS production and lipid peroxidation verified. The released copper ions 5.15
      mg/L in distilled water and 16.32 mg/L in nutrient medium, found below the
      critical value to inhibit bacterial growth and thus nanosized composition effect
      is predominant.

PMID- 24441111
TI  - Transitions: From school to adult life.
AB  - Occupational therapy has a unique and valuable contribution to make to the
      transition of students with disabilities from school to productive adult life.
      This contribution includes utilization of an ecological approach that considers
      student performance of essential occupations in a range of natural environments
      including on-the-job. Legislative background, the specific role of occupational
      therapy on the transition team, and challenges related to implementation of
      effective transition services, are presented in this article. 

PMID- 24441112
TI  - Career transitions for persons with severe physical disabilities: integrating
      technological and psychosocial skills and accommodations.
AB  - This article describes a vocational training program entitled, 'Careers in
      Automation for Persons with Severe Physical Disabilities', that was developed by
      the Department of Physical Medicine and Rehabilitation at Tufts University School
      of Medicine in collaboration with the Massachusetts Rehabilitation Commission.
      Its goal is to secure employment for individuals with severe physical impairments
      by using computers and technology as job related accommodations. Psychosocial,
      educational, and vocational profiles are presented for 24 clients over 4 years.
      Three case studies involving persons with traumatic, chronic and developmental
      disabilities illustrate the importance of matching technological accommodations
      with employer needs and personal preferences. Discussion of employment outcomes
      illustrates that the effective use of computers and technology by persons with
      disabilities is best measured not by the degree of sophistication and engineering
      of systems and devices, but by employer and employee satisfaction with job
      performance and productivity. 

PMID- 24441113
TI  - Making career change: transition as a result of cumulative trauma in physical
      therapy.
AB  - Rehabilitation professionals are required in many work situations to lift
      considerable weight. Therapists move patients regularly which may cause a sort of
      cumulative trauma disorder. Realization of performance limitations due to pain,
      may cause emotional responses such as mood changes and loss of concentration as
      well as stimulating the adaptive process. This is a case study of a physical
      therapist's transition from a full case load of neuorlogical patients, parenting
      and homemaking, through considering available alternatives to career decision
      time. 

PMID- 24441114
TI  - Beyond compliance to responsiveness: new measures of quality for accreditation.
AB  - The Accreditation Council, a national accreditation organization since 1969, has
      developed a set of Outcome Based Performance Measures that can be used to assess
      the quality of services and supports for people with disabilities. The
      development of the Outcome Based Performance Measures signals a change in the
      definition of quality from compliance with organizational processes to
      responsiveness to the individual. Based on individual and focus group interviews
      with individuals with disabilities, the new measures of quality indicates the
      outcomes that people expect from services and supports. These generic outcomes
      apply to work and employment settings. The new approach to quality assessment
      treats work and employment as methods or organizational processes which
      facilitate outcomes for people. Work and employment are important for the
      outcomes they facilitate. 

PMID- 24441115
TI  - An integrated program for the prevention and management of musculoskeletal work
      injuries.
AB  - With rising health care costs and a dynamic health care structure in the USA,
      many medical and rehabilitation professionals are seeking cost effective
      strategies to assist employers in preventing and managing musculoskeletal work
      injuries. An integrated approach based on the classic three component model of
      preventive medicine which includes primary, secondary and tertiary prevention is
      discussed. This approach includes ergonomics, medical injury treatment and
      rehabilitation services to provide a comprehensive occupational health program.
      The manner in which these services are packaged for purchase by industry is
      shifting from a fee-for-service system to a capitated program with the provider
      coordinating service delivery at risk. The incentives for successful outcomes are
      tremendous. Challenges in carrying out this program are presented as well as
      discussion of approaches to overcome these barriers. 

PMID- 24441116
TI  - Ergonomic modifications: examining cost and effectiveness.
AB  - This study examined the cost and effectiveness of making ergonomic modifications
      for injured workers at the time of return to work. Factors which were considered
      to be indicative of effective modifications included whether the worker was still
      working at the job for which modifications had been made, the amount of time
      between modification and follow-up call and the employer's rating of the
      effectiveness of the modifications. Thirty-one subjects were all past clients at
      a midwestern rehabilitation facility. Average subject age was 40.9 years; and
      there were 14 males and 17 females. Information relative to the modifications was
      gathered from the subjects' employers through the use of a telephone
      questionnaire. Results indicated an average cost per person of $251.71 and $61.69
      for an average cost per modification, 35% were still working the same job with or
      without restrictions at an average follow-up time of 70.7 weeks. The employers'
      average ratings of the cost effectiveness and effectiveness in keeping the
      employee on the job were 4.3 and 3.8, respectively on a scale of 1-5 (5 being
      very effective). Results suggest that ergonomic modifications can be cost
      effective in keeping the worker on the job. 

PMID- 24441117
TI  - Trends in industrial rehabilitation: ergonomics and cumulative trauma disorders.
AB  - Cumulative trauma disorders are reaching epidemic proportions, affecting almost
      19 million workers per year and costing industry nearly $100 billion annually
      (LaBar, 1991). Increased levels of productivity with fewer job tasks and lighter
      load concentrations on smaller aspects of the body are the primary contributing
      factors to the rise in cumulative trauma disorders (Herbert, 1986). Employers and
      consumers are feeling the significant effects, particularly financial, of
      cumulative trauma disorders and are looking for ways to decrease these disorders
      in the workplace. Ergonomics is a field that is focusing on decreasing work
      injuries and increasing work efficiency. The United States Occupational Safety
      and Health Administration is in the process of developing proposed ergonomic
      guidelines. This paper describes the trends in industrial rehabilitation as they
      relate to cumulative trauma disorder, ergonomics and the components of an
      effective ergonomic program and injury prevention work environment. 

PMID- 24441118
TI  - Work hardening for sub-acute back injured workers: a new approach.
AB  - ACTIDOS (ATD) is a program which takes an innovative approach to work hardening
      based on the needs of acutely back-injured workers. The success lies in the
      coordinated efforts of the interdisciplinary treatment team. ATD integrates the
      return to work process as an aspect of treatment and focuses on functional
      capacity rather than the elimination of pain. The program demonstrates
      encouraging outcome information: 85% of the workers in a specific group returned
      to work within the expected time. 

PMID- 24441119
TI  - Workplace-based occupational rehabilitation in New South Wales, Australia.

PMID- 24441120
TI  - Buyer beware: Educate consumers of continuing education.

PMID- 24441121
TI  - Introduction to the special issue on crystal engineering.

PMID- 24441122
TI  - Crystalline metal-organic frameworks (MOFs): synthesis, structure and function.
AB  - Metal-organic frameworks (MOFs) are a class of hybrid network supramolecular
      solid materials comprised of organized organic linkers and metal cations. They
      can display enormously high surface areas with tunable pore size and
      functionality, and can be used as hosts for a range of guest molecules. Since
      their discovery, MOFs have experienced widespread exploration for their
      applications in gas storage, drug delivery and sensing. This article covers
      general and modern synthetic strategies to prepare MOFs, and discusses their
      structural diversity and properties with respect to application perspectives. 

PMID- 24441123
TI  - Distortions of a flexible metal-organic framework from substituted pendant
      ligands.
AB  - Four new variants of the 1,4-benzenedicarboxylate MIL-53 structure have been
      prepared for Co(II) under solvothermal conditions and their structures solved and
      refined from single-crystal X-ray data. All materials contain pendant pyridine-N
      oxide ligands that bridge pairs of Co(II) atoms in the inorganic backbone of the
      structure via O. By the use of the ligands 3-bromopyridine-N-oxide, 4
      methoxypyridine-N-oxide, isoquinoline-N-oxide and 4-phenylpyridine-N-oxide,
      materials are prepared with the same topology but distinct structures. These
      illustrate how the MIL-53 structure is able to distort to accommodate the bulk of
      the various substituents on the pyridine ring. The bulkiest pendant ligand, 4
      phenylpyridine-N-oxide, results in a distortion of the diamond-shaped channels in
      an opposite sense to that seen previously in expanded forms of the parent MIL-53
      structure. By comparison with published crystal structures for MIL-53 with
      various occluded guests, the structural distortions that take place to
      accommodate the pendant ligands are quantified and it is shown how a twisting of
      the 1,4-benzenedicarboxylate ligand, instead of a hinging about the MU(2)
      carboxylate-metal connection, allows the new structures that are observed. 

PMID- 24441124
TI  - Three new europium(III) methanetriacetate metal-organic frameworks: the influence
      of synthesis on the product topology.
AB  - Three new metal-organic framework structures containing Eu(III) and the little
      explored methanetriacetate (C7H7O6(3-), mta(3-)) ligand have been synthesized.
      Gel synthesis yields a two-dimensional framework with the formula
      [Eu(mta)(H2O)3]n.2nH2O, (I), while two polymorphs of the three-dimensional
      framework material [Eu(mta)(H2O)]n.nH2O, (II) and (III), are obtained through
      hydrothermal synthesis at either 423 or 443 K. Compounds (I) and (II) are
      isomorphous with previously reported Gd(III) compounds, but compound (III)
      constitutes a new phase. Compound (I) can be described in terms of dinuclear
      [Eu2(H2O)4](6+) units bonded through mta(3-) ligands to form a two-dimensional
      framework with topology corresponding to a (6,3)-connected binodal
      (4(3))(4(6)6(6)8(3))-kgd net, where the dinuclear [Eu2(H2O)4](6+) units are
      considered as a single node. Compounds (II) and (III) have distinct three
      dimensional topologies, namely a (4(12)6(3))(4(9)6(6))-nia net for (II) and a
      (4(10)6(5))(4(11)6(4))-K2O2; 36641 net for (III). The crystal density of (III) is
      greater than that of (II), consistent with the increase of temperature, and
      thereby autogeneous pressure, in the hydrothermal synthesis. 

PMID- 24441125
TI  - Metal-organic frameworks based on uranyl and phosphonate ligands.
AB  - Three new crystalline metal-organic frameworks have been prepared from the
      reaction of uranyl nitrate with nitrilotris(methylphosphonic acid) [H6nmp,
      N(CH2PO3H2)3], 1,4-phenylenebis(methylene)diphosphonic acid [H4pmd,
      C6H4(PO3H2)2], and (benzene-1,3,5-triyltris(methylene))triphosphonic acid [H6bmt,
      C6H3(PO3H2)3]. Compound [(UO2)2F(H3nmp)(H2O)].4H2O (I) crystallizes in space
      group C2/c, showing two crystallographically independent uranyl centres with
      pentagonal bipyramidal coordination geometries. While one metal centre is
      composed of a {(UO2)O3(MU-F)}2 dimer, the other comprises an isolated {(UO2)O5}
      polyhedron. Compound [(UO2)(H2pmd)] (II) crystallizes in space group P21/c,
      showing a centrosymmetric uranyl centre with an octahedral {(UO2)O4} coordination
      geometry. Compound [(UO2)3(H3bmt)2(H2O)2].14H2O (III) crystallizes in space group
      P?bar 1, showing two crystallographically independent uranyl centres. One uranyl
      centre is a {(UO2)O5} pentagonal bipyramid similar to that in (I), while the
      other is a {(UO2)O4} centrosymmetric octahedron similar to that in (II).
      Compounds (I) and (III) contain solvent-accessible volumes accounting for ca 23.6
      and 26.9% of their unit-cell volume, respectively. In (I) the cavity has a
      columnar shape and is occupied by disordered water molecules, while in (III) the
      cavity is a two-dimensional layer with more ordered water molecules. All
      compounds have been studied in the solid state using FT-IR spectroscopy.
      Topological studies show that compounds (I) and (III) are trinodal, with 3,6,6-
      and 4,4,6-connected networks, respectively. Compound (II) is instead a 4
      connected uninodal network of the type cds. 

PMID- 24441126
TI  - Organosilver(I) framework assembly with trifluoroacetate and enediyne
      functionalized alicycles.
AB  - Eight new silver(I) trifluoroacetate complexes based on a series of designed
      ligands, each featuring an alicyclic ring with enediyne functionality, have been
      synthesized and characterized by single-crystal X-ray diffraction. Each ethynide
      terminal is inserted into an Agn (n = 4-5) basket, leading to the generation of
      coordination chain or layer structures, but the well shielded ethenyl group does
      not take part in silver-olefin bonding. Variation in ring size of the alicycles
      is shown to influence the construction of the organosilver(I) coordination
      networks, which are consolidated by weak intermolecular interactions in the
      crystal structures. The effect of adding ancillary N-donor ligands to the
      reaction system on the coordination and supramolecular network assembly is also
      investigated. 

PMID- 24441127
TI  - Crystal structure analysis and sublimation thermodynamics of bicyclo derivatives
      of a neuroprotector family.
AB  - The crystal structures of three new structurally related drug-like bicyclo
      derivatives are correlated with measured thermodynamic quantities for their
      sublimation and melting processes. The sublimation thermodynamics are determined
      using the temperature dependencies of the vapour pressure, and the melting
      processes are examined using differential scanning calorimetry. The three
      compounds contain a common N-(3-thia-1-azabicyclo[3.3.1]non-2-ylidene)aniline
      core, with either a CH3, F or CF3 substituent at the 4-position of the aniline
      ring. Lattice energy calculations are made using both the PIXEL and Coulomb
      London-Pauli (CLP) models, and the conformational flexibility of the molecules is
      examined using gas-phase density functional theory (DFT) calculations. The
      experimentally measured crystal lattice energies (DeltaH(0)sub) decrease in the
      order: CH3 > F > CF3. The calculated lattice energies using the PIXEL approach
      are in good agreement with the experimental values, and the partitioned
      intermolecular interaction energies suggest that dispersion contributions
      dominate the crystal structures of all three compounds. The sublimation energies
      and melting points are inversely correlated for the three molecules, with the
      melting points increasing in the order CF3 < F < CH3. 

PMID- 24441128
TI  - Solvates of the antifungal drug griseofulvin: structural, thermochemical and
      conformational analysis.
AB  - Four solvates of an antifungal drug, griseofulvin (GF), were discovered. All the
      solvates were characterized by differential scanning calorimetry,
      thermogravimetric analysis, and their crystal structures were determined by
      single-crystal X-ray diffraction. The solvents that form the solvates are
      acetonitrile, nitromethane and nitroethane (2:1 and 1:1). It was found that all
      the solvates lose the solvent molecules from the crystal lattice between 343 and
      383 K, and that the melting point of the desolvated materials matched the melting
      point of the solvent-free GF (493 K). The conformation of the GF molecule in
      solvent-free form was found to be significantly different from the conformations
      found in the solvates. Solution stability studies revealed that the GF
      acetonitrile solvate transforms to GF and that GF-nitroethane (1:1) solvate
      transforms to GF-nitroethane (2:1) solvate. On the other hand, GF-nitromethane
      and GF-nitroethane (2:1) solvates were found to be stable in solution. Our
      results highlight the importance of the co-crystallization technique in the
      pharmaceutical drug development; it not only expands the solid form diversity but
      also creates new avenues for unraveling novel solvates. 

PMID- 24441129
TI  - Binary co-crystals of the active pharmaceutical ingredient 1,4-bis(4-pyridyl)-2,3
      diaza-1,3-butadiene and camphoric acid.
AB  - Co-crystals comprising the active pharmaceutical ingredient 1,4-bis(4-pyridyl)
      2,3-diaza-1,3-butadiene, C12H10N4, and the chiral co-formers (+)-, (-)- and (rac)
      camphoric acid (cam), C10H16O4, have been synthesized. Two different
      stoichiometries of the API and co-former are obtained, namely 1:1 and 3:2.
      Crystallization experiments suggest that the 3:2 co-crystal is kinetically
      favoured over the 1:1 co-crystal. Single-crystal X-ray diffraction analysis of
      the co-crystals reveals N-H...O hydrogen bonding as the primary driving force for
      crystallization of the supramolecular structures. The 1:1 co-crystal contains
      undulating hydrogen-bonded ribbons, in which the chiral cam molecules impart a
      helical twist. The 3:2 co-crystal contains discrete Z-shaped motifs comprising
      three molecules of the API and two molecules of cam. The 3:2 co-crystals with (+)
      cam, (-)-cam (space group P21) and (rac)-cam (space group P21/n) are
      isostructural. The enantiomeric co-crystals contain pseudo-symmetry consistent
      with space group P21/n, and the co-crystal with (rac)-cam represents a solid
      solution between the co-crystals containing (+)-cam and (-)-cam. 

PMID- 24441130
TI  - Polymorphs, hydrates and solvates of a co-crystal of caffeine with anthranilic
      acid.
AB  - A polymorph screen on a new 1:1 co-crystal of caffeine, C8H10N4O2, with
      anthranilic acid, C7H7NO2, has revealed a rich diversity of crystal forms (two
      polymorphs, two hydrates and seven solvates, including two sets of isostructural
      solvates). These forms were prepared by liquid-assisted grinding and solution
      crystallization, and the crystal structures of nine of these forms have been
      solved using either single-crystal or powder X-ray data. The structures contain O
      H...N and N-H...O hydrogen bonds through which caffeine and anthranilic acid
      molecules assemble to form zigzag-type chains. These chains can interact in an
      anti-parallel and offset manner to form cage- or channel-type skeletons within
      which solvent molecules can be located, giving rise to the diversity of forms
      observed for this co-crystal. In contrast, an equivalent series of liquid
      assisted grinding and solution crystallization experiments with the closely
      related system of theobromine, C7H8N4O2, and anthranilic acid resulted in the
      formation of only one 1:1 co-crystal form. 

PMID- 24441131
TI  - Tuning solubility and stability of hydrochlorothiazide co-crystals.
AB  - Hydrochlorothiazide (HCT), C7H8ClN3O4S2, is a diuretic BCS (Biopharmaceutics
      Classification System) class IV drug which has primary and secondary sulfonamide
      groups. To modify the aqueous solubility of the drug, co-crystals with
      biologically safe co-formers were screened. Multi-component molecular crystals of
      HCT were prepared with nicotinic acid, nicotinamide, succinamide, p-aminobenzoic
      acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals
      were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and
      differential scanning calorimetry. Single crystal structures were obtained for
      four of them. The N-H...O sulfonamide catemer synthons found in the stable
      polymorph of pure HCT are replaced in the co-crystals by drug-co-former
      heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide
      are devoid of the common sulfonamide dimer/catemer synthons. Solubility and
      stability experiments were carried out for the co-crystals in water (neutral pH)
      under ambient conditions. Among the six binary systems, the co-crystal with p
      aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT,
      and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide,
      resorcinol and pyrogallol showed only a 1.5-2-fold increase in solubility and
      transformed to HCT within 1 h of the dissolution experiment. An inverse
      correlation is observed between the melting points of the co-crystals and their
      solubilities. 

PMID- 24441132
TI  - Hydrogen-bond coordination in organic crystal structures: statistics, predictions
      and applications.
AB  - Statistical models to predict the number of hydrogen bonds that might be formed
      by any donor or acceptor atom in a crystal structure have been derived using
      organic structures in the Cambridge Structural Database. This hydrogen-bond
      coordination behaviour has been uniquely defined for more than 70 unique atom
      types, and has led to the development of a methodology to construct hypothetical
      hydrogen-bond arrangements. Comparing the constructed hydrogen-bond arrangements
      with known crystal structures shows promise in the assessment of structural
      stability, and some initial examples of industrially relevant polymorphs, co
      crystals and hydrates are described. 

PMID- 24441133
TI  - Formation of isostructural solid solutions in 2,6-disubstituted N
      phenylformamides and N-phenylthioamides.
AB  - In order to investigate possible isostructural solid solutions of disubstituted N
      phenylformamides and thioamides, we have studied the re-crystallization of pairs
      of compounds selected from 2,6-difluoro-N-phenylformamide (I), 2,6-dichloro-N
      phenylformamide (II), 2,6-dimethyl-N-phenylformamide (III), 2,6-dichloro-N
      phenylthioamide (IV), 2,6-dimethyl-N-phenylthioamide (V), 2,6-diisopropyl-N
      phenylformamide (VI) and 2,6-diisopropyl-N-phenylthioamide (VII). For single
      component 2,6-disubstituted-N-phenylformamides only the trans form occurs in the
      pure crystal, while for thioamides the cis form occurs, with only one exception.
      By forming solid solutions of pairs of these molecules the resulting structures
      all adopt similar N-H...O/S chains in the crystals. Solid solutions (1), (2) and
      (3), resulting from the mixing of (I) and (II), (II) and (III), and (IV) and (V),
      respectively, are all isostructural with each other (space group Pbca). Only co
      crystal (1) is isostructural to both starting materials, while (2) is
      isostructural to only one of the starting pair, (II). Solid solution (3), which
      adopts the same Pbca structure as (1) and (2), is different to the monoclinic
      structures of both the reactants. Solid solution (4) is monoclinic, with similar
      hydrogen-bonded chains, and isostructural to the two components, resulting from
      the composition from the mixing of (VI) and (VII). Isostructural indices were
      used to quantify crystal-packing similarities and differences. Occupancy factors
      of the reactants in each co-crystal differ widely. 

PMID- 24441134
TI  - Towards the chemical control of molecular packing: syntheses and crystal
      structures of three trans-[NiL4(NCS)2] complexes.
AB  - Three nickel(II) isothiocyanato complexes of the formula trans-[NiL4(NCS)2] (L =
      ethylisonicotinate, methylisonicotinate and 4-benzoylpyridine) have been
      prepared: [Ni(ethylisonicotinate)4(NCS)2] (I), [Ni(methylisonicotinate)4(NCS)2]
      (II) and [Ni(4-benzoylpyridine)4(NCS)2] (III). All three complexes are monomeric
      and have a distorted octahedral geometry around Ni(II). Despite their apparent
      molecular similarity, the crystal density of (III) (1.454 g cm(-3)) is
      significantly higher than that of (I) and (II) (both 1.408 g cm(-3)), suggesting
      that the molecular packing is most efficient in (III). A study of the molecular
      Hirshfeld surfaces, together with density functional theory (DFT) calculations,
      provide insights into the origin of the molecular packing features, and it is
      suggested that the greater crystal density of (III) results from smaller
      intermolecular electrostatic repulsions. 

PMID- 24441135
TI  - Solvent-guest control of two extremely similar tetrahydrofuran inclusion
      structures.
AB  - Racemic 2,4,6,8-tetracarbomethoxybicyclo[3.3.0]octa-2,6-diene-3,7-diol, C16H18O10
      (1), was known previously to yield two solvent-free polymorphs and also a
      clathrate inclusion crystal form. Crystallization of (1) yields two inclusion
      compounds containing tetrahydrofuran (THF): (1)4.THF is obtained from a mixture
      of THF and methanol, whereas (1)2.THF is obtained from pure THF. The X-ray
      crystal structures reveal that the two compounds are extremely similar and that
      their host arrangements are essentially identical. They differ, however, in the
      proportion, orientation and host-guest interaction of the included THF molecules.
      The disordered guest molecules in (1)4.THF are oriented along the guest channel
      direction, whereas in (1)2.THF they lie across the channel. This unusual solvent
      guest control of inclusion structures has implications relating to the formation
      of polymorphic structures and other competing crystal forms. 

PMID- 24441136
TI  - Creation of a ternary complex between a crown ether, 4-aminobenzoic acid and 3,5
      dinitrobenzoic acid.
AB  - The creation of ternary multi-component crystals through the introduction of 18
      crown-6 to direct the hydrogen-bonding motifs of the other molecular components
      was investigated for 3,5-dinitrobenzoic acid (3,5-dnba) with 4-aminobenzoic acid
      (4-aba). The creation of a binary complex between 18-crown-6 and 4-aba
      (C12H24O6.2C7H7NO2)2 and a ternary salt between 3,5-dnba, 18-crown-6 and 4-aba
      (C12H24O6.C7H8NO2(+).C7H3N2O6(-).C7H4N2O6) were confirmed by single-crystal
      structure determination. In both structures, the amino molecules bind to the
      crown ether through N-H...O hydrogen bonds, leaving available only a single O
      atom site on the crown with restricted geometry to potentially accept a hydrogen
      bond from 3,5-dnba. While 3,5-dnba and 4-aba form a binary co-crystal containing
      neutral molecules, the shape-selective nature of 18-crown-6 preferentially binds
      protonated amino molecules, thereby leading to the formation of the ternary salt,
      despite the predicted low concentration of the protonated species in the
      crystallizing solution. Thus, through the choice of crown ether it may be
      possible to control both location and nature of the available bonding sites for
      the designed creation of ternary crystals. 

PMID- 24441137
TI  - C-I...NC halogen bonding in two polymorphs of the mixed-valence 2:1 charge
      transfer salt (EDT-TTF-I2)2(TCNQF4), with segregated versus alternated stacks.
AB  - Oxidation of diiodoethylenedithiotetrathiafulvalene (EDT-TTF-I2), C8H4I2S6, with
      the strong oxidizer tetrafluorotetracyanoquinodimethane (TCNQF4), C12F4N4,
      affords, depending on the crystallization solvent, two polymorphs of the 2:1
      charge-transfer salt (EDT-TTF-I2)2(TCNQF4), represented as D2A. In both salts,
      the TCNQF4 is reduced to the radical anion state, and is associated through short
      C-I...NC halogen bonds to two EDT-TTF-I2 molecules. The two polymorphs differ in
      the solid-state association of these trimeric D-A-D motifs. In polymorph (I) the
      trimeric motif is located on an inversion centre, and hence both EDT-TTF-I2
      molecules have +0.5 charge. Together with segregation of the TTF and TCNQ
      derivatives into stacks, this leads to a charge-transfer salt with high
      conductivity. In polymorph (II) two crystallographically independent EDT-TTF-I2
      molecules bear different charges, close to 0 and +1, as deduced from an
      established correlation between intramolecular bond lengths and charge. Overlap
      interactions between the halogen-bonded D(0)-A-?D+? motifs give rise, in a
      perpendicular direction, to diamagnetic A2(2-) and D(0)-D2(2+)-D(0) entities,
      where the radical species are paired into the bonding combination of respectively
      the acceptor LUMOs and donor HOMOs. The strikingly different solid-state
      organization of the halogen-bonded D-A-D motifs provides an illustrative example
      of two modes of face-to-face interaction between pi-type radicals, into either
      delocalized, uniform chains with partial charge transfer and conducting
      behaviour, or localized association of radicals into face-to-face A2(2-) and
      D2(2+) dyads.

PMID- 24441138
TI  - Azobenzene-based difunctional halogen-bond donor: towards the engineering of
      photoresponsive co-crystals.
AB  - Halogen bonding is emerging as a powerful non-covalent interaction in the context
      of supramolecular photoresponsive materials design, particularly due to its high
      directionality. In order to obtain further insight into the solid-state features
      of halogen-bonded photoactive molecules, three halogen-bonded co-crystals
      containing an azobenzene-based difunctional halogen-bond donor molecule, (E)
      bis(4-iodo-2,3,5,6-tetrafluorophenyl)diazene, C12F8I2N2, have been synthesized
      and structurally characterized by single-crystal X-ray diffraction. The crystal
      structure of the non-iodinated homologue (E)-bis(2,3,5,6
      tetrafluorophenyl)diazene, C12H2F8N2, is also reported. It is demonstrated that
      the studied halogen-bond donor molecule is a reliable tecton for assembling
      halogen-bonded co-crystals with potential photoresponsive behaviour. The azo
      group is not involved in any specific intermolecular interactions in any of the
      co-crystals studied, which is an interesting feature in the context of enhanced
      photoisomerization behaviour and photoactive properties of the material systems. 

PMID- 24441139
TI  - Competition between hydrogen and halogen bonding in the structures of 5,10
      dihydroxy-5,10-dihydroboranthrenes.
AB  - X-ray crystallographic and computational studies are reported for a series of
      boranthrenes, substituted with halogen atoms. The role of competitive hydrogen (O
      H...O, O-H...F, C-H...O) and halogen (Cl...Cl, O...Br, F...F) bonding
      interactions on the molecular arrangement in the crystal structures is discussed.
      The structural analysis and calculations reveal that the O-H...O hydrogen bond in
      the unsubstituted derivative 5,10-dihydroxy-5,10-dihydroboranthrene, C12H10B2O2,
      is of moderate strength (ca -20 kJ mol(-1)), but weaker than that in the related
      thiophene derivative 4,8-dihydro-4,8-dihydroxy-p-diborino[2,3-b:5,6
      b]dithiophene, C8H6B2O2S2 (ca -40 kJ mol(-1)). This is due to shielding of the OH
      group by the H atoms in the beta-position of the boranthrene unit. Structural
      diversity derived from the flexibility of the O-H...O hydrogen bond facilitates
      the occurrence of other competitive interactions. For instance, in the 1,6
      difluoro derivative, C12H8B2F2O2, the crystal packing results from O-H...F and
      F...F interactions. In turn, the 1,6-dibromo derivative, C12H8B2Br2O2, is
      dominated by Br...O halogen-bond interactions. In the most interesting case, the
      1,6-dichloro derivative, C12H8B2Cl2O2, molecular disorder leads to the formation
      of two different supramolecular arrangements co-existing in the crystal lattice,
      one based on the Cl...Cl and C-H...O bonds, and the other stabilized by O-H...O
      hydrogen bonds. Calculations performed with density-functional theory (DFT;
      CRYSTAL09) and PIXEL methodologies show that both lattices are characterized by
      similar energy values (ca -100 kJ mol(-1)). A mixed arrangement with random or
      short-range-ordered molecular orientations can also be expected. 

PMID- 24441140
TI  - A top-down approach to crystal engineering of a racemic Delta2-isoxazoline.
AB  - The crystal structure of racemic dimethyl (4RS,5RS)-3-(4-nitrophenyl)-4,5
      dihydroisoxazole-4,5-dicarboxylate, C13H12N2O7, has been determined by single
      crystal X-ray diffraction. By analysing the degree of growth of the
      morphologically important crystal faces, a ranking of the most relevant non
      covalent interactions determining the crystal structure can be inferred. The
      morphological information is considered with an approach opposite to the
      conventional one: instead of searching inside the structure for the potential key
      interactions and using them to calculate the crystal habit, the observed crystal
      morphology is used to define the preferential lines of growth of the crystal, and
      then this information is interpreted by means of density functional theory (DFT)
      calculations. Comparison with the X-ray structure confirms the validity of the
      strategy, thus suggesting this top-down approach to be a useful tool for crystal
      engineering. 

PMID- 24441141
TI  - Spin-coupling in dimers of 2,3-dicyano-5,6-dichlorosemiquinone radical anions in
      the crystalline state.
AB  - A crystal engineering approach is used to stabilize a radical anion in the
      crystalline state and to modulate the separation distance within pi-stacks of
      anion radicals. Alkali metal salts of 2,3-dicyano-5,6-dichlorosemiquinone
      (C8Cl2N2O2, DDQ?- radical anions were prepared and their crystal structures
      determined: LiDDQ.2H2O.(CH3)2CO, RbDDQ.2H2O and CsDDQ.2H2O. In these structures,
      stacked dimers of radical anions are formed within pi-stacked columns. Within the
      stacked dimers, interplanar separation distances are significantly shorter than
      the sum of the van der Waals radii for two C atoms; the shortest is 2.812 A for
      the Li salt and the longest is 2.925 A for the Cs salt. Diamagnetic character,
      observed by electron paramagnetic resonance spectroscopy, indicates spin-coupling
      of the unpaired electrons within the radical anion dimer. The electron-rich cyano
      substituents on DDQ?- influence the electron redistribution within the ring
      skeleton. The crystalline compounds are also characterized by IR spectroscopy,
      complemented by quantum-chemical calculations based on both isolated and periodic
      models.

PMID- 24441143
TI  - System level dynamics of post-translational modifications.
AB  - Attempts to characterize cellular behaviors with static, univariate measurements
      cannot fully capture biological complexity and lead to an inadequate
      interpretation of cellular processes. Significant biological insight can be
      gleaned by considering the contribution of dynamic protein post-translational
      modifications (PTMs) utilizing systems-level quantitative analysis. High
      resolution mass spectrometry coupled with computational modeling of dynamic
      signal-response relationships is a powerful tool to reveal PTM-mediated
      regulatory networks. Recent advances using this approach have defined network
      kinetics of growth factor signaling pathways, identified systems level responses
      to cytotoxic perturbations, elucidated kinase-substrate relationships, and
      unraveled the dynamics of PTM cross-talk. Innovations in multiplex measurement
      capacity, PTM annotation accuracy, and computational integration of datasets
      promise enhanced resolution of dynamic PTM networks and further insight into
      biological intricacies. 

PMID- 24441144
TI  - Photocatalytic application of nanosized CdS immobilized onto functionalized
      MWCNTs.
AB  - Nanosized semiconductor CdS immobilized onto modified multi-walled carbon
      nanotubes (MWCNTs) carrying poly(amidoamine) dendron units were visualized by HR
      TEM. Evidently, spherical CdS nanoparticles 3-5 nm in diameter were identified.
      Moreover, EDX spectroscopy gave additional spectroscopic proof of the presence of
      CdS in the CdS-MWCNTs hybrid material. The photocatalytic activity of CdS-MWCNTs
      toward the decomposition of rhodamine B (RhB) was examined by monitoring spectral
      changes in the characteristic absorption band of RhB centred at 554 nm. The
      latter absorption band of RhB was found to continuously depress during visible
      light irradiation in the presence of CdS-MWCNTs, with faster kinetic rates as
      compared with the case when only reference CdS was present. The current result
      was rationalized in terms of efficient photoinduced electron-transfer from CdS to
      MWCNTs within the intrahybrid CdS-MWCNTs. In this frame, the suggested mechanism
      for the high and fast photocatalytic decomposition of RhB supports the
      accumulation of electrons in MWCNTs, which then react with molecular oxygen, thus
      reducing it to superoxide radical anion O2(-) responsible for the generation of
      the highly reactive species of HO and HOO. The latter together with the holes
      generated in photoexcited CdS were responsible for the decomposition of RhB.
      Finally, the photocatalyst CdS-MWCNTs was recovered and efficiently reused for
      four consecutive catalytic cycles, thus highlighting its wider applicability in
      removing organic pollutants from water. 

PMID- 24441145
TI  - Combination peptide immunotherapy suppresses antibody and helper T-cell responses
      to the RhD protein in HLA-transgenic mice.
AB  - The offspring from pregnancies of women who have developed anti-D blood group
      antibodies are at risk of hemolytic disease of the newborn. We have previously
      mapped four peptides containing immunodominant T-helper cell epitopes from the
      RhD protein and the purpose of the work was to develop these into a product for
      suppression of established anti-D responses. A panel of each of the four
      immunodominant RhD peptides was synthesized with modifications to improve
      manufacturability and solubility, and screened for retention of recognition by
      human T-helper cells. A selected version of each sequence was combined in a
      mixture (RhDPmix), which was tested for suppressive ability in a humanized murine
      model of established immune responses to RhD protein. After HLA-DR15 transgenic
      mice had been immunized with RhD protein, a single dose of RhDPmix, given either
      intranasally (P=0.008, Mann-Whitney rank sum test) or subcutaneously (P=0.043),
      rapidly and significantly suppressed the ongoing antibody response. This was
      accompanied by reduced T-helper cell responsiveness, although this change was
      less marked for subcutaneous RhDPmix delivery, and by the recruitment of cells
      with a regulatory T-cell phenotype. The results support human trials of RhDPmix
      peptide immunotherapy in women with established antibody responses to the RhD
      blood group. 

PMID- 24441147
TI  - Post-thrombotic syndrome is an independent determinant of health-related quality
      of life following both first proximal and distal deep vein thrombosis.

PMID- 24441146
TI  - t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an
      international study of 62 patients.
AB  - Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the
      2008 World Health Organization classification, but little is known about the
      clinical implications of t(6;9)-positive myeloid leukemia in children. This
      international multicenter study presents the clinical and genetic characteristics
      of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54
      diagnosed as having acute myeloid leukemia, representing <1% of all childhood
      acute myeloid leukemia, and eight as having myelodysplastic syndrome. The
      t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4
      years), male predominance (sex ratio 1.7), French-American-British M2
      classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was
      substantially better than previously reported with a 5-year event-free survival
      of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of
      relapse of 57%. Hematopoietic stem cell transplantation in first complete
      remission improved the 5-year event-free survival compared with chemotherapy
      alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%;
      P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year
      overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene
      expression profiling showed a unique signature characterized by significantly
      higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion,
      t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a
      high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression
      signature. 

PMID- 24441148
TI  - Serum hepcidin following autologous hematopoietic cell transplantation: an
      illustration of the interplay of iron status, erythropoiesis and inflammation.

PMID- 24441149
TI  - Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as
      a putative oncogene in acute myeloid leukemia with 14q32 aberrations.
AB  - Acute myeloid leukemia is a neoplasm characterized by recurrent molecular
      aberrations traditionally demonstrated by cytogenetic analyses. We used high
      density genome-wide genotyping and gene expression profiling to reveal acquired
      cryptic abnormalities in acute myeloid leukemia. By genome-wide genotyping of 137
      cases of primary acute myeloid leukemia, we disclosed a recurrent focal
      amplification on chromosome 14q32, which included the genes BCL11B, CCNK,
      C14orf177 and SETD3, in two cases. In the affected cases, the BCL11B gene showed
      consistently high mRNA expression, whereas the expression of the other genes was
      unperturbed. Fluorescence in situ hybridization on 40 cases of acute myeloid
      leukemia with high BCL11B mRNA expression [2.5-fold above median; 40 out of 530
      cases (7.5%)] revealed 14q32 abnormalities in two additional cases. In the four
      BCL11B-rearranged cases the 14q32 locus was fused to different partner
      chromosomes. In fact, in two cases, we demonstrated that the focal 14q32
      amplifications were integrated into transcriptionally active loci. The
      translocations involving BCL11B result in increased expression of full-length
      BCL11B protein. The BCL11B-rearranged acute myeloid leukemias expressed both
      myeloid and T-cell markers. These biphenotypic acute leukemias all carried FLT3
      internal tandem duplications, a characteristic marker of acute myeloid leukemia.
      BCL11B mRNA expression in acute myeloid leukemia appeared to be strongly
      associated with expression of other T-cell-specific genes. Myeloid 32D(GCSF-R)
      cells ectopically expressing Bcl11b showed decreased proliferation rate and less
      maturation. In conclusion, by an integrated approach involving high-throughput
      genome-wide genotyping and gene expression profiling we identified BCL11B as a
      candidate oncogene in acute myeloid leukemia. 

PMID- 24441150
TI  - Recovery of clinical but not radiographic outcomes by the delayed addition of
      adalimumab to methotrexate-treated Japanese patients with early rheumatoid
      arthritis: 52-week results of the HOPEFUL-1 trial.
AB  - OBJECTIVE: The aim of this study was to compare efficacy outcomes of initial
      treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX
      monotherapy in Japanese early RA patients naive to MTX with high disease
      activity. METHODS: Patients completing the 26-week, randomized, placebo
      controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open
      label adalimumab + MTX. Patients were assessed for mean change from baseline in
      the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and
      for the proportions of patients achieving clinical, functional or radiographic
      remission. RESULTS: Of 333 patients assessed, 278 (137 from the initial
      adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52
      week study. Significant differences in clinical and functional parameters
      observed during the 26-week blinded period were not apparent following the
      addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed
      radiographic progression through week 52 in both groups, but patients who
      received adalimumab + MTX throughout the study exhibited less radiographic
      progression than those who received placebo + MTX during the first 26 weeks (mean
      DeltamTSS at week 52 = 2.56 vs 3.30, P < 0.001). CONCLUSION: Delayed addition of
      adalimumab in Japanese MTX-naive early RA patients did not impact clinical and
      functional outcomes at week 52 compared with the earlier addition of adalimumab.
      However, the accrual of significant structural damage during blinded placebo +
      MTX therapy contributed to the persistence of differences between the treatment
      strategies, suggesting that Japanese patients at risk for aggressive disease
      should benefit from the early inclusion of adalimumab + MTX combination therapy.
      Trial registration. ClinicalTrials.gov (http://clinicaltrials.gov/), NCT00870467.

PMID- 24441151
TI  - The effect of tocilizumab on bone mineral density in patients with methotrexate
      resistant active rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to analyse the effects of therapy with
      tocilizumab (TCZ), an anti-IL-6 receptor antibody, on BMD of the lumbar spine and
      femoral neck in patients with RA. METHODS: Eighty-six patients with active RA
      (indicated by a 28-joint DAS ESR >3.2) despite treatment with MTX 12 mg/week were
      included in this open-label prospective study and started on TCZ (8 mg/kg every 4
      weeks). All patients used a stable dosage of MTX and were not allowed to use
      steroids or bisphosphonates during the study period. BMD of the lumbar spine and
      femoral neck was measured by dual-energy X-ray absorptiometry at baseline and 52
      weeks after initiating TCZ. RESULTS: Seventy-eight patients completed this study.
      BMD of the lumbar spine and femoral neck remained stable after 1 year of TCZ
      treatment. In 33 patients who had osteopenia at baseline, there was a significant
      increase in BMD of the lumbar spine [mean 0.022 (s.d.) 0.042, P < 0.05] and
      femoral neck [0.024 (0.0245), P < 0.05]. CONCLUSION: TCZ affects BMD in patients
      who had active RA despite treatment with MTX. BMD of the lumbar spine and femoral
      neck in patients with normal BMD at baseline was stable. TCZ increased the BMD of
      patients who had osteopenia at baseline.

PMID- 24441152
TI  - Vasculitis associated with rheumatoid arthritis: a case-control study.
AB  - OBJECTIVE: The aim of this study was to determine the clinical correlates and
      predictors of rheumatoid vasculitis (RV). METHODS: A retrospective cohort of
      patients with RV evaluated at a tertiary referral centre between 1 January 2000
      and 1 January 2010 was identified. RV cases were compared in a 1:2 ratio to
      controls (RA without vasculitis) to identify risk factors for developing RV.
      RESULTS: Eighty-six RV cases (58% women, 88% white) were identified.
      Histopathological confirmation was available for 58% of patients. Cutaneous
      vasculitis was the most common presentation, followed by vasculitic neuropathy.
      The median age at presentation was 63 years and the median duration of RA was
      10.8 years. One third were current smokers. The majority were seropositive and
      had elevated inflammatory markers. Treatment was with a range of immunomodulating
      agents. At 6 months, 38% of patients achieved complete remission, 52% had partial
      improvement and 10% noted no clinical improvement. Thirty-six per cent relapsed
      by 5 years and 26% died. After adjusting for age and disease duration, current
      smoking at RA diagnosis [odds ratio (OR) 1.98], coexistent peripheral vascular
      disease (OR 3.98), cerebrovascular disease (OR 6.48), severe RA (OR 2.02)
      (characterized by radiographic erosions, nodulosis on clinical examination or
      requirement of joint surgery) and the use of biologics (OR 2.80) were found to
      increase the odds for developing RV; the use of HCQ (OR 0.54, CI 0.31, 0.94) and
      low-dose aspirin (OR 0.42, CI 0.21, 0.85) was associated with decreased odds for
      developing RV. CONCLUSION: This largest single-centre series of patients with RV
      suggests that even in recent years, RV remains a serious complication of RA and
      is associated with significant mortality.

PMID- 24441154
TI  - Aquatic hyphomycete species are screened by the hyporheic zone of woodland
      streams.
AB  - Aquatic hyphomycetes strongly contribute to organic matter dynamics in streams,
      but their abilities to colonize leaf litter buried in streambed sediments remain
      unexplored. Here, we conducted field and laboratory experiments (slow-filtration
      columns and stream-simulating microcosms) to test the following hypotheses: (i)
      that the hyporheic habitat acting as a physical sieve for spores filters out
      unsuccessful strategists from a potential species pool, (ii) that decreased pore
      size in sediments reduces species dispersal efficiency in the interstitial water,
      and (iii) that the physicochemical conditions prevailing in the hyporheic habitat
      will influence fungal community structure. Our field study showed that spore
      abundance and species diversity were consistently reduced in the interstitial
      water compared with surface water within three differing streams. Significant
      differences occurred among aquatic hyphomycetes, with dispersal efficiency of
      filiform-spore species being much higher than those with compact or
      branched/tetraradiate spores. This pattern was remarkably consistent with those
      found in laboratory experiments that tested the influence of sediment pore size
      on spore dispersal in microcosms. Furthermore, leaves inoculated in a stream and
      incubated in slow-filtration columns exhibited a fungal assemblage dominated by
      only two species, while five species were codominant on leaves from the stream
      simulating microcosms. Results of this study highlight that the hyporheic zone
      exerts two types of selection pressure on the aquatic hyphomycete community, a
      physiological stress and a physical screening of the benthic spore pool, both
      leading to drastic changes in the structure of fungal community. 

PMID- 24441153
TI  - Effects of tofacitinib on lymphocytes in rheumatoid arthritis: relation to
      efficacy and infectious adverse events.
AB  - OBJECTIVES: To assess the effects of tofacitinib on T lymphocytes in RA patients
      with a special focus on efficacy and infectious adverse events (iAEs). METHODS:
      Forty-four RA patients participated in 12-month phase II/III randomized clinical
      trials and an open-label extension trial. Peripheral lymphocyte subsets and in
      vitro CD4(+) T lymphocyte proliferation were measured in 23 patients of 44 at
      baseline and at the end of the 12-month trial. RESULTS: Forty-four patients [35
      females, age 54.3 years, disease duration 84.3 months, simplified disease
      activity index (SDAI) 36.5, CRP 24.9 mg/l, ESR 53 mm/h, MMP-3 284 pg/ml, RF 172.6
      IU/ml, neutrophil count 4842 per MUl, lymphocyte count 1410 per MUl] were treated
      with tofacitinib. At the end of the study, the SDAI improved to 6.2, but the
      peripheral lymphocyte count and absolute numbers of CD4(+) and CD8(+)
      subpopulations did not change during this period. However, CD4(+) T lymphocyte
      proliferation was suppressed, which correlated with the improvement in SDAI, but
      not with iAEs (n = 19) during the 12-month treatment. Receiver operating
      characteristic analysis identified a CD8(+) T lymphocyte count <= 211 per MUl at
      baseline as a significant predictor of clinically significant iAEs. CONCLUSION:
      The efficacy of tofacitinib is mediated through the suppression of CD4(+) T
      lymphocyte proliferation without affecting the absolute number of these cells in
      the periphery. A low CD8(+) T cell count at baseline correlated with the
      development of iAEs during the treatment of RA patients.

PMID- 24441155
TI  - Bacterial cellulose as a substrate for microbial cell culture.
AB  - Bacterial cellulose (BC) has a range of structural and physicochemical properties
      that make it a particularly useful material for the culture of bacteria. We
      studied the growth of 14 genera of bacteria on BC substrates produced by
      Acetobacter xylinum and compared the results to growth on the commercially
      available biopolymers agar, gellan, and xanthan. We demonstrate that BC produces
      rates of bacterial cell growth that typically exceed those on the commercial
      biopolymers and yields cultures with higher titers of cells at stationary phase.
      The morphology of the cells did not change during growth on BC. The rates of
      nutrient diffusion in BC being higher than those in other biopolymers is likely a
      primary factor that leads to higher growth rates. Collectively, our results
      suggest that the use of BC may open new avenues in microbiology by facilitating
      bacterial cell culture and isolation. 

PMID- 24441156
TI  - Cold air plasma to decontaminate inanimate surfaces of the hospital environment.
AB  - The hospital environment harbors bacteria that may cause health care-associated
      infections. Microorganisms, such as multiresistant bacteria, can spread around
      the patient's inanimate environment. Some recently introduced biodecontamination
      approaches in hospitals have significant limitations due to the toxic nature of
      the gases and the length of time required for aeration. This study evaluated the
      in vitro use of cold air plasma as an efficient alternative to traditional
      methods of biodecontamination of hospital surfaces. Cultures of methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE),
      extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli, and
      Acinetobacter baumannii were applied to different materials similar to those
      found in the hospital environment. Artificially contaminated sections of
      marmoleum, mattress, polypropylene, powder-coated mild steel, and stainless steel
      were then exposed to a cold air pressure plasma single jet for 30 s, 60 s, and 90
      s, operating at approximately 25 W and 12 liters/min flow rate. Direct plasma
      exposure successfully reduced the bacterial load by log 3 for MRSA, log 2.7 for
      VRE, log 2 for ESBL-producing E. coli, and log 1.7 for A. baumannii. The present
      report confirms the efficient antibacterial activity of a cold air plasma single
      jet plume on nosocomial bacterially contaminated surfaces over a short period of
      time and highlights its potential for routine biodecontamination in the clinical
      environment. 

PMID- 24441157
TI  - Genes conferring copper resistance in Sinorhizobium meliloti CCNWSX0020 also
      promote the growth of Medicago lupulina in copper-contaminated soil.
AB  - Sinorhizobium meliloti CCNWSX0020, isolated from root nodules of Medicago
      lupulina growing in gold mine tailings in the northwest of China, displayed both
      copper resistance and growth promotion of leguminous plants in copper
      contaminated soil. Nevertheless, the genetic and biochemical mechanisms
      responsible for copper resistance in S. meliloti CCNWSX0020 remained
      uncharacterized. To investigate genes involved in copper resistance, an S.
      meliloti CCNWSX0020 Tn5 insertion library of 14,000 mutants was created. Five
      copper-sensitive mutants, named SXa-1, SXa-2, SXc-1, SXc-2, and SXn, were
      isolated, and the disrupted regions involved were identified by inverse PCR and
      subsequent sequencing. Both SXa-1 and SXa-2 carried a transposon insertion in
      lpxXL (SM0020_18047), encoding the LpxXL C-28 acyltransferase; SXc-1 and SXc-2
      carried a transposon insertion in merR (SM0020_29390), encoding the regulatory
      activator; SXn contained a transposon insertion in omp (SM0020_18792), encoding a
      hypothetical outer membrane protein. The results of reverse transcriptase PCR (RT
      PCR) combined with transposon gene disruptions revealed that SM0020_05862,
      encoding an unusual P-type ATPase, was regulated by the MerR protein. Analysis of
      the genome sequence showed that this P-type ATPase did not contain an N-terminal
      metal-binding domain or a CPC motif but rather TPCP compared with CopA from
      Escherichia coli. Pot experiments were carried out to determine whether growth
      and copper accumulation of the host plant M. lupulina were affected in the
      presence of the wild type or the different mutants. Soil samples were subjected
      to three levels of copper contamination, namely, the uncontaminated control and
      47.36 and 142.08 mg/kg, and three replicates were conducted for each treatment.
      The results showed that the wild-type S. meliloti CCNWSX0020 enabled the host
      plant to grow better and accumulate copper ions. The plant dry weight and copper
      content of M. lupulina inoculated with the 5 copper-sensitive mutants
      significantly decreased in the presence of CuSO4. 

PMID- 24441158
TI  - Molecular characterization of an NADPH-dependent acetoin reductase/2,3-butanediol
      dehydrogenase from Clostridium beijerinckii NCIMB 8052.
AB  - Acetoin reductase is an important enzyme for the fermentative production of 2,3
      butanediol, a chemical compound with a very broad industrial use. Here, we report
      on the discovery and characterization of an acetoin reductase from Clostridium
      beijerinckii NCIMB 8052. An in silico screen of the C. beijerinckii genome
      revealed eight potential acetoin reductases. One of them (CBEI_1464) showed
      substantial acetoin reductase activity after expression in Escherichia coli. The
      purified enzyme (C. beijerinckii acetoin reductase [Cb-ACR]) was found to exist
      predominantly as a homodimer. In addition to acetoin (or 2,3-butanediol), other
      secondary alcohols and corresponding ketones were converted as well, provided
      that another electronegative group was attached to the adjacent C-3 carbon.
      Optimal activity was at pH 6.5 (reduction) and 9.5 (oxidation) and around 68
      degrees C. Cb-ACR accepts both NADH and NADPH as electron donors; however, unlike
      closely related enzymes, NADPH is preferred (Km, 32 MUM). Cb-ACR was compared to
      characterized close homologs, all belonging to the "threonine dehydrogenase and
      related Zn-dependent dehydrogenases" (COG1063). Metal analysis confirmed the
      presence of 2 Zn(2+) atoms. To gain insight into the substrate and cofactor
      specificity, a structural model was constructed. The catalytic zinc atom is
      likely coordinated by Cys37, His70, and Glu71, while the structural zinc site is
      probably composed of Cys100, Cys103, Cys106, and Cys114. Residues determining
      NADP specificity were predicted as well. The physiological role of Cb-ACR in C.
      beijerinckii is discussed. 

PMID- 24441159
TI  - Occurrence of diarrheagenic virulence genes and genetic diversity in Escherichia
      coli isolates from fecal material of various avian hosts in British Columbia,
      Canada.
AB  - Contamination of surface water by fecal microorganisms originating from human and
      nonhuman sources is a public health concern. In the present study, Escherichia
      coli isolates (n = 412) from the feces of various avian host sources were
      screened for various virulence genes: stx1 and stx2 (Shiga toxin-producing E.
      coli [STEC]), eae (enteropathogenic E. coli [EPEC]), est-h, est-p, and elt
      (encoding heat-stable toxin [ST] variants STh and STp and heat-labile toxin [LT],
      respectively) (enterotoxigenic E. coli [ETEC]), and ipaH (enteroinvasive E. coli
      [EIEC]). None of the isolates were found to be positive for stx1, while 23% (n =
      93) were positive for only stx2, representing STEC, and 15% (n = 63) were
      positive for only eae, representing EPEC. In addition, five strains obtained from
      pheasant were positive for both stx2 and eae and were confirmed as non-O157 by
      using an E. coli O157 rfb (rfbO157) TaqMan assay. Isolates positive for the
      virulence genes associated with ETEC and EIEC were not detected in any of the
      hosts. The repetitive element palindromic PCR (rep-PCR) fingerprint analysis
      identified 143 unique fingerprints, with an overall Shannon diversity index of
      2.36. Multivariate analysis of variance (MANOVA) showed that the majority of the
      STEC and EPEC isolates were genotypically distinct from nonpathogenic E. coli and
      clustered independently. MANOVA analysis also revealed spatial variation among
      the E. coli isolates, since the majority of the isolates clustered according to
      the sampling locations. Although the presence of virulence genes alone cannot be
      used to determine the pathogenicity of strains, results from this study show that
      potentially pathogenic STEC and EPEC strains can be found in some of the avian
      hosts studied and may contaminate surface water and potentially impact human
      health. 

PMID- 24441160
TI  - Duplex PCR methods for the molecular detection of Escherichia fergusonii isolates
      from broiler chickens.
AB  - Escherichia fergusonii is an emerging pathogen that has been isolated from a wide
      range of infections in animals and humans. Primers targeting specific genes,
      including yliE (encoding a conserved hypothetical protein of the cellulose
      synthase and regulator of cellulose synthase island), EFER_1569 (encoding a
      hypothetical protein, putative transcriptional activator for multiple antibiotic
      resistance), and EFER_3126 (encoding a putative triphosphoribosyl-dephospho
      coenzyme A [CoA]), were designed for the detection of E. fergusonii by
      conventional and real-time PCR methods. Primers were screened by in silico PCR
      against 489 bacterial genomic sequences and by both PCR methods on 55 reference
      and field strains. Both methods were specific and sensitive for E. fergusonii,
      showing amplification only for this bacterium. Conventional PCR required a
      minimum bacterial concentration of approximately 10(2) CFU/ml, while real-time
      PCR required a minimum of 0.3 pg of DNA for consistent detection. Standard curves
      showed an efficiency of 98.5%, with an R(2) value of 0.99 for the real-time PCR
      assay. Cecal and cloacal contents from 580 chickens were sampled from broiler
      farms located in the Fraser Valley (British Columbia, Canada). Presumptive E.
      fergusonii isolates were recovered by enrichment and plating on differential and
      selective media. Of 301 total presumptive isolates, 140 (46.5%) were identified
      as E. fergusonii by biochemical profiling with the API 20E system and 268 (89.0%)
      using PCR methods. E. fergusonii detection directly from cecal and cloacal
      samples without preenrichment was achieved with both PCR methods. Hence, the PCR
      methods developed in this work significantly improve the detection of E.
      fergusonii. 

PMID- 24441162
TI  - The global response regulator ExpA controls virulence gene expression through
      RsmA-mediated and RsmA-independent pathways in Pectobacterium wasabiae SCC3193.
AB  - ExpA (GacA) is a global response regulator that controls the expression of major
      virulence genes, such as those encoding plant cell wall-degrading enzymes
      (PCWDEs) in the model soft rot phytopathogen Pectobacterium wasabiae SCC3193.
      Several studies with pectobacteria as well as related phytopathogenic
      gammaproteobacteria, such as Dickeya and Pseudomonas, suggest that the control of
      virulence by ExpA and its homologues is executed partly by modulating the
      activity of RsmA, an RNA-binding posttranscriptional regulator. To elucidate the
      extent of the overlap between the ExpA and RsmA regulons in P. wasabiae, we
      characterized both regulons by microarray analysis. To do this, we compared the
      transcriptomes of the wild-type strain, an expA mutant, an rsmA mutant, and an
      expA rsmA double mutant. The microarray data for selected virulence-related genes
      were confirmed through quantitative reverse transcription (qRT-PCR).
      Subsequently, assays were performed to link the observed transcriptome
      differences to changes in bacterial phenotypes such as growth, motility, PCWDE
      production, and virulence in planta. An extensive overlap between the ExpA and
      RsmA regulons was observed, suggesting that a substantial portion of ExpA
      regulation appears to be mediated through RsmA. However, a number of genes
      involved in the electron transport chain and oligogalacturonide metabolism, among
      other processes, were identified as being regulated by ExpA independently of
      RsmA. These results suggest that ExpA may only partially impact fitness and
      virulence via RsmA. 

PMID- 24441161
TI  - A rice gene for microbial symbiosis, Oryza sativa CCaMK, reduces CH4 flux in a
      paddy field with low nitrogen input.
AB  - Plants have mutualistic symbiotic relationships with rhizobia and fungi by the
      common symbiosis pathway, of which Ca(2+)/calmodulin-dependent protein kinase
      (encoded by CCaMK) is a central component. Although Oryza sativa CCaMK (OsCCaMK)
      is required for fungal accommodation in rice roots, little is known about the
      role of OsCCaMK in rice symbiosis with bacteria. Here, we report the effect of a
      Tos17-induced OsCCaMK mutant (NE1115) on CH4 flux in low-nitrogen (LN) and
      standard-nitrogen (SN) paddy fields compared with wild-type (WT) Nipponbare. The
      growth of NE1115 was significantly decreased compared with that of the WT,
      especially in the LN field. The CH4 flux of NE1115 in the LN field was
      significantly greater (156 to 407% in 2011 and 170 to 816% in 2012) than that of
      the WT, although no difference was observed in the SN field. The copy number of
      pmoA (encodes methane monooxygenase in methanotrophs) was significantly higher in
      the roots and rhizosphere soil of the WT than in those of NE1115. However, the
      mcrA (encodes methyl coenzyme M reductase in methanogens) copy number did not
      differ between the WT and NE1115. These results were supported by a (13)C-labeled
      CH4-feeding experiment. In addition, the natural abundance of (15)N in WT shoots
      (3.050/00) was significantly lower than in NE1115 shoots (3.450/00), suggesting
      greater N2 fixation in the WT because of dilution with atmospheric N2 (0.000/00).
      Thus, CH4 oxidation and N2 fixation were simultaneously activated in the root
      zone of WT rice in the LN field and both processes are likely controlled by
      OsCCaMK. 

PMID- 24441163
TI  - Hot-alkaline DNA extraction method for deep-subseafloor archaeal communities.
AB  - A prerequisite for DNA-based microbial community analysis is even and effective
      cell disruption for DNA extraction. With a commonly used DNA extraction kit,
      roughly two-thirds of subseafloor sediment microbial cells remain intact on
      average (i.e., the cells are not disrupted), indicating that microbial community
      analyses may be biased at the DNA extraction step, prior to subsequent molecular
      analyses. To address this issue, we standardized a new DNA extraction method
      using alkaline treatment and heating. Upon treatment with 1 M NaOH at 98 degrees
      C for 20 min, over 98% of microbial cells in subseafloor sediment samples
      collected at different depths were disrupted. However, DNA integrity tests showed
      that such strong alkaline and heat treatment also cleaved DNA molecules into
      short fragments that could not be amplified by PCR. Subsequently, we optimized
      the alkaline and temperature conditions to minimize DNA fragmentation and retain
      high cell disruption efficiency. The best conditions produced a cell disruption
      rate of 50 to 80% in subseafloor sediment samples from various depths and
      retained sufficient DNA integrity for amplification of the complete 16S rRNA gene
      (i.e., ~1,500 bp). The optimized method also yielded higher DNA concentrations in
      all samples tested compared with extractions using a conventional kit-based
      approach. Comparative molecular analysis using real-time PCR and pyrosequencing
      of bacterial and archaeal 16S rRNA genes showed that the new method produced an
      increase in archaeal DNA and its diversity, suggesting that it provides better
      analytical coverage of subseafloor microbial communities than conventional
      methods. 

PMID- 24441164
TI  - Temporal alterations in the secretome of the selective ligninolytic fungus
      Ceriporiopsis subvermispora during growth on aspen wood reveal this organism's
      strategy for degrading lignocellulose.
AB  - The white-rot basidiomycetes efficiently degrade all wood cell wall polymers.
      Generally, these fungi simultaneously degrade cellulose and lignin, but certain
      organisms, such as Ceriporiopsis subvermispora, selectively remove lignin in
      advance of cellulose degradation. However, relatively little is known about the
      mechanism of selective ligninolysis. To address this issue, C. subvermispora was
      grown in liquid medium containing ball-milled aspen, and nano-liquid
      chromatography-tandem mass spectrometry was used to identify and estimate
      extracellular protein abundance over time. Several manganese peroxidases and an
      aryl alcohol oxidase, both associated with lignin degradation, were identified
      after 3 days of incubation. A glycoside hydrolase (GH) family 51
      arabinofuranosidase was also identified after 3 days but then successively
      decreased in later samples. Several enzymes related to cellulose and xylan
      degradation, such as GH10 endoxylanase, GH5_5 endoglucanase, and GH7
      cellobiohydrolase, were detected after 5 days. Peptides corresponding to
      potential cellulose-degrading enzymes GH12, GH45, lytic polysaccharide
      monooxygenase, and cellobiose dehydrogenase were most abundant after 7 days. This
      sequential production of enzymes provides a mechanism consistent with selective
      ligninolysis by C. subvermispora. 

PMID- 24441165
TI  - Identification of genetic bases of vibrio fluvialis species-specific biochemical
      pathways and potential virulence factors by comparative genomic analysis.
AB  - Vibrio fluvialis is an important food-borne pathogen that causes diarrheal
      illness and sometimes extraintestinal infections in humans. In this study, we
      sequenced the genome of a clinical V. fluvialis strain and determined its
      phylogenetic relationships with other Vibrio species by comparative genomic
      analysis. We found that the closest relationship was between V. fluvialis and V.
      furnissii, followed by those with V. cholerae and V. mimicus. Moreover, based on
      genome comparisons and gene complementation experiments, we revealed genetic
      mechanisms of the biochemical tests that differentiate V. fluvialis from closely
      related species. Importantly, we identified a variety of genes encoding potential
      virulence factors, including multiple hemolysins, transcriptional regulators, and
      environmental survival and adaptation apparatuses, and the type VI secretion
      system, which is indicative of complex regulatory pathways modulating
      pathogenesis in this organism. The availability of V. fluvialis genome sequences
      may promote our understanding of pathogenic mechanisms for this emerging
      pathogen. 

PMID- 24441166
TI  - Taxonomic identification of commensal bacteria associated with the mucosa and
      digesta throughout the gastrointestinal tracts of preweaned calves.
AB  - Bacterial colonization in the gastrointestinal tracts (GIT) of preweaned calves
      is very important, since it can influence early development and postweaning
      performance and health. This study investigated the composition of the bacteria
      along the GIT (rumen, jejunum, ileum, cecum, and colon) of preweaned bull calves
      (3 weeks old) using pyrosequencing to understand the segregation of bacteria
      between the mucosal surface and digesta. Phylogenetic analysis revealed that a
      total of 83 genera belonging to 13 phyla were distributed throughout the GIT of
      preweaned calves, with the Firmicutes, Bacteroidetes, and Proteobacteria
      predominating. Quantitative PCR (qPCR) analysis of selected abundant bacterial
      genera (Prevotella, Bacteroides, Lactobacillus, and Faecalibacterium) revealed
      that their prevalence was significantly different among the GIT regions and
      between mucosa- and digesta-associated communities. Rumens contained the most
      diverse bacterial population, consisting of 47 genera, including 16 rumen
      specific genera, followed by the large intestine and then the small intestine.
      Bacterial species richness was higher at the mucosal surface than in the local
      digesta, with the exception of the rumen. The majority of bacteria found on the
      rumen epithelial surface and within the small intestine could not be identified
      due to a lack of known genus-level information. Thus, future studies will be
      required to fully characterize the microbiome during the development of the
      rumens and the mucosal immune systems of newborn calves. This is the first study
      to analyze in depth the bacterial composition of the GIT microbiome in preweaned
      calves, which extends previous findings regarding early rumen colonization and
      bacterial segregation between mucosa- and digesta-associated microbial
      communities. 

PMID- 24441168
TI  - An interactive simulated electronic health record using Google Drive.

PMID- 24441167
TI  - Animal rennets as sources of dairy lactic acid bacteria.
AB  - The microbial composition of artisan and industrial animal rennet pastes was
      studied by using both culture-dependent and -independent approaches.
      Pyrosequencing targeting the 16S rRNA gene allowed to identify 361 operational
      taxonomic units (OTUs) to the genus/species level. Among lactic acid bacteria
      (LAB), Streptococcus thermophilus and some lactobacilli, mainly Lactobacillus
      crispatus and Lactobacillus reuteri, were the most abundant species, with
      differences among the samples. Twelve groups of microorganisms were targeted by
      viable plate counts revealing a dominance of mesophilic cocci. All rennets were
      able to acidify ultrahigh-temperature-processed (UHT) milk as shown by pH and
      total titratable acidity (TTA). Presumptive LAB isolated at the highest dilutions
      of acidified milks were phenotypically characterized, grouped, differentiated at
      the strain level by randomly amplified polymorphic DNA (RAPD)-PCR analysis, and
      subjected to 16S rRNA gene sequencing. Only 18 strains were clearly identified at
      the species level, as Enterococcus casseliflavus, Enterococcus faecium,
      Enterococcus faecalis, Enterococcus lactis, Lactobacillus delbrueckii, and
      Streptococcus thermophilus, while the other strains, all belonging to the genus
      Enterococcus, could not be allotted into any previously described species. The
      phylogenetic analysis showed that these strains might represent different unknown
      species. All strains were evaluated for their dairy technological performances.
      All isolates produced diacetyl, and 10 of them produced a rapid pH drop in milk,
      but only 3 isolates were also autolytic. This work showed that animal rennet
      pastes can be sources of LAB, mainly enterococci, that might contribute to the
      microbial diversity associated with dairy productions. 

PMID- 24441169
TI  - Blue button movement: engaging ourselves and patients.

PMID- 24441171
TI  - A new paradigm for transcription factor TFIIB functionality.
AB  - Experimental and bioinformatic studies of transcription initiation by RNA
      polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation
      less uniform across gene promoters than initially thought. However, the general
      transcription factor TFIIB is presumed to be universally required for RNAP2
      transcription initiation. Based on bioinformatic analysis of data and effects of
      TFIIB knockdown in primary and transformed cell lines on cellular functionality
      and global gene expression, we report that TFIIB is dispensable for transcription
      of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene
      transcription and replication. We report a novel cell cycle TFIIB regulation and
      localization of the acetylated TFIIB variant on the transcriptionally silent
      mitotic chromatids. Taken together, these results establish a new paradigm for
      TFIIB functionality in human gene expression, which when downregulated has potent
      anti-viral effects. 

PMID- 24441172
TI  - Modest familial risks for multiple sclerosis: a registry-based study of the
      population of Sweden.
AB  - Data on familial recurrence rates of complex diseases such as multiple sclerosis
      give important hints to aetiological factors such as the importance of genes and
      environment. By linking national registries, we sought to avoid common
      limitations of clinic-based studies such as low numbers, poor representation of
      the population and selection bias. Through the Swedish Multiple Sclerosis
      Registry and a nationwide hospital registry, a total of 28 396 patients with
      multiple sclerosis were identified. We used the national Multi-Generation
      Registry to identify first and second degree relatives as well as cousins, and
      the Swedish Twin Registry to identify twins of patients with multiple sclerosis.
      Crude and age corrected familial risks were estimated for cases and found to be
      in the same range as previously published figures. Matched population-based
      controls were used to calculate relative risks, revealing lower estimates of
      familial multiple sclerosis risks than previously reported, with a sibling
      recurrence risk (lambdas = 7.1; 95% confidence interval: 6.42-7.86).
      Surprisingly, despite a well-established lower prevalence of multiple sclerosis
      amongst males, the relative risks were equal among maternal and paternal
      relations. A previously reported increased risk in maternal relations could thus
      not be replicated. An observed higher transmission rate from fathers to sons
      compared with mothers to sons suggested a higher transmission to offspring from
      the less prevalent sex; therefore, presence of the so-called 'Carter effect'
      could not be excluded. We estimated the heritability of multiple sclerosis using
      74 757 twin pairs with known zygosity, of which 315 were affected with multiple
      sclerosis, and added information from 2.5 million sibling pairs to increase
      power. The heritability was estimated to be 0.64 (0.36-0.76), whereas the shared
      environmental component was estimated to be 0.01 (0.00-0.18). In summary, whereas
      multiple sclerosis is to a great extent an inherited trait, the familial relative
      risks may be lower than usually reported. 

PMID- 24441173
TI  - Does cognitive functioning predict chronic pain? Results from a prospective
      surgical cohort.
AB  - It is well established that chronic pain impairs cognition, particularly memory,
      attention and mental flexibility. Overlaps have been found between the brain
      regions involved in pain modulation and cognition, including in particular the
      prefrontal cortex and the anterior cingulate cortex, which are involved in
      executive function, attention and memory. However, whether cognitive function may
      predict chronic pain has not been investigated. We addressed this question in
      surgical patients, because such patients can be followed prospectively and may
      have no pain before surgery. In this prospective longitudinal study, we
      investigated the links between executive function, visual memory and attention,
      as assessed by clinical measurements and the development of chronic pain, its
      severity and neuropathic symptoms (based on the 'Douleur Neuropathique 4'
      questionnaire), 6 and 12 months after surgery (total knee arthroplasty for
      osteoarthritis or breast surgery for cancer). Neuropsychological tests included
      the Trail-Making Test A and B, and the Rey-Osterrieth Complex Figure copy and
      immediate recall, which assess cognitive flexibility, visuospatial processing and
      visual memory. Anxiety, depression and coping strategies were also evaluated. In
      total, we investigated 189 patients before surgery: 96% were re-evaluated at 6
      months, and 88% at 12 months. Multivariate logistic regression (stepwise
      selection) for the total group of patients indicated that the presence of
      clinical meaningful pain at 6 and 12 months (pain intensity >= 3/10) was
      predicted by poorer cognitive performance in the Trail Making Test B (P = 0.0009
      and 0.02 for pain at 6 and 12 months, respectively), Rey-Osterrieth Complex
      Figure copy (P = 0.015 and 0.006 for pain at 6 and 12 months, respectively) and
      recall (P = 0.016 for pain at 12 months), independently of affective variables.
      Linear regression analyses indicated that impaired scores on these tests
      predicted pain intensity (P < 0.01) and neuropathic symptoms in patients with
      pain (P < 0.05), although the strength of the association was less robust for
      neuropathic symptoms. These results were not affected by the type of surgery or
      presurgical pain, similar findings being obtained specifically for patients who
      initially had no pain. In conclusion, these findings support, for the first time,
      the notion that premorbid limited cognitive flexibility and memory capacities may
      be linked to the mechanisms of pain chronicity and probably also to its
      neuropathic quality. This may imply that patients with deficits in executive
      functioning or memory because of cerebral conditions have a greater risk of pain
      chronicity after a painful event. 

PMID- 24441174
TI  - The key features of percutaneous coronary intervention with chronic total
      obstruction lesion of right coronary artery.
AB  - We summarize recent research on percutaneous coronary intervention of chronic
      total occlusion of the right coronary artery. We then explain the method and
      technology of forward and backward revascularization in chronic total occlusion
      of the right coronary artery. Finally, we emphasize the monitoring methods and
      key treating measures for better prognosis of the patients. 

PMID- 24441175
TI  - Antioxidants and tumor necrosis factor alpha-inhibiting activity of sesame oil
      against doxorubicin-induced cardiotoxicity.
AB  - OBJECTIVE: Oxidative stress is currently considered to be the key factor in
      doxorubicin-induced cardiotoxicity. Comparatively small quantity of the
      endogenous antioxidant content of the heart is assumed to be the predisposing
      factor for doxorubicin-induced cardiotoxicity. The present research was designed
      to evaluate the antioxidant potential and tumor necrosis factor alpha-(TNF-alpha)
      inhibiting activity of sesame oil against acute doxorubicin-induced
      cardiotoxicity. METHODS: Male Wistar albino rats (180-200 g) were administered
      sesame oil in two dissimilar doses (5 and 10 ml/kg body weight, orally) for 30
      days, followed by a single dose of doxorubicin (30 mg/kg s.c.). RESULTS: In the
      doxorubicin-treated group, increased oxidative stress was proven by a significant
      rise of thiobarbituric acid reactive substances level and a decrease of
      myocardial superoxide dismutase, catalase and reduced glutathione content.
      Histopathological studies showed myocardial necrosis with accumulation of
      inflammatory cells, vacuolization and overall enlargement of the myocardium.
      Western blot analysis showed marked expression of TNF-alpha in the myocardium.
      Alteration in biochemical parameters by doxorubicin administration was prevented
      significantly (p < 0.0001) in the 5 and 10 ml/kg sesame oil treated rat hearts.
      Treatment with 5 and 10 ml/kg of sesame oil reduced the doxorubicin-induced TNF
      alpha expression in the myocardium, which was associated with reduced myocyte
      injury. The overall effect of sesame oil was comparable with probucol, which
      shows similar protection. CONCLUSION: The chronic oral administration of sesame
      oil prevents acute doxorubicin-induced cardiotoxicity by enhancing cardiac
      endogenous antioxidants and decreasing myocardial TNF-alpha expression.

PMID- 24441176
TI  - Different effects of a novel CaO-MgO-SiO2-based multiphase glass-ceramic on cell
      behaviors of normal and cancer cells in vitro.
AB  - The effects in vitro of a novel multiphase glass-ceramic (with nominal
      composition of 43.19% CaO, 7.68% MgO, and 49.13% SiO2 in weight percent) on cell
      adhesion, proliferation, differentiation and ultrastructure of human osteosarcoma
      cell line MG63, mouse fibroblasts L929, and human lung adenocarcinoma epithelial
      cell line A549 were investigated in this research. Scanning electron microscopy
      (SEM) micrographs revealed that the surface morphology of this glass-ceramic was
      beneficial to cell adhesion. The glass-ceramic extracts at certain concentrations
      could stimulate the proliferation and differentiation of MG63 and L929 cells,
      whereas inhibit A549 proliferation, which might be resulted from the released Si
      ions. In addition, when cultured with 0.1mg/mL glass-ceramic powder suspension,
      the cell ultrastructure of MG63 showed abundant organelles and L929 displayed the
      phenomena of cellular stress response. While more interestingly, A549 exhibited
      chromatin condensation, mitochondria swell and RER expansion, which was presumed
      to be early signs of apoptosis. These results suggest that this novel CaO-MgO
      SiO2-based multiphase glass-ceramic has potential for bone regeneration and
      tissue engineering applications. 

PMID- 24441177
TI  - Formulation of Newcastle disease virus coupled calcium phosphate nanoparticles:
      an effective strategy for oculonasal delivery to chicken.
AB  - In this report, calcium phosphate (CaP) nanoparticles were synthesized by
      continuous flow method using beta-cyclodextrin (beta-CD) as a medium and
      functionalized with amino propyl triethoxy silane (APTES). The blood
      biocompatibility of the nanoparticles was assessed using the whole blood
      haemolysis, erythrocytes haemolysis and erythrocyte aggregation tests. Based on
      the results, we found that the synthesized beta-CD-CaP nanoparticles did not
      cause any remarkable toxic effect. The 5-dimethylthiazol-2-yl-2, 5
      diphenyltetrazolium bromide (MTT) assay of chicken peripheral blood mononucleated
      cells (PBMCs) incubated with these nanoparticles indicated that these particles
      did not exert any significant cytotoxicity. The aminosilane functional group
      modified beta-CD-CaP was used as tool for coupling of Newcastle disease virus
      (NDV). The NDV conjugated nanoparticles were confirmed by using Fourier
      transformed infrared spectroscopy, X-ray diffraction patterns, Raman spectroscopy
      differential scanning calorimetry and energy-dispersive X-ray spectroscopy.
      Immunogenicity trials in chickens proved that beta-CD-CaP-NDV used as a vaccine
      was better than the commercial vaccine when given oculonasally during the first 2
      weeks post vaccination. The birds vaccinated with the above nano-NDV vaccine were
      completely protected against virulent NDV challenge. This study confirms that the
      oculonasal beta-CD-CaP-NDV delivery of vaccines is a potential method for
      enhancing the immune responses of existing commercial vaccines. 

PMID- 24441178
TI  - Temperature-triggered tumor-specific delivery of anticancer agents by cRGD
      conjugated thermosensitive liposomes.
AB  - One of the most effective methods to treat cancer is the specific delivery of
      anticancer drugs to the target site. To achieve this goal, we designed an
      anticancer drug with mild hyperthermia-mediated triggering and tumor-specific
      delivery. To enhance the thermosensitive drug release, we incorporated elastin
      like polypeptide (ELP), which is known to be a thermally responsive phase
      transition peptide into the dipalmitoylphosphatidylcholine (DPPC)-based liposome
      surface. Additionally, cyclic arginine-glycine-aspartic acid (cRGD) binds to
      alphavbeta3 integrin, which is overexpressed in angiogenic vasculature and tumor
      cells, was introduced on the liposome. ELP-modified liposomes with the cRGD
      targeting moiety were prepared using a lipid film hydration method, and
      doxorubicin (DOX) was loaded into the liposome by the ammonium sulfate-gradient
      method. The cRGD-targeted and ELP-modified DOX-encapsulated liposomes (RELs)
      formed spherical vesicles with a mean diameter of 181 nm. The RELs showed 75% and
      83% DOX release at 42 degrees C and 45 degrees C, respectively. The stability of
      RELs was maintained up to 12h without the loss of their thermosensitive function
      for drug release. Flow cytometry results showed that the cellular uptake of DOX
      in RELs into alphavbeta3 integrin-overexpressing U87MG and HUVEC cells was 8-fold
      and 10-fold higher, respectively, than that of non-targeting liposomes. Confocal
      microscopy revealed that REL released DOX only under the mild hyperthermia
      condition at 42 degrees C by showing the localization of DOX in nuclei and the
      liposomes in the cytosol. The cell cytotoxicity results demonstrated that REL can
      efficiently kill U87MG cells through cRGD targeting and thermal triggering. The
      in vivo tumoral accumulation measurement showed that the tumor-targeting effect
      of RELs was 5-fold higher than that of non-targeting liposomes. This stable,
      target-specific, and thermosensitive liposome shows promise to enhance
      therapeutic efficacy if it is applied along with a relevant external heat
      generating medical system.

PMID- 24441179
TI  - Surfactin restores and enhances swarming motility under heavy metal stress.
AB  - The present work reports the importance of lipopeptide biosurfactant on swarming
      motility of multi-metal resistant (MMR) bacterium under heavy metal stress. The
      MMR bacteria strain CM100B, identified as Bacillus cereus, was isolated from the
      coal mine sample. The strain was able to grow and reduce several metals namely
      Cd(2+), Co(2+), Cu(2+), Ni(2+), Mn(2+) and Pb(2+) ions which are common
      environmental pollutants. Presence of toxic heavy metal ions in the swarming
      medium significantly altered the motility of CM100B. Presence of Cd(2+) and
      Pb(2+) ions inhibited development of peritrichous flagella, thus inhibiting
      swarming motility. However, the addition of anionic biosurfactant surfactin
      restored (in case of Cd(2+) and Pb(2+) ions) or enhanced (in case of Co(2+),
      Cu(2+), Ni(2+) and Mn(2+)) the swarming ability of CM100B. Zeta potential studies
      for determining bacterial cell surface charge indicated that surfactin provided a
      suitable swarming environment to bacteria even under metal stress by chelating to
      cationic metal ions. Non-ionic surfactant Triton X-100 was unable to restore
      swarming under Cd(2+) and Pb(2+) ion stress. Thus, suggesting that surfactin can
      aid in motility not only by reducing the surface tension of swarming medium but
      also by binding to metal ions in the presence of metal ions stress. 

PMID- 24441180
TI  - Magnetic pH-responsive nanocarrier with long spacer length and high colloidal
      stability for controlled delivery of doxorubicin.
AB  - A novel magnetic nanocarrier with long spacer length and high colloidal stability
      has been prepared for effective delivery of doxorubicin (DOX). First,
      poly(amidoamine) (PAMAM) dendrimer was grown up onto the surface of
      superparamagnetic iron oxide nanoparticles to increase the loading amount of
      amine groups. Then, terminal amine groups were functionalized by polyethylene
      glycol dimethylester to increase the spacer length. Then anticancer drug DOX was
      covalently attached onto the system by hydrazone bond to forms a pH-sensitive
      nanocarrier. This system is designed to combine the advantage of magnetic
      targeting, high drug loading capacity, and controlled release. 

PMID- 24441181
TI  - One-step fabrication of agent-loaded biodegradable microspheroids for drug
      delivery and imaging applications.
AB  - Non-spherical particles may offer advantages over conventional spherical systems
      for drug delivery applications. This work describes the fabrication of agent
      loaded poly(lactic-co-glycolic acid) (PLGA) spheroids via the emulsion solvent
      evaporation (ESE) method. The versatility of this technique for loading a variety
      of therapeutics is demonstrated via loading of paclitaxel, bovine serum albumin,
      and cadmium sulfide nanoparticles into PLGA spheroids. The encapsulation
      efficiency for spheroids fabricated via oil-in-water (O/W) emulsions is highest
      at low aqueous phase surfactant concentrations while the encapsulation efficiency
      for spheroids made via water-in-oil-in-water (W/O/W) is highest at high aqueous
      phase surfactant concentrations and basic aqueous phase pH values. Particle
      aspect ratio polydispersity can be minimized via the use of high aqueous phase
      PVA concentration and pH. The ESE technique is an attractive alternative to
      recently described methods for fabrication of non-spherical particles due to its
      simplicity in setup, high particle yield and adaptability to a variety of
      biodegradable polymers and therapeutics. 

PMID- 24441182
TI  - Mesoporous bioactive glass doped-poly (3-hydroxybutyrate-co-3-hydroxyhexanoate)
      composite scaffolds with 3-dimensionally hierarchical pore networks for bone
      regeneration.
AB  - Scaffolds play a critical role in bone tissue engineering. Composite scaffolds
      made of biodegradable polymers and bioactive inorganic compounds have
      demonstrated superior properties in bone defect repair. In this study, highly
      bioactive, resorbable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)
      based scaffolds were prepared using combinational 3-dimensional (3D) printing and
      surface-doping protocol. Structural and morphological characterization of the
      composite scaffolds demonstrated the homogenous surface-coating of mesoporous
      bioactive glass (MBG) throughout their porous framework. These hierarchical
      scaffolds showed bioactivity superior to that of scaffolds made of pure PHBHHx.
      MBG coating appeared to provide a better environment for human mesenchymal stem
      cells (hMSCs) attachment, activity, and osteogenic differentiation. Our study
      indicates that MBG-coated PHBHHx (PHBM) scaffolds may be excellent candidates for
      use in bone tissue engineering.

PMID- 24441183
TI  - KiSS1 inhibits growth and invasion of osteosarcoma cells through inhibition of
      the MAPK pathway.
AB  - As a metastasis suppressor, KiSS1 has been implicated in numerous human cancers.
      However, recent studies have demonstrated that KiSS1 promotes tumor growth and
      metastasis in breast cancer, and it is unclear about the expression and function
      of KiSS1 in human osteosarcoma (OS). The aim of the present study was to
      investigate the role and molecular mechanisms of KiSS1 in human OS. The
      expression of KiSS1 was assessed by immunohistochemical assay using a tissue
      microarray procedure in forty cases of OS tissues. A gain-of-function approach
      was used to observe the effects of lentiviral vector-mediated overexpression of
      KiSS1 (Lv-KiSS1) on the biological behaviors including proliferative activities
      and invasive potential of OS MG-63 cells, indicated by MTT and Transwell assays,
      respectively. The results showed that the expression of KiSS1 protein in OS
      tissues was significantly lowered compared to that in adjacent non-cancerous
      tissues (ANCT) (42.5% vs 70.0%, P=0.023), and had negative correlation with
      distant metastases of the tumor (P=0.019). Overexpression of KiSS1 inhibited
      proliferation and invasion of OS cells with the decreased expression of p38 MAPK
      and matrix metalloproteinase-9 (MMP-9). Taken together, our findings indicate
      that the decreased expression of KiSS1 is correlated with distant metastasis of
      OS, and KiSS1 may function as a tumor suppressor in OS cells through inhibition
      of the MAPK pathway, suggesting that KiSS1 may serve as a potential therapeutic
      target for the treatment of cancer. 

PMID- 24441184
TI  - Three-dimensional scaffold-free fusion culture: the way to enhance chondrogenesis
      of in vitro propagated human articular chondrocytes.
AB  - Cartilage regeneration based on isolated and culture-expanded chondrocytes has
      been studied in various in vitro models, but the quality varies with respect to
      the morphology and the physiology of the synthesized tissues. The aim of our
      study was to promote in vitro chondrogenesis of human articular chondrocytes
      using a novel three-dimensional (3-D) cultivation system in combination with the
      chondrogenic differentiation factors transforming growth factor beta 2 (TGF-b2)
      and L-ascorbic acid. Articular chondrocytes isolated from six elderly patients
      were expanded in monolayer culture. A single-cell suspension of the
      dedifferentiated chondrocytes was then added to agar-coated dishes without using
      any scaffold material, in the presence, or absence of TGF-b2 and/or L-ascorbic
      acid. Three-dimensional cartilage-like constructs, called single spheroids, and
      microtissues consisting of several spheroids fused together, named as fusions,
      were formed. Generated tissues were mainly characterized using histological and
      immunohistochemical techniques. The morphology of the in vitro tissues shared
      some similarities to native hyaline cartilage in regard to differentiated S100
      positive chondrocytes within a cartilaginous matrix, with strong collagen type II
      expression and increased synthesis of proteoglycans. Finally, our innovative
      scaffold-free fusion culture technique supported enhanced chondrogenesis of human
      articular chondrocytes in vitro. These 3-D hyaline cartilage-like microtissues
      will be useful for in vitro studies of cartilage differentiation and
      regeneration, enabling optimization of functional tissue engineering and possibly
      contributing to the development of new approaches to treat traumatic cartilage
      defects or osteoarthritis. 

PMID- 24441185
TI  - Dentin matrix protein 1 and dentin sialophosphoprotein in human sound and carious
      teeth: an immunohistochemical and colorimetric assay.
AB  - Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) are
      extracellular matrix proteins produced by odontoblasts involved in the dentin
      mineralization. The aim this study was to compare the distribution of DMP1 and
      DSPP in human sound dentin vs human sclerotic dentin. Sixteen sound and sixteen
      carious human molars were selected, fixed in paraformaldehyde and processed for
      immunohistochemical detection of DMP1 and DSPP by means of light microscopy,
      transmission electron microscopy (TEM) and high-resolution field emission in-lens
      scanning electron microscopy (FEI-SEM). Specimens were submitted to a pre
      embedding or a post-embedding immunolabeling technique using primary antibodies
      anti DMP1 and anti-DSPP and gold-conjugated secondary antibodies. Other samples
      were processed for the detection of DMP1 and DSPP levels. Dentin from these
      samples was mechanically fractured to powder, then a protein extraction and a
      protein level detection assay were performed. DMP1 and DSPP were more abundant in
      carious than in sound samples. Immunohistochemical analyses in sclerotic dentin
      disclosed a high expression of DMP1 and DSPP inside the tubules, suggesting an
      active biomineralization of dentin by odontoblasts. Furthermore, the detection of
      small amounts of these proteins inside the tubules far from the carious lesion,
      as shown in the present study, is consistent with the hypothesis of a preventive
      defense of all dentin after a noxious stimulus has undermined the tooth. 

PMID- 24441186
TI  - Merkel cell distribution in the human eyelid.
AB  - Although Merkel cell carcinoma of the eye lid is reported frequently in the
      literature, only limited information exists about the distribution of Merkel
      cells in this tissue. Therefore, serial sections of 18 human cadaver eye lids
      (donors ages ranging between 63 and 97 years) were stained for cytokeratin 20 in
      various planes. The overall appearance of Merkel cells in these samples was low
      and mainly located in the outer root layer of the cilia hair follicles. Merkel
      cells were more frequent in the middle, and almost not detectable at the nasal
      and temporal edges. The localization is in accordance with that of Merkel cell
      carcinoma, but concerning the scarce appearance within this adulthood group, a
      specific physiological role of these cells in the eye lid is difficult to
      establish. 

PMID- 24441188
TI  - Correlation between PARP-1 immunoreactivity and cytomorphological features of
      parthanatos, a specific cellular death in breast cancer cells.
AB  - In parthanatos, a PARP-1 (poly (ADP-ribose) polymerase 1)-mediated cell death,
      dissipation of mitochondrial membrane potential, large-scale DNA fragmentation
      and chromatin condensation were observed. In contrast to apoptosis, it does not
      cause apoptotic bodies formation. Although PARP-1-mediated cell death presents
      loss of membrane integrity similar to necrosis, it does not induce cell swelling.
      The purpose of the study was to correlate the immunohistochemical parameters of
      PARP-1 reactivity and the selected cytomorphological features of parthanatos: the
      lack of apoptotic bodies and the absence of necrosis in breast cancer (BC)
      specimens. Immunohistochemistry for PARP-1 was performed on 83 BC specimens.
      Correlations between parameters of PARP-1 expression and sub-cellular
      localisation and the presence of apoptotic bodies and necrosis were evaluated.
      High expression of PARP-1 (ImmunoReactive Score >=6) was associated with the lack
      of apoptotic bodies (P=0.013) and with the absence of necrosis (P=0.002). The
      presence of apoptotic bodies was correlated with re-distribution of PARP-1 from
      the nucleus to cytoplasm in BC cells (P=0.029). Additionally, a tendency was
      observed between necrosis and loss of nuclear PARP-1 expression (P=0.049). Our
      study suggests that PARP-1 may play a crucial role in induction and regulation of
      specific type of cellular death called parthanatos. 

PMID- 24441187
TI  - New insights into the in situ microscopic visualization and quantification of
      inorganic polyphosphate stores by 4',6-diamidino-2-phenylindole (DAPI)-staining.
AB  - Inorganic polyphosphate (PolyP) is a biological polymer that plays important
      roles in the cell physiology of both prokaryotic and eukaryotic organisms. Among
      the available methods for PolyP localization and quantification, a 4',6-diamidino
      2-phenylindole(DAPI)-based assay has been used for visualization of PolyP-rich
      organelles. Due to differences in DAPI permeability to different compartments
      and/or PolyP retention after fixation, a general protocol for DAPI-PolyP staining
      has not yet been established. Here, we tested different protocols for DAPI-PolyP
      detection in a range of samples with different levels of DAPI permeability,
      including subcellular fractions, free-living cells and cryosections of fixed
      tissues. Subcellular fractions of PolyP-rich organelles yielded DAPI-PolyP
      fluorescence, although those with a complex external layer usually required
      longer incubation times, previous aldehyde fixation and/or detergent
      permeabilization. DAPI-PolyP was also detected in cryosections of OCT-embedded
      tissues analyzed by multi-photon microscopy. In addition, a semi-quantitative
      fluorimetric analysis of DAPI-stained fractions showed PolyP mobilization in a
      similar fashion to what has been demonstrated with the use of enzyme-based
      quantitative protocols. Taken together, our results support the use of DAPI for
      both PolyP visualization and quantification, although specific steps are
      suggested as a general guideline for DAPI-PolyP staining in biological samples
      with different degrees of DAPI and PolyP permeability. 

PMID- 24441189
TI  - Knockdown of RAGE inhibits growth and invasion of gastric cancer cells.
AB  - The receptor for advanced glycation endproducts (RAGE) is an oncogenic trans
      membranous receptor, which is overexpressed in multiple human cancers. However,
      the role of RAGE in gastric cancer is still elusive. In this study, we
      investigated the expression and molecular mechanisms of RAGE in gastric cancer
      cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous
      tissues (ANCT) were collected, and the expression of RAGE was assessed using
      immunohistochemistry (IHC) in biopsy samples. Furthermore, RAGE signaling was
      blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv
      shRAGE) used to transfect into human gastric cancer SGC-7901 cells. The
      expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix
      metallopeptidase-2 (MMP-2) was detected by Real-time PCR and Western blot assays.
      Cell proliferative activities and invasive capability were respectively
      determined by MTT and Transwell assays. Cell apoptosis and cycle distribution
      were analyzed by flow cytometry. As a consequence, RAGE was found highly
      expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039), and
      correlated with lymph node metastases (P=0.026). Knockdown of RAGE reduced cell
      proliferation and invasion of gastric cancer with decreased expression of AKT,
      PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether,
      upregulation of RAGE expression is associated with lymph node metastases of
      gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of
      gastric cancer cells through AKT pathway, suggesting that RAGE may represent a
      potential therapeutic target for this aggressive malignancy. 

PMID- 24441190
TI  - Growth hormone plus resistance exercise attenuate structural changes in rat
      myotendinous junctions resulting from chronic unloading.
AB  - Myotendinous junctions (MTJs) are specialized sites on the muscle surface where
      forces generated by myofibrils are transmitted across the sarcolemma to the
      extracellular matrix. At the ultrastructural level, the interface between the
      sarcolemma and extracellular matrix is highly folded and interdigitated at these
      junctions. In this study, the effect of exercise and growth hormone (GH)
      treatments on the changes in MTJ structure that occur during muscle unloading,
      has been analyzed. Twenty hypophysectomized rats were assigned randomly to one of
      five groups: ambulatory control, hindlimb unloaded, hindlimb unloaded plus
      exercise (3 daily bouts of 10 climbs up a ladder with 50% body wt attached to the
      tail), hindlimb unloaded plus GH (2 daily injections of 1 mg/kg body wt, i.p.),
      and hindlimb unloaded plus exercise plus GH. MTJs of the plantaris muscle were
      analyzed by electron microscopy and the contact between muscle and tendon was
      evaluated using an IL/B ratio, where B is the base and IL is the interface length
      of MTJ's digit-like processes. After 10 days of unloading, the mean IL/B ratio
      was significantly lower in unloaded (3.92), unloaded plus exercise (4.18), and
      unloaded plus GH (5.25) groups than in the ambulatory control (6.39) group. On
      the opposite, the mean IL/B ratio in the group treated with both exercise and GH
      (7.3) was similar to control. These findings indicate that the interaction
      between exercise and GH treatments attenuates the changes in MTJ structure that
      result from chronic unloading and thus can be used as a countermeasure to these
      adaptations. 

PMID- 24441191
TI  - Endothelial barrier antigen-immunoreactivity is conversely associated with blood
      brain barrier dysfunction after embolic stroke in rats.
AB  - While the concept of the Neurovascular Unit (NVU) is increasingly recognized for
      exploring mechanisms of tissue damage in ischemic stroke, immunohistochemical
      analyses are of interest to specifically visualize constituents like the
      endothelium. Changes in immunoreactivity have also been discussed to reflect
      functional aspects, e.g., the integrity of the blood-brain barrier (BBB). This
      study aimed to characterize the endothelial barrier antigen (EBA) as addressed by
      the antibody SMI-71 in a rat model of embolic stroke, considering FITC-albumin as
      BBB leakage marker and serum levels of BBB-associated matrix metalloproteinases
      (MMPs) to explore its functional significance. Five and 25 h after ischemia
      onset, regions with decreased BBB integrity exhibited a reduction in number and
      area of EBA-immunopositive vessels, while the stained area per vessel was not
      affected. Surprisingly, EBA content of remaining vessels tended to be increased
      in areas of BBB dysfunction. Analyses addressing this interrelation resulted in a
      significant and inverse correlation between the vessels' EBA content and degree
      of BBB permeability. In conclusion, these data provide evidence for a functional
      relationship between EBA-immunoreactivity and BBB dysfunction in experimental
      ischemic stroke. Further studies are required to explore the underlying
      mechanisms of altered EBA-immunoreactivity, which might help to identify novel
      neuroprotective strategies. 

PMID- 24441192
TI  - An immunohistochemical study of matrix proteins in the craniofacial cartilage in
      midterm human fetuses.
AB  - Immunohistochemical localization of collagen types I, II, and X, aggrecan,
      versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein
      (MEPE) were performed for Meckel's cartilage, cranial base cartilage, and
      mandibular condylar cartilage in human midterm fetuses; staining patterns within
      the condylar cartilage were compared to those within other cartilaginous
      structures. Mandibular condylar cartilage contained aggrecan; it also had more
      type I collagen and a thicker hypertrophic cell layer than the other two types of
      cartilage; these three characteristics are similar to those of the secondary
      cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage
      matrix of all types of cartilage in the human fetuses and in Meckel's cartilage
      of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the
      hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in
      the primary spongiosa. These results indicated that MEPE is a component of
      cartilage matrix and may be involved in cartilage mineralization. DMP-1
      immunoreactivity first became evident in human bone lacunae walls and canaliculi;
      this pattern of expression was comparable to the pattern seen in rodents. In
      addition, chondroid bone was evident in the mandibular (glenoid) fossa of the
      temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1
      immunoreactivity; these findings indicated that chondroid bone in this region has
      phenotypic expression indicative of both hypertrophic chondrocytes and
      osteocytes. 

PMID- 24441193
TI  - Localization of alphanubeta6 integrin-TGF-beta1/Smad3, mTOR and PPARgamma in
      experimental colorectal fibrosis.
AB  - A simultaneous action of several pro-fibrotic mediators appears relevant in the
      development of fibrosis. There are evidences that transforming growth factor-beta
      (TGF-beta)/Smad3 pathway forms with alphavbeta6 integrin, mammalian target of
      Rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma (PPARgamma)
      a complex signalling network with extensive crosstalk and strong effects on
      fibrosis development. The present study evaluated the expression of TGFbeta,
      Smad3, alphavbeta6 integrin, mTOR and PPARgamma in 2,4,6-trinitrobenzenesulphonic
      acid (TNBS)-induced colorectal fibrosis in Smad3 wild-type (WT) and null mice.
      Smad3 WT mice treated with TNBS developed a marked colorectal fibrosis and showed
      a concomitant up-regulation of TGFbeta, Smad3, alphavbeta6 and mTOR and a
      reduction of PPARgamma expression. On the other hand, Smad3 Null mice similarly
      treated with TNBS did not develop fibrosis and showed a very low or even absent
      expression of TGFbeta, Smad3, alphavbeta6 and mTOR and a marked over-expression
      of PPARgamma. At the same time the expression of alpha-smooth muscle actin (a
      marker of activated myofibroblasts), collagen I-III and connective tissue growth
      factor (a downstream effector of TGFbeta/Smad3-induced extracellular matrix
      proteins) were up-regulated in Smad3 WT mice treated with TNBS compared to Null
      TNBS-treated mice. These preliminary results suggest a possible interaction
      between these pro-fibrotic molecules in the development of intestinal fibrosis.

PMID- 24441197
TI  - HCN channels: new roles in sinoatrial node function.
AB  - Hyperpolarization-activated cyclic nucleotide gated (HCN) channels pass a
      cationic current (Ih/If) that crucially contributes to the slow diastolic
      depolarization (SDD) of sinoatrial pacemaker cells and, hence, is a key
      determinant of cardiac automaticity and the generation of the heart beat. There
      is growing evidence, that HCN channel functions in the sinoatrial node (SAN) are
      not restricted to impulse formation but are also required for impulse
      propagation. In addition, HCN channels are involved in coordination and
      maintenance of sinoatrial network activity and, hence, are crucial for
      stabilizing cardiac rhythmicity. In the present review we will outline these new
      concepts. 

PMID- 24441194
TI  - Histochemistry as an irreplaceable approach for investigating functional cytology
      and histology.
AB  - In agreement with the evolution of histochemistry over the last fifty years and
      thanks to the impressive advancements in microscopy sciences, the application of
      cytochemical techniques to light and electron microscopy is more and more
      addressed to elucidate the functional characteristics of cells and tissue under
      different physiological, pathological or experimental conditions. Simultaneously,
      the mere description of composition and morphological features has become
      increasingly sporadic in the histochemical literature. Since basic research on
      cell functional organization is essential for understanding the mechanisms
      responsible for major biological processes such as differentiation or growth
      control in normal and tumor tissues, histochemical Journals will continue to play
      a pivotal role in the field of cell and tissue biology in all its structural and
      functional aspects. 

PMID- 24441199
TI  - From the editor.

PMID- 24441198
TI  - DNA methylome profiling identifies novel methylated genes in African American
      patients with colorectal neoplasia.
AB  - The identification of genes that are differentially methylated in colorectal
      cancer (CRC) has potential value for both diagnostic and therapeutic
      interventions specifically in high-risk populations such as African Americans
      (AAs). However, DNA methylation patterns in CRC, especially in AAs, have not been
      systematically explored and remain poorly understood. Here, we performed DNA
      methylome profiling to identify the methylation status of CpG islands within
      candidate genes involved in critical pathways important in the initiation and
      development of CRC. We used reduced representation bisulfite sequencing (RRBS) in
      colorectal cancer and adenoma tissues that were compared with DNA methylome from
      a healthy AA subject's colon tissue and peripheral blood DNA. The identified
      methylation markers were validated in fresh frozen CRC tissues and corresponding
      normal tissues from AA patients diagnosed with CRC at Howard University Hospital.
      We identified and validated the methylation status of 355 CpG sites located
      within 16 gene promoter regions associated with CpG islands. Fifty CpG sites
      located within CpG islands-in genes ATXN7L1 (2), BMP3 (7), EID3 (15), GAS7 (1),
      GPR75 (24), and TNFAIP2 (1)-were significantly hypermethylated in tumor vs.
      normal tissues (P<0.05). The methylation status of BMP3, EID3, GAS7, and GPR75
      was confirmed in an independent, validation cohort. Ingenuity pathway analysis
      mapped three of these markers (GAS7, BMP3 and GPR) in the insulin and TGF-beta1
      network-the two key pathways in CRC. In addition to hypermethylated genes, our
      analysis also revealed that LINE-1 repeat elements were progressively
      hypomethylated in the normal-adenoma-cancer sequence. We conclude that DNA
      methylome profiling based on RRBS is an effective method for screening aberrantly
      methylated genes in CRC. While previous studies focused on the limited
      identification of hypermethylated genes, ours is the first study to
      systematically and comprehensively identify novel hypermethylated genes, as well
      as hypomethylated LINE-1 sequences, which may serve as potential biomarkers for
      CRC in African Americans. Our discovered biomarkers were intimately linked to the
      insulin/TGF-B1 pathway, further strengthening the association of diabetic
      disorders with colon oncogenic transformation. 

PMID- 24441200
TI  - Unemployed long-term sicklisted people in rural Jamtland compared with
      circumstances in the city of Stockholm, Sweden.
AB  - OBJECTIVES: The dual aims of this study were to investigate the unemployed
      sicklisted in an area of rural northern Sweden and to compare the results with
      results obtained earlier from the city of Stockholm. STUDY DESIGN: Data were
      obtained mainly from the social insurance office registers. The study covers 795
      cases. RESULTS: The results show the unexpected finding that the proportion of
      unemployed among sicklisted people was lower in the northern rural area (15%)
      than in Stockholm (20%). Mental diagnoses were, as in Stockholm, more common
      among the unemployed, especially among the men. In Jamtland it is more common for
      the employed to leave the social insurance system after sick leave than is the
      case for the unemployed. The latter, instead, tend to start a new period of sick
      leave or a period on rehabilitation allowance. In Stockholm it was more common
      that the unemployed compared with the employed replaced a sick period with a
      temporary disability pension. CONCLUSIONS: The study indicates that the
      unemployed sicklisted people are a group with special needs concerning
      rehabilitation. This poses a special challenge to the rehabilitation counsellors
      working with the unemployed.

PMID- 24441201
TI  - Analysis of approaches to detection of sincerity of effort through grip strength
      measurement.
AB  - Due to a variety of psychological and/or economic reasons, the validity of grip
      strength measurement to assess physical characteristics, progress in
      rehabilitation and degree of disability is sometimes compromised by a subject's
      deliberate submaximal performance. This paper analyzes the reliability and
      validity of various approaches used to detect sincerity of effort through grip
      strength measurement. Studies basing methodologies on the bell-shaped curve
      theory, cortical control theory, analysis of force relationships, use of
      coefficient of variation, and EMG techniques are examined. Strengths and
      limitations to each approach are discussed. Implications for future research are
      stated. 

PMID- 24441202
TI  - Documenting the need for transition services at an earlier age.
AB  - Though the reconciliation between the US Senate and House of Representatives on
      reauthorization of the Individuals with Disabilities Education Act Amendments
      (IDEA) was not successful in 1996, one area of agreement was the lowering of the
      age to begin transition services planning to 14. The current study provides
      documentation in support of this policy change. The enrollment records over a 5
      year period of more than 7000 students were examined in Delaware public schools
      for the Class of 1995 to determine whether the exiting rates were different for
      students with and without a disability. Results indicate that students with a
      disability exited school at a significantly greater rate in grade 9 than their
      regular education peers; exited at almost double the rate in grade 10; and
      continued to exit at an alarming rate even in grade 12. Thus the need to begin
      effective transition services planning at age 14 or earlier is supported by this
      study of longitudinal data. 

PMID- 24441203
TI  - Maintaining work capacity in the aged worker via progressive resistance training:
      the implications for occupational therapy practitioners.
AB  - Society has an interest in maintaining the work capacity of its aging workers.
      Fewer and fewer younger workers are entering the workforce to replace older
      citizens no longer able to perform the worker role. There is a demonstrated
      relationship between increased strength and work capacity, yet the occupational
      therapy literature emphasizes generalized exercise programming. This type of
      programming is ineffective at building strength in the elderly worker. High
      intensity progressive resistance exercise (PRE) can increase strength in the very
      old worker, yet therapists are hesitant to employ PRE, perhaps due to a potential
      bias against the use of high intensity PRE with this cohort. Use of PRE may
      present some difficulties in the clinical situation where continual supervision
      and resistance training equipment is not available. The adaptive use of
      functional activities as a resistance training strategy to build strength may be
      able to overcome the difficulties attendant with the use of PRE while preserving
      its benefits. Several other implications for occupational therapy practitioners
      are discussed. 

PMID- 24441204
TI  - OSHAs proposed ergonomic standards: impacts and outcomes.
AB  - OSHAs role in ergonomics is reviewed and recommendations for control of work
      related musculoskeletal disorders are summarized. The potential impact of these
      proposed regulations is discussed. A case review of a food manufacturing plant
      implementing portions of these ergonomics guidelines is presented and preliminary
      outcomes are highlighted. 

PMID- 24441205
TI  - Cognitive-behavioral therapy: a psychoeducational treatment approach for the
      American worker with rheumatoid arthritis.
AB  - Rheumatoid arthritis is a systemic autoimmune disorder affecting nearly 2.1
      million Americans. This condition often leads to chronic pain, inflammation,
      joint destruction, feelings of helplessness, maladaptive coping, depression and
      activity limitations. For those individuals with rheumatoid arthritis and chronic
      arthritic pain, the role of the worker has become difficult to maintain. Research
      suggests that cognitive-behavioral intervention reduces chronic arthritic pain,
      decreases disease activity and improves coping skills in individuals with
      rheumatoid arthritis. To be effective, cognitive-behavioral techniques must be
      practiced on a regular basis. The literature suggests that the American worker
      with rheumatoid arthritis would greatly benefit from work-site wellness programs
      that provide cognitive-behavioral intervention as a 'reasonable accommodation'.
      Occupational therapy practitioners can help to advance the positive effects of
      this psychoeducational intervention by providing 'booster treatments' to clients
      after formal treatment sessions have ceased. 

PMID- 24441206
TI  - Back school or pamphlet education: which is best for industry?
AB  - The use of education in the clinical setting to help chronic sufferers cope with
      their back pain is not a new concept. Back schools and work hardening programs
      have been running for many years, but education about back pain at the primary
      care level, in industry specifically, has been slower in developing. Studies that
      have used back schools in industry have had some success but not as much as might
      be hoped, often not being very cost-efficient nor producing lasting changes in
      health behaviours. However, the use of educational pamphlets in the primary care
      setting have shown success in changing individuals knowledge about back pain and
      altering number of visits to a physician. Furthermore, when a pamphlet, designed
      on the basis of current knowledge about the management of non-specific low back
      pain, was distributed in a manufacturing industry, there were changes in beliefs
      about back pain which mirrored substantial change in absence behaviour. In
      conclusion, education through the medium of a pamphlet seems able to change
      knowledge and behaviours related to back pain and, with sufficiently large
      reductions in absence from the workplace it would appear to be a cost-efficient
      method. Further studies are required to confirm the validity and cost-efficiency
      of pamphlet education for back pain in the manufacturing industry, but also to
      determine pamphlet utility in other work environments and for other health
      problems. 

PMID- 24441207
TI  - The working alliance: an interdisciplinary case management strategy for health
      professionals.
AB  - This article describes strategies for building working alliances among
      stakeholders in the rehabilitation process. Beginning with the intake interview
      and progressing through clarifying expectations, establishing bonds, setting
      goals, formulating tasks and resolving conflicts, the working alliance provides a
      model for meeting a wide range of client needs in a comprehensive, cost-effective
      manner. 

PMID- 24441208
TI  - Burden of proof in detection of submaximal effort.
AB  - The recent increase in workers' compensation litigation and the escalating costs
      of healthcare have created a need for accurate identification of individuals who
      put forth submaximal effort during functional capacity testing. This paper
      reviews methods healthcare professionals can use to prove submaximal efforts and
      specifically addresses the importance of test reliability, subjective and
      objective measures of submaximal effort (including the DASH questionnaire, 5-rung
      and rapid exchange grip strength measures, forced-choice testing and the MMPI),
      techniques used to elicit maximal effort and test accuracy and patient
      motivations and examiner biases. Use of these methods will contribute to the
      establishment of a functionally sound healthcare system. 

PMID- 24441209
TI  - Hand injury and electrical tools.
AB  - This case study looks at an electrician who sustained two hand injuries due to
      tool use. The first injury was a ganglionic cyst in the right palm and the second
      was a cyst in the right thumb. Recommendations from The Job Accommodation Network
      (JAN) and his company's insurance company are included. 

PMID- 24441210
TI  - Functional capacity evaluation as a facilitator of social security disability
      program reform.

PMID- 24441211
TI  - Malaria.
AB  - Malaria remains a significant health threat to the world's population. Increases
      in international travel and migration; climatic changes; resistance to
      insecticides and antimalarial drugs all contribute to the enduring nature of the
      disease. Poverty is a key factor in determining who will succumb. 

PMID- 24441213
TI  - A test of the metabolic cost of cushioning hypothesis during unshod and shod
      running.
AB  - PURPOSE: This study aimed to investigate the effects of surface and shoe
      cushioning on the metabolic cost of running. In running, the leg muscles generate
      force to cushion the impact with the ground. External cushioning (surfaces or
      shoes) may reduce the muscular effort needed for cushioning and thus reduce
      metabolic cost. Our primary hypothesis was that the metabolic cost of unshod
      running would decrease with a more cushioned running surface. We also
      hypothesized that because of the counteracting effects of shoe cushioning and
      mass, unshod running on a hard surface would have approximately the same
      metabolic cost as running in lightweight, cushioned shoes. METHODS: To test these
      hypotheses, we attached 10- and 20-mm-thick slats of the same foam cushioning
      used in running shoe midsoles to the belt of a treadmill that had a rigid deck.
      Twelve subjects who preferred a midfoot strike pattern and had substantial
      barefoot/minimalist running experience ran without shoes on the normal treadmill
      belt and on each thickness of foam. They also ran with lightweight, cushioned
      shoes on the normal belt. We collected VO2 and VCO2 to calculate the metabolic
      power demand and used a repeated-measures ANOVA to compare between conditions.
      RESULTS: Compared to running unshod on the normal belt, running unshod on the 10
      mm-thick foam required 1.63% +/- 0.67% (mean +/- SD) less metabolic power (P =
      0.034) but running on the 20-mm-thick foam had no significant metabolic effect.
      Running with and without shoes on the normal belt had similar metabolic power
      demands, likely because the beneficial energetic effects of cushioning
      counterbalanced the detrimental effects of shoe mass. CONCLUSIONS: On average,
      surface and shoe cushioning reduce the metabolic power required for submaximal
      running.

PMID- 24441214
TI  - Mechanical and muscular coordination patterns during a high-level fencing
      assault.
AB  - PURPOSE: This study aimed to investigate the coordination of lower limb muscles
      during a specific fencing gesture in relation to its mechanical effectiveness.
      METHODS: Maximal isokinetic concentric and isometric plantarflexor, dorsiflexor,
      knee and hip extensor and flexor torques of 10 female elite saber fencers were
      assessed and compared between both legs. Sabers completed three trials of a
      specific fencing gesture (i.e., marche-fente) on a 6.60-m-long force platform
      system. Surface EMG activities of 15 lower limb muscles were recorded in time
      with ground reaction forces and separated into four distinct assault phases. EMG
      signals were normalized to the muscle activity assessed during maximal isometric
      contraction. Mechanical and EMG data were compared between both legs over the
      entire assault and in each phase (ANOVA). Potential correlations between muscle
      strength and average EMG activities were tested (Bravais-Pearson coefficient).
      RESULTS: EMG activity patterns showed that rear hip and knee extensor and
      plantarflexor muscles were mainly activated during propulsive (concentric)
      phases, while front hip and knee extensor muscles were strongly solicited during
      the final braking (eccentric) phase to decelerate the body mass. Although fencers
      presented greater maximal hip (+10%) and knee (+26%) extensor strength in the
      front than in the rear leg (P < 0.05), rear hip and knee extensor strength was
      significantly correlated to the maximal anteroposterior velocity (r = 0.60-0.81).
      Moreover, muscle activity of the rear extensors was related to average velocity
      during the second propulsive phase (phase 3). CONCLUSIONS: This study gathers the
      first evidence of a crucial role of the rear extensor muscles in fencing speed
      performance. Such findings suggest interesting perspectives in the definition of
      specific training or rehabilitation programs for elite fencers.

PMID- 24441215
TI  - Integrated resistance and aerobic exercise protects fitness during bed rest.
AB  - INTRODUCTION: The current exercise countermeasures have not fully protected
      astronauts' preflight aerobic and muscular fitness levels during International
      Space Station (ISS) missions, prompting a need to optimize the exercise
      prescription to improve or maintain astronauts' ability to perform critical tasks
      and eventually extend the duration of missions. PURPOSE: To test the hypothesis
      that an integrated resistance and aerobic exercise prescription performed with
      exercise equipment similar to that on the ISS can be tolerated and maintain
      cardiovascular and muscular fitness during 14 d of exposure to a model of
      microgravity. METHODS: Subjects (n = 9) participated in 14-21 d of pre-bed rest
      training and familiarization, 14 d of bed rest + iRAT exercise, and 7 d of
      ambulatory recovery. Peak aerobic capacity (VO2peak), ventilatory threshold (VT),
      and isokinetic and leg press tests were performed before and after bed rest to
      evaluate cardiovascular and muscle functions. Muscle cross-sectional area (CSA)
      was determined before, during, and after bed rest using magnetic resonance
      imaging (MRI). RESULTS: Improvements from before to after bed rest were observed
      in VO2peak (2.8 +/- 0.2 to 3.2 +/- 0.2 L.min(-1)), VT (1.9 +/- 0.2 to 2.1 +/- 0.2
      L.min(-1)), leg muscle power (1582 +/- 317 to 1740 +/- 359 W), and muscle CSA of
      the grouped vastus lateralis, vastus intermedius, and vastus medialis muscles
      (67.5 +/- 8.4 to 68.9 +/- 8.3 cm). Muscle strength and total CSA of the upper and
      lower legs were not different from before to after bed rest. CONCLUSIONS: This is
      the first report of exercise being completely effective for the prevention of
      cardiovascular and skeletal muscle deconditioning during strict bed rest using
      exercise equipment similar to that on the ISS. This was accomplished with high
      subject compliance.

PMID- 24441216
TI  - Psychophysiological effects of synchronous versus asynchronous music during
      cycling.
AB  - PURPOSE: Synchronizing movement to a musical beat may reduce the metabolic cost
      of exercise, but findings to date have been equivocal. Our aim was to examine the
      degree to which the synchronous application of music moderates the metabolic
      demands of a cycle ergometer task. METHODS: Twenty-three recreationally active
      men made two laboratory visits. During the first visit, participants completed a
      maximal incremental ramp test on a cycle ergometer. At the second visit, they
      completed four randomized 6-min cycling bouts at 90% of ventilatory threshold
      (control, metronome, synchronous music, and asynchronous music). Main outcome
      variables were oxygen uptake, HR, ratings of dyspnea and limb discomfort,
      affective valence, and arousal. RESULTS: No significant differences were evident
      for oxygen uptake. HR was lower under the metronome condition (122 +/- 15 bpm)
      compared to asynchronous music (124 +/- 17 bpm) and control (125 +/- 16 bpm).
      Limb discomfort was lower while listening to the metronome (2.5 +/- 1.2) and
      synchronous music (2.3 +/- 1.1) compared to control (3.0 +/- 1.5). Both music
      conditions, synchronous (1.9 +/- 1.2) and asynchronous (2.1 +/- 1.3), elicited
      more positive affective valence compared to metronome (1.2 +/- 1.4) and control
      (1.2 +/- 1.2), while arousal was higher with synchronous music (3.4 +/- 0.9)
      compared to metronome (2.8 +/- 1.0) and control (2.8 +/- 0.9). CONCLUSIONS:
      Synchronizing movement to a rhythmic stimulus does not reduce metabolic cost but
      may lower limb discomfort. Moreover, synchronous music has a stronger effect on
      limb discomfort and arousal when compared to asynchronous music.

PMID- 24441217
TI  - Stereochemical and conformational study on fenoterol by ECD spectroscopy and TD
      DFT calculations.
AB  - Fenoterol and its derivatives are selective beta2-adrenergic receptor (beta2-AR)
      agonists whose stereoselective biological activities have been extensively
      investigated in the past decade; a complete stereochemical characterization of
      fenoterol derivatives is therefore crucial for a better understanding of the
      effects of stereochemistry on beta2-AR binding. In the present project, the
      relationship between chiroptical properties and absolute stereochemistry of the
      stereoisomers of fenoterol (1) was investigated by experimental ECD spectroscopy
      and time-dependent density functional theory (TD-DFT). DFT geometry optimizations
      were carried out at the RI-B97D/TZVP/IEFPCM(MeOH) level and subsequent TD-DFT
      calculations were performed using the PBE0 hybrid functional. Despite the large
      pool of equilibrium conformers found for the investigated compounds and the known
      limitations of the level of theory employed, the computational protocol was able
      to reproduce the experimental ECD spectra of the stereoisomers of 1. The main
      contribution to the overall chiroptical properties was found to arise from the
      absolute configuration of the chiral center in alpha-position to the resorcinol
      moiety. Based on this evidence, a thorough conformational analysis was performed
      on the optimized DFT conformers, which revealed the occurrence of a different
      equilibrium between conformational patterns for the diastereomers of fenoterol:
      the (R,R')/(S,S') enantiomeric pair showed a higher population of folded
      conformations than the (R,S')/(S,R') pair. 

PMID- 24441218
TI  - From editor's desk.

PMID- 24441219
TI  - Increased accumulation of dendritic cells in celiac disease associates with
      increased expression of autophagy protein LC3.
AB  - BACKGROUND: Celiac disease (CD) an immune-mediated disorder associates with
      accumulation of dendritic cell (DC) in duodenal mucosa. Autophagy has recently
      been implicated in autoantigen formation. However, its role in CD is still
      unknown. AIM: To examine role of autophagic protein LC3 expressed by activated DC
      in CD. MATERIALS AND METHODS: Thirty CD patients were analyzed at initial
      presentation and after 6 months of gluten-free diet (GFD). Duodenal biopsies were
      studied for histological changes and CD11c, CD86, and MAP1LC3A expressions by
      double immunohistochemistry (IHC). Masson's trichrome (MT) staining was used to
      assess basement membrane (BM) thickness and Oil Red O (ORO) staining for mucosal
      lipid deposit. Polymerase chain reaction (PCR) was performed for HLA-DQ system.
      Statistical analysis was done using paired and unpaired t test, chi-square test,
      Fisher's exact test, and McNemar-Bowker test. A P-value <0.05 was considered
      statistically significant. RESULTS: HLA-DQ2 and HLA-DQ8 alleles were present in
      all studied patients. Increased BM thickness was observed in 63% and 73% had ORO
      positive lipid in surface lining epithelium. Pre-treatment biopsies showed
      increased DCs expressing LC3, which were significantly less in follow-up
      biopsies. The follow-up biopsies had shown significant reduction in BM thickness
      and ORO. CONCLUSION: Histological improvement in duodenal biopsies was associated
      with reduction in activated DCs expressing autophagic protein, which probably
      play important role in pathogenesis of an autoimmune disorder like CD.

PMID- 24441220
TI  - Vascular endothelial growth factor expression and angiogenesis in various grades
      and subtypes of meningioma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) expression has been
      extensively studied in astrocytoma, whereas relatively less literature exists on
      VEGF expression in meningioma. MATERIALS AND METHODS: Patients operated for
      meningioma from 2006 to 2011 (n = 46) were included. Tumor was subtyped and
      graded as per WHO grading. Immunohistochemistry was performed for MIB labeling
      index, VEGF, and CD 34 staining. The patterns of VEGF expression in various
      histological subtypes and grades and its correlation with microvascular density
      were analyzed. RESULTS: This series consisted of 40 Grade I meningioma, 4 Grade
      II tumors, and 2 Grade III tumors. While 14 (30.4%) tumors showed no staining
      with VEGF antibody, 32 (69.6%) were positive for VEGF. Sixty five percent of
      Grade I tumors showed VEGF positivity, while 100% of Grade II and Grade III
      tumors were VEGF positive (P = 0.157). The mean microvascular density in VEGF
      negative tumors was 9.00, while that of VEGF-positive tumors was 17.81(P =
      0.013). There was a gradual increase in microvascular density from tumors which
      are negative for VEGF to tumors which expressed moderate to strong VEGF, the
      difference being statistically significant (P = 0.009). CONCLUSIONS: VEGF
      expression correlated with the microvascular density in meningioma irrespective
      of tumor grade, with a gradual increase in microvascular density in relation to
      the VEGF score.

PMID- 24441222
TI  - Association of Epstein Barr virus deoxyribonucleic acid with lung carcinoma.
AB  - CONTEXT: Lung cancer is the leading cause of cancer death worldwide. In addition
      to smoking, a variety of other contributing factors, including viral infection,
      have been suggested in tumorigenesis. Epstein Barr virus (EBV), which is linked
      to various malignancies, seems to be a good candidate. AIMS: The aim of this
      study was to investigate the association of EBV with lung carcinomas. SETTINGS
      AND DESIGN: A total number of 90 formalin fixed paraffin embedded lung tissue
      samples including 48 cases of lung cancers (18 squamous cell carcinomas [SCCs],
      18 adenocarcinomas and 12 small cell carcinomas) and 42 non-tumoral samples
      (control group), were retrieved from the pathology archive. MATERIALS AND
      METHODS: Following deoxyribonucleic acid extraction, polymerase chain reaction
      (PCR) was performed using an EBV-Eph PCR kit. The positive cases were studied
      immunohistochemically for the expression of EBV-late membrane protein-1 (EBV-LMP
      1) in tumoral tissues. STATISTICAL ANALYSIS USED: The t-test and Fisher exact
      test were used and P < 0.05 was considered statistically significant. RESULTS:
      Five of our cases, including four SCCs and one adenocarcinoma and two control
      samples showed a positive reaction in PCR. All positive tumoral cases showed
      diffuse staining with LMP-1 in immunohistochemistry. CONCLUSIONS: We found a
      significant difference in the presence of the EBV genome in cases of lung SCC
      compared to other lung lesions (P = 0.02). According to our data, EBV is not at
      major play in the non-lymphoepithelioma-like cancers of the lung in general, but
      may have a role in the tumorigenesis of some lung SCCs.

PMID- 24441221
TI  - Perforating disorders of the skin.
AB  - BACKGROUND: Perforating disorders of the skin, is an often overlooked entity
      characterized by transepidermal elimination of material from the upper dermis and
      are classified histopathologically according to the type of epidermal disruption
      and the nature of the eliminated material. They include Kyrle's disease,
      perforating folliculitis, reactive perforating collagenosis, and elastosis
      perforans serpiginosa. AIM: The aim of this study was to delineate the clinical
      and histopathological features of perforating disorders of the skin. MATERIALS
      AND METHODS: In our study, we reviewed last 2 years skin biopsies received by us.
      Hematoxylin and eosin sections were re-examined and histochemical stainings
      (elastic van Gieson and Masson trichrome stains) were also used for
      histopathological evaluation. RESULTS: We reviewed five cases of perforating
      disorders of skin which included two cases of Kyrle's disease, two cases of
      reactive perforating collagenosis and a single case of perforating folliculitis.
      Two patients had family history of perforating dermatosis in their siblings and
      three had associated systemic disease. CONCLUSION: Perforating disorders of the
      skin should be considered when ulcer with keratotic plugs is found.

PMID- 24441223
TI  - Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors
      (OMMMT) from a tertiary cancer institute: A series of 27 cases.
AB  - AIMS AND OBJECTIVES: To study the clinico-pathological characteristics of primary
      ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors
      associated with treatment outcome and survival. MATERIALS AND METHODS: The
      pathology database was searched for primary ovarian carcinosarcoma diagnosed
      and/or managed at our institute from period of January 2004 to July 2010. The
      histological sections were reviewed, with emphasis on type and grade of
      epithelial and sarcomatous components. The medical records were retrospectively
      analyzed for clinical details and follow up. RESULTS: A total of 27 cases of
      primary ovarian carcinosarcoma were identified. The median age at diagnosis was
      51 years. Fourteen patients had advanced stage (stage III and IV) at
      presentation. Cytoreductive surgery was done in 18 cases, and 7 had received
      upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50%
      epithelial component) and 11 had sarcoma predominance. The most frequent
      epithelial component was endometroid type, and most common sarcoma component was
      rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen
      prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas.
      Eighteen cases had follow up with a median of 15 months (4-40 months). The
      recurrence-free survival in advanced stage and sarcoma predominant was 10.5
      months in comparison to 13 months in early stage and epithelial predominant
      OMMMT. CONCLUSION: Primary ovarian carcinosarcoma is a rare biphasic malignancy
      with variable proportions of epithelial and spindle elements. Presence of hyaline
      droplets within spindle sarcoma in a biopsy from ovarian mass should alert the
      pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and
      sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.

PMID- 24441224
TI  - Is necropsy obsolete - an audit of the clinical autopsy over six decades: a study
      from Indian sub continent.
AB  - INTRODUCTION: Several studies have documented a decrease in the autopsy rate.
      This study was taken up to analyse the cause of mortality, the discrepancies
      between the ante mortem and post mortem diagnosis and the discrepancies between
      diagnoses according to the type of the disease over a period of six decades.
      MATERIALS AND METHODS: Autopsy reports and medical records were retrospectively
      analyzed over a 63 year period from 1947 to 2010. RESULTS: In our study, there
      was a steady increase in the percentage of neoplastic cases from 1947 to 1994
      after which there has been a significant drop. The cases dying due to infection
      has also shown a steady decline over the years until 1994. After 1994, there has
      been a significant increase in the deaths until 2010 (p < 0.05). Death due to
      cardiac causes has shown an increase until 1962 which has been followed by a
      steady decline. There has been a sudden rise in the number of cases dying due to
      renal causes between 1994 and 2000 (p < 0.05). There has been a statistically
      significant decrease in the discrepancies between the ante mortem and the post
      mortem diagnosis over the years. DISCUSSION: This study shows that therapeutic
      and preventive measures correctly instituted have significantly reduce the
      mortality, particularly with reference to cardiac and infectious causes. The
      discrepancy between antemortem and post-mortem diagnosis in 2010 is still very
      high at 9.30 percent. The autopsy will continue to remain relevant especially in
      elucidating the molecular cause of disease.

PMID- 24441225
TI  - Red cell alloimmunization and infectious marker status (human immunodeficiency
      virus, hepatitis B virus and hepatitis C virus) in multiply transfused
      thalassemia patients of North India.
AB  - BACKGROUND: Patients with thalassemia major are largely transfusion dependent and
      are thus exposed to a variety of risks such as transmission of infectious
      diseases, iron overload and alloimmunization. This study was performed to
      determine the prevalence of human immune deficiency virus (HIV), hepatitis B
      virus (HBV), hepatitis C virus (HCV) and red cell antibodies among multiple
      transfused thalassemic patients in and around the national capital region.
      MATERIALS AND METHODS: The Department of Transfusion Medicine, Indraprastha
      Apollo Hospitals, conducted this study in collaboration with the National
      Thalassemia Welfare Society over a period of 1 year starting February2011. Blood
      samples from the patients were tested for blood group, red cell alloantibody/ies,
      anti-HIV, anti-HCV and hepatitis B surface antigen (HBsAg) by ELISA and for the
      respective viral ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) by nucleic
      acid testing (NAT). RESULTS: A total of 462 thalassemics which consists of 290
      males and 172 females were tested. The overall alloimmunization rate was 4.1% and
      anti-Kell was the most common antibody identified. Thirteen cases (2.8%) were
      positive for HBsAg by ELISA, 107 (23.1%) were reactive for anti HCV and 11
      (2.38%) for anti HIV antibodies. Further screening and discriminatory assays by
      NAT confirmed the presence of HBV DNA in 11 cases, HIV RNA in 7 cases and HCV RNA
      in 48 cases. CONCLUSION: In spite of advances in Immunohematology and infectious
      marker testing in recent years, the rates of alloimmunization and infectious
      marker positivity remains high among multiply transfused patients like
      thalassemics. Provision of safe and adequate blood supply to these patients is a
      key to improving their quality-of-life and longevity.

PMID- 24441226
TI  - Hepatitis C virus genotypes: a plausible association with viral loads.
AB  - BACKGROUND AND AIM: The basic aim of this study was to find out the association
      of genotypes with host age, gender and viral load. MATERIAL AND METHODS: The
      present study was conducted at Social Security Hospital, Pakistan. This study
      included 320 patients with chronic hepatitis C virus (HCV) infection who were
      referred to the hospital between November 2011 and July 2012. HCV viral detection
      and genotyping was performed and the association was seen between genotypes and
      host age, gender and viral load. RESULTS: The analysis revealed the presence of
      genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b +
      3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV
      ribonucleic acid (RNA) positive patients. The genotype 3a was observed in 124
      (82.12%) patients, 3b was found in 21 (13.91%), 1a was seen in 2 (1.32%), 1b in 1
      (0.66%), mixed infection with 1b + 3a in 1 (0.66%), 1b + 3b in 1 (0.66%) and 3a +
      3b was also found in 1 (0.66%) patient. Viral load quantification was carried out
      in all 151 HCV RNA positive patients and was compared between the various
      genotypes. The mean viral load in patients infected with genotype 1a was 2.75 *
      10 6 , 1b 3.9 * 10 6 , 3a 2.65 * 10 6 , 3b 2.51 * 10 6 , 1b + 3a 3.4 * 106, 1b +
      3b 2.7 * 106 and 3a + 3b 3.5 * 10 6 . An association between different types of
      genotypes and viral load was observed. CONCLUSION: Further studies should be
      carried out to determine the association of viral load with different genotypes
      so that sufficient data is available and can be used to determine the type and
      duration of therapy needed and predict disease outcome.

PMID- 24441227
TI  - Bacterial profile and patterns of antimicrobial drug resistance in intra
      abdominal infections: current experience in a teaching hospital.
AB  - CONTEXT: Bacterial isolates from intra-abdominal infections, in particular,
      peritonitis and their unpredictable antimicrobial resistance patterns, continue
      to be a matter of concern not only globally but regionally too. AIM: An attempt
      in the present study was made to study the patterns of drug resistance in
      bacterial isolates, especially gram negative bacilli in intra-abdominal
      infections (IAI) in our hospital. MATERIALS AND METHODS: From 100 cases of
      peritonitis, identification of isolates was done as per recommended methods.
      Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) testing
      were performed following the CLSI guidelines. RESULTS: A total of 133 clinical
      isolates were obtained, of which 108 were aerobes and 22 anaerobes. Fungal
      isolates were recovered in only three cases. Escherichia coli (47/108) emerged as
      the most predominant pathogen followed by Klebsiella spp. (27/108), while
      Bacteroides fragilis emerged as the predominant anaerobe (12/22). Among
      coliforms, 61.7% E. coli and 74.1% Klebsiella spp. were ESBL positive. A high
      level of resistance was observed for beta lactams, ciprofloxacin, amikacin, and
      ertapenem. Ertapenem resistance (30-41%) seen in coliforms, appears as an
      important issue. Imipenem, tigecycline, and colistin were the most consistently
      active agents tested against ESBL producers. CONCLUSION: Drug resistance
      continues to be a major concern in isolates from intra-abdominal infections.
      Treatment with appropriate antibiotics preceded by antimicrobial resistance
      testing aided by early diagnosis, adequate surgical management, and knowledge of
      antibiotic - resistant organisms appears effective in reducing morbidity and
      mortality in IAI cases.

PMID- 24441228
TI  - Conventional renal cell carcinoma with renal capsular leiomyoma: a diagnostic
      dilemma.
AB  - Primary renal leiomyomas are very rare benign tumors of the kidney, arising from
      smooth muscle cells of the renal capsule, pelvis or blood vessels. Simultaneous
      occurrence of a leiomyoma with conventional renal cell carcinoma (RCC) in the
      same kidney is an extremely rare incidence. Herein we describe a case, which to
      the best of our knowledge is the second reported case in the English literature.
      This 70-year-old female presented in surgical out-patient department with the
      complaints of hematuria and abdominal pain. Subsequently, on computed tomography
      a multifocal mass was noted in the right kidney, measuring 4.5 cm Chi 3 cm Chi 2
      cm and 1 cm Chi 0.5 cm Chi 0.5 cm respectively. A radical nephrectomy was
      performed with the clinical diagnosis of a multifocal RCC. Histopathological
      examination revealed a conventional RCC in the larger nodule, whereas the smaller
      nodule showed a sub capsular leiomyoma, which was immune-positive for smooth
      muscle actin and HMB45. In the index case, radiology could not differentiate
      between the RCC and leiomyoma. Apart from being a radiological diagnostic
      dilemma, rare HMB45 immunostain positivity in capsular leiomyoma may create
      diagnostic dilemma for histopathologists too. Sole HMB45 positivity should not
      distract one to diagnose this lesion as an angiomyolipoma, unless the other
      components are seen. 

PMID- 24441229
TI  - Dumb-bell shaped poorly differentiated pelvic synovial sarcoma with molecular
      confirmation: a rare presentation of an uncommon disease entity.
AB  - Pelvic localization of synovial sarcoma is a rare phenomenon and to the best of
      our knowledge its presentation as a large "dumb-bell"-shaped abdomino-pelvic mass
      showing extension to the thigh has never been reported in the literature. We
      report a case of a young adult presenting with retention of urine and was found
      to have a large abdomino-pelvic mass causing bony destruction and compression of
      pelvic viscera. A biopsy revealed a cellular tumor composed of spindle to oval
      cells arranged in a hemangiopericytomatous pattern. Histopathology was suggestive
      of poorly differentiated synovial sarcoma. Immunohistochemistry (IHC) was
      positive for vimentin, CD 99, Bcl2, Mic2 and focally for EMA and negative for CD
      34, CK, desmin, synaptophysin, and WT1. Due to equivocal IHC findings molecular
      analysis was done which confirmed the diagnosis as synovial sarcoma. 

PMID- 24441230
TI  - Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular
      variant of papillary carcinoma of the thyroid.
AB  - Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular
      variant of papillary carcinoma is described in the same thyroid, with study of
      p53 expression. A 72-year-old woman presented to the endocrinology out-patient
      unit for a routine follow-up visit. Patient underwent a total thyroidectomy.
      Histological examination revealed a solid nodular neoplasm with the longest
      diameter of 0.8 cm in the upper pole of the left lobe. The neoplasm showed the
      histological features of follicular variant of papillary carcinoma with moderate
      diffuse immunoreactivity for p53. The lower pole of the right lobe showed two
      adjacent nodules with histological features respectively of atypical adenoma and
      adenoma with bizarre nuclei, with strong diffuse immunoreactivity for p53. 

PMID- 24441231
TI  - Desmin-related restrictive cardiomyopathy in a pediatric patient: a case report.
AB  - Restrictive cardiomyopathies in the pediatric population have diverse etiologies,
      including storage diseases like hemosiderosis, glycogenoses and desmin with its
      associated proteins. Desmin-related myopathy is a rare familial disorder of the
      cardiac and skeletal muscle characterized by intrasarcoplasmic accumulation of
      desmin-reactive deposits in the muscle cells. The patients commonly present with
      cardiac involvement such as conduction blocks and/or restrictive cardiomyopathy.
      Diagnosis of desmin cardiomyopathy depends on light microscopic evaluation of
      endomyocardial biopsy, where abnormal deposition of desmin can be documented on
      immunohistochemistry and ultrastructural examination. The index report presents
      the clinical, light microscopic and ultrastructural findings of desmin
      cardiomyopathy. 

PMID- 24441232
TI  - Angiolymphoid hyperplasia with eosinophilia: a rare benign vascular tumor of
      breast.
AB  - Angiolymphoid hyperplasia with eosinophilia typically involves head and neck with
      rare involvement of other sites like breast. A 27year old female presented with a
      painless swelling in the upper and outer quadrant of left breast. Fine needle
      aspiration cytology showed sheets of lymphoid cells along with numerous
      eosinophils. Subsequent histopathological examination showed eosinophilic plump
      and vacuolated endothelial cells in small groups and sheets within a fibrous
      background, typically accompanied by lymphoid aggregates and eosinophils,
      suggestive of angiolymphoid hyperplasia with eosinophilia. Vascular tumors of the
      breast are extremely rare. The goal of this case report is to advert to this
      unusual clinical picture, to review and discuss diagnostics, differential
      diagnoses and treatment options. 

PMID- 24441233
TI  - Sebaceous carcinoma with apocrine differentiation: a rare entity with aggressive
      behavior.
AB  - Sebaceous carcinomas are rare neoplasms but have aggressive behavior. Although
      they can be found anywhere in the body ocular region is the most common site
      which comprises 75% of all cases of sebaceous carcinomas. Due to their rarity,
      varied histopathological features, and diverse clinical presentation, their
      diagnosis is often delayed, sometimes by a year. They are divided on the basis of
      histological differentiation into well and poorly differentiated. Apocrine
      differentiation is a still rarer finding and only two cases have been reported in
      the literature so far. We report a case of sebaceous carcinoma with apocrine
      differentiation in a 60-year-old male who presented with a painless swelling in
      right upper eyelid for 2 months which was gradually progressive. Computed
      tomography (CT) scan was performed and a provisional diagnosis of hemangioma was
      made. The mass was excised and histopathological examination revealed it to be
      sebaceous carcinoma. However, there were areas with decapitation secretions and
      granular eosinophilic cytoplasm. These were positive for cytokeratin (CK) 7 and
      CK 19 which confirmed their apocrine nature. Therefore, a final diagnosis of
      sebaceous carcinoma with apocrine differentiation was made. Thus, it can be
      concluded that ocular sebaceous carcinomas with apocrine differentiation are
      extremely rare and have significant clinical importance since they can mimic a
      benign lesion and the nature of surgical intervention and follow up is more
      aggressive than that of simple sebaceous carcinoma alone. 

PMID- 24441234
TI  - Perianal bronchogenic cyst: a report of two cases.
AB  - Cutaneous presentations of bronchogenic cysts are rare in all age groups,
      particularly in adults. Previous reports showed that cutaneous manifestations of
      bronchogenic cysts were frequently presented above abdominal region. Here we
      present two cases of a perianal bronchogenic cyst. To the best to our knowledge,
      this is the first report of a bronchogenic cyst in this area. 

PMID- 24441235
TI  - Benign signet ring cells in pseudomembranous colitis: a diagnostic trap.
AB  - A 71-year-old female patient was admitted with intractable diarrhea and abdominal
      distention following several courses of broad spectrum antibiotic therapy.
      Colonic biopsy revealed pseudomembranous colitis with foci of signet ring cell
      (SRC) change. The SRCs possessed bland nuclei and were confined to the basement
      membranes of the crypts with no infiltration into the lamina propria. Benign SRCs
      in pseudomembranous colitis is an uncommon phenomenon. Awareness of this rare,
      but potential pitfall is of utmost importance to avoid a misdiagnosis of SRC
      carcinoma. 

PMID- 24441236
TI  - Primary gastric adenosquamous carcinoma in an Indian male.
AB  - Adenosquamous carcinoma (ASC) of the stomach is a very rare tumor comprising less
      than 0.5% of all stomach malignancies. Here, we report a case of a 37-year-old
      male, who presented with upper gastrointestinal bleeding in the form of
      hematemesis and malena. A subtotal gastrectomy was done in view of massive
      uncontrolled bleed. Histology showed evidence of ASC of the body and antrum with
      metastasis to the liver, perigastric lymph nodes and peritoneal and pleural
      cavity. 

PMID- 24441237
TI  - Primary subcutaneous mixed-type liposarcoma of the thigh showing three
      simultaneous dedifferentiations: report of an unusual case.
AB  - Liposarcoma most commonly occurs in deep soft tissues of the limb and the
      retroperitoneum; however, its occurrence in the subcutaneous tissue is rare.
      Mixed-type liposarcoma (MTL) is the rarest subtype. We herein describe a unique
      case of MTL with three simultaneous dedifferentiations occurring in subcutaneous
      tissue of left thigh in a 45-year-old male. We briefly review the pertinent
      literature and report this case because of extreme rarity. 

PMID- 24441238
TI  - Epithelioid hemangioma of the testis.
AB  - Testicular hemangioma is a very rare benign vascular neoplasm, there are only
      less than 30 cases of testicular hemangiomas reported in the literature. We
      report a case of epithelioid hemangioma of the testis in a 53-year-old man who
      presented with painless mass in the right testis. An orchiectomy was performed,
      The 1 cm tumor was composed of prominent proliferation of small, capillary-sized
      vessels lined by plump, epithelioid endothelial cells. Immunohistochemically, the
      epithelioid endothelial cells reacted with antibodies to factor VIII-related
      antigen, CD31, CD34 and Vimentin, but not CK, EMA, CEA, S-100 and CD68. Although
      it is a rare tumor, we should be aware of it and avoid confusion with other
      vascular neoplasm. 

PMID- 24441239
TI  - Primary intratesticular pleomorphic leiomyosarcoma: a rare case report.
AB  - Intratesticular leiomyosarcoma is an extremely rare tumor of the genitourinary
      system. We report a case of intratesticular pleomorphic leiomyosarcoma in a 68
      year-old male who presented with gradual painless enlargement of the right
      scrotal mass over a period of 1-2 years. Radiological examination revealed a
      right testicular tumor.Right radical orchiectomy was performed with high ligation
      of the spermatic cord. Histopathological examination along with
      immunohistochemistry confirmed the diagnosis of a pleomorphic leiomyosarcoma of
      the testis. This is, to the best of our knowledge, the 13 th case of primary
      intratesticular leiomyosarcoma and the third case of high-grade (pleomorphic)
      intratesticular leiomyosarcoma in an elderly male reported in the literature. 

PMID- 24441240
TI  - Novel molecular aberrations and pathologic findings in a tubulocystic variant of
      renal cell carcinoma.
AB  - Tubulocystic renal cell carcinoma (TRCC) is an indolent type of renal cell
      carcinoma with a good prognosis based on the limited number of published cases.
      Herein, we describe the unusual clinical, pathologic and molecular findings in a
      case of TRCC. Our patient with TRCC had two local recurrences and a brain
      metastasis following radical nephrectomy. Unusual histologic findings included
      focal solid growth pattern and cytologic atypia. A genome-wide molecular
      inversion probe assay identified copy number (CN) loss in three chromosome
      regions and one region with copy-neutral loss of heterozygosity (copy-neutral
      LOH). Copy number variations (CNVs) were observed (chromosomes 4p16.1 and
      17q21.31-q21.32) in both the tumor and the normal tissue, and most likely
      represents benign variations. The loss of entire chromosomes 9, 18 and 15 and
      copy-neutral LOH involving 6p22.1 was observed only in the tumor. The presence of
      these clinical, pathologic and molecular findings could be related to an
      increased risk for tumor recurrence and poor prognosis. The novel molecular
      findings described in TRCC might represent new targets for novel therapies. 

PMID- 24441241
TI  - Immunohistochemical analyses of a case of extralobar pulmonary sequestration with
      chest pain in an adult.
AB  - Computed tomography of a Japanese man in his mid-forties with a complaint of
      right-side chest pain showed a dome-shaped smooth-surfaced mediastinal mass,
      which was extirpated. The cut surface was highly hemorrhagic and necrotic and not
      related to the original pulmonary tissues. Although routine sectioning detected
      bronchial cartilage, immunohistochemical analyses clearly showed the presence of
      alveolar type II cells; only the alveolar type II cells located at the periphery
      of this mass showed positive staining for cytokeratins, thyroid transcription
      factor 1, surfactant protein A, epithelial membrane antigen and Krebs von den
      Lungen-6. Thus, these analyses are useful for the detection of pulmonary
      components, even in severely hemorrhagic and necrotic tissues with marked
      sequestration. The clinical diagnosis was a rare, adult type of extralobar
      pulmonary sequestration accompanied by chest pain. 

PMID- 24441242
TI  - Cystic panfolliculoma of the scalp: report of a very rare case and brief review.
AB  - Panfolliculoma is an exceeding rare follicular benign neoplasm with
      differentiation toward both upper and lower segments of the hair follicle. In
      this report, we present a case of cystic panfolliculoma in the occipital region
      of the scalp of a 19-year-old female. We describe the histopathological and
      immunohistochemical features of the tumor and briefly discuss the differential
      diagnoses of this rare entity. 

PMID- 24441243
TI  - Nodular lymphocyte predominant Hodgkin lymphoma and diphenylhydantoin: report of
      a case and review of the literature.
AB  - A variety of lymphoma types have been reported in patients being treated with
      anticonvulsant therapy. Non-Hodgkin lymphomas have been reported twice as
      frequently as Hodgkin lymphomas. Association of nodular lymphocyte predominant
      Hodgkin lymphoma (NLPHL) with dilantin therapy is extremely uncommon. We report a
      case of Hodgkin lymphoma in a 25-year-old male patient who had been treated with
      diphenylhydantoin sodium for generalized tonic clonic seizures for 15 years.
      Patient presented with left cervical and axillary lymphadenopathy persisting for
      more than 2 years after cessation of treatment with diphenylhydantoin.
      Computerized tomography scan of thorax, abdomen and pelvis revealed no
      significant lymphadenopathy or any organomegaly. Diagnosis of NLPHL was made on
      excision biopsy of the cervical lymph node. Although the association between
      diphenylhydantoin therapy and the development of immunosuppression and lymphoma
      is well-documented, the role of the drug in the etiology of these disorders is
      still controversial. 

PMID- 24441244
TI  - Isolated malakoplakia of inguinal lymph node: a rare case report.
AB  - Malakoplakia is rare chronic inflammatory disorder which commonly affects urinary
      tract. Though it has been reported in several sites outside the urinary tract,
      isolated lympnode involvement is extremely uncommon. Herein we present a case of
      20 year old male with right inguinal lymphnodal mass. Histological findings
      including special stains and immunohistochemistry findings were characteristic of
      malakoplakia. This case is being presented to create awareness for inclusion of
      this entity in the differential diagnosis of lymphadenopathy. 

PMID- 24441245
TI  - T-lineage acute lymphoblastic leukemia and parvovirus infection in a child with
      neurofibromastosis-1.
AB  - Neurofibromatosis (NF-1) patients have an increased risk of developing
      malignancies most commonly rhabdomyosarcomas, optic gliomas, brain tumors and non
      lymphocytic leukemias. Acute lymphoblastic leukemia (ALL) has been infrequently
      reported in association with NF-1. We describe a rare association of NF-1, T
      lineage ALL and parvovirus infection in a 12-year-old child. In addition, it is
      also to emphasize that a high index of suspicion should be kept for parvovirus
      B19 infection as a cause of bicytopenia/pancytopenia in ALL patients following
      induction chemotherapy. 

PMID- 24441246
TI  - Diffuse large B-cell lymphoma of the kidney: a rare neoplasm.
AB  - Primary renal lymphoma is a rare neoplasm, but it should be kept in mind in the
      differential diagnosis of renal neoplasms. A middle aged man presented with
      symptoms of weight loss, anorexia and fullness of the abdomen after meals. On
      clinical and radiological examination, a renal mass was revealed and operated
      upon. A diagnosis of primary high grade renal lymphoma was made on
      histopathological examination and immunohistochemically it was further classified
      as diffuse large B-cell lymphoma. Unfortunately, the patient died after 5 months
      of diagnosis in spite of three cycles of chemotherapy following surgery. The
      pathological details of rare tumor are presented here. 

PMID- 24441247
TI  - Simultaneous occurrence of chronic myeloid leukemia and chronic lymphocytic
      leukemia: report of an unusual case.
AB  - The coexistence of chronic myeloid leukaemia(CML) and chronic lymphocytic
      leukemia(CLL) has been reported occasionally in literature, with only seven cases
      of simultaneous occurrence of these two diseases. We present here a case of 57 yr
      male patient where a complete blood count and differential done using volume
      conductivity scatter (VCS) technology suggested a diagnosis of CML with CLL. It
      was further confirmed by immunophneotyping and cytogenetic analysis. The patient
      was started on tyrosine kinase inhibitor, 400 mg once daily. Four months after
      the treatment, patient is doing fine with a count of 22 * 10 9 /L and 64%
      lymphocytes. 

PMID- 24441248
TI  - Co-infection of Mycoplasma genitalium and Chlamydia trachomatis in an infertile
      female patient with genital tuberculosis.
AB  - Genital tuberculosis is a common cause of female infertility in India. But, it is
      important to screen for other agents like Chlamydia trachomatis and genital
      Mycoplasmas as well to avoid persistence of infection and its long-term sequelae.
      Timely diagnosis of these infections using nucleic acid amplification tests and
      institution of appropriate therapy will improve the conception rates in infertile
      women. We report a case of co-infection of Mycoplasma genitalium and Chlamydia
      trachomatis in an infertile female patient with genital tuberculosis. The
      infections were diagnosed using polymerase chain reaction, and the patient
      responded to a combination of antituberculosis therapy and 1 g single-dose
      Azithromycin. 

PMID- 24441249
TI  - Chronic suppurative joint effusion due to burkholderia pseudomallei: a case
      report.
AB  - Burkholderia pseudomallei, a Gram-negative bacillus is the causative agent of
      Melioidosis, a glanders-like disease, primarily a disease of animals. Melioidosis
      has been only a rare and sporadic disease in humans outside its endemic region.
      Currently, diagnosis of B. pseudomallei in the clinical laboratory is very
      difficult, owing to low awareness of physicians to the nonspecific clinical
      manifestations, lack of responsiveness among microbiologists outside endemic
      areas, identification systems in the average sentinel laboratory, and the
      biosafety conditions necessary to process these organisms. We report a case of
      chronic left hip joint effusion in a known case of diabetes mellitus. Gram stain
      of computed tomography (CT)-guided aspirate from the joint revealed Gram-negative
      bacilli along with pus cells. Culture was confirmed as Burkholderia pseudomallei
      on Vitek2C, which was sensitive to ceftazidime and trimethoprim/sulfmethoxazole.
      Unfortunately, patient could not be started on appropriate antibiotics due to
      delay in detection and patient succumbed to severe septicemia. This case is
      reported to highlight importance of automated identification and sensitivity
      especially in nonendemic areas and unusual antibiogram of this organism for which
      disc diffusion method is not standardized. 

PMID- 24441250
TI  - Chondroid lipoma of the thigh: a case report.
AB  - Chondroid lipoma is an unusual, unique benign lipomatous tumor. We present a case
      of chondroid lipoma of right thigh in 46-year- old female to highlight the
      distinct morphological simily, it is important to distinguish it from
      extraskeletal chondrosarcoma and myxoid liposarcoma. The review of the literature
      has been discussed. 

PMID- 24441251
TI  - Isolated eccentric lingual diphtheria: a relevance.

PMID- 24441252
TI  - Lipid lymphadenopathy.

PMID- 24441253
TI  - Extensively calcified cystic extraventricular neurocytoma.

PMID- 24441254
TI  - Xp11 translocation renal cell carcinoma.

PMID- 24441255
TI  - Multiple lymphoepithelial cysts from oral mucosa of a healthy woman: case report
      and literature review.

PMID- 24441256
TI  - Splenogonadal fusion: pathological features of a rare scrotal mass.

PMID- 24441257
TI  - Pleural multicystic mesothelial proliferation: a mimicker of benign peritoneal
      mesothelioma.

PMID- 24441258
TI  - Epibulbar dermolipoma.

PMID- 24441259
TI  - Primary primitive neuroectodermal tumor of lung: a case report.

PMID- 24441260
TI  - Tuberculosis of the parapharyngeal space: a rare case report.

PMID- 24441261
TI  - A case of multi-drug-resistant, intracranial tuberculomas, presenting with
      headache.

PMID- 24441262
TI  - Limitation of HPLC methodology for HBA1c estimation.

PMID- 24441263
TI  - Antibiogram of Salmonella typhi and Salmonella paratyphi A in a tertiary care
      hospital in 2012.

PMID- 24441264
TI  - Utility of Cysteine lactose electrolyte-deficient agar for rapid isolation of
      Nocardia species.

PMID- 24441265
TI  - Towards imaging electron density inside metal-organic framework structures.
AB  - Herein, we present electron density maps of three MOFs with different guests or
      post-synthetic modifications produced using single crystal X-ray data from
      laboratory diffractometers. Analysis of the electron density maps reveals
      possible differences inside the pores indicating that this approach may be used
      to explore frameworks using inexpensively gained X-ray data. 

PMID- 24441266
TI  - Single-process versus multiple-strategy models of decision making: evidence from
      an information intrusion paradigm.
AB  - When decision makers are confronted with different problems and situations, do
      they use a uniform mechanism as assumed by single-process models (SPMs) or do
      they choose adaptively from a set of available decision strategies as multiple
      strategy models (MSMs) imply? Both frameworks of decision making have gathered a
      lot of support, but only rarely have they been contrasted with each other.
      Employing an information intrusion paradigm for multi-attribute decisions from
      givens, SPM and MSM predictions on information search, decision outcomes,
      attention, and confidence judgments were derived and tested against each other in
      two experiments. The results consistently support the SPM view: Participants
      seemingly using a "take-the-best" (TTB) strategy do not ignore TTB-irrelevant
      information as MSMs would predict, but adapt the amount of information searched,
      choose alternative choice options, and show varying confidence judgments
      contingent on the quality of the "irrelevant" information. The uniformity of
      these findings underlines the adequacy of the novel information intrusion
      paradigm and comprehensively promotes the notion of a uniform decision making
      mechanism as assumed by single-process models. 

PMID- 24441267
TI  - From the editor.

PMID- 24441268
TI  - The transfer of knowledge in occupational therapy: the case of work ability
      assessment.
AB  - Kunskapsoverforingen inom arbetsterapi diskuteras i marknadsforingstermer. Dessa
      exemplifieras med strategier som forfattarna foreslar for att larare, kliniskt
      verksamma arbetsterapeuter och annan rehabiliteringspersonal skulle kunna
      forbattra sina kunskaper om arbetsformagebedomningar och om arbetsrelsterade
      rehabiliteringsprogram. 

PMID- 24441269
TI  - The nature of work. An idea to a curriculum of work.
AB  - Studien handlar om arbetets natur utifran ett nationellt och ett internationellt
      synsatt. Arbetets natur ar fullt av nyanser och denna studie vill pavisa detta
      for lasaren. Studien innehaller slutligen aven en ide till en studiehandledning i
      Arbete. Detta forslag till studiehandledning i Arbete galler for
      arbetsterapeututbildningen pa Halsohogskolan i Stockholm. 

PMID- 24441270
TI  - Work technique training for patients with chronic pain in neck, shoulder and arm.
      A questionnaire pilot study after a comprehensive exercise-oriented
      rehabilitation program.
AB  - Syftet med denna studie var att folja upp hur patienter sag pa sin arbetsmiljo
      och arbetsteknik samt hur foreslagna arbetsplatsanpassningar hade genomforts
      efter deltagande i ett multimodalt intensivtraningsinriktat
      rehabiliteringsprogram. Programmet inkluderade en vasentlig del av individuell
      ergonomisk analys, individuell ergonomisk radgivning och specifik
      arbeetstekniktraning pa arbetsterapiavdelningen. Patienterna hade kronisk
      muskuloskelettal smarta i armen. Efter rehabiliteringsprogrammet skickades ett
      frageformular till 181 patienter, varav 135 patienter (109 kvinnor och 26 man)
      (75%) svarade. Mer an halften av patienterna rapporterade att de oftere an en
      gang i veckan tankte tillbaka pa den individuella ergonomiska radgivningen som
      gavs i samband med att videofilmen tagen pa deras arbetsplats presenterades.
      Deras skattningar visade pa en hog medvetandegrad nar det gallde att la
      mikropauser under arbetet (dvs atl rata upp ryggen kombinerat med
      muskelavslappning), att arbeta med armarna nara kroppen och att lyfta bordor nara
      kroppen. Halften av patienterna hade anvant sig av mojligheten att andra
      arbetsstallning mer an en gang per timme. Resultatet indikerar att patienterna
      var medvetna om sin arbetsteknik efter deltagandet i rehabiliteringsprogrammet. 

PMID- 24441271
TI  - How children with mental retardation in Swedish schools are prepared for work in
      adult life.
AB  - Utvecklingsstorda barn i Sverige gar i sarskola. I denna artikel undersoks hur
      dessa elever forbereds for arbete i vuxen alder utifran Maurer's modell om
      vocational development genom att studera gallande laroplaner. Resultatet
      indikerar att i laroplanerna beaktas de olika faserna i vocational development.
      Anda ar fa utvecklingsstorda anstallda pa oppna arbetsmarknaden. Orsaker till
      detta diskuteras. 

PMID- 24441272
TI  - Tool design in relation to hand function: course content for occupational
      therapists.
AB  - Arbetsterapeuten moter i sin yrkesutovning personer som har svarigheter att
      anvanda sina hander i vardagliga aktiviteter. Det kan vara svarighet eller
      forlust av formagan att halla i och arbeta med verktyg, av olika slag. Verktygens
      utformning kan vara orsak till funktionsnedsattningen. Kunskap om handens
      funktion och ergonomiska aspekter pa verktygens utformning ar viktig kunskap for
      arbetsterapeuter.I artikeln presenteras en kunskapsgrund, som anvads i
      grundutbildningen av arbetsterapeuter i Sverige. 

PMID- 24441273
TI  - Vocational rehabilitation within the labour market administration in Sweden.
AB  - I den yrkesinriktade rehabiliteringen tillampar arbetsterapeuten sina kunskaper
      inom omradet "arbete" mot bakgrunden av klientens hela livssituation och i
      samverkan med ovriga specialister inom omradet. Grunduppgiften for
      arbetsmarknadsinstituten ar att medverka till att arbetssokande som ar radvilla
      eller har en nedsatt/begransad arbetsformaga, skall finna, fa och behalla ett
      arbete som ar sa val anpassat for den arbetssokandes personliga forutsattningar
      som mojligt.Den praktiska provnings och traningsenheten (Praot) bedrivs i syfte
      att genom praktisk provning/traning och intressevackande uppgifter gora
      funktionsbedomningar och bedomning av arbetsformaga. De sokande far hjalp att i
      en praktisk arbetssituation se sina resurser och hur dessa kan anvandas pa
      arbetsmarknaden. Har kan aven arbetssokandes ev, arbetshjalpmedel tranas in att
      anvandas. 

PMID- 24441274
TI  - Vocational rehabilitation: a Swedish model for assessment, treatment, training
      and reinstatement.
AB  - Det som karaktariserar den yrkesinriktade rehabiliteringen i Sverige ar
      samarbetet mellan den rehabilitering som bedrivs inom sjukvarden och de
      yrkesinriktade atgarder som Arbetsformedling. Arbetsmarknadsinstitut och
      Forsakringskassa kan erbjuda. Dessa senare institutioner ansvarar for praktiska
      rehabiliteringsinsatser och ekonomisk ersattning till langtidssjukskrivna eller
      arbetslosa. Okad arbetsloshet staller hogre krav pa samarbete och
      rehabiliteringens utformning. Rehabiliteringsmedicinska kliniken vid Karolinska
      sjukhuset forandrar darfor sina rutiner i syfte att battre svara mot de okande
      kraven. 

PMID- 24441275
TI  - Ergonomic and technical evaluation of an eye-controlled computer with 'eyegaze'.
AB  - Datortekniken oppnar nya vagar och mojligheter for personer med grava
      rorelsehandikapp. Eyegaze ar ett avancerat hjalpmedel som innebar att man kan
      styra en dator med ogonrorelser. Personer med mycket begransad rorlighet har i
      studien fatt jamfora att styra dator med ogonrorelser (EYEGAZE) med att styra
      dator med huvudmus. Eyegaze upplevs som fysiskt lattare men uppvisar hogre grad
      av statisk muskelbelastning. Att arbeta med Eyegaze kraver individuell
      anpassning, hog uppmarksamhetsgrad och en avskild, lugn arbetsplats. Tekniskt
      sett har Eyegaze i dagslaget en nagot begransad anvandbarhet da programvaran ar
      textbaserad och kraver stort utrymme i datoms intemminne. 

PMID- 24441276
TI  - Swedish use and validation of Valpar work samples for patients with
      musculoskeletal neck and shoulder pain.
AB  - I studien beskrivs vad e bedomning av arbetskapacitet (BAK) innehaller Vid en
      bedomning av arbetskapacitet jamfors kraven for att utfora ett specifikt arbete,
      definierat i "The dictionary of Occupational Titles" (DOT), och patientens
      formaga att utfora ett arbote vilket definieras med hjalp av sju variabler.
      Allman utbildnings niva. Speciella yrkesforberedelser. Anlag, Intresseomraden,
      Personlig laggning. Fysiska drav och Miljopaverkan. En bedomning av
      arbetskapaciteten kan ske antingen genom att observera patienten under arbete
      paarbetsplatsen eller under simulerat arbete tex genom att anvanda Valpar
      systemets arbetsprover.Vid Rehabiliteringsmedicinska kliniken, Karolinska
      Sjukhuset har tva av de standardiserade arbetsprovema anvants. VCWS 8 "Simulerad
      moontering" och VCWS 9 "Simulerade rorelser for hela kroppen" for att forbattra
      bedomningen av patientens arbetskapacitet. VCWS 8 mater "en persons formaga att
      utfora ett monteringsarbete som kraver repetetiva fysiska manipulationer" och
      VCWS 9 mater "en persons formaga att rora pa balen, nacken, armarna, handerna och
      fingrama nar de relaterar till funktionellt utforande av ett arbete".
      Valideringen av arbetsprovema for Svensk anvandning gjordes pa en grupp patienter
      (n = 97) med muskuloskelettal nack- och skulder smarta som deltog i ett
      rehabiliteringsprogram. VCWS 9 utfordes av attiofem patienter och VCWS 9 av
      sextionic patienter.Medelvardet for patienterna som slutforde VCWS 8 var 83.1% av
      industriell standard niva (matt enligt MTM-Method-Time-Measurement) dar den la
      gsta gransen ar 87.5% for ett godkannt utforende. Detta innebar att de "inte
      moter" kraven for detta specifika arbete. I motsats till detta sa nadde
      patientema som utforde VCWS 9 ett medelvarde pa 108.6% vilket overstiger kravet
      (87.5%) for industriell standard. Det ovantade resultatet kan kanske forklaras av
      att patienternas intresseomraden vad galler arbetsfalt endast sammanfoll med
      iintresseomradena for VCWS 8 och yeWS 9 i 32% av fallen. En retrospective
      jamforelse mellan att vara sjukskriven eller inte vara sjukskriven och deras
      formaga att utfora ett arbetsprov och uppna minimi kravet for industriell
      standard visade inte pa nagot samband. Manga faktorer kan ha paverkat resultatet
      som tex patientens motivation, andra psyko-sociala omstandigheter och
      arbetsterapeutemas beslut att endast anvanda sig av tva stycken av ett flertal
      arbetsprov.Konklusiionen ar att en bedorning av patientens arbetskapacitet skall
      utforas prospektivt och bor ta i beraknng de krav arbetet staller enligt DOT och
      darefter bor ratt arbetsprov vaijas for den individuella patienten. Sker detta pa
      ett riktigt satt sa ar Valpars arbetsprover valida och till stor hjalp vid en
      medicinsk bedomning och for beslut nar det galler fortsatt sjukskrivning eller
      vid yrkesradgivning. 

PMID- 24441277
TI  - A view from the USA.

PMID- 24441279
TI  - Effect of deltamethrin (pyrethroid insecticide) on two clones of Daphnia magna
      (Crustacea, Cladocera): a proteomic investigation.
AB  - Deltamethrin is a class II pyrethroid insecticide commonly used in agriculture.
      It is hazardous to freshwater ecosystems, especially for the cladoceran Daphnia
      magna (Straus 1820). The results of our previous studies based on acute and
      chronic ecotoxicity experiments revealed differences in the sensitivity between
      two different clones. In this work, to investigate deltamethrin toxicity
      mechanisms in two clones of D. magna, we used a proteomic approach in order to
      analyze changes in protein expression profiles after 48 h of exposure. We
      detected 1339 spots; then applying statistical criteria (ANOVA p<0.001 and
      minimum fold change 1.5), only 128 spots were significantly different in the
      normalized volume. Among the preselected proteins there were 88 up-regulated and
      40 down-regulated proteins. Results showed differences in sensitivities after
      deltamethrin exposure between the clones. Moreover, using the 2-DIGE method,
      proteomic investigation for deltamethrin exposure proved to be a reliable and
      powerful approach to investigate effects of deltamethrin as part of research for
      new metabolic and cellular biomarkers. After identification by mass spectrometry,
      there were 39 proteins recognized and identified, in which 21 and 18 were up- and
      down-regulated, respectively, in deltamethrin-exposed clone A compared to three
      other conditions (controls of each clone and deltamethrin-exposed clone 2). Up-
      and down-regulated proteins belonged to 12 biological processes (i.e. metabolic
      processes, apoptosis and stimulus response) and 5 molecular functions (i.e.
      catalytic activity, binding, structural molecular activity, antioxidant and
      receptor activities). Identification of these deregulated proteins opens a new
      way in discovering new molecular targets and putative biomarkers in daphnids
      exposed to deltamethrin.

PMID- 24441280
TI  - Sandy sediment and the bioavailability of 17beta-trenbolone to adult female
      fathead minnows.
AB  - Recent studies have detected bioavailable steroids in sediment, however, the
      mechanism by which these compounds become bioavailable is not completely
      understood. In this study, two experiments were conducted using a double aquarium
      system that allowed female fathead minnows to be exposed to sandy sediments
      without direct contact. In the first experiment, natural sediment from the
      Elkhorn River (Nebraska, USA) was spiked with 17beta-trenbolone. Both the fish in
      direct contact with the sediment as well as the fish excluded from direct contact
      experienced significant reductions in the hepatic expression of two estrogen
      responsive genes, vitellogenin and estrogen receptor alpha, indicating molecular
      defeminization. The natural sediment contained particles ranging in size from
      sand to clay and it was possible that the fish in experiment 1 were being exposed
      to trenbolone associated with the very fine particles. The sandy sediment was
      sieved for experiment 2, and only the particles larger than 250 MUm were used. In
      addition, the experiment was conducted at two different Tb concentrations (1* and
      10*). Furthermore nuptial tubercles, a biomarker of exposure to a masculinizing
      androgen, were also evaluated in the females used in experiment 2. For tubercle
      number and vtg expression, significant results were obtained from a two-way ANOVA
      due to Tb concentration, but not tank location or interaction term (location vs.
      concentration). For ERalpha expression, results were found in response to Tb
      concentration and tank location, but not the interaction term. Overall the
      results from these studies suggest that the primary route of exposure of sediment
      associated trenbolone to fish is through ventilation of free compound, rather
      than ingestion or direct contact with the sediments.

PMID- 24441282
TI  - Ferrocenyl-phosphonium ionic liquids - synthesis, characterisation and
      electrochemistry.
AB  - New unsymmetrically substituted ferrocenyl-phosphonium ionic liquids (ILs)
      [FcPR2R']NTf2 are synthesized by two or three step syntheses starting from
      ferrocene, Fc = (C5H5)Fe(C5H4); R = Me, (n)Bu, (n)Hex, Ph; R' = Me, (n)Pr, (n)Bu,
      Ph; NTf2 = N(SO2CF3)2. The selective synthesis of alkyl phosphines FcPR2via a
      Friedel-Crafts phosphorylation is highlighted as an alternative for the standard
      protocol commonly used for ferrocenyl arylphosphines involving lithiation of FcH
      followed by phosphorylation. The influence of the P-substituents on thermal
      stability, electrochemical potential, chemical shift, and UV-Vis absorption
      behavior of the ILs is studied. The phosphonium group acts both as an ionic tag
      and as an electron-withdrawing substituent directly bound at the Cp-ring
      position. Therefore the title compounds are attractive for further studies to use
      them as tunable redox mediators for (photo)electrochemical devices such as dye
      sensitized solar cells (DSSCs) or redox flow batteries. 

PMID- 24441281
TI  - Advances in small bowel neuroendocrine neoplasia.
AB  - PURPOSE OF REVIEW: This review aims at summarizing progress in clinical trials
      and basic science redefining the diagnosis and treatment of well differentiated
      small intestine neuroendocrine tumors (SI-NET). RECENT FINDINGS: Two clinical
      trials demonstrated antitumor activity of the long-acting somatostatin analogues
      octreotide long-acting release and lanreotide for advanced SI-NET. The mammalian
      target of rapamycin (mTOR) inhibitor everolimus is another treatment option for
      patients with SI-NET, but awaits definitive proof of benefit in the ongoing
      RAD001 In Advanced Neuroendocrine Tumors study (RADIANT-4). Two whole
      exome/genome-sequencing studies reported in the past year provided the first
      genome-wide analysis of large sets of SI-NET at nucleotide resolution. Candidate
      therapeutically relevant alterations were found to affect SRC, SMAD genes, aurora
      kinase A, epidermal growth factor receptor, heat shock protein 90, and platelet
      derived growth factor receptor as well as mutually exclusive amplification of RAC
      alpha serine/threonine-protein kinase (AKT1) or AKT2 and other alterations of
      PI3K/Akt/mTOR signaling genes. The gene CDKN1B is inactivated by small
      insertions/deletions in 8% of patients with SI-NET suggesting cell cycle
      inhibitors as new candidate drugs for SI-NET. Circulating tumor cells and tumor
      derived RNA in the blood are promising clinical tests for SI-NET. SUMMARY:
      Clinical and genomic research may merge in the near future to re-shape clinical
      trials and to define the 'personalized' treatment options for patients with SI
      NET.

PMID- 24441283
TI  - Fine-scale nutrient and carbonate system dynamics around cold-water coral reefs
      in the northeast Atlantic.
AB  - Ocean acidification has been suggested as a serious threat to the future
      existence of cold-water corals (CWC). However, there are few fine-scale temporal
      and spatial datasets of carbonate and nutrients conditions available for these
      reefs, which can provide a baseline definition of extant conditions. Here we
      provide observational data from four different sites in the northeast Atlantic
      that are known habitats for CWC. These habitats differ by depth and by the nature
      of the coral habitat. At depths where CWC are known to occur across these sites
      the dissolved inorganic carbon ranged from 2088 to 2186 MUmol kg(-1), alkalinity
      ranged from 2299 to 2346 MUmol kg(-1), and aragonite Omega ranged from 1.35 to
      2.44. At two sites fine-scale hydrodynamics caused increased variability in the
      carbonate and nutrient conditions over daily time-scales. The observed high level
      of variability must be taken into account when assessing CWC sensitivities to
      future environmental change. 

PMID- 24441284
TI  - Boosting health insurance coverage in developing countries: do conditional cash
      transfer programmes matter in Mexico?
AB  - BACKGROUND: Achieving universal health insurance coverage is a goal for many
      developing countries. Even when universal health insurance programmes are in
      place, there are significant barriers to reaching the lowest socio-economic
      groups such as a lack of awareness of the programmes or knowledge of the benefits
      to participating in the insurance market. Conditional cash transfer (CCT)
      programmes can encourage participation through mandatory health education
      classes, increased contact with the health care system and cash payments to
      reduce costs of participating in the insurance market. OBJECTIVE: To explore if
      participation in a CCT programme in Mexico, Oportunidades, is significantly
      associated with self-reported enrolment in a public health insurance programme.
      METHODS: Cross-sectional data from 2007 collected on 29 595 Mexican households
      where the household head is aged between ages 15 and 60 were analysed. A logit
      model was used to estimate the association between Oportunidades participation
      and awareness of enrolment in a public health insurance programme. RESULTS:
      Participation in the Oportunidades programme is associated with a 25% higher
      likelihood of being actively aware of enrolment in Seguro Popular, a public
      health insurance scheme for the lowest socio-economic groups. CONCLUSIONS:
      Participation in the Oportunidades CCT programme is positively associated with
      awareness of enrolment in public health insurance. CCT programmes may be used to
      promote participation of the lowest socio-economic groups in universal public
      health insurance systems. This is crucial to achieving universal health insurance
      coverage in developing countries.

PMID- 24441286
TI  - The clinical significance of ABCC3 as an imatinib transporter in chronic myeloid
      leukaemia.

PMID- 24441285
TI  - Radiogenomics: using genetics to identify cancer patients at risk for development
      of adverse effects following radiotherapy.
AB  - Normal-tissue adverse effects following radiotherapy are common and significantly
      affect quality of life. These effects cannot be accounted for by dosimetric,
      treatment, or demographic factors alone, and evidence suggests that common
      genetic variants are associated with radiotherapy adverse effects. The field of
      radiogenomics has evolved to identify such genetic risk factors. Radiogenomics
      has two goals: (i) to develop an assay to predict which patients with cancer are
      most likely to develop radiation injuries resulting from radiotherapy, and (ii)
      to obtain information about the molecular pathways responsible for radiation
      induced normal-tissue toxicities. This review summarizes the history of the field
      and current research. SIGNIFICANCE: A single-nucleotide polymorphism-based
      predictive assay could be used, along with clinical and treatment factors, to
      estimate the risk that a patient with cancer will develop adverse effects from
      radiotherapy. Such an assay could be used to personalize therapy and improve
      quality of life for patients with cancer.

PMID- 24441287
TI  - Racial disparities in the prevalence of monoclonal gammopathies: a population
      based study of 12,482 persons from the National Health and Nutritional
      Examination Survey.
AB  - Multiple myeloma (MM) incidence is markedly higher in blacks compared with
      whites, which may be related to a higher prevalence of monoclonal gammopathy of
      undetermined significance (MGUS). Our objective was to define the prevalence and
      risk factors of MGUS in a large cohort representative of the US population.
      Stored serum samples from the National Health and Nutritional Examination Survey
      (NHANES) III or NHANES 1999-2004 were available for 12,482 individuals of age ?50
      years (2331 'blacks', 2475 Hispanics, 7051 'whites' and 625 'others') on which
      agarose-gel electrophoresis, serum protein immunofixation, serum-free light-chain
      assay and M-protein typing were performed. MGUS was identified in 365
      participants (2.4%). Adjusted prevalence of MGUS was significantly higher
      (P<0.001) in blacks (3.7%) compared with whites (2.3%) (P=0.001) or Hispanics
      (1.8%), as were characteristics that posed a greater risk of progression to MM.
      The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus
      South/West regions of the United States, respectively (P=0.052). MGUS is
      significantly more common in blacks, and more often has features associated with
      higher risk of progression to MM. A strong geographic disparity in the prevalence
      of MGUS between the North/Midwest versus the South/West regions of the United
      States was found, which has etiologic implications.

PMID- 24441289
TI  - Low-dose lenalidomide plus cytarabine induce complete remission that can be
      predicted by genetic profiling in elderly acute myeloid leukemia patients.

PMID- 24441288
TI  - Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive
      acute lymphoblastic leukemia: Children's Oncology Group study AALL0031.
AB  - We previously reported preliminary findings that post induction imatinib mesylate
      (340 mg/m(2)/day), in combination with intensive chemotherapy, resulted in
      outcomes similar to blood and marrow transplant (BMT) for pediatric patients with
      Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now
      report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1
      21 years) with and without allogeneic BMT (N=91). We explore the impacts of
      additional chromosomal abnormalities and minimal residual disease (MRD) by flow
      cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5
      patients, treated with chemotherapy plus imatinib (70%+/-12%, n=28), sibling
      donor BMT patients (65%+/-11%, n=21) and unrelated donor BMT patients (59+/-15%;
      P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse
      outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort
      5 or allogeneic BMT patients, although limited by small numbers. The re-induction
      rate following relapse was similar to other higher-risk ALL groups. Longer-term
      follow-up confirms our initial observation of substantially good outcomes for
      children and adolescents with Ph+ ALL treated with imatinib plus intensive
      chemotherapy with no advantage for allogeneic BMT.

PMID- 24441290
TI  - Targeting proliferation of chronic lymphocytic leukemia (CLL) cells through
      KCa3.1 blockade.

PMID- 24441291
TI  - Looking for CALR mutations in familial myeloproliferative neoplasms.

PMID- 24441292
TI  - An overview on CALR and CSF3R mutations and a proposal for revision of WHO
      diagnostic criteria for myeloproliferative neoplasms.
AB  - Disease-specific mutations facilitate diagnostic precision and drug target
      discovery. In myeloproliferative neoplasms (MPN), this is best exemplified by the
      chronic myeloid leukemia-associated BCR-ABL1. No other mutation in MPN has thus
      far shown a similar degree of diagnostic accuracy or therapeutic relevance.
      However, JAK2 and KIT mutations are detected in more than 90% of patients with
      polycythemia vera and systemic mastocytosis, respectively, and are therefore used
      as highly sensitive clonal markers in these diseases. JAK2 and MPL mutations also
      occur in essential thrombocythemia (ET) and primary myelofibrosis (PMF), but
      their diagnostic value is limited by suboptimal sensitivity and specificity. The
      molecular diagnostic gap in JAK2/MPL-unmutated ET/PMF is now partially addressed
      by the recent discovery of calreticulin (CALR) mutations in the majority of such
      cases. However, bone marrow morphology remains the central diagnostic platform
      and is essential for distinguishing ET from prefibrotic PMF and diagnosing
      patients those do not express JAK2, MPL or CALR (triple-negative). The year 2013
      was also marked by the description of CSF3R mutations in the majority of patients
      with chronic neutrophilic leukemia (CNL). Herein, we argue for the inclusion of
      CALR and CSF3R mutations in the World Health Organization classification system
      for ET/PMF and CNL, respectively.

PMID- 24441293
TI  - Predictive value of serum collagen biomakers on the outcome of acute myocardial
      infarction treated with percutaneous coronary intervention.
AB  - AIMS: This study was designed to investigate the predictive value of serum
      collagen biomarkers on the outcomes of acute ST-elevation myocardial infarction
      (STEMI) treated with percutaneous coronary intervention (PCI). METHODS: Two
      hundred and ten patients with STEMI were successfully treated with PCI within 6
      hrs ofthe onset of chest pain. The levels of serum procollagen type I
      carboxyterminal peptide (PICP) and procollagen type III peptide (PIIINP) were
      measured by enzymelinked immunosorbent assay (ELISA) before, 3 and 6 months after
      PCI. Left ventricular ejection fraction was assessed by echocardiography at 3 and
      6 months after PCI. The composite endpoints were death by any cause, recurrent
      myocardial infarction, heart failure or stroke. RESULTS: At the end of the 12
      month follow up, 29 patients (13.8%) experienced an end point. The level of serum
      PICP in patients with an end point was higher than in patients without an end
      point 7 days (19.45 +/- 2.17 vs 14.95 +/- 3.07 ng/mL, P<0.05) or 3 month after
      the PCI (29.87 +/- 3.02 vs 22.14 +/- 3.33 ng/mL, P<0.05). The serum PIIINP level
      in patients with an end point was also higher than those without 7 days after PCI
      (59.34 +/- 4.23 vs 48.78 +/- 4.23 ng/mL, P<0.05). Multivariate logistic
      regression analysis showed day 7 (OR=2.170, 95% CI 1.583-4.345, P=0.01) and 3
      month serum PICP (OR=2.340, 95% CI 1.431-4.650, P=0.01) were independent
      predictors of composite end points. CONCLUSIONS: Persistent elevation of serum
      collagen marker PICP three months after PCI predicts an adverse outcome for
      patients with acute ST-elevation myocardial infarction.

PMID- 24441294
TI  - Tobacco smoking, epilepsy, and seizures.
AB  - Tobacco smoking is considered the greatest risk factor for death caused by
      noncommunicable diseases. In contrast to extensive research on the association
      between tobacco smoking and diseases such as heart attack, stroke, and cancers,
      studies on the association between tobacco smoking and seizures or epilepsy are
      insufficient. The exact roles tobacco smoking and nicotine use play in seizures
      or epilepsy have not been well reviewed. We reviewed available literature and
      found that 1) there are vast differences between tobacco smoke and nicotine based
      on their components and their effects on seizures or epilepsy; 2) the seizure
      risk in acute active tobacco smokers, women who smoke during pregnancy,
      electronic cigarette smokers, and the role of smoking in sudden
      unexplained/unexpected death in epilepsy remain unclear; 3) seizure risks are
      higher in acute secondhand smokers, chronic active smokers, and babies whose
      mothers smoke; 4) tobacco smoke protects against seizures in animal models
      whereas nicotine exerts mixed effects in animals; and 5) tobacco smoking agents
      can be noneffective, proconvulsant, or anticonvulsant. Finally, the opportunities
      for future research on this topic is discussed. 

PMID- 24441296
TI  - From the editor.

PMID- 24441295
TI  - Sample preparation prior to molecular amplification: complexities and
      opportunities.
AB  - Molecular amplification using Reverse Transcription quantitative Polymerase Chain
      Reaction (RT-qPCR) is currently considered as the gold standard to detect enteric
      human pathogenic viruses such as norovirus and hepatitis A virus in food and
      water. However, the molecular-based detection requires an adequate sampling
      strategy and a sample preparation specific for viruses. Sampling for enteric
      human viruses in water and food should not necessarily follow bacterial sampling
      plans. The development of a reference detection method including sample
      preparation as proposed in ISO/TS 15216 represents a milestone to facilitate the
      evaluation of the performance and eventually validation of future virus detection
      methods. The potential viral infectivity linked to a positive PCR result is a
      remaining issue and pretreatments allowing the differentiation of infectious
      viruses would be useful for future risk assessments. 

PMID- 24441297
TI  - The elements of a positive workplace environment: implications for persons with
      disabilities.
AB  - A group of researchers from humanities, business, geography and rehabilitation
      science at McMaster University carried out a qualitative research study involving
      persons with disabilities in a south-western Ontario community. The study
      examined how persons with disabilities defined positive work environments both in
      paid work and volunteer activity. The study used a framework of organizational
      factors, social factors; social supports outside the workplace and individual
      characteristics. The study found that participants stressed the importance of
      positive attitudes, respect, understanding, communication and education as key
      components. 

PMID- 24441298
TI  - Time mastery in business and occupational therapy.
AB  - This article compares the results of an occupational therapy focused ethnographic
      study of time management with current concepts of time management in the business
      field. Researchers conducted in-depth interviews with six married working mothers
      to explore issues of time management. Qualitative analysis was used to identify
      four essential components, which are re-labeled Time Mastery: (1) Routines, (2)
      Instrumental and Social strategies, (3) Motivation, and (4) Cognitive Components.
      This occupational therapy model, is discussed within the context of Stephen
      Covey's 'four generations' of time management in the world of business: (1) Notes
      and checklists, (2) Calendars and appointment books, (3) Prioritization and goal
      setting and (4) Enhancing relationships and accomplishing results. Possible
      applications of the Time Mastery Model in work rehabilitation are suggested. 

PMID- 24441299
TI  - Group theories: relevance to group safety studies.
AB  - Promoting safety in the workplace has been attempted in a variety of ways.
      Increasingly, industries are using groups such as safety teams and quality
      circles to promote worker safety. Group influences on individual behavior and
      attitudes have long been studied in the social psychology literature, but the
      theories have not been commonly found outside the psychology arena. This paper
      describes the group theories of group polarization, risky shift, social loafing,
      groupthink and team think and attempts to apply these theories to existing
      studies that examine work group influences on safety. Interesting parallels were
      found but only one study examined group influences as their primary focus of
      research. Since groups are increasingly used for safety promotion, future
      research on safety that studies group influences with respect to current group
      theories is recommended. 

PMID- 24441300
TI  - The value of early placement in a supported employment program for individuals
      with traumatic brain injury.
AB  - Predicting return to work in persons with traumatic brain injury has been a
      challenge for doctors, rehabilitation therapists and vocational counselors.
      Although traditional vocational rehabilitation may be beneficial to many clients,
      there are others who are unable to return to work through customary means.
      Supported employment is a method of vocational rehabilitation in which a
      professional staff person (a job coach) provides structured job placement
      services and highly individualized training at the job site in addition to
      ongoing services throughout the entire length of employment. This approach has
      been used as a last resort to treatment, but has very high success rates (50-78%
      success rates for those deemed unemployable by other means). Work hardening was
      used in the 1980s as a last resort to therapy for the industrial injured worker.
      However, it was found that when clients entered the program sooner, they had a
      greater chance of return to work than if they entered the program after a
      prolonged period of time, thus saving money. If the individual with a traumatic
      brain injury is placed in supported employment programs sooner, he may have a
      greater chance of return to work than if supported employment is used only as a
      last resort. 

PMID- 24441301
TI  - Falls among Swedish nurses and nursing auxiliaries: types of injuries and their
      relation to age over time.
AB  - The study examines the age-related risk of fall injuries among female nurses and
      nursing auxiliaries in Sweden. Fall-injury ratios (FRs) were calculated, all
      injuries aggregated and for four injury types, employing five age categories and
      four reference years (1980-1995). Although there was a relationship between fall
      injury pattern and year of observation, in all years and for all injury patterns,
      nurses and nursing auxiliaries aged 45-54 and 55-65 years were the only age
      groups to register FRs substantially higher than 1.0. The findings suggest that
      patterns in injuries due to falls among these workers might be influenced by
      certain time-related conditions, but that general preventive priority should be
      given to workers aged 45 and over. 

PMID- 24441302
TI  - Body mechanics during daily tasks to reduce back pain in women who are pregnant.
AB  - Although pregnancy is a temporary condition, the prevalence of back pain has been
      estimated to be approximately 49-50% and pain may continue post partum. Often
      women have to limit or curtail daily living activities because of the pain. The
      purpose of this paper is to describe physical changes that occur during pregnancy
      and discuss positioning and body mechanics to prevent or reduce back pain during
      performance of self-care, homemaking and vocational activities. Suggested
      guidelines for continuation of various physical job demands and safety based on
      the American College of Obstreticians and Gynecologists are described. 

PMID- 24441303
TI  - The HomeSafe Pilot Program: a novel approach to injury prevention in residential
      construction.
AB  - Workers in the residential construction industry face unacceptably high risk of
      injury, disability and death. Attempts to implement comprehensive health and
      safety programs in this industry have met with little success. The HomeSafe Pilot
      Program is a novel residential construction safety program developed and
      sponsored by the Occupational Safety and Health Administration (OSHA) Region VIII
      and the Home Builders Association of Metropolitan Denver (HBA). Test subjects
      represent over 7475 persons employed in residential construction in the six
      county Denver Metro area of Colorado. The HomeSafe Pilot Program includes primary
      behavioral, engineering and administrative interventions to improve safe work
      practices in residential construction. It has some unique features of brevity,
      specificity and incentives not seen elsewhere in the construction industry. Its
      overall goal is to guide residential construction companies along a path of
      progressive development of comprehensive safety and health programs. The HomeSafe
      Pilot Program is introduced and compared to other safety and health program
      models developed by OSHA and the HBA. This study began in January 1997 and will
      continue through the millennium. 

PMID- 24441304
TI  - The relationship of compliance and grip strength return post-carpal tunnel
      release surgery.
AB  - This study examined the relationship of compliance and grip strength return 6
      weeks post-carpal tunnel release surgery on a sample of 11 factory workers
      residing in the midwest. The percent difference between pre-operative and post
      operative grip strengths was - 6.00%. An ANOVA ruled out age as a significant
      factor in grip strength return (F=1.20, P=0.351). A two sample t-test for gender
      differences in return of grip strength proved insignificant as well (t=1.01,
      P=0.351). The low negative correlation between participant self-report of
      compliance and percent difference of grip strength was - 0.426. Work was reported
      as the most significant barrier to compliance. Results of this study suggested
      that 6 weeks of occupational therapy may not be sufficient for recovery to pre
      operational grip strength status. Participants with the greatest amount of
      compliance in combination with returning to work soon after surgery demonstrated
      the weakest grip strength. This result implied that the exercise program in
      association with returning to work may have been too strenuous. Return to work
      and resulting work demands should be taken into consideration when prescribing
      home exercise programs. These conclusions are to be considered tentative and
      cannot be generalized because of the small sample size used to generate the data
      in this study. 

PMID- 24441305
TI  - Global health issues literacy: has the time come?
AB  - Understanding of patients' environments from a global perspective can enhance the
      positive effects of treatment. This understanding will entail expanding our
      definition of environment and community, and a consideration of all the
      environmental components and their inter-relationships. Submission of papers for
      this column is invited. 

PMID- 24441306
TI  - Rehabilitation ergonomists: standards for development.
AB  - Ergonomics, in the traditional definition, is the science of design of work sites
      and work methods which influence production performance. In recent years, worker
      complaints and reports of injuries have caused evaluation of the effect of work
      stressors on workers. Currently, the rehabilitation specialist plays a pivotal
      role in both prevention and management of physical work related complaints.
      Rehabilitation ergonomic practitioners combine a scientific background in
      function and pathology with the act of developing preventive or restorative
      remedies. A volunteer group of sixteen rehabilitation professionals who utilize
      ergonomic principles in the workplace developed a document, identifying job
      functions of the newly defined field. This paper presents philosophy and a model
      for educational development and potential credentialing areas for rehabilitation
      ergonomists. 

PMID- 24441307
TI  - The importance of a person-centered ecological approach to rehabilitation
      ergonomics: reply to Rice.

PMID- 24441308
TI  - Equifinality, multifinality, and immorality in a life of crime.

PMID- 24441310
TI  - Patient-centered medical homes or data-centered medical homes?

PMID- 24441311
TI  - Intermittent explosive disorder: a study in personalized psychopharmacotherapy.

PMID- 24441309
TI  - RNA families in Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) is a tumorigenic human gamma-herpesvirus, which produces
      several known structured RNAs with functional importance: two are implicated in
      latency maintenance and tumorigenic phenotypes, EBER1 and EBER2; a viral small
      nucleolar RNA (v-snoRNA1) that may generate a small regulatory RNA; and an
      internal ribosomal entry site in the EBNA1 mRNA. A recent bioinformatics and RNA
      Seq study of EBV identified two novel EBV non-coding (nc)RNAs with evolutionary
      conservation in lymphocryptoviruses and likely functional importance. Both RNAs
      are transcribed from a repetitive region of the EBV genome (the W repeats) during
      a highly oncogenic type of viral latency. One novel ncRNA can form a massive (586
      nt) hairpin, while the other RNA is generated from a short (81 nt) intron and is
      found in high abundance in EBV-infected cells. 

PMID- 24441312
TI  - Internal audit advice for nurse practitioner advocacy groups.

PMID- 24441317
TI  - LVAD: Left ventricular assist devices for end-stage heart failure.
AB  - Heart failure affects more than 5 million Americans with approximately 200,000
      patients in end-stage disease that has failed traditional treatment.
      Historically, the only option for treatment was a heart transplant until left
      ventricular assist devices offered another option.

PMID- 24441318
TI  - An oral health program for children.
AB  - Caries, the most infectious chronic disease of childhood in America, leads to
      health, learning, and quality-of-life issues. Using the Missouri Preventive
      Service Program model, a pilot oral health program for children from ages birth
      to 5 years in a rural health clinic was the first to implement the application of
      fluoride varnish.

PMID- 24441320
TI  - Biopsy of osteoporotic vertebral compression fractures.

PMID- 24441321
TI  - Genetics of idiopathic generalized epilepsy: an overview.
AB  - Idiopathic generalized epilepsy (IGE) is a common type of epilepsy. Strong
      support for a genetic role in IGE comes from twin and family studies. Several
      subtypes of IGE have been reported but families often have members affected with
      different subtypes. Major advances have been made in the understanding of genetic
      basis of monogenic inherited epilepsies. However, most IGEs are complex genetic
      diseases and some susceptible IGE genes are shared across subtypes that determine
      subtypes in specific combinations. The high throughput technologies like
      deoxyribonucleic acid microarrays and sequencing technologies have the potential
      to identify causative genes or loci in non-familial cases. 

PMID- 24441322
TI  - Not so "silent":the human prefrontal cortex.
AB  - Little was known about the human prefrontal cortex till recently. It was thus
      labeled as the "silent area," "uncommitted cortex." It not only constitutes the
      largest component of the human brain but is the latest evolutionary addition to
      the mammalian brain. It endows the human beings with qualities that differentiate
      humans from all other animals. During the last couple of decades the advent of
      modern electrophysiological and imaging (functional magnetic resonance imaging,
      proton emission tomography, SPECT) techniques have provided a wealth of insight
      into its role in memory, thought, emotions, moral judgment, social behavior,
      evaluating rewards, and assessing its fairness or otherwise and above all self
      awareness. This brief review summarize the recent significant observations on its
      functions and connectivity which would interest the cognitive scientists and
      clinicians alike. 

PMID- 24441323
TI  - Bifrontal basal interhemispheric approach for midline suprasellar tumors: our
      experience with forty-eight patients.
AB  - INTRODUCTION: Suprasellar lesions present a surgical challenge due to their
      complex relationship with surrounding neurovascular structures. Of the approaches
      for these lesions, bifrontal basal interhemispheric approach (BBIA) gives a
      midline perspective of suprasellar anatomy and has certain advantages over
      lateral approaches. MATERIALS AND METHODS: We retrospectively reviewed 48
      patients with suprasellar lesions operated over 7 years via BBIA. Patient
      records, operation notes, radiology, and outpatient files were scrutinized to
      collect data. RESULTS: During the study period 48 patients (mean age 33 years,
      M:F 1.5:1) were operated by this approach. The clinical features included: Visual
      field deficits in 33 (69%) patients, with 6 of them being blind, diabetes
      insipidus in 7, growth retardation in 5, and subarachnoid hemorrhage in three
      patients. Cranopharyngiomas (52%) and meningiomas (16.7%) were the most common
      pathologies. Dyselectrolytemia (18, 40%) and diabetes insipidus (15, 33%) were
      the most common complications. Postoperative seizures, meningitis, subdural
      effusion, and retraction site contusion were seen in 12 (27%), 5 (11%), 4 (9%),
      and 1 (2.2%) patient, respectively. Three patients died postoperatively and 19
      (40%) patients required hormone replacement therapy. Amongst the patients with
      preoperative visual deficits, 23 (70%) had improvement in visual functions, in
      six (20%), there was no change and four (8.3%) patients had visual deterioration.
      CONCLUSION: BBIA provides a true midline perspective and orientation, and permits
      complete and safe removal of midline suprasellar lesions in majority of cases.
      This approach is especially useful in retrochiasmatic tumors and in
      residual/recurrent tumors providing virgin plane of dissection.

PMID- 24441324
TI  - Simple transpedicular vertebral biopsy for diagnosis of malignancy in vertebral
      compression fracture.
AB  - BACKGROUND: The transpedicular route in percutaneous vertebroplasty (PVP) is a
      well-established approach for the treatment of vertebral compression fractures
      (VCFs). However, the value of simple transpedicular biopsy in VCFs is less
      addressed. The purpose of this study is to evaluate the value of transpedicular
      biopsy during PVP for uncovering the malignancy in VCFs in a 10-year
      retrospective study. MATERIALS AND METHODS: During the study period of the 1019
      patients who underwent PVP for VCFs, 450 patients comprising of 127 male and 323
      female underwent transpedicular biopsy during PVP for 705 fractured vertebras.
      The medical records were analyzed for age, gender, imaging studies, operation
      notes, pre-operative and post-operative diagnoses, date of vertebroplasty and
      biopsy, vertebral level and pathological reports. RESULTS: Pathology of the
      specimens of the 450 patients confirmed non-malignant VCFs in 389 (86.44%) and
      malignancy in 61 (13.56%). The malignant pathology included: 52 (11.56%) distant
      metastases to vertebra, in 3 (0.67%) of the spinal metastases was unsuspected and
      in 49 (10.89%) of them the malignancy was suspected pre-operatively. There were 9
      (2%) primary spinal malignancies, 2 (0.44%) unsuspected multiple myeloma and 7
      (1.56%) pre-operatively suspected primary malignancies. The frequency of
      unsuspected malignancy was 1.11% (5/450) in this study. There was no complication
      associated with transpedicular biopsy during PVP. CONCLUSIONS: VCFs harbored
      1.11% of unexpected malignancy. During the vertebroplasty, concomitant
      transpedicular vertebral biopsy is a safe and useful procedure for distinguishing
      non-malignant from malignant compression fractures, especially in diagnosing
      unsuspected malignancy.

PMID- 24441325
TI  - Endovascular treatment for unruptured small wide-necked ophthalmic segment
      aneurysms: technique feasibility, efficacy and mid-term follow-up.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of endovascular
      treatment (EVT) for unruptured small wide-necked ophthalmic segment aneurysms
      (OSAs) of the internal carotid artery (ICA). MATERIALS AND METHODS: Between
      January 2010 and May 2013, 17 patients with 19 unruptured small wide-necked OSAs
      received EVT. Occlusion rates were classified as total/near-total (95-100%),
      subtotal (80-95%) and partial (<80%) occlusions. This was determined by immediate
      and follow-up angiography. Follow-up outcome was assessed by using modified
      ranking scale (mRS). RESULTS: EVT was successfully performed in all the patients:
      Coiling only in 2 (10.5%) and stent-assisted coiling in 17 (89.5%) of the
      aneurysms. The immediate total/near-total occlusion was seen in 1 (5.3%), sub
      total occlusion in 8 (42.1%) and partial occlusion in 10 (52.6%). Follow-up
      angiography performed at 9.4 (+/-4.7) months revealed total/near-total occlusion
      in 13 (68.4%), subtotal occlusion in 5 (26.3%) and partial occlusion in 1 (5.3%).
      At the end of the follow-up period of 17.4 (+/-6.9) months, no aneurysm rupture
      was found and 16 (94.1%) of the patients had mRS scores of: Grade 0 in (5.9%) an
      mRS 1 in the remaining. CONCLUSIONS: EVT may be feasible and effective treatment
      option for unruptured small wide-necked ophthalmic aneurysms of the ICA.

PMID- 24441326
TI  - Histological changes in thalamus in short term survivors following traumatic
      brain injury: an autopsy study.
AB  - BACKGROUND: Severe traumatic brain injury (TBI) is a major cause of morbidity and
      mortality. Reduction of thalamic volumes were seen in upto 80% of patients who
      survived for more than 3 months after TBI. However, the same may not be true in
      patients who died earlier following TBI. AIMS: To to study the thalamus for
      evidence of any injury in short term survivors of TBI (<5 days) using
      immunohistochemistry to look for evidence of acute thalamic injury. MATERIALS AND
      METHODS: A cross sectional prospective study was done in which autopsy specimens
      of short term survivors of TBI (<5 days) were studied for histopathological
      changes. RESULTS: A total of 16 patients with a mean age of 37.8 years were
      included in the study. CT scan revealed acute subdural haematoma in 10,
      contusions in 4 patients, extradural haematoma and depressed fracture in 1 each,
      and diffuse axonal injury in 1 patient. Seven patients required surgery in the
      form of a decompressive hemicraniectomy. The histopathological analysis of the
      bilateral thalami showed evidence of congestion of the cerebral capillaries in 8
      patients. Axonal retraction balls were seen in 8 patients, myelin breakdown
      products were seen in 14 patients and axonal swelling was seen in 14 patients.
      CONCLUSIONS: Thalamic injury is universal in the setting of severe TBI in
      patients who have decreased survival and may be a significant factor for the poor
      outcome in these patients.

PMID- 24441327
TI  - Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal
      fluid of patients with moderate and severe traumatic brain injury.
AB  - OBJECTIVE: In this study, we investigated matrix metalloproteinases (MMPs) and
      tissue inhibitor of metalloproteinase (TIMPs) in cerebrospinal fluid (CSF) and
      plasma of traumatic brain injury (TBI) patients. PATIENTS AND METHODS: A total of
      30 patients with moderate and severe TBI and 15 age-matched controls were
      enrolled in this study. Plasma and CSF samples were collected within 24 h (as the
      initial value), at 72 and 120 h post injury. CSF and plasma MMP-9, MMP-2, TIMP-1
      and TIMP-2 were estimated using ELISA. Different levels of these indexes were
      compared in the two groups and further investigated the correlation between each
      other. RESULTS: There was a significant elevation in the levels of the initial
      MMP-9 in the CSF (P < 0.05), which lasted for 72 h post injury. TIMP-1 kept
      increasing within 120 h post injury and it was different compared with TIMP-1 at
      24 and 72 h post injury. Plasma levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 in TBI
      patients were also significantly different from those in controls. Furthermore
      the CSF MMP-9 in patients with severe TBI was higher than that in patients with
      moderate TBI. In addition, there was a positive relationship between the initial
      MMP-9 and TIMP-1 at 120 h post injury (r = 0.614, P < 0.01). CONCLUSION: MMPs and
      TIMPs are increased in both CSF and plasma of TBI patients. TIMP-1 has a positive
      correlation with MMP-9 and the initial MMP-9 is associated with the neurological
      outcomes.

PMID- 24441328
TI  - Use of viber app: a fast, easy and cost effective method of communication in
      neurosurgery.
AB  - OBJECTIVE: Neurosurgeons often have to rely on judgments of junior staffs to
      decide on patients whom they cannot attend immediately. Viber is a free to use
      application for image transfer on Internet. We evaluated the use of viber in
      neurosurgical scenario, to show it is cheap, fast, accessible, reliable and
      feasible. MATERIALS AND METHODS: We conducted a prospective study from March 2013
      to July 2013. Residents were taught to take sharp pictures and upload them
      immediately using viber on Internet. Primary endpoints were discordance between
      opinion of residents and consultants on viber images and subsequent actual image
      evaluation and time delay in decision-making. Discordance was considered
      significant if it changed management decision. RESULTS: During the study period,
      120 (mean age: 42 years, 58% males) patients were enrolled. Wi-Fi is freely
      available in the institute and thus no costs were involved. Decision could be
      made on images received on viber at an average of 20 min. There was discordance
      in 56.7% cases between residents' reports and images on viber, which was
      significant in 88.2% cases. However in 5% cases decision changed after actual
      images were reviewed. Of all imaging modalities, computed tomography angiographic
      images were associated with statistically significant discordance (P <0.05).
      CONCLUSION: This study suggests that the use of viber app in neurosurgery can be
      an easy fast reliable and almost free mode of communicating images enabling a
      quick decision. However this cost-effective method should be used with caution
      particularly with imaging modalities, which require processing and review on
      console.

PMID- 24441329
TI  - Major histocompatibility complex and inflammatory cell subtype expression in
      inflammatory myopathies and muscular dystrophies.
AB  - BACKGROUND: In inflammatory myopathies muscle biopsy is a crucial diagnostic
      test. Misinterpretation between inflammatory myopathies and muscular dystrophies
      with inflammation is known. MATERIALS AND METHODS: Thirty-one patients clinically
      and pathologically diagnosed to have polymyositis and dermatomyositis and 16
      patients of muscular dystrophy with inflammation were studied for MHC-I, MHC-II,
      CD4 and CD8 expression in skeletal muscle tissue. RESULTS: MHC-I upregulation was
      noted in all samples of PM and DM. Interstitial and perivascular inflammation in
      PM were predominantly CD8+ cells, in dermatomyositis, interstitial and perimysial
      perivascular inflammatory cells were CD4+ T cells and CD8+ T cells were seen
      around endomysial vessels. Interestingly MHC-I upregulation was seen in all 16
      cases of muscular dystrophy with presence of inflammation. CONCLUSION: The
      pattern of MHC-I and II expression appeared to be similar in both inflammatory
      myopathies as well as in muscular dystrophies with inflammation and hence
      differentiating them on MHC - I expression was difficult.

PMID- 24441330
TI  - New mutation of the desmin gene identified in an extended Indian pedigree
      presenting with distal myopathy and cardiac disease.
AB  - In this report, we describe a new mutation located in the coiled 1B domain of
      desmin and associated with a predominant cardiac involvement and a high degree of
      cardiac sudden death in a large Indian pedigree with 12 affected members. The
      index cases was 38-year-old man who presented with progressive difficulty in
      gripping footwear of 5 years duration with the onset in the left lower limb
      followed by right lower limb in 6 months. 3 years from onset, he developed lower
      limb proximal and truncal muscle weakness. There was mild atrophy of the shoulder
      girdle muscles with grade 3 weakness, moderate wasting of thigh and anterior leg
      muscles with proximal muscle weakness and foot drop. At 40 years, he had a
      pacemaker implanted. The 9 exons and intronic boundaries of the desmin gene were
      sequenced and a heterozygous nucleotide change c. 734A > G in exon 3 was
      identified. 

PMID- 24441331
TI  - Cost of stroke from a tertiary center in northwest India.
AB  - AIM: We aimed to study the cost of stroke, its predictors, and the impact on
      social determinants of the family. SETTINGS AND DESIGN: This prospective study
      was done in the Stroke unit and Neurology clinic between April 2009 and October
      2011. MATERIALS AND METHODS: All first ever stroke patients during the study
      period were enrolled. Direct and indirect costs at admission, at 1 and 6 months
      follow-up were obtained. The follow-up included information about the patient's
      poststroke outcome using modified Rankin Scale (mRS), work status, modifications
      made at home, loan requirement, etc., RESULTS: Two hundred patients were enrolled
      in this study and final analysis was performed on 189 patients. The mean age was
      58 +/- 13 years and 128 (67.7%) were men. Majority (54%) were living in a joint
      family. The mean overall cost of stroke per patient was rupees (INR) 80612 at 6
      months. Higher income (P = 0.008), poor outcome (mRS >2) (P = 0.001), and length
      of hospital stay (P = 0.001) were the cost driving factors of total cost of
      stroke at 6 months. There was a decline in the requirement of help (P < 0.0001)
      and need for loan (P = 0.003) at 6 months follow-up. CONCLUSIONS: Direct medical
      cost or acute care of stroke accounted for a major component of cost of stroke.
      Poor outcome, length of hospital stay, and higher income were the cost driving
      factors. The socioeconomic impact on the family decreased at follow up probably
      due to joint family system.

PMID- 24441332
TI  - Categorized hospital charges of acute ischemic stroke according to trial of org
      10172 in acute stroke treatment classification.
AB  - BACKGROUND: Previous studies have shown that the cost of hospitalization due to
      stroke is significantly associated with the length of stay, stroke severity and
      other clinical characteristics, as well as various socio-demographic factors.
      However, these studies have been rather inconsistent with regard to the influence
      of stroke subtypes on costs. AIMS: This study was examined and compared hospital
      charges of in-patients with acute ischemic stroke according to the Trial of Org
      10172 in Acute Stroke Treatment classification. MATERIALS AND METHODS: The costs
      of case of 749 patients with first ever ischemic stroke who were admitted to an
      academic medical center between January 2006 and December 2008 were analyzed. The
      hospital charges were compared among the stroke subtypes using Analysis of
      Variance. Multiple regression analyses were further performed to test the
      significance of the impact of the stroke subtype after controlling for other
      variables. RESULTS: The stroke subtype turned out to be a statistically
      significant factor influencing both the total charge and several categorized
      charges even after controlling for other contributing factors such as hospital
      length of stay and stroke severity. CONCLUSIONS: This study concludes that the
      stroke subtype should be included when considering in-patient medical expenses of
      acute ischemic stroke.

PMID- 24441333
TI  - Solitary cerebral parenchymal cysticercosis: a prospective comparative study with
      computed tomography and magnetic resonance imaging.
AB  - AIM: To present a prospective series of 86 patients with solitary cerebral
      cysticerci who underwent both contrast computed tomography (CT) and contrast
      magnetic resonance imaging (MRI), and to correlate and compare the imaging
      findings using these two modalities. MATERIALS AND METHODS: Lesion
      characteristics, staging of the cyst and perilesional hypodensity on CT and
      hyperintensity on MRI were analyzed, and the lesion was described with regard to
      the appearance of the scolex, cyst fluid, cyst wall and the perilesional area.
      RESULTS: Patients were largely children and adolescents (mean age 17.4 years,
      range 6-52) with 52.3% males. MRI was performed, on average, 10.7 days after CT.
      MRI was more sensitive than plain CT scan in detecting cysticercal lesions (P =
      0.003), but there was no statistically significant difference between contrast CT
      and MRI. None of the patients were detected with an alternative disease on serial
      MRI. No cyst showed significant mass effect. Non-contrast CT was less sensitive
      than either contrast CT or MRI in detecting the scolex (P = 0.011), but no
      difference was seen between the latter two modalities. Qualitative imaging
      characteristics of the cysticercus on MRI and CT scan are described. All cysts
      were round in shape, with an average diameter of <10 mm, and maximum diameter of
      19 mm. CONCLUSION: In the present prospective series, contrast CT was nearly as
      sensitive as MRI in detecting solitary cerebral cysticerci. Thus, in highly
      resource-limited settings contrast CT may be sufficient for the diagnosis and
      management of neurocysticercosis.

PMID- 24441334
TI  - Recurrent meningeal inflammatory myofibroblastic tumor: a case report and
      literature review.
AB  - An inflammatory myofibroblastic tumor (IMT) is a rare lesion with an uncertain
      prognosis and a disorder difficult to classify. IMTs are a heterogeneous group of
      lesions, sometimes indistinguishable from meningiomas and other expanding or
      inflammatory lesions of the central nervous system. This report presents a
      patient with IMT, who presented with recurrent retroocular pain radiating to the
      occipital region and no neurologic deficits. He had early recurrence in spite of
      total resection of the lesion. The clinical profile of 18 patients with either
      progression or recurrence has been reviewed. 

PMID- 24441335
TI  - Indocyanine green video angiography-assisted surgical management of coil
      migration resulting from the endovascular treatment of anterior communicating
      artery aneurysm: technical case report and instrumentation assessment.
AB  - We describe surgical management of herniated coil using indocyanine green video
      angiography (ICGA) following failure of endovascular retrieval methods in a
      patient who had endovascular treatment for anterior communicating artery
      aneurysm. The interdisciplinary cooperation between the endovascular and
      neurosurgical teams proved to be crucial for obtainment of a desirable outcome in
      this case. ICGA technology applied in such difficult cases may improve the
      surgical outcome. 

PMID- 24441336
TI  - Chin fasciculations in Madras motor neuron disease: a new clinical feature.
AB  - The characteristic features of Madras motor neuron disease (MMND) are onset in
      the young in the first two decades, sporadic occurrence, facial and bulbar
      paralysis, sensorineural hearing impairment, asymmetrical weakness of limbs and
      pyramidal signs with a slow progression. The majority of the cases reported are
      from South India. MMND variant has the additional features of optic atrophy and
      cerebellar signs. We are reporting a 48 year old female of MMND who had
      persistent fasciculations of chin, with electromyographic features of
      fasciculations and fibrillations in mentalis muscle. Chin fasciculations, a rare
      clinical feature, is now described for the first time in Madras motor neuron
      disease adding a new feature to the clinical constellation of symptoms. 

PMID- 24441337
TI  - Neurocysticercosis presenting as parkinsonism.

PMID- 24441338
TI  - Prolonged thiamphenicol treatment associated sensory axonal polyneuropathy.

PMID- 24441339
TI  - Vacuum sinus headache: an uncommon presentation of a giant frontal osteoma.

PMID- 24441340
TI  - Intraneural capillary hemangioma: a rare cause of proximal median neuropathy.

PMID- 24441341
TI  - Acute thrombotic occlusion of internal carotid artery: a rare neurological
      presentation of acute promyelocytic leukaemia.

PMID- 24441342
TI  - Post-operative intradural tension pneumorrhachis.

PMID- 24441343
TI  - Extraocular muscle cysticercosis mimicking as pseudotumor orbit: a clinical
      dilemma.

PMID- 24441344
TI  - Revisiting Eiffel- at night, in brain....

PMID- 24441345
TI  - Sciatica caused by pyomyositis of the piriformis muscle.

PMID- 24441346
TI  - A rare cause of dural venous sinus thrombosis.

PMID- 24441347
TI  - Brucella melitensis shunt infection.

PMID- 24441348
TI  - Thyrotoxic hypercoagulable state with cerebral venous thrombosis and venous
      infarction masquerading as epilepsia partialis continua.

PMID- 24441349
TI  - A new Indian family affected by gelsolin amyloidosis.

PMID- 24441350
TI  - Subependymoma causing conus-cauda syndrome: cured by total excision.

PMID- 24441351
TI  - Primary pilomyxoid astrocytoma of the thoracolumbar spinal cord in an adult.

PMID- 24441352
TI  - Foot drop caused by cerebral cavernous angioma.

PMID- 24441353
TI  - Single, small, spontaneous, accessory, closed type, frontal sinus pericranii in a
      child: favorable outcome with surgical excision.

PMID- 24441354
TI  - Hearing improvement following gamma knife radiosurgery for an intra-canalicular
      vestibular schwannoma.

PMID- 24441355
TI  - Primary leiomyoma of the parietal bone.

PMID- 24441356
TI  - Ependymoma: Unusual differential for a totally extramedullary intraspinal tumor.

PMID- 24441357
TI  - Complete and curative excision of hypothalamic hamartomas via the orbito
      zygomatic approach.

PMID- 24441358
TI  - Anterior cervical meningomyelocele in a neonate.

PMID- 24441359
TI  - Frontal sinus osteoma with pneumocephalus and progressive hemiparesis.

PMID- 24441360
TI  - Drop finger as an adjacent segment disease after cervical expansive laminoplasty.

PMID- 24441361
TI  - Magnetic resonance angiography diagnosis of infundibula occurring at an unusual
      location: Source image should not be overlooked.

PMID- 24441362
TI  - Ruptured pseudoaneurysm of the superficial temporal artery after craniotomy.

PMID- 24441363
TI  - Mobile floating carotid plaque in a young woman.

PMID- 24441364
TI  - Comment on "Susceptibility-weighted imaging: the value in cerebral astrocytomas".

PMID- 24441365
TI  - Endoscopic repair of CSF rhinorrhea: necessity of fibrin glue.

PMID- 24441366
TI  - Dehydration improves cryopreservation of mat rush (Juncus decipiens Nakai) basal
      stem buds on cryo-plates.
AB  - Two cryopreservation procedures using aluminium cryo-plates, termed V-Cryo-plate
      and D-Cryo-plate, were successfully developed for in vitro mat rush (Juncus
      decipiens Nakai) basal stem buds. Multiple stems induced in liquid MS medium
      containing 8.9 MUM BA by roller culture were cut into small clumps, plated on
      solid MS medium and cultured for 1 week at 25 degree C. Clumps that had produced
      many buds were cold-hardened at 5 degree C for 1-2 months. The buds with basal
      stems were dissected from small clumps and precultured overnight at 25 degree C
      on solid MS medium containing 0.3 M sucrose. Precultured buds were placed on
      aluminium cryo-plates and embedded in calcium alginate gel. Osmoprotection was
      performed by immersing the cryo-plates for 30 min at 25 degree C in loading
      solution (2 M glycerol + 1.0 M sucrose). In the D-Cryo-plate procedure, the buds
      were dehydrated to 27-25% moisture content (fresh weight) by placing the cryo
      plates in the air current of a laminar flow cabinet for 2 to 3 h. In the V-Cryo
      plate procedure, buds were dehydrated by immersing the cryo-plates in PVS2
      vitrification solution for 40 min at 25 degree C. In both procedures, cooling was
      performed by placing the cryo-plates in uncapped cryotubes, which were immersed
      in liquid nitrogen. For rewarming, cryo-plates were immersed in medium with 1.0 M
      sucrose for 20 min at room temperature. Regrowth of cryopreserved buds of line
      'Kitakei 2' using D-Cryo-plate and V-Cryo-plate procedures, was 90% and 80%,
      respectively. The two procedures were applied to 20 additional mat rush lines.
      Using the V-Cryo-plate procedure resulted in regrowth ranging between 13.3 and
      86.7%, with an average of 52.5%. The D-Cryo-plate led to regrowth ranging between
      73.3 and 96.7%, with an average of 86.3%. The D-Cryo-plate procedure will
      facilitate cryostorage of mat rush germplasm. 

PMID- 24441367
TI  - Cryopreservation of Phaeocystis antarctica.
AB  - A large number of clonal isolates of the prymnesiophyte Phaeocystis antarctica
      have been established at the Alfred Wegener Institute in Bremerhaven, Germany, to
      address questions on the genetic diversity and ecological response patterns to
      climate change. However, at present the wider scientific community cannot access
      these strains and their long-term conservation, (currently by serial transfer),
      cannot be assured. Cryopreservation could provide the solution to these issues,
      as it would guarantee the long-term security of this genetically and ecological
      invaluable collection. This study outlines the successful application of
      conventional approaches and the use of novel, combined non-penetrating and
      penetrating cryoprotective strategies that have been successfully applied to the
      different life-stages of this alga. 

PMID- 24441368
TI  - Cryopreservation of Arachis pintoi (leguminosae) somatic embryos.
AB  - In this study, we successfully cryopreserved cotyledonary somatic embryos of
      diploid and triploid Arachis pintoi cytotypes using the encapsulation-dehydration
      technique. The highest survival rates were obtained when somatic embryos were
      encapsulated in calcium alginate beads and precultured in agitated (80 rpm)
      liquid establishment medium (EM) with daily increasing sucrose concentration
      (0.50, 0.75, and 1.0 M). The encapsulated somatic embryos were then dehydrated
      with silica gel for 5 h to 20% moisture content (fresh weight basis) and cooled
      either rapidly (direct immersion in liquid nitrogen, LN) or slowly (1 degree C
      per min from 25 degree C to -30 degree C followed by immersion in LN). Beads were
      kept in LN for a minimum of 1 h and then were rapidly rewarmed in a 30 degree C
      water-bath for 2 min. Finally, encapsulated somatic embryos were post-cultured in
      agitated (80 rpm) liquid EM with daily decreasing sucrose concentration (0.75 and
      0.5 M) and transferred to solidified EM. Using this protocol, we obtained 26% and
      30% plant regeneration from cryopreserved somatic embryos of diploid and triploid
      cytotypes. No morphological abnormalities were observed in any of the plants
      regenerated from cryopreserved embryos and their genetic stability was confirmed
      with 10 isozyme systems and nine RAPD profiles. 

PMID- 24441369
TI  - Programmed cell death and necrosis during cryopreparative drying of in vitro
      Eucalyptus grandis axillary buds.
AB  - In preparation for cryopreservation, Eucalyptus grandis in vitro axillary buds
      were dried over silica gel. Pretreatment of the buds with 5 mg per L ABA resulted
      in partial resistance to water loss (0.76 to 0.45 g per g fresh mass basis) as
      compared with untreated buds (0.76 to 0.33 g per g) and was associated with the
      retention of viability (70 vs. 55%). The loss of viability of the dried buds was
      protracted over several days. Ultrastructural examination and vital staining
      demonstrated cellular and tissue responses to drying. The meristem appeared to
      withstand drying and 72 h of rehydration whilst the leaf primordia were destroyed
      immediately after drying. High reactive oxygen species (ROS) activity was
      associated with bud excision and drying. Caspase-3-like protease activity was
      detected after rehydration, thereby providing evidence that the dried buds, that
      had ultimately died, had undergone programmed cell death. ROS production is
      considered to be the trigger for programmed cell death. 

PMID- 24441371
TI  - Cryopreservation of eucalyptus genetic resources.
AB  - The long-term preservation of forest genetic resources is a vital part of
      preserving our forest crops for future generations. Unfortunately, there are few
      genebanks dedicated to forest trees and very few methods for long-term
      preservation of forest genetic resources collections aside from field plantings
      of a limited number of seed-derived or elite clonal individuals. The use of
      cryopreservation for the long-term storage of elite germplasm is increasingly
      being used for the long-term preservation of clonal agronomic crops but for
      forest trees, such as Eucalyptus, the methodology for cryopreservation of diverse
      genetic resources collections has not been established. We report the successful
      cryopreservation of a germplasm collection of in vitro shoot cultures of thirteen
      Eucalyptus spp. lines consisting of two E. grandis x E. camaldulensis lines,
      seven E. urophylla x E. grandis lines, one E. grandis line, two E. grandis x E.
      urophylla lines, and one E. camaldulensis line. In a comparison of two
      cryopreservation methods, sucrose sensitivity limited the application of
      encapsulation-dehydration. However, with droplet-vitrification, all thirteen
      lines had good survival after cryopreservation in liquid nitrogen. A 30 min
      exposure to Plant Vitrification Solution 2 (PVS2) yielded post-liquid nitrogen
      survival between 38% and 85% depending on the line. One hundred shoot tips from
      all thirteen lines are currently in long-term storage as a germplasm collection. 

PMID- 24441370
TI  - A new modified cut standard straw vitrification technique reduces the apoptosis
      of mouse blastocysts and generates more live mouse offspring.
AB  - Effects of freezing on apoptosis and autophagy in embryos are poorly understood.
      This study introduces a simple and successful method (modified cut standard
      straw, M-CSS) for cryopreservation of mouse zygotes. Apoptosis and autophagy were
      investigated in cultured mouse blastocysts derived from vitrified zygotes using
      two vitrification containers (M-CSS vs 0.25-ml straw). The percentages of zygotes
      that survived and developed into blastocysts and the number of cells per
      blastocyst were higher in the M-CSS group than in the 0.25 ml straw group;
      whereas the rate of apoptosis in blastocysts was significantly lower in the M-CSS
      group than in the 0.25-ml straw group. The expression of the apoptosis-related
      gene Caspase 3 in blastocysts was higher in the 0.25-ml straw group than in the M
      CSS group; however, there were no significant differences in autophagy between
      these two groups. Vitrified-thawed mouse zygotes were transferred into
      recipients. The percentage of recipients that became pregnant and the percentage
      of transferred zygotes that developed into live offspring were significantly
      lower in the 0.25-ml straw group than in the M-CSS (10.2% vs. 17.5%). In
      conclusion, the novel M-CSS procedure improves oocyte and embryo vitrification.
      The standard 0.25-ml straw vitrification procedure induces mitochondrial
      apoptosis in zygotes in an autophagy-independent manner. 

PMID- 24441372
TI  - X-ray diffraction study confirms intra-adipocitary lipid crystallization after
      lipocryolysis stimulus.
AB  - Lipocryolysis always claimed localized-fat-reduction to be a consequence of local
      apoptotic adipocyte destruction triggered by intracellular triglyceride
      crystallization. The idea is now under debate, for it has been suggested that the
      physical changes occurring in adipocytes after lipocryolysis could be better
      explained by a lipid gel-like transition process rather than by lipid
      crystallization. Since a) lipocryolysis claims apoptosis to be the key to
      adipocyte destruction and clinical-result achievement and b) it considers
      crystallization to be a necessary step for the apoptotic stimulus unleashing, any
      effort to untangle, prove or discard this process is very important. 

PMID- 24441373
TI  - Cryosurvival of in vitro produced embryos as affected by health status effect of
      oocyte donor cow.
AB  - In vitro embryo production and embryo vitrification of genetically superior cows
      that culled inevitably due to health problems can accelerate genetic progress.
      This study was carried out to investigate whether maternal age and health status
      effects of high genetic merit cows affect cryosurvival and developmental
      competence of IVP embryos. In this sense, the effects of ageing and four common
      culling causes of dairy cows [repeat breeding (RPB), udder problems (UPM),
      chronic endometritis (CRE), and lameness (LAM)] on in vitro embryo development,
      and in vivo developmental competence after embryo vitrification were evaluated.
      The mean number of oocytes obtained per cow did not vary significantly between
      donors indifferent groups. Cleavage rates in RPB (86.0+/-4.2%), SEN (81.3+/-2.5%)
      and CRE (77.6+/-6.3%) cows which were comparable to control (95.9+/-1.5%) but
      were significantly higher than the related rate of UPM donors (50.6+/-2.6%).
      Importantly, there was no significant difference between the blastocyst rates of
      different groups. Mean overall survival rate was not different between the groups
      and was not affected by the blastocyst production rate. There was no significant
      difference between pregnancy rates of different groups. The results of the
      present study indicated that in cattle, neither ageing, nor these four diseases
      affect ovarian potential in terms of the yield and quality of in vitro embryo
      development. 

PMID- 24441375
TI  - From the editor.

PMID- 24441374
TI  - Effect of Cytochalasin B pretreatment on developmental potential of ovine oocytes
      vitrified at the germinal vesicle stage.
AB  - Oocyte cryopreservation remains a challenge in most mammalian species because of
      their sensitivities to chilling injuries. Relaxation of the cytoskeleton during
      vitrification may improve post-thaw viability and pre-implantation embryo
      development. The aim of this study was to investigate the effect of cytochalasin
      B (CB) pre-treatment before vitrification on viability, frequencies of in vitro
      fertilisation (IVF) and subsequent development of ovine cumulus-oocyte complexes
      (COCs) vitrified at the germinal vesicle (GV) stage using cryoloop. COCs obtained
      at slaughter were randomly divided into two groups and incubated with or without
      7.5ug/mL CB for 60 min. Oocytes from each group were then vitrified using a
      cryoloop or used as toxicity and controls. Oocytes were then matured, fertilised,
      and cultured in vitro for 7 days. Viability following vitrifiaction and warming,
      fertilisation events following IVF and subsequent pre-implantation embryo
      development were evaluated. No significant differences were observed in survival
      rates between CB treated and non-treated oocytes in both vitrified and toxicity
      groups. Frequencies of fertilisation were increased in CB-vitrified group
      (oocytes pre-treated with CB before vitrification) than those vitrified without
      CB pre-treatment (57.0% vs 40.7%). Cleavage was significantly lower (P < 0.05) in
      vitrified and CB-vitrified oocytes at both 24 hpi (12.5% vs 9.1%) and 48 hpi
      (25.0% vs 16.2%) than in other groups. Based on the numbers of cleaved oocytes,
      (48 hpi), 16.1% and 18.8% of the cleaved embryos developed to blastocysts in both
      vitrified and CB-vitrified groups. These values did not differ significantly from
      those obtained in CB-control group (37.8%). No significant differences were
      observed in mean cell numbers per blastocyst between all groups. In conclusion,
      pre-treatment of ovine GV oocytes with cytochalasin B as cytoskeleton stabilizer
      before vitrification increased frequencies of in vitro fertilisation and
      subsequently resulted in production of good quality late stage pre-implantation
      embryos following IVF. 

PMID- 24441376
TI  - Impact of carpal tunnel education on changing dental hygienists knowledge, risk
      behaviors, symptoms and functional performance.
AB  - In recent years, occupational therapists have become increasingly involved in the
      design and implementation of carpal tunnel syndrome (CTS) prevention programs.
      The purpose of this paper is to examine the effect of an occupational therapists'
      designed and implemented CTS educational program targeted to address risk
      behaviors in the dental hygiene profession. A total of 79 practicing dental
      hygienists completed a pre, post, and 2-week follow-up questionnaire to measure
      the extent of change in knowledge of CTS symptoms, "at risk behaviors", and
      prevention strategies before and after CTS education. The findings of this study
      suggest that the CTS educational program, presented by an occupational therapist
      and a registered dental hygienist, significantly impacted dental hygienist's CTS
      knowledge and lead to positive changes in their "at risk behaviors" and use of
      prevention strategies. 

PMID- 24441377
TI  - What prevents people with disabilities from obtaining employment? An examination
      of Canadian data from a national and regional perspective.
AB  - People with disabilities who are able to be employed have historically had to
      struggle with a number of barriers related to workplace activities. In recent
      years, more data has become available regarding employment in general and for
      people with disabilities in particular. As major stakeholder groups (people with
      disabilities, service provider agencies, funders and employers) move to a more
      integrated and equitable approach, it is essential that data related to
      employment for people with disabilities not be esoteric but utilitarian. This
      article will review a Canadian regional study that is being used to help shape
      vocational services for people with disabilities and will compare the findings to
      the Canadian national scene. 

PMID- 24441378
TI  - Empirical finding on the external validity of patient assault vignettes.
AB  - We had the nurses who were victims of actual assaults (n=29) use the 'blame'
      scales we have used in our last two written vignette studies to assign blame for
      their assault, and then we had three judges use the same scales to assign blame
      for the assault based on a written description of the assault by the victim. No
      significant difference in mean blame levels were found between victims and the
      average ratings for the three judges, or between victims, judges and the response
      levels obtained in our prior two studies. The mean 'blame' scores observed in
      written assault vignettes, therefore, are relatively and approximately the same
      as those that are, or will be observed in actual assaults. 

PMID- 24441379
TI  - Performance components predictive of errors resulting in motor vehicle crashes in
      older drivers.
AB  - Numerous skills and abilities are necessary in the operation of an automobile.
      Many of these skills and abilities deteriorate with age. These deteriorations,
      coupled with the increased incidence of motor vehicle crashes in terms of number
      of miles driven for older drivers, makes it imperative to explore the
      relationship between these factors. A review of the literature was utilized to
      present the performance components of older drivers that may contribute to motor
      vehicle crashes. Vision and attention appear to play a major role, particularly
      in the types of accidents that occur most frequently to this population -
      intersection accidents. This article consolidates the existing literature from
      several disciplines. This is especially needed for occupational therapy
      practitioners, with their growing involvement in the assessment and
      rehabilitation of driving skills. 

PMID- 24441380
TI  - Identification of the variables relevant to the recovery from post-surgical
      carpal tunnel syndrome.
AB  - The purpose of this paper is to determine what variables have been found to
      predict successful outcome for patients who have undergone carpal tunnel release
      surgery. In this case, 'successful' is defined as long-term relief of symptoms,
      pain free functional performance, or return to work. The variables have been
      divided into three major groups. The first group is the variables that relate to
      the individual. The second group is those variables that relate to the person's
      employment. The last group of variables to be discussed are those that relate to
      society. From this literature review, it appears that there are a significant
      number of variables that are 'relevant' to the recovery from carpal tunnel
      release surgery. However, the research conducted thus far has produced few
      results that identify any consistently reliable 'predictors' of surgical outcome.
      Future studies will require that a greater degree of reliability and validity be
      established for these variables. In addition, a clear and consistent definition
      of success with specific criteria for recovery will be necessary. 

PMID- 24441381
TI  - Knowledge about AIDS and attitudes towards persons with AIDS: Implications for
      occupational therapy.
AB  - Persons with acquired immunodeficiency syndrome (AIDS) are frequent users of
      healthcare services, and their care presents a critical challenge to the
      healthcare profession. With an estimated one million persons in the United States
      believed to be infected, occupational therapy practitioners will see increasing
      numbers of referrals to provide services to persons with AIDS. Like other
      healthcare professionals, occupational therapy practitioners have expressed
      inaccurate knowledge about AIDS and negative attitudes towards persons with AIDS,
      both affecting the therapeutic relationship, and possibly leading to suboptimal
      clinical care. This paper summarizes research that measures healthcare
      professionals' knowledge and attitudes about AIDS. It also explores the
      effectiveness of educational programs aimed at increasing knowledge about AIDS
      and modifying attitudes towards persons with AIDS. Further research is proposed
      in the occupational therapy field to assist in the development of educational
      programs addressing these important AIDS issues. 

PMID- 24441382
TI  - Demonstrating therapeutic interventions for the remediation of symptoms
      associated with trauma-induced carpal tunnel syndrome: An illustrated case
      report.
AB  - An increase of cumulative trauma disorders including carpal tunnel syndrome has
      been seen in the last 10 years. Common causes of carpal tunnel syndrome include
      high-risk occupations, pregnancy, diabetes, and trauma. Measures used to diagnose
      carpal tunnel syndrome are physical examinations, electromyography, computerized
      tomography, and vibrometers. Carpal tunnel syndrome can be treated through
      conservative methods, such as splinting and steroid injection, or through
      surgical procedures. Ergonomic principles can also help to minimize exacerbation
      of symptoms and possibly prevent carpal tunnel syndrome. A case report is used to
      describe the long-term effects of trauma-induced carpal tunnel syndrome and to
      present various therapeutic interventions, including ergonomics, which may be
      useful in returning clients to work. 

PMID- 24441384
TI  - Author indexVolume 5 (1995).

PMID- 24441383
TI  - Assessing the older worker: Are current evaluations valid measurements?
AB  - Older workers that sustain an injury effecting their work performances are
      increasingly being treated by rehabilitation professionals. Often, these persons
      are tested with popular standardized assessment tools that have obtained their
      normative data on young or middle-aged subjects. This article examines the
      normative data relating to some of these assessment tools and the potential
      injustice imposed upon older workers when they are compared to these standards. 

PMID- 24441386
TI  - Volume contentsVolume 5 (1995).

PMID- 24441387
TI  - Epoxidation of stilbene using supported gold nanoparticles: cumyl peroxyl radical
      activation at the gold nanoparticle surface.
AB  - The catalytic epoxidation of cis-stilbene using cumene as a solvent in the
      presence of supported gold nanoparticles (AuNP) yields a mixture of cis and trans
      stilbene oxides. EPR and product distribution studies support a new mechanistic
      proposal where oxygen centred radicals activate the AuNP surface and form active
      surface oxygen species responsible for the epoxidation products. 

PMID- 24441388
TI  - ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and
      renal urate overload.
AB  - Gout is a common disease which results from hyperuricemia. We have reported that
      the dysfunction of urate exporter ABCG2 is the major cause of renal overload
      (ROL) hyperuricemia, but its involvement in renal underexcretion (RUE)
      hyperuricemia, the most prevalent subtype, is not clearly explained so far. In
      this study, the association analysis with 644 hyperuricemia patients and 1,623
      controls in male Japanese revealed that ABCG2 dysfunction significantly increased
      the risk of RUE hyperuricemia as well as overall and ROL hyperuricemia, according
      to the severity of impairment. ABCG2 dysfunction caused renal urate
      underexcretion and induced hyperuricemia even if the renal urate overload was not
      remarkable. These results show that ABCG2 plays physiologically important roles
      in both renal and extra-renal urate excretion mechanisms. Our findings indicate
      the importance of ABCG2 as a promising therapeutic and screening target of
      hyperuricemia and gout. 

PMID- 24441389
TI  - In vitro and in vivo bioactivity assessment of a polylactic acid/hydroxyapatite
      composite for bone regeneration.
AB  - Synthetic bone graft substitutes based on composites consisting of a polymer and
      a calcium-phosphate (CaP) ceramic are developed with the aim to satisfy both
      mechanical and bioactivity requirements for successful bone regeneration. In the
      present study, we have employed extrusion to produce a composite consisting of 50
      wt.% poly(D,L-lactic acid) (PLA) and 50 wt.% nano-sized hydroxyapatite (HA)
      powder, achieving homogeneous distribution of the ceramic within the polymeric
      phase. In vitro, in both a simulated physiological saline (SPS) and a simulated
      body fluid (SBF), a greater weight loss was observed for PLA/HA than for PLA
      particles upon 12-week immersion. Furthermore, in SPS, a continuous release of
      calcium and phosphate from the composite was measured, whereas in SBF, decrease
      of the amount of the two ions in the solution was observed both for PLA and
      PLA/HA accompanied with the formation of a CaP layer on the surface. In vitro
      characterization of the composite bioactivity was performed by culturing human
      mesenchymal stromal cells (hMSCs) and assessing proliferation and osteogenic
      differentiation, with PLA as a control. Both PLA/HA composite and PLA control
      were shown to support hMSCs proliferation over a period of two weeks. In
      addition, the composite significantly enhanced alkaline phosphatase (ALP)
      activity of hMSCs in osteogenic medium as compared with the polymer control. A
      novel implant design was employed to develop implants from dense, extruded
      materials, suitable for testing osteoinductivity in vivo. In a preliminary study
      in dogs, PLA/HA composite implants induced heterotopic bone formation upon 12
      week intramuscular implantation in all animals, in contrast to PLA control, which
      was not osteoinductive. Unlike in vitro, a more pronounced degradation of PLA was
      observed in vivo as compared with PLA/HA composite. 

PMID- 24441390
TI  - Link between aortic valve sclerosis and myocardial no-reflow in ST-segment
      elevation myocardial infarction.
AB  - OBJECTIVE: The"no-reflow" phenomenon is associated with a worse prognosis at
      follow-up for patients with acute ST-segment elevation myocardial infarction
      (STEMI). Predicting and preventing no-reflow is therefore a crucial step in
      improving the prognosis of STEMI patients. The purpose of this study was to
      investigate the association between aortic valve sclerosis (AVS) and myocardial
      no-reflow in patients with STEMI. PATIENTS AND METHODS: Patients with a first
      time diagnosis of STEMI were enrolled consecutively. No-reflow was defined as a
      final TIMI 3 flow with a myocardial blush of grade < 2, temporary epicardial
      coronary no-reflow, and distal coronary occlusion. AVS was defined by
      echocardiography as thickening and calcification of the normal trileaflet aortic
      valve without obstruction to the left ventricular outflow. RESULTS: No-reflow
      developed in 41 patients. In univariate analysis, age, male gender, smoking,
      culprit lesion Syntax score (SX score), and hypertension were significantly
      associated with no-reflow. Multivariate binary logistic regression analyses
      demonstrated age [95 % confidence interval (CI), 1.024-1.096; p=0.001), AVS (95 %
      CI, 1.002-1.100; p=0.039], culprit lesion SX score (95 % CI, 1.08-1.021 p=0.008),
      and symptom-to-balloon time (95 % CI, 1.020-1.097; p=0.002) as independent
      determinants of myocardial no-reflow. CONCLUSION: AVS was significantly and
      independently associated with myocardial no-reflow in STEMI patients.

PMID- 24441391
TI  - Impact of D-dimer level on postinterventional coronary flow and in-hospital MACE
      in ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: Preintervention thrombus burden in the infarct-related artery is an
      independent predictor of no-reflow and adverse outcomes in coronary artery
      disease. The role of D-dimers in the acute phase of ST-elevated myocardial
      infarction (STEMI) during primary percutaneous coronary intervention (PCI) has
      not been fully elucidated. We aimed to investigate the predictive value of serum
      D-dimer levels on the outcome of patients with STEMI. METHODS AND RESULTS: A
      total of 266 consecutive patients presenting with STEMI within the first 12 h of
      symptom onset were included in this study. Patients were divided into two groups
      based on the postinterventional Thrombolysis In Myocardial Infarction (TIMI) flow
      grade score. Postinterventional TIMI grades of 0, 1, or 2 were defined as no
      reflow (group 1) and angiographic success was defined as TIMI 3 flow (group 2). D
      dimer levels were significantly higher in patients with postinterventional no
      reflow than in patients with postinterventional TIMI grade 3 flow (686 +/- 236
      MUg/ml-418 +/- 164 MUg/ml, p < 0.001). Multivariate logistic regression analysis
      showed that D-dimer level was an independent predictor of postinterventional no
      reflow (OR: 1.005; 95 % CI: 1.003-1.007; p < 0.001) and in-hospital major adverse
      cardiovascular events (MACE; OR: 1.002; 95 % CI: 1.000-1.004; p = 0.029).
      Receiver operator characteristics analysis provided a cut-off value of 549 MUg/ml
      for D-dimer for predicting no-reflow with an 83 % sensitivity and an 81 %
      specificity, and 544 MUg/ml for predicting in-hospital MACE with a 69 %
      sensitivity and a 67 % specificity. CONCLUSION: In conclusion, D-dimer levels
      measured on admission may be an independent predictor of no-reflow, which is also
      a predictor of adverse outcomes in patients with STEMI.

PMID- 24441392
TI  - From changes in local RAAS to structural remodeling of the left atrium: A
      beautiful cycle in atrial fibrillation.
AB  - AIMS: In earlier studies, we reported structural remodeling was associated with
      atrial fibrillation (AF) and showed that the renin-angiotensin-aldosterone system
      (RAAS) was linked to AF. It is reasonable to hypothesize that there is a cycle,
      from RAAS to structural remodeling to AF. PATIENTS AND METHODS: Our study group
      consisted of 80 patients scheduled for mitral valve replacement surgery. Tissue
      samples of the left atrial appendages were obtained. Masson's trichrome staining
      and immunohistochemical staining were performed to assess the extent of fibrosis.
      Radioimmunoassay was carried out to investigate the expression levels of local
      RAAS. RAAS-related genes were analyzed by RT-PCR. RESULTS: There was a
      significantly increased degree of fibrosis in AF patients compared with sinus
      rhythm (SR) patients (p = 0.023). There were significant differences in the
      expression levels of local angiotensin (Ang) II between the SR and the AF groups
      (p = 0.002). The expression levels of local Ang II correlated with the duration
      of AF (r = 0.727851, p = 0.001) and with collagen type I (r = 0.672189, p =
      0.032). In the AF group, the mRNA expressions of the AT1R and ACE genes were
      markedly up-regulated in comparison with the SR group (p = 0.021 and p = 0.037).
      CONCLUSIONS: On the basis of this study, and in combination with results of our
      previous studies, we demonstrate for the first time that there is a cycle
      involving RAAS, structural remodeling, and AF. RAAS, structural remodeling, and
      AF are the principal aspects in this cycle.

PMID- 24441393
TI  - Acute myocardial infarction after a gunshot wound.

PMID- 24441394
TI  - Terminal QRS distortion and severity of coronary artery disease in ST-elevation
      myocardial infarction.
AB  - BACKGROUND: Grade 3 ischemia (G3I) is defined as ST elevation with distortion of
      the terminal portion of the QRS complex on electrocardiograms (ECGs) of patients
      with ST-segment elevation myocardial infarction (STEMI). Although the association
      between G3I and short- and long-term cardiovascular events is well established,
      its mechanism is unclear. We assessed the association between G3I on the
      admission ECG and SYNTAX score (SS) in patients with STEMI undergoing primary
      percutaneous coronary intervention. PATIENTS AND METHODS: The study population
      consisted of 312 patients with STEMI. Baseline ECGs of the patients were analyzed
      for grade of ischemia; the online latest updated version (2.11) of the SS
      calculator was used to determine the SS (http://www.syntaxscore.com). Patients
      were divided into two groups according to their grade of ischemia: grade 2
      ischemia (G2I) or G3I. Also, patients were classified according to their SS as SS
      < 22 (low) or SS >= 22 (high). RESULTS: There were 211 patients in the low SS
      group and 101 patients in the high SS group. G3I was present in 31.1 % (n = 97)
      of the study population. SS was significantly higher in patients with G3I than in
      patients with G2I (20.1 +/- 8.8 vs. 13.7 +/- 7.1, p < 0.001). G3I was
      significantly higher in patients with high SS (50.5 % vs. 21.8 %, p < 0.001).
      Multivariate logistic regression analysis revealed that G3I (p < 0.001), diabetes
      (p = 0.013), age (p = 0.016), and anterior MI (p = 0.011), were independent
      predictors of high SS. CONCLUSION: In conclusion, G3I was independently related
      to high SS. We suggest that elevated SS in patients with G3I may explain the
      relationship between G3I and the poor outcome observed in these patients.
      Furthermore, the prediction of high SS by means of G3I in patients with STEMI may
      help determine the most appropriate revascularization method and prevent
      procedure failure.

PMID- 24441395
TI  - [Individualization of exercise load control for inpatient cardiac rehabilitation.
      Development and evaluation of a HRV-based intervention program for patients with
      ischemic heart failure].
AB  - BACKGROUND: The effective use of rehabilitation programs is of primary importance
      in order to improve the physical performance of cardiac disease patients. A
      modular program has been developed which is intended to structure and
      individualize conventional, exercise-based rehabilitation programs according to
      the individual needs and physical condition of each patient. The
      individualization of the program is based on detailed diagnostics before patients
      enter the program and daily measurements of heart rate variability (HRV) during
      cardiac rehabilitation. METHODS: A total of 30 patients with ischemic heart
      disease were randomly assigned either to the intervention group (IG), completing
      the modular individualized rehabilitation program [n=15, mean age 54.4+/-4.2
      years and mean left ventricular ejection fraction (LVEF) 28.53+/-6.25%) or to the
      control group (CG) taking part in the conventional rehabilitation program (n=15,
      mean age 56.4+/-4.4 years and mean LVEF 27.63+/-5.62). Before and after the
      intervention, cardiorespiratory fitness was assessed by measurement of maximal
      oxygen consumption (relative VO2max) during bicycle ergometry and the 6-minute
      walk test (6-MWT). Pre-post comparisons of cardiorespiratory fitness indicators
      were used to evaluate the effectiveness of the rehabilitation program. In
      addition to the results of the basic clinical investigations and the
      cardiorespiratory testing, results of standardized HRV measurements of 10 min at
      morning rest served as criteria for program individualization. RESULTS: The
      relative VO2max increased significantly (p<0.05) in the IG whereas no change was
      found in the CG. Similar results were found for maximum power output during
      bicycle ergometry (p<0.01) and for 6-MWT distance (p<0.001). Although patients in
      the IG completed less aerobic exercise sessions than those in the CG (p<0.001)
      the physical performance of the IG improved significantly. DISCUSSION: The
      results prove the effectiveness and efficacy of the modular individualized
      rehabilitation program. They further suggest the need for an individual program
      matrix instead of a maximum performance matrix in cardiac rehabilitation.
      Individualization should be based on clinical and performance diagnostics before
      and accompanying assessments of training condition, e.g. by HRV measurements,
      during rehabilitation programs. Each patient should only perform those
      intervention programs which match the results of the basic clinical investigation
      and additional analyses during rehabilitation.

PMID- 24441396
TI  - Role of anticardiolipin antibodies in the pathogenesis of prosthetic valve
      thrombosis: An observational study.
AB  - BACKGROUND: Prosthetic valve thrombosis (PVT) is serious complication of valvular
      replacement surgery, and increased levels of anticardiolipin antibodies (aCL) are
      associated with thrombosis. The aim of this study was to evaluate the role of aCL
      in the development of PVT. PATIENTS AND METHODS: We studied the aCL IgM and IgG
      levels in 114 patients with PVT and 80 healthy patients with prosthetic valves
      without PVT or a history of thrombosis. All patients underwent detailed
      transthoracic, transesophageal echocardiographic and clinical examinations. Blood
      samples were obtained after transesophageal echocardiography. Tests were repeated
      12 weeks apart in patients with aCL IgM or IgG positivity. RESULTS: The mean age,
      sex, presence of atrial fibrillation and cardiovascular risk factors, elapsed
      time after surgery, and prosthetic valve type and location were similar between
      patients with PVT and those without. Ineffective anticoagulation was
      significantly higher among patients with PVT (p < 0.001). The aCL IgM values were
      significantly higher and positive (> 40 MPL) in the PVT group compared with the
      control group (10.58 +/- 15.90 MPL to 3.70 +/- 2.30 MPL, p < 0.001; 7.0 to 0 %, p
      = 0.016, respectively). The aCL IgG values were significantly higher and positive
      (> 40 GPL) in the PVT group compared with the control group (12.04 +/- 17.58 GPL
      to 3.83 +/- 2.56 GPL, p < 0.001 and 7.9 to 0 %, p = 0.01, respectively).
      According to international consensus documents, 16 patients had antiphospholipid
      syndrome. Ineffective anticoagulation and aCL IgM and IgG positivity were
      independent predictors of PVT in logistic regression analysis (multivariate r(2)=
      0.648; p < 0.001, OR= 21.405, 95 %CI= 8.201-55.872; p = 0.008, OR= 1.322, % 95CI=
      1.076-1.626; p = 0.005, OR= 1.288, 95 %CI= 1.079-1.538). CONCLUSION: Since the
      presence of aCL IgM and IgG positivity may cause a tendency toward PVT, these
      values should be examined in all patients with PVT.

PMID- 24441397
TI  - Pyoderma gangrenosum-like skin changes after subcutaneous administration of low
      molecular weight heparin.
AB  - In the present report, we would like to comment a case of patient with diabetes
      mellitus type 2 manifesting the rare complication of heparin subcutaneous
      administration in a form of pyoderma gangrenosum-like skin changes which were
      induced probably by an immune-modulating activity of heparin. 

PMID- 24441398
TI  - Multifunctional aptamer-miRNA conjugates for targeted cancer therapy.
AB  - While microRNAs (miRNAs) clearly regulate multiple pathways integral to disease
      development and progression, the lack of safe and reliable means for specific
      delivery of miRNAs to target tissues represents a major obstacle to their broad
      therapeutic application. Our objective was to explore the use of nucleic acid
      aptamers as carriers for cell-targeted delivery of a miRNA with tumor suppressor
      function, let-7g. Using an aptamer that binds to and antagonizes the oncogenic
      receptor tyrosine kinase Axl (GL21.T), here we describe the development of
      aptamer-miRNA conjugates as multifunctional molecules that inhibit the growth of
      Axl-expressing tumors. We conjugated the let-7g miRNA to GL21.T and demonstrate
      selective delivery to target cells, processing by the RNA interference machinery,
      and silencing of let-7g target genes. Importantly, the multifunctional conjugate
      reduced tumor growth in a xenograft model of lung adenocarcinoma. Therefore, our
      data establish aptamer-miRNA conjugates as a novel tool for targeted delivery of
      miRNAs with therapeutic potential. 

PMID- 24441401
TI  - Guest Editors' note.

PMID- 24441400
TI  - Elevated risk from estrogens in the Yodo River basin (Japan) in winter and
      ozonation as a management option.
AB  - A simple model was set up to predict estrogen concentrations and endocrine
      disruption risk in the Yodo River, Japan. This catchment spans the conurbations
      of Kyoto and Osaka and is the main source of drinking water for Osaka City,
      Japan. From the river survey data (5 separate occasions between 2005 and 2008), a
      maximum of 32 g per day estrone (E1) load was observed in the most downstream
      site of the river. Predicted E1 concentrations were in reasonable agreement with
      the measurements taken at several points within the basin from a series of
      sampling campaigns. The predicted concentrations exceeded a net estradiol (E2)
      equivalent of 1 ng L(-1) on only a few occasions, suggesting that only limited
      endocrine disruption phenomena in fish along the Yodo River is likely. The model
      was then used to examine the impact on estrogen concentrations and endocrine
      disruption of a number of different scenarios. It was found that in-river
      biodegradation had little effect on predicted concentrations and the outcome of
      endocrine disruption along the catchment. However, reduced sewage treatment
      removal, as can be experienced in winter in Japan, led to levels of 3.1 ng L(-1)
      E2 equivalents being possible. The reduced river flow in winter in Japan
      exacerbates the situation as it offers less dilution. It was found that the
      application of the ozonation process as a tertiary sewage treatment in winter
      could prevent this higher risk endocrine disruption situation. 

PMID- 24441399
TI  - Uncovering and dissecting the genotoxicity of self-inactivating lentiviral
      vectors in vivo.
AB  - Self-inactivating (SIN) lentiviral vectors (LV) have an excellent therapeutic
      potential as demonstrated in preclinical studies and clinical trials. However,
      weaker mechanisms of insertional mutagenesis could still pose a significant risk
      in clinical applications. Taking advantage of novel in vivo genotoxicity assays,
      we tested a battery of LV constructs, including some with clinically relevant
      designs, and found that oncogene activation by promoter insertion is the most
      powerful mechanism of early vector-induced oncogenesis. SIN LVs disabled in their
      capacity to activate oncogenes by promoter insertion were less genotoxic and
      induced tumors by enhancer-mediated activation of oncogenes with efficiency that
      was proportional to the strength of the promoter used. On the other hand, when
      enhancer activity was reduced by using moderate promoters, oncogenesis by
      inactivation of tumor suppressor gene was revealed. This mechanism becomes
      predominant when the enhancer activity of the internal promoter is shielded by
      the presence of a synthetic chromatin insulator cassette. Our data provide both
      mechanistic insights and quantitative readouts of vector-mediated genotoxicity,
      allowing a relative ranking of different vectors according to these features, and
      inform current and future choices of vector design with increasing biosafety. 

PMID- 24441402
TI  - Increasing client involvement in vocational rehabilitation: an expectations-based
      approach to assessment and planning.
AB  - The article provides a rationale for according greater attention to the
      expectations of vocational rehabilitation (VR) clients. Based on counseling
      theory, rehabilitation philosophy, federal regulatory mandates, and counseling
      process and outcome studies, the authors' thesis is that an expectations-based
      approach to rehabilitation counseling will increase client involvement in all
      phases of the VR process. 

PMID- 24441403
TI  - Career development theory as a framework for assessment and planning in clubhouse
      based transitional employment programs for people with psychiatric disabilities.
AB  - This article describes assessment and career planning in programs using the
      clubhouse model of psychiatric rehabilitation and relates clubhouse practice to
      career development theory. Career development theory provides a useful framework
      to explain clubhouse assessment methodologies and the role of transitional
      employment in rehabilitation practice. This article also suggests practice
      improvements and areas for further research. 

PMID- 24441404
TI  - Correlates of work interference scores on the MMPI-2 among participants in
      residential substance abuse treatment.
AB  - The article describes a concurrent prediction of Work Interference scores on the
      MMPI-2 with a sample (N = 82) of participants in a court-mandated residential
      substance abuse treatment facility. Anxiety and Low Self-Esteem were
      significantly related to Work Interference (R = 0.80, P < 0.0001). Implications
      for administrative policy, counseling practice, and future research are
      discussed. 

PMID- 24441405
TI  - The role of self-efficacy and locus of control in job readiness training
      programs.
AB  - Research suggests that individuals with higher levels of self-efficacy and
      internal locus of control are more likely to engage in job search activities and
      persist for longer periods of time when faced with repeated failure when compared
      to individuals with low self-efficacy and external locus of control (Kulik and
      Rowland, J. Organization. Behav. 1989;10:361-367). This article will discuss how
      Bandura's (Psychol. Rev. 1977;84:191-214) self-efficacy theory and Rotter's
      (Psychol. Monogr.: Gen. Appl. 1966;80:1-27) locus of control theory can be
      applied to increase participation and persistence in job readiness training
      programs for people with disabilities. The authors will provide an overview of
      those theories and then use a case example to illustrate how they can be used in
      the job readiness process. 

PMID- 24441406
TI  - Job retention and breast cancer: employee perspectives and implications for
      rehabilitation planning.
AB  - The article presents four case studies of employed women who have had breast
      cancer. Specifically, the authors examine respondents' career maintenance
      concerns in the areas of (a) worksite accessibility, (b) performance of essential
      job functions, (c) job mastery, and (d) job satisfaction. Post-employment
      strategies are presented to assist rehabilitation professionals in meeting the on
      the-job needs of women with breast cancer. 

PMID- 24441407
TI  - Planning strategies in disability management.
AB  - Successful disability management practice is a systemic approach to vocational
      rehabilitation that begins with planning at the organizational level. A strategic
      planning format is used to outline the basic tenets of planning and, through its
      description, describe the unique approach to workplace intervention disability
      management has to offer. A case study is used to illustrate a simple application
      of planning steps of needs assessment, establishing goals and objectives, and
      developing disability management strategies. 

PMID- 24441408
TI  - Future trends in assessment and planning: priorities for vocational
      rehabilitation in the 21st century.
AB  - The article examines the current status and future directions of assessment and
      planning in vocational rehabilitation (VR). Major themes include (a) the
      increasing emphasis on consumer involvement, (b) career development as the
      ultimate goal of the VR process, (c) integrative assessment of the 'whole'
      person, (d) employers as partners in planning and service delivery, and (e) the
      expanding role of rehabilitation counselors in a highly diversified professional
      marketplace. 

PMID- 24441409
TI  - Social origins and implications of child labor.
AB  - Child labor continues to present a serious health threat to millions of children
      worldwide. Not all work is detrimental to children, and under carefully
      controlled conditions can benefit them in terms of physical and intellectual
      development as well as make positive contributions to their financial status.
      Unfortunately, most situations where children are used as a labor force are not
      designed with the health of the laborers as a primary concern. This article will
      review the current status of child labor, present theories regarding the social,
      cultural and economic bases of the practice, discuss its health implications and
      finally, explore possible solutions to this complex problem. 

PMID- 24441411
TI  - Author indexVolume 10 (1998).

PMID- 24441410
TI  - Ergonomics and education: fad, failure or fraction of back injury prevention?
AB  - Ergonomics, in the traditional definition, is the science of design of work sites
      and work methods which influence production performance. In recent years, worker
      complaints and reports of injuries have caused evaluation of the effect of work
      stressors on workers. Currently, the rehabilitation specialist plays a pivotal
      role in both prevention and management of physical work related complaints.
      Rehabilitation ergonomic practitioners combine a scientific background in
      function and pathology with the act of developing preventive or restorative
      remedies. A volunteer group of sixteen rehabilitation professionals who utilize
      ergonomic principles in the workplace developed a document, identifying job
      functions of the newly defined field. This paper presents philosophy and a model
      for educational development and potential credentialing areas for rehabilitation
      ergonomists. 

PMID- 24441413
TI  - Volume contentsVolume 10 (1998).

PMID- 24441415
TI  - New nitrogenous bisabolene-type sesquiterpenes from a formosan sponge Axinyssa
      sp.
AB  - Chemical investigation of a Formosan sponge Axinyssa sp. has led to the isolation
      of five nitrogenous bisabolene-type sesquiterpenes 1-5, including two new
      compounds axinysalines A (1) and B (2). The structures of new compounds were
      elucidated by analysis of high resolution (HR)-MS and two dimensional (2D)-NMR
      spectra and comparison of its NMR data with those of known analogues. Compound 1
      exhibited moderate to weak cytotoxicity against Molt 4 and K562 cancer cell
      lines. 

PMID- 24441414
TI  - MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival
      and ameliorates the autophagic flux defect in a mouse model of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder
      caused by selective motor neuron degeneration. Abnormal protein aggregation and
      impaired protein degradation pathways may contribute to the disease pathogenesis.
      Although it has been reported that autophagy is altered in patients and animal
      model of ALS, little is known about the role of autophagy in motor neuron
      degeneration in this disease. Our previous study shows that rapamycin, an MTOR
      dependent autophagic activator, accelerates disease progression in the SOD1(G93A)
      mouse model of ALS. In the present report, we have assessed the role of the MTOR
      independent autophagic pathway in ALS by determining the effect of the MTOR
      independent autophagic inducer trehalose on disease onset and progression, and on
      motor neuron degeneration in SOD1(G93A) mice. We have found that trehalose
      significantly delays disease onset prolongs life span, and reduces motor neuron
      loss in the spinal cord of SOD1(G93A) mice. Most importantly, we have documented
      that trehalose decreases SOD1 and SQSTM1/p62 aggregation, reduces ubiquitinated
      protein accumulation, and improves autophagic flux in the motor neurons of
      SOD1(G93A) mice. Moreover, we have demonstrated that trehalose can reduce
      skeletal muscle denervation, protect mitochondria, and inhibit the proapoptotic
      pathway in SOD1(G93A) mice. Collectively, our study indicated that the MTOR
      independent autophagic inducer trehalose is neuroprotective in the ALS model and
      autophagosome-lysosome fusion is a possible therapeutic target for the treatment
      of ALS. 

PMID- 24441416
TI  - Measurements of normal joint angles by goniometry in calves.
AB  - OBJECTIVE: The aim of this study was to establish normal reference values of the
      forelimb and hindlimb joint angles in normal Holstein calves. METHODS: Thirty
      clinically normal Holstein calves that were free of any detectable
      musculoskeletal abnormalities were included in the study. A standard transparent
      plastic goniometer was used to measure maximum flexion, maximum extension, and
      range-of-motion of the shoulder, elbow, carpal, hip, stifle, and tarsal joints.
      The goniometric measurements were done on awake calves that were positioned in
      lateral recumbency. The goniometric values were measured and recorded by two
      independent investigators. RESULTS: As a result of the study it was concluded
      that goniometric values obtained from awake calves in lateral recumbency were
      found to be highly consistent and accurate between investigators (p <0.05).
      CLINICAL SIGNIFICANCE: The data of this study acquired objective and useful
      information on the normal forelimb and hindlimb joint angles in normal Holstein
      calves. Further studies can be done to predict detailed goniometric values from
      different diseases and compare them.

PMID- 24441417
TI  - Observations on transition metal free biaryl coupling: potassium tert-butoxide
      alone promotes the reaction without diamine or phenanthroline catalysts.
AB  - Biaryl coupling (often labelled 'C-H activation') of aromatic systems can be
      achieved by potassium tert-butoxide alone in the absence of any amine or
      bipyridine catalyst (1,10-phenanthroline or N,N'-dimethylethylenediamine being
      the most common), previously reported to be essential. Various mechanistic
      studies and observations are presented which suggest that when 1,10
      phenanthroline is employed as the catalyst, the alkoxide is destroyed almost
      immediately. 

PMID- 24441418
TI  - Preventing dementia: how lifestyle in midlife affects risk.
AB  - PURPOSE OF REVIEW: Dementia is a worldwide health priority, with increasing
      public health burden and thus need for preventive strategies. Although many
      associations are proposed, there has been lack of sufficient evidence or
      demonstration of modifiability. This review will discuss the methodological
      challenges and the most established, controversial and novel modifiable midlife
      risk factors. RECENT FINDINGS: There has been a shift towards a life-course
      approach, with large cohort longitudinal studies helping to untangle 'windows of
      opportunity' or reverse causation with vascular factors (hypertension and BMI),
      hormone replacement therapy and depression. Other vascular factors, such as
      hyperglycaemia, have now been approached as a continuum and BMI/alcohol as U
      shaped associations. There is evidence regarding associations or mechanisms for
      personality, insomnia, cognitive stimulation and social activities, head injury,
      diet, and reproductive and oral health. Environmental considerations such as
      passive smoke, noise and hygiene exposure are also explored. SUMMARY: Increasing
      evidence of associations from midlife will guide the shift to interventional
      studies from the midlife period. However, research challenges are such that the
      ideal studies may be impossible, although, for numerous factors, it has been
      argued that other known adverse health effects justify initiating or continuing
      health interventions in the absence of this evidence.

PMID- 24441419
TI  - Intellectual disability as a disorder of reasoning and judgement: the gradual
      move away from intelligence quotient-ceilings.
AB  - PURPOSE OF REVIEW: Adoption of the term intellectual disability (intellectual
      developmental disorder, IDD) in DSM-5 represents a shift from a disability (test
      score) emphasis to a disorder (medical/neurobiological) emphasis. Several
      implications of this shift for definition and diagnosis of intellectual
      disability (ID) are discussed. RECENT FINDINGS: The intellectual disability (IDD)
      section of DSM-5 reflects a growing concern about excessive and inappropriate
      reliance on intelligence quotient (IQ) cut-offs. Clinicians are now encouraged to
      take into account various sources of test error; rely more on neuropsychological
      profiles of cognitive impairments; and approach the adaptive functioning of
      patients with a greater emphasis on cognitive aspects, such as risk-unawareness.
      SUMMARY: A psychometric approach to intellectual disability/IDD, defining it
      solely in terms of test scores, is inappropriate for psychiatric and medical
      disorders, which use a disorder rather than a disability model. The intellectual
      disability/IDD section in DSM-5 is the first prototypical attempt to broaden the
      category, and approach it in more clinical terms, while still maintaining the
      meaning of the condition.

PMID- 24441420
TI  - Update on diagnostic classification in autism.
AB  - PURPOSE OF REVIEW: In the lead up to and following the recent publication of the
      DSM-5, the diagnostic construct of autism has received intense scrutiny. RECENT
      FINDINGS: This article briefly reviews the history of the diagnosis of autism,
      the changes that have occurred in the diagnosis over time, and the rationale for
      change. The most significant changes being introduced with the DSM-5 are
      highlighted, as well as some of the concerns that will be a focus of attention
      with respect to the potential impacts going forward. SUMMARY: The categorical
      divisions that characterized the pervasive developmental disorders are now
      collapsed into a single entity, autism spectrum disorder. The final DSM-5
      criteria have yet to be formally compared prospectively against prior criteria,
      but early indications suggest that the boundaries around the pervasive
      developmental disorders have not been substantially altered.

PMID- 24441421
TI  - Psychiatric disorders in people with intellectual disability (intellectual
      developmental disorder): forensic aspects.
AB  - PURPOSE OF THE REVIEW: Persons with intellectual disability come into frequent
      and underreported contact with the legal system. Advances in forensic psychiatry
      help better identify persons with intellectual disability in forensic contexts,
      inform evaluation and treatment, and elucidate unique characteristics of this
      population. With the release of Diagnostic and Statistical Manual of Mental
      Disorders (DSM-5), forensic psychiatrists must adjust to changes in the
      diagnostic process. RECENT FINDINGS: This review examines the past year's
      contributions to the literature, including predictors among offenders with
      intellectual disability, concurrent diagnoses, efficacy of competence
      restoration, means of studying individuals with intellectual disability, and
      impact of DSM-5. SUMMARY: Impoverished personal relationships are found to be an
      important predictor of offense among persons with intellectual disability. A
      Personality Disorder Characteristics Checklist allows screening for personality
      disorders (indicative of increased risk of violence) among intellectual
      disability offenders. Referrals to specialists for treatment more often occur for
      violent and sexual offenses than for other offenses. Competence restoration is
      historically low among those with intellectual disability, specially compared
      with those referred for substance abuse and personality disorders. However, the
      Slater Method results in higher rates of restoration than traditional training
      methods. DSM-5 alters the definition of intellectual disability, moving from an
      IQ-oriented diagnosis system to a multifaceted approach, introducing more
      flexibility and nuance.

PMID- 24441422
TI  - New classification for neurodevelopmental disorders in DSM-5.

PMID- 24441424
TI  - From the editor.

PMID- 24441425
TI  - The role of the rehabilitation placement professional in the ADA era.
AB  - Rehabilitation placement professionals have a vital role in helping American
      corporations develop recruiting, hiring, and accommodation practices that are
      compatible with the civil rights protections in the Americans with Disabilities
      Act (ADA). To perform this consulting function, they must have current
      information on: (a) provisions and protections in Title I of the ADA; (b) the
      benefits of hiring people with disabilities; (c) the cost-effectiveness of
      reasonable accommodations; and (d) collaborative employer/employee approaches to
      job accommodations. 

PMID- 24441426
TI  - Physical and mental practices of music students as they relate to the occurrence
      of music-related injuries.
AB  - OBJECTIVE: The purpose of this study was two-fold: To obtain descriptive
      information regarding general physical and mental habits of music students and to
      ascertain if there are any associations between specific daily activities or
      habits and the appearances of these injuries. STUDY DESIGN: Questionnaires were
      distributed to three hundred music students at Boston University. Of the 45
      respondents, 19 students were willing to participate in an interview. Descriptive
      statistics were analyzed and comparisons were made to a similar study which was
      conducted at New England Conservatory in Boston, Massachusetts (Hagglund, K.,
      Unpublished study, 1994). RESULTS: The results suggest that Boston University
      music students follow expected trends reported in previous research (Fishbein and
      Middlestadt, 1988; Manchester and Fielder, 1991; Hagglund, 1994). Eighty two
      percent (n=37) of the respondents were performance majors and the majority of
      them began playing their instrument at age 10. Out of the 45 respondents, 28 were
      female of whom 68% (n=19) reported having a music-related injury. Of the
      remaining 17 males, 53% (n=9) reported also having a music-related injury.
      Sophomores and juniors accounted for 15 (54%) of the total 28 musicians with
      injuries in this study. The typical practice habits that were described by the
      respondents included 2 h sessions, with 10-15 min breaks each hour. Most
      musicians disclosed to occasionally playing their instruments even when
      experiencing pain. RESULTS from this study suggest that as the hours spent
      playing increased, so did the incidence of injury. Medical attention from
      neurologists, general practitioners, performing arts specialists and
      laryngologists was pursued by 18 (64%) of the 28 injured musicians. Sixty-one
      percent of the respondents with injuries saw more than one rehabilitation
      specialists, including physical therapists (50%); Alexander/Feldenkrais teachers
      (44%) and massage therapists (28%). More than one treatment method was given to
      74% of the injured. These treatment methods included methods such as: Altering
      posture, habits or playing technique, exercise and stretching, rest, ice and
      massage. Satisfaction in career and the ability to live up to self expectations
      was high, while performance anxiety was not bothersome for 82% of the
      respondents. Fifty-two percent reported reacting well to stress and 44% described
      having an average level of self-consciousness. Most respondents (89%)
      participated in some type of physical fitness, most exercising either one (30%)
      or three (23%) days a week, and 75% reported that they stretch prior to playing.
      CONCLUSION: This study provides information on the general habits of music
      studtents which can be beneficial to rehabilitation specialists, as well as other
      medical professionals treating musicians. By understanding the lifestyles and
      dynamics of being a musician, rehabilitation specialists can devise better
      individualized intervention and preventative strategies. Unfortunately, musicians
      remain uninformed on the current treatments, rehabilitation approaches, and most
      importantly the predisposing and preventative factors of music-related injuries.
      Occupational therapists, physical therapists and other rehabilitation specialists
      can and should be the professionals to provide guidance to the population of
      musicians on the above mentioned factors.

PMID- 24441427
TI  - The ergonomics of child care: conducting worksite analyses.
AB  - This paper examined the ergonomics of child care at a large metropolitan,
      university-based child care center. A case study approach was used to describe
      the job analysis process and results. Center staff were involved in the
      identification of health risk factors by completing an ergonomics survey and
      responding to questions posed during the job analysis (n=36). Two occupational
      therapists analyzed six different rooms, accommodating different age groups of
      children. Specific activities were identified as stressors and/or health risk
      factors inherent in the jobs according to the age of the children cared for. A
      list of ergonomic health risk factors and recommendations was generated. 

PMID- 24441423
TI  - Autophagy is essential for cardiac morphogenesis during vertebrate development.
AB  - Genetic analyses indicate that autophagy, an evolutionarily conserved lysosomal
      degradation pathway, is essential for eukaryotic differentiation and development.
      However, little is known about whether autophagy contributes to morphogenesis
      during embryogenesis. To address this question, we examined the role of autophagy
      in the early development of zebrafish, a model organism for studying vertebrate
      tissue and organ morphogenesis. Using zebrafish that transgenically express the
      fluorescent autophagy reporter protein, GFP-LC3, we found that autophagy is
      active in multiple tissues, including the heart, during the embryonic period.
      Inhibition of autophagy by morpholino knockdown of essential autophagy genes
      (including atg5, atg7, and becn1) resulted in defects in morphogenesis, increased
      numbers of dead cells, abnormal heart structure, and reduced organismal survival.
      Further analyses of cardiac development in autophagy-deficient zebrafish revealed
      defects in cardiac looping, abnormal chamber morphology, aberrant valve
      development, and ectopic expression of critical transcription factors including
      foxn4, tbx5, and tbx2. Consistent with these results, Atg5-deficient mice
      displayed abnormal Tbx2 expression and defects in valve development and chamber
      septation. Thus, autophagy plays an essential, conserved role in cardiac
      morphogenesis during vertebrate development. 

PMID- 24441428
TI  - Rheumatoid arthritis and household work limitations in women.
AB  - The purpose of this article is to examine the impact of rheumatoid arthritis (RA)
      on a woman's capacity to perform household work. Household work involves both
      instrumental functions (e.g., cooking, cleaning, shopping) and nurturant
      functions (e.g., caring for children, listening and comforting). This article
      includes a review of the relevant literature, an interview with a rheumatologist,
      and case studies of two women with RA. The literature suggests that household
      work limitations exist in women with RA, especially those women with more severe
      RA; and that the patient may benefit from appropriate social support and ongoing
      treatment and education. 

PMID- 24441429
TI  - Recommendations for working with interpreters.
AB  - With the steady increase of non-English-speaking immigrants such as Hispanics in
      the U.S. over the last 15 years, the need for interpreters in medical settings
      has grown. However, health care practitioners such as occupational therapists and
      physical therapists receive minimal training in working with interpreters. This
      paper provides the reader with recommendations for working with interpreters and
      for when an interpreter is not available. In addition, a case example
      illustrating common problems that may arise when working with an interpreter and
      some solutions are discussed. Further, the simultaneous and consecutive methods
      of interpreting are compared; and the difference between interpreters and
      translators is discussed. 

PMID- 24441430
TI  - The ADA offers unique opportunities for physical and occupational therapists.
AB  - With the advent of the Americans with Disabilities Act, physical and occupational
      therapists have an opportunity to expand their role in working with disabled
      individuals, specifically in the areas of employment, public accommodations and
      transportation. This paper will discuss the commonality in minimizing the
      disabling effects of physical disabilities and integrating the disabled into the
      mainstream of life. It is evident that the ADA presents unique opportunities for
      therapists. Effective implementation of the law can be accomplished when physical
      and occupational therapists are involved. 

PMID- 24441431
TI  - The role of occupational therapy in the transition from school to work for
      adolescents with disabilities.
AB  - Through the use of a literature review, this article will examine the evolution
      of the transition from the school room to the workplace for adolescents with
      developmental disabilities. It will explain an ideal occupational therapy program
      based on a current model used with this transition and demonstrate how
      occupational therapy can benefit the student during this phase of his/her life. A
      case study will be cited to describe how a combination of current programs and
      occupational therapy can be implemented. 

PMID- 24441432
TI  - Cultural sensitivity: integrating cultural concepts into clinical practice.
AB  - This paper draws insight from an assorted compilation of health care literature
      for the purpose of attaining a comprehensive perspective on issues encountered by
      health care professionals working with a culturally diverse clientele. The
      primary intent of this article is to provide clinically useful information geared
      toward enhancing quality health care services for people of various cultural
      backgrounds. Definition of difficulties experienced by practitioners and clients,
      as well as practical suggestions which may reduce ineffective treatment methods
      and increase successful treatment outcomes for individuals from diverse cultural
      identities are discussed. Deliberation of cultural issues will be limited to the
      African-American, Anglo-American, Asian, Hispanic and Native American Indian
      cultures. 

PMID- 24441433
TI  - Carbon nanotube-copper exhibiting metal-like thermal conductivity and silicon
      like thermal expansion for efficient cooling of electronics.
AB  - Increasing functional complexity and dimensional compactness of electronic
      devices have led to progressively higher power dissipation, mainly in the form of
      heat. Overheating of semiconductor-based electronics has been the primary reason
      for their failure. Such failures originate at the interface of the heat sink
      (commonly Cu and Al) and the substrate (silicon) due to the large mismatch in
      thermal expansion coefficients (~300%) of metals and silicon. Therefore, the
      effective cooling of such electronics demands a material with both high thermal
      conductivity and a similar coefficient of thermal expansion (CTE) to silicon.
      Addressing this demand, we have developed a carbon nanotube-copper (CNT-Cu)
      composite with high metallic thermal conductivity (395 W m(-1) K(-1)) and a low,
      silicon-like CTE (5.0 ppm K(-1)). The thermal conductivity was identical to that
      of Cu (400 W m(-1) K(-1)) and higher than those of most metals (Ti, Al, Au).
      Importantly, the CTE mismatch between CNT-Cu and silicon was only ~10%, meaning
      an excellent compatibility. The seamless integration of CNTs and Cu was achieved
      through a unique two-stage electrodeposition approach to create an extensive and
      continuous interface between the Cu and CNTs. This allowed for thermal
      contributions from both Cu and CNTs, resulting in high thermal conductivity.
      Simultaneously, the high volume fraction of CNTs balanced the thermal expansion
      of Cu, accounting for the low CTE of the CNT-Cu composite. The experimental
      observations were in good quantitative concurrence with the theoretically
      described 'matrix-bubble' model. Further, we demonstrated identical in-situ
      thermal strain behaviour of the CNT-Cu composite to Si-based dielectrics, thereby
      generating the least interfacial thermal strain. This unique combination of
      properties places CNT-Cu as an isolated spot in an Ashby map of thermal
      conductivity and CTE. Finally, the CNT-Cu composite exhibited the greatest
      stability to temperature as indicated by its low thermal distortion parameter
      (TDP). Thus, this material presents a viable and efficient alternative to
      existing materials for thermal management in electronics. 

PMID- 24441434
TI  - Tibial baseplate fracture associated with polyethylene wear and osteolysis after
      total knee arthroplasty.
AB  - INTRODUCTION: Fracture of the tibial baseplate following total knee arthroplasty
      is very rare given the developments in modern prosthesis design. Tibial baseplate
      fracture secondary to polyethylene wear, osteolysis and component malalignment in
      an elderly obese patient is reported in the present article. PRESENTATION OF
      CASE: A 69-year-old woman had undergone total knee arthroplasty eleven years
      prior to presentation and reported nine months of chronic pain, which was caused
      by a neglected fracture of the baseplate. DISCUSSION: We discuss the prevention
      of implant fracture after total knee arthroplasty and address the risk factors
      associated with this complication. CONCLUSION: The present case emphasizes the
      importance of properly informing patients and encouraging them to report such
      complaints immediately to allow for early revision and prevention of component
      fracture, especially in patients with risk factors such as obesity and component,
      malalignment.

PMID- 24441436
TI  - Laparoscopic sleeve gastrectomy with loop bipartition: A novel metabolic
      operation in treating obese type II diabetes mellitus.
AB  - INTRODUCTION: We report the first case of laparoscopic sleeve gastrectomy with
      loop bipartition (a modified form of Santoro's operation) in the treatment of
      type II diabetes mellitus associated with obesity. PRESENTATION OF CASE: A 46
      year-old gentleman (baseline BMI 32.9; BW 98.5kg) with 7-year history of type II
      diabetes mellitus (DM) underwent the procedure in Hong Kong. The control of DM
      was poor even with intensive medical therapy before the operation. Standard
      laparoscopic sleeve gastrectomy (SG) was performed and a loop gastroileostomy was
      fashioned at the antrum 250cm from the ilececal valve without division of the 1st
      part of duodenum after SG. The resultant gastric tube has two outlets, one to the
      first part of duodenum and the other to the ileum with preferential passage of
      food through the gastroileostomy as shown on subsequent contrast study. The
      patient's recovery was uneventful. The excess BMI loss was 97% with complete
      normalization of all metabolic parameters at 1-year follow-up. DISCUSSION: This
      new surgical procedure (sleeve gastrectomy with loop bipartition: SG+LB) was
      evolved and derived from the combined concepts of sleeve gastrectomy with transit
      bipartition (SG+TB), single anastomosis duodenal-ileostomy (SADI), mini-gastric
      bypass (MGB) and duodenal-jejunal bypass (DJB) with less nutritional and surgical
      complications. CONCLUSION: Sleeve gastrectomy with loop bipartition may be a very
      effective and simple operation to treat uncontrolled DM associated with obesity
      with a lot of apparent advantages over most current metabolic procedures
      available at the moment.

PMID- 24441435
TI  - A rare cavernous hemangioma of the adrenal gland.
AB  - INTRODUCTION: Cavernous hemangiomas of the adrenal gland are rare. We report a
      case of a cavernous hemangioma of the adrenal gland presenting as an adrenal
      incidentaloma suspicious for adrenal cortical carcinoma (ACC). PRESENTATION OF
      CASE: A 78 year old woman was admitted after a fall. Abdominal computed
      tomography revealed a large right adrenal lesion with features suspicious for
      adrenal cortical carcinoma (5.4cm*3.3cm, unilateral, tumor calcifications,
      average Hounsfield units 55). The tumor was removed intact by a laparoscopic
      approach and pathology revealed a cavernous hemangioma of the adrenal gland.
      DISCUSSION: Adrenal incidentalomas are found in up to 10% of patients undergoing
      abdominal imaging. Differential diagnosis includes both benign and malignant
      lesions. Guidelines for removal of adrenal incidentalomas recommend surgery based
      on functional status, size, and presence of concerning features on diagnostic
      imaging. Cavernous hemangiomas are rare, benign vascular malformations which can
      be challenging to distinguish pre-operatively from malignant lesions such as ACC.
      CONCLUSION: Cavernous hemangiomas of the adrenal gland are exceedingly rare.
      These benign tumors have imaging features which may be suggestive of adrenal
      cortical carcinoma. The treatment of choice is surgical excision due the
      difficulty of excluding malignancy.

PMID- 24441437
TI  - Endovascular reconstruction of an interrupted inferior vena cava.
AB  - INTRODUCTION: Inferior vena cava (IVC) interruption was established as a
      procedure to treat refractory venous thromboembolism (VTE) complicated by
      pulmonary embolism. Ilio-caval thrombosis and lower limb chronic venous
      insufficiency (CVI) are well known long-term complications of IVC interruption,
      where subsequent treatments may carry significant morbidity and mortality.
      PRESENTATION OF CASE: We present here a case of chronic venous insufficiency
      resulting from IVC interruption with a vascular clip placed forty years
      previously. A novel approach utilising endovascular stents was used to
      reconstruct the iliocaval confluence and interrupted distal IVC without the need
      for laparotomy to remove the plicating clip. This procedure was associated with
      minimal morbidity and resulted with a quick resolution of the patient's CVI
      symptoms. DISCUSSION: Endovascular angioplasty and stenting is an alternative to
      open reconstruction of the interrupted inferior vena cava. We have demonstrated
      successful opening of a plication vascular clip using only endovascular
      utilities. Advantages include a shorter hospital stay, and reduced morbidity and
      mortality when compared to a re-do laparotomy. CONCLUSION: Endovascular stents
      may be used safely and effectively to reconstruct the surgically interrupted
      inferior vena cava in the treatment of chronic venous insufficiency.

PMID- 24441438
TI  - Hyperamylasaemia and ischaemic colitis.
AB  - INTRODUCTION: Ischaemic colitis is a differential diagnosis to be considered in
      patients who have a high cardiovascular risk. Presentation of severe ischaemia is
      usually that of an acute abdomen with passage of fresh blood per rectum, and
      hyperamylasaemia. PRESENTATION OF CASE: A 66-year-old gentleman was admitted to
      A&E with a short history of central abdominal pain, nausea, vomiting and fresh
      bleeding per rectum. A diagnosis of ischaemic colitis was made by the computed
      tomography (CT) scan findings of colonic thickening and pneumatosis, in addition
      to colonoscopy demonstrating sloughy mucosa and ulceration. Symptoms did not
      resolve with conservative management, therefore laparotomy+Hartmann's procedure
      was performed. Histology showed extensive areas of both partial and full
      thickness ischaemia with stricture. DISCUSSION: Amylase is an indicator of intra
      abdominal inflammatory processes. Hyperamylasaemia (normal <100U/l) is most
      frequently associated with pancreatitis; however, causation is not exclusive and
      other differentials including bowel ischaemia must be considered, although
      amylase is not a specific marker for ischaemic colitis. It is important to
      distinguish between ischaemic and ulcerative colitis. CONCLUSION: Intestinal
      ischaemia is a serious acute abdominal pathology that is associated with
      hyperamylasaemia, and frequently requires prompt surgical intervention to prevent
      subsequent mortality.

PMID- 24441439
TI  - Torsion of a huge accessory spleen in a 20-year-old patient.
AB  - INTRODUCTION: Accessory spleen is a rare condition. Torsion of accessory spleen
      can lead to acute abdomen. PRESENTATION OF CASE: We describe a young woman with
      an acute abdomen caused by torsion of accessory spleen. Abdominal computed
      tomography angiography (CTA) demonstrated an ischemic giant accessory spleen with
      a twisted vascular pedicle. An emergency laparotomy was performed with resection
      of the infarcted accessory spleen. DISCUSSION: Accessory spleen is a rare and
      asymptomatic condition. Torsion of accessory spleen is also uncommon. Abdominal
      pain is the main symptom. CTA is effective in reaching a diagnosis. Definitive
      treatment of an acute abdomen due to accessory splenic torsion is emergency
      accessory splenectomy. CONCLUSION: Elective accessory splenectomy should be
      recommended for known giant accessory spleen to prevent complications in future.

PMID- 24441440
TI  - Adrenal gunshot wound: Laparoscopic approach. Report of a case.
AB  - INTRODUCTION: Although there is no debate that patients with peritonitis or
      hemodynamic instability should undergo urgent laparotomy after penetrating
      abdominal injury, it is also clear that certain stable patients may be managed
      without operation. Controversy persists regarding use of laparoscopy.
      PRESENTATION OF CASE: We report a case of gunshot wounds with bullet in left
      adrenal gland and perirenal subcapsular hematoma. The patients had no signs of
      peritonitis but in the observation period we noted a significative blood loss, so
      we performed an exploratory laparoscopy. DISCUSSION: We found the bullet in
      adrenal parenchyma. The postoperative period was regular and the patient was
      discharged without any local or general complication. CONCLUSION: Although the
      data are still controversial, the importance of the laparoscopic approach is
      rapidly increasing also in case of penetrating trauma of the abdomen. This
      technique assumes both a diagnostic and therapeutic role by reducing the number
      of negative laparotomies.

PMID- 24441441
TI  - Gallbladder perforation: A rare complication of enteric fever.
AB  - INTRODUCTION: Gallbladder perforation is a rare complication of acute calculous
      cholecystitis in adults. Perforation of gallbladder due to enteric fever is
      extremely rare condition. Pre-operative diagnosis is rarely made and mortality is
      high. PRESENTATION OF CASE: We report a case of acalculous gallbladder
      perforation following enteric fever in a 14-year-old boy, who presented as acute
      abdomen and responded very well after emergency laparotomy and cholecystectomy.
      DISCUSSION: Enteric fever is common in tropics and a common cause of bowel
      perforation. Acute cholecystitis is a rare complication of typhoid and
      gallbladder perforation is extremely rare complication. Ultrasound and CT lack
      specificity to detect gallbladder perforation. Diagnosis is usually made intra
      operatively. Cholecystectomy is treatment of choice in such cases and provides
      good result. CONCLUSION: Gallbladder perforation secondary to enteric fever
      requires a high degree of clinical suspicion. In typhoid endemic region, it
      should be considered as a differential diagnosis in patient presenting with a
      history of prolonged fever and signs of peritonitis. Early diagnosis and
      immediate surgical intervention are very important in reducing the morbidity and
      mortality. Cholecystectomy is the choice with a good outcome.

PMID- 24441442
TI  - An unusual presentation of perforated appendicitis in epigastric region.
AB  - INTRODUCTION: Atypical presentations of appendix have been reported including
      backache, left lower quadrant pain and groin pain from a strangulated femoral
      hernia containing the appendix. We report a case presenting an epigastric pain
      that was diagnosed after computed tomography as a perforated appendicitis on
      intestinal malrotation. PRESENTATION OF CASE: A 27-year-old man was admitted with
      a three-day history of epigastric pain. Physical examination revealed tenderness
      and defense on palpation of epigastric region. There was a left subcostal
      incision with the history of diaphragmatic hernia repair when the patient was 3
      days old. He had an intestinal malrotation with the cecum fixed at the epigastric
      region and the inflamed appendix extending beside the left lobe of liver.
      DISCUSSION: While appendicitis is the most common abdominal disease requiring
      surgical intervention seen in the emergency room setting, intestinal malrotation
      is relatively uncommon. When patients with asymptomatic undiagnosed
      gastrointestinal malrotation clinically present with abdominal pain, accurate
      diagnosis and definitive therapy may be delayed, possibly increasing the risk of
      morbidity and mortality. CONCLUSION: Atypical presentations of acute appendicitis
      should be kept in mind in patients with abdominal pain in emergency room
      especially in patients with previous childhood operation for diaphragmatic
      hernia.

PMID- 24441443
TI  - Squamous cell carcinoma of middle rectum: Literature review.
AB  - INTRODUCTION: Squamous cell carcinoma SCC of the rectum is a distinct entity. We
      report a very rare case of squamous cell carcinoma of the middle rectum.
      PRESENTATION OF CASE: The patient was a 62-year-old woman who presented with a
      history of rectal bleeding and discomfort. Colonoscopy revealed a polypoid tumour
      of the middle rectum. Biopsies of this mass revealed a poorly differentiated SCC
      of the rectum. CT scan of the chest, abdomen and pelvis was negative for distal
      metastases. The patient received combined chemo-radiation followed by surgical
      excision. The postoperative period was uncomplicated. DISCUSSION: The
      pathogenesis of rectal SCC remains unclear and diagnosis is often delayed.
      Diagnostic criteria have been proposed. MRI of the rectum and trans-rectal
      endoscopic ultrasound R-EUS provide essential information to plan a therapeutic
      approach. The squamous cell carcinoma antigen level is not suitable for initial
      diagnosis of rectal SCC. Most authors conclude that the surgery is the gold
      standard treatment. Tumour stage is the most important prognostic predictor of
      SCC. CONCLUSION: Squamous cell carcinoma of the rectum is a distinct entity.
      Before the final choice of treatment is made, digestive surgeons should bear in
      mind this rare tumour.

PMID- 24441445
TI  - Emergent reversal of oral anticoagulation: review of current treatment
      strategies.

PMID- 24441444
TI  - Multiscale deconstruction of molecular architecture in corn stover.
AB  - Lignocellulosic composite in corn stover is a candidate biofuel feedstock of
      substantial abundance and sustainability. Its utilization is hampered by
      resistance of constituent cellulose fibrils to deconstruction. Here we use multi
      scale studies of pretreated corn stover to elucidate the molecular mechanism of
      deconstruction and investigate the basis of recalcitrance. Dilute acid
      pretreatment has modest impact on fibrillar bundles at 0.1 micron length scales
      while leading to significant disorientation of individual fibrils. It
      disintegrates many fibrils into monomeric cellulose chains or small side-by-side
      aggregates. Residual crystalline fibrils lose amorphous surface material, change
      twist and where still cross-linked, coil around one another. Yields from
      enzymatic digestion are largely due to hydrolysis of individual cellulose chains
      and fragments generated during pretreatments. Fibrils that remain intact after
      pretreatment display substantial resistance to enzymatic digestion. Optimization
      of yield will require strategies that maximize generation of fragments and
      minimize preservation of intact cellulosic fibrils. 

PMID- 24441447
TI  - Technology and the digitization of health care.

PMID- 24441448
TI  - The effect of alarm fatigue on the work environment.

PMID- 24441449
TI  - Ventricular fibrillation following synchronized cardioversion in junctional
      ectopic tachycardia: a pediatric case report.

PMID- 24441450
TI  - Ketorolac as an analgesic agent for infants and children after cardiac surgery:
      safety profile and appropriate patient selection.
AB  - Ketorolac has been used safely as an analgesic agent for children following
      cardiac surgery in selected populations. Controversy exists among institutions
      about the risks involved with this medication in this patient group. This article
      reviews the current literature regarding the safety of ketorolac for
      postoperative pain management in children after cardiac surgery. Specifically,
      concerns about renal dysfunction and increased bleeding risk are addressed.
      Additionally, the article details pharmacokinetics and potential benefits of
      ketorolac, such as its opioid-sparing effect. The literature reflects that the
      use of this medication is not well studied in certain pediatric cardiac patients
      such as neonates and those with single-ventricle physiology, and the safety of
      this medication in regards to these special populations is reviewed. In
      conclusion, ketorolac can be used in specific pediatric patients after cardiac
      surgery with minimal risk of bleeding or renal dysfunction with appropriate
      dosing and duration of use. 

PMID- 24441452
TI  - Achieving quality health outcomes through the implementation of a spontaneous
      awakening and spontaneous breathing trial protocol.
AB  - BACKGROUND: Continuous sedation infusions can lead to prolonged treatment with
      mechanical ventilation (MV), resulting in serious complications. Spontaneous
      awakening trials (SATs) and spontaneous breathing trials (SBTs) are strategies
      that limit the amount of sedative agents a patient receives and promote
      extubation. OBJECTIVE: The objective of this performance improvement project was
      to evaluate the outcomes of an evidence-based practice protocol that included
      SATs and SBTs on the duration of treatment with MV, ventilator utilization ratio
      (VUR), intensive care unit (ICU) length of stay (LOS), and incidence of self
      extubations and reintubations. METHODS: A convenience sample of 112 discharged
      patients' medical records was used for this descriptive, comparative secondary
      data analysis. An evidence-based SAT/SBT practice protocol was designed by a
      multidisciplinary team and implemented. Three months after the implementation, a
      retrospective medical record review was conducted to evaluate patient outcomes.
      RESULTS: The median duration of treatment with MV was significantly lower in the
      postprotocol group (3.8 days vs 2.7 days, U = 1222, Z = -2.013, P = .04, r =
      0.19). A significant decrease was found in the VUR (0.68 vs 0.52, U = 2.5, Z = 
      2.293, P = .02, r = 0.69). No difference was found in the ICU LOS and frequency
      of self-extubation or reintubation after a self-extubation between the
      preprotocol and postprotocol groups. Ten of 45 SAT opportunities (22%) and 67 of
      130 SBT opportunities (52%) were missed by the nurse or the respiratory
      therapist. CONCLUSION: The duration of treatment with MV and the VUR were reduced
      in patients who received the SAT/SBT protocol. The incidence of self-extubation
      was not different when an SAT was implemented. The ICU LOS was not reduced in
      patients who received SATs and SBTs.

PMID- 24441453
TI  - Evaluation of nurse engagement in evidence-based practice.
AB  - The purpose of this project was to explore nurses' willingness to question and
      change practice. Nurses were invited to report practice improvement
      opportunities, and participants were supported through the process of a practice
      change. The project leader engaged to the extent desired by the participant.
      Meetings proceeded until the participant no longer wished to continue, progress
      was blocked, or practice was changed. Evaluation of the evidence-based practice
      change process occurred. Fifteen nurses reported 23 practice improvement
      opportunities. The majority (12 of 15) preferred to have the project leader
      review the evidence. Fourteen projects changed practice; 4 were presented at
      conferences. Multiple barriers were identified throughout the process and
      included loss of momentum, the proposed change involved other disciplines, and
      low level or controversial evidence. Practice issues were linked to quality
      metrics, cost of care, patient satisfaction, regulatory compliance, and patient
      safety. Active engagement by nurse leaders was needed for a practice change to
      occur. Participants identified important problems previously unknown to hospital
      administrators. The majority of nurses preferred involvement in practice change
      based on clinical problem solving when supported by others to provide literature
      review and manage the process through committees. Recommendations include
      supporting a culture that encourages employees to report practice improvement
      opportunities and provide resources to assist in navigating the identified
      practice change. 

PMID- 24441454
TI  - Medication errors in the intensive care unit: ethical considerations.

PMID- 24441455
TI  - Interpretation of the low-voltage ECG.

PMID- 24441456
TI  - Cholesterol-based cationic lipids for gene delivery: contribution of molecular
      structure factors to physico-chemical and biological properties.
AB  - In this work, we prepared a series of cholesterol-based cationic (Cho-cat) lipids
      bearing cholesterol hydrophobe, natural amino acid headgroups (lysine/histidine)
      and linkage (carbonate ester/ether) bonds. In which, the natural amino acid
      headgroups made dominant contribution to their physico-chemical and biological
      properties. Among the lipids, the l-lysine headgroup bearing lipids (Cho-es/et
      Lys) showed higher pDNA binding affinity and were able to form larger sized and
      higher surface charged lipoplexes than that of l-histidine headgroup bearing
      lipids (Cho-es/et-His), they also demonstrated higher transfection efficacy and
      higher membrane disruption capacities than that of their l-histidine headgroup
      bearing counterparts. However, compared to the contributions of the headgroups,
      the (carbonate ester/ether) linkage bonds showed much less affects. Besides, it
      could be noted that, Cho-es/et-Lys lipids exhibited very high luciferase gene
      transfection efficiency that almost reached the transfection level of "gold
      standard" bPEI-25k, made them potential transfection reagents for practical
      application. Moreover, the results facilitated the understanding for the
      structure-activity relationship of the cholesterol-based cationic lipids, and
      also paved a simple and efficient way for achieving high transfection efficiency
      by modification of suitable headgroups on lipid gene carriers. 

PMID- 24441457
TI  - A synergistic combination therapy with paclitaxel and doxorubicin loaded micellar
      nanoparticles.
AB  - Doxorubicin was chemically conjugated to a biodegradable polymeric carrier as a
      polymer-doxorubicin (polymer-Dox) conjugate via an acid labile Schiff-base bond.
      Then, paclitaxel was physically encapsulated by the polymer-Dox conjugate to self
      assemble in water as micellar nanoparticles with both doxorubicin and paclitaxel
      in one nanoparticle. In this way, doxorubicin and paclitaxel were combined. The
      preparation of the polymer-doxorubicin conjugates, encapsulation of paclitaxel,
      characterization of nanoparticles was systematically studied and the biological
      evaluation of the free drug combination as well as the micellar platform
      combination in vitro was thoroughly detailed. 

PMID- 24441458
TI  - [The provocative normality--old and new--of the qualitative research].

PMID- 24441459
TI  - [Why to have a dossier on qualitative research].
AB  - Why a dossier on qualitative research. The main reasons for a dossier on
      qualitative research are presented, together with strengths and weaknesses of
      qualitative research compared to quantitative. The different perspectives offered
      by the two methods on the exploration and interpretation of phenomena are briefly
      described.

PMID- 24441460
TI  - [Reflections on qualitative research. Interview of Luisa Saiani with Luigina
      Mortari].
AB  - Reflections on qualitative research. Interview of Luisa Saiani to Luigina
      Mortari. Luigina Mortari, an internationally known expert of epistemology and
      qualitative research, was interviewed to explore her thoughts on issues relevant
      for qualitative research: when a research question can be considered relevant;
      key methodological elements; ethical issues.

PMID- 24441461
TI  - [Introduction to qualitative research: the main approaches and designs].
AB  - Introduction to qualitative research: the main approaches and designs. The main
      methods (phenomenology, ethnography, Grounded, narrative enquiry and case
      studies) and sampling technique of qualitative research are briefly outlined. A
      practical example is presented for each method.

PMID- 24441462
TI  - [Good and bad examples of qualitative research].
AB  - Good and bad examples of qualitative research. Not all the research papers are of
      good quality and contribute to the development of the knowledge. Good and less
      good examples of qualitative research are presented and commented on, exploring
      their contribution to the knowledge of a subject, and motivating why the research
      can be considered a good or less good example.

PMID- 24441463
TI  - [Qualitative research: an overlook of the literature].
AB  - Qualitative research: an overlook of the literature. Qualitative studies
      published in 2012-2013 were analysed. Over 4616 studies published (3 in Italian
      language), 295 use the grounded theory, 218 a phenomenological approach, 86
      ethnography, 14 narrative enquiry and 15 are case studies. A few studies and the
      methasmtheses were selected to present examples of areas of interest.

PMID- 24441464
TI  - [Resources for qualitative research: the DIPEx website].
AB  - Resources for qualitative research: the DIPEX website. DIPEx (Personal
      Experiences of Health & Illness) produces a website giving personal accounts of
      health and illness. These accounts are in written, audio and video format and aim
      to give information and support so that people are better informed about the life
      choices they might need to make when encountering a new health experience,
      serious illness or health problem. Modules on 75 illnessess/problems are
      available.

PMID- 24441465
TI  - [When patients talk about healing: a phenomenological qualitative study].
AB  - When patients talk about care: a qualitative phenomenological study.
      Introduction. Caring has been studied so far mainly from the nurses'point of
      view, but is equally important to elicit the patients' perspective to improve the
      understanding of actions and behaviors nurses can implement to respond to
      patients' expectations and idea of caring. Patients and nurses' perspectives may,
      in fact, be different. Aims. To describe and understand the caring experience of
      patients admitted to hospital, focusing on behaviors associated to a good caring.
      Methods. A qualitative, phenomenological hermeneutical research was conducted.
      Patients were interviewed with semi structured interviews and asked to tell when
      they had received a good care from nurses. Results. Ninety-three patients from
      different wards were interviewed. The caring dimensions described refer to the
      opportunity to experience a relationship of closeness with nurses, of being
      perceived as unique persons, understood, to relieve the sense of loneliness,
      sometimes experienced. Patients perceive that they are cared when receiving
      information consistent with their needs, that they are able to understand, when
      nurses are attentive and make them feel safe through constant monitoring and
      surveillance. Conclusions. The organizations should promote caring models
      oriented to the personalization of care, perceived as an essential element of
      care.

PMID- 24441466
TI  - [Lateral hostilities among emergency and critical care nurses. Survey in five
      hospitals of the Tuscany Region].
AB  - Lateral hostilities among emergency and critical care nurses. Survey in five
      hospitals of Tuscany Region. Introduction. Lateral hostilities (LHs) are a kind
      of workplace violence. They are defined as varieties of cruel, rude, antagonistic
      interactions between people at the same hierarchical level. Nurses are affected
      by LH from 5.7% to 65%, leading to reduced work motivation, psycho-physical
      disorders, and in some cases, drop out of the nursing profession. Objective. To
      quantify the LHs among nurses in the emergency departments (ED) and intensive
      care units (ICU) in 5 hospitals of Tuscany (Italy). To show the impact on the
      quality of their psycho-physical and professional lives. Method. Exploratory
      descriptive study, through closed-ended questionnaire. Results. 360/444 nurses
      (81%); 294 (81.6%) were victims of LHs during the past 12 months. Gossiping,
      complaints shared with others without discussing with the concerned person, and
      sarcastic comments were the most reported LHs. LHs occur more in EDs than ICUs
      (respectively 90% and 77%; p=0.0038). No statistically significant differences
      were observed for gender, age, or years of experience. The 17.7% of nurses asked
      to be moved from the ward, and 6.9% left it; 6.9% respondents had thought to
      leave the nursing profession; 235 (65.2%) experienced at least one LHs related
      disorder during the last year. Most reported symptoms were low morale, anxiety,
      and sleep disturbances. Conclusions. The incidence of LH and related disorders is
      high in EDs and ICUs, determining a low professional and psycho-physical quality
      of life.

PMID- 24441467
TI  - [Taste disorders in cancer patients].
AB  - Taste disorders in cancer patients. Introduction. Taste disorders are a relevant
      but often underestimated and under reported symptom in cancer patients. Taste
      disorders can be a consequence of the illness or its treatment, especially in
      head and neck cancer patients. Aims. To describe the physiologic mechanisms of
      taste disorders in cancer patients, their assessment and possible strategies for
      prevention and treatment. Methods. Literature review. Results. Taste disorders
      affect quality of life and may be responsible of the occurrence of food aversions
      with possible weight loss and malnutrition, associated to worst outcomes for
      toxicity and survival. In spite of the progresses in the last decade, the
      assessment of taste disorders is far from being satisfactory. In fact research
      focused on gastrointestinal consequences of illness and treatments, reserving
      only a marginal attention to taste disorders, in spite of their prevalence. The
      available knowledge of the mechanisms underlying the development of taste
      disorders in cancer patients are presented, together with assessment and
      treatment and prevention strategies. Discussion. Taste disorders are
      underreported and underestimated, in spite of their prevalence, especially in
      cancer patients, possibly for the wrong assumption that they cannot be treated.
      This may explain why they are often not reported by patients.

PMID- 24441468
TI  - [Guidelines for psychosocial care of cancer patients].
AB  - Guidelines for psychosocial care of cancer patients. The Italian Association of
      Medical Oncologists published in 2013 the update of the first edition of the
      Psychosocial Guidelines for the care of cancer patients. The guidelines, produced
      by a multidisciplinary group (medical doctors, nurses, oncologists, psychologists
      and patients) aim at recognizing the importance of psychosocial care in helping
      the patients and their relatives to overcome the effects of the diagnosis and the
      treatments on mental health and emotional wellbeing. In some cases the evidences
      available are not as hard as those supporting drug treatments: many outcomes such
      as the effectiveness of educational interventions, the patients' wellbeing,
      thrust, perception of support, for their nature and complexity require both
      quantitative and qualitative measurements. Lack of robust evidences such as those
      obtained from clinical trials, does not necessarily correspond to lack of
      effectiveness of the intervention nor should make us forget that patients' rights
      (to good care, information and support) should be guaranteed.

PMID- 24441469
TI  - Oxovanadium(V)-induced diastereoselective oxidative homocoupling of boron
      enolates.
AB  - Oxovanadium(v)-induced dl-selective oxidative coupling of (Z)-boron enolate was
      demonstrated to give the corresponding 2,3-disubstituted 1,4-diketone in a good
      yield. High selectivity (up to 94 : 6) was attained when the reaction was
      performed with VO(OPr-i)2Cl at -30  degrees C. 

PMID- 24441470
TI  - Discovery of directional and nondirectional pioneer transcription factors by
      modeling DNase profile magnitude and shape.
AB  - We describe protein interaction quantitation (PIQ), a computational method for
      modeling the magnitude and shape of genome-wide DNase I hypersensitivity profiles
      to identify transcription factor (TF) binding sites. Through the use of machine
      learning techniques, PIQ identified binding sites for >700 TFs from one DNase I
      hypersensitivity analysis followed by sequencing (DNase-seq) experiment with
      accuracy comparable to that of chromatin immunoprecipitation followed by
      sequencing (ChIP-seq). We applied PIQ to analyze DNase-seq data from mouse
      embryonic stem cells differentiating into prepancreatic and intestinal endoderm.
      We identified 120 and experimentally validated eight 'pioneer' TF families that
      dynamically open chromatin. Four pioneer TF families only opened chromatin in one
      direction from their motifs. Furthermore, we identified 'settler' TFs whose
      genomic binding is principally governed by proximity to open chromatin. Our
      results support a model of hierarchical TF binding in which directional and
      nondirectional pioneer activity shapes the chromatin landscape for population by
      settler TFs. 

PMID- 24441471
TI  - Single-molecule site-specific detection of protein phosphorylation with a
      nanopore.
AB  - We demonstrate single-molecule, site-specific detection of protein
      phosphorylation with protein nanopore technology. A model protein, thioredoxin,
      was phosphorylated at two adjacent sites. Analysis of the ionic current amplitude
      and noise, as the protein unfolds and moves through an alpha-hemolysin pore,
      enables the distinction between unphosphorylated, monophosphorylated and
      diphosphorylated variants. Our results provide a step toward nanopore proteomics.

PMID- 24441472
TI  - Computational resources for high-dimensional immune analysis from the Human
      Immunology Project Consortium.

PMID- 24441475
TI  - New dimensions in immunology.

PMID- 24441473
TI  - Beyond model antigens: high-dimensional methods for the analysis of antigen
      specific T cells.
AB  - Adaptive immune responses often begin with the formation of a molecular complex
      between a T-cell receptor (TCR) and a peptide antigen bound to a major
      histocompatibility complex (MHC) molecule. These complexes are highly variable,
      however, due to the polymorphism of MHC genes, the random, inexact recombination
      of TCR gene segments, and the vast array of possible self and pathogen peptide
      antigens. As a result, it has been very difficult to comprehensively study the
      TCR repertoire or identify and track more than a few antigen-specific T cells in
      mice or humans. For mouse studies, this had led to a reliance on model antigens
      and TCR transgenes. The study of limited human clinical samples, in contrast,
      requires techniques that can simultaneously survey TCR phenotype and function,
      and TCR reactivity to many T-cell epitopes. Thanks to recent advances in single
      cell and cytometry methodologies, as well as high-throughput sequencing of the
      TCR repertoire, we now have or will soon have the tools needed to comprehensively
      analyze T-cell responses in health and disease. 

PMID- 24441476
TI  - Optimization of the polarized Klein tunneling currents in a sub-lattice: pseudo
      spin filters and latticetronics in graphene ribbons.
AB  - We found that with an increase of the potential barrier applied to metallic
      graphene ribbons, the Klein tunneling current decreases until it is totally
      destroyed and the pseudo-spin polarization increases until it reaches its maximum
      value when the current is zero. This inverse relation disfavors the generation of
      polarized currents in a sub-lattice. In this work we discuss the pseudo-spin
      control (polarization and inversion) of the Klein tunneling currents, as well as
      the optimization of these polarized currents in a sub-lattice, using potential
      barriers in metallic graphene ribbons. Using density of states maps, conductance
      results, and pseudo-spin polarization information (all of them as a function of
      the energy V and width of the barrier L), we found (V, L) intervals in which the
      polarized currents in a given sub-lattice are maximized. We also built parallel
      and series configurations with these barriers in order to further optimize the
      polarized currents. A systematic study of these maps and barrier configurations
      shows that the parallel configurations are good candidates for optimization of
      the polarized tunneling currents through the sub-lattice. Furthermore, we discuss
      the possibility of using an electrostatic potential as (i) a pseudo-spin filter
      or (ii) a pseudo-spin inversion manipulator, i.e. a possible latticetronic of
      electronic currents through metallic graphene ribbons. The results of this work
      can be extended to graphene nanostructures.

PMID- 24441477
TI  - From the editor.

PMID- 24441478
TI  - The consumer-run business: people with psychiatric disabilities as entrepreneurs.
AB  - Consumer-run businesses create job opportunities for people with psychiatric
      disabilities through the production of goods and services for sale to the
      community. The success of the consumer-run business is determined by the extent
      to which it is economically viable, owned and operated by persons with
      psychiatric disabilities, enhances the well being of its individual members and
      strengthens the consumer community. This paper provides an overview of the
      consumer-run business as it has emerged in the area of mental health. It
      describes the limitations of traditional rehabilitation services approaches which
      have served as a catalyst for the development of these businesses. It outlines
      the key characteristics of the consumer-run business. Finally, the paper argues
      that the consumer-run business represents a fundamental shift away from
      vocational rehabilitation service models. 

PMID- 24441474
TI  - The promise and challenge of high-throughput sequencing of the antibody
      repertoire.
AB  - Efforts to determine the antibody repertoire encoded by B cells in the blood or
      lymphoid organs using high-throughput DNA sequencing technologies have been
      advancing at an extremely rapid pace and are transforming our understanding of
      humoral immune responses. Information gained from high-throughput DNA sequencing
      of immunoglobulin genes (Ig-seq) can be applied to detect B-cell malignancies
      with high sensitivity, to discover antibodies specific for antigens of interest,
      to guide vaccine development and to understand autoimmunity. Rapid progress in
      the development of experimental protocols and informatics analysis tools is
      helping to reduce sequencing artifacts, to achieve more precise quantification of
      clonal diversity and to extract the most pertinent biological information. That
      said, broader application of Ig-seq, especially in clinical settings, will
      require the development of a standardized experimental design framework that will
      enable the sharing and meta-analysis of sequencing data generated by different
      laboratories. 

PMID- 24441479
TI  - Development of an on-site, behavior-based safety audit for the residential
      construction industry.
AB  - The purpose of this study was to describe the development and implementation of
      an on-site, behavior-based safety audit based on a safety program designed
      specifically to reduce injuries and fatalities in the residential construction
      industry. The audit was used to assess safety hazards and safety compliance on
      residential construction work sites. Safety behaviors were scored as all-or-none.
      A high score was related to high safety compliance. A total of 195 audits were
      performed on residential construction companies from varying trades. Analysis of
      mean total scores indicated that companies that had received some form of safety
      training scored significantly higher than companies that had not received any
      (P<0.01). Analysis of mean total scores between company trades indicated that
      masonry/stucco application companies had significantly lower scores than most
      other trades represented (P<0.01). Challenges in designing, administering and
      analyzing the safety audits are discussed. 

PMID- 24441480
TI  - Evaluation of HomeSafe: an injury and illness prevention program in residential
      construction.
AB  - OBJECTIVES: To design a program evaluation to determine the effectiveness of a
      novel safety and health program in residential construction. STUDY DESIGN: The
      overall program evaluation incorporates five separate studies with designs
      including: pre-test-post-test control group designs for determining program
      effects on safety culture and safe work behaviors, and cohort designs to assess
      longitudinal changes in injury rates and workers compensation costs. RESULTS:
      Preliminary data from 252 respondents who completed a two-page questionnaire
      after attending an initial training session indicated that the innovative
      HomeSafe Program has been well received. Companies who have joined the program to
      date are not representative of the broader population of businesses in the
      residential construction industry, as they generally are larger with heightened
      concerns for health and safety. CONCLUSIONS: Evaluating a safety and health
      program being introduced into the dynamic residential construction industry
      presents numerous challenges which are discussed.

PMID- 24441481
TI  - A review of the design of educational programs for upper extremity work injury
      prevention.
AB  - In the absence of literature on upper extremity (UE) injury prevention programs,
      this study gathered data on educational programs currently available to enhance
      future programming. A telephone survey with written follow-up for verification
      and accuracy was used to collect descriptive data about the expected outcomes,
      educational content, program parameters and evaluation methods for UE injury
      prevention programs offered by nationally based companies. Six companies
      participated in the survey. Changes in employee behaviors and lifestyles were the
      most frequently expected outcomes. The educational content consistently contained
      information on anatomy and physiology and frequently contained risk factor
      information. Lectures were the primary form of presentation, with limited
      opportunity for practice or problem solving. Two-hour programs were typically
      offered on site for groups of 20-25 participants at charges ranging from $100 to
      $300 per hour. The inconsistencies in current programming and insufficient
      definition of efficacy measures provide little guidance on how UE prevention
      programs should be designed. 

PMID- 24441482
TI  - Determining the effectiveness of thresholds, an intervention to enhance the
      career development of young people with physical disabilities.
AB  - People with disabilities have lower work force participation rates than the
      general public. One factor that has been attributed to this is a lack of
      vocational programs for adolescents with disabilities. Thresholds is a vocational
      program designed to enhance the career development strategies of adolescents with
      physical disabilities. In a three-part series, participants reflect on who they
      are, clarify their career future and explore the world of work, and test out
      strategies for investigating career opportunities and addressing obstacles to
      career success. Following pilot testing, Thresholds was field tested with two
      groups of adolescents in two urban centres in Canada. Findings suggested that
      this program could enhance the vocational decision-making abilities and self
      appraisal skills of participants. Entry level characteristics of participants
      were critical in determining the extent of change. Feedback encouraged
      modifications to make the program more useful and effective. 

PMID- 24441483
TI  - The physical and psychosocial environments in Swedish schools: quality aspects
      and relations to pupil-injury determinants as perceived by school principals.
AB  - The study investigated relations between the quality of the physical and
      psychosocial environments in Swedish schools and pupil-injury determinants as
      perceived by school principals. Data came from a representative sample of public
      sector Swedish schools. Schools were divided into four classes on the basis of
      the types and magnitudes of environmental problems they experienced. Associations
      between problems and type of school, type of district, and degree of importance
      attributed to various pupil-injury determinants were measured. Two schools in
      three were classified as having no environmental problems, and one in 20 as
      having both types. Significant associations were found between type of problem
      (environmental load), type of district and perceptions of some injury-inducing
      factors. Improvements to the school environment may benefit pupils' education and
      development as well as their safety and well-being. The study provides an aid for
      the setting of priorities in these respects. 

PMID- 24441484
TI  - Part I: the effect of long-term exposure to organic solvents on memory: a cross
      sectional study.
AB  - This study focuses on a wide range of different aspects of memory functions
      trying to ascertain a possible profile of memory changes, which take place
      following long-term exposure to organic solvents. The research design was cross
      sectional. Study population included 31 industrial painters who were exposed at
      work to organic solvents and 31 unexposed workers. Workers after long-term
      exposure to organic solvents showed significant decline in memory as indicated in
      all three standard memory tests (i.e. Wechsler Memory Scale - Revised, Benton
      Revised Visual Retention Test, and Rey Auditory Verbal Learning Test). The
      results of Rey Auditory Verbal Learning Test showed a negative correlation with
      exposure index indicating that the more intensive and longer the time of exposure
      was, the more impaired is the verbal memory. It was also found that the affect of
      age on memory was stronger among workers after long-term exposure to organic
      solvents compared to the unexposed workers. 

PMID- 24441485
TI  - The Feldenkrais Method(r) in rehabilitation: a review.
AB  - Musculoskeletal disorders are often suggested to be caused, in part, by poor
      postural behaviors that are associated with occupational demands. The inefficacy
      of conventional strategies to elicit postural correction has prompted many to
      seek alternative techniques such as the Feldenkrais Method(r). The rapidly
      growing use of the Feldenkrais Method(r) by laypersons and professionals has been
      fueled by extravagant claims and data published in non-peer-reviewed sources, for
      the effectiveness of this technique has been poorly documented in peer-reviewed
      publications. Therefore the purpose of this review was to critically assess the
      literature on the Feldenkrais Method(r) in both juried and non-juried sources.
      The results have generally indicated some improvement with Feldenkrais(r)
      interventions, however, these improvements are not nearly as large as suggested
      by the anecdotal claims. Unfortunately, most of the juried and non-juried
      findings and conclusions are questionable due to inadequately controlled studies
      and other serious methodological problems. As such, determination of the
      effectiveness of the Feldenkrais Method(r) based on the literature is difficult
      at best, and the only justifiable conclusion is that more study is warranted. 

PMID- 24441486
TI  - The relationship between job search skills and employability for persons with
      mild mental retardation.
AB  - Persons with mental retardation who possess applicable adaptive skills are
      usually able to obtain jobs in labor markets. However, some persons who show high
      scores with social and prevocational skills are unable to obtain jobs and the
      reasons for their unemployability are unknown. Twelve subjects with mild
      retardation who failed to obtain jobs were evaluated for their social and
      prevocational skills at the Tokyo Metropolitan Rehabilitation Center for the
      Physically and Mentally Handicapped. The evaluation was performed using the
      Social and Prevocational Information Battery-Revised which was developed by
      Halpen and Irvin. The results showed 12 subjects presented lower scores either in
      the Job Search Skills area or in other areas in spite of their high scores on the
      Total Battery. Moreover, these subjects also showed behavior problems. The study
      suggests that those with high scores on the Total Battery, but low scores in Job
      Search Skills, show a tendency to fail to obtain a job in competitive job
      placement. It seems that these persons have adjustment problems and need special
      support services to secure their employability. 

PMID- 24441487
TI  - Fibromyalgia: symptoms, treatment and strategies for daily life and work.

PMID- 24441488
TI  - The global effects of the tobacco industry.
AB  - The politics, economics, health impacts, and regulation of the tobacco industry
      are common themes in recent debates. This paper documents worldwide impacts of
      tobacco use, including the health implications as well as the politics and
      economics of tobacco regulation. A review of the proposed settlement and
      potential legislation is presented. Methods of occupational therapy intervention
      are also discussed. 

PMID- 24441491
TI  - From the editor.

PMID- 24441489
TI  - Impact of the Dayton Tire case.
AB  - Three of the more pertinent legal cases in the United States concerning the
      performance of ergonomists are summarized. The results of the cited cases have
      impact on the validity of the NIOSH lifting formulae, the lack of scientific
      evidence relating performance of jobs with alleged ergonomic stressors with
      specific medical pathology, and the gold standard for expert witness testimony.
      The cases, taken together, should act as a catalyst for ergonomists to improve
      their level of scientific justification for their work and conclusions. 

PMID- 24441492
TI  - Anterior chest support, muscular activity and subjective rating of exertion
      during microtome sectioning.
AB  - Seven females, six laboratory assistants, participated in the experimental part
      of the study. The level of muscular activity in different sitting work postures
      was recorded, using surface electrodes, as full-wave-rectified and low-pass
      filtered EMG, and normalised. The laboratory assistants also rated the degree of
      exertion in four different body regions during their ordinary microtome
      sectioning work, comparing the use of anterior chest support with the use of
      their usual chair with lumbar support. The use of anterior chest support reduced
      the muscular activity in the lumbar back muscles but increased it in the shoulder
      muscles. Perceived exertion in the neck, shoulders and thoracic back regions
      increased. Anterior chest support does not seem to solve the problem of neck- and
      shoulder load-elicited pain during the work of preparing laboratory sections. 

PMID- 24441493
TI  - The effect of typing frequency and speed on the incidence of upper extremity
      cumulative trauma disorder.
AB  - Typing in the work setting, with its emphasis on speed, force and repetitive
      movements and its tendency to be performed under less than optimum conditions has
      been one of the major causes of upper extremity cumulative trauma disorder (CTD).
      This disorder, also known as overuse syndrome, is a chronic condition believed to
      result from habitual overuse of the digits, hands or arms. The objective of this
      study was to examine the relationship between typing habits, specifically the
      influence of typing frequency, speed and style, on the incidence of injury. One
      hundred Israeli female typists aged between 20 and 60 years with no prior history
      of orthopedic or neurological disease participated in the study. Data collection
      took place at the work setting and consisted of a clinical evaluation of the
      upper extremities and trunk, a typing test, and a questionnaire which included
      questions concerning demographic information, occupational history, and upper
      extremity usage in the home and at work. Subjects were asked whether they had
      suffered from pain or other symptoms in the upper extremity (shoulder, arm,
      forearm, elbow or hand) on more than three occasions in the last year or on one
      occasion lasting more than a week. Subjects who answered no to this question were
      designated as 'non-sufferers'. Those who answered yes to the question were
      designated 'sufferers'. The 100 women who participated in the study represented a
      wide range of ages and educational levels. The variables describing on-the-job
      performance showed a wide range of values. Similar variability was found in the
      anthropometric variables. On the basis of the subjective criterion, 40 of the
      women belonged to the group labeled 'sufferers'. The remaining 60 subjects
      belonged to the group of 'non-sufferers'. The Odd's ratio test (OR), a common
      statistical procedure for risk factor estimation, was used to determine threshold
      levels associated with the development of CTD. Age, hours worked per week, typing
      speed, and years worked as a typist were variables in which at least one cut-off
      value generated a significant OR. The delineation of factors associated with
      typists who are classified as 'sufferers' establishes a portrait of the typical
      worker at risk for the development of CTD and provides insight into ways in which
      employers, clinicians and workers themselves could reduce the risk of CTD. 

PMID- 24441494
TI  - Age and occupational accidents in the light of fluctuations on the labor market:
      the case of Swedish non-ferrous ore miners.
AB  - This study examines non-specific and specific age-related accident frequencies
      among Swedish non-ferrous are miners. Age-related accident ratios (ARs) were
      calculated for all accidents aggregated and for different accident types over a
      ten-year period, using five age categories and three time intervals. ARs tended
      to be lower among older workers but they varied between age groups and time
      periods for almost all accident types. They were higher at the end than at the
      start ofthe study period for the age cohort 25-34 for all accident types, and for
      the cohort 16-24 for two accident types. The results suggest that age-related
      risks are influenced by labor-market factors. In physically demanding jobs,
      reductions in personnel may expose middle-age and younger workers to higher
      risks, because of 'basic capacities' being exceeded or due to a lack of relevant
      experience. 

PMID- 24441495
TI  - Prediction of functional capacities.
AB  - OBJECTIVE: This study explores the hypothesis that clients with low back injury
      can estimate their own functional capacities for waist-level lifting, lifting
      from the floor, and standing tolerance prior to formal functional capacity
      testing. SUMMARY OF BACKGROUND DATA: The frequent use of functional capacity
      evaluations for clients with industrial injuries and health care cost containment
      prompted research on the appropriateness and need for ohjective functional
      capacity evaluations. STUDY DESIGN/METHODS: All clients referred to the Sister
      Kenny Institute Work Injury Program for functional capacity evaluations from July
      1991 to May 1992 were screened for eligibility and willingness to participate.
      Seventy-five subjects participated in the study. These subjects predicted their
      capacities prior to formal functional capacities testing; formal testing results
      were then compared to the predictions. RESULTS: RESULTS indicated the majority of
      low back injured clients' actual test scores were not within 20 tests.
      CONCLUSION: The outcome of this study indicates it is difficult for clients to
      accurately predict their own functional capacities following low back injuries.
      Therefore, when functional capacities remain in question, functional capacity
      evaluations continue to be a valuable and cost-effective route to promote a safe
      return to work.

PMID- 24441496
TI  - Time use, time management and academic achievement among occupational therapy
      students.
AB  - The purpose of this study was to examine time use patterns and variables related
      to time use, including feelings about time use, time management, and academic
      achievement, among normal college students. Time use was examined from the
      perspective of the model of human occupation. One hundred and six male and female
      occupational therapy students enrolled at Worcester State College in Worcester,
      MA completed two self-report questionnaires and a demographic questionnaire. The
      subjects completed the Occupational Questionnaire (Riopel Smith, Kielhofner, and
      Watts, 1986) which measured time use (activities engaged in during a typical 24-h
      period), and feelings about time use (related to competence, value, enjoyment)
      for the activities they reported. In addition, they completed the Time Management
      Questionnaire (Britton and Tesser, 1990, which measured their time attitudes,
      preferences for short range planning, and preferences for long range planning.
      The results of the study suggest that older students and those experiencing role
      overload perceive themselves as less competent, and value and enjoy their time
      use less than younger students and those with fewer role demands. In addition,
      the use of time management was related to academic achievement. Implications of
      the findings are discussed. 

PMID- 24441497
TI  - The effects of vibration on workers.
AB  - Therapists working in the area of work rehabilitation have seen the incidence of
      cumulative trauma disorders from vibration increase dramatically over the past
      decade. Vibration affects millions of workers each year. The effects of vibration
      can be seen in either a segmental or whole-body fashion. The purpose of this
      article is to review the literature that examines whole-body vibration, hand-arm
      vibration syndrome, and suggestions for preventative strategies are presented.
      This article concludes with a case study in order to assist the reader in
      synthesizing the relevant information provided. 

PMID- 24441498
TI  - The 3D Static Strength ProgramTM.

PMID- 24441500
TI  - Contents of journals relating to work.

PMID- 24441499
TI  - Competency in ergonomics for rehabilitation professionals, November 1995.

PMID- 24441501
TI  - Total mercury, organic mercury and mercury fractionation in soil profiles from
      the Almaden mercury mine area.
AB  - Soil profiles located in the mining district of Almaden were investigated for
      total Hg, organic Hg fraction and Hg distribution by selective sequential
      extraction. A four-step sequential extraction method (labile Hg species, humic
      and fulvic complexes, elemental Hg and bound to crystalline oxides and Hg sulfide
      and refractory species) was performed. Total Hg concentrations ranged from 13 to
      64 mg per kg dry mass. A clear relationship between the depth and Hg content was
      found since Hg concentration decreases downwards, which is indicative of
      anthropogenic contamination via deposition processes from nearby mine waste.
      Significant organic Hg concentrations were found in all the tested soil profiles
      ranging from 79 to 287 MUg kg(-1) (dry weight). It seems that organic Hg was
      strongly influenced by elemental Hg (r = 0.79) and to a lesser extent by the
      organic carbon content (r = 0.57). The fractionation revealed that Hg exists
      mainly as cinnabar in the studied soils, which is one of the least available and
      mobile Hg species, and as elemental Hg as well. The most mobile Hg fractions only
      accounted for 3.2 to 7.7% of the total Hg content, with the main contribution
      being the humic and fulvic complexes fraction. The elemental Hg fraction
      increased with depth indicating a migration to deeper soil layers. In contrast,
      the surface layers showed an enrichment in the fraction bound to sulfide, which
      means that Hg is mostly deposited as cinnabar particles from non-processed ore in
      this area. 

PMID- 24441502
TI  - Vaccination therapy for non-small-cell lung cancer.
AB  - PURPOSE OF REVIEW: Recent advances in our understanding of cancer immunology
      resulted in the development of promising therapeutic agents for either nonantigen
      specific immunotherapy, for example, monoclonal antibodies targeting immune
      checkpoints on the T-cell lymphocyte, and antigen-specific immunotherapy or
      vaccination. Here, we review the recently reported results from randomized
      controlled trials (RCTs) with the latter approach. RECENT FINDINGS: Several
      trials indicated feasibility, safety, and potential for better patient outcomes.
      In resected early stage non-small-cell lung cancer, a phase II RCT with the MAGE
      A3 vaccine showed a trend for improved disease-free interval (hazard ratio 0.75),
      now further evaluated in the large MAGRIT (MAGE-A3 as Adjuvant NSCLC
      Immunotherapy Trial) study. In stage III after chemoradiotherapy, the phase III
      START (Stimulating Targeted Antigenic Responses to NSCLC) trial with L-BLP25
      vaccine resulted in a remarkable 10-month improvement in median survival in the
      concurrent chemoradiotherapy subgroup. In the advanced setting, the phase III
      study with the allogeneic tumor cell vaccine belagenpumatucel-L did not improve
      survival in the whole study, but interesting effects were seen in subgroups.
      SUMMARY: Recent non-small-cell lung cancer vaccination trials did not meet their
      primary endpoint, but showed clear patient benefits in subgroup analyses.
      Confirmatory trials and identifying patients who will benefit using predictive
      factors, will hopefully bring these approaches in the clinic in the near future.

PMID- 24441504
TI  - New developments in the treatment of squamous cell lung cancer.
AB  - PURPOSE OF REVIEW: To highlight the recent developments in the molecular
      characterization of lung squamous cell carcinoma (SQCC) and to summarize the
      current clinical trials of targeted agents. RECENT FINDINGS: Lung SQCC is the
      second-largest histological subtype of nonsmall-cell lung cancer after lung
      adenocarcinoma and is closely associated with tobacco smoking. Targeted therapies
      have been successfully used for the treatment of lung adenocarcinoma but have not
      been implemented in the treatment of lung SQCC to date. Both lung adenocarcinomas
      and SQCCs are characterized by specific somatic DNA modifications such as exonic
      mutations, copy-number alterations, and genomic rearrangements which are
      substantially different between the two subtypes. Progress in genomic
      characterization using next-generation sequencing (NGS) technologies makes it
      possible to investigate these somatic DNA modifications at the whole-genome level
      and to generate comprehensive profiles of genetic alterations. Application of NGS
      in lung SQCC led to a more detailed understanding of the possible targets and
      will identify new targeted therapeutic approaches in the near future. SUMMARY: In
      this review, we highlight the current knowledge of molecular targets, clinical
      trials of targeted agents, and druggable aberrations in lung SQCCs.

PMID- 24441503
TI  - Systemic treatment of malignant pleural mesothelioma: new agents in clinical
      trials raise hope of relevant improvements.
AB  - PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a rare malignancy with
      limited therapeutic options and its incidence is still increasing in both Europe
      and the developing nations. Prognosis of MPM patients is poor even if the median
      survival durations have been slightly improved after the introduction of the up
      to-date chemotherapy combination with pemetrexed and cisplatin. There is a
      continuing unmet need to develop better systemic treatment for this disease, but
      the rarity of the tumor type creates formidable challenges in clinical trial
      research. RECENT FINDINGS: Better understanding of the molecular machinery of MPM
      leads to the design and synthesis of novel compounds targeted against pathways
      identified as crucial for MPM cell proliferation and metastasis. Most efforts aim
      at improving standard first-line therapy, or developing effective second-line
      treatments. Several classes of drugs are currently being explored either in
      combination with cisplatin and pemetrexed or as single agent for relapsed or
      progressive MPM. SUMMARY: This review focuses on several ongoing or recently
      completed clinical trials investigating novel, promising agents as first-line or
      second-line therapy for advanced MPM.

PMID- 24441505
TI  - Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma.
AB  - PURPOSE OF REVIEW: The use of agents which exhibit the ability to potently
      activate the innate immune response has gained significant interest as
      therapeutics to treat cancer. We will review the history and the current
      applications of these agents to treat skin cancer and cutaneous T-cell lymphoma.
      RECENT FINDINGS: Particular attention has been focused upon Toll-like receptor
      (TLR) agonists, including imidazoquinolines, which can trigger TLR 7 and TLR 8,
      and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides, which activate TLR 9
      expressing cells. Imiquimod, a TLR 7 agonist, has been found to be efficacious
      for basal cell and squamous cell cancers, as well as cutaneous T-cell lymphoma
      and lentigo maligna melanoma. CpGs have demonstrated efficacy for cutaneous T
      cell lymphoma. Additional more potent compounds, including resiquimod, are
      presently in clinical trials for several types of skin cancers. SUMMARY: TLR
      agonists that can activate the innate immune response have been used to treat a
      variety of skin cancers including basal cell cancer, squamous cell cancer,
      lentigo maligna melanoma and cutaneous T-cell lymphoma. Significant clinical
      efficacy has been observed for all of these conditions. It is anticipated that
      additional members of the TLR agonist family will be available in the clinic for
      the future treatment of skin cancers as well as other malignancies.

PMID- 24441506
TI  - Neural crest stem cells in melanoma development.
AB  - PURPOSE OF REVIEW: Metastatic melanoma is the most aggressive skin cancer and
      despite tremendous efforts and considerable progress in clinical treatment of
      melanoma patients within recent years, it remains a deadly disease. Current
      treatments affect melanoma cells indiscriminately, while accumulating evidence
      suggests that melanoma might be a disease of stem cells. This review aims to
      summarize the important accomplishments in the field and to emphasize the common
      molecular and cellular mechanisms regulating self-renewal of neural crest stem
      cells (NCSCs) and melanoma cells. RECENT FINDINGS: A growing number of
      publications highlight the existence of phenotypic and functional similarities
      between embryonic NCSCs and melanoma cells. These studies provide compelling
      evidence that the propagation of melanoma cells critically depends on genes
      instrumental in neural crest development. The example of Sox10 and Rac1 genes
      provides detailed illustration of how interfering with these important genes for
      neural crest development can prevent melanoma formation. SUMMARY: The development
      of new therapies, targeting RAF-MEK-ERK pathway, provided major improvements in
      outcomes for patients with metastatic melanoma; however, acquired resistance
      followed by tumor recurrence represents a major clinical challenge. The striking
      parallels between embryonic NCSCs (eNCSCs) and melanoma cells might lead to the
      development of new targeted therapeutics selectively eliminating cell populations
      accountable for tumor initiation, progression and relapse.

PMID- 24441507
TI  - Screening for lung cancer.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the
      current data about low-dose computed tomography (LD-CT) lung cancer screening.
      RECENT FINDINGS: The National Lung Screening Trial (NLST) was the first study
      that provided statistical evidence that LD-CT screening for lung cancer
      significantly reduces lung cancer mortality by 20%. Three statistically
      underpowered European trials could not confirm the positive effect of LD-CT
      screening on lung cancer mortality. Major obstacles in lung cancer screening are
      overdiagnosis and the large number of false-positive results. In the NLST, more
      than 24% of the screens were positive, most of which (96.4%) proved to be benign
      in nature. Optimized protocols for the workup of detected nodules may help to
      reduce the number of false-positive screens. SUMMARY: Currently, the NLST is the
      only sufficiently powered trial to report a lower mortality rate with LD-CT
      screening. Long-term follow-up data are still anticipated on the European
      screening trials. Furthermore, data on the extent of the potential dangers of LD
      CT screening, such as overdiagnosis, false-positive results, and the effect of
      cumulative radiation dose, have yet to be investigated thoroughly.

PMID- 24441508
TI  - Beyond radio-displacement techniques for identification of CB1 ligands: the first
      application of a fluorescence-quenching assay.
AB  - Cannabinoid type 1 Receptor (CB1) belongs to the GPCR family and it has been
      targeted, so far, for the discovery of drugs aimed at the treatment of
      neuropathic pain, nausea, vomit, and food intake disorders. Here, we present the
      development of the first fluorescent assay enabling the measurement of kinetic
      binding constants for CB1 orthosteric ligands. The assay is based on the use of
      T1117, a fluorescent analogue of AM251. We prove that T1117 binds endogenous and
      recombinant CB1 receptors with nanomolar affinity. Moreover, T1117 binding to CB1
      is sensitive to the allosteric ligand ORG27569 and thus it is applicable to the
      discovery of new allosteric drugs. The herein presented assay constitutes a
      sustainable valid alternative to the expensive and environmental impacting
      radiodisplacement techniques and paves the way for an easy, fast and cheap high
      throughput drug screening toward CB1 for identification of new orthosteric and
      allosteric modulators.

PMID- 24441509
TI  - Does participation in physical education reduce sedentary behaviour in school and
      throughout the day among normal-weight and overweight-to-obese Czech children
      aged 9-11 years?
AB  - Participation of 9 to 11-year-old children in physical education lessons (PEL)
      contributes to a significantly higher duration of moderate-to-vigorous physical
      activity (MVPA) during the school day and, in overweight/obese girls and normal
      weight boys, to an increase in overall daily MVPA as shown by previous research.
      However, it is not known whether this increase in MVPA is at the expense of light
      physical activity (LPA) or sedentary behaviour (SED). SED, LPA, and MVPA were
      assessed in 338 schoolchildren aged 9-11 years (50.3% girls; 29.6%
      overweight/obese) over two school days (with and without a PEL) using a triaxial
      accelerometer during various segments of the school day. SED, LPA, and MVPA were
      quantified based on the duration of the activity (minutes). Participation in PEL
      led to significantly higher school MVPA in the overweight/obese and normal-weight
      girls and boys (p < 0.005) compared to MVPA of those children on the school day
      without PEL. Participation in PEL led to a significantly higher overall daily
      MVPA duration compared to that during the day without PEL for the
      overweight/obese girls (p < 0.05), normal-weight girls (p < 0.05) and boys (p <
      0.005). Participation in PEL contributed not only to significantly higher LPA in
      the normal-weight girls and boys (p < 0.01) during the school day but also
      reduced school-time SED in the overweight/obese children (p < 0.01) and normal
      weight girls (p < 0.005). Moreover, participation in PEL significantly reduced
      the overall daily SED in the normal-weight children and overweight/obese boys (p
      < 0.05). Adding one PEL to the daily school routine appears to be a promising
      strategy for effectively reducing SED in children. 

PMID- 24441510
TI  - Biocontrol of Fusarium graminearum growth and deoxynivalenol production in wheat
      kernels with bacterial antagonists.
AB  - Fusarium graminearum is the main causal pathogen affecting small-grain cereals,
      and it produces deoxynivalenol, a kind of mycotoxin, which displays a wide range
      of toxic effects in human and animals. Bacterial strains isolated from peanut
      shells were investigated for their activities against F. graminearum by dual
      culture plate and tip-culture assays. Among them, twenty strains exhibited potent
      inhibition to the growth of F. graminearum, and the inhibition rates ranged from
      41.41% to 54.55% in dual-culture plate assay and 92.70% to 100% in tip-culture
      assay. Furthermore, eighteen strains reduced the production of deoxynivalenol by
      16.69% to 90.30% in the wheat kernels assay. Finally, the strains with the
      strongest inhibitory activity were identified by morphological, physiological,
      biochemical methods and also 16S rDNA and gyrA gene analysis as Bacillus
      amyloliquefaciens. The current study highlights the potential application of
      antagonistic microorganisms and their metabolites in the prevention of fungal
      growth and mycotoxin production in wheat kernels. As a biological strategy, it
      might avoid safety problems and nutrition loss which always caused by physical
      and chemical strategies. 

PMID- 24441511
TI  - An integrative review of the mental health of partners of veterans with combat
      related posttraumatic stress disorder.
AB  - The aim of this article is to present an integrative review of the mental health
      of veteran partners living with veterans with combat-related posttraumatic stress
      disorder (PTSD). Living with a veteran with PTSD affects the psychological well
      being and health outcomes of a veteran partner. Fourteen research articles that
      focused on the mental health of military partners, which directly influence the
      psychological well-being of veteran partners, were reviewed. Findings indicate
      that a range of mental health concerns exist among veteran partners living with
      veterans with PTSD. The mental well-being of veteran partners is affected by the
      emotional strain of living and caring for veterans with PTSD. For years, the
      partner's presence has been overlooked in the PTSD treatment. However, to promote
      the comprehensive health of veterans with PTSD, it is paramount to understand the
      mental health state of veteran partners. Understanding the mental health state of
      veteran partners will provide a broader perspective to the plight of veteran
      partners. 

PMID- 24441512
TI  - Lateral patellar luxation in dogs: a retrospective study of 65 dogs.
AB  - OBJECTIVE: To report the signalment and clinical features of dogs with non
      traumatic lateral patellar luxation and to report the complications and outcomes
      following surgery. METHODS: A multicentre retrospective study was performed.
      Medical records were reviewed and the signalment, clinical features, and
      treatment of dogs presenting with lateral patellar luxation were recorded. In
      dogs treated surgically, the outcome and complications were investigated.
      RESULTS: Sixty-five dogs (95 stifles) were included; 39 were male and median age
      at presentation was 10 months. Breeds were classified as small (n = 6), medium (n
      = 23), large (n = 27), and giant (n = 9). Lateral patellar luxation was
      classified as grade I (n = 14), II (n = 41), III (n = 29), and IV (n = 11).
      Conformational abnormalities were noted in 34 stifles; genu valgum was the most
      common (n = 28). Higher-grade luxation was associated with a younger age at
      presentation (p = 0.032) and genu valgum (p = 0.01). Surgery was performed on 58
      stifles, 22 of which sustained one or more complications; 16 complications were
      managed conservatively, four with implant removal and six with revision surgery.
      Surgeon-assessed outcome was good or excellent in 47 of the 51 dogs available for
      review. CONCLUSIONS: Non-traumatic lateral patellar luxation is a disease of
      predominantly medium and large breed dogs. It has several similar clinical
      features and can be surgically treated in a similar manner to medial patellar
      luxation with similar types of complications and outcomes expected.

PMID- 24441513
TI  - Implementation of The World Starts With Me, a comprehensive rights-based sex
      education programme in Uganda.
AB  - This article presents a process evaluation of the implementation of the sex
      education programme the World Starts With Me (WSWM) for secondary school students
      in Uganda. The purpose of this mixed-methods study was to examine factors
      associated with dose delivered (number of lessons implemented) and fidelity of
      implementation (implementation according to the manual), as well as to identify
      the main barriers and facilitators of implementation. Teachers' confidence in
      teaching WSWM was negatively associated with dose delivered. Confidence in
      educating and discussing sexuality issues in class was positively associated with
      fidelity of implementation, whereas the importance teachers attached to open sex
      education showed a negative association with fidelity. Main barriers for
      implementing WSWM were lack of time, unavailability of computers, lack of student
      manuals and lack of financial support and rewards. Other barriers for successful
      implementation were related to high turnover of staff and insufficient training
      and guidance of teachers. Teachers' beliefs/attitudes towards sexuality of
      adolescents, condom use and sex education were found to be important socio
      cognitive factors intervening with full fidelity of implementation. These
      findings can be used to improve the intervention implementation and to better
      plan for large-scale dissemination of school-based sex education programmes in
      sub-Saharan Africa. 

PMID- 24441514
TI  - DNA regions responsible for maintenance of Shingobium plasmid pYAN-2.
AB  - We have identified and analyzed two DNA regions responsible for stable
      maintenance of a plasmid in the genus Sphingomonas and Escherichia coli. A 37 bp
      fragment, upstream of the repA gene, is required for stable maintenance of the
      low-copy-number small plasmid pYAN-2 (4,687 bp) from Sphingobium yanoikuyae. It
      does not encode any significant protein sequence and has one direct repeat for
      possible secondary structures. Moreover, a 70 bp fragment, upstream of the above
      sequence, completely stabilized the unstable pSC101 plasmid in E. coli. 

PMID- 24441516
TI  - High-resolution anoscopy screening of HIV-positive MSM: longitudinal results from
      a pilot study.
AB  - BACKGROUND: The ability to detect and treat pre-malignant anal lesions suggests
      screening may prevent anal cancer. The incidence of anal cancer in men who have
      sex with men (MSM) living with HIV exceeds that of cervical cancer before
      screening was introduced. METHODS: High-resolution anoscopy (HRA) with
      intervention for high-grade squamous intraepithelial lesions (HSILs) was offered
      to asymptomatic HIV-positive MSM. Patients with HSILs were treated and follow-up
      HRA performed after 6 months, whilst patients with low-grade squamous
      intraepithelial lesions had a repeat HRA after 12 months. RESULTS: Three hundred
      and sixty-eight asymptomatic MSM had a total of 1497 HRAs during a median follow
      up of 4.2 years (maximum 13 years). At first HRA, 36% had normal appearances, 16%
      had no dysplasia, 15% anal intraepithelial neoplasia (AIN)-1, 19% AIN-2 and 13%
      AIN-3. During follow-up, five patients (1.4%) developed invasive anal cancer
      (incidence 2.7 per 1000 person-years). The 5-year cancer rate for the 368
      patients was 0.3% [95% confidence interval (CI) 0-0.6%]. Progression to cancer
      was associated with higher age (P=0.049) and AIN-3 (P=0.024). Ninety patients had
      AIN-3 present at least at one HRA. The cumulative risk of cancer from first AIN-3
      diagnosis was 3.2% (95% CI 0-7.8%) at 5 years. One hundred and seventy-one
      patients had HSILs (AIN-2 or 3) present at least once. The cumulative risk of
      cancer from first HSIL diagnosis was 0.6% (95% CI 0-1.8%) at 5 years. CONCLUSION:
      AIN-3 is a significant risk factor for subsequent anal cancer, although the
      tumours detected in screened patients were small localized, and generally the
      outcomes were favourable.

PMID- 24441515
TI  - Tolerance of anaerobic bacteria to chlorinated solvents.
AB  - The aim of this research was to evaluate the effects of four chlorinated
      aliphatic hydrocarbons (CAHs), perchloroethene (PCE), carbon tetrachloride (CT),
      chloroform (CF) and 1,2-dichloroethane (1,2-DCA), on the growth of eight
      anaerobic bacteria: four fermentative species (Escherichia coli, Klebsiella sp.,
      Clostridium sp. and Paenibacillus sp.) and four respiring species (Pseudomonas
      aeruginosa, Geobacter sulfurreducens, Shewanella oneidensis and Desulfovibrio
      vulgaris). Effective concentrations of solvents which inhibited growth rates by
      50% (EC50) were determined. The octanol-water partition coefficient or log Po/w
      of a CAH proved a generally satisfactory measure of its toxicity. Most species
      tolerated approximately 3-fold and 10-fold higher concentrations of the two
      relatively more polar CAHs CF and 1,2-DCA, respectively, than the two relatively
      less polar compounds PCE and CT. EC50 values correlated well with growth rates
      observed in solvent-free cultures, with fast-growing organisms displaying higher
      tolerance levels. Overall, fermentative bacteria were more tolerant to CAHs than
      respiring species, with iron- and sulfate-reducing bacteria in particular
      appearing highly sensitive to CAHs. These data extend the current understanding
      of the impact of CAHs on a range of anaerobic bacteria, which will benefit the
      field of bioremediation. 

PMID- 24441517
TI  - [The safety profile of escitalopram in pregnancy and breastfeeding].
AB  - INTRODUCTION: Escitalopram (ESC) is considered one of the most effective
      selective serotonin reuptake inhibitors (SSRI) for the treatment of major
      depression disorder. However, little is known on its potential risk of inducing
      major malformations (MM) and/or perinatal complications (PC). Aim of the present
      study is to provide a review of the available literature on the safety profile of
      ESC during pregnancy and breastfeeding and to compare data with the maternal and
      neonatal outcomes of 8 cases of the DEGRA Center. METHODS: MEDLINE and PubMed
      databases were searched for English language articles by using the following
      keywords: "escitalopram", "selective serotonin reuptake inhibitors", "major
      malformations", "perinatal complications", "pregnancy", "breastfeeding". We also
      reported 8 cases of women treated with ESC during their pregnancy and
      breastfeeding at the Clinic of Affective Disorders in Pregnancy and Postpartum of
      the United Hospital of Ancona (DEGRA Center). RESULTS: Although some cases of MM
      have been reported in the literature after maternal exposure to ESC during early
      pregnancy, the rate of MM is substantially in the range of those reported in
      unexposed women. ESC exposure seems to be significantly associated with some PC
      such as lower rates of live births and higher rates of newborns with low birth
      weight. On the contrary, no short-term adverse effects in newborns were reported
      in the 5 studies evaluating the safety of ESC during breastfeeding. Data coming
      from DEGRA Center are consistent with the literature: all pregnancy were full
      term, all newborns were healthy and obtained normal APGAR score; no MM or
      miscarriage were reported. Only one case of mild withdrawal syndrome was reported
      in a newborn who was also exposed to benzodiazepines and paroxetine late in
      pregnancy. Two infants exposed to ESC also during the lactation did not reported
      any adverse effects at short-term. CONCLUSIONS: Data coming from published
      studies and from our cases seem to support the notion that ESC might be
      considered safe during pregnancy and breastfeeding, particularly as far as MM is
      concerned. As well as other SSRI it could be associated with an increased risk of
      PC. Nevertheless, given the few cases here analysed and the paucity of the
      studies so far published, no definitive conclusions should be drawn.

PMID- 24441518
TI  - [Growing up with congenital heart disease: neurocognitive outcome,
      psychopathology and quality of life].
AB  - Thank to medical and surgical improvements, a very high percentage of children
      with congenital heart disease (CHD; about 1% of newborn) reaches adulthood. This
      population of young surgical and medical patients opens up new challenges in
      clinical management, including evaluation and optimization of psychosocial
      functioning and quality of life. Data regarding neurocognitive and
      psychopathological adaptation, personality and quality of life of CHD patients
      are rather extensive but still insufficient to guide management approaches to
      these subjects and to address the numerous emerging problems. The present review
      analyzes extensively the research literature to find out those variables that may
      influence development of CHD children. It emerges that a multi-factorial process
      seems involved in the poor outcome of neurocognitive development in many
      patients. Notwithstanding the attempts to define risk factors, current researches
      do not consent definitive conclusions about the determinants of developmental
      problems in CHD children. An improvement of existential outcome for CHD subjects
      may be achieved if adequate interventions are carried out. In fact,
      psychopathological and quality of life in CHD subjects may result even better if
      elaboration of disease by CHD subjects is adequately supported. On one hand,
      genetic factors that may contribute to unfavourable evolutions suggest the need
      for early recognition of subjects at risk. On the other, research should be
      addressed to the identification of those protective and risk factors related to
      personality, environmental and relational aspects entailed in the development of
      CHD subjects. 

PMID- 24441519
TI  - [HIV, depression and compliance: the mediating role of cytokines. A review of the
      international literature].
AB  - HIV-positive individuals are at greater risk of depression, which is known to
      influence their well-being negatively. In fact, depression may promote unhealthy
      behaviors (e.g. drug use and intentional unprotected sex); furthermore,
      depression may also act reducing immune system functioning. However, the
      relationship between the immune system and depression is bidirectional, since
      many physchoneuroimmunological research studies have shown that immune system
      activation, more specifically pro-inflammatory cytokines, increases the risk of
      depression. Thus, HIV-positive persons with co-infection (e.g. HCV), taking HAART
      and/or interferon-alpha, may show cytokine dysregulation. This may explain the
      greater prevalence of depression among HIV-positive individuals. In fact, pro
      inflammatory cytokines and cortisol (also known as stress hormone), both promote
      tryptophan depletion, which is commonly associated with depressive symptoms.
      Hence, depression may negatively influence compliance, increasing the risk for
      incorrect assumption of antiretroviral leading to a significant reduction of
      immune system functioning. This review examines the relationship between HIV
      infection, co-infection (e.g., HCV), HAART and/or interferon-alpha therapy and
      cytokine dysregulation, with a focus on the influence of pro-inflammatory
      cytokines in promoting depression, which could ultimately reduce compliance.
      Evidence-based pharmacological and psycho-social interventions on depression are
      also discussed. 

PMID- 24441520
TI  - [Executive function deficits in ADHD and Asperger syndrome].
AB  - BACKGROUND: The aim of this study is to evaluate the executive functioning of
      children with attention deficit hyperactivity disorder combined subtype (ADHD-C)
      and Asperger syndrome (AS) compared to a control group. METHODS: A sample of 79
      children (28 ADHD-C; 24 AS; 27 subjects with typical development) was tested on a
      wide range of tasks related to major domains of executive functioning: inhibition
      response (prepotent and interference), visual working memory, planning and
      cognitive flexibility. RESULTS: Patients with AS showed deficits on visual
      working memory and cognitive flexibility. ADHD-C children were impaired on
      inhibition control (prepotent response) but also showed deficits on working
      memory and cognitive flexibility. The only executive functioning measure that
      differentiated ADHD from AS was inhibition of prepotent response and a more high
      deficit in cognitive flexibility and working memory in AS compared to ADHD-C.
      CONCLUSIONS: This study confirms recent evidence about the identification of
      specific executive profiles in these disorders. Other studies are warranted to
      evaluate the presence and specifity of a dysexecutive syndrome in ADHD and AS in
      a larger sample with girls.

PMID- 24441521
TI  - [ADHD symptoms as risk factors for dysfunctional eating habits in adolescents:
      results from a longitudinal study].
AB  - AIM: The aim of this study is to analyze the relationship between attention
      deficit hyperactivity disorder (ADHD) symptoms in childhood and early-adolescence
      and the development of dysfunctional eating habits later in life. The sample
      under investigation is composed of 217 adolescents (males: 30.9%; mean age: 17.1
      +/- 0.88 ys; range: 16-19 ys) voluntarily recruited in the city of Parma
      (Northern Italy) in the context of a longitudinal research project focused on
      developmental factors of antisocial behaviour. All subjects were assessed at T1
      (mean age: 12 ys) and at T2 (mean age: 14 ys) using a structured clinical
      interview to collect information on ADHD symptoms on a lifetime basis and, at T3
      (mean age: 17 ys), they were administered an interview to assess pathological
      eating habits. Correlation and regression analyses were carried out between
      scores of the three symptom domains of ADHD and eating habits as assessed at T3.
      Results suggest that the association between ADHD symptoms and eating habits show
      differences according to gender, in that in females ADHD symptoms assessed at T2
      are associated with compensatory behaviours, while in males they are predictive
      of overweight as assessed at T3. ADHD symptoms, although under threshold, may
      lead to chaotic and unorganized eating habits which might put female at risk for
      compensatory behaviours and males for overweight.

PMID- 24441523
TI  - Comparative analysis of crystal-field parameters for rare-earth ions at
      monoclinic sites in AB(WO4)2 crystals: II. Pr3+ and Nd3+ ions in KRE(WO4)2 (RE =
      Y or Gd), Pr3+ ions in M+ Bi(XO4)2 (M+ = Li or Na and X = W or Mo), and Nd3+ ions
      in NaBi(WO4)2 and AgNd(WO4)2.
AB  - In part I, the crystal-field (CF) parameter (CFP) sets for important potential
      solid state laser systems Tm(3+), Ho(3+), and Er(3+) ions in KGd(WO4)2 and Tm(3+)
      ions in KLu(WO4)2 were thoroughly revisited using a general framework for the
      analysis of CF levels and CFP modeling. In this part the non-standard CFP sets
      for Pr(3+) and Nd(3+) ions in KR(WO4)2 (R = Y or Gd) and the standard CFP sets
      for Pr(3+) ions in M(+)Bi(XO4)2 (M(+) = Li or Na and X = W or Mo) and Nd(3+) ions
      in the related systems NaBi(WO4)2 and AgNd(WO4)2 are analyzed. Due to structural
      similarity of the hosts, the CFP values for a given trivalent rare-earth (RE(3+))
      ion should be quite close in these systems. However, the fitted (and model) CFP
      sets appear disparate for the systems in question. The standardization criteria
      are utilized to ensure direct comparability of the apparently disparate CFP sets
      reported in the literature. The CFP sets standardized by us are compared with the
      originally standard CFP sets for Pr(3+) and Nd(3+) ions in related AB(XO4)2
      systems. Following part I, we argue that meaningful analysis of the mixed CFP
      sets, i.e. standard and non-standard ones, must take into account the intrinsic
      features of CF Hamiltonians for orthorhombic and lower symmetry cases, which have
      not been fully recognized in the literature as yet. The model or fitted CFP sets
      that belong to disparate regions in the CFP space are intrinsically incompatible,
      i.e. such sets should not be directly compared. The correlated alternative CFP
      sets are calculated using monoclinic standardization transformations. The
      closeness of the standardized CFP sets is assessed in a quantitative way using
      the closeness factors and the norms ratios. Comparative analysis of the
      monoclinic CFP sets reported for the titled ion-host systems is carried out and
      several inconsistencies in the previous studies are clarified. The CFP sets
      determined by standardization are utilized as starting sets for applications of
      the multiple correlated fitting technique to independently obtain and
      additionally verify the fitted CFPs based on published energy levels data.
      Multiple correlated fittings offer an advantage over the single-fitting tactics
      by enabling an improved fine-tuning of the final fitted CFPs as well as their
      interpretation and comparability with the sets obtained by others. The present
      consistent methodology may enable better understanding of the intricate aspects
      inherent in the spectroscopic studies for other ion-host systems exhibiting
      orthorhombic, monoclinic, and triclinic site symmetry.

PMID- 24441524
TI  - Dissociative electron attachment to N2O using velocity slice imaging.
AB  - The structure and dynamics of the negative ion resonances leading to dissociative
      electron attachment in N2O are studied using the velocity slice imaging
      technique. Distinct momentum distributions are observed in the O(-) channel for
      the dominant resonances below 4 eV which are considerably different than those
      reported so far. Also the relatively weak but distinct resonances at 8.1 eV and
      13.2 eV are studied for their dynamics for the first time. For each of these
      resonances two different channels of dissociation are observed with differing
      angular distributions. 

PMID- 24441522
TI  - Prevalence and correlates of disordered eating in a general population sample:
      the South East London Community Health (SELCoH) study.
AB  - PURPOSE: Disordered eating has been shown to be more prevalent than full eating
      disorders diagnoses. However, research on its prevalence, socio-demographic,
      psychological correlates, and patterns of service use in multi-ethnic samples is
      still limited. This paper explores these associations in a South London-based
      (UK) sample. METHODS: The South East London Community Health (SELCoH) study is a
      general population survey (N = 1,698) of individuals aged 16+. Disordered eating
      was defined as >=2 positive answers at the SCOFF questionnaire. Crude and
      adjusted logistic and multinomial logistic regression models were fit to
      investigate associations between socio-demographic characteristics, disordered
      eating, psychiatric comorbidity, and service use. RESULTS: A total of 164 (10 %)
      participants reported disordered eating and the majority were from ethnic
      minorities. In adjusted models, Asian ethnicity was associated with purging, loss
      of control eating and preoccupation with food. Individuals with disordered eating
      had higher odds of screening positive for post-traumatic stress disorder and
      personality disorders and of having anxiety/mood disorders, suicidal
      ideation/attempts, hazardous levels of drinking, and used drugs in the previous
      year. Only 36 % of individuals with disordered eating had sought professional
      help in the previous 12 months mostly through their general practitioner (27.4
      %), followed by psychotherapists (12.8 %) and mental health specialists (5.5 %).
      CONCLUSION: This study found a high prevalence of disordered eating, especially
      amongst ethnic minorities, and associations with a number of psychiatric
      conditions. Overall few participants accessed specialist services. These findings
      suggest that both disordered eating manifestations amongst ethnic minorities and
      access to care need better investigation.

PMID- 24441525
TI  - Antibiotic resistance, plasmid-mediated quinolone resistance (PMQR) genes and
      ampC gene in two typical municipal wastewater treatment plants.
AB  - Antibiotic resistant bacteria and plasmid-mediated quinolone resistance genes and
      ampC gene were investigated for Escherichia coli isolates from two typical
      municipal wastewater treatment plants in both dry and wet seasons by using the
      antibiotic susceptibility test and PCR assay, respectively. The results showed
      that 98.4% of the isolates (1056) were found resistant to antibiotic(s) tested
      and 90.6% showed multiple resistances to at least three antibiotics. Tetracycline
      was found to have the highest resistance frequency (70.8%), followed by
      ampicillin (65.1%), whereas ceftazidime had the lowest resistance frequency of
      9.0%. Moreover, 39.2% of the E. coli isolates were carrying plasmids. intI1 had
      the highest detection rate in the plasmids (38.1%), followed by qnrS, ampC, qnrB,
      intI2 and aac(6')-Ib-cr. The disinfection process (UV and chlorination) could
      significantly reduce the number of bacteria, but percentage of the resistant
      bacteria, resistance frequency for each antibiotic, MAR index and detection rate
      of the plasmid-mediated resistance genes were all found increasing in the
      effluents of biological units. The results of this study showed that a more
      frequent horizontal gene transfer occurred in the biological units. Wastewater
      treatment plants were an important medium for the recombination and dissemination
      of antibiotic resistance genes in the environment. 

PMID- 24441526
TI  - Treatment of Hodgkin lymphoma: a 50-year perspective.

PMID- 24441528
TI  - From the editor.

PMID- 24441527
TI  - Enhancing nucleotide metabolism protects against mitochondrial dysfunction and
      neurodegeneration in a PINK1 model of Parkinson's disease.
AB  - Mutations in PINK1 cause early-onset Parkinson's disease (PD). Studies in
      Drosophila melanogaster have highlighted mitochondrial dysfunction on loss of
      Pink1 as a central mechanism of PD pathogenesis. Here we show that global
      analysis of transcriptional changes in Drosophila pink1 mutants reveals an
      upregulation of genes involved in nucleotide metabolism, critical for neuronal
      mitochondrial DNA synthesis. These key transcriptional changes were also detected
      in brains of PD patients harbouring PINK1 mutations. We demonstrate that genetic
      enhancement of the nucleotide salvage pathway in neurons of pink1 mutant flies
      rescues mitochondrial impairment. In addition, pharmacological approaches
      enhancing nucleotide pools reduce mitochondrial dysfunction caused by Pink1
      deficiency. We conclude that loss of Pink1 evokes the activation of a previously
      unidentified metabolic reprogramming pathway to increase nucleotide pools and
      promote mitochondrial biogenesis. We propose that targeting strategies enhancing
      nucleotide synthesis pathways may reverse mitochondrial dysfunction and rescue
      neurodegeneration in PD and, potentially, other diseases linked to mitochondrial
      impairment. 

PMID- 24441529
TI  - Multiple sclerosis: Etiology, incidence and prevalence.
AB  - The article examines the medical, psychological, and social aspects of multiple
      sclerosis (MS), one of the most common neurological disorders in the Western
      hemisphere. It presents current information concerning the symptomology,
      diagnosis, course, progression, and treatment of the illness. 

PMID- 24441530
TI  - Health status, work impediments, and coping related to work roles of women with
      multiple sclerosis.
AB  - This study, guided by stress-appraisal and coping theory, compared health status,
      perceived impediments to work, and coping strategies used by young (<45 years)
      and middle-age (45-64 years) women with multiple sclerosis (MS) with respect to
      three major work roles (employed, homemaker, unemployed). Subjects, 408 women
      below age 65, completed by mail two measures of health status (activities of
      daily living scale (ADL) and MS-related symptoms scale), work impediments scale,
      and work enhancer scale (a measure of coping strategies). Using ANCOVA with
      control for education and duration of MS since diagnosis, results indicated lower
      ADL functioning and increased MS-related symptoms and work impediments among
      middle-age compared to young women (all P<0.05). For work roles, despite no age
      differences, unemployed women had lower ADL functioning, more motor symptoms, and
      perceived more work impediments than homemakers and employed women (all P<0.05).
      Overall, the unemployed used more work coping strategies than homemakers or
      employed women. Findings from the comparison of women <45 years of age with
      respect to both parent status and work role on health status, perceived work
      impediments, and coping variables are also presented. Knowledge of health status,
      perceived work impediments, and available coping strategies of women with MS with
      respect to their various work roles is essential for health providers in planning
      relevant interventions. 

PMID- 24441531
TI  - Job placement interventions for people with multiple sclerosis.
AB  - The article describes model job placement programs for individuals with multiple
      sclerosis (MS). The primary thesis is that both selective placement and job
      seeking skills training are needed to increase labor force participation in the
      American MS community. Specifically, the authors examine (a) MS Back-to-Work:
      Operation Job Match, (b) the Job Raising Program, (c) the Return-to-Work program,
      and (d) the Career Possibilities Project. 

PMID- 24441532
TI  - Factors associated with unemployment among persons with multiple sclerosis.
AB  - The article examines the high (75%) rate of unemployment among Americans with
      multiple sclerosis (MS). Specifically, it considers the demographic, medical,
      psychological, sociopolitical, and work related aspects of MS which have been
      linked to unemployment. 

PMID- 24441533
TI  - Job retention interventions for persons with multiple sclerosis.
AB  - The paper reviews service initiatives designed to facilitate job retention for
      employees with multiple sclerosis (MS). The thesis is that worksite barriers must
      be removed via reasonable accommodations for persons with MS to continue working
      as the illness progresses. Key elements of barrier removal include (a) needs
      assessments, (b) civil rights information concerning Title I of the Americans
      with Disabilities Act, (c) training on how to request reasonable accommodations
      from one's employer, and (d) consultation with employers. 

PMID- 24441534
TI  - The role of assessment in enhancing the vocational success of people with
      multiple sclerosis.
AB  - The person/environment or ecological perspective on vocational evaluation
      provides a comprehensive assessment strategy for people with multiple sclerosis.
      The ecological model requires assessment of both personal variables such as
      rehabilitation outlook and MS symptoms and environmental variables such as
      barriers to workplace accessibility and performance of essential job functions.
      Measures of person and environment constructs are presented as are applications
      of the resulting information in vocational counseling and disability management
      services. 

PMID- 24441535
TI  - Goal oriented inpatient multiple sclerosis group.

PMID- 24441538
TI  - Contents of journals relating to work.

PMID- 24441536
TI  - Employment and multiple sclerosis: Policy, programming, and research
      recommendations.
AB  - The article presents recommendations for policymakers, service providers, and
      consumers to improve the bleak career development prospects for Americans with
      multiple sclerosis (MS). It suggests intervention strategies, research
      initiatives, and information dissemination activities for future consideration. 

PMID- 24441541
TI  - Volume contentsVolume 6 (1996).

PMID- 24441543
TI  - Electrochemiluminescence aptasensor based on bipolar electrode for detection of
      adenosine in cancer cells.
AB  - Here we report a novel approach for the detection of adenosine in cancer cells by
      electrochemiluminescence (ECL) on a wireless indium tin oxide bipolar electrode
      (BPE). In this approach, ferrocene (Fc) which is labeled on adenosine aptamer is
      enriched on one pole of the BPE by hybridization with its complementary DNA
      (ssDNA) and oxidized to Fc(+) under an external voltage of 5.0V at the two ends
      of BPE. Then, a reversed external voltage was added on the BPE, making Fc(+)
      enriched pole as cathode. The presence of Fc(+) promotes the oxidation reaction
      on the anodic pole of the BPE, resulting in a significant increase of ECL
      intensity using Ru(bpy)3(2+)/tripropylamine (TPA) system as test solution. The
      presence of target adenosine was reflected by the ECL signal decrease on the
      anodic pole caused by the target-induced removal of ferrocene-aptamer on the
      cathodic pole. The decrease of ECL signal was logarithmically linear with the
      concentration of ATP in a wide range from 1.0 fM to 0.10 MUM. This ECL biosensing
      system could accurately detect the level of adenosine released from cancer cells.

PMID- 24441542
TI  - Electrochemical sensor based on carbon-supported NiCoO2 nanoparticles for
      selective detection of ascorbic acid.
AB  - An electrochemical sensor for selective detection of ascorbic acid (AA) in the
      presence of dopamine (DA) and uric acid (UA) was fabricated by modifying the
      glassy carbon electrode (GCE) with carbon-supported NiCoO2 (NiCoO2/C)
      nanoparticles. The electrochemical impedance spectroscopic (EIS) studies reveal
      the little charge transfer resistance for the modified electrode. The
      electrocatalytic activity of the modified electrode for the oxidation of AA was
      investigated. The current sensitivity of AA was enhanced to about five times upon
      modification. The voltammetric response of AA was well resolved from the
      responses of DA and UA, and the oxidation potential of AA was negatively shifted
      to -0.20 V. The biosensor tolerated a wide linear concentration range for AA,
      from 1.0 * 10(-5)M to 2.63 * 10(-3)M (R(2)=0.9929), with a detection limit of 0.5
      MUM (S/N = 3). Our results demonstrate that the NiCoO2/C nanomaterials has
      excellent AA sensing capability, including a fast response time, high
      reproducibility and stability, with great promise in the quantification of AA in
      real samples. That makes it a unique electrochemical sensor for the detection of
      AA which is free from the interference of DA, UA and other interferents.

PMID- 24441544
TI  - In-situ detection of density alteration in non-physiological cells with
      polarimetric tilted fiber grating sensors.
AB  - Tilted fiber Bragg grating (TFBG) biosensors can be used as a cost-effective and
      relatively simple-to-implement alternative to well established biosensor
      platforms for high sensitivity biological sample measurements in situ or possibly
      in vivo. The fiber biosensor presented in this study utilizes an in-fiber 12
      degrees  tilted Bragg grating to excite a strong evanescent field on the surface
      of the sensor over a large range of external medium refractive indices. The
      devices have minimal cross-sensitivity to temperature and their fabrication does
      not impact the structural integrity of the fiber and its surface
      functionalization. Human acute leukemia cells with different intracellular
      densities and refractive index (RI) ranging from 1.3342 to 1.3344 were clearly
      discriminated in-situ by using the differential transmission spectrum between two
      orthogonal polarizations for the last guided mode resonance before "cut-off",
      with an amplitude variation sensitivity of 1.8 * 10(4) dB/RIU, a wavelength shift
      sensitivity of 180 nm/RIU, and a limit of detection of 2 * 10(-5)RIU. The
      detection process was precisely controlled with a micro-fluidic chip which allows
      the measurement of nL-volumes of bio-samples. The proposed in-fiber polarimetric
      biosensor is an appealing solution for rapid, sub-microliter dose and highly
      sensitive detection of analytes at low concentrations in medicine, chemical and
      environmental monitoring.

PMID- 24441545
TI  - Mechanisms in cardiac fibroblast growth: an obligate role for Skp2 and FOXO3a in
      ERK1/2 MAPK-dependent regulation of p27kip1.
AB  - Cardiac fibroblast hyperplasia associated with enhanced matrix deposition is a
      major determinant of tissue remodeling in several disease states of the heart.
      However, mechanisms controlling cell cycle progression in cardiac fibroblasts
      remain unexplored. Identification of cell cycle regulatory elements in these
      cells is important to develop strategies to check adverse cardiac remodeling
      under pathological conditions. This study sought to probe the mechanisms
      underlying ERK1/2-mediated p27(Kip1) regulation in mitogenically stimulated
      cardiac fibroblasts. Addition of 10% fetal calf serum to quiescent cultures of
      adult rat cardiac fibroblasts promoted ERK1/2 activation, as evidenced by its
      phosphorylation status. Reduction in [(3)H]thymidine incorporation into DNA
      increased population doubling time, flow cytometry, and Western blot analysis
      showing reduced levels of cyclins D and A, p27(Kip1) induction, and
      retinoblastoma protein (Rb) hypophosphorylation in ERK1/2-inhibited cells
      indicated ERK1/2 dependence of G1-S transition in cardiac fibroblasts. Lack of
      p27(Kip1) protein in serum-stimulated, ERK1/2-active cells was associated with
      increased levels of Skp2, an E3 ubiquitin ligase for p27(Kip1), whose knockdown
      by RNA interference induced p27(Kip1) expression. Further, forced expression of
      Skp2 in ERK1/2-inhibited cells downregulated p27(Kip1). Transcriptional
      upregulation of p27(Kip1) mRNA in ERK1/2-inhibited cells, demonstrated by real
      time PCR, correlated with forkhead box O 3a (FOXO3a) transcription factor
      activation, shown by gel shift assay. FOXO3a knockdown attenuated p27(Kip1) mRNA
      and protein expression in ERK1/2-inhibited cells. We provide evidence for the
      first time that, in cardiac fibroblasts, activated ERK1/2 regulates p27(Kip1)
      expression transcriptionally and posttranslationally via FOXO3a- and Skp2
      dependent mechanisms. Additionally, this study uncovers interesting interactions
      between critical cell cycle regulatory elements that are only beginning to be
      understood. 

PMID- 24441546
TI  - The relationship between longitudinal, lateral, and septal contribution to stroke
      volume in patients with pulmonary regurgitation and healthy volunteers.
AB  - Septal systolic motion is towards the left ventricle (LV) in healthy hearts.
      Patients with pulmonary regurgitation (PR) and right ventricular (RV) volume
      overload have systolic septal motion toward the RV. This may affect the
      longitudinal contribution from atrioventricular plane displacement (AVPD) and
      septal and lateral contribution to stroke volume (SV). The study aimed to
      quantify these contributions to SV in patients with PR. Cardiac magnetic
      resonance imaging was used for assessment of cardiac volumes. Patients (n = 30;
      age 9-59 yr) with PR due to surgically corrected tetralogy of Fallot and 54
      healthy controls (age 10-66 yr) were studied. Longitudinal contribution to RVSV
      was 47 +/- 2% (means +/- SE) in patients with PR and 79 +/- 1% in controls (P <
      0.001). Lateral contribution to RVSV and LVSV was 40 +/- 1 and 62 +/- 2% in
      patients and 31 +/- 1 and 36 +/- 1% in controls (P < 0.001 for both). Septal
      motion contributed to RVSV by 8 +/- 1% in patients and by 7 +/- 1% to LVSV in
      controls (P < 0.001). PR patients have decreased longitudinal contribution to
      RVSV and increased lateral pumping, resulting in larger outer volume changes and
      septal motion towards the RV. The changes in RV pumping physiology may be
      explained by RV remodeling resulting in lower systolic inflow of blood into the
      right atrium in relation to SV. This avoids the development of pendulum volume
      between the caval veins and right atrium, which would occur in PR patients if
      longitudinal contribution to SV was preserved. Decreased AVPD suggests that
      tricuspid annular excursion, a marker of RV function, is less valid in these
      patients. 

PMID- 24441547
TI  - Postconditioning leads to an increase in protein S-nitrosylation.
AB  - Previous studies have shown a role for nitric oxide and S-nitrosylation (SNO) in
      postconditioning (PostC), but specific SNO proteins and sites have not been
      identified in the myocardium after PostC. In this study, we examined SNO
      signaling in PostC using a Langendorff-perfused mouse heart model. After 20 min
      of equilibrium perfusion and 25 min of global ischemia, PostC was applied at the
      beginning of reperfusion with six cycles of 10 s of reperfusion and 10 s of
      ischemia. The total period of reperfusion was 90 min. Compared with the ischemia
      reperfusion (I/R) control, PostC significantly reduced postischemic contractile
      dysfunction and infarct size. PostC-induced protection was blocked by treatment
      with N(G)-nitro-l-arginine methyl ester (l-NAME) (10 MUmol/l; a constitutive NO
      synthase inhibitor), but not by either ODQ (10 MUmol/l, a highly selective
      soluble guanylyl cyclase inhibitor) or KT5823 (1 MUmol/l, a specific protein
      kinase G inhibitor). Two biotin switch based methods, two dimensional CyDye
      maleimide difference gel electrophoresis (2D CyDye-maleimide DIGE) and SNO-resin
      assisted capture (SNO-RAC), were utilized to identify SNO-modified proteins and
      sites. Using 2D CyDye-maleimide DIGE analysis, PostC was found to cause a 25% or
      greater increase in SNO of a number of proteins, which was blocked by treatment
      with l-NAME in parallel with the loss of protection. Using SNO-RAC, we identified
      77 unique proteins with SNO sites after PostC. These results suggest that NO
      mediated SNO signaling is involved in PostC-induced cardioprotection and these
      data provide the first set of candidate SNO proteins in PostC hearts. 

PMID- 24441549
TI  - Cleavage of IkappaBalpha by calpain induces myocardial NF-kappaB activation, TNF
      alpha expression, and cardiac dysfunction in septic mice.
AB  - Recent studies in septic models have shown that myocardial calpain activity and
      TNF-alpha expression increase during sepsis and that inhibition of calpain
      activation downregulates myocardial TNF-alpha expression and improves cardiac
      dysfunction. However, the mechanism underlying this pathological process is
      unclear. Thus, in the present study, we aimed to explore whether IkappaBalpha/NF
      kappaB signaling linked myocardial calpain activity and TNF-alpha expression in
      septic mice. Adult male mice were injected with LPS (4 mg/kg ip) to induce
      sepsis. Myocardial calpain activity, IkappaBalpha/NF-kappaB signaling activity,
      and TNF-alpha expression were assessed, and myocardial function was evaluated
      using the Langendorff system. In septic mice, myocardial calpain activity and TNF
      alpha expression were increased and IkappaBalpha protein was degraded.
      Furthermore, NF-kappaB was activated, as indicated by increased NF-kappaB p65
      phosphorylation, cleavage of p105 into p50, and its nuclear translocation.
      Administration of the calpain inhibitors calpain inhibitor SH and PD-150606
      prevented the LPS-induced degradation of myocardial IkappaBalpha, NF-kappaB
      activation, and TNF-alpha expression and ultimately improved myocardial function.
      In calpastatin transgenic mice, an endogenous calpain inhibitor and cultured
      neonatal mouse cardiomyocytes overexpressing calpastatin also inhibited calpain
      activity, IkappaBalpha protein degradation, and NF-kappaB activation after LPS
      treatment. In conclusion, myocardial calpain activity was increased in septic
      mice. Calpain induced myocardial NF-kappaB activation, TNF-alpha expression, and
      myocardial dysfunction in septic mice through IkappaBalpha protein cleavage. 

PMID- 24441548
TI  - NFAT transcription factor regulation by urocortin II in cardiac myocytes and
      heart failure.
AB  - Urocortin II (UcnII), a cardioactive peptide with beneficial effects in normal
      and failing hearts, is also arrhythmogenic and prohypertrophic. We demonstrated
      that cardiac effects are mediated by a phosphatidylinositol-3 kinase (PI3K)/Akt
      kinase (Akt)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling
      pathways. Nuclear factor of activated T-cells (NFAT) transcription factors play a
      key role in the regulation of gene expression in cardiac development, maintenance
      of an adult differentiated cardiac phenotype, and remodeling processes in cardiac
      hypertrophy and heart failure (HF). We tested the hypothesis that UcnII
      differentially regulates NFAT activity in cardiac myocytes from both normal and
      failing hearts through the PI3K/Akt/eNOS/NO pathway. Isoforms NFATc1 and NFATc3
      revealed different basal subcellular distribution in normal and HF rabbit
      ventricular myocytes with a nuclear NFATc1 and a cytosolic localization of
      NFATc3. However, in HF, the nuclear localization of NFATc1 was less pronounced,
      whereas the nuclear occupancy of NFATc3 was increased. In normal myocytes, UcnII
      induced nuclear export of NFATc1 and attenuated NFAT-dependent transcriptional
      activity but did not affect the distribution of NFATc3. In HF UcnII facilitated
      nuclear export of both isoforms and reduced transcriptional activity. NFAT
      regulation was mediated by a PI3K/Akt/eNOS/NO signaling cascade that converged on
      the activation of several kinases, including glycogen synthase kinase-3beta
      (GSK3beta), c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated kinase (p38),
      and PKG, resulting in phosphorylation, deactivation, and nuclear export of NFAT.
      In conclusion, while NFATc1 and NFATc3 reveal distinct subcellular distribution
      patterns, both are regulated by the UcnII-PI3K/Akt/eNOS/NO pathway that converges
      on the activation of NFAT kinases and NFAT inactivation. The data reconcile
      cardioprotective and prohypertrophic UcnII effects mediated by different NFAT
      isoforms. 

PMID- 24441552
TI  - From the editor.

PMID- 24441553
TI  - Activity performance, life satisfaction and locus of control in young women on
      sick leave.
AB  - OBJECTIVES: (1) To elucidate the impact of long-term sick leave on activity
      patterns, life roles and life satisfaction in younger women; and (2) to deduce
      the locus of control orientation in these women. STUDY DESIGN: Twelve women aged
      21-30 years were interviewed in their own home concerning activities in daily
      life, family and work situations. A questionnaire containing checklists on
      activity preferences, occupational roles, life satisfaction, and locus of control
      was mailed to the participants prior to the interview. RESULTS: Most of the women
      experienced restrictions in their activity pattern. Six of the women reported
      that they did not possess a role as a worker, while the majority had and
      appreciated the roles as home-maintainer, partner, family member and friend. Six
      of the women were satisfied with life as a whole. Only two were satisfied with
      vocational and financial situations. The mean value of locus of control indicates
      an external orientation. CONCLUSIONS: Rehabilitation interventions for these
      clients need to be broad and problem-oriented. Occupational therapists seem to
      have an important role in assisting in the restoration of a more satisfactory
      life.

PMID- 24441554
TI  - Schooling, work satisfaction and productivity: an examination of Jeremy Bentham.
AB  - This paper examines the ethical dimensions of work productivity and work
      satisfaction. This issue is explored by looking at the ethical theory of Jeremy
      Bentham. He argues that work satisfaction is so highly subjective and personal
      that we can school people to experience work satisfaction when in the most
      distasteful jobs. Bentham argues that, from the perspective of the principle of
      utility, there is nothing wrong with schooling some people to experience work
      satisfaction from what seems like distasteful work. This paper suggests that
      Bentham's theory justifies class relationship and flies in the face of the notion
      of equality of job opportunity. 

PMID- 24441550
TI  - beta-Adrenergic blockade enhances coronary vasoconstrictor response to forehead
      cooling.
AB  - Forehead cooling activates the sympathetic nervous system and can trigger angina
      pectoris in susceptible individuals. However, the effect of forehead cooling on
      coronary blood flow velocity (CBV) is not well understood. In this human
      experiment, we tested the hypotheses that forehead cooling reduces CBV (i.e.,
      coronary vasoconstriction) and that this vasoconstrictor effect would be enhanced
      under systemic beta-adrenergic blockade. A total of 30 healthy subjects (age
      range, 23-79 years) underwent Doppler echocardiography evaluation of CBV in
      response to 60 s of forehead cooling (1 degrees C ice bag on forehead). A subset
      of subjects (n = 10) also underwent the procedures after an intravenous infusion
      of propranolol. Rate pressure product (RPP) was used as an index of myocardial
      oxygen demand. Consistent with our first hypothesis, forehead cooling reduced CBV
      from 19.5 +/- 0.7 to 17.5 +/- 0.8 cm/s (P < 0.001), whereas mean arterial
      pressure increased by 11 +/- 2 mmHg (P < 0.001). Consistent with our second
      hypothesis, forehead cooling reduced CBV under propranolol despite a significant
      rise in RPP. The current studies indicate that forehead cooling elicits a
      sympathetically mediated pressor response and a reduction in CBV, and this effect
      is augmented under beta-blockade. The results are consistent with sympathetic
      activation of beta-receptor coronary vasodilation in humans, as has been
      demonstrated in animals. 

PMID- 24441555
TI  - Violence in the Swedish school environment: extent of the problem and its
      manifestations.
AB  - The current importance of school violence due to its recent increase, and also
      its association with school-specific psychosocial and physical environmental
      problems were considered as part of a recent survey of Swedish public-sector
      schools. The responses of the principals of a representative sample of schools
      (68.4% response rate) revealed that, for the school year 1995-1996, violence was
      a problem regarded as 'moderate' or 'large' in 15% of schools, 'small' in 62%,
      and as 'non-significant' in 20%. There has been a non-uniform trend in
      perceptions of violence across types of schools and municipalities since 1990.
      Schools where violence has been a problem for some time were more likely to
      express dissatisfaction with the psychosocial and physical environment of the
      school, and to emphasize individual and adult-supervision factors as injury
      determinants. Prevention of intentional injuries requires a variety of
      interventions, adapted according to factors associated with the problem at local
      level. 

PMID- 24441556
TI  - Stress, coping and the job search process: the experience of people with
      psychiatric disabilities in supported employment.
AB  - Ten people with psychiatric disabilities and their supported employment
      coordinators responded to a standardized, open-ended interview about the stresses
      experienced during the job search process and the coping strategies used to deal
      with these stresses. The stress inherent in the potential for rejection and
      negative valuation was a major theme. The respondents described both problem
      based and emotion focused coping strategies. The people with psychiatric
      disabilities also identified cognitive strategies they employ to maintain their
      motivation and ego integrity. While these cognitive strategies are used to
      neutralize the impact of a stress, they can be a source of tension within the
      rehabilitation relationship. Current conceptualizations may not adequately
      address the struggles inherent in the job search process. 

PMID- 24441557
TI  - The effectiveness of feedback in improving safe behaviors: a review of the
      literature.
AB  - Reducing unsafe behaviors in the work place is of primary concern in industry.
      Unsafe behaviors seem to be shaped both by a subtle reinforcement of these
      behaviors by the work culture and by management's failure to define what
      constitutes unsafe behavior. Thus, any program to change these behaviors must
      focus both on defining and reinforcing safe behaviors. This paper reviews some of
      the literature associated with feedback and its effectiveness in increasing
      worker safety. The Theory of Planned Behavior is discussed as one possible
      mechanism for explaining the positive results achieved. 

PMID- 24441558
TI  - The differences in perception of wheelchair performance between direct care and
      professional staff on a residential unit for individuals with severe
      developmental disabilities.
AB  - A pilot study was conducted on a residential unit in an institution for
      individuals with severe multiple physical and mental disabilities in order to
      compare the perceptions of direct care and professional staff members on the
      functional performance of wheelchairs. The study was a part of a collaborative
      research project with the OMRDD and School of Education, New York University that
      focused on enhancing the quality of life of those disabled individuals through
      the application of assistive technology. The results of the study showed a
      considerable discrepancy in the perceptions of wheelchair functional performance
      between two categories of care providers on the unit. The members of the direct
      care staff perceived the wheelchairs as low functioning in contrast to the
      members of the professional staff who perceived the same wheelchairs to be close
      to fully functional. The possible causes of the differences between the members
      of both categories of care providers on the unit regarding the functional
      performance of wheelchairs and their accommodation to the specific needs of the
      clients are discussed. 

PMID- 24441559
TI  - A clinician's guide to work-related assessments: 1 - purposes and problems.
AB  - This paper is the first of a series aimed at providing clinicians with a guide to
      assist them in using work-related assessments appropriately. The context of work
      related assessments is described using a model. The purposes of work-related
      assessments are classified and discussed using the proposed model. The 10 major
      problems facing clinicians using work-related assessments are outlined. Companion
      papers describe the design, administration and interpretation problems in detail.

PMID- 24441560
TI  - A clinician's guide to work-related assessments: 2 - design problems.
AB  - This paper is the second in a series aimed at providing clinicians with a guide
      to assist them in using work-related assessments appropriately. This paper
      discusses the four major design problems facing clinicians using work-related
      assessments. These problems are: (1) a confused definition of terms; (2) confused
      conceptual basis; (3) separation of the individual from the context and the
      environment; and (4) lack of assessment of psychosocial/cognitive aspects related
      to work. Suggestions are provided to assist clinicians in making decisions
      regarding work-related assessments. Recommendations for further research to
      ameliorate these problems are also made. Companion papers describe the purposes
      of work-related assessments, and administration and interpretation problems in
      detail. 

PMID- 24441561
TI  - A clinician's guide to work-related assessments: 3 - Administration and
      interpretation problems.
AB  - This paper is the third of a series aimed at providing clinicians with a guide to
      assist them in using work-related assessments appropriately. The major
      administration and interpretation problems facing clinicians using work-related
      assessments are described in detail. Administration problems are: (1)
      insufficient evidence of reliability and validity; and (2) potential examiner
      bias. Interpretation problems are: (1) inappropriate use of norm and criterion
      referenced data; (2) inappropriate statistical manipulation of results; (3)
      difficulty in determining end-point; and (4) difficulty determining sincerity of
      effort. Companion papers describe the purposes of work-related assessments, and
      design problems in detail. 

PMID- 24441562
TI  - The effectiveness of different intervention strategies in preventing back pain in
      members of the nursing population and the general population.
AB  - The effectiveness of different intervention strategies for preventing back pain
      was investigated. Due to physical job demands, nursing personnel appear to be at
      greater risk for back problems than the general population. This literature
      review examines various studies, to compare the effectiveness of intervention
      programs between nursing personnel and the general public. This review compares
      the effectiveness of two main forms of interventions reported in the literature:
      education and exercise based programs. Different styles of implementation (hands
      on vs. observational) are further examined. Despite mixed results, a review of
      the literature indicates that an exercise-based program offers promising results.
      Although greater uncertainty is seen in education-based interventions, an
      interactive approach is suggested for such a program. Implications for future
      areas of research are discussed. 

PMID- 24441563
TI  - Prevention of cumulative trauma disorders: a role for occupational therapists in
      the schools.

PMID- 24441565
TI  - Ullmann-type coupling of brominated tetrathienoanthracene on copper and silver.
AB  - We report the synthesis of extended two-dimensional organic networks on Cu(111),
      Ag(111), Cu(110), and Ag(110) from thiophene-based molecules. A combination of
      scanning tunnelling microscopy and X-ray photoemission spectroscopy yields
      insight into the reaction pathways from single molecules towards the formation of
      two-dimensional organometallic and polymeric structures via Ullmann reaction
      dehalogenation and C-C coupling. The thermal stability of the molecular networks
      is probed by annealing at elevated temperatures of up to 500  degrees C. On
      Cu(111) only organometallic structures are formed, while on Ag(111) both
      organometallic and covalent polymeric networks were found to coexist. The ratio
      between organometallic and covalent bonds could be controlled by means of the
      annealing temperature. The thiophene moieties start degrading at 200  degrees C
      on the copper surface, whereas on silver the degradation process becomes
      significant only at 400  degrees C. Our work reveals how the interplay of a
      specific surface type and temperature steers the formation of organometallic and
      polymeric networks and describes how these factors influence the structural
      integrity of two-dimensional organic networks. 

PMID- 24441566
TI  - Gold nanoparticle assemblies stabilized by bis(phthalocyaninato)lanthanide(III)
      complexes through van der Waals interactions.
AB  - Gold nanoparticle assemblies possess diverse application potential, ranging from
      industrial nanotechnology to medical biotechnology. Because the structures and
      properties of assemblies are directly affected by the stabilization mechanism
      between the organic molecules serving as protecting ligands and the gold
      nanoparticle surface, it is crucial to find and investigate new stabilization
      mechanisms. Here, we report that pi-conjugated phthalocyanine rings can serve as
      stabilizing ligands for gold nanoparticles. Bis(phthalocyaninato)lutetium(III)
      (LuPc2) or bis(phthalocyaninato)terbium(III) (TbPc2), even though complex, do not
      have specific binding units and stabilize gold nanoparticles through van der
      Waals interaction between parallel adsorbed phthalocyanine ligands and the gold
      nanoparticle surface. AC magnetic measurements and the electron-transport
      properties of the assemblies give direct evidence that the phthalocyanines are
      isolated from each other. Each nanoparticle shows weak electronic coupling
      despite the short internanoparticle distance (~1 nm), suggesting Efros-Shklovskii
      type variable-range hopping and collective single-electron tunnelling behaviours.

PMID- 24441567
TI  - Mesoscale characterization of supramolecular transient networks using SAXS and
      rheology.
AB  - Hydrogels and, in particular, supramolecular hydrogels show promising properties
      for application in regenerative medicine because of their ability to adapt to the
      natural environment these materials are brought into. However, only few studies
      focus on the structure-property relationships in supramolecular hydrogels. Here,
      we study in detail both the structure and the mechanical properties of such a
      network, composed of poly(ethylene glycol), end-functionalized with ureido
      pyrimidinone fourfold hydrogen bonding units. This network is responsive to
      triggers such as concentration, temperature and pH. To obtain more insight into
      the sol-gel transition of the system, both rheology and small-angle X-ray
      scattering (SAXS) are used. We show that the sol-gel transitions based on these
      three triggers, as measured by rheology, coincide with the appearance of a
      structural feature in SAXS. We attribute this feature to the presence of
      hydrophobic domains where cross-links are formed. These results provide more
      insight into the mechanism of network formation in these materials, which can be
      exploited for tailoring their behavior for biomedical applications, where one of
      the triggers discussed might be used. 

PMID- 24441569
TI  - Artesunate reduces serum lipopolysaccharide in cecal ligation/puncture mice via
      enhanced LPS internalization by macrophages through increased mRNA expression of
      scavenger receptors.
AB  - Innate immunity is the first line of defense in human beings against pathogen
      infection; monocytes/macrophages are the primary cells of the innate immune
      system. Recently, macrophages/monocytes have been discovered to participate in
      LPS clearance, and the clearance efficiency determines the magnitude of the
      inflammatory response and subsequent organ injury. Previously, we reported that
      artesunate (AS) protected sepsis mice against heat-killed E. coli challenge.
      Herein, we further confirmed that AS protected cecal ligation/puncture (CLP)
      sepsis mice. Its protection on sepsis mice was related to not only reduction of
      pro-inflammatory cytokines and serum LPS levels but also improvement of liver
      function. Based on the fact that AS did not directly bind and neutralize LPS, we
      hypothesized that the reduction of serum LPS level might be related to
      enhancement of LPS internalization and subsequent detoxification. Our results
      showed that AS increased FITC-LPS internalization by peritoneal macrophage and
      liver Kupffer cell, but enhancement of LPS internalization by AS was not related
      to the clathrin-dependent pathway. However, AS induced mRNA expression of
      important scavenger receptors (SRs); SR-A and MARCO mRNA expression was
      upregulated, suggesting that AS enhancement of LPS internalization and inhibition
      of pro-inflammatory cytokines was related to changes in mRNA expression of SRs. 

PMID- 24441570
TI  - Optimization and evaluation of magnetic bead separation combined with matrix
      assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF
      MS) for proteins profiling of peritoneal dialysis effluent.
AB  - Peritoneal dialysis effluent (PDE) potentially carries an archive of peptides
      relevant to pathological processes in abdominal and surrounding tissues. Magnetic
      beads and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry is one such approach that offers a unique tool for profiling of
      peptides, but this approach has not been used in the PDE analysis. In this study,
      we developed a strategy for screening PDE proteins <15 kDa and applied this
      technique to identify potential biomarkers for peritonitis. We examined four
      kinds of magnetic beads, including a carbon series (C3, C8), weak cation exchange
      (WCX) and immobilized metal-affinity chromatography (IMAC-Cu) beads. Samples
      processed with IMAC-Cu magnetic beads consistently showed more MS signals across
      all beads within the measured mass range. Moreover, there was no difference in
      the number and morphology of MS signals between concentrated and unconcentrated
      samples. The PDE peptidome pattern, based on a panel of 15 peaks, accurately
      recognized peritonitis PD patients from peritonitis-free patients with
      sensitivity of 90.5% and specificity of 94.7% respectively. Therefore, IMAC-Cu
      magnetic beads and unconcentrated samples can be used as a fast and cost
      effective approach for sample preparation prior to more in-depth discovery of
      predictive biomarkers of disease in patients on dialysis. 

PMID- 24441568
TI  - G protein-coupled receptors: what a difference a 'partner' makes.
AB  - G protein-coupled receptors (GPCRs) are important cell signaling mediators,
      involved in essential physiological processes. GPCRs respond to a wide variety of
      ligands from light to large macromolecules, including hormones and small
      peptides. Unfortunately, mutations and dysregulation of GPCRs that induce a loss
      of function or alter expression can lead to disorders that are sometimes lethal.
      Therefore, the expression, trafficking, signaling and desensitization of GPCRs
      must be tightly regulated by different cellular systems to prevent disease.
      Although there is substantial knowledge regarding the mechanisms that regulate
      the desensitization and down-regulation of GPCRs, less is known about the
      mechanisms that regulate the trafficking and cell-surface expression of newly
      synthesized GPCRs. More recently, there is accumulating evidence that suggests
      certain GPCRs are able to interact with specific proteins that can completely
      change their fate and function. These interactions add on another level of
      regulation and flexibility between different tissue/cell-types. Here, we review
      some of the main interacting proteins of GPCRs. A greater understanding of the
      mechanisms regulating their interactions may lead to the discovery of new drug
      targets for therapy. 

PMID- 24441571
TI  - Leptin activates RhoA/ROCK pathway to induce cytoskeleton remodeling in nucleus
      pulposus cells.
AB  - Hyperleptinemia is implicated in obesity-associated lumbar disc degeneration.
      Nevertheless, the effect of leptin on the intracellular signaling of nucleus
      pulposus cells is not clear. The current study sought to delineate the possible
      involvement of the RhoA/ROCK pathway in leptin-mediated cytoskeleton
      reorganization in nucleus pulposus cells. Nucleus pulposus cells isolated from
      scoliosis patients were treated with 10 ng/mL of leptin. Fluorescent resonance
      energy transfer analysis was used to determine the activation of RhoA signaling
      in nucleus pulposus cells. The protein expression of LIMK1 and cofilin-2 were
      analyzed by western blot analysis. F-actin cytoskeletal reorganization was
      assessed by rhodamine-conjugated phalloidin immunoprecipitation. Leptin induced F
      actin reorganization and stress fiber formation in nucleus pulposus cells,
      accompanied by localized RhoA activation and phosphorylation of LIMK1 and
      cofilin. The RhoA inhibitor C3 exoenzyme or the ROCK inhibitor Y-27632 potently
      attenuated the effects of leptin on F-actin reorganization and stress fiber
      formation. Both inhibitors also prevented leptin-induced phosphorylation of LIMK1
      and cofilin-2. Our study demonstrated that leptin activated the
      RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in nucleus
      pulposus cells. These findings may provide novel insights into the pathogenic
      mechanism of obesity-associated lumbar disc degeneration. 

PMID- 24441572
TI  - Tibial tuberosity fracture as a complication of tibial tuberosity advancement.
AB  - OBJECTIVES: To retrospectively compare two clinical subsets of dogs suffering
      tibial tuberosity (TT) fracture (incidental finding or sudden onset severe
      lameness) as a complication of tibial tuberosity advancement (TTA) and to report
      the surgical management and outcome of TT fracture as a complication of TTA.
      MATERIAL AND METHODS: The medical records of 10 dogs with eleven TT fractures or
      crest fractures after TTA were reviewed. The outcome and complications were
      determined from clinical and radiographic follow-up examinations. Limb function
      was evaluated between six and 12 weeks postoperatively. Owners were contacted by
      phone for long-term follow-up at least six months after the last examination.
      RESULTS: Four dogs required surgical stabilization and six dogs had conservative
      management. In the surgical group, every case experienced a sudden non-weight
      bearing lameness after the initial TTA surgery. In three of the four cases an
      attempt was made to stabilize the TT and crest fracture while maintaining the TT
      advancement. Postoperative complications were encountered in three of the four
      surgically treated cases. Functional outcome was considered excellent in seven
      cases and good in the other three. CLINICAL SIGNIFICANCE: Tibial tuberosity
      fracture is a complication of TTA that seems to have a favourable prognosis,
      although it can result in significant morbidity and in some cases revision
      surgery may be required.

PMID- 24441573
TI  - Understanding nontypeable Haemophilus influenzae and chronic obstructive
      pulmonary disease.
AB  - PURPOSE OF REVIEW: Bacteria are frequently implicated in acute exacerbations of
      chronic obstructive pulmonary disease (COPD), but their influence on airway
      inflammation remains unclear. This review will focus on nontypeable Haemophilus
      influenzae (NTHi), its impact on host immune responses, and the potential for
      vaccination strategies in COPD. RECENT FINDINGS: NTHi is associated with impaired
      immune function in patients with COPD. Features of the bacterium itself
      potentiate its ability to colonize the lower airways. An imbalance between
      bacterial load and host immunity may lend itself to the development of
      exacerbations. Oral immunotherapy may be a method of augmenting the host immune
      response and could provide protection from exacerbations. SUMMARY: A causal link
      between NTHi and COPD exacerbations has not been clearly established. However,
      colonization of the lower airways by NTHi likely plays a significant role in the
      inflammatory state of COPD.

PMID- 24441574
TI  - Analysis of the anatomical variation of the atrial musculature may predict the
      success of pulmonary electrical isolation.

PMID- 24441575
TI  - Indirect economic impacts of comorbidities on people with heart disease.
AB  - BACKGROUND:  Few studies have assessed the effect of multiple health conditions
      among patients with heart disease, particularly the economic implications of
      having multiple conditions. METHODS AND RESULTS:  This study used a
      microsimulation model, Health&WealthMOD, to assess the effect of comorbidities on
      the labor force participation of 45-64-year-old Australians with heart disease,
      and the indirect economic costs to these individuals and government. For most
      comorbid conditions, there is a significant increase in the chance of an
      individual being out of the labor force, relative to those with heart disease
      alone. For example, individuals with heart disease and arthritis have more than 6
      fold the odds of being out of the labor force relative to those with heart
      disease alone (OR 6.64, 95% CI: 2.46-17.95). People with heart disease and >=1
      comorbidities also receive a significantly lower income, pay less in taxation and
      receive more in government transfer payments than those with heart disease alone.
      CONCLUSIONS:  It is important to consider whether an individual with heart
      disease also has other health conditions, as individuals with comorbidities have
      inferior financial situations and are a greater burden on government finances
      than those with only heart disease.  (Circ J 2014; 78: 644-648).

PMID- 24441576
TI  - In situ modulation of the vertical distribution in a blend of P3HT and PC(60)BM
      via the addition of a composition gradient inducer.
AB  - 2,2,3,3,4,4,4-Heptafluoro-N-phenyl-butyr-amide (F-ADD) was synthesized and shown
      to induce a composition gradient in a blend of P3HT and PC60BM. The addition of
      small amounts (ca. 0.5 wt%) of F-ADD modulated the chemical distribution in the
      blend along the vertical direction by controlling the blend component interface
      energy through selective interactions between F-ADD and PC60BM. A homogeneous
      compositional distribution along the vertical direction in the nanostructured
      bulk heterojunction (BHJ) increased the interfacial area, which shortened the
      exciton path length to the donor-acceptor interface and improved the photovoltaic
      performance. 

PMID- 24441577
TI  - Can a b value of 500 be substituted for a b value of 1000 in the characterization
      of focal liver lesions?
AB  - PURPOSE: Comparison of two different b values in diffusion-weighted magnetic
      resonance imaging (DWI) for characterization of focal liver lesions. METHODS: A
      total of 174 focal liver lesions from 100 patients were analyzed using two
      different b values (500 and 1000 s/mm(2)). The DWI with b values of 500 s/mm(2)
      (DWI500) and 1000 s/mm(2) (DWI1000) were analyzed using the Mann-Whitney test,
      kappa statistic, and paired t test with respect to image quality. The
      statistically significant differences between DWI500 and DWI1000 in the
      characterization of the lesions with respect to the cutoff ADC values were
      evaluated via chi (2) test. RESULTS: DWI500 had the highest mean score in the
      qualitative evaluation of image quality (p < 0.0001) and the highest signal-to
      noise ratio (8.7 +/- 2.1; p < 0.0001). The sensitivity, specificity, and AUC for
      discriminating malignant from benign focal lesions on DWI500 and DWI1000 using
      cutoff ADC values of 1.54 * 10(-3) and 1.38 * 10(-3) s/mm(2) were 95.8%, 92.3%,
      0.98, and 93.8%, 92.3%, 0.97, respectively. There was no statistically
      significant difference in sensitivity, specificity, and AUC values between DWI500
      and DWI1000 with respect to the cutoff ADC values (p > 0.05). CONCLUSIONS: The
      image quality of DWI500 was better than that of DWI1000, and there was no
      significant difference between DWI500 and DWI1000 in the characterization of the
      lesions with respect to the cutoff ADC values. The b value of 500 s/mm(2) can be
      substituted for the b value of 1000 s/mm(2) in the characterization of focal
      liver lesions.

PMID- 24441578
TI  - Pancreatic atrophy in patients with chronic graft-versus-host disease.
AB  - PURPOSE: To determine if patients with chronic graft-versus-host disease (cGVHD)
      following allogeneic hematopoietic stem cell transplantation (HSCT) develop
      greater loss of pancreatic tissue than patients without cGVHD. MATERIALS AND
      METHODS: This is an IRB-approved, HIPAA-compliant retrospective study of patients
      receiving allogeneic HSCT at our institution from 01/2006 to 01/2010 with
      abdominal CT performed within 3 months prior to HSCT and CT performed at least 3
      months after HSCT. Measurement of glandular tissue thickness of the head, body,
      and tail of the pancreas was performed independently by two radiologists blinded
      to clinical data. Statistical analysis was performed using the Student t-test,
      and interobserver agreement was evaluated with linear-weighted kappa. RESULTS:
      117 patients underwent HSCT during study period, with 36 patients meeting
      inclusion criteria. 22 subjects (61%) had clinical features of cGVHD, and 14
      patients (39%) did not have evidence of cGVHD. Following HSCT, there was a
      significant decrease in mean total thickness (10.9%, p = 0.002) of the pancreas
      in the group of patients with cGVHD. The change from pretreatment to the nadir in
      pancreatic thickness was significantly greater in patient with cGVHD (13.9 +/-
      12.1 mm), but not in non-cGVHD patients (5.4 +/- 4.7 mm) (p = 0.02), with head of
      the pancreas atrophy accounting for the difference (decrease of 4.8 +/- 4.6 mm in
      cGVHD patients vs. 1.6 +/- 2.1 mm in non-cGVHD patients (p = 0.02)). CONCLUSION:
      Patients with cGVHD develop significantly greater loss of pancreatic glandular
      tissue than patients without cGVHD following HSCT, with atrophy of pancreatic
      head being a major contributor.

PMID- 24441579
TI  - CT findings of gastric and intestinal anisakiasis.
AB  - PURPOSE: To illustrate the CT findings of gastrointestinal anisakiasis. SUBJECTS
      AND METHODS: The Institutional Review Board approving this retrospective study
      waived the requirement for informed consent. Review of our emergency department's
      clinical records from September 2008 to January 2012 identified 41 consecutive
      patients who were diagnosed with gastrointestinal anisakiasis. 20 patients were
      diagnosed with gastric anisakiasis with endoscopically proven Anisakis larvae,
      and 21 patients were diagnosed with intestinal anisakiasis with positive test
      results for anti-anisakidae antibody and the presence of intestinal lesions on
      CT. Two radiologists retrospectively assessed the CT findings. RESULTS: The mean
      time delay from raw fish ingestion to symptom onset was 5.2 h (range 0.5-24 h) in
      gastric anisakiasis and 39 h (range 12-120 h) in intestinal anisakiasis. Gastric
      anisakiasis showed marked submucosal edema of the gastric wall (20/20 patients,
      100%), increased attenuation of adjacent fat (19/20, 95%), and ascites (14/20,
      70%) on CT. Intestinal anisakiasis showed marked submucosal edema of the
      intestine (21/21 patients, 100%) without showing complete intraluminal occlusion,
      ascites (21/21, 100%), increased attenuation of adjacent fat (19/21, 90%), and
      fluid collection in the distal segment of the constricted small intestine (13/21,
      62%) on CT. CONCLUSION: Severe submucosal edema with ascites is a characteristic
      finding of gastrointestinal anisakiasis when compared with other forms of
      gastroenteritis. When CT shows the typical findings of gastrointestinal
      anisakiasis, radiologists may suggest the possibility of clinically undiagnosed
      anisakiasis, especially in intestinal anisakiasis as the diagnosis is sometimes
      difficult due to the long interval between food intake and symptom onset.

PMID- 24441580
TI  - Venous filling defects on portal venous phase CT of the abdomen and pelvis:
      clinical implications and positive predictive value for diagnosing deep venous
      thrombosis.
AB  - PURPOSE: To determine the prevalence, resulting clinical decisions, and the
      positive predictive value (PPV) of venous filling defects detected on portal
      venous phase (PVP) CT. METHODS: Over a 3-year period, 42412 consecutive patients
      underwent a PVP abdominopelvic CT; of these, 348 reports mentioned a filling
      defect concerning for deep venous thrombosis (DVT) in the IVC, iliac, or common
      femoral veins. Ninety-three patients underwent a reference standard venous
      imaging study. RESULTS: The prevalence of venous filling defects in CT reports
      was 0.82% (n = 348). Reports worded with higher degrees of certainty were
      statistically more likely to result in treatment, while lower certainty was
      correlated with additional confirmatory imaging. The PPV for detection of DVT was
      77%. The presence of peri-vascular stranding or vessel expansion increased the
      PPV of PVP CT to 95% and 100%, respectively. CONCLUSION: While the PPV for
      filling defects on PVP CT was modest, it was substantially improved if peri
      venous stranding or vessel expansion was present.

PMID- 24441581
TI  - Fertility Preservation Decisions Among Newly Diagnosed Oncology Patients: A
      Single-Center Experience.
AB  - OBJECTIVES: To evaluate fertility preservation decisions and compare controlled
      ovarian stimulation (COS) and assisted reproductive technology (ART) outcomes
      between newly diagnosed cancer patients and age-matched healthy controls.
      METHODS: Our retrospective study was conducted at Columbia University's Center
      for Women's Reproductive Care between 2005 and 2012. Forty-nine women elected to
      undergo ART with COS for either oocyte or embryo cryopreservation before
      commencement of cancer therapy. Demographic and descriptive characteristics were
      collected from the cohort of patients. Treatment outcomes were compared with
      randomly selected, healthy, age-matched controls undergoing ART with COS during
      the same time period. RESULTS: Single women began fertility preservation cycles
      in half the time of married women (10.4 vs. 22.9 d). All 21 married women chose
      embryo cryopreservation, whereas 17 of the 28 (61%) single women chose embryo
      over oocyte cryopreservation. Baseline anti-Mullerian hormone levels and body
      mass indices were similar among fertility preservation patients and controls.
      Despite elevated baseline estradiol (E2) levels and luteal phase cycle starts in
      some cycles to avoid delay of cancer treatment, no significant differences were
      noted when comparing days of stimulation, total gonadotropins prescribed, numbers
      of oocytes and mature oocytes retrieved, fertilization rate, or cancellation rate
      to controls. CONCLUSIONS: Our experience shows that, with appropriate counseling
      and multidisciplinary care, newly diagnosed cancer patients desiring fertility
      preservation experience similar outcomes as age-matched healthy controls. These
      women can pursue oocyte or embryo cryopreservation with likely minimal disruption
      to the flow of their oncologic care.

PMID- 24441582
TI  - Dose-Escalation Study of Thoracic Radiotherapy in Combination With Pemetrexed
      Plus Cisplatin in Japanese Patients With Locally Advanced Nonsquamous Non-Small
      Cell Lung Cancer: A Post Hoc Analysis of Survival and Recurrent Sites.
AB  - OBJECTIVES: We performed a post hoc analysis of progression-free survival (PFS),
      overall survival (OS), and recurrent sites in patients with locally advanced
      nonsquamous non-small cell lung cancer who were enrolled in a phase I trial of
      combination chemotherapy consisting of pemetrexed plus cisplatin with concurrent
      thoracic radiotherapy. METHODS: Patients received pemetrexed (500 mg/m2) plus
      cisplatin (75 mg/m2) on day 1 every 3 weeks for 3 cycles plus concurrent thoracic
      radiotherapy consisting of 60 Gy (n=6) or 66 Gy (n=12); 4 to 6 weeks thereafter,
      patients received consolidation treatment with pemetrexed (500 mg/m) every 3
      weeks for up to 3 cycles. We reviewed the medial records to collect data on
      progression, recurrent sites, late toxicity, and survival. RESULTS: No late
      radiation morbidity was observed. Thirteen patients (72%) exhibited disease
      progression: 8 patients had distant metastases, 8 patients had local recurrence
      (within the radiation field [n=6], outside the radiation field [n=2], and both
      [n=1]), and 3 patients had local recurrence plus distant metastases. The median
      PFS was 10.5 months (95% confidence interval [CI], 8.8-12.3), and the 3-year PFS
      rate was 28% (95% CI, 7.0-48.6). Ten of the 18 patients died of lung cancer. The
      median follow-up time for the censored cases was 42.8 months (range, 38.1 to 52.9
      mo). The median OS was 27.3 months (95% CI, 13.1-41.6), and the 3-year OS rate
      was 50% (95% CI, 26.9-73.1). CONCLUSIONS: The median PFS and OS in our study were
      comparable to those of historical chemoradiotherapy controls.

PMID- 24441583
TI  - Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma:
      Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron
      Emission Tomography.
AB  - OBJECTIVES: To report outcomes after yttrium-90 microsphere brachytherapy for
      unresectable liver metastases from uveal melanoma and to evaluate factors
      predictive for overall survival (OS) and hepatic progression-free survival (PFS).
      METHODS: A total of 71 patients were consecutively treated with microsphere
      brachytherapy for unresectable liver metastases from uveal melanoma between 2007
      and 2012. Clinical, radiographic, and positron emission tomography-derived,
      functional tumor parameters were evaluated by log-rank test in univariate
      analysis and backwards stepwise multivariate Cox proportional hazards regression.
      OS and hepatic PFS were estimated by Kaplan-Meier analysis. RESULTS: A total of
      134 procedures were performed in 71 patients with a median age of 63 years
      (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere
      brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere
      brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9
      to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases
      was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex,
      pretreatment metabolic tumor volume, and total glycolic activity (TGA) were
      significantly correlated with hepatic PFS and OS. In multivariate analysis,
      female sex and TGA retained significance as independent predictors of hepatic PFS
      and OS. A low pretreatment TGA (<225 g) was associated with a significantly
      longer median OS than was a TGA>=225 g (17.2 vs. 9.7 mo, P=0.01). CONCLUSIONS:
      Yttrium-90 microsphere brachytherapy provided favorable survival times in
      patients with unresectable liver metastases from uveal melanoma. Metabolic tumor
      volume and TGA are predictive functional tumor parameters, which may aid patient
      selection and risk stratification.

PMID- 24441584
TI  - Long-term Outcomes Following Radiation Therapy For Prostate Cancer Patients With
      Lymph Node Metastases at Diagnosis Treated With and Without Surgery.
AB  - OBJECTIVES: To evaluate the long-term outcomes for prostate cancer (PCa) patients
      with lymph node involvement (LNI) treated with radiotherapy at the University of
      California San Francisco. MATERIALS AND METHODS: All newly diagnosed PCa patients
      with LNI treated with radiotherapy as primary therapy or after surgery, each with
      and without hormonal therapy (HT) between 1988 and 2009 were included.Thirty-five
      patients (38%) were managed with external beam radiotherapy alone (eRT), 18
      patients (20%) with radical prostatectomy (RP)+adjuvant radiotherapy, and 38
      patients (42%) with RP+salvage radiotherapy. Overall 82% of the study sample
      received HT with similar proportions among radiation therapy (RT) subsets
      (P=0.83). RESULTS: The median follow-up (FU) was 65, 42, and 86 months for
      patients treated with eRT, adjuvant radiotherapy, and salvage radiotherapy,
      respectively.The 10-year estimates from start of primary therapy for patients
      with LNI for overall survival (OS) was 78% (95% confidence interval [CI], 62%
      88%) and for cause-specific survival was 89% (95% CI, 78%-95%). The 5-year
      estimates from the start of RT for biochemically no evidence of disease was 68%
      (95% CI, 56%-78%) and for disease-free survival was 67% (95% CI, 54%-77%). There
      was no difference in any of these outcomes among the 3 RT groups.Patients treated
      with HT were more likely to have a better 10-year OS (82% vs. 66%; log rank:
      P=0.001).Multivariate analysis indicated that only age and Gleason score were
      significant predictors for biochemically no evidence of disease and OS.
      CONCLUSIONS: Patients diagnosed with PCa with LNI who were treated with RT with
      or without a prior surgery had relatively favorable long-term outcomes.

PMID- 24441585
TI  - Automated method for determining the flow of surface functionalized nanoparticles
      through a hydraulically fractured mineral formation using plasmonic silver
      nanoparticles.
AB  - Quantifying nanoparticle (NP) transport within porous geological media is
      imperative in the design of tracers and sensors to monitor the environmental
      impact of hydraulic fracturing that has seen increasing concern over recent
      years, in particular the potential pollution and contamination of aquifers. The
      surface chemistry of a NP defining many of its solubility and transport
      properties means that there is a wide range of functionality that it is desirable
      to screen for optimum transport. Most prior transport methods are limited in
      determining if significant adsorption occurs of a NP over a limited column
      distance, however, translating this to effects over large distances is difficult.
      Herein we report an automated method that allows for the simulation of adsorption
      effects of a dilute nanoparticle solution over large distances under a range of
      solution parameters. Using plasmonic silver NPs and UV-visible spectroscopic
      detection allows for low concentrations to be used while offering greater
      consistency in peak absorbance leading to a higher degree of data reliability and
      statistics. As an example, breakthrough curves were determined for
      mercaptosuccinic acid (MSA) and cysteamine (CYS) functionalized Ag NPs passing
      through Ottawa sand (typical proppant material) immobile phase (C) or bypassing
      the immobile phase (C0). Automation allows for multiple sequences such that the
      absorption plateau after each breakthrough and the rate of breakthrough can be
      compared for multiple runs to provide statistical analysis. The mobility of the
      NPs as a function of pH is readily determined. The stickiness (alpha) of the NP
      to the immobile phase calculated from the C/C0 ratio shows that MSA-Ag NPs show
      good mobility, with a slight decrease around neutral pH, while CYS-Ag NPs shows
      an almost sinusoidal variation. The automated process described herein allows for
      rapid screening of NP functionality, as a function of immobile phase (proppant
      versus reservoir material), hydraulic fracturing fluid additives (guar,
      surfactant) and conditions (pH, temperature). 

PMID- 24441586
TI  - Integrated RAS signaling defined by parallel NMR detection of effectors and
      regulators.
AB  - The RAS GTPase directs cell proliferation and survival by selectively relaying
      signals amid a dynamic network of regulatory enzymes and protein interactions.
      Oncogenic mutation of RAS alters cell growth by deleteriously controlling output
      to RAS-binding effectors. Mechanisms underlying multieffector interactions for
      both wild-type and oncogenic RAS are poorly understood owing to challenges in
      quantifying outputs to multiple pathways in parallel. Using highly selective NMR
      probes for wild-type and oncogenic (G12V) RAS, we develop a systematic approach
      that quantitatively measures RAS output in composite mixtures of GEF, GAP and
      effector RAS-binding domains (RBDs). We derive effector signaling hierarchies and
      establish how oscillating concentrations generate effector 'switching'. The G12V
      mutation highly perturbs this system, specifically altering interactions with RAL
      GTPase-specific GEFs and RAF kinases. We further reveal that RAS-RBD complexes
      show extensive feedback to full-length regulatory proteins. Our approach
      quantifies output from signaling hubs, here providing an integrated view of the
      RAS network. 

PMID- 24441588
TI  - Insights into the phosphatase and the synthase activities of human
      bisphosphoglycerate mutase: a quantum mechanics/molecular mechanics simulation.
AB  - Bisphosphoglycerate mutase (BPGM) is a multi-activity enzyme. Its main function
      is to synthesize the 2,3-bisphosphoglycerate, the allosteric effector of
      hemoglobin. This enzyme can also catalyze the 2,3-bisphosphoglycerate to the 3
      phosphoglycerate. In this study, the reaction mechanisms of both the phosphatase
      and the synthase activities of human bisphosphoglycerate mutase were
      theoretically calculated by using the quantum mechanics/molecular mechanics
      method based on the metadynamics and umbrella sampling simulations. The
      simulation results not only show the free energy curve of the phosphatase and the
      synthase reactions, but also reveal the important role of some residues in the
      active site. Additionally, the energy barriers of the two reactions indicate that
      the activity of the synthase in human bisphosphoglycerate mutase is much higher
      than that of the phosphatase. The estimated reaction barriers are consistent with
      the experimental data. Therefore, our work can give important information to
      understand the catalytic mechanism of the bisphosphoglycerate mutase family. 

PMID- 24441587
TI  - Allostery in Ca2+ channel modulation by calcium-binding proteins.
AB  - Distinguishing between allostery and competition among modulating ligands is
      challenging for large target molecules. Out of practical necessity, inferences
      are often drawn from in vitro assays on target fragments, but such inferences may
      belie actual mechanisms. One key example of such ambiguity concerns calcium
      binding proteins (CaBPs) that tune signaling molecules regulated by calmodulin
      (CaM). As CaBPs resemble CaM, CaBPs are believed to competitively replace CaM on
      targets. Yet, brain CaM expression far surpasses that of CaBPs, raising questions
      as to whether CaBPs can exert appreciable biological actions. Here, we devise a
      live-cell, holomolecule approach that reveals an allosteric mechanism for calcium
      channels whose CaM-mediated inactivation is eliminated by CaBP4. Our strategy is
      to covalently link CaM and/or CaBP to holochannels, enabling live-cell
      fluorescence resonance energy transfer assays to resolve a cyclical allosteric
      binding scheme for CaM and CaBP4 to channels, thus explaining how trace CaBPs
      prevail. This approach may apply generally for discerning allostery in live
      cells. 

PMID- 24441589
TI  - Biomechanical testing of a hybrid locking plate fixation of equine sesamoid
      osteotomies.
AB  - OBJECTIVE: To compare the biomechanical properties of a hybrid locking
      compression plate (LCP) construct with the compression screw technique as a
      treatment for transverse mid-body proximal sesamoid bone fractures. METHODS: Ten
      paired forelimbs from abattoir horses were used. The medial proximal sesamoid
      bone of each limb was osteotomized transversely and randomly assigned, to either
      repair with a two-hole 3.5 mm LCP or a 4.5 mm cortical screw placed in lag
      fashion. Each limb was tested biomechanically by axial loading in single cycle
      until failure. The point of failure was evaluated from the load-displacement
      curves. Then a gross evaluation and radiographs were performed to identify the
      mode of failure. RESULTS: The loads to failure of limbs repaired with the hybrid
      LCP construct (4968 N +/- 2167) and the limbs repaired with the screw technique
      (3009 N +/- 1091) were significantly different (p <0.01). The most common mode of
      failure was through a comminuted fracture of the apical fragment of the proximal
      sesamoid bone. CLINICAL SIGNIFICANCE: The LCP technique has potential to achieve
      a better fracture stability and healing when applied to mid-body fractures of the
      proximal sesamoid bone. Further testing, particularly fatigue resistance is
      required to corroborate its potential as a treatment option for mid-body
      fractures of the proximal sesamoid bone.

PMID- 24441590
TI  - [Evaluation of drug information service available for physicians regarding low
      dose aspirin-induced gastrointestinal lesions].
AB  - Low-dose aspirin-induced gastrointestinal lesions are becoming an important
      problem in clinical practice. In our investigation of such adverse effects, we
      obtained 4 important findings considered useful for physicians, as follows; 1)
      even when aspirin was given at a dose, the incidence rate of gastrointestinal
      lesions was higher than with other non-steroidal anti-inflammatory drugs
      (NSAIDs), 2) the odds ratios for gastrointestinal lesions induced by aspirin with
      a histamine H2 receptor antagonist and proton pump inhibitor were 0.6 and 0.4,
      respectively, as compared with aspirin alone, 3) it is difficult to administer
      aspirin, which exerts an antiplatelet effect, without inducing gastrointestinal
      lesions, and 4) these gastrointestinal lesions appears early, especially within 2
      years after administration. We distributed a questionnaire to 41 physicians to
      confirm our findings, and compared high (n=20) and low (n=21) frequency aspirin
      prescription groups. The recognition rate of points 1 and 3 noted above in the
      high group was significantly elevated as compared to the low group, whereas there
      no significant difference in regard to the information in point 4 between the
      groups and the rate of recognition was low. Moreover, only 27% of the surveyed
      physicians were familiar with all 4 points. Prior to receiving this information,
      17% of the physicians gave no related instructions their patients, which was
      reduced to 0% after receiving this information. Furthermore, 98% of those
      surveyed found the information to be useful. Our results suggest that these 4
      points of information regarding potential adverse gastrointestinal effects of low
      dose aspirin are useful for physicians.

PMID- 24441591
TI  - Non-invasive detection of infection in acute pancreatic and acute necrotic
      collections with diffusion-weighted magnetic resonance imaging: preliminary
      findings.
AB  - PURPOSE: The purpose of this study was to evaluate the contribution of diffusion
      weighted magnetic resonance imaging (DW-MRI) to the detection of infection in
      acute pancreatitis-related collections. METHODS: A total of 21 DW-MRI, and
      computed tomography (CT) were performed on 20 patients diagnosed as acute
      pancreatitis with acute peri-pancreatic fluid or necrotic collections.
      Collections were classified as infected or sterile according to the culture and
      follow-up results. Collections with gas bubbles on CT images were considered to
      be infected. Collections with peripheral bright signals on DW-MRI images were
      considered to be positive, whereas those without signals were considered to be
      negative. Apparent diffusion coefficient (ADC) values of the peripheral and
      central parts of the collections were measured. Student's t test was used to
      compare the means of ADC values of independent groups. RESULTS: Apart from one
      false positive result, the presence of infection was detected by DW-MRI with
      95.2% accuracy. The sensitivity and accuracy of DW-MRI were higher than CT for
      the detection of infection. The ADC values in the central parts of the
      collections were significantly different between the infected and sterile groups.
      CONCLUSION: DW-MRI can be used as a non-invasive technique for the detection of
      infection in acute pancreatitis-associated collections.

PMID- 24441593
TI  - A comparative study of supercapacitive performances of nickel cobalt layered
      double hydroxides coated on ZnO nanostructured arrays on textile fibre as
      electrodes for wearable energy storage devices.
AB  - We demonstrated an efficient method for the fabrication of novel, flexible
      electrodes based on ZnO nanoflakes and nickel-cobalt layered double hydroxides
      (denoted as ZnONF/NiCoLDH) as a core-shell nanostructure on textile substrates
      for wearable energy storage devices. NiCoLDH coated ZnO nanowire (denoted as
      ZnONW/NiCoLDH) flexible electrodes are also prepared for comparison. As an
      electrode for supercapacitors, ZnONF/NiCoLDH exhibits a high specific capacitance
      of 1624 F g(-1), which is nearly 1.6 times greater than ZnONW/NiCoLDH
      counterparts. It also shows a maximum energy density of 48.32 W h kg(-1) at a
      power density of 27.53 kW kg(-1), and an excellent cycling stability with
      capacitance retention of 94% and a Coulombic efficiency of 93% over 2000 cycles.
      We believe that the superior performance of the ZnONF/NiCoLDH hybrids is due
      primarily to the large surface area of the nanoflake structure and the open
      spaces between nanoflakes, both of which provide a large space for the deposition
      of NiCoLDH, resulting in reduced internal resistance and improved capacitance
      performance. Our results are significant for the development of electrode
      materials for high-performance wearable energy storage devices. 

PMID- 24441592
TI  - A qualitative study of smokers' responses to messages discouraging dual tobacco
      product use.
AB  - Cigarette companies increasingly promote novel smokeless tobacco products to
      smokers, encouraging them to use smokeless tobacco in smoke-free environments.
      New messages may counteract this promotion. We developed 12 initial anti
      smokeless message ideas and tested them in eight online focus groups with 75 US
      smokers. Those smokers who never tried smokeless tobacco were unaware of health
      risks of novel smokeless tobacco products, perceived scary messages as effective
      and acknowledged the addictive nature of nicotine. Smokers who had tried
      smokeless tobacco shared their personal (mainly negative) experiences with
      smokeless tobacco, were aware of health risks of novel smokeless tobacco
      products, but denied personal addiction, and misinterpreted or disregarded more
      threatening messages. Portraying women as smokeless tobacco users was perceived
      as unbelievable, and emphasizing the lack of appeal of novel smokeless tobacco
      products was perceived as encouraging continued smoking. Future ads should
      educate smokers about risks of novel smokeless tobacco products, but past users
      and never users may require different message strategies. 

PMID- 24441594
TI  - Design of algal film photobioreactors: material surface energy effects on algal
      film productivity, colonization and lipid content.
AB  - A parallel plate air lift reactor was used to examine the growth kinetics of
      mixed culture algal biofilms grown on various materials (acrylic, glass,
      polycarbonate, polystyrene and cellulose acetate). The growth kinetics of the
      algal biofilms were non-linear overall and their overall productivities ranged
      from 1.10-2.08g/m(2)day, with those grown on cellulose acetate having the highest
      productivity. Overall algal biofilm productivity was largely explained by
      differences in the colonization time which in turn was strongly correlated to the
      polar surface energy of the material, but weakly correlated to water-material
      contact angle. When colonization time was taken into account, the productivity
      for all materials except acrylic was not significantly different at approximately
      2g/m(2)/day. Lipid content of the algal biofilms ranged from 6% to 8% (w/w) and
      was not correlated to water-material contact angle or polar surface energy. The
      results have potential application for selecting appropriate materials for algal
      film photobioreactors. 

PMID- 24441595
TI  - The metal-insulator transition in trivalent-ion-doped tungsten bronzes.
AB  - Electrical transport measurements have been made on a series of trivalent-ion
      doped tungsten bronzes MxWO3, with M = Y (0.05 <= x <= 0.12) or La (0.05 <= x <=
      0.19), over the temperature range 2-300 K. The results are consistent with a
      metal-insulator transition (MIT) at a critical concentration xC ? 0.06, which
      corresponds to an electron concentration nC ? 3.3 * 10(21) cm(-3). The appearance
      of small concentrations of non-cubic phases for x ~ xC does not have a
      significant impact on the evolution of the electronic properties of the trivalent
      bronzes in the low x range. Analysis of the transport results, and a comparison
      of the findings with those obtained by other workers for the sodium tungsten
      bronzes, suggest that electron-electron interaction effects play a significant
      role in inducing the MIT in this type of disordered system.

PMID- 24441596
TI  - From the guest editor.

PMID- 24441597
TI  - Occupational health and safety and the functions of law: a system's analysis.
AB  - The article suggests a model that can account for the systemic nature of the
      law's functions with regard to occupational health and safety. The model presents
      four functions for law's intervention: to establish standards, to ensure the
      welfare of those injured on the job, to provide incentives for employers and
      employees to reduce the level of injuries, and to ensure the efficient
      administration of public expenditures. The model requires observing law's
      intertwining functions in context and assessing the output according to a
      weighted index. The article applies this framework for a critical description of
      the Israeli system. While injury rates in Israel are 'normal', compared to other
      industrialized countries, the findings suggest some deficiencies in the functions
      of law including: inadequate adaptation of the standardization process to the
      challenges of the 'new workplace', incomplete incentives for adopting a high
      level of care and for compliance with standards, a relative failure of effort to
      induce a managerial culture that cooperates with workers on issues of health and
      safety, and a general fragmentation of the system. 

PMID- 24441598
TI  - Prevalence and risk factors of upper extremity cumulative trauma disorder in
      dental hygienists.
AB  - Cumulative trauma disorder (CTD) refers to a number of conditions arising from
      overuse of joints or soft tissues. The common risk factors that contribute to the
      development of these disorders are related to personal and occupational
      variables. Job analysis of the tasks performed by the dental hygienist have shown
      that this occupation is particularly at risk. The objectives of this study were
      to determine the prevalence of CTD symptoms amongst dental hygienists in Israel
      and to identify which are the factors that are related to CTD. A questionnaire
      including items concerning demographic data, employment history, professional
      occupational information, use of instrumentation, and CTD symptomatology was
      mailed to all 530 registered dental hygienists. Two hundred forty-six hygienists
      (46%) returned the questionnaire; 63% of the respondents were classified as CTD
      'sufferers', Age, year of graduation, hours worked per week, and frequency of
      changing instruments were found to be significantly related to CTD symptoms.
      Hygienists at high risk included those aged 50 years or more (Odds ratio, OR =
      6), those who graduated before 1986 (OR = 3), those who work more than 34 h per
      week (OR = 2.5) and those who change two or fewer instruments per patient (OR =
      2). The major recommendation resulting from this study is to make dental
      hygienists aware that they work in a high-risk profession. It is hoped that
      increased awareness of the risk will spur the hygienist to make appropriate work
      practice, administrative, and engineering modifications and to seek treatment at
      the first indication of CTD symptoms. 

PMID- 24441599
TI  - Virtual reality applications to work.
AB  - Virtual reality (VR) entails the use of advanced technologies, including
      computers and various multimedia peripherals, to produce a simulated (i.e.
      virtual) environment that users perceive as comparable to real world objects and
      events. With the aid of specially designed transducers and sensors, users
      interact with displayed images, moving and manipulating virtual objects, and
      performing other actions in a way that engenders a feeling of actual presence
      (immersion) in the simulated environment. The unique features and flexibility of
      VR give it extraordinary potential for use in work-related applications. It
      permits users to experience and interact with a life-like model or environment,
      in safety and at convenient times, while providing a degree of control over the
      simulation that is usually not possible in the real-life situation. The work
      related applications that appear to be most promising are those that employ
      virtual reality for visualization and representation, distance communication and
      education, hands-on training, and orientation and navigation. This article
      presents an overview to the concepts of VR focusing on its applications in a
      variety of work settings. Issues related to potential difficulties in using VR
      including side effects and the transfer of skills learned in the virtual
      environment to the real world are also reviewed. 

PMID- 24441600
TI  - Ergonomic factors influencing handwriting performance.
AB  - OBJECTIVES: Handwriting is one of the first things children are taught at school
      and need to perform in an efficient manner throughout life. Various studies have
      indicated that handwriting skills are related to many different variables
      including ergonomic factors. The purpose of this study was to investigate the
      differences between children with good and poor handwriting on ergonomic factors
      that underlie handwriting (e.g. body and paper positioning, pencil-grip and
      pressure) and to examine the relationship between the handwriting legibility and
      speed and these ergonomic factors. STUDY DESIGN: The study included 209 students
      in Grades 2 and 3 in Israel. The students were identified as good (N=116) and as
      poor handwriters (N=103) by their teachers. The Hebrew Handwriting Evaluation
      (HHE) was used to collect data on handwriting quality and speed as well as on
      ergonomic factors. A Chi square procedure was used to compare the differences
      between the handwriting groups. Discriminant analysis determined the percent of
      correct discrimination of subjects with poor or good handwriting based on the
      ergonomic factors. Finally, Spearman correlation coefficients were employed
      between the ergonomic variables and speed and quality of handwriting. RESULTS:
      The results indicated that children with poor handwriting had inferior pencil,
      paper and body positioning, stabilization of paper and consistency of pressure,
      compared to children with good handwriting. CONCLUSIONS: The implications of the
      results in general, and specifically for clinical practice are discussed.
      Finally, further research related to this topic is suggested.

PMID- 24441601
TI  - Does fatigue influence children's handwriting performance?
AB  - OBJECTIVES: Handwriting is one aspect of school children's work. This article
      examines the influence of fatigue on handwriting, through the use of prolonged
      writing. STUDY DESIGN: The study population included 157 third-grade students
      with good and poor handwriting. Quality and speed of handwriting, in addition to
      ergonomic factors, were assessed through the Hebrew Handwriting Evaluation (HHE),
      prior to writing and after writing for 10 consecutive minutes. RESULTS: RESULTS
      of this study clearly demonstrate that children with both poor and good
      handwriting perform more poorly after writing long texts. Although both groups
      were influenced by the fatigue situation, poor handwriters still scored lower
      than the good handwriters in both conditions (fatigue and non-fatigue), on most
      variables. CONCLUSIONS: Continued studies in this area are recommended, and it is
      suggested that children take 'writing breaks' when writing, in order to improve
      the quality of their handwriting.

PMID- 24441602
TI  - Validity of the Purdue Pegboard Test in assessing patients after traumatic hand
      injury.
AB  - OBJECTIVES: The purposes of this study were first, to determine the validity of
      the Purdue Pegboard Test in differentiating between groups of healthy adults and
      adults who suffered from traumatic hand injury. Second, to determine criterion
      validity of the Purdue Pegboard Test with the Functional Dexterity Test (FDT).
      Third, to test the correlations between the Purdue Pegboard Test and several
      functional hand activities. STUDY DESIGNS: Fifty-four post-traumatic hand injury
      participants who were treated in the Occupational Therapy Clinic at the Sheba
      Medical Center, Tel Hashomer, Israel. Forty-three healthy participants with no
      history of hand injury or disease formed the control group. All subjects were
      assessed with the Purdue Pegboard Test, PDT and five functional hand activities.
      RESULTS AND CONCLUSIONS: The Purdue Pegboard Test differentiated between the
      healthy population and the post-traumatic hand injury population. No significant
      differences were found between the dominant hand-injured group and the non
      dominant hand-injured group on three scores (both hands, assembly and the
      summarizing of the first three sub-tests). Correlations between the Purdue
      Pegboard Test and the PDT were moderate to high suggesting the two tests should
      be used in combination when assessing patients. Correlations between the Purdue
      and hand activities (e.g. button, laces) were moderate. Further studies are
      needed to examine the relationships between types of hand injuries, ROM, pinch
      grip and performance on the Purdue Pegboard Test.

PMID- 24441603
TI  - Do worker's chronically exposed to lead have leukocytosis?
AB  - In the following study, we examined the possible relationship between acute and
      chronic measures of lead exposure and total white cell blood counts in 94 workers
      in a lead-battery plant who were followed-up from 1980 to 1993. Acute measures of
      lead exposure included blood lead (PbB), and zinc protoporphyrin levels (ZPP)
      measured concomitantly with the total white blood count, and a measure of chronic
      exposure was represented by average blood lead levels over the follow-up period.
      Of the 947 white blood cell counts, leukocytosis was found in 92 (9.7%), but
      there was no higher proportion of leukocytosis in the groups with higher PbB or
      ZPP results. Of those where a smoking history was recorded, none of the 188 non
      smokers had leukocytosis, compared to 78 of 590 smokers (0 vs. 13.2%,
      respectively, P < 0.05). The white count was not significantly correlated with
      ZPP, PbB or the average PbB of the workers. We conclude that lead exposure does
      not influence the white blood cell count in battery workers, and that the cause
      of an elevated white count in such worker's is probably due entirely to a history
      of smoking. Further studies are warranted to substantiate our findings. 

PMID- 24441604
TI  - The effect of exposure to SO2 on the respiratory system of power-station workers.
AB  - Sulfur dioxide (SO2) is generally recognized as a respiratory irritant, but its
      effects if any at low levels of exposure are uncertain. We studied 38 power
      station technicians exposed to 0.8 ppm (parts per million) 8-h weighted levels of
      sulfur dioxide, and compared them to workers performing similar tasks without
      such exposure. Those exposed complained 5.8 times more frequently of cough (95%
      CI =1.8-20.6, P < 0.001), and also had significantly more sputum production.
      There was also a trend for increasing prevalence of dyspnea. On the other hand
      there was no decrease in pulmonary function test values. In the eight exposed
      subjects who complained of dyspnea, there was a significant decrease in pulmonary
      flow values. We conclude that power station workers exposed to low levels of SO2
      have increased respiratory symptoms, and deserve compensation if their symptoms
      become chronic. The pulmonary function tests were not different from the control
      subjects, but there may be a small group who are prone to long-term morbidity.
      Additional studies are warranted to confirm our findings, and to define immediate
      and long-term morbidity due to low exposure to SO2. 

PMID- 24441605
TI  - Using career choice considerations in the counseling process: examination of the
      structure of preferences, gender and age differences.
AB  - The aim of this research was to examine the structure of career choice
      considerations and to outline group differences in these considerations.
      Following the aspect-based approach to career decision making, a considerations
      questionnaire was established and given to 754 young adults who applied to the
      Hadassah Career Counseling Institute. Holland's self-directed search
      questionnaires were also given. Seven core factors which underline people's
      considerations were derived and compared to Holland's interest types. Gender and
      age differences in the importance assigned to career considerations were also
      examined and analyzed via the seven core factors. The results show both the
      common and distinctive features of the considerations structure and the interest
      structure. Several significant group differences in career considerations were
      established. Ways to incorporate the findings in occupational counseling are
      discussed and the contribution of a systematized considerations questionnaire is
      outlined. 

PMID- 24441606
TI  - Older people's driving habits, visual abilities, and subjective assessment of
      daily visual functioning.
AB  - OBJECTIVES: To explore the relationship between the status of daily visual
      functions, as measured by Mangione et al.'s (1992) ADVS, and: (a) visual
      functions that are related to driving; (b) the tendency of elderly people to
      drive in different visual conditions; and (c) the reasons older people give for
      limiting their driving under different conditions. STUDY DESIGN: The subjects
      were 80 elderly people, ages 64-85. Seventy three of these people still drove and
      seven had quit driving. Each participant was individually administered (a) a
      subjective questionnaire containing the ADVS and questions from the Established
      Populations for the Epidemiological Studies of the Elderly (EPESE); (b) objective
      measures of visual performance including visual acuity, contrast sensitivity, and
      visual search speed. RESULTS: Strong correlations were obtained between the
      responses to the subjective questionnaire and the objective measures of visual
      skills. Most subjects were cognizant of the changes in their quality of vision
      and changed their driving habits accordingly by avoiding driving at dark, on
      unfamiliar roads, and on long trips. There were also significant associations
      between the changes in driving behavior and performance on the vision tests.
      CONCLUSION: The ADVS can be used as a self-administered test of driving-related
      visual functioning, and is most relevant to self-restrictions in night driving.

PMID- 24441607
TI  - Dynamic cognitive therapy according to Feuerstein in learning and adaptation
      difficulties.
AB  - This article is a case study describing the treatment of a 23-year-old man with
      learning and adaptational difficulties who was unable to find his professional
      vocational niche. The treatment is a combination between the Feuerstein's
      approach and his tools with Toglia's problem solving model. 

PMID- 24441608
TI  - Reported level of pain of upper extremities related to multi-factorial workloads
      among office workers during and after work hours.
AB  - OBJECTIVES: This research compared the level of reported pain between women
      workers with high workload (main work involved typing) and women workers with low
      workload (various office work where typing was not the main task). The research
      examined the relationship between reported pain of upper extremities (UE) and the
      following variables: physical strain exerted during typing on a computer
      keyboard, extra-work strain on UE, bio-demographic variables, psychosocial
      variables, and ergonomic variables. STUDY DESIGN: Participants were 60 women who
      worked in offices, divided into two groups. The index group included women whose
      main work involved typing (high workload: M=6.16 h of typing per day), and the
      control group did various office work where typing was not the main task (low
      workload: M=3.23 h of typing per day). The level of pain, physical strain, and
      data concerning bio-demographic variables, psychosocial variables and ergonomic
      variables was assessed by a self-reported questionnaire. RESULTS: The results
      suggested that there was a significant difference between workers with high and
      low typing workloads. Workers with higher typing load reported higher levels of
      pain. There was a significant positive correlation between level of reports of
      pain and levels of physical overload at work, and extra-work strain on UE both
      among workers with high and low workloads. It was also found that levels of pain
      correlated significantly with bio-demographic variables (age and number of
      children) and psychosocial variables (managerial responsibilities) among low
      workload workers only. CONCLUSIONS: The research on pain of UE indicates that
      pain may be affected by a multi-factorial nature of a work-related environment
      which includes physical strain exerted during typing on a computer keyboard,
      extra-work strain on UE, bio-demographic variables and psychosocial variables.

PMID- 24441611
TI  - Volume contentsVolume 11 (1998).

PMID- 24441609
TI  - Author indexVolume 11 (1998).

PMID- 24441615
TI  - From the editor.

PMID- 24441613
TI  - The marine fungal metabolite, AD0157, inhibits angiogenesis by targeting the Akt
      signaling pathway.
AB  - In the course of a screening program for the inhibitors of angiogenesis from
      marine sources, AD0157, a pyrrolidinedione fungal metabolite, was selected for
      its angiosupressive properties. AD0157 inhibited the growth of endothelial and
      tumor cells in culture in the micromolar range. Our results show that subtoxic
      doses of this compound inhibit certain functions of endothelial cells, namely,
      differentiation, migration and proteolytic capability. Inhibition of the
      mentioned essential steps of in vitro angiogenesis is in agreement with the
      observed antiangiogenic activity, substantiated by using two in vivo angiogenesis
      models, the chorioallantoic membrane and the zebrafish embryo neovascularization
      assays, and by the ex vivo mouse aortic ring assay. Our data indicate that AD0157
      induces apoptosis in endothelial cells through chromatin condensation, DNA
      fragmentation, increases in the subG1 peak and caspase activation. The data shown
      here altogether indicate for the first time that AD0157 displays antiangiogenic
      effects, both in vitro and in vivo, that are exerted partly by targeting the Akt
      signaling pathway in activated endothelial cells. The fact that these effects are
      carried out at lower concentrations than those required for other inhibitors of
      angiogenesis makes AD0157 a new promising drug candidate for further evaluation
      in the treatment of cancer and other angiogenesis-related pathologies. 

PMID- 24441616
TI  - Cross-translation of the job descriptive index: Validity and reliability
      procedure for the translation.
AB  - This study outlines a translation procedure for an attitudinal instrument. The
      study investigated the cross-translation of the Job Descriptive Index Sub scale
      of 'type of work.' The cross-translation or committee translation procedure asks
      two or more translators to translate a text from source to target language, then
      an expert assesses the validity of these translations. Empirically, this method
      has three translators, translate the instrument from English to Arabic and then
      an expert assesses the translations made by the three translators. This method
      was supported by having 180 bilinguals attempt the source language and later
      attempt the target language instrument or the translated instrument. The two
      versions are then compared through the ANOVA, correlational analyses and factor
      analyses. The results indicated a high reliability for the Arabic and English
      versions. The committee translation approach provides a valid method for
      translation, the results however, showed that the instrument in both languages
      did not show item to item similarity or equivalence. 

PMID- 24441614
TI  - Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering.
AB  - Over the last few years, significant research has been conducted in the
      construction of artificial bone scaffolds. In the present study, different types
      of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate
      with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and
      each was characterized as a bone graft substitute. The porosity, water uptake and
      retention ability of the prepared scaffolds showed similar efficacy. The pore
      size of the Chi-Alg and Chi-Alg-fucoidan scaffolds were measured from scanning
      electron microscopy and found to be 62-490 and 56-437 um, respectively. In vitro
      studies using the MG-63 cell line revealed profound cytocompatibility, increased
      cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg
      fucoidan scaffold compared to the Chi-Alg scaffold. Further, protein adsorption
      and mineralization were about two times greater in the Chi-Alg-fucoidan scaffold
      than the Chi-Alg scaffold. Hence, we suggest that Chi-Alg-fucoidan will be a
      promising biomaterial for bone tissue regeneration. 

PMID- 24441617
TI  - Work-related musculoskeletal symptoms among construction workers in the pipe
      trades.
AB  - Workers in the construction trades experience high rates of injuries and
      illnesses, including work-related musculoskeletal disorders. As the basis for
      formulating and implementing ergonomic changes to reduce musculoskeletal
      disorders among workers in the pipe trades, a cross-sectional survey was
      conducted. The survey instrument assessed the prevalence of work-related
      musculoskeletal symptoms and identified job factors that may contribute to those
      symptoms. A two-page questionnaire was mailed out to members of three plumber and
      pipe/steamfitter unions. Results from 526 (40% response rate) apprentices and
      journeymen indicated that the highest work-related symptoms and reported lost
      work time due to those symptoms, were in the back, neck, and knees. Awkward
      postures and working in the same position for long periods were identified as the
      leading causes of work-related musculoskeletal symptoms. These results can be
      used to formulate appropriate intervention strategies for the reduction of
      musculoskeletal symptoms for construction workers in the pipe trades. 

PMID- 24441618
TI  - Schizophrenia: strategies for rehabilitation professionals.
AB  - Vocational planning for people with schizophrenia often creates a unique
      challenge for rehabilitation professionals due to the ambiguous nature of the
      disease and the lack of information concerning the work potential of people with
      this disorder. This article reviews the medical, psychosocial, and vocational
      aspects of schizophrenia. Issues pertaining to difficulties in determining
      diagnoses and prognoses are discussed. Methods for assessment and vocational
      planning are also presented to assist rehabilitation professionals in making
      timely and appropriate interventions. 

PMID- 24441619
TI  - Literacy in the health professions today.
AB  - Multiple literacies are needed to be successful in the health professions today.
      This article outlines five general types or spheres of literacies that health
      care workers, professionals and clients need to possess to some degree to
      function effectively in the current complexities and multiple areas of modern
      health. Examples of each kind or sphere of literacy are given as well as
      suggestions for how such literacies may be promoted in the workplace. 

PMID- 24441620
TI  - A program to facilitate retention of employment among persons with multiple
      sclerosis.
AB  - OBJECTIVES: The objective was to develop and evaluate the feasibility of a
      medical-community job-retention model in MS. STUDY DESIGN: 43 individuals with MS
      at risk for losing their jobs were randomized to one of two groups. Both received
      standard medical care. The experimental group received specialized services
      geared toward job-retention conducted by medical personnel and an employment
      specialist. The control group received only standard medical care. Both groups
      were followed for 1 year. RESULTS: The new program was feasible, however,
      participants made little use of its services. At the I-year follow-up there was
      no difference between the two groups in job retention. CONCLUSIONS: A combined
      medical-community job-retention program is feasible in MS. However, patients do
      not generally wish to take advantage of job-retention services until an
      employment crisis develops. Future programs should develop more effective
      approaches to early intervention to realize their maximum potential.

PMID- 24441621
TI  - Evaluation of a vocational training programme in primary health care
      rehabilitation: a case study.
AB  - The content and effect of a new occupational therapy programme aimed for
      vocational training forming part of a research project named 'the Sollentuna
      Rehabilitation Project' are described for four patients (of 38) with
      musculoskeletal pain. In the programme, occupational therapy analysis and
      intervention alternated. Intervention was based on the model of human occupation,
      the rehabilitative, the biomechanical, and occupational adaptive frames of
      reference. Each patient participated in a structured interview and a job
      analysis. The programme was evaluated on five measurement occasions using the
      Goal Attainment Scale, self-assessments of patterns of daily occupation using an
      activity log, and self-estimation of pain using the 'Symtrack' instrument. On the
      fifth measurement occasion two of the patients had decreased their resting time
      and three were performing activities formerly avoided due to pain. Two patients'
      degree of assessed pain had decreased. Three of the four patients had attained
      their individual goals of occupational therapy (T= >50). The occupational therapy
      programme has proved to be applicable in primary health care for patients with
      musculoskeletal pain. 

PMID- 24441622
TI  - An investigation into the vocational rehabilitation practices provided by brain
      injury services throughout the United Kingdom.
AB  - The purpose of this research is to investigate the contributions and process of
      vocational rehabilitation in health based brain injury services in the United
      Kingdom. It addresses traditional forms of vocational rehabilitation and job
      coaching. In relation to these approaches, the research focuses on the process of
      assessment, intervention and outcome. It also identifies which staff are involved
      in vocational rehabilitation and reasons why some services do not address
      vocation. Data was gathered via a postal survey questionnaire. Of the 70 services
      who agreed to participate, 54 responded. The raw information provided a variety
      of nominal, ordinal and interval data and was mainly subjected to descriptive
      analysis. The results suggest that there is a limited range of suitable
      assessments and outcome measures that can be used in relation to vocational
      rehabilitation. In contrast, there is a dearth of intervention methods being
      implemented. Occupational therapists, followed by psychologists constitute the
      main disciplines involved in this provision. Reasons for not providing vocational
      rehabilitation are commonly due to insufficient staff, training and funding. 

PMID- 24441623
TI  - Hindering the work of the child: a perspective on orphanages.

PMID- 24441625
TI  - Phytotoxicity of atrazine to emergent hydrophyte, Iris pseudacorus L.
AB  - The emergent hydrophyte Iris pseudacorus was constantly exposed over a 35-day
      period to atrazine in the laboratory. It could survive at an atrazine level up to
      32 mg/L. Its relative growth rates were inhibited significantly when exposure
      dosage reached at or exceeded 2 mg/L (p < 0.05). No observed effect concentration
      and lowest observed effect concentration for growth were 1 and 2 mg/L,
      respectively. Chlorophyll a and b contents of the plant in all treatment groups
      were affected significantly, and chlorophyll a/b ratios of all atrazine treatment
      levels were pronouncedly higher than those of the control within 5 days of
      exposure (p < 0.05), but thereafter recovered to the level of the control.
      Differences of photosynthetic efficiency were significant between all atrazine
      treatments and the control; except for 1 mg/L on day 1 and 5, and 2 mg/L on day
      1. I. pseudacorus did not show phytotoxicity symptoms after 35 days exposure to
      atrazine below 2 mg/L level, but photosynthetic efficiency had begun to decline.

PMID- 24441626
TI  - Application of a redox gradostat reactor for assessing rhizosphere microorganism
      activity on lambda-cyhalothrin.
AB  - Bacterial activity on pesticides can lead to decreased toxicity or persistence in
      aquatic systems. Rhizosphere activity is difficult to measure in situ. To mimic
      rhizosphere properties of the soft rush, Juncus effusus, a single-stage gradostat
      reactor was developed to study cycling of lambda-cyhalothrin by rhizobacteria and
      the effects of Fe(III) and citrate, both common in wetland soil, on lambda
      cyhalothrin degradation. Redox gradient changes, greater than +/- 10 mV, were
      apparent within days 5-15 both in the presence and absence of ferric citrate.
      Through the production of a redox gradient (p < 0.05) by rhizobacteria and the
      ability to measure pesticide loss over time (p < 0.05), reactors were useful in
      expanding knowledge on this active environment.

PMID- 24441628
TI  - Put your thinking caps on.

PMID- 24441627
TI  - Spectral demultiplexing in holographic and fluorescent on-chip microscopy.
AB  - Lensfree on-chip imaging and sensing platforms provide compact and cost-effective
      designs for various telemedicine and lab-on-a-chip applications. In this work, we
      demonstrate computational solutions for some of the challenges associated with
      (i) the use of broadband, partially-coherent illumination sources for on-chip
      holographic imaging, and (ii) multicolor detection for lensfree fluorescent on
      chip microscopy. Specifically, we introduce spectral demultiplexing approaches
      that aim to digitally narrow the spectral content of broadband illumination
      sources (such as wide-band light emitting diodes or even sunlight) to improve
      spatial resolution in holographic on-chip microscopy. We also demonstrate the
      application of such spectral demultiplexing approaches for wide-field imaging of
      multicolor fluorescent objects on a chip. These computational approaches can be
      used to replace e.g., thin-film interference filters, gratings or other optical
      components used for spectral multiplexing/demultiplexing, which can form a
      desirable solution for cost-effective and compact wide-field microscopy and
      sensing needs on a chip. 

PMID- 24441637
TI  - Cancer therapy: Altering mitochondrial properties.

PMID- 24441638
TI  - Regenerative medicine: Of fish and men.

PMID- 24441643
TI  - Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young
      male Zucker diabetic fatty rats.
AB  - The use of melatonin, a neurohormone present in plants, represents an exciting
      approach for the maintenance of optimum health conditions. Melatonin
      administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF)
      rats. The objective of this study was to investigate the effects of melatonin in
      diabetes in relation to the levels and regulation of plasma chromium (Cr),
      vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean
      (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each
      subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10)
      and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week
      period. After treatment, plasma mineral concentrations were measured by flame
      (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant
      differences were found between the C and V' groups (p > 0.05). Plasma Mg levels
      were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of
      hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were
      significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were
      not affected by melatonin treatment (p > 0.05). Melatonin administration
      ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V
      concentrations. This appears to be the first report of a beneficial effect of
      melatonin treatment on plasma Cr and V regulation in ZDF rats. 

PMID- 24441644
TI  - Mortality in systemic sclerosis: lessons learned from population-based and
      observational cohort studies.
AB  - PURPOSE OF REVIEW: Systemic sclerosis (SSc) has a case-based mortality that is
      one of the highest among the rheumatic diseases. This article is an appraisal of
      current knowledge regarding survival, causes of death and risk factors for
      reduced life-expectancy in systemic sclerosis (SSc). RECENT FINDINGS: Recent
      systematic reviews of cohorts studies published worldwide have revealed a pooled
      standardized mortality ratio in SSc of 3.5, and reiterated the importance of
      heart-lung involvement as a major cause of death in this disease. Indeed, the
      pooled hazard ratio (HR) of mortality in SSc patients with pulmonary arterial
      hypertension (PAH) compared with those without is 3.5, while the pooled HR for
      mortality in those with interstitial lung disease is 2.6. The average life
      expectancy of patients with SSc is 16-34 years less than age-matched and sex
      matched population peers. Current research efforts are focused on quantifying
      early as well as late mortality, and modeling for predictors of death in SSc,
      with the ultimate goal of attenuating this risk and improving survival, as new
      therapies emerge. SUMMARY: Studies have consistently shown a substantially
      increased mortality in SSc, predominantly due to cardio-pulmonary complications.
      A better understanding of risk factors for mortality holds the promise of
      improving outcomes in this devastating multiorgan autoimmune disease.

PMID- 24441645
TI  - Do changes in objective and subjective family income predict change in children's
      diets over time? Unique insights using a longitudinal cohort study and fixed
      effects analysis.
AB  - BACKGROUND: While an association has been established between low income and poor
      diet using cross-sectional data, such analysis cannot account for confounding by
      unobserved characteristics correlated with income and diet, and changes in income
      and diet cannot be tracked over time. This paper, using longitudinal panel data,
      explores whether falls in objective and subjective family income predict
      deterioration in children's diets over time. METHODS: This paper uses panel data
      from the nationally representative birth cohort study Growing Up in Scotland.
      3279 families have valid data on all dependent, independent and control variables
      for both time points. Dietary data were collected using maternal recall at sweeps
      2 and 5 when the children were aged 22 and 58 months, respectively. Mothers
      reported on children's variety of consumption of vegetables, fruit and on the
      frequency of consumption of crisps, sweets and sugary drinks. The dietary
      variables were ordinal and were analysed using multivariate fixed effects ordinal
      logistic regression models. RESULTS: Controlling for time-varying confounders
      (children's food fussiness, maternal social class, maternal education, family
      composition, maternal employment) and for family and child time-invariant
      characteristics, moving from the highest to the lowest income band was linked to
      a smaller chance of increased fruit variety from 22 to 58 months (OR=0.42, 95% CI
      0.21 to 0.82). Mothers who transitioned from 'living very comfortably' to
      'finding it very difficult' to cope on current income had children who consumed
      fewer fruit varieties over time (OR=0.40, 95% CI 0.19 to 0.85), and who increased
      their frequency of consumption of crisps (OR=2.03, 95% CI 1.05 to 3.94) and
      sweets (OR=2.23, 95% CI 1.18 to 4.20). CONCLUSIONS: The diets of young children
      in Scotland deteriorated between the ages of 2 and 5 years across the entire
      socioeconomic spectrum. Additionally, deterioration in subjective income
      predicted less healthy diets for children.

PMID- 24441646
TI  - The Role of Historical Bioactivity Data in the Deconvolution of Phenotypic
      Screens.
AB  - A substantial challenge in phenotypic drug discovery is the identification of the
      molecular targets that govern a phenotypic response of interest. Several
      experimental strategies are available for this, the so-called target
      deconvolution process. Most of these approaches exploit the affinity between a
      small-molecule compound and its putative targets or use large-scale genetic
      manipulations and profiling. Each of these methods has strengths but also
      limitations such as bias toward high-affinity interactions or risks from genetic
      compensation. The use of computational methods for target and mechanism of action
      identification is a complementary approach that can influence each step of a
      phenotypic screening campaign. Here, we describe how cheminformatics and
      bioinformatics are embedded in the process from initial selection of a focused
      compound library from a large set of historical small-molecule screens through
      the analysis of screening results. We present a deconvolution method based on
      enrichment analysis and using known bioactivity data of screened compounds to
      infer putative targets, pathways, and biological processes that are consistent
      with the observed phenotypic response. As an example, the approach is applied to
      a cellular screen aiming at identifying inhibitors of tumor necrosis factor-alpha
      production in lipopolysaccharide-stimulated THP-1 cells. In summary, we find that
      the approach can contribute to solving the often very complex target
      deconvolution task. 

PMID- 24441648
TI  - Raman characterization of pseudocapacitive behavior of polypyrrole on nanoporous
      gold.
AB  - The practical applications of high-capacitance polypyrrole (PPy) as an active
      material for electrochemical supercapacitors are mainly limited by their poor
      cycling stability. By utilizing nanoporous gold enhanced Raman scattering of PPy,
      we investigated ex situ and in situ the structural origins of the low
      electrochemical stability of PPy. This study provided direct evidence that the
      stability degradation of PPy is caused by the irreversible transition between
      oxidation and reduction states of PPy, which is associated with the permanent
      deformation of PPy molecular chains subjected to applied potentials. 

PMID- 24441647
TI  - An Overview of the Challenges in Designing, Integrating, and Delivering BARD: A
      Public Chemical-Biology Resource and Query Portal for Multiple Organizations,
      Locations, and Disciplines.
AB  - Recent industry-academic partnerships involve collaboration among disciplines,
      locations, and organizations using publicly funded "open-access" and proprietary
      commercial data sources. These require the effective integration of chemical and
      biological information from diverse data sources, which presents key informatics,
      personnel, and organizational challenges. The BioAssay Research Database (BARD)
      was conceived to address these challenges and serve as a community-wide resource
      and intuitive web portal for public-sector chemical-biology data. Its initial
      focus is to enable scientists to more effectively use the National Institutes of
      Health Roadmap Molecular Libraries Program (MLP) data generated from the 3-year
      pilot and 6-year production phases of the Molecular Libraries Probe Production
      Centers Network (MLPCN), which is currently in its final year. BARD evolves the
      current data standards through structured assay and result annotations that
      leverage BioAssay Ontology and other industry-standard ontologies, and a core
      hierarchy of assay definition terms and data standards defined specifically for
      small-molecule assay data. We initially focused on migrating the highest-value
      MLP data into BARD and bringing it up to this new standard. We review the
      technical and organizational challenges overcome by the interdisciplinary BARD
      team, veterans of public- and private-sector data-integration projects, who are
      collaborating to describe (functional specifications), design (technical
      specifications), and implement this next-generation software solution. 

PMID- 24441649
TI  - Computationally efficient magnetic resonance imaging based surface contact
      modeling as a tool to evaluate joint injuries and outcomes of surgical
      interventions compared to finite element modeling.
AB  - Joint injuries and the resulting posttraumatic osteoarthritis (OA) are a
      significant problem. There is still a need for tools to evaluate joint injuries,
      their effect on joint mechanics, and the relationship between altered mechanics
      and OA. Better understanding of injuries and their relationship to OA may aid in
      the development or refinement of treatment methods. This may be partially
      achieved by monitoring changes in joint mechanics that are a direct consequence
      of injury. Techniques such as image-based finite element modeling can provide in
      vivo joint mechanics data but can also be laborious and computationally
      expensive. Alternate modeling techniques that can provide similar results in a
      computationally efficient manner are an attractive prospect. It is likely
      possible to estimate risk of OA due to injury from surface contact mechanics data
      alone. The objective of this study was to compare joint contact mechanics from
      image-based surface contact modeling (SCM) and finite element modeling (FEM) in
      normal, injured (scapholunate ligament tear), and surgically repaired radiocarpal
      joints. Since FEM is accepted as the gold standard to evaluate joint contact
      stresses, our assumption was that results obtained using this method would
      accurately represent the true value. Magnetic resonance images (MRI) of the
      normal, injured, and postoperative wrists of three subjects were acquired when
      relaxed and during functional grasp. Surface and volumetric models of the
      radiolunate and radioscaphoid articulations were constructed from the relaxed
      images for SCM and FEM analyses, respectively. Kinematic boundary conditions were
      acquired from image registration between the relaxed and grasp images. For the
      SCM technique, a linear contact relationship was used to estimate contact
      outcomes based on interactions of the rigid articular surfaces in contact. For
      FEM, a pressure-overclosure relationship was used to estimate outcomes based on
      deformable body contact interactions. The SCM technique was able to evaluate
      variations in contact outcomes arising from scapholunate ligament injury and also
      the effects of surgical repair, with similar accuracy to the FEM gold standard.
      At least 80% of contact forces, peak contact pressures, mean contact pressures
      and contact areas from SCM were within 10 N, 0.5 MPa, 0.2 MPa, and 15 mm2,
      respectively, of the results from FEM, regardless of the state of the wrist.
      Depending on the application, the MRI-based SCM technique has the potential to
      provide clinically relevant subject-specific results in a computationally
      efficient manner compared to FEM.

PMID- 24441651
TI  - [Reconstructions after inveterated fractures and dislocations of the foot].
AB  - Inveterated fractures or dislocations of the foot which are defined as being more
      than 6-12 weeks old can be secondarily reconstructed anatomically in only very
      rare cases. All other cases need reorientation of all axes of the foot requiring
      single or combined joint fusion. In cases of significant posttraumatic bone
      necrosis the dead bone has to be radically resected and substituted by an
      autogenous bone graft from the iliac crest. Old cases of dislocation, for example
      after subtalar dislocation without anatomical reduction, need reorientation of
      the foot axes by performing arthrodesis. Subluxation of the medial Lisfranc joint
      after an unrecognized rupture of Lisfranc ligament can be controlled later by
      anatomical repair of this ligament by using half of the extensor digitorum longus
      tendon and thus avoiding arthrodesis. 

PMID- 24441652
TI  - Clinical characteristics and prognostic factors in dogs with histiocytic sarcomas
      in Japan.
AB  - Canine histiocytic sarcoma (HS) is a rare neoplasm that originates from dendritic
      cells or macrophages, and there have been a number of cases experienced in Japan.
      To identify the characteristics and prognostic variables that determine outcome
      in dogs with HS in Japan, medical records of 73 dogs with HS were retrospectively
      analyzed. Signalment, clinical signs, complete blood count (CBC), blood chemistry
      profiles, treatment, response to treatment and overall survival (OS) were
      analyzed. Diagnosis of HS was determined histologically in 44 cases and
      cytologically in 29 cases. The most frequently diagnosed breeds were Flat-Coated
      Retrievers (n=16, odds ratio [OR] 62.0), Pembroke Welsh corgis (n=15, OR 9.7) and
      Bernese Mountain dogs (n=14, OR 45.0). Median survival time for all dogs in this
      study was 43 days. In the dogs that received no treatment or only symptomatic
      treatment, the median OS was 12 days (range 2-254 days) compared with that of
      dogs that received surgical treatment and/or chemotherapy (85 days, range 4-360
      days). Univariate analysis identified anemia, thrombocytopenia, hypoalbuminemia,
      hypoproteinemia and not receiving antitumor treatment (chemotherapy and/or
      surgery) as factors significantly associated with shorter OS. Multivariate
      analysis confirmed that platelet counts, localized/disseminated lesional pattern
      and whether the dog received antitumor treatment were significantly predictive of
      survival. 

PMID- 24441653
TI  - Synthesis, crystal structure and anti-fatigue effects of some benzamide
      derivatives.
AB  - A series of benzamide derivatives such as 1-(1,3-benzodioxol-5-ylcarbonyl)
      piperidine (1-BCP) were synthesized by the reaction of substituted benzoic acids
      with piperidine, morpholine or pyrrolidine using a novel method. The crystals of
      these benzamide derivatives were obtained by recrystallization. Structures of
      target and intermediate compounds were determined via FT-IR, 1H-NMR and elemental
      analysis and X-ray crystallography of select examples. The crystal structures of
      these compounds have potential applications to identify the binding site for
      allosteric modulators of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA) receptor. The anti-fatigue effects of the benzamide derivatives in
      weight-loaded forced swimming mice were investigated in a swimming endurance
      capacity test used as an indicator of fatigue. The swimming times to exhaustion
      were longer in the b3, d3, and e3 groups than in the caffeine group (p<0.05). In
      conclusion, b3, d3 and e3 enhanced the forced swimming capacity of mice. The
      mechanism of the anti-fatigue effects will be studied in the future.

PMID- 24441654
TI  - Microbiological and nutritional quality of the goat meat by-product "sarapatel".
AB  - Goat "sarapatel" is a product made from blood and viscera. For the first time,
      the microbiological and nutritional quality of "sarapatel" samples (n=48) sold
      under different conditions (in street markets, butcher shops, and supermarkets
      under refrigeration, frozen or at room temperature) was evaluated. Goat
      "sarapatel" is a nutritive food, with each 100 g providing, on average, 72 g of
      moisture, 2 g of ash, 18 g of protein, 9 g of lipids, 2 g of carbohydrates, 282
      mg of cholesterol, and high amounts of unsaturated fatty acids and essential
      amino acids. The analysis of the "sarapatel" samples shows that none of them
      contain Salmonella spp. or L. monocytogenes. High counts (>104) of total
      coliforms, thermotolerant coliforms, and sulfite-reducing Clostridium were
      detected, and coagulase-positive Staphylococcus was found in 31.25% of samples.
      The storage conditions evaluated (refrigeration, frozen or at room temperature)
      did not affect the physicochemical quality of the "sarapatel"; however, the
      unsatisfactory microbiological quality indicates that it is necessary to improve
      the health-sanitary aspects of the processing and sale of this product.

PMID- 24441655
TI  - Analgesic effect of Harpagophytum procumbens on postoperative and neuropathic
      pain in rats.
AB  - Harpagophytum procumbens, also known as Devil's Claw, has historically been used
      to treat a wide range of conditions, including pain and arthritis. The study was
      designed to investigate whether H. procumbens extracts exhibit analgesic effects
      in plantar incision and spared nerve injury (SNI) rats. The whole procedure was
      performed on male SD rats. To evaluate pain-related behavior, we performed the
      mechanical withdrawal threshold (MWT) test measured by von Frey filaments. Pain
      related behavior was also determined through analysis of ultrasonic vocalization
      (USVs). The results of experiments showed MWT values of the group that was
      treated with 300 mg/kg H. procumbens extract increased significantly; on the
      contrary, the number of 22-27 kHz USVs of the treated group was reduced at 6 h
      and 24 h after plantar incision operation. After 21 days of continuous treatment
      with H. procumbens extracts at 300 mg/kg, the treated group showed significantly
      alleviated SNI-induced hypersensitivity responses by MWT, compared with the
      control group. These results suggest that H. procumbens extracts have potential
      analgesic effects in the case of acute postoperative pain and chronic neuropathic
      pain in rats. 

PMID- 24441656
TI  - Fallopian tube intraluminal tumor spread.

PMID- 24441657
TI  - Papillary cystadenoma of the epididymis and broad ligament: morphologic and
      immunohistochemical overlap with clear cell papillary renal cell carcinoma.
AB  - Papillary cystadenoma is an uncommon epithelial tumor, originating within the
      head of the epididymis and broad ligament. When the lesion is bilateral, it is
      associated with von Hippel-Lindau disease. Its resemblance to metastatic clear
      cell renal cell carcinoma (RCC) has been noted in the literature. Owing to the
      emergence of additional markers for RCCs, we have evaluated the
      immunohistochemical staining patterns of a series of 7 papillary cystadenomas
      using CK7, RCC, PAX8, carbonic anhydrase IX, and AMACR. Six of the cases involved
      the epididymis, and 1 involved the broad ligament. The patients ranged in age
      from 20 to 65 years old. All of the tumors were unilateral and not known to be
      associated with von Hippel-Lindau disease. The lesions were composed of cystic
      structures, which focally contained papillary fibrovascular cores lined by
      cuboidal to columnar bland-appearing cells with clear cytoplasm. Another
      component was the presence of tubules, which focally had elongated profiles.
      Reverse polarity, wherein the nuclei are oriented toward the luminal surface with
      subnuclear vacuoles, was present focally in 4 cases and more extensively in a
      fifth case. Features associated with malignancy, such as mitotic figures, nuclear
      pleomorphism, and necrosis, were not identified. All lesions were strongly
      positive for CK7 and negative for RCC. Carbonic anhydrase IX was positive in all
      tumors (diffusely positive in 6, patchy in 1) with lack of staining in the apical
      portion of the cytoplasm (ie, cup-shaped staining). PAX8 showed diffuse
      positivity in 6 of the 7 lesions, with one of the epididymal cases showing
      negative staining. AMACR staining was negative in 5 of the 7 cases and showed
      only focal, weak staining in the remaining 2 cases. The current study more
      specifically demonstrated that papillary cystadenoma does not resemble clear cell
      RCC. Rather, papillary cystadenomas of the epididymis and broad ligament have
      identical morphology and immunohistochemical staining to clear cell papillary
      RCC. The diagnosis of papillary cystadenoma can be established as clear cell
      papillary RCC to date has not exhibited metastatic behavior. 

PMID- 24441658
TI  - Serous carcinogenesis: a classic causality dilemma or which came first... ?

PMID- 24441659
TI  - Tropical sprue: revisiting an underrecognized disease.
AB  - Tropical sprue is an acquired chronic diarrheal disorder of unclear etiology
      affecting residents of and visitors to tropical regions. Patients usually present
      with profuse diarrhea, weight loss, and malabsorption, notably of vitamin B12 and
      folate. The histologic changes typically resemble that of gluten-sensitive
      enteropathy. Reports of tropical sprue have become infrequent in the literature,
      and the diagnosis is often not considered either clinically or pathologically.
      This disease may, however, cause significant morbidity, although it is eminently
      treatable with broad-spectrum antibiotics. In this study, we report the clinical
      presentation of 12 tropical sprue patients along with the histologic changes of
      the intestinal mucosa and compare it with those of a series of 150 cases of
      gluten-sensitive enteropathy, the condition with which it is most frequently
      misdiagnosed. The cohort comprised 6 men and 6 women with a median age of 59
      years (range, 38 to 78 y) with a history of residence or visitation in South Asia
      or Papua New Guinea. Partial villous blunting in the duodenal mucosa was present
      in 75% of cases, and a marked intraepithelial lymphocytosis was observed in all
      cases (mean per 100 epithelial cells 77.3; range, 42 to 124). A villous tip
      accentuation of intraepithelial lymphocytosis was not appreciable in most cases.
      No case of complete villous blunting (Marsh stage 3c) was identified in tropical
      sprue, contrasting with 25% in gluten-sensitive enteropathy cases. A duodenal
      mucosa eosinophil infiltrate was present in all cases with significantly higher
      counts compared with untreated gluten-sensitive enteropathy patients (26.6/HPF
      vs. 14.6/HPF; P=0.009). The ileal mucosa displayed more severe villous blunting
      with higher Marsh stages than in the corresponding duodenum from 5 patients.
      There was a mild intraepithelial lymphocytosis and eosinophil infiltrate in the
      colonic mucosa of half of the cases. Follow-up biopsies in 6 patients
      demonstrated a histologic response after oral folates and doxycycline treatment.
      In summary, tropical sprue is a pan-enteric inflammatory process often mistaken
      for gluten-sensitive enteropathy. Histologic findings suggesting tropical sprue
      in the appropriate clinical context include incomplete duodenal villous blunting
      without development of flat mucosa, frequent involvement of the terminal ileum
      with more marked inflammation and villous blunting than in the duodenum, and a
      conspicuous eosinophil infiltrate in the lamina propria. With the expansion of
      tourism and increasing employment opportunities in tropical regions, pathologists
      in the West are increasingly likely to encounter cases of tropical sprue and
      should be aware of this diagnosis. 

PMID- 24441660
TI  - Lung cancer histologic and immunohistochemical heterogeneity in the era of
      molecular therapies: analysis of 172 consecutive surgically resected, entirely
      sampled pulmonary carcinomas.
AB  - On the basis of seminal studies in the 1980s, appreciable histologic
      heterogeneity, ranging from 45% to 70% of cases, may be encountered in lung
      cancer. However, the epidemiologic and histologic landscape of lung cancer in the
      last 3 decades has radically changed. In this study, 172 consecutive surgically
      resected primary lung carcinomas evaluated from 2010 to 2012 were entirely
      sampled and examined according to current histologic classifications. In 129
      cases, a positive preoperative biopsy was also available. Major histologic
      heterogeneity (a single tumor showing at least 2 different histologic types) and
      minor histologic heterogeneity (a single tumor showing just 1 histologic type but
      at least 2 different growth patterns) were evaluated in all cases.
      Immunohistochemical heterogeneity (ie, "aberrant" staining) was also assessed
      using a panel of markers of adenocarcinoma (TTF-1, napsin, and CK7), squamous
      cell carcinoma (p63, CK5/6), and neuroendocrine differentiation (chromogranin and
      synaptophysin), both on positive biopsies and surgical specimens. Overall, major
      and minor histologic heterogeneity on resections were disclosed in 4% (7 cases)
      and 50.6% (87 cases), respectively, whereas just 1 case of minor heterogeneity
      (pleomorphic carcinoma) was observed on biopsies. Minor heterogeneity was limited
      to adenocarcinomas (82.6%, 81/98 cases) and sarcomatoid carcinomas (6 pleomorphic
      types among 8 sarcomatoid carcinomas). Immunohistochemical heterogeneity was
      recorded in 22.6% of the cases, with expression of p63 and CK5/6 in a subset of
      adenocarcinomas (25 cases, 25.5%), CK7 in 17.4% of squamous cell carcinomas, and
      synaptophysin in 6 cases of non-neuroendocrine tumors (4%, 6/155). The high rate
      of adenocarcinomas, accounting for 57% (98 cases) of 172 consecutively resected
      lung cancers, reflects the new scenario of thoracic oncology and may explain the
      significant lower rate of major histologic heterogeneity (4%) and the higher
      frequency of different architectural patterns (minor heterogeneity) that we found
      in lung cancer compared with previous studies. 

PMID- 24441661
TI  - Evaluation of microinvasion and lymph node involvement in ovarian serous
      borderline/atypical proliferative serous tumors: a morphologic and
      immunohistochemical analysis of 37 cases.
AB  - Most of the literature on serous borderline/atypical proliferative serous tumors
      (SBT/APSTs) shows no effect of microinvasion or lymph node involvement on
      outcome. This study is a morphologic and immunohistochemical analysis of the
      cells comprising SBT/APSTs, microinvasion, lymph node involvement, and low-grade
      serous carcinoma (LGSC) in an attempt to explain this unusual behavior. We found
      that the cells in microinvasion and in lymph nodes were morphologically similar
      to the cells in SBT/APSTs but differed significantly from the cells in LGSCs. In
      addition, one particular population of cells, those with abundant eosinophilic
      cytoplasm (eosinophilic cells), in SBT/APSTs, microinvasion, and lymph nodes
      showed a significant loss of expression of ER, PR, and WT-1 compared with the
      cuboidal/columnar tumor cells, both in cases of microinvasion (P<0.001 for all 3
      markers) and lymph node involvement (P<0.001, P=0.02, P=0.002, respectively).
      There was a significant decrease in the Ki-67 proliferation index for
      microinvasion (P=0.004) and a decreasing trend for lymph node involvement
      (nonsignificant) compared with the columnar/cuboidal cells. In addition, cells in
      these tumors showed morphologic evidence of apoptosis, which was confirmed by
      immunostaining with M30, a marker of apoptosis. In contrast, LGSCs lacked
      eosinophilic cells and showed no loss of expression of ER, PR, and WT-1. They
      also had a significantly higher Ki-67 proliferation index than their associated
      SBT/APSTs (P=0.029). On the basis of these findings, we propose that the cells
      comprising microinvasion do not represent an invasive neoplastic process.
      Instead, in view of the loss of expression of ER, PR, and WT-1, evidence of
      apoptosis, and decrease in the Ki-67 proliferation index, we postulate that they
      are senescent and terminally differentiated with a subset of cells undergoing
      apoptosis, which could explain their lack of an adverse effect on outcome. 

PMID- 24441662
TI  - Blastic plasmacytoid dendritic cell neoplasms: clinico-immunohistochemical
      correlations in a series of 91 patients.
AB  - Blastic plasmacytoid dendritic cell neoplasm is a rare clinicopathologic entity,
      characterized by strong skin tropism and a poor prognosis. The diagnosis is
      generally made by skin biopsy with appropriate immunohistochemical studies. To
      identify potential biological prognostic factors for blastic plasmacytoid
      dendritic cell neoplasm, we performed an extended clinico-immunohistochemical
      study on a series of 91 well-documented cases collected since 1995 by the French
      Study Group on Cutaneous Lymphomas. Skin biopsies were analyzed using a panel of
      12 immunohistochemical markers (CD4, CD56, CD123, CD303, TCL1, CD68, CD2, CD7,
      TdT, Ki-67, S100, and MX-1). The results were correlated with survival. The 5
      most characteristic markers of this entity (CD4, CD56, CD123, CD303, and TCL1)
      were expressed simultaneously in only 46% of patients. However, when 4 markers
      were expressed the diagnosis could still be reliably made without resorting to
      any additional stains. Expression of TdT and/or S100 correlated with varying
      degrees of maturation. Statistical survival analyses showed that CD303 expression
      and high proliferative index (Ki-67) were significantly associated with longer
      survival. 

PMID- 24441664
TI  - Lobular neoplasia of the breast revisited with emphasis on the role of E-cadherin
      immunohistochemistry.

PMID- 24441663
TI  - Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal
      cancer: recognition of the syndrome by pathologic features and the utility of
      detecting aberrant succination by immunohistochemistry.
AB  - Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an
      autosomal dominant disorder in which germline mutations of fumarate hydratase
      (FH) gene confer an increased risk of cutaneous and uterine leiomyomas and renal
      cancer. HLRCC-associated renal cancer is highly aggressive and frequently
      presents as a solitary mass. We reviewed the clinicopathologic features of 9
      patients with renal tumors presenting as sporadic cases but who were later proven
      to have FH germline mutations. Histologically, all tumors showed mixed
      architectural patterns, with papillary as the dominant pattern in only 3 cases.
      Besides papillary, tubular, tubulopapillary, solid, and cystic elements, 6 of 9
      tumors contained collecting duct carcinoma-like areas with infiltrating tubules,
      nests, or individual cells surrounded by desmoplastic stroma. Prominent
      tubulocystic carcinoma-like component and sarcomatoid differentiation were
      identified. Although all tumors exhibited the proposed hallmark of HLRCC (large
      eosinophilic nucleolus surrounded by a clear halo), this feature was often not
      uniformly present throughout the tumor. Prior studies have shown that a high
      level of fumarate accumulated in HLRCC tumor cells causes aberrant succination of
      cellular proteins by forming a stable chemical modification, S-(2-succino)
      cysteine (2SC), which can be detected by immunohistochemistry. We thus explored
      the utility of detecting 2SC by immunohistochemistry in the differential
      diagnosis of HLRCC tumors and other high-grade renal tumors and investigated the
      correlation between 2SC staining and FH molecular alterations. All confirmed
      HLRCC tumors demonstrated diffuse and strong nuclear and cytoplasmic 2SC
      staining, whereas all clear cell (184/184, 100%), most high-grade unclassified
      (93/97, 96%), and the large majority of "type 2" papillary (35/45, 78%) renal
      cell carcinoma cases showed no 2SC immunoreactivity. A subset of papillary (22%)
      and rare unclassified (4%) tumors showed patchy or diffuse cytoplasmic staining
      without nuclear labeling, unlike the pattern seen with confirmed HLRCC tumors.
      Sequencing revealed no germline or somatic FH alterations in 14 tumors that
      either exhibited only cytoplasmic 2SC staining (n=5) or were negative for 2SC
      (n=9), despite their HLRCC-like morphologic features. Our results emphasize the
      pivotal role of pathologic examination in the diagnosis of HLRCC patients and
      indicate immunohistochemical detection of 2SC as a useful ancillary tool in the
      differentiation of HLRCC renal tumors from other high-grade renal cell
      carcinomas. 

PMID- 24441665
TI  - Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma.
AB  - Sclerosing epithelioid fibrosarcoma (SEF) and low-grade fibromyxoid sarcoma
      (LGFMS) are 2 distinct types of sarcoma, with a subset of cases showing
      overlapping morphologic and immunohistochemical features. LGFMS is characterized
      by expression of the MUC4 protein, and about 90% of cases display a distinctive
      FUS-CREB3L2 gene fusion. In addition, SEF is often MUC4 positive, but is
      genetically less well studied. Fluorescence in situ hybridization (FISH) studies
      have shown involvement of the FUS gene in the majority of so-called hybrid
      LGFMS/SEF and in 10% to 25% of sarcomas with pure SEF morphology. In this study,
      we investigated a series of 10 primary tumors showing pure SEF morphology, 4
      cases of LGFMS that at local or distant relapse showed predominant SEF
      morphology, and 1 primary hybrid LGFMS/SEF. All but 1 case showed diffuse
      expression for MUC4. Using FISH, reverse transcription polymerase chain reaction,
      and/or mRNA sequencing in selected cases, we found recurrent EWSR1-CREB3L1 fusion
      transcripts by reverse transcription polymerase chain reaction in 3/10 pure SEF
      cases and splits and deletions of the EWSR1 and/or CREB3L1 genes by FISH in 6
      additional cases. All 5 cases of LGFMS with progression to SEF morphology or
      hybrid features had FUS-CREB3L2 fusion transcripts. Our results indicate that
      EWSR1 and CREB3L1 rearrangements are predominant over FUS and CREB3L2
      rearrangements in pure SEF, highlighting that SEF and LGFMS are different tumor
      types, with different impacts on patient outcome. 

PMID- 24441666
TI  - Dual mobility cup reduces dislocation and re-operation when used to treat
      displaced femoral neck fractures.
AB  - PURPOSE: Total hip arthroplasty (THA) as primary treatment for displaced femoral
      neck fractures is controversial as THA is associated with higher rates of
      dislocation but lower rates of re-operation compared to hemiarthroplasty (HA). A
      dual mobility cup (DMC) design is associated with lower dislocation and re
      operation rates in elective surgery. Is this also the case when used to treat
      displaced femoral neck fractures? The aim of this study is to compare rates of
      dislocation and re-operation of any kind following treatment for displaced
      femoral neck fractures with either bipolar HA or THA with DMC. METHODS: Two
      consecutive groups of patients treated for displaced femoral neck fractures at
      the Regional Hospital in Viborg in Denmark were included. In 2007-2008 171
      patients (mean age 84.1 years) were treated with bipolar HA. In 2009-2010 175
      patients (mean age 75.2 years) were treated with THA with DMC. Data regarding
      rates of dislocation and re-operation were obtained by retrospective review of
      medical records. RESULTS: We found a statistically significant difference
      regarding rates of dislocation and re-operation of any kind in favour of THA with
      DMC. Dislocation occurred in 25/171 patients [95 % confidence interval (CI) 9.3
      19.9 %] treated with bipolar HA and 8/175 patients (95 % CI 1.5-7.7 %) treated
      with THA with DMC (p = 0.002). Re-operations were required in 32/171 patients (95
      % CI 12.9-24.6 %) treated with bipolar HA and 16/175 patients (95 % CI 4.8-13.4
      %) treated with THA with DMC (p = 0.01). CONCLUSIONS: Our findings indicate that
      THA with DMC is superior to bipolar HA following treatment for displaced femoral
      neck fractures in regard to rates of dislocation and re-operation.

PMID- 24441667
TI  - Expanding the pool of healthcare providers to perform penicillin skin testing in
      the ICU.

PMID- 24441668
TI  - Intensive care research and publication in India: quo vadis?

PMID- 24441669
TI  - The importance of word choice in the care of critically ill patients and their
      families.

PMID- 24441670
TI  - Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a
      multinational observational study.
AB  - PURPOSE: Recalibration and determining discriminative power, internationally, of
      the existing delirium prediction model (PRE-DELIRIC) for intensive care patients.
      METHODS: A prospective multicenter cohort study was performed in eight intensive
      care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent
      and admission category, infection, coma, sedation, morphine use, urea level,
      metabolic acidosis) were collected within 24 h after ICU admission. The confusion
      assessment method for the intensive care unit (CAM-ICU) was used to identify ICU
      delirium. CAM-ICU screening compliance and inter-rater reliability measurements
      were used to secure the quality of the data. RESULTS: A total of 2,852 adult ICU
      patients were screened of which 1,824 (64%) were eligible for the study. Main
      reasons for exclusion were length of stay <1 day (19.1%) and sustained coma
      (4.1%). CAM-ICU compliance was mean (SD) 82 +/- 16% and inter-rater reliability
      0.87 +/- 0.17. The median delirium incidence was 22.5% (IQR 12.8-36.6%). Although
      the incidence of all ten predictors differed significantly between centers, the
      area under the receiver operating characteristic (AUROC) curve of the eight
      participating centers remained good: 0.77 (95% CI 0.74-0.79). The linear
      predictor and intercept of the prediction rule were adjusted and resulted in
      improved re-calibration of the PRE-DELIRIC model. CONCLUSIONS: In this
      multinational study, we recalibrated the PRE-DELIRIC model. Despite differences
      in the incidence of predictors between the centers in the different countries,
      the performance of the PRE-DELIRIC-model remained good. Following validation of
      the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent
      delirium and aid improvements in delirium management of ICU patients.

PMID- 24441671
TI  - Chemoprevention of squamous cell carcinoma of the head and neck: no time to lose
      momentum.
AB  - The prospects for chemoprevention to reduce the incidence of squamous cell
      carcinoma of the head and neck (SCCHN) are great. The tissue at risk for
      harboring disease is relatively accessible for examination and biopsy. Patients
      appropriate for study can be easily identified by their risk factors and the
      presence of premalignant lesions. Our understanding of the pathogenesis of SCCHN
      is ever increasing, and offers new opportunities to explore strategies for
      prevention therapies. In this issue of Cancer Prevention Research, Saba and
      colleagues report on a phase Ib trial of celecoxib plus erlotinib to prevent
      progression to higher-grade dysplasia or invasive carcinoma in patients with oral
      premalignant lesions. The overall response rate was 57%, though by the time of
      last analysis, 85% of patients relapsed. In this commentary, challenges to the
      success of chemoprevention clinical trials for SCCHN, such as pitfalls in using
      surrogate biomarkers and reversal of histologic premalignant changes as study
      endpoints, are discussed. In addition, strategies to help ensure further
      development in the field of head and neck cancer prevention are reviewed. These
      include focusing efforts on tobacco cessation and human papillomavirus
      vaccination, targeting key molecular drivers of head and neck carcinogenesis, and
      focusing on combination strategies that have the potential to eradicate
      premalignant clones, even if some toxicity is encountered.

PMID- 24441672
TI  - The UK Lung Screen (UKLS): demographic profile of first 88,897 approaches
      provides recommendations for population screening.
AB  - The UK Lung Cancer Screening trial (UKLS) aims to evaluate low-dose computed
      tomography (LDCT) lung cancer population screening in the United Kingdom. In
      UKLS, a large population sample ages 50 to 75 years is approached with a
      questionnaire to determine lung cancer risk. Those with an estimated risk of at
      least 5% of developing lung cancer in the next 5 years (using the Liverpool Lung
      project risk model) are invited to participate in the trial. Here, we present
      demographic, risk, and response rate data from the first 88,897 individuals
      approached. Of note, 23,794 individuals (26.8% of all approached) responded
      positively to the initial questionnaire; 12% of these were high risk. Higher
      socioeconomic status correlated positively with response, but inversely with risk
      (P < 0.001). The 50- to 55-year age group was least likely to participate, and at
      lowest cancer risk. Only 5% of clinic attendees were ages <=60 years (compared
      with 47% of all 88,897 approached); this has implications for cost effectiveness.
      Among positive responders, there were more ex-smokers than expected from
      population figures (40% vs. 33%), and fewer current smokers (14% vs. 17.5%). Of
      note, 32.7% of current smokers and 18.4% of ex-smokers were designated as high
      risk. Overall, 1,452 of 23,794 positive responders (6.1%) were deemed high risk
      and attended a recruitment clinic. UKLS is the first LDCT population screening
      trial, selecting high-risk subjects using a validated individual risk prediction
      model. KEY FINDINGS: (i) better recruitment from ex- rather than current smokers,
      (ii) few clinic attendees ages early 50s, and (iii) representative number of
      socioeconomically deprived people recruited, despite lower response rates.

PMID- 24441673
TI  - Tazarotene: randomized, double-blind, vehicle-controlled, and open-label
      concurrent trials for basal cell carcinoma prevention and therapy in patients
      with basal cell nevus syndrome.
AB  - Sporadic human basal cell carcinomas (BCC) are generally well managed with
      current surgical modalities. However, in the subset of high-risk patients
      predisposed to developing large numbers of BCCs, there is an unmet need for
      effective, low-morbidity chemoprevention. This population includes fair-skinned
      patients with extensive sun exposure and those with genodermatoses such as the
      basal cell nevus (Gorlin) syndrome (BCNS). Tazarotene (Tazorac, Allergan) is a
      topical retinoid with relative specificity for RAR-beta and RAR-gamma receptors.
      We previously demonstrated tazarotene's robust anti-BCC efficacy in Ptch1(+/-)
      mice, a murine equivalent of BCNS, and others have found it to have some efficacy
      against sporadic human BCCs. We report here results of a randomized, double
      blind, vehicle-controlled study in patients with BCNS evaluating the efficacy of
      topically applied tazarotene for BCC chemoprevention (N = 34 subjects), along
      with an open-label trial evaluating tazarotene's efficacy for chemotherapy of BCC
      lesions (N = 36 subjects) for a maximum follow-up period of 3 years. We found
      that only 6% of patients had a chemopreventive response and that only 6% of
      treated BCC target lesions were clinically cured. Our studies provide no evidence
      for either chemopreventive or chemotherapeutic effect of tazarotene against BCCs
      in patients with BCNS.

PMID- 24441674
TI  - Requirement and epigenetics reprogramming of Nrf2 in suppression of tumor
      promoter TPA-induced mouse skin cell transformation by sulforaphane.
AB  - Nrf2 is a transcription factor that plays critical roles in regulating the
      expression of cellular defensive antioxidants and detoxification enzymes.
      However, the role of Nrf2 and Nrf2's epigenetics reprogramming in skin tumor
      transformation is unknown. In this study, we investigated the inhibitory role and
      epigenetics of Nrf2 on tumor transformation induced by 12-O-tetradecanoylphorbol
      13-acetate (TPA) in mouse skin epidermal JB6 (JB6 P+) cells and the anticancer
      effect of sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables.
      After five days of treatment, SFN significantly inhibited TPA-induced JB6
      cellular transformation and SFN enhanced the nuclear translocation of Nrf2 and
      increased the mRNA and protein levels of the Nrf2 target genes HO-1, NQO1 and
      UGT1A1. Knockdown of Nrf2 attenuated the induction of Nrf2, HO-1 and NQO1 by SFN,
      enhanced TPA-induced colony formation and dampened the inhibitory effect of SFN
      on TPA-induced JB6 transformation. Epigenetics investigation using bisulfite
      genomic sequencing showed that SFN decreased the methylation ratio of the first
      15 CpGs of the Nrf2 gene promoter, which was corroborated by increased Nrf2 mRNA
      expression. Furthermore, SFN strongly reduced the protein expression of DNA
      methyltransferases (DNMT1, DNMT3a and DNMT3b). SFN also inhibited the total
      histone deacetylase (HDAC) activity and decreased the protein expression of
      HDAC1, HDAC2, HDAC3 and HDAC4. Collectively, these results suggest that the anti
      cancer effect of SFN against TPA-induced neoplastic transformation of mouse skin
      could involve the epigenetic reprogramming of anti-cancer genes such as Nrf2,
      leading to the epigenetic reactivation of Nrf2 and the subsequent induction of
      downstream target genes involved in cellular protection.

PMID- 24441675
TI  - Adherence to endocrine therapy in breast cancer adjuvant and prevention settings.
AB  - Adherence to oral endocrine therapy in adjuvant breast cancer settings is a
      substantial clinical problem. To provide current perspective on adherence to oral
      endocrine therapies, a comprehensive literature review was conducted. In adjuvant
      trials, endocrine therapy adherence is relatively high with greater adherence for
      aromatase inhibitors compared with tamoxifen. In contrast, adherence to adjuvant
      therapy in clinical practice is relatively poor, with only about 50% of women
      successfully completing 5-year therapy. Importantly, good adherence (>80% use)
      has been associated with lower recurrence risk. Endocrine therapy adherence in
      primary breast cancer prevention trials parallels that seen in adjuvant trials.
      Factors associated with nonadherence include low recurrence risk perception, side
      effects, age extremes, medication cost, suboptimal patient-physician
      communication, and lack of social support. Few prospective studies have evaluated
      interventions designed to improve adherence. Interventions currently proposed
      reflect inferences from clinical trial procedures in which clinical contacts are
      commonly greater than in usual practice settings. In conclusion, for optimal
      breast cancer outcome, adherence to endocrine therapy must improve. Although
      general recommendations likely to improve adherence can be made based on clinical
      trial results and preliminary prospective trial findings, research specifically
      targeting this issue is needed to establish effective intervention strategies.

PMID- 24441676
TI  - Excess weight gain accelerates 1-methyl-1-nitrosourea-induced mammary
      carcinogenesis in a rat model of premenopausal breast cancer.
AB  - In contrast to the null effects generally reported, high-risk premenopausal women
      (Gail score >=1.66) enrolled in the Breast Cancer Prevention P-1 Trial were
      recently reported to be at increased risk for breast cancer when overweight (HR =
      1.59) or obese (HR = 1.70). To investigate this clinical observation in a
      preclinical setting, ovary-intact female rats were intraperitoneally injected
      with 50 mg/kg 1-methyl-1-nitrosourea at 21 days of age to simulate premenopausal
      women with increased risk. Two commercially available strains of Sprague-Dawley
      rat (Taconic Farms) were used, which are dietary resistant (DR) or dietary
      susceptible (DS) to excess weight gain when fed a purified diet containing 32%
      kcal from fat, similar to levels consumed by the typical American woman. DS rats
      were approximately 15.5% heavier than DR rats at study termination and plasma
      leptin indicated a marked difference in adiposity. DS rats had higher incidence
      (26% increase), multiplicity (2.5-fold increase), and burden (5.4-fold increase)
      of mammary carcinomas with a concomitant reduction in cancer latency (16% earlier
      detection) compared with DR rats (P < 0.001 for all analyses), and displayed a
      higher proportion of hormone receptor negative tumors compared with DR rats [OR =
      1.78; 95% confidence interval (CI), 0.83-3.81]. Circulating levels of several
      breast cancer-risk factors, including leptin, adiponectin:leptin ratio, insulin,
      insulin-like growth factor (IGF)-1, IGF-1:IGF-1 binding protein-3 ratio, and
      calculated insulin resistance (HOMA-IR) were negatively impacted in DS rats (P <
      0.05 for all analyses). These findings support further investigation of the
      effects of excess weight in high-risk premenopausal women and demonstrate a
      useful preclinical model for rapid evaluation of mechanistic hypotheses.

PMID- 24441678
TI  - An alternative method for tracking a radioactive particle inside a fluid.
AB  - The proposed tracking method describes the trajectory of a radioactive particle
      moving in a fluid as a sequence of small cubic cells occupied by successive
      particle positions. In addition, the EM reconstruction algorithm was applied to
      get the image of the unique cell which had the greatest probability to contain
      the particle at a given time of a test. Next, this information was useful to
      calculate the coordinates and velocities of the particle at that time. The method
      was tested in laboratory using a gamma radiation detection system, the
      radioisotope (198)Au and a mixer. According to the results, the maximum deviation
      found between theoretical and experimental values of the average rotating period
      was less than 8% and the particle's reconstructed trajectories are representative
      of its real movement. Thus, a paradigm shift permitted us to begin the
      development of an alternative method to solve the complex problem of tracking the
      movement of a radioactive particle inside an opaque unit. 

PMID- 24441677
TI  - Class I HDACs are mediators of smoke carcinogen-induced stabilization of DNMT1
      and serve as promising targets for chemoprevention of lung cancer.
AB  - DNA methylation is an early event in bronchial carcinogenesis and increased DNA
      methyltransferase (DNMT)1 protein expression is a crucial step in the oncogenic
      transformation of epithelia. Here, we investigate the role of class I histone
      deacetylases (HDAC) 1 to 3 in the stabilization of DNMT1 protein and as a
      potential therapeutic target for lung cancer chemoprevention. Long-term exposure
      of immortalized bronchial epithelial cells (HBEC-3KT) to low doses of tobacco
      related carcinogens led to oncogenic transformation, increased HDAC expression,
      cell-cycle independent increased DNMT1 stability, and DNA hypermethylation.
      Overexpression of HDACs was associated with increased DNMT1 stability and
      knockdown of HDACs reduced DNMT1 protein levels and induced DNMT1 acetylation.
      This suggests a causal relationship among increased class I HDACs levels,
      upregulation of DNMT1 protein, and subsequent promoter hypermethylation.
      Targeting of class I HDACs with valproic acid (VPA) was associated with reduced
      HDAC expression and a profound reduction of DNMT1 protein level. Treatment of
      transformed bronchial epithelial cells with VPA resulted in reduced colony
      formation, demethylation of the aberrantly methylated SFRP2 promoter, and
      derepression of SFRP2 transcription. These data suggest that inhibition of HDAC
      activity may reverse or prevent carcinogen-induced transformation. Finally,
      immunohistochemistry on human lung cancer specimens revealed a significant
      increase in DNMT1, HDAC1, HDAC2, and HDAC3 expression, supporting our hypotheses
      that class I HDACs are mediators of DNMT1 stability. In summary, our study
      provides evidence for an important role of class I HDACs in controlling the
      stability of DNMT1 and suggests that HDAC inhibition could be an attractive
      approach for lung cancer chemoprevention.

PMID- 24441679
TI  - Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition
      in the retina.
AB  - The reciprocal synapse between photoreceptors and horizontal cells underlies
      lateral inhibition and establishes the antagonistic center-surround receptive
      fields of retinal neurons to enhance visual contrast. Despite decades of study,
      the signal mediating the negative feedback from horizontal cells to cones has
      remained under debate because the small, invaginated synaptic cleft has precluded
      measurement. Using zebrafish retinas, we show that light elicits a change in
      synaptic proton concentration with the correct magnitude, kinetics and spatial
      dependence to account for lateral inhibition. Light, which hyperpolarizes
      horizontal cells, causes synaptic alkalinization, whereas activating an
      exogenously expressed ligand-gated Na(+) channel, which depolarizes horizontal
      cells, causes synaptic acidification. Whereas acidification was prevented by
      blocking a proton pump, re-alkalinization was prevented by blocking proton
      permeant ion channels, suggesting that distinct mechanisms underlie proton efflux
      and influx. These findings reveal that protons mediate lateral inhibition in the
      retina, raising the possibility that protons are unrecognized retrograde
      messengers elsewhere in the nervous system. 

PMID- 24441680
TI  - Medial prefrontal D1 dopamine neurons control food intake.
AB  - Although the prefrontal cortex influences motivated behavior, its role in food
      intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor
      expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of
      feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and
      optogenetic photostimulation of D1 neurons increases feeding. Conversely,
      inhibition of D1 neurons decreases intake. Stimulation-based mapping of
      prefrontal D1 neuron projections implicates the medial basolateral amygdala
      (mBLA) as a downstream target of these afferents. mBLA neurons activated by
      prefrontal D1 stimulation are CaMKII positive and closely juxtaposed to
      prefrontal D1 axon terminals. Finally, photostimulating these axons in the mBLA
      is sufficient to increase feeding, recapitulating the effects of mPFC D1
      stimulation. These data describe a new circuit for top-down control of food
      intake. 

PMID- 24441683
TI  - Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic
      trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.
AB  - Evidences suggest that apple peel has a wide range of polyphenols having
      antioxidant activity and its consumption has been linked with improved health
      benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of
      acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated
      through alterations in various cardiac ion channels and by increasing the
      intracellular calcium level and reactive oxygen species (ROS). The aim of the
      present investigation was to study the effect of methanolic extract of apple peel
      (APME) and aqueous extract of apple peel (APAE) on ATO (5 MUM) induced toxicity
      in the H9c2 cardiac myoblast cell line. We estimated the cellular status of
      innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione
      and intracellular calcium with ATO and apple peel extracts. Prior to the cell
      line based study, we had evaluated the antioxidant potential of apple peel
      extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP),
      superoxide anion and hydroxyl radical scavenging activity, in addition to
      quantifying total phenolic and flavonoid content. Both the extracts showed
      considerable antioxidant activity in cell-free chemical assays. In addition, both
      APME and APAE prevented the alteration in antioxidant status induced by ATO in
      H9c2 cells. Significant differential alterations had been observed in the
      activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione,
      glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload
      and caspase 3 activity with ATO. The overall result revealed the protective
      property of polyphenol-rich apple peel extract against ATO induced cardiac
      toxicity via its antioxidant activity. 

PMID- 24441681
TI  - Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory
      deficiency.
AB  - Amyloid-induced microglial activation and neuroinflammation impair central
      synapses and memory function, although the mechanism remains unclear. Neuroligin
      1 (NLGN1), a postsynaptic protein found in central excitatory synapses, governs
      excitatory synaptic efficacy and plasticity in the brain. Here we found, in
      rodents, that amyloid fibril-induced neuroinflammation enhanced the interaction
      between histone deacetylase 2 and methyl-CpG-binding protein 2, leading to
      suppressed histone H3 acetylation and enhanced cytosine methylation in the Nlgn1
      promoter region and decreased NLGN1 expression, underlying amyloid-induced memory
      deficiency. Manipulation of microglia-associated neuroinflammation modulated the
      epigenetic modification of the Nlgn1 promoter, hippocampal glutamatergic
      transmission and memory function. These findings link neuroinflammation, synaptic
      efficacy and memory, thus providing insight into the pathogenesis of amyloid
      associated diseases. 

PMID- 24441684
TI  - Current challenges and future perspectives of radiotherapy for locally advanced
      breast cancer.
AB  - PURPOSE OF REVIEW: To discuss current issues in the field of radiation oncology
      for locally advanced breast cancer (LABC). RECENT FINDINGS: Large randomized
      studies involving nodal irradiation have recently been completed. The incremental
      benefit of treating the internal mammary nodes (IMNs) remains controversial. A
      randomized study specifically evaluating internal mammary node radiation (IMNR)
      failed to demonstrate significant benefit. A high impact, population-based study
      detected a proportional increase in major coronary events with increasing
      radiation dose. Advanced treatment techniques should be employed to reduce
      cardiac exposure. In patients with stage IV breast cancer (BCa), there is
      increasing evidence to suggest that locoregional treatments may improve overall
      survival (OS). Radiotherapy alone, without surgery, may provide equivalent local
      control and OS in patients with distant metastasis. High-dose stereotactic
      radiation regimens can be used to treat breast tumors with good local control
      rates in as few as three visits.BCa biomarkers are predictive of locoregional
      recurrence risk and should be used to guide radiotherapy in conjunction with
      standard staging. Clinically validated genetic profiling can measure tumor
      radiosensitivity and also help to predict normal tissue toxicity. SUMMARY: We are
      entering an era of personalized radiotherapy for LABC. Radiation treatments must
      be tailored to each individual patient's risk and intrinsic tumor biology.

PMID- 24441682
TI  - Tbr1 haploinsufficiency impairs amygdalar axonal projections and results in
      cognitive abnormality.
AB  - The neuron-specific transcription factor T-box brain 1 (TBR1) regulates brain
      development. Disruptive mutations in the TBR1 gene have been repeatedly
      identified in patients with autism spectrum disorders (ASDs). Here, we show that
      Tbr1 haploinsufficiency results in defective axonal projections of amygdalar
      neurons and the impairment of social interaction, ultrasonic vocalization,
      associative memory and cognitive flexibility in mice. Loss of a copy of the Tbr1
      gene altered the expression of Ntng1, Cntn2 and Cdh8 and reduced both inter- and
      intra-amygdalar connections. These developmental defects likely impair neuronal
      activation upon behavioral stimulation, which is indicated by fewer c-FOS
      positive neurons and lack of GRIN2B induction in Tbr1(+/-) amygdalae. We also
      show that upregulation of amygdalar neuronal activity by local infusion of a
      partial NMDA receptor agonist, d-cycloserine, ameliorates the behavioral defects
      of Tbr1(+/-) mice. Our study suggests that TBR1 is important in the regulation of
      amygdalar axonal connections and cognition. 

PMID- 24441686
TI  - From the editor.

PMID- 24441685
TI  - A geometrical approach explains Lake Ball (Marimo) formations in the green alga,
      Aegagropila linnaei.
AB  - An extremely rare alga, Aegagropila linnaei, is known for its beautiful spherical
      filamentous aggregations called Lake Ball (Marimo). It has long been a mystery in
      biology as to why this species forms 3D ball-like aggregations. This alga also
      forms two-dimensional mat-like aggregations. Here we show that forming ball-like
      aggregations is an adaptive strategy to increase biomass in the extremely limited
      environments suitable for growth of this alga. We estimate the maximum biomass
      attained by ball colonies and compare it to that attained by mat colonies. As a
      result, a ball colony can become larger in areal biomass than the mat colony. In
      the two large ball colonies studied so far, they actually have larger biomasses
      than the mat colonies. The uniqueness of Lake Balls in nature seems to be due to
      the rarity of such environmental conditions. This implies that the conservation
      of this alga is difficult, but important. 

PMID- 24441687
TI  - Hand and upper extremity trauma in high-level instrumentalists: epidemiology and
      outcomes.
AB  - Hand and upper extremity injuries to the professional or serious amateur musician
      may cause significant disability and time away from one's instrument. This
      article reviewed 222 instrumentalists; 201 were followed to an end result of
      their injuries. 80% played strings or keyboard instruments. Sports or a direct
      fall were the most common causes of injury. The spectrum of diagnoses made was
      typical of hand trauma in general; fractures, sprains, muscle strains and
      lacerations were the most numerous. Final results after treatment in 201 patients
      included complete relief of symptoms in 137 (68.2%) and improvement in another 61
      (30.3%). Return to performance was complete in 155 patients (77.1%) and in a
      modified fashion in 42 (20.9%). Only three performers had to stop playing as a
      result of trauma or it's sequelae. The 46 patients presenting with late sequelae
      of injury were less likely to achieve full restoration of function and complete
      return to musical activity than those who suffered acute trauma. Division of
      nerves or tendons, seen in 13 of 28 patients who sustained lacerations, was more
      likely to result in very long-term disability and/or incomplete recovery. 

PMID- 24441688
TI  - Return to play after injury: strategies to support a musician's recovery.
AB  - The treatment of musicians' injuries has two distinct, overlapping, phases.
      Reducing pain or symptoms represents only the first stage. Too often, this is the
      end of the medical care. If the player has had to stop playing or significantly
      reduce playing time during the healing phase, a graduated, methodical plan for
      returning to full musical activity is essential to avoid emotionally and
      physically distressing relapses. In the field of occupational medicine this
      concept is called 'work hardening'. The worker performs his or her specific
      tasks, but starts out at a greatly reduced level in terms of time and intensity.
      A graduated program for return to play is discussed in terms of duration, tempo
      and technical difficulty with specific recommendations for various instruments.
      Minor set backs are to be expected and the patient should be advised from the
      start that this is a normal part of the process so as to avoid discouragement.
      Following the principles set forth in this article will optimize the musicians'
      chances for smooth, successful return to normal musical activity. 

PMID- 24441689
TI  - Thoracic outlet syndromes: a non-surgeon's perspective for those caring for
      musicians.
AB  - The author reviews the history and clinical presentations of several distinct
      clinical conditions which together make up the group of patients referred to
      generally by the term 'thoracic outlet syndromes.' Although in specific cases the
      anatomy and pathophysiology of these patients correlate well, in most of them,
      those with the so-called 'disputed neurogenic' form, no such correlation has ever
      been proven. Thus, treatment of these patients is controversial. In the
      appropriately cautious management of these patients, surgical decompression of
      the thoracic outlet should never precede a trial of aggressive conservative
      therapy. This precept is particularly critical in musicians, because these
      patients require maximal degrees of mechanical freedom to play their instruments.

PMID- 24441690
TI  - Rehabilitation of anterior cruciate ligament insufficiency in a dancer using the
      clinical reformer and a balanced body exercise method.
AB  - Severe ligamentous knee injuries are uncommon in dance, but partial instability
      can be disabling. Because of the aesthetics required, use of a brace is not
      practical. The balanced body approach of exercise and rehabilitation can maximize
      the physiologic stabilizers of the knee and allow return to dance. While derived
      from the original principles of Joseph H. Pilates, current practitioners apply
      modern biomechanical and medical knowledge. The Reformer, a spring loaded
      exercise device first used by J.H. Pilates, can provide both a simulated
      environment for dance technique while allowing rest of the injured part and a
      method of cross training. 

PMID- 24441691
TI  - Thoracic outlet syndrome in musicians - an approach to treatment.
AB  - Thoracic outlet syndrome (TOS) can affect the skill of instrumental musicians.
      This paper details the way in which symptomatic TOS affects the musician and
      describes two cases of symptomatic TOS in a drummer and a violinist. Evaluation
      tools and treatment techniques are described. 

PMID- 24441692
TI  - An overview of upper extremity cumulative trauma disorders in pianists.
AB  - Many instrumentalists suffer from overuse syndrome due to repetitive and
      sustained motions required of the upper extremity. Overuse injuries in pianists
      are frequently caused by lack of rest breaks, deconditioned upper extremities,
      performance technique, and anatomical limitations of the hand and fingers. This
      article examines the precipitating factors of overuse syndrome through a case
      study approach. 

PMID- 24441693
TI  - Child labor: a global problem on the rise.
AB  - This paper intends to review and analyse the literature focusing on the topic of
      child labor. Child labor is a global problem on the rise despite modern Western
      beliefs. Today, such complex and interrelated issues as poverty, illiteracy, and
      politics fuel the growth of the number of children being exploited for economic
      gain. It is often difficult to imagine that the products we purchase are
      manufactured in such horrible conditions, but as consumers we must take
      responsibility for the well-being of these children. 

PMID- 24441694
TI  - Practicing prevention in the music schools.

PMID- 24441696
TI  - From the editor.

PMID- 24441695
TI  - Corrigendum to "Work-related musculoskeletal symptoms among construction workers
      in the pipe trades" [Work 7 (1996) 13-20].

PMID- 24441697
TI  - Industrial rehabilitation - deja vu.

PMID- 24441698
TI  - Preventing the IncurableProactive Risk Management.

PMID- 24441699
TI  - Applied ergonomics.

PMID- 24441700
TI  - Enlisting participation in an injury prevention and management program.

PMID- 24441701
TI  - Employment ScreeningLegal and Clinical Considerations.

PMID- 24441702
TI  - Hands at work.

PMID- 24441703
TI  - Beyond work hardening 101.

PMID- 24441704
TI  - The Impact of CARF Standards on the Practice of Work Hardening.

PMID- 24441705
TI  - Accountability problems and implications for the profession.

PMID- 24441707
TI  - Average and local atomic-scale structure in BaZrxTi(1-x)O3 (x = 0. 10, 0.20,
      0.40) ceramics by high-energy x-ray diffraction and Raman spectroscopy.
AB  - High-resolution x-ray diffraction (XRD), Raman spectroscopy and total scattering
      XRD coupled to atomic pair distribution function (PDF) analysis studies of the
      atomic-scale structure of archetypal BaZrxTi(1-x)O3 (x = 0.10, 0.20, 0.40)
      ceramics are presented over a wide temperature range (100-450 K). For x = 0.1 and
      0.2 the results reveal, well above the Curie temperature, the presence of Ti-rich
      polar clusters which are precursors of a long-range ferroelectric order observed
      below TC. Polar nanoregions (PNRs) and relaxor behaviour are observed over the
      whole temperature range for x = 0.4. Irrespective of ceramic composition, the
      polar clusters are due to locally correlated off-centre displacement of Zr/Ti
      cations compatible with local rhombohedral symmetry. Formation of Zr-rich
      clusters is indicated by Raman spectroscopy for all compositions. Considering the
      isovalent substitution of Ti with Zr in BaZrxTi1-xO3, the mechanism of formation
      and growth of the PNRs is not due to charge ordering and random fields, but
      rather to a reduction of the local strain promoted by the large difference in ion
      size between Zr(4+) and Ti(4+). As a result, non-polar or weakly polar Zr-rich
      clusters and polar Ti-rich clusters are randomly distributed in a paraelectric
      lattice and the long-range ferroelectric order is disrupted with increasing Zr
      concentration.

PMID- 24441709
TI  - Volatile composition and sensory properties of Indian herbal medicine-Pavonia
      odorata-used in Ayurveda.
AB  - The chemical composition of volatile oil obtained from aerial parts of Pavonia
      odorata were investigated using gas chromatography-mass spectrometry (GC-MS). Its
      aroma-active compounds were identified using gas chromatography-olfactometry (GC
      O) and aroma extraction dilution analysis (AEDA). In order to determine the
      relative contribution of each compound to the aroma of P. odorata, relative
      flavour activity (RFA) was calculated. The hydrodistillation of P. odorata
      afforded yellowish oil and the yield was 0.009% (w/w) with a spicy, sweet, and
      green odour. Eighty-five compounds were identified in the oil by GC-MS; the major
      constituents of the volatile oil were ageratochromene (11.95%), palmitic acid
      (9.95%), hexahydrofarnesyl acetone (5.96%), beta-eudesmol (4.53%) and beta
      caryophyllene oxide (3.08%). The most characteristic aroma compounds in the
      volatile oil were identified for beta-caryophyllene oxide (FD-factor = 128,
      spicy), (E)-pinocarveol (FD-factor = 64, sweet), 3-butylpyridine (FD-factor = 64,
      spicy), and 2-nonanone (FD-factor = 32, green) by GC-MS, GC-O and AEDA. It seems
      that these compounds are responsible for the spicy, sweet and green odour of the
      aerial parts of P. odorata. The antioxidant activity of the volatile oil was also
      investigated by the oxygen radical absorbance capacity (ORAC) assay using
      fluorescein (FL) as the fluorescent probe. The ORAC value of the oil was 594.2 +/
      25.9 MUM TE/g. The results indicated that the volatile oil from the aerial parts
      of P. odorata could be considered as a natural antioxidant effect agent. 

PMID- 24441708
TI  - Interaction between functionalized gold nanoparticles in physiological saline.
AB  - The interactions between functionalized noble-metal particles in an aqueous
      solution are central to applications relying on controlled equilibrium
      association. Herein, we obtain the potentials of mean force (PMF) for pair
      interactions between functionalized gold nanoparticles (AuNPs) in physiological
      saline. These results are based upon >1000 ns experiments in silico of all-atom
      model systems under equilibrium and non-equilibrium conditions. Four types of
      functionalization are built by coating each globular Au144 cluster with 60
      thiolate groups: GS-AuNP (glutathionate), PhS-AuNP (thiophenol), CyS-AuNP
      (cysteinyl), and p-APhS-AuNP (para-amino-thiophenol), which are, respectively,
      negatively charged, hydrophobic (neutral-nonpolar), hydrophilic (neutral-polar),
      and positively charged at neutral pH. The results confirm the behavior expected
      of neutral (hydrophilic or hydrophobic) particles in a dilute aqueous
      environment, however the PMF curves demonstrate that the charged AuNPs interact
      with one another in a unique way-mediated by H2O molecules and an electrolyte
      (Na(+), Cl(-))-in a physiological environment. In the case of two GS-AuNPs, the
      excess, neutralizing Na(+) ions form a mobile (or 'dynamic') cloud of enhanced
      concentration between the like-charged GS-AuNPs, inducing a moderate attraction
      (~25 kT) between them. Furthermore, to a lesser degree, for a pair of p-APhS
      AuNPs, the excess, neutralizing Cl(-) ions (less mobile than Na(+)) also form a
      cloud of higher concentration between the two like-charged p-APhS-AuNPs, inducing
      weaker yet significant attractions (~12 kT). On combining one GS- with one p-APhS
      AuNP, the direct, attractive Coulombic force is completely screened out while the
      solvation effects give rise to moderate repulsion between the two unlike-charged
      AuNPs. 

PMID- 24441710
TI  - Torpor in free-ranging antechinus: does it increase fitness?
AB  - Antechinus are small, insectivorous, heterothermic marsupial mammals that use
      torpor from late summer to early winter and reproduce once a year in late
      winter/early spring. Males die after mating, most females produce only a single
      litter, but some survive a second winter and produce another litter. As it is not
      known how these females manage to survive the second winter after the
      energetically demanding reproductive period and then reproduce a second time, we
      aimed to provide the first data on thermal biology of free-ranging antechinus by
      using temperature telemetry. Male Antechinus stuartii and Antechinus flavipes
      rarely entered torpor in autumn/early winter in the wild, expressing only shallow
      bouts of <2 h. Female A. stuartii used torpor extensively, employing bouts up to
      16.7 h with body temperatures as low as 17.8  degrees C. Interestingly, although
      first and second year females used similar torpor patterns, torpor occurrence was
      almost twofold in second year (93 % of days) than first year females (49 %), and
      the proportion of the overall monitoring period animals spent torpid was 3.2-fold
      longer in the former with a corresponding shorter activity period. Our study
      suggests that intensive use of torpor is crucial for second year females for
      autumn and winter survival and production of a second litter. We provide the
      first evidence of an age-related pattern in daily torpor expression in free
      ranging mammals and show that torpor use is a complex process that is affected
      not only by the current energy availability and thermal conditions but also by
      the reproductive history and age of individuals.

PMID- 24441711
TI  - Keratin decomposition by trogid beetles: evidence from a feeding experiment and
      stable isotope analysis.
AB  - The decomposition of vertebrate carcasses is an important ecosystem function.
      Soft tissues of dead vertebrates are rapidly decomposed by diverse animals.
      However, decomposition of hard tissues such as hairs and feathers is much slower
      because only a few animals can digest keratin, a protein that is concentrated in
      hairs and feathers. Although beetles of the family Trogidae are considered
      keratin feeders, their ecological function has rarely been explored. Here, we
      investigated the keratin-decomposition function of trogid beetles in heron
      breeding colonies where keratin was frequently supplied as feathers. Three trogid
      species were collected from the colonies and observed feeding on heron feathers
      under laboratory conditions. We also measured the nitrogen (delta(15)N) and
      carbon (delta(13)C) stable isotope ratios of two trogid species that were
      maintained on a constant diet (feathers from one heron individual) during 70 days
      under laboratory conditions. We compared the isotopic signatures of the trogids
      with the feathers to investigate isotopic shifts from the feathers to the
      consumers for delta(15)N and delta(13)C. We used mixing models (MixSIR and SIAR)
      to estimate the main diets of individual field-collected trogid beetles. The
      analysis indicated that heron feathers were more important as food for trogid
      beetles than were soft tissues under field conditions. Together, the feeding
      experiment and stable isotope analysis provided strong evidence of keratin
      decomposition by trogid beetles.

PMID- 24441712
TI  - Earliest and first Northern Hemispheric hoatzin fossils substantiate Old World
      origin of a "Neotropic endemic".
AB  - The recent identification of hoatzins (Opisthocomiformes) in the Miocene of
      Africa showed part of the evolution of these birds, which are now only found in
      South America, to have taken place outside the Neotropic region. Here, we
      describe a new fossil species from the late Eocene of France, which constitutes
      the earliest fossil record of hoatzins and the first one from the Northern
      Hemisphere. Protoazin parisiensis gen. et sp. nov. is more closely related to
      South American Opisthocomiformes than the African taxon Namibiavis and
      substantiates an Old World origin of hoatzins, as well as a relictual
      distribution of the single extant species. Although recognition of hoatzins in
      Europe may challenge their presumed transatlantic dispersal, there are still no
      North American fossils in support of an alternative, Northern Hemispheric,
      dispersal route. In addition to Opisthocomiformes, other avian taxa are known
      from the Cenozoic of Europe, the extant representatives of which are only found
      in South America. Recognition of hoatzins in the early Cenozoic of Europe is of
      particular significance because Opisthocomiformes have a fossil record in sub
      Saharan Africa, which supports the hypothesis that extinction of at least some of
      these "South American" groups outside the Neotropic region was not primarily due
      to climatic factors.

PMID- 24441713
TI  - Repair of Bochdalek hernia in an adult complicated by abdominal compartment
      syndrome, gastropleural fistula and pleural empyema: Report of a case.
AB  - INTRODUCTION: Bochdalek's diaphragmatic hernia (BDH) rarely developed symptomatic
      in adulthood but mostly required an operation. In adult BDH cases, long-term
      residing of the massive intraabdominal organs in the thoracic cavity passively
      causes loss of domain for abdominal organs (LOD). PRESENTATION OF CASE: A 63-year
      old man presented at our institution complaining of sudden left upper quadrant
      abdominal pain. Chest radiography showed a hyperdense lesion containing bowel gas
      in the left pleural space. Computed tomography revealed a dilated bowel above the
      diaphragm and intestinal obstruction suggestive of gangrenous changes. These
      findings were consistent with the diagnosis of incarcerated BDH and an emergency
      laparotomy was performed. Operative findings revealed the hypoplastic lung, lack
      of hernia sac, and location of the diaphragmatic defect, which indicated that his
      hernia was true congenital. Organs were reduced into the abdominal cavity, and
      large defect of the diaphragm was repaired with combination of direct vascular
      closure and intraperitoneal onlay mesh reinforcement using with expanded
      polytetrafluoroethylene (ePTFE) mesh. On the postoperative day 1, the patient
      fell into the shock and was diagnosed to have abdominal compartment syndrome
      (ACS). Conservative therapies were administered, but resulted in gastropleural
      fistula and pleural empyema, which required an emergency surgery. Mesh extraction
      and fistulectomy were performed. DISCUSSION: A PubMed search for the case of ACS
      after repair of the adult BDH revealed only three cases, making this very rare
      condition. CONCLUSION: In dealing with adult BDH, possible post-repair ACS should
      be considered.

PMID- 24441714
TI  - Does form follow function in trochlear dysplasia? Case report of patellar
      instability in a below-knee amputee.
AB  - INTRODUCTION: Patellar instability can be considered as a rapidly increasing
      musculoskeletal subject of interest. It is now well accepted that multiple
      factors can produce this pathological condition, isolated, but more often in
      concert. One major static compound is found to be in trochlear dysplasia. It has
      been stated that the form of the trochlear surface is primary and genetically
      bilaterally determined already before use. According to these data, recurrent
      dislocation of the patella has been described as a hereditary disease with
      autosomal dominant transmission. Against this assumption, we hypothesize that
      subjects may devise a flattened trochlea when there is no significant
      biomechanical interplay and thus input between the patella and the distal femur
      during developmental growth; according to the assumption form follows function.
      PRESENTATION OF CASE: In this context, we report the case of a 16-year old male
      who previously suffered from a traumatic patellar dislocation during sporting
      activity in his below-knee amputated lower extremity, which occured at age of 18
      months. The patient was allocated with a high-grade trochlear dysplasia in his
      previously amputated limb, while presenting a normal trochlear shape at his
      healthy contralateral leg. DISCUSSION: This rare case therefore reprents the
      history of an individuum with identic genetic predisposition and different
      biomechanical influences during childhood, which makes it of high clinical
      interest. In presence of trochlear dysplasia the patient suffered reluxation and
      concurrent subjective instability on the lower limb affected by the amputation
      which was treated with medial patellofemoral ligament (MPFL) plasty using an
      autologous gracilis graft. CONCLUSION: One has to consider that a certain
      biomechanical input may be required for the development of a physiologic
      trochlear groove.

PMID- 24441715
TI  - Removal of aberrant azygos lobe containing positron emission tomography positive
      nodule with the use of video-assisted thoracic surgery.
AB  - INTRODUCTION: The Azygos lobe is a well-known but rare variant of the lung. This
      case reports the use of video-assisted thoracic surgery to diagnose and treat
      presumptive lung cancer of the azygos lobe. PRESENTATION OF CASE: A 67-year old
      female with known severe Chronic Obstructive Pulmonary Disease presented with
      increasing shortness of breath. Chest x-ray revealed a lung nodule in the right
      lung field. PET/CT imaging delineated a 1.6x1.2cm speculated lesion in an
      aberrant azygos lobe. After appropriate preoperative testing and evaluation, the
      patient was taken to the operating room where the azygos lobe was removed using
      video-assisted thoracic surgery. DISCUSSION: The Azygos lobe is a well-known
      anatomical variant but such a lobe is rarely found to contain a malignant lesion.
      Azygos lobe removal alone may not be the best therapeutic option given the risk
      of locally recurrent disease, but in a select group of patients such as those
      with impaired lung function as this article describes, it may be the best
      available option in order to preserve postoperative pulmonary function.
      CONCLUSION: This case illustrates that gentle caudal traction on the azygos lobe
      will allow circumferential exposure to the lobe and identification of the
      bronchovascular pedicle thereby eliminating the need for thoracotomy and or
      extensive azygos vein dissection/division.

PMID- 24441716
TI  - Giant rectal villous adenoma: Surgical approach with rectal eversion and perianal
      coloanal anastomosis.
AB  - INTRODUCTION: Colorectal cancer is an important cause of death. Most cases of
      colon and rectal cancer arise from a preexisting adenomatous polyp. However, if
      colorectal polyps are very large or not accessible for endoscopic ablation, or if
      they cannot be removed without an increased risk of perforation, surgical
      procedures are required. PRESENTATION OF CASE: The case of a patient with a giant
      villous adenoma of the rectum is described. The patient had diarrhea for 2 years
      associated with asthenia. Colonoscopy revealed a sessile lesion in the rectum
      measuring 14cm in the largest diameter. Rectal eversion technique was used,
      resecting the lesion under direct visibility and an external coloanal anastomosis
      was performed. Surgery was satisfactory and the resection margins were free.
      DISCUSSION: Removal of these polyps should be performed aiming to reduce the
      incidence of colorectal cancer, as well as to control local and systemic
      symptoms, such as diarrhea and fluid and electrolyte disorders, mainly in villous
      adenomas. Various surgical techniques are proposed, but in extensive
      circumferential lesions of the rectum they are difficult to apply. The rectal
      stump eversion technique was described by Maunsell (1892), for rectal cancer.
      CONCLUSION: Eversion of the rectal stump and external coloanal anastomosis may be
      a good surgical alternative for resecting giant rectal adenomas.

PMID- 24441718
TI  - Mathematical modeling of patient-specific ventricular assist device implantation
      to reduce particulate embolization rate to cerebral vessels.
AB  - Stroke is the most devastating complication after ventricular assist device (VAD)
      implantation, with an incidence of 14%-47% despite improvements in device design
      and anticoagulation. This complication continues to limit the widespread
      implementation of VAD therapy. Patient-specific computational fluid dynamics
      (CFD) analysis may elucidate ways to reduce this risk. A patient-specific three
      dimensional model of the aortic arch was generated from computed tomography. A 12
      mm VAD outflow-graft (VAD-OG) "anastomosed" to the aorta was rendered. CFD was
      applied to study blood flow patterns. Particle tracks, originating from the VAD,
      were computed with a Lagrangian phase model and percentage of particles entering
      the cerebral vessels was calculated. Twelve implantation configurations of the
      VAD-OG and three particle sizes (2, 4, and 5 mm) were considered. Percentage of
      particles entering the cerebral vessels ranged from 6% for the descending aorta
      VAD-OG anastomosis, to 14% for the ascending aorta at 90 deg VAD-OG anastomosis.
      Values were significantly different among all configurations (X(2) = 3925, p <
      0.0001). Shallower and more cephalad anastomoses prevented formation of zones of
      recirculation in the ascending aorta. In this computational model and within the
      range of anatomic parameters considered, the percentage of particles entering the
      cerebral vessels from a VAD-OG is reduced by nearly 60% by optimizing outflow
      graft configuration. Ascending aorta recirculation zones, which may be
      thrombogenic, can also be eliminated. CFD methods coupled with patient-specific
      anatomy may aid in identifying the optimal location and angle for VAD-OG
      anastomosis to minimize stroke risk.

PMID- 24441717
TI  - Asiatic acid alleviates hemodynamic and metabolic alterations via restoring
      eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced
      metabolic syndrome rats.
AB  - Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study
      aimed to investigate whether asiatic acid could lessen the metabolic,
      cardiovascular complications in rats with metabolic syndrome (MS) induced by a
      high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with
      HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats
      were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further
      three weeks. MS rats had an impairment of oral glucose tolerance, increases in
      fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean
      arterial blood pressure, heart rate, and hindlimb vascular resistance; these were
      related to the augmentation of vascular superoxide anion production, plasma
      malondialdehyde and tumor necrosis factor-alpha (TNF-alpha) levels (p<0.05).
      Plasma nitrate and nitrite (NOx) were markedly high with upregulation of
      inducible nitric oxide synthase (iNOS) expression, but dowregulation of
      endothelial nitric oxide synthase (eNOS) expression (p<0.05). Asiatic acid
      significantly improved insulin sensitivity, lipid profiles, hemodynamic
      parameters, oxidative stress markers, plasma TNF-alpha, NOx, and recovered
      abnormality of eNOS/iNOS expressions in MS rats (p<0.05). In conclusion, asiatic
      acid improved metabolic, hemodynamic abnormalities in MS rats that could be
      associated with its antioxidant, anti-inflammatory effects and recovering
      regulation of eNOS/iNOS expression.

PMID- 24441719
TI  - From the editor.

PMID- 24441720
TI  - Work for psychiatrically disabled clients.

PMID- 24441721
TI  - Vocational programming for adolescents with psychiatric impairments.

PMID- 24441722
TI  - A Supported Employment Enclave Model for the Psychiatrically ChallengedA Program
      Critique.

PMID- 24441723
TI  - Chronic Musculoskeletal PainPsychological Strategies for Rehabilitation in an
      Interdisciplinary Setting.

PMID- 24441724
TI  - Psychiatric DisorderEffects on Rehabilitation and Ability to Return to Work.

PMID- 24441725
TI  - Developmental Disabilities and Long-Term Mental IllnessNew Work Programs.

PMID- 24441726
TI  - Occupational stress and the depressed female client.

PMID- 24441727
TI  - Work Programming for Psychiatric ClientsAn Interdisciplinary Approach.

PMID- 24441728
TI  - Work programming with geriatric mental health clients.

PMID- 24441729
TI  - Practice burdens or responsibilities?
AB  - Most of us hold opinions on contemporary issues in work practice, in all its
      broad dimensions. Sounding Board is a regular feature of this publication,
      designed to provide a forum for expressing such views, whether mainstream or
      controversial.The opinions expressed in this section may not necessarily
      represent the views of the editor, the publisher, or the editorial board, but are
      intended to stimulate discussion or to provoke a response. Readers who wish to
      comment on the ideas put forth in Sounding Board should address their comments to
      the editor. 

PMID- 24441731
TI  - Spatial and decadal variations in inorganic nitrogen wet deposition in China
      induced by human activity.
AB  - Atmospheric nitrogen (N) deposition, an important component in the global N
      cycle, has increased sharply in recent decades in China. Here, we constructed
      national-scale inorganic N wet deposition (Ndep) patterns in China based on data
      from 280 observational sites and analysed the effects of anthropogenic sources
      and precipitation on Ndep. Our results showed that the mean Ndep over China
      increased approximately 25%, from 11.11 kg ha(-1) a(-1) in the 1990s to 13.87 in
      the 2000s. Ndep was highest over southern China and exhibited a decreasing
      gradient from southern to western and northern China. The decadal difference in
      Ndep between the 1990s and 2000s was primarily caused by increases in energy
      consumption and N fertiliser use. Our findings conformed that anthropogenic
      activities were the main reason for the Ndep increase and provide a scientific
      background for studies on ecological effects of N deposition in China. 

PMID- 24441732
TI  - Computer-assisted navigation in ACL reconstruction is attractive but not yet cost
      efficient.
AB  - PURPOSE: Conventional reconstruction of the anterior cruciate ligament (ACL) has
      a high success rate. Computer-assisted navigation systems (CANSs) have been
      developed to further improve the accuracy of tunnel positioning. What is the
      economic impact from the hospital perspective? METHODS: Patients having a first
      ACL reconstruction procedure were included in a prospective multicentre open
      controlled study comparing two groups: CANS versus conventional surgery. The
      primary clinical efficacy criterion was the objective International Knee
      Documentation Committee score at 1-2-year follow-up. Costs were collected
      retrospectively nationwide. RESULTS: No significant differences were found for
      the clinical effectiveness between conventional surgery (100 patients) and CANS
      (114 patients) at follow-up: ORadjusted 1.01 [0.36-2.84] (n.s). Junior surgeons
      achieved a significant mean decrease in operating time during the study period:
      30 % in the CANS group compared with 10 % in the control group (p < 0.01). The
      average cost of surgery was 704<euro> for the control group and 1,158<euro> for
      the CANS group (p < 0.01). The cost of the operating room accounts for >70 % of
      the total cost. The surgeon's status and the technical CANS learning effect
      influenced this cost. The cost differential between the two groups decreased with
      'CANS' expertise: 238<euro> and 271<euro> in 'expert' centres versus 427<euro> to
      731<euro> in other centres. CONCLUSION: While our study demonstrates the
      feasibility and the potential interest of CANS for training in ACL
      reconstruction, from a hospital perspective it is not cost efficient at present.
      LEVEL OF EVIDENCE: Economic and decision analysis-developing an economic or
      decision model, Level II.

PMID- 24441733
TI  - The combined Whiteside's and posterior condylar line as a reliable reference to
      describe axial distal femoral anatomy in patient-specific instrument planning.
AB  - PURPOSE: Aligning the femoral component in the axial plane parallel to the
      surgical epicondylar axis (SEA) has been generally recommended. In this
      retrospective study on the axial anatomy of the distal femur, as determined by
      the patient-specific instruments (PSI) planning tool based on MRI and 3D
      reconstructions, the different rotational axes were compared. The purpose of this
      study was to compare the impact of posterior axial anatomy on anterior anatomy
      and to compare the different angles of rotation obtained by a PSI-planning
      engineer. METHODS: The preoperative planning of 77 PSI patients with a mean (SD)
      age of 65.6 (9.6) years undergoing primary total knee replacement for
      osteoarthritis was analysed for rotational anatomy of the distal femur. The
      angles between the posterior condylar line (PCL) and the SEA called posterior
      condylar angle (PCA), between Whiteside's line and the SEA and finally between
      Whiteside's line and the PCL, were retrieved from the PSI axial rotation planning
      screen. RESULTS: The mean (SD) PCA was 3.2 degrees  (1.4 degrees ). The mean (SD)
      angle between Whiteside's line and the SEA was 91.4 degrees  (2.2 degrees ), and
      the mean (SD) angle between Whiteside's line and the PCL was 94.5 degrees  (2.3
      degrees ). No significant difference for this last rotational parameter was found
      in between varus and valgus knees. CONCLUSION: Patient-specific instrument's
      preoperative planning found consistent angles to describe the distal femoral
      anatomy as previously published in the literature. The angle between Whiteside's
      line and the PCL as measured on PSI planning is a mean angle of 94.5 degrees 
      (2.3 degrees ) for both varus and valgus knees. Setting a fixed PCA of 5 degrees 
      of external rotation referenced of the PCL makes this planning repeatable during
      conventional surgery. LEVEL OF EVIDENCE: Therapeutic study, Level III.

PMID- 24441734
TI  - Microfracture technique versus osteochondral autologous transplantation
      mosaicplasty in patients with articular chondral lesions of the knee: a
      prospective randomized trial with long-term follow-up.
AB  - PURPOSE: To compare long-term functional and radiological outcome following
      microfracture technique (MF) versus osteochondral autologous transplantation
      (OAT) mosaicplasty for treating focal chondral lesions of the knee. METHODS:
      Twenty-five patients (mean age 32.3 years, SD 7.7) with a full-thickness
      (International Cartilage Repair Society grade 3 or 4) chondral lesion of the
      articulating surface of the femur were randomized to either MF (n = 11) or OAT
      mosaicplasty (n = 14). At a median follow-up of 9.8 years (range 4.9-11.4), the
      patients were evaluated using Lysholm score (n = 25), Knee Injury and
      Osteoarthritis Outcome Score (KOOS, n = 25), isokinetic quadriceps measurement
      and hamstring strength measurement (n = 22) and standing radiographs (n = 23).
      RESULTS: There were no significant differences in Lysholm score, KOOS, isokinetic
      muscle strength or radiographic osteoarthritis between MF-treated patients and
      OAT mosaicplasty-treated patients at follow-up. Mean Lysholm score at follow-up
      was 69.7 [95% confidence interval (CI), 55.1-84.4] for the MF group and 62.6 (95%
      CI, 52.6-72.6) for the OAT mosaicplasty group. CONCLUSION: At long-term follow
      up, there were no significant differences between patients treated with MF and
      patients treated with OAT mosaicplasty in patient-reported outcomes, muscle
      strength or radiological outcome. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 24441735
TI  - Topographical control of multiple cell adhesion molecules for traction force
      microscopy.
AB  - Cellular traction forces are important quantitative measures in cell biology as
      they have provided much insight into cell behavior in contexts such as cellular
      migration, differentiation, and disease progression. However, the complex
      environment in vivo permits application of cell traction forces through multiple
      types of cell adhesion molecules. Currently available approaches to differentiate
      traction forces among multiple cell adhesion molecules are limited to specialized
      approaches to decouple cell-cell from cell-extracellular matrix (ECM) tractions.
      Here, we present a technique which uses indirect micropatterning onto a
      polyacrylamide gel to pattern multiple, spatially distinct fluorescently labeled
      ECM proteins, specifically gelatin and fibronectin (Fn), and confine the area to
      which cells can adhere. We found that cells interacting with both gelatin and Fn
      altered their traction forces significantly in comparison to cells on Fn-only
      substrates. This crosstalk interaction resulted in a decrease in overall traction
      forces on dual-patterned substrates as compared to cells on Fn-only substrates.
      This illustrates the unique need to study such interactions and demonstrates
      great potential in future studies in multi-ligand environments. Current
      micropatterning techniques on glass can easily be adapted to present other
      protein classes, such as cadherins, while maintaining control of adhesion
      spacing, cell spread area, and stiffness, each of which are important regulators
      of cell mechanobiology. 

PMID- 24441738
TI  - Rotation of the eyes (not the head) potentiates the postauricular muscle
      response.
AB  - OBJECTIVE: The authors investigated how eye and head rotation modulate the human
      postauricular muscle response (PAMR), to determine the optimal strategy for
      potentiating the PAMR, or minimizing it to reduce contamination of small
      neurogenic responses. DESIGN: The authors recorded the PAMR evoked by binaural
      bipolar clicks (50 dB SL, 360 usec per phase with 53-msec interval) from behind
      the right ear of 12 normally hearing adults, and attempted to enhance it with (a)
      voluntary ear contraction alone, (b) head rotation alone (with the eyes forward
      directed and tracking a target attached to the head), or (c) by lateral eye
      movement alone (toward the right measurement side, with the head facing forward).
      RESULTS: When the head alone was rotated with eyes fixed relative to the head,
      the PAMR increased only slightly in some subjects, as did the ongoing
      electromyography (EMG) (probably due to EMG activity from nearby neck muscles).
      On returning the head to the forward control position, the PAMR dropped rapidly
      to control amplitudes. When the eyes alone were rotated, both the EMG and the
      PAMR increased markedly in most subjects, and returning the eyes to their control
      position produced a gradual return to control amplitudes. Voluntary PAM
      contraction (in those subjects who could accomplish it) increased the EMG tone
      and the PAMR amplitude concomitantly, with vigorous voluntary PAM contraction
      saturating the PAMR but not the EMG. CONCLUSION: Head rotation alone was not
      effective in potentiating the PAMR when lateral eye movement relative to the head
      was avoided during the head rotation maneuver. When lateral eye movement was
      controlled appropriately, the PAMR could be potentiated reliably, or reliably
      avoided when recording smaller neurogenic responses. If head rotation was used to
      optimize the PAMR without explicit control of eye movement, a false impression of
      variability was produced.

PMID- 24441736
TI  - Genome sequence of the hot pepper provides insights into the evolution of
      pungency in Capsicum species.
AB  - Hot pepper (Capsicum annuum), one of the oldest domesticated crops in the
      Americas, is the most widely grown spice crop in the world. We report whole
      genome sequencing and assembly of the hot pepper (Mexican landrace of Capsicum
      annuum cv. CM334) at 186.6* coverage. We also report resequencing of two
      cultivated peppers and de novo sequencing of the wild species Capsicum chinense.
      The genome size of the hot pepper was approximately fourfold larger than that of
      its close relative tomato, and the genome showed an accumulation of Gypsy and
      Caulimoviridae family elements. Integrative genomic and transcriptomic analyses
      suggested that change in gene expression and neofunctionalization of capsaicin
      synthase have shaped capsaicinoid biosynthesis. We found differential molecular
      patterns of ripening regulators and ethylene synthesis in hot pepper and tomato.
      The reference genome will serve as a platform for improving the nutritional and
      medicinal values of Capsicum species. 

PMID- 24441739
TI  - Effects of age on melody and timbre perception in simulations of electro-acoustic
      and cochlear-implant hearing.
AB  - OBJECTIVES: Recent evidence suggests that age might affect the ability of
      listeners to process fundamental frequency cues in speech, and that this
      difficulty might impact the ability of older listeners to use and combine
      envelope and fine structure cues available in simulations of electro-acoustic and
      cochlear-implant hearing. The purpose of this article is to examine whether this
      difficulty extends to music. Specially, this study focuses on whether older
      listeners have a decreased ability to use and combine different types of cues in
      the perception of melody and timbre. DESIGN: A group of older listeners with
      normal to near-normal hearing and a group of younger listeners with normal
      hearing participated in the melody and timbre recognition tasks of the University
      of Washington Clinical Assessment of Music Perception test. The recognition tasks
      were completed for five different processing conditions: (1) an unprocessed
      condition; (2) an eight-channel vocoding condition that simulated a traditional
      cochlear implant and contained temporal envelope cues; (3) a simulation of
      electro-acoustic stimulation (sEAS) that included a low-pass acoustic component
      and high-pass vocoded portion, and which provided fine structure and envelope
      cues; (4) a condition that included only the low-pass acoustic portion of the
      sEAS; and (5) a condition that included only the high-frequency vocoded portion
      of the sEAS stimulus. RESULTS: Melody recognition was excellent for both younger
      and older listeners in the conditions containing the unprocessed stimuli, the
      full sEAS stimuli, and the low-pass sEAS stimuli. Melody recognition was
      significantly worse in the cochlear-implant simulation condition, especially for
      the older group of listeners. Performance on the timbre task was highest for the
      unprocessed condition, and progressively decreased for the sEAS and cochlear
      implant simulation conditions. Compared with younger listeners, older listeners
      had significantly poorer timbre recognition for all processing conditions. For
      melody recognition, the unprocessed low-frequency portion of the sEAS stimulus
      was the primary factor determining improved performance in the sEAS condition
      compared with the cochlear-implant simulation. For timbre recognition, both the
      unprocessed low-frequency and high-frequency vocoded portions of the sEAS
      stimulus contributed to sEAS improvement in the younger group. In contrast, most
      listeners in the older group were not able to take advantage of the high
      frequency vocoded portion of the sEAS stimulus for timbre recognition.
      CONCLUSIONS: The results of this simulation study support the idea that older
      listeners will have diminished timbre and melody perception in traditional
      cochlear-implant listening due to degraded envelope processing. The findings also
      suggest that music perception by older listeners with cochlear implants will be
      improved with the addition of low-frequency residual hearing. However, these
      improvements might not be comparable for all dimensions of music perception. That
      is, more improvement might be evident for tasks that rely primarily on the low
      frequency portion of the electro-acoustic stimulus (e.g., melody recognition),
      and less improvement might be evident in situations that require across-frequency
      integration of cues (e.g., timbre perception).

PMID- 24441737
TI  - Genome of the human hookworm Necator americanus.
AB  - The hookworm Necator americanus is the predominant soil-transmitted human
      parasite. Adult worms feed on blood in the small intestine, causing iron
      deficiency anemia, malnutrition, growth and development stunting in children, and
      severe morbidity and mortality during pregnancy in women. We report sequencing
      and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization
      of this first hookworm genome sequence identified genes orchestrating the
      hookworm's invasion of the human host, genes involved in blood feeding and
      development, and genes encoding proteins that represent new potential drug
      targets against hookworms. N. americanus has undergone a considerable and unique
      expansion of immunomodulator proteins, some of which we highlight as potential
      treatments against inflammatory diseases. We also used a protein microarray to
      demonstrate a postgenomic application of the hookworm genome sequence. This
      genome provides an invaluable resource to boost ongoing efforts toward
      fundamental and applied postgenomic research, including the development of new
      methods to control hookworm and human immunological diseases. 

PMID- 24441741
TI  - A comparison of auditory brain stem responses elicited by click and chirp stimuli
      in adults with normal hearing and sensory hearing loss.
AB  - OBJECTIVES: The aim of this study was to compare the human auditory brain stem
      response (ABR) elicited by clicks and chirps with overall behavioral hearing
      thresholds in participants with normal hearing and with sensory hearing loss. The
      authors hypothesized that ABRs to chirps would be more robust and that thresholds
      would be more similar to overall behavioral hearing thresholds compared with ABRs
      to clicks. DESIGN: Twenty-five adults with normal hearing and 25 adults with
      sensory hearing loss were recruited. Subjects were without middle ear or
      neurological pathologies at the time of testing. Subjects with sensory hearing
      loss were separated into mild to moderate hearing loss and mild to severe hearing
      loss groups. Behavioral hearing thresholds for pure tones were obtained at nine
      octave and interoctave frequencies ranging from 250 to 8000 Hz; an average of
      these nine frequencies was calculated for each participant. Evoked potential
      thresholds were measured by ABRs to click and chirp stimuli. Analyses included
      wave V absolute latencies and wave V peak-to-peak amplitudes. Thresholds for ABRs
      to clicks and chirps were compared with each other and with overall behavioral
      hearing thresholds. RESULTS: ABR thresholds to chirp and click stimuli did not
      differ significantly for either the normal-hearing or the hearing loss groups.
      Wave V peak-to-peak amplitude was higher for chirps than clicks, particularly at
      lower intensities, for all groups. ABR thresholds to chirps were closer to
      overall behavioral thresholds than clicks in all groups. Moreover, ABR thresholds
      to chirps did not differ significantly from behavioral thresholds in the two
      hearing loss groups. CONCLUSIONS: ABRs obtained with chirp stimuli provide an
      efficient method for estimating hearing thresholds in individuals with normal
      hearing and sensory hearing loss where broadband signals are selected for
      testing. ABRs to chirps display higher peak-to-peak amplitudes than those
      obtained with clicks and may provide responses closer to behavioral thresholds.
      This information could result in improved accuracy in identifying hearing loss
      and estimating hearing sensitivity for broadband signals in infants, children,
      and difficult-to-test older populations.

PMID- 24441740
TI  - Linguistic input, electronic media, and communication outcomes of toddlers with
      hearing loss.
AB  - OBJECTIVES: The objectives of this study were to examine the quantity of adult
      words, adult-child conversational turns, and electronic media in the auditory
      environments of toddlers who are hard of hearing (HH) and to examine whether
      these factors contributed to variability in children's communication outcomes.
      DESIGN: Participants were 28 children with mild to severe hearing loss. Full-day
      recordings of children's auditory environments were collected within 6 months of
      their second birthdays by using Language ENvironment Analysis technology. The
      system analyzes full-day acoustic recordings, yielding estimates of the quantity
      of adult words, conversational turns, and electronic media exposure in the
      recordings. Children's communication outcomes were assessed via the receptive and
      expressive scales of the Mullen Scales of Early Learning at 2 years of age and
      the Comprehensive Assessment of Spoken Language at 3 years of age. RESULTS: On
      average, the HH toddlers were exposed to approximately 1400 adult words per hour
      and participated in approximately 60 conversational turns per hour. An average of
      8% of each recording was classified as electronic media. However, there was
      considerable within-group variability on all three measures. Frequency of
      conversational turns, but not adult words, was positively associated with
      children's communication outcomes at 2 and 3 years of age. Amount of electronic
      media exposure was negatively associated with 2-year-old receptive language
      abilities; however, regression results indicate that the relationship was fully
      mediated by the quantity of conversational turns. CONCLUSIONS: HH toddlers who
      were engaged in more conversational turns demonstrated stronger linguistic
      outcomes than HH toddlers who were engaged in fewer conversational turns. The
      frequency of these interactions was found to be decreased in households with high
      rates of electronic media exposure. Optimal language-learning environments for HH
      toddlers include frequent linguistic interactions between parents and children.
      To support this goal, parents should be encouraged to reduce their children's
      exposure to electronic media.

PMID- 24441743
TI  - Sorafenib for patients with pretreated recurrent or progressive high-grade
      glioma: a retrospective, single-institution study.
AB  - Therapeutic options for patients with pretreated advanced high-grade glioma (HGG)
      are limited. Sorafenib, a small molecule with multiple potential beneficial
      actions, appears particularly promising. We reviewed the outcomes of 30 patients
      with recurrent or progressive HGG treated with sorafenib within a named patient
      program. Overall, 16 patients suffered from recurrent or progressive glioblastoma
      multiforme and 14 patients had grade 3 gliomas. All but four patients had
      previously undergone surgical debulking; all but one patient had received
      previous standard multimodal treatment; and 18 patients (60%) had received more
      than one line of chemotherapy, in median three. Progression-free survival (PFS),
      defined as the time from initiation of sorafenib to treatment discontinuation
      because of tumor progression or death, was selected as the endpoint. The use of
      sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9
      4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4-4.8
      months) in patients with other HGG. The PFS-6 for the whole cohort was 23%.
      Sixteen patients reported adverse events, mostly moderate, with hypertension as
      the most frequently reported toxicity (seven patients). One patient died of
      cerebral bleeding (grade 5 toxicity). The overall survival after initiation of
      sorafenib was 6 months (95% CI 3.9-8.0 months) for patients with glioblastoma
      multiforme and 10 months (95% CI 3.1-16.9 months) for patients with HGG. In this
      retrospective analysis of heavily pretreated patients with HGG, sorafenib
      monotherapy was associated with tumor stabilization in a small subset of
      patients. The risk-benefit ratio was acceptable in the context of an apparent
      clinical benefit in patients with a fatal disease. 

PMID- 24441742
TI  - Auditory impairments in HIV-infected individuals in Tanzania.
AB  - OBJECTIVES: Abnormal hearing tests have been noted in human immunodeficiency
      virus (HIV)-infected patients in several studies, but the nature of the hearing
      deficit has not been clearly defined. The authors performed a cross-sectional
      study of both HIV+ and HIV- individuals in Tanzania by using an audiological test
      battery. The authors hypothesized that HIV+ adults would have a higher prevalence
      of abnormal central and peripheral hearing test results compared with HIV-
      controls. In addition, they anticipated that the prevalence of abnormal hearing
      assessments would increase with antiretroviral therapy (ART) use and treatment
      for tuberculosis (TB). DESIGN: Pure-tone thresholds, distortion product
      otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were
      performed using a laptop-based hearing testing system on 751 subjects (100 HIV-
      in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+
      [130 ART- and 319 ART+], and 202 HIV-, subjects. No U.S. subjects had a history
      of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV- subjects had a
      history of TB treatment. Subjects completed a video and audio questionnaire about
      their hearing, as well as a health history questionnaire. RESULTS: HIV+ subjects
      had reduced DPOAE levels compared with HIV- subjects, but their hearing
      thresholds, tympanometry results, and gap-detection thresholds were similar.
      Within the HIV+ group, those on ART reported significantly greater difficulties
      understanding speech in noise, and were significantly more likely to report that
      they had difficulty understanding speech than the ART- group. The ART+ group had
      a significantly higher mean gap-detection threshold compared with the ART- group.
      No effects of TB treatment were seen. CONCLUSIONS: The fact that the ART+/ART-
      groups did not differ in measures of peripheral hearing ability (DPOAEs,
      thresholds), or middle ear measures (tympanometry), but that the ART+ group had
      significantly more trouble understanding speech and had higher gap-detection
      thresholds indicates a central processing deficit. These data suggest that: (1)
      hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection,
      (2) certain ART regimens might produce CNS side effects that manifest themselves
      as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV
      inadequately, perhaps due to insufficient CNS drug levels, which is reflected as
      a central hearing deficit. Monitoring of central hearing parameters could be used
      to track central effects of either HIV or ART.

PMID- 24441744
TI  - Cytotoxicity of lipophilic statins depends on their combined actions on HIF
      1alpha expression and redox status in B16.F10 melanoma cells.
AB  - Statins, as inhibitors of de-novo synthesis of cholesterol, exert cytotoxic
      actions on tumor cells. Despite the increasing data on the antitumoral activities
      of statins, their complete mechanisms of action still remain obscure. Therefore,
      the present study aims to investigate the mechanisms of lipophilic statin-induced
      cytotoxicity on B16.F10 murine melanoma cells in vitro. In-vitro effects of two
      lipophilic statins, simvastatin and lovastatin, and a hydrophilic statin,
      pravastatin, were investigated with respect to B16.F10 murine melanoma cell
      proliferation and viability. Our results show that only lipophilic statins
      exerted strong cytotoxic effects on B16.F10 melanoma cells. To gain further
      evidence on the pleiotropic effects of statins responsible for their cytotoxicity
      in B16.F10 cells, we have assessed their proapoptotic effects by Annexin V
      fluorescein isothiocyanate/propidium iodide staining and measured tumor cell
      production of the hypoxia-inducible factor 1alpha by western blot analysis,
      nonenzymatic antioxidant levels by an antioxidant colorimetric assay, and
      superoxide dismutase activity through an indirect method on the basis of
      inhibition of xanthine oxidase activity. Protein array was also used to assess
      angiogenic/inflammatory protein production in B16.F10 cells. Our results pointed
      out that the cytotoxic actions exerted by lipophilic statins were mainly based on
      the suppressive actions of these drugs on hypoxia-inducible factor 1alpha
      expression and nonenzymatic antioxidant levels, as well as because of the
      inhibition of superoxide dismutase activity in B16.F10 melanoma cells. In
      addition, the reduction in the angiogenic/inflammatory capacity of tumor cells
      induced by lipophilic statins can strengthen and support their cytotoxicity. 

PMID- 24441746
TI  - From the editor.

PMID- 24441747
TI  - Comparisons of wrist postures in VDT operators using wrist rests and forearm
      supports.
AB  - OBJECTIVE: The purpose of this study was to examine wrist motions in video
      display terminal (VDT) workers using the Greenleaf Medical WristSystem. This
      study was developed because of the limited research about the effectiveness of
      ergonomic equipment for VDT operators, as well as the recent increase in
      cumulative trauma disorders (CTDs) among these workers. STUDY DESIGN: Twenty
      adult VDT operators with no history of CTD were recruited from Boston University
      and surrounding businesses. WristSensorTM gloves containing dual-axis sensors for
      detection of dynamic wrist movements were worn by participants. Calibrations were
      then performed through the Movement Analysis System (MAS) software, after which
      participants were requested to type using a wrist rest (condition A), using
      forearm supports (condition B), using the wrist rest and forearm supports
      together (condition C), and finally using no form of wrist or forearm support
      (condition D). It was assumed by the investigators that wrist extension and ulnar
      deviation would decrease when using the wrist rest or forearm support, with the
      greatest change occurring when using both types of support. Questionnaires
      requesting demographic information were completed by each participant. Contrast
      scores were also calculated and converted into t -tests and their corresponding P
      -values. RESULTS: The average degrees of motion for both right and left hands
      were: flexion 4.5 degrees , extension 18.9 degrees , ulnar deviation 15.3 degrees
      , and radial deviation 2.0 degrees . P-values for all four conditions in the left
      hand were found to be significant and are as follows: extension t(19) = 2.35, P <
      0.025, flexion t(19) = 2.17, P < 0.025, ulnar deviation t(19) = 3.41, P < 0.0025,
      and radial deviation t(19) = 2.5, P < 0.025. The only significant P-value in the
      right hand was during ulnar deviation: t(19) = 2.7, P < 0.01. DISCUSSION:
      Research suggests that wrist extension greater than 15 degrees  and ulnar
      deviation greater than 20 degrees  can be predisposing factors to the development
      of CTDs. In this study, all four wrist motions remained under 20 degrees  during
      the three conditions using the wrist rest and forearm supports. A trend of
      continued decreases in ulnar deviation and wrist extension from using no supports
      to that requiring both types of supports was also observed. Specifically, the
      smallest degree of wrist extension appeared when participants used only the wrist
      rest; ulnar deviation was smallest when both supports were used. Right hand
      degree values were found to be generally larger than those for the left hand. It
      is hoped that these results can serve as a foundation for future investigation
      into the effectiveness of wrist and forearm supports in reducing CTDs.

PMID- 24441745
TI  - A small molecule, MTBT, prevents cancer cell growth by activating p38 MAPK.
AB  - Cancer is a disease of unscheduled cell division and many anticancer drugs target
      the cell cycle to inhibit the proliferation of cancer cells. We conducted a
      screen for new anticancer drugs that induce cell cycle arrest using a small
      compound library. From this screen, we identified 2-(3-methyl-thiophen-2-yl)-4
      (3,4-dioxybenzene) thiazole (MTBT), which causes accumulation of cancer cells
      with 4N DNA content and inhibits colony formation of several cancer cell lines.
      We further showed that the treatment of cancer cells with this compound for a
      longer time period leads to apoptosis, as indicated by the presence of cells with
      a sub-G1 peak and the appearance apoptotic markers. The increased phosphorylation
      of serine 10 on histone H3 in MTBT-treated cancer cells suggests cell cycle
      arrest in the M-phase. Strikingly, MTBT-induced cell cycle arrest and enhanced H3
      (Ser10) phosphorylation are abrogated by the pretreatment with SB203580, a
      specific inhibitor of mitogen-activated protein kinase p38. Moreover, treatment
      of cancer cells with MTBT induces the phosphorylation of p38, indicative of p38
      activation. Together, we have identified a new compound that inhibits cancer cell
      proliferation, which is likely a consequence of p38 activation. 

PMID- 24441748
TI  - Rehabilitation in the New Zealand logging industry.
AB  - Work within the New Zealand logging industry is recognised as being dangerous and
      physically demanding, with relatively high accident and injury frequency rates.
      As a consequence, the financial cost of accidents to the New Zealand Accident
      Rehabilitation and Compensation Insurance Corporation (ACC), and ultimately the
      logging industry, is extremely high. One method of reducing this cost is to
      achieve an early return to work through the use of rehabilitation techniques.
      Some rehabilitation techniques are already being used by logging and
      transportation contractors; these could be increased and diversified with help
      from the ACC (the New Zealand injury insurance scheme) which currently offers a
      variety of rehabilitation options. This report presents a number of contractor
      and worker initiated rehabilitation case studies, as well as two examples of how
      the ACC can provide financial assistance to achieve an early return to work. 

PMID- 24441749
TI  - Normative data for the Work BOXTM: females ages 20-49.
AB  - The purpose of this project was to continue the development of the Work boxTM
      following three studies to standardize instructions and determine test-retest
      reliability. Normative data were collected from 118 non-disabled female subjects
      between the ages of 20 and 49 years. Means, standard deviations, and ranges of
      performance for 5-year-age intervals were calculated and reported for assembly
      time, disassembly time, and total test time. Analysis of the data indicates a
      minor, though not significant, decline in test performance with increasing age
      and great variability in completion times overall. 

PMID- 24441750
TI  - Vocational rehabilitation services in the United Kingdom.
AB  - This paper reviews the way in which vocational rehabilitation services have
      evolved in the United Kingdom during the last 50 years, since the end of the
      Second World War. The services have changed in many ways since then but their
      overall structure and the aims set for them are still strongly influenced by the
      perceived needs of ex-servicemen, as embodied in the 1944 Disabled Persons Act.
      This Act provided the basis for a Quota Scheme and for the development of
      rehabilitation and placement services and of sheltered workshops. The paper
      outlines how each of these have evolved in three decades up until 1980 and then
      examines in a little more detail how somewhat more radical changes were
      introduced in the eighties and nineties. It concludes by speculating on how
      services may change in the future and emphasises the need for the UK to follow
      the United States in developing more professional approaches in this area and
      ensuring that rehabilitation staff receive proper training. 

PMID- 24441751
TI  - An attempt to work rehabilitation after long sick-leave.
AB  - Because of the increasing frequency of sick-leave in Sweden the General Health
      Insurance has directed funds for active rehabilitation by studying the
      possibilities for long-time sick-leave patients to go back to work. In the
      present study 38 subjects were randomized to an intervention group and a control
      group and followed for 3 years. In the intervention group, individual
      rehabilitation programs were provided and the patients were encouraged to
      actively deal with and improve their working situation. Also, they were
      influenced to accept activity and an active life style with a goal in life as an
      important and valuable concept. There was an obvious tendency of those in the
      intervention group to return to work more readily, however, the difference
      between the groups was not statistically significant. 

PMID- 24441752
TI  - WorkAbility Mark III: functional assessment of workplace capabilities.
AB  - Standardized measurement of workplace performance or the functional assessment of
      an individual's capabilities, especially by occupational therapists, is often
      critical before injured workers are returned to work, placed in new jobs, or
      evaluated for job incapacity. A direct link between a clinician's systematic
      findings and the detailed requirements of the workplace is desirable. There are a
      range of vocational evaluation systems available. This study examines how one of
      these systems, WorkAbility Mark III, incorporates a work measurement technique of
      industrial engineering into occupational therapy practice. The results of this
      study suggest that functional assessment with WorkAbility Mark III has benefits
      for the major stakeholders in occupational rehabilitation; that WorkAbility Mark
      III tests and uses six activity groups of workplace elements throughout the work
      assessment process; and that computer technology in this area of occupational
      rehabilitation can assist the clinician in his or her assessment, planning,
      intervention, and evaluation. 

PMID- 24441753
TI  - Interview skills training for people with psychiatric disabilities: a review of
      the literature.
AB  - Vocational rehabilitation or integration is a growing concern for people with
      psychiatric disabilities and mental health professionals. One of the key steps
      towards successful vocational outcome is to be competent in job interview skills,
      to form a favourable impression on job interviewers and to ultimately lead to a
      positive hiring decision. People with psychiatric disabilities have difficulties
      in managing job interviews effectively due to various reasons. This paper reviews
      seven studies on the effectiveness of job interview skills training for the
      sample of people with psychiatric disabilities. In view of some of the concerns
      identified in those previous studies, and in recent work rehabilitation
      literature, it is proposed that the job interview skills training should address
      the following issues: manifested adjustment, ability to communicate, concept of
      self-efficacy, skills generalisation, vocational rehabilitation versus
      integration and social validity of training materials. 

PMID- 24441754
TI  - Human rights and health: a workshop for health professionals.

PMID- 24441755
TI  - Perspectives from the field.

PMID- 24441758
TI  - Volume contentsVolume 7 (1996).

PMID- 24441759
TI  - Aesthetic and sensory reconstruction of finger pulp defects using free toe flaps.
AB  - BACKGROUND: This study illustrates aesthetic and sensory reconstruction of finger
      pulp defects with free toe flaps from the lateral aspect of the great toe or the
      medial aspect of the second toe. METHODS: Between August 2007 and July 2010, free
      toe flaps were harvested and used for 21 fingers of 21 patients. The average
      patient age was 34.5 years (range 19-62 years). The soft tissue defects were
      found in the thumb of 6 patients, the index finger of 7 patients, the middle
      finger of 5 patients, and the ring finger of 3 patients. The donor site was the
      great toe for 9 patients and the second toe for 12 patients. The average flap
      size was 2.8 * 2.0 cm (range 1.7 * 1.7 to 3.5 * 3.0 cm). Restoration of the
      sensitivity, aesthetic appearance, and mobility of the injured fingers compared
      with the opposite side was assessed using appropriate tools during the follow-up
      time. RESULTS: All the flaps in this series survived completely, with a high
      survival rate of 100 %. No urgent operative revision necessitated by
      postoperative thrombosis of the vessels was performed during the follow-up
      period. During a mean follow-up period of 18.4 months (range 12-24 months), the
      average static two-point discrimination score for the injured finger pulp was 4.8
      mm (range 3-7 mm), and the Michigan Hand Outcome Questionnaire score was 4.9 mm.
      The mean range of motion of the distal interphalangeal joint in the injured
      finger was 69.7 degrees . CONCLUSION: Transplantation of free microvascular flaps
      from the great toe or the second toe is a useful and reliable technique for
      finger pulp defect reconstruction. LEVEL OF EVIDENCE V: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 24441760
TI  - Commentary on Facial rejuvenation with fine barbed threads: the simple MIZ-lift.

PMID- 24441761
TI  - High-purity iron pyrite (FeS2) nanowires as high-capacity nanostructured cathodes
      for lithium-ion batteries.
AB  - Iron pyrite is an earth-abundant and inexpensive material that has long been
      interesting for electrochemical energy storage and solar energy conversion. A
      large-scale conversion synthesis of phase-pure pyrite nanowires has been
      developed for the first time. Nano-pyrite cathodes exhibited high Li-storage
      capacity and excellent capacity retention in Li/pyrite batteries using a liquid
      electrolyte, which retained a discharge capacity of 350 mAh g(-1) and a discharge
      energy density of 534 Wh kg(-1) after 50 cycles at 0.1 C rate. 

PMID- 24441763
TI  - Strain-assisted, low-temperature synthesis of high-performance thermoelectric
      materials.
AB  - Utilizing internal energy artificially implemented by cold-pressing in the
      specimens, we demonstrate a way to synthesize high-quality bulk thermoelectric
      materials at otherwise too low a temperature to approach to an equilibrium state.
      This low-temperature synthesis technique will provide a new opportunity to
      integrate high-performance thermoelectric materials into various electronic
      devices for a built-in energy source, as well as to develop low-cost fabrication
      methods. 

PMID- 24441762
TI  - Cell-cycle regulation in green algae dividing by multiple fission.
AB  - Green algae dividing by multiple fission comprise unrelated genera but are
      connected by one common feature: under optimal growth conditions, they can divide
      into more than two daughter cells. The number of daughter cells, also known as
      the division number, is relatively stable for most species and usually ranges
      from 4 to 16. The number of daughter cells is dictated by growth rate and is
      modulated by light and temperature. Green algae dividing by multiple fission can
      thus be used to study coordination of growth and progression of the cell cycle.
      Algal cultures can be synchronized naturally by alternating light/dark periods so
      that growth occurs in the light and DNA replication(s) and nuclear and cellular
      division(s) occur in the dark; synchrony in such cultures is almost 100% and can
      be maintained indefinitely. Moreover, the pattern of cell-cycle progression can
      be easily altered by differing growth conditions, allowing for detailed studies
      of coordination between individual cell-cycle events. Since the 1950s, green
      algae dividing by multiple fission have been studied as a unique model for cell
      cycle regulation. Future sequencing of algal genomes will provide additional,
      high precision tools for physiological, taxonomic, structural, and molecular
      studies in these organisms. 

PMID- 24441764
TI  - Radioactive substances legislative amendments in the UK: concepts employed in the
      development of the new exclusion and exemption regime.
AB  - A new radioactive substances regulatory regime came into effect across the UK on
      1 October 2011, accompanied by Government and regulator's guidance. The
      legislation sets new activity thresholds for what is within its scope and for
      what is exempt from the permitting requirements. These thresholds are, for the
      first time, clearly based on the levels in the Basic Safety Standards Directive;
      distinguish between NORM industrial activities and practices; and are derived
      from different dose constraints. There are new exemption provisions for NORM,
      aqueous liquids and gaseous wastes. 

PMID- 24441765
TI  - TR-DB: an open-access database of compounds affecting the ethylene-induced triple
      response in Arabidopsis.
AB  - Small molecules which act as hormone agonists or antagonists represent useful
      tools in fundamental research and are widely applied in agriculture to control
      hormone effects. High-throughput screening of large chemical compound libraries
      has yielded new findings in plant biology, with possible future applications in
      agriculture and horticulture. To further understand ethylene
      biosynthesis/signaling and its crosstalk with other hormones, we screened a
      12,000 compound chemical library based on an ethylene-related bioassay of dark
      grown Arabidopsis thaliana (L.) Heynh. seedlings. From the initial screening,
      1313 (~11%) biologically active small molecules altering the phenotype triggered
      by the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), were
      identified. Selection and sorting in classes were based on the angle of curvature
      of the apical hook, the length and width of the hypocotyl and the root. A MySQL
      database was constructed (https://chaos.ugent.be/WE15/) including basic chemical
      information on the compounds, images illustrating the phenotypes, phenotype
      descriptions and classification. The research perspectives for different classes
      of hit compounds will be evaluated, and some general screening tips for
      customized high-throughput screening and pitfalls will be discussed. 

PMID- 24441766
TI  - Effect of fosinopril on the transient outward potassium current of hypertrophied
      left ventricular myocardium in the spontaneously hypertensive rat.
AB  - To investigate fosinopril's effect on the transient outward potassium current
      (Ito) of differing degrees of hypertrophied myocytes in the spontaneously
      hypertensive rat (SHR). Ten- and 24-week-old SHRs were used as models for cardiac
      hypertrophy. Hypertrophied ventricular myocytes were exposed to 1, 10, and 100
      MUmol/L fosinopril; the whole-cell patch-clamp technique was used to study the
      effects on the transient outward potassium current. Ito current density was
      decreased in SHR myocytes relative to controls (14.17 +/- 0.31 and 11.62 +/- 0.08
      pA/pF in 10- and 24-week-old SHR versus 16.73 +/- 0.15 pA/pF, p < 0.01). Higher
      concentrations of fosinopril (10 and 100 MUmol/L) increased Ito peak current
      density in 10-week-old SHR myocytes compared with controls (14.92 +/- 0.14 and
      15.27 +/- 0.13 pA/pF versus 14.17 +/- 0.31 pA/pF, p < 0.01). Fosinopril increased
      Ito peak current density in 24-week-old SHR myocytes at all doses (12.70 +/-
      0.07, 13.74 +/- 0.10, and 14.53 +/- 0.13 versus 11.62 +/- 0.08 pA/pF for
      controls, p < 0.01). Fosinopril had a greater Ito elevation potential on
      hypertrophied myocytes in 24-week-old compared with 10-week-old SHR for each dose
      (1.08 +/- 0.09 versus 0.37 +/- 0.26 pA/pF, p < 0.01; 2.13 +/- 0.05 versus 0.75 +/
      0.35 pA/pF, p < 0.01; 2.92 +/- 0.07 versus 1.10 +/- 0.40 pA/pF, p < 0.01).
      Fosinopril increased Ito current density in hypertrophied myocytes. This effect
      was more pronounced in myocytes with a greater degree of hypertrophy.

PMID- 24441768
TI  - RTS noise and dark current white defects reduction using selective averaging
      based on a multi-aperture system.
AB  - In extremely low-light conditions, random telegraph signal (RTS) noise and dark
      current white defects become visible. In this paper, a multi-aperture imaging
      system and selective averaging method which removes the RTS noise and the dark
      current white defects by minimizing the synthetic sensor noise at every pixel is
      proposed. In the multi-aperture imaging system, a very small synthetic F-number
      which is much smaller than 1.0 is achieved by increasing optical gain with
      multiple lenses. It is verified by simulation that the effective noise normalized
      by optical gain in the peak of noise histogram is reduced from 1.38e- to 0.48 e-
      in a 3 * 3-aperture system using low-noise CMOS image sensors based on folding
      integration and cyclic column ADCs. In the experiment, a prototype 3 * 3-aperture
      camera, where each aperture has 200 * 200 pixels and an imaging lens with a focal
      length of 3.0 mm and F-number of 3.0, is developed. Under a low-light condition,
      in which the maximum average signal is 11e- per aperture, the RTS and dark
      current white defects are removed and the peak signal-to-noise ratio (PSNR) of
      the image is increased by 6.3 dB. 

PMID- 24441769
TI  - Enhancement of the excitation efficiency of the non-contact magnetostrictive
      sensor for pipe inspection by adjusting the alternating magnetic field axial
      length.
AB  - The non-contact magnetostrictive sensor (MsS) has been widely used in the guided
      wave testing of pipes, cables, and so on. However, it has a disadvantage of low
      excitation efficiency. A new method for enhancing the excitation efficiency of
      the non-contact MsS for pipe inspection using guided waves, by adjusting the
      axial length of the excitation magnetic field, is proposed. A special transmitter
      structure, in which two copper rings are added beside the transmitter coil, is
      used to adjust the axial length at the expense of weakening the excitation
      magnetic field. An equivalent vibration model is presented to analyze the
      influence of the axial length variation. The final result is investigated by
      experiments. Results show that the excitation efficiency of the non-contact MsS
      is enhanced in the whole inspection frequency range of the L(0,2) mode if the
      axial length is adjusted to a certain value. Moreover that certain axial length
      is the same for pipes of different sizes but made of the same material. 

PMID- 24441767
TI  - Domain-specific effects of prenatal exposure to PCBs, mercury, and lead on infant
      cognition: results from the Environmental Contaminants and Child Development
      Study in Nunavik.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs), methylmercury (MeHg), and lead (Pb)
      are environmental contaminants known for their adverse effects on cognitive
      development. OBJECTIVES: In this study we examined the effects of prenatal
      exposure to PCBs, MeHg, and Pb on cognitive development in a sample of Inuit
      infants from Arctic Quebec. METHODS: Mothers were recruited at local prenatal
      clinics. PCBs, mercury (Hg), Pb, and two seafood nutrients-docosahexaenoic acid
      (DHA) and selenium (Se)-were measured in umbilical cord blood. Infants (n = 94)
      were assessed at 6.5 and 11 months of age on the Fagan Test of Infant
      Intelligence (FTII), A-not-B test, and Bayley Scales of Infant Development-2nd
      Edition (BSID-II). RESULTS: Multiple regression analyses revealed that higher
      prenatal PCB exposure was associated with decreased FTII novelty preference,
      indicating impaired visual recognition memory. Prenatal Hg was associated with
      poorer performance on A-not-B, which depends on working memory and is believed to
      be a precursor of executive function. Prenatal Pb was related to longer FTII
      fixation durations, indicating slower speed of information processing.
      CONCLUSIONS: PCBs, MeHg, and Pb each showed specific and distinct patterns of
      adverse associations with the outcomes measured during infancy. By contrast, none
      of these exposures was associated with performance on the BSID-II, a global
      developmental measure. The more focused, narrow band measures of cognitive
      function that appeared to be sensitive to these exposures also provide early
      indications of long-term impairment in specific domains that would otherwise not
      likely be evident until school age. CITATION: Boucher O, Muckle G, Jacobson JL,
      Carter RC, Kaplan-Estrin M, Ayotte P, Dewailly E, Jacobson SW. 2014. Domain
      specific effects of prenatal exposure to PCBs, mercury, and lead on infant
      cognition: results from the Environmental Contaminants and Child Development
      Study in Nunavik. Environ Health Perspect 122:310-316;
      http://dx.doi.org/10.1289/ehp.1206323.

PMID- 24441770
TI  - In-line measurement of water content in ethanol using a PVA-coated quartz crystal
      microbalance.
AB  - An in-line device for measuring the water content in ethanol was developed using
      a polyvinyl alcohol (PVA)-coated quartz crystal microbalance. Bio-ethanol is
      widely used as the replacement of gasoline, and its water content is a key
      component of its specifications. When the PVA-coated quartz crystal microbalance
      is contacted with ethanol containing a small amount of water, the water is
      absorbed into the PVA increasing the load on the microbalance surface to cause a
      frequency drop. The determination performance of the PVA-coated microbalance is
      examined by measuring the frequency decreases in ethanol containing 2% to 10%
      water while the ethanol flows through the measurement device. The measurements
      indicates that the higher water content is the more the frequency reduction is,
      though some deviation in the measurements is observed. This indicates that the
      frequency measurement of an unknown concentration of water in ethanol can be used
      to determine the water content in ethanol. The PVA coating is examined by
      microscopy and FTIR (Fourier transform infrared) spectroscopy. 

PMID- 24441772
TI  - NSC746364, a G-quadruplex-stabilizing agent, suppresses cell growth of A549 human
      lung cancer cells through activation of the ATR/Chk1-dependent pathway.
AB  - The telomere is considered to be a potential target for cancer therapy.
      NSC746364, a novel G-quadruplex-stabilizing agent, has been found to have
      cytotoxic effects on various cancer cells. To date, its pharmacological
      mechanisms are still unknown. The goal of this study was to investigate the
      molecular mechanisms of NSC746364 on the A549 human lung adenocarcinoma cell
      line. For this, we used a wide variety of in vitro assays. The intracellular
      signaling pathways including DNA damage sensing and response proteins, cell cycle
      regulatory proteins, and some key executors involved in apoptosis were evaluated
      in this study. Our study suggested that NSC746364 induced cell cycle arrest at
      the G2/M phase and triggers programming cell death on A549 human lung cancer
      cells, whose effects are modulated through the activation of the ATR/Chk1
      pathway, the downregulation of cyclin B1 expression, and the activation of
      caspase-3. Consequently, our results indicated that NSC746364 may have
      therapeutic potential as a chemotherapy for non-small-cell lung cancers.

PMID- 24441773
TI  - Osthole augments therapeutic efficiency of neural stem cells-based therapy in
      experimental autoimmune encephalomyelitis.
AB  - The therapeutic potential of adult neural stem cells (NSCs)-derived from bone
      marrow (BM) has been recently described in experimental autoimmune
      encephalomyelitis (EAE), an animal model of multiple sclerosis; however, the
      beneficial effects are modest due to their marginal anti-inflammatory capacity.
      To overcome this weakness and endow BM-NSC therapy with profound anti
      inflammatory capacity, in this study we pretreated EAE mice with osthole, a
      natural coumarin with a broad spectrum of pharmacological activities, including
      anti-inflammation, immunomodulation, and neuroprotection, before NSC-application
      and continued throughout the study. We found that osthole conferred a potent anti
      inflammatory capacity to this BM-NSC therapy, thus more profoundly suppressing
      ongoing EA and exhibiting significant advantages over conventional NSC-therapy as
      follows: 1) Enhanced anti-inflammatory effect, thus improving survival
      environment for engrafted BM-NSCs and protecting myelin sheaths from further
      demyelination; 2)Drove transplanted (exogenous) BM-NSCs to differentiate into
      more oligodendrocytes and neurons but inhibited differentiation into astrocytes,
      thus promoting remyelination and axonal growth, and reducing astrogliosis; and 3)
      augmented CNS neurotrophic support thus promoted resident (endogenous) repair of
      myelin/axonal damage. These effects make the BM-NSCs-based therapy a more
      promising approach to enhance remyelination and neuronal repopulation, thus more
      effectively promoting anatomic and functional recovery from neurological
      deficits. 

PMID- 24441771
TI  - Hyperpolarized NMR probes for biological assays.
AB  - During the last decade, the development of nuclear spin polarization enhanced
      (hyperpolarized) molecular probes has opened up new opportunities for studying
      the inner workings of living cells in real time. The hyperpolarized probes are
      produced ex situ, introduced into biological systems and detected with high
      sensitivity and contrast against background signals using high resolution NMR
      spectroscopy. A variety of natural, derivatized and designed hyperpolarized
      probes has emerged for diverse biological studies including assays of
      intracellular reaction progression, pathway kinetics, probe uptake and export,
      pH, redox state, reactive oxygen species, ion concentrations, drug efficacy or
      oncogenic signaling. These probes are readily used directly under natural
      conditions in biofluids and are often directly developed and optimized for
      cellular assays, thus leaving little doubt about their specificity and utility
      under biologically relevant conditions. Hyperpolarized molecular probes for
      biological NMR spectroscopy enable the unbiased detection of complex processes by
      virtue of the high spectral resolution, structural specificity and
      quantifiability of NMR signals. Here, we provide a survey of strategies used for
      the selection, design and use of hyperpolarized NMR probes in biological assays,
      and describe current limitations and developments. 

PMID- 24441775
TI  - From the editor.

PMID- 24441776
TI  - Upper extremity cumulative trauma disorder and return to work assessment.
AB  - Evaluation of the patient with upper limb cumulative trauma disorder (CTD)
      requires use of both qualitative and quantitative measures. The clinical
      evaluations are reviewed, which include tests for range of motion, strength, limb
      size, sensation, and dexterity. Essential observations for identifying and
      describing the presentation of posture, symptoms, and painful events are
      illustrated for qualitative descriptions related to work activities and
      activities of daily living (ADL). Therapeutic intervention is described in two
      sequential stages: calming of symptoms and then control of symptoms. 

PMID- 24441774
TI  - Space charge neutralization by electron-transparent suspended graphene.
AB  - Graphene possesses many fascinating properties originating from the manifold
      potential for interactions at electronic, atomic, or molecular levels. Here we
      report measurement of electron transparency and hole charge induction response of
      a suspended graphene anode on top of a void channel formed in a SiO2/Si
      substrate. A two-dimensional (2D) electron gas induced at the oxide interface
      emits into air and makes a ballistic transport toward the suspended graphene. A
      small fraction (>~0.1%) of impinging electrons are captured at the edge of 2D
      hole system in graphene, demonstrating good transparency to very low energy (<3
      eV) electrons. The hole charges induced in the suspended graphene anode have the
      effect of neutralizing the electron space charge in the void channel. This charge
      compensation dramatically enhances 2D electron gas emission at cathode to the
      level far surpassing the Child-Langmuir's space-charge-limited emission. 

PMID- 24441777
TI  - VDT ergonomics: upper extremity assessment requires a holistic approach.
AB  - Repetitive strain injuries (RSI) of the hand and upper extremity have been linked
      to video display terminals (VDT). The incidence of RSI has increased with the
      proliferation of computer use in the workplace and at home. A holistic approach
      to dealing with upper extremity RSI begins with the seated position. Simple
      adjustments made here can correct much of the poor positioning of the shoulders,
      arms, and hands. The rest of the workstation can then be designed around the
      correctly seated VDT user. In addition to being instructed in appropriate seating
      and posture, the VDT user must also learn proper keyboard technique, work pacing
      and rotation, and exercises to stretch shortened muscles and strengthen
      overstretched muscles. A checklist to review the basic components of a VDT
      ergonomic analysis has been developed. 

PMID- 24441778
TI  - Preliminary outcome evaluation efforts: utilization review and patient health
      survey results.
AB  - Preliminary efforts to perform outcome evaluation at 20 outpatient rehabilitation
      facilities are presented, including utilization review and a patient satisfaction
      survey. Therapy services assessed in this initial phase ranged from acute care to
      work hardening and included patients with a wide variety of upper extremity
      diagnoses. Patients' perception of their general health status was assessed using
      the Short Form General Health Survey following discharge from therapy. Plans for
      improved outcome evaluation and development of critical pathways are included. 

PMID- 24441779
TI  - Inter-rater agreement and accuracy of clinical tests used in diagnosis of Carpal
      Tunnel Syndrome.
AB  - A sample of 42 subjects (84 hands) with complaints of pain, numbness and/or
      tingling were used to study the inter-rater agreement and accuracy of seven
      clinical tests which can be used to assist in the diagnosis of carpal tunnel
      syndrome (CTS). A 'gold standard diagnosis', defined as a clinical diagnosis of
      CTS rendered by one of two hand surgeons and supported by electrodiagnostic
      evidence of CTS, was used to classify the 84 hands as to the presence of CTS. Two
      therapists were blinded to patient history, electrophysiology, diagnosis and all
      evaluations performed by the other therapist, until clinical testing was
      completed. Tests performed included: wrist flexion, wrist extension, Tinel's,
      tethered median nerve (TMN), pinch, vibration and Semmes-Weinstein monofilament
      (SWMF) tests. Substantial inter-rater agreement was observed between the two
      therapists for five of the clinical tests (k > 0.71) with SWMF and TMN having
      lower agreement. The most accurate test was Phalen's wrist flexion test. Good
      accuracy was demonstrated by pinch and vibration tests. Tinel's test was
      characterized by lower sensitivity, but false positives were rare. Wrist
      extension and TMN tests had poor sensitivity. SWMF testing was very sensitive,
      but a high number of false positives occurred when 'normal' was classified as
      2.83. Reliability and accuracy of these tests supports their use as components of
      a clinical diagnosis of CTS. 

PMID- 24441780
TI  - Repetitive strain injury: A new definition and treatment strategy based on the
      client-centered practice.
AB  - RSI is defined by the authors as a biopsychosocial disorder, under the umbrella
      of cumulative trauma disorder, involving a non-specific, potentially chronic pain
      syndrome of the upper extremity. Evaluation and treatment will focus on the
      client-centered practice. Patients are enrolled in an 8-week course of treatment,
      which focuses on patient involvement, education, relaxation, diaphragmatic
      breathing, exercise, postural modification, as well as assessing vocational and
      psychosocial issues. 

PMID- 24441781
TI  - Ergonomic strategies for dental professionals.
AB  - This study examined the extent to which dental professionals have made changes
      within their practice environments to decrease the potential for developing a
      cumulative trauma disorder. A survey was disseminated to a sample of 95 dental
      professionals. The survey addressed the presence and location of pain, changes
      professionals made within their workplaces, and whether or not these changes were
      perceived as effective. Fifty two surveys were returned for a response rate of
      55%. Results indicated that 96% noted pain during or after work; 88% had made
      changes in their work practices. Common strategies used to promote health were
      stretching, good posture, personal relaxation, and instrument maintenance. Use of
      ergonomic instruments, workstations, and new instrumentation strategies were seen
      as effective, but rated slightly lower than other categories. 

PMID- 24441782
TI  - Non-work issues that affect successful return to work for upper extremity injured
      employees.
AB  - This case report demonstrates the difficulty in treating women who are being
      abused within their environments. A frequent site of injury is the upper
      extremity. This issue may have significant effects on desired outcomes and should
      be properly assessed to improve intervention, return to work, and programs
      following discharge. 

PMID- 24441783
TI  - Management of a patient with a ring avulsion injury.
AB  - The purpose of this report is to describe the management of a patient with a
      Class I ring avulsion injury. There were no bony or skeletal injuries and both
      neurovascular bundles were intact, but soft tissue swelling and decreased range
      of motion contributed to complex management problems. Predictable patterns of
      range of motion limitations, secondary to adhesion formation, were addressed
      early in the rehabilitation program with tendon gliding exercises. Proximal
      interphalangeal extension splinting was initiated to combat a flexion contracture
      which is common when digital edema is present. Edema control techniques and scar
      management were also part of the hand therapy regimen. Careful assessment at each
      session and tissue response to exercise dictated changes in the hand therapy
      program. Emphasis on patient education and a comprehensive home program
      facilitated an early return to work. 

PMID- 24441784
TI  - The 10% rule: grip strength and hand dominance in a factory population.
AB  - This study examined the applicability of the 10% rule and the possible effect of
      years of work experience on the percent difference in grip strength for a sample
      of 124 factory workers in Indiana. The overall mean percent difference in grip
      strength, measured by the Jamar dynamometer, for both right- and left-handed
      participants was 6.3079%. A statistical difference was found (P = 0.029) in
      percent difference in grip strength among subjects with varying years of work
      experience. A significant difference (P = 0.007) also existed when comparing the
      right-handed scores to the left-handed scores of the Edinburgh Inventory. Results
      suggest that establishing grip strength norms for factory workers should not be
      determined by a percent difference rule, and the years of work experience need to
      be taken into consideration. 

PMID- 24441785
TI  - Tuberculosis: a global emergency.
AB  - This paper presents an analysis of Tuberculosis (TB). Specifically addressed are
      the history of its development and treatment; its current resurgence; the global
      impact of this resurgence; the social issues responsible for the resurgence
      including poverty, homelessness, substance abuse, the HIV/AIDS epidemic, and
      increased immigration from TB endemic areas of the world; and the political,
      economic and ethical issues affecting its incidence today including inadequate
      funding, California's Proposition 187, pharmaceutical corporation profit motives,
      directly observed therapy and forced confinement of non-compliant patients. 

PMID- 24441787
TI  - The disillusioned employer and ergonomics: suggestions for improvement.

PMID- 24441786
TI  - Cumulative trauma disorders - What does 'light duty' mean?

PMID- 24441791
TI  - An exquisitely preserved troodontid theropod with new information on the palatal
      structure from the Upper Cretaceous of Mongolia.
AB  - Troodontidae is a clade of small-bodied theropod dinosaurs. A new troodontid,
      Gobivenator mongoliensis gen. et sp. nov., is described based on the most
      complete skeleton of a Late Cretaceous member of this clade presently known, from
      the Campanian Djadokhta Formation in the central Gobi Desert. G. mongoliensis is
      different from other troodontids in possessing a pointed anterior end of the
      fused parietal and a fossa on the surangular in front of the posterior surangular
      foramen. The skull was superbly preserved in the specimen and provides detailed
      information of the entire configuration of the palate in Troodontidae. Overall
      morphology of the palate in Gobivenator resembles those of dromaeosaurids and
      Archaeopteryx, showing an apparent trend of elongation of the pterygoid process
      of the palatine and reduction of the pterygopalatine suture toward the basal
      Avialae. The palatal configuration suggests that the skull of Gobivenator would
      have been akinetic but had already acquired prerequisites for later evolution of
      cranial kinesis in birds, such as the loss of the epipterygoid and reduction in
      contact areas among bones.

PMID- 24441790
TI  - Inducible nitric oxide synthase is a major intermediate in signaling pathways for
      the survival of plasma cells.
AB  - While a number of extrinsic factors are known to promote the survival of plasma
      cells (PCs), the signaling intermediates involved remain poorly characterized.
      Here we identified inducible nitric oxide synthase (iNOS) as an intermediate that
      supported the survival of PCs. PCs deficient in iNOS (Nos2(-/-) PCs) showed
      enhanced death in vitro, after transfer into congenic adoptive hosts, and in
      chimeras made with wild-type and Nos2(-/-) bone marrow. The iNOS-mediated
      protection involved activation of protein kinase G and modulation of endoplasmic
      reticulum stress components. Activation of caspases was also diminished. We found
      that iNOS was required for PCs to respond to some prosurvival mediators
      associated with bone marrow stromal cells and that at least one mediator,
      interleukin 6, fed directly into this pathway by inducing iNOS. 

PMID- 24441789
TI  - The unfolded-protein-response sensor IRE-1alpha regulates the function of
      CD8alpha+ dendritic cells.
AB  - The role of the unfolded protein response (UPR) and endoplasmic reticulum (ER)
      stress in homeostasis of the immune system is incompletely understood. Here we
      found that dendritic cells (DCs) constitutively activated the UPR sensor IRE
      1alpha and its target, the transcription factor XBP-1, in the absence of ER
      stress. Loss of XBP-1 in CD11c+ cells led to defects in phenotype, ER homeostasis
      and antigen presentation by CD8alpha+ conventional DCs, yet the closely related
      CD11b+ DCs were unaffected. Whereas the dysregulated ER in XBP-1-deficient DCs
      resulted from loss of XBP-1 transcriptional activity, the phenotypic and
      functional defects resulted from regulated IRE-1alpha-dependent degradation
      (RIDD) of mRNAs, including those encoding CD18 integrins and components of the
      major histocompatibility complex (MHC) class I machinery. Thus, a precisely
      regulated feedback circuit involving IRE-1alpha and XBP-1 controls the
      homeostasis of CD8alpha+ conventional DCs.

PMID- 24441792
TI  - Latex micro-balloon pumping in centrifugal microfluidic platforms.
AB  - Centrifugal microfluidic platforms have emerged as point-of-care diagnostic
      tools. However, the unidirectional nature of the centrifugal force limits the
      available space for multi-step processes on a single microfluidic disc. To
      overcome this limitation, a passive pneumatic pumping method actuated at high
      rotational speeds has been previously proposed to pump liquid against the
      centrifugal force. In this paper, a novel micro-balloon pumping method that
      relies on elastic energy stored in a latex membrane is introduced. It operates at
      low rotational speeds and pumps a larger volume of liquid towards the centre of
      the disc. Two different micro-balloon pumping mechanisms have been designed to
      study the pump performance at a range of rotational frequencies from 0 to 1500
      rpm. The behaviour of the micro-balloon pump on the centrifugal microfluidic
      platforms has been theoretically analysed and compared with the experimental
      data. The experimental data show that the developed pumping method dramatically
      decreases the required rotational speed to pump liquid compared to the previously
      developed pneumatic pumping methods. It also shows that within a range of
      rotational speed, a desirable volume of liquid can be stored and pumped by
      adjusting the size of the micro-balloon. 

PMID- 24441793
TI  - Laparoscopic approach for inflammatory bowel disease is a real alternative to
      open surgery: an experience with 574 consecutive patients.
AB  - OBJECTIVE: This study aimed to report a 14-year experience of laparoscopic
      approach for inflammatory bowel disease (IBD), including complicated and
      recurrent cases. BACKGROUND: Feasibility of laparoscopic approach for IBD
      surgical management has been questioned. METHODS: From 1998 to 2012, all patients
      undergoing colorectal resection for IBD were prospectively enrolled. Adjusted
      risks of conversion and severe postoperative morbidity after laparoscopic
      resection were computed, according to a multivariate regression logistic model.
      RESULTS: A total of 790 consecutive resections for IBD were performed on 633
      patients. Laparoscopic approach was performed in 574 (73%) procedures, including
      286 ileocecal resections (48%), 118 subtotal colectomies (19%), 134 ileal pouch
      anal anastomoses (21%), 23 segmental colectomies (8%), and 18 abdominoperineal
      resections (4%). A total of 145 (25%) complex laparoscopic procedures were
      performed, considered as such because of iterative surgery for IBD recurrence (n
      = 66, 12%) or because of intra-abdominal-abscess or fistula (n = 93, 16%).
      Conversion to laparotomy occurred in 67 procedures (12%). Postoperative death
      occurred in 1 patient (0.2%). Severe postoperative morbidity occurred in 66
      laparoscopic procedures (13%). Splitting the study in 5 time periods, the rate of
      laparoscopic procedures significantly increased from 42% in period 1 to 80% in
      period 5 (P < 0.001). With time, the rate of complex procedures performed
      laparoscopically significantly increased (P = 0.023), whereas both mean adjusted
      risks of conversion and severe postoperative morbidity significantly decreased (P
      < 0.001). CONCLUSIONS: Laparoscopic approach is a safe and effective alternative
      to open surgery for IBD management. With growing experience, the rate of
      laparoscopic complex procedures increased, whereas adjusted risks of conversion
      and severe postoperative morbidity significantly decreased.

PMID- 24441794
TI  - Early severe acute pancreatitis: a subgroup of critical acute pancreatitis.

PMID- 24441795
TI  - Concerns About Acute Cholecystitis: Early Versus Delayed Cholecystectomy--A
      Multicenter Randomized Trial.

PMID- 24441796
TI  - Durability of Roux-en-Y gastric bypass surgery: a meta-regression study.

PMID- 24441797
TI  - Reply to Letter: "ATLS Protocols of Initial Intravenous Fluid Administration for
      Trauma Patients; Needing a Revision?".

PMID- 24441798
TI  - Reply to Letter: "Defining 'The Elderly' Undergoing Major Gastrointestinal
      Resections: Receiver Operating Characteristic Analysis of a Large ACS-NSQIP
      Cohort".

PMID- 24441799
TI  - Defining "The Elderly" Undergoing Major Gastrointestinal Resections: Receiver
      Operating Characteristic Analysis of a Large ACS-NSQIP Cohort.

PMID- 24441800
TI  - Optimization of staging of the neck with prophylactic central and lateral neck
      dissection for papillary thyroid carcinoma.

PMID- 24441801
TI  - The timing of antibiotic therapy must be controlled for when assessing
      appendectomy outcomes.

PMID- 24441802
TI  - Determinant-based classification of severity of acute pancreatitis: have we
      really reached consensus?

PMID- 24441803
TI  - Increasing the Quality of Surgery for Deep Endometriosis Should Be Based on
      Homogenous Clinical Patient Phenotype, Surgical Experience, and Standardized
      Outcome Reporting in Multicenter Multisurgeon Prospective Trials.

PMID- 24441804
TI  - Re: Fibrin sealant for prevention of resection surface-related complications
      after liver resection: a randomized controlled trial.

PMID- 24441805
TI  - Reply to letter: "Progress in the diagnosis of appendicitis".

PMID- 24441806
TI  - Predictive factors for postoperative pancreatic fistula.

PMID- 24441807
TI  - Failure to rescue in trauma patients: operative interventions must be considered.

PMID- 24441808
TI  - The mesocolon: a histological and electron microscopic characterization of the
      mesenteric attachment of the colon prior to and after surgical mobilization.
AB  - BACKGROUND: Colonic mobilization requires separation of mesocolon from underlying
      fascia. Despite the surgical importance of planes formed by these structures, no
      study has formally characterized their microscopic features. The aim of this
      study was to determine the histological and electron microscopic appearance of
      mesocolon, fascia, and retroperitoneum, prior to and after colonic mobilization.
      METHODS: In 24 cadavers, samples were taken from right, transverse, descending,
      and sigmoid mesocolon. In 12 cadavers, specimens were stained with hematoxylin
      and eosin (3 sections) or Masson trichrome (3 sections). In the second 12
      cadavers, lymphatic channels were identified by staining immunohistochemically
      for podoplanin. The ascending mesocolon was assessed with scanning electron
      microscopy. The above process was first conducted with the mesocolon in situ. The
      mesocolon was then surgically mobilized, and the process was repeated on
      remaining structures. RESULTS: The microscopic structure of mesocolon and
      associated fascia was consistent from ileocecal to mesorectal level. A surface
      mesothelium and underlying connective tissue were evident throughout. Fibrous
      septae separated adipocyte lobules. Where apposed to retroperitoneum, 2
      mesothelial layers separated mesocolon and underlying retroperitoneum. A
      connective tissue layer occurred between these (ie, Toldt's fascia). Lymphatic
      channels were evident both in mesocolic connective tissue and Toldt's fascia.
      After surgical separation of mesocolon and fascia both remained contiguous, the
      fascia remained in situ and the retroperitoneum undisturbed. CONCLUSIONS: The
      findings demonstrate that the contiguous mesocolon and retroperitoneum are
      separated by mesothelial and connective tissue layers. These properties generate
      the surgical planes (ie, meso- and retrofascial planes) exploited in colonic and
      mesocolic mobilization.

PMID- 24441809
TI  - Should adenocarcinoma of the esophagogastric junction be classified as gastric or
      esophageal cancer, or else as a distinct clinical entity?

PMID- 24441811
TI  - Is postoperative length of hospital stay a true surrogate marker of postoperative
      morbidity?

PMID- 24441810
TI  - Disparities in surgical 30-day readmission rates for Medicare beneficiaries by
      race and site of care.
AB  - OBJECTIVE: To determine whether black patients have higher odds of readmission
      than white patients after major surgery, and to ascertain whether these
      disparities are related to where black patients receive care. BACKGROUND: Racial
      disparities are known to exist for many aspects of surgical care. However, it is
      unknown if disparities exist in readmissions after a surgical procedure, an area
      which is becoming a prime focus for clinical leaders and policymakers. METHODS:
      Using national Medicare data from 2007 to 2010, we examined 30-day readmissions
      for patients undergoing coronary artery bypass grafting, pulmonary lobectomy,
      endovascular abdominal aortic aneurysm repair, open abdominal aortic aneurysm
      repair, colectomy, and hip replacement. The main outcome measure was risk
      adjusted odds of all-cause 30-day readmission. We used multivariate logistic
      regression to determine if black patients had higher readmission rates than white
      patients, and if so, whether this effect was mediated by the hospitals at which
      patients received care, or by poverty. RESULTS: Black patients had higher
      readmission rates than white patients (14.8% vs 12.8%, odds ratio [OR] 1.19; 95%
      confidence interval [CI], 1.16-1.22; P < 0.001). Patients undergoing major
      surgery at minority-serving hospitals also had higher readmission rates (14.3% vs
      12.8%, OR 1.14, 95% CI 1.09-1.19; P < 0.001). In multivariate analyses, black
      patients at minority-serving hospitals had the highest overall odds of
      readmissions (OR 1.34). White patients at minority-serving hospitals (OR 1.15)
      and black patients at non-minority-serving hospitals (OR 1.20) also had higher
      odds of readmission than the reference group of white patients at non-minority
      serving hospitals. Racial disparities were mediated in part by poverty.
      CONCLUSIONS: Among Medicare beneficiaries, black patients were more likely to be
      readmitted after hospitalization for surgical procedures. Since racial
      disparities in readmission rates are mediated both by patients' race and the
      hospital at which care is delivered, efforts at reducing disparities should focus
      not only on race-based measures but also on improving outcomes of care at
      minority-serving hospitals.

PMID- 24441812
TI  - Reply to letter: "Optimization of staging of the neck with prophylactic central
      and lateral neck dissection for papillary thyroid carcinoma".

PMID- 24441813
TI  - Reply to letter: "Regarding the impact of surgical delay in outcomes of patients
      undergoing appendectomy".

PMID- 24441814
TI  - The LAFA study.

PMID- 24441815
TI  - Primary anastomosis versus Hartmann's procedure for perforated diverticulitis
      with peritonitis: an impracticable trial.

PMID- 24441816
TI  - Nerve management and chronic pain after open inguinal hernia repair.

PMID- 24441818
TI  - Reply to letter: "Nerve management and chronic pain after open inguinal hernia
      repair".

PMID- 24441817
TI  - Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in
      patients undergoing liver transplantation: a Spanish matched cohort multicenter
      study.
AB  - OBJECTIVE: To evaluate the outcome of patients with hepatocellular
      cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on
      pathological examination after liver transplantation for HCC. BACKGROUND:
      Information on the outcome of cirrhotic patients undergoing a transplant for HCC
      and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS:
      Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients
      undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by
      pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC
      subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients
      compared with 30 controls. Patients were also divided according to the
      preoperative tumor size and number: uninodular tumors 2 cm or smaller and
      multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3
      142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed
      between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%,
      respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial
      survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs
      100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC
      CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9).
      Patients with uninodular tumors 2 cm or smaller in the study and control groups
      had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P
      = 0.4). In contrast, patients in the study group with multinodular or uninodular
      tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their
      controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS:
      Patients with HCC-CC have similar survival to patients undergoing a transplant
      for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of
      these patients from transplant option.

PMID- 24441819
TI  - Reply to letter: "the Surgical Mortality Probability Model (S-MPM): derivation
      and validation of a simple risk prediction rule for noncardiac surgery".

PMID- 24441820
TI  - Issues with "issues in general surgery residency training-2012".

PMID- 24441821
TI  - Reply to letter: "Analyzing the influence of blood loss on outcomes of cancer
      surgery".

PMID- 24441822
TI  - Retrograde aortic dissection after thoracic endovascular aortic repair.
AB  - OBJECTIVE: To provide data regarding the etiology and timing of retrograde type A
      aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR).
      METHODS: Details of patients who had RTAD after TEVAR were obtained from the
      MOTHER Registry supplemented by data from a systematic review of the literature.
      Univariate analysis and binary logistic regression analysis of patient or
      technical factors was performed. RESULTS: In MOTHER, RTAD developed in 16 of the
      1010 patients (1.6%). Binary logistic regression demonstrated that an indication
      of TEVAR for aortic dissection (acute P = 0.000212; chronic P = 0.006) and device
      oversizing (OR 1.14 per 1% increase in oversizing above 9%, P < 0.0001) were
      significantly more frequent in patients with RTAD. Data from the systematic
      review was pooled with MOTHER data and demonstrated that RTAD occurred in 1.7%
      (168/9894). Most of RTAD occurred in the immediate postoperative (58%) period and
      was associated with a high mortality rate (33.6%). The odds ratio of RTAD for an
      acute aortic dissection was 10.0 (CI: 4.7-21.9) and 3.4 (CI: 1.3-8.8) for chronic
      aortic dissection. The incidence of RTAD was not significantly different for
      endografts with proximal bare stent (2.8%) or nonbare stent (1.9%) (P = 0.1298).
      CONCLUSIONS: Although RTAD after TEVAR is an uncommon complication, it has a high
      mortality rate. RTAD is significantly more frequent in patients treated for acute
      and chronic type B dissection, and when the endograft is significantly oversized.
      The proximal endograft configuration was not associated with any difference in
      the incidence of RTAD.

PMID- 24441823
TI  - Sustained weight loss after gastric banding revision for pouch-related problems.
AB  - OBJECTIVE: To assess the impact of revisional surgery after laparoscopic
      adjustable gastric banding (LAGB) on weight loss at 12 and 24 months. BACKGROUND:
      There is no uniform consensus as to the optimal procedure for patients requiring
      revision after LAGB. Few studies address the issue of weight loss after band
      salvage procedures, despite this being a critical factor in deciding which
      reoperative procedure to choose. METHODS: A retrospective analysis was conducted
      of adult patients who underwent LAGB from January 1, 2001 to June 30, 2009 at a
      single institution. Patients who required revision for pouch-related problems
      including band slippage, pouch dilation, and hiatal hernia were studied.
      Demographic data, body mass index (BMI), percentage excess weight loss (% EWL),
      and operative details were recorded. Weights were recorded at 12 and 24 months
      after revision. These were compared with initial weight, weight before revision,
      and weight in patients who did not have a reoperation. RESULTS: Of 3876 patients,
      390 patients were included in analysis of weight outcomes after revision. The
      procedure-related mortality was 0%. Early (30-day) complications occurred in
      0.5%, late complications (erosion) in 0.5%, and 29 patients (7.4%) required a
      second revision. For patients undergoing revision, the initial weight was 124.06
      +/- 21.28 kg and BMI was 44.80 +/- 6.12 kg/m. At reoperation, weight was 89.18 +/
      20.51 kg, BMI was 32.25 +/- 6.50 kg/m and, %EWL was 54.13 +/- 21.80%. Twelve
      months postrevision, weight was 92.24 +/- 20.22 kg, BMI was 33.32 +/- 6.41 kg/m,
      and %EWL was 48.81 +/- 22.71%. Weight was 92.42 +/- 19.91 kg, BMI was 33.53 +/-
      6.25 kg/m, and %EWL was 47.50 +/- 22.91% twenty-four months postrevision.
      CONCLUSIONS: Reoperation for pouch-related problems after LAGB is safe and
      effective. Weight loss is maintained after reoperation.

PMID- 24441824
TI  - Reply to letter: "Open versus laparoscopic resection of primary tumor for
      incurable stage IV colorectal cancer: a large multicenter consecutive patients
      cohort study".

PMID- 24441825
TI  - Sendai Consensus Guidelines for Branch-duct IPMN: Guidelines Are Just Guidelines.

PMID- 24441826
TI  - Economic value of instream flow for non-commercial whitewater boating using
      recreation demand and contingent valuation methods.
AB  - Whitewater river kayaking and river rafting require adequate instream flows that
      are often adversely affected by upstream water diversions. However, there are
      very few studies in the USA of the economic value of instream flow to inform
      environmental managers. This study estimates the economic value of instream flow
      to non-commercial kayakers derived using a Travel Cost Method recreation demand
      model and Contingent Valuation Method (CVM), a type of Contingent Behavior Method
      (CBM). Data were obtained from a visitor survey administered along the Poudre
      River in Colorado. In the dichotomous choice CVM willingness to pay (WTP)
      question, visitors were asked if they would still visit the river if the cost of
      their trip was $Y higher, and the level of $Y was varied across the sample. The
      CVM yielded an estimate of WTP that was sensitive to flows ranging from $55 per
      person per day at 300 Cubic Feet per Second (CFS) to a maximum $97 per person per
      day at flows of 1900 CFS. The recreation demand model estimated a boater's number
      of trips per season. We found the number of trips taken was also sensitive to
      flow, ranging from as little as 1.63 trips at 300 CFS to a maximum number of 14
      trips over the season at 1900 CFS. Thus, there is consistency between peak
      benefits per trip and number of trips, respectively. With an average of about 100
      non-commercial boaters per day, the maximum marginal values per acre foot
      averages about $220. This value exceeds irrigation water values in this area of
      Colorado. 

PMID- 24441827
TI  - RIPK3 as a potential therapeutic target for Gaucher's disease.
AB  - Gaucher's disease (GD), an inherited metabolic disorder caused by mutations in
      the glucocerebrosidase gene (GBA), is the most common lysosomal storage disease.
      Heterozygous mutations in GBA are a major risk factor for Parkinson's disease. GD
      is divided into three clinical subtypes based on the absence (type 1) or presence
      (types 2 and 3) of neurological signs. Type 1 GD was the first lysosomal storage
      disease (LSD) for which enzyme therapy became available, and although infusions
      of recombinant glucocerebrosidase (GCase) ameliorate the systemic effects of GD,
      the lack of efficacy for the neurological manifestations, along with the
      considerable expense and inconvenience of enzyme therapy for patients, renders
      the search for alternative or complementary therapies paramount. Glucosylceramide
      and glucosylsphingosine accumulation in the brain leads to massive neuronal loss
      in patients with neuronopathic GD (nGD) and in nGD mouse models. However, the
      mode of neuronal death is not known. Here, we show that modulating the receptor
      interacting protein kinase-3 (Ripk3) pathway markedly improves neurological and
      systemic disease in a mouse model of GD. Notably, Ripk3 deficiency substantially
      improved the clinical course of GD mice, with increased survival and motor
      coordination and salutary effects on cerebral as well as hepatic injury. 

PMID- 24441830
TI  - Origin of the improved mobility and photo-bias stability in a double-channel
      metal oxide transistor.
AB  - This study examined the performance and photo-bias stability of double-channel
      ZnSnO/InZnO (ZTO/IZO) thin-film transistors. The field-effect mobility (MUFE) and
      photo-bias stability of the double-channel device were improved by increasing the
      thickness of the front IZO film (t(int)) compared to the single-ZTO-channel
      device. A high-mobility (approximately 32.3 cm(2)/Vs) ZTO/IZO transistor with
      excellent photo-bias stability was obtained from Sn doping of the front IZO
      layer. First-principles calculations revealed an increase in the formation energy
      of O vacancy defects in the Sn-doped IZO layer compared to the IZO layer. This
      observation suggests that the superior photo-bias stability of the double-channel
      device is due to the effect of Sn doping during thermal annealing. However, these
      improvements were observed only when t(int) was less than the critical thickness.
      The rationale for this observation is also discussed based on the oxygen vacancy
      defect model.

PMID- 24441829
TI  - Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty
      acids.
AB  - Fatty acids are integral mediators of energy storage, membrane formation and cell
      signaling. The pathways that orchestrate uptake of fatty acids remain
      incompletely understood. Expression of the integrin ligand Mfge8 is increased in
      human obesity and in mice on a high-fat diet, but its role in obesity is unknown.
      We show here that Mfge8 promotes the absorption of dietary triglycerides and the
      cellular uptake of fatty acid and that Mfge8-deficient (Mfge8(-/-)) mice are
      protected from diet-induced obesity, steatohepatitis and insulin resistance.
      Mechanistically, we found that Mfge8 coordinates fatty acid uptake through
      alphavbeta3 integrin- and alphavbeta5 integrin-dependent phosphorylation of Akt
      by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of
      Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our
      results imply a role for Mfge8 in regulating the absorption and storage of
      dietary fats, as well as in the development of obesity and its complications. 

PMID- 24441831
TI  - Mechanical interaction of angiogenic microvessels with the extracellular matrix.
AB  - Angiogenesis is the process by which new blood vessels sprout from existing blood
      vessels, enabling new vascular elements to be added to an existing vasculature.
      This review discusses our investigations into the role of cell-matrix mechanics
      in the mechanical regulation of angiogenesis. The experimental aspects of the
      research are based on in vitro experiments using an organ culture model of
      sprouting angiogenesis with the goal of developing new treatments and techniques
      to either promote or inhibit angiogenic outgrowth, depending on the application.
      Computational simulations were performed to simulate angiogenic growth coupled to
      matrix deformation, and live two-photon microscopy was used to obtain insight
      into the dynamic mechanical interaction between angiogenic neovessels and the
      extracellular matrix. In these studies, we characterized how angiogenic
      neovessels remodel the extracellular matrix (ECM) and how properties of the
      matrix such as density and boundary conditions influence vascular growth and
      alignment. Angiogenic neovessels extensively deform and remodel the matrix
      through a combination of applied traction, proteolytic activity, and generation
      of new cell-matrix adhesions. The angiogenic phenotype within endothelial cells
      is promoted by ECM deformation and remodeling. Sensitivity analysis using our
      finite element model of angiogenesis suggests that cell-generated traction during
      growth is the most important parameter controlling the deformation of the matrix
      and, therefore, angiogenic growth and remodeling. Live two-photon imaging has
      also revealed numerous neovessel behaviors during angiogenesis that are poorly
      understood such as episodic growth/regression, neovessel colocation, and
      anastomosis. Our research demonstrates that the topology of a resulting vascular
      network can be manipulated directly by modifying the mechanical interaction
      between angiogenic neovessels and the matrix. 

PMID- 24441832
TI  - Pricing Policies And Control of Tobacco in Europe (PPACTE) project: cross
      national comparison of smoking prevalence in 18 European countries.
AB  - Limited data on smoking prevalence allowing valid between-country comparison are
      available in Europe. The aim of this study is to provide data on smoking
      prevalence and its determinants in 18 European countries. In 2010, within the
      Pricing Policies And Control of Tobacco in Europe (PPACTE) project, we conducted
      a face-to-face survey on smoking in 18 European countries (Albania, Austria,
      Bulgaria, Czech Republic, Croatia, England, Finland, France, Greece, Hungary,
      Ireland, Italy, Latvia, Poland, Portugal, Romania, Spain and Sweden) on a total
      of 18 056 participants, representative for each country of the population aged 15
      years or older. Overall, 27.2% of the participants were current smokers (30.6% of
      men and 24.1% of women). Smoking prevalence was highest in Bulgaria (40.9%) and
      Greece (38.9%) and lowest in Italy (22.0%) and Sweden (16.3%). Smoking prevalence
      ranged between 15.7% (Sweden) and 44.3% (Bulgaria) for men and between 11.6%
      (Albania) and 38.1% (Ireland) for women. Multivariate analysis showed a
      significant inverse trend between smoking prevalence and the level of education
      in both sexes. Male-to-female smoking prevalence ratios ranged from 0.85 in Spain
      to 3.47 in Albania and current-to-ex prevalence ratios ranged from 0.68 in Sweden
      to 4.28 in Albania. There are considerable differences across Europe in smoking
      prevalence, and male-to-female and current-to-ex smoking prevalence ratios.
      Eastern European countries, lower income countries and those with less advanced
      tobacco control policies have less favourable smoking patterns and are at an
      earlier stage of the tobacco epidemic. 

PMID- 24441833
TI  - From the editor.

PMID- 24441834
TI  - Older workers.

PMID- 24441828
TI  - The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered
      arrhythmias.
AB  - Spontaneous Ca(2+) release from intracellular stores is important for various
      physiological and pathological processes. In cardiac muscle cells, spontaneous
      store overload-induced Ca(2+) release (SOICR) can result in Ca(2+) waves, a major
      cause of ventricular tachyarrhythmias (VTs) and sudden death. The molecular
      mechanism underlying SOICR has been a mystery for decades. Here we show that a
      point mutation, E4872A, in the helix bundle crossing region (the proposed gate)
      of the cardiac ryanodine receptor (RyR2) completely abolishes luminal, but not
      cytosolic, Ca(2+) activation of RyR2. The introduction of metal-binding
      histidines at this site converts RyR2 into a luminal Ni(2+)-gated channel. Mouse
      hearts harboring a heterozygous RyR2 mutation at this site (E4872Q) are resistant
      to SOICR and are completely protected against Ca(2+)-triggered VTs. These data
      show that the RyR2 gate directly senses luminal (store) Ca(2+), explaining the
      regulation of RyR2 by luminal Ca(2+), the initiation of Ca(2+) waves and Ca(2+)
      triggered arrhythmias. This newly identified store-sensing gate structure is
      conserved in all RyR and inositol 1,4,5-trisphosphate receptor isoforms. 

PMID- 24441835
TI  - An Aging Challenge for the NinetiesBalancing the Aging Process Against
      Experience.

PMID- 24441836
TI  - Considerations for the visually impaired older worker.

PMID- 24441837
TI  - The Older Worker and Incidence of InjuryTrends in Heavy Industry.

PMID- 24441838
TI  - Images of success among older workers in new jobs.

PMID- 24441839
TI  - Age Changes in the Older Adult WorkerImplications for Injury Prevention.

PMID- 24441841
TI  - Rehabilitating the older injured worker.

PMID- 24441840
TI  - Fatal farm injuries to older workers.

PMID- 24441842
TI  - More Than a Nine-to-Five JobIssues of the Employed Caregiver.

PMID- 24441843
TI  - The older worker and the system.
AB  - Most of us hold opinions on contemporary issues in work practice, in all its
      broad dimensions. Sounding Board is a regular feature of this publication,
      designed to provide a forum for expressing such views, whether mainstream or
      controversial.The opinions expressed in this section may not necessarily
      represent the views of the editor, the publisher, or the editorial board, but are
      intended to stimulate discussion or to provoke a response. Readers who wish to
      comment on the ideas put forth in Sounding Board should address their comments to
      the editor. 

PMID- 24441844
TI  - Work technology review.

PMID- 24441846
TI  - ["Extended suicide". Homicide-suicide under psychopathological and criminological
      aspects].
AB  - BACKGROUND: Homicide-suicide is a rare and serious phenomenon which mainly occurs
      in intimate relationships and families. MATERIALS AND METHODS: In this study ten
      cases of murder-suicide during the period 2006-2011 in the greater area of
      Dusseldorf were investigated. Data were obtained from coroner and prosecution
      files. RESULTS: All perpetrators were male. In accordance with the literature the
      results of the analysis revealed male sex, higher age, intimate partnership,
      access to firearms and special personality traits, mainly emotionally unstable,
      narcissistic traits and aggressiveness as the main risk factors. In all cases, at
      least three risk factors were identified. Breakdown of the marital relationship
      and social descent emerged as probable leading motives. Shooting was the most
      frequent method of killing followed by sharp force. CONCLUSIONS: Compared with
      homicide and suicide, homicide-suicide appears to be a distinct phenomenon. The
      knowledge and understanding of relevant risk factors could help mental health
      professionals, police and public authorities to intervene in time.

PMID- 24441847
TI  - [Oxidative stress in bipolar affective disorder].
AB  - The results of mortality studies have indicated that medical conditions, such as
      cardiovascular disease, obesity and diabetes are the most important causes of
      mortality among patients with bipolar disorder. The reasons for the increased
      incidence and mortality are not fully understood. Oxidative stress and an
      inadequate antioxidative system might be one missing link and could also help to
      further elucidate the pathophysiological basis of bipolar disorder. This article
      provides a comprehensive review of oxidative stress in general and about the
      existing data for bipolar disorder. In addition information is given about
      possible therapeutic strategies to reduce oxidative stress and the use in bipolar
      disorder. 

PMID- 24441849
TI  - From the editor.

PMID- 24441850
TI  - A review of the literature: Implementation and management of an on-site
      ergonomics program - the occupational therapist's role.
AB  - Cumulative trauma disorders (CTDs) are a major problem facing industry and
      workers today. A successful ergonomics program can be designed by the
      occupational therapist (OT) to meet the unique needs of a company. It can help
      manage costs and control CTDs. The successful implementation of an ergonomics
      program requires a team effort and must include management, engineers, line
      supervisors, workers and the health care provider with a knowledge of ergonomic
      principles. A well designed ergonomics program should include surveillance
      activities, worksite job analysis and education and training of all employees.
      Solutions to identified problems can be developed through administrative and
      engineering controls and modification of work practices. This article reviews the
      role of the OT in the implementation and management of an on-site ergonomics
      program. 

PMID- 24441848
TI  - [Peripheral nerve lesions of the lower leg due to tibiofibular ganglion].
AB  - Cystic formations around the knee are a common object of orthopedic treatment.
      When associated with neurological or vascular deficits further diagnostic imaging
      is required. This case study demonstrates the appearance of an intramuscular
      ganglion causing drop foot, arising from the tibio-fibular joint. 

PMID- 24441851
TI  - Challenges in occupational health towards the year 2000.
AB  - In order to identify the relevant challenges in occupational health in the next
      century, changes in demographic profile and work activity must first be
      considered. Only then can the challenges be identified, and appropriate
      strategies be formulated to respond to these challenges. In a newly
      industrializing country such as Singapore, improved work conditions; the advent
      of new technology; a redistribution of work activity (with a reduction of factory
      workers and an increase in service sector workers); and an ageing workforce can
      be expected. These changes, together with a possible increase of some types of
      work related disorders (such as cumulative trauma disorders, and disorders
      resulting from psychosocial hazards); will determine the relevant occupational
      health challenges to be faced. Added to this would be society's higher
      expectations for health care, a humane and compassionate health care, and an
      improved quality of life. As a result, what is needed in Singapore might be (1) a
      shift in the focus of current health care activities to pay sufficient attention
      to new hazards at work, and newly emerging work related diseases, (2) improved
      training and development of health professionals to better prepare them to face
      these changes, and (3) a responsive and appropriate legislation to protect the
      health of all workers. 

PMID- 24441852
TI  - Age-related overexertion injuries among Swedish nursing auxiliaries over a 10
      year period.
AB  - This study examines the age-related risk of overexertion injuries among Swedish
      nursing auxiliaries. Overexertion ratios (ORs) and injury severity were measured
      over time, for males and females separately, all injuries aggregated and for
      three injury patterns, employing five age categories and three time periods. OR
      values varied by time period, age and gender. The number of injuries by
      overexertion-injury pattern varied over time, and the ORs of particular age
      groups were related to pattern. Female auxiliaries aged 16-24 and 45-54, and also
      male auxiliaries aged 25-34 consistently showed ORs greater than 1.0. Injuries of
      all types tended to be more severe with increasing age. These findings provide
      grounds for reconsidering auxiliaries' occupational tasks and work aids, and
      methods for safety promotion. They suggest that preventive programs should be
      targeted so as to address several different overexertion-injury patterns,
      depending on age group and gender. 

PMID- 24441853
TI  - Work hardening in an early return to work program for nurses with back injury.
AB  - OBJECTIVES: Work assessment and work hardening were components of a comprehensive
      interdisciplinary program to prevent and manage back injury in nurses in a large
      tertiary care hospital. The effect of work hardening on morbidity and work status
      is described. STUDY DESIGN: Nurses injured on 'target' wards who had time loss
      exceeding four working days received a work assessment. RESULTS determined work
      placement: work hardening. modified work or return to regular work. Pain,
      disability and lifting tolerance were monitored during work hardening and
      modified work; pain, disability, work endurance and work status were compared
      between initial and follow-up assessments. RESULTS: Seven nurses received work
      hardening. All had increased lifting capacity; pain and disability scores
      decreased and, by 6 months follow-up, all were working full shifts at their
      regular jobs. CONCLUSION: RESULTS support the concept of maintaining individuals
      with back injury in the workplace by providing early, on-site intervention that
      includes work hardening and modified work.

PMID- 24441854
TI  - Evaluation of forearm fatigue during EVA pressure glove work.
AB  - This study investigated the combined use of three measurement techniques to
      monitor fatigue in forearm muscles during pressure glove work. Pressurized gloves
      are a component of the spacesuit used by shuttle astronauts during extravehicular
      activities (EVA). The study was conducted to specifically evaluate and compare
      the effects of pressure and non-pressure components of the glove on work and
      fatigue. Ten healthy male subjects were recruited to perform a constrained task
      of repetitively squeezing a custom hand-grip dynamometer adjusted for constant
      resistance. Surface electromyographic (EMG) signals from two muscles of the
      forearm (m. extensor carpi ulnaris (ECU) and m. flexor digitorum superficialis
      (FDS)) were recorded concurrently with mechanical work and subjective fatigue.
      Measurements were made before, during, and after the repetitive gripping task.
      Each subject performed the test under three conditions: (1) bare hand, (2) gloved
      hand without a pressure differential, and (3) gloved-hand with a pressure
      differential equal to the normal operating pressure of the shuttle glove. The
      results demonstrated that the three measurement procedures provided complementary
      information about the interrelationship between glove characteristics, muscle
      function, and work productivity. The EMG results from the FDS muscle indicated
      that the resistance offered by the glove materials provided a component of
      fatigue that was compounded by the presence of differential pressure. Although
      not muscle specific, measurements of work output and subjective fatigue supported
      this finding. In contrast to the FDS, the EMG results from the ECU muscle
      indicated that this muscle was less fatigued overall and less sensitive to the
      test conditions. Although high inter-subject variability precluded a
      statistically significant effect of test condition on the EMG results from the
      ECU muscle, 8 of the 10 subjects had higher EMG manifestations of fatigue for
      bare hand work than for either gloved-hand condition. We interpret these findings
      as evidence that the stiffness of the glove may have provided support to the
      wrist, thereby reducing the amount of fatigue present in this muscle during the
      work task. The study findings demonstrate the feasibility of using this
      multidimensional approach to fatigue measurement when evaluating other work
      related tasks. 

PMID- 24441855
TI  - The Skills and Employment Opportunities Project: report of an evaluation.
AB  - OBJECTIVES: the research was designed to evaluate the success of a Project set up
      to find employment or training in ordinary firms or organisations for people with
      disabilities. METHODS: three main sources of data were used: the Project's data
      base, which included information on client 'outcomes'; postal questionnaires and
      interviews with Project clients; postal questionnaire and interviews with
      referrers to the Project. RESULTS: the rate of referral to the Project vastly
      exceeded expectations. According to the Project's 'outcome' categories, 66% of
      the clients were successfully placed, and clients' accounts verified this. The
      expectations of referrers of people with learning disabilities for their clients
      exceeded 'outcomes' but referrers of people with physical disabilities under
      estimated them. Clients' views were generally favourable but they would have
      liked more choice and aspired to improving their work placements. CONCLUSIONS:
      The evidence indicated that the Project had a role in the area not filled by
      other agencies.

PMID- 24441856
TI  - Stimulating adult development in the workplace through critical thinking.
AB  - The workplace often requires the use of critical thinking which, in turn, may
      stimulate certain aspects of adult development. This article proposes several
      characteristics of critical thinking that may contribute to adult development as
      it occurs in the workplace. The concepts considered apply to managers and workers
      in a variety of situations. 

PMID- 24441857
TI  - Chronic illness and return to work: a social cognitive perspective.
AB  - High unemployment rates for people with multiple sclerosis are frequently
      attributed to decreases in self-efficacy and outcome expectations with respect to
      job seeking and retaining tasks. Hence, return-to-work interventions must enable
      people with MS to develop positive expectations. They must believe (a) that they
      possess the abilities needed to respond effectively in the job interview and
      request reasonable job accommodations (self-efficacy) and (b) that they will
      secure employment as a result of their efforts (outcome expectations). Based on
      social cognitive strategies, the Accommodations Planning Team (APT) Seminar
      offers the skill training required for increasing employment-related efficacy and
      outcome expectations. 

PMID- 24441858
TI  - The redeployment of blind and partially sighted staff in the banking industry.
AB  - UK banks have traditionally employed blind and partially sighted people as
      telephonists. The introduction of new technology and organisational restructuring
      has lead to a decrease in the need for clerical staff. Banks are faced with the
      dilemma of what to do with blind and partially sighted telephonists. Many are
      considering the options and preferring to deal with individual cases at a local
      level as they become pressing rather than take a co-ordinated approach. This
      paper describes how one Bank decided to tackle this challenge at a corporate
      level through a company wide redeployment project, assisted by the Royal National
      Institute for the Blind (RNIB). Data collection, assessments, job analysis and
      technical investigations are described. The central role of training both for
      project participants and personnel staff is discussed and the responsibilities of
      project Case Managers are reported. So far over 100 members of staff have been
      relocated, supplied with new equipment, had their current job expanded or been
      placed in a new job. Some other wide ranging results such as changes to Bank
      policy are discussed. The conclusion highlights some of the challenges
      encountered and suggests how the lessons learned through the project might be
      applied to other situations. 

PMID- 24441859
TI  - The occupational safety and health administration's role in ergonomics.
AB  - The Occupational Safety and Health Administration has developed a draft Ergonomic
      Protection Standard. The goal of having such a standard is to prevent work
      related musculoskeletal disorders or reduce the severity of such injuries. The
      guidelines address identification of problem jobs, control of risk factor
      exposures, ergonomic design, training and documentation. How businesses and
      employees will be affected if the draft becomes a guideline is addressed in this
      paper. Also addressed is the possible role that occupational therapists may play
      in ergonomics if such a guideline is implemented. 

PMID- 24441860
TI  - World population pressures.

PMID- 24441861
TI  - A client-centered ecological approach.

PMID- 24441862
TI  - Understanding the process of envelope glycoprotein incorporation into virions in
      simian and feline immunodeficiency viruses.
AB  - The lentiviral envelope glycoproteins (Env) mediate virus entry by interacting
      with specific receptors present at the cell surface, thereby determining viral
      tropism and pathogenesis. Therefore, Env incorporation into the virions formed by
      assembly of the viral Gag polyprotein at the plasma membrane of the infected
      cells is a key step in the replication cycle of lentiviruses. Besides being
      useful models of human immunodeficiency virus (HIV) infections in humans and
      valuable tools for developing AIDS therapies and vaccines, simian and feline
      immunodeficiency viruses (SIV and FIV, respectively) are relevant animal
      retroviruses; the study of which provides important information on how lentiviral
      replication strategies have evolved. In this review, we discuss the molecular
      mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into
      viral particles. 

PMID- 24441863
TI  - Structural and functional comparisons of retroviral envelope protein C-terminal
      domains: still much to learn.
AB  - Retroviruses are a family of viruses that cause a broad range of pathologies in
      animals and humans, from the apparently harmless, long-term genomic insertion of
      endogenous retroviruses, to tumors induced by the oncogenic retroviruses and
      acquired immunodeficiency syndrome (AIDS) resulting from human immunodeficiency
      virus infection. Disease can be the result of diverse mechanisms, including
      tumorigenesis induced by viral oncogenes or immune destruction, leading to the
      gradual loss of CD4 T-cells. Of the virally encoded proteins common to all
      retroviruses, the envelope (Env) displays perhaps the most diverse functionality.
      Env is primarily responsible for binding the cellular receptor and for effecting
      the fusion process, with these functions mediated by protein domains localized to
      the exterior of the virus. The remaining C-terminal domain may have the most
      variable functionality of all retroviral proteins. The C-terminal domains from
      three prototypical retroviruses are discussed, focusing on the different
      structures and functions, which include fusion activation, tumorigenesis and
      viral assembly and lifecycle influences. Despite these genetic and functional
      differences, however, the C-terminal domains of these viruses share a common
      feature in the modulation of Env ectodomain conformation. Despite their
      differences, perhaps each system still has information to share with the others. 

PMID- 24441865
TI  - Pharmacokinetic variability of amikacin after once-daily and twice-daily dosing
      regimen in full-term neonates.
AB  - The purpose of the study was to compare peak (Cpeak) and trough (Ctrough)
      amikacin levels after twice-daily (TD) or once-daily dosing (OD) in full-term
      neonates. Additionally, the study aimed to address amikacin pharmacokinetics and
      its variability. Data included 31 patients born on term. Amikacin daily dose was
      15 or 20 mg/kg depending on the neonate's age. Patients randomly received
      amikacin every 12 or 24 h. In all patients corresponding Cpeak and Ctrough were
      taken. Volume of distribution (Vd), clearance (CL) and half-life (t1/2) were
      calculated. Mean Cpeak of 21.79 MUg/ml in the TD group was statistically
      different from Cpeak of 36.39 MUg/ml in the OD group. Average Ctrough in TD (5.67
      MUg/ml) was statistically different from the corresponding 3.99 MUg/ml in the OD
      group. Mean amikacin Vd, CL, and t1/2 were 0.78 +/- 0.38 l/kg, 86.99 +/- 48.22
      ml/h?kg, and 6.81 +/- 2.51 h, respectively. High interindividual pharmacokinetic
      variability was observed. Further analysis showed that neonatal age contributed
      to the pharmacokinetic parameters' values. Statistically significant difference
      in CL and t1/2 was observed between patients age <= 2 and > 2 days on therapy
      initiation. As expected, amikacin given OD achieved higher Cpeak and lower
      Ctrough than TD. Based on the results, observed variability in amikacin
      pharmacokinetics was possibly due to the renal maturation process.

PMID- 24441866
TI  - Life cycle assessment of CO2 capture and utilization: a tutorial review.
AB  - Capturing CO2 and using it as an alternative carbon feedstock for chemicals,
      fuels and materials has the potential to reduce both CO2 emissions and fossil
      resource depletion. To assess the actual environmental benefits of CO2 capture
      and utilization (CCU), life cycle assessment (LCA) is considered as suitable
      metric. To enhance the use of LCA of CCU, this tutorial review gives a jargon
      free introduction of LCA of CCU directed at LCA novices. Nine particularly
      important aspects for conducting an LCA of CCU are identified and illustrated
      with CCU examples. These aspects, phrased as action items, can serve LCA novices
      as a checklist through all steps in LCA of CCU: from defining the LCA purpose and
      the system boundaries, over data collection and environmental impact computation,
      to interpretation and sensitivity analysis of the results. Finally, in the
      context of CCU, an outlook is given on recent developments in LCA that aim to
      cover all pillars of sustainability (people, planet, and profit). 

PMID- 24441864
TI  - Mitochondrial activity, hemocyte parameters and lipid composition modulation by
      dietary conditioning in the Pacific oyster Crassostrea gigas.
AB  - Several parameters can affect membrane lipid composition in bivalves, including
      diet. Although two fatty acids (FA) 22:6n-3 and 20:5n-3 are essential membrane
      components, they are sparingly synthesized by bivalves and must be obtained from
      their diet. Here, effects of dietary modifications of membrane lipid composition
      were studied at both cellular and subcellular levels in the oyster Crassostrea
      gigas. To this end, we compared oysters fed two monoalgal diets that differed
      markedly in their FA composition and a mix of both. As expected, algae impacted
      phospholipids, in particular 22:6n-3 and 20:5n-3, reflecting differences of
      dietary microalgae FA composition. Meantime, total saturated FA, total
      monounsaturated FA, total polyunsaturated FA and total non-methylene-interrupted
      FA varied little and phospholipid class composition was only slightly affected by
      diets. Measures made in hemocytes indicated that only mitochondrial membrane
      potential was affected by diets. Total ROS production as well as mitochondrial
      superoxide production did not differ with diet. There was no difference in
      phosphorylating (state 3) and non-phosphorylating (state 4) rates of oxygen
      consumption rates or in cytochrome c oxidase activity of mitochondria isolated
      from gills between the three diets. Similarly, neither cytochromes a, b, c or c1
      content nor citrate synthase activities were changed, suggesting that number and
      morphology of mitochondria were not affected by dietary treatment. These results
      suggest that oysters could possess high homeostatic capabilities, at both
      cellular and subcellular levels, to minimize the effect of dietary FA and related
      membrane lipid FA modifications on mitochondrial functions. These capabilities
      could be a means to face variations in diet composition in their natural
      environment and to preserve important oyster physiological functions such as
      growth and reproduction.

PMID- 24441867
TI  - Radon, the lognormal distribution and deviation from it.
AB  - It has been recognised for many years that the distributions of indoor radon
      concentrations in many countries conform more or less closely to a lognormal
      distribution. For homes situated over a single geological unit with a consistent
      source of radon in the ground, conformance with the lognormal distribution can be
      understood in terms of the multiplicative factors affecting the relationship
      between radium in the ground and radon in indoor air. The fact that national as
      well as local distributions of indoor radon also usually conform to the lognormal
      can be attributed to the fact that the mixture of a number of different lognormal
      distributions will often result in a lognormal distribution. In some cases,
      however, the national distributions of indoor radon deviate from a lognormal
      distribution: the reasons for this are examined using model normal distributions.
      A study of the deviation of the UK distribution from log-normality above 500 Bq
      m(-3) provides a better estimate of the number of homes with very high radon
      concentrations. 

PMID- 24441869
TI  - Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts.
AB  - MicroRNAs are small noncoding RNAs that inhibit protein expression. We have
      previously shown that the inhibition of the microRNA let-7d in epithelial cells
      caused changes consistent with epithelial-to-mesenchymal transition (EMT) both in
      vitro and in vivo. The aim of this study was to determine whether the
      introduction of let-7d into fibroblasts alters their mesenchymal properties.
      Transfection of primary fibroblasts with let-7d caused a decrease in expression
      of the mesenchymal markers alpha-smooth muscle actin, N-cadherin, fibroblast
      specific protein-1, and fibronectin, as well as an increase in the epithelial
      markers tight junction protein-1 and keratin 19. Phenotypic changes were also
      present, including a delay in wound healing, reduced motility, and proliferation
      of fibroblasts following transfection. In addition, we examined the effects of
      transfection on fibroblast responsiveness to TGF-beta, an important factor in
      many fibrotic processes such as lung fibrosis and found that let-7d transfection
      significantly attenuated high-mobility group-A2 protein induction by TGF-beta.
      Our results indicate that administration of the epithelial microRNA let-7d can
      significantly alter the phenotype of primary fibroblasts. 

PMID- 24441870
TI  - TNF-alpha induces cytosolic phospholipase A2 expression via Jak2/PDGFR-dependent
      Elk-1/p300 activation in human lung epithelial cells.
AB  - Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist
      induced arachidonic acid release for prostaglandin (PG) synthesis during
      inflammation triggered by tumor necrosis factor-alpha (TNF-alpha). However, the
      mechanisms underlying TNF-alpha-induced cPLA2 expression in human lung epithelial
      cells (HPAEpiCs) were not completely understood. Here, we demonstrated that TNF
      alpha induced cPLA2 mRNA and protein expression, promoter activity, and PGE2
      secretion in HPAEpiCs. These responses induced by TNF-alpha were inhibited by
      pretreatment with the inhibitor of Jak2 (AG490), platelet-derived growth factor
      receptor (PDGFR) (AG1296), phosphoinositide 3 kinase (PI3K) (LY294002), or MEK1/2
      (PD98059) and transfection with siRNA of Jak2, PDGFR, Akt, or p42. We showed that
      TNF-alpha markedly stimulated Jak2, PDGFR, Akt, and p42/p44 MAPK phosphorylation,
      which were attenuated by their respective inhibitors. Moreover, TNF-alpha
      stimulated Akt activation via a Jak2/PDGFR pathway in HPAEpiCs. In addition, TNF
      alpha-induced p42/p44 MAPK phosphorylation was reduced by AG1296 or LY294002. On
      the other hand, TNF-alpha could induce Akt and p42/p44 MAPK translocation from
      the cytosol into the nucleus, which was inhibited by AG490, AG1296, or LY294002.
      Finally, we showed that TNF-alpha stimulated Elk-1 phosphorylation, which was
      reduced by LY294002 or PD98059. We also observed that TNF-alpha time dependently
      induced p300/Elk-1 and p300/Akt complex formation in HPAEpiCs, which was reduced
      by AG490, AG1296, or LY294002. The activity of cPLA2 protein upregulated by TNF
      alpha was reflected on the PGE2 release, which was reduced by AG490, AG1296,
      LY294002, or PD98059. Taken together, these results demonstrated that TNF-alpha
      induced cPLA2 expression and PGE2 release were mediated through a
      Jak2/PDGFR/PI3K/Akt/p42/p44 MAPK/Elk-1 pathway in HPAEpiCs. 

PMID- 24441868
TI  - Glutathione attenuates ethanol-induced alveolar macrophage oxidative stress and
      dysfunction by downregulating NADPH oxidases.
AB  - Chronic alcohol abuse increases lung oxidative stress and susceptibility to
      respiratory infections by impairing alveolar macrophage (AM) function. NADPH
      oxidases (Nox) are major sources of reactive oxygen species in AMs. We
      hypothesized that treatment with the critical antioxidant glutathione (GSH)
      attenuates chronic alcohol-induced oxidative stress by downregulating Noxes and
      restores AM phagocytic function. Bronchoalveolar lavage (BAL) fluid and AMs were
      isolated from male C57BL/6J mice (8-10 wk) treated +/- ethanol in drinking water
      (20% wt/vol, 12 wk) +/- orally gavaged GSH in methylcellulose vehicle (300 mg x
      kg(-1) x day(-1), during week 12). MH-S cells, a mouse AM cell line, were treated
      +/- ethanol (0.08%, 3 days) +/- GSH (500 MUM, 3 days or last 1 day of ethanol).
      BAL and AMs were also isolated from ethanol-fed and control mice +/- inoculated
      airway Klebsiella pneumoniae (200 colony-forming units, 28 h) +/- orally gavaged
      GSH (300 mg/kg, 24 h). GSH levels (HPLC), Nox mRNA (quantitative RT-PCR) and
      protein levels (Western blot and immunostaining), oxidative stress (2',7'
      dichlorofluorescein-diacetate and Amplex Red), and phagocytosis (Staphylococcus
      aureus internalization) were measured. Chronic alcohol decreased GSH levels,
      increased Nox expression and activity, enhanced oxidative stress, impaired
      phagocytic function in AMs in vivo and in vitro, and exacerbated K. pneumonia
      induced oxidative stress. Although how oral GSH restored GSH pools in ethanol-fed
      mice is unknown, oral GSH treatments abrogated the detrimental effects of chronic
      alcohol exposure and improved AM function. These studies provide GSH as a novel
      therapeutic approach for attenuating alcohol-induced derangements in AM Nox
      expression, oxidative stress, dysfunction, and risk for pneumonia.

PMID- 24441871
TI  - KCNQ (Kv7) potassium channel activators as bronchodilators: combination with a
      beta2-adrenergic agonist enhances relaxation of rat airways.
AB  - KCNQ (Kv7 family) potassium (K(+)) channels were recently found in airway smooth
      muscle cells (ASMCs) from rodent and human bronchioles. In the present study, we
      evaluated expression of KCNQ channels and their role in constriction/relaxation
      of rat airways. Real-time RT-PCR analysis revealed expression of KCNQ4 > KCNQ5 >
      KCNQ1 > KCNQ2 > KCNQ3, and patch-clamp electrophysiology detected KCNQ currents
      in rat ASMCs. In precision-cut lung slices, the KCNQ channel activator retigabine
      induced a concentration-dependent relaxation of small bronchioles preconstricted
      with methacholine (MeCh; EC50 = 3.6 +/- 0.3 MUM). Bronchoconstriction was also
      attenuated in the presence of two other structurally unrelated KCNQ channel
      activators: zinc pyrithione (ZnPyr; 1 MUM; 22 +/- 7%) and 2,5-dimethylcelecoxib
      (10 MUM; 24 +/- 8%). The same three KCNQ channel activators increased KCNQ
      currents in ASMCs by two- to threefold. The bronchorelaxant effects of retigabine
      and ZnPyr were prevented by inclusion of the KCNQ channel blocker XE991. A long
      acting beta2-adrenergic receptor agonist, formoterol (10 nM), did not increase
      KCNQ current amplitude in ASMCs, but formoterol (1-1,000 nM) did induce a time-
      and concentration-dependent relaxation of rat airways, with a notable
      desensitization during a 30-min treatment or with repetitive treatments.
      Coadministration of retigabine (10 MUM) with formoterol produced a greater peak
      and sustained reduction of MeCh-induced bronchoconstriction and reduced the
      apparent desensitization observed with formoterol alone. Our findings support a
      role for KCNQ K(+) channels in the regulation of airway diameter. A combination
      of a beta2-adrenergic receptor agonist with a KCNQ channel activator may improve
      bronchodilator therapy. 

PMID- 24441874
TI  - Frequency tracking in acoustic trapping for improved performance stability and
      system surveillance.
AB  - This work proposes and demonstrates an acoustic trapping system where the
      trapping frequency is automatically determined and can be used to analyse changes
      in the acoustic trap. Critical for the functionality of this system is the use of
      a kerfed transducer that removes spurious resonances. This makes it possible to
      determine the optimal trapping frequency by analysing electrical impedance. It is
      demonstrated that the novel combination of a kerfed transducer and acoustic
      trapping in glass capillaries creates a high Q-value resonator. This narrows the
      frequency bandwidth but allows excellent performance, as confirmed by a ten-fold
      increase in the flow retention speed when compared to previously reported values.
      Importantly, the use of automatic frequency tracking allows the use of such a
      narrow bandwidth resonator without compromising system stability. As changes in
      temperature, buffer-properties, and the amount of captured particles will affect
      the properties of the acoustic resonator, corresponding changes in resonance
      frequency will occur. It is shown that such frequency changes can be accurately
      tracked using the setup. Therefore, monitoring the frequency over time adds a new
      feature to acoustic trapping, where experimental progress can be monitored and
      the amount of trapped material can be quantified. 

PMID- 24441873
TI  - Loss of caveolin-1 and adiponectin induces severe inflammatory lung injury
      following LPS challenge through excessive oxidative/nitrative stress.
AB  - Excessive reactive oxygen/nitrogen species have been associated with the onset,
      progression, and outcome of sepsis, both in preclinical and clinical studies.
      However, the signaling pathways regulating oxidative/nitrative stress in the
      pathogenesis of sepsis-induced acute lung injury and acute respiratory distress
      syndrome are not fully understood. Employing the novel mouse model with genetic
      deletions of both caveolin-1 (Cav1) and adiponectin (ADPN) [double knockout (DKO)
      mice], we have demonstrated the critical role of Cav1 and ADPN signaling cross
      talk in regulating oxidative/nitrative stress and resulting inflammatory lung
      injury following LPS challenge. In contrast to the inhibited inflammatory lung
      injury in Cav1(-/-) mice, we observed severe lung inflammation and markedly
      increased lung vascular permeability in DKO mice in response to LPS challenge.
      Accordingly, the DKO mice exhibited an 80% mortality rate following a sublethal
      dose of LPS challenge. At basal state, loss of Cav1 and ADPN resulted in a
      drastic increase of oxidative stress and resultant nitrative stress in DKO lungs.
      Scavenging of superoxide by pretreating the DKO mice with MnTMPYP (a superoxide
      dismutase mimetic) restored the inflammatory responses to LPS challenge including
      reduced lung myeloperoxidase activity and vascular permeability. Thus
      oxidative/nitrative stress collectively modulated by Cav1 and ADPN signalings is
      a critical determinant of inflammatory lung injury in response to LPS challenge. 

PMID- 24441872
TI  - Macrophage migration inhibitory factor deficiency in chronic obstructive
      pulmonary disease.
AB  - The pathogenesis of chronic obstructive pulmonary disease (COPD) remains poorly
      understood. Cellular senescence and apoptosis contribute to the development of
      COPD; however, crucial regulators of these underlying mechanisms remain unknown.
      Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that
      antagonizes both apoptosis and premature senescence and may be important in the
      pathogenesis of COPD. This study examines the role of MIF in the pathogenesis of
      COPD. Mice deficient in MIF (Mif(-/-)) or the MIF receptor CD74 (Cd74(-/-)) and
      wild-type (WT) controls were aged for 6 mo. Both Mif(-/-) and Cd74(-/-) mice
      developed spontaneous emphysema by 6 mo of age compared with WT mice as measured
      by lung volume and chord length. This was associated with activation of the
      senescent pathway markers p53/21 and p16. Following exposure to cigarette smoke,
      Mif(-/-) mice were more susceptible to the development of COPD and apoptosis
      compared with WT mice. MIF plasma concentrations were measured in a cohort of 224
      human participants. Within a subgroup of older current and former smokers (n =
      72), MIF concentrations were significantly lower in those with COPD [8.8, 95%CI
      (6.7-11.0)] compared with those who did not exhibit COPD [12.7 ng/ml, 95%CI (10.6
      14.8)]. Our results suggest that both MIF and the MIF receptor CD74 are required
      for maintenance of normal alveolar structure in mice and that decreases in MIF
      are associated with COPD in human subjects. 

PMID- 24441875
TI  - Hybrid optical imaging technology for long-term remote monitoring of skin
      perfusion and temperature behavior.
AB  - Photoplethysmography imaging (PPGI) and infrared thermography imaging (IRTI) are
      contactless camera-based measurement methods for monitoring a wide range of basic
      vital parameters. In particular, PPGI enhances the classical contact-based
      photoplethysmography. Approved evaluation algorithms of the well-established PPG
      method can easily be adapted for detection of heart rate, heart rate variability,
      respiration rate (RR), respiratory variability (RV), and vasomotional activity
      with PPGI. The IRTI method primarily records temperature distribution of the
      observed object, but information on RR and RV can also be derived from IRTI by
      analyzing the development of temperature distribution in the nasal region. The
      main advantages of both monitoring methods are unobtrusive data acquisition and
      the possibility of assessing spatial assignment between vital parameters and body
      region. Hence, these methods enable long-term monitoring or the monitoring of
      effects with special local characteristics. Because the two systems supplement
      each, a combined hybrid application is proposed and its feasibility discussed.

PMID- 24441876
TI  - Shear wave pulse compression for dynamic elastography using phase-sensitive
      optical coherence tomography.
AB  - Assessing the biomechanical properties of soft tissue provides clinically
      valuable information to supplement conventional structural imaging. In the
      previous studies, we introduced a dynamic elastography technique based on phase
      sensitive optical coherence tomography (PhS-OCT) to characterize submillimetric
      structures such as skin layers or ocular tissues. Here, we propose to implement a
      pulse compression technique for shear wave elastography. We performed shear wave
      pulse compression in tissue-mimicking phantoms. Using a mechanical actuator to
      generate broadband frequency-modulated vibrations (1 to 5 kHz), induced
      displacements were detected at an equivalent frame rate of 47 kHz using a PhS
      OCT. The recorded signal was digitally compressed to a broadband pulse. Stiffness
      maps were then reconstructed from spatially localized estimates of the local
      shear wave speed. We demonstrate that a simple pulse compression scheme can
      increase shear wave detection signal-to-noise ratio (>12  dB gain) and reduce
      artifacts in reconstructing stiffness maps of heterogeneous media.

PMID- 24441877
TI  - Lateral and axial measurement differences between spectral-domain optical
      coherence tomography systems.
AB  - We assessed the reproducibility of lateral and axial measurements performed with
      spectral-domain optical coherence tomography (SDOCT) instruments from a single
      manufacturer and across several manufacturers. One human retina phantom was
      imaged on two instruments each from four SDOCT platforms: Zeiss Cirrus,
      Heidelberg Spectralis, Bioptigen SDOIS, and hand-held Bioptigen Envisu. Built-in
      software calipers were used to perform manual measurements of a fixed lateral
      width (LW), central foveal thickness (CFT), and parafoveal thickness (PFT) 1 mm
      from foveal center. Inter- and intraplatform reproducibilities were assessed with
      analysis of variance and Tukey-Kramer tests. The range of measurements between
      platforms was 5171 to 5290 MUm for mean LW (p<0.001), 162 to 196 MUm for mean CFT
      (p<0.001), and 267 to 316 MUm for mean PFT (p<0.001). All SDOCT platforms had
      significant differences between each other for all measurements, except LW
      between Bioptigen SDOIS and Envisu (p=0.27). Intraplatform differences were
      significantly smaller than interplatform differences for LW (p=0.020), CFT
      (p=0.045), and PFT (p=0.004). Conversion factors were generated for lateral and
      axial scaling between SDOCT platforms. Lateral and axial manual measurements have
      greater variance across different SDOCT platforms than between instruments from
      the same platform. Conversion factors for measurements from different platforms
      can produce normalized values for patient care and clinical studies.

PMID- 24441878
TI  - Age-dependent postoperative cognitive impairment and Alzheimer-related
      neuropathology in mice.
AB  - Post-operative cognitive dysfunction (POCD) is associated with increased cost of
      care, morbidity, and mortality. However, its pathogenesis remains largely to be
      determined. Specifically, it is unknown why elderly patients are more likely to
      develop POCD and whether POCD is dependent on general anesthesia. We therefore
      set out to investigate the effects of peripheral surgery on the cognition and
      Alzheimer-related neuropathology in mice with different ages. Abdominal surgery
      under local anesthesia was established in the mice. The surgery induced post
      operative elevation in brain beta-amyloid (Abeta) levels and cognitive impairment
      in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic
      mice, but not the 9 month-old wild-type mice. The Abeta accumulation likely
      resulted from elevation of beta-site amyloid precursor protein cleaving enzyme
      and phosphorylated eukaryotic translation initiation factor 2alpha. gamma
      Secretase inhibitor compound E ameliorated the surgery-induced brain Abeta
      accumulation and cognitive impairment in the 18 month-old mice. These data
      suggested that the peripheral surgery was able to induce cognitive impairment
      independent of general anesthesia, and that the combination of peripheral surgery
      with aging- or Alzheimer gene mutation-associated Abeta accumulation was needed
      for the POCD to occur. These findings would likely promote more research to
      investigate the pathogenesis of POCD. 

PMID- 24441879
TI  - Immunoactive two-dimensional self-assembly of monoclonal antibodies in aqueous
      solution revealed by atomic force microscopy.
AB  - The conformational flexibility of antibodies in solution directly affects their
      immune function. Namely, the flexible hinge regions of immunoglobulin G (IgG)
      antibodies are essential in epitope-specific antigen recognition and biological
      effector function. The antibody structure, which is strongly related to its
      functions, has been partially revealed by electron microscopy and X-ray
      crystallography, but only under non-physiological conditions. Here we observed
      monoclonal IgG antibodies in aqueous solution by high-resolution frequency
      modulation atomic force microscopy (FM-AFM). We found that monoclonal antibodies
      self-assemble into hexamers, which form two-dimensional crystals in aqueous
      solution. Furthermore, by directly observing antibody-antigen interactions using
      FM-AFM, we revealed that IgG molecules in the crystal retain immunoactivity. As
      the self-assembled monolayer crystal of antibodies retains immunoactivity at a
      neutral pH and is functionally stable at a wide range of pH and temperature, the
      antibody crystal is applicable to new biotechnological platforms for biosensors
      or bioassays. 

PMID- 24441881
TI  - [Sleep].

PMID- 24441880
TI  - Transformation of taxol-stabilized microtubules into inverted tubulin tubules
      triggered by a tubulin conformation switch.
AB  - Bundles of taxol-stabilized microtubules (MTs)--hollow tubules comprised of
      assembled alphabeta-tubulin heterodimers--spontaneously assemble above a critical
      concentration of tetravalent spermine and are stable over long times at room
      temperature. Here we report that at concentrations of spermine several-fold
      higher the MT bundles (B(MT)) quickly become unstable and undergo a shape
      transformation to bundles of inverted tubulin tubules (B(ITT)), the outside
      surface of which corresponds to the inner surface of the B(MT) tubules. Using
      transmission electron microscopy and synchrotron small-angle X-ray scattering, we
      quantitatively determined both the nature of the B(MT)-to-B(ITT) transformation
      pathway, which results from a spermine-triggered conformation switch from
      straight to curved in the constituent taxol-stabilized tubulin oligomers, and the
      structure of the B(ITT) phase, which is formed of tubules of helical tubulin
      oligomers. Inverted tubulin tubules provide a platform for studies requiring
      exposure and availability of the inside, luminal surface of MTs to MT-targeted
      drugs and MT-associated proteins.

PMID- 24441882
TI  - [Mental disorders in the general population : Study on the health of adults in
      Germany and the additional module mental health (DEGS1-MH)].
AB  - BACKGROUND AND OBJECTIVES: The German health interview and examination survey for
      adults (DEGS1) with the mental health module (DEGS1-MH) is the successor to the
      last survey of mental disorders in the general German population 15 years ago
      (GHS-MHS). This paper reports the basic findings on the 12-month prevalence of
      mental disorders, associated disabilities and self-reported healthcare
      utilization. METHODS: A representative national cohort (age range 18-79 years, n
      = 5,317) was selected and individuals were personally examined (87.5 % face to
      face and 12.5 % via telephone) by a comprehensive clinical interview using the
      composite international diagnostic interview (CIDI) questionnaire. RESULTS: The
      overall 12-month prevalence of mental disorders was 27.7 % with substantial
      differences between subgroups (e.g. sex, age, socioeconomic status). Mental
      disorders were found to be particularly impairing (elevated number of disability
      days). Less than 50 % of those affected reported to be in contact with health
      services due to mental health problems within the last 12 months (range 10-40 %
      depending on the number of diagnoses). CONCLUSIONS: Mental disorders were found
      to be commonplace with a prevalence level comparable to that found in the 1998
      predecessor study but several further adjustments will have to be made for a
      sound methodological comparison between the studies. Apart from individual
      distress, elevated self-reported disability indicated a high societal disease
      burden of mental disorders (also in comparison with many somatic diseases).
      Despite a relatively comprehensive and well developed mental healthcare system in
      Germany there are still optimisation needs for treatment rates.

PMID- 24441884
TI  - Direct ultrasound methods: a confirmatory technique for proper endotracheal
      intubation in the emergency department.
AB  - BACKGROUND AND OBJECTIVE: Early confirmation of incorrect endotracheal tube (ETT)
      placement is of vital importance when performing emergency airway management. No
      ideal confirmation technique has been proposed under all circumstances. Recently,
      ultrasonography was suggested as a useful tool for confirmation of correct
      positioning of the ETT. The aim of this study is to assess the diagnostic
      accuracy of ultrasonography for detection of proper ETT placement. MATERIALS AND
      METHODS: This prospective study was carried out in the emergency department from
      February to October 2012. The ultrasonography was performed by a trained senior
      resident in two phases: (a) as the intubation was being performed (dynamic phase)
      and (b) after the intubation had been completed (static phase). A linear probe
      was placed transversely over the cricothyroid membrane during the intubation
      process (dynamic phase) and on the anterior neck just superior to the
      suprasternal notch in the static method. Operating characteristics were
      calculated for both dynamic and static determination of ETT placement. RESULTS:
      Sixty patients were enrolled in each study group. The sensitivity, specificity,
      positive predictive value, and negative predictive value of the dynamic technique
      for determining correct endotracheal intubation were 98.1% [95% confidence
      interval (CI), 88.8-99.9%], 100% (95% CI, 51.6-100%), 100% (95% CI, 91.5-100%),
      and 85.7% (95% CI, 42-99.2%), respectively. Using the static technique, all
      testing characteristics listed previously were 100%. CONCLUSION: In this study,
      we found acceptable sensitivity, specificity, positive predictive value, and
      negative predictive value for prediction of tracheal ETT placement with the use
      of dynamic and static ultrasonography.

PMID- 24441885
TI  - From the editor.

PMID- 24441883
TI  - Tomographic comparison of cone-rod and rod-cone retinal dystrophies.
AB  - PURPOSE: To investigate the relationship between impairment of cone/rod
      photoreceptors and changes in optical coherence tomography (OCT) findings.
      METHODS: We retrospectively reviewed the clinical records of 35 patients with
      cone-rod dystrophy (CRD) and 35 visual acuity-matched patients with retinitis
      pigmentosa (RP). The presence or absence of the external limiting membrane (ELM),
      inner segment ellipsoid (ISe), interdigitation zone (IZ), and foveal cavitation
      (hyporeflective space in the outer retina) were determined using OCT image
      evaluation. RESULTS: There were no statistical differences in the number of CRD
      and RP patients with an intact ELM and ISe. None of the CRD patients had an
      intact IZ, but 20 % of RP patients did (P = 0.011). In addition, foveal
      cavitation tended to be observed more frequently in CRD patients than (25.7 %) in
      RP patients (5.7 %) despite the difference not being significant after the
      correction of multiple comparison. CONCLUSIONS: Eyes with CRD and RP had
      significant differences in foveal morphology, even when visual acuity was
      matched. This result supports the notion that absence of an IZ and the presence
      of foveal cavitation is related to cone-dominant photoreceptor impairment.

PMID- 24441886
TI  - Starting a driver rehabilitation program.
AB  - Driver rehabilitation programs assist clients in restoring transportation
      independence. This paper explores the many factors that a facility must consider
      when contemplating the provision of driver rehabilitation services. Topics
      include estimating market demand, preliminary research, staff credentialing,
      costs, funding and program models. Program implementation issues include policy
      development, vehicle selection, adapted equipment installation and program
      evaluation. Marketing strategies and liability issues are explored to highlight
      the rewards and risks that come with providing this specialty service. 

PMID- 24441887
TI  - The team approach to transportation assessment.
AB  - Driving and/or transportation is an activity of daily living that should be
      considered in the rehabilitation plan of any individual. Safe and reliable
      transportation can be one of the most important factors to ensure the complete
      rehabilitation of an individual no matter the age or condition. Evaluation of a
      person's transportation needs can be complex and should be performed by a
      qualified professional with the necessary medical background and specialty
      experience to adequately address the exact needs. This paper describes the role
      of the transportation team and the vital activity performed by a driver
      rehabilitation specialist during a comprehensive transportation assessment. 

PMID- 24441888
TI  - Good driving skills: implications for assessment and training.
AB  - The objective of this paper is to provide a conceptual framework for delineating
      the basic skills necessary for driving. It begins with a summary of existing
      theories of driving behavior. Next, it describes a common driving situation using
      theoretical concepts. It then provides a summary of expert opinion, focusing on
      awareness as the central component of good driving. The ideas presented
      throughout the paper are then integrated and, used to define a set of skills and
      abilities necessary for driving. Finally, two broad implications for developing
      driver assessment and training programs are presented. 

PMID- 24441889
TI  - Physical disabilities and their implications driving.
AB  - A brief overview of a variety of physical disabilities categorized as brain
      injured and non-brain injured are presented as they relate to independent
      driving. Adaptive driving aids, and driving systems as well as financial
      considerations and the role of the driver rehabilitation specialist in providing
      comprehensive driver assessments are discussed. A case study is included to
      demonstrate range of available driving equipment for persons with severe
      disabilities. 

PMID- 24441890
TI  - Crash survivors experiences.
AB  - The author hypothesized that survivors and families/friends of deceased victims
      of motor vehicle crashes experience their trauma in isolation, similar to victims
      of other types of violence and that non-alcohol related causes of crashes are
      poorly understood in our society. Outreach to survivors/family/friends of
      deceased victims through media and community events which focused on preventing
      crashes while remembering victims of prior crashes are described. Findings that
      post traumatic stress disorder symptoms are reported by all
      survivors/family/friends and experienced vicariously by emergency personnel and
      others indicate that this issue requires more attention by media and health care
      providers. Occupational therapists' expertise is critical in the process of the
      healing span and prevention of motor vehicle crashes through the media and
      memorial/educational community events. 

PMID- 24441891
TI  - Transport technology: New Zealand perspectives.
AB  - This article reviews the current driver and passenger assessment and
      rehabilitation in New Zealand with emphasis on those with an acquired disability.
      At the same time, heightened expectations by people with disabilities to achieve
      improved quality of life have also created a consumer driven demand for services.
      Established services have developed close team work between Occupational
      Therapists and Engineers, specialising in vehicle modifications for people with
      disabilities, who work together with the client to find the most ideal solution.
      Finally, this paper provides a description of a private practice in occupational
      therapy. As a case example, the Driver Assessment Service specialises wholly in
      assessing and meeting the transportation needs of people with disabilities and
      their funding agents. 

PMID- 24441892
TI  - The use of participation-oriented education in the rehabilitation of driving
      skills in older adults.
AB  - The driving abilities of adults appear to diminish in conjunction with age
      related physical and cognitive changes. In this exploratory study, rehabilitation
      strategies used with 21 older adults were examined to determine the most
      effective method of retraining driving skills. Subjects, who met the study's
      eligibility criteria (aged 55 years or older, held a valid driver's license,
      drove a minimum of 1000 miles/year, and no participation in an adult re-education
      program) received driver simulation training, classroom viewing of driver
      simulation films, or no treatment. Outcome measures included on-road and clinical
      evaluations, as well as self-report information. A significant difference was
      found between treatment type and subjects' accuracy scores for on-road
      evaluation, thus suggesting that driving simulation may result in a significant
      improvement in older adults' driving performance as compared to other
      intervention strategies. The study has particular relevance to occupational
      therapy practitioners, with their growing involvement in driving programs
      throughout the United States. 

PMID- 24441893
TI  - Researchers and occupational therapists can help each other to better understand
      what makes a good driver: two perspectives.

PMID- 24441894
TI  - Anti-personnel landmine injuries: a global epidemic.
AB  - Injuries and fatalities caused by anti-personnel landmines have become a global
      epidemic. Over 250 000 people alive today have been injured by landmines, many of
      whom required amputations. Civilians, including a large percentage of women and
      children, are injured at least as frequently as are military personnel. An
      estimated 10 000-100 000 additional people are killed or injured by landmines
      each year. There are presently in excess of 100 million active landmines buried
      or scattered throughout the world, and every day, an additional 5000 are put in
      place. The majority are in poor, underdeveloped, war-torn countries whose
      populations are already traumatized by conflict. At the cost of $300-000 per
      mine, the governments of these countries can not afford the process of de-mining
      their land, nor can they provide adequate emergency medical care and
      rehabilitation for landmine victims. The presence of mines in agricultural
      fields, near water supplies, along roadways and around villages, prevents the use
      of these essential resources, severely impacting on economic development. Health
      professionals are urged to support national and international legislation to
      completely ban the manufacture, sale and use of anti-personnel landmines. 

PMID- 24441895
TI  - Confirming job relatedness of symptoms: Secretary of Labor vs. Beverly
      Enterprises, Inc.

PMID- 24441897
TI  - Author indexVolume 8 (1997).

PMID- 24441896
TI  - Employment of individuals with deaf-blindness: Necessary skills and prevocational
      assessments.
AB  - The purpose of this paper is to discuss skills necessary for individuals with
      deaf-blindness to attain and retain employment, as well as identify prevocational
      assessments for this population. Activities of daily living including functional
      communication, socialization, and mobility are examined as necessary skills in
      relation to employment. Reasonable accommodations which promote better
      communication, socialization, and mobility for individuals with deaf-blindness in
      the work place are discussed. A case study is included to illustrate successful
      employment of an individual with deaf-blindness through the evaluation and
      assessment of necessary skills and personal interests, accompanied by reasonable
      accommodations. Due to the low incidence of this disorder, an introduction to the
      etiology and demographics of deaf-blindness is also provided. 

PMID- 24441899
TI  - Volume contentsVolume 8 (1997).

PMID- 24441900
TI  - From the editor.

PMID- 24441901
TI  - Work-related treatment for youth.

PMID- 24441902
TI  - School-based supported work/supported employment.

PMID- 24441903
TI  - Preparing Adolescents to Enter the Work ForceThe Effects of the Americans with
      Disabilities Act.

PMID- 24441904
TI  - Computers in Cognitive Rehabilitation and Academic ReintegrationRedefining the
      Role After Brain Injury.

PMID- 24441905
TI  - PMAC-ESPA Tool for Identifying Vocational Readiness Needs of Handicapped Children
      and Adolescents.

PMID- 24441906
TI  - The Adult with Learning DisabilitiesWhere Do All the Children Go?

PMID- 24441907
TI  - Body Mechanics for ChildrenWhen Should Prevention Start?

PMID- 24441908
TI  - Body BasicsA Cognitive Approach to Body Mechanics Training in Elementary School
      Back Pain Prevention Programs.

PMID- 24441909
TI  - Adolescent learning in two work environments.

PMID- 24441910
TI  - What happens when they finish school?

PMID- 24441911
TI  - Skills assessment module.

PMID- 24441913
TI  - 5-aza-2'-Deoxycytidine, a DNA methyltransferase inhibitor, facilitates the
      inorganic phosphorus-induced mineralization of vascular smooth muscle cells.
AB  - AIM: Vascular calcification, an independent risk factor for cardiovascular
      disease in patients with chronic kidney disease(CKD), refers to the
      mineralization of vascular smooth muscle cells(VSMCs) caused by phenotypic
      changes toward osteoblast-like cells. DNA methylation, mediated by DNA
      methyltransferases(DNMTs), plays an important role in the differentiation of
      osteoblasts. We herein assessed the effects of a DNMT inhibitor on phenotypic
      changes in VSMCs and the development of vascular calcification. METHODS: The
      effects of 5-aza-2'-deoxycytidine(5-aza-dC), a DNMT inhibitor, on human aortic
      smooth muscle cells(HASMCs) were evaluated. The expression and DNA methylation
      status of osteogenic genes were determined using RT-qPCR and bisulfite
      sequencing, respectively. Mineralization of HASMCs was induced by high
      concentrations of inorganic phosphate(Pi), as confirmed by quantitation of the
      calcium levels and von Kossa staining. Moreover, we examined the effects of the
      suppression of DNMT1 and/or alkaline phosphatase(ALP) on the mineralization of
      HASMCs. RESULTS: 5-aza-dC increased the expression and activity of ALP and
      reduced the DNA methylation levels of the ALP promoter region in the HASMCs. In
      addition, both treatment with 5-aza-dC and downregulation of the DNMT1 expression
      promoted the Pi-induced mineralization of HASMCs. Moreover, both treatment with
      phosphonoformic acid(PFA), a sodium-dependent phosphate transporter inhibitor,
      and suppression of the ALP expression inhibited the 5-aza-dC-promoted
      mineralization of HASMCs. CONCLUSIONS: The present study showed that DNMT
      inhibitors facilitate the Pi-induced development of vascular calcification via
      the upregulation of the ALP expression along with a reduction in the DNA
      methylation level of the ALP promoter region.

PMID- 24441914
TI  - Facile synthesis of nickel network supported three-dimensional graphene gel as a
      lightweight and binder-free electrode for high rate performance supercapacitor
      application.
AB  - Here we report a simple strategy to prepare three-dimensional graphene gel coated
      on nickel foam for supercapacitor applications by a simple 'dipping and drying'
      process. The supercapacitors based on three-dimensional graphene gel (G-gel@NF-1)
      exhibited high rate capability of 152 F g(-1) at 0.36 A g(-1) and 107 F g(-1) at
      90.9 A g(-1), good cycle stability with capacitance retention of 89% after 2000
      cycles and low internal resistance (0.58 Omega). Furthermore, a flexible
      electrode (G-gel@NF-2) was obtained by etching most of the nickel foam but
      maintains the conductive backbone of the nickel foam, which greatly reduces the
      total mass of the electrode (can be reduced from 30 mg cm(-2) to less than 5 mg
      cm(-2)), and can be compressed from a thickness of 1 mm to ~30 MUm. With the aid
      of a conductive network composed of a small amount of nickel, G-gel@NF-2 still
      has good performance in high rate capability and displays excellent flexible
      properties. The specific capacitance when the mass density of the electrode was
      only 5.4 mg cm(-2) still reached ~115 F g(-1). This strategy can improve the rate
      capability performance, greatly reduce the mass of the electrode, and lower the
      fabrication cost of supercapacitors. 

PMID- 24441915
TI  - Lenalidomide in combination with vorinostat and dexamethasone for the treatment
      of relapsed/refractory peripheral T cell lymphoma (PTCL): report of a phase I/II
      trial.
AB  - Given the poor outcome of relapsed and refractory peripheral T cell lymphoma
      (PTCL), we explored a combination of lenalidomide, vorinostat, and dexamethasone
      to test the feasibility of this therapy in relapsed and refractory PTCL. Eight
      patients were accrued: two peripheral T cell lymphoma, unspecified; five
      angioimmunoblastic T cell lymphoma; and one ALK-negative anaplastic large-cell
      lymphoma. A dose escalation of lenalidomide (days 1-21, q28) was planned using a
      3 + 3 design. As two patients treated with 10 mg/day experienced dose-limiting
      toxicity (thrombocytopenia grade 3, stroke grade 4), the primary end point of our
      trial was reached; the maximal tolerable dose of lenalidomide was 5 mg/day (level
      -I). Adverse events grade >=3 were observed as thrombocytopenia (23 %),
      leukocytopenia (15 %), anemia (8 %), and neutropenia (8 %). One complete
      remission (10.3 months), one partial remission (11.3 months), one stable disease
      (11.9 months), and four progressive disease (overall response rate 25 %) were
      observed. The median progression-free survival was 2.2 months and the median OS
      was 6.7 months. In conclusion, the poor results obtained with lenalidomide in
      combination with vorinostat and dexamethasone provide no arguments that could
      justify further investigation of this drug combination for the treatment of
      relapsed PTCL.

PMID- 24441916
TI  - Recombinant human interleukin-10 in patients with chronic myelomonocytic
      leukemia.

PMID- 24441917
TI  - Absolute lymphocyte count and risk of short-term infection in patients with
      immune thrombocytopenia.
AB  - Patients with immune thrombocytopenia (ITP) may be at increased risk of infection
      because of the steroids and other immunosuppressive agents used in its treatment.
      This study aimed to identify events that are associated with infection within 6
      months of diagnosis and the impact that infection has on survival. We
      retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years)
      diagnosed between January 1997 and August 2011. Every patient received steroid
      treatment according to the platelet count and the extent of bleeding. Logistic
      regression analysis was used to identify risk factors associated with the
      development of infection within 6 months of ITP being diagnosed. Sixty-two
      patients (25.9 %) developed an infection within 6 months of diagnosis.
      Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at
      diagnosis (<1 * 10(9)/l) was an independent risk factor for infection (P = 0.039;
      95 % confidence interval, 1.033-3.599; odds ratio, 1.928). The time to infection
      event is significant shorter in those of low ALC, compared with those of higher
      ALC (P = 0.032). Furthermore, the 1-year mortality rate after ITP diagnosis was
      significantly higher in those patients who developed an infection (P = 0.001).
      ITP patients with a low absolute lymphocyte count at diagnosis have an increased
      risk of infection, and those who develop infections have lower 1-year survival. 

PMID- 24441919
TI  - From the editor.

PMID- 24441918
TI  - Evaluation of effective dose conversion coefficients for Korean adults during
      medical x-ray examinations up to 150 keV through comparison with ICRP Publication
      74 and ICRP Publication 116.
AB  - A Monte Carlo program for calculating organ doses for patients undergoing medical
      x-ray examination (PCXMC) was used to calculate effective dose conversion
      coefficients for Korean adults. Two sets of effective dose results were
      calculated based on tissue weighting factors recommended in International
      Commission on Radiological Protection (ICRP) Publications 60 and 103 for
      monochromatic energy photons of 10, 15, 20, 30, 40, 50, 60, 70, 80, 100 and 150
      keV. The results were obtained for monoenergetic photons, since effective dose
      conversion coefficients recommended in ICRP Publications 74 and 116 were given
      for monochromatic energies, thereby enabling the comparison of our result to
      those suggested by the ICRP publications. The areas of comparison include: to
      observe effects due to changes in tissue weighting factors, modification within
      Medical Internal Radiation Dose (MIRD) phantoms and differences in phantom types.
      The phantom employed in the PCXMC program is a modified version of the phantom
      used in ICRP Publication 74, with additional organs that were added in order to
      take into account the updated tissue weighting factors given in ICRP Publication
      103. Both use MIRD phantoms but our study modified the phantom size to the
      average physical condition of Korean adults, while ICRP Publication 74 uses the
      phantom size of the reference man defined in ICRP Publication 23. On the other
      hand, the effective dose suggested in ICRP 116 was calculated using an entirely
      different type of phantom: a voxel phantom with the size of reference man.
      Although significant differences were observed for certain organ doses in the
      lateral beam directions, differences in the effective doses were within 5% for
      the anterior-posterior (AP) and posterior-anterior (PA) directions, and within
      16% in lateral directions when tissue weighting factors were applied and the
      variations were adjusted for all three comparisons. The results show that
      calculation of effective doses for Korean adults using the PCXMC (Caucasian-based
      phantom) is acceptable for the AP and PA directions, but care should be taken for
      lateral directions. 

PMID- 24441920
TI  - A review of functional capacity evaluation practice.
AB  - OBJECTIVES: This study evaluated the implementation of recommendations from a
      prior review of functional capacity evaluation practice in a regionalised
      rehabilitation service. The evaluation considered the acceptance of the
      recommendations and the current level of consistency of approach in practice.
      STUDY DESIGN: The study was qualitative in nature, using a descriptive survey and
      a focus group. Participants were occupational therapists of a major
      rehabilitation provider in Queensland, Australia. Eighteen of 48 therapists (38%)
      responded to the questionnaire. Eight therapists participated in the focus group.
      RESULTS: The results indicated some acceptance of the recommendations for
      functional capacity evaluation in areas such as procedure, reporting, equipment
      and model of evaluation. Further research into the reliability and validity of
      functional capacity evaluation was indicated. DISCUSSION: The low response rate
      did not allow conclusive results. However, the findings provided some evidence of
      consistency in functional capacity evaluation practice. The results are discussed
      in relation to current issues in functional capacity evaluation practice.

PMID- 24441921
TI  - Effects of a standing table on work productivity and posture in an adult with
      developmental disabilities.
AB  - The standing table is an assistive device designed to encourage occupational
      performance of the upper extremities while helping the person compensate for
      limitations in standing posture. We conducted three single-subject studies of a
      standing table used by a 52-year-old man with spastic cerebral palsy and mental
      retardation. In the first study, positioning in the standing table resulted in no
      discernible difference in work output per hour in comparison to his customary
      seated posture. In the second study, positioning in the standing table resulted
      in an unexpectedly small increase in work output in comparison to his customary
      method of standing without special support at the work bench. In the third study,
      we demonstrated that the standing table dramatically improved the erectness of
      his posture as measured by an infrared motion detector in comparison to his
      customary method of standing. Because work productivity depends on multiple
      factors, improved posture and biomechanical stability do no always result in a
      proportionate improvement in work output. There remain multiple justifications of
      equipment such as the standing table in work settings for adults with
      developmental disabilities. 

PMID- 24441922
TI  - Construct validity of a work environment impact scale.
AB  - This study examined the construct validity and the internal consistency of a
      newly developed assessment, the Work Environment Impact Scale (WEIS). After
      administration to 20 individuals with psychiatric disabilities, Rasch analysis
      was utilized to scrutinize the data. For this study, criteria for determining
      unexpected person/item responses were based on the following criteria: MNSQ > 1.3
      and <formula>$?underline{t}>2.0$</formula>. Persons/items with MNSQ < 0.7 and
      <formula>$?underline{t}<-2.0$</formula> were examined to enhance instrument
      precision but were not considered misfit. Results suggest that the WEIS is an
      appropriate and valid instrument to utilize with workers who have psychiatric
      disabilities. Overall, the items appeared to match the worker's need for
      performance, satisfaction, and well-being as the mean of persons measure is 0.30
      +/- 0.49 logits more than the mean of items measured. In addition the
      hierarchical order of items is consistent with literature identifying
      environmental press and affordance for workers with psychiatric disabilities.
      WEIS items constitute a uni-dimensional construct given that the summary
      statistics for both item and person had a MNSQ of 1.00 and 1.02 respectively and
      both <formula>$?underline{t}$</formula> values were -0.2. However, three items
      exceeded the established criterion for being too informative given the MNSQ < 0.7
      and a <formula>$?underline{t}<-2.0$</formula>., suggesting these needed to be
      revised to enhance the quality measurement of the instrument. One hundred percent
      of the workers fit the expected response pattern of the Rasch model suggesting
      that workers with greater satisfaction, performance and health had a higher
      degree of match with his/her occupational environment. In summary, anecdotal data
      suggested that the WEIS provided clinically relevant information useful for
      planning of work-related interventions or reasonable accommodations. 

PMID- 24441923
TI  - Sellers, shakers, peddlers, and hawkers: rehabilitation of sales workers.
AB  - Sales workers persuade, influence, inform and cajole customers, resulting in the
      purchase of a product or service. The selling profession is broken down into
      three categories: sales technology, general sales, and vending. Each of the
      categories are broken down and examined according to work tasks performed,
      preparation needed, and advancement opportunities. A case example of an injured
      agricultural chemical sales worker is provided to demonstrate an industry
      specific injury and development of an appropriate vocational rehabilitation plan.

PMID- 24441924
TI  - Factors that may influence the postural health of schoolchildren (K-12).
AB  - Ergonomic seating and proper positioning during the performance of activities is
      a major focus in the adult workplace. This focus, however, is typically ignored
      in classrooms where our youngest workers spend the majority of their time. A
      review of the literature was done to determine the effects of school furniture
      design on the postural health of schoolchildren (K-12). The review indicated that
      the adjustability of school furniture is an important design feature if children
      are to have equal educational opportunity, increased comfort, and decreased
      incidences of musculoskeletal symptoms. The effectiveness of ergonomic school
      furniture on schoolchildren has been demonstrated in only one study reviewed in
      this paper. The other studies are reviewed in an effort to identify: (1) the
      variation of anthropometric measures of children; (2) the performance of
      activities exposing children to various postures; and (3) the physical design
      features of school furniture as three factors which influence the postural health
      of schoolchildren. 

PMID- 24441925
TI  - Career adjustment via reasonable accommodations: the effects of an employee
      empowerment intervention for people with disabilities.
AB  - The article describes an experimental approach to increasing consumer
      participation in the Americans with Disabilities Act's Title I accommodation
      request process. Specifically, participants (N = 36) completed a structured
      interview to identify their needs for on-the-job accommodations, received
      detailed information about Title I provisions, and completed a social competence
      training program to assist them in requesting accommodations from their
      employers. Results indicated that the intervention was effective in increasing
      knowledge of Title I provisions and behavioral activity related to requesting and
      implementing accommodations. 

PMID- 24441926
TI  - Cultural considerations in the development of children with disabilities:
      implications for future work potential.
AB  - This article discusses the role of culture in the development of individuals with
      disabilities and how culture might affect one's self-esteem. Implications for
      future work potential are presented relative to self-esteem. The World Health
      Organization definitions of impairment, disability and handicap are presented as
      a reminder that someone with a disability is considered 'handicapped' by the
      society or culture in which one lives and works. Thus it is culture which helps
      to mold how one thinks about oneself and about what one is capable of doing in
      one's life. Next, culture is defined and parents' cultural beliefs about
      disability are examined. Cross-cultural studies are presented to illustrate
      differences between cultures relative to disabilities with implications for
      participation in an adult society. Cooperation and competition are mentioned.
      Several educational experiences are described in the context of culture. All who
      work with children with disabilities are urged to be aware of the culture(s) of
      each child and of the potential effects on self-esteem and on one's ability to be
      a contributing member of society. 

PMID- 24441927
TI  - Vocational and psychosocial adjustment for the client with a hand burn.
AB  - The disruptive effects of a hand burn injury permeate all aspects of a person's
      life. Hand burn rehabilitation is a multi-staged process; returning the client to
      functional occupational roles is its' ultimate goal. The purpose of this paper is
      to review the literature that examines return to work and psychosocial adjustment
      for the client with a hand burn. Other issues reviewed include: wound management;
      edema; positioning; activities of daily living; and therapeutic exercise. This
      paper concludes with an example of a work hardening clinic, and a case study, in
      order to illustrate the application of information provided. 

PMID- 24441928
TI  - Women and domestic violence: global dimensions, health consequences and
      intervention strategies.
AB  - Domestic violence against women is a significant health and social problem
      affecting virtually all societies. The sensitivities and stigma associated with
      domestic violence, the conceptualization of it primarily as a judicial and legal
      issue, and the lack of data on the dimensions of abuse have hampered
      understanding and the development of appropriate interventions. Secrecy,
      insufficient evidence, and social and legal barriers continue to make it
      difficult to acquire data on domestic violence against women. This paper
      describes the magnitude and health consequences of domestic violence. It explores
      factors that perpetuate violence against women, and discusses intervention
      strategies from around the world. 

PMID- 24441930
TI  - Mucin levels in saliva of adolescents with dental caries.
AB  - BACKGROUND: Human saliva, a complex secretion that contains a mixture of
      inorganic and organic molecules, plays an essential role in the maintenance of
      oral health. Mucins are the major macromolecular component of the secretion and
      are considered the first line of defense for epithelial tissues. The aim of this
      study was to compare levels of mucins (MUC5B, MUC7, and MUC1) in saliva of young
      subjects with dental caries. MATERIAL AND METHODS: All patients had DMF
      (decay/missing/filled) higher than value 0. Eight subjects with DMF=3 (control
      group) and 27 adolescents with DMF >11 (research group) were recruited for this
      study. Clinical evaluation procedures were oral examination, including tooth,
      periodontal, oral mucosal status, and collection of saliva samples. Saliva was
      collected for mucin assay. Enzyme-linked immunosorbent assay was used to
      quantitate MUC5B, MUC7, and MUC1. RESULTS: Our results indicate that adolescents
      with very high intensity of dental caries disease had increased levels of MUC1
      and MUC5B. The membrane mucin MUC1 protein levels in the group with DMF>11
      (research group) were higher compared to the group with DMF=3 (control group),
      and the increase was statistically significant (p=0.011). Similarly, secreted
      mucin MUC5B protein levels were higher (p=0.06) in the group with DMF>11
      (research group). Although MUC7 protein levels were slightly reduced in
      symptomatic subjects, the decrease was statistically insignificant (p=0.918).
      CONCLUSIONS: Our data suggest links between the production of mucins, especially
      MUC1 and MUC5B in saliva, and dental caries disease.

PMID- 24441931
TI  - The association between endothelial dysfunction and hypertensive retinopathy in
      essential hypertension.
AB  - BACKGROUND: Endothelial dysfunction, which is characterized by an imbalance
      between relaxing and contracting factors, procoagulant and anticoagulant
      substances, and between pro-inflammatory mediators, may play a particularly
      significant role in the pathogenesis of atherosclerosis. Numerous experimental
      and clinical reports suggest that a high von Willebrand factor (vWF) level
      reflects endothelial damage or dysfunction. Hypertensive retinopathy (HR) is a
      condition characterized by a spectrum of retinal vascular signs in people with
      elevated blood pressure. The pathophysiological mechanism of HR is not completely
      understood. Elevated blood pressure alone does not fully account for the extent
      of retinopathy. Endothelial dysfunction and mechanisms known to be involved in
      vascular lesions may be involved in the pathophysiological mechanism of HR.
      Therefore, this study was designed to answer the following questions: (i) Do vWf
      levels change in HR? and (ii) Is there any relation between degree of HR and vWf
      levels? MATERIAL AND METHODS: This study included 80 hypertensive patients with
      HR. Group 1 comprised 40 patients with grade I HR, and group 2 comprised 40
      patients with grade II HR. We selected 40 healthy subjects for the control group.
      RESULTS: Level of vWf in group 2 was significantly higher than in group 1
      (p=0.017) and the control group (p<0.001), and it was also higher in group 1 than
      in the control group (p<0.005). Also, vWf showed positive correlation with degree
      of HR in the hypertensive group (r=0.284, p=0.009). CONCLUSIONS: Our study
      suggests that endothelial dysfunction, which is a mechanism known to be involved
      in vascular lesions, may promote the development of HR.

PMID- 24441933
TI  - Synthesis, structural characterization, and multichannel anion and cation sensing
      studies of a bifunctional Ru(II) polypyridyl-imidazole based receptor.
AB  - A mixed-ligand monometallic ruthenium(ii) complex of composition [(bipy)2Ru(tpy
      Hbzim-dipy)](ClO4)2 (), where tpy-Hbzim-dipy = 4'-[4-(4,5-di-pyridin-2-yl-1H
      imidazol-2-yl)-phenyl]-[2,2';6',2'']terpyridine and bipy = 2,2'-bipyridine has
      been synthesized and characterized using standard analytical and spectroscopic
      techniques including X-ray crystallography. The complex displays very intense,
      ligand centered absorption bands in the UV and moderately intense MLCT bands in
      the visible region. On excitation at the MLCT bands, the complex exhibits strong
      luminescence at room temperature with lifetimes in the range of 116-257 ns,
      depending upon the nature of the solvents. The complex is found to undergo one
      reversible oxidation in the positive potential window (0 to +1.8 V) and two
      successive quasi-reversible reductions in the negative potential window (0 to 
      2.0 V). Both anion and cation binding properties of the receptor were thoroughly
      investigated in acetonitrile solution using (1)H NMR, absorption, steady state
      and time-resolved emission spectral studies and by cyclic voltammetry. The anion
      sensing studies revealed that the receptor acts as a "turn on" luminescence
      sensor for H2PO4(-) and HSO4(-) ions, and as a "turn off" sensor for F(-) and
      AcO(-) ions. It is evident that in the presence of excess F(-) and AcO(-) ions,
      deprotonation of the imidazole N-H fragment of the receptor occurs, an event
      which is signaled by the change of color from orange yellow to red visible to the
      naked eye. On the other hand, the probable mode of interaction of the receptors
      with H2PO4(-) and HSO4(-) ions is through hydrogen bonding interaction. The
      cation-sensing properties showed that the receptor was found to exhibit a
      colorimetric sensing ability that was highly selective for Fe(2+), as evidenced
      by the distinct color change from yellow orange to deep red-violet to the naked
      eye over the other cations studied (Mn(2+), Fe(3+), Co(2+), Ni(2+), Cu(2+),
      Zn(2+), Cd(2+), and Hg(2+)). 

PMID- 24441932
TI  - The neurologist's dilemma: a comprehensive clinical review of Bell's palsy, with
      emphasis on current management trends.
AB  - BACKGROUND: Recent advances in Bell's palsy (BP) were reviewed to assess the
      current trends in its management and prognosis. MATERIAL/METHODS: We retrieved
      the literature on BP using the Cochrane Database of Systematic Reviews, PubMed,
      and Google Scholar. Key words and phrases used during the search included 'Bell's
      palsy', 'Bell's phenomenon', 'facial palsy', and 'idiopathic facial paralysis'.
      Emphasis was placed on articles and randomized controlled trails (RCTs) published
      within the last 5 years. RESULTS: BP is currently considered the leading disorder
      affecting the facial nerve. The literature is replete with theories of its
      etiology, but the reactivation of herpes simplex virus isoform 1 (HSV-1) and/or
      herpes zoster virus (HZV) from the geniculate ganglia is now the most strongly
      suspected cause. Despite the advancements in neuroimaging techniques, the
      diagnosis of BP remains one of exclusion. In addition, most patients with BP
      recover spontaneously within 3 weeks. CONCLUSIONS: Corticosteroids are currently
      the drug of choice when medical therapy is needed. Antivirals, in contrast, are
      not superior to placebo according to most reliable studies. At the time of
      publication, there is no consensus as to the benefit of acupuncture or surgical
      decompression of the facial nerve. Long-term therapeutic agents and adjuvant
      medications for BP are necessary due to recurrence and intractable cases. In the
      future, large RCTs will be required to determine whether BP is associated with an
      increased risk of stroke.

PMID- 24441934
TI  - Targeted protein quantification using sparse reference labeling.
AB  - Targeted proteomics is a method of choice for accurate and high-throughput
      quantification of predefined sets of proteins. Many workflows use isotope-labeled
      reference peptides for every target protein, which is time consuming and costly.
      We report a statistical approach for quantifying full protein panels with a
      reduced set of reference peptides. This label-sparse approach achieves accurate
      quantification while reducing experimental cost and time. It is implemented in
      the software tool SparseQuant. 

PMID- 24441935
TI  - Continuous throughput and long-term observation of single-molecule FRET without
      immobilization.
AB  - We present an automated microfluidic platform that performs multisecond
      observation of single molecules with millisecond time resolution while bypassing
      the need for immobilization procedures. With this system, we confine biomolecules
      to a thin excitation field by reversibly collapsing microchannels to
      nanochannels. We demonstrate the power of our method by studying a variety of
      complex nucleic acid and protein systems, including DNA Holliday junctions,
      nucleosomes and human transglutaminase 2. 

PMID- 24441936
TI  - Objective comparison of particle tracking methods.
AB  - Particle tracking is of key importance for quantitative analysis of intracellular
      dynamic processes from time-lapse microscopy image data. Because manually
      detecting and following large numbers of individual particles is not feasible,
      automated computational methods have been developed for these tasks by many
      groups. Aiming to perform an objective comparison of methods, we gathered the
      community and organized an open competition in which participating teams applied
      their own methods independently to a commonly defined data set including diverse
      scenarios. Performance was assessed using commonly defined measures. Although no
      single method performed best across all scenarios, the results revealed clear
      differences between the various approaches, leading to notable practical
      conclusions for users and developers. 

PMID- 24441938
TI  - Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the
      initiation and progress of atherosclerosis in a rat model.
AB  - Acute coronary syndrome is a serious medical emergency. It occurs when an
      atherosclerotic plaque ruptures, leading to thrombus formation within a coronary
      artery. Previous studies have shown that T cells are involved in the initiation
      and progression of acute coronary syndrome. CD4(+)CD28(null) T lymphocytes
      increase in atherosclerotic plaque, and voltage-gated potassium channel Kv1.3
      blockers can suppress the function of these cells in vitro by preventing
      exocytosis of their cytoplasmic granules. The purpose of this study was to
      investigate the effect of PAP-1, a small molecule voltage-gated potassium channel
      Kv1.3 blocker, on the development of atherosclerosis (AS) in a rat model and the
      potential mechanism for this effect. Plasma lipids, interferongamma, CRP,
      CD4(+)CD28(null) T cells, and perforin were increased and unstable
      atherosclerotic plaques developed in the rat model of AS. Blockade of the Kv1.3
      potassium channel via PAP-1 administration decreased perforin levels and
      prevented plaque formation but had no effect on the other changes seen in this AS
      model. These findings suggest that the small molecule, voltage-gated potassium
      channel Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model,
      most likely by inhibiting the exocytosis of cytoplasmic granules from
      CD4(+)CD28(null) T cells. 

PMID- 24441937
TI  - Tamoxifen use for the management of mania: a review of current preclinical
      evidence.
AB  - RATIONALE: Preliminary data on the efficacy of tamoxifen in reducing manic
      symptoms of bipolar disorder (BD) suggest that this agent may be a potential
      treatment for the management of this psychiatric disorder. However, the antimanic
      properties of tamoxifen have not been fully elucidated, hampering the development
      and/or use of mood-stabilising drugs that may share its same therapeutic
      mechanisms of action. Notably, we may gain a greater understanding of the
      neurobiological and therapeutic properties of tamoxifen by using suitable animal
      models of mania. OBJECTIVES: Here, we review the preclinical studies that have
      evaluated the effects of tamoxifen to provide an overview of the current progress
      in our understanding of its antimanic actions, highlighting the critical role of
      protein kinase C (PKC) as a therapeutic target for the treatment of BD.
      CONCLUSIONS: To date, this field has struggled to make significant progress, and
      the organisation of an explicit battery of tests is a valuable tool for assessing
      a number of prominent facets of BD, which may provide a greater understanding of
      the entire scope of this disease.

PMID- 24441940
TI  - Pharmacoinformatic approaches to understand complexation of dendrimeric
      nanoparticles with drugs.
AB  - Nanoparticle based drug delivery systems are gaining popularity due to their wide
      spectrum advantages over traditional drug delivery systems; among them,
      dendrimeric nano-vectors are the most widely explored carriers for pharmaceutical
      and biomedical applications. The precise mechanism of encapsulation of drug
      molecules inside the dendritic matrix, delivery of drugs into specific cells,
      interactions of nano-formulation with biological targets and proteins, etc.
      present a substantial challenge to the scientific understanding of the subject.
      Computational methods complement experimental techniques in the design and
      optimization of drug delivery systems, thus minimizing the investment in drug
      design and development. Significant progress in computer simulations could
      facilitate an understanding of the precise mechanism of encapsulation of
      bioactive molecules and their delivery. This review summarizes the
      pharmacoinformatic studies spanning from quantum chemical calculations to coarse
      grained simulations, aimed at providing better insight into dendrimer-drug
      interactions and the physicochemical parameters influencing the binding and
      release mechanism of drugs. 

PMID- 24441939
TI  - Reduced erythrocyte deformability associated with hypoargininemia during
      Plasmodium falciparum malaria.
AB  - The mechanisms underlying reduced red blood cell (RBC) deformability during
      Plasmodium falciparum (Pf) malaria remain poorly understood. Here, we explore the
      possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC
      deformability in Pf-infected patients and parasite cultures. RBC deformability
      was reduced during the acute attack (day0) and returned to normal values upon
      convalescence (day28). Day0 values correlated with plasma L-arginine levels (r =
      0.69; p = 0.01) and weakly with parasitemia (r = -0.38; p = 0.006). In vitro,
      day0 patient's plasma incubated with ring-stage cultures at 41 degrees C reduced
      RBC deformability, and this effect correlated strongly with plasma L-arginine
      levels (r = 0.89; p < 0.0001). Moreover, addition of exogenous L-arginine to the
      cultures increased deformability of both Pf-free and trophozoite-harboring RBCs.
      NO synthase activity, evidenced in Pf-infected RBCs, induced L-arginine-dependent
      NO production. These data show that hypoargininemia during P. falciparum malaria
      may altogether impair NO production and reduce RBC deformability, particularly at
      febrile temperature. 

PMID- 24441942
TI  - Systematic study of high-frequency ultrasonic transducer design for laser
      scanning photoacoustic ophthalmoscopy.
AB  - Photoacoustic ophthalmoscopy (PAOM) is a high-resolution in vivo imaging modality
      that is capable of providing specific optical absorption information for the
      retina. A high-frequency ultrasonic transducer is one of the key components in
      PAOM, which is in contact with the eyelid through coupling gel during imaging.
      The ultrasonic transducer plays a crucial role in determining the image quality
      affected by parameters such as spatial resolution, signal-to-noise ratio, and
      field of view. In this paper, we present the results of a systematic study on a
      high-frequency ultrasonic transducer design for PAOM. The design includes
      piezoelectric material selection, frequency selection, and the fabrication
      process. Transducers of various designs were successfully applied for capturing
      images of biological samples in vivo. The performances of these designs are
      compared and evaluated.

PMID- 24441941
TI  - Medical hyperspectral imaging: a review.
AB  - Hyperspectral imaging (HSI) is an emerging imaging modality for medical
      applications, especially in disease diagnosis and image-guided surgery. HSI
      acquires a three-dimensional dataset called hypercube, with two spatial
      dimensions and one spectral dimension. Spatially resolved spectral imaging
      obtained by HSI provides diagnostic information about the tissue physiology,
      morphology, and composition. This review paper presents an overview of the
      literature on medical hyperspectral imaging technology and its applications. The
      aim of the survey is threefold: an introduction for those new to the field, an
      overview for those working in the field, and a reference for those searching for
      literature on a specific application.

PMID- 24441944
TI  - Noninvasive respiration movement sensor based on distributed Bragg reflector
      fiber laser with beat frequency interrogation.
AB  - A distributed Bragg reflector fiber laser-based respiration movement monitoring
      system has been proposed and experimentally demonstrated. To fabricate the
      sensing element for respiration monitoring, a fixture that consists of a plastic
      plate, a section of elastic textile is employed to experience and transfer the
      belly expansion induced pressure onto the cross-section of the laser cavity. By
      tracing the change of the beat signal that generates between two polarization
      lasing modes, the information of the respiration movement can be extracted in
      real time. Experimental studies have demonstrated that the system is able to
      detect both respiration waveform and rate simultaneously. Moreover, the recorded
      results show that the different gestures as well as the physiology conditions can
      be distinguished by monitoring the amplitude and period change of the waveform.
      It is anticipated that the proposed fiber laser-based sensor would be highly
      suitable for respiratory monitoring.

PMID- 24441943
TI  - Network signatures of nuclear and cytoplasmic density alterations in a model of
      pre and postmetastatic colorectal cancer.
AB  - Cells contributing to the pathogenesis of cancer possess cytoplasmic and nuclear
      structural alterations that accompany their aberrant genetic, epigenetic, and
      molecular perturbations. Although it is known that architectural changes in
      primary and metastatic tumor cells can be quantified through variations in
      cellular density at the nanometer and micrometer spatial scales, the
      interdependent relationships among nuclear and cytoplasmic density as a function
      of tumorigenic potential has not been thoroughly investigated. We present a
      combined optical approach utilizing quantitative phase microscopy and partial
      wave spectroscopic microscopy to perform parallel structural characterizations of
      cellular architecture. Using the isogenic SW480 and SW620 cell lines as a model
      of pre and postmetastatic transition in colorectal cancer, we demonstrate that
      nuclear and cytoplasmic nanoscale disorder, micron-scale dry mass content, mean
      dry mass density, and shape metrics of the dry mass density histogram are
      uniquely correlated within and across different cellular compartments for a given
      cell type. The correlations of these physical parameters can be interpreted as
      networks whose nodal importance and level of connection independence differ
      according to disease stage. This work demonstrates how optically derived
      biophysical parameters are linked within and across different cellular
      compartments during the architectural orchestration of the metastatic phenotype.

PMID- 24441945
TI  - Detachable microsphere scalpel tips for potential use in ophthalmic surgery with
      the erbium:YAG laser.
AB  - Vitreoretinal surgery is performed using mechanical dissection that sometimes
      results in iatrogenic complications, including vitreous hemorrhage, retinal
      breaks, incomplete membrane delamination, retinal distortion, microscopic damage,
      etc. An ultraprecise laser probe would be an ideal tool for cutting away
      pathologic membranes; however, the depth of surgery should be precisely
      controlled to protect the sensitive underlying retina. The ultraprecise surgical
      microprobe formed by chains of dielectric spheres for use with the erbium:YAG
      laser source (lambda=2940  nm), with extremely short optical penetration depth in
      tissue, was optimized. Numerical modeling demonstrated a potential advantage of
      five-sphere focusing chains of sapphire spheres with index n=1.71 for ablating
      the tissue with self-limited depth around 10 to 20 MUm. Novel detachable
      microsphere scalpel tips formed by chains of 300 MUm sapphire (or ruby) spheres
      were tested on ophthalmic tissues, ex vivo. Detachable scalpel tips could allow
      for reusability of expensive mid-infrared trunk fibers between procedures, and
      offer more surgical customization by interchanging various scalpel tip
      configurations. An innovative method for aiming beam integration into the
      microsphere scalpel to improve the illumination of the surgical site was also
      shown. Single Er:YAG pulses of 0.2 mJ and 75-MUs duration produced ablation
      craters in cornea epithelium for one, three, and five sphere structures with the
      latter generating the smallest crater depth (10 MUm) with the least amount of
      thermal damage depth (30 MUm). Detachable microsphere laser scalpel tips may
      allow surgeons better precision and safety compared to mechanical scalpels when
      operating on delicate or sensitive areas like the retina.

PMID- 24441946
TI  - Refractory lactic acidosis in CD30 positive gastric cancer.

PMID- 24441947
TI  - Normal karyotype acute myeloid leukemia with the CD7+ CD15+ CD34+ HLA-DR +
      immunophenotype is a clinically distinct entity with a favorable outcome.
AB  - Recently, the presence of CEBPA mutation was identified as an important
      prognostic factor for normal karyotype (NK) acute myeloid leukemia (AML). Because
      AML with CEBPA mutation is closely associated with CD7, CD15, CD34, and HLA-DR
      expression, we investigated the prognostic implications of CD7+ CD15+ CD34+ HLA
      DR + immunophenotype in NK-AML. We analyzed the immunophenotype of 329 patients
      with NK-AML from the Japan Adult Leukemia Study Group (JALSG) AML97 population.
      NK-AML with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype was classified as the
      CEBPA type, and NK-AML that did not meet this criterion was considered as the non
      CEBPA type. The influence of the CEBPA status on event-free survival (EFS) and
      overall survival (OS) was assessed using log-rank test and a multivariate Cox
      proportional hazard regression model. Furthermore, the surface antigen expression
      profile in AML according to the CEBPA mutation status (monoallelic or biallelic)
      was also investigated. Of the 329 NK-AML patients that were studied, 39 and 243
      were classified as having CEBPA and non-CEBPA type NK-AML, respectively. Patients
      with CEBPA type NK-AML had significantly better EFS and OS than those with non
      CEBPA type NK-AML. Multivariate analysis showed that the CEBPA type and white
      blood cell (WBC) counts of >20 * 10(9)/L were independent prognostic factors for
      EFS and OS. Moreover, NK-AML with the biallelic CEBPA mutation was more closely
      associated with CD34 positivity than that with the monoallelic CEBPA mutation. NK
      AML with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype is a clinically discrete
      entity, and this may have a possible role in risk stratification. 

PMID- 24441948
TI  - Prognostic impact of beta-2 microglobulin in patients with extranodal natural
      killer/T cell lymphoma.
AB  - Although serum beta-2 microglobulin (B2M) has been suggested as an independent
      prognostic factor for several lymphoproliferative diseases, it has rarely been
      investigated in extranodal natural killer/T cell lymphoma (ENKTL). From a
      prospectively collected database, 145 patients with ENKTL were identified. Among
      them, a total of 101 patients were included in the analysis, with exclusion of
      patients without baseline serum B2M level and those did not receive anticancer
      therapy. Serum B2M (<3.0 vs. >=3.0 mg/L) was analyzed for association with
      overall survival (OS). Seventy-nine (78 %) patients had nasal ENKTL, and 22 (22
      %) had extranasal ENKTL. In overall patients, median OS was 26.7 months (95 %
      confidence interval (CI), not assessable), with a median follow-up of 32.4 months
      (range, 0.9-155.2 months). While median OS was not reached in patients with nasal
      ENKTL, extranasal ENKTL group had median OS of 5.1 months (95 % CI, 1.2-8.9
      months; p < 0.001). Baseline serum B2M was significantly associated with OS in
      patients with nasal ENKTL (p < 0.001). This was consistent in limited (stages I
      and II) nasal ENKTL (p = 0.002) and disseminated (stages III and IV) nasal ENKTL
      (p = 0.02). However, there was no difference of OS in extranasal ENKTL patients
      (p = 0.69). In multivariate analysis including other prognostic factors, elevated
      serum B2M was significantly associated with poor OS (hazard ratio (HR) = 3.8, 95
      % CI 1.7-8.2, p = 0.001, in a model including Korean Prognostic Index, and HR =
      3.6, 95 % CI 1.6-8.2, p = 0.002, in a model including International Prognostic
      Index). In patients with nasal ENKTL, baseline serum B2M is a powerful prognostic
      factor. The prognostic value of B2M was independent of previously established
      prognostic models. Further investigations are necessary to validate the role of
      B2M in ENKTL. 

PMID- 24441949
TI  - Genetic analysis of single-locus and epistatic QTLs for seed traits in an adapted
      * nuna RIL population of common bean (Phaseolus vulgaris L.).
AB  - KEY MESSAGE: The QTLs analyses here reported demonstrate the significant role of
      both individual additive and epistatic effects in the genetic control of seed
      quality traits in the Andean common bean. Common bean shows considerable
      variability in seed size and coat color, which are important agronomic traits
      determining farmer and consumer acceptability. Therefore, strategies must be
      devised to improve the genetic base of cultivated germplasm with new alleles that
      would contribute positively to breeding programs. For that purpose, a population
      of 185 recombinant inbred lines derived from an Andean intra-gene pool cross,
      involving an adapted common bean (PMB0225 parent) and an exotic nuna bean
      (PHA1037 parent), was evaluated under six different--short and long-day-
      environmental conditions for seed dimension, weight, color, and brightness
      traits, as well as the number of seed per pod. A multi-environment Quantitative
      Trait Loci (QTL) analysis was carried out and 59 QTLs were mapped on all linkage
      groups, 18 of which had only individual additive effects, while 27 showed only
      epistatic effects and 14 had both individual additive and epistatic effects.
      Multivariate models that included significant QTL explained from 8 to 68 % and 2
      to 15 % of the additive and epistatic effects, respectively. Most of these QTLs
      were consistent over environment, though interactions between QTLs and
      environments were also detected. Despite this, QTLs with differential effect on
      long-day and short-day environments were not found. QTLs identified were
      positioned in cluster, suggesting that either pleiotropic QTLs control several
      traits or tightly linked QTLs for different traits map together in the same
      genomic regions. Overall, our results show that digenic epistatic interactions
      clearly play an important role in the genetic control of seed quality traits in
      the Andean common bean.

PMID- 24441950
TI  - Dielectrophoretic immobilisation of antibodies on microelectrode arrays.
AB  - A silicon based chip device with a regular array of more than 100,000 cylindrical
      sub-microelectrodes has been developed for the dielectrophoretic (DEP)
      manipulation of nanoparticles and molecules in solution. It was fabricated by a
      standard CMOS (complementary metal oxide semiconductor) compatible process. The
      distribution of the electrical field gradient was calculated to predict the
      applicability of the setup. Heating due to field application was determined
      microscopically using a temperature sensitive fluorescent dye. Depending on
      voltage and frequency, temperature increase was found to be compatible with
      protein function. Successful field controlled immobilisation of biomolecules from
      solution was demonstrated with the autofluorescent protein R-phycoerythrin (RPE)
      and with fluorescently labelled IgG antibodies. Biological activity after DEP
      application was proven by immobilisation of an anti-RPE antibody and subsequent
      binding of RPE. These results demonstrate that the developed chip system allows
      the directed immobilisation of proteins onto microelectrodes by dielectrophoresis
      without the need for any chemical modification and that protein function is
      preserved. Being based on standard lithographical methods, further
      miniaturisation and on-chip integration of electronics towards a multiparameter
      single cell analysis system appear near at hand.

PMID- 24441953
TI  - From the editor.

PMID- 24441951
TI  - Soluble lutein in combination with brilliant blue as a new dye for
      chromovitrectomy.
AB  - A new dye for vitreoretinal surgery comprised of soluble lutein/zeaxanthin 1 %
      and brilliant blue 0.025 % is advantageous compared with other dyes currently
      used for chromovitrectomy, and showed no signs of toxicity at 1 month of follow
      up. PURPOSE: To evaluate the feasibility and safety of a dye [soluble
      lutein/zeaxanthin (LZ) 1 % and brilliant blue (BB) 0.025 %] for improving removal
      of vitreous, epiretinal membranes (ERM), and internal limiting membranes (ILM) in
      humans. METHODS: We prospectively evaluated 18 eyes treated surgically for a
      macular hole or ERM. Eighteen surgeons performed chromovitrectomy using the dye,
      and completed a questionnaire to evaluate the efficacy and safety of the dye. .
      Examinations included best-corrected visual acuity and intraocular pressure
      measurements and optical coherence tomography, fluorescein angiography, and
      autofluorescence performed at baseline and days 1, 7, and 30 postoperatively.
      RESULTS: The green dye was deposited on the posterior pole; vigorous dye flushing
      into the vitreous cavity was unnecessary. All surgeons reported that the ILM
      stained greenish-blue; 94.4 % reported ILM peeling adequate; the ERM stained
      poorly. No evidence of toxicity was observed. CONCLUSION: The new dye deposited
      on the posterior pole due to its higher density. The ability to stain the ILM was
      similar to BB. The new dye has ability to stain the vitreous, hyaloid, and
      especially the ILM satisfactorily. The new dye may be useful during
      chromovitrectomy.

PMID- 24441954
TI  - Health care delivery across cultures.

PMID- 24441952
TI  - Bilateral implantation of multifocal versus monofocal intraocular lens in
      children above 5 years of age.
AB  - PURPOSE: To evaluate visual results and complications after bilateral
      implantation of multifocal versus monofocal intraocular lens (IOL) in children
      above five years of age. METHODS: In this prospective non-randomized controlled
      trial, children with bilateral developmental cataract above five years of age
      were divided into two groups - Group A implanted with multifocal IOL (both
      refractive and diffractive) and Group B implanted with monofocal IOL in both
      eyes. Outcome measures of best corrected visual acuity (BCVA) for distance,
      distance-corrected near visual acuity (DCNVA), mean refractive spherical
      equivalent (MRSE), contrast sensitivity, stereopsis and complications such as
      posterior capsular opacification (PCO) and glare were analyzed using the Mann
      Whitney U and the Wilcoxon Signed Rank tests. RESULTS: Forty-two eyes of 21
      children (mean age: 7.19 years, range: 5-12 years) were included in the study.
      Group A included 14 eyes (seven children) Group B included 28 eyes (14 children).
      Both groups showed significant improvement in BCVA at one year follow-up, but no
      significant difference was found on comparing contrast sensitivity. Stereopsis
      was slightly better in Group A (125.71 arc-sec) as compared to Group B (140 arc
      sec) (p = 0.280). Most patients in Group A were spectacle-independent for near
      (71.4 %) versus Group B. MRSE at one year was 0.21 in Group A and 0.5 in Group B.
      Incidence of PCO was similar in either groups (35.7 %). No intraoperative
      complication was noted in any child. CONCLUSION: Multifocal IOL implantation is a
      viable option in children above five years of age with bilateral cataract.

PMID- 24441955
TI  - WorkAn Occupational Perspective.

PMID- 24441956
TI  - We've Been Working On the RailwayDeveloping Hospital-Industry Partnerships.

PMID- 24441957
TI  - Worker role and work-related needs of mentally ill and healthy people.

PMID- 24441958
TI  - Factor Structure of an Aspects of Work ScaleA Brief Report.

PMID- 24441959
TI  - Occupational Therapy Work Training Programs For Brain-Damaged IndividualsA
      Swedish Program.

PMID- 24441960
TI  - Rehabilitation and Return to WorkDo Other Countries Succeed?

PMID- 24441961
TI  - Vocational rehabilitation and occupational therapy in Japan for people with
      psychiatric disorders.

PMID- 24441962
TI  - Back Pain Prevention Programs in SchoolsThe Role of the Physical Education
      Teacher.

PMID- 24441963
TI  - Cognitive Levels and Work RecommendationsA Study of Chronic Psychiatric Patients
      in the Community.

PMID- 24441964
TI  - Vocational rehabilitation and occupational therapy in Japan.

PMID- 24441965
TI  - Certification nightmare.

PMID- 24441966
TI  - WEST Tool Sort.

PMID- 24441967
TI  - Doctor-patient communication without family is most frequently practiced in
      patients with malignant tumors in home medical care settings.
AB  - Promotion of home medical care is absolutely necessary in Japan where is a
      rapidly aging society. In home medical care settings, triadic communications
      among the doctor, patient and the family are common. And "communications just
      between the doctor and the patient without the family" (doctor-patient
      communication without family, "DPC without family") is considered important for
      the patient to frankly communicate with the doctor without consideration for the
      family. However, the circumstances associated with DPC without family are
      unclear. Therefore, to identify the factors of the occurrence of DPC without
      family, we conducted a cross-sectional mail-in survey targeting 271 families of
      Japanese patients who had previously received home medical care. Among 227
      respondents (83.8%), we eventually analyzed data from 143, excluding families of
      patients with severe hearing or cognitive impairment and severe verbal
      communication dysfunction. DPC without family occurred in 26.6% (n = 38) of the
      families analyzed. A multivariable logistic regression analysis was performed
      using a model including Primary disease, Daily activity, Duration of home medical
      care, Interval between doctor visits, Duration of doctor's stay, Existence of
      another room, and Spouse as primary caregiver. As a result, DPC without family
      was significantly associated with malignant tumor as primary disease (OR, 3.165;
      95% CI, 1.180-8.486; P = 0.022). In conclusion, the visiting doctors should bear
      in mind that the background factor of the occurrence of DPC without family is
      patient's malignant tumors. 

PMID- 24441969
TI  - Guest Editors' note.

PMID- 24441970
TI  - Diabetes mellitus: medical aspects and rehabilitation implications.
AB  - This article examines the etiologies, incidence and prevalence of diabetes
      mellitus - a chronic, systemic disease of the endocrine system. It presents
      current information for rehabilitation professionals concerning diagnosis,
      treatment, and physiological effects of this, most common of all endocrine
      disorders. 

PMID- 24441971
TI  - Ecological assessment of the career maintenance needs of employees with diabetes.
AB  - The article presents four case studies of employees with diabetes. The authors
      examine participants' post-employment accommodation needs in four areas: worksite
      accessibility; performance of essential job functions; job mastery; and job
      satisfaction. Data were collected via the Work Experience Survey, an established
      career maintenance needs assessment tool. 

PMID- 24441968
TI  - Alterations to global but not local motion processing in long-term ecstasy (MDMA)
      users.
AB  - RATIONALE: Growing evidence indicates that the main psychoactive ingredient in
      the illegal drug "ecstasy" (methylendioxymethamphetamine) causes reduced activity
      in the serotonin and gamma-aminobutyric acid (GABA) systems in humans. On the
      basis of substantial serotonin input to the occipital lobe, recent research
      investigated visual processing in long-term users and found a larger magnitude of
      the tilt aftereffect, interpreted to reflect broadened orientation tuning
      bandwidths. Further research found higher orientation discrimination thresholds
      and reduced long-range interactions in the primary visual area of ecstasy users.
      OBJECTIVES: The aim of the present research was to investigate whether serotonin
      mediated V1 visual processing deficits in ecstasy users extend to motion
      processing mechanisms. METHOD: Forty-five participants (21 controls, 24 drug
      users) completed two psychophysical studies: A direction discrimination study
      directly measured local motion processing in V1, while a motion coherence task
      tested global motion processing in area V5/MT. RESULTS: "Primary" ecstasy users
      (n = 18), those without substantial polydrug use, had significantly lower global
      motion thresholds than controls [p = 0.027, Cohen's d = 0.78 (large)], indicating
      increased sensitivity to global motion stimuli, but no difference in local motion
      processing (p = 0.365). CONCLUSION: These results extend on previous research
      investigating the long-term effects of illicit drugs on visual processing. Two
      possible explanations are explored: defuse attentional processes may be
      facilitating spatial pooling of motion signals in users. Alternatively, it may be
      that a GABA-mediated disruption to V5/MT processing is reducing spatial
      suppression and therefore improving global motion perception in ecstasy users.

PMID- 24441972
TI  - Employment patterns among parents of children with insulin-dependent diabetes
      mellitus (IDDM).
AB  - OBJECTIVE: To examine the influence of diabetes on the employment patterns of
      parents of children living with diabetes. STUDY DESIGN: A case-control study of
      197 families with an IDDM child and 142 control families without IDDM children
      was conducted. Case families were identified from a population-based diabetes
      registry. Brothers and sisters of the parents in the IDDM families were asked to
      participate as controls. Employment rates, absenteeism related to child care, and
      changes in work status were assessed by means of a questionnaire. Surveys were
      obtained from 85% of the families (172 case; 118 control). RESULTS: No difference
      was found between the IDDM and control families in the overall rate of employment
      and changes in work patterns. However, IDDM families were more likely to report
      absences from work related to child care (58% vs. 45%, P < 0.05). This impact was
      greatest for the working mothers. The greatest impact of IDDM on employment may
      be faced by single parents, who reported lower rates of employment and higher
      rates of absenteeism and changes in work patterns. CONCLUSIONS: Families face
      decisions regarding employment and the appropriate level of care for children
      with diabetes. These data illustrate that most families with an IDDM child have
      employment experiences similar to those of families without diabetic children.
      Larger sample sizes of single parent families are necessary to confirm these
      findings.

PMID- 24441973
TI  - Twenty questions surrounding unpaid medical leave: Navigating the Bermuda
      Triangle of employment law.
AB  - No federal or state lawmaker could have foreseen the nuances involved in the
      mutual implementations of the Americans with Disabilities Act, the Family and
      Medical Leave Act, and state workers compensation statutes. These laws are
      compared and contrasted on a number of key issues. Readers are provided with a
      decision matrix to guide them and those they represent in the judicious
      invocation of the most beneficial statute for each issue. 

PMID- 24441974
TI  - Understanding the needs of diabetics in the workplace: a clinician's perspective.
AB  - The purpose of this article is to acquaint Occupational and Physical therapists
      with the diabetic client so as to better understand their disease and therefore
      aid in interventions necessary for their continued performance in the workplace.
      The article will include sections on self care techniques necessary for control
      of glucose levels, acute and chronic complications of the disease process,
      emotional stress, both internal and external, that diabetics face daily plus
      stress management ideas. Finally, the role of the professional in aiding
      diabetics through specific modifications in their work environment as mandated by
      the Americans with Disabilities Act will be addressed as it applies to this
      diverse population. It is written from the perspective of a diabetic who is
      trained as a psychologist, started an educational clinic for diabetics, and has
      written a book with the Joslin Diabetes Center, The Joslin Gourmet Diabetes
      Cookbook. 

PMID- 24441975
TI  - Enhancing the employment potential of people with diabetes mellitus: guidelines
      for research and practice.
AB  - This article offers recommendations to researchers, policymakers and
      rehabilitation professionals to improve the employment prospects for Americans
      with diabetes mellitus. An early intervention, interdisciplinary approach is
      emphasized - one that integrates career counseling and employment consultation
      into a 'total treatment' framework. 

PMID- 24441976
TI  - Chronic pain intervention: promoting return to function.
AB  - Although interdisciplinary treatment has been widely recognized as beneficial,
      very few studies have focused on the combination of factors that promote return
      to function for clients with chronic pain. This lack of synthesis results in
      factionalized and uncoordinated client care. This article, incorporating
      literature from a diversity of fields and an illustrative case study, is an
      attempt to make a case for 12 guidelines, which are a synthesis of the knowledge
      gained by those autonomous professional bodies. 

PMID- 24441977
TI  - World literacy: obstacles and opportunities.

PMID- 24441978
TI  - A model for work injury prevention.

PMID- 24441979
TI  - Rehabilitation ergonomics: a client-centered ecological approach.

PMID- 24441981
TI  - Encapsulate-and-peel: fabricating carbon nanotube CMOS integrated circuits in a
      flexible ultra-thin plastic film.
AB  - Fabrication of single-walled carbon nanotube thin film (SWNT-TF) based integrated
      circuits (ICs) on soft substrates has been challenging due to several processing
      related obstacles, such as printed/transferred SWNT-TF pattern and electrode
      alignment, electrical pad/channel material/dielectric layer flatness, adherence
      of the circuits onto the soft substrates etc. Here, we report a new approach that
      circumvents these challenges by encapsulating pre-formed SWNT-TF-ICs on hard
      substrates into polyimide (PI) and peeling them off to form flexible ICs on a
      large scale. The flexible SWNT-TF-ICs show promising performance comparable to
      those circuits formed on hard substrates. The flexible p- and n-type SWNT-TF
      transistors have an average mobility of around 60 cm(2) V(-1) s(-1), a
      subthreshold slope as low as 150 mV dec(-1), operating gate voltages less than 2
      V, on/off ratios larger than 10(4) and a switching speed of several kilohertz.
      The post-transfer technique described here is not only a simple and cost
      effective pathway to realize scalable flexible ICs, but also a feasible method to
      fabricate flexible displays, sensors and solar cells etc.

PMID- 24441982
TI  - Radial modulation doping in core-shell nanowires.
AB  - Semiconductor nanowires are potential candidates for applications in quantum
      information processing, Josephson junctions and field-effect transistors and
      provide a unique test bed for low-dimensional physical phenomena. The ability to
      fabricate nanowire heterostructures with atomically flat, defect-free interfaces
      enables energy band engineering in both axial and radial directions. The design
      of radial, or core-shell, nanowire heterostructures relies on energy band offsets
      that confine charge carriers into the core region, potentially reducing
      scattering from charged impurities on the nanowire surface. Key to the design of
      such nanoscale heterostructures is a fundamental understanding of the
      heterointerface properties, particularly energy band offsets and strain. The
      charge-transfer and confinement mechanism can be used to achieve modulation
      doping in core-shell structures. By selectively doping the shell, which has a
      larger bandgap, charge carriers are donated and confined in the core, generating
      a quasi-one-dimensional electron system with higher mobility. Here, we
      demonstrate radial modulation doping in coherently strained Ge-SixGe1-x core
      shell nanowires and a technique to directly measure their valence band offset.
      Radial modulation doping is achieved by incorporating a B-doped layer during
      epitaxial shell growth. In contrast to previous work showing site-selective
      doping in Ge-Si core-shell nanowires, we find both an enhancement in peak hole
      mobility compared with undoped nanowires and observe a decoupling of electron
      transport in the core and shell regions. This decoupling stems from the higher
      carrier mobility in the core than in the shell and allows a direct measurement of
      the valence band offset for nanowires of various shell compositions. 

PMID- 24441983
TI  - A surface-bound molecule that undergoes optically biased Brownian rotation.
AB  - Developing molecular systems with functions analogous to those of macroscopic
      machine components, such as rotors, gyroscopes and valves, is a long-standing
      goal of nanotechnology. However, macroscopic analogies go only so far in
      predicting function in nanoscale environments, where friction dominates over
      inertia. In some instances, ratchet mechanisms have been used to bias the ever
      present random, thermally driven (Brownian) motion and drive molecular diffusion
      in desired directions. Here, we visualize the motions of surface-bound molecular
      rotors using defocused fluorescence imaging, and observe the transition from
      hindered to free Brownian rotation by tuning medium viscosity. We show that the
      otherwise random rotations can be biased by the polarization of the excitation
      light field, even though the associated optical torque is insufficient to
      overcome thermal fluctuations. The biased rotation is attributed instead to a
      fluctuating-friction mechanism in which photoexcitation of the rotor strongly
      inhibits its diffusion rate. 

PMID- 24441984
TI  - Formation of a protected sub-band for conduction in quantum point contacts under
      extreme biasing.
AB  - Managing energy dissipation is critical to the scaling of current
      microelectronics and to the development of novel devices that use quantum
      coherence to achieve enhanced functionality. To this end, strategies are needed
      to tailor the electron-phonon interaction, which is the dominant mechanism for
      cooling non-equilibrium ('hot') carriers. In experiments aimed at controlling the
      quantum state, this interaction causes decoherence that fundamentally disrupts
      device operation. Here, we show a contrasting behaviour, in which strong electron
      phonon scattering can instead be used to generate a robust mode for electrical
      conduction in GaAs quantum point contacts, driven into extreme non-equilibrium by
      nanosecond voltage pulses. When the amplitude of these pulses is much larger than
      all other relevant energy scales, strong electron-phonon scattering induces an
      attraction between electrons in the quantum-point-contact channel, which leads to
      the spontaneous formation of a narrow current filament and to a renormalization
      of the electronic states responsible for transport. The lowest of these states
      coalesce to form a sub-band separated from all others by an energy gap larger
      than the source voltage. Evidence for this renormalization is provided by a
      suppression of heating-related signatures in the transient conductance, which
      becomes pinned near 2e(2)/h (e, electron charge; h, Planck constant) for a broad
      range of source and gate voltages. This collective non-equilibrium mode is
      observed over a wide range of temperature (4.2-300 K) and may provide an
      effective means to manage electron-phonon scattering in nanoscale devices.

PMID- 24441985
TI  - A nanophotonic solar thermophotovoltaic device.
AB  - The most common approaches to generating power from sunlight are either
      photovoltaic, in which sunlight directly excites electron-hole pairs in a
      semiconductor, or solar-thermal, in which sunlight drives a mechanical heat
      engine. Photovoltaic power generation is intermittent and typically only exploits
      a portion of the solar spectrum efficiently, whereas the intrinsic
      irreversibilities of small heat engines make the solar-thermal approach best
      suited for utility-scale power plants. There is, therefore, an increasing need
      for hybrid technologies for solar power generation. By converting sunlight into
      thermal emission tuned to energies directly above the photovoltaic bandgap using
      a hot absorber-emitter, solar thermophotovoltaics promise to leverage the
      benefits of both approaches: high efficiency, by harnessing the entire solar
      spectrum; scalability and compactness, because of their solid-state nature; and
      dispatchablility, owing to the ability to store energy using thermal or chemical
      means. However, efficient collection of sunlight in the absorber and spectral
      control in the emitter are particularly challenging at high operating
      temperatures. This drawback has limited previous experimental demonstrations of
      this approach to conversion efficiencies around or below 1% (refs 9, 10, 11).
      Here, we report on a full solar thermophotovoltaic device, which, thanks to the
      nanophotonic properties of the absorber-emitter surface, reaches experimental
      efficiencies of 3.2%. The device integrates a multiwalled carbon nanotube
      absorber and a one-dimensional Si/SiO2 photonic-crystal emitter on the same
      substrate, with the absorber-emitter areas optimized to tune the energy balance
      of the device. Our device is planar and compact and could become a viable option
      for high-performance solar thermophotovoltaic energy conversion.

PMID- 24441986
TI  - Word sense disambiguation in the clinical domain: a comparison of knowledge-rich
      and knowledge-poor unsupervised methods.
AB  - OBJECTIVE: To evaluate state-of-the-art unsupervised methods on the word sense
      disambiguation (WSD) task in the clinical domain. In particular, to compare graph
      based approaches relying on a clinical knowledge base with bottom-up topic
      modeling-based approaches. We investigate several enhancements to the topic
      modeling techniques that use domain-specific knowledge sources. MATERIALS AND
      METHODS: The graph-based methods use variations of PageRank and distance-based
      similarity metrics, operating over the Unified Medical Language System (UMLS).
      Topic-modeling methods use unlabeled data from the Multiparameter Intelligent
      Monitoring in Intensive Care (MIMIC II) database to derive models for each
      ambiguous word. We investigate the impact of using different linguistic features
      for topic models, including UMLS-based and syntactic features. We use a sense
      tagged clinical dataset from the Mayo Clinic for evaluation. RESULTS: The topic
      modeling methods achieve 66.9% accuracy on a subset of the Mayo Clinic's data,
      while the graph-based methods only reach the 40-50% range, with a most-frequent
      sense baseline of 56.5%. Features derived from the UMLS semantic type and concept
      hierarchies do not produce a gain over bag-of-words features in the topic models,
      but identifying phrases from UMLS and using syntax does help. DISCUSSION:
      Although topic models outperform graph-based methods, semantic features derived
      from the UMLS prove too noisy to improve performance beyond bag-of-words.
      CONCLUSIONS: Topic modeling for WSD provides superior results in the clinical
      domain; however, integration of knowledge remains to be effectively exploited.

PMID- 24441987
TI  - From the editor.

PMID- 24441988
TI  - Scientific literacy: a goal of educating people in and for the health
      professions.
AB  - Scientific literacy driven by the underlying habits of scientific thinking should
      be the focus of educating people in the health professions. This article
      identifies 23 characteristics of scientific thinking as well as other concepts
      relevant to scientific literacy. Examples are provided as to how these
      characteristics and concepts apply to the work of medical lab technicians, nurses
      and medical researchers. 

PMID- 24441989
TI  - The influence of conceptual models on work in occupational therapy history.
AB  - The concept of work has been close to the core of occupational therapy theory and
      practice since the foundation of the profession in the early part of this
      century. The way in which occupational therapists have dealt with this area of
      occupational performance, however, has been quite diverse. Current work programs
      in occupational therapy practice have evolved from struggles characterized by the
      influence of holistic and reductionistic thinking. The holistic view inherited
      from moral treatment formed the very base upon which the emerging profession was
      built. The external world in which occupational therapy grew demanded
      reductionism for validation due to the influence of the medical model in all
      areas of practice. This struggle contributed to the separation of pre-vocational
      training as the domain of Occupational Therapy, and vocational training as the
      domain of Vocational Rehabilitation. This article describes the struggle that
      resulted from this separation and chronicles the profession's attempt to keep
      holism in this area of practice. 

PMID- 24441990
TI  - Education and training programs for the prevention of work injuries: do they
      work?
AB  - Education and training programs are popular approaches to deal with the
      prevention of occupational injuries and diseases. Although they are one of the
      less preferred injury control options, they can be effective in reducing risk and
      injury when used in combination with other control systems. An examination of the
      literature evaluating the effectiveness of injury prevention programs,
      particularly associated with back injury, is presented. Format, structure and
      content of programs is discussed and applied to a model addressing behaviour
      change (the Health Belief Model). This model is used to suggest ways of improving
      education and training programs to ensure the development and maintenance of
      behaviour change. 

PMID- 24441991
TI  - Workers' compensation in New South Wales Australia: the OTS role.
AB  - Workers' compensation in New South Wales Australia, changed in 1987 to emphasise
      rehabilitation back into the workforce. This change has expanded the field in
      which occupational therapists can contribute to work-related injuries. The
      Occupational Therapists' wide ranging approach to workers with injuries, and
      their ability to take a multifactorial approach to problem solving, puts them in
      a good position to resolve complex issues relating to return to work. 

PMID- 24441992
TI  - Supported employment: principles and practices for interdisciplinary
      collaboration.
AB  - This article provides an overview of the philosophical and practical aspects of
      supported employment. The authors describe: (1) the primary supported employment
      clientele; (2) the disciplines and professions involved in delivering community
      based employment services for the population; and (3) selected intervention
      strategies that maximize supported employees' job tenure and satisfaction.
      Guidelines for interdisciplinary collaboration in identifying and implementing
      supported employment services are offered. 

PMID- 24441993
TI  - Worker's compensation, litigation, and employment factors in return to work.
AB  - The purpose of this paper is to provide a critical review of three variables
      considered important in the return to work of a worker with a low-back injury.
      These are: (1) worker's compensation; (2) litigation; and (3) employment factors,
      including length of time at pre-injury employment, availability of a job after
      injury, and duration of time off work due to low-back pain. Although the
      literature is inconclusive regarding the effects of worker's compensation,
      research suggests that litigation, pre-morbid employment, length of unemployment
      due to disability, and availability of a job following injury impact on
      employment prognosis after rehabilitation. 

PMID- 24441994
TI  - Wrist postures in video display terminal operators (VDT) using different
      keyboards.
AB  - This study examined the differences in wrist motion using three types of
      keyboards: a standard QWERTY design and two alternative designs, the Truform
      Ergonomic keyboard and the Health Care Comfort keyboard. The Comfort keyboard
      (adjusted at a lateral slope of 30 degrees  and horizontal split of 20 degrees 
      and the Truform keyboard (with a 20 degrees  horizontal split) were compared with
      the standard flat QWERTY keyboard. Twenty adult video display terminal (VDT)
      workers from the Boston area ranging from 22 to 68 years of age volunteered to
      participate in this study. In randomly assigned sequences, participants typed for
      5 min on each keyboard while their wrist motions were measured using the
      WristSystem by Greenleaf Medical Systems, Inc. Contrast score analysis was used
      to analyze mean values in flexion-extension and radial-ulnar deviation of the
      right and left hands between the three sessions. The alternative keyboards
      significantly reduced ulnar deviation (left: t(19) = 3.46, P < 0.0025; right:
      t(19) = 5.83, P < 0.00001), and extension (left: t(19) = 2.82, P < 0.001; right:
      t(19) = 3.99, P < 0.0005). Results suggest that the Comfort keyboard yielded less
      ulnar deviation and extension as compared to the standard QWERTY keyboard (Left
      Extension: QWERTY mean = 21.45, Comfort mean = 18.67; Right Extension: QWERTY
      mean = 22.9, Comfort mean = 14.45; Left Ulnar Deviation: QWERTY mean = 14.54,
      Comfort mean = 7.44; Right Ulnar Deviation: QWERTY mean = 17.1, Comfort mean =
      6.12). Although the Truform keyboard reduced ulnar deviation (Left: QWERTY mean =
      14.54, Truform mean = 9.42; Right: QWERTY mean = 17.1, Truform mean = 9.67), it
      also yielded extension values comparable to those using the QWERTY (Left
      Extension: QWERTY mean = 21.45, Truform mean = 24.66; Right Extension: QWERTY
      mean = 22.9; Truform mean = 22.4). Both alternative designs yielded slightly
      higher values for radial deviation (left: t(19)=-2.4, P > 0.25; right: t(19)=
      3.75, P > 0.25) and flexion (left: t(19)=-1.39, P > 0.25; right: t(19)=-3.75, P >
      0.25). Still, these increases remained well within the 'neutral' zone (< 15-20
      degrees ). The results suggest that among the three keyboard designs, the Comfort
      keyboard was the most effective in maintaining a neutral wrist posture. Although
      the Truform significantly reduced ulnar devation, it also yielded extension
      values beyond the neutral range (> 15 degrees ). Clinically, these findings may
      assist occupational therapists in suggesting appropriate keyboard designs during
      workstation ergonomic modification or consultation. Further research is needed to
      reinforce these findings. 

PMID- 24441995
TI  - Hand care begins with prevention in elementary schools.
AB  - OBJECTIVES: The purpose of this paper is to provide background information on the
      epidemic proportions of hand injuries related to computer use. It offers a
      solution of early health education in prevention of cumulative trauma disorders
      (CTDs) through specially designed instruction in elementary schools. STUDY
      DESIGN: The current literature is reviewed. Some physical impairments caused by
      poor biomechanics and computer overuse are identified. Disability factors are
      highlighted in relation to how the physical impairment affects an individual's
      performance in the domain of work. Handicapping factors that are the result of
      the individual's decline in performance roles of worker are noted. These factors
      impact our society in dollars spent on medical insurance and worker's
      compensation claims. A review of a pilot project aimed at early education in hand
      health basics is introduced, as a proactive ergonomic solution to the present
      epidemic of cumulative trauma disorders. RESULTS: A positive response was
      displayed by the 950 elementary students and their staff to a 20-min program that
      introduced concepts of posture at the keyboard and basic upper body stretches.
      Children were instructed in their individual classes during their computer lab
      time. Daily follow-up, particularly for the forearm and hand stretches, was
      fostered by the computer lab coordinator, teachers, and wall posters. Parents
      were informed through a summary article printed in the monthly school newsletter.
      CONCLUSIONS: Wellness thinking and living can be learned at an early age to
      assure that basic principles of work practice such as posture and upper body
      stretches become a life skill. Review of the literature supports programs to
      educate individuals at an early age to develop life skills that would minimize
      the occurrence of cumulative trauma disorders, especially in relation to the use
      of computers.

PMID- 24441996
TI  - Cumulative trauma disorders among hand therapists.
AB  - OBJECTIVES: This study examined the prevalence of cumulative trauma disorders
      (CTDs) among hand therapists. Factors such as hand therapy tasks and number of
      years spent performing these tasks were examined in their contribution to CTD
      symptoms of the upper extremity. STUDY DESIGN: Of the 356 questionnaires
      distributed to registrants at the 1996 Hand Conference, 195 (55%) were returned.
      A t-test was used to determine whether the number of years spent practicing hand
      therapy was a significant factor in the development of CTD symptoms among hand
      therapists. RESULTS: Of the 195 respondents, 73% reported they had previously
      experienced CTD symptoms, and 46% reported they were currently experiencing CTD
      symptoms. A significant difference was found (P < 0.05) in the development of CTD
      symptoms with regard to number of years practiced. CONCLUSION: The work practices
      of hand therapists place them at risk for developing CTDs. Hand therapists who
      spend more years practicing are more likely to incur CTDs.

PMID- 24441998
TI  - Witness: the truth please.

PMID- 24441997
TI  - Animal assisted therapy for children and adolescents with disabilities.
AB  - This article provides an overview of animal assisted therapy, or the use of
      animals as a treatment modality, specifically with children and adolescents.
      Animal assisted therapy is defined within the context of occupational therapy,
      and its benefits on the communicative, psychosocial, and academic/pre-vocational
      functioning of youths with disabilities are explored. The paper concludes with
      resources, including organizations specializing in the advancement of animal
      assisted therapy as well as literature explaining how to create and implement a
      program within one's existing practice. 

PMID- 24441999
TI  - Restore, a user-friendly system.

PMID- 24442000
TI  - The immunization and vaccine crisis in developing countries.
AB  - Health care research has shown that immunization can play a crucial role in
      fighting infectious diseases. A global effort was launched to decrease the
      incidence of infectious disease worldwide through immunization. This paper
      highlights many of the problems which have contributed to an immunization crisis,
      in which developing countries are not receiving the benefits of vaccines due to
      slow vaccine delivery systems; the increasing cost of vaccines; and vaccine and
      immunization program deficiencies. Consequences of the crisis, solutions, and the
      role of health care professionals in supporting immunization programs are
      presented. 

PMID- 24442001
TI  - Author indexVolume 9 (1997).

PMID- 24442003
TI  - Volume contentsVolume 9 (1997).

PMID- 24442004
TI  - Does modality of adjuvant chemotherapy after interval surgical debulking matter
      in epithelial ovarian cancer?: An exploratory analysis.
AB  - OBJECTIVES: This article aimed to study the role of adjuvant intraperitoneal (IP)
      chemotherapy after neoadjuvant chemotherapy and optimal interval surgical
      debulking. METHOD: All patients with epithelial ovarian cancer treated with
      neoadjuvant chemotherapy were retrospectively reviewed from 2007 to 2009.
      Demographics, related diseases, and survival outcome data were abstracted from
      the medical records. chi statistics were applied to categorical variables. Cox
      regression was used to model progression-free survival (PFS), adjusting for age,
      residual status, and use of adjuvant IP chemotherapy. All P values less than 0.05
      were considered statistically significant. RESULTS: Sixty-five patients were
      reviewed. The median age was 63.3 years. The majority had stage III disease with
      serous histology. Optimal residual (<1 cm) after interval debulking was achieved
      in 34 (54%) of 63 patients. Sixteen patients chose to receive adjuvant IP
      chemotherapy. The median follow-up was 26.2 months. Fifty-one patients had
      progressed, with a median PFS of 17.5 months. Adjuvant IP chemotherapy was not
      predictive of PFS (hazard ratio, 0.91; 95% confidence interval [CI], 0.24-3.44; P
      = 0.89). The estimated median overall survival was 37.8 months (95% CI, 29.9
      45.7) in the intravenous group versus 48.1 months (95% CI, 37.9-58.3) in the IP
      treated patients (P = 0.162). CONCLUSIONS: Adjuvant IP chemotherapy was not
      predictive of survival after neoadjuvant chemotherapy in our small exploratory
      study. The role of IP chemotherapy in this setting needs to be further studied in
      a larger prospective patient cohort.

PMID- 24442005
TI  - Analysis of the prognosis and related factors for patients with stage IV
      gestational trophoblastic neoplasia.
AB  - OBJECTIVE: This study aimed to investigate and analyze the treatments and
      prognoses of patients with stage IV gestational trophoblastic neoplasia (GTN).
      METHODS: Between January 1990 and January 2010, 105 patients with stage IV GTN
      were treated in our hospital (Peking Union Medical College Hospital). A
      retrospective study is presented herein to report the prognoses of these patients
      and to statistically analyze the risk factors that affected the prognoses of
      patients with stage IV GTN. RESULTS: After the treatments, of the 105 patients,
      71 (67.6%) patients achieved complete remission, 15 (14.3%) patients exhibited
      partial remission, and 19 (18.1%) patients exhibited progression of the disease.
      In total, of the 105 patients, 30 (28.6%) patients died. Our statistical analyses
      have revealed that a previously failed multidrug chemotherapy history, multiorgan
      metastasis concomitant with renal metastasis, and surgical intervention all
      affected the prognoses of patients with stage IV GTN. In addition, patients with
      stage IV GTN with International Federation of Gynecology and Obstetrics scores
      below 12 were relatively more likely to obtain complete remission. CONCLUSIONS:
      Multidrug, multiroute chemotherapy, assisted by surgery when necessary, is the
      predominant strategy for patients with stage IV GTN. Fluorouracil-based multidrug
      chemotherapy can produce good outcomes for patients with stage IV GTN who were
      treated primarily. Adequate attention should be given to patients who have
      previously failed multidrug chemotherapy, have experienced multiorgan metastasis
      concomitant with renal metastasis, or have International Federation of Gynecology
      and Obstetrics scores of more than 12.

PMID- 24442006
TI  - Survival after curative pelvic exenteration for primary or recurrent cervical
      cancer: a retrospective multicentric study of 167 patients.
AB  - OBJECTIVE: Evaluate the survival of patients who underwent pelvic exenteration
      (PE) with curative intent for primary persistent or recurrent cervical cancer.
      METHODS: We retrospectively investigated 167 consecutive patients, referred to
      the gynecological oncology units of 4 centers in Germany or Italy, who underwent
      PE. Data regarding surgery, histology, and oncologic outcomes were collected and
      statistically evaluated. Survival was determined from the day of exenteration
      until last follow-up or death. RESULTS: The median age was 51 years. Twenty-seven
      patients (16.2%) underwent PE owing to advanced primary tumors (group A), 34
      patients (20.4%) underwent PE owing to persistent cancer after chemotherapy or
      chemoradiation (group B), and 106 patients (63.4%) underwent PE owing to
      recurrence (group C). The prevalent histologic type was squamous cell cancer. A
      complete tumor resection (R0), was achieved in 121 patients (72.5%). Forty-nine
      patients (29.3%) had pelvic lymph node metastases and 44 patients (26.3%) had
      pelvic sidewall involvement. Overall survival at the end of the study was 40.7%.
      The cumulative 5-year overall survival for the entire cohort was 38%. Resection
      margins, pelvic lymph node state, and sidewall involvement were independent
      prognostic factors in multivariate analysis. CONCLUSION: Pelvic exenteration is a
      valid therapeutic option for patients with locally advanced primary persistent or
      recurrent cervical cancer, with a long-term survival in 40% of the patients.

PMID- 24442009
TI  - Molecular spectroscopy from near-infrared to terahertz wavelengths--more than
      just good vibrations: Seventh International Conference on Advanced Vibrational
      Spectroscopy (ICVAS 7).

PMID- 24442007
TI  - Visualizing structural dynamics of thylakoid membranes.
AB  - To optimize photosynthesis, light-harvesting antenna proteins regulate light
      energy dissipation and redistribution in chloroplast thylakoid membranes, which
      involve dynamic protein reorganization of photosystems I and II. However, direct
      evidence for such protein reorganization has not been visualized in live cells.
      Here we demonstrate structural dynamics of thylakoid membranes by live cell
      imaging in combination with deconvolution. We observed chlorophyll fluorescence
      in the antibiotics-induced macrochloroplast in the moss Physcomitrella patens.
      The three-dimensional reconstruction uncovered the fine thylakoid membrane
      structure in live cells. The time-lapse imaging shows that the entire thylakoid
      membrane network is structurally stable, but the individual thylakoid membrane
      structure is flexible in vivo. Our observation indicates that grana serve as a
      framework to maintain structural integrity of the entire thylakoid membrane
      network. Both the structural stability and flexibility of thylakoid membranes
      would be essential for dynamic protein reorganization under fluctuating light
      environments. 

PMID- 24442008
TI  - Re-exploring the high-throughput potential of microextraction techniques, SPME
      and MEPS, as powerful strategies for medical diagnostic purposes. Innovative
      approaches, recent applications and future trends.
AB  - The human population continues to grow exponentially in the fast developing and
      most populated countries, whereas in Western Europe it is getting older and older
      each year. This inevitably raises the demand for better and more efficient
      medical services without increasing the economic burden in the same proportion.
      To meet these requirements, improvement of medical diagnosis is certainly a key
      aspect to consider. Therefore, we need powerful analytical methodologies able to
      go deeper and further in the characterization of human metabolism and
      identification of disease biomarkers and endogenous molecules in body fluids and
      tissues. The ultimate goal is to have a reliable and early medical diagnosis,
      mitigating the disease complications as much as possible. Microextraction
      techniques (METs) represent a key step in these analytical methodologies by
      providing samples in the suitable volumes and purification levels necessary for
      the characterization of the target analytes. In this aspect, solid-phase
      microextraction (SPME) and, more recently, microextraction by packed sorbent
      (MEPS), are powerful sample preparation techniques, characterized by their
      reduced time of analysis, low solvent consumption, and broad application.
      Moreover, as miniaturized techniques, they can be easily automatized to have a
      high-throughput performance in the clinical environment. In this review, we
      explore some of the most interesting MEPS and SPME applications, focusing on
      recent trends and applications to medical diagnostic, particularly the in vivo
      and near real time applications. 

PMID- 24442010
TI  - Aggressive dereplication using UHPLC-DAD-QTOF: screening extracts for up to 3000
      fungal secondary metabolites.
AB  - In natural-product drug discovery, finding new compounds is the main task, and
      thus fast dereplication of known compounds is essential. This is usually
      performed by manual liquid chromatography-ultraviolet (LC-UV) or visible light
      mass spectroscopy (Vis-MS) interpretation of detected peaks, often assisted by
      automated identification of previously identified compounds. We used a 15 min
      high-performance liquid chromatography-diode array detection (UHPLC-DAD)-high
      resolution MS method (electrospray ionization (ESI)(+) or ESI(-)), followed by 10
      60 s of automated data analysis for up to 3000 relevant elemental compositions.
      By overlaying automatically generated extracted-ion chromatograms from detected
      compounds on the base peak chromatogram, all major potentially novel peaks could
      be visualized. Peaks corresponding to compounds available as reference standards,
      previously identified compounds, and major contaminants from solvents, media,
      filters etc. were labeled to differentiate these from compounds only identified
      by elemental composition. This enabled fast manual evaluation of both known peaks
      and potential novel-compound peaks, by manual verification of: the adduct
      pattern, UV-Vis, retention time compared with log D, co-identified biosynthetic
      related compounds, and elution order. System performance, including adduct
      patterns, in-source fragmentation, and ion-cooler bias, was investigated on
      reference standards, and the overall method was used on extracts of Aspergillus
      carbonarius and Penicillium melanoconidium, revealing new nitrogen-containing
      biomarkers for both species. 

PMID- 24442011
TI  - HPLC-UV-ESI MS/MS identification of the color constituents of sawwort (Serratula
      tinctoria L.).
AB  - Extracts from wool dyed with sawwort (Serratula tinctoria L.) obtained with
      methanol/formic acid and methanol/hydrochloric acid solutions were examined by
      high-performance liquid chromatography with UV detection coupled with
      electrospray ionization tandem mass spectrometry. Chromatograms and mass spectra
      were registered in the negative ion mode under various orifice voltages and
      collision energies, which enabled us to observe signals corresponding to [M - H](
      ) ions and also Y(-) and/or Y(-*) ions, which were further subjected to
      fragmentation. The results obtained allowed us to define previously unknown
      constituents of sawwort, which are proposed as specific markers for its
      identification: chlorogenic acid and its isomers, luteolin-O-glucuronides,
      eriodictyol-O-glucuronides, and diosmetin-O-glucuronides. Moreover, it was found
      that during extraction, flavonoid O-glucuronides react with methanol in the
      presence of hydrochloric acid, forming stable O-methylated derivatives. 

PMID- 24442012
TI  - A colorimetric indicator-displacement assay array for selective detection and
      identification of biological thiols.
AB  - A simple, inexpensive yet highly selective colorimetric indicator-displacement
      assay array for the simultaneous detection and identification of three important
      biothiols at micromolar concentrations under physiological conditions and in real
      samples has been developed in this work. With use of an array composed of metal
      indicators and metal ions, clear differentiation among cysteine, homocysteine and
      glutathione was achieved. On the basis of the colour change of the array,
      quantification of each analyte was accomplished easily, and different biothiols
      were identified readily using standard chemometric approaches (hierarchical
      clustering analysis). Moreover, the colorimetric sensor array was not responsive
      to changes with 19 other natural amino acids, and it showed excellent
      reproducibility. Importantly, the sensor array developed was successfully applied
      to the determination and identification of the three biothiols in a real
      biological sample. 

PMID- 24442013
TI  - Field-flow fractionation.

PMID- 24442014
TI  - On-line species-unspecific isotope dilution analysis in the picomolar range
      reveals the time- and species-depending mercury uptake in human astrocytes.
AB  - In order to reveal the time-depending mercury species uptake by human astrocytes,
      a novel approach for total mercury analysis is presented, which uses an
      accelerated sample introduction system combined on-line with an inductively
      coupled plasma mass spectrometer equipped with a collision/reaction cell. Human
      astrocyte samples were incubated with inorganic mercury (HgCl2), methylmercury
      chloride (MeHgCl), and thimerosal. After 1-h incubation with Hg(2+), cellular
      concentrations of 3 MUM were obtained, whereas for organic species,
      concentrations of 14-18 MUM could be found. After 24 h, a cellular accumulation
      factor of 0.3 was observed for the cells incubated with Hg(2+), whereas the
      organic species both showed values of about 5. Due to the obtained steady-state
      signals, reliable results with relative standard deviations of well below 5 % and
      limits of detection in the concentration range of 1 ng L(-1) were obtained using
      external calibration and species-unspecific isotope dilution analysis approaches.
      The results were further validated using atomic fluorescence spectrometry. 

PMID- 24442016
TI  - From the editor.

PMID- 24442017
TI  - Marketing work practices.

PMID- 24442015
TI  - Ligation-triggered fluorescent silver nanoclusters system for the detection of
      nicotinamide adenine dinucleotide.
AB  - Herein, we demonstrate a novel silver nanocluster-based fluorescent system for
      the detection of nicotinamide adenine dinucleotide (NAD(+)), an important
      biological small molecule involved in a wide range of biological processes. A
      single-stranded dumbbell DNA probe was designed and used for the assay, which
      contained a nick in the stem, a poly-cytosine nucleotide loop close to 5' end as
      the template for the formation of highly fluorescent silver nanoclusters (Ag NCs)
      and another loop close to 3' end. Only in the presence of NAD(+), the probe was
      linked at 5' and 3' ends by Escherichia coli DNA ligase, which blocked the DNA
      polymerase-based extension reaction, ensuring the formation of fluorescent Ag
      NCs. This technique provided a logarithmic linear relationship in the range of 1
      pM-500 nM with a detection limit of as low as 1 pM NAD(+), and exhibited high
      selectivity against its analogues, and was then successfully used for the
      detection of NAD(+) level in four kinds of cell homogenates. In addition, this
      new approach was conducted in an isothermal and homogeneous condition without the
      need of any thermal cycling, washing, and separation steps, making it very
      simple. Overall, this label-free protocol offers a promising alternative for the
      detection of NAD(+), taking advantage of specificity, sensitivity, cost
      efficiency, and simplicity. 

PMID- 24442018
TI  - Marketing ADA Compliance to University CampusesOccupational Therapist's Role.

PMID- 24442019
TI  - Marketing's Role in Work Programs.

PMID- 24442020
TI  - The value-added approach to marketing.

PMID- 24442022
TI  - Hospital-Based Wellness ProgramsA Profit Center for Occupational Health Services.

PMID- 24442021
TI  - Developing and marketing an ergonomics program in a corporate office environment.

PMID- 24442023
TI  - Marketing Supported EmploymentMainstream Jobs for Persons with the Most Severe
      Disabilities.

PMID- 24442024
TI  - Marketing Work ProgramsA Consumer-Based Approach.

PMID- 24442025
TI  - Advantage health systems, inc.offering industry the advantage.

PMID- 24442026
TI  - MarketingA Natural for Good Rehabilitation Providers.

PMID- 24442027
TI  - Predetermined Motion-Time Standards in RehabilitationA Review.

PMID- 24442028
TI  - Industrial therapy breaking down the barriers.

PMID- 24442029
TI  - Practice what we teach.

PMID- 24442031
TI  - The 2D Static Strength Prediction ProgramTM.

PMID- 24442032
TI  - Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal
      antibody targeting HER3, in Japanese patients with advanced solid tumors.
AB  - PURPOSE: Patritumab (U3-1287) is a human epidermal growth factor receptor-3
      (HER3)-targeted antibody that blocks ligand-associated activation of HER3. This
      open-label, phase 1 and dose-finding study (ClinicalTrials.jp Identifier:
      JapicCTI-101262) aimed to assess the safety, pharmacokinetics, incidence of anti
      patritumab antibody, recommended dose for subsequent clinical studies,
      preliminary efficacy, and patritumab-related biomarkers in Japanese patients with
      advanced solid tumors. METHODS: Patients received patritumab 9 or 18 mg/kg
      intravenously every 3 weeks until disease progression or intolerable toxicity
      occurred. Adverse events (AEs) were assessed according to the National Cancer
      Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
      Dose-limiting toxicities (DLTs) were evaluated from the initial dose to Cycle 1
      Day 21. Tumor response was assessed with Response Evaluation Criteria in Solid
      Tumors (RECIST version 1.1). RESULTS: Nine patients received patritumab 9 mg/kg
      (n = 3) or 18 mg/kg (n = 6). Five patients were male, all patients had Eastern
      Cooperative Oncology Group performance status (PS) <= 1, and median (range) age
      of 67 (50-69) years. No DLTs were reported. Patritumab-related AEs reported in
      >=2 patients were ALT increase (three patients), thrombocytopenia, diarrhea,
      stomatitis, cheilitis, rash maculo-papular and AST increase (two each).
      Pharmacokinetics profile was similar to the preceding US phase 1 study. Soluble
      HER3 concentration in serum unexpectedly increased in all patients. These changes
      did not correlate with clinical response. Four patients had a best response of
      stable disease. All patients tested had negative for anti-patritumab antibody
      formation. CONCLUSIONS: Patritumab was well tolerated up to 18 mg/kg without DLTs
      in Japanese patients with advanced solid tumors. Soluble HER3 increased in all
      patients.

PMID- 24442034
TI  - Intravesical thermo-chemotherapy based on conductive heat: a first
      pharmacokinetic study with mitomycin C in superficial transitional cell carcinoma
      patients.
AB  - PURPOSE: To evaluate, for the first time, the mitomycin C (MMC) pharmacokinetics
      during intravesical hyperthermia treatment based on conductive heat and the
      stability and recovery of the drug at the end of the instillation period.
      METHODS: Eleven patients with recurrent intermediate-risk superficial
      transitional cell carcinoma of the bladder were treated weekly for six cycles
      with intravesical MMC (40 mg MMC in 50 ml) in local hyperthermia (45  degrees C)
      with Unithermia((r)) system. Each instillation lasted 45 min, with the solution
      being replaced after the first 22 min. The MMC recovery at the end of the two
      instillation period and the plasmatic pharmacokinetics of MMC were evaluated by
      high-pressure liquid chromatography. RESULTS: Nine patients completed all the six
      planned cycles, whereas two patients missed the last cycle because of allergic
      reactions. No other systemic toxicity was observed, and the local toxicities were
      mild. Median MMC concentration in the instillation residual solution decreases
      from the initial 0.8 to 0.22 mg/ml for the 0-22-min instillation period and to
      0.38 mg/ml for the 22-45-min instillation period; the median percentage of MMC
      recovered after instillation was 66.2 and 99.6, respectively. In all patients,
      MMC plasmatic C max resulted considerably lower than the toxic threshold (400
      ng/ml). CONCLUSIONS: The MMC is stable during the instillation, and its
      absorption occurs mainly during the first minutes of the treatment. The plasmatic
      MMC concentration is always well below the threshold level for myelosuppression,
      as confirmed by the total lack of hematological toxicity evidenced by the
      patients. In order to evaluate the efficacy of the treatment performed with
      UniThermia((r)) in reducing the disease recurrence rate in short- and long-term
      follow-up, we are currently carrying out a clinical multicentric study involving
      a larger number of patients.

PMID- 24442033
TI  - Age affects pegylated liposomal doxorubicin elimination and tolerability in
      patients over 70 years old.
AB  - PURPOSE: Pegylated liposomal doxorubicin (PLD) is often used in elderly people,
      due to its improved tolerability. However, clinical and pharmacological data in
      the subset of patients over 70 are scanty. METHODS: PLD safety was evaluated in
      35 patients (aged >=70 years) who were treated with PLD as a single agent for 165
      cycles. Doxorubicin plasma levels, leukocyte DNA breaks and monocyte count
      variations were measured as markers of drug exposure, DNA repair capability and
      reticuloendothelial system activation, respectively. A correlation between these
      markers and age was sought. RESULTS: Treatment was generally well tolerated. Skin
      erythrodysesthesia was the most frequent side effect, and no severe (G4) toxicity
      occurred. PLD plasma half-life generally correlated with age (P < 0.001) and was
      particularly prolonged in octogenarians (P = 0.005). Doxorubicin clearance
      significantly declined up to 70 % at cycle 7. DNA breaks increased over the first
      two cycles (P = 0.007) and were inversely correlated with age (P = 0.007) and
      directly with clearance (P = 0.006). Pre-treatment monocyte counts increased over
      cycles (P < 0.001) and were associated with an increase in clearance at cycle 3
      (P = 0.015). The hand-foot-skin syndrome was significantly more severe in
      patients of advanced age or longer PLD half-life. CONCLUSIONS: This study showed
      (1) increased systemic drug exposure over subsequent cycles; (2) association of
      age with increased drug exposure, reduced DNA repair capability and worse skin
      toxicity; (3) a relation between monocyte count and drug clearance.

PMID- 24442035
TI  - Mycology: an update.

PMID- 24442036
TI  - Immune resistance and tolerance to fungi.
AB  - Fungal diseases represent an important paradigm in immunology, since they can
      result from either the lack of recognition or over-activation of the inflammatory
      response. Current understanding of the pathophysiology underlying fungal
      infections and diseases highlights the multiple cell populations and cell
      signaling pathways involved in these complex conditions beyond the dysregulated
      chaos in which fungal infection and disease are perceived. A systems biology
      approach that integrates investigations of immunity at the systems-level is
      required to generate novel insights into this complexity and to decipher the
      dynamics of the host-fungus interaction. Recent advances in the immune response
      to fungi have highlighted the cellular and molecular mechanisms of immune
      adaptations that maintain homeostasis with the fungal biota and its possible
      rupture in fungal infections and diseases. Functionally distinct modules of
      immunity, i.e., resistance and tolerance, evolved for the achievement of the best
      fitted host-fungus interaction in mammals, are now essential components of the
      host-fungus interaction in the vertebrate host. 

PMID- 24442037
TI  - Dermatophytosis in animals: epidemiological, clinical and zoonotic aspects.
AB  - AIM: Dermatophytosis are the most frequent fungal infections of pets and
      livestock and play an important role in animal and human health due to their
      zoonotic potential. Another important aspect of these infections is linked to the
      economic consequences in farm animal and fur production systems. An overview of
      dermatophytosis in animals is described in this paper. Epidemiological, clinical
      and zoonotic aspects are addressed, considering individual species, both pets and
      farmed animals. METHODS: In particular, most recent investigations in the field
      of animal mycology, carried out in Central Italy, are reported, with particular
      reference to rabbit, ruminants, horse, dog, cat and some wild species. RESULTS:
      The information in this article show how dermatophytes infect a wide range of
      animals which may be in contact with human beings either directly or indirectly.
      Consequently they are frequently a source of infection for human beings who, vice
      versa, may sometimes become contagious for animals. CONCLUSION: Fungal pathogens
      derive their power to spread from contamination of the animal's habitat - whether
      the animal is a conventional pet or not, a farm animal or living in the wild.
      Thus if treatment of the animal or human patient is to achieve optimal efficacy,
      it needs to be associated with adequate environmental measures.

PMID- 24442038
TI  - Migration and mycoses.
AB  - In recent years, the incidence of fungal infections of the skin, one of the most
      frequent forms of infection, has been steadily increasing in Europe. One of the
      main factors contributing to this increase is the gradual raise of migratory
      flows towards Europe. In the last decades Italy has witnessed an ever-increasing
      growth of the migrant population, and has become, to this day, one of the
      European countries with the highest number of immigrants. This phenomenon has had
      significant implications in clinical practice of dermatologic mycology as it is
      increasingly common to see unusual clinical isolate causal agents absent in our
      latitudes until a short time ago. This review provides an update on the
      epidemiology, classification, pathogenesis, clinical manifestations and treatment
      of the most important dermato-mycosis observed in the immigrant population,
      through the most typical cases, investigated by microscopic and cultural
      findings. These diseases continue to expand and are often difficult to detect.
      The special relationship between host-environment interaction-parasite plays a
      crucial role as, even more than in other categories, it is widely widespread
      among the immigrants. 

PMID- 24442039
TI  - Tinea atypica.
AB  - Although usually simple, the diagnosis of dermatophyte infection is sometimes
      neglected. Variations in clinical presentation (tinea atypica), mimicking other
      skin diseases depend on many factors, partially due to the dermatophyte's
      characteristics, and a combination of patient's pathological but often
      physiological conditions, such as excessive washing or sun exposure. The
      physician's misdiagnosis and eventual prescription of steroids or other
      incongruous treatments further induce pathomorphosis (tinea incognito),
      longstanding disease and delayed recovery. This review describes the morphology
      of some atypical dermatophyte infections, in an attempt to compare and correlate
      changes to the normal features of the disease by site of involvement. The risk
      factors and predisposing conditions are also analysed to provide a reasoned
      interpretation of morphology and therefore evoke the diagnostic suspect in
      atypical cases. Periodical training is the clue to improve dermatologist
      expertise in what is the first-sight ability to make a diagnosis, perform the
      correct assessments and consequent therapy in daily practice. 

PMID- 24442040
TI  - Skin and nail mycoses in patients with diabetic foot.
AB  - Diabetes mellitus affects all socioeconomic and age groups and its incidence is
      rapidly increasing worldwide. The diabetic foot complication represents one of
      the most complex and serious complications in these patients. Fungal infections
      can also contribute to the severity of the diabetic foot. The aim of the present
      study was to evaluate the prevalence of foot skin and toenail mycosis in a group
      of 75 patients with diabetic foot complication and in a matched control group.
      Diabetic patients showed onychomycosis in 53.3% and foot skin mycosis in 46.7% of
      the cases, with a prevalence of both fungal infections significantly higher than
      that observed in the control group. At least one type of these fungal infections
      was present in 69.3% of diabetic subjects with a highly significant difference
      compared to control group (P<0.001). Trichophyton rubrum and Trichophyton
      interdigitale were the most common species responsible of both nail and skin
      infections. Candida spp, Fusarium spp, Aspergillus spp and other moulds. were
      found in about 1/3 onychomycosis. Previous toe amputation was significantly
      associated with both skin and nail mycosis. The present study confirms that both
      tinea pedis and onychomycosis have a high prevalence in subjects suffering from
      diabetic foot complication, and that the problem of fungal infections of the foot
      in diabetic subjects is still highly underestimated. Consequently, there is an
      important clinical rationale for careful mycological examination of diabetic foot
      and an adequate treatment tailored for each individual patient according to the
      fungal species involved. 

PMID- 24442041
TI  - Malassezia skin diseases in humans.
AB  - Although Malassezia yeasts are a part of the normal microflora, under certain
      conditions they can cause superficial skin infection, such as pityriasis
      versicolor (PV) and Malassezia folliculitis. Moreover the yeasts of the genus
      Malassezia have been associated with seborrheic dermatitis and dandruff, atopic
      dermatitis, psoriasis, and, less commonly, with confluent and reticulated
      papillomatosis, onychomycosis, and transient acantholytic dermatosis. The study
      of the clinical role of Malassezia species has been surrounded by controversy due
      to the relative difficulty in isolation, cultivation, and identification. This
      review focuses on the clinical, mycologic, and immunologic aspects of the various
      skin diseases associated with Malassezia. Moreover, since there exists little
      information about the epidemiology and ecology of Malassezia species in the
      Italian population and the clinical significance of these species is not fully
      distinguished, we will report data about a study we carried out. The aim of our
      study was the isolation and the identification of Malassezia species in PV
      affected skin and non-affected skin in patients with PV and in clinically healthy
      individuals without any Malassezia associated skin disease. 

PMID- 24442042
TI  - Subcutaneous mycoses. Part 1: subcutaneous mycoses due to non-dermatophytes.
AB  - Subcutaenous mycoses are increasingly reported in the literature for various
      reasons. Firstly, life expectancy has increased and even patients with cancer
      and/or immunodepression live longer, making them susceptible to these infections.
      Secondly, diagnostic techniques for mycoses have improved. Dermatologists have
      now begun to suspect subcutaneous mycoses when faced with certain clinical
      pictures and are aware of the need for histopathological examination and culture
      of lesion biopsy material on appropriate culture media. This review considers the
      clinical, histopathological and mycological aspects of the most common
      subcutaneous mycoses and outlines how to treat them. A better understanding of
      these mycoses enables early diagnosis and treatment of infections that are
      sometimes life-threatening. 

PMID- 24442043
TI  - Update on the management of onychomycosis.
AB  - Onychomycosis is a fungal infection of the nail which is highly prevalent in the
      general population, particularly among older individuals. Patients seek care
      because the disease is infectious or simply for an esthetic discomfort. The
      difficulty in treating onychomycosis results from the deep-seated nature of the
      infection within the nail unit and the inability of drugs to effectively reach
      all sites. Present treatment options include both oral and topical drugs, with
      oral therapies giving better outcomes. New derivatives with a favorable risk
      benefit ratio and new formulations of older azoles seem to be promising. The
      research for new drugs or formulations has the objective of discovering new
      active antifungals or new technologies to facilitate incorporation or persistence
      of existing antifungal drugs inside the nail plate. In fact, the same
      antimycotics that heal skin fungal infections are rendered less efficacious in
      nail disease. This update has the aim to synthesize and focus the therapies
      currently in use and new therapeutic approaches on onychomycosis. It also
      summarizes the newer areas of research in the treatment of onychomycosis as
      photodynamic and laser therapy. 

PMID- 24442045
TI  - Psoriasis or "psoriases"?

PMID- 24442044
TI  - Photodynamic chemotherapy in the treatment of superficial mycoses: an evidence
      based evaluation.
AB  - Photodynamic therapy (PDT) is a constantly evolving treatment modality consisted
      of a chemical reaction activated by light energy that is used to selectively
      destroy tissue; it may be considered a particular form of photochemotherapy that
      uses a photosensitizer, light and oxygen. The combination of the possibility of
      ablation of lesion with an excellence aesthetic result has allowed the
      photodynamic therapy an increasing role in the treatment of skin disease, that
      ranges from skin cancer to cosmetic treatment. Particular attention is paid in
      the last years to a developing area of research, the antifungal photodynamic
      therapy. The growing resistance against antifungal drugs has renewed the search
      for alternative therapies and PDT seems to be a potential candidate. This article
      provides an extensive review of antifungal photodynamic therapy, its mechanisms
      and applications in the treatment of superficial mycoses. 

PMID- 24442046
TI  - Topical steroids and corticophobia.

PMID- 24442047
TI  - Psoriasis vulgaris does not adversely influence the quality of sleep.
AB  - AIM: Sleep could be severely affected in psoriasis because of skin symptoms and
      psychological repercussions of the disease. The aim of this study was to
      investigate the influence of psoriasis on sleep. METHODS: A total of 202 patients
      with psoriasis and 202 healthy volunteers have completed a self-rated
      questionnaire, the Pittsburgh Sleep Quality Index, which assesses sleep quality
      and disturbances over a 1-month time interval. The severity of the dermatoses has
      been evaluated utilizing the PASI score. RESULTS: In psoriatic patients the
      Pittsburgh Sleep Quality Index resulted between 0 and 17 (5.56+/-3.93), in the
      controls between 0 and 18 (5.13+/-4.16). No statistically significant correlation
      was observed between the score of Pittsburgh Sleep Quality Index and PASI. The
      anti-psoriatic therapy, while causing a marked improvement of lesions and
      itching, does not affect the quality of sleep. CONCLUSION: Although literature
      indicated that psoriasis negatively affects the quality of sleep, in this study
      this correlation was not observed.

PMID- 24442048
TI  - Efficacy of food supplement to improve metabolic syndrome parameters in patients
      affected by moderate to severe psoriasis during anti-TNFalpha treatment.
AB  - AIM: Psoriasis is a systemic inflammatory immune-mediated skin disease. Recently
      a relationship with metabolic syndrome in terms of psoriasis severity and
      response to therapy was observed. METHODS: We performed an open-label randomized
      controlled study to evaluate the role of a nutraceutical containing Q10 coenzyme,
      Krill-oil, lipoic acid, resveratrol, Vitis vinifera seed oil, vitamin E and
      selenium in addition to etanercept therapy for patients affected by psoriasis and
      metabolic syndrome. Forty patients were enrolled and divided into two arms, one
      receiving only etanercept, one other receiving also the neutraceutical. After a
      period of 3 months (T1) a second evaluation of the considered parameters was
      performed. RESULTS: At T1 statistically significant differences were detected in
      HDL cholesterol and triglycerides values both comparing the two arms and in the
      nutraceutical arm. CONCLUSION: Our results show that the dietary addiction of the
      nutraceutical to the etanercept therapy in patients affected by both psoriasis
      and metabolic syndrome could help to restore the normal lipid profile.

PMID- 24442049
TI  - Melanoma in patients younger than 20 years.
AB  - AIM: Melanoma is rare in children and uncommon in adolescents. Clinical and
      prognostic factors can differ from adult population. There is often a delay in
      diagnosis and the therapeutic management is not unequivocally established. The
      aim of this study was to review our monocentric case series to establish the
      characteristics of the population and the possible different behaviour of the
      malignancy compared to adults. METHODS: From 1975 to 2011 we selected 36 out of
      43 patients with a diagnosis of melanoma before the age of 20. We reported a
      female predominance, the most common site of primary lesions for both sexes were
      the lower extremities and according to adulthood population the most common
      histotype was Superficial Spreading Melanoma. RESULTS: None of our patients
      presented distant metastasis at diagnosis, but 29.4% showed a progression, and
      the 17.6% died during the follow-up. A significant difference based on gender was
      found at the multivariate analysis on Disease free survival as well as Breslow
      thickness, but only Breslow thickness was the only parameter that maintained a
      role on survival at multivariate analysis when corrected for gender and age. We
      performed the sentinel lymph node biopsy in 3 patients and they all resulted
      negative. CONCLUSION: Despite our small case series we observed some important
      differences of melanoma in children compared to adults. It remains difficult to
      establish the prognostic factors in younger melanoma patients. Similar to adults,
      the detection of melanoma in an early phase of development, with a low Breslow
      thickness, is the most important prognostic factor.

PMID- 24442050
TI  - Lichen sclerosus and the risk of malignant progression: a case series of 159
      patients.
AB  - AIM AND METHODS: We analyzed 159 stored specimens of Lichen Sclerosus (LS)
      collected in the period 1999-2011 from 159 patients, in order to evaluate the
      histological patterns, clinical outcomes and possible associations with
      malignancies. The histopathologic analysis revealed 145 cases (males and females)
      with LS alone, 7 in whom penile LS was associated with spinocellular carcinoma
      (SCC), and 7 in whom LS was associated with a pseudocarcinomatous-hyperplasia
      (PCH). Extragenital LS was found in 20% (17/85) of the males and 78% (58/74) of
      the females. In the cases of SCC, immunohistochemical analyses was performed.
      RESULTS AND CONCLUSION: The results showed very low positivity to p16INK4A and Ki
      67; biomolecular PCR was positive in only two cases, and in both cases the non
      oncogenic genotype HPV 100 was detected. No important additional risk factors for
      malignancies were found (e.g., hormones, infections, other autoimmune diseases).

PMID- 24442051
TI  - The topical vehicle as a key factor in the management of the psoriatic patients'
      therapy.
AB  - This review deals with the importance of the topical vehicle as a key factor in
      the management of the psoriatic patients' therapy. 

PMID- 24442052
TI  - Jojoba in dermatology: a succinct review.
AB  - Phytomedicine has been successfully used in dermatology horizon for thousands of
      years. Jojoba (Simmondsia chinensis) is a long-lived, drought resistant,
      perennial plant with interesting economic value as it is processed for liquid wax
      production. The jojoba plant produces esters of long-chain alcohols and fatty
      acids (waxes) as a seed lipid energy reserve. The liquid wax is an important
      substrate for a variety of industrial applications and is used in skin treatment
      preparations. The oil from the jojoba plant is the main biological source of wax
      esters and has a multitude of potential applications. The review of literatures
      suggest that jojoba has anti-inflammatory effect and it can be used on a variety
      of skin conditions including skin infections, skin aging, as well as wound
      healing. Moreover, jojoba has been shown to play a role in cosmetics formulas
      such as sunscreens and moisturizers and also enhances the absorption of topical
      drugs. The intention of the review is to summarize the data regarding the uses of
      jojoba in dermatology for readers and researchers.

PMID- 24442053
TI  - Efficacy of a photolyase-based device in the treatment of cancerization field in
      patients with actinic keratosis and non-melanoma skin cancer.
AB  - Eryfotona AK-NMSC (ISDIN Spain) is a film-forming medical device in cream or
      fluid formulation containing the DNA-repair enzyme photolyase and high-protection
      UV filters in liposomes (repairsomes) indicated in the treatment of cancerization
      field in patients with actinic keratosis (AK) or non-melanoma skin cancer (NMSC).
      Photolyase is an enzyme that recognizes and directly repairs UV-induced DNA
      damage. The most common UV-induced DNA damage is the formation of cyclobutane
      pyrimidine dimers (CPD). Clinical studies evaluating the histological and
      cellular effects of Eryfotona AK-NMSC have shown a potential benefit in the
      treatment of the cancerization field in AK patients. In particular the use of
      Eryfotona AK-NMSC improves the confocal microscopic appearance of skin at the
      cancerization field level. In addition, Eryfotona AK-NMSC improves the p53 gene
      expression at keratinocyte level. In this study we reported a series of 6 cases
      of patients with AK or NMSC lesions treated with Eryfotona AK-NMSC fluid, both as
      coadjuvant and as single treatment, applied twice daily in the affected area with
      photograph documentation. Clinical photographs of the skin lesions at baseline
      and after Eryfotona AK-NMSC treatment were taken in all cases using a high
      definition digital camera. Six patients with multiple AK lesions of the scalp or
      face with or without NMSC were treated for a mean of 1-3 months with Eryfotona AK
      NMSC fluid formulation. Image documentations before and after treatment of this
      clinical series show a great improvement in AK lesions count and of cancerization
      field. This clinical series supports the clinical efficacy of the use of
      photolyase and high-protection UV filters in the treatment of cancerization field
      and AK lesions in patients with actinic damage.

PMID- 24442054
TI  - Transient symptomatic zinc deficiency resembling acrodermatitis enteropathica in
      a breast-fed premature infant: case report and brief review of the literature.
AB  - Transient symptomatic zinc deficiency is a rare disorder clinically
      indistinguishable from acrodermatitis enteropathica characterized by
      periorificial and acral dermatitis that usually occurs in exclusively breast-fed
      infant especially if preterm. We describe a three-month-old breast-fed preterm
      boy who developed the typical skin lesions. Maternal breast milk zinc was lower
      than the levels from other 2 mothers of infants at the same gestational age. The
      disease improved and serum zinc level became normal with oral supplementation of
      zinc. No recurrence of the dermatosis was observed when the treatment was stopped
      after weaning. 

PMID- 24442056
TI  - Treatment of pilonidal sinus disease with autologous platelet-rich plasma.

PMID- 24442055
TI  - Juvenile ulcerated necrobiosis lipoidica successfully treated with oral
      cyclosporin A.

PMID- 24442057
TI  - Segmental neurofibromatosis type 1: a frequently underestimated disease.

PMID- 24442058
TI  - Chronic keratosis lichenoides: rare and elusive.

PMID- 24442059
TI  - A case report of fibrosing alopecia in a female pattern distribution.

PMID- 24442060
TI  - [Long term programs in breeding research].
AB  - Plant breeding research on agricultural crops in the Netherlands is described. A
      generally high level of breeding can be expected, when there is close cooperation
      between free research in a university department, directed research in an
      institute (based on a program planned to produce practical results), and private
      plant breeders. The increasing activities and efficiency of private breeders call
      for more basic research and more help on a higher level. Therefore long term
      programs of the Foundation for Agricultural Plant Breeding (S.V.P.) are necessary
      to point out to all interested groups in which direction research may be expected
      to go in the coming period. For long term programs private breeders know in which
      parts of their work the S.V.P. is supposed to help them.The board and heads of
      the institute will have formed a better overall picture of the situation so that
      priority of the different problems can be estimated and flexibility in research
      work can be maintained. It is necessary that the research institute and private
      breeders continually be in contact to avoid misunderstanding, duplication and
      unwanted gaps. To realize this the research workers from the institute should
      regularly visit private breeders and vice versa.Furthermore working groups in
      each of the crops with which S.V.P. is working should meet at least once a year
      to exchange ideas and discuss the actual situation. The S.V.P. itself should not
      breed varieties but should leave this entirely to private breeders. In the
      Netherlands this system has proved to be very workable and satisfactory.The main
      tasks of this research work are: (1) Research in collections. - (2) Detection of
      important characters and their genetical analyses. - (3) Introduction of new
      characters. - (4) Building up parental lines for the benefit of private breeders.
      - (5) Research on breeding methods. - (6) Research on testing methods. - (7)
      Studies on the influence of environmental conditions.Consequently the type of
      specialized research workers has to be changed from "crop experts" to "problem
      solvers". The plant material resulting from their research serves as a building
      stone in the program of the private breeders.The increasing number of specialized
      problems makes it impossible to do all the necessary fundamental research at a
      plant breeding institute. Cooperation with other institutes, specialized in the
      discipline involved, is very important. To maintain a high level of research
      activities it is suggested that strong cooperation between institutes in
      different countries should be aimed at. 

PMID- 24442061
TI  - [South America's genetic reserves for the breeding of cultivated plants].
AB  - The genetic reserves of South America, a continent that has contributed more than
      100 crop plants to the world, are by no means exhausted. On the contrary; among
      the native wild varieties are many potentially useful plants whose improvement
      through breeding is worth undertaking. Among the Solanaceae are especiallyS.
      muricatum, S. topiro, andS. quitoense, furthermoreCyphomandra betacea and certain
      species ofPhysalis, some of which are being subjected to mutation experiments,
      hybridization and selection in order to create new crop varieties for tropical
      latitudes (including the "cool tropical mountains"). Contrary to other Solanaceae
      like tomato and potato (not discussed in this paper) they are immune to viruses
      and other pathogens. The ancient Andean grains from populations ofAmaranthaceae
      andChenopodiaceae with their hundreds of different "landrassen" and types are in
      danger of losing their wealth of genes, because grain import to the Andean states
      has greatly decreased the extent of their cultivation. From both families, on
      which no genetic or breeding experiments have yet been undertaken, frost- and
      droughtresistant fodder plants could be developed for marginal areas. Some of the
      numerous South American indigenous rootcrops have already been extended to all
      continents, others, like the umbelliferousArracacia, are hardly known outside of
      their local areas of growth. Among the South AmericanLeguminosae, protein-rich
      green fodder plants can be developed fromPhaseolus candidus andCanavalia
      ensiformis, similarly from some drought-resistant perennialArachis species. Among
      the numerous South American species of lupines are some semi-domesticated ones,
      likeLupinus perennis andLupinus mutabilis, with softshell seeds and non-opening
      pods but with high alkaloid content. Mutation experiments have been initiated
      successfully at Caracas for obtaining nonpoisonous biotypes. There is hope that
      the protein shortage of the South American Andes region can be alleviated by
      "autochthonous sweet lupines", since the sweet lupine strainsL. luteus andL.
      albus developed byV. SENGBUSCH are not suited to the photoperiodic conditions of
      South America. Finally, it must seriously be pointed out that the rich potencies
      of the South American gene pool are quickly decreasing. In some cases the
      extermination of valuable gene carriers is in full course. No more time should
      therefore be lost in carrying out a practical, feasible program to save the gene
      pools of cultivated plants in South America. 

PMID- 24442062
TI  - [Investigations on the stimulation of fruit body formation in aPleurotis from
      Florida].
AB  - Extracts from fruit bodies ofPleurolus orAgaricus promoted fructification
      ofPleurotus mycelium. This was visible in regular primordia formation 7-10 days
      after application of extract to the mycelium and in higher sporophore
      weights.After fractionating the extracts by ultra- and gel-filtration a marked
      stimulation of sporophore weights was detectable only in fractions of lower
      molecular weight. The number of primordia, however, was also increased by
      compounds of high molecular weight, but not by protein alone.With increasing
      dilution of the extracts the weight of fruit bodies decreased more rapidly than
      the number of primordia.40 mg of L-asparagine or equimolar amounts of urea showed
      an effect similar to that of the extract from 1 g fruit body. Suggars gave no
      reaction.Sporophore initiation and fruit body growth are supposed to be two
      different processes inPleurotus as well as inAgaricus bisporus.Methods for
      detecting a hypothetical sporophore inducer and an inhibitor are discussed. 

PMID- 24442063
TI  - [Breeding experiments with "59c", a mushroom strain with new type of fruit body :
      I. Increase of yield].
AB  - 1. The paper deals with the cultivation and breeding of a mushroom strain which
      produces fruit bodies of an entirely new type. The fruit bodies have neither
      stalk, nor cap, nor gills but are in the form of a clump which can weigh up to
      1,8 kg. They possess an excellent aroma and can be sliced and fried like cutlets
      or be used by the soup industry. In addition to this, they do not require picking
      as frequently as the strains with normal fruit bodies. 2. One of the negative
      characteristics of this strain, known as 59c, is its small total yield. The first
      attempts at breeding were mainly concerned with raising the yield because a
      certain yield is essential if a strain is to be commercially viable. 3. By
      continuous propagation using tissue cultures and selection (i. e. propagation
      were made with fruit bodies from tissue-cultures with the best yields), the yield
      was increased from 35% of normal strains in the 1st tissue culture propagation to
      105% in the 4th tissue culture propagation. 4. However, as a rule, the tissue
      cultures decreased in yield and formed fruit bodies similar to those of a
      pooryielding prototype, Type 59b. 5. The decline in yield and the appearance of
      the prototype can be explained by concentration of the hereditary factors of Type
      59b in the mycelium of the 59c type. The first fruit body of the c-type, formed
      spontaneously in a cultivation bed spawned with 59b, was propagated by tissue
      culture and presumably still contained nuclei with hereditary factors of the type
      59b. They propagated themselves in the course of the mycelium growth. 6. Fruit
      bodies which could be classified as between types 59b and 59c produced both 59c
      forms, and 59b forms, as well as intermediate ones after tissue culture
      propagation. It is probable that they received their form by a certain numerical
      proportion of the nuclei with the hereditary factors for 59b and 59c. 7. Attempts
      to maintain the high yield of 59c at a constant level (elimination of the 59b
      nuclei) and to improve the quality of the fruit bodies are initiated. 

PMID- 24442064
TI  - [Development of an early test for anthocyanin formation in asparagus].
AB  - 1. An early test is described which makes it possible to recognize anthocyanin
      containing seedlings of asparagus. The test can be used to separate the progeny
      from anthocyanin-free single plants into types containing anthocyanin and those
      which are free of it. 2. The early test requires only 15 to 18 days in comparison
      with the field test which takes about 400 days. Thus very important information
      for the breeding of asparagus is obtainable 15 months earlier. 3. An agreement
      was found between the field anthocyanin test and the early test. On 3.9 mill.
      selected individuals of the variety 'Spaganiva' which were free of anthocyanin
      types it was demonstrated that the early test gives true results. 

PMID- 24442065
TI  - [The breeding of strawberries suited for freezing : I. Breeding potential and
      ecovalence of two "freezing" characteristics].
AB  - Heritability in the broad sense, the expected genetic advance with selection and
      the repeatabilities for two freezing characteristics were estimated in strawberry
      clones (Fragaria ananassa Duch.) over several years. The freezing characteristics
      were extravasation of juice and texture of berries after thawing. It could be
      shown that after 12-15 years of breeding and selection there was still much
      genetic variance. An estimation of ecovalence for these characteristics showed
      that ecovalence depends on genetic diversity. 

PMID- 24442066
TI  - [Hypophyseal injections for aquarium carp and artificial spawning as a method for
      breeding new races of carp].
AB  - A method of raising and multiplying carp is reported which makes a faster
      establishment of new breeds possible.Carp (Cyprinus carpio) raised in aquaria and
      fed on dry food reached maturity already after two years. Pituitary injections
      make it possible to obtain roe and milt from such fish.Fertilization, hatching,
      and raising of the young are also performed under laboratory conditions.There is
      no endogenous sexual rhythm in carp, for spawning can be accomplished at any time
      of the year, and several times annually using the same parents. The method of
      artificially obtaining and hatching spawn is described. It is suitable for
      breeding and physiological experiments.A comparative analysis of the
      physiological dynamics in eggs, young fish, and adults is considerably simplified
      for the physiologist interested in metabolism, and the breeder can reach his
      goals more rapidly because of the shortened generation time. 

PMID- 24442067
TI  - [On breeding burst-resistant self-pruning tomatoes : Preliminary communication].
AB  - From crossings of a self-pruning German commercial tomato variety with medium
      sized round fruits, relative resistance against bursting in rain with a self
      pruning Central American form with medium sized pruneshaped and never bursting
      fruits a selfpruning F1 was obtained whose round fruits of medium size never
      burst. In the F2 a greater number of self-pruning types with round fruits
      completely burst-resistant and of medium size was found. One self-pruning and
      burst-resistant plant had remarkably large fruits. Furthermore, two dwarfs and a
      great number of "cherry"-tomatoes were found. The value of these findings for
      plant breeding and evolution is discussed. 

PMID- 24442068
TI  - [Investigations on the inheritance of the charactergrandiflora inPetunia*hybrida
      Vilm : II. The use of tetraploidgrandiflora lines for the breeding of
      newsuperbissima forms, especially those with yellow flowers].
AB  - 1. In the diploid petunias of the class ofgrandiflora the dominant alleleG at
      thegrandiflora locus which determines the character of large flowers is normally
      linked to a recessive lethal genel which eliminates zygotes and simultaneously
      diminishes the chance of fertilization of the pollen transferring it. Large
      flowered petunia plants in the class ofgrandiflora are therefore normally
      heterozygous with respect to the alleles of thegrandiflora locus and have the
      genotypeGl/gL. Grandiflora homozygotesGl/GL orGL/GL originate from rare crossover
      events, and so does the genotypeGL/gl. 2. Since the very bright leaf color of
      thegrandiflora homozygotes reduces their vigor, the breeding of homozygous large
      flowered varieties has no practical importance. A special interest therefore
      arises for the genotypeGL/gl because, in spite of heterozygosity, the offspring
      do not include undesirable small-flowered plants with the exception of some
      originating from rare combinations of crossover gametes. 3. The tetraploid
      genotypeGL/GL/gl/gl was produced by colchicine treatment. Analysis of the
      offsprings of the next two generations showed that in tetraploid material the
      zygotic effect of the lethal gene works in the same way as in diploids, producing
      again automatic elimination of small-flowered plants. Moreover, it was found that
      gametes of the genotypegl/gl can be transferred not only by egg-cells but also by
      the pollen. 4. Consequently, it is possible to achieve an automatic elimination
      of the small-flowered plants also in the tetraploid class ofsuperbissima. This
      may be done by replacing the linkage groupgL ofsuperbissima petunias by thegl
      type of the artificially produced new tetraploid material. Homozygous large
      flowered plants do not occur in tetraploid material because gametes of the
      genotypeGG are not transferable by the pollen. 5. Particularly the above
      mentioned qualities, that is the crossability to tetraploid petunias of the class
      ofsuperbissima and the possibility of transferring some desired characters, as
      for example the linkage groupgl or the yellow flower color to the latter,
      determine the value of the newly produced tetraploid material. Since some of the
      typical characters ofSuperbissima petunias, particularly those concerning flower
      shape, do not occur in the new tetraploid material the latter is of no direct
      ornamental interest, except for the yellow-flowered lines. 6. The alleleG which
      produces large flowers both insuperbissima and in the new tetraploid material
      brightens, in addition, the leaf color in the new tetraploid material. Since the
      degree of brightness increases with the number ofG alleles in the genotype, it is
      rather easy to identify the different tetraploid heterozygotes in the new
      material. 7. Yellow-flowered lines were also produced as starting material for
      the polyploidization of the genotypeGL/gl. Tetraploid yellow-flowered lines were
      produced in order to examine whether the tint of the yellow flower color,
      unsatisfactory in large-flowered diploid varieties, could be intensified by
      tetraploidy. Because the yellow flower color did occur insuperbissima, the newly
      produced tetraploid yellow-flowered material is important also for transmission
      of this character to the latter. The experiments showed that the intensity of
      yellow flower color in the new tetraploid yellow-flowered and very large-flowered
      material still does not reach that of modern diploid small-floweredmultiflora
      petunias. However, for the production of both practically pure, large, and yellow
      flowered tetraploid varieties and of tetraploid large and yellow-flowered F1
      hybrids the new material offers interesting possibilities, which are discussed in
      detail. 

PMID- 24442069
TI  - [Complete variances and covariances in plant stands : IV. Phenotypic correlations
      between growth at different ages].
AB  - 1. Multiple correlations of diameters or basal areas of single trees on sums of
      diameters or basal areas of neighbors, weighted by reciprocal quadratic distances
      between tree and neighbor, including both simultaneous measurements and sums of
      neighbors at preceding times resulted in appreciably higher r(2) than those based
      on simultaneous measurements only. 2. Selection of trees with largest diameters
      at an age of 30-50 years compared with selection at older ages resulted in
      relatively small losses in selection differential. 

PMID- 24442070
TI  - Design of multifunctional alkali ion doped CaF2 upconversion nanoparticles for
      simultaneous bioimaging and therapy.
AB  - Herein, alkali ion doped CaF2 upconversion nanoparticles (UCNPs) were first
      reported as a multifunctional theranostic platform for dual-modal imaging and
      chemotherapy. Interestingly, we found that the alkali ions doping approach could
      efficiently enhance the upconversion luminescence (UCL) intensity, whereas
      slightly affect the phase and morphology of the resulting products. In order to
      further improve the UCL efficacy for bioimaging, a pristine CaF2 shell was grown
      on the CaF2:Yb, Er core surface to enhance the UCL intensity. After being
      transferred into hydrophilic UCNPs, these water-soluble UCNPs could be served as
      contrast agents for in vitro/in vivo UCL imaging and X-ray computed tomography
      (CT) imaging. Furthermore, the as-prepared UCNPs could also be employed as nano
      carriers for drug delivery. Doxorubicin (DOX) can be easily loaded onto the UCNPs
      and the DOX-loaded UCNPs exhibit a good cell killing ability. Therefore, the
      multifunctional core-shell CaF2 UCNPs with UCL/CT imaging and drug carrier
      properties may find extensive applications in simultaneous imaging diagnosis and
      therapy. 

PMID- 24442072
TI  - The impact of aerators on water contamination by emerging gram-negative
      opportunists in at-risk hospital departments.
AB  - OBJECTIVE: Our aim was to evaluate the impact of aerators on water
      microbiological contamination in at-risk hospital departments, with a view to
      quantifying the possible risk of patient exposure to waterborne microorganisms.
      DESIGN: We analyzed the microbiological and chemical-physical characteristics of
      hot and cold water in some critical hospital departments. SETTING: Two hospitals
      in northern Italy. METHODS: We took 304 water samples over a 1-year period, at 3
      month intervals, from taps used by healthcare personnel for handwashing, surgical
      washing, and the washing of medical equipment. We analyzed heterotrophic plate
      counts (HPCs) at 36 degrees C and 22 degrees C, nonfastidious gram-negative
      bacteria (GNB-NE), and Legionella pneumophila. RESULTS: The percentages of
      positivity and mean values of HPCs at 22 degrees C, HPCs at 36 degrees C, and GNB
      NE loads were significantly higher at outlet points than in the plumbing system.
      In particular, GNB-NE positivity was higher at outlet points than in the plumbing
      system in both the cold water (31.58% vs 6.58% of samples were positive) and hot
      water (21.05% vs 3.95%) supplies. Our results also revealed contamination by L.
      pneumophila both in the plumbing system and at outlet points, with percentages of
      positive samples varying according to the serogroup examined (serogroups 1 and 2
      14). The mean concentrations displayed statistically significant (P < .001)
      differences between the outlet points (27,382.89 +/- 42,245.33 colony-forming
      units [cfu]/L) and the plumbing system (19,461.84 +/- 29,982.11 cfu/L).
      CONCLUSIONS: These results reveal a high level of contamination of aerators by
      various species of gram-negative opportunists that are potentially very dangerous
      for immunocompromised patients and, therefore, the need to improve the management
      of these devices.

PMID- 24442071
TI  - Healthcare personnel attire in non-operating-room settings.
AB  - Healthcare personnel (HCP) attire is an aspect of the medical profession steeped
      in culture and tradition. The role of attire in cross-transmission remains poorly
      established, and until more definitive information exists priority should be
      placed on evidence-based measures to prevent healthcare-associated infections
      (HAIs). This article aims to provide general guidance to the medical community
      regarding HCP attire outside the operating room. In addition to the initial
      guidance statement, the article has 3 major components: (1) a review and
      interpretation of the medical literature regarding (a) perceptions of HCP attire
      (from both HCP and patients) and (b) evidence for contamination of attire and its
      potential contribution to cross-transmission; (2) a review of hospital policies
      related to HCP attire, as submitted by members of the Society for Healthcare
      Epidemiology of America (SHEA) Guidelines Committee; and (3) a survey of SHEA and
      SHEA Research Network members that assessed both institutional HCP attire
      policies and perceptions of HCP attire in the cross-transmission of pathogens.
      Recommendations for HCP attire should attempt to balance professional appearance,
      comfort, and practicality with the potential role of apparel in the cross
      transmission of pathogens. Although the optimal choice of HCP attire for
      inpatient care remains undefined, we provide recommendations on the use of white
      coats, neckties, footwear, the bare-below-the-elbows strategy, and laundering.
      Institutions considering these optional measures should introduce them with a
      well-organized communication and education effort directed at both HCP and
      patients. Appropriately designed studies are needed to better define the
      relationship between HCP attire and HAIs. 

PMID- 24442073
TI  - Waterborne pathogen detection: more than just "location, location, location...".

PMID- 24442074
TI  - Automated alerts coupled with antimicrobial stewardship intervention lead to
      decreases in length of stay in patients with gram-negative bacteremia.
AB  - OBJECTIVE: To assess the impact of active alerting of positive blood culture data
      coupled with stewardship intervention on time to appropriate therapy, length of
      stay, and mortality in patients with gram-negative bacteremia. DESIGN: Quasi
      experimental retrospective cohort study in patients with gram-negative bacteremia
      at the Detroit Medical Center from 2009 to 2011. SETTING: Three hospitals (1
      community, 2 academic) with active antimicrobial stewardship programs within the
      Detroit Medical Center. PATIENTS: All patients with monomicrobial gram-negative
      bacteremia during the study period. INTERVENTION: Active alerting of positive
      blood culture data coupled with stewardship intervention (2010-2011) compared
      with patients who received no formalized stewardship intervention (2009).
      RESULTS: Active alerting and intervention led to a decreased time to appropriate
      therapy (8 [interquartile range (IQR), 2-24] vs 14 [IQR, 2-35] hours; P = .014)
      in patients with gram-negative bacteremia. After controlling for differences
      between groups, being in the intervention arm was associated with an independent
      reduction in length of stay (odds ratio [OR], 0.73 [95% confidence interval (CI),
      0.62-0.86]), correlating to a median attributable decrease in length of stay of
      2.2 days. Additionally, multivariate modeling of patients who were not on
      appropriate antimicrobial therapy at the time of initial culture positivity
      showed that patients in the intervention group had a significant reduction in
      both length of stay (OR, 0.76 [95% CI, 0.66-0.86]) and infection-related
      mortality (OR, 0.24 [95% CI, 0.08-0.76]). CONCLUSIONS: Active alerting coupled
      with stewardship intervention in patients with gram-negative bacteremia
      positively impacted time to appropriate therapy, length of stay, and mortality
      and should be a target of antimicrobial stewardship programs.

PMID- 24442076
TI  - Impact of Medicare's payment policy on mediastinitis following coronary artery
      bypass graft surgery in US hospitals.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented a
      policy in October 2008 to eliminate additional Medicare payment for mediastinitis
      following coronary artery bypass graft (CABG) surgery. OBJECTIVE: To evaluate the
      impact of this policy on mediastinitis rates, using Medicare claims and National
      Healthcare Safety Network (NHSN) prospective surveillance data. METHODS: We used
      an interrupted time series design to compare mediastinitis rates before and after
      the policy, adjusted for secular trends. Billing rates came from Medicare
      inpatient claims following 638,761 CABG procedures in 1,234 US hospitals (January
      2006-September 2010). Prospective surveillance rates came from 151 NHSN hospitals
      in 29 states performing 94,739 CABG procedures (January 2007-September 2010).
      Logistic regression mixed-effects models estimated trends for mediastinitis
      rates. RESULTS: We found a sudden drop in coding for index admission
      mediastinitis at the time of policy implementation (odds ratio, 0.36 [95%
      confidence interval (CI), 0.23-0.57]) and a decreasing trend in coding for index
      admission mediastinitis in the postintervention period compared with the
      preintervention period (ratio of slopes, 0.83 [95% CI, 0.74-0.95]). However, we
      saw no impact of the policy on infection rates as measured using NHSN data. Our
      results were not affected by changes in patient risk over time, heterogeneity in
      hospital demographics, or timing of hospital participation in NHSN. CONCLUSIONS:
      The CMS policy of withholding additional Medicare payment for mediastinitis on
      the basis of claims-based evidence of infection was associated with changes in
      coding for infections but not with changes in actual infection rates during the
      first 2 years after policy implementation.

PMID- 24442075
TI  - Pseudo-outbreak of Klebsiella oxytoca spontaneous bacterial peritonitis
      attributed to contamination of multidose vials of culture medium supplement.
AB  - OBJECTIVE: To determine the source of a cluster of Klebsiella oxytoca isolates
      cultured from peritoneal fluid of 3 patients with cirrhosis on a single day.
      DESIGN: Outbreak investigation and before-after study. SETTING: A Veterans
      Affairs medical center. METHODS: Epidemiologic investigation, analysis of
      antimicrobial susceptibility testing results and molecular typing of K. oxytoca
      isolates with repetitive sequence-based polymerase chain reaction (rep-PCR),
      review of microbiology laboratory procedures for processing peritoneal fluid
      cultures, and comparison of peritoneal fluid contamination rates 18 months before
      and after modification of laboratory procedures for culturing peritoneal fluid.
      RESULTS: Each of the peritoneal fluid samples that grew K. oxytoca was inoculated
      into blood culture bottles by different clinicians at different hospital
      locations. None of the patients had clinical findings suggestive of peritonitis
      or elevated polymorphonuclear cell counts in peritoneal fluid (range, 3-25
      cells/MUL). Molecular typing with rep-PCR demonstrated that the K. oxytoca
      isolates were genetically related (greater than 95% similarity). Laboratory
      procedures included the routine addition of a culture medium supplement of yeast
      extract and dextrose from a multidose vial into blood culture bottles with
      peritoneal fluid. After discontinuing use of the culture medium supplement, there
      was a marked reduction in the number of peritoneal fluid cultures deemed as
      contaminants (14.3% vs 0.9%; [Formula: see text]). CONCLUSION: A pseudo-outbreak
      of K. oxytoca peritonitis and high rates of contamination of peritoneal fluid
      were attributable to contamination of a multidose culture medium supplement. This
      article highlights the importance of discouraging the use of multidose vials in
      all clinical settings.

PMID- 24442077
TI  - Readmissions after diagnosis of surgical site infection following knee and hip
      arthroplasty.
AB  - CONTEXT: Surgical site infection (SSI) after total hip and knee arthroplasty is a
      common postoperative complication. We sought to determine readmission rates and
      costs for total hip and knee arthroplasty complicated by SSI. DESIGN: The Thomson
      Reuters MarketScan database was searched for patients who underwent knee or hip
      arthroplasty in 2007. From these data, patients who received a diagnosis of SSI
      and were readmitted after diagnosis were identified. SETTING: A population of 31
      to 45 million individuals receiving insurance coverage. Patients who underwent
      knee or hip arthroplasty who experienced a hospitalization for SSI in the year
      after surgery were analyzed. OUTCOME MEASURES: Total readmission rates and costs
      per readmission at 30, 60, and 90 days and 1 year after diagnosis of SSI.
      RESULTS: Of the 76,289 case patients with hip or knee replacement in 2007, 1,026
      (1.3%) had a hospitalization for SSI within the year after surgery. Among these
      patients, 310 (30.2%) were subsequently rehospitalized in the year after initial
      hospitalization specifically due to SSI-related issues. These rehospitalizations
      were associated with a mean hospital stay of [Formula: see text] days and a
      median cost of $20,001 (interquartile range [IQR], $14,057-$30,551). A total of
      517 subjects had a subsequent "all-cause" hospitalization during the year after
      SSI. These rehospitalizations were associated with a mean hospital stay of
      [Formula: see text] days and a median cost of $19,870 (IQR, $13,913-$29,728).
      CONCLUSIONS: Readmissions during the year after SSI diagnosis accounted for 1,072
      hospital admissions and cost over $25.5 million. These readmissions are costly
      and might be a future target for decreased reimbursement.

PMID- 24442078
TI  - Chlorhexidine bathing in a tertiary care neonatal intensive care unit: impact on
      central line-associated bloodstream infections.
AB  - BACKGROUND: Despite implementation of recommended best practices, our central
      line-associated bloodstream infection (CLABSI) rates remained high. Our objective
      was to describe the impact of chlorhexidine gluconate (CHG) bathing on CLABSI
      rates in neonates. METHODS: Infants with a central venous catheter (CVC) admitted
      to the neonatal intensive care unit from April 2009 to March 2013 were included.
      Neonates with a birth weight of 1,000 g or less, aged less than 28 days, and
      those with a birth weight greater than 1,000 g were bathed with mild soap until
      March 31, 2012 (baseline), and with a 2% CHG-impregnated cloth starting on April
      1, 2012 (intervention). Infants with a birth weight of 1,000 g or less, aged 28
      days or more, were bathed with mild soap during the entire period. Neonatal
      intensive care unit nurses reported adverse events. Adjusted incidence rate
      ratios (aIRRs), using Poisson regression, were calculated to compare
      CLABSIs/1,000 CVC-days during the baseline and intervention periods. RESULTS:
      Overall, 790 neonates with CVCs were included in the study. CLABSI rates
      decreased during the intervention period for CHG-bathed neonates (6.00 vs
      1.92/1,000 CVC-days; aIRR, 0.33 [95% confidence interval (CI), 0.15-0.73]) but
      remained unchanged for neonates with a birth rate of 1,000 g or less and aged
      less than 28 days who were not eligible for CHG bathing (8.57 vs 8.62/1,000 CVC
      days; aIRR, 0.86 [95% CI, 0.17-4.44]). Overall, 195 infants with a birth weight
      greater than 1,000 g and 24 infants with a birth weight of 1,000 g or less, aged
      28 days or more, were bathed with CHG. There was no reported adverse event.
      CONCLUSIONS: We observed a decrease in CLABSI rates in CHG-bathed neonates in the
      absence of observed adverse events. CHG bathing should be considered if CLABSI
      rates remain high, despite the implementation of other recommended measures.

PMID- 24442079
TI  - The descriptive epidemiology of central line-associated bloodstream infection
      among patients in non-intensive care unit settings.
AB  - OBJECTIVE: To review and describe device utilization and central line-associated
      bloodstream (CLABSI) events among patients in a non-intensive care unit (ICU)
      setting and to examine the morbidity and mortality associated with these events.
      DESIGN: One-year descriptive review. SETTING: A single tertiary center with a
      1,200-bed hospital and 209 adult ICU beds. PATIENTS: Hospitalized patients
      identified as having a CLABSI event attributed to a non-ICU setting. METHODS: The
      cohort was identified from a prospective infection prevention database. Charts
      and administrative data sets were reviewed to further characterize the patients.
      Device utilization ratios (DURs) and CLABSI rates were calculated using National
      Health and Safety Network (NHSN) CLABSI definitions. Need for ICU stay and crude
      mortality rates were recorded. RESULTS: A total of 136 patients with 156 CLABSIs
      were identified, of whom 78 (57%) were being treated for a hematological
      malignancy (HM). The overall DUR was 0.27. A tunneled line was in place for 118
      (76%) of the CLABSI events, and a peripherally inserted central catheter was in
      place for 32 (21%) of the CLABSI events. The non-ICU CLABSI rate was
      significantly higher than the concurrent ICU rate (2.1 CLABSIs per 1,000 catheter
      days vs 1.5 CLABSIs per 1,000 catheter-days; [Formula: see text]). Hospital
      mortality was 23% in the affected group and was significantly higher in patients
      with HM. CONCLUSIONS: CLABSI rates over a 1-year period were higher in patients
      outside the ICU at our hospital and were associated with significant mortality.

PMID- 24442081
TI  - Compliance with postexposure screening and treatment of latent tuberculosis
      infection among healthcare workers in a tertiary care hospital in Saudi Arabia.
AB  - BACKGROUND: Controlling tuberculosis (TB) infection among occupationally exposed
      healthcare workers (HCWs) may be challenging. METHODS: We retrospectively
      reviewed clinical records of HCWs who were exposed to patients diagnosed with
      infectious TB at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 2008
      and 2010. The collected data included baseline tuberculin skin test (TST) status,
      potential predictors of TST positivity, postexposure diagnosis of latent TB
      infection (LTBI), and postexposure compliance with LTBI therapy. RESULTS:
      Thirteen patients were diagnosed with infectious pulmonary TB during the study
      period. A total of 298 HCWs met our definition for exposure. Exposed HCWs tended
      to be female (62.9%), non-Saudi (83.9%), nurses (68.6%), or respiratory
      therapists (24.0%) working in critical care locations (72.8%). Baseline
      (preemployment) TST documentation existed for 41.3% (123/298). Among those with
      documented baseline TSTs, 51.2% (63/123) were positive, representing 21.1%
      (63/298) of all HCWs. Only 48.9% (115/235) of exposed HCWs who had negative or
      unknown preexposure TST status had their TST tested after exposure. Approximately
      46.1% (53/115) of them were diagnosed with postexposure LTBI, and 92.5% (49/53)
      of them were prescribed LTBI therapy. Among those, 93.9% (46/49) started LTBI
      therapy; however, 82.6% (38/46) failed to complete the recommended course.
      CONCLUSIONS: We found low rates of baseline TST documentation and postexposure
      screening among exposed HCWs. Compliance with initiating postexposure isoniazid
      prophylaxis among HCWs was fair, but only a small fraction of those who started
      prophylaxis completed the recommended course of therapy. These findings suggest
      substantial opportunities to implement administrative measures to enhance LTBI
      management among HCWs.

PMID- 24442080
TI  - Healthcare-associated influenza in Canadian hospitals from 2006 to 2012.
AB  - OBJECTIVE: To determine trends, patient characteristics, and outcome of patients
      with healthcare-associated influenza in Canadian hospitals. DESIGN: Prospective
      surveillance of laboratory-confirmed influenza among hospitalized adults was
      conducted from 2006 to 2012. Adults with positive test results at or after
      admission to the hospital were assessed. Influenza was considered to be
      healthcare associated if symptom onset was equal to or more than 96 hours after
      admission to a facility or if a patient was readmitted less than 96 hours after
      discharge or admitted less than 96 hours after transfer from another facility.
      Baseline characteristics of influenza patients were collected. Patients were
      reassessed at 30 days to determine the outcome. SETTING: Acute care hospitals
      participating in the Canadian Nosocomial Infection Surveillance Program. RESULTS:
      A total of 570 (17.3%) of 3,299 influenza cases were healthcare associated; 345
      (60.5%) were acquired in a long-term care facility (LTCF), and 225 (39.5%) were
      acquired in an acute care facility (ACF). There was year-to-year variability in
      the rate and proportion of cases that were healthcare associated and variability
      in the proportion that were acquired in a LTCF versus an ACF. Patients with LTCF
      associated cases were older, had a higher proportion of chronic heart disease,
      and were less likely to be immunocompromised compared with patients with ACF
      associated cases; there was no significant difference in 30-day all-cause and
      influenza-specific mortality. CONCLUSIONS: Healthcare-associated influenza is a
      major component of the burden of disease from influenza in hospitals, but the
      proportion of cases that are healthcare associated varies markedly from year to
      year, as does the proportion of healthcare-associated infections that are
      acquired in an ACF versus an LTCF.

PMID- 24442082
TI  - Prevalence of rectal colonization with multidrug-resistant Enterobacteriaceae
      among international patients hospitalized at Mayo Clinic, Rochester, Minnesota.
AB  - Rectal colonization with multidrug-resistant Enterobacteriaceae was found in 23
      of 94 consecutively enrolled international patients hospitalized at Mayo Clinic,
      Rochester, Minnesota. No carbapenemase producers were detected. Twenty-one
      isolates were extended-spectrum beta-lactamase-producing Escherichia coli.
      Colonization was associated with gastrointestinal disease and central venous
      catheter placement within the antecedent year. 

PMID- 24442083
TI  - A cluster of methicillin-susceptible Staphylococcus aureus infections at a
      rheumatology practice, New York City, 2011.
AB  - A cluster of 5 methicillin-susceptible Staphylococcus aureus infections occurred
      after administration of methylprednisolone acetate injections in a rheumatology
      practice. A site visit was conducted to inspect examination rooms, observe
      techniques, and review charts. The investigation revealed a pervasive lack of
      aseptic technique that led to multiple opportunities for medication
      contamination. 

PMID- 24442084
TI  - Residential proximity to large numbers of swine in feeding operations is
      associated with increased risk of methicillin-resistant Staphylococcus aureus
      colonization at time of hospital admission in rural Iowa veterans.
AB  - Among 1,036 patients, residential proximity within 1 mile of large swine
      facilities was associated with nearly double the risk of methicillin-resistant
      Staphylococcus aureus (MRSA) colonization at admission (relative risk, 1.8786
      [95% confidence interval, 1.0928-3.2289]; P = .0239) and, after controlling for
      multiple admissions and age, was associated with nearly triple the odds of MRSA
      colonization (odds ratio, 2.76 [95% confidence interval, 1.2728-5.9875]; P =
      .0101).

PMID- 24442085
TI  - Evaluation of an antimicrobial stewardship approach to minimize overuse of
      antibiotics in patients with asymptomatic bacteriuria.
AB  - An antimicrobial stewardship educational initiative provided to physicians and
      pharmacists was evaluated at an academic medical center to minimize inappropriate
      treatment of asymptomatic bacteriuria (ASB). A significant decrease in empirical
      antimicrobial use for ASB was observed after education. Multifaceted educational
      initiatives can reduce inappropriate antimicrobial treatment of ASB. 

PMID- 24442086
TI  - Comparison of 3 severity criteria for Clostridium difficile infection.
AB  - Effective severity criteria are needed to guide management of Clostridium
      difficile infection (CDI). In this retrospective study, outcomes were compared
      between patients with mild-moderate versus severe CDI according to 3 different
      severity criteria: those included in the 2010 Society for Healthcare Epidemiology
      of America/Infectious Diseases Society of America guidelines, those from a recent
      clinical trial, and our hospital-specific guidelines. 

PMID- 24442087
TI  - The growing importance of non-device-associated healthcare-associated infections:
      a relative proportion and incidence study at an academic medical center, 2008
      2012.

PMID- 24442089
TI  - A randomized trial of soap and water hand wash versus alcohol hand rub for
      removal of Clostridium difficile spores from hands of patients.

PMID- 24442088
TI  - More cleaning, less screening: evaluation of the time required for monitoring
      versus performing environmental cleaning.

PMID- 24442090
TI  - Infection prevention control bundle of multidrug-resistant Acinetobacter
      baumannii and methicillin-resistant Staphylococcus aureus: which one is more
      important?

PMID- 24442091
TI  - Germ and hematology: underlying disease influences diversity of germ spectra and
      antibiotic therapy.

PMID- 24442094
TI  - Dissociable effects of antipsychotics on ketamine-induced changes in regional
      oxygenation and inter-regional coherence of low frequency oxygen fluctuations in
      the rat.
AB  - Typical and atypical antipsychotics have been shown to alleviate N-methyl-D
      aspartate (NMDA) receptor antagonist-induced BOLD signals in healthy humans and
      animals to differing degrees; factors that might relate to their different
      molecular mechanisms and clinical profiles. Recent studies have also extended
      these investigations to the analysis of resting state functional connectivity
      measures of BOLD signals in different brain regions. Using constant potential
      amperometry, we examined the effects of the NMDA receptor antagonist S-(+)
      ketamine on tissue oxygen levels in medial prefrontal cortex (mPFC) and medial
      ventral striatum (mVS), and temporal coherence of low-frequency oxygen
      fluctuations between these regions in freely moving rats. Furthermore, we
      assessed the extent to which the atypical antipsychotic clozapine and the typical
      antipsychotic haloperidol could modulate the effects of S-(+)-ketamine on these
      measures. Acute S-(+)-ketamine (5-25 mg/kg) produced dose-dependent increases in
      both tissue O2 levels and coherence. Although effects of clozapine and
      haloperidol alone were relatively minor, their effects on ketamine-induced
      signals were markedly more distinct. Clozapine dose-dependently attenuated the
      absolute S-(+)-ketamine (25 mg/kg) O2 signal in both regions, and also attenuated
      ketamine-induced increases in regional coherence. Haloperidol had no effect on
      the absolute ketamine O2 signal yet potentiated increases in regional coherence.
      The dissociable effects of haloperidol and clozapine on ketamine-induced
      hyperoxygenation and mPFC-mVS coherence elucidate potentially important
      mechanistic differences between these classes of pharmacology. This study
      demonstrates for the first time that in vivo amperometry can measure both
      regional brain tissue O2 levels and inter-regional coherence, advancing BOLD-like
      measurements of functional connectivity into awake, unconstrained animals.

PMID- 24442095
TI  - Dopamine in the dorsal hippocampus impairs the late consolidation of cocaine
      associated memory.
AB  - Cocaine is thought to be addictive because it elevates dopamine levels in the
      striatum, reinforcing drug-seeking habits. Cocaine also elevates dopamine levels
      in the hippocampus, a structure involved in contextual conditioning as well as in
      reward function. Hippocampal dopamine promotes the late phase of consolidation of
      an aversive step-down avoidance memory. Here, we examined the role of hippocampal
      dopamine function in the persistence of the conditioned increase in preference
      for a cocaine-associated compartment. Blocking dorsal hippocampal D1-type
      receptors (D1Rs) but not D2-type receptors (D2Rs) 12 h after a single training
      trial extended persistence of the normally short-lived memory; conversely, a
      general and a specific phospholipase C-coupled D1R agonist (but not a D2R or
      adenylyl cyclase-coupled D1R agonist) decreased the persistence of the normally
      long-lived memory established by three-trial training. These effects of D1 agents
      were opposite to those previously established in a step-down avoidance task, and
      were here also found to be opposite to those in a lithium chloride-conditioned
      avoidance task. After returning to normal following cocaine injection, dopamine
      levels in the dorsal hippocampus were found elevated again at the time when
      dopamine antagonists and agonists were effective: between 13 and 17 h after
      cocaine injection. These findings confirm that, long after the making of a
      cocaine-place association, hippocampal activity modulates memory consolidation
      for that association via a dopamine-dependent mechanism. They suggest a dynamic
      role for dorsal hippocampal dopamine in this late-phase memory consolidation and,
      unexpectedly, differential roles for late consolidation of memories for places
      that induce approach or withdrawal because of a drug association.

PMID- 24442097
TI  - Inflammatory and metabolic dysregulation and the 2-year course of depressive
      disorders in antidepressant users.
AB  - Scarce evidence suggests that inflammatory and metabolic dysregulation predicts
      poor response to antidepressants, which could result in worse depression outcome.
      This study prospectively examined whether inflammatory and metabolic
      dysregulation predicted the 2-year course of depressive disorders among
      antidepressant users. Data were from the Netherlands Study of Depression and
      Anxiety, including 315 persons (18-65 years) with a current depressive disorder
      (major depressive disorder, dysthymia) at baseline according to the DSM-IV
      criteria and using antidepressants. Inflammatory (C-reactive protein, interleukin
      6 (IL-6), tumor-necrosis factor-alpha) and metabolic (waist circumference,
      triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure,
      fasting glucose) factors were measured at baseline. Primary outcome for course of
      depression was indicated by whether or not a DSM-IV depressive disorder diagnosis
      was still/again present at 2-year follow-up, indicating chronicity of depression.
      Elevated IL-6, low HDL cholesterol, hypertriglyceridemia, and hyperglycemia were
      associated with chronicity of depression in antidepressant users. Persons showing
      ? 4 inflammatory or metabolic dysregulations had a 1.90 increased odds of
      depression chronicity (95% CI = 1.12-3.23). Among persons who recently (ie, at
      most 3 months) started antidepressant medication (N = 103), having ? 4
      dysregulations was associated with a 6.85 increased odds of depression chronicity
      (95% CI = 1.95-24.06). In conclusion, inflammatory and metabolic dysregulations
      were found to predict a more chronic course of depressive disorders among
      patients using antidepressants. This could suggest that inflammatory and
      metabolic dysregulation worsens depression course owing to reduced antidepressant
      treatment response and that alternative intervention treatments may be needed for
      depressed persons with inflammatory and metabolic dysregulation.

PMID- 24442096
TI  - Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine
      receptor positive allosteric modulator VU0152100.
AB  - Accumulating evidence suggests that selective M4 muscarinic acetylcholine
      receptor (mAChR) activators may offer a novel strategy for the treatment of
      psychosis. However, previous efforts to develop selective M4 activators were
      unsuccessful because of the lack of M4 mAChR subtype specificity and off-target
      muscarinic adverse effects. We recently developed VU0152100, a highly selective
      M4 positive allosteric modulator (PAM) that exerts central effects after systemic
      administration. We now report that VU0152100 dose-dependently reverses
      amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M4 KO
      mice. VU0152100 also blocks amphetamine-induced disruption of the acquisition of
      contextual fear conditioning and prepulse inhibition of the acoustic startle
      reflex. These effects were observed at doses that do not produce catalepsy or
      peripheral adverse effects associated with non-selective mAChR agonists. To
      further understand the effects of selective potentiation of M4 on region-specific
      brain activation, VU0152100 alone and in combination with amphetamine were
      evaluated using pharmacologic magnetic resonance imaging (phMRI). Key neural
      substrates of M4-mediated modulation of the amphetamine response included the
      nucleus accumbens (NAS), caudate-putamen (CP), hippocampus, and medial thalamus.
      Functional connectivity analysis of phMRI data, specifically assessing
      correlations in activation between regions, revealed several brain networks
      involved in the M4 modulation of amphetamine-induced brain activation, including
      the NAS and retrosplenial cortex with motor cortex, hippocampus, and medial
      thalamus. Using in vivo microdialysis, we found that VU0152100 reversed
      amphetamine-induced increases in extracellular dopamine levels in NAS and CP. The
      present data are consistent with an antipsychotic drug-like profile of activity
      for VU0152100. Taken together, these data support the development of selective M4
      PAMs as a new approach to the treatment of psychosis and cognitive impairments
      associated with psychiatric disorders such as schizophrenia. 

PMID- 24442098
TI  - Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic
      tumors rather than as a single agent in advanced non-small cell lung cancer.
AB  - OBJECTIVES: Dichloroacetate (DCA) is a highly bioavailable small molecule that
      inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing
      the glycolytic phenotype in preclinical cancer studies. We designed this open
      label phase II trial to determine the response rate, safety, and tolerability of
      oral DCA in patients with metastatic breast cancer and advanced stage non-small
      cell lung cancer (NSCLC). MATERIALS AND METHODS: This trial was conducted with
      DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV NSCLC or
      stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of
      54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and
      docetaxel) in normoxic and hypoxic conditions. RESULTS AND CONCLUSIONS: Under
      normoxic conditions in vitro, single-agent IC50 was >2 mM for all evaluated cell
      lines. Synergy with cisplatin was seen in some cell lines under hypoxic
      conditions. In the clinical trial, after seven patients were enrolled, the study
      was closed based on safety concerns. The only breast cancer patient had stable
      disease after 8 weeks, quickly followed by progression in the brain. Two patients
      withdrew consent within a week of enrollment. Two patients had disease
      progression prior to the first scheduled scans. Within 1 week of initiating DCA,
      one patient died suddenly of unknown cause and one experienced a fatal pulmonary
      embolism. We conclude that patients with previously treated advanced NSCLC did
      not benefit from oral DCA. In the absence of a larger controlled trial, firm
      conclusions regarding the association between these adverse events and DCA are
      unclear. Further development of DCA should be in patients with longer life
      expectancy, in whom sustained therapeutic levels can be achieved, and potentially
      in combination with cisplatin.

PMID- 24442099
TI  - Clinicopathologic characteristics of ALK rearrangements in primary lung
      adenocarcinoma with identified EGFR and KRAS status.
AB  - PURPOSE: EGFR and KRAS genes and ALK arrangements are three genetic drivers of
      lung adenocarcinoma. The aim of this study was to investigate the
      clinicopathologic characteristics of the ALK rearrangements in patients with
      primary lung adenocarcinoma and with identified EGFR or KRAS status. METHODS:
      Patients with primary lung adenocarcinoma who had enough tissue for study were
      enrolled. EGFR and KRAS status were identified by DNA sequencing. ALK
      rearrangements were detected in a tissue microarray by using fluorescent in situ
      hybridization. RESULTS: Of 332 patients with primary lung adenocarcinoma, the
      frequency of the EGFR or the KRAS mutations, and the ALK rearrangements were
      44.9% (149/332), 7.2% (24/332), and 9.6% (32/332), respectively. Only one (1/332,
      0.3%) patient had the coexistence of the EGFR mutation (L858R at exon 21) and the
      ALK rearrangement. Compared with ALK-negative patients, ALK-positive patients
      were significantly younger (P < 0.001). The incidence of the ALK rearrangements
      was much higher in EGFR wild-type patients than in those with EGFR mutations (P <
      0.001). There was no difference in the gender, smoking, disease stage, or
      histologic subtypes between the ALK-positive patients and the ALK-negative
      patients. CONCLUSIONS: The ALK rearrangements are independently associated with
      younger age and the EGFR wild type. The EGFR mutations and the ALK rearrangements
      are rarely coexistent. The ALK rearrangements and the KRAS mutations are mutually
      exclusive.

PMID- 24442102
TI  - Management of children with diabetes in the school setting.

PMID- 24442103
TI  - Vaccination practices for hepatitis B, influenza, and pneumococcal disease for
      people with diabetes.

PMID- 24442108
TI  - Enhanced visible-light photocatalytic activity of g-C3N4/Zn2GeO4 heterojunctions
      with effective interfaces based on band match.
AB  - Fabricating heterojunction photocatalysts is an important strategy for speeding
      up the separation rate of photogenerated charge carriers, which is attracting
      greater interest. However, the choice of three factors, individual materials,
      band offsets, and effective interfaces, is still important for fabricating
      efficient heterojunction photocatalysts. Herein, efficient g-C3N4/Zn2GeO4
      photocatalysts with effective interfaces were designed by controlling the surface
      charges of the two individual materials inside the same aqueous dispersion
      medium, making use of the electrostatic attraction between oppositely charged
      particles. The g-C3N4/Zn2GeO4 heterojunction with opposite surface charge (OSC)
      showed higher visible-light photocatalytic activity for degradation of methylene
      blue than those of pure g-C3N4, pure Zn2GeO4, and the g-C3N4/Zn2GeO4 with
      identical surface charge (ISC). The investigation of the light absorption
      spectrum, adsorption ability, and photocurrent responses revealed that the
      improved separation of photogenerated carriers was the main reason for the
      enhancement of the OSC g-C3N4/Zn2GeO4 sample's photocatalytic activity. By
      combining with theoretical calculations, we investigated the microscopic
      mechanisms of interface interaction and charge transfer between g-C3N4 and
      Zn2GeO4. The photogenerated electrons in the g-C3N4 N 2p states directly excited
      into the Zn 4s and Ge 4s hybrid states of Zn2GeO4. The strategy of designing and
      preparing a g-C3N4/Zn2GeO4 composite catalyst in this work is very useful for
      fabricating other efficient heterojunction photocatalysts. 

PMID- 24442106
TI  - Smoking, p53 mutation, and lung cancer.
AB  - This issue marks the 50th anniversary of the release of the U.S. Surgeon
      General's Report on Smoking and Health. Perhaps no other singular event has done
      more to highlight the effects of smoking on the development of cancer. Tobacco
      exposure is the leading cause of cancers involving the oral cavity, conductive
      airways, and the lung. Owing to the many carcinogens in tobacco smoke, smoking
      related malignancies have a high genome-wide burden of mutations, including in
      the gene encoding for p53. The p53 protein is the most frequently mutated tumor
      suppressor in cancer, responsible for a range of critical cellular functions that
      are compromised by the presence of a mutation. Herein, we review the
      epidemiologic connection between tobacco exposure and cancer, the molecular basis
      of p53 mutation in lung cancer, and the normal molecular and cellular roles of
      p53 that are abrogated during lung tumor development and progression as defined
      by in vitro and in vivo studies. We also consider the therapeutic potential of
      targeting mutant p53 in a clinical setting based upon the cellular role of mutant
      p53 and data from genetic murine models.

PMID- 24442109
TI  - From the editor.

PMID- 24442110
TI  - Return-to-Work Programs.

PMID- 24442111
TI  - Early Return-to-Work Programs.

PMID- 24442112
TI  - Efficacy of a part-time work hardening program for persons with low-back pain.

PMID- 24442113
TI  - Evaluation of a Model Return-to-Work Program in Texas.

PMID- 24442114
TI  - Effect of music on subjective reports of pain in a work hardening setting.
AB  - Chronic pain can limit a client's ability to participate in the therapeutic
      regime of a work hardening program. Modalities that serve to decrease the pain
      perceived by such clients might increase their ability to benefit from the
      program. The present study was designed to investigate the effects of music on
      clients' pain perception while engaged in a work hardening program. Ten subjects
      from two work hardening programs participated. The data collection period covered
      4 days, during which clients listened to music for 2 days and did not listen to
      music for 2 days while performing their regular work hardening duties. Subjects
      alternated between music and nonmusic days. Data describing clients' perceptions
      of both pain intensity and unpleasantness were gathered every half hour using a
      sliding version of the visual analog scale. Analysis of variance revealed a
      statistically significant lower level of pain perception on days clients listened
      to music versus when they did not listen to music. 

PMID- 24442115
TI  - Returning To Work After Spinal Cord InjuryA Case Study.

PMID- 24442116
TI  - Progressive resistance training program for improving manual materials handling
      performance.

PMID- 24442117
TI  - Refining the practice of ergonomics.

PMID- 24442118
TI  - Role of the Occupational Therapist in an On-Site Occupational Rehabilitation
      ProgramA Case Study.

PMID- 24442119
TI  - The multivocality of health merits a closer look at habilitation of the
      disenfranchised worker.

PMID- 24442120
TI  - The EDI 320.

PMID- 24442121
TI  - Cardiac myosin-binding protein-C is a critical mediator of diastolic function.
AB  - Diastolic dysfunction prominently contributes to heart failure with preserved
      ejection fraction (HFpEF). Owing partly to inadequate understanding, HFpEF does
      not have any effective treatments. Cardiac myosin-binding protein-C (cMyBP-C), a
      component of the thick filament of heart muscle that can modulate cross-bridge
      attachment/detachment cycling process by its phosphorylation status, appears to
      be involved in the diastolic dysfunction associated with HFpEF. In patients,
      cMyBP-C mutations are associated with diastolic dysfunction even in the absence
      of hypertrophy. cMyBP-C deletion mouse models recapitulate diastolic dysfunction
      despite in vitro evidence of uninhibited cross-bridge cycling. Reduced
      phosphorylation of cMyBP-C is also associated with diastolic dysfunction in
      patients. Mouse models of reduced cMyBP-C phosphorylation exhibit diastolic
      dysfunction while cMyBP-C phosphorylation mimetic mouse models show enhanced
      diastolic function. Thus, cMyBP-C phosphorylation mediates diastolic function.
      Experimental results of both cMyBP-C deletion and reduced cMyBP-C phosphorylation
      causing diastolic dysfunction suggest that cMyBP-C phosphorylation level
      modulates cross-bridge detachment rate in relation to ongoing attachment rate to
      mediate relaxation. Consequently, alteration in cMyBP-C regulation of cross
      bridge detachment is a key mechanism that causes diastolic dysfunction.
      Regardless of the exact molecular mechanism, ample clinical and experimental data
      show that cMyBP-C is a critical mediator of diastolic function. Furthermore,
      targeting cMyBP-C phosphorylation holds potential as a future treatment for
      diastolic dysfunction. 

PMID- 24442123
TI  - An archetypal mechanism for branching organogenesis.
AB  - Branched structures are ubiquitous in nature, both in living and non-living
      systems. While the functional benefits of branching organogenesis are
      straightforward, the developmental mechanisms leading to the repeated branching
      of epithelia in surrounding mesoderm remain unclear. Both molecular and physical
      aspects of growth control seem to play a critical role in shape emergence and
      maintenance. On the molecular side, the existence of a gradient of growth
      promoting ligand between epithelial tips and distal mesenchyme seems to be common
      to branched organs. On the physical side, the branching process seems to require
      a mechanism of real-time adaptation to local geometry, as suggested by the self
      avoiding nature of branching events. In this paper, we investigate the outcomes
      of a general three-dimensional growth model, in which epithelial growth is
      implemented as a function of ligand income, while the mesenchyme is considered as
      a proliferating viscous medium. Our results suggest that the existence of a
      gradient of growth-promoting ligand between distal and proximal mesenchyme
      implies a growth instability of the epithelial sheet, resulting in spontaneous
      self-avoiding branching morphogenesis. While the general nature of the model
      prevents one from fitting the development of specific organs, it suggests that
      few ingredients are actually required to achieve branching organogenesis. 

PMID- 24442122
TI  - Function of cGMP-dependent protein kinase II in volume load-induced diuresis.
AB  - Atrial natriuretic peptide (ANP)/cGMPs cause diuresis and natriuresis. Their
      downstream effectors beyond cGMP remain unclear. To elucidate a probable function
      of cGMP-dependent protein kinase II (cGKII), we investigated renal parameters in
      different conditions (basal, salt diets, starving, water load) using a
      genetically modified mouse model (cGKII-KO), but did not detect any striking
      differences between WT and cGKII-KO. Thus, cGKII is proposed to play only a
      marginal role in the adjustment of renal concentration ability to varying salt
      loads without water restriction or starving conditions. When WT mice were
      subjected to a volume load (performed by application of a 10-mM glucose solution
      (3% of BW) via feeding needle), they exhibited a potent diuresis. In contrast,
      urine volume was decreased significantly in cGKII-KO. We showed that AQP2 plasma
      membrane (PM) abundance was reduced for about 50% in WT upon volume load,
      therefore, this might be a main cause for the enhanced diuresis. In contrast,
      cGKII-KO mice almost completely failed to decrease AQP2-PM distribution. This
      significant difference between both genotypes is not induced by an altered p
      Ser256-AQP2 phosphorylation, as phosphorylation at this site decreases similarly
      in WT and KO. Furthermore, sodium excretion was lowered in cGKII-KO mice during
      volume load. In summary, cGKII is only involved to a minor extent in the
      regulation of basal renal concentration ability. By contrast, cGKII-KO mice are
      not able to handle an acute volume load. Our results suggest that membrane
      insertion of AQP2 is inhibited by cGMP/cGKII.

PMID- 24442125
TI  - CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea
      treatment in type 2 diabetes patients.
AB  - PURPOSE: Sulphonylureas (SU) are widely used in the management of type 2
      diabetes. We investigated the influence of CYP2C9, KCNJ11 and ABCC8 polymorphisms
      on the response to SU currently used in everyday clinical practice. METHODS:
      Patients treated for type 2 diabetes with sulphonylurea in monotherapy (n = 21)
      or in combination with metformin (n = 135) were provided with glucose-monitoring
      devices and instructed to measure fasting blood glucose levels once per week and
      additionally at any signs and symptoms suggesting low blood glucose for a period
      of three months. All patients were genotyped for CYP2C9 rs1799853 and rs1057910
      (*2 and *3 allele, respectively), KCNJ11 rs5219 and rs5215, and ABCC8 rs757110.
      RESULTS: The average duration of diabetes in the study group was 10.6 +/- 7.1
      years. Most of the patients achieved relatively good blood glucose control (HbA1c
      7.0 +/- 0.9). In total, 76 hypoglycemia events were observed (mean 0.48 +/- 1.3).
      No severe hypoglycemia was reported; the lowest blood glucose was 2.1 mmol/l.
      Although 124 (79.5 %) patients never experienced hypoglycemia, 32 (20.5 %)
      patients experienced from one to eight events. None of the investigated
      polymorphisms influenced HbA1c levels or risk for hypoglycemia episodes in the
      whole group of patients. CYP2C9 genotype significantly influenced the occurrence
      of hypoglycemia events among the elderly patients (aged 60 years and over; n =
      103). Among them, carriers of two wild-type alleles suffered 0.36 +/- 0.98
      events, while patients with one or two polymorphic alleles had 0.79 +/- 1.7 or
      2.67 +/- 4.6 events, respectively (p = 0.014). CONCLUSIONS: Our results indicate
      that the CYP2C9 genotype may influence the risk for hypoglycemia events in
      elderly patients, but not in the overall population of type 2 diabetes patients.

PMID- 24442127
TI  - Fatal pulmonary embolism following spinal surgery in a patient with permanent
      inferior vena cava filter placement.
AB  - It has been proven that the use of an inferior vena cava filter (IVCF) is
      effective in decreasing the incidence of pulmonary embolism (PE) in high-risk
      spinal surgery patients. A case of fatal PE after spinal surgery in a 78-year-old
      woman who had a history of pulmonary hypertension due to peripheral PE treated
      with a permanent IVCF and anticoagulant therapy for 3 years is reported. The
      patient had experienced an episode of recurrent PE during the withdrawal of
      anticoagulants, but she had uneventfully undergone two orthopedic surgeries with
      a preoperative unfractionated heparin infusion instead of oral warfarin. Three
      months after the second operation, she underwent posterior lumbar spinal fusion.
      The following morning, she suddenly complained of chest discomfort and dyspnea
      with SpO(2) 78 %. An electrocardiogram showed a right bundle branch block. Then,
      30 min later, she suddenly lost consciousness, and her carotid pulse was not
      palpable. The patient died 2 h and 30 min after onset. Acute PE probably occurred
      because of a massive thrombus above the IVCF. This case suggests that the
      efficacy of long- term use of a permanent IVCF is limited in cases when
      anticoagulants must be withdrawn, such as for orthopedic surgery.

PMID- 24442126
TI  - Experimental imaging properties of immersion microscale spherical lenses.
AB  - Using the immersion lensing technique, the resolution of a conventional spherical
      lens can be improved by a factor of 1/n over its value in air (n, the refractive
      index of the immersion medium). Depending on the relative position between an
      object and a lens, either a real or a virtual image is formed. Here we report a
      new physical phenomenon experimentally observed in the microscale lens imaging.
      We find that when a microscale spherical lens is semi-immersed in a medium, the
      resolution of the lens is improved as it can intercept more fine details of the
      object. However, the microscale lens has two image channels for the fine and
      coarse details and two images corresponding to the two components can be formed
      simultaneously. Our findings will advance the understanding of the super
      resolution imaging mechanisms in microscale lenses. 

PMID- 24442128
TI  - Preventive effects of multisensory rehabilitation on development of cognitive
      dysfunction following systemic inflammation in aged rats.
AB  - Systemic inflammation can trigger transient or longer-lasting cognitive
      impairments, particularly in elderly patients. However, its pathogenesis has not
      been sufficiently clarified. In this study, we explored the potential effects of
      multisensory rehabilitation on cognitive dysfunction following systemic
      inflammation using an animal model. Aged male Wister rats were randomly injected
      intraperitoneally with either saline (control) or lipopolysaccharide (LPS; 5
      mg/kg). After injection, both groups of rats were randomly assigned to either of
      two housing conditions (n = 8 in each condition): a standard cage environment (SC
      group) or a multisensory early rehabilitation environment (ER group). Cognitive
      function was examined after 7 days in the assigned environmental condition using
      a novel object recognition test. In the SC group, the LPS-treated rats showed
      impaired cognitive function compared with the control animals. These memory
      deficits were positively correlated with the levels of both tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-1beta in the hippocampus. On the other hand, in
      the LPS-treated ER group, neither cognitive impairment nor an increase in
      hippocampal levels of both TNF-alpha and IL-1beta was found. These results imply
      that early rehabilitation (ER) intervention may be effective in preventing
      cognitive dysfunction following systemic inflammation via its anti
      neuroinflammatory effects. 

PMID- 24442131
TI  - Partial tetra-allel crosses.
AB  - The construction of partical tetra-allel crosses (PTAC) is considered using BIB
      and PBIB designs with blocks of size four. It is shown how this can lead to
      certain types of balanced designs. An explicit procedure is given for
      constructing circulant PTAC's. The analysis of PTAC's - estimation of general
      effects of the lines involved and analysis of variance - is illustrated in terms
      of an example. 

PMID- 24442129
TI  - Effects of a simulation-based sedation training course on non-anesthesiologists'
      attitudes toward sedation and analgesia.
AB  - The purpose of this study was to conduct a survey of emergency or complication
      during sedation and change of attitude toward sedation by simulation-based
      sedation training course (SEDTC) hosted by the Japanese Association of Medical
      Simulation. We used a questionnaire survey to non-anesthesiologists who
      participated in the 1st to 13th SEDTCs from 2011 to 2012. Survey contents
      included emergencies or complications during sedation and impressions of the
      Sedation and Analgesia guidelines for non-anesthesia doctors developed by the
      American Society of Anesthesiologists. Of 84 non-anesthesiologists, 81 have
      encountered patient respiratory suppression. More than 70% non-anesthesiologists
      have encountered patient respiratory arrest. All non-anesthesiologists have
      encountered patient cardiac suppression; 20-30% of non-anesthesiologists have
      encountered patient anaphylaxis, asthma attack, and cardiac arrest; and all non
      anesthesiologists have encountered patient vomiting and about 80% aspiration. Non
      anesthesiologists largely accepted the guidelines. SEDTC attendance improved
      significantly 13 points of 18 important suggestions. As non-anesthesiologists
      experience several complications during sedation, SEDTC may be useful for the
      improvement of their attitude toward the safety management of sedation.

PMID- 24442130
TI  - Patient-derived xenografts reveal limits to PI3K/mTOR- and MEK-mediated
      inhibition of bladder cancer.
AB  - BACKGROUND: Metastatic bladder cancer is a serious condition with a 5-year
      survival rate of approximately 14 %, a rate that has remained unchanged for
      almost three decades. Thus, there is a profound need to identify the driving
      mutations for these aggressive tumors to better determine appropriate treatments.
      Mutational analyses of clinical samples suggest that mutations in either the
      phosphoinositide-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) or
      RAS/MEK/ERK pathways drive bladder cancer progression, although it remains to be
      tested whether the inhibition of either (or both) of these pathways can arrest
      PI3K/mTOR- or Ras-driven proliferation. METHODS: Herein, we used several bladder
      cancer cell lines to determine drug sensitivity according to genetic background
      and also studied mouse models of engrafted UM-UC-3 cells and patient-derived
      xenografts (PDXs) to test PI3K/mTOR and MEK inhibition in vivo. RESULTS:
      Inhibition of these pathways utilizing PF-04691502, a PI3K and mTOR inhibitor,
      and PD-0325901, a MEK inhibitor, slowed the tumor growth of PDX models of bladder
      cancer. The growth inhibitory effect of combination therapy was similar to that
      of the clinical maximum dose of cisplatin; mechanistically, this appeared to
      predominantly occur via drug-induced cytostatic growth inhibition as well as
      diminished vascular endothelial growth factor secretion in the tumor models.
      Kinase arrays of tumors harvested after treatment demonstrated activated p53 and
      Axl as well as STAT1 and STAT3. CONCLUSION: Taken together, these results
      indicate that clinically relevant doses of PF-04691502 and PD-0325901 can
      suppress bladder tumor growth in PDX models, thus offering additional potential
      treatment options by a precision medicine approach.

PMID- 24442132
TI  - [Experiences from laboratory tests with potato breeding material resistant to
      leaf roll virus].
AB  - A description of the laboratory method for testing the resistance of potato
      breeding material to lea roll virus is given. The main steps of this method are
      as follows: Three days after emergence potato plants should be infected with
      potato leaf roll carrying peach aphids.The aphids are separated from feeding
      plants by treating plants and aphids in a refrigerator at -5  degrees C to -7 
      degrees C for two hours. After this, the aphids are distributed into infection
      tubes by a special light box.The results obtained from testing the resistance of
      varieties and breeding material (clonal material and seedling populations) to
      potato leaf roll virus in the laboratory and in the field were compared. Because
      of the positive correlation between the results in the field and laboratory, the
      laboratory method can be recommended for use in practical breeding for leaf roll
      resistance. 

PMID- 24442133
TI  - Breeding of apples for a subtropical climate : II. Analysis of twoF 2 and nine
      backcross populations.
AB  - A report is given on the third phase of a breeding project to produce apples with
      low chilling requirements and high fruit quality. The selection within two F2
      populations and nine BC populations, with Delicious and Jonathan, is described as
      to both methods and results. A description is given of three new subtropical
      apple varieties,MAAYAN, MICHAL andSHLOMIT. 

PMID- 24442134
TI  - [Fertilization and the problem of heterosis in tetraploid red clover].
AB  - Self-fertility in the tetraploid variety Wielkolistna was studied over a period
      of nine years. When the flowers were artificially selfed (heads rolled between
      fingers) seed-setting was on the average 13.61 per head. Weather conditions
      during the flowering period affected very considerably the degree of self
      fertility: favourable conditions promoting better seed-setting. Positive
      correlation coefficients were found (in 1957, 1963, 1964 and 1965) between self
      fertility and seed-setting after free pollination.Inbred lines were established
      and their performance, seed yield and winterhardiness in I1-I4 were analysed. The
      degree of loss in green yield was 20-40%. However, several lines showed a higher
      yield than the controls. Very high uniformity of some features like leaf size and
      color, type of growth and leafiness could be observed already in the F1.To study
      the effect of heterosis the following crosses were performed: inbred lines of red
      clover x inbreds, inbreds x variety Wielkolistna, inbreds x polyploid ecotypes.
      Crosses were made by hand and without emasculation. In all cases no heterosis
      effect was observed and the green yield of the putative hybrids was of the same
      level as that of the inbreds. It could therefore be concluded, that the analysed
      plants were not of hybrid origin but mostly results of self-pollination.In the
      second series of experiments the plants were emasculated before crossing. This
      was done by immersing the flowers in 60% ethyl alcohol for 10 sec., then rinsing
      the heads in water. Seed-setting after use of this method was very poor: 1.08
      seeds per head on the average, due to a damaging effect of the alcohol on female
      gametes. The green yield of the hybrid progeny was in this case much higher than
      that of the plants originating from crosses without emasculation (about 22%
      higher) and from free pollination (13% higher). It could, therefore, be supposed,
      that by artificial crossing without emasculation, and to some extent by free
      pollination, a lot of seeds originate from self-pollination.In using hybrid
      methods it is important to know the degree of self-fertility in a free
      pollinating variety. To study this problem plants without leaf marking, which
      were recessive homozygotes, were choosen and freely pollinated by surrounding
      plants with distinct leaf markings. The number of plant swithout leaf markings in
      the progeny was a direct measure of spontaneous self-fertility. At the same time
      some heads on the mother plants were bagged and rolled between fingrs to get data
      on artificial self-fertility. In 1964 9 progeny and in 1965 25 progeny were
      tested. In the first year spontaneous self-fertility was on the average 28.73%
      and in the second 55.20%. This difference was probably due to different weather
      conditions during the flowering period. They were more suitable in 1963 than in
      1964, when a higher percentage of self-fertilization took place.There was great
      diversity in the degree of self-fertility among the analysed mother plants. Most
      plants were highly self-fertile (their degree of self-fertility being 40-95%).
      There is probably no competition between own and foreign pollen grains when they
      germinate on the stigmas of those plants.The tetraploid variety Wielkolistna can
      therefore be regarded as a partly autogamous population, its degree of self
      fertilization being conditioned by genetical and to some extent external
      factors.The calculated correlation coefficient between spontaneous and artificial
      self-fertility was highly significant:r=+0.714 (P=1%).Plants with leaf markings
      were on the average better in yield than those without them: the green yield of
      the former was 521 g per plant, whereas that of the latter was 454 g (signif.
      withP=1%). The inbreeding depression effect is therefore 12.9 percent.In spite of
      a high degree of self-fertility there exist still some possibilities of applying
      hybrid methods to tetraploid red clover. These are discussed in the paper. 

PMID- 24442135
TI  - Reproduction mode and crop improvement.
AB  - The author has tried to accumulate data on the reproduction modes of crop plants:
      autogamy and allogamy in the case of sexuality, involving self-fertility and self
      sterility, and different means of vegetative propagation and apomixis. In
      combination with the state of ploidy and the basic chromosome number the
      different modes of reproduction exert a considerable influence on population
      structure and the success or failure of different methods applied in plant
      breeding. This relates to the use of selection, hybrid vigour (F1 heterosis),
      gene recombination, as well as polyploidy and induced or spontaneous mutation. It
      is pointed out that extranuclear (cytoplasmic) inheritance should not be
      neglected as a device also in the case of polyploidy and mutation.Transitional
      stages exist between autogamy and allogamy. Autogamy is obligate in no or at
      least very few cases. In allogamous species inbreeding and subsequent outcrossing
      are important features in their improvement by breeding. In dioecious, monoecious
      and hermaphroditic species the modes of reproduction can be switched into one
      another by appropriate methods of gene recombination, mutation and selection.
      Apomictic species, for instance several grasses, display a series of transitions
      between more or less obligatory apomixis (parthenogenesis and vivipary) and
      partial or complete sexuality.At the end of the article data are presented to
      indicate how various modes of reproduction influence the methods applied in the
      exploration and conservation of plant gene pools.Finally, the pioneer work on
      plant exploration carried out byVAVILOV, ZHUKOVSKY and their co-workers is
      emphasized. Favourable genes, chromosomes and cytoplasms present in natural
      populations have to be preserved. New favourable genes etc. should be continually
      produced by mutation. Preservation of old genes and induction of new genes are
      means of augmenting the breeders' resources in their efforts of continuous crop
      plant improvement. 

PMID- 24442136
TI  - [Investigations and proposals for selecting alkaloid-free plants of galega
      varieties by chemical mass selection].
AB  - Different reagents were tested for their usefulness in detecting galegin and
      peganin by chemical mass selection inGalega officinalis. It was shown that
      galegin in lower concentrations, like those obtained by extraction from one leaf
      with 3 ml liquid, could not be precipitated with any amine-and alkaloid-specific
      reagent. Precipitation with a solution of iodine in potassium iodide proved most
      suitable for demonstrating the presence of peganin; the opt mal conditions for
      finding peganin in extracts ofGalega leaves were explored. Ways for selecting
      peganin-poor plants ofGalega orientalis andGalega officinalis by the
      precipitation of peganin with a solution of iodine in potassium iodide are
      discussed. 

PMID- 24442137
TI  - Genetical studies inCajanus cajan (L.) Millsp. : I. Genetics of pod colour.
AB  - From three sets of crosses involving the phenotypes chocolate, red oxide, green
      with chocolate streaks and green with red oxide streaks, the action of the genes
      governing the phenotypes of the pods ofCajanus cajan (L.) Millsp. has been
      proposed. GeneL controls production of chocolate colour,L (r) an allelomorph ofL
      hitherto unreported, controls production of red oxide colour and geneD controls
      distribution of this colour. As regards inheritance of these two genes, the
      relationships betweenL andL (r) isL>L (r) andD is incompletely dominant overd.
      The genotypes of the different phenotypes have been presented. 

PMID- 24442138
TI  - The tragedy of syrinx.
AB  - INTRODUCTION: Today, the term "syrinx" is used by many clinicians. Most users of
      the term, however, are not familiar with the origin of the word. The present
      paper reviews the history of the word syrinx, which is based in Greek mythology.
      CONCLUSIONS: Many modern terms have a derivation that is based on a rich history
      that has often been forgotten. The myth of Syrinx lives on in modern times by the
      continued use of syrinx in various words such as syringomyelia and syringe.

PMID- 24442139
TI  - An unusual location for a choroid plexus papilloma: the pineal region.
AB  - PURPOSE: Choroid plexus papillomas (CPP) are rare benign neoplasms of the central
      nervous system that occur most often in children during the first decade of life.
      They occur most often in the lateral ventricle. It is extremely rare for a CPP to
      occur in the pineal region. We describe the case of a child with a CPP located in
      the pineal region, who was initially diagnosed with obstructive hydrocephalus by
      cranial computed tomography (CT). METHODS: A 9-year-old female patient presented
      with complaints of visual disturbance, nausea, and vomiting. Magnetic resonance
      imaging (MRI) showed a poor contrast-enhanced pineal-localized lesion. Anatomical
      variations within the patient caused her surgery to proceed using a
      supratentorial-occipital interhemispheric approach. RESULTS: The tumor was
      totally removed, and a histological examination revealed the tumor to be a
      typical CPP. The patient received follow-up neurological and ophthalmologic
      examinations at 3, 6, 9, 12, 24, and 36 months postoperatively, which
      demonstrated her progressive improvement. CONCLUSIONS: CPPs may have a wide range
      of locations and resulting symptoms. However, the pineal region is a rarely
      encountered location, particularly for pediatric patients. It is of great value
      to correctly differentiate neoplasms such as germ cell tumors, pineocytomas,
      meningiomas, and astrocytomas, so that patients receive the correct diagnosis and
      treatment approach.

PMID- 24442141
TI  - Is progesterone a neutral or protective factor for breast cancer?

PMID- 24442140
TI  - Beyond E-cadherin: roles of other cadherin superfamily members in cancer.
AB  - Loss of cadherin 1 (CDH1; also known as epithelial cadherin (E-cadherin)) is used
      for the diagnosis and prognosis of epithelial cancers. However, it should not be
      ignored that the superfamily of transmembrane cadherin proteins encompasses more
      than 100 members in humans, including other classical cadherins, numerous
      protocadherins and cadherin-related proteins. Elucidation of their roles in
      suppression versus initiation or progression of various tumour types is a young
      but fascinating field of molecular cancer research. These cadherins are very
      diverse in both structure and function, and their mutual interactions seem to
      influence biological responses in complex and versatile ways. 

PMID- 24442142
TI  - Autophagy: Directed development.

PMID- 24442144
TI  - Reply to Is progesterone a neutral or protective factor for breast cancer?

PMID- 24442143
TI  - The ID proteins: master regulators of cancer stem cells and tumour
      aggressiveness.
AB  - Inhibitor of DNA binding (ID) proteins are transcriptional regulators that
      control the timing of cell fate determination and differentiation in stem and
      progenitor cells during normal development and adult life. ID genes are
      frequently deregulated in many types of human neoplasms, and they endow cancer
      cells with biological features that are hijacked from normal stem cells. The
      ability of ID proteins to function as central 'hubs' for the coordination of
      multiple cancer hallmarks has established these transcriptional regulators as
      therapeutic targets and biomarkers in specific types of human tumours. 

PMID- 24442146
TI  - Combined effects of a high-fat diet and chronic valproic acid treatment on
      hepatic steatosis and hepatotoxicity in rats.
AB  - AIM: To investigate the potential interactive effects of a high-fat diet (HFD)
      and valproic acid (VPA) on hepatic steatosis and hepatotoxicity in rats. METHODS:
      Male SD rats were orally administered VPA (100 or 500 mg.kg-1.d-1) combined with
      HFD or a standard diet for 8 weeks. Blood and liver samples were analyzed to
      determine lipid levels and hepatic function biomarkers using commercial kit
      assays. Low-molecular-weight compounds in serum, urine and bile samples were
      analyzed using a metabonomic approach based on GC/TOF-MS. RESULTS: HFD alone
      induced extensive hepatocyte steatosis and edema in rats, while VPA alone did not
      cause significant liver lesions. VPA significantly aggravated HFD-induced
      accumulation of liver lipids, and caused additional spotty or piecemeal necrosis,
      accompanied by moderate infiltration of inflammatory cells in the liver.
      Metabonomic analysis of serum, urine and bile samples revealed that HFD
      significantly increased the levels of amino acids, free fatty acids (FFAs) and 3
      hydroxy-butanoic acid, whereas VPA markedly decreased the levels of amino acids,
      FFAs and the intermediate products of the tricarboxylic acid cycle (TCA) compared
      with the control group. HFD aggravated VPA-induced inhibition on lipid and amino
      acid metabolism. CONCLUSION: HFD magnifies VPA-induced impairment of
      mitochondrial beta-oxidation of FFAs and TCA, thereby increases hepatic steatosis
      and hepatotoxicity. The results suggest the patients receiving VPA treatment
      should be advised to avoid eating HFD.

PMID- 24442145
TI  - Pheochromocytoma and paraganglioma pathogenesis: learning from genetic
      heterogeneity.
AB  - The neuroendocrine tumours pheochromocytomas and paragangliomas carry the highest
      degree of heritability in human neoplasms, enabling genetic alterations to be
      traced to clinical phenotypes through their transmission in families. Mutations
      in more than a dozen distinct susceptibility genes have implicated multiple
      pathways in these tumours, offering insights into kinase downstream signalling
      interactions and hypoxia regulation, and uncovering links between metabolism,
      epigenetic remodelling and cell growth. These advances extend to co-occurring
      tumours, including renal, thyroid and gastrointestinal malignancies. Hereditary
      pheochromocytomas and paragangliomas are powerful models for recognizing cancer
      driver events, which can be harnessed for diagnostic purposes and for guiding the
      future development of targeted therapies. 

PMID- 24442147
TI  - The effect of inhibition of endoplasmic reticulum stress on lipolysis in white
      adipose tissue in a rat model of chronic kidney disease.
AB  - AIM: Lipolysis in fat tissue plays an important role in the development of
      metabolic disturbances, a characteristic feature of chronic kidney disease (CKD).
      In the present study, we tested the hypothesis that the inhibition of endoplasmic
      reticulum (ER) stress could alleviate lipolysis in white adipose tissue in a rat
      model of CKD. METHODS: A rat model of CKD was established by a method of reduced
      renal mass (RRM). Lipolysis was measured as the release of glycerol in ex vivo
      fat pads and cultured primary adipocytes. The activity of lipases and markers of
      ER stress were measured by Western blotting and immunoprecipitation. RESULTS: Our
      data showed that lipolysis in visceral white adipose tissue was increased in RRM
      rats compared with control rats. In addition, increased phosphorylation of
      hormone-sensitive lipase (HSL) and binding of adipose triglyceride lipase (ATGL)
      to comparative gene identification-58 (CGI-58) protein were observed in the RRM
      rats. The phosphorylation of ER stress markers, including IRE1alpha, PERK, and
      eukaryotic initiation factor (eIF) 2alpha, and the expression of ER stress marker
      78 kDa glucose-regulated protein (GRP78) were significantly increased in RRM
      rats. Treatment with an inhibitor of ER stress partially but significantly
      alleviated lipolysis, and this alleviation was accompanied by reduced binding of
      ATGL to CGI-58. CONCLUSION: Our results showed that enhanced lipolysis and ER
      stress occurred in visceral white adipose tissue in a rat model of CKD. Moreover,
      inhibition of ER stress significantly alleviated lipolysis. These findings
      suggest that ER stress is a potential therapeutic target for the metabolic
      disturbances associated with CKD.

PMID- 24442149
TI  - Earning stripes: myosin binding protein-C interactions with actin.
AB  - Myosin binding protein-C (MyBP-C) was first discovered as an impurity during the
      purification of myosin from skeletal muscle. However, soon after its discovery,
      MyBP-C was also shown to bind actin. While the unique functional implications for
      a protein that could cross-link thick and thin filaments together were
      immediately recognized, most early research nonetheless focused on interactions
      of MyBP-C with the thick filament. This was in part because interactions of MyBP
      C with the thick filament could adequately explain most (but not all) effects of
      MyBP-C on actomyosin interactions and in part because the specificity of actin
      binding was uncertain. However, numerous recent studies have now established that
      MyBP-C can indeed bind to actin through multiple binding sites, some of which are
      highly specific. Many of these interactions involve critical regulatory domains
      of MyBP-C that are also reported to interact with myosin. Here we review current
      evidence supporting MyBP-C interactions with actin and discuss these findings in
      terms of their ability to account for the functional effects of MyBP-C. We
      conclude that the influence of MyBP-C on muscle contraction can be explained
      equally well by interactions with actin as by interactions with myosin. However,
      because data showing that MyBP-C binds to either myosin or actin has come almost
      exclusively from in vitro biochemical studies, the challenge for future studies
      is to define which binding partner(s) MyBP-C interacts with in vivo. 

PMID- 24442150
TI  - Technology.

PMID- 24442148
TI  - Oxymatrine attenuates diabetes-associated cognitive deficits in rats.
AB  - AIM: Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root
      of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse
      pharmacological actions. In this work we investigated the effects of OMT on
      diabetes-associated cognitive decline (DACD) in a rat model of diabetes and
      explored the mechanisms of action. METHODS: Male Wistar rats were injected with
      streptozotocin (65 mg/kg, ip) once to induce diabetes. The rats were then treated
      with vehicle or OMT (60 or 120 mg/kg per day, ip) for 7 weeks. Memory function
      was assessed using Morris water maze test. The levels of malondialdehyde (MDA),
      superoxide dismutase (SOD), glutathione (GSH), NF-kappaB p65 unit, TNF-alpha, IL
      1beta and caspase-3 in the cerebral cortex and hippocampus were quantified.
      RESULTS: The diabetic rats exhibited markedly reduced body weight and increased
      plasma glucose level. The memory function of the rats assessed using Morris water
      maze test showed significant reduction in the percentage of time spent in the
      target quadrant and the number of times crossing the platform, coupled with
      markedly prolongation of escape latency and mean path length. Moreover, the rats
      showed oxidative stress (significantly increased MDA, decreased SOD and reduced
      GSH levels), as well as significant increases of NF-kappaB p65 unit, TNF-alpha,
      IL-1beta and caspase-3 levels in the cerebral cortex and hippocampus. Chronic
      treatment with OMT dose-dependently reversed these behavioral, biochemical and
      molecular changes in the diabetic rats. However, the swimming speed had no
      significant difference among the control, diabetic and OMT-treated diabetic rats.
      CONCLUSION: Chronic treatment with OMT alleviates diabetes-associated cognitive
      decline in rats, which is associated with oxidative stress, inflammation and
      apoptotic cascades.

PMID- 24442151
TI  - Technology transfer: the role of consumer products for individuals with
      disabilities.

PMID- 24442152
TI  - Evaluating reasonable accomodation in the workplace: a team approach.
AB  - Over the course of the past 4 years, a team composed of an occupational therapist
      and a rehabilitation engineer has conducted > 75 evaluations of people with
      disabilities for the California Department of Rehabilitation. These evaluations
      have focused on providing customized solutions to problems of access and
      reasonable accommodation within workplace and classroom settings in accordance
      with the Americans with Disabilities Act regulations and guidelines. This article
      discusses the protocols and evaluation techniques used by the team and the
      underlying philosophy of vocational competence in providing worksite access to
      people with disabilities. 

PMID- 24442153
TI  - A review of ergonomic keyboards.

PMID- 24442155
TI  - Low-Tech Adaptive Design and Fundamentals of TriWall(r) and Plastic Construction.

PMID- 24442154
TI  - Test-retest reliability of the work boxTMa work sample with standard
      instructions.

PMID- 24442156
TI  - Looking at Adaptive Devices through the Eyes of Occupational Therapy.

PMID- 24442157
TI  - Caveat emptor.

PMID- 24442158
TI  - From the editor.

PMID- 24442160
TI  - Computer-aided detection for computed tomographic colonography screening: a
      prospective comparison of a double-reading paradigm with first-reader computer
      aided detection against second-reader computer-aided detection.
AB  - OBJECTIVES: The objective of this study was to prospectively compare diagnostic
      performance and time efficiency of a double-reading paradigm in which a first
      reader computer-aided detection (CAD) is followed by a fast 2-dimensional review
      (DR FR-CAD) with those of a double reading with second-reader CAD (SR CAD).
      MATERIALS AND METHODS: The local ethical committee approved this study.
      Consecutive immunological patients who have positive results for fecal
      immunological test who were scheduled for colonoscopy were enrolled for a 10
      month period. Computed tomographic colonography studies were read with CAD (CAD
      COLON-1.20; im3D, Turin, Italy) by using both SR CAD (applied after unassisted
      interpretation primary 2-dimensional) and DR FR-CAD (CAD-prompts evaluation
      followed by a fast 2-dimensional review) in randomized order with the radiologist
      for each reading paradigm masked to the other reader's results.Per-patient
      sensitivity and specificity of unassisted and CAD-assisted readings for detecting
      6-mm adenomas or larger were calculated by using unblinding colonoscopy as
      reference standard. Reporting times were also calculated. Pairwise comparisons
      were performed. RESULTS: A total of 182 participants (median age, 65 years;
      range, 58-76) were included in the final analysis. Of these, 93 (51%) had at
      least 1 cancer or a 6-mm adenoma or larger. At the 6-mm threshold, sensitivity of
      unassisted reading (79.6%; 95% confidence interval [CI], 69.9-87.2) increased
      significantly with the use of both SR CAD (86.0%; 95% CI, 77.3%-92.3%) and DR FR
      CAD (89.2%; 95% CI, 81.1%-94.7%), without differences between CAD readings (P =
      0.500). No significant differences in specificity among the 3 paradigms were
      observed. Double reading with first-reader CAD required less reading time than
      that for SR CAD (378 vs 496; Delta118 seconds; P < 0.001) and was 59 seconds
      longer than the unassisted reading (P = 0.058). CONCLUSIONS: When compared with
      unassisted reading, a double-reading paradigm in which first-reader CAD is
      followed by a fast 2-dimensional review improves the adenoma detection rate to
      the same level achieved by a second-reader CAD while decreasing reporting times.

PMID- 24442159
TI  - High diversity of human-pathogenic Enterocytozoon bieneusi genotypes in swine in
      northeast China.
AB  - Despite the advances in defining Enterocytozoon bieneusi genotypes worldwide,
      rare genotypic surveys have been documented on this ubiquitous pathogenic
      protozoan in mammals in China, especially the role of pigs in zoonotic
      transmission of microsporidiosis remains unclear. In this study, the distribution
      of E. bieneusi genotypes in 113 duodenal mucosal specimens of pigs with acute
      diarrhea from 15 cities in northeast China was determined by PCR and DNA sequence
      analysis of the ribosomal internal transcribed spacer. The organism was detected
      in 51 (45.1%) pigs from 12 cities, with infection rates of the nursery pigs
      (21/33, 63.6%) significantly higher than the preweaned (25/61, 41.0%; P < 0.05)
      and the growing (5/19, 26.3%; P < 0.01) ones. E. bieneusi belongs to nine known
      human-pathogenic genotypes (D, EbpA, EbpC, EbpD, H, Henan-I, Henan-III, Henan-IV,
      and O) and eight new genotypes (CS-1 to CS-8). Genotypes D, EbpA, EbpC, EbpD,
      Henan-I, Henan-III, and Henan-IV have been found in human infections and D, EbpA,
      EbpC, and EbpD in wastewater in central China. The new genotypes were genetically
      clustered into a group of existing E. bieneusi genotypes with zoonotic potential.
      Considering the discovery of a high prevalence and wide genetic diversity of E.
      bieneusi zoonotic strains in pigs in northeast China and the co-occurrence of
      seven known genotypes in pigs and humans and four in pigs and wastewater, pigs
      probably served as a reservoir for human microsporidiosis and an important source
      of water contamination in China.

PMID- 24442161
TI  - Influence of contrast media viscosity and temperature on injection pressure in
      computed tomographic angiography: a phantom study.
AB  - PURPOSE: Iodinated contrast media (CM) in computed tomographic angiography is
      characterized by its concentration and, consecutively, by its viscosity.
      Viscosity itself is directly influenced by temperature, which will furthermore
      affect injection pressure. Therefore, the purposes of this study were to
      systematically evaluate the viscosity of different CM at different temperatures
      and to assess their impact on injection pressure in a circulation phantom.
      MATERIALS AND METHODS: Initially, viscosity of different contrast media
      concentrations (240, 300, 370, and 400 mgI/mL) was measured at different
      temperatures (20 degrees C-40 degrees C) with a commercially available
      viscosimeter. In the next step, a circulation phantom with physical conditions
      was used. Contrast media were prepared at different temperatures (20 degrees C,
      30 degrees C, 37 degrees C) and injected through a standard 18-gauge needle. All
      other relevant parameters were kept constant (iodine delivery rate, 1.9 g I/s;
      total amount of iodine, 15 g I). Peak flow rate (in milliliter per second) and
      injection pressure (psi) were monitored. Differences in significance were tested
      using the Kruskal-Wallis test (Statistical Package for the Social Sciences).
      RESULTS: Viscosities for iodinated CM of 240, 300, 370, and 400 mg I/mL at 20
      degrees C were 5.1, 9.1, 21.2, and 28.8 mPa.s, respectively, whereas, at 40
      degrees C, these were substantially lower (2.8, 4.4, 8.7, and 11.2 mPa.s). In the
      circulation phantom, mean (SD) peak pressures for CM of 240 mg I/mL at 20 degrees
      C, 30 degrees C, and 37 degrees C were 107 (1.5), 95 (0.6), and 92 (2.1) psi; for
      CM of 300 mg I/mL, 119 (1.5), 104 (0.6), and 100 (3.6) psi; for CM of 370 mg
      I/mL, 150 (0.6), 133 (4.4), and 120 (3.5) psi; and for CM of 400 mg I/mL, 169
      (1.0), 140 (2.1), and 135 (2.9) psi, respectively, with all P values less than
      0.05. CONCLUSIONS: Low concentration, low viscosity, and high temperatures of CM
      are beneficial in terms of injection pressure. This should also be considered for
      individually tailored contrast protocols in daily routine scanning.

PMID- 24442163
TI  - Study on developmental-behavioural pediatrics training experiences of
      pediatricians and pediatric trainees working in Nepal.
AB  - BACKGROUND: There are growing concerns about developmental, behavioural, social
      and emotional wellbeing of children throughout the world. A huge gap exists
      between the instructions provided on medical disciplines and on areas of
      Developmental-Behavioural Pediatrics (DBP) during pediatric training in our
      region. OBJECTIVE: This study aims to evaluate the Developmental-Behavioural
      pediatrics (DBP) training experiences of pediatricians and pediatric trainees
      during their post graduate training in pediatrics. METHODS: Questionnaires were
      sent to the pediatricians / trainees and data was analyzed using SPSS software.
      RESULT: More than 56 % of respondents were satisfied in 10 out of 11 medical
      disciplines whereas more than 56% were unsatisfied in 10 out of 11 developmental
      behavioural pediatrics disciplines. This study has demonstrated that between 50
      60 % of pediatricians did not see the cases of ADHD, learning difficulty and
      family dysfunction for a period of three months prior to the survey which are
      relatively common conditions. Even in post graduate training nearly 66 % of
      pediatricians were unsatisfied with their instructions in DB pediatrics.
      CONCLUSION: Pediatricians working in Nepal have difficulties in addressing the
      issues of developmental pediatrics, raising a question about the need to review
      the curriculum of post graduate training in Pediatrics.

PMID- 24442162
TI  - Ultrasound molecular imaging of transient acute myocardial ischemia with a
      clinically translatable P- and E-selectin targeted contrast agent: correlation
      with the expression of selectins.
AB  - OBJECTIVE: The diagnosis of acute coronary syndrome remains challenging
      especially in patients without clear symptoms or electrocardiographic and/or
      biomarker features. A hallmark of ischemia/reperfusion is activation of
      endothelial cells leading to altered expression of molecular markers, including
      selectins. In this context, we aimed to validate the value of ultrasound
      molecular imaging for detecting transient myocardial ischemia by using a
      clinically translatable dual P- and E-selectin-targeted ultrasound contrast agent
      (UCA) and microbubble (MB(selectin)). MATERIAL AND METHODS: Transient (20
      minutes) myocardial ischemia of rat heart was produced by ligation of the left
      anterior descending coronary artery ligation followed by 2-, 5-, or 24-hour
      reperfusion. Imaging of the transient ischemic event was achieved by the use of
      MB(selectin). Performance of this clinically translatable targeted UCA was
      compared with that of antibody-targeted streptavidin MBs. Finally,
      immunohistochemistry staining of rat myocardial ischemic tissue was performed to
      assess expression of selectins accessible to targeted UCA. RESULTS: In rats
      subjected to myocardial ischemia (20 minutes) followed by reperfusion (2 hours),
      injection of MB(selectin) produced high late phase (ie, 10-minute postinjection)
      ultrasound molecular imaging enhancement in the myocardium, which colocalized
      with the ischemic area. Late phase enhancement persisted 5 and 24 hours after
      reperfusion. Similarly, the use of MBP and MBE, comprising antibodies specific
      for P- and E-selectin, respectively, showed high late-phase enhancement within
      the ischemic area compared with remote myocardial tissue. Two and 5 hours after
      ischemia has resolved, a persistent expression of these 2 selectins was detected.
      After 24 hours of reperfusion, only MBE produced late phase enhancement within
      the ischemic myocardium. Immunohistochemical findings revealed that both P- and E
      selectin were expressed and accessible on the surface of the activated
      endothelium 2 and 5 hours after the acute ischemic event, whereas only E-selectin
      remained accessible after 24 hours. CONCLUSIONS: Ultrasound molecular imaging of
      transient myocardial ischemia using dual selectin-targeted UCA is able to monitor
      the time course of expression of selectins after resolution of the ischemic
      event, paving the way for a large clinical diagnostic window.

PMID- 24442164
TI  - Histomorphological profile of colonoscopic biopsies and pattern of colorectal
      carcinoma in Kavre district.
AB  - BACKGROUND: Colonoscopy is the method to visualize the mucosa of the entire colon
      and terminal ileum to detect the intestinal abnormalities and obtain biopsy for
      definitive diagnosis. For clinical decisions in the diagnosis of various colonic
      lesions unambiguous interpretation of colorectal biopsies is necessary.
      OBJECTIVES: To assess the prevalence pattern of colonic diseases and to correlate
      the incidence of colorectal carcinoma with age, sex, site and symptoms presented
      at Dhulikhel Hospital. METHODS: The materials consisted of 126 biopsies which
      were submitted to the Department of Pathology, Kathmandu University School of
      Medical Sciences, Dhulikhel, during the period of July 2011-July 2012. Data
      collected and entered in MS-Excel and were analyzed using SPSS-16. RESULTS: Out
      of 126 colonoscopic biopsies 34(27%) showed chronic nonspecific inflammation,
      followed by carcinoma 25(19.8%), non-neoplastic polyps 21(16.7%), granulomatous
      inflammation 14(11.1%), neoplastic polyps 8(6.3%), ulcerative colitis 4(3.2%).
      Miscellaneous lesions; acute focal colitis, eosinophilic colitis were also
      observed in 19 (15.1%). A higher frequency of colonic diseases in males with a
      male to female ratio of 1.4:1 and age range of two years to 84 years was
      observed. Out of 25 patients diagnosed with colorectal carcinoma,48% (n=12) were
      males and 52% (n=13) were females with a mean age of 55.17 years in men and 59.46
      years in females. Male and female ratio among cancer groups was 1:1.08. Total 36%
      (n=9) were diagnosed with cancer before the age of 50. Out of these nine cases,
      6( 66.7%) were males and 3(33.3%) were females. The male and female ratio in
      younger and older age groups were 2:1 and 1:1.7 . 17( 68%) of the lesions were
      left sided and 8(32%) were right sided. Below age 50 , left to Right sided
      lesions in males were 2:1 and in females 1:2. However, above 50 years the ratio
      among proximal and distal lesions were 5:1 in males and 2.3:1 in females. A
      statistically significant association was seen between the growth (p=0.000) and
      per rectal bleeding (p= 0.006) with carcinoma. CONCLUSION: The most prevalent
      lesion in colorectal biopsies was non-specific colitis followed by carcinoma
      colon. The incidence of colorectal carcinoma is on rise in Nepalese society.
      Although colorectal carcinoma is more common in older age group the incidence are
      also increasing among young especially among women.

PMID- 24442166
TI  - Correlations between symptoms, nasal endoscopy computed tomography and surgical
      findings in patients with chronic rhinosinusitis.
AB  - BACKGROUND: Although chronic rhinosinusitis (CRS) is increasing in prevalence and
      incidence, its diagnosis and treatment still pose a challenge. The Task Force on
      rhinosinusitis (TFR) advocates the use of symptom based criteria. However, many
      otorhinolaryngologists depend on diagnostic nasal endoscopy and computed
      tomography (CT) of paranasal sinuses for diagnosis of CRS. Computed tomography
      has been extensively relied upon in confirming the presence of CRS, in assessing
      severity of disease, surgical planning and management decisions. Despite its
      widespread use, several studies have failed to correlate findings on CT with
      symptom severity. OBJECTIVE: To determine the correlations between symptoms
      described at presentation, radiological findings, endoscopy and extensiveness of
      surgery. METHODS: Longitudinal, prospective, analytical study conducted from
      August 2011 to August 2012 among 87 patients diagnosed as CRS according to the
      TFR criteria. Symptom, endoscopic, radiological and surgical scoring was done by
      using Lund and Mackay staging system. Pearson correlation coefficients between
      scores for symptoms, endoscopy, sinus CT and surgery was determined. RESULTS:
      When overall symptom score was correlated with radiological score and endoscopy
      score, it was found to be statistically significant (p= <0.01). However, no
      significant relationship was found between Lund and Mackay symptom and surgery
      score. CONCLUSION: The symptom criteria used by TFR for CRS diagnosis are not
      very specific for sinus disease. A detail assessment of the subjective and
      objective criteria (CT and endoscopy) is necessary for tailoring surgical plan
      but should not be relied upon for determining the extensiveness of surgical
      intervention.

PMID- 24442167
TI  - Medical abortion versus manual vacuum aspiration in a hilly district hospital of
      eastern Nepal: a comparative study.
AB  - BACKGROUND: Nepal government has approved medical abortion and manual vacuum
      aspiration for early first trimester pregnancy. Both the procedures have been
      approved by World Health Organization for use in early first trimester.
      OBJECTIVES: The study aims to compare efficacy and safety of medical abortion
      with surgical abortion in a district hospital of rural eastern Nepal. METHOD: An
      observational study conducted in district hospital, Dhankuta from July 2010 to
      January 2011. Clients for abortion services were counseled about methods of
      abortion and were allowed to make decision on their own and classified as medical
      abortion group (N=48) (receiving 200 milligram Mifepristone followed by 800
      microgram misoprostol sublingually or vaginally on day two)and manual vacuum
      aspiration group (N=36). The two groups were compared for rate of complete
      abortion and other complications and contraception use after procedure. RESULTS:
      Rate of complete abortion was similar in both groups, 95.8% among medical
      abortion and 97.2% in manual vacuum aspiration. Moderate to severe expulsion
      bleeding was reported in 91.6% of cases after medical abortion but none required
      medical attention for hemorrhage. Condom was the most preferred contraceptive in
      medical abortion group and depo provera in manual vacuum aspiration group.
      CONCLUSION: Medical method of abortion using mifepristone and misoprostol is
      equally safe and effective as manual vacuum aspiration in rural setting district
      hospitals of Nepal.

PMID- 24442168
TI  - Knowledge and practices on preventive measures of blood borne diseases among non
      medical attendants working in Dhulikhel Hospital, Kathmandu University Hospital.
AB  - BACKGROUND: Blood and certain body fluids pose the greatest threat to health due
      to sharp injuries spreading blood borne pathogens that cause serious illness when
      transmitted. Despite the high sickness rate, sanitation staff lacked awareness
      regarding protections from contacting soiled materials while handling biomedical
      wastes. OBJECTIVE: The study aims to find out the knowledge and practices on
      preventive measures of blood borne diseases among non-medical attendants. Method
      Descriptive cross-sectional study was conducted to find out the knowledge and
      practices on preventive measures on blood borne diseases among all the 53 non
      medical personnel in Dhulikhel Hospital, Kathmandu University Hospital.
      Respondents scoring >=50% on knowledge score were taken as having adequate
      knowledge. A Nepali version of pre-tested structured and semi-structured
      questionnaire was used to conduct interview. Participation in the study was
      voluntary and written consent was taken before inquiry. Outcomes were measured in
      both descriptive and inferential ways. RESULT: The adequate knowledge was found
      among 86.8% of the respondents on the blood borne diseases whereas 50.9% of them
      had proper practice on it. Although, there is poor positive correlation between
      the mean knowledge score and literacy, the correlation was significant (r =
      0.341, p < 0.05). Alike, the mean practice score and work experience demonstrated
      significant correlation (r = 0.319, p <0.05). CONCLUSION: Although knowledge
      score of male was high, female had higher practices score. Both knowledge and
      practice score increased due to the participation in the training programs and
      increment in experience. There was significant positive correlation between the
      mean knowledge score and literacy, and the mean practice score and work
      experience.

PMID- 24442169
TI  - Impact of patch testing on quality of life in patients with hand eczema: a follow
      up study.
AB  - BACKGROUND: Patch testing has previously been shown to influence the quality of
      life, although a very few studies have shown if this is dependent on the result
      of the patch tests. OBJECTIVE: To assess the impact of patch testing on the
      quality of life (QOL) in patients with hand eczema (HE). METHODS: A total of 50
      patients diagnosed of hand eczema at the time of patch testing, aged 16 years and
      above participated in this study. Detailed demographic information and diagnosis
      of hand eczema were collected on the day of the patch test. After six weeks, the
      patients were asked about the hand eczema, knowledge of their allergies and
      change in their life style to avoid the relevant allergens demonstrated on the
      patch test. Dermatology Life Quality Index (DLQI) was used to measure the QOL on
      both occasions. RESULTS: The patch test positivity was found in 68% of patients
      to one or more allergens. The sum score of DLQI at baseline was 12.16 +/- 5.58
      with median 12.0. HE had most impact on symptoms and feelings. Patients with both
      positive patch test (mean baseline= 11.94+/- 5.88; mean at six weeks=2.81+/-
      2.01; P <0.001) and negative patch test (mean baseline=12.63+/- 5.03; mean at 6
      weeks=5.4+/- 3.56; P=0.001) showed significant improvement in DLQI scores,
      however it was more improved in patients with positive patch test than in
      patients with negative patch test. CONCLUSIONS: Hand eczema had an appreciable
      impact on the QOL. Patch testing had been beneficial to most patients in
      improving patient quality of life considerably.

PMID- 24442170
TI  - Ultrastructure of chondrocytes in osteoarthritic femoral articular cartilage.
AB  - BACKGROUND: Osteoarthritis (OA) is a common problem in elderly, but it is not an
      inevitable feature of ageing. About 80-90% of individuals of both sexes have
      radiographic evidence of OA by the time they reach an age of 65. But not all of
      them have the symptoms like pain and decreased joint motion. OBJECTIVE: The
      objective of the present study was conducted to find out whether the
      osteoarthritic changes in human articular cartilage are similar to the ageing
      process or not. METHODS: Femoral articular cartilage specimens obtained from 13
      osteoarthritic patients (52-80 years) undergoing total knee replacement and 9
      cadavers of same age group (50-80 years) (control) were processed and studied
      under electron microscope. The ultrastructure of the cartilage from the two
      groups was compared with each other. RESULTS: Under the electron microscope,
      articular cartilage from control group had chondrocytes having a secretary cell
      characteristic with prominent nucleus and well developed organelles. In
      osteoarthritic cartilage, degenerating or necrotic chondrocytes were found.
      Nuclei of these chondrocytes appeared lobulated or indented. Chondrocytes below
      the fibrillated surface had dilated and irregular endoplasmic reticulum. Electron
      dense lipid deposits in the extracellular matrix as well as intracytoplasmic
      glycogen deposits were much increased in osteoarthritic cartilage as compared to
      the control group. Amount of perinuclear intracytoplasmic fine filaments was also
      increased in the chondrocytes of osteoarthritic cartilage. CONCLUSION:
      Ultrastructural findings of the osteoarthritic articular cartilage were much
      different from the ageing non-osteoarthritic cartilage. Hence, OA should be
      considered a specific process and not simply an inevitable feature of ageing.

PMID- 24442172
TI  - The ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT):
      the correlation of value with underlying severity of alcoholic liver disease.
AB  - BACKGROUND: Alcoholic liver disease is one of the most frequently diagnosed liver
      problems in the hospitalized patients in most tertiary care hospitals all over
      the world .The diagnosis of alcoholic liver disease is most of the time clinical.
      The AST/ALT ratio is a useful and reliable biochemical marker of liver injury due
      to alcohol. Whether the value of AST/ALT ratio correlates with clinical severity
      has not been studied. OBJECTIVES: To study values of AST/ALT ratio in correlation
      with clinical severity of illness due to alcoholic liver disease using Child
      Pugh's grading. METHODS: This is a retrospective study. Inpatient records of all
      the patients admitted with diagnosis of alcoholic liver disease from July 2009 to
      2011 June were analyzed. Data from 174 patients with the diagnosis of alcoholic
      liver disease-alcoholic hepatitis or alcoholic cirrhosis were retrieved; out of
      174 patients, 138 were eligible for the study. The AST/ALT ratio and Child's
      grading of all the patients were calculated from the documented biochemical and
      clinical parameters on admission. Demographic profiles of all the patients were
      also recorded and analyzed. The data was analyzed using software SPPSS 16
      version. RESULTS: A total of 138 patients diagnosed as alcoholic liver disease
      since July 2009 to June 2011 were analyzed. The male-female ratio was found to be
      5.34: 1.The mean age of the patients at diagnosis was found to be 47.58 +/- 12.83
      years. Among 138 patients, Mongolians were found to have the highest prevalence
      of alcoholic liver disease (38.8%), followed by Newars ( 33.6%), Brahmin and
      Chhetri (19.1%) and Dalit (7.2%). With respect to AST/ALT ratio and Child's
      grading of ALD, the mean AST/ALT ratio was found to be 3.03 +/- 2.24 in those
      patients who had Chlild's grade C; likewise the mean AST/ALT ratio was 2.28 +/-
      1.14, and 1.68 +/- 0.83 in patients with Child B and Child A respectively.
      CONCLUSION: The higher value of AST/ALT ratio is indicative of more severe liver
      damage due to alcohol.

PMID- 24442171
TI  - Medication adherence to oral hypoglycemic agents among type II diabetic patients
      and their clinical outcomes with special reference to fasting blood glucose and
      glycosylated hemoglobin levels.
AB  - BACKGROUND: Oral hypoglycemic agents (OHAs) are the major treatment for people
      with type 2 diabetes mellitus (DM2). However, non-adherence to OHAs remains as
      one of the main reasons for poor glycemic control. OBJECTIVES: To assess the
      adherence pattern to OHAs and clinical outcomes with special reference to fasting
      blood glucose (FBG) level and glycosylated hemoglobin (HbA1c) levels. METHODS:
      Informed consent was obtained from patients fulfilling the criteria and from the
      patient party in case of incapacitated patients. Information was obtained by
      interviewing them and filled in the appropriate questionnaire. All the medical
      information of the patients was obtained from the medical case records and
      laboratory reports. RESULTS: OHAs had been discontinued by 25% of patients.
      Overall 38% had ever discontinued and/ or often missed OHAs. Intentional
      discontinuation of OHAs attributed for 72% of the patients, followed by
      forgetfulness (42.9%), carelessness (30.6%), and hypoglycemia, (24%). There were
      50.50% patients who had uncontrolled FBG (>130 mg/dl) level and 39% had
      uncontrolled HbA1c (>= 7%) level. Taking reference age group 51-60 years, control
      of FBG level was found to be statistically associated with the decreasing age
      group (p = 0.006, OR = 4.8) as well as increasing age group (p = 0.008, OR =
      4.034). There was significant association between controlled HbA1c level and
      patients' knowledge about the precautions to be taken while using OHAs (p =
      0.044, OR = 4). However, there was no significant association between glycemic
      control and OHAs adherence. CONCLUSION: Majority of the patients who had missed
      OHAs attributed it to forgetfulness. Hypoglycemia may also be one of the
      contributing factors for poor adherence to OHAs. However no association was found
      between adherence and various other factors like age groups, treatment
      complexity, health literacy and social or family support.

PMID- 24442173
TI  - Role of ultrasound as compared with ERCP in patient with obstructive jaundice.
AB  - BACKGROUND: The diagnosis of obstructive jaundice relies on proper history
      taking, clinical examination, laboratory investigations and different non
      invasive imaging modalities like Ultrasonography (USG), Cholangio Computed
      Tomography (CCT), Magnetic resonance Imaging (MRI) with Magnetic Resonance
      Cholangio Pancreatography (MRCP) and invasive modalities like endoscopic
      retrograde cholangiography (ERCP) and percutaneous trans hepatic cholangiography
      (PTC). OBJECTIVE: To compare the role of ultrasound with endoscopic retrograde
      cholangiography and to determine the major causes of obstructive jaundice in our
      prospect. METHODS: This was a prospective, analytical study conducted on 88
      patients presenting to Department of Radiodiagnosis and Imaging at Dhulikhel
      Hospital-Kathmandu University hospital from March 2011 to August 2012 with
      clinical diagnosis of obstructive jaundice. Sonographic evaluation was performed
      in Siemens acusion x-150 and x-300. The final diagnosis was made by endoscopic
      retrograde cholangiography and /or surgery and confirmed histopathologically.
      RESULTS: The most common benign causes of obstructive jaundice were
      choledocholithiasis (63%), CBD stricture (12.3%), cholangitis (8%) and
      pancreatitis (6.85%) whereas cholangio carcinoma (6.85%) and carcinoma head of
      pancreas (4%) comprised of the malignant causes . Ultrasonography had sensitivity
      of 100% and specificity of 89% in detecting choledocholithiasis. It was found to
      be 98.78% sensitive and 83.33% specific in cholangiocarcinoma. Similarly in
      pancreatitis, the sensitivity of ultrasonography was 97.59% and sensitivity was
      66.67%. CONCLUSION: Ultrasonography acts as a valuable diagnostic imaging
      modality in detecting the causes of obstructive jaundice. Due to its easy
      availability, non invasive nature and cost effectiveness, it can be considered as
      the first line imaging technique/ tool. ERCP is the invasive imaging tool and can
      be used for both diagnostic and therapeutic purpose.

PMID- 24442174
TI  - A comparative study on epidemiology, spectrum and outcome analysis of physical
      trauma cases presenting to emergency department of Dhulikhel Hospital, Kathmandu
      University Hospital and its outreach centers in rural area.
AB  - BACKGROUND: Physical trauma is one of the major cause of mortality and morbidity
      among young and active age group and its increasing trend is of main concern.
      There are only few studies concerning the spectrum of physical trauma in Nepal.
      OBJECTIVE: This study aims to evaluate the epidemiological spectrum, the extent,
      severity of the physical trauma and the outcome evaluation of patients with
      physical trauma over a period of one year in the emergency department of the
      Kathmandu University Hospital and compare the same parameters with those patients
      presenting to the various outreach centers of the hospital in the community.
      METHODS: Patient treatment files from the emergency department and the reports
      from various outreach centers were retrieved for a period of one year (May 2011
      to April 2012). Epidemiological information, mode, type and anatomic location of
      injuries were recorded. Outcome evaluation was assessed by number of patients
      discharged from emergency department of the hospital or the outreach centers
      after the treatment, patients admitted for inpatient management and referred to
      other centers for further specialty management. RESULT: In a period of one year,
      total 2205 (20%) of physical trauma cases presented to the emergency department
      and 1994 (6.12%) in the outreach centres. Most commonly involved age group in
      physical trauma both in Hospital set up and in Community set up were the young
      adults (15 to 49 years). Fall from height was the commonest mode of injury
      followed by road traffic accidents among the patients coming to the hospital
      while significant number of trauma patients coming to outreach centers were due
      to fall from height. In the hospital set up, 1525 (69.2%) of the cases were
      discharged while 537 (24.4%) needed inpatient management and 85 (3.8%) needed
      referral to other centers for the specialty management. In case of outreaches,
      half of the patients were discharged after the primary treatment and almost
      another half were referred to the hospital, mainly for need of further
      investigations. CONCLUSION: Fall related injuries and road traffic accidents are
      the most common mode of trauma in the hospital set up and fall related injuries
      are the single most important mode of trauma seen in the outreaches. Mostly young
      adults in their active period of life are involved in physical trauma so
      appropriate preventive measures through public health approach should be included
      in comprehensive trauma management for reducing mortality and morbidity rates
      related to physical trauma.

PMID- 24442175
TI  - Surgical removal of traumatic herniation of buccal fat pad in young children.
AB  - Intraoral herniation of the buccal fat pad is traumatic lesion of oral cavity
      occurring in young children. It frequently presents as an expanding pedunculated
      mass of soft tissue emanating from the buccal mucosa following a minor trauma to
      the buccal soft tissues. This article aims to report an interesting and rare
      lesion, wherein a tiny traumatic perforation of the buccal mucosa and buccinator
      muscle forced a large portion of the buccal fat pad to extrude into the oral
      cavity in a young boy. Such a situation can alarm any clinician and reinforces
      the importance of careful history taking and thorough examination, before
      treating patients. 

PMID- 24442176
TI  - Fallopian tube papilloma--case report of a rare tumor.
AB  - Fallopian tube neoplasms are rare. We report a rare case of fallopian tube
      papilloma discovered incidentally in a 45 year old female, operated for
      procidentia. Right tube was dilated at the infundibular region, with friable grey
      white tissue in the lumen. Microscopy showed delicate branching papillae lined by
      a single layer of epithelium resembling tubal lining. There were no features to
      suggest a reactive hyperplasia in response to inflammation or of aggressive
      behaviour. 

PMID- 24442177
TI  - Possession syndrome at high altitude ( 4575 m/15000 ft ).
AB  - In a first of its kind, a 20 year old Hindu, highlander, working girl presented
      with abnormal behavior, unrelenting symptoms, had limited benefit by usual
      treatment and was diagnosed as possession syndrome. Exorcism offered symptomatic
      relief. The girl resumed normal activities with no recurrence in a 12 month
      follow up. Possession syndrome is explained in both medical and theological
      perspectives. Modern medicine associates it with a mental illness though True
      Possession syndrome without associated mental illness has been reported.
      Theological perspective can be amalgamated with current scientific theory and
      practice, thereby complimenting existing concepts.

PMID- 24442178
TI  - Non medical interventions for childhood diarrhoea control: way forward in Nepal.
AB  - BACKGROUND: Diarrhoeal diseases remain a major cause of mortality of children
      aged under-five years in the developing countries including Nepal. The
      transmission of diarrhoea mostly caused by biological agents and is facilitated
      by the behavioural, social and environmental factors. More recently, the concept
      of prevention altering these factors is getting momentum. OBJECTIVE: To recommend
      the most effective non medical intervention that can prevent and control
      childhood diarrhoeal disease in Nepal. METHODS: Literature review was conducted
      to analyse the successful interventions in developing countries. Peer review
      articles were accessed from "Science Direct", "Google Scholar", and "PubMed".
      Interventions focussing on social and environmental determinants of diarrhoea
      were included. RESULTS: Four interventions (with primary focus in social and
      environmental determinants of diarrhoeal disease) were purposively selected,
      summarized and discussed. Saniya programme (Burkina Faso 1995 to 1998) is
      considered successful in modifying the risk behaviours. Intensive hand washing
      programme (Pakistan 2002 to 2003), a cluster randomized controlled trail, was not
      sustainable as the results did not last long once the free supply of soap was
      stopped. School Led Total Sanitation (Nepal 2006) is a participatory, community
      centred program whose focus is on local ownership. This program approach is
      effective and feasible for scaling up in Nepal. Global Public Private Partnership
      for Hand washing with Soap (Ghana 2002) was based on the marketing researches and
      hence yielded effective results. CONCLUSION: Combination of School Led Total
      Sanitation and Global Public Private Partnership for hand washing with soap suits
      Nepal. These interventions focus on creating demand, changing behaviour and
      thereby, improving the sanitation status.

PMID- 24442179
TI  - Writing an abstract for a scientific conference.
AB  - For most students and junior researchers, writing an abstract for a poster or
      oral presentation at a conference is the first piece they may write for an
      audience other than their university tutors or examiners. Since some researchers
      struggle with this process we have put together some advice on issues to consider
      when writing a conference abstract. We highlight a number of issues to bear in
      mind when constructing one's abstract. 

PMID- 24442180
TI  - "Sulfolefin": a mixed sulfinamido-olefin ligand in enantioselective rhodium
      catalyzed addition of arylboronic acids to trifluoromethyl ketones.
AB  - Performing catalytic enantioselective carbon-carbon bond forming reactions,
      especially for the synthesis of tertiary carbinols, is one of the most
      challenging goals in modern asymmetric synthesis. Herein, we report an efficient
      enantioselective catalytic approach for the 1,2-addition of arylboronic acids to
      trifluoromethyl ketones affording tertiary trifluoromethyl-substituted alcohols
      with high yields and good enantioselectivities. The reported process uses as a
      catalyst precursor the shelf stable sulfinamido-olefin ligand 1, "sulfolefin",
      obtained on a multigram scale and in one step from a sugar derived sulfinate
      ester.

PMID- 24442181
TI  - Indole-7-carbaldehyde thiosemicarbazone as a flexidentate ligand toward ZnII,
      CdII, PdII and PtII ions: cytotoxic and apoptosis-inducing properties of the PtII
      complex.
AB  - A new thiosemicarbazone (LH2) derived from indole-7-carbaldehyde was synthesized
      and reacted with Zn(II), Cd(II), Pd(II) and Pt(II) salts. The reactions with zinc
      and cadmium salts in 2 : 1 (ligand-metal) molar ratio afforded complexes of the
      type MX2(LH2)2, (X = Cl, Br or OAc), in which the thiosemicarbazone acts as a
      neutral S-monodentate ligand. In the presence of potassium hydroxide, the
      reaction of LH2 with ZnBr2 resulted in deprotonation of the thiosemicarbazone at
      the hydrazine and indole nitrogens to form Zn(L)(CH3OH). The reaction of LH2 with
      K2PdCl4 in the presence of triethylamine, afforded Pd(L)(LH2) which contains two
      thiosemicarbazone ligands: one being dianionic N,N,S-tridentate while the other
      one is neutral S-monodentate. When PdCl2(PPh3)2 was used as the Pd(II) ion
      source, Pd(L)(PPh3) was obtained. In a similar manner, the analogous platinum
      complex, Pt(L)(PPh3), was synthesized. The thiosemicarbazone in the latter two
      complexes behaves in a dianionic N,N,S-tridentate fashion. The platinum complex
      was found to have significant cytotoxicity toward four cancer cells lines, namely
      MDA-MB-231, MCF-7, HT-29, and HCT-116 but not toward the normal liver WRL-68 cell
      line. The apoptosis-inducing properties of the Pt complex was explored through
      fluorescence microscopy visualization, DNA fragmentation analysis and propidium
      iodide flow cytometry. 

PMID- 24442182
TI  - Irreversibility of pressure induced boron speciation change in glass.
AB  - It is known that the coordination number (CN) of atoms or ions in many materials
      increases through application of sufficiently high pressure. This also applies to
      glassy materials. In boron-containing glasses, trigonal BO3 units can be
      transformed into tetrahedral BO4 under pressure. However, one of the key
      questions is whether the pressure-quenched CN change in glass is reversible upon
      annealing below the ambient glass transition temperature (Tg). Here we address
      this issue by performing (11)B NMR measurements on a soda lime borate glass that
      has been pressure-quenched at ~0.6 GPa near Tg. The results show a remarkable
      phenomenon, i.e., upon annealing at 0.9Tg the pressure-induced change in CN
      remains unchanged, while the pressurised values of macroscopic properties such as
      density, refractive index, and hardness are relaxing. This suggests that the
      pressure-induced changes in macroscopic properties of soda lime borate glasses
      compressed up to ~0.6 GPa are not attributed to changes in the short-range order
      in the glass, but rather to changes in overall atomic packing density and medium
      range structures. 

PMID- 24442183
TI  - Minimally invasive surgery for lumbar disc herniation: a systematic review and
      meta-analysis.
AB  - PURPOSE: Assessing the benefits of surgical treatments for sciatica is critical
      for clinical and policy decision-making. To compare minimally invasive (MI) and
      conventional microdiscectomy (MD) for patients with sciatica due to lumbar disc
      herniation. METHODS: A systematic review and meta-analysis of controlled clinical
      trials including patients with sciatica due to lumbar disc herniation.
      Conventional microdiscectomy was compared separately with: (1) Interlaminar MI
      discectomy (ILMI vs. MD); (2) Transforaminal MI discectomy (TFMI vs. MD).
      OUTCOMES: Back pain, leg pain, function, improvement, work status, operative
      time, blood loss, length of hospital stay, complications, reoperations,
      analgesics and cost outcomes were extracted and risk of bias assessed. Pooled
      effect estimates were calculated using random effect meta-analysis. RESULTS:
      Twenty-nine studies, 16 RCTs and 13 non-randomised studies (n = 4,472), were
      included. Clinical outcomes were not different between the surgery types. There
      is low quality evidence that ILMI takes 11 min longer, results in 52 ml less
      blood loss and reduces mean length of hospital stay by 1.5 days. There were no
      differences in complications or reoperations. The main limitations were high risk
      of bias, low number of studies and small sample sizes comparing TF with MD.
      CONCLUSIONS: There is moderate to low quality evidence of no differences in
      clinical outcomes between MI surgery and conventional microdiscectomy for
      patients with sciatica due to lumbar disc herniation. Studies comparing
      transforaminal MI with conventional surgery with sufficient sample size and
      methodological robustness are lacking.

PMID- 24442184
TI  - Answer to the second letter to the Editor of J. Padulo et al. concerning:
      "vertebral rotation in adolescent idiopathic scoliosis calculated by radiograph
      and back surface analysis-based methods: correlation between the Raimondi method
      and rasterstereography" by Mangone M, Raimondi P, Paoloni M, Pellanera S, Di MA,
      Di RS, Vanadia M, Dimaggio M, Murgia M, Santilli V (2013) Eur Spine J 22:367-371.

PMID- 24442185
TI  - Answer to the Letter to the Editor of Feng Li et al. entitled "Minimally invasive
      versus open transforaminal lumbar interbody fusion: a meta-analysis based on the
      current evidence" by Nai-Feng Tian, Yao-Sen Wu, Xiao-Lei Zhang, Hua-Zi Xu, Yong
      Long Chi, Fang-Min Mao (2013). Eur Spine J, doi:10.1007/s00586-013-2747-z.

PMID- 24442186
TI  - Treatment with coated layer double hydroxide clays decreases the toxicity of
      copper-contaminated water.
AB  - Copper is a common pollutant found in watersheds that exerts toxic effects on
      both invertebrates and vertebrates. Layer double hydroxide (LDH) clays are able
      to adsorb a wide range of contaminants through ion-exchange mechanisms. Coating
      LDH clays with various materials alters the aggregation of clay particles into
      the nano-size range, thus increasing relative surface area and offering great
      potential for contaminant remediation. The goal of this study was to determine if
      treatment with coated LDH clays decreases the toxicity of copper-containing
      solutions to Daphnia magna. Four LDH clays with different coatings used to alter
      hydrophobicity were as follows: used: Na(+) montmorillonite, Zn-Al LDH-nitrate,
      Zn-Al LDH-stearate, and Zn-Al LDH-carbonate. It was determined that coated LDH
      clays decreased copper toxicity by decreasing bioavailability and that smaller
      aggregate sizes decreased bioavailability the most. 96 h LC50 values increased by
      as much as 4.2 times with the treatment of the solutions with 100 mg/L LDH clay.
      Copper analysis of the clay and solutions indicated that the clays work by
      decreasing copper bioavailability by way of a binding mechanism. Coated LDH clays
      hold promise as a small-scale remediation tool or as an innovative tool for
      toxicity identification and evaluation characterization of metals.

PMID- 24442187
TI  - Unravelling the proteome of adult rhesus monkey ovaries.
AB  - Ovarian physiology and pathology are important areas of scientific research.
      Efforts have been made to identify the ovary-related transcriptomes in different
      species. However, the proteomic studies are limited. The rhesus monkey is very
      similar to humans, and it is widely used in the study of reproductive biology and
      medicine. In this study, using an optimized proteomics platform, we successfully
      identified 5723 rhesus ovarian proteins, of which 4325 proteins were consistently
      identified in all three replicates and with at least 2 unique peptides. The 4325
      proteins were chosen for further analysis. Through gene ontology and pathway
      analyses, we obtained a preliminary understanding of the function of these
      proteins. A random immunohistochemistry analysis was used to determine the
      expression of proteins in various cell types. By comparing the genes identified
      in this study with genes that were reported to have relatively high levels of
      expression in human oocytes, we obtained genes that were predicted to play roles
      in maintenance of normal ovarian physiology. Searching the identified genes from
      this study against the MGI database gave us a list of proteins those exist in the
      rhesus monkey ovary and are important for female mouse reproduction as well. The
      overlap of genes in this study and the genes whose abnormal expression or
      dysfunction were reported to be associated with human polycystic ovary syndrome
      (PCOS) and premature ovarian failure (POF) prompted us to use the rhesus monkey
      to study these two common causes of female infertility. This study may provide a
      basis for future studies of human reproductive disorders using the rhesus monkey
      as a model. 

PMID- 24442188
TI  - Hepatocellular carcinoma with colonic metastasis.
AB  - Hepatocellular carcinoma with colonic metastasis is rare. It mainly occurs by
      direct invasion and presents with bloody stools. We describe a patient with
      haematogenous metastasis to the rectum who presented with tenesmus. To our
      knowledge, such an association has not been reported previously. Colonic
      metastasis should be considered when patients with hepatocellular carcinoma
      present with bloody stools or tenesmus.

PMID- 24442189
TI  - Diagnosing features of Jacobson's nerve schwannoma.
AB  - Jacobson's nerve schwannoma is a rare middle ear tumour presenting as a mass
      along the cochlear promontory. It can be differentiated from other masses along
      the promontory based on clinical findings, and computed tomography and magnetic
      resonance imaging features. For small-sized masses, it is possible to
      differentiate the various middle ear schwannomas from one another. We present the
      case of a 40-year-old woman with a ten-year history of left hearing loss who was
      diagnosed with Jacobson's nerve schwannoma.

PMID- 24442190
TI  - Primary soft tissue Ewing's sarcoma of the maxillary sinus in elderly patients:
      presentation, management and prognosis.
AB  - Nonosseous or soft tissue Ewing's sarcoma is a rare form of Ewing's
      sarcoma/primitive neuroectodermal tumour that seldom affects the head and neck
      region. Involvement of the nose and paranasal sinuses is extremely uncommon, with
      only eight of such patients being reported to date, mostly affecting adolescents
      and young adults. To our knowledge, this study is the first comprehensive report
      of primary soft tissue Ewing's sarcoma involving the paranasal sinuses in an
      elderly patient who successfully completed treatment. We herein discuss the
      pathogenesis, management and factors affecting the prognosis of this rare group
      of tumours involving the nose and paranasal sinuses, in relation to the available
      literature.

PMID- 24442191
TI  - Characterization of bacterial diversity associated with microbial mats, gypsum
      evaporites and carbonate microbialites in thalassic wetlands: Tebenquiche and La
      Brava, Salar de Atacama, Chile.
AB  - In this paper, we report the presence of sedimentary microbial ecosystems in
      wetlands of the Salar de Atacama. These laminated systems, which bind, trap and
      precipitate mineral include: microbial mats at Laguna Tebenquiche and Laguna La
      Brava, gypsum domes at Tebenquiche and carbonate microbialites at La Brava.
      Microbial diversity and key biogeochemical characteristics of both lakes (La
      Brava and Tebenquiche) and their various microbial ecosystems (non-lithifying
      mats, flat and domal microbialites) were determined. The composition and
      abundance of minerals ranged from trapped and bound halite in organic-rich non
      lithifying mats to aragonite-dominated lithified flat microbialites and gypsum in
      lithified domal structures. Pyrosequencing of the V4 region of the 16s rDNA gene
      showed that Proteobacteria comprised a major phylum in all of the microbial
      ecosystems studied, with a marked lower abundance in the non-lithifying mats. A
      higher proportion of Bacteroidetes was present in Tebenquiche sediments compared
      to La Brava samples. The concentration of pigments, particularly that of
      Chlorophyll a, was higher in the Tebenquiche than in La Brava. Pigments typically
      associated with anoxygenic phototrophic bacteria were present in lower amounts.
      Organic-rich, non-lithifying microbial mats frequently formed snake-like, bulbous
      structures due to gas accumulation underneath the mat. We hypothesize that the
      lithified microbialites might have developed from these snake-like microbial mats
      following mineral precipitation in the surface layer, producing domes with
      endoevaporitic communities in Tebenquiche and carbonate platforms in La Brava.
      Whereas the potential role of microbes in carbonate platforms is well
      established, the contribution of endoevaporitic microbes to formation of gypsum
      domes needs further investigation. 

PMID- 24442192
TI  - Halorubrum halophilum sp. nov., an extremely halophilic archaeon isolated from a
      salt-fermented seafood.
AB  - A novel, red-pigmented, pleomorphic and short rod-shaped haloarchaeon, designated
      B8(T), was isolated from a salt-fermented seafood. Strain B8(T) was found to be
      able to grow at 20-45  degrees C, in the presence of 15-30 % (w/v) NaCl and at pH
      7.0-9.0. The optimum requirements were found to be a temperature range of 35-40 
      degrees C, pH 8.0 and the presence of 25 % NaCl. The cells of strain B8(T) were
      observed to be Gram-staining negative and lysed in distilled water. Anaerobic
      growth did not occur in the presence of nitrate, L-arginine, dimethyl sulfoxide
      or trimethylamine N-oxide. The catalase and oxidase activities were found to be
      positive and nitrate was reduced in aerobic conditions. Tween 20, 40 and 80 were
      found to be hydrolyzed, whereas casein, gelatin and starch were not hydrolyzed.
      Indole or H2S was not formed and urease activity was not detected. A phylogenetic
      analysis based on the 16S rRNA gene sequences indicated that strain B8(T) is most
      closely related to members of the genus Halorubrum in the family
      Halobacteriaceae. Strain B8(T) was found to have three 16S rRNA genes, rrnA, rrnB
      and rrnC; similarities between the 16S rRNA gene sequences are 99.0-99.8 %.
      Strain B8(T) shared 99.0 % 16S rRNA gene sequence similarity with Halorubrum
      (Hrr.) lipolyticum JCM 13559(T) and Hrr. saccharovorum DSM 1137(T), 98.8 % with
      Hrr. kocurii JCM 14978(T), 98.3 % with Hrr. lacusprofundi DSM 5036(T), 98.0 %
      with Hrr. arcis JCM 13916(T), 97.7 % with Hrr. aidingense JCM 13560(T) and 97.0 %
      with Hrr. aquaticum JCM 14031(T), as well as 93.7-96.5 % with other type strains
      in the genus Halorubrum. The RNA polymerase subunit B' gene sequence similarity
      of strain B8(T) with Hrr. kocurii JCM 14978(T) is 97.2 % and lower with other
      members of the genus Halorubrum. DNA-DNA hybridization experiments showed that
      strain B8(T) shared equal or lower than 50 % relatedness with reference species
      in the genus Halorubrum. The genomic DNA G+C content of strain B8(T) was
      determined to be 64.6 mol%. The major isoprenoid quinone of strain B8(T) was
      identified as menaquinone-8 and the major polar lipids as phosphatidylglycerol,
      phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate,
      sulfated mannosyl glucosyl diether and an unidentified phospholipid. Based on
      this polyphasic taxonomic study, strain B8(T) is considered to represent a new
      species in the genus Halorubrum, for which the name Hrr. halophilum sp. nov. is
      proposed. The type strain is B8(T) (=JCM 18963(T) = CECT 8278(T)).

PMID- 24442193
TI  - Synergistic effect of calcium and kinetin on ethylene production by the mungbean
      hypocotyl.
AB  - A slight increase in ethylene production resulted from the application of either
      kinetin or Ca(2+) to mungbean (Phaseolus mungo L.) hypocotyl segments, but a
      remarkable synergistic increase in C2H4 production was observed when they were
      applied together. The induction time was about 6 h as compared to 1 h for auxin
      induced C2H4 production. A slight stimulation of C2H4 production was also
      observed when Ca(2+) was applied with abscisic acid, but no synergistic effect of
      Ca(2+) was observed with indole-3-acetic acid or GA3. 

PMID- 24442194
TI  - [The effect of auxin and cytokinin on RNA-synthesis in sterile tobacco tissue].
AB  - The influence of auxin and cytokinin on RNA synthesis was investigated by
      measuring (32)PO4 (3-)-incorporation into polysomes and polysomal RNAs of tissue
      grown from pith of Nicotiana tabacum L. The test tissue grown on a medium
      containing a minimum of auxin and cytokinin was further starved for a period of
      12 h prior to the experiments. The tests were carried out under the following
      different conditions: 1. without any growth substances, 2. with auxin only, 3.
      with kinetin only, and 4. with auxin and kinetin. The tissues were incubated in
      small volumes of the test medium for 1-8 h on a shaker. The last hour of
      incubation was carried out in the presence of (32)PO4 (3-).Differences in (32)PO4
      (3-) uptake into the polysomes were observed as early as after 3 h of incubation.
      Kinetin alone shows no effect at all, auxin causes increased synthesis of
      polysomal RNAs, and kinetin administered together with auxin augments the
      increase of (32)PO4 (3-) uptake into polysomes and polysomal RNAs observed with
      auxin alone. These results and those of Seth and Wareing [J. exp. Bot. 18, 65-77
      (1967)], Bhattacharyya and Roy [Biochem. biophys. Res. Commun. 35, 606-610
      (1969)], and Venis [Proc. nat. Acad. Sci. (Wash.) 68, 1824-1827 (1971)] lead to
      the following working hypothesis: while auxins exert their influence on the RNA
      transcription, cytokinins may possibly influence the translation process. 

PMID- 24442195
TI  - Metabolically labile DNA in aseptically grown seedlings of Pisum sativum L.
AB  - Pea seedlings (Pisum sativum L.) were grown aseptically in a sterile flexible
      film animal isolator. Radioactivity from [Me-(3)H]thymidine, supplied to the
      roots of the seedlings, was specifically incorporated into pea DNA. There was no
      incorporation into RNA or into bacterial DNA; neither was there any non-specific
      binding of label to carbohydrate. Much of the radioactivity incorporated into the
      DNA was lost during a cold chase. The loss could not be accounted for by net DNA
      synthesis and cell division, and is therefore taken as strong evidence for DNA
      turnover. The significance of these results is discussed. 

PMID- 24442196
TI  - [Localisation of tryptophan synthetase in etioplasts of Pisum sativum L].
AB  - Tryptophan synthetase from buds of pea seedlings is associated with a particulate
      fraction. By centrifugation on a continuous sucrose gradient and electron
      microscopy it is shown that the enzyme is localized in etioplasts. 

PMID- 24442197
TI  - [Distribution of microbody enzymes from Chlamydomonas on sucrose gradients].
AB  - The crude homogenate of cells from Chlamydomonas reinhardii was placed on a
      linear gradient from 30% to 60% sucrose and centrifuged for 4 hours at 60 000 g.
      After fractionation of the gradient the distribution of enzymes was determined.
      Hydroxypyruvate reductase and glycolate dehydrogenase, two markers for
      peroxisomes, appeared with one sharp peak at density 1.185 g/cm(3) within the
      gradient. Twenty-five percent of the hydroxypyruvate reductase was particulate
      and 75% was found as solubles in the top fractions. The peaks of both enzymes
      matched exactly the peak of the cytochrome oxidase which is a marker for
      mitochondria. The profile for malate dehydrogenase was the same as that for
      hydroxypyruvate reductase. Catalase, however, showed two peaks. One coincided
      with the peak of cytochrome oxidase and the other appeared at density 1.22
      g/cm(3). More than 50% of the catalase moved into the gradient during
      centrifugation. 

PMID- 24442198
TI  - Development of tuberous roots and sugar accumulation as related to invertase
      activity and mineral nutrition.
AB  - Sucrose storage in tuberous roots was not observed when the tissues had very high
      activities of acid invertase. High activities of the enzyme were always present
      in the roots at early stages of their development. In species where the activity
      of the enzyme decreased during root development, sucrose was stored. Thus, acid
      invertase was undetectable in mature roots of carrots (Daucus carota L.) where
      sucrose formed almost 80% of the dry matter. Conversely, radish (Raphanus sativus
      L.) and turnip (Brassica rapa L.) roots, in which the activity of the enzyme
      remained high until maturity, did not store appreciable amounts of sucrose (2%
      and 9%, respectively, of the dry matter in the mature roots), reducing sugars
      being the main reserve (more than 80% of the dry matter in mature turnips). The
      correlation between sucrose content and acid invertase activity was furthermore
      evident in both sucrose- and hexose-storing roots when the activity of this
      enzyme was affected by changes in the mineral nutrition. Deficiencies of nitrogen
      and sulphur reduced the activity of acid and alkaline invertases and led to
      increase in sucrose content and decrease in reducing sugars. However, the decline
      of alkaline invertase activity in tissues low in acid invertase had no clear
      effect on sugar content. Sodium chloride (10(-1)M) affected acid invertase and
      sugars in a manner similar to that of the two deficiencies, but had practically
      no effect on alkaline invertase. The changes in sugar content produced by the
      variations in mineral nutrition were small in hexose-storing roots in relation to
      those of sucrose-storing roots. It is possible that this result is related to the
      different levels of acid invertase in the two types of roots. 

PMID- 24442199
TI  - Selective inhibition of mesophyll chloroplast development in some C4-pathway
      species by low night temperature.
AB  - Exposure of plants of Sorghum bicolor L. line E 1287 and hybrid NK 145, of
      Digitaria smutsii Stapf, and of Paspalum dilatatum L.-grasses having the C4
      pathway of photosynthesis-to temperatures of 4 degrees , 2.5 degrees , 2.5
      degrees  and-3 degrees , respectively, for a single night caused the formation
      within 36 h of transverse, irreversibly chlorotic bands on emerging leaves.
      Chlorosis was associated with the presence of chlorophyll-deficient, structurally
      abnormal plastids in most mesophyll cells, whereas chloroplasts in adjacent
      bundle-sheath cells were green and possessed a normal lamellar structure. The
      ultrastructure of other organelles in the chlorotic mesophyll cells appeared
      normal and the levels of cytoplasmic rRNA, non-plastid lipids and isocitrate
      dehydrogenase were similar or slightly higher in chlorotic compared with green
      lamina. The content of chloroplast rRNA and plastid lipids in the chlorotic
      tissue was low. Activities of all C4-pathway enzymes examined were lower in the
      chlorotic tissue but phosphopyruvate carboxylase, NADP-malate dehydrogenase and
      adenylate kinase were reduced to a greater extent than ribulose diphosphate
      carboxylase, fructose diphosphate aldolase and malic enzyme. The region of
      emerging leaves that contained mesophyll plastids susceptible to low temperature
      was identified and the stages of plastid ontogeny below, within and above this
      region examined. During normal differentiation rapid increases in plastid size
      and in the content of chloroplast rRNA, chlorophyll, plastid lipids and in the
      activities of C4-pathway enzymes occur at a developmental stage subsequent to
      that at which plastids are susceptible to low temperature. 

PMID- 24442200
TI  - Determination of specific growth stages of plant cell suspension cultures by
      monitoring conductivity changes in the medium.
AB  - Conductivity changes in the medium of cultured soybean (Glycine max L.) cells
      were shown to be strictly correlated with nitrate uptake and growth of the
      cultures. A continuous record of the conductivity was used as a simple and
      reliable method of determining specific growth stages and concomitant peaks in
      the activities of nitrate reductase and phenylalanine ammonia-lyase. 

PMID- 24442201
TI  - No polysaccharide demonstrated in filamentous structures in sieve elements by
      theiry's periodic acid-thiocarbohydrazide-silver proteinate method for electron
      microscopy.
AB  - By means of Thiery's Periodic acid-thiocarbohydrazide-silver proteinate method,
      for electron microscopy, it has been demonstrated that the filamentous structures
      of sieve elements contain no polysaccharide component. 

PMID- 24442202
TI  - Crassulacean acid metabolism in Lithops insularis; a non-halophytic member of the
      Mesembryanthemaceae.
AB  - Lithops insularis, a non-halophytic member of the Mesembryanthemaceae, is shown
      to exhibit major features if crassulacean acid metabolism. Data are presented
      which demonstrate the accumulation, by this plant, of malic acid synthesised in
      darkness from carbon dioxide. 

PMID- 24442203
TI  - Halogen effects on photoluminescence and catalytic properties: a series of
      spatially arranged trimetallic zinc(II) complexes.
AB  - Self-assembly of ZnX2 (X = Cl, Br, and I) with N,N',N''-tris(2-pyridinylethyl)
      1,3,5-benzenetricarboxamide (L) as a tridentate N-donor ligand yields discrete C3
      symmetric trimetallic zinc(II) complexes, [Zn3X6L(MeOH)3]. These form, via
      pi???pi interactions and NH????O=C hydrogen-bonds, an ensemble constituting a
      unique columnar stacking structure in an abab staggered fashion. For this series
      of complexes, the halogen effects on the photoluminescence, catalysis, and
      thermal properties were investigated. For [Zn3Cl6L(MeOH)3], a blue luminescence
      was observed at 462 nm (lambdaex = 369 nm). The transesterification catalysis
      showed significant halogen effects in the order [Zn3I6L(MeOH)3] >
      [Zn3Cl6L(MeOH)3] > [Zn3Br6L(MeOH)3] in methanol, whereas in a mixture of methanol
      and acetonitrile, the order was [Zn3I6L(MeOH)3] > [Zn3Br6L(MeOH)3] >
      [Zn3Cl6L(MeOH)3]. Such notable different effects among the three complexes might
      be explained by the halogens' electronic effects and dissociation properties.

PMID- 24442205
TI  - Highly aggressive T-cell acute lymphoblastic leukemia with t(8;14)(q24;q11):
      extensive genetic characterization and achievement of early molecular remission
      and long-term survival in an adult patient.

PMID- 24442204
TI  - GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic
      target.
AB  - Multiple myeloma (MM) is an incurable haematological malignancy characterised by
      the proliferation of mature antibody-secreting plasma B cells in the bone marrow.
      MM can arise from initiating translocations, of which the musculoaponeurotic
      fibrosarcoma (MAF) family is implicated in ~5%. MMs bearing Maf translocations
      are of poor prognosis. These translocations are associated with elevated Maf
      expression, including c-MAF, MAFB and MAFA, and with t(14;16) and t(14;20)
      translocations, involving c-MAF and MAFB, respectively. c-MAF is also
      overexpressed in MM through MEK/ERK activation, bringing the number of MMs driven
      by the deregulation of a Maf gene close to 50%. Here we demonstrate that MAFB and
      c-MAF are phosphorylated by the Ser/Thr kinase GSK3 in human MM cell lines. We
      show that LiCl-induced GSK3 inhibition targets these phosphorylations and
      specifically decreases proliferation and colony formation of Maf-expressing MM
      cell lines. Interestingly, bortezomib induced stabilisation of Maf
      phosphorylation, an observation that could explain, at least partially, the low
      efficacy of bortezomib for patients carrying Maf translocations. Thus, GSK3
      inhibition could represent a new therapeutic approach for these patients. 

PMID- 24442206
TI  - Dynamics of ASXL1 mutation and other associated genetic alterations during
      disease progression in patients with primary myelodysplastic syndrome.
AB  - Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were
      identified in patients with myelodysplastic syndrome (MDS), but the interaction
      of this mutation with other genetic alterations and its dynamic changes during
      disease progression remain to be determined. In this study, ASXL1 mutations were
      identified in 106 (22.7%) of the 466 patients with primary MDS based on the
      French-American-British (FAB) classification and 62 (17.1%) of the 362 patients
      based on the World Health Organization (WHO) classification. ASXL1 mutation was
      closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2,
      SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1
      mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1
      mutation was an independent poor prognostic factor for survival. Sequential
      studies showed that the original ASXL1 mutation remained unchanged at disease
      progression in all 32 ASXL1-mutated patients but were frequently accompanied with
      acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1,
      SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild
      patients, only one acquired ASXL1 mutation at leukemia transformation. In
      conclusion, ASXL1 mutations in association with other genetic alterations may
      have a role in the development of MDS but contribute little to disease
      progression. 

PMID- 24442208
TI  - Water/alcohol soluble electron injection material containing azacrown ether
      groups: synthesis, characterization and application to enhancement of
      electroluminescence.
AB  - Using an environmentally stable metal as the cathode in a polymer light-emitting
      diode (PLED) is an essential requirement for its practical application. We
      present the preparation of a water/alcohol soluble copoly(p-phenylene) (P1)
      containing pendant azacrown ether and ethylene glycol ether groups as a highly
      efficient electron injection layer (EIL) for PLEDs, allowing the use of
      environmentally stable aluminum as the cathode. Multilayer PLEDs
      [ITO/PEDOT:PSS/PF-Green-B/EIL/Al] using P1 as EIL exhibit significantly enhanced
      device performance, particularly in the presence of K2CO3 or Cs2CO3. The maximum
      luminous power efficiency and maximum luminance of the device with Cs2CO3-doped
      P1 as EIL were enhanced to 9.16 lm W(-1) and 17,050 cd m(-2), respectively,
      compared with those without EIL (0.16 lm W(-1), 890 cd m(-2)). The turn-on
      voltage was also significantly reduced from 5.7 V to 3.7 V simultaneously. The
      performance enhancement has been attributed to improved electron injection which
      has been confirmed by the rise in open-circuit voltage (Voc) obtained from
      photovoltaic measurements. The incorporation of such an electron injection layer
      significantly enhances device performance for PLEDs with an environmentally
      stable metal as the cathode.

PMID- 24442207
TI  - Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/beta-catenin
      pathway and alters immune reconstitution after UCBT.
AB  - The outcome of umbilical cord blood transplantation (UCBT) is compromised by low
      hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment,
      delayed immunological reconstitution and late memory T-cell skewing. Exposure of
      UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined
      that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in
      T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin
      (IL)-7R and IL-2Rbeta, resulting in enhanced survival mediated by the homeostatic
      cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and
      Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in
      vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES
      were elevated in the T cells of patients who received PGE2-treated UCBs.
      Consistent with the role of Wnt/beta-catenin signaling to induce and maintain
      naive, memory precursors and long-lived central memory CD8(+) cells, these
      patients also had increased fractions of CD8(+)CD45RO(-)CD62L(+) plus
      CD8(+)CD45RO(+)CD62L(+) subsets encompassing these T-cell populations. These
      effects of the PGE2/Wnt/beta-catenin axis may have significant implications for
      harnessing immunity in the context of UCBT, where impaired immune reconstitution
      is associated with late memory T-cell skewing. 

PMID- 24442209
TI  - Vaccine refrigeration: thinking outside of the box.
AB  - This commentary reviews recent changes in Centers for Disease Control (CDC)
      vaccine storage guidelines that were developed in response to an investigative
      report by the Office of the Inspector General. The use of temperature data
      loggers with probes residing in glycol vials is advised along with storing
      vaccines in pharmaceutical refrigerators. These refrigerators provide good
      thermal distribution but can warm to 8  degrees C in less than one hour after the
      power is discontinued. Consequently, electric grid instability influences
      appropriate refrigerator selection and the need for power back-up. System Average
      Interruption Duration Index (SAIDI) values quantify this instability and can be
      used to formulate region-specific guidelines. A novel aftermarket refrigerator
      with a battery back-up power supply and microprocessor control system is also
      described. 

PMID- 24442212
TI  - [A fundamental change in construction of the barley flower in the
      mutanttricomposiflora].
AB  - FollowingX-ray treatment of caryopses of the winter barley 'Dominator' a mutant
      was selected which is characterized by an extreme morphological alteration in
      flower structure. The plants do not form any reproductive organs but replace them
      by secondary flower triplets between glume and lemma. This type of ramification
      can continue to make spikeltes of the fifth order. Consequently the mutant was
      given the name "tricomposiflora" and the genetical symbol "tric" proposed. The
      type of ramification resembles a manifold composed umbel. The mutant is
      absolutely sterile and can only be propagated by heterozygous individuals.
      Further morphological alterations of the mutant compared with the original form
      are described.The genetic behaviour of the mutant was checked on heterozygous
      progenies. In theF 2-generation the mutant types occurred according to the 9:7
      (normal: mutants) segregation ratio. The genetical analysis of the following
      generations (F 3,F 4) fitted very well the assumption of a dihydbrid segregation
      pattern with two homomeric genestric 1 andtric 2.The discussion is mainly
      concerned with different types of ramification in barley induced by mutation, the
      importance of such alterations in forming new characters and their evolutionary
      significance. 

PMID- 24442211
TI  - Solid pseudopapillary tumor of the pancreas in children: surgical intervention
      strategies based on pathological findings.
AB  - PURPOSE: The appropriate surgical intervention strategies for solid
      pseudopapillary tumor (SPT) of the pancreas in children are still controversial.
      The aim of this study was to establish surgical intervention strategies based on
      the pathological findings. METHODS: We retrospectively reviewed the medical
      records of patients who underwent surgery for SPT between January 1994 and April
      2013. RESULTS: Five patients with SPT were identified. Tumors were located in the
      pancreatic head (n = 1), body (n = 2) and tail (n = 2). One patient showed
      spleen, liver and lung metastases. All five patients underwent pancreatectomy.
      Enucleation was not performed. One patient with metastases underwent partial
      hepatectomy. Four tumors had infiltration into the adjacent pancreatic
      parenchyma. The main pancreatic duct was incorporated into the tumor capsule wall
      in two patients. Surgical margins were negative in all patients without
      metastases. The median follow-up period was 37.8 months (range 7-74 months). One
      patient with metastases died at 60 months after surgery. All other patients were
      alive and showed no evidence of recurrence. CONCLUSION: Radical resection with
      negative margins should be performed for SPT. From the perspective of curability,
      we suggest that pancreatectomy is the first choice for SPT in children.

PMID- 24442213
TI  - A genetic model having complex linkage behaviour.
AB  - A genetic model is discussed in which the position and nature of equilibrium
      points for gamete frequencies depends in an unusual way on the degree of linkage
      between the loci involved. A complete mathematical analysis is made of the model:
      this is followed by a verbal discussion of the effect of linkage on such models. 

PMID- 24442210
TI  - New insights into the pathogenesis of IgA nephropathy.
AB  - IgA nephropathy (IgAN) is the most common diagnosis amongst primary glomerular
      diseases in most countries where renal biopsies are regularly performed. Only a
      fraction of these patients is at high risk of losing glomerular filtration rate
      (GFR) in particular those with high grade proteinuria, uncontrolled hypertension
      or already impaired GFR at diagnosis, and those with renal scars in the renal
      biopsy. Genetic modifiers of IgAN onset and/or course are emerging. Spontaneous
      animal models of IgAN are problematic given considerable species differences
      between the rodent and human IgA system. However, new transgenic models help to
      better understand the pathogenesis. A key pathogenetic role appears to be played
      by underglycated IgA1 as well as autoantibodies to these IgA glycoforms and IgA
      receptors such as CD89 and transferrin receptor 1. Once IgA and/or IgA-containing
      immune complexes are deposited or formed in the mesangium, secondary effector
      mechanisms become important including complement activation, release of mesangial
      growth factors (in particular platelet-derived growth factor), and finally non
      IgAN-specific events that culminate in glomerular and subsequently renal
      tubulointerstitial scaring. Here, we review these processes and describe
      potential novel therapeutic targets in IgAN. 

PMID- 24442214
TI  - [F. C. NAPP andJ. G. MENDEL a contribution to the prehistory ofMENDEL's
      experiments].
AB  - On the centenary of the death ofF. C. NAPP (22. 7. 1867), abbot of the St. Thomas
      monastery of Old-Brunn, who admittedJ. G. MENDEL in his convent, enabled him to
      study natural science and to carry out his experiments, and on the centenary of
      the election ofMENDEL to succeedNAPP as abbot (31. 3. 1868), we take note of the
      relationship between these two men as it concerns the discoveries ofMENDEL.
      Following a short biography ofNAPP we appreciate his service to agriculture and
      its basic sciences. We find a close connection between the scientific work
      ofMENDEL andNAPP in meteorology and bee keeping. 

PMID- 24442215
TI  - [The dependency of oenothera capsule maturation on the genetic constitution of
      the mother plants].
AB  - 1. The capsules of Oenothera species mature at differentrates, depending on their
      genetic constitution. 2. Even a minor change in the genome complex might be
      effective; the capsules of the B.lt, for instance, mature faster than those of
      B.lT. 3. An influence of the cytoplasm and also of the plastids on maturation
      could clearly be demonstrated. 

PMID- 24442216
TI  - [The plastid number as a character in potatoes].
AB  - The average number of plastids in ten pairs of guard cells is a very useful aid
      for screening haploids among tetraploid plants fromS. tuberosum x S. phureja.In
      individual seedlings the stomatal plastid number decreases from the cotyledons to
      the first leaves. From the lower to the upper part of stems there exists a
      decreasing gradient for plastid number and an increasing gradient for the number
      of stomata per leaf area unit, whereas the stomatal length does not show a
      consistent trend.In the stomata, plastid number and stomatal length are
      positively correlated.Mean numbers of plastids in guard cells increase by a
      factor below 2 (1.8-1.9) after each doubling of the chromosome number.The
      stomatal plastid numbers of 48-chromosome breeding lines and of their haploid
      progenies show a clear positive correlation. The mean plastid numbers in various
      haploid families from different mother plants display significant differences.The
      origin of the 'cytoplasm' (plasmone + plastome) fromS. demissum, S. stoloniferum,
      S. tuberosum, andigena forms ofS. tuberosum orS. spegazzinii in which the genome
      of the haploid is incorporated definitely influences the number of plastids in
      the guard cells.The stomatal numbers of plastids in 72 trisomic haploids show no
      significant deviation from the normal distribution of plastid numbers in
      haploids.Plastid number and stomatal length show a positive correlation in a
      population of 48 haploid lines and also in the same lines after doubling and
      quadrupling the chromosome number, the coefficient of regression decreasing with
      increasing ploidy level. In the above mentioned material there exists a strong
      positive correlation between the haploid and the corresponding homodiploid plants
      concerning stomatal length and the number of plastids.A comparison of the
      correlation stomatal length/plastid number at the 24-, 48- and 96-chromosome
      levels in three different genotypes reveals that some individuals are more
      sensitive to a rise in ploidy level than others and that the stomatal plastid
      number is a more reliable indicator of ploidy level than the stomatal length.We
      found some scattered polysomatic doubled stomata in leaf epidermissystems,
      stolons and tuber primordia of potatoes from various ploidy levels. The stomata
      at the border of the lamina are regularly endomitotically doubled, regardless of
      the original ploidy level.The hypothesis of a specific basic number of plastids
      for a given species, multiples of which should give origin to tissue-specific
      numbers, is criticized.High plastid numbers were negatively correlated with
      vitality. potatoes the possible correlation between plastid number in haploids
      and the direction of their original phyllotacticAs both the plastid number and
      the direction of the phyllotactic leaf spiral show some correlation with vitality
      in potatoes the possible correlation between plastid number in haploids and the
      direction of their original phyllotactic spiral was tried. The two groups with
      low and normal stomatal plastid numbers displayed almost equal distribution
      between left- and right-directed spirals; in the category with high plastid
      number, however, this relation was significantly displaced in favor of right
      spirals. It is tentatively proposed that both vitality and the direction of the
      phyllotactic spiral are governed by a common hormonal principle (pissibly auxins)
      which also influences the number of plastids. 

PMID- 24442217
TI  - [Results and conclusions from our work on breeding awnless winter barley].
AB  - A breeding program was started in Gulzow to get awnless winter barley of high
      yield. Though only awnless spring barley was used as starting material
      satisfactory winter hardiness was obtained by backcrossing several times with
      awned varieties of high resistance to cold. To obtain sufficient straw stiffness
      and a good grain quality is much more difficult.The highest yield strains showed
      little straw stiffness and it is assumed that absent awns were compensated for a
      longer culm. The importance of parental forms for the formation of various yield
      properties could be shown.The results obtained show that suitable parental
      strains, able to compensate for the assimilation of awns by other plant parts,
      have to be found by means of physiological investigations. 

PMID- 24442218
TI  - The effects of pre-pregnancy obesity on fetal cardiac functions.
AB  - Obesity is a substantial public health problem with a rapidly increasing
      prevalence in numerous industrialized nations. The objective of this study was to
      evaluate the effects of maternal pre-pregnancy obesity on fetal cardiac
      functions. We studied 55 fetuses of obese mothers and 44 fetuses of healthy
      mothers at 26-38 weeks of gestation. Cardiac functions were evaluated by M-mode,
      pulsed-wave, and tissue Doppler echocardiography. The two groups were similar in
      terms of maternal age, gravidity, parity, gestational age, estimated birth
      weight, serum lipids, and systolic-diastolic blood pressure. Fetal heart rate,
      diameters of the aortic and pulmonary valve annulus, aortic and pulmonary peak
      systolic velocities, ventricular systolic function, and cardiothoracic ratio were
      similar in the two groups. Pulsed-wave Doppler-derived E/A ratios in the mitral
      and tricuspid valves were similar in the two groups. The deceleration time of
      early mitral inflow was prolonged in the fetuses of the obese mothers. In the
      interventricular septum, left ventricle posterior wall, and right ventricle free
      wall, the E a and A a were higher, and E a/A a ratios were significantly lower in
      the study group than in the control group. The E/E a ratio was higher in the
      obese group than in the control group. The isovolumic relaxation time and the
      right and left ventricle myocardial performance indices were higher in the
      fetuses of the obese mothers than in the fetuses of the healthy mothers. We
      believe that maternal obesity has an important influence on fetal cardiac
      diastolic functions.

PMID- 24442219
TI  - Clinical course and interstage monitoring after the Norwood and hybrid procedures
      for hypoplastic left heart syndrome.
AB  - Infants with hypoplastic left heart syndrome (HLHS) are at risk for interstage
      morbidity and mortality, especially between the first and second surgical stages
      after the Norwood and hybrid procedures. This study compared the morbidity and
      mortality of patients treated by either the Norwood or the hybrid procedure for
      HLHS between the first and second stages who were undergoing interstage
      monitoring. Between October 2008 and December 2011, 26 infants (14 boys) with
      HLHS (n = 16) and other univentricular heart malformations with aortic arch
      anomaly (n = 10) were scheduled for interstage monitoring after Norwood I (n =
      12) and hybrid (n = 14) procedures. Three infants (11.5 %) died after first-stage
      palliation (one hybrid patient and two Norwood patients), and three infants (11.5
      %) died after second-stage palliation (two hybrid patients and one Norwood
      patient) (p = 0.83), all after early second-stage surgery (<90 days). The Norwood
      I and hybrid procedures did not differ in terms of overall mortality (23 %)
      (three hybrid and three Norwood patients; p = 1.00). Seven infants (26.9 %) could
      not be discharged from the hospital due to hemodynamic instability and were
      referred for early second-stage surgery (<90 days). After the first stage, the
      invasive reevaluation rate before discharge was high (53.8 %), with cardiac
      catheterizations for 8 of 14 patients after the hybrid procedure and for 6 of 12
      patients after the Norwood procedure (p = 0.69). A total of 11 reinterventions
      were performed (eight by catheter and three by surgery). Of the eight catheter
      reinterventions, five were performed for hybrid patients (p = 0.22). For 14
      infants, 89 days (range 10-177 days) of interstage monitoring were scheduled. One
      infant (3.9 %) died during the interstage monitoring. The findings showed a
      breach of the physiologic criteria for interstage monitoring in seven infants (50
      %) after 10 days (range 4-68 days) (five hybrid and two Norwood patients),
      leading to rehospitalization and catheterization for six patients (four hybrid
      and two Norwood patients), requiring interventions for two patients (patent
      arterial duct stent dilation, and atrial septal defect stenting, all for hybrid
      patients). Overall, three of the seven patients with red flag events of
      interstage monitoring were candidates for early second-stage surgery. In
      conclusion, morbidity among infants treated for HLHS remains high, either before
      or after hospital discharge, emphasizing the need of interstage monitoring
      programs. Despite retrograde aortic flow in infants with HLHS after the hybrid
      procedure, the mortality rate was comparable between the two groups. Mortality
      occurs after early second-stage surgery (<90 days).

PMID- 24442220
TI  - Patient radiation exposure in a modern, large-volume, pediatric cardiac
      catheterization laboratory.
AB  - Radiation exposure from pediatric cardiac catheterization may be substantial,
      although published estimates vary. We sought to report patient radiation dose
      across a range of diagnostic and interventional cases in a modern, high-volume
      pediatric catheterization laboratory. We retrospectively reviewed diagnostic and
      interventional cases performed in our pediatric catheterization laboratory from 1
      April 2009 to 30 September 2011 for which radiation usage data were available as
      reported by the Artis Zee((r)) (Siemens Medical Solutions) system.
      Electrophysiology cases were excluded. Radiation dose was quantified as air kerma
      dose (mGy) and dose-area product (DAP; MUGy m(2)). The DAP was converted to an
      effective dose millisievert (mSv) using the Monte Carlo method. Radiation usage
      data were available from 2,265 diagnostic and interventional cases with an
      overall median air kerma dose of 135 mGy [interquartile range (IQR) 59-433],
      median DAP of 760 MUGy m(2) (IQR 281-2,810), of which 75 % (IQR 59-90 %) was
      derived from fluoroscopy, and median effective dose of 6.2 mSv (IQR 2.7-14.1).
      Air kerma dose from a single camera >2,000 mGy occurred in 1.8 % of cases.
      Significant differences in all measures of radiation exposure existed based on
      procedural and interventional types (p = 0.0001), with interventional cases
      associated with the highest effective dose after adjusting for patient weight
      category (p < 0.001). Patient weight, age, fluoroscopy time, and proportional use
      of digital acquisition were independent predictors of exposure (p <= 0.001; R (2)
      = 0.59-0.64). In a modern, large-volume pediatric catheterization laboratory, the
      median effective dose is 6.2 mSv with a wide range of exposure based on patient-
      and procedure-specific factors. Radiation monitoring is an important component of
      a pediatric laboratory and further dose reduction strategies are warranted.

PMID- 24442222
TI  - Immunodeficiency and risk of myocardial infarction among HIV-positive individuals
      with access to care.
AB  - BACKGROUND: We sought to clarify the association of HIV infection and
      immunodeficiency on myocardial infarction (MI) risk. METHODS: We conducted a
      cohort study from 1996 to 2009 of HIV-positive (HIV) and demographically matched
      HIV-negative (HIV) Kaiser Permanente California health plan members. Rate ratios
      (RRs) were obtained from Poisson regression models comparing MI incidence rates
      between HIV (overall and stratified by recent and nadir CD4 count, and recent HIV
      RNA levels) and HIV subjects, adjusting for age, sex, calendar era,
      race/ethnicity, census-based socioeconomic status, smoking, alcohol/drug abuse,
      overweight/obesity, diabetes, hypertension, and lipid-lowering therapy. Among HIV
      subjects, we also evaluated the independent association of CD4, HIV RNA, and
      antiretroviral therapy (ART) use. RESULTS: The study population included 22,081
      HIV and 230,069 HIV subjects. The crude MI incidence rate per 100,000 person
      years was 283 and 165 for HIV and HIV subjects, respectively, with an adjusted RR
      of 1.4 [95% confidence interval (CI): 1.3 to 1.6]. Compared with HIV subjects
      (reference), MI rates were similar for HIV subjects with recent CD4 >=500 cells
      per microliter (RR = 1.18; 95% CI: 0.96 to 1.45) and those with nadir CD4 >=500
      cells per microliter (RR = 0.85; 95% CI: 0.55 to 1.33). Among HIV subjects, nadir
      CD4 was the only HIV-specific factor associated with MIs (RR per 100 cells =
      0.88; 95% CI: 0.81 to 0.96), whereas recent CD4 and HIV RNA, prior ART use, and
      duration of protease inhibitors and nonnucleoside reverse transcriptase
      inhibitors were not associated with MIs. CONCLUSION: HIV subjects with recent or
      nadir CD4 >=500 cells per microliter had similar MI rates compared with HIV
      subjects. Lower nadir CD4, in particular, seems to be independently associated
      with MIs. These results strengthen recommendations for earlier ART initiation.

PMID- 24442221
TI  - Characterization of T-cell responses to cryptic epitopes in recipients of a
      noncodon-optimized HIV-1 vaccine.
AB  - INTRODUCTION: Cryptic epitopes (CEs) can be encoded by any of the 5 alternative
      reading frames (ARFs, 2 sense and 3 antisense) of a known gene. Although CE
      responses are commonly detected during HIV-1 infection, it is not known whether
      these responses are induced after vaccination. METHODS: Using a bioinformatic
      approach, we determined that vaccines with codon-optimized HIV inserts
      significantly skewed CE sequences and are not likely to induce crossreactive
      responses to natural HIV CE. We then evaluated the CE- and protein-specific T
      cell responses using Gag, Pol, and ARF peptide pools among participants immunized
      with a non-codon optimized vaccine regimen of 2 pGA2/JS7 DNA primes followed by 2
      MVA/HIV62 Gag-Pol-Env vector boosts or 4 saline injections. RESULTS: Vaccinees
      had significantly more interferon gamma enzyme-linked immunosorbent spot
      (IFNgamma ELISpot) responses toward Gag (P = 0.003) but not toward Pol protein
      than did placebo recipients. However, CE-specific T-cell responses were low in
      magnitude, and their frequencies did not differ significantly between vaccine and
      placebo recipients. Additionally, most positive CE responses could not be mapped
      to individual peptides. After expanding responses in a cultured assay, however,
      the frequency and the median magnitude of responses to ARF peptides were
      significantly greater in vaccinees (P < 0.0001), indicating that CE-specific T
      cell responses are present but below an ex vivo assay's limit of detection.
      CONCLUSIONS: Our data demonstrate that HIV-1 vaccines currently in clinical
      trials are poorly immunogenic with regard to CE-specific T-cell responses.
      Therefore, the context of HIV-1 immunogens may need to be modified as a
      comprehensive strategy to broaden vaccine-induced T-cell responses.

PMID- 24442223
TI  - Life expectancy in the immune recovery era: the evolving scenario of the HIV
      epidemic in northern Italy.
AB  - INTRODUCTION: National cohort and intercohort studies have been set to describe
      the differences of life expectancy (LE) of HIV-infected individuals. OBJECTIVE:
      The aim of this study was to assess the impact of immune recovery (IR) on LE of
      patients with HIV undergoing combination antiretroviral therapy. METHODS: In this
      retrospective observational study, outcome measure was LE of patients with HIV
      compared with LE of northern Italian population. Group categorizations were as
      follows: patients with no immune recovery (nIR), patients with IR, patients who
      are immune maintained, and pre-highly active antiretroviral therapy (HAART) and
      post-HAART. Abridged life tables were constructed from age-specific mortality
      rates (per 1000 person years) to estimate LE from the age of 20-55 years.
      RESULTS: A total of 9671 patients, 71% men, were included. After 2005, we
      assisted to a rapid increase in the overall rate of patients attaining IR in the
      community coupled with a progressive decrease of AIDS death, but not of non-AIDS
      deaths. In a 40-year-old patient, LE was 38.10 years [standard error (SE) =
      2.60], 30.08 years (SE = 0.98), and 22.9 (SE = 0.69) in the IR, post-HAART group
      and nIR, respectively, compared with 41.38 years of the general Italian
      population. An approximately 5-year gap in LE was observed in IR patients.
      DISCUSSION: We describe IR at a "community" level, related to calendar year and
      apparent 10 years after HAART introduction. HAART community IR is significantly
      influencing LE and is associated with the changing clinical picture of HIV
      disease. An increasing gradient of LE exists between nIR, post-HAART, and IR
      groups, with the latter, above the age of 40 years only, reaching LE of general
      population.

PMID- 24442224
TI  - Impact of HIV exposure on health outcomes in HIV-negative infants born to HIV
      positive mothers in Sub-Saharan Africa.
AB  - BACKGROUND: Up to 30% of infants may be HIV-exposed noninfected (ENI) in
      countries with high HIV prevalence, but the impact of maternal HIV on the child's
      health remains unclear. METHODS: One hundred fifty-eight HIV ENI and 160
      unexposed (UE) Mozambican infants were evaluated at 1, 3, 9, and 12 months
      postdelivery. At each visit, a questionnaire was administered, and HIV DNA
      polymerase chain reaction and hematologic and CD4/CD8 determinations were
      measured. Linear mixed models were used to evaluate differences in hematologic
      parameters and T-cell counts between the study groups. All outpatient visits and
      admissions were registered. ENI infants received cotrimoxazol prophylaxis (CTXP).
      Negative binomial regression models were estimated to compare incidence rates of
      outpatient visits and admissions. RESULTS: Hematocrit was lower in ENI than in UE
      infants at 1, 3, and 9 months of age (P = 0.024, 0.025, and 0.012, respectively).
      Percentage of CD4 T cells was 3% lower (95% confidence interval: 0.86 to 5.15; P
      = 0.006) and percentage of CD8 T cells 1.15 times higher (95% confidence
      interval: 1.06 to 1.25; P = 0.001) in ENI vs. UE infants. ENI infants had a lower
      weight-for-age Z score (P = 0.049) but reduced incidence of outpatient visits,
      overall (P = 0.042), diarrhea (P = 0.001), and respiratory conditions (P =
      0.042). CONCLUSIONS: ENI children were more frequently anemic, had poorer
      nutritional status, and alterations in some immunologic profiles compared with UE
      children. CTXP may explain their reduced mild morbidity. These findings may
      reinforce continuation of CTXP and the need to understand the consequences of
      maternal HIV exposure in this vulnerable group of children.

PMID- 24442225
TI  - The veterans aging cohort study index is associated with concurrent risk for
      neurocognitive impairment.
AB  - OBJECTIVE: The Veterans Aging Cohort Study (VACS) Index is predictive of
      mortality and combines age, traditional HIV biomarkers (HIV-1 plasma RNA and
      current CD4 count), and non-HIV biomarkers (indicators of renal and liver
      function, anemia, and hepatitis C coinfection). We examined the association
      between the VACS Index and HIV-associated neurocognitive impairment (NCI). DESIGN
      AND METHODS: Participants included 601 HIV-infected adults enrolled in cohort
      studies at the University of California, San Diego, HIV Neurobehavioral Research
      Program (ages: 18-76 years; 88% male; 63% white; median current CD4 = 364
      cells/mm; 63% on antiretroviral therapy; AIDS = 64%). Biomarkers used in
      calculating the VACS Index were measured in prospectively collected blood samples
      using conventional laboratory methods. NCI was defined using global and seven
      domain deficit scores. RESULTS: Higher VACS Index scores were associated with
      concurrent risk for global NCI [P < 0.001; odds ratio = 1.21, confidence interval
      (CI): 1.12 to 1.32], even when adjusting for psychiatric comorbidities. This
      relation was statistically significant for most cognitive domains in adjusted
      models. Furthermore, the VACS Index predicted concurrent NCI beyond nadir CD4 and
      estimated duration of infection. Older age, lower hemoglobin, and lower CD4
      counts were the VACS components most strongly linked to NCI. CONCLUSIONS: The
      findings extend previous research on the potential usefulness of the VACS Index
      in predicting HIV-associated outcomes to include NCI. Although the effect size
      was relatively small, our findings suggest that demographic information, HIV
      disease factors, and common comorbidities might each play important roles in the
      clinical manifestation of cognitive impairment among HIV-infected individuals.
      Additional research is needed to determine if a more sensitive and specific index
      can be developed.

PMID- 24442226
TI  - A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA
      concentrations of antiretroviral-naive HIV-1-infected women.
AB  - BACKGROUND: In HIV-1-infected women, CD4 count declines occur during pregnancy,
      which has been attributed to hemodilution. However, for women who have not
      initiated antiretroviral therapy, it is unclear if CD4 declines are sustained
      beyond pregnancy and accompanied by increased viral levels, which could indicate
      an effect of pregnancy on accelerating HIV-1 disease progression. METHODS: In a
      prospective study among 2269 HIV-1-infected antiretroviral therapy-naive women
      from 7 African countries, we examined the effect of pregnancy on HIV-1 disease
      progression. We used linear mixed models to compare CD4 counts and plasma HIV-1
      RNA concentrations between pregnant, postpartum, and nonpregnant periods.
      RESULTS: Women contributed 3270 person-years of follow-up, during which time 476
      women became pregnant. In adjusted analysis, CD4 counts were an average of 56
      (95% confidence interval: 39 to 73) cells/mm lower during pregnant compared with
      nonpregnant periods and 70 (95% confidence interval: 53 to 88) cells/mm lower
      during pregnant compared with postpartum periods; these results were consistent
      when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA
      concentrations were not different between pregnant and nonpregnant periods (P =
      0.9) or pregnant and postpartum periods (P = 0.3). Neither CD4 counts nor plasma
      HIV-1 RNA levels were significantly different in postpartum compared with
      nonpregnant periods. CONCLUSIONS: CD4 count declines among HIV-1-infected women
      during pregnancy are temporary and not sustained in postpartum periods. Pregnancy
      does not have a short-term impact on plasma HIV-1 RNA concentrations.

PMID- 24442227
TI  - Management of rheumatic heart disease in uganda: the emerging epidemic of non
      AIDS comorbidity in resource-limited settings.

PMID- 24442228
TI  - Diagnostic criteria schemes for multicentric Castleman disease in 75 cases.

PMID- 24442229
TI  - Short-term effectiveness and safety of third-line antiretroviral regimens among
      patients in Western India.

PMID- 24442230
TI  - Characteristics of patients on antiretroviral therapy with prolonged virological
      failure.

PMID- 24442231
TI  - Opinions and attitudes of participants in a randomized controlled trial examining
      the efficacy of SMS reminders to enhance antiretroviral adherence: a cross
      sectional survey.

PMID- 24442232
TI  - cART reverses hyposplenism in HIV-1 infection.

PMID- 24442233
TI  - Unreported antiretroviral use by HIV-1-infected participants enrolling in a
      prospective research study.

PMID- 24442235
TI  - Conformational transitions in the Ramachandran space of amino acids using the
      dynamic rotational isomeric state (DRIS) model.
AB  - The dynamic rotational isomeric state model is applied to predict the internal
      dynamics of the 20 amino acids. Transition rates between rotational isomeric
      states are calculated from molecular dynamics simulations of Gly-Gly-X-Gly-Gly
      peptides where X represents one of the 20 amino acids. Predicted relaxation times
      are in good agreement with fluorescence quenching rate measurements. 

PMID- 24442234
TI  - Single-molecule FRET supports the two-state model of Argonaute action.
AB  - Argonaute can be found in all three domains of life and is the functional core of
      the eukaryotic RNA-silencing machinery. In order to shed light on the
      conformational changes that drive Argonaute action, we performed single-molecule
      FRET measurements employing a so far uncharacterized member of the Argonaute
      family, namely Argonaute from the archaeal organism Methanocaldococcus jannaschii
      (MjAgo). We show that MjAgo is a catalytically active Argonaute variant
      hydrolyzing exclusively DNA target strands out of a DNA/DNA hybrid. We studied
      the interplay between Argonaute and nucleic acids using fluorescent dyes
      covalently attached at different positions of the DNA guide as steric reporters.
      This allowed us to determine structurally confined parts of the protein scaffold
      and flexible regions of the DNA guide. Single-molecule FRET measurements
      demonstrate that the 3'end of the DNA guide is released from the PAZ domain upon
      target strand loading. This conformational change does not necessitate target
      strand cleavage but a fully complementary target strand. Thus, our data support
      the two state model for Argonaute action. 

PMID- 24442236
TI  - BVES inhibition triggers epithelial-mesenchymal transition in human
      hepatocellular carcinoma.
AB  - BACKGROUND/AIM: Metastasis contributes to the poor prognosis of hepatocellular
      carcinoma (HCC). However, the mechanism through which a primary HCC cell develops
      into a metastatic phenotype is not well understood. In this study, we set out to
      elucidate how blood vessel epicardial substance (BVES), a novel adhesion molecule
      regulating tight junction formation, mediates invasion and metastasis in human
      HCC cells. METHODS: qRT-PCR, western blot and IHC were used to detect the
      expression of BVES in HCC samples and HCC cell lines. Small interfering RNAs
      (siRNAs) against human BVES were synthesized and used to transfect Huh7 cells.
      Then, the interference efficiency and the expression of mesenchymal marker
      vimentin and epithelial marker E-cadherin were measured by qRT-PCR and western
      blot. F-actin cytoskeleton was detected using TRITC-conjugated phalloidin. After
      inhibition of BVES, wound healing experiment and transwell assay were used to
      analyze the migratory and invasive ability of Huh7 cells. RESULTS: BVES was down
      regulated in human HCC tissues and HCC cell lines with high metastatic potential.
      After BVES inhibition, Huh7 cells exhibited some morphological changes including
      cytoskeleton rearrangement and junctional disruption. Cell migration and invasion
      were increased concomitant with increased expression of vimentin, IL-6, MMP2,
      MMP9 and decreased expression of E-cadherin. Finally, we found the expression of
      epithelial-mesenchymal transition (EMT) transcription factors Snail1 and Twist1
      was significantly increased in BVES knockdown cells. CONCLUSIONS: Our results
      suggest that down-regulation of BVES in HCC induces EMT, thus promoting invasion
      and metastasis in HCC cells.

PMID- 24442237
TI  - Netrin-1 induces epithelial-mesenchymal transition and promotes hepatocellular
      carcinoma invasiveness.
AB  - BACKGROUND: Hypoxia is often found in solid tumors and is associated with tumor
      progression and poor clinical outcomes. We elucidated the mechanism by which
      netrin-1 released under hypoxic stress can induce epithelial-mesenchymal
      transition (EMT) to promote invasion in hepatocellular carcinoma (HCC) cells.
      METHODS: The expression of netrin-1 and the dependent receptors UNC5H and deleted
      in colorectal cancer (DCC) in HCC was examined by immunohistochemistry or western
      blot. The HepG2 cells were cultured in 21% O2 (normoxia) or 1% O2 (hypoxia) for
      24 h. The release of netrin-1 from hypoxic cells was detected by ELISA.
      Expression of E-cadherin and vimentin were examined by western blot. Inverted
      microscopy or confocal microscopy was used to show the cell morphology or
      cytoskeletal rearrangements. Cell invasion induced by hypoxia was analyzed by
      Transwell chamber. Cytokine IL-8 and IL-10 mRNA levels were assessed by real-time
      PCR. RESULTS: The expression of netrin-1 was increased in HCC tissue and cell
      lines. The dependent receptors UNC5H and DCC were decreased in most HCC cell
      lines. Hypoxia induced netrin-1 release in a time-dependent manner. EMT induction
      was found to occur in hypoxic HCC cells in a process that was dependent on the
      extracellular release of netrin-1. Moreover, overexpression of netrin-1 resulted
      in EMT induction in normoxic tumor cells. Cytoskeletal rearrangements were found
      to occur and cell invasion was increased in cells with netrin-1 overexpression.
      Lastly, mRNA of IL-8 and IL-10 were also increased after recombinant human netrin
      1 treatment. CONCLUSION: These results suggest that in hypoxic HCC cells, netrin
      1 activates downstream signaling pathways to induce EMT activation with
      subsequent production of multiple inflammatory mediators which in turn promotes
      cancer invasion.

PMID- 24442238
TI  - Regulatory role of CD4(+)CD25 (+)Foxp3 (+) regulatory T cells on IL-17-secreting
      T cells in chronic hepatitis B patients.
AB  - BACKGROUND: Both interleukin (IL)-17-secreting CD4(+) T (Th17) and
      CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells have been shown to be associated
      with disease progression or liver damage in chronic hepatitis B (CHB) patients.
      However, the relationship between Treg cells and IL-17-secreting T cells in
      hepatitis B virus (HBV) infections is unclear. METHODS: The frequencies of Treg
      cells and IL-17-secreting T cells in hepatitis B e antigen (HBeAg)-positive CHB
      patients and healthy subjects were measured by flow cytometric analysis. The role
      of Treg cells on the differentiation of Ag-specific IL-17-secreting T cells was
      determined by removing the Treg cells from peripheral blood mononuclear cells
      (PBMCs) in HBeAg-positive CHB patients. RESULTS: The frequencies of both Th17
      (1.71 +/- 0.58 vs. 1.08 +/- 0.36 %; P < 0.01) and Treg cells (8.92 +/- 4.11 vs.
      6.45 +/- 1.56 %; P < 0.01) were increased in the peripheral blood of HBeAg
      positive CHB patients compared with healthy controls, but in not the IL-17
      secreting CD8(+) T (Tc17) cells. The frequency of Treg cells was significantly
      associated with that of Th17 cells (r = 0.625, P = 0.001) in CHB patients.
      Spearman analysis showed a positive correlation between the frequency of Treg
      cells and HBV DNA load (r = 0.508, P = 0.008), as well as between the frequency
      of Th17 cells and serum alanine aminotransferase level (r = 0.516, P = 0.007).
      The deletion of Treg cells significantly enhanced both Th17 and Tc17 cell
      development in PBMCs following recombinant HBV core antigen stimulation.
      CONCLUSIONS: Our data indicate a clear inverse relationship between Th17 cells
      and Treg cells and that Treg cells can inhibit Th17 cell development in CHB
      patients.

PMID- 24442239
TI  - In silico approach for the identification of immunological properties of enolase
      from Trypanosoma cruzi and its possible usefulness as vaccine in Chagas disease.
AB  - Nowadays, Chagas disease is a major health problem in Latin America that has been
      disseminated also into non-endemic countries. Currently, a vaccine against Chagas
      disease does not exist. In the present study, the gene encoding Trypanosoma cruzi
      enolase (TcENO) was amplified, cloned, and sequenced and the recombinant protein
      was purified. We used in silico and an experimental assay to investigate the
      immunological role of TcENO. The in silico assays showed that TcENO sequence
      contains characteristic motifs of enolase; additionally, a transmembranal region
      was identified, and this could indicate the potential membrane localization of
      TcENO. Moreover, both B lymphocyte and cytotoxic T lymphocytes (CTL) predicted
      epitopes were localized; these results suggest the possibility that TcENO can
      develop both humoral and cellular immune responses. Furthermore, the presence of
      antibodies was verified by western blot assays, showing that the purified
      recombinant protein was detected by sera from experimentally infected mice and
      sera of patients with Chagas disease. These results indicate that TcENO is
      immunogenic and could be used as a vaccine candidate. 

PMID- 24442240
TI  - Meta-analysis indicates lack of local adaptation of Schistosoma mansoni to
      Biomphalaria alexandrina in Egypt.
AB  - In Egypt, reclaiming portions of the desert using water from the Nile has
      resulted in large-scale invasion of Biomphalaria alexandrina in these regions.
      Studies exploring the local adaptation of Schistosoma mansoni to its snail host
      have been carried out to predict the extension of schistosomiasis to newly
      reclaimed areas. A meta-analysis of the relevant reports was conducted to compare
      the different biological characteristics of sympatric and allopatric Schistosoma
      mansoni and Biomphalaria alexandrina using different experimental designs. The
      results showed that there were no significant differences in the biological
      characteristics of sympatric and allopatric populations. The experimental design
      of some of the studies analyzed was found to affect the total cercarial
      production. The distance between the origin of the parasite and that of the snail
      did not affect any of the biological characteristics. The results showed that
      there is no evidence of local adaptation between Schistosoma mansoni and
      Biomphalaria alexandrina; however, the parasite is adapted to its intermediate
      host throughout the water bodies located in Egypt. The absence of local
      adaptation between Schistosoma mansoni and Biomphalaria alexandrina is likely of
      critical importance in predicting public health risks engendered by future
      reclaimed agriculture projects. Indeed, these results could assist in determining
      the appropriate balance between the development of water resource projects and
      schistosomiasis control in Egypt. 

PMID- 24442242
TI  - Vertebral rotation in adolescent idiopathic scoliosis calculated by radiograph
      and back surface analysis-based methods: correlation between the Raimondi method
      and rasterstereography. Eur Spine J;22:2336-2337 : Statistical perspectives part
      II.

PMID- 24442241
TI  - Set5 and Set1 cooperate to repress gene expression at telomeres and
      retrotransposons.
AB  - A complex interplay between multiple chromatin modifiers is critical for cells to
      regulate chromatin structure and accessibility during essential DNA-templated
      processes such as transcription. However, the coordinated activities of these
      chromatin modifiers in the regulation of gene expression are not fully
      understood. We previously determined that the budding yeast histone H4
      methyltransferase Set5 functions together with Set1, the H3K4 methyltransferase,
      in specific cellular contexts. Here, we sought to understand the relationship
      between these evolutionarily conserved enzymes in the regulation of gene
      expression. We generated a comprehensive genetic interaction map of the
      functionally uncharacterized Set5 methyltransferase and expanded the existing
      genetic interactome of the global chromatin modifier Set1, revealing functional
      overlap of the two enzymes in chromatin-related networks, such as transcription.
      Furthermore, gene expression profiling via RNA-Seq revealed an unexpected
      synergistic role of Set1 and Set5 in repressing transcription of Ty transposable
      elements and genes located in subtelomeric regions. This study uncovers novel
      pathways in which the methyltransferase Set5 participates and, more importantly,
      reveals a partnership between Set1 and Set5 in transcriptional repression near
      repetitive DNA elements in budding yeast. Together, our results define a new
      functional relationship between histone H3 and H4 methyltransferases, whose
      combined activity may be implicated in preserving genomic integrity. 

PMID- 24442243
TI  - The influence of visual feedback on the mental representation of gait in patients
      with THR: a new approach for an experimental rehabilitation strategy.
AB  - Due to total hip replacement (THR), patients reveal abnormal gait patterns which
      post-operative do often not return to "normal". The restoration towards normal
      gait reduces stress on the adjacent joints which consequently reduces risk of
      osteoarthrosis development. Motor-performance is related to the structure of the
      movement in long-term memory, thus it seems to be essential to imprint correct
      gait patterns in there. Mental representation structures can develop over the
      course of training and visual feedback presumably helps regaining a better
      representation of gait in long-term memory. The purpose of this study is to
      evaluate the effect of visual feedback on mental representation in patients with
      THR. In a randomized controlled trial, 20 women (57 +/- 6 years) with THR have
      been enrolled. Subjects were randomly assigned to a control group (CG) or
      intervention group (IG). Additionally to inpatient treatment, all subjects
      participated in a standardized gait training including either an intervention
      based on verbal information from a physiotherapist (CG) or an intervention based
      on real-time visual feedback (IG). Mental representation was measured in pre-test
      and post-test using the structure-dimensional analysis. Results indicate
      significant improvements in mental representation of gait in the post-test only
      in IG, suggesting that beneficial effects were provoked by visual feedback.

PMID- 24442245
TI  - Late effects in children treated with intensive multimodal therapy for high-risk
      neuroblastoma: high incidence of endocrine and growth problems.
AB  - Due to the poor prognosis of high-risk (HR) neuroblastoma (NBL), scant data exist
      on late effects after treatment. Recently, protocols utilizing intense multimodal
      treatment have resulted in improved long-term survival. The objective of this
      study was to determine the prevalence of late effects in survivors of HR NBL. A
      retrospective review of clinical data for serial patients completing treatment
      between September 1994 and October 2007 and surviving for at least 1 year was
      performed. Therapy included aggressive chemotherapy, surgery, radiation and
      single or tandem SCT. Oncology follow-up was standard; clinical criteria were
      utilized for referrals to endocrinology and other services. Fifty-one eligible
      patients were identified. Median follow-up was 6.1 years (range 1.0-15.2). Height
      was significantly impacted (DeltaZ-score -1.91 in those treated with TBI and 
      0.77 in those without). Pre-diabetes or diabetes, hypothyroidism and ovarian
      insufficiency were observed in 50, 59 and 75% of at-risk survivors, respectively.
      Hearing loss and dental issues were common. Nine patients had relapse of NBL;
      seven died of progressive disease. As there is a high prevalence of late effects
      in long-term survivors of HR NBL, close monitoring and further studies after
      treatment are indicated, and in particular after more modern, non-TBI regimens. 

PMID- 24442244
TI  - Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and
      R-FC in CLL at diagnosis.
AB  - The importance of early therapy intensification in B-cell CLL (B-CLL) patients
      remains to be defined. Even though several studies have been published, no
      randomized trials comparing directly autologous stem cell transplant (ASCT) and
      the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC)
      have been reported so far. To assess the benefit of a first-line aggressive
      therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and
      high-dose chemotherapy supported by ASCT in patients under 65 years of age, with
      stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48
      in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms
      were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in
      the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and
      overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the
      first time in a randomized manner, that frontline ASCT does not translate into a
      survival advantage when compared with benchmark chemoimmunotherapy in B-CLL
      patients; the possibility of its clinical benefit in certain subgroups remains
      uncertain. 

PMID- 24442246
TI  - Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell
      transplantation: a not-so-good cancer after all!
AB  - Hodgkin lymphoma (HL) relapsing after an autologous hematopoietic cell transplant
      (HCT) poses a therapeutic challenge. In this setting, salvage chemotherapy (for
      example, gemcitabine-based, ifosfamide-containing and others) or immunotherapy
      (for example, brentuximab vedotin) is essential as a bridging-cytoreduction
      strategy to an allogeneic HCT. Myeloablative allogeneic hematopoietic cell
      transplantation in relapsed HL is associated with high rates of non-relapse
      mortality. In carefully selected patients with chemosensitive disease,
      allografting following lower-intensity conditioning regimens can provide durable
      disease control rates of about 25-35%. Promising early results with
      haploidentical and umbilical cord transplantation are noteworthy and are
      expanding this procedure to patients for whom HLA-matched related or unrelated
      donors are not available. Unfortunately, a significant number of HL patients
      relapsing after an autologous HCT are not candidates for allografting because of
      the presence of resistant disease, donor unavailability or comorbidities.
      Brentuximab vedotin is approved for HL relapsing after a prior autograft.
      Rituximab and bendamustine are also active in this setting, albeit with short
      durations of remission. Histone deacetylase inhibitors (for example,
      panobinostat, mocetinostat), mTOR inhibitors (for example, everolimus) and
      immunomodulatory agents (lenalidomide) have shown activity in phase II trials,
      but currently are not approved for this indication. Second autologous HCT are
      rarely performed but this approach should not be considered standard practice at
      this time. The need for effective agents for post autograft failures of HL
      largely remains unmet. Continuous efforts to ensure early referral of such
      patients for allogeneic HCT or investigational therapies are the key to improving
      outcomes of this not-so-good lymphoma. 

PMID- 24442247
TI  - High prevalence of distress in patients after allogeneic hematopoietic SCT: fear
      of progression is associated with a younger age.
AB  - Little is known about the psychological burden patients are left with after
      successful allogeneic hematopoietic SCT (HSCT). With the main focus on physical
      condition and common transplant complications, psychological symptoms often
      remain neglected in daily practice. To assess the prevalence of distress in
      patients who have undergone allogeneic HSCT, we conducted a cross-sectional pilot
      study in 50 consecutive patients from our outpatient transplant clinic using
      standardized questionnaires. Distress was categorized by symptoms of anxiety,
      fear of progression, depression and post-traumatic stress disorder (PTSD). Forty
      one patients completed self-administered questionnaires. The median age was 53
      years (21-74 years) and the mean time after transplantation was 614 days (25-2070
      days). In total, 18 patients (44%) showed symptoms of distress. Among these 18
      patients, 11 patients reported symptoms of anxiety, 12 patients suffered from
      fear of progression, 11 patients showed symptoms of depression and 6 patients of
      PTSD. Age below 55 years was significantly associated with fear of progression
      (P=0.004). This study demonstrates the high prevalence of distress in patients
      who have undergone allogeneic HSCT. Our results suggest an unmet need for
      professional support and intervention. These findings may be relevant as distress
      could have an influence on the outcome after HSCT. 

PMID- 24442248
TI  - Rituximab as a treatment for factor VIII inhibitor in a patient with chronic
      GVHD.

PMID- 24442249
TI  - Alopecia areata after HLA-identical BMT from an affected, sibling donor.

PMID- 24442250
TI  - Conditioning regimens in allo-SCT for thalassemia major.
AB  - Allogeneic hematopoietic SCT remains the only treatment that can correct the
      hematological manifestations in patients with thalassemia major. Improving the
      clinical outcomes of high-risk, heavily transfused patients with liver fibrosis
      and inadequate iron chelation remains a challenge. Because of the relatively high
      probability of graft rejection and regimen-related toxicity in many patients
      receiving SCT for advanced thalassemia major, further development of new
      treatment regimens is warranted. This review addresses the reported clinical
      studies in patients with advanced thalassemia major and we have summarized our
      suggested conditioning approach to improve the outcome after SCT. 

PMID- 24442251
TI  - Development of cellulitis caused by Aeromonas hydrophila in allogeneic
      hematopoietic transplantation: a case report.

PMID- 24442252
TI  - Health-related quality of life of patients with newly diagnosed chronic myeloid
      leukemia treated with allogeneic hematopoietic SCT versus imatinib.
AB  - To evaluate and compare the health-related quality of life (HRQOL) of patients
      with newly diagnosed CML in the first chronic phase (CML-CP1) receiving HLA
      identical sibling donor (ISD) hematopoietic SCT (HSCT) or imatinib, a cross
      sectional study that was part of a prospective cohort study at the Institute of
      Hematology, Peking University was performed. A total of 222 patients including
      126 and 96 in the imatinib and ISD HSCT groups, respectively, were enrolled.
      HRQOL was measured using the Medical Outcomes Study 36-Item Short-Form Health
      Survey. The ISD HSCT group functioned significantly better on the role-physical
      functioning and mental health subscales, as well as the mental component summary
      (MCS) than the imatinib group. HRQOL was generally comparable to groups in the
      young population. Multivariate analysis showed that white blood cell count >= 30
      * 10(9)/L and plts count >= 450 * 10(9)/L were the major adverse factors
      affecting HRQOL in long-term survivors. Imatinib therapy was also an adverse
      factor affecting the MCS (odds ratio=1.7, P=0.032). Thus, long-term CML-CP1
      survivors receiving ISD HSCT can attain desirable HRQOL comparable to or better
      than that of patients receiving imatinib.

PMID- 24442254
TI  - Rhodamine-based fluorescent off-on sensor for Fe3+--in aqueous solution and in
      living cells: 8-aminoquinoline receptor and 2:1 binding.
AB  - 8-Aminoquinoline (8-AQ) and 2-aminopyridine (AmPyr) both as ionophoric agents
      were robustly used in development of a cation sensor. To evaluate the effect of
      complexation with cations, flexible 2-aminopyridine and rigid 8-AQ moiety were
      directly introduced into rhodamine chromophore and two candidate fluorescent
      sensors were constructed successfully. Rh-AQ with a rigid 8-AQ fragment exhibited
      turn-on fluorescence and color responses to Fe(3+) ion over other metal ions
      related to biology in aqueous solution. The sensor Rh-AmPyr with a flexible 2
      aminopyridine did not give positive responses to cations although with a similar
      binding cavity as on Rh-AQ. Furthermore, the 2:1 recognition mode of Rh-AQ with
      Fe(3+) was proved according to the 1D and 2D COSY H-H NMR experiments. The live
      cell imaging experiments demonstrated that Rh-AQ could be successfully applied as
      a bioimaging agent for monitoring Fe(3+) in living cells.

PMID- 24442253
TI  - Splenectomy as a measure to treat prolonged post-transplant cytopenia associated
      with hypersplenism.

PMID- 24442255
TI  - Production of poly-3-(hydroxybutyrate-co-hydroxyvalerate) by Haloferax
      mediterranei using rice-based ethanol stillage with simultaneous recovery and re
      use of medium salts.
AB  - Haloferax mediterranei holds promise for competitive industrial-scale production
      of polyhydroxyalkanoate (PHA) because cheap carbon sources can be used thus
      lowering production costs. Although high salt concentration in production medium
      permits a non-sterile, low-cost process, salt disposal after process completion
      is a problem as current environmental standards do not allow total dissolved
      solids (TDS) above 2000 mg/l in discharge water. As the first objective of this
      work, the waste product of rice-based ethanol industry, stillage, was used for
      the production of PHA by H. mediterranei in shake flasks. Utilization of raw
      stillage led to 71 +/- 2% (of dry cell weight) PHA accumulation and 16.42 +/-
      0.02 g/l PHA production. The product yield coefficient was 0.35 while 0.17 g/l h
      volumetric productivity was attained. Simultaneous reduction of BOD5 and COD
      values of stillage by 83% was accomplished. The PHA was isolated by osmotic lysis
      of cells, purification by sodium dodecyl sulfate and organic solvents. The
      biopolymer was identified as poly-3-(hydroxybutyrate-co-15.4 mol%
      hydroxyvalerate) (PHBV). This first report on utilization of rice-based ethanol
      stillage for PHBV production by H. mediterranei is currently the most cost
      effective. As the second objective, directional properties of decanoic acid
      together with temperature dependence of water solubility in decanoic acid were
      applied for two-stage desalination of the spent stillage medium. We report for
      the first time, recovery and re-use of 96% of the medium salts for PHA production
      thus removing the major bottleneck in the potential application of H.
      mediterranei for industrial production of PHBV. Final discharge water had TDS
      content of 670 mg/l.

PMID- 24442256
TI  - Aspartic acid as an internal CO2 reservoir in Zea mays: Effect of oxygen
      concentration and of far-red illumination.
AB  - By placing leaf segments first in CO2 in the dark, then in pure nitrogen either
      in the dark and afterwards in the light or immediately in the light, the
      existence of internal CO2 pools which can be used for photosynthesis had been
      demonstrated. In Zea mays L. there are two such pools: one which in the absence
      of any energy source is short-lived (t1/2 ca. 2 min), and another which is
      relatively long-lived (t1/2 ca. 50 min).Under different oxygen concentrations the
      level of the short-lived CO2 pool exibited a parallel variation with the level of
      aspartic acid. Only a fraction of the total aspartic acid (60%) constituted the
      active pool, the quantity of which was equal to the short-lived CO2. In the
      absence of O2 but under far-red irradiation (maximum 740 nm), a net synthesis of
      aspartic acid was observed; its extent depended on the intensity of the light.The
      similarity in the response to O2 and to long-wavelength irradiation suggests that
      aspartate synthesis is regulated by ATP, the high-energy compound common to both
      oxidative and cyclic phosphorylations. The formation of aspartic acid observed in
      the dark under N2+1% CO2 immediately following illumination under pure N2
      suggests use of ATP accumulated in the preceding light period, in aspartate
      synthesis.Even though Zea mays is predominantly a "malate former", it appears
      that aspartate must also be considered as a readily available donor of CO2 since,
      when aspartate is present, O2 release is always immediate while, when it is not,
      O2 release is delayed. 

PMID- 24442257
TI  - Carrier-mediated auxin transport.
AB  - 1. Auxin (IAA) transport was investigated using crown gall suspension tissue
      culture cells. We have shown that auxin can cross the plasmalemma both by
      transport of IAA anions on a saturable carrier and by passive (not
      carriermediated) diffusion of the lipid-soluble undissociated IAA molecules
      (pK=4.7). The pH optimum of the carrier for auxin influx is about pH 6 and it is
      half-saturated by auxin concentrations in the region of 1-5 MUM. We found that
      the synthetic auxin 2,4D specifically inhibited carrier-mediated IAA anion
      influx, and possibly also efflux. Other lipid-soluble weak acids which are not
      auxins, such as 3,4-dichlorobenzoic acid, had no effect on auxin transport. By
      contrast, we found that TIBA, an inhibitor of polar auxin transport in intact
      tissues inhibited only the carrier-mediated efflux of IAA. 2. When the pH outside
      the cells is maintained below that of the cytoplasm (pH 7), auxin can be
      accumulated by the cells: In the initial phase of uptake, the direction of the
      auxin concentration gradient allows both passive carrier-mediated anion influx
      (inhibited by 2,4D) and a passive diffusion of undissociated acid molecules into
      the cells. Once inside the cytoplasm, the undissociated molecules ionise,
      producing IAA anions, to a greater extent than in the more acidic extracellular
      environment. Uptake by passive diffusion continues as long as the extracellular
      concentration of undissociated acid remains higher than its intra-cellular
      concentration. Thus, the direction of the auxin anion concentration gradient is
      reversed after a short period of uptake and auxin accumulates within the cells.
      The carrier is now able to mediate passive IAA anion efflux (inhibited by TIBA)
      down this concentration gradient even though net uptake still proceeds because
      the carrier is saturable whereas passive diffusion is not. 3. Auxin "secretion"
      from cells is regarded as a critical step in polar auxin transport. The evidence
      which we present is consistent with the view that auxin "secretion" depends on a
      passive carrier-mediated efflux of auxin anions which accumulate within the cells
      when the extra-cellular pH is below that of the cytoplasm. The implications of
      this view for theories of polar auxin transport are discussed. 

PMID- 24442258
TI  - Qualitative and quantitative analyses of gibberellins throughout seed maturation
      in Pisum sativum cv. Progress No. 9.
AB  - In addition to the previously identified GA20 and GA29 in immature seeds of Pisum
      sativum L. cv. Progress No. 9, GA9, GA17, GA38, GA44, abscisic acid and
      dihydrophaseic acid have been identified. The levels of GA9, GA17, GA20 and GA29
      have been determined throughout seed maturation by GC-MS. GA20 and GA29 are the
      major gibberellins in terms of quantity, the other gibberellins remain at very
      low levels throughout development of the seed. 

PMID- 24442259
TI  - A procedure for the in vivo determination of enzyme activity in higher plant
      tissue.
AB  - Rapid freezing of higher plant tissue in liquid nitrogen renders the cells
      permeable to a wide range of substrate molecules. Tissue permeabilized by
      repeated freeze-thaw treatment can be used for the measurement of several
      enzymes. With most of the tissues examined maximum in vivo activities were
      obtained using a combination of freeze-thaw treatment followed by vacuum
      infiltration. The activities and properties of enzymes determined with this
      procedure are very comparable with those obtained for enzymes prepared by
      conventional extraction procedures. 

PMID- 24442260
TI  - Fluxes and compartmentation of potassium and chloride in the green alga
      Mougeotia.
AB  - Some ionic relations of the filamentous green alga Mougeotia sp. have been
      analyzed under different light conditions. Data from influx and efflux
      measurements using (86)Rb(+) and (36)Cl(-) fit the model of three cellular
      compartments (cell wall, cytoplasm, vacuole) in series. This result is
      remarkable, since in a Mougeotia cell at least two thirds of the cytoplasmic
      compartment are occupied by the cell-filling, flat and nearly rectangular
      chloroplast which is axially oriented. The chloroplast is concluded to be part of
      the cytoplasmic flux compartment.Photosynthetically saturating irradiances of
      continuous white light enhance the active and passive fluxes of K(+) and Cl(-) at
      the plasmalemma by a factor of 3. Photosystem II is responsible for the light
      dependent increase of the uptake of Cl(-) ((36)Cl(-)) whereas the uptake of K(+)
      ((86)Rb(+)) depends additionally on energy from photosystem I.Ion flux
      measurements performed after irradiations with red and far-red, respectively,
      show that the fluxes of K(+) and Cl(-) across the plasmalemma are not affected by
      the state of phytochrome. 

PMID- 24442261
TI  - Investigation of some enzymatic activities contributing to the biosynthesis of
      galactolipid precursors in Vicia faba.
AB  - Assay conditions, intracellular distribution and change of activity during
      greening of etiolated seedlings of Vicia faba L. have been investigated for
      aldose reductase (EC 1.1.1.21), UDP-glucose pyrophosphorylase (EC 2.7.7.9), UDP
      glucose 4-epimerase (EC 5.1.3.2) and phosphatidate phosphatase (EC 3.1.3.4). The
      first three enzymes were found to be soluble proteins of the cytoplasm, whereas
      phosphatidate phosphatase was found in the soluble and a sedimentable (15000 Xg)
      fraction. 

PMID- 24442262
TI  - [Evidence of DNA-synthesis in hypocotyls and cytoledons of inhibited and non
      inhibited seedlings of Sinapis alba].
AB  - Etiolated elongating hypocotyls of Sinapis alba synthesize DNA 40-72 h after
      sowing. The increase in DNA content is about 62.5%. Four-hour pulse experiments
      showed an increasing rate of [(32)P]orthophosphate incorporation; the maximum
      rate was obtained 64-68 h after sowing. In the cotyledons DNA increase up to the
      56th h after sowing; later the DNA-content remains constant. During this time the
      incorporation of (32)P into the DNA of the cotyledons decreases
      continuously.After simultaneous application of Fluordesoxyuridin (FdUrd) (4*10(
      5)M) and thymidine (4*10(-4)M) or thymidylate (4*10(-4)M) 40-64 h after sowing,
      the growth rate was the same as that in H2O treated controls, whereas application
      of FdUrd (4*10(-5)M) alone inhibited growth.In the presence of FdUrd (4*10(-5)M)
      thymidine (4*10(-4)M) and thymidylate (4*10(-4)M) enhanced the specific activity
      of the DNA up to respectively 68% and 63% of that in the H2O treated controls.
      Hydroxyurea (4 mg/ml) inhibited DNA-synthesis and growth in the same manner as
      FdUrd.The prolonged DNA-synthesis and the reversal of the FdUrd effect by
      thymidine or thymidylate are discussed. 

PMID- 24442263
TI  - Possible spontaneous PFO closure after thrombus trapped in PFO.

PMID- 24442264
TI  - Systemic arterial endothelial function in children and young adults with
      idiopathic pulmonary arterial hypertension: is there a relation to pulmonary
      endothelium-dependent relaxation?
AB  - Pulmonary arterial endothelial function is known to be affected in patients with
      idiopathic pulmonary arterial hypertension (IPAH). Current reports also detected
      peripheral systemic arterial dysfunction in IPAH patients. The purpose of this
      study was to assess whether there is a relation between pulmonary arterial and
      systemic arterial endothelial function. Pulmonary arterial endothelium-dependent
      relaxation was assessed by changes in pulmonary blood flow in response to
      acetylcholine which were determined using intravascular Doppler flow
      measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of
      pulmonary blood flow velocity in response to acetylcholine relative to baseline
      values. Systemic arterial endothelial function was assessed by the vascular
      response to reactive hyperemia, and was recorded non-invasively by peripheral
      arterial finger tonometry under standardized conditions. Thirteen children and
      young adults [mean age 16.7 (+/-5.6) years] with IPAH and 13 age-/gender-matched
      controls were included in the study. Digital reactive hyperemic index (RHI) of
      the IPAH patients was 1.54 (+/-0.69), and of the controls was 1.67 (+/-0.66) [p =
      0.64]. The mean baseline flow velocity in the segmental pulmonary artery of all
      patients was 18.5 (+/-5.5) cm/s, increasing to 27.4 (+/-12.3) cm/s (p = 0.003)
      during acetylcholine infusion. The calculated mean PFR was 1.48 (+/-0.4). There
      was no significant correlation between the PFR and RHI (r = 0.19; p = 0.54).
      According to our results, systemic arterial endothelial function assessed by
      peripheral arterial finger tonometry was not significantly impaired in children
      and young adults with IPAH compared with age-/gender-matched controls. There was
      no correlation between systemic arterial and pulmonary arterial endothelial
      function, suggesting that different mechanisms may contribute to their
      pathogenesis and progression.

PMID- 24442265
TI  - Can soluble adhesion molecules accurately predict carditis in acute rheumatic
      fever?

PMID- 24442267
TI  - Partitioning of variance and estimation of genetic parameters for various bristle
      number characters ofDrosophila melanogaster.
AB  - Phenotypic variance for each of several bristle number characters (abdominal,
      sternopleural, second and third coxal) was partitioned using both hierarchal and
      dialled designs. Heritabilities and genetic correlations were estimated from
      parent-offspring regressions and correlations and half-sib correlations.A high
      proportion of the genetic variance for abdominal bristle number was due to
      epistatic and sex-linked gene action, but most of the genetic variance for the
      other characters was additive autosomal.The genetic correlations among
      sternopleural, and second and third coxal bristle numbers were all high, but that
      between abdominals and sternopleurals was low, while those between abdominals and
      either second or third coxals were virtually zero. An appreciable proportion of
      the covariance between abdominal and sternopleural bristle numbers was non
      additive genetic.The diallel method gave more reliable estimates of genetic
      parameters when non-additive or sex-linked genetic variation was present. 

PMID- 24442268
TI  - [Further investigations on the resistance ofMedicago species toPseudopeziza
      medicaginis (Lib.) Sacc].
AB  - Experimental infections of 44 species and varieties ofMedicago with the f.
      sp.medicaginis sativae andmedicaginis lupulinae fromPseudopeziza medicaginis and
      withP. meliloti have broadened the knowledge on resistance behavior of the
      genusMedicago and confirmed earlier results. 

PMID- 24442266
TI  - Anti-inflammatory effects of carbon monoxide-releasing molecule on
      trinitrobenzene sulfonic acid-induced colitis in mice.
AB  - BACKGROUND AND AIM: Recent findings indicate that carbon monoxide (CO) in non
      toxic doses exerts a beneficial anti-inflammatory action in various experimental
      models. However, the precise anti-inflammatory mechanism of CO in the intestine
      remains unclear. Here, we assessed the effects of a novel water-soluble CO
      releasing molecule, CORM-3, on trinitrobenzene sulfonic acid (TNBS)-induced
      colitis in mice. METHODS: To induce colitis, C57BL/6 male mice received an enema
      of TNBS. CORM-3 or its inactive compound, iCORM-3, were administered
      intraperitoneally, once immediately before, and twice daily after receiving an
      enema of TNBS. Three days after TNBS administration, the distal colon was
      removed, assessed for colonic damage and histological scores, polymorphonuclear
      leukocyte recruitment (tissue-associated myeloperoxidase, MPO activity), and TNF
      alpha, IFN-gamma and IL-17A expression (mRNA and protein levels in the colon
      mucosa). CD4(+) T cells isolated from murine spleens were stimulated with anti
      CD3/CD28, in the presence or absence of CORM-3/iCORM-3. The cell supernatants
      were assessed for TNF-alpha and IFN-gamma expression, 24 h following stimulation.
      RESULTS: Colonic damage and histological scores were significantly increased in
      TNBS-induced mice compared to sham-operated mice. Tissue-associated MPO activity
      and expression of TNF-alpha, IFN-gamma, and IL-17A in the colonic mucosa were
      higher in TNBS-induced colitis mice. The above changes were attenuated in CORM-3
      treated mice. Further, CORM-3 was effective in reducing TNF-alpha and IFN-gamma
      production in anti-CD3/CD28-stimulated CD4(+) T cells. CONCLUSIONS: These
      findings indicate that CO released from CORM-3 ameliorates inflammatory responses
      in the colon of TNBS-challenged mice at least in part through a mechanism that
      involves the suppression of inflammatory cell recruitment/activation.

PMID- 24442269
TI  - [Free amino acids in endosperm ofRaphanus sativus L. after 4x*4x and 4x.2x
      crosses].
AB  - The amino acid pool in the endosperm of ovules ofRaphanus sativus var.sativus
      from 4x . 4x and 4x . 2x crosses was studied. There are striking differences
      between the two types of endosperm. In a normally functioning 6x endosperm (4x .
      4x) the amino acid concentrations decrease sharply, though temporarily,
      especially between the 12th and 15th day after pollination. In 5x endosperm (4x .
      2x) the amino acid concentrations are high and remain relatively unchanged. We
      assume this to be a metabolic anomaly and a possible cause for the degeneration
      of the embryo. 

PMID- 24442270
TI  - Preliminary testing of eastern cottonwood clones.
AB  - Broad-sense heritabilities were 0.44 to 0.47 for height, 0.24 to 0.28 for
      diameter, 0.26 to 0.29 for volume, 0.69 to 0.70 for specific gravity, 0.36 for
      fiber length, and 0.83 to 0.89 for resistance toMelampsora rust in a breeding
      population of 100 eastern cottonwood clones from central Mississippi grown for 1
      year on Commerce loam and Sharkey clay in 10*10 triple lattice designs.The effect
      of site was statistically significant for growth andMelampsora rust, but not for
      wood properties. On the heterogeneous Commerce loam site, the lattice design was
      more efficient than randomized blocks for evaluating growth but not other
      characters. Both genetic and phenotypic correlations between characters were low
      and, with the exception of height x diameter (r p =0.52 to 0.65), of no practical
      significance in selection. Major variation in form was observed. Large-diameter
      cuttings elongated significantly faster than small ones through August, after
      which the effect of cutting diameter was not statistically significant. 

PMID- 24442272
TI  - [Studies on the yield and quality of alfalfa varieties].
AB  - The correlations found between yield and content of several varieties of alfalfa
      show that selection for green matter only does not result in the deterioration of
      fodder quality. Green matter variability has more influence on the yield of dry
      matter, crude protein, and phosphoric acid than does the corresponding content;
      only the yield of carotene depends less on the green matter yield than on the
      carotene content.Variability in content decreases from carotene to phosphoric
      acid to crude protein, which makes the increase of carotene content easiest, that
      of crude protein hardest to achieve. 

PMID- 24442271
TI  - [The problem of egg and sperm preservation and its significance in fish
      breeding].
AB  - There would be new opportunities in the field of fish breeding, if it were
      possible to preserve the eggs and sperm.This problem of preservation, and later
      artificial fertilization under laboratory conditions, is dealt with in the text.
      The practical results of such a procedure are pointed out. 

PMID- 24442273
TI  - [The influence of gibberellic acid on the flower and cone development in hop
      (Humulus lupulus L.)].
AB  - The treatment of the three hop-varieties 'Saazer', 'Huller Anfang' and
      'Hallertauer' with gibberellic acid caused a decrease of the 1000-cone weight,
      but an increase in cones of each plant.With 'Huller Anfang' and 'Hallertauer'
      there was a decrease in alpha-acid content, in the 'Saazer' variety it remained
      equal, only when it was treated by the dosage 10 ppm, times two, an icrease in
      alpha-acid content resulted.The organoleptic valuation of the cones showed a
      decrease in quality especially in respect to cone size, Jupulin content and
      delicacy of aroma. In the 'Huller Anfang' variety a high percentage of cock hops
      resulted also.Under the influence of gibberellic acid the development of the hop
      plant is prolonged, so that the ripening of cones is retarded. Early and middle
      early varieties thus become middle-early and late varieties.The female flower is
      somewhat retarded in development; in the extreme case this leeds to complete
      suppression of all flower parts and a tendency to reduce the female inflorescence
      to the original leaf shoot. Moreover, the hybrid variety 'Huller Anfang' formed
      monoecious plants. The origin of monoecious plants is discussed.The different
      reactions to treatment with gibberellic acid of the several varieties are caused
      by the differing stages of plant development at the time of treatment. 

PMID- 24442274
TI  - Measurement of supramolecular effective molarities for intramolecular H-bonds in
      zinc porphyrin-imidazole complexes.
AB  - The association constants for formation of 1 : 1 complexes between five different
      imidazole ligands and eight different porphyrins have been measured by UV/vis
      titration experiments in two different solvents, toluene and 1,1,2,2
      tetrachloroethane (TCE). Ligands equipped with H-bond acceptors (ester or amide)
      and porphyrins equipped with H-bond donors (phenol) can make H-bonds in addition
      to the zinc-nitrogen coordination interaction. The free energy contributions of
      these H-bonds to the overall stabilities of the complexes were determined using
      chemical double mutant cycles. Amide-phenol H-bonds contribute up to 5 kJ mol(-1)
      to the free energy change on complexation, and ester-phenol H-bonds contribute up
      to 3 kJ mol(-1). Porphyrin-ligand combinations with poor geometric
      complementarity do not make detectable H-bonding interactions. Effective
      molarities (EM) for the formation of H-bonds in the complexes were estimated by
      comparing the equilibrium constants for formation of the intramolecular
      interaction with the corresponding intermolecular interaction: the values are
      between 3 mM and 200 mM, which is comparable to previous results obtained for
      porphyrin-pyridine complexes. The values of EM measured for flexible and rigid
      ligand systems are comparable. This suggests that there is a trade off between
      restriction of conformational mobility in the flexible ligands and geometric
      strain in the rigid ligands, which results in similar binding affinities. 

PMID- 24442275
TI  - Transoral anterior revision surgeries for basilar invagination with irreducible
      atlantoaxial dislocation after posterior decompression: a retrospective study of
      30 cases.
AB  - PURPOSE: To report the surgical techniques and clinical results of one-stage
      transoral anterior revision surgeries for basilar invagination (BI) with
      atlantoaxial dislocation (AAD) after posterior decompression. METHODS: From
      September 2008 to June 2012, 30 patients (16 men and 14 women) who had BI with
      irreducible atlantoaxial dislocation (IAAD) after posterior decompression
      underwent anterior revision surgeries in our department. Dynamic cervical
      radiographs, computed tomographic scans and magnetic resonance imaging were
      obtained pre- and postoperatively to assess the degree of AAD and ventral
      compression on the cervical cord. The JOA scoring system was used to evaluate the
      neurological status. The revision surgeries were conducted by anterior approach,
      using the transoral atlantoaxial reduction plate (TARP) system. RESULTS: The
      revision surgeries were successfully performed in all of the cases. The average
      follow-up duration was 16 months (range 6-39 months). For all of the cases,
      complete or more than 50 % reduction and decompression of C1-C2 were achieved.
      The cervicomedullary angle was improved by an average of 32.9 degrees . Bone
      fusion was achieved within 3-6 months in all of the cases. Clinical symptoms were
      alleviated in 29 patients (96.7 %) and stabilised in 1 patient (3.3 %). No
      patients have developed recurrent or progressive atlantoaxial instability so far.
      CONCLUSION: Anterior revision surgeries using the TARP system achieved reduction,
      decompression and fixation of C1-C2 in one stage for BI with IAAD. This technique
      offers an effective, simple and safe method for the revision of such cases after
      posterior decompression.

PMID- 24442276
TI  - Protamine sulfate-calcium carbonate-plasmid DNA ternary nanoparticles for
      efficient gene delivery.
AB  - Ternary nanoparticles, protamine sulfate-calcium carbonate-plasmid DNA (PS-CaCO3
      DNA), were prepared for efficient gene delivery. By adding the cationic
      polypeptide PS in the co-precipitation system of calcium carbonate and DNA, PS
      CaCO3-DNA nanoparticles could be formed by self-assembly facilely. The effect of
      PS on the properties of the ternary nanoparticles was studied by varying the PS
      amount in the nanoparticles. The size and zeta-potential measurements indicated
      that the ternary nanoparticles with an appropriate PS amount exhibited a
      decreased size and an increased zeta-potential. The in vitro gene transfections
      mediated by different nanoparticles in 293T cells and HeLa cells were carried out
      in the presence of 10% fetal bovine serum, using pGL3-Luc and pEGFP-C1 as
      reporter plasmids. As compared with both PS-DNA nanoparticles and CaCO3-DNA
      nanoparticles, PS-CaCO3-DNA nanoparticles exhibited significantly enhanced gene
      delivery efficiency, which was higher than that of Lipofectamine 2000-DNA.
      Confocal microscopy observation showed that PS-CaCO3-DNA nanoparticles could
      efficiently deliver DNA to cell nuclei. These results indicated that the ternary
      PS-CaCO3-DNA nanoparticles prepared in this study have promising applications in
      gene delivery. 

PMID- 24442278
TI  - Imaging performance of LabPET APD-based digital PET scanners for pre-clinical
      research.
AB  - The LabPET is an avalanche photodiode (APD) based digital PET scanner with quasi
      individual detector read-out and highly parallel electronic architecture for high
      performance in vivo molecular imaging of small animals. The scanner is based on
      LYSO and LGSO scintillation crystals (2*2*12/14 mm3), assembled side-by-side in
      phoswich pairs read out by an APD. High spatial resolution is achieved through
      the individual and independent read-out of an individual APD detector for
      recording impinging annihilation photons. The LabPET exists in three versions,
      LabPET4 (3.75 cm axial length), LabPET8 (7.5 cm axial length) and LabPET12 (11.4
      cm axial length). This paper focuses on the systematic characterization of the
      three LabPET versions using two different energy window settings to implement a
      high-efficiency mode (250-650 keV) and a high-resolution mode (350-650 keV) in
      the most suitable operating conditions. Prior to measurements, a global timing
      alignment of the scanners and optimization of the APD operating bias have been
      carried out. Characteristics such as spatial resolution, absolute sensitivity,
      count rate performance and image quality have been thoroughly investigated
      following the NEMA NU 4-2008 protocol. Phantom and small animal images were
      acquired to assess the scanners' suitability for the most demanding imaging tasks
      in preclinical biomedical research. The three systems achieve the same radial FBP
      spatial resolution at 5 mm from the field-of-view center: 1.65/3.40 mm
      (FWHM/FWTM) for an energy threshold of 250 keV and 1.51/2.97 mm for an energy
      threshold of 350 keV. The absolute sensitivity for an energy window of 250-650
      keV is 1.4%/2.6%/4.3% for LabPET4/8/12, respectively. The best count rate
      performance peaking at 362 kcps is achieved by the LabPET12 with an energy window
      of 250-650 keV and a mouse phantom (2.5 cm diameter) at an activity of 2.4 MBq ml
      1. With the same phantom, the scatter fraction for all scanners is about 17% for
      an energy threshold of 250 keV and 10% for an energy threshold of 350 keV. The
      results obtained with two energy window settings confirm the relevance of high
      efficiency and high-resolution operating modes to take full advantage of the
      imaging capabilities of the LabPET scanners for molecular imaging applications.

PMID- 24442279
TI  - Molecular arrangement of pigment-protein complex of photosystem 1.
AB  - The circular dichroism (CD) method was applied to study the molecular
      organization of P700, antenna chlorophyll and protein of photosystem 1 complexes
      (CP1), isolated from chloroplasts under mild treatment with Triton X-100.
      Analysis of CD spectra and protein: chlorophyll: P700 ratios for CP1 complexes
      that were different in their chlorophyll content indicate that CP1 preparations
      can be considered as a mixture of CP1-RC, containing P700 (10-20%), and CP1-LH
      without P700 (80-90%). Both types of complexes contain approximately 25
      chlorophyll molecules, and the destruction of their spatial organization with
      detergents represents a cooperative transition. The rate of chlorophyll
      destruction in CP1-LH is much higher than that in CP1-RC. In both complexes a 65
      kDa polypeptide predominates, whose secondary structure (typical for alpha/beta
      proteins) is stable to Triton X-100 and does not depends on the chlorophyll
      content. Chlorophyll seems to be grouped in clusters (5-7 molecules) in the
      hydrophobic cores of 2-3 parallel alpha/beta domains of the 65 kDa protein. Only
      one of the clusters in CP1-RC includes P700; on P700 photooxidation the change of
      its interaction with the nearest pigment environment results in a complicated
      shape of the light-induced CD spectra. 

PMID- 24442277
TI  - DRM1 and DRM2 expression regulation: potential role of splice variants in
      response to stress and environmental factors in Arabidopsis.
AB  - The DRM1/ARP gene family is increasingly exhibiting associations with stress
      conditions at the transcript level. Traditionally correlated with dormancy,
      increases in transcript levels in response to various treatments have also been
      reported in various species. As alternative transcript splicing is common in
      stress conditions, the splice variants of AtDRM1 and AtDRM2 were assessed further
      in this study. A previously undescribed splice variant of AtDRM1 (AtDRM1.6) is
      introduced in this work. In silico analyses of predicted protein sequence of all
      splice variants showed that all variants retain the predicted intrinsically
      disordered nature. Transcriptional studies of AtDRM1 and AtDRM2 in response to a
      wide range of abiotic, physical and hormonal treatments showed that AtDRM1.6 is
      differentially regulated at the transcriptional level compared with other splice
      variants. Promoter analyses demonstrated AtDRM1 light regulation via the upstream
      promoter sequence. 

PMID- 24442280
TI  - Optical effects of sodium dodecyl sulfate treatment of the isolated light
      harvesting complex of higher plants.
AB  - The light-harvesting complex (LHC) of higher plants isolated using Triton X-100
      has been studied during its transformation into a monomeric form known as CPII.
      The change was accomplished by gradually increasing the concentration of the
      detergent, sodium dodecyl sulfate (SDS). Changes in the red spectral region of
      the absorption, circular dichroism (CD), and linear dichroism spectra occurring
      during this treatment have been observed at room temperature. According to a
      current hypothesis the main features of the visible region absorption and CD
      spectra of CPII can be explained reasonably successfully in terms of an exciton
      coupling among its chlorophyll (Chl) b molecules. We suggest that the spectral
      differences between the isolated LHC and the CPII may be understood basically in
      terms of an exciton coupling between the Chl b core of a given CPII unit and at
      least one of the Chla's of either the same or the adjacent CPII. We propose that
      this Chl a-Chl b coupling existing in LHC disappears upon segregation into CPII,
      probably as a result of a detergent-related overall rotation of the strongly
      coupled Chl b core which changes the relative orientations of the two types of
      pigments and thus the nature of their coupling. 

PMID- 24442281
TI  - Interactions of the bacteriochlorophylls in antenna bacteriochlorophyll-protein
      complexes of photosynthetic bacteria.
AB  - Several models have been proposed for the arrangements of the
      bacteriochlorophylls in the antenna complexes of purple photosynthetic bacteria,
      but none of the models has accounted fully for the spectroscopic properties of
      the bacteriochlorophyll-protein complexes. We suggest a model involving strong
      exciton interactions within a bacteriochlorophyll dimer, and weaker interactions
      of each dimer with other, relatively distant dimers. The model is shown to
      account for the spectroscopic properties of the complexes, and to be consistent
      with other available information. 

PMID- 24442282
TI  - Pigment organization and energy transfer in the green photosynthetic bacterium
      Chloroflexus aurantiacus : II. The chlorosome.
AB  - The transfer of excitation energy and the pigment arrangement in isolated
      chlorosomes of the thermophilic green bacterium Chloroflexus aurantiacus were
      studied by means of absorption, fluorescence and linear dichroism spectroscopy,
      both at room temperature and at 4 K. The low temperature absorption spectrum
      shows bands of the main antenna pigments BChl c and carotenoid, in addition to
      which bands of BChl a are present at 798 and 613 nm. Fluorescence measurements
      showed that excitation energy from BChl c and carotenoid is transferred to BChl
      a, which presumably functions as an intermediate in energy transfer from the
      chlorosome to the cytoplasmic membrane. Measurements of fluorescence polarization
      and the use of two different orientation techniques for linear dichroism
      experiments enabled us to determine the orientation of several transition dipole
      moments with respect to each other and to the three principal axes of the
      chlorosome. The Qy transition of BChl a is oriented almost perfectly
      perpendicular to the long axis of the chlorosome. The Qy transition of BChl c and
      the gamma-carotene transition dipole are almost parallel to each other. They make
      an angle of about 40 degrees  with the long axis and of about 70 degrees  with
      the short axis of the chlorosome; the angle between these transitions and the
      BChl a Qy transition is close to the magic angle (55 degrees ). 

PMID- 24442283
TI  - Photosystem I photochemistry: A new kinetic phase at low temperature.
AB  - A new phase of charge recombination between the oxidized primary electron donor
      of photosystem I (P700(+)) and a reduced acceptor has been detected by flash
      absorption spectroscopy in PS I particles at low temperature. It occurs under
      highly reducing conditions (the secondary electron acceptors FA and FB and one or
      possibly two 'more primary' acceptors being prereduced) with a t1/2 of about 20
      MUs between 10 and 80 K. 

PMID- 24442284
TI  - Thermodynamics of the charge recombination in photosystem II.
AB  - The temperature dependence of the electric field-induced chlorophyll luminescence
      in photosystem II was studied in Tris-washed, osmotically swollen spinach
      chloroplasts (blebs). The system II reaction centers were brought in the state
      Z(+)P(+)-QA (-)QB (-) by preillumination and the charge recombination to the
      state Z(+)PQAQB (-) was measured at various temperatures and electrical field
      strengths. It was found that the activation enthalpy of this back reaction was
      0.16 eV in the absence of an electrical field and diminished with increasing
      field strength. It is argued that this energy is the enthalpy difference between
      the states IQA (-) and I(-)QA and accounts for about half of the free energy
      difference between these states. The redox state of QB does not influence this
      free energy difference within 150 MUs after the photoreduction of QA. The
      consequences for the interpretation of thermodynamic properties of QA are
      discussed. 

PMID- 24442285
TI  - Stoichiometric determination of pheophytin in photosystem II of oxygenic
      photosynthesis.
AB  - Pheophytin and chlorophyll extracted from oxygen-evolving photosystem II
      particles, chloroplast thylakoids and cyanobacterial cells were separated by
      column chromatography with DEAE-Toyopearl, and quantitatively determined by
      spectrophotometry. The molecular ratio of chlorophyll a+b to pheophytin a was
      about 100 in spinach photosystem II particles and about 140 in spinach
      thylakoids. Using flash spectrophotometry of P680 and measurement of flash
      induced oxygen yield, the molecular ratio of the chlorophyll to the photochemical
      reaction center II was determined to be about 200 in the photosystem II
      particles. These findings suggest that the stoichiometry in photosystem II
      particles is one reaction center II and two pheophytin a molecules per about 200
      chlorophyll molecules. The same stoichiometry for pheophytin to the reaction
      center II was obtained in the cyanobacteria, Anacystis nidulans and Synechocystis
      PCC 6714. A quantitative determination of pheophytin a and the electron donor
      P700 in stroma thylakoids from pokeweed suggests that photosystem I does not
      contain pheophytin. 

PMID- 24442286
TI  - Total recovery of O2 evolution and nanosecond reduction kinetics of chlorophyll-a
      II (+) (P-680 (+)) after inhibition of water cleavage with acetate.
AB  - Oxygen evolution and reduction kinetics of the photooxidized Chl-aII (+) have
      been measured in oxygen-evolving complexes from the thermophilic cyanobacterium
      Synechococcus sp. 1. Incubation of PS II particles with acetate resulted in an
      inhibition of oxygen evolution and a retardation of the Chl-aII (+)=reduction
      kinetics from the nanosecond range to the microsecond range, indicating a
      modification of the donor side of photosystem II (PS II). 2. After the first two
      flashes given to a dark-adapted, acetate treated sample, Chl-aII (+) was re
      reduced with a half-life time of 160 MUs by a component of the donor side of PS
      II. Under repetitive excitation Chl-aII (+) was re-reduced in 500 MUs by electron
      back reaction from the primary acceptor QA (-) (X-320(-)). Obviously, in the
      presence of acetate only two electrons are available from the donor side. 3. Both
      oxygen evolution and nanosecond reduction kinetics of Chl-aII (+) were restored
      to the control level when acetate was removed. 4. The results indicate a tight
      coupling between O2 evolution and nanosecond reduction kinetics of Chl-aII (+).
      5. The reversible inhibition is probably due to a replacement of Cl(-) by acetate
      within the water splitting enzyme. 6. Due to its strongly retarded kinetics, the
      reversibly modified system may facilitate investigations of the mechanism of the
      donor side. 

PMID- 24442287
TI  - Mechanism of photoinhibition: photochemical reaction center inactivation in
      system II of chloroplasts.
AB  - Photoinhibition of photosynthesis is manifested at the level of the leaf as a
      loss of CO2 fixation and at the level of the chloroplast thylakoid membrane as a
      loss of photosystem II electron-transport capacity. At the photosystem II level,
      photoinhibition is manifested by a lowered chlorophyll a variable fluorescence
      yield, by a lowered amplitude of the light-induced absorbance change at 320 nm
      (DeltaA320) and 540-minus-550 nm (DeltaA540-550), attributed to inhibition of the
      photoreduction of the primary plastoquinone QA molecule. A correlation of the
      kinetics of variable fluorescence yield loss with the inhibition of QA
      photoreduction suggested that photoinhibited reaction centers are incapable of
      generating a stable charge separation but are highly efficient in the trapping
      and non-photochemical dissipation of absorbed light. The direct effect of
      photoinhibition on primary photochemical parameters of photosystem II suggested a
      permanent reaction center modification the nature of which remains to be
      determined. 

PMID- 24442288
TI  - Triplet-minus-singlet absorbance difference spectra of reaction centers of
      Rhodopseudomonas sphaeroides R-26 in the temperature range 24-290 K measured by
      Magneto-Optical Difference Spectroscopy (MODS).
AB  - The recently developed technique of Magneto-Optical Difference Spectroscopy
      (MODS) [10] has been applied to reaction centers (RC) of the photosynthetic
      bacterium Rhodopseudomonas sphaeroides R-26. Absorbance changes induced by a
      magnetic field are measured as a function of wavelength yielding the triplet
      minus-singlet (T-S) absorbance difference spectrum. (T-S) spectra thus obtained
      have been measured from 24-290 K. Going from low to high temperature the (T-S)
      spectra show the following features: (a) A rapid decrease of positive absorption
      bands at 809 and 819 nm. (b) A slow appearance of a band shift at 798 nm. (c) A
      shift of the peak wavelength of the Qy absorbance band of the primary donor P-860
      from 992 to 861 nm, and of its Qx band from 603 to 600 nm. The spectra at 24, 66,
      116, and 290 K have been analyzed by Gaussian deconvolution. The 800 nm region of
      the spectrum at 24 K can be decomposed in a combination of two band shifts and an
      appearing band. The temperature dependence of the spectra in this region is well
      explained by spectral broadening of the two shifting bands combined with a
      decrease in intensity of the appearing band when the temperature increases.The
      two shifting bands in the 800 nm region are identified as the two bands at 803
      and 813 nm which together make up the 800 nm band in the absorption spectrum and
      are assigned to the two accessory RC bacteriochlorophylls (BChls). The band shift
      of the 813 nm pigment is appreciably larger than that of the 803 nm pigment. The
      appearing band at 808 nm is attributed to monomeric absorption of (3)P-860, the
      triplet state being localized on one BChl.We find no evidence for admixture of a
      charge transfer (CT) state of (3)P-860 with one of the accessory BChls at higher
      temperature. 

PMID- 24442289
TI  - Manganese-histidine cluster as the functional center of the water oxidation
      complex in photosynthesis.
AB  - The recent model of Kambara and Govindjee for water oxidation [Kambara T. and
      Govindjee (1985) Proc. Natl. Acad. Sci. U.S.A., 82:6119-6123] has been extended
      in this paper by examining all the data in order to identify the most likely
      candidate for the 'redox-active ligand' (RAL), suggested to operate between the
      water oxidizing complex (WOC) and Z, the electron donor to the reaction center
      P680. We have concluded that a very suitable candidate for RAL is the imidazole
      moiety of a histidine residue. The electrochemical data available on imidazole
      derivatives play heavily in this identification of RAL. Thus, we suggest that
      histidine might play the role of an electron mediator between the WOC and Z. A
      model of S-states in terms of their plausible chemical identity is presented
      here. 

PMID- 24442290
TI  - Mechanism of proton-pumping in the cytochrome b/f complex.
AB  - Several models have been proposed to interpret the mechanism of proton-pumping
      associated with the electron transfer reactions in the cytochrome b/f complex.
      Energetics considerations suggest that the proton pump is coupled to the
      oxidation of cytochrome b by plastoquinone. Experiments performed in living cells
      under anaerobic conditions suggest that proton-pumping can occur through two
      independent mechanisms. When the two b cytochromes are reduced prior to a flash
      illumination i.e. after a long dark anaerobic incubation (>10 minutes), proton
      pumping is very likely associated with the reduction of a semiquinone by cyt b
      which occurs at a site close to the inner face of the membrane. The electrogenic
      phase is associated with the tranfer of protons via a transmembrane channel. This
      process is not inhibited by 2-n-nonyl-4-hydroxyquinoline N-oxide (NQNO). Under
      repetitive-flash or under aerobic conditions, proton-pumping occurs according to
      a modified Q-cycle mechanism, which is inhibited by NQNO. 

PMID- 24442291
TI  - ESR spectroscopy demonstrates that cytochrome b559 remains low potential in Ca
      (2+)-reactivated, salt-washed PSII particles.
AB  - Cytochrome b559 in various Photosystem II preparations was studled by using low
      temperature ESR spectroscopy. This technique was used because it is able to
      distinguish high from low potential forms of the cytochrome owing to the g-value
      differences between these species. Moreover, by using low temperature irradiation
      to oxidize cyt b559 we have avoided the use of redox mediators. Previous work
      (Ghanotakis DF., Topper J.N. and Yocum, C.F. (1984) Biochim. Biophys. Acta 767,
      524-531) demonstrated that reduction and extraction of manganese of the oxygen
      evolving complex, which might be expected to alter the redox properties of cyt
      b559, occurs when certain PSII preparations are exposed to reductants. The ESR
      data presented here show that a mixture of high potential and lower potential cyt
      b559 species is observed in the oxygen evolving Photosystem II complex. Treatment
      of PSII membranes with 0.8 M Tris converts the high potential form(s) to those of
      lower potential. Exposure of the membranes to 2M NaCl shifts a significant amount
      of high potential cyt b559 to lower potential form(s); addition of CaCl2
      reconstituted oxygen evolution activity but did not restore cyt b559 to its high
      potential form(s). 

PMID- 24442292
TI  - Photosynthetic and respiratory electron transport in a cyanobacterium.
AB  - In the cyanobacterium Agmenellum quadruplicatum steady-state redox conditions
      were monitored in vivo for cytochrome (delta+c553) and P700 versus intensities of
      an actinic light 1 or light 2 (mainly absorbed by photosystems, and 2,
      respectively). Parallel measurements of O2 evolution were used to calibrate
      intensities for rates of electron transfer. Results show that the quality of
      actinic light (as light 1 or light 2) depends on intensity as well as wavelength.
      The contribution of electron flow from respiration is confirmed by observations
      of relative rate of photoreaction 1 estimated from Ip (intensity * fraction of
      P700 reduced). With 3,- (3,4-dichlorophenyl-1, 1-dimethylurea) (DCMU) the rate of
      photoreaction 1 depends upon, and is sensitive to small changes in, the rate of
      dark respiration. Very slow transient dark reductions of Cyt (f+c553) and P700
      following any low intensity actinic light 1 are attributed to respiratory
      electron flow. Cyclic electron flow around photoreaction 1 cannot be large
      compared to dark respiration and cannot vary significantly with light intensity. 

PMID- 24442293
TI  - Anoxygenic photosynthetic hydrogen production and electron transport in the
      cyanobacterium oscillatoria limnetica.
AB  - The induction of anoxygenic photosynthesis in the cyanobacterium Oscillatoria
      limnetica by sulfide was shown to involve the synthesis of a "sulfide oxidizing
      factor"; this factor, partly adsorbed on the thylakoid membrane, can be recovered
      in the soluble phase and is active also on membranes from oxygenically grown
      cells. The factor is required for sulfide dependent light-induced hydrogen
      evolution. It accelerates electron transport from sulfide to the electron donor
      of photosystem I, P700, in membranes from cells in which anoxygenic
      photosynthesis is induced. The plastiquinone analogue DBMIB does not inhibit
      electron transport to P700 but accelerates it. The analogue might promote cyclic
      electron transport involving P700, thus preventing electrons to reach
      hydrogenase. 

PMID- 24442294
TI  - Oxidation of cytochrome c 2 by photosynthetic reaction centers of Rhodospirillum
      rubrum and Rhodopseudomonas sphaeroides in vivo. Effect of viscosity on the rate
      of reaction.
AB  - In Rhodospirillum rubrum and Rhodopseudomonas sphaeroides it is shown that the
      oxidation of cytochrome c 2 involves a diffusion limited process. From analysis
      of the results it follows that the electron transfer probability must be very
      low. This is corroborated by in vitro studies using the isolated components. 

PMID- 24442295
TI  - Photooxidation of mitochondrial cytochrome c by isolated bacterial reaction
      centers: Evidence for tight-binding and diffusional pathways.
AB  - The binding of horse heart mitochondrial cytochrome c to isolated reaction
      centers from Rhodopseudomonas sphaeroides is described. The kinetics of
      photooxidation of cytochrome c following a short actinic flash is compared to the
      expected binding state of the cytochrome at various concentrations and at
      different ionic strengths. At low ionic strength a very tight binding site
      (KD?10(-8) M) is apparent which is nonfunctional with respect to electron
      donation to the bound reaction center. This tightly bound cytochrome can react
      with another reaction center in a diffusion limited, second order process. A
      weaker binding site (KD?0.3 . 10(-6) M) is also boserved which is associated with
      rapid, first order electron transfer from cytochrome to reaction center. Both
      binding processes are weakened in the presence of salt and there is no detectable
      binding in 100 mM NaCl. Under such conditions cytochrome oxidation is entirely a
      diffusional, second order process. However, analysis of the flash intensity
      dependence of the extent of cytochrome oxidation, by the method of van Grondelle
      (van Grondelle, R. (1978) Ph.D. Thesis, State University, Leiden) indicated that
      the cytochrome was not freely mobile even in 100 mM NaCl, at least in the sense
      that reduced cytochrome only slowly dissociates from unactivated reaction
      centers. An overall kinetic/equilibrium scheme for cytochrome c binding and
      photooxidation by reaction centers is presented. This is very similar to that
      described earlier for cytochrome c2 (Overfield, R.E., Wraight, C.A. and DeVault,
      D. (1979) FEBS Lett. 105, 137-142), but the tight binding site and associated
      diffusion controlled oxidation is unique to cytochrome c. 

PMID- 24442296
TI  - Isolation of cytochrome bc 1 complexes from the photosynthetic bacteria
      Rhodopseudomonas viridis and Rhodospirillum rubrum.
AB  - Cytochrome bc 1 complexes have been isolated from wild type Rhodopseudomonas
      viridis and Rhodospirillum rubrum and purified by affinity chromatography on
      cytochrome c-Sepharose 4B. Both complexes are largely free of bacteriochlorophyll
      and carotenoids and contain cytochromes b and c 1 in a 2:1 molar ratio. For the
      Rps. viridis complex, evidence has been obtained for two spectrally distinct b
      cytochromes. The R. rubrum complex contains a Rieske iron-sulfur protein (present
      in approximately 1:1 molar ratio to cytochrome c 1) and catalyzes an antimycin A-
      and myxothiazol-sensitive electron transfer from duroquinol to equine cytochrome
      c or R. rubrum cytochrome c 2. Although an attempt to prepare a cytochrome bc 1
      complex from the gliding green bacterium Chloroflexus aurantiacus was not
      successful, membranes isolated from phototrophically grown Cfl. aurantiacus were
      shown to contain a Rieske iron-sulfur protein and protoheme (the prosthetic group
      of b-type cytochromes). 

PMID- 24442297
TI  - On the action of hydroxylamine, hydrazine and their derivatives on the water
      oxidizing complex.
AB  - Photosynthetic water oxidation proceeds by a four-step sequence of one-electron
      oxidations which is formally described by the transitions S0 -> S1, S1 -> S2, S2 
      > S3, S3 -> (S4) -> S0. State S1 is most stable in the dark. Oxygen is released
      during S3 -> (S4) -> S0. Hydroxylamine and hydrazine interact with S1. They cause
      a two-digit shift in the oxidation sequence as observed from the dark
      equilibrium, i.e. from S1 -> S2 : S2 -> S3 : S3 -> (S4) -> S0 : S0 -> S1 :... in
      the absence of the agents, to S1 (*) -> S0 : S0 -> S1 : S1 -> S2 : S2 -> S3 :...
      in the presence of hydroxylamine or hydrazine.We measured the concentration
      dependence of this two-digit shift via the pattern of proton release which is
      associated with water oxidation. At saturating concentrations hydroxylamine and
      hydrazine shift the proton-release pattern from OH(+)(S1 -> S2) : 1H(+)(S2 -> S3)
      : 2H(S3 -> S0) : 1H(+)(S0 -> S1) :... to 2H(+)(S1 (*) -> S0) : 1H(+)(S0 -> S1) :
      OH(+)(S1 -> S2) : 1H(+)(S2 -> S3) : 2H(+)(S3 -> S0) :... The 2H(+) were released
      upon the first excitation with a half-rise time of 3.1 ms, both with
      hydroxylamine and withydrazine. The concentration dependence of the shift was
      rather steep with an apparent Hill coefficient at half saturation of 2.43 with
      hydroxylamien (Forster and Junge (1985) FEBS Lett. 186, 53-57) and 1.48 with
      hydrazine. The concentration dependence could be explained by cooperative binding
      of n>=3 molecules of hydroxylamine and of n>=2 molecules of hydrazine,
      respectively. Tentatively, we explain the interaction of hydroxylamine and
      hydrazine with the water-oxidizing complex (WOC) as follows: Two bridging
      ligands, possible Cl(-) or OH(-), which normally connect two Mn nuclei, can be
      substituted by either 4 molecules of hydroxylamine or 2 molecules of hydrazine
      when the WOC resides in state S1. 

PMID- 24442298
TI  - Photosynthetic free energy transduction related to the electric potential changes
      across the thylakoid membrane.
AB  - A model based on our present knowledge of photosynthetic energy transduction is
      presented. Calculated electric potential profiles are compared with
      microelectrode recordings of the thylakoid electric potential during and after
      actinic illumination periods of intermediate duration. The information content of
      the measured electric response is disclosed by a comparison of experimental
      results with calculations. The proton flux through the ATP synthase complex is
      seen to markedly influence the electric response. Also the imbalance in maximum
      turnover rate between the two photosystems, common to obligate shade plants like
      Peperomia metallica used in the microelectrode experiments, is clearly reflected
      in the electric potential profile. 

PMID- 24442299
TI  - Energization and ultrastructural pattern of thylakoids formed under periodic
      illumination followed by continuous light.
AB  - Bean leaves grown under periodic illumination (56 cycles of 2 min light and 98
      min darkness) were subsequently exposed to continuous illumination, and in
      connection with granum formation and accumulation of the light-harvesting pigment
      protein complex thermoluminescence and light-induced shrinkage of thylakoid
      membranes were studied. Juvenile chloroplasts with large double sheets of
      thylakoids obtained under periodic light exhibited low temperature spectra of
      polarized fluorescence yielding fluorescence polarization (FP) values < 1 at 695
      nm, characteristic for pheophytin emission. In the course of maturation under
      continuous light when normal grana appeared and the chlorophyll a/b light
      harvesting photosystem II complex was incorporated into the membrane, at 695 nm
      the relative intensity of fluorescence dropped and FP changed to a value of > 1,
      suggesting an overlap between the emission of pheophytin and that of the
      chlorophyll a/b light-harvesting photosystem II complex. Thermoluminescence glow
      curves recorded with juvenile thylakoids displayed a relatively high proportion
      of emission at low temperatures (around -10 degrees C) while with mature
      chloroplasts, more thermoluminescence originated from energetically deeper traps
      (discharged around 28 degrees C). This means that during thylakoid development
      the capacity of the membrane to stabilize the separated charges increases, which
      might be favourable for the ultimate conservation of energy. The more extensive
      energization of mature thylakoids was also indicated by a light-induced decrease
      in the thickness of the membranes upon illumination; a change which could not be
      detected in juvenile thylakoids. 

PMID- 24442300
TI  - What role does sulpholipid play within the thylakoid membrane?
AB  - Sulphoquinovosyldiacylglycerol is a negatively charged lipid which exists in the
      thylakoid membrane. It is proposed that a large proportion of this acidic lipid
      does not form a part of the bulk lipid matrix but is closely associated with
      protein complexes where it is tightly bound and participates in either optimising
      catalytic activities, or maintaining the complexes in a functional conformation.
      Experimental evidence for this proposal is emerging from studies with isolated
      photosystem 2, and coupling factor complexes. 

PMID- 24442301
TI  - Photosynthesis 3.5 thousand million years ago.
AB  - The recent discovery of stromatolites and microfossils in 3.5-Ga-old sedimentary
      rock formations is evidence for the existence of phototrophic prokaryotes at that
      time. Values of delta(13)C for sedimentary organic carbon strongly suggest
      autotrophic CO2 fixation, and the existence of large deposits of sedimentary
      sulfate is consistent with a photosynthesis dependent on reduced sulfur compounds
      for reducing power. The ancient photoautotrophs are though to have contained only
      one kind of reaction center with either chlorophyll a or bacteriochlorophyll a as
      primary electron donor and with one or more iron-sulfur centers as secondary
      electron acceptors. Light-harvesting pigments might have been chlorophyll a,
      bacteriochlorophyll a, or possibly bacteriochlorophyll c.A new proposal is made
      to explain how these organisms could have survived an intense UV flux at the
      earth's surface in the absence of an ozone layer. Photochemically produced ferric
      iron was abundant in sediments, and the UV-absorption of this ferric iron would
      have been sufficient to shield those organisms living below the watersediment
      interface. 

PMID- 24442302
TI  - Detection of rapid induction kinetics with a new type of high-frequency modulated
      chlorophyll fluorometer.
AB  - A newly developed modulation fluorometer is described which operates with 1 MUsec
      light pulses from a light-emitting diode (LED) at 100 KHz. Special amplification
      circuits assure a highly selective recording of pulse fluorescence signals
      against a vast background of non-modulated light. The system tolerates ratios of
      up to 1:10(7) between measuring light and actinic light. Thus it is possible to
      measure the "dark fluorescence yield" and record the kinetics of light-induced
      changes. A high time resolution allows the recording of the rapid relaxation
      kinetic following a saturating single turnover flash. Examples of system
      performance are given. It is shown that following a flash the reoxidation
      kinetics of photosystem II acceptors are slowed down not only by the inhibitor
      DCMU, but by a number of other treatments as well. From a light intensity
      dependency of the induction kinetics the existence of two saturated intermediate
      levels (I1 and I2) is apparent, which indicates the removal of three distinct
      types of fluorescence quenching in the overall fluorescence rise from F0 to Fmax.

PMID- 24442303
TI  - A Monte Carlo method for the simulation of kinetie models.
AB  - The purpose of this note is to illustrate the feasibility of simulating kinetic
      systems, such as commonly encountered in photosynthesis research, using the Monte
      Carlo (MC) method. In this approach, chemical events are considered at the
      molecular level where they occur randomly and the macroscopic kinetic evolution
      results from averaging a large number of such events. Their repeated simulation
      is easily accomplished using digital computing. It is shown that the MC approach
      is well suited to the capabilities and resources of modern microcomputers. A
      software package is briefly described and discussed, allowing a simple
      programming of any kinetic model system and its resolution. The execution is
      reasonably fast and accurate; it is not subject to such instabilities as found
      with the conventional analytical approach. 

PMID- 24442304
TI  - Introduction.

PMID- 24442305
TI  - Foreword.

PMID- 24442306
TI  - Simulation of genetic systems : XI. Normalizing selection.
AB  - The effects of intense normalizing selection have been studied, using computer
      simulation, for models of 3, 4, 5, 6, 8, 12 and 24 loci. The effectiveness of
      such selection in reducing heterozygosity decreases with increase of the number
      of loci to a limit that is only slightly greater than that consequent from random
      genetic dispersion, if the loci are freely recombining. Tight linkage markedly
      reduces the rate of loss of heterozygosity for small numbers of loci, but this
      effect of tight linkage decreases with increase of the number of loci. 

PMID- 24442307
TI  - Linkage disequilibrium in finite populations.
AB  - A theoretical investigation has been made of the influence of population size (N)
      and recombination fraction (c) on linkage disequilibrium (D) between a pair of
      loci. Two situations were studied: (i) where both loci had no effect on fitness
      and (ii) where they showed heterozygote superiority, but no epistacy.If the
      populations are initially in linkage equilibrium, then the mean value ofD remains
      zero with inbreeding, but the mean ofD (2) increases to a maximum value and
      decreases until fixation is reached at both loci. The tighter the linkage and the
      greater the selection, then the later is the maximum in the mean ofD (2) reached,
      and the larger its value. The correlation of gene frequencies,r, in the
      population of gametes within segregating lines was also studied. It was found
      that, for a range of selection intensities and initial gene frequencies, the mean
      value ofr (2) was determined almost entirely byN c and time, measured
      proportional toN.The implication of these results on observations of linkage
      disequilibrium in natural populations is discussed. 

PMID- 24442308
TI  - Simulation of models involving mixed selfing and random mating : II. Effects of
      selection and linkage in finite populations.
AB  - The joint effects of linkage, inbreeding, and drift due to finite population size
      were investigated in terms of population changes under selection involving gene
      interaction. Six-locus models with the same amount of recombination between
      adjacent pairs of loci, mixed selfing and random mating, and selection of
      basically three forms (heterotic, optimizing and mixed optimum-heterotic) were
      used for Monte Carlo simulation. The results were primarily described in terms of
      certain measures of gene dispersion, genetic variability, gametic unbalance
      (linkage disequilibrium) and the approach to stable gene frequency equilibria.
      Under both cumulative and diminutive heterosis models, a steady state with
      polymorphisms could be attained with random gene dispersion being small and
      different replicate populations evolved high degrees of gametic unbalance in the
      direction of excess of either coupling or repulsion phase linkages depending on
      the random drift in gene frequencies. Under optimum models, on the other hand,
      all populations approached steady decay toward fixation at all loci although gene
      dispersion was governed by rather complex interactions between the parameters of
      selfing, linkage and selection intensity. Gene dispersion was not necessarily
      proportionately greater with the higher levels of inbreeding. An excess of
      repulsion linkages with mean population fitness approaching unity was noted in
      all runs with the optimum models, more so with tight linkage and heavy
      inbreeding. Any asymmetry in the sense of selection favoring one or the other
      allele tends to reinforce gene fixation particularly under inbreeding.
      Heterozygote advantage, on the other hand, seemed to play a relatively greater
      role under inbreeding in terms of retaining heterozygosity. Mixed optimum
      heterotic models provide a favorable compromise between these conflicting
      attributes of multilocus systems in terms of the maintenance of polymorphisms and
      the maximization of fitness in relation to certain optimal linked gene complexes.
      In general, for moderate to large population size these results are, as expected,
      in line with those reported previously for two-locus deterministic models. 

PMID- 24442309
TI  - Effect of initial linkage disequilibrium and epistasis on fixation probability in
      a small population, with two segregating loci.
AB  - The probability of ultimate fixation was studied for 2 loci small populations by
      the method of Monte Carlo simulation and also partly by analytical treatment. The
      analytical solutions for fixation probability known at present and the difficulty
      of their application to more complex situations were discussed. Monte Carlo
      experiments were carried out for large values ofN e s 1,N e s 2 andN e epsilon,
      for which the analytical solutions have not been obtained.One of the main
      purposes was to investigate the effect of initial linkage disequilibrium (D) on
      fixation probability. Whens 1,s 2 and epsilon are 0, the effect of disequilibrium
      is given by {1-2N e c/(2N e c+1)}D withKIMURA'S model and {1-2N e c/(2 N e c
      c+1)}D with the model ofKARLIN andMCGREGOR. When |N e s 1| and |N e s 2| were
      small and epsilon=0, the effect of disequilibrium was shown to be almost the same
      as in the selectively neutral case (formulas 8). When those parameters are not
      small, the effect of disequilibrium is larger because of the rapid approach to
      fixation.Another purpose of this study was to investigate the effect of epistasis
      on fixation probability.KIMURA obtained the solution for joint fixation ofA andB
      when the selective advantage is given to genotypeAB as the joint effect ofA andB.
      The present study has verified his formula and showed that linkage does not
      affectu(AB) under initial linkage equilibrium. Also some cases of additive *
      additive epistasis were studied. 

PMID- 24442310
TI  - On the fixation of genes of large effects due to continued truncation selection
      in small populations of polygenic systems with linkage.
AB  - The proportion of fixed loci for desirable genes and the time required for
      fixation is studied in simulated diploid populations, which have initially aHARDY
      WEINBERG structure. A symmetric ten-locus system of additive or dominant genes is
      simulated with linkages between adjacent loci varying as .005, .05, or .5. A
      constant degree of upper truncation selection within a population is considered
      over the generations. In different populations the intensity of truncation is
      varied asN/N,N/N+2,N/N+4, ..., whereN is the parental population size, specified
      as 2,4,8 or 16. The selection differential in initial generation, i, thereby
      varies from zero to more than two standard deviations in some cases. The initial
      mean gene frequency,p, simulated in an initial population is .1 or .5.It is
      pointed out that when selective advantage of a gene is large and is changing with
      gene frequency, diffusion approximations assuming constant selective advantage,
      gives higher values for proportion of fixed genes in the case ofp equal to .1 and
      lower values forp equal to .5. With parental population size of 16 or less, a
      relation withN i alone does not give the proportion of fixed genes. Higher order
      terms ofN i appear to be involved in the relation. For the sameN i, the
      proportion is much higher for lowN.The depressing effect of low recombinations
      between loci is of different magnitude for differentN andp for a givenN i. The
      increase in the proportion of fixed genes due to increasingN is not as large when
      pi is low. High intensity of selection offsets considerably the effects of
      population size and linkage when gene effects are large. It appears that with
      increased inbreeding and selection intensity, almost all the genes of large
      effects and at intermediate frequencies can be rapidly fixed regardless of
      linkage.Linkage has been shown to cause faster fixation of genes in the absence
      of selection. With selection, linkage tends to delay fixation. But in the case of
      very low recombinations, there appears to be a level of population size and
      selection intensity, below which there is more rapid fixation because of linkage.
      Selection for dominant genes in the case of very close linkage, delays fixation
      for a number of generations and this delay results in reducing the depressing
      effect of linkage. 

PMID- 24442311
TI  - The role of finite population size and linkage in response to continued
      truncation selection : I. Additive gene action.
AB  - In an attempt to analyse long-term response in finite dioecious populations,
      selection processes are simulated on a computer with situations of parental
      population size, linkages between loci, selection intensity, and heritability,
      specified in a 3(4) factorial design. A diploid polygenic system of 40 loci on 4
      chromosomes is considered for additive genes. Linkage levels are specified as
      free recombinations, adjacent loci 5 map units apart, and as clusters on
      chromosomes with a distance of only .5 units between adjacent loci. Parental
      populations of 8, 16, and 64, truncation selection of 1/2, 1/4, and 1/8 of the
      progeny each generation, and initial heritability of 1, 1/3, and 1/9 are
      simulated for various populations.For these populations, which are initially
      samples from a theoreticalHARDY-WEINBERG situation, it is shown that an initial
      linear phase of response, which may last for only 2 or 3 generations in some
      cases, depends on the intensity of selection alone. The effects and interactions
      of all the above factors on the curvilinearity of response in later generations
      are analysed. It appears that linkages between loci have a strong influence in
      reducing the rate of response and the total response. In the extreme cases of
      gene clusters in a parental population size of 8 with low heritability,
      truncation selection is relatively almost completely ineffective in causing
      change in the mean over generations. The effect of tight linkage is also
      exhibited in causing more reduction in genotypic variance than can be accounted
      for by corresponding response.The depressing effect of finiteness of population
      size on the rate of response and the total response appears to increase in
      geometric proportion with linkages between loci. The number of generations to
      fixation appears to be reduced in a similar manner. A strong interaction between
      population size and linkage is thereby found in various analyses. With parental
      populations as large as 64, linkage effects on response are negligible when
      recombinations between adjacent loci are .05 or more. In such situations there is
      a slower rate of response in later generations with linkage but the total
      response attained and the rate of fixation of inferior genes is about the same as
      for free recombinations. Increase in the intensity of selection appears to
      augment the effects of linkage in reducing the rate of response in later
      generations. This type of interaction is attributed to the accumulation of
      gametic disequilibria due to selection which are retained in the population over
      generations with linkage. 

PMID- 24442312
TI  - The role of finite population size and linkage in response to continued
      truncation selection : II. Dominance and overdominance.
AB  - In a direct Monte Carlo study, the effects and interactions of parental
      population size, close linkages between loci, degree of truncation selection and
      environmental variance are explored in the cases of complete dominance and
      overdominance with equilibrium gene frequency of .5. The base population
      simulated has a gene frequency of .5 at all 40 loci and is a state of gametic
      equilibrium. Response and fixation of genes are studied up to 30 generations.In
      the case of complete dominance of desirable genes, long term response is
      described in terms of an initial phase of change and a later phase when there is
      a very slow approach to the limit and plateaus are established in the case of
      close linkages between loci. The changes in the initial phase consitutes most of
      the total response. Increased selection in parental populations of 16 or less is
      ineffective when recombination value between adjacent loci is as low as .005.
      Linkage effects in reducing response appear to increase in geometric proportions
      with restricted population size.Results of the overdominance model provide an
      interesting study of the effects of population size and linkage on heterozygosity
      while there is selection for the heterozygotes. These effects are partially
      explainable in terms of differences in heterozygosity between chromosomes and
      heterozygosity within chromosomes. The between chromosome component of
      heterozygosity appears to be rapidly reduced with finite population size and
      common heterozygosity within chromosomes is conserved due to linkages between
      loci. In general, however, the effects of selection pressure, linkage and
      population size interact strongly. With small populations and tight linkage,
      increased selection pressure causes a decrease in amount of fixation. With the
      largest population increased selection pressure tends to increase the amount of
      fixation. It is clear, however, that these conclusions must be regarded
      tentatively, and an exact picture of what is happening will be obtained only with
      very extensive simulation. It seems quite clear, also, that single locus finite
      population theory is essentially ineffective. 

PMID- 24442313
TI  - How does outcome-based funding affect service delivery? An analysis of
      consequences within employment services for people living with serious mental
      illness.
AB  - This paper explores the impact of outcome-based funding on service delivery
      within employment services for people with serious mental illness. It draws on a
      case study of a policy change in the provincial disability support program in
      Ontario, Canada where funding for employment programs and services was changed
      from a fee-for-service to an outcome-based model. The findings highlight that the
      financial imperative for programs to meet employment targets in order to secure
      their funding has shifted the focus away from the provision of pre-employment
      supports to job development and job placements. However, there remains little
      attention to job matching and career development, and there is concern about
      access to services among those with complex barriers to employment. There is a
      need to reconcile tensions between the goals of outcome-based funding and on-the
      ground service delivery to promote ongoing innovation in employment services for
      people with serious mental illness. 

PMID- 24442314
TI  - A non-ionic surfactant reduces the induction time and enhances expression levels
      of bubaline somatotropin in Pichia pastoris.
AB  - This study describes a simple approach for enhanced secretory expression of
      bubaline somatotropin (BbST) in the methylotropic yeast Pichia pastoris. A Mut(s)
      Pichia transformant carrying multi-copy, non-codon optimized BbST cDNA sequence,
      expressed and secreted the recombinant protein into the culture medium to a level
      of 25 % of the total proteins in the culture supernatant, after 120 h of
      induction. Inclusion of polysorbate-80 in the inducing medium resulted in a
      significant improvement in the BbST expression (up to 45 % of the total culture
      supernatant proteins) with concomitant reduction in the induction time to 48 h.
      The amount of BbST obtained was 148 mg/L, which was around fivefold higher than
      that obtained without the surfactant. BbST was purified to near homogeneity by
      FPLC on Q-sepharose FF anion-exchange column. Protein authenticity was judged by
      SDS-PAGE and western blot analyses. A bioassay based on proliferation of Nb2 rat
      lymphoma cell lines confirmed that the purified, recombinant BbST is biologically
      active. Use of polysorbate-80 in combination with methanol, during the induction
      phase, is likely to have general applicability in lowering the induction time and
      enhancing the secretory expression of other commercially important proteins in
      Mut(s) strains of P. pastoris. 

PMID- 24442315
TI  - Signatures of selection in five Italian cattle breeds detected by a 54K SNP
      panel.
AB  - In this study we used a medium density panel of SNP markers to perform population
      genetic analysis in five Italian cattle breeds. The BovineSNP50 BeadChip was used
      to genotype a total of 2,935 bulls of Piedmontese, Marchigiana, Italian Holstein,
      Italian Brown and Italian Pezzata Rossa breeds. To determine a genome-wide
      pattern of positive selection we mapped the F st values against genome location.
      The highest F st peaks were obtained on BTA6 and BTA13 where some candidate genes
      are located. We identified selection signatures peculiar of each breed which
      suggest selection for genes involved in milk or meat traits. The genetic
      structure was investigated by using a multidimensional scaling of the genetic
      distance matrix and a Bayesian approach implemented in the STRUCTURE software.
      The genotyping data showed a clear partitioning of the cattle genetic diversity
      into distinct breeds if a number of clusters equal to the number of populations
      were given. Assuming a lower number of clusters beef breeds group together. Both
      methods showed all five breeds separated in well defined clusters and the
      Bayesian approach assigned individuals to the breed of origin. The work is of
      interest not only because it enriches the knowledge on the process of evolution
      but also because the results generated could have implications for selective
      breeding programs. 

PMID- 24442316
TI  - Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells
      in acute liver injured mice.
AB  - Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of
      diseases including liver injury, the current study aims to investigate the
      protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute
      injury liver and related action mechanisms. The mice were injected
      intraperitoneally with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). 39
      male BABL/c mice were randomly divided into four groups: normal control, model
      control, CMCS treatment and 1,10-phenanthroline treatment groups. The Serum liver
      function parameters including alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels were assayed with the commercial kit. The
      inflammation and scaffold structure in liver were stained with hematoxylin and
      eosin and silver staining respectively. The LSECs and sub-endothelial basement
      membrane were observed with the scanning and transmission electronic microscope.
      The protein expressions of intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1) in liver were analyzed with Western
      blotting. Expression of von Willebrand factor (vWF) was investigated with
      immunofluorescence staining. The lipid peroxidation indicators including
      antisuperoxideanion (ASAFR), hydroxyl free radical (.OH), superoxide dismutase
      (SOD), malondialdehyde and glutathione S-transferase (GST) were determined with
      kits, and matrix metalloproteinase-2 and 9 (MMP-2/9) activities in liver were
      analyzed with gelatin zymography and in situ fluorescent zymography respectively.
      The model mice had much higher serum levels of ALT and AST than the normal mice.
      Compared to that in the normal control, more severe liver inflammation and
      hepatocyte apoptosis, worse hepatic lipid peroxidation demonstrated by the
      increased ASAFR, .OH and MDA, but decreased SOD and GST, increased MMP-2/9
      activities and VCAM-1, ICAM-1 and vWF expressions, which revealed obvious LSEC
      injury and scaffold structure broken, were shown in the model control. Compared
      with the model group, CMCS and 1,10-phenanthroline significantly improved serum
      ALT/AST, attenuated hepatic inflammation and improved peroxidative injury in
      liver, decreased MMP-2/9 activities in liver tissue, improved integration of
      scaffold structure, and decreased protein expression of VCAM-1 and ICAM-1. CMCS
      could protect LSECs from injury and maintain the microvasculature integration in
      acute injured liver of mice induced by LPS/D-GalN. Its action mechanism was
      associated with the down-regulation of MMP-2/9 activities and inhibition of
      peroxidation in injured liver. 

PMID- 24442317
TI  - NAT2 slow acetylation genotypes contribute to asthma risk among Caucasians:
      evidence from 946 cases and 1,091 controls.
AB  - NAT2 plays a critical role in external chemical detoxification. Thus,
      polymorphism of NAT2 has been suggested to associate with several disorders. A
      number of studies have been devoted to the relationship between NAT2 polymorphism
      and asthma risk. However, the results were inconclusive. In this study we aimed
      to derive a more precise estimation of the association. A literature search in
      the common databases was conducted and then meta-analyses evaluating the
      association of NAT2 polymorphism and asthma risk were performed. Eligible studies
      were identified for the period up to May 2013. A total of five case-control
      studies containing 946 cases and 1,091 controls were lastly included for
      analysis. The overall data showed that slow acetylators of NAT2 might have an
      association with increased asthma risk (OR 2.20; 95% CI 1.31-3.72). The pooled
      data suggest that slow acetylators of NAT2 might contribute to asthma risk among
      Caucasians. Future studies are needed to confirm this conclusion.

PMID- 24442318
TI  - Clodronate liposomes reduce excessive scar formation in a mouse model of burn
      injury by reducing collagen deposition and TGF-beta1 expression.
AB  - Clodronate liposome injection is an effective approach to selectively and
      specifically depleting macrophages. Macrophages play a crucial role in cutaneous
      wound healing and are associated with excessive scar formation. Use of clodronate
      liposomes to enhance cutaneous wound healing and reduce scar formation could
      represent a major advance in wound therapy and hypertrophic scar treatment. This
      study aimed to investigate the effects of subcutaneous or intraperitoneal
      injection of clodronate liposomes on cutaneous wound healing and scar formation.
      A burn injury mouse model was used. Mice were treated with subcutaneous or
      intraperitoneal injection of clodronate liposomes. Wound healing time was
      analyzed and scar tissues were harvested for hematoxylin and eosin (HE) staining,
      reverse transcription polymerase chain reaction (RT-PCR) and Western blot
      analyses. Wound healing time in treated mice was extended. HE showed that the
      basal layer of the epidermis in treated scars was flattened, the dermis layer was
      not significantly thickened, and collagen fibers were well arranged, with few
      cells and micro vessels. RT-PCR and Western blot analyses showed that the levels
      of TGF-beta1 and collagen I-alpha2 were decreased in treated mice. Clodronate
      liposomes reduce excessive scar formation and delay cutaneous wound healing
      possibly by reducing collagen deposition and macrophage-derived TGF-beta1
      expression.

PMID- 24442319
TI  - Differentially expressed genes in response to gamma-irradiation during the
      vegetative stage in Arabidopsis thaliana.
AB  - Biochemical and physiological processes in plants are affected by gamma
      irradiation, which causes significant changes in gene transcripts and expression.
      To identify the differentially expressed Arabidopsis genes in response to gamma
      irradiation, we performed a microarray analysis with rosette leaves during the
      vegetative stage. Arabidopsis plants were exposed to a wide spectrum doses of
      gamma ray (100, 200, 300, 400, 800, 1200, 1600 or 2000 Gy) for 24 h. At the dose
      range from 100 to 400 Gy, irradiated plants were found to be shorter than
      controls after 8 days of irradiation, while doses over 800 Gy caused severe
      growth retardation. Therefore, 100 and 800 Gy were selected as adequate doses for
      microarray analysis to identify differentially expressed genes. Among the 20,993
      genes used as microarray probes, a total number of 496 and 1,042 genes were up
      regulated and down-regulated by gamma-irradiation, respectively (P < 0.05). We
      identified the characteristics of the genes that were up-and down-regulated
      fourfold higher genes by gamma irradiation according to The arabidopsis
      information resource gene ontology. To confirm the microarray results, we
      performed a northern blot and quantitative real-time PCR with several selected
      genes that had a large difference in expression after irradiation. In particular,
      genes associated with lipid transfer proteins, histones and transposons were down
      regulated by 100 and/or 800 Gy of gamma irradiation. The expression patterns of
      selected genes were generally in agreement with the microarray results, although
      there were quantitative differences in the expression levels.

PMID- 24442320
TI  - Cofactor analogue-induced chemical reactivation of endonuclease activity in a DNA
      cleavage/methylation deficient TspGWI N473A variant in the NPPY motif.
AB  - We reported previously that TspGWI, a prototype enzyme of a new Thermus sp.
      family of restriction endonucleases-methyltransferases (REases-MTases), undergoes
      the novel phenomenon of sinefungin (SIN)-caused specificity transition. Here we
      investigated mutant TspGWI N473A, containing a single amino acid (aa)
      substitution in the NPPY motif of the MTase. Even though the aa substitution is
      located within the MTase polypeptide segment, DNA cleavage and modification are
      almost completely abolished, indicating that the REase and MTase are intertwined.
      Remarkably, the TspGWI N473A REase functionality can be completely reconstituted
      by the addition of SIN. We hypothesize that SIN binds specifically to the enzyme
      and restores the DNA cleavage-competent protein tertiary structure. This
      indicates the significant role of allosteric effectors in DNA cleavage in Thermus
      sp. enzymes. This is the first case of REase mutation suppression by an S
      adenosylmethionine (SAM) cofactor analogue. Moreover, the TspGWI N473A clone
      strongly affects E. coli division control, acting as a 'selfish gene'. The mutant
      lacks the competing MTase activity and therefore might be useful for applications
      in DNA manipulation. Here we present a case study of a novel strategy for REase
      activity/specificity alteration by a single aa substitution, based on the
      bioinformatic analysis of active motif locations, combining (a) aa sequence
      engineering (b) the alteration of protein enzymatic properties, and (c) the use
      of cofactor-analogue cleavage reconstitution and stimulation.

PMID- 24442321
TI  - Electrophysiologic evaluation of retinal function in patients with psoriasis and
      vitiligo.
AB  - PURPOSE: To investigate the relation between psoriasis and vitiligo with the
      electrophysiologic function of the retinal photoreceptors. METHODS: Patients with
      psoriasis or vitiligo referred for PUVA therapy were enrolled. Complete eye
      examination was performed. Patients with any drug or familial history or abnormal
      eye examination that might affect the retinal function were excluded.
      Standardized full-field electroretinogram (ERG) elicited with Ganzfeld stimuli
      using the commercial ERG system (Retiport32; Roland Consult) according to
      International Society for Clinical Electrophysiology of Vision guidelines was
      performed. The outcome measures were the difference between the mean rod
      response, standard combined response, single-flash cone response and 30-Hz
      flicker wave amplitudes of the patients and normal population. RESULTS: Seventy
      six eyes of 38 patients (vitiligo: 21; psoriasis: 17) and 40 eyes of 20 normal
      subjects were enrolled in this study. The mean age of patients was 31.3 +/- 11.3
      years (range 16-54 years). Twenty-two patients (58 %) were female. The mean rod
      response b-wave, standard combined a- and b-waves, single-flash cone response b
      wave and the 30-Hz flicker (N1-P1) amplitudes were significantly lower than the
      normal population in the same range of age as the study group. There was no
      significant difference between the patients with vitiligo and those with
      psoriasis in all wave amplitudes (P = 0.094). CONCLUSION: This study showed that
      overall retinal electrophysiologic function in patients with vitiligo or
      psoriasis is significantly impaired compared with normal population, independent
      of age and sex.

PMID- 24442322
TI  - The role of mTORC1 in regulating protein synthesis and skeletal muscle mass in
      response to various mechanical stimuli.
AB  - Skeletal muscle plays a fundamental role in mobility, disease prevention, and
      quality of life. Skeletal muscle mass is, in part, determined by the rates of
      protein synthesis, and mechanical loading is a major regulator of protein
      synthesis and skeletal muscle mass. The mammalian/mechanistic target of rapamycin
      (mTOR), found in the multi-protein complex, mTORC1, is proposed to play an
      essential role in the regulation of protein synthesis and skeletal muscle mass.
      The purpose of this review is to examine the function of mTORC1 in relation to
      protein synthesis and cell growth, the current evidence from rodent and human
      studies for the activation of mTORC1 signaling by different types of mechanical
      stimuli, whether mTORC1 signaling is necessary for changes in protein synthesis
      and skeletal muscle mass that occur in response to different types of mechanical
      stimuli, and the proposed molecular signaling mechanisms that may be responsible
      for the mechanical activation of mTORC1 signaling. 

PMID- 24442323
TI  - Ultrastructural studies of the aggregation and fusion of plant protoplasts.
AB  - Electron microscopy has been used to assess the efficiency of four different
      techniques as potential methods for fusing isolated plant protoplasts. Protoplast
      aggregation has been achieved by the use of an antiserum, high pH, polyethylene
      glycol 6000 or poly-L-lysine. The ultrastructural characteristics of each
      treatment are described. Fusion of adjacent surface membranes does not
      necessarily fellow aggregation, and has not been observed in protoplasts
      aggregated by antisera. The other three methods all result in some degree of
      fusion, depending upon the state of the protoplasts and the temperature of the
      experiment. Fusion is favoured by a high density of cytoplasm in the protoplasts
      and by higher temperatures. The methods are discussed in terms of their likely
      applicability as a practical fusion technique. 

PMID- 24442324
TI  - The Pasteur effect in carrot root tissue.
AB  - The presence of a Pasteur effect in aged discs of carrot (Daucus carota L.)
      storage tissue and its apparent absence in fresh discs was confirmed. Changes in
      the concentration of glycolytic intermediates have been determined, following the
      transfer of fresh and aged discs from air to nitrogen. In addition the changes in
      glycolytic intermediates associated with the ageing of the discs have also been
      measured. The results are analysed and interpreted to indicate that in aged discs
      the enzyme phosphofructokinase plays an important role in controlling glycolysis.
      In fresh discs phosphofructokinase appears to exert little control of glycolysis.
      The results also suggest that glycolysis may be controlled at points other than
      phosphofructokinase. 

PMID- 24442325
TI  - The control of glycolysis in aged slices of carrot root tissue.
AB  - The possibility that the rate of glycolysis in aged slices of carrot (Daucus
      carota L.) is controlled by the enzyme phosphofructokinase was examined, by
      changing the rate of metabolism, by supplying the tissue with potassium chloride,
      potassium phosphate and potassium citrate and measuring the subsequent changes in
      levels of metabolites. Potassium chloride and potassium phosphate stimulate
      glycolysis, potassium citrate inhibits glycolysis and the associated changes in
      metabolites are consistent with the view that respiration is controlled by a dual
      system involving phosphofructokinase and glyceraldehyde phosphate dehydrogenase
      or possibly phosphoglycerate kinase. It is proposed that the control points are
      interlocked by phosphoenolpyruvate and phosphoglycerate. Thus if glyceraldehyde
      phosphate dehydrogenase is activated leading to an accumulation of
      phosphoglycerate and phosphoenolpyruvate, these compounds will inhibit
      phosphofructokinase. Thus our proposal for metabolic control in carrot resembles
      those proposed in mammalian systems except that the negative feedback system
      involving ATP and AMP which controls phosphofructokinase in mammals is replaced
      by a negative feedback system involving phosphoenolpyruvate and phosphoglycerate.

PMID- 24442326
TI  - The specificity of auxin transport in intact pea seedlings (Pisum sativum L.).
AB  - When eight (14)C-labelled auxin and non-auxin compounds were applied to the
      apical buds of intact dwarf pea seedlings (Pisum sativum L.), only [1
      (14)C]indoleacetic acid ([(14)C]IAA) and alpha-[1-(14)C] naphthaleneacetic acid
      ([(14)C]NAA) underwent appreciable basipetal transport during the first 24 h;
      over a longer period (72 h) considerable basipetal transport of the auxin [1
      (14)C]2,4-dichlorophenoxyacetic acid ([(14)C]2,4-D) also occurred, but at a very
      much lower velocity (ca. 1.4-2.2 mm.h(-1)). The movement of 2,4-D possessed many
      of the characteristics of a typical auxin transport. During uptake and transport
      IAA and NAA were extensively metabolised to the corresponding aspartates, and to
      ethanol-insoluble/NaOH-soluble compounds; little metabolism of 2,4-D was
      observed. None of the non-auxin compounds applied (sorbose, sucrose, leucine,
      adenine and kinetin) underwent appreciable basipetal transport from the apical
      bud. All but sorbose were extensively metabolised by the apical tissues. Little
      metabolism of sorbose itself was detected.The results suggest that the long
      distance basipetal auxin transport system from the apical bud of intact plants is
      specific for auxins; the specificity may result from the affinity of auxins for
      specific transport sites. 

PMID- 24442327
TI  - Chloroplast and cytoplasmic enzymes : V. Pea-leaf carbonic anhydrases.
AB  - Chloroplastic and cytoplasmic forms of pea (Pisum sativum L.) leaf carbonic
      anhydrase were separated by isoelectric focusing. The two forms have identical pH
      optima, 7.0 for the hydration reaction and 7.5 for the dehydration reaction, and
      identical Michaelis constants for CO2, 0.03 M. Neither isozyme is affected by any
      of several compounds involved in carbon metabolism in the green plant. 

PMID- 24442328
TI  - Evidence against the occurrence of adenosine-3':5'-cyclic monophosphate in higher
      plants.
AB  - Previous reports on the incorporation of [(14)C]adenine into adenosine-3':5'
      cyclic monophosphate (cyclic AMP) in oat (Avena sativa L.) and maize (Zea mays
      L.) coleoptile sections, chick-pea (Cicer arietinum L.) embryos and barley
      (Hordeum vulgare L.) aleurone layers were reexamined. Separation of labelled
      nucleotides on DEAE-Sephadex A 25 showed that a peak of (14)C activity,
      previously considered to be cyclic AMP, is not identical with this compound.
      Attempts to detect the cyclic nucleotide by means of a highly specific protein
      kinase assay in various plant tissues (Nicotiana tabacum L., tissue culture;
      Catharanthus roseus Don., tissue culture; Lycopersicon esculentum Mill,
      seedlings; Nicotiana tabacum, pith parenchyma; Avena sativa, coleoptiles) failed
      even though up to 100 g of plant material was extracted and a number of control
      experiments were carried out to insure that cyclic AMP, if present in the
      extracts, could be measured. 

PMID- 24442329
TI  - [C4-Pathway of photosynthesis in the blue-green alga Anacystis nidulans].
AB  - CO2 exchange, (14)CO2 fixation and radioactive photosynthetic products of
      Anacystis nidulans (strain L 1402-1) were studied during the induction period at
      +30 degrees  C. The algae were grown at +35 degrees  C in an atmosphere of 0.03
      or 3.0 vol.-% CO2 and were measured under conditions of low CO2 concentrations.
      At the beginning of the photosynthetic period (14)CO2 was mainly incorporated
      into aspartate and glutamate. The patterns of labelling are very similar to those
      of the C4 pathway of photosynthesis. alpha-Hydroxypyridylmethane-sulfonic acid
      (10(-5) M) and isonicotinyl hydrazide (10(-2) M) have only a small effect on the
      percentage distribution of labelled products. The activities of glycolate
      dehydrogenase, ribulose-1,5-diphosphate carboxylase and phosphoenolpyruvate
      carboxylase, measured in crude extracts of Anacystis, were inhibited by alpha
      hydroxypyridylmethane-sulfonic acid and dichlorophenyldimethyl urea.In other
      series of experiments the pattern of (14)C incorporation from asparate was
      investigated. Radioactivity from [(14)C]aspartate was mainly incorporated into
      glutamate, alanine, theronine, isoleucine and glycine/serine. Enzyme activities
      of citrate synthase, aconitate hydratase, isocitrate dehydrogenase and glutamate
      dehydrogenase were relatively low in CO2-grown Anacystis cells compared to those
      in air grown cells. The obtained results are discussed, with reference to the
      operation of the C4 pathway of photosynthesis and reductive carboxylation of
      succinate to glutamate in Anacystis. 

PMID- 24442330
TI  - Non-stationarity of EEG during wakefulness and anaesthesia: advantages of EEG
      permutation entropy monitoring.
AB  - Monitors evaluating the electroencephalogram (EEG) to determine depth of
      anaesthesia use spectral analysis approaches for analysis windows up to 61.5 s as
      well as additional smoothing algorithms. Stationary EEG is required to reliably
      apply the index algorithms. Because of rapid physiological changes, artefacts,
      etc., the EEG may not always fulfil this requirement. EEG analysis using
      permutation entropy (PeEn) may overcome this issue, since PeEn can also be
      applied to practically nonstationary EEG. One objective was to determine the
      duration of EEG sequences that can be considered stationary at different
      anaesthetic levels. The second, more important objective was to test the
      reliability of PeEn to reflect the anaesthetic levels for short EEG segments. EEG
      was recorded from 15 volunteers undergoing sevoflurane and propofol anaesthesia
      at different anaesthetic levels and for each group 10 data sets were included.
      EEG stationarity was evaluated for EEG sample lengths from 4 to 116 s for each
      level. PeEn was calculated for these sequences using different parameter settings
      and analysis windows from 2 to 60 s. During wakefulness EEG can only be
      considered stationary for sequences up to 12 s. With increasing anaesthetic level
      the probability and duration of stationary EEG increases. PeEn is able to
      reliably separate consciousness from unconsciousness for EEG segments as short as
      2 s. Especially during wakefulness a conflict between stationary EEG sequence
      durations and methods used for monitoring may exist. PeEn does not require
      stationarity and functions for EEG sequences as short as 2 s. These promising
      results seem to support the application of non-linear parameters, such as PeEn,
      to depth of anaesthesia monitoring. 

PMID- 24442331
TI  - Evidence-based medicine and the hard problem of multimorbidity.

PMID- 24442332
TI  - A framework for crafting clinical practice guidelines that are relevant to the
      care and management of people with multimorbidity.
AB  - Many patients of all ages have multiple conditions, yet clinicians often lack
      explicit guidance on how to approach clinical decision-making for such people.
      Most recommendations from clinical practice guidelines (CPGs) focus on the
      management of single diseases, and may be harmful or impractical for patients
      with multimorbidity. A major barrier to the development of guidance for people
      with multimorbidity stems from the fact that the evidence underlying CPGs derives
      from studies predominantly focused on the management of a single disease. In this
      paper, the investigators from the Improving Guidelines for Multimorbid Patients
      Study Group present consensus-based recommendations for guideline developers to
      make guidelines more useful for the care of people with multimorbidity. In an
      iterative process informed by review of key literature and experience, we drafted
      a list of issues and possible approaches for addressing important coexisting
      conditions in each step of the guideline development process, with a focus on
      considering relevant interactions between the conditions, their treatments and
      their outcomes. The recommended approaches address consideration of coexisting
      conditions at all major steps in CPG development, from nominating and scoping the
      topic, commissioning the work group, refining key questions, ranking importance
      of outcomes, conducting systematic reviews, assessing quality of evidence and
      applicability, summarizing benefits and harms, to formulating recommendations and
      grading their strength. The list of issues and recommendations was reviewed and
      refined iteratively by stakeholders. This framework acknowledges the challenges
      faced by CPG developers who must make complex judgments in the absence of high
      quality or direct evidence. These recommendations require validation through
      implementation, evaluation and refinement. 

PMID- 24442333
TI  - Multimorbidity and evidence generation.
AB  - Most people with a chronic disease actually have more than one, a condition known
      as multimorbidity. Despite this, the evidence base to prevent adverse disease
      outcomes has taken a disease-specific approach. Drawing on a conference,
      Improving Guidelines for Multimorbid Patients, the goal of this paper is to
      identify challenges to the generation of evidence to support the care of people
      with multimorbidity and to make recommendations for improvement. We identified
      three broad categories of challenges: 1) challenges to defining and measuring
      multimorbidity; 2) challenges related to the effects of multimorbidity on study
      design, implementation and analysis; and 3) challenges inherent in studying
      heterogeneity of treatment effects in patients with differing comorbid
      conditions. We propose a set of recommendations for consideration by
      investigators and others (reviewers, editors, funding agencies, policymaking
      organizations) involved in the creation of evidence for this common type of
      person that address each of these challenges. The recommendations reflect a
      general approach that emphasizes broader inclusion (recruitment and retention) of
      patients with multimorbidity, coupled with more rigorous efforts to measure
      comorbidity and comorbidity burden and the influence of multimorbidity on
      outcomes and the effects of therapy. More rigorous examination of heterogeneity
      of treatment effects requires careful attention to prioritizing the most
      important comorbid-related questions, and also requires studies that provide
      greater statistical power than conventional trials have provided. Relatively
      modest changes in the orientation of current research along these lines can be
      helpful in pointing to and partially addressing selected knowledge gaps. However,
      producing a robust evidence base to support patient-centered decision making in
      complex individuals with multimorbidity, exposed to many different combinations
      of potentially interacting factors that can modify the risks and benefits of
      therapies, is likely to require a clinical research enterprise fundamentally
      restructured to be more fully integrated with routine clinical practice. 

PMID- 24442335
TI  - The ninety-nine percent: focusing on the patient to reduce readmissions.

PMID- 24442334
TI  - Addressing multimorbidity in evidence integration and synthesis.
AB  - To minimize bias, clinical practice guidelines (CPG) for managing patients with
      multiple conditions should be informed by well-planned syntheses of the totality
      of the relevant evidence by means of systematic reviews and meta-analyses.
      However, deficiencies along the entire evidentiary pathway hinder the development
      of evidence-based CPGs. Published reports of trials and observational studies
      often do not provide usable data on treatment effect heterogeneity, perhaps
      because their design, analysis and presentation is seldom geared towards
      informing on how multimorbidity modifies the effect of treatments. Systematic
      reviews and meta-analyses inherit all the limitations of their building blocks
      and introduce additional of their own, including selection biases at the level of
      the included studies, ecological biases, and analytical challenges. To generate
      recommendations to help negotiate some of the challenges in synthesizing the
      primary literature, so that the results of the evidence synthesis is applicable
      to the care of those with multiple conditions. Informal group process. We have
      built upon established general guidance, and provide additional recommendations
      specific to systematic reviews that could improve the CPGs for multimorbid
      patients. We suggest that following the additional recommendations is good
      practice, but acknowledge that not all proposed recommendations are of equal
      importance, validity and feasibility, and that further work is needed to test and
      refine the recommendations. 

PMID- 24442336
TI  - [Corrigendum] Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos
      usambarensis, with potential anti-tumor activity against apoptosis-resistant
      cancer cells.
AB  - After the publication of the article, the authors noted that they had made an
      error regarding certain data in their manuscript. The error relates to the
      statistical analysis performed for the data illustrated in Fig. 4A: On page 963
      of our article, line 17 of the left-handed column, we identified an erroneous
      statistical result with respect to the data illustrated in Fig. 4A. The initial
      statistical value of 'p<0.01' must be corrected to '(p=0.06 when compared to
      control; Fig. 4A)'.

PMID- 24442337
TI  - Predictive value of the corrected TIMI frame count in patients with suspected
      angina pectoris but no obstructive coronary artery disease at angiography.
AB  - AIMS: To evaluate whether the corrected thrombolysis in myocardial infarction
      frame count (CTFC), an index of resting coronary blood flow, is associated with
      the risk of major adverse cardiovascular events (MACE) in patients with suspected
      stable angina pectoris (SAP) but no obstructive coronary artery disease (CAD) at
      angiography. METHODS AND RESULTS: In this case-control study, CTFC at baseline in
      127 patients (50 % women) who subsequently experienced a myocardial infarction,
      non-hemorrhagic stroke or cardiovascular death during 2001-2011 was compared with
      CTFC in 254 event-free matched controls. All patients had suspected SAP but no
      obstructive (>=50 % stenosis) CAD at baseline angiography. Mean CTFC in controls
      was 23.4 (95 % confidence interval 20.9-25.9) frames and mean CTFC in cases did
      not differ significantly with a difference of -1.0 (-3.1 to 1.1) frames (P =
      0.35) and no sex-specific interaction (P = 0.18). In a conditional logistic
      regression model, we found no dose-response relationship between CTFC and the
      risk of MACE, i.e., compared to the risk in the lowest CTFC quintile, the odds
      ratios for MACE were 1.3 (0.7-2.6), 0.7 (0.3-1.3), 0.7 (0.4-1.5) and 1.0 (0.5
      2.1) in the second, third, fourth and fifth CTFC quintiles, respectively.
      Adjustment for cardiac risk factors including diabetes, active smoking, body mass
      index, and use of lipid-lowering and antihypertensive medication did not
      significantly change the results. CONCLUSIONS: In patients with SAP symptoms
      without obstructive CAD at angiography, CTFC is not associated with the risk of
      MACE.

PMID- 24442338
TI  - Contrast-enhanced voiding urosonography with intravesical administration of a
      second-generation ultrasound contrast agent for diagnosis of vesicoureteral
      reflux: prospective evaluation of contrast safety in 1,010 children.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the safety of intravesical administration
      of a second-generation ultrasound (US) contrast agent for the diagnosis of
      vesicoureteral reflux in children. MATERIALS AND METHODS: One thousand and ten
      children (563 girls, 447 boys; mean age: 2.9 years, range: 15 days-17.6 years)
      with 2,043 pelvi-ureter-units underwent contrast-enhanced voiding urosonography
      (ce-VUS) to rule out vesicoureteral reflux. A second-generation US contrast agent
      (SonoVue(r), Bracco, Milan) was administered intravesically through transurethral
      bladder catheterization at a dose of 0.5 ml/bladder filling. Possible adverse
      events were monitored during the examination and followed up for 7 days after ce
      VUS by phone calls. Urine analysis and culture were performed 3-5 days before ce
      VUS in all children and 24-48 h in any patient who reported with adverse events.
      RESULTS: No case of serious adverse event was recorded. Minor events were
      reported in 37 children (3.66% of the study population). These included dysuria
      (n = 26, 2.57%), urinary retention (n = 2, 0.2%), abdominal pain (n = 2, 0.2%),
      anxiety (n = 1, 0.1%) and crying (n = 1, 0.1%) during micturition, blood and
      mucous discharge (n = 1, 0.1%), increased frequency of micturition (n = 1, 0.1%),
      vomiting (n = 1, 0.1%), perineal irritation (n = 1, 0.1%), and an episode of
      urinary tract infection 10 days after ce-VUS (n = 1, 0.1%). Of these adverse
      events, 91.9% were subacute in onset and 8.1% were delayed. All events were self
      limited and none required hospitalization. CONCLUSION: There were no serious
      adverse events. Only a few minor events were reported, most likely due to the
      catheterization process. Thus, ce-VUS with intravesical administration of the
      second-generation US contrast agent (SonoVue(r)) for vesicoureteral reflux
      detection or exclusion had a favorable safety profile in our study group.

PMID- 24442339
TI  - Maintenance of whole-body therapeutic hypothermia during patient transport and
      magnetic resonance imaging.
AB  - Therapeutic hypothermia has become standard treatment for neonatal hypoxic
      ischemic encephalopathy (HIE), with brain MRI commonly performed after the child
      has been rewarmed. However, early imaging during hypothermia might provide
      information important in designing clinical trials that refine and personalize
      therapeutic hypothermia. We tested a protocol to ensure safety and maintenance of
      hypothermia during in-hospital transport and MRI. MRI during therapeutic
      hypothermia was performed in 13 newborns on the 2nd-3rd postnatal days. Mean one
      way transport time was 20.0 +/- 3.3 min. Mean rectal temperatures ( degrees C)
      leaving the unit, upon arrival at the MR suite, during MRI scan and upon return
      to the unit were 33.5 +/- 0.3  degrees C, 33.3 +/- 0.3  degrees C, 33.1 +/- 0.4 
      degrees C and 33.4 +/- 0.3  degrees C, respectively. Using our protocol
      therapeutic hypothermia was safely and effectively continued during in-hospital
      transport and MRI without adverse effects.

PMID- 24442340
TI  - MRI for clinically suspected pediatric appendicitis: case interpretation.
AB  - As utilization of MRI for clinically suspected pediatric appendicitis becomes
      more common, there will be increased focus on case interpretation. The purpose of
      this pictorial essay is to share our institution's case interpretation
      experience. MRI findings of appendicitis include appendicoliths, tip
      appendicitis, intraluminal fluid-debris level, pitfalls of size measurements, and
      complications including abscesses. The normal appendix and inguinal appendix are
      also discussed. 

PMID- 24442341
TI  - Improving pediatric radiology in India.
AB  - BACKGROUND: India had a population of 1,259,271,000 in 2012, with 31% of its
      population composed of children younger than 15 years. In comparison, children
      younger than 15 compose 20% of the population in the United States and 16% in
      Canada. Despite the differences in this demographic, little emphasis is placed on
      pediatric radiology in India. OBJECTIVE: To conduct a needs assessment evaluating
      the adequacy of pediatric radiology in India and to establish a pediatric
      radiology education program in India. MATERIALS AND METHODS: We developed a
      questionnaire to assess radiologists' perspective on the quality of training in
      pediatric radiology. Responses were obtained from attendees at a pediatric
      radiology education program in Mumbai. These data were used to obtain funding and
      implement a program to increase awareness and stimulate pediatric radiology
      training at select institutions across India. RESULTS: Out of 86 respondents, 82%
      indicated that their academic institutions did not place emphasis on dedicated
      pediatric radiology training, and 63% indicated they received less than 2 weeks
      of dedicated training. Of the respondents, 77% said their institutions practiced
      pediatric radiology with inadequate standard of care and 75% of respondents said
      pediatric radiology would gain increasing importance in the future. Outcomes of
      the implemented program included increased awareness of pediatric radiology and
      establishment of a pediatric radiology fellowship program in India. CONCLUSION:
      Education and training in pediatric radiology in India is inadequate. Focused
      initiatives have the potential to improve the standards set for pediatric
      radiology in India. Similar initiatives could help develop pediatric radiology in
      other developing countries.

PMID- 24442343
TI  - Increased progesterone receptor A expression in labouring human myometrium is
      associated with decreased promoter occupancy by the histone demethylase JARID1A.
AB  - Progesterone regulates female reproductive function predominantly through two
      nuclear progesterone receptors (PRs), PR-A and PR-B. During human parturition
      myometrial PR expression is altered to favour PR-A, which activates pro-labour
      genes. We have previously identified histone H3 lysine 4 trimethylation (H3K4me3)
      as an activator of myometrial PR-A expression at labour. To further elucidate the
      mechanisms regulating PR isoform expression in the human uterus at labour, we
      have (i) determined the methylation profile of the cytosine-guanine dinucleotides
      (CpG) island in the promoter region of the PR gene and (ii) identified the
      histone-modifying enzymes that target the H3K4me3 mark at the PR promoters in
      term and preterm human myometrial tissues obtained before and after labour onset.
      Bisulphite sequencing showed that despite overall low levels of PR CpG island
      methylation, there was a significant decrease in methylated CpGs with labour in
      both preterm (P < 0.05) and term (P < 0.01) groups downstream of the PR-B
      transcription start site. This methylation change was not associated with altered
      PR-B expression, but may contribute to the increase in PR-A expression with
      labour. Chromatin immunoprecipitation revealed that the histone
      methyltransferase, SET and MYND domain-containing protein 3 (SMYD3), bound to the
      PR gene at significantly higher levels at the PR-A promoter compared with the PR
      B promoter (P < 0.010), with no labour-associated changes observed. The H3K4
      demethylase, Jumonji AT-rich interactive domain 1A (JARID1A), also bound to the
      PR-A, but not to the PR-B promoter prior to term labour, and decreased
      significantly at the onset of labour (P = 0.014), providing a mechanism for the
      previously reported increase in H3K4me3 level and PR-A expression with labour.
      Our studies suggest that epigenetic changes mediated by JARID1A, SMYD3 and DNA
      methylation may be responsible, at least in part, for the functional progesterone
      withdrawal that precipitates human labour. 

PMID- 24442342
TI  - Patch clamp studies of human sperm under physiological ionic conditions reveal
      three functionally and pharmacologically distinct cation channels.
AB  - Whilst fertilizing capacity depends upon a K(+) conductance (GK) that allows the
      spermatozoon membrane potential (Vm) to be held at a negative value, the
      characteristics of this conductance in human sperm are virtually unknown. We
      therefore studied the biophysical/pharmacological properties of the K(+)
      conductance in spermatozoa from normal donors held under voltage/current clamp in
      the whole cell recording configuration. Our standard recording conditions were
      designed to maintain quasi-physiological, Na(+), K(+) and Cl(-) gradients.
      Experiments that explored the effects of ionic substitution/ion channel blockers
      upon membrane current/potential showed that resting Vm was dependent upon a
      hyperpolarizing K(+) current that flowed via channels that displayed only weak
      voltage dependence and limited (~7-fold) K(+) versus Na(+) selectivity. This
      conductance was blocked by quinidine (0.3 mM), bupivacaine (3 mM) and clofilium
      (50 uM), NNC55-0396 (2 uM) and mibefradil (30 uM), but not by 4-aminopyridine (2
      mM, 4-AP). Progesterone had no effect upon the hyperpolarizing K(+) current.
      Repolarization after a test depolarization consistently evoked a transient inward
      'tail current' (ITail) that flowed via a second population of ion channels with
      poor (~3-fold) K(+) versus Na(+) selectivity. The activity of these channels was
      increased by quinidine, 4-AP and progesterone. Vm in human sperm is therefore
      dependent upon a hyperpolarizing K(+) current that flows via channels that most
      closely resemble those encoded by Slo3. Although 0.5 uM progesterone had no
      effect upon these channels, this hormone did activate the pharmacologically
      distinct channels that mediate ITail. In conclusion, this study reveals three
      functionally and pharmacologically distinct cation channels: Ik, ITail, ICatSper.

PMID- 24442344
TI  - Degradation of estrogen receptor alpha in activated blastocysts is associated
      with implantation in the delayed implantation mouse model.
AB  - Implantation of a blastocyst into a receptive uterus involves a series of highly
      coordinated cellular and molecular events directed by ovarian estrogen and
      progesterone. In particular, estrogen is essential for on-time uterine
      receptivity and blastocyst activation in mice. Although estrogen receptor alpha
      (ERalpha) is expressed in blastocysts, its targeted disruption leaves embryonic
      development and implantation unaffected. Therefore, the role of ERalpha in
      implanting blastocysts remains unclear. Using a delayed implantation model in
      mice, we showed increased expression of ERalpha in implantation-induced
      (activated) blastocysts; however, this ERalpha expression in activated
      blastocysts decreased within 6-h culture. In contrast, breast cancer 1 (Brca1)
      was maintained in the blastocysts during the culture. The treatment of activated
      blastocysts with the proteasome inhibitor MG132 demonstrated that proteolysis is
      associated with down-regulation of ERalpha expression in activated blastocysts.
      Embryo transfer of MG132-treated activated blastocysts into recipient mice on the
      morning of Day 4 of pseudopregnancy (Day 1 = vaginal plug) showed a decreased
      implantation rate, whereas combined treatment with MG132 and the ER antagonist,
      ICI 182,780, resulted in recovery of the rate of implantation. This study has
      revealed that down-regulation of ERalpha in activated blastocyst is associated
      with completion of blastocyst implantation after embryo transfer on the morning
      of Day 4 of pseudopregnancy. Our results also suggest that selective protein
      turnover, such as that of ERalpha, occurs in activated blastocysts, while
      expression of other proteins, including Brca1, is maintained at the same stage. 

PMID- 24442345
TI  - Activation of Janus kinase/signal transducers and activators of transcription
      pathway involved in megakaryocyte proliferation induced by vanadium resembles
      some aspects of essential thrombocythemia.
AB  - Vanadium (V) is an air pollutant released into the atmosphere by burning fossil
      fuels. Also, it has been recently evaluated for their carcinogenic potential to
      establish permissible limits of exposure at workplaces. We previously reported an
      increase in the number and size of platelets and their precursor cells and
      megakaryocytes in bone marrow and spleen. The aim of this study was to identify
      the involvement of Janus kinase/signal transducers and activators of
      transcription (JAK/STAT) pathway and thrombopoietin (TPO) receptor, and
      myeloproliferative leukemia virus oncogene (Mpl), in megakaryocyte proliferation
      induced by this compound. Mice were exposed twice a week to vanadium pentoxide
      inhalation (0.02 M) and were killed at 4th, 6th, and 8th week of exposure.
      Phosphorylated JAK2 (JAK2 ph), STAT3 (STAT3 ph), STAT5, and Mpl were identified
      in mice spleen megakaryocytes by cytofluorometry and immunohistochemistry. An
      increase in JAK2 ph and STAT3 ph, but a decrease in Mpl at 8-week exposure was
      identified in our findings. Taking together, we propose that the morphological
      findings, JAK/STAT activation, and decreased Mpl receptor induced by V leads to a
      condition comparable to essential thrombocythemia, so the effect on
      megakaryocytes caused by different mechanisms is similar. We also suggest that
      the decrease in Mpl is a negative feedback mechanism after the JAK/STAT
      activation. Since megakaryocytes are platelet precursors, their alteration
      affects platelet morphology and function, which might have implications in
      hemostasis as demonstrated previously, so it is important to continue evaluating
      the effects of toxics and pollutants on megakaryocytes and platelets. 

PMID- 24442346
TI  - The application of FLUENT in simulating outcomes from chlorine leakage accidents
      in a typical chemical factory.
AB  - For improvements in market competitiveness, old brand chemical enterprises did
      some expansion and reconstruction on the base of original equipment. Because it
      is the reconstruction on the basis of the existing production equipment, it is
      bound to raise problems of reutilization existing in pipelines and equipment. A
      simplified typical chemical factory was established referring the actual workshop
      layout. Further, trustable accident scenarios were conducted to reveal the
      diffusion process. In a larger leakage rate, the chlorine leak-affected area in
      the downwind became larger a bit, also in a relatively shorter time, lethal scope
      will become larger quickly, resulting in more threats to the lives and properties
      in the vicinity of the factories. Further, it is not possible that the heavier
      than-air effect of the chlorine will inevitably result in a higher concentration
      for a lower surface than that of higher surface. Actually at a certain height, a
      relatively higher monitoring surface has a larger diffusion range and a larger
      concentration than a relatively lower surface. It can be inferred that within a
      certain height, chlorine diffusion rate closer to the ground would be slower due
      to existence of turbulence or the relative resistance on the ground. 

PMID- 24442347
TI  - Comparison between the effects of quercetin on seizure threshold in acute and
      chronic seizure models.
AB  - Flavonoids are important constituents of food and beverages, and several studies
      have shown that they have neuroactive properties. Many of these compounds are
      ligands for gamma-aminobutyric acid type A receptors in the central nervous
      system. This study aimed to investigate the anticonvulsant effects of quercetin
      (3,3',4',5,7-pentahydroxyflavone), which is a flavonoid found in plants, in rats
      treated with pentylenetetrazole in acute and chronic seizure models. Single
      intraperitoneal administration of quercetin did not show anticonvulsive effects
      against acute seizure. Similarly, multiple oral pretreatment with quercetin did
      not have protective effects against acute seizure. However, multiple
      intraperitoneal administration of quercetin (25 and 50 mg/kg) significantly
      increased time to death compared with the control (p < 0.001). However, quercetin
      pretreatment had no significant effects on the pattern of convulsion development
      during all periods of kindling. But on the test day, quercetin (100 mg/kg) could
      significantly increase generalized tonic-clonic seizure onset (GTCS) and decrease
      GTCS duration compared with the control (p < 0.01, p < 0.05). We conclude that
      quercetin has a narrow therapeutic dose range for anticonvulsant activities in
      vivo, and it has different effects on the seizure threshold. The different
      effects of quercetin on seizure threshold may occur through several mechanisms. 

PMID- 24442348
TI  - Collimator performance evaluation for In-111 SPECT using a detection/localization
      task.
AB  - In SPECT, the collimator is a crucial element in controlling image quality. We
      take a task performance approach to collimator performance evaluation in which an
      ideal observer is applied to the raw camera data without regard to the subsequent
      reconstruction stage. The clinical context of our collimator study is one of
      searching for and detecting neuroendocrine tumor metastases in the liver as seen
      in In-111 Octreotide SPECT. Our task involves detection and localization of a
      signal and thus differs from the conventionally used detection-only task. The
      scalar task performance metric is ALROC, the area under the localization receiver
      operating characteristic curve. Since In-111 emits photons at both 171 and 245
      keV, the higher energy emissions can contribute significant septal scatter and
      penetration. Our collimator evaluations address a question previously considered
      by Mahler et al (2012 IEEE Trans. Nucl. Sci. 59 47-53) who used a different
      methodology: does allowing a limited amount of septal scatter and penetration
      yield improved task performance? We used simulation methods to evaluate five
      parallel-hole collimators. The collimators had roughly equal geometric
      sensitivity and resolution but a range of contributions from septal effects
      leading to variations in total sensitivity and resolution. We found that the best
      performance was obtained with a collimator that allowed a moderate amount of
      septal scatter and penetration.

PMID- 24442350
TI  - [Investigations on the oil content and saturation value of the oil of flax
      mutants and their correlation with some other plant characters].
AB  - An analysis of the oil content and the refractive index (as a measure of the
      saturation value of the oil) was carried out during 1961-1964 in a collection of
      about 700 mutants, derived by X-irradiation from the two stocks no. 6 and no.
      36.The average refractive index of the oil was highest under the cool and rainy
      conditions of 1961, lowest in the warm and dry year 1963. The maximum differences
      in the mean refractive index of the collections between 1961 and 1963 amount to
      an iodine number of 6 (mutants of stock no. 6) or 5 (mutants of stock no. 36)
      resp.The variability of both characters mentioned was significantly increased in
      the two mutant stocks. The average oil content showed, on the other hand, a
      decrease of about 1%. The degree of unsaturation of the oil is higher in the
      mutants derived from no. 6, and lower in the mutants derived from no. 36 when
      compared with the untreated material. In the present investigation no (no. 36) or
      negative correlation (no. 6) was found for the characters of oil content and
      refractive index.Subgrouping of such characters as plant height, seed coat color,
      flower color, etc. lead to more or less considerable differences in oil content
      and refractive index. It may be pointed out that mutants with yellow seed coat
      color are always characterized by a high oil content and a high refractive index.

PMID- 24442349
TI  - Techniques for the quantitative study of mutation in plant viruses.
AB  - Hardly any other virus is chemically and ultramicroscopically as well known as
      TMV. It is not possible to perform genetic recombinations with this object. The
      phenomenon of mutation is, however, known and an analysis of the dosis-effect
      relationship was possible by using the characters "chlorotic" versus "necrotic"
      primary symptoms. Taking into account the phenomenon of interference (mutual
      exclusion), i.e., comparing the induced mutation frequency with that of a control
      virus sample diluted to the same level of infectivity, on can perform
      quantitative analyses. In this way the first chemical mutagensis in the test tube
      was demonstrated 10 years ago with nitrous acid as mutagenic agent. The criticism
      raised byBAWDEN to the first publication ofMUNDRY andGIERER was already
      inappropriate at that time. In the meantime it has been demonstrated byWITTMANN
      LIEBOLD andWITTMANN through analysis of amino acid exchanges in spontaneous
      mutants and in those isolated after incubation with HNO2 that the "difference"
      between spontaneous and induced mutants demanded byBAWDEN, which cannot be
      postulated for symptoms in plants, lies, as expected, in amino acid exchanges of
      the protein coat. 

PMID- 24442351
TI  - Effects of chronic irradiation upon a self-incompatible clone ofLycopersicum
      peruvianum.
AB  - Flovering plants from a self-incompatible clone ofLycopersicum peruvianum were
      exposed during 90 days to different dose-rates of gamma-rays ranging from 2 to 17
      rad perhour. Irradiation was continuous, except for a daily interruption of 7
      hours.Whereas irradiation at dose-rates higher than 7.50 rad per hour seriously
      inhibited bud formation and floral development, chronic exposure at dose-rates
      ranging from 3 to 7 rad/hour increased the number of seeds per plant. This
      stimulation is not due to a higher number of seeds per fruit but to a very
      significant rise in the number of fruits per plant. As irradiation treatment did
      not significantly increase the number of flowers per plant and did not appear to
      stimulate pollen tube germination in the styles, it is concluded that the
      recorded increase in fruit-setting essentially resulted from a radio-induced
      inhibition of the processes which control floral abscission in the absence of
      cross-pollination.Three plants with reduced self-incompatibility and one
      completely parthenocarpic individual were observed in theM 2 progeny but no
      evidence was obtained that irradiation could induce a permanent type of self
      compatibility inL. peruvianum. 

PMID- 24442352
TI  - [Endopolyploidy and yield in diploid and tetraploid sugar beets II].
AB  - In diploid sugar beet the mesophyll cell sizes, arising from
      endotetraploidization, are well adapted to optimal yield requirements. In
      tetraploid sugar beet, however, the mesophyll cells of most plants become
      endooctoploid and hence too large. Trying to eliminate all endopolyploidy from
      tetraploids is not advisable, but some reduction of its extent seems
      advantageous. 

PMID- 24442353
TI  - Some data on the polygenic control of two quantitative traits in a vegetatively
      propagated flower plant, the carnation.
AB  - In two populations of selfed commercial varieties 4800 and 5774 ofDianthus
      cariophyllus as well as in the parents of 5774 two quantitative traits were
      examined: petal number and durability of blossoms after cutting. Both populations
      showed an increase in the number of petals, No. 4800 also in its durability. The
      estimated hereditary component was high for petals (0.47 and 0.35), lower but
      significant for lasting quality. The importance of an investigation on the
      selection for quantitative traits in cut flowers is discussed. 

PMID- 24442354
TI  - [Estimating variance components in a fixed model of variance analysis].
AB  - The partition of a variance into components in experiments with fixed effects,
      i.e. experiments with varieties, treatment etc., is meaningful only if
      "components" are defined as additive parts of a whole. This also demands that the
      sum of the components of variance be equal to the total variance. Such additivity
      of the components of variance is achieved by appropriate definitions of the
      components of variance. Unbiassed estimates of the additively defined components
      of variance are obtained by a simple correction which eliminates the influence of
      degrees of freedom on the calculation of mean squares. This correction is not
      needed for the estimation of variances of random effects.The expected values of
      mean squares for the partition of variance and formulas for unbiassed estimates
      of additively defined components of variance are demonstrated in an experiment
      with two fixed effects and one random effect. 

PMID- 24442355
TI  - Growth of the laboratory mouse.
AB  - Body weights and tail lengths were observed every 3 days from birth to 60 days of
      age and every 6 days from 60 to 96 days in four lines of mice: C57BL/6J, an
      inbred; J, a synthetic outbred; GR, Goodale large body size line; and FR,
      Falconer large body size line. Mean 96-day body weights for lines C57BL, J, GR
      and FR were 25.4, 29.7, 48.8 and 49.1 gm for males, and 19.9, 23.8, 38.5 and 38.2
      gm for females, respectively. Lines GR and FR gave identical body weights at all
      ages studied. Both of these lines had previously plateaued in response to
      selection for large body size. The variability in body weight was smallest for
      lines C57BL and J, intermediate for FR and highest for GR. The pattern of
      variance over time was very similar in all lines and both sexes, showing a
      minimum at birth and a maximum at age of inflection. Growth in tail length of the
      four lines showed similar between line differences except that length in GR was
      greater than in FR. Age at vaginal opening in females coincided closely with age
      of inflection in body weight growth. Age at point of inflection did not differ
      between lines but appeared to occur somewhat earlier in females than in males. 

PMID- 24442356
TI  - [On the problem of change in the proportions of amylose/amylopectin in potato
      starch through breeding].
AB  - 85 wild and cultivated potato species of 6120 genotypes from 2818 different
      sources were investigated in order to find out whether breeding of potato
      varieties with changed proportions of amylose: amylopectin were possible. The
      main purpose was to raise the amylose portion of the starch.While the best
      varieties have proportions of about 28% amylose to 72% amylopectin, clones with
      30-33% amylose could be found among cultivated potatoes.A positive correlation
      between amylose content of the parents and their progeny after selfing, crosses
      between sibs, and of the mentioned amylose-rich clones with 2 x or 4 xS.
      tuberosum could be ascertained.A weak negative correlation between the amount of
      starch content and amylose conten was found which, however, need not be a
      deterrent to successful breeding.Preliminary results from hybrid progeny indicate
      the possibility of breeding varieties with increased amylose content. The
      necessary breeding steps are given. 

PMID- 24442357
TI  - [Contributions to the problem of plastid change : V. Another(35)S-induced nuclear
      gene mutant effecting plastid changes].
AB  - Seeds ofEpilobium hirsutum were treated with 0.5 mC(35)S isotope. One treated
      plant gave rise to variegated plants when selfed. Crosses revealed that this was
      caused by a recessive gene mp2 which induces plastid mutations.That the observed
      variegation was due to mutations of the plastids could be derived from the
      evidence of the characteristic patterns of the leaves and from the occurrence of
      actual mixed cells. Maternal inheritance of the mutated plastids could not be
      demonstrated as the mp2 gene induces most of the plastid mutations too late in
      the development of the leaves to exert an effect on the shoots and cell lines
      giving rise to egg cells. 

PMID- 24442358
TI  - [The effectiveness of selection of alfalfa from a drilled stock and in early
      stage].
AB  - Positive selection of alfalfa shoots from a drilled stock showed a negative
      effect in the progeny tested under drilling conditions. The selection of largest
      plants in an early stage showed the same result. It could be proven in both cases
      that material from self-fertilization was preferred. This results in inbreeding
      depression. Self-fertilization caused a decrease in the number of seeds per pod.
      This, in turn, allowed some seeds to become larger and young plants more robust
      than with natural cross-pollination. 

PMID- 24442359
TI  - Environmental investigations and molecular typing of Aspergillus in a Chinese
      hospital.
AB  - Invasive fungal infections due to Aspergillus species have become a major cause
      of morbidity and mortality among immunocompromised patients. In order to
      determine the possible relationship between environmental contamination by
      Aspergillus and the occurrence of invasive aspergillosis, a 1-year prospective
      study was carried out in a tertiary hospital in China. Air, surface, and tap
      water sampling was performed twice monthly at the bone marrow transplant (BMT)
      department, intensive care unit (ICU), neurosurgery intensive care unit (NICU),
      and outdoors. Nose, pharynx, and sputum samples were collected from high-risk
      patients. Isolates of Aspergillus from the environment and patients were
      genotyped by random amplification of polymorphic DNA (RAPD) assay to investigate
      the origin of infection. Mean total Aspergillus count was 7.73, 8.94, 13.19, and
      17.32 cfu/m(3) in the BMT department, ICU, NICU, and outdoors, respectively. RAPD
      analysis by R108 primer demonstrated that strains isolated from patients in NICU
      were identical to the environmental strain. Strains isolated from patients in ICU
      differed from the environmental strain. Aspergillus contamination was found in
      the BTM department, NICU, and ICU. Clinical and environmental strains from NICU
      had identical genotypes. These findings suggest that Aspergillus is found in the
      hospital environment including the air, surface, and tap water. The genotypes of
      Aspergillus were identical from patients and the environment, suggesting that
      clinical infection may originate from the hospital environment.

PMID- 24442361
TI  - Physiological comparisons of two soybean cultivars differing in canopy
      photosynthesis. I. Variation in vertical (14)CO 2 labelling and dry weight
      partitioning.
AB  - Differences in canopy apparent photosynthesis (CAP) among soybean [Glycine max
      (L.) Merr.] genotypes have been shown to be correlated to seed yields. Since the
      physiological basis for such differences in CAP is unknown, two cultivars known
      to differ in CAP, 'Tracy' and 'Davis', were studied during the 1978-1980 growing
      seasons. The CAP and dry weights of component plant parts were determined. In
      1978 and 1979, (14)CO2 uptake by vertical leaf strata was determined and specific
      leaf weight (SLW) and leaf area index (LAI) were determined for corresponding
      strata in 1979 and 1980. Measurements were taken on several dates during
      reproductive growth. With the exception of CAP, all measurements ((14)C uptake,
      dry weights) were made in layers within the canopy. CAP on some dates were
      significantly higher in Tracy than in Davis and integrated CAP values from a
      certain growth period, labeled as R5 to R7, averaged 16 percent higher in Tracy
      for the three years studied. No differences in the relative recovery of (14)C
      from different layers of leaves in the canopy were found. This indicates that
      variations in canopy structure or leaf orientation did not play a major role in
      the CAP differences between cultivars. The differences seem related to variations
      in leaf dry weights. Overall, Tracy exhibited 13.5, 19.2, and 13.2 percent
      greater leaf dry weights than Davis during 1978, 1979, and 1980, respectively.
      These differences in leaf dry weight seem largely due to a differences in the
      SLW. Data from these experiments indicate that differences in soybean CAP values
      were associated with differences in SLW. 

PMID- 24442362
TI  - Physiological comparisons of two soybean cultivars differing in canopy
      photosynthesis. II. Variation in specific leaf weight, nitrogen, and protein
      components.
AB  - Cultivar differences in canopy apparent photosynthesis (CAP) have been observed
      in soybean (Glycine max (L.) Merr.) but little is known about the physiological
      mechanisms which are responsible for such differences. This study was initiated
      to determine if variation in ribulose 1,5-bisphosphate carboxylase (RuBPCase) and
      soluble protein exists among cultivars which differ in CAP during reproductive
      growth. In addition, the relationship between specific leaf weight (SLW) and leaf
      protein was examined. Two Maturity Group VI cultivars, 'Tracy' (high CAP) and
      'Davis' (low CAP), were grown in the field during 1979, 1980, and 1981 and in a
      greenhouse experiment. Leaves located at two canopy positions (topmost, fully
      expanded leaf and eighth node from the top) in 1979 and three canopy positions
      (those mentioned, plus the fourth node from the top) in 1980 and 1981 were
      sampled. Leaves at the two upper canopy positions exhibited greater SLW, RuBPCase
      m(-2), and soluble protein m(-2) than found at the eighth node down.
      Photosynthetic capacity of leaves at inner canopy regions was therefore affected
      by both light penetration into the canopy and leaf protein status. Over the three
      year period, the SLW was 23 percent and the soluble protein m(-2) leaf 21 percent
      greater in Tracy than in Davis. Although the trend in RuBPCase m(-2) leaf was not
      significant, it was consistently greater in Tracy in the field and greenhouse. No
      cultivar differences were observed when the proteins were expressed on a unit of
      leaf dry weight. The quantity of RuBPCase per unit leaf area was positively
      correlated with SLW with significant partial correlation coefficients of 0.62,
      0.67, 0.35, and 0.82 for 1979, 1980, 1981, and the greenhouse study,
      respectively. Since these cultivars have similar leaf area indices during
      September, the greater SLW of Tracy is translated into more photosynthetic
      proteins per unit ground area and higher CAP rate. 

PMID- 24442360
TI  - Common variants in genes of the postsynaptic FMRP signalling pathway are risk
      factors for autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are heterogeneous disorders with a high
      heritability and complex genetic architecture. Due to the central role of the
      fragile X mental retardation gene 1 protein (FMRP) pathway in ASD we investigated
      common functional variants of ASD risk genes regulating FMRP. We genotyped ten
      SNPs in two German patient sets (N = 192 and N = 254 families, respectively) and
      report association for rs7170637 (CYFIP1; set 1 and combined sets), rs6923492
      (GRM1; combined sets), and rs25925 (CAMK4; combined sets). An additional risk
      score based on variants with an odds ratio (OR) >1.25 in set 1 and weighted by
      their respective log transmitted/untransmitted ratio revealed a significant
      effect (OR 1.30, 95 % CI 1.11-1.53; P = 0.0013) in the combined German sample. A
      subsequent meta-analysis including the two German samples, the "Strict/European"
      ASD subsample of the Autism Genome Project (1,466 families) and a French
      case/control (541/366) cohort showed again association of rs7170637-A (OR 0.85,
      95 % CI 0.75-0.96; P = 0.007) and rs25925-G (OR 1.31, 95 % CI 1.04-1.64; P =
      0.021) with ASD. Functional analyses revealed that these minor alleles predicted
      to alter splicing factor binding sites significantly increase levels of an
      alternative mRNA isoform of the respective gene while keeping the overall
      expression of the gene constant. These findings underpin the role of ASD
      candidate genes in postsynaptic FMRP regulation suggesting that an imbalance of
      specific isoforms of CYFIP1, an FMRP interaction partner, and CAMK4, a
      transcriptional regulator of the FMRP gene, modulates ASD risk. Both gene
      products are related to neuronal regulation of synaptic plasticity, a
      pathomechanism underlying ASD and may thus present future targets for
      pharmacological therapies in ASD.

PMID- 24442363
TI  - Photosynthetic and leaf morphological characteristics in Leucaena leucocephala as
      affected by growth under different neutral shade levels.
AB  - Morphological and physiological measurements on individual leaves of Leucaena
      leucocephala seedlings were used to study acclimation to neutral shading. The
      light-saturated photosynthetic rate (Pn max) ranged from 19.6 to 6.5 MUmol CO2 m(
      2) s(-1) as photosynthetic photon flux density (PPFD) during growth decreased
      from 27 to 1.6 mol m(-2) s(-1). Stomatal density varied from 144 mm(-2) in plants
      grown in high PPFD to 84 mm(-2) in plants grown in low PPFD. Average maximal
      stomatal conductance for H2O was 1.1 in plants grown in high PPFD and 0.3 for
      plants grown in low PPFD. Plants grown in low PPFD had a greater total
      chlorophyll content than plants grown in high PPFD (7.2 vs 2.9 mg g(-1) on a unit
      fresh weight basis, and 4.3 vs 3.7 mg dm(-2) on a unit leaf area basis). Leaf
      area was largest when plants were grown under the intermediate PPFDs. Leaf
      density thickness was largest when plants were grown under the largest PPFDs. It
      is concluded that L. leucocephala shows extensive ability to acclimate to neutral
      shade, and could be considered a facultative shade plant. 

PMID- 24442364
TI  - Photosynthetic characteristics and chloroplast ultrastructure of C3 and C 4 tree
      species grown in high- and low-light environments.
AB  - Plants of the C4 tree species, Euphorbia forbesii, Sherff and the C3 tree
      species, Claoxylon sandwicense Muell-Arg., were grown in a full sun and a shade
      environment designed to simulate the understory of their native Hawiian forest
      habitat. When grown under shade conditions, both species exhibited a
      photosynthetic light response typical of shade plants with low light compensation
      points and low dark respiration rates. E. forbesii, however, exhibited greater
      acclimation of light saturated photosynthetic rates and no evidence of
      photoinhibition in high light. In contrast, quantum yields for CO2 uptake and
      chlorophyll contents were reduced in the high-light as compared to the low-light
      grown C. sandwicense plants. Both species exhibited similar changes in the
      intercellular CO2 response curves and chloroplast whole-chain electron transport
      capacities, suggesting that the underlying mechanisms of light acclimation are
      similar. Chloroplasts of E. forbesii exhibited large changes in ultrastructure,
      with much greater thylakoid membrane development in low than high light. In
      contrast, C. sandwicense exhibited different starch contents, but otherwise
      similar membrane development in high and low light. The results show that E.
      forbesii possesses a very flexible photosynthetic apparatus which may account for
      its ability to survive in the understory of shaded forests. 

PMID- 24442365
TI  - Differential response of stomata to air humidity in the parasitic mistletoe
      (Phthirusa pyrifolia) and its host, mandarin orange (Citrus resitulata).
AB  - Measurements of CO2 and H2O exchange rate and the calculated leaf conductance of
      attached leaves were conducted over a range of leaf-to-air vapour pressure
      difference (VPD) (1.5 to 5.5 kPa) to compare the response of the parasitic
      mistletoe, Phthirusa pyrifolia, with that of its host, the mandarin orange,
      Citrus reticulata. Seedlings of the host infected with the parasite were grown in
      well-watered and adequately fertilized large pots outdoors at the CIAT
      headquarters, Palmira, Colombia, South America. Observations of leaf anatomy of
      the parasite and nutrient analysis of young tissues of both the parasite and host
      were made. The photosynthetic rate of the host decreased linearly with increased
      VPD, whereas the parasite showed a constant rate. This trend coincided with
      similar responses in leaf conductance. Due to the insensitivity of the parasite
      stomata, the transpiration rate increased linearly with VPD as compared with an
      initial increase and then a decrease in the host transpiration rate. The higher
      photosynthetic rate and the closure of stomata of the host resulted in high water
      use efficiency as compared with that of the parasite. The parasite accumulated in
      its leaves more N, P, K and less Ca and Mg than the host. The significance of the
      host-parasite differential response to air humidity is discussed in relation to
      mechanism underlying stomatal sensitivity and in the context of host-parasite
      association. 

PMID- 24442366
TI  - A system for measuring leaf gas exchange based on regulating vapour pressure
      difference.
AB  - A system for measurement of leaf gas exchange while regulating leaf to air vapour
      pressure difference has been developed; it comprises an assimilation chamber,
      leaf temperature controller, mass flow controller, dew point controller and
      personal computer. A relative humidity sensor and air and leaf temperature
      sensors, which are all used for regulating the vapour pressure difference, are
      mounted into the chamber. During the experiments, the computer continuously
      monitored the photosynthetic parameters and measurement conditions, so that
      accurate and intenstive measurements could be made.When measuring the light
      response curve of CO2 assimilation for single leaves, in order to regulate the
      vapour pressure difference, the leaf temperature and relative humidity in the
      chamber were separately and simultaneously controlled by changing the air
      temperature around the leaf and varying the air flow rate through the chamber,
      respectively. When the vapour pressure difference was regulated, net CO2
      assimilation, transpiration and leaf conductance for leaves of rice plant
      increased at high quantum flux density as compared with those values obtained
      when it was not regulated.When measuring the temperature-response curve of CO2
      assimilation, the regulation of vapour pressure difference was manipulated by the
      feed-forward control of the dew point temperature in the inlet air stream. As the
      vapour pressure difference was regulated at 12 mbar, the maximum rate of and the
      optimum temperature for CO2 assimilation in rice leaves increased 5 MUmolCO2 m(
      2) s(-1) and 5 degrees C, respectively, as compared with those values obtained
      when the vapour pressure difference took its own course. This was reasoned to be
      due to the increase in leaf conductance and the decrease in transpiration rate.
      In addition, these results confirmed that stomatal conductance essentially
      increases with increasing leaf temperature under constant vapour pressure
      difference conditions, in other words, when the influence of the vapour pressure
      difference is removed.This system may be used successfully to measure inter- and
      intra-specific differences and characteristics of leaf gas exchange in plants
      with a high degree of accuracy. 

PMID- 24442367
TI  - A study of factors which regulate the membrane appression of lettuce thylakoids
      in relation to irradiance.
AB  - Factors that may influence the extent of thylakoid membrane appression have been
      examined using lettuce (Lactuca sativa cv. Celtuce) grown under different
      irradiances. Electron microscopy and salt-induced chlorophyll fluorescence
      suggest that the percentage of membrane appression is increased in plants grown
      in low light (20 Wm(-2)) compared with those grown in high light (150 Wm(-2)). In
      high light plants surface charge, as measured by 9-aminoacridine, was found to be
      twice that measured in low light plants. There was a similar difference in ATPase
      activity of CF1 and in light saturated photophosphorylation. The chlorophyll
      content of LHC-2 as a proportion of the total chlorophyll was greatest in
      thylakoids of low light plants. Measurement of non-cyclic photophosphorylation
      rates suggested that membrane appression has a stimulatory role in the
      photophosphorylation process. The importance of these inter-related factors for
      the mechanism of thylakoid appression is discussed. 

PMID- 24442368
TI  - Rituximab for treating CD20+ prostate cancer with generalized lymphadenopathy: a
      case report and review of the literature.
AB  - A role for CD20 antibodies in treating prostate cancer has not yet been
      established. We report a case of advanced prostate cancer presenting with
      generalized lymphadenopathy that expressed CCR7 and CD20. CCR7 expression in
      prostate cancer has been previously reported only once; the expression of CD20
      has not been reported before. Rituximab therapy was initiated in this case and
      resulted in a significant biochemical response. This unique metastatic and
      biochemical pattern may signify a distinct subtype of prostate cancer that may be
      amenable to treatment with anti-CD20 antibodies.

PMID- 24442369
TI  - Panel perception of facial appearance of cleft patients generated by use of a
      morphing technique.
AB  - OBJECTIVE: Perception of the facial appearance of cleft patients has, until now,
      been evaluated on the basis of photographs of the patients. Research based on
      photographs generated by use of a morphing technique has not yet been reported.
      The purpose of this study was to investigate female and male raters' panel
      perception with regard to the following: (1) patient age, (2) attractiveness, (3)
      gender appearance, and (4) likeability of faces of cleft patients generated by
      the use of a morphing technique. SETTING: The study was conducted at the
      Department of Oral, Craniomaxillofacial and Facial Plastic Surgery, University
      Hospital of Leipzig, Germany. PATIENTS, PARTICIPANTS: We used photographs of 32
      adult German nonsyndromic cleft patients, mean age 18.9 +/- 1.3 years, and
      surveyed 93 students, mean age 25.3 +/- 3.2 years, by use of a standardized
      questionnaire. RESULTS: All respondents rated the mean age of cleft patients
      equally in unmorphed and morphed pictures. For all respondents, attractiveness of
      morphed patient pictures was rated significantly higher than for unmorphed
      pictures (mean 4.8 +/- 1.0 vs. 6.4 +/- 2.4; p < 0.001), although significance was
      reached only if morphed pictures of eight patients were rated. Female respondents
      rated attractiveness significantly higher than did males, especially for pictures
      of female patients. CONCLUSION: Facial morphing of patient pictures is a suitable
      method for creation of standard cleft faces. Despite the modification of the
      pictures, the faces generated remain human and assessable by panel members.
      Perception of faces of cleft patients' depended on raters' gender.

PMID- 24442370
TI  - Flow cytometry analysis of cell population dynamics and cell cycle during HIV-1
      envelope-mediated formation of syncytia in vitro.
AB  - Cell fusion occurs in physiological and pathological conditions and plays a role
      in regulation of cell fate. The analysis of cell population dynamics and cell
      cycle in cell-cell fusion experiments is necessary to determine changes in the
      quantitative equilibrium of cell populations and to identify potential bystander
      effects. Here, using cocultures of Jurkat HIV-1 envelope expressing cells and
      CD4(+) cells as a model system and flow cytometry for the analysis, the number,
      viability, and cell cycle status of the populations participating in fusion were
      determined. In 3-day cocultures, a sustained reduction of the number of CD4(+)
      cells was observed while they showed high viability and normal cell cycle
      progression; fusion, but not inhibition of proliferation or death, accounted for
      their decrease. In contrast, the number of Env(+) cells decreased in cocultures
      due to fusion, death, and an inherent arrest at G1. Most of syncytia formed in
      the first 6 h of coculture showed DNA synthesis activity, indicating that the
      efficient recruitment of proliferating cells contributed to amplify the removal
      of CD4(+) cells by syncytia formation. Late in cocultures, approximately 50% of
      syncytia were viable and a subpopulation still underwent DNA synthesis, even when
      the recruitment of additional cells was prevented by the addition of the fusion
      inhibitor T-20, indicating that a population of syncytia may progress into the
      cell cycle. These results show that the quantitative analysis of cellular
      outcomes of cell-cell fusion can be performed by flow cytometry. 

PMID- 24442371
TI  - Micronucleus assay in bovine lymphocytes after exposure to bisphenol A in vitro.
AB  - Bisphenol A (BPA) [2,2-bis-(4-hydroxyphenyl) propane] is an important industrial
      agent, made by combining acetone and phenol, that is used extensively as a
      monomer in the production of polycarbonate plastics and as a precursor of epoxy
      resins. Micronucleus assays have served as an index of cytogenetic damage in in
      vivo and in vitro studies. We studied the genotoxic and cytotoxic effects of BPA
      on bovine peripheral lymphocytes in vitro. Lymphocyte cultures from two donors
      were exposed to four different concentrations of BPA (1 * 10(-4), 1 * 10(-5), 1 *
      10(-6), and 1 * 10(-7) mol.L(-1)) for 48 h. The highest concentration of BPA (1 *
      10(-4) mol.L(-1)) resulted in a significant increase in the number of micronuclei
      in comparison with the negative control (67.50 +/- 2.121/1,000 binucleated cells
      versus 36.0 +/- 5.657/1,000 binucleated cells in the DMSO control, P = 0.018).
      BPA did not affect the nuclear division index at any treatment concentrations.
      The present results thus demonstrate a significant genotoxic effect by BPA on
      bovine peripheral lymphocytes in vitro, only at the highest concentration.

PMID- 24442372
TI  - Studies on the possible occurrence of actomyosin-like proteins in phloem.
AB  - Extracts of large quantities of petioles and of isolated vascular tissues of
      Heracleum mantegazzianum have been analysed for actomyosin-like contractile
      proteins. Concentrated preparations, subjected to a standard isolation and
      purification procedure for actomyosin, failed to demonstrate either
      superprecipitation or viscosity changes in response to the addition of ATP and
      divalent cations. In addition, ATPase activities in phloem and xylem extracts
      have been fractionated by gel electrophoresis and characterised with regard to
      their substrate specificity, pH optima and ion requirements. Phloem extracts
      provide two phosphatases: one is non-specific in its substrate requirements; the
      other is a nucleoside triphosphatase but is stimulated only by monovalent cations
      and is also present in xylem extracts. All the enzymes are strongly inhibited by
      divalent cations and do not possess any of the characteristics of ATPases
      associated with contractile systems. The results are discussed in relation to the
      postulated involvement of contractile proteins in the translocation of sugars in
      phloem. 

PMID- 24442373
TI  - [Precursors of chloroplast ribosomal RNA and their maturation in Chlorella].
AB  - In Chlorella pyrenoidosa, tritiated uridine is incorporated specifically into the
      RNA of the chloroplast. The 16 S and 23 S ribosomal RNA become labeled after at
      least 15 min. Short pulse labeling of 5 min results in peaks of radioactivity in
      the 17 S region and at the heavy side of the 23 S peak, as shown by
      polyacrylamide electrophoresis.During chase treatment with unlabeled uridine
      after the pulse labeling, a shift of radioactivity from the 17 S to the 16 S
      region is observed. At the same time, the radioactivity over the 23 S speak
      becomes symmetrical. In the 17 S region, there are at least two peaks which
      appear and disappear during chase treatment. From data of specific radioactivity
      a precursor-end product relation can be deduced.After blocking of the chloroplast
      translation with spectinomycin, the RNA in the 17 S region is accumulated. This
      product is not stringently the same as that from pulse labeling experiments,
      because it migrates slightly faster than 17 S RNA. Removal of the antibiotic
      results in a shift of the radioactivity to the 16 S region. At the same time, the
      previously blocked chloroplast ribosome synthesis is reinitiated.Attempts have
      been made to localize the precursor molecules of 17 S and 23 S within the cell.
      By means of differential centrifugation it has been shown that the precursor RNA
      components are located in ribosomal particles. No free precursor molecules are
      found in the ribosome-free supernatant. This is the case in normal as well as in
      spectinomycin-treated cells.The results are discussed in view of the possible
      role of chloroplast ribosomal particles as processing agents for the maturation
      of chloroplast ribosomal RNA. 

PMID- 24442374
TI  - The control of the production of lactate and ethanol by higher plants.
AB  - Factors controlling the production of ethanol and lactate have been examined
      using cell free extracts prepared from pea seeds (Pisum sativum var Alaska) and
      parsnip roots (Pastinaca sativa). The result suggest that under aerobic
      conditions pyruvate decarboxylase is inactive. With the onset of anaerobiosis
      glycolysis leads to an accumulation of lactate with a corresponding fall in pH.
      The fall in pH activates pyruvate decarboxylase and initiates competition between
      lactate dehydrogenase and pyruvate decarboxylase for pyruvate. The effect of
      pyruvate concentration on the partitioning has been analysed in terms of a
      modified Wegscheider rule and shows that the ratio lactate dehydrogenase
      activity/pyruvate decarboxylase activity bears an inverse relationship to the
      pyruvate concentration. The decrease in ratio which occurs when the pyruvate
      concentration rises is enhanced by the co-operativity which is exhibited by
      pyruvate decarboxylase. The pH optimum of lactate dehydrogenase is alkaline
      whilst the pH optimum of pyruvic decarboxylase is acid, thus the two enzymes
      function as a pH-stat. The possibility of excessive production of lactic acid is
      further controlled by the response of lactate dehydrogenase to ATP; the enzyme is
      inhibited by ATP and the inhibition increases as the pH decreases. It is
      suggested that this mechanism functions to protect the plant from excess
      production of acid. 

PMID- 24442375
TI  - Basipetally polarised transport of [(3)H]gibberellin A 1 and [ (14)C]gibberellin
      A 3, and acropetal polarity of [ (14)C]indole-3-acetic acid transport, in stelar
      tissues of Phaseolus coccineus roots.
AB  - Movement of both [(3)H]GA1 and [(14)C]GA3 through root segments from P. coccineus
      seedlings was basipetally polarised. The basipetal/acropetal ratio of
      radioactivity from [(3)H]GA1 in agar receiver blocks was 9.2 for apical,
      elongating segments, and 4.0 for more basal, non-elongating segments. Polarity of
      gibberellin transport was restricted to the stele, and absent from cortical
      tissues. Transport of [(14)C]IAA through root segments to agar receivers was
      preferentially acropetal, particularly so in the stele. Despite the existence of
      basipetal polarity of gibberellin transport in the root, [(3)H]GA1 injected into
      cotyledons moved into and acropetally along the seedling root. 

PMID- 24442376
TI  - Distribution of acid ribonuclease and other enzymes in stratified Acetabularia.
AB  - A method for producing stratified and viable subcells, consisting of segments of
      the stalk, has been worked out in Acetabularia mediterranea (LmX). Centrifugation
      at low speed results in the formation of a cytoplasmic moiety at the centrifugal
      pole which contains ca. 90% of the aldolase activity that is localized in the
      chloroplasts and in the cytosol. The vacuolar moiety, which occupies 80-92% of
      the cell volume, stains with neutral red, i.e. is viable. It contains ca. 76% of
      the total RNase and 72% of the total phosphotase activity. It is concluded that a
      large proportion of these hydrolase activities is present in the vacuole. 

PMID- 24442377
TI  - Alkaline beta-fructofuranosidases of tuberous roots: Possible physiological
      function.
AB  - Alkaline invertase of roots of carrot (Daucus carota L.) did not hydrolyze
      raffinose while the acid invertase from the same tissue showed with this sugar
      ca. 60% of the activity found with sucrose. The activity of the two invertases
      was inhibited by fructose to a different extent, the K i value being ca. 4*10(-2)
      M and 3*10(-1)M, respectively, for the alkaline and the acid invertases from the
      roots of both carrot and turnip (Brassica rapa L.). It is proposed that fructose
      inhibition of acid invertase is of no physiological significance but that, in
      contrast, hexoses might regulate the activity of alkaline invertase.Comparing
      several species and cultivars, it was found that the content of reducing sugars
      and the activity of alkaline invertase of mature tuberous roots showed a positive
      correlation. This indicates that alkaline invertase may participate in the
      regulation of the hexose level of the cell, as was previously suggested for sugar
      cane. A scheme is presented which proposes a way of participation of alkaline
      invertase in such a regulation, assuming that this enzyme is located in the
      cytoplasm and acid invertase is membrane-bound and mainly located at the cell
      surface. 

PMID- 24442378
TI  - Particle-bound phytochrome: Spectral properties of bound and unbound fractions.
AB  - In-vitro irradiation of extracts of maize (Zea mays L.) coleoptiles with red
      light enhances phytochrome pelletability as was previously reported for Cucurbita
      pepo L. In neither case is this the result of an irradiation-induced increase in
      the level of total pelletable protein. The transformation difference spectra of
      bound and unbound phytochrome fractions obtained after both in-vivo and in-vitro
      irradiations are not significantly different. The data, therefore, do not
      indicate that irradiation-enhanced pelletability either in vivo or in vitro
      results from phytochrome denaturation. Other non-photoreversible changes in the
      molecule external to the chromophore environment might however still account for
      the observed pelletability. 

PMID- 24442379
TI  - In-vitro binding of phytochrome to a particulate fraction: A function of light
      dose and steady-state P fr level.
AB  - The binding of phytochrome to a particulate fraction in extracts from hypocotyl
      hooks of etiolated Cucurbita pepo L. seedlings has been examined as a function of
      the light dose and P fr level established in vitro. As the steady-state level of
      P fr transiently established in the 500*g supernatant is increased, so the level
      of P r subsequently pelletable at 20 000*g increases up to a saturation level.
      Increasing both the time and irradiance parameters of the light dose while
      holding the steady-state P fr level constant, results similarly in increasing P r
      pelletability. This agrees with results obtained previously with in-vivo
      irradiations of maize coleoptiles. Thus, like the in-vivo response, phytochrome
      binding in vitro appears to be a function of the total number of molecules
      converted to the P fr form during the irradiation period. 

PMID- 24442380
TI  - Regulators of cell division in plant tissues : XXI. Distribution coefficients for
      cytokinins.
AB  - The distribution of six cytokinins [zeatin, zeatin riboside, 6-(4-hydroxy-3
      methylbutylamino)purine, 6-(3-methylbut-2-enylamino)purine and its riboside, and
      kinetin] between aqueous buffers (pH 3.0 and 7.0) and several organic solvents
      was assessed and partition coefficients calculated. Purification of cytokinins
      from plant extracts by solvent partition methods is discussed. 

PMID- 24442381
TI  - Preference on cash-choice task predicts externalizing outcomes in 17-year-olds.
AB  - Delay-discounting, the tendency to prefer a smaller-sooner reward to a larger
      later reward, has been associated with a range of externalizing behaviors.
      Laboratory delay-discounting tasks have emerged as a useful measure to index
      impulsivity and a proclivity towards externalizing pyschopathology. While many
      studies demonstrate the existence of a latent externalizing factor that is
      heritable, there have been few genetic studies of delay-discounting. Further, the
      increased vulnerability for risky behavior in adolescence makes adolescent
      samples an attractive target for future research, and expeditious, ecologically
      valid delay-discounting measures are helpful in this regard. The primary goal of
      this study was to help validate the utility of a "cash-choice" measure for use in
      a sample of older adolescents. We used a sample of 17-year-old twins (n = 791)
      from the Minnesota Twin Family Enrichment study. Individuals who chose the
      smaller-sooner reward were more likely to have used a range of addictive
      substances, engaged in sexual intercourse, and earned lower GPAs. Best fitting
      biometric models from univariate analyses supported the heritability of cash
      choice and externalizing, but bivariate modeling results indicated that the
      correlation between cash-choice and externalizing was determined largely by
      shared environmental influences, thus failing to support cash-choice as a
      possible endophenotype for externalizing in this age group. Our findings lend
      further support to the utility of cash-choice as a measure of individual
      differences in decision making and suggest that, by late adolescence, this task
      indexes shared environmental risk for externalizing behavior.

PMID- 24442382
TI  - Ramadan fasting ameliorates oxidative stress and improves glycemic control and
      lipid profile in diabetic patients.
AB  - PURPOSE: The effects of Ramadan fasting on public health are important. The
      present study characterized the metabolic effects of Ramadan fasting and
      evaluated its influence on oxidative stress in diabetic patients. METHODS: The
      current study was carried out in the city of Benha, Egypt, during the period from
      July 12, 2012 to October 4, 2012. This corresponds to 22 Shaban 1433 to 18 Dhul
      Al-Qi'dah 1433 in the Islamic Calendar. Two equal, sex- and age-matched groups (n
      = 40 each; age 55 +/- 5 years) of non-diabetic subjects (ND group) and diabetic
      patients (D group) were recruited for this study. Parameters of glycemic control,
      lipid profile, and oxidative stress were measured pre-, during and post-fasting.
      RESULTS: Ramadan fasting reduced fasting blood glucose (FBG) insignificantly by
      5.8% and significantly by 23.0% in the (ND) and (D) groups, respectively. Serum
      triglycerides (TG) and malondialdehyde (MDA) were lowered significantly by: TG
      (22.8, 22.1%), MDA (54.3, 46.6%), and total cholesterol (TC) and low-density
      lipoproteins (LDL) insignificantly by: TC: (4.7, 6.1%), LDL: (4.0, 5.1%), whereas
      high-density lipoproteins (HDL) were raised significantly by 6.7% and
      insignificantly by 2.2%, and blood glutathione (GSH) significantly by 52.6 and
      59.4%, in the (ND) and (D) groups, respectively. At 6 weeks post-fasting FBG, TG,
      TC, HDL, and LDL returned to levels indistinguishable from their baseline values
      in both groups, while MDA was maintained significantly lower by (25.7, 22.7%),
      and GSH significantly higher by (26.3, 31.3%), in the (ND) and (D) groups,
      respectively. CONCLUSIONS: Ramadan fasting improves glycemic control and lipids
      profile and alleviates oxidative stress in diabetics.

PMID- 24442383
TI  - Mitigating spinal cord distraction injuries: the effect of durotomy in decreasing
      cord interstitial pressure in vitro.
AB  - STUDY DESIGN: The present study involved an in vitro examination of spinal cord
      interstitial pressure (CIP) during distraction before and after durotomy in three
      spinal cord segments obtained from five pigs. OBJECTIVES: To determine whether
      durotomy can be used to decrease the elevated CIP associated with spinal cord
      distraction. SUMMARY OF BACKGROUND DATA: Spinal cord distraction is a known cause
      of spinal cord injury. Several articles describing the pathophysiology of cord
      distraction injuries suggest that the underlying mechanism of injury is a
      microvascular ischemic event. The authors have previously described an increase
      in CIP with spinal cord distraction, with average pressures of 23 mmHg at loads
      of 1,000 g. To date, there are no published studies that have evaluated the
      efficacy of intentional durotomies as a treatment for elevated CIP. METHODS: A
      total of 15 spinal cord sections were harvested from pigs and distracted while
      immersed in saline, using a fixed 1,000 g distraction force. The CIP decay was
      then measured at 30-s intervals for 10 min. The distraction/relaxation maneuver
      was performed six times with continuous CIP monitoring and was subsequently
      followed by durotomy. RESULTS: The pressure-decay curves were similar for each
      specimen, but varied according to individual pigs and anatomical levels. CIP
      decayed over the first 4 min of distraction and remained constant for the final 6
      min. Longitudinal durotomy led to a dramatic drop in CIP toward baseline and
      appeared to be as effective as transverse durotomy with regard to the
      normalization of pressure. CONCLUSION: Spinal cord distraction causes elevations
      in CIP. Durotomy lowers elevated CIP in vitro and may be effective at lowering
      CIP in vivo. Further study is required to evaluate the usefulness of durotomy in
      vivo.

PMID- 24442384
TI  - Functional evaluation in cruciate-retaining-type TKA: anatomical relationship
      between tibial osteotomy level and PCL attachment.
AB  - INTRODUCTION: The level and morphology of posterior cruciate ligament (PCL)
      attachment vary greatly among individuals, and the function of the PCL after
      tibial osteotomy performed during total knee arthroplasty (TKA) surgery remains
      unclear. Therefore, we evaluated the resection amount of PCL attachment and the
      function of the residual PCL in cruciate-retaining (CR)-type TKA. METHODS: We
      examined 76 patients with knee osteoarthritis who had undergone CR-type TKA. The
      level of the tibial PCL attachment was measured by preoperative MRI and the
      amount resected into the tibial PCL attachment from the osteotomy level as well
      as the longitudinal diameter of the residual PCL by postoperative radiography.
      The relationships between these and joint gap tension value at flexion or amount
      of tibial posterior transfer by postoperative stress radiography were examined.
      RESULTS: The longitudinal diameter of the PCL attachment and the attachment level
      varied widely among patients. There were 39 patients (51%) with tibial osteotomy
      level caudal to the PCL attachment. Flexion gap tension in patients with residual
      PCL (residual PCL group) was slightly higher than those without residual PCL
      (fully-resected group). There was no correlation between amount of PCL residual
      and joint gap tension at the flexion position. Even in those without residual
      PCL, no correlation was observed between the resected amount and flexion joint
      gap tension value. Comparison of amount of posterior transfer by postoperative
      stress radiography between those with and without residual PCL revealed no
      significant difference. CONCLUSIONS: It was confirmed that the level and
      morphology of the PCL attachment vary greatly among individuals and the amount of
      PCL resected at tibial osteotomy during TKA surgery varies depending on the
      patient. The tension due to flexion position tended to decrease if the tibial
      osteotomy line was caudal to the PCL attachment; however, the amount of tibial
      posterior transfer due to stress was not changed.

PMID- 24442385
TI  - Carpal tunnel release in patients with diabetes result in poorer outcome in long
      term study.
AB  - BACKGROUND: The aim of this prospective study was to compare the results of
      surgical decompression of carpal tunnel syndrome (CTS) in patients with diabetes
      mellitus with those with idiopathic CTS. METHODS: The results of surgical
      decompression of CTS in 27 patients with diabetes mellitus were compared with 42
      patients with idiopathic CTS. All patients underwent surgical release of
      transverse carpal ligament by the mini-incision of palm technique. Patient self
      administered Boston Questionnaire (BQ) for the assessment of severity of CTS
      symptoms and hand functional status was evaluated before and 6 months and 10
      years after surgery. RESULTS: After surgical release, all the patients of both
      groups reported an absence of pain, disappearance or reduction of paresthesia,
      and improvement in hand function. Six months after surgery, there was a
      significant improvement of symptomatic and functional BQ scores compared with
      preoperative state in both groups. Ten years after surgery, there was statistical
      difference in preoperative and postoperative 10th year functional BQ score
      between DM (-) and DM (+) (p < 0.01). DM status affected statistically functional
      BQ score between preoperative and postoperative 10th year. CONCLUSION: Diabetes
      mellitus was a risk factor for poor outcome of surgical decompression of CTS.
      Patients with diabetes had worse surgical outcome compared with patients with
      idiopathic CTS in long-term follow-up.

PMID- 24442386
TI  - Impact of respiratory motion correction and spatial resolution on lesion
      detection in PET: a simulation study based on real MR dynamic data.
AB  - The aim of this study is to investigate the impact of respiratory motion
      correction and spatial resolution on lesion detectability in PET as a function of
      lesion size and tracer uptake. Real respiratory signals describing different
      breathing types are combined with a motion model formed from real dynamic MR data
      to simulate multiple dynamic PET datasets acquired from a continuously moving
      subject. Lung and liver lesions were simulated with diameters ranging from 6 to
      12 mm and lesion to background ratio ranging from 3:1 to 6:1. Projection data for
      6 and 3 mm PET scanner resolution were generated using analytic simulations and
      reconstructed without and with motion correction. Motion correction was achieved
      using motion compensated image reconstruction. The detectability performance was
      quantified by a receiver operating characteristic (ROC) analysis obtained using a
      channelized Hotelling observer and the area under the ROC curve (AUC) was
      calculated as the figure of merit. The results indicate that respiratory motion
      limits the detectability of lung and liver lesions, depending on the variation of
      the breathing cycle length and amplitude. Patients with large quiescent periods
      had a greater AUC than patients with regular breathing cycles and patients with
      long-term variability in respiratory cycle or higher motion amplitude. In
      addition, small (less than 10 mm diameter) or low contrast (3:1) lesions showed
      the greatest improvement in AUC as a result of applying motion correction. In
      particular, after applying motion correction the AUC is improved by up to 42%
      with current PET resolution (i.e. 6 mm) and up to 51% for higher PET resolution
      (i.e. 3 mm). Finally, the benefit of increasing the scanner resolution is small
      unless motion correction is applied. This investigation indicates high impact of
      respiratory motion correction on lesion detectability in PET and highlights the
      importance of motion correction in order to benefit from the increased resolution
      of future PET scanners.

PMID- 24442387
TI  - Thymoma with osseous metaplasia in an adolescent.
AB  - A 13-year-old girl was incidentally found to have a partially calcified anterior
      mediastinal mass during the work-up for a left humeral lesion. The resected
      specimen demonstrated a lymphocyte predominant World Health Organization type B1
      thymoma with nodules of metaplastic bone consistent with osseous metaplasia. In
      addition, she had multiple osteochondromas, a periosteal chondroma of the
      humerus, a metaplastic osseous pseudotumor of the thigh, and other benign
      appearing sclerotic foci, all manifestations of what is likely an autosomal
      dominant disorder. 

PMID- 24442388
TI  - Disc-electrophoresis of proteins and enzymes from styles, pollen and pollen tubes
      of self-incompatible cultivars ofLilium longiflorum.
AB  - Lilium longiflorum possesses several advantages for investigating the nature of
      self-incompatibility. The large hollow styles permit analyses of proteins and
      enzymes from pollen tubes removed from the styles after selfing or crossing along
      with their corresponding styles, as well as from pollen grains and from styles of
      unpollinated flowers. Biochemical methods have been developed for protein
      extractions and subsequent analyses by disc electrophoresis. These techniques
      have been used to demonstrate changing protein and esterase patterns in pollen
      and styles from four cultivars. No apparent association between the self
      incompatibility reaction and proteins which migrate at pH 8.3 in 71/2% acryamide
      gel was noted. These analyses included soluble proteins, esterases, peroxidases
      and several dehydrogenases. 

PMID- 24442389
TI  - [Investigations on gigas mutants ofOenothera berteriana andOenothera odorata].
AB  - 1. Seedlings of the following Oenotherae were treated with colchicine:Oe.
      berleriana (B.l),Oe. odorata (v.l), a B.l with plasma ofodorata and plastids
      ofberteriana, a v.I with plasma and plastids ofBerteriana, and B.I andl.v
      obtained from reciprocal crossings of B.l x (x) v.I, selfed over and over again.
      2. The gigas mutants thus obtained had the characteristics described previously.
      It is remarkable that those differences caused by plasma and plastids in the
      diploid pairs serving for comparison could also be demonstrated in the
      corresponding tetraploid forms. 3. The Bl.vI obtained from crossings B.l 4 n*v.I
      4 n showed that in B.l 4 n there is predominantly a production of B.l sexual
      cells, and in v.I 4 n a production of v.I sexual cells. A BI.lv identical with
      Bl.vI was obtained from the cross B.I 4 n*l.v 4 n. 4. Part of the seedlings from
      v.I 4 n*B.l 4 n were variegated. Thusberteriana-plastids capable of becoming
      green were transferred by the Bl pollen tubes. Because of the odorata plastids
      which can not grew fully green, the leaves of this vI.Bl very much resembled
      those of v.I 4 n. 5. Pictures of the pollen showed that the genetic constitution
      of the tetraploids and triploids producing the pollen grains helps to determine
      the number of their pores. 6. Cytological studies showed that there is
      surprisingly often a normal 14+14 distribution of the 28 chromosomes during
      meiosis in the tetraploid forms. This results in the high degree of constancy
      obtained from selfing. Yet to be studied is how this predominantly normal
      distribution of chromosomes is accomplished. 

PMID- 24442390
TI  - Sex chromosome replication and sex chromatin inAkodon azarae (Rodentia
      Cricetidae).
AB  - Sex chromosome length, sex chromatin area and the pattern of sex chromosome
      replication were determined in the field mouseAkodon azarae (Rodentia
      Cricetidae). Among the animals studied a group of spontaneously deleted females
      was included. The complemont in deleted females was 38Xx, being the x a grossly
      deleted X-chromosome.Length of sex chromosomes expressed as percentage of the
      haploid set was: X-chromosome 7.89% (+/-1.18), x-chromosome 1.47% (+/-0.20), Y
      chromosome 1.15% (+/-0.29). Area of sex chromatin expressed as percentage of the
      haploid genome was 7.28% (+/-1.18) in XX females and 3.26% (+/-0.73) in Xx
      females. According to these data it was assumed that: (a) sex chromatin was
      formed by all those sex chromosome material in excess of the 5% of the haploid
      set; (b) the x-chromosome in Xx females was always involved in sex chromatin
      formation.Time-sequence of sex chromosome replication was as follows: (a) at the
      beginning of the S period one X-chromosome starts replication carly while the
      other X, the x and the Y-chromosomes are the last to initiate DNA synthesis; (b)
      in the intermediate stage of the S period sex chromosomes replicate in the same
      way as autosomes; (c) in late and final stages of the S period both sex
      chromosomes are late replicating in their whole extension. It is concluded that
      the pattern of sex chromosome replication at the beginning of the S period may be
      more informative than the pattern at the end of the S phase to distinguish
      between hetero-and euchromatin in the sex genome ofAkodon azarae. 

PMID- 24442391
TI  - [The coordination of the locus R (hypocotyl colour) of sugar beet to chromosome
      II].
AB  - By means of trisomics the linkage group containing R (hypocotyl colour), B
      (bolting without vernalization) and other known loci was shown to lie in
      chromosome II (numbering afterBUTTERFASS 1964). Whether random chromatid
      assortment in R is involved could not be established with certainty. 

PMID- 24442392
TI  - Growth ofTrifolium pratense L. pollen tubes in compatible and incompatible styles
      of excised pistils.
AB  - The stigma and style portions of red clover pistils were culturedin vitro after
      cross- (genetically compatible) or self- (incompatible) pollination. Pollen tubes
      grew through styles in which they were compatible and, in some treatments,
      through styles which were incompatible.Boric acid, calcium nitrate and a
      carbohydrate in the medium, and moderate-to-cool temperatures generally enhanced
      pollen tube growth of compatible and incompatible matings. Several plant hormones
      at high concentrations inhibited pollen growth with compatible matings and did
      not retard the incompatibility mechanism. Application of high temperatures to the
      flower heads during the period of anthesis retarded the incompatibility
      mechanism. This temperature treatment affected the styles and not the pollen. In
      one of three experiments the application of relatively large amounts of pollen to
      the stigma rendered the incompatibility mechanism less effective. 

PMID- 24442393
TI  - Genotype-environment interaction for awn development in isogenic lines of barley.
AB  - Awn length of four isogenic lines of barley differing by two genes for awn
      development (A andB) and their short iinkage blocks was evaluated at a wide range
      of plant densities (0.002 to 3.345 m(2)/plant) for two years. Awn development was
      reduced at high plant density. The quarter-awned genotype (aaBB) became
      phenotypically awnless (aabb) at high plant density. Similar results were
      obtained each year and the genotype x plant density effect was the major portion
      of the genotype-environment interaction variance. Additive (alpha A , alpha B )
      and additive x additive (alpha AB ) gene effects were computed for each plant
      density for lateral and central floret awn length. For lateral awns alpha AB was
      not affected, but alpha A and alpha B increased with decreased plant density. In
      contrast, for central awns alpha A and alpha AB decreased and alpha B increased
      with decreased plant density.Central floret awns measured at each spike node
      showed that high plant density reduced awn development most in the lower half of
      the spike. This is the zone of most rapid awn differentiation and since culm
      elongation and spike growth rates were greatly increased by high plant density,
      it was suggested that rapid growth invoked a stress on awn development and
      differentially altered the expression ofA andB. 

PMID- 24442394
TI  - Quantitative genetics of sugarcane : I. Analysis of variation in a commercial
      hybrid sugarcane population.
AB  - 1. The statistical techniques of quantitative genetic analysis have been applied
      to the study of variation in a sugarcane breeding population of interspecific
      hybrid origin. 2. A comparison has been made of estimates of heritability based
      on sire or dam components of variance alone. The overall equality of these two
      statistics has been taken as evidence that pollen contamination, self
      fertilization and parthenogenetic reproduction are unimportant sources of
      disturbance in the genetic analysis of the population. 3. From an analysis of
      plot means it has been concluded that all twenty-four primary characters show
      significant clonal variation, the overall mean value for clonal repeatability
      being 0.48. For sixteen of the variables, the estimate of heritability based on
      the component of variance among full-sib family groups was also significant, the
      mean value of this parameter being 0.29. 4. For ten of the primary characters,
      the estimate of clonal repeatability differed significantly from the estimate of
      heritability. In every case the repeatability value was the greater of the two.
      It cannot be concluded that nonadditive genetic variance is the major factor
      responsible, since the use of selected clones as parental material, and
      disassortative mating for some easily observed characters, appear to provide a
      sufficient explanation of the disparity. 5. The irregular transmission of
      unpaired chromosomes derived fromS. spontaneum, S. robustum andS. sinense may
      possibly contribute to the observed difference between heritability and
      repeatability. No other serious departure was observed from expectations based on
      diploid inheritance. 6. The analyses show fibre percent fresh weight and sucrose
      percent dry matter to be particularly strong clonal characters. The measure of
      sucrose per plot, which includes variability for yield of cane, has a
      heritability of 0.24, a repeatability of 0.43, and a high coefficient of
      variation (46%). 7. Comparisons of the breeding population with two commercial
      standards have indicated that selection among genotypes within the present
      population could lead to significant improvement in any one of the commercially
      important characters. Further gains with subsequent cycles of hybridization and
      selection are also strongly indicated. No information has as yet been obtained on
      the magnitude of genotype*years interaction effects. 

PMID- 24442395
TI  - A male sterile pepper (C. annuum L.) mutant.
AB  - 1. After treatment of dry seeds of red pepperCapsicum annuum L. with X-rays a
      male-sterile mutant was discovered in the M2. 2. The male-sterile mutant
      segregates in a ratio of 3.28:1 (chi(2)=3.148, probability 0.07). 3. After an
      alternative cultivation of male-sterile plants and of a variety with good
      combining ability relatively good fruit-setting and seed production was obtained.
      4. Grafting of male-sterile scions to normal stocks does not affect the male
      sterile phenotype. 

PMID- 24442396
TI  - [Self-fertility and intra-clonal fertility in alfalfa].
AB  - In comparison with self-pollination of alfalfa flowers fertility increased with
      geitonogamy to intraclonal pollination; the number of seeds per pod and seed size
      were also favourably influenced. Plasma differentiation may be the reason.
      Methodical aspects of genetic and breeding studies are discussed. 

PMID- 24442398
TI  - Co-suppression of synthesis of major alpha-kafirin sub-class together with gamma
      kafirin-1 and gamma-kafirin-2 required for substantially improved protein
      digestibility in transgenic sorghum.
AB  - KEY MESSAGE: Co-suppressing major kafirin sub-classes is fundamental to improved
      protein digestibility and nutritional value of sorghum. The improvement is linked
      to an irregularly invaginated phenotype of protein bodies. ABSTRACT: The combined
      suppression of only two genes, gamma kafirin-1 (25 kDa) and gamma-kafirin-2 (50
      kDa), significantly increases sorghum kafirin in vitro digestibility. Co
      suppression of a third gene, alpha-kafirin A1 (25 kDa), in addition to the two
      genes increases the digestibility further. The high-digestibility trait has
      previously only been obtained either through the co-suppression of six kafirin
      genes (alpha-A1, 25 kDa; alpha-B1, 19 kDa; alpha-B2, 22 kDa; gamma-kaf1, 27 kDa;
      gamma-kaf 2, 50 kDa; and delta-kaf 2, 18 kDa) or through random chemical-induced
      mutations (for example, the high protein digestibility mutant). We present
      further evidence that suppressing just three of these genes alters kafirin
      protein cross-linking and protein body microstructure to an irregularly
      invaginated phenotype. The irregular invaginations are consistent with high
      pepsin enzyme accessibility and hence high digestibility. The approach we adopted
      towards increasing sorghum protein digestibility appears to be an effective tool
      in improving the status of sorghum as a principal supplier of energy and protein
      in poor communities residing in marginal agro-ecological zones of Africa.

PMID- 24442399
TI  - Letter to the editor, "Tooth loss in aggressive periodontitis: a systematic
      review".

PMID- 24442400
TI  - Response to letter to the editor, "Tooth loss in aggressive periodontitis: a
      systematic review".

PMID- 24442397
TI  - Recent progress on molecular breeding of rice in China.
AB  - Molecular breeding of rice for high yield, superior grain quality, and strong
      environmental adaptability is crucial for feeding the world's rapidly growing
      population. The increasingly cloned quantitative trait loci and genes, genome
      variations, and haplotype blocks related to agronomically important traits in
      rice have provided a solid foundation for direct selection and molecular
      breeding, and a number of genes have been successfully introgressed into mega
      varieties of rice. Here we summarize China's great achievements in molecular
      breeding of rice in the following five traits: high yield, biotic stress
      resistance, abiotic stress resistance, quality and physiology. Further, the
      prospect of rice breeding by molecular design is discussed. 

PMID- 24442401
TI  - Pharmacological treatment of acromegaly: its place in the overall therapeutic
      approach.

PMID- 24442402
TI  - Radiologic and histologic consequences of radiosurgery for brain tumors.
AB  - Progressively enlarging encephalopathic changes are now well-documented effects
      of gamma knife radiosurgery (GKRS) occurring ~3-30 months after treatment of both
      benign and malignant brain lesions. These changes can be variably associated with
      inflammatory demyelination and necrosis and/or recurrent tumor. While
      radiographic differentiation between encephalopathic changes and recurrent tumor
      is of high clinical relevance, confident interpretation of post-radiosurgery
      imaging changes can be challenging or even impossible in some cases. Gadolinium
      enhanced MRI of these lesions reveals variable amounts of enhancing and non
      enhancing components within these lesions that have not been clearly correlated
      with structural-pathologic change. The goal of this study is to characterize the
      histopathological changes associated with enhancing versus non-enhancing regions
      of GKRS-treated lesions. MRI images of patients with progressive, etiologically
      ambiguous brain lesions following GKRS were reviewed prior to explorative
      neurosurgery. Chosen for this study were lesions in which distinct areas of
      enhancement and non-enhancement of at least 5 mm in size could be identified (n =
      16). Distinctly enhancing and non-enhancing areas were separately biopsied and
      histologically evaluated. Only cases with uniform histological results are
      presented in this study. Enhancing and non-enhancing areas in post GKRS lesions
      represent separate pathological changes. Radiographically enhancing areas
      correlate either with recurrent tumor growth or inflammatory demyelinating
      changes. Lack of radiographic enhancement correlates with coagulative necrosis if
      the sample is taken from the center of the lesion, or with reactive astrocytosis
      if the sample is taken from the periphery. Separate biopsy of enhancing and non
      enhancing regions of post-GKRS encephalopathy was able to confirm that the
      pathologies in these areas are distinct. These findings allow for better-informed
      correlation of histological and radiological changes and a better understanding
      of post-treatment tissue pathology.

PMID- 24442404
TI  - [Trypsin inhibitors and proteolytic activities of the albumins in seeds of Vigna
      unguiculata].
AB  - The presence of trypsin inhibitors is demonstrated in cotyledonary albumins of
      Vigna unguiculata by cross-electrophoresis against trypsin and by kinetic
      measurements. These inhibitors are isolated by selective trapping on insoluble
      trypsin. On the other hand, evidence is given showing that cotyledonary albumins
      hydrolyse alpha-N-benzoyl-DL-arginine-p-nitroanilide (BAPA) and casein. Purified
      trypsin-inhibitors partially inhibit the caseolytic activity of albumins but do
      not influence their hydrolytic activity toward BAPA. A partial characterisation
      of proteases and inhibitors is carried out. A model for the regulation of the
      proteolytic activities of the seeds by trypsin inhibitors is suggested. 

PMID- 24442403
TI  - Adherence and delivery: implementation quality and program outcomes for the
      seventh-grade keepin' it REAL program.
AB  - Poor implementation quality (IQ) is known to reduce program effects making it
      important to consider IQ for evaluation and dissemination of prevention programs.
      However, less is known about the ways specific implementation variables relate to
      outcomes. In this study, two versions of keepin' it REAL, a seventh-grade drug
      prevention intervention, were implemented in 78 classrooms in 25 schools in rural
      districts in Pennsylvania and Ohio. IQ was measured through observational coding
      of 276 videos. IQ variables included adherence to the curriculum, teacher
      engagement (attentiveness, enthusiasm, seriousness, clarity, positivity), student
      engagement (attention, participation), and a global rating of teacher delivery
      quality. Factor analysis showed that teacher engagement, student engagement, and
      delivery quality formed one factor, which was labeled delivery. A second factor
      was adherence to the curriculum. Self-report student surveys measured substance
      use, norms (beliefs about prevalence and acceptability of use), and efficacy
      (beliefs about one's ability to refuse substance offers) at two waves (pretest,
      immediate posttest). Mixed model regression analysis which accounted for missing
      data and controlled for pretest levels examined implementation quality's effects
      on individual level outcomes, statistically controlling for cluster level
      effects. Results show that when implemented well, students show positive outcomes
      compared to students receiving a poorly implemented program. Delivery
      significantly influenced substance use and norms, but not efficacy. Adherence
      marginally significantly predicted use and significantly predicted norms, but not
      efficacy. Findings underscore the importance of comprehensively measuring and
      accounting for IQ, particularly delivery, when evaluating prevention
      interventions. 

PMID- 24442405
TI  - A study of potassium gradients in the epidermis of intact leaves of Commelina
      communis L. in relation to stomatal opening.
AB  - Potassium sensitive microelectrodes have been used to determine the potassium
      content of individual epidermal cells in intact leaves of C. communis L. Large
      gradients of potassium across the stomatal complex were observed. When the
      stomata were open a stepwise decrease in vacuolar potassium content from the
      guard cells outwards was found. With the stomata closed a gradient in the
      opposite direction was observed, with the potassium content of the guard cells
      much lower than that of the surrounding cells. Electrical potential differences
      between the cells were determined enabling driving forces on potassium to be
      calculated. The results indicate that the potassium gradients are maintained
      against the electrochemical gradient and that potassium transport both into and
      out of the guard cells is an active process. Potassium transport between the
      subsidiary cells also appears to be active.Potassium fluxes into the guard cell
      during stomatal opening were calculated and found to be relatively high. The
      implications of this are discussed. 

PMID- 24442406
TI  - Rapid growth responses of corn root segments: Effect of pH on elongation.
AB  - The effect of pH on the elongation rate of 2-mm-long subapical segments from corn
      roots (Zea mays L.) was investigated under aerobic (O2) and anaerobic (N2)
      conditions using a specially designed apparatus. The maximum elongation rate was
      obtained with a citrate-phosphate buffered solution of pH 3.4 or a non-buffered
      solution of pH 3.2. Acid stimulation of the elongation rate occurred in the zone
      of maximum elongation in the root, the 3 mm region 1 mm behind the apex. The acid
      response can be rapidly and repeatedly reinitiated by alternating between pH 4.0
      and 7.0 media. Low pH can increase the elongation rate under N2 conditions, but
      the response is only ca. 50% that of the increase observed under O2 conditions.
      Reinitiation of the acid response does not occur when solutions are gassed with
      N2. The data suggest that the response of root segments to H ions is similar to
      that reported in the literature for shoot tissue. However, the magnitude of the
      root response is much higher than that of shoot tissue. Also, there is evidence
      that some aspects of the mode of action of H ions on wall loosening in root
      tissue may differ from that in shoot tissue. Corn root segments, though lacking a
      cuticle, do not respond to low pH in the manner reported for peeled stem tissue,
      the cuticle and epidermis of which have been removed. For these reasons rapid
      growth responses of roots and shoots may not be strictly comparable. 

PMID- 24442407
TI  - Digestive enzymes secreted by the carnivorous plant Nepenthes macferlanei L.
AB  - At least two proteases are present in the secretion of the pitchers of Nepenthes
      macferlanei, a major one with an estimated molecular weight of 59000 and a minor
      one of 21000. The specificity of the major enzyme, nepenthesin, was broader than
      previously reported, and strikingly similar to that of pepsin. Lipase activity
      was also demonstrated, while no amylase activity was present. 

PMID- 24442408
TI  - Light-triggered membrane potential oscillations and electric coupling in
      variegated photosynthetic mutants of Oenothera.
AB  - Light-triggered transient oscillations of the membrane potential are recorded
      with glass micro-electrodes in mesophyll cells of Oenothera. These transients are
      absent in leaf samples prepared from variegated plastome mutants of Oenothera, in
      which all cells have a genetically impaired photosystem I or photosystem II. This
      suggests that co-operation between the two photosystems is responsible for the
      induction of the transients. Transients are observed in mutated cells when the
      illuminated leaf sample also comprises normally green cells and there is a
      symplasmatic connection between the two types of cells. This phenomenon of
      electric coupling between neighbouring cells is discussed in view of the concept
      of symplasmatic transport. 

PMID- 24442409
TI  - Daily changes in carbon-dioxide exchange and photosynthate translocation of
      leaves of Vicia faba.
AB  - Net carbon-dioxide exchange and loss of photosynthate-(14)C from leaves of Vicia
      faba L. were estimated throughout a day (16/8 h light/dark periods) by infrared
      gas analysis and Geiger-Muller-tube monitoring, respectively. Net photosynthesis
      reached 95% of the mean maximum rate within 1 h of the start of the photoperiod,
      and thereafter remained relatively constant before declining during the last 2-4
      h of the photoperiod. Respiration was highest at the start of the dark period.
      The loss of photosynthate-(14)C from leaves exhibited two phases: a rapid phase
      which was fastest but shortest following (14)C incorporation in the middle of the
      photoperiod, and a slower phase of much longer duration. Absolute rates of (14)C
      loss exhibited diurnal trends reaching 95% of the maximum 6 h after the start of
      the photoperiod and remaining high until darkness, and then declined markedly. Of
      the total carbon fixed in one 24 h period, about 50% was lost during the current
      photoperiod, 14% during the dark period and 5% during the next photoperiod. The
      estimated amount of carbohydrate remaining within the leaf followed a diurnal
      pattern of accumulation and depletion. The daily course of translocation was not
      closely related to that of net photosynthesis or carbohydrate concentration. 

PMID- 24442410
TI  - [Studies on the association of 5-dehydroquinate hydro-lyase and shikimate:
      NADP(+)-oxidoreductase in higher plants].
AB  - The properties of two enzymes involved in the shikimic acid pathway,
      dehydroquinate hydro-lyase and shikimate: NADP(+) oxidoreductase were studied in
      different species of higher plants (pteridophytes, gymnosperms, angiosperms)
      using chromatography on Sephadex G 100, DEAE cellulose, hydroxylapatite and
      isoelectric focusing.The two enzymes were not separable by these methods, and we
      conclude that they exist as an aggregate in higher plants. Moreover, the
      behaviour of the complex is sometimes quite different according to the species,
      and these data support the notion of alloenzymes.This situation seems contrary to
      that found in procaryotic organisms in which all the enzymes of the pathway are
      separable and in fungi in which five enzymes are associated.These results are
      discussed in relation to evolution, the channeling function of such complexes and
      the metabolism of quinic acid in plants. 

PMID- 24442411
TI  - An action spectrum for photoinduction of pileus formation in a basidiomycete,
      Favolus arcularius.
AB  - The action spectrum for photoinduction of pileus formation in Favolus arcularius
      (Fr.) Ames. shows four maxima, at ca. 375-385, 420, 446, and 480 nm, and minima
      near 365, 400, 435, and 470 nm. Wavelengths above 510 nm were ineffective. The
      maxima coincided with four of the six maxima for primordium formation of this
      fungus, but the two maxima for the latter around 398 and 514 nm could not be
      detected. The photosensitive region for the initiation of pileus formation was
      localized in the apical region of the stipes. 

PMID- 24442413
TI  - Kinetic modeling of riboflavin biosynthesis in Bacillus subtilis under production
      conditions.
AB  - To study the network dynamics of the riboflavin biosynthesis pathway and to
      identify potential bottlenecks in the system, an ordinary differential equation
      based model was constructed using available literature data for production
      strains. The results confirmed that the RibA protein is rate limiting in the
      pathway. Under the conditions investigated, we determined a potential limiting
      order of the remaining enzymes under increased RibA concentration (>0.102 mM) and
      therefore higher riboflavin production (>0.045 mmol g(CDW)(-1) h(-1) and 0.0035
      mM s(-1), respectively). The reductase activity of RibG and lumazine synthase
      (RibH) might be the next most limiting steps. The computational minimization of
      the enzyme concentrations of the pathway suggested the need for a greater RibH
      concentration (0.251 mM) compared with the other enzymes (RibG: 0.188 mM, RibB:
      0.023 mM).

PMID- 24442412
TI  - The significance of YKL-40 protein in liver fibrosis.
AB  - OBJECTIVE: The aims of this review are to describe the present knowledge about
      YKL-40 protein, discuss its relation to liver fibrosis, and to look ahead at
      future perspectives of YKL-40 research. INTRODUCTION: Liver fibrosis is
      characterized by excess collagen deposition, decreased extracellular matrix
      degradation and activation of hepatic stellate cells. Therefore, advancement in
      the identification of liver fibrosis biomarkers with diagnostic and prognostic
      values becomes an important tool for future molecular therapy. The molecular
      basis of YKL-40 in liver fibrosis is unknown. METHODS: A PubMed database search
      was performed for studies of YKL-40 in liver injury and fibrosis. RESULTS AND
      CONCLUSIONS: YKL-40 is an inflammatory glycoprotein involved in endothelial
      dysfunction by promoting chemotaxis, cell attachment and migration,
      reorganization, and tissue remodeling as a response to endothelial damage.
      Several studies demonstrate that elevated serum YKL-levels are independently
      associated with the presence of endothelial damage and even higher YKL-40 levels
      are documented in liver fibrosis. YKL-40 may play a key role in liver injury and
      fibrosis.

PMID- 24442414
TI  - Off-label use of a reversed flared endurant iliac limb stengraft for the
      management of a life-threatening internal iliac artery aneurysm rupture.
AB  - We report a case of a life-threatening internal iliac artery aneurysm rupture
      managed successfully with an on-table reversed flared iliac limb stentgraft and
      embolization. This easily off-the-shelf reproducible technique avoids using a
      more complex and expensive bifurcated aorto-iliac graft and could be a good
      solution in emergency situation where a custom graft is not available. 

PMID- 24442415
TI  - Absence of the right common carotid artery: Doppler ultrasonographic and MR
      angiographic findings.
AB  - We present a case of common carotid artery agenesis which is an extremely rare
      congenital anomaly. Less than 35 cases have been reported. These anomalies are
      typically asymptomatic and usually discovered as an incidental finding. Color
      Doppler ultrasonography is an effective and sensitive method for detecting
      absence of common carotid artery. But it is insufficient to identify the anomaly
      as a whole. Magnetic resonance angiography is a complementary technique to
      describe the origin of the external carotid artery and internal carotid artery. 

PMID- 24442416
TI  - Chelator-induced phytoextraction of zinc and copper by rice seedlings.
AB  - Solution culture was carried to investigate capacity of synthetic
      aminopolycarboxylic acids (ethylenediamine tetraacetate, N
      hydroxyethylenediaminetriacetic acid, and diethylenetriamine-pentaacetate) for
      enhancing botanical removal and transport of heavy metals (Cu and Zn) by plants.
      Biodegradable organic acids (citric acid, malic acid, and oxalic acid) were also
      selected as alternatives to compare them with synthesized chelating agents for
      effectiveness. Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in
      nutrient solutions treated with single or combined metal solutions in presence or
      absence of chelating compounds. Calculation by chemical equilibrium program
      VISUAL MINTEQ showed that different chelating compounds had various complex
      potential with Cu(2+) and Zn(2+) ions, in which synthetic chelators exhibited
      higher complexed capability than biodegradable organic acids. All applied
      synthetic aminopolycarboxylic acids significantly decreased removal of metal from
      nutrient solution (p < 0.01), while more or less effects of organic acids
      supplied on biosorptive potential were observed with all treatments (p > 0.05),
      compared with the treatment without metal ligands. Synthetic aminopolycarboxylic
      acids significantly decreased metal concentrations in plant materials in all
      treatments (p < 0.01). However, biodegradable organic acids decreased metal
      concentrations in roots (p < 0.01), but enhanced them in shoots (p < 0.01).
      Results obtained indicated that synthetic aminopolycarboxylic acids decreased
      uptake of metals by rice seedlings, but translocation of metals complexed within
      plant materials was evident. Although exogenous biodegradable organic acids
      showed negligible effect on botanical removal of metals, metals complexed with
      organic acids was more mobile than those complexed with other chelating agents.
      These information collected here had important implication for the use of
      biodegradable metal chelators in transport of essential micronutrients in plant
      nutrition.

PMID- 24442417
TI  - Genome-wide copy number variation study and gene expression analysis identify
      ABI3BP as a susceptibility gene for Kashin-Beck disease.
AB  - Kashin-Beck disease (KBD) is a chronic osteochondropathy. In this study, we
      conducted the first genome-wide copy number variation study (GCNVS) of KBD
      totally involving 2,743 Chinese Han adults. GCNVS was first performed using
      Affymetrix Human SNP6.0 Arrays. The identified copy number variations (CNVs) were
      then replicated in an independent Chinese Han sample containing 1,026 subjects.
      SNP genotyping, CNV identification and quality control were implemented by
      Birdsuite. STRUCTURE and EIGENSTRAT were applied for controlling potential
      population stratification in the GCNVS. Association analysis was conducted using
      PLINK. Microarray and qRT-PCR were also conducted to compare the expression
      levels of the genes overlapping with identified CNVs between KBD patients and
      healthy controls. GCNVS found that CNV452 (P value = 7.78 * 10(-5)) overlapping
      with ABI3BP gene was significantly associated with KBD. Replication association
      study observed that rs9850273 (P value = 0.008) and rs7613610 (P value = 0.021)
      in ABI3BP gene were significantly associated with KBD. Gene expression analysis
      also found that ABI3BP was up-regulated in KBD patients compared to healthy
      controls. Our results suggest that ABI3BP was a novel susceptibility gene for
      KBD.

PMID- 24442419
TI  - One-year adjustable intragastric balloons: results in 73 consecutive patients in
      the U.K.
AB  - BACKGROUND: Most intragastric balloons have 6-month approval. We report results
      with the Spatz Adjustable Balloon: approved for 12 months and adjustable.
      METHODS: Seventy-three patients (mean: age 45.5; weight 114.5 kg; BMI 36.6 kg/m2)
      scheduled for 1-year implantation with Spatz balloon (mean volume 417 ml saline).
      Adjustments performed for early intolerance and weight loss plateau. RESULTS:
      Three patients failed insertion. There were 21 early removals (4 intolerant
      refusing adjustment; 3 deflations; 14 satisfied patients) leaving 49 patients at
      12 months. Results of 70 patients (49 patients at 12 months and 21 patients at
      <12 months) were a mean 21.6 kg weight loss; 19% weight loss; and 45.7% EWL
      (excess weight loss). Ten intolerant patients were adjusted and lost additional
      mean 13.2 kg. Fifty-one patients with weight loss plateau scheduled for
      adjustment: adjustments failed in 6 and non-response in 7. The adjusted 38
      patients lost an additional mean 9.4 kg and at extraction had mean 40.9% EWL with
      18.7% weight loss. Three catheter impactions required surgical extraction, and
      three deflated balloons didn't migrate beyond stomach. CONCLUSIONS: The Spatz
      balloon is an effective procedure without mortality; however, it carries a risk
      of catheter impaction necessitating surgical extraction (4.1%). The failure rate-
      4.1%; intolerance without ability to adjust balloon--5.5%; major complications
      occurred in 3 (4.1%); minor (balloon deflations) in 3 (4.1%), and 2 asymptomatic
      gastric ulcers at extraction (2.7%). The longer implantation period and
      adjustment option combine to produce greater weight loss, albeit <10% weight loss
      beyond the pre-adjustment weight loss.

PMID- 24442420
TI  - Outcomes of laparoscopic sleeve gastrectomy in patients older than 60 years.
AB  - BACKGROUND: Morbidity and mortality following laparoscopic sleeve gastrectomy
      (LSG) occur at acceptable rates, but its safety and efficacy in the elderly are
      unknown. METHODS: A retrospective review was performed of all patients aged >60
      years who underwent LSG from 2008 to 2012. These patients were 1:2 matched, by
      gender and body mass index (BMI) to young patients, 18 < age < 50. Data analyzed
      included demographics, preoperative and postoperative BMI, postoperative
      complications, and improvement or resolution of obesity-related comorbidities.
      RESULTS: Fifty-two morbid obese patients older than 60 years underwent LSG (mean
      age, 62.9 +/- 0.3 years). These were matched to 104 young patients, age 18-50
      years (mean age, 35.7 +/- 0.8 years). Groups did not differ in male gender (44
      vs. 43%, p = 0.9), preoperative BMI (42.6 +/- 0.7 vs. 42.6 +/- 0.6, p = 0.97),
      and length of follow-up (17 +/- 2 vs. 22 +/- 1.4 months, p = 0.06). Obesity
      related comorbidities were significantly higher in the older group (96 vs. 65%, p
      < 0.001). Excess weight loss (EWL) was higher in the younger group (75 +/- 2.4
      vs. 62 +/- 3%, p = 0.001). Older patients had a significantly higher rate of a
      concurrent hiatal hernia repair (23 vs. 1.9%, p < 0.001). Overall postoperative
      minor complication rate was higher in the older group (25 vs. 4.8%, p < 0.001).
      This included atrial fibrillation (9.5%), urinary tract infection (7%), trocar
      site hernia (4%), dysphagia, surgical site infection, bleeding, bowel
      obstruction, colitis, and nutritional deficiency (2%, each). No perioperative
      mortality occurred. Comorbidity resolution or improvement was comparable between
      groups (88 vs. 80%, p = 0.13). CONCLUSIONS: LSG is safe and very efficient in
      patients aged >60, despite higher rates of perioperative comorbidities.

PMID- 24442418
TI  - The genetic basis of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare disease characterized by
      distinctive changes in pulmonary arterioles that lead to progressive elevation of
      pulmonary artery pressure, pulmonary vascular resistance, right ventricular
      failure, and a high mortality rate. The etiology of PAH is heterogeneous and
      incompletely understood. Based on clinical classification, WHO Group 1 PAH
      includes sporadic disease (idiopathic PAH), inherited PAH (heritable PAH), and
      association with certain medical conditions (associated PAH). Genes play an
      important role in idiopathic and heritable PAH. Mutations in bone morphogenetic
      protein receptor 2 (BMPR2), a member of the transforming growth factor beta
      (TGFbeta) superfamily of receptors, have been identified in 70 % of cases of
      familial PAH, as well as in 10-40 % of cases of idiopathic PAH. Mutations in ALK
      1, ENG, SMAD4 and SMAD8, other TGFbeta family members, are additional rare causes
      of PAH. CAV1 regulates SMAD2/3 phosphorylation, and mutations in CAV1 are a rare
      cause of PAH. KCNK3 is a member of the two-pore domain potassium channels
      expressed in pulmonary artery smooth muscle cells, and mutations in KCNK3 are a
      rare cause of both familial and IPAH. The genetics of PAH are complex due to
      incomplete penetrance and genetic heterogeneity. In addition to rare mutations as
      a monogenic cause of HPAH, common variants in cerebellin 2 (CBLN2) increase the
      risk of PAH by approximately twofold. PAH in children is much more heterogeneous
      than in adults and can be associated with several genetic syndromes, specifically
      syndromes with congenital heart disease, vascular disease, and hepatic disease.
      Clinical genetic testing is available for PAH and should be considered in
      families to allow for more definitive risk stratification and allow for
      reproductive planning. 

PMID- 24442421
TI  - Greater weight loss with the omega loop bypass compared to the Roux-en-Y gastric
      bypass: a comparative study.
AB  - BACKGROUND: Despite similar initial results on weight loss and metabolic control,
      with a better feasibility than the Roux-en-Y gastric bypass (RYGBP), the omega
      loop bypass (OLB) remains controversial. The aim of this study was to compare the
      short-term outcomes of the laparoscopic OLB versus the RYGBP in terms of weight
      loss, metabolic control, and safety. METHODS: Two groups of consecutive patients
      who underwent laparoscopic gastric bypass surgery were selected: 20 OLB patients
      and 61 RYGBP patients. Patients were matched for age, gender, and initial body
      mass index (BMI). Data concerning weight loss, metabolic outcomes, and
      complications were collected prospectively. RESULTS: Mean duration of the
      surgical procedure was shorter in the OLB group (105 vs. 152 min in the RYGBP
      group; p < 0.001). Mean excess BMI loss percent (EBL%) at 6 months and at 1 year
      was greater in the OLB group (76.3 vs. 60.0%, p = 0.001, and 89.0 vs. 71.0%, p =
      0.002, respectively). After adjustment for age, sex, initial BMI, and history of
      previous bariatric surgery, the OLB procedure was still associated with a
      significantly greater 1-year EBL%. Diabetes improvement at 6 months was similar
      between both groups. The early and late complication rates were not statistically
      different. There were three anastomotic ulcers in the OLB group, in smokers, over
      60 years old, who were not taking proton pump inhibitor medication. CONCLUSIONS:
      In this short-term study, we observed a greater weight loss with OLB and similar
      efficiency on metabolic control compared to RYGBP. Long-term evaluation is
      necessary to confirm these outcomes.

PMID- 24442422
TI  - Comparison of gastric fundus invagination and gastric greater curvature plication
      for weight loss in a rat model of diet-induced obesity.
AB  - BACKGROUND: Gastric fundus invagination (GFI) is a novel weight loss procedure.
      The gastric fundus is invaginated inside the gastric lumen and anastomosed to the
      gastric antrum. In gastric plication (GP), the greater curvature is plicated
      inside the gastric lumen leaving a narrow gastric channel for food passage. This
      study compares GFI to GP in a diet-induced obesity rat model. METHODS: Twenty
      Long-Evans male rats were fed a 60% high fat diet for 6 weeks. At 14 weeks of
      age, the rats underwent either GFI (N = 10) or GP (N = 10) surgery. Body weight
      and food intake were measured for 6 weeks. Serum adipokines and ghrelin hormone
      were assayed. Six weeks after surgery, all rats were euthanized and the stomachs
      examined. The two-sample t test was used to compare the results between the two
      groups. RESULTS: All GFI rats had an intact fundus invagination at 6 weeks
      following surgery. The greater curvature plication unfurled in three out of ten
      GP rats. Part of the fundus herniated through the plication suture line in one GP
      rat. There was no significant difference between the mean percent weight change
      for the GFI (4.2 +/- 4.1%) and GP (8.8 +/- 6.0%) groups. There was no difference
      in food intake between both groups. GFI was associated with a significant lower
      fasting ghrelin levels (101.1 +/- 13.1 versus 137.3 +/- 27.4; p = 0.044) compared
      with GP. CONCLUSIONS: GFI offers a more effective and more durable surgical
      alternative for weight loss than GP.

PMID- 24442423
TI  - Predictors of weight loss at 1 year after laparoscopic adjustable gastric banding
      and the role of presurgical quality of life.
AB  - BACKGROUND: There is uncertainty regarding preoperative predictors of a
      successful outcome for bariatric surgery (BarSurg), on which to determine
      appropriateness for such a procedure. Our aims were to identify preoperative
      clinical and psychosocial predictors of success following BarSurg and to explore
      the influence of body mass index (BMI) on these parameters. METHODS: Preoperative
      data, including Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scores
      transformed to Health-Related Quality of Life (HRQOL) scores, were accrued from
      76 morbidly obese adults awaiting BarSurg. Pre- and postoperative data were also
      accrued for 26 patients who had completed 1-year follow-up post-bariatric surgery
      (laparoscopic adjustable gastric banding-LAGB). Statistical analysis was
      performed to assess the relationships between preoperative HRQOL scores,
      preoperative BMI and excess weight loss 1 year following BarSurg (EWL-1 year).
      RESULTS: Preoperative BMI showed a significant independent, negative linear
      correlation with the public distress domain of preoperative quality of life (QOL)
      (r = -0.368, p = 0.001; beta = -0.245, p = 0.009). Preoperative BMI had a
      significant, positive and independent association with EWL-1 year (r = 0.499, p =
      0.009; beta = 0.679, p = 0.015). Preoperative QOL scores had no association with
      EWL-1 year. CONCLUSIONS: Preoperative BMI appears to predict EWL-1 year following
      restrictive bariatric surgery (LAGB). Preoperatively, patients with higher BMI
      appear to manifest greater public distress. Preoperative QOL scores, however, do
      not appear to have any predictive value for EWL-1 year post-LAGB. Preoperative
      BMI should therefore be employed as a predictor of EWL-1 year post-LAGB. Other
      measures of successful outcomes of bariatric surgeries (such as effects on QOL
      scores at 1 year) should be explored in future, larger and longer term studies.

PMID- 24442424
TI  - Resolution of diabetes after bariatric surgery among predominantly African
      American patients: race has no effect in remission of diabetes after bariatric
      surgery.
AB  - BACKGROUND: The aim of this study was to assess the relative efficacy in diabetes
      remission among predominantly African-American patients who have undergone one of
      the three different types of bariatric surgical procedures. METHODS: A total of
      597 morbidly obese patients underwent one of the three bariatric surgical
      procedures at Harper University Hospital, Detroit, Michigan from 2008 to 2011. Of
      the three procedures, 203 (34%) patients had laparoscopic sleeve gastrectomy, 264
      (44.2%) patients had laparoscopic gastric bypass, and 130 (21.8%) had
      laparoscopic adjustable gastric banding. The prevalence of diabetes prior to
      surgery was 20.7, 17.4, and 24%, respectively. There was no statistical
      difference in the prevalence of diabetes among the three surgical groups.
      RESULTS: Of the 119 patients with diabetes, 46 (38.7%) were males and 73 (61.3%)
      were females. The majority of patients were African-Americans (65%). The average
      age of patients was 42.2 +/- 8.3 years for sleeve gastrectomy, 44.8 +/- 7.9 years
      for gastric banding, and 41.5 +/- 7.7 years for gastric bypass surgery. Of all
      the study patients with a preoperative diagnosis of type 2 diabetes, 86 patients
      (72.3%) had resolution of diabetes 1 year after surgery. The resolution of
      diabetes was reported in 89.1, 66.7, and 54.8% of patients who underwent
      laparoscopic gastric bypass, sleeve gastrectomy, and gastric banding,
      respectively. CONCLUSIONS: This study, which was conducted among predominantly
      African-Americans, showed consistent results with other studies. Patients who
      underwent laparoscopic gastric bypass appeared to benefit the most in terms of
      achieving better remission of diabetes.

PMID- 24442425
TI  - Nutritional intake and status in persons with alcohol dependency: data from an
      outpatient treatment programme.
AB  - PURPOSE: Malnutrition increases the risk of developing alcohol-related
      complications. The aim of this study was to describe nutrient intake, nutritional
      status and nutrition-related complications in a Danish population of outpatients
      with alcohol dependency. METHODS: This was a cross-sectional study with a 6-month
      follow-up enrolling persons with alcohol dependency (n = 80) admitted to a
      hospital-based outpatient clinic. Body mass index, the waist-to-hip ratio and
      handgrip strength (HGS) were measured, a 7-day food diary was collected, and
      biochemical testing was conducted. Dual-energy X-ray absorptiometry was performed
      to determine body composition and bone mineral density (BMD). RESULTS: In total,
      64% of the patients with alcohol dependency had vitamin D insufficiency (25-OH
      vit D <50 nmol/l). Compared with surveys of the general population, the patients
      with alcohol dependency had lower energy intake (p = 0.008), s-zinc levels (p <
      0.001), s-magnesium levels (p = 0.02), Z-scores for BMD (lumbar spine, p = 0.03;
      total hip, p = 0.009) and HGS (p < 0.001). Osteopenia was observed in 52% of
      individuals, and overt osteoporosis was noted in 7%. Comparing baseline data with
      data from the follow-up (n = 30), we found a decrease in s-CRP (p = 0.002) and s
      alanine amino transferase (p = 0.01) levels and an increase in s-parathyroid
      hormone levels (p = 0.02). CONCLUSIONS: Patients with alcohol dependency have an
      altered nutritional status and risk of complications, as evidenced by
      osteopenia/osteoporosis and reduced muscle strength. Treatment at an outpatient
      clinic improved the variables related to liver function, but no change was
      observed in nutritional status over time. These findings suggest that specific
      screening and targeted treatment regimens for nutritional deficits could be
      beneficial.

PMID- 24442426
TI  - Prognostic value of serum vascular endothelial growth factor receptor 2 response
      in patients with hepatocellular carcinoma undergoing transarterial
      chemoembolization.
AB  - We aimed to elucidate whether serum VEGFR2 concentration before and after
      transarterial chemoembolization (TACE) can predict survival in patients with
      unresectable hepatocellular carcinoma (HCC). Serum VEGFR2 concentrations were
      serially measured in 169 patients with advanced HCC before and after TACE. We
      defined a decrease in the serum VEGFR2 level>10% from the pretreatment level as
      response. Serum VEGFR2 concentrations decreased in 44 (26.0%) patients at week 4.
      Patients who had a VEGFR2 response at week 4 had a longer median survival than
      those who did not have a VEGFR2 decrease (19.0 vs. 9.8 months, p<0.001). Clinical
      variables associated with OS in addition to VEGFR2 response also included
      extrahepatic metastases (p=0.005) and vascular invasion (p=0.035). VEGFR2
      decrease after TACE (p=0.012) and presence of extrahepatic metastases (p=0.02)
      were independently associated with OS by multivariate analysis. A serum VEGFR2
      concentration decrease at 4 weeks after TACE may predict favorable overall
      survival in patients with advanced HCC.

PMID- 24442427
TI  - Alpha- and beta-cell abnormalities in haemoglobin A1c-defined prediabetes and
      type 2 diabetes.
AB  - New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose
      prediabetes and type 2 diabetes have changed the constitution of the two
      populations. We aimed to investigate the pathophysiological characteristics of
      individuals with HbA1c-defined prediabetes and type 2 diabetes, respectively. Ten
      subjects with HbA1c-defined prediabetes, i.e. HbA1c from 5.7 to 6.4 % (39-46
      mmol/mol), eight newly diagnosed patients with HbA1c-defined type 2 diabetes
      [HbA1c >=6.5 % (>=48 mmol/mol)], and ten controls with HbA1c lower than 5.7 %
      (<39 mmol/mol), were studied. Blood was sampled over 4 h on two separate days
      after a 75 g-oral glucose tolerance test and an isoglycaemic intravenous glucose
      infusion, respectively. Blood was analysed for glucose, insulin, C-peptide,
      glucagon, and incretin hormones. Insulinogenic index, disposition index, glucagon
      suppression, and incretin effect were evaluated. Subjects with HbA1c-defined
      prediabetes showed significantly lower insulinogenic index (P = 0.02),
      disposition index (P = 0.001), and glucagon suppression compared with controls;
      and similar (P = NS) insulinogenic index and glucagon suppression and higher
      disposition index (P = 0.02) compared to HbA1c-diagnosed type 2 diabetic
      patients. The patients with type 2 diabetes showed lower insulinogenic index (P =
      0.0003), disposition index (P < 0.0001), and glucagon suppression compared with
      the controls. The incretin effect was significantly (P < 0.05) reduced in
      patients with HbA1c-defined type 2 diabetes compared to subjects with HbA1c
      defined prediabetes and controls. Plasma levels of incretin hormones were similar
      across the three groups. HbA1c associated negatively with insulinogenic index,
      disposition index, and incretin effect. Our findings show clear alpha- and beta
      cell dysfunction in HbA1c-defined type 2 diabetes compatible with the previously
      described pathophysiology of plasma glucose-defined type 2 diabetes. Furthermore,
      in HbA1c-defined prediabetes, we show defective insulin response in combination
      with inappropriate suppression of glucagon, which may constitute new targets for
      pharmacological interventions. 

PMID- 24442428
TI  - Gr1+ cells suppress T-dependent antibody responses in (NZB x NZW)F1 male mice
      through inhibition of T follicular helper cells and germinal center formation.
AB  - Systemic lupus erythematosus is an autoimmune disease characterized by elevated
      production of autoreactive Abs. The disease has a much higher prevalence in women
      than in men. Although testosterone has been shown to be protective in the
      disease, and estrogens exacerbating, the discrepancy in prevalence between men
      and women is still not well understood and the mechanism behind it is unknown. We
      have recently described that male (New Zealand black [NZB] * New Zealand white
      [NZW])F1 mice have higher levels of Gr1(+)CD11b(+) cells, and that these cells
      suppress autoantibody production in vivo. In this article, we extend our findings
      to show that similarly to humans, female lupus-prone (NZB * NZW)F1 mice also
      respond with stronger Ab responses to thymus-dependent Ag immunization than male
      littermates. Furthermore, the presence or absence of Gr1-expressing cells not
      only control Ag-specific Ab responses in male, but not female, (NZB * NZW)F1
      mice, but also significantly alter the activation and differentiation of CD4(+) T
      cells in vitro and in vivo. In particular, we found that Gr1(+) cells from male
      (NZB * NZW)F1 mice suppress the differentiation and effector function of
      CXCR5(+)PD-1(+) T follicular helper cells, thereby controlling germinal center
      formation and plasma cell differentiation. This new finding strongly supports
      efforts to develop new drugs that target myeloid cell subsets in a number of T
      and B cell-mediated diseases with a female predominance. 

PMID- 24442429
TI  - Induction of endotoxin tolerance by pathogenic Neisseria is correlated with the
      inflammatory potential of lipooligosaccharides and regulated by microRNA-146a.
AB  - In this article, we report that retreatment of human monocytic THP-1 cells and
      primary monocytes with pathogenic Neisseria or with purified lipooligosaccharides
      (LOS) after previous exposure to LOS induced immune tolerance, as evidenced by
      reduced TNF-alpha and IL-1beta cytokine expression. LOS that we have previously
      shown to vary in their potential to activate TLR4 signaling, which was correlated
      with differences in levels of lipid A phosphorylation, had similarly variable
      ability to induce tolerance. Efficacy for induction of tolerance was proportional
      to the level of lipid A phosphorylation, as LOS from meningococcal strain 89I
      with the highest degree of phosphorylation was the most tolerogenic following
      retreatment with LOS or whole bacteria, compared with LOS from gonococcal strains
      1291 and GC56 with reduced levels of phosphorylation. Hydrogen fluoride treatment
      of 89I LOS to remove phosphates rendered the LOS nontolerogenic. Tolerance
      induced by the more highly inflammatory meningococcal LOS was correlated with
      significantly greater downregulation of p38 activation, greater induction of the
      expression of A20 and of microRNA-146a, and greater reductions in IL-1R
      associated kinase 1 and TRAF6 levels following LOS retreatment of cells. The role
      of miR-146a in regulation of induction of TNF-alpha was confirmed by transfecting
      cells with an inhibitor and a mimic of miR-146a. Our results provide a
      mechanistic framework for understanding the variable pathophysiology of
      meningococcal and gonococcal infections given that after an initial exposure,
      greater upregulation of microRNA-146a by more highly inflammatory LOS conversely
      leads to the suppression of immune responses, which would be expected to
      facilitate bacterial survival and dissemination. 

PMID- 24442431
TI  - A genetic defect in mice that impairs missing self recognition despite evidence
      for normal maturation and MHC class I-dependent education of NK cells.
AB  - In studies of a CD1d1-deficient mouse strain, we unexpectedly observed a severely
      impaired capacity for NK cell-mediated rejection of MHC class I-deficient (spleen
      or tumor) cells. Studies of another CD1-defective strain, as well as intercrosses
      with C57BL/6 mice, indicated that the impaired missing self rejection (IMSR) NK
      cell defect was a recessive trait, independent from the targeted CD1 locus.
      Studies with mixed bone marrow chimeras indicated that the defect is intrinsic to
      NK cells. The IMSR mice had normal proportions of NK cells, displaying a typical
      cell surface phenotype, as evaluated using a panel of Abs to developmental
      markers and known receptors. The impaired missing self recognition could not be
      overcome through cytokine stimulation. There was also an impaired capacity with
      respect to NKG2D-dependent cytotoxicity, whereas the mice exhibited normal
      Ly49D/DAP12-dependent responses in vivo and in vitro. The NK cell system of IMSR
      mice showed two hallmarks of MHC-dependent education: skewing of the Ly49
      receptor repertoire and differential in vitro responsiveness between NK cells
      with and without inhibitory receptors for self-MHC ("licensing"). We conclude
      that these mice have a recessive trait that perturbs the missing self reaction,
      as well as NKG2D-dependent responses, whereas other aspects of the NK system,
      such as development, capacity to sense MHC molecules during education, and
      Ly49D/DAP12-dependent responses, are largely intact. 

PMID- 24442430
TI  - CD19 and CD32b differentially regulate human B cell responsiveness.
AB  - B cell activation is regulated by a variety of signals. CD19 positively regulates
      B cell activation, augmenting signals delivered through the BCR complex. In
      contrast, CD32b contains an ITIM and negatively regulates BCR signaling.
      Importantly, there are drugs currently in clinical trials and preclinical
      development that cross-link CD32b to molecules within the BCR complex. We wanted
      to address how single engagement versus cotargeting these molecules affects human
      B cell function. When B cells from healthy individuals were activated by signals
      that mimic a T cell response (IL-21 costimulation), ligation of CD32b, but not
      CD19, inhibited B cell expansion and plasma cell (PC) differentiation. In
      contrast, when B cells were activated through TLR, anti-CD19, but not anti-CD32b,
      blunted the response. However, when both CD19 and CD32b were coengaged by a
      bispecific anti-CD19*CD32b Ab, both types of stimuli were potently inhibited.
      Cross-linking CD19 with CD32b also inhibited Ab-independent functions of B cells,
      such as HLA upregulation, cytokine production, and the ability of B cells to
      prime CD4(+) T cells. Finally, although cross-linking CD19 and CD32b inhibited PC
      differentiation of primary B cells, it did not alter Ig production from pre
      established PCs. These data elucidate the mechanism by which a complex set of
      signals determines the fate of B cell responsiveness. Although signals through
      CD19 influence TLR-driven activation, CD32b impacts the magnitude of the response
      following IL-21 costimulation. Therefore, simultaneous targeting of multiple
      surface molecules may be a necessary approach to comprehensively modulate B cell
      activation in vivo. 

PMID- 24442432
TI  - Human cytomegalovirus infection promotes rapid maturation of NK cells expressing
      activating killer Ig-like receptor in patients transplanted with NKG2C-/-
      umbilical cord blood.
AB  - NK cells are the first lymphoid population recovering after allogeneic
      hematopoietic stem cell transplantation and play a crucial role in early immunity
      after the graft. Recently, it has been shown that human CMV (HCMV)
      infection/reactivation can deeply influence NK cell reconstitution after
      umbilical cord blood transplantation by accelerating the differentiation of
      mature NKG2A(-) killer Ig-like receptor (KIR)(+) NK cells characterized by the
      expression of the NKG2C-activating receptor. In view of the hypothesis that NKG2C
      could be directly involved in NK cell maturation driven by HCMV infection, we
      analyzed the maturation and function of NK cells developing in three patients
      with hematological malignancies given umbilical cord blood transplantation from
      donors carrying a homozygous deletion of the NKG2C gene. We show that HCMV
      infection can drive rapid NK maturation, characterized by the expansion of
      CD56(dim)NKG2A(-)KIR(+) cells, even in the absence of NKG2C expression.
      Interestingly, this expanded mature NK cell subset expressed surface-activating
      KIR that could trigger NK cell cytotoxicity, degranulation, and IFN-gamma
      release. Given the absence of NKG2C, it is conceivable that activating KIRs may
      play a role in the HCMV-driven NK cell maturation and that NK cells expressing
      activating KIRs might contribute, at least in part, to the control of infections
      after transplantation.

PMID- 24442433
TI  - Casein kinase 1gamma1 inhibits the RIG-I/TLR signaling pathway through
      phosphorylating p65 and promoting its degradation.
AB  - The casein kinase 1 (CK1) plays an important role in various biological processes
      by phosphorylating its target proteins. In this study, we demonstrate that
      CK1gamma1 inhibits RNA virus-mediated activation of retinoic acid-inducible gene
      I (RIG-I) signaling by affecting the stability of NF-kappaB subunit p65. First,
      we found that ectopic expression of CK1gamma1 inhibits RIG-I pathway-mediated
      activation of IFN-beta, whereas knockdown of CK1gamma1 potentiates the activation
      of IFN-beta and NF-kappaB induced by Sendai virus (SeV). We then revealed that
      CK1gamma1 interacts with p65 and specifically enhances its phosphorylation at
      Ser(536) induced by SeV. By using an in vitro kinase assay, we confirmed that
      CK1gamma1 can phosphorylate p65 at Ser(536). We also showed that the kinase dead
      mutants CK1gamma1K73A and CK1gamma1N169A did not inhibit SeV-induced activation
      of IFN-beta and NF-kappaB, suggesting that the kinase activity of CK1gamma1 is
      critical for its inhibitory effect on RIG-I signaling. Additionally, we found
      that CK1gamma1 also has the similar effect on TLR signaling. Further analysis
      indicated that CK1gamma1 phosphorylates p65 and consequently promotes its
      degradation by ubiquitin E3 ligases CUL2 and COMMD1. These results revealed a
      novel negative regulatory manner of CK1gamma1 on innate immune signaling. 

PMID- 24442434
TI  - NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous
      colitis.
AB  - NFIL3 is a transcription factor that regulates multiple immunologic functions. In
      myeloid cells, NFIL3 is IL-10 inducible and has a key role as a repressor of IL
      12p40 transcription. NFIL3 is a susceptibility gene for the human inflammatory
      bowel diseases. In this article, we describe spontaneous colitis in Nfil3(-/-)
      mice. Mice lacking both Nfil3 and Il10 had severe early-onset colitis, suggesting
      that NFIL3 and IL-10 independently regulate mucosal homeostasis. Lymphocytes were
      necessary for colitis, because Nfil3/Rag1 double-knockout mice were protected
      from disease. However, Nfil3/Rag1 double-knockout mice adoptively transferred
      with wild-type CD4(+) T cells developed severe colitis compared with Rag1(-/-)
      recipients, suggesting that colitis was linked to defects in innate immune cells.
      Colitis was abrogated in Nfil3/Il12b double-deficient mice, identifying Il12b
      dysregulation as a central pathogenic event. Finally, germ-free Nfil3(-/-) mice
      do not develop colonic inflammation. Thus, NFIL3 is a microbiota-dependent, IL-10
      independent regulator of mucosal homeostasis via IL-12p40. 

PMID- 24442435
TI  - Cleavage of the T cell protein tyrosine phosphatase by the hepatitis C virus
      nonstructural 3/4A protease induces a Th1 to Th2 shift reversible by ribavirin
      therapy.
AB  - Ribavirin has proven to be a key component of hepatitis C therapies both
      involving IFNs and new direct-acting antivirals. The hepatitis C virus-mediated
      interference with intrahepatic immunity by cleavage of mitochondrial antiviral
      signaling protein (MAVS) and T cell protein tyrosine phosphatase (TCPTP) suggests
      an avenue for compounds that may counteract these effects. We therefore studied
      the effects of ribavirin, with or without inhibition of the nonstructural
      (NS)3/4A protease, on intrahepatic immunity. The intrahepatic immunity of wild
      type and NS3/4A-transgenic mice was determined by Western blot, ELISA, flow
      cytometry, and survival analysis. Various MAVS or TCPTP constructs were injected
      hydrodynamically to study their relevance. Ribavirin pretreatment was performed
      in mice expressing a functional or inhibited NS3/4A protease to analyze its
      effect on NS3/4A-mediated changes. Intrahepatic NS3/4A expression made mice
      resistant to TNF-alpha-induced liver damage and caused an alteration of the
      intrahepatic cytokine (IFN-gamma and IL-10) and chemokine (CCL3, CCL17, CCL22,
      CXCL9, and CXCL11) profiles toward an anti-inflammatory state. Consistent with
      this, the number of intrahepatic Th1 cells and IFN-gamma(+) T cells in NS3/4A
      transgenic mice decreased, whereas the amount of Th2 cells increased. These
      effects could be reversed by injection of uncleavable TCPTP but not uncleavable
      MAVS and were absent in a mouse expressing a nonfunctional NS3/4A protease.
      Importantly, the NS3/4A-mediated effects were reversed by ribavirin treatment.
      Thus, cleavage of TCPTP by NS3/4A induces a shift of the intrahepatic immune
      response toward a nonantiviral Th2-dominated immunity. These effects are reversed
      by ribavirin, supporting that ribavirin complements the effects of direct-acting
      antivirals as an immunomodulatory compound. 

PMID- 24442436
TI  - CXCL1 but not IL-6 is required for recurrent herpetic stromal keratitis.
AB  - Herpetic stromal keratitis (HSK) is characterized by an inflammatory response
      that includes neutrophils, macrophages, NK cells, and T cells. The factors that
      are responsible for this inflammation are proinflammatory cytokines and
      chemokines. Many of these factors have been defined for primary disease, but
      relatively few have been investigated during recurrent HSK. The present study was
      designed to determine the role that two of these factors, IL-6 and CXCL1, play
      during recurrent HSK. Results clearly indicate that unlike primary disease, IL-6
      plays no role in recurrent HSK. However, the presence of CXCL1 is required for
      recurrent HSK as evidenced by the lack of corneal disease in mice treated with
      anti-CXCL1 Ab. This was confirmed using mice lacking the primary receptor for
      CXCL1, CXCR2. Corneal disease in this strain was significantly reduced compared
      with wild-type C57BL/6 controls. Unexpectedly, lack of disease occurs even though
      CXCL1 knockout mice display increased viral shedding at the cornea. The primary
      mechanism that CXCL1 plays during disease is its ability to stimulate neutrophils
      to infiltrate the cornea following reactivation. This paper provides further
      evidence that primary HSK and recurrent HSK possess overlapping yet distinct
      disease mechanisms. 

PMID- 24442438
TI  - Anti-CD79 antibody induces B cell anergy that protects against autoimmunity.
AB  - B cells play a major role in the pathogenesis of many autoimmune disorders,
      including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis,
      and type I diabetes mellitus, as indicated by the efficacy of B cell-targeted
      therapies in these diseases. Therapeutic effects of the most commonly used B cell
      targeted therapy, anti-CD20 mAb, are contingent upon long-term depletion of
      peripheral B cells. In this article, we describe an alternative approach
      involving the targeting of CD79, the transducer subunit of the B cell AgR. Unlike
      anti-CD20 mAbs, the protective effects of CD79-targeted mAbs do not require cell
      depletion; rather, they act by inducing an anergic-like state. Thus, we describe
      a novel B cell-targeted approach predicated on the induction of B cell anergy. 

PMID- 24442437
TI  - Flagellin induces antibody responses through a TLR5- and inflammasome-independent
      pathway.
AB  - Flagellin is a potent immunogen that activates the innate immune system via TLR5
      and Naip5/6, and generates strong T and B cell responses. The adaptor protein
      MyD88 is critical for signaling by TLR5, as well as IL-1Rs and IL-18Rs, major
      downstream mediators of the Naip5/6 Nlrc4-inflammasome. In this study, we define
      roles of known flagellin receptors and MyD88 in Ab responses generated toward
      flagellin. We used mice genetically deficient in flagellin recognition pathways
      to characterize innate immune components that regulate isotype-specific Ab
      responses. Using purified flagellin from Salmonella, we dissected the
      contribution of innate flagellin recognition pathways to promote Ab responses
      toward flagellin and coadministered OVA in C57BL/6 mice. We demonstrate IgG2c
      responses toward flagellin were TLR5 and inflammasome dependent; IgG1 was the
      dominant isotype and partially TLR5 and inflammasome dependent. Our data indicate
      a substantial flagellin-specific IgG1 response was induced through a TLR5-,
      inflammasome-, and MyD88-independent pathway. IgA anti-FliC responses were TLR5
      and MyD88 dependent and caspase-1 independent. Unlike C57BL/6 mice, flagellin
      immunized A/J mice induced codominant IgG1 and IgG2a responses. Furthermore,
      MyD88-independent, flagellin-induced Ab responses were even more pronounced in
      A/J MyD88(-/-) mice, and IgA anti-FliC responses were suppressed by MyD88.
      Flagellin also worked as an adjuvant toward coadministered OVA, but it only
      promoted IgG1 anti-OVA responses. Our results demonstrate that a novel pathway
      for flagellin recognition contributes to Ab production. Characterization of this
      pathway will be useful for understanding immunity to flagellin and the rationale
      design of flagellin-based vaccines. 

PMID- 24442439
TI  - Conventional NK cells can produce IL-22 and promote host defense in Klebsiella
      pneumoniae pneumonia.
AB  - It was reported that host defense against pulmonary Klebsiella pneumoniae
      infection requires IL-22, which was proposed to be of T cell origin. Supporting a
      role for IL-22, we found that Il22(-/-) mice had decreased survival compared with
      wild-type mice after intratracheal infection with K. pneumoniae. Surprisingly,
      however, Rag2(-/-) mice did not differ from wild-type mice in survival or levels
      of IL-22 in the lungs postinfection with K. pneumoniae. In contrast, K.
      pneumoniae-infected Rag2(-/-)Il2rg(-/-) mice failed to produce IL-22. These data
      suggested a possible role for NK cells or other innate lymphoid cells in host
      defense and production of IL-22. Unlike NK cell-like innate lymphoid cells that
      produce IL-22 and display a surface phenotype of NK1.1(-)NKp46(+)CCR6(+), lung NK
      cells showed the conventional phenotype, NK1.1(+)NKp46(+)CCR6(-). Mice depleted
      of NK cells using anti-asialo GM1 showed decreased survival and higher lung
      bacterial counts, as well as increased dissemination of K. pneumoniae to blood
      and liver, compared with control-treated mice. NK cell depletion also led to
      decreased production of IL-22 in the lung. Within 1 d postinfection, although
      there was no increase in the number of lung NK cells, a subset of lung NK cells
      became competent to produce IL-22, and such cells were found in both wild-type
      and Rag2(-/-) mice. Our data suggest that, during pulmonary infection of mice
      with K. pneumoniae, conventional NK cells are required for optimal host defense,
      which includes the production of IL-22. 

PMID- 24442440
TI  - PC3-secreted microprotein is a novel chemoattractant protein and functions as a
      high-affinity ligand for CC chemokine receptor 2.
AB  - PC3-secreted microprotein (PSMP) or microseminoprotein is a newly discovered
      secreted protein whose function is currently unknown. In this study, PSMP was
      found to possess chemotactic ability toward monocytes and lymphocytes, and its
      functional receptor was identified as CCR2B. PSMP was identified as a
      chemoattractant protein from a PBMC chemoattractant platform screen that we
      established. The mature secreted PSMP was able to chemoattract human peripheral
      blood monocytes, PBLs, and CCR2B-expressing THP-1 cells, but not peripheral blood
      neutrophils, even though it does not contain the classical structure of
      chemokines. CCR2B was identified as one receptor for PSMP-mediated chemotaxis by
      screening HEK293 cells that transiently expressed classical chemokine receptors;
      results obtained from the chemotaxis, calcium flux, receptor internalization, and
      radioligand-binding assays all confirmed this finding. To further identify the
      major function of PSMP, we analyzed its expression profile in tissues. PSMP is
      highly expressed in benign prostatic hyperplasia and in some prostate cancers,
      and can also be detected in breast tumor tissue. In response to PSMP stimulation,
      phosphorylated ERK levels downstream of CCR2B signaling were upregulated in the
      PC3 cell line. Taken together, our data collectively suggest that PSMP is a
      chemoattractant protein acting as a novel CCR2 ligand that may influence
      inflammation and cancer development. 

PMID- 24442442
TI  - Cutting edge: FYCO1 recruitment to dectin-1 phagosomes is accelerated by light
      chain 3 protein and regulates phagosome maturation and reactive oxygen
      production.
AB  - L chain 3 (LC3)-associated phagocytosis is a process in which LC3, a protein
      canonically involved in engulfing intracellular materials (autophagy), is
      recruited to traditional phagosomes during internalization of extracellular
      payloads. LC3's association with phagosomes has been implicated in regulating
      microbial killing, Ag processing, and phagosome maturation; however, the
      mechanism by which LC3 influences these processes has not been clear. In this
      study, we report that FYVE and coiled-coil domain containing 1 (FYCO1), a protein
      previously implicated in autophagosome trafficking, is recruited directly by LC3
      to Dectin-1 phagosomes. During LC3-associated phagocytosis, FYCO1 recruitment
      facilitates maturation of early p40phox(+) phagosomes into late LAMP1(+)
      phagosomes. When FYCO1 is lacking, phagosomes stay p40phox(+) longer and produce
      more reactive oxygen. 

PMID- 24442441
TI  - Role of neutrophils in IL-17-dependent immunity to mucosal candidiasis.
AB  - Oropharyngeal candidiasis (OPC), caused by the commensal fungus Candida albicans,
      is an opportunistic infection associated with infancy, AIDS, and IL-17-related
      primary immunodeficiencies. The Th17-associated cytokines IL-23 and IL-17 are
      crucial for immunity to OPC, but the mechanisms by which they mediate immunity
      are poorly defined. IL-17RA-deficient humans and mice are strongly susceptible to
      OPC, with reduced levels of CXC chemokines and concomitantly impaired neutrophil
      recruitment to the oral mucosa. Paradoxically, humans with isolated neutropenia
      are typically not susceptible to candidiasis. To determine whether immunity to
      OPC is mediated via neutrophil recruitment, mice lacking CXCR2 were subjected to
      OPC and were found to be highly susceptible, although there was no dissemination
      of fungi to peripheral organs. To assess whether the entire neutrophil response
      is IL-17 dependent, IL-17RA(-/-) and IL-23(-/-) mice were administered neutrophil
      depleting Abs and subjected to OPC. These mice displayed increased oral fungal
      burdens compared with IL-17RA(-/-) or IL-23(-/-) mice alone, indicating that
      additional IL-17-independent signals contribute to the neutrophil response. WT
      mice treated with anti-Gr-1 Abs exhibited a robust infiltrate of CD11b(+)Ly
      6G(low)F4/80(-) cells to the oral mucosa but were nonetheless highly susceptible
      to OPC, indicating that this monocytic influx is insufficient for host defense.
      Surprisingly, Ly-6G Ab treatment did not induce the same strong susceptibility to
      OPC in WT mice. Thus, CXCR2(+) and Gr-1(+) neutrophils play a vital role in host
      defense against OPC. Moreover, defects in the IL-23/17 axis cause a potent but
      incomplete deficiency in the neutrophil response to oral candidiasis. 

PMID- 24442443
TI  - Cutting edge: Self-antigen controls the balance between effector and regulatory T
      cells in peripheral tissues.
AB  - Immune homeostasis in peripheral tissues is achieved by maintaining a balance
      between pathogenic effector T cells (Teffs) and protective Foxp3(+) regulatory T
      cells (Tregs). Using a mouse model of an inducible tissue Ag, we demonstrate that
      Ag persistence is a major determinant of the relative frequencies of Teffs and
      Tregs. Encounter of transferred naive CD4(+) T cells with transiently expressed
      tissue Ag leads to generation of cytokine-producing Teffs and peripheral Tregs.
      Persistent expression of Ag, a mimic of self-antigen, leads to functional
      inactivation and loss of the Teffs with preservation of Tregs in the target
      tissue. The inactivation of Teffs by persistent Ag is associated with reduced ERK
      phosphorylation, whereas Tregs show less reduction in ERK phosphorylation and are
      relatively resistant to ERK inhibition. Our studies reveal a crucial role for Ag
      in maintaining appropriate ratios of Ag-specific Teffs to Tregs in tissues. 

PMID- 24442444
TI  - Image quality assessment of ultra low-dose chest CT using sinogram-affirmed
      iterative reconstruction.
AB  - OBJECTIVES: To assess the image quality of ultra-low-dose computed tomography
      (ULDCT) using sinogram-affirmed iterative reconstruction (SAFIRE) compared to
      reduced dose CT (RDCT). METHODS: Eighty-one consecutive patients underwent non
      enhanced ULDCT using 80 kVp and 30 mAs and contrast-enhanced RDCT using automated
      tube potential selection and tube current modulation. CT images were
      reconstructed with SAFIRE. Image noise and subjective image quality of normal
      structures and various pulmonary lesions were assessed. RESULTS: The mean
      effective doses were 0.29 +/- 0.03 and 2.88 +/- 1.11 mSv for ULDCT and RDCT,
      respectively. ULDCT had significantly higher noise (p < 0.001). Image quality of
      five normal structures was diagnostic in 91.1 % of ULDCT and 100 % of RDCT. With
      ULDCT, the frequencies of non-diagnostic image quality were 2.0 (1/50), 4.6
      (13/280), 25.5 (14/55), and 40.0 (8/20)% for BMIs of < 20, 20-25, 25-30, and >30.
      In the assessment of pulmonary lesions, non-diagnostic image quality was observed
      for 11.2 % of all lesions, 60.9 % of decreased attenuation (significantly more
      frequent for upper lung lesions), and 23.5 % of ground-glass nodules. CONCLUSION:
      ULDCT generates diagnostic images in patients with a BMI <=25, but is of limited
      use for lesions with decreased attenuation, ground-glass nodules, or those
      located in the upper lobe. KEY POINTS: * Iterative reconstruction enables ultra
      low-dose CT (ULDCT) with very low radiation doses. * Image quality of ULDCT
      depends on the patient body mass index (BMI). * Selection of kVp and mAs depends
      on both BMI and lesion type. * Diagnosis of pulmonary emphysema or ground-glass
      nodules requires higher radiation doses.

PMID- 24442445
TI  - Reply to Letter to the Editor re: Diagnostic accuracy of digital breast
      tomosynthesis versus digital mammography for benign and malignant lesions in
      breasts: a meta-analysis.

PMID- 24442447
TI  - Single injections of apoA-I acutely improve in vivo glucose tolerance in insulin
      resistant mice.
AB  - AIMS/HYPOTHESIS: Apolipoprotein A-I (apoA-I), the main protein constituent of
      HDL, has a central role in the reverse cholesterol-transport pathway, which
      together with the anti-inflammatory properties of apoA-I/HDL provide
      cardioprotection. Recent findings of direct stimulation of glucose uptake in
      muscle by apoA-I/HDL suggest that altered apoA-I and HDL functionality may be a
      contributing factor to the development of diabetes. We have studied the in vivo
      effects of short treatments with human apoA-I in a high-fat diet fed mouse model.
      In addition to native apoA-I, we investigated the effects of the cardioprotective
      Milano variant (Arg173Cys). METHODS: Male C57Bl6 mice on a high-fat diet for 2
      weeks that received a single injection of human apoA-I proteins (wild-type and
      Milano) were analysed for blood glucose and insulin levels during a 3 h
      incubation followed by glucose tolerance tests. Incorporation of injected human
      apoA-I protein into HDLs was analysed by native gel electrophoresis. RESULTS:
      ApoA-I treatment significantly improved insulin secretion and blood glucose
      clearance in the glucose tolerance test, with an efficiency exceeding that of
      lean control animals, and led to decreased basal glucose during the 3 h
      incubation. Notably, the two apoA-I variants triggered insulin secretion and
      glucose clearance to the same extent. CONCLUSIONS/INTERPRETATION: ApoA-I
      treatment leads to insulin- and non-insulin-dependent effects on glucose
      homeostasis. The experimental model of short-term (2 weeks) feeding of a high-fat
      diet to C57Bl6 mice provides a suitable and time-efficient system to unravel the
      resulting tissue-specific mechanisms of acute apoA-I treatment that lead to
      improved glucose homeostasis.

PMID- 24442446
TI  - Probing the wild-type HRas activation mechanism using steered molecular dynamics,
      understanding the energy barrier and role of water in the activation.
AB  - Ras is one of the most common oncogenes in human cancers. It belongs to a family
      of GTPases that functions as binary conformational switches by timely switching
      of their conformations from GDP to GTP and vice versa. It attains the final
      active state structure via an intermediate GTP-bound state. The transition
      between these states is a millisecond-time-scale event. This makes studying this
      mechanism beyond the scope of classical molecular dynamics. In the present study,
      we describe the activation pathway of the HRas protein complex along the distance
      based reaction coordinate using steered molecular dynamics. Approximately ~720 ns
      of MD simulations using CMD and SMD was performed. We demonstrated the change in
      orientation and arrangement of the two switch regions and the role of various
      hydrogen bonds during the activation process. The weighted histogram analysis
      method was also performed, and the potential of mean force was calculated between
      the inactive and active via the intermediate state (state 1) of HRas. The study
      indicates that water seems to play a crucial role in the activation process and
      to transfer the HRas protein from its intermediate state to the fully active
      state. The implications of our study hereby suggest that the HRas activation
      mechanism is a multistep process. It starts from the inactive state to an
      intermediate state 1 followed by trapping of water molecules and flipping of the
      Thr35 residue to form a fully active state (state 2). This state 2 also comprises
      Gly60, Thr35, GTP, Mg(2+) and water-forming stable interactions.

PMID- 24442449
TI  - Ultrastructure of xylem parenchyma cells of barley roots in relation to ion
      transport to the xylem.
AB  - The structure of xylem parenchyma cells is examined in relation to transport of
      ions through the root. Measurement of uptake of (86)Rb(+) and its transport
      through the root at different distances from the apex show that this is a general
      activity along the length of the root and not confined to a limited region. Thus
      transport through the root is not stopped by removal of that part of the root tip
      containing metaxylem vessels with living contents. The structure of xylem
      parenchyma appears to be suitable for involvement in ion transport from the stele
      to the xylem. At 1 cm behind the tip, where metaxylem vessels have no living
      contents but ion uptake and transport are going on at high rates, xylem
      parenchyma cells are rich in cytoplasm with extensive rough endoplasmic reticulum
      and well-developed mitochondria. Their cell walls contain numerous plasmodesmata,
      establishing the possibility of a symplastic pathway across the stele up to the
      vessels. The results are discussed in relation to regulation of ion transport to
      the xylem vessels in roots. 

PMID- 24442448
TI  - Psychological distress, cardiovascular complications and mortality among people
      with screen-detected type 2 diabetes: follow-up of the ADDITION-Denmark trial.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine the association between
      psychological distress and the risk of cardiovascular disease (CVD) events and
      all-cause mortality in patients with screen-detected type 2 diabetes mellitus. In
      addition, we explored whether or not metabolic control and medication adherence
      could explain part of this association. METHODS: A follow-up study was performed
      including 1,533 patients aged 40-69 years with screen-detected type 2 diabetes
      mellitus identified in general practice during 2001-2006 in the Denmark arm of
      the ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People with
      Screen-Detected Diabetes in Primary Care) study. Mental health was measured at
      baseline with the Mental Health Inventory 5 (MHI-5). Psychological distress was
      defined as an MHI-5 score of <= 68 (18.2% of the population). CVD risk factors
      were measured at baseline and repeated at the follow-up examination. Information
      on death, hospital discharge diagnosis, and antihypertensive and lipid-lowering
      drug treatment was obtained from national registers. Cox proportional regression
      was used to estimate HRs for the association between psychological distress, CVD
      events and all-cause mortality. Age- and sex-adjusted risk difference analyses
      were performed to estimate differences in meeting treatment targets. RESULTS:
      Patients with psychological distress had a 1.8-fold higher mortality rate (HR
      1.76, 95% CI 1.23, 2.53) and a 1.7-fold higher risk of having a CVD event (HR:
      1.69, 95% CI 1.05, 2.70) compared with those with an MHI-5 score of >68. Overall,
      psychological distress was not associated with the ability to meet treatment
      targets for HbA1c levels, cholesterol levels or BP, or to redeem antihypertensive
      or lipid-lowering drug treatment. CONCLUSIONS/INTERPRETATION: In people detected
      and treated early in the diabetes disease trajectory, those with psychological
      distress at the time of diagnosis had a higher risk of CVD events and death than
      those without psychological distress.

PMID- 24442450
TI  - The development of the cuticle in Phormium tenax.
AB  - As seen in the scanning electron microscope the surface wax of leaves of Phormium
      tenax L. consists of vertical, plate-like crystals. These increase in size and
      number and undergo a change in form during development. The abaxial surface has a
      dense covering of wax crystals, but none are present on the ridges over vascular
      tissues. Numerous papillae are found between these ridges in later stages of
      development. On the adaxial surface both wax crystals and papillae are present
      only around infrequent stomata.When viewed in section normal to the leaf surface
      the cuticle is first apparent as a thin, lamellate layer. Another layer
      containing a reticulum of electrondense material increases in thickness beneath
      the lamellae during development. This layer eventually becomes the most extensive
      component of the cuticle. Both the adaxial and abaxial cuticles show a similar
      pattern of development. 

PMID- 24442451
TI  - Sieve-tube proteins from Cucurbita maxima.
AB  - The two main proteins from the phloem exudate of Cucurbita maxima Duchesne have
      been isolated by ammonium-sulfate precipitation, DEAE-cellulose chromatography,
      and gel filtration, and have been characterized. They comprise about 40% each of
      the total protein. The amino-acid composition of these two proteins has been
      determined. Both are highly basic with an IEP above 9.5. The smaller protein has
      a molecular weight of ca. 30000 as determined by analytical ultracentrifugation,
      gel filtration, and SDS polyacrylamide gel electrophoresis. It easily dimerizes
      to a form which appears to be the naturally occurring structure. The larger
      protein has a molecular weight of 116000 (ultracentrifugation, SDS polyacrylamide
      gel electrophoresis). This protein forms a gel in the absence of SH-protecting
      agents. Several minor proteins have been detected by polyacrylamide gel
      electrophoresis. 

PMID- 24442452
TI  - The ultrastructural development of spherosomes and oil bodies in the developing
      embyro of Crambe abyssinica.
AB  - The development of the cotyledon cells of Crambe abyssinica was studied using the
      electron microscope.New evidence is presented, concerning the site of origin of
      the oil body. The spherosomes and oil bodies were found to be separate entities,
      with different sites of origin and function within the cell.The spherosomes,
      which were shown to be present in the cell before the onset of oil body
      formation, and formed from the endoplasmic reticulum, contains acid beta
      glycerophosphatase. At least one of its functions is to supply a hydrolytic
      enzyme to the vacuoles in which the alcurone grains subsequently develop.Oil
      bodies were found to develop from small areas of particulate material in the
      cytoplasm 8-10 days after petal fall, and their function appears to be as sites
      of an oil storage product (triglyceride), which is synthesised during seed
      development.The development of the protein body is also briefly discussed. 

PMID- 24442453
TI  - An excitable membrane in the stalked glands of Drosera capensis L.
AB  - Shortly after feeding the surface of the gland of Drosera capensis L. with whole
      milk or other protein sources the plasmalemma adjacent to the tracheid becomes
      highly modified. No vesicle is seen to approach the membrane from within the
      cytoplasm, but the surface of the membrane grows and evaginates outwards forming
      a small protruding papilla or bleb about 50-100 nm across. Finally the bleb is
      pinched off at the base and disappears into the tracheid.This form of stimulated
      "exocytosis" does not appear to have been observed in any other plant tissue, but
      may be a feature of those specialised organs that take up rapidly large
      quantities of externally applied nutrient. 

PMID- 24442454
TI  - Regulation of organogenesis in small explants of superficial tissue of Nicotiana
      tabacum L.
AB  - Small explants composed of 3-6 layers of epidermal and subepidermal cells excised
      from floral branches of Nicotiana tabacum are capable of de novo organogenesis.
      Continuous mitoses without organogenesis, or mitoses followed by the formation of
      floral buds, vegetative buds or roots can be obtained by varying the auxin
      cytokinin-sucrose ratio in the medium. The physiological stage of the floral
      branches, and light and darkness had also an influence on the de novo
      organogenesis. Best floral-bud formation was obtained when explants were taken
      from plants in which the terminal bud was in the green-fruit stage, and were
      cultured on a medium with indole-3-acetic acid and kinetin both at 10(-6) M and
      with 3% sucrose, in the light. For differentiation of vegetative buds, the
      optimal auxin/cytokinin ratio was one tenth of that for floral-bud formation,
      while the sucrose concentration was the same. Optimal conditions for root
      formation were: explants from plants in which the terminal bud carried a mature
      fruit; 10(-7) M kinetin, 10(-5) M indole-3-butyric acid, and 1% sucrose in the
      medium; and culture in darkness. The optimal medium for callus formation
      contained 5*10(-6)M 2,4-dichlorophenoxyacetic acid, 10(-7) M kinetin and 3%
      sucrose. 

PMID- 24442455
TI  - [Phytochrome control of enzymes involved in flavonoid synthesis in cell
      suspension cultures of parsley (Petroselinum hortense Hoffm.)].
AB  - Enzymes involved in flavonoid synthesis in parsley (Petroselinum nortense Hoffm.)
      cell suspension cultures are induced by light. It has been suggested that the
      regulation of the enzymes of phenylpropanoid metabolism (group 1) is independent
      of that of the enzymes of flavonoid synthesis proper (group 2) [Hahl-brock, K.,
      Ebel, J., Ortmann, R., Sutter, A., Wellmann, E., Grisebach, H.: Biochim. biophys.
      Acta (Amst.) 244, 7-15 (1971)]. Phytochrome was demonstrated to be involved in
      the light effect controlling flavonoid synthesis. Phytochrome is only effective
      after a preceding irradiation with ultraviolet light (lambdamax<300 nm)
      [Wellmann, E.: Planta (Berl.) 101, 283-286 (1971)]. - In order to determine
      whether phytochrome affects phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), a
      group 1 enzyme, or exerts a general effect of all enzymes of the flavonoid
      pathway. PAL and two enzymes from group 2, chalcone-flavanone isomerase and UDP
      apiose synthetase, were investigated. Under appropriate conditions of irradiation
      (low UV-dose with subsequent red/far-red pulses) both group 2 enzymes were shown
      to be controlled by phytochrome to the same extent as PAL. The UV-induced
      increase in activity of all three enzymes is reduced to about 70% by an
      irradiation for 10 min with far-red light. This far-red effect is fully
      reversible by a subsequent irradiation with 10 mith red light. There is no
      evidence for a rate limiting enzyme (or group of enzymes) involved in flavonoid
      formation with respect to phytochrome control. 

PMID- 24442457
TI  - Erratum.

PMID- 24442456
TI  - Cytochalasin-B-induced inhibition of root-hair growth in lettuce seedlings and
      its reversal by benzyladenine.
AB  - Cytochalasin-B (CB) inhibited root-hair growth in lettuce seedlings. This
      inhibition was partially overcome by benzyl-adenine (BA) and kinetin, but not by
      gibberellic acid, indole-3-acetic acid, abscisic acid, cyclic AMP or ethylene.
      BA, however, was unable to prevent the inhibition of cytoplasmic streaming
      induced by CB, a result indicating that cytoplasmic streaming is not necessary
      for root-hair growth. 

PMID- 24442464
TI  - Litigation in residency training programs and suggested due process guidelines
      for "residents in trouble".
AB  - Litigation involving the dismissal of residents has increased in the past
      decades. A review of relevant court decisions and their implications for
      residency training programs is provided. To assure due process in such cases and
      to help programs deal fairly with situations involving problem residents that may
      never come to frank dismissal, a set of guidelines to assist training programs in
      dealing ivith residents "in trouble" is presented. The guidelines were developed
      collaboratively at University of California at Los Angeles (UCLA) and the
      University of Southern California (USC) and were reviewed and approved by the
      local hospital, university, and Veterans Affairs counsels to assure compliance
      with institutional policies and procedures regulating due process for employees
      and students. The guidelines were also reviewed and approved by an American
      Association of Directors of Psychiatric Residency Training (AADPRT) task force,
      but they were never published or widely distributed. Although modifications of
      these guidelines may be required to meet local educational or institutional
      variations, or to meet variations in state law or precedent, these suggestions
      provide a useful template with which to develop adequate and effective due
      process procedures. 

PMID- 24442463
TI  - Effects of exenatide in a morbidly obese patient with type 2 diabetes.
AB  - INTRODUCTION: The effect of exenatide in weight loss has been reported. Presented
      here is a case of a morbidly obese patient with type 2 diabetes using exenatide
      who dramatically lost her body weight in a year and experienced improved glycemic
      control. CASE REPORT: Exenatide therapy was initiated for a 59-year-old morbidly
      obese Japanese woman with type 2 diabetes. To examine the effects of the
      exenatide treatment, continuous glucose monitoring was performed, and blood was
      drawn at 0, 30, 60, 120, and 180 min after breakfast to measure insulin,
      glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic
      peptide (GIP) levels. After 1 year of exenatide therapy, the patient lost 37.5
      kg, her glycemic control improved, and her insulin sensitivity recovered. The
      patient's levels of insulin, glucagon, active GLP-1, and total GIP also decreased
      after 1 year of exenatide treatment. CONCLUSION: The exenatide treatment was
      effective for reducing body weight and improving glycemic control. After 1 year
      of exenatide treatment, decreased glucagon, active GLP-1, and total GIP levels
      were observed following a meal, suggesting that exenatide might affect these
      hormonal reactions.

PMID- 24442465
TI  - Neurological proficiencies for psychiatrists : a pilot survey.
AB  - Faculty at the University of California at Los Angeles were surveyed regarding
      appropriate proficiencies for general and subspecialty trained psychiatrists with
      respect to a number of neurological problems. Survey responses were obtained from
      40 psychiatrists and 7 neurologists, representing 69% and 70%, respectively, of
      those surveyed in each group. Five levels of proficiency were defined, ranging
      from making a screening diagnosis to instituting definitive treatment and having
      laboratory expertise. Psychiatrists' expectations ranged from screening to
      monitoring proficiencies for a wide range of higher cortical func tion
      neurological disorders. Higher expected proficiencies were noted for
      schizophreniform symptoms of epilepsy, acute extrapyramidal reactions, tardive
      dyskinesias, dementias, and depressive syndromes associated with brain damage. 

PMID- 24442466
TI  - Training residents in psychotherapy for psychotic patients : curricular
      constraints and clinical suggestions.
AB  - In recent years, residency programs have neglected to teach psychotherapy for
      psychotic patients to their trainees. This training has value in teaching
      residents how to more fully understand psychopathology, to understand the concept
      of the unconscious, and to work more effectively in using combined
      pharmacopsychotherapy with psychotic patients. The author suggests that an
      "affect-centered" psychotherapy approach is both clinically appropriate and
      educationally useful with psychotic patients. Recommendations for teaching this
      approach are given. 

PMID- 24442467
TI  - Conflict with physician pregnancy revisited.
AB  - A 10-year follow-up survey found medical school physicians (N = 200) at one
      institution were more interested in and accepting of pregnancy among colleagues.
      A greater number of physicians in 1990 than in 1980 reported that pregnant
      colleagues maintained their work efficiency and interest in medicine. Fewer
      physicians in 1990 reported being inconvenienced during a colleague's pregnancy,
      and fewer perceived hiring women of childbearing age to be a risk to the optimal
      functioning of their departments. 

PMID- 24442468
TI  - Student education and recruitment into psychiatry : a synergistic proposal.
AB  - The authors propose that the most effective recruitment strategy is a strong
      psychiatric curriculum positioned as a relevant and integral part of
      undergraduate education for primary care physicians. The necessary ingredients
      are educational leadership by the chair, a multifaceted curriculum, shared
      teaching with generalists, and an emphasis on gender and ethnic minority issues.
      In changing times, it is essential that psychiatric educators remain at the
      center of the educational stage and continue to attract medical students through
      sharing the excitement of the intellectual and clinical challenges in psychiatry.

PMID- 24442469
TI  - Review resident data before computer entry.

PMID- 24442470
TI  - In reply.

PMID- 24442471
TI  - The moral myopia of academia and "the big chill" of managed care.

PMID- 24442472
TI  - In reply.

PMID- 24442473
TI  - Gender differences in career paths in psychiatry : in reply.

PMID- 24442474
TI  - Frequently asked questions about neuropsychiatry.

PMID- 24442476
TI  - Cell-permeable dual inhibitors of protein kinases CK2 and PIM-1: structural
      features and pharmacological potential.
AB  - It has been proposed that dual inhibitors of protein kinases CK2 and PIM-1 are
      tools particularly valuable to induce apoptosis of cancer cells, a property,
      however, implying cell permeability, which is lacking in the case of selective
      CK2/PIM-1 inhibitors developed so far. To fill this gap, we have derivatized the
      scaffold of the promiscuous CK2 inhibitor TBI with a deoxyribose moiety,
      generating TDB, a selective, cell-permeable inhibitor of CK2 and PIM-1. Here, we
      shed light on the structural features underlying the potency and narrow
      selectivity of TDB by exploiting a number of TDB analogs and by solving the 3D
      structure of the TDB/CK2 complex at 1.25 A resolution, one of the highest
      reported so far for this kinase. We also show that the cytotoxic efficacy of TDB
      is almost entirely due to apoptosis, is accompanied by parallel inhibition of
      cellular CK2 and PIM-1, and is superior to both those observed combining
      individual inhibitors of CK2 and PIM-1 and by treating cells with the CK2
      inhibitor CX4945. These data, in conjunction with the observations that cancer
      cells are more susceptible than non-cancer cells to TDB and that such a
      sensitivity is maintained in a multi-drug resistance background, highlight the
      pharmacological potential of this compound.

PMID- 24442479
TI  - Quantitative PET and SPECT performance characteristics of the Albira Trimodal pre
      clinical tomograph.
AB  - The Albira Trimodal pre-clinical scanner comprises PET, SPECT and CT sub-systems
      and thus provides a range of pre-clinical imaging options. The PET component
      consists of three rings of single-crystal LYSO detectors with axial/transverse
      fields-of-view (FOVs) of 148/80 mm. The SPECT component has two opposing CsI
      detectors (100 * 100 mm2) with single-pinhole (SPH) or multi(9)-pinhole (MPH)
      collimators; the detectors rotate in 6 degrees  increments and their spacing can
      be adjusted to provide different FOVs (25 to 120 mm). The CT sub-system provides
      'low' (200 uA, 35 kVp) or 'high' (400 uA, 45 kVp) power x-rays onto a flat-panel
      CsI detector. This study examines the performance characteristics and
      quantitative accuracy of the PET and SPECT components. Using the NEMA NU 4-2008
      specifications (22Na point source), the PET spatial resolution is 1.5 + 0.1 mm on
      axis and sensitivity 6.3% (axial centre) and 4.6% (central 70 mm). The usable
      activity range is <= 10 MBq (18F) over which good linearity (within 5%) is
      obtained for a uniform cylinder spanning the axial FOV; increasing deviation from
      linearity with activity is, however, observed for the NEMA (mouse) line source
      phantom. Image uniformity axially is within 5%. Spatial resolution (SPH/MPH) for
      the minimum SPECT FOV used for mouse imaging (50 mm) is 1.5/1.7 mm and point
      source sensitivity 69/750 cps MBq-1. Axial uniformity of SPECT images (%CV of
      regions-of-interest counts along the axis) is mostly within 8% although there is
      a range of 30-40% for the largest FOV. The variation is significantly smaller
      within the central 40 mm. Instances of count rate nonlinearity (PET) and axial
      non-uniformity (SPECT) were found to be reproducible and thus amenable to
      empirical correction.

PMID- 24442480
TI  - Development and refinement of new statistical methods for enhanced syndromic
      surveillance during the 2012 Olympic and Paralympic Games.
AB  - Prior to the 2012 London Olympic and Paralympic Games, new statistical methods
      had to be developed for the enhanced syndromic surveillance during the Games.
      Different methods were developed depending on whether or not historical data were
      available. Practical solutions were needed to cope with the required daily
      reporting and data quality issues. During the Games, nearly 4800 signals were
      tested on average each day, generating statistical alarms that were assessed to
      provide information on areas of potential public health concern and reassurance
      that no major adverse incident had occurred. GRAPHICAL ABSTRACT:
      spjhi;21/2/159/FIG41460458213517577 F1 fig4-1460458213517577.

PMID- 24442478
TI  - Mitochondria dynamism: of shape, transport and cell migration.
AB  - Mitochondria are highly dynamic and functionally versatile organelles that
      continuously fragment and fuse in response to different physiological needs of
      the cell. The list of proteins that strictly regulate the morphology of these
      organelles is constantly growing, adding new players every day and new pieces to
      the comprehension and elucidation of this complex machinery. The structural
      complexity of mitochondria is only paralled by their functional versatility.
      Indeed, changes in mitochondria shape play critical roles in vertebrate
      development programmed cell death and in various processes of normal cell
      physiology, such as calcium signaling, reactive oxygen species production, and
      lifespan. Here, we present the latest findings on the regulation of mitochondrial
      dynamics and some of their physiological roles, focusing on cell migration. In
      cells where migration represents a crucial function in their physiology, such as
      T and tumoral metastatic cells, mitochondria need to be fragmented and recruited
      to specific subcellular regions to make movement possible. In depth analysis of
      this role of mitochondrial dynamics should help in identifying potential targeted
      therapy against cancer or in improving the immune system's efficiency. 

PMID- 24442477
TI  - Embryonic origins of human vascular smooth muscle cells: implications for in
      vitro modeling and clinical application.
AB  - Vascular smooth muscle cells (SMCs) arise from multiple origins during
      development, raising the possibility that differences in embryological origins
      between SMCs could contribute to site-specific localization of vascular diseases.
      In this review, we first examine the developmental pathways and embryological
      origins of vascular SMCs and then discuss in vitro strategies for deriving SMCs
      from human embryonic stem cells (ESCs) and induced pluripotent stem cells
      (iPSCs). We then review in detail the potential for vascular disease modeling
      using iPSC-derived SMCs and consider the pathological implications of
      heterogeneous embryonic origins. Finally, we touch upon the role of human ESC
      derived SMCs in therapeutic revascularization and the challenges remaining before
      regenerative medicine using ESC- or iPSC-derived cells comes of age. 

PMID- 24442482
TI  - Targeting metabolism with a ketogenic diet during the treatment of glioblastoma
      multiforme.
AB  - Retrospective data suggests that low serum glucose levels during the treatment of
      glioblastoma multiforme (GBM) may improve clinical outcomes. As such, many
      patients are implementing a ketogenic diet (KD) in order to decrease serum
      glucose flux while simultaneously elevating circulating ketones during radiation
      therapy and chemotherapy for the treatment of GBM. With IRB approval, a
      retrospective review of patients with high-grade glioma treated with concurrent
      chemoradiotherapy and adjuvant chemotherapy was carried out from August 2010 to
      April 2013. Serum glucose and ketone levels, dexamethasone dose, and toxicity of
      patients undergoing a KD during treatment were also assessed. Blood glucose
      levels were compared between patients on an unspecified/standard diet and a KD.
      Toxicity was assessed by Common Terminology Criteria for Adverse Events version
      4. In total, 53 patients were analyzed. Six underwent a KD during treatment. The
      diet was well tolerated with no grade III toxicity and one episode of grade II
      fatigue. No episodes of symptomatic hypoglycemia were experienced. Four patients
      are alive at a median follow-up of 14 months. The mean blood glucose of patients
      on a standard diet was 122 versus 84 mg/dl for those on a KD. Based on this
      retrospective study, a KD appears safe and well tolerated during the standard
      treatment of GBM. Dietary restriction of carbohydrates through a KD reduces serum
      glucose levels significantly, even in conjunction with high dose steroids, which
      may affect the response to standard treatment and prognosis. Larger prospective
      trials to confirm this relationship are warranted.

PMID- 24442483
TI  - CXCL12 secreted from glioma stem cells regulates their proliferation.
AB  - Emerging evidence suggests that the chemokine CXCL12 and its receptor CXCR4,
      which are expressed by glioma stem cells (GSCs), play an important role in
      tumorigenesis. To provide evidence for establishing a new therapy targeting the
      CXCL12/CXCR4 pathway, we investigated whether CXCL12 secreted from GSCs
      contributed to their proliferation and promoted angiogenesis in murine GSCs.
      Angiogenetic functions and proliferation of GSCs with or without CXCL12
      inhibitors were evaluated in an in vitro model using tube formation assays, RT
      PCR, and proliferation, as well as in an in vivo syngenic model. In endothelial
      culture, the morphology and gene expression of GSCs changed from stem cell-like
      characteristics to endothelial cell-like features. CXCL12 expression increased in
      endothelial cell-like GSCs. CXCL12 blockage with siRNA or shRNA markedly
      inhibited cell proliferation in vitro. CXCL12 knockdown with shRNA also inhibited
      tumor growth in vivo. On the other hand, CXCL12/CXCR4 blockage affected neither
      tube formation in vitro nor angiogenesis in vivo. The CXCL12 secreted from GSCs
      (autocrine/paracrine CXCL12) regulates their proliferation, but probably not
      angiogenesis.

PMID- 24442484
TI  - Cilengitide treatment of newly diagnosed glioblastoma patients does not alter
      patterns of progression.
AB  - The integrin antagonist cilengitide has been explored as an adjunct with anti
      angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT 
      > TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal
      clinical observations indicate that anti-angiogenic treatment may result in
      altered patterns of tumor progression. Using a standardized approach, we analyzed
      patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of
      cilengitide added to TMZ/RT -> TMZ in newly diagnosed glioblastoma. Thirty
      patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial
      served as a reference. MRIcro software was used to map location and extent of
      initial preoperative and recurrent tumors on MRI of both groups into the same
      stereotaxic space which were then analyzed using an automated tool of image
      analysis. Clinical and outcome data of the cilengitide-treated patients were
      similar to those of the EORTC/NCIC trial except for a higher proportion of
      patients with a methylated O(6)-methylguanyl-DNA-methyltransferase gene promoter.
      Analysis of recurrence pattern revealed neither a difference in the size of the
      recurrent tumor nor in the distance of the recurrences from the preoperative
      tumor location between groups. Overall frequencies of distant recurrences were 20
      % in the reference group and 19 % (4/21 patients) in the cilengitide group.
      Compared with TMZ/RT -> TMZ alone, the addition of cilengitide does not alter
      patterns of progression. This analysis does not support concerns that integrin
      antagonism by cilengitide may induce a more aggressive phenotype at progression,
      but also provides no evidence for an anti-invasive activity of cilengitide in
      patients with newly diagnosed glioblastoma.

PMID- 24442485
TI  - Yersinia pseudotuberculosis infections in goats and other animals diagnosed at
      the California Animal Health and Food Safety Laboratory System: 1990-2012.
AB  - Yersinia pseudotuberculosis is a recognized zoonotic food-borne pathogen;
      however, little is known about the ecology and epidemiology of diseases caused by
      the bacterium in California. The objective of the current study was to contribute
      to the knowledge of the diseases caused by Y. pseudotuberculosis in goats, the
      animal species most frequently reported with clinical yersiniosis to the
      California Animal Health and Food Safety Laboratory System, to better understand
      the epidemiology of this disease. A 23-year retrospective study was conducted to
      characterize the syndromes caused by the bacterium in goats and their
      temporospatial distribution, and to determine the number of cases in other animal
      species. Yersinia pseudotuberculosis-associated disease was diagnosed in 42 goats
      from 21 counties, with a strong seasonality in winter and spring. Most cases
      (88%) were observed within particular years (1999, 2004-2006, 2010-2011). The
      most frequently diagnosed syndrome was enteritis and/or typhlocolitis (64.3%),
      followed by abscessation (14.3%), abortion (11.9%), conjunctivitis (4.75%), and
      hepatitis (4.75%). Among other animal species, 59 cases were diagnosed in non
      poultry avian species and 33 in mammals other than goats. 

PMID- 24442481
TI  - Remote neurodegeneration: multiple actors for one play.
AB  - Remote neurodegeneration significantly influences the clinical outcome in many
      central nervous system (CNS) pathologies, such as stroke, multiple sclerosis, and
      traumatic brain and spinal cord injuries. Because these processes develop days or
      months after injury, they are accompanied by a therapeutic window of opportunity.
      The complexity and clinical significance of remote damage is prompting many
      groups to examine the factors of remote degeneration. This research is providing
      insights into key unanswered questions, opening new avenues for innovative
      neuroprotective therapies. In this review, we evaluate data from various remote
      degeneration models to describe the complexity of the systems that are involved
      and the importance of their interactions in reducing damage and promoting
      recovery after brain lesions. Specifically, we recapitulate the current data on
      remote neuronal degeneration, focusing on molecular and cellular events, as
      studied in stroke and brain and spinal cord injury models. Remote damage is a
      multifactorial phenomenon in which many components become active in specific time
      frames. Days, weeks, or months after injury onset, the interplay between key
      effectors differentially affects neuronal survival and functional outcomes. In
      particular, we discuss apoptosis, inflammation, oxidative damage, and autophagy
      all of which mediate remote degeneration at specific times. We also review
      current findings on the pharmacological manipulation of remote degeneration
      mechanisms in reducing damage and sustaining outcomes. These novel treatments
      differ from those that have been proposed to limit primary lesion site damage,
      representing new perspectives on neuroprotection. 

PMID- 24442486
TI  - Human cytomegalovirus induces upregulation of arginase II: possible implications
      for vasculopathies.
AB  - Both human cytomegalovirus (HCMV) and arginase II (ARG II) have been implicated
      in the pathogenesis of cardiovascular diseases. The effects of HCMV on ARG II are
      unknown. The aim of this study was to investigate the effects of HCMV on ARG II
      expression in endothelial and vascular smooth muscle cells (SMC) both in vitro
      and ex vivo. Endothelial and SMC were infected with either HCMV or UV-irradiated
      HCMV. Expression of ARG II, endothelial or inducible nitric oxide synthase (eNOS
      and iNOS, respectively) and viral immediate early (IE) was quantified using
      quantitative PCR. Ganciclovir and short interfering RNA were used to determine
      the viral gene mediating the effects on ARG II. Detection of viral antigens and
      ARG II expression was performed by immunofluorescence or immunohistochemistry.
      HCMV infection increased both ARG II mRNA and protein levels in the examined
      cells; this effect was mediated by the HCMV IE2-p86 protein. The upregulation of
      ARG II was accompanied by a downregulation of eNOS but an induction of iNOS in
      HCMV-infected endothelial cells. Both eNOS and iNOS expressions were induced in
      HCMV-infected SMC. ARG II was abundantly expressed in endothelial cells, foam
      cells and SMC and was importantly significantly upregulated in HCMV
      immunoreactive human carotid atherosclerotic plaques. HCMV IE2-p86 mediates ARG
      II upregulation in vitro and ARG II is co-expressed with HCMV antigens in human
      carotid atherosclerotic plaques. We speculate that HCMV may contribute to
      endothelial dysfunction via ARG II induction and reduced eNOS production. 

PMID- 24442488
TI  - Does coronary CT angiography improve risk stratification over coronary artery
      calcium scoring in symptomatic patients with a low pre-test probability of
      coronary artery disease and a CAC of zero? Reply.

PMID- 24442487
TI  - Antiangiogenic therapy of brain tumors: the role of bevacizumab.
AB  - Angiogenesis is one of the hallmarks of cancer, including brain tumors. Malignant
      gliomas have the highest degree of vascular proliferation among solid tumors;
      thus, angiogenic pathways represent an attractive target to interfere with tumor
      growth. Up to date VEGF pathway targeting with specific drugs has yielded
      interesting therapeutics results. In particular bevacizumab, a monoclonal
      antibody against VEGF-A, has shown clinical activity in malignant gliomas,
      especially glioblastomas, in terms of a high response rate on MRI and a
      significant increase in progression-free survival. 

PMID- 24442489
TI  - The intriguing issue of genetic predisposition and the importance of
      identification of pre-clinical markers of endothelial damage in radiotherapy
      induced cardiotoxicity: reply.

PMID- 24442490
TI  - Shaping oral cell plasticity to osteogenic differentiation by human mesenchymal
      stem cell coculture.
AB  - In the context of cell-based oral hard tissue regeneration, especially assumed
      plasticity of oral host tissue cells in response to human mesenchymal stem cells
      (hMSCs), is poorly understood. To investigate this area, we assess osteogenic
      features in various oral cell types during hMSC coculture, including human
      alveolar osteoblasts (hOAs), periodontal ligament cells (hPDLs) and gingival
      fibroblasts (hGFs). Interactive hMSC coculture globally enhanced the
      transcription of osteogenic genes, in all oral cell types under study, as
      revealed by qRT-PCR and did not affect oral cell proliferation compared with
      controls in a transwell coculture system as evaluated by 5-bromo-2'-deoxyuridine
      proliferation assay. 3D gel-derived hMSC cocultures exhibited an abundance of
      bone-related key molecules in oral cells, which followed the ranking hOAs > hGFs
      > hPDLs. Compared to matched controls, this hierarchy also applied for the
      presence of higher amounts of extracellular matrix deposits and mineralization
      nodules in interactive hMSC coculture. Our results show for the first time that
      in the context of prospective periodontal tissue regeneration strategies, hMSCs
      influence oral cells by gradually shaping their plasticity, particularly features
      associated with an osteogenic phenotype. These novel findings contribute another
      piece to the conceptual hMSC action puzzle and valuably support the notion that
      hMSCs trigger osteogenesis in the oral cell context.

PMID- 24442491
TI  - Identification of enteroendocrine cells that express TRPA1 channels in the mouse
      intestine.
AB  - TRPA1 is an ion channel that detects specific chemicals in food and also
      transduces mechanical, cold and chemical stimulation. Its presence in sensory
      nerve endings is well known and recent evidence indicates that it is expressed by
      some gastrointestinal enteroendocrine cells (EEC). The purpose of the present
      work is to identify and quantify EEC that express TRPA1 in the mouse
      gastrointestinal tract. Combined in situ hybridisation histochemistry for TRPA1
      and immunofluorescence for EEC hormones was used. TRPA1 expressing EEC were
      common in the duodenum and jejunum, were rare in the distal small intestine and
      were absent from the stomach and large intestine. In the duodenum and jejunum,
      TRPA1 occurred in EEC that contained both cholecystokinin (CCK) and 5
      hydroxytryptamine (5HT) and in a small number of cells expressing 5HT but not
      CCK. TRPA1 was absent from CCK cells that did not express 5HT and from EEC
      containing glucagon-like insulinotropic peptide. Thus TRPA1 is contained in very
      specific EEC populations. It is suggested that foods such as garlic and cinnamon
      that contain TRPA1 stimulants may aid digestion by facilitating the release of
      CCK.

PMID- 24442492
TI  - Effects of combinations of BMP-2 with FGF-2 and/or VEGF on HUVECs angiogenesis in
      vitro and CAM angiogenesis in vivo.
AB  - Angiogenesis, a complex biologic process, is regulated by a large number of
      angiogenic factors, including vascular endothelial growth factor (VEGF) and
      fibroblast growth factor-2 (FGF-2). Whether Bone morphogenetic proteins-2 (BMP
      2), the osteoinductive factor, could significantly reinforce the effect of VEGF
      and FGF-2 on angiogenesis has not been studied in detail. To study the positive
      effects of multiple growth factors on angiogenesis, HUVECs were treated with BMP
      2, VEGF, or FGF-2 singly and in binary and ternary combinations. This study
      further investigates the optimal timing of the ternary combination of BMP-2, VEGF
      and FGF-2 for angiogenesis in the chorioallantoic membrane (FGF-2 CAM). Results
      of single applications of BMP-2, VEGF, or FGF-2 suggested that HUVECs
      angiogenesis could be promoted in a dose-dependent manner and that the optimal
      concentration of BMP, VEGF and FGF-2 was 10, 50 and 1 ng/mL, respectively. These
      results indicated that the angiogenic activity of VEGF and FGF-2 was amplified by
      combining with BMP-2. The ternary combination of BMP-2, VEGF and FGF-2 exhibited
      a positive and synergistic effect on HUVECs angiogenesis, with the lower
      concentrations of each factor (1 ng/mL of BMP-2, 25 ng/mL of VEGF and 0.1 ng/mL
      of FGF-2) being sufficient to show synergistic promotion. When VEGF and FGF-2
      were added in the initial activation stage and BMP-2 was added in the maturation
      stage, both HUVECs angiogenesis in vitro and CAM angiogenesis in vivo could be
      enhanced more effectively. These results could provide a basis for the controlled
      release systems capable of delivering multiple factors sequentially to promote
      angiogenesis in tissue engineering.

PMID- 24442493
TI  - Utility of point-of-care biliary ultrasound in the evaluation of emergency
      patients with isolated acute non-traumatic epigastric pain.
AB  - To determine the utility of emergency physician-performed point-of-care biliary
      ultrasound in the evaluation of emergency department (ED) patients with isolated
      acute non-traumatic epigastric pain. This was a multi-center prospective
      observational study of adult patients presenting to the ED with isolated acute
      non-traumatic epigastric pain. Patients with abdominal tenderness at any site
      other than the epigastric region, or with a history of gall stones,
      cholecystectomy, gastrointestinal bleeding, chronic abdominal pain, trauma, or
      altered mental status were excluded. Emergency physician investigators performed
      point-of-care biliary ultrasound after clinical assessment. Demographic
      information, history, physical examination findings, laboratory results,
      additional diagnostic tests, and disposition data were collected. A total of 51
      patients (39 women, 12 men) were enrolled. The mean age of the patients was 36.4
      years +/- 13.6 (SD). All subjects had isolated epigastric tenderness. Gallstones
      were found in 20/51 (39%, 95% CI 26-52%) on point-of-care biliary ultrasound. Of
      the 20 patients who had gallstones, eight had sonographic signs of chloecystitis.
      The treating emergency physicians' initial evaluation did not plan to include an
      ultrasound in 17/20 patients with gallstones. 19/20 patients were initially given
      a GI cocktail by the treating emergency physicians. Point-of-care biliary
      ultrasound detected gall stones in more than one-third of ED patients with
      isolated acute non-traumatic epigastric pain. All patients presenting to the ED
      with non-traumatic epigastric pain should be evaluated for biliary disease with
      an ultrasound imaging study. Bedside ultrasound can avoid misdiagnosis and
      expedite management in these patients.

PMID- 24442494
TI  - Irritable bowel syndrome correlates with increased risk of Parkinson's disease in
      Taiwan.
AB  - This study investigated whether an association exists between irritable bowel
      syndrome (IBS) and the risk of Parkinson's disease. This is a retrospective
      cohort study using the dataset of the Taiwan National Health Insurance Program
      from 2000 to 2010. We identified 23,875 patients (aged 20 years or older) with
      newly diagnosed IBS as the IBS group and 95,500 subjects without IBS as the non
      IBS group for comparison. The main outcome was incident Parkinson's disease
      compared between both groups by the end of 2010. We measured the hazard ratio
      (HR) to evaluate the association between IBS and Parkinson's disease. The overall
      incidence of Parkinson's disease in the IBS group was 1.76-fold higher than that
      in the non-IBS group (16.4 vs. 9.33 per 10,000 person-years). The multivariable
      Cox proportional hazards regression analysis revealed that the adjusted HR of
      Parkinson's disease associated with IBS was 1.48 (95% CI 1.27, 1.72), compared
      with the non-IBS group. Age, women, hypertension, dementia, cerebrovascular
      disease and depression were also significantly associated with Parkinson's
      disease. Patients with irritable bowel syndrome are at an increased risk of
      developing Parkinson's disease. Further studies are required to explore the
      pathophysiological connection between these disorders.

PMID- 24442495
TI  - [Transport, distribution and metabolism of auxin in Vicia faba L. roots after
      application of [(14)C]IAA or [ (3)H]IAA to the apical bud].
AB  - After application of [2-(14)C]IAA or [(3)H]IAA to the apical bud of intact young
      broad-beans, the movement of labelled auxin into the roots was followed by liquid
      scintillation counting and by autoradiographic analyses. Its metabolism was
      studied by chromatography, and its pathways by autoradiographic analyses coupled
      with ringing experiments or removal of the stele.The movement of [(14)C]IAA or
      [(3)H]IAA was characterized by a high retention of radioactivity in tissues,
      particularly in very young plants. The speed, which did not exceed 9 mm.h(-1) in
      old roots, appeared the slower the younger the plants were. However, it seemed
      possible that small quantities of IAA or its derivates went into sieve tubes in
      which they moved downwards faster. In the apical part of the root the labelled
      IAA was more quickly transformed than in the other parts of this organ. 24 h
      after the application of the IAA, the labelled molecules gathered more densely in
      the cap itself than in apical meristem.At least 2/3 of the applied auxin moved
      within the stele, which in a crosssection represents only 1/7 of the whole area.
      In the older part of the root, the cambial zone located between mature phloem and
      mature xylem was the preferred pathway of IAA transport, although it is a zone
      where the hormone is immobilized, used and metabolised. In the younger part of
      the root, the whole stele was the preferred pathway. Therefore, the auxin is in a
      privileged situation to take part in the regulation of various processes,
      especially in the development of secondary vascular tissue, more particularly of
      xylem. 

PMID- 24442496
TI  - The conversion of gibberellin A1 to gibberellin A 8 by a cell-free enzyme system.
AB  - An enzyme system which catalyzes hydroxylation of (3)[H]gibberellin A1
      ([(3)H]GA1) to [(3)H]GA8 was obtained from homogenates of germinating bean
      (Phaseolus vulgaris L.) seed. The system remained in the supernatant after
      centrifugation at 95000*g for 2 h. Hydroxylation occurred at one of the
      specifically (3)H-labeled positions (C-2) and, concomitantly, produced
      [(3)H]water whic was used to measure formation of [(3)H]GA8. NADPH and/or
      ascorbate are cofactors utilized by this enzyme. EDTA effectively inhibited the
      system, suggesting a cation requirement. 

PMID- 24442497
TI  - Studies on the release of barley aleurone cell proteins: Kinetics of labelling.
AB  - Protein release from gibberellic acid-treated aleurone cells of barley (Hordeum
      vulgare L.) was followed in pulse-chase experiments with radioactively labelled
      amino acids. After a 10-min pulse of [(3)H]leucine or [(3)H]tryptophan, label was
      incorporated into trichloroacetic-acid (TCA)-insoluble material; some of this was
      released into the incubation medium during a chase with carrier amino acid. This
      relase of TCA-insoluble material into the incubation medium had no appreciable
      lag period. Precipitation with rabbit-anti-alpha-amylase antibody of the
      radioactivity released from aleurone layers into the medium during chasing
      indicates that as much as 70% of the radioactivity present is alpha-amylase.
      Aleurone cell homogenates were fractionated by differential centrifugation after
      pulsing with labelled amino acids. Radioactivity in TCA-insoluble materials was
      distributed equally among all sediment fractions indicating that no specific
      accumulation of label occurred. Tissue was also fractionated after labelling with
      a pulse of [(3)H]tyrosine and [(14)C]-tryptophan, and the distribution of
      radioactivity in various fractions also showed that no preferential sedimentation
      of label occurred. Altogether, no experimental evidence could be found to support
      the hypothesis that proteins are released from aleurone cells via discrete
      secretory organelles. 

PMID- 24442498
TI  - Studies on the release of barley aleurone cell proteins: Autoradiography.
AB  - Both uptake and incorporation of radioactivity from [(3)H]L-leucine into
      gibberellic-acid (GA3)-treated aleurone layers of barley (Hordeum vulgare L.) was
      enhanced by pretreatment with 5 mM potassium bromate. The effect of 5 mM KBrO3 on
      amino-acid incorporation was quantitative rather than qualitative and could be
      partly reversed by the addition of neutralized casein hydrolysate at 10 mg/ml.
      Autoradiographs of GA3-treated aleurone cells pulsed with [(3)H]leucine showed
      distribution of silver grains predominantly over the endoplasmic reticulum (ER)
      and aleurone grains. After chasing with carrier L-leucine for 60 min, fewer
      silver grains were associated with the ER and aleurone grains while nearly half
      of the silver was associated with the ground cytoplasm of the cell.
      Autoradiographs were prepared from aleurone cells previously stratified by
      ultracentrifugation. After a 10-min pulse of label, the silver grains were found
      over the central ER zone of centrifuged cells; however, with an increase in
      duration of the chase, label was found distributed throughout the aleurone grain
      and spherosome region of the cell. The silver grains which were located over the
      central zone of centrifuged cells at the end of the pulse were almost exclusively
      associated with the ER. There is no evidence for association of label with
      dictyosomes or with vesicles derived from dictyosomes. The experimental evidence
      indicates that labelled amino acids are incorporated into aleurone cells on the
      ER and are released from these cells without the participation of a membrane
      bound vesicle. 

PMID- 24442499
TI  - Phytochrome: Immunocytochemical assay of synthesis and destruction.
AB  - The protein moiety of phytochrome, when assayed by an immunocytochemical
      technique, was not detected in dry oat (Avena sativa L., cv. Garry) and rye
      (Secale cereale L., cv. Balbo) grains or in grains hydrated 4 h at 25 degrees .
      After 24 h of hydration immunochemical activity of phytochrome in situ was
      readily detectable. Immunocytochemical assays of destruction show that different
      regions of 3-day-old, single oat and rye seedlings have different destruction
      kinetics. Oat roots apparently exhibit much slower destruction than the rest of
      the seedling, while the nodal region of rye exhibits slower destruction than the
      upper part of the coleoptile. When experimentally feasible, parallel
      spectrophotometric assays of appearance and destruction gave results similar to
      those observed by immunocytochemistry. 

PMID- 24442500
TI  - Extraction of hydroxyproline-containing proteins and pectic substances from cell
      walls of growing and non-growing mung bean hypocotyl segments.
AB  - Elongating upper and non-elongating lower segments of mung bean hypocotyls
      (Phaseolus aureus Roxb.) were compared in their ability to incorporate labelled
      polymers into their cell walls when fed with [(14)C]proline. The non-growing
      segments incorporated more amino acids into the walls and showed a higher degree
      of hydroxylation of the proline residues. The proportion of the [(14)C]polymer
      solubilized by chaotropic or complexing solutes was lower in the non-growing
      segments, possibly because of enhanced formation of covalent crosslinks between
      the glycoprotein and other cell wall constituents.The [(14)C]polymer was
      extracted from the wall by alkali at room temperature after removal of most of
      the hemicellulose by alkali at 0 degrees , regardless of whether or not the
      pectic substances were first removed. The alkali does not extract any of the
      pectic polyuronide. Similar results were obtained with 6 M guanidine thiocyanate,
      which solubilizes appreciable amounts of the glycoprotein at room temperature and
      neutral pH without removing pectic substances.The results are considered to
      indicate a cell wall structure in mung bean hypocotyl tissue in which at least
      part of the pectin and some of the glycoprotein are not linked covalently
      together or to other cell wall constituents. 

PMID- 24442501
TI  - Structural and autoradiographic observations of the infection of tobacco
      protoplasts with pea enation mosaic virus.
AB  - The structural changes accompanying infection of tobacco protoplasts with pea
      enation mosaic virus have been examined by electron microscopy. The first visible
      response to infection is the appearance at about 17 h post inoculation of
      cytoplasmic membrane bound bodies enclosing a series of fibril-containing
      vesicles. At later stages of infection a proportion of these bodies appear to
      fuse with the nuclear membrane. Intact virus is found only within the nucleus.
      The fibrils within the vesicles are digestible by RNAse but not DNAse and they
      may be labelled using [(3)H]uridine. These results are discussed in terms of the
      course of infection of plant cells by viruses. 

PMID- 24442502
TI  - Identification of IAA in phloem and root pressure saps of Ricinus communis L. by
      mass spectrometry.
AB  - Using gas-liquid chromatography and mass spectrometry, IAA was identified in the
      phloem sap and root pressure sap of Ricinus communis L. The bark incision
      procedure for collecting phloem sap was not associated with a significant rise in
      the IAA level in the bark tissues. 

PMID- 24442503
TI  - Abscisic acid in leaves of Hedera helix L.
AB  - Abscisic acid was detected by gas-liquid chromatography of the methyl esters in
      the acid fraction of extracts from leaves of juvenile and adult Hedera helix L.
      Combined gas chromatography-mass spectrometry data were obtained for the extract
      of adult tissues and thin-layer chromatography, gas-liquid chromatography and gas
      chromatography-mass spectrometry data for that of juvenile tissues. An estimation
      of the amounts of abscisic acid present in extracts from both growth phases was
      carried out using a single ion monitoring technique. 

PMID- 24442504
TI  - Bacteriophage recombination systems and biotechnical applications.
AB  - Bacteriophage recombination systems have been widely used in biotechnology for
      modifying prokaryotic species, for creating transgenic animals and plants, and
      more recently, for human cell gene manipulation. In contrast to homologous
      recombination, which benefits from the endogenous recombination machinery of the
      cell, site-specific recombination requires an exogenous source of recombinase in
      mammalian cells. The mechanism of bacteriophage evolution and their coexistence
      with bacterial cells has become a point of interest ever since bacterial viruses'
      life cycles were first explored. Phage recombinases have already been exploited
      as valuable genetic tools and new phage enzymes, and their potential application
      to genetic engineering and genome manipulation, vectorology, and generation of
      new transgene delivery vectors, and cell therapy are attractive areas of research
      that continue to be investigated. The significance and role of phage
      recombination systems in biotechnology is reviewed in this paper, with specific
      focus on homologous and site-specific recombination conferred by the coli phages,
      lambda, and N15, the integrase from the Streptomyces phage, PhiC31, the
      recombination system of phage P1, and the recently characterized recombination
      functions of Yersinia phage, PY54. Key steps of the molecular mechanisms
      involving phage recombination functions and their application to molecular
      engineering, our novel exploitations of the PY54-derived recombination system,
      and its application to the development of new DNA vectors are discussed.

PMID- 24442505
TI  - Nitrite reductase genes as functional markers to investigate diversity of
      denitrifying bacteria during agricultural waste composting.
AB  - The purpose of this study was to investigate the diversity of denitrifier
      community during agricultural waste composting. The diversity and dynamics of the
      denitrifying genes (nirK and nirS) were determined using polymerase chain
      reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Relationships
      between physico-chemical parameters and denitrifying genes structures were
      simultaneously evaluated by redundancy analysis (RDA). Phylogenetic analysis
      indicated that nirK clones grouped into six clusters and nirS clones into two
      major clusters, respectively. The results showed a very high diversity of nir
      gene sequences within composting samples. RDA showed that the nirK and nirS gene
      structures were significantly related to pH and pile temperature (P < 0.05).
      Significant amounts of the variation (49.2 and 38.3 % for nirK and nirS genes,
      respectively) were explained by pH and pile temperature, suggesting that those
      two parameters were the most likely ones to influence, or be influenced by the
      denitrifiers harboring nirK and nirS genes. 

PMID- 24442506
TI  - Proteomic analysis reveals complex metabolic regulation in Saccharomyces
      cerevisiae cells against multiple inhibitors stress.
AB  - Toxic compounds including acids, furans, and phenols (AFP) were generated from
      the pretreatment of lignocellulose. We cultivated Saccharomyces cerevisiae cells
      in a batch mode, besides the cell culture of original yeast strain in AFP-free
      medium which was referred as C0, three independent subcultures were cultivated
      under multiple inhibitors AFP and were referred as C1, C2, and C3 in time
      sequence. Comparing to C0, the cell density was lowered while the ethanol yield
      was maintained stably in the three yeast cultures under AFP stress, and the lag
      phase of C1 was extended while the lag phases of C2 and C3 were not extended. In
      proteomic analysis, 194 and 215 unique proteins were identified as differently
      expressed proteins at lag phase and exponential phase, respectively.
      Specifically, the yeast cells co-regulated protein folding and protein synthesis
      process to prevent the generation of misfolded proteins and to save cellular
      energy, they increased the activity of glycolysis, redirected metabolic flux
      towards phosphate pentose pathway and the biosynthesis of ethanol instead of the
      biosynthesis of glycerol and acetic acid, and they upregulated several
      oxidoreductases especially at lag phase and induced programmed cell death at
      exponential phase. When the yeast cells were cultivated under AFP stress, the new
      metabolism homeostasis in favor of cellular energy and redox homeostasis was
      generated in C1, then it was inherited and optimized in C2 and C3, enabling the
      yeast cells in C2 and C3 to enter the exponential phase in a short period after
      inoculation, which thus significantly shortened the fermentation time. 

PMID- 24442507
TI  - Bacteriophage lambda display systems: developments and applications.
AB  - Bacteriophage (phage) Lambda (lambda) has played a key historic role in driving
      our understanding of molecular genetics. The lytic nature of lambda and the
      conformation of its major capsid protein gpD in capsid assembly offer several
      advantages as a phage display candidate. The unique formation of the lambda
      capsid and the potential to exploit gpD in the design of controlled phage
      decoration will benefit future applications of lambda display where steric
      hindrance and avidity are of great concern. Here, we review the recent
      developments in phage display technologies with phage lambda and explore some key
      applications of this technology including vaccine delivery, gene transfer, bio
      detection, and bio-control. 

PMID- 24442508
TI  - The role of caspase-8 in amyloid-induced beta cell death in human and mouse
      islets.
AB  - AIMS/HYPOTHESIS: Reduced beta cell mass due to increased beta cell apoptosis is a
      key defect in type 2 diabetes. Islet amyloid, formed by the aggregation of human
      islet amyloid polypeptide (hIAPP), contributes to beta cell death in type 2
      diabetes and in islet grafts in patients with type 1 diabetes. In this study, we
      used human islets and hIAPP-expressing mouse islets with beta cell Casp8 deletion
      to (1) investigate the role of caspase-8 in amyloid-induced beta cell apoptosis
      and (2) test whether caspase-8 inhibition protects beta cells from amyloid
      toxicity. METHODS: Human islet cells were cultured with hIAPP alone, or with
      caspase-8, Fas or amyloid inhibitors. Human islets and wild-type or hIAPP
      expressing mouse islets with or without caspase-8 expression (generated using a
      Cre/loxP system) were cultured to form amyloid. Caspase-8 and -3 activation, Fas
      and FLICE inhibitory protein (FLIP) expression, islet beta cell and amyloid area,
      IL-1beta levels, and the beta:alpha cell ratio were assessed. RESULTS: hIAPP
      treatment induced activation of caspase-8 and -3 in islet beta cells (via Fas
      upregulation), resulting in apoptosis, which was markedly reduced by blocking
      caspase-8, Fas or amyloid. Amyloid formation in cultured human and hIAPP
      expressing mouse islets induced caspase-8 activation, which was associated with
      Fas upregulation and elevated islet IL-1beta levels. hIAPP-expressing mouse
      islets with Casp8 deletion had comparable amyloid, IL-1beta and Fas levels with
      those expressing hIAPP and Casp8, but markedly lower beta cell apoptosis, higher
      beta:alpha cell ratio, greater beta cell area, and enhanced beta cell function.
      CONCLUSIONS/INTERPRETATION: Beta cell Fas upregulation by endogenously produced
      and exogenously applied hIAPP aggregates promotes caspase-8 activation, resulting
      in beta cell apoptosis. The prevention of amyloid-induced caspase-8 activation
      enhances beta cell survival and function in islets.

PMID- 24442510
TI  - Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora's box.
AB  - Over a century ago, inquisitive physicians made remarkable discoveries regarding
      pancreatic pathology in individuals with diabetes, including those who were
      likely afflicted with the type 1 (autoimmune) form of the disease. Those studies
      of post-mortem tissues noted unique anatomical changes in islet architecture as
      well as the presence of unusual cellular infiltrates. In the time since,
      investigations of pancreatic pathology have, with near uniformity, been
      restricted to analysis of organs obtained post-mortem. While clearly beneficial
      for addressing questions of the disorder's pathogenesis, concern exists regarding
      potential artefacts that might occur through analysis of tissues that have been
      recovered hours, often many hours, following death. Beyond this, studies of
      tissues obtained long after the diagnosis of type 1 diabetes may not disclose
      important physiological events occurring at onset or even earlier in the natural
      history of disease, before symptomatic hyperglycaemia. To this end, Krogvold and
      colleagues (in this issue of Diabetologia, doi: 10.1007/s00125-013-3155-y)
      undertook a potentially high-reward strategy involving pancreatic biopsy in
      living adults with recent-onset type 1 diabetes. Procedures were performed under
      informed consent, undertaken based on recent improvements in laparoscopic
      techniques, and carried out by individuals with considerable surgical experience.
      These efforts were terminated for ethical reasons following the occurrence of
      serious complications (including post-operative bleeding and pancreatic leakage).
      The experience lends itself to analogy with the Greek myth of Pandora's box where
      curiosity, in terms of a desire to see what resided inside a closed container,
      unleashed a series of ills on humans once the container was opened. In
      considering the moral of that myth, one must question whether the secrets of the
      pancreas in those living with type 1 diabetes should, for now, remain a mystery
      as the process of manipulating that organ for the purpose of curiosity does not
      occur without harm.

PMID- 24442509
TI  - Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283
      individuals.
AB  - AIMS/HYPOTHESIS: According to genome-wide association studies (GWAS) a locus in
      the HNF1A gene has pleiotropic effects on several metabolic traits. In a large
      single-centre study we used the intronic variant rs1183910 located in a region
      with no or low recombination rate as an instrument for the HNF1A locus to
      evaluate pleiotropic effects of this locus on the risk of developing type 2
      diabetes, as well as on body composition and levels of non-fasting glucose,
      lipids, acute-phase reactants, and biomarkers of liver and pancreas function.
      METHODS: We investigated 60,283 individuals from the Danish general population
      who were all examined in the same laboratory, comprising the Copenhagen General
      Population Study. RESULTS: We confirm previous GWAS findings, namely that the
      minor rs1183910 A allele is associated with an increased risk of developing type
      2 diabetes (p(trend) = 0.003), decreased levels of C-reactive protein (CRP;
      p(trend) = 6 * 10(-76)) and gamma-glutamyltransferase (p(trend) = 4 * 10(-48)),
      and increased levels of total cholesterol (p(trend) = 3 * 10(-10)) and LDL
      cholesterol (p(trend) = 3 * 10(-11)). For the first time, we report that the
      minor rs1183910 A allele is associated with increased levels of non-fasting
      plasma glucose (p(trend) = 3 * 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 *
      10(-4)) and alkaline phosphatase (p(trend) = 5 * 10(-14)), and decreased levels
      of bilirubin (p trend = 3 * 10(-5)). Our results suggest that the association
      with increased risk of type 2 diabetes is driven by high non-fasting glucose
      levels. CONCLUSIONS/INTERPRETATION: The minor rs1183910 A allele prompts a
      potential adverse metabolic profile with increased levels of non-fasting glucose,
      total cholesterol, LDL-cholesterol, ApoB, and alkaline phosphatase, but
      simultaneously has potential beneficial effects through decreased levels of CRP,
      gamma-glutamyltransferase and bilirubin.

PMID- 24442511
TI  - The link between border crossing and obesity.
AB  - Research examining border crossing and health has focused on substance abuse,
      healthcare utilization and air pollution. Living in border communities allows for
      frequent crossing and exposure to different sociocultural and structural
      environments. Given high rates of obesity among Latinos and the large percentage
      living in border communities, it is important to consider the relationship
      between border crossing and obesity. This study explored the relationship between
      frequency of border crossing, obesigenic behaviors, measured obesity, and chronic
      disease. Multistage sampling methods were used to recruit 397 Latino adults
      living in border communities in South San Diego County. Selected participants
      completed a face-to-face interview and height and weight measurements. More
      frequent border crossing was associated with more fast food consumption and a
      greater reported diagnosis of high cholesterol. Understanding the extent to which
      border crossing is associated with obesigenic behaviors and chronic disease is
      important for developing relevant interventions along the border. 

PMID- 24442512
TI  - Erratum to: Evaluating the Impact of Immigration Policies on Health Status Among
      Undocumented Immigrants: A Systematic Review.
AB  - Erratum to: J Immigrant Minority Health, DOI 10.1007/s10903-013-9968-4. One of
      the co-author's name was erroneously submitted and published without middle name,
      as Scott Rhodes, it should be Scott D. Rhodes.

PMID- 24442514
TI  - Stage of change and motivation to healthy diet and habitual physical activity in
      type 2 diabetes.
AB  - Lifestyle changes to healthy diet (HD) and habitual physical activity (HPA) are
      recommended in type 2 diabetes mellitus (T2DM). Yet, for most people with
      diabetes, it may be difficult to start changing. We investigated the stage of
      change toward healthier lifestyles according to Prochaska's model, and the
      associated psychological factors in T2DM patients, as a prerequisite to improve
      strategies to implement behavior changes in the population. A total of 1,353
      consecutive outpatients with T2DM attending 14 tertiary centers for diabetes
      treatment completed the validated EMME-3 questionnaire, consisting of two
      parallel sets of instruments to define the stage of change for HD and HPA,
      respectively. Logistic regression was used to determine the factors associated
      with stages that may hinder behavioral changes. A stage of change favoring
      progress to healthier behaviors was more common in the area of HD than in HPA,
      with higher scores in action and maintenance. Differences were observed in
      relation to gender, age and duration of disease. After adjustment for
      confounders, resistance to change toward HD was associated with higher body mass
      index (BMI) (odds ratio (OR) 1.05; 95 % confidence interval (CI) 1.02-1.08).
      Resistance to improve HPA also increased with BMI (OR 1.06; 95 % CI 1.03-1.10)
      and decreased with education level (OR 0.74; 95 % CI 0.64-0.92). Changing
      lifestyle, particularly in the area of HPA, is not perceived as an essential part
      of treatment by many subjects with T2DM. This evidence must be considered when
      planning behavioral programs, and specific interventions are needed to promote
      adherence to HPA. 

PMID- 24442517
TI  - Lead (Pb) and copper (Cu) share a common uptake transporter in the unicellular
      alga Chlamydomonas reinhardtii.
AB  - The unicellular alga Chlamydomonas reinhardtii has a very high rate of lead (Pb)
      internalization and is known to be highly sensitive to dissolved Pb. However, the
      transport pathway that this metal uses to cross cellular membranes in microalgae
      is still unknown. To identify the Pb(2+) transport pathway in C. reinhartdii, we
      performed several competition experiments with environmentally relevant
      concentrations of Pb(2+) (~10 nM) and a variety of divalent cations. Among the
      essential trace metals tested, cobalt, manganese, nickel and zinc had no effect
      on Pb internalization. A greater than tenfold increase in the concentrations of
      the major ions calcium and magnesium led to a slight decrease (~34 %) in short
      term Pb internalization by the algae. Copper (Cu) was even more effective: at a
      Cu concentration 50 times higher than that of Pb, Pb internalization by the algae
      decreased by 87 %. Pre-exposure of the algae to Cu showed that the effect was not
      due to a physiological effect of Cu on the algae, but rather to competition for
      the same transporter. A reciprocal effect of Pb on Cu internalization was also
      observed. These results suggest that Cu and Pb share a common transport pathway
      in C. reinhardtii at environmentally relevant metal concentrations. 

PMID- 24442518
TI  - Evidences for structural basis of altered ascorbate peroxidase activity in
      cadmium-stressed rice plants exposed to jasmonate.
AB  - Binding interactions of cadmium (Cd) with rice ascorbate peroxidase (OsAPX) in
      presence or absence of jasmonate was examined in-silico. OsAPX is a 250 amino
      acid long protein with 90 % sequence similarity to soybean-APX. The 3D model of
      OsAPX obtained by homology modeling using soybean APX (PDBID:1OAF) as template
      was associated with -15975.85 kJ/mol energy, 100 % residues in favoured region,
      verify score of 0.85, ERRAT score 89.625 and a negative ProSA graph, suggesting
      OsAPX model to be of good quality, robust and reliable which was submitted with
      Protein Model Database with PMDBID: PM0078091. The rice ascorbate peroxidase
      ascorbate [OsAPX-Asc] complex had a substrate binding cavity involving residues
      at position (30)KSCAPL(35), (167)RCH(169) and (172)R wherein ascorbate
      accommodated via three H-bonds involving (30)Lys at the gamma-edge of heme.
      (169)His served as a bridge between heme-porphyrin of OsAPX and ascorbate
      creating a charge relay system. Cd bound in [OsAPX-Asc-Cd] complex at
      (29)EKSCAPL(35), a site similar to ascorbate binding site. The binding of Cd
      caused breaking of (169)His bridge shifting the protein conformation. Cadmium
      exhibited four electrostatic interactions via (29)Glu of OsAPX backbone. Docking
      of [OsAPX-Asc] with jasmonic acid (JA) resulted in [OsAPX-Asc-JA] complex where 4
      H-bonds held JA to OsAPX in a cavity at gamma-edge on the distal side of heme.
      The binding of [OsAPX-Asc-JA] to Cd show the metal to bind at a position other
      than that involved in binding of OsAPX with Cd alone. Results indicate that Cd
      does not replace iron or ascorbate or JA but binds to OsAPX on the surface at a
      separate site electrostatically. In presence of JA the interactions involved in
      formation of [OsAPXAsc] are restored which is otherwise altered by the presence
      of Cd. The formation and reformation of H-bond take place between the [OsAPX-Asc]
      and Cd/JA. It is the interaction between heme and ascorbate which is modulated
      differently in presence of Cd/JA. In absence of JA, Cd-binds to the [OsAPX-Asc]
      complex at the proximal end of APX near Asc-binding site, whereas in presence of
      JA, Cd-binds on the opposite site of the Asc-binding site involving (30)Lys and
      (29)Glu residues. In-silico binding studies well correlate with the wet-lab
      results where exogenous application of JA increased the activity of OsAPX in rice
      grown under Cd-stress. Therefore it is concluded that the activity of OsAPX in
      rice roots and shoots are compromised under Cd-stress alone.

PMID- 24442516
TI  - Cloning of Hsp21 gene and its expression in Chinese shrimp Fenneropenaeus
      chinensis in response to WSSV challenge.
AB  - In the present study, a DNA sequence encoding a small heat shock protein gene
      (FcHsp21) in the Chinese shrimp, Fenneropenaeus chinensis, was cloned, and its
      expression was analyzed after white spot syndrome virus (WSSV) infection. The
      FcHsp21 gene contained an open reading frame (ORF) of 555 bp in length, encoding
      a 184 amino acid protein with a theoretical size of about 21 kDa and a predicted
      isoelectric point of 5.38. The mRNA of the Hsp21 had a long Poly(A) tail (748 bp)
      with six polyadenylation signals (AATAA) downstream from the terminator. In
      addition, the gene contained a relatively long intron (507 bp), which has not
      been described in shrimps. The intron contained a long compound type
      microsatellite repeat sequence. The analysis of the phylogenetics revealed that
      the Hsp21 was highly conserved among the genomes of animals. Our results show
      that the expression modes of FcHsp21 can be changed by different WSSV infection
      methods. The expression of FcHsp21 was inhibited by muscle-injecting WSSV, but
      induced by feeding WSSV. 

PMID- 24442520
TI  - Impact of molecular alterations of BRAF in the pathogenesis of thyroid cancer.
AB  - BRAF alterations represent a novel indicator of the progression and
      aggressiveness of thyroid carcinogenesis. So, the main aim of the study was to
      elucidate the involvement of BRAF gene mutations and its expression in Kashmiri
      (North India) patients and investigate their association with clinico
      pathological characteristics. Mutational analysis of BRAF gene was performed by
      polymerase chain reaction followed by DNA sequencing, whereas analysis of BRAF
      protein expression was done by western blotting. Overall mutations in BRAF was
      found to be 25% (15 of 60) and all of them were transversions (T>A) affecting
      codon 600 (valine to glutamine), restricted only to papillary thyroid cancer and
      well-differentiated grade. Patients with well-differentiated disease and in
      particular elevated thyroid-stimulating hormone levels were significantly
      associated with BRAF mutations (P < 0.05). Overall, 90% (54 of 60) of thyroid
      cancer cases showed increased expression of BRAF and non-smokers being
      significantly associated with BRAF over-expression. Totally, 86.7% (13 of 15) of
      BRAF mutation-positive patients were having over-expression of BRAF protein,
      whereas 91.2% (41 of 45) of patients with wild-type BRAF status were having over
      expressed BRAF protein (P > 0.05). We conclude that both mutational events as
      well as over-expression of BRAF gene is highly implicated in pathogenesis of
      thyroid cancer and the BRAF protein over-expression is independent of the BRAF
      mutational status of thyroid cancer patients. 

PMID- 24442521
TI  - An annotated bibliography in managed care for psychiatric residents and faculty.
AB  - A computerized search of the literature on managed care was done using the Health
      Planning and Administration and the MEDLINE databases. There were 1,892 articles
      indexed between 1987 and 1993. Additional citations were retrieved through a
      manual literature search. On the basis of this information, a reading list was
      compiled for psychiatric residents and faculty. Several psychiatrists were
      consulted during the selection process. It is important to teach the principles
      of managed care to psychiatric residents and integrate managed care practice into
      medical school and residency training, and for this purpose the annotated
      bibliography will serve as a useful instructional tool. 

PMID- 24442519
TI  - An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects.
AB  - DNA variation in Interferon Regulatory Factor 6 (IRF6) causes Van der Woude
      syndrome (VWS), the most common syndromic form of cleft lip and palate (CLP).
      However, an etiologic variant in IRF6 has been found in only 70% of VWS families.
      To test whether DNA variants in regulatory elements cause VWS, we sequenced three
      conserved elements near IRF6 in 70 VWS families that lack an etiologic mutation
      within IRF6 exons. A rare mutation (350dupA) was found in a conserved IRF6
      enhancer element (MCS9.7) in a Brazilian family. The 350dupA mutation abrogated
      the binding of p63 and E47 transcription factors to cis-overlapping motifs, and
      significantly disrupted enhancer activity in human cell cultures. Moreover, using
      a transgenic assay in mice, the 350dupA mutation disrupted the activation of
      MCS9.7 enhancer element and led to failure of lacZ expression in all head and
      neck pharyngeal arches. Interestingly, disruption of the p63 Motif1 and/or E47
      binding sites by nucleotide substitution did not fully recapitulate the effect of
      the 350dupA mutation. Rather, we recognized that the 350dupA created a CAAAGT
      motif, a binding site for Lef1 protein. We showed that Lef1 binds to the mutated
      site and that overexpression of Lef1/beta-Catenin chimeric protein repressed
      MCS9.7-350dupA enhancer activity. In conclusion, our data strongly suggest that
      350dupA variant is an etiologic mutation in VWS patients and disrupts enhancer
      activity by a loss- and gain-of-function mechanism, and thus support the
      rationale for additional screening for regulatory mutations in patients with CLP.

PMID- 24442522
TI  - Family therapy education for psychiatry residents : a pilot study of efficacy.
AB  - Teaching and clinical supervision of family therapy can enhance a resident's
      clinical skills and also promote movement from a linear, reductionistic type of
      thinking to a dynamic understanding of complex systems. Second-year postgraduate
      residents who completed a 10-month family therapy program were tested for their
      ability to understand family systems dynamics with the Family Therapy Assessment
      Exercise. Comparison of their test results before and after the program indicated
      significant improvement, which was entirely accounted for by improvement in the
      area of therapeutic skills. 

PMID- 24442513
TI  - Neuronal calcium signaling: function and dysfunction.
AB  - Calcium (Ca(2+)) is an universal second messenger that regulates the most
      important activities of all eukaryotic cells. It is of critical importance to
      neurons as it participates in the transmission of the depolarizing signal and
      contributes to synaptic activity. Neurons have thus developed extensive and
      intricate Ca(2+) signaling pathways to couple the Ca(2+) signal to their
      biochemical machinery. Ca(2+) influx into neurons occurs through plasma membrane
      receptors and voltage-dependent ion channels. The release of Ca(2+) from the
      intracellular stores, such as the endoplasmic reticulum, by intracellular
      channels also contributes to the elevation of cytosolic Ca(2+). Inside the cell,
      Ca(2+) is controlled by the buffering action of cytosolic Ca(2+)-binding proteins
      and by its uptake and release by mitochondria. The uptake of Ca(2+) in the
      mitochondrial matrix stimulates the citric acid cycle, thus enhancing ATP
      production and the removal of Ca(2+) from the cytosol by the ATP-driven pumps in
      the endoplasmic reticulum and the plasma membrane. A Na(+)/Ca(2+) exchanger in
      the plasma membrane also participates in the control of neuronal Ca(2+). The
      impaired ability of neurons to maintain an adequate energy level may impact
      Ca(2+) signaling: this occurs during aging and in neurodegenerative disease
      processes. The focus of this review is on neuronal Ca(2+) signaling and its
      involvement in synaptic signaling processes, neuronal energy metabolism, and
      neurotransmission. The contribution of altered Ca(2+) signaling in the most
      important neurological disorders will then be considered. 

PMID- 24442523
TI  - The perceived long-term impact of a psychiatry clerkship on personal growth and
      clinical skills.
AB  - The authors investigated the effects of a psychiatry clerkship that over 14 years
      has had a constant training philosophy and faculty and has been located in the
      same acute general hospital setting. In the study, 169 graduates completed a
      questionnaire on the effects of the clerkship on their knowledge of psychiatry,
      management of emotional problems in their patients, and personal development.
      Based on the graduates' responses, the results reveal that the clerkship indeed
      has had a lasting impact on its former students. Possible implications for
      recruitment of students into psychiatry are discussed. 

PMID- 24442524
TI  - Psychiatry Today : Biology vs. Psychology.
AB  - This research addresses preferences and theoretical leanings of present-day
      psychiatrists along the continuum defined at one end by biology and at the other
      by psychology. A questionnaire was devised and sent to 5,702 randomly selected
      members of the American Psychiatric Association in 1990. The response rate was
      307%. The results were analyzed for two groups: psychiatrists with fewer than 15
      years of practice since residency and psychiatrists with more than 15 years of
      practice since graduation. Although the great majority of psychiatrists in both
      groups equally valued psychology and biology, the senior group attributed a
      greater importance to psychological methods, whereas the younger group stressed
      equally the importance of biology and psychology. This suggests that psychiatry
      has evolved over the years from a predominantly psychological practice to one
      with a more equal emphasis on psychology and biology. Recent advances in
      neuroscience may have shifted the pendulum toward a more balanced willingness of
      clinicians to consider the broad armamentarium of psychosocial and biological
      treatments. The results point to the need for further conceptualization into the
      relationship between biology and psychology and its incorporation into the
      psychiatric residency curriculum. 

PMID- 24442525
TI  - What is a balanced program?
AB  - "Balance" has become the watchword of psychiatry programs. It seems that almost
      all residency training programs claim to be balanced. But what do we mean by this
      term? This article summarizes the author's evolving thinking about what makes for
      a balanced program and suggests that diversity may be a better term. The author
      advocates that balance is not as simple as teaching both psychodynamics and
      biological psychiatry. Instead, it entails a considered, intellectual approach
      that involves long-term vs. other psychotherapies, neuro-science vs.
      psychopharmacology, theoretical pharmacology vs. practical pharmacology, social
      psychiatry vs. treating minority patients, representing all viewpoints in
      psychiatry vs. integrating them. 

PMID- 24442526
TI  - Medical students as role-playing patients : a model for teaching personality
      styles in the medical setting.
AB  - "Personality Styles in the Medical Setting," a seminar at the University of
      California San Francisco School of Medicine during the third-year psychiatric
      clerkship, has proved efficient, educational, and enjoyable for students and
      instructor. The seminar teaches an approach to ivorking with a variety of patient
      personality styles in medical settings. Students role-play patients and doctors
      during simulated medical interviews, using special Patient Profile Sheets as
      guidelines for specific personality styles. In postinterview discussions, the
      students learn a process for gaining insight into the patient's behavior and the
      doctor's common reactions. A Doctor Review Sheet summarizes effective ways to
      work with that personality type to achieve a good doctor-patient relationship
      that will ultimately contribute to better medical care. 

PMID- 24442527
TI  - Demystifying psychiatric research: use of a simulation.

PMID- 24442528
TI  - Frequently asked questions about being a chairperson of a department of
      psychiatry.

PMID- 24442530
TI  - Videos of Sigmund Freud's Most Famous Cases.

PMID- 24442532
TI  - Effect of cup feeding and bottle feeding on breastfeeding in late preterm
      infants: a randomized controlled study.
AB  - BACKGROUND: Cup feeding has been used as an alternative feeding method for
      preterm infants. OBJECTIVE: The purpose of this study was to determine the effect
      of bottle and cup feeding on exclusive breastfeeding rates at hospital discharge
      and 3 and 6 months post-discharge in late preterm infants. METHODS: Included in
      the study were preterm infants of 32 to 35 weeks' gestation fed only by
      intermittent gastric tube at the time of recruitment; 522 infants were randomly
      assigned to 2 groups: the cup-fed group (n = 254) and bottle-fed group (n = 268).
      Main outcomes were prevalence of exclusive breastfeeding at discharge and 3 and 6
      months after discharge, and length of hospital stay. RESULTS: Infants randomized
      to cup versus bottle feeding were more likely to be exclusively breastfed at
      discharge home (relative risk [RR], 1.58; 95% confidence interval [CI], 1.36
      1.83), 3 months after discharge (RR, 1.64; 95% CI, 1.42-1.89), and 6 months after
      discharge (RR, 1.36; 95% CI, 1.14-1.63). There was no significant difference
      between groups for length of hospital stay. The mean hospital stay was 25.96 +/-
      2.20 days in the bottle-fed group and 25.68 +/- 2.22 days in the cup-fed group.
      There was no significant difference between groups for time spent feeding,
      feeding problems, or weight gain in hospital. CONCLUSION: Cup feeding
      significantly increased the likelihood of late preterm infants being exclusively
      breastfed at discharge and 3 and 6 months after discharge, and cup feeding did
      not increase the length of hospital stay. Overall, we recommend cup feeding as a
      transitional method prior to breastfeeding for late preterm infants during
      hospitalization.

PMID- 24442531
TI  - Use of cognitive interviews in the development of the PLUS-M item bank.
AB  - PURPOSE: Measuring constructs such as mobility with patient-reported outcomes
      (PROs) can enhance clinical and scientific understanding of how health
      conditions, like lower limb amputation, impact patients' lives. When developing
      PRO questionnaires, cognitive interviews (CIs) are used to examine whether survey
      items are understandable, clear, and meaningful. The aim of this study was to use
      CIs to inform item development for the Prosthetic Limb Users Survey of Mobility
      (PLUS-M), a PRO that measures mobility in prosthetic limb users. METHODS: Thirty
      six CIs were conducted with 30 prosthetic limb users. Each participant responded
      to up to 30 items from the PLUS-M candidate item set. Each item was reviewed by a
      minimum of five participants who differed in self-reported mobility, literacy,
      level of amputation, and time since amputation. Items were revised based on
      participant feedback, and substantially revised items were re-evaluated through
      additional CIs. RESULTS: Feedback from CIs identified substantial issues in 76 of
      the total 156 items. These items were subsequently modified or eliminated.
      CONCLUSION: Cognitive interviews were an essential qualitative step in the
      development of the PLUS-M item bank and resulted in better functioning items.

PMID- 24442533
TI  - Development of a high-resolution YSO gamma camera system that employs 0.8-mm
      pixels.
AB  - OBJECTIVE: YSO (Ce-doped Y2SiO5) is a promising scintillator for a single-photon
      imaging system since it has relatively high light output and does not contain any
      natural radioactivity. Since YSO is not hygroscopic, it may be possible to
      fabricate a block with small pixels for a high-resolution system. For this
      purpose, we developed a high-resolution gamma camera system that employs smaller
      than 1-mm YSO pixels. METHODS: The gamma camera's detector used 0.8 * 0.8 * 7-mm
      YSO pixels. All the surfaces of these YSO pixels were mechanically polished,
      combined with a 0.1-mm-thick BaSO4 reflector to form a 48 * 48 matrix, and
      optically coupled to a high quantum efficiency, 2-inch square position sensitive
      photomultiplier tube (Hamamatsu Photonics H10966 A-100). The YSO block was 43.2 *
      43.2 mm. The YSO gamma camera was encased in a 5-mm-thick tungsten container, and
      a parallel collimator was mounted on its front. The parallel hole collimator was
      made of a 3-layer (each layer was 5-mm thick) tungsten plate, and each plate had
      48 * 48, 0.6-mm holes that were positioned by one-to-one coupling with the YSO
      pixels. RESULTS: Even with the 0.8-mm YSO pixels, we clearly resolved most of the
      pixels in a 2-dimensional histogram with a peak-to-valley ratio of 2.9 for the
      122-keV gamma photons. The energy resolution was 20.4% FWHM. The spatial
      resolutions with a parallel hole collimator 2 mm from the collimator surface were
      0.7- and 1.3-mm FWHM for the 122- and ~35-keV gamma photons, respectively. We
      successfully obtained phantoms and small animal images with our YSO gamma camera
      system. CONCLUSION: Our high-resolution system has a potential to be useful for
      molecular imaging research.

PMID- 24442535
TI  - MicroRNAs horizon in retinoblastoma.
AB  - In the retinoblastoma research, it is of great interest to identify molecular
      markers associated with the genetics of tumorigenesis. microRNAs (miRNAs) are
      small non-coding RNA molecules that play a regulatory role in many crucial
      cellular pathways such as differentiation, cell cycle progression, and apoptosis.
      A body of evidences showed dysregulation of miRNAs in tumor biology and many
      diseases. They potentially play a significant role in tumorigenesis processes and
      have been the subject of research in many types of cancers including retinal
      tumorigenesis. miRNA expression profiling was found to be associated with tumor
      development, progression and treatment. These associations demonstrate the
      putative applications of miRNAs in monitoring of different aspect of tumors
      consisting diagnostic, prognostic and therapeutic. Herein, we review the current
      literature concerning to the study of miRNA target recognition, function to
      tumorigenesis and treatment in retinoblastoma. Identification the specific miRNA
      biomarkers associated with retinoblastoma cancer may help to establish new
      therapeutic approaches for salvage affected eyes in patients. 

PMID- 24442534
TI  - Temporal trends of element concentrations and ecophysiological parameters in the
      lichen Pseudevernia furfuracea transplanted in and around an industrial area of S
      Italy.
AB  - This study investigated the temporal trends of element concentrations and
      ecophysiological parameters (integrity of cell membranes, membrane lipid
      peroxidation, and sample vitality) in thalli of the lichen Pseudevernia
      furfuracea transplanted in and around an industrial area of S Italy from May 2010
      to May 2011, once every 3 months. Element accumulation at levels indicating that
      the atmosphere of the study area was polluted by most elements occurred only
      during the third trimester of exposure, and the ecophysiological parameter best
      reflecting this trend was sample vitality expressed in terms of activity of the
      enzyme dehydrogenase. Among the available climatological parameters, the
      different amount of rainfall during the exposure period may influence the
      results, especially the number of hours with rainfall >16 mm/day, which is the
      threshold between light-moderate and moderate-heavy rainfall in the Mediterranean
      area.

PMID- 24442536
TI  - Chronic effect of gabapentin on liver function in adult male rats.
AB  - Gabapentin (GPN) is a new antiepileptic agent currently in used as add-on therapy
      in adult patients suffering from partial seizures. The extent of liver damage at
      different dosage and long term treatment with GPN is not yet clear. Therefore
      this study was undertaken to find out the possibility of liver damage by this
      drug. Adult male (Wistar) rats of 180-220 g were administered intraperitoneally
      with GPN (20 or 100 mg/kg) for 45 days. After the experimental period, the liver
      function tests were carried out in control and experimental groups. The activity
      of liver enzymes, with 20 mg/kg of GPN were not significantly different from the
      control group but, the serum levels of aspartate aminotransferase, alanine
      aminotransferase, alkaline phosphatase, lactate dehydrogenase, direct bilirubin
      and total bilirubin were enhanced significantly with 100 mg/kg of GPN. Total
      protein and albumin decreased in this group as compared with control animals. The
      histopathology of the liver parenchymal cells also showed minute foci of necrosis
      in a few rats treated with high dose of GPN, whereas, at therapeutic dose the
      histopathology and biochemical indices showed almost normal values. At
      therapeutic dose GPN is a safer drug with regards to liver function and
      hepatocellular damage as compared with other antiepileptic drugs. 

PMID- 24442537
TI  - Differential expression of human homeodomain TGIFLX in brain tumor cell lines.
AB  - Glioblastoma is the most common and the most lethal primary brain cancer. This
      malignancy is highly locally invasive, rarely metastatic and resistant to current
      therapies. Little is known about the distinct molecular biology of glioblastoma
      multiforme (GBM) in terms of initiation and progression. So far, several
      molecular mechanisms have been suggested to implicate in GBM development.
      Homeodomain (HD) transcription factors play central roles in the expression of
      genomic information in all known eukaryotes. The TGIFX homeobox gene was
      originally discovered in human adult testes. Our previous study showed
      implications of TGIFLX in prostate cancer and azoospermia, although the molecular
      mechanism by which TGIFLX acts is unknown. Moreover, studies reported that HD
      proteins are involved in normal and abnormal brain developments. We examined the
      expression pattern of TGIFLX in different human brain tumor cell lines including
      U87MG, A172, Daoy and 1321N1. Interestingly, real time RT-PCR and western blot
      analysis revealed a high level of TGIFLX expression in A172 cells but not in the
      other cell lines. We subsequently cloned the entire coding sequence of TGIFLX
      gene into the pEGFP-N1 vector, eukaryotic expression vector encoding eGFP, and
      transfected into the U-87 MG cell line. The TGIFLX-GFP expression was confirmed
      by real time RT-PCR and UV-microscopic analysis. Upon transfection into U87
      cells, fusion protein TGIFLX-GFP was found to locate mainly in the nucleus. This
      is the first report to determine the nuclear localization of TGIFLX and
      evaluation of its expression level between different brain tumor cell lines. Our
      data also suggest that TGIFLX gene dysregulation could be involved in the
      pathogenesis of some human brain tumors. 

PMID- 24442538
TI  - Safety of intramedullary autologous peripheral nerve grafts for post
      rehabilitated complete motor spinal cord injuries: a phase I study.
AB  - Many experimental studies have reported behavioral improvement after
      transplantation of peripheral nerve tissue into the contused spinal cord, even in
      large animals. The safety of this treatment in human remains unknown. In this
      translational phase 1 study, safety of peripheral nerve grafting for chronic
      spinal cord injuries and possible outcomes are being reported. Twelve complete
      motor spinal cord injury patients, who had finished their rehabilitation program,
      were enrolled. There were 4 thoracic and 8 cervical cases. Patients underwent
      sural nerve preconditioning in the calf, followed 1 week later, by intramedullary
      transplantation of the harvested nerve fascicles. The patients were followed up
      for potential complications periodically, and final assessment by American Spinal
      Injury association (ASIA) and Spinal Cord Independence Measure (SCIM) III were
      reported after 2 years of follow-up. The median duration of the spinal cord
      injury was 31 months. At two years of follow up, out of 7 cases with ASIA
      Impairment Scale (AIS) A, 4(57.1%) cases improved to AIS B and 1 (14.3%) case
      became AIS C. There were 1 patient with transient increased spasm, one case of
      transient cystitis, 3 patients with transient increased neuropathic pain and 1
      case with transient episode of autonomic dysreflexia, all being managed
      medically. There was no case of donor site infection. The above complications
      were transient as they responded to temporary medical treatment. It may be
      deduced that after two years follow-up of patients that the procedure may be
      safe, however further controlled studies are needed to prove its efficacy.

PMID- 24442539
TI  - The impact of alendronate on bone mineral density of osteoporotic patients.
AB  - The present study assessed the real life therapeutic effects of weekly doses of
      alendronate in treating a group of osteoporotic patients in Iran. The present
      historical cohort was conducted on patients who had undergone two or more bone
      mineral densitometry within an interval of 1.5-2 years in Shariati Hospital bone
      mineral density department between 2002 and 2010.patients were asked by phone
      about consumption of alendronate. The mean increase in the BMD values at
      different sites was calculated. There was a significant increase in the body mass
      index (BMI) values of both the individuals taking alendronate and the control
      group (P<0.001). Taking the weekly dosage of the drug was associated with a 7.67%
      increase in the BMD values at the femoral neck, 8.68% at the total hip, and 3.17%
      at the lumbar spine. Moreover, our results showed a significant difference
      between the height decline in the two groups (alendronate taking: 0.7+/-2.4 vs.
      control: -0.7+/-2.6, P<0.001). Comparing the results of the present study with
      that of previous ones revealed the drug is beneficial in improving bone mineral
      density in Iranians; as well alendronate is more effective in Iranian
      postmenopausal women when compared with the Americans. 

PMID- 24442540
TI  - Can preoperative serum level of creatinine predict new-onset atrial fibrillation
      in non-diabetic male patients undergoing open heart surgery? A retrograde view.
AB  - Renal dysfunction is a risk marker in patients who candidate for coronary artery
      bypass graft (CABG). Renal disorder is associated with prolonged stays in
      intensive care unit and hospital, morbidity and mortality. Aim of this study is
      specific evaluation of association between preoperative creatinine (Cr) with
      atrial fibrillation (AF) after elective off-pump CABG in non-diabetic male
      patients with normal ejection fraction. Two hundred non-diabetic male patients
      with normal ejection fraction undergoing elective off pump CABG surgery enrolled
      in this cross-sectional study and were stratified by present or absence of
      postoperative atrial fibrillation: patients with postoperative new-onset atrial
      fibrillation (n=100) as group 1 and patients without new-onset postoperative
      atrial fibrillation as group 2 (n=100). Preoperative serological test of the
      participants, such as serum creatinine, were recorded in their medical dossiers.
      Data were analyzed in SPSS-16 software and tested for association between atrial
      fibrillation with creatinine level by using student t test, chi-square test or
      logistic regression. Cr level in patients with and without AF three days before
      surgery were 1.8+/-0.3 and 1.0+/-0.4 respectively (P value for Cr=0.00). On
      surgical day, mean Cr level in patients with and without AF were 1.6+/-0.2 and
      1.1+/-0.5 respectively (P value for Cr = 0.00). Of the 100, male patients with
      postoperative AF, duration and frequency of recurrence of AF were not associated
      with Cr at three days before surgery and on surgical days (P>0.05). Patients with
      postoperative AF had unsuitable status of renal function compare to patients
      without AF; however, preoperative serum creatinine cannot associate with duration
      and frequency of recurrence of AF. 

PMID- 24442541
TI  - Chlamydia pneumoniae in the atherosclerotic plaques of coronary artery disease
      patients.
AB  - An association between Chlamydia pneumoniae (C. pneumoniae) and cardiovascular
      disease has been demonstrated. In this study, we aimed to study this potential
      relationship in 105 Iranian patients. Coronary artery specimens from 105 Iranian
      patients undergoing CABG were analyzed by PCR method for C. pneumoniae.
      Serological evaluation for C. pneumoniae IgG and IgM was performed using ELISA.
      53 specimens from mamillary artery were also investigated. C. pneumoniae PCR test
      result was positive for 23 (21.9%) of patients with coronary artery
      atherosclerosis, but none of the specimens from the mamillary artery was positive
      for C. pneumoniae when it was evaluated by the PCR (P<0.001). Coronary artery
      disease patients with and without a history of unstable angina or myocardial
      infarction were comparable in C. pneumoniae PCR test positive rates (P=0.618).
      Relevance of IgG and IgM positivity were also studied by correlating it to the
      study parameters, but no difference was found. CRP was significantly higher in
      the IgM positive group (P<0.001). A significant proportion of coronary
      atherosclerotic plaques are infected with C. pneumoniae while no infection was
      found in the normal mamillary artery specimens. No association was found between
      acute coronary syndromes and serological and PCR positivity. Further prospective
      randomized controlled studies with large patient population are needed to confirm
      our findings. 

PMID- 24442542
TI  - Antibiotics induced acute kidney injury: incidence, risk factors, onset time and
      outcome.
AB  - Drug induced acute kidney injury (AKI) has been implicated in 8% to 60% of all
      cases of in-hospital AKI and as such is a recognized source of significant
      morbidity and mortality. Evaluation of incidence, risk factors, onset time, and
      outcome of  antibiotics' associated acute kidney injury. During one-year period,
      all patients who developed acute kidney injury during their hospital stay in the
      infectious diseases ward of Imam Khomeini hospital were included in the study
      prospectively. Patients' demographic data, baseline diseases, cause of current
      hospital admission, history of past and current medications and hemodynamic
      parameters were collected and monitored closely. Drug induced acute kidney injury
      was defined based on acute kidney injury network criteria. From 424 admitted
      patients, 76 (17.9%) developed acute kidney injury. Aminoglycosides (gentamicin
      and amikacin), amphotericin B, vancomycin, beta-lactam antibiotics (cefazolin and
      ceftriaxone) in monotherapy and combination therapy were the causes of acute
      kidney injury in most of the patients. From the co-morbid diseases in patients
      with acute kidney injury, diabetes mellitus (26.3%) and hypertension (5.5%), were
      the most frequent ones. Presence of diabetes mellitus as comorbidity (OR=2.6;
      CI=1.3-5.7, P=0.01), dehydration of patients upon admission (OR=3.4; CI=1.9-6.4,
      P<0.001), and administration of nephrotoxic combinations (OR=2.1; CI=1.2-4.1,
      P=0.04) were independent risk factors for antibiotic induced nephrotoxicity in
      our study. About 18% of the patients developed acute kidney injury during their
      hospitalization period in the infectious diseases ward. Aminoglycosides,
      amphotericin B, vancomycin and beta-lactam antibiotics were responsible agents
      for acute kidney injury in this study. 

PMID- 24442543
TI  - Clinicopathological study of 1016 consecutive adnexal skin tumors.
AB  - Adnexal tumors (ATs) are primary skin tumors with benign or rarely, malignant
      behavior. They have been classified based on differentiation towards hair
      follicle, sebaceous, apocrine or eccrine gland. Few large-scale studies have
      focused on ATs. To determine the prevalence of ATs and to assess clinical and
      histopathological trend of ATs. A retrospective descriptive study of all ATs
      diagnosed in Razi hospital between 2006 and 2010 was performed. A total of 30,000
      pathology records were reviewed, and 1016 ATs were included. The prevalence of
      ATs was 3.3%. 518 patients (51%) were female, with a mean age of 34.5 years. 953
      tumors (93.8%) were benign. ATs were most commonly located in the head and neck
      area (822, 83.5%). The most common histopathological origin of ATs was sebaceous
      gland (536, 52.7%). Sebaceous nevus of Jadassohn was the most prevalent single
      tumor type (40.6% of all ATs). In 63.6% (646) of tumors, ATs were clinically
      suspected by the clinician prior to biopsy. The most common malignant AT was
      sebaceous carcinoma (23, 36.5% of all malignant ATs). ATs are infrequent lesions,
      most commonly occurring in 3rd and 4th decade of life. Diagnosis of ATs is made
      by histopathological studies as they often express indistinctive clinical
      features. Malignant ATs are rare, occur at an older age, and are often hard to
      recognize clinically. 

PMID- 24442544
TI  - Tinnitus: an epidemiologic study in Iranian population.
AB  - A wide range of population, 4% to 30%, suffers from tinnitus that is defined as
      perception of sound without apparent acoustic stimulus. We conducted the present
      study to determine the prevalence of tinnitus in Iranian population; Tehran
      province. This cross-sectional study was conducted from January 2009 to December
      2009, recruiting 3207 individuals (age range, 7-98) who were residing in Tehran
      province, Iran. Participants were asked to fill two questionnaires; the validated
      Persian version of Tinnitus Questionnaire (TQ) and another one that was
      specifically designed for this study. Prevalence of tinnitus and its association
      factors were evaluated. 3207 participants enrolled into our study comprising 1429
      (44.7%) male and 1765 (55.3%) female with mean age of 55.01+/-17.85. Of total of
      3207 participants, 146 (4.6%) had tinnitus consisting of 80 male (54.8%) and 66
      (45.2%) female participants. It showed a rising trend with increasing age that
      was especially significant after the sixth decade of life (P=0.001). The analysis
      showed mean TQ global score of 35.96+/-25.52 that was significantly different
      between male and female participants (P=0.051) and had no significant correlation
      with increasing age (Spearman's r=0.1, P=0.10). The tinnitus intensity was
      moderate to very severe in 95 (56.1%) of the participants. Its severity level was
      not significantly different between men and women (P=0.09). Tinnitus intensity
      had no significant association with increasing age (Spearman's r=0.1, P=0.31).
      Patients with higher TQ global score had higher tinnitus intensities (P=0.001).
      The annoyance level was significantly different between men and women (P=0.04)
      and its impact on the participants daily routine functions were significantly
      higher in men (P=0.003). Given the results of the study, demonstrating that
      prevalence of tinnitus in Iranian population (Tehran province) was lower than the
      other countries and had a direct correlation with increasing age only after the
      sixth decade. TQ global score had significant correlation with tinnitus
      intensity, annoyance and impact on the participants' daily routine functions.
      However, none of the above had correlation with increasing age. Tinnitus TQ
      global score and intensity were not different between men and women; however
      annoyance of tinnitus and its impact on participants' daily routine functions
      were significantly higher in men. 

PMID- 24442545
TI  - Helicobacter pylori seropositivity in patients with type 2 diabetes mellitus in
      south-east of Iran.
AB  - It has been also reported that that H. pylori infection may be responsible for
      some endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus
      and primary hyperparathyroidism. H. pylori which express cytotoxin-associated
      gene A (CagA) may be more virulent than those that do not. The aim was to
      evaluate the seroprevalence of anti-H. pylori IgG and anti-CagA  antibodies in
      patients with type 2 diabetes mellitus (type 2 DM) and healthy individuals from
      Rafsanjan city (Iran). A total of 100 patients with type 2 diabetes and 100 age
      matched healthy individuals were enrolled to study. A blood sample was collected
      from each participant. The type 2 DM established according to the fasting blood
      glucose level of 126 mg/dl. The sera were tested for the presence of anti-H.
      pylori IgG antibodies and antibody to CagA by use of enzyme linked immunosorbent
      assay. The seroprevalence of anti-H. pylori antibodies in diabetic  patients
      (76%) was similar to that observed in healthy subjects (75%). The mean titer of
      anti-H. pylori IgG in healthy control group (131.63+/-11.68 U/ml) was
      significantly higher than diabetic group (54.43+/-4.50 U/ml; P<0.0001). The
      prevalence of serum anti-CagA IgG antibodies was 78.9% in infected diabetic
      patients and 77.3% in healthy control group with mean titer of 75.02+/-4.54 U/ml
      and 84.34+/-5.85 U/ml, respectively. No significant differences were observed
      between diabetic and healthy control groups regarding the prevalence and the mean
      titer of anti-CagA IgG antibodies. In the diabetic group, the seropositive rate
      of anti-H. pylori IgG was higher in women as compared to men, but the difference
      was not statistically significant. These results show that H. pylori
      seropositivity rate was similar in type 2 DM patients and non-diabetics control
      group. No association was also found between CagA-positive strains of H. pylori
      and type 2 DM. 

PMID- 24442546
TI  - Medical student's benefit rates from the clinical teaching rounds and its
      associated factors in Tehran University of Medical Sciences in the year 2010.
AB  - Among the various methods of clinical teaching, rounds and grand rounds are
      considered as the gold standards. Clinical round includes some standard
      components and it plays an effective role in student's learning process. The aim
      of this study was to evaluate the content of teaching rounds in 40 clinical wards
      in 4 medical teaching hospitals affiliated to Tehran University of Medical
      Sciences in Tehran, Iran, and also to assess the learners benefit rate from these
      programs and determine the factors affecting those. This is a cross sectional,
      descriptive and analytical study conducted on 318 medical learners in different
      grades, about the content of clinical rounds. The data collection tool was a
      questionnaire made by researchers. The validity of the questionnaire according to
      experts opinions and the reliability with a pilot study conducted on 30 cases
      were confirmed (alpha=0.826). Data entered into the SPSS software and for
      analysis Chi-square, Student's t-test, ANOVA and linear regression analysis tests
      were used. In this study 20 subjects related to clinical rounds content were
      assessed. The highest score was related to the subject of diagnosis and the
      lowest one was related to legal issues. Overall, the mean score of the learner's
      benefit rate to this method was 3.52 out of five. The level of learner's benefit
      rate was above the average and the benefit rates according to educational grade,
      number of the students and faculties were significantly different (P<0.05).
      Average of the benefit rate among residents were significantly higher than the
      other medical trainees (P<0.05). In conclusion, in understudied clinical rounds,
      there has been more emphasized on history taking, clinical examinations and
      diagnosis subjects, and Issues like: accountability, health economy, patient's
      nutrition, non-drug treatments and medical legal issues are less considered in
      the studied rounds. 

PMID- 24442547
TI  - Spontaneous nystagmus in benign paroxysmal positional vertigo: is it a new sign?
AB  - Benign Paroxysmal Positional Vertigo (BPPV) is a condition that indicates a
      benign inner ear disorder. It is generally believed that BPPV is due to the
      dislodged otoconial particles from otolith organs and unusual collection of them
      within any of semicircular canals or even in all three semicircular canals.
      Although the typical features of nystagmus in BPPV have been well-studied, very
      few studies (just four articles) have highlighted the presence of spontaneous
      nystagmus in BPPV recently. During the past 10 years, 2850 patients have been
      examined at the audiology unit of our department, and 254 patients have received
      diagnoses of BPPV but recently 2 patients presented with BPPV and spontaneous
      nystagmus, a new symptom that has been never observed in our clinical records. We
      herein describe this rare symptom in 2 case of BPPV. A 50-year-old woman with
      BPPV who showed an 18 degree spontaneous nystagmus treated with Epley maneuver
      and a 53-year-old man with 3 degree spontaneous nystagmus. 

PMID- 24442548
TI  - Fraccaro syndrome: report of two Iranian cases: an infant and an adult in a
      family.
AB  - 49,XXXXY is rare chromosomal pattern and these patients have mental retardation,
      small penis, cryptorchidism and skeletal anomalies. We reported a 10 month-old
      boy who has hypotonia, microcephaly, hypertelorism, depressed nasal bridge,
      epicanthic folds and bilateral multiple ear tags, high arched palate, down set
      ears, micrognathia and congenital heart disease such as patent ductus arteriosus
      (PDA), Atrial septal defect (ASD), mild pulmonary stenosis. Among the skeletal
      anomalies, he has kyphoscoliosis, clinodactyly of the fourth and fifth fingers of
      both hands, and bilateral club foot and unilateral dysplasia of the hip.
      Karyotype was found as 49,XXXXY[44]/48,XXXY[6] and this cytogenetic analysis was
      help to establish clinical diagnosis Fraccaro syndrome.

PMID- 24442549
TI  - Acute cholangitis due to anomaly of right hepatic artery.
AB  - Acute cholangitis (AC) is commonly observed in general practice with different
      causes. We report a case of recurrent AC caused by anomaly of the right hepatic
      artery, as a rare underlying condition. 

PMID- 24442550
TI  - Metabolism changes during aging in the hippocampus and striatum of glud1
      (glutamate dehydrogenase 1) transgenic mice.
AB  - The decline in neuronal function during aging may result from increases in
      extracellular glutamate (Glu), Glu-induced neurotoxicity, and altered
      mitochondrial metabolism. To study metabolic responses to persistently high
      levels of Glu at synapses during aging, we used transgenic (Tg) mice that over
      express the enzyme Glu dehydrogenase (GDH) in brain neurons and release excess
      Glu in synapses. Mitochondrial GDH is important in amino acid and carbohydrate
      metabolism and in anaplerotic reactions. We monitored changes in nineteen
      neurochemicals in the hippocampus and striatum of adult, middle aged, and aged Tg
      and wild type (wt) mice, in vivo, using proton ((1)H) magnetic resonance
      spectroscopy. Significant differences between adult Tg and wt were higher Glu, N
      acetyl aspartate (NAA), and NAA + NAA-Glu (NAAG) levels, and lower lactate in the
      Tg hippocampus and striatum than those of wt. During aging, consistent changes in
      Tg and wt hippocampus and striatum included increases in myo-inositol and NAAG.
      The levels of glutamine (Gln), a key neurochemical in the Gln-Glu cycle between
      neurons and astroglia, increased during aging in both the striatum and
      hippocampus of Tg mice, but only in the striatum of the wt mice. Age-related
      increases of Glu were observed only in the striatum of the Tg mice. 

PMID- 24442551
TI  - Retro-cue benefits in working memory without sustained focal attention.
AB  - In working memory (WM) tasks, performance can be boosted by directing attention
      to one memory object: When a retro-cue in the retention interval indicates which
      object will be tested, responding is faster and more accurate (the retro-cue
      benefit). We tested whether the retro-cue benefit in WM depends on sustained
      attention to the cued object by inserting an attention-demanding interruption
      task between the retro-cue and the memory test. In the first experiment, the
      interruption task required participants to shift their visual attention away from
      the cued representation and to a visual classification task on colors. In the
      second and third experiments, the interruption task required participants to
      shift their focal attention within WM: Attention was directed away from the cued
      representation by probing another representation from the memory array prior to
      probing the cued object. The retro-cue benefit was not attenuated by shifts of
      perceptual attention or by shifts of attention within WM. We concluded that
      sustained attention is not needed to maintain the cued representation in a state
      of heightened accessibility. 

PMID- 24442552
TI  - [Ridge preservation with synthetic nanocrystalline hydroxyapatite reduces the
      severity of gingival invaginations-a prospective clinical study].
AB  - BACKGROUND AND OBJECTIVE: Gingival invaginations develop after tooth extraction
      and subsequent orthodontic space closure. Aetiological factors and long-term
      effects of gingival invaginations on oral health are nearly unknown. In addition,
      preventive or therapeutic strategies are rare. This prospective clinical study
      employing the split mouth technique was performed to investigate the effect of
      extraction socket augmentation with a synthetic nanocrystalline hydroxyapatite
      (NanoBone((r)) Artoss, Rostock, Germany) on the incidence and degree of gingival
      invaginations. MATERIAL AND METHODS: A total of 10 orthodontic patients with need
      for symmetric premolar extractions offering a total of 28 extractions were
      included in this trial. The study plan provided one extraction site to be
      augmented with synthetic nanocrystalline hydroxyapatite (NanoBone((r))), the
      other served as control. After primary wound healing, space closure was performed
      under defined biomechanical conditions. After space closure was accomplished,
      occurrence and degree of gingival invaginations as well as probing depths of the
      adjacent teeth mesial and distal to the extractions were determined and dental
      radiographs were taken. RESULTS: The degree of gingival invaginations and probing
      depths mesial and distal of the extraction were significantly reduced on
      NanoBone((r)) augmented extraction sites. In addition, 70% of the radiographs
      revealed translucent and hyperdense areas on the intervention side after space
      closure. Apical root resorption was found in 2 patients on both the NanoBone((r))
      side and the control side. CONCLUSION: Ridge preservation with NanoBone((r))
      appeared to reduce the severity of gingival invaginations. Further investigation
      on long-term effects is mandatory to eliminate the appearance of adverse effects.

PMID- 24442553
TI  - Upper molar distalization with skeletally anchored TopJet appliance.
AB  - OBJECTIVE: To retrospectively investigate clinical outcomes with the TopJet
      appliance. MATERIALS AND METHODS: Measurements were taken on dental casts
      reflecting situations in 15 patients aged 10-48 years before and after
      orthodontic treatment with a TopJet appliance. Each measurement was taken with a
      digital caliper and repeated 2 weeks later. Recorded parameters included the
      amounts of distalization achieved, durations of active treatment to calculate
      rates of tooth movement, as well as rotational and transversal changes involved
      in the distalization of upper first molars. Student's t-test was used to compare
      mean values (alpha=0.05), explorative analysis to distinguish between unilateral
      and bilateral use of TopJet appliances, and Pearsons's correlation coefficient to
      determine intraobserver variability. RESULTS: Over a mean treatment duration of
      5.9 months, the upper first molars were distalized by 4.0 +/- 2.2 mm, including a
      mean tooth movement rate of 0.8 +/- 0.6 mm per month. The rotational changes
      involved in the movements (-1.4 +/- 6.7 degrees ) were not statistically
      significant. Transversal changes were 0.9 +/- 1.2 mm at the level of the
      mesiobuccal cusps, 1.1 +/- 1.1 mm at the central fossae, and 0.9 +/- 0.9 mm at
      the distobuccal cusps. All measurements, other than those for rotation (r=0.7),
      were highly reproducible. Bilateral use of the appliance resulted in greater
      distalization than unilateral use, the mean difference being 1.4 mm. Bilateral
      use was more likely to involve inward rotation (+2.0 degrees ) on the mesial
      aspect of the first molars, whereas unilateral use resulted in mild outward
      rotation (-0.5 degrees ). CONCLUSION: Our results indicate that upper molars can
      be distalized effectively and efficiently with TopJet appliances. Any degrees of
      rotation and transversal changes that the first molars undergo during this
      process do not seem to play a major role.

PMID- 24442554
TI  - Effects of a hinged expansion screw for median mandibular distraction treatment
      on the lower first molars regarding tooth inclination and intermolar transverse
      distance.
AB  - OBJECTIVES: The goal of this study was to assess the extent to which median
      mandibular distraction via a cemented and screw-retained full-coverage splint
      appliance employing a hinged expansion screw causes inclination changes in the
      lower first molars and widens the dental arch. METHODS: Our study included 17
      patients (12 females and 5 males; average age 16 years and 3 months) who
      presented with transverse space deficits and pronounced dental crowding. Baseline
      and final mandibular casts reflecting the situations before and after 6 weeks of
      median distraction therapy were created, scanned, and matched via their
      coordinate systems. Perpendiculars were drawn at the geometric centers between
      the cusp tips of teeth 36 and 46 and projected against the frontal plane. The
      intersection angles yielded single-tooth and total inclination values for both
      molars, and the difference between the intermolar distances measured at the
      geometric centers of both teeth provided the amount of transverse expansion.
      RESULTS: An intraclass correlation coefficient (ICC) of >0.99 was obtained in a
      series of three measurements. After distraction treatment, the total inclination
      values between teeth 36 and 46 changed by +2.93 +/- 9.14 degrees . The
      corresponding single-tooth inclinations changed by +0.68 +/- 6.32 degrees  and 
      2.25 +/- 4.33 degrees , respectively. Both molars underwent similar degrees of
      buccal or lingual tipping. Compared to a mean expansion of +6.9 +/- 1.83 mm at
      the distraction screw, a distance increase of only +3.77 +/- 1.27 mm along the
      transversal connecting teeth 36 and 46 was recorded. Pearson's correlation
      coefficient was 0.336 between total tipping and intermolar expansion (p=0.187)
      and -0.426 between total tipping and patient age (p=0.088). CONCLUSION: Expansion
      amounts were approximately twice as long at the expansion screw as between the
      first molars. This V-shaped expansion pattern was due to the hinged connections
      between each expansion screw and the full-coverage splints. The buccal and
      lingual tipping of molars measured may be due to varying heights of the posterior
      alveolar ridge during mixed dentition or to anatomy-related differences in the
      expansion-screw position. In all cases we observed a mainly parallel opening of
      the distraction gap on the vertical plane.

PMID- 24442555
TI  - Prevalence of class III malocclusion and crossbite among children and adolescents
      with craniomandibular dysfunction.
AB  - Numerous studies have been devoted to the causes of craniomandibular dysfunction
      (CMD). This investigation addressed the effect of class III malocclusion and
      crossbite on CMD based on a sample of 115 prepubertal and adolescent patients of
      both sexes. Although class III malocclusion only accounted for 12.2% of the total
      sample, thus, being the smallest group, the percentage of crossbite (71.4%) among
      these patients was disproportionately higher than among the other classes. Of the
      total sample, the prevalence of crossbite was 30.4%. We compared these findings
      to a large-scale (n=4727) study by Thilander et al. (2002), who reported a
      strikingly high percentage of class I patients compared to our findings (72.7%
      versus 27.8%) and a lower percentage of crossbite cases (8.0% versus 30.4%). In
      accordance with the "orthodontic risk child" concept by Grabowski et al. (2007)
      and Stahl et al. (2007), we conclude that class III malocclusion and crossbite
      are keys in the pathogenesis of CMD.

PMID- 24442556
TI  - Electrophysiological method to examine muscle fiber architecture in the upper lip
      in cleft-lip patients.
AB  - OBJECTIVES: The upper lip's musculature comprises several muscle fiber groups
      with different spatial orientations for various lip movements. In the past, it
      has not been possible to describe these various groups and their motor units in
      detail with traditional methods of electromyography (EMG). The purpose of this
      investigation was to create a viable method for studying the architecture of
      upper-lip muscle fibers in patients with surgically closed cleft lip by refining
      the design of a flexible electrode array for multichannel EMG. METHODS:
      Calibrated perioral photographs of 36 adult subjects were used to determine the
      basic geometry of an electrode array for use on different facial shapes. A total
      of 256 chloride silver electrodes, 1 mm in diameter, were distributed over this
      geometry to form a grid with interelectrode distances of 2.5 mm. Technical
      implementation of the electrode array was based on a modified technique used for
      flexible printed circuit boards. A double-sided adhesive tape with perforations
      was used to apply the array to the skin in the upper-lip area. Surface EMG
      signals were recorded while the subjects were performing various lip movements
      and exerting specific lip forces. The latter were recorded with a specially
      developed transducer. RESULTS: Despite an extremely dense grid of electrodes
      associated with downsized contacts, the electrode array could be precisely
      applied to the perforated adhesive tape. The electrode array remained firmly
      attached to the skin even during extensive lip movements. The recorded EMG
      signals offered high baseline stability and a strong signal-to-noise ratio, thus,
      allowing us to extract individual motor unit action potentials (MUAPs).
      Spatiotemporal tracking of MUAPs succeeded in demonstrating the course of muscle
      fibers belonging to individual motor units. Pilot measurements taken on subjects
      with surgically closed unilateral cleft lip revealed an asymmetric distribution
      of muscle activity surrounding the closed cleft-lip segments. CONCLUSION: Our
      refined noninvasive electrophysiological method is capable of providing detailed
      information about muscle fiber architecture and the position, size, and
      organization of motor units in the lip area. It is thus feasible to conduct
      further studies to analyze differences in muscle morphology and motor control
      between surgically treated cleft-lip patients and noncleft individuals.

PMID- 24442557
TI  - Emotion recognition from facial expressions: a normative study of the Ekman 60
      Faces Test in the Italian population.
AB  - The Ekman 60-Faces (EK-60F) Test is a well-known neuropsychological tool
      assessing emotion recognition from facial expressions. It is the most employed
      task for research purposes in psychiatric and neurological disorders, including
      neurodegenerative diseases, such as the behavioral variant of Frontotemporal
      Dementia (bvFTD). Despite its remarkable usefulness in the social cognition
      research field, to date, there are still no normative data for the Italian
      population, thus limiting its application in a clinical context. In this study,
      we report procedures and normative data for the Italian version of the test. A
      hundred and thirty-two healthy Italian participants aged between 20 and 79 years
      with at least 5 years of education were recruited on a voluntary basis. They were
      administered the EK-60F Test from the Ekman and Friesen series of Pictures of
      Facial Affect after a preliminary semantic recognition test of the six basic
      emotions (i.e., anger, fear, sadness, happiness, disgust, surprise). Data were
      analyzed according to the Capitani procedure [1]. The regression analysis
      revealed significant effects of demographic variables, with younger, more
      educated, female subjects showing higher scores. Normative data were then applied
      to a sample of 15 bvFTD patients which showed global impaired performance in the
      task, consistently with the clinical condition. We provided EK-60F Test normative
      data for the Italian population allowing the investigation of global emotion
      recognition ability as well as selective impairment of basic emotions
      recognition, both for clinical and research purposes.

PMID- 24442559
TI  - How we see ourselves: a resident's reflection on the class play.
AB  - The "class play" is an annual tradition in residency training programs and
      medical schools that celebrates the end of the academic year. It is also a
      locally generated narrative that reveals important components of an institution's
      values, culture, and group dynamics. Exploring the class play is a reflexive
      exercise that allows one to reflect on his or her professional development and
      place in the department in a structural, historical, and experience-near driven
      way. In this way, the creation of and examining of the class play may be seen as
      an opportunity to understand and expand upon medicine's Hidden Curriculum. 

PMID- 24442560
TI  - Consistent and significant improvement of nighttime voiding frequency (nocturia)
      with silodosin in men with LUTS suggestive of BPH: pooled analysis of three
      randomized, placebo-controlled, double-blind phase III studies.
AB  - OBJECTIVES: Nocturia is prevalent and bothersome in men with lower urinary tract
      symptoms suggestive of BPH (LUTS/BPH). alpha-Adrenoceptor antagonists without
      subtype selectivity have inconsistently shown significant effects on nocturia in
      these patients. We explored the effects of the alpha1A-adrenoceptor subtype
      selective antagonist silodosin on nocturia by analyzing three placebo-controlled
      registration studies. METHODS: Responses to question 7 of the IPSS questionnaire
      were analyzed for the entire study population and patients with >= 2 voids/night
      at baseline. Improvement/worsening rates for nocturia were calculated for once
      daily silodosin 8 mg and placebo. Silodosin effects on the mean number of
      nocturnal voids were compared with placebo, and the number of patients in whom
      nocturia was reduced to <2 times was calculated. RESULTS: In total, 1,479 men
      were treated with silodosin or placebo; 1,266 men (85 %) had >= 2 voids/night at
      baseline. Compared to placebo, more men treated with silodosin reported about
      nocturia improvement (53.4 vs. 42.8 %, p < 0.0001) and fewer patients about
      worsening (9.0 vs. 14.3 %, p < 0.0001). Silodosin significantly reduced nocturia
      within each study and pooled cohort compared to placebo (p < 0.001). In men with
      >= 2 nocturnal voids at baseline, 61 and 49 % of patients with silodosin and
      placebo had reductions of >= 1 voids/night, respectively (p = 0.0003), and
      significantly more patients with silodosin had <2 nocturia episodes at study end
      compared to placebo (29.3 vs. 19.0 %; p = 0.0002). CONCLUSIONS: Although a weak
      impact on nocturia is already known from alpha-adrenoceptor antagonists without
      subtype selectivity, the individual placebo-controlled studies and the pooled
      data analysis showed that the alpha1A-adrenoceptor subtype-selective antagonist
      silodosin consistently and significantly improves nocturia in men with LUTS/BPH.

PMID- 24442561
TI  - The quantification of glenoid bone loss in anterior shoulder instability; MR
      arthro compared to 3D-CT.
AB  - OBJECTIVE: The purpose of this study is to investigate if magnetic resonance
      imaging with intra-articular contrast (MR-arthro) is as reliable as three
      dimensionally reconstructed computed tomography imaging (3D-CT) in quantifying
      the glenoid bone loss in patients with anterior shoulder instability. MATERIALS
      AND METHODS: Thirty-five patients were included. Sagittal MR-arthro and 3D-CT
      images of the glenoid surface were obtained pre-operatively. Two observers
      measured these images twice with OsiriX software in a randomized and blinded way.
      The intraclass correlations (ICC) of the intra- and inter-observer reliability
      within one method and an additional Bland-Altman plot for calculating agreement
      between the two methods were obtained. RESULTS: The joint estimates of the intra
      observer reliability, taking into account the data from both observer A and B,
      for 3D-CT and MR-arthro were good to excellent. The intra-observer reliability
      was 0.938 (95% CI: 0.879, 0.968) for 3D-CT and 0.799 (95% CI: 0.639, 0.837) for
      MR-arthro. The inter-observer reliability between the two observers within one
      method (3D-CT or MR-arthro) was moderate to good. 3D-CT: 0.724 (95% CI: 0.236,
      0.886) and MR-arthro: 0.534 (95% CI: 0.128, 0.762). Comparing both the 3D-CT and
      MR-arthro method, a Bland-Altman plot showed satisfying differences with the
      majority of outcomes (89%) within 1 SD. CONCLUSIONS: Good to excellent intra- and
      moderate to good inter-observer correlations and a satisfying Bland-Altman plot
      when compared to 3D-CT show tendencies that MR-arthro is reliable and valid for
      measuring bony defects of the glenoid.

PMID- 24442562
TI  - Radiographic classification for fractures of the fifth metatarsal base.
AB  - OBJECTIVE: Avulsion fractures of the fifth metatarsal base (MTB5) are common fore
      foot injuries. Based on a radiomorphometric analysis reflecting the risk for a
      secondary displacement, a new classification was developed. MATERIALS AND
      METHODS: A cohort of 95 healthy, sportive, and young patients (age <= 50 years)
      with avulsion fractures of the MTB5 was included in the study and divided into
      groups with non-displaced, primary-displaced, and secondary-displaced fractures.
      Radiomorphometric data obtained using standard oblique and dorso-plantar views
      were analyzed in association with secondary displacement. Based on this, a
      classification was developed and checked for reproducibility. RESULTS: Fractures
      with a longer distance between the lateral edge of the styloid process and the
      lateral fracture step-off and fractures with a more medial joint entry of the
      fracture line at the MTB5 are at higher risk to displace secondarily. Based on
      these findings, all fractures were divided into three types: type I with a
      fracture entry in the lateral third; type II in the middle third; and type III in
      the medial third of the MTB5. Additionally, the three types were subdivided into
      an A-type with a fracture displacement <2 mm and a B-type with a fracture
      displacement >= 2 mm. A substantial level of interobserver agreement was found in
      the assignment of all 95 fractures to the six fracture types (kappa = 0.72). The
      secondary displacement of fractures was confirmed by all examiners in 100%.
      CONCLUSIONS: Radiomorphometric data may identify fractures at risk for secondary
      displacement of the MTB5. Based on this, a reliable classification was developed.

PMID- 24442563
TI  - Localization of the C4 and C 3 pathways of photosynthesis in the leaves of
      Pennisetum purpureum and other C4 species. Insignificance of phenol oxidase.
AB  - Mesophyll protoplasts and bundle-sheath cells of Pennisetum purpureum Schum., a
      C4 plant with low phenol-oxidase activity, were enzymatically separated according
      to methods recently developed with sugarcane (Saccharum officinarum L.), maize
      (Zea mays L.), and sorghum (Sorghum bicolor L.). The phosphoenolpyruvate
      carboxylase and NADP-malic dehydrogenase of the C4 pathway were found to be
      localized in the mesophyll protoplasts while ribulose-1,5-diphosphate (RuDP)
      carboxylase, phosphoribulokinase and NADP-malic enzyme were localized in the
      bundle-sheath cells. The levels of these enzyme activities in the leaf extracts
      and in certain cellular preparations of P. purpureum are sufficient to account
      for the rate of photosynthesis in the leaf. These results on the activities and
      distribution of photosynthetic enzymes with P. purpureum preparations are
      consistent with our previous evidence for cellular separation of the C4 and the
      reductive pentose-phosphate pathways in C4 species.With chlorogenic acid as the
      substrate, P. purpureum, Setaria lutescens (Weigel) Hubb. and Panicum texanum
      Buckl. have relatively low phenol-oxidase activity, similar to that found in
      spinach (Spinacia oleracea L.); while sorghum, sugarcane, maize, Panicum
      capillare L. and P. miliaceum L. have relatively high phenoloxidase activity,
      similar to that in tobacco (Nicotiana tabacum L.). C4 species having high phenol
      oxidase activity have substantial activity of the enzyme in both mesophyll and
      bundle-sheath extracts. Since phenol oxidase is found in both cell types it is
      not logical to expect preferential inhibition of RuDP carboxylase or other
      photosynthetic enzymes through phenol oxidation in mesophyll extracts, as has
      been previously suggested. When dithiothreitol and polyvinylpyrrolidone were
      included in the enzyme extraction medium, the activity of RuDP carboxylase
      increased 10% in P. purpureum and 59% in sugarcane leaf extracts. 

PMID- 24442564
TI  - Biochemical and cytological relationships in C4 plants.
AB  - C4 plants can be divided into three groups based on differences in activities of
      three decarboxylating enzymes: NADP-malic enzyme, NAD-malic enzyme, and
      phosphopyruvate carboxykinase.In the Gramineae the three C4 groups are
      distinguished by anatomical and ultrastructural characteristics of bundle-sheath
      chloroplasts. NADP-malic enzyme species lack well-developed grana in bundle
      sheath chloroplasts (grana reduced) and the bundle-sheath chloroplasts are in the
      centrifugal position. NAD-malic enzyme species have bundle-sheath chloroplasts in
      the centripetal position and contain grana. Phosphopyruvate carboxykinase species
      have bundle-sheath chloroplasts in the centrifugal position and they contain
      grana. NADP-malic enzyme species of the Gramineae have only been found in the
      subfamilies Aristidoideae and Panicoideae. With the exception of the genera
      Panicum, and Urochloa, NAD-malic enzyme species and phosphopyruvate carboxykinase
      species have only been found in the subfamily Eragrostoideae. C4 species of the
      genus Panicum are found among all three of the C4 groups.The dicotyledonous C4
      species examined fall into two groups: those having high NADP-malic enzyme and
      those having high NAD-malic enzyme. No phosphopyruvate carboxykinase C4 species
      have been found among the dicotyledons. The NADP-malic enzyme C4 species of the
      dicotyledons like NADP-malic enzyme species of the Gramineae have bundle-sheath
      chloroplasts with reduced grana but in contrast to NADP-malic enzyme species of
      the Gramineae the bundle-sheath chloroplasts are in the centripetal position. The
      NAD-malic enzyme species of the dicotyledons like the NAD-malic enzyme species of
      the Gramineae have bundlesheath chloroplasts in the centripetal position with
      well developed grana.The results are discussed in terms of evolutionary and
      functional diversification of C4 plants. 

PMID- 24442565
TI  - Sieve-element ultrastructure in Platycerium bifurcatum and some other
      polypodiaceous ferns: The nucleus.
AB  - Sieve elements of various ages were examined in Platycerium bifurcatum (Cav.) C.
      Chr. and Phlebodium aureum (L.) J. Sm., only older ones in Polypodium schraderi
      Mett. and Microgramma lycopodioides (L.) Copel. Early in sieve-element
      differentiation small crystalloids arise in the matrix of the sieve-element
      nuclei in Platycerium. As differentiation continues, the crystalloids increase in
      size and eventually may occupy up to a third of the cross-sectional area of the
      nucleus and extend almost its entire length. At the time of nuclear degeneration
      the crystalloids are liberated into the cytoplasm. Nuclear degeneration during
      sieve-element development in Phlebodium is essentially similar to that in
      Platycerium, with the exception that no nuclear inclusions exist in the sieve
      element nuclei in Phlebodium. Stacking of endoplasmic reticulum against the
      nuclear envelope occurs in both Platycerium and Phlebodium. In the final stages
      of degeneration, the nuclear envelope ruptures and the contents of the nucleus
      mix with the cytoplasm. At maturity the sieve elements of all four species are
      devoid of nuclei, although occasional remnants of chromatin persist along the
      walls of some mature cells. 

PMID- 24442566
TI  - Sieve-element ultrastructure in Platycerium bifurcatum and some other
      polypodiaceous ferns: The refractive spherules.
AB  - Sieve elements of various ages of Platycerium bifurcatum (Cav.) C. Chr. and
      Phlebodium aureum (L.) J. Sm. and older ones of Polypodium schraderi Mett. and
      Microgramma lycopodioides (L.) Copel. were examined with the electron microscope.
      Evidence was obtained which implicated the Golgi apparatus with the formation of
      refractive spherules in Platycerium and Phlebodium. In all four species the
      delimiting membranes of the refractive spherules eventually fuse with the
      plasmalemma in mature sieve elements, and the material comprising the spherules
      is liberated into the region of the wall. 

PMID- 24442567
TI  - Interrelationship between nitrate assimilation and carbohydrate metabolism in
      plant roots.
AB  - The effect of nitrate incubation on the pattern of carbohydrate metabolism in
      different regions of the pea (Pisum sativum L. var. Kelvedon Wonder) root has
      been studied. Roots were incubated in a 10 mM potassium nitrate solution for 4, 8
      and 12 h. Marked increases were noted in the activities of nitrate assimilation
      enzymes after 4 h. Increased activities were also recorded for hexokinase,
      pyruvate kinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate
      dehydrogenase and transketolase. No consistent changes were observed in the
      activities of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase.
      Experiments with [1-(14)C] and [6-(14)C]glucose indicated a relative shift in the
      pattern of carbohydrate oxidation from glycolysis to the pentose phosphate
      pathway. The data are interpreted as indicating a close interrelationship between
      nitrate assimilation and carbohydrate metabolism, particularly in relation to the
      supply of NADPH by the pentose phosphate pathway for nitrite reductase. 

PMID- 24442568
TI  - Measurement of oxygen partial pressure within soybean nodules by oxygen
      microelectrodes.
AB  - The internal pO2 of soybean (Glycine max Merr.) nodules was measured with oxygen
      microelectrodes. For nodules in air at 23 degrees , the pO2 decreased sharply
      across the nodule cortex, and was too low to measure in the central tissue. At 1
      degrees  in 1.0 atm O2, the pO2 in the central tissue was measurable, and was
      approximately uniform from the center to the edge of the central tissue. This
      uniformity was probably due to the intercellular air spaces of the central
      tissue, since infiltrating the spaces with water substantially decreased the pO2
      in the central tissue. The results strongly suggest that most of the resistance
      to O2 diffusion into the nodule occurs within the cortex. 

PMID- 24442569
TI  - Microfilaments and microtubules in elongating parenchyma cells of Nymphoides
      indica.
AB  - Observations on microfilaments and microtubules in elongating parenchyma cells of
      the central vascular bundle of Nymphoides indica (L.) O. Kuntze petiole are
      reported and discussed in relation to current concepts of the involvement of
      cellular organelles in cell wall synthesis. 

PMID- 24442570
TI  - Redo Ileal pouch-anal anastomosis combined with anti-TNF-alpha maintenance
      therapy for Crohn's disease with pelvic fistula: report of two cases.
AB  - Pouch failure has been reported to occur after ileal pouch-anal anastomosis for
      Crohn's disease. We report two cases of patients with Crohn's disease, who
      underwent redo ileal pouch-anal anastomosis (redo-IPAA) combined with anti-TNF
      alpha maintenance therapy, with good functional results. The first patient, a man
      with presumed ulcerative colitis, suffered pelvic fistula recurrence and
      anastomotic dehiscence. He underwent redo-IPAA, at which time longitudinal ulcers
      were found. Infliximab was started 4 days postoperatively and continued. The
      second patient, a woman treated for ulcerative colitis, underwent laparoscopic
      IPAA 8 years later. After the development of a pelvic fistula, twisted mesentery
      of the ileal pouch was found intraoperatively and Crohn's disease was diagnosed.
      Adalimumab therapy resulted in fistula closure. Redo-IPAA was performed to
      normalize the twisted mesentery of the ileal pouch. No complications have been
      observed in either patient, both of whom have experienced good functional results
      after closure of the covering stomas.

PMID- 24442571
TI  - Gold complexes with benzimidazole derivatives: synthesis, characterization and
      biological studies.
AB  - Synthesis, characterization, DFT studies and biological assays of new gold(I) and
      gold(III) complexes of benzimidazole are reported. Molecular and structural
      characterizations of the compounds were based on elemental (C, H and N) and
      thermal (TG-DTA) analyses, and FT-IR and UV-Visible spectroscopic measurements.
      The structures of complexes were proposed based DFT calculations. The
      benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested
      against three Leishmania species related to cutaneous manifestations of
      leishmaniasis. The free benzimidazole compounds showed no leishmanicidal
      activity. On the other hand, the gold(I and III) complexes have shown to possess
      significant activity against Leishmania in both stages of parasite, and the
      gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with
      IC50 values below 5.7 MUM. Also, the gold complexes showed high leishmania
      selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more
      toxic for the parasite than for macrophages. Besides the leishmanicidal activity,
      all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer
      cells. 

PMID- 24442572
TI  - The application of Oncotype DX in early-stage lymph-node-positive disease.
AB  - The recurrence score derived from the 21-gene Oncotype DX assay is both
      prognostic and predictive of adjuvant chemotherapy benefit in node-negative,
      estrogen-receptor-positive breast cancer patients treated with tamoxifen. This
      has led to a remarkable shift in the treatment paradigm, with a sizeable number
      of patients being able to avoid adjuvant chemotherapy. The recurrence score was
      then analyzed in a large retrospective study with node-positive, estrogen
      receptor-positive patients, in which it demonstrated both prognostic and
      predictive abilities. This review introduces the clinical trials that validated
      the Oncotype DX assay in the node-negative population, highlights the studies
      evaluating the utility of the assay in node-positive patients, examines the
      impact of the assay results on treatment decisions, and discusses the health
      outcomes and health care expenditures associated with this assay. 

PMID- 24442573
TI  - A serological survey for antibodies against foot-and-mouth disease virus (FMDV)
      in domestic pigs during outbreaks in Kenya.
AB  - Foot-and-mouth disease (FMD) is endemic in Kenya and has been well studied in
      cattle, but not in pigs, yet the role of pigs is recognised in FMD-free areas.
      This study investigated the presence of antibodies against FMD virus (FMDV) in
      pigs sampled during a countrywide random survey for FMD in cattle coinciding with
      SAT 1 FMDV outbreaks in cattle. A total of 191 serum samples were collected from
      clinically healthy pigs in 17 districts. Forty-two of the 191 sera were from pigs
      vaccinated against serotypes O/A/SAT 2 FMDV. Antibodies against FMDV non
      structural proteins were found in sera from 30 vaccinated and 71 non-vaccinated
      pigs, altogether 101/191 sera (53 %), and 91 % of these (92/101) also had
      antibodies measurable by serotype-specific ELISAs, predominantly directed against
      SAT 1 with titres of 10-320. However, only five high titres against SAT 1 in
      vaccinated pigs were confirmed by virus neutralisation test (VNT). Due to high
      degree of agreement between the two ELISAs, it was concluded that positive pigs
      had been infected with FMDV. Implications of these results for the role of pigs
      in the epidemiology of FMD in Kenya are discussed, and in-depth studies are
      recommended. 

PMID- 24442574
TI  - Abdominal wall mass and hemoabdomen in a Haflinger mare.
AB  - A 6-year-old Haflinger mare was presented with a history of recurrent
      hemoabdomen. On necropsy, a firm infiltrative multinodular yellow mass was
      observed in the wall of the posterior abdomen. Histopathologic examination
      revealed a proliferation of fibroblastic cells, which were positive for alpha
      smooth muscle actin and vimentin. 

PMID- 24442575
TI  - Toxic smoke inhalation in fire victim dogs.
AB  - Fifteen dogs were found dead in a house that was on fire. Several of these dogs
      were partially burned. Four dogs were submitted for postmortem examination, 2 of
      which were determined to have died prior to the fire. Of the 2 submitted fire
      fatalities, only 1 dog had burns on its body (dorsum and right side of body).
      Internally, both dogs had soot deposits mixed with mucus in the larynx, trachea,
      and primary bronchi. Microscopically, soot was identified within both airways and
      alveolar spaces. There were no macroscopic or microscopic indications of vital
      heat exposure. High levels of carboxyhemoglobin were detected in the 2 dogs
      tested. The findings in this case support the use of postmortem examination and
      toxicology testing to allow for determination of vital reaction to heat and fire
      fumes. 

PMID- 24442576
TI  - A brief overview of the 32nd Annual STP Symposium on the Toxicologic Pathology of
      the Digestive Tract and Pancreas.

PMID- 24442577
TI  - Quantitative determination of minerals and anthropogenic particles in some Polish
      peat occurrences using a novel SEM point-counting method.
AB  - A method is proposed for determining the mineral composition of peat using
      scanning electron microscope. In an illustrative example, five groups of
      particles occurring in amounts of >0.05% are distinguished in peat from Puscizna
      Mala bog in the Carpathian foreland, Poland. These are spheroidal aluminosilicate
      particles (SAP), feldspars, nondescript aluminosilicates (mainly clays), silica
      (quartz and opaline silica), and Fe(hydro)oxides. Two more site-specific groups
      (barite and ZnS) are distinguished in highly polluted fens (Bagno Bruch and Bagno
      Mikoleska) near a zinc smelter in Upper Silesia. At Bagno Bruch, peat contents of
      predominantly authigenic ZnS microspheroids range up to 1.1%. SAP originating
      from coal-burning power stations account for maximum concentrations of <21-39% of
      the inorganic fraction in the studied mires. SAP concentrations vary with depth,
      and mean spheroid diameters with distance from emission sources. A distinct
      feature of SAP is their common enrichment in Ti what questions the use of Ti as a
      proxy for soil dust in fly ash polluted bogs. As amounts of anthropogenic
      magnetic spherules, less abundant than SAP in all mires, relate to water table
      level position, they are unsuitable as tracers of air pollution. The proposed
      method is recommended for application with peats having ash contents > ~4%.

PMID- 24442579
TI  - The role of the osteopontin-integrin alphavbeta3 interaction at implantation:
      functional analysis using three different in vitro models.
AB  - STUDY QUESTION: Does the interaction between integrin and its ligand osteopontin
      (OPN) mediate embryonic attachment to endometrial epithelium at implantation?
      SUMMARY ANSWER: OPN of epithelial origin binds the receptor integrin alphavbeta3
      at the maternal surface to support adhesion during the early stages of
      implantation. WHAT IS KNOWN ALREADY: Integrin alphavbeta3 and OPN are both
      present in the endometrial luminal epithelium in the mid-secretory phase. STUDY
      DESIGN, SIZE, DURATION: Microscopy of attachment sites of blastocysts (mouse, n =
      151, human, n = 8) and OPN- or BSA-coated beads (n = 488) interacting with
      Ishikawa cell monolayers at 24 and 48 h. Levels of epithelial OPN or integrin
      alphavbeta3 were altered by siRNA-mediated targeting and the results compared
      with non-targeting siRNA or mock-transfected controls. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: In vitro modelling of early implantation with human endometrial
      cells (Ishikawa) and mouse or human embryos or ligand-coated beads.
      Immunolocalization of antigen around attached embryos was measured by image
      analysis with multiple repeats (n > 3), allowing a gradient of relative intensity
      to be detected. Attachment was quantified using a stability scale and protein
      expression documented by indirect immunofluorescence. Protein associations were
      probed by pulldown assays. MAIN RESULTS AND THE ROLE OF CHANCE: Integrin and OPN
      levels were increased in epithelial cells near to attached embryos. The pulldown
      assay confirmed OPN-integrin alphavbeta3 binding (n > 3). Decreased attachment
      stability of mouse embryos observed after siRNA knock-down of integrin
      alphavbeta3 or OPN itself, or OPN-coated beads after knock-down of integrin
      alphavbeta3, was tested for significance using Kruskal-Wallis with Dunn's post
      hoc tests. LIMITATIONS, REASONS FOR CAUTION: In vitro model. Attachment data
      using human embryos is limited by embryo availability. Mouse embryo attachment to
      human cells involves a species crossover so must be interpreted with caution.
      Ligand-coated beads allow specific molecular interactions mediating attachment to
      be probed, but obviously lack the adhesion and signaling repertoire of a live
      embryo. WIDER IMPLICATIONS OF THE FINDINGS: Some of the literature identifies
      reduced integrin alphavbeta3 expression in infertile endometrium; these findings
      predict that embryo attachment stability will be reduced in vivo if integrin
      levels are low. We suggest that the robustness of the initial attachment of the
      embryo affects its ability to progress to the post-epithelial phase of
      implantation; some poorly attached embryos will be lost. STUDY FUNDING/COMPETING
      INTEREST(S): No external funds were used for this study, which was supported by
      funds from the Universities of Manchester and Oxford. None of the authors has any
      conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

PMID- 24442580
TI  - Physical health care monitoring for people with serious mental illness.
AB  - BACKGROUND: Current guidance suggests that we should monitor the physical health
      of people with serious mental illness, and there has been a significant financial
      investment over recent years to provide this. OBJECTIVES: To assess the
      effectiveness of physical health monitoring, compared with standard care for
      people with serious mental illness. SEARCH METHODS: We searched the Cochrane
      Schizophrenia Group Trials Register (October 2009, update in October 2012), which
      is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION
      CRITERIA: All randomised clinical trials focusing on physical health monitoring
      versus standard care, or comparing i) self monitoring versus monitoring by a
      healthcare professional; ii) simple versus complex monitoring; iii) specific
      versus non-specific checks; iv) once only versus regular checks; or v) different
      guidance materials. DATA COLLECTION AND ANALYSIS: Initially, review authors (GT,
      AC, SM) independently screened the search results and identified three studies as
      possibly fulfilling the review's criteria. On examination, however, all three
      were subsequently excluded. Forty-two additional citations were identified in
      October 2012 and screened by two review authors (JX and MW), 11 of which
      underwent full screening. MAIN RESULTS: No relevant randomised trials which
      assess the effectiveness of physical health monitoring in people with serious
      mental illness have been completed. We identified one ongoing study. AUTHORS'
      CONCLUSIONS: There is still no evidence from randomised trials to support or
      refute current guidance and practice. Guidance and practice are based on expert
      consensus, clinical experience and good intentions rather than high quality
      evidence.

PMID- 24442581
TI  - 18F-FDG PET/CT is a valuable tool for relapsing polychondritis diagnose and
      therapeutic response monitoring.
AB  - OBJECTIVES: To retrospectively investigate the role of (18) F-fluorodeoxyglucose
      positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the
      diagnosis and therapeutic response in relapsing polychondritis (RP) patients.
      METHODS: (18)F-FDG PET/CT findings were reviewed in six RP patients. The initial
      scans were performed for all patients, follow-up scans were performed during
      steroid therapy for five patients. Changes in the abnormal lesions and the
      maximal standard uptake value (SUVmax) were analyzed. RESULTS: The initial PET/CT
      scans revealed intense FDG uptake in the cartilages for all six patients. The
      lesions of abnormal FDG uptake were tracheal/bronchial cartilage (n = 4),
      costicartilage (n = 4), nasal cartilage (n = 3), cricoid cartilage (n = 3),
      auricular cartilage (n = 3), arytenoid cartilage (n = 3), thyroid cartilage (n =
      2), hyoid cartilage (n = 1) and mediastinum lymph node (n = 1). The mean visual
      score and the mean SUVmax were 2.96 +/- 0.20 and 4.10 +/- 0.6. The intense uptake
      reduced or disappeared during steroid therapy for five patients, the mean visual
      score and the mean SUVmax were 1.58 +/- 1.4 and 1.51 +/- 1.4. CONCLUSIONS: (18)F
      FDG PET/CT enables the acquisition of both morphologic and glucose metabolic of
      the related cartilage structures. It plays a valuable role in assessing almost
      all cartilage and detecting RP, which is a better selection of a biopsy site as
      well as therapeutic response monitoring.

PMID- 24442578
TI  - TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72
      hexanucleotide repeat expansions.
AB  - Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72)
      have recently been linked to frontotemporal lobar degeneration (FTLD) and
      amyotrophic lateral sclerosis, and may be the most common genetic cause of both
      neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the
      most common neuropathological subtype of FTLD, characterized by inclusions of TAR
      DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that
      TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations,
      with the major (risk) allele of rs1990622 associating with earlier age at onset
      of disease. Here, we report that rs1990622 genotype affects age at death in a
      single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14),
      with the major allele correlated with later age at death (p = 0.024). We
      replicate this modifier effect in a 30-site international neuropathological
      cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that
      the major allele associates with later age at death (p = 0.016), as well as later
      age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at
      onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72
      expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions.
      Intriguingly, the genotype that confers increased risk for developing FTLD-TDP
      (major, or T, allele of rs1990622) is associated with later age at onset and
      death in C9orf72 expansion carriers, providing an example of sign epistasis in
      human neurodegenerative disease.

PMID- 24442583
TI  - Characteristics of medical students and residents who select psychiatry :
      implications for recruitment.
AB  - Effective recruitment of psychiatric residents begins with understanding medical
      students' motivations for entering psychiatry. The author reviews the recent
      literature on the personalities of medical students interested in psychiatry
      compared with those interested in other specialties, the positive and negative
      factors that medical students cite when deciding whether to enter psychiatry, and
      the variables that are important to medical students and residents when selecting
      psychiatry residency programs. The implications of these studies for enhancing
      recruitment into psychiatry are discussed. 

PMID- 24442582
TI  - SAPTA: a new design tool for improving TALE nuclease activity.
AB  - Transcription activator-like effector nucleases (TALENs) have become a powerful
      tool for genome editing due to the simple code linking the amino acid sequences
      of their DNA-binding domains to TALEN nucleotide targets. While the initial TALEN
      design guidelines are very useful, user-friendly tools defining optimal TALEN
      designs for robust genome editing need to be developed. Here we evaluated
      existing guidelines and developed new design guidelines for TALENs based on 205
      TALENs tested, and established the scoring algorithm for predicting TALEN
      activity (SAPTA) as a new online design tool. For any input gene of interest,
      SAPTA gives a ranked list of potential TALEN target sites, facilitating the
      selection of optimal TALEN pairs based on predicted activity. SAPTA-based TALEN
      designs increased the average intracellular TALEN monomer activity by >3-fold,
      and resulted in an average endogenous gene-modification frequency of 39% for
      TALENs containing the repeat variable di-residue NK that favors specificity
      rather than activity. It is expected that SAPTA will become a useful and flexible
      tool for designing highly active TALENs for genome-editing applications. SAPTA
      can be accessed via the website at
      http://baolab.bme.gatech.edu/Research/BioinformaticTools/TAL_targeter.html. 

PMID- 24442585
TI  - Erratum to: Residency Education, Work-Related Issues, and Organizational and
      Occupational Psychiatry.

PMID- 24442584
TI  - Introducing community-based care of the chronically ill into residency education.
AB  - Few departments have the resources to support an ideal program in community
      psychia-try. In this article, the authors discuss the difficulties and benefits
      of introducing long-term community-based treatment of the chronically mentally
      ill into a residency program with limited resources of time and personnel The
      residents initially were fearful of the program and tended to avoid its unique
      community aspects. The authors describe haw they dealt with these problems and
      haw the program evolved into a well-accepted part of the residency aver its first
      4 years of operation. The authors conclude that, even on a time budget of 4 to 6
      hours weekly, residents can have a meaningful learning experience in community
      based care of the chronically mentally ill. 

PMID- 24442586
TI  - Posttraumatic stress disorder symptoms in resident physicians related to their
      internship.
AB  - To evaluate whether stresses experienced by physicians during internship are
      associated with posttraumatic stress disorder (PTSD) symptoms, the authors
      administered a standardized questionnaire to assess PTSD symptoms, depressive and
      anxiety symptoms, and social supports to 212 residents. Thirteen percent of
      residents met diagnostic criteria for PTSD, including 20% of the women and 9% of
      the men. PTSD symptoms were significantly more frequent in residents who were
      single or divorced at the time the questionnaire was administered. There were
      significant positive correlations between PTSD symptoms and symptoms of both
      current anxiety and depression, and a significant negative correlation existed
      between social support and PTSD symptoms. PTSD symptoms attributed to stresses
      associated with internship, which may be deleterious to physician well-being and
      potentially to patient care, and suggest the importance of making major changes
      in postgraduate medical training. 

PMID- 24442587
TI  - Perceived personal and institutional influences on child and adolescent
      psychiatry research careers.
AB  - To assess possible influences on the professional success of child and adolescent
      psychiatry investigators, all 187 physician-first authors of research posters
      presented at 4 annual meetings of the American Academy of Child and Adolescent
      Psychiatry were asked to complete a questionnaire. Responses numbered 147 (79%),
      with 80% (117/147) spontaneously naming one or more workplace factors, such as
      excessive clinical, administrative, or teaching demands, as hindrances to their
      success as researchers. The most important hindrances andfacilitatingfactors are
      discussed and suggestions are made to promote the development of research
      investigators in child and adolescent psychiatry. 

PMID- 24442588
TI  - Sabbaticals : A User's Guide.
AB  - Academic sabbatical leaves have been offered in the United States since 1880. The
      author discusses the historical background and rationale for sabbaticals, their
      evaluation, and practical tips for those planning such an academic leave. 

PMID- 24442589
TI  - Teaching interpersonal psychotherapy to psychiatric residents.
AB  - Time-limited therapies are increasingly important components of clinical
      practice. The author describes his experience in teaching interpersonal
      psychotherapy and brief psychotherapy generally to PGY-3 psychiatric residents in
      two residency programs. Although residents lack psychotherapeutic experience,
      they appear to compensate f or needed security in the therapeutic role with
      enthusiasm and vigor, and to adjust relatively easily to the demands of
      conducting an active, time-limited approach. Videotaping sessions and having
      appropriately trained supervisors are important factors for program success. 

PMID- 24442591
TI  - Helping our students feel how mental illness impacts lives.

PMID- 24442592
TI  - The Cultural Relevance of Mindfulness Meditation as a Health Intervention for
      African Americans: Implications for Reducing Stress-Related Health Disparities.
AB  - African Americans experience a disproportionate rate of stress-related health
      conditions compared to European Americans. Mindfulness meditation has been shown
      to be effective for managing stress and various stress-related health conditions.
      This study explored the cultural relevance of mindfulness meditation training for
      African Americans adults. Fifteen African American adults with past or current
      experience with mindfulness meditation training were interviewed. Participants
      felt that mindfulness meditation helped them with enhanced stress management,
      direct health improvement, and enhanced self-awareness and purposefulness. They
      felt that they would recommend it and that other African Americans would be open
      to the practice but suggested that its presentation may need to be adapted. They
      suggested emphasizing the health benefits, connecting it to familiar spiritual
      ideology and cultural practices, supplementing the reading material with African
      American writers, increasing communication (education, instructor availability,
      "buddy system," etc.), and including African Americans as instructors and
      participants. By implementing minor adaptations that enhance cultural relevance,
      mindfulness meditation can be a beneficial therapeutic intervention for this
      population. 

PMID- 24442593
TI  - Alternatives to polysomnography (PSG): a validation of wrist actigraphy and a
      partial-PSG system.
AB  - The objective of this study was to assess the validity of a sleep/wake activity
      monitor, an energy expenditure activity monitor, and a partial-polysomnography
      system at measuring sleep and wake under identical conditions. Secondary aims
      were to evaluate the sleep/wake thresholds for each activity monitor and to
      compare the three devices. To achieve these aims, two nights of sleep were
      recorded simultaneously with polysomnography (PSG), two activity monitors, and a
      partial-PSG system in a sleep laboratory. Agreement with PSG was evaluated epoch
      by epoch and with summary measures including total sleep time (TST) and wake
      after sleep onset (WASO). All of the devices had high agreement rates for
      identifying sleep and wake, but the partial-PSG system was the best, with an
      agreement of 91.6% +/- 5.1%. At their best thresholds, the sleep/wake monitor
      (medium threshold, 87.7% +/- 7.6%) and the energy expenditure monitor (very low
      threshold, 86.8% +/- 8.6%) had similarly high rates of agreement. The summary
      measures were similar to those determined by PSG, but the partial-PSG system
      provided the most consistent estimates. Although the partial-PSG system was the
      most accurate device, both activity monitors were also valid for sleep
      estimation, provided that appropriate thresholds were selected. Each device has
      advantages, so the primary consideration for researchers will be to determine
      which best suits a given research design.

PMID- 24442594
TI  - Purification and characterization of alkaline chitinase from Paenibacillus
      pasadenensis NCIM 5434.
AB  - An alkaline chitinase was purified from the bacterium Paenibacillus pasadenensis
      NCIM 5434 isolated from alkaline littoral soil of Lonar Lake. The chitinase was
      purified by ammonium sulfate precipitation followed by DEAE cellulose column
      chromatography. Enzyme was purified by 8.87 folds with 24.96% yield. Molecular
      characterization through SDS-PAGE analysis showed that it has molecular weight of
      about ~35 kDa. The enzyme kinetics studies of purified chitinase revealed the
      following characteristics, Km 6.25 mg ml(-1) and Vmax 434.78 uM for colloidal
      chitin as a substrate. The chitinase showed optimum pH 10 and temperature 37 
      degrees C. The enzyme exhibited significant activity up to 3% salt concentration,
      indicating saline nature. Its activity was enhanced with calcium, potassium and
      magnesium; whereas copper and mercury were found to be inhibitory. Since, it
      showed antifungal activity against Penicillium and Aspergillus, it could be used
      as powerful biocontrol agent.

PMID- 24442595
TI  - Looking for age-related growth decline in natural forests: unexpected biomass
      patterns from tree rings and simulated mortality.
AB  - Forest biomass growth is almost universally assumed to peak early in stand
      development, near canopy closure, after which it will plateau or decline. The
      chronosequence and plot remeasurement approaches used to establish the decline
      pattern suffer from limitations and coarse temporal detail. We combined annual
      tree ring measurements and mortality models to address two questions: first, how
      do assumptions about tree growth and mortality influence reconstructions of
      biomass growth? Second, under what circumstances does biomass production follow
      the model that peaks early, then declines? We integrated three stochastic
      mortality models with a census tree-ring data set from eight temperate forest
      types to reconstruct stand-level biomass increments (in Minnesota, USA). We
      compared growth patterns among mortality models, forest types and stands. Timing
      of peak biomass growth varied significantly among mortality models, peaking 20-30
      years earlier when mortality was random with respect to tree growth and size,
      than when mortality favored slow-growing individuals. Random or u-shaped
      mortality (highest in small or large trees) produced peak growth 25-30% higher
      than the surviving tree sample alone. Growth trends for even-aged, monospecific
      Pinus banksiana or Acer saccharum forests were similar to the early peak and
      decline expectation. However, we observed continually increasing biomass growth
      in older, low-productivity forests of Quercus rubra, Fraxinus nigra, and Thuja
      occidentalis. Tree-ring reconstructions estimated annual changes in live biomass
      growth and identified more diverse development patterns than previous methods.
      These detailed, long-term patterns of biomass development are crucial for
      detecting recent growth responses to global change and modeling future forest
      dynamics.

PMID- 24442597
TI  - Suboptimal use of imaging in the new (National Comprehensive Cancer Network)
      International Prognostic Index for diffuse large B-cell lymphoma.

PMID- 24442596
TI  - Arterial and fat tissue inflammation are highly correlated: a prospective 18F-FDG
      PET/CT study.
AB  - PURPOSE: There is evidence that the link between obesity and cardiovascular
      disease might relate to inflammation in both fat tissue and the arterial wall.
      (18)F-FDG uptake on PET is a surrogate marker of vessel wall inflammation. The
      aim of the study was to measure FDG uptake in both regions using PET and identify
      links between adipose and arterial inflammation. METHODS: Included in the study
      were 173 cardiovascular patients who were prospectively imaged with FDG PET/CT.
      Arterial FDG uptake was measured in the carotid arteries and ascending aorta. The
      same was done in fat tissue in the neck, the presternal region (both
      subcutaneous) and the pericardium. FDG uptake was quantified as average maximal
      target-to-background ratio (mean TBR max). Multivariate regression analyses were
      performed to identify significant associations between arterial and adipose
      tissue FDG uptake and clinical variables as given by the standardized correlation
      coefficient (beta). RESULTS: FDG uptake values in all fat tissue regions were
      highly predictive of vascular FDG uptake in both the carotids (beta 0.262, p <
      0.0001, in the neck subcutaneous region) and aorta (beta 0.22, p = 0.008, in the
      chest pericardial region; beta 0.193, p = 0.019, in the chest subcutaneous
      region). Obesity was significantly associated with elevated FDG uptake in adipose
      tissue (beta 0.470, p < 0.0001, in the neck subcutaneous region; beta 0.619, p =
      0.028, in the chest subcutaneous region; beta 0.978, p = 0.035, in the chest
      pericardial region). CONCLUSION: FDG uptake in diverse fat tissue regions was
      significantly associated with arterial FDG uptake, a reasonable surrogate of
      inflammation. Increasing body weight significantly predicted the level of fatty
      inflammation. FDG PET therefore provides imaging evidence of an inflammatory link
      between fat tissue and the vasculature in patients with cardiovascular disease.

PMID- 24442598
TI  - Impact of initial PET/CT staging in terms of clinical stage, management plan, and
      prognosis in 592 patients with non-small-cell lung cancer.
AB  - PURPOSE: Our objective was to determine the impact of initial (18)F-FDG PET/CT
      (PET/CT) staging on clinical stage and the management plan and the prognostic
      value of PET/CT in patients with non-small-cell lung cancer (NSCLC). METHODS: We
      retrospectively reviewed the records of 592 patients with NSCLC who were referred
      to The University of Texas MD Anderson Cancer Center during 2002/2011 and had
      both PET/CT and conventional CT for initial staging. Clinical stages and
      management plans were compared between PET/CT and CT. The impact of PET/CT on
      management plans was considered medium/high when PET/CT changed the planned
      treatment modality or treatment intent. PET/CT and CT stages were compared with
      all-cause mortality and survival rates. We also assessed potential prognostic
      factors for progression-free survival (PFS) and overall survival (OS). RESULTS:
      PET/CT changed the stage in 170 patients (28.7 %; 16.4 % upstaged, 12.3 %
      downstaged). PET/CT had a medium/high impact on the management plan in 220
      patients (37.2 %). PFS and OS were significantly worse in patients with upstaged
      disease than in patients with no change in stage (median PFS 29.0 vs. 53.8
      months, P < 0.001; median OS:64.7 vs. 115.9 months, P = 0.006). PFS and OS were
      significantly worse in patients with medium/high impact of PET/CT than in
      patients with no/low impact of PET/CT (median PFS 24.7 vs. 60.6 months, P <
      0.001; median OS 64.7 vs. 115.9 months, P < 0.001). In multivariate analysis, a
      medium/high impact of PET/CT was an independent predictor of worse PFS (hazard
      ratio, HR, 1.73; 95 % CI 1.30 - 2.29; P = 0.0002) and OS (HR 1.84; 95 % CI 1.26 -
      2.69; P = 0.002). CONCLUSION: Initial PET/CT staging not only impacts stage and
      management plan but also has prognostic value.

PMID- 24442599
TI  - FDG gated cardiac PET at rest and immediately after dobutamine stress.

PMID- 24442600
TI  - The role of SPECT/CT in radioembolization of liver tumours.
AB  - Radioembolization (RE) with (90)Y microspheres is a promising catheter-based
      therapeutic option for patients with unresectable primary and metastatic liver
      tumours. Its rationale arises from the dual blood supply of liver tissue through
      the hepatic artery and the portal vein. Metastatic hepatic tumours measuring >3
      mm derive 80 - 100 % of their blood supply from the arterial rather than the
      portal hepatic circulation. Typically, an angiographic evaluation combined with
      (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) scan precedes therapy to map the
      tumour feeding vessels as well as to avoid the inadvertent deposition of
      microspheres in organs other than the liver. Prior to administration of (99m)Tc
      MAA, prophylactic coil embolization of the gastroduodenal artery is recommended
      to avoid extrahepatic deposition of the microspheres. SPECT/CT allows direct
      correlation of anatomic and functional information in patients with unresectable
      liver disease. SPECT/CT is recommended to assess intrahepatic distribution as
      well as extrahepatic gastrointestinal uptake in these patients. Pretherapeutic
      SPECT/CT is an important component of treatment planning including catheter
      positioning and dose finding. A post-therapy bremsstrahlung (BS) scan should
      follow RE to verify the distribution of the administered tracer. BS SPECT/CT
      imaging enables better localization and definition of intrahepatic and possible
      extrahepatic sphere distribution and to a certain degree allows posttreatment
      dosimetry. In this paper we address the usefulness and significance of SPECT/CT
      in therapy planning and therapy monitoring of RE.

PMID- 24442601
TI  - Intraoperative fabrication of patient-specific moulded implants for skull
      reconstruction: single-centre experience of 28 cases.
AB  - BACKGROUND: Intraoperatively fabricated polymethylmethacrylate (PMMA) implants
      based on computer-designed moulds were used to improve cosmetic results after
      hard tissue replacement. To assess the implant's cosmetic and functional results
      we performed both subjective and objective assessments. METHODS: This
      retrospective analysis was performed using a cohort of 28 patients who received
      PMMA implants between February 2009 and March 2012. The cosmetic and functional
      results were assessed using a patient questionnaire. Furthermore an objective
      volumetric subtraction score (0-100) was applied and implant thickness, as well
      as gaps and tiers, were measured. RESULTS: Patients mainly judged their cosmetic
      result as "good". Two of the 28 patients found their cosmetic result
      unfavourable. The functional result and stability was mainly judged to be good.
      Measurements of implant thickness showed a very high correlation with the
      thickness of the contralateral bone. Volumetric subtraction led to a median
      quality of 80 on a scale from 0 to 100. Median gaps around the margins of the
      implant were 1.5 mm parietally, 1.7 mm frontally and 3.5 mm fronto-orbitally, and
      median tiers were 1.2 mm, 0 mm and 0 mm respectively. The overall rate of
      surgical revisions was 10.7 % (three patients). Two patients suffered from wound
      healing disturbances (7.1 %). The overall complication rate was comparable to
      other reports in the literature. CONCLUSIONS: Implantation of intraoperatively
      fabricated patient-specific moulded implants is a cost-effective and safe
      technique leading to good clinical results with a low complication rate.

PMID- 24442602
TI  - Contributions of the insula to cognition and emotion.
AB  - Historically, the insula was considered primary gustatory cortex. Now it is known
      to play a more comprehensive role in the processing of sensory information,
      including acting as primary cortex for interoceptive information, including
      autonomic nervous system mediated changes. As such, it is critical for emotional
      feeling in accord with the James-Lange theory, a role previously ascribed to the
      limbic system. Neuroimaged abnormal grey matter volumes or activity levels in the
      insula have been associated with schizophrenia, eating disorders, anxiety and
      mood disorders, conduct disorder, autism, addiction, and chronic pain. The
      significance of these abnormal activity patterns remains theoretical.
      Neuropsychological studies have linked dominant insula injury with various
      symptoms of aphasia, but its exact role in language processing remains uncertain
      as most cases involve lesions that extend into perisylvian language zones.
      Functional neuroimaging studies have found insula hyper-activations, typically in
      conjunction with anterior cingulate cortex, for all manner of experimental tasks
      including those involving perception, intentional action, and consciousness. Such
      neuroimaged activity is unlikely to be task-specific, but rather reflective of
      generic changes in autonomic activity in response to salience, homeostatic
      incongruence, or cognitive challenge. 

PMID- 24442603
TI  - A suspicion index for early diagnosis and treatment of cerebrotendinous
      xanthomatosis.
AB  - BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid
      storage disorder characterized by a heterogeneous presentation and a broad
      spectrum of clinical manifestations. Since early diagnosis and replacement
      therapy with chenodeoxycholic acid can prevent clinical deterioration, our aim
      was to develop a diagnostic tool to identify and treat CTX patients at an initial
      stage of the disease. METHODS: We devised a suspicion index, composed of weighted
      scores assigned to indicators such as family history characteristics and common
      systemic and neurological features, on the basis of a pooled analysis of selected
      international CTX series. The indicators were classified as very strong (score
      100), strong (50) or moderate (25). The suspicion index was then applied
      retrospectively to our CTX population. RESULTS: Early systemic signs such as
      cataract, diarrhea and neonatal cholestatic jaundice were considered strong
      indicators, together with neurological features such as intellectual impairment,
      psychiatric disturbances, ataxia, spastic paraparesis and dentate nuclei
      abnormalities at MRI. Tendon xanthomas were regarded as very strong indicators,
      as was an affected sibling. A total score >= 100 warranted serum cholestanol
      assessment. Elevated cholestanol or a total score >= 200, with one very strong or
      four strong indicators, warranted CYP27A1 gene analysis. In our patients, age at
      diagnosis was 35.5 +/- 11.8 years (mean +/- standard deviation), whereas with the
      diagnostic tool it became 10.6 +/- 9.8 years (p < 0.01). CONCLUSIONS: Our
      suspicion index provides a simple and inexpensive diagnostic tool allowing
      diagnosis and treatment of CTX before neurological disability occurs.

PMID- 24442604
TI  - N-Acetylcysteine counteracts oxidative stress and protects alveolar epithelial
      cells from lung contusion-induced apoptosis in rats with blunt chest trauma.
AB  - The aim of this study was to investigate the protective effects of N
      acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs
      of rats following blunt chest trauma. The rats were randomly divided into three
      groups: control, contusion, and contusion + NAC. All the rats, apart from those
      in the control group, performed moderate lung contusion. A daily intramuscular
      NAC injection (150 mg/kg) was given immediately following the blunt chest trauma
      and was continued for two additional days following cessation of the trauma.
      Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde
      (MDA) level, histopathology, and epithelial cell apoptosis using terminal
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active
      caspase-3 immunostaining. In addition, we immunohistochemically evaluated the
      expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest
      trauma-induced lung contusion resulted in severe histopathological injury, as
      well as an increase in the MDA level and in the number of cells identified on
      TUNEL assay together with active caspase-3 positive epithelial cells, but a
      decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC
      treatment effectively attenuated histopathologic, peroxidative, and apoptotic
      changes, as well as reducing alterations in SP-D expression in the lung tissue.
      These findings indicate that the beneficial effects of NAC administrated
      following blunt chest trauma is related to the regulation of oxidative stress and
      apoptosis. 

PMID- 24442605
TI  - Acute post-partum urinary retention: analysis of risk factors, a case-control
      study.
AB  - PURPOSE: The aim of this retrospective case-control study was to assess clinical
      factors that can predict the occurrence of post-partum urinary retention (PPUR)
      and evaluate their influence as independent risk factors. METHODS: Between
      January 2008 and December 2010, 11,108 vaginal deliveries were performed. 105
      women who suffered from PPUR were detected by retrospective data analysis. PPUR
      was defined as the inability to have spontaneous micturition within 6 h after
      vaginal delivery. RESULTS: Data analysis detected six risk factors for PPUR on
      set: primiparity, vacuum-assisted delivery, uterine fundal pressure during the
      second stage of labor (Kristeller's maneuver), a longer second stage of labor,
      medio-lateral episiotomy, initial higher dose of epidural analgesia.
      Nevertheless, logistic regression showed that only vacuum-assisted delivery and
      Kristeller's maneuver were significant independent risk factors (P = 0.001 and
      0.009, respectively). CONCLUSIONS: Our study identified these risk factors as the
      cause of mechanical and neurological damage, which can lead to post-partum
      urinary retention. By early diagnosis, a prompt and appropriate management of
      PPUR can be established in order to assure a rapid return to normal bladder
      function after vaginal delivery.

PMID- 24442606
TI  - Progressive multifocal leukoencephalopathy after natalizumab discontinuation: few
      and true?

PMID- 24442607
TI  - External validation of the Heidenreich criteria for patient selection for
      unilateral or bilateral retroperitoneal lymph node dissection for post
      chemotherapy residual masses of testicular cancer.
AB  - OBJECTIVE: To validate the Heidenreich criteria for patient selection for
      unilateral retroperitoneal lymph node dissection (RPLND) for residual masses
      after chemotherapy for nonseminomatous germ cell tumor (NSGCT). SUBJECTS/PATIENTS
      AND METHODS: For validation, the data of 59 patients who underwent RPLND for
      residual masses of NSGCT were used. Of these patients, 23 (39 %) qualified for a
      modified RPLND, the others had an indication for a bilateral dissection. Results
      from histopathology after RPLND and follow-up data for relapse inside or outside
      the zone of the resection template were considered for validation. RESULTS: In
      the study cohort, median age at time of RPLND was 31 years. The 2-year disease
      free survival was 90 and 96 % for the bilateral and the unilateral RPLND
      patients, respectively. Overall, 8 (14 %) relapses were observed after a median
      follow-up of 54 month. Of these, 6 were outside of the resection field and 2 were
      in-field. Of the 23 patients with indication for a modified RPLND, 1 patient
      relapsed in the contralateral testis and 1 inside the modified RPLND template. No
      relapse was observed outside the modified RPLND field and inside the untouched
      contralateral RPLND field. The Heidenreich criteria did therefore not misclassify
      a single patient. CONCLUSION: The Heidenreich criteria for the selection of
      candidates for unilateral RPLND for residual masses after chemotherapy allow a
      highly reliable selection of patients. The application of the Heidenreich
      criteria can help to reduce comorbidity and invasiveness of RPLND.

PMID- 24442608
TI  - Increasing use of third-generation cephalosporins for pneumonia in the emergency
      department: may some prescriptions be avoided?
AB  - Third-generation cephalosporins are used to treat inpatients with community
      acquired pneumonia. Some of these prescriptions may be avoided, i.e. replaced by
      agents less likely to promote ESBL-mediated resistance. Our objectives were to
      assess the recent trend of third-generation cephalosporins use for pneumonia in
      the emergency department, and the proportion of avoidable prescriptions. This was
      a retrospective study of patients treated for community-acquired pneumonia in an
      emergency department, and subsequently hospitalized in non ICU wards. Third
      generation cephalosporin prescriptions were presumed unavoidable if they met both
      criteria: (i) age >= 65 yr or comorbid condition, and (ii) allergy or intolerance
      to penicillin, or failure of penicillin first-line therapy, or treatment with
      penicillin in three previous months. Prescriptions were otherwise deemed
      avoidable. The proportion of patients treated with a third generation
      cephalosporin increased significantly from 13.9 % (6.9-24.1 %) in 2002 to 29.5 %
      (18.5-42.6 %) in 2012 (OR = 1.07 [1.01-1.14] , P = 0.02). This increase was
      independent from other factors associated with the prescription of a third
      generation cephalosporin (immunocompromising condition, antibacterial therapy in
      three previous months, fluid resuscitation and REA-ICU class). Treatment with
      third-generation cephalosporin was avoidable in 118 out of 147 patients (80.3 %
      [72.7-86.2 %]). On day 7 after admission in the ED, treatment with third
      generation cephalosporins was stopped or de-escalated in, respectively, 17 % and
      32 % of patients. Antibiotic stewardship programs should be implemented to
      restrict the third-generation cephalosporins use for pneumonia in the emergency
      department.

PMID- 24442609
TI  - The N-terminal extension of S12 influences small ribosomal subunit assembly in
      Escherichia coli.
AB  - The small subunit (SSU) of the ribosome of E. coli consists of a core of
      ribosomal RNA (rRNA) surrounded peripherally by ribosomal proteins (r-proteins).
      Ten of the 15 universally conserved SSU r-proteins possess nonglobular regions
      called extensions. The N-terminal noncanonically structured extension of S12
      traverses from the solvent to intersubunit surface of the SSU and is followed by
      a more C-terminal globular region that is adjacent to the decoding center of the
      SSU. The role of the globular region in maintaining translational fidelity is
      well characterized, but a role for the S12 extension in SSU structure and
      function is unknown. We examined the effect of stepwise truncation of the
      extension of S12 in SSU assembly and function in vitro and in vivo. Examination
      of in vitro assembly in the presence of sequential N-terminal truncated variants
      of S12 reveals that N-terminal deletions of greater than nine amino acids exhibit
      decreased tRNA-binding activity and altered 16S rRNA architecture particularly in
      the platform of the SSU. While wild-type S12 expressed from a plasmid can rescue
      a genomic deletion of the essential gene for S12, rpsl; N-terminal deletions of
      S12 exhibit deleterious phenotypic consequences. Partial N-terminal deletions of
      S12 are slow growing and cold sensitive. Strains bearing these truncations as the
      sole copy of S12 have increased levels of free SSUs and immature 16S rRNA as
      compared with the wild-type S12. These differences are hallmarks of SSU
      biogenesis defects, indicating that the extension of S12 plays an important role
      in SSU assembly. 

PMID- 24442610
TI  - tRNA anticodon shifts in eukaryotic genomes.
AB  - Embedded in the sequence of each transfer RNA are elements that promote specific
      interactions with its cognate aminoacyl tRNA-synthetase. Although many such
      "identity elements" are known, their detection is difficult since they rely on
      unique structural signatures and the combinatorial action of multiple elements
      spread throughout the tRNA molecule. Since the anticodon is often a major
      identity determinant itself, it is possible to switch between certain tRNA
      functional types by means of anticodon substitutions. This has been shown to have
      occurred during the evolution of some genomes; however, the scale and relevance
      of "anticodon shifts" to the evolution of the tRNA multigene family is unclear.
      Using a synteny-conservation-based method, we detected tRNA anticodon shifts in
      groups of closely related species: five primates, 12 Drosophila, six nematodes,
      11 Saccharomycetes, and 61 Enterobacteriaceae. We found a total of 75 anticodon
      shifts: 31 involving switches of identity (alloacceptor shifts) and 44 between
      isoacceptors that code for the same amino acid (isoacceptor shifts). The relative
      numbers of shifts in each taxa suggest that tRNA gene redundancy is likely the
      driving factor, with greater constraint on changes of identity. Sites that
      frequently covary with alloacceptor shifts are located at the extreme ends of the
      molecule, in common with most known identity determinants. Isoacceptor shifts are
      associated with changes in the midsections of the tRNA sequence. However, the
      mutation patterns of anticodon shifts involving the same identities are often
      dissimilar, suggesting that alternate sets of mutation may achieve the same
      functional compensation. 

PMID- 24442611
TI  - Endogenous U2.U5.U6 snRNA complexes in S. pombe are intron lariat spliceosomes.
AB  - Excision of introns from pre-mRNAs is mediated by the spliceosome, a multi
      megadalton complex consisting of U1, U2, U4/U6, and U5 snRNPs plus scores of
      associated proteins. Spliceosome assembly and disassembly are highly dynamic
      processes involving multiple stable intermediates. In this study, we utilized a
      split TAP-tag approach for large-scale purification of an abundant endogenous
      U2.U5.U6 complex from Schizosaccharomyces pombe. RNAseq revealed this complex to
      largely contain excised introns, indicating that it is primarily ILS (intron
      lariat spliceosome) complexes. These endogenous ILS complexes are remarkably
      resistant to both high-salt and nuclease digestion. Mass spectrometry analysis
      identified 68, 45, and 43 proteins in low-salt-, high-salt-, and micrococcal
      nuclease-treated preps, respectively. The protein content of a S. pombe ILS
      complex strongly resembles that previously reported for human spliced product (P)
      and Saccharomyces cerevisiae ILS complexes assembled on single pre-mRNAs in
      vitro. However, the ATP-dependent RNA helicase Brr2 was either substoichiometric
      in low-salt preps or completely absent from high-salt and MNase preps. Because
      Brr2 facilitates spliceosome disassembly, its relative absence may explain why
      the ILS complex accumulates logarithmically growing cultures and the inability of
      S. pombe extracts to support in vitro splicing.

PMID- 24442612
TI  - Molecular crowders and cosolutes promote folding cooperativity of RNA under
      physiological ionic conditions.
AB  - Folding mechanisms of functional RNAs under idealized in vitro conditions of
      dilute solution and high ionic strength have been well studied. Comparatively
      little is known, however, about mechanisms for folding of RNA in vivo where
      Mg(2+) ion concentrations are low, K(+) concentrations are modest, and
      concentrations of macromolecular crowders and low-molecular-weight cosolutes are
      high. Herein, we apply a combination of biophysical and structure mapping
      techniques to tRNA to elucidate thermodynamic and functional principles that
      govern RNA folding under in vivo-like conditions. We show by thermal denaturation
      and SHAPE studies that tRNA folding cooperativity increases in physiologically
      low concentrations of Mg(2+) (0.5-2 mM) and K(+) (140 mM) if the solution is
      supplemented with physiological amounts (~ 20%) of a water-soluble neutral
      macromolecular crowding agent such as PEG or dextran. Low-molecular-weight
      cosolutes show varying effects on tRNA folding cooperativity, increasing or
      decreasing it based on the identity of the cosolute. For those additives that
      increase folding cooperativity, the gain is manifested in sharpened two-state
      like folding transitions for full-length tRNA over its secondary structural
      elements. Temperature-dependent SHAPE experiments in the absence and presence of
      crowders and cosolutes reveal extent of cooperative folding of tRNA on a
      nucleotide basis and are consistent with the melting studies. Mechanistically,
      crowding agents appear to promote cooperativity by stabilizing tertiary
      structure, while those low molecular cosolutes that promote cooperativity
      stabilize tertiary structure and/or destabilize secondary structure. Cooperative
      folding of functional RNA under physiological-like conditions parallels the
      behavior of many proteins and has implications for cellular RNA folding kinetics
      and evolution.

PMID- 24442614
TI  - The entry of ions and molecules into roots: an investigation using electron
      opaque tracers.
AB  - Various solutions containing ions or molecules which may be visualized in the
      electron microscope have been presented to barley (Hordeum vulgare L.) roots.
      Large molecules such as gold sol particles (<6.0 nm) or ferritin (approx. 12.0
      nm) were not found to be taken into the cytoplasm of any cells. Very dilute
      solutions of uranyl acetate or lanthanum nitrate resulted in the presence of
      typical electron-opaque crystals in the cortical apoplasm, as well as in
      cytoplasmic vesicles of cortical and some endodermal cells, but not in the
      cytoplasm or cell walls of stellar cells. Colloidal lanthanum hydroxide, however,
      while also impeded by the Casparian band, accumulated in vesicles in endodermal
      cells, and also penetrated into the stele.These results support the concept that
      different pathways exist for the movement of water and different ions across
      barley roots. They also indicate the relevance of the Casparian bands, the
      suberin lamellae, the formation of endocytotic vesicles, and the plasmodesmata,
      in studies on water and ion uptake. 

PMID- 24442615
TI  - Effect of phytochrome on development of catalase activity and isoenzyme pattern
      in mustard (Sinapis alba L.) seedlings : A reinvestigation.
AB  - In contrast to an earlier publication (Drumm et al., Cytobiol. 2, 335, 1970), a
      definite enhancement by phytochrome of the catalase level in mustard (Sinapis
      alba L.) cotyledons can be demonstrated. This response can be obtained either
      with continuous far-red light or with short red pulses, the effect of which is
      reversible by short far-red pulses. From the comparison of the time courses of
      catalase activity with the time courses of glyoxysomal (isocitrate lyase) and
      peroxisomal (glycolate oxidase, glyoxylate reductase) marker enzymes in dark
      grown and far-red irradiated cotyledons, there appears to be a close relationship
      between the catalase present in darkness and glyoxysomes and between the
      phytochrome-stimulated portion of total catalase and peroxisomes,
      respectively.The isoenzyme pattern of catalase shows 3 strong and several weaker
      bands in dark grown cotyledons. Irradiation with white or far-red light leads to
      a more complex pattern with at least 12 detectable bands. The isoenzymes
      increased by light supplement rather than replace the isoenzymes present in
      darkness. This is true also in cotyledons and true leaves of white light grown
      plants which do not possess glyoxysomes. In the hypocotyl of the seedling,
      catalase formation is depressed by far-red light and no change in the isoenzyme
      pattern is observed.It is concluded that the development of peroxisomes in the
      cotyledons is specifically controlled by phytochrome and that this subcellular
      differentiation also involves the control of catalase, a marker enzyme for both
      glyoxysomes and peroxisomes. The implications of these results with respect to
      the developmental origin of peroxisomes in cotyledons of fat-storing, potentially
      photosynthetically active cotyledons is discussed. 

PMID- 24442613
TI  - The DExD/H-box ATPase Prp2p destabilizes and proofreads the catalytic RNA core of
      the spliceosome.
AB  - After undergoing massive RNA and protein rearrangements during assembly, the
      spliceosome undergoes a final, more subtle, ATP-dependent rearrangement that is
      essential for catalysis. This rearrangement requires the DEAH-box protein Prp2p,
      an RNA-dependent ATPase. Prp2p has been implicated in destabilizing interactions
      between the spliceosome and the protein complexes SF3 and RES, but a role for
      Prp2p in destabilizing RNA-RNA interactions has not been explored. Using directed
      molecular genetics in budding yeast, we have found that a cold-sensitive prp2
      mutation is suppressed not only by mutations in SF3 and RES components but also
      by a range of mutations that disrupt the spliceosomal catalytic core element
      U2/U6 helix I, which is implicated in juxtaposing the 5' splice site and branch
      site and in positioning metal ions for catalysis within the context of a putative
      catalytic triplex; indeed, mutations in this putative catalytic triplex also
      suppressed a prp2 mutation. Remarkably, we also found that prp2 mutations rescue
      lethal mutations in U2/U6 helix I. These data provide evidence that RNA elements
      that comprise the catalytic core are already formed at the Prp2p stage and that
      Prp2p destabilizes these elements, directly or indirectly, both to proofread
      spliceosome activation and to promote reconfiguration of the spliceosome to a
      fully competent, catalytic conformation. 

PMID- 24442616
TI  - Uptake and reduction of glycerate by isolated chloroplasts.
AB  - Intact chloroplasts of spinach (Spinacia oleracea L.) evolve O2 in the light in a
      glycerate-dependent reaction at rates usually close to 10 MUmolxmg(-1)
      chlorophyllxh(-1). Glycerate isfirst phosphorylated and the resulting
      phosphoglycerate reduced to the sugar level. Products of the reaction are the
      intermediates of the Calvin cycle and glycolate. The ratio of triosephosphates to
      phosphoglycerate is higher under low light or at a low pH than under high light
      or at a high pH. Chloroplasts contain activities of glycerate kinase which
      approximately correspond to observed glycerate reduction rates at light
      saturation. The main part of the glycerate kinase of leaf cells is localized in
      the chloroplasts, but considerable activity also resides outside these
      organelles. Glycerate can enter intact chloroplasts of spinach as the anion and
      the undissociated acid. It can thus mediate indirect proton transfer across the
      chloroplast envelope. In the presence of slowly permeating cations it is taken up
      mainly in an anion exchange reaction. Chloride and acetate anions permeate faster
      than the glycerate anion. The relation between glycerate reduction and
      photorespiration is discussed. 

PMID- 24442617
TI  - Amino acid permeability of the chloroplast envelope as measured by light
      scattering, volumetry and amino acid uptake.
AB  - The amino acid permeability of the envelope of intact, functional spinach
      (Spinacia oleracea L.) chloroplasts was investigated by light scattering,
      volumetry and uptake of (14)C-labelled amino acids. The criterion for the
      functionally of the chloroplasts was their ability to reduce CO2, PGA and
      oxaloacetate in the light at high rates.Net uptake into the chloroplast interior
      of neutral amino acids such as alanine, glycine, serine, proline, threonine or
      valine occurred only at very low rates. The uptake was concentration dependent,
      indicating unspecific diffusion rather than carrier-mediated transport. The
      slowness of uptake is emphasized by the capability of neutral amino acids to
      provide osmotic support for intact chloroplasts during a considerable length of
      time. Back-exchange experiments also failed to indicate the existence of specific
      exchange carriers for the transport of neutral amino acids such as alanine or
      glycine through the envelope of intact chloroplasts. Dicarboxylic amino-acids are
      known to be taken up by the so-called dicarboxylate translocator. The same
      carrier was found to catalyze also the transfer of asparagine and glutamine.The
      data do not support current assumptions concerning fast carrier-mediated
      transport of neutral amino acids and their role in the transfer of carbon during
      photosynthesis. 

PMID- 24442618
TI  - The effect of chilling on ethylene production, membrane permeability and water
      loss of leaves of Phaseolus vulgaris.
AB  - When seedlings of Phaseolus vulgaris L. vv. Canadian Wonder are chilled at 5
      degrees C (45% relative humidity) (RH), the primary leaves lose fresh weitht,
      produce ethylene at an increased rate when transferred to 25 degrees C and leak
      electrolytes at an increased rate when placed in water.Similar changes result
      from chilling excised leaves at 5 degrees C 20% RH. However, chilling only leads
      to increased rates of electrolyte leakage in partially dehydrated leaves.
      Chilling alone or water deficits alone (up to 30% fresh weight loss) do not lead
      to increased leakage.In contrast fresh weight loss alone does lead to an
      increased rate of ethylene production. Although a similar potential for increased
      ethylene production at 25 degrees C initially results from partial dehydration in
      both chilled and non-chilled leaves, this potential is maintained for longer at 5
      degrees C than at 25 degrees C. 

PMID- 24442619
TI  - Transfer of algal chloroplasts into protoplasts of higher plants.
AB  - Polyethylene-glycol treatment of mixed suspensions of isolated protoplasts and of
      chloroplasts induces chloroplast uptake by the protoplasts. Chloroplasts of algal
      origin (Vaucheria dichotoma (L.) Ag.) were transferred with high frequency into
      protoplasts of Daucus carota L. 

PMID- 24442621
TI  - Erratum.

PMID- 24442620
TI  - Cytochemical localization of phosphatase in barley aleurone cells: The pathway of
      gibberellic-acid-induced enzyme release.
AB  - Acid phosphatase has been localized by cytochemical techniques in aleurone layers
      of dry barley (Hordeum vulgare L.) grains, in imbibed half-grains and in isolated
      layers treated with and without gibberellic acid (GA3). A major fraction of the
      enzyme activity is located in the cell walls. During imbibition and incubation of
      layers without GA3 a steady increase of enzyme activity in the inner wall region
      indicates a continued release of enzyme into the walls, but there is no essential
      change in the distribution of wall-enzyme sites. On the other hand, when GA3 is
      present enzyme activity is found for the first time in regions of the wall that
      become digested during GA3 treatment. These results indicate that the digested
      wall channels act as preferential routes through which acid phosphatase is
      released from the aleurone layer. No digested wall channels are formed in the
      absence of GA3 and, there being no route for release of the enzyme, it
      accumulates in the inner regions of the wall around aleurone cells. Assays of
      enzyme activity in vitro support the conclusions based on the histochemical data.
      They indicate that release of acid phosphatase from aleurone layers is under
      strict GA3 control, but that some of the increase in acid phosphatase activity in
      the isolated during incubation is not GA3 dependent.Acid phosphatase is present
      in the protein matrix of aleurone grains in all stages except the dry grain.
      Enzyme activity persists in aleurone grains throughout GA3 treatment when
      enlargement of the grains and mobilization of reserves takes place. It is
      suggested that this phosphatase hydrolyses phosphate reserves within the aleurone
      grains. 

PMID- 24442622
TI  - Vitamin D status, functional decline, and mortality in peripheral artery disease.
AB  - Associations of vitamin D levels with prospectively measured functional decline
      and mortality in people with lower extremity peripheral artery disease (PAD) are
      unknown. We determined whether lower baseline vitamin D levels are associated
      with a faster decline in functional performance and higher mortality among people
      with and without PAD. A total of 658 participants (395 with PAD) underwent
      baseline measurement of 25-hydroxyvitamin D (DiaSorin radioimmunoassay), a 6
      minute walk test, 4-meter walking velocity and the Short Physical Performance
      Battery (SPPB), and were followed annually for up to 4 years. Analyses were
      adjusted for age, sex, race, body mass index, comorbidities, the ankle-brachial
      index, and other confounders. Among participants with PAD, lower baseline vitamin
      D levels were associated with a faster decline in the 6-minute walk (vitamin D <
      30 nmol/L: -70.0 feet/year; vitamin D 30 to < 50 nmol/L: -72.3 feet/year; vitamin
      D 50 to < 75 nmol/L: -35.5 feet/year; vitamin D 75 to < 120 nmol/L: -35.9
      feet/year; p trend=0.012). PAD participants with vitamin D < 30 nmol/L had a
      faster decline in the SPPB and 6-minute walk compared to those with levels of 50
      to < 75 (p=0.034 and p=0.04, respectively). Among participants without PAD, lower
      vitamin D was associated with a faster decline in the fast 4-meter walking
      velocity (p trend=0.003). There were no significant associations of baseline
      vitamin D levels with all-cause or cardiovascular disease mortality in PAD or non
      PAD participants. In conclusion, among individuals with and without PAD, low
      vitamin D status was associated with a faster decline in some measures of
      functional performance but was not related to mortality. 

PMID- 24442623
TI  - Neurochemical correlates of caudate atrophy in Huntington's disease.
AB  - The precise pathogenic mechanisms of Huntington's disease (HD) are unknown but
      can be tested in vivo using proton magnetic resonance spectroscopy ((1)H MRS) to
      measure neurochemical changes. The objective of this study was to evaluate
      neurochemical differences in HD gene mutation carriers (HGMCs) versus controls
      and to investigate relationships among function, brain structure, and
      neurochemistry in HD. Because previous (1)H MRS studies have yielded varied
      conclusions about HD neurochemical changes, an additional goal was to compare two
      (1)H MRS data analysis approaches. HGMCs with premanifest to early HD and
      controls underwent evaluation of motor function, magnetic resonance imaging, and
      localized (1)H MRS in the caudate and the frontal lobe. Analytical approaches
      that were tested included absolute quantitation (unsuppressed water signal as an
      internal reference) and relative quantification (calculating ratios of all
      neurochemical signals within a voxel). We identified a suite of neurochemicals
      that were reduced in concentration proportionally to loss of caudate volume in
      HGMCs. Caudate concentrations of N-acetylaspartate (NAA), creatine, choline, and
      caudate and frontal lobe concentrations of glutamate plus glutamine (Glx) and
      glutamate were correlated with caudate volume in HGMCs. The relative, but not the
      absolute, quantitation approach revealed disease-related differences; the Glx
      signal was decreased relative to other neurochemicals in the caudate of HGMCs
      versus controls. This is the first study to demonstrate a correlation among
      structure, function, and chemical measures in HD brain. Additionally, we
      demonstrate that a relative quantitation approach may enable the magnification of
      subtle differences between groups. Observation of decreased Glx suggests that
      glutamate signaling may be disrupted relatively early in HD, which has important
      implications for therapeutic approaches.

PMID- 24442624
TI  - Does nodal status influence survival? Results of a 19-year systematic
      lymphadenectomy experience during lung metastasectomy of colorectal cancer.
AB  - OBJECTIVES: Resection of pulmonary metastases originating from colorectal cancer
      is increasingly considered. While several adverse risk factors for long-term
      outcome are known, the selection of patients who may benefit from surgery remains
      unclear. In particular, few studies have addressed the impact of lymph node
      involvement, and signification of the hilar or mediastinal level of extent.
      METHODS: We retrospectively reviewed the data of 320 patients operated in two
      thoracic departments between 1992 and 2011. Appropriate statistical tests were
      used to compare groups at risk. RESULTS: There were 105 women and 215 men with a
      mean age of 63.3 years (range: 27-86) at the time of metastasectomy. Lymph node
      involvement appeared as a significant prognostic factor in both the univariate
      and multivariate analyses [median survival: 94 months N0 vs 42 months N+, P <
      0.0001; OR = 0.573 (0.329-1), P = 0.05]. Survival was similar for hilar and
      mediastinal locations (median survival: 47 months vs 37 months, respectively, P =
      0.14). Associated hepatic metastases had a negative impact on survival in both
      univariate and multivariate analyses [median survival: 74 months vs 47 months, P
      < 0.01; OR = 0.387 (0.218-0.686), P = 0.001]. Multiple lung metastases
      significantly decreased survival in univariate analysis only (median survival: 81
      months vs 55 months, P < 0.01). Disease-free survival and preoperative
      carcinoembryonic antigen had no impact on survival. CONCLUSIONS: While lymph node
      involvement was associated with decreased survival, the impact of mediastinal
      location on survival did not differ from that of hilar location. Consequently,
      these patients should not be excluded from surgical treatment.

PMID- 24442625
TI  - New HER2-positive targeting agents in clinical practice.
AB  - Overexpression of human epidermal growth factor occurs in approximately 20-25 %
      of invasive breast cancers. This subtype of breast cancer has been associated
      with poor clinical outcomes. The development of trastuzumab, a humanized
      monoclonal antibody that binds to the extracellular domain of human epidermal
      growth factor receptor 2 (HER2), revolutionized outcomes of patients with HER2
      positive breast cancer; however, many patients with HER2-positive metastatic
      breast cancer eventually become resistant to it. Several newer anti-HER2 agents
      have been developed, including lapatinib, pertuzumab, and trastuzumab emtansine.
      These exciting advances in drug development for HER2-positive breast cancer have
      also led to many challenges, including how to optimally sequence and combine HER2
      targeted agents. 

PMID- 24442626
TI  - Using problem-based learning to enhance the psychosocial competence of medical
      students.
AB  - This article provides an overview of adult learning principles and reviews their
      applicability and effectiveness in enhancing learner acquisition of psychosocial
      competencies. It presents a brief critique of traditional models of teaching
      medical students, reviews general principles of adult learning, describes the
      method of problem-based learning (PBL), summarizes data about outcomes of PBL,
      and suggests mechanisms through which PBL may enhance psychosocial learning. The
      author emphasizes the roles of small group interaction, exposure to diverse
      viewpoints, integrated presentation of psychosocial issues in cases, learning to
      adapt to uncertainty, and similarities with the process of psychotherapy as
      possible mediators for enhanced psychosocial learning through PBL. 

PMID- 24442627
TI  - Residency applicants in psychiatry : factors influencing program choice.
AB  - With the continued decline in the number of U.S. medical graduates entering
      psychiatry residencies and the possibility of a decrease in the number of funded
      psychiatry training positions in the near future, this study aimed to update our
      understanding of why applicants choose a residency program. For 5 years (1989
      1993), all applicants interviewed for postgraduate year-1 psychiatry positions at
      Long Island Jewish Medical Center/Hillside Hospital were asked to rank factors
      that influenced their program choice. The factors that were rated as most
      important, in declining order, were location (67.9%), reputation (46.2%),
      integration with a medical school (35.9%), resident satisfaction (33.2%), and
      quality of faculty (33.2%). 

PMID- 24442628
TI  - On the future of psychotherapy supervision in psychiatry.
AB  - Because psychotherapy supervision skills are learned primarily through experience
      as a psychotherapy supervisee, today's diminished training in psychodynamic
      psychotherapy can negatively influence future instruction in this important
      treatment modality. The author discusses role preparation for psychotherapy
      supervisors, suggests minimum standards for supervisor proficiency, and
      recommends ongoing instructional skills training. 

PMID- 24442629
TI  - A brief history of psychotherapy in graphic display.
AB  - Students of psychotherapy, faced with the variety of contemporary approaches, and
      their many major contributors, may find it difficult to see "the forest for the
      trees." If overwhelmed, they may uncritically limit their view to that provided
      by one or a few teachers, or even abandon the whole endeavor in favor of
      medication treatments. Three maps displaying a brief history of the
      psychotherapy, some of its major figures, and the primary contributors to 10
      current methods, are presented. Potential uses for these maps in student
      education are discussed. 

PMID- 24442630
TI  - Self-directed learning in a psychopathology course.
AB  - Self-directed learning has been identified as an essential element of
      professional development. In this approach, students receive in advance a
      complete set of objectives and didactic knowledge (cognitive) learning materials,
      are provided opportunities to develop skills with actual or simulated clinical
      experiences, and adapt a broad and flexible array of educational media to their
      individual learning styles. In the development of a self-directed psychopa
      thology course for second-year medical students, the authors incorporated four
      modifications to the traditional lecture and small group (faculty-directed)
      approach: 1) independent (self-directed) learning with no prescribed study times
      or sequence to the material, 2) use of student and facult y-directed interviews
      of patients, 3) greater freedom for selecting teaching methods in small groups,
      and 4) elimination of formal lectures. The authors describe the educational
      results with such an approach. 

PMID- 24442632
TI  - Availability and use of dual energy X-ray absorptiometry (DXA) and bio-impedance
      analysis (BIA) for the evaluation of sarcopenia by Belgian and Latin American
      geriatricians.

PMID- 24442633
TI  - High-Field iMRI in transsphenoidal pituitary adenoma surgery with special respect
      to typical localization of residual tumor.
AB  - BACKGROUND: Intraoperative high-field magnetic resonance imaging (iMRI) is used
      as an immediate intraoperative quality control, evaluating the extent of tumor
      removal during the surgical procedure and allowing us to extend resections in
      those cases where tumor remnants are documented. The aim of the study was to
      analyze the typical localization of residual tumor remnants, detected by iMRI
      during transsphenoidal surgery of pituitary adenomas. METHODS: We reviewed a
      series of 72 patients. All patients presented with macroadenomas with or without
      suprasellar extension. After high-field MRI investigation, we divided the series
      preoperatively into totally resectable (TR) and non-totally resectable (NTR)
      tumors. Tumor remnants were documented by iMRI, obtained directly after tumor
      removal, as well as by intraoperative surgical inspection of the sellar content.
      RESULTS: In the TR group, we observed 23 cases suspicious for tumor remnants,
      located anteriorly, laterally, posteriorly, and suprasellar under descending
      folds of the diaphragm. Continuing surgery, upon a "second inspection", tumor
      resection could be completed in all cases. CONCLUSIONS: Incomplete removal of
      resectable pituitary adenomas could be avoided in a higher number of cases with
      the knowledge of the location of the typical remnant tumors. In those cases where
      it is not possible to achieve a complete resection of adenoma, further treatment
      can be planned at an earlier stage, without any need to wait for the conventional
      postoperative MRI scan performed 2 to 3 months after surgery.

PMID- 24442634
TI  - Will branch for food-nutrient-dependent tracheal remodeling in Drosophila.

PMID- 24442635
TI  - Developmental refinement of hair cell synapses tightens the coupling of Ca2+
      influx to exocytosis.
AB  - Cochlear inner hair cells (IHCs) develop from pre-sensory pacemaker to sound
      transducer. Here, we report that this involves changes in structure and function
      of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around
      hearing onset in mice. As synapses matured they changed from holding several
      small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to
      one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had
      fewer and larger ribbons; (ii) CaV1.3 channels formed stripe-like clusters rather
      than the smaller and round clusters at immature AZs; (iii) extrasynaptic CaV1.3
      channels were selectively reduced, (iv) the intrinsic Ca(2)(+) dependence of fast
      exocytosis probed by Ca(2)(+) uncaging remained unchanged but (v) the apparent
      Ca(2)(+) dependence of exocytosis linearized, when assessed by progressive
      dihydropyridine block of Ca(2)(+) influx. Biophysical modeling of exocytosis at
      mature and immature AZ topographies suggests that Ca(2)(+) influx through an
      individual channel dominates the [Ca(2)(+)] driving exocytosis at each mature
      release site. We conclude that IHC synapses undergo major developmental
      refinements, resulting in tighter spatial coupling between Ca(2)(+) influx and
      exocytosis. 

PMID- 24442636
TI  - Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity
      at a CNS synapse.
AB  - Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory
      information at hundreds per second to bushy cells (BCs) in the anteroventral
      cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb
      synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced
      ANF input into the AVCN. Endbulb terminals and active zones were normal in number
      and vesicle complement. Postsynaptic densities, quantal size and vesicular
      release probability were increased while vesicle replenishment and the standing
      pool of readily releasable vesicles were reduced. These opposing effects canceled
      each other out for the first evoked EPSC, which showed unaltered amplitude. We
      propose that ANF activity deprivation drives homeostatic plasticity in the AVCN
      involving synaptic upscaling and increased intrinsic BC excitability. In vivo
      recordings from individual mutant BCs demonstrated a slightly improved response
      at sound onset compared to ANF, likely reflecting the combined effects of ANF
      convergence and homeostatic plasticity. Further, we conclude that bassoon
      promotes vesicular replenishment and, consequently, a large standing pool of
      readily releasable synaptic vesicles at the endbulb synapse. 

PMID- 24442638
TI  - It's not over until the FAT lady sings.

PMID- 24442637
TI  - A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in
      extrinsic apoptosis.
AB  - The extrinsic apoptosis pathway is initiated by binding of death ligands to death
      receptors resulting in the formation of the death-inducing signaling complex
      (DISC). Activation of procaspase-8 within the DISC and its release from the
      signaling complex is required for processing executor caspases and commiting cell
      death. Here, we report that the atypical cadherin FAT1 interacts with caspase-8
      preventing the association of caspase-8 with the DISC. We identified FAT1 in a
      genome-wide siRNA screen for synthetic lethal interactions with death receptor
      mediated apoptosis. Knockdown of FAT1 sensitized established and patient-derived
      glioblastoma cell lines for apoptosis transduced by cell death ligands. Depletion
      of FAT1 resulted in enhanced procaspase-8 recruitment to the DISC and increased
      formation of caspase-8 containing secondary signaling complexes. In addition,
      FAT1 knockout cell lines generated by CRISPR/Cas9-mediated genome engineering
      were more susceptible for death receptor-mediated apoptosis. Our findings provide
      evidence for a mechanism to control caspase-8-dependent cell death by the
      atypical cadherin FAT1. These results contribute towards the understanding of
      effector caspase regulation in physiological conditions. 

PMID- 24442639
TI  - TopBP1 deficiency impairs V(D)J recombination during lymphocyte development.
AB  - TopBP1 was initially identified as a topoisomerase II-beta-binding protein and it
      plays roles in DNA replication and repair. We found that TopBP1 is expressed at
      high levels in lymphoid tissues and is essential for early lymphocyte
      development. Specific abrogation of TopBP1 expression resulted in transitional
      blocks during early lymphocyte development. These defects were, in major part,
      due to aberrant V(D)J rearrangements in pro-B cells, double-negative and double
      positive thymocytes. We also show that TopBP1 was located at sites of V(D)J
      rearrangement. In TopBP1-deficient cells, gamma-H2AX foci were found to be
      increased. In addition, greater amount of gamma-H2AX product was precipitated
      from the regions where TopBP1 was localized than from controls, indicating that
      TopBP1 deficiency results in inefficient DNA double-strand break repair. The
      developmental defects were rescued by introducing functional TCR alphabeta
      transgenes. Our data demonstrate a novel role for TopBP1 as a crucial factor in
      V(D)J rearrangement during the development of B, T and iNKT cells. 

PMID- 24442640
TI  - Redesigning the procaspase-8 dimer interface for improved dimerization.
AB  - Caspase-8 is a cysteine directed aspartate-specific protease that is activated at
      the cytosolic face of the cell membrane upon receptor ligation. A key step in the
      activation of caspase-8 depends on adaptor-induced dimerization of procaspase-8
      monomers. Dimerization is followed by limited autoproteolysis within the
      intersubunit linker (IL), which separates the large and small subunits of the
      catalytic domain. Although cleavage of the IL stabilizes the dimer, the uncleaved
      procaspase-8 dimer is sufficiently active to initiate apoptosis, so dimerization
      of the zymogen is an important mechanism to control apoptosis. In contrast, the
      effector caspase-3 is a stable dimer under physiological conditions but exhibits
      little enzymatic activity. The catalytic domains of caspases are structurally
      similar, but it is not known why procaspase-8 is a monomer while procaspase-3 is
      a dimer. To define the role of the dimer interface in assembly and activation of
      procaspase-8, we generated mutants that mimic the dimer interface of effector
      caspases. We show that procaspase-8 with a mutated dimer interface more readily
      forms dimers. Time course studies of refolding also show that the mutations
      accelerate dimerization. Transfection of HEK293A cells with the procaspase-8
      variants, however, did not result in a significant increase in apoptosis,
      indicating that other factors are required in vivo. Overall, we show that
      redesigning the interface of procaspase-8 to remove negative design elements
      results in increased dimerization and activity in vitro, but increased
      dimerization, by itself, is not sufficient for robust activation of apoptosis. 

PMID- 24442641
TI  - Mutational patterns in the breast cancer mitochondrial genome, with clinical
      correlates.
AB  - The presence of mitochondrial DNA (mtDNA) mutations in human cancer has long been
      recognized, but their functional significance has remained obscure. Debate
      persists as to whether the mutations help drive the tumor, or are bystander
      events. Here, we analyze next-generation mtDNA sequence data from 99 breast
      cancer patients. High depth coverage enables detection of even low-level
      heteroplasmic variants, and data from matched normal tissue allow us to
      distinguish between shifts in heteroplasmy and acquired mutations. Somatic mtDNA
      mutations are found in 73 (73.7%) of patient tumors, and dramatic shifts from the
      initial germline allele proportions are observed for many heteroplasmies.
      Clustering of somatic mutations in promoter and replication regions, and also in
      genes coding for electron transport chain complex I, suggest selection for
      mutations affecting critical mitochondrial processes. Furthermore, statistical
      tests for Darwinian selection reveal evidence for positive and relaxed negative
      selection for somatic missense mutations. We also observe a dramatic decrease in
      per-cell mtDNA content in tumor tissues, as well as a surprising positive
      correlation between somatic mtDNA mutational burden and patient survival. Taken
      together, our results support the view that somatic mtDNA mutations are not
      solely bystander events, but have significance in cancer from both biological and
      clinical perspectives. We also anticipate that the catalog of heteroplasmies and
      somatic mutations presented here will serve as a reference for future studies of
      cancer mitochondrial genomes. 

PMID- 24442643
TI  - Treatment and outcomes in diabetic breast cancer patients.
AB  - Effective breast cancer management is more complex with diabetes present and may
      contribute to poor outcomes. Therefore, we conducted two simultaneous systematic
      reviews to address the association of diabetes with (1) treatment patterns in
      breast cancer patients and (2) breast cancer recurrence rates or breast cancer
      specific and all-cause mortality. We searched major databases for English
      language peer-reviewed studies through November 2013, which addressed either of
      the above research questions, following the preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) method. Analyses compared treatment
      patterns or health outcomes for breast cancer subjects with and without diabetes.
      We used STROBE quality criteria and conducted a random-effects meta-analysis of
      all-cause mortality. The review yielded 11 publications for question 1 and 26 for
      question 2, with nine overlapping. Treatment studies showed chemotherapy was less
      likely in patients with diabetes. Of 22 studies, 21 assessing all-cause mortality
      indicated a statistically significant increased overall mortality for patients
      with diabetes (hazard ratios: 0.33-5.40), with meta-analysis of eligible studies
      indicating a 52 % increased risk. Nine studies assessing breast cancer-specific
      mortality had inconsistent results, with five showing significantly increased
      risk for diabetes patients. Results were inconsistent for recurrence and
      metastases. The majority of studies reported detrimental associations between
      diabetes and optimal treatment or all-cause mortality among women with breast
      cancer. Divergence in variable and outcomes inclusion and definitions, potential
      participation bias in individual studies, and differing analytic methods make
      inferences difficult. This review illuminates the importance of the impact of
      diabetes on breast cancer patients and explicitly recognizes that co-management
      of conditions is necessary to prevent excess morbidity and mortality.

PMID- 24442642
TI  - Circulating estrogens and estrogens within the breast among postmenopausal
      BRCA1/2 mutation carriers.
AB  - Accurately quantifying parent estrogens (PE) estrone (E1) and estradiol (E2) and
      their metabolites (EM) within breast tissue and serum may permit detailed
      investigations of their contributions to breast carcinogenesis among BRCA1/2
      mutation carriers. We conducted a study of PE/EM in serum, nipple aspirate fluid
      (NAF), and ductal lavage supernatant (DLS) among postmenopausal BRCA1/2 mutation
      carriers. PE/EM (conjugated and unconjugated) were measured in paired serum/NAF
      (n = 22 women) and paired serum/DLS samples (n = 24 women) using quantitative
      liquid chromatography-tandem mass spectrometry (LC/MS/MS). The relationships
      between serum and tissue-specific PE/EM were measured using Pearson's correlation
      coefficients. Conjugated forms of PE/EM constituted the majority of estrogen in
      serum (88 %), NAF (59 %) and DLS (69 %). PE/EM in NAF and serum were highly
      correlated [E1 (r = 0.97, p < 0.0001), E2 (r = 0.90, p < 0.0001) and estriol (E3)
      (r = 0.74, p < 0.0001)] as they were in DLS and serum [E1 (r = 0.92, p < 0.0001;
      E2 (r = 0.70, p = 0.0001; E3 (r = 0.67, p = 0.0004)]. Analyses of paired total
      estrogen values for NAF and serum, and DLS and serum yielded ratios of 0.22 (95 %
      CI 0.19-0.25) and 0.28 (95 % CI 0.24-0.32), respectively. This report is the
      first to employ LC/MS/MS to quantify PE/EM in novel breast tissue-derived
      biospecimens (i.e., NAF and DLS). We demonstrate that circulating PE and EM are
      strongly and positively correlated with tissue-specific PE and EM measured in NAF
      and DLS among postmenopausal BRCA1/2 mutation carriers. If confirmed, future
      etiologic studies could utilize the more readily obtainable serum hormone levels
      as a reliable surrogate measure of exposure at the tissue level.

PMID- 24442644
TI  - The role of Sudanese community pharmacists in patients' self-care.
AB  - OBJECTIVES: To describe the current and potential roles of Sudanese community
      pharmacists in responding to symptoms (RTS) and chronic diseases management (CDM)
      and identify perceived barriers. SETTINGS: Community pharmacies in Khartoum
      State. METHOD: A structured, self-administered, piloted questionnaire was
      conducted of pharmacists in charge of 274, randomly selected, community
      pharmacies. Close ended questions and a 5-point Likert-type scale were used to
      measure responses. MAIN OUTCOME MEASURE: Respondents' demographics, their current
      activities, attitude and involvement in RTS and CDM and potential barriers.
      Response rate was 67 %. The majority of respondents (>90 %) reported that they
      are involved in RTS activities but have negative views regarding practice
      standards. They lack specific lists of minor conditions and their treatment (87.4
      %), recorded counseling procedure (84.7 %), and referral forms (85.8 %). Almost
      all community pharmacists see an important role for them in CDM (4.54 +/- 0.74,
      95.3 %) and accept team work with other health care providers (4.46 +/- 0.74,
      87.5 %). Lack of proper knowledge and training, time, space, patients' acceptance
      and official recognition of pharmacists' new role, were some of the identified
      barriers. CONCLUSION: Sudanese community pharmacists provide RTS and CDM
      services; however, clinical knowledge and training and well defined national
      practice standards needs were identified. The current product-focused activities
      need to be refined to include more patient-focused services. For Improved
      patients' self-care services, a number of obstacles identified by surveyed
      pharmacists need to resolved. This requires collaboration of different parties
      including academics, governmental bodies and professional organizations.

PMID- 24442645
TI  - Correlation between laryngeal sensitivity and penetration/aspiration after
      stroke.
AB  - Stroke is the most common neurological disease in adults that is associated with
      deglutition disorders. The presence of laryngeal sensitivity is very important in
      developing safe swallowing without risk of pulmonary complications. The aim of
      this study was to correlate laryngeal sensitivity with laryngeal penetration and
      tracheal aspiration after swallows of three food consistencies (puree, thickened
      liquid, and liquid) in poststroke individuals in the late phase. A cross
      sectional clinical study was performed with 91 post-ischemic stroke individuals,
      with oropharyngeal dysphagia, who were in rehabilitation center treatment from
      2009 to 2011. They had a mean age of 68.1 years and average time since injury was
      22.6 months; 39 had injury to the right hemisphere and 52 had injury to the left
      hemisphere. All underwent fiberoptic endoscopic evaluation of swallowing and
      evaluation of laryngeal sensitivity by touching the tip of the endoscope to the
      arytenoids and aryepiglottic folds. The linear correlation coefficient of
      Spearman was applied to evaluate the correlation between laryngeal penetration
      and tracheal aspiration and the presence/absence of laryngeal sensitivity. There
      was a negative correlation between the observation of penetration and tracheal
      aspiration and laryngeal sensitivity, with all bolus consistencies (p < 0.001 for
      aspiration and p <= 0.01 for penetration). The absence of laryngeal sensitivity
      determines the more frequent findings of penetration and tracheal aspiration.
      This sensory stimulus in the mucosa of the pharynx and larynx is an essential
      element for safe swallowing and its deficiency associated with altered motor
      activity can cause laryngeal penetration and aspiration in poststroke individuals
      regardless of food consistency. 

PMID- 24442646
TI  - Osteoinductivity of gelatin/beta-tricalcium phosphate sponges loaded with
      different concentrations of mesenchymal stem cells and bone morphogenetic protein
      2 in an equine bone defect model.
AB  - Fracture is one of the most life-threatening injuries in horses. Fracture repair
      is often associated with unsatisfactory outcomes and is associated with a high
      incidence of complications. This study aimed to evaluate the osteogenic effects
      of gelatin/beta-tricalcium phosphate (GT) sponges loaded with different
      concentrations/ratios of mesenchymal stem cells (MSCs) and bone morphogenetic
      protein-2 (BMP-2) in an equine bone defect model. Seven thoroughbred horses were
      used in this study. Eight bone defects were created in the third metatarsal bones
      of each horse. Then, eight treatments, namely control, GT, GT/M-5, GT/M-6, GT/M
      5/B-1, GT/M-5/B-3, GT/M-6/B-1, and GT/M-6/B-3 were applied to the eight different
      sites in a randomized manner (M-5: 2 * 10(5) MSCs; M-6: 2 * 10(6) MSCs; B-1: 1
      MUg of BMP-2; B-3: 3 MUg of BMP-2). Repair of bone defects was assessed by
      radiography, quantitative computed tomography (QCT), and histopathological
      evaluation. Radiographic scores and CT values were significantly lower in the
      control group than in the other groups, while they were significantly higher in
      the GT/M-5/B-3 and GT/M-6/B-3 groups than in the other groups. The amount of
      mature compact bone filling the defects was greater in the GT/M-5/B-3 and GT/M
      6/B-3 groups than in the other groups. The present study demonstrated that the GT
      sponge loaded with MSCs and BMP-2 promoted bone regeneration in an equine bone
      defect model. The GT/MSC/BMP-2 described here may be useful for treating horses
      with bone injuries.

PMID- 24442649
TI  - Indolyl-3-acetic acid in cap and apex of maize roots: Identification and
      quantification by mass fragmentography.
AB  - Quantitative analysis of indolyl-3-acetic acid (IAA) in different parts of maize
      root tips (Zea mays L. cv. Kelvedon 33) were performed by selective ion current
      monitoring detection (or mass fragmentography). It was found that the cap
      contained 356.6+/-16.2 MUg of IAA kg(-1) fresh weight; the apex had only half
      this concentration of IAA. Calculations indicated that the 10-mm apical segments
      of the root contained 109.6 MUg kg(-1) fresh weight. The possibility that the
      growth regulator formed in the cap and inhibiting the elongation of the extension
      zone of the root is IAA is discussed. 

PMID- 24442648
TI  - Volume control in treatment-resistant congestive heart failure: role for
      peritoneal dialysis.
AB  - Chronic congestive heart failure (HF) has a rising prevalence and increasing
      impact on health care systems. Current treatment consists of diuretics, renin
      angiotensin-aldosterone system blockers, and restriction of salt and fluids. This
      strategy is often hampered by a drop in effective circulating volume and hence
      renal perfusion and function, triggering harmful counter regulatory mechanisms.
      Slow ultrafiltration by peritoneal dialysis (PD) might be an effective treatment
      strategy to relieve fluid overload without compromising cardiac output and
      thereby renal function. In this review, we discuss the (patho)physiological
      mechanisms of the cardiorenal interaction and the current literature on PD
      strategies in congestive HF. 

PMID- 24442647
TI  - Auditory brainstem responses in Cope's gray treefrog (Hyla chrysoscelis): effects
      of frequency, level, sex and size.
AB  - Our knowledge of the hearing abilities of frogs and toads is largely defined by
      work with a few well-studied species. One way to further advance comparative work
      on anuran hearing would be greater use of minimally invasive electrophysiological
      measures, such as the auditory brainstem response (ABR). This study used the ABR
      evoked by tones and clicks to investigate hearing in Cope's gray treefrog (Hyla
      chrysoscelis). The objectives were to characterize the effects of sound
      frequency, sound pressure level, and subject sex and body size on ABRs. The ABR
      in gray treefrogs bore striking resemblance to ABRs measured in other animals. As
      stimulus level increased, ABR amplitude increased and latency decreased, and for
      responses to tones, these effects depended on stimulus frequency. Frequency
      dependent differences in ABRs were correlated with expected differences in the
      tuning of two sensory end organs in the anuran inner ear (the amphibian and
      basilar papillae). The ABR audiogram indicated two frequency regions of increased
      sensitivity corresponding to the expected tuning of the two papillae. Overall,
      there was no effect of subject size and only small effects related to subject
      sex. Together, these results indicate the ABR is an effective method to study
      audition in anurans. 

PMID- 24442651
TI  - Changes in specific radioactivities of sunflower leaf metabolites during
      photosynthesis in (14)CO 2 and (12)CO 2 at normal and low oxygen.
AB  - Sunflower (Helianthus annuus L.) leaf discs were exposed to (14)CO2 or (14)CO2
      followed by (12)CO2 in an open gas-exchange system with incoming gas of
      approximately 400 ppm CO2 and either 21% or 1% O2. The (14)CO2 and (12)CO2 gas
      exchange of the leaf discs were measured, and the specific activities of several
      metabolites were determined after different lengths of time. The rate of CO2
      efflux by the leaf discs was ca. 20% of the net photosynthetic rate at 21% O2 but
      no CO2 efflux could be detected at 1% O2. At both O2 concentrations the specific
      activity of 3-phosphoglyceric acid (3-PGA) increased and decreased rapidly for
      the first 5 min, and then more slowly during (14)CO2 feeding and (12)CO2
      flushing. At 21% O2, glycine, serine and alanine changed more slowly in specific
      activity than 3-PGA and at 1% O2 their specific activities were much lower than
      at 21% O2. The results at both O2 concentrations indicated that the glycolate
      pathway compounds were not derived solely from Calvin-cycle intermediates. At 1%
      O2 the flux of carbon from the immediate fixation products was inhibited and
      serine was at least partially produced from a precursor of higher specific
      activity than glycine, although the glycolate pathway may have been active even
      at 1% O2. The difference between the specific activities of 3-PGA and the feeding
      gases could be explained by the recycling of C from the glycolate pathway. 

PMID- 24442650
TI  - Changes in specific radioactivities of corn-leaf metabolites during
      photosynthesis in (14)CO 2 and (12)CO 2 at normal and low oxygen.
AB  - The (12)CO2- and (14)CO2-exchange of illuminated corn leaf discs were measured at
      normal (21%) and low (1%) oxygen. After periods of exposure to (14)CO2 or to
      (14)CO2 followed by (12)CO2, the discs were killed and the specific activities of
      some metabolites were determined. At both O2 concentrations the specific activity
      of 3-PGA increased and decreased rapidly during the first 5 min of (14)CO2
      feeding or (12)CO2-flushing but did not equilibrate with that of the CO2 in the
      assimilation chamber even after 15 min. The specific activity of aspartic acid
      also showed bimodal kinetics during both feeding and flushing. The specific
      activities of 3-phosphoglyceric acid (3-PGA), aspartic acid and alanine were
      higher at 1% O2 than at 21% O2, but glycine and serine were lower in specific
      activity at 1% O2. The results are in agreement with the proposed initial
      fixation of CO2 into C4-dicarboxylic acids and subsequent transfer of this carbon
      to 3-PGA. Indirect evidence supports the idea that at 21% O2, CO2 was produced by
      the corn leaf discs in the light and was refixed into C4-dicarboxylic acids. At
      1% O2, the photorespiratory process could also have been active although the flux
      of carbon through the glycolate pathway was probably smaller than at 21% O2. 

PMID- 24442652
TI  - [Growth and synchronization of cell division in the alga Bumilleriopsis
      filiformis].
AB  - 1. Axenic cultures of Bumilleriopsis were cultivated in mineral medium under
      continuous illumination and diluted every two days. The growth has been
      calculated to be 0.50 log10/day units at the optimum temperature of 23 to 24
      degrees  C. 2. In liquid medium one cell normally divides into 2(n) daughter
      cells (=aplanospores). Under our culture conditions generally 8 and 16 daughter
      cells are produced by one Bumilleriopsis cell within 48 h. 3. Bumilleriopsis
      filiformis is the first Xanthophycean species to be synchronized. Light-dark
      changes induce some synchronization, but a high percentage of simultaneous
      division and rapid completion of a cell division burst is brought about most
      effectively by cycles composed of strong light/dim light/temperature changes (LS
      T). With the most effective combination tested, i.e. 33 h of white 15000 lux
      light followed by 15 h of white 3000 lux (dim) light at temperatures of 24
      degrees  in the first and 19 degrees  C in the second light phase (=33:15
      h/15000:3000 lux/24:19 degrees  C), 96% of the cells divide synchronously. The
      burst occurs in such a manner that, on an average, 50% of the cells have divided
      38 h after the start of the cycle. These synchronizing conditions were maintained
      up to 30 cycles without interruption (=continuous synchronization). 4. Cell wall
      formation is observed (by staining mother cells with methylene blue) 1 to 2 h
      before the cells divide completely and their daughter cells are released. 

PMID- 24442653
TI  - Separation and characterization of two inorganic pyrophosphatases from spinach
      leaves.
AB  - Two inorganic pyrophosphatases (pyrophosphate phosphohydrolase, E.C.3.6.1.1) have
      been identified in spinach (Spinacia oleracea L.) leaves. The two isoenzymes were
      readily separated by polyacrylamide gel electrophoresis and by isoelectric
      focusing between pH 4 and 6. One isoenzyme is located in the chloroplasts whereas
      the other form was isolated from the soluble "cytoplasmic" fraction. In addition,
      a third form appeared when the isolation procedure started from a crude extract
      from whole leaves. It is suggested that this form represents an aggregation
      between the two natural species.The three forms differ in their kinetic
      properties, such as substrate affinity and pH optima. The apparent K m values
      were determined to be 10(-5)M for the chloroplastic isoenzyme, 7*10(-5) M for the
      "cytoplasmic" isoenzyme and 3*10(-5) M for the third form. At limiting Mg(2+)
      concentrations, the corresponding pH optima were found to be 8.55, 8.95 and 8.75,
      respectively. 

PMID- 24442654
TI  - [The influence of starch on the activity of pyrophosphatase from isolated spinach
      chloroplasts].
AB  - The activity of the inorganic pyrophosphatase from isolated spinach (Spinacia
      oleracea L.) chloroplasts is strongly dependent upon the addition of magnesium
      ions. Since the complex of the bivalent ion with inorganic pyrophosphate is the
      real substrate, a definite Mg(2+)/Na4P2O7-ratio is required for maximum activity.
      When the activity was measured in particle-free extracts from chloroplasts, this
      ratio was shown to be approximately 3. However, an increase up to 10 was observed
      in the presence of thylakoid membranes. Furthermore, the kinetics in the presence
      of broken chloroplasts becomes sigmoidal.The altered kinetics have been shown to
      be due to starch located in the thylakoids. The inhibitory effect is caused by
      amylose alone but not by amylopectin., Detailed kinetic analysis of the
      inhibition showed no influence of amylose on the Hill-coefficient. Since
      ethylenediaminetetracetic acid was shown to have similar effects as amylose,
      starch might regulate the pyrophosphatase activity by binding Mg(2+)-ions. 

PMID- 24442655
TI  - Abscission in Phaseolus vulgaris the positional differentiation and ethylene
      induced expansion growth of specialised cells.
AB  - Cell separation in abscission zones of explants of Phaseolus vulgaris L. is
      preceded by the enlargement of a single row of cells. Unlike the other cells
      surrounding them, the cells of this row enlarge in response to ethylene and not
      to auxin.Enlargement follows an increase in the activity of carboxymethyl 1: 4
      glucanase in the abscission zone; also a response to ethylene and not to
      auxin.Eventual cell separation occurs between the enlarging cells and the non
      enlarging tissue distal to them.It is proposed that the formation of cells at the
      abscission zone, with growth properties dissimilar to those of the rest of the
      pulvinus and petiole, is an example of precise positional differentiation. The
      presence and enlargement of such cells may be a general prerequisite for the
      abscission of organs or tissues distal to them. 

PMID- 24442656
TI  - [Nuclear criteria for complete dormancy in the shoot apex of Fraxinus excelsior
      L].
AB  - The cytohistological criteria for the vegetative shoot apex dormancy in Fraxinus
      excelsior L. have been quantitatively established with the aid of 3 techniques:
      historadiography after incorporation of [(3)H]thymidine, mitotic index and
      nuclear cytophotometry by the two wavelength method. Nuclear DNA content, mitotic
      activity and DNA synthesis were compared in 3 different zones(apical zone,
      lateralzone, rib meristem) of the dormant and non-dormant apices. The periodical
      break in morphogenetic activity, in contrast to the vegetative period (April to
      July), is characterized by the absence of zonation and by the fact that
      meristematic cells remain in the G1 phase of the mitotic cycle. In Fraxinus
      excelsior L., the meristem dormancy is complete (no DNA synthesis, no mitotic
      activity and no DNA content greater than 2C). 

PMID- 24442657
TI  - Rubulose diphosphate carboxylase synthesis in Chlamydomonas reinhardii:
      Inhibition by chloramphenicol and stimulation by cycloheximide.
AB  - Chloramphenicol at 50 and 100 MUg/ml inhibited synthesis of ribulose diphosphate
      carboxylase in the ac-20 mutant strain of Chlamydomonas reinhardii. Cycloheximide
      at 0.5 and 1.0 MUg/ml significantly stimulated synthesis of this enzyme. By
      comparison, chloramphenicol had no effect on induction of isocitrate lyase by
      acetate, and cycloheximide completely inhibited this induction. The data suggest
      either that the carboxylase is made completely on 70S ribosomes or, less likely,
      that pools of subunit made on 80S ribosomes exist with long life times in the C.
      reinhardii cell. 

PMID- 24442658
TI  - [Dependence of membrane potential of Chlorella fusca on pH, temperature and
      light].
AB  - The dependence on external parameters of the membrane potential of Chlorella
      fusca (Shihira et Krauss) 211-8b, Gottingen, has been measured in media
      containing no salt except KCl. Near neutrality the potential is practically
      independent of pH. The negative potential increases with temperature from-12 mV
      at 5 degrees CC to-45 mV at 20 degrees , and remains constant thereafter, i.e.,
      at least up to 30 degrees . Upward temperature jumps of 5 degrees cause a fast
      hyperpolarisation, which is independent in magnitude of the starting temperature.
      The potential is influenced by illumination, and this effect increases with
      temperature. The light effect is reduced by 3-(3,4-dichlorophenyl)-1,1-dimethyl
      urea and practically abolished by carbonyl cyanide-m-chlorophenyl hydrazone. 

PMID- 24442659
TI  - Effects of N(6)-benzyladenine on the rate of turnover of [(3)H]GA 20 by shoots of
      dwarf Pisum sativum.
AB  - Application of the cytokinin, N(6)-benzyladenine, to light-grown shoots of dwarf
      "Meteor" pea seedlings (Pisum sativum L.) markedly increased the rate of turnover
      of GA20, a native pea gibberellin. It is suggested that endogenous cytokinins may
      affect gibberellin metabolism in plants by controlling rates of gibberellin
      turnover. 

PMID- 24442660
TI  - Isolation of nuclei from rice tissue grown in suspension culture.
AB  - A simple method is described for the isolation of intact nucleic from rice tissue
      (Oryza sativa L.) grown in suspension culture. The procedure involves incubation
      of the tissue for 4 h with cellulase and pectinase prior to disruption of the
      cells. The yield of nucleic is approximately 40% (DNA basis) and the preparations
      are capable of synthesizing RNA in vitro. The method may be valuable to
      biochemically oriented research requiring plant nuclei. 

PMID- 24442661
TI  - Changes in the enzyme pattern of greening tissue cultures of Nicotinana tabacum
      var. "Samsun".
AB  - In tissue cultures of Nicotiana tabacum L. ribulose-diphosphate carboxylase and
      NADP-dependent glyceraldehyde-3-phosphate dehydrogenase can be found only after
      transfer of the tissue to light. The increase of the activities of these enzymes
      parallels that of chlorophyll.The increase in ribulose-diphosphate carboxylase is
      not associated with a decrease in glucose-6-phosphate dehydrogenase activity as
      described for rye seedlings (Feierabend, Planta 71, 326-355, 1966). If
      chloramphenicol is added to the cultures before greening no ribulose diphosphate
      carboxylase activity can be found, whereas there is no effect on the activity of
      glucose-6-phosphate dehydrogenase. It is shown that glucose-6-phosphate
      dehydrogenase activity changes with the glucose concentration of the growth
      medium. 

PMID- 24442662
TI  - Accelerated endogenous growth in Avena coleoptile segments.
AB  - An unexpected acceleration in elongation of Avena coleoptile segments has been
      observed with a position sensor transducer 2 to 2.5 h after excision when the
      segments are immersed in 5 mM succinate buffer (pH 6). The cause of the
      accelerated growth is unknown. 

PMID- 24442664
TI  - Comparison of unfolding codes for neutron spectrometry with Bonner spheres.
AB  - This work compares the results of four different unfolding codes, MSANDB, MAXED,
      FRUIT and BONMA, which are based on different unfolding techniques. Additionally,
      Bayesian parameter estimation is also considered. All unfolding codes were
      supplied with the same set of input data acquired at the Environmental Research
      Station 'Schneefernerhaus' on the Zugspitze mountain, corresponding to continuous
      measurements of secondary neutrons from cosmic radiation. The HMGU high-energy
      extended Bonner sphere spectrometer (BSS), consisting of 16 measuring channels
      with (3)He proportional counters, was used as a reference BSS. The differences in
      the neutron spectra obtained with the different unfolding codes are discussed,
      and the uncertainties of integral quantities, like neutron fluence and ambient
      dose equivalent, are quantified. 

PMID- 24442663
TI  - Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict
      chemotherapeutic response and survival outcomes in metastatic advanced gastric
      cancer.
AB  - BACKGROUND: Several studies have shown that the neutrophil to lymphocyte ratio
      (NLR) in peripheral blood is a prognostic factor of various cancers. However,
      there is limited information on the clinical and prognostic significance of NLR
      in patients with metastatic advanced gastric cancer (AGC). Therefore, we examined
      whether the NLR can be used as a prognostic marker for predicting
      chemotherapeutic response and survival outcomes in metastatic AGC patients who
      are receiving palliative chemotherapy. METHOD: A total of 268 patients diagnosed
      with metastatic AGC were enrolled. NLR was calculated from complete blood cell
      count taken before the first chemotherapy treatment. Patients were divided into
      two groups according to the median value of NLR: a high NLR group and a low NLR
      group. RESULT: The median follow-up period was 340 days (range 72-1796 days) and
      median NLR was 3.06 (range 0.18-18.16). The high NLR group (NLR >3.0) contained
      138 patients and the low NLR group (NLR <=3.0) contained 130 patients. Low NLR
      group patients had a significantly higher chemotherapeutic disease control rate
      (90.0 % vs. 80.4; P = 0.028), and longer progression-free survival (PFS) and
      overall survival (OS) than the high NLR group patients (186 vs. 146 days; P =
      0.001; 414 vs. 280 days; P < 0.001, respectively). In multivariate analysis, NLR
      showed a significant association with PFS (HR 1.478; 95 % CI 1.154-1.892; P =
      0.002) and OS (HR 1.569; 95 % CI 1.227-2.006; P < 0.001). CONCLUSION:
      Pretreatment NLR is a useful prognostic marker in patients with metastatic AGC
      who are undergoing palliative chemotherapy.

PMID- 24442665
TI  - Applications of titanium mesh tubing in external ear canal reconstruction in
      congenital aural atresia.
AB  - The aim of this study was to observe the effect of a titanium tube on external
      auditory canal reconstruction in congenital aural atresia and to assess the
      tube's effectiveness in preventing external canal stenosis or atresia after
      reconstruction. Reconstruction of the external ear canal with a titanium mesh
      tube was performed in 16 patients (16 ears) with congenital aural atresia at the
      First People's Hospital of Foshan. The titanium mesh tube was removed 1 year
      after surgery. The patients were followed up for 2 years (2 +/- 0.3 years), and
      all of the patients had formed a new external ear canal. There was no local
      infection, granulation tissue, re-stenosis, or atresia in any of the patients
      after surgery. All of the patients were content with their newly formed external
      ear canal. Titanium mesh tubing is safe and effective for reconstruction of the
      external ear canal during surgery for congenital aural atresia. 

PMID- 24442666
TI  - Metacarpal head resection for treatment of the fingers-in-palm deformity in
      longstanding neurological injury.

PMID- 24442667
TI  - Entrapment of the extensor indicis proprius tendon in the callus after a distal
      radial fracture.

PMID- 24442668
TI  - A4 Annular Flexor Pulley Injury in a Baseball Pitcher.

PMID- 24442669
TI  - Going "open" with mesoscopy: a new dimension on multi-view imaging.
AB  - OpenSPIM and OpenSpinMicroscopy emerged as open access platforms for Light Sheet
      and Optical Projection Imaging, often called as optical mesoscopy techniques.
      Both projects can be easily reproduced using comprehensive online instructions
      that should foster the implementation and further development of optical imaging
      techniques with sample rotation control. This additional dimension in an open
      system offers the possibility to make multi-view microscopy easily modified and
      will complement the emerging commercial solutions. Furthermore, it is deeply
      based on other open platforms such as MicroManager and Arduino, enabling
      development of tailored setups for very specific biological questions. In our
      perspective, the open access principle of OpenSPIM and OpenSpinMicroscopy is a
      game-changer, helping the concepts of light sheet and optical projection
      tomography (OPT) to enter the mainstream of biological imaging. 

PMID- 24442671
TI  - Sequence and phylogenetic analysis of H2N7 avian influenza viruses isolated from
      domestic ducks in Zhejiang Province, Eastern China, 2013.
AB  - Two H2N7 avian influenza viruses (AIVs) were isolated from domestic ducks in live
      poultry markets in Zhejiang Province, Eastern China, 2013. All viruses were
      characterized by whole-genome sequencing with subsequent phylogenetic analysis
      and genetic comparison. Phylogenetic analysis of all eight viral genes showed
      that the viruses clustered in the Eurasian lineage of AIVs and originated from
      genes reassortment among different viruses co-circulating in domestic ducks in
      Eastern China. The hemagglutinin cleavage site of all viruses indicated that the
      two strains were low-pathogenic avian influenza viruses. Considering the
      important role of the domestic ducks in the dissemination and reassortment of
      AIVs, continued surveillance of circulating H2 subtype AIVs in domestic ducks in
      live poultry markets is needed.

PMID- 24442670
TI  - Trauma and dissociation: implications for borderline personality disorder.
AB  - Psychological trauma can have devastating consequences on emotion regulatory
      capacities and lead to dissociative processes that provide subjective detachment
      from overwhelming emotional experience during and in the aftermath of trauma.
      Dissociation is a complex phenomenon that comprises a host of symptoms and
      factors, including depersonalization, derealization, time distortion,
      dissociative flashbacks, and alterations in the perception of the self.
      Dissociation occurs in up to two thirds of patients with borderline personality
      disorder (BPD). The neurobiology of traumatic dissociation has demonstrated a
      heterogeneity in posttraumatic stress symptoms that, over time, can result in
      different types of dysregulated emotional states. This review links the concepts
      of trauma and dissociation to BPD by illustrating different forms of emotional
      dysregulation and their clinical relevance to patients with BPD. 

PMID- 24442672
TI  - Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals
      position-dependent splicing modulation.
AB  - Splicing factor SRSF10 is known to function as a sequence-specific splicing
      activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify
      the extensive splicing network regulated by SRSF10 in chicken cells. We found
      that SRSF10 promoted both exon inclusion and exclusion. Motif analysis revealed
      that SRSF10 binding to cassette exons was associated with exon inclusion, whereas
      the binding of SRSF10 within downstream constitutive exons was associated with
      exon exclusion. This positional effect was further demonstrated by the
      mutagenesis of potential SRSF10 binding motifs in two minigene constructs.
      Functionally, many of SRSF10-verified alternative exons are linked to pathways of
      stress and apoptosis. Consistent with this observation, cells depleted of SRSF10
      expression were far more susceptible to endoplasmic reticulum stress-induced
      apoptosis than control cells. Importantly, reconstituted SRSF10 in knockout cells
      recovered wild-type splicing patterns and considerably rescued the stress-related
      defects. Together, our results provide mechanistic insight into SRSF10-regulated
      alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial
      role in cell survival under stress conditions. 

PMID- 24442673
TI  - A dynamic alternative splicing program regulates gene expression during terminal
      erythropoiesis.
AB  - Alternative pre-messenger RNA splicing remodels the human transcriptome in a
      spatiotemporal manner during normal development and differentiation. Here we
      explored the landscape of transcript diversity in the erythroid lineage by RNA
      seq analysis of five highly purified populations of morphologically distinct
      human erythroblasts, representing the last four cell divisions before
      enucleation. In this unique differentiation system, we found evidence of an
      extensive and dynamic alternative splicing program encompassing genes with many
      diverse functions. Alternative splicing was particularly enriched in genes
      controlling cell cycle, organelle organization, chromatin function and RNA
      processing. Many alternative exons exhibited differentiation-associated switches
      in splicing efficiency, mostly in late-stage polychromatophilic and
      orthochromatophilic erythroblasts, in concert with extensive cellular remodeling
      that precedes enucleation. A subset of alternative splicing switches introduces
      premature translation termination codons into selected transcripts in a
      differentiation stage-specific manner, supporting the hypothesis that alternative
      splicing-coupled nonsense-mediated decay contributes to regulation of erythroid
      expressed genes as a novel part of the overall differentiation program. We
      conclude that a highly dynamic alternative splicing program in terminally
      differentiating erythroblasts plays a major role in regulating gene expression to
      ensure synthesis of appropriate proteome at each stage as the cells remodel in
      preparation for production of mature red cells. 

PMID- 24442675
TI  - Isolation and characterization of cellulolytic bacteria from the Stain house
      Lake, Antarctica.
AB  - The main aim was to evaluate the occurrence of cellulolytic bacteria from the
      Stain house Lake, located at Admiralty Bay, Antarctica. Thick cotton string
      served as a cellulose bait for the isolation of bacteria. A total of 52 bacterial
      isolates were recovered and tested for their cellulase activity, and two of them,
      isolates CMAA 1184 and CMAA 1185, showed significant cellulolytic activity on
      carboxymethylcellulose agar plates. Phylogenetic analysis placed the isolates
      into the Bacillus 16S ribosomal RNA gene subclade. Both isolates produced a cold
      active cellulase which may play a crucial role in this extreme environment.

PMID- 24442674
TI  - Comparative ribosome profiling reveals extensive translational complexity in
      different Trypanosoma brucei life cycle stages.
AB  - While gene expression is a fundamental and tightly controlled cellular process
      that is regulated at multiple steps, the exact contribution of each step remains
      unknown in any organism. The absence of transcription initiation regulation for
      RNA polymerase II in the protozoan parasite Trypanosoma brucei greatly simplifies
      the task of elucidating the contribution of translation to global gene
      expression. Therefore, we have sequenced ribosome-protected mRNA fragments in T.
      brucei, permitting the genome-wide analysis of RNA translation and translational
      efficiency. We find that the latter varies greatly between life cycle stages of
      the parasite and ~100-fold between genes, thus contributing to gene expression to
      a similar extent as RNA stability. The ability to map ribosome positions at sub
      codon resolution revealed extensive translation from upstream open reading frames
      located within 5' UTRs and enabled the identification of hundreds of previously
      un-annotated putative coding sequences (CDSs). Evaluation of existing proteomics
      and genome-wide RNAi data confirmed the translation of previously un-annotated
      CDSs and suggested an important role for >200 of those CDSs in parasite survival,
      especially in the form that is infective to mammals. Overall our data show that
      translational control plays a prevalent and important role in different parasite
      life cycle stages of T. brucei. 

PMID- 24442676
TI  - Endoscopic resection of sporadic duodenal adenomas: comparison of endoscopic
      mucosal resection (EMR) with hybrid endoscopic submucosal dissection (ESD)
      techniques and the risks of late delayed bleeding.
AB  - BACKGROUND: Endoscopic resection (ER) of sporadic duodenal adenomas (SDAs) is an
      alternative treatment strategy to surgical excision but carries substantial risks
      of bleeding. Endoscopic submucosal dissection (ESD) of SDAs has a high rate of
      perforation. This study aimed to examine the outcome for ER of SDAs in two large
      UK centers, both using a novel hybrid endoscopic mucosal resection (EMR) with
      ESD. METHODS: Prospective endoscopy databases of ER cases were examined for the
      period January 2005 to December 2012. Records were analyzed for patient
      demographics, lesion size and morphology, staging investigations, procedural
      technique, outcomes, histology, complications, and follow-up assessments.
      RESULTS: The study included 34 patients. The mean adenoma size was 25 mm. Of the
      34 cases, 21 (62 %) were managed by the traditional snare EMR technique, 12 (35
      %) by the hybrid EMR-ESD technique, and 1 by full en bloc ESD. Successful
      resection was achieved in 33 (97 %) of the 34 cases. En bloc resection and
      recurrence rates did not differ significantly between the cases treated by EMR
      and those treated by hybrid EMR-ESD. Three episodes of significant delayed
      bleeding occurred 1-18 days after the procedure. No perforations or deaths
      occurred. The risk of delayed bleeding was higher for the lesions 30 mm in
      diameter or larger than for the lesions smaller than 30 mm (33% vs. 0 %; p =
      0.003). The risk of delayed bleeding was not related to the ER technique used
      (EMR, 9.5 %; ESD/hybrid, 7.7 %; p = 0.855). CONCLUSIONS: Endoscopic resection is
      an effective treatment for SDAs and can avoid the need for open surgery. This is
      the first series to report the use of a hybrid EMR-ESD technique for the
      treatment of SDAs in a Western setting. However, this technique did not confer
      any major outcome benefits over EMR. The risk of delayed bleeding is substantial,
      and bleeding may occur up to 18 days after the procedure. The risk of delayed
      bleeding was increased with lesions larger than 30 mm but was not influenced by
      the endoscopic technique.

PMID- 24442677
TI  - Annual case volume has no impact on patient outcomes in laparoscopic partial
      colectomy.
AB  - OBJECTIVES: Surgeon case volume has been utilized in the credentialing process as
      a surrogate for surgeon skill. The purpose of this study was to compare objective
      outcome measures of laparoscopic partial colectomies performed by
      laparoscopically skilled surgeons with varying annual case census. METHODS: We
      performed a retrospective cohort review of all patients (n = 255) undergoing
      elective laparoscopic partial colectomy. Patients were grouped according to
      surgeon's annual case volume as low annual case volume (LV; n = 48) and high
      annual case volume (HV; n = 207). HV is defined as performing >20 total cases and
      >25 cases per year. All demographic and clinical variables were evaluated with
      univariate logistic regression followed by a multivariate logistic regression
      model for variables approaching significance. RESULTS: Demographic variables were
      found to be similar between groups. Only median estimated blood loss (100 vs. 150
      mL for HV; p = 0.040) was found to be significantly different between groups.
      However, this was clinically insignificant, as it did not lead to an increased
      rate of blood transfusions (0.0 vs. 3.9 % for HV surgeons; p = 0.184). All other
      variables were similar in both univariate and multivariate logistic regression
      models. CONCLUSIONS: Among surgeons with advanced laparoscopic training, the data
      suggest that LV surgeons are able to achieve similar outcomes as those who
      perform the operation routinely. Annual case volume should not be given undue
      emphasis when deciding whether to award privileges for laparoscopic partial
      colectomy.

PMID- 24442678
TI  - Simulation-based training for thoracoscopic lobectomy: a randomized controlled
      trial: virtual-reality versus black-box simulation.
AB  - BACKGROUND: Video-assisted thoracic surgery is gradually replacing conventional
      open thoracotomy as the method of choice for the treatment of early-stage non
      small cell lung cancers, and thoracic surgical trainees must learn and master
      this technique. Simulation-based training could help trainees overcome the first
      part of the learning curve, but no virtual-reality simulators for thoracoscopy
      are commercially available. This study aimed to investigate whether training on a
      laparoscopic simulator enables trainees to perform a thoracoscopic lobectomy.
      METHODS: Twenty-eight surgical residents were randomized to either virtual
      reality training on a nephrectomy module or traditional black-box simulator
      training. After a retention period they performed a thoracoscopic lobectomy on a
      porcine model and their performance was scored using a previously validated
      assessment tool. RESULTS: The groups did not differ in age or gender. All
      participants were able to complete the lobectomy. The performance of the black
      box group was significantly faster during the test scenario than the virtual
      reality group: 26.6 min (SD 6.7 min) versus 32.7 min (SD 7.5 min). No difference
      existed between the two groups when comparing bleeding and anatomical and non
      anatomical errors. CONCLUSION: Simulation-based training and targeted
      instructions enabled the trainees to perform a simulated thoracoscopic lobectomy.
      Traditional black-box training was more effective than virtual-reality
      laparoscopy training. Thus, a dedicated simulator for thoracoscopy should be
      available before establishing systematic virtual-reality training programs for
      trainees in thoracic surgery.

PMID- 24442679
TI  - Distribution of innate ability for surgery amongst medical students assessed by
      an advanced virtual reality surgical simulator.
AB  - BACKGROUND: Surgery is a craft profession requiring individuals with specific,
      well-documented innate aptitude for manipulative skills. Yet in most countries,
      the current selection process of surgical trainees does not include aptitude
      testing for the psychomotor and manipulative skills of candidates. METHODS: A
      total of 125 participants (121 medical students and four expert surgeons)
      performed all 26 exercises of the da Vinci Skills Simulator, with six exercises
      being identified as metrics of aptitude for manipulative and psychomotor skills.
      The expert surgeons were enrolled as the control group to validate the
      performance of the most talented students. RESULTS: Eight students (6.6%)
      significantly outperformed the remaining 113, obtaining a median value of the sum
      of weighted overall score on the six selected exercises of 52.7% versus 21.0% (p
      < 0.001). In contrast, 14 students (11.6%) performed significantly worse and well
      below the performance of the other 107, with a median value of overall score of
      8.7% versus 24.1 (p < 0.001). There was no statistically significant difference
      between expert surgeons (control group) and the eight talented students (62.1%
      vs. 52.7%, respectively; p = 0.368). No significant correlation between exposure
      to video games and overall score (rho = 0.330) was observed. CONCLUSIONS: In
      terms of innate aptitude for manipulative and psychomotor abilities, the present
      investigation has documented two subpopulations that fall outside the norm for
      the group of medical students recruited for the study: (i) a small group (6.6%)
      with a high level and (ii) a larger cohort (11.6%) with low level (significantly
      below the norm) innate aptitude for surgery. Exposure to video game experience
      did not appear to influence performances on the da Vinci Skills Simulator.

PMID- 24442680
TI  - Complete defect closure of gastric submucosal tumors with purse-string sutures.
AB  - BACKGROUND: Gastric submucosal tumors (SMTs) originating from the muscularis
      propria layer are treated endoscopically. Successful closure of the wall defect
      is a critical step. This study evaluated the safety and feasibility of the
      endoscopic purse-string suture (EPSS) method using an endoloop and several
      metallic clips after endoscopic full-thickness resection (EFTR) or perforation
      due to endoscopic submucosal dissection (ESD). METHODS: From December 2009 to
      April 2013, 30 patients with SMTs originating from the muscularis propria layer
      who received EFTR or ESD were retrospectively analyzed. After successful tumor
      resection, an endoloop was anchored onto the circumferential margin of the
      gastric defect with several metallic clips and tightened gently. Patient
      characteristics, tumor size, en bloc resection, and postoperative complications
      were evaluated. RESULTS: For all 30 patients, EPSS was successfully performed
      after EFTR or perforation due to ESD. The mean diameter of the resected specimen
      was 1.9 cm. No severe complications occurred during or after the procedure. The
      lesions were healed 1 month after the procedure, as confirmed endoscopically.
      CONCLUSION: The EPSS method using an endoloop and clips is an effective and safe
      technique for closing the gastric defect after EFTR or perforation due to ESD.

PMID- 24442681
TI  - Remodeling characteristics and collagen distribution in synthetic mesh materials
      explanted from human subjects after abdominal wall reconstruction: an analysis of
      remodeling characteristics by patient risk factors and surgical site
      classifications.
AB  - BACKGROUND: The purpose of this study was to evaluate the associations between
      patient characteristics or surgical site classifications and the histologic
      remodeling scores of synthetic meshes biopsied from their abdominal wall repair
      sites in the first attempt to generate a multivariable risk prediction model of
      non-constructive remodeling. METHODS: Biopsies of the synthetic meshes were
      obtained from the abdominal wall repair sites of 51 patients during a subsequent
      abdominal re-exploration. Biopsies were stained with hematoxylin and eosin, and
      evaluated according to a semi-quantitative scoring system for remodeling
      characteristics (cell infiltration, cell types, extracellular matrix deposition,
      inflammation, fibrous encapsulation, and neovascularization) and a mean composite
      score (CR). Biopsies were also stained with Sirius Red and Fast Green, and
      analyzed to determine the collagen I:III ratio. Based on univariate analyses
      between subject clinical characteristics or surgical site classification and the
      histologic remodeling scores, cohort variables were selected for multivariable
      regression models using a threshold p value of <=0.200. RESULTS: The model
      selection process for the extracellular matrix score yielded two variables:
      subject age at time of mesh implantation, and mesh classification (c-statistic =
      0.842). For CR score, the model selection process yielded two variables: subject
      age at time of mesh implantation and mesh classification (r (2) = 0.464). The
      model selection process for the collagen III area yielded a model with two
      variables: subject body mass index at time of mesh explantation and pack-year
      history (r (2) = 0.244). CONCLUSION: Host characteristics and surgical site
      assessments may predict degree of remodeling for synthetic meshes used to
      reinforce abdominal wall repair sites. These preliminary results constitute the
      first steps in generating a risk prediction model that predicts the patients and
      clinical circumstances for which non-constructive remodeling of an abdominal wall
      repair site with synthetic mesh reinforcement is most likely to occur.

PMID- 24442682
TI  - CO(2) pneumoperitoneum increases secretory IgA levels in the gut compared with
      laparotomy in an experimental animal model.
AB  - BACKGROUND: Secretory immunoglobulin A (s-IgA) plays an important role in both
      gut and systemic immunity. This study aimed to investigate the production of s
      IgA resulting from a CO2 pneumoperitoneum compared with a laparotomy. METHODS:
      Using enzyme-linked immunosorbent assays, s-IgA in stool, malondialdehyde (MDA),
      and Toll-like receptor 4 (TLR4) in the ileal tissue were evaluated as markers for
      gut and systemic immune responses in an animal model. The rats were randomly
      divided into (i) anesthesia-only as the control group; (ii) laparotomy-only as
      the open group; and (iii) CO2 pneumoperitoneum-only as the pneumoperitoneum
      group. To evaluate the gut immune system in a time-dependent manner, each group
      was further divided into short- and long-time subgroups. RESULTS: s-IgA levels
      did not increase in the open group but significantly increased in the
      pneumoperitoneum group compared with the control group (p < 0.05). In addition, s
      IgA levels in the long-time subgroup significantly increased compared with the
      short-time subgroup of the pneumoperitoneum group (p < 0.05). TLR4 levels steeply
      and gradually increased in the open and pneumoperitoneum groups, respectively.
      MDA levels in the pneumoperitoneum group increased during the early phase and
      were significantly higher than those in the open group at 24 h (p < 0.05).
      CONCLUSIONS: This study demonstrated that s-IgA levels in stool increased in the
      pneumoperitoneum group compared with the open group, suggesting that CO2
      pneumoperitoneum may cause transitory damage to the intestinal mucosa.

PMID- 24442684
TI  - Reusable single-port access device shortens operative time and reduces operative
      costs.
AB  - BACKGROUND: In recent years, single-port laparoscopy (SPL) has become an
      attractive approach for performing surgical procedures. The pitfalls of this
      approach are technical and financial. Financial concerns are due to the increased
      cost of dedicated devices and prolonged operating room time. Our aim was to
      calculate the cost of SPL using a reusable port and instruments in order to
      evaluate the cost difference between this approach to SPL using the available
      disposable ports and standard laparoscopy. METHODS: We performed 22 laparoscopic
      procedures via the SPL approach using a reusable single-port access system and
      reusable laparoscopic instruments. These included 17 cholecystectomies and five
      other procedures. Operative time, postoperative length of stay (LOS) and
      complications were prospectively recorded and were compared with similar data
      from our SPL database. Student's t test was used for statistical analysis.
      RESULTS: SPL was successfully performed in all cases. Mean operative time for
      cholecystectomy was 72 min (range 40-116). Postoperative LOS was not changed from
      our standard protocols and was 1.1 days for cholecystectomy. The postoperative
      course was within normal limits for all patients and perioperative morbidity was
      recorded. Both operative time and length of hospital stay were shorter for the 17
      patients who underwent cholecystectomy using a reusable port than for the matched
      previous 17 SPL cholecystectomies we performed (p < 0.001). Prices of disposable
      SPL instruments and multiport access devices as well as extraction bags from
      different manufacturers were used to calculate the cost difference. Operating
      with a reusable port ended up with an average cost savings of US$388 compared
      with using disposable ports, and US$240 compared with standard laparoscopy.
      CONCLUSION: Single-port laparoscopic surgery is a technically challenging and
      expensive surgical approach. Financial concerns among others have been advocated
      against this approach; however, we demonstrate herein that using a reusable port
      and instruments reduces operative time and overall operative costs, even beyond
      the cost of standard laparoscopy.

PMID- 24442686
TI  - Processes to separate enantiomers.
AB  - The provision of pure enantiomers is of increasing importance not only for the
      pharmaceutical industry but also for agrochemistry and biotechnology. In general,
      there are two rival approaches to provide pure enantiomers. The "chiral" approach
      is based on developing an asymmetric synthesis of just one of the enantiomers,
      while the "racemic" approach is based on separating mixtures of the two
      enantiomers. In the last few years remarkable progress has been achieved in the
      latter area. This Review focuses in particular on enantioselective
      crystallization processes and preparative chromatography, including hybrid
      processes and the incorporation of racemization steps. Several examples from our
      research are used for illustration purposes. 

PMID- 24442683
TI  - A prospective audit of the use of diagnostic laparoscopy to establish the
      diagnosis of abdominal tuberculosis.
AB  - BACKGROUND: The incidence of abdominal tuberculosis is much higher in an HIV
      positive cohort. The use of laparoscopy in the diagnostic work-up of suspected
      abdominal tuberculosis is underutilized and its use and efficacy in the context
      of HIV co-infection has never been examined. METHODS: A prospective clinical
      audit of the use of diagnostic laparoscopy was conducted in patients with
      clinically suspected abdominal tuberculosis but histologically or
      microbiologically unconfirmed tuberculosis at any site. RESULTS: From January
      2008 to June 2010, 81 patients underwent diagnostic laparoscopy; 34 were male and
      47 were female, with a mean age of 33 years, and 77 % were HIV-positive. Fifty
      five patients (68 %) had positive histology or culture for tuberculosis. In 15
      patients (19 %), histology revealed non-specific inflammation, no pathology was
      found in one patient, and no specimen was taken from one patient. Eighty percent
      of peritoneal deposits and 77 % of lymph nodes were positive for tuberculosis,
      whereas 35 % of ascitic fluid cultures were positive. In nine patients (11 %) an
      alternative diagnosis was found; nine patients (11 %) had conversion to
      laparotomy. There was no procedure-related death. Nine patients (11 %) died
      during the 2-month follow-up period. CONCLUSIONS: Diagnostic laparoscopy avoids
      the morbidity and mortality of laparotomy in chronically ill patients, and
      reduces the rate of misdiagnosis of other abdominal conditions and unnecessary
      long-term therapy. Diagnostic laparoscopy and tissue sampling is a viable and
      reliable strategy in patients with suspected abdominal tuberculosis.

PMID- 24442688
TI  - Education of psychiatry residents in ethics.

PMID- 24442689
TI  - Ethics in academic psychiatry.

PMID- 24442685
TI  - Construct validity of individual and summary performance metrics associated with
      a computer-based laparoscopic simulator.
AB  - BACKGROUND: Computer-based surgical simulators capture a multitude of metrics
      based on different aspects of performance, such as speed, accuracy, and movement
      efficiency. However, without rigorous assessment, it may be unclear whether all,
      some, or none of these metrics actually reflect technical skill, which can
      compromise educational efforts on these simulators. We assessed the construct
      validity of individual performance metrics on the LapVR simulator (Immersion
      Medical, San Jose, CA, USA) and used these data to create task-specific summary
      metrics. METHODS: Medical students with no prior laparoscopic experience
      (novices, N = 12), junior surgical residents with some laparoscopic experience
      (intermediates, N = 12), and experienced surgeons (experts, N = 11) all completed
      three repetitions of four LapVR simulator tasks. The tasks included three basic
      skills (peg transfer, cutting, clipping) and one procedural skill (adhesiolysis).
      RESULTS: We selected 36 individual metrics on the four tasks that assessed six
      different aspects of performance, including speed, motion path length, respect
      for tissue, accuracy, task-specific errors, and successful task completion. Four
      of seven individual metrics assessed for peg transfer, six of ten metrics for
      cutting, four of nine metrics for clipping, and three of ten metrics for
      adhesiolysis discriminated between experience levels. Time and motion path length
      were significant on all four tasks. We used the validated individual metrics to
      create summary equations for each task, which successfully distinguished between
      the different experience levels. CONCLUSION: Educators should maintain some
      skepticism when reviewing the plethora of metrics captured by computer-based
      simulators, as some but not all are valid. We showed the construct validity of a
      limited number of individual metrics and developed summary metrics for the LapVR.
      The summary metrics provide a succinct way of assessing skill with a single
      metric for each task, but require further validation.

PMID- 24442687
TI  - Patterns of nodal staging during breast conservation surgery in the medicare
      patient: will the ACOSOG Z0011 trial change the pattern of care?
AB  - ACOSOG Z0011 spares axillary dissection (AD) in breast conservation surgery (BCS)
      patients with T1/T2 tumors and 1-2 positive nodes. Current patterns of care and
      the impact of Z0011 on AD versus additional surgery rates for Medicare patients
      undergoing BCS are unknown. SEER data linked to Medicare claims for 1999-2005
      were reviewed for women with invasive nonmetastatic breast cancer who underwent
      nodal staging on the same day as BCS. There were 3,280 women with T1/T2 tumors
      and positive nodes who underwent same-day nodal staging; 2,532 (77.2 %) of these
      women had 1-2 positive nodes. Assuming 25.7 % have extracapsular extension, 651
      women would require AD. However, 1,881 women, or 57.4 % of those with T1/T2
      tumors and positive nodes, would be spared AD. Meanwhile, among the 748 women
      having >= 3 positive nodes, 579 underwent same-day AD, but under Z0011, would now
      wait for permanent section. A total of 160 of these women underwent re-excision
      or completion mastectomy at a later date anyway, when delayed AD could be
      performed. The remaining 419 women with >= 3 positive nodes would require an
      additional surgery date for the sole purpose of completion AD. The Z0011 paradigm
      would consequently necessitate an additional surgery date for 1,070 (651 + 419)
      women, or 32.6 % of those with T1/T2 tumors and positive nodes. The Z0011
      paradigm appears to increase the number of Medicare patients undergoing BCS who
      require an additional surgery date but decrease the number requiring AD to a
      greater extent. Future changes in the use of AD or axillary irradiation may yet
      modify that impact substantially.

PMID- 24442690
TI  - What and how psychiatry residents at ten training programs wish to learn about
      ethics.
AB  - The study's objective was to survey what and how psychiatry residents want to
      learn about ethics during residency. A 4-page questionnaire developed for this
      study was sent to 305 residents at 10 adult psychiatry programs in the United
      States. One-hundred and eighty-one (59%) of those surveyed responded. Seventy-six
      percent reported facing an ethical dilemma in residency for which they felt
      unprepared. Forty-six percent reported having received no ethics training during
      residency. More than 50% of the respondents requested that "more" curricular
      attention be paid to 19 specific ethics topics and more than 40% for 25 topics.
      Preferences with respect to learning methods are presented. This survey may
      provide guidance in structuring the content and process of ethics education for
      psychiatry residents. These findings should stimulate the efforts of faculty to
      commit time and attention to this important curricular area. 

PMID- 24442691
TI  - Teaching ethics in psychiatry : a problem-based learning approach.
AB  - During the last two decades, the teaching of ethics in the field of medicine,
      particularly in psychiatry, has become the subject of increased attention. For
      this type of training to be effective, it should be practical (as opposed to
      theoretical), focused on the decision-making process (as opposed to the rote
      learning of concepts), and, eventually, self-directed. This article suggests that
      a problem-based learning approach is an ideal method for reaching these goals. A
      case illustration is presented to underscore the effectiveness of the method, as
      well as a rationale for its use. This article will assist psychiatric educators
      in becoming familiar with this approach and will encourage them to use this
      method in their training programs. 

PMID- 24442692
TI  - Ethics and child and adolescent psychiatry : curricular design and clinical
      teaching.
AB  - This article describes the development and experience of one child and adolescent
      psychiatry training program's approach to the creation and content of an ethics
      curriculum. Currently, a series of lecture-discussions covering ethics and
      forensic subjects are presented during the first year. Ethical principles,
      models, and reasoning are introduced, and their knowledge is deemed important to
      arrive at sensible resolutions of clinical dilemmas. Simultaneously, an emphasis
      on discussion of ethical dimensions of cases is expected during conferences,
      clinical experiences, and supervision throughout the 2 years of training. This
      article presents an analysis of one case for illustration. In addition, questions
      educators should consider prior to curriculum construction, related to the goals
      of instruction in ethics, are reviewed. 

PMID- 24442693
TI  - Exploring the ethics of cost containment in psychiatric training.
AB  - With the introduction of managed health care, the medical field finds itself in
      what seems to be an ethically compromised position. Changes in society have
      created a new role for the physician: that of manager of health care resources.
      Ethical principles have not evolved quickly enough to keep pace with these
      changes. Psychiatry faces unique problems because mental health care costs have
      been singled out for reduction by health care purchasers. Despite this present
      state of turmoil and transition, the profession needs to provide its students
      with the necessary training to practice ethical psychiatry. The author suggests
      teaching strategies and exercises to assist faculty wishing to include the ethics
      of cost containment in their curriculum. 

PMID- 24442694
TI  - Fifteen years of teaching psychiatric law and ethics to residents.
AB  - In 1978, the authors, a psychiatrist and a lawyer, began a course in law and
      ethics for postgraduate year A psychiatry residents that continues today. The
      authors review the course in terms of its evolution, effect on residents and
      faculty during the course, evaluation by residents immediately after the course
      and since graduation, and future prospects of such a course being started at
      other institutions. 

PMID- 24442695
TI  - Clinical ethics teaching in psychiatric supervision.
AB  - Supervision of psychiatric residents provides a natural context for clinical
      ethics teaching. In this article, the authors discuss the need for ethics
      education in psychiatry residencies and describe how the special attributes of
      supervision allow for optimal ethics training for psychiatry residents in their
      everyday encounters with ethical problems. Ethical decision making in clinical
      settings is briefly reviewed, and a 6-step strategy for clinical ethics training
      in psychiatric supervision is outlined. The value of the clinical ethics
      supervisory strategy for teaching and patient care is illustrated through four
      case examples. 

PMID- 24442696
TI  - Upper airway imaging in sleep-disordered breathing.
AB  - Our understanding of sleep-disordered breathing has evolved considerably over the
      past three decades, and clinical techniques of evaluation have progressed
      tremendously. Myriad imaging techniques are now available for the physician to
      approach the dynamic features resulting in turbulent airflow, upper airway
      narrowing or collapse at different levels. Controversy exists in the choice of
      investigations, probably because the best evaluation should be a combination of
      different techniques. Physical, radiographic, endoscopic and acoustic evaluations
      could be integrated to understand the degree and the levels of airway reduction
      and/or obstruction in a given patient. This review focuses on cost-effective and
      easily implemented techniques in daily practice, allowing quality assessment of
      the dynamic anatomy of sleep-disordered breathing: cephalometry, (sleep
      )endoscopy and acoustic reflectometry of the upper airway.

PMID- 24442697
TI  - Plant protoplast fusion and growth of intergeneric hybrid cells.
AB  - Interspecific and intergeneric fusions of plant protoplasts were induced by
      polyethylene glycol (PEG) 1540 or 4000. The frequency of heterokaryocyte
      formation (or rate of fusion) was much higher when PEG was eluted with a high pH
      high Ca(2+) solution or a salt solution than when it was eluted with a protoplast
      culture medium. The frequency of heterokaryocyte formation was also affected by
      the types of enzymes used for wall degradation, duration of enzyme incubation and
      molality of the PEG solutions.The maximum frequency of heterokaryocyte formation
      was 23% for V. hajastana Grossh.-soybean (Glycine max L.) and barley (Hordeum
      vulgare L.)-soybean, 35% for pea (Pisum sativum L.)-soybean, 20% for pea-V.
      hajastana, 14% for corn (Zea mays L.)-soybean and 10% for V. villosa Roth-V.
      hajastana.40% of the barley-soybean, corn-soybean and pea-soybean
      heterokaryocytes divided at least once. Some divided many times and formed
      clusters of up to 100 cells in 2 weeks. The heterokaryocytes of soybean-V.
      hajastana, V. villosa-V. hajastana also divided. Of the PEG-treated protoplasts
      of N. langsdorffii and N. glauca 13.5% developed into tumor-like calli. The
      morphology of these calli was very much like that of the tumors produced on
      amphidiploid plants of N. langsdorffii x glauca.Nuclear staining indicated that
      heterokaryocytes of V. hajastana-soybean, pea-soybean, corn-soybean and barley
      soybean could undergo mitosis. Nuclear divisions in a heterokaryocyte were
      usually synchronized or almost synchronized. Nuclear fusion and true hybrid
      formation usually occurred during the first mitotic division after protoplast
      fusion. A hybrid of barley-soybean in third cell division was observed. The
      frequency of heterokaryocytes which underwent nuclear fusion has not been
      determined. Multipole formation and chimeral cell colonies were also observed. 

PMID- 24442698
TI  - Phloem bleeding from legume fruits-A technique for study of fruit nutrition.
AB  - Bleeding from phloem of cut distal tips of attached fruits was demonstrated in
      the genera Spartium, Genista, Lupinus and Jacksonia. Bleeding occurred over a 2
      25 min period enabling 0.5-10 MUl of sap to be collected from a fruit. A detailed
      study of Lupinus albus L. showed that exudation rate declined exponentially after
      cutting, but without any change with time in solute levels in exudate. Bleeding
      resumed at its initial rate and solute concentration on recutting the fruit
      tip.Phloem exudates had a high pH (7.8-8.0), a sucrose content of 100-210 mg ml(
      1) but only traces of monosaccharides. Surrounding pod tissues contained only 15
      35 mg ml(-1) of sugars (tissue water basis) more than two thirds of this
      monosaccharide. Amino compounds were present in phloem exudates at 8-28 mg ml(
      1), asparagine and glutamine predominating but a wide spectrum of other amino
      acids being also present. No significant differences in levels of organic solutes
      were observed in phloem exudates collected from tips of attached versus detached
      fruits, from phloem exudates collected from fruit tips versus pedicels, or from
      basal versus distal ends of a detached fruit.Potassium was the major cation (1.5
      2.2 mg ml(-1)) of the phloem exudate, Ca(2+) was at a much lower level than
      either Mg(2+) or Na(+). Trace element levels in phloem exudates appeared to be
      influenced by availability to the plant from the rooting medium. Nitrate was
      absent though detectable in non-vascular tissues of the shoot. (14)C- labelled
      assimilates were detected in exudates of L. albus one hour after feeding a source
      leaf (14)CO2; sucrose, organic acids and certain amino compounds achieved high
      specific labelling. (14)CO2 feeding studies coupled with the phloem bleeding
      technique revealed highly specific source-sink relationships between foliar
      organs and fruits of the primary inflorescence. 

PMID- 24442699
TI  - Changes in specific radioactivity of sunflower leaf metabolites during
      photosynthesis in (14)CO 2 and (12)CO 2 at three concentrations of CO 2.
AB  - Sunflower (Helianthus annuus L.) leaf discs were exposed to (14)CO2 or (14)CO2
      followed by (12)CO2 at 21% O2 and three different CO2 concentrations. After
      intervals of up to 15 min, the specific activity of some photosynthetic
      intermediates was determined. At all CO2 concentrations, the specific activity of
      3-phosphoglyceric acid (3-PGA) increased most rapidly and after 15 min of (14)CO2
      feeding was 92% (967 ppm CO2), 87% (400 ppm CO2) and 53% (115 ppm CO2) of CO2
      supplied to the assimilation chamber. The specific activity of glycine, serine
      and the photorespiratory CO2 was similar at all CO2 concentrations, in aggreement
      with their proposed close metabolic relationship in the glycolate pathway.
      However, the kinetics of serine and glycine labelling suggested that serine was
      not totally derived from glycine. Because the specific activity of these
      glycolate-pathway intermediates was very differnet from that of 3-PGA at all CO2
      concentrations, not all of the carbon traversing this pathway came directly from
      the Calvin cycle. The non-equilibration of the 3-PGA with the feeding gas
      reflects the recycling of C from the glycolate pathway into the photosynthetic
      reduction cycle. Measurements of the rates of CO2 evolution in the light and
      estimates of the C flux through the glycolate pathway suggest that the
      photorespiratory activity was high and similar at 115 ppm CO2 and 400 ppm CO2 but
      inhibited at 967 ppm CO2. 

PMID- 24442700
TI  - All-trans-farnesol: a naturally occurring antitranspirant?
AB  - Lipid extracts from Sorghum sudanese Stapf (cv Piper) that had been subjected to
      different degrees of water stress contained increasing amounts of a
      sesquiterpenoid, other than abscisic acid, as the amount of stress increased and
      subsequent bioassay showed that this substance was capable of inducing stomatal
      closure. Infra-red, nuclear magnetic resonance and mass spectral analysis after
      final purification by preparative gas-liquid chromatography showed conclusively
      that this substance was identical to all-trans-farnesol. Various derivatives,
      homologues and isoprenologues of all-trans-farnesol were tested for their ability
      to close stomata. Only trans-nerolidol approached all-trans-farnesol in activity
      when applied to isolated epidermis of Commelina communis L. Stomatal closure was
      induced slightly faster and more completely in the presence of all-trans-farnesol
      than in the presence of ABA at a similar molar concentration. 

PMID- 24442701
TI  - Inverse dark reversion of phytochrome: An explanation.
AB  - Pea epicotyl tissue freeze dried with phytochrome (P) in the red absorbing (Pr)
      form, on exposure to red light does not form the far-red absorbing form of P
      (Pfr), but forms the intermediate P698 which reverts to Pr in darkness. Similar
      tissue containing the pigment as Pfr undergoes a photoreversible reaction on
      exposure to alternate red and far-red light. This represents the
      photoreversibility between Pfr and the intermediate P650. The difference spectrum
      of this reaction is similar to that of phytochrome photoconversion in dry
      cucumber seeds. P650 is shown to revert slowly to Pfr in darkness and it is
      proposed that this reaction accounts for the observation of apparent inverse dark
      reversion in cucumber seeds. Partial rehydration of freeze-dried tissue
      containing Pr, by means of 80% glycerol: 20% water (v/v), partially restores
      photoreversibility between Pr and Pfr. In such samples Pfr formation from
      intermediates, however, is slow and continues for several min in the dark after
      exposure to red light. This reaction can simulate the apparent inverse dark
      reversion observed in many seeds during early stages of imbibition. In this case
      Pfr appears from an intermediate produced by exposure to red light, which has not
      had time to form Pfr during the normal assay period. These two processes of Pfr
      production from intermediates in darkness, present under conditionsof partial or
      extreme dehydration, can explain previous experimental observations interpreted
      as inverse dark reversion.It is therefore proposed that the process, formerly
      described as 'inverse dark reversion', is not a transformation of Pr to Pfr and
      that there is not a separate form of phytochrome responsible for this reaction. 

PMID- 24442702
TI  - Waxy structures in the lenticels of potato tubers and their possible effects on
      gas exchange.
AB  - The presence of waxy outgrowths on the surface of certain cells in potato
      lenticels is described. The role of wax in gas exchange through the lenticels is
      discussed. 

PMID- 24442703
TI  - The role of proline accumulation in halophytes.
AB  - It is shown that in the majority of higher plant halophytes examined proline is
      the major component of the amino acid pool in plants collected from the field. In
      Triglochin maritima L. free proline can represent 10-20% of the shoot dry weight.
      Under non-saline conditions proline levels are low and increase as the salinity
      is raised. Comparisons of inland and coastal populations of Ameria maritima
      Willd. suggest that the capacity to accumulate proline is correlated with salt
      tolerance. It is suggested that proline functions as a source of solute for
      intracellular osmotic adjustments under saline conditions. 

PMID- 24442704
TI  - [Promoting effect of blue light on the production of carotenoids in a yellow
      chlorella mutant].
AB  - In growing as well as in resting cells of a chlorophyll-free yellow mutant of
      Chlorella vulgaris (211-11h/20) synthesis of carotenoids is enhanced by blue
      light. Permanent irradiation is necessary to maintain the effect (Fig. 2). At
      wavelengths around 454 nm the additional carotenoid production is half-saturated
      at about 1000 erg cm(-2)s(-1) and saturated at about 4000 erg cm(-2)s(-1) (Fig.
      3). An action spectrum exhibits highest efficiency of wavelengths around 465 and
      370 nm, a minimum near 400 nm and inefficacy of yellow, red and far-red light
      (Fig. 4). This wavelength dependence resembles those of light enhanced O2-uptake,
      carbohydrate consumption and gain of organically bound nitrogen by the organism. 

PMID- 24442705
TI  - [Transport and metabolism of 2-[(14)C]abscisic acid in root segments of Phaseolus
      coccineus L].
AB  - Movement of 2-[(14)C]ABA through 1.5 cm and 5 cm long root segments of P.
      coccineus L. was acropetally polarised. The velocity of acropetal transport of
      [(14)C]ABA in 1.5 cm long segments was 4-5 mm.h(-1). Up to 11 h after the start
      of incubation [(14)C]ABA could be extracted unchanged. Beyond this time
      radioactivity became associated to an unidentified compound, which shows
      chromatographic qualities similar to those of Milborrow's "Metabolite C"
      (Biochemistry & Physiol. Plant Growth Substances, 1531, Runge Press Ottawa, 1968;
      and Chem. Comm. 966, 1969). 

PMID- 24442706
TI  - The biosynthesis of a C19-gibberellin from mevalonic acid in a cell-free system
      from a higher plant.
AB  - Incubation of a cell-free system from immature seeds of Cucurbita maxima Duch.
      with [(14)C]GA12-aldehyde derived from [(14)C]mevalonic acid in the same system
      yielded the C19-gibberellin, [(14)C]GA4, in addition to the C20-gibberellins,
      [(14)C]GA37, [(14)C]GA13 and [(14)C]GA43. (GA-gibberellin). 

PMID- 24442707
TI  - Heavy meromyosin complexing filaments in the phloem of Vicia faba and Xylosma
      congestum.
AB  - Stem sections of Vicia faba L. were incubated with rabbit-muscle heavy meromyosin
      (HMM) and HMM complexes with phloem filaments (P-protein) were observed with the
      electron microscope. Treatment of sections of Vicia faba and of Xylosma congestum
      (Lour.) Merr. with fluorescent HMM resulted in a weak fluorescence of the phloem
      region. Inasmuch as HMM-binding is believed to be specific for actin-like
      proteins, it is proposed to classify P-protein as such. 

PMID- 24442708
TI  - The phenotypic spectrum of DYT24 due to ANO3 mutations.
AB  - Genes causing primary dystonia are rare. Recently, pathogenic mutations in the
      anoctamin 3 gene (ANO3) have been identified to cause autosomal dominant
      craniocervical dystonia and have been assigned to the dystonia locus dystonia-24
      (DYT24). Here, we expand on the phenotypic spectrum of DYT24 and provide
      demonstrative videos. Moreover, tremor recordings were performed, and back
      averaged electroencephalography, sensory evoked potentials, and C-reflex studies
      were carried out in two individuals who carried two different mutations in ANO3.
      Ten patients from three families are described. The age at onset ranged from
      early childhood to the forties. Cervical dystonia was the most common site of
      onset followed by laryngeal dystonia. The characteristic feature in all affected
      individuals was the presence of tremor, which contrasts DYT24 from the typical
      DYT6 phenotype. Tremor was the sole initial manifestation in some individuals
      with ANO3 mutations, leading to misdiagnosis as essential tremor.
      Electrophysiology in two patients with two different mutations showed co
      contraction of antagonist muscles, confirming dystonia, and a 6-Hz arm tremor at
      rest, which increased in amplitude during action. In one of the studied patients,
      clinically superimposed myoclonus was observed. The duration of the myoclonus was
      in the range of 250 msec at about 3 Hz, which is more consistent with subcortical
      myoclonus. In summary, ANO3 causes a varied phenotype of young-onset or adult
      onset craniocervical dystonia with tremor and/or myoclonic jerks. Patients with
      familial cervical dystonia who also have myoclonus-dystonia as well as patients
      with prominent tremor and mild dystonia should be tested for ANO3 mutations.

PMID- 24442709
TI  - Helicobacter pylori RNA polymerase alpha-subunit C-terminal domain shows features
      unique to E-proteobacteria and binds NikR/DNA complexes.
AB  - Bacterial RNA polymerase is a large, multi-subunit enzyme responsible for
      transcription of genomic information. The C-terminal domain of the alpha subunit
      of RNA polymerase (alphaCTD) functions as a DNA and protein recognition element
      localizing the polymerase on certain promoter sequences and is essential in all
      bacteria. Although alphaCTD is part of RNA polymerase, it is thought to have once
      been a separate transcription factor, and its primary role is the recruitment of
      RNA polymerase to various promoters. Despite the conservation of the subunits of
      RNA polymerase among bacteria, the mechanisms of regulation of transcription vary
      significantly. We have determined the tertiary structure of Helicobacter pylori
      alphaCTD. It is larger than other structurally determined alphaCTDs due to an
      extra, highly amphipathic helix near the C-terminal end. Residues within this
      helix are highly conserved among E-proteobacteria. The surface of the domain that
      binds A/T rich DNA sequences is conserved and showed binding to DNA similar to
      alphaCTDs of other bacteria. Using several NikR dependent promoter sequences, we
      observed cooperative binding of H. pylori alphaCTD to NikR:DNA complexes. We also
      produced alphaCTD lacking the 19 C-terminal residues, which showed greatly
      decreased stability, but maintained the core domain structure and binding
      affinity to NikR:DNA at low temperatures. The modeling of H. pylori alphaCTD into
      the context of transcriptional complexes suggests that the additional amphipathic
      helix mediates interactions with transcriptional regulators. 

PMID- 24442710
TI  - Cloning, expression, and characterization of thermophilic L-asparaginase from
      Thermococcus kodakarensis KOD1.
AB  - The present study demonstrates cloning, expression, and characterization of
      hyperthermostable L-asparaginase from Thermococcus kodakarensis KOD1 in
      Escherichia coli BLR(DE3). The recombinant 6* His-tagged protein L-asparaginase
      from T. kodakarensis (TkAsn), was purified to homogeneity by heat treatment
      followed by affinity chromatography using a nickel-nitrilotriacetic acid (Ni-NTA)
      column. The molecular mass of the purified enzyme was found to be approximately
      37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
      The enzymatic properties, such as optimum temperature and pH, were 90  degrees C
      and 8.0, respectively. Its appearent Km , Vmax , and Kcat values were 2.6 mM,
      1121 umol min(-1)  mg(-1) , and 694 S(-1) , respectively. The enzyme displayed
      high thermal stability at optimum temperature with an insignificant loss in
      enzymatic activity, retaining almost 90% of its activity over a time period of 32
      h. The relative activity of the enzyme was significantly inhibited by the
      supplementation of Cu(2+) and Ni(2+) ions, while moderately inhibited by other
      ions. In contrast, Mg(2+) ions enhanced the relative activity compared to the
      control. The acrylamide contents in baked dough were reduced to sixty percent
      after treatment with recombinant TkAsn as compared to the untreated control.
      Results of the present study revealed that the enzyme was highly active at
      broader range of temperatures and pH, which reflect the potential of recombinant
      TkAsn in the food processing industry. In addition, the high thermal stability of
      the enzyme may facilitates its handling, storage, and transportation.

PMID- 24442711
TI  - The barley Frost resistance-H2 locus.
AB  - Frost resistance-H2 (Fr-H2) is a major QTL affecting freezing tolerance in
      barley, yet its molecular basis is still not clearly understood. To gain a better
      insight into the structural characterization of the locus, a high-resolution
      linkage map developed from the Nure * Tremois cross was initially implemented to
      map 13 loci which divided the 0.602 cM total genetic distance into ten
      recombination segments. A PCR-based screening was then applied to identify
      positive bacterial artificial chromosome (BAC) clones from two genomic libraries
      of the reference genotype Morex. Twenty-six overlapping BACs from the integrated
      physical-genetic map were 454 sequenced. Reads assembled in contigs were
      subsequently ordered, aligned and manually curated in 42 scaffolds. In a total of
      1.47 Mbp, 58 protein-coding sequences were identified, 33 of which classified
      according to similarity with sequences in public databases. As three complete
      barley C-repeat Binding Factors (HvCBF) genes were newly identified, the locus
      contained13 full-length HvCBFs, four Related to AP2 Triticeae (RAPT) genes, and
      at least five CBF pseudogenes. The final overall assembly of Fr-H2 includes more
      than 90 % of target region: all genes were identified along the locus, and a
      general survey of Repetitive Elements obtained. We believe that this gold
      standard sequence for the Morex Fr-H2 will be a useful genomic tool for
      structural and evolutionary comparisons with Fr-H2 in winter-hardy cultivars
      along with Fr-2 of other Triticeae crops.

PMID- 24442712
TI  - Anxiety in early pregnancy: prevalence and contributing factors.
AB  - Antenatal anxiety symptoms are not only a health problem for the expectant
      mother. Research has found that maternal anxiety may also have an impact on the
      developing baby. Therefore, it is important to estimate the prevalence of
      maternal anxiety and associated factors. The current study aims to estimate the
      prevalence of anxiety symptoms during the first trimester of pregnancy and to
      identify associated risk factors. Secondly, to investigate other factors
      associated with anxiety during early pregnancy including fear of childbirth and a
      preference for cesarean section. In a population-based community sample of 1,175
      pregnant women, 916 women (78%) were investigated in the first trimester
      (gestation week 8-12). The Hospital Anxiety Depression Scale (HADS-A) was used to
      measure anxiety symptoms. The prevalence of anxiety symptoms (HADS-A scores>=8
      during pregnancy) was 15.6% in early pregnancy. Women under 25 years of age were
      at an increased risk of anxiety symptoms during early pregnancy (OR 2.6, CI 1.7
      4.0). Women who reported a language other than Swedish as their native language
      (OR 4.2, CI 2.7-7.0), reported high school as their highest level of education
      (OR 1.6, CI 1.1-2.3), were unemployed (OR 3.5, CI 2.1-5.8), used nicotine before
      pregnancy (OR 1.7, CI 1.1-2.5), and had a self-reported psychiatric history of
      either depression (OR 3.8, CI 2.6-5.6) or anxiety (OR 5.2, CI 3.5-7.9) before
      their current pregnancy were all at an increased risk of anxiety symptoms during
      early pregnancy. Anxiety symptoms during pregnancy increased the rate of fear of
      birth (OR 3.0, CI 1.9-4.7) and a preference for cesarean section (OR 1.7, CI 1.0
      2.8). Caregivers should pay careful attention to history of mental illness to be
      able to identify women with symptoms of anxiety during early pregnancy. When
      presenting with symptoms of anxiety, the women might need counseling and or
      treatment in order to decrease her anxiety.

PMID- 24442714
TI  - Site-specific proportion cured models applied to cancer registry data.
AB  - PURPOSE: Proportion-cured models were applied to evaluate their applicability on
      data from a relatively small cancer registry and to assess the up-to-date
      survival level of major cancer types in Tyrol, Austria. METHODS: In total, the 25
      most common types of cancer were analyzed with mixture cure models using the
      period approach for estimation of the proportion cured and median survival time
      of the fatal cases. RESULTS: For several of the cancer types, no estimates could
      be obtained. The models converged for 14 sites among females and for 15 among
      males. The highest estimate of the proportion cured was found for cervix cancer
      (74.0 %; 95 % CI 64.4-83.6) and the lowest for male pancreas cancer (4.6 %; 95 %
      CI 0.2-9.0). The highest median survival of the uncured was 2.7 years (95 % CI
      1.2-6.0) for male larynx cancer and the lowest 0.3 years (95 % CI 0.1-0.6) for
      male acute myeloblastic leukemia (AML). CONCLUSIONS: The estimates seem reliable
      for stomach, colon, rectum, pancreas, lung, cervix, ovary, central nervous
      system/brain and AML cancer and among men also for head/neck, esophagus, liver
      and kidney cancer. Altogether, it is demonstrated that even data from a regional
      cancer registry covering a rather small region can be utilized to derive up-to
      date survival estimates of various cancer types, enabling monitoring of the
      development and changes in cancer treatment. Moreover, potentially this
      methodology is advantageously employable in any situation where the number of
      cancer cases is limited.

PMID- 24442713
TI  - Angiotensin II-derived reactive oxygen species promote angiogenesis in human late
      endothelial progenitor cells through heme oxygenase-1 via ERK1/2 and AKT/PI3K
      pathways.
AB  - Angiotensin II (Ang II), the main component of renin-angiotensin system, could
      mediate pathogenic angiogenesis in cardiovascular disorders. Late endothelial
      progenitor cells (EPCs) possess potent self-renewal and angiogenic potency
      superior to early EPCs, but few study focused on the cross-talk between Ang II
      and late EPCs. We observed that Ang II could increase reactive oxygen species
      (ROS) and promote capillary formation in late EPCs. Ang II-derived ROS could also
      upregulate heme oxygenase-1 (HO-1) expression, and treating late EPCs with HO-1
      small interfering RNA or heme oxygenase inhibitor (HO inhibitor) could inhibit
      Ang II-induced tube formation and increase ROS level and apoptosis rate. In
      addition, PD98059 and LY294002 pretreatment attenuated Ang II-induced HO-1
      expression. Accordingly, Ang II-derived ROS could promote angiogenesis in late
      EPCs by inducing HO-1 expression via ERK1/2 and AKT/PI3K pathways, and we believe
      HO-1 might be a promising intervention target in EPCs due to its potent
      proangiogenic, antioxidant, and antiapoptosis potentials. 

PMID- 24442715
TI  - Quantitating skin fibrosis: innovative strategies and their clinical
      implications.
AB  - Skin fibrosis is the final outcome of a variety of pathologic processes ranging
      from aberrant wound healing (keloids) to environmentally induced conditions
      (nephrogenic systemic fibrosis) to idiopathic or autoimmune conditions (morphea
      and systemic sclerosis). The quantitative assessment of skin fibrosis has been a
      major burden of clinical and biomarker research in the field for the past three
      decades. Here, we review the efforts that reached some sort of validation and the
      ones we envisage have the potential for further development focusing on systemic
      sclerosis as prototype of fibrotic disease. 

PMID- 24442716
TI  - Critical evaluation of different objective techniques of nasal airway assessment:
      a clinical review.
AB  - Objective tests for the nasal volume flow are needed for the assessment of nasal
      patency for diagnosis, documentation and medicolegal purposes. Three main
      techniques are nowadays established: active anterior rhinomanometry (AAR), 4
      phase rhinomanometry (4PR) and acoustic rhinometry (AR). Several guidelines and
      consensus reports and the International Committee on Standardization have
      clarified the field of interest and the limitations of this technology. In the
      meantime, technical progress and the development of seemingly new methods have
      brought up many new facts which necessitate the re-evaluation of the test
      available. From our method of critical analysis we can conclude that AAR can be
      still considered as the standard technique for the objective assessment of the
      nasal airway. AR is a valid technique with limitations and cannot replace AAR
      because it measures different parameters thus forming a complementary technique.
      4PR might provide supplementary information although not yet all open technical
      and mathematical inconsistencies conjoint with this technique have been
      clarified. Still the individual subjective sensations of the patient do not
      always match the objective measurements. In conclusion, a combination of
      information given by the patient, the rhinoscopic findings and the carefully
      interpreted results of AAR and AR will increase considerably the success of
      surgical interventions and the feeling of satisfaction by the patient after
      surgery, when matched thoughtfully. 

PMID- 24442717
TI  - Arabidopsis thaliana NAC083 protein interacts with Mungbean yellow mosaic India
      virus (MYMIV) Rep protein.
AB  - Geminiviral replication initiator protein (Rep) is a key player in geminiviral
      rolling circle mode of replication. However, the virus exploits various host
      cellular machineries for its replication. Study of these host factors is
      important to understand the geminiviral DNA replication in greater details. With
      this view, we screened for the peptides interacting with the Rep protein of a
      representative of geminivirus, namely, Mungbean yellow mosaic India virus
      (MYMIV), employing phage display technique. Through this screen, we have
      identified a host transcription factor, NAC083, as a potential MYMIV-Rep-binding
      partner. In silico docking studies also suggested possible binding of NAC083
      peptide to MYMIV-Rep. We validated the interaction between MYMIV-Rep and
      Arabidopsis thaliana full-length NAC083 protein using in vitro pull-down assay
      and yeast two-hybrid analysis. NAC proteins are well-known transcription factors
      belonging to the largest gene families in plants. This study demonstrates for the
      first time the interaction of NAC083, a member of NAC transcription factor
      family, with MYMIV-Rep protein thereby indicating its possible role in MYMIV DNA
      replication. 

PMID- 24442718
TI  - A novel finding for enterovirus virulence from the capsid protein VP1 of EV71
      circulating in mainland China.
AB  - Enterovirus 71 (EV71) is a neurotropic virus that causes various clinical
      manifestations in young children, ranging from asymptomatic to fatal. Different
      pathotypes of EV71 notably differ in virulence. Several virulence determinants of
      EV71 have been predicted. However, these reported virulence determinants could
      not be used to identify the EV71 strains of subgenotype C4, which mainly
      circulate in China. In this study, VP1 sequences of 37 EV71 strains from severe
      cases (SC-EV71) and 192 EV71 strains from mild cases (MC-EV71) in mainland China
      were analyzed to determine the potential virulence determinants in the capsid
      protein VP1 of EV71. Although most SC-EV71 strains belonged to subgenotype C4a,
      no specific genetic lineages in C4a were correlated with EV71 virulence.
      Interestingly, amino acid substitutions at nine positions (H22Q, P27S, N31S/D,
      E98K, E145G/Q, D164E, T240A/S, V249I, and A289T) were detected by aligning the
      VP1 sequences of the SC-EV71 and MC-EV71 strains. Moreover, both the constituent
      ratios of the conservative or mutated residues in the MC-EV71 and SC-EV71 strains
      and the changes in the VP1 3D structure resulting from these mutations confirmed
      that the conservative residues (22H, 249V, and 289A) and the mutated residues
      (27S, 31S/D, 98K, 145G/Q, 164E, and 240A/S) might be potential virulence
      determinants in VP1 of EV71. Furthermore, these results led to the hypothesis
      that VP1 acts as a sandwich switch for viral particle stabilization and cellular
      receptors attachment, and specific mutations in this protein can convert mild
      cases into severe cases. These findings highlight new opportunities for
      diagnostic and therapeutic interventions.

PMID- 24442719
TI  - Multigeneration impacts on Daphnia magna of carbon nanomaterials with differing
      core structures and functionalizations.
AB  - Several classes of contaminants have been shown to have multigenerational impacts
      once a parental generation has been exposed. Acute and chronic toxicity are
      described for several types of nanomaterials in the literature; however, no
      information is available on the impact of nanomaterials on future generations of
      organisms after the exposure is removed. In the present study, the authors
      examined the impacts of carbon nanomaterials (CNMs), including fullerenes (C60),
      single-walled carbon nanotubes (SWCNTs), and multiwalled carbon nanotubes
      (MWCNTs) with neutral, positive, and negative functional groups to F1 and F2
      generation daphnids after an F0 exposure. Data from the present study indicate
      that multigenerational toxicity is present with certain nanomaterial exposures
      and is highly dependent on the surface chemistry of the nanomaterial. Many CNMs
      that showed toxicity to exposed F0 daphnids in previous experiments did not
      induce multigenerational toxicity. Certain nanomaterials, however, such as C60
      malonate, SWCNTs, SWCNT-CONH2 , and MWCNTs, caused a significant decrease in
      either survival or reproduction in F1 daphnids; and SWCNT-CONH2 decreased
      reproduction out to the F2 generation. Impacts of nanomaterials on F1 and F2 size
      were small and lacked clear patterns, indicating that CNMs have minimal
      multigenerational impacts on size. Industries should take into account how
      surface chemistry influences nanomaterial toxicity to future generations of
      organisms to create sustainable nanomaterials that do not harm freshwater
      ecosystems.

PMID- 24442720
TI  - Successful treatment of AIDS-associated, primary CNS lymphoma with rituximab- and
      methotrexate-based chemotherapy and autologous stem cell transplantation.

PMID- 24442721
TI  - The 2004 Indian Ocean tsunami catastrophe, its survivors, job and the universal
      features of suffering: a theoretical study.
AB  - The purpose of this theoretical article is to discuss the existential and
      universal feature of suffering--as illustrated by Job's suffering in the Book of
      Job in the Bible and by the survivors of the 2004 Asian tsunami catastrophe--and
      to highlight its significance for health care. Further, the study is aiming at
      contributing to health professionals' understanding of patients' suffering. The
      sources are narratives, comprising Job's book, TV interviews 1 year after the
      tsunami catastrophe and the survivors' autobiographies. The methodological
      approach is a philosophical analysis. The existential, universal, ontological and
      epistemological aspects of suffering are carefully scrutinized to unveil the
      universal and existential versus culture-specific features of suffering. Based on
      the results, the authors' recommendations are (1) a holistic concept of the
      patient and health care has to seriously consider suffering in all its complexity
      because when a person is in pain, it is not his/her body but the whole person as
      a unity of body, psyche and spirit that suffers and (2) suffering should be seen
      as the most central concept of health care, which should provide treatment for
      physical pain and all dimensions of suffering: physical, social, mental and
      spiritual aspects.

PMID- 24442722
TI  - The pathologist's identity: an insight.

PMID- 24442724
TI  - Dihydrobiphenylenes through ruthenium-catalyzed [2+2+2] cycloadditions of ortho
      alkenylarylacetylenes with alkynes.
AB  - A new synthetic route to dihydrobiphenylenes has been developed. The process
      involves a mild Ru(II) -catalyzed [2+2+2] dimerization of ortho
      alkenylarylacetylenes or its more versatile variant, the Ru-catalyzed [2+2+2]
      cycloaddition of ortho-ethynylstyrenes with alkynes. Mechanistic aspects of this
      [2+2+2] cycloaddition are discussed. 

PMID- 24442723
TI  - Sequence variation and structural conservation allows development of novel
      function and immune evasion in parasite surface protein families.
AB  - Trypanosoma and Plasmodium species are unicellular, eukaryotic pathogens that
      have evolved the capacity to survive and proliferate within a human host, causing
      sleeping sickness and malaria, respectively. They have very different survival
      strategies. African trypanosomes divide in blood and extracellular spaces,
      whereas Plasmodium species invade and proliferate within host cells. Interaction
      with host macromolecules is central to establishment and maintenance of an
      infection by both parasites. Proteins that mediate these interactions are under
      selection pressure to bind host ligands without compromising immune avoidance
      strategies. In both parasites, the expansion of genes encoding a small number of
      protein folds has established large protein families. This has permitted both
      diversification to form novel ligand binding sites and variation in sequence that
      contributes to avoidance of immune recognition. In this review we consider two
      such parasite surface protein families, one from each species. In each case,
      known structures demonstrate how extensive sequence variation around a conserved
      molecular architecture provides an adaptable protein scaffold that the parasites
      can mobilise to mediate interactions with their hosts. 

PMID- 24442725
TI  - On MegaBrain Projects.

PMID- 24442726
TI  - The DNA of socially responsible innovation: Social and natural scientists need to
      establish mutual understanding and a common language to efficiently work
      together.

PMID- 24442728
TI  - The root cap and control of root elongation in Zea mays L. seedlings exposed to
      white light.
AB  - Light-induced inhibition of the elongation of primary roots of Zea mays seedlings
      is dependent upon the perception of light by the root cap. Separate exposure of
      detached root caps and roots from which root caps have been removed (i.e.
      decapped roots) to white light or darkness has shown that the elongation of a
      dark-exposed root to which a light-exposed root cap is attached is inhibited
      significantly, whilst a light-exposed decapped root to which a dark-exposed root
      cap is attached is not inhibited. Thus the decapped root is not capable of
      perceiving the growth-inhibitory stimulus of white light and its rate of
      elongation is greater than that of light-exposed roots with root caps still
      intact. However, the capacity to perceive light and, therefore, to be inhibited
      by it, is restored to the decapped root approximately 5 h after removal of the
      root cap.Abscisic acid and two unidentified growth-inhibiting compounds are
      present in the root caps of light-grown but not of dark-grown Zea mays seedlings
      and a period of 2.5-3.0 h is required for transport of the compounds, in levels
      effective in growth inhibition, from the root cap into the apex of the root. 

PMID- 24442729
TI  - On the formation of glycolate in photosynthesizing Chlorella using a new gas
      liquid chromatography method.
AB  - Suspensions of Chlorella vulgaris were allowed to photosynthesise with two
      concentrations of (14)CO2 (101 and 543 ppm) in 80% oxygen, and the incorporation
      of (14)C into glycolate and 3-phosphoglyceric acid (3-PGA) was followed. The
      relative specific activity (RSA) of the glycolate formed at both CO2
      concentrations decreased initially and then increased slowly. The RSA of
      glycolate was much lower when the suspension photosynthesised in 101 ppm (14)CO2
      compared to 543 ppm. The RSA of 3-PGA was nearly always lower than that of
      glycolate and the results suggest that refixed dark respiratory CO2 or
      respiratory 3-PGA, or both, substantially contribute to the total 3-PGA in the
      algae. It is concluded that glycolate is formed from recent photosynthate as well
      as from storage material, but the relative contribution of these substrates
      depends on the conditions under which the algae are grown, as well as those
      obtaining at the time of glycolate excretion. 

PMID- 24442730
TI  - Late-formed metaphloem sieve-elements in Zea mays L.
AB  - Late-formed metaphloem sieve-elements in the vascular bundles of the leaf and
      pedicels of Zea differ from the typical sieve elements by having thicker cell
      walls and larger, elongate plastids. The plastids contain a quasi-crystalline
      structure which is different from that observed in the spherical plastids of
      sieve elements of other monocotyledons. 

PMID- 24442731
TI  - [The role of the epidermis in light-and temperature-induced phase-shifting of
      circadian leaf movements].
AB  - The light-induced phase-response curves of circadian leaf movements of Solanum
      nigrum and Lycopersicon esculentum differ from each other. The light-induced
      phase-response curve of the monectochimera Solanum koelreuterianum (Lycopersicon
      esculentum with the epidermis from Solanum nigrum) is different from that of
      either of the constituent species, but shows more similarities with the light
      induced phase-response curve of Lycopersicon esculentum. The differences between
      Solanum koelreuterianum and Lycopersicon esculentum are in the quality and
      especially in the range of the phase-shifting.The temperature-induced phase
      response curves of Solanum nigrum and Lycopersicon esculentum are similar to the
      light-induced ones. However, the light-and temperature-induced phase-response
      curves of the chimera Solanum koelreuterianum differ markedly from each other.The
      temperature-induced phase-response curve of the chimera Solanum koelreuterianum
      differs from that of Solanum nigrum, but is identical with the temperature
      induced phaseresponse curve of Lycopersicon esculentum.These results offer
      reasons to attribute a decisive role to the epidermis in the perception of the
      phase-shifting light but none in the temperature influence. 

PMID- 24442732
TI  - Control of synthesis de novo of ascorbate oxidase in the mustard seedling
      (Sinapis alba L.) by phytochrome.
AB  - Density-labelling with deuterium oxide has been used to distinguish preexisting
      from newly made ascorbate oxidase (EC 1.10.3.3) molecules in cotyledons of the
      mustard seedling (Sinapis alba L.). The time course of the change in bandwidth of
      isopycnically banded enzyme, taken together with the accompanying shifts in
      density, showed that the enzyme was synthesized de novo, was continuously turning
      over, and had a halt-life of about 1.25 days in darkness. Phytochrome-mediated
      increases in enzyme activity were accompanied by (i) a faster rate of labelling
      and (ii) faster progression of the profile to that of a uniformly labelled
      population, than in dark controls run in parallel. The conclusion is drawn, that
      phytochrome regulates the rate of synthesis de novo of the protein moiety of
      ascorbate oxidase in the mustard seedling. 

PMID- 24442733
TI  - Ethylene and buoyancy control rachis elongation of the semi-aquatic fern
      Regnillidium diphyllum.
AB  - When fronds of the semi-aquatic fern Regnillidium diphyllum Lindman are submerged
      the rachi elongate much more than when in contact with the air. Submergence
      appears to have two consequences that account for the enhanced elongation.
      Firstly, ethylene accumulates in the tissue and secondly, the hollow fronds are
      buoyed upward from the rhizome, continuously creating a tension in the rachi. The
      effect of ethylene is a rapid enhancement of cell elongation. It is suggested
      that ethylene softens the cell walls which are then stretched by the tensile
      force resulting from buoyancy. 

PMID- 24442734
TI  - Variation and metabolism of abscisic acid in pea seedlings during and after water
      stress.
AB  - When pea seedlings lose about 5% of their water content the abscisic acid ((+)
      ABA) level of the shoots increases ca. 20 times and the level of bound ABA, in
      all probability ABA-glucose, ca.7-10 times. After watering both ABA and bound ABA
      contents decrease within 24-48 h to the level in the control plants.After
      application of (+/-)-[2-(14)C] ABA to wilted pea shoots at the time of watering
      radioactive substances appear in the water-soluble, ether-insoluble fraction of
      ethanolic extracts and increase with time whereas radioactivity in the acidic
      ether fraction decreases. The neutral ether fraction remains free of
      radioactivity. Three radioactive zones, A, B, and C, are seen on chromatograms of
      the water-soluble fraction. A increases considerably within the entire
      experimental time, whereas B increases in the first 4-8 h after application and
      subsequently decreases. The third substance, C, which releases free ABA after
      hydrolytic treatment, does not change during the experiment. Chromatograms of the
      acidic ether fraction yield ABA and a substance staying at the origin, possibly
      phaseic acid and/or dihydrophaseic acid. Only the activity of ABA decreases
      during the experiment. 

PMID- 24442735
TI  - The role of gibberellic acid in the hydrolysis of endosperm reserves in Zea mays.
AB  - Excised maize (Zea mays L.) endosperms incubated in buffer rapidly degrade their
      starch and protein reserves. These processes are not markedly stimulated by
      addition of gibberellic acid (GA3). However protease and alpha-amylase production
      are strongly inhibited by abscisic acid, and this inhibition can be overcome by
      exogenous GA3. Endosperms of a dwarf mutant maize (d 5), which is deficient in
      endogenous GA, produce only small amounts of protease and alpha-amylase. With
      these mutants oxogenous GA3 causes a 3-5fold stimulation in hydrolase production.
      Our interpretation of these results is that in many cases maize endosperms
      contain sufficient gibberellin to stimulate maximal hydrolase production and
      starch and protein breakdown. 

PMID- 24442736
TI  - [[(3)H]thymidine incorporation and DNA-synthesis in Funaria hygrometrica].
AB  - Incubation of caulonema filaments of the moss Funaria hygrometrica with
      [(3)H]methylthymidine followed by autoradiography fails to show the real amount
      of DNA-synthesis. Especially nuclei of steadily growing tip cells remain
      unlabelled, whereas basic cells become radioactive. This effect is not based on
      different permeabilities. Autoradiographic results of experiments with 5
      fluordesoxyuridine and cycloheximide lead to the conclusion that there exists a
      marked thymidine-kinase gradient along the filament which depends on age and
      position of the cells. 

PMID- 24442737
TI  - The effect of pretreatment temperature on the exudation of xylem sap by detached
      barley root systems.
AB  - Roots of barley (Hordeum vulgare L.) plants which had been grown at 20 degrees 
      were cooled to temperatures of 12 degrees  C or lower for 1-5 days and then
      returned to 20 degrees  C when measurements were made of ion and water movement
      into the xylem after excision. Very marked increases in exudation were observed
      in cooled roots, sometimes as much as four times greater than in controls kept at
      20 degrees  C throughout their life. There were no consistent increases in the
      concentration of K(+), Ca(2+) or H2PO4' in the exudate from cooled roots and it
      was concluded that the extra water flow across the root occurred without any
      increase in the osmotic potential of the sap.Similar changes in ion absorption
      and translocation were found in intact plants transpiring either rapidly or
      slowly.Cooled roots contained appreciably more soluble carbohydrate than controls
      and when they were returned to 20 degrees  C their respiration was 50-120%
      greater. These changes were not, however, strictly correlated with differences in
      exudation in cooled and untreated roots. Cooled plants which had been heavily
      shaded respired at the same rate as controls but exuded sap at twice the rate.It
      is concluded that the effects of cooling on both exudation and the accumulation
      of roluble carbohydrate are consequences of reduced growth and the possible
      alteration of the selative amounts of growth substances in the root. 

PMID- 24442738
TI  - Bud formation in Funaria hygrometrica: A comparison of the activities of three
      cytokinins with their ribosides.
AB  - The activities of the cytokinins benzyladenine (BA), 6-(3-methylbut-2
      enylamino)purine (IPA) and zeatin in promoting bud formation in protonemata of
      Funaria hygrometrica (L.) Sibth. were compared to the biological activities of
      the corresponding ribosides. Cytokinins were found to have considerably higher
      hormonal activity as free bases than as ribosides. This observation will be
      discussed in relation to the chemical identity of the celldivision factor (CDF)
      isolated from crown gall tumors of Vinca rosea L. 

PMID- 24442741
TI  - The role of the psychiatrist : defining methods, theories, and practice in the
      time of managed care.
AB  - This essay proposes that the division between biological and psychotherapy
      oriented psychiatry originates in the discipline's reliance on two fundamentally
      different methods of inquiry, that is, the medical-biological and the empathic
      narrative. These terms are defined and distinguished from psychotherapy and
      psychodynamic psychiatry, as well as from general humanistic qualities in
      medicine. The division within the field may be fueled by a lack of clarity with
      respect to these concepts. The author argues that the essence of psychiatry is
      defined by a balanced combination of both methods. Psychiatry does not consist
      only of basic methods, but also of rules and guidelines for clinical practice,
      and of knowledge and theories used in the application of the methods. The role
      expectations for psychiatry in the managed care environment are examined and
      their effects upon methods, theory, and practice are analyzed. Some suggestions
      for dealing with the challenges of health care reform are offered. 

PMID- 24442739
TI  - Physician barriers to successful implementation of US Preventive Services Task
      Force routine HIV testing recommendations.
AB  - In 2006, the US Centers for Disease Control and Prevention issued recommendations
      supporting routine HIV testing in health care settings for all persons aged 13 to
      64 years. Despite these recommendations, physicians are not offering HIV testing
      routinely. We apply a model that has previously identified 3 central, inter
      related factors (knowledge-, attitude-, and behavior-related barriers) for why
      physicians do not follow practice guidelines in order to better understand why
      physicians are not offering HIV testing routinely. This model frames our review
      of the existing literature on physician barriers to routine HIV testing. Within
      the model, knowledge barriers include lack of familiarity or awareness of
      clinical recommendations, attitude barriers include lack of agreement with
      guidelines, while behavioral barriers include external barriers related to the
      guidelines themselves, to patients, or to environmental factors. Our review
      reveals that many physicians face these barriers with regards to implementing
      routine HIV testing. Several factors underscore the importance of determining how
      to best address physician barriers to HIV testing, including: provisions of the
      Affordable Care Act that are likely to require or incentivize major payers to
      cover HIV testing, evidence which suggests that a physician's recommendation to
      test for HIV is a strong predictor of patient testing behavior, and data which
      reveals that nearly 20% of HIV-positive individuals may be unaware of their
      status. In April 2013, the US Preventive Services Task Force released a
      recommendation supporting routine HIV testing; strategies are needed to help
      address ongoing physician barriers to testing. 

PMID- 24442742
TI  - Supervisor evaluation : from theory to implementation.
AB  - The evaluation of supervisors and assessment of teaching effectiveness are vital
      for academic psychiatry programs. The literature on teaching evaluation in
      classroom settings is reviewed briefly, followed by a summary of the available
      literature on supervisor evaluation in clinical medicine and psychiatry. While
      student evaluation forms of supervisor's teaching ability may be reliable and
      valid, this popular form of assessment is insufficient to fulfill all the
      purposes required of such evaluations. The development and implementation of a
      new process for supervisor evaluation is described for the University of
      Toronto's Department of Psychiatry. 

PMID- 24442743
TI  - Teaching psychiatry? Let hollywood help! : suicide in the cinema.
AB  - Commercial films on videotape may be helpful in teaching medical students and
      residents about psychiatry. Recommendations are made on the use of specific films
      to illustrate various aspects of suicide, including depression, posttraumatic
      stress disorder, adolescent pressures and suicide, suicide gesture vs. suicide
      attempt, and the spiritual and philosophical aspects of suicide. In the Appendix,
      the authors list several dozen films depicting suicide that might be used for
      teaching purposes. 

PMID- 24442744
TI  - Medical school electives and recruitment into psychiatry : a 20-year experience.
AB  - Part of psychiatry's recruitment problem is a result of defections among students
      who were planning careers in psychiatry when they entered medical school. The
      authors present data from a 20-year (1974-1993) experience at the University of
      Maryland that shows that students who expressed a preference for psychiatry as a
      career in the freshman year were four times more likely to enter psychiatric
      residency training after graduation if they participated in the Combined
      Accelerated Program in Psychiatry (CAPP), a 4-year psychiatric elective program,
      than if they pursued the regular undergraduate psychiatric program. More than 20%
      of the CAPP students who preferred nonpsychiatric careers as freshmen were
      "converted" to psychiatry and later entered psychiatric residency programs.
      Recent changes in the ideology and economics of our profession have neither
      lessened the popularity of the CAPP nor diminished its apparent ability to
      shelter students preferring psychiatry from the stigmatizing experiences of
      medical school. 

PMID- 24442745
TI  - Geriatric training in adult psychiatry residency training programs.
AB  - The authors surveyed all Accreditation Council for Graduate Medical Education
      accredited psychiatry residency training programs in the United States to
      determine 1) the type and amount of geriatric training provided, and 2)
      differences in the programs that door do not offer geriatric training for
      residents. Substantial geriatric training was offered in 50.7% of all programs.
      Compared with the programs without geriatric training, these programs were more
      likely to be in a Psychiatry Department, with a Division of Geriatric Psychiatry
      and/or a geriatric fellowship program. These data suggest that current geriatric
      training in many psychiatry residency programs is inadequate to prepare residents
      for treating elderly patients and to encourage residents to pursue careers in
      geriatric psychiatry. 

PMID- 24442748
TI  - Using video for psychiatric residency recruitment.

PMID- 24442746
TI  - Psychiatry residency recruitment: using the internet.

PMID- 24442749
TI  - Point : the top 10 reasons for psychopharmacology supervision.

PMID- 24442750
TI  - Counterpoint : psychopharmacology supervision.

PMID- 24442751
TI  - Educational computing : column debut.

PMID- 24442752
TI  - A thermo-stable lysine aminopeptidase from Pseudomonas aeruginosa: Isolation,
      purification, characterization, and sequence analysis.
AB  - Pseudomonas aeruginosa NJ-814, isolated from garden soil, produced an
      extracellular aminopeptidase that was purified using ammonium sulfate
      precipitation and ion exchange chromatography. The purity was confirmed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and the Mr value of
      the enzyme was estimated to be 55 kDa. The purified enzyme shows maximum activity
      at pH 9.0 and 80  degrees C. It exhibits high thermo-stability. Half of the
      activity can remain after incubation at 80  degrees C for 119 min. It is stable
      within pH range of 7.5-10.5. It is strongly activated by Co(2+) and inhibited by
      Fe(2+) , Cu(2+) , Ni(2+) , Zn(2+) , and ethylene diamine tetraacetic acid (EDTA).
      The specificity of the enzyme was investigated. Within several aminoacyl-p
      nitroanilines (AA-pNA), Lys-pNA is proven to be the optimal substrate. The
      Michaelis-Menten constant (Km ) of the enzyme for Lys-pNA and Leu-pNA were 2.32
      and 9.41 mM, respectively. Peptide map fingerprinting shows that the sequence of
      the enzyme is highly similar to aminopeptidase Y from P. aeruginosa 18A. It can
      be speculated that this enzyme is a Zn(2+) -dependent enzyme and contains two
      zinc ions in its active site.

PMID- 24442753
TI  - Synthesis, spectral characterization, and in vitro cellular activities of
      metapristone, a potential cancer metastatic chemopreventive agent derived from
      mifepristone (RU486).
AB  - Mifepristone (RU486) is marketed and used widely by women as an abortifacient,
      and experimentally for psychotic depression and anticancer treatments. After
      administration, metapristone is found to be the most predominant metabolite of
      mifepristone. We hypothesized that adhesion of circulating tumor cells (CTCs) to
      vascular endothelial bed is a crucial starting point in metastatic cascade, and
      that metapristone can serve as a cancer metastatic chemopreventive agent that can
      interrupt adhesion and invasion of CTCs to the intima of microvasculature. In the
      present study, we modified the synthesis procedure to produce grams of
      metapristone, fully characterized its spectral properties and in vitro cellular
      activities, including its cytostatic effects, cell cycle arrest, mitochondrial
      membrane potential, and apoptosis on human colorectal cancer HT-29 cells.
      Metapristone concentration dependently interrupted adhesion of HT-29 cells to
      endothelial cells. Metapristone may potentially be a useful agent to interrupt
      metastatic initiation.

PMID- 24442754
TI  - Is biomarker research advancing in the era of personalized medicine for head and
      neck cancer?
AB  - Recent progress in molecular biology and translational research has initiated an
      era of personalized medicine in head and neck clinical oncology. The genetic
      information defined by biomarker analysis in tumors and individuals is
      indispensable for the administration of molecular targeting agents. The epidermal
      growth factor receptor (EGFR) signaling pathway is an important therapeutic
      target in head and neck squamous cell carcinoma (HNSCC). The use of an anti-EGFR
      monoclonal antibody (mAb), cetuximab (Cmab), has been approved for the treatment
      of patients with head and neck cancer. Although KRAS mutation has been
      established as a potential biomarker for predicting the efficacy of anti-EGFR mAb
      in colorectal cancer, little is known about predictive markers for Cmab in head
      and neck cancer. Optimal predictive and prognostic markers as well as safety
      markers are required to promote the appropriate clinical use of Cmab and to
      determine malignant phenotypes in head and neck cancer. This article first
      reviews the role of EGFR signaling in HNSCC. The article then focuses on
      Ras/Raf/Mek/Erk and PTEN/PI3K/Akt signaling pathways as predictive markers for
      Cmab. Subsequently, the molecular basis and clinical outcome of human
      papillomavirus (HPV)-positive cancer is highlighted, and the potential role of
      anti-EGFR target therapy for HPV-positive HNSCC is discussed. Finally, the
      possible mechanism for resistance to anti-EGFR target therapy is reviewed, and I
      discuss approaches to overcome the resistance with reference to an ongoing
      clinical trial.

PMID- 24442757
TI  - Breathing variability and brainstem serotonergic loss in a genetic model of
      multiple system atrophy.
AB  - Breathing disorders like sleep apnea, stridor, and dysrythmic breathing are
      frequent in patients with multiple system atrophy (MSA). These observations have
      been related to neurodegeneration in several pontomedullary respiratory nuclei
      and may explain the occurrence of sudden death. In this study, we sought to
      determine whether these functional and neuropathological characteristics could be
      replicated in a transgenic model of MSA. Mice expressing human wild-type alpha
      synuclein under the control of the proteolipid promoter (PLP-alphaSYN) were
      compared with age-matched controls. Using whole-body, unrestrained
      plethysmography, the following breathing parameters were measured: inspiratory
      and expiratory times, tidal volume, expiratory volume, peak inspiratory and
      expiratory flows, and respiratory frequency. For each category, the mean,
      coefficient of variation, and irregularity score were analyzed. Brains were then
      processed for stereological cell counts of pontomedullary respiratory nuclei. A
      significant increase in the coefficient of variation and irregularity score was
      observed for inspiratory time, tidal volume, and expiratory volume in PLP
      alphaSYN mice (P < 0.05). Glial cytoplasmic inclusions were found in the
      medullary raphe of PLP-alphaSYN mice, together with a loss of serotonergic
      immunoreactivity in the raphe obscurus (P < 0.001) and pallidus (P < 0.01). There
      was a negative correlation between alpha-synuclein burden and raphe pallidus cell
      counts (P < 0.05). There was no significant neuronal loss in the pre-Botzinger
      complex. The PLP-alphaSYN mouse model replicates the breathing variability and
      part of the neuronal depletion in pontomedullary respiratory nuclei observed in
      patients with MSA. Our findings support the use of this model for future
      candidate drugs in the breathing disorders observed in MSA.

PMID- 24442756
TI  - Potential role of N-acetylcysteine in the management of substance use disorders.
AB  - There is a clear and pressing need to expand pharmacotherapy options for
      substance use disorders (SUDs) in order to improve sustained abstinence outcomes.
      Preclinical literature has demonstrated the role of glutamate in addiction,
      suggesting that new targets for pharmacotherapy should focus on the restoration
      of glutamatergic function. Glutamatergic agents for SUDs may span multiple
      addictive behaviors and help demonstrate potentially overlapping mechanisms in
      addiction. The current review will focus specifically on N-acetylcysteine (NAC),
      a safe and well-tolerated glutamatergic agent, as a promising potential
      pharmacotherapy for the treatment of SUDs across several substances of abuse.
      Building on recently published reviews of the clinical efficacy of NAC across a
      broad range of conditions, this review will more specifically discuss NAC as a
      pharmacotherapy for SUDs, devoting particular attention to the safety and
      tolerability profile of NAC, the wealth of preclinical evidence that has
      demonstrated the role of glutamate dysregulation in addiction, and the limited
      but growing clinical literature that has assessed the efficacy of NAC across
      multiple substances of abuse. Preliminary clinical studies show the promise of
      NAC in terms of safety, tolerability, and potential efficacy for promoting
      abstinence from cocaine, nicotine, and cannabis. Results from randomized clinical
      trials have been mixed, but several mechanistic and methodological factors are
      discussed to refine the use of NAC in promoting abstinence and relapse prevention
      across several substances of abuse. Further preclinical and clinical
      investigation into the use of NAC for SUDs will be vital in addressing current
      deficits in the treatment of SUDs.

PMID- 24442758
TI  - Isolated foveal hypoplasia without nystagmus.
AB  - We report the case of a 23-year-old healthy Caucasian male with isolated foveal
      hypoplasia without nystagmus. Clinical examination and spectral-domain optical
      coherence tomography demonstrated the bilateral absence of a foveal depression
      and the patient was diagnosed with isolated foveal hypoplasia. This is a rare
      condition which is probably under-diagnosed since it can exist without nystagmus
      and low vision. 

PMID- 24442759
TI  - The efficacy of topical 0.05 % cyclosporine A in patients with dry eye disease
      associated with Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune epithelitis which usually presents with
      mouth and eye dryness. Although the place of systemic drugs in
      keratoconjunctivitis sicca treatment has been discussed, the efficacy of some
      topical drugs has also been demonstrated; however, there are contradictory
      results related to topical cyclosporine A. We aimed to investigate the efficacy
      of 0.05 % topical cyclosporine A in patients with keratoconjunctivitis sicca due
      to primary and secondary SS. This prospective study included 26 patients with a
      diagnosis of primary and secondary SS who visited our rheumatology outpatient
      clinic. Keratoconjunctivitis sicca was diagnosed in all patients after they were
      examined at the outpatient clinic. Patients were given topical 0.05 %
      cyclosporine A emulsions for both eyes. We used another 20 patients with SS who
      were treated with saline solution as a control group. Subjective symptoms
      reported after 1-week and 1-month follow-up were complaints of burning and
      pricking sensation, light sensitivity and pain. Objective signs included redness,
      Schirmer test and tear break-up time. A total of 26 patients (19 female) were
      enrolled in the study with a mean age of 47.5 years and mean disease duration of
      5.2 years. In the first physical examination of patients, 23 patients had burning
      and pricking sensation, 24 had pain, 23 had light sensitivity, and 24 had red
      eyes. All subjective symptoms (burning and pricking sensation, light sensitivity
      and pain) were statistically significantly improved after 1-week and 1-month
      follow-up examinations (p = 0.0001). All objective signs (Schirmer test, tear
      break-up time, and redness) were statistically significantly improved after 1
      week and 1-month follow-up examinations (p = 0.0001). Compared with the control
      group, there was significant improvement in all parameters. It is concluded that
      topical 0.05 % cyclosporine A is an effective treatment option for
      keratoconjunctivitis sicca due to SS after a 1-month follow-up period.

PMID- 24442760
TI  - Glaucoma in southwest Nigeria: clinical presentation, family history and
      perceptions.
AB  - Knowledge of the presentation pattern of glaucoma helps in providing more
      understanding of the disease, leading to better control. The aim of this study
      was to determine the presentation pattern among newly diagnosed glaucoma patients
      in Lagos, Nigeria. This was a multicenter cross-sectional survey of newly
      diagnosed glaucoma patients, recruited over a four-week period. Socio-demographic
      characteristics, presenting history, awareness and perception on glaucoma, and
      basic examination findings were obtained. A total of 208 patients, including 90
      (43.2 %) females with a mean age of 53.9 years were recruited. One hundred and
      forty-three (68.7 %) were self-referred patients with a mean duration of symptoms
      of 2.6 years. Fifty-five (26.4 %) patients gave a history of glaucoma in at least
      one family member. Ninety-five patients (45.7 %) were aware that glaucoma can
      cause visual loss, but 69 (72.6 %) out of these believed the visual loss is
      reversible. Seventy (33.7 %) patients had been previously diagnosed with glaucoma
      elsewhere. From the 208 patients, 35.5 % had visual impairment (presenting visual
      acuity [VA] of <6/18 in the better eye), while 15.5 % were blind (presenting VA
      in better eye <3/60). Lack of glaucoma awareness, positive family history and
      illiteracy were associated with late presentation of glaucoma. Late presentation
      is still a major concern among glaucoma patients in Southwest Nigeria, and there
      is a need to intensify present efforts aimed at increasing public awareness,
      emphasising the irreversible nature of the disease, as well as encouraging at
      risk groups such as first-degree relatives to go for screening.

PMID- 24442761
TI  - Intralesional triamcinolone acetonide injection for the treatment of primary
      chalazions.
AB  - The aim of this study was to investigate the safety and efficacy of intralesional
      triamcinolone acetonide (TA) injection in the treatment of primary chalazions not
      responding to conservative treatment. Patient medical records were
      retrospectively reviewed for all consecutive patients that received intralesional
      TA injection by a single surgeon between January 2012 and March 2013 for the
      treatment of unresolved primary chalazions despite 1 month of conservative
      treatment. The dose of TA injection ranged from 2 to 6 mg (40 mg/mL) depending on
      the size of the chalazion. The main outcome measures included time to resolution,
      time to 50 % size reduction, and complications from the treatment. During the
      study period, 48 chalazions from 38 patients were treated by intralesional TA
      injection. A 50 % reduction in size was achieved in 81.3 % of chalazions in 4
      weeks and 83 % achieved complete resolution in 6 weeks. The mean time to complete
      resolution was 15.7 +/- 10.0 days. There were no complications noted from the
      injections; 14.6 % required subsequent incision and curettage and 2.1 % required
      a second TA injection for complete resolution. Intralesional TA injection is a
      safe, simple, and effective procedure for the management of primary chalazions
      and may be considered as an alternative to incision and curettage in cases not
      responding to conservative treatment.

PMID- 24442762
TI  - Sumatriptan-associated ischemic colitis: case report and review of the literature
      and FAERS.
AB  - BACKGROUND AND AIMS: Ischemic colitis (IC) is being increasingly recognized,
      although specific etiological causes are observed in a minority of patients.
      While several drugs have been associated with IC, most remain anecdotal reports.
      We recently treated a patient with IC thought to be related to sumatriptan for
      migraines, and performed a literature review along with a review of the FDA
      Adverse Event Reporting System (FAERS) database to identify additional cases.
      METHODS: A MEDLINE/PubMed literature review was conducted using standard IC
      search terms to identify published cases of sumatriptan and other related
      "triptan" drug causes of IC. In addition, through a Freedom of Information Act
      request, we reviewed the adverse gastrointestinal events linked to sumatriptan
      contained in the FAERS database for the 5-year period 12 March 2008-11 March
      2013, in order to determine whether unpublished cases might exist. Our case of IC
      was analyzed using a causality assessment tool initially developed for use in
      cases of alosetron (a 5-HT3 receptor antagonist)-related IC. RESULTS: Five
      published reports (containing a total of seven patients) describing sumatriptan
      associated IC in the English language literature were found and reviewed. Another
      four published reports of related 5-HT1 receptor agonists causing IC (razitriptan
      n = 1 and naratriptan n = 3) were also analyzed. Among spontaneous reports of
      possible IC contained in the FAERS database for sumatriptan, there were 19
      adverse events coded as "ischemic colitis" and another six coded as "intestinal
      ischemia" over a 5-year period ending March 2013, but clinical details were
      lacking. Similarly, five reports of possible IC from FAERS were mentioned in an
      earlier published report from the late 1990s. All of the published case reports
      of sumatriptan and related drugs were deemed to have the classic clinical
      findings and all recovered. There was one instance of possible recurrent IC
      symptoms in one patient re-exposed to sumatriptan, but not in another. We found
      that the IC scoring system developed for alosetron was applicable in our
      sumatriptan case. CONCLUSIONS: Among drug-related causes of IC, sumatriptan joins
      a growing list of agents with literature reports supported by the finding of
      suspected cases of IC in the FAERS database. However, the true incidence of IC
      due to sumatriptan, as well as other causes, cannot be accurately determined
      because of the likelihood of under-reporting. The structured IC scoring system
      appears to be applicable for drug-related as well as other etiological causes of
      IC.

PMID- 24442763
TI  - Laparoscopic surgical box model training for surgical trainees with no prior
      laparoscopic experience.
AB  - BACKGROUND: Surgical training has traditionally been one of apprenticeship, where
      the surgical trainee learns to perform surgery under the supervision of a trained
      surgeon. This is time consuming, costly, and of variable effectiveness. Training
      using a box model physical simulator - either a video box or a mirrored box - is
      an option to supplement standard training. However, the impact of this modality
      on trainees with no prior laparoscopic experience is unknown. OBJECTIVES: To
      compare the benefits and harms of box model training versus no training, another
      box model, animal model, or cadaveric model training for surgical trainees with
      no prior laparoscopic experience. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science
      Citation Index Expanded to May 2013. SELECTION CRITERIA: We included all
      randomised clinical trials comparing box model trainers versus no training in
      surgical trainees with no prior laparoscopic experience. We also included trials
      comparing different methods of box model training. DATA COLLECTION AND ANALYSIS:
      Two authors independently identified trials and collected data. We analysed the
      data with both the fixed-effect and the random-effects models using Review
      Manager for analysis. For each outcome, we calculated the standardised mean
      difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat
      analysis whenever possible. MAIN RESULTS: Twenty-five trials contributed data to
      the quantitative synthesis in this review. All but one trial were at high risk of
      bias. Overall, 16 trials (464 participants) provided data for meta-analysis of
      box training (248 participants) versus no supplementary training (216
      participants). All the 16 trials in this comparison used video trainers. Overall,
      14 trials (382 participants) provided data for quantitative comparison of
      different methods of box training. There were no trials comparing box model
      training versus animal model or cadaveric model training. Box model training
      versus no training: The meta-analysis showed that the time taken for task
      completion was significantly shorter in the box trainer group than the control
      group (8 trials; 249 participants; SMD -0.48 seconds; 95% CI -0.74 to -0.22).
      Compared with the control group, the box trainer group also had lower error score
      (3 trials; 69 participants; SMD -0.69; 95% CI -1.21 to -0.17), better accuracy
      score (3 trials; 73 participants; SMD 0.67; 95% CI 0.18 to 1.17), and better
      composite performance scores (SMD 0.65; 95% CI 0.42 to 0.88). Three trials
      reported movement distance but could not be meta-analysed as they were not in a
      format for meta-analysis. There was significantly lower movement distance in the
      box model training compared with no training in one trial, and there were no
      significant differences in the movement distance between the two groups in the
      other two trials. None of the remaining secondary outcomes such as mortality and
      morbidity were reported in the trials when animal models were used for assessment
      of training, error in movements, and trainee satisfaction. Different methods of
      box training: One trial (36 participants) found significantly shorter time taken
      to complete the task when box training was performed using a simple cardboard box
      trainer compared with the standard pelvic trainer (SMD -3.79 seconds; 95% CI 
      4.92 to -2.65). There was no significant difference in the time taken to complete
      the task in the remaining three comparisons (reverse alignment versus forward
      alignment box training; box trainer suturing versus box trainer drills; and
      single incision versus multiport box model training). There were no significant
      differences in the error score between the two groups in any of the comparisons
      (box trainer suturing versus box trainer drills; single incision versus multiport
      box model training; Z-maze box training versus U-maze box training). The only
      trial that reported accuracy score found significantly higher accuracy score with
      Z-maze box training than U-maze box training (1 trial; 16 participants; SMD 1.55;
      95% CI 0.39 to 2.71). One trial (36 participants) found significantly higher
      composite score with simple cardboard box trainer compared with conventional
      pelvic trainer (SMD 0.87; 95% CI 0.19 to 1.56). Another trial (22 participants)
      found significantly higher composite score with reverse alignment compared with
      forward alignment box training (SMD 1.82; 95% CI 0.79 to 2.84). There were no
      significant differences in the composite score between the intervention and
      control groups in any of the remaining comparisons. None of the secondary
      outcomes were adequately reported in the trials. AUTHORS' CONCLUSIONS: The
      results of this review are threatened by both risks of systematic errors (bias)
      and risks of random errors (play of chance). Laparoscopic box model training
      appears to improve technical skills compared with no training in trainees with no
      previous laparoscopic experience. The impacts of this decreased time on patients
      and healthcare funders in terms of improved outcomes or decreased costs are
      unknown. There appears to be no significant differences in the improvement of
      technical skills between different methods of box model training. Further well
      designed trials of low risk of bias and random errors are necessary. Such trials
      should assess the impacts of box model training on surgical skills in both the
      short and long term, as well as clinical outcomes when the trainee becomes
      competent to operate on patients.

PMID- 24442764
TI  - Awareness, perceptions and knowledge of strabismus among patients visiting a
      tertiary eye clinic in Southwest Nigeria.
AB  - The purpose of this study was to assess the perceptions, knowledge of the causes,
      implications and treatment of strabismus in a black population. This was a
      descriptive cross-sectional study utilizing a total sampling technique. Face-to
      face interviews were performed using a structured questionnaire. Socio
      demographic characteristics, awareness, perceived causes, effect and treatment of
      squint were investigated. Data was analysed using descriptive and inferential
      (bivariate and binary regression) analysis. A total of 405 respondents (49.6 %
      male, 50.4 % female) were interviewed. Ages ranged from 11 +/- 90 years (mean
      41.26 +/- 19.00). Modal age group was 17-44 (56 %). Levels of education showed
      that 22.0 % had no education, while primary, secondary and tertiary levels were
      12.6, 31.6 and 33.8 %, respectively. Approximately 75 % of patients were aware of
      strabismus. Perceived causes were unknown to 53 % while 18.0 and 12 % mentioned
      eye disease and congenital-related, respectively. There was no knowledge of
      treatment in 54 % of patients, while 21 and 25 % knew about medical and surgical
      treatment, respectively. The effects on social and family life were
      stigmatization/social misfit (23 %), psychosocial/self
      pity/depression/inferiority complex (88 %), burden (economic/time) (7 %), and
      poor cosmesis (5 %). Females were significantly more aware than males (p = 0.043,
      OR 0.6, CI 0.399-0.986). Age (p = 0.187) and level of education (p = 0.321) had
      no significant relationship with the levels of awareness. Respondents who had no
      education were 1.25 times less likely to be aware of squint than those who had
      education (OR 0.8, CI 0.693-1.642). The awareness of the cause, effects and
      treatment of strabismus is poor in this population. Females were more aware than
      males.

PMID- 24442765
TI  - Galactose treatment in focal and segmental glomerulosclerosis.

PMID- 24442766
TI  - Response: galactose treatment in focal and segmental glomerulosclerosis.

PMID- 24442767
TI  - Renal bladder ultrasound evaluation in monosymptomatic primary nocturnal
      enuresis: is it really necessary?
AB  - BACKGROUND: Published guidelines regarding radiographic imaging in the evaluation
      of monosymptomatic primary nocturnal enuresis (MPNE) are not followed. We aimed
      to evaluate the prevalence of urological abnormalities on renal/bladder
      ultrasound (RBUS) in children with MPNE and to compare the RBUS findings in
      children with and without MPNE. METHODS: Retrospective data collection in all
      children aged 5-17 years seen for the initial evaluation of MPNE. Control group
      consisted of age- and sex-matched children who had abdominal ultrasound for other
      than bladder-/kidney-related causes. RBUS findings were analyzed with regard to
      the need for intervention and/or follow-up. RESULTS: While abnormalities on RBUS
      were seen in 12.54% of enuretic children and in 5.38% of controls (p = 0.004),
      the majority of these findings were clinically insignificant. Of those with
      abnormalities, only 4 enuretic children (1.43%) required intervention and 8
      (2.87%) needed follow-up studies. These rates were not significantly different
      from the controls. However, enuretic children with RBUS abnormalities appear to
      be more resistant to treatment than enuretic children with normal RBUS (p =
      0.002). CONCLUSIONS: A small proportion of abnormalities seen on RBUS in children
      with MPNE require intervention and/or further evaluation. The identification of
      insignificant RBUS findings could lead to unnecessary additional investigations
      owing to parental concern. Detailed history and a voiding diary may be sufficient
      in the initial evaluation of children with MPNE, although RBUS may play an
      important role in patients who are resistant to treatment.

PMID- 24442768
TI  - The dynamics of interleukin-8 and its interaction with human CXC receptor I
      peptide.
AB  - Interleukin-8 (CXCL8, IL-8) is a proinflammatory chemokine important for the
      regulation of inflammatory and immune responses via its interaction with G
      protein coupled receptors, including CXC receptor 1 (CXCR1). CXCL8 exists as both
      a monomer and as a dimer at physiological concentrations, yet the molecular basis
      of CXCL8 interaction with its receptor as well as the importance of CXCL8 dimer
      formation remain poorly characterized. Although several biological studies have
      indicated that both the CXCL8 monomer and dimer are active, biophysical studies
      have reported conflicting results regarding the binding of CXCL8 to CXCR1. To
      clarify this problem, we expressed and purified a peptide (hCXCR1pep)
      corresponding to the N-terminal region of human CXCR1 (hCXCR1) and utilized
      nuclear magnetic resonance (NMR) spectroscopy to interrogate the binding of wild
      type CXCL8 and a previously reported mutant (CXCL8M) that stabilizes the
      monomeric form. Our data reveal that the CXCL8 monomer engages hCXCR1pep with a
      slightly higher affinity than the CXCL8 dimer, but that the CXCL8 dimer does not
      dissociate upon binding hCXCR1pep. These investigations also showed that CXCL8 is
      dynamic on multiple timescales, which may help explain the versatility in this
      interleukin for engaging its target receptors. 

PMID- 24442769
TI  - Pressure overloaded right ventricles: a multicenter study on the importance of
      trabeculae in RV function measured by CMR.
AB  - Cardiac magnetic resonance (CMR) imaging is the preferred method to measure right
      ventricular (RV) volumes and ejection fraction (RVEF). This study aimed to
      determine the impact of excluding trabeculae and papillary muscles on RV volumes
      and function in patients with RV pressure and/or volume overload and healthy
      controls and its reproducibility using semi-automatic software. Eighty patients
      (pulmonary hypertension, transposition of the great arteries after arterial
      switch operation and after atrial switch procedure and repaired Tetralogy of
      Fallot) and 20 controls underwent short-axis multislice cine CMR. End diastolic
      volume (EDV), end systolic volume (ESV), RV mass and RVEF were measured using 2
      methods. First, manual contour tracing of RV endo- and epi-cardial borders was
      performed. Thereafter, trabeculae were excluded from the RV blood volume using
      semi-automatic pixel-intensity based software. Both methods were compared using a
      Student T test and 25 datasets were re-analyzed for reproducibility. Exclusion of
      trabeculae resulted in significantly decreased EDV; ranging from -5.7 +/- 1.7
      ml/m(2) in controls to -29.2 +/- 6.6 ml/m(2) in patients after atrial switch
      procedure. RVEF significantly increased in all groups, ranging from an absolute
      increase of 3.4 +/- 0.8 % in healthy controls to 10.1 +/- 2.3 % in patients after
      atrial switch procedure. Interobserver agreement of method 2 was equal to method
      1 for RVEDV, RVESV and RVEF and superior for RV mass. In patients with overloaded
      RVs exclusion of trabeculae from the blood volume results in a significant change
      in RV volumes, RVEF and RV mass. Exclusion of trabeculae is highly reproducible
      when semi-automatic pixel-intensity based software is used.

PMID- 24442770
TI  - Qualitative and quantitative accuracy of ultrasound-based virtual histology for
      detection of necrotic core in human coronary arteries.
AB  - The aim was to test the accuracy of virtual histology (VH) for detecting necrotic
      core (NC) in an ex vivo human model of coronary arteries as compared to real
      histology (RH). A total of nine consecutive explanted hearts were included in the
      study. Coronary segments, clearly identified by anatomical landmarks, were
      analyzed by intravascular ultrasound (IVUS-VH) immediately after heart collection
      and thereafter by RH. NC was expressed as absolute (total amount) and relative
      (corrected for plaque area) values. Correlation analysis was performed using
      linear regression models at cross-section level, with correction for repeated
      measurements per patient, and at segment level. Receiver operator curves (ROC)
      were developed for testing accuracy of VH in detecting RH-NC. Overall, 321 mm
      were analyzed corresponding to 642 IVUS-VH frames and corresponding histological
      slices. VH and RH-NC areas were 0.24 +/- 0.43 and 0.16 +/- 0.43 mm(2),
      respectively (p < 0.001). At cross-section level, the correlation between VH and
      RH-NC was moderate in absolute (r = 0.50, p < 0.001) and poor in relative values
      (r = 0.43, p = 0.120). At the segment level, this correlation improves in terms
      of absolute values (r = 0.80, p = 0.01), but was not significant in terms of
      relative values (r = 0.43, p = 0.25). The ROC curve showed a C-statistics of
      0.904 (p < 0.001) with high sensitivity (94 %), but low specificity (53 %) and
      low positive predictive value (48 %). Although VH has a high sensitivity in
      identifying RH-NC, it has a low specificity and low positive predictive value. In
      addition, it is not able to accurately quantify its size within the corresponding
      histological specimen.

PMID- 24442771
TI  - Effect of blood donation-mediated volume reduction on regional right ventricular
      deformation in healthy subjects.
AB  - Strain (S) and strain rate (SR) are known to be altered in diseases associated
      with right ventricular (RV) pressure/volume overload and RV myocardial
      dysfunction; however determinants of S/SR are incompletely understood. The aim of
      this study was to examine the effect of blood donation-mediated volume reduction
      on regional RV deformation in healthy young adults. Study population was composed
      of 61 consecutive healthy subjects who were volunteers for blood donation. All
      underwent standard echocardiography and two-dimensional S and SR imaging by
      speckle tracking before and after 450 mL blood donation. We found no change in RV
      lateral wall SR in all three segments. However, the S in the apical and mid
      segments of the RV lateral wall immediately decreased after blood donation [-26.2
      +/- 3.3 vs. -23.2 +/- 3.3 % (p < 0.0001) and -28.2 +/- 3.4 vs. -27.1 +/- 3.2 % (p
      = 0.009), respectively], whereas no change was observed in the basal segment.
      Moreover, changes in systolic S on the apical segment of the RV lateral wall
      before and after blood donation were significantly correlated with the changes in
      the RV size [end-diastolic area index, r = - 0.369 (p = 0.003) and end-systolic
      area index, r = - 0.319 (p = 0.012)] and changes in the stroke volume index [r = 
      0.436 (p < 0.001)]. Blood donation-mediated volume reduction in healthy subjects
      caused a regional difference in RV longitudinal deformation with the lower mid
      and apical S that was related to parameters of volume load severity. However, RV
      systolic SR was found to be resistant to the effects of volume depletion.

PMID- 24442772
TI  - A church-based pilot study designed to improve dietary quality for rural, lower
      Mississippi Delta, African American adults.
AB  - We piloted a 6-month, church-based, behavioral intervention, Delta Body and Soul
      (DBS), for African American (AA) adults in the Lower Mississippi Delta (LMD). DBS
      was designed to improve overall dietary quality in LMD AA adults. The
      intervention included six once monthly group-based educational sessions
      implemented by trained church members. Program implementation, session
      attendance, congregational feedback, and baseline and post-intervention,
      demographic, health, behavioral, and clinical parameters were assessed.
      Participants were predominately AA, female, and overweight or obese. Retention
      rate was 79 %. High adherence, defined as attendance at four or more educational
      sessions, was associated with dietary quality improvement and reduced blood
      glucose. Implementation of the DBS pilot intervention was feasible and may result
      in dietary quality and clinical improvements.

PMID- 24442773
TI  - From bench to humans: formulation development of a poorly water soluble drug to
      mitigate food effect.
AB  - This study presents a formulation approach that was shown to mitigate the
      dramatic food effect observed for a BCS Class II drug. In vitro (dissolution), in
      vivo (dog), and in silico (GastroPlus(r)) models were developed to understand the
      food effect and design strategies to mitigate it. The results showed that such
      models can be used successfully to mimic the clinically observed food effect.
      GastroPlus(r) modeling showed that food effect was primarily due to the extensive
      solubilization of the drug into the dietary lipid content of the meal. Several
      formulations were screened for dissolution rate using the biorelevant dissolution
      tests. Surfactant type and binder amount were found to play a significant role in
      the dissolution rate of the tablet prototypes that were manufactured using a high
      shear wet granulation process. The performance of the lead prototypes (exhibiting
      best in vitro dissolution performance) was tested in dogs and human subjects. A
      new formulation approach, where vitamin E TPGS was included in the tablet
      formulation, was found to mitigate the food effect in humans. 

PMID- 24442775
TI  - Pit-field distribution, plasmodesmatal frequency, and assimilate flux in the
      mestome sheath cells of wheat leaves.
AB  - The distribution of pit fields and plasmodesmata in the mestome-sheath cells of a
      wheat leaf has been determined by study of sections and partial macerates. Each
      bundle is approximately symmetrical about the sagittal plane and most
      plasmodesmata occur in the mestome sheath where its cells abut the metaphloem.
      Plasmodesmata are absent adjacent to xylem vessels, and the frequency of
      plasmodesmata declines sharply in cells that lie close to the sagittal plane.
      Calculations show that 1 cm(2) of leaf lamina has approximately 2x10(8)
      plasmodesmatal connections to the phloem of the longitudinal veins, and that 85%
      of these connections are to the late-maturing intermediate bundles that do not
      complete their differentiation until leaf growth is nearly finished. The phloem
      area of inner tangential wall of the mestome sheath amounts to 0.26 cm(2) per
      cm(2) of leaf area and plasmodesmata occupy 1.5% of this area.These anatomical
      facts are used to estimate the sugar flux across the inner-tangential wall of the
      sheath as 2x10(2) pmol s(-1) cm(2) sheath. Further analysis strongly suggests
      that this flux must cross the sheath by diffusion through the plasmodesmata,
      creating there a flux of 1.5x10(4) pmol s(-1) cm(-2) plasmodesma. These results
      are compared with data recently obtained for the transfer-cell/sieve-element
      boundary in Vicia and are found to be about one tenth of the flux in that system,
      the transfer being adequately driven by a concentration gradient of 50 MUg cm(-3)
      of sugar across the sheath. Such a concentration gradient could be achieved by
      the photosynthetic activity of about 50 chloroplasts acting for about 2 min. The
      transverse veins that lack a mestome sheath are unlikely to account for more than
      10% of the fluxes calculated here and have been ignored in the calculations. It
      is concluded that the symplastic pathway is the only possible one for assimilate
      traffic across the mestome sheath in wheat, and that diffusion down a gradient of
      sugar concentration from the chloroplasts to the sheath acts as the driving
      force. This suggestion is reinforced by analysis of the contributions of the
      larger and smaller veins to the water flux from the same square centimetre of
      leaf. This analysis shows that 99% of the water flux must exit from the xylem of
      the 7 large bundles, presumably through the apoplast, securing an effective
      separation between the inwardly directed flow of sugar (laoded symplastically
      chiefly through the small longitudinal bundles) and the outwardly directed, very
      much larger flux of water. 

PMID- 24442774
TI  - Efficacy, pharmacokinetics, and biodistribution of thermosensitive chitosan/beta
      glycerophosphate hydrogel loaded with docetaxel.
AB  - Docetaxel (DTX) is a widely used anticancer drug for various solid tumors.
      However, its poor solubility in water and lack of specification are two
      limitations for clinical use. The aim of the study was to develop a
      thermosensitive chitosan/beta-glycerophosphate (C/GP) hydrogel loaded with DTX
      for intratumoral delivery. The in vitro release profiles, in vivo antitumor
      efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX
      C/GP) were evaluated. The results of in vitro release study demonstrated that DTX
      C/GP had the property of controlled delivery for a reasonable time span of 3
      weeks and the release period was substantially affected by initial DTX strength.
      The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing
      mice. It was found that the tumor volume was definitely minimized by intratumoral
      injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of
      blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was
      2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic
      characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP
      significantly prolonged the DTX retention and maintained a high DTX concentration
      in tumor. The amount of DTX distributed to the normal tissues was minimized so
      that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated
      controlled release and significant efficacy and exhibited potential for further
      clinical development. 

PMID- 24442776
TI  - Subcellular localization of the red-absorbing form of phytochrome by
      immunocytochemistry.
AB  - An immunocytochemical technique was used to localize the red-absorbing form of
      phytochrome at the light- or electron-microscope level in etiolated barley
      (Hordeum vulgare L.) coleoptile tip, rice (Oryza sativa L.) coleoptilar node,
      maize (Zea mays L.) coleoptile tip, rye (Secale cereale L.) coleoptile tip and
      coleoptilar node, and oat (Avena sativa L.) root cap. Staining for phytochrome in
      the cells was found to be generally distributed throughout the cytoplasm. In
      addition, barley also showed staining around the periphery of vesicles, and rice
      showed staining in numerous discrete regions in the cytoplasm. Electron
      microscopic localization studies of the nodal region of rye and the root cap of
      oat indicate staining associated with the nuclear membrane and with the interior
      of mitochondria and amyloplasts as well as general staining like that observed
      with the light microscope. Cells of the coleoptile tip of maize were unusual in
      having heavy staining associated with amyloplasts only. 

PMID- 24442777
TI  - The structure of the lettuce endosperm.
AB  - The two-cell-layered endosperm of lettuce (Lactuca sativa L.) is characterized by
      thick cell walls and dense cytoplasm. The periodic-acid-Schiff's(PAS)-positive
      cell wall forms numerous peg-like projections which extend into the cytoplasm.
      The dense cytoplasm contains organelles of protein and lipid storage. The protein
      bodies are numerous and appear to be interconnected by narrow extensions of their
      envelopes. Spherosomes are also numerous; they occupy a peripheral position in
      the cytoplasm. Other organelles typical of plant cells (nuclei with prominent
      nucleoli, mitochondria, microbodies, dictyosomes and various vesicles) are also
      found in the ground cytoplasm of the endosperm cell. Germination of the seeds
      began after 14 h imbibition in light, and by 24 h 35-40% of the seeds had
      germinated. The cell walls of endosperm from seeds germinated in light for 12-15
      h were extensively broken down as shown by the decrease in PAS staining of the
      wall. Cell-wall breakdown increased with the duration of imbibition, with the
      exception of the wall adjacent to the integument which showed no evidence of
      digestion. The structural complexity of the endosperm cell wall is correlated
      with the role this tissue plays in restricting embryo growth. Cell-wall breakdown
      is correlated with radicle protrusion, although a causal relationship between
      these two events is not proved. 

PMID- 24442778
TI  - [Effect of water stress on phosphoenolpyruvate carboxylase activity in
      Mesembryanthemum crystallinum (L.)].
AB  - Four-and-a-half-week-old plants of Mesembryanthemum crystallinum (L.) were
      transferred to cooled nutrient solution or to nutrient solution of low oxygen
      content. These stress treatments are known to reduce the absorption of water by
      plants. Examination of the second foliar leaves showed that the stress treatments
      result in a malate accumulation in the leaf mesophyll during the night which is
      paralleled by a drastically increased activity of phosphoenolpyruvate
      carboxylase. The results are discussed in relation to alterations of leaf growth,
      leaf water content and leaf water saturation deficit of the plants treated as
      described. 

PMID- 24442779
TI  - In-vivo evidence for metabolic control of amino-acid and protein synthesis by
      exogenous lysine and threonine in Mimulus cardinalis.
AB  - Young developing seedlings of Mimulus cardinalis Douglas (Scrophulariaceae) were
      grown in Hoagland's medium supplemented with lysine (LYS; 1.0 mM), threonine
      (THR; 1.0 mM), LYS+THR (1.0 mM ea.) or LYS+THR+methionine (MET; 1.0-1.0-0.1 mM,
      respectively). LYS or THR reduced the total amount of protein in the developing
      seedlings and when added in combination completely inhibited the accumulation of
      protein after 7 days. The combination of LYS+THR+MET enhanced the accumulation of
      protein. When MET was added to seedlings grown on LYS+THR for 9 days, the rate of
      protein accumulation reverted to normal. Studies using [(14)C]leucine
      demonstrated similar inhibitory patterns on protein synthesis. The effects of LYS
      and THR on the distribution of [(14)C]aspartate into the aspartate amino acids
      including MET were studied. LYS and THR, singly and synergistically when in
      combination, inhibited the synthesis of MET. Thus the simultaneous application of
      LYS and THR can be interpreted as producing an artificially induced MET
      auxotroph. These results indicate that LYS and THR act singly and together in
      vivo to inhibit the accumulation of soluble LYS, MET and THR in a manner
      indicative of end-product inhibition. Indirect evidence for end-product control
      of alanine, arginine, glycine, phenylalanine, proline, tryptophan, tyrosine and
      valine is also given. 

PMID- 24442780
TI  - [Investigation on the regulation of the glycolate-2,6-dichlorophenolindophenol
      oxidoreductase activity during greening of a Chlorella mutant].
AB  - We have examined the activity and regulation of the glycolate oxidizing enzyme in
      ten different greening stages of the Chlorella mutant Chlorella fusca C-1.1.10.10
      The mutant has lost the ability to form chlorophyll in the dark. The dark grown
      cells exposed to light need after a short lag phase about 12 hs for normal
      greening. CO2-fixation starts after 2 h of illumination.In the first 2 h of
      illumination we find a phenomenon in the induction of the enzyme activity. In the
      first hour the activity increases to a maximum and then decreases in the second
      hour to a minimum. After a recovery time the activity increases proportionally to
      the time of illumination and finally reaches a value about 8 times higher than
      that found in the normal Chlorella strain.These results are discussed with
      respect to a dual mechanism in the regulation of the enzyme activity. At the
      beginning the glycolate oxidation may be regulated by phytochrome and then by a
      substrate induction. 

PMID- 24442781
TI  - 2-Chloroethanephosphonic acid reduces transpiration and stomatal opening in
      Coffea arabica L.
AB  - Foliar sprays of 2-chloroethanephosphonic acid reduced transpiration rates per
      unit leaf area and stomatal apertures during the day in Coffea arabica L. The
      effect was first detected six hours after treatment and persisted for up to five
      days. 

PMID- 24442782
TI  - [Synthesis of heavy RNA during a cell cycle in Euglena gracilis].
AB  - In a previous investigation we had observed discontinuous RNA synthesis during
      the cell cycle of Euglena gracilis grown synchronously in the light or in the
      dark. In the present study, we analyse which RNA species are synthesized during
      the several phases of the cell cycle. During cell division, sedimentation
      analysis of RNA on sucrose gradients and polyacrylamide-agarose gel
      electrophoresis show a labeled 30 S RNA peak having a molecular weight of
      2.1x10(6) daltons. This type of RNA seems heterogeneous on the basis of its
      behaviour in polyacrylamide-agarose gel electrophoresis, and is composed of at
      least two different molecular species. Their synthesis is inhibited by
      cycloheximide (50 MUg/ml). This RNA is degraded preferentially to 13 S material.
      By autoradiography using a light microscope, we can observe extensive labeling in
      the nucleolus of dividing cells. Kinetics of labeling, chase experiments, and
      concomitant synthesis of heavier RNA (40 S and 35 S) tend to identify the 30 S
      RNA as the immediate precursor of one or both cytoplasmic ribosomal RNA
      molecules. 

PMID- 24442783
TI  - Altered morphogenesis of placental tissues of tobacco in vitro: Stigmatoid and
      carpelloid outgrowths.
AB  - When placental tissue of tobacco (Nicotiana tabacum L.) was cultured on liquid
      medium with 4% sucrose but with no hormones, many ovules, instead of maturing
      normally, grew as elongate, style-like structures with terminal stigmas. A
      limited number of these formed a proximal swelling with ovules. The significance
      of these results is discussed briefly. 

PMID- 24442784
TI  - Carbohydrate-binding proteins from the sieve-tube sap of Robinia pseudoacacia L.
AB  - Evidence is provided for the occurrence of lectins (phytohemagglutinins) in the
      sieve-tube sap of Robinia pseudoacacia L. The most potent sugars found to inhibit
      the complex formation of the soluble protein with rabbit erythrocytes were N
      acetyl-galactosamine and glycosides containing galactose. Sucrose and inositol
      had weaker effects. The extract of the membraneous material present in the sieve
      tube sap also contains lectins, but the sugar specifity is different. 

PMID- 24442785
TI  - The senescence of isolated chloroplasts.
AB  - Because previous work indicated that senescence of oat leaves in darkness
      probably centers in the cytoplasm, the senescence of chloroplasts isolated from
      the same material and carefully purified was studied. The rate of loss of
      chlorophyll was about one-tenth of that which takes place in the isolated leaves
      at the same temperature, while the loss of protein, though slightly more rapid,
      was still only 36% of the rate observed in the leaf after 7 days. This unexpected
      stability of the chloroplasts is matched by their photosynthesis, 81% of
      photosystem I and 35% of photosystem II being present after 3 days at 25 degrees
      . Traces of system I, but not of system II, were still detectable even after 7
      days. 

PMID- 24442788
TI  - DSM-5 alcohol use disorder criteria in "Crazy Heart" (2009)-a media content
      analysis with teaching purposes.
AB  - OBJECTIVE: The movie Crazy Heart (2009) draws our attention to alcohol disorders
      as it has a large number of scenes which portray alcohol consumption and fulfill
      the new DSM-5 Alcohol Use Disorder (DSM-5-AUD) criteria. In view of the recent
      launch of DSM-5, this is an appropriate opportunity to explore alcohol
      consumption in a large number of scenes employing the DSM-5-AUD criteria to study
      this. METHODS: We use media content analysis to identify DSM-5 AUD criteria as
      portrayed by the main protagonist of the movie Bad Blake in a structured manner.
      We studied his behavior and attitudes in the context of the film structure and
      storyline. RESULTS: The severity continuum of DSM-5 AUD can be demonstrated
      through the trajectory of the character Bad Blake. In the course of the movie,
      there is some reference to all the DSM-5-AUD criteria, which can be applied to
      this character within the 21 scenes selected for this study. CONCLUSION: This
      film can therefore be helpful and used to introduce students and trainees to the
      DSM-5-AUD criteria. It also allows teachers to discuss with their students and
      trainees the options of treatment including decision to quit drinking (total
      abstinence) and the recovery and relapse of this chronic condition.

PMID- 24442789
TI  - Seven hundred days of startup: a day in the life of a medical student in Silicon
      Valley.

PMID- 24442786
TI  - Proteome analysis for antifungal effects of Bacillus subtilis KB-1122 on
      Magnaporthe grisea P131.
AB  - Rice blast, caused by Magnaporthe grisea threatens rice production worldwide. It
      is important to develop novel and environment-safe strategies to control the
      fungus. Here we reported that Bacillus subtilis KB-1122 could strikingly inhibit
      the growth of M. grisea P131 in agar diffusion assays. To further understand the
      molecular mechanism on the suppressive role of B. subtilis on M. grisea, the
      antagonist-pathogen interaction of the two strains was studied by using
      comparative proteome analysis in this report. The cellular and culture
      supernatant (CSN) proteins were prepared from co-culture and subjected to two
      dimensional polyacrylamide gel electrophoresis. Proteome analysis revealed 33
      cellular and 18 CSN proteins showing changes upon co-culture respectively.
      Importantly, down-regulated cellular proteins came from M. grisea, whereas up
      regulated proteins derived from B. subtilis. Results suggested that
      glyceraldehyde-3-phosphate dehydrogenase and serine protein kinase might
      contribute to antifungal activity of B. subtilis KB-1122. Of CSN proteins
      identified, the endo-1,4-beta-glucanase (involved in degradation of
      polysaccharides) was up-regulated consistently at different times of incubation.
      This suggests that this enzyme plays an important role in the interaction between
      B. subtilis KB-1122 with M. grisea P131. 

PMID- 24442790
TI  - In vivo characterization and numerical simulation of prostate properties for non
      thermal irreversible electroporation ablation.
AB  - BACKGROUND: Irreversible electroporation (IRE) delivers brief electric pulses to
      attain non-thermal focal ablation that spares vasculature and other sensitive
      systems. It is a promising prostate cancer treatment due to sparing of the
      tissues associated with morbidity risk from conventional therapies. IRE effects
      depend on electric field strength and tissue properties. These characteristics
      are organ-dependent, affecting IRE treatment outcomes. This study characterizes
      the relevant properties to improve treatment planning and outcome predictions for
      IRE prostate cancer treatment. METHODS: Clinically relevant IRE pulse protocols
      were delivered to a healthy canine and two human cancerous prostates while
      measuring electrical parameters to determine tissue characteristics for
      predictive treatment simulations. Prostates were resected 5 hr, 3 weeks, and 4
      weeks post-IRE. Lesions were correlated with numerical simulations to determine
      an effective prostate lethal IRE electric field threshold. RESULTS: Lesions were
      produced in all subjects. Tissue electrical conductivity increased from 0.284 to
      0.927 S/m due to IRE pulses. Numerical simulations show an average effective
      prostate electric field threshold of 1072 +/- 119 V/cm, significantly higher than
      previously characterized tissues. Histological findings in the human cases show
      instances of complete tissue necrosis centrally with variable tissue effects
      beyond the margin. CONCLUSIONS: Preliminary experimental IRE trials safely
      ablated healthy canine and cancerous human prostates, as examined in the short-
      and medium-term. IRE-relevant prostate properties are now experimentally and
      numerically defined. Importantly, the electric field required to kill healthy
      prostate tissue is substantially higher than previously characterized tissues.
      These findings can be applied to optimize IRE prostate cancer treatment
      protocols.

PMID- 24442791
TI  - Survey of the utility of once-monthly bisphosphonate treatment for improvement of
      medication adherence in osteoporosis patients in Japan.
AB  - Prescription of a bisphosphonate (BP) with monthly dosing has recently been
      approved in Japan. The value of this approach for improvement of medication
      adherence was investigated in patients undergoing drug therapy for osteoporosis.
      A questionnaire was distributed to patients receiving treatment for osteoporosis
      at 8 medical facilities (5 orthopedic, 2 gynecology, and one internal medicine).
      Responses were collected from 1,300 patients. After exclusion of those who missed
      an item on the questionnaire or took drugs other than oral drugs, responses from
      1,151 patients were analyzed. The most frequently used drug for treatment of
      osteoporosis was a once-weekly BP. Of the 1,151 patients, 38.4 % reported
      forgetting to take their current drug. The most frequent concern was 'I cannot
      feel an effect', but 73.2 % answered 'I have no concerns'. Regarding the most
      appropriate dosing regimen for long-term treatment, 60.3 % selected once-weekly
      and 24 % selected once every 4 weeks. Based on a recommendation by a physician of
      a drug to be taken monthly, 32.5 % wanted to switch, 31.8 % were undecided, and
      35.7 % wanted to continue with their current drug. The desire for a change was
      higher among patients currently taking a once-weekly BP (52.3 %) than among
      patients taking a daily BP (29.5 %) or a SERM (19.4 %). This survey revealed
      patients' preferences in osteoporosis drug therapy. It is important to select a
      drug for osteoporosis based on the efficacy and the drug regimen preferred by the
      individual patient. 

PMID- 24442792
TI  - Non-destructive evaluation of chlorophyll content in quinoa and amaranth leaves
      by simple and multiple regression analysis of RGB image components.
AB  - Leaf chlorophyll content provides valuable information about physiological status
      of plants; it is directly linked to photosynthetic potential and primary
      production. In vitro assessment by wet chemical extraction is the standard method
      for leaf chlorophyll determination. This measurement is expensive, laborious, and
      time consuming. Over the years alternative methods, rapid and non-destructive,
      have been explored. The aim of this work was to evaluate the applicability of a
      fast and non-invasive field method for estimation of chlorophyll content in
      quinoa and amaranth leaves based on RGB components analysis of digital images
      acquired with a standard SLR camera. Digital images of leaves from different
      genotypes of quinoa and amaranth were acquired directly in the field. Mean values
      of each RGB component were evaluated via image analysis software and correlated
      to leaf chlorophyll provided by standard laboratory procedure. Single and
      multiple regression models using RGB color components as independent variables
      have been tested and validated. The performance of the proposed method was
      compared to that of the widely used non-destructive SPAD method. Sensitivity of
      the best regression models for different genotypes of quinoa and amaranth was
      also checked. Color data acquisition of the leaves in the field with a digital
      camera was quick, more effective, and lower cost than SPAD. The proposed RGB
      models provided better correlation (highest R (2)) and prediction (lowest RMSEP)
      of the true value of foliar chlorophyll content and had a lower amount of noise
      in the whole range of chlorophyll studied compared with SPAD and other leaf image
      processing based models when applied to quinoa and amaranth. 

PMID- 24442793
TI  - Responsiveness to erythropoiesis-stimulating agents in chronic kidney disease:
      does geography matter?
AB  - Management of renal anemia in the large and at-risk population of non-dialysis
      chronic kidney disease (CKD) patients is a critical issue. In particular,
      definition of the optimal hemoglobin (Hb) target for therapy is controversial but
      highly warranted by physicians and patients worldwide. Recently, international
      clinical practice guidelines have recommended delayed initiation of
      erythropoiesis-stimulating agents (ESA) and lower Hb target levels during
      maintenance therapy. However, geographical differences in terms of ESA dose
      needed to achieve a given Hb value can be evidenced, with US patients showing
      higher prevalence of ESA resistance. On the other hand, non-US patients are often
      maintained in a higher Hb range by means of low ESA doses. This critical point
      has never been addressed. Nevertheless, outside of the US, translating the
      restrictive recommendations of new guidelines, which are essentially based on
      trials in US patients, can lead to negative effects, such as an increased need
      for a blood transfusion, and worsening of quality of life. In this article we
      provide a reappraisal of current recommendations on anemia management in non
      dialysis CKD in light of the geographical differences in individual
      responsiveness to ESA. 

PMID- 24442794
TI  - Sofosbuvir: first global approval.
AB  - Sofosbuvir (SolvadiTM), a nucleotide analogue hepatitis C virus NS5B polymerase
      inhibitor, is under development with Gilead Sciences for the once-daily, oral
      treatment of chronic hepatitis C. Oral sofosbuvir has been approved in the US for
      the treatment of chronic hepatitis C as a component of a combination antiviral
      regimen. In addition, the European Medicines Agency's Committee for Medicinal
      Products for Human Use has recommended the approval of sofosbuvir for the
      treatment of chronic hepatitis C. This article summarizes the milestones in the
      development of sofosbuvir leading to this first approval for chronic hepatitis C.

PMID- 24442795
TI  - Impact of sleepwise: an intervention for youth with developmental disabilities
      and sleep disturbance.
AB  - The prevalence of sleep disturbance among children with developmental
      disabilities is known to be considerably higher than the typical population. The
      current study examined the effectiveness of the Sleepwise intervention program
      (O'Connell and Vannan in Aust Occup Ther J 55:212-214, 2008): a parent-assisted
      group-based treatment for sleep disturbance which was recently adapted for older
      children and adolescents with DD. Twenty-six families with children aged 8-17
      years participated. The study compared a treatment and a wait-list control group
      at baseline, post-treatment and 2 months post-treatment on measures of child and
      parent functioning. Results demonstrated that the Sleepwise approach was
      effective in reducing sleep disturbance and parent stress. Limitations and future
      research directions are discussed.

PMID- 24442796
TI  - Polymethylene-based copolymers by polyhomologation or by its combination with
      controlled/living and living polymerizations.
AB  - Polyhomologation, recently developed by Shea, is a borane-initiated living
      polymerization of ylides leading to linear polymethylenes (C1 polymerization)
      with controlled molecular weight, low polydispersity, and well-defined
      structures. In this Review, the copolyhomologation of different ylides as well as
      the combination of polyhomologation with controlled/living (nitroxide-mediated,
      atom transfer radical, reversible addition-fragmentation chain-transfer) and
      living (ring opening, anionic) polymerizations is discussed. 

PMID- 24442797
TI  - Three-dimensional brain MRI for DBS patients within ultra-low radiofrequency
      power limits.
AB  - BACKGROUND: For patients with deep brain stimulators (DBS), local absorbed
      radiofrequency (RF) power is unknown and is much higher than what the system
      estimates. We developed a comprehensive, high-quality brain magnetic resonance
      imaging (MRI) protocol for DBS patients utilizing three-dimensional (3D) magnetic
      resonance sequences at very low RF power. METHODS: Six patients with DBS were
      imaged (10 sessions) using a transmit/receive head coil at 1.5 Tesla with
      modified 3D sequences within ultra-low specific absorption rate (SAR) limits (0.1
      W/kg) using T2 , fast fluid-attenuated inversion recovery (FLAIR) and T1 
      weighted image contrast. Tissue signal and tissue contrast from the low-SAR
      images were subjectively and objectively compared with routine clinical images of
      six age-matched controls. RESULTS: Low-SAR images of DBS patients demonstrated
      tissue contrast comparable to high-SAR images and were of diagnostic quality
      except for slightly reduced signal. CONCLUSIONS: Although preliminary, we
      demonstrated diagnostic quality brain MRI with optimized, volumetric sequences in
      DBS patients within very conservative RF safety guidelines offering a greater
      safety margin.

PMID- 24442799
TI  - Quantitative photoswitching in bis(dithiazole)ethene enables modulation of light
      for encoding optical signals.
AB  - Using one ray of light to encode another ray of light is highly desirable because
      information in optical format can be directly transferred from one beam to
      another without converting back to the electronic format. One key medium to
      accomplish such an amazing task is photoswitchable molecules. Using
      bis(dithiazole)ethene that can be photoswitched between its ring-open and ring
      closed states quantitatively with excellent fatigue resistance and high thermal
      stability, it is shown that quantitative photoreversibility allowed the
      photoswitching light to control other light travelling through the
      photoswitchable medium, a phenomenon of transferring information encoded in one
      light ray to others, thus imparting photo-optical modulation on the orthogonal
      light beam. 

PMID- 24442800
TI  - Silicic-acid uptake in diatoms studied with [(68)Ge]germanic acid as tracer.
AB  - Uptake of silicic acid in the diatoms Navicula pelliculosa and Nitzschia alba was
      studied, using the natural isotope, (28)Si, or a radioisotope, (31)Si. The rate
      of uptake of silicic acid was also determined by using [(68)Ge]germanic acid as a
      tracer of silicic acid. At a given silicicacid concentration in the growth
      medium, the fractions of [(68)Ge]germanic acid taken up followed closely the
      fraction of silicic acid taken up in the same time period. When the initial
      concentration of silicic acid was varied at a constant (trace) concentration of
      [(68)Ge]-germanic acid, the uptake of (68)Ge followed the fraction of silicic
      acid removed, and not the absolute amount removed from the medium, at all silicic
      acid concentrations. The usefulness of this approach in studying silicic-acid
      uptake is discussed. 

PMID- 24442798
TI  - The impact of inhibition capacities and age on number-space associations.
AB  - Numerical and spatial representations are tightly linked, i.e., when doing a
      binary classification judgment on Arabic digits, participants are faster to
      respond with their left/right hand to small/large numbers, respectively (Spatial
      Numerical Association of Response Codes, SNARC effect, Dehaene et al. in J Exp
      Psychol Gen 122:371-396, 1993). To understand the underlying mechanisms of the
      well-established SNARC effect, it seems essential to explore the considerable
      inter-individual variability characterizing it. The present study assesses the
      respective roles of inhibition, age, working memory (WM) and response speed.
      Whereas these non-numerical factors have been proposed as potentially important
      factors to explain individual differences in SNARC effects, none (except response
      speed) has so far been explored directly. Confirming our hypotheses, the results
      show that the SNARC effect was stronger in participants that had weaker
      inhibition abilities (as assessed by the Stroop task), were relatively older and
      had longer response times. Interestingly, whereas a significant part of the age
      influence was mediated by cognitive inhibition, age also directly impacted the
      SNARC effect. Similarly, cognitive inhibition abilities explained inter
      individual variability in number-space associations over and above the factors
      age, WM capacity and response speed. Taken together our results provide new
      insights into the nature of number-space associations by describing how these are
      influenced by the non-numerical factors age and inhibition. 

PMID- 24442801
TI  - Purification, stabilization and characterization of nitrite reductase from barley
      roots.
AB  - Nitrite reductase (NiR) isolated from barley (Hordeum vulgare L.) roots was
      stabilized in a buffer solution containing a sulfhydryl-reducing reagent and
      glycerol. The enzyme was purified 340fold by ammonium sulfate fractionation and
      chromatography on DEAE-Sephadex A-50, Sephadex G-200 and DEAE-cellulose. Purified
      NiR had a specific activity of 28 MUmol NO2 (-) reduced min(-1) mg(-1) of
      protein. The purified preparation was reddishbrown having absorption maxima at
      282, 388 and 577 nm. The barley-root enzyme was almost identical with spinach
      leaf NiR with respect to molecular weight, isoelectric point, pH stability, pH
      optimum, affinity for substrate, behavior toward inhibitors. It is concluded that
      NiR is the same enzymatic entity regardless of its localization in photosynthetic
      or nonchlorophyllous tissues. The electron-transport system for NiR in root
      tissue is discussed in comparison with that in leaf tissue. 

PMID- 24442802
TI  - [Influence of NaCl- and abscisic acid treatment on protein metabolism and some
      further enzymes of amino acid metabolism in seedlings of Pennisetum typhoides].
AB  - The effects of sodium chloride (NaCl) and abscisic acid (ABA) on protein
      synthesis, protein hydrolysis, glutamine synthetase, Delta-pyrroline-5
      carboxylate reductase and amino acid composition have been studied in aerial
      parts of Pennisetum typhoides (Stapf et Hubbard) seedlings. Whereas protein
      synthesis is inhibited by NaCl and ABA, the activity or the synthesis of leucine
      arylamidase, glutamine synthetase and Delta-pyrroline-5-carboxylate reductase is
      promoted by both the substances. The results of the amino acid analysis showed
      that in the presence of NaCl and ABA the amounts of alanine, aspartate and
      ammonia decreased, while the concentrations of glutamate, and especially that of
      proline increased greatly. The possible significance of the results in explaining
      the proline accumulation under stress conditions and ABA-treatment is discussed. 

PMID- 24442803
TI  - IAA transport during the phototropic responses of intact Zea and Avena
      coleoptiles.
AB  - Transport of indolyl-3-acetic acid (IAA) was studied during the phototropic
      responses of intact shoots and detached coleoptiles of Zea mays L. and Avena
      sativa L. The use of a high specific activity [5-(3)H]IAA and glass micropipettes
      enabled asymmetric application of the IAA to be made to individual coleoptiles
      with minimal tissue damage.A unilateral stimulus of 2.59*10(-11) einstein cm(-2)
      of blue light, probably in the dose range of the first positive phototropic
      response, caused significant net lateral movement of radioactivity from [5
      (3)H]IAA away from the illuminated side of intact shoots and detached coleoptile
      apices of both Avena and Zea. The magnitude of the net lateral movement was 15.3%
      in Zea seedlings and 12.3% in Avena seedlings. Chromatographic analyses indicated
      that the movement of radioactivity reflected that of IAA. A phototropic stimulus
      of 1.24*10(-7) einstein cm(-2), which was probably in the second positive dose
      range, caused significant lateral movement of radioactivity in intact shoots and
      detached coleoptiles of Zea but not of Avena.In intact Zea seedlings, neither
      phototropic dosage affected the longitudinal transport of IAA. In intact Avena
      seedlings, first positive stimulation inhibited longitudinal transport only when
      the IAA was applied to the illuminated side of the coleoptile, but second
      positive stimulation inhibited basipetal movement of IAA regardless of the side
      of application.Exposing the intact seedlings to red light before phototropic
      stimulation abolished lateral transport after a first positive stimulus in Zea
      and in Avena.Phototropic stimulation can thus induce a lateral transport of IAA
      towards the shaded side of the coleoptiles of both Zea and Avena seedlings, and
      can affect longitudinal movement of IAA in the coleoptile of Avena. However,
      since phototropic curvature was observed under certain conditions in the absence
      of either of these effects, the extent to which they are involved in the
      induction of asymmetric growth in a stimulated coleoptile has yet to be resolved.

PMID- 24442804
TI  - Apical dominance in roots of Pisum sativum L.
AB  - The influence of several natural and synthetic hormones on apical dominance of
      pea roots was investigated. Extracts of roots decapitated just before extraction
      or 12 h earlier were compared in a lateral root formation assay, in the
      Amaranthus assay for cytokinins and the Avena coleoptile assay. Indole-3-acetic
      acid shows a strong promotive effect on the initiation of lateral roots.
      Gibberellic acid has no significant effect. Abscisic acid and its presumable
      precursor xanthoxin show a strong inhibitory effect, and so do all cytokinins
      investigated (kinetin, benzyladenine, and zeatin). Decapitation of roots caused a
      significant increase in the number of lateral root primordia within 12 h. Paper
      chromatograms of root extracts indicate the presence of at least two inhibitors
      of lateral root formation in the alkaline fraction, and of two promoters in the
      acid fraction. The amount of both inhibitors seems to decrease if the tip of the
      main root is removed 12 h before extraction whereas the promoters of lateral root
      formation do not change in their concentration. The Amaranthus test shows
      cytokinin activity in the region of one of the two inhibitors, and this activity
      decreases after decapitation. The second inhibitor has the Rf of xanthoxin; it
      inhibits the growth of Avena coleoptiles and its activity also decreases after
      decapitation. 

PMID- 24442805
TI  - The activity of abscisic acid analogues as inhibitors of stomatal opening.
AB  - Ten analogues of abscisic acid (ABA) have been tested for their activity in
      assays based on the induction of stomatal closing on isolated epidermis of
      Commelina communis L., and the inhibition of opening on intact leaves of Xanthium
      strumarium L. Three of the analogues showed activity comparable to that of ABA on
      the stomata of Commelina. The same analogues also showed similar activity and
      persistence as ABA when applied to the leaf surfaces of Xanthium. Molecular
      requirements for activity on stomata agree closely with those for activity in the
      Avena coleoptile assay. The possible value of the analogues as antitranspirants
      is considered. 

PMID- 24442806
TI  - Changes in plastid envelope polypeptides during chloroplast development.
AB  - A quantitative estimation of sodium dodecyl sulphate-extractable plastid envelope
      polypeptides during greening of Avena sativa L. laminae is described, combined
      with protein distribution and plastid number studies over the same period.A
      primary light-dependent and cytoplasm-dependent increase in both total plastid
      protein and envelope associated protein during the first 30 minutes of greening
      was observed, followed by a period during which release of envelope-associated
      protein either into the plastid or into the cytoplasm, or both, takes place.
      After 8 hours greening an increase in plastid envelope protein reflects a
      requirement for an increased plastid surface area during chloroplast maturation.A
      comparison of the behaviour of envelope membranes during illuminated in vitro
      incubation of isolated etio-plasts with plastids isolated from tissue given
      similar illumination pre-treatments, indicates that the early increase in
      envelope-associated protein is real and requires the participation of the
      cytoplasm. 

PMID- 24442807
TI  - [Influence of light and medium on the plating efficiency of isolated cells from
      callus cultures of Nicotiana tabacum var. "Samsun"].
AB  - Light increases the plating efficiency of single cells isolated from green callus
      cultures of Nicotiana tabacum var. "Samsun" and plated in densities of less than
      100 cells ml(-1) by more than 100%. At optimal light intensities plating
      efficiences between 80 and 90% were achieved with green cells, whereas the growth
      of isolated cells from chlorophyll free callus cultures was inhibited by
      light.Plated at low densities the isolated tobacco cells require the addition of
      kinetin and glutamine to a modified Murashige-Skoog-Medium for growth. The
      addition of these two substances is not necessary in the case of callus cultures
      or at higher plating densities (i.e. 500 or more cells ml(-1)). The requirement
      of kinetin for the growth of isolated cells can be met by the addition of small
      amounts of conditioned media from suspension cultures to the modified M+S-medium
      supplemented with glutamine, which demonstrates the production and release of a
      highly active cytokinine by the cells. 

PMID- 24442808
TI  - [Stomatal opening in the dark at high temperatures].
AB  - Transpiration and absorption of water by the roots of Piper betle L. have been
      measured simultaneously with intact single-leaf plants. The degree of stomatal
      opening has been calculated from leaf temperature, air humidity and wind speed.
      The roots were aerated at intervals.In an atmosphere of unchanged composition,
      the stomata of Piper betle L. remain closed or only slightly open at a leaf
      temperature of 36-38 degrees  C in the dark and at night. However, if the
      temperature is raised above 40 degrees  C, they open rapidly after a short time
      lag to a degree normally met only under daylight conditions.Opening occurs
      independently of the length of the preceding dark period and hour of the night.
      The high degree of opening in the dark does not change considerably for many
      hours, and is more pronounced at high air humidity. At temperatures above 40
      degrees  C the degree of opening is little influenced by the change from light to
      dark or from dark to light.The results give evidence that heat resistance could
      be strongly affected by stomatal reactions at high temperatures. The maximum
      temperature during the experiments did not exceed 45 degrees  C. To ensure that
      Piper betle L. had not been damaged by the high temperature the experiments were
      repeated with the same plants on several consecutive days, and the same results
      were obtained.Close agreement was found between the highest possible stomatal
      conductance derived from transpiration and that calculated from scanning electron
      microscopic analysis. 

PMID- 24442809
TI  - Lateral movement of radioactivity from [(14)C]gibberellic acid (GA 3) in roots
      and coleoptiles of Zea mays L. seedlings during geotropic stimulation.
AB  - An upward lateral movement of radioactivity from [(14)C]gibberellic acid (GA3)
      has been found to occur in geotropically stimulated coleoptiles and primary roots
      of intact Zea mays (L.) seedlings. 

PMID- 24442810
TI  - A psychiatric curriculum directed to the care of the Hispanic patient.
AB  - Hispanics are the second-largest ethnic minority group in the United States,
      numbering approximately 20.7 million. This population has distinct cultural and
      linguistic characteristics with which psychiatrists should be familiar, and
      psychiatric residents should be taught how to appropriately diagnose and treat
      Hispanic patients. This article describes a model curriculum for psychiatric
      residency training programs that addresses the sociodemographic, epidemiological,
      psychosocial, cultural, and behavioral characteristics of Hispanics. The authors
      strongly recommend that faculty who are knowledgeable and sensitive about
      Hispanic culture be available for the supervision and teaching of psychiatric
      residents during their training. Supervision should focus on key educational
      issues such as cultural formulation, family dynamics, and other factors of
      importance in clinical psychiatric practice. A bibliography of relevant works is
      also included. 

PMID- 24442811
TI  - Malpractice and the psychiatrist : a primer for residents.
AB  - Over the past two decades, the number of malpractice claims filed against
      psychiatrists has risen steadily, so that about 6% of all psychiatrists are named
      in new lawsuits each year. Psychiatrists-in-training are just as susceptible to
      lawsuits as their board-certified colleagues, and psychiatric residents work in
      settings where the likelihood of events that generate litigation is high. This
      primer introduces residents to the major issues involved in psychiatric
      malpractice. The article also discusses aspects of clinical practice that are
      especially affected by potential malpractice liability and outlines practical
      methods for limiting vulnerability to adverse malpractice litigation. 

PMID- 24442812
TI  - Redefining the role of family therapy in psychiatric residency education.
AB  - In order to learn how psychiatry residents use family therapy training from
      residency in their clinical practices after graduation, the authors interviewed
      graduates from a large program in the metropolitan Northeast and a small program
      in the rural South. Graduates from both programs were using family therapy theory
      and skills to a greater extent than they had anticipated during residency.
      However, these skills were being used primarily to treat individual patients and
      to solve clinical and administrative problems in settings other than traditional
      couple and family therapies. Based on the findings, the authors suggest a
      restructuring of content and redefinition of role for family therapy training in
      psychiatry residencies. 

PMID- 24442813
TI  - The Stress Management Workshop for Medical Students : Realizing Psychiatry's
      Potential.
AB  - Stress management workshops have been used in psychiatric training programs, both
      the medical student and resident levels. However, their use has been sparingly
      described. A workshop of this nature was adapted for use with medical students at
      the University of Illinois and presented as an elective in 1994 and 1995.
      Seventeen percent of the students in each class of 180 chose this elective.
      Questionnaire results indicated that the course was well received and that the
      students selecting the course were predominantly attracted to the "non
      procedural" specialties. Almost half the students indicated that the course had
      made them consider a career in psychiatry and that their attitude toward
      psychiatry had become more positive. Every student taking the course stated that
      it should be repeated and was helpful in their own personal stress management.
      The stress management workshop may be a useful and needed adjunct to medical
      school training. 

PMID- 24442814
TI  - Sesquicentennial anniversary of academic psychiatry.

PMID- 24442816
TI  - The world wide web : new horizons.

PMID- 24442817
TI  - Dexmedetomidine for the management of awake fibreoptic intubation.
AB  - BACKGROUND: Awake fibreoptic intubation (AFOI) frequently requires sedation,
      anxiolysis and relief of discomfort without impairing ventilation and depressing
      cardiovascular function. The goal is to allow the patient to be responsive and co
      operative. Medications such as fentanyl, remifentanil, midazolam and propofol
      have been reported to assist AFOI; however,these agents are associated with
      cardiovascular or respiratory adverse effects. Dexmedetomidine has been proposed
      as an alternative to facilitate AFOI. OBJECTIVES: The primary objective of this
      review is to evaluate and compare the efficacy and safety of dexmedetomidine in
      the management of patients with a difficult or unstable airway undergoing awake
      fibreoptic intubation (AFOI). SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL; 2012, Issue 5), MEDLINE (1966 to May
      2012) through Ovid, EMBASE (1980 to May 2012) and Web of Science (1945 to May
      2012); we screened the reference lists of all eligible trials and reviews to look
      for further trials and contacted authors of trials to ask for additional
      information. We searched for ongoing trials at http://www.controlledtrials.com/
      and http://clinicaltrials.gov/ . We reran our search of all databases listed
      above on 21 November 2013. SELECTION CRITERIA: We included published and
      unpublished randomized controlled trials, regardless of blinding or language of
      publication, in participants 18 years of age or older who were scheduled for an
      elective AFOI because of an anticipated difficult airway. Participants received
      dexmedetomidine or control medications. DATA COLLECTION AND ANALYSIS: Three
      review authors independently extracted data on study design, participants,
      interventions and outcomes. We assessed risk of bias using The Cochrane
      Collaboration's tool. We estimated risk ratios (RRs) or mean differences (MDs)
      with 95% confidence internals (CIs) for outcomes with sufficient data; for other
      outcomes, we performed a qualitative analysis. MAIN RESULTS: We identified four
      randomized controlled trials (RCTs), which included 211 participants. The four
      trials compared dexmedetomidine with midazolam, fentanyl, propofol or a sodium
      chloride placebo, respectively. The trials showed low or unclear risk of bias
      primarily because information provided on allocation concealment and other
      potential sources of bias was inadequate. Owing to clinical heterogeneity and
      potential methodological heterogeneity, it was impossible to conduct a full meta
      analysis. We described findings from individual studies or presented them in
      tabular form. Limited evidence was available for assessment of the outcomes of
      interest for this review. Results of the limited included trials showed that
      dexmedetomidine significantly reduced participants' discomfort with no
      significant differences in airway obstruction, low oxygen levels or treatment
      emergent cardiovascular adverse events noted during AFOI compared with control
      groups. When the search was rerun (from May 2012 to November 2013), it was noted
      that four studies are awaiting assessment. We will deal with these studies when
      we update the review. AUTHORS' CONCLUSIONS: Small, limited trials provide weak
      evidence to support dexmedetomidine as an option for patients with an anticipated
      difficult airway who undergo AFOI. The findings of this review should be further
      corroborated by additional controlled investigations.

PMID- 24442818
TI  - Endophytic fungi associated with Macrosolen tricolor and its host Camellia
      oleifera.
AB  - Endophytic fungi play an important role in terrestrial ecosystem, while little is
      known about those in hemi-parasitic plants, a group of special plants which
      absorb nutrients from its hosts by haustoria. The relationship of the endophytes
      in the two parts of the bipartite systems (hemiparasites together with their
      hosts) is also poorly understood. Endophytic fungi of a hemi-parasitic plant
      Macrosolen tricolor, and its host plant Camellia oleifera were investigated and
      compared in this study. M. tricolor contained rich and diversified endophytic
      fungi (H' = 2.829), which consisted mainly of ascomycetes, distributed in more
      than ten orders of four classes (Sordariomycetes, Dothideomycetes, Leotiomycetes
      and Eurotiomycetes) besides Incertae sedis strains (23.2 % of total). In
      addition, 2.2 % of isolates were identified to be Basidiomycota, all of which
      belonged to Agaricomycetes. Obvious differences were observed between the
      endophytic fungal assembles in the leaves and those in the branches of M.
      tricolor. The endophytic fungi isolated from C. oleifera distributed in nearly
      same orders of the four classes of Ascomycota and one class (Agaricomycetes) of
      Basidiomycota as those from M. tricolor with similar proportion. For both M.
      tricolor and C. oleifera, Valsa sp. was the dominant endophyte species in the
      leaves, Torula sp. 1 and Fusarium sp. 1 were the dominant endophytic fungi in the
      branches. The similarity coefficient of the endophyte assembles in the two host
      was 64.4 %. Canonical correspondence analysis showed that the endophyte assembles
      of M. tricolor and C. oleifera were significantly different (p < 0.01). 

PMID- 24442819
TI  - Diversity of culturable yeasts in phylloplane of sugarcane in Thailand and their
      capability to produce indole-3-acetic acid.
AB  - Yeasts were isolated by the enrichment technique from the phylloplane of 94
      samples of sugarcane leaf collected from seven provinces in Thailand. All
      sugarcane leaf samples contained yeasts and 158 yeast strains were obtained. On
      the basis of the D1/D2 domain of the large subunit rRNA gene sequence analysis,
      144 strains were identified to 24 known species in 14 genera belonging to the
      Ascomycota viz. Candida akabanensis, Candida dendronema, Candida mesorugosa,
      Candida michaelii, Candida nivariensis, Candida rugosa, Candida orthopsilosis,
      Candida quercitrusa, Candida tropicalis, Candida xylopsoci, Cyberlindnera
      fabianii, Cyberlindnera rhodanensis, Debaryomyces nepalensis, Hannaella aff.
      coprosmaensis, Hanseniaspora guilliermondii, Kluyveromyces marxianus, Lachancea
      thermotolerans, Lodderomyces elongisporus, Metschnikowia koreensis, Meyerozyma
      caribbica, Millerozyma koratensis, Pichia kudriavzevii, Torulaspora delbrueckii
      and Wickerhamomyces edaphicus, and 12 species in six genera of the Basidiomycota
      viz . Cryptococcus flavescens, Cryptococcus laurentii, Cryptococcus
      rajasthanensis, Kwoniella heveanensis, Rhodosporidium fluviale, Rhodosporidium
      paludigenum, Rhodotorula mucilaginosa, Rhodotorula sesimbrana, Rhodotorula
      taiwanensis, Sporidiobolus ruineniae, Sporobolomyces carnicolor and
      Sporobolomyces nylandii. Seven strains were identical or similar to four
      undescribed species. Another seven strains represented four novels species in the
      genus Metschnikowia, Nakazawaea, Wickerhamomyces and Yamadazyma. The results
      revealed 69 % of the isolated strains were ascomycete yeasts and 31 % were
      basidiomycete yeast. The most prevalent species was M. caribbica with a 23 %
      frequency of occurrence followed by Rh. taiwanensis (11 %) and C. tropicalis (10
      %). All strains were assessed for indole-3-acetic acid (IAA) producing capability
      showing that 69 strains had the capability of producing IAA when cultivated in
      yeast extract peptone dextrose broth supplemented with 1 g/L L-tryptophan. The
      highest IAA concentration of 565.1 mg/L was produced by R. fluviale DMKU-RK253. 

PMID- 24442820
TI  - Influence of climate factors on Vibrio cholerae dynamics in the Pearl River
      estuary, South China.
AB  - Current research has seldom focused on the quantitative relationships between
      Vibrio cholerae (V. cholerae) and climate factors owing to the complexities and
      high cost of field observation in the aquatic environment. This study has focused
      on the relationships between V. cholerae and climate factors based on linear
      regression method and data partition method. Data gathered from 2008 to 2009 in
      the Pearl River estuary, South China, were adopted. Positive rate of V. cholerae
      was correlated closely with monthly climate factors of water temperature and air
      temperature, respectively in 2009. Quarterly data analysis from 2008 to 2009
      showed that there existed seasonal characteristic for V. cholerae. Positive rate
      of V. cholerae was correlated positively with quarterly climate factors of land
      surface temperature, pH, water temperature, air temperature and rainfall,
      respectively and negatively with quarterly air pressure. Partition data analysis
      in 2009 showed that there existed geography region characteristic for V.
      cholerae. V. cholerae dynamics was closely correlated to climate factors in the
      downstream area. However, it was more greatly affected by human geography factors
      in the urban area. Positive annual rate of V. cholerae was higher in the
      downstream area than in the urban area both in 2008 and 2009. At last, a cellular
      automaton model was used to simulate V. cholerae diffusion downstream, and the
      distribution of V. cholerae obtained from this model was similar to that obtained
      from the field observations. 

PMID- 24442821
TI  - The effects of different crossing-linking conditions of genipin on type I
      collagen scaffolds: an in vitro evaluation.
AB  - The purpose of this paper is to analyze the properties of fabricating rat tail
      type I collagen scaffolds cross-linked with genipin under different conditions.
      The porous genipin cross-linked scaffolds are obtained through a two step freeze
      drying process. To find out the optimal cross-link condition, we used different
      genipin concentrations and various cross-linked temperatures to prepare the
      scaffolds in this study. The morphologies of the scaffolds were characterized by
      scanning electron microscope, and the mechanical properties of the scaffolds were
      evaluated under dynamic compression. Additionally, the cross-linking degree was
      assessed by ninhydrin assay. To investigate the swelling ratio and the in vitro
      degradation of the collagen scaffold, the tests were also carried out by
      immersion of the scaffolds in a PBS solution or digestion in a type I collagenase
      respectively. The morphologies of the non-cross-linked scaffolds presented a
      lattice-like structure while the cross-linked ones displayed a sheet-like
      framework. The morphology of the genipin cross-linked scaffolds could be
      significantly changed by either increasing genipin concentration or the
      temperature. The swelling ratio of each cross-linked scaffold was much lower than
      that of the control (non-cross-linked).The ninhydrin assay demonstrated that the
      higher temperature and genipin concentration could obviously increase the cross
      linking efficiency. The in vitro degradation studies indicated that genipin cross
      linking can effectively elevate the biostability of the scaffolds. The
      biocompatibility and cytotoxicity of the scaffolds was evaluated by culturing rat
      chondrocytes on the scaffold in vitro and by MTT. The results of MTT and the fact
      that the chondrocytes adhered well to the scaffolds demonstrated that genipin
      cross-linked scaffolds possessed an excellent biocompatibility and low
      cytotoxicity. Based on these results, 0.3 % genipin concentrations and 37 
      degrees C cross-linked temperatures are recommended. 

PMID- 24442822
TI  - Macrophage-mediated injury and repair after ischemic kidney injury.
AB  - Acute ischemic kidney injury is a common complication in hospitalized patients.
      No treatment is yet available for augmenting kidney repair or preventing
      progressive kidney fibrosis. Animal models of acute kidney injury demonstrate
      that activation of the innate immune system plays a major role in the systemic
      response to ischemia/reperfusion injury. Macrophage depletion studies suggest
      that macrophages, key participants in the innate immune response, augment the
      initial injury after reperfusion but also promote tubular repair and contribute
      to long-term kidney fibrosis after ischemic injury. The distinct functional
      outcomes seen following macrophage depletion at different time points after
      ischemia/reperfusion injury suggest heterogeneity in macrophage activation
      states. Identifying the pathways that regulate the transitions of macrophage
      activation is thus critical for understanding the mechanisms that govern both
      macrophage-mediated injury and repair in the postischemic kidney. This review
      examines our understanding of the complex and intricately controlled pathways
      that determine monocyte recruitment, macrophage activation, and macrophage
      effector functions after renal ischemia/reperfusion injury. Careful delineation
      of repair and resolution pathways could provide therapeutic targets for the
      development of effective treatments to offer patients with acute kidney injury. 

PMID- 24442825
TI  - Commentary.

PMID- 24442824
TI  - Genetic basis of familial isolated hyperparathyroidism: a case series and a
      narrative review of the literature.
AB  - Primary hyperparathyroidism is a heterogeneous clinical entity. In the clinical
      setting, the diagnosis and management of familial isolated hyperparathyroidism
      (FIHP) and other familial hyperparathyroidism (FHPT) forms continue to rely on
      clinical, laboratory, and histological findings, with careful examination of the
      family. In this article, we report a case series of FIHP in a four-generation
      Greek family, with no identifiable gene mutations. Clinical approach and long
      term follow-up are discussed and a narrative review of the genetic basis of this
      entity has been performed. 

PMID- 24442827
TI  - The mechanism of photosynthetic water oxidation.
AB  - Photosynthetie water oxidation is unique to plants and cyanobacteria, it occurs
      in thylakoid membranes. The components associated with this process include: a
      reaction center polypeptide, having a molecular weight (Mr) of 47-50 kilodaltons
      (kDa), containing a reaction center chlorophyll a labeled as P680, a
      plastoquinol(?)-electron donor Z, a primary electron acceptor pheophytin, and a
      quinone electron acceptor QA; three 'extrinsic' polypeptides having Mr of
      approximately 17 kDa, 23 kDa, and 33 kDa; and, in all likelihood, an
      approximately 34 kDa 'intrinsic' polypeptide associated with manganese (Mn)
      atoms. In addition, chloride and calcium ions appear to be essential components
      for water oxidation. Photons, absorbed by the so-called photosystem II, provide
      the necessary energy for the chemical oxidation-reduction at P680; the oxidized
      P680 (P680(+)), then, oxidizes Z, which then oxidizes the water-manganese system
      contained, perhaps, in a protein matrix. The oxidation of water, leading to O2
      evolution and H(+) release, requires four such independent acts, i.e., there is a
      charge accumulating device (the so-called S-states). In this minireview, we have
      presented our current understanding of the reaction center P680, the chemical
      nature of Z, a possible working model for water oxidation, and the possible roles
      of manganese atoms, chloride ions, and the various polypeptides, mentioned above.
      A comparison with cytochrome c oxidase, which is involved in the opposite process
      of the reduction of O2 to H2O, is stressed.This minireview is a prelude to the
      several minireviews, scheduled to be published in the forthcoming issues of
      Photosynthesis Research, including those on photosystem II (by H.J. van Gorkom);
      polypeptides of the O2-evolving system (by D.F. Ghanotakis and C.F. Yocum); and
      the role of chloride in O2 evolution (by S. Izawa). 

PMID- 24442828
TI  - Transverse heterogeneity in lipid fluidity in spinach thylakoids, photosystem II
      preparations, and thylakoid galactolipid vesicles.
AB  - We have used three doxyl stearic acid spin labels to study the transverse hetero
      geneity in lipid fluidity in thylakoids, photosystem II (PS II) preparations, and
      thylakoid galactolipid vesicles. This comparative study shows that spin labels
      incorporated into the membrane of the PS II preparation experience far more
      immobilization than do the same spin labels incorporated into either thylakoids
      or vesicles prepared from the polar lipids extracted from thylakoids. The spin
      label immobilization found in the PS II preparation is manifest even near the
      center of the bilayer, where lipid mobility is normally at its maximum. Analysis
      of the lipid content of the PS II preparation, relative to chlorophyll, suggests
      that the PS II preparation may be lipid depleted. This lipid depletion could
      explain the results presented. However, electron microscopy [Dunahay et al.
      (1984) Biochim. Biophys. Acta 764:179-193] has not indicated that major
      delipidation has occurred, and so it remains possible that the immobilization
      found in the PS II preparation is due primarily to the normal (but close)
      juxtaposition of adjacent PS II complexes and the cooperative immobilization of
      their surrounding lipids. Based on the results presented, we conclude that highly
      mobile lipids are not required for oxygen evolution, the primary photochemistry
      or the secondary reduction of exogenously added quinones. Unfortunately, the
      relationship between the plastoquinone pool and the fluidity of the membrane in
      the PS II preparation remains ambiguous. 

PMID- 24442829
TI  - Chlorophyll fluorescence at 77 K in intact leaves: Characterization of a
      technique to eliminate artifacts related to self-absorption.
AB  - Due to the optical density of photosynthetic tissues the spectral characteristics
      of fluorescence emitted at 77 K directly from frozen plant material are distorted
      by differential re-absorption of the emitted light: the emission band related to
      PSII can be lowered by more than 80%, relative to the PSI band and the profile of
      the excitation spectra becomes flattened. It is demonstrated that such distortion
      cannot be neglected as its extent varies from sample to sample. A technique is
      introduced to eliminate sample artifacts related to self-absorption: subcellular
      small particles are prepared from rapidly cooled leaves and then 'diluted'
      without re-thawing at a concentration corresponding to about 5 MUg
      chlorophyll.cm(-3) into a matrix consisting of ice and quartz particles. The
      photochemical pigment apparatus is expected to remain fixed in the in vivo state.
      Different kinds of plant material is used and it is demonstrated how this
      preparative approach allows to study the in vivo distribution of energy between
      the two photosystems from pure 77 K spectrofluorimetry, even when the optical
      properties of whole leaves or thalli normally would exclude quantitative
      analysis. 

PMID- 24442826
TI  - Photosynthetic ATPases: purification, properties, subunit isolation and function.
AB  - Photosynthetic coupling factor ATPases (F1-ATPases) generally censist of five
      subunits named alpha, beta, gamma, delta and epsilon in order of decreasing
      apparent molecular weight. The isolated enzyme has a molecular weight of between
      390,000 to 400,000, with the five subunits probably occurring in a 3:3:1:1:1
      ratio. Some photosynthetic F1 ATPases are inactive as isolated and require
      treatment with protease, heat or detergent in order to elicit ATPase activity.
      This activity is sensitive to inhibition by free divalent cations and appears to
      be more specific for Ca(2+) vs. Mg(2+) as the metal ion substrate chelate. This
      preference for Ca(2+) can be explained by the higher inhibition constant for
      inhibition of ATPase activity by free Ca(2+). Methods for the assay of a Mg
      dependent ATPase activity have recently been described. These depend on the
      presence of organic solvents or detergents in the reaction mixture for assay. The
      molecular mechanism behind the expression of either the Ca- or Mg-ATPase
      activities is unknown. F1-ATPases function to couple proton efflux from thylakoid
      membranes or chromatophores to ATP synthesis. The isolated enzyme may thus also
      be assayed for the reconstitution of 'coupling activity' to membranes depleted of
      coupling factor 1.The functions of the five subunits in the complex have been
      deduced from the results of chemical modification and reconstitution studies. The
      delta subunit is required for the functional binding of the F1 to the F0. The
      active site is probably contained in the beta (and alpha) subunit(s). The
      proposed functions for the gamma and epsilon subunits are, however, still matters
      of controversy. Coupling factors from a wide variety of species including
      bacteria, algae, C3 and C4 plants, appear to be immunologically related. The beta
      subunits are the most strongly related, although the alpha and gamma subunits
      also show significant immunological cross-reactivity. DNA sequence analyses of
      the genes for the beta subunit of CF1 have indicated that the primary sequence of
      this polypeptide is highly conserved. The genes for the polypeptides of CF1
      appear to be located in two cellular compartments. The alpha, beta and epsilon
      subunits are coded for on chloroplast DNA, whereas the gamma and delta subunits
      are probably nuclear encoded. Experiments involving protein synthesis by isolated
      chloroplasts or protein synthesis in the presence of inhibitors specific for one
      or the other set of ribosomes in the cell suggest the existence of pools of
      unassembled CF1 subunits. These pools, if they do exist in vivo, probably make up
      no greater than 1% of the total CF1 content of the cell. 

PMID- 24442830
TI  - Growth, photosynthesis and photorespiration of Lemna gibba: response to
      variations in CO2 and O 2 concentrations and photon flux density.
AB  - Dry weight and Relative Growth Rate of Lemna gibba were significantly increased
      by CO2 enrichment up to 6000 MUl CO2 l(-1). This high CO2 optimum for growth is
      probably due to the presence of nonfunctional stomata. The response to high CO2
      was less or absent following four days growth in 2% O2. The Leaf Area Ratio
      decreased in response to CO2 enrichment as a result of an increase in dry weight
      per frond. Photosynthetic rate was increased by CO2 enrichment up to 1500 MUl CO2
      l(-1) during measurement, showing only small increases with further CO2
      enrichment up to 5000 MUl CO2 l(-1) at a photon flux density of 210 MUmol m(-2)
      s(-1) and small decreases at 2000 MUmol m(-1) s(-1). The actual rate of
      photosynthesis of those plants cultivated at high CO2 levels, however, was less
      than the air grown plants. The response of photosynthesis to O2 indicated that
      the enhancement of growth and photosynthesis by CO2 enrichment was a result of
      decreased photorespiration. Plants cultivated in low O2 produced abnormal
      morphological features and after a short time showed a reduction in growth. 

PMID- 24442831
TI  - The authors' reply to Koeser and McCrone: "on the use and interpretation of
      quantile regression in quality-of-life research".

PMID- 24442832
TI  - Modelling the cost effectiveness of rituximab in chronic lymphocytic leukaemia in
      first-line therapy and following relapse.
AB  - BACKGROUND: The efficacy and safety of adding rituximab to fludarabine and
      cyclophosphamide (R-FC) for the treatment of chronic lymphocytic leukaemia (CLL)
      has been demonstrated in two randomised trials: CLL-8 was conducted in previously
      untreated patients, and REACH was conducted in previously treated patients. In
      both trials, progression-free survival was increased in the R-FC treatment groups
      compared with the FC treatment groups. In CLL-8, overall survival was also
      significantly increased. OBJECTIVE: To develop an economic model to assess the
      cost effectiveness, from the Australian healthcare perspective, of rituximab when
      used as a treatment for both previously untreated and relapsed/refractory CLL.
      METHODS: A Markov model with three health states (unprogressed, progressed and
      death) was developed to extrapolate the trial results over a 15-year time
      horizon. A treatment algorithm was developed with Australian haematologists to
      inform the treatments to be modelled. The base-case compares up to three courses
      of six cycles of R-FC ('first-line' treatment) followed by three courses of post
      progression salvage ('Salvage') treatment (including rituximab) with three
      courses of FC followed by three courses of Salvage treatment (excluding
      rituximab). Subsequent treatments are incorporated into the model by repeating
      the unprogressed and progressed health states for each treatment. Time-dependent
      transition probabilities for the model were estimated from an analysis of
      individual patient data from CLL-8 and REACH. Comparisons of the hazard rates for
      the CLL-8 and REACH trials enabled an assessment of the impact on the transitions
      of receiving the same regimen as the first or second treatment, and hence inform
      assumptions regarding transitions for third and subsequent treatments. Costs
      applied in the model were based on published Australian prices in 2009. RESULTS:
      The model predicts patients receive an average of approximately two courses of
      treatment, and the addition of rituximab results in an incremental gain of 0.94
      quality-adjusted life-years (QALYs). The incremental cost associated with the
      addition of rituximab is A$40,268, and hence the cost per QALY gained (QALYG) is
      A$42,906. CONCLUSION: Rituximab, in combination with chemotherapy, when used
      multiple times throughout the treatment algorithm, appears to be cost effective
      for CLL from the Australian healthcare perspective, with a cost/QALYG within the
      range generally accepted as providing value.

PMID- 24442834
TI  - Enzalutamide after docetaxel and abiraterone therapy in metastatic castration
      resistant prostate cancer.
AB  - INTRODUCTION: Enzalutamide is a novel antiandrogen which is approved for the
      treatment of metastatic, castration-resistant prostate cancer (mCRPC) after
      taxane-based chemotherapy. The efficacy of enzalutamide after the sequence
      docetaxel and abiraterone is not proven. METHODS: Thirty-five mCRPC patients in
      the German compassionate use program, who received enzalutamide after progression
      with taxane-based chemotherapy and abiraterone were prospectively evaluated. The
      endpoints of the study were overall survival, radiologic progression-free
      survival and safety. RESULTS: The median treatment duration on enzalutamide was
      2.8 months. The median overall survival was 7.5 months [95% confidence interval
      (CI) 4.7-10.3] while median progression-free survival assessed by imaging was 3.1
      months (95% CI 1.4-4.8). The most common toxicities of all grades were anemia and
      weight loss. CONCLUSION: Although the results are limited by a small patient
      number, the consecutive use of enzalutamide and abiraterone after taxane-based
      chemotherapy shows a modest clinical activity. Thus, sequence therapy alternating
      between chemotherapy and antihormonal drugs might be a more promising approach in
      mCRPC treatment.

PMID- 24442835
TI  - Effects of observing eye contact on gaze following in high-functioning autism.
AB  - Observing eye contact between others enhances the tendency to subsequently follow
      their gaze and has been suggested to function as a social signal that adds
      meaning to an upcoming action or event. The present study investigated effects of
      observed eye contact in high-functioning autism (HFA). Two faces on a screen
      either looked at or away from each other before providing congruent or
      incongruent gaze cues to one of two target locations. In contrast to control
      participants, HFA participants did not depict enhanced gaze following after
      observing eye contact. Individuals with autism, hence, do not seem to process
      observed mutual gaze as a social signal indicating the relevance of upcoming
      (gaze) behaviour. This may be based on the reduced tendency of individuals with
      HFA to engage in social gaze behavior themselves, and might underlie some of the
      characteristic deficiencies in social communicative behaviour in autism. 

PMID- 24442836
TI  - Global processing fosters donations toward charity appeals framed in an approach
      orientation.
AB  - People are often influenced by how persuasive appeals are framed. While decisions
      and preferences seem dependent on the effects of a fit between one's regulatory
      focus and the motivational orientation of a message, specific cognitive
      mechanisms involved are not yet clear. This study investigated how perceptual
      processing styles (global vs local) linked with the scope of attention (broad vs
      narrow) influence decisions depending on motivation-dependent framing (approach
      vs avoidance). We found that a global processing style fits approach-oriented
      message appeals and fosters monetary allocation toward charities framed in eager
      motivational terms. We discuss implications of the findings on processing styles
      in relation to affective versus deliberate modes of processing and the need to
      address in detail the role of attentional scope-dependent processing styles in
      decision making.

PMID- 24442837
TI  - Evaluation of intensity and pulse width of different moderators for designing a
      new diffractometer for protein crystals with large unit cells in J-PARC/MLF.
AB  - We plan to design a high-resolution biomacromolecule neutron time-of-flight
      diffractometer, which allows us to collect data from crystals with unit cells
      above 250 A, in the materials and life science experimental facility at the Japan
      Proton Accelerator Research Complex. This new diffractometer can be used for a
      detailed analysis of large proteins such as membrane proteins and supermolecular
      complex. A quantitative comparison of the intensity and pulse width of a
      decoupled moderator (DM) against a coupled moderator (CM) considering the pulse
      width time resolution indicated that the DM satisfies the criteria for our
      diffractometer rather than the CM. The results suggested that a characteristic
      feature of the DM, i.e., narrow pulse width with a short tail, is crucial for the
      separation of Bragg reflections from crystals with large unit cells. On the other
      hand, it should be noted that the weak signals from the DM are buried under the
      high-level background caused by the incoherent scattering of hydrogen atoms,
      especially, in the case of large unit cells. We propose a profile-fitting
      integration method combined with the energy loss functions and a background
      subtraction method achieved by employing the statistics-sensitive nonlinear
      iterative peak-clipping algorithm. 

PMID- 24442839
TI  - Reply to the letter to the editor: Art in science: orthopaedics through
      philatelic material.

PMID- 24442838
TI  - Lateral ankle stabilization after distal fibular resection using a novel
      approach: a surgical technique.
AB  - BACKGROUND: After tumor resection involving the distal fibula, the method for
      recreating stability of the lateral ankle remains controversial. Many
      reconstructive options exist, including allograft reconstruction and arthrodesis;
      however, each of these approaches has significant potential disadvantages.
      DESCRIPTION OF TECHNIQUE: The distal fibula is resected as necessary to obtain
      negative margins for local control of the neoplasm. Reconstruction of the lateral
      ankle ligamentous complex is performed using the peroneus brevis tendon to
      reestablish lateral and anterior stability of the tibiotalar joint. The peroneus
      brevis tendon is transected proximally at it myotendinous junction and then
      sutured to the calcaneofibular and anterior talofibular ligaments in sequence and
      then tenodesed to the lateral distal tibia with suture anchors and a staple.
      METHODS: We present three patients who underwent distal fibulectomy for tumors
      originating in the distal fibula. All patients who have undergone the
      reconstruction being described are included within this cohort study. The
      patients were assessed clinically and radiographically at a range of 14 months to
      9.5 years (average, 4.8 years) for functional recovery, return of range of
      motion, stability of the ankle, and imaging evidence of arthrosis and
      instability. RESULTS: There were no episodes of instability or early progression
      to arthrosis. In addition, all patients obtained excellent ankle stability and
      range of motion on examination, but two had complications. One sustained a
      traumatic fracture to the base of the fifth metatarsal that healed with
      nonsurgical treatment and another who underwent further fibular shortening and
      bursectomy at the tip of the residual fibula with complete relief of his
      symptoms. CONCLUSIONS: Reconstruction of the lateral ankle after distal fibular
      resection is possible using the peroneus brevis tenodesed to the distal tibia and
      sutured to the remnants of the calcaneofibular and anterior talofibular ligaments
      as described in this surgical technique. In this small group, we found that
      patients were able to return to normal daily activities without instability or
      progression to tibiotalar arthrosis at short term; however, longer followup and
      larger series of patients are called for to confirm these findings.

PMID- 24442840
TI  - Let's talk about sex, baby: gendered innovations in orthopaedic science.

PMID- 24442841
TI  - When do patients with hand illness seek online health consultations and what do
      they ask?
AB  - BACKGROUND: Several websites allow people to post health questions and get
      answers from doctors. Knowing more about what patients seek from these websites
      might help in-office educational efforts, but little is known about what occurs
      on these sites. QUESTIONS/PURPOSES: This study addressed whether patients seeking
      advice online already have seen a physician, the type of questions asked, if they
      are dissatisfied with their doctor, the characteristics of the physicians who
      respond, and the content of their answers. This study documents the circumstances
      and content of questions asked about hand illness, the characteristics of the
      physician responders, and their responses. METHODS: One hundred thirty-one hand
      surgery-related questions from an online health consultation website were
      reviewed retrospectively. The timing of and reason for the consultation, the
      content of the questions, the specialty of physician responder, and the content
      of the responses were recorded. RESULTS: Sixty patients (46%) were seeking
      information before seeing a doctor, 21 (16%) after a medical encounter, and 19
      (15%) after hand surgery. With increasing contact with providers, patient queries
      transitioned from diagnosis, to treatment, to prognosis, and potential
      complications. Patients who had seen a doctor often expressed dissatisfaction (16
      of 37 patients [43%]) as did those who had hand surgery (seven of 26 patients
      [27%]). Between one and eight doctors (average, two) answered each query. Most of
      the answering physicians were hand surgeons. The information they provided
      predominantly addressed diagnosis. CONCLUSIONS: Online consultations are most
      common among patients who have not seen a doctor, but also reflect uncertainty
      and dissatisfaction after seeing a doctor. Although online health consultations
      might support patients' quest for information and understanding, and the
      potential for multiple answers from different doctors creates the possibility for
      increased balance and breadth of opinions, the quality of the information and
      cost-effectiveness of this approach are uncertain and need to be evaluated
      carefully in future studies.

PMID- 24442843
TI  - The art and angst of the mentoring relationship.
AB  - The authors review the ancient mentoring relationship in Homer's Odyssey and the
      mentoring discourse of Socrates. These relationships illustrate the art of
      inspiring a searching quality in the subject and the angst of the struggle that
      accompanies perplexity and unknowing. The developmental stages of the mentor and
      resident in psychiatric training are reviewed. A spectrum of teaching
      interventions are discussed as they might be perceived by the student. Finally,
      Plato's "Allegory of the Cave" is used as a metaphor for the art of enlightenment
      and angst of learning and teaching in the mentoring relationship. (Academic
      Psychiatry 1997; 21:61-71). 

PMID- 24442844
TI  - Managed care, health care reform, and academic psychiatry.
AB  - Although the process of national health care reform has slowed, state-based
      reform initiatives and market forces driven by managed care are dramatically
      reconfiguring the health care environment This decentralized process of health
      care reform poses numerous threats to academic departments of psychiatry, which
      must develop strategic plans to cope with the changes. The authors outline the
      effects of health care reform on clinical service, education, and research and
      discuss strategies of response in each domain, including examples from their
      department at Yale University. An active response to health care reform provides
      academic departments of psychiatry an opportunity to participate in shaping the
      future of psychiatry while reorganizing their teaching and research programs.
      (Academic Psychiatry 1997;21:72-85). 

PMID- 24442842
TI  - The epidemiology and injury patterns of acetabular fractures: are the USA and
      China comparable?
AB  - BACKGROUND: Acetabular fractures are rare injuries in heterogeneous patient
      groups, making it difficult to develop adequately powered prospective single
      center clinical trials in the USA or Europe. Chinese trauma centers treat a high
      volume of these injuries, and if the patient population and injury patterns are
      comparable to those in the USA, this might support development of multicenter
      studies in Level I trauma centers in the two countries. QUESTIONS/PURPOSES: We
      determined whether the following parameters were similar between operative
      acetabular fractures treated at Chinese and US trauma centers: (1) epidemiology
      of injured patients, (2) mechanism of injuries and fracture types, and (3)
      hospital stay parameters, including symptomatic postoperative deep vein
      thrombosis (DVT) rate. METHODS: We extracted data from trauma databases for
      patients admitted with acetabular fractures managed surgically from 2005 to 2012
      for one Chinese center and from 2008 to 2012 for one US center. Sex, age,
      mechanism of injury, fracture classification, Injury Severity Score (ISS), time
      from injury to surgery, length of hospital stay, and symptomatic DVT rate were
      analyzed. We included 661 Chinese patients (539 men, 122 women) and 212 US
      patients (163 men, 49 women). RESULTS: Mean age at time of injury was different
      between China and the USA, at 40 years with a unimodal distribution and 44 years
      with a bimodal distribution (p<0.001), respectively. Incidence of surgically
      treated acetabular fractures has been increasing in China but decreasing in the
      USA. Mean ISSs were comparable. Although the distribution of mechanisms of injury
      was different (p=0.004), high-energy injuries (motor vehicle accidents, falls>10
      feet) still accounted for most fractures in both centers. Fracture
      classifications (per Letournel) were comparable, with posterior wall fractures
      most common. Mean time from injury to surgery and mean hospital stay were longer
      in China than in the USA (9 versus 3 days [p<0.001] and 26 versus 11 days
      [p<0.001], respectively). Symptomatic DVT rates were comparable. CONCLUSIONS:
      Although we identified differences between the two centers, we also noted
      important similarities. Multicenter clinical studies involving these locations
      should be performed with caution and focus on similar end points, taking into
      account the populations' baseline differences. Because of the potential for such
      differences, this kind of validation study should be performed before embarking
      on resource-intensive multicenter trials. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24442845
TI  - Teaching students to identify psychosocial cues in problem-based learning cases.
AB  - This study's objective was to explore preclinical medical students' consideration
      of psychosocial variables in problem-based learning (PBL) cases. The authors used
      PBL cases that included psychosocial data and case content focused on behavioral
      science, biological science, or a combination of both. The authors compared,
      using one-way analysis of variance, the mean number of cues, learning issues, and
      hypotheses that the students generated in their written responses to PBL cases
      that varied in the amount of psychosocial content. The results revealed that the
      students identified psychosocial cues consistently across all curriculum
      segments, but the mean numbers of psychosocial hypotheses and learning issues
      were highest in the PBL case units dominated by psychosocial material. The
      authors conclude that the recognition of psychosocial data as germane disease
      variables is achieved more easily than the use of such data in a biopsychosocial
      formulation of traditional medical problems. A lack of sophistication and
      experience might make the latter task difficult to accomplish for many second
      year medical students without using specific educational strategies. 

PMID- 24442846
TI  - Incentives for teaching psychiatry.
AB  - A questionnaire was sent to chairs and faculty in 137 academic departments of
      psychiatry regarding the methods used to promote teaching and their perceived
      value. The incentives most often used included promotion and retention,
      nomination to committees, and peer recognition. Least often used were bonuses and
      a designated teachers' career track. Chairs and their faculty often disagreed as
      to whether some incentives were being used at all Recognition of teaching
      excellence was generally most highly valued as a useful incentive. Clarification
      of the nature and purpose of teaching incentives would likely improve their
      effectiveness. 

PMID- 24442847
TI  - Using narratives to evaluate psychiatry residents' competence.
AB  - The authors propose a new way to assess the clinical competence of psychiatric
      residents. Faculty eualuators would be trained by using narrative descriptions of
      appropriate and inappropriate practice in various clinical settings. The training
      has the potential to provide more realistic data about the clinical abilities of
      residents than current methods. 

PMID- 24442848
TI  - The evolution of a faculty development program in an academic psychiatry
      department.
AB  - Issues affecting faculty development in academic psychiatry departments have
      taken on a special urgency as a result of declining financial support from
      government sources and the emerging consequences of this country's fast-evolving
      health care system. Junior faculty need usable information on how to succeed in
      academia. Available information from the senior administration ("top-dawn") often
      lacks the immediacy and accessibility of grassroots ("bottom-up") strategies that
      more experienced junior colleagues have discovered. Over the past 2 years, the
      Department of Psychiatry at the University of Texas-Houston Health Science Center
      has focused attention on codifying these grassroots efforts and on integrating
      them with formal departmental initiatives. The authors describe how general
      recommendations formulated by departmental planning committees and a Continuous
      Quality Improvement Team on faculty development were developed into a formal,
      concrete program f or career development. (Academic Psychiatry 1997; 21:107-115).

PMID- 24442849
TI  - Recruitment into psychiatry.

PMID- 24442850
TI  - Introducing community service into psychiatry residency education.

PMID- 24442852
TI  - ZNF804A protein is widely expressed in human brain neurons: possible implications
      on normal brain structure and pathomorphologic changes in schizophrenia.

PMID- 24442853
TI  - Neural effects of the social environment.
AB  - Epidemiological studies have suggested that the association between city
      upbringing and minority status with risk for schizophrenia can be explained by
      social mechanisms. Neuroimaging approaches hold promise for investigating this
      claim. Recent studies have shown that in healthy individuals, city upbringing and
      minority status are associated with increased activity in brain circuits involved
      in emotion regulation during social evaluative processing. These findings support
      the hypothesis that changes in the ability to regulate social stress contribute
      to the mechanism of risk. This is in accordance with a body of evidence
      demonstrating the sensitivity of the human brain to social stress, based on
      observational studies investigating the neurological sequelae of interpersonal
      trauma and experimental studies manipulating exposure to interpersonal distress.
      In this report, we summarize these initial findings, discuss methodological and
      conceptual challenges of pursuing this line of inquiry in schizophrenia, and
      suggest an outline for future research. 

PMID- 24442851
TI  - Partial genetic deletion of neuregulin 1 modulates the effects of stress on
      sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent
      mice.
AB  - Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in
      neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help
      predict which high-risk individuals will transition to psychosis. NRG1 also
      modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal
      model to demonstrate that partial genetic deletion of Nrg1 interacts with stress
      to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1
      heterozygous (HET) mice displayed greater acute stress-induced anxiety-related
      behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the
      normal development of higher prepulse inhibition of startle selectively in Nrg1
      HET mice but not in WT mice. Further, repeated stress increased dendritic spine
      density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively
      in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive
      response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1
      HET displaying a reduced repeated stress-induced level of plasma corticosterone
      than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated
      stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC,
      and an abberant endocrine response in adolescence. 

PMID- 24442854
TI  - Unique crystal structure of a novel surfactant protein from the foam nest of the
      frog Leptodactylus vastus.
AB  - Breeding by releasing eggs into stable biofoams ("foam nests") is a peculiar
      reproduction mode within anurans, fish, and tunicates; not much is known
      regarding the biochemistry or molecular mechanisms involved. Lv-ranaspumin (Lv
      RSN-1) is the predominant protein from the foam nest of the frog Leptodactylus
      vastus. This protein shows natural surfactant activity, which is assumed to be
      crucial for stabilizing foam nests. We elucidated the amino acid sequence of Lv
      RSN-1 by de novo sequencing with mass-spectrometry and determined the high
      resolution X-ray structure of the protein. It has a unique fold mainly composed
      of a bundle of 11 alpha-helices and two small antiparallel beta-strands. Lv-RSN-1
      has a surface rich in hydrophilic residues and a lipophilic cavity in the region
      of the antiparallel beta-sheet. It possesses intrinsic surface-active properties,
      reducing the surface tension of water from 73 to 61 mN m(-1) (15 MUg mL(-1)). Lv
      RSN-1 belongs to a new class of surfactants proteins for which little has been
      reported regarding structure or function.

PMID- 24442855
TI  - Early gene expression changes in skeletal muscle from SOD1(G93A) amyotrophic
      lateral sclerosis animal model.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by loss of motor neurons. Familial ALS is strongly associated to dominant
      mutations in the gene for Cu/Zn superoxide dismutase (SOD1). Recent evidences
      point to skeletal muscle as a primary target in the ALS mouse model. Wnt/PI3 K
      signaling pathways and epithelial-mesenchymal transition (EMT) have important
      roles in maintenance and repair of skeletal muscle. Wnt/PI3 K pathways and EMT
      gene expression profile were investigated in gastrocnemius muscle from SOD1(G93A)
      mouse model and age-paired wild-type control in the presymptomatic ages of 40 and
      80 days aiming the early neuromuscular abnormalities that precede motor neuron
      death in ALS. A customized cDNA microarray platform containing 326 genes of
      Wnt/PI3 K and EMT was used and results revealed eight up-regulated (Loxl2,
      Pik4ca, Fzd9, Cul1, Ctnnd1, Snf1lk, Prkx, Dner) and nine down-regulated (Pik3c2a,
      Ripk4, Id2, C1qdc1, Eif2ak2, Rac3, Cds1, Inppl1, Tbl1x) genes at 40 days, and
      also one up-regulated (Pik3ca) and five down-regulated (Cd44, Eef2 k, Fzd2,
      Crebbp, Piki3r1) genes at 80 days. Also, protein-protein interaction networks
      grown from the differentially expressed genes of 40 and 80 days old mice have
      identified Grb2 and Src genes in both presymptomatic ages, thus playing a
      potential central role in the disease mechanisms. mRNA and protein levels for
      Grb2 and Src were found to be increased in 80 days old ALS mice. Gene expression
      changes in the skeletal muscle of transgenic ALS mice at presymptomatic periods
      of disease gave further evidence of early neuromuscular abnormalities that
      precede motor neuron death. The results were discussed in terms of initial
      triggering for neuronal degeneration and muscle adaptation to keep function
      before the onset of symptoms.

PMID- 24442856
TI  - High-flow nasal cannula therapy for infants with bronchiolitis.
AB  - BACKGROUND: Bronchiolitis is a common lower respiratory tract illness, usually of
      viral aetiology, affecting infants younger than 24 months of age and is a
      frequent cause of hospitalisation. It causes airway inflammation, mucus
      production and mucous plugging, resulting in airway obstruction. Effective
      pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and
      mortality.Conventional treatment consists of supportive therapy in the form of
      fluids, supplemental oxygen and respiratory support. Traditionally oxygen
      delivery is as a dry gas at 100% concentration via low-flow nasal prongs.
      However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy
      enables delivery of higher inspired gas flows of an air/oxygen blend, up to 12
      L/min in infants and 30 L/min in children. Its use provides some level of
      continuous positive airway pressure to improve ventilation in a minimally
      invasive manner. This may reduce the need for invasive respiratory support thus
      potentially lowering costs, with clinical advantages and fewer adverse effects.
      OBJECTIVES: To assess the effects of HFNC therapy compared with conventional
      respiratory support in the treatment of infants with bronchiolitis. SEARCH
      METHODS: We searched CENTRAL (2013, Issue 4), MEDLINE (1946 to May week 1, 2013),
      EMBASE (January 2010 to May 2013), CINAHL (1981 to May 2013), LILACS (1982 to May
      2013) and Web of Science (1985 to May 2013). In addition we consulted ongoing
      trial registers and experts in the field to identify ongoing studies, checked
      reference lists of relevant articles and searched conference abstracts. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs which
      assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow
      rates greater than 4 L/min) compared to conventional treatment in infants (< 24
      months) with a clinical diagnosis of bronchiolitis. DATA COLLECTION AND ANALYSIS:
      Two review authors independently used a standard template to assess trials for
      inclusion and extract data on study characteristics, 'Risk of bias' elements and
      outcomes. We contacted trial authors to request missing data. Outcome measures
      included the need for invasive respiratory support and time until discharge,
      clinical severity measures, oxygen saturation, duration of oxygen therapy and
      adverse events. MAIN RESULTS: We included one RCT which was a pilot study with 19
      participants that compared HFNC therapy with oxygen delivery via a head box. In
      this study, we judged the risk of selection, attrition and reporting bias to be
      low, and we judged the risk of performance and detection bias to be unclear due
      to lack of blinding. The median oxygen saturation (SpO2) was higher in the HFNC
      group at eight hours (100% versus 96%, P = 0.04) and at 12 hours (99% versus 96%,
      P = 0.04) but similar at 24 hours. There was no clear evidence of a difference in
      total duration of oxygen therapy, time to discharge or total length of stay
      between groups. No adverse events were reported in either group and no
      participants in either group required further respiratory support. Five ongoing
      trials were identified but no data were available in May 2013. We were not able
      to perform a meta-analysis. AUTHORS' CONCLUSIONS: There is insufficient evidence
      to determine the effectiveness of HFNC therapy for treating infants with
      bronchiolitis. The current evidence in this review is of low quality, from one
      small study with uncertainty about the estimates of effect and an unclear risk of
      performance and detection bias. The included study provides some indication that
      HFNC therapy is feasible and well tolerated. Further research is required to
      determine the role of HFNC in the management of bronchiolitis in infants. The
      results of the ongoing studies identified will contribute to the evidence in
      future updates of this review.

PMID- 24442857
TI  - The role of intraoperative ultrasound in breast-conserving surgery of nonpalpable
      breast cancer.
AB  - OBJECTIVE: This retrospective study was undertaken to evaluate the role of
      intraoperative ultrasound in breast-conserving surgery of nonpalpable breast
      cancer. METHODS: The data about 125 patients with preoperatively diagnosed breast
      cancer operated with the help of intraoperative ultrasound between January 2009
      and December 2012 were retrospectively analyzed. RESULTS: The mean volume of the
      excised tissue was 42.1 cm(3) (+/- 22.0 cm(3)). Immediate re-excision after
      ultrasound examination of the excised tissue was performed in 27 patients (21.6
      %). Secondary procedure owing to positive histological margins was necessary only
      in four patients (3.2 %). CONCLUSIONS: Intraoperative ultrasound offers some
      advantages in comparison with other localization techniques for nonpalpable
      breast cancer surgery.

PMID- 24442858
TI  - Evaluation of treatment responses and colony-forming progenitor cells in 50
      patients with aplastic anemia after immunosuppressive therapy or hematopoietic
      stem cell transplantation: a single-center experience.
AB  - We analyzed the clinical course and outcome in 50 patients (27 males, 23 females)
      suffering from aplastic anemia (AA), treated in our department between 1987 and
      2007. The median age was 37 years (range: 14-70 years). A total of 42 patients
      received antithymocyte globulin and cyclosporine A (CSA). Seven patients were
      transplanted using a matched sibling donor upfront, and one patient was treated
      with CSA and growth factors only. A total of 34 patients (68 %) achieved a
      complete remission, and 7 (14 %), a partial remission. Eight patients (16 %) did
      not respond to treatment, and one died shortly after transplantation. Relapses of
      AA occurred in eight patients (20 %). No obvious correlations between clinical
      parameters, including age, karyotype, existence of paroxysmal nocturnal
      hemoglobinuria clones, pretreatment blood counts, progenitor cell counts, and the
      response to immunosuppressive therapy (IST), were found. We also examined the
      numbers of colony-forming progenitor cells (CFUs) before and after therapy. In
      most responding patients, CFU numbers increased substantially after successful
      therapy. However, even in patients without a substantial increase in CFU, stable
      remissions were observed. Together, both IST and stem cell transplantation are
      reasonable treatment options for patients with AA. 

PMID- 24442859
TI  - Migration characteristics and early clinical results of a novel-finned press-fit
      acetabular cup.
AB  - BACKGROUND: Ana Nova(r) is a novel-finned press-fit acetabular cup which showed
      superior biomechanical characteristics in an experimental set-up. Using Einzel
      Bild Rontgen Analyse (EBRA) measurements should offer the opportunity to predict
      implant survival at an early stage. The purpose of this study was to assess
      migration and clinical outcome 2 years after total hip replacement by a novel
      finned press-fit acetabular cup. METHODS: In this study, migration and clinical
      results of the implant were prospectively assessed in 67 patients. Clinical
      outcome was assessed using the Harris hip score (HHS). Migration analyses were
      performed using the computer assisted EBRA system. Data were analyzed for normal
      distribution using the Kolmogorov-Smirnov test. Group comparisons were performed
      using the analysis of variance (ANOVA) test. P-values less than 0.05 were
      considered statistically significant. RESULTS: At 2 years after surgery, none of
      the implants needed revision and HHS increased from 39.7 up to 92.2. In contrast
      to the beneficial clinical outcome, 17 of 44 patients showed increased total
      migration ( 1 mm/2a). CONCLUSIONS: Adverse migration data in this study might
      predict aseptic loosening and decreased survival of the implant. According to
      previous studies, it is possible that this effect occurred because of limited
      accuracy of the EBRA system. In our opinion, migration analyses may not be
      recommended as a screening tool in a 2 year follow-up.

PMID- 24442860
TI  - Mean platelet volume and red blood cell distribution width in prognosis of
      chronic hepatitis B.

PMID- 24442861
TI  - Human immunodeficiency virus type 2 infections in Austria.
AB  - INTRODUCTION: The first case of human immunodeficiency virus type 2 (HIV-2)
      seropositivity in Austria was confirmed in 1993 in a dually human
      immunodeficiency virus type 1 (HIV-1)- and HIV-2-infected patient from Ghana, who
      died in 2001. Before this investigation, no further HIV-2 infection was
      published. METHODS: The aim of this study was to describe HIV-2 epidemiology in
      Austria, using serological and molecular techniques, and to perform a sequence
      analysis of the circulating viral strains. RESULTS: Six additional cases of HIV-2
      were identified from 2000 to 2009. All patients originated from high-prevalence
      areas. In one patient, the HIV-2 infection was revealed 11 years after initial
      HIV-1 diagnosis, and further analysis confirmed a dual infection. CONCLUSION: The
      HIV-2 epidemic has its epicentre in West Africa, but sociocultural issues,
      especially migration, are contributing to the low but continuous worldwide spread
      of HIV-2. Diagnosis of HIV-2 implies a different therapeutical management to
      avoid treatment failure and clinical progression. Differential diagnosis of HIV-1
      and HIV-2 is complicated due to antibody cross-reactivity, and paradoxical
      findings (e.g. declining CD4 cell count despite HIV-1 suppression) may require
      careful reassessment, especially in patients from endemic countries.

PMID- 24442862
TI  - Q-band electron paramagnetic resonance dosimetry in tooth enamel: biopsy
      procedure and determination of dose detection limit.
AB  - High-frequency Q-band (37 GHz) electron paramagnetic resonance (EPR) dosimetry
      allows to perform fast (i.e., measurement time <15 min) dose measurements using
      samples obtained from tooth enamel mini-biopsy procedures. We developed and
      tested a new procedure for taking tooth enamel biopsy for such dose measurements.
      Recent experience with EPR dose measurements in Q-band using mini-probes of tooth
      enamel has demonstrated that a small amount of tooth enamel (2-10 mg) can be
      quickly obtained from victims of a radiation accident. Accurate dose assessments
      can further be carried out in a very short time to provide important information
      for medical treatment. Here, the Q-band EPR dose detection limit for 5 and 10 mg
      samples is estimated to be 367 and 248 mGy, respectively. These values are
      comparable to the critical parameters determined for conventional X-band EPR in
      tooth enamel.

PMID- 24442863
TI  - Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone
      tissue of apolipoprotein-E knockout mice with chronic kidney disease.
AB  - Vascular calcification (VC) is a risk factor for cardiovascular mortality in the
      setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous
      molecule that inhibits hydroxyapatite crystal formation, has been shown to
      prevent the development of VC in animal models of CKD. However, the possibility
      of harmful effects of exogenous administration of PPi on bone requires further
      investigation. To this end, we examined by histomorphometry the bone of CKD mice
      after intraperitoneal PPi administration. After CKD creation or sham surgery, 10
      week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one
      non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three
      distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals
      were killed. Serum and femurs were sampled. Femurs were processed for bone
      histomorphometry. Placebo-treated CKD mice had significantly higher values of
      osteoid volume, osteoid surface and bone formation rate than sham-placebo mice
      with normal renal function. Slightly higher osteoid values were observed in CKD
      mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one
      parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD
      mice. Treatment with PPi did not modify any other structural parameters. Mineral
      apposition rates, and other parameters of bone formation and resorption were not
      significantly different among the treated animal groups or control CKD placebo
      group. In conclusion, PPi does not appear to be deleterious to bone tissue in
      apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid
      formation may be worth further investigation.

PMID- 24442865
TI  - Structural and functional substrates of tetanus toxin in an animal model of
      temporal lobe epilepsy.
AB  - The effects of tetanus toxin (TeNT) both in the spinal cord, in clinical tetanus,
      and in the brain, in experimental focal epilepsy, suggest disruption of
      inhibitory synapses. TeNT is a zinc protease with selectivity for Vesicle
      Associated Membrane Protein (VAMP; previously synaptobrevin), with a reported
      selectivity for VAMP2 in rats. We found spatially heterogeneous expression of
      VAMP1 and VAMP2 in the hippocampus. Inhibitory terminals in stratum pyramidale
      expressed significantly more VAMP1 than VAMP2, while glutamatergic terminals in
      stratum radiatum expressed significantly more VAMP2 than VAMP1. Intrahippocampal
      injection of TeNT at doses that induce epileptic foci cleaved both isoforms in
      tissue around the injection site. The cleavage was modest at 2 days after
      injection and more substantial and extensive at 8 and 16 days. Whole-cell
      recordings from CA1 pyramidal cells close to the injection site, made 8-16 days
      after injection, showed that TeNT decreases spontaneous EPSC frequency to 38 % of
      control and VAMP2 immunoreactive axon terminals to 37 %. In contrast, TeNT almost
      completely abolished both spontaneous and evoked IPSCs while decreasing VAMP1
      axon terminals to 45 %. We conclude that due to the functional selectivity of the
      toxin to the relative sparing of excitatory synaptic transmission shifts the
      network to pathogenically excitable state causing epilepsy. 

PMID- 24442866
TI  - Dorsal hippocampal brain receptor complexes linked to the protein synthesis
      dependent late phase (LTP) in the rat.
AB  - In order to link major brain receptor complex levels to in vivo electrically
      induced LTP, a bipolar stimulation electrode was chronically implanted into the
      perforant path, while two monopolar recording electrodes were implanted into the
      dentate gyrus of the dorsal hippocampus. The recording electrode was measuring
      extracellular excitatory postsynaptic potentials, while the other one measured
      population spikes. Immunoblotting of native receptor proteins was carried out in
      the DH based upon blue-native gel electrophoresis and immunoprecipitation
      followed by mass spectrometrical identification of the NR1-GluA1-GluA2 complex
      was used to provide evidence for complex formation. The induction of LTP in DH
      was proven and NMDA receptor complex levels containing NR1, GluA1, GluA2 and
      GluA3 were modulated by LTP induction. The LTP-associated changes of receptor
      complex levels may indicate concerted action, interaction and represent a pattern
      of major brain receptor complexes in the DH following electrical induction of LTP
      in the rat. 

PMID- 24442867
TI  - A semi-quantitative approach to variation of the azygos vein course.
AB  - The azygos vein (AV) is typically described (illustrated) as ascending vertically
      on the right of thoracic vertebrae. Most thoracic vein studies have focused on
      tributary patterns, but some have noted more leftward AV courses. This study
      statistically documents variation in AV course independent of tributary patterns.
      A more statistical approach to the probable position of AV at different vertical
      levels may aid clinicians in locating and assessing it in clinical contexts. The
      AV course was exposed in 84 cadavers by removing overlying viscera between the
      aortic hiatus and tracheal bifurcation. Subjectively, non-pathological specimens
      were digitally photographed in anterior view. For each photo, a scaled grid was
      used to mark the horizontal position of the AV center at each of five vertical
      levels. The summated numerical distributions showed the following: ~5% of the AVs
      ascended on the right side (classical) position, ~30% did not cross the midline,
      ~70% included part or all of their course left of the midline, and ~14% reached
      the extreme left side. Based on this data, the modal AV course (1) begins at, or
      to the right of, the midline, (2) deviates leftward, (3) crosses the midline
      below mid-level, (4) reaches a leftward maximum at about 3/5 of its course, (5)
      then deviates rightward (often only reaching the midline at the uppermost level).
      In several noticeable cases, the leftward maximum was associated with large
      connections to left-side veins, suggesting a possible tension mechanism exerting
      traction on the AV over time.

PMID- 24442868
TI  - Nucleolin involved in myocardial ischaemic preconditioning via post
      transcriptional control of HSPA1A expression.
AB  - AIMS: Recent studies have identified the critical roles of nucleolin in a variety
      of cellular processes, including regulation of viral replication and tumour
      formation. However, the possible roles of nucleolin in myocardial preconditioning
      remain undefined. METHODS AND RESULTS: We used an in vivo rat myocardial
      ischaemic preconditioning (IP) model (four cycles of 5 min ischaemia and 10 min
      reperfusion) and cellular hydrogen peroxide preconditioning (H2O2-PC) models. We
      found that nucleolin mRNA and protein expression showed a time-dependent increase
      during the recovery of myocardial ischaemic preconditioning in rats and H2O2-PC
      in neonatal rat cardiomyocytes. Nucleolin overexpression enhanced the protective
      effects of H2O2-PC, whereas nucleolin ablation abrogated the H2O2-PC-mediated
      protection in cardiomyocytes. On the other hand, nucleolin overexpression
      increased the stabilization of the HSPA1A mRNA and the expression of HSPA1A
      protein in cardiomyocytes, whereas nucleolin ablation abrogated the up-regulation
      of HSPA1A induced by H2O2-PC in cardiomyocytes. An interaction between nucleolin
      and HSPA1A mRNA was further identified using the RNA-protein interaction studies.
      Reporter gene assays, which depended on the untranslated regions (UTR) of HSPA1A
      mRNA, revealed that the post-transcriptional regulation was mainly attributed to
      the 3' UTR. Finally, HSPA1A anti-sense oligonucleotides (asODNs) attenuated the
      protective effect of nucleolin in cardiomyocytes. CONCLUSION: These results
      indicate that nucleolin is up-regulated and involved in myocardial protection of
      ischaemic preconditioning via a post-transcriptional control of HSPA1A
      expression.

PMID- 24442869
TI  - Silencing of Pellino1 improves post-infarct cardiac dysfunction and attenuates
      left ventricular remodelling in mice.
AB  - AIMS: Pellino1 is an evolutionally conserved immune regulator and participates in
      the regulation of Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated
      signalling. Recent studies have shown that TLR/IL-1R contributes to the left
      ventricular (LV) remodelling after myocardial infarction (MI). However, the role
      of Pellino1 in LV remodelling following MI has not been investigated. This study
      examined the effect of Pellino1 silencing on cardiac function and LV remodelling
      after MI. METHODS AND RESULTS: Male C57BL/6 mice were subjected to permanent
      ligation of left anterior descending coronary artery (LAD) to induce MI. The
      levels of Pellino1 were significantly increased in the myocardium 3 days and
      sustained for 4 weeks after MI, when compared with the sham control. Hypoxia
      increased Pellino1 expression in cultured cardiomyocytes and fibroblasts. To
      examine whether Pellino1 plays a role in MI-induced cardiac dysfunction and the
      LV remodelling, we suppressed the expression of Pellino1 either by
      intramyocardial delivery of adenovirus expressing siRNA for Pellino1 (AdsiPeli1)
      or by Cre-LoxP-mediated conditional deletion of Pellino1 from the myocardium. In
      both models, silencing of Pellino1 significantly attenuated MI-induced cardiac
      dysfunction, decreased scar size, and reduced collagen deposition, when compared
      with the control groups. Pellino1 silencing in mice also attenuated MI-induced
      Pellino1 E3 ligase activity, receptor-interacting protein 1 and tumor necrosis
      factor receptor associated factor 6 (TRAF6) ubiquitination, nuclear factor Kappa
      B (NF-kappaB) activity, cytokine production, and inflammatory cell infiltration
      into the myocardium when compared with the MI group. CONCLUSIONS: Our data
      demonstrate that Pellino1 plays an important role in the pathogenesis of MI.
      Targeting Pellino1 may ameliorate cardiac dysfunction and remodelling following
      MI.

PMID- 24442870
TI  - Electron transfer in photosystem II.
AB  - The picture presently emerging from studies on the mechanism of photosystem II
      electron transport is discussed. The reactions involved in excitation trapping,
      charge separation and stabilization of the charge pair in the reaction center,
      followed by the reactions with the substrates, plastoquinone reduction and water
      oxidation, are described successively. Finally, a brief discussion on photosystem
      II heterogeneity is presented. 

PMID- 24442871
TI  - Ferredoxin-NADP(+) reductase, a nuclearly-coded enzyme unaffected by tentoxin
      treatment.
AB  - Previous studies in our laboratory have shown that tentoxin prevents the
      incorporation of polyphenol oxidase (PPO), a nuclearly-coded protein, into the
      chloroplasts of sensitive species. In this study, we show, by comparison of
      electrophoretically separated isozymes, that ferredoxin-NADP(+) reductase (FNR)
      is nuclearly coded in Nicotiana. Electrophoresis of FNR isozymes from tentoxin
      treated seedlings of a sensitive and a resistant species demonstrated that,
      unlike PPO, ferredoxin-NADP(+) reductase was unaffected by tentoxin treatment.
      These data indicate that tentoxin selectively inhibits transport of
      cytoplasmically synthesized proteins into the chloroplast, and does not produce a
      generalized disruption of cellular integration. 

PMID- 24442872
TI  - The recovery of photosynthesis in tomato subsequent to chilling exposure.
AB  - The overall success of a plant in coping with low temperature sensitivity of
      photosynthesis is dependent not only on the maximum extent of inhibition suffered
      for a given time of low temperature exposure but also on the persistence of the
      inhibition after normal growth temperatures are restored. Thus the capacity of
      recovery and the speed with which a plant can recover from the effects of
      chilling exposure are important parameters in determining how devastating the
      chilling event will be on season-long growth and yields. We have studied the
      recovery of CO2-saturated photosynthesis from the injury caused by exposing
      intact tomato plants (Lycopersicon esculentum Mill. cv. Floramerica) or detached
      tomato leaves to a temperature of 1 degrees C in the dark for varying periods of
      time. We found that net photosynthesis was fully recovered within 12 h after
      returning the plants to 25 degrees C in the dark, even after chilling exposures
      as long as 45 h. This was true for intact plants as well as for detached leaves
      that were supplied with water. When chilling took place in the light (4 degrees
      C, 1000 MUE . m(-2) . s(-1), PAR) inhibition of photosynthesis was more severe
      and appeared more quickly and the recovery was slower and incomplete. A 12 h
      chilling exposure in the light resulted in injury to net photosynthesis that was
      not fully recovered even after 50 h. Chilling damage to photosynthesis developing
      in the light was distinguished from chilling in the dark by the decreased
      photosynthetic quantum yield. Not only did high intensity illumination enhance
      chilling damage of photosynthesis but bright light subsequent to the chilling
      exposure also delayed the recovery of photosynthesis. At none of the three
      ambient CO2 concentrations investigated (300, 1500 and 5000 MU1.1(-1)) did the
      recovery of photosynthesis depend on stomatal conductance. 

PMID- 24442873
TI  - Influence of structural and physical properties of the thylakoid membrane on QA (
      ) oxidation.
AB  - Using isolated pea thylakoids, the relative rate of QA (-) oxidation has been
      estimated under various conditions, from the restoration of the induction curves
      following a dark period and from light 1-induced changes in modulated chlorophyll
      fluorescence excited by light 2.Alterations of QinfA (sup-) oxidation rates were
      observed under conditions which affected the degree of thylakoid stacking, the
      lipid fluidity and the integrity of the membranes. The results are discussed in
      terms of the interactions between QA (-) and the plastoquinone pool with
      particular emphasis on lateral diffusion. 

PMID- 24442874
TI  - Effects of root applications of gibberellic acid on photosynthesis and growth in
      C3 and C 4 plants.
AB  - The effects of root applications of gibberellic acid (GA3) on growth and
      photosynthesis of 12 species of plants including C3 monocots (Triticum aestivum
      L., wheat, Hordeum vulgare L., barley and Avena sativa L., oat), C3 dicots (Vigna
      radiata L., mung bean, Cucurbita moschata L., squash and Capsicum annuum L.,
      pepper), C4 monocots (Zea mays L., corn, Sorghum vulgare L., sorghum and Panicum
      ramosum L., millet) and C4 dicots (Amaranthus retroflexus L., pigweed, Kochia
      scoparis L., kochia and Gomphrena celosoides L., gomphrena) were evaluated.
      Relative growth rates (RGR) of barley, oat, squash, pepper, corn, sorghum,
      millet, pigweed and kochia were increased above the control by 12.7%, 9.9%,
      11.3%, 10.7%, 19.2% 10.1%, 11.5%, 16.4% and 32.7% respectively, four days
      following optimum GA3 treatments. There was no effect of GA3 on RGR in wheat,
      mung bean, and gomphrena. Gibberellic acid decreased the chlorophyll content
      expressed on an area basis by 20.0%, 13.9%, 20.9%, 17.1%, 11.9% and 28.0% in
      barley, squash, pepper, sorghum, pigweed and kochia, respectively, while that of
      oat, wheat, mung bean, corn, millet and gomphrena remained unchanged. When
      photosynthetic rates were expressed per mg of chlorophyll, it showed that GA3
      could stimulate photosynthesis in barley, squash, pepper, sorghum, millet,
      pigweed and kochia by 20.4%, 20.6%, 16.5%, 17.4%, 10.4%, 24.2%, and 29.4%; while
      there was no effect in oat, wheat, mung bean, corn and gomphrena. An increase in
      leaf blade area and/or length of sheath were observed in GA3 treated plants of
      oat, barley, mung bean, squash, pepper, corn, sorghum, millet and kochia. The
      transpiration rate remained unchanged following GA3 treatment in all 12 species. 

PMID- 24442875
TI  - Functional and structural organization of chlorophyll in the developing
      photosynthetic membranes of Euglena gracilis Z. V-separation and characterization
      of pigment-protein complexes of the differentiated thylakoids.
AB  - Low temperature sodium dodecyl sulfate polyacrylamide gel electrophoresis
      following mild solubilization of Euglena thylakoid components allowed to resolve,
      in addition to the main CP1, CPa and LHCP chlorophyll-protein complexes, the
      additional CP1a and LHCP' green bands. A carotenoid enriched band CPc can be
      separated from CPa using high acrylamide concentration. Pigment and polypeptide
      composition of these complexes were analyzed by absorption and fluorescence
      measurements and two dimensional gel electrophoresis. Spectral properties of CP1
      and CP1a indicate an heterogenous organization of chlorophyll and the presence of
      significant amount of chlorophyll b in these complexes. They both contain a major
      68 kilodalton polypeptide associated with three minor low molecular weight
      polypeptides in CP1a. CPa and CPc exhibit a characteristic fluorescence emission
      at 687 nm and they each contain one polypeptide of 54 and 41 Kda respectively.
      LHCP and LHCP' are less abundant than in higher plant thylakoids and they contain
      a lower proportion of chl b (chl a: chl b=3). They include two polypeptides of 26
      and 29 Kda. 

PMID- 24442876
TI  - Effects of day and night temperature and temperature variation on photosynthetic
      characteristics.
AB  - Net photosynthetic rates and mesophyll conductances were measured under
      standardized conditions for leaves of two C3 and one C4 annual species grown at
      temperatures of 20 to 32 degrees C. Plants were grown with varying day and night
      temperatures, and also at constant temperatures equal to all the day and night
      temperatures used. Plants were grown with 8, 12, and 16 hours of light per day.
      This design allowed determination of whether photosynthetic characteristics were
      best correlated with day, night, mean, or time-weighted mean temperatures, The
      results showed that for Glycine max (L.) Merr. (C3) night temperature was most
      important in determining photosynthetic characteristics, while in Helianthus
      annuus L. (C3) and Amaranthus hypochondriacus L. (C4) the time-weighted mean
      temperature was most important. The results for all species were consistent with
      the hypothesis that development of photosynthetic characteristics is related to a
      balance between the rate of leaf expansion and the rate of photosynthesis under
      the growth conditions. 

PMID- 24442877
TI  - Multiple forms of P700-chlorophyll a-protein complexes from Synechococcus sp.:
      The iron, quinone and carotenoid contents.
AB  - The iron, quinone and carotenoid contents of five P700-chlorophyll a-protein
      complexes having different subunit structures (CP1-a,-b,-c,-d and-e) from the
      thermophilic cyanobacterium Synechococcus sp. were determined. CP1-a,-b,-c and-d
      that commonly have four polypeptides of 62,000, 60,000, 14,000 and 10,000 dalton
      contained 10-14 iron atoms per P700, whereas CP1-e that lacks the two small
      polypeptides was totally devoid of iron. All CP1 complexes contained vitamin K1
      at the molar ratio of vitamin K1 to P700 of about 2 except CP1-e that had only
      0.4 vitamin K1 per P700. No plastoquinone was detected in five CP1 complexes. Out
      of four major carotenoids, beta-carotene, zeaxanthin, caloxanthin, and
      myxoxanthophyll, present in the thylakoid membranes, only beta-carotene was found
      in isolated CP1 complexes; all CP1 complexes contained about 10 beta-carotene
      molecules per P700. The flourescence excitation spectrum showed that beta
      carotene serves as an efficient antenna of photosystem I. It is concluded that
      all iron atoms and a larger fraction of vitamin K1 molecules present in the
      photosystem I reaction center complex are associated with the 14,000 and 10,000
      dalton polypeptides, whereas beta-carotene exclusively binds to the large
      polypeptides which carry the functional and antenna chlorophyll a. The possible
      functions of iron and vitamin K1 as electron carriers and of beta-carotene as the
      accessary pigment and a photoprotectant in the photosystem I complexes are
      discussed. 

PMID- 24442878
TI  - The use of polyclonal antibodies to identify peptides exposed on the stroma side
      of the spinach thylakoid.
AB  - We have raised polyclonal antibodies against an oxygen-evolving photosystem II
      preparation. Western Blot analysis of the whole serum revaals antibodies specific
      for at least 15 Coomassie visible bands ranging from 59 to 11 kDa. These
      antibodies are specific for proteins located on both sides of the membrane.
      Included are antibodies specific for Tris-removable peptides (33, 25 and 18 kda),
      which are thought to be exposed on the lumen surface of the PS II complex. Since
      the whole serum agglutinates thylakoids, antibodies specific for the stroma side
      of the PS II complex are also present. A sub-population of antibodies can be
      isolated by allowing the antibodies in whole serum to bind to EDTA-treated
      thylakoid membranes. The antibodies which specifically bind are cross-reactive
      with peptides with Mr of 59, 57, 34, 28, 27, 26, and 23 kDa. Our data indicate
      that these peptides have antigenic determinants exposed on the stroma side of the
      thylakoid membrane. 

PMID- 24442879
TI  - Significant associations of antidrug antibody levels with serum drug trough
      levels and therapeutic response of adalimumab and etanercept treatment in
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the associations between (1) antidrug antibody (ADAb) and
      therapeutic response, (2) ADAb and serum drug trough levels and (3) serum drug
      levels and therapeutic responses in rheumatoid arthritis (RA) patients receiving
      adalimumab or etanercept. Secondarily, we aim (1) to evaluate the concordance
      between radioimmunoassay and bridging ELISA for ADAb assessment and to evaluate
      the correlation between two different ELISA methods for detecting drug levels,
      and (2) to determine the optimal cut-off drug levels for good European League
      Against Rheumatism (EULAR) response. METHODS: ADAb levels were determined by
      bridging ELISA and radioimmunoassay, and drug levels evaluated using sandwich
      ELISA among 36 adalimumab-treated patients and 34 etanercept-treated patients at
      the 6th and 12th month. The optimal cut-off drug levels for EULAR responses were
      determined by receiver-operating characteristic curve analysis. RESULTS: ADAb was
      detected in 10 (27.8%) and 13 (36.1%) of adalimumab-treated patients after 12
      month therapy using bridging ELISA and radioimmunoassay respectively, but not
      detected in any of etanercept-treated patients. The presence of ADAb was
      associated with lower EULAR response and lower drug levels compared with those
      without ADAb (both p<0.001). Drug trough levels were positively associated with
      DAS28 decrement (DeltaDAS28) (all p<0.001). The optimal cut-off trough levels for
      adalimumab were 1.274 MUg/mL and 1.046 MUg/mL, and those for etanercept were
      1.242 MUg/mL and 0.800 MUg/mL for good EULAR response assessed at the 6th and
      12th month, respectively. CONCLUSIONS: ADAb levels were inversely correlated with
      therapeutic response and drug levels. The positive correlation between drug
      levels and DeltaDAS28 indicates that drug monitoring would be useful to evaluate
      therapeutic response of TNF-alpha inhibitors.

PMID- 24442881
TI  - Incidence and mortality rates of biopsy-proven giant cell arteritis in southern
      Sweden.
AB  - OBJECTIVES: To study the epidemiology and mortality in patients with biopsy
      proven giant cell arteritis (GCA) in southern Sweden. METHODS: The study area was
      the County of Skane. Patients with a positive temporal artery biopsy between 1997
      and 2010 were identified using a regional register and a structured review of all
      histopathology reports. Standardised mortality ratios (SMR) were calculated using
      data for the Swedish population as the reference. RESULTS: There were 840
      patients with biopsy-proven GCA (626 women). The annual incidence rate per
      100,000 inhabitants aged >=50 years was 14.1 (95% CI 13.1 to 15.0); 7.7 (6.7 to
      8.7) for men and 19.6 (18.1 to 21.1) for women, without seasonal variations. The
      incidence increased with age, with estimates of 2.0, 11.8, and 31.3 per 100,000
      in the age groups 50-60, 61-70, 71-80 years, respectively (p<0.001). The age
      standardised and sex-standardised incidence rate decreased from 15.9/100,000 in
      1997-2001 to 13.3/100,000 in 2007-2010 (p=0.026). Two hundred and seventy-nine
      patients (207 women) died during the observation period. Mortality was
      significantly increased over the first 2 years after GCA diagnosis (SMR 1.52 (95%
      CI 1.20 to 1.85)), but not with longer follow-up. The estimated excess mortality
      was greater in women and in patients aged <=70 years at diagnosis. CONCLUSIONS:
      In this large population-based study of biopsy-proven GCA from southern Sweden,
      the incidence of GCA may have decreased over time. Short-term mortality was
      increased, in particular among those diagnosed at <=70 years of age, but long
      term survival was not impaired.

PMID- 24442880
TI  - Leri's pleonosteosis, a congenital rheumatic disease, results from
      microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into
      systemic sclerosis pathogenesis.
AB  - OBJECTIVES: Leri's pleonosteosis (LP) is an autosomal dominant rheumatic
      condition characterised by flexion contractures of the interphalangeal joints,
      limited motion of multiple joints, and short broad metacarpals, metatarsals and
      phalanges. Scleroderma-like skin thickening can be seen in some individuals with
      LP. We undertook a study to characterise the phenotype of LP and identify its
      genetic basis. METHODS AND RESULTS: Whole-genome single-nucleotide polymorphism
      genotyping in two families with LP defined microduplications of chromosome 8q22.1
      as the cause of this condition. Expression analysis of dermal fibroblasts from
      affected individuals showed overexpression of two genes, GDF6 and SDC2, within
      the duplicated region, leading to dysregulation of genes that encode proteins of
      the extracellular matrix and downstream players in the transforming growth factor
      (TGF)-beta pathway. Western blot analysis revealed markedly decreased inhibitory
      SMAD6 levels in patients with LP. Furthermore, in a cohort of 330 systemic
      sclerosis cases, we show that the minor allele of a missense SDC2 variant,
      p.Ser71Thr, could confer protection against disease (p<1*10(-5)). CONCLUSIONS:
      Our work identifies the genetic cause of LP in these two families, demonstrates
      the phenotypic range of the condition, implicates dysregulation of extracellular
      matrix homoeostasis genes in its pathogenesis, and highlights the link between
      TGF-beta/SMAD signalling, growth/differentiation factor 6 and syndecan-2. We
      propose that LP is an additional member of the growing 'TGF-beta-pathies' group
      of musculoskeletal disorders, which includes Myhre syndrome, acromicric
      dysplasia, geleophysic dysplasias, Weill-Marchesani syndromes and stiff skin
      syndrome. Identification of a systemic sclerosis-protective SDC2 variant lays the
      foundation for exploration of the role of syndecan-2 in systemic sclerosis in the
      future.

PMID- 24442882
TI  - The influence of inflammation in the development of subclinical atherosclerosis
      in psoriatic arthritis: comment on 'Cardiovascular comorbidities in patients with
      psoriatic arthritis: a systematic review' by Jamnistki et al.

PMID- 24442883
TI  - Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and
      patient indexes (ESSPRI).
AB  - OBJECTIVES: To validate the two recently developed disease activity indexes for
      assessment of primary Sjogren's syndrome (SS): the European League Against
      Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease
      Activity Index (ESSDAI). METHODS: A prospective international 6-month duration
      validation study was conducted in 15 countries. At each visit, physicians
      completed ESSDAI, SS disease activity index (SSDAI), Sjogren's Systemic Clinical
      Activity Index (SCAI) and physician global assessment (PhGA); and patients
      completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and
      Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties
      (construct validity, responsiveness and reliability) were evaluated and compared
      between scores. RESULTS: Of the 395 patients included, 145 (37%) and 251 (64%)
      had currently active or current or past systemic manifestations, respectively.
      EULAR scores had higher correlation with the gold standard than other scores
      (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient
      and systemic scores were very low (ranging from 0.07 to 0.29). All systemic
      scores had similar large responsiveness in improved patients. Responsiveness of
      patient scores was low but was significantly higher for ESSPRI compared with SSI
      and PROFAD. Reliability was very good for all scores. CONCLUSIONS: ESSDAI and
      ESSPRI had good construct validity. All scores were reliable. Systemic scores had
      a large sensitivity to change in patients whose disease activity improves.
      Patient scores had a small sensitivity to change, however, significantly better
      for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they
      are 2 complementary components that should be both evaluated, but separately.

PMID- 24442884
TI  - Rituximab versus an alternative TNF inhibitor in patients with rheumatoid
      arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a
      global, observational, comparative effectiveness study.
AB  - OBJECTIVES: To compare the effectiveness of rituximab versus an alternative
      tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid
      arthritis (RA) with an inadequate response to one previous TNFi. METHODS: SWITCH
      RA was a prospective, global, observational, real-life study. Patients non
      responsive or intolerant to a single TNFi were enrolled <=4 weeks after starting
      rituximab or a second TNFi. Primary end point: change in Disease Activity Score
      in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte
      sedimentation rate (ESR) over 6 months. RESULTS: 604 patients received rituximab,
      and 507 an alternative TNFi as second biological therapy. Reasons for
      discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and
      other (n=21). A total of 728 patients were available for primary end point
      analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher
      in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least
      squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in
      rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference
      remained significant among patients discontinuing the initial TNFi because of
      inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894).
      Seropositive patients showed significantly greater improvements in DAS28-3-ESR
      with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly
      those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The
      overall incidence of adverse events was similar between the rituximab and TNFi
      groups. CONCLUSIONS: These real-life data indicate that, after discontinuation of
      an initial TNFi, switching to rituximab is associated with significantly improved
      clinical effectiveness compared with switching to a second TNFi. This difference
      was particularly evident in seropositive patients and in those switched because
      of inefficacy.

PMID- 24442885
TI  - Effects and safety of rituximab in systemic sclerosis: an analysis from the
      European Scleroderma Trial and Research (EUSTAR) group.
AB  - OBJECTIVES: To assess the effects of Rituximab (RTX) on skin and lung fibrosis in
      patients with systemic sclerosis (SSc) belonging to the European Scleroderma
      Trial and Research (EUSTAR) cohort and using a nested case-control design.
      METHODS: Inclusion criteria were fulfilment of American College of Rheumatology
      classification criteria for SSc, treatment with RTX and availability of follow-up
      data. RTX-treated patients were matched with control patients from the EUSTAR
      database not treated with RTX. Matching parameters for skin/lung fibrosis were
      the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up
      duration, scleroderma subtype, disease duration and immunosuppressive co
      treatment. The primary analysis was mRSS change from baseline to follow-up in the
      RTX group compared with the control group. Secondary analyses included change of
      FVC and safety measures. RESULTS: 63 patients treated with RTX were included in
      the analysis. The case-control analysis in patients with severe diffuse SSc
      showed that mRSS changes were larger in the RTX group versus matched controls
      (N=25; -24.0+/-5.2% vs -7.7+/-4.3%; p=0.03). Moreover, in RTX-treated patients,
      the mean mRSS was significantly reduced at follow-up compared with baseline
      (26.6+/-1.4 vs 20.3+/-1.8; p=0.0001). In addition, in patients with interstitial
      lung disease, RTX prevented significantly the further decline of FVC compared
      with matched controls (N=9; 0.4+/-4.4% vs -7.7+/-3.6%; p=0.02). Safety measures
      showed a good profile consistent with previous studies in autoimmune rheumatic
      diseases. CONCLUSIONS: The comparison of RTX treated versus untreated matched
      control SSc patients from the EUSTAR cohort demonstrated improvement of skin
      fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic
      concept of B cell inhibition in SSc.

PMID- 24442886
TI  - Zoledronate for prevention of bone erosion in tophaceous gout: a randomised,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVES: The osteoclast has been implicated in development of bone erosion in
      gout. The aim of this study was to determine whether zoledronate, a potent
      antiosteoclast drug, influences bone erosion in people with tophaceous gout.
      METHODS: This was a 2-year, randomised, double-blind, placebo-controlled trial of
      100 people with tophaceous gout. Participants were randomised to annual
      administration of 5 mg intravenous zoledronate or placebo. The primary endpoint
      was change in the foot CT bone erosion score from baseline. Secondary endpoint
      was change in plain radiographic damage scores. Other endpoints were change in
      bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core
      domains for chronic gout studies. RESULTS: There was no change in CT erosion
      scores over 2 years, and no difference between the two treatment groups at Year 1
      or 2 (p(treat)=0.10, p(time)=0.47, p(treat*time)=0.23). Similarly, there was no
      change in plain radiographic scores over 2 years, and no difference between the
      two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of
      femur, total hip and total body BMD. Zoledronate therapy also reduced the bone
      turnover markers P1NP and beta-CTX compared with placebo. There was no difference
      between treatment groups in OMERACT-endorsed core domains. CONCLUSIONS: Despite
      improvements in BMD and suppression of bone turnover markers, antiosteoclast
      therapy with zoledronate did not influence bone erosion in people with tophaceous
      gout. These findings suggest a disconnect between responses in the healthy
      skeleton and at sites of focal bone erosion in tophaceous gout.

PMID- 24442888
TI  - Paracentral scotoma in glaucoma detected by 10-2 but not by 24-2 perimetry.
AB  - PURPOSE: To describe, in glaucomatous patients, spectral-domain optical coherence
      tomography (SD-OCT) results predictive of paracentral visual field (VF) defects
      present on standard automated perimetry (SAP) 10-2, but not on SAP 24-2. METHODS:
      The SAP 10-2 test was repeated 3 times to determine whether paracentral VF
      defects were present. SpectralisTM HRA + OCT was used to obtain speckle-noise
      reduced macular B-scans. The macular scan protocol consisted of 19 vertical cross
      sectional scan lines centered on the fovea (30 degrees  * 15 degrees  volume
      scan), each of which was the average of 50 scans. A 3D OCT-2000 was also used to
      determine macular layer thicknesses and to detect abnormally thin regions (below
      the 1 % confidence interval of the normative data). RESULTS: We identified 3
      cases in which paracentral VF defects were detected on SAP 10-2, but not on SAP
      24-2. Paracentral VF defects were detected on all of the SAP 10-2 tests repeated
      3 times, and included absolute scotoma in 2 of the 3 SAP 10-2 results. Retinal
      nerve fiber layer (RNFL) and ganglion cell layer (GCL) damage was diminished on
      SD-OCT macular images; 2 patients had RNFL and GCL thinning within and central to
      the parafoveal region, where the GCL is generally thickest in healthy eyes, and 1
      patient had evident RNFL and GCL thinning in the papillomacular bundle.
      CONCLUSIONS: Macular SD-OCT scans may be useful in deciding whether SAP 10-2
      should be performed.

PMID- 24442887
TI  - Insights into the binding of GABA to the insect RDL receptor from atomistic
      simulations: a comparison of models.
AB  - The resistance to dieldrin (RDL) receptor is an insect pentameric ligand-gated
      ion channel (pLGIC). It is activated by the neurotransmitter gamma-aminobutyric
      acid (GABA) binding to its extracellular domain; hence elucidating the atomistic
      details of this interaction is important for understanding how the RDL receptor
      functions. As no high resolution structures are currently available, we built
      homology models of the extracellular domain of the RDL receptor using different
      templates, including the widely used acetylcholine binding protein and two
      pLGICs, the Erwinia Chrysanthemi ligand-gated ion channel (ELIC) and the more
      recently resolved GluCl. We then docked GABA into the selected three dimensional
      structures, which we used as starting points for classical molecular dynamics
      simulations. This allowed us to analyze in detail the behavior of GABA in the
      binding sites, including the hydrogen bond and cation-pi interaction networks it
      formed, the conformers it visited and the possible role of water molecules in
      mediating the interactions; we also estimated the binding free energies. The
      models were all stable and showed common features, including interactions
      consistent with experimental data and similar to other pLGICs; differences could
      be attributed to the quality of the models, which increases with increasing
      sequence identity, and the use of a pLGIC template. We supplemented the molecular
      dynamics information with metadynamics, a rare event method, by exploring the
      free energy landscape of GABA binding to the RDL receptor. Overall, we show that
      the GluCl template provided the best models. GABA forming direct salt-bridges
      with Arg211 and Glu204, and cation-pi interactions with an aromatic cage
      including Tyr109, Phe206 and Tyr254, represents a favorable binding arrangement,
      and the interaction with Glu204 can also be mediated by a water molecule. 

PMID- 24442889
TI  - Computer-aided diagnosis system outperforms scoring analysis in myocardial
      perfusion imaging.
AB  - BACKGROUND: The aim of this myocardial perfusion imaging (MPI) study was to
      compare the diagnostic performance of two computer-aided diagnosis (CAD) systems,
      EXINI Heart(TM) (EXINI), and PERFEX(TM) (PERFEX) Emory Cardiac Toolbox (ECT), and
      the summed stress score (SSS) values from both software packages. METHODS: We
      studied 1,052 consecutive patients who underwent 2-day stress/rest (99m)Tc
      sestamibi MPI studies. The reference standard classifications for the MPI studies
      were obtained from three experienced physicians who separately classified all
      cases regarding the presence or absence of ischemia and/or infarction. Automatic
      processing was carried out using EXINI and PERFEX to obtain CAD results and SSS
      values based on the 17-segment model. RESULTS: The three experts' classifications
      showed ischemia in 257 patients and abnormal studies, i.e., either ischemia or
      infarction or both, in 318 patients. Accuracy was significantly higher in EXINI
      than in PERFEX, regarding both the detection of ischemia (87.4 vs 77.6%; P <
      0.0001) and the detection of abnormal studies (91.6 vs 67.9%; P < 0.0001).
      EXINI's CAD system showed a higher specificity than its SSS values (86.8 vs
      73.6%; P < 0.0001) at the same level of sensitivity. CONCLUSIONS: EXINI
      demonstrated greater diagnostic accuracy for detection of ischemia and abnormal
      studies than did PERFEX. EXINI CAD also outperformed its SSS analysis.

PMID- 24442890
TI  - A genomewide overexpression screen identifies genes involved in the
      phosphatidylinositol 3-kinase pathway in the human protozoan parasite Entamoeba
      histolytica.
AB  - Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and
      liver abscess. E. histolytica relies on motility, phagocytosis, host cell
      adhesion, and proteolysis of extracellular matrix for virulence. In eukaryotic
      cells, these processes are mediated in part by phosphatidylinositol 3-kinase
      (PI3K) signaling. Thus, PI3K may be critical for virulence. We utilized a
      functional genomics approach to identify genes whose products may operate in the
      PI3K pathway in E. histolytica. We treated a population of trophozoites that were
      overexpressing genes from a cDNA library with a near-lethal dose of the PI3K
      inhibitor wortmannin. This screen was based on the rationale that survivors would
      be overexpressing gene products that directly or indirectly function in the PI3K
      pathway. We sequenced the overexpressed genes in survivors and identified a cDNA
      encoding a Rap GTPase, a protein previously shown to participate in the PI3K
      pathway. This supports the validity of our approach. Genes encoding a coactosin
      like protein, EhCoactosin, and a serine-rich E. histolytica protein (SREHP) were
      also identified. Cells overexpressing EhCoactosin or SREHP were also less
      sensitive to a second PI3K inhibitor, LY294002. This corroborates the link
      between these proteins and PI3K. Finally, a mutant cell line with an increased
      level of phosphatidylinositol (3,4,5)-triphosphate, the product of PI3K activity,
      exhibited increased expression of SREHP and EhCoactosin. This further supports
      the functional connection between these proteins and PI3K in E. histolytica. To
      our knowledge, this is the first forward-genetics screen adapted to reveal genes
      participating in a signal transduction pathway in this pathogen. 

PMID- 24442891
TI  - pH signaling in human fungal pathogens: a new target for antifungal strategies.
AB  - Fungi are exposed to broadly fluctuating environmental conditions, to which
      adaptation is crucial for their survival. An ability to respond to a wide pH
      range, in particular, allows them to cope with rapid changes in their
      extracellular settings. PacC/Rim signaling elicits the primary pH response in
      both model and pathogenic fungi and has been studied in multiple fungal species.
      In the predominant human pathogenic fungi, namely, Candida albicans, Aspergillus
      fumigatus, and Cryptococcus neoformans, this pathway is required for many
      functions associated with pathogenesis and virulence. Aspects of this pathway are
      fungus specific and do not exist in mammalian cells. In this review, we highlight
      recent advances in our understanding of PacC/Rim-mediated functions and discuss
      the growing interest in this cascade and its factors as potential drug targets
      for antifungal strategies. We focus on both conserved and distinctive features in
      model and pathogenic fungi, highlighting the specificities of PacC/Rim signaling
      in C. albicans, A. fumigatus, and C. neoformans. We consider the role of this
      pathway in fungal virulence, including modulation of the host immune response.
      Finally, as now recognized for other signaling cascades, we highlight the role of
      pH in adaptation to antifungal drug pressure. By acting on the PacC/Rim pathway,
      it may therefore be possible (i) to ensure fungal specificity and to limit the
      side effects of drugs, (ii) to ensure broad-spectrum efficacy, (iii) to attenuate
      fungal virulence, (iv) to obtain additive or synergistic effects with existing
      antifungal drugs through tolerance inhibition, and (v) to slow the emergence of
      resistant mutants. 

PMID- 24442892
TI  - Calcineurin controls hyphal growth, virulence, and drug tolerance of Candida
      tropicalis.
AB  - Candida tropicalis, a species closely related to Candida albicans, is an emerging
      fungal pathogen associated with high mortality rates of 40 to 70%. Like C.
      albicans and Candida dubliniensis, C. tropicalis is able to form germ tubes,
      pseudohyphae, and hyphae, but the genes involved in hyphal growth machinery and
      virulence remain unclear in C. tropicalis. Recently, echinocandin- and azole
      resistant C. tropicalis isolates have frequently been isolated from various
      patients around the world, making treatment difficult. However, studies of the C.
      tropicalis genes involved in drug tolerance are limited. Here, we investigated
      the roles of calcineurin and its potential target, Crz1, for core stress
      responses and pathogenesis in C. tropicalis. We demonstrate that calcineurin and
      Crz1 are required for hyphal growth, micafungin tolerance, and virulence in a
      murine systemic infection model, while calcineurin but not Crz1 is essential for
      tolerance of azoles, caspofungin, anidulafungin, and cell wall-perturbing agents,
      suggesting that calcineurin has both Crz1-dependent and -independent functions in
      C. tropicalis. In addition, we found that calcineurin and Crz1 have opposite
      roles in controlling calcium tolerance. Calcineurin serves as a negative
      regulator, while Crz1 plays a positive role for calcium tolerance in C.
      tropicalis. 

PMID- 24442894
TI  - Psychopathy: what apology making tells us about moral agency.
AB  - Psychopathy is often used to settle disputes about the nature of moral judgment.
      The "trolley problem" is a familiar scenario in which psychopathy is used as a
      test case. Where a convergence in response to the trolley problem is registered
      between psychopathic subjects and non-psychopathic (normal) subjects, it is
      assumed that this convergence indicates that the capacity for making moral
      judgments is unimpaired in psychopathy. This, in turn, is taken to have
      implications for the dispute between motivation internalists and motivation
      externalists, for instance. In what follows, we want to do two things: firstly,
      we set out to question the assumption that convergence is informative of the
      capacity for moral judgment in psychopathy. Next, we consider a distinct feature
      of psychopathy which we think provides strong grounds for holding that the
      capacity for moral judgment is seriously impaired in psychopathic subjects. The
      feature in question is the psychopathic subject's inability to make sincere
      apologies. Our central claim will be this: convergence in response to trolley
      problems does not tell us very much about the psychopathic subject's capacity to
      make moral judgments, but his inability to make sincere apologies does provide us
      with strong grounds for holding that this capacity is seriously impaired in
      psychopathy. 

PMID- 24442893
TI  - High-throughput chemical screening for antivirulence developmental phenotypes in
      Trypanosoma brucei.
AB  - In the bloodstream of mammalian hosts, the sleeping sickness parasite,
      Trypanosoma brucei, exists as a proliferative slender form or a nonproliferative,
      transmissible, stumpy form. The transition between these developmental forms is
      controlled by a density-dependent mechanism that is important for the parasite's
      infection dynamics, immune evasion via ordered antigenic variation, and disease
      transmissibility. However, stumpy formation has been lost in most laboratory
      adapted trypanosome lines, generating monomorphic parasites that proliferate
      uncontrolled as slender forms in vitro and in vivo. Nonetheless, these forms are
      readily amenable to cell culture and high-throughput screening for trypanocidal
      lead compounds. Here, we have developed and exploited a high-throughput screen
      for developmental phenotypes using a transgenic monomorphic cell line expressing
      a reporter under the regulation of gene control signals from the stumpy-specific
      molecule PAD1. Using a whole-cell fluorescence-based assay to screen over 6,000
      small molecules from a kinase-focused compound library, small molecules able to
      activate stumpy-specific gene expression and proliferation arrest were assayed in
      a rapid assay format. Independent follow-up validation identified one hit able to
      induce modest, yet specific, changes in mRNA expression indicative of a partial
      differentiation to stumpy forms in monomorphs. Further, in pleomorphs this
      compound induced a stumpy-like phenotype, entailing growth arrest, morphological
      changes, PAD1 expression, and enhanced differentiation to procyclic forms. This
      not only provides a potential tool compound for the further understanding of
      stumpy formation but also demonstrates the use of high-throughput screening in
      the identification of compounds able to induce specific phenotypes, such as
      differentiation, in African trypanosomes. 

PMID- 24442895
TI  - Erratum to the art and angst of the mentoring relationship.

PMID- 24442896
TI  - Teaching and supervising psychotherapy: opening statement.

PMID- 24442897
TI  - Postgraduate psychotherapy training : incorporating findings from the empirical
      literature into curriculum development.
AB  - This article presents a postgraduate psychotherapy training curriculum that
      incorporates findings from the psychotherapy research literature. Prior training
      recommendations are reviewed, and selected references from the empirical
      literature form the basis of the discussion. Past guidelines have not always
      incorporated findings from this literature. A curriculum is presented as a first
      step toward making this connection. This curriculum was implemented at McMaster
      University, Hamilton, Ontario, in the summer of 1995. The psychotherapy research
      literature can assist psychotherapy coordinators to design curricula that are
      challenging and that can provide the necessary skills future psychiatrists will
      need. 

PMID- 24442898
TI  - Liabifity and accountability in psychotherapy supervision : a review, survey, and
      proposal.
AB  - The contemporary climate of medical-legal liability, and of increasing
      expectations of accountability from agencies that pay for psychiatric services
      and training stipends, has created an atmosphere within which issues of liability
      and accountability should be constructively addressed. The authors conducted a
      nationwide survey of psychiatry residency training directors and asked them to
      estimate the awareness of their supervisors of liability issues pertinent to the
      supervision of psychiatric residents learning psychotherapy. While the training
      directors assume that their faculty supervisors, including volunteer faculty, are
      familiar with issues of accountability, very few make tangible efforts to provide
      this information. The authors found that patients are not routinely informed of
      the identity of supervisors, although the patients are usually informed that a
      therapist is in training. The authors propose practical interventions whereby
      residency training programs could address the issues of faculty members'
      awareness of their accountability, the education and training of supervisors, the
      documentation of supervisory sessions, and the attitudes and practices of
      psychotherapy trainees. 

PMID- 24442899
TI  - Psychotherapy supervision : a current method.
AB  - Psychotherapy supervision remains a crucial element in psychiatric residency
      training. The rapidly changing health care system is forcing supervisors to
      explore new methods of psychotherapy training. Supervisors must contend with
      decreased time for supervision, increased numbers of patients per resident, and
      patient cases that turn over more quickly. All of these changes require a more
      efficient and effective method of psychotherapy supervision. The authors propose
      a method that provides the psychiatry resident two supervisors for the price of
      one, that is, the psychotherapy supervisor and the resident himself or herself
      The authors detail the use of this method and present its potential advantages
      and difficulties. 

PMID- 24442900
TI  - Teaching psychodynamic technique during an observed analytic psychotherapy
      interview.
AB  - Psychodynamic techniques of confrontation, clarification, and interpretation were
      taught to psychiatry residents during "live" analytic psychotherapy interviews.
      First, during a therapeutic interview with a resident's patient in a seminar
      group setting, the interviewer (author) periodically stopped to discuss
      formulations and technique. Later, the author conducted the interviews until
      dynamic intervention seemed indicated; at those points, the author stopped,
      discussed the defenses and affects causing pathology, and then asked a resident
      to make the psychodynamic intervention with the patient. This teaching technique
      was rated by the residents as extremely helpful in integrating psychoanalytic
      theory with clinical interventions. 

PMID- 24442902
TI  - Interviewing the black elderly at home.

PMID- 24442901
TI  - Collaboration with the nonphysician therapist : a seminar for postgraduate third
      year psychiatry residents.
AB  - The integration of psychotherapy and pharmacotherapy becomes more complex when
      two clinicians collaborate in providing patient treatment. A course for
      postgraduate third-year psychiatry residents was developed to review the
      literature, discuss various treatment models, and delineate the technical skills
      and treatment issues involved in the collaborative model. This article describes
      the course content, design, and evaluation at one institution. 

PMID- 24442903
TI  - Residency education: teaching about maintenance and violation of boundaries.

PMID- 24442904
TI  - In reply.

PMID- 24442907
TI  - Multispectroscopic studies on the interaction of a platinum(II) complex
      containing L-histidine and 1,10-phenanthroline ligands with bovine serum albumin.
AB  - The mechanism of the interaction between bovine serum albumin (BSA) and [Pt(phen)
      (histidine)](+) complex was studied employing ultraviolet (UV) absorption,
      circular dichroism (CD), FT-IR, differential pulse voltammetry (DPV), and
      fluorescence spectral methods. Fluorescence data showed that the intrinsic
      fluorescence of BSA was strongly quenched by Pt(II) complex in terms of an
      untypical static quenching process. The corresponding number of binding sites (n)
      and binding constant (K b) of BSA and complex at 283, 298, and 310 K were
      calculated to be 0.61 * 10(6), 19 * 10(6), and 42 * 10(6) M(-1), respectively.
      The results showed that the increasing temperature improves the stability of the
      complex-BSA system, which results in a higher binding constant and the number of
      binding sites of the complex-BSA system. The positive DeltaH and positive DeltaS
      indicated that hydrophobic forces might play a major role in the binding between
      complex and BSA. Based on Forster's theory of non-radiation energy transfer, the
      binding distance (r) between the donor (BSA) and acceptor (Pt(II) complex) was
      evaluated. The results of CD, UV-vis, DPV, and FT-IR spectroscopy showed that the
      binding of Pt(II) complex to BSA induced conformational changes in BSA.

PMID- 24442908
TI  - Cultural Differences in Personality and Aggressive Behavior in Intimate Partner
      Violence Offenders: A Comparison of English and Spanish Offenders.
AB  - Intimate partner violence (IPV) is a ubiquitous and serious problem, the
      prevalence of which varies greatly around the world. Previous research shows that
      cultural factors interact with personality and that this interaction influences
      cognitions, attitudes, and behaviors that are related to personal and individual
      styles of resolving conflicts. In relation to this, the present study has three
      aims: comparing the self-reported IPV (physical, psychological and sexual) of
      English and Spanish offenders, comparing the Millon Clinical Multiaxial Inventory
      III (MCMI-III) scores of the two groups, and examining the association between
      country of origin, psychopathology, and IPV. The sample consists of 147 IPV
      offenders (80 English and 67 Spanish). The measures used were the MCMI-III and
      the Conflict Tactics Scale 2. The Mann-Whitney U tests were used to compare the
      English and Spanish sample, and independent logistic regressions were used to
      examine the relationship between personality patterns, psychopathology and
      culture, and IPV. Higher frequencies of physical and psychological aggression
      were found in the English group compared with the Spanish group as well as
      several differences in personality patterns and psychopathology between the
      groups. Some MCMI-III subscales also interact with nationality and predict
      physical and psychological aggression. The relevance of these results for
      intervention is discussed.

PMID- 24442909
TI  - A General Strain Approach to Psychological and Physical Bullying: A Study of
      Interpersonal Aggression at School.
AB  - Although studies have been conducted to examine the applicability of Agnew's
      general strain theory (GST) to the explanation of school bullying, GST research
      on the phenomenon remains limited in number and scope. To fill this gap in
      research, using data from a sample of 296 middle school students in a
      southwestern state of the United States, this article examined whether different
      types of strain and negative emotions are positively associated with
      psychological, physical, and general bullying. Overall findings of negative
      binomial regression analyses tended to be consistent with our expectations, while
      some aspects of GST received more empirical support than others. Strains and
      negative emotions were mostly related positively either to psychological or
      physical bullying, with negative emotions, anger and depression, partly mediating
      the strain-bullying relationship. However, we found mixed patterns of
      interactions among strains, negative emotions, and conditioning factors.
      Theoretical and practical implications were discussed.

PMID- 24442910
TI  - Predicting Treatment Attrition Among Seriously Violent Offenders: An Application
      of the Directionality Model.
AB  - Treatment completion by violent offenders results in fewer victims and less
      violence in society. As researchers and members of society, we have a compelling
      interest in finding ways to keep violent male offenders in effective treatment
      programs. This study examines file-rated predictors of treatment attrition from
      an institutionally based program for persistently violent offenders. Each of the
      three prediction models of institutionally based treatment attrition included the
      predictors of motivation for assistance and prior treatment dosage: (a) the past
      criminal behavior model, (b) the recent antisocial behavior model, and (c) the
      non-antisocial instability model. Recent antisocial behavior did not improve the
      prediction of treatment attrition over the past criminal behavior model.
      Motivation for assistance did not make a contribution in the recent antisocial
      behavior or the non-antisocial instability models while prior treatment dosage
      consistently contributed to the prediction of attrition across the models. Recent
      non-antisocial behavior is important to offender treatment attrition.

PMID- 24442911
TI  - Criminal Recidivism Among Homicide Offenders.
AB  - Homicide offenders are released to communities in large numbers. Little is known,
      however, about how these offenders fare after release. The aim of this study is
      threefold: to examine recidivism patterns among released homicide offenders, to
      assess to what extent predictors for recidivism are similar to those for other
      violent offenders, and to study whether the degree of recidivism differs by type
      of homicide. Using data from the Pennsylvania Department of Corrections, we
      extracted all individuals who committed a homicide in Philadelphia between 1977
      and 1983 and who were paroled. Data were supplemented with court documents,
      police department data, and newspaper articles. We examined frequency and
      severity of recidivism, and used logistic regression analyses and survival
      analyses to examine the likelihood and time to recidivism. Of the 92 paroled
      homicide offenders, 54% recidivated; 15% recidivated with a violent offense. Race
      and original conviction for a financially motivated homicide were significant
      predictors of recidivism. While socio-demographic predictors of recidivism have
      theoretical and practical significance, focusing on factors associated with the
      motive of the original homicide may prove highly beneficial for intervention
      strategies and post-release planning.

PMID- 24442912
TI  - Making sense of denial in sexual offenders: a qualitative phenomenological and
      repertory grid analysis.
AB  - Denial in sexual offenders represents the first barrier to successful treatment a
      clinician is likely to face. Most sex offender treatment programs devote
      significant time to overcoming denial, with most programs having a focus on
      disclosure and "accepting responsibility." This is the first study that has aimed
      to make sense of sexual offenders' denial through a rigorous qualitative
      analysis. The main objective was to explore the experiences and lived worlds of
      sexual offenders in denial. A qualitative phenomenological methodology combining
      interpretative phenomenological analysis and repertory grids was implemented. Ten
      incarcerated sexual offenders in categorical denial participated in the research.
      The analysis revealed the narrative, relational, and self-reconstructive
      properties of denial and discusses the role and function denial may be playing
      for sexual offenders. The results highlight that denial can be viewed as a form
      of "sense making" and that clinically relevant treatment targets can be elicited
      without disclosure. It is concluded that viewing denial as a barrier to treatment
      impedes constructive work with offenders, and implications for treatment are
      discussed. 

PMID- 24442913
TI  - PHOX2B polyalanine repeat length is associated with sudden infant death syndrome
      and unclassified sudden infant death in the Dutch population.
AB  - Unclassified sudden infant death (USID) is the sudden and unexpected death of an
      infant that remains unexplained after thorough case investigation including
      performance of a complete autopsy and review of the circumstances of death and
      the clinical history. When the infant is below 1 year of age and with onset of
      the fatal episode apparently occurring during sleep, this is referred to as
      sudden infant death syndrome (SIDS). USID and SIDS remain poorly understood
      despite the identification of several environmental and some genetic risk
      factors. In this study, we investigated genetic risk factors involved in the
      autonomous nervous system in 195 Dutch USID/SIDS cases and 846 Dutch, age-matched
      healthy controls. Twenty-five DNA variants from 11 genes previously implicated in
      the serotonin household or in the congenital central hypoventilation syndrome, of
      which some have been associated with SIDS before, were tested. Of all DNA
      variants considered, only the length variation of the polyalanine repeat in exon
      3 of the PHOX2B gene was found to be statistically significantly associated with
      USID/SIDS in the Dutch population after multiple test correction. Interestingly,
      our data suggest that contraction of the PHOX2B exon 3 polyalanine repeat that we
      found in six of 160 SIDS and USID cases and in six of 814 controls serves as a
      probable genetic risk factor for USID/SIDS at least in the Dutch population.
      Future studies are needed to confirm this finding and to understand the
      functional effect of the polyalanine repeat length variation, in particular
      contraction, in exon 3 of the PHOX2B gene.

PMID- 24442914
TI  - A pilot validation study for the NOX T3(TM) portable monitor for the detection of
      OSA.
AB  - PURPOSE: The aim of the current pilot study is to compare the diagnostic accuracy
      of the NOX T3(TM) (T3) portable sleep monitor (PM) to that of simultaneously
      recorded in-lab polysomnogram (PSG). METHODS: A total of 40 participants were
      recruited following face-to-face evaluation at a sleep disorders clinic. Each
      participant wore both PSG and PM equipment simultaneously during their in-lab
      PSG. PSG records were manually scored using the American Academy of Sleep
      Medicine (AASM) criteria, and PM records were double-scored using the device's
      autoscore algorithm as well as manual scoring. RESULTS: The final sample
      consisted of 32 participants (56% male, 50% black) with a mean ESS, BMI, and
      apnea-hypopnea index (AHI) of 10.4, 32.8, and 16.3, respectively. Three
      participants (7.5%) were excluded for poor PM signal quality. Mean AHI derived
      from the T3's autoscore algorithm was similar to that from manual scoring (19.6
      +/- 18.9 vs. 18.6 +/- 19.1, respectively). Autoscore-derived T3 AHI and PSG
      derived AHI were strongly related (r = .93). The T3 (autoscored AHI) demonstrated
      a high degree of sensitivity for the presence of obstructive sleep apnea syndrome
      (OSA; 100%) and acceptable specificity for the exclusion of OSA using an AHI
      cutoff of >=5 events/h (70%). The unit (autoscored) had a high degree of both
      sensitivity (92%) and specificity (85%) when the presence of OSA was defined more
      conservatively (AHI > 15 events/h). For OSA defined as an AHI of >=5, the T3
      (autoscored) correctly identified 88% of positive cases and 100% of negative
      cases. CONCLUSIONS: In this small, clinic-based sample, the T3 demonstrated very
      good measurement agreement compared to PSG and a high degree of sensitivity for
      detecting even mild OSA. False positives appeared to be due to respiratory effort
      related arousals (RERAs) being autoscored as obstructive apneas and may be due to
      inherent discrepancy in flow measurement sensitivity between PSG and portable
      monitors.

PMID- 24442915
TI  - Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: a
      combined chemical and computational study.
AB  - Three forms of lactoferrin (Lf) that differed in their levels of iron loading
      (Lf, LfFe, and LfFe2) were simultaneously labeled with the fluorophores AF350 and
      AF430. All three resulting fluorescent lactoferrins exhibited fluorescence
      resonance energy transfer (FRET), but they all presented different FRET patterns.
      Whereas only partial FRET was observed for Lf and LfFe, practically complete FRET
      was seen for the holo form (LfFe2). For each form of metal-loaded lactoferrin,
      the AF350-AF430 distance varied depending on the protein conformation, which in
      turn depended on the level of iron loading. Thus, the FRET patterns of these
      lactoferrins were found to correlate with their iron loading levels. In order to
      gain greater insight into the number of fluorophores and the different FRET
      patterns observed (i.e., their iron levels), a computational analysis was
      performed. The results highlighted a number of lysines that have the greatest
      influence on the FRET profile. Moreover, despite the lack of an X-ray structure
      for any LfFe species, our study also showed that this species presents modified
      subdomain organization of the N-lobe, which narrows its iron-binding site.
      Complete domain rearrangement occurs during the LfFe to LfFe2 transition.
      Finally, as an example of the possible applications of the results of this study,
      we made use of the FRET fingerprints of these fluorescent lactoferrins to monitor
      the interaction of lactoferrin with a healthy bacterium, namely Bifidobacterium
      breve. This latter study demonstrated that lactoferrin supplies iron to this
      bacterium, and suggested that this process occurs with no protein
      internalization. 

PMID- 24442917
TI  - Helminth therapy (worms) for induction of remission in inflammatory bowel
      disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, globally-occurring
      gastrointestinal disorder and a major cause of illness and disability. It is
      conventionally classified into Crohn's disease (CD) and ulcerative colitis (UC).
      Helminths are parasitic worms with complex life cycles involving tissue- or lumen
      dwelling stages in their hosts, and causing long-lasting or chronic infections
      that are frequently asymptomatic. Helminths modulate immune responses of their
      hosts, and many observational and experimental studies support the hypothesis
      that helminths suppress immune-mediated chronic inflammation that occurs in
      asthma, allergy and IBD. OBJECTIVES: The objective was to evaluate the efficacy
      and safety of helminth treatment for induction of remission in IBD. SEARCH
      METHODS: We searched the following databases from inception to 13 July 2013:
      MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the
      Cochrane Inflammatory Bowel Disease Group Specialized Trials Register. We also
      searched four online trials registries, and abstracts from major meetings. There
      were no language restrictions. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) where the intervention was any helminth species or combination of helminth
      species, administered in any dose and by any route and for any duration of
      exposure to people with active CD or UC, confirmed through any combination of
      clinical, endoscopic and histological criteria were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      eligibility using a standardized data collection form. We used the RevMan
      software for analyses. The primary outcome was induction of remission as defined
      by the included studies. Secondary outcomes included clinical, histologic, or
      endoscopic improvement as defined by the authors, endoscopic mucosal healing,
      change in disease activity index score, change in quality of life score, hospital
      admissions, requirement for intravenous corticosteroids, surgery, study
      withdrawal and the incidence of adverse events. We calculated the risk ratio (RR)
      and corresponding 95% confidence interval (CI) for dichotomous outcomes. We
      calculated the mean difference (MD) and 95% CI for continuous outcomes. We
      assessed the methodological quality of included studies using the Cochrane risk
      of bias tool. The overall quality of the evidence supporting each outcome was
      assessed using the GRADE criteria. MAIN RESULTS: Two RCTs (90 participants) were
      included. One trial assessed the efficacy and safety of Trichuris suis (T. suis)
      ova in patients with UC (n = 54). The other RCT was a phase one that assessed the
      safety and tolerability of T. suis ova in patients with CD (n = 36). The risk of
      bias in both studies was judged to be low. In the UC study, during the 12-week
      study period, participants in the active arm received 2-weekly aliquots of 2500
      T. suis eggs, added to 0.8 mL of saline; those in the placebo arm received 0.8 mL
      saline only. There were sparse data available for the outcomes clinical remission
      and clinical improvement. Ten per cent (3/30) of patients in the T. suis arm
      entered remission compared to 4% (1/24) of patients in the placebo arm (RR 2.40,
      95% CI 0.27 to 21.63). Forty-three per cent (13/30) of patients in the T. suis
      group achieved clinical improvement compared to 17% (4/24) of placebo patients
      (RR 2.60, 95% CI 0.97 to 6.95). The mean ulcerative colitis disease activity
      index (UCDAI) score was lower in the T. suis group (6.1 +/- 0.61) compared to the
      placebo group (7.5 +/- 0.66) after 12 weeks of treatment (MD -1.40, 95% CI -1.75
      to -1.05). There was only limited evidence relating to the proportion of patients
      who experienced an adverse event. Three per cent (1/30) of patients in the T.
      suis group experienced at least one adverse event compared to 12% (3/24) of
      placebo patients (RR 0.27, 95% CI 0.03 to 2.40). None of the adverse events
      reported in this study were judged to be related to the study treatment. GRADE
      analyses rated the overall quality of the evidence for the primary and secondary
      outcomes (i.e. clinical remission and improvement) as low due to serious
      imprecision. In the CD study, participants received a single treatment of T. suis
      ova at a dosage of 500 (n = 9), 2500 (n = 9), or 7500 (n = 9) embryonated eggs or
      matching placebo (n = 9). The CD study did not assess clinical remission or
      improvement as outcomes. There were sparse data on adverse events at two weeks.
      Thirty-seven per cent (10/27) of patients in the T. suis group experienced at
      least one adverse event compared to 44% (4/9) of placebo patients (RR 0.83, 95%
      CI 0.35 to 2.01). Only one adverse event (dysgeusia) was judged to be possibly
      related to treatment in this study. Dysgeusia was reported in one patient in the
      T. suis group and in one patient in the placebo group. AUTHORS' CONCLUSIONS:
      Currently, there is insufficient evidence to allow any firm conclusions regarding
      the efficacy and safety of helminths used to treat patients with IBD. The
      evidence for our primary efficacy outcomes in this review comes from one small
      study and is of low quality due to serious imprecision. We do not have enough
      evidence to determine whether helminths are safe when used in patients with UC
      and CD. Further RCTs are required to assess the efficacy and safety of helminth
      therapy in IBD.

PMID- 24442918
TI  - Energetic aspects of the light activation of two chloroplast enzymes: fructose
      1,6-bisphosphatase and NADP-malate dehydrogenase.
AB  - The light energy requirements for photoactivation of two chloroplast enzymes:
      fructose-1,6-bisphosphatase and NADP-malate dehydrogenase were studied in a
      reconstituted chloroplast system. This system comprised isolated pea thylakoids,
      ferredoxin (Fd), ferredoxin-thioredoxin reductase (FTR) thioredoxinm and f (Tdm,
      Tdf) and the photoactivatable enzyme. Light-saturation curves of the
      photoactivation process were established with once washed thylakoids which did
      not require the addition of Td for light activation. They exhibited a plateau at
      10 W.m(-2) under nitrogen and 50 W.m(-2) under air, while NADP photoreduction was
      saturated at 240 W.m(-2). Cyclic and pseudocyclic phosphorylations saturated at
      identical levels as enzyme photoactivations. All these observations suggested
      that the shift of the light saturation plateau towards higher values under air
      was due to competing oxygen-dependent reactions. With twice washed thylakoids,
      which required Td for enzyme light-activation, photophosphorylation was
      stimulated under N2 by the addition of the components of the photoactivation
      system. Its rate increased with increasing Td concentrations, just as did the
      enzyme photoactivation rate, while varying the target enzyme concentration had
      only a weak effect. Considering that Td concentrations were in a large excess
      over target enzyme concentrations, it may be assumed that the observed ATP
      synthesis was essentially dependent on the rate of Td reduction.Under air, Fd
      dependent pseudo-cyclic photophosphorylation was not stimulated by the addition
      of the other enzyme photoactivation components, suggesting that an important site
      of action of O2 was located at the level of Fd. 

PMID- 24442916
TI  - Methanolic extract of Piper nigrum fruits improves memory impairment by
      decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer's
      disease.
AB  - The present study analyzed the possible memory-enhancing and antioxidant
      proprieties of the methanolic extract of Piper nigrum L. fruits (50 and 100
      mg/kg, orally, for 21 days) in amyloid beta(1-42) rat model of Alzheimer's
      disease. The memory-enhancing effects of the plant extract were studied by means
      of in vivo (Y-maze and radial arm-maze tasks) approaches. Also, the antioxidant
      activity in the hippocampus was assessed using superoxide dismutase-, catalase-,
      glutathione peroxidase-specific activities and the total content of reduced
      glutathione, malondialdehyde, and protein carbonyl levels. The amyloid beta(1-42)
      treated rats exhibited the following: decrease of spontaneous alternations
      percentage within Y-maze task and increase of working memory and reference memory
      errors within radial arm-maze task. Administration of the plant extract
      significantly improved memory performance and exhibited antioxidant potential.
      Our results suggest that the plant extract ameliorates amyloid beta(1-42)-induced
      spatial memory impairment by attenuation of the oxidative stress in the rat
      hippocampus.

PMID- 24442919
TI  - Effects of weather during leaf development on photosynthetic characteristics of
      soybean leaves.
AB  - Net photosynthetic rates and mesophyll conductances at 25  degrees C at light
      saturation and air levels of carbon dioxide and oxygen were measured on recently
      fully expanded leaflets of second trifoliolate leaves of soybeans (Glycine max
      cv. Kent). Plants were grown outdoors in pots at Beltsville, Maryland with 14
      planting times from May through August, 1983. Air temperature and humidity, and
      photosynthetically active radiation (PAR) were measured for the expansion periods
      of the second trifoliolate leaves. Rates of net photosynthesis ranged from 24 to
      33 MUmol m(-2) s(-1), and mesophyll conductances from 0.24 to 0.35 cm s(-1) for
      the different planting dates. Mean 24-h air temperatures ranged from 20.6 to 29.0
      degrees C, and mean daily PAR ranged from 29.4 to 58.4 mol m(-2) d(-1) for the
      leaf expansion periods. There was a positive relationship between photosynthetic
      characteristics and PAR during leaf expansion, and a negative relationship
      between photosynthetic characteristics and leaf expansion rates, with 96% of the
      variation in photosynthetic characteristics accounted for by these two variables.
      Leaf expansion rates were highly correlated with air temperature. 

PMID- 24442921
TI  - Editorial note.

PMID- 24442920
TI  - Effect of light intensity on ammonia assimilation in maize leaves.
AB  - The effect of light on the metabolism of ammonia was studied by subjecting
      detached maize leaves to 150 or 1350 MUmol m(-2) s(-1) PAR during incubation with
      the leaf base in 2 mM (15)NH4Cl. After up to 60 min, leaves were extracted.
      Ammonia, glutamine, glycine, serine, alanine, and aspartate were separated by
      isothermal distillation and ion exchange chromatography. (15)N enrichments were
      analyzed by emission spectroscopy. The uptake of ammonium chloride did not
      influence CO2 assimilation (8.3 and 17.4 MUmol m(-1) s(-1) at 150 and 1350 MUmol
      m(-2) s(-1) PAR, respectively). Leaves kept at high light intensity contained
      more serine and less alanine than leaves from low light treatments. Within 1 h of
      incubation the enrichment of ammonia extracted from leaves rose to approximately
      20% (15)N. In the high light regime the amino acids contained up to 15% (15)N,
      whereas in low light (15)N enrichments were small (up to 6%). The kinetics of
      (15)N incorporation indicated that NH3 was firstly assimilated into glutamine and
      then into glutamate. After 15 min (15)N was also found in glycine, serine and
      alanine. At high light intensity nearly half of the (15)N was incorporated in
      glycine. On the other hand, at low light intensity alanine was the predominant
      (15)N sink. It is concluded that light influences ammonia assimilation at the
      glutamine synthetase reaction. 

PMID- 24442922
TI  - Regulation of photosynthetic electron transport by bicarbonate formate and
      herbicides in isolated broken and intact chloroplasts.
AB  - In this paper, we have presented a minireview on the interaction of bicarbonate,
      formate and herbicides with the thylakoid membranes.The regulation of
      photosynthetic electron transport by bicarbonate, formate and herbicides is
      described. Bicarbonate, formate, and many herbicides act between the primary
      quinone electron acceptor QA and the plastoquinone pool. Many herbicides like the
      ureas, triazines and the phenol-type herbicides act, probably, by the
      displacement of the secondary quinone electron acceptor QB from its binding site
      on a QB-binding protein located at the acceptor side of Photosystem II. Formate
      appears to be an inhibitor of electron transport; this inhibition can be removed
      by the addition of bicarbonate. There appears to be an interaction of the
      herbicides with bicarbonate and/or It has been suggested that both the binding of
      a herbicide and the absence of bicarbonate may cause a conformational alteration
      of the environment of the QB-binding site. The alteration brought about by a
      herbicide decreases the affinity for another herbicide or for bicarbonate; the
      change caused by the absence of bicarbonate decreases the affinity for
      herbicides. Moreover, this change in conformation causes an inhibition of
      electron transport. A bicarbonate-effect in isolated intact chloroplasts is
      demonstrated. 

PMID- 24442923
TI  - Regulation of photosynthetic CO2-pathway enzymes by light and other factors.
AB  - The regulatory properties of enzymes of the pathway of CO2 fixation are discussed
      in relation to changes in regulatory parameters with changing light, CO2 and
      temperature. 

PMID- 24442924
TI  - Consequences of iron deficiency on photosynthetic and respiratory electron
      transport in blue-green algae.
AB  - Growth of Aphanocapsa in low iron media resulted in a decrease of the endogenous
      iron pool. Below a critical concentration photosynthetic electron transfer was
      specifically depressed. This was caused by a strong inhibition of the synthesis
      of cytochromes b-559 of PSII, cytochromes b-563, f-557, and the 'Rieske' Fe-S
      center of the cytochrome complex and especially the Fe-S centers of PSI. The
      influence of iron limitation on respiration and chlorphyll formation was
      negligible. 

PMID- 24442925
TI  - Regulation of photosynthetic carbon assimilation at the cellular level: a review.
AB  - In green leaves and a number of algae, photosynthetically derived carbon is
      ultimately converted into two carbohydrate end-products, sucrose and starch.
      Drainage of carbon from the Calvin cycle proceeds via triose phosphate, fructose
      6-phosphate and glycollate. Gluconeogenesis in photosynthetic cells is controlled
      by light, inorganic phosphate and phosphorylated sugars. Light stimulates the
      production of dihydroxyacetone phosphate, the initial substrate for sucrose and
      starch synthesis, and inhibits the degradative pathways in the chloroplast.
      Phosphate inactivates reactions of synthesis and activates reactions of
      degradation. Among the phosphorylated sugars a special role is allocated to
      fructose 2,6-bisphosphate, which is present in the cytoplasm at very low
      concentrations and inhibits sucrose synthesis directly by inactivating
      pyrophosphatedependent phosphofructokinase. The synthesis of sucrose plays a
      central role in the partitioning of photosynthetic carbon. The cytoplasmic
      enzymes, fructose bisphosphate phosphatase and sucrose phosphate synthase are
      likely key points of regulation. The regulation is carried out by several
      effector metabolites. Fructose 2,6-bisphosphate is likely to be the main
      coordinator of the rate of sucrose synthesis, hence of photosynthetic carbon
      partitioning between sucrose and starch. 

PMID- 24442926
TI  - Treatment of oral mucositis pain following radiation therapy for head-and-neck
      cancer using a bioadhesive barrier-forming lipid solution.
AB  - PURPOSE: CAM2028, a vehicle that forms a bioadhesive lipid barrier when applied
      to the oral mucosa, was developed as a carrier system for local delivery of
      benzydamine, an NSAID used for pain relief in oral mucositis. This trial compared
      the analgesic effect of CAM2028 plus benzydamine (CAM2028-benzydamine) with
      unmedicated CAM2028 (CAM2028-control) for the treatment of oral mucositis in
      patients with head-and-neck cancer. METHODS: Thirty-eight study participants were
      enrolled during their 3rd to 4th week of radiation therapy. Participants were
      required to have symptomatic oral mucositis (WHO Grade 2 or above) at screening
      and pain scores of at least 6 on an 11-point Likert scale at screening and on
      each day before treatment with study medication. After undergoing radiation,
      patients were administered a single dose of CAM2028-control or CAM2028
      benzydamine 2 days apart, in a randomized crossover fashion. Pain was assessed
      over the following 8 h. RESULTS: With both treatments, patients experienced a
      mean 40 % decrease in pain intensity at 6 h (the primary study endpoint). Both
      treatments resulted in significant pain relief within 5 min of application that
      was evident during the entire 8-h assessment period. There was no difference in
      pain relief between the two interventions at any time point. Both treatments were
      safe and well tolerated. CONCLUSIONS: CAM2028-benzydamine and CAM2028-control
      were both efficacious in reducing pain in patients with oral mucositis related to
      radiation therapy for head-and-neck cancer. Analgesic effects of both medications
      were immediate, clinically significant, and persistent for up to 8 h.

PMID- 24442927
TI  - Comment to the paper: Acceleration of peripheral nerve regeneration using nerve
      conduits in combination with induced pluripotent stem cell technology and a basic
      fibroblast growth factor drug delivery system by M. Ikeda, T. Uemura, K.
      Takamatsu, M. Okada, K. Kazuki, Y. Tabata, Y. Ikada, H. Nakamura, J Biomed Mater
      Res A. 2013 Jun 3 doi: 10.1002/jbm.a.34816.

PMID- 24442929
TI  - Friedrich Trendelenburg: historical background and significant medical
      contributions.
AB  - Friedrich Trendelenburg's name is widely known today because it is associated
      with the Trendelenburg position. However, Trendelenburg made many other valuable
      contributions to the field of medicine, including a test, a gait, and a sign. A
      historical review of his life helps to elucidate the factors that contributed to
      his innovative approaches and techniques. Both Trendelenburg's mentors in his
      early years and the influences upon him throughout his professional career
      contributed to his development as a pioneer of surgery, anesthesia, and clinical
      diagnostics.

PMID- 24442930
TI  - On the structures, lifetimes, and infrared spectra of alkylmercury hydrides.
AB  - A series of six small alkylmercury hydrides of the general formula RHgH with
      R=methyl, ethyl, n-propyl, isopropyl, n-butyl, and 3-butenyl were obtained by
      reduction in vacuo of the corresponding mercury halide with tributyltin hydride
      in the presence of a radical inhibitor. These very reactive compounds, which have
      to be removed from the reaction mixture as they are formed, were characterized by
      (1)H NMR and (13)C NMR spectroscopy. The IR spectra of n-propyl-, isopropyl-, n
      butyl-, and 3-butenylmercury hydride were recorded for the first time. All
      compounds were then studied by density functional theory calculations on the
      basis of a recent theoretical assessment for alkylmercury compounds performed by
      our group. Comparison of the experimental and theoretical results allowed the
      assignment of the vibrational modes in an unambiguous way, in spite of the low
      intrinsic stability of some of the derivatives investigated. The experimental
      procedure implemented for registering the IR spectra of these unstable species in
      the gas phase allowed us to obtain reasonable estimates of their lifetimes.

PMID- 24442928
TI  - Acute hepatitis C: a 24-week course of pegylated interferon alpha-2b versus a 12
      week course of pegylated interferon alpha-2b alone or with ribavirin.
AB  - Therapy of acute hepatitis C (AHC) has not yet been standardized and several
      issues are still unresolved. This open, randomized, multicenter trial aimed to
      assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN)
      alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin
      (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who
      did not spontaneously resolve by week 12 after onset were consecutively enrolled
      and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 MUg/kg/week) for 24
      or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination
      with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was
      undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological
      response; SVR). All patients were followed for 48 weeks after therapy cessation.
      HCV RNA levels were determined by real-time polymerase chain reaction (limit of
      detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of
      treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis,
      overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44
      (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3,
      respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued
      therapy or were lost to follow-up; thus, sustained response rates with per
      protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3
      respectively. With multivariate analysis, virologic response at week 4 of
      treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well
      tolerated. CONCLUSION: Peg-IFN alpha-2b induces a high SVR in chronically
      evolving AHC patients. Response rates were not influenced by combination therapy
      or treatment duration.

PMID- 24442931
TI  - Deliver us from evil? The temptation, realities, and neuroethico-legal issues of
      employing assessment neurotechnologies in public safety initiatives.
AB  - In light of the recent events of terrorism and publicized cases of mass slayings
      and serial killings, there have been calls from the public and policy-makers
      alike for neuroscience and neurotechnology (neuroS/T) to be employed to intervene
      in ways that define and assess, if not prevent, such wanton acts of aggression
      and violence. Ongoing advancements in assessment neuroS/T have enabled heretofore
      unparalleled capabilities to evaluate the structure and function of the brain,
      yet each and all are constrained by certain technical and practical limitations.
      In this paper, we present an overview of the capabilities and constraints of
      current assessment neuroS/T, address neuro-ethical and legal issues fostered by
      the use and potential misuse of these approaches, and discuss how neuroethics may
      inform science and the law to guide right and sound applications of neuroS/T to
      "deliver us from evil" while not being led into temptations of ampliative claims
      and inapt use. 

PMID- 24442933
TI  - An informatics curriculum for psychiatry.
AB  - Information technology is growing at a tremendous rate, becoming a part of all
      aspects of the practice of psychiatry. Medical informatics is the study of the
      use of information in medicine. As information management becomes a greater part
      of the definition of psychiatric practice, it becomes critical that an
      understanding of medical informatics principles as applied to psychiatric
      practice should be incorporated into psychiatric residency training. The authors
      outline the components and objectives of such a curriculum, focusing on basic
      tasks of patient care, communication, education, and practice management. The
      authors conclude with a discussion of issues affecting implementation, including
      assessment of resources and program planning. 

PMID- 24442932
TI  - Participation in regular leisure-time physical activity among individuals with
      type 2 diabetes not meeting Canadian guidelines: the influence of intention,
      perceived behavioral control, and moral norm.
AB  - BACKGROUND: Most people with type 2 diabetes do not engage in regular leisure
      time physical activity. The theory of planned behavior and moral norm construct
      can enhance our understanding of physical activity intention and behavior among
      this population. PURPOSE: This study aims to identify the determinants of both
      intention and behavior to participate in regular leisure-time physical activity
      among individuals with type 2 diabetes who not meet Canada's physical activity
      guidelines. METHOD: By using secondary data analysis of a randomized computer
      tailored print-based intervention, participants (n = 200) from the province of
      Quebec (Canada) completed and returned a baseline questionnaire measuring their
      attitude, perceived behavioral control, and moral norm. One month later, they
      self-reported their level of leisure-time physical activity. RESULTS: A
      hierarchical regression equation showed that attitude (beta = 0.10, P < 0.05),
      perceived behavioral control (beta = 0.37, P < 0.001), and moral norm (beta =
      0.45, P < 0.001) were significant determinants of intention, with the final model
      explaining 63% of the variance. In terms of behavioral prediction, intention
      (beta = 0.34, P < 0.001) and perceived behavioral control (beta = 0.16, P < 0.05)
      added 17% to the variance, after controlling the effects of the experimental
      condition (R (2) = 0.04, P < 0.05) and past participation in leisure-time
      physical activity (R (2) = 0.22, P < 0.001). The final model explained 43% of the
      behavioral variance. Finally, the bootstrapping procedure indicated that the
      influence of moral norm on behavior was mediated by intention and perceived
      behavioral control. CONCLUSION: The determinants investigated offered an
      excellent starting point for designing appropriate counseling messages to promote
      leisure-time physical activity among individuals with type 2 diabetes.

PMID- 24442934
TI  - Medical students' attitudes toward psychiatry in Greece : an eight-year
      comparison.
AB  - This study is a comparative investigation of the attitudes toward psychiatry of
      two medical student groups who did their undergraduate training in psychiatry in
      1985 and 1993. Attitude assessments were carried out by using the Libertarian
      Mental Health Ideology Scale (LMHIS). The students completed the questionnaire
      twice, at the beginning and at the end of their clerkship. The LMHIS was also
      completed by the teaching staff. Both medical student groups showed a significant
      change in their attitudes toward psychiatry after the end of the training. The
      change consisted of a shift to a more medical orientation. However, the 1993
      group manifested a significantly higher medical orientation both before and after
      their undergraduate training in psychiatry compared with the 1985 group.
      Furthermore, the former group's opinions at the end of their education were
      similar to those of their teaching staff, whereas the 1985 students continued to
      have a lower medical orientation compared with the teaching staff. These findings
      indicate that 1) psychiatric education during medical school may significantly
      mold students' attitudes toward psychiatry and 2) if these medical student groups
      represent the larger Greek society, then significant changes may be occurring in
      the Greek society about attitudes toward psychiatry. 

PMID- 24442935
TI  - Mentoring new faculty in a department of psychiatry.
AB  - A formalized mentoring program was developed in response to several problems
      experienced by new faculty in a department of psychiatry. Goals of the program
      were to facilitate socialization/orientation to academic psychiatry, facilitate
      and improve functioning of faculty, and increase retention of new faculty
      members. A 36-item questionnaire and a program evaluation form were developed to
      evaluate the effectiveness of the program. Significant differences were found for
      the overall mean of all pre- vs. postmeasures and the sum of the items related to
      facilitation of socialization/orientation to academic psychiatry. Mentors and
      mentees evaluated the program as worthwhile and would recommend it to other
      faculty members. 

PMID- 24442936
TI  - A National, Randomized Survey of HIV/AIDS Knowledge and Attitudes Among
      Psychiatrists in Training.
AB  - Given the broad spectrum of medical and psychiatric complications associated with
      HIV (human immunodeficiency virus) disease, HIV-related education is an important
      curriculum topic for all physicians. This study examined the HIV-related
      knowledge and attitudes among psychiatrists in training to evaluate their
      training needs. A survey instrument was developed containing 15 knowledge items,
      15 attitude items, demographic items, and questions concerning how HIV/AIDS
      (acquired immunodeficiency syndrome) affected residency choice and self
      perception of training needs. The questionnaire was mailed to 2,252 psychiatrists
      in training randomly selected and stratified by American Psychiatric Association
      district and postgraduate training year. The sample consisted of 825 respondents
      representing 37% of the initial pool. Knowledge was most lacking in areas dealing
      with HIV-related neuropsychiatric complications and issues concerning HIV/AIDS
      and special populations. In general, the respondents expressed positive attitudes
      about HIV-related issues; however, three items correctly endorsed by fewer than
      75% of the sample dealt specifically with the management of neuropsychiatric
      complications, working with dying patients, and the range of normal sexuality.
      Targeted HIV-related education is needed for psychiatrists in training and
      particularly should encompass neuropsychiatric syndromes and issues of special
      populations. 

PMID- 24442937
TI  - International medical students' career choice, attitudes toward psychiatry, and
      emigration to the United States : examples from India and zimbabwe.
AB  - The selection residents who are international medical graduates can be
      facilitated by knowledge of the context of their training and experience in
      psychiatry; the career opportunities in the country from which they come; and
      their attitudes toward psychiatry, medicine, and the United States. This study
      examines some of these variables as well as the emigration plans of 209 Indian
      and 46 Zimbabwe medical students in their next to last year of medical school.
      Both groups tended to hold positive attitudes toward psychiatry and had good
      experiences with the field. Fifty-six percent of the Indian students indicated
      that they had at least thought about emigrating to the United States for
      postgraduate training, and 22% had definite plans. Only 25% of the Zimbabwe
      students had thought about U.S. emigration, and a mere 2% had plans. Indian, as
      well as other IMGs, will continue to be a presence in U.S. residency programs,
      and those who have a preresidency stay in the United States may come to know and
      appreciate psychiatry more as they become more familiar with the field and with
      American culture. 

PMID- 24442938
TI  - Downsizing psychiatric residency programs : a pilot study.
AB  - Under the varied pressures of decreasing recruitment of American medical school
      graduates into psychiatry, the thrust of health care policymakers to decrease the
      production of specialist physicians, and financial cutbacks for training by
      hospitals, universities, and governments at all levels, many psychiatric training
      programs are considering downsizing or have already implemented plans to do so.
      The authors describe the motivations, early experiences, anticipated concerns,
      and thoughts regarding downsizing obtained from interviews or questionnaires
      provided by 17 programs in 1993. On the basis of the authors' experiences, some
      recommendations are offered for the many programs likely to deal with this issue
      in the future. 

PMID- 24442939
TI  - Pharmaceutical companies and academic departments of psychiatry : a call for
      ethics education.
AB  - Pharmaceutical companies contribute over $13,000 per physician for promotion and
      advertisement of products. Psychiatrists and psychiatric residents are influenced
      by these interactions. Two recommendations to psychiatric residency training
      programs are offered: Incorporation of ethics education into teaching forums and
      the establishment of specific ground rules that would govern the interaction of
      pharmaceutical companies with psychiatric residents. 

PMID- 24442941
TI  - Useful websites for psychiatrists.

PMID- 24442943
TI  - A survey of state financing of psychiatry residency programs.
AB  - With upcoming cuts in graduate medical education funding, it is likely that many
      psychiatry residencies will be searching for new sources of revenue. State
      funding of residency programs is one possible avenue. The authors surveyed all
      Accreditation Council for Graduate Medical Education-accredited psychiatry
      residency programs to assess the present dimensions of state funding. Some
      programs in both publicly funded and private settings receive large proportions
      of their budgets from the state. Service commitments are common. State support of
      psychiatry residency education is currently an important source of funding and
      could become even more important in the near future. 

PMID- 24442944
TI  - Characteristics of directors of medical student education in psychiatry.
AB  - A 27-item questionnaire that focused on general characteristics of directors of
      medical student education in psychiatry was sent to 132 U.S. medical schools
      (return rate: 64%, or 84 questionnaires). A tally of the responses revealed that
      the directors are relatively young, mostly male, with some appointed to their
      position relatively soon after resi-dency. They have been in this position for a
      relatively short time, and their replacement rate is fairly high. They are
      frequently on a clinical track, generating their income from several sources. The
      women did not endorse research as a major activity as often as the men. The
      implications of these findings and some recommendations are discussed. 

PMID- 24442945
TI  - Moonlighting by psychiatric residents.
AB  - Much of the literature on resident moonlighting has been editorial in nature.
      Very little information on psychiatric residents' moonlighting practices and
      attitudes exists. The authors developed an instrument that was mailed to survey
      the chief residents of all 203 Accreditation Council for Graduate Medical
      Education-approved psychiatry residencies, with 137 (67.5%) programs responding.
      According to the responses, the percentage of residents moonlighting increased
      with each successive year of training, with an average of 31 hours per resident
      per month. The two major reasons given for moonlighting were payment of living
      expenses (58%) and repayment of student loans (24%). No supervision was provided
      to 22% of the moonlighting residents. Only 10% of the programs proscribed
      moonlighting by their residents. To better assess the positive and negative
      effects of moonlighting, it is time to truly monitor and guide the moonlighting
      experience for both residents and their programs. 

PMID- 24442946
TI  - Patient suicide in psychiatry residency programs : a national survey of training
      and postvention practices.
AB  - Patient suicide, which has been shown to have great emotional impact upon
      trainees, is experienced by as many as one in three psychiatry residents. The
      authors report the results of a national survey of psychiatry residency training
      programs (N=166) that asked about 1) current training practices in the area of
      suicide and 2) required or recommended procedures in the event of suicide by a
      resident's patient. Results show that programs commonly offer training in the
      assessment and treatment of suicidal patients, but the question remains as to
      whether the training is adequate to meet the challenges of working with suicidal
      individuals. Results also reflect considerable variability in "postvention"
      practices among programs and training settings, especially in terms of what steps
      should be taken when a trainee's patient commits suicide. Implications of the
      survey for residency training programs are discussed. 

PMID- 24442947
TI  - Gender-related group dynamics in problem-based learning : a retrospective study.
AB  - As problem-based learning (PBL) techniques play an increasingly important role in
      medical school curricula, programs will require an understanding of which
      variables enhance or inhibit learning. Through a retrospective study of an
      "experiment" in which male and female medical students were separated into single
      gender tutorial groups, the authors describe gender differences in the styles of
      participation and subjective experi-ence of men and women in mixed-gender and
      single-gender tutorial groups. The women students noted an increase in their
      comfort level in the all-women tutorial group and felt that learning about their
      own styles in this group helped them participate more effec-tively in coed groups
      and later on in other professional settings. The authors make rec-ommendations
      concerning the implementation of PBL in medical school curricula. 

PMID- 24442950
TI  - Errors in differential infrared carbon dioxide analysis resulting from water
      vapor.
AB  - Water vapor was added differentially to the gas streams entering the cells of
      three makes of differential infrared carbon dioxide analysers. Analyser
      deflections were compared with those expected from dilution of the carbon dioxide
      by the additional gas. Tests were made at 0, 365, and 730 cm(3) m(-3)
      concentrations of carbon dioxide, and with the dewpoint in one cell of the
      analysers held constant at 15, 20, or 25 degrees C. None of the analysers always
      responded in the ways predicted from dilution. The results showed that errors of
      a few cm(3) m(-3) could occur in estimates of carbon dioxide differentials using
      the theoretical correction for dilution. Furthermore the amount of error varied
      with the carbon dioxide range, the difference in water content, and in some cases
      the dewpoint range. 

PMID- 24442949
TI  - Incorporating significant amino acid pairs and protein domains to predict RNA
      splicing-related proteins with functional roles.
AB  - Machinery of pre-mRNA splicing is carried out through the interaction of RNA
      sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g.
      spliceosome and splicing factors). Alternative splicing, which is an important
      post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA
      isoforms, which encodes proteins with functional diversities. However, the
      regulation of RNA splicing is not yet fully elucidated, partly because SRPs have
      not yet been exhaustively identified and the experimental identification is labor
      intensive. Therefore, we are motivated to design a new method for identifying
      SRPs with their functional roles in the regulation of RNA splicing. The
      experimentally verified SRPs were manually curated from research articles.
      According to the functional annotation of Splicing Related Gene Database, the
      collected SRPs were further categorized into four functional groups including
      small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and
      Novel Spliceosome Protein. The composition of amino acid pairs indicates that
      there are remarkable differences among four functional groups of SRPs. Then,
      support vector machines (SVMs) were utilized to learn the predictive models for
      identifying SRPs as well as their functional roles. The cross-validation
      evaluation presents that the SVM models trained with significant amino acid pairs
      and functional domains could provide a better predictive performance. In
      addition, the independent testing demonstrates that the proposed method could
      accurately identify SRPs in mammals/plants as well as effectively distinguish
      between SRPs and RNA-binding proteins. This investigation provides a practical
      means to identifying potential SRPs and a perspective for exploring the
      regulation of RNA splicing. 

PMID- 24442951
TI  - Primary photochemistry in photosystem-I.
AB  - In this review, the main research developments that have led to the current
      simplified picture of photosystem I are presented. This is followed by a
      discussion of some conflicting reports and unresolved questions in the
      literature. The following points are made: (1) the evidence is contradictory on
      whether P700, the primary donor, is a monomer or dimer of chlorophyll although at
      this time the balacnce of the evidence points towards a monomeric structure for
      P700 when in the triplet state; (2) there is little evidence that the iron sulfur
      centers FA and FB act in series as tertiary acceptors and it is as likely that
      they act in parallel under physiological conditions; (3) a role for FX, probably
      another iron sulfur centrer, as an obligatory electron carrier in forward
      electron transfer has not been proven. Some evidence indicates that its reduction
      could represent a pathway different to that involving FA and FB; (4) the decay of
      the acceptor 'A2 (-)' as defined by optical spectroscopy corresponds with 700(+)
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      some circumstances but under other conditions it probably corresponds with
      P700(+) A1 (-) recombination; (5) P700(+) A1 (-) recombination as originally
      observed by optical spectroscopy is probably due to the decay of the P700 triplet
      state; (6) the acceptor A1 (-) as defined by EPR may be a special semiquinone
      molecule; (7) A0 is probably a chlorophyll a molecule which acts as the primary
      acceptor. Recombination of P700(+) A0 (-) gives rise to the P700 triplet state.A
      working model for electron transfer in photosystem I is presented, its general
      features are discussed and comparisons with other photosystems are made. 

PMID- 24442952
TI  - Electron transport in green photosynthetic bacteria.
AB  - Green bacteria make up two of the four families of anoxygenic photosynthetic
      prokaryotes. The two families have similar pigment compositions and membrane fine
      structure, and both contain a specialized antenna structure known as a
      chlorosome. The primary photochemistry and electron transport pathways of the two
      groups are, however, quite distinct. The anaerobic green bacteria (Chlorobiaceae)
      contain low-potential iron-sulfur proteins as early electron acceptors and can
      directly reduce NAD(+) in a manner reminiscent of Photosystem I of oxygenic
      organisms. The facultatively aerobic green bacteria (Chloroflexaceae) contain
      quinone-type acceptors and have an overall pattern of electron transport very
      similar to that found in purple bacteria. Many aspects of energy storage in green
      bacteria, especially photophosphorylation and the role of cytochrome b/c
      complexes in electron transport, remain poorly understood. 

PMID- 24442953
TI  - Mechanisms of quinol oxidation in photosynthesis.
AB  - The mechanisms by which para-benzoquinols can be oxidized is reviewed. Emphasis
      is placed on the information available from chemical and electrochemical studies
      which may provide insight into the biochemical mechanisms of plastoquinol
      oxidation in the chloroplast. Three mechanisms of quinol oxidation are possible:
      (1) The removal of an electron from the quinol, QH inf2 (sup.t) , directly to
      produce the radical cation, QH 2 (.+) . This may be achieved electrochemically
      only at very high potential in acidic media. The reaction may be of relevance to
      D1, the donor to P-680. (2) The removal of an electron from the anionic quinol.
      QH(-), formed by quinol deprotonation. It is likely that the catalytic mechanism
      of the cytochrome bf complex involves this mechanism. (3) The removal of an
      electron from the dianionic quinol, Q(2-). This route will be dominant only under
      basic or aprotic conditions and at very low potentials. 

PMID- 24442954
TI  - Calcium depletion alters energy transfer and prevents state changes in intact
      Anacystis.
AB  - A time-dependent loss of Photosystem II (PS II) activity seen in Anacystis
      nidulans grown without Ca(2+) was paralleled by a loss in chlorophyll (Chl) a
      fluorescence of variable yield which reflects inhibition of 'Q' reduction and of
      state changes. Both inhibitions were fully reversed by the addition of Ca(2+) to
      the growth medium. The lack of state changes in Ca(2+)-depleted cells was
      confirmed in 77 K fluorescence difference spectra of light versus dark-adapted
      cells.Absorption spectra of control and of Ca(2+)-depleted cells were identical
      whether measured at room temperature or at 77 K. Fluorescence emission spectra
      measured at 39 degrees C (cell growth temperature) demonstrated higher yields in
      Ca(2+)-depleted cells compared to controls. Fluorescence emission spectra at 77 K
      also produced higher yields in Ca(2+)-depleted cells but the increased
      fluorescence at this temperature occurred principally at 683 nm. The increased
      relative fluorescence yield in Ca(2+)-depleted samples results from light
      absorbed by phycocyanin (PC), but not from light absorbed almost exclusively by
      Chl. The 683 run fluorescence peak probably represents increased allophycocyanin
      (APC) emission as intact phycobilisomes become energetically disassociated from
      the photosynthetic apparatus. This inferred disassociation occurred only after
      PSII activity was mostly inhibited in Ca(2+)-depleted cells, and was not fully
      reversible. 

PMID- 24442955
TI  - CO2 exchange characteristics during dark-light transitions in wild-type and
      mutant Chlamydomonas reinhardii cells.
AB  - A burst of net CO2 uptake was observed during the first 3-4 min after the onset
      of illumination in both wild-type Chlamydomonas reinhardii in which carbonic
      anhydrase was chemically inhibited with ethoxyzolamide and in a mutant of C.
      reinhardii (ca-1-12-1C) deficient in carbonic anhydrase activity. The burst was
      followed by a rapid decrease in the CO2 uptake rate so that net evolution often
      occurred. After a 2-3 min period of CO2 evolution, net CO2 uptake again increased
      and ultimately reached a steady-state, positive rate. From [(14)CO2]-tracer
      studies it was determined that CO2 fixation proceeded at a nearly linear rate
      throughout the period of illumination. Thus, prior to reaching a steady state,
      there was a rapid accumulation of inorganic carbon inside the cells which
      apparently reached a supercritical concentration and the excess was excreted,
      causing a subsequent efflux of CO2. A post illumination burst of net CO2 efflux
      was also observed in ethoxyzolamide-inhibited wild type and ca-1 mutant cells,
      but not in the unihibited wild type. [(14)CO2]-tracer experiments revealed that
      this burst was the result of a collapse of a large internal inorganic carbon pool
      at the onset of darkness rather than a photorespiratory post-illumination burst.
      These results indicate that upon illumination, chemical or genetic inhibition of
      carbonic anhydrase initially causes an accumulation of excess inroganic carbon in
      C. reinhardii cells, and that unknown regulatory mechanisms correct for this
      imbalance by first excreting the excess inorganic carbon and then, after several
      dampened oscillations, achieving an equilibrium between bicarbonate uptake,
      bicarbonate dehydration, and CO2 fixation. 

PMID- 24442957
TI  - Editorial note.

PMID- 24442956
TI  - Site of salicylaldoxime interaction with photosystem II.
AB  - The reversible inhibition of Photosystem II by salicylaldoxime was studied in
      spinach D-10 particles by fluorescence, optical absorption, and electron spin
      resonance spectroscopy. In the presence of 15 mM salicylaldoxime, the initial
      fluorescence yield was raised to the level of the maximum fluorescence,
      indicating efficient charge recombination between reduced pheophytin (Ph) and
      P680(+). In agreement with the rapid (ns) backreaction expected between Ph(-) and
      P680(+), the optical absorption transient at 820 mm was not observed. When the
      particles were washed free of salicylaldoxime, the optical absorption transient
      resulting from the rereduction of P680(+) was restored to the us timescale. These
      results, along with the previously observed inhibition of electron transport
      reactions and diminution of the 515-nm absorption change in chloroplasts
      [Golbeck, J.H. (1980) Arch Biochem Biophys 202, 458-466], are consistent with a
      site of inhibition between Ph and QA in Photosystem II. ESR Signal IIf and Signal
      Its were abolished in the presence of 25 mM salicylaldoxime, but both signals
      could be recovered by washing the D-10 particles free of the inhibitor. The loss
      of Signal Ilf is most likely a consequence of the inhibition between Ph and QA;
      the rapid charge recombination between Ph(-) and P680(+) would preclude electron
      transfer from an electron donor on the oxidizing side of Photosystem II. The loss
      of Signal Its may be due to a change in the environment of the donor complex such
      that the semiquinone radical giving rise to Signal Its interacts with a nearby
      reductant. 

PMID- 24442958
TI  - Reduction of the pro-inflammatory response by tetrandrine-loading poly(L-lactic
      acid) films in vitro and in vivo.
AB  - Inflammatory response of implantable biomaterials and drug delivery vehicles,
      driven by the reaction of macrophages to foreign body particles released from the
      implant, is an urgent problem to resolve. Despite this, little is known about the
      inflammatory molecular mechanism following the implantation of biomaterials and
      the evaluation of anti-inflammatory biomaterials. In this study, tetrandrine
      (TET) was loaded into poly (l-lactic acid) (PLLA) films to assess the anti
      inflammatory effects in vitro and in vivo. The water contact angle measurement
      indicated the variation of hydrophilicity and the electron spectroscopy for
      chemical analysis (ESCA) data suggested that TET was loaded into PLLA films,
      which were marked as enriched with nitrogen atoms. TET-loading PLLA films had
      satisfactory sustained releasing behavior in salicylic acid solution with
      accelerating release. RAW 264.7 macrophages cultured in TET-loading PLLA films
      maintained lower levels of chemokines, cytokines, and enzymes involved in the
      inflammatory process, such as NO, TNF-alpha, IL-6, iNOS, COX-2 than control PLLA
      films, suggesting that TET-loading PLLA films could regulate the mRNA expression
      and protein expression to reduce the inflammatory response in macrophages. The
      degree of inflammatory reaction for the implant with the TET-loading PLLA films
      was significantly less severe than that close to control PLLA films in 4, 12
      weeks after operation in rats. The present study will provide a new method to
      evaluate and treat the biocompatibility related to inflammatory response for
      implanted biomaterials and drug delivery system.

PMID- 24442959
TI  - Associations between Mycobacterium ulcerans and aquatic plant communities of West
      Africa: implications for Buruli ulcer disease.
AB  - Numerous studies have associated Buruli ulcer (BU) disease with disturbed aquatic
      habitats; however, the natural reservoir, distribution, and transmission of the
      pathogen, Mycobacterium ulcerans, remain unknown. To better understand the role
      of aquatic plants in the ecology of this disease, a large-scale survey was
      conducted in waterbodies of variable flow throughout three regions of Ghana,
      Africa. Our objectives were to characterize plant communities and identify
      potential relationships with M. ulcerans and other mycolactone-producing
      mycobacteria (MPM). Waterbodies with M. ulcerans had significantly different
      aquatic plant communities, with submerged terrestrial plants identified as
      indicators of M. ulcerans presence. Mycobacterium ulcerans and MPM were detected
      on 14 plant taxa in emergent zones from both lotic and lentic waterbodies in
      endemic regions; however, M. ulcerans was not detected in the non-endemic Volta
      region. These findings support the hypothesis that plants provide substrate for
      M. ulcerans colonization and could act as potential indicators for disease risk.
      These findings also suggest that M. ulcerans is a widespread environmental
      bacteria species, but that it is absent or reduced in regions of low disease
      incidence. A better understanding is needed regarding the mechanistic
      associations among aquatic plants and M. ulcerans for identifying the mode of
      transmission of BU disease. 

PMID- 24442960
TI  - Atmospheric polycyclic aromatic hydrocarbons and isomer ratios as tracers of
      biomass burning emissions in Northern India.
AB  - Emission from large-scale post-harvest agricultural-waste burning (paddy-residue
      burning during October-November and wheat-residue burning in April-May) is a
      conspicuous feature in northern India. The poor and open burning of agricultural
      residue result in massive emission of carbonaceous aerosols and organic
      pollutants to the atmosphere. In this context, concentrations of atmospheric
      polycyclic aromatic hydrocarbons (PAHs) and their isomer ratios have been studied
      for a 2-year period from a source region (Patiala: 30.2 degrees N; 76.3 degrees
      E) of two distinct biomass burning emissions. The concentrations of 4-6 ring PAHs
      are considerably higher compared to 2-3 ring PAHs in the ambient particulate
      matter (PM2.5). The crossplots of PAH isomer ratios, fluoranthene / (fluoranthene
      + pyrene) and indeno[1,2,3-cd]pyrene/(indeno[1,2,3-cd]pyrene +
      benzo[g,h,i]perylene) for two biomass burning emissions, exhibit distinctly
      different source characteristics compared to those for fossil-fuel combustion
      sources in south and south-east Asia. The PAH isomer ratios studied from
      different geographical locations in northern India also exhibit similar
      characteristics on the crossplot, suggesting their usefulness as diagnostic
      tracers of biomass burning emissions. 

PMID- 24442961
TI  - Characterization and concentrations of polycyclic aromatic hydrocarbons in
      emissions from different heating systems in Damascus, Syria.
AB  - Traffic has long been recognized as the major contributor to polycyclic aromatic
      hydrocarbon (PAH) emissions to the urban atmosphere. Stationary combustion
      sources, including residential space heating systems, are also a major
      contributor to PAH emissions. The aim of this study was to determine the profile
      and concentration of PAHs in stack flue gas emissions from different kinds of
      space heaters in order to increase the understanding of the scale of the PAH
      pollution problem caused by this source. This study set out to first assess the
      characteristics of PAHs and their corresponding benzo[a]pyrene equivalent
      emissions from a few types of domestic heaters and central heating systems to the
      urban atmosphere. The study, enabled for the first time, the characterization of
      PAHs in stationary combustion sources in the city of Damascus, Syria. Nine
      different types of heating systems were selected with respect to age, design, and
      type of fuel burned. The concentrations of 15 individual PAH compounds in the
      stack flue gas were determined in the extracts of the collected samples using
      high-performance liquid chromatography system (HPLC) equipped with ultraviolet
      visible and fluorescence detectors. In general, older domestic wood stoves caused
      considerably higher PAH emissions than modern domestic heaters burning diesel
      oil. The average concentration of SigmaPAH (sum of 15 compounds) in emissions
      from all types of studied heating systems ranged between 43 +/- 0.4 and 316 +/-
      1.4 MUg/m(3). Values of total benzo[a]pyrene equivalent ranged between 0.61 and
      15.41 MUg/m(3). 

PMID- 24442962
TI  - Influence of soil and hydrocarbon properties on the solvent extraction of high
      concentration weathered petroleum from contaminated soils.
AB  - Petroleum ether was used to extract petroleum hydrocarbons from soils collected
      from six oil fields with different history of exploratory and contamination. It
      was capable of fast removing 76-94 % of the total petroleum hydrocarbons
      including 25 alkanes (C11-C35) and 16 US EPA priority polycyclic aromatic
      hydrocarbons from soils at room temperature. The partial least squares analysis
      indicated that the solvent extraction efficiencies were positively correlated
      with soil organic matter, cation exchange capacity, moisture, pH, and sand
      content of soils, while negative effects were observed in the properties
      reflecting the molecular size (e.g., molecular weight and number of carbon atoms)
      and hydrophobicity (e.g., water solubility, octanol-water partition coefficient,
      soil organic carbon partition coefficient) of hydrocarbons. The high
      concentration of weathered crude oil at the order of 10(5) mg kg(-1) in this
      study was demonstrated adverse for solvent extraction by providing an obvious
      nonaqueous phase liquid phase for hydrocarbon sinking and increasing the
      sequestration of soluble hydrocarbons in the insoluble oil fractions during
      weathering. A full picture of the mass distribution and transport mechanism of
      petroleum contaminants in soils will ultimately require a variety of studies to
      gain insights into the dynamic interactions between environmental indicator
      hydrocarbons and their host oil matrix. 

PMID- 24442963
TI  - Preparation of regenerated keratin sponge from waste feathers by a simple method
      and its potential use for oil adsorption.
AB  - In this work, pigeon feathers, a kind of totally waste by-product from the
      poultry industry, were utilized to fabricate a highly porous keratin sponge in a
      very simple way by freeze-drying treatment of the dissolved keratin solution, and
      applied for the first time as an oil adsorbent. An improved method was proposed
      to dissolve the feather keratin using the inexpensive sodium disulfite as the
      reducing reagent for sulfitolysis reaction, with a much lower concentration of
      all involving reaction regents. Moreover, the regenerated keratin sponges
      obtained a high oil adsorption capacity of above 30 g/g for both liquid paraffin
      and soybean oil, as well as a good oil holding ability, suggesting that this
      keratin sponge might be a potential for use as oil adsorbent. 

PMID- 24442964
TI  - Impacts of population growth and economic development on water quality of a lake:
      case study of Lake Victoria Kenya water.
AB  - Anthropogenic-induced water quality pollution is a major environmental problem in
      freshwater ecosystems today. As a result of this, eutrophication of lakes occurs.
      Population and economic development are key drivers of water resource pollution.
      To evaluate how growth in the riparian population and in the gross domestic
      product (GDP) with unplanned development affects the water quality of the lake,
      this paper evaluates Lake Victoria Kenyan waters basin. Waters quality data
      between 1990 and 2012 were analyzed along with reviews of published literature,
      papers, and reports. The nitrate-nitrogen (NO3-N), soluble phosphorus (PO4-P),
      chlorophyll a, and Secchi transparencies were evaluated as they are key water
      quality indicators. The NO3-N increased from 10 MUg l(-1) in 1990 to 98 MUg 1(-1)
      in 2008, while PO4-P increased from 4 MUg l(-1) in 1990 to 57 MUg l(-1) in 2008.
      The population and economic growth of Kenya are increasing with both having
      minimums in 1990 of 24.143 million people and 12.18 billion US dollars, to
      maximums in 2010 of 39.742 million people and 32.163 billion US dollars,
      respectively. A Secchi transparency is reducing with time, indicating an
      increasing pollution. This was confirmed by an increase in aquatic vegetation
      using an analysis of moderate resolution imaging spectroradiometer (MODIS) images
      of 2000 and 2012 of Kenyan waters. This study found that increasing population
      and GDP increases pollution discharge thus polluting lakes. One of major factors
      causing lake water pollution is the unplanned or poor waste management policy and
      service. 

PMID- 24442965
TI  - Marine sponges with contrasting life histories can be complementary biomonitors
      of heavy metal pollution in coastal ecosystems.
AB  - In this study, we compared the usefulness of a long-living sponge (Hymeniacidon
      heliophila, Class Demospongiae) and a short-living one (Paraleucilla magna, Class
      Calcarea) as biomonitors of metallic pollution. The concentrations of 16 heavy
      metals were analyzed in both species along a gradient of decreasing pollution
      from the heavily polluted Guanabara Bay to the less impacted coastal islands in
      Rio de Janeiro, SE Brazil (SW Atlantic). The levels of most elements analyzed
      were higher in H. heliophila (Al, Co, Cr, Cu, Fe, Mn, Ni, Hg, Ni, and Sn) and P.
      magna (Ni, Cu, Mn, Al, Ti, Fe, Pb, Co, Cr, Zn, and V) collected from the heavily
      polluted bay when compared with the cleanest sites. Hymeniacidon heliophila
      accumulates 11 elements more efficiently than P. magna. This difference may be
      related to their skeleton composition, histological organization, symbiont
      bacteria and especially to their life cycle. Both species can be used as a
      biomonitors of metallic pollution, but while Hymeniacidon heliophila was more
      effective in concentrating most metals, Paraleucilla magna is more indicated to
      detect recent pollutant discharges due to its shorter life cycle. We suggest that
      the complementary use of species with contrasting life histories can be an
      effective monitoring strategy of heavy metals in coastal environments. 

PMID- 24442966
TI  - Taxonomy for methods of resource use measurement.
AB  - Resource use measures, including forms, diaries and questionnaires, are
      ubiquitous in trial-based economic evaluations in the UK. However, there are
      concerns about the accuracy of how they are described, which limits the
      transparency of reporting. We developed a simple and structured taxonomy for
      methods of resource use measurement by examining 94 resource use measures (RUMs)
      employed within clinical trials, conducting a descriptive synthesis of the
      extracted data and soliciting wider opinion during a period of consultation. The
      reporting of RUMs was found to be varied and inconsistent. Our new taxonomy,
      which considered the views of 20 consultees, requires that RUMs are reported with
      a description of the following: (i) the source of data (patient; patient proxy,
      e.g. carer, parent or guardian; observation of contemporary events; medical
      records; or other databases); (ii) who completes the RUM (patient or their proxy,
      and researcher or health care professional); (iii) how it is administered (to
      self [the patient], face to face or telephone); (iv) how it is recorded (form,
      questionnaire, log or diary); and (v) medium of recording (e.g. paper or
      electronically). Based on the present analysis, we have developed a taxonomy for
      RUMs that should result in data collection methods being described more
      accurately.

PMID- 24442967
TI  - Analysis of the petrous portion of the internal carotid artery: landmarks for an
      endoscopic endonasal approach.
AB  - OBJECTIVES/HYPOTHESIS: While there are many benefits to the endoscopic endonasal
      approach to the infratemporal fossa, involvement of the petrous portion of the
      internal carotid artery (ICA) poses a unique challenge. The endoscopic endonasal
      approach requires establishing the relationship of the petrous ICA to anatomical
      landmarks to guide the surgeon. This study evaluates the relationship of petrous
      ICA to specific anatomic landmarks, both radiographically and through cadaveric
      dissections. STUDY DESIGN: Cadaveric and radiographic study. METHODS: An
      endoscopic endonasal approach was used to access the petrous carotid and
      infratemporal fossa. Dissections exposed the petrous portion of the carotid
      artery and identified the foramen rotundum, ovale, and spinosum. Both anatomical
      and radiographic representations of these landmarks were then evaluated and
      compared relative to the petrous carotid. RESULTS: The endoscopic endonasal
      approach to the infratemporal fossa with exposure of the petrous ICA afforded
      complete visualization of the entire segment of this portion of the ICA with
      limited anatomical obstruction. The foramen rotundum, ovale, and spinosum were
      successfully identified and dissected with preservation of their neuro/vascular
      contents. Computed tomography analysis calculated a mean distance to the petrous
      ICA of 16.34 mm from the foramen rotundum, 4.88 mm from the ovale, and 5.11 mm
      from the spinosum in males. For females, the values were 16.40 mm from the
      rotundum and 4.36 mm each from the ovale and spinosum. CONCLUSION: An endonasal
      endoscopic approach to the infratemporal fossa with exposure of the petrous ICA
      is feasible. The anatomical landmarks can serve as both radiographic and surgical
      landmarks in this approach.

PMID- 24442968
TI  - Mucosal C-terminal maltase-glucoamylase hydrolyzes large size starch digestion
      products that may contribute to rapid postprandial glucose generation.
AB  - SCOPE: The four mucosal alpha-glucosidases, which differ in their digestive
      roles, generate glucose from glycemic carbohydrates and accordingly can be viewed
      as a control point for rate of glucose delivery to the body. In this study,
      individual recombinant enzymes were used to understand how alpha-glucan oligomers
      are digested by each enzyme, and how intermediate alpha-amylolyzed starches are
      hydrolyzed, to elucidate a strategy for moderating the glycemic spike of rapidly
      digestible starchy foods. METHODS AND RESULTS: The C-terminal maltase
      glucoamylase (ctMGAM, commonly termed "glucoamylase") was able to rapidly
      hydrolyze longer maltooligosaccharides, such as maltotetraose and maltopentaose,
      to glucose. Moreover, it was found to convert larger size maltodextrins, as would
      be produced early in alpha-amylase digestion of starch, efficiently to glucose.
      It is postulated that ctMGAM has the additional capacity to hydrolyze large alpha
      amylase products that are produced immediately on starch digestion in the
      duodenum and contribute to the rapid generation of glucose from starch-based
      meals. CONCLUSION: The findings suggest that partial inhibition of ctMGAM, such
      as by natural inhibitors found in foods, might be used to moderate the early
      stage of high glycemic response, as well as to extend digestion distally; thereby
      having relevance in regulating glucose delivery to the body.

PMID- 24442970
TI  - Beginning and continuing.

PMID- 24442971
TI  - Educating psychiatrists for the 1990s.

PMID- 24442969
TI  - Blockade of the renin-angiotensin system inhibits growth of colorectal cancer
      liver metastases in the regenerating liver.
AB  - Partial hepatectomy (PH), the preferred option for selected patients with
      colorectal cancer liver metastases (CRCLM), is associated with 40-80% tumor
      recurrence rates. Renin-angiotensin system (RAS) blockade inhibits tumor growth
      and has been suggested to improve liver regeneration. We documented the effect of
      RAS blockade on tumor growth and liver regeneration in a murine model. CRCLM
      induction followed by 70% PH was performed on 78 CBA mice. Liver regeneration
      (days 2, 6) and CRCLM tumor load were measured by liver (and tumor) weights,
      percentage of CRCLM burden and tumor nodule count (days 16, 21). mRNA expression
      of the RAS components was characterised. Statistical analysis was performed using
      2-independent sample T test or Mann-Whitney test (SPSS). Captopril did not impair
      liver regeneration. By day 21, Captopril decreased tumor burden (percentage of
      CRCLM in the liver) (48.7 +/- 4.7% control, 24.4 +/- 6.2 Captopril; p = 0.008),
      tumor volume (1046.2 +/- 200.2 mm(3), 388.3 +/- 150.4; p = 0.02), tumor nodule
      count per image field (181.1 +/- 28.5, 68 +/- 17.6; p = 0.005) and tumor
      angiogenesis (71.8 +/- 6.4 vessels/mm(2), 43.1 +/- 7.6; p = 0.015) compared to
      controls. Captopril enhanced tumor apoptosis (1 +/- 0.2%, 2.5 +/- 0.7; p =
      0.028). Liver regeneration and tumor development increased liver ACE levels.
      Blockade of the RAS effectively retarded CRCLM tumor growth at the late stage of
      tumor development within the regenerating liver without impeding liver
      regeneration following PH, via anti-angiogenesis and pro-tumor apoptosis.
      Captopril may be of therapeutic benefit in patients undergoing PH for CRCLM.

PMID- 24442972
TI  - The teacher: an endangered species?

PMID- 24442973
TI  - Applicants' perceptions of psychiatric residency training programs.
AB  - The authors report the results of a survey of senior medical students who matched
      to a PGY-1 position in psychiatry. With a 64% response rate, the authors found
      the following: 1) senior medical students were generally satisfied with the
      program that they plan to attend; 2) the students utilized nonprogrammatic
      features heavily in their decision making; and 3) there appeared to be subgroups
      of students defined by demographic (i.e., gender and age) and decision-making
      properties (i.e., time of decision) that choose programs with fundamentally
      different aims in mind. 

PMID- 24442974
TI  - Teaching guided imagery.
AB  - Guided imagery is a technique useful for teaching and practicing psychodynamic
      assessment and psychotherapy. It combines a state of meditative relaxation with
      the presentation of evocative scenarios that stimulate the imagination to
      spontaneously generate almost dream-like fanciful productions. These "daydreams"
      ordinarily contain highly revealing suppressed and repressed conflicts, wishes,
      affects, perspectives and other aspects of the self. The instructional program
      offered to trainees at the UCLA Neuropsychiatrie Institute for almost two decades
      is described. Suggestions are offered as to how programs that lack faculty
      acquainted with these techniques can further familiarize themselves in order to
      evaluate the techniques' value for their curriculum. 

PMID- 24442975
TI  - Attitudes of foreign medical graduates and u.s. Medical graduates toward mental
      illness.
AB  - One-hundred forty-nine applicants to two residency programs in psychiatry were
      surveyed with the Opinion About Mental Illness (OMI) scale. Stepwise regression
      analyses showed that the place where the applicant was raised was the best
      predictor. In comparison to those raised abroad, those raised in the United
      States tend to be less authoritarian-restrictive inclined, tend to report less
      adherence toward an unsophisticated benevolent approach, and less adherence
      toward an interpersonal-etiology approach. All subjects, whether raised in the
      United States or not, showed similar adherence to the concepts of the mental
      hygiene movement. 

PMID- 24442976
TI  - Implementing a substance abuse curriculum in a medical school.
AB  - Recent attention to the need for integration of substance abuse education
      throughout medical education prompted this description of one such program. 

PMID- 24442977
TI  - A psychotherapy service: preserving a place for psychodynamic teaching.
AB  - Striving for an educational balance between psychodynamics and psychotherapy led
      to the creation of a Psychotherapy Service. Psychodynamic teaching was preserved
      while biological teaching was increased. The history, philosophy, and structure
      of this service, combined with a chart review, give a picture of the kind of
      clinical experience and training available on such a service. 

PMID- 24442978
TI  - Longitudinal exposure to the seriously mentally ill: a halfway house affiliation.
AB  - Psychiatric training takes place predominantly in institutional settings such as
      hospitals and outpatient clinics. There are significant benefits associated with
      training in community "field" sites. Conversely, training programs can be
      valuable resources for agencies providing residential and/or rehabilitative care
      for the mentally ill The authors discuss advantages to such affiliations and
      illustrate these with the affiliation of a halfway house with a psychiatry
      residency training program. 

PMID- 24442979
TI  - The transference-countertransference phenomenon: a requirement for training.
AB  - Dr. Morton F. Reiser's article, "Are psychiatric deucators 'Losing the Mind'?"
      included a description of experiences with residents who do not appear to
      understand the phenomenon of psychotherapy and, in particular, the issues of
      transference and counter-transference (1). His residents also seemed to be more
      interested in tinkering with drugs and providing support than in understanding,
      with curiosity, the motivation of patients and what goes on in the human mind.
      Transference here is meant to be strong feelings that a patient develops towards
      a therapist that are determined by the patient's past experiences.
      Countertransference is an unconscious reaction to the patient's transference.
      Counter-transference becomes conscious as it is worked upon in supervision and
      distinguished from other feelings the therapist has about the patient. 

PMID- 24442980
TI  - Recruitment conference on child and adolescent psychiatry.

PMID- 24442981
TI  - The concept of governance in dual-use research.
AB  - The rapid advance of life science within the context of increased international
      concern over the potential misuse of findings has resulted in the lack of
      agreement on the issues of responsibility, control and collaboration. This
      progress of knowledge outpaces the efforts of creating moral and legal guidelines
      for the detection and minimization of the risks in the research process. There is
      a need to identify and address normative aspects of dual-use research. This paper
      focuses on the issues of safety and global collaboration in life science research
      by highlighting the importance of openness, enabling policies and cooperative
      governance. These safeguards are believed to reduce the risks related to the
      misuse of science while enabling the important research to move forward. The
      paper addresses the need for a better definition of dual use concept and, based
      on the historical precedents, explores the moral concerns and governmental
      strategies of dual-use research. The three necessary moves in addressing the
      issue of security in life sciences are suggested: the move from constraining to
      enabling types of policies, the move from secrecy to openness, and the move from
      segregation to integration of the public voice. 

PMID- 24442982
TI  - Up-regulation of neuronal and astrocytic GLT-1 mRNA in the hippocampal CA1
      subfield during the induction of brain ischemic tolerance in rats.
AB  - Our previous study showed that 3-min cerebral ischemic preconditioning (CIP) up
      regulated the expression of glial glutamate transporter-1 (GLT-1) protein, which
      protects pyramidal neurons, allowing them to survive an 8-min ischemic insult
      that usually induces severe delayed neuronal death in the hippocampal CA1
      subfield. In the present study, in situ hybridization and immunohistochemistry
      were used to observe whether GLT-1 mRNA is modulated and whether actrocytes
      and/or neurons express GLT-1 mRNA during the induction of brain ischemic
      tolerance. We observed that GLT-1 mRNA is expressed in neurons and astrocytes in
      the hippocampal CA1 subfield. The expression of GLT-1 mRNA was significantly down
      regulated in both neurons and astrocytes after the 8-min lethal ischemic insult.
      CIP for 3 min increased the expression of GLT-1 mRNA in neurons and astrocytes,
      and induced the elongation of the astrocytic processes around pyramidal neurons.
      It may be concluded that CIP performed 2 days before lethal ischemic insult
      activated astrocytes, which resulted in an increased number of lengthened
      processes expressing high levels of GLT-1, which protected the neurons and
      allowed them to survive 8-min ischemic insult that is usually lethal to neurons
      in the hippocampal CA1 subfield. 

PMID- 24442983
TI  - A new technique to investigate vestibulo-spinal reflexes.
AB  - Vestibulospinal reflexes can be elicited in humans by low amplitudes direct
      (galvanic) currents lasting tens of milliseconds and applied across the two
      mastoids bones, which can be delivered by particular stimulators. The stimulus
      induces a perception of body sway and a postural response appropriate to
      counteract the perceived sway. Both the direction of the perceived and induced
      body sway are modulated by the orientation of the head with respect to the body.
      This phenomenon is due to the fact that integration of vestibular and neck
      signals allows to correctly infer the direction of body sway from the
      labyrinthine input, which is instead related to direction of head motion. The
      modulation of stimulus-elicited body sway by neck rotation could be utilised for
      testing the effectiveness of neck proprioceptive signals in modifying the
      reference frame for labyrinthine signals from the head to the body. In the
      present experiments we showed that labyrinthine stimulation can be performed also
      by using train of pulses of 1 msec duration, which can be delivered by virtually
      all stimulators allowed for human use. Moreover, we developed a simple technique
      for visualising the time course of the changes in the direction of the postural
      response, based on the evaluation of the velocity vector of subject's centre of
      pressure. This method could be exploited in order to the test the efficacy of
      neck proprioceptive information in modifying the reference frame for processing
      vestibular signals in both physiological and pathological condition. 

PMID- 24442984
TI  - Excitotoxicity and Wallerian degeneration as a processes related to cell death in
      nervous system.
AB  - Cell death is one of the processes that are currently extensively studied. Beside
      the commonly used terminology regarding cell death, i.e. apoptosis, autophagy,
      necrosis, and cornification, in recent years there has been a growing number of
      additional definitions of this process, such as mitotic catastrophe, anoikis,
      entosis, paraptosis, pyroptosis, pyronecrosis, excitotoxicity, and Wallerian
      degeneration, which are described in 2009 by the Nomenclature Committee on Cell
      Death as atypical. The recent report of that Committee significantly alter the
      classification and nomenclature of the cell death processes, in which
      excitotoxicity and Wallerian degeneration have not been taken into account. Thus
      the present review describes excitotoxicity, and Wallerian degeneration, as two
      processes associated to cell death phenomena characteristic for nervous system.
      Excitotoxicity is a neuronal death caused by excessive, or prolonged activation
      of receptors for the excitatory amino acids. Depending on the intensity of the
      initiating stimulus, the excitotoxicity may overlap with other types of cell
      death such as apoptosis and necrosis. Wallerian degeneration is a process that
      results when a nerve fiber is cut or crushed, in which the part of the axon
      separated from the neuron's cell body degenerates distal to the injury. Wallerian
      degeneration is not a typical cell death mechanism, since neurons undergoing this
      process remain alive. 

PMID- 24442985
TI  - Interpreting the gene expression microarray results: a user-based experience.
AB  - In recent years many tools have been developed to cope with the interpretation of
      gene expression results from microarray experiments. The effectiveness of these
      tools largely depends on their ease of use by biomedical researchers. Tools based
      on effective computational methods, indeed, cannot be fully exploited by users if
      they are not supported by an intuitive interface, a large set of utilities and
      effective outputs. In this paper, 10 tools for the interpretation of gene
      expression microarray results have been tested on 11 microarray datasets and
      evaluated according to eight assessment criteria: 1. interface design and
      usability, 2. easiness of input submission, 3. effectiveness of output
      representation and 4. of the downloaded outputs, 5. possibility to submit
      multiple gene IDs, 6. sources of information, 7. provision of different
      statistical tests and 8. of multiple test correction methods. Strengths and
      weaknesses of each tool are highlighted to: a. provide useful tips to users
      dealing with the biological interpretation of microarray results; b. draw the
      attention of software developers on the usability of their tools.

PMID- 24442986
TI  - Using the proximal perforator-based anterolateral thigh flap from the same donor
      site to salvage the reconstruction after failure of the distal perforator-based
      anterolateral thigh flap.
AB  - We presented a patient who experienced the anterolateral thigh (ALT) flap failure
      but the reconstruction was successfully salvaged by harvesting a second ALT flap
      from the same donor site 2 days after the first reconstruction. A 47-year-old man
      received cancer ablation for right mouth floor squamous cell carcinoma. The
      resultant defect was planned to be reconstructed with the ALT flap. During the
      flap dissection, we identified three proximal cutaneous perforators originating
      from the transverse branch of the lateral circumflex femoral artery (t-LCFA) and
      two distal cutaneous perforators originating from the descending branch (d-LCFA).
      We harvested a skin flap based on the distal two perforators and divided the d
      LCFA just distal to the bifurcation of the d-LCFA and the t-LCFA. Unfortunately,
      the ALT flap showed venous congestion on postoperative day 2 and eventually
      failed. We harvested a second ALT flap from the same donor site based on the
      previously preserved perforators. The recovery course was smooth thereafter. We
      believe that the harvest of a second ALT flap from the same donor site may be an
      option, to avoid other donor site violation, in some patients who experienced the
      first flap loss. (c) 2014 Wiley Periodicals, Inc. Microsurgery 34:409-412, 2014. 

PMID- 24442987
TI  - Critical incidents related to opioid infusions in children: a five-year review
      and analysis.
AB  - PURPOSE: Opioids have a narrow therapeutic index and have the potential to cause
      significant harm. Developmental and pharmacogenetic factors put children, and
      especially infants, at increased risk of complications. We performed a
      retrospective root cause analysis to identify the factors associated with
      critical incidents in children receiving opioid infusions in a tertiary care
      children's hospital. METHODS: Following institutional ethical approval, we
      identified potential critical incidents during 2004 to 2009 from patient safety
      and pharmacy data. Patients' medical charts were reviewed and a timeline of
      events that occurred before, during, and following each incident was generated. A
      safety assessment code score was assigned to each incident according to its
      severity and probability of recurrence, and incidents with a score >= 8 were
      selected for root cause analysis. Root causes were identified and classified,
      formal causal statements were written, and action plans were recommended.
      RESULTS: One hundred and sixty-six medical charts were reviewed, and 58 of these
      included one (45/58) or more (13/58) relevant critical incidents. The resulting
      harms were of minor to moderate severity. Fourteen incidents were submitted for
      detailed analysis, from which 31 root causes were identified. The most frequent
      and significant root causes involved defects in pre-printed order sheets, lack of
      a nursing guidelines for infusions (rate, adjustment, weaning), and inadequate
      guidelines for monitoring and recording pain, vital signs, and arousal scores.
      DISCUSSION: The root causes of a range of critical incidents have been
      identified, and these have been used to generate recommendations for improving
      both patient safety and quality of analgesia for children receiving opioid
      infusions for acute pain management.

PMID- 24442988
TI  - From the Journal archives: Airway closure and lung volumes in surgical positions.
AB  - AUTHORS: Douglas B. Craig, W.M. Wahba, Hillary Don CITATION: Can Anaesth Soc J
      1971; 18: 92-9. PURPOSE: Surgery and anesthesia expose patients to moderate and
      sometimes extreme positioning changes that are often unphysiological. The purpose
      of this article is to highlight and contextualize a seminal study from the
      Journal archives that explores the effect of several commonly utilized surgical
      positions (supine, Trendelenburg and lithotomy) and age on basic lung volumes as
      well as the volume at which small airway closure (AC) (also known as closing
      volume [CV]) occurs. These factors were examined with the aim of determining
      which patient position variables could be of clinical significance to gas
      exchange in the perioperative period. PRINCIPAL FINDINGS: This work showed that
      supine positioning, when compared with the seated position, results in a decrease
      of all lung volumes and capacities, including functional residual capacity (FRC)
      and CV. Trendelenburg positioning further decreases FRC, with no further changes
      induced by lithotomy positioning. Age is a clinically important factor in AC,
      occurring within the tidal volume range at a lower age when supine as compared
      with the seated position. CONCLUSIONS: The work of Drs. D. Craig et al. published
      in the Journal more than 40 years ago was seminal to our understanding of how
      patient positioning has an important influence on lung volumes and on the age
      related relationship between FRC and CV.

PMID- 24442989
TI  - The effect of butylphthalide on the brain edema, blood-brain barrier of rats
      after focal cerebral infarction and the expression of Rho A.
AB  - The aim of this study was to explore the effect of butylphthalide on the brain
      edema, blood-brain barrier of rats of rats after focal cerebral infarction and
      the expression of Rho A. A total of 195 sprague-dawley male rats were randomly
      divided into control group, model group, and butylphthalide group (40 mg/kg, once
      a day, by gavage). The model was made by photochemical method. After surgery 3,
      12, 24, 72, and 144 h, brain water content was done to see the effect of
      butylphthalide for the cerebral edema. Evans blue extravasation method was done
      to see the changes in blood-brain barrier immunohistochemistry, and Western blot
      was done to see the expression of Rho A around the infarction. Compared with the
      control group, the brain water content of model group and butylphthalide group
      rats was increased, the permeability of blood-brain barrier of model group and
      butylphthalide group rats was increased, and the Rho A protein of model group and
      butylphthalide group rats was increased. Compared with the model group, the brain
      water content of butylphthalide group rats was induced (73.67 +/- 0.67 vs 74.14
      +/- 0.46; 74.89 +/- 0.57 vs 75.61 +/- 0.52; 77.49 +/- 0.34 vs 79.33 +/- 0.49;
      76.31 +/- 0.56 vs 78.01 +/- 0.48; 72.36 +/- 0.44 vs 73.12 +/- 0.73; P < 0.05),
      the permeability of blood-brain barrier of butylphthalide group rats was induced
      (319.20 +/- 8.11 vs 394.60 +/- 6.19; 210.40 +/- 9.56 vs 266.40 +/- 7.99; 188.00
      +/- 9.22 vs 232.40 +/- 7.89; 288.40 +/- 7.86 vs 336.00 +/- 6.71; 166.60 +/- 6.23
      vs 213.60 +/- 13.79; P < 0.05), and the Rho A protein of butylphthalide group
      rats was decreased (western blot result: 1.2230 +/- 0.0254 vs 1.3970 +/- 0.0276;
      1.5985 +/- 0.0206 vs 2.0368 +/- 0.0179; 1.4229 +/- 0.0167 vs 1.7930 +/-
      0.0158;1.3126 +/- 0.0236 vs 1.5471 +/- 0.0158; P < 0.05). The butylphthalide
      could reduce the brain edema, protect the blood-brain barrier, and decrease the
      expression of Rho A around the infarction.

PMID- 24442990
TI  - Correlation of matrix metalloproteinases-1 and tissue inhibitor of
      metalloproteinases-1 with patient age and grade of lumbar disk herniation.
AB  - The authors studied the nuclear magnetic resonance films and the expression of
      MMP-1 and TIMP-1 in disk specimens' of patients who had undergone operations for
      lumbar disk herniation. Forty-one lumbar disk patients were evaluated imaging for
      degenerative changes and their disk specimens immunohistochemical expression of
      MMP-1 and TIMP-1. The degree of degenerative changes was based on magnetic
      resonance imaging films. Sections of disk immunostained for MMP-1 and TIMP-1 were
      evaluated semiquantitatively. Patients were categorized in three age groups: <30
      years, from 30 to 60 years, and >60 years of age. The expressions of MMP-1 and
      TIMP-1 were related to patients' age and degree of degenerative changes. There
      were statistical differences in the expression of MMP-1 and TIMP-1 between the
      age and degree of degenerative changes groups. With the degree of degenerative
      changes, the expression of MMP-1 and TIMP-1 increased obviously. But in old age
      group, the expression of MMP-1/TIMP-1 was higher than the young groups. The
      expressions of MMP-1 and TIMP-1 were strongly correlated to the age and the
      degree of the degenerative changes. An important finding in this study is the
      unbalance of the expression of MMP-1 and TIMP-1 along with the growth of the age.

PMID- 24442991
TI  - Gradual and controlled decompression for brain swelling due to severe head
      injury.
AB  - Patients suffering from uncontrollable intracranial hypertension due to
      posttraumatic brain swelling (BS) generally either die or survive in an extremely
      disabled state. Decompressive craniectomy (DC) with dural augmentation may be the
      best method to assist these patients. However, the efficacy of DC on functional
      outcomes remains controversial. One of the factors contributing to poor outcomes
      could be intraoperative brain extrusion, which is an acute potential complication
      of DC. The authors have adopted a new surgical technique for traumatic BS that
      can prevent and control massive intraoperative BS (IOS). In the past 3 years, the
      authors have used a unique technique, called "gradual and controlled
      decompression", in the treatment of posttraumatic BS. This procedure consists of
      creating numerous small dural openings and removing clots; enlarging fenestration
      in the frontal and temporal basal regions to detect and treat brain contusion;
      making U-shaped, discontinuous, small dural incisions around the circumference of
      the craniotomy; and performing an augmentation duraplasty through the
      discontinuous small opening with dural prosthetic substances. This technique has
      been employed in 23 patients suffering from posttraumatic BS. In all cases, IOS
      was prevented and controlled through gradual stepwise decompression, and expanded
      duraplasty was performed successfully. This new surgical approach for
      posttraumatic BS can prevent severe extrusion of the brain through the craniotomy
      defect and allows the gradual and gentle release of the subdural space. Further
      clinical studies should be conducted to estimate the impact of this new technique
      on morbidity and mortality rates. 

PMID- 24442992
TI  - Oral hepatoprotective ability evaluation of purple sweet potato anthocyanins on
      acute and chronic chemical liver injuries.
AB  - In recent years, chemical liver injury cases increased significantly in Asian
      countries, and the imbalance in redox system was believed to be the main cause.
      Purple sweet potato anthocyanins (PSPA) have been shown to exert antioxidant
      activity and oxidative-stress-associated functional protein modulation through
      various signaling pathways, so it is considered to have the potential of liver
      injury preventive activity. In order to evaluate the hepatoprotective potency of
      PSPA according to its free radical scavenging and antioxidant effects, three
      acute chemical liver injury models were set up with ethanol, acetaminophen and
      carbon tetrachloride. PSPA at moderate and high doses obviously attenuated the
      tested serum biomarker levels and liver index in our experiments. Besides, one
      chronic liver injury model set up with carbon tetrachloride was also applied, in
      which PSPA was orally administrated after the liver damage had been formed. Both
      the serum biomarker levels and histopathological analysis showed that PSPA was
      able to attenuated chronic liver injury. Our experimental results demonstrated
      the potential of PSPA as an oral hepatoprotective agent against chemical liver
      injury from food plant. 

PMID- 24442993
TI  - A new technique for single-segment bone graft, decompression, and fusion in
      patients with C1/2 canal stenosis: technical note.

PMID- 24442994
TI  - Association of receptor activator of nuclear factor-kappaB ligand (RANKL) gene
      polymorphisms with the susceptibility to ankylosing spondylitis: a case-control
      study.
AB  - OBJECTIVES: To investigate the association between receptor activator of nuclear
      factor-kappaB ligand (RANKL) gene polymorphisms and the susceptibility to
      ankylosing spondylitis (AS) in a Chinese Han population. METHODS: Three hundred
      and fifty-two AS patients and 299 age- and gender-matched controls were recruited
      in this study. Peripheral blood samples were collected from all the subjects and
      the genomic DNA was then extracted. Three single nucleotide polymorphisms (SNPs)
      of the RANKL gene (rs2277438, rs7984870 and rs9533156) were genotyped using the
      TaqMan assay. The frequencies of alleles and genotypes were compared between AS
      patients and normal controls. RESULTS: The distributions of genotype frequencies
      in rs2277438 were significantly different between AS patients and normal controls
      (P < 0.05). The frequency of G allele of SNP rs2277438 in AS patients was
      significantly higher than that in normal controls (P < 0.05). The frequencies of
      genotypes with G allele (GG and AG) were significantly higher in AS patients when
      compared with normal controls (OR = 1.573, 95 % CI 1.151-2.150, P < 0.05).
      Neither the genotype frequencies nor the allele frequencies of rs7984870 and
      rs9533156 were found to be significantly different between AS patients and normal
      controls (P > 0.05). CONCLUSIONS: The current study demonstrated that SNP
      rs2277438 of the RANKL gene was associated with the susceptibility of AS in a
      Chinese Han population. Genotypes with G allele (GG and AG) were identified as
      the risk factors for the occurrence of AS.

PMID- 24442995
TI  - A novel modification of the Turing test for artificial intelligence and robotics
      in healthcare.
AB  - BACKGROUND: The increasing demands of delivering higher quality global healthcare
      has resulted in a corresponding expansion in the development of computer-based
      and robotic healthcare tools that rely on artificially intelligent technologies.
      The Turing test was designed to assess artificial intelligence (AI) in computer
      technology. It remains an important qualitative tool for testing the next
      generation of medical diagnostics and medical robotics. METHODS: Development of
      quantifiable diagnostic accuracy meta-analytical evaluative techniques for the
      Turing test paradigm. RESULTS: Modification of the Turing test to offer
      quantifiable diagnostic precision and statistical effect-size robustness in the
      assessment of AI for computer-based and robotic healthcare technologies.
      CONCLUSIONS: Modification of the Turing test to offer robust diagnostic scores
      for AI can contribute to enhancing and refining the next generation of digital
      diagnostic technologies and healthcare robotics.

PMID- 24442996
TI  - Transverse cervical and great auricular nerve distribution in the mandibular
      area: a study in human cadavers.
AB  - The angle of the jaw is innervated by the auricular branch of the superficial
      cervical plexus (SCP). Cervical cutaneous nerves of the CP carry the sensation
      from the antero-lateral cervical skin. It is clinically relevant to identify the
      cervical cutaneous nerve distribution and the nerve point using superficial
      landmarks but published studies describing the emerging patterns and cervical
      cutaneous nerve branch distributions in the mandible are rare. The overlap
      between the cervical and trigeminal and facial nerve distributions and
      anastomoses is highly variable. The objective of this study was to characterize
      the distribution of the SCP nerves in the different parts of the mandible. Two
      hundred and fifty fresh and formalin-fixed human cadaver heads were
      microdissected to observe the distribution of the transverse cervical (TCN) and
      great auricular (GAN) nerves. Two main groups (G1 and G2) based on the emergence
      of the TCN and GAN behind the posterior edge of the sternocleidomastoid muscle
      and three types (T1, T2, and T3) based on their distribution in the different
      mandibular parts were observed. Statistical analysis showed that parameters
      related to the mandibular side (P = 0.307), gender (P = 0.218), and group (P =
      0.111) did not influence the facial distribution of these nerves. The only
      parameter influencing the distribution was the type of nerve (GAN and TCN) (P <
      0.001). In the face, the SCP reached the mandible in 97% of cases, its
      distribution and extent were subject-dependent. These results confirmed that the
      SCP could supply accessory innervation to the mandible through the TCN.

PMID- 24442997
TI  - CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by
      SIRT1.
AB  - The protein deacetylase, sirtuin 1 (SIRT1), involved in regulating hepatic
      insulin sensitivity, shows circadian oscillation and regulates the circadian
      clock. Recent studies show that circadian misalignment leads to insulin
      resistance (IR); however, the underlying mechanisms are largely unknown. Here, we
      show that CLOCK and brain and muscle ARNT-like protein 1 (BMAL1), two core
      circadian transcription factors, are correlated with hepatic insulin sensitivity.
      Knockdown of CLOCK or BMAL1 induces hepatic IR, whereas their ectopic expression
      attenuates hepatic IR. Moreover, circadian change of insulin sensitivity is
      impaired in Clock mutant, liver-specific Bmal1 knockout (KO) or Sirt1 KO mice,
      and CLOCK and BMAL1 are required for hepatic circadian expression of SIRT1.
      Further studies show that CLOCK/BMAL1 binds to the SIRT1 promoter to enhance its
      expression and regulates hepatic insulin sensitivity by SIRT1. In addition,
      constant darkness-induced circadian misalignment in mice decreases hepatic BMAL1
      and SIRT1 levels and induces IR, which can be dramatically reversed by
      resveratrol. CONCLUSION: These findings offer new insights for coordination of
      the circadian clock and metabolism in hepatocytes by circadian regulation of
      hepatic insulin sensitivity via CLOCK/BMAL1-dependent SIRT1 expression and
      provide a potential application of resveratrol for combating circadian
      misalignment-induced metabolic disorders.

PMID- 24442998
TI  - From diagnosis through survivorship: health-care experiences of colorectal cancer
      survivors with ostomies.
AB  - PURPOSE: The journey from diagnosis through treatment to survivorship can be
      challenging for colorectal cancer (CRC) survivors with permanent ostomies.
      Memories of both the positive and negative health-care interactions can persist
      years after the initial diagnosis and treatment. The purpose of this paper is to
      describe the health-care experiences of long-term (>5 years) CRC survivors with
      ostomies. METHODS: Thirty-three CRC survivors with ostomies who were members of
      Kaiser Permanente, an integrated care organization, in Oregon, southwestern
      Washington and northern California participated in eight focus groups.
      Discussions from the focus groups were recorded, transcribed, and analyzed for
      potential categories and themes. RESULTS: Health-care-related themes described
      CRC survivors' experiences with diagnosis, treatment decision-making, initial
      experiences with ostomy, and survivorship. Participants discussed both positive
      and negative health-care-related experiences, including the need for continued
      access to trained nurses for ostomy self-care, access to peer support, and
      resources related to managing persistent, debilitating symptoms. CONCLUSIONS:
      Long-term CRC survivors with ostomies have both positive and negative health-care
      experiences, regardless of health-related quality of life (HRQOL) and gender.
      Long-term support mechanisms and quality survivorship care that CRC survivors
      with ostomies can access are needed to promote positive adjustments and improved
      HRQOL. The current literature in CRC survivorship suggests that HRQOL concerns
      can persist years after treatment completion. The coordination of care to manage
      persistent late- and long-term effects are still lacking for CRC survivors living
      with an ostomy. Findings from this qualitative analysis will aid in the
      development of support strategies that foster more positive adjustments for CRC
      survivors living with an ostomy and support their ongoing ostomy-related needs.

PMID- 24442999
TI  - Complementary and alternative medicine use and disclosure amongst Australian
      radiotherapy patients.
AB  - PURPOSE: Information on complementary and alternative medicine (CAM) use in
      Australian radiotherapy patients is sparse. This study investigated the type and
      prevalence of CAM amongst an Australian regional radiotherapy patient cohort and
      the disclosure of information to the consultant radiation oncologist. METHODS: A
      single hardcopy questionnaire survey was provided to patients regarding the use
      of CAM and discussion with the treating medical practitioner. The National Centre
      for Complementary and Alternative Medicine (NCCAM) classification was used to
      group responses. The study was open for a period of 4 months, and all patients on
      treatment during this period were approached. RESULTS: A total of 170
      questionnaires were distributed to eligible patients, and 152 patients returned a
      completed questionnaire (89.4 % response rate). Sixty-nine of the 152 patients
      (45.4 %) reported active CAM use. Of the 69 patients who used CAM, mind-body
      medicine (n = 54, 78.3 %) and biological-based therapies (n = 54, 78.3 %) were
      the commonest NCCAM group, whilst manipulative/body-based therapies (n = 44, 63.8
      %), whole medical systems (n = 7, 10.1 %) and energy therapies (n = 5, 7.2 %)
      were the least common. The most common therapies were vitamins and mineral
      supplementation (n = 33, 47.8 %) and massage therapy (n = 18, 26.1 %). Of note,
      only 29 participants stated that they had discussed CAM therapies with their
      radiation oncologist. CONCLUSIONS: CAM use was prevalent amongst cancer patients
      undergoing radiotherapy, but frequently not discussed with the treating radiation
      oncologist. Considering the high prevalence of CAM, further resources could be
      justifiably directed at providing this service for cancer patients to foster a
      more holistic approach to their care.

PMID- 24443000
TI  - Cancer-related fatigue: can it be due to adrenal suppression secondary to high
      dose steroids used as antiemetic?

PMID- 24443001
TI  - An extra dose of rituximab improves clinical response in rheumatoid arthritis
      patients with initial incomplete B cell depletion: a randomised controlled trial.
AB  - OBJECTIVES: Since clinical non-response to 2*1000 mg rituximab has previously
      been found to be associated with incomplete B cell depletion, we determined, in a
      randomised controlled proof of concept study, whether patients with initial
      incomplete B cell depletion would benefit from an additional infusion of
      rituximab at week 4. METHODS: Patients with active rheumatoid arthritis despite
      methotrexate received a first infusion of rituximab 1000 mg and were tested for
      persistent B cells using highly sensitive flow cytometry on day 15. All received
      a second infusion of 1 g (according to license), but patients with persistent B
      cells were subsequently randomised double-blind to receive, 2 weeks later, either
      a third infusion of 1000 mg rituximab or placebo. Clinical response was
      determined by European League Against Rheumatism (EULAR) and American College of
      Rheumatology (ACR) criteria. RESULTS: Baseline characteristics were balanced
      between groups. Treatment with 3*1000 mg rituximab resulted in significantly
      greater depletion (lower B cell and plasmablast numbers between 8 and 28 weeks)
      paralleled by significantly better EULAR and ACR20 response rates at 40 weeks
      (p=0.035 and p=0.027, respectively) and 52 weeks (p=0.021 and p=0.043,
      respectively) compared with 2*1000 mg. Immunoglobulin titres remained stable in
      both arms, and adverse event rates were balanced. CONCLUSIONS: In rituximab
      treated patients with incomplete B cell depletion (predictive of poor response),
      an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion
      and clinical responses than placebo with no worsening of safety. Degree of
      depletion is an important, but modifiable, determinant of response.

PMID- 24443002
TI  - In situ generation of cell-laden porous MMP-sensitive PEGDA hydrogels by gelatin
      leaching.
AB  - Proteolytically degradable poly(ethylene) glycol (PEG) hydrogels have been
      investigated as tissue engineering scaffolds; however, cell invasion and tissue
      regeneration are limited by the rate of cell-mediated degradation due to the
      small mesh size of the resultant crosslinked network. Gelatin leaching is
      combined with photopolymerization to form porous matrix-metalloproteinase (MMP)
      sensitive PEG scaffolds under cytocompatible conditions in the presence of cells.
      Gelatin leaching allows control over pore size and porosity through selectivity
      of gelatin bead particle size and porogen loading, respectively. Increases in
      porogen loading lead to increased porosity, decreased compressive modulus and
      degradation time, and enhanced proliferation of encapsulated vascular smooth
      muscle cells. 

PMID- 24443003
TI  - Modelling the impact of HIV on the populations of South Africa and Botswana.
AB  - We develop and use mathematical models that describe changes in the South African
      population over the last decades, brought on by HIV and AIDS. We do not model all
      the phases in HIV progression but rather, we show that a relatively simple model
      is sufficient to represent the data and allows us to investigate important
      aspects of HIV infection: firstly, we are able to investigate the effect of
      awareness on the prevalence of HIV and secondly, it enables us to make a
      comparison between South Africa and Botswana. A comparison is made between two
      models: a model that does not reflect awareness of the devastating impact of HIV
      and AIDS, and a model with an added psychological awareness factor. Both models
      are fitted to data that reflects the incidence of HIV and AIDS within South
      Africa. This allows us to examine the impact of psychological awareness. We show
      that inclusion of the effect of awareness is absolutely necessary to arrive at a
      model description that satisfactorily fits the available HIV and AIDS data for
      South Africa. We also show that a relatively simple modelling of awareness (as
      opposed to more complex mathematical techniques that have been used in past
      studies) is sufficient to accurately describe the observed patterns in the data.
      Even though awareness alone is not sufficient to eradicate any disease and other
      control strategies should be explored and implemented concurrently with
      educational campaigns, we are able to conclude (through thorough model analyses
      procedures) that the current level of awareness in South Africa is far below the
      level that is effectively required to eradicate HIV from the South African
      population. The awareness model is also fitted to HIV-related data for Botswana
      and we compare the results with the South African case. Though the effect of
      awareness is currently estimated at a much higher level in Botswana, other
      factors such as poorer health care and cultural differences may play a role in
      limiting the ability of awareness to combat HIV in Botswana. 

PMID- 24443004
TI  - Canine epidermal neural crest stem cells: characterization and potential as
      therapy candidate for a large animal model of spinal cord injury.
AB  - The discovery of multipotent neural crest-derived stem cells, named epidermal
      neural crest stem cells (EPI-NCSC), that persist postnatally in an easy-to-access
      location-the bulge of hair follicles-opens a spectrum of novel opportunities for
      patient-specific therapies. We present a detailed characterization of canine EPI
      NCSC (cEPI-NCSC) from multiple dog breeds and protocols for their isolation and
      ex vivo expansion. Furthermore, we provide novel tools for research in canines,
      which currently are still scarce. In analogy to human and mouse EPI-NCSC, the
      neural crest origin of cEPI-NCSC is shown by their expression of the neural crest
      stem cell molecular signature and other neural crest-characteristic genes.
      Similar to human EPI-NCSC, cEPI-NCSC also expressed pluripotency genes. We
      demonstrated that cEPI-NCSC can generate all major neural crest derivatives. In
      vitro clonal analyses established multipotency and self-renewal ability of cEPI
      NCSC, establishing cEPI-NCSC as multipotent somatic stem cells. A critical
      analysis of the literature on canine spinal cord injury (SCI) showed the need for
      novel treatments and suggested that cEPI-NCSC represent viable candidates for
      cell-based therapies in dog SCI, particularly for chondrodystrophic dogs. This
      notion is supported by the close ontological relationship between neural crest
      stem cells and spinal cord stem cells. Thus, cEPI-NCSC promise to offer not only
      a potential treatment for canines but also an attractive and realistic large
      animal model for human SCI. Taken together, we provide the groundwork for the
      development of a novel cell-based therapy for a condition with extremely poor
      prognosis and no available effective treatment. 

PMID- 24443005
TI  - Concise review: parthenote stem cells for regenerative medicine: genetic,
      epigenetic, and developmental features.
AB  - Embryonic stem cells (ESCs) have the potential to provide unlimited cells and
      tissues for regenerative medicine. ESCs derived from fertilized embryos, however,
      will most likely be rejected by a patient's immune system unless appropriately
      immunomatched. Pluripotent stem cells (PSCs) genetically identical to a patient
      can now be established by reprogramming of somatic cells. However, practical
      applications of PSCs for personalized therapies are projected to be unfeasible
      because of the enormous cost and time required to produce clinical-grade cells
      for each patient. ESCs derived from parthenogenetic embryos (pESCs) that are
      homozygous for human leukocyte antigens may serve as an attractive alternative
      for immunomatched therapies for a large population of patients. In this study, we
      describe the biology and genetic nature of mammalian parthenogenesis and review
      potential advantages and limitations of pESCs for cell-based therapies. 

PMID- 24443006
TI  - Three-year outcomes of cultured limbal epithelial allografts in aniridia and
      Stevens-Johnson syndrome evaluated using the Clinical Outcome Assessment in
      Surgical Trials assessment tool.
AB  - Limbal stem cell deficiency (LSCD) is an eye disorder in which the stem cells
      responsible for forming the surface skin of the cornea are destroyed by disease.
      This results in pain, loss of vision, and a cosmetically unpleasant appearance.
      Many new treatments, including stem cell therapies, are emerging for the
      treatment of this condition, but assessment of these new technologies is severely
      hampered by the lack of biomarkers for this disease or validated tools for
      assessing its severity. The aims of this study were to design and test the
      reliability of a tool for grading LSCD, to define a set of core outcome measures
      for use in evaluating treatments for this condition, and to demonstrate their
      utility. This was achieved by using our defined outcome set (which included the
      Clinical Outcome Assessment in Surgical Trials of Limbal stem cell deficiency
      [COASTL] tool) to evaluate the 3-year outcomes for allogeneic ex vivo cultivated
      limbal epithelial transplantation (allo-CLET) in patients who had bilateral total
      LSCD secondary to aniridia or Stevens-Johnson syndrome. The results demonstrate
      that our new grading tool for LSCD, the COASTL tool, is reliable and repeatable,
      and that improvements in the biomarkers used in this tool correlate positively
      with improvements in visual acuity. The COASTL tool showed that following allo
      CLET there was a decrease in LSCD severity and an increase in visual acuity up to
      12 months post-treatment, but thereafter LSCD severity and visual acuity
      progressively deteriorated. 

PMID- 24443007
TI  - Help seeking in older Asian people with dementia in Melbourne: using the Cultural
      Exchange Model to explore barriers and enablers.
AB  - The prevalence of dementia is increasing in Australia. Limited research is
      available on access to Cognitive Dementia and Memory Services (CDAMS) for people
      with dementia from Culturally and Linguistically Diverse (CALD) communities. This
      study aimed to determine the barriers and enablers to accessing CDAMS for people
      with dementia and their families of Chinese and Vietnamese backgrounds.
      Consultations with community members, community workers and health professionals
      were conducted using the "Cultural Exchange Model" framework. For carers,
      barriers to accessing services included the complexity of the health system, lack
      of time, travel required to get to services, language barriers, interpreters and
      lack of knowledge of services. Similarly, community workers and health
      professionals identified language, interpreters, and community perceptions as key
      barriers to service access. Strategies to increase knowledge included providing
      information via radio, printed material and education in community group
      settings. The "Cultural Exchange Model" enabled engagement with and modification
      of the approaches to meet the needs of the targeted CALD communities. 

PMID- 24443008
TI  - Editorial note.

PMID- 24443009
TI  - Ecophysiological aspects of biomass production in higher plants.
AB  - Photosynthesis as a cosmic process of local entropy decrease is the basic
      phenomenon for life on Earth. Biomass production is energetically understood as a
      long-term storage of hydrogen. Endogeneously, the hierarchy of energy storage
      begins with the electric and proton gradient across the thylakoid membrane. At
      all higher levels of energy-converting system, efficiency is determined by the
      interactions between the autotrophic and heterotrophic part of the studied
      biosystem. Specially, the regulatory function of anabolic and catabolic reduction
      charge is discussed. From the frame of exogeneous factors, the action of calcium
      in connection with calmodulin is described as a second messenger.Summarizing, the
      findings are integrated into the energy-overflow concept in which the loss terms
      act as system stabilizers especially under injuring conditions. 

PMID- 24443010
TI  - Effects of winter stress on photosynthetic electron transport and energy
      distribution between the two photosystems of pine as assayed by chlorophyll
      fluorescence kinetics.
AB  - The fluorescence kinetics of both intact needles and isolated chloroplasts of
      summer active and winter stressed Pinus sylvestris were measured at both room
      temperature and 77 K. It was confirmed that winter stress inhibited the
      photochemical capacity of photosystem II but also that winter stress caused the
      strongest inhibition of the electron transport at the site where the
      plastoquinone pool is reduced. Parallel analyses of the fluorescence
      characteristics of photosystem II (F693) and photosystem I (F729) during
      photosystem II trap closure furthermore revealed that the yield of spillover of
      excitation energy from photosystem II to photosystem I decreased upon winter
      stress. We suggest that this is because of an increased radiationless decay of
      excitation energy both at the reaction center and antennae levels of photosystem
      II. There is, however, also a possibility that the decreased yield of spill-over
      is accentuated by a partial detachment of the light harvesting chlorophyll a/b
      complex from photosystem II upon winter stress. 

PMID- 24443011
TI  - Inhibition of photosynthesis by heavy metals.
AB  - Inhibition of photosynthesis by heavy metals is well documented. In this review
      the results are compared between in vitro experiments on isolated systems
      (chloroplasts, enzymes -.), experiments on excised leaves and intact plants and
      algae in vivo. In vitro experiments suggest potential sites of heavy metal
      interaction with photosynthesis at several levels of organisation, which are not
      necessarily confirmed in vivo. Analytical data on subcellular heavy metal level
      are generally missing to discuss their mechanism of action in the intact
      organism. In the field factors such as soil characteristics and air pollution
      have to be taken into account for assessing the mechanism of action of heavy
      metals on photosynthesis in plants, growing in a polluted erea. 

PMID- 24443012
TI  - Ribulose bisphosphate carboxylase capacity and chlorophyll content in developing
      seedlings of Chenopodium rubrum L. growing under light of different qualities and
      fluence rates.
AB  - In order to evaluate the aclimation of Chenopodium seedlings to different quantum
      fluence rates of R and BL, kinetics of Rubisco capacity, Chl content and
      chloroplast structure were studied. Under monochromatic light photoreceptors are
      stimulated selectively and their influence on biosynthetis capacities during
      chloroplast development can be studied.R irradiations saturate Rubisco capacity
      even at the lowest quantum fluence rates applied, whereas Chl a+b synthesis
      depends strongly upon fluence rate of R. Under BL irradiations, both Rubisco
      capacity and Chl content are fluence rate dependent. R irradiations favour Chl b
      synthesis relative to Chl a, whereas under BL Chl a content is high relative to
      Chl b. Under R irradiation Pfr is the main photoreceptor involved in regulation
      of Rubisco capacity whereas under BL a specific BL absorbing photoreceptor may
      control the response. From the fluence rate dependency under BL irradiations it
      is concluded that the blue region of the day light spectrum may be the sensor for
      monitoring fluence rate and causing the characteristic changes in shade and
      high/low WL adaptation with respect to Rubisco levels in Chenopodium. 

PMID- 24443013
TI  - Studies on 9-amino-6-chloro-2-methoxy acridine fluorescence quenching and
      enhancement in relation to energy transduction in spheroplasts and intact cells
      of the cyanobacterium Plectonema boryanum.
AB  - The fluorescent probe 9-amino-6-chloro-2-methoxy acridine was used to study the
      energy transduction in the thylakoid and cell membranes of the cyanobacterium
      Plectonema boryanum. Apart from light-driven electron transfer, the dark
      endogenous respiration also leads to energization resulting in an ACMA
      fluorescence response, that is sensitive to the electron flow inhibitor 2, 5
      dibromo-3-methyl-6-isopropyl-p-benzoquinone, to the energy transfer inhibitors
      dicyclohexylcarbodiimide and venturicidine and to the uncoupler 5-chloro-3-t
      butyl-2'-chloro-4'-nitrosalicylanilide.In spheroplasts, in which the cell
      membranes have lost their capacity to maintain a proton gradient, the respiration
      and light-induced ACMA fluorescence changes (quenching) are similar to those in
      chloroplasts. In intact cells a combination of reversible quenching and
      enhancement of ACMA fluorescence was found. This dualistic behaviour is
      supposedly caused by an opposite orientation of the thylakoid and cell membranes.
      ACMA quenching at the level of the thylakoids was obtained either by respiratory
      or photosynthetic electron transfer and gave similar responses to those obtained
      in the spheroplasts. The slower ACMA fluorescence enhancement, only observed in
      cells with intact cell membranes, also evoked by both respiration and light
      induced energization is sensitive to the compounds mentioned above and in
      addition to KCN.Our results support the view [8] that dark oxidation of
      substrates by O2 proceeds via the thylakoid membrane and terminates at a CN(-)
      sensitive oxidase located in the cell membrane which requires the involvement of
      a mobile cytoplasmic redox mediator. 

PMID- 24443014
TI  - Effect of water stress on photosynthesis and in vitro activities of the PCR cycle
      enzymes in pigeonpea (Cajanus cajan L.).
AB  - Leaf water potential was decreased by withholding irrigation to provide three
      levels of stress described as mild ({ie69-1}) moderate ({ie69-2}) and severe
      ({ie69-3}). The specific activity of NADP linked glyceraldehyde-3-phosphate
      dehydrogenase, phosphoglycerate kinase, aldolase, phosphogluco-isomerase and RuBP
      carboxylase decreased under mild stress, but the activity of phosphoglucomutase
      showed an increase whilst ribulose-5-phosphate kinase was least affected. With
      further decrease in water potential, the activity of NADP linked glyceraldehyde-3
      phosphate dehydrogenase and aldolase showed a decrease, whereas, the activities
      of fructose-1,6-bisphosphatase, phosphoglycerate kinase, phosphogulcomutase and
      RuBP carboxylase increased. Net CO2 fixation decreased sharply with stress,
      whereas, respiration and photorespiration increased in moderate stress, but
      decreased under severe stress. Stomatal resistance also increased with decrease
      in water potential. It seems that in vitro enzyme activities of PCR cycle are not
      responsible for decreased photosynthesis in pigeonpea under short term water
      stress. 

PMID- 24443015
TI  - Photosynthesis, water use and growth of a C4 grass stand at high CO 2
      concentration.
AB  - Leaf photosynthesis rate of the C4 species Paspalum plicatulum Michx was
      virtually CO2-saturated at normal atmospheric CO2 concentration but transpiration
      decreased as CO2 was increased above normal concentrations thereby increasing
      transpiration efficiency. To test whether this leaf response led growth to be CO2
      sensitive when water supply was restricted, plants were grown in sealed pots of
      soil as miniature swards. Water was supplied either daily to maintain a constant
      water table, or at three growth restricting levels on a 5-day drying cycle.
      Plants were either in a cabinet with normal air (340 MUmol (CO2) mol(-1) (air))
      or with 250 MUmol mol(-1) enrichment. Harvesting was by several cycles of
      defoliation.With abundant water supply high CO2 concentration did not cause
      increased growth, but it did not cause an increase in growth over a wide range of
      growth-limiting water supplies either. Only when water supply was less than 30
      50% of the amount used by the stand with a water-table was there evidence that
      dry weight growth was enhanced by high CO2. In addition, with successive
      regrowth, the enhancing effect under a regime of minimal water allocations,
      became attenuated. Examination of leaf gas exchange, growth and water use data
      showed that in the long term stomatal conductance responses were of little
      significance in matching plant water use to low water allocation; regulation of
      leaf area was the mechanism through which consumption matched supply. Since high
      CO2 effects operate principally via stomatal conductance in C4 species, we
      postulate that for this species higher CO2 concentrations expected globally in
      future will not have much effect on long term growth. 

PMID- 24443016
TI  - Effects of proteinase K on the energy transfer between phycobiliproteins in
      phycobilisomes.
AB  - Spectral changes in fluorescence of phycobilisomes (PBS) of A. variabilis treated
      with proteinase K were studied at room and liquid nitrogen temperature. In
      control PBS, the relative yield of 77 K fluorescence of F686 was very high, and
      those of F655 and F666 were low. In PBS treated with proteinase K for less than 1
      h, F686 decreased, and F655 and F666 increased. In PBS treated with proteinase K
      for 2 h, F655 was the main peak of fluorescence emission, F686 was the second
      peak, the fluorescence emission peak of F666 disappeared. In PBS treated with
      proteinase K for more than 8 h, F655 showed only one fluorescence emission
      peak.We suggested that phycobiliporteins in the PBS of A. variabilis constitute
      an energy transfer chain, shown as follows:{fx91-1}The linkages between APC and
      APC-B, C-PC and APC, and C-PC and APC-B had different sensitivity towards
      proteinase K. 

PMID- 24443017
TI  - Introduction.

PMID- 24443018
TI  - Structure, physiology, and biochemistry of collagens.
AB  - Tendons and ligaments are connective tissues that guide motion, share loads, and
      transmit forces in a manner that is unique to each as well as the anatomical site
      and biomechanical stresses to which they are subjected. Collagens are the major
      molecular components of both tendons and ligaments. The hierarchical structure of
      tendon and its functional properties are determined by the collagens present, as
      well as their supramolecular organization. There are 28 different types of
      collagen that assemble into a variety of supramolecular structures. The assembly
      of specific supramolecular structures is dependent on the interaction with other
      matrix molecules as well as the cellular elements. Multiple suprastructural
      assemblies are integrated to form the functional tendon/ligament. This chapter
      begins with a discussion of collagen molecules. This is followed by a definition
      of the supramolecular structures assembled by different collagen types. The
      general principles involved in the assembly of collagen-containing
      suprastructures are presented focusing on the regulation of tendon collagen
      fibrillogenesis. Finally, site-specific differences are discussed. While
      generalizations can be made, differences exist between different tendons as well
      as between tendons and ligaments. Compositional differences will impact structure
      that in turn will determine functional differences. Elucidation of the unique
      physiology and pathophysiology of different tendons and ligaments will require an
      appreciation of the role compositional differences have on collagen
      suprastructural assembly, tissue organization, and function. 

PMID- 24443019
TI  - Basic components of connective tissues and extracellular matrix: elastin,
      fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and
      thrombospondins.
AB  - Collagens are the most abundant components of the extracellular matrix and many
      types of soft tissues. Elastin is another major component of certain soft
      tissues, such as arterial walls and ligaments. Many other molecules, though lower
      in quantity, function as essential components of the extracellular matrix in soft
      tissues. Some of these are reviewed in this chapter. Besides their basic
      structure, biochemistry and physiology, their roles in disorders of soft tissues
      are discussed only briefly as most chapters in this volume deal with relevant
      individual compounds. Fibronectin with its muldomain structure plays a role of
      "master organizer" in matrix assembly as it forms a bridge between cell surface
      receptors, e.g., integrins, and compounds such collagen, proteoglycans and other
      focal adhesion molecules. It also plays an essential role in the assembly of
      fibrillin-1 into a structured network. Laminins contribute to the structure of
      the extracellular matrix (ECM) and modulate cellular functions such as adhesion,
      differentiation, migration, stability of phenotype, and resistance towards
      apoptosis. Though the primary role of fibrinogen is in clot formation, after
      conversion to fibrin by thrombin, it also binds to a variety of compounds,
      particularly to various growth factors, and as such fibrinogen is a player in
      cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer
      of the monomeric soluble precursor tropoelastin, is the main component of elastic
      fibers in matrix tissue where it provides elastic recoil and resilience to a
      variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate
      activity of TGFbetas through their association with fibrillin microfibrils.
      Elastin also plays a role in cell adhesion, cell migration, and has the ability
      to participate in cell signaling. Mutations in the elastin gene lead to cutis
      laxa. Fibrillins represent the predominant core of the microfibrils in elastic as
      well as non-elastic extracellular matrixes, and interact closely with
      tropoelastin and integrins. Not only do microfibrils provide structural integrity
      of specific organ systems, but they also provide a scaffold for elastogenesis in
      elastic tissues. Fibrillin is important for the assembly of elastin into elastic
      fibers. Mutations in the fibrillin-1 gene are closely associated with Marfan
      syndrome. Fibulins are tightly connected with basement membranes, elastic fibers
      and other components of extracellular matrix and participate in formation of
      elastic fibers. Tenascins are ECM polymorphic glycoproteins found in many
      connective tissues in the body. Their expression is regulated by mechanical
      stress both during development and in adulthood. Tenascins mediate both
      inflammatory and fibrotic processes to enable effective tissue repair and play
      roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and
      recovery of musculo-tendinous tissue. One of the roles of thrombospondin 1 is
      activation of TGFbeta. Increased expression of thrombospondin and TGFbeta
      activity was observed in fibrotic skin disorders such as keloids and scleroderma.
      Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily
      present in the cartilage. High levels of COMP are present in fibrotic scars and
      systemic sclerosis of the skin, and in tendon, especially with physical activity,
      loading and post-injury. It plays a role in vascular wall remodeling and has been
      found in atherosclerotic plaques as well. 

PMID- 24443020
TI  - Proteoglycans and diseases of soft tissues.
AB  - Proteoglycans consist of a protein core to which at least one glycosaminoglycan
      chain is attached. They play important roles in the physiology and biomechanical
      function of tendons, ligaments and cardiovascular system through their
      involvement in regulation of assembly and maintenance of extracellular matrix,
      and as they participate in cell proliferation through their interactions with
      growth factors. They can be divided into two main groups of small and large
      proteoglycans. The small proteoglycans are also known as small leucine-rich
      proteoglycans (or SLRPs) which are encoded by 17 genes and are further
      subclassified into Classes I-V. Several members of Class I and II, such as
      decorin and biglycan from Class I, and Class II fibromodulin and lumican, are
      known to regulate collagen fibrillogenesis. Decorin limits the diameter of
      collagen fibrils during fibrillogenesis. The function of biglycan in
      fibrillogenesis is similar to that of decorin. Though biomechanical function of
      tendon is compromised in decorin-deficient mice, decorin can substitute for lack
      of biglycan in biglycan-deficient mice. New data also indicate an important role
      for biglycan in disorders of the cardiovascular system, including aortic valve
      stenosis and aortic dissection. Two members of the Class II of SLRPs,
      fibromodulin and lumican bind to the same site within the collagen molecule and
      can substitute for each other in fibromodulin- or lumican-deficient mice.Aggrecan
      and versican are the major representatives of the large proteoglycans. Though
      they are mainly found in the cartilage where they provide resilience and
      toughness, they are also present in tensile portions of tendons and, in slightly
      different biochemical form in fibrocartilage. Degradation with aggrecanase is
      responsible for the appearance of different forms of aggrecan and versican in
      different parts of the tendon where these cleaved forms play different roles. In
      addition, they are important components of the ventricularis of cardiac valves.
      Mutations in the gene for versican or in the gene for elastin (which binds to
      versican) lead to severe disruptions of normal developmental of the heart at
      least in mice. 

PMID- 24443021
TI  - Advances in the use of growth factors for treatment of disorders of soft tissues.
AB  - Repair and healing of injured and diseased tendons have been traditionally
      fraught with apprehension and difficulties, and often lead to rather
      unsatisfactory results. The burgeoning research field of growth factors has
      opened new venues for treatment of tendon disorders and injuries, and possibly
      for treatment of disorders of the aorta and major arteries as well. Several
      chapters in this volume elucidate the role of transforming growth factor beta in
      pathogenesis of several heritable disorders affecting soft tissues, such as
      aorta, cardiac valves, and tendons and ligaments. Several members of the bone
      morphogenetic group either have been approved by the FDA for treatment of non
      healing fractures or have been undergoing intensive clinical and experimental
      testing for use in healing of bone fractures and tendon injuries. Because FGFs
      are involved in embryonic development of tendons and muscles among other tissues
      and organs the hope is that their testing would lead to the development of some
      new treatment strategies providing that we can control angiogenicity of these
      growth factors. The problem, or rather question regarding practical use of IGF-I
      in tendon repair is whether IGF-I acts independently or under the guidance of
      growth hormone. FGF2 or PDGF alone or in combination with IGF-I stimulated
      regeneration of periodontal ligament, a matter of importance in Marfan patients
      with periodontitis. In contrast, VEGF appears to have rather deleterious effect
      on experimental tendon healing, perhaps because of its angiogenic activity and
      stimulation of matrix metalloproteinases, proteases whose increased expression
      has been documented in a variety of ruptured tendons. Other modalities, such as
      local administration of platelet-rich plasma (PRP) and/or of mesenchymal stem
      cells have been explored extensively in tendon healing. Though treatment with PRP
      and mesenchymal stem cells has met with some success in horses (who experience a
      lot of tendon injuries and other tendon problems), the use of PRP and mesenchymal
      stem cells in people has been more problematic and requires more studies before
      PRP and mesenchymal stem cells can become reliable tools in management of soft
      tissue injuries and disorders. 

PMID- 24443022
TI  - Clinical, diagnostic, and therapeutic aspects of the Marfan syndrome.
AB  - Marfan syndrome (MFS) is a relatively common and often lethal disease of
      connective tissue. Medical, surgical and basic research advances over the last
      two decades have had a major positive impact on the clinical management of MFS
      patients. Life expectancy has increased significantly, more discriminating
      diagnostic criteria have been developed, a number of new clinical entities have
      been recognized, and exciting opportunities for drug-based therapy have emerged.
      Despite such a remarkable progress, MFS diagnosis remains difficult and aortic
      disease progression is very heterogeneous and clinical outcome is unpredictable.
      Ongoing research efforts are therefore exploiting animal models of MFS to
      identify novel diagnostic and prognostic biomarkers, genetic, epigenetic and
      environmental modifiers and druggable biological targets. 

PMID- 24443023
TI  - Loeys-Dietz syndrome.
AB  - Loeys-Dietz syndrome is an autosomal dominant aortic aneurysm syndrome
      characterized by multisystemic involvement. The most typical clinical triad
      includes hypertelorism, bifid uvula or cleft palate and aortic aneurysm with
      tortuosity. Natural history is significant for aortic dissection at smaller
      aortic diameter and arterial aneurysms throughout the arterial tree. The genetic
      cause is heterogeneous and includes mutations in genes encoding for components of
      the transforming growth factor beta (TGFbeta) signalling pathway: TGFBR1, TGFBR2,
      SMAD3 and TGFB2. Despite the loss of function nature of these mutations, the
      patient-derived aortic tissues show evidence of increased (rather than decreased)
      TGFbeta signalling. These insights offer new options for therapeutic
      interventions. 

PMID- 24443025
TI  - The Ehlers-Danlos syndrome.
AB  - The Ehlers-Danlos Syndromes comprise a heterogeneous group of diseases, which are
      characterized by fragility of the soft connective tissues and widespread
      manifestations in skin, ligaments and joints, blood vessels and internal organs.
      The clinical spectrum varies from mild skin and joint hyperlaxity to severe
      physical disability and life-threatening vascular complications. The current
      Villefranche classification recognizes six subtypes, most of which are linked to
      mutations in one of the genes encoding fibrillar collagen proteins or enzymes
      involved in post-translational modification of these proteins. Establishing the
      correct EDS subtype has important implications for genetic counselling and
      management and is supported by specific biochemical and molecular investigations.
      Over the last years, the characterisation of several new EDS variants has
      broadened insights into the molecular pathogenesis of EDS by implicating genetic
      defects in the biosynthesis of other extracellular matrix molecules, such as
      proteoglycans and tenascin-X, or genetic defects in molecules involved in
      intracellular trafficking, secretion and assembly of extracellular matrix
      proteins. 

PMID- 24443026
TI  - Ehlers-Danlos syndrome associated with glycosaminoglycan abnormalities.
AB  - Ehlers-Danlos syndrome (EDS) is a genetically and clinically heterogeneous group
      of connective tissue disorders that typically present with skin
      hyperextensibility, joint hypermobility, and tissue fragility. The major cause of
      EDS appears to be impaired biosynthesis and enzymatic modification of collagen.
      In this chapter, we discuss two types of EDS that are associated with
      proteoglycan abnormalities: the progeroid type of EDS and dermatan 4-O
      sulfotransferase 1 (D4ST1)-deficient EDS. The progeroid type of EDS is caused by
      mutations in B4GALT7 or B3GALT6, both of which encode key enzymes that initiate
      glycosaminoglycan (GAG) synthesis. D4ST1-deficient EDS is caused by mutations in
      CHST14, which encodes an enzyme responsible for post-translational modification
      of GAG. The clinical and molecular characteristics of both types of EDS are
      described in this chapter. 

PMID- 24443027
TI  - Cutis Laxa.
AB  - Cutis laxa is an inherited or acquired disease characterized by redundant,
      sagging and inelastic skin. In inherited cutis laxa an abnormal synthesis of
      extracellular matrix proteins occurs due to genetic defects coding for diverse
      extracellular matrix components. Recently, different inborn errors of metabolism
      have been found to be associated with cutis laxa as well. In some of these
      metabolic conditions the pathomechanism of cutis laxa remains unknown. Cutis laxa
      can be inherited in an autosomal dominant, autosomal recessive and X-linked
      recessive inheritance pattern. Besides the skin abnormalities, in most inherited
      forms multiple organ systems are involved, leading to a severe, in some forms
      even lethal, multisystem disorder. To date no effective treatment is available
      for cutis laxa. This chapter focuses on inherited forms of cutis laxa, offering a
      practical guideline for clinicians, biochemist and geneticist to diagnose and
      differentiate between the different forms of cutis laxa, and providing a concise
      theoretical reference. 

PMID- 24443024
TI  - Connective tissue disorders and cardiovascular complications: the indomitable
      role of transforming growth factor-beta signaling.
AB  - Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable
      connective tissue disorders that cosegregate with a similar pattern of
      cardiovascular defects (thoracic aortic aneurysm, mitral valve
      prolapse/regurgitation, and aortic root dilatation with regurgitation). This
      pattern of cardiovascular defects appears to be expressed along a spectrum of
      severity in many heritable connective tissue disorders and raises suspicion of a
      relationship between the normal development of connective tissues and the
      cardiovascular system. Given the evidence of increased transforming growth factor
      beta (TGF-beta) signaling in MFS and LDS, this signaling pathway may represent
      the common link in this relationship. To further explore this hypothetical link,
      this chapter will review the TGF-beta signaling pathway, heritable connective
      tissue syndromes related to TGF-beta receptor (TGFBR) mutations, and discuss the
      pathogenic contribution of TGF-beta to these syndromes with a primary focus on
      the cardiovascular system. 

PMID- 24443028
TI  - Collagen type VI myopathies.
AB  - Mutations in each of the three collagen VI genes COL6A1, COL6A2 and COL6A3 cause
      two main types of muscle disorders: Ullrich congenital muscular dystrophy, a
      severe phenotype, and a mild to moderate phenotype Bethlem myopathy. Recently,
      two additional phenotypes, including a limb-girdle muscular dystrophy phenotype
      and an autosomal recessive myosclerosis reported in one family with mutations in
      COL6A2 have been reported. Collagen VI is an important component of the
      extracellular matrix which forms a microfibrillar network that is found in close
      association with the cell and surrounding basement membrane. Collagen VI is also
      found in the interstitial space of many tissues including muscle, tendon, skin,
      cartilage, and intervertebral discs. Thus, collagen VI mutations result in
      disorders with combined muscle and connective tissue involvement, including
      weakness, joint laxity and contractures, and abnormal skin findings.In this
      review we highlight the four recognized clinical phenotypes of collagen VI
      related - myopathies; Ullrich congenital muscular dystrophy (UCMD), Bethlem
      myopathy (BM), autosomal dominant limb-girdle muscular dystrophy phenotype and
      autosomal recessive myosclerosis. We discuss the diagnostic criteria of these
      disorders, the molecular pathogenesis, genetics, treatment, and related
      disorders. 

PMID- 24443029
TI  - Mouse models in tendon and ligament research.
AB  - Mutant mouse models are valuable resources for the study of tendon and ligament
      biology. Many mutant mouse models are used because their manifested phenotypes
      mimic clinical pathobiology for several heritable disorders, such as Ehlers
      Danlos Syndrome and Osteogenesis Imperfecta. Moreover, these models are helpful
      for discerning roles of specific genes in the development, maturation, and repair
      of musculoskeletal tissues. There are several categories of genes with essential
      roles in the synthesis and maintenance of tendon and ligament structures. The
      form and function of these tissues depend highly upon fibril-forming collagens,
      the primary extracellular macromolecules of tendons and ligaments. Models for
      these fibril-forming collagens, as well as for regulatory molecules like FACITs
      and SLRPs, are important for studying fibril assembly, growth, and maturation.
      Additionally, mouse models for growth factors and transcription factors are
      useful for defining regulation of cell proliferation, cell differentiation, and
      cues that stimulate matrix synthesis. Models for membrane-bound proteins assess
      the roles of cell-cell communication and cell-matrix interaction. In some cases,
      special considerations need to be given to spatio-temporal control of a gene in a
      model. Thus, conditional and inducible mouse models allow for specific regulation
      of genes of interest. Advances in mouse models have provided valuable tools for
      gaining insight into the form and function of tendons and ligaments. 

PMID- 24443030
TI  - Connective tissue disorders in domestic animals.
AB  - Though soft tissue disorders have been recognized and described to some detail in
      several types of domestic animals and small mammals for some years, not much
      progress has been made in our understanding of the biochemical basis and
      pathogenesis of these diseases in animals. Ehlers-Danlos syndrome described in
      dogs already in 1943 and later in cats affects mainly skin in these animals. The
      involved skin is thin and hyperextensible with easily inflicted injuries
      resulting in hemorrhagic wounds and atrophic scars. Joint laxity and dislocation
      common in people are less frequently found in dogs. No systemic complications,
      such as organ rupture or cardiovascular problems which have devastating
      consequences in people have been described in cats and dogs. The diagnosis is
      based on clinical presentation and on light or electron microscopic features of
      disorganized and fragmented collagen fibrils. Several cases of bovine and ovine
      dermatosparaxis analogous to human Ehlers-Danlos syndrome type VIIC were found to
      be caused by mutations in the procollagen I N-proteinase (pnPI) or ADAMTS2 gene,
      though mutations in other sites are likely responsible for other types of
      dermatosparaxis. Cattle suffering from a form of Marfan syndrome were described
      to have aortic dilatation and aneurysm together with ocular abnormalities and
      skeletal involvement. As in people mutations at different sites of bovine FBN1
      may be responsible for Marfan phenotype. Hereditary equine regional dermal
      asthenia (HERDA), or hyperelastosis cutis, has been recognized in several horse
      breeds as affecting primarily skin, and, occasionally, tendons. A mutation in
      cyclophilin B, a chaperon involved in proper folding of collagens, has been
      identified in some cases. Degenerative suspensory ligament desmitis (DSLD)
      affects primarily tendons and ligaments of certain horse breeds. New data from
      our laboratory showed excessive accumulation of proteoglycans in organs with high
      content of connective tissues. We have identified an abnormal form of decorin
      with altered biological activity in these proteoglycan deposits, and more
      recently changes in processing of aggrecan were found by us and other
      investigators.The naturally occurring diseases of soft tissues in domestic
      animals described here have a potential to serve as good models for analogous
      human diseases. This is the case particularly relevant to dogs as a half out of
      the more than 400 naturally occurring hereditary canine diseases has the
      potential to serve as a model for human disease. 

PMID- 24443031
TI  - Psychosocial aspects of hereditary cancer (PAHC) questionnaire: development and
      testing of a screening questionnaire for use in clinical cancer genetics.
AB  - BACKGROUND: Up to three-quarters of individuals who undergo cancer genetic
      counseling and testing report psychosocial problems specifically related to that
      setting. The objectives of this study were to develop and evaluate the screening
      properties of a questionnaire designed to assess specific psychosocial problems
      related to cancer genetic counseling. METHODS: We adopted the European
      Organisation for Research and Treatment of Cancer Quality of Life Group
      guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC)
      questionnaire, a 26-item questionnaire organized into six problem domains:
      genetics, practical issues, family, living with cancer, emotions, and children.
      The Distress Thermometer and a question per domain on the perceived need for
      extra psychosocial services were included as well. We administered the
      questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at
      the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold
      standard to evaluate the screening properties of the questionnaire, participants
      underwent a semi-structured interview with an experienced social worker who
      assessed the presence and severity of problems per domain. RESULTS: A cutoff
      score representing responses of 'quite a bit' or 'very much' to one or more items
      within a given problem domain yielded moderate to high sensitivity across
      domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The
      questions regarding the perceived need for extra psychosocial services yielded
      high specificity and negative predictive values. CONCLUSION: The Psychosocial
      Aspects of Hereditary Cancer questionnaire in combination with the Distress
      Thermometer can be used as a first-line screener for psychosocial problems within
      the cancer genetic counseling setting.

PMID- 24443032
TI  - Permeability of rapid prototyped artificial bone scaffold structures.
AB  - In this work, various three-dimensional (3D) scaffolds were produced via micro
      stereolithography (u-SLA) and 3D printing (3DP) techniques. This work
      demonstrates the advantages and disadvantages of these two different rapid
      prototyping methods for production of bone scaffolds. Compared to 3DP, SLA
      provides for smaller feature production with better dimensional resolution and
      accuracy. The permeability of these structures was evaluated experimentally and
      via numerical simulation utilizing a newly derived Kozeny-Carman based equation
      for intrinsic permeability. Both experimental and simulation studies took account
      of porosity percentage, pore size, and pore geometry. Porosity content was varied
      from 30% to 70%, pore size from 0.34 mm to 3 mm, and pore geometries of cubic and
      hexagonal closed packed were examined. Two different fluid viscosity levels of 1
      mPa . s and 3.6 mPa . s were used. The experimental and theoretical results
      indicated that permeability increased when larger pore size, increased fluid
      viscosity, and higher percentage porosity were utilized, with highest to lowest
      degree of significance following the same order. Higher viscosity was found to
      result in permeabilities 2.2 to 3.3 times higher than for water. This latter
      result was found to be independent of pore morphology type. As well as
      demonstrating method for determining design parameters most beneficial for
      scaffold structure design, the results also illustrate how the variations in
      patient's blood viscosity can be extremely important in allowing for permeability
      through the bone and scaffold structures.

PMID- 24443034
TI  - Death, treatment decisions and the permanent vegetative state: evidence from
      families and experts.
AB  - Some brain injured patients are left in a permanent vegetative state, i.e., they
      have irreversibly lost their capacity for consciousness but retained some
      autonomic physiological functions, such as breathing unaided. Having discussed
      the controversial nature of the permanent vegetative state as a diagnostic
      category, we turn to the question of the patients' ontological status. Are the
      permanently vegetative alive, dead, or in some other state? We present empirical
      data from interviews with relatives of patients, and with experts, to support the
      view that the ontological state of permanently vegetative patients is unclear:
      such patients are neither straightforwardly alive nor simply dead. Having
      defended this view from counter-arguments we turn to the practical question as to
      how these patients ought to be treated. Some relatives and experts believe it is
      right for patients to be shifted from their currently unclear ontological state
      to that of being straightforwardly dead, but many are concerned or even horrified
      by the only legally sanctioned method guaranteed to achieve this, namely
      withdrawal of clinically assisted nutrition and hydration. A way of addressing
      this distress would be to allow active euthanasia for these patients. This is
      highly controversial; but we argue that standard objections to allowing active
      euthanasia for this particular class of permanently vegetative patients are
      weakened by these patients' distinctive ontological status. 

PMID- 24443033
TI  - Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum
      malaria.
AB  - BACKGROUND: The World Health Organization (WHO) recommends Artemisinin-based
      Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum
      malaria. This review aims to assist the decision-making of malaria control
      programmes by providing an overview of the relative effects of dihydroartemisinin
      piperaquine (DHA-P) versus other recommended ACTs. OBJECTIVES: To evaluate the
      effectiveness and safety of DHA-P compared to other ACTs for treating
      uncomplicated P. falciparum malaria in adults and children. SEARCH METHODS: We
      searched the Cochrane Infectious Diseases Group Specialized Register; the
      Cochrane Central Register of Controlled Trials (CENTRAL) published in The
      Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled
      Trials (mRCT) up to July 2013. SELECTION CRITERIA: Randomized controlled trials
      comparing a three-day course of DHA-P to a three-day course of an alternative WHO
      recommended ACT in uncomplicated P. falciparum malaria. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trials for eligibility and risk of
      bias, and extracted data. We analysed primary outcomes in line with the WHO
      'Protocol for assessing and monitoring antimalarial drug efficacy' and compared
      drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary
      outcomes were effects on gametocytes, haemoglobin, and adverse events. We
      assessed the quality of evidence using the GRADE approach. MAIN RESULTS: We
      included 27 trials, enrolling 16,382 adults and children, and conducted between
      2002 and 2010. Most trials excluded infants aged less than six months and
      pregnant women. DHA-P versus artemether-lumefantrineIn Africa, over 28 days
      follow-up, DHA-P is superior to artemether-lumefantrine at preventing further
      parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39,
      nine trials, 6200 participants, high quality evidence), and although PCR-adjusted
      treatment failure was below 5% for both ACTs, it was consistently lower with DHA
      P (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials,
      5417 participants, high quality evidence). DHA-P has a longer prophylactic effect
      on new infections which may last for up to 63 days (PCR-unadjusted treatment
      failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high
      quality evidence).In Asia and Oceania, no differences have been shown at day 28
      (four trials, 1143 participants, moderate quality evidence), or day 63 (one
      trial, 323 participants, low quality evidence).Compared to artemether
      lumefantrine, no difference was seen in prolonged QTc (low quality evidence), and
      no cardiac arrhythmias were reported. The frequency of other adverse events is
      probably similar with both combinations (moderate quality evidence). DHA-P versus
      artesunate plus mefloquineIn Asia, over 28 days follow-up, DHA-P is as effective
      as artesunate plus mefloquine at preventing further parasitaemia (PCR-unadjusted
      treatment failure: eight trials, 3487 participants, high quality evidence). Once
      adjusted by PCR to exclude new infections, treatment failure at day 28 was below
      5% for both ACTs in all eight trials, but lower with DHA-P in two trials (PCR
      adjusted treatment failure: RR 0.41 95% CI 0.21 to 0.80, eight trials, 3482
      participants, high quality evidence). Both combinations contain partner drugs
      with very long half-lives and no consistent benefit in preventing new infections
      has been seen over 63 days follow-up (PCR-unadjusted treatment failure: five
      trials, 2715 participants, moderate quality evidence).In the only trial from
      South America, there were fewer recurrent parastaemias over 63 days with
      artesunate plus mefloquine (PCR-unadjusted treatment failure: RR 6.19, 95% CI
      1.40 to 27.35, one trial, 445 participants, low quality evidence), but no
      differences were seen once adjusted for new infections (PCR-adjusted treatment
      failure: one trial, 435 participants, low quality evidence).DHA-P is associated
      with less nausea, vomiting, dizziness, sleeplessness, and palpitations compared
      to artesunate plus mefloquine (moderate quality evidence). DHA-P was associated
      with more frequent prolongation of the QTc interval (low quality evidence), but
      no cardiac arrhythmias were reported. AUTHORS' CONCLUSIONS: In Africa,
      dihydroartemisinin-piperaquine reduces overall treatment failure compared to
      artemether-lumefantrine, although both drugs have PCR-adjusted failure rates of
      less than 5%. In Asia, dihydroartemisinin-piperaquine is as effective as
      artesunate plus mefloquine, and is better tolerated.

PMID- 24443035
TI  - Duty-cycled multi-electrode radiofrequency vs. conventional irrigated point-by
      point radiofrequency ablation for recurrent atrial fibrillation: comparative 3
      year data.
AB  - AIMS: Pulmonary vein isolation (PVI) is an accepted treatment to relieve symptoms
      in patients with atrial fibrillation (AF). We studied 3 year outcome after PVI
      guided by duty-cycled multi-electrode radiofrequency (RF) ablation (pulmonary
      vein ablation catheter, PVAC) and provided comparative data to outcome after
      conventional PVI (CPVI) using mapping with irrigated, point-per-point RF
      ablation. METHODS AND RESULTS: One hundred and sixty-one consecutive patients
      with symptomatic paroxysmal or persistent AF and minimal heart disease underwent
      PVI (PVAC, n = 79 vs. CPVI, n = 82). Follow-up (with symptom-guided rhythm
      monitoring) was truncated at 3 years in all patients. Success was defined as
      freedom of documented arrhythmia after a single procedure and without
      antiarrhythmic drug treatment (ADT). Baseline characteristics did not differ
      between both groups. At 3 years follow-up, single-procedure success without ADT
      was comparable between PVAC and CPVI (65% vs. 55%, P = NS). The majority of
      recurrences occurred during the first year (PVAC 79% vs. CPVI 70%, P = NS). The
      annual rate of very late recurrence (i.e. beyond 1 year) was similar in both
      groups (10.5% vs. 15%, P = NS). CONCLUSION: At 3 years follow-up, outcome after
      PVAC-guided PVI is comparable to conventional isolation by irrigated point-by
      point RF ablation. In both strategies, the majority of recurrences occurred in
      the first year of ablation.

PMID- 24443036
TI  - In reference to Regional peak mucosal cooling predicts the perception of nasal
      patency.

PMID- 24443037
TI  - National institute of mental health clinical research career opportunities.
AB  - Mental health professionals interested in clinical research careers need
      accurate, current information about research support mechanisms of the National
      Institute of Mental Health (NIMH). NIMH has recently expanded the research
      opportunities it offers in response to increased interest by the public and by
      Congress in schizophrenia, AIDS, and mental disorders of the elderly and
      children. This article describes the various types of NIMH programs available and
      their goals, criteria, and time and budget limitations. It also summarizes the
      grant review process and the role of NIMH program staff. Descriptions of new and
      revised grant mechanisms, including small grants, FIRST awards, Scientist
      Development Awards, and Academic Awards, and requirements for NIMH extramural and
      intramural fellowships and investigator-initiated training fellowships are also
      outlined. 

PMID- 24443038
TI  - How much psychiatry are medical students really learning? : a reappraisal after
      two decades.
AB  - The results of a survey conducted in 1986 of the attitudes of nonpsychiatric
      house staff toward their psychiatric training in medical school were compared
      with the results of a similar survey conducted in 1966. Compared to the 1966
      cohort, the 1986 cohort reported markedly reduced emphasis on the teaching of
      psychodynamics and an increased emphasis on neurobiology. Psychiatry continued to
      be regarded as the most poorly taught and the least well learned subject in
      medical school. However, a significantly smaller proportion of the later cohort
      than the earlier group felt they had not learned as much psychiatry as they would
      need to practice medicine. Areas of teaching singled out for criticism included
      the quality of instruction and its relevance to patient management. 

PMID- 24443039
TI  - How recent medical school graduates evaluate the clinical relevancy of their
      behavioral science curriculum.
AB  - Recent graduates of the University of South Carolina School of Medicine (n=108)
      evaluated the clinical relevancy of their behavioral science curriculum. The
      results indicate that a body of behavioral science data are clinically relevant
      to physicians regardless of their specialty. Additional behavioral science
      content areas are clinically relevant for practitioners in particular medical
      specialties. Suggestions are made for the role of behavioral science material in
      continuing medical education. 

PMID- 24443040
TI  - Patients' satisfaction with care received in teaching settings.
AB  - Voluntary psychiatric patients (N=118) on a teaching ward were asked to identify
      their medical personnel and rate their satisfaction with the care they received.
      The patients were proficient in distinguishing between psychiatrists, psychiatric
      residents, and medical students and were highly satisfied with the care they
      received. Patients over 35 were better at identifying residents than younger
      patients and also rated the quality of care pro-vided by psychiatrists more
      highly. Patients with adjustment reaction with depressed mood rated the quality
      of care provided by psychiatrists lower than did patients with major depression,
      bipolar affective disorder, or psychosis. Female patients rated their
      psychiatrists more highly than did male patients. 

PMID- 24443041
TI  - Group psychotherapy in psychiatric residency training.
AB  - Residents (n=114) in the department of psychiatry at the University of Toronto
      were surveyed in the spring of 1987 about their training in and attitudes about
      group psychotherapy. Significant interest in group psychotherapy was correlated
      positively with a perception that one's group psychotherapy training was good,
      more hours of experience leading groups, a belief in the usefulness of group
      therapy in one's future practice, and an appreciation of opportunities to refer
      patients to group therapy. Confidence in one's ability as a group leader and
      knowledge about group therapy were correlated with the number of hours spent
      leading groups. The implications for planners of group psychotherapy training
      curricula and faculty are discussed and recommendations are made concerning the
      principles of group psychotherapy training programs. 

PMID- 24443042
TI  - The role of religion in psychiatric education: a national survey.
AB  - Approximately 80% of the members of the American Association of Directors of
      Psychiatric Residency Training responded to a survey on the role of religion in
      psychiatric education. Survey results suggest that religious ideation by resident
      candidates is a relatively unimportant variable in the programs' selection;
      didactic instruction on any aspect of religion is infrequent; clinical
      supervision on religious dynamics is variable but more likely to occur than
      didactic instruction; and academic progression is rarely impeded by behaviors
      emanating from residents' religious values. Several implications of these
      findings are discussed. 

PMID- 24443043
TI  - Starting fights: the debate as teaching tool.
AB  - During a one-year experiment in postgraduate psychiatric education, residents
      participated in live debates instead of attending traditional lectures and
      seminars. A variety of controversial topics in psychiatry were covered. Both
      residents and faculty rated the debate as a thought-provoking and highly
      effective teaching tool, and a fun one, to boot. 

PMID- 24443044
TI  - The many quests of psychiatrists: how well can we fulfill them?

PMID- 24443045
TI  - A Fuller History of the PRITE.

PMID- 24443046
TI  - In reply.

PMID- 24443047
TI  - Sorption-desorption and transport of trimethoprim and sulfonamide antibiotics in
      agricultural soil: effect of soil type, dissolved organic matter, and pH.
AB  - Use of animal manure is a main source of veterinary pharmaceuticals (VPs) in soil
      and groundwater through a series of migration processes. The sorption-desorption
      and transport of four commonly used VPs including trimethoprim (TMP),
      sulfapyridine, sulfameter, and sulfadimethoxine were investigated in three soil
      layers taken from an agricultural field in Chongming Island China and two types
      of aqueous solution (0.01 M CaCl2 solution and wastewater treatment plant
      effluent). Results from sorption-desorption experiments showed that the sorption
      behavior of selected VPs conformed to the Freundlich isotherm equation. TMP
      exhibited higher distribution coefficients (K d = 6.73-9.21) than other
      sulfonamides (K d = 0.03-0.47), indicating a much stronger adsorption capacity of
      TMP. The percentage of desorption for TMP in a range of 8-12 % is not so high to
      be considered significant. Low pH (<pK a of tested VPs) and rich soil organic
      matter (e.g., 0-20 cm soil sample) had a positive impact on sorption of VPs.
      Slightly lower distribution coefficients were obtained for VPs in wastewater
      treatment plant (WWTP) effluent, which suggested that dissolved organic matter
      might affect their sorption behavior. Column studies indicated that the transport
      of VPs in the soil column was mainly influenced by sorption capacity. The weakly
      adsorbed sulfonamides had a high recovery rate (63.6-98.0 %) in the leachate,
      while the recovery rate of TMP was only 4.2-10.4 %. The sulfonamides and TMP
      exhibited stronger retaining capacity in 20-80 cm and 0-20 cm soil samples,
      respectively. The transport of VPs was slightly higher in the columns leached by
      WWTP effluent than by CaCl2 solution (0.01 M) due to their sorption interactions.

PMID- 24443048
TI  - Monitoring of PCDD/Fs and dioxin-like PCBs and seasonal variations in mussels
      from the Mar Grande and the Mar Piccolo of Taranto (Ionian Sea, Southern Italy).
AB  - The levels and specific profiles of polychlorinated dibenzo-p-dioxins,
      dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in
      Mytilus galloprovincialis from the Mar Grande and the Mar Piccolo of Taranto were
      determined during the extensive monitoring plan of Local Health Authority to
      assess PCDD/Fs and DL-PCBs contamination in food and farm products, within 20 km
      from the industrial areas of Taranto, between March and December 2011. The
      average Total Toxicity Equivalence (TEQ) values for the sum of PCDD/F and DL-PCBs
      ranged from 1.61 to 5.63 pg WHO2005-TEQ g(-1) wet weight basis, with the highest
      in the first inlet of the Mar Piccolo. In particular, DL-PCBs were the dominant
      chemicals in all samples, followed by PCDFs and PCDDs. Congener patterns in
      mussels were similar, indicating a homogeneous behavior in studied areas and,
      probably, the same type of source. The seasonal concentrations trend showed a
      relevant increase of dioxin and dioxin-like PCBs TEQs during the summer months,
      exceeding the limits set by the European Community for food and foodstuff.
      Reducing PCDD/Fs and PCBs is necessary to decrease contamination levels in order
      to safeguard marine ecosystem and human health in the Taranto area.

PMID- 24443049
TI  - Sensitive time-resolved fluoroimmunoassay for quantitative determination of
      clothianidin in agricultural samples.
AB  - Europium (Eu(3+))-labeled antibody was used as a fluorescent label to develop a
      highly sensitive time-resolved fluoroimmunoassay (TRFIA) for determination of
      clothianidin residues in agricultural samples. Toward this goal, the Eu(3+)
      labeled polyclonal antibody and goat anti-rabbit antibody were prepared for
      developing and evaluating direct competitive TRFIA (dc-TRFIA) and indirect
      competitive TRFIA (ic-TRFIA). Under optimal conditions, the half-maximal
      inhibition concentration (IC50) and the limit of detection (LOD, IC10) of
      clothianidin were 9.20 and 0.0909 MUg/L for the dc-TRFIA and 2.07 and 0.0220
      MUg/L for the ic-TRFIA, respectively. The ic-TRFIA has no obvious cross
      reactivity with the analogues of clothianidin except for dinotefuran. The average
      recoveries of clothianidin from spiked water, soil, cabbage, and rice samples
      were estimated to range from 74.1 to 115.9 %, with relative standard deviations
      of 3.3 to 11.7 %. The results of TRFIA for the blind samples were largely
      consistent with gas chromatography (R (2) = 0.9902). The optimized ic-TRFIA might
      become a sensitive and satisfactory analytical method for the quantitative
      monitoring of clothianidin residues in agricultural samples. 

PMID- 24443050
TI  - Industrial metabolism of chlorine: a case study of a chlor-alkali industrial
      chain.
AB  - Substance flow analysis (SFA) is applied to a case study of chlorine metabolism
      in a chlor-alkali industrial chain. A chain-level SFA model is constructed, and
      eight indices are proposed to analyze and evaluate the metabolic status of
      elemental chlorine. The primary objectives of this study are to identify low
      efficiency links in production processes and to find ways to improve the
      operational performance of the industrial chain. Five-year in-depth data
      collection and analysis revealed that system production efficiency and source
      efficiency continued increasing since 2008, i.e., when the chain was first
      formed, at average annual growth rates of 21.01 % and 1.01 %, respectively. In
      2011, 64.15 % of the total chlorine input was transformed into final products.
      That is, as high as 98.50 % of the chlorine inputs were utilized when other by
      products were counted. Chlorine loss occurred mostly in the form of chloride ions
      in wastewater, and the system loss rate was 0.54 %. The metabolic efficiency of
      chlorine in this case was high, and the chain system had minimal impact on the
      environment. However, from the perspectives of processing depth and economic
      output, the case study of a chlor-alkali industrial chain still requires
      expansion. 

PMID- 24443051
TI  - Effectiveness of rodenticides for managing invasive roof rats and native deer
      mice in orchards.
AB  - Roof rats (Rattus rattus) and deer mice (Peromyscus maniculatus) are occasional
      pests of nut and tree fruit orchards throughout California and in many other
      parts of the USA and beyond. In general, the most practical and cost-effective
      control method for rodents in many agricultural environments is the use of
      rodenticides (toxic baits), but little or no information exists on the efficacy
      of current rodenticides in controlling roof rats and deer mice in orchards.
      Therefore, our goals were to develop an index of rodent activity to monitor
      efficacy of rodenticides and to subsequently test the efficacy of three
      California Department of Food and Agriculture rodenticide baits (0.005 %
      chlorophacinone treated oats, 0.005 % diphacinone treated oats, and 0.005 %
      diphacinone wax block) to determine their utility for controlling roof rats and
      deer mice in agricultural orchards. We determined that a general index using the
      number of roof rat photos taken at a minimum of a 5-min interval was strongly
      correlated to the minimum number known estimate of roof rats; this approach was
      used to monitor roof rat and deer mouse populations pre- and post-treatment. Of
      the baits tested, the 0.005 % diphacinone treated oats was most effective for
      both species; 0.005 % chlorophacinone grain was completely ineffective against
      roof rats. Our use of elevated bait stations proved effective at providing bait
      to target species and should substantially limit access to rodenticides by many
      non-target species. 

PMID- 24443052
TI  - Characteristics, sources, and transport of tetrabromobisphenol A and bisphenol A
      in soils from a typical e-waste recycling area in South China.
AB  - We studied the tetrabromobisphenol A (TBBPA) and bisphenol A (BPA) patterns and
      their sources and transport in different land-use soils from Longtang, South
      China, a typical electronic waste recycling center. We also studied the reductive
      debromination of TBBPA in paddy soils. TBBPA and BPA concentrations (on a dry
      weight basis) were undetected-220 and 0.50-325 ng/g, respectively, and both
      increased, by similar factors, in the following order: pond sediments < paddy
      soils = vegetable soils < wasteland < dismantling sites < former open burning
      sites. BPA concentrations were higher than TBBPA concentrations in all six land
      use soils, and they correlated significantly. TBBPA and BPA were transported
      through the soil profiles, being found at relatively high concentrations in soil
      0-40 cm deep, but only at low concentrations in soil 40-80 cm deep. The surface
      soil concentrations appear to have been strongly affected by crude recycling
      activities, and former open burning and dismantling sites were the main point
      sources. The areas surrounding the open burning sites and dismantling sites have
      been contaminated not only by the dumping of waste residues but also by fly ash
      deposition, even though the agricultural soils are far from the point pollution
      sources. Some BPA in the soils is likely to be the reductive debromination
      product of TBBPA because the long rainy season promotes TBBPA transformation and
      because BPA can persist for a long time. Incubation experiments confirmed that
      TBBPA could be transformed into BPA and that BPA could accumulate in waterlogged
      paddy soils, and this may be why BPA concentrations were higher than TBBPA
      concentrations in the Longtang area. 

PMID- 24443053
TI  - Anatomical brain imaging at 7T using two-dimensional GRASE.
AB  - PURPOSE: Specific absorption rate is a serious problem at high field strengths,
      especially for sequences involving many high power radiofrequency pulses, such as
      turbo spin echo (TSE). GRASE (gradient and spin echo) may overcome this problem
      by omitting a certain number of refocusing pulses of a TSE sequence, and
      replacing them with segmented echo-planar imaging readouts. METHODS: GRASE and
      TSE were compared using similar sequence parameters at a field strength of 7T.
      The signal-to-noise ratio (SNR) per unit time, contrast, and point spread
      function (PSF) were determined. High-resolution human brain images were acquired
      and the implementation of an inversion recovery preparation for T(1) weighting
      was evaluated. RESULTS: TSE and GRASE images at 7T showed very similar SNR and
      contrast. The slightly worse PSF for GRASE is balanced by a significant reduction
      in scan time or increase in spatial coverage compared with TSE. Furthermore,
      implementing an additional inversion recovery preparation enables the acquisition
      of T(1)-weighted images with high SNR per unit time. CONCLUSION: GRASE is highly
      suitable for structural scanning at ultra-high field strengths and is a valid
      alternative to the commonly used TSE sequence.

PMID- 24443054
TI  - Laboratory validation of a new gas-enhanced dentine liquid permeation evaluation
      system.
AB  - AIM: To validate a new automated dentine permeability testing platform based on
      pressure change measurements. METHODOLOGY: A split chamber was designed allowing
      for concomitant measurement of fluid permeation and pressure difference. In a
      first test, system reliability was assessed by interposing a solid metal disk,
      embedded composite resin disks, or teeth by consecutively measuring eight times
      under standardized conditions. Secondly, the repeatability and applicability of
      the method was tested in a dentine wound model by using intact third molars:
      Class I (2 * 5 mm) and a full occlusal preparation as well a ceramic restoration
      were consecutively performed and repeatedly measured eight times each. In the
      last test, the system detection limit as well correlation between gas pressure
      difference and liquid permeation were evaluated: Again, third molars were used
      and occlusal preparations of increasing size (2 * 5, 3 * 5, 4 * 5, and 5 * 5 mm
      and full occlusal preparations, respectively) were made. Data was analyzed for
      the linearity of measurement, and R (2) values were calculated. RESULTS: The
      embedding procedure allowed for perfect separation of the two chambers, and no
      significant variation in repeated measurements of evaluated samples for the
      respective treatments (p = 0.05) was found. The detection was 0.002 hPa/min for
      the pressure slope and 0.0225 MUl/min for the fluid infiltration, respectively.
      The saline volume was highly correlating to the gas pressure changes (R (2) =
      0.996, p < 0.0001). CONCLUSIONS: The presented method is a reliable and exact
      tool to assess dentine permeability by nondestructive and repeatable
      measurements. CLINICAL RELEVANCE: This method is suitable for measurements and
      comparison of the effectiveness of dentine wounds sealing materials.

PMID- 24443055
TI  - An expanded population of CD34+ cells from frozen banked umbilical cord blood
      demonstrate tissue repair mechanisms of mesenchymal stromal cells and circulating
      angiogenic cells in an ischemic hind limb model.
AB  - Peripheral vascular disease affects ~20 % of the population over 50 years of age
      and is a complication of type 2 diabetes. Cell therapy studies revealed that
      cells from older or diabetic donors have a reduced capacity to induce tissue
      repair compared to healthy and younger cells. This fact greatly impedes the use
      of autologous cells for treatment. Umbilical cord blood CD34+ cells are a source
      of angiogenic cells but unlike bone marrow CD34+ angiogenic cells, achieving
      clinically significant cell numbers has been difficult without in vitro
      expansion. We report here that culturing CD34+/CD45+ blood cells from frozen
      umbilical cord blood units in a medium supplemented with FGF4, SCF and FLT3
      ligand produced a population of cells that remain CD34+/CD45+ but have an
      increased capacity for tissue healing. The cultured CD34+ cells were compared
      directly to non-cultured CD34+ cells in a mouse model of ischemia. Cultured CD34+
      cells demonstrated strong paracrine signaling as well as the capacity to
      differentiate into endothelial cells, smooth muscle and striated muscle. We
      observed an improvement in blood flow and a significant reduction in foot
      necrosis. A second study was completed to assess the safety of the cells. No
      adverse effects were associated with the injection of the cultured cells. Our
      method described here for culturing umbilical cord blood cells resulted in cells
      with a strong paracrine effect that induces substantial tissue repair in a murine
      model of hind limb ischemia and evidence of engraftment and differentiation of
      the cultured cells into new vasculature and muscle. 

PMID- 24443056
TI  - Sulfonylurea receptor 1 contributes to the astrocyte swelling and brain edema in
      acute liver failure.
AB  - Astrocyte swelling (cytotoxic brain edema) is the major neurological complication
      of acute liver failure (ALF), a condition in which ammonia has been strongly
      implicated in its etiology. Ion channels and transporters are known to be
      involved in cell volume regulation, and a disturbance in these systems may result
      in cell swelling. One ion channel known to contribute to astrocyte swelling/brain
      edema in other neurological disorders is the ATP-dependent, nonselective cation
      (NCCa-ATP) channel. We therefore examined its potential role in the astrocyte
      swelling/brain edema associated with ALF. Cultured astrocytes treated with 5 mM
      ammonia showed a threefold increase in the sulfonylurea receptor type 1 (SUR1)
      protein expression, a marker of NCCa-ATP channel activity. Blocking SUR1 with
      glibenclamide significantly reduced the ammonia-induced cell swelling in cultured
      astrocytes. Additionally, overexpression of SUR1 in ammonia-treated cultured
      astrocytes was significantly reduced by cotreatment of cells with BAY 11-7082, an
      inhibitor of NF-kappaB, indicating the involvement of an NF-kappaB-mediated SUR1
      upregulation in the mechanism of ammonia-induced astrocyte swelling. Brain SUR1
      mRNA level was also found to be increased in the thioacetamide (TAA) rat model of
      ALF. Additionally, we found a significant increase in SUR1 protein expression in
      rat brain cortical astrocytes in TAA-treated rats. Treatment with glibenclamide
      significantly reduced the brain edema in this model of ALF. These findings
      strongly suggest the involvement of NCCa-ATP channel in the astrocyte
      swelling/brain edema in ALF and that targeting this channel may represent a
      useful approach for the treatment of the brain edema associated with ALF.

PMID- 24443057
TI  - 25th anniversary article: organic field-effect transistors: the path beyond
      amorphous silicon.
AB  - Over the past 25 years, organic field-effect transistors (OFETs) have witnessed
      impressive improvements in materials performance by 3-4 orders of magnitude, and
      many of the key materials discoveries have been published in Advanced Materials.
      This includes some of the most recent demonstrations of organic field-effect
      transistors with performance that clearly exceeds that of benchmark amorphous
      silicon-based devices. In this article, state-of-the-art in OFETs are reviewed in
      light of requirements for demanding future applications, in particular active
      matrix addressing for flexible organic light-emitting diode (OLED) displays. An
      overview is provided over both small molecule and conjugated polymer materials
      for which field-effect mobilities exceeding > 1 cm(2) V(-1) s(-1) have been
      reported. Current understanding is also reviewed of their charge transport
      physics that allows reaching such unexpectedly high mobilities in these weakly
      van der Waals bonded and structurally comparatively disordered materials with a
      view towards understanding the potential for further improvement in performance
      in the future. 

PMID- 24443060
TI  - Editorial--Is there still a place for breath tests in gastroenterology?

PMID- 24443058
TI  - TAK1 regulates hepatic cell survival and carcinogenesis.
AB  - TGF-beta-activated kinase 1 (TAK1 or MAP3K7) is an intracellular hub molecule
      that regulates both nuclear factor-kappaB (NF-kappaB) and mitogen-activated
      protein kinase (MAPK) signaling pathways that play key roles in development, cell
      survival, immune response, metabolism, and carcinogenesis. TAK1 activity is
      tightly regulated by its binding proteins, TAB1 and TAB2/TAB3, as well as by post
      translational modification including ubiquitination and phosphorylation.
      Accumulating evidence demonstrates that TAK1 plays a role in tumor initiation,
      progression, and metastasis as a tumor prompter or tumor suppressor. An
      understanding of the role of TAK1 in liver physiology and diseases is required
      for the development of therapeutic agencies targeting TAK1. In this review, we
      highlight the activation mechanism and pathophysiological roles of TAK1 in the
      liver. 

PMID- 24443061
TI  - Intestinal gas production and gastrointestinal symptoms: from pathogenesis to
      clinical implication.
AB  - Intestinal gases are the expression of metabolic activity of gut microbiota in
      the gut, particularly carbohydrates in the case of H2, CH4. Alterations in
      composition of gases and air handling, directly or upon challenge with food are
      relevant for GI and extra-GI diseases. Assessing gas composition in breath can be
      a very useful tool for clinic, but technical issues are crucial (breath sampling,
      storing and analyzing). Aim of the present review is to summarize the
      understanding of the importance of intestinal gases in gastro-intestinal
      physiology and patho-physiology. Practical considerations on how to collect
      samples and instruments available for the clinic have also been provided. 

PMID- 24443062
TI  - The role of gut microbiota in the pathogenesis and management of allergic
      diseases.
AB  - Allergy is defined as a hypersensitivity reaction due to specific antibody
      mediated or cell-mediated immunologic mechanisms. Epidemiological studies are
      showing a dramatic increase of allergies in industrialized countries in the last
      few decades, while remaining stable in developing countries. In 1989 Strachan,
      hypothesized that the increase in allergic disorders was the result of a lack of
      infections in early infancy, and in 1998 Wold suggested that, rather than a
      decrease in viral or bacterial infections, an altered normal intestinal
      colonization pattern in infancy, could be responsible for the increase in
      allergies. Germ-free mice were shown to mount an exaggerated allergic airway
      reaction compared with that seen in colonized mice, indicating the important role
      of microbe-host interactions in the development of allergic diseases. Infants
      with food allergies are found to exhibit an imbalance between "beneficial"and
      potentially harmful bacteria, i.e., decreased Lactobacilli, Bifidobacteria and
      Enterococcus species and increased coliforms, Staphylococcus aureus and
      Clostridium species, suggesting that microbial inhabitants of the human body, may
      play either a pathogenic or protective role in allergies. Based on this data,
      many clinical trial addressing the use of probiotics in the context of allergic
      disorders, have been conducted in children. However, currently, no conclusive
      item may be drawn. 

PMID- 24443059
TI  - Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer.
AB  - Obesity and associated metabolic disorders have been implicated in liver
      carcinogenesis; however, there are little data on the role of obesity-related
      biomarkers on liver cancer risk. We studied prospectively the association of
      inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma
      (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers
      outside of the liver (GBTC) in a nested case-control study within the European
      Prospective Investigation into Cancer and Nutrition. Over an average of 7.7
      years, 296 participants developed HCC (n=125), GBTC (n=137), or IBD (n=34). Using
      risk-set sampling, controls were selected in a 2:1 ratio and matched for
      recruitment center, age, sex, fasting status, and time of blood collection.
      Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6),
      C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and
      glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and
      95% confidence intervals (CIs) were estimated using conditional logistic
      regression. After adjustment for lifestyle factors, diabetes, hepatitis
      infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide,
      and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling
      of concentrations=1.22; 95% CI=1.02-1.46; P=0.03; 1.90; 95% CI=1.30-2.77;
      P=0.001; 2.25; 95% CI=1.43-3.54; P=0.0005; and 2.09; 95% CI=1.19-3.67; P=0.01,
      respectively). CRP was associated also with risk of GBTC (IRR=1.22; 95% CI=1.05
      1.42; P=0.01). GLDH was associated with risks of HCC (IRR=1.62; 95% CI=1.25-2.11;
      P=0.0003) and IBD (IRR=10.5; 95% CI=2.20-50.90; P=0.003). The continuous net
      reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin
      and 0.46 for GLDH, indicating good predictive ability of these biomarkers.
      CONCLUSION: Elevated levels of biomarkers of inflammation and hyperinsulinemia
      are associated with a higher risk of HCC, independent of obesity and established
      liver cancer risk factors.

PMID- 24443063
TI  - Lactose intolerance: from diagnosis to correct management.
AB  - This review discusses one of the most relevant problems in gastrointestinal
      clinical practice: lactose intolerance. The role of lactase-persistence alleles
      the diagnosis of lactose malabsorption the development of lactose intolerance
      symptoms and its management. Most people are born with the ability to digest
      lactose, the major carbohydrate in milk and the main source of nutrition until
      weaning. Approximately, 75% of the world's population loses this ability at some
      point, while others can digest lactose into adulthood. Symptoms of lactose
      intolerance include abdominal pain, bloating, flatulence and diarrhea with a
      considerable intraindividual and interindividual variability in the severity.
      Diagnosis is most commonly performed by the non invasive lactose hydrogen breath
      test. Management of lactose intolerance consists of two possible clinical choice
      not mutually exclusive: alimentary restriction and drug therapy.

PMID- 24443064
TI  - Fructose, trehalose and sorbitol malabsorption.
AB  - Carbohydrate malabsorption is a frequent clinical condition, often associated
      with abdominal symptoms. Although lactose represents the most commonly
      malabsorbed sugar, also other carbohydrates, such as fructose, trehalose and
      sorbitol may be incorrectly absorbed in the small intestine. Fructose
      malabsorption seems more common in patients with functional bowel disease, even
      if randomized and controlled studies on these topic were few and on small
      samples. Interpretation of breath hydrogen testing is difficult. In particular,
      neither studies comparing this test with a gold standard, nor validated doses and
      concentrations to be used, are available. Trehalose malabsorption due to
      trehalase deficiency represents a very rare condition and available studies do
      not support its relevance in clinical practice. Sorbitol absorption is dose and
      concentration related, and depends on the entity of intestinal absorption
      surface. Nevertheless, the finding of its malabsorption is not expression of a
      specific cause of intestinal bowel damage. From available data, it is not
      possible to draw definite conclusions about clinical relevance of fructose,
      trehalose and sorbitol malabsorption, as well as, about diagnostic accuracy of
      commonly used tests to detect all these conditions. On the other hand, in
      patients who refer abdominal discomfort after ingestion of different carbohydrate
      containing foods, a small intestinal bacterial overgrowth, should be promptly
      considered. This is because the large amount of intestinal bacteria may
      unspecifically ferment sugars, causing an abnormal H2 production and consequently
      a misleading diagnosis of sugar malabsorption.

PMID- 24443065
TI  - Diagnosis of small intestinal bacterial overgrowth in the clinical practice.
AB  - BACKGROUND: Gut microbiota plays several beneficial effects on the human host.
      Its qualitative and/or quantitative unbalance may facilitate the occurrence of
      small intestinal bacterial overgrowth (SIBO). AIM: To review the available data
      in order to propose a practical approach to SIBO diagnosis in the clinical
      setting. MATERIALS AND METHODS: Full papers from 1990 to present available on the
      Pubmed database concerning the topic of SIBO diagnosis were critically reviewed.
      RESULTS: SIBO is common in the presence of one or more predisposing conditions.
      The clinical picture of SIBO patients is extremely variable, depending of
      underlying disorders, and both patients and microbiota characteristics. SIBO
      could be asymptomatic, or leading to aspecific gastrointestinal IBS-like
      symptoms. In worst cases it may configure a real malabsorption syndrome. Culture
      of intestinal aspirates remains at present the gold standard for SIBO diagnosis.
      However a lot of limitations including high costs and invasivity prevent from
      using this test in the clinical practice. Hydrogen lactulose and especially
      glucose breath tests are at present the most utilized to reach SIBO diagnosis in
      the clinical setting, due to their low costs, non invasivity, sufficient accuracy
      and reproducibility. CONCLUSIONS: SIBO should be suspected in the presence of IBS
      like symptoms and/or malabsorption syndrome occurring in the presence of
      disorders predisposing to SIBO development. The most common diagnostic tool is
      represented at present by hydrogen breath tests.

PMID- 24443066
TI  - Hydrogen breath test and intestinal gas production.
AB  - Despite extensive use in clinical practice, difficulties regarding interpretation
      of hydrogen breath test are still very frequent, even on research grounds. After
      the administration of a non-absorbable sugar, such as lactulose, an increase of
      breath hydrogen and methane is evident; this phenomenon is considered an index of
      colonic fermentation. It is not clear, however, if the levels of these compounds
      correlate with the presence and severity of functional symptoms, nor if they
      accurately reflect gas production at colonic level. So far, apart from
      flatulence, we have no indications regarding the ability of hydrogen or methane
      to act as biomarkers of intraluminal events. On the other hand, it has been shown
      that in functional bowel disease a colonic dysbiosis exists, and that the
      modification of bacterial flora might result in a reduction of symptom severity.
      Consequently, it is not clear if hydrogen and methane colonic production could
      have a role in the pathophysiology of functional complaints, but it is possible
      that other fermentation products should be taken into consideration, such as
      acetate, propionate, and alcohol. 

PMID- 24443067
TI  - Breath tests for the assessment of the orocecal transit time.
AB  - Orocecal transit time (OCTT) is one of the main determinant of the hunger ratings
      and gastrointestinal sensitivity. While marked-isotopes scintigraphy is the gold
      standard in its determination in the clinical frame, breath tests are cheap, well
      tolerated and non-invasive alternatives. In fact C-13 and C-14 stable isotopes
      breath tests can be used to assess gastric emptying and OCTT in the clinical and
      research frames. Moreover, hydrogen (H2) lactulose breath test can be used to
      assess OCTT in the research frame only due to its laxative action; inulin breath
      test, devoid of this bias, could be replacing it. However, the main limitation in
      the use of breath tests in the OCTT determination is their low reproducibility. 

PMID- 24443068
TI  - Specific 13C functional pathways as diagnostic targets in gastroenterology breath
      tests: tricks for a correct interpretation.
AB  - Breath tests are non-invasive, non-radioactive, safe, simple and effective tests
      able to determine significant metabolic alterations due to specific diseases or
      lack of specific enzymes. Carbon isotope (13)C, the stable-non radioactive
      isotope of carbon, is the most used substrate in breath testing, in which
      (13)C/(12)C ratio is measured and expressed as a delta value, a differences
      between readings and a fixed standard. (13)C/(12)C ratio is measured with isotope
      ratio mass spectrometry or non-dispersive isotope-selective infrared spectrometer
      and generally there is a good agreement between these techniques in the isotope
      ratio estimation. (13)C/(12)C ratio can be expressed as static measurement (like
      delta over baseline in urea breath test) or as dynamic measurement as percent
      dose recovery, but more dosages are necessary. (13)C Breath-tests are involved in
      many fields of interest within gastroenterology, such as detection of
      Helicobacter pylori infection, study of gastric emptying, assessment of liver and
      exocrine pancreatic functions, determination of oro-caecal transit time,
      evaluation of absorption and to a lesser extend detection of bacterial
      overgrowth. The use of every single test in a clinical setting is vary depending
      on accuracy and substrate costs. This review is meant to present (13)C the
      meaning of (13)C/(12)C ratio and static and dynamic measure and, finally, the
      instruments dedicated to its use in gastroenterology. A brief presentation of
      (13)C breath tests in gastroenterology is also provided.

PMID- 24443069
TI  - 13C-Urea breath test for the diagnosis of Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) is a Gram-negative bacterium able to colonize the
      gastric mucosa as well as gastric metaplastic areas of the duodenum, producing
      inflammation. The clinical outcome depends on sophisticated interactions between
      bacterial factors, such as the expression of determinants of virulence and
      pathogenicity, and host characteristics. The severity of inflammation, may then
      vary among different subjects, leading to the occurrence of different
      gastroduodenal diseases, ranging from chronic gastritis to gastric cancer and
      MALT-lymphoma, to some defined extragastric manifestations. Many diagnostic tests
      are available for the detection of H. pylori infection including noninvasive
      methods, such as serology, (13)C-urea breath test (UBT), and fecal antigen tests
      and invasive techniques, including a combined use of endoscopic biopsy-based
      methods, such as rapid urease testing, histology, culture, and molecular methods.
      UBT is a highly sensitive and specific and allows to diagnose the presence or
      absence of infection of H. pylori, through the oral administration of a solution
      containing urea labelled with the non-radioactive natural carbon 13. This review
      article analyzes microbiological and clinical features of H. pylori as well as
      the different diagnostic tests able to detect this bacterium with a special focus
      on UBT.

PMID- 24443070
TI  - 13C-octanoic acid breath test to study gastric emptying time.
AB  - Digestion is a complex process regulated by several factors. Among these, one of
      the most important is the time of gastric emptying. A delayed gastric emptying
      time can be caused by several factors and can generate considerable discomfort in
      humans. It ranges from mild to real debilitating disorders. Until now, different
      tests are suggested to study the gastric emptying time. The present review
      presents the mayor cause and the main symptoms linked to delayed gastric emptying
      and will focus on the (13)C-octanoid acid breath test, as a good candidate for
      studying solid gastric emptying time.

PMID- 24443071
TI  - Pancreatic function assessment.
AB  - Several non invasive tests are available to assess pancreatic function, but no
      one is routinely used in clinical practice to diagnose chronic pancreatitis, due
      to their poor sensitivity in diagnosing mild pancreatic insufficiency. (13)C
      breath tests share the same limits of the other non invasive functional tests,
      but the mixed triglyceride breath test seems to be useful in finding the correct
      dosage of enzyme substitutive therapy to prevent malnutrition in patients with
      known pancreatic insufficiency.

PMID- 24443072
TI  - Breath tests with novel 13C-substrates for clinical studies of liver
      mitochondrial function in health and disease.
AB  - Mitochondrial dysfunction determines the onset and progression of chronic
      deleterious conditions including liver diseases. The in vivo assessment of
      mitochondrial function, by providing more insight into the pathogenesis of liver
      diseases, would be a helpful tool to study specific functions and to develop
      diagnostic, prognostic and therapeutic strategies. The application of breath
      tests in the clinical setting to evaluate mitochondrial fitness may elegantly and
      noninvasively overcome the difficulties due to previous complex techniques and
      may provide clinically relevant information, i.e the effects of drugs presenting
      mitochondrial liabilities. Substrates meeting this requirement include alpha
      ketoisocaproic acid and methionine, both decarboxylated by mitochondria. Long and
      medium chain fatty acids that are metabolized through the Krebs cycle and benzoic
      acid, which undergoes glycine conjugation, may also reflect the mitochondrial
      performance. This review focuses on the utility of breath tests to assess
      mitochondrial function in humans, thus contributing to unravel potential
      mechanisms associated with the dysfunction of this organelle network in the
      pathophysiology of liver diseases. 

PMID- 24443073
TI  - Potential use of liver function breath tests in the clinical practice.
AB  - BACKGROUND: Assessment of hepatic functional reserve in acute and chronic liver
      disease is a discriminating factor for prognostic and therapeutic reasons. For
      this reason dynamic liver function tests have been developed. AIM: To review the
      breath method with stable carbon isotopes in hepatological setting. MATERIALS AND
      METHODS: We conducted a literature review to analyze the experimental evidence
      about the diagnostic potential of breath tests of liver function. RESULTS: Liver
      breath tests are able to discriminate between healthy subjects and patients with
      liver cirrhosis. The use for the assessment of liver fibrosis seems to be still
      burdened with less capability to discriminate between intermediate stages.
      CONCLUSIONS: Liver breath test are a promising tool for the evaluation of hepatic
      functional reserve but the use of such methods in clinical practice is limited to
      specialized or research centers. Most extensive studies are necessary to
      facilitate the spread of these methods in clinical practice.

PMID- 24443074
TI  - Tricks for interpreting and making a good report on hydrogen and 13C breath
      tests.
AB  - Breath tests (BT) represent a valid and non-invasive diagnostic tool in many
      gastroenterological disorders. Their wide diffusion is due to the low cost,
      simplicity and reproducibility and their common indications include diagnosis of
      carbohydrate malabsorption, Helicobacter pylori infection, small bowel bacterial
      overgrowth, gastric emptying time and orocaecal transit time. The review deals
      with key points on methodology, which would influence the correct interpretation
      of the test and on a correct report. While a clear guideline is available for
      lactose and glucose breath tests, no gold standard is available for Sorbitol,
      Fructose or other H2 BTs. Orocaecal transit time (OCTT) defined as time between
      assumption of 10 g lactulose and a peak > 10 ppm over the baseline value, is a
      well-defined breath test. The possible value of lactulose as a diagnostic test
      for the diagnosis of small bowel bacterial overgrowth is still under debate.
      Among (13)C breath test, the best and well characterized is represented by the
      urea breath test. Well-defined protocols are available also for other (13)C
      tests, although a reimbursement for these tests is still not available. Critical
      points in breath testing include the patient preparation for test, type of
      substrate utilized, reading machines, time between when the test is performed and
      when the test is processed. Another crucial point involves clinical conclusions
      coming from each test. For example, even if lactulose could be utilized for
      diagnosing small bowel bacterial overgrowth, this indication should be only
      secondary to orocaecal transit time, and added into notes, as clinical guidelines
      are still uncertain.

PMID- 24443075
TI  - Breath tests sustainability in hospital settings: cost analysis and reimbursement
      in the Italian National Health System.
AB  - The high demand of Breath Tests (BT) in many gastroenterological conditions in
      time of limited resources for health care systems, generates increased interest
      in cost analysis from the point of view of the delivery of services to better
      understand how use the money to generate value. This study aims to measure the
      cost of C13 Urea and other most utilized breath tests in order to describe key
      aspects of costs and reimbursements looking at the economic sustainability for
      the hospital. A hospital based cost-analysis of the main breath tests commonly
      delivery in an ambulatory setting is performed. Mean salary for professional
      nurses and gastroenterologists, drugs/preparation used and disposable materials,
      purchase and depreciation of the instrument and the testing time was used to
      estimate the cost, while reimbursements are based on the 2013 Italian National
      Health System ambulatory pricelist. Variables that could influence the model are
      considered in the sensitivity analyses. The mean cost for C13--Urea, Lactulose
      and Lactose BT are, respectively, Euros 30,59; 45,20 and 30,29. National
      reimbursement often doesn't cover the cost of the analysis, especially
      considering the scenario with lower number of exam. On the contrary, in high
      performance scenario all the reimbursement could cover the cost, except for the
      C13 Urea BT that is high influenced by the drugs cost. However, consideration
      about the difference between Italian Regional Health System ambulatory pricelist
      are done. Our analysis shows that while national reimbursement rates cover the
      costs of H2 breath testing, they do not cover sufficiently C13 BT, particularly
      urea breath test. The real economic strength of these non invasive tests should
      be considered in the overall organization of inpatient and outpatient clinic,
      accounting for complete diagnostic pathway for each gastrointestinal disease.

PMID- 24443076
TI  - Filtration is a time-efficient option to Histopaque, providing good-quality
      islets in mouse islet isolation.
AB  - Pancreatic islet transplantation is a promising therapy for Type I Diabetes. For
      many years the method used worldwide for islet purification in both rodent and
      human islet isolation has been Ficoll-based density gradients, such as
      Histopaque. However, it is difficult to purify islets in laboratories with staff
      limitations when large scale isolations are required. We hypothesized that
      filtration could be a more simple and fast alternative to obtain good quality
      islets. Four separate islet isolations were performed per method, comparing
      filtration and Histopaque purification with handpicking as the gold standard
      method for islet purity. Different parameters of quality were assessed: yield in
      number of islets per pancreas, purity by dithizone staining, viability by
      Fluorescein Diacetate/Propidium Iodide vital staining and in vitro functionality
      assessed by Glucose Stimulated Insulin Secretion. Time efficiency and cost were
      also analyzed. The overall quality of the islets obtained both by Histopaque and
      filtration was good. Filtration saved almost 90 % of the time consumed by
      Histopaque purification, and was also cheaper. However, one-third of the islets
      were lost. Since human and rodent islets share similar size but different
      density, filtration appears as a purification method with potential interest in
      translation to clinic. 

PMID- 24443077
TI  - Dynamic assessment of cell viability, proliferation and migration using real time
      cell analyzer system (RTCA).
AB  - Cell viability and cell migration capacities are critical parameters for cell
      culture-related studies. It is essential to monitor the dynamic changes of cell
      properties under various co-culture conditions to our better understanding of
      their behaviours and characteristics. The real time cell analyzer (RTCA,
      xCELLigence, Roche) is an impedance-based technology that can be used for label
      free and real-time monitoring of cell properties, such as cell adherence,
      proliferation, migration and cytotoxicity. The practicality of this system has
      been proven in our recent cancer studies. In the present method, we intend to use
      co-cultures of pancreatic cancer cells (HP62) and mesenchymal stem cells to
      describe in detail, the procedures and benefits of RTCA. 

PMID- 24443078
TI  - A chemical tool for in vitro and in vivo precipitation of lysine
      methyltransferase G9a.
AB  - Here we report the design, synthesis, and biochemical characterization of a new
      chemical tool, UNC0965. UNC0965 is a biotinylated version of our previously
      reported G9a chemical probe, UNC0638. Importantly, UNC0965 maintains high in
      vitro potency and is cell penetrant. The biotinylated tag of UNC0965 enables
      "chemiprecipitation" of G9a from whole cell lysates. Further, the cell penetrance
      of UNC0965 allowed us to explore the localization of G9a on chromatin both in
      vitro and in vivo through chemical inhibitor-based chromatin immunoprecipitation
      (chem-ChIP). 

PMID- 24443080
TI  - Polypeptides of photosystem II and their role in oxygen evolution.
AB  - The linear, four-step oxidation of water to molecular oxygen by photosystem II
      requires cooperation between redox reactions driven by light and a set of redox
      reactions involving the S-states within the oxygen-evolving complex. The
      oxygenevolving complex is a highly ordered structure in which a number of
      polypeptides interact with one another to provide the appropriate environment for
      productive binding of cofactors such as manganese, chloride and calcium, as well
      as for productive electron transfer within the photoact. A number of recent
      advances in the knowledge of the polypeptide structure of photosystem II has
      revealed a correlation between primary photochemical events and a 'core' complex
      of five hydrophobic polypeptides which provide binding sites for chlorophyll a,
      pheophytin a, the reaction center chlorophyll (P680), and its immediate donor,
      denoted Z. Although the 'core' complex of photosystem II is photochemically
      active, it does not possess the capacity to evolve oxygen. A second set of
      polypeptides, which are water-soluble, have been discovered to be associated with
      photosystem II; these polypeptides are now proposed to be the structural elements
      of a special domain which promotes the activities of the loosely-bound cofactors
      (manganese, chloride, calcium) that participate in oxygen evolution activity. Two
      of these proteins (whose molecular weights are 23 and 17 kDa) can be released
      from photosystem II without concurrent loss of functional manganese; studies on
      these proteins and on the membranes from which they have been removed indicate
      that the 23 and 17 kDa species from part of the structure which promotes
      retention of chloride and calcium within the oxygen-evolving complex. A third
      water-soluble polypeptide of molecular weight 33 kDa is held to the photosystem
      II 'core' complex by a series of forces which in some circumstances may include
      ligation to manganese. The 33 kDa protein has been studied in some detail and
      appears to promote the formation of the environment which is required for optimal
      participation by manganese in the oxygen evolving reaction. This minireview
      describes the polypeptides of photosystem II, places an emphasis on the current
      state of knowledge concerning these species, and discusses current areas of
      uncertainty concerning these important polypeptides. 

PMID- 24443079
TI  - Developmental models for estimating ecological responses to environmental
      variability: structural, parametric, and experimental issues.
AB  - Developmental models that account for the metabolic effect of temperature
      variability on poikilotherms, such as degree-day models, have been widely used to
      study organism emergence, range and development, particularly in agricultural and
      vector-borne disease contexts. Though simple and easy to use, structural and
      parametric issues can influence the outputs of such models, often substantially.
      Because the underlying assumptions and limitations of these models have rarely
      been considered, this paper reviews the structural, parametric, and experimental
      issues that arise when using degree-day models, including the implications of
      particular structural or parametric choices, as well as assumptions that underlie
      commonly used models. Linear and non-linear developmental functions are compared,
      as are common methods used to incorporate temperature thresholds and calculate
      daily degree-days. Substantial differences in predicted emergence time arose when
      using linear versus non-linear developmental functions to model the emergence
      time in a model organism. The optimal method for calculating degree-days depends
      upon where key temperature threshold parameters fall relative to the daily
      minimum and maximum temperatures, as well as the shape of the daily temperature
      curve. No method is shown to be universally superior, though one commonly used
      method, the daily average method, consistently provides accurate results. The
      sensitivity of model projections to these methodological issues highlights the
      need to make structural and parametric selections based on a careful
      consideration of the specific biological response of the organism under study,
      and the specific temperature conditions of the geographic regions of interest.
      When degree-day model limitations are considered and model assumptions met, the
      models can be a powerful tool for studying temperature-dependent development. 

PMID- 24443081
TI  - High CO2 partial pressure effects on dark and light CO2 fixation and metabolism
      in Vicia faba leaves.
AB  - Stomatal opening on Vicia faba can be induced by high CO2 partial pressures
      (10.2%) in dark as well as in light. Stomatal aperture was measured in both cases
      with a hydrogen porometer. The distribution of (14)C among early products of
      photosynthesis was studied. Comparisons are made with carboxylations occurring
      when stomata were open in the dark with CO2-free air and in light with 0.034%
      CO2. Results showed that in high CO2 partial pressure in light, less
      radioactivity was incorporated in Calvin cycle intermediates and more in sucrose.
      beta carboxylations and photorespiration seemed to be inhibited. In the dark in
      both CO2 conditions, (14)C incorporation was found in malate and aspartate but
      also in serine and glycerate in high CO2 conditions. In light these changes in
      metabolic pathways may be related with the deleterious effects recorded on leaves
      after long-term expositions to high partial pressure of CO2. 

PMID- 24443082
TI  - Leaf gas exchange of upland and lowland rice cultivars.
AB  - Leaf gas exchange of upland and lowland rice cultivars were measured during late
      vegetative and during grain filling stages in the field under upland and lowland
      growth conditions. The rate of photosynthesis and water use efficiency (the rate
      of photosynthesis/the rate of transpiration) under upland conditions decreased
      with ageing, but generally varied little among four cultivars. At mid-grain
      filling under lowland conditions, upland cultivars showed lower rates of
      photosynthesis and transpiration than the lowland cultivars with concomitant
      reduction in whole plant conductance. At this stage, water use efficiency was
      higher under upland conditions than under lowland conditions, particularly in the
      upland cultivars. Water stress reduced the rate of photosynthesis without
      altering water use efficiency. 

PMID- 24443083
TI  - Stomatal response to air humidity and its relation to stomatal density in a wide
      range of warm climate species.
AB  - The gas exchange of 19 widely different warm climate species was observed at
      different leaf to air vapour pressure deficits (VPD). In all species stomata
      tended to close as VPD increased resulting in a decrease in net photosynthesis.
      The absolute reduction in leaf conductance per unit increase in VPD was greatest
      in those species which had a large leaf conductance at low VPDs. This would be
      expected even if stomata of all species were equally sensitive. However the
      percentage reduction in net photosynthesis (used as a measure of the relative
      sensitivity of stomata of the different species) was also closely related to the
      maximal conductance at low VPD. Similarily the relative sensitivity of stomata to
      changes in VPD was closely related to the weighted stomatal density or 'crowding
      index'.The hypothesis is presented that stomatal closure at different VPDs is
      related to peristomatal evaporation coupled with a high resistance between the
      epidermis and the mesophyll and low resistance between the stomatal apparatus and
      the epidermal cells. This hypothesis is consistent with the greater relative
      sensitivity of stomata on leaves with a high crowding index.The results and the
      hypothesis are discussed in the light of selection, for optimal productivity
      under differing conditions of relative humidity and soil water availablility, by
      observation of stomatal density and distribution on the two sides of the leaf. 

PMID- 24443084
TI  - The antenna system of Rhodospirillum rubrum. Detection of macromolecular
      constituents not stainable by Coomassie brilliant blue in solubilized
      preparations of the B880 complex.
AB  - A solubilized preparation of the major Rhodospirillum rubrum antenna complex
      (B880) was obtained by a described procedure and its polypeptide composition was
      analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl
      sulfate. Only two polypeptides of molecular weights close to 7000 were detected
      after staining the gels with Coomassie brilliant blue. However, several other
      constituents could be visualized by silver staining or by an immunochemical
      method. When the preparation was chromatographed on Sephacryl, some of the
      resulting fractions exhibited the characteristic B880 absorption spectrum and
      contained only the two proteins that were detectable with Coomassie brilliant
      blue. In those fractions the A 280/A 880ratio was 0.4, which indicated a
      significant improvement of the bacteriochlorophyll to protein ratio over the
      unchromatographed preparation (A 280/A 880=0.7). Other chromatography fractions
      lacked bacteriochlorophyll and contained a carotenoid which seemed to be bound to
      protein. The macromolecular constituents present in these latter fractions
      differed from those associated to the purified B880 complex in their
      electrophoretic moblities and/or in their staining properties. That suggested the
      possible existence of a carotenoprotein that did not result from the B880 complex
      upon loss of bacteriochlorophyll. 

PMID- 24443085
TI  - Steady-state room temperature fluorescence and CO2 assimilation rates in intact
      leaves.
AB  - Steady-state room temperature variable fluorescence from leaves was measured as a
      function of CO2 pressure in Xanthium strumarium L. and Phaseolus vulgaris L.
      Measurements were made in a range of light intensities, at normal and low O2
      parital pressure and over a range of temperatures.At low CO2 pressure
      fluorescence increased with increasing CO2. At higher CO2 pressure fluorescence
      usually decreased with increasing CO2 but occasionally increased slightly. The
      transition CO2 pressure between the responses could be changed by changing light,
      O2 pressure, or temperature. This breakpoint in the fluorescence-CO2 curve was a
      reliable indicator of the transition between ribulose 1,5-bisphosphate (RuBP)
      saturated assimilation and RuBP regeneration limited assimilation. The
      fluorescence signal was not a reliable indicator of O2-insensitive assimilation
      in these C3 species. 

PMID- 24443086
TI  - Photosynthetic inhibition after long-term exposure to elevated levels of
      atmospheric carbon dioxide.
AB  - The effect of long-term exposure to elevated levels of CO2 on biomass
      partitioning, net photosynthesis and starch metabolism was examined in cotton.
      Plants were grown under controlled conditions at 350, 675 and 1000 MUl l(-1) CO2.
      Plants grown at 675 and 1000 MUl l(-1) had 72% and 115% more dry weight
      respectively than plants grown at 350 MUl l(-1). Increases in weight were
      partially due to corresponding increases in leaf starch. CO2 enrichment also
      caused a decrease in chlorophyll concentration and a change in the chlorophyll
      a/b ratio. High CO2 grown plants had lower photosynthetic capacity than 350 MUl
      l(-1) grown plants when measured at each CO2 concentration. Reduced
      photosynthetic rates were correlated with high internal (non-stomatal)
      resistances and higher starch levels. It is suggested that carbohydrate
      accumulation causes a decline in photosynthesis by feedback inhibition and/or
      physical damage at the chloroplast level. 

PMID- 24443087
TI  - Characteristics of the relative maximum in the decay of delayed light emission
      from Pothos leaf following far-red excitation.
AB  - Following illumination with wavelengths longer than 700 nm, the intensity of
      light emission from Pothos aurea leaf falls for 1 min and then increases to a
      maximum after 2 min in the dark. The spectrum of this minute-range liminescence
      matches that of prompt fluorescence excited at the same wavelength, but differs
      from that of prompt or minute-range delayed emission excited by wavelengths
      shorter than 700 nm. This emission is less sensitive to heat damage than
      millisecond delayed emission, and may originate from photosystem I. 

PMID- 24443088
TI  - A soluble chloroplast protein catalyzes ribulosebisphosphate
      carboxylase/oxygenase activation in vivo.
AB  - Ribulosebisphosphate carboxylase/oxygenase (EC 4.1.1.39) (rubisco) must be fully
      activated in order to catalyze the maximum rates of photosynthesis observed in
      plants. Activation of the isolated enzyme occurs spontaneously, but conditions
      required to observe full activation are inconsistent with those known to occur in
      illuminated chloroplasts. Genetic studies with a nutant of Arabidopsis thaliana
      incapable of activating rubisco linked two chloroplast polypeptides to the
      activation process in vivo. Using a reconstituted light activation system, it was
      possible to demonstrate the participation of a chloroplast protein in rubisco
      activation. These results indicate that a specific chloroplast enzyme, rubisco
      activase, catalyzes the activation of rubisco in vivo. 

PMID- 24443089
TI  - Response practices in multilingual interaction with an older Persian woman in a
      Swedish residential home.
AB  - In the present case study, a care encounter between an older multilingual
      (Farsi/Swedish/English) Persian woman and staff in an ordinary, Swedish
      residential home is investigated. The woman is perceived as suffering from
      dementia symptoms, but has not received any formal diagnosis of the disease. More
      specifically, the study focuses on how the woman's contributions in her mother
      tongue, Farsi, are responded to by a carer, who is also multilingual and speaks
      Swedish as a second language (L2), but has a very limited knowledge of Farsi. The
      data consists of recorded material from a mundane morning activity in the
      residential home, as the woman is undressed and prepared to go to the shower. The
      method employed is conversation analysis, and the study addresses the
      interactional outcome of this type of multilingual encounters, highlighting the
      way the establishment of mutual understanding is negatively affected by the fact
      that the participants do not or only to a limited extent share a common language.
      Analysis of the data shows that most of the woman's contributions in Farsi are
      responded to in L2-Swedish by the carer, primarily by means of seven different
      response practices: soothing talk, instrumental talk, minimal responses, explicit
      expressions of understanding, mitigating talk, questions, and appraisal. The
      findings are discussed in light of new demands on Swedish (and Western) care- and
      health care systems to adapt to the increasing number of multilingual, older
      people, who will become residents in care facilities and attend day centers
      within the coming years. 

PMID- 24443090
TI  - Comparison of monovalent and divalent ion distributions around a DNA duplex with
      molecular dynamics simulation and a Poisson-Boltzmann approach.
AB  - The ion atmosphere created by monovalent (Na(+) ) or divalent (Mg(2+) ) cations
      surrounding a B-form DNA duplex were examined using atomistic molecular dynamics
      (MD) simulations and the nonlinear Poisson-Boltzmann (PB) equation. The ion
      distributions predicted by the two methods were compared using plots of radial
      and two-dimensional cation concentrations and by calculating the total number of
      cations and net solution charge surrounding the DNA. Na(+) ion distributions near
      the DNA were more diffuse in PB calculations than in corresponding MD
      simulations, with PB calculations predicting lower concentrations near DNA groove
      sites and phosphate groups and a higher concentration in the region between these
      locations. Other than this difference, the Na(+) distributions generated by the
      two methods largely agreed, as both predicted similar locations of high Na(+)
      concentration and nearly identical values of the number of cations and the net
      solution charge at all distances from the DNA. In contrast, there was greater
      disagreement between the two methods for Mg(2+) cation concentration profiles, as
      both the locations and magnitudes of peaks in Mg(2+) concentration were
      different. Despite experimental and simulation observations that Mg(2+) typically
      maintains its first solvation shell when interacting with nucleic acids, modeling
      Mg(2+) as an unsolvated ion during PB calculations improved the agreement of the
      Mg(2+) ion atmosphere predicted by the two methods and allowed for values of the
      number of bound ions and net solution charge surrounding the DNA from PB
      calculations that approached the values observed in MD simulations.

PMID- 24443092
TI  - Parent preferences regarding stimulant therapies for ADHD: a comparison across
      six European countries.
AB  - The objective is to identify attributes of ADHD stimulant medications that
      influence treatment preferences of parents of children and adolescents with ADHD
      across six European countries, using a discrete choice experiment (DCE).
      Different attributes (and associated levels) of stimulant therapies were
      identified through literature review and clinician input. Attributes included
      duration and degree of symptom control after each dose, frequency of medication
      dosing, potential for treatment to be abused, the side effects of vomiting, loss
      of appetite, and sleep disturbance. Attributes and levels were combined using an
      orthogonal design to produce a number of discrete hypothetical treatments.
      Parents were recruited via patient panels in different countries and asked to
      complete a survey. DCE data were analyzed using conditional logit models to
      explore the impact of each attribute on participants' choices. Six hundred
      individuals (220 parents of adolescents and 380 parents of children)
      participated. All attributes were significant predictors of choice (p < 0.01).
      'Degree of symptom control' was the most important attribute whereby the odds of
      choosing 'very much improved symptoms' compared with 'minimally improved' was
      4.85 [95 % confidence interval (CI) = 4.28-5.49] for the adolescent group and
      6.37 (95 % CI = 5.79-7.01) for the child group. Some inter-country differences
      emerged, e.g., achieving the best degree of symptom control was more important to
      parents in some countries than others. In conclusion, the study showed that
      duration and degree of symptom control were the most important aspects of
      treatment for parents in all countries. The findings revealed cultural
      differences in the relative importance of attributes.

PMID- 24443093
TI  - Early endoscopic dilation and mitomycin application in the treatment of acquired
      tracheal stenosis.
AB  - INTRODUCTION: Acquired airway stenosis is a common complication in children after
      periods of tracheal intubation. We reviewed our experience in the endoscopic
      treatment of these lesions. PATIENTS AND METHODS: We performed a retrospective
      review of patients who presented acquired tracheal-subglottic stenosis (SGS)
      treated at our center from 2005 to 2012. We reviewed the etiology, age, clinical
      presentation, methods of diagnosis, number of bronchoscopies, angioplasty balloon
      dilations performed, and long-term results. RESULTS: A total of 18 patients (13
      M, 5 F) were treated at our institution between 2005 and 2012. Median age at
      treatment was 3.5 months (range, 1-96 months). Of the 18 children, 16 children
      had SGS (all cases were postintubation), and 2 children presented tracheal
      stenosis (1 postintubation, 1 after tracheal surgery). Median intubation time was
      30 days (range, 3-120 days). Extubation failure and stridor were the main
      clinical features. SGS were diagnosed as grade I in three patients, grade II in
      nine patients, and grade III in six patients. Bronchoscopy allowed diagnostic in
      all cases, and was followed by angioplasty balloon dilation, with a median of 2.5
      (range, 1-5) sessions. In SGS grade I, the relation patient/number of dilations
      was 1; in SGS grade II 2.6, and in SGS grade III 3.5. Mitomycin was applied in 15
      patients. No patients presented intraoperative complications or required
      reoperation. Median follow-up time was 36 months (range, 5-72 months) and no
      recurrence was noticed. CONCLUSIONS: Early endoscopic dilation with balloon shows
      as an effective and safe treatment in acquired tracheal and SGS.

PMID- 24443091
TI  - Shape abnormalities of subcortical and ventricular structures in mild cognitive
      impairment and Alzheimer's disease: detecting, quantifying, and predicting.
AB  - This article assesses the feasibility of using shape information to detect and
      quantify the subcortical and ventricular structural changes in mild cognitive
      impairment (MCI) and Alzheimer's disease (AD) patients. We first demonstrate
      structural shape abnormalities in MCI and AD as compared with healthy controls
      (HC). Exploring the development to AD, we then divide the MCI participants into
      two subgroups based on longitudinal clinical information: (1) MCI patients who
      remained stable; (2) MCI patients who converted to AD over time. We focus on
      seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus
      pallidus, and lateral ventricles) in 754 MR scans (210 HC, 369 MCI of which 151
      converted to AD over time, and 175 AD). The hippocampus and amygdala were further
      subsegmented based on high field 0.8 mm isotropic 7.0T scans for finer
      exploration. For MCI and AD, prominent ventricular expansions were detected and
      we found that these patients had strongest hippocampal atrophy occurring at CA1
      and strongest amygdala atrophy at the basolateral complex. Mild atrophy in basal
      ganglia structures was also detected in MCI and AD. Stronger atrophy in the
      amygdala and hippocampus, and greater expansion in ventricles was observed in MCI
      converters, relative to those MCI who remained stable. Furthermore, we performed
      principal component analysis on a linear shape space of each structure. A
      subsequent linear discriminant analysis on the principal component values of
      hippocampus, amygdala, and ventricle leads to correct classification of 88% HC
      subjects and 86% AD subjects.

PMID- 24443094
TI  - Experience of the MACE procedure at a regional pediatric surgical unit: a 15-year
      retrospective review.
AB  - INTRODUCTION: The Malone antegrade continence enema (MACE) procedure is an
      established treatment option for children with constipation or fecal
      incontinence. This study retrospectively analyses the management and outcomes of
      children who underwent MACE procedures at a regional pediatric surgery unit.
      PATIENTS AND METHODS: Children who underwent a MACE procedure in our unit between
      1998 and 2012 were identified. Demographic and clinical data were obtained from
      contemporaneous records. Using the continence scale described by Malone, overall
      outcomes were categorized as full, partial, or failure (full: totally clean or
      minor rectal leakage on night of washout; partial: clean but significant stoma or
      rectal leakage, occasional major leak and/or still wearing protection but
      perceived by child or parent to be an improvement; failure: regular soiling or
      constipation persisted, no perceived improvement, procedure was abandoned). Data
      entry and statistical analysis were performed using Excel and SPSS (IBM Corp.,
      Armonk, New York, United States). RESULTS: A total of 40 children (29 male) were
      identified for inclusion. Underlying diagnoses were idiopathic constipation (16),
      anorectal anomalies (14) and Hirschprung's disease (10). The MACE procedure was
      performed laparoscopically in 26 cases and using an open technique in 14 cases.
      Mean age at the time of surgery was 8.9 years (range, 3-19 years) and mean follow
      up time was 6.5 years (range, 1-10 years). Outcomes categorized as full were
      62.5% for chronic idiopathic constipation (CIC), 71.4% for anorectal malformation
      (ARM), and 70% for Hirschsprung disease (HD). Overall success rates (full and
      partial outcomes combined) were 87.5% for CIC, 92.8% for ARM, 100% for HD, and
      92.5% for all diagnoses taken together. Eleven MACE procedures (27.5%) were
      reversed, in seven (17.5%) due to the return of spontaneous and regular bowel
      movements and in four (10%) due to stomal problems. CONCLUSION: This study
      identified a high success rate (combining full and partial outcomes) of 92.5% for
      MACE procedures within our unit. An encouraging finding is that the procedure was
      reversed in a significant proportion of patients following the return of normal
      bowel habits.

PMID- 24443095
TI  - Video-assisted thoracoscopic anterior surgery combined posterior instrumentation
      for children with spinal tuberculosis.
AB  - BACKGROUND: The use of thoracoscopy for the treatment of spinal disorders has
      been applied mostly in adults. However, thoracoscopic decompression of spinal
      tuberculosis in children has probably been rarely documented. OBJECTIVE: To
      assess the efficacy of video-assisted thoracoscopic anterior surgery (VATS)
      combined with posterior instrumentation for children with spinal tuberculosis.
      STUDY DESIGN: Total 15 consecutive children with spinal tuberculosis with VATS
      combined with posterior instrumentation were included. METHODS: Overall 15 cases
      of spinal tuberculosis were treated with the procedure of posterior internal
      fixation and anterior debridement by VATS combined with posterior instrumentation
      between January 2002 and December 2006.There were nine males and six females with
      an average age of 11.6 years (8-15 y). All patients were given appropriate
      chemotherapy for 4 to 12 weeks preoperatively and 12 to 15 months
      postoperatively. All patients were followed up with evaluation of the changes of
      kyphotic deformity noted. RESULTS: All the cases were followed up over an average
      of 37.3 months (range, 12-48 mo).The wounds were healed without chronic infection
      or sinus formation. Four patients improved three grades, two patients improved
      two grades, and seven patients improved one grade. The average neurological
      recovery in the patients was 1.44 grades on the scale by Frankel et al. The
      average preoperative kyphosis was 37 degrees (range, 23-59 degrees) and the
      average postoperative kyphosis was 25 degrees (range, 18-35 degrees) at final
      follow-up. Also, minimal progression of kyphosis was seen at final follow-up with
      an average kyphosis of 28 degrees (range, 20-40 degrees); and average loss of
      correction of 3 degree was seen at final follow-up. CONCLUSIONS: VATS combined
      with posterior instrumentation achieve satisfactory results for children with
      spinal tuberculosis.

PMID- 24443096
TI  - Less is more: new biomimetic approach to control spatial and temporal cell
      loading for tissue engineering.
AB  - It is increasingly recognized that use of stiff biodegradable polymers in
      connective tissue engineering has an inherent flaw. Although polymer stiffness
      has early benefit for mechanical strength of implants, such pseudoprosthetic
      material function inevitably stress shields embedded cells, switching off their
      synthetic/remodeling functions. This core conundrum represents a tension between
      early mechanical benefits of polymer stiffness against blocking of cell load
      dependent matrix production. In effect, an ideal system would produce a gradual,
      transfer of load onto resident cells and their matrix. Toward this target, our
      "less is more" (LiM) hypothesis proposes that less stress shielding (polymer
      stiffness) will lead to more cell-dependent tissue formation. To test this we
      have designed a hybrid segregation solution in which the cells are segregated
      into a native (but weak) collagen-gel matrix while the external mechanical
      loading is taken by temporary, reinforcing polyglycolic acid (PGA) fibers, with
      gradual, load transfer as the polymer u-fibers fracture. Dermal fibroblasts grew
      predictably in the hybrid construct and the fine, parallel PGA fibers fractured
      and fragmented due to hydrolysis, giving a fall of construct stiffness to near
      collagen-only levels, over 14 days. The same fiber fracture and fall in stiffness
      occurred over 14 days in constructs implanted in vivo. In this case a cell
      dependent, net enhancement of connective tissue stiffness could be identified in
      hybrid constructs, supporting the LiM hypothesis for cytomechanical control of
      matrix. This is the first demonstration of spatiotemporal load transfer as a
      customizable tool for improved, biomimetic connective tissue engineering.

PMID- 24443097
TI  - The relevance of the philosophical 'mind-body problem' for the status of
      psychosomatic medicine: a conceptual analysis of the biopsychosocial model.
AB  - Psychosomatic medicine, with its prevailing biopsychosocial model, aims to
      integrate human and exact sciences with their divergent conceptual models.
      Therefore, its own conceptual foundations, which often remain implicit and
      unknown, may be critically relevant. We defend the thesis that choosing between
      different metaphysical views on the 'mind-body problem' may have important
      implications for the conceptual foundations of psychosomatic medicine, and
      therefore potentially also for its methods, scientific status and relationship
      with the scientific disciplines it aims to integrate: biomedical sciences
      (including neuroscience), psychology and social sciences. To make this point, we
      introduce three key positions in the philosophical 'mind-body' debate
      (emergentism, reductionism, and supervenience physicalism) and investigate their
      consequences for the conceptual basis of the biopsychosocial model in general and
      its 'psycho-biological' part ('mental causation') in particular. Despite the
      clinical merits of the biopsychosocial model, we submit that it is conceptually
      underdeveloped or even flawed, which may hamper its use as a proper scientific
      model. 

PMID- 24443098
TI  - Consequences of age on ischemic wound healing in rats: altered antioxidant
      activity and delayed wound closure.
AB  - Advertisements targeted at the elderly population suggest that antioxidant
      therapy will reduce free radicals and promote wound healing, yet few scientific
      studies substantiate these claims. To better understand the potential utility of
      supplemental antioxidant therapy for wound healing, we tested the hypothesis that
      age and tissue ischemia alter the balance of endogenous antioxidant enzymes.
      Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created
      on young and aged rats. Wound closure and the balance of the critical
      antioxidants superoxide dismutase and glutathione in the wound bed were
      determined. Ischemia delayed wound closure significantly more in aged rats. Lower
      superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats
      indicate a basal deficit due to age alone. Ischemic wounds from aged rats had
      lower superoxide dismutase 2 protein and activity initially, coupled with
      decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase
      activity. De novo glutathione synthesis, to restore redox balance in aged
      ischemic wounds, was initiated as evidenced by increased glutamate cysteine
      ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats
      that become exaggerated in ischemic tissue, culminating in profoundly impaired
      wound healing and prolonged inflammation. 

PMID- 24443100
TI  - Engraving copper foil to give large-scale binder-free porous CuO arrays for a
      high-performance sodium-ion battery anode.

PMID- 24443099
TI  - Effect of COMT Val108/158Met genotype on risk for polydipsia in chronic patients
      with schizophrenia.
AB  - Polydipsia is a serious condition often seen among patients with schizophrenia
      (SCZ). The cause of polydipsia is unknown; hence, it is hard to treat or manage.
      Animal studies showed that the drinking behavior is regulated by central
      dopaminergic neurotransmission at the hypothalamus. Meanwhile, the existence of a
      genetic predisposition to polydipsia in patients with SCZ has been suggested. The
      purpose of this study was to assess whether a functional polymorphism,
      Val(108/158)Met in the gene for catechol-O-methyltransferase (COMT), is
      associated with susceptibility to polydipsia using a Japanese sample of SCZ. Our
      sample includes 330 chronic patients with SCZ (83 polydipsic patients and 247 non
      polydipsic controls). The common COMT Val(108/158)Met polymorphism was genotyped,
      and the differences in genotype distribution and allele frequency between cases
      and controls were evaluated using the chi(2) test. A significant association
      between the COMT Val(108/158)Met polymorphism and polydipsia was found (genotype
      distribution: chi(2) = 13.0, df = 2, p = 0.001; allele frequency: chi(2) = 7.50,
      df = 1, p = 0.006). The high-COMT activity group (Val/Val) was more frequent
      among patients with polydipsia compared with the low-COMT activity group (Val/Met
      + Met/Met) [odds ratio (OR) = 2.46]. The association survived after controlling
      for other possible confounding factors, including gender, age, age of onset,
      current antipsychotic dose, and smoking status. Our results suggest that the COMT
      Val(108/158)Met genotype may confer susceptibility to polydipsia in SCZ. To our
      knowledge, this is the first association study between the COMT gene and
      polydipsia in SCZ. Further studies with larger sample sizes are warranted to
      confirm present findings.

PMID- 24443102
TI  - Modeling the residue function in DSC-MRI simulations: analytical approximation to
      in vivo data.
AB  - PURPOSE: An exponential residue function is commonly used in numerical
      simulations to assess the accuracy of perfusion quantification using dynamic
      susceptibility contrast (DSC) MRI. Although this might be a reasonable assumption
      for normal tissue, microvascular hemodynamics are likely to be significantly
      altered in pathology. Thus the exponential function may no longer be appropriate
      and the estimated accuracy of DSC-MRI quantification might be inappropriate. The
      purpose of this study was to characterize in vivo residue function variations in
      normal and infarcted tissue in a chronic atherosclerotic disease cohort, and to
      find the most appropriate model for use in DSC simulations. METHODS: Residue
      functions were measured in vivo in patients with atherosclerotic disease using a
      nonparametric Control Point Interpolation method, which has been shown to provide
      a robust characterization of the shape of the residue function. The observed
      residue functions were approximated with five commonly used analytical
      expressions: exponential, bi-exponential, Lorentzian, and Fermi functions, and a
      previously proposed Vascular Model. RESULTS: The lowest error was found with the
      bi-exponential function approximations to the in vivo residue functions from both
      normal and infarcted tissue. CONCLUSION: A bi-exponential model should therefore
      be used in future numerical simulations of DSC-MRI instead of the exponential
      function.

PMID- 24443101
TI  - Advancing the prevention agenda for HIV and other sexually transmitted infections
      in south China: social science research to inform effective public health
      interventions.
AB  - Despite widespread biomedical advances in treatment and prevention, HIV and other
      sexually transmitted infections (STI) continue to affect a large portion of the
      world's population. The profoundly social nature of behaviorally driven epidemics
      and disparities across socioeconomic divides in the distribution of HIV/STI and
      care outcomes emphasize the need for innovative, multilevel interventions.
      Interdisciplinary approaches to HIV/STI control are needed to combine insights
      from the social and biological sciences and public health fields. In this
      concluding essay to a Special Issue on HIV/STI in south China, we describe the
      evolution of the region's HIV/STI epidemics and the government response, then
      synthesize findings from the 11 studies presented in this issue to extend seven
      recommendations for future HIV/STI prevention and care research in China. We
      discuss lessons learned from forging international collaborations between the
      social and biological sciences and public health to inform a shared research
      agenda to better meet the needs of those most affected by HIV and other STI.

PMID- 24443103
TI  - Transition-metal-catalyzed C-S bond coupling reaction.
AB  - Sulfur-containing molecules such as thioethers are commonly found in chemical
      biology, organic synthesis, and materials chemistry. While many reliable methods
      have been developed for preparing these compounds, harsh reaction conditions are
      usually required in the traditional methods. The transition metals have been
      applied in this field, and the palladium-catalyzed coupling of thiols with aryl
      halides and pseudo halides is one of the most important methods in the synthesis
      of thioethers. Other metals have also been used for the same purpose. Here, we
      summarize recent efforts in metal-catalyzed C-S bond cross-coupling reactions,
      focusing especially on the coupling of thiols with aryl- and vinyl halides based
      on different metals.

PMID- 24443104
TI  - Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals
      an endocrine signature.
AB  - Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of liver cancer
      occurring mostly in children and young adults. We have shown that FLC comprises
      two separate entities: pure (p-FLC) and mixed-FLC (m-FLC), differing in clinical
      presentation and course. We show that p-FLCs have a distinct gene expression
      signature different from that of m-FLCs, which have a signature similar to that
      of classical hepatocellular carcinomas. We found p-FLC profiles to be unique
      among 263 profiles related to diverse tumoral and nontumoral liver samples. We
      identified two distinct molecular subgroups of p-FLCs with different outcomes.
      Pathway analysis of p-FLCs revealed ERBB2 overexpression and an up-regulation of
      glycolysis, possibly leading to compensatory mitochondrial hyperplasia and
      oncocytic differentiation. Four of the sixteen genes most significantly
      overexpressed in p-FLCs were neuroendocrine genes: prohormone convertase 1
      (PCSK1); neurotensin; delta/notch-like EGF repeat containing; and calcitonin.
      PCSK1 overexpression was validated by immunohistochemistry, yielding specific,
      diffuse staining of the protein throughout the cytoplasm, possibly corresponding
      to a functional form of this convertase. CONCLUSION: p-FLCs have a unique
      transcriptomic signature characterized by the strong expression of specific
      neuroendocrine genes, suggesting that these tumors may have a cellular origin
      different from that of HCC. Our data have implications for the use of genomic
      profiling for diagnosis and selection of targeted therapies in patients with p
      FLC.

PMID- 24443105
TI  - Tracheal intubation with a flexible intubation scope versus other intubation
      techniques for obese patients requiring general anaesthesia.
AB  - BACKGROUND: The prevalence of obesity (body mass index (BMI) > 30 kg/m(2)) is
      increasing in both developed and developing countries, leading to a rise in the
      numbers of obese patients requiring general anaesthesia. Obese patients are at
      increased risk of anaesthetic complications, and tracheal intubation can be more
      difficult. Flexible intubation scopes (FISs) are recommended as an alternative
      method of intubation in these patients. Intubation with an FIS is considered an
      advanced method, requiring training and experience; therefore it may be underused
      in clinical practice. Patient outcomes following intubation with these scopes
      compared with other devices have not been systematically reviewed. OBJECTIVES: We
      wished to compare the safety and effectiveness of a flexible intubation scope
      (FIS) used for tracheal intubation in obese patients (BMI > 30 kg/m(2)) with
      other methods of intubation, including conventional direct laryngoscopy, non
      standard laryngoscopy and the use of intubating supraglottic airway devices. We
      aimed to compare the frequency of complications, as well as process indicators,
      such as time taken for intubation and the proportion of first attempts that were
      successful, between groups using the different methods of intubation. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE and two trial registers on 18 January 2013, and
      performed reference checking and citation searching and contacted study authors
      to identify additional studies. SELECTION CRITERIA: We included randomized
      controlled trials (RCTs) of participants aged 16 years and older with a BMI > 30
      kg/m(2) that had compared the use of an FIS for tracheal intubation with any one
      of three comparison groups: direct laryngoscopy; non-standard laryngoscopy
      (including indirect laryngoscopy using a videolaryngoscope (VLS) or a rigid or
      semi-rigid stylet); or intubation of supraglottic airway devices (SADs). DATA
      COLLECTION AND ANALYSIS: We used standard methodological approaches expected by
      The Cochrane Collaboration, including independent review of titles, data
      extraction and risk of bias assessment by two investigators. MAIN RESULTS: Three
      eligible studies were identified, all comparing the use of an FIS with a VLS. All
      studies were small, with only 131 participants in total across all trials. It was
      impossible for the intubators to be unaware of the device used, so all studies
      were at high risk of performance and detection bias for outcomes related to
      intubation. Because of substantial differences in design between the studies, we
      did not combine their results in meta-analyses. The results for all outcomes were
      inconclusive, with no differences noted between FIS and VLS. Two studies with
      experienced intubators reported first attempt success rates greater than 70% in
      both groups and less than 5% of participants requiring a change of intubation
      device. No evidence was found of any difference in difficulty or time taken
      between FIS and VLS intubation. No serious complications or airway trauma was
      reported, so we were unable to address these outcomes. Bleeding was uncommon,
      occurring in less than 5% of participants, and we found no evidence that it was
      more likely in the FIS group. One small study with a novice intubator reported no
      successful intubations using an FIS and compared with the use of an intubating
      SAD and stylet, as well as with a VLS. With only five participants in each group,
      no conclusions can be drawn from these additional comparisons. AUTHORS'
      CONCLUSIONS: The evidence base is sparse, and the existing literature does not
      address the clinical questions of patient safety posed by this review. We are
      therefore unable to draw any conclusions on safety or effectiveness. More primary
      research is needed to investigate optimal intubation techniques in obese
      patients, and new studies should be powered to detect differences in
      complications and in success rates rather than process measures such as speed,
      which are of limited clinical importance.

PMID- 24443106
TI  - Medical Students' Evaluation of live Psychiatric Interviews.
AB  - A central concern of psychiatric educators is how medical students learn to
      evaluate psychopathology and clinically relevant behaviors during a psychiatric
      clerkship. The purpose of this study is to determine what characteristics of the
      students studied correlated with their accuracy in rating patient psychopathology
      and also whether the students show improved accuracy in rating after a 6-week
      clerkship in a university medical school department of psychiatry. The study
      analyzes student ratings of various aspects of psychopathology in live patient
      faculty interviews. The accuracy of student ratings compared with faculty ratings
      constitutes the dependent variable. The role of students' attitudes toward
      psychiatry, overall grade performance, and personal background constitute the
      independent variables; these variables are analyzed in relation to the accuracy
      of student ratings. The authors attempt to determine if student ratings improve
      during clerkship. The ability to rate clinical phenomenology in psychiatric
      patients in a live format is shown to be a measurable trait that improves
      slightly over time in some areas and varies in relation to some of the
      independent variables studied. Results of the study are compared with previous
      work in this area. The limitations of the paradigm employed and the requirements
      for studying the problem in a more systematic and effective way are outlined. 

PMID- 24443107
TI  - Recognition of teaching excellence through the use of teaching awards : a faculty
      perspective.
AB  - Teaching as a faculty activity is often undereinphasized in medical faculty
      reward systems for a variety of reasons. One method of recognizing teaching
      excellence has been through annual teaching awards offered by many departments
      and colleges. The authors surveyed department of psychiatry faculty regarding
      teaching awards, particularly questioning whether such awards influence teaching
      behavior or serve a motivational function. The results suggest such awards serve
      an important recognition function, but a lesser motivational function in academic
      psychiatry. 

PMID- 24443108
TI  - Textbooks and software used to teach behavioral science and clinical psychiatry
      to medical students.
AB  - The authors discuss the results of a questionnaire sent to medical schools to
      assess textbooks and computer software used in teaching behavioral science and
      clinical psychiatry. Attributes concerning presentation, theoretical viewpoints,
      and topics covered were rated by 75 respondents. Certain texts emerged as
      frequently used. Although the books rated will become outdated, consumers can use
      the assessment attributes from the questionnaire to examine forthcoming texts.
      Authors considering new books or revisions may want to know why certain books are
      popular and to address areas identified as weak in existing textbooks. The
      software market needs entrees. 

PMID- 24443109
TI  - Outpatient management teams : integrating educational and administrative tasks.
AB  - To provide a more structured experience in outpatient psychiatric training, the
      UCLA Neuropsychiatrie Institute's outpatient department organized outpatient
      management teams. Each team is supervised by a pair of faculty psychiatrists. PGY
      3 and PGY-4 teams also include a psychologist and a social worker. The teams
      serve to provide comprehensive outpatient psychiatric training, track and review
      patients seen by the trainees, and ensure quality of care. In this way, the teams
      have successfully linked educational, clinical, and administrative tasks. The
      authors review the organization and processes of this outpatient program, now in
      its third year. 

PMID- 24443110
TI  - Components of supervisors' ratings of therapists' skillfulness.
AB  - A questionnaire was developed to assess the skillfulness of therapists from the
      perspective of the supervisor. This supervisor report yielded two scores: one for
      psychotherapeutic techniques and one for the educational alliance. These scores
      had high internal consistency and were relatively independent of one another.
      Ratings of proficiency in psychotherapeutic techniques accounted for 54% of the
      variance in supervisors' rating? of global skillfulness; educational alliance
      contributed an additional 12%. Compared with other supervisors, those who
      espoused self psychology based more of their appraisal of skill fulness on the
      trainee's use of the supervisory relationship. 

PMID- 24443111
TI  - Therapist-initiated patient transfer in the residency training setting.
AB  - Therapist-initiated transfers of dynamic psychotherapy patients, precipitated by
      the need for residents to have a broad exposure to varied services, are common
      phenomena in residency training settings. Both the transferring therapist and the
      patient may experience these transfers as distressing. The inexperienced
      therapist may initiate inappropriate transfers, incomplete terminations, or
      social behavior toward the patient. A case example is presented and discussed in
      light of the relevant literature. Recommendations for prophylactic measures
      include education, strong supervisory support to explore countertransference
      issues, and the use of a case conference at points of transfer. 

PMID- 24443114
TI  - Psychiatric Education at the APA Meeting : May 2-7, 1992, Washington,D.C.

PMID- 24443112
TI  - Didactic modules for curricular development in child and adolescent psychiatry
      education.
AB  - A group of child and adolescent psychiatry educators in the Association for
      Academic Psychiatry have developed didactic aids, termed modules,for curricular
      development in child psychiatry training programs. These modules consist of sets
      of references designed to communicate the essence of a subject area. The design
      is flexible, allowing the modules to be used by programs with varying amounts of
      time available for teaching the designated subject. The project has been endorsed
      by the major organizations representing education in child psychiatry. Eight
      modules are available for distribution, and a mechanism is in place for creating
      others. The authors believe this concept will be equally useful in adult
      psychiatry programs. 

PMID- 24443115
TI  - Interventions to enhance informed choices among invitees of screening programmes
      a systematic review.
AB  - BACKGROUND: Informed decision making about participation has become an explicit
      purpose in invitations for screening programmes in western countries. An informed
      choice is commonly defined as based on: (i) adequate levels of knowledge of the
      screening and (ii) agreement between the invitee's values towards own screening
      participation and actual (intention to) participation. METHODS: We systematically
      reviewed published studies that empirically evaluated the effects of
      interventions aiming at enhancing informed decision making in screening
      programmes targeted at the general population. We focused on prenatal screening
      and neonatal screening for diseases of the foetus/new-born and screening for
      breast cancer, cervical cancer and colorectal cancer. The Medline, EMBASE and
      Cochrane databases were searched for studies published till April 2012, using the
      terms 'informed choice', 'decision making' and 'mass screening' separately and in
      combination and terms referring to the specific screening programmes. RESULTS: Of
      the 2238 titles identified, 15 studies were included, which evaluated decision
      aids (DAs), information leaflets, film, video, counselling and a specific
      screening visit for informed decision making in prenatal screening, breast and
      colorectal cancer screening. Most of the included studies evaluated DAs and
      showed improved knowledge and informed decision making. Due to the limited number
      of studies the results could not be synthesized. CONCLUSION: The empirical
      evidence regarding interventions to improve informed decision making in screening
      is limited. It is unknown which strategies to enhance informed decision making
      are most effective, although DAs are promising. Systematic development of
      interventions to enhance informed choices in screening deserves priority,
      especially in disadvantaged groups.

PMID- 24443116
TI  - Role of diffusion-weighted MRI in acute pyelonephritis: a prospective study.
AB  - BACKGROUND: Imaging is vital in diagnosis of complicated pyelonephritis and has
      been traditionally performed by computed tomography (CT). However, CT with
      contrast agents cannot be performed in patients with renal failure. Diffusion
      weighted (DW) magnetic resonance imaging (MRI) has the potential to overcome this
      disadvantage. PURPOSE: To prospectively evaluate the accuracy of quantitative
      apparent diffusion coefficient (ADC) values to differentiate nephritis from renal
      abscesses in patients with pyelonephritis. MATERIAL AND METHODS: Forty-two
      patients with clinical and laboratory diagnosis of pyelonephritis underwent CT
      and DW MRI examinations. Diffusion images were obtained by using a non-breath
      hold, single-shot echo-planar sequence with b values of 0, 600, and 1000 s/mm(2).
      Circular regions of interest were places on areas of nephritis, normal renal
      parenchyma, and renal abscesses as localized by CT and DW MRI images to obtain
      the ADC values of each of these regions. The ADC values of these three different
      tissue types were statistically compared using the one-way analysis of variance
      test for statistical significance. A P value <0.05 was considered to be
      statistically significant. RESULTS: For the diagnosis of pyelonephritis, DW MRI
      had a higher sensitivity of 95.3% as compared to that of non-contrast CT (66.7%)
      and contrast-enhanced CT (88.1%). Areas of nephritis had significantly lower ADC
      values (P < 0.001) than the normal renal cortical parenchyma. Also, renal
      abscesses had significantly lower ADC values (P < 0.001) than areas of nephritis.
      However, CT is more useful for the diagnosis of renal calculi and emphysematous
      pyelonephritis. CONCLUSION: ADC values derived from the diffusion sequence have
      significantly lower values in renal abscesses than in areas of nephritis.

PMID- 24443118
TI  - Analysis of fluorescence transients of DCMU-treated leaves of Triticum species to
      provide estimates of the densities of photosystem II reaction centres.
AB  - The fluorescence of the chlorophyll associated with photosystem II was studied in
      seedling and flag leaves of Triticum species. Seedling leaves of the diploid
      species T. urartu had higher values of t (the normalised area over the
      fluorescence induction curve of DCMU treated leaves) than those of the other
      species studied which included hexaploid T. aestivum. However this difference was
      not evident when leaves were grown in a low light intensity (40 umol quanta of
      photosynthetically active radiation m(-2) s(-1)). The smaller total number of
      chlorophyll molecules per photosystem II reaction centre (chl/RCII) in T. urartu
      (177) as compared with the other species (mean 234) was deduced from the observed
      differences in t. As a consequence of its lower chl/RCII, despite slightly lower
      chlorophyll content (mg m(-2)), T. urartu had a greater density of reaction
      centres than the other species (2880 cf 2230 nmol m(-2) of leaf). Consistent with
      the lower chl/RCII of T. urartu, it had a higher chlorophyll a/b ratio than the
      other genotypes. Seedling leaves of T. urartu had higher light saturated rates of
      photosynthesis than those of the other species, when grown at high light, a
      difference associated with reaction centre density.In flag leaves, when the
      complications due to variable development and senescence patterns were
      eliminated, t of the diploid species including T. urartu was lower than that of
      T. aestivum. The lower apparent chl/RCII of T. urartu arose partly because the
      molar extinction coefficient of the chlorophyll in the leaves of T. urartu was
      greater than in T. aestivum. However, the density of PS II reaction centres was
      slightly lower for the diploid species studied because their chlorophyll contents
      were lower than the hexaploids.The validity of the method for estimating chl/RCII
      from fluorescence transients is discussed. The possibility is considered that the
      difference in apparent chl/RCII of flag and seedling leaves of R. urartu as
      compared to the other five genotypes is a consequence of its different adaptive
      response to the spectral quality of the light. 

PMID- 24443117
TI  - Enhanced phase regression with Savitzky-Golay filtering for high-resolution BOLD
      fMRI.
AB  - Phase regression exploits the temporal evolution of phase in individual voxels to
      suppress blood oxygenation level dependent (BOLD) signal fluctuations caused by
      larger vessels and draining veins while preserving signal changes from
      microvascular effects. However, this process does not perform well when phase
      time series have low signal-to-noise ratios because of high levels of
      physiological noise. We demonstrate that Savitzky-Golay filters may be used to
      recover the underlying change in phase and completely restore the efficacy of
      phase regression. We do not make a priori assumptions regarding phase evolution
      and perform a data-driven exploration of parameter space to select the Savitzky
      Golay filter parameters that minimize temporal variance in each voxel after phase
      regression. This approach is shown to work well on data acquired with single-shot
      and multi-shot pulse sequences, and should therefore be useful for both human and
      animal gradient-echo fMRI at high spatial resolutions at high fields. The ability
      to improve the spatial specificity of BOLD activation may be especially
      advantageous for clinical applications of fMRI that rely upon the accuracy of
      individual subject's activation maps to assist with presurgical planning and
      clinical decision-making. Enhanced phase regression with Savitzky-Golay filtering
      may also find other uses in analyses of resting state functional connectivity.

PMID- 24443119
TI  - Pigment protein complexes and functional properties of tetratype resulting from
      crosses between CP1 and CP 2 less Chlamydomonas mutants.
AB  - A chlorophyll b-less mutant of Chlamydomonas reinhardtii (Pg 27) was isolated
      after UV irradiation of the wild type cells. This photosynthetically competent
      mutant totally lacks chlorophyll b and the CP2 chlorophyll-protein complex.
      However, SDS-PAGE, proteolytic digestions and immunodetections demonstrated that
      the 24-25 Kd apoproteins of the lacking CP2 complex are still present in
      thylakoids of the Pg27 mutant. It is concluded that this CP2-less mutant is
      affected in the biosynthesis pathway of chlorophyll b.This CP2-less mutant was
      crossed with a CP1-less mutant (Fl5) Fluorescence emission spectra and
      fluorescence inductions in the presence of DCMU were analysed in the resulting
      (cp 2 (-) , cp 1 (+) ), (cp 2 (+) , cp 1 (-) ), (cp 2 (+) , cp 1 (+) ), cp 2 (-)
      , cp 1 (-) )tetratype. Differences in PS 2 optical cross section and in the
      relative amplitude or localisation of fluorescence emission peaks fit well with a
      quadripartite model where PS1 and PS2 would each correspond to a reaction centre
      core complex (CP1 and CP2 respectively) associated to a light harvesting antenna
      (LHC1 and LHC2 respectively). The occurrence of energy transfers from PS1
      peripheral antenna to PS2 in the Fl 5 mutant shows that, in absence of CP1, at
      least a part of its associated PS1 light harvesting antenna migrates in the PS2
      containing appressed thylakoids. 

PMID- 24443120
TI  - Chlorophyll-protein and polypeptide composition of Mn-deficient sugar beet
      thylakoids.
AB  - The chlorophyll-protein and polypeptide composition of manganese deficient and
      control sugar beet thylakoids was examined using three different detergent
      electrophoresis systems. On a per chlorophyll basis, manganese deficiency reduced
      the amounts of CPa complex (separated by sodium dodecylsulfate (SDS)
      polyacrylamide gel electrophoresis), and CP 47 and CP 43 complexes (separated by
      octylglucoside/SDS-polyacrylamide gel electrophoresis) without decreasing the
      amounts of light harvesting complexes. Lithium dodecylsulfate/Triton X-100
      polyacrylamide gel electrophoresis showed that manganese deficiency decreased
      several thylakoid polypeptides, including a chlorophyll b containing 30
      kilodalton chlorophyll-protein complex, but did not decrease the amounts of 28
      and 29 kilodalton light-harvesting chlorophyll b-containing polypeptides. 

PMID- 24443121
TI  - Photosynthetic electron transfer and membrane energization in spheroplasts and
      membrane vesicles of the thermophilic cyanobacterium Synechoccus 6716.
AB  - The higher the incubation temperature, the higher the light intensity that
      membrane vesicles of the thermophilic cyanobacterium Synechococcus 6716 require
      for the saturation of O2-production. If membrane vesicles are incubated at
      temperatures at which intact cells are growing optimally, photosynthetic O2
      production and membrane energization decrease rapidly, suggesting that the
      thermophilic properties are rapidly lost. If membrane integrity is maintained
      (spheroplasts) the harmful effect of higher temperatures is much less. The
      effects of 2,5-dibromo-3-methyl-6-isopropyl-p-benzo-quinone (DBMIB), 5-chloro-3-t
      butyl-2'-chloro-4'-nitrosalicylanilide (S-13), 3-(3,4-dichlorophenyl)-1,1
      dimethylurea (DCMU) and N,N'-dicyclohexylcarbodiimide (DCCD) are the same as in
      chloroplasts, be it that DCCD acts as an electron transfer inhibitor at higher
      concentrations. The supposed alternative site of DCMU inhibition in cyanobacteria
      is rejected.Spheroplasts show a reversible energy-dependent fluorescence
      quenching of 9-amino-6-chloro-2-methoxyacridine (ACMA) caused by illumination.
      ATP hydrolysis only give rise to fluorescence quenching in membrane vesicles.
      Long incubation at higher temperatures reduces the fluorescence quenching of
      membrane vesicles and spheroplasts, the latter being more stable than the former.

PMID- 24443122
TI  - Estimation of the light distribution between photosystems I and II in intact
      wheat leaves by fluorescence and photoacoustic measurements.
AB  - Usisng intact leaves, the extent of the decrease in chlorophyll a fluorescenece
      caused by the addition of continuous 710 nm light superimposed on modulated (20
      Hz) 550 nm light was used to determine the distribution of this absorbed light
      between photosystems I (alpha) and II (beta). The Fo and Fm levels, which defined
      the total variable fluorescenece, were taken as equal to those obtained with
      excess 710 nm light and with saturating blue-green light, respectively.An
      analogous procedure was used with a photoacoustic detector, saturating white
      light defining a base line for oxygen yield, the levels with an without 710 nm
      light being used to define beta and alpha respectively.The two methods gave
      similar values for the distribution of light between the two photosystems for the
      experimental conditions used, beta averaging 0.55 for a range of Triticum
      genotypes and Brachypodium sylvaticum grown in high or low light. 

PMID- 24443123
TI  - A BASIC computer program for calculation of photosynthesis, stomatal conductance,
      and related parameters in an open gas exchange system.
AB  - Computer programs written in BASICA (IBM'S VERSION OF BASIC) language were
      developed for the calculation of the gas exchange parameters of CO2 assimilation,
      leaf conductance, stomatal conductance, residual conductance, intercellular CO2
      concentration, transpiration, water use efficiency and transpiration ratio in an
      open system. Formulas are discussed in both an algebraic and in a BASIC computer
      program form. Calculations based on mole fractions of CO2 and water vapor are
      explained and both molar and mass fluxes are included in the program output to
      facilitate comparisons with data from the literature. Corrections are made in the
      program to account for under-estimation of CO2 assimilation due to the increase
      in flow rates out of sample chambers caused by simultaneous transpiration. A
      sample output is included to illustrate the formatting capability of the program.

PMID- 24443124
TI  - Pigment organization and energy transfer in the green photosynthetic bacterium
      Chloroflexus aurantiacus : I. The cytoplasmic membrane.
AB  - We have studied the pigment arrangement in purified cytoplasmic membranes of the
      thermophilic green bacterium Chloroflexus aurantiacus. The membranes contain 30
      35 antenna bacteriochlorophyll a molecules per reaction center; these are
      organized in the B808-866 light-harvesting complex, together with carotenoids in
      a 2:1 molar ratio. Measurements of linear dichroism in a pressed polyacrylamide
      gel permitted the accurate determination of the orientation of the optical
      transition dipole moments with respect to the membrane plane. Combination of
      linear dichroism and low temperature fluorescence polarization data shows that
      the Qy transitions of the BChl 866 molecules all lie almost perfectly parallel to
      the membrane plane, but have no preferred orientation within the plane. The BChl
      808 Qy transitions make an average angle of about 44 degrees  with this plane.
      This demonstrates that there are clear structural differences between the B808
      866 complex of C. aurantiacus and the B800-850 complex of purple bacteria.
      Excitation energy transfer from carotenoid to BChl a proceeds with about 40%
      efficiency, while the efficiency of energy transfer from BChl 808 to BChl 866
      approaches 100%. From the minimal energy transfer rate between the two spectral
      forms of BChl a, obtained by analysis of low temperature fluorescence emission
      spectra, a maximal distance between BChl 808 and BChl 866 of 23 A was derived. 

PMID- 24443125
TI  - Photosynthesis research. Volume 7 (1985/1986) contents.

PMID- 24443129
TI  - ESR white paper on teleradiology: an update from the teleradiology subgroup.
AB  - BACKGROUND: Teleradiology services are increasingly integrated into the workflow
      of radiological departments in EU-member states. METHODS: The current
      technological possibilities and European political agenda are both opening the
      way for cross-border telemedicine services including teleradiology. RESULTS: This
      is bringing new opportunities for both users and providers of teleradiology
      services, which has led to the idea of producing an updated version of earlier
      ESR statements and communications on teleradiology. For this purpose the e-Health
      and Informatics subcommittee established a Teleradiology subgroup. CONCLUSION:
      This white paper proposes comprehensive best-practice guidelines for
      teleradiology usage, focussing on services within the European Union, as prepared
      by the members of the ESR teleradiology subgroup. MAIN MESSAGES: * Teleradiology
      describes the provision of radiology services remote from the site where the
      images are obtained. * Teleradiology should form part of and be integrated with
      the wide spectrum of radiology services, and not a separate tradable commodity *
      The quality of radiological reports and services delivered by teleradiology
      should not be less than those of local radiologists * International quality
      standards for teleradiology need to be established * Patients need to be fully
      informed when teleradiology is used.

PMID- 24443127
TI  - Dynamics of the exponential integrate-and-fire model with slow currents and
      adaptation.
AB  - In order to properly capture spike-frequency adaptation with a simplified point
      neuron model, we study approximations of Hodgkin-Huxley (HH) models including
      slow currents by exponential integrate-and-fire (EIF) models that incorporate the
      same types of currents. We optimize the parameters of the EIF models under the
      external drive consisting of AMPA-type conductance pulses using the current
      voltage curves and the van Rossum metric to best capture the subthreshold
      membrane potential, firing rate, and jump size of the slow current at the
      neuron's spike times. Our numerical simulations demonstrate that, in addition to
      these quantities, the approximate EIF-type models faithfully reproduce
      bifurcation properties of the HH neurons with slow currents, which include spike
      frequency adaptation, phase-response curves, critical exponents at the transition
      between a finite and infinite number of spikes with increasing constant external
      drive, and bifurcation diagrams of interspike intervals in time-periodically
      forced models. Dynamics of networks of HH neurons with slow currents can also be
      approximated by corresponding EIF-type networks, with the approximation being at
      least statistically accurate over a broad range of Poisson rates of the external
      drive. For the form of external drive resembling realistic, AMPA-like synaptic
      conductance response to incoming action potentials, the EIF model affords great
      savings of computation time as compared with the corresponding HH-type model. Our
      work shows that the EIF model with additional slow currents is well suited for
      use in large-scale, point-neuron models in which spike-frequency adaptation is
      important. 

PMID- 24443130
TI  - [Editorial].

PMID- 24443131
TI  - [Lid reconstruction: functional and aesthetic aspects].
AB  - There are numerous different procedures for eyelid reconstruction, one of them
      being the transfer of pedicled full eyelid flaps. With regard to the increasing
      demands of the patients the so-called sandwich techniques in most cases offer the
      chance to get the best functional and aesthetic result in a individual situation.
      Some of these techniques are presented here. 

PMID- 24443132
TI  - [Patient satisfaction after transverse blepharotomy (Wies procedure) in the
      management of senile entropion - a postoperative analysis].
AB  - BACKGROUND: Senile entropion is a common pathology of the aging lid. Chronic
      irritation of the conjunctiva and/or cornea is bothersome to the patients and may
      cause severe complications. Surgical intervention is typically required. We
      present data from a postoperative telephone interview of 38 patients undergoing
      43 entropion repairs, which were performed as transverse blepharotomy according
      to Wies in the modification of Collin. PATIENTS AND METHODS: In a retrospective
      study 43 surgeries were evaluated. Mean follow-up time was 34 (6-96) months. 8
      entropions were recurrencies, one surgery was performed after ectropion. Patient
      satisfaction, complications and symptoms after surgery and frequency of repeated
      surgery were evaluated by sending a questionnaire with subsequent telephone
      survey. RESULTS: The transverse blepharotomy was successful in 31 cases (91.2 %)
      as a primary surgical intervention. In recurrencies, a successful result was
      obtained in 8 lids (88.9 %). 4 lids underwent further surgical procedures: 2/43
      eyes developed another entropion (4.7 %), one exhibited overcorrection/ectropion
      and one developed a lid malposition which could not be exactly specified during
      telephone interview. 2 patients complained of newly appearing dry eye
      symptoms/foreign body sensation (4.7 %) and one each suffered from granuloma due
      to incompletely removed suture material and fistulation. CONCLUSION: Although
      being a historically "old" surgical technique to treat involutional entropion,
      horizontal blepharotomy according to Wies proved successful in the vast majority
      of our patients. The overall success rate in our series was 90.7 % and rose to
      91.2 % in cases of primary surgery. Even in recurrent disease, 88.9 % of
      surgeries resulted in sustained correction of the lid malposition.

PMID- 24443133
TI  - [Surgical treatment of festoons].
AB  - The well introduced surgical techniques of lower lid blepharoplasty can only
      repair aesthetic problems between the lid margin and the orbital rim. The
      neighbouring malar area is located outside the orbit and requires specialised
      procedures to reposition the sunken malar orbicularis muscle (festoon) and the
      malar fat pad. A small incision at the lateral canthus provides the access to
      combine three procedures: transconjunctival lower lid blepharoplasty, lateral
      canthoplasty and malar lift. 

PMID- 24443134
TI  - [Can an intrascleral implant and/or the combined cataract surgery improve the
      long-term outcome of viscocanalostomy in glaucoma?].
AB  - BACKGROUND: Beside the established methods in glaucoma surgery, several
      procedures have been developed in the recent past including viscocanalostomy as a
      non-penetrating surgery. The efficiency of a combination of this procedure with
      an intrascleral implant and/or with cataract surgery was examined in this
      retrospective study over a period to 60 months postoperatively. PATIENTS AND
      METHODS: 67 eyes from 49 patients with glaucoma were operated in two different
      operational groups. 39 eyes had a viscocanalostomy (Group "V"). 16 eyes in this
      group additionally got a T-Flux implant ("ViskoT"), 23 did not ("Visko"). A
      combined cataract extraction and viscocanalostomy was undertaken in 28 eyes
      (Group "VK"), 18 of which did not ("ViskoKa"), and 10 of which did receive a T
      flux implant ("ViskoKaT"). RESULTS: The mean preoperative intraocular pressure
      was 27.1 +/- 4.5 mmHg and went down to 17.4 +/- 2.9 mmHg postoperative up to the
      point of 60 months: there was a significant difference in the overall
      postoperative intraocular pressure in comparison to the preoperative intraocular
      pressure. There was, however, no significant effect to be found until after 5
      years on the postoperative intraocular pressure by cataract extractions and also
      not by the implantation of a T-Flux. However, significantly less medication was
      applied up to the postoperative point of 12 and 36 months in the group with
      cataract surgery (VK). This difference was lost in the course of time and was no
      longer detectable after 60 months. However, an overall rise in both medication
      and goniopuncture (31.3 %) of the Descemet using YAG laser was necessary in the
      course of time, in order to keep a constant level of the postoperative
      intraocular pressure. CONCLUSIONS: Viscocanalostomy represents a safe surgical
      antiglaucomatous method for improving the intraocular pressure. A respective
      clinical improvement could be observed during the follow-up period of up to 60
      months. The prognosis of intraocular pressure does not improve by the use of
      intrascleral implants and viscocanalostomy with simultaneous cataract surgery,
      however.

PMID- 24443135
TI  - [Surgical treatment of chronic macular oedema with a combination therapy].
AB  - BACKGROUND: The treatment of therapy-resistent chronic macular oedema remains a
      challenge. Therefore a combination therapy, consisting of medical, biological and
      mechanical components was assessed. METHODS: A surgical treatment was performed
      in 35 eyes (34 patients) with chronic and therapy-resistant macular oedema,
      resulting from diabetic maculopathy (n = 25), vitreoretinal traction (n = 7) or
      following a retinal venous occlusion (n = 3). An intravitreal injection of
      bevacizumab was given on the day before surgery, consisting of pars plana
      vitrectomy with ILM peeling with Brilliant Blue G (BBG), as well as an air
      tamponade combined with postoperative prone positioning. The visual function and
      the central retinal thickness were measured in follow-up. RESULTS: Functionally,
      the visual acuity could be stabilised to an average of 0.18 and macular oedema
      was reduced in most patients. Anatomically, a significant reduction in central
      macular thickness by 193 um (29 %), from 598 um to 405 um (p < 0.001), and a
      regression in the intraretinal cystoid changes were observed. No significant
      complications occurred, whereas in 6 patients additional consecutive treatment
      was necessary. CONCLUSION: A stabilisation of the visual acuity and an
      improvement in the structural retinal situation could be achieved by an elaborate
      combination therapy, based on a pharmacological, a biological and a mechanical
      approach. Long-term follow-up and consecutive supplementary treatments are
      necessary to ensure the functional stability.

PMID- 24443136
TI  - [Retinovascular findings in Susac's syndrome].
AB  - BACKGROUND: Susac syndrome is a vasculopathy affecting the central nervous
      system, retina and cochlea leading to the triad encephalopathy, branch retinal
      artery occlusions and hearing loss. To date, about 300 cases have been described
      in the literature. PATIENTS/METHODS: Three patients with confirmed Susac syndrome
      were evaluated for disease-specific retinal pathologies. In addition, the overall
      history of the disease is presented to put the ophthalmological pathology into
      context. RESULTS: All three cases showed a retinal occlusive microangiopathy with
      branch retinal artery occlusions. MRI imaging revealed snowball-like lesions of
      the corpus callosum in two of three cases. At the initial presentation not all
      criteria of the disease-specific triad encephalopathy, branch retinal artery
      occlusions, and hearing loss were fulfilled in the three patients. CONCLUSION:
      Interdisciplinary collaboration between neurologists, otorhinolaryngologists and
      ophthalmologists is mandatory to establish the diagnosis of the disease. The
      occurrence of the characteristic retinal pathology with small artery occlusions
      and a segmental vasculopathy should always lead to the differential diagnosis of
      Susac syndrome.

PMID- 24443137
TI  - [Eye and death].

PMID- 24443138
TI  - [Keratitis caused by herpes simplex and varicella zoster virus].

PMID- 24443139
TI  - Structural and antigenic stability of H5N1 hemagglutinin trimer upon release from
      polyanhydride nanoparticles.
AB  - Although H5N1 avian influenza has not yet acquired the capacity to readily infect
      humans, should it do so, this viral pathogen would present an increasing threat
      to the immunologically naive human population. Subunit vaccines based on the
      viral glycoprotein hemagglutinin (HA) can provide protective immunity against
      influenza. Polyanhydride nanoparticles have been shown to enhance efficacy of
      subunit vaccines, providing the dual advantages of adjuvanticity and sustained
      delivery resulting in enhanced protein stability and immunogenicity. In this
      work, a recombinant trimer of H5 (H53 ) was encapsulated and released from
      polyanhydride nanoparticles. Release kinetics of the encapsulated H53 were found
      to be dependent on polymer chemistry (i.e., hydrophobicity and molecular weight).
      Polyanhydride nanoparticles composed of sebacic anhydride and 1,6-bis(p
      carboxyphenoxy)hexane (CPH; that degrade into more acidic monomers) released
      structurally stable HA H53 , while H53 released from formulations composed of CPH
      and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) (that are amphiphilic and
      whose degradation products are less acidic) displayed unfolding of tertiary
      structure. However, the antigenicity of the H53 based on binding of a H5-specific
      monoclonal antibody was preserved upon release from all the formulations studied,
      demonstrating the value of polyanhydride nanoparticles as a viable platform for
      HA-based influenza vaccines.

PMID- 24443140
TI  - Reaction mechanism for the dual gold-catalyzed synthesis of dibenzopentalene: a
      DFT study.
AB  - A wide range of gold-catalyzed reactions based on a dual activation mechanism has
      recently been reported in the literature. Herein, we present a computational
      investigation of the mechanism for the formation of dibenzopentalenes from 1
      ethynyl-2-(phenylethynyl)benzene. Transition states have been found, which
      substantiate the dual activation mechanism previously published and furthermore
      point towards a continuous presence of two gold moieties throughout the
      mechanistic cycle, an observation of high importance for all reactions in the
      field of dual activation. The initial activation of the diyne has been shown to
      proceed via an intermolecular transfer of a cationic gold catalyst from the
      thermodynamically preferred geminal-sigma,pi-acetylide complex to the active non
      geminal analogue. Furthermore, the regioselectivity of a 5-endo versus a 6-endo
      cyclization has been addressed, and the 5-endo cyclization was found to be most
      favorable both thermodynamically and with regard to the activation barrier. 

PMID- 24443141
TI  - Microwave-assisted synthesis and evaluation of acylhydrazones as potential
      inhibitors of bovine glutathione peroxidase.
AB  - Glutathione peroxidases (GPx) were the first selenocysteine enzymes identified.
      They play critical roles in cellular defense to excessH(2)O(2) and lipid
      peroxides, with GPx1 contributing the most cellular activity. In the treatment of
      cancer, for example, in lymphomas and leukaemias, evidence has been accumulating
      that up-regulation of the GPx system may serve to protect cancer cells from
      oxidative stress caused by anticancer drugs. We hypothesize that small molecules
      which block GPx1 could help overcome acquired resistance to anticancer drugs by
      raising the level of oxidative stress in cancer cells. Our previous efforts
      identified an acylhydrazone as a lead structure for the inhibition of GPx1. Now
      we report the microwave-supported synthesis and inhibitory screening of a series
      of 78 analogs. The special conformational isomerism resulting of the
      acylhydrazone functionality was investigated by the analysis of distinct NMR data
      and crystal structures, indicating that conformers at the C(O)-N hydrazide bond
      are responsible for this phenomena. Though some of the analogs showed poor
      aqueous solubility and could not be tested in the enzyme assay, the combinatorial
      approach led to the identification of a closely related isomer of the lead
      compound with increased inhibitory activity: N'-[1-(4-hydroxyphenyl)ethylidene]-2
      (1H-imidazol-1-yl)acetohydrazide. This success supports the idea that novel GPx1
      inhibitors can be developed by drug-design methods and paves the way for a new
      class of GPx1 inhibitors.

PMID- 24443142
TI  - Sensitivity and specificity of presumptive tests for blood, saliva and semen.
AB  - PURPOSE: Despite their wide use, the limits of presumptive tests can be poorly
      understood. The aim of this study was to investigate the specificity and
      sensitivity of conventional, as well as innovative, presumptive tests for blood,
      semen and saliva. METHODS: We investigated Kastle-Meyer (KM) and leucomalachite
      green (LMG) tests for blood with regard to their sensitivity and specificity in
      the presence of oxidizing (hypochlorite) and anti-oxidizing (ascorbic acid)
      agents. The suitability and specificity of the red starch paper (RSP) test for
      saliva was assessed. Finally, the inhibitory effect of detergent on the acid
      phosphatase (AP) test for semen was investigated along with possible cross
      reactions to tea stains. RESULTS: Our results confirm previous findings of higher
      sensitivity and specificity of the KM test compared to LMG test for blood.
      Contrary to previous studies, no statistically significant difference was
      observed in the sensitivity of the tests between dry and wet stains. The novel
      RSP test was found to successfully detect saliva. We demonstrated that acid
      phosphatase (AP) testing for semen is possible on used RSP. A common multipurpose
      detergent had an inhibitory effect on AP tests. False positive results were
      obtained from tea stains. Testing different sorts of tea (black, green and herbal
      teas) revealed that only Camellia varieties produce positive result with the AP
      test, due to AP being present in the plants. CONCLUSIONS: From our results we
      conclude that specific knowledge of each test, including substances that may
      affect the test outcome, is imperative to ensure correct interpretation of
      presumptive test results.

PMID- 24443143
TI  - Low-dose CT in body-packers: delineation of body packs and radiation dose in a
      porcine model.
AB  - PURPOSE: To compare low-dose computed tomography (CT) with standard CT and
      conventional radiography (CR) regarding delineation of body packs and radiation
      dose. METHODS: Nine samples of illicit drugs including cocaine, heroin, and
      hashish were positioned in the rectum of a 121.5 kg pig cadaver. Each sample was
      scanned on a 64-row MDCT with 120 kV: one standard modulated pelvic protocol
      (STD), and without modulation at 80 mA (LD80), 30 mA (LD30), and 10 mA (LD10).
      Additionally, conventional abdominal anterior-posterior radiographs (77 kV and
      106 +/- 13 mA) were taken. Body pack characteristics (wrapping, content, shape)
      were rated independently by two radiologists and summarized to a delineation
      score from 0 to 9 with scores >=6 representing sufficient delineation. Mean
      delineation scores were calculated for CR and CT protocols. These were
      additionally differentiated for readings in soft tissue (S), lung (L), user
      defined, variable window settings (V), and in cumulative window evaluation
      including all the other window settings (SLV). Effective doses were calculated
      (mSv). RESULTS: The CR delineation score was insufficient (3.1 +/- 2.5; 2.4 +/-
      0.3 mSv). For CT, the SLV window setting performed best (p < 0.01). Its score
      significantly (p < 0.01) declined with decreasing effective radiation doses: STD
      (8.8 +/- 0.5; 10.6 mSv), LD80 (8.2 +/- 0.7; 2.6 mSv), LD30 (6.8 +/- 1.3; 1.0
      mSv), and LD10 (4.6 +/- 1.9; 0.3 mSv). Thus, LD30 was the protocol using the
      lowest but sufficient dose. Moreover, for LD30 further differentiation between
      the particular window settings resulted in scores of 6.4 +/- 1.3 (L), 6.3 +/- 1.2
      (V), and 3.1 +/- 1.0 (S). CONCLUSIONS: With appropriate window settings, low-dose
      CT at 30 mA allowed for sufficient body-pack delineation below the dose of CR,
      which itself performed insufficient.

PMID- 24443144
TI  - Normal fertility in male mice with deletion of beta-catenin gene in germ cells.
AB  - As a dual function protein, beta-catenin affects both cell adhesion and mediates
      canonical Wnt/beta-catenin cell signaling. beta-Catenin is prominently expressed
      in somatic Sertoli cells in the testis and postmeiotic germ cells, suggesting an
      additional role in spermatogenesis. It was reported previously that Cre/loxP
      mediated conditional inactivation of the beta-catenin gene (Ctnnb1) in male
      gonads using a protamine promoter-driven Cre transgene (Prm-cre) resulted in
      partial infertility, reduced sperm count, and abnormal spermatogenesis. In this
      report, we demonstrated that the conditional deletion of Ctnnb1 using a germ cell
      specific Cre transgene (Stra8-icre) had no effect on male fertility. We have
      shown that the Stra8-icre transgene was highly efficient in generating deletion
      in early pre-meiotic and post-meiotic cells. No differences in anatomical or
      histological presentation were found in the mutant testis, the production of
      viable sperm was similar, and no abnormalities in DNA sperm content were
      detected. We concluded that beta-catenin is fully dispensable in germ cells for
      spermatogenesis. The conflicting results from the earlier study may have been due
      to off-target expression of Prm-cre in testicular somatic cells. In future
      studies, the analysis of conditional mutants using several Cre-transgenes should
      be encouraged to reduce potential errors.

PMID- 24443145
TI  - Behavioral health and disasters: looking to the future.
AB  - Along with other manmade and natural disasters, oil spills produce profound and
      long-term impacts on the behavioral health of their survivors. Although previous
      and ongoing research has focused on producing evidence of the breadth and depth
      of these impacts, future efforts must begin to translate this evidence into
      developing and implementing policies, programs, and practices that effectively
      contribute to their prevention and mitigation. Drawing upon a conceptual
      framework of the behavioral health impacts of oil spills developed from data
      collected in the aftermath of the Exxon Valdez oil spill in 1989, this paper
      examines potential interventions designed to prevent or mitigate biopsychosocial,
      interpersonal, and intrapersonal impacts on behavioral health. Future efforts to
      translate behavioral health research into effective practice will require the
      formation and maintenance of academic-community partnerships for the purpose of
      building resilience to these impacts and providing targeted services to those
      most vulnerable to their long-term consequences. 

PMID- 24443146
TI  - Implementation of treatment guidelines for specialist mental health care.
AB  - BACKGROUND: A huge gap exists between the production of evidence and its take-up
      in clinical practice settings. To fill this gap, treatment guidelines, based on
      explicit assessments of the evidence base, are commonly employed in several
      fields of medicine, including schizophrenia and related psychotic disorders. It
      remains unclear, however, whether treatment guidelines have any impact on
      provider performance and patient outcomes, and how implementation should be
      conducted to maximise benefit. OBJECTIVES: The primary objective of this review
      was to examine the efficacy of guideline implementation strategies in improving
      process outcomes (performance of healthcare providers) and patient outcomes. We
      additionally explored which components of different guideline implementation
      strategies can influence process and patient outcomes. SEARCH METHODS: We
      searched the Cochrane Schizophrenia Group Register (March 2012), as well as
      references of included studies. SELECTION CRITERIA: Studies that examined
      schizophrenia-spectrum disorders to compare guideline implementation strategies
      with usual care or to assess the comparative efficacy of different guideline
      implementation strategies. DATA COLLECTION AND ANALYSIS: Review authors worked
      independently and in duplicate to critically appraise records from 882 studies;
      five individual studies met the inclusion criteria and were considered. As
      critical appraisal of the five included studies revealed substantial
      heterogeneity in terms of focus of the guideline, target of the intervention,
      implementation strategy and outcome measures, meta-analysis was carried out for
      antipsychotic co-prescribing only. MAIN RESULTS: Of the five included studies,
      practitioner impact was assessed in three. The five studies were generally at
      unclear risk of bias, and all evidence in the 'Summary of findings' table was
      graded by review authors as of very low quality. Meta-analysis of two studies
      revealed that a combination of several guideline dissemination and implementation
      strategies targeting healthcare professionals did not reduce antipsychotic co
      prescribing in schizophrenia outpatients (two studies, n = 1,082, risk ratio (RR)
      1.10, 95% confidence interval (CI) 0.99 to 1.23; corrected for cluster design: n
      = 310, RR 0.97, CI 0.75 to 1.25). One trial, which studied a nurse-led
      intervention aimed at promoting cardiovascular disease screening, found a
      significant effect in terms of the proportion of people receiving screening
      (blood pressure: n = 96, RR 0.07, 95% CI 0.02 to 0.28; cholesterol: n = 103, RR
      0.46, 95% CI 0.30 to 0.70; glucose: n = 103, RR 0.53, 95% CI 0.34 to 0.82; BMI: n
      = 99, RR 0.22, 95% CI 0.08 to 0.60; smoking status: n = 96, RR 0.28, 95% CI 0.12
      to 0.64; Framingham score: n = 110, RR 0.69, 95% CI 0.55 to 0.87), although in
      the analysis corrected for cluster design, the effect was statistically
      significant for blood pressure and cholesterol only (blood pressure, corrected
      for cluster design: n = 33, RR 0.10, 95% CI 0.01 to 0.74; cholesterol, corrected
      for cluster design: n = 35, RR 0.49, 95% CI 0.24 to 0.99; glucose, corrected for
      cluster design: n = 35, RR 0.58, 95% CI 0.28 to 1.21; BMI, corrected for cluster
      design: n = 34, RR 0.18, 95% CI 0.02 to 1.37; smoking status, corrected for
      cluster design: n = 32, RR 0.25, 95% CI 0.06 to 1.03; Framingham score, corrected
      for cluster design: n = 38, RR 0.71, 95% CI 0.48 to 1.03; very low quality).
      Regarding participant outcomes, one trial assessed the efficacy of a shared
      decision-making implementation strategy and found no impact in terms of
      psychopathology, satisfaction with care and drug attitude. Another single trial
      studied a multifaceted intervention to promote medication adherence and found no
      impact in terms of adherence rates. AUTHORS' CONCLUSIONS: With only five studies
      meeting inclusion criteria, and with limited low or very low quality usable
      information, it is not possible to arrive at definitive conclusions. The
      preliminary pattern of evidence suggests that, although small changes in
      psychiatric practice have been demonstrated, uncertainty remains in terms of
      clinically meaningful and sustainable effects of treatment guidelines on patient
      outcomes and how best to implement such guidelines for maximal benefit.

PMID- 24443147
TI  - Evidence-based identification of key beliefs explaining adult male circumcision
      motivation in Zimbabwe: targets for behavior change messaging.
AB  - Male circumcision (MC) reduces HIV acquisition among men, leading WHO/UNAIDS to
      recommend a goal to circumcise 80 % of men in high HIV prevalence countries.
      Significant investment to increase MC capacity in priority countries was made,
      yet only 5 % of the goal has been achieved in Zimbabwe. The integrated behavioral
      model (IBM) was used as a framework to investigate the factors affecting MC
      motivation among men in Zimbabwe. A survey instrument was designed based on
      elicitation study results, and administered to a representative household-based
      sample of 1,201 men aged 18-30 from two urban and two rural areas in Zimbabwe.
      Multiple regression analysis found all five IBM constructs significantly
      explained MC Intention. Nearly all beliefs underlying the IBM constructs were
      significantly correlated with MC Intention. Stepwise regression analysis of
      beliefs underlying each construct respectively found that 13 behavioral beliefs,
      5 normative beliefs, 4 descriptive norm beliefs, 6 efficacy beliefs, and 10
      control beliefs were significant in explaining MC Intention. A final stepwise
      regression of the five sets of significant IBM construct beliefs identified 14
      key beliefs that best explain Intention. Similar analyses were carried out with
      subgroups of men by urban-rural and age. Different sets of behavioral, normative,
      efficacy, and control beliefs were significant for each sub-group, suggesting
      communication messages need to be targeted to be most effective for sub-groups.
      Implications for the design of effective MC demand creation messages are
      discussed. This study demonstrates the application of theory-driven research to
      identify evidence-based targets for intervention messages to increase men's
      motivation to get circumcised and thereby improve demand for male circumcision.

PMID- 24443148
TI  - Subclonal variant calling with multiple samples and prior knowledge.
AB  - MOTIVATION: Targeted resequencing of cancer genes in large cohorts of patients is
      important to understand the biological and clinical consequences of mutations.
      Cancers are often clonally heterogeneous, and the detection of subclonal
      mutations is important from a diagnostic point of view, but presents strong
      statistical challenges. RESULTS: Here we present a novel statistical approach for
      calling mutations from large cohorts of deeply resequenced cancer genes. These
      data allow for precisely estimating local error profiles and enable detecting
      mutations with high sensitivity and specificity. Our probabilistic method
      incorporates knowledge about the distribution of variants in terms of a prior
      probability. We show that our algorithm has a high accuracy of calling cancer
      mutations and demonstrate that the detected clonal and subclonal variants have
      important prognostic consequences.

PMID- 24443149
TI  - Reply: To PMID 23996730.

PMID- 24443150
TI  - Trends in the teaching of analytically oriented psychiatry and psychotherapy.
AB  - For several years there has been ongoing discussion in the psychiatric literature
      of a presumed decline in the teaching ofpsychodynamic psychiatry in psychiatry
      residency training programs. Studies that have quantitatively focused on this
      subject are reviewed in this article. The author presents the results of a 1988
      1989 survey of directors of psychiatry residency training programs dealing with
      this subject and related questions. The findings of the study are analyzed and
      discussed. 

PMID- 24443151
TI  - General systems approaches in mental health administration : developing state
      university collaboration programs.
AB  - Developing state-university collaboration is the process of creating mechanisms
      to couple two systems for mutual benefit. Collaboration requires setting new
      organizational boundaries for both the state agency and the university and
      developing new patterns of information flow within and between the organizations.
      Each organization's homeostatic properties resist change; this resistance must be
      balanced by leaders' attention to the organization's developmental needs. The
      impact of collaboration increases tremendously after key thresholds of
      involvement are attained and a "critical mass" of faculty exerts a synergistic
      effect that shifts both the state agency and the university department to new
      functional states. 

PMID- 24443152
TI  - The development of the psychodynamic psychotherapist in supervision.
AB  - Supervision is a fundamental component of every clinical training program that
      teaches psychodynamic psychotherapy. However, the development of the
      psychodynamic therapist in supervision has been a relatively unexplored area.
      This article identifies nine areas of development of the psychodynamic
      psychotherapist in supervision, with an emphasis on the beginning trainee. The
      areas explored include aspects of the therapist's understanding of the patient
      and aspects of the therapist's use of himself or herself in the psychotherapy.
      Consideration of the trainee in each of these areas helps the supervisor better
      understand the specific strengths and weaknesses that the trainee brings to their
      work together and enables the supervisor to be more skillful in the difficult
      business of psychotherapy supervision. 

PMID- 24443153
TI  - Cognitive therapy training in u.s. Psychiatry residency programs.
AB  - Cognitive therapy (CT) is a relatively new mode of psychotherapy that is
      effective in the treatment of depression and other psychiatric disorders. The
      training directors of all U.S. general psychiatry residency programs were
      surveyed on the amount of time offered in teaching and supervision of CT and in
      other treatment modalities. Of the 127 responders, 91 % offer some classroom
      instruction in CT, 54% offer trainees supervised clinical experience, and 23%
      require such experience. The ranges of instructional time offered and number of
      patients treated per resident are broad. Thirty-seven percent of training
      directors consider graduating residents as qualified to practice CT, and 11%
      consider graduating residents as qualified to supervise others in CT. The authors
      conclude that little standardization exists in CT training, and they propose a
      minimum requirement. 

PMID- 24443154
TI  - Psychiatry residents' attitudes toward personal involvement in research.
AB  - This study explored residents' attitudes toward referring subjects to other
      residents' research studies and toward conducting their own research projects.
      With respect to referring subjects to other research investigations, the ease of
      the referral mechanism and potential benefits to patients were of prime
      importance to residents. With respect to participating in their own research
      projects, the learning opportunity provided by working with a faculty mentor was
      rated as the key motivator. A lack of available time and an abundance of other
      clinical demands discouraged research activity. Suggestions are offered for
      residency training programs that wish to increase resident interest and
      participation in research projects. 

PMID- 24443155
TI  - Comparison of child psychiatry residents' and training directors' perceptions of
      training for alcohol and substance abuse treatment.
AB  - Residents anddirectors of accredited child and adolescent psychiatry programs (N
      = 117) in the United States were surveyed (with a response rate of 89% and 76.9%,
      respectively) to determine the extent and adequacy of training offered for the
      identification and management of substance abuse disorders. Of the responders,
      24% of the residents indicated some exposure (>=1 hour) to an adolescent drug
      abuse treatment facility during their training. In contrast, 46% of the directors
      reported that their residents had such exposure. Residents consistently reported
      training to be less adequate than did directors. Only half of the residents
      reported that they felt adequately prepared to identify and initially manage a
      substance-abusing adolescent, whereas a somewhat higher percentage of the
      directors (59%) felt that their residents were adequately prepared for this
      function. 

PMID- 24443157
TI  - The sexuality curriculum in residency training.

PMID- 24443158
TI  - Attenuated serotonin transporter association between dorsal raphe and ventral
      striatum in major depression.
AB  - Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit
      alterations in several parts of the serotonergic neurotransmitter system, which
      are in turn involved in reward processing. However, previous investigations of
      the serotonin transporter (SERT) focused on regional differences with varying
      results depending on the clinical syndrome. Here, we aimed to describe the
      serotonergic system of MDD patients on a network level by evaluating SERT
      associations across brain regions. Twenty medication free patients with major
      depression and 20 healthy controls underwent positron emission tomography using
      the radioligand [(11) C]DASB. SERT binding potentials (BPND ) were quantified
      voxel-wise with the multilinear reference tissue model 2. In addition, SERT BPND
      was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain
      serotonergic neurotransmission. Whole-brain linear regression analysis was
      applied to evaluate the association of DRN SERT bindings to those in projection
      areas, which was followed by ANCOVA to assess differences in interregional
      relationships between patients and controls. Although both groups showed
      widespread positive correlations, group differences were restricted to decreased
      SERT associations between the DRN and the ventral striatum (right and left
      respectively: t=5.85, P<0.05 corrected and t=5.07, P<0.1 corrected) when
      comparing MDD patients (R(2)=0.11 and 0.24) to healthy subjects (R(2)=0.72 and
      0.66, P<0.01 and 0.05 corrected). Adjusting for age and sex did not change these
      findings. This study indicates a disturbed regulation between key regions
      involved in reward processing via the SERT. Our interregional approach highlights
      the importance of evaluating pathophysiological alterations on a network level to
      gain complementary information in addition to regional investigations.

PMID- 24443159
TI  - Comparative effectiveness of upfront treatment strategies in elderly women with
      ovarian cancer.
AB  - BACKGROUND: Observational studies comparing neoadjuvant chemotherapy to primary
      surgery for advanced-stage ovarian cancer are limited by strong selection bias.
      Multiple methods were used to control for confounding and selection bias to
      estimate the effect of primary treatment on survival for ovarian cancer. METHODS:
      The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used
      to identify women >= 65 years of age with stage II-IV epithelial ovarian cancer
      who survived > 6 months from the date of diagnosis and received treatment from
      1991 through 2007. Traditional regression analysis, propensity score-based
      analysis, and an instrumental variable analysis (IVA) using geographic location
      as an instrument were used to compare survival between neoadjuvant chemotherapy
      and primary surgery. RESULTS: A total of 9587 patients with stage II-IV ovarian
      cancer were identified. Use of primary surgery decreased from 63.2% in 1991 to
      49.5% by 2007, whereas primary chemotherapy increased from 19.7% in 1991 to 31.8%
      in 2007 (P < .0001). In the observational cohort survival (hazard ratio [HR] =
      1.27; 95% confidence interval [CI] = 1.19-1.35) was inferior for patients treated
      with neoadjuvant chemotherapy; both median survival (15.8 versus 28.8 months) and
      2-year survival (36% versus 56%) were lower in the neoadjuvant chemotherapy group
      compared to those who underwent surgery. In the IVA, primary treatment had
      minimal effect on overall survival (HR = 1.04; 95% CI = 0.67-1.60). The median
      survival for patients with a value of the instrument less than the median (24.0
      months, 95% CI = 23.0-25.0) and greater than or equal to median value of the IV
      (24.0 months, 95% CI = 23.0-26.0) were similar. CONCLUSIONS: Use of neoadjuvant
      therapy has increased over time. Survival with neoadjuvant chemotherapy did not
      differ significantly from primary surgery in elderly women in the United States.

PMID- 24443160
TI  - Non-ECG-gated myocardial perfusion MRI using continuous magnetization-driven
      radial sampling.
AB  - PURPOSE: Establishing a high-resolution non-ECG-gated first-pass perfusion (FPP)
      cardiac MRI technique may improve accessibility and diagnostic capability of FPP
      imaging. We propose a non-ECG-gated FPP imaging technique using continuous
      magnetization-driven golden-angle radial acquisition. The main purpose of this
      preliminary study is to evaluate whether, in the simple case of single-slice two
      dimensional imaging, adequate myocardial contrast can be obtained for accurate
      visualization of hypoperfused territories in the setting of myocardial ischemia.
      METHODS: A T1-weighted pulse sequence with continuous golden-angle radial
      sampling was developed for non-ECG-gated FPP imaging. A sliding-window scheme
      with no temporal acceleration was used to reconstruct 8 frames/s. Canines were
      imaged at 3T with and without coronary stenosis using the proposed scheme and a
      conventional magnetization-prepared ECG-gated FPP method. RESULTS: Our studies
      showed that the proposed non-ECG-gated method is capable of generating high
      resolution (1.7 * 1.7 * 6 mm(3) ) artifact-free FPP images of a single slice at
      high heart rates (92 +/- 21 beats/min), while matching the performance of
      conventional FPP imaging in terms of hypoperfused-to-normal myocardial contrast
      to-noise ratio (proposed: 5.18 +/- 0.70, conventional: 4.88 +/- 0.43).
      Furthermore, the detected perfusion defect areas were consistent with the
      conventional FPP images. CONCLUSION: Non-ECG-gated FPP imaging using optimized
      continuous golden-angle radial acquisition achieves desirable image quality
      (i.e., adequate myocardial contrast, high spatial resolution, and minimal
      artifacts) in the setting of ischemia.

PMID- 24443161
TI  - Distribution and function of TrkB receptors in the developing brain of the
      opossum Monodelphis domestica.
AB  - The expression, development pattern, spatiotemporal distribution, and function of
      TrkB receptors were investigated during the postnatal brain development of the
      opossum. Full-length TrkB receptor expression was detectable in the newborn
      opossum, whereas three different short forms that are expressed in the adult
      brain were almost undetectable in the newborn opossum brain. The highest level of
      full-length TrkB receptor expression was observed at P35, which corresponds to
      the time of eye opening. We found that in different brain structures, TrkB
      receptors were localized in various compartments of cells. The hypothalamus was
      distinguished by the presence of TrkB receptors not only in cell bodies but also
      in the neuropil. Double immunofluroscent staining for TrkB and a marker for the
      identification of the cell phenotype in several brain regions such as the
      olfactory bulb, hippocampus, thalamus, and cerebellum showed that unlike in
      eutherians, in the opossum, TrkB receptors were predominantly expressed in
      neurons. A lack of TrkB receptors in glial cells, particularly astrocytes and
      oligodendrocytes, provides evidence that TrkB receptors can play a functionally
      different role in marsupials than in eutherians. The effects of TrkB signaling on
      the development of cortical progenitor cells were examined in vitro using shRNAs.
      Blockade of the endogenous TrkB receptor expression induced a decrease in the
      number of progenitor cells proliferation, whereas the number of apoptotic
      progenitor cells increased. These changes were statistically significant but
      relatively small. In contrast, TrkB signaling was strongly involved in regulation
      of the cortical progenitor cell differentiation process.

PMID- 24443162
TI  - Quantitation of plastoquinone photoreduction in spinach chloroplasts.
AB  - The question of plastoquinone (PQ) concentration and its stoichiometry to
      photosystem I (PSI) and PSII in spinach chloroplasts is addressed here. The
      results from three different experimental approaches were compared. (a)
      Quantitation from the light-induced absorbance change at 263 nm (DeltaA263)
      yielded the following ratios (mol:mol); Chl:PQ=70:1, PQ:PSI=9:1 and
      PQ:PSIIalpha=7:1. The kinetics of PQ photoreduction were a monophasic but non
      exponential function of time. The deviation of the semilogarithmic plots from
      linearity reflects the cooperativity of several electron transport chains at the
      PQ pool level. (b) Estimates from the area over the fluorescence induction curve
      (Afl) tend to exaggerate the PQ pool size because of electron transfer via PSI to
      molecular oxygen (Mehler reaction) resulting in the apparent increase of the pool
      of electron acceptors. The reliability of the Afl method is increased
      substantially upon plastocyanin inhibition by KCN. (c) Quantitation of the number
      of electrons removed from PQH2 by PSI, either under far-red excitation or after
      the addition of DCMU to preilluminated chloroplasts, is complicated due to the
      competitive loss of electrons from PQH2 to molecular oxygen. The latter is
      biphasic reaction occurring with half-times of about 2 s (30-40% of PQH2) and of
      about 60 s (60-70% of PQH2). 

PMID- 24443163
TI  - Photosynthetic pathways in a midwestern rock outcrop succulent, Sedum
      nuttallianum Raf. (Crassulaceae).
AB  - Shoots of Sedum nuttallianum exhibited CAM(*) acid fluctuations in the field.
      These nocturnal acid accumulations persisted in the laboratory under well-watered
      and water-stressed conditions. Simultaneous measurements of transpiration,
      however, indicated daytime stomatal opening and nocturnal stomatal closure.
      Measurements of CO2 and H2O vapor exchange continuously for six days after
      watering substantiated these results in part: the majority of CO2 uptake occurred
      during the day early in the experiment; however, after several days without
      water, nighttime CO2 uptake was stimulated and eventually was greater than the
      drastically reduced daytime CO2 uptake. This nighttime uptake was never quite
      sufficient to account for all estimated increases in tissue acidity. Thus, a
      combination of CAM and CAM-cycling occurred early in the desiccation experiment.
      Evidence for CAM and a form of CAM-idling was found later in the experiment.
      Though nighttime CO2 uptake occurred and persisted after only one day without
      water, rates were too low to alter the tissue delta(13)C/(12)C value from a C3
      like number (-300/00). Thus, although CAM and CAM-idling may have survival value
      during extended droughts, shoots of S. nuttallianum apparently utilize the C3
      pathway to obtain most of their carbon. 

PMID- 24443164
TI  - Short-term CO2 exchange response to temperature, irradiance, and CO2
      concentration in strawberry.
AB  - Relative importance of short-term environmental interaction and preconditioning
      to CO2 exchange response was examined in Fragaria ananasa (strawberry, cv.
      Quinault). Tests included an orthogonal comparison of 15 to 60-min and 6 to 7-h
      exposures to different levels of temperature (16 to 32 degrees C),
      photosynthetically active radiation (PAR, 200 to 800 MUE m(2) s(-1)), and CO2
      (300 to 600 MUl/l) on successive days of study. Plants were otherwise maintained
      at 21 degrees C, 300 MUE m(2) s(-1) PAR and 300-360 MUl/l CO2 as standard
      conditions. Treatment was restricted to the mean interval of 14 h daily
      illumination and the first 3-4 days of each test week over a 12-week cultivation
      period. CO2 exchange rates were followed with each step-change in environmental
      level including ascending/descending temperature/PAR within a test period,
      initial response at standard conditions on successive days of testing, and
      measurement at reduced O2. Response generally supported prior concepts of leaf
      biochemical modeling in identifying CO2 fixation as the major site of
      environmental influence, while overall patterns of whole plant CO2 exchange
      suggested additional effects for combined environmental factors and
      preconditioning. These included a positive interaction between temperature and
      CO2 concentration on photosynthesis at high irradiance and a greater contribution
      by 'dark' respiration at lower PAR than previously indicated. The further
      importance of estimating whole plant CO2 exchange from repetitive tests and
      measurements was evidenced by a high correlation of response to prior treatment
      both during the daily test period and on consecutive days of testing. 

PMID- 24443165
TI  - The effects of chilling in the dark and in the light on photosynthesis of tomato:
      electron transfer reactions.
AB  - Exposure of tomato plants (Lycopersicon esculentum Mill. cv. Floramerica) to
      chilling temperatures in the dark for as little as 12 h resulted in a sizable
      inhibition in the rate of light- and CO2-saturated photosynthesis. However, when
      photosynthesis was measured at low light intensity, the inhibition disappeared
      and the quantum yield of CO2 reduction was diminished only slightly. Chilling the
      tomato plants under strong illumination caused an even more rapid and severe
      decline in the rate of light- and CO2-saturated photosynthesis, accompanied by a
      large decline in the quantum efficiency. Sizeable inhibition of photosystem II
      activity was observed only after dark exposures to low temperature of grater than
      16 h. No inhibition of photosystem I electron transfer capacity was observed even
      after 40 h of dark chilling. Chilling under high light resulted in a rapid
      decline in both photosystem I and photosystem II electron transfer capacity as
      well as in significant reaction center inactivation.Regardless of whether the
      chilling exposure was in the presence or absence of illumination and regardless
      of its duration, the electron transfer capacity of thylakoid membranes isolated
      from the treated plants was always in excess of that necessary to support light-
      and CO2-saturated photosynthesis. Thus, in neither case of chilling inhibition of
      photosynthesis does it appear that impaired electron transfer capacity represents
      a significant rate limitation to whole plant photosynthesis. 

PMID- 24443166
TI  - The inhibition of ribulose 1,5-bisphosphate carboxylase oxygenase by several 2
      carboxyhexitol 1- and 6-phosphates.
AB  - The condensation of D-fructose 6-phosphate or 1-phosphate with cyanide has been
      used to synthesize 2-carboxyhexitol 6-phosphates and 1-phosphates. The products
      have been characterized in terms of their action on ribulose bisphosphate
      carboxylase/oxygenase. The reaction of D-fructose 6-phosphate with cyanide is
      four times as fast (at 22 degrees C) at pH 7.5 than at pH 11.5 and the primary
      products of condensation are more easily isolated by anion exchange
      chromatography. Two minor chromatographic peaks (I and II) for diastereomeric 2
      carboxyhexitol 6-phosphates are isolated in addition to two major peaks, III and
      IV, which are lactones. The lactones are those of 2-C-carboxy-D-glucitol 6
      phosphate (CG6P) in peak III and 2-C-carboxy-D-mannitol 6-phosphate (CM6P) in
      peak IV, as established after dephosphorylation by the relative rates of
      oxidation by periodate and by gas chromatographic retention times of the
      acetates. Analogous methodology has been used to synthesize the diastereomeric 2
      carboxy-hexitol 1-phosphates (CG1P and CM1P) and their lactones from D-fructose 1
      phosphate. The four carboxylates inhibit ribulose bisphosphate
      carboxylase/oxygenase from spinach or Pseudomonas oxalaticus in the following
      decreasing order of potency: CG6P, CM6P, CG1P, CM1P. The inhibition pattern
      suggests that the binding of the 5-phosphate moiety of the intermediate in the
      reaction catalyzed by ribulose bisphosphate carboxylase/oxygenase may be stronger
      by an order of magnitude than the binding of the 1-phosphate group. 

PMID- 24443167
TI  - Participation of plastoquinone, cytochrome c 553 and ferrodoxin-NADP (+) oxido
      reductase in both photosynthesis and respiration in Spirulina maxima.
AB  - Dark and light oxidation of NADPH was measured in Spirulina maxima thylakoid
      membranes. The dark reaction was more cyanide sensitive than the light reaction.
      In light, 83% of the electrons from NADPH produced H2O2 on reducing oxygen,
      whereas in the dark this number was only 36%. These results are explained by
      assuming the presence of an electron transport segment common to the
      photosynthetic and the respiratory chains, so that electrons flowing through the
      cyanide sensitive oxidase in the dark are diverted to the photosytem (PS) I
      reaction center (P700). In addition, cytochrome (cyt) c 553 was found to be an
      electron donor for both cyt oxidase and P700. Half maximum reduction rates were
      obtained with 7 MUM cyt c 553. The intrathylakoidal concentration of cyt c 553
      was determined to be 83 MUM. About 60% of the respiratory NADPH oxidation
      activity was lost by extracting the membranes with pentane and was restored by
      adding plastoquinone (the main photosythetic quinone). NADPH oxidation activity
      was also inhibited upon washing the membranes with a low salt buffer. This
      activity was restored by adding partially purified ferredoxin-NADP(+) oxido
      reductase (FNR). A model for the electron transport in thylakoids, in which cyt c
      553, plastoquinone and FNR participate in both photosynthesis and respiration is
      proposed. 

PMID- 24443168
TI  - Characterization of the binding of valinomycin to bacteriorhodopsin.
AB  - Circular dichroism spectroscopy has been used to investigate the binding of
      valinomycin to bacteriorhodopsin in purple membrane suspensions. Addition of
      valinomycin to purple membrane suspensions obtained from Halobacterium halobium
      causes the circular dichroism spectrum to shift from an aggregate spectrum to one
      resembling a monomer spectrum, indicating a loss of chromophore-chromophore
      interactions. By observing the spectral change upon titration of valinomycin, an
      apparent dissociation constant of 30-40 MUM for valinomycin binding was
      determined. Kinetics of dark adaptation for valinomycin-treated purple membrane
      are comparable to those for monomeric bacteriorhodopsin. Centrifugation studies
      demonstrate that valinomycin-treated purple membrane sediments the same as
      untreated purple membrane suspensions. These results are consistent with a model
      in which valinomycin binds specifically to bacteriorhodopsin without disrupting
      the purple membrane fragments. 

PMID- 24443169
TI  - Species specific chlorophyll a fluorescence-temperature profile at high
      temperatures in the leaves.
AB  - Chlorophyll a (Chl a) fluorescence-temperature profile in the region of 20-80
      degrees C was recorded for fourteen different plant species. In all the species
      studied, there was a rise in the fluorescence intensity in the region of 45-50
      degrees C and around 55 degrees C the fluorescence intensity started to decline.
      In four of the species (Acacia melanoxylon, Ervatamia montana, Eucalyptus
      tertecornius and Azardicta indica) tested, there was a secondary rise in the
      fluorescence intensity around 65-70 degrees C whereas in all other species a
      sharp decline in the fluorescence intensity was observed at this point. These
      changes in the fluorescence intensity at high temperatures (65-70 degrees C)
      appear to be species specific and cannot be explained either in terms of changes
      in the stoichiometry between the two photosystems or in terms of Chl a
      fluorescence emission from photosystem I (PS I) at higher temperatures. This
      conclusion is supported by following observations: (1) there was no definite
      correlation between the Chl a/Chl b ratio and the pattern of fluorescence
      temperature profile at high temperatures; (2) the sun and shade plants of the
      same species had a similar pattern of fluorescence-temperature profile; and (3)
      preferential excitation of PS I did not alter the fluorescence-temperature
      profile. 

PMID- 24443170
TI  - End-of-Life Dreams and Visions: A Qualitative Perspective From Hospice Patients.
AB  - End-of-life dreams and visions (ELDVs) are well documented throughout history and
      across cultures with impact on the dying person and their loved ones having
      profound meaning. Published studies on ELDVs are primarily based on surveys or
      interviews with clinicians or families of dead persons. This study uniquely
      examined patient dreams and visions from their personal perspective. This article
      reports the qualitative findings from dreams and visions of 63 hospice patients.
      Inductive content analysis was used to examine the content and subjective
      significance of ELDVs. Six categories emerged: comforting presence, preparing to
      go, watching or engaging with the deceased, loved ones waiting, distressing
      experiences, and unfinished business.

PMID- 24443171
TI  - Imaging in Transcatheter Aortic Valve Replacement (TAVR): role of the
      radiologist.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a novel technique
      developed in the last decade to treat severe aortic stenosis in patients who are
      non-surgical candidates because of multiple comorbidities. METHODS: Since the
      technique is performed using a transvascular approach, pre-procedural assessment
      of the aortic valve apparatus, ascending aorta and vascular access is of
      paramount importance for both appropriate patient selection and correct device
      selection. This assessment is performed by a multi-disciplinary team with
      radiology being an integral and important part. RESULTS: Among imaging
      modalities, there is growing scientific evidence supporting the crucial role of
      MDCT in the assessment of the aortic valve apparatus, suitability of the
      iliofemoral or alternative pathway, and determination of appropriate coaxial
      angles. MDCT also plays an important role in post-procedure imaging in the
      assessment of valve integrity and position. CONCLUSION: This review outlines the
      principal aspects of TAVR, the multidisciplinary approach and utilisation of
      different imaging modalities, as well as a step-by-step approach to MDCT
      acquisition protocols, reconstruction techniques, pre-procedure measurements and
      post-procedure assessment. TEACHING POINTS: * TAVR is a new technique to treat
      severe aortic stenosis in high-risk and nonsurgical candidates. * MDCT assessment
      of the aortic annulus is important for appropriate patient and device selection.
      * Multidisciplinary approach is required for patient selection, procedure
      planning and performance. * MDCT is required for assessment of the aortic root,
      iliofemoral or alternative vascular pathway.

PMID- 24443172
TI  - Peripherally and axially carboxylic acid substituted subphthalocyanines for dye
      sensitized solar cells.
AB  - A series of subphthalocyanines (SubPcs) bearing a carboxylic acid group either at
      the peripheral or axial position have been designed and synthesized to
      investigate the influence of the COOH group positions on the dye-sensitized solar
      cell (DSSC) performance. The DSSC devices based on SubPcs with axially
      substituted carboxylic acid groups showed low photovoltaic performance, whereas
      peripherally substituted one exhibited higher power conversion efficiency owing
      to improved injection from LUMO of SubPcs to the TiO2 conduction band. 

PMID- 24443173
TI  - Recent progress on fluorous synthesis of biologically interesting compounds.
AB  - This article highlights research papers published in 2011 and 2012 on fluorous
      linker-assisted synthesis of biologically interesting small molecules and
      biomolecules. 

PMID- 24443174
TI  - Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose
      CT: final results after a 5-year screening programme.
AB  - BACKGROUND: We present the final results of the effect of lung cancer screening
      with low-dose CT on the smoking habits of participants in a 5-year screening
      trial. METHODS: The Danish Lung Cancer Screening Trial (DLCST) was a 5-year
      screening trial that enrolled 4104 subjects; 2052 were randomised to annual low
      dose CT (CT group) and 2052 received no intervention (control group).
      Participants were current and ex-smokers (>=4 weeks abstinence from smoking) with
      a tobacco consumption of >=20 pack years. Smoking habits were determined
      annually. Missing values for smoking status at the final screening round were
      handled using two different models. RESULTS: There were no statistically
      significant differences in annual smoking status between the CT group and control
      group. Overall the ex-smoker rates (CT + control group) significantly increased
      from 24% (baseline) to 37% at year 5 of screening (p<0.001). The annual point
      prevalence quit rate increased from 11% to 24% during the five screening rounds;
      the ex-smokers' relapse rate remained stable, around 11%, across the same period.
      CONCLUSIONS: Screening with low-dose CT had no extra effect on smoking status
      compared with the control group, but overall the screening programme probably
      promoted smoking cessation. CLINICAL TRIAL REGISTRATION: The DLCST is registered
      in Clinical Trials.gov Protocol Registration System (identification no.
      NCT00496977).

PMID- 24443175
TI  - Acute bilateral parotitis occurring during venlafaxine titration in an adolescent
      female with major depression.
AB  - Parotitis is a fairly uncommon adverse drug reaction of psychopharmacological
      treatment. Here, we report on an acute bilateral parotitis, which was associated
      with titration of venlafaxine in a 20-year-old female suffering from a severe
      depressive episode. The parotitis recovered quickly with oral penicillin and was
      most likely caused by bacteria assumed to spread from oral flora into Stensen's
      duct as a complication of pronounced venlafaxine-induced xerostomia. 

PMID- 24443176
TI  - Genomic organization and identification of promoter regions for the BDNF gene in
      the pond turtle Trachemys scripta elegans.
AB  - Brain-derived neurotrophic factor (BDNF) is an important regulator of neuronal
      development and synaptic function. The BDNF gene undergoes significant activity
      dependent regulation during learning. Here, we identified the BDNF promoter
      regions, transcription start sites, and potential regulatory sequences for BDNF
      exons I-III that may contribute to activity-dependent gene and protein expression
      in the pond turtle Trachemys scripta elegans (tBDNF). By using transfection of
      BDNF promoter/luciferase plasmid constructs into human neuroblastoma SHSY5Y cells
      and mouse embryonic fibroblast NIH3T3 cells, we identified the basal regulatory
      activity of promoter sequences located upstream of each tBDNF exon, designated as
      pBDNFI-III. Further, through chromatin immunoprecipitation (ChIP) assays, we
      detected CREB binding directly to exon I and exon III promoters, while BHLHB2,
      but not CREB, binds within the exon II promoter. Elucidation of the promoter
      regions and regulatory protein binding sites in the tBDNF gene is essential for
      understanding the regulatory mechanisms that control tBDNF gene expression. 

PMID- 24443177
TI  - Neural progenitor cells from human induced pluripotent stem cells generated less
      autogenous immune response.
AB  - The breakthrough development of induced pluripotent stem cells (iPSCs) raises the
      prospect of patient-specific treatment for many diseases through the replacement
      of affected cells. However, whether iPSC-derived functional cell lineages
      generate a deleterious immune response upon auto-transplantation remains unclear.
      In this study, we differentiated five human iPSC lines from skin fibroblasts and
      urine cells into neural progenitor cells (NPCs) and analyzed their
      immunogenicity. Through co-culture with autogenous peripheral blood mononuclear
      cells (PBMCs), we showed that both somatic cells and iPSC-derived NPCs do not
      stimulate significant autogenous PBMC proliferation. However, a significant
      immune reaction was detected when these cells were co-cultured with allogenous
      PBMCs. Furthermore, no significant expression of perforin or granzyme B was
      detected following stimulation of autogenous immune effector cells (CD3(+)CD8(-)
      T cells, CD3(+)CD8(+) T cells or CD3(-)CD56(+) NK cells) by NPCs in both PBMC and
      T cell co-culture systems. These results suggest that human iPSC-derived NPCs may
      not initiate an immune response in autogenous transplants, and thus set a base
      for further preclinical evaluation of human iPSCs. 

PMID- 24443178
TI  - Tissue engineered esophagus by copper--small intestinal submucosa graft for
      esophageal repair in a canine model.
AB  - Acellular porcine small intestinal submucosa (SIS) has been used for
      esophagoplasty with success in a canine model. However, it did not lead to
      complete epithelialization. For better reconstruction, a cellular component is
      required. Moreover, promotion of angiogenesis with copper has been widely
      recognized by basic research as well as clinical studies. In this study, we have
      evaluated the feasibility and effectiveness of combined Cu and SIS (SIS-Cu patch)
      for the esophageal repair using a canine model. Eighteen male beagle dogs were
      subjected to surgical resection to produce cervical esophageal defects (5 cm in
      length, 180 degrees  in range). SIS with Cu (5 or 25 MUmol L(-1) copper) or
      without Cu was patched on the esophageal defects. Barium esophagram and histology
      exam were carried out to evaluate the effectiveness of the therapy. As shown, the
      SIS-Cu graft promoted re-epithelialization, re-vascularization and muscular
      regeneration. SIS-Cu patch is more effective than SIS alone for esophageal
      repair, and the SIS+25 MUmol L(-1) Cu group demonstrated additional advantages
      over the SIS+5 MUmol L(-1) Cu. 

PMID- 24443179
TI  - Microenvironment-induced myofibroblast-like conversion of engrafted
      keratinocytes.
AB  - Myofibroblasts, recognized classically by alpha-smooth muscle actin (alpha-SMA)
      expression, play a key role in the wound-healing process, promoting wound closure
      and matrix deposition. Although a body of evidence shows that keratinocytes
      explanted onto a wound bed promote closure of a skin injury, the underlying
      mechanisms are not well understood. The basal layer of epidermis is rich in
      undifferentiated keratinocytes (UKs). We showed that UKs injected into
      granulation tissue could switch into alpha-SMA positive cells, and accelerate the
      rate of skin wound healing. In addition, when the epidermis sheets isolated from
      foreskin cover up the wound bed or are induced in vitro, keratinocytes located at
      the basal layers or adjacent sites were observed to convert into myofibroblast
      like cells. Thus, UKs have a potential for myofibroblastic transition, which
      provides a novel mechanism by which keratinocyte explants accelerate skin wound
      healing. 

PMID- 24443180
TI  - Transposon-dependent induction of Vincent van Gogh's sunflowers: exceptions
      revealed.
AB  - The radiate sunflower inflorescence is composed by zygomorphic ray flowers and
      actinomorphic disk flowers. Studies performed on mutants identify HaCYC2c, a
      CYCLOIDEA (CYC)-like gene, as one of the key players controlling flower symmetry
      in sunflower. turf and tub mutants are characterized by a shift from zygomorphic
      to actinomorphic ray flowers, caused by insertion of transposable elements (TEs)
      in HaCYC2c gene. In dbl or Chry mutants, an insertion upstream the coding region
      of HaCYC2c causes the ectopic expression of the gene and the shift from
      actinomorphic to zygomorphic disk flowers. We focused on Chry2 mutant: a 1034 bp
      insertion placed 558 bp before the start codon of HaCYC2c was identified. The
      insertion is a truncated version of a CACTA TE. Unexpectedly, phenotypic and
      genetic co-segregation analysis in F2 and F3 progenies derived from the crosses
      Chry2 * turf and turf * Chry2 demonstrated that CACTA insertion is not always
      sufficient to alter the expression of HaCYC2c gene and generate Chry2 phenotype.
      F3 plants homozygous for the CACTA insertion displayed either HaCYC2c
      transcription pattern identical to wild-type plants or a normal heterogamous
      inflorescence. Stated these results, we conclude that a much more complex
      regulatory system stays behind the Chry2 phenotype.

PMID- 24443182
TI  - Intensity and sulci landmark combined brain atlas construction for Chinese
      pediatric population.
AB  - Constructing an atlas from a population of brain images is of vital importance to
      medical image analysis. Especially in neuroscience study, creating a brain atlas
      is useful for intra- and inter-population comparison. Research on brain atlas
      construction has attracted great attention in recent years, but the research on
      pediatric population is still limited, mainly due to the limited availability and
      the relatively low quality of pediatric magnetic resonance brain images. This
      article is targeted at creating a high quality representative brain atlas for
      Chinese pediatric population. To achieve this goal, we have designed a set of
      preprocessing procedures to improve the image quality and developed an intensity
      and sulci landmark combined groupwise registration method to align the population
      of images for atlas construction. As demonstrated in experiments, the newly
      constructed atlas can better represent the size and shape of brains of Chinese
      pediatric population, and show better performance in Chinese pediatric brain
      image analysis compared with other standard atlases.

PMID- 24443183
TI  - Surface chemistry modulates osteoblasts sensitivity to low fluid shear stress.
AB  - Low fluid shear stress (FSS) is the mechanical environment encountered by
      osteoblasts in implanted bones or native bones of bed rest patients. High
      sensitivity of osteoblasts to low FSS is beneficial to osteogenesis. We
      hypothesize that this sensitivity might be regulated by chemical microenvironment
      provided by scaffolds. To confirm this hypothesis, self-assembled monolayers
      (SAMs) were used to provide various surface chemistries including OH, CH3 , and
      NH2 while parallel-plate fluid flow system produced low FSS (5 dynes/cm(2) ).
      Alterations in S-phase cell fraction, alkaline phosphatase activity, fibronectin
      (Fn), and collagen type I (COL I) secretion compared to those without FSS
      exposure were detected to characterize the sensitivity. Osteoblasts on OH and CH3
      SAMs demonstrated obvious sensitivity while on NH2 SAMs negligible sensitivity
      was observed. Examination of the cell aspect ratio, orientation, and focal
      adhesions before and after FSS exposure indicates that the full spreading and
      robust focal adhesions on NH2 SAMs should be responsible for the negligible
      sensitivity through increasing the cell tolerance to low FSS. Despite the higher
      sensitivity, the Fn and COL I depositions on both OH and CH3 SAMs after FSS
      exposure were still less than on NH2 SAMs without FSS exposure. These results
      suggest that elaborate design of surface chemical compositions is essential for
      orchestration of surface chemistry with low FSS to realize both high sensitivity
      and high matrix secretion, facilitating the formation of functional bone tissues
      in implanted bone.

PMID- 24443184
TI  - Heart fields: spatial polarity and temporal dynamics.
AB  - In chick and mouse, heart fields undergo dynamic morphological spatiotemporal
      changes during heart tube formation. Here, the dynamic change in spatial polarity
      of such fields is discussed and a new perspective on the heart fields is
      proposed. The heart progenitor cells delaminate through the primitive streak and
      migrate in a semicircular trajectory craniolaterally forming the bilateral heart
      fields as part of the splanchnic mesoderm. They switch their polarity from
      anteroposterior to mediolateral. The anterior intestinal portal posterior descent
      inverts the newly formed heart field mediolateral polarity into lateromedial by
      125 degrees  bending. The heart fields revert back to their original
      anteroposterior polarity and fuse at the midline forming a semi heart tube by
      completing their half circle movement. Several names and roles were assigned to
      different portions of the heart fields: posterior versus anterior, first versus
      second, and primary versus secondary heart field. The posterior and anterior
      heart fields define basically physical fields that form the inflow-outflow axis
      of the heart tube. The first and second heart fields are, in contrast, temporal
      fields of differentiating cardiomyocytes expressing myosin light chain 2a and
      undifferentiated and proliferating precardiac mesoderm expressing Isl1 gene,
      respectively. The two markers present a complementary pattern and are expressed
      transiently in all myocardial lineages. Thus, Isl1 is not restricted to a portion
      of the heart field or one of the two heart lineages as has been often assumed.

PMID- 24443185
TI  - Size of the anterior fontanelle: three-dimensional measurement of a key trait in
      human evolution.
AB  - The anterior fontanelle (AF) is an integral element of the developing human
      infant craniofacial system. Consideration of the AF is crucial for assessing
      craniofacial growth, as altered development of this feature may indicate abnormal
      growth. Moreover, prolonged patency of the AF may represent a derived hominin
      feature. The AF is regarded as essential for fetal head molding during birth in
      humans, with deformation of the head during birth often necessary for successful
      delivery. However, the function of a patent AF among fossil hominins is unclear.
      Because the AF represents an important structure in both a clinical and
      evolutionary context, techniques for estimating the size of the AF must be
      accurate and reproducible. Therefore, we have developed a novel method for
      assessing surface area of the AF with the goal of creating a more accurate
      measure of this feature. In this study, we test the accuracy and repeatability of
      a novel three-dimensional (3D) method for assessing the size of the AF in human
      infants and compare the results obtained for surface area of the AF using the
      conventional and 3D methods.

PMID- 24443186
TI  - The inferior olive of the C57BL/6J mouse: a chemoarchitectonic study.
AB  - We have used the histochemical and immunohistochemical staining methods and maps
      of gene expression to analyze the structure of the inferior olive of the C57BL
      mouse. As in other mammals, the inferior olive of the C57BL mouse contains three
      major nuclei, the medial nucleus, the principal nucleus, and the dorsal nucleus.
      The medial nucleus can be divided into a rostral medial nucleus and a more
      complex caudal part, which is formed by subnuclei C, B, A, the cap of Kooy, and
      the beta subnucleus. The principal nucleus includes the major principal nucleus
      and the arcuate subnucleus. Most of the inferior olive neurons are small to
      medium size, the smallest of which are found in the arcuate subnucleus. Calbindin
      and the vesicular glutamate transporter 2 gene are expressed in nearly all
      inferior olive neurons, but acetylcholinesterase, glutamate decarboxylase 1 gene,
      cocaine- and amphetamine-regulated transcript protein prepropeptide gene, galanin
      gene, and calretinin are selectively expressed within different subnuclei. These
      findings are consistent with a pattern of extensive functional differentiation
      among the neuron groups of the inferior olive.

PMID- 24443188
TI  - Mechanistic insight into peroxo-shunt formation of biomimetic models for compound
      II, their reactivity toward organic substrates, and the influence of N
      methylimidazole axial ligation.
AB  - High-valent iron-oxo species have been invoked as reactive intermediates in
      catalytic cycles of heme and nonheme enzymes. The studies presented herein are
      devoted to the formation of compound II model complexes, with the application of
      a water soluble (TMPS)Fe(III)(OH) porphyrin ([meso-tetrakis(2,4,6-trimethyl-3
      sulfonatophenyl)porphinato]iron(III) hydroxide) and hydrogen peroxide as oxidant,
      and their reactivity toward selected organic substrates. The kinetics of the
      reaction of H2O2 with (TMPS)Fe(III)(OH) was studied as a function of temperature
      and pressure. The negative values of the activation entropy and activation volume
      for the formation of (TMPS)Fe(IV)=O(OH) point to the overall associative nature
      of the process. A pH-dependence study on the formation of (TMPS)Fe(IV)=O(OH)
      revealed a very high reactivity of OOH(-) toward (TMPS)Fe(III)(OH) in comparison
      to H2O2. The influence of N-methylimidazole (N-MeIm) ligation on both the
      formation of iron(IV)-oxo species and their oxidising properties in the reactions
      with 4-methoxybenzyl alcohol or 4-methoxybenzaldehyde, was investigated in
      detail. Combined experimental and theoretical studies revealed that among the
      studied complexes, (TMPS)Fe(III)(H2O)(N-MeIm) is highly reactive toward H2O2 to
      form the iron(IV)-oxo species, (TMPS)Fe(IV)=O(N-MeIm). The latter species can
      also be formed in the reaction of (TMPS)Fe(III)(N-MeIm)2 with H2O2 or in the
      direct reaction of (TMPS)Fe(IV)=O(OH) with N-MeIm. Interestingly, the kinetic
      studies involving substrate oxidation by (TMPS)Fe(IV)=O(OH) and (TMPS)Fe(IV)=O(N
      MeIm) do not display a pronounced effect of the N-MeIm axial ligand on the
      reactivity of the compound II mimic in comparison to the OH(-) substituted
      analogue. Similarly, DFT computations revealed that the presence of an axial
      ligand (OH(-) or N-MeIm) in the trans position to the oxo group in the iron(IV)
      oxo species does not significantly affect the activation barriers calculated for
      C-H dehydrogenation of the selected organic substrates.

PMID- 24443189
TI  - A time of transition.

PMID- 24443190
TI  - Teaching and learning psychiatry.
AB  - This article reviews the teaching-learning process in psychiatry. It describes
      eight attributes of a successful teacher, suggests ways that psychiatrists may
      improve their teaching skills, and delineates four stages (exposure,
      incorporation, integration, and mastery) of the learning process that have
      implications for how and what we teach. Methods to evaluate teaching rigorously
      so that it can be academically rewarded are described. At a time when the place
      of the psychiatric teacher in the academic medical center is precarious and often
      discouraging, the author discusses sources of support from students, fellow
      faculty, and national colleagues that can help sustain teaching in, and teachers
      of, psychiatry. 

PMID- 24443191
TI  - Order and chaos : subspecialization and american psychiatry.
AB  - Psychiatrie subspecialties have emerged rapidly during the past decade. This
      article discusses significant influences in nonpsychiatric medicine and
      psychiatry that led to these developments. The process f or new subspecialty
      recognition, certification, and accreditation is outlined. The status of the
      major psychiatric subspecialties is reviewed. The impact of the changing
      recruitment into psychiatry is discussed for subspecialization, the psychiatric
      generalist, and psychiatric educational resources. 

PMID- 24443192
TI  - Learning priorities of staff, residents, and students for a third-year
      psychiatric clerkship.
AB  - Psychiatric clerkships combine classroom instruction with patient care. The
      different learning experiences in those two settings prompted the authors to
      survey 86 third-year medical student clerks, 44 staff psychiatrists, and 15 PGY-2
      psychiatric residents about the importance of 31 skill and knowledge areas as
      learning goals for clerks. All groups of respondents included the following five
      items (16.2%) among the most important: performing a mental status examination,
      becoming comfortable with psychiatric patients, evaluating suicidally, developing
      interview skills, and suspecting drug and alcohol problems. The importance placed
      by staff on aspects of the doctor-patient relationship was not apparent to
      students, who perceived psychiatric diagnosis as receiving higher priority than
      staff intended. The implications of these findings for curriculum planning are
      discussed. 

PMID- 24443193
TI  - The role and function of residents' organizations in psychiatry education.
AB  - Psychiatry residents' organizations have been poorly studied and variously
      portrayed as facilitative or regressive. A telephone survey of 19 residency
      programs of differing sizes in all major geographic regions revealed that 89% had
      some form of residents' organization. The groups are characterized by a wide
      range of structures, and they undertake a variety of tasks. The most common tasks
      are support, problem solving, and venting dissatisfaction. Problems frequently
      faced by such groups include changing resident constituencies, personality
      conflicts, authorization disputes, and representation and consensus problems.
      Strengths of such groups include their ability to help foster a sense of group
      identity; to provide a safe place to ventilate, work on problems, and fashion a
      consensus for the residents' input to the institution; and to offer training
      opportunities f or future psychiatric managers. 

PMID- 24443194
TI  - Medication backup in psychiatry residency programs.
AB  - All directors of U.S. adult psychiatry residency training programs (N = 202) were
      surveyed in 1988 about the practice of medication backup by trainees in their
      programs. Medication backup was defined as "the provision of medications by
      psychiatrists to patients receiving psychotherapy from nonphysicians." Of 110
      respondents, 94 of the programs (85%) had residents providing medication backup,
      the majority in the PGY-3 and -4 years. The university hospital inpatient service
      and the community mental health center outpatient clinic were the most common
      sites. Supervision was the most prevalent training method (84 programs), followed
      by lectures and seminars (45). Sixty-four program directors mewed medication
      backup as a useful and important function for the psychiatrist; 48 raised ethical
      concerns. Results point to the need for further investigation into the practice
      of medication backup in residency training. 

PMID- 24443195
TI  - Teaching consultation psychiatry through computerized case simulation.
AB  - The PsyConsult Adventure Simulation program presents a case simulation of
      consultation in a general hospital. Exploring this computerized case helps
      trainees prepare for the complexities of consultation that they will face on the
      hospital wards. The simulation provides a distinctive approach, modeling the
      process of an actual consultation and allowing trainees to explore on their own
      initiative. It presents general techniques of psychiatric consultation as well as
      specifics of diagnosis and treatment. The program demonstrates the feasibility of
      using case simulation with a personal computer system as a supplement to bedside
      teaching of consultation psychiatry. 

PMID- 24443196
TI  - Frequently asked questions about the american board of psychiatry and neurology.

PMID- 24443198
TI  - The journal club in psychiatric residency training.

PMID- 24443199
TI  - Recruitment for psychiatric residency.

PMID- 24443200
TI  - In reply.

PMID- 24443201
TI  - Erratum to: Pregnancy Ouring Psychiatry Residency: A Study of Attitudes.

PMID- 24443202
TI  - Microstructural origins of gadolinium-enhanced susceptibility contrast and
      anisotropy.
AB  - PURPOSE: MR histology based on magnetic susceptibility can be used to visualize
      diamagnetic myelin (and its deterioration) in the central nervous system and is
      facilitated by the application of high magnetic field strengths and paramagnetic
      contrast agents. Characterizing the effect of these tools will aid in assessing
      white matter myelin content and microstructure. METHODS: Image data from six
      gadolinium-perfused mouse brain specimens were acquired at 2.0, 7.0, and 9.4
      Tesla. Magnetic susceptibility contrast was analyzed for its dependence on field
      strength, gadolinium concentration, and white matter fiber orientation. A model
      for this contrast is presented based on the three-pool model for white matter.
      RESULTS: The specimen data illustrate that white-gray matter susceptibility
      contrast is field strength independent. White-gray matter contrast improves
      significantly as a function of gadolinium contrast agent in the tissue, i.e.,
      white matter appears increasingly more diamagnetic relative to gray matter. The
      simulated data from the model suggest that susceptibility anisotropy of white
      matter fiber bundles increases nonlinearly as a function of gadolinium
      concentration due to contrast agent compartmentalization into the extracellular
      white matter water pool. CONCLUSION: Using contrast agents in MR histology
      facilitates white-gray matter susceptibility contrast modulation and the probing
      of white matter microstructure and orientation.

PMID- 24443203
TI  - Laparoscopic total mesorectal excision for extraperitoneal rectal cancer: long
      term results of a 18-year single-centre experience.
AB  - BACKGROUND AND OBJECTIVES: The oncologic efficacy of laparoscopic total
      mesorectal excision (TME) for middle-low rectal cancer is still under discussion
      because of the few long-term data. This study reports the results arising from a
      single-institution experience during a 18-year period. METHODS: Data about 132
      consecutive laparoscopic TME performed between January 1994 and January 2012 were
      analysed with Kaplan-Meier method and a uni- and multi-variate analysis was
      conducted to define independent survival predictors. RESULTS: A total of 116
      sphincter-preserving operations and 16 abdominoperineal resections were
      performed. Postoperative mortality and morbidity were 0.8 and 18.2%, with a rate
      of anastomotic leakage of 13.8%. Average follow-up was 85.9 months (range 13
      210). Actuarial local recurrence rate was 4.13% at 5 years (any pelvic recurrence
      developed after 3 years from surgery). Overall and disease-free survival was
      respectively 83 and 79.8% at 5 years, 71 and 73% at 10 years and then remained
      constant until 18 years. Survival was correlated only to tumour stage and the
      type of surgery. CONCLUSIONS: Laparoscopic TME for extraperitoneal rectal cancer
      shows long-term oncologic outcomes similar to open rectal resections.

PMID- 24443204
TI  - Effect of body mass index in patients undergoing resection for gastric cancer: a
      single center US experience.
AB  - INTRODUCTION: With rising obesity in the USA, the impact of body mass index (BMI)
      on survival in gastric cancer remains unclear. METHODS: An institutional database
      of patients undergoing surgical evaluation for gastric cancer was reviewed.
      Patients were stratified by the following BMI: <18.5, 18.5-25, 25.1-30, and >30.
      Clinicopathologic factors and overall survival (OS) were analyzed. RESULTS: From
      1997 to 2012, 222 patients underwent exploration for gastric adenocarcinoma. 186
      (84%) had BMI recorded: nine (5%) <18.5, 72 (39%) 18.5-25, 62 (33%) 25.1-30, and
      43 (23%) >30. One hundred thirty-five (73%) ultimately underwent resection.
      Although American Society of Anesthesiology score and blood loss were not
      associated with increasing BMI, operative time was longer, p = 0.02. Proximal
      location, perineural invasion, lymphovascular invasion, positive surgical
      margins, and positive lymph nodes (LN+) were all associated with worse OS but not
      with increased BMI. Although increased BMI was associated with a lower lymph node
      count, p = 0.004, the number of LN + and final pathologic stage were not
      associated with BMI. Additionally, use of neoadjuvant or adjuvant chemotherapy
      was not associated with BMI. Median OS was 22 months. Median OS was improved with
      increased BMI: 21 months for <18.5, 13 months 18.5-25, 28 months 25-30, and 34
      months >30, p = 0.02. Disease-free survival (DFS) was similar: 2 months for
      <18.5, 7 months 18.5-25, 15 months 25.1-30, and 15 months >30, p = 0.02.
      CONCLUSION: Although BMI may impact the technical difficulty of resection for
      gastric cancer, increasing BMI is not associated with more advanced disease. In
      this experience, increased BMI does not adversely impact OS or DFS.

PMID- 24443205
TI  - Balance and randomness in sequential clinical trials: the dominant biased coin
      design.
AB  - Efron's biased coin design (BCD) is a well-known randomization technique that
      helps neutralize selection bias, while keeping the experiment fairly balanced for
      every sample size. Several extensions of this rule have been proposed, and their
      properties were analyzed from an asymptotic viewpoint and compared via
      simulations in a finite setup. The aim of this paper is to push forward these
      comparisons by taking also into account the adjustable BCD, which is never
      considered up to now. Firstly, we show that the adjustable BCD performs better
      than Efron's coin with respect to both loss of precision and randomness.
      Moreover, the adjustable BCD is always more balanced than the other coins and,
      only for some sample sizes, slightly more predictable. Therefore, we suggest the
      dominant BCD, namely a new and flexible class of procedures that can change the
      allocation rule step by step in order to ensure very good performance in terms of
      both balance and selection bias for any sample size. Our simulations demonstrate
      that the dominant BCD is more balanced and, at the same time, less or equally
      predictable than Atkinson's optimum BCD.

PMID- 24443206
TI  - NF-E2-related factor 2 promotes compensatory liver hypertrophy after portal vein
      branch ligation in mice.
AB  - Hepatectomy is a standard therapy that allows liver cancer patients to achieve
      long-term survival. Preceding hepatectomy, portal vein embolization (PVE) is
      frequently performed to increase the remnant liver size and reduce complications.
      Although the clinical importance of PVE is widely accepted, molecular mechanisms
      by which PVE leads to compensatory hypertrophy of nonembolized lobes remain
      elusive. We hypothesized that NF-E2-related factor 2 (Nrf2), a master regulator
      of cytoprotection, promotes compensatory liver hypertrophy after PVE. To address
      this hypothesis, we utilized three mouse lines and the portal vein branch
      ligation (PVBL) technique, which primarily induces the redistribution of the
      portal bloodstream in liver in a manner similar to PVE. PVBL was conducted in
      Kelch-like ECH-associated protein 1 (Keap1) conditional knockout (Keap1-CKO) mice
      in which Nrf2 is constitutively activated, along with Nrf2-deficient (Nrf2-KO)
      mice. We found that hypertrophy of nonligated lobes after PVBL was enhanced and
      limited in Keap1-CKO and Nrf2-KO mice, respectively, compared to wild-type mice.
      In Keap1-CKO mice, Nrf2 activity was increased, consistent with transient
      activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway,
      and reactive hepatocyte proliferation was significantly prolonged after PVBL.
      Importantly, Nrf2 activation by a chemical inducer was also effective for
      enhancement of hypertrophy after PVBL. CONCLUSION: Nrf2 supports compensatory
      liver hypertrophy after PVBL. This finding is particularly intriguing, because
      the primary effect of PVBL is limited to the alteration of bloodstream; this
      effect is much milder than changes resulting from hepatectomy, in which
      intrahepatic bloodstream and bile production cease. Our results suggest that
      premedication with an Nrf2 inducer may be a promising strategy to improve the
      outcome of PVE; this approach expands the indication of hepatectomy to patients
      with poorer liver function.

PMID- 24443207
TI  - Structural aspects of vectorial electron transfer in photosynthetic reaction
      centers.
AB  - Structural aspects of photosynthetic reaction centers in bacteria and plants are
      discussed in relation with the ability of these structures to perform a
      photoinduced electron transfer from one side of the membrane to the other. A
      comparison is made with recently synthesized artificial models. Functional
      similarities between the acceptor sides of bacterial and of Photosystem-II
      centers are utilized to hypothesize on their structure. 

PMID- 24443208
TI  - In vitro enzyme activities and products of (14)CO 2 assimilation in flag leaf and
      ear parts of wheat (Triticum aestivum L.).
AB  - Activities of key enzymes of Calvin cycle and C4 metabolism, rate of (14)CO2
      fixation in light and dark and the initial products of photosynthetic (14)CO2
      fixation were determined in flag leaf and different ear parts of wheat viz.
      pericarp, awn and glumes. Compared to the activities of RuBP carboxylase and
      other Calvin cycle enzymes viz. NADP-glyceraldehyde-3-phosphate dehydrogenase,
      NAD-glyceraldehyde-3-phosphate dehydrogenase and ribulose-5-phosphate kinase, the
      levels of PEP carboxylase and other enzymes of C4 metabolism viz. NADP-malate
      dehydrogenase, NAD-malate dehydrogenase, NADP-malic enzyme, NAD-malic enzyme,
      glutamate oxaloacetate transaminase genase, NADP-malic enzyme, NAD-malic enzyme,
      glutamate oxaloacetate transaminase and glutamate pyruvate transaminase, were
      generally greater in ear parts than in the flag leaf. In contrast to CO2 fixation
      in light, the various ear parts incorporated CO2 in darkness at much higher rates
      than flag leaf. In short term assimilation of (14)CO2 by illuminated ear parts,
      most of the (14)C was in malate with less in 3-phosphoglyceric acid, whereas flag
      leaves incorporated most into 3-phosphoglyceric acid. It seems likely that ear
      parts have the capability of assimilating CO2 by the C4 pathway of photosynthesis
      and utilise PEP carboxylase for recapturing the respired CO2. 

PMID- 24443209
TI  - RuP2 pool size indicated by CO2 assimilation following the abrupt loss of light.
AB  - Measurement of the changes in CO2 uptake by single leaves following the abrupt
      onset of darkness were made on sugarbeets (Beta vulgaris L.) and (Phaseolus
      vulgaris L.) The shape of the CO2 dark response curve was analyzed with respect
      to the reaction kinetics of CO2, RuP2 and RuP2 carboxylase. It was concluded that
      the net uptake of CO2 in the dark from a 1% O2 atmosphere can be approximately
      related to the pool size of the RuP2 substrate in the chloroplasts of C3 plants.
      This information was combined with CO2 levels and decay rates of the response
      curves to infer changes in carboxylase activity. Preliminary data are presented
      showing the relative concentration changes in RuP2 as light intensity decreases
      and as water stress increases. The method may prove useful in studies of plant
      response to environmental stresses. 

PMID- 24443210
TI  - Effect of light intensity on pigments and main acyl lipids during 'natural'
      chloroplast development in wheat seedlings.
AB  - The content and composition of pigments and acyl lipids (monogalactosyl
      diacylglycerol, digalactosyl diacylglycerol and phosphatidyl glycerol) have been
      investigated in developing chloroplasts isolated from successive 2-cm sections
      along the leaves of wheat seedlings grown either under 100, 30 or 3 W.m(-2). In
      all examined stages of plastid development chlorophyll a/b and
      chlorophyll/carotenoid ratios were higher with increasing irradiance, whereas
      chlorophyll content expressed on fresh weight basis gradually
      decreased.Concentrations of monogalactosyl diacylglycerol, digalactosyl
      diacylglycerol and phosphatidyl glycerol decreased per chlorophyll unit with
      increasing plastid maturity. The higher was the light intensity applied during
      plant growth, the higher were galactolipid and phosphatidyl glycerol contents in
      developing chloroplasts. During plastid development the percentage of alpha
      linolenic acid markedly increased in total and individual acyl lipids. Under high
      light conditions, the accumulation of this fatty acid proceeded more rapidly.
      Significantly higher proportion of alpha-linolenic acid was found in acyl lipid
      fraction of chloroplasts differentiating in high light grown plants, than in
      those from plants exposed to lower light intensities. The differences in the
      double bond index may indicate higher fluidity of thylakoid membranes in sun-type
      chloroplasts.Trans-3Delta-hexadecenoic acid, virtually absent in the youngest
      plastids, was found in much higher concentration (per chlorophyll unit and as mol
      % of phosphatidyl glycerol fatty acids) in chloroplasts developing at high light
      conditions. 

PMID- 24443211
TI  - Variation in the polypeptide composition of phycobilisomes from Anacystis
      nidulans and three pigment mutants.
AB  - Phycobilisomes, light harvesting antenna pigment systems, were studied from
      Anacystis nidulans wild type and from several spontaneous pigment mutants
      selected for improved growth in far-red light (>650 nm). This is the first
      characterization and description of polypeptide composition of phycobilisomes
      from spontaneous mutants (not chemically induced) of A. nidulans. The mutants had
      significant changes in the phycobiliprotein content relative to chlorophyll
      (Chl). Two phycobiliproteins, C-phycocyanin (lambdamax 625 nm) and
      allophycocyanin (lambdamax 650 nm) were present in a molar ratio of ~3:1 in the
      wild type. In the mutants the amount of allophycocyanin (APC) per cell remained
      constant but the phycocyanin (PC) content varied. Phycobilisomes of the mutants
      85Y, 19Y and 59G contained PC and APC in a molar ratio of 0.4:1, 0.7:1, and 1:1,
      respectively. Even though the phycobilisomes of mutant 85Y showed the greatest
      reduction in PC and consisted mostly of the APC core, the phycobilisomes were
      still functional and the growth rate of the 85Y cells was similar to the wild
      type. Fluorescence emission maxima of wild type and all the mutants were at 680
      nm (23 degrees C). Excitation maxima corresponded closely with expectations from
      absorption spectra. On SDS-PAGE gradient gels wild-type phycobilisomes had the
      usual 17-19 kD polypeptides of PC and APC, plus polypeptides at ca. 78, 56, 39,
      36 and 31 kD. Mutants 19Y and 85Y, with the greatest PC deficiency were also
      deficient in the 36 and 39 kD polypeptides, presumably due to a decrease in
      peripheral rod structures. Energetically functional hybrid phycobilisomes were
      obtained when complexes of phycoerythrin-phycocyanin from Nostoc were mixed with
      dissociated phycobilisomes of wild-type and mutant 85Y. The 31 kD polypeptide is
      common to both species and immunologically cross reactive. 

PMID- 24443212
TI  - Freezing damage and frost tolerance of the photosynthetic apparatus studied with
      isolated mesophyll protoplasts of Valerianella locusta L.
AB  - Mesophyll protoplasts were isolated from unhardened and cold-acclimated leaves of
      Valerianella locusta L. and subjected to freeze-thaw treatment. To evaluate the
      extent and course of freezing injury, photosynthetic reactions of whole
      protoplasts and of free thylakoid membranes, liberated from protoplasts by
      osmotic lysis, were measured. In addition, the integrity of the protoplasts was
      determined by microscopy. The results reveal an increased frost tolerance of
      protoplasts isolated from acclimated leaves with respect to all parameters
      measured. CO2-dependent O2 evolution (representing net photosynthetic CO2
      fixation of protoplasts) was the most freezing-sensitive reaction; its inhibition
      due to freeze-thaw treatment of protoplasts was neither correlated with
      disintegration of the plasma membrane, nor was it initiated by inactivation of
      the thylakoid membranes. The frost-induced decline of protoplast integrity was
      not closely correlated to thylakoid damage either. Freezing injury of the
      thylakoid membranes was manifested by inhibition of photosynthetic electron
      transport and photophosphorylation. Both photosystems were affected by freezing
      and thawing with strongest inhibition occurring in the water-oxidation system or
      at the oxidizing site of photosystem II. Photophosphorylation responded more
      sensitively to freezing stress than electron transport, although uncoupling
      (increased permeability of the thylakoid membranes to protons) was not a
      conspicuous effect. The data are discussed in relation to freezing injury in
      leaves and seem to indicate that frost damage in vivo is initiated at multiple
      sites. 

PMID- 24443213
TI  - Effects of water stress on the gas exchange, the activities of some enzymes of
      carbon and nitrogen metabolism, and on the pool sizes of some organic acids in
      maize leaves.
AB  - Water-stressed maize (Zea mays L.) leaves showed a large decrease in leaf
      conductance during photosynthesis. Net CO2 uptake and evaporation declined fast
      at mild stress (psi=-0.6 to -1.0 MPa) and slower at more severe stress (psi=-1.0
      to -1.2 MPa), whereas the CO2 concentration in the intercellular spaces (Ci) did
      not drop to the CO2 compensation point. The activities of the enzymes of
      photosynthetic carbon metabolism tested in this study dropped by approx. 30% at
      psi=-1.2 MPa. Glutamine synthetase activity was unaffected by water stress,
      whereas the activity of nitrate reductase was almost completely inhibited. The
      decline of enzyme activities in relation to psi was correlated with a concomitant
      decrease in the content of total soluble protein of the stressed leaves. The
      total leaf pools of malate, pyruvate and oxaloacetate decreased almost linearly
      in relation to psi, thus obviously contradicting the almost constant Ci. In
      comparison to the controls (psi=0.6 MPa) the content of citrate and isocitrate
      increaed markedly at psi=-0.9 MPa and decreased again at psi=-1.2 MPa. 

PMID- 24443214
TI  - Relative optical cross-section of the two photosystems during the life cycle of
      Chlorella.
AB  - Low-temperature fluorescence spectroscopy of Chlorella was used to monitor
      changes in photon utilization by the two photosystems during the life cycle.
      Changes in the relative optical cross-section sigma of the photosystems are
      brought about by changes in partition of the antenna molecules between the
      photosystems. The relative cross-section sigma is not affected by the State
      1/State 2 transitions. 

PMID- 24443215
TI  - CO2 enrichment in vitro. Effect on autotrophic and heterotrophic cultures of
      Nicotiana tabacum (var. Samsun).
AB  - Plantlets of Nicotiana tabacum (var. Samsun) were grown under CO2 enriched air
      supplied by a Warburg buffer. Growth of all plant parts was enhanced. The maximum
      growth increase was found for roots (120%).Addition of 30 g.l(-1) sucrose in the
      medium resulted in a three time faster growth. However, the effect of CO2
      enrichment was still positive in these conditions, although less pronounced than
      in autotrophic cultures. 

PMID- 24443216
TI  - Comparison of the structure and composition of the branchial filters in
      suspension feeding elasmobranchs.
AB  - The four, evolutionarily independent, lineages of suspension feeding
      elasmobranchs have two types of branchial filters. The first is a robust,
      flattened filter pad akin to a colander (e.g., whale sharks, mantas and devil
      rays) while the second more closely resembles the comb-like gill raker structure
      found in bony fishes (e.g., basking and megamouth sharks). The structure and the
      presence of mucus on the filter elements will determine the mechanical function
      of the filter and subsequent particle transport. Using histology and scanning
      electron microscopy, we investigated the anatomy of the branchial filters in 12
      of the 14 species of Chondrichthyian filter-feeding fishes. We hypothesized that
      mucus producing cells would be abundant along the filter epithelium and perform
      as a sticky mechanism to retain and transport particles; however, we found that
      only three species had mucus producing goblet cells. Two of these (Mobula kuhlii
      and Mobula tarapacana) also had branchial cilia, indicating sticky retention and
      transport. The remaining filter-feeding elasmobranchs did not have a sticky
      surface along the filter for particles to collect and instead must employ
      alternative mechanisms of filtration (e.g., direct sieving, inertial impaction or
      cross-flow). With the exception of basking sharks, the branchial filter is
      composed of a hyaline cartilage skeleton surrounded by a layer of highly
      organized connective tissue that may function as a support. Megamouth sharks and
      most of the mobulid rays have denticles along the surface of the filter,
      presumably to protect against damage from large particle impactions. Basking
      sharks have branchial filters that lack a cartilaginous core; instead they are
      composed entirely of smooth keratin.

PMID- 24443217
TI  - Support vector machine learning-based cerebral blood flow quantification for
      arterial spin labeling MRI.
AB  - PURPOSE: To develop a multivariate machine learning classification-based cerebral
      blood flow (CBF) quantification method for arterial spin labeling (ASL) perfusion
      MRI. METHODS: The label and control images of ASL MRI were separated using a
      machine-learning algorithm, the support vector machine (SVM). The perfusion
      weighted image was subsequently extracted from the multivariate (all voxels) SVM
      classifier. Using the same pre-processing steps, the proposed method was compared
      with standard ASL CBF quantification method using synthetic data and in-vivo ASL
      images. RESULTS: As compared with the conventional univariate approach, the
      proposed ASL CBF quantification method significantly improved spatial signal-to
      noise-ratio (SNR) and image appearance of ASL CBF images. CONCLUSION: the
      multivariate machine learning-based classification is useful for ASL CBF
      quantification.

PMID- 24443218
TI  - Characterization of surface electromyography using time domain features for
      determining hand motion and stages of contraction.
AB  - Surface electromyography (SEMG) signals can provide important information for
      prosthetic hand control application. In this study, time domain (TD) features
      were used in extracting information from the SEMG signal in determining hand
      motions and stages of contraction (start, middle and end). Data were collected
      from ten healthy subjects. Two muscles, which are flexor carpi ulnaris (FCU) and
      extensor carpi radialis (ECR) were assessed during three hand motions of wrist
      flexion (WF), wrist extension (WE) and co-contraction (CC). The SEMG signals were
      first segmented into 132.5 ms windows, full wave rectified and filtered with a 6
      Hz low pass Butterworth filter. Five TD features of mean absolute value,
      variance, root mean square, integrated absolute value and waveform length were
      used for feature extraction and subsequently patterns were determined. It is
      concluded that the TD features that were used are able to differentiate hand
      motions. However, for the stages of contraction determination, although there
      were patterns observed, it is determined that the stages could not be properly be
      differentiated due to the variability of signal strengths between subjects. 

PMID- 24443219
TI  - Technological advances in the hemostasis laboratory.
AB  - Automation is conventionally defined as the use of machines, control systems, and
      information technologies to optimize productivity. Although automation is now
      commonplace in several areas of diagnostic testing, especially in clinical
      chemistry and immunochemistry, the concept of extending this process to
      hemostasis testing has only recently been advanced. The leading drawbacks are
      still represented by the almost unique biological matrix because citrated plasma
      can only be used for clotting assays and few other notable exceptions, and by the
      highly specific pretreatment of samples, which is particularly distinct to other
      test systems. Despite these important limitations, a certain degree of automation
      is also now embracing hemostasis testing. The more relevant developments include
      the growing integration of routine hemostasis analyzers with track line systems
      and workcells, the development of specific instrumentation tools to enhance
      reliability of testing (i.e., signal detection with different technologies to
      increase test panels, plasma indices for preanalytical check of interfering
      substances, failure patterns sensors for identifying insufficient volume, clots
      or bubbles, cap-piercing for enhancing operator safety, automatic reflex testing,
      automatic redilution of samples, and laser barcode readers), preanalytical
      features (e.g., positive identification, automatic systems for tube(s) labeling,
      transillumination devices), and postphlebotomy tools (pneumatic tube systems for
      reducing turnaround time, sample transport boxes for ensuring stability of
      specimens, monitoring systems for identifying unsuitable conditions of
      transport). Regardless of these important innovations, coagulation/hemostasis
      testing still requires specific technical and clinical expertise, not only in
      terms of measurement procedures but also for interpreting and then appropriately
      utilizing the derived information. Thus, additional and special caution has to be
      used when designing projects of automation that include coagulation/hemostasis
      testing because peculiar and particular requirements must be taken into account. 

PMID- 24443220
TI  - In vitro evaluation of three-dimensional single-walled carbon nanotube composites
      for bone tissue engineering.
AB  - The purpose of this study was to develop three-dimensional single-walled carbon
      nanotube composites (SWCNT/PLAGA) using 10-mg single-walled carbon nanotubes
      (SWCNT) for bone regeneration and to determine the mechanical strength of the
      composites, and to evaluate the interaction of MC3T3-E1 cells via cell adhesion,
      growth, survival, proliferation, and gene expression. PLAGA (polylactic-co
      glycolic acid) and SWCNT/PLAGA microspheres and composites were fabricated,
      characterized, and mechanical testing was performed. MC3T3-E1 cells were seeded
      and cell adhesion/morphology, growth/survival, proliferation, and gene expression
      analysis were performed to evaluate biocompatibility. Imaging studies
      demonstrated microspheres with uniform shape and smooth surfaces, and uniform
      incorporation of SWCNT into PLAGA matrix. The microspheres bonded in a random
      packing manner while maintaining spacing, thus resembling trabeculae of
      cancellous bone. Addition of SWCNT led to greater compressive modulus and
      ultimate compressive strength. Imaging studies revealed that MC3T3-E1 cells
      adhered, grew/survived, and exhibited normal, nonstressed morphology on the
      composites. SWCNT/PLAGA composites exhibited higher cell proliferation rate and
      gene expression compared with PLAGA. These results demonstrate the potential of
      SWCNT/PLAGA composites for musculoskeletal regeneration, for bone tissue
      engineering, and are promising for orthopedic applications as they possess the
      combined effect of increased mechanical strength, cell proliferation, and gene
      expression.

PMID- 24443222
TI  - Spatiotemporal control of porcine p65RHD expression by advanced Tet-On system in
      PIEC cells helps regulate NFkB activity.
AB  - NFkB transcription activation leads to malfunction of endothelial cells, which is
      the main reason for pig xenograft rejection. Overexpression of a dominant
      negative mutant of porcine NFkappaB p65 (pp65RHD) could inhibit NFkB activation
      in endothelial cells. This study presents an advanced tetracycline-regulated
      system for pp65RHD spatiotemporal expression in porcine iliac endothelial cell
      line. In this system, an endothelial specific promoter ICAM-2 is used to improve
      pTet-On and internal ribosome entry site as well as enhanced green fluorescent
      protein (EGFP) elements are used to facilitate the result observation in pTRE
      Tight. Through transfection and drug selection, we obtained 7 single cell clones
      containing the advanced Tet-On system, in which pp65RHD expression is under tight
      regulated by doxycycline and can be visualized easily through EGFP. The
      distribution of induced pp65RHD was verified by immunocytochemical assays test.
      Then, NFkB activity was tested. Luciferase reporter assays showed that NFkB
      activity in two clones was influenced by the Dox-induced pp65RHD expression, but
      other clones weren't influenced. Therefore, we picked up 2 cell clones from the
      uninfluenced clones for further investigation by immunocytochemical assays and RT
      PCR detection. The final results supported the overexpression of pp65RHD in one
      clone could successfully inhibit NFkB activity. The success of pp65RHD
      spatiotemporal expression system is helpful to regulate NFkB activity and conquer
      cell-mediated immunity and could be used for preparation of transgenic pig,
      contributing to xenotransplantation. 

PMID- 24443221
TI  - Characterization of CYP1A2, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in South
      Brazilians.
AB  - Potential causes of variability in drug response include intrinsic factors such
      as ethnicity and genetic differences in the expression of enzymes that metabolize
      drugs, such as those from Cytochrome P450 (CYPs) superfamily. Pharmacogenetic
      studies search for genetic differences between populations since relevant alleles
      occur with varying frequencies among different ethnic populations. The Brazilian
      population is one of the most heterogeneous in the world, resulting from
      multiethnic admixture of Amerindians, Europeans, and Africans across centuries.
      Since the knowledge of CYP allele frequency distributions is relevant to
      pharmacogenetic strategies and these data are scarce in the Brazilian population,
      this study aimed to describe genotype and allele distributions of 15 single
      nucleotide polymorphisms (SNPs) at CYP 1A2, 2C19, 3A4, and 3A5 genes in African
      and European descents from South Brazil. A sample of 179 healthy individuals of
      European and African ancestry was genotyped by the MassARRAY SNP genotyping
      system. CYP3A5*3, CYP1A2*1F, CYP3A4*1B, and CYP2C19*2 were the most frequent
      alleles found in our sample. Significant differences in genotype and allelic
      distribution between African and European descents were observed for CYP3A4 and
      CYP3A5 genes. CYP3A4*1B was observed in higher frequency in African descents
      (0.379) than in European descents (0.098), and European descents showed higher
      frequency of CYP3A5*3 (0.810) than African descents (0.523). Our results indicate
      that only a few polymorphisms would have impact in pharmacogenetic testing in
      South Brazilians. Further studies with larger sample sizes are required also
      among other Brazilian regions. 

PMID- 24443223
TI  - Polymorphisms of VEGF, TGFbeta1, TGFbetaR2 and conotruncal heart defects in a
      Chinese population.
AB  - Genetic variants may determine susceptibility of congenital heart disease (CHD).
      To evaluate the impact of transforming growth factor-beta1 (TGFbeta1), TGFbeta
      receptor II (TGFbetaR2) and vascular endothelial growth factor (VEGF)
      polymorphisms on conotruncal heart defects susceptibility, we genotyped six
      functional polymorphisms TGFbeta1 rs1800469 C>T, TGFbetaR2 rs3087465 G>A, VEGF 
      2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of
      244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese
      population. Logistic regression analyses revealed that if the TGFbeta1 rs1800469
      CC homozygote genotype was used as the reference group, subjects carrying the CT
      variant heterozygote had a significant 0.48-fold decreased risk of conotruncal
      heart defects [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.30-0.88],
      subjects carrying the TT variant homozygote had a significant 0.47-fold decreased
      risk of conotruncal heart defects (OR 0.53; 95% CI 0.28-1.00). In stratification
      analyses, the TGFbeta1 rs1800469 C>T genotype was associated with a decreased
      risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95% CI 0.22
      0.99), a decreased risk for transposition of great artery in the dominant genetic
      model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95% CI
      0.24-0.83). Our findings suggest that TGFbeta1 rs1800469 C>T polymorphism was
      significantly associated with decreased risk of conotruncal heart defects.
      TGFbetaR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T
      polymorphisms may not play a role in the susceptibility of conotruncal heart
      defects.

PMID- 24443224
TI  - The mitochondrial 16 s rRNA reveals high anthropogenic influence on land snail
      diversity in a preliminary island survey.
AB  - A total of 30 specimens belonging to five species, namely; Cryptozona siamensis,
      Sarika resplendens and Sarika sp. from the family Ariophantidae as well as
      Quantula striata and Quantula sp. from the family Dyakiidae were collected from
      the Langkawi Island in Northern Peninsular Malaysia. All specimens were
      identified through comparisons of shell morphology and amplification of a 500 bp
      segment of the 16S rRNA mtDNA gene. To assess phylogenetic insights, the
      sequences were aligned using ClustalW and phylogenetic trees were constructed.
      The analyses showed two major lineages in both Maximum Parsimony and Neighbour
      Joining phylogenetic trees. Each putative taxonomic group formed a monophyletic
      cluster. Our study revealed low species and intraspecies genetic diversities
      based on the 16S rRNA gene sequences. Thus, this study has provided an insight of
      land snail diversity in populations of an island highly influenced by
      anthropogenic activities through complementary use of shell morphological and
      molecular data. 

PMID- 24443225
TI  - TP53 mutations in colorectal cancer from Tunisia: relationships with site of
      tumor origin, microsatellite instability and KRAS mutations.
AB  - Loss of TP53 function through gene mutation is a critical event in the
      development and progression of colorectal cancer (CRC). Here we examined 51
      primary CRC tumors from Tunisia for mutations in TP53 exons 4-9 using PCR-direct
      sequencing. TP53 status and mutation site/type were than correlated with nuclear
      protein accumulation, familial and clinicopathologic variables and data on KRAS
      mutations and microsatellite instability (MSI-H). The TP53 mutation analysis was
      possible in the tumor of 47 patients and a deleterious somatic mutation has been
      detected in 59.6% of the patients (28/47) including 20 (71.4%) missense
      mutations, 7 nonsense mutations (25%) and 1 (3.6%) frameshift mutation. 89.3%
      (25/28) of the detected mutations were in exons 5-8, whereas 10.7% (3/28) were in
      exon 4. Among the 27 non frameshift mutations, 89% (24/27) were transitions and
      11% (3/27) were transversions. 64.3% (18/27) of the altered amino acids
      corresponded to arginine. 74% (20/27) were G>C to A>T transitions, and more than
      half (14/27) occur at hotspots codons with CpG sites. TP53 mutations correlated
      closely with TP53 accumulation (p = 0.0090) and inversely with MSI phenotype (p =
      0.0658). A KRAS somatic mutation was identified in 25% (7/28) of the TP53 mutated
      tumors. All these mutations were G>A transitions in codon 12 and all the tumors
      with combined alterations but one were distally located and MSS. In conclusion,
      frequency and types of TP53 mutations and correlations with TP53 protein
      accumulation, and MSI were as reported for non-Tunisian patients. However, no
      significant associations have been detected between TP53 mutations and
      clinicopathological data in Tunisian patients as previously reported.

PMID- 24443226
TI  - Upregulation of the AT-hook DNA binding gene BoMF2 in OguCMS anthers of Brassica
      oleracea suggests that it encodes a transcriptional regulatory factor for anther
      development.
AB  - Ogura cytoplasmic male sterility (OguCMS) is the most important CMS system used
      for F1 hybrid cabbage production worldwide. The anther abortion and defective
      pollen development exhibited in OguCMS are coordinately regulated by the
      mitochondrial male sterile gene orf138 and many nuclear transcriptional
      regulatory factors. AT-hook DNA binding proteins regulate cell-specific gene
      expression. In this study, we cloned the gene encoding the AT-hook DNA binding
      protein BoMF2 using the cDNA-AFLP TDF sequence, which was upregulated in OguCMS
      cabbage flower buds, as a querying probe. BoMF2 contains a 783-nt continuous
      complete open reading frame encoding a 260 amino-acid polypeptide. In vivo
      transient expression assays using GFP fusions showed that BoMF2 protein was
      located in the nucleus. BoMF2 was preferentially expressed in cabbage stamens,
      with a short expression window at anther development stage 7-8. However, in
      OguCMS flowers, BoMF2 expression continued into the mature pollen stage and was
      concomitant with the continued proliferation of tapetum cells exhibited in this
      mutant. Arabidopsis plants overexpressing BoMF2 showed significantly shorter
      siliques than the wild type, as well as decrease of pollen viability. These
      results suggest that BoMF2, a transcriptional regulatory factor, might regulate
      tapetum proliferation during anther development.

PMID- 24443227
TI  - In vitro studies on the interaction between human serum albumin and fosfomycin
      disodium salt, an antibiotic drug by multi-spectroscopic and molecular docking
      methods.
AB  - The interaction between the human serum albumin (HSA) and drug, fosfomycin
      disodium salt (FOS) has been studied by different spectroscopic techniques. The
      experimental results showed a static quenching mechanism in the interaction of
      FOS with HSA. The number of binding sites, n and observed binding constant K a
      were measured by fluorescence quenching method. The thermodynamic parameters
      DeltaG degrees , DeltaH degrees  and DeltaS degrees  were calculated according to
      van't Hoff equation. The calculated distance r between FOS and the protein is
      evaluated according to the theory of Forster energy transfer. A change in the
      secondary structure of the protein was evident from the circular dichroism
      measurements, synchronous fluorescence and three-dimensional fluorescence
      spectra.

PMID- 24443228
TI  - Thyroid hormones association with depression severity and clinical outcome in
      patients with major depressive disorder.
AB  - The clinical implications of thyroid hormones in depression have been studied
      extensively and still remains disputable. Supplementation of thyroid hormones is
      considered to augment and accelerate antidepressant treatment. Studies on the
      role of thyroid hormones in depression deliver contradictory results. Here we
      assess theirs impact on depression severity and final clinical outcome in
      patients with major depression. Thyrotropin, free thyroxine (FT4), and free
      triiodothyronine (FT3) concentrations were measured with automated quantitative
      enzyme immunoassay. Depression severity and final clinical outcome were rated
      with 17-itemic Hamilton Rating Scale for Depression [HDRS(17)] and Clinical
      Global Impression Scales for severity and for improvement (CGIs, CGIi). FT3 and
      FT4 concentrations were significantly positively correlated with clinical
      improvement evaluated with CGIi (R = 0.38, P = 0.012; R = 0.33, P = 0.034,
      respectively). There was a significant correlation between FT4 concentrations and
      depression severity assessed in HDRS(17) (R = 0.31, P = 0.047). Male patients
      presented significantly higher FT3 serum levels (Z = 2.34, P = 0.018) and
      significantly greater clinical improvement (Z = 2.36, P = 0.018) when compared to
      female patients. We conclude that free thyroid hormones concentrations are
      associated with depression severity and have an impact on final clinical outcome.
      It can be more efficient to augment and accelerate the treatment of major
      depressive disorder with triiodothyronine instead of levothyroxine because of
      individual differences in thyroid hormones metabolism.

PMID- 24443229
TI  - Variation in the ovine hormone-sensitive lipase gene (HSL) and its association
      with growth and carcass traits in New Zealand Suffolk sheep.
AB  - The hormone-sensitive lipase (HSL) plays an important role in the regulation of
      lipolysis in adipose tissues, by catalysing a rate-limiting step in triglyceride
      hydrolysis. Variation within the human HSL gene (HSL) has been associated with an
      increased risk of obesity. In this study, variation within three regions (exon 3
      4, exon 5-6 and exon 9) of ovine HSL was investigated in 538 Suffolk lambs bred
      from 13 independent sires using PCR-SSCP. Four sequence variants of intron 5
      (designated A-D) and two variants of exon 9 (designated a and b) of ovine HSL
      were detected. No variation was found in exon 3-4 of the gene. The associations
      of the variation within ovine HSL with post-weaning growth and carcass traits
      including eye muscle depth (EMD), eye muscle width (EMW) and fat depth above the
      eye muscle (FDM) were assessed in 262 of the above 538 lambs using general linear
      mixed-effects models. In the single variant models, the presence of intron 5 A in
      a lamb's genotype was associated with reduced EMD (P = 0.036) and EMW (P =
      0.018), whereas the presence of intron 5 C was associated with increased EMD (P <
      0.001), EMW (P < 0.001) and FDM (P = 0.017). The association of C with increased
      EMD (P = 0.002) and EMW (P = 0.002) persisted in the multi-variant model. No
      association between HSL intron 5 variants and post-weaning growth, or between HSL
      exon 9 variants, post-weaning growth or carcass traits, were found.

PMID- 24443230
TI  - Interferon gamma and Interleukin 10 polymorphisms in Brazilian patients with
      systemic lupus erythematosus.
AB  - The pathogenesis of systemic lupus erythematosus (SLE) is complex, with several
      susceptibility genes and environmental factors involved in its development and
      clinical manifestation. Currently, there is a great amount of interest in the
      identification of biomarkers, as cytokines, that can quantify the susceptibility
      of SLE, the risk of future organ involvement, and association of their changes
      with disease activity. To investigate the associations between polymorphisms in
      the gene of Interferon gamma (IFN-gamma) and in the promoter of the Interleukin
      10 (IL-10) gene and SLE. The polymorphisms +874 T/A (rs2430561) in the IFN-gamma
      gene and -1082G/A (rs1800896) in the IL-10 promoter were determined in 99 SLE
      patients and 100 healthy controls among women Brazilian using the refractory
      mutation system polymerase chain reaction method. Disease activity was assessed
      using the SLE activity index. There were significant differences in the
      distribution of the genotype T/A in IFN-gamma gene polymorphism (+874) (chi (2) =
      7.168; P = 0.0074) and the genotype G/A in IL-10 promoter polymorphism (-1082)
      (chi (2) = 4.654; P = 0.0310) between the SLE and control groups. However, no
      association was observed between clinical features and the polymorphisms studied.
      This study presents preliminary evidence for association between IL-10 and IFN
      gamma polymorphism and SLE susceptibility, but not with clinical features in a
      Northeast population from Brazil.

PMID- 24443231
TI  - Association of genetic and non-genetic risk factors with the development of
      prostate cancer in Malaysian men.
AB  - There is growing global interest to stratify men into different levels of risk to
      developing prostate cancer, thus it is important to identify common genetic
      variants that confer the risk. Although many studies have identified more than a
      dozen common genetic variants which are highly associated with prostate cancer,
      none have been done in Malaysian population. To determine the association of such
      variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs
      found previously associated with various cancers which also included the prostate
      specific SNPs in a population based case control study (51 case subjects with
      prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and
      Indian ethnicity. We identified 21 SNPs significantly associated with prostate
      cancer. Among these, 12 SNPs were strongly associated with increased risk of
      prostate cancer while remaining nine SNPs were associated with reduced risk.
      However, data analysis based on ethnic stratification led to only five SNPs in
      Malays and 3 SNPs in Chinese which remained significant. This could be due to
      small sample size in each ethnic group. Significant non-genetic risk factors were
      also identified for their association with prostate cancer. Our study is the
      first to investigate the involvement of multiple variants towards susceptibility
      for PC in Malaysian men using genotyping approach. Identified SNPs and non
      genetic risk factors have a significant association with prostate cancer. 

PMID- 24443232
TI  - MiR-320a down-regulation mediates bladder carcinoma invasion by targeting ITGB3.
AB  - To investigate whether the miR-320a could regulate bladder cancer cells invasion
      by down-regulation of ITGB3. Real-time quantitative PCR was applied to evaluate
      the expression level of miRNA-320a in bladder transitional cell carcinomas (TCC)
      and normal bladder transitional cell (NBTC) samples. The invasion ability of miR
      320a in TCC T24 cells was analyzed by Transwell assay after pre-miR-320a or anti
      miR-125b transfection. For the invasion mechanism analysis of miR-320a on T24
      cells, TargetScan, PicTar and miRBase were used to predict the possible target
      gene of miR-320a. Luciferase activities assay and western blot were used to
      reveal the predicted target gene of miR-320a were direct and specific. RNA
      interference technology was used to confirm the invasion inhibition of miR-320a
      was directly induced by ITGB3. Our study showed that miR-320a was down-regulated
      in human TCC specimens compared to that in NBTC specimens. Over-expression of miR
      320a in T24 cells inhibited TCC invasion and this inhibitory effect on T24 cells
      could be restore by miR-320a knocked down. Mechanism analysis revealed that ITGB3
      was a direct and specific target of miR-320a. The advanced effect of anti-miR
      320a on TCC cell invasion was mediated by expression silence of ITGB3. In
      summary, aberrantly expressed miR-320a contribute to T24 cells invasion partly
      through directly down-regulating ITGB3 protein expression in TCC and this miRNA
      signature offers a novel potential therapeutic strategy for TCC.

PMID- 24443233
TI  - Study of the spatial correlation between neuronal activity and BOLD fMRI
      responses evoked by sensory and channelrhodopsin-2 stimulation in the rat
      somatosensory cortex.
AB  - In this work, we combined optogenetic tools with high-resolution blood
      oxygenation level-dependent functional MRI (BOLD fMRI), electrophysiology, and
      optical imaging of cerebral blood flow (CBF), to study the spatial correlation
      between the hemodynamic responses and neuronal activity. We first investigated
      the spatial and temporal characteristics of BOLD fMRI and the underlying neuronal
      responses evoked by sensory stimulations at different frequencies. The results
      demonstrated that under dexmedetomidine anesthesia, BOLD fMRI and neuronal
      activity in the rat primary somatosensory cortex (S1) have different frequency
      dependency and distinct laminar activation profiles. We then found that localized
      activation of channelrhodopsin-2 (ChR2) expressed in neurons throughout the
      cortex induced neuronal responses that were confined to the light stimulation S1
      region (<500 MUm) with distinct laminar activation profile. However, the spatial
      extent of the hemodynamic responses measured by CBF and BOLD fMRI induced by both
      ChR2 and sensory stimulation was greater than 3 mm. These results suggest that
      due to the complex neurovascular coupling, it is challenging to determine
      specific characteristics of the underlying neuronal activity exclusively from the
      BOLD fMRI signals.

PMID- 24443234
TI  - Spatiotemporal changes in NSF expression of DRG neurons in a rat model of spinal
      nerve ligation.
AB  - N-ethylmaleimide-sensitive fusion (NSF) protein is a homohexameric ATPase that
      binds to the GluR2 subunit of alpha-amino-3-hydroxy-5-methyl-4
      isoxazoleproprionic acid (AMPA) receptors. The stability and movement of AMPA
      receptors at synapses are important factors that control synaptic strength. NSF
      is involved in the surface expression regulation of AMPA receptors and
      consequently synaptic activity. Reduced expression of NSF or reduced interaction
      of NSF with GluR2 leads to a number of neurological disorders. Using a rat model
      of L5 spinal nerve ligation (SNL), we investigated the temporal and spatial
      expression of NSF in injured L5 and uninjured L4 dorsal root ganglion (DRG)
      neurons during mechanical allodynia. L5 SNL led to a significant decrease of NSF
      in both L4 and L5 DRGs observed at 3, 7, and 14 days after injury. In particular,
      NSF expression in calcitonin gene-related peptide (CGRP)-immunoreactive (IR) and
      IB4-IR neurons was reduced, whereas NSF expression in NF-200-IR neurons remained
      unaltered. These results indicate a role for NSF in CGRP-IR and IB4-IR neurons in
      SNL, with reduced NSF expression possibly contributing to SNL derived neuropathic
      pain.

PMID- 24443236
TI  - The mind-brain problem, epistemology, and psychiatric education.
AB  - The mind-brain problem is the fundamental mystery in psychiatry and the chief
      obstacle to a coherent curriculum for its students. Rather than acknowledge the
      problem as a source of ambiguity and discord, some educators have attempted to
      abolish, finesse, or ignore it. An alternative to these tactics is found in the
      epistemological approach taken by Karl Jaspers and others, which seeks to
      determine what we know and how we know it. Educational programs based on such an
      approach seem more likely than others to produce students who are broad-minded,
      tough-minded, and fair-minded. 

PMID- 24443235
TI  - Vasostatin-1 antigenic epitope mapping for induction of cellular and humoral
      immune responses to chromogranin A autoantigen in NOD mice.
AB  - The chromogranin A (ChgA) 29-42 sequence is the antigenic epitope for the BDC2.5
      CD4(+) T-cell receptor in NOD mice (H-2(g7) ). We have now characterized the
      binding register of the ChgA 29-42 peptide for the I-A(g7) molecule. Truncation
      of the peptide demonstrated that the KCVLEVISD sequence 34-42 is the binding
      register and extension of this sequence by flanking residues increased its
      binding affinity and antigenic capacity. We employed anti-ChgA peptide antibodies
      generated against different fragments of ChgA for immunostaining of pancreatic
      islet sections from NOD mice. A strong immuno-staining pattern was observed for
      the ChgA 17-38 peptide antibodies that overlap with the ChgA 29-42 sequence.
      Moreover, sera from diabetic NOD mice showed elevated titers of autoantibodies to
      the ChgA 29-42 peptide. These findings indicate that peptides from the N-terminal
      region of ChgA are able to induce cellular and humoral immune responses in NOD
      mice. 

PMID- 24443237
TI  - Gay and lesbian issues in residency training at u.s. Psychiatry programs.
AB  - The authors conducted a survey that explored the training milieu of gay and
      lesbian psychiatric residents at various sites throughout the United States. In
      some ways, the residents surveyed have greater institutional support than was
      found in an earlier study of homosexual medical students. But there are clear and
      disturbing differences among residents based on gender, with men more likely than
      women to consider their program supportive of their sexual orientation. In spite
      of this relative advantage, gay men and lesbians, medical students and residents
      alike, would prefer that their training institutions be more supportive of their
      sexuality and more adept at facilitating sensitive care of homosexual patients. 

PMID- 24443238
TI  - Gender differences in faculty retention and rank attainment in academic
      departments of psychiatry.
AB  - Using 1989 data from the Faculty Roster System of the Association of American
      Medical Colleges, the authors examined gender differences in retention and rank
      attainment of psychiatry faculty who had received their first full-time medical
      school appointments in 1978. Retention differences between men and women were not
      significant in either the M.D. or the Ph.D. subgroup. Women M.D.'s in the sample
      had advanced through the academic ranks to a significantly lesser extent than had
      men M.D.'s; the rank attainment differences among Ph.D.'s, however, were not
      significant. These results underscore the need for more study of gender
      differences in the career paths of faculty in academic psychiatry departments. 

PMID- 24443239
TI  - Correlates of psychiatry grand rounds attendance.
AB  - Although grand rounds is an important educational conference in most medical
      schools and psychiatry departments, there have been few studies of which
      variables influence faculty and trainee attendance. The authors hypothesized that
      psychiatry grand rounds attendance would be affected by content area, the
      speaker's discipline and geographic origin, and the label of "research" in the
      presentation title. In 3 years of grand rounds presentations at the Baylor
      College of Medicine Department of Psychiatry and Behavioral Sciences, fewer
      residents attended grand rounds when "research" was in the label and attendance
      was greater when the rounds were cosponsored by another agency, presented in
      honor of someone, or given by an out-of-town speaker. 

PMID- 24443240
TI  - Development of junior faculty in resource-poor departments of psychiatry.
AB  - Junior faculty are required to develop steady, productive academic and research
      programs in order to stay on an academic track and be promoted. In departments
      that are not research centers, quite often new, aspiring faculty do not have the
      time, skills, training, and the encouraging environment necessary to meet these
      demands. Quantitatively, research-poor departments provide clinical services to
      the majority of patients in the United States and psychiatric training to a large
      number of medical students and residents. It is quite widely accepted that
      enhancement of academic education in these departments is needed. Currently,
      however, most suggestions to increase research in such departments have been
      initiated from the research center's perspective. In this study, the problem is
      illuminated from the faculty's perspective in resource-poor departments.
      Solutions are discussed and new approaches are suggested. 

PMID- 24443241
TI  - Medical students' attitudes toward a state hospital.
AB  - To expose medical students to public psychiatry and destigmatize their attitudes
      about state hospitals, third-year medical students in a psychiatric clerkship
      were assigned to a 1-day visit at a nearby state mental hospital Over a 2-year
      period (1988-1990), the medical students' attitudes toward state hospitals were
      measured before and after the visit. Of the 188 survey pairs (measurements of the
      students' pre- and post-visit attitudes) that were distributed, 173 pairs were
      collected. The students reported more favorable views after the visit on four of
      seven items. Because attitudes about psychiatry continue to develop during
      clerkships, medical students should be afforded broad exposure to career options
      in psychiatry, including site visits to state mental hospitals. 

PMID- 24443242
TI  - Using the objective structured clinical examination in a psychiatry residency.
AB  - Evaluation of psychiatric residents' clinical skills and knowledge is important
      to assure faculty that residents are achieving competence. Because psychiatric
      residents perform many activities without direct observation, it is necessary to
      construct techniques that allow careful objective evaluation of their
      performance. This article describes how one residency program developed an
      Objective Structured Clinical Examination (OSCE) to assess the clinical skills of
      its PGY-2 and PGY-4 psychiatric residents. 

PMID- 24443243
TI  - Frequently asked questions about the residency review committee.

PMID- 24443245
TI  - Attending Psychiatrists' vs. Residents' Knowledge of Geriatric Depression.

PMID- 24443246
TI  - The postresidency perspective of the psychiatric chief resident.

PMID- 24443247
TI  - Photochemistry of alpha-diketones in carbohydrates: anomalous Norrish type II
      photoelimination and Norrish-Yang photocyclization promoted by the internal
      carbonyl group.
AB  - A series of four alpha-diketones placed as 1alpha-pyruvoyl tethers on D
      glucopyranose and D-glucopyranosiduronic acid skeletons was prepared in order to
      determine the influence of captodative and stereoelectronic effects on the
      regioselectivity of the hydrogen atom transfer (HAT) in Norrish type II
      photochemical processes. We observed that the 1,5-HAT regioselectivity can be
      switched between the two potentially abstractable syn-1,3-diaxial hydrogens at H6
      and H8. Highly unusual photoproducts from Norrish type II photoelimination and
      Norrish-Yang photocyclization initiated by the excited internal carbonyl group
      were obtained, in some cases in excellent synthetic yield. The 1,5-HAT transition
      state in the Norrish type II photoelimination was investigated by photochemical
      experiments in the crystalline state. 

PMID- 24443248
TI  - Acceleration of high angular and spatial resolution diffusion imaging using
      compressed sensing with multichannel spiral data.
AB  - PURPOSE: To accelerate the acquisition of simultaneously high spatial and angular
      resolution diffusion imaging. METHODS: Accelerated imaging is achieved by
      recovering the diffusion signal at all voxels simultaneously from under-sampled k
      q space data using a compressed sensing algorithm. The diffusion signal at each
      voxel is modeled as a sparse complex Gaussian mixture model. The joint recovery
      scheme enables incoherent under-sampling of the 5-D k-q space, obtained by
      randomly skipping interleaves of a multishot variable density spiral trajectory.
      This sampling and reconstruction strategy is observed to provide considerably
      improved reconstructions than classical k-q under-sampling and reconstruction
      schemes. The complex model enables to account for the noise statistics without
      compromising the computational efficiency and theoretical convergence guarantees.
      The reconstruction framework also incorporates compensation of motion induced
      phase errors that result from the multishot acquisition. RESULTS: Reconstructions
      of the diffusion signal from under-sampled data using the proposed method yields
      accurate results with errors less that 5% for different accelerations and b
      values. The proposed method is also shown to perform better than standard k-q
      acceleration schemes. CONCLUSIONS: The proposed scheme can significantly
      accelerate the acquisition of high spatial and angular resolution diffusion
      imaging by accurately reconstructing crossing fiber architectures from under
      sampled data.

PMID- 24443250
TI  - New density estimates of a threatened sifaka species (Propithecus coquereli) in
      Ankarafantsika National Park.
AB  - Propithecus coquereli is one of the last sifaka species for which no reliable and
      extensive density estimates are yet available. Despite its endangered
      conservation status [IUCN, 2012] and recognition as a flagship species of the
      northwestern dry forests of Madagascar, its population in its last main refugium,
      the Ankarafantsika National Park (ANP), is still poorly known. Using line
      transect distance sampling surveys we estimated population density and abundance
      in the ANP. Furthermore, we investigated the effects of road, forest edge, river
      proximity and group size on sighting frequencies, and density estimates. We
      provide here the first population density estimates throughout the ANP. We found
      that density varied greatly among surveyed sites (from 5 to ~100 ind/km2) which
      could result from significant (negative) effects of road, and forest edge, and/or
      a (positive) effect of river proximity. Our results also suggest that the
      population size may be ~47,000 individuals in the ANP, hinting that the
      population likely underwent a strong decline in some parts of the Park in recent
      decades, possibly caused by habitat loss from fires and charcoal production and
      by poaching. We suggest community-based conservation actions for the largest
      remaining population of Coquerel's sifaka which will (i) maintain forest
      connectivity; (ii) implement alternatives to deforestation through charcoal
      production, logging, and grass fires; (iii) reduce poaching; and (iv) enable long
      term monitoring of the population in collaboration with local authorities and
      researchers.

PMID- 24443251
TI  - An in vitro study into the effect of zinc substituted hydroxyapatite on
      osteoclast number and activity.
AB  - Zinc ions have been shown to inhibit osteoclast development and proliferation
      both in vitro and in vivo. The same inhibiting effect has been observed in vitro
      when zinc was substituted into tri-calcium phosphate (TCP). Because of the
      solubility of TCP it is not an ideal candidate for a material to inhibit
      osteoclast activity in the long term. Hydroxyapatite (HA) is less soluble and so
      potentially offers a more long-term, sustainable effect. Previous work has shown
      that zinc can successfully be substituted into HA and still retain phase purity
      after heat treatment. The study reported here presents the effects of zinc
      substituted HA on the development and activity of osteoclast-like cells. It was
      found that increasing zinc substitution levels led to a decrease in the number of
      these cells present after 21 days. When resorption activity was investigated it
      was found that an increase in the amount of zinc present in the discs led to a
      significant decrease in the amount of resorption taking place on the discs. These
      results provide evidence for the potential of zinc substituted HA as a material
      to reduce resorptive activity to provide long-term bonding of implant to bone.

PMID- 24443249
TI  - Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis:
      methodological issues of a randomized controlled trial.
AB  - Multiple recent Sickle Cell Disease studies have been terminated due to poor
      enrollment. We developed methods to overcome past barriers and utilized these to
      study the efficacy and safety of intravenous magnesium for vaso-occlusive crisis
      (VOC). We describe the methods of the Intravenous Magnesium in Sickle Vaso
      occlusive Crisis (MAGiC) trial and discuss methods used to overcome past
      barriers. MAGiC was a multi-center randomized double-blind placebo-controlled
      trial of intravenous magnesium versus normal saline for treatment of VOC. The
      study was a collaboration between Pediatric Hematologists and Emergency
      Physicians in the Pediatric Emergency Care Applied Research Network (PECARN).
      Eligible patients were randomized within 12 hours of receiving intravenous
      opioids in the Emergency Department (ED) and administered study medication every
      8 hours. The primary outcome was hospital length of stay. Associated plasma
      studies elucidated magnesium's mechanism of action and the pathophysiology of
      VOC. Health-related quality of life was measured. Site-, protocol-, and patient
      related barriers from prior studies were identified and addressed. Limited study
      staff availability, lack of collaboration with the ED, and difficulty obtaining
      consent were previously identified barriers. Leveraging PECARN resources, forging
      close collaborations between Sickle Cell Centers and EDs of participating sites,
      and approaching eligible patients for prior consent helped overcome these
      barriers. Participation in the PECARN network and establishment of collaborative
      arrangements between Sickle Cell Centers and their affiliated EDs are major
      innovative features of the MAGiC study that allowed improved subject capture.
      These methods could serve as a model for future studies of VOCs.

PMID- 24443252
TI  - Quantitative analysis of orofacial development and median clefts in Xenopus
      laevis.
AB  - Xenopus has become a useful tool to study the molecular mechanisms underlying
      orofacial development. However, few quantitative analyses exist to describe the
      anatomy of this region. In this study we combine traditional facial measurements
      with geometric morphometrics to describe anatomical changes in the orofacial
      region during normal and abnormal development. Facial measurements and principal
      component (PC) analysis indicate that during early tadpole development the face
      expands primarily in the midface region accounting for the development of the
      upper jaw and primary palate. The mouth opening correspondingly becomes flatter
      and wider as it incorporates the jaw elements. A canonical variate analysis of
      orofacial and mouth opening shape emphasized that changes in the orofacial shape
      occur gradually. Orofacial anatomy was quantified after altered levels of
      retinoic acid using all-trans retinoic acid or an inhibitor of retinoic acid
      receptors or by injecting antisense oligos targeting RALDH2. Such perturbations
      resulted in major decreases in the width of the midface and the mouth opening
      illustrated in facial measurements and a PC analysis. The mouth opening shape
      also had a gap in the primary palate resulting in a median cleft in the mouth
      opening that was only illustrated quantitatively in the morphometric analysis.
      Finally, canonical and discriminant function analysis statistically distinguished
      the orofacial and mouth opening shape changes among the different modes used to
      alter retinoic acid signaling levels. By combining quantitative analyses with
      molecular studies of orofacial development we will be better equipped to
      understand the complex morphogenetic processes involved in palate development and
      clefting.

PMID- 24443253
TI  - Buy one - get one free!

PMID- 24443255
TI  - Clinical significance and biological roles of CARMA3 in human bladder carcinoma.
AB  - Caspase recruitment domain and membrane-associated guanylate kinase-like domain
      protein 3 (CARMA3) was reported as an oncoprotein overexpressed in several
      cancers. The expression pattern of CARMA3 and its clinical significance in human
      bladder cancer have not been well characterized. In the present study, CARMA3
      expression was analyzed in 90 archived bladder cancer specimens using
      immunohistochemistry, and the correlation between CARMA3 expression and
      clinicopathological parameters was evaluated. We found that CARMA3 was
      overexpressed in 35 of 90 (38.8%) bladder cancer specimens. Significant
      association was observed between CARMA3 overexpression with tumor status (p =
      0.081) and tumor grade (p = 0.027). To further explore the biological functions
      of CARMA3 in bladder cancer, we depleted CARMA3 in T24 and 5637 cell lines using
      small interfering RNA (siRNA). Using cell counting kit-8 (CCK8) assay and colony
      formation assay, we were able to show that CARMA3 depletion inhibited cell
      proliferation and colony number. Further study demonstrated that CARMA3 depletion
      decreased an expression of nuclear factor kappa B (NF-kappaB) targets cyclin D1
      and Bcl-2 expression, as well as IkappaB phosphorylation. Luciferase reporter
      assay showed that CARMA3 depletion could downregulate NF-kappaB reporter
      activity. In conclusion, CARMA3 is overexpressed in bladder cancer and regulates
      malignant cell growth and NF-kappaB signaling, which makes CARMA3 a candidate
      therapeutic target for bladder cancer.

PMID- 24443256
TI  - Nestin: predicting specific survival factors for breast cancer.
AB  - The purpose of this study is to investigate the relationship between nestin
      expression and clinicopathological characteristics, immunohistochemical markers
      and to determine the prognostic impact of nestin expression in breast cancer so
      as to lay a foundation for the treatment of breast cancer. A total of 109
      patients who were histologically diagnosed with breast cancer and underwent
      radical operations from January 2006 to September 2007 in China Medical
      University were enrolled in the study. Nestin protein expression was evaluated by
      immunohistochemistry. The relationship between nestin and other parameters was
      analyzed by using chi-square test and Fisher's exact test. Nestin expression was
      observed in 37.6% (41/109) of cases. There were no significant differences
      between the age of >40 and <=40 years group in terms of nestin expression (39.8
      vs 18.2%; P = 0.161). The rate of nestin expression between those with and
      without lymph node metastasis was not significantly different (X (2) = 0.086; P =
      0.769). The 5-year survival rates of the patients with nestin expression and
      those without were 34.1% (14/41) and 55.9% (38/68), respectively (P = 0.028).
      Overall, triple-negative breast cancers had higher expression rates than other
      cancers (54.1 vs 29.2%; P = 0.011). Nestin expression rate in ER- and PR-negative
      tumors was found to be significantly higher than cases that were ER- and PR
      positive (P = 0.011 and P = 0.036, respectively). However, it was not found that
      HER2 expression was related to nestin expression (P = 0.120). These results
      suggest that the expression of nestin might play an important role in the
      prognosis of breast carcinoma, especially in the triple-negative subgroups.

PMID- 24443257
TI  - ERCC1 and BRCA1 mRNA expressions are associated with clinical outcome of non
      small cell lung cancer treated with platinum-based chemotherapy.
AB  - We conducted a perspective study to investigate whether the expression of
      excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group G
      (XPG), breast cancer 1 (BRCA1), and ribonucleotide reductase M1 (RRM1) is
      correlated with clinical outcome of non-small cell lung cancer (NSCLC). Patients
      with histologically confirmed inoperable stages IIIB and IV NSCLC were collected
      and followed up until January 2012. Relative cDNA quantification for ERCC1, XPG,
      BRCA1, and RRM1 was performed using a fluorescence-based, real-time detection
      method. Cox regression analysis indicated that a high level of ERCC1 was
      associated with shorter overall survival (OS) and progression-free survival (PFS)
      times when compared with low expression, with adjusted hazard ratios (HRs) (95%
      confidence interval (CI)) of 2.25 (1.18-4.39) and 2.63 (1.33-5.25), respectively.
      High expression of BRCA1 was correlated with shorter OS and PFS times when
      compared with low expression, and the adjusted HRs (95% CI) were 3.29 (1.72-6.39)
      and 5.94 (2.80-13.06), respectively. Moreover, we found a significant correlation
      between BRCA1 expression and age (chi(2) = 4.14, P = 0.04) and stage (chi(2) =
      5.26, P = 0.02). Our results suggest that ERCC1 and BRCA1 mRNA expressions are
      associated with PFS and OS in advanced NSCLC patients treated with platinum-based
      chemotherapy.

PMID- 24443258
TI  - Heterogeneity in chloroplast photosystem II.
AB  - Photosystem-two (PSII) in the chloroplasts of higher plants and green algae is
      not homogeneous. A review of PSII heterogeneity is presented and a model is
      proposed which is consistent with much of the data presented in the literature.
      It is proposed that the non-quinone electron acceptor of PSII is preferentially
      associated with the sub-population of PSII known as PSIIbeta. 

PMID- 24443259
TI  - Ontogenetic changes in photosynthetic capacity and dry matter production of flag
      wheat leaves during the grain filling period.
AB  - The relationships between photosynthetic capacity and dry matter accumulation
      during the grain filling period have been studied in flag leaves of Triticum
      aestivum L., cv. Kolibri grown in Mediterranean field conditions. Particular
      importance has been given to assimilate accumulation in relation to the onset of
      senescence. During grain filling, the time course of specific dry weight (SDW)
      was similar in the blade and in the sheath. Variations in SDW were about six
      times larger in the sheath than in the blade. Minimum blade SDW values occurred
      during heading and at anthesis. Maximum blade SDW values were observed two weeks
      after anthesis. After this, SDW values decreased sharply. The dry matter increase
      per grain in the period from two weeks after anthesis to the end, was only about
      25% of final grain dry weight. The importance of environmental constraints on
      maximum SDW values are discussed. Maximum SDW values occurred at the beginning of
      the period of rapid decline in blade net CO2 assimilation rate and leaf nitrogen
      content, that is, at the beginning of senescence. On the other hand, the stomatal
      resistance to CO2 and the development of senescence are not apparently related.
      The maximum blade dry weight increase (considering a value of zero at heading)
      was about 60 mg dry weight per g fresh weight. The possible relationships between
      dry matter accumulation and senescence onset are discussed. 

PMID- 24443260
TI  - Reconstitution of energy transfer and electron transfer between solubilised
      pigment-protein complexes from thylakoid membranes. The role of acyl lipids.
AB  - Solubilisation of thylakoid membranes from young leaves of Pisum sativum in the
      presence of Triton X-100 resulted in an almost complete loss of quenching of
      light-harvesting chlorophyll-protein (LHCP) fluorescence, as measured at 77
      degrees K. There were concomitant changes in the kinetics of light-saturation
      curves of electron transport from 2,6-dichlorophenolindophenol/ascorbate to
      methyl viologen. These effects were accompenied by a physical dissociation of
      LHCP polypeptides from photosystem I (PSI) and photosystem II (PSII)
      polypeptides, as determined by polyacrylamide gel-electrophoresis. Detergent
      dialysis in the presence of exogenous purified galactolipids, about 80% of which
      were linoleoyl molecular species, only partially reversed these effects. However,
      detergent-dialysis using the phospholipids, phosphatidylglycerol and
      phosphatidylcholine, resulted in the substantial restoration of 77 degrees K
      fluorescence quenching and the restoration of both emission spectra and electron
      transport kinetics of both Photosystems I and II that were typical of native
      membranes. 

PMID- 24443261
TI  - Photooxidative reactions in chloroplast thylakoids. Evidence for a Fenton-type
      reaction promoted by superoxide or ascorbate.
AB  - A methyl viologen (MV)(*) mediated Mehler reaction was studied using Type C and D
      chloroplasts (thylakoids) from spinach. The extent of photooxidative reactions
      were measured as (a) rate of ethylene formation from methional oxidation
      indicating the production of oxygen radicals, and (b) rate of malondialdehyde
      (MDA) formation as a measure of lipid peroxidation. Without added ascorbate, 1
      MUM FerricEDTA increased ethylene formation by greater than 4-fold, but had no
      effect on MDA production. Ascorbate (1 mM) produced a tripling of ethylene while
      it reduced MDA formation in the presence of iron. Radical scavengers
      diethyldithiocarbamate (DDTC), formate, 1,4-diazabicyclo (2.2.2octane) (DABCO),
      inhibited ethylene formation. Using 0,4 M mannitol to scavenge hydroxyl radicals,
      the rates of ethylene formation were reduced 40 to 60% with or without 1 MUM
      Fe(III) EDTA. The strong oxidant(s) not scavenged by mannitol are hypothesized to
      be either alkoxyl radicals from lipid peroxidation, or 'site specific' formation
      of hydroxyl radicals in a lipophillic environment not exposed to mannitol.
      Singlet oxygen does not appear to be a significant factor in this system.
      Catalase strongly inhibited both ethylene and MDA synthesis under all conditions;
      1 mM ascorbate did not reverse this inhibition. However, the strong superoxide
      dismutase (SOD) inhibition of ethylene and MDA formation was completely reversed
      by 1 mM ascorbate. This suggests that superoxide was functioning as an iron
      reducing agent and that in its absence, ascorbate was similarly promoting
      oxidations. Therefore, these oxidative processes were dependent on the presence
      of H2O2 and a reducing agent, suggesting the involvement of a Fenton-type
      reaction. 

PMID- 24443262
TI  - Variation in photosynthetic electron transport capacity in vivo and its effects
      on the light modulation of ribulose bisphosphate carboxylase.
AB  - Photosynthetic electron transport capacity was varied in vivo in sugar beets
      using iron deficiency, and its effects on the light modulation of ribulose
      bisphosphate carboxylase (RuBPCase) studied. Three treatment groups corresponding
      to decreasing amounts of thylakoids per leaf area were examined: iron sufficient
      (control), moderately iron-stressed, and severely iron-stressed. Reduction in
      electron transport capacity in vivo was correlated with a substantial decrease in
      the level of RuBPCase activation, even at saturating irradiances. These results
      indicate a direct relationship between RuBPCase activation and photosynthetic
      electron transport. In addition, our data suggest that the activation of RuBPCase
      could not solely account for the increases in the photosynthetic rate at high
      irradiances; RuBPCase reached maximal activation at irradiances well below light
      saturation for net photosynthesis. 

PMID- 24443263
TI  - Polar lipid composition of chloroplast thylakoids isolated from leaves grown
      under different lighting conditions.
AB  - The polar acyl lipid composition was determined for samples of chloroplast
      thylakoids isolated from Pisum sativum plants grown at light intensities of 50
      and 300 MUE.m(-2).s(-1) and from Aesculus hippocastanum leaves taken from shade
      or sun environments. Lighting conditions had no major effect on lipid class
      composition except for a small increase in the amount of
      monogalactosyldiacylglycerol relative to other lipids in low compared with high
      light and shade compared with sun conditions. The thylakoids from low light and
      shade environments also had, relative to those from high light and sun
      conditions, a substantial decrease in the level of trans-hexadecenoic acid in
      phosphatidyglycerol. In parallel with this there were lower lipid to chlorophyll
      ratios, higher overall fatty acid unsaturation, lower chlorophyll a to b ratios
      and increased relative levels of light harvesting chlorophyll a/b polypeptides as
      expected for an increase in the degree of thylakoid appression. With this in
      mind, our results on lipid class composition and content of trans-hexadecenoic
      acid are discussed in the context of the lateral distribution of lipids within
      the plane of membrane. 

PMID- 24443264
TI  - The activity of nitrate reductase and the pool sizes of some amino acids and some
      sugars in water-stressed maize leaves.
AB  - The activity of nitrate reductase and the pool sizes of some amino acids and some
      sugars were measured in relation to the leaf water potential (psi) of maize
      leaves. The activity of nitrate reductase was severely inhibited in water
      stressed maize leaves. This was not due to substrate shortage or the presence of
      an inhibitor at reduced leaf water potential. While the typical proteinogenic
      amino acids valine, tyrosine, leucine and isoleucine were almost undetectable in
      the leaves of the control plants, their concentrations markedly increased with
      declining psi, thus indicating protein degradation. The concentrations of serine,
      glycine and glutamate increased upon water stress, their total amount in severely
      stressed leaves ranging 5- to 6-fold higher than the total amount of valine,
      tyrosine, leucine and isoleucine at this stage of water deficit. The pool sizes
      of glucose, fructose and sucrose decreased in relation to decreasing psi. The
      total amount of organic solutes remained almost constant at least up to a psi of
      approx.-1.0 MPa and then dropped to about 50% when psi reached -1.25 MPa. 

PMID- 24443265
TI  - Influence of 2-(3,4 dichlorophenoxy)-triethylamine on photosynthesis of Phaseolus
      vulgaris L.
AB  - The effect of foliar sprays of the growth regulator 2-(3,4 dichlorophenoxy)
      triethylamine (DCPTA) on net photosynthesis (Pn) by intact bean plants depended
      upon concentration and the stage of development of the leaves. A single foliar
      spray of 2.0 mM DCPTA reduced Pn when applied to young expanding leaves but had
      little effect on fully expanded leaves. Lower DCPTA concentrations (0.2 to 0.8
      mM) had no effect on Pn, unless applied more than once which resulted in reduced
      Pn. The DCPTA-induced inhibition of Pn was associated with chlorosis and
      aberrations in chloroplast ultrastructure. DCPTA did not affect stomatal
      resistance. When applied to detached leaf disks in the dark, DCPTA retarded the
      normal loss of chlorophyll suggesting that DCPTA may have anti-seneseent
      properties. 

PMID- 24443266
TI  - Co-morbidity in persistent opioid users with chronic non-malignant pain in
      Norway.
AB  - BACKGROUND: In patients with chronic non-malignant pain (CNMP), co-morbid
      physical or mental health disorders are common and may have a negative impact on
      health-related quality of life and treatment outcomes. The purpose of this study
      was to examine the occurrence of chronic psychiatric and somatic diseases in
      persistent opioid users with CNMP compared with the general population in Norway.
      METHODS: In this cross-sectional study, prescription patterns of dispensed
      opioids were used to identify a study population of persistent opioid users with
      CNMP from the general population. Reimbursed prescriptions marked with diagnostic
      codes were used to identify the occurrence of 21 somatic and 3 psychiatric
      diseases for a 1-year period in the Norwegian Prescription Database. Occurrence
      of disease in persistent opioid users was compared to an age- and gender-specific
      population of all Norwegian residents aged 18-79 years in 2009. Standardized
      morbidity ratios (SMRs) for each disease were calculated. RESULTS: Eighty-five
      percent of the persistent opioid user population had at least one co-morbid
      disease compared with 45% of the general population. Forty-two percent had three
      or more co-morbidities. SMRs in both men and women were generally increased
      except for dementia, glaucoma and renal disease, indicating a higher occurrence
      of disease in persistent opioid users. CONCLUSIONS: A higher occurrence of both
      somatic and psychiatric co-morbidities in disease stages warranting
      pharmacological treatment was found in persistent opioid users with CNMP compared
      with the general population of Norway.

PMID- 24443267
TI  - Impaired osteogenic differentiation of mesenchymal stem cells derived from bone
      marrow of patients with lower-risk myelodysplastic syndromes.
AB  - The pathogenesis of myelodysplastic syndromes (MDS) has not been completely
      understood, and insufficiency of the hematopoietic microenvironment can be an
      important factor. Mesenchymal stem cells (MSCs) and osteoblasts are key
      components of the hematopoietic microenvironment. Here, we measured the
      expression of multiple osteogenic genes in 58 MSCs from MDS patients with
      different disease stages and subtypes by real-time PCR and compared the
      osteogenic differentiation of MSCs from 20 MDS patients with those of MSCs from
      eight normal controls quantitatively and dynamically. The mRNA level of Osterix
      and RUNX2, two key factors involved in the early differentiation process toward
      osteoblasts, was significantly reduced in undifferentiated MSCs from lower-risk
      MDS. After osteogenic induction, lower-risk MDS showed lower alkaline phosphatase
      activity, less intense alizarin red S staining, and lower gene expression of
      osteogenic differentiation markers; however, higher-risk MDS was normal. Finally,
      in bone marrow biopsy, the number of osteoblasts was significantly decreased in
      lower-risk MDS. These results indicate that MSCs from lower-risk MDS have
      impaired osteogenic differentiation functions, suggesting their insufficient
      stromal support in MDS. 

PMID- 24443268
TI  - Relationship of immunohistochemical biomarker expression and lymph node
      involvement in patients undergoing surgical treatment of NSCLC with long-term
      follow-up.
AB  - We try to identify the relationship between immunohistochemical marker expression
      and lymph node involvement in a cohort of 282 patients followed for 5 years after
      curative resection for NSCLC. In 189 patients (67%), lymph nodes were unaffected
      while 93 patients (33%) showed nodal involvement. The expression of 15 molecular
      markers was determined from each patient by tissue-array immunohistochemistry.
      Univariate analysis indicated significantly higher expression of E-cadherin,
      gamma-catenin, p27, and p53 in patients with lymph node involvement. In those
      with unaffected nodes, p16 and Rb were expressed. E-cadherin expression was
      related to a 50% mortality reduction in patients with node involvement (hazard
      ratio (HR) 0.5; p = 0.017). c-erbB-2 expression was correlated with a 3.4-fold
      increase in mortality compared to patients without expression of this marker in
      subjects without node involvement (HR 3.41; p = 0.017). Multivariate analysis
      identified c-erbB-2 (HR 2.22; p = 0.089) and p27 (HR 1.44; p = 0.019) as
      prognostics of mortality while Rb (HR 0.74) indicated a good prognosis. The
      expression of proteins encoded by oncogenes and tumor suppressor genes was
      different according to lymph node involvement. The increased mortality related to
      c-erbB-2 expression in patients with unaffected lymph nodes would suggests a need
      for adjuvant treatment.

PMID- 24443269
TI  - The effect of CYP1A1 and CYP1A2 polymorphisms on gastric cancer risk among
      different ethnicities: a systematic review and meta-analysis.
AB  - Potential Cytochrome P450s (CYPs) 1A1 MspI, 1A1 Ile462Val, 1A2*1 F, and/or 1A2*1C
      polymorphisms have been implicated in gastric cancer risk among different
      ethnicities. We aimed to explore the effect of CYP 1A1 MspI, 1A1 Ile462Val, 1A2*1
      F, and/or 1A2*1C polymorphisms on the susceptibility to gastric cancer among
      different ethnicities through a systematic review and meta-analysis. Each
      initially included article was scored for quality appraisal. Desirable data were
      extracted and registered into databases. A number of 11 studies were ultimately
      eligible for the meta-analysis of CYP1A1 MspI polymorphism, eight studies for the
      meta-analysis of 1A1 Ile462Val polymorphism, and two studies for the meta
      analysis of 1A2*1 F polymorphism. None of genetic model was evidently suggested,
      and thus all the genetic models were presented. Potential sources of
      heterogeneity were sought out via subgroup and sensitivity analyses, and
      publication biases were estimated. In our meta-analysis, significant results
      could be found in mutational heterozygous CT genotype, compared with wild TT
      genotype, among large sample size subgroup for CYP1A1 MspI polymorphism.
      Regarding CYP1A1 Ile462Val polymorphism, no statistically significant results
      could be found. For CYP1A2*1 F polymorphism, mutational heterozygous AC genotype,
      compared with wild-type AA, has deleterious effects, whereas mutational
      homozygous CC genotype, compared with mutational heterozygous type AC, has
      protective effects but lacks statistically significant difference despite its a
      proximity to 0.05. Combined mutational homozygous CC genotype and wild-type
      homozygous AA, compared with mutational heterozygous AC genotype, has protective
      effects. Our meta-analysis suggests no associations between CYP1A1 Ile462Val
      polymorphism and gastric cancer, but possible associations between CYP1A1 MspI
      and CYP1A2*1 F polymorphisms and gastric cancer, which needs to be further
      reinforced or refuted among different ethnicities in well-designed large-scale
      high-quality studies. 

PMID- 24443270
TI  - Efficacy of Cisplatin-loaded polybutyl cyanoacrylate nanoparticles on the
      glioblastoma.
AB  - Glioblastoma is known as one of the most aggressive human cancers. To gain access
      of the brain, therapeutic agents must overcome blood-brain barrier (BBB). In this
      study, Cisplatin (Cispt)-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs)
      were prepared through miniemulsion polymerization technique. They were coated
      with polysorbate 80 to cross the BBB of glioblastoma-bearing rats. Prepared NPs
      were characterized with respect to their size, size distribution, zeta potential,
      drug loading and encapsulation efficiency, cytotoxicity effects, drug release,
      and stability pattern. Size and zeta potential of nanodrug were found to be 489
      nm and -20 mV, while drug loading and encapsulation efficiency were determined to
      be 5% and 25%, respectively. Release studies demonstrated high retention
      capability of nanodrug in that 3.18% of Cispt was released from NPs in a period
      of 51 h. NPs presented acceptable stability after 2 months and lyophilization.
      Mean survival time in nanodrug receivers was 19.6 days, while it was 17.5 days
      for free drug receivers. Histological studies demonstrated efficacy of PBCA NPs
      in reducing side effects. Finally, such preparation can be considered as a
      promising nanocarrier for other types of tumor.

PMID- 24443271
TI  - A pyrimidopyrimidine Janus-AT nucleoside with improved base-pairing properties to
      both A and T within a DNA duplex: the stabilizing effect of a second endocyclic
      ring nitrogen.
AB  - Janus bases are heterocyclic nucleic acid base analogs that present two different
      faces able to simultaneously hydrogen bond to nucleosides that form Watson-Crick
      base pairs. The synthesis of a Janus-AT nucleotide analogue, (N)JAT , that has an
      additional endocyclic ring nitrogen and is thus more capable of efficiently
      discriminating T/A over G/C bases when base-pairing in a standard duplex-DNA
      context is described. Conversion to a phosphoramidite ultimately afforded
      incorporation into an oligonucleotide. In contrast to the first generation of
      carbocyclic Janus heterocycles, it remains in its unprotonated state at
      physiological pH and, therefore, forms very stable Watson-Crick base pairs with
      either A or T bases. Biophysical and computational methods indicate that (N)JAT
      is an improved candidate for sequence-specific genome targeting.

PMID- 24443272
TI  - The effects of PEG-based surface modification of PDMS microchannels on long-term
      hemocompatibility.
AB  - The current study demonstrates the first surface modification for
      poly(dimethylsiloxane) (PDMS) microfluidic networks that displays a long shelf
      life as well as extended hemocompatibility. Uncoated PDMS microchannel networks
      rapidly adsorb high levels of fibrinogen in blood contacting applications.
      Fibrinogen adsorption initiates platelet activation, and causes a rapid increase
      in pressure across microchannel networks, rendering them useless for long term
      applications. Here, we describe the modification of sealed PDMS microchannels
      using an oxygen plasma pretreatment and poly(ethylene glycol) grafting approach.
      We present results regarding the testing of the coated microchannels after
      extended periods of aging and blood exposure. Our PEG-grafted channels showed
      significantly reduced fibrinogen adsorption and platelet adhesion up to 28 days
      after application, highlighting the stability and functionality of the coating
      over time. Our coated microchannel networks also displayed a significant
      reduction in the coagulation response under whole blood flow. Further, pressure
      across coated microchannel networks took over 16 times longer to double than the
      uncoated controls. Collectively, our data implies the potential for a coating
      platform for microfluidic devices in many blood-contacting applications.

PMID- 24443274
TI  - Bronchiolar remodeling in adult mice following neonatal exposure to hyperoxia:
      relation to growth.
AB  - Preterm infants who receive supplemental oxygen for prolonged periods are at
      increased risk of impaired lung function later in life. This suggests that
      neonatal hyperoxia induces persistent changes in small conducting airways
      (bronchioles). Although the effects of neonatal hyperoxia on alveolarization are
      well documented, little is known about its effects on developing bronchioles. We
      hypothesized that neonatal hyperoxia would remodel the bronchiolar walls,
      contributing to altered lung function in adulthood. We studied three groups of
      mice (C57BL/6J) to postnatal day 56 (P56; adulthood) when they either underwent
      lung function testing or necropsy for histological analysis of the bronchiolar
      wall. One group inhaled 65% O2 from birth until P7, after which they breathed
      room air; this group experienced growth restriction (HE+GR group). We also used a
      group in which hyperoxia-induced GR was prevented by dam rotation (HE group). A
      control group inhaled room air from birth. At P56, the bronchiolar epithelium of
      HE mice contained fewer Clara cells and more ciliated cells, and the bronchiolar
      wall contained ~25% less collagen than controls; in HE+GR mice the bronchiolar
      walls had ~13% more collagen than controls. Male HE and HE+GR mice had
      significantly thicker bronchiolar epithelium than control males and altered lung
      function (HE males: greater dynamic compliance; HE+GR males: lower dynamic
      compliance). We conclude that neonatal hyperoxia remodels the bronchiolar wall
      and, in adult males, affects lung function, but effects are altered by
      concomitant growth restriction. Our findings may partly explain the reports of
      poor lung function in ex-preterm children and adults.

PMID- 24443273
TI  - Anemonin alleviates nerve injury after cerebral ischemia and reperfusion (i/r) in
      rats by improving antioxidant activities and inhibiting apoptosis pathway.
AB  - In the present study, we aimed at evaluating the potential neuroprotective effect
      and the underlying mechanism of anemonin against cerebral ischemia and
      reperfusion (I/R) injury. Anemonin was administered to rats by the
      intraperitoneally (i.p.) route once daily for 7 days before middle cerebral
      artery occlusion (MCAO). Focal cerebral ischemia was induced by 90 min of MCAO
      followed by 24 h of reperfusion. After that, animals were sacrificed by
      decapitation, brain was removed, and various biochemical estimations,
      neurological status, and assessment of cerebral infarct size were carried out.
      MCAO followed by 24 h of reperfusion caused a significant increase in infarct
      size, neurological deficit score, malondialdehyde (MDA) content, reactive oxygen
      species (ROS) level, and DNA fragmentation, as well as a decrease in the
      activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione
      (GSH), glutathione peroxidase (GPx), and Na(+), K(+)-ATPase in the brain.
      Furthermore, elevated Bax expression, increased caspase-3 cleavage, and decreased
      Bcl-2 expression were observed in nontreated rats in response to focal cerebral
      I/R injury. However, pretreatment with anemonin significantly reversed these
      levels of biochemical parameters, reduced cerebral infarct size, and improved the
      neurologic score in cerebral ischemic animals. Additionally, a wide distribution
      of anemonin in plasma and brain tissues and the brain-to-plasma partition
      coefficient (Ri) ratio of 0.7 at 90 min indicated that this compound could
      penetrate the blood-brain barrier (BBB). These results showed that pretreatment
      with anemonin provided a significant protection against cerebral I/R injury in
      rats by, at least in part, its antioxidant action and consequent inhibition of
      apoptosis. 

PMID- 24443275
TI  - Insomnia in paediatric chronic pain and its impact on depression and functional
      disability.
AB  - BACKGROUND: Children and adolescents attending health care due to chronic pain
      commonly presents with insomnia. Previous research suggests that problems with
      sleep are associated with depression and functional disability. However, more
      research is needed to clarify the relationship between pain, insomnia and
      disability. OBJECTIVE: This study aims to investigate the frequency, severity and
      importance of insomnia in paediatric patients with chronic pain and to evaluate
      the mediating role of insomnia in explaining the relationship between pain and
      depression as well as between pain and functioning. In addition, to ascertain the
      adequacy of using a Swedish translation of the Insomnia Severity Index (ISI) with
      youths, analyses included a statistical evaluation of the instrument. METHOD:
      Correlational analyses of cross-sectional data from 154 consecutive paediatric
      patients with chronic pain referred to a tertiary pain clinic. RESULTS: Insomnia
      explained a significant amount of variance in depression and functional
      disability when controlling for demographic characteristics and pain. Indirect
      effects of insomnia were found for both the relationship between pain and
      depression, and between pain and functional disability. ISI showed satisfactory
      psychometric properties in this sample, including internal consistency and
      concurrent criteria validity. CONCLUSIONS: Insomnia is highly important in
      explaining depression and functional disability in paediatric chronic pain and
      can be adequately assessed using the ISI.

PMID- 24443276
TI  - Mandibular condyle erosion and sclerosis in pediatric patients treated with
      radiotherapy to the head and neck region.
AB  - Head and neck radiotherapy in children is associated with significant acute and
      late morbidities. Temporomandibular joint dysfunction and trismus has been widely
      reported in patients receiving radiotherapy for sarcomas and nasopharyngeal
      carcinoma; however, erosion of the mandibular condyle is a rare sequela of modern
      radiotherapy techniques. In this report, we present three cases of erosion of the
      temporomandibular joint amongst pediatric patients treated with radiotherapy for
      distinct head, neck and brain malignancies.

PMID- 24443278
TI  - A value-added methodology for assessing the effectiveness of psychiatric
      residency training.
AB  - Educators often find it difficult to identify variables that accurately assess
      the knowledge that residents have gained due to their training. Recently in
      professional education circles, attention has shifted from process to outcome
      variables, with more emphasis being placed on student gains rather than on
      program resources. A methodology used extensively to assess undergraduate
      education is the value-added approach. This methodology is often demonstrated by
      a change in scores from two administrations of a test instrument that measures
      students' specific knowledge or aptitudes. Residency training programs that offer
      standardized examinations to their residents are in a good position to utilize
      this evaluation technique. This article will demonstrate how the value-added
      technique can be used to demonstrate cognitive growth in psychiatric residents by
      using the Psychiatry Resident In-Training Examination. 

PMID- 24443277
TI  - Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic
      leukemia, follicular lymphoma, and rheumatoid arthritis.
AB  - Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment
      of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous
      ofatumumab were characterized in patients with relapsed/refractory chronic
      lymphocytic leukemia, relapsed/refractory follicular lymphoma, and rheumatoid
      arthritis, diseases with widely varying CD20+ B-cell counts in blood. Serum
      concentration data from a total of 477 patients who received ofatumumab doses
      ranging from 100 mg to 2000 mg in different dosing regimens were analyzed to
      determine the pharmacokinetic characteristics of ofatumumab across different
      patient groups and to identify factors contributing to the pharmacokinetic
      variability. Ofatumumab pharmacokinetics were well described by a linear two
      compartment model component to represent non-specific monoclonal antibody
      clearance from the central compartment interacting with a model component
      representing the target-mediated clearance of ofatumumab by binding to CD20
      expressed on B cells. The clearance (7.5 mL/h) and steady-state volume of
      distribution (5.3 L) for the linear, non-specific component were consistent with
      results obtained for other monoclonal antibodies. The target-mediated clearance
      component was related to the disease-specific number of circulating B cells,
      which will allow simulation of the contribution of target-mediated clearance to
      ofatumumab pharmacokinetics in untested disease states with data on B-cell counts
      and turnover.

PMID- 24443279
TI  - Residency training in emergency psychiatry : changes between 1980 and 1990.
AB  - Independent random samples of residency training programs were surveyed in 1980
      and in 1990 about their emergency psychiatry training. A larger percentage of the
      programs required daytime emergency service duty in 1990 (80%), compared with
      1980 data (50%), and a larger percentage offered a daytime block training
      rotation, defined as at least 5 days a week of emergency psychiatry for at least
      4 weeks (48%), compared with 23% in 1980. Each sample reported that the most
      important topics in emergency psychiatry were being taught. In 1990, two trends
      were noted: 1) more faculty psychiatrist time allocated to the emergency service,
      and 2) more emergency patient visits per shift. In 1990, the residents said they
      felt more stressed by the heavy patient load and lack of disposition facilities
      than in 1980, but less stressed by the lack of faculty interest and backup. Based
      on the data, the interpretation was made that emergency psychiatry training had
      improved over this period; however, it was indicated that further improvement was
      also needed. 

PMID- 24443280
TI  - Emergency psychiatry training and the decision to hospitalize : a longitudinal
      study of psychiatric residents.
AB  - To assess the impact of a 6-month emergency psychiatry training program on
      emergency psychiatric decision making, we studied 577 emergency psychiatric
      patient evaluations conducted by 15 first-year psychiatry residents. By their
      fifth month of training, the residents' rates of emergency patient
      hospitalization declined from 33% to 19%. For residents in the early training
      phase, various clinical features, including psychosis, thought disorder,
      schizophrenic diagnosis, dangerousness, and overall symptoms, were associated
      with higher rates of patient hospitalization. By the end of training, only
      dangerousness and overall symptoms remained significantly related to the
      hospitalization decision. Specific training in emergency psychiatry may affect
      psychiatric decision-making practices as early as the first year of residency
      training. 

PMID- 24443281
TI  - Child and adolescent psychiatry in third-year psychiatry clerkships.
AB  - The 1991-1992 Directors of Medical Student Education in Psychiatry were surveyed
      to investigate the exposure of undergraduate medical students in the United
      States to child and adolescent psychiatry during the psychiatry clinical
      clerkship. The response rate was 100% (N = 122). Forty-four (36.1%) medical
      schools provided no exposure to child and adolescent psychiatry patients during
      the psychiatry clerkship. Sixty-one (50%) medical schools provided inpatient
      experience for their students in child and adolescent psychiatry, although only
      24.2% of students in the clerkships were assigned to these units. Seventeen
      (13.9%) medical schools provided outpatient or consultation-liaison experience in
      child and adolescent psychiatry for students. These results demonstrate the lack
      of exposure to child and adolescent psychiatry for the majority of medical
      students during psychiatry clerkships. The medical school curriculum has a
      significant effect on specialty selection. The introduction of an undergraduate
      medical education curriculum that includes child and adolescent psychiatry may
      address the severe shortage of child and adolescent psychiatrists to provide for
      patient care, academic, and research needs. Proposals are made to facilitate
      implementation of child and adolescent psychiatry into the undergraduate medical
      curriculum. 

PMID- 24443282
TI  - Palmtop computer residency log.
AB  - This pilot study explored the usefulness of portable electronic organizers
      (palmtop computers) to log residents' clinical activity. Nine residents were
      randomly assigned palmtops, 18 continued using a nonautomated system (paper log).
      After 8 months, resident compliance, frequency of data entry, and submission of
      log data were better in the palmtop group. Data are easily transferred from the
      palmtop to a desktop computer data base to generate reports. Start-up costs are
      comparable to other automated systems, and ongoing costs are minimal. The palmtop
      log appears to be a viable alternative to the paper log. 

PMID- 24443283
TI  - The economics of survival for academic psychiatry.

PMID- 24443286
TI  - The dilemma of unavailable videotapes for psychiatric education.

PMID- 24443284
TI  - Frequently asked questions about medical student education in psychiatry.

PMID- 24443287
TI  - A hierarchical finite mixture model that accommodates zero-inflated counts, non
      independence, and heterogeneity.
AB  - A number of mixture modeling approaches assume both normality and independent
      observations. However, these two assumptions are at odds with the reality of many
      data sets, which are often characterized by an abundance of zero-valued or highly
      skewed observations as well as observations from biologically related (i.e., non
      independent) subjects. We present here a finite mixture model with a zero
      inflated Poisson regression component that may be applied to both types of data.
      This flexible approach allows the use of covariates to model both the Poisson
      mean and rate of zero inflation and can incorporate random effects to accommodate
      non-independent observations. We demonstrate the utility of this approach by
      applying these models to a candidate endophenotype for schizophrenia, but the
      same methods are applicable to other types of data characterized by zero
      inflation and non-independence.

PMID- 24443288
TI  - Outcome of chronic isolated anterior cruciate ligament reconstruction.
AB  - The aim of the article is to identify demographic and intraoperative factors that
      predict patient-oriented outcomes as measured by knee-specific and general
      quality of life (QoL) questionnaires for chronic, unilateral primary anterior
      cruciate ligament (ACL) tears following surgical reconstruction. A total of 69
      patients were prospectively evaluated using the Medical Outcomes Study 36-item
      Short Form (SF-36), modified Lysholm, Tegner activity level, and subjective
      portion of the International Knee Documentation Committee (IKDC) questionnaires.
      The surveys were administered preoperatively and postoperatively with a minimum 2
      year follow up. Efficacy of treatment was evaluated by comparing preoperative and
      postoperative questionnaire scores. Multivariate linear regression analysis was
      used to identify demographic and intraoperative variables that were independent
      predictors of outcome. At a minimum 2-year follow-up (mean, 3.6 years), 55 of 69
      patients (80%) were available for follow-up. There were statistically significant
      improvements in the Lysholm, Tegner, and subjective portion of the IKDC, as well
      as several SF-36 domains that measure physical capabilities (p < 0.001) .
      Increasingly, severe patellofemoral and medial compartment articular cartilage
      damage was associated with lower physical function (PF) (p = 0.009 and 0.005,
      respectively) and physical component (p = 0.041 and 0.033, respectively) scores
      on the SF-36. Medial compartment articular cartilage damage and the presence of a
      lateral meniscus tear were independent predictors of lower bodily pain (BP)
      scores on the SF-36 (p = 0.007 and 0.010, respectively). QoL and knee function
      were improved following ACL reconstruction for chronic ACL tears. Independent
      predictors of poorer outcome were identified in the PF, bodily pain, and physical
      component score (PCS) of the SF-36. Increasingly, severe articular cartilage
      injury to the medial and patellofemoral compartments, as well as the presence of
      a lateral meniscal tear were predictive of poorer outcomes. 

PMID- 24443289
TI  - Supramolecular approaches towards ordered polymer materials.
AB  - Controlled organization of polymer chains into ordered structures is highly
      important to tune or enhance the properties of the polymeric materials. A
      supramolecular approach using host-guest chemistry has allowed rational design of
      chain assemblies with many functional properties. Nanoporous materials with
      ordered channel structures are particularly useful for attaining precise
      assemblies of polymer chains through nanoconfinement. 

PMID- 24443290
TI  - Tracheal reconstruction using chondrocytes seeded on a poly(L-lactic-co-glycolic
      acid)-fibrin/hyaluronan.
AB  - Reconstruction of trachea is still a clinical dilemma. Tissue engineering is a
      recent and promising concept to resolve this problem. This study evaluated the
      feasibility of allogeneic chondrocytes cultured with fibrin/hyaluronic acid (HA)
      hydrogel and degradable porous poly(L-lactic-co-glycolic acid) (PLGA) scaffold
      for partial tracheal reconstruction. Chondrocytes from rabbit articular cartilage
      were expanded and cultured with fibrin/HA hydrogel and injected into a 5 * 10 mm
      sized, curved patch-shape PLGA scaffold. After 4 weeks in vitro culture, the
      scaffold was implanted on a tracheal defect in eight rabbits. Six and 10 weeks
      postoperatively, the implanted sites were evaluated by bronchoscope and
      radiologic and histologic analyses. Ciliary beat frequency (CBF) of regenerated
      epithelium was also evaluated. None of the eight rabbits showed any sign of
      respiratory distress. Bronchoscopic examination did not reveal stenosis of the
      reconstructed trachea and the defects were completely recovered with respiratory
      epithelium. Computed tomography scan showed good luminal contour of trachea.
      Histologic data showed that the implanted chondrocytes successfully formed
      neocartilage with minimal granulation tissue. CBF of regenerated epithelium was
      similar to that of normal epithelium. Partial tracheal defect was successfully
      reconstructed anatomically and functionally using allogeneic chondrocytes
      cultured with PLGA-fibrin/HA composite scaffold.

PMID- 24443291
TI  - Narcissistic biographies--third age self-transcendence abilities.
AB  - Narcissistic traits interfere in the process of self-determination and the
      individual motivational strategies of human beings. The grandiose and vulnerable
      narcissistic personality subtypes have difficulties in their education,
      interpersonal relationships and quality of life. The latter is also affected by
      ageing, whose attributes influence, above all, one's self-esteem, especially in
      women. Though very fearful of suffering and death, narcissists have a powerful
      desire to overcome them by cultivating their grandiosity, especially through the
      mystical and paranormal experiences they relate. The spiritual means of
      transcending one's self, including the components of magical thinking, can
      prevent the destruction of self-esteem in narcissists in their third-age.

PMID- 24443292
TI  - Routine drug and food interactions during antihelminthic treatment of
      neurocysticercosis: a reason for the variable efficacy of albendazole and
      praziquantel?
AB  - Neurocysticercosis (NC) or infection of the central nervous system with Taenia
      solium larvae is a leading cause of preventable seizures and epilepsy in endemic
      regions across the globe. Albendazole and praziquantel are commonly used
      antihelminthic agents to treat NC; however, viable cysts persist in the majority
      of patients, putting them at risk for future seizures and other neurological
      complications. Because of their pharmacokinetic profiles, albendazole and
      praziquantel have the potential to interact with many different drugs. During
      antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co
      administered to manage seizures and cerebral edema; however, the most commonly
      used agents from these drug classes are known to significantly alter plasma
      concentrations of albendazole and praziquantel. The overarching issue with drug
      interactions during the treatment of NC is whether or not they have clinical
      relevance, as the plasma concentrations of albendazole and praziquantel have not
      been directly linked with eradication of viable cysts. Future studies should
      attempt to evaluate the validity of a causal relationship between antihelminthic
      plasma concentrations and outcomes so that drug interactions can be better
      understood and managed and so that treatment can be optimized. 

PMID- 24443293
TI  - Heterotopic and homotopic nociceptive conditioning stimulation: distinct effects
      of pain modulation.
AB  - BACKGROUND: Within an area, habituation and sensitization represent well
      established modulatory effects to repetitive noxious input. Less is known
      regarding the nociceptive conditioning effects between body sites - i.e., how
      stimulating one site may affect another. Therefore, we investigated the effects
      of nociceptive stimulation of anatomically distinct locations (shoulder and hand)
      on pain rating and evoked potentials (i.e., contact heat-evoked potentials).
      METHODS: The effect of stimulation order was assessed in eight healthy subjects.
      The shoulder was examined before the hand or the hand before the shoulder. All
      subjects underwent both conditions (shoulder before hand and hand before
      shoulder) on separate days. In an additional 30 subjects (total n = 38), between
      retesting the shoulder or the hand, conditioning stimulation in the respective
      other location (i.e., hand or shoulder) was applied. Both analyses focused upon
      changes in the magnitude of evoked pain responses in relation to the respective
      area being conditioned by heterotopic stimulation. RESULTS: When the shoulder was
      stimulated before the hand, N2P2 amplitude was significantly reduced. In
      contrast, stimulating the hand before the shoulder resulted in significant
      response increments (shorter N2 latency). Additionally, conditioning stimulation
      of the hand resulted in increased pain rating to shoulder stimulation.
      CONCLUSIONS: Overall, these findings indicate that response modulation to noxious
      contact heat stimulation depends upon conditioning stimulus location. These
      effects represent changes beyond conventional habituation due to repeated
      stimulation in the same area.

PMID- 24443294
TI  - A curriculum for learning in psychiatric residencies about homosexuality, gay
      men, and lesbians.
AB  - Homosexuality was redefined by the American Psychiatric Association in 1973 as a
      variation in sexual orientation rather than a mental illness, and recent research
      has greatly expanded knowledge about homosexuality, gay men, and lesbians.
      However, generally speaking, neither a non pathological perspective nor this new
      information has been integrated into psychiatric residency curricula. This
      absence compromises the ability of residency programs to train residents to be
      broadly competent in dealing with issues related to these topics. Learning about
      homosexuality, gay men, and lesbians should be integrated into all psychiatric
      residencies, and a curriculum to serve as a basic model for this necessary
      professional training is proposed. 

PMID- 24443295
TI  - The skewing of psychiatry.
AB  - Two of the most influential factors in psychiatry over the past decade have been
      the increasing availability of more sophisticated psychotropic medication and the
      widespread acceptance of DSM-III. These factors, along with the increased use of
      computers, have dramatically skewed the field toward an atheoretic
      symptom/syndrome orientation and away from an appreciation that meaning is an
      indispensable aspect of human life. This threatens to lead to a serious
      deterioration in our capacity to communicate with, understand, and treat people.
      In championing the notion that "biology drives psychology," psychiatry must not
      lose sight of the fact that often "psychology drives biology." Modest training
      proposals are offered to counterbalance these trends. 

PMID- 24443296
TI  - Psychiatric residency directors' use of computers in their training programs.
AB  - Over 73% (169) of psychiatric residency training directors who responded to a
      survey believe that computer instruction should be provided to residents. The
      survey instrument, a questionnaire, was mailed to residency directors of general
      and child psychiatry programs (N = 314) in 1991. The authors found that computers
      are available for resident use in 165 (79%) programs, but only 87 (38%) residency
      programs provide computer instruction for their trainees. Over 85% (182) of the
      directors have used computers, with 45% (90) of them using computers at least 3
      hours per week. The directors' own use of computers is strongly associated with
      typing skill level and familiarity with different software packages. There is a
      discrepancy between the amount of computer instruction provided for residents and
      the amount the directors desire. The authors also found that most directors are
      not familiar with software packages developed specifically for psychiatrists that
      are now available. 

PMID- 24443297
TI  - What Are We Training For? : A Follow-up Survey of a Child Psychiatry Training
      Program.
AB  - The authors report the results of a 1990 survey of 91 graduates of the 2-year
      training program in child psychiatry at the University of Toronto. The
      participants, who completed their training between 1982 and 1989, completed a
      structured questionnaire designed to assess current patterns of practice,
      consultation, and academic activities. The respondents were also asked which
      aspects of their training were relevant to their current practice and what topics
      would be of interest for continuing medical education. The implications of the
      results for planning child psychiatry training curricula are discussed. (Academic
      Psychiatry 1994; 18:88-94). 

PMID- 24443298
TI  - Future career choices of women psychiatric residents : is research included?
AB  - In an attempt to understand the paucity of women in psychiatric research, a
      descriptive pilot survey of women psychiatry residents in three residency
      programs was undertaken in 1992 to investigate the factors that influenced career
      choice and interest in research. Only 5% of the respondents intended to pursue an
      academic career with an emphasis on research; 60% listed a research career as
      their last choice. Significant factors that affect professional training and
      subsequent career choice included the women's desire for a nurturing training
      environment, availability of mentors/role models, and personal and family
      considerations. 

PMID- 24443299
TI  - Gender differences in career paths in psychiatry.

PMID- 24443302
TI  - Video biographies of jung and erickson : teacher guidance is important for
      classroom use.

PMID- 24443300
TI  - Frequently asked questions about training in psychoanalysis.

PMID- 24443303
TI  - Outcome of children treated for relapsed acute myeloid leukemia in Central
      America.
AB  - BACKGROUND: Relapsed childhood acute myeloid leukemia (AML) outcomes have not
      been documented in resource-limited settings. We examined survival after relapse
      for children with AML (non-APML) and acute promyelocytic leukemia (APML) in
      Central America. PROCEDURE: We retrospectively evaluated outcomes of children
      with first relapse of AML (non-APML) and APML in Guatemala, Honduras, or El
      Salvador diagnosed between 1997 and 2011. Predictors of subsequent event-free
      survival (EFS) and overall survival (OS) were examined. RESULTS: We identified
      140 children with relapsed AML (non-APML), and 24 with relapsed APML. Two-year
      subsequent EFS and OS (+/-SE) were 7.0 +/- 2.5% and 9.1 +/- 2.8%, respectively.
      Worse outcomes were associated with Hispanic or Indigenous heritage, white blood
      cell count at diagnosis >=50 * 10(9) /L, and time to relapse <18 months. For
      those with relapsed APML, subsequent 2-year EFS and OS were 36.7 +/- 10.8% and
      43.4 +/- 12.1%, although few patients survived beyond 3 years. 15.2% of all
      patients were managed solely with palliative intent following first relapse.
      CONCLUSIONS: Children with relapsed AML in Central America rarely survive, so
      palliative strategies should be considered following relapse in this population.
      However, children with late relapse or with APML may have a prolonged period of
      remission with second treatment, and consideration of re-treatment may be
      appropriate.

PMID- 24443304
TI  - Social support and anxiety levels of parents with disabled children.
AB  - PURPOSE: This is a descriptive study carried out to determine the state-trait
      anxiety and social support perceptions of parents with disabled children.
      DESIGN/METHODS: This study has been carried out on 75 parents whose children
      attended the Private Rehabilitation Center. The data included the personal
      information form composed by the investigators, the state-trait anxiety
      inventory, and the multi-dimensional scale of perceived social support. FINDINGS:
      The disabilities of the children were mental in 26.7%, physical in 25.3%, and
      physical/mental in 12%. As the degree of disability increased and the income
      levels decreased, the trait anxiety scores of the parents increased. There was a
      significant negative correlation between parental age and social support. Among
      the parents, 37.3% experienced problems with their spouses after having a child
      with a disability. CONCLUSIONS: The development and implementation of alternative
      support systems for of parents with disabled children would be beneficial.

PMID- 24443305
TI  - Development of a simple chromatographic method for the determination of piracetam
      in human plasma and its pharmacokinetic evaluation.
AB  - OBJECTIVE: The objective of study was to develop an accurate and reproducible
      HPLC method for determination of piracetam in human plasma and to evaluate
      pharmacokinetic parameters of 800 mg piracetam. METHODS: A simple, rapid,
      accurate, precise and sensitive high pressure liquid chromatography method has
      been developed and subsequently validated for determination of piracetam. This
      study represents the results of a randomized, single-dose and single-period in 18
      healthy male volunteers to assess pharmacokinetic parameters of 800 mg piracetam
      tablets. Various pharmacokinetic parameters were determined from plasma for
      piracetam and found to be in good agreement with previous reported values. The
      data was analyzed by using Kinetica(r) version 4.4 according to non-compartment
      model of pharmacokinetic analysis and after comparison with previous studies, no
      significant differences were found in present study of tested product. RESULTS:
      The major pharmacokinetic parameters for piracetam were as follows: t1/2 was
      (4.40 +/- 0.179) h; Tmax value was (2.33 +/- 0.105) h; Cmax was (14.53 +/- 0.282)
      ug/mL; the AUC(0-infinity) was (59.19 +/- 4.402) ug . h/mL. AUMC(0-infinity) was
      (367.23 +/- 38.96) ug. (h)(2)/mL; Ke was (0.16 +/- 0.006) h; MRT was (5.80 +/-
      0.227) h; Vd was (96.36 +/- 8.917 L). CONCLUSIONS: A rapid, accurate and precise
      high pressure liquid chromatography method was developed and validated before the
      study. It is concluded that this method is very useful for the analysis of
      pharmacokinetic parameters, in human plasma and assured the safety and efficacy
      of piracetam, can be effectively used in medical practice.

PMID- 24443306
TI  - Effects of LDL and oxidized LDL on cardiac function in isoproterenol-induced
      myocardial infarction in rat.
AB  - Notable discussions have been developed over the distinctive effects of LDL and
      oxidized LDL (OxLDL) on myocardial functions. The aim of the present study was to
      investigate the effects of OxLDL on electrocardiogram and hemodynamic parameters
      of rat's heart in isoproterenol (ISO)-induced myocardial infarction (MI)
      model.Male Wistar rats were allocated in to 6 groups and receive one of the 3
      formulated diets (standard, cholesterol-rich and oxidized cholesterol-rich
      diets). After 14 weeks to induce MI, rats in 3 groups were received ISO (100
      mg/kg) for 2 consecutive days subcutaneously. Lipid profiles, electrocardiogram
      patterns and hemodynamic parameters of all groups were investigated.Serum levels
      of LDL, cholesterol and triglycerides were significantly higher in the fat-rich
      diet fed groups compared to control group (P<0.001). The ISO-treated rats showed
      a marked reduction in the R-amplitude, R-R interval, LVSP, left ventricular
      contractility (LVdP/dtmax) and relaxation (LVdP/dtmin) as well as severe
      elevation in ST-segment and LVEDP value compared to the respective normal rats.
      High serum level of OxLDL resulted in significant exacerbation in the destructive
      effects of ISO on R-amplitude, R-R interval, LVSP, left ventricular contractility
      (LVdP/dtmax), relaxation (LVdP/dtmin), ST-segment and LVEDP values. Additionally,
      heart to body weight ratio as an index of myocardial edematous was also increased
      significantly. However, changes in these parameters in rats fed with cholesterol
      rich diet were not significant.Generally, results indicated that the effects of
      high OxLDL level on electrocardiogram and hemodynamic parameter after MI was more
      reliable than effects of high LDL level. 

PMID- 24443307
TI  - Freeze-dried amorphous dispersions for solubility enhancement of thermosensitive
      API having low molecular lipophilicity.
AB  - The present study focuses on the development of an alternative 'thermally gentle'
      strategy such as freeze-drying to obtain not only solubility enhanced but also
      physically stabilised amorphous solid dispersions of acetazolamide, which melt
      with decomposition (M.P.~260 degrees C). The solid dispersions were prepared by
      freeze-drying an aqueous dispersion of acetazolamide containing a lyoprotectant
      as sugar alcohol (mannitol) in 1:0.5, 1:1 and 1:2 proportions by weight. All the
      proportions of solid dispersions reported a marked increase in solubility
      characteristics compared to those of pure drug; with outstanding performance by
      1:1 ratio of about 6 folds rise in saturation solubility and 90% drug release in
      about initial 30 minutes. This could be attributed to the formation amorphous
      molecular dispersions, cosolvent effect of mannitol on dispersed acetazolamide as
      well as its local solubilisation effect at the diffusion layer. During stability
      study also, 1:1 ratio of solid dispersions reported an insignificant change in
      solubility characteristics subjected to an unchanged amorphous nature. Such
      physical stability could be attributed to decreased molecular mobility of the
      drug molecules in amorphous carrier because of weaker drug-carrier interactions.
      Thus, it was demonstrated that freeze-drying is an effective method of forming
      dissolution-enhanced, amorphous solid dispersions of thermally degradable APIs.

PMID- 24443308
TI  - Development and validation of a simple and reliable LC-MS/MS method for the
      determination of acetazolamide, an effective carbonic anhydrase inhibitor, in
      plasma and its application to a pharmacokinetic study.
AB  - A simple, rapid and accurate liquid chromatography - tandem mass spectrometry
      method was developed and validated for the quantification of acetazolamide in
      beagle plasma using sulfadiazine as the internal standard. After extraction by
      acetonitrile, the analytes were separated by a rapid gradient elution with
      acetonitrile and water as the mobile phase on a SHIMADZU VP-ODS C18 column and
      then detected by an API 4000 triple-quadrupole mass spectrometer using
      electrospray ionization in negative ion mode. Multiple reaction monitoring was
      performed on the ion transitions of m/z 220.9->83.3 (acetazolamide) and m/z 248.9
      >185.0 (sulfadiazine). The plasma concentration of acetazolamide in beagle dogs
      showed good linearity over the range of 0.20~50 MUg/mL, and the intra- and inter
      day variations were small with high accuracy and absolute recovery. Both analytes
      can maintain stable during the whole experimental process. The developed method
      was successfully applied to the pharmacokinetic study of acetazolamide extended
      release capsules after oral administration to beagle dogs.

PMID- 24443309
TI  - A targeting drug delivery system for ovarian carcinoma: transferrin modified
      lipid coated paclitaxel-loaded nanoparticles.
AB  - The transferring modified lipid coated PLGA nanoparticles, as a targetable
      vector, were developed for the targeting delivery of anticancer drugs with
      paclitaxel (PTX) as a model drug to the ovarian carcinoma, which combines the
      advantages and avoids disadvantages of polymeric nanoparticles and liposomes in
      drug delivery. A transmission electron microscopy (TEM) confirmed the lipid
      coating on the polymeric core. Physicochemical characterizations of TFLPs, such
      as particle size, zeta potential, morphology, encapsulation efficiency, and in
      vitro PTX release, were also evaluated. In the cellular uptake study, the TFLPs
      were more efficiently endocytosed by the A2780 cells with high expression of
      transferrin receptors than HUVEC cells without the transferrin receptors.
      Furthermore, the anticancer efficacy of TFLPs on the tumor spheroids was stronger
      than that of lipid coated PLGA nanoparticles (LPs) and PLGA nanoparticles. In the
      in vivo study, the TFLPs showed the best inhibition effect of the tumor growth
      for the ovarian carcinoma-bearing mice. In brief, the TFLPs were proved to be an
      efficient targeting drug delivery system for ovarian carcinoma. 

PMID- 24443310
TI  - An integrated teaching method of gross anatomy and computed tomography radiology.
AB  - It is essential for medical students to learn and comprehend human anatomy in
      three dimensions (3D). With this in mind, a new system was designed in order to
      integrate anatomical dissections with diagnostic computed tomography (CT)
      radiology. Cadavers were scanned by CT scanners, and students then consulted the
      postmortem CT images during cadaver dissection to gain a better understanding of
      3D human anatomy and diagnostic radiology. Students used handheld digital imaging
      and communications in medicine viewers at the bench-side (OsiriX on iPod touch or
      iPad), which enabled "pixel-to-tissue" direct comparisons of CT images and
      cadavers. Students had lectures and workshops on diagnostic radiology, and they
      completed study assignments where they discussed findings in the anatomy
      laboratory compared with CT radiology findings. This teaching method for gross
      and radiological anatomy was used beginning in 2009, and it yielded strongly
      positive student perspectives and significant improvements in radiology skills in
      later clinical courses.

PMID- 24443311
TI  - Survey Regarding Provisions of a 3-Day Supply of an Antihypertensive.
AB  - OBJECTIVE: To evaluate the provisions made by pharmacists when dispensing an
      emergency supply of an antihypertensive medication to patients in a community
      setting. PARTICIPANTS: Pharmacists and nonpharmacists (pharmacy technicians or
      interns) who were employed with community pharmacies and have witnessed or
      dispensed an emergency supply of an antihypertensive medication. Those who agreed
      to participate in this study via informed consent. INTERVENTION: A short
      questionnaire was used to assess the provisions made by community pharmacists
      from the perspectives of both the pharmacists and the nonpharmacists. MAIN
      OUTCOME MEASURES: Availability of blood pressure machines, evaluation of blood
      pressure readings, and patient counseling sessions or assessments prior to
      dispensing the emergency supply of an antihypertensive were the major outcome
      measures. RESULTS: Among the participants, 92% of the pharmacists and 79% of the
      nonpharmacists reported they have witnessed or dispensed an emergency supply of
      an antihypertensive medication. Of those, 82% of the pharmacists and 78% of the
      nonpharmacists recognized there were blood pressure machines available. However,
      78% of the pharmacists and 72% of the nonpharmacists acknowledged the patient's
      blood pressure was not checked. CONCLUSION/IMPLICATION: This observational study
      demonstrates that provisions when dispensing an emergency supply of an
      antihypertensive medication are inconsistent. Further evaluation is warranted.

PMID- 24443313
TI  - A Research Elective Course on Dietary Supplements to Engage Doctor of Pharmacy
      Students in Primary Literature Evaluation and Scholarly Activity.
AB  - PURPOSE: To develop and implement a research elective course to enhance skills of
      pharmacy students on primary literature evaluation and evidence-based practice on
      dietary supplements and generate scholarly publications. METHODS: A 2 credit hour
      independent research elective course was designed and implemented in the third
      year doctor of pharmacy curriculum. The course involved student-led research
      activities that included formulating research project, reviewing of primary
      literature, collection and evaluation of data, and writing of review articles for
      publication in peer-reviewed journals. An online survey was administered to
      evaluate students' perceptions of the course. RESULTS: Students successfully
      completed the course. The course resulted in peer-reviewed publications through
      student-faculty collaboration. Pharmacy students enrolled in the elective course
      perceived that the course helped them enhance their analytical reasoning,
      critical thinking and drug-literature evaluation skills, gain evidence-based
      knowledge, and apply the knowledge into practice during their advanced pharmacy
      practice experiences community pharmacy rotations. CONCLUSIONS: The course
      provided opportunity to the pharmacy students to not only critically search and
      evaluate the literature but also publish in peer-reviewed journals. Other
      pharmacy schools/colleges can adopt this course model to create opportunities for
      student-faculty collaborations toward scholarly accomplishments.

PMID- 24443316
TI  - Enzyme design from the bottom up: an active nickel electrocatalyst with a
      structured peptide outer coordination sphere.
AB  - Catalytic, peptide-containing metal complexes with a well-defined peptide
      structure have the potential to enhance molecular catalysts through an enzyme
      like outer coordination sphere. Here, we report the synthesis and
      characterization of an active, peptide-based metal complex built upon the well
      characterized hydrogen production catalyst [Ni(P(Ph)2N(Ph))2](2+)
      (P(Ph)2N(Ph)=1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane). The incorporated
      peptide maintains its beta-hairpin structure when appended to the metal core, and
      the electrocatalytic activity of the peptide-based metal complex (~100,000 s(-1))
      is enhanced compared to the parent complex ([Ni(P(Ph)2N(APPA))2](2+); ~50,500 s(
      1)). The combination of an active molecular catalyst with a structured peptide
      provides a scaffold that permits the incorporation of features of an enzyme-like
      outer-coordination sphere necessary to create molecular electrocatalysts with
      enhanced functionality.

PMID- 24443317
TI  - Changing resident test ordering behavior: a multilevel intervention to decrease
      laboratory utilization at an academic medical center.
AB  - Hospital laboratory test volume is increasing, and overutilization contributes to
      errors and costs. Efforts to reduce laboratory utilization have targeted aspects
      of ordering behavior, but few have utilized a multilevel collaborative approach.
      The study team partnered with residents to reduce unnecessary laboratory tests
      and associated costs through multilevel interventions across the academic medical
      center. The study team selected laboratory tests for intervention based on cost,
      volume, and ordering frequency (complete blood count [CBC] and CBC with
      differential, common electrolytes, blood enzymes, and liver function tests).
      Interventions were designed collaboratively with residents and targeted
      components of ordering behavior, including system changes, teaching, social
      marketing, academic detailing, financial incentives, and audit/feedback.
      Laboratory ordering was reduced by 8% cumulatively over 3 years, saving $2 019
      000. By involving residents at every stage of the intervention and targeting
      multiple levels simultaneously, laboratory utilization was reduced and cost
      savings were sustained over 3 years. 

PMID- 24443315
TI  - CTF meeting 2012: Translation of the basic understanding of the biology and
      genetics of NF1, NF2, and schwannomatosis toward the development of effective
      therapies.
AB  - The neurofibromatoses (NF) are autosomal dominant genetic disorders that
      encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more
      people worldwide than Duchenne muscular dystrophy and Huntington's disease
      combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes
      (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1
      were identified in a subpopulation of schwannomatosis patients, additional
      causative gene mutations are still to be discovered. Individuals with NF1 may
      demonstrate manifestations in multiple organ systems, including tumors of the
      nervous system, learning disabilities, and physical disfigurement. NF2 ultimately
      can cause deafness, cranial nerve deficits, and additional severe morbidities
      caused by tumors of the nervous system. Unmanageable pain is a key finding in
      patients with schwannomatosis. Although today there is no marketed treatment for
      NF-related tumors, a significant number of clinical trials have become available.
      In addition, significant preclinical efforts have led to a more rational
      selection of potential drug candidates for NF trials. An important element in
      fueling this progress is the sharing of knowledge. For over 20 years the
      Children's Tumor Foundation has convened an annual NF Conference, bringing
      together NF professionals to share novel findings, ideas, and build
      collaborations. The 2012 NF Conference held in New Orleans hosted over 350 NF
      researchers and clinicians. This article provides a synthesis of the highlights
      presented at the conference and as such, is a "state-of-the-field" for NF
      research in 2012.

PMID- 24443318
TI  - Face-to-face handoff: improving transfer to the pediatric intensive care unit
      after cardiac surgery.
AB  - The goal was to develop and implement a comprehensive, primarily face-to-face
      handoff process that begins in the operating room and concludes at the bedside in
      the intensive care unit (ICU) for pediatric patients undergoing congenital heart
      surgery. Involving all stakeholders in the planning phase, the framework of the
      handoff system encompassed a combination of a formalized handoff tool, focused
      process steps that occurred prior to patient arrival in the ICU, and an emphasis
      on face-to-face communication at the conclusion of the handoff. The final process
      was evaluated by the use of observer checklists to examine quality metrics and
      timing for all patients admitted to the ICU following cardiac surgery. The
      process was found to improve how various providers view the efficiency of
      handoff, the ease of asking questions at each step, and the overall capability to
      improve patient care regardless of overall surgical complexity. 

PMID- 24443319
TI  - Barriers to and facilitators of interprofessional-interdepartmental
      interventions: unearthing departmental culture.
AB  - This study evaluates how emergency department (ED) and medical intensive care
      unit (MICU) providers interact in the setting of a quality improvement project
      designed to enhance transport/care for patients from the ED to the MICU. Focus
      groups were conducted with nurses, residents, physician assistants, and
      physicians from the ED and MICU at baseline and 6 months regarding their thoughts
      on and perspectives of the intervention and working with colleagues from another
      department. Data were then analyzed utilizing a multistep coding scheme that
      identified key barriers to and facilitators of the interprofessional
      interdepartmental intervention. Analysis also showed, however, that variances in
      departmental culture play a significant role in the willingness and ability of
      providers to practice interdepartmental team-based care. It is argued that
      anticipating and acknowledging these differences and designing systems to address
      them prior to launch will be essential to the development and implementation of
      effective interdepartmental quality improvement interventions. 

PMID- 24443320
TI  - A rapid DNA extraction method suitable for human papillomavirus detection.
AB  - Infection with oncogenic human papillomavirus (HPV) genotypes is necessary for
      the development of cervical cancer. Testing for HPV DNA from liquid based
      cervical samples can be used as an adjunct to traditional cytological screening.
      In addition there are ongoing viral load, genotyping, and prevalence studies.
      Therefore, a sensitive DNA extraction method is needed to maximize the efficiency
      of HPV DNA detection. The XytXtract Tissue kit is a DNA extraction kit that is
      rapid and so could be useful for HPV testing, particularly in screening
      protocols. This study was undertaken to determine the suitability of this method
      for HPV detection. DNA extraction from HeLa and Caski cell lines containing HPV
      18 and 16 respectively together with DNA from five liquid based cervical samples
      were used in a HPV PCR assay. DNA was also extracted using the QIAamp DNA mini
      kit (Qiagen, Hilden, Germany) as a comparison. DNA extracts were serially diluted
      and assayed. HPV DNA was successfully detected in cell lines and cervical samples
      using the XytXtract Tissue kit. In addition, the XytXtract method was found to be
      more sensitive than the QIAmp method as determined by a dilution series of the
      extracted DNA. While the XytXtract method is a closed, the QIAamp method uses a
      spin column with possible loss of DNA through DNA binding competition of the
      matrix, which could impact on the final extraction efficiency. The XytXtract is a
      cheap, rapid and efficient method for extracting HPV DNA from both cell lines and
      liquid based cervical samples.

PMID- 24443322
TI  - Nutritional intake, body mass index, and activity in postacute traumatic brain
      injury: a preliminary study.
AB  - PURPOSE: In the United States, traumatic brain injury (TBI) remains a serious
      health problem contributing to lifelong disability. Little has been written about
      nutrition problems experienced postrehabilitation discharge. Our objective was to
      describe the nutrition and weight management characteristics of TBI survivors
      after discharge from rehabilitation and to identify characteristics of
      individuals at risk for weight control issues. METHOD/DESIGN: Twenty-six TBI
      survivors admitted to a freestanding rehabilitation hospital were followed for 1
      year postdischarge. Data on height, weight, disability rating, diet and activity
      were collected at admission, 3, 6, 9 and 12 months after discharge. FINDINGS:
      Approximately 30% of the participants showed an increasing body mass index from
      discharge to 1-year follow up. Two patients had more complete long-term data and
      are highlighted. CONCLUSION/CLINICAL RELEVANCE: The case studies provide insight
      into the need for rehabilitation nurses to provide nutrition education to TBI
      survivors that will accommodate changes in lifestyle and activity after
      discharge.

PMID- 24443321
TI  - Origin and pharmacological modulation of tumor-associated regulatory dendritic
      cells.
AB  - Protumorigenic activity of immune regulatory cells has been proven to play a
      major role in precluding immunosurveillance and limiting the efficacy of
      anticancer therapies. Although several approaches have been offered to deplete
      myeloid-derived suppressor cells (MDSC) and regulatory T cells, there are no data
      on how to control suppressive dendritic cell (DC) accumulation or function in the
      tumor environment. Although immunosuppressive function of DC in cancer was
      implicated to immature and plasmacytoid DC, details of how conventional DC (cDC)
      develop immunosuppressive properties remain less understood. Here, we show that
      the development of lung cancer in mice was associated with fast accumulation of
      regulatory DC (regDC) prior to the appearance of MDSC. Using the in vitro and in
      vivo approaches, we demonstrated that (i)both cDC and MDSC could be polarized
      into protumor regDC in the lung cancer environment; (ii) cDC -> regDC
      polarization was mediated by the small Rho GTPase signaling, which could be
      controlled by noncytotoxic doses of paclitaxel; and (iii) prevention of regDC
      appearance increased the antitumor potential of DC vaccine in lung cancer. These
      findings not only bring new players to the family of myeloid regulatory cells and
      provide new targets for cancer therapy, but offer novel insights into the
      immunomodulatory capacity of chemotherapeutic agents used in low, noncytotoxic
      doses.

PMID- 24443324
TI  - Trabecular bone score: a noninvasive analytical method based upon the DXA image.
AB  - The trabecular bone score (TBS) is a gray-level textural metric that can be
      extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry
      (DXA) image. TBS is related to bone microarchitecture and provides skeletal
      information that is not captured from the standard bone mineral density (BMD)
      measurement. Based on experimental variograms of the projected DXA image, TBS has
      the potential to discern differences between DXA scans that show similar BMD
      measurements. An elevated TBS value correlates with better skeletal
      microstructure; a low TBS value correlates with weaker skeletal microstructure.
      Lumbar spine TBS has been evaluated in cross-sectional and longitudinal studies.
      The following conclusions are based upon publications reviewed in this article:
      1) TBS gives lower values in postmenopausal women and in men with previous
      fragility fractures than their nonfractured counterparts; 2) TBS is complementary
      to data available by lumbar spine DXA measurements; 3) TBS results are lower in
      women who have sustained a fragility fracture but in whom DXA does not indicate
      osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar
      spine BMD measurements in postmenopausal women; 5) efficacious therapies for
      osteoporosis differ in the extent to which they influence the TBS; 6) TBS is
      associated with fracture risk in individuals with conditions related to reduced
      bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as
      an emerging technology that could well become a valuable clinical tool in the
      diagnosis of osteoporosis and in fracture risk assessment.

PMID- 24443325
TI  - Dietary fat and protein intake are not associated with incident biliary sludge
      and stones during pregnancy.
AB  - BACKGROUND: Dietary composition can cause insulin resistance, elevated serum
      lipid levels, and obesity, all of which predispose to gallstone formation. The
      effects of dietary fat (including individual fatty acids) and protein on
      gallstone formation are controversial. The aim of this study was to examine the
      effects of dietary fat and protein intake on incident gallstone disease during
      pregnancy, a high-risk time for stone formation. METHODS: We prospectively
      studied 3070 pregnant women who underwent serial gallbladder ultrasound
      examinations during pregnancy and at 4-6 weeks postpartum. All women had at least
      2 study ultrasounds for comparison. A semi-quantitative food frequency
      questionnaire was completed by subjects in the early third trimester.
      Multivariate logistic regression was performed to assess the risk of incident
      gallbladder disease across quartiles of intake of total fat, individual fatty
      acids (polyunsaturated, monounsaturated, saturated, and total trans-fatty acids,
      as well as cholesterol), protein, and protein subtype (animal or vegetable
      based). RESULTS: The cumulative incidence of new biliary sludge/stones or
      progression of baseline sludge to stones was 10.2% by 4-6 weeks postpartum. There
      was no association between total dietary fat (odds ratio [OR], 1.18; 95%
      confidence interval [CI], 0.64-2.18 comparing lowest and highest quartiles) or
      protein intake (OR, 0.83; 95% CI, 0.44-1.22 comparing lowest and highest
      quartiles) and incident gallbladder disease. There was also no association
      between individual fatty acids or protein subtype and gallbladder disease.
      CONCLUSIONS: Neither total nor subtype of dietary fat or protein was associated
      with incident biliary stone or sludge formation in this cohort of pregnant women.

PMID- 24443326
TI  - Physiology and growth of advance Picea rubens and Abies balsamea regeneration
      following different canopy openings.
AB  - We examined the ecophysiology and growth of 0.3-1.3 m tall advance red spruce
      (Picea rubens Sarg.) and balsam fir (Abies balsamea [L.] Mill.) regeneration
      during a 5-year period following the application of different harvest types
      producing three sizes of canopy openings: (i) small gaps (<100 m(2) in area; SMA)
      created by partial uniform single-tree harvest; (ii) irregular gaps of
      intermediate size (100-300 m(2); INT) created by group-selection harvest (removal
      of groups of trees, mainly balsam fir, with uniform partial removal between
      groups); and (iii) large circular gaps (700 m(2); LAR) created by patch-selection
      harvest (removal of trees in 30-m diameter circular areas with uniform partial
      removal between gaps). An unharvested control (CON) was monitored for comparison.
      At the ecophysiological level, we mainly found differences in light-saturated
      photosynthesis of red spruce and specific leaf area of balsam fir among
      treatments. Consequently, we observed good height growth of both species in CON
      and INT, but fir surpassed spruce in SMA and LAR. Results suggest that
      intermediate 100-300 m(2) irregular openings create microenvironmental conditions
      that may promote short-term ecophysiology and growth of red spruce, allowing the
      species to compete with balsam fir advance regeneration. Finally, results
      observed for spruce in large 700-m(2) openings confirm its inability to grow as
      rapidly as fir in comparable open conditions.

PMID- 24443323
TI  - Subdiffractive microscopy: techniques, applications, and challenges.
AB  - Cellular processes rely on the precise orchestration of signaling and effector
      molecules in space and time, yet it remains challenging to gain a comprehensive
      picture of the molecular organization underlying most basic biological functions.
      This organization often takes place at length scales below the resolving power of
      conventional microscopy. In recent years, several 'superresolution' fluorescence
      microscopic techniques have emerged that can surpass the diffraction limit of
      conventional microscopy by a factor of 2-20. These methods have been used to
      reveal previously unknown organization of macromolecular complexes and
      cytoskeletal structures. The resulting high-resolution view of molecular
      organization and dynamics is already changing our understanding of cellular
      processes at the systems level. However, current subdiffractive microscopic
      techniques are not without limitations; challenges remain to be overcome before
      these techniques achieve their full potential. Here, we introduce three primary
      types of subdiffractive microscopic techniques, consider their current
      limitations and challenges, and discuss recent biological applications.

PMID- 24443327
TI  - Predictability, efficacy and safety of radiosensitization of glioblastoma
      initiating cells by the ATM inhibitor KU-60019.
AB  - We have previously shown that pharmacological inhibition of ataxia telangiectasia
      mutated (ATM) protein sensitizes glioblastoma-initiating cells (GICs) to ionizing
      radiation (IR). Herein, we report the experimental conditions to overcome GIC
      radioresistance in vitro using the specific ATM inhibitor KU-60019, two major
      determinants of the tumor response to this drug and the absence of toxicity of
      this treatment in vitro and in vivo. Repeated treatments with KU-60019 followed
      by IR substantially delayed GIC proliferation in vitro and even eradicated
      radioresistant cells, whereas GIC treated with vehicle plus radiation recovered
      early and expanded. The tumor response to the drug occurred under a cutoff level
      of expression of TP53 and over a cutoff level of expression of
      phosphatidylinositol 3-kinase (PI3K). No increased clastogenicity or point
      mutagenicity was induced by KU-60019 plus radiation when compared to vehicle plus
      radiation. No significant histological changes to the brain or other organs were
      observed after prolonged infusion into the brain of KU-60019 at millimolar
      concentrations. Taken together, these findings suggest that GIC-driven tumors
      with low expression of TP53 and high expression of PI3K might be effectively and
      safely radiosensitized by KU-60019. 

PMID- 24443328
TI  - Fyn kinase-regulated NMDA receptor- and AMPA receptor-dependent pain
      sensitization in spinal dorsal horn of mice.
AB  - BACKGROUND: Inhibition of Src-family protein tyrosine kinases (SFKs) in spinal
      dorsal horn has been established as an effective strategy for the alleviation of
      chronic pathological pain. As one of the important SFKs members, Fyn kinase is
      critical for synaptic plasticity and many pathophysiological processes. However,
      whether Fyn is involved in spinal sensitization is far from being elucidated.
      METHOD: We manipulated Fyn activity by expressing a constitutively active Fyn
      mutant [Fyn(Y528F) ] or a catalytically null mutant [Fyn(K296M) ] in the spinal
      dorsal horn of mice, and performed behavioural and biochemical experiments to
      investigate the role of Fyn in regulating the nociceptive responses and the
      synaptic expression of ionotropic glutamate receptors. RESULTS: Spinal expression
      of Fyn(Y528F) alone in intact mice was sufficient to elicit persistent mechanical
      allodynia and thermal hyperalgesia, which lasted for at least 12 days. Fyn(Y528F)
      simultaneously enhanced the concentrations of N-methyl-D-aspartic acid (NMDA)
      subtype and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      subtype glutamate receptors at synaptosomal membrane fraction. Pharmacological
      inhibition of NMDA receptors or AMPA receptors greatly alleviated Fyn(Y528F)
      induced pain hypersensitivity. To evaluate the contribution of Fyn to
      inflammatory pain, we expressed Fyn(K296M) before intradermal injection of
      complete Freund's adjuvant (CFA), finding that Fyn(K296M) had no effect on the
      induction of inflammatory pain within 3 h post-CFA injection, which, however,
      repressed the synaptic accumulation of NMDA receptors and AMPA receptors to
      attenuate the maintenance of chronic pain states. CONCLUSION: Fyn played a key
      role in the sustained sensitization of nociceptive behaviours by up-regulating
      the functions of ionotropic glutamate receptors in spinal dorsal horn.

PMID- 24443329
TI  - Palladium-catalyzed aza-Wittig-type condensation of isoxazol-5(4H)-ones with
      aldehydes.
AB  - This paper describes the development of a palladium-catalyzed decarboxylative
      inter- and intramolecular condensation reaction of isoxazol-5(4 H)-ones with
      carbonyl compounds in the presence of PPh3 , giving various 2-azabuta-1,3-dienes
      or pyrroles in moderate to high yields. 

PMID- 24443330
TI  - SNAI2 mutation causes human piebaldism.

PMID- 24443331
TI  - Quality of life in autism across the lifespan: a meta-analysis.
AB  - Autism is a lifelong neurodevelopmental disorder, with a known impact on quality
      of life. Yet the developmental trajectory of quality of life is not well
      understood. First, the effect of age on quality of life was studied with a meta
      analysis. Our meta-analysis included 10 studies (published between 2004 and 2012)
      with a combined sample size of 486 people with autism and 17,776 controls.
      Second, as there were no studies on quality of life of the elderly with autism,
      we conducted an empirical study on quality of life of the elderly (age range 53
      83) with autism (N = 24) and without autism (N = 24). The meta-analysis showed
      that quality of life is lower for people with autism compared to people without
      autism, and that the mean effect is large (Cohen's d = -0.96). Age did not have
      an effect on quality of life. The study concerning the elderly with autism showed
      that the difference in quality of life is similar in the elderly. Age, IQ and
      symptom severity did not predict quality of life in this sample. Across the
      lifespan, people with autism experience a much lower quality of life compared to
      people without autism. Hence, the quality of life seemed to be independent of
      someone's age. 

PMID- 24443332
TI  - Massive consolidation: a rare manifestation of paediatric Scrub typhus.
AB  - Despite resurgence in the number of Scrub typhus cases, it still poses a
      diagnostic challenge as there is no prototype presentation. We report a case of a
      child with Scrub typhus who developed a massive consolidation. Despite such an
      extensive consolidation, respiratory symptoms such as cough and breathlessness
      were inconspicuous thereby posing a diagnostic dilemma. Upon serological
      confirmation, doxycycline therapy was initiated with a rapid and complete
      resolution of the pneumonia, both clinically and radiologically. The case is
      being reported to highlight this unusual presentation of Scrub typhus in
      children. 

PMID- 24443333
TI  - Acute gross painless transudative ascites in a patient with lupus.
AB  - Gross ascites is a rare presentation of lupus. Ascites in lupus may be due to
      lupus peritonitis or secondary to one of the complications including nephrotic
      syndrome. The ascites due to lupus peritonitis has been described as exudative
      with a serum-ascites albumin gradient (SAAG) below 11 g/L, unless associated with
      nephrotic syndrome. We report an unusual case of lupus ascites in a 23-year-old
      woman who presented with acute painless gross ascites with no constitutional,
      skin or musculoskeletal symptoms of a lupus flare. The ascites was a transudate
      with SAAG above 11 g/L with no associated nephrotic syndrome. She was treated
      with corticosteroids, mycophenolate mofetil and diuretics with a good response
      and no recurrence of her ascites. 

PMID- 24443334
TI  - Non-traumatic compartment syndrome secondary to deep vein thrombosis and
      anticoagulation.
AB  - We describe an unusual case of non-traumatic compartment syndrome in three
      compartments of the left lower limb in a 57-year-old male inpatient. He had
      recently been started on anticoagulation therapy for multiple pulmonary emboli
      and deep vein thrombosis of the left posterior tibial and peroneal veins. Three
      of the four osteofascial compartments had pressures above 70 mm Hg, hence four
      compartment fasciotomies were performed. Postoperatively, intravenous heparin
      therapy was started resulting in a significant blood loss, but he had no
      neurovascular deficit. At reoperation, for primary wound closure, his tissues
      looked healthy. Non-traumatic causes of acute compartment syndrome, including
      deep venous thrombosis and anticoagulation, are considered. 

PMID- 24443335
TI  - Polycystic liver disease.
AB  - A widespread use of ultrasound (US) examination is contributing to an increase in
      the diagnosis of renal and hepatic cysts. However, the vast majority of these
      lesions are benign with an indolent course during the patient's lifespan. Adult
      polycystic kidney disease (APKD) is one of the most common diagnosed entities.
      APKD is a genetic disease defined by the presence of multiple kidney cysts,
      occasionally accompanied by hepatic cysts. The presence of hepatic cysts sparing
      kidneys is very rare and thereby must be assumed as a different clinical entity.
      This article describes a case of an exuberant hepatomegaly due to the presence of
      isolated multiple hepatic cysts without renal involvement. 

PMID- 24443336
TI  - Haemorrhagic cholecystitis: an unusual cause of upper gastrointestinal bleeding.
AB  - Haemorrhagic cholecystitis is a rare cause of upper gastrointestinal bleeding and
      is a difficult diagnosis to make. This case report describes an orthopaedic
      patient, who developed deranged liver function tests and anaemia after a
      hemiarthroplasty of the hip. The patient had upper abdominal pain and black
      stools which clinically appeared to be melaena. An ultrasound scan of the abdomen
      was inconclusive, and therefore a CT was performed and the potential diagnosis of
      haemorrhagic cholecystitis was raised. An endoscopic evaluation of the upper
      gastrointestinal tract showed no evidence of other causes of upper
      gastrointestinal bleeding. Following an emergency laparotomy and cholecystectomy,
      she recovered well. This report aims to increase awareness about the uncommon
      condition of haemorrhagic cholecystitis, and to educate regarding clinical and
      radiological signs which lead to this diagnosis. 

PMID- 24443337
TI  - Focal eventration of diaphragm with fat content.

PMID- 24443339
TI  - Spontaneous cerebrospinal fluid rhinorrhoea: a rare clinical entity.

PMID- 24443338
TI  - A mycotic abdominal aortic aneurysm caused by Listeria monocytogenes in a patient
      with HIV infection.
AB  - A 65-year-old man with HIV infection presented with acute severe abdominal pain
      radiating to the back. A CT scan revealed an infrarenal abdominal aortic
      aneurysm, and an aortobifemoral bypass was undertaken. Subsequently, tissue
      specimens from the aortic wall grew Listeria monocytogenes. The patient received
      8 weeks of intravenous antibiotic treatment followed by oral sulfotrim as
      secondary prophylaxis and made an uneventful recovery. 

PMID- 24443340
TI  - Atypical presentation of typical carcinoid.
AB  - Bronchial carcinoid tumours can present with symptoms of distal airway
      obstruction, local airway irritation or bleeding due to hypervascularity.
      Presentation with a spontaneous pneumothorax (SP) is rare. We present a case of
      typical endobronchial carcinoid tumour that presented with a SP. We explored the
      possible mechanisms of this rare presentation, especially the check-valve
      mechanism of airway obstruction, which was evident during the fiberoptic
      bronchoscopic examination. 

PMID- 24443341
TI  - Retinal tissue in mature cystic teratoma of ovary presenting with full-term
      pregnancy.
AB  - Mature cystic teratomas are benign ovarian neoplasms which account for around 95%
      of all ovarian germ cell tumours and contain tissues derived from two or three
      embryonic germ layers. These tumours are frequently diagnosed in women of
      reproductive age group and can result in fetomaternal distress if concurrent
      pregnancy occurs. The authors describe a case of successful natural pregnancy in
      a 30-year-old woman with coexisting mature cystic teratoma of ovary that
      culminated in viable childbirth at term. Subsequent histopathological examination
      of the tumour revealed a mature teratoma composed predominantly of ectodermal
      elements along with retinal tissues--a rare finding that prompted this case
      report.

PMID- 24443342
TI  - Rare anatomical variation in transverse sinuses (duplication on right, hypoplasia
      of left) falsely mimicking transverse sinus thrombosis probably due to resultant
      slow flow.

PMID- 24443343
TI  - Rupture of the infrarenal abdominal aortic aneurysm (AAA) following an
      endovascular aneurysm repair (EVAR) due to an isolated type II endoleak.
AB  - We present a case of an elderly man with the persisting type II endoleak
      following endovascular aneurysm repair. In a view of the multiple comorbidities,
      the patient was denied an open elective repair. However, when presented with a
      ruptured aneurismal sac, he underwent an emergency open abdominal aortic aneurysm
      repair. Overall, the patient has made a good postoperative recovery. 

PMID- 24443344
TI  - First mouse model for combined osteogenesis imperfecta and Ehlers-Danlos
      syndrome.
AB  - By using a genome-wide N-ethyl-N-nitrosourea (ENU)-induced dominant mutagenesis
      screen in mice, a founder with low bone mineral density (BMD) was identified.
      Mapping and sequencing revealed a T to C transition in a splice donor of the
      collagen alpha1 type I (Col1a1) gene, resulting in the skipping of exon 9 and a
      predicted 18-amino acid deletion within the N-terminal region of the triple
      helical domain of Col1a1. Col1a1(Jrt) /+ mice were smaller in size, had lower BMD
      associated with decreased bone volume/tissue volume (BV/TV) and reduced
      trabecular number, and furthermore exhibited mechanically weak, brittle, fracture
      prone bones, a hallmark of osteogenesis imperfecta (OI). Several markers of
      osteoblast differentiation were upregulated in mutant bone, and histomorphometry
      showed that the proportion of trabecular bone surfaces covered by activated
      osteoblasts (Ob.S/BS and N.Ob/BS) was elevated, but bone surfaces undergoing
      resorption (Oc.S/BS and N.Oc/BS) were not. The number of bone marrow stromal
      osteoprogenitors (CFU-ALP) was unaffected, but mineralization was decreased in
      cultures from young Col1a1(Jrt) /+ versus +/+ mice. Total collagen and type I
      collagen content of matrices deposited by Col1a1(Jrt) /+ dermal fibroblasts in
      culture was ~40% and 30%, respectively, that of +/+ cells, suggesting that mutant
      collagen chains exerted a dominant negative effect on type I collagen
      biosynthesis. Mutant collagen fibrils were also markedly smaller in diameter than
      +/+ fibrils in bone, tendon, and extracellular matrices deposited by dermal
      fibroblasts in vitro. Col1a1(Jrt) /+ mice also exhibited traits associated with
      Ehlers-Danlos syndrome (EDS): Their skin had reduced tensile properties, tail
      tendon appeared more frayed, and a third of the young adult mice had noticeable
      curvature of the spine. Col1a1(Jrt) /+ is the first reported model of combined
      OI/EDS and will be useful for exploring aspects of OI and EDS pathophysiology and
      treatment.

PMID- 24443345
TI  - Transitioning adolescents and young adults with spina bifida to adult healthcare:
      initial findings from a model program.
AB  - PURPOSE: The Spina Bifida Transition Project (SBTP) was developed by partners
      from pediatric and adult health care settings using existing best practice
      information in an effort to transition adolescents to adult health care
      providers. The purpose of this manuscript is to present the results of an initial
      evaluation of the SBTP from the adolescent/young adult (AYA) and family
      perspective. DESIGN AND METHODS: Qualitative evaluation data were obtained from
      telephone interviews with 40 individuals (24 AYA and 16 parents representing 28
      families) two-three weeks after initial adult clinic visits using a semi
      structured interview guide. FINDINGS: Interview analysis yielded six overall
      themes: Positive experience, Developing Trust, Unexpected Benefits,
      Communication, Potential Worries, and Suggestions for Improvement. The study
      supported both the effectiveness of the SBTP as well as patient desire for
      earlier initiation of transition activities CONCLUSION AND CLINICAL RELEVANCE:
      SBTP is well-received by participants and their parents and may be useful model
      for other chronic health conditions.

PMID- 24443347
TI  - Mechanism of inhibition on L929 rat fibroblasts proliferation induced by
      potential adhesion barrier material poly(p-dioxanone-co-L-phenylalanine)
      electrospun membranes.
AB  - Fibroblast plays an important role in the occurrence of postoperative tissue
      adhesion; materials that have particular "cell-material" interactions to inhibit
      proliferation of fibroblast will be excellent potential adhesion barriers. In the
      current study, we synthesized copolymers of p-dioxanone and L-phenylalanine
      (PDPA) and evaluated the mechanism of its particular inhibition effect on L929
      fibroblast proliferation when used as a culture surface. PDPA electrospun
      membranes could induce apoptosis of L929 fibroblasts. We hypothesized there were
      two reasons for the apoptosis induction: one was the ability to facilitate cell
      adhesion of materials, and the other was production of the degradation product, L
      phenylalanine. Ninhydrin colorimetric results revealed that L-phenylalanine was
      continuously released during the culture process and could induce apoptosis in
      L929 cells. Relatively poor cell adhesion and constant release of L-phenylalanine
      made PDPA-1 to be the most efficient polymer for the induction of apoptosis.
      Analysis of apoptosis-related genes revealed that PDPA-induced apoptosis might be
      performed in a mitochondrial-dependent pathway. But poly(p-dioxanone)-induced
      apoptosis might occur in a c-Myc independent pathway that was different from
      PDPA.

PMID- 24443348
TI  - Maintaining skeletal muscle mass: lessons learned from hibernation.
AB  - Muscle disuse and starvation are often associated with a catabolic response
      leading to a dramatic loss of skeletal muscle mass. Hibernating animals represent
      a unique situation where muscle mass is maintained despite prolonged periods of
      immobilization and lack of nutrition. We analysed the molecular pathways
      upregulated during hibernation in an obligate hibernator, the 13-lined ground
      squirrel (Ictidomys tridecemlineatus). Although Akt has an established role in
      skeletal muscle maintenance, we found that activated Akt was decreased in
      skeletal muscle of hibernating squirrels. Another serine-threonine kinase, serum-
      and glucocorticoid-regulated kinase 1 (SGK1), was upregulated during hibernation
      and contributed to protection from loss of muscle mass via downregulation of
      proteolysis and autophagy and via an increase in protein synthesis. We extended
      our observations to non-hibernating animals and demonstrated that SGK1-null mice
      developed muscle atrophy. These mice displayed an exaggerated response to
      immobilization and starvation. Furthermore, SGK1 overexpression prevented
      immobilization-induced muscle atrophy. Taken together, our results identify SGK1
      as a novel therapeutic target to combat skeletal muscle loss in acquired and
      inherited forms of muscle atrophy. 

PMID- 24443349
TI  - Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic
      intermittent hypoxia.
AB  - Respiratory muscle dysfunction documented in sleep apnoea patients is perhaps due
      to oxidative stress secondary to chronic intermittent hypoxia (CIH). We sought to
      explore the effects of different CIH protocols on respiratory muscle form and
      function in a rodent model. Adult male Wistar rats were exposed to CIH (n = 32)
      consisting of 90 s normoxia-90 s hypoxia (either 10 or 5% oxygen at the nadir;
      arterial O2 saturation ~ 90 or 80%, respectively] for 8 h per day or to sham
      treatment (air-air, n = 32) for 1 or 2 weeks. Three additional groups of CIH
      treated rats (5% O2 for 2 weeks) had free access to water containing N-acetyl
      cysteine (1% NAC, n = 8), tempol (1 mM, n = 8) or apocynin (2 mM, n = 8).
      Functional properties of the diaphragm muscle were examined ex vivo at 35 
      degrees C. The myosin heavy chain and sarco(endo)plasmic reticulum Ca(2+)-ATPase
      isoform distribution, succinate dehydrogenase and glyercol phosphate
      dehydrogenase enzyme activities, Na(+)-K(+)-ATPase pump content, concentration of
      thiobarbituric acid reactive substances, DNA oxidation and antioxidant capacity
      were determined. Chronic intermittent hypoxia (5% oxygen at the nadir; 2 weeks)
      decreased diaphragm muscle force and endurance. All three drugs reversed the
      deleterious effects of CIH on diaphragm endurance, but only NAC prevented CIH
      induced diaphragm weakness. Chronic intermittent hypoxia increased diaphragm
      muscle myosin heavy chain 2B areal density and oxidized glutathione/reduced
      glutathione (GSSG/GSH) ratio. We conclude that CIH-induced diaphragm dysfunction
      is reactive oxygen species dependent. N-Acetyl cysteine was most effective in
      reversing CIH-induced effects on diaphragm. Our results suggest that respiratory
      muscle dysfunction in sleep apnoea may be the result of oxidative stress and, as
      such, antioxidant treatment could prove a useful adjunctive therapy for the
      disorder.

PMID- 24443350
TI  - Age and sex differences in muscle sympathetic nerve activity in relation to
      haemodynamics, blood volume and left ventricular size.
AB  - We compared the effect of age- and sex-related differences in haemodynamics,
      blood volume (BV) and left ventricular (LV) size and mass on resting muscle
      sympathetic nerve activity (MSNA) in healthy, normotensive adults. Twenty young
      men (19-47 years old) and 20 young women (21-46 years old) as well as 15 older
      men (62-80 years old) and 15 older women (60-82 years old) were studied. Cardiac
      output (acetylene rebreathing), total peripheral resistance, forearm vascular
      resistance (FVR; venous occlusion plethysmography) and MSNA were measured during
      supine rest. Blood volume was calculated (CO rebreathing), and LV mass, end
      diastolic (LVEDV) and end-systolic volumes (LVESV) were measured using magnetic
      resonance imaging. Cardiac index (P < 0.001 and P = 0.016), BV (both P < 0.001),
      LV mass (P < 0.001 and P = 0.002), LVEDV (P < 0.001 and P = 0.002) and LVESV
      (both P < 0.001) were lower in the older and female groups, respectively. Total
      peripheral resistance was significantly higher in the older (P < 0.001) and
      female groups (P = 0.014), but FVR was increased in the female groups (P = 0.048)
      only (age, P = 0.089). The MSNA was greater in the older groups (P < 0.001) only
      (sex, P = 0.228). Increased MSNA was shown to correlate with a decrease in BV (P
      = 0.004) in men only when adjusted for age (women, P = 0.133). There was a
      positive relation between MSNA and FVR (P = 0.020) in men but not women (P =
      0.422). There were no significant relations between MSNA and LV mass, LVEDV or
      LVESV. The findings suggest that the increase in resting MSNA with age may be
      related to the decline in BV in men only, but it is unknown whether sex
      differences in sympathetic adrenergic vasoconstriction occur independently of
      these changes.

PMID- 24443351
TI  - Alterations in Notch signalling in skeletal muscles from mdx and dko dystrophic
      mice and patients with Duchenne muscular dystrophy.
AB  - New Findings What is the central question of this study? The Notch signalling
      pathway plays an important role in muscle regeneration, and activation of the
      pathway has been shown to enhance muscle regeneration in aged mice. It is unknown
      whether Notch activation will have a similarly beneficial effect on muscle
      regeneration in the context of Duchenne muscular dystrophy (DMD). What is the
      main finding and its importance? Although expression of Notch signalling
      components is altered in both mouse models of DMD and in human DMD patients,
      activation of the Notch signalling pathway does not confer any functional benefit
      on muscles from dystrophic mice, suggesting that other signalling pathways may be
      more fruitful targets for manipulation in treating DMD. Abstract In Duchenne
      muscular dystrophy (DMD), muscle damage and impaired regeneration lead to
      progressive muscle wasting, weakness and premature death. The Notch signalling
      pathway represents a central regulator of gene expression and is critical for
      cellular proliferation, differentiation and apoptotic signalling during all
      stages of embryonic muscle development. Notch activation improves muscle
      regeneration in aged mice, but its potential to restore regeneration and function
      in muscular dystrophy is unknown. We performed a comprehensive examination of
      several genes involved in Notch signalling in muscles from dystrophin-deficient
      mdx and dko (utrophin- and dystrophin-null) mice and DMD patients. A reduction of
      Notch1 and Hes1 mRNA in tibialis anterior muscles of dko mice and quadriceps
      muscles of DMD patients and a reduction of Hes1 mRNA in the diaphragm of the mdx
      mice were observed, with other targets being inconsistent across species.
      Activation and inhibition of Notch signalling, followed by measures of muscle
      regeneration and function, were performed in the mouse models of DMD. Notch
      activation had no effect on functional regeneration in C57BL/10, mdx or dko mice.
      Notch inhibition significantly depressed the frequency-force relationship in
      regenerating muscles of C57BL/10 and mdx mice after injury, indicating reduced
      force at each stimulation frequency, but enhanced the frequency-force
      relationship in muscles from dko mice. We conclude that while Notch inhibition
      produces slight functional defects in dystrophic muscle, Notch activation does
      not significantly improve muscle regeneration in murine models of muscular
      dystrophy. Furthermore, the inconsistent expression of Notch targets between
      murine models and DMD patients suggests caution when making interspecies
      comparisons. 

PMID- 24443352
TI  - The role of brain natriuretic peptide in maintaining myometrial quiescence during
      pregnancy.
AB  - Myometrial quiescence is a physiological stage of the myometrium during
      pregnancy. It is a period of active relaxation of the myometrial smooth muscle
      cells; myometrial quiescence is responsible for maintaining pregnancy. The
      precise mechanisms underlying myometrial quiescence have not been completely
      elucidated, although many mediators and cellular pathways have been described as
      playing a role. Fetal membranes (chorion and amnion) produce and release one or
      more substances that inhibit myometrial contractions, playing a central role in
      the maintenance of myometrial quiescence. Brain natriuretic peptide (BNP) is more
      potent than any other natriuretic peptide in inhibiting myometrial contractions
      in vitro. Brain natriuretic peptide is produced by the chorion and amnion, mainly
      during myometrial quiescence, and decreasing towards the end of pregnancy.
      Production of BNP is reduced in fetal membranes obtained from women in preterm
      labour. It is postulated that BNP, acting in a paracrine fashion, plays a key
      role in the maintaining myometrial quiescence and, therefore, controlling the
      duration of pregnancy. Furthermore, it is postulated that a premature decrease of
      BNP production by the fetal membranes may cause preterm labour and preterm birth.

PMID- 24443354
TI  - Clinical and radiographic findings in adults with persistent hypophosphatasemia.
AB  - A serum alkaline phosphatase value below the age-adjusted lower limits of normal
      (hypophosphatasemia) is uncommonly encountered in clinical practice. The
      electronic and paper medical records of 885,165 patients treated between 2002 and
      2012 at a large, rural, multispecialty health clinic were interrogated to
      estimate the prevalence and characterize the clinical and radiographic findings
      of adults whose serum alkaline phosphatase was almost always low (persistent
      hypophosphatasemia). We hypothesized that some of these patients might harbor
      previously unrecognized hypophosphatasia, a rare, inherited condition of impaired
      mineralization of bones and teeth. Persistent hypophosphatasemia (serum alkaline
      phosphatase <= 30 IU/L) was found in 1 of 1544 adult patients. These adult
      patients had more crystalline arthritis, orthopedic surgery, chondrocalcinosis,
      calcific periarthritis, enthesopathy, and diffuse idiopathic skeletal
      hyperostosis than a general adult patient population. A gender effect was
      observed. The clinical and radiographic findings of adult patients with
      persistent hypophosphatasemia resemble those of the adult form of
      hypophosphatasia. Clinicians should take notice of persistent hypophosphatasemia,
      consider the diagnosis of hypophosphatasia, and be cautious when considering
      potent anti-remodeling therapy in these adults. This population warrants further
      evaluation.

PMID- 24443353
TI  - A plasminogen activator inhibitor type 1 mutant retards diabetic nephropathy in
      db/db mice by protecting podocytes.
AB  - A mutant non-inhibiting plasminogen activator inhibitor type 1 (PAI-1), termed
      PAI-1R, which reduces endogenous PAI-1 activity, has been shown to inhibit
      albuminuria and reduce glomerulosclerosis in experimental diabetes. The mechanism
      of the reduction of albuminuria is unclear. This study sought to determine
      whether the administration of PAI-1R protected podocytes from injury directly,
      thereby reducing albuminuria in the db/db mouse, a model of type 2 diabetes.
      Untreated uninephrectomized db/db mice developed significant mesangial matrix
      expansion and albuminuria at week 22 of age, associated with segmental podocyte
      foot-process effacement, reduction of renal nephrin, podocin and zonula occludin
      1 production and induction of renal desmin and B7-1 generation. In contrast,
      treatment with PAI-1R at 0.5 mg (kg body weight)(-1) i.p., twice daily from week
      20 to 22, reduced glomerular matrix accumulation, fibronectin and collagen
      production and albuminuria by 36, 62, 65 and 31%, respectively (P < 0.05),
      without affecting blood glucose level or body weight. Podocyte morphology and
      protein markers were also significantly attenuated by PAI-1R administration.
      Importantly, recombinant PAI-1 downregulated nephrin and zonula occludin-1 but
      increased desmin and B7-1 mRNA expression and protein production by podocytes in
      vitro, similar to the effects of transforming growth factor-beta1. These
      observations provide evidence that PAI-1, in a manner similar to transforming
      growth factor-beta1, directly induces podocyte injury, particularly in the
      setting of diabetes, where elevated PAI-1 may contribute to the progression of
      albuminuria. Reducing the increased PAI-1 activity by administration of PAI-1R,
      in fact, reduces podocyte injury, thereby reducing albuminuria. Therefore, PAI-1R
      provides an additional therapeutic effect in slowing the progression of diabetic
      nephropathy via the protection of podocytes. 

PMID- 24443355
TI  - Nonlinear finite element simulations of injuries with free boundaries:
      application to surgical wounds.
AB  - Wound healing is a process driven by biochemical and mechanical variables in
      which a new tissue is synthesised to recover original tissue functionality. Wound
      morphology plays a crucial role in this process, as the skin behaviour is not
      uniform along different directions. In this work, we simulate the contraction of
      surgical wounds, which can be characterised as elongated and deep wounds. Because
      of the regularity of this morphology, we approximate the evolution of the wound
      through its cross section, adopting a plane strain hypothesis. This
      simplification reduces the complexity of the computational problem; while allows
      for a thorough analysis of the role of wound depth in the healing process, an
      aspect of medical and computational relevance that has not yet been addressed. To
      reproduce wound contraction, we consider the role of fibroblasts, myofibroblasts,
      collagen and a generic growth factor. The contraction phenomenon is driven by
      cell-generated forces. We postulate that these forces are adjusted to the
      mechanical environment of the tissue where cells are embedded through a
      mechanosensing and mechanotransduction mechanism. To solve the nonlinear problem,
      we use the finite element method (FEM) and an updated Lagrangian approach to
      represent the change in the geometry. To elucidate the role of wound depth and
      width on the contraction pattern and evolution of the involved species, we
      analyse different wound geometries with the same wound area. We find that deeper
      wounds contract less and reach a maximum contraction rate earlier than
      superficial wounds.

PMID- 24443356
TI  - Conducting scaffolds for liver tissue engineering.
AB  - It is known that there is a correlation between a cell membrane potential and the
      proliferation of the cell. The high proliferation capacity of liver cells can
      also be attributed to its specific cell membrane potential as liver cell is
      recognized as one of the most depolarized of all differentiated cells. We
      hypothesized that this phenomenon can be emphasized by growing liver cells in
      conducting scaffolds that can increase the electrical communication among the
      cells. In this article, using tissue engineering techniques, we grew hepatocyte
      cells in scaffolds with various compositions. It was found that the scaffolds
      containing conducting polymer of poly (3,4-ethylenedioxythiophene) (PEDOT)
      provide the best condition for attachment and proliferation of the cells. More
      specifically, the blend of hyaluronan, PEDOT, and collagen (I) as dopants in
      gelatin-chitosan-based scaffold presented the best cell/scaffold interactions for
      regeneration of liver cells.

PMID- 24443357
TI  - Impact of introduction of 20-week ultrasound scan on prevalence and fetal and
      neonatal outcomes in cases of selected severe congenital heart defects in The
      Netherlands.
AB  - OBJECTIVES: To evaluate in a population-based cohort the effect of the
      introduction of the 20-week ultrasound scan in 2007 on the time of diagnosis,
      pregnancy outcome and total prevalence and liveborn prevalence of cases with
      selected congenital heart defects (CHDs) in The Netherlands. METHODS: We included
      children and fetuses diagnosed with selected severe CHD, born in the 11-year
      period from 2001 to 2011. Two groups of CHD were defined: those associated with
      an abnormal four-chamber view at ultrasound (Group 1), and those associated with
      a normal four-chamber view at ultrasound (Group 2). The time of diagnosis,
      pregnancy outcome and total liveborn prevalence were compared for both groups
      over two 5-year periods, before and after the introduction of the 20-week
      ultrasound scan. Trends in total and liveborn prevalence were examined over 2001
      to 2011. RESULTS: Information was collected on 269 children and fetuses. After
      the introduction of the 20-week ultrasound scan, the prenatal detection rate of
      CHDs increased in both groups (Group 1, 34.6% in 2001-2005 vs 84.8% in 2007-2011
      (P < 0.001); Group 2, 14.3% in 2001-2005 vs 29.6% in 2007-2011 (P = 0.037)). The
      rate of termination of pregnancy (TOP) increased significantly only for Group 1
      (15.4% vs 51.5% (P < 0.001)). The total prevalence of CHD in Group 1 increased
      over time from 2.9 per 10 000 births in 2001 to 6.4 per 10 000 births in 2011 (P
      = 0.016). The liveborn prevalence did not show a trend over time. For Group 2, no
      trends in total or liveborn prevalence could be detected over time. CONCLUSIONS:
      Since the implementation of the routine 20-week ultrasound scan in The
      Netherlands, prenatal detection rate of selected severe CHDs increased
      significantly. Improved prenatal detection was accompanied by a more than three
      fold increase in TOP, although only in those CHDs with an abnormal four-chamber
      view at prenatal ultrasound.

PMID- 24443358
TI  - Disorder of sex development in an infant with molecularly confirmed 46,XY,
      +der(10)t(10;21)(q21.1;q21.3), -21.

PMID- 24443359
TI  - Over one-third of African-American MGUS and multiple myeloma patients are
      carriers of hyperphosphorylated paratarg-7, an autosomal dominantly inherited
      risk factor for MGUS/MM.
AB  - As hyperphosphorylated paratarg-7 (pP-7) carrier state was shown to be the first
      molecularly defined autosomal dominantly inherited risk factor for monoclonal
      gammopathy of unknown significance (MGUS) and multiple myeloma (MM) in a European
      population, the prevalence of pP-7 carrier state among African-Americans who have
      a significantly higher incidence of MGUS/MM is of interest. We therefore
      determined pP-7 carrier state and paraproteins with specificity for P-7 in
      African-American, European and Japanese patients with MGUS/MM and healthy
      controls. By isoelectric focusing and ELISA, a paratarg-7-specific paraprotein
      and the associated pP-7 carrier state was observed in 30/81 (37.0%) African
      American, 42/252 (16.7%) European and 7/176 (4.0%) Japanese MGUS/MM patients (p <
      0.001). A pP-7 carrier state was found in 11/100 (11.0%) African-American, 8/550
      (1.5%) European and 1/278 (0.4%) Japanese healthy controls (p < 0.001), resulting
      in an odds ratio for MGUS/MM of 4.8 (p < 0.001) among African-American, 13.6
      among European (p < 0.001) and 11.5 (p = 0.023) among Japanese carriers of pP-7.
      We conclude that pP-7 carriers are most prevalent among African-Americans, but a
      pP-7 carrier state is the strongest molecularly defined single risk factor for
      MGUS/MM known to date in all three ethnic groups. The high prevalence of pP-7
      carriers among African-American patients emphasizes a predominant role of this
      genetic factor in the pathogenesis of these diseases. The large number of pP7
      African-American patients and controls should facilitate the identification of
      the SNP or mutation underlying the pP-7 carrier state. 

PMID- 24443360
TI  - Sensitive KIT D816V mutation analysis of blood as a diagnostic test in
      mastocytosis.
AB  - The recent progress in sensitive KIT D816V mutation analysis suggests that
      mutation analysis of peripheral blood (PB) represents a promising diagnostic test
      in mastocytosis. However, there is a need for systematic assessment of the
      analytical sensitivity and specificity of the approach in order to establish its
      value in clinical use. We therefore evaluated sensitive KIT D816V mutation
      analysis of PB as a diagnostic test in an entire case-series of adults with
      mastocytosis. We demonstrate for the first time that by using a sufficiently
      sensitive KIT D816V mutation analysis, it is possible to detect the mutation in
      PB in nearly all adult mastocytosis patients. The mutation was detected in PB in
      78 of 83 systemic mastocytosis (94%) and 3 of 4 cutaneous mastocytosis patients
      (75%). The test was 100% specific as determined by analysis of clinically
      relevant control patients who all tested negative. Mutation analysis of PB was
      significantly more sensitive than serum tryptase >20 ng/mL. Of 27 patients with
      low tryptase, 26 tested mutation positive (96%). The test is furthermore readily
      available and we consider the results to serve as a foundation of experimental
      evidence to support the inclusion of the test in diagnostic algorithms and
      clinical practice in mastocytosis.

PMID- 24443361
TI  - Combined climate- and prey-mediated range expansion of Humboldt squid (Dosidicus
      gigas), a large marine predator in the California Current System.
AB  - Climate-driven range shifts are ongoing in pelagic marine environments, and
      ecosystems must respond to combined effects of altered species distributions and
      environmental drivers. Hypoxic oxygen minimum zones (OMZs) in midwater
      environments are shoaling globally; this can affect distributions of species both
      geographically and vertically along with predator-prey dynamics. Humboldt (jumbo)
      squid (Dosidicus gigas) are highly migratory predators adapted to hypoxic
      conditions that may be deleterious to their competitors and predators.
      Consequently, OMZ shoaling may preferentially facilitate foraging opportunities
      for Humboldt squid. With two separate modeling approaches using unique, long-term
      data based on in situ observations of predator, prey, and environmental
      variables, our analyses suggest that Humboldt squid are indirectly affected by
      OMZ shoaling through effects on a primary food source, myctophid fishes. Our
      results suggest that this indirect linkage between hypoxia and foraging is an
      important driver of the ongoing range expansion of Humboldt squid in the
      northeastern Pacific Ocean. 

PMID- 24443362
TI  - Editorial on "heat shock protein peptide complex-96 (HSPPC-96) vaccination for
      recurrent glioblastoma: a phase II, single arm trial".

PMID- 24443364
TI  - Evolution of postanesthesia care units: a legacy of politics, funding, and
      patient safety concerns.
AB  - Postanesthesia care units or PACUs (earlier called recovery rooms) flourished
      after World War II as social, political, and economic influences advanced
      enormous changes in health care expectations and delivery in the United States.
      Innovations in science and technology, facilitated by increased federal funding
      of scientific research in the years preceding and during the war, heralded a
      postwar need for greater complexity of hospital care safely delivered by trained
      personnel. PACUs began to open in new and modernized postwar hospitals as a means
      to safely provide more complex postoperative care during a time of persistent
      nursing shortages. PACUs proved to be an effective and cost-efficient means of
      decreasing the significantly high incidence of contemporary postoperative
      morbidity and mortality. Continuous and skilled observation by the recovery room
      nurses was credited with the improved patient outcomes. Once firmly established,
      PACUs have remained vital to the delivering of safe and cost-effective
      postoperative and postprocedural care. 

PMID- 24443365
TI  - The role of melanocortin 1 receptor in cutaneous malignant melanoma: along the
      mitogen-activated protein kinase pathway.
AB  - Cutaneous malignant melanoma (CMM) is an epidemic cancer in the United States.
      Survival rates for invasive CMM have not increased in past decades despite
      numerous clinical trials and the effective use of various combinations of
      chemotherapy agents to treat other cancers. Recent research has investigated the
      role of melanocortin 1 receptor (MC1R), a gene associated with red-hair phenotype
      in White individuals and with increased risk for developing CMM, in the mitogen
      activated protein kinase (MAPK) pathway. This limited narrative review discusses
      the incidence, history, and risk factors for CMM. It explores familial CMM and
      provides a brief review of melanocyte development and melanogenesis. Histology of
      CMM and cytogenetic techniques used to identify CMM mutations is also discussed.
      The structure and function of MC1R is described, with particular attention to
      MC1R's role in the MAPK pathway. Finally, the review touches on individualized
      therapy for CMM using genetic biomarkers and explores the promise of genomic
      research for finding effective treatments. 

PMID- 24443366
TI  - A large case-control study reveals a positive association between bisphosphonate
      use and delayed dental healing and osteonecrosis of the jaw.
AB  - This study sought to investigate, using a case-control study design, the
      association between bisphosphonate therapy and delayed dental healing and
      osteonecrosis of the jaw. Identification of potential cases of delayed dental
      healing was by consecutive screening of Specialist Oral and Maxillofacial and
      Special Needs Dentist clinic records for patients aged older than 50 years,
      during a 6-month window, in Victoria, Australia. Cases were confirmed by a case
      adjudication panel blinded to bisphosphonate status. Cases associated with
      malignancy or local radiotherapy were excluded. Controls were matched for age,
      sex, and source of dental referral (1:4, n = 160 controls). Variables of interest
      were dental precipitants, dental clinic type, smoking history, and medical
      comorbidities. A total of 4212 of 22,358 patients met inclusion criteria, of
      which 69 were potential cases with 40 (0.95%) confirmed cases. The odds ratio
      (OR) for developing delayed dental healing when taking an oral bisphosphonate was
      13.1 (95% confidence interval [CI] 4.4 to 39.3; p < 0.001). There were no cases
      associated with intravenous bisphosphonate use. There was some evidence of an
      interaction with age, sex, and clinic type. When adjusted for smoking, the
      estimated odds ratio was 11.6 (95% CI 1.9 to 69.4; p = 0.01). There was an
      association between having another illness and delayed dental healing (OR = 2.3;
      95% CI 1.0 to 5.2). A dental precipitant was present in 39 of 40 (97.5%) delayed
      dental healing cases. An important association between bisphosphonate use and
      delayed dental healing in the setting of benign bone disease, predominately in
      individuals with a dental precipitant, has been demonstrated.

PMID- 24443368
TI  - Exacerbation of BMI after cessation of growth hormone therapy in patients with
      Prader-Willi syndrome.
AB  - Long-term treatment with growth hormone (GH) in patients with Prader-Willi
      syndrome (PWS) improves not only height velocity, height standard deviation
      score, and final height, but also the degree of obesity and body composition
      abnormalities. Anecdotally, PWS patients tend to suffer from severe obesity and
      its complications after cessation of GH therapy. However, there have been no
      studies to investigate changes in body mass index (BMI) and adipose tissue
      distribution after cessation of GH therapy in young PWS patients. Therefore, we
      investigated changes in the BMI-standard deviation score (SDS) and adipose tissue
      distribution after cessation of GH therapy in PWS patients. We evaluated 14 PWS
      patients. BMI-SDS was calculated at 0, 6, 12, 18, and 24 months before and after
      cessation of GH treatment. We also evaluated subcutaneous adipose tissue (SAT)
      (cm(2)) and visceral adipose tissue (VAT) (cm(2)) area in 8 of the 14 study
      patients with single slice abdominal computed tomography at the level of the
      umbilicus. The BMI-SDS significantly increased at 6, 12, 18, and 24 months after
      cessation of GH therapy (P = 0.039, P = 0.008, P = 0.003, P = 0.003,
      respectively). There was a tendency toward increases in VAT at 12 and 24 months
      after cessation of GH therapy, but the increases did not reach statistical
      significance (P = 0.062, P = 0.125, respectively). Therefore, cessation of GH
      therapy in PWS patients worsened BMI. To maintain good body composition and
      prevent complications of obesity, long-term use of GH in adult PWS patients may
      be advisable.

PMID- 24443367
TI  - Is prostate cancer screening cost-effective? A microsimulation model of prostate
      specific antigen-based screening for British Columbia, Canada.
AB  - Prostate-specific antigen (PSA) screening for prostate cancer may reduce
      mortality, but it incurs considerable risk of over diagnosis and potential harm
      to quality of life. Our objective was to evaluate the cost-effectiveness of PSA
      screening, with and without adjustment for quality of life, for the British
      Columbia (BC) population. We adapted an existing natural history model using BC
      incidence, treatment, cost and mortality patterns. The modeled mortality benefit
      of screening derives from a stage-shift mechanism, assuming mortality reduction
      consistent with the European Study of Randomized Screening for Prostate Cancer.
      The model projected outcomes for 40-year-old men under 14 combinations of
      screening ages and frequencies. Cost and utility estimates were explored with
      deterministic sensitivity analysis. The incremental cost-effectiveness of regular
      screening ranged from $36,300/LYG, for screening every four years from ages 55 to
      69 years, to $588,300/LYG, for screening every two years from ages 40 to 74
      years. The marginal benefits of increasing screening frequency to 2 years or
      starting screening at age 40 years were small and came at significant cost. After
      utility adjustment, all screening strategies resulted in a loss of quality
      adjusted life years (QALYs); however, this result was very sensitive to utility
      estimates. Plausible outcomes under a range of screening strategies inform
      discussion of prostate cancer screening policy in BC and similar jurisdictions.
      Screening may be cost-effective, but the sensitivity of results to utility values
      suggests individual preferences for quality versus quantity of life should be a
      key consideration. 

PMID- 24443369
TI  - A stable scheme for a nonlinear, multiphase tumor growth model with an elastic
      membrane.
AB  - In this paper, we extend the 3D multispecies diffuse-interface model of the tumor
      growth, which was derived in Wise et al. (Three-dimensional multispecies
      nonlinear tumor growth-I: model and numerical method, J. Theor. Biol. 253 (2008)
      524-543), and incorporate the effect of a stiff membrane to model tumor growth in
      a confined microenvironment. We then develop accurate and efficient numerical
      methods to solve the model. When the membrane is endowed with a surface energy,
      the model is variational, and the numerical scheme, which involves adaptive mesh
      refinement and a nonlinear multigrid finite difference method, is demonstrably
      shown to be energy stable. Namely, in the absence of cell proliferation and
      death, the discrete energy is a nonincreasing function of time for any time and
      space steps. When a simplified model of membrane elastic energy is used, the
      resulting model is derived analogously to the surface energy case. However, the
      elastic energy model is actually nonvariational because certain coupling terms
      are neglected. Nevertheless, a very stable numerical scheme is developed
      following the strategy used in the surface energy case. 2D and 3D simulations are
      performed that demonstrate the accuracy of the algorithm and illustrate the shape
      instabilities and nonlinear effects of membrane elastic forces that may resist or
      enhance growth of the tumor. Compared with the standard Crank-Nicholson method,
      the time step can be up to 25 times larger using the new approach.

PMID- 24443370
TI  - Evaluation of the in vitro and in vivo biocompatibility of carrageenan-based
      hydrogels.
AB  - Carrageenans are highly sulphated galactans, well-known for their thermogelation
      properties which have been extensively exploited in food and cosmetics industry
      but poorly explored in the biomedicine field. In this study, we have assessed the
      in vitro and in vivo biocompatibility of kappa-carrageenan hydrogels that have
      been explored for regenerative medicine and tissue engineering applications. The
      in vitro cytotoxicity of the materials using a L929 mouse fibroblast cell line
      was evaluated, and the effect of kappa-carrageenan hydrogels on the activation of
      human polymorphonuclear neutrophils cells (hPMNs) was also evaluated by the
      quantification of reactive oxygen species by chemiluminescence. Subsequently, the
      inflammatory/immune reaction to kappa-carrageenan hydrogels on subcutaneous
      implantation was studied in rats. Explants were retrieved after 1 and 2 weeks of
      implantation for histological and RT-PCR analysis. The cytotoxicity screening
      revealed that kappa-carrageenan hydrogels did not significantly affect L929
      metabolic activity. Moreover, hPMNs contact with kappa-carrageenan resulted in a
      reduced and a neglectable signal regarding the detection of superoxide and
      hydroxyl anions, respectively. The results from the in vivo experiments indicated
      that kappa-carrageenan induce a low inflammatory response. Overall, the data
      obtained suggest that kappa-carrageenan hydrogels are biocompatible and thus can
      be further studied for their use in target biomedical applications.

PMID- 24443371
TI  - Differentiation of early first-trimester cranial neural tube defects.

PMID- 24443372
TI  - Resistance training restores muscle sex steroid hormone steroidogenesis in older
      men.
AB  - Skeletal muscle can synthesize testosterone and 5alpha-dihydrotestosterone (DHT)
      from dehydroepiandrosterone (DHEA) via steroidogenic enzymes in vitro, but
      hormone levels and steroidogenic enzyme expression decline with aging. Resistance
      exercise has been shown to increase in plasma sex steroid hormone levels.
      However, it remains unclear whether resistance training can restore impaired
      steroidogenic enzyme expressions in older individuals. Six young and 13 older men
      were recruited, and muscle biopsies were taken from the vastus lateralis at basal
      state. The same group of older subjects underwent resistance training involving
      knee extension and flexion exercises for 12 wk, and post-training biopsies were
      performed 4-5 d after the last exercise session. Muscular sex steroid hormone
      levels and sex steroidgenesis-related enzyme expressions were significantly lower
      in older subjects than younger ones at baseline, but 12 wk of resistance training
      significantly restored hormone levels (DHEA: 432+/-26 at baseline, 682+/-31
      pg/MUg protein, DHT: 6.2+/-0.9 at baseline, 9.8+/-1.4 pg/MUg protein).
      Furthermore, the steroidogenesis-related enzymes such as 3beta-hydroxysteroid
      dehydrogenase (HSD), 17beta-HSD, and 5alpha-reductase expressions were
      significantly restored by resistance training. We conclude progressive resistance
      training restores age-related declines in sex steroidogenic enzyme and muscle sex
      steroid hormone levels in older men.

PMID- 24443373
TI  - Adjunctive albuterol enhances the response to enzyme replacement therapy in late
      onset Pompe disease.
AB  - Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much
      higher than for other lysosomal storage disorders, which has been attributed to
      low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle.
      We have previously demonstrated the benefit of increased CI-MPR-mediated uptake
      of recombinant human acid-alpha-glucosidase during ERT in mice with Pompe disease
      following addition of albuterol therapy. Currently we have completed a pilot
      study of albuterol in patients with late-onset Pompe disease already on ERT for
      >2 yr, who were not improving further. The 6-min walk test (6MWT) distance
      increased in all 7 subjects at wk 6 (30+/-13 m; P=0.002), wk 12 (34+/-14 m;
      P=0.004), and wk 24 (42+/-37 m; P=0.02), in comparison with baseline. Grip
      strength was improved significantly for both hands at wk 12. Furthermore,
      individual subjects reported benefits; e.g., a female patient could stand up from
      sitting on the floor much more easily (time for supine to standing position
      decreased from 30 to 11 s), and a male patient could readily swing his legs out
      of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing).
      Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12
      (P=0.08), compared with baseline. With the exception of 1 patient who succumbed
      to respiratory complications of Pompe disease in the first week, only mild
      adverse events have been reported, including tremor, transient difficulty falling
      asleep, and mild urinary retention (requiring early morning voiding). Therefore,
      this pilot study revealed initial safety and efficacy in an open label study of
      adjunctive albuterol therapy in patients with late-onset Pompe disease who had
      been stable on ERT with no improvements noted over the previous several years.

PMID- 24443374
TI  - An in vivo model for analysis of developmental erythropoiesis and globin gene
      regulation.
AB  - Expression of fetal gamma-globin in adulthood ameliorates symptoms of beta
      hemoglobinopathies by compensating for the mutant beta-globin. Reactivation of
      the silenced gamma-globin gene is therefore of substantial clinical interest. To
      study the regulation of gamma-globin expression, we created the GG mice, which
      carry an intact 183-kb human beta-globin locus modified to express enhanced green
      fluorescent protein (eGFP) from the Ggamma-globin promoter. GG embryos express
      eGFP first in the yolk sac blood islands and then in the aorta-gonad mesonephros
      and the fetal liver, the sites of normal embryonic hematopoiesis. eGFP expression
      in erythroid cells peaks at E9.5 and then is rapidly silenced (>95%) and
      maintained at low levels into adulthood, demonstrating appropriate developmental
      regulation of the human beta-globin locus. In vitro knockdown of the epigenetic
      regulator DNA methyltransferase-1 in GG primary erythroid cells increases the
      proportion of eGFP(+) cells in culture from 41.9 to 74.1%. Furthermore, eGFP
      fluorescence is induced >3-fold after treatment of erythroid precursors with
      epigenetic drugs known to induce gamma-globin expression, demonstrating the
      suitability of the Ggamma-globin eGFP reporter for evaluation of gamma-globin
      inducers. The GG mouse model is therefore a valuable model system for genetic and
      pharmacologic studies of the regulation of the beta-globin locus and for
      discovery of novel therapies for the beta-hemoglobinopathies.

PMID- 24443375
TI  - Reply: To PMID 24242357.

PMID- 24443376
TI  - netClass: an R-package for network based, integrative biomarker signature
      discovery.
AB  - In the past years, there has been a growing interest in methods that incorporate
      network information into classification algorithms for biomarker signature
      discovery in personalized medicine. The general hope is that this way the typical
      low reproducibility of signatures, together with the difficulty to link them to
      biological knowledge, can be addressed. Complementary to these efforts, there is
      an increasing interest in integrating different data entities (e.g. gene and
      miRNA expressions) into comprehensive models. To our knowledge, R-package
      netClass is the first software that addresses both, network and data integration.
      Besides several published approaches for network integration, it specifically
      contains our recently published STSVM method, which allows for additional
      integration of gene and miRNA expression data into one predictive classifier.

PMID- 24443377
TI  - GR-Align: fast and flexible alignment of protein 3D structures using graphlet
      degree similarity.
AB  - MOTIVATION: Protein structure alignment is key for transferring information from
      well-studied proteins to less studied ones. Structural alignment identifies the
      most precise mapping of equivalent residues, as structures are more conserved
      during evolution than sequences. Among the methods for aligning protein
      structures, maximum Contact Map Overlap (CMO) has received sustained attention
      during the past decade. Yet, known algorithms exhibit modest performance and are
      not applicable for large-scale comparison. RESULTS: Graphlets are small induced
      subgraphs that are used to design sensitive topological similarity measures
      between nodes and networks. By generalizing graphlets to ordered graphs, we
      introduce GR-Align, a CMO heuristic that is suited for database searches. On the
      Proteus_300 set (44 850 protein domain pairs), GR-Align is several orders of
      magnitude faster than the state-of-the-art CMO solvers Apurva, MSVNS and
      AlEigen7, and its similarity score is in better agreement with the structural
      classification of proteins. On a large-scale experiment on the Gold-standard
      benchmark dataset (3 207 270 protein domain pairs), GR-Align is several orders of
      magnitude faster than the state-of-the-art protein structure comparison tools TM
      Align, DaliLite, MATT and Yakusa, while achieving similar classification
      performances. Finally, we illustrate the difference between GR-Align's flexible
      alignments and the traditional ones by querying a flexible protein in the Astral
      40 database (11 154 protein domains). In this experiment, GR-Align's top scoring
      alignments are not only in better agreement with structural classification of
      proteins, but also that they allow transferring more information across proteins.

PMID- 24443378
TI  - PhyloJIVE: Integrating biodiversity data with the Tree of Life.
AB  - MOTIVATION: Rich collections of biodiversity information such as spatial
      distributions, species descriptions and trait data are now synthesized in
      publicly available online sources such as GBIF. Also phylogenetic knowledge now
      provides a sound understanding of the origin of organisms and their place in the
      tree of life. We demonstrate with PhyloJIVE that any phylogenetic tree can be
      linked to online biodiversity data in the browser. This evolutionary view of
      biodiversity data is demonstrated in a case study that suggests that this
      approach may be useful to scientists and non-experts users.

PMID- 24443379
TI  - estMOI: estimating multiplicity of infection using parasite deep sequencing data.
AB  - Individuals living in endemic areas generally harbour multiple parasite strains.
      Multiplicity of infection (MOI) can be an indicator of immune status and
      transmission intensity. It has a potentially confounding effect on a number of
      population genetic analyses, which often assume isolates are clonal. Polymerase
      chain reaction-based approaches to estimate MOI can lack sensitivity. For
      example, in the human malaria parasite Plasmodium falciparum, genotyping of the
      merozoite surface protein (MSP1/2) genes is a standard method for assessing MOI,
      despite the apparent problem of underestimation. The availability of deep
      coverage data from massively parallizable sequencing technologies means that MOI
      can be detected genome wide by considering the abundance of heterozygous
      genotypes. Here, we present a method to estimate MOI, which considers unique
      combinations of polymorphisms from sequence reads. The method is implemented
      within the estMOI software. When applied to clinical P.falciparum isolates from
      three continents, we find that multiple infections are common, especially in
      regions with high transmission.

PMID- 24443380
TI  - Morpheus: a user-friendly modeling environment for multiscale and multicellular
      systems biology.
AB  - Morpheus is a modeling environment for the simulation and integration of cell
      based models with ordinary differential equations and reaction-diffusion systems.
      It allows rapid development of multiscale models in biological terms and
      mathematical expressions rather than programming code. Its graphical user
      interface supports the entire workflow from model construction and simulation to
      visualization, archiving and batch processing.

PMID- 24443381
TI  - Automatic identification of mixed bacterial species fingerprints in a MALDI-TOF
      mass-spectrum.
AB  - MOTIVATION: Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry has been broadly adopted by routine clinical microbiology
      laboratories for bacterial species identification. An isolated colony of the
      targeted microorganism is the single prerequisite. Currently, MS-based microbial
      identification directly from clinical specimens can not be routinely performed,
      as it raises two main challenges: (i) the nature of the sample itself may
      increase the level of technical variability and bring heterogeneity with respect
      to the reference database and (ii) the possibility of encountering polymicrobial
      samples that will yield a 'mixed' MS fingerprint. In this article, we introduce a
      new method to infer the composition of polymicrobial samples on the basis of a
      single mass spectrum. Our approach relies on a penalized non-negative linear
      regression framework making use of species-specific prototypes, which can be
      derived directly from the routine reference database of pure spectra. RESULTS: A
      large spectral dataset obtained from in vitro mono- and bi-microbial samples
      allowed us to evaluate the performance of the method in a comprehensive way.
      Provided that the reference matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry fingerprints were sufficiently distinct for the
      individual species, the method automatically predicted which bacterial species
      were present in the sample. Only few samples (5.3%) were misidentified, and bi
      microbial samples were correctly identified in up to 61.2% of the cases. This
      method could be used in routine clinical microbiology practice.

PMID- 24443382
TI  - Exploring genome characteristics and sequence quality without a reference.
AB  - MOTIVATION: The de novo assembly of large, complex genomes is a significant
      challenge with currently available DNA sequencing technology. While many de novo
      assembly software packages are available, comparatively little attention has been
      paid to assisting the user with the assembly. RESULTS: This article addresses the
      practical aspects of de novo assembly by introducing new ways to perform quality
      assessment on a collection of sequence reads. The software implementation
      calculates per-base error rates, paired-end fragment-size distributions and
      coverage metrics in the absence of a reference genome. Additionally, the software
      will estimate characteristics of the sequenced genome, such as repeat content and
      heterozygosity that are key determinants of assembly difficulty.

PMID- 24443383
TI  - ProbMetab: an R package for Bayesian probabilistic annotation of LC-MS-based
      metabolomics.
AB  - We present ProbMetab, an R package that promotes substantial improvement in
      automatic probabilistic liquid chromatography-mass spectrometry-based metabolome
      annotation. The inference engine core is based on a Bayesian model implemented to
      (i) allow diverse source of experimental data and metadata to be systematically
      incorporated into the model with alternative ways to calculate the likelihood
      function and (ii) allow sensitive selection of biologically meaningful
      biochemical reaction databases as Dirichlet-categorical prior distribution.
      Additionally, to ensure result interpretation by system biologists, we display
      the annotation in a network where observed mass peaks are connected if their
      candidate metabolites are substrate/product of known biochemical reactions. This
      graph can be overlaid with other graph-based analysis, such as partial
      correlation networks, in a visualization scheme exported to Cytoscape, with web
      and stand-alone versions.

PMID- 24443385
TI  - How "it gets better": effectively communicating support to targets of prejudice.
AB  - What is said when communicating intergroup support to targets of prejudice, and
      how do targets react? We hypothesized that people not targeted by prejudice
      reference social connection (e.g., social support) more than social change (e.g.,
      calling for a reduction in prejudice) in their supportive messages. However, we
      hypothesized that targets of prejudice would be more comforted by social change
      messages. We content coded naturalistic messages of support for lesbian, gay,
      bisexual, transgendered, and questioning teenagers from youtube.com (Study 1) and
      college undergraduates' statements (Study 2a) and found social connection
      messages more frequent than social change messages. Next, we explored targets'
      responses (Studies 2b-4b). Lesbian and gay participants rated social connection
      messages less comforting than social change messages (Study 3). Study 4 showed
      that only targets of prejudice distinguish social connection from social change
      messages in this way, versus non-targets. These results highlight the importance
      of studying the communication, content, and consequences of positive intergroup
      attitudes. 

PMID- 24443384
TI  - The potential economic benefits of improved postfracture care: a cost
      effectiveness analysis of a fracture liaison service in the US health-care
      system.
AB  - Fractures related to osteoporosis are associated with $20 billion in cost in the
      United States, with the majority of cost born by federal health-care programs,
      such as Medicare and Medicaid. Despite the proven fracture reduction benefits of
      several osteoporosis treatments, less than one-quarter of patients older than 65
      years of age who fracture receive such care. A postfracture liaison service (FLS)
      has been developed in many health systems but has not been widely implemented in
      the United States. We developed a Markov state-transition computer simulation
      model to assess the cost-effectiveness of an FLS using a health-care system
      perspective. Using the model, we projected the lifetime costs and benefits of
      FLS, with or without a bone mineral density test, in men and women who had
      experienced a hip fracture. We estimated the costs and benefits of an FLS, the
      probabilities of refracture while on osteoporosis treatment, as well as the
      utilities associated with various health states from published literature. We
      used multi-way sensitivity analyses to examine impact of uncertainty in input
      parameters on cost-effectiveness of FLS. The model estimates that an FLS would
      result in 153 fewer fractures (109 hip, 5 wrist, 21 spine, 17 other), 37.43 more
      quality-adjusted life years (QALYs), and save $66,879 compared with typical
      postfracture care per every 10,000 postfracture patients. Doubling the cost of
      the FLS resulted in an incremental cost-effectiveness ratio (ICER) of $22,993 per
      QALY. The sensitivity analyses showed that results were robust to plausible
      ranges of input parameters; assuming the least favorable values of each of the
      major input parameters results in an ICER of $112,877 per QALY. An FLS targeting
      patients post-hip fracture should result in cost savings and reduced fractures
      under most scenarios.

PMID- 24443386
TI  - SKP2 overexpression is associated with increased serine 10 phosphorylation of p27
      (pSer10p27) in triple-negative breast cancer.
AB  - S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator,
      targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is
      frequently overexpressed in breast cancer. p27 regulates G1 /S transition by
      abrogating the activity of cyclin/CDK complexes. p27 can undergo phosphorylation
      at serine 10 (pSer10p27). This phosphorylation event is associated with increased
      cell proliferation and poor prognosis in patients with glioma. The relationship
      between SKP2 and pSer10p27 in breast cancer has not been previously investigated.
      Immunohistochemistry (IHC) of SKP2, p27, pSer10p27, and other genes involved in
      this pathway, was analyzed in 188 breast tumors and 50 benign reduction
      mammoplasty samples. IHC showed SKP2 to be more highly expressed in estrogen
      receptor alpha (ERalpha)-negative breast cancers and demonstrated that triple
      negative tumors were more likely to have high expression of SKP2 than were non
      triple negative, ERalpha-negative tumors. A significant positive relationship was
      discovered for SKP2 and pSer10p27. High levels of SKP2 and pSer10p27 were
      observed significantly more often in ERalpha-negative and triple-negative than in
      ERalpha-positive breast cancers. Use of the triple-negative TMX2-28 breast cancer
      cell line to address the role of SKP2 in cell cycle progression confirmed that
      SKP2 contributes to a more rapid cell cycle progression and may regulates
      pSer10p27 levels. Together, the results indicate that presence of high SKP2 plus
      high pSer10p27 levels in triple-negative breast cancers is associated with
      aggressive growth, and highlight the validity of using SKP2 inhibitors as a
      therapeutic approach for treating this subset of breast cancers.

PMID- 24443387
TI  - Absence of skeletal anomalies in siblings with a maternally inherited 12q13.13
      q13.2 microdeletion partially involving the HOXC gene cluster.
AB  - Microdeletions (12q13.13-q13.2) involving the HOXC gene cluster are rare. Only
      three patients with this contiguous deletion have been reported, all resulting in
      phenotypic features that include skeletal anomalies, facial dysmorphism, and
      intellectual disability. The deletion of the HOXC gene cluster is thought to
      result in skeletal anomalies in these patients. We report on siblings with a 969
      kb deletion in the 12q13.13-q13.2 region detected by array comparative genomic
      hybridization (aCGH). This deletion spans seven of nine HOXC cluster genes. FISH
      analysis confirmed the siblings and mother were carriers of the 12q13.13-q13.2
      deletion. Although minor facial dysmorphic features were present in both
      siblings, no skeletal anomalies were present in the siblings or the mother. The
      proband had autistic-like features and mild developmental delay, while the
      sibling and mother are of normal intelligence. The absence of skeletal anomalies
      in our family suggests that deletion of the entire HOXC gene cluster may be
      required to result in an abnormal skeletal phenotype, or those skeletal anomalies
      in previously reported patients may be attributed to other genes within the
      deletion interval.

PMID- 24443389
TI  - Can febrile status cause hippocampal sclerosis?

PMID- 24443388
TI  - Bacterial community dynamics and activity in relation to dissolved organic matter
      availability during sea-ice formation in a mesocosm experiment.
AB  - The structure of sea-ice bacterial communities is frequently different from that
      in seawater. Bacterial entrainment in sea ice has been studied with traditional
      microbiological, bacterial abundance, and bacterial production methods. However,
      the dynamics of the changes in bacterial communities during the transition from
      open water to frozen sea ice is largely unknown. Given previous evidence that the
      nutritional status of the parent water may affect bacterial communities during
      ice formation, bacterial succession was studied in under ice water and sea ice in
      two series of mesocosms: the first containing seawater from the North Sea and the
      second containing seawater enriched with algal-derived dissolved organic matter
      (DOM). The composition and dynamics of bacterial communities were investigated
      with terminal restriction fragment length polymorphism (T-RFLP), and cloning
      alongside bacterial production (thymidine and leucine uptake) and abundance
      measurements (measured by flow cytometry). Enriched and active sea-ice bacterial
      communities developed in ice formed in both unenriched and DOM-enriched seawater
      (0-6 days). gamma-Proteobacteria dominated in the DOM-enriched samples,
      indicative of their capability for opportunistic growth in sea ice. The bacterial
      communities in the unenriched waters and ice consisted of the classes
      Flavobacteria, alpha- and gamma-Proteobacteria, which are frequently found in
      natural sea ice in polar regions. Furthermore, the results indicate that seawater
      bacterial communities are able to adapt rapidly to sudden environmental changes
      when facing considerable physicochemical stress such as the changes in
      temperature, salinity, nutrient status, and organic matter supply during ice
      formation. 

PMID- 24443390
TI  - Dairy food intake, peripheral bone structure, and muscle mass in elderly
      ambulatory women.
AB  - Previous studies suggest that dairy intake may be associated with reduced bone
      and muscle loss with aging, but there are limited data in the very old. We
      evaluated the association between intake of dairy foods and peripheral bone
      structure and muscle mass in 564 elderly women aged 80 to 92 (mean 84.7) years,
      who were participants of the Calcium Intake Fracture Outcome Study/CAIFOS Aged
      Extension Study (CAIFOS/CARES) cohort and attended the 10-year follow-up.
      Assessments included dairy consumption (milk, yogurt, and cheese) by a validated
      food frequency questionnaire, 15% tibia bone mass, area and volumetric bone
      mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), and
      appendicular bone and skeletal muscle mass by dual-energy X-ray absorptiometry
      (DXA). Women were categorized according to tertiles of dairy intake: first
      tertile (<= 1.5 servings/d), second tertile (1.5 to 2.2 servings/d) and third
      tertile (>= 2.2 servings/d). Controlling for confounding factors, pQCT assessment
      at the 15% tibia showed that compared with those in the first tertile of dairy
      intake, women in the third tertile had 5.7% greater total bone mass (p = 0.005),
      principally because of an increase in cortical and subcortical bone mass (5.9%, p
      = 0.050), resulting in a 6.2% increase in total vBMD (p = 0.013). Trabecular but
      not cortical and subcortical vBMD was also higher (7.8%, p = 0.044). DXA
      assessment showed that women in the third tertile of dairy intake had greater
      appendicular bone mass (7.1%, p = 0.007) and skeletal muscle mass (3.3%, p =
      0.014) compared with tertile 1. The associations with bone measures were
      dependent on dairy protein and calcium intakes, whereas the association with
      appendicular muscle mass was not totally dependent on dairy protein intake. Our
      results suggest a positive association of dairy intake with appendicular bone
      mineralization and muscle mass in elderly women. Because many fractures in this
      age group are of the appendicular skeleton often associated with falls, dairy
      intake may be a modifiable lifestyle factor contributing to healthy aging.

PMID- 24443391
TI  - Investigation of association of serotonin transporter and monoamine oxidase-A
      genes with Alzheimer's disease and depression in the VITA study cohort: a 90
      month longitudinal study.
AB  - Alzheimer's disease (AD) and depression (DE) are common psychiatric disorders
      strongly intertwined with one another. Nevertheless, etiology and early diagnosis
      of the disorders are still elusive. Several genetic variations have been
      suggested to associate with AD and DE, particularly in genes involved in the
      serotonergic system such as the serotonin transporter (SERT/SLC6A4), responsible
      for the removal from the synaptic cleft, and the monoamine-oxidase-A (MAOA),
      responsible for the presynaptic degradation of serotonin. Here, we attempt to
      characterize this pleiotropic effect for the triallelic SERT gene-linked
      polymorphic region (5HTTLPR) and for the MAOA-uVNTR, in participants in the
      Vienna-Transdanube-Aging (VITA)-study. The VITA-study is a community-based
      longitudinal study following a birth cohort (75 years old at baseline
      examination, n = 606) from Vienna for a period of 90 months with a regular follow
      up interval of 30 months. Our main finding, confirming previous reports, is that
      the 5HTTLPR S-allele is a risk allele for DE (OR = 1.55 CI 95% 1.03-2.32) and its
      carriers had a steeper increase in SGDS sum score. No association to AD was
      found. MAOA-uVNTR did not associate with either AD or DE. However, in AD MAOA
      uVNTR S-allele carriers a steeper increase of HAMD and STAI1 sum scores (P <
      0.05) was observed. Although the VITA-study cohort is rather small with low power
      to detect gene alterations, the uniqueness of this very thoroughly investigated
      and homogenous cohort strengthens the results through exceptional data
      collection. Still, reinvestigation in a larger cohort similar to this, as well as
      a meta-analysis, is important to confirm these results.

PMID- 24443392
TI  - Impact of maternal diet on neonatal anthropometry: a randomized controlled trial.
AB  - OBJECTIVE: Large for gestational age infants are at increased risk of childhood
      obesity and maternal nutrition impacts birthweight. The aim of this study was to
      assess the impact of a maternal low glycaemic index (GI) diet on neonatal
      anthropometry. METHODS: The ROLO (Randomised Control Trial of Low Glycaemic Index
      Diet in Pregnancy) study was a randomized controlled trial to assess the impact
      of a low GI diet versus usual diet on birthweight. It took place in a tertiary
      maternity hospital in Ireland and women were randomized to receive either a low
      GI diet or no dietary intervention from early pregnancy to term. Two hundred
      sixty-five neonates had anthropometric measurements on day 1-2 of life, 126 in
      the intervention group and 139 in the control group. Measurements included
      birthweight, length and circumferences of the head, chest, abdominal, thigh and
      mid-upper arm. A subgroup of 219 (82%) neonates also had skin-fold measurements.
      RESULTS: Neonates whose mothers had a low GI diet in pregnancy had lower thigh
      circumference (15.9 +/- 1.7 cm vs. 16.6 +/- 1.5 cm, P = 0.04). There was no
      difference between the intervention and control groups in head, chest abdominal
      or mid-upper arm circumferences. No difference was noted between the two groups
      for any skin-fold measurements (subscapular, thigh, biceps and triceps).
      CONCLUSION: Neonatal thigh circumference was altered by maternal low GI diet in
      pregnancy. These findings suggest that maternal low GI diet is safe in pregnancy
      and may positively impact infant adiposity.

PMID- 24443393
TI  - Increased risk of coronary heart disease in male patients with central serous
      chorioretinopathy: results of a population-based cohort study.

PMID- 24443394
TI  - Familial hemiplegic migraine treated by sodium valproate and lamotrigine.
AB  - BACKGROUND: Familial hemiplegic migraine (FHM) is a rare monogenic subtype of
      migraine with aura that includes motor auras. Prophylactic treatment of FHM often
      has marginal effects and involves a trial-and-error strategy based on therapeutic
      guidelines for non-hemiplegic migraine and on case reports in FHM. METHODS: We
      assessed the response to prophylactic medication in an FHM family and sequenced
      the FHM2 ATP1A2 gene in all available relatives. RESULTS: A novel p.Met731Val
      ATP1A2 mutation was identified. Attack frequency was reduced significantly with
      sodium valproate monotherapy (n = 1) and attacks ceased completely with a
      combination of sodium valproate and lamotrigine (n = 2). CONCLUSIONS: We report
      dramatic prophylactic effects of sodium valproate and lamotrigine in an FHM2
      family, making these drugs worth considering in the treatment of other FHM
      patients.

PMID- 24443395
TI  - Nutraceuticals in the prophylaxis of pediatric migraine: Evidence-based review
      and recommendations.
AB  - INTRODUCTION: The literature on complementary and alternative medicine (CAM) is
      expanding. One of the most common conditions for which CAM is studied in the
      pediatric population is migraine. Nutraceuticals are a form of CAM that is being
      used for pediatric migraine prophylaxis. METHODS: A literature search was carried
      out in order to identify both observational studies and randomized controlled
      trials on the use of nutraceuticals for the prophylaxis of pediatric migraine.
      Adult studies on included nutraceuticals were also reviewed. REVIEW: Thirty
      studies were reviewed on six different nutraceuticals: butterbur, riboflavin,
      ginkgolide B, magnesium, coenzyme Q10 and polyunsaturated fatty acids.
      CONCLUSION: Overall, the quality of the evidence for the use of nutraceuticals in
      pediatric migraine prophylaxis is poor. Further research needs to be done in
      order to study the efficacy of nutraceuticals for the prophylaxis of pediatric
      migraine.

PMID- 24443396
TI  - Brain mechanisms underlying reality monitoring for heard and imagined words.
AB  - Using functional MRI, we investigated reality monitoring for auditory
      information. During scanning, healthy young adults heard words in another
      person's voice and imagined hearing other words in that same voice. Later,
      outside the scanner, participants judged words as "heard," "imagined," or "new."
      An area of left middle frontal gyrus (Brodmann's area, or BA, 6) was more active
      at encoding for imagined items subsequently correctly called "imagined" than for
      items incorrectly called "heard." An area of left inferior frontal gyrus (BA 45,
      44) was more active at encoding for items subsequently called "heard" than
      "imagined," regardless of the actual source of the item. Scores on an Auditory
      Hallucination Experience Scale were positively related to activity in superior
      temporal gyrus (BA 22) for imagined words incorrectly called "heard." We suggest
      that activity in these areas reflects cognitive operations information (middle
      frontal gyrus) and semantic and perceptual detail (inferior frontal gyrus and
      superior temporal gyrus, respectively) used to make reality-monitoring
      attributions. 

PMID- 24443397
TI  - eComment. The effect of postoperative change in bronchial angle on postoperative
      pulmonary function after upper lobectomy in lung cancer patients.

PMID- 24443398
TI  - eComment. The role of the ispilateral hemidiaphragm following upper lobectomy.

PMID- 24443399
TI  - eComment. Cryoanalgesia in post-thoracotomy pain: efficiency and pain measurement
      methods.

PMID- 24443400
TI  - eComment. Initial workup and decision-making regarding coexistence of massive
      haemothorax and haemopericardium.

PMID- 24443401
TI  - eComment. Prompt decision making on the site of surgical approach in patients
      with chest trauma-a brief communication.

PMID- 24443404
TI  - The prevalence of colorectal adenomas in asymptomatic Korean men and women.
AB  - BACKGROUND: Colorectal cancer incidence is rapidly rising in many Asian
      countries, with rates approaching those of Western countries. This study aimed to
      evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk
      strata in asymptomatic Koreans. METHODS: Cross-sectional study of 19,372
      consecutive participants aged 20 to 79 years undergoing screening colonoscopy at
      the Center for Health Promotion of the Samsung Medical Center in Korea from
      January 2006 to June 2009. RESULTS: Among participants at average risk, those
      without a history of colorectal polyps or a family history of colorectal cancer,
      the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%,
      respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence
      of adenomas increased with age in both men and women, with a more marked increase
      for advanced adenoma. Participants with a family history of colorectal cancer or
      with a history of colorectal polyps had significantly higher prevalence of
      adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and
      sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The
      prevalence of adenomas increased annually in both men and women. CONCLUSIONS: In
      this large study of asymptomatic Korean men and women participating in a
      colonoscopy screening program, the prevalence of colorectal adenomas was
      comparable and possibly higher than previously reported in Western countries.
      IMPACT: Cost-effectiveness studies investigating the optimal age for starting
      colonoscopy screening and etiological studies to identify the reasons for the
      increasing trend in colorectal adenomas in Koreans are needed.

PMID- 24443403
TI  - Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast
      cancer in the nurses' health study II.
AB  - BACKGROUND: Evidence from the Nurses' Health Study II (NHSII) suggests that red
      meat consumption is associated with increased breast cancer risk in premenopausal
      women. Iron may be responsible by contributing to oxidative stress or effects on
      immune function. METHODS: We conducted a case-control study nested within the
      NHSII, examining prediagnostic plasma ferritin (n = 795 cases, 795 controls), 15
      hemochromatosis gene (HFE) single-nucleotide polymorphisms (SNP; n = 765 cases,
      1,368 controls), and breast cancer risk. Cases were diagnosed after providing
      blood samples between 1996 and 1999. ORs and 95% confidence intervals (CI) were
      calculated for ferritin levels by conditional logistic regression and for HFE
      SNPs by unconditional logistic regression. RESULTS: We did not observe a
      significant association between ferritin levels and breast cancer (top vs. bottom
      quartile multivariate OR: 1.05; 95% CI, 0.77-1.45; PTrend = 0.77). Results did
      not change when restricted to women who were premenopausal at blood draw, and
      were similar when cases were examined by hormone receptor status, and menopausal
      status at diagnosis. No HFE SNPs were significantly associated with breast cancer
      in a log-additive manner. Among controls, ferritin levels were nominally
      associated with SNPs rs9366637 (PTrend = 0.04), rs6918586 (PTrend = 0.06), and
      rs13161 (PTrend = 0.07), but results did not remain significant after adjusting
      for multiple testing. CONCLUSIONS: Ferritin levels and HFE SNPs were not
      associated with breast cancer risk in this population. IMPACT: Components of red
      meat other than iron are likely responsible for its positive association with
      breast cancer in premenopausal women.

PMID- 24443406
TI  - Ontario's ColonCancerCheck: results from canada's first province-wide colorectal
      cancer screening program.
AB  - BACKGROUND: ColonCancerCheck (CCC), Canada's first province-wide colorectal
      cancer screening program, was publicly launched in Ontario in April 2008. The
      objective of this article is to report on key indicators of CCC Program
      performance since its inception. METHODS: The CCC Program recommends biennial
      guaiac-based fecal occult blood test (gFOBT) for persons 50 to 74 years of age at
      average risk for colorectal cancer and colonoscopy for those at increased risk
      (having one or more first-degree relatives with a diagnosis of colorectal
      cancer). Opportunistic screening with colonoscopy is available in Ontario. Five
      data sources were used to compute indicators of program performance during 2008
      to 2011. The indicators computed were FOBT participation, overdue for screening,
      FOBT positivity, positive predictive value (PPV) of FOBT for colorectal cancer,
      diagnostic follow-up, and colorectal cancer detection rate. RESULTS: In 2011,
      FOBT participation was 29.8% and 46.8% of the target population was overdue for
      screening. FOBT positivity was higher among men (5.1%) than women (3.5%), and the
      PPV of FOBT for cancer was 4.3% in 2011. Follow-up colonoscopy within 6 months of
      a positive FOBT was completed by 74.6% of Program participants in 2011. The
      cancer detection rates for FOBT and for colonoscopy in those with a family
      history were 1.3 per 1,000 and 4.0 per 1,000, respectively, in 2011. CONCLUSION:
      These results provide an early indication of Program performance and provide
      findings relevant to other organized colorectal cancer screening programs.
      IMPACT: The greater cancer detection rate in those at increased risk due to
      family history who undergo colonoscopy screening suggests that a strategy of risk
      stratification will enhance the impact of FOBT-based screening programs.

PMID- 24443405
TI  - Oxidative balance score, colorectal adenoma, and markers of oxidative stress and
      inflammation.
AB  - BACKGROUND: An oxidative balance score (OBS) that combines pro- and antioxidant
      exposures was previously reported to be associated with incident sporadic
      colorectal adenoma. We extend the previous analyses by assessing associations of
      the OBS and colorectal adenoma with circulating biomarkers of oxidative stress
      [F2-isoprostanes (FIP) and fluorescent oxidation products (FOP)], and
      inflammation [C-reactive protein (CRP)]. METHODS: Using pooled data from two
      previously conducted colonoscopy-based case-control studies of incident, sporadic
      colorectal adenoma (n = 365), the OBS was constructed and divided into three
      approximately equal intervals, with the lowest interval used as the reference.
      Biomarker levels were dichotomized as "high" versus "low" based on the median
      values among controls. Multivariable logistic regression was used to calculate
      adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: For the
      OBS-adenoma association, the ORs (95% CIs) for the middle and highest (relative
      to the lowest) score intervals were 0.81 (0.46-1.43) and 0.39 (0.17-0.89),
      respectively. The corresponding OBS category-specific ORs (95% CIs) were 0.50
      (0.25-1.01) and 0.25 (0.10-0.65) for FIP, 2.01 (1.13-3.75) and 3.48 (1.51-8.02)
      for FOP, and 0.57 (0.31-1.04) and 0.21 (0.09-0.49) for CRP. The ORs (95% CIs)
      reflecting associations of adenoma with high levels of FIP, FOP, and CRP were
      1.89 (1.08-3.30), 1.82 (1.11-2.99), and 1.45 (0.88-2.40), respectively.
      CONCLUSIONS: As hypothesized, the OBS was inversely associated with colorectal
      adenoma and circulating FIP and CRP levels. The reason for the unexpected direct
      OBS-FOP association is unknown. IMPACT: These data support the use of combined
      measures of pro- and antioxidant exposures in studies of colorectal neoplasia.

PMID- 24443407
TI  - Electrographic seizures are associated with brain injury in newborns undergoing
      therapeutic hypothermia.
AB  - OBJECTIVE: Seizures are common among newborns with hypoxic-ischaemic
      encephalopathy (HIE) but the relationship between seizure burden and severity of
      brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is
      unclear. We tested the hypothesis that seizure burden is associated with cerebral
      tissue injury independent of amplitude-integrated EEG (aEEG) background activity.
      STUDY DESIGN: Term neonates undergoing 72 h of TH at four centres were selected
      for study if they had continuous aEEG and MRI. The aEEG with corresponding 2
      channel raw EEG (aEEG/EEG), was classified by severity of background and seizure
      burden; MR images were classified by the severity of tissue injury. RESULTS: Of
      85 neonates, 52% had seizures on aEEG/EEG. Overall, 35% had high seizure burden,
      49% had abnormal aEEG background in the first 24 h and 36% had severe injury on
      MRI. Seizures were most common on the first day, with significant recurrence
      during and after rewarming. Factors associated with severe injury on MRI were
      high seizure burden, poor aEEG background, 10 min Apgar and the need for more
      than one anticonvulsant. In multivariate logistic regression, high seizure burden
      was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to
      17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant.
      CONCLUSIONS: Electrographic seizure burden is associated with severity of brain
      injury on MRI in newborns with HIE undergoing TH, independent of degree of
      abnormality on aEEG background. Seizures are common during cooling, particularly
      on day 1, with a significant rebound on day 4.

PMID- 24443408
TI  - Noninvasive sorting of stem cell aggregates based on intrinsic markers.
AB  - Noninvasive biomarkers hold important potential for the characterization and
      purification of stem cells because the addition of exogenous labels, probes, or
      reporters, as well as the disruption of cell-cell and cell-extracellular matrix
      interactions, can unintentionally but dramatically alter stem cell state. We
      recently showed that intensity of the intrinsically fluorescent metabolite,
      nicotinamide adenine dinucleotide (NADH), fluctuates predictably with changes in
      stem cell viability and differentiation state. Here, we use multiphoton flow
      cytometry developed in our laboratory to rapidly and noninvasively characterize
      and purify populations of intact stem cell aggregates based on NADH intensity and
      assessed the differentiation capacity of sorted populations. We found removal of
      aggregates with NADH intensity indicative of cell death resulted in a remaining
      population of aggregates significantly more likely to produce beating
      cardiomyocytes (26% vs. 8%, P < 0.05). Similarly, we found isolation of stem cell
      aggregates with NADH intensity indicative of future cardiac differentiation gave
      rise to more aggregates with beating cardiomyocytes at later time points (50% vs.
      28%, P < 0.05). Further, coupling NADH intensity with gating based on size,
      enhances the enrichment for EBs capable of giving rise to cardiomyocytes (59% vs.
      27%, P < 0.05). Thus, we demonstrate that endogenous properties of cell
      aggregates, such as NADH and size, can serve as gating parameters for large
      particle sorting devices to purify populations of stem cells or their progeny in
      a noninvasive manner, leading the way for improved therapeutic applications.

PMID- 24443409
TI  - Bisphosphonates inhibit osteosarcoma-mediated osteolysis via attenuation of tumor
      expression of MCP-1 and RANKL.
AB  - Osteosarcoma is the most common primary malignant tumor of bone and accounts for
      around 50% of all primary skeletal malignancies. In addition to novel
      chemotherapies, there is a need for adjuvant therapies designed to inhibit
      osteosarcoma proliferation and tumor-induced osteolysis to attenuate tumor
      expansion and metastasis. As such, studies on the efficacy of bisphosphonates on
      human osteosarcoma are planned after feasibility studies determined that the
      bisphosphonate zoledronic acid (ZOL) can be safely combined with conventional
      chemotherapy. However, the molecular mechanisms responsible for, and means of
      inhibiting, osteosarcoma-induced osteolysis are largely unknown. We establish
      that osteosarcoma growth directly correlates with tumor-induced osteolysis and
      activation of osteoclasts in vivo. In vitro, tumor cells were determined to
      expresses surface, but not soluble, receptor activator of NF-kappaB ligand
      (RANKL) and stimulated osteoclastogenesis in a manner directly proportional to
      their malignant potential. In addition, an aggressive osteosarcoma cell line was
      shown to secrete monocyte chemoattractant protein-1 (MCP-1), resulting in robust
      monocyte migration. Because MCP-1 is a key cytokine for monocyte recruitment and
      surface-bound RANKL strongly supports local osteoclastogenesis, we suggest that
      high levels of these signaling molecules are associated with the aggressive
      potential of osteosarcoma. Consistent with these findings, abundant expression of
      RANKL/MCP-1 was observed in tumor in vivo, and MCP-1 plasma levels strongly
      correlated with tumor progression and osteolysis. ZOL administration directly
      attenuates osteosarcoma production of RANKL/MCP-1, reducing tumor-induced bone
      destruction. In vivo, these findings also correlated with significant reduction
      in osteosarcoma growth. ZOL attenuates tumor-induced osteolysis, not only through
      direct inhibition of osteoclasts, but also through direct actions on tumor
      expression of osteoclast activators. These data provide insight regarding the
      effect of ZOL on osteosarcoma essential for designing the planned upcoming
      prospective randomized trials to determine the efficacy of bisphosphonates on
      osteosarcoma in humans.

PMID- 24443410
TI  - Delivering colloidal nanoparticles to mammalian cells: a nano-bio interface
      perspective.
AB  - Understanding the behavior of multifunctional colloidal nanoparticles capable of
      biomolecular targeting remains a fascinating challenge in materials science with
      dramatic implications in view of a possible clinical translation. In several
      circumstances, assumptions on structure-activity relationships have failed in
      determining the expected responses of these complex systems in a biological
      environment. The present Review depicts the most recent advances about colloidal
      nanoparticles designed for use as tools for cellular nanobiotechnology, in
      particular, for the preferential transport through different target compartments,
      including cell membrane, cytoplasm, mitochondria, and nucleus. Besides the
      conventional entry mechanisms based on crossing the cellular membrane, an insight
      into modern physical approaches to quantitatively deliver nanomaterials inside
      cells, such as microinjection and electro-poration, is provided. Recent
      hypotheses on how the nanoparticle structure and functionalization may affect the
      interactions at the nano-bio interface, which in turn mediate the nanoparticle
      internalization routes, are highlighted. In addition, some hurdles when this
      small interface faces the physiological environment and how this phenomenon can
      turn into different unexpected responses, are discussed. Finally, possible future
      developments oriented to synergistically tailor biological and chemical
      properties of nanoconjugates to improve the control over nanoparticle transport,
      which could open new scenarios in the field of nanomedicine, are addressed. 

PMID- 24443411
TI  - Correlation of clot imaging with endovascular recanalization in internal carotid
      artery terminus occlusion.
AB  - BACKGROUND AND PURPOSE: In a swine stroke model we have previously demonstrated a
      high-intensity fluid attenuated inversion recovery (FLAIR) signal representing
      the erythrocyte component of the clot. We hypothesized that the intensity of the
      FLAIR clot signal in patients with acute stroke may predict the efficacy of
      recanalization by thrombectomy devices. In this study we compared the
      pretreatment FLAIR signal intensity of the clots in the distal internal carotid
      artery (ICA) and the degree of angiographic recanalization rate after mechanical
      thrombectomy. METHODS: 25 consecutive acute stroke patients with ICA terminus
      (ICA-T) occlusion diagnosed with MRI at the UCLA Medical Center between 2002 and
      2013 were retrospectively reviewed. The intensity of the FLAIR clot signal at the
      distal ICA was blindly compared with the angiographic recanalization status
      (successful recanalization defined as Thrombolysis In Cerebral Infarction (TICI)
      score of 2b-3) and non-successful recanalization as TICI score 0-2a) after
      endovascular treatment. Multivariate logistic regression analysis for successful
      recanalization was performed. RESULTS: Successful recanalization was achieved in
      40% of patients (10/25) and showed a significantly higher FLAIR intensity
      (p=0.014). The cut-off value for clot intensity on the FLAIR sequence to predict
      recanalization was 0.7952, with 70% sensitivity and 80% specificity (95% CI 0.59
      to 0.96) using a receiver operating characteristic curve. In multivariate
      logistic regression analysis, only a high FLAIR clot intensity (>0.7952) was
      associated with successful recanalization (OR 16.79; 95% CI 1.29 to 218.92;
      p=0.031). CONCLUSIONS: High signal intensity on FLAIR clot imaging may predict
      successful recanalization after endovascular therapy for ICA-T occlusion.

PMID- 24443412
TI  - Direct continuous measurement of draining vein pressure during Onyx embolization
      in a swine arteriovenous malformation model.
AB  - OBJECTIVE: Periprocedural intracranial hemorrhage secondary to intranidal flow
      redirection may develop after arteriovenous malformation (AVM) embolization. We
      hypothesized that continuous draining vein pressure monitoring may identify
      clinically relevant hemodynamic changes during devascularization. Our goal was to
      characterize the draining vein pressures in a swine rete mirabile AVM model
      during embolization with Onyx. METHODS: An acute swine AVM model was constructed
      in six animals. Baseline, transoperative and final AVM area measurements were
      used to determine the degree of AVM embolization. Continuous video recordings
      were captured at 10 s intervals of active embolization. Draining vein pressure,
      arterial feeder pressure and heart rate were continuously monitored. RESULTS: The
      baseline and post-embolization mean draining vein pressures were 49.8+/-17.2 and
      33.0+/-11.7 mm Hg (p=0.01), mean arterial pressures were 79.8+/-19.4 and 79.6+/
      25.2 mm Hg (p=0.94), mean transnidal pressures were 35.8+/-19.7 and 45.4+/-33.7
      mm Hg (p=0.37) and mean heart rates were 81.1+/-11.9 and 83.1+/-12.8 bpm
      (p=0.38), respectively. The draining vein pressure was averaged according to the
      degree of AVM embolization and represented as a relative change compared with the
      baseline draining vein pressure, and the slopes were found to decrease in all
      cases (p=0.02). In half of the animals the draining vein pressure decreased
      progressively as the AVM was embolized. In the remaining animals the venous
      pressure only started to decline after the AVM had been devascularized by > 50%.
      CONCLUSIONS: The draining vein pressure response during Onyx embolization in the
      swine AVM model is heterogeneous. Continuous draining vein pressure monitoring is
      feasible and may potentially identify clinically relevant hemodynamic changes
      during AVM embolization.

PMID- 24443413
TI  - Discharge disposition to skilled nursing facility after endovascular reperfusion
      therapy predicts a poor prognosis.
AB  - OBJECTIVE: We explore the impact of discharge disposition (independent
      rehabilitation facility (IRF) vs skilled nursing facility (SNF)) on 90 day
      outcomes in persons with stroke who received acute endovascular treatment.
      METHODS: Using a database from a single primary care stroke center, discharge
      disposition, National Institutes of Health Stroke Scale (NIHSS), Totaled Health
      Risks in Vascular Events (THRIVE), Houston Intra-Arterial Therapy 2 (HIAT-2), and
      Acute Physiology and Chronic Health Evaluation (APACHE II) scores, and successful
      reperfusion were obtained. Univariate analysis was performed to assess predictors
      of good clinical outcome, as defined by 90 day modified Rankin Scale (mRS) scores
      <=2. A binary logistic regression model was used to determine the impact of
      placement to an IRF versus an SNF on clinical outcomes. RESULTS: 147 subjects
      were included in the analysis with a mean age of 63+/-14 years and median NIHSS
      of 18 (IQR 14-21). Final infarct volumes, and modified APACHE II, THRIVE, and
      HIAT-2 scores were similar between those discharged to an IRF and those
      discharged to an SNF.However, their 90 day outcomes were significantly different,
      with far fewer patients at SNFs achieving good clinical outcomes (25% vs 46%;
      p=0.023). Disposition to SNF was significantly associated with a lower
      probability of achieving an mRS score of 0-2 at 90 days (OR = 0.337 (95% CI 0.12
      to 0.94); p<0.04). CONCLUSIONS: Subjects discharged to SNFs and IRFs after
      thrombectomy have similar medical and neurological severity at admission and
      similar final infarct volumes at discharge. Despite these similarities, patients
      discharged to an SNF had a significantly lower probability of achieving a good
      neurological outcome. These results have implications for future acute stroke
      trial design.

PMID- 24443414
TI  - ASPECTS decay during inter-facility transfer predicts patient outcomes in
      endovascular reperfusion for ischemic stroke: a unique assessment of dynamic
      physiologic change over time.
AB  - BACKGROUND: Pretreatment Alberta Stroke Program Early CT Scores (ASPECTS) is
      associated with clinical outcomes. The rate of decline between subsequent images,
      however, may be more predictive of outcomes as it integrates time and physiology.
      METHODS: A cohort of patients transferred from six primary stroke centers and
      treated with intra-arterial therapy (IAT) was retrospectively studied. Absolute
      ASPECTS decay was defined as ((ASPECTS First CT-ASPECTS Second CT)/hours elapsed
      between images). A logistic regression model was performed to determine if the
      rate of ASPECTS decay predicted good outcomes at 90 days (modified Rankin Scale
      score of 0-2). RESULTS: 106 patients with a mean age of 66+/-14 years and a
      median National Institutes of Health Stroke Scale score of 19 (IQR 15-23) were
      analyzed. Median time between initial CT at the outside hospital to repeat CT at
      our facility was 2.7 h (IQR 2.0-3.6). Patients with good outcomes had lower rates
      of absolute ASPECTS decay compared with those who did not (0.14+/-0.23 score/h vs
      0.49+/-0.39 score/h; p<0.001). In multivariable modeling, the absolute rate of
      ASPECTS decay (OR 0.043; 95% CI 0.004 to 0.471; p=0.01) was a stronger predictor
      of good patient outcome than static pretreatment ASPECTS obtained before IAT (OR
      0.64; 95% CI 0.38 to 1.04; p=0.075). In practical terms, every 1 unit increase in
      ASPECTS decline per hour correlates with a 23-fold lower probability of a good
      outcome. CONCLUSIONS: Patients with faster rates of ASPECTS decay during inter
      facility transfers are associated with worse clinical outcomes. This value may
      reflect the rate of physiological infarct expansion and thus serve as a tool in
      patient selection for IAT.

PMID- 24443415
TI  - Public health programs as surrogates for social action in Suriname, South
      America.
AB  - This paper addresses the merits of public health activism that advocates for
      social change in which health is the outcome of interest. We acknowledge that
      while efforts at the individual level are important, social network models
      consider the underlying mechanisms that lie outside the public health sector.
      This paper considers the inequitable health of Indigenous people who bear a
      disproportionate share of the negative health consequences due to economic
      development programs that follow an assimilation model. This paper discusses a
      combination of theoretical constructs to understand and solve the problems at
      hand. It concludes that while the attention paid to technological and behavioral
      solutions at the individual level yields important health outcomes, attention
      should also be paid to structural causes that address social, political and
      economic barriers to prevent disease, disability and premature death. 

PMID- 24443416
TI  - Diabetes barriers and self-care management: the patient perspective.
AB  - For those individuals diagnosed with diabetes, the challenge is how to cope and
      manage the many aspects of their lives. The aim of this qualitative synthesis was
      to evaluate research studies for findings and then synthesize patients'
      experiences within the context of diabetes self-care while facing daily barriers.
      A total of 95 findings from 21 studies were categorized via like themes. These
      themes were further analyzed and aggregated to represent an interpretive meta
      synthesis via a rigorous methodological protocol as described by Pearson,
      Robertson-Malt, and Rittinmeyer and the Joanna Briggs Institute. Meta-synthesized
      findings suggest that patients "avoid and hinder self-management" as well as
      "desire self-care and living life." Clinicians can improve interactions and
      potentiate understanding when the therapeutic approach is about the person living
      with diabetes as opposed to clinical control. 

PMID- 24443417
TI  - White Matter Integrity of Specific Dentato-Thalamo-Cortical Pathways is
      Associated with Learning Gains in Precise Movement Timing.
AB  - The dentato-thalamo-cortical tract (DTCT) connects the lateral cerebellum with
      contralateral motor and nonmotor areas, such as the primary motor cortex (M1),
      the ventral premotor cortex (PMv), and the dorsolateral prefrontal cortex
      (DLPFC). As the acquisition of precisely timed finger movements requires the
      interplay between these brain regions, the structural integrity of the underlying
      connections might explain variance in behavior. Diffusion tensor imaging was used
      to 1) reconstruct the DTCT connecting the dentate nucleus with M1, PMv, and DLPFC
      and 2) examine to which extent their microstructural integrity (tract-related
      fractional anisotropy) relates to learning gains in a motor-sequence learning
      paradigm consisting of a synchronization and continuation part. Continuous DTCT
      were reconstructed from the dentate nucleus to all cortical target areas. We
      found that the microstructural integrity of the DTCT connecting the left dentate
      nucleus with the right DLPFC was associated with better early consolidation in
      rhythm continuation (R = -0.69, P = 0.02). The present data further advances the
      knowledge about a right-hemispheric timing network in the human brain with the
      DLPFC as an important node contributing to learning gains in precise movement
      timing. 

PMID- 24443418
TI  - Basophil activation after nonsteroidal anti-inflammatory drugs stimulation in
      patients with immediate hypersensitivity reactions to these drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently
      involved in allergic reactions of which two main types exist: IgE-mediated and
      crossintolerance. The diagnosis of crossintolerance reactions is often based on
      the drug provocation test. The potential value of the basophil activation test
      (BAT) was evaluated using different basophil markers in the diagnosis of patients
      with crossintolerance to NSAIDs and cutaneous symptoms. We studied 46 patients
      with crossintolerance to NSAIDs and 45 tolerant controls. BAT was performed with
      acetyl salicylic acid, paracetamol, diclofenac, dipyrone, naproxen, and ibuprofen
      at four different concentrations using CD193 and CD203c as basophil markers and
      CD63 as activation marker. We compared BAT results using CD193+ or CD193+ CD203c+
      for basophil selection and found a significant increase in the stimulation index
      when using CD193+ CD203c+ in both patients and controls (P = 0.004 and P = 0.017,
      respectively). Selection of living cells only produced an increase in basophil
      stimulation in patients for both CD193+ and CD193+ CD203c+ (P < 0.001 for both),
      whereas in controls there was no change with CD193+ and a decrease with CD193+
      CD203c+ (P = 0.001). We found that CD193+ CD203c+ increased the percentage of
      positive cases in patients and controls when compared with CD193+. When excluding
      dead cells, there was an increase of 21.7% in patients and 10% in controls. These
      results indicate that using CD193+ CD203+, excluding dead cells, is the best
      approach for BAT although this test is not recommended for the diagnosis of
      patients with crossintolerance to NSAIDs owing to its low sensitivity and
      specificity.

PMID- 24443419
TI  - Early divergence, broad distribution, and high diversity of animal chitin
      synthases.
AB  - Even though chitin is one of the most abundant biopolymers in nature, current
      knowledge on chitin formation is largely based only on data from fungi and
      insects. This study reveals unanticipated broad taxonomic distribution and
      extensive diversification of chitin synthases (CSs) in Metazoa, shedding new
      light on the relevance of chitin in animals and suggesting unforeseen complexity
      of chitin synthesis in many groups. We uncovered robust orthologs to insect type
      CSs in several representatives of deuterostomes, which generally are not thought
      to possess chitin. This suggests a broader distribution and function of chitin in
      this branch of the animal kingdom. We characterize a new CS type present not only
      in basal metazoans such as sponges and cnidarians but also in several bilaterian
      representatives. The most extensive diversification of CSs took place during
      emergence of lophotrochozoans, the third large group of protostomes next to
      arthropods and nematodes, resulting in coexistence of up to ten CS paralogs in
      molluscs. Independent fusion to different kinds of myosin motor domains in fungi
      and lophotrochozoans points toward high relevance of CS interaction with the
      cytoskeleton for fine-tuned chitin secretion. Given the fundamental role that
      chitin plays in the morphology of many animals, the here presented CS
      diversification reveals many evolutionary complexities. Our findings strongly
      suggest a very broad and multifarious occurrence of chitin and question an
      ancestral role as cuticular component. The molecular mechanisms underlying
      regulation of animal chitin synthesis are most likely far more complex and
      diverse than existing data from insects suggest. 

PMID- 24443422
TI  - A case of a patient with hyperosmolar hyperglycemic state: implications for nurse
      practitioners in primary care.
AB  - PURPOSE: The purpose of this case study is twofold: first, to present the
      pathophysiology of hyperosmolar hyperglycemic state (HHS) as it relates to a
      hospitalized patient with undiagnosed diabetes; the second is to increase
      awareness among primary care nurse practitioners (NPs) about the complexities of
      diagnosing less typical forms of diabetes. The case illustrates how HHS can be
      life threatening, how it is differentiated from diabetic ketoacidosis (DKA), and
      how it is treated. The importance of closer surveillance of blood glucose in high
      risk individuals is highlighted. DATA SOURCES: Review of the literature and
      application to the case. CONCLUSIONS: HHS is a potentially lethal and preventable
      hyperglycemic crisis, which is in a continuum with DKA, occurring frequently in
      individuals with no prior diagnosis of diabetes. The incidence of HHS is
      increasing as the epidemic of diabetes continues. It is important for NPs to
      understand the pathophysiology of HHS, and identify which patients are at risk.
      Many high-risk patients, when under stress, develop acute hyperglycemic crisis,
      which begets further cardiovascular complications. IMPLICATIONS FOR PRACTICE:
      With improved understanding of the phenomena leading to glucose dysregulation,
      less typical forms of diabetes might be identified earlier and controlled. NPs in
      primary care are uniquely positioned to reduce the risk of hyperglycemic crises.

PMID- 24443421
TI  - On-going palliative care enhances perceived control and patient activation and
      reduces symptom distress in patients with symptomatic heart failure: a pilot
      study.
AB  - INTRODUCTION: There is a paucity of research about the impact of palliative care
      (PC) on perceived control (i.e. one's perceived influence over outcomes or events
      in the environment) and activation (i.e. ability to self-manage) in patients with
      symptomatic heart failure (HF). Likewise, little is known about the association
      between perceived control, activation, and symptom distress in this patient
      population. We hypothesized that patients with advanced HF who received ongoing
      PC services (i.e. >=2 PC consultations) vs no access or a single PC consultation
      would have greater improvements in perceived control and activation and greater
      reductions in symptom distress three months post-discharge for HF exacerbation.
      METHODS: Forty-two patients (average age 53.9+/-8.0 years; predominantly male
      (72%), White (61%) and married (69%)) participated in the study. However, only 36
      (85.7%) patients completed an outpatient PC consultation of which 29 (69%)
      patients returned for additional follow-up visits with the PC team. Data on
      perceived control, activation, and symptom distress were collected at baseline
      and three months. Parametric statistical models were applied to draw conclusions.
      RESULTS: Findings showed that the patients who received >=2 PC consultations had
      greater improvements in perceived control and activation than their counterparts;
      these increases were associated with greater reductions in symptom distress.
      CONCLUSION: Our findings suggest that on-going PC interventions enhance perceived
      control and activation in patients with advanced HF and open up the possibility
      of planning larger studies to assess the effect of PC on these variables as
      possible mediators to improvements in self-management and clinical outcomes.

PMID- 24443423
TI  - Comparative neuroanatomy of the antennal lobes of 2 homopteran species.
AB  - We compared the morphology of the primary olfactory center, the antennal lobe
      (AL), in 2 homopteran insects, Hyalesthes obsoletus Signoret (Homoptera:
      Cixiidae) and Scaphoideus titanus Ball (Homoptera: Cicadomorpha). The comparison
      between the ALs of the 2 species is particularly interesting considering that,
      although both use volatile cues to locate their host plants, their feeding
      behavior differs considerably: specifically, H. obsoletus is a highly polyphagous
      species, whereas S. titanus is strictly monophagous (on grapevine). Our
      investigation of the AL structure using immunocytochemical staining and antennal
      backfills did not reveal any sexual dimorphism in either the size of the ALs or
      in the size of individual glomeruli for either species. Instead, the AL of H.
      obsoletus displayed numerous and well-delineated glomeruli (about 130 in both
      sexes) arranged in a multilayered structure, whereas the smaller AL of S. titanus
      contained fewer than 15 glomerular-like structures. This difference is likely to
      reflect the comparatively reduced olfactory abilities in S. titanus, probably as
      a consequence of the reduced number of volatiles coming from the single host
      plant. Instead, in H. obsoletus, the ability to distinguish among several host
      plants may require a more complex olfactory neuronal network. 

PMID- 24443420
TI  - Role of extracellular matrix signaling cues in modulating cell fate commitment
      for cardiovascular tissue engineering.
AB  - It is generally agreed that engineered cardiovascular tissues require cellular
      interactions with the local milieu. Within the microenvironment, the
      extracellular matrix (ECM) is an important support structure that provides
      dynamic signaling cues in part through its chemical, physical, and mechanical
      properties. In response to ECM factors, cells activate biochemical and
      mechanotransduction pathways that modulate their survival, growth, migration,
      differentiation, and function. This Review describes the role of ECM chemical
      composition, spatial patterning, and mechanical stimulation in the specification
      of cardiovascular lineages, with a focus on stem cell differentiation, direct
      transdifferentiation, and endothelial-to-mesenchymal transition. The
      translational application of ECMs is discussed in the context of cardiovascular
      tissue engineering and regenerative medicine.

PMID- 24443424
TI  - Baseline bone mineral density and boneturnover in pre-operative hip and knee
      arthroplasty patients.
AB  - AIMS: Osteoporosis and abnormal bone metabolism may prove to be significant
      factors influencing the outcome of arthroplasty surgery, predisposing to
      complications of aseptic loosening and peri-prosthetic fracture. We aimed to
      investigate baseline bone mineral density (BMD) and bone turnover in patients
      about to undergo arthroplasty of the hip and knee. METHODS: We prospectively
      measured bone mineral density of the hip and lumbar spine using dual-energy X-ray
      absorptiometry (DEXA) scans in a cohort of 194 patients awaiting hip or knee
      arthroplasty. We also assessed bone turnover using urinary deoxypyridinoline
      (DPD), a type I collagen crosslink, normalised to creatinine. RESULTS: The
      prevalence of DEXA proven hip osteoporosis (T-score <= -2.5) among hip and knee
      arthroplasty patients was found to be low at 2.8% (4 of 143). Spinal osteoporosis
      prevalence was higher at 6.9% (12 of 175). Sixty patients (42% (60 of 143)) had
      osteopenia or osteoporosis of either the hip or spine. The mean T-score for the
      hip was -0.34 (sd 1.23), which is within normal limits, and the mean hip Z-score
      was positive at 0.87 (sd 1.17), signifying higher-than-average BMD for age. The
      median urinary DPD/creatinine was raised in both female patients at 8.1
      (interquartile range (IQR) 6.6 to 9.9) and male patients at 6.2 (IQR 4.8 to 7.5).
      CONCLUSIONS: Our results indicate hip and knee arthroplasty patients have higher
      BMD of the hip and spine compared with an age-matched general population, and a
      lower prevalence of osteoporosis. However, untreated osteoporotic patients are
      undergoing arthroplasty, which may negatively impact their outcome. Raised DPD
      levels suggest abnormal bone turnover, requiring further investigation. Cite this
      article: Bone Joint Res 2014;3:14-19.

PMID- 24443425
TI  - New lignans and their biological activities.
AB  - Lignans, which are widely distributed in higher plants, represent a vast and
      rather diverse group of phenylpropane derivatives. They have attracted
      considerable attention due to their pharmacological activities. Some of the
      lignans have been developed approved therapeutics, and others are considered as
      lead structures for new drugs. This article is based on our previous review of
      lignans discovered in the period 2000-2004, and it provides a comprehensive
      compilation of the 354 new naturally occurring lignans obtained from 61 plant
      families between 2005 and 2011. We classified five main types according to their
      structural features, and provided the details of their sources, some typical
      structures, and diverse biological activities. A tabular compilation of the novel
      lignans by species is presented at the end. A total of 144 references were
      considered for this review. 

PMID- 24443426
TI  - Chemical constituents and biological activities of plants from the genus
      Neolitsea.

PMID- 24443427
TI  - Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis,
      and their melanogenesis-inhibitory and cytotoxic activities.
AB  - A new limonoid, 7-O-acetyl-7-O-debenzoyl-22-hydroxy-21-methoxylimocinin (2), and
      two new flavonoids, 3'-(3-hydroxy-3-methylbutyl)naringenin (7) and 4'-O
      methyllespedezaflavanone C (9), along with nine known compounds, including two
      limonoids, 1 and 3, and seven flavonoids, 4-6, 8, and 10-12, were isolated from a
      MeOH extract of the flowers of Azadirachta indica A.Juss. var. siamensis Valeton
      (Siamese neem tree; Meliaceae). The structures of new compounds were elucidated
      on the basis of extensive spectroscopic analysis and comparison with literature
      data. All of these compounds were evaluated for their melanogenesis-inhibitory
      activities in B16 melanoma cells induced with alpha-melanocyte-stimulating
      hormone (alpha-MSH). Compound 2 (16.9% melanin content at 30 MUM), 6
      deacetylnimbin (3; 49.6% melanin content at 100 MUM), and kaempferide (10; 41.7%
      melanin content at 10 MUM) exhibited inhibitory effects with no, or almost no,
      toxicity to the cells (81.0-111.7% cell viability). In addition, evaluation of
      their cytotoxic activities against HL60, A549, AZ521, and SK-BR-3 human cancer
      cell lines, isoazadironolide (1), 4'-O-methyl-8-prenylnaringenin (5),
      euchrestaflavanone A (8), 9, and 3-methoxy-3'-prenylnaringenin (12) revealed
      potent cytotoxicities against one or more cell lines with IC50 values in the
      range of 4.5-9.9 MUM. 

PMID- 24443428
TI  - Four ardeemin analogs from endophytic Aspergillus fumigatus SPS-02 and their
      reversal effects on multidrug-resistant tumor cells.
AB  - Four ardeemin derivatives, 5-N-acetylardeemin (1), 5-N-acetyl-15bbeta
      hydroxyardeemin (2), 5-N-acetyl-15b-didehydroardeemin (3), and 5-N-acetyl-16alpha
      hydroxyardeemin (4), were isolated from the fermentation broth of an endophytic
      Aspergillus fumigatus SPS-02 associated with Artemisia annua L. The structures of
      these metabolites were elucidated by a combination of spectroscopic data,
      including 1D-, 2D-NMR and MS. In vitro chemosensitization assay indicated that
      these ardeemins had different activities of reversing the multidrug-resistant
      (MDR) phenotype in three cancer cell lines, leukemia doxorubicin resistant cell
      K562/DOX, human lung adenocarcinoma cis-platin-resistant cell A549/DDP, and
      ovarian cancer cisplatin-resistant cell SK-OV-S/DDP. Compound 4 exhibited the
      strongest MDR reversing effect at 5 MUM concentration in K562/DOX and A549/DDP
      cell lines 5.2+/-0.18-fold, 8.2+/-0.23-fold, respectively, while compound 2 had
      the highest reversal capacity in SK-OV-S/DDP cell line with 10.8+/-0.28 fold.
      Preliminary investigation of their structure?activity relationship suggested that
      a OH group at C(15b) or C(16) in ardeemin plays a key role in reversing the MDR
      effect. It is the first report on ardeemin analogs from endophytic A. fumigatus
      with reversal effects on MDR cancer cell lines K562/DOX, A549/DDP and SK-OV
      S/DDP. 

PMID- 24443429
TI  - Isolation and characterization of antimicrobial cyclic dipeptides from
      Pseudomonas fluorescens and their efficacy on sorghum grain mold fungi.
AB  - This study was aimed at isolation and characterization of natural antifungal
      compounds for grain mold, a key parasitic fungal disease of sorghum. Pseudomonas
      fluorescens strain isolated from rhizosphere of groundnut crop was selected as a
      source. Its biocontrolling ability was assessed by testing some biochemical
      attributes such as phosphate-solubilization, and HCN, NH3 , indole-3-acetic acid,
      and siderophore production. The strain showed positive result for all except
      indole-3-acetic acid, revealing its suitability for a further study. The
      antibiotic-sensitivity pattern of the strain against 43 antibiotics was also
      established, which showed resistance to 15 antibiotics. The efficacy of P.
      fluorescens strain against grain mold was identified by dual culture technique.
      Hundred percent inhibition was found against Fusarium moniliforme, an important
      causative agent of this disease. The strain was fermented for secondary
      metabolites and extracted with AcOEt. Chromatographic separation of the extract
      yielded four known compounds, cyclo(L-Pro-L-Phe) (1), cyclo(trans-4-hydroxy-L-Pro
      L-Leu) (2), cyclo(trans-4-hydroxy-L-Pro-L-Phe) (3), and cyclo(Gly-L-Pro) (4),
      which were characterized by spectral analysis and optical rotation. The crude
      extract, a mixture of 2 and 3, and isolated 1 were proved to be significantly
      effective against grain mold fungi. This is the first report on production of
      these cyclic dipeptides by P. fluorescens and their antagonistic properties. 

PMID- 24443430
TI  - Chemotype diversity of indigenous Dalmatian sage (Salvia officinalis L.)
      populations in Montenegro.
AB  - To identify how many chemotypes of Salvia officinalis exist in Montenegro, the
      chemical composition of the essential oils of 12 wild-growing populations was
      determined by GC-FID and GC/MS analyses. Among the 40 identified constituents,
      the most abundant were cis-thujone (16.98-40.35%), camphor (12.75-35.37%), 1,8
      cineol (6.40-12.06%), trans-thujone (1.5-10.35%), camphene (2.26-9.97%), borneol
      (0.97-8.81%), viridiflorol (3.46-7.8%), limonene (1.8-6.47%), alpha-pinene (1.59
      5.46%), and alpha-humulene (1.77-5.02%). The composition of the essential oils
      under study did not meet the ISO 9909 requirements, while the oils of populations
      P02-P04, P09, and P10 complied with the German Drug Codex. A few of the main
      essential-oil constituents appeared to be highly intercorrelated. Strong positive
      correlations were observed between alpha-pinene and camphene, camphene and
      camphor, as well as between cis-thujone and trans-thujone. Strong negative
      correlations were evidenced between cis-thujone and alpha-pinene, cis-thujone and
      champhene, cis-thujone and camphor, as well as between trans-thujone and
      camphene. Multivariate analyses allowed the grouping of the populations into
      three distinct chemotypes, i.e., Chemotype A, rich in total thujones, Chemotype
      B, with intermediate contents of thujones, alpha-pinene, camphene, and camphor
      and high borneol contents, and Chemotype C, rich in camphor, camphene, and alpha
      pinene. The chemotypes did not significantly differ in the total essential-oil
      content and the cis/trans-thujone ratio. 

PMID- 24443431
TI  - Novel oxaliplatin derivatives with 1-(substituted benzyl)azetidine-3,3
      dicarboxylate anions. Synthesis, cytotoxicity, and interaction with DNA.
AB  - A series of oxaliplatin derivatives with (1R,2R)-N(1) -alkyl-1,2-cyclohexane-1,2
      diamine (alkyl=Bu or (i) Pr) as carrier ligands and 1-(methoxy- or methyl
      substituted benzyl)azetidine-3,3-dicarboxylate anions as leaving groups were
      synthesized and spectrally characterized. Generally, Complexes 10-15 with an (i)
      Pr substituent at N(1) showed higher activities in vitro than carboplatin against
      MCF-7 human breast carcinoma and A549 human non-small-cell lung cell lines,
      although they were less potent than oxaliplatin. The typical complex 14 exhibited
      cytotoxicity superior to that of carboplatin and comparable to that of
      oxaliplatin against two selected tumor cell lines. Additionally, agarose gel
      electrophoresis was applied to investigate the DNA-cleavage ability of complex
      14, which demonstrated that it has a different mode of DNA distortion from that
      of oxaliplatin. 

PMID- 24443432
TI  - Rare bisindole alkaloids from the Amazonian tree Raputia simulans.
AB  - The stem bark of Raputia simulans (Rutaceae) has been reported to contain simple
      and dimeric indole alkaloids. Further phytochemical investigation of R. simulans
      stem bark resulted in the isolation of three new alkaloids. These compounds
      represent a relatively new category of dimeric indole alkaloids with a
      cyclohexene moiety in their core. Their structure elucidations were based on NMR
      and HR-MS techniques, while structural aspects concerning their relative
      configuration were investigated using molecular mechanics calculations and NOESY
      experiments. 

PMID- 24443433
TI  - Cytotoxic polyphenols from a sponge-associated fungus Aspergillus versicolor Hmp
      48.
AB  - A new dibenzo[1,4]dioxin 1, and two new prenylated diphenyl ethers, 2 and 3,
      together with six known compounds, 4-9, were isolated from a sponge-associated
      fungus Aspergillus versicolor Hmp-F48 by bioactivity-guided fractionation. Their
      structures were elucidated by 1D- and 2D-NMR, and MS analyses. The compounds
      showed potent cell growth inhibitory activities against HL-60 cell line. 

PMID- 24443434
TI  - Chemical and biological evaluation of Hypericum maculatum Crantz essential oil.
AB  - The chemical composition and the antimicrobial activity of the essential oil
      isolated from the aerial parts of Hypericum maculatum Crantz were determined. In
      total, 109 compounds were identified, with germacrene D (21.5%), nonane (6.5%),
      (E)-beta-farnesene (5.3%), delta-cadinene (4.5%), and ledol (4.4%) as the main
      constituents. The chemical compositions of this oil and of four previously
      studied H. maculatum oils were compared using multivariate statistical analyses,
      viz., agglomerative hierarchical cluster and principal component analyses. Based
      on the results, the interrelationship among the hitherto studied H. maculatum oil
      samples, including the oil characterized here, was discussed. The study of the
      antimicrobial potential of the oil against five bacterial and two fungal strains
      showed that the oil had mainly moderate antimicrobial effects. 

PMID- 24443435
TI  - Chemical composition and biological activities of Tunisian Cupressus arizonica
      Greene essential oils.
AB  - The chemical composition of the essential oils obtained by hydrodistillation of
      leaves, stems, and female cones of Cupressus arizonica Greene, grown in Tunisia,
      was studied by GC-FID and GC/MS analyses. Altogether, 62 compounds were
      identified, 62 in the leaf oil, 19 in the cone oil, and 24 in the stem oil. The
      cone and stem oils were mainly composed by monoterpene hydrocarbons (96.6 and
      85.2%, resp.). In the leaf oil, the total sesquiterpene fraction constituted
      36.1% and that of the monoterpene hydrocarbons 33.8% of the total oil
      composition. The three oils were evaluated for their in vitro herbicidal activity
      by determining their influence on the germination and the shoot and root growth
      of the four weed species Sinapis arvensis L., Lolium rigidum Gaudin, Trifolium
      campestre Schreb., and Phalaris canariensis L. At the highest doses tested (0.8
      and 1.0 mg/ml), the leaf essential oil inhibited either totally or almost
      completely the seed germination and the shoot and root growth of S. arvensis and
      T. campestre. The oils were also tested for their antifungal activity; however,
      their effects on the fungal growth were statistically not significant. 

PMID- 24443436
TI  - In vitro biological activities of seed essential oils from the Cameroonian spices
      Afrostyrax lepidophyllus MILDBR. and Scorodophloeus zenkeri HARMS rich in sulfur
      containing compounds.
AB  - The chemical composition of the essential oils obtained from the seeds of bush
      onion (Afrostyrax lepidophyllus) and tropical garlic tree (Scorodophloeus
      zenkeri), plants used as spices in the traditional African cuisine, was
      determined by GC-FID and GC/MS analyses. Moreover, in vitro biological properties
      of the oils, namely, the cytotoxic, antioxidant, and antimicrobial activities,
      were investigated by the MTT, the DPPH(.) and ABTS(.+) scavenging, and the agar
      disc-diffusion methods, respectively. Both oils were composed mainly by S
      containing compounds, accounting for 91.0-96.1% of the total oil compositions,
      which provided them the typical garlic- and onion-like odors of spices. The
      predominant compound in both oils, 2,4,5,7-tetrathiaoctane (1; 51.5-52.9%), was
      isolated by preparative TLC and structurally elucidated by (1) H- and (13) C-NMR
      data. The oils exhibited a strong inhibitory effect on the growth of human cancer
      cells, namely, T98G (human glioblastoma multiforme cell line), MDA-MB 231 (human
      breast adenocarcinoma cell line), A375 (human malignant melanoma cell line), and
      HCT116 (human colon carcinoma cell line) cells, and a good DPPH(.) - and ABTS(.+)
      -scavenging activity, while the antimicrobial effects were negligible. The
      volatile compositions of A. lepidophyllus and S. zenkeri oils supported their use
      as odorous spices. The significant inhibition activities detected make these oils
      worthy of further investigation as promising chemopreventive agents to be
      exploited in the African pharmaceutical market. 

PMID- 24443438
TI  - Evolution and classification of myosins, a paneukaryotic whole-genome approach.
AB  - Myosins are key components of the eukaryotic cytoskeleton, providing motility for
      a broad diversity of cargoes. Therefore, understanding the origin and
      evolutionary history of myosin classes is crucial to address the evolution of
      eukaryote cell biology. Here, we revise the classification of myosins using an
      updated taxon sampling that includes newly or recently sequenced genomes and
      transcriptomes from key taxa. We performed a survey of eukaryotic genomes and
      phylogenetic analyses of the myosin gene family, reconstructing the myosin
      toolkit at different key nodes in the eukaryotic tree of life. We also identified
      the phylogenetic distribution of myosin diversity in terms of number of genes,
      associated protein domains and number of classes in each taxa. Our analyses show
      that new classes (i.e., paralogs) and domain architectures were continuously
      generated throughout eukaryote evolution, with a significant expansion of myosin
      abundance and domain architectural diversity at the stem of Holozoa, predating
      the origin of animal multicellularity. Indeed, single-celled holozoans have the
      most complex myosin complement among eukaryotes, with paralogs of most myosins
      previously considered animal specific. We recover a dynamic evolutionary history,
      with several lineage-specific expansions (e.g., the myosin III-like gene family
      diversification in choanoflagellates), convergence in protein domain
      architectures (e.g., fungal and animal chitin synthase myosins), and important
      secondary losses. Overall, our evolutionary scheme demonstrates that the
      ancestral eukaryote likely had a complex myosin repertoire that included six
      genes with different protein domain architectures. Finally, we provide an
      integrative and robust classification, useful for future genomic and functional
      studies on this crucial eukaryotic gene family. 

PMID- 24443439
TI  - Evolution of a cellular immune response in Drosophila: a phenotypic and genomic
      comparative analysis.
AB  - Understanding the genomic basis of evolutionary adaptation requires insight into
      the molecular basis underlying phenotypic variation. However, even changes in
      molecular pathways associated with extreme variation, gains and losses of
      specific phenotypes, remain largely uncharacterized. Here, we investigate the
      large interspecific differences in the ability to survive infection by
      parasitoids across 11 Drosophila species and identify genomic changes associated
      with gains and losses of parasitoid resistance. We show that a cellular immune
      defense, encapsulation, and the production of a specialized blood cell,
      lamellocytes, are restricted to a sublineage of Drosophila, but that
      encapsulation is absent in one species of this sublineage, Drosophila sechellia.
      Our comparative analyses of hemopoiesis pathway genes and of genes differentially
      expressed during the encapsulation response revealed that hemopoiesis-associated
      genes are highly conserved and present in all species independently of their
      resistance. In contrast, 11 genes that are differentially expressed during the
      response to parasitoids are novel genes, specific to the Drosophila sublineage
      capable of lamellocyte-mediated encapsulation. These novel genes, which are
      predominantly expressed in hemocytes, arose via duplications, whereby five of
      them also showed signatures of positive selection, as expected if they were
      recruited for new functions. Three of these novel genes further showed large
      scale and presumably loss-of-function sequence changes in D. sechellia,
      consistent with the loss of resistance in this species. In combination, these
      convergent lines of evidence suggest that co-option of duplicated genes in
      existing pathways and subsequent neofunctionalization are likely to have
      contributed to the evolution of the lamellocyte-mediated encapsulation in
      Drosophila. 

PMID- 24443440
TI  - The effect of desmopressin on platelet function: a selective enhancement of
      procoagulant COAT platelets in patients with primary platelet function defects.
AB  - 1-deamino-8-d-arginine vasopressin (desmopressin [DDAVP]) is clinically
      efficacious in patients with mild platelet function disorders but it is not known
      which mechanisms mediate this effect. Our aim was to evaluate the impact of in
      vivo DDAVP administration in these patients. We assessed von Willebrand factor
      (VWF), factor VIII, platelet activation and aggregation, platelet-dependent
      thrombin generation, and platelet intracellular Na(+)/Ca(2+) fluxes, before and 2
      and 4 hours after DDAVP (0.3 ug/kg). We found (1) no significant changes for P
      selectin expression, PAC-1 binding, delta-granule content and secretion, and
      platelet-aggregation; (2) significant decreases of secretion of alpha-granules
      and GPIIb-IIIa activation induced by adenosine 5'-diphosphate, convulxin, and
      thrombin; (3) significant increases of procoagulant platelets induced by
      convulxin/thrombin and platelet-dependent thrombin generation; and (4)
      significant increases of intracellular Na(+)/Ca(2+) concentrations. We show that
      in vivo DDAVP selectively and markedly enhances the ability to form procoagulant
      platelets and increases platelet-dependent thrombin generation by enhancing
      Na(+)/Ca(2+) mobilization. This report indicates that the beneficial hemostatic
      effect of DDAVP is not limited to an increase in large VWF multimers. An
      enhancement of platelet procoagulant activity appears to be an additional and (at
      least in platelet disorders) -possibly clinically relevant mechanism of DDAVP's
      action. 

PMID- 24443441
TI  - Mutations in Kruppel-like factor 1 cause transfusion-dependent hemolytic anemia
      and persistence of embryonic globin gene expression.
AB  - In this study, we report on 8 compound heterozygotes for mutations in the key
      erythroid transcription factor Kruppel-like factor 1 in patients who presented
      with severe, transfusion-dependent hemolytic anemia. In most cases, the red cells
      were hypochromic and microcytic, consistent with abnormalities in hemoglobin
      synthesis. In addition, in many cases, the red cells resembled those seen in
      patients with membrane defects or enzymopathies, known as chronic nonspherocytic
      hemolytic anemia (CNSHA). Analysis of RNA and protein in primary erythroid cells
      from these individuals provided evidence of abnormal globin synthesis, with
      persistent expression of fetal hemoglobin and, most remarkably, expression of
      large quantities of embryonic globins in postnatal life. The red cell membranes
      were abnormal, most notably expressing reduced amounts of CD44 and, consequently,
      manifesting the rare In(Lu) blood group. Finally, all tested patients showed
      abnormally low levels of the red cell enzyme pyruvate kinase, a known cause of
      CNSHA. These patients define a new type of severe, transfusion-dependent CNSHA
      caused by mutations in a trans-acting factor (Kruppel-like factor 1) and reveal
      an important pathway regulating embryonic globin gene expression in adult humans.

PMID- 24443442
TI  - Impact of ruxolitinib on the natural history of primary myelofibrosis: a
      comparison of the DIPSS and the COMFORT-2 cohorts.
AB  - The international prognostic scoring system (IPSS) provides reliable risk
      assessment in patients with primary myelofibrosis (PMF). Recent clinical trials
      in PMF patients with intermediate-2 or high IPSS risk have shown a survival
      advantage of ruxolitinib over placebo (COMFORT-1) or best available therapy
      (COMFORT-2). Because crossover was allowed in these studies, we analyzed the
      cohort of ruxolitinib-naive patients used for developing the dynamic IPSS
      (DIPSS). By adopting ad hoc statistical analyses, we compared survival from
      diagnosis of 100 PMF patients receiving ruxolitinib within COMFORT-2 with that of
      350 patients of the DIPSS study. Subjects were properly matched, and both left
      truncation and right-censoring were accounted in order to compare higher IPSS
      risks exclusively. Patients receiving ruxolitinib had longer survival (5 years,
      95% confidence interval [CI]: 2.9-7.8 vs 3.5 years, 95% CI: 3.0-3.9) with a
      hazard ratio of 0.61 (95% CI: 0.41-0.91; P = .0148). This observation suggests
      that ruxolitinib may modify the natural history of PMF. 

PMID- 24443443
TI  - A distorted circadian clock causes early flowering and temperature-dependent
      variation in spike development in the Eps-3Am mutant of einkorn wheat.
AB  - Viable circadian clocks help organisms to synchronize their development with
      daily and seasonal changes, thereby providing both evolutionary fitness and
      advantage from an agricultural perspective. A high-resolution mapping approach
      combined with mutant analysis revealed a cereal ortholog of Arabidopsis thaliana
      LUX ARRHYTHMO/PHYTOCLOCK 1 (LUX/PCL1) as a promising candidate for the earliness
      per se 3 (Eps-3A(m)) locus in einkorn wheat (Triticum monococcum L.). Using
      delayed fluorescence measurements it was shown that Eps-3A(m) containing einkorn
      wheat accession KT3-5 had a distorted circadian clock. The hypothesis was
      subsequently confirmed by performing a time course study on central and output
      circadian clock genes, which showed arrhythmic transcript patterns in KT3-5 under
      constant ambient conditions, i.e., constant light and temperature. It was also
      demonstrated that variation in spikelet number between wild-type and mutants is
      sensitive to temperature, becoming negligible at 25 degrees . These observations
      lead us to propose that the distorted clock is causative for both early flowering
      and variation in spike size and spikelet number, and that having a dysfunctional
      LUX could have neutral, or even positive, effects in warmer climates. To test the
      latter hypothesis we ascertained sequence variation of LUX in a range of wheat
      germplasm. We observed a higher variation in the LUX sequence among accessions
      coming from the warmer climate and a unique in-frame mutation in early-flowering
      Chinese T. turgidum cultivar 'Tsing Hua no. 559.' Our results emphasize the
      importance of the circadian clock in temperate cereals as a promising target for
      adaptation to new environments. 

PMID- 24443444
TI  - Genomic signature of adaptation to climate in Medicago truncatula.
AB  - Local adaptation and adaptive clines are pervasive in natural plant populations,
      yet the effects of these types of adaptation on genomic diversity are not well
      understood. With a data set of 202 accessions of Medicago truncatula genotyped at
      almost 2 million single nucleotide polymorphisms, we used mixed linear models to
      identify candidate loci responsible for adaptation to three climatic gradients
      annual mean temperature (AMT), precipitation in the wettest month (PWM), and
      isothermality (ITH)-representing the major axes of climate variation across the
      species' range. Loci with the strongest association to these climate gradients
      tagged genome regions with high sequence similarity to genes with functional
      roles in thermal tolerance, drought tolerance, or resistance to herbivores of
      pathogens. Genotypes at these candidate loci also predicted the performance of an
      independent sample of plant accessions grown in climate-controlled conditions.
      Compared to a genome-wide sample of randomly drawn reference SNPs, candidates for
      two climate gradients, AMT and PWM, were significantly enriched for genic
      regions, and genome segments flanking genic AMT and PWM candidates harbored less
      nucleotide diversity, elevated differentiation between haplotypes carrying
      alternate alleles, and an overrepresentation of the most common haplotypes. These
      patterns of diversity are consistent with a history of soft selective sweeps
      acting on loci underlying adaptation to climate, but not with a history of long
      term balancing selection. 

PMID- 24443446
TI  - Only half of patients referred for talking therapies enter treatment.

PMID- 24443445
TI  - Characterization of genetic diversity in the nematode Pristionchus pacificus from
      population-scale resequencing data.
AB  - The hermaphroditic nematode Pristionchus pacificus is an established model system
      for comparative studies with Caenorhabditis elegans in developmental biology,
      ecology, and population genetics. In this study, we present whole-genome
      sequencing data of 104 P. pacificus strains and the draft assembly of the
      obligate outcrossing sister species P. exspectatus. We characterize genetic
      diversity within P. pacificus and investigate the population genetic processes
      shaping this diversity. P. pacificus is 10 times more diverse than C. elegans and
      exhibits substantial population structure that allows us to probe its evolution
      on multiple timescales. Consistent with reduced effective recombination in this
      self-fertilizing species, we find haplotype blocks that span several megabases.
      Using the P. exspectatus genome as an outgroup, we polarized variation in P.
      pacificus and found a site frequency spectrum (SFS) that decays more rapidly than
      expected in neutral models. The SFS at putatively neutral sites is U shaped,
      which is a characteristic feature of pervasive linked selection. Based on the
      additional findings (i) that the majority of nonsynonymous variation is
      eliminated over timescales on the order of the separation between clades, (ii)
      that diversity is reduced in gene-rich regions, and (iii) that highly
      differentiated clades show very similar patterns of diversity, we conclude that
      purifying selection on many mutations with weak effects is a major force shaping
      genetic diversity in P. pacificus. 

PMID- 24443448
TI  - Individualized current-shaping reduces DBS-induced dysarthria in patients with
      essential tremor.
AB  - OBJECTIVE: To investigate in patients with essential tremor (ET) treated with
      thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced
      dysarthria (SID) can be diminished by individualized current-shaping with
      interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS).
      METHODS: Of 26 patients screened, 10 reported SID and were invited for testing.
      TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and
      action tremor. SID was assessed by phonetic and logopedic means. Additionally,
      patients rated their dysarthria on a visual analog scale. RESULTS: In 6 of the 10
      patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was
      successfully reduced. When comparing individualized cs-ILS with a non-current
      shaped interleaving stimulation (ILS) in these patients, there was no difference
      in TS while 4 of the 6 patients showed subjective improvement of speech during cs
      ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a
      reduction of voicing during the production of voiceless stop consonants and also
      a trend toward an improvement in oral diadochokinetic rate, reflecting less
      dysarthria. Logopedic rating showed a trend toward deterioration in the
      diadochokinesis task when comparing ON with OFF but no difference between ILS and
      cs-ILS. CONCLUSION: This is a proof-of-principle evaluation of current-shaping in
      patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data
      suggest a benefit on SID from individual shaping of current spread while TS is
      preserved. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that
      in patients with ET treated with DBS with SID, individualized cs-ILS reduces
      dysarthria while maintaining tremor control.

PMID- 24443449
TI  - Clinical and radiologic features of encephalopathy during 2011 E coli O111
      outbreak in Japan.
AB  - OBJECTIVE: To elucidate the clinical and radiologic features and analyze factors
      associated with neurologic outcomes of encephalopathy secondary to Shiga toxin
      producing Escherichia coli (STEC) O111. METHODS: We reviewed medical records and
      neuroimaging in 22 patients with neurologic symptoms among 86 with STEC O111
      infection. RESULTS: Twenty-one (6 males and 15 females, 10 children and 11
      adults) of the 22 patients were diagnosed with encephalopathy. All patients with
      encephalopathy also presented with hemolytic-uremic syndrome. Five patients died,
      from day 1 to 6 months (days 1-5 in 4 patients), due to progressive
      encephalopathy with severe cerebral edema observed in neuroimaging (4 patients).
      Fifteen of the 16 surviving patients clinically recovered completely. Statistical
      analysis revealed differences between patients with poor (n = 6) and good (n =
      15) outcomes in the interval from hemolytic-uremic syndrome presentation to
      encephalopathy, creatinine levels, and the methylprednisolone administration
      ratio. CONCLUSION: We note a high incidence of encephalopathy in the Toyama STEC
      O111 outbreak. All fatal cases resulted from progressive encephalopathy.
      Methylprednisolone pulse therapy represents a possible therapeutic choice.
      CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that
      methylprednisolone pulse therapy increases the probability of a good outcome for
      patients with encephalopathy associated with STEC O111.

PMID- 24443450
TI  - Seizures as first symptom of anti-NMDA receptor encephalitis are more common in
      men.

PMID- 24443451
TI  - Acid-sensing cation channels: structure, function, and pathophysiologic
      implications.

PMID- 24443452
TI  - Clinical specificities of adult male patients with NMDA receptor antibodies
      encephalitis.
AB  - OBJECTIVE: The aim of this study was to describe the clinical features and
      specificities of adult male patients with NMDA receptor antibodies (NMDAr-Abs)
      encephalitis. METHODS: Observational study of 13 adult male patients who were
      diagnosed with NMDAr-Abs encephalitis at the French Paraneoplastic Neurological
      Syndrome Reference Center. RESULTS: Adult male patients frequently presented
      initially with a seizure (8/13, 61.5%). Seizures were partial in 5/8 patients and
      were followed only a few days later (median 12 days; range 2-17 days) by
      psychiatric or cognitive symptoms. Conversely, adult female patients rarely
      presented with a seizure initially (8/58, 14%, p < 0.001), and most of their
      seizures were generalized and were rapidly followed (median 2 days; range 1-7
      days) by behavioral and psychiatric features. Additionally, in male patients the
      disease was rarely associated with a tumor (1/13 or 8%, a perineal schwannoma);
      in contrast, 41% of female patients had an associated tumor (95% of which were
      ovarian teratomas; p = 0.02 male vs female association with tumor). The
      incidences of abnormalities in ancillary tests, treatment modalities, clinical
      evolution, and outcome were equal for both subgroups. CONCLUSION: Adult male
      patients who have partial seizures, normal MRI results, and no clear etiology
      should be tested for NMDAr-Abs to avoid any delays in treatment initiation. Adult
      female patients who had a seizure as the first symptom are infrequent when NMDAr
      Abs encephalitis is diagnosed; additionally, their clinical pattern is different
      from male patients, with more generalized seizures and rapid development of
      behavioral and psychiatric symptoms. The differences in hormonal influence could
      contribute to this difference in clinical pattern.

PMID- 24443453
TI  - Corticobasal syndrome associated with antiphospholipid syndrome without cerebral
      infarction.

PMID- 24443455
TI  - Saving lives by treating epilepsy in developing countries.

PMID- 24443454
TI  - Premature mortality in active convulsive epilepsy in rural Kenya: causes and
      associated factors.
AB  - OBJECTIVE: We estimated premature mortality and identified causes of death and
      associated factors in people with active convulsive epilepsy (ACE) in rural
      Kenya. METHODS: In this prospective population-based study, people with ACE were
      identified in a cross-sectional survey and followed up regularly for 3 years,
      during which information on deaths and associated factors was collected. We used
      a validated verbal autopsy tool to establish putative causes of death. Age
      specific rate ratios and standardized mortality ratios were estimated. Poisson
      regression was used to identify mortality risk factors. RESULTS: There were 61
      deaths among 754 people with ACE, yielding a rate of 33.3/1,000 persons/year.
      Overall standardized mortality ratio was 6.5. Mortality was higher across all ACE
      age groups. Nonadherence to antiepileptic drugs (adjusted rate ratio [aRR] 3.37),
      cognitive impairment (aRR 4.55), and age (50+ years) (rate ratio 4.56) were risk
      factors for premature mortality. Most deaths (56%) were directly related to
      epilepsy, with prolonged seizures/possible status epilepticus (38%) most
      frequently associated with death; some of these may have been due to sudden
      unexpected death in epilepsy (SUDEP). Possible SUDEP was the likely cause in
      another 7%. CONCLUSION: Mortality in people with ACE was more than 6-fold greater
      than expected. This may be reduced by improving treatment adherence and prompt
      management of prolonged seizures and supporting those with cognitive impairment.

PMID- 24443456
TI  - Safeguarding global health: FAO calls for a 'paradigm shift'.

PMID- 24443457
TI  - EFSA recommends a toolbox of indicators for monitoring welfare at slaughter.

PMID- 24443458
TI  - Government 'will not shy away' from difficult decisions on bovine TB.

PMID- 24443459
TI  - Centralise surveillance diagnostics in Scotland, says Moredun CEO.

PMID- 24443461
TI  - Recognising - and promoting - excellent care of working equids.

PMID- 24443463
TI  - UK charity vets get a US perspective on shelter medicine.
AB  - Shelter medicine is very much a recognised discipline within veterinary medicine
      in the USA, with increasing numbers of veterinary students receiving specific
      teaching in the field. Delegates at the second meeting of the Association of
      Charity Vets, which was held at Nottingham veterinary school in November last
      year, learned more about the US approach to this evolving field. 

PMID- 24443464
TI  - Focus on emergency medicine.
AB  - Manuela Herrera reports from the 10th Emergency and Critical Care UK annual
      congress, hosted by Vets Now, which was held in Harrogate last November. More
      than 500 small animal veterinary surgeons, veterinary nurses, practice managers
      and receptionists attended the meeting to learn more about all aspects of
      emergency care. 

PMID- 24443465
TI  - Applying games technology to veterinary teaching.
AB  - Veterinarian Marton Balogh has been interested in computers, gaming and
      programming since he was eight years old. Here, he explains how he is using
      software that is more often associated with the creation of 3D computer games to
      develop an immersive, virtual consultation room, complete with patient, to help
      train veterinary students in clinical examination techniques. 

PMID- 24443466
TI  - Border disease virus: time to take more notice?

PMID- 24443467
TI  - The RCVS codes of conduct: what's in a word?
AB  - In 2012, the RCVS introduced a new Code of Professional Conduct for Veterinary
      Surgeons, replacing the Guide to Professional Conduct which had existed until
      then. Is a common Code relevant for the veterinarian's many roles? There's more
      to think about here than just the change of name, write Steven McCulloch, Michael
      Reiss, Peter Jinman and Christopher Wathes. 

PMID- 24443468
TI  - Keeping exotic pets.

PMID- 24443469
TI  - Cranial osteomyelitis due to E coli infection in commercial layers.

PMID- 24443470
TI  - Controlling Angiostrongylus vasorum infection in dogs.

PMID- 24443472
TI  - Cimodo virus belongs to a novel lineage of reoviruses isolated from African
      mosquitoes.
AB  - A novel reovirus, designated Cimodo virus (CMDV), was isolated from mosquitoes
      collected in a rainforest region in Cote d'Ivoire. The entire genome comprised 24
      835 bp divided into 12 segments ranging from 585 to 4080 bp. The icosahedral non
      enveloped virions were 80 nm in diameter. Eight major viral proteins of about
      150, 135, 120, 80, 66, 59, 42 and 30 kDa were identified and seven proteins were
      mapped to the corresponding genome segments by liquid chromatography mass
      spectrometry. Predicted protein genes diverged by >77 % encoded amino acids from
      their closest reovirus relatives. The deep phylogenetic branching suggests that
      CMDV defines an as-yet-unidentified genus within the subfamily Spinareovirinae. 

PMID- 24443471
TI  - Enhancer-targeted genome editing selectively blocks innate resistance to
      oncokinase inhibition.
AB  - Thousands of putative enhancers are characterized in the human genome, yet few
      have been shown to have a functional role in cancer progression. Inhibiting
      oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is a mainstay of current cancer
      therapy but is hindered by innate drug resistance mediated by up-regulation of
      the HGF receptor, MET. The mechanisms mediating such genomic responses to
      targeted therapy are unknown. Here, we identify lineage-specific enhancers at the
      MET locus for multiple common tumor types, including a melanoma lineage-specific
      enhancer 63 kb downstream from the MET TSS. This enhancer displays inducible
      chromatin looping with the MET promoter to up-regulate MET expression upon BRAF
      inhibition. Epigenomic analysis demonstrated that the melanocyte-specific
      transcription factor, MITF, mediates this enhancer function. Targeted genomic
      deletion (<7 bp) of the MITF motif within the MET enhancer suppressed inducible
      chromatin looping and innate drug resistance, while maintaining MITF-dependent,
      inhibitor-induced melanoma cell differentiation. Epigenomic analysis can thus
      guide functional disruption of regulatory DNA to decouple pro- and anti-oncogenic
      functions of a dominant transcription factor and block innate resistance to
      oncokinase therapy. 

PMID- 24443473
TI  - The ORF4b-encoded accessory proteins of Middle East respiratory syndrome
      coronavirus and two related bat coronaviruses localize to the nucleus and inhibit
      innate immune signalling.
AB  - The recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV), a
      betacoronavirus, is associated with severe pneumonia and renal failure. The
      environmental origin of MERS-CoV is as yet unknown; however, its genome sequence
      is closely related to those of two bat coronaviruses, named BtCoV-HKU4 and BtCoV
      HKU5, which were derived from Chinese bat samples. A hallmark of highly
      pathogenic respiratory viruses is their ability to evade the innate immune
      response of the host. CoV accessory proteins, for example those from severe acute
      respiratory syndrome CoV (SARS-CoV), have been shown to block innate antiviral
      signalling pathways. MERS-CoV, similar to SARS-CoV, has been shown to inhibit
      type I IFN induction in a variety of cell types in vitro. We therefore
      hypothesized that MERS-CoV and the phylogenetically related BtCoV-HKU4 and BtCoV
      HKU5 may encode proteins with similar capabilities. In this study, we have
      demonstrated that the ORF4b-encoded accessory protein (p4b) of MERS-CoV, BtCoV
      HKU4 and BtCoV-HKU5 may indeed facilitate innate immune evasion by inhibiting the
      type I IFN and NF-kappaB signalling pathways. We also analysed the subcellular
      localization of p4b from MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 and demonstrated
      that all are localized to the nucleus. 

PMID- 24443474
TI  - Proteomic analyses of baculovirus Anticarsia gemmatalis multiple
      nucleopolyhedrovirus budded and occluded virus.
AB  - Baculoviruses infect insects, producing two distinct phenotypes during the viral
      life cycle: the budded virus (BV) and the occlusion-derived virus (ODV) for intra
      and inter-host spread, respectively. Since the 1980s, several countries have
      been using Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) as a
      biological control agent against the velvet bean caterpillar, A. gemmatalis. The
      genome of AgMNPV isolate 2D (AgMNPV-2D) carries at least 152 potential genes,
      with 24 that possibly code for structural proteins. Proteomic studies have been
      carried out on a few baculoviruses, with six ODV and two BV proteomes completed
      so far. Moreover, there are limited data on virion proteins carried by AgMNPV-2D.
      Therefore, structural proteins of AgMNPV-2D were analysed by MALDI- quadrupole
      TOF and liquid chromatography MS/MS. A total of 44 proteins were associated with
      the ODV and 33 with the BV of AgMNPV-2D. Although 38 structural proteins were
      already known, we found six new proteins in the ODV and seven new proteins
      carried by the AgMNPV-2D BV. Eleven cellular proteins that were found on several
      other enveloped viruses were also identified, which are possibly carried with the
      virion. These findings may provide novel insights into baculovirus biology and
      their host interaction. Moreover, our data may be helpful in subsequent applied
      studies aiming to improve AgMNPV use as a biopesticide and a biotechnology tool
      for gene expression or delivery. 

PMID- 24443475
TI  - Introductory paragraph--volume 28, issue 2.

PMID- 24443476
TI  - High-frequency chest wall oscillation in infective exacerbation of COPD: is
      airway secretion clearance the cornerstone?

PMID- 24443477
TI  - Bad medicine: the rise of duloxetine.

PMID- 24443478
TI  - Assessment of US pathway for approving medical devices for rare conditions.

PMID- 24443479
TI  - Biosimilars: what's in a name?

PMID- 24443480
TI  - A shared wave is a clinical test of health--and humanity.

PMID- 24443481
TI  - Impaired left ventricular function and myocardial blood flow reserve in patients
      with long-term type 1 diabetes and no significant coronary artery disease:
      associations with protein glycation.
AB  - Our aims were to study left ventricular (LV) function and myocardial blood flow
      reserve (MBFR) in long-term type 1 diabetes and associations with advanced
      glycation end products (AGEs). A total of 20 type 1 diabetes patients from the
      Oslo Study without significant stenosis on coronary angiography were compared
      with 26 controls. LV systolic and diastolic functions were assessed by two
      dimensional strain and the ratio between pulsed Doppler transmitral early (E)
      velocity and tissue Doppler velocity (E'), respectively. MBFR was evaluated by
      contrast echocardiography. The AGE methylglyoxal-derived hydroimidazolone was
      analysed in serum. Glyoxal hydroimidazolone in skin collagen was determined by
      liquid chromatography-mass spectrometry. Strain was significantly reduced (-19.5%
      +/- 1.9% vs -21.4% +/- 3.5%, p < 0.05), and E/E' increased in the diabetes
      patients compared to controls, 7.3 +/- 2 versus 6.0 +/- 1.5, p < 0.05.
      Significant lower MBFR was present in the diabetes patients, 3.4 (2.1, 5.3)
      versus 5.9 (3.9, 9.6), p < 0.01. Both AGEs correlated significantly with E/E'.
      The impaired LV function with correlation to AGEs in concert with reduced MBFR in
      diabetics without coronary artery disease may indicate possible mechanisms for
      diabetic cardiomyopathy. 

PMID- 24443486
TI  - England's mental and community health services face deeper cuts than hospitals.

PMID- 24443487
TI  - Private companies won 70% of contracts awarded by England's commissioning groups
      in opening months.

PMID- 24443490
TI  - Prevention of spinal cord injury.

PMID- 24443491
TI  - Prospective study of hammertoe correction with an intramedullary implant.
AB  - BACKGROUND: Operative correction of a hammertoe deformity is often accomplished
      by excision of the articular surface of the proximal interphalangeal joint (PIP)
      and fixation across the joint. This study aimed to prospectively evaluate
      clinical and radiographic outcomes of hammertoe operative correction utilizing an
      internal implant and assess its ability to maintain postoperative alignment.
      METHODS: Twenty-nine patients (53 toes) with a painful rigid hammertoe deformity
      were prospectively enrolled and operatively treated with resection arthroplasty
      of the PIP joint and fixation with an implant. Five patients were lost to follow
      up, and 24 patients (42 toes) returned at an average of 12 months for final
      clinical and radiographic evaluation. All patients were evaluated pre- and
      postoperatively by AOFAS and Visual Analog Pain Scale (VAS) scores. On physical
      exam, the location and magnitude of the deformity, callosities, and digit
      circumference were recorded. Radiological parameters evaluated were digital
      alignment, successful union, implant position, and bone reaction. RESULTS: All
      patients reported satisfaction at final follow-up, with an average improvement of
      AOFAS score from 52 (range, 24-87 points) to 71 (range, 42-95 points) points. The
      mean VAS pain score improved from 5 points (range, 2 to 10) preoperatively to 1
      point (range, 0 to 5) postoperatively. Of patients, 87% reported an ability to
      return to their preoperative activities without limitations. Regarding digital
      alignment, there were no recurrent deformities or transverse plane deformities; 1
      toe presented with a minor digital rotational deformity at final follow-up.
      Postoperative radiographs indicated 100% of proximal interphalangeal (PIP) joints
      with good alignment, and 81% demonstrated bony union. CONCLUSION: Our results
      suggest that utilization of an internal implant for hammertoe correction was safe
      and provided acceptable alignment, pain reduction, and improved function at final
      follow-up. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24443492
TI  - Reply to Corrao et al.

PMID- 24443493
TI  - Healthcare-associated pneumonia and multidrug-resistant bacteria: do we have a
      convincing answer?

PMID- 24443494
TI  - CRISPR/Cas9-mediated targeted mutagenesis in the liverwort Marchantia polymorpha
      L.
AB  - Targeted genome modification technologies are key tools for functional genomics.
      The clustered regularly interspaced short palindromic repeats (CRISPR)-associated
      endonuclease Cas9 system (CRISPR/Cas9) is an emerging technology for targeted
      genome modification. The CRISPR/Cas9 system consists of a short guide RNA (gRNA),
      which specifies the target genome sequence, and the Cas9 protein, which has
      endonuclease activity. The CRISPR/Cas9 system has been applied to model animals
      and flowering plants, including rice, sorghum, wheat, tobacco and Arabidopsis.
      Here, we report the application of CRISPR/Cas9 to targeted mutagenesis in the
      liverwort Marchantia polymorpha L., which has emerged as a model species for
      studying land plant evolution. The U6 promoter of M. polymorpha was identified
      and cloned to express the gRNA. The target sequence of the gRNA was designed to
      disrupt the gene encoding auxin response factor 1 (ARF1) in M. polymorpha. Using
      Agrobacterium-mediated transformation, we isolated stable mutants in the
      gametophyte generation of M. polymorpha. CRISPR/Cas9-based site-directed
      mutagenesis in vivo was achieved using either the Cauliflower mosaic virus 35S or
      M. polymorpha EF1alpha promoter to express Cas9. Isolated mutant individuals
      showing an auxin-resistant phenotype were not chimeric. Moreover, stable mutants
      were produced by asexual reproduction of T1 plants. Multiple arf1 alleles were
      easily established using CRIPSR/Cas9-based targeted mutagenesis. Our results
      provide a rapid and simple approach for molecular genetics in M. polymorpha, and
      raise the possibility that CRISPR/Cas9 may be applied to a wide variety of plant
      species. 

PMID- 24443495
TI  - VAN4 encodes a putative TRS120 that is required for normal cell growth and vein
      development in Arabidopsis.
AB  - Leaf venation develops complex patterns in angiosperms, but the mechanism
      underlying this process is largely unknown. To elucidate the molecular mechanisms
      governing vein pattern formation, we previously isolated vascular network
      defective (van) mutants that displayed venation discontinuities. Here, we report
      the phenotypic analysis of van4 mutants, and we identify and characterize the
      VAN4 gene. Detailed phenotypic analysis shows that van4 mutants are defective in
      procambium cell differentiation and subsequent vascular cell differentiation.
      Reduced shoot and root cell growth is observed in van4 mutants, suggesting that
      VAN4 function is important for cell growth and the establishment of venation
      continuity. Consistent with these phenotypes, the VAN4 gene is strongly expressed
      in vascular and meristematic cells. VAN4 encodes a putative TRS120, which is a
      known guanine nucleotide exchange factor (GEF) for Rab GTPase involved in
      regulating vesicle transport, and a known tethering factor that determines the
      specificity of membrane fusion. VAN4 protein localizes at the trans-Golgi
      network/early endosome (TGN/EE). Aberrant recycling of the auxin efflux carrier
      PIN proteins is observed in van4 mutants. These results suggest that VAN4
      mediated exocytosis at the TGN plays important roles in plant vascular
      development and cell growth in shoot and root. Our identification of VAN4 as a
      putative TRS120 shows that Rab GTPases are crucial (in addition to ARF GTPases)
      for continuous vascular development, and provides further evidence for the
      importance of vesicle transport in leaf vascular formation. 

PMID- 24443496
TI  - Dynamic behavior of the trans-golgi network in root tissues of Arabidopsis
      revealed by super-resolution live imaging.
AB  - The trans-Golgi network (TGN) is an important organelle for protein transport at
      the post-Golgi network, which functions as a sorting station that directs cargo
      proteins to a variety of destinations including post-Golgi compartments and the
      extracellular space. However, the functions and dynamics of the TGN in plant
      cells have not been well understood yet. To elucidate the dynamics of the plant
      TGN, we established transgenic plants expressing green fluorescent protein (GFP)
      SYP43, the ortholog of Tlg2/syntaxin16, which is localized to the TGN in yeast
      and mammalian cells, under the control of the native promoter as a TGN marker.
      Observation by confocal laser scanning microscopy and super-resolution confocal
      live imaging microscopy revealed two types of TGN in Arabidopsis root: the GA
      TGNs (Golgi-associated TGNs), located on the trans-side of the Golgi apparatus,
      and the GI-TGNs (Golgi-released independent TGNs), located away from the Golgi
      apparatus and behaving independently. The GI-TGNs is derived from a population of
      GA-TGNs by segregation, although the core of the GA-TGN remains even after the
      generation of the GI-TGN. We further found that the abundance of the GI-TGNs
      differs between observed tissues. Our results indicate that the dynamic features
      of the TGN in plant cells differ from those of animal and yeast cells. 

PMID- 24443497
TI  - Do the rich always become richer? Characterizing the leaf physiological response
      of the high-yielding rice cultivar Takanari to free-air CO2 enrichment.
AB  - The development of crops which are well suited to growth under future
      environmental conditions such as higher atmospheric CO2 concentrations ([CO2]) is
      essential to meeting the challenge of ensuring food security in the face of the
      growing human population and changing climate. A high-yielding indica rice
      variety (Oryza sativa L. cv. Takanari) has been recently identified as a
      potential candidate for such breeding, due to its high productivity in present
      [CO2]. To test if it could further increase its productivity under elevated [CO2]
      (eCO2), Takanari was grown in the paddy field under season-long free-air CO2
      enrichment (FACE, approximately 200 umol mol(-1) above ambient [CO2]) and its
      leaf physiology was compared with the representative japonica variety
      'Koshihikari'. Takanari showed consistently higher midday photosynthesis and
      stomatal conductance than Koshihikari under both ambient and FACE growth
      conditions over 2 years. Maximum ribulose-1,5-bisphosphate carboxylation and
      electron transport rates were higher for Takanari at the mid-grain filling stage
      in both years. Mesophyll conductance was higher in Takanari than in Koshihikari
      at the late grain-filling stage. In contrast to Koshihikari, Takanari grown under
      FACE conditions showed no decrease in total leaf nitrogen on an area basis
      relative to ambient-grown plants. Chl content was higher in Takanari than in
      Koshihikari at the same leaf nitrogen level. These results indicate that Takanari
      maintains its superiority over Koshihikari in regards to its leaf-level
      productivity when grown in elevated [CO2] and it may be a valuable resource for
      rice breeding programs which seek to increase crop productivity under current and
      future [CO2]. 

PMID- 24443498
TI  - Targeted metabolomics of Physaria fendleri, an industrial crop producing hydroxy
      fatty acids.
AB  - Physaria fendleri (syn. Lesquerella) is a Brassicaceae producing lesquerolic
      acid, a highly valued hydroxy fatty acid that could be used for several
      industrial applications, such as cosmetics, lubricating greases, paints, plastics
      and biofuels. Free of toxins, Physaria oil is an attractive alternative to
      imported castor (Ricinus communis) oil, and is hence on the verge of
      commercialization. Gas chromatography-mass spectrometry analysis of fatty acid
      methyl esters revealed that lesquerolic acid was synthesized and accumulated in
      the embryos, reaching 60% (w/w) of the total fatty acids. The sequential
      extraction and characterization of biomass compounds revealed that Physaria
      embryo metabolism switched from protein to fatty acid biosynthesis between 18 and
      24 days post-anthesis (DPA). In order to unravel the metabolic pathways involved
      in fatty acid synthesis, a targeted metabolomics study was conducted on Physaria
      embryos at different stages of development. For this purpose, two novel high
      throughput liquid chromatography-tandem mass spectrometry methods were developed
      and validated to quantify sugars, sugar alcohols and amino acids. Specificity was
      achieved using multiple reaction monitoring, and the limits of quantification
      were in the pmole-fmole range. The comparative metabolomic study underlined that:
      (i) the majority of the metabolites accumulate in Physaria embryos between 18 and
      27 DPA; (ii) the oxidative pentose phosphate pathway, glycolysis, the
      tricarboxilic acid cycle and the anaplerotic pathway drain a substantial amount
      of carbon; and (iii) ribulose-1,5-bisphosphate is present, which specifically
      indicates that the Calvin cycle is occurring. The importance and the relevance of
      these findings regarding fatty acid synthesis were discussed. 

PMID- 24443499
TI  - A role for PacMYBA in ABA-regulated anthocyanin biosynthesis in red-colored sweet
      cherry cv. Hong Deng (Prunus avium L.).
AB  - The MYB transcription factors and plant hormone ABA have been suggested to play a
      role in fruit anthocyanin biosynthesis, but supporting genetic evidence has been
      lacking in sweet cherry. The present study describes the first functional
      characterization of an R2R3-MYB transcription factor, PacMYBA, from red-colored
      sweet cherry cv. Hong Deng (Prunus avium L.). Transient promoter assays
      demonstrated that PacMYBA physically interacted with several anthocyanin-related
      basic helix-loop-helix (bHLH) transcription factors to activate the promoters of
      PacDFR, PacANS and PacUFGT, which are thought to be involved in anthocyanin
      biosynthesis. Furthermore, the immature seeds of transgenic Arabidopsis plants
      overexpressing PacMYBA exhibited ectopic pigmentation. Silencing of PacMYBA,
      using a Tobacco rattle virus (TRV)-induced gene silencing technique, resulted in
      sweet cherry fruit that lacked red pigment. ABA treatment significantly induced
      anthocyanin accumulation, while treatment with the ABA biosynthesis inhibitor
      nordihydroguaiaretic acid (NDGA) blocked anthocyanin production. PacMYBA
      expression peaked after 2 h of pre-incubation in ABA and was 15.2-fold higher
      than that of sweet cherries treated with NDGA. The colorless phenotype was also
      observed in the fruits silenced in PacNCED1, which encodes a key enzyme in the
      ABA biosynthesis pathway. The endogenous ABA content as well as the transcript
      levels of six structural genes and PacMYBA in PacNCED1-RNAi (RNA interference)
      fruit were significantly lower than in the TRV vector control fruit. These
      results suggest that PacMYBA plays an important role in ABA-regulated anthocyanin
      biosynthesis and ABA is a signal molecule that promotes red-colored sweet cherry
      fruit accumulating anthocyanin. 

PMID- 24443500
TI  - Representativeness.

PMID- 24443501
TI  - Commentary: Political epidemiology, Republican presidents and dog food.

PMID- 24443502
TI  - Contextualising eating problems in individual diet counselling.
AB  - Health professionals consider diet to be a vital component in managing weight,
      chronic diseases and the overall promotion of health. This article takes the
      position that the complexity and contextual nature of individual eating problems
      needs to be addressed in a more systematic and nuanced way than is usually the
      case in diet counselling, motivational interviewing and health coaching. We
      suggest the use of narrative practice as a critical and context-sensitive
      counselling approach to eating problems. Principles of externalisation and co
      researching are combined within a counselling framework that employs logistic,
      social and discursive eating problems as analytic categories. Using cases from a
      health clinic situated at the Metropolitan University College in Copenhagen, we
      show that even if the structural conditions associated with eating problems may
      not be solvable through individual counselling sessions, exploration of the
      complex structures of food and eating with the client can provide agency by
      helping them navigate within the context of the problem. We also exemplify why a
      reflexive and critical approach to the way health is perceived by clients should
      be an integrated part of diet counselling. 

PMID- 24443503
TI  - Impairment effects, disability and dry mouth: Exploring the public and private
      dimensions.
AB  - Existing accounts of dry mouth concentrate on the medical dimensions and almost
      completely neglect to consider its social dimensions. Simultaneously, debates on
      disability have highlighted an apparent split between the individual (medical)
      and social models of disability. The concept of 'impairment effects' aims to
      address this dichotomised approach. Impairment effects consider the everyday
      impact of people's impairments on their lives in conjunction with the disabling
      impacts encountered through their relations with society, and society's relations
      with them. This study indicates that identity and self became entangled with
      impairment effects and a form of disablism. The authors argue that impairment
      effects are, at times, a useful concept, but in some instances may actually
      overcomplicate things. By analysing the public and private dimensions of a
      chronic condition such as dry mouth, we have been enabled to explore the boundary
      between public and private lives. As a consequence, using public and private
      accounts may assist us to better locate the point where impairment ends and
      disability begins. 

PMID- 24443504
TI  - Target indices for clinical ablation in atrial fibrillation: insights from
      contact force, electrogram, and biophysical parameter analysis.
AB  - BACKGROUND: In animal studies of radiofrequency ablation, lesion sizes plateau as
      the maximum lesion size is reached for an ablation. Lesion parameters are not
      available in clinical ablations, but preclinical work suggests that these
      correlate with impedance drop and electrogram attenuation. Characterization of
      the relationships between catheter contact force, ablation duration, and these
      surrogate markers of lesion formation may allow us to define targets for
      effective ablation. METHODS AND RESULTS: Fifteen patients undergoing first-time
      radiofrequency ablation for nonparoxysmal atrial fibrillation were studied. All
      were in atrial fibrillation at the time of the procedure. Ablations were
      performed with an irrigated-tip contact force-sensing catheter in temperature
      controlled mode (temperature limited to 48 degrees C, power to 30 W). Included
      were 285 left atrial static ablations, 247 with additional impedance data. The
      ablation force time integral (FTI) correlated with the attenuation of the
      electrogram with ablation (Spearman rho, -0.14; P=0.02): the relationship
      plateauing from 500 g.s, a reduction in the electrogram amplitude of 20%. The FTI
      also correlated with the impedance drop during ablation (Spearman rho, 0.79;
      P<0.0005): the relationship was logarithmic, the reduction in the impedance with
      an increasing FTI also plateauing from 500 g.s, an impedance drop of 7.5%. The
      ablation duration affected the impedance drop at an FTI if the duration was <10
      s. Beyond this time point, the FTI achieved rather than the ablation duration or
      mean contact force applied determined the impedance drop. CONCLUSIONS: During
      nonparoxysmal atrial fibrillation ablation, an FTI of 500 g.s should be targeted
      with ablation duration of >=10 s. Clinical Trials Registration- URL:
      http://clinicaltrials.gov/. Unique Identifier: NCT01587404.

PMID- 24443505
TI  - Celebrating diversity in memory T cells.

PMID- 24443506
TI  - Pillars article: two subsets of memory T lymphocytes with distinct homing
      potentials and effector functions. Nature. 1999. 401: 708-712.

PMID- 24443507
TI  - Pillars article: preferential localization of effector memory cells in
      nonlymphoid tissue. Science. 2001. 291: 2413-2417.

PMID- 24443512
TI  - Model of bipolar electrogram fractionation and conduction block associated with
      activation wavefront direction at infarct border zone lateral isthmus boundaries.
AB  - BACKGROUND: Improved understanding of the mechanisms underlying infarct border
      zone electrogram fractionation may be helpful to identify arrhythmogenic regions
      in the postinfarction heart. We describe the generation of electrogram
      fractionation from changes in activation wavefront curvature in experimental
      canine infarction. METHODS AND RESULTS: A model was developed to estimate the
      extracellular signal shape that would be generated by wavefront propagation
      parallel to versus perpendicular to the lateral boundary (LB) of the reentrant
      ventricular tachycardia (VT) isthmus or diastolic pathway. LBs are defined as
      locations where functional block forms during VT, and elsewhere they have been
      shown to coincide with sharp thin-to-thick transitions in infarct border zone
      thickness. To test the model, bipolar electrograms were acquired from infarct
      border zone sites in 10 canine heart experiments 3 to 5 days after experimental
      infarction. Activation maps were constructed during sinus rhythm and during VT.
      The characteristics of model-generated versus actual electrograms were compared.
      Quantitatively expressed VT fractionation (7.6+/-1.2 deflections; 16.3+/-8.9-ms
      intervals) was similar to model-generated values with wavefront propagation
      perpendicular to the LB (9.4+/-2.4 deflections; 14.4+/-5.2-ms intervals).
      Fractionation during sinus rhythm (5.9+/-1.8 deflections; 9.2+/-4.4-ms intervals)
      was similar to model-generated fractionation with wavefront propagation parallel
      to the LB (6.7+/-3.1 deflections; 7.1+/-3.8-ms intervals). VT and sinus rhythm
      fractionation sites were adjacent to LBs ~80% of the time. CONCLUSIONS: The
      results suggest that in a subacute canine infarct model, the LBs are a source of
      activation wavefront discontinuity and electrogram fractionation, with the degree
      of fractionation being dependent on activation rate and wavefront orientation
      with respect to the LB.

PMID- 24443508
TI  - The autotaxin-LPA axis emerges as a novel regulator of lymphocyte homing and
      inflammation.
AB  - Lysophosphatidic acid (LPA) is a pleiotropic lipid molecule with potent effects
      on cell growth and motility. Major progress has been made in recent years in
      deciphering the mechanisms of LPA generation and how it acts on target cells.
      Most research has been conducted in other disciplines, but emerging data indicate
      that LPA has an important role to play in immunity. A key discovery was that
      autotaxin (ATX), an enzyme previously implicated in cancer cell motility,
      generates extracellular LPA from the precursor lysophosphatidylcholine. Steady
      state ATX is expressed by only a few tissues, including high endothelial venules
      in lymph nodes, but inflammatory signals can upregulate ATX expression in
      different tissues. In this article, we review current thinking about the ATX/LPA
      axis in lymphocyte homing, as well as in models of allergic airway inflammation
      and asthma. New insights into the role of LPA in regulating immune responses
      should be forthcoming in the near future. 

PMID- 24443513
TI  - Antiretroviral treatment French guidelines 2013: economics influencing science.
AB  - Guidelines for the preferred choice of initial combination antiretroviral therapy
      in those living with HIV are provided by several national and international
      committees. Following the recent presentation of the 2013 French guidelines on
      antiretroviral therapy, there has been a debate regarding whether and/or how
      economics should influence guideline decisions and to what extent this should
      counterbalance valid scientific evidence. We discuss here the reasons for the
      unique nature of some of the proposals made by the French guidelines panel.
      Indeed, some recommendations are debatable. In the new French guidelines,
      economic considerations significantly influence and, in some instances, take
      precedence over the scientific evidence, leading to guidelines that are
      significantly different from those of other national and international
      committees. 

PMID- 24443514
TI  - An international, multicentre survey of beta-lactam antibiotic therapeutic drug
      monitoring practice in intensive care units.
AB  - OBJECTIVES: Emerging evidence supports the use of therapeutic drug monitoring
      (TDM) of beta-lactams for intensive care unit (ICU) patients to optimize drug
      exposure, although limited detail is available on how sites run this service in
      practice. This multicentre survey study was performed to describe the various
      approaches used for beta-lactam TDM in ICUs. METHODS: A questionnaire survey was
      developed to describe various aspects relating to the conduct of beta-lactam TDM
      in an ICU setting. Data sought included: beta-lactams chosen for TDM, inclusion
      criteria for selecting patients, blood sampling strategy, analytical methods,
      pharmacokinetic (PK)/pharmacodynamic (PD) targets and dose adjustment strategies.
      RESULTS: Nine ICUs were included in this survey. Respondents were either ICU or
      infectious disease physicians, pharmacists or clinical pharmacologists.
      Piperacillin (co-formulated with tazobactam) and meropenem (100% of units
      surveyed) were the beta-lactams most commonly subject to TDM, followed by
      ceftazidime (78%), ceftriaxone (43%) and cefazolin (43%). Different
      chromatographic and microbiological methods were used for assay of beta-lactam
      concentrations in blood and other biological fluids (e.g. CSF). There was
      significant variation in the PK/PD targets (100% fT>MIC up to 100% fT>4*MIC) and
      dose adjustment strategies used by each of the sites. CONCLUSIONS: Large
      variations were found in the type of beta-lactams tested, the patients selected
      for TDM and drug assay methods. Significant variation observed in the PK/PD
      targets and dose adjustment strategies used supports the need for further studies
      that robustly define PK/PD targets for ICU patients to ensure a greater
      consistency of practice for dose adjustment strategies for optimizing beta-lactam
      dosing with TDM.

PMID- 24443515
TI  - Outcomes of patients with peripartum cardiomyopathy who received mechanical
      circulatory support. Data from the Interagency Registry for Mechanically Assisted
      Circulatory Support.
AB  - BACKGROUND: We describe the characteristics and outcomes of peripartum
      cardiomyopathy (PPCMP) patients who received durable mechanical circulatory
      support and compared it with other etiologies of advanced heart failure. METHODS
      AND RESULTS: We analyzed 1258 women who were registered in Interagency Registry
      for Mechanically Assisted Circulatory Support between June 2006 and March 2012.
      Baseline characteristics, implant strategies, hemodynamics, echocardiographic
      data, and outcomes were compared. Ninety-nine women had PPCMP and 1159 had non
      PPCMP as primary diagnosis. PPCMP women were younger (P<0.001), more likely to be
      blacks, and had less comorbidities than non-PPCMP patients. PPCMP women had
      better survival than non-PPCMP women (P=0.01) with a 2-year survival of 83%.
      Multivariable risk factor adjustment analysis showed that the improved survival
      was likely because of younger age and fewer comorbidities. At 36 months, a
      proportion of 48% PPCMP received heart transplantation. Recovery occurred at a
      frequency of 6% and 2% in the PPCMP and non-PPCMP groups (P=0.1). Adverse event
      rates were similar in PPCMP and non-PPCMP patients except for higher cardiac
      arrhythmias and respiratory failure in the non-PPCMP in the first 3 months post
      implant. CONCLUSIONS: PPCMP women who receive durable mechanical circulatory
      support have a better survival than women with non-PPCPM. The improved survival
      observed in PPCMP is likely related to their fewer comorbidities and younger age.
      Myocardial recovery was uncommon and less than half of women with end-stage PPCPM
      received heart transplantation after 3 years of mechanical support.

PMID- 24443517
TI  - Geminivirus vectors deliver reagents for plant genome engineering.

PMID- 24443516
TI  - Cardiolipin-mediated mitochondrial dynamics and stress response in Arabidopsis.
AB  - Mitochondria are essential and dynamic organelles in eukaryotes. Cardiolipin (CL)
      is a key phospholipid in mitochondrial membranes, playing important roles in
      maintaining the functional integrity and dynamics of mitochondria in animals and
      yeasts. However, CL's role in plants is just beginning to be elucidated. In this
      study, we used Arabidopsis thaliana to examine the subcellular distribution of CL
      and CARDIOLIPIN SYNTHASE (CLS) and analyzed loss-of-function cls mutants for
      defects in mitochondrial morphogenesis and stress response. We show that CL
      localizes to mitochondria and is enriched at specific domains, and CLS targets to
      the inner membrane of mitochondria with its C terminus in the intermembrane
      space. Furthermore, cls mutants exhibit significantly impaired growth as well as
      altered structural integrity and morphogenesis of mitochondria. In contrast to
      animals and yeasts, in which CL's effect on mitochondrial fusion is more
      profound, Arabidopsis CL plays a dominant role in mitochondrial fission and
      exerts this function, at least in part, through stabilizing the protein complex
      of the major mitochondrial fission factor, DYNAMIN-RELATED PROTEIN3. CL also
      plays a role in plant responses to heat and extended darkness, stresses that
      induce programmed cell death. Our study has uncovered conserved and plant
      specific aspects of CL biology in mitochondrial dynamics and the organism
      response to environmental stresses. 

PMID- 24443518
TI  - ANGUSTIFOLIA3 binds to SWI/SNF chromatin remodeling complexes to regulate
      transcription during Arabidopsis leaf development.
AB  - The transcriptional coactivator ANGUSTIFOLIA3 (AN3) stimulates cell proliferation
      during Arabidopsis thaliana leaf development, but the molecular mechanism is
      largely unknown. Here, we show that inducible nuclear localization of AN3 during
      initial leaf growth results in differential expression of important
      transcriptional regulators, including GROWTH REGULATING FACTORs (GRFs). Chromatin
      purification further revealed the presence of AN3 at the loci of GRF5, GRF6,
      CYTOKININ RESPONSE FACTOR2, CONSTANS-LIKE5 (COL5), HECATE1 (HEC1), and
      ARABIDOPSIS RESPONSE REGULATOR4 (ARR4). Tandem affinity purification of protein
      complexes using AN3 as bait identified plant SWITCH/SUCROSE NONFERMENTING
      (SWI/SNF) chromatin remodeling complexes formed around the ATPases BRAHMA (BRM)
      or SPLAYED. Moreover, SWI/SNF ASSOCIATED PROTEIN 73B (SWP73B) is recruited by AN3
      to the promoters of GRF5, GRF3, COL5, and ARR4, and both SWP73B and BRM occupy
      the HEC1 promoter. Furthermore, we show that AN3 and BRM genetically interact.
      The data indicate that AN3 associates with chromatin remodelers to regulate
      transcription. In addition, modification of SWI3C expression levels increases
      leaf size, underlining the importance of chromatin dynamics for growth
      regulation. Our results place the SWI/SNF-AN3 module as a major player at the
      transition from cell proliferation to cell differentiation in a developing leaf.

PMID- 24443519
TI  - DNA replicons for plant genome engineering.
AB  - Sequence-specific nucleases enable facile editing of higher eukaryotic genomic
      DNA; however, targeted modification of plant genomes remains challenging due to
      ineffective methods for delivering reagents for genome engineering to plant
      cells. Here, we use geminivirus-based replicons for transient expression of
      sequence-specific nucleases (zinc-finger nucleases, transcription activator-like
      effector nucleases, and the clustered, regularly interspaced, short palindromic
      repeat/Cas system) and delivery of DNA repair templates. In tobacco (Nicotiana
      tabacum), replicons based on the bean yellow dwarf virus enhanced gene targeting
      frequencies one to two orders of magnitude over conventional Agrobacterium
      tumefaciens T-DNA. In addition to the nuclease-mediated DNA double-strand breaks,
      gene targeting was promoted by replication of the repair template and pleiotropic
      activity of the geminivirus replication initiator proteins. We demonstrate the
      feasibility of using geminivirus replicons to generate plants with a desired DNA
      sequence modification. By adopting a general plant transformation method,
      plantlets with a desired DNA change were regenerated in <6 weeks. These results,
      in addition to the large host range of geminiviruses, advocate the use of
      replicons for plant genome engineering. 

PMID- 24443521
TI  - Molecular classification of malignant pleural mesothelioma: identification of a
      poor prognosis subgroup linked to the epithelial-to-mesenchymal transition.
AB  - PURPOSE: Despite research efforts to develop more effective diagnostic and
      therapeutic approaches, malignant pleural mesothelioma (MPM) prognosis remains
      poor. The assessment of tumor response to therapy can be improved by a deeper
      phenotypical classification of the tumor, with emphasis on its clinico-biological
      heterogeneity. The identification of molecular profiles is a powerful approach to
      better define MPM subclasses and targeted therapies. EXPERIMENTAL DESIGN:
      Molecular subclasses were defined by transcriptomic microarray on 38 primary MPM
      cultures. A three-gene predictor, identified by quantitative reverse
      transcription PCR, was used to classify an independent series of 108 frozen tumor
      samples. Gene mutations were determined in BAP1, CDKN2A, CDKN2B, NF2, and TP53.
      Epithelial-to-mesenchymal transition (EMT) markers were studied at the mRNA and
      protein levels. RESULTS: Unsupervised hierarchical clustering on transcriptomic
      data defined two robust MPM subgroups (C1 and C2), closely related to prognosis
      and partly to histologic subtypes. All sarcomatoid/desmoplastic MPM were included
      in the C2 subgroup. Epithelioid MPM were found in both subgroups, with a worse
      survival prognosis in the C2 subgroup. This classification and its association
      with histologic subtypes and survival were validated in our independent series
      using the three-gene predictor. Similar subgroups were found after classification
      of other MPM series from transcriptomic public datasets. C1 subgroup exhibited
      more frequent BAP1 alterations. Pathway analysis revealed that EMT was
      differentially regulated between MPM subgroups. C2 subgroup is characterized by a
      mesenchymal phenotype. CONCLUSIONS: A robust classification of MPM that defines
      two subgroups of epithelioid MPM, characterized by different molecular profiles,
      gene alterations, and survival outcomes, was established.

PMID- 24443520
TI  - A wheat SIMILAR TO RCD-ONE gene enhances seedling growth and abiotic stress
      resistance by modulating redox homeostasis and maintaining genomic integrity.
AB  - Plant growth inhibition is a common response to salinity. Under saline
      conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression
      line, performs better than its parent wheat variety Jinan 177 (JN177) with
      respect to both seedling growth and abiotic stress tolerance. Furthermore, the
      endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to
      JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase
      (PARP) domain protein, was identified to be crucial for both aspects of its
      superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis
      thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the
      overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis
      promote the accumulation of ROS, mainly by enhancing the activity of NADPH
      oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the
      suppression of alternative oxidase expression. Moreover, it promotes the activity
      of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate
      ROS content and cellular redox homeostasis. sro1 is also found to be involved in
      the maintenance of genomic integrity. We show here that the wheat SRO has PARP
      activity; such activity could be manipulated to improve the growth of seedlings
      exposed to salinity stress by modulating redox homeostasis and maintaining
      genomic stability. 

PMID- 24443522
TI  - Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse
      responses to EGFR-TKI and crizotinib in relation to diverse receptors
      phosphorylation.
AB  - PURPOSE: We investigated the incidence of concomitant epidermal growth factor
      receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in
      Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses
      to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors.
      EXPERIMENTAL DESIGN: We screened 977 consecutive patients with NSCLC for the
      presence of concomitant EGFR mutations and ALK rearrangements by rapid
      amplification of cDNA ends-coupled PCR sequencing and FISH. Immunohistochemistry
      (IHC) and Western blotting were used to correlate the activation of EGFR, ALK,
      and downstream proteins with responses to EGFR-TKIs and crizotinib. RESULTS: The
      overall frequency of concomitant EGFR mutations and ALK rearrangements was 1.3%
      (13/977). EGFR/ALK co-alterations were found in 3.9% (13/336) EGFR-mutant and
      18.6% (13/70) ALK-rearranged patients. Ten tumors were treated with first-line
      EGFR-TKIs, with a response rate of 80% (8/10). Two tumors with high phospho-ALK
      levels and low phospho-EGFR levels achieved stable and progressive disease,
      respectively. Median progression-free survival was 11.2 months. Coexpression of
      mutant EGFR and ALK fusion proteins in the same tumor cell populations was
      detected by IHC. Two cases with high phospho-ALK levels treated with crizotinib
      achieved partial responses; two cases with low phospho-ALK levels had progressive
      or stable disease. CONCLUSION: ALK rearrangements and EGFR mutations could
      coexist in a small subgroup of NSCLC. Advanced pulmonary adenocarcinomas with
      such co-alterations could have diverse responses to EGFR-TKIs and crizotinib.
      Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR
      TKI and crizotinib.

PMID- 24443523
TI  - Cotargeting the PI3K and RAS pathways for the treatment of neuroendocrine tumors.
AB  - BACKGROUND: The precise involvement of the PI3K/mTOR and RAS/MEK pathways in
      carcinoid tumors is not well defined. Therefore, the purpose of our study was to
      evaluate the role these pathways play in carcinoid cell proliferation, apoptosis,
      and secretion and to determine the effects of combined treatment on carcinoid
      tumor inhibition. METHODS: The human neuroendocrine cell lines BON (pancreatic
      carcinoid), NCI-H727 (lung carcinoid), and QGP-1 (somatostatinoma) were treated
      with either the pan-PI3K inhibitor, BKM120, or the dual PI3K-mTOR inhibitor,
      BEZ235, alone or in combination with the MEK inhibitor, PD0325901; proliferation,
      apoptosis, and protein expression were assessed. Peptide secretion was evaluated
      in BON and QGP-1 cells. The antiproliferative effect of BEZ235, alone or combined
      with PD0325901, was then tested in vivo. RESULTS: Both BKM120 and BEZ235
      decreased proliferation and increased apoptosis; combination with PD0325901
      significantly enhanced the antineoplastic effects of either treatment alone. In
      contrast, neurotensin peptide secretion was markedly stimulated with BKM120
      treatment, but not BEZ235. The combination of BEZ235 + PD0325901 significantly
      inhibited the growth of BON xenografts without systemic toxicity. CONCLUSIONS:
      Both BKM120 and BEZ235 effectively inhibited neuroendocrine tumor (NET) cell
      proliferation and stimulated apoptosis. However, inhibition of the PI3K pathway
      alone with BKM120 significantly stimulated neurotensin peptide secretion; this
      did not occur with the dual inhibition of both PI3K and mTOR using BEZ235
      suggesting that this would be a more effective treatment regimen for NETs.
      Moreover, the combination of BEZ235 and the MEK inhibitor PD0325901 was a safe
      and more effective therapy in vivo compared with single agents alone.

PMID- 24443525
TI  - Antagonistic regulation of growth and immunity by the Arabidopsis basic helix
      loop-helix transcription factor homolog of brassinosteroid enhanced expression2
      interacting with increased leaf inclination1 binding bHLH1.
AB  - Plants need to finely balance resources allocated to growth and immunity to
      achieve optimal fitness. A tradeoff between pathogen-associated molecular pattern
      (PAMP)-triggered immunity (PTI) and brassinosteroid (BR)-mediated growth was
      recently reported, but more information about the underlying mechanisms is
      needed. Here, we identify the basic helix-loop-helix (bHLH) transcription factor
      homolog of brassinosteroid enhanced expression2 interacting with IBH1 (HBI1) as a
      negative regulator of PTI signaling in Arabidopsis (Arabidopsis thaliana). HBI1
      expression is down-regulated in response to different PAMPs. HBI1 overexpression
      leads to reduced PAMP-triggered responses. This inhibition correlates with
      reduced steady-state expression of immune marker genes, leading to increased
      susceptibility to the bacterium Pseudomonas syringae. Overexpression of the HBI1
      related bHLHs brassinosteroid enhanced expression2 (BEE2) and cryptochrome
      interacting bHLH (CIB1) partially inhibits immunity, indicating that BEE2 and
      CIB1 may act redundantly with HBI1. In contrast to its expression pattern upon
      PAMP treatment, HBI1 expression is enhanced by BR treatment. Also, HBI1
      overexpressing plants are hyperresponsive to BR and more resistant to the BR
      biosynthetic inhibitor brassinazole. HBI1 is nucleus localized, and a mutation in
      a conserved leucine residue within the first helix of the protein interaction
      domain impairs its function in BR signaling. Interestingly, HBI1 interacts with
      several inhibitory atypical bHLHs, which likely keep HBI1 under negative control.
      Hence, HBI1 is a positive regulator of BR-triggered responses, and the negative
      effect of PTI is likely due to the antagonism between BR and PTI signaling. This
      study identifies a novel component involved in the complex tradeoff between
      innate immunity and BR-regulated growth.

PMID- 24443524
TI  - Cytokinin antagonizes abscisic acid-mediated inhibition of cotyledon greening by
      promoting the degradation of abscisic acid insensitive5 protein in Arabidopsis.
AB  - In higher plants, seed germination is followed by postgerminative growth. One of
      the key developmental events during postgerminative growth is cotyledon greening,
      which enables a seedling to establish photosynthetic capacity. The plant
      phytohormone abscisic acid (ABA) plays a vital role by inhibiting seed
      germination and postgerminative growth in response to dynamically changing
      internal and environmental cues. It has been shown that abscisic acid
      insensitive5 (ABI5), a basic leucine zipper transcription factor, is an important
      factor in the regulation of the ABA-mediated inhibitory effect on seed
      germination and postgerminative growth. Conversely, the phytohormone cytokinin
      has been proposed to promote seed germination by antagonizing the ABA-mediated
      inhibitory effect. However, the underpinning molecular mechanism of cytokinin
      repressed ABA signaling is largely unknown. Here, we show that cytokinin
      specifically antagonizes ABA-mediated inhibition of cotyledon greening with
      minimal effects on seed germination in Arabidopsis (Arabidopsis thaliana). We
      found that the cytokinin-antagonized ABA effect is dependent on a functional
      cytokinin signaling pathway, mainly involved in the cytokinin receptor gene
      cytokinin response1/Arabidopsis histidine kinase4, downstream histidine
      phosphotransfer protein genes AHP2, AHP3, and AHP5, and a type B response
      regulator gene, ARR12, which genetically acts upstream of ABI5 to regulate
      cotyledon greening. Cytokinin has no apparent effect on the transcription of
      ABI5. However, cytokinin efficiently promotes the proteasomal degradation of ABI5
      in a cytokinin signaling-dependent manner. These results define a genetic pathway
      through which cytokinin specifically induces the degradation of ABI5 protein,
      thereby antagonizing ABA-mediated inhibition of postgerminative growth.

PMID- 24443526
TI  - A signaling pathway involving the diguanylate cyclase CelR and the response
      regulator DivK controls cellulose synthesis in Agrobacterium tumefaciens.
AB  - The production of cellulose fibrils is involved in the attachment of
      Agrobacterium tumefaciens to its plant host. Consistent with previous studies, we
      reported recently that a putative diguanylate cyclase, celR, is required for
      synthesis of this polymer in A. tumefaciens. In this study, the effects of celR
      and other components of the regulatory pathway of cellulose production were
      explored. Mutational analysis of celR demonstrated that the cyclase requires the
      catalytic GGEEF motif, as well as the conserved aspartate residue of a CheY-like
      receiver domain, for stimulating cellulose production. Moreover, a site-directed
      mutation within the PilZ domain of CelA, the catalytic subunit of the cellulose
      synthase complex, greatly reduced cellulose production. In addition, deletion of
      divK, the first gene of the divK-celR operon, also reduced cellulose production.
      This requirement for divK was alleviated by expression of a constitutively active
      form of CelR, suggesting that DivK acts upstream of CelR activation. Based on
      bacterial two-hybrid assays, CelR homodimerizes but does not interact with DivK.
      The mutation in divK additionally affected cell morphology, and this effect was
      complementable by a wild-type copy of the gene, but not by the constitutively
      active allele of celR. These results support the hypothesis that CelR is a bona
      fide c-di-GMP synthase and that the nucleotide signal produced by this enzyme
      activates CelA via the PilZ domain. Our studies also suggest that the DivK/CelR
      signaling pathway in Agrobacterium regulates cellulose production independent of
      cell cycle checkpoint systems that are controlled by divK. 

PMID- 24443527
TI  - Regulatory and functional diversity of methylmercaptopropionate coenzyme A
      ligases from the dimethylsulfoniopropionate demethylation pathway in Ruegeria
      pomeroyi DSS-3 and other proteobacteria.
AB  - The organosulfur compound dimethylsulfoniopropionate (DMSP) is produced by
      phytoplankton and is ubiquitous in the surface ocean. Once released from
      phytoplankton, marine bacteria degrade DMSP by either the cleavage pathway to
      form the volatile gas dimethylsulfide (DMS) or the demethylation pathway,
      yielding methanethiol (MeSH), which is readily assimilated or oxidized. The
      enzyme DmdB, a methylmercaptopropionate (MMPA)-coenzyme A (CoA) ligase, catalyzes
      the second step in the demethylation pathway and is a major regulatory point. The
      two forms of DmdB present in the marine roseobacter Ruegeria pomeroyi DSS-3,
      RPO_DmdB1 and RPO_DmdB2, and the single form in the SAR11 clade bacterium
      "Candidatus Pelagibacter ubique" HTCC1062, PU_DmdB1, were characterized in
      detail. DmdB enzymes were also examined from Ruegeria lacuscaerulensis ITI-1157,
      Pseudomonas aeruginosa PAO1, and Burkholderia thailandensis E264. The DmdB
      enzymes separated into two phylogenetic clades. All enzymes had activity with
      MMPA and were sensitive to inhibition by salts, but there was no correlation
      between the clades and substrate specificity or salt sensitivity. All Ruegeria
      species enzymes were inhibited by physiological concentrations (70 mM) of DMSP.
      However, ADP reversed the inhibition of RPO_DmdB1, suggesting that this enzyme
      was responsive to cellular energy charge. MMPA reversed the inhibition of
      RPO_DmdB2 as well as both R. lacuscaerulensis ITI-1157 DmdB enzymes, suggesting
      that a complex regulatory system exists in marine bacteria. In contrast, the
      DmdBs of the non-DMSP-metabolizing P. aeruginosa PAO1 and B. thailandensis E264
      were not inhibited by DMSP, suggesting that DMSP inhibition is a specific
      adaptation of DmdBs from marine bacteria. 

PMID- 24443528
TI  - Salinity-dependent impacts of ProQ, Prc, and Spr deficiencies on Escherichia coli
      cell structure.
AB  - ProQ is a cytoplasmic protein with RNA chaperone activities that reside in FinO-
      and Hfq-like domains. Lesions at proQ decrease the level of the osmoregulatory
      glycine betaine transporter ProP. Lesions at proQ eliminated ProQ and Prc, the
      periplasmic protease encoded by the downstream gene prc. They dramatically slowed
      the growth of Escherichia coli populations and altered the morphologies of E.
      coli cells in high-salinity medium. ProQ and Prc deficiencies were associated
      with different phenotypes. ProQ-deficient bacteria were elongated unless glycine
      betaine was provided. High-salinity cultures of Prc-deficient bacteria included
      spherical cells with an enlarged periplasm and an eccentric nucleoid. The
      nucleoid-containing compartment was bounded by the cytoplasmic membrane and
      peptidoglycan. This phenotype was not evident in bacteria cultivated at low or
      moderate salinity, nor was it associated with murein lipoprotein (Lpp)
      deficiency, and it differed from those elicited by the MreB inhibitor A-22 or the
      FtsI inhibitor aztreonam at low or high salinity. It was suppressed by deletion
      of spr, which encodes one of three murein hydrolases that are redundantly
      essential for enlargement of the murein sacculus. Prc deficiency may alter
      bacterial morphology by impairing control of Spr activity at high salinity. ProQ
      and Prc deficiencies lowered the ProP activity of bacteria cultivated at moderate
      salinity by approximately 70% and 30%, respectively, but did not affect other
      osmoregulatory functions. The effects of ProQ and Prc deficiencies on ProP
      activity are indirect, reflecting their roles in the maintenance of cell
      structure. 

PMID- 24443529
TI  - Differential activation of Staphylococcus aureus heme detoxification machinery by
      heme analogues.
AB  - The reactive nature of heme enables its use as an enzymatic cofactor while
      rendering excess heme toxic. The importance of heme detoxification machinery is
      highlighted by the presence of various types of these homeostatic systems in Gram
      positive and Gram-negative microorganisms. A number of pathogens possess
      orthologs of the HssRS/HrtAB heme detoxification system, underscoring a potential
      role this system plays in the survival of bacteria in heme-rich environments such
      as the vertebrate host. In this work, we sought to determine the role of this
      system in protection against metalloporphyrin heme analogues identified by
      previous studies as antimicrobial agents. Our findings demonstrate that only
      toxic metalloporphyrins maximally activate expression of the Staphylococcus
      aureus heme detoxification system, suggesting that the sensing mechanism of HssRS
      might require a component of the associated toxicity rather than or in addition
      to the metalloporphyrin itself. We further establish that only a subset of toxic
      metalloporphyrins elicit the oxidative damage previously shown to be a
      significant component of heme toxicity whereas all toxic noniron
      metalloporphyrins inhibit bacterial respiration. Finally, we demonstrate that,
      despite the fact that toxic metalloporphyrin treatment induces expression of S.
      aureus heme detoxification machinery, the HrtAB heme export pump is unable to
      detoxify most of these molecules. The ineffectiveness of HrtAB against toxic heme
      analogues provides an explanation for their increased antimicrobial activity
      relative to heme. Additionally, these studies define the specificity of
      HssRS/HrtAB, which may provide future insight into the biochemical mechanisms of
      these systems. 

PMID- 24443530
TI  - Defining the region of Bacillus subtilis SpoIIIJ that is essential for its
      sporulation-specific function.
AB  - Proteins of the YidC/OxaI/Alb3 family play a crucial role in the insertion,
      folding, and/or assembly of membrane proteins in prokaryotes and eukaryotes.
      Bacillus subtilis has two YidC-like proteins, denoted SpoIIIJ and YqjG. SpoIIIJ
      and YqjG are largely exchangeable in function, but SpoIIIJ has a unique role in
      sporulation, while YqjG stimulates competence development. To obtain more insight
      into the regions important for the sporulation specificity of SpoIIIJ, a series
      of SpoIIIJ/YqjG chimeras was constructed. These chimeras were tested for
      functionality during vegetative growth and for their ability to complement the
      sporulation defect of a spoIIIJ deletion strain. The data suggest an important
      role for the domain comprising transmembrane segment 2 (TMS2) and its flanking
      loops in sporulation specificity, with lesser contributions to specificity by
      TMS1 and TMS3. 

PMID- 24443531
TI  - Expression and targeting of secreted proteins from Chlamydia trachomatis.
AB  - Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a
      vacuole termed the inclusion. Many of the interactions of chlamydiae with the
      host cell are dependent upon bacterial protein synthesis and presumably exposure
      of these proteins to the cytosol. Because of the dearth of genetic tools for
      chlamydiae, previous studies examining secreted proteins required the use of
      heterologous bacterial systems. Recent advances in genetic manipulation of
      chlamydia now allow for transformation of the bacteria with plasmids. We describe
      here a shuttle vector system, pBOMB4, that permits expression of recombinant
      proteins under constitutive or conditional promoter control. We show that the
      inclusion membrane protein IncD is secreted in a type III-dependent manner from
      Yersinia pseudotuberculosis and also secreted from C. trachomatis in infected
      cells where it localizes appropriately to the inclusion membrane. IncD truncated
      of the first 30 amino acids containing the secretion signal is no longer secreted
      and is retained by the bacteria. Cytosolic exposure of secreted proteins can be
      confirmed by using CyaA, GSK, or microinjection assays. A protein predicted to be
      retained within the bacteria, NrdB is indeed localized to the chlamydia. In
      addition, we have shown that the chlamydial effector protein, CPAF, which is
      secreted into the host cell cytosol by a Sec-dependent pathway, also accesses the
      cytosol when expressed from this system. These assays should prove useful to
      assess the secretion of other chlamydial proteins that are potentially exposed to
      the cytosol of the host cell. 

PMID- 24443532
TI  - Parallel pathways for nitrite reduction during anaerobic growth in Thermus
      thermophilus.
AB  - Respiratory reduction of nitrate and nitrite is encoded in Thermus thermophilus
      by the respective transferable gene clusters. Nitrate is reduced by a
      heterotetrameric nitrate reductase (Nar) encoded along transporters and
      regulatory signal transduction systems within the nitrate respiration conjugative
      element (NCE). The nitrite respiration cluster (nic) encodes homologues of
      nitrite reductase (Nir) and nitric oxide reductase (Nor). The expression and role
      of the nirSJM genes in nitrite respiration were analyzed. The three genes are
      expressed from two promoters, one (nirSp) producing a tricistronic mRNA under
      aerobic and anaerobic conditions and the other (nirJp) producing a bicistronic
      mRNA only under conditions of anoxia plus a nitrogen oxide. As for its nitrite
      reductase homologues, NirS is expressed in the periplasm, has a covalently bound
      heme c, and conserves the heme d1 binding pocket. NirJ is a cytoplasmic protein
      likely required for heme d1 synthesis and NirS maturation. NirM is a soluble
      periplasmic homologue of cytochrome c552. Mutants defective in nirS show normal
      anaerobic growth with nitrite and nitrate, supporting the existence of an
      alternative Nir in the cells. Gene knockout analysis of different candidate genes
      did not allow us to identify this alternative Nir protein but revealed the
      requirement for Nar in NirS-dependent and NirS-independent nitrite reduction. As
      the likely role for Nar in the process is in electron transport through its
      additional cytochrome c periplasmic subunit (NarC), we concluded all the Nir
      activity takes place in the periplasm by parallel pathways. 

PMID- 24443533
TI  - Two glycine riboswitches activate the glycine cleavage system essential for
      glycine detoxification in Streptomyces griseus.
AB  - The glycine cleavage (GCV) system catalyzes the oxidative cleavage of glycine
      into CO2, NH4(+), and a methylene group, which is accepted by tetrahydrofolate
      (THF) to form N(5),N(10)-methylene-THF. Streptomyces griseus contains gcvP and
      the gcvT-gcvH operon, which encode three intrinsic components of the GCV system.
      We identified the transcriptional start sites of gcvTH and gcvP and found
      putative glycine riboswitches in their 5' untranslated regions (5' UTRs). The
      ratios of the transcripts of the gcvT and gcvP coding sequences (CDSs) to those
      of the respective 5' UTRs were significantly higher in the presence of glycine in
      the wild-type strain. However, the levels of gcvT and gcvP CDS transcripts were
      not increased by glycine in the respective 5' UTR deletion mutants. A reporter
      gene assay showed that a transcriptional terminator exists in the 5' UTR of
      gcvTH. Furthermore, by an in-line probing assay, we confirmed that glycine bound
      directly to the putative riboswitch RNAs. These results indicate that the S.
      griseus glycine riboswitches enhance transcriptional read-through to the
      downstream CDSs, like known glycine riboswitches in other bacteria. We examined
      the growth of three mutants in which either or both of the gcvTH and gcvP 5' UTRs
      were deleted. Like the wild-type strain, all mutants grew vigorously in a medium
      containing 0.9% glucose as a carbon source. However, the mutants showed severely
      restricted growth in a medium containing 0.9% glucose and 1% glycine, while the
      wild-type strain grew normally. This indicates that glycine has a growth
      inhibitory effect and that the GCV system plays a critical role in glycine
      detoxification in S. griseus. 

PMID- 24443534
TI  - RecD2 helicase limits replication fork stress in Bacillus subtilis.
AB  - DNA helicases have important roles in genome maintenance. The RecD helicase has
      been well studied as a component of the heterotrimeric RecBCD helicase-nuclease
      enzyme important for double-strand break repair in Escherichia coli.
      Interestingly, many bacteria lack RecBC and instead contain a RecD2 helicase,
      which is not known to function as part of a larger complex. Depending on the
      organism studied, RecD2 has been shown to provide resistance to a broad range of
      DNA-damaging agents while also contributing to mismatch repair (MMR). Here we
      investigated the importance of Bacillus subtilis RecD2 helicase to genome
      integrity. We show that deletion of recD2 confers a modest increase in the
      spontaneous mutation rate and that the mutational signature in DeltarecD2 cells
      is not consistent with an MMR defect, indicating a new function for RecD2 in B.
      subtilis. To further characterize the role of RecD2, we tested the deletion
      strain for sensitivity to DNA-damaging agents. We found that loss of RecD2 in B.
      subtilis sensitized cells to several DNA-damaging agents that can block or impair
      replication fork movement. Measurement of replication fork progression in vivo
      showed that forks collapse more frequently in DeltarecD2 cells, supporting the
      hypothesis that RecD2 is important for normal replication fork progression.
      Biochemical characterization of B. subtilis RecD2 showed that it is a 5'-3'
      helicase and that it directly binds single-stranded DNA binding protein.
      Together, our results highlight novel roles for RecD2 in DNA replication which
      help to maintain replication fork integrity during normal growth and when forks
      encounter DNA damage. 

PMID- 24443535
TI  - The ssbL gene harbored by the ColV plasmid of an Escherichia coli neonatal
      meningitis strain is an auxiliary virulence factor boosting the production of
      siderophores through the shikimate pathway.
AB  - The ability to capture iron is a challenge for most bacteria. The neonatal
      meningitis Escherichia coli strain S88 possesses several iron uptake systems,
      notably including siderophores. Transcriptional analysis of the ColV plasmid pS88
      has shown strong induction of a previously undescribed gene with low identity to
      three E. coli chromosomal genes encoding phospho-2-dehydro-3-deoxyheptonate
      aldolases involved in aromatic amino acid and catecholate/phenolate siderophore
      biosynthesis through the shikimate pathway. Here, we investigated the role of
      this gene, ssbLp (ssbL carried on the plasmid), in siderophore biosynthesis and,
      consequently, in S88 virulence. We constructed an S88 mutant designated S88
      DeltassbLp, which exhibited reduced growth under low-iron conditions compared to
      the wild-type strain. Liquid chromatography-mass spectroscopy analysis of culture
      supernatants showed that the mutant secreted significantly smaller amounts of
      enterobactin, salmochelin SX, and yersiniabactin than the wild-type strain. The
      mutant was also less virulent in a neonatal rat sepsis model, with significantly
      lower bacteremia and mortality. Supplementation with chorismate, the final
      product of the shikimate pathway, restored the wild-type phenotype in vitro. In a
      collection of human extraintestinal E. coli isolates, we found that ssbL was
      present only in strains harboring the iro locus, encoding salmochelins, and was
      located either on the chromosome or on plasmids. Acquisition of the iro locus has
      been accompanied by acquisition of the auxiliary gene ssbL, which boosts the
      metabolic pathway essential for catecholate/phenolate siderophore biosynthesis
      and could represent potential therapeutic targets. 

PMID- 24443541
TI  - Failure of miltefosine in visceral leishmaniasis is associated with low drug
      exposure.
AB  - BACKGROUND: Recent reports indicated high miltefosine treatment failure rates for
      visceral leishmaniasis (VL) on the Indian subcontinent. To further explore the
      pharmacological factors associated with these treatment failures, a population
      pharmacokinetic-pharmacodynamic study was performed to examine the relationship
      between miltefosine drug exposure and treatment failure in a cohort of Nepalese
      patients with VL. METHODS: Miltefosine steady-state blood concentrations at the
      end of treatment were analyzed using liquid chromatography tandem mass
      spectrometry. A population pharmacokinetic-pharmacodynamic analysis was performed
      using nonlinear mixed-effects modeling and a logistic regression model.
      Individual estimates of miltefosine exposure were explored for their relationship
      with treatment failure. RESULTS: The overall probability of treatment failure was
      21%. The time that the blood concentration was >10 times the half maximal
      effective concentration of miltefosine (median, 30.2 days) was significantly
      associated with treatment failure: each 1-day decrease in miltefosine exposure
      was associated with a 1.08-fold (95% confidence interval, 1.01-1.17) increased
      odds of treatment failure. CONCLUSIONS: Achieving a sufficient exposure to
      miltefosine is a significant and critical factor for VL treatment success,
      suggesting an urgent need to evaluate the recently proposed optimal allometric
      miltefosine dosing regimen. This study establishes the first evidence for a drug
      exposure-effect relationship for miltefosine in the treatment of VL.

PMID- 24443542
TI  - Endothelial activation and dysfunction in the pathogenesis of microvascular
      obstruction in severe malaria--a viable target for therapeutic adjunctive
      intervention.

PMID- 24443543
TI  - Emergence of hypervirulent mutants resistant to early clearance during systemic
      serotype 1 pneumococcal infection in mice and humans.
AB  - BACKGROUND: Streptococcus pneumoniae serotype 1 has a high likelihood of causing
      invasive disease. Serotype 1 isolates belonging to CC228 are associated with low
      mortality, while CC217 isolates exhibit high mortality in patients. METHODS:
      Clinical pneumococcal isolates and mutants were evaluated in wild-type C57BL/6
      mice, macrophage-depleted mice, neutrophil-depleted mice, and SIGN-R1 knockout
      mice. In vitro models included binding and phagocytosis by THP-1 cells, capsule
      measurements, hydrogen peroxide production, and viability assays. RESULTS: During
      early systemic infection in mice with serotype 1, large-colony variants appeared
      in blood. Similar large colonies were found in blood specimens from patients with
      invasive disease. Large morphotypes contained higher numbers of viable bacteria,
      grew faster, produced no or little hydrogen peroxide, and contained mutations in
      the spxB gene. spxB mutants were considerably more virulent in wild-type mice,
      less susceptible to early host clearance than wild-type strains after intravenous
      infection, but impaired in colonization. spxB mutants were less efficiently
      phagocytosed by macrophages than wild-type bacteria, which, in contrast to spxB
      mutants, caused more-severe disease when macrophages or SIGN-R1 were depleted.
      CONCLUSIONS: Hypervirulent spxB mutants are selected in both mice and patients
      and are resistant to early macrophage-mediated clearance.

PMID- 24443544
TI  - Sequential acquisition of T cells and antibodies to nontyphoidal Salmonella in
      Malawian children.
AB  - BACKGROUND: Salmonella Typhimurium (STm) remain a prominent cause of bacteremia
      in sub-Saharan Africa. Complement-fixing antibodies to STm develop by 2 years of
      age. We hypothesized that STm-specific CD4+ T cells develop alongside this
      process. METHODS: Eighty healthy Malawian children aged 0-60 months were
      recruited. STm-specific CD4+ T cells producing interferon gamma, tumor necrosis
      factor alpha, and interleukin 2 were quantified using intracellular cytokine
      staining. Antibodies to STm were measured by serum bactericidal activity (SBA)
      assay, and anti-STm immunoglobulin G antibodies by enzyme-linked immunosorbent
      assay. RESULTS: Between 2006 and 2011, STm bacteremias were detected in 449
      children <5 years old. STm-specific CD4+ T cells were acquired in infancy, peaked
      at 14 months, and then declined. STm-specific SBA was detectable in newborns,
      declined in the first 8 months, and then increased to a peak at age 35 months.
      Acquisition of SBA correlated with acquisition of anti-STm-lipopolysaccharide
      (LPS) immunoglobulin G (r = 0.329 [95% confidence interval, .552-.062]; P = .01)
      but not anti-STm-outer membrane protein or anti-STm-flagellar protein (FliC).
      CONCLUSIONS: Acquisition of STm-specific CD4+ T cells in early childhood is
      consistent with early exposure to STm or cross-reactive protein antigens priming
      this T-cell development. STm-specific CD4+ T cells seem insufficient to protect
      against invasive nontyphoidal Salmonella disease, but sequential acquisition of
      SBA to STm LPS is associated with a decline in its incidence.

PMID- 24443545
TI  - Different effects of whole-cell and acellular vaccines on Bordetella
      transmission.
AB  - BACKGROUND: Vaccine development has largely focused on the ability of vaccines to
      reduce disease in individual hosts, with less attention to assessing the
      vaccine's effects on transmission between hosts. Current acellular vaccines
      against Bordetella pertussis are effective in preventing severe disease but have
      little effect on less severe coughing illness that can mediate transmission.
      METHODS: Using mice that are natural host's of Bordetella bronchiseptica, we
      determined the effects of vaccination on shedding and transmission of this
      pathogen. RESULTS: Vaccination with heat-killed whole-cell B. bronchiseptica or
      B. pertussis inhibited shedding of B. bronchiseptica. Differences in neutrophil
      and B-cell recruitment distinguished sham-vaccine from whole-cell-----vaccine
      responses and correlated with shedding output. Both B and T cells were essential
      for vaccine-induced control of shedding. Adoptive transfer of antibodies was able
      to limit shedding, while depletion of CD4(+) T cells led to increased shedding in
      vaccinated mice. Finally, whole-cell vaccination was able to prevent
      transmission, but an acellular vaccine that effectively controls disease failed
      to control shedding and transmission. CONCLUSIONS: Our results highlight
      discrepancies between whole-cell and acellular vaccination that could contribute
      to the increased incidence of B. pertussis infection since the transition to the
      use of acellular vaccination.

PMID- 24443546
TI  - Clinical outcomes among persons with pulmonary tuberculosis caused by
      Mycobacterium tuberculosis isolates with phenotypic heterogeneity in results of
      drug-susceptibility tests.
AB  - BACKGROUND: Patients with multidrug-resistant (MDR) tuberculosis may have
      phenotypic heterogeneity in results of drug-susceptibility tests (DSTs). However,
      the impact of this on clinical outcomes among patients treated for MDR
      tuberculosis is unknown. METHODS: Phenotypic DST heterogeneity was defined as
      presence of at least 1 Mycobacterium tuberculosis isolate susceptible to
      rifampicin and isoniazid recovered <3 months after MDR tuberculosis treatment
      initiation from a patient with previous documented tuberculosis due to M.
      tuberculosis resistant to at least rifampicin and isoniazid. The primary outcome
      was defined as good (ie, cure or treatment completion) or poor (ie, treatment
      failure, treatment default, or death). A secondary outcome was time to culture
      conversion. Cox proportional hazard models were used to determine the association
      between phenotypic DST heterogeneity and outcomes. RESULTS: Phenotypic DST
      heterogeneity was identified in 33 of 475 patients (7%) with MDR tuberculosis.
      Poor outcome occurred in 126 patients (28%). Overall, patients with MDR
      tuberculosis who had phenotypic DST heterogeneity were at greater risk of poor
      outcome than those with MDR tuberculosis but no phenotypic DST heterogeneity
      (adjusted hazard ratio [aHR], 2.1; 95% confidence interval [CI], 1.2-3.6). Among
      HIV-infected patients with MDR tuberculosis, the adjusted hazard for a poor
      outcome for those with phenotypic DST heterogeneity was 2.4 (95% CI, 1.3-4.2)
      times that for those without phenotypic DST heterogeneity, whereas among HIV
      negative patients with MDR tuberculosis, the adjusted hazard for those with
      phenotypic DST heterogeneity was 1.5 (95% CI, .5-4.3) times that for those
      without phenotypic DST heterogeneity. HIV-infected patients with MDR tuberculosis
      with phenotypic DST heterogeneity also had a longer time to culture conversion
      than with HIV-infected patients with MDR tuberculosis without phenotypic DST
      heterogeneity (aHR, 2.9; 95% CI, 1.4-6.0). CONCLUSIONS: Phenotypic DST
      heterogeneity among persons with HIV infection who are being treated for MDR
      tuberculosis is associated with poor outcomes and longer times to culture
      conversion.

PMID- 24443548
TI  - Human antibodies stop dengue virus by jamming its mechanics.

PMID- 24443547
TI  - Low-frequency nevirapine (NVP)-resistant HIV-1 variants are not associated with
      failure of antiretroviral therapy in women without prior exposure to single-dose
      NVP.
AB  - BACKGROUND: Low-frequency nevirapine (NVP)-resistant variants have been
      associated with virologic failure (VF) of initial NVP-based combination
      antiretroviral therapy (cART) in women with prior exposure to single-dose NVP
      (sdNVP). We investigated whether a similar association exists in women without
      prior sdNVP exposure. METHODS: Pre-cART plasma was analyzed by allele-specific
      polymerase chain reaction to quantify NVP-resistant mutants in human
      immunodeficiency virus-infected African women without prior sdNVP who were
      starting first-line NVP-based cART in the OCTANE/A5208 trial 2. Associations
      between NVP-resistant mutants and VF or death were determined and compared with
      published results from women participating in the OCTANE/A5208 trial 1 who had
      taken sdNVP and initiated NVP-based cART. RESULTS: Pre-cART NVP-resistant
      variants were detected in 18% (39/219) of women without prior sdNVP exposure,
      compared to 45% (51/114) with prior sdNVP exposure (P < .001). Among women
      without prior sdNVP exposure, 8 of 39 (21%) with NVP-resistant variants
      experienced VF or death vs 31 of 180 (17%) without such variants (P = .65); this
      compares with 21 of 51 (41%) vs 9 of 63 (14%) among women with prior exposure (P
      = .001). CONCLUSIONS: The risk of VF on NVP-based cART from NVP-resistant
      variants differs between sdNVP-exposed and -unexposed women. This difference may
      be driven by drug-resistance mutations emerging after sdNVP exposure that are
      linked on the same viral genome. CLINICAL TRIALS REGISTRATION: NCT00089505.

PMID- 24443549
TI  - An iron curtain in the Atlantic Ocean forms a biogeochemical divide.

PMID- 24443550
TI  - Searching for missing heritability: designing rare variant association studies.
AB  - Genetic studies have revealed thousands of loci predisposing to hundreds of human
      diseases and traits, revealing important biological pathways and defining novel
      therapeutic hypotheses. However, the genes discovered to date typically explain
      less than half of the apparent heritability. Because efforts have largely focused
      on common genetic variants, one hypothesis is that much of the missing
      heritability is due to rare genetic variants. Studies of common variants are
      typically referred to as genomewide association studies, whereas studies of rare
      variants are often simply called sequencing studies. Because they are actually
      closely related, we use the terms common variant association study (CVAS) and
      rare variant association study (RVAS). In this paper, we outline the similarities
      and differences between RVAS and CVAS and describe a conceptual framework for the
      design of RVAS. We apply the framework to address key questions about the sample
      sizes needed to detect association, the relative merits of testing disruptive
      alleles vs. missense alleles, frequency thresholds for filtering alleles, the
      value of predictors of the functional impact of missense alleles, the potential
      utility of isolated populations, the value of gene-set analysis, and the utility
      of de novo mutations. The optimal design depends critically on the selection
      coefficient against deleterious alleles and thus varies across genes. The
      analysis shows that common variant and rare variant studies require similarly
      large sample collections. In particular, a well-powered RVAS should involve
      discovery sets with at least 25,000 cases, together with a substantial
      replication set. 

PMID- 24443552
TI  - A general approach to site-specific antibody drug conjugates.
AB  - Using an expanded genetic code, antibodies with site-specifically incorporated
      nonnative amino acids were produced in stable cell lines derived from a CHO cell
      line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model
      systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime
      bond formation between ketones on the side chain of the incorporated nonnative
      amino acid and hydroxylamine functionalized monomethyl auristatin D with either
      protease-cleavable or noncleavable linkers. When noncleavable linkers were used,
      these conjugates were highly stable and displayed improved in vitro efficacy as
      well as in vivo efficacy and pharmacokinetic stability in rodent models relative
      to conventional antibody drug conjugates conjugated through either engineered
      surface-exposed or reduced interchain disulfide bond cysteine residues. The
      advantages of the oxime-bonded, site-specific NDCs were even more apparent when
      low-antigen-expressing (2+) target cell lines were used in the comparative
      studies. NDCs generated with protease-cleavable linkers demonstrated that the
      site of conjugation had a significant impact on the stability of these rationally
      designed prodrug linkers. In a single-dose rat toxicology study, a site-specific
      anti-Her2 NDC was well tolerated at dose levels up to 90 mg/kg. These experiments
      support the notion that chemically defined antibody conjugates can be synthesized
      in commercially relevant yields and can lead to antibody drug conjugates with
      improved properties relative to the heterogeneous conjugates formed by
      nonspecific chemical modification. 

PMID- 24443553
TI  - Rough parameter dependence in climate models and the role of Ruelle-Pollicott
      resonances.
AB  - Despite the importance of uncertainties encountered in climate model simulations,
      the fundamental mechanisms at the origin of sensitive behavior of long-term model
      statistics remain unclear. Variability of turbulent flows in the atmosphere and
      oceans exhibits recurrent large-scale patterns. These patterns, while evolving
      irregularly in time, manifest characteristic frequencies across a large range of
      time scales, from intraseasonal through interdecadal. Based on modern spectral
      theory of chaotic and dissipative dynamical systems, the associated low-frequency
      variability may be formulated in terms of Ruelle-Pollicott (RP) resonances. RP
      resonances encode information on the nonlinear dynamics of the system, and an
      approach for estimating them--as filtered through an observable of the system--is
      proposed. This approach relies on an appropriate Markov representation of the
      dynamics associated with a given observable. It is shown that, within this
      representation, the spectral gap--defined as the distance between the subdominant
      RP resonance and the unit circle--plays a major role in the roughness of
      parameter dependences. The model statistics are the most sensitive for the
      smallest spectral gaps; such small gaps turn out to correspond to regimes where
      the low-frequency variability is more pronounced, whereas autocorrelations decay
      more slowly. The present approach is applied to analyze the rough parameter
      dependence encountered in key statistics of an El-Nino-Southern Oscillation model
      of intermediate complexity. Theoretical arguments, however, strongly suggest that
      such links between model sensitivity and the decay of correlation properties are
      not limited to this particular model and could hold much more generally.

PMID- 24443554
TI  - Does diffusion of horse-related military technologies explain spatiotemporal
      patterns of social complexity 1500 BCE-AD 1500?

PMID- 24443555
TI  - A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration
      of regulatory T cells.
AB  - Tregs (Foxp3+CD4+) are enriched in tumors to foster a tolerant microenvironment
      that inhibits antitumor immune response. IL-27 is reported to regulate the
      development and function of Tregs in vitro and in vivo; however, the effects of
      endogenous IL-27 on Tregs in the tumor microenvironment remain elusive. We
      demonstrated that in the absence of DC-derived IL-27, Tregs were decreased
      significantly in transplanted B16 melanoma, transplanted EL-4 lymphoma, and MCA
      induced fibrosarcoma by using IL-27p28 conditional KO mice. Further studies
      revealed that IL-27 promoted the expression of CCL22, which is established to
      mediate the recruitment of peripheral Tregs into tumors. Tumor-associated DCs
      were identified as the major source of CCL22 in tumor sites, and IL-27 could
      induce CCL22 expression in an IL-27R-dependent manner. Intratumoral
      reconstitution of rmCCL22 or rmIL-27, but not rmIL-27p28, significantly restored
      the tumor infiltration of Tregs in IL-27p28 KO mice. Correlated with a decreased
      number of Tregs, tumor-infiltrating CD4 T cells were found to produce much more
      IFN-gamma in IL-27p28 KO mice, which highlighted the physiological importance of
      Tregs in suppressing an antitumor immune response. Overall, our results
      identified a novel mechanism of action of IL-27 on Tregs in the context of
      cancers.

PMID- 24443556
TI  - A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation
      of STAT1 ser727 phosphorylation in mouse macrophages.
AB  - PHLPP1 is a novel tumor suppressor, but its role in the regulation of innate
      immune responses, which are frequently dysregulated in cancer, is unexplored.
      Here, we report that LPS attenuated PHLPP1 expression at mRNA and protein levels
      in immune cells, suggesting its involvement in immune responses. To test this, we
      overexpressed PHLPP1 in RAW 264.7 macrophages and observed a dramatic reduction
      in LPS/IFN-gamma-induced iNOS expression. Conversely, silencing of PHLPP1 by
      siRNA or by shRNA robustly augmented LPS/IFN-gamma-induced iNOS expression. qPCR
      and iNOS promoter reporter experiments showed that PHLPP1 inhibited iNOS
      transcription. Mechanistic analysis revealed that PHLPP1 suppressed LPS/IFN-gamma
      induced phosphorylation of ser727 STAT1; however, the underlying mechanisms
      differed. PHLPP1 reduced IFN-gamma-stimulated but not LPS-induced ERK1/2
      phosphorylation, and inhibition of ERK1/2 abolished IFN-gamma-induced ser727
      STAT1 phosphorylation and iNOS expression. In contrast, PHLPP1 knockdown
      augmented LPS-induced but not IFN-gamma-elicited p38 phosphorylation. Blockade of
      p38 abolished LPS-stimulated phosphorylation of ser727 STAT1 and iNOS expression.
      Furthermore, PHLPP1 suppressed LPS-induced phosphorylation of tyr701 STAT1 by
      dampening p38-dependent IFN-beta feedback. Collectively, our data demonstrate for
      the first time that PHLPP1 plays a vital role in restricting innate immune
      responses of macrophages, and further studies may show it to be a potential
      therapeutic target within the context of dysregulated macrophage activity.

PMID- 24443557
TI  - Factors that trigger emergency physicians to contact a poison centre: findings
      from a Swiss study.
AB  - OBJECTIVE: Poison centres offer rapid and comprehensive support for emergency
      physicians managing poisoned patients. This study investigates institutional,
      case-specific and poisoning-specific factors which influence the decision of
      emergency physicians to contact a poison centre. METHODS: Retrospective,
      consecutive review of all poisoning-related admissions to the emergency
      departments (EDs) of a primary care hospital and a university hospital-based
      tertiary referral centre during 2007. Corresponding poison centre consultations
      were extracted from the poison centre database. Data were matched and analysed by
      logistic regression and generalised linear mixed models. RESULTS: 545 poisonings
      were treated in the participating EDs (350 (64.2%) in the tertiary care centre,
      195 (35.8%) in the primary care hospital). The poison centre was consulted in 62
      (11.4%) cases (38 (61.3%) by the tertiary care centre and 24 (38.7%) by the
      primary care hospital). Factors significantly associated with poison centre
      consultation included gender (female vs male) (OR 2.99; 95% CI 1.69 to 5.29;
      p<0.001), number of ingested substances (>1 vs 1) (OR 2.84; 95% CI 1.65 to 4.9;
      p<0.001) and situation (accidental vs intentional) (OR 2.76; 95% CI 1.05 to 7.25;
      p=0.039). In contrast, age, medical history and hospital size did not influence
      poison centre consultation. Poison centre consultation was significantly higher
      during the week, and significantly less during night shifts. The poison centre
      was consulted significantly more when patients were admitted to intensive care
      units (OR 5.81; 95% CI 3.25 to 10.37; p<0.001). Asymptomatic and severe versus
      mild cases were associated with more frequent consultation (OR 4.48; 95% CI 1.78
      to 11.26; p=0.001 and OR 2.76; 95% CI 1.42 to 5.38; p=0.003). CONCLUSIONS: We
      found low rates of poison centre consultation by emergency physicians. It appears
      that intensive care unit admission and other factors reflecting either complexity
      or uncertainty of the clinical situation are the strongest predictors for poison
      centre consultation. Hospital size did not influence referral behaviour.

PMID- 24443558
TI  - Evaluation of the extent of ketamine-induced uropathy: the role of CT urography.
AB  - BACKGROUND: With growing ketamine abuse, ketamine-induced uropathy (KIU) has
      become more prevalent in recent years. This research evaluates the presence,
      distribution and extent of KIU in the upper and lower urinary tracts by
      retrospectively reviewing CT urography (CTU) images. METHODS: Patients diagnosed
      with KIU who underwent CT scanning from 1 January 2006 to 31 December 2011 were
      recruited. The CT protocols included three-phase CTU in six patients, split-bolus
      CTU in 17, two-phase CT in one and unenhanced CT in three. The CT images were
      retrospectively reviewed by two radiologists. RESULTS: A total of 27 patients
      participated in this study. The common CT findings included diffuse bladder wall
      thickening (88.9%), small bladder volume (66.7%) and perivesical inflammation
      (44.4%). Twelve patients (44.4%) were diagnosed with hydronephrosis, including
      three patients with unilateral hydronephrosis and nine with bilateral
      hydronephrosis. Of these patients, nine had ureteral wall thickening (33.3%) and
      two (7.4%) had ureterovesical junction involvement (ie, they had hydronephrosis
      but no ureteral wall thickening). One patient had a ureteral obstruction because
      of a ureter stone. The correlation between upper urinary tract involvement and
      grading of the interstitial cystitis was statistically non-significant (p=0.33).
      Four patients (14.8%) had a vesicovaginal fistula which could be detected in the
      excretory phase only. CONCLUSIONS: Upper urinary tract involvement is common in
      patients with KIU. CTU might aid evaluation of the extent of KIU and prompt
      adequate management.

PMID- 24443559
TI  - NS1' protein expression facilitates production of Japanese encephalitis virus in
      avian cells and embryonated chicken eggs.
AB  - Japanese encephalitis virus (JEV), which belongs to the genus Flavivirus of the
      family Flaviviridae, is a leading cause of meningo-encephalitis in Asian
      countries. The flavivirus non-structural protein 1 (NS1) plays a role in virus
      replication and in the elicitation of an immune response. The NS1' protein found
      among the members of the JEV subgroup is an extended form of NS1 and is generated
      by a -1 ribosomal frameshift. This protein is known to be involved in viral
      pathogenicity; however, its specific function is still unknown. Here, we describe
      an investigation of the molecular function of NS1' protein through the production
      of JEV NS1'-expressing and -non-expressing clones and their infection of avian
      and mammalian cells. Efficient NS1' protein expression was observed in avian
      cells and was found to facilitate JEV production in both avian cultured cells and
      embryonated chicken eggs. NS1' protein was observed to co-localize with NS5
      protein and resulted in increased viral RNA levels in avian cells. These findings
      clearly indicate that NS1' enhances the production of JEV in avian cells and may
      facilitate the amplification/maintenance role of birds in the virus transmission
      cycle in nature. 

PMID- 24443560
TI  - ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance,
      and insulin sensitivity.
AB  - Adipose tissue contains one of the largest reservoirs of cholesterol in the body.
      Adipocyte dysfunction in obesity is associated with intracellular cholesterol
      accumulation, and alterations in cholesterol homeostasis have been shown to alter
      glucose metabolism in cultured adipocytes. ABCA1 plays a major role in
      cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol
      homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose
      tissue function and glucose metabolism is unknown. Our aim was to determine the
      impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose
      metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in
      adipocytes (ABCA1(-ad/-ad)). When fed a high-fat, high-cholesterol diet, ABCA1(
      ad/-ad) mice showed increased cholesterol and triglyceride stores in adipose
      tissue, developed enlarged fat pads, and had increased body weight. Associated
      with these phenotypic changes, we observed significant changes in the expression
      of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1,
      glut-4, adiponectin, and leptin. ABCA1(-ad/-ad) mice also demonstrated impaired
      glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We
      conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body
      weight, and whole-body glucose homeostasis. 

PMID- 24443561
TI  - Follistatin promotes adipocyte differentiation, browning, and energy metabolism.
AB  - Follistatin (Fst) functions to bind and neutralize the activity of members of the
      transforming growth factor-beta superfamily. Fst has a well-established role in
      skeletal muscle, but we detected significant Fst expression levels in
      interscapular brown and subcutaneous white adipose tissue, and further
      investigated its role in adipocyte biology. Fst expression was induced during
      adipogenic differentiation of mouse brown preadipocytes and mouse embryonic
      fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In
      differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins
      including uncoupling protein 1, PR domain containing 16, and PPAR gamma
      coactivator-1alpha was attenuated, but could be rescued by treatment with
      recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in
      differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO
      groups, suggesting that Fst produced by adipocytes may act in a paracrine manner.
      Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic
      differentiation identified several genes implicated in lipid and energy
      metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst
      treatment significantly increases cellular respiration in Fst-deficient cells.
      Our results implicate a novel role of Fst in the induction of brown adipocyte
      character and regulation of energy metabolism. 

PMID- 24443562
TI  - The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that
      preferentially binds to Holliday junctions.
AB  - MutLgamma, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical
      role during meiotic homologous recombination. The meiotic function of Mlh3 is
      fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E,
      inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the
      processing of joint molecules to generate crossover recombination products.
      Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is
      available, mechanistic insights into its function have been lacking due to the
      unavailability of the recombinant protein complex. Here we expressed the yeast
      Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that
      recombinant MutLgamma is a nuclease that nicks double-stranded DNA. We
      demonstrate that MutLgamma binds DNA with a high affinity and shows a marked
      preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex
      and show that preferential binding to Holliday junctions is a conserved capacity
      of eukaryotic MutLgamma complexes. Specific DNA recognition has never been
      observed with any other eukaryotic MutL homologue. MutLgamma thus represents a
      new paradigm for the function of the eukaryotic MutL protein family. We provide
      insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3
      prefers to bind the open unstacked Holliday junction form. This further supports
      the model where MutLgamma is part of a complex acting on joint molecules to
      generate crossovers in meiosis. 

PMID- 24443563
TI  - Regulation of human MutYH DNA glycosylase by the E3 ubiquitin ligase mule.
AB  - Oxidation of DNA is a frequent and constantly occurring event. One of the best
      characterized oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxo-G). It
      instructs most DNA polymerases to preferentially insert an adenine (A) opposite 8
      oxo-G instead of the appropriate cytosine (C) thus showing miscoding potential.
      The MutY DNA glycosylase homologue (MutYH) recognizes A:8-oxo-G mispairs and
      removes the mispaired A giving way to the canonical base excision repair that
      ultimately restores undamaged guanine (G). Here we characterize for the first
      time in detail a posttranslational modification of the human MutYH DNA
      glycosylase. We show that MutYH is ubiquitinated in vitro and in vivo by the E3
      ligase Mule between amino acids 475 and 535. Mutation of five lysine residues in
      this region significantly stabilizes MutYH, suggesting that these are the target
      sites for ubiquitination. The endogenous MutYH protein levels depend on the
      amount of expressed Mule. Furthermore, MutYH and Mule physically interact. We
      found that a ubiquitination-deficient MutYH mutant shows enhanced binding to
      chromatin. The mutation frequency of the ovarian cancer cell line A2780, analyzed
      at the HPRT locus can be increased upon oxidative stress and depends on the MutYH
      levels that are regulated by Mule. This reflects the importance of tightly
      regulated MutYH levels in the cell. In summary our data show that ubiquitination
      is an important regulatory mechanism for the essential MutYH DNA glycosylase in
      human cells. 

PMID- 24443564
TI  - Three-dimensional NMR structure of Hen Egg Gallin (Chicken Ovodefensin) reveals a
      new variation of the beta-defensin fold.
AB  - Gallin is a 41-residue protein, first identified as a minor component of hen egg
      white and found to be antimicrobial against Escherichia coli. Gallin may
      participate in the protection of the embryo during its development in the egg.
      Its sequence is related to antimicrobial beta-defensin peptides. In the present
      study, gallin was chemically synthesized 1) to further investigate its
      antimicrobial spectrum and 2) to solve its three-dimensional NMR structure and
      thus gain insight into structure-function relationships, a prerequisite to
      understanding its mode(s) of action. Antibacterial assays confirmed that gallin
      was active against Escherichia coli, but no additional antibacterial activity was
      observed against the other Gram-positive or Gram-negative bacteria tested. The
      three-dimensional structure of gallin, which is the first ovodefensin structure
      to have been solved to date, displays a new five-stranded arrangement. The gallin
      three-dimensional fold contains the three-stranded antiparallel beta-sheet and
      the disulfide bridge array typical of vertebrate beta-defensins. Gallin can
      therefore be unambiguously classified as a beta-defensin. However, an additional
      short two-stranded beta-sheet reveals that gallin and presumably the other
      ovodefensins form a new structural subfamily of beta-defensins. Moreover, gallin
      and the other ovodefensins calculated by homology modeling exhibit atypical
      hydrophobic surface properties, compared with the already known vertebrate beta
      defensins. These specific structural features of gallin might be related to its
      restricted activity against E. coli and/or to other yet unknown functions. This
      work provides initial understanding of a critical sequence-structure-function
      relationship for the ovodefensin family. 

PMID- 24443565
TI  - Functional cross-talk between ras and rho pathways: a Ras-specific GTPase
      activating protein (p120RasGAP) competitively inhibits the RhoGAP activity of
      deleted in liver cancer (DLC) tumor suppressor by masking the catalytic arginine
      finger.
AB  - The three deleted in liver cancer genes (DLC1-3) encode Rho-specific GTPase
      activating proteins (RhoGAPs). Their expression is frequently silenced in a
      variety of cancers. The RhoGAP activity, which is required for full DLC-dependent
      tumor suppressor activity, can be inhibited by the Src homology 3 (SH3) domain of
      a Ras-specific GAP (p120RasGAP). Here, we comprehensively investigated the
      molecular mechanism underlying cross-talk between two distinct regulators of
      small GTP-binding proteins using structural and biochemical methods. We
      demonstrate that only the SH3 domain of p120 selectively inhibits the RhoGAP
      activity of all three DLC isoforms as compared with a large set of other
      representative SH3 or RhoGAP proteins. Structural and mutational analyses provide
      new insights into a putative interaction mode of the p120 SH3 domain with the
      DLC1 RhoGAP domain that is atypical and does not follow the classical PXXP
      directed interaction. Hence, p120 associates with the DLC1 RhoGAP domain by
      targeting the catalytic arginine finger and thus by competitively and very
      potently inhibiting RhoGAP activity. The novel findings of this study shed light
      on the molecular mechanisms underlying the DLC inhibitory effects of p120 and
      suggest a functional cross-talk between Ras and Rho proteins at the level of
      regulatory proteins. 

PMID- 24443566
TI  - Cryo-electron microscopic structure of SecA protein bound to the 70S ribosome.
AB  - SecA is an ATP-dependent molecular motor pumping secretory and outer membrane
      proteins across the cytoplasmic membrane in bacteria. SecA associates with the
      protein-conducting channel, the heterotrimeric SecYEG complex, in a so-called
      posttranslational manner. A recent study further showed binding of a monomeric
      state of SecA to the ribosome. However, the true oligomeric state of SecA remains
      controversial because SecA can also form functional dimers, and high-resolution
      crystal structures exist for both the monomer and the dimer. Here we present the
      cryo-electron microscopy structures of Escherichia coli SecA bound to the
      ribosome. We show that not only a monomeric SecA binds to the ribosome but also
      that two copies of SecA can be observed that form an elongated dimer. Two copies
      of SecA completely surround the tunnel exit, providing a unique environment to
      the nascent polypeptides emerging from the ribosome. We identified the N-terminal
      helix of SecA required for a stable association with the ribosome. The structures
      indicate a possible function of the dimeric form of SecA at the ribosome. 

PMID- 24443567
TI  - Coagulation factor XIIIa substrates in human plasma: identification and
      incorporation into the clot.
AB  - Coagulation factor XIII (FXIII) is a transglutaminase with a well defined role in
      the final stages of blood coagulation. Active FXIII (FXIIIa) catalyzes the
      formation of epsilon-(gamma-glutamyl)lysine isopeptide bonds between specific Gln
      and Lys residues. The primary physiological outcome of this catalytic activity is
      stabilization of the fibrin clot during coagulation. The stabilization is
      achieved through the introduction of cross-links between fibrin monomers and
      through cross-linking of proteins with anti-fibrinolytic activity to fibrin.
      FXIIIa additionally cross-links several proteins with other functionalities to
      the clot. Cross-linking of proteins to the clot is generally believed to modify
      clot characteristics such as proteolytic susceptibility and hereby affect the
      outcome of tissue damage. In the present study, we use a proteomic approach in
      combination with transglutaminase-specific labeling to identify FXIIIa plasma
      protein substrates and their reactive residues. The results revealed a total of
      147 FXIIIa substrates, of which 132 have not previously been described. We
      confirm that 48 of the FXIIIa substrates were indeed incorporated into the
      insoluble fibrin clot during the coagulation of plasma. The identified substrates
      are involved in, among other activities, complement activation, coagulation,
      inflammatory and immune responses, and extracellular matrix organization. 

PMID- 24443568
TI  - Molecular determinants of allosteric modulation at the M1 muscarinic
      acetylcholine receptor.
AB  - Benzylquinolone carboxylic acid (BQCA) is an unprecedented example of a selective
      positive allosteric modulator of acetylcholine at the M1 muscarinic acetylcholine
      receptor (mAChR). To probe the structural basis underlying its selectivity, we
      utilized site-directed mutagenesis, analytical modeling, and molecular dynamics
      to delineate regions of the M1 mAChR that govern modulator binding and
      transmission of cooperativity. We identified Tyr-85(2.64) in transmembrane domain
      2 (TMII), Tyr-179 and Phe-182 in the second extracellular loop (ECL2), and Glu
      397(7.32) and Trp-400(7.35) in TMVII as residues that contribute to the BQCA
      binding pocket at the M1 mAChR, as well as to the transmission of cooperativity
      with the orthosteric agonist carbachol. As such, the BQCA binding pocket
      partially overlaps with the previously described "common" allosteric site in the
      extracellular vestibule of the M1 mAChR, suggesting that its high subtype
      selectivity derives from either additional contacts outside this region or
      through a subtype-specific cooperativity mechanism. Mutation of amino acid
      residues that form the orthosteric binding pocket caused a loss of carbachol
      response that could be rescued by BQCA. Two of these residues (Leu-102(3.29) and
      Asp-105(3.32)) were also identified as indirect contributors to the binding
      affinity of the modulator. This new insight into the structural basis of binding
      and function of BQCA can guide the design of new allosteric ligands with tailored
      pharmacological properties. 

PMID- 24443569
TI  - The different inhibition mechanisms of OXA-1 and OXA-24 beta-lactamases are
      determined by the stability of active site carboxylated lysine.
AB  - The catalytic efficiency of class D beta-lactamases depends critically on an
      unusual carboxylated lysine as the general base residue for both the acylation
      and deacylation steps of the enzyme. Microbiological and biochemical studies on
      the class D beta-lactamases OXA-1 and OXA-24 showed that the two enzymes behave
      differently when reacting with two 6-methylidene penems (penem 1 and penem 3):
      the penems are good inhibitors of OXA-1 but act more like substrates for OXA-24.
      UV difference and Raman spectroscopy revealed that the respective reaction
      mechanisms are different. The penems form an unusual intermediate, a 1,4
      thiazepine derivative in OXA-1, and undergo deacylation followed by the
      decarboxylation of Lys-70, rendering OXA-1 inactive. This inactivation could not
      be reversed by the addition of 100 mM NaHCO3. In OXA-24, under mild conditions
      (enzyme:inhibitor = 1:4), only hydrolyzed products were detected, and the enzyme
      remained active. However, under harsh conditions (enzyme:inhibitor = 1:2000), OXA
      24 was inhibited via decarboxylation of Lys-84; however, the enzyme could be
      reactivated by the addition of 100 mM NaHCO3. We conclude that OXA-24 not only
      decarboxylates with difficulty but also recarboxylates with ease; in contrast,
      OXA-1 decarboxylates easily but recarboxylates with difficulty. Structural
      analysis of the active site indicates that a crystallographic water molecule may
      play an important role in carboxylation in OXA-24 (an analogous water molecule is
      not found in OXA-1), supporting the suggestion that a water molecule in the
      active site of OXA-24 can lower the energy barrier for carboxylation
      significantly.

PMID- 24443571
TI  - Hypomania and bipolar II disorder -- diagnostic validity and clinical utility.

PMID- 24443570
TI  - The PSO4 protein complex associates with replication protein A (RPA) and
      modulates the activation of ataxia telangiectasia-mutated and Rad3-related (ATR).
AB  - The PSO4 core complex is composed of PSO4/PRP19/SNEV, CDC5L, PLRG1, and
      BCAS2/SPF27. Besides its well defined functions in pre-mRNA splicing, the PSO4
      complex has been shown recently to participate in the DNA damage response.
      However, the specific role for the PSO4 complex in the DNA damage response
      pathways is still not clear. Here we show that both the BCAS2 and PSO4 subunits
      of the PSO4 complex directly interact and colocalize with replication protein A
      (RPA). Depletion of BCAS2 or PSO4 impairs the recruitment of ATR-interacting
      protein (ATRIP) to DNA damage sites and compromises CHK1 activation and RPA2
      phosphorylation. Moreover, we demonstrate that both the RPA1-binding ability of
      BCAS2 and the E3 ligase activity of PSO4 are required for efficient accumulation
      of ATRIP at DNA damage sites and the subsequent CHK1 activation and RPA2
      phosphorylation. Our results suggest that the PSO4 complex functionally interacts
      with RPA and plays an important role in the DNA damage response. 

PMID- 24443572
TI  - [E. M. Jellinek's silenced and silencing transgenerational story].
AB  - Jellinek is a kind of archetypal character for future generations in the field of
      addiction studies. His implosion in the arena of alcoholism around the age of 50
      was an unexpected challenge to medical science. We know very little about his own
      role models giving an intellectual and moral compass to his pragmatic creativity.
      More than 30 years has passed since Jellinek's death when an American sociologist
      Ron Roizen started unearthing his silent story. Roizen discerned that there are a
      lot of unsaid and muted issues in his personal Hungarian past. Our paper, based
      on the authors' research in Hungarian archives and other sources reveals that not
      just Jellinek's personal but his transgenerational narrative has been not-yet
      said. This silenced and silencing history appears an unfinished business of
      acculturation of the family, which started prior to four generations. Authors
      have been concluding that the issue of religious conversion is a critical point
      in the process of acculturation. They examine the counter move of loyalty to
      family values and driving force of assimilation making their story unspeakable. 

PMID- 24443573
TI  - [Hungarian version of the Montreal Cognitive Assessment (MoCA) for screening mild
      cognitive impairment].
AB  - Mild cognitive impairment (MCI) can be considered as an intermediate stage
      between normal cognitive aging and dementia. Its screening is extremely important
      because within a year in 15-20% of cases dementia can evolve. In Hungary, the
      most widely used screening tool for both dementia and MCI is the Mini Mental
      State Examination (MMSE), which is often criticized for its poor screening
      sensitivity of mild dementia and MCI. To eliminate this problem, the Montreal
      Cognitive Assessment (MoCA) was developed, especially for screening MCI. Our
      study presents the first results with the Hungarian translation of MoCA. We used
      Beck Depression Inventory (BDI) for controlling depression. In MoCA the cutoff
      score between healthy and MCI persons was 24 out of 30. MoCA was more sensitive
      in detecting MCI than MMSE and its inner consistency was also slightly higher.
      Specificity of the tests to detect MCI was similar. The results on BDI were not
      related to either MoCA or MMSE. Our results suggest that MoCA can be a useful
      tool to detect cognitive decline. 

PMID- 24443574
TI  - [Family malediction in the background of panic disorder -- case report].
AB  - The author reports the combined treatment with pharmacotherapy and psychotherapy
      of a patient suffering from recurrent panic disorder. Respected the patient's
      subjective aspects, at the beginning there was only supportive therapy
      supplemented with autogenic training. At this time the treatment was aimed at
      anxiety reducing directly. Later, when the panic disorder returned, the therapy
      was completed with shorter periods of cognitive behavioral therapy. During these
      sessions the patient learned that the underlying, hidden causes of her mental
      disorders could be revealed, understood and coped with, thereby more permanent
      periods without symptoms could be achieved. During the last sessions of the
      treatment the patient herself recognised the main cause of her recurrent panic
      disorder: it was a sentence she was told by her relatives when she was 18, which
      acted as a malediction-sentence. After the identification and modification of the
      dysfunctional attitudes and basic assumptions related to the malediction-sentence
      the patient had no panic symptoms anymore and she gradually stopped taking her
      medication. This case report demonstrates that the underlying, deep-rooted
      psychic cause of panic disorder can be revealed and understood and by this way
      permanent asymptomatic state can be achieved. This case also strengthens the
      common knowledge that panic disorder can be treated most successfully if
      pharmacotherapy is combined with psychotherapy. 

PMID- 24443575
TI  - [Prospective study of children's perceptions of parental behavior: psychometric
      properties of the Hungarian version of the EMBU-C questionnaire].
AB  - BACKGROUND: Preliminary research findings show that the parental rearing
      behaviour has a basic effect on the psychosocial development of the child,
      moreover, the inadequate parenting is related to some psychopathology occurring
      in childhood and adulthood. One reason in the development of this research
      subject was the appearance of the questionnaires, which judge the quality of the
      parenting and its effects by the children's recollections. Recently, there are
      new prospective instruments to remove the memory biases. The aim of this study
      was to standardize on a Hungarian sample one of these instruments, EMBU-C, made
      for primary school aged children. METHODS: Primary school aged children (7-12
      year old) were examined (n=108). Beyond demographic data the item base of the
      EMBU-C and the STAIC inventory were filled up. RESULTS: It was demonstrated the
      four factor structure of the EMBU-C (the names of the factors are respectively:
      Emotional warmth, Rejection, Overprotection and Favouring subject). The internal
      consistency of the inventory was in accordance with the international data. The
      concurrent validity also was proved by the STAIC. The recorded data are in
      accordance to the adolescent and adult versions of the EMBU. The most important
      result is that the parental rejection and overprotection may be related to the
      children's anxiety symptoms. Another important result is that the primary school
      aged children are disposed to interpret the intrusion component of the parental
      overprotection as emotional warmth that differs from adolescent and adult
      results. CONCLUSIONS: The successful standardization of the EMBU-C in Hungarian
      sample has positive consequences both to the clinical work and the research
      attempts, because it allows the investigation of the parental correlates of
      childhood psychopathologies, as well as the comparison of the results between
      different cohorts and international samples.

PMID- 24443576
TI  - [Unemployment as psychological stress and coping methods].
AB  - The present article focuses on unemployment as a stressor and a crisis situation
      as well. Both the definition and theories about this phenomenon are analyzed. The
      author tries to explore unemployment like a stressor and a special crisis
      situation afterwards illustrating it by several Hungarian results of the
      unemployment research. The author tries to emphasize coping methods of
      personality. Last but not least unemployment is presented like a special problem
      that could be solved by some practical aspects recommended for the professionals.

PMID- 24443577
TI  - [Clinical characteristics of 5 hospitalized 3,4-methylenedioxypyrovalerone (MDPV)
      users].
AB  - A new illegal psychotropic substance appeared in Hungary during the first months
      of 2011. Acutely hospitalized patients with psychosis disclosed using a new type
      of designer drug, previously unknown to clinicians. As the new drug became better
      known, the cases with acute intoxication were often also transported to
      toxicology departments. In this study we summarize 5 short case studies that
      demonstrate the heterogeneous symptoms associated with MDPV abuse, and draw
      attention to the frequently occurring delusions, and the extended risk of
      intravenous substance use. Present case studies include patients with and without
      psychiatric history, regular and occasional users, intravenous and other routes
      of administration. In the short run antipsychotic therapy reduced the symptoms in
      all cases, but there is no clear therapeutic guideline for the treatment of
      patients having psychiatric problems associated with these drugs at the present
      time. The laboratory examination is unresolved as well. Mephedrone, MDPV and
      recent drugs have drawn attention to the problem of designer drugs again. This
      article examines the interaction of drug consumption trends and changes in law,
      apropos of the presented cases. This information can be helpful for the future
      treatment of MDPV or other designer drug users. Possible research and therapeutic
      implications are also discussed. 

PMID- 24443578
TI  - [Narcissism in the world of Facebook. An evolutionary psychopathological
      interpretation].
AB  - In the last few decades there has been a considerable increase in the levels of
      narcissism among the population of individualistic, western cultures. The
      phenomena of narcissism induced a large number of psychological researches, some
      of which approaches the issue from changes in environmental factors. The modern
      environment of these days is substantially different from the one to which our
      ancestors have adapted over millions of years of evolution. The research results
      of narcissism from the perspective of evolutionary psychopathology approach have
      yet to integrate.The present review focuses on two studies and empirical findings
      induced by them in which an attempt is made to explore the evolutionary origins
      of narcissism. Relating to these studies we present the main mechanisms by which
      evolution may have played a role in the development and maintenance of
      narcissism. One of the significant elements of the current, changing social
      environment allowing virtual contacts is the social networking site called
      Facebook. Following the presentation of the main features of the site we discuss
      research results in connection with narcissistic traits and Facebook usage.
      Finally an attempt is made to integrate these findings into an evolutionary
      psychopathological framework. 

PMID- 24443579
TI  - [Therapy helps -- psychosocial support for patients diagnosed with breast cancer,
      reducing anxiety and depression].
AB  - The results of epidemiological researches are alarming. It is anticipated that in
      the next few decades the number of patients suffering from malignant tumours will
      double. Caring for patients with cancer sets a serious challenge to the health
      services - not only to the oncology specialists, but among the others also to the
      psychiatrists and the psychologists. The diagnosis of cancer commonly pushes the
      patient into a depressed, hopeless and anxious emotional state that can persist
      for years after the diagnosis causing serious damage - a decline in the health
      related quality of life, it narrows life opportunities, it makes coping and
      cooperating more difficult, and it predicts the progression of the disease and
      mortality. Treating these is crucial. Results published in related literature
      prove the positive effects of psychosocial interventions (a wide range of
      psychological and psychosocial support of the patients) on emotional distress.
      The most commonly applied interventions are the supportive-expressive therapies
      and cognitive methods. Recently a new trend started unfolding where the patients,
      as their complementary care instead of having single interventions they are
      offered complex programmes - psychotherapy, exercise, diet, education, etc. are
      all applied together, amplifying the synergic effects of the components. Our
      research is aimed to assess the results of a complex programme in decreasing
      emotional distress in women diagnosed with primer breast cancer (n=173,
      experimental group n=86, of whom 34 participated the programme, control group
      n=87) short term (at the end of the 15 week long programme) and longitudinally
      (15 months after the end of programme). The results are very promising: there
      were significant improvements in patients, a decrease in depression (Beck), as
      well as in anxiety (STAI), and some aspects of positive effects showed long
      lasting. 

PMID- 24443580
TI  - MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and
      prognostic insights.
AB  - The diagnosis of conventional and oncocytic poorly differentiated (oPD) thyroid
      carcinomas is difficult. The aim of this study is to characterise their largely
      unknown miRNA expression profile and to compare it with well-differentiated
      thyroid tumours, as well as to identify miRNAs which could potentially serve as
      diagnostic and prognostic markers. A total of 14 poorly differentiated (PD), 13
      oPD, 72 well-differentiated thyroid carcinomas and eight normal thyroid specimens
      were studied for the expression of 768 miRNAs using PCR-Microarrays. MiRNA
      expression was different between PD and oPD thyroid carcinomas, demonstrating
      individual clusters on the clustering analysis. Both tumour types showed
      upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p, and
      downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p
      and of miR-886-3p as compared with normal thyroid tissue. In addition, the oPD
      thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The
      difference in expression was also observed between miRNA expression in PD and
      well-differentiated tumours. The CHAID algorithm allowed the separation of PD
      from well-differentiated thyroid carcinomas with 73-79% accuracy using miR-23b
      and miR-150 as a separator. Kaplan-Meier and multivariate analysis showed a
      significant association with tumour relapses (for miR-23b) and with tumour
      specific death (for miR-150) in PD and oPD thyroid carcinomas. MiRNA expression
      is different in conventional and oPD thyroid carcinomas in comparison with well
      differentiated thyroid cancers and can be used for discrimination between these
      tumour types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the
      potential to be used in a clinical setting, delivering prognostic and diagnostic
      informations. 

PMID- 24443582
TI  - Effect of Na adsorption on the structural and electronic properties of Si(111)?3
      * ?3-Au surface.
AB  - Adsorption of ~0.1 ML of Na onto the Si(111)?3 * ?3-Au surface held at 300 
      degrees C has been found to induce pronounced changes in its structural and
      electronic properties. Domain wall networks, characteristic of the pristine
      surface, are removed completely, leading to the formation of a highly ordered
      homogeneous surface. The original atomic arrangement of the Si(111)?3 * ?3-Au is
      preserved and Na atoms occupy T4 adsorption sites at the centers of surface Si
      trimers. Upon Na adsorption, a pronounced metallic S1 surface-state band
      develops. It is characterized by a large spin splitting (momentum splitting at
      the Fermi level Deltak? = 0.027 A(-1) and consequent energy splitting DeltaEF =
      110 meV), large electron filling (on the order of 0.5 electrons per ?3 * ?3 unit
      cell) and small effective electron mass of (0.028 +/- 0.006)me. The natural
      consequence of the latter properties is a high surface conductivity of the
      Si(111)?3 * ?3-(Au, Na) surface.

PMID- 24443581
TI  - Targeting gamma-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.
AB  - gamma-herpesviruses (gammaHVs) are common human pathogens that encode homologs of
      the anti-apoptotic cellular Bcl-2 proteins, which are critical to viral
      reactivation and oncogenic transformation. The murine gammaHV68 provides a
      tractable in vivo model for understanding general features of these important
      human pathogens. Bcl-XL, a cellular Bcl-2 homolog, and the murine gammaHV68 Bcl-2
      homolog, M11, both bind to a BH3 domain within the key autophagy effector Beclin
      1 with comparable affinities, resulting in the down-regulation of Beclin 1
      mediated autophagy. Despite this similarity, differences in residues lining the
      binding site of M11 and Bcl-XL dictate varying affinities for the different BH3
      domain-containing proteins. Here we delineate Beclin 1 differential specificity
      determinants for binding to M11 or Bcl-XL by quantifying autophagy levels in
      cells expressing different Beclin 1 mutants and either M11 or Bcl-XL, and we show
      that a G120E/D121A Beclin 1 mutant selectively prevents down-regulation of Beclin
      1-mediated autophagy by Bcl-XL, but not by M11. We use isothermal titration
      calorimetry to identify a Beclin 1 BH3 domain-derived peptide that selectively
      binds to M11, but not to Bcl-XL. The x-ray crystal structure of this peptide
      bound to M11 reveals the mechanism by which the M11 BH3 domain-binding groove
      accommodates this M11-specific peptide. This information was used to develop a
      cell-permeable peptide inhibitor that selectively inhibits M11-mediated, but not
      Bcl-XL-mediated, down-regulation of autophagy. 

PMID- 24443583
TI  - Simulation modelling and resource allocation in complex services.

PMID- 24443584
TI  - The Cystic Fibrosis Foundation Patient Registry as a tool for use in quality
      improvement.

PMID- 24443586
TI  - Dimensions of Rural-to-Urban Migration and Premarital Pregnancy in Kenya.
AB  - Rural-to urban migration is increasingly common among youth and could affect
      sexual activities. We use life history calendar data collected in Kisumu, Kenya,
      to investigate how the timing and number of rural-to-urban moves are associated
      with premarital pregnancy. Among sexually experienced young women aged 18-24
      (N=226), 39 percent have experienced a premarital pregnancy and 60 percent
      experienced a move in the last 10 years. Results of the event history analysis
      show that those who experienced one or two moves or whose most recent move
      occurred in the last seven to 12 months are at increased risk of premarital
      pregnancy compared to nonmovers. Those whose last move occurred at age 13 or
      younger were also at an elevated risk. Migration brings about specific needs for
      youth, including the need for sexual and reproductive health education and
      services, which should be made available and accessible to new urban residents.

PMID- 24443585
TI  - Structure and biochemical properties of the alkene producing cytochrome P450
      OleTJE (CYP152L1) from the Jeotgalicoccus sp. 8456 bacterium.
AB  - The production of hydrocarbons in nature has been documented for only a limited
      set of organisms, with many of the molecular components underpinning these
      processes only recently identified. There is an obvious scope for application of
      these catalysts and engineered variants thereof in the future production of
      biofuels. Here we present biochemical characterization and crystal structures of
      a cytochrome P450 fatty acid peroxygenase: the terminal alkene forming OleTJE
      (CYP152L1) from Jeotgalicoccus sp. 8456. OleTJE is stabilized at high ionic
      strength, but aggregation and precipitation of OleTJE in low salt buffer can be
      turned to advantage for purification, because resolubilized OleTJE is fully
      active and extensively dissociated from lipids. OleTJE binds avidly to a range of
      long chain fatty acids, and structures of both ligand-free and arachidic acid
      bound OleTJE reveal that the P450 active site is preformed for fatty acid
      binding. OleTJE heme iron has an unusually positive redox potential (-103 mV
      versus normal hydrogen electrode), which is not significantly affected by
      substrate binding, despite extensive conversion of the heme iron to a high spin
      ferric state. Terminal alkenes are produced from a range of saturated fatty acids
      (C12-C20), and stopped-flow spectroscopy indicates a rapid reaction between
      peroxide and fatty acid-bound OleTJE (167 s(-1) at 200 MUm H2O2). Surprisingly,
      the active site is highly similar in structure to the related P450BSbeta, which
      catalyzes hydroxylation of fatty acids as opposed to decarboxylation. Our data
      provide new insights into structural and mechanistic properties of a robust P450
      with potential industrial applications. 

PMID- 24443587
TI  - Kernel Smoothed Profile Likelihood Estimation in the Accelerated Failure Time
      Frailty Model for Clustered Survival Data.
AB  - Clustered survival data frequently arise in biomedical applications, where event
      times of interest are clustered into groups such as families. In this article we
      consider an accelerated failure time frailty model for clustered survival data
      and develop nonparametric maximum likelihood estimation for it via a kernel
      smoother aided EM algorithm. We show that the proposed estimator for the
      regression coefficients is consistent, asymptotically normal and semiparametric
      efficient when the kernel bandwidth is properly chosen. An EM-aided numerical
      differentiation method is derived for estimating its variance. Simulation studies
      evaluate the finite sample performance of the estimator, and it is applied to the
      Diabetic Retinopathy data set.

PMID- 24443588
TI  - The Use of High Performance Liquid Chromatography to Speciate and Characterize
      the Epidemiology of Mycobacteria.
AB  - OBJECTIVE: We evaluated high-performance liquid chromatography (HPLC) for species
      identification of mycobacteria from various clinical specimens in an urban
      hospital in South Korea between January 2005 and December 2009. METHODS: In the
      study period 24,774 cultures were completed, yielding the 3215 clinical isolates
      cultivated for mycobacteria and positive cultures that had mycolic acid
      investigated by HPLC. For species identification, we compared HPLC patterns of
      clinical isolates with 33 standard Mycobacterium species. RESULTS: There were 3
      different HPLC groups with single, double, and triple-cluster patterns
      representing 9, 20, and 4 mycobacterial species, respectively. Species
      identification rates of HPLC for Mycobacterium tuberculosis and nontuberculous
      mycobacteria (NTM) were found to be 100% and 95.6%, respectively. Among
      mycobacterial isolates, 12.1% were NTM-positive. There were 20 different NTM
      species with frequencies of 0.3%~15.5%. CONCLUSION: The HPLC method was highly
      sensitive identifying NTM isolated from clinical specimens.

PMID- 24443589
TI  - The Consequences of Teenage Childbearing: Consistent Estimates When Abortion
      Makes Miscarriage Nonrandom.
AB  - Miscarriage, even if biologically random, is not socially random. Willingness to
      abort reduces miscarriage risk. Because abortions are favorably selected among
      pregnant teens, those miscarrying are less favorably selected than those giving
      birth or aborting but more favorably selected than those giving birth. Therefore,
      using miscarriage as an instrument is biased towards a benign view of teen
      motherhood while OLS on just those giving birth or miscarrying has the opposite
      bias. We derive a consistent estimator that reduces to a weighted average of OLS
      and IV when outcomes are independent of abortion timing. Estimated effects are
      generally adverse but modest.

PMID- 24443590
TI  - Electrocatalytic oxidation of small organic molecules in acid medium: enhancement
      of activity of noble metal nanoparticles and their alloys by supporting or
      modifying them with metal oxides.
AB  - Different approaches to enhancement of electrocatalytic activity of noble metal
      nanoparticles during oxidation of small organic molecules (namely potential fuels
      for low-temperature fuel cells such as methanol, ethanol and formic acid) are
      described. A physical approach to the increase of activity of catalytic
      nanoparticles (e.g. platinum or palladium) involves nanostructuring to obtain
      highly dispersed systems of high surface area. Recently, the feasibility of
      enhancing activity of noble metal systems through the formation of bimetallic
      (e.g. PtRu, PtSn, and PdAu) or even more complex (e.g. PtRuW, PtRuSn) alloys has
      been demonstrated. In addition to possible changes in the electronic properties
      of alloys, specific interactions between metals as well as chemical reactivity of
      the added components have been postulated. We address and emphasize here the
      possibility of utilization of noble metal and alloyed nanoparticles supported on
      robust but reactive high surface area metal oxides (e.g. WO3, MoO3, TiO2, ZrO2,
      V2O5, and CeO2) in oxidative electrocatalysis. This paper concerns the way in
      which certain inorganic oxides and oxo species can act effectively as supports
      for noble metal nanoparticles or their alloys during electrocatalytic oxidation
      of hydrogen and representative organic fuels. Among important issues are possible
      changes in the morphology and dispersion, as well as specific interactions
      leading to the improved chemisorptive and catalytic properties in addition to the
      feasibility of long time operation of the discussed systems.

PMID- 24443591
TI  - Moral Selves and Moral Scenes: Narrative Experiments in Everyday Life.

PMID- 24443592
TI  - Response organization in selective adaptation to speech sounds.
AB  - Previous experiments in speech perception using the selective adaptation
      procedure have found a shift in the locus of the category boundary for a series
      of speech stimuli following repeated exposure to an adapting syllable. The locus
      of the boundary moves toward the category of the adapting syllable. Most
      investigators have interpreted these findings in terms of feature detector models
      in which specific detectors are reduced in sensitivity through repeated
      adaptation. The present experiment was conducted to determine whether the
      adaptation results might be due to changes in response organization as a
      consequence of the labeling instructions presented to subjects in selective
      adaptation experiments. A perceptually ambiguous speech stimulus was selected
      from the middle of a [bi]-[di] test series and used as an adaptor under two
      different sets of instructions. One group of subjects was told that the adapting
      stimulus was the syllable [bi], while another group was told that the stimulus
      was the syllable [di]. The acoustically ambiguous adaptor failed to produce a
      shift in the locus of the category boundary in the direction predicted on the
      basis of the labeling instructions presented to subjects. These results indicate
      that the acoustic attributes and perceived quality of the adapting stimulus
      determine the direction and magnitude of the adaptation effects rather than the
      labels provided by the experimenter.

PMID- 24443594
TI  - A Life Course Perspective on Child Health, Academic Experiences and Occupational
      Skill Qualifications in Adulthood: Evidence from a British Cohort.
AB  - Existing research rarely examines the social consequences of poor childhood
      health from a longitudinal perspective. Using data from the British National
      Child Development Study, I follow a cohort from before birth through middle age
      to examine whether children's health limitations before and during the
      educational process predict occupational skill qualifications in mid-adulthood,
      and whether any negative consequences are strongest for children in persistently
      poor health. I also examine whether differences in achievement explain the
      observed associations, and at what point during the schooling process performance
      begins to play a large explanatory role. Poor health is strongly negatively
      related to qualifications in adulthood, particularly for children in persistently
      poor health. These associations are largely explained by differences in
      performance early in children's academic careers, before the first important
      transition point. The relationship between prenatal maternal smoking and mid
      adulthood qualifications is more persistent. This paper demonstrates that a
      static conceptualization of childhood health is inadequate to fully understand
      the dynamic process through which social status and health over the course of
      childhood have long-run consequences for the adult life course.

PMID- 24443593
TI  - Fabrication of Cell Patches Using Biodegradable Scaffolds with a Hexagonal Array
      of Interconnected Pores (SHAIPs).
AB  - Cell patches are widely used for healing injuries on the surfaces or interfaces
      of tissues such as those of epidermis and myocardium. Here we report a novel type
      of porous scaffolds made of poly(D,L-lactic-co-glycolic acid) for fabricating
      cell patches. The scaffolds have a single layer of spherical pores arranged in a
      unique hexagonal pattern and are therefore referred to as "scaffolds with a
      hexagonal array of interconnected pores (SHAIPs)". SHAIPs contain both uniform
      pores and interconnecting windows that can facilitate the exchange of
      biomacromolecules, ensure homogeneous cell seeding, and promote cell migration.
      As a proof-of-concept demonstration, we have created skeletal muscle patches with
      a thickness of approximately 150 MUm using SHAIPs. The myoblasts seeded in the
      scaffolds maintained high viability and were able to differentiate into multi
      nucleated myotubes. Moreover, neovasculature could efficiently develop into the
      patches upon subcutaneous implantation in vivo.

PMID- 24443601
TI  - Transforming nursing home culture: evidence for practice and policy.
AB  - The nursing home culture change movement aims to improve resident quality of life
      and quality of care by emphasizing the deinstitutionalization of nursing home
      culture and focusing on person-centered care. This article briefly reviews the
      history of culture change, discusses some of the challenges related to culture
      change in nursing homes, and overviews the conceptualization and select models of
      culture change. Building from this background, it critiques current
      understanding, identifies critical research questions, and notes key issues
      arising during a workshop that addressed existing and emerging evidence in the
      field. This review and analysis provide a context for how 9 accompanying papers
      in this supplemental issue of The Gerontologist fill identified evidence gaps and
      provide evidence for future practice and policies that aim to transform nursing
      home culture. 

PMID- 24443602
TI  - A "recipe" for culture change? Findings from the THRIVE survey of culture change
      adopters.
AB  - PURPOSE OF THE STUDY: Descriptions of culture change adoption are often complex
      and varied, creating a challenge for those seeking guidance about which of the
      many components of culture change to adopt and in what order and combination.
      DESIGN AND METHODS: To begin to address this question, members of The Research
      Initiative Valuing Eldercare (THRIVE) developed and distributed an online survey
      to 327 known culture change adopters. Of these, 164 (50%) completed the survey.
      Data were analyzed to identify adopted components, co-occurrence of adopted
      components, and differences in these across various types of nursing home models
      (i.e., traditional unit, household, and small house). RESULTS: Our findings
      support unique co-occurrence of components across nursing home models. Results
      also show that homes with more traditional environments have been able to
      implement certain culture change components without large capital investments
      required by renovations. IMPLICATIONS: The adoption patterns suggest that the co
      occurrence of components should be considered when pursuing organizational
      transformations to support culture change.

PMID- 24443603
TI  - Changing the culture of mouth care: mouth care without a battle.
AB  - PURPOSE OF THE STUDY: Culture change aims to fundamentally improve care provision
      in a manner consistent with individual preferences. However, few studies of
      culture change have focused on the quality of daily care, despite the fact that
      system-wide efforts are important to assure the effectiveness, adoption, and
      sustainability of person-centered care to meet daily needs. This paper describes
      a new culture change practice, Mouth Care Without a Battle. The focus on mouth
      care is predicated on the important association between person-centered support
      for oral hygiene and quality of life. DESIGN AND METHODS: Mouth Care Without a
      Battle is a person-centered approach to quality mouth care for persons with
      cognitive and physical impairment. It was developed by an interdisciplinary team
      of clinician researchers based on literature review, consultation with experts,
      environmental scan of existing programs, and testing in nursing homes. Building
      from the success of Bathing Without a Battle, Mouth Care Without a Battle was
      evaluated in terms of changed care practices and outcomes, developed into a
      training program, and packaged for dissemination as a digital video disk (DVD)
      and website. RESULTS: The development and evaluation of Mouth Care Without a
      Battle demonstrate attention to the areas necessary to establish the evidence
      base for culture change, to ultimately empower and support staff to provide care
      to achieve quality outcomes. IMPLICATIONS: As illustrated in this paper, it is
      beneficial to build the evidence base for culture change by attending to care
      processes and outcomes benefiting all residents, ability to implement culture
      change, and costs of implementation.

PMID- 24443604
TI  - Culture change and nursing home quality of care.
AB  - PURPOSE OF THE STUDY: Culture change models are intended to improve the quality
      of life for nursing home residents, but the impact of these models on quality of
      care is unknown. We evaluated the impact of the implementation of nursing home
      culture change on the quality of care, as measured by staffing, health-related
      survey deficiencies, and Minimum Data Set (MDS) quality indicators. DESIGN AND
      METHODS: From the Pioneer Network, we have data on whether facilities were
      identified by experts as "culture change" providers in 2004 and 2009. Using
      administrative data, we employed a panel-based regression approach in which we
      compared pre-post quality outcomes in facilities adopting culture change between
      2004 and 2009 against pre-post quality outcomes for a propensity score-matched
      comparison group of nonadopters. RESULTS: Nursing homes that were identified as
      culture change adopters exhibited a 14.6% decrease in health-related survey
      deficiency citations relative to comparable nonadopting homes, while experiencing
      no significant change in nurse staffing or various MDS quality indicators.
      IMPLICATIONS: This research represents the first large-scale longitudinal
      evaluation of the association of culture change and nursing home quality of care.
      Based on the survey deficiency results, nursing homes that were identified as
      culture change adopters were associated with better care although the surveyors
      were not blind to the nursing home's culture change efforts. This finding
      suggests culture change may have the potential to improve MDS-based quality
      outcomes, but this has not yet been observed.

PMID- 24443605
TI  - High-performance workplace practices in nursing homes: an economic perspective.
AB  - To develop implications for research, practice and policy, selected economics and
      human resources management research literature was reviewed to compare and
      contrast nursing home culture change work practices with high-performance human
      resource management systems in other industries. The organization of nursing home
      work under culture change has much in common with high-performance work systems,
      which are characterized by increased autonomy for front-line workers, self
      managed teams, flattened supervisory hierarchy, and the aspiration that workers
      use specific knowledge gained on the job to enhance quality and customization.
      However, successful high-performance work systems also entail intensive
      recruitment, screening, and on-going training of workers, and compensation that
      supports selective hiring and worker commitment; these features are not usual in
      the nursing home sector. Thus despite many parallels with high-performance work
      systems, culture change work systems are missing essential elements: those that
      require higher compensation. If purchasers, including public payers, were willing
      to pay for customized, resident-centered care, productivity gains could be shared
      with workers, and the nursing home sector could move from a low-road to a high
      road employment system. 

PMID- 24443606
TI  - Developing the green house nursing care team: variations on development and
      implementation.
AB  - PURPOSE OF THE STUDY: A core component of the Green House nursing home model is
      an altered supervisory relationship between the nurse and direct care workers.
      Some have expressed concern that the Green House model might weaken professional
      nursing oversight, threatening the quality of clinical care. This qualitative
      research study explores the role of the nurse as implemented in the Green House
      model, focusing on how variations in the nursing team influence clinical care
      practices. DESIGN AND METHODS: Dimensional analysis, a "second generation"
      grounded theory methodology, was used to conduct this study. Data were collected
      through observations and interviews with 37 nurses, 68 CNAs, and 11 Guides
      working at 11 Green House sites. RESULTS: Implementation of the nursing role
      within the Green House model varied both within and across sites. Four nursing
      model types were identified: Traditional, Visitor, Parallel, and Integrated. Care
      processes, CNA/Shahbaz skill development, and worker stress varied with each
      nursing model. IMPLICATIONS: Government policies have been enacted to support
      culture change. However, there is currently little guidance for regulators,
      providers, or consumers regarding variability in how culture change practices are
      implemented and consequences of these variations. This article outlines the
      importance of understanding these practices at a level of detail that
      distinguishes and supports those that are most promising.

PMID- 24443607
TI  - What does the evidence really say about culture change in nursing homes?
AB  - PURPOSE OF THE STUDY: Although nursing home culture change efforts are becoming
      more widespread, there have been few efforts to systematically compile the
      evidence related to the efficacy of culture change. This study uses an analytic
      framework to evaluate the existing evidence for the impact of culture change on
      nursing home quality. We focus on the nature and scope of culture change
      interventions, measurement of culture change and adherence to interventions,
      measurement of culture change outcomes, and the relationship between culture
      change and its outcomes. DESIGN AND METHODS: We conducted a comprehensive review
      of peer-reviewed and gray literature published between 2005 and 2012 to identify
      intervention evaluations that addressed at least one culture change domain. Of
      4,982 identified publications, 625 underwent full review; 27 peer-reviewed and 9
      gray literature studies met inclusion criteria. RESULTS: Studies varied widely in
      scope and outcomes. Most addressed more than one culture change domain; resident
      direction, home environment, and close relationships were most common. Few
      studies measured culture change implementation, but most used validated tools to
      measure outcomes. Although few studies reported negative outcomes, there was
      little consistent evidence of positive effects. IMPLICATIONS: Nursing home
      culture change remains an evolving field. Although culture change has clear face
      validity, the current evidence does not give providers sufficient information for
      selecting interventions based on the expectation of improving outcomes. Rigorous
      research on implementation and outcomes of culture change is needed to determine
      the specific impact of culture change on quality and to provide guidance to
      providers and policy makers.

PMID- 24443608
TI  - Who are the innovators? Nursing homes implementing culture change.
AB  - PURPOSE OF THE STUDY: A key directive of the Affordable Care Act of 2010 is to
      transform both institutional and community-based long-term care into a more
      person-centered system. In the nursing home industry, the culture change movement
      is central to this shift in philosophy. If policymakers are to further encourage
      implementation of culture change, they need to better understand the factors
      associated with implementation. DESIGN AND METHODS: Using logistic regression (N
      = 16,835), we examined the extent to which resident, facility, and state
      characteristics relate to a nursing home being identified by experts as having
      implemented culture change over the period 2004 through 2011. RESULTS: At
      baseline, the 291 facilities that were later identified by experts to have
      implemented culture change were more often nonprofit-owned, larger in size, and
      had fewer Medicaid and Medicare residents. Implementers also had better baseline
      quality with fewer health-related survey deficiencies and greater licensed
      practical nurse and nurse aide staffing. States experienced greater culture
      change implementation when they paid a higher Medicaid per diem. IMPLICATIONS: To
      date, nursing home culture change has been implemented differentially by higher
      resource facilities, and nursing homes have been responsive to state policy
      factors when implementing culture change.

PMID- 24443609
TI  - Medicaid capital reimbursement policy and environmental artifacts of nursing home
      culture change.
AB  - PURPOSE OF THE STUDY: To examine how Medicaid capital reimbursement policy is
      associated with nursing homes (NHs) having high proportions of private rooms and
      small households. DESIGN AND METHODS: Through a 2009/2010 NH national survey, we
      identified NHs having small households and high proportions of private rooms
      (>=76%). A survey of state Medicaid officials and policy document review provided
      2009 policy data. Facility- and county-level covariates were from Online Survey,
      Certification and Reporting, the Area Resource File, and aggregated resident
      assessment data (minimum data set). The policy of interest was the presence of
      traditional versus fair rental capital reimbursement policy. Average Medicaid per
      diem rates and the presence of NH pay-for-performance (p4p) reimbursement were
      also examined. A total of 1,665 NHs in 40 states were included. Multivariate
      logistic regression analyses (with clustering on states) were used. RESULTS: In
      multivariate models, Medicaid capital reimbursement policy was not significantly
      associated with either outcome. However, there was a significantly greater
      likelihood of NHs having many private rooms when states had higher Medicaid rates
      (per $10 increment; adjusted odds ratio [AOR] 1.13; 95% CI 1.049, 1.228), and in
      states with versus without p4p (AOR 1.78; 95% CI 1.045, 3.036). Also, in states
      with p4p NHs had a greater likelihood of having small households (AOR 1.78; 95%
      CI 1.045, 3.0636). IMPLICATIONS: Higher NH Medicaid rates and reimbursement
      incentives may contribute to a higher presence of 2 important environmental
      artifacts of culture change-an abundance of private rooms and small households.
      However, longitudinal research examining policy change is needed to establish the
      cause and effect of the associations observed.

PMID- 24443610
TI  - Building a state coalition for nursing home excellence.
AB  - PURPOSE OF THE STUDY: This article describes the successful evolution of a state
      coalition for nursing home excellence that brought together organizations that
      had once worked in silos to improve the quality of care through the
      implementation of culture change for Arkansas' 240 nursing homes with 27,700
      residents. DESIGN AND METHODS: The Coalition was established in 2004 when
      stakeholders were invited to participate in a retreat to explore how they could
      come together with a common goal to improve the care of older Arkansans. These
      stakeholders were encouraged to bring their organization's perspectives to the
      Coalition and determine ways to work with others. The continuous refinement of
      the Coalition's activities involved revisiting goals of the Coalition, assessing
      the need for other stakeholders, identifying gaps and overlaps in quality and
      culture change programming, and providing feedback to Coalition members. RESULTS:
      The Coalition stakeholders had the leadership to articulate and mobilize others
      around a common vision of improving quality of care in nursing homes through
      culture change. Over time, the Coalition members developed a willingness to share
      resources and to speak as one voice. IMPLICATIONS: Stakeholders from diverse
      organizations and governing bodies can come together to complement each other's
      work and collaborate on programs to build a better system of care for the frail
      and elderly persons across a state. The success of this statewide effort lends
      support for policies that encourage regional coalitions of providers to improve
      care.

PMID- 24443611
TI  - Implications for policy: the nursing home as least restrictive setting.

PMID- 24443612
TI  - PREDICTING RECIDIVISM FOR RELEASED STATE PRISON OFFENDERS: Examining the
      Influence of Individual and Neighborhood Characteristics and Spatial Contagion on
      the Likelihood of Reincarceration.
AB  - We examined the influence of individual and neighborhood characteristics and
      spatial contagion in predicting reincarceration on a sample of 5,354 released
      Pennsylvania state prisoners. Independent variables included demographic
      characteristics, offense type, drug involvement, various neighborhood variables
      (e.g., concentrated disadvantage, residential mobility), and spatial contagion
      (i.e., proximity to others who become reincarcerated). Using geographic
      information systems (GIS) and logistic regression modeling, our results showed
      that the likelihood of reincarceration was increased with male gender, drug
      involvement, offense type, and living in areas with high rates of recidivism.
      Older offenders and those convicted of violent or drug offenses were less likely
      to be reincarcerated. For violent offenders, drug involvement, age, and spatial
      contagion were particular risk factors for reincarceration. None of the
      neighborhood environment variables were associated with increased risk of
      reincarceration. Reentry programs need to particularly address substance abuse
      issues of ex-offenders as well as take into consideration their residential
      locations.

PMID- 24443613
TI  - Fence Methods for Backcross Experiments.
AB  - Model search strategies play an important role in finding simultaneous
      susceptibility genes that are associated with a trait. More particularly, model
      selection via the information criteria, such as the BIC with modifications, have
      received considerable attention in quantitative trait loci (QTL) mapping.
      However, such modifications often depend upon several factors, such as sample
      size, prior distribution, and the type of experiment, e.g., backcross,
      intercross. These changes make it difficult to generalize the methods to all
      cases. The fence method avoids such limitations with a unified approach, and
      hence can be used more broadly. In this paper, this method is studied in the case
      of backcross experiments throughout a series of simulation studies. The results
      are compared with those of the modified BIC method as well as some of the most
      popular shrinkage methods for model selection.

PMID- 24443614
TI  - The Effects of General Social Support and Social Support for Racial
      Discrimination on African American Women's Well-Being.
AB  - The present longitudinal study examined the role of general and tailored social
      support in mitigating the deleterious impact of racial discrimination on
      depressive symptoms and optimism in a large sample of African American women.
      Participants were 590 African American women who completed measures assessing
      racial discrimination, general social support, tailored social support for racial
      discrimination, depressive symptoms, and optimism at two time points (2001-2002
      and 2003-2004). Our results indicated that higher levels of general and tailored
      social support predicted optimism one year later; changes in both types of
      support also predicted changes in optimism over time. Although initial levels of
      neither measure of social support predicted depressive symptoms over time,
      changes in tailored support predicted changes in depressive symptoms. We also
      sought to determine whether general and tailored social support "buffer" or
      diminish the negative effects of racial discrimination on depressive symptoms and
      optimism. Our results revealed a classic buffering effect of tailored social
      support, but not general support on depressive symptoms for women experiencing
      high levels of discrimination.

PMID- 24443615
TI  - Anxiety and Disordered Eating.

PMID- 24443616
TI  - Self-Esteem Reactivity Among Mothers of Children with Attention
      Deficit/Hyperactivity Disorder: The Moderating Role of Depression History.
AB  - This study examined self-esteem reactivity to a variety of contextual cues in a
      sample of women prone to depression. Participants were 49 mothers of children
      with attention-deficit/hyperactivity disorder. Across a 9-month time-period,
      participants completed weekly measures of self-esteem, perceived stress, positive
      and negative affect, and child disruptive behavior. Results indicated that
      mothers reported lower self-esteem during weeks they experienced greater stress,
      lower positive affect, higher negative affect, and more inattentive, overactive,
      and oppositional behavior in their children. Depression history moderated these
      relationships such that mothers with prior histories of depression reported
      greater self-esteem reactivity to these cues than never depressed mothers.

PMID- 24443618
TI  - Research-based PAM50 subtype predictor identifies higher responses and improved
      survival outcomes in HER2-positive breast cancer in the NOAH study.
AB  - PURPOSE: We report a retrospective exploratory analysis of the association of the
      research-based prediction analysis of microarray 50 (PAM50) subtype predictor
      with pathologic complete response (pCR) and event-free survival (EFS) in women
      enrolled in the NeOAdjuvant Herceptin (NOAH) trial. EXPERIMENTAL DESIGN: Gene
      expression profiling was performed using RNA from formalin-fixed paraffin
      embedded core biopsies from 114 pretreated patients with HER2-positive (HER2(+))
      tumors randomized to receive neoadjuvant doxorubicin/paclitaxel (AT) followed by
      cyclophosphamide/methotrexate/fluorouracil (CMF), or the same regimen in
      combination with trastuzumab for one year. A control cohort of 42 patients with
      HER2-negative tumors treated with AT-CMF was also included. The PAM50 subtypes,
      the PAM50 proliferation score, and the PAM50 risk of relapse score based on
      subtype (RORS) and subtype and proliferation (RORP) were evaluated. RESULTS: HER2
      enriched (HER2-E) tumors predominated within HER2(+) disease, although all PAM50
      intrinsic subtypes were identified across the three cohorts. The OR for achieving
      pCR with trastuzumab-based chemotherapy for HER2(+)/HER2-E and HER2(+)/RORP-high
      were 5.117 (P = 0.009) and 8.469 (P = 0.025), respectively, compared with
      chemotherapy only. The pCR rates of HER2(+)/HER2-E and HER2(+)/RORP-high after
      trastuzumab-based chemotherapy were 52.9% and 75.0%, respectively. A
      statistically nonsignificant trend was observed for more pronounced survival
      benefit with trastuzumab in patients with HER2(+)/HER2-E and HER2(+)/RORP-high
      tumors compared with patients with HER2(+)/non-HER2-E and HER2(+)/non-RORP-high
      tumors, respectively. CONCLUSIONS: As determined by EFS and pCR, patients with
      HER2(+)/HER2-E tumors, or HER2(+)/RORP-high tumors, benefit substantially from
      trastuzumab-based chemotherapy. The clinical value of this genomic test within
      HER2(+) disease warrants further investigation.

PMID- 24443619
TI  - Simplification and Saving.
AB  - The daunting complexity of important financial decisions can lead to
      procrastination. We evaluate a low-cost intervention that substantially
      simplifies the retirement savings plan participation decision. Individuals
      received an opportunity to enroll in a retirement savings plan at a pre-selected
      contribution rate and asset allocation, allowing them to collapse a
      multidimensional problem into a binary choice between the status quo and the pre
      selected alternative. The intervention increases plan enrollment rates by 10 to
      20 percentage points. We find that a similar intervention can be used to increase
      contribution rates among employees who are already participating in a savings
      plan.

PMID- 24443620
TI  - Phonemes and Production.
AB  - This comment offers observations that support Hickok's claim that phoneme sized
      representations are involved more in speech production than speech perception,
      but notes that languages may vary with regard to the importance of the phoneme.

PMID- 24443621
TI  - Memory availability and referential access.
AB  - Most theories of coreference specify linguistic factors that modulate antecedent
      accessibility in memory; however, whether non-linguistic factors also affect
      coreferential access is unknown. Here we examined the impact of a non-linguistic
      generation task (letter transposition) on the repeated-name penalty, a processing
      difficulty observed when coreferential repeated names refer to syntactically
      prominent (and thus more accessible) antecedents. In Experiment 1, generation
      improved online (event-related potentials) and offline (recognition memory)
      accessibility of names in word lists. In Experiment 2, we manipulated generation
      and syntactic prominence of antecedent names in sentences; both improved online
      and offline accessibility, but only syntactic prominence elicited a repeated-name
      penalty. Our results have three important implications: first, the form of a
      referential expression interacts with an antecedent's status in the discourse
      model during coreference; second, availability in memory and referential
      accessibility are separable; and finally, theories of coreference must better
      integrate known properties of the human memory system.

PMID- 24443622
TI  - Pilot task-based assessment of noise levels among firefighters.
AB  - PURPOSE: Over one million American firefighters are routinely exposed to various
      occupational hazards agents. While efforts have been made to identify and reduce
      some causes of injuries and illnesses among firefighters, relatively little has
      been done to evaluate and understand occupational noise exposures in this group.
      The purpose of this pilot study was to apply a task-based noise exposure
      assessment methodology to firefighting operations to evaluate potential noise
      exposure sources, and to use collected task-based noise levels to create noise
      exposure estimates for evaluation of risk of noise-induced hearing loss by
      comparison to the 8-hr and 24-hr recommended exposure limits (RELs) for noise of
      85 and 80.3 dBA, respectively. METHODS: Task-based noise exposures (n=100
      measurements) were measured in three different fire departments (a rural
      department in Southeast Michigan and suburban and urban departments in Northern
      California). These levels were then combined with time-at-task information
      collected from firefighters to estimate 8-hr noise exposures for the rural and
      suburban fire departments (n=6 estimates for each department). Data from 24-hr
      dosimetry measurements and crude self-reported activity categories from the urban
      fire department (n=4 measurements) were used to create 24-hr exposure estimates
      to evaluate the bias associated with the task-based estimates. RESULTS: Task
      based noise levels were found to range from 82-109 dBA, with the highest levels
      resulting from use of saws and pneumatic chisels. Some short (e.g., 30 min)
      sequences of common tasks were found to result in nearly an entire allowable
      daily exposure. The majority of estimated 8-hr and 24-hr exposures exceeded the
      relevant recommended exposure limit. Predicted 24-hr exposures showed substantial
      imprecision in some cases, suggesting the need for increased task specificity.
      CONCLUSIONS: The results indicate potential for overexposure to noise from a
      variety of firefighting tasks and equipment, and suggest a need for further
      exposure characterization and additional hearing loss prevention efforts.
      RELEVANCE TO INDUSTRY: Firefighters may be at risk of noise-induced hearing loss,
      which can affect their fitness for duty and ability to respond effectively to
      emergencies. The results of this study suggest that additional efforts at hearing
      loss prevention among firefighters are warranted.

PMID- 24443623
TI  - Therapy for Childhood Sexual Abuse Survivors using Attachment and Family Systems
      Theory Orientations.
AB  - The aim of this paper is to understand the effects of childhood sexual abuse on a
      survivor's later life. For understanding and treating the emotional distress and
      interpersonal problems resulting from childhood sexual abuse, attachment theory
      provides a valuable framework. When this framework is combined with family
      systems theory, it can help therapists understand the family context where sexual
      abuse occurs and how this affects health and functioning throughout the lifespan.
      Case examples of female adult sexual abuse survivors are also explored, with
      insight from the intersection of systems and attachment theories.

PMID- 24443624
TI  - Quantifying Digit Force Vector Coordination during Precision Pinch.
AB  - A methodology was established to investigate the contact mechanics of the thumb
      and the index finger at the digit-object interface during precision pinch. Two
      force/torque transducers were incorporated into an apparatus designed to overcome
      the thickness of each transducer and provide a flexible pinch span for digit
      placement and force application. To demonstrate the utility of the device, five
      subjects completed a pinch task with the pulps of their thumb and index finger.
      Inter-digit force vector coordination was quantified by examining the 1) force
      vector component magnitudes, 2) resultant force vector magnitudes, 3)
      coordination angle - the angle formed by the resultant vectors of each digit, 4)
      direction angles - the angle formed by each vector and the coordinate axes, and
      5) center of pressure locations. It was shown that the resultant force magnitude
      of the index finger exceeded that of the thumb by 0.8 +/- 0.3 N and that the
      coordination angle between the digit resultant force vectors was 160.2 +/- 4.6
      degrees . The experimental apparatus and analysis methods provide a valuable tool
      for the quantitative examination of biomechanics and motor control during
      dexterous manipulation.

PMID- 24443625
TI  - Feeding Practices of Mothers from Varied Income and Racial/Ethnic Groups.
AB  - OBJECTIVE: Relatively few investigators have explored the role of maternal
      control in describing the feeding behavior of nonwhite parents of preschool-age
      children. The present study was conducted to examine if controlling feeding
      behaviors (i.e., restriction and pressuring) varied by income (middle vs. low)
      and race/ethnicity (white vs. Hispanic), and if they were associated with the BMI
      of their 4-year-old offspring. METHOD: Responses to the "restriction" and
      "pressure to eat" variables of the Child Feeding Questionnaire were compared
      between 51 white middle-income mothers and 49 Hispanic low-income mothers.
      RESULTS: Mothers from both groups gave predominantly "neutral" ratings in their
      self-reports of feeding practices. However, relative to the Hispanic mothers,
      white mothers indicated significantly less restriction and pressure to eat.
      Higher child BMI was predicted by male gender and being Hispanic. CONCLUSION: The
      utility of maternal feeding practices in predicting child overweight is
      discussed, and the significant association between the conceptually different
      constructs of restriction and pressure to eat is examined.

PMID- 24443626
TI  - Measuring ultrafast protein folding rates from photon-by-photon analysis of
      single molecule fluorescence trajectories.
AB  - Folding and unfolding rates for the ultrafast folding villin subdomain were
      determined from a photon-by-photon analysis of fluorescence trajectories in
      single molecule FRET experiments. One of the obstacles to measuring fast kinetics
      in single molecule fluorescence experiments is blinking of the fluorophores on a
      timescale that is not well separated from the process of interest. By
      incorporating acceptor blinking into a two-state kinetics model, we show that it
      is possible to extract accurate rate coefficients on the microsecond time scale
      for folding and unfolding using the maximum likelihood method of I.V. Gopich and
      A. Szabo. This method yields the most likely parameters of a given model that can
      reproduce the observed photon trajectories. The extracted parameters agree with
      both the decay rate of the donor-acceptor cross correlation function and the
      results of ensemble equilibrium and kinetic experiments using nanosecond laser
      temperature jump.

PMID- 24443627
TI  - EPFR Formation from Phenol adsorption on Al2O3 and TiO2: EPR and EELS studies.
AB  - We have examined the formation of environmentally persistent free radicals
      (EPFRs) from phenol over alumina and titania using both powder and single-crystal
      samples. Electron paramagnetic resonance (EPR) studies of phenol adsorbed on
      metal oxide powders indicates radical formation on both titania and alumina, with
      both oxides forming one faster-decaying species (lifetime on the order of 50-100
      hours) and one slower-decayng species (lifetimes on the order of 1000 hours or
      more). Electron energy loss spectroscopy (EELS) measurements comparing
      physisorbed phenol on single-crystal TiO2(110) to phenoxyl radicals on the same
      substrate indicate distinct changes in the pi-pi* transitions from phenol after
      radical formation. The identical shifts are observed from EELS studies of
      phenoxyl radicals on ultrathin alumina grown on NiAl(110), indicating that this
      shift in the pi-pi* transition may be taken as a general hallmark of phenoxyl
      radical formation.

PMID- 24443628
TI  - Developing the Psychological Strain Scales (PSS): Reliability, Validity, and
      Preliminary Hypothesis Tests.
AB  - Since its inception, the Strain Theory of Suicide has been tested and supported
      in a number of empirical studies. This social psychological theory can be
      employed as a complementary conceptualization to account for suicidal behaviors
      as well as mental disorders. However, the lack of consistent measurements of the
      strains limits the application of the theory in scientific research. Our research
      team has developed such scales for future testing of the Strain Theory of Suicide
      in a more systematic approach. For the initial items to measure the four strains
      (value, aspiration, deprivation, and coping), we solicited approximately 40 items
      for each strain with high face validity by about 30 fellow researchers. A
      preliminary examination of about 160 items for consistency and validity, with a
      sample of about 300 college students, yielded 20 consistent items for each of the
      four strain scales. Then, a second study was conducted at a different university
      with approximately 500 students to further streamline each of the four strain
      scales and test the validity of each with corresponding established scales and
      variables. As a result, 15 items were selected for each of the four Psychological
      Strain Scales (PSS). In correlation and multiple regression analyses, we found
      support for the hypotheses regarding the positive associations between
      psychological strains measured by the PSS and psychopathology including suicidal
      ideation. Follow up research with the new scales needs to be carried out in order
      to test the effects of psychological strains on suicide and mental disorders for
      various populations.

PMID- 24443629
TI  - COUNTERACTING AGE STEREOTYPES: A SELF-AWARENESS MANIPULATION.
AB  - The major goals of the present study were to (a) examine age differences in
      susceptibility to age stereotypes and (b) test a self-awareness manipulation in
      counteracting age stereotypes. Young and older adults read two sets of
      descriptors that only differed in the to-be-ignored age-related information. In
      the high self-awareness condition, participants saw themselves via a computer
      video camera. In the low self-awareness condition, they saw prerecorded images of
      a stranger. Overall, older adults were more likely than young adults to make age
      stereotypical judgments in the low self-awareness condition. No age differences
      were found in the high self-awareness condition.

PMID- 24443630
TI  - Using resonance Raman cross-section data to estimate the spin state populations
      of Cytochromes P450.
AB  - The cytochromes P450 (CYPs) are heme proteins responsible for the oxidation of
      xenobiotics and pharmaceuticals and the biosynthesis of essential steroid
      products. In all cases, substrate binding initiates the enzymatic cycle,
      converting ferric low spin (LS) to high-spin (HS), with the efficiency of the
      conversion varying widely for different substrates, so documentation of this
      conversion for a given substrate is an important objective. Resonance Raman (rR)
      spectroscopy can effectively yield distinctive frequencies for the nu3 "spin
      state marker" bands. Here, employing a reference cytochrome P450 (CYP101), the
      intensities of the nu3 modes (ILS) and (IHS) relative to an internal standard
      (sodium sulfate) yield relative populations for the two spin states; i.e., a
      value of 1.24 was determined for the ratio of the relative cross sections for the
      nu3 modes. Use of this value was then shown to permit a reliable calculation of
      relative populations of the two spin states from rR spectra of several other
      Cytochromes P450. The importance of this work is that, using this information, it
      is now possible to conveniently document by rR the spin state population without
      conducting separate experiments requiring different analytical methods,
      instrumentation and additional sample.

PMID- 24443631
TI  - HOW DO IMMIGRANTS SPEND THEIR TIME?: THE PROCESS OF ASSIMILATION.
AB  - Sharp differences in time use by nativity emerge when activities are
      distinguished by incidence and intensity in recent U.S. data. A model with daily
      fixed costs for assimilating activities predicts immigrants are less likely than
      natives to undertake such activities on a given day; but those who do will spend
      relatively more time on them. Activities such as purchasing, education, and
      market work conform to the model. Other results suggest that fixed costs for
      assimilating activities are higher for immigrants with poor English proficiency
      or who originate in less developed countries. An analysis of comparable
      Australian data yields similar results.

PMID- 24443632
TI  - Do Peers Contribute to the Achievement Gap between Vietnamese-American and
      Mexican-American Adolescents?
AB  - Documented associations between academic and social functioning have been
      inconsistent. These discrepancies may reflect the moderating role of
      sociocultural context. In this study, we examined ethnicity and gender as
      moderators of this relation. We collected peer nominations, GPA from school
      records, and self-report questionnaires for 519 Vietnamese-American and Mexican
      American middle school students (mean age = 12.7 years). Using general linear
      modeling, we found that academic and social functioning were more strongly and
      positively linked for Vietnamese-Americans relative to Mexican-Americans, and for
      girls relative to boys. We also examined group differences in achievement values,
      and found that Vietnamese-Americans were more likely to admire and be friends
      with high-achieving peers. The results suggest that peers provide one context in
      which ethnic and gender differences in achievement values emerge, and
      interventions aimed at reducing the achievement gap may benefit from
      incorporating a focus on peers.

PMID- 24443633
TI  - Development of a Headlight Glare Simulator for a Driving Simulator.
AB  - We describe the design and construction of a headlight glare simulator to be used
      with a driving simulator. The system combines a modified programmable off-the
      shelf LED display board and a beamsplitter so that the LED lights, representing
      the headlights of oncoming cars, are superimposed over the driving simulator
      headlights image. Ideal spatial arrangement of optical components to avoid
      misalignments of the superimposed images is hard to achieve in practice and
      variations inevitably introduce some parallax. Furthermore, the driver's viewing
      position varies with driver's height and seating position preferences exacerbate
      such misalignment. We reduce the parallax errors using an intuitive calibration
      procedure (simple drag-and-drop alignment of nine LED positions with calibration
      dots on the screen). To simulate the dynamics of headlight brightness changes
      when two vehicles are approaching, LED intensity control algorithms based on both
      headlight and LED beam shapes were developed. The simulation errors were
      estimated and compared to real-world headlight brightness variability.

PMID- 24443634
TI  - Multidimensional Measures of Response and Fluctuations in Stochastic Dynamical
      Systems.
AB  - A new class of experiments is proposed which involve multiple measurements
      combined with multiple perturbations of a nonlinear classical complex system. A
      family of multipoint n + m - 1 dimensional measures R(n,m) that provide
      complimentary information on complex systems is obtained by combining m non
      linear stimuli and n measurements. They represent the combined effect of causal
      response and noncausal spontaneous fluctuations. The proposed signals can be
      measured either in the frequency domain or in the time domain. Generalized
      fluctuation-dissipation relations which hold in the nonlinear regime restrict the
      number of independent techniques. Two dimensional correlation plots derived from
      such measurements can reveal various types of couplings among collective modes.

PMID- 24443636
TI  - Sensory Processing Difficulties, Behavioral Problems, and Parental Stress in a
      Clinical Population of Young Children.
AB  - This study examined the relationship between sensory processing difficulties,
      parental stress, and behavioral problems in a clinical sample of young children
      with developmental and behavioral difficulties. We hypothesized that a high rate
      of sensory processing difficulties would be found, that there would be a high
      rate of comorbidity between sensory processing difficulties and behavioral
      problems, and that children's sensory processing difficulties and parental stress
      would be highly correlated. Parents of 59 children ages two to five who attended
      an out-patient clinic in a low income, urban community completed the Child
      Behavior Checklist, Parental Stress Inventory-Short Form and the Short Sensory
      Profile. Children in this clinical population showed a high prevalence (55.9%) of
      sensory processing difficulties, a significantly higher rate than previously
      reported. Sensory processing deficits were correlated with behavioral
      difficulties and parental stress levels-suggesting that as sensory processing
      difficulties increase, so do behavioral difficulties and parental stress. Parents
      of children with sensory processing deficits had significantly higher levels of
      parental stress than parents of children without sensory deficits. Parenting
      stress levels were also clinically elevated for the cohort of children in which
      sensory processing difficulties and behavioral concerns co-existed. These
      findings suggest that treatment outcomes might improve and parental stress could
      be reduced if mental health clinicians were trained to identify and address
      sensory problems. This could result in more children being screened and treated
      for sensory processing difficulties and an eventual reduction in the rates of
      parental stress.

PMID- 24443637
TI  - Preventing Maltreatment with a Community-Based Implementation of Parent-Child
      Interaction Therapy.
AB  - The purpose of this study was to examine rates of child abuse and neglect reports
      following a community implementation of Parent-Child Interaction Therapy (PCIT),
      an evidence-supported intervention for the prevention of maltreatment. Among a
      group of families receiving PCIT, predictors of reports were examined including
      family demographics, course of treatment, changes in clinical measures, and
      caregiver report for prior maltreatment victimization and perpetration.
      Participants (n=120) included families at-risk for future maltreatment with and
      without prior maltreatment history. Agency case records were linked with state
      administrative records of child welfare reports. Time to follow-up ranged from 13
      40 months. Bivariate and multivariate survival analyses are used to model risk
      for a later report. During the follow-up period, 12.5% of families had a report
      for physical abuse or neglect. Reports of prior victimization as a child and
      prior perpetration as an adult were strong predictors of a report of perpetration
      after PCIT. Dosage of PCIT and change in clinical measures did not increase risk
      for a later report. PCIT can be an effective intervention for preventing
      maltreatment. Family history of child welfare involvement is a prominent factor
      in assessing risk for future involvement.

PMID- 24443639
TI  - A Separable Model for Dynamic Networks.
AB  - Models of dynamic networks - networks that evolve over time - have manifold
      applications. We develop a discrete-time generative model for social network
      evolution that inherits the richness and flexibility of the class of exponential
      family random graph models. The model - a Separable Temporal ERGM (STERGM) -
      facilitates separable modeling of the tie duration distributions and the
      structural dynamics of tie formation. We develop likelihood-based inference for
      the model, and provide computational algorithms for maximum likelihood
      estimation. We illustrate the interpretability of the model in analyzing a
      longitudinal network of friendship ties within a school.

PMID- 24443638
TI  - Major Causes of the Rapid Longevity Extension in Postwar Japan.

PMID- 24443640
TI  - EXTREME VALUE THEORY WITH OPERATOR NORMING.
AB  - A new approach to extreme value theory is presented for vector data with heavy
      tails. The tail index is allowed to vary with direction, where the directions are
      not necessarily along the coordinate axes. Basic asymptotic theory is developed,
      using operator regular variation and extremal integrals. A test is proposed to
      judge whether the tail index varies with direction in any given data set.

PMID- 24443635
TI  - Research Methods in Child Disaster Studies: A Review of Studies Generated by the
      September 11, 2001, Terrorist Attacks; the 2004 Indian Ocean Tsunami; and
      Hurricane Katrina.
AB  - BACKGROUND: A comprehensive review of the design principles and methodological
      approaches that have been used to make inferences from the research on disasters
      in children is needed. OBJECTIVE: To identify the methodological approaches used
      to study children's reactions to three recent major disasters-the September 11,
      2001, attacks; the 2004 Indian Ocean Tsunami; and Hurricane Katrina. METHODS:
      This review was guided by a systematic literature search. RESULTS: A total of 165
      unduplicated empirical reports were generated by the search and examined for this
      review. This included 83 references on September 11, 29 on the 2004 Tsunami, and
      53 on Hurricane Katrina. CONCLUSIONS: A diversity of methods has been brought to
      bear in understanding children's reactions to disasters. While cross-sectional
      studies predominate, pre-event data for some investigations emerged from archival
      data and data from studies examining non-disaster topics. The nature and extent
      of the influence of risk and protective variables beyond disaster exposure are
      not fully understood due, in part, to limitations in the study designs used in
      the extant research. Advancing an understanding of the roles of exposure and
      various individual, family, and social factors depends upon the extent to which
      measures and assessment techniques are valid and reliable, as well as on data
      sources and data collection designs. Comprehensive assessments that extend beyond
      questionnaires and checklists to include interviews and cognitive and biological
      measures to elucidate the negative and positive effects of disasters on children
      also may improve the knowledge base.

PMID- 24443641
TI  - Toxic coral gobies reduce the feeding rate of a corallivorous butterflyfish on
      Acropora corals.
AB  - The obligate coral-dwelling gobiid genus Gobiodon inhabits Acropora corals and
      has developed various physiological, morphological and ethological adaptations
      towards this life habit. While the advantages of this coral-fish association are
      well documented for Gobiodon, possible fitness-increasing factors for the host
      coral are unknown. This study examines the influence of coral-dwelling gobies on
      the feeding behaviour of obligate corallivorous butterflyfishes. In an aquarium
      experiment using video observation, the corallivorous butterflyfish Chaetodon
      austriacus fed significantly less on corals inhabited by two Gobiodon species
      compared to unoccupied coral colonies of similar size. The more agonistic species
      G. histrio, which mostly displayed directed movements towards butterflyfishes,
      decreased butterflyfish bite rate by 62-98 % compared to uninhabited colonies.
      For Gobiodon sp. 3, which mostly displayed undirected movements in response to
      visits by C. austriacus, bite rate reduction was 64-68 %. The scale-less skin of
      Gobiodon spp. is covered by mucus that is toxic and multi-functional by reducing
      predation as well as affecting parasite attachment. A choice flume experiment
      suggests that the highly diluted skin mucus of Gobiodon spp. also functions as a
      corallivore repellent. This study demonstrates that Gobiodon spp. exhibit
      resource defence against coral-feeding butterflyfishes and also that coral
      colonies without resident Gobiodon suffer higher predation rates. Although the
      genus Gobiodon is probably a facultative corallivore, this study shows that by
      reducing predation on inhabited colonies by other fishes, these obligate coral
      dwellers either compensate for their own fitness-decreasing impact on host
      colonies or live in a mutualistic association with them.

PMID- 24443642
TI  - Automation and adaptation: Nurses' problem-solving behavior following the
      implementation of bar coded medication administration technology.
AB  - The most common change facing nurses today is new technology, particularly bar
      coded medication administration technology (BCMA). However, there is a dearth of
      knowledge on how BCMA alters nursing work. This study investigated how BCMA
      technology affected nursing work, particularly nurses' operational problem
      solving behavior. Cognitive systems engineering observations and interviews were
      conducted after the implementation of BCMA in three nursing units of a
      freestanding pediatric hospital. Problem-solving behavior, associated problems,
      and goals, were specifically defined and extracted from observed episodes of
      care. Three broad themes regarding BCMA's impact on problem solving were
      identified. First, BCMA allowed nurses to invent new problem-solving behavior to
      deal with pre-existing problems. Second, BCMA made it difficult or impossible to
      apply some problem-solving behaviors that were commonly used pre-BCMA, often
      requiring nurses to use potentially risky workarounds to achieve their goals.
      Third, BCMA created new problems that nurses were either able to solve using
      familiar or novel problem-solving behaviors, or unable to solve effectively.
      Results from this study shed light on hidden hazards and suggest three critical
      design needs: (1) ecologically valid design; (2) anticipatory control; and (3)
      basic usability. Principled studies of the actual nature of clinicians' work,
      including problem solving, are necessary to uncover hidden hazards and to inform
      health information technology design and redesign.

PMID- 24443643
TI  - Land use and climatic factors structure regional patterns in soil microbial
      communities.
AB  - AIM: Although patterns are emerging for macroorganisms, we have limited
      understanding of the factors determining soil microbial community composition and
      productivity at large spatial extents. The overall objective of this study was to
      discern the drivers of microbial community composition at the extent of
      biogeographical provinces and regions. We hypothesized that factors associated
      with land use and climate would drive soil microbial community composition and
      biomass. LOCATION: Great Basin Province, Desert Province and California Floristic
      Province, California, USA. METHODS: Using phospholipid fatty acid analysis, we
      compared microbial communities across eight land-use types sampled throughout the
      State of California, USA (n = 1117). RESULTS: The main factor driving composition
      and microbial biomass was land-use type, especially as related to water
      availability and disturbance. Dry soils were more enriched in Gram-negative
      bacteria and fungi, and wetter soils were more enriched in Gram-positive,
      anaerobic and sulphate-reducing bacteria. Microbial biomass was lowest in
      ecosystems with the wettest and driest soils. Disturbed soils had less fungal and
      more Gram-positive bacterial biomass than wildland soils. However, some factors
      known to influence microbial communities, such as soil pH and specific plant
      taxa, were not important here. MAIN CONCLUSIONS: Distinct microbial communities
      were associated with land-use types and disturbance at the regional extent.
      Overall, soil water availability was an important determinant of soil microbial
      community composition. However, because of the inclusion of managed and irrigated
      agricultural ecosystems, the effect of precipitation was not significant. Effects
      of environmental and management factors, such as flooding, tillage and
      irrigation, suggest that agricultural management can have larger effects on soil
      microbial communities than elevation and precipitation gradients.

PMID- 24443644
TI  - Comparisons of three practical field devices used to measure personal light
      exposures and activity levels.
AB  - This paper documents the spectral and spatial performance characteristics of two
      new versions of the Daysimeter, devices developed and calibrated by the Lighting
      Research Center to measure and record personal circadian light exposure and
      activity levels, and compares them to those of the Actiwatch Spectrum (Philips
      Healthcare). Photometric errors from the Daysimeters and the Actiwatch Spectrum
      were also determined for various types of light sources. The Daysimeters had
      better photometric performance than the Actiwatch Spectrum. To assess differences
      associated with measuring light and activity levels at different locations on the
      body, older adults wore four Daysimeters and an Actiwatch Spectrum for five
      consecutive days. Wearing the Daysimeter or Actiwatch Spectrum on the wrist
      compromises accurate light measurements relative to locating a calibrated
      photosensor at the plane of the cornea.

PMID- 24443645
TI  - Genetics of schizophrenia: What do we know?

PMID- 24443646
TI  - On Channel-Discontinuity-Constraint Routing in Wireless Networks.
AB  - Multi-channel wireless networks are increasingly deployed as infrastructure
      networks, e.g. in metro areas. Network nodes frequently employ directional
      antennas to improve spatial throughput. In such networks, between two nodes, it
      is of interest to compute a path with a channel assignment for the links such
      that the path and link bandwidths are the same. This is achieved when any two
      consecutive links are assigned different channels, termed as "Channel
      Discontinuity-Constraint" (CDC). CDC-paths are also useful in TDMA systems,
      where, preferably, consecutive links are assigned different time-slots. In the
      first part of this paper, we develop a t-spanner for CDC-paths using spatial
      properties; a sub-network containing O(n/theta) links, for any theta > 0, such
      that CDC-paths increase in cost by at most a factor t = (1-2 sin (theta/2))-2. We
      propose a novel distributed algorithm to compute the spanner using an expected
      number of O(n log n) fixed-size messages. In the second part, we present a
      distributed algorithm to find minimum-cost CDC-paths between two nodes using
      O(n2) fixed-size messages, by developing an extension of Edmonds' algorithm for
      minimum-cost perfect matching. In a centralized implementation, our algorithm
      runs in O(n2) time improving the previous best algorithm which requires O(n3)
      running time. Moreover, this running time improves to O(n/theta) when used in
      conjunction with the spanner developed.

PMID- 24443647
TI  - A Reduced Order Model for Whole-Chip Thermal Analysis of Microfluidic Lab-on-a
      Chip Systems.
AB  - This paper presents a Krylov subspace projection-based Reduced Order Model (ROM)
      for whole microfluidic chip thermal analysis, including conjugate heat transfer.
      Two key steps in the reduced order modeling procedure are described in detail,
      including (1) the acquisition of a 3D full-scale computational model in the state
      space form to capture the dynamic thermal behavior of the entire microfluidic
      chip; and (2) the model order reduction using the Block Arnoldi algorithm to
      markedly lower the dimension of the full-scale model. Case studies using
      practically relevant thermal microfluidic chip are undertaken to establish the
      capability and to evaluate the computational performance of the reduced order
      modeling technique. The ROM is compared against the full-scale model and exhibits
      good agreement in spatiotemporal thermal profiles (<0.5% relative error in
      pertinent time scales) and over three orders-of-magnitude acceleration in
      computational speed. The salient model reusability and real-time simulation
      capability renders it amenable for operational optimization and in-line thermal
      control and management of microfluidic systems and devices.

PMID- 24443648
TI  - The Vision-Specific Optimization in Primary and Secondary Control (OPS) Scale.
AB  - OBJECTIVE: To successfully address the challenges of age-related visual
      impairment in rehabilitation and health care settings, it is crucial to gain a
      better understanding of the psychological and behavioral adaptations that occur
      in these populations. The purpose of this study was to modify the Optimization in
      Primary Secondary Control Scale (OPS) (Heckhausen Schulz and Wrosch 1999) to
      assess the utilization of lifespan control strategies among older adults with
      visual impairment. METHOD: The Optimization in Primary and Secondary Control
      Scale (OPS) (Heckhausen et al. 1999) was used to develop a vision-specific
      version of this measure (i.e., VIS-OPS). The VIS-OPS was administered to older
      adults with recent vision loss (N = 364; Mean age = 82.9 years). Theory-driven
      confirmatory factor analysis was used to help refine the instrument and confirm
      the scale's four-factor structure. RESULTS: Items were removed from three of the
      four VIS-OPS subscales due to low squared-multiple correlations and poor model
      fit. Inter-item reliabilities for the resultant subscales ranged from 0.61 to
      0.72. The final four-factor model fit the data well (RMSEA = .06, 90% CI .05-
      .06), with all items loading significantly on their associated factors (i.e.
      subscales). Correlational analyses provided criterion-related validity for the
      VIS-OPS with disability and psychosocial functioning measures in the expected
      directions. CONCLUSIONS: The VIS-OPS will allow researchers to more
      systematically and precisely measure control strategy use in reference to
      specific challenges associated with visual impairment, and may serve as a model
      for examining control strategy use in the context of other disabilities.

PMID- 24443649
TI  - Advances in Doppler OCT.
AB  - We review the principle and some recent applications of Doppler optical coherence
      tomography (OCT). The advances of the phase-resolved Doppler OCT method are
      described. Functional OCT algorithms which are based on an extension of the phase
      resolved scheme are also introduced. Recent applications of Doppler OCT for
      quantification of flow, imaging of microvasculature and vocal fold vibration, and
      optical coherence elastography are briefly discussed.

PMID- 24443650
TI  - Looking Forward: The Promise of Widespread Implementation of Parent Training
      Programs.
AB  - Over the past quarter century, researchers have developed a body of parent
      training programs that have proven effective in reducing child behavior problems,
      but few of these have made their way into routine practice. This article
      describes the long and winding road of implementation as applied to children's
      mental health. Adopting Rogers' (1995) diffusion framework and Fixsen and
      colleagues' implementation framework (Fixsen, Naoom, Blase, Friedman, & Wallace,
      2005), we review more than a decade of research on the implementation of Parent
      Management Training-Oregon Model (PMTO). Data from U.S. and international PMTO
      implementations are used to illustrate the payoffs and the challenges of making
      empirically supported interventions routine practice in the community.
      Technological advances that break down barriers to communication across
      distances, the availability of efficacious programs suitable for implementation,
      and the urgent need for high quality mental health care provide strong rationales
      for prioritizing implementation. Over the next quarter of a century, the
      challenge is to reduce the prevalence of children's psychopathology by creating
      science-based delivery systems to reach families in need, everywhere. 

PMID- 24443651
TI  - Links Between the Intuitive Sense of Number and Formal Mathematics Ability.
AB  - Humans share with other animals a system for thinking about numbers in an
      imprecise and intuitive way. The Approximate Number System (ANS) that underlies
      this thinking is present throughout the lifespan, is entirely nonverbal, and
      supports basic numerical computations like comparing, adding, and subtracting
      quantities. Humans, unlike other animals, also have a system for representing
      exact numbers. This linguistically mediated system is slowly mastered over the
      course of many years and provides the basis for most of our formal mathematical
      thought. A growing body of evidence suggests that the nonverbal ANS and the
      culturally invented system of exact numbers are fundamentally linked. In this
      article, we review evidence for this relationship, describing how group and
      individual differences in the ANS correlate with and even predict formal math
      ability. In this way, we illustrate how a system of ancient core knowledge may
      serve as a foundation for more complex mathematical thought.

PMID- 24443652
TI  - Drugs acting on the pregnant uterus.
AB  - In this review we overview the mechanisms responsible for uterine contractility
      and relaxation. We then use this as the basis for discussing the two major
      uterotonins, oxytocin and prostaglandins followed by currently available
      (although often unlicensed) tocolytics; progesterone, magnesium, calcium channel
      blockers, oxytocin receptor blockers, beta-adrenergic receptor agonists,
      prostaglandin synthesis inhibitors and nitric oxide donors. In this brief review
      we have concentrated on the most important mechanisms of action and data obtained
      on human tissue. By focussing on mechanisms, meta-analyses and Cochrane
      literature reviews, our aim is to provide insight for clinical usefulness, and
      highlight where further research is required and where the targets may be.

PMID- 24443653
TI  - Towards Deeper Research and Better Policy for Healthy Aging --Using the Unique
      Data of Chinese Longitudinal Healthy Longevity Survey.
AB  - The objectives of this review article are to facilitate deeper research and
      better policy analysis for healthy aging, which not only means surviving to old
      ages in good health, but also mean the economics and society of our country would
      be aging healthily, with sound policy and intervention programs. Toward these
      objectives, we introduce the Chinese Longitudinal Healthy Longevity Survey
      (CLHLS), which has been conducted by Center for Healthy Aging and Development
      Studies, National School of Development of Peking University since 1998. We
      present a comprehensive and summarized introduction of the CLHLS study design,
      sample distributions, contents, general quality assessment and availability of
      the CLHLS data collected. Such an introduction would be helpful for our
      colleagues who may be interested in using this unique and more-than-fourteen-year
      longitudinal survey data resource for deeper interdisciplinary research and
      better policy analysis on healthy aging. To illustrate how the unique data
      resources of CLHLS may be useful, we also summarize and discuss ten selected
      healthy aging policy related research based on data from the CLHLS. Finally, we
      discussed the future perspectives using the unique and rich CLHLS datasets.

PMID- 24443654
TI  - Charge Photo-Accumulation and Photocatalytic Hydrogen Evolution Under Visible
      Light at an Iridium(III)-Photosensitized Polyoxotungstate.
AB  - Steady-state irradiation under visible light of a covalent Ir(III)
      photosensitized polyoxotungstate is reported. In the presence of a sacrificial
      electron donor, the photolysis leads to the very efficient photoreduction of the
      polyoxometalate. Successive formation of the one-electron and two-electron
      reduced species, which are unambiguously identified by comparison with
      spectroelectrochemical measurements, is observed with a significantly faster rate
      reaction for the formation of the one-electron reduced species. The kinetics of
      the photoreduction, which are correlated to the reduction potentials of the
      polyoxometalate (POM), can be finely tuned by the presence of an acid. Indeed
      light-driven formation of the two-electron reduced POM is considerably
      facilitated in the presence of acetic acid. The system is also able to perform
      photocatalytic hydrogen production under visible light without significant loss
      of performance over more than 1 week of continuous photolysis and displays higher
      photocatalytic efficiency than the related multi-component system, outlining the
      decisive effect of the covalent bonding between the POM and the photosensitizer.
      This functional and modular system constitutes a promising step for the
      development of charge photoaccumulation devices and subsequent
      photoelectrocatalysts for artificial photosynthesis.

PMID- 24443655
TI  - Total isothiocyanate yield from raw cruciferous vegetables commonly consumed in
      the United States.
AB  - Dietary isothiocyanates are a group of promising chemopreventive agents obtained
      primarily from cruciferous vegetables. Due to their potent chemopreventive and/or
      anti-cancer activities, there is a growing interest in assessing dietary
      isothiocyanate exposure and its impact on human health. Using the HPLC-based
      cyclocondensation assay, the current study measured total isothiocyanate yield
      from raw cruciferous vegetables. A total of 73 samples comprising nine types of
      cruciferous vegetables were analyzed. We observed a wide range of isothiocyanate
      content across the individual vegetables with an average level of 16.2 MUmol/100g
      wet weight, ranging from 1.5 MUmol in raw cauliflower to 61.3 MUmol in raw
      mustard greens. The data represent the maximum amount of isothiocyanates released
      from the intake of raw cruciferous vegetables. Given that the vegetables assayed
      in this study include the most commonly consumed cruciferous vegetables in
      western diets, the data may be particularly useful in estimation of dietary
      isothiocyanate exposure in these populations. However, due to the variation
      observed within each vegetable, biomarkers such as urinary isothiocyanate level
      may be necessary for accurate estimation of individual exposure.

PMID- 24443656
TI  - Occurrence of gout in rheumatoid arthritis: it does happen! A population-based
      study.
AB  - AIM: It has been a popular belief that gout does not typically occur in patients
      with rheumatoid arthritis (RA). Our aim was to assess the occurrence, prevalence,
      clinical presentation and possible risk factors for gout in patients with RA.
      PATIENTS & METHODS: We retrospectively reviewed a population-based incidence
      cohort of patients who fulfilled 1987 ACR criteria for RA between 1980 and 2007.
      The cumulative prevalence of gout in RA adjusted for the competing risk of death
      was estimated. RESULTS: Among the 813 patients with RA, six were diagnosed with
      gout prior to RA incidence and 22 patients developed gout during a total of 9771
      person-years of follow-up. Nine out of 22 patients had crystal-proven gout. The
      25-year cumulative prevalence of gout diagnosed by clinical criteria in patients
      with RA was 5.3%. CONCLUSION: Gout does occur in patients with rheumatoid
      arthritis, however, at a lower rate than in the general population.

PMID- 24443657
TI  - Plastic deformation, wrinkling, and recovery in microgel multilayers.
AB  - Microgel multi-layer films assembled from anionic particles and linear polycation
      were prepared on elastomeric substrates and their self-healing properties
      studied. Dried films were imaged in situ during mechanical deformation and were
      determined to undergo plastic deformation in response to linear strain, leading
      to film buckling upon strain relaxation. Hydration leads to rapid reorganization
      of the film building blocks, permitting recovery of the film to the undamaged
      state. Additionally, films were determined to heal in the presence of high
      relative humidity environments, suggesting that film swelling and hydration is a
      major factor in the restoration of film integrity, and that full immersion in
      solvent is not required for healing. Films prepared from microgels with lower
      levels of acid content and/or polycation length, factors strongly connected to
      the charge density and presumably the connectivity of the film, also display self
      healing characteristics.

PMID- 24443658
TI  - Hierarchical Linear Models for Energy Prediction using Inertial Sensors: A
      Comparative Study for Treadmill Walking.
AB  - Walking is a commonly available activity to maintain a healthy lifestyle.
      Accurately tracking and measuring calories expended during walking can improve
      user feedback and intervention measures. Inertial sensors are a promising
      measurement tool to achieve this purpose. An important aspect in mapping inertial
      sensor data to energy expenditure is the question of normalizing across
      physiological parameters. Common approaches such as weight scaling require
      validation for each new population. An alternative is to use a hierarchical
      approach to model subject-specific parameters at one level and cross-subject
      parameters connected by physiological variables at a higher level. In this paper,
      we evaluate an inertial sensor-based hierarchical model to measure energy
      expenditure across a target population. We first determine the optimal movement
      and physiological features set to represent data. Periodicity based features are
      more accurate (p<0.1 per subject) when generalizing across populations. Weight is
      the most accurate parameter (p<0.1 per subject) measured as percentage prediction
      error. We also compare the hierarchical model with a subject-specific regression
      model and weight exponent scaled models. Subject-specific models perform
      significantly better (p<0.1 per subject) than weight exponent scaled models at
      all exponent scales whereas the hierarchical model performed worse than both.
      However, using an informed prior from the hierarchical model produces similar
      errors to using a subject-specific model with large amounts of training data
      (p<0.1 per subject). The results provide evidence that hierarchical modeling is a
      promising technique for generalized prediction energy expenditure prediction
      across a target population in a clinical setting.

PMID- 24443659
TI  - Formative evaluation of a mobile liquid portion size estimation interface for
      people with varying literacy skills.
AB  - Chronically ill people, especially those with low literacy skills, often have
      difficulty estimating portion sizes of liquids to help them stay within their
      recommended fluid limits. There is a plethora of mobile applications that can
      help people monitor their nutritional intake but unfortunately these applications
      require the user to have high literacy and numeracy skills for portion size
      recording. In this paper, we present two studies in which the low- and the high
      fidelity versions of a portion size estimation interface, designed using the
      cognitive strategies adults employ for portion size estimation during diet recall
      studies, was evaluated by a chronically ill population with varying literacy
      skills. The low fidelity interface was evaluated by ten patients who were all
      able to accurately estimate portion sizes of various liquids with the interface.
      Eighteen participants did an in situ evaluation of the high-fidelity version
      incorporated in a diet and fluid monitoring mobile application for 6 weeks.
      Although the accuracy of the estimation cannot be confirmed in the second study
      but the participants who actively interacted with the interface showed better
      health outcomes by the end of the study. Based on these findings, we provide
      recommendations for designing the next iteration of an accurate and low literacy
      accessible liquid portion size estimation mobile interface.

PMID- 24443660
TI  - Preliminary long-term follow-up of Mindfulness-based cognitive therapy-induced
      remission of depression.
AB  - Major depressive disorder (MDD) is often chronic and characterized by relapse and
      recurrence despite successful treatments to induce remission. Mindfulness-based
      cognitive therapy (MBCT) was developed as a means of preventing relapse for
      individuals in remission using cognitive interventions. In addition, MBCT has
      preliminarily been found to be useful in treating active depression. This current
      investigation is unique in evaluating the long-term outcome of individuals with
      active depression who achieved remission with MBCT. 18 participants who achieved
      remission after an 8-week MBCT group were seen for evaluation at a mean follow-up
      interval of 48.7 months (SD=10.2) after completing treatment. The current study
      shows that in these participants, the gains achieved after the initial treatment
      including remission of depression, decreased rumination, decreased anxiety, and
      increased mindfulness continued for up to 58.9 months of follow-up. The data
      suggests that all levels of depression from less recurrent and mild to more
      recurrent and severe were responsive to MBCT. The average number of minutes per
      week of continued practice in our cohort was 210, but the number of minutes of
      practice did not correlate with depression outcomes. MBCT's effects may be more
      related to regularity of practice than specific quantity. This study provides a
      preliminary exploration of MBCT's long-term effects, which can aid in future
      research with a typically chronic illness.

PMID- 24443661
TI  - Compounds from Simarouba berteroana which inhibit proliferation of NF1-defective
      cancer cells.
AB  - A neurofibromatosis type 1 (NF1) based bioassay-guided phytochemical
      investigation on Simarouba berteroana led to the isolation of one new canthin-6
      one-9-methoxy-5-O-beta-D-glucopyranoside (1), seven known canthine alkaloids (2
      8), two known quassinoids (9-10) and a known neo-lignan (11). The structures of
      all compounds were established by HRMS, 1D- and 2D-NMR analysis and comparison
      with previously reported data. Most of the compounds inhibited the proliferation
      of an Nf1- and p53-deficient mouse glioma cell line at non-cytotoxic
      concentrations.

PMID- 24443662
TI  - Stories from the road of recovery - How adult, female survivors of childhood
      trauma experience ways to positive change.
AB  - The aim of this study was to explore how female survivors of childhood trauma who
      have sought treatment experience ways to positive change. Little knowledge exists
      regarding the first-person perspective of the recovery process following
      childhood trauma, and getting access to this perspective might contribute to
      better understanding of these processes, hence offering opportunities for health
      promotion. All clients (31, including 3 who dropped out) from six stabilization
      groups for women exposed to human-inflicted traumas were invited to participate
      in the study. Experiences of the recovery process were not restricted to the
      period of receiving treatment, and all clients who volunteered were included in
      the study. Qualitative, in-depth interviews with 13 consenting clients were
      carried out shortly after completion of the group treatment. All interviews were
      transcribed verbatim, and a hermeneutical-phenomenological approach to analysis
      was applied. The analysis resulted in five interrelated, but distinct main
      themes: finding new ways to understand one's emotions and actions, moving from
      numbness toward vital contact, becoming an advocate of one's own needs,
      experiencing increased sense of agency, and staying with difficult feelings and
      choices. The themes support, yet supplement trauma theory, by underlining the
      relationship between emotional contact and meaning-making, while downplaying the
      necessity of symptom elimination in the experience of recovery. The findings also
      underline that the active role trauma survivors play in their processes of
      recovery.

PMID- 24443663
TI  - Pump-Flow-Probe X-Ray Absorption Spectroscopy as a Tool for Studying Intermediate
      States of Photocatalytic Systems.
AB  - A new setup for pump-flow-probe X-ray absorption spectroscopy has been
      implemented at the SuperXAS beamline of the Swiss Light Source. It allows
      recording X-ray absorption spectra with a time resolution of tens of microseconds
      and high detection efficiency for samples with sub-mM concentrations. A
      continuous wave laser is used for the photoexcitation, with the distance between
      laser and X-ray beams and velocity of liquid flow determining the time delay,
      while the focusing of both beams and the flow speed define the time resolution.
      This method is compared with the alternative measurement technique that utilizes
      a 1 kHz repetition rate laser and multiple X-ray probe pulses. Such an experiment
      was performed at beamline 11ID-D of the Advanced Photon Source. Advantages,
      limitations and potential for improvement of the pump-flow-probe setup are
      discussed by analyzing the photon statistics. Both methods, with Co K-edge
      probing were applied to the investigation of a cobaloxime-based photo-catalytic
      reaction. The interplay between optimizing for efficient photoexcitation and time
      resolution as well as the effect of sample degradation for these two setups are
      discussed.

PMID- 24443664
TI  - Kinship Paths To and From the New Europe: A Unified Analysis of Peruvian Adoption
      and Migration.
AB  - This article compares migrants and adoptees of Peruvian origin residing in Europe
      by focusing on their respective movements out of and return to the sending
      country of Peru. First, it analyzes family-based reunifications by drawing on a
      framework from studies of adoption and kinship. Juxtaposing the experiences of
      adoptees with those of migrants reveals how migration, too, may be steeped in
      concerns about kin ties. Next, it analyzes returns of adult adoptees using a
      template modeled on migrant returns, focusing on the centrality of the notion of
      contribution. The article shows how migrants and adoptees contest the constraints
      of European nation-state definitions of kinship intended to limit migration. It
      is based on recent research with Peruvian migrants and adoptees in Spain, as well
      as longer-term research in Peru on migration and adoption.

PMID- 24443665
TI  - RECONSTRUCTION OF FUNCTIONAL ACTIVATIONS IN NEAR INFRARED SPECTROSCOPIC IMAGING.
AB  - We propose a new algorithm for the estimation of functional activations in near
      infrared spectroscopic imaging. Our approach considers the activations to be
      support limited. We simultaneously estimate the function values as well as the
      support from the available measurements. Since this scheme exploit the structure
      inherent to functional imaging, it provide reconstructions with better spatial
      resolution and is more robust to noise.

PMID- 24443666
TI  - IDENTIFICATION OF MYOCARDIAL INFARCTION USING THREE-DIMENSIONAL STRAIN TENSOR
      FRACTIONAL ANISOTROPY.
AB  - Accurate localization of myocardial viability is important in diagnosis of
      infarction. Regional strain function provides excessive information for clinical
      decision making but comparison of strain tensor profiles across differing tissue
      types is usually difficult due to multivariate nature of tensors. It is desirable
      to describe tensors with simplified scalar indices which are more mathematically
      and statistically intuitive. In this work, anisotropy of tensors in healthy and
      experimental infarct regions in a large animal model is assessed and compared to
      directional components of strain tensors which are currently the most popular
      indices in active use. Myocardial strain tensors are computed using zHARP, a
      magnetic resonance (MR) tagging technique that provides quantification of cardiac
      function with direct computation of three-dimensional tensors from two
      dimensional short axis MR images. Fractional anisotropy of strain tensors shows
      high correlation with late gadolinium enhanced images and is capable of
      discrimination between healthy and infarcted regions.

PMID- 24443667
TI  - COMPRESSED SENSING BASED INTENSITY NON-UNIFORMITY CORRECTION.
AB  - We present a compressed sensing based approach to remove gain field from magnetic
      resonance (MR) images of the human brain. During image acquisition, the
      inhomogeneity present in the radio-frequency (RF) coil appears as shading
      artifact in the intensity image. The inhomogeneity poses problem in any automatic
      algorithm that uses intensity as a feature. It has been shown that at low field
      strength, the shading can be assumed to be a smooth field that is composed of low
      frequency components. Thus most inhomogeneity correction algorithms assume some
      kind of explicit smoothness criteria on the field. This sometimes limits the
      performance of the algorithms if the actual inhomogeneity is not smooth, which is
      the case at higher field strength. We describe a model-free, non-parametric patch
      based approach that uses compressed sensing for the correction. We show that
      these features enable our algorithm to perform comparably with a current state of
      the art method N3 on images acquired at low field, while outperforming N3 when
      the image has non-smooth inhomogeneity, such as 7T images.

PMID- 24443668
TI  - EVALUATING SAMPLING STRATEGIES OF DERMOSCOPIC INTEREST POINTS.
AB  - Among the most critical components of a computerized system for automated
      melanoma detection is image sampling and pooling of the extracted features. In
      this paper, we propose a new method for sampling and pooling based on a
      combination of spatial pooling and graph theory features. The performance of the
      new method is evaluated using a dataset of more than 1,500 images representing
      pigmented skin lesions of known pathology. In our comparisons, we include several
      methods ranging from simple and multi-scale sampling on a regular grid to more
      sophisticated approaches, such as blob and curvilinear structure detectors. Our
      results show that, despite its simplicity, simple sampling on a regular grid
      provides highly competitive performance, compared to the more sophisticated
      approaches, while multi-scale sampling yields only trivial improvements. However,
      the proposed method provides significant performance improvement in terms of
      sensitivity and area under the receiver operating characteristic curve (95% t
      test), and the best performance in terms of specificity compared to all other
      methods explored.

PMID- 24443669
TI  - GROUPWISE REGISTRATION OF BREAST DCE-MR IMAGES FOR ACCURATE TUMOR MEASUREMENT.
AB  - The registration of breast DCE-MR images can help correct possible motions during
      image acquisition, and is also important for diagnosis of breast cancer, i.e.,
      discrimination between benign and malignant tumors. However, deformable
      registration of DCE-MR images is challenging due to drastic image contrast change
      over time (especially between pre- and post-contrast images). To improve the
      registration, we propose a novel hierarchical groupwise registration framework by
      specially considering the image characteristics of the breast DCE-MR images.
      Specifically, due to the similarity of post-contrast images, they are jointly
      registered by a groupwise registration method, and then registered together with
      the pre-contrast image by a robust correspondence detection technique based on
      local-steering-kernel features, instead of simple image intensities. Also, to
      accurately register the tumor region, we treat the motion in tumor area and other
      normal tissues differently by delineating rigid motion for tumor while non-rigid
      for other normal tissues. Our experimental results on both real and simulated
      images show that our method can achieve more consistent and accurate registration
      results than the conventional pairwise registration method.

PMID- 24443670
TI  - PRACTICAL PARALLEL IMAGING COMPRESSED SENSING MRI: SUMMARY OF TWO YEARS OF
      EXPERIENCE IN ACCELERATING BODY MRI OF PEDIATRIC PATIENTS.
AB  - For the last two years, we have been experimenting with applying compressed
      sensing parallel imaging for body imaging of pediatric patients. It is a joint
      effort by teams from UC Berkeley, Stanford University and GE Healthcare. This
      paper aims to summarize our experience so far. We describe our acquisition
      approach: 3D spoiled-gradient-echo with poisson-disc random undersampling of the
      phase encodes. Our re-construction approach: l1-SPIRiT, an iterative
      autocalibrating parallel imaging reconstruction that enforces both data
      consistency and joint-sparsity in the wavelet domain. Our implementation: an on
      line parallelized implementation of l1-SPIRiT on multi-core CPU and General
      Purpose Graphics Processors (GPGPU) that achieves sub-minute 3D reconstructions
      with 8-channels. Clinical results showing higher quality reconstruction and
      better diagnostic confidence than parallel imaging alone at accelerations on the
      order of number of coils.

PMID- 24443671
TI  - MANDIBULAR ASYMMETRY CHARACTERIZATION USING GENERALIZED TENSOR-BASED MORPHOMETRY.
AB  - Quantitative assessment of facial asymmetry is crucial for successful planning of
      corrective surgery. We propose a tensor-based morphometry (TBM) framework to
      locate and quantify asymmetry using 3D CBCT images. To this end, we compute a
      rigid transformation between the mandible segmentation and its mirror image,
      which yields global rotation and translation with respect to the cranial base to
      guide the surgery's first stage. Next, we nonrigidly register the rigidly aligned
      images and use TBM methods to locally analyze the deformation field. This yields
      data on the location, amount and direction of "growth" (or "shrinkage") between
      the left and right sides. We visualize this data in a volumetric manner and via
      scalar and vector maps on the mandibular surface to provide the surgeon with
      optimal understanding of the patient's anatomy. We illustrate the feasibility and
      strength of our technique on 3 representative patients with a wide range of
      facial asymmetries.

PMID- 24443672
TI  - RECONSTRUCTION OF THE HUMAN HIPPOCAMPUS IN 3D FROM HISTOLOGY AND HIGH-RESOLUTION
      EX-VIVO MRI.
AB  - In this paper, we present methods for the reconstruction of 3D histological
      volumes of the human hippocampal formation from histology slices. Inter-slice
      alignment is guided by a graph-theoretic approach that minimizes the impact of
      badly distorted slices. The reconstruction is refined by iterative affine and
      deformable co-registration with a high-resolution MRI of the postmortem tissue
      sample. We present an evaluation of reconstruction accuracy that is based on
      measures of similarity between boundaries drawn on both histology and MRI. Our
      methodology is currently being applied to an MRI atlas of the human hippocampal
      formation, in which atlas anatomical labels are derived from segmentation of
      reconstructed histology.

PMID- 24443673
TI  - ACCELERATING CARDIOVASCULAR IMAGING BY EXPLOITING REGIONAL LOW-RANK STRUCTURE VIA
      GROUP SPARSITY.
AB  - Sparse sampling of (k, t)-space has proved useful for cardiac MRI. This paper
      builds on previous work on using partial separability (PS) and spatial-spectral
      sparsity for high-quality image reconstruction from highly undersampled (k, t)
      space data. This new method uses a more flexible control over the PS-induced low
      rank constraint via group-sparse regularization. A novel algorithm is also
      described to solve the corresponding (1,2)-norm regularized inverse problem.
      Reconstruction results from simulated cardiovascular imaging data are presented
      to demonstrate the performance of the proposed method.

PMID- 24443674
TI  - A NOVEL INTRINSIC UNSCENTED KALMAN FILTER FOR TRACTOGRAPHY FROM HARDI*
AB  - The unscented Kalman filter (UKF) was recently introduced in literature for
      simultaneous multi-tensor estimation and tractography. This UKF however was not
      intrinsic to the space of diffusion tensors. Lack of this key property leads to
      inaccuracies in the multi-tensor estimation as well as in tractography. In this
      paper, we propose an novel intrinsic unscented Kalman filter (IUKF) in the space
      of symmetric positive definite matrices, which can be used for simultaneous
      recursive estimation of multi-tensors and tractography from diffusion weighted MR
      data. In addition to being more accurate, IUKF retains all the advantages of UKF
      for instance, multi-tensor estimation is only performed in the places where it is
      needed for tractography, which would be much more efficient than the two stage
      process involved in methods that do tracking post diffusion tensor estimation.
      The accuracy and effectiveness of the proposed method is demonstrated via real
      data experiments.

PMID- 24443675
TI  - MANIFOLD-CONSTRAINED EMBEDDINGS FOR THE DETECTION OF WHITE MATTER LESIONS IN
      BRAIN MRI.
AB  - Brain abnormalities such as white matter lesions (WMLs) are not only linked to
      cerebrovascular disease, but also with normal aging, diabetes and other
      conditions increasing the risk for cerebrovascular pathologies. Obtaining
      quantitative measures which assesses the degree or probability of WML in patients
      is important for evaluating disease burden, and for evaluating its progression
      and response to interventions. In this paper, we introduce a novel approach for
      detecting the presence of WMLs in periventricular areas of the brain using
      manifold-constrained embeddings. The proposed method uses locally linear
      embedding (LLE) to create "normality" distributions in 12 locations of the brain
      where deviations from the manifolds are estimated by calculating geodesic
      distances along locally linear planes in the embedding. A smooth mapping function
      approximating the relationship between ambient and manifold spaces as a joint
      distribution maps unseen test images in the intrinsic space. We create a set of
      low-dimensional embeddings from 876 patches of healthy tissue in 73 subjects and
      test it on 396 patches imaging both WML and healthy areas in 33 subjects with
      diabetes. Experiments highlight the need of nonlinear techniques to learn the
      studied data with detection rates over 85% in true-positives, and the relevance
      of the computed distance for comparing individuals to a specific pathological
      pattern.

PMID- 24443676
TI  - DEPENDENCY PRIOR FOR MULTI-ATLAS LABEL FUSION.
AB  - Multi-atlas label fusion has been widely applied in medical image analysis. To
      reduce the bias in label fusion, we proposed a joint label fusion technique to
      reduce correlated errors produced by different atlases via considering the
      pairwise dependencies between them. Using image similarities from image patches
      to estimate the pairwise dependencies, we showed promising performance. To
      address the unreliability in purely using local image similarity for dependency
      estimation, we propose to improve the accuracy of the estimated dependencies by
      including empirical knowledge, which is learned from the atlases in a leave-one
      out strategy. We apply the new technique to segment the hippocampus from MRI and
      show significant improvement over our initial results.

PMID- 24443677
TI  - 3D single molecule tracking and superresolution microscopy using multifocal plane
      microscopy.
AB  - The study of cellular processes in three-dimensions is severely limited by the
      lack of imaging methodologies that allow for fast 3D tracking of cellular events
      and 3D superresolution imaging of sub-cellular structures. We have developed a 3D
      imaging modality, multifocal plane microscopy (MUM), that provides a powerful
      approach for 3D single molecule tracking and 3D superresolution microscopy. Here
      we review the technical challenges associated with 3D single molecule
      localization that is fundamental to both 3D tracking and 3D superresolution, and
      discuss how MUM overcomes these problems.

PMID- 24443678
TI  - AUTOMATIC MULTI-ATLAS-BASED CARTILAGE SEGMENTATION FROM KNEE MR IMAGES.
AB  - In this paper, we propose a multi-atlas-based method to automatically segment the
      femoral and tibial cartilage from T1 weighted magnetic resonance (MR) knee
      images. The segmentation result is a joint decision of the spatial priors from a
      multi-atlas registration and the local likelihoods within a Bayesian framework.
      The cartilage likelihoods are obtained from a probabilistic k nearest neighbor
      classification. Validation results on 18 knee MR images against the manual expert
      segmentations from a dataset acquired for osteoarthritis research show good
      performance for the segmentation of femoral and tibial cartilage (mean Dice
      similarity coefficient of 75.2% and 81.7% respectively).

PMID- 24443679
TI  - OUT-OF-ATLAS LABELING: A MULTI-ATLAS APPROACH TO CANCER SEGMENTATION.
AB  - Conventional automated segmentation techniques for magnetic resonance imaging
      (MRI) fail to perform in a robust and consistent manner when brain anatomy
      differs wildly from expectations - as is often the case in brain cancers. We
      propose a novel out-of-atlas technique to estimate the spatial extent of abnormal
      brain regions by combining multi-atlas based segmentation with semi-local non
      parametric intensity analysis. In a study with 30 clinically-acquired MRI scans
      of patients with malignant gliomas and 29 atlases of normal anatomy from research
      acquisitions, we demonstrate that this technique robustly identifies cancerous
      regions. The resulting segmentations could be used to study cancer morphometrics
      or guide selection/application/refinement of tumor analysis models or regional
      image quantification approaches.

PMID- 24443680
TI  - AUTOMATIC QUANTIFICATION OF TREE-IN-BUD PATTERNS FROM CT SCANS.
AB  - In this paper, we present a fully automatic method to quantify Tree-in-Bud (TIB)
      patterns for respiratory tract infections. The proposed quantification method is
      based on our previous effort to detect and track TIB patterns with a computer
      assisted detection (CAD) system [9]. In addition to accurately identifying TIB on
      CT, quantifying TIB is important for measuring the volume of affected lung as a
      potantial marker of disease severity. This quantification can be challenging due
      to the complex shape of TIB and high intensity variation contributing mixed
      features. Our proposed quantification method is based on a local scale concept
      such that TIB regions detected via the CAD system are quantified adaptively, and
      volume percentages of the quantified regions are compared to visual scoring of
      participating radiologists. We conducted the experiments with a data set of 94
      chest CTs (laboratory confirmed 39 viral bronchiolitis caused by human
      parainfluenza (HPIV), 34 nontuberculous mycobacterial (NTM), and 21 normal
      control). Experimental results show that the proposed quantification system is
      well suited to the CAD system for detecting TIB patterns. Correlations of
      observer-CAD agreements are reported as (R2 = 0.824, p < 0.01) and (R2 = 0.801, p
      < 0.01) for HPIV and NTM cases, respectively.

PMID- 24443681
TI  - LONGITUDINAL GROWTH MODELING OF DISCRETE-TIME FUNCTIONS WITH APPLICATION TO DTI
      TRACT EVOLUTION IN EARLY NEURODEVELOPMENT.
AB  - We present a new framework for spatiotemporal analysis of parameterized functions
      attributed by properties of 4D longitudinal image data. Our driving application
      is the measurement of temporal change in white matter diffusivity of fiber
      tracts. A smooth temporal modeling of change from a discrete-time set of
      functions is obtained with an extension of the logistic growth model to time
      dependent spline functions, capturing growth with only a few descriptive
      parameters. An unbiased template baseline function is also jointly estimated.
      Solution is demonstrated via energy minimization with an extension to
      simultaneous modeling of trajectories for multiple subjects. The new framework is
      validated with synthetic data and applied to longitudinal DTI from 15 infants.
      Interpretation of estimated model growth parameters is facilitated by
      visualization in the original coordinate space of fiber tracts.

PMID- 24443682
TI  - MODEL-BASED MR PARAMETER MAPPING WITH SPARSITY CONSTRAINT.
AB  - MR parameter mapping (e.g., T1 mapping, T2 mapping, or [Formula: see text]
      mapping) is a valuable tool for tissue characterization. However, its practical
      utility has been limited due to long data acquisition time. This paper addresses
      this problem with a new model-based parameter mapping method, which utilizes an
      explicit signal model and imposes a sparsity constraint on the parameter values.
      The proposed method enables direct estimation of the parameters of interest from
      highly undersampled, noisy k-space data. An algorithm is presented to solve the
      underlying parameter estimation problem. Its performance is analyzed using
      estimation-theoretic bounds. Some representative results from T2 brain mapping
      are also presented to illustrate the performance of the proposed method for
      accelerating parameter mapping.

PMID- 24443683
TI  - SEGMENTATION OF THE COMPLETE SUPERIOR CEREBELLAR PEDUNCLES USING A MULTI-OBJECT
      GEOMETRIC DEFORMABLE MODEL.
AB  - The superior cerebellar peduncles (SCPs) are white matter tracts that serve as
      the major efferent pathways from the cerebellum to the thalamus. With diffusion
      tensor images (DTI), tractography algorithms or volumetric segmentation methods
      have been able to reconstruct part of the SCPs. However, when the fibers cross,
      the primary eigenvector (PEV) no longer represents the primary diffusion
      direction. Therefore, at the crossing of the left and right SCP, known as the
      decussation of the SCPs (dSCP), fiber tracts propagate incorrectly. To our
      knowledge, previous methods have not been able to segment the SCPs correctly. In
      this work, we explore the diffusion properties and seek to volumetrically segment
      the complete SCPs. The non-crossing SCPs and dSCP are modeled as different
      objects. A multi-object geometric deformable model is employed to define the
      boundaries of each piece of the SCPs, with the forces derived from diffusion
      properties as well as the PEV. We tested our method on a software phantom and
      real subjects. Results indicate that our method is able to the resolve the
      crossing and segment the complete SCPs with repeatability.

PMID- 24443684
TI  - A POINT-CORRESPONDENCE APPROACH TO DESCRIBING THE DISTRIBUTION OF IMAGE FEATURES
      ON ANATOMICAL SURFACES, WITH APPLICATION TO ATRIAL FIBRILLATION.
AB  - This paper describes a framework for summarizing and comparing the distributions
      of image features on anatomical shape surfaces in populations. The approach uses
      a point-based correspondence model to establish a mapping among surface positions
      and may be useful for anatomy that exhibits a relatively high degree of shape
      variability, such as cardiac anatomy. The approach is motivated by the MRI-based
      study of diseased, or fibrotic, tissue in the left atrium of atrial fibrillation
      (AF) patients, which has been difficult to measure quantitatively using more
      established image and surface registration techniques. The proposed method is to
      establish a set of point correspondences across a population of shape surfaces
      that provides a mapping from any surface to a common coordinate frame, where
      local features like fibrosis can be directly compared. To establish
      correspondence, we use a previously-described statistical optimization of
      particle-based shape representations. For our atrial fibrillation population, the
      proposed method provides evidence that more intense and widely distributed
      fibrosis patterns exist in patients that do not respond well to radiofrequency
      ablation therapy.

PMID- 24443685
TI  - PATCH BASED INTENSITY NORMALIZATION OF BRAIN MR IMAGES.
AB  - Magnetic resonance (MR) imaging (MRI) is widely used to study the structure of
      human brains. Unlike computed tomography (CT), MR image intensities do not have a
      tissue specific interpretation. Thus images of the same subject obtained with
      either the same imaging sequence on different scanners or with differing
      parameters have widely varying intensity scales. This inconsistency introduces
      errors in segmentation, and other image processing tasks, thus necessitating
      image intensity standardization. Compared to previous intensity normalization
      methods using histogram transformations-which try to find a global one-to-one
      intensity mapping based on histograms-we propose a patch based generative model
      for intensity normalization between images acquired under different scanners or
      different pulse sequence parameters. Our method outperforms histogram based
      methods when normalizing phantoms simulated with various parameters.
      Additionally, experiments on real data, acquired under a variety of scanners and
      acquisition parameters, have more consistent segmentations after our
      normalization.

PMID- 24443686
TI  - MAGNETIC RESONANCE IMAGE SYNTHESIS THROUGH PATCH REGRESSION.
AB  - Magnetic resonance imaging (MRI) is widely used for analyzing human brain
      structure and function. MRI is extremely versatile and can produce different
      tissue contrasts as required by the study design. For reasons such as patient
      comfort, cost, and improving technology, certain tissue contrasts for a cohort
      analysis may not have been acquired during the imaging session. This missing
      pulse sequence hampers consistent neuroanatomy research. One possible solution is
      to synthesize the missing sequence. This paper proposes a data-driven approach to
      image synthesis, which provides equal, if not superior synthesis compared to the
      state-of-the-art, in addition to being an order of magnitude faster. The
      synthesis transformation is done on image patches by a trained bagged ensemble of
      regression trees. Validation was done by synthesizing T2-weighted contrasts from
      T1-weighted scans, for phantoms and real data. We also synthesized 3 Tesla T1
      weighted magnetization prepared rapid gradient echo (MPRAGE) images from 1.5
      Tesla MPRAGEs to demonstrate the generality of this approach.

PMID- 24443687
TI  - DEFORMABLE REGISTRATION OF MACULAR OCT USING A-MODE SCAN SIMILARITY.
AB  - Optical coherence tomography (OCT) of the macular cube has become an increasingly
      important tool for investigating and managing retinal pathology. One important
      new area of investigation is the analysis of anatomic variably across a
      population. Such an analysis on the retina requires the construction of a
      normalized space, which is generally created through deformable registration of
      each subject into a common template. Unfortunately, state-of-the-art 3D
      registration tools fail to adequately spatially normalize retinal OCT images.
      This work proposes a new deformable registration algorithm for OCT images using
      the similarity between pairs of A-mode scans. First, a retinal OCT specific
      affine step is presented, which uses automated landmarks to perform global
      translations and individual rescaling of all the subject's A-mode scans. Then, a
      deformable registration using regularized one-dimensional radial basis functions
      is applied to further align the retinal layers. Results on 15 subjects show the
      improved accuracy of this approach in comparison to state of the art methods with
      respect to registration for labeling. Additional results show the ability to
      generate stereotaxic spaces for retinal OCT.

PMID- 24443688
TI  - SPATIOTEMPORAL MODELING OF DISCRETE-TIME DISTRIBUTION-VALUED DATA APPLIED TO DTI
      TRACT EVOLUTION IN INFANT NEURODEVELOPMENT.
AB  - This paper proposes a novel method that extends spatiotemporal growth modeling to
      distribution-valued data. The method relaxes assumptions on the underlying noise
      models by considering the data to be represented by the complete probability
      distributions rather than a representative, single-valued summary statistics like
      the mean. When summarizing by the latter method, information on the underlying
      variability of data is lost early in the process and is not available at later
      stages of statistical analysis. The concept of 'distance' between distributions
      and an 'average' of distributions is employed. The framework quantifies growth
      trajectories for individuals and populations in terms of the complete data
      variability estimated along time and space. Concept is demonstrated in the
      context of our driving application which is modeling of age-related changes along
      white matter tracts in early neurodevelopment. Results are shown for a single
      subject with Krabbe's disease in comparison with a normative trend estimated from
      15 healthy controls.

PMID- 24443689
TI  - IMAGING GENETICS VIA SPARSE CANONICAL CORRELATION ANALYSIS.
AB  - The collection of brain images from populations of subjects who have been
      genotyped with genome-wide scans makes it feasible to search for genetic effects
      on the brain. Even so, multivariate methods are sorely needed that can search
      both images and the genome for relationships, making use of the correlation
      structure of both datasets. Here we investigate the use of sparse canonical
      correlation analysis (CCA) to home in on sets of genetic variants that explain
      variance in a set of images. We extend recent work on penalized matrix
      decomposition to account for the correlations in both datasets. Such methods show
      promise in imaging genetics as they exploit the natural covariance in the
      datasets. They also avoid an astronomically heavy statistical correction for
      searching the whole genome and the entire image for promising associations.

PMID- 24443690
TI  - CLASSIFYING MEDICAL IMAGES USING MORPHOLOGICAL APPEARANCE MANIFOLDS.
AB  - Input features for medical image classification algorithms are extracted from raw
      images using a series of pre processing steps. One common preprocessing step in
      computational neuroanatomy and functional brain mapping is the nonlinear
      registration of raw images to a common template space. Typically, the
      registration methods used are parametric and their output varies greatly with
      changes in parameters. Most results reported previously perform registration
      using a fixed parameter setting and use the results as input to the subsequent
      classification step. The variation in registration results due to choice of
      parameters thus translates to variation of performance of the classifiers that
      depend on the registration step for input. Analogous issues have been
      investigated in the computer vision literature, where image appearance varies
      with pose and illumination, thereby making classification vulnerable to these
      confounding parameters. The proposed methodology addresses this issue by sampling
      image appearances as registration parameters vary, and shows that better
      classification accuracies can be obtained this way, compared to the conventional
      approach.

PMID- 24443691
TI  - MRI ANALYSIS OF 3D NORMAL AND POST-GLOSSECTOMY TONGUE MOTION IN SPEECH.
AB  - Measuring the internal muscular motion and deformation of the tongue during
      natural human speech is of high interest to head and neck surgeons and speech
      language pathologists. A pipeline for calculating 3D tongue motion from dynamic
      cine and tagged Magnetic Resonance (MR) images during speech has been developed.
      This paper presents the result of a complete analysis of eleven subjects' (seven
      normal controls and four glossectomy patients) global tongue motion during speech
      obtained through MR imaging and processed through the tongue motion analysis
      pipeline. The data is regularized into the same framework for comparison. A
      generalized two-step principal component analysis is used to show the major
      difference between patients' and controls' tongue motions. A test is performed to
      demonstrate the ability of this process to distinguish patient data from control
      data and to show the potential power of quantitative analysis that the tongue
      motion pipeline can achieve.

PMID- 24443692
TI  - INTER-GROUP IMAGE REGISTRATION BY HIERARCHICAL GRAPH SHRINKAGE.
AB  - In this paper, we propose a novel inter-group image registration method to
      register different groups of images (e.g., young and elderly brains)
      simultaneously. Specifically, we use a hierarchical two-level graph to model the
      distribution of entire images on the manifold, with intra-graph representing the
      image distribution in each group and the inter-graph describing the relationship
      between two groups. Then the procedure of inter-group registration is formulated
      as a dynamic evolution of graph shrinkage. The advantage of our method is that
      the topology of entire image distribution is explored to guide the image
      registration. In this way, each image coordinates with its neighboring images on
      the manifold to deform towards the population center, by following the
      deformation pathway simultaneously optimized within the graph. Our proposed
      method has been also compared with other state-of-the-art inter-group
      registration methods, where our method achieves better registration results in
      terms of registration accuracy and robustness.

PMID- 24443693
TI  - IDENTIFYING PATTERNS IN TEMPORAL VARIATION OF FUNCTIONAL CONNECTIVITY USING
      RESTING STATE FMRI.
AB  - Estimating functional brain networks from fMRI data has been the focus of much
      research in recent years. Low sample sizes (time-points) and high dimensionality
      of fMRI has restricted estimation to a temporally averaged connectivity matrix
      per subject, due to which the dynamics of functional connectivity is largely
      unknown. In this paper, we propose a novel method based on constrained matrix
      factorization that addresses two major issues. Firstly, it finds a set of basis
      networks that are the semantic parts of the time-varying whole-brain functional
      networks. The whole-brain network at any point in time, for any subject, is a non
      negative combination of these basis networks. Secondly, significant
      dimensionality reduction is achieved by projecting the data onto this basis,
      facilitating subsequent analysis of temporal dynamics. Results on simulated fMRI
      data show that our method can effectively recover underlying basis networks. We
      apply this method on a normative dataset of resting state fMRI scans. Results
      indicate that the functional connectivity of a subject at any point during the
      scan is composed of combinations of overlapping task-positive/negative pairs of
      sub-networks.

PMID- 24443694
TI  - LOCALLY WEIGHTED TOTAL VARIATION DENOISING FOR RINGING ARTIFACT SUPPRESSION IN
      PET RECONSTRUCTION USING PSF MODELING.
AB  - Iterative reconstruction with point spread function (PSF) modeling improves
      contrast recovery in positron emission tomography (PET) images, but also
      introduces ringing artifacts and over enhancement that is contrast and object
      size dependent. Mitigation of these artifacts is crucial for clinical and
      research purposes. In this work we introduce a new iterative regularized
      reconstruction method that incorporates locally-weighted total variation
      denoising designed to suppress artifacts induced by PSF modeling. The
      reconstruction method is evaluated on a simulated cylindrical phantom and
      preliminary results show that ringing artifacts are suppressed while contrast
      recovery is maintained.

PMID- 24443695
TI  - PROPER ORDERED MESHING OF COMPLEX SHAPES AND OPTIMAL GRAPH CUTS APPLIED TO ATRIAL
      WALL SEGMENTATION FROM DE-MRI.
AB  - Segmentation of the left atrium wall from delayed enhancement MRI is challenging
      because of inconsistent contrast combined with noise and high variation in atrial
      shape and size. This paper presents a method for left-atrium wall segmentation by
      using a novel sophisticated mesh-generation strategy and graph cuts on a proper
      ordered graph. The mesh is part of a template/model that has an associated set of
      learned intensity features. When this mesh is overlaid onto a test image, it
      produces a set of costs on the graph vertices which eventually leads to an
      optimal segmentation. The novelty also lies in the construction of proper ordered
      graphs on complex shapes and for choosing among distinct classes of base
      shapes/meshes for automatic segmentation. We evaluate the proposed segmentation
      framework quantitatively on simulated and clinical cardiac MRI.

PMID- 24443696
TI  - KERNEL-BASED MULTI-TASK JOINT SPARSE CLASSIFICATION FOR ALZHEIMER'S DISEASE.
AB  - Multi-modality imaging provides complementary information for diagnosis of
      neurodegenerative disorders such as Alzheimer's disease (AD) and its prodrome,
      mild cognitive impairment (MCI). In this paper, we propose a kernel-based multi
      task sparse representation model to combine the strengths of MRI and PET imaging
      features for improved classification of AD. Sparse representation based
      classification seeks to represent the testing data with a sparse linear
      combination of training data. Here, our approach allows information from
      different imaging modalities to be used for enforcing class level joint sparsity
      via multi-task learning. Thus the common most representative classes in the
      training samples for all modalities are jointly selected to reconstruct the
      testing sample. We further improve the discriminatory power by extending the
      framework to the reproducing kernel Hilbert space (RKHS) so that nonlinearity in
      the features can be captured for better classification. Experiments on
      Alzheimer's Disease Neuroimaging Initiative database shows that our proposed
      method can achieve 93.3% and 78.9% accuracy for classification of AD and MCI from
      healthy controls, respectively, demonstrating promising performance in AD study.

PMID- 24443697
TI  - ANALYZING IMAGING BIOMARKERS FOR TRAUMATIC BRAIN INJURY USING 4D MODELING OF
      LONGITUDINAL MRI.
AB  - Quantitative imaging biomarkers are important for assessment of impact, recovery
      and treatment efficacy in patients with traumatic brain injury (TBI). To our
      knowledge, the identification of such biomarkers characterizing disease progress
      and recovery has been insufficiently explored in TBI due to difficulties in
      registration of baseline and follow-up data and automatic segmentation of tissue
      and lesions from multimodal, longitudinal MR image data. We propose a new
      methodology for computing imaging biomarkers in TBI by extending a recently
      proposed spatiotemporal 4D modeling approach in order to compute quantitative
      features of tissue change. The proposed method computes surface-based and voxel
      based measurements such as cortical thickness, volume changes, and geometric
      deformation. We analyze the potential for clinical use of these biomarkers by
      correlating them with TBI-specific patient scores at the level of the whole brain
      and of individual regions. Our preliminary results indicate that the proposed
      voxel-based biomarkers are correlated with clinical outcomes.

PMID- 24443698
TI  - MODELING LONGITUDINAL MRI CHANGES IN POPULATIONS USING A LOCALIZED, INFORMATION
      THEORETIC MEASURE OF CONTRAST.
AB  - Longitudinal MR imaging during early brain development provides important
      information about growth patterns and the development of neurological disorders.
      We propose a new framework for studying brain growth patterns within and across
      populations based on MRI contrast changes, measured at each time point of
      interest and at each voxel. Our method uses regression in the LogOdds space and
      an information-theoretic measure of distance between distributions to capture
      contrast in a manner that is robust to imaging parameters and without requiring
      intensity normalization. We apply our method to a clinical neuroimaging study on
      early brain development in autism, where we obtain a 4D spatiotemporal model of
      contrast changes in multimodal structural MRI.

PMID- 24443699
TI  - SEMI-AUTOMATIC SEGMENTATION OF THE TONGUE FOR 3D MOTION ANALYSIS WITH DYNAMIC
      MRI.
AB  - Accurate segmentation is an important preprocessing step for measuring the
      internal deformation of the tongue during speech and swallowing using 3D dynamic
      MRI. In an MRI stack, manual segmentation of every 2D slice and time frame is
      time-consuming due to the large number of volumes captured over the entire task
      cycle. In this paper, we propose a semi-automatic segmentation workflow for
      processing 3D dynamic MRI of the tongue. The steps comprise seeding a few slices,
      seed propagation by deformable registration, random walker segmentation of the
      temporal stack of images and 3D super-resolution volumes. This method was
      validated on the tongue of two subjects carrying out the same speech task with
      multi-slice 2D dynamic cine-MR images obtained at three orthogonal orientations
      and 26 time frames. The resulting semi-automatic segmentations of 52 volumes
      showed an average dice similarity coefficient (DSC) score of 0.9 with reduced
      segmented volume variability compared to manual segmentations.

PMID- 24443701
TI  - Targeting new drugs with choline metabolism.

PMID- 24443700
TI  - Discovery of Novel Putative Inhibitors of UDP-GlcNAc 2-Epimerase as Potent
      Antibacterial Agents.
AB  - We present the discovery and optimization of a novel series of inhibitors of
      bacterial UDP-N-acetylglucosamine 2-epimerase (called 2-epimerase in this paper).
      Starting from virtual screening hits, the activity of various inhibitory
      molecules was optimized using a combination of structure-based and rational
      design approaches. We successfully designed and identified a 2-epimerase
      inhibitor (compound 12-ES-Na, that we named Epimerox) which blocked the growth of
      methicillin-resistant Staphylococcus aureus (MRSA) at 3.9 MUM MIC (minimum
      inhibitory concentration) and showed potent broad-range activity against all Gram
      positive bacteria that were tested. Additionally a microplate coupled assay was
      performed to further confirm that the 2-epimerase inhibition of Epimerox was
      through a target-specific mechanism. Furthermore, Epimerox demonstrated in vivo
      efficacy and had a pharmacokinetic profile that is consonant with it being
      developed into a promising new antibiotic agent for treatment of infections
      caused by Gram-positive bacteria.

PMID- 24443702
TI  - Pain Interference, Gambling Problem Severity, and Psychiatric Disorders among a
      Nationally Representative Sample of Adults.
AB  - BACKGROUND AND AIMS: A paucity of studies has examined the association between
      gambling and pain interference. We examined differences in the associations of
      gambling problem severity and psychiatric disorders among a nationally
      representative sample of adults with varying levels of pain interference.
      METHODS: Chi-square tests and logistic regression analyses were performed on
      National Epidemiologic Survey on Alcohol and Related Conditions data from 41,987
      adult respondents (48% men; 52% women), who were categorized according to two
      levels of pain interference (i.e., no or low pain interference [NLPI] or moderate
      or severe pain interference [MSPI]) and three levels of gambling problem severity
      (i.e., non-gamblers or low-frequency gamblers [NG], low-risk or at-risk gamblers
      [LRG], and problem or pathological gamblers [PPG]). RESULTS: MSPI respondents
      exhibited higher rates of PPG than NLPI respondents. Categories of Axis I
      disorders and clusters of mood, anxiety and substance-use disorders showed
      similarly strong associations with problem-gambling severity in MSPI and NLPI
      groups. Similarly strong associations between Axis II disorders (and each cluster
      - A, B and C) and problem-gambling severity were also observed in MSPI and NLPI
      groups. Exploratory analyses suggested potentially stronger relationships between
      PPG and dysthymia, panic disorder, and dependent personality disorder and LRG and
      specific phobia in NLPI compared to MSPI respondents. DISCUSSION AND CONCLUSIONS:
      While MSPI is associated with PPG, largely similar patterns of associations
      across pain-interference levels were observed between problem-gambling severity
      and Axis I and Axis II psychiatric disorders.

PMID- 24443703
TI  - Shaping Health Behavior across Generations: Evidence from Time Use data in the
      Panel Study of Income Dynamics and its Supplements.
AB  - This paper examines ways that families use time to shape their children's health
      behaviors. Specifically, it explores ways that parents can prepare children to
      make health-enhancing choices as adults. It also analyzes ways that offspring
      manage their time during young adulthood, when they are old enough to make
      independent decisions about whether they will spend their time producing health,
      as the Grossman model argues that individuals can do (Grossman 2000). The
      empirical research uses time diary data from the Child Development Supplement
      CDS), data from the Panel Study of Income Dynamics (PSID) core and the PSID's
      Transition to Adulthood (TA) module. By examining the intergenerational
      transmission of healthy behaviors, it is possible to better understand decisions
      individuals make in adulthood.

PMID- 24443704
TI  - Beyond the Protein Matrix: Probing Cofactor Variants in a Baeyer-Villiger
      Oxygenation Reaction.
AB  - A general question in biochemistry is the interplay between the chemical
      properties of cofactors and the surrounding protein matrix. Here, the functions
      of NADP+ and FAD are explored by investigation of a representative monooxygenase
      reconstituted with chemically-modified cofactor analogues. Like pieces of a
      jigsaw puzzle, the enzyme active site juxtaposes the flavin and nicotinamide
      rings, harnessing their H-bonding and steric properties to finely construct an
      oxygen-reacting center that restrains the flavin-peroxide intermediate in a
      catalytically-competent orientation. Strikingly, the regio- and
      stereoselectivities of the reaction are essentially unaffected by cofactor
      modifications. These observations indicate a remarkable robustness of this
      complex multi-cofactor active site, which has implications for enzyme design
      based on cofactor engineering approaches.

PMID- 24443705
TI  - Image versus Health: The Role of Perceptions of Masculinity on Sexual Risk
      Behaviors among HIV-Positive African American Men who have Sex with Men and
      Women.
AB  - BACKGROUND: HIV prevention has rarely explored the impact of childhood sexual
      abuse (CSA) across health domains among African American men who have sex with
      men and women (MSMW). Early sexual experiences may influence perceptions of
      gender roles, sexual identity, and risks for HIV/AIDS. The attribute of
      masculinity is commonly associated with strength and success. However, a legacy
      of racism and oppression may pose challenges for African American men in
      achieving gender-based milestones. Instead, proxies for success may include
      masculinity constructs with hypersexual posturing and prowess that contradict
      sexual health messages. METHODS: Two groups, each meeting twice for 90-minutes,
      of HIV-positive African American MSMW participated in discussions focusing on
      masculinity and sexual experiences. Participants were bisexual HIV-positive
      African American men who engaged in unprotected sex and had histories of CSA.
      Discussions were recorded, transcribed, and analyzed using consensual qualitative
      research and a constant comparison qualitative method. RESULTS: Participant mean
      age was 40.5 years (n=16). Majority had a high school education (69%), half were
      unemployed, and almost two-thirds earned less than $20,000 annually. Three
      themes, each with two subthemes, emerged that described the sociocultural context
      for engaging in high-risk sexual behaviors, and included: 1) the importance of
      inhabiting a "traditional" masculine gender role with: a) general and b) sexual
      masculine traits; 2) the influence of conceptions of masculinity on sexual
      identity with the associations: a) between being gay and being effeminate and b)
      between being gay and being HIV-positive, and; 3) CSA experiences with: a)
      appraisal of CSA and b) early sexual experiences as rites of passage. CONCLUSION:
      Attempts to be masculine may contribute to high-risk sexual behaviors. Research
      needs to explore how early sexual experiences shape perceptions of masculinity
      and masculinity's influence on receiving health messages for African American
      MSMW who may prioritize a specific image over sexual risk reduction.

PMID- 24443706
TI  - Effects of Docosahexaenoic Acid in Preventing Experimental Choroidal
      Neovascularization in Rodents.
AB  - BACKGROUND: The purpose of this study is to evaluate the effects of
      docosahexaenoic acid (DHA), a major omega-3-polyunsaturated fatty acid (omega-3
      PUFAs), in the development of experimental choroidal neovascularization (CNV) in
      rodents. METHODS: Experimental second generation Long Evans rats fed with diets
      of varying omega-3-PUFA content designed to produce significantly different
      retinal DHA levels were used in our studies. A transgenic mouse model (fat-1)
      engineered to over-produce DHA was also studied. CNV was induced by rupture of
      Bruch's membrane using laser photocoagulation. At 7 days after induction, animals
      were euthanatized, and eyes were collected. RPE/choroid flatmounts were labeled
      with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and
      high-performance 3D imaging software. RESULTS: The median of CNV complex volumes
      of animals with DHA-adequate diets was lower by 63% relative to that of animals
      with DHA-deficient diets. The median of CNV complex volumes in fat-1 transgenic
      mice was decreased by 59% relative to that of wild type controls. CONCLUSIONS:
      Dietary intake or genetic manipulation to increase the sources of DHA
      significantly diminished the volume of induced CNV lesions in rodents. They
      suggest that consumption of omega-3-PUFAs may serve to prevent CNV.

PMID- 24443707
TI  - Molecular Diagnosis of Helicobacter Pylori Strain by 16S rDNA PCR Amplification
      and Direct Sequencing.
AB  - AIM: Rapid detection of H.pylori strains by PCR-Sequencing. METHODS: 16S rDNA
      amplification by PCR from template genomic DNA, confirmation of amplicon size by
      agarose gel electrophoresis, sequencing of amplicons by automated sequencer,
      analysis of sequences by NCBI -BLAST software. RESULTS: The PCR -Sequencing and
      analysis of the sequence data by BLAST resulted in detection of the strain to be
      of H.pylori strain#26695. CONCLUSION: The pathogenicity of H.pylori depends on
      the strain of the bacteria, PCR-Sequencing and analysis of the sequence data by
      BLAST can be a very quick and useful diagnostic method of the pathogen.

PMID- 24443708
TI  - Developing Games for Health Behavior Change: Getting Started.
AB  - Many investigators are considering developing videogames for health (video-G4Hs)
      but have questions about how to get started. This report provides guidance for
      investigators considering a G4H as a behavioral intervention procedure from a
      team of experienced G4H developers. Thirteen commonly asked questions are
      answered, including defining a G4H, considerations in developing a team,
      considerations in G4H design, and anticipating unintended consequences.

PMID- 24443709
TI  - Exploring accurate Poisson-Boltzmann methods for biomolecular simulations.
AB  - Accurate and efficient treatment of electrostatics is a crucial step in
      computational analyses of biomolecular structures and dynamics. In this study, we
      have explored a second-order finite-difference numerical method to solve the
      widely used Poisson-Boltzmann equation for electrostatic analyses of realistic
      bio-molecules. The so-called immersed interface method was first validated and
      found to be consistent with the classical weighted harmonic averaging method for
      a diversified set of test biomolecules. The numerical accuracy and convergence
      behaviors of the new method were next analyzed in its computation of numerical
      reaction field grid potentials, energies, and atomic solvation forces. Overall
      similar convergence behaviors were observed as those by the classical method.
      Interestingly, the new method was found to deliver more accurate and better
      converged grid potentials than the classical method on or nearby the molecular
      surface, though the numerical advantage of the new method is reduced when grid
      potentials are extrapolated to the molecular surface. Our exploratory study
      indicates the need for further improving interpolation/extrapolation schemes in
      addition to the developments of higher-order numerical methods that have
      attracted most attention in the field.

PMID- 24443711
TI  - Occupational Lung Diseases among Soldiers Deployed to Iraq and Afghanistan.
AB  - Military personnel deployed to Iraq and Afghanistan, from 2004 to the present,
      has served in a setting of unique environmental conditions. Among these are
      exposures to burning trash in open air "burn pits" lit on fire with jet fuel JP
      8. Depending on trash burned--water bottles, styrofoam trays, medical waste,
      unexploded munitions, and computers--toxins may be released such as dioxins and n
      hexane and benzene. Particulate matter air pollution culminates from these fires
      and fumes. Additional environmental exposures entail sandstorms (Haboob, Shamal,
      and Sharqi) which differ in direction and relationship to rain. These wars saw
      the first use of improvised explosive devices (roadside phosphate bombs),as well
      as vehicle improvised explosive devices (car bombs), which not only potentially
      aerosolize metals, but also create shock waves to induce lung injury via blast
      overpressure. Conventional mortar rounds are also used by Al Qaeda in both Iraq
      and Afghanistan. Outdoor aeroallergens from date palm trees are prevalent in
      southern Iraq by the Tigris and Euphrates rivers, while indoor aeroallergen
      aspergillus predominates during the rainy season. High altitude lung disease may
      also compound the problem, particularly in Kandahar, Afghanistan. Clinically,
      soldiers may present with new-onset asthma or fixed airway obstruction. Some have
      constrictive bronchiolitis and vascular remodeling on open lung biopsy - despite
      having normal spirometry and chest xrays and CT scans of the chest. Others have
      been found to have titanium and other metals in the lung (rare in nature). Still
      others have fulminant biopsy-proven sarcoidiosis. We found DNA probe-positive
      Mycobacterium Avium Complex in lung from a soldier who had pneumonia, while
      serving near stagnant water and camels and goats outside Abu Gharib. This review
      highlights potential exposures, clinical syndromes, and the Denver Working Group
      recommendations on post-deployment health.

PMID- 24443710
TI  - Back to the future: recombinant polyclonal antibody therapeutics.
AB  - Antibody therapeutics are one of the fastest growing classes of pharmaceuticals,
      with an annual US market over $20 billion, developed to treat a variety of
      diseases including cancer, auto-immune and infectious diseases. Most are
      currently administered as a single molecule to treat a single disease, however
      there is mounting evidence that cocktails of multiple antibodies, each with a
      unique binding specificity and protective mechanism, may improve clinical
      efficacy. Here, we review progress in the development of oligoclonal combinations
      of antibodies to treat disease, focusing on identification of synergistic
      antibodies. We then discuss the application of modern antibody engineering
      technologies to produce highly potent antibody preparations, including
      oligoclonal antibody cocktails and truly recombinant polyclonal antibodies.
      Specific examples illustrating the synergy conferred by multiple antibodies will
      be provided for diseases caused by botulinum toxin, cancer and immune
      thrombocytopenia. The bioprocessing and regulatory options for these preparations
      will be discussed.

PMID- 24443712
TI  - The Hamilton Depression Scale--accelerator or break on antidepressant drug
      discovery?

PMID- 24443713
TI  - Introducing a 'neuropsychiatry' special issue: but what does that mean?

PMID- 24443715
TI  - Exogenous glucagon-like peptide 1 reduces contractions in human colon circular
      muscle.
AB  - Glucagon-like peptide 1 (GLP1) is a naturally occurring peptide secreted by
      intestinal L-cells. Though its primary function is to serve as an incretin, GLP1
      reduces gastrointestinal motility. However, only a handful of animal studies have
      specifically evaluated the influence of GLP1 on colonic motility. Consequently,
      the aims of this study were to investigate the effects induced by exogenous GLP1,
      to analyze the mechanism of action, and to verify the presence of GLP1 receptors
      (GLP1Rs) in human colon circular muscular strips. Organ bath technique, RT-PCR,
      western blotting, and immunofluorescence were used. In human colon, exogenous
      GLP1 reduced, in a concentration-dependent manner, the amplitude of the
      spontaneous contractions without affecting the frequency and the resting basal
      tone. This inhibitory effect was significantly reduced by exendin (9-39), a GLP1R
      antagonist, which per se significantly increased the spontaneous mechanical
      activity. Moreover, it was abolished by tetrodotoxin, a neural blocker, or Nomega
      nitro-l-arginine - a blocker of neuronal nitric oxide synthase (nNOS). The
      biomolecular analysis revealed a genic and protein expression of the GLP1R in the
      human colon. The double-labeling experiments with anti-neurofilament or anti-nNOS
      showed, for the first time, that immunoreactivity for the GLP1R was expressed in
      nitrergic neurons of the myenteric plexus. In conclusion, the results of this
      study suggest that GLP1R is expressed in the human colon and, once activated by
      exogenous GLP1, mediates an inhibitory effect on large intestine motility through
      NO neural release.

PMID- 24443716
TI  - Suppression of autophagic activation in the mouse uterus by estrogen and
      progesterone.
AB  - Autophagy is a major cellular catabolic pathway tightly associated with cell
      survival. The involvement of autophagy in the prolonged survival of blastocysts
      in the uterus is well established, and it was assumed that ovarian steroid
      hormones - progesterone (P4) and estrogens - have important roles in the
      regulation of autophagy. However, information is scarce regarding whether these
      hormones regulate autophagy in certain hormone-responsive cellular systems. In
      this study, we investigated the effects of estrogen and P4 on autophagic response
      in the uteri of pregnant mice and in ovariectomized (OVX) mice treated with
      hormones. During pregnancy, autophagic response is high on days 1 and 2 when the
      uterus shows an inflammatory response to mating, but it subsides around the time
      of implantation. Dexamethasone treatment to day 1 pregnant mice reduced autophagy
      in the uterus. In OVX mouse uteri, estrogen or P4 reduces autophagic response
      within 6 h. Glycogen content in OVX uteri was increased by 3-methyladenine
      treatment, suggesting that autophagy is involved in glycogen breakdown in the
      hormone-deprived uterus. The classical nuclear receptor antagonists, ICI 182 780
      or mifepristone, lead to the recovery of the autophagic response in OVX uteri.
      The suppression of autophagy by 17beta-estradiol is inversely correlated with the
      accumulation of phospho-mouse target of rapamycin, and rapamycin treatment is
      moderately effective in the upregulation of autophagic response in OVX mouse
      uteri. Collectively, this study establishes that the uterine autophagy is induced
      in hormone-derived environment and is suppressed by hormone treatment. Uterine
      autophagy may have multiple functions as a responsive mechanism to acute
      inflammation and as an energy provider by breaking down glycogen under hormone
      deprivation.

PMID- 24443717
TI  - Rapid profiling of enteric coated drug delivery spheres via broadband acoustic
      resonance dissolution spectroscopy (BARDS).
AB  - There is an increased trend towards the use of drug and enteric coated sugar
      spheres for controlled oral delivery of active pharmaceutical ingredients (API).
      This trend is driven by increased efficacy and ease of formulation of different
      dosage levels. However, difficulties exist in determining the thickness of drug
      and enteric coatings in a time efficient manner during manufacture, quality
      assurance and stability testing. The thickness of the coating determines the
      dosage of the API and the thickness of the enteric coating determines the release
      rate of the drug in the gastro-intestinal tract. Broadband Acoustic Resonance
      Dissolution Spectroscopy (BARDS) offers a rapid new approach to characterising
      the enteric coating thickness and the raw materials used in their manufacture.
      BARDS applications are based on reproducible changes in the compressibility of a
      solvent during dissolution which is monitored acoustically due to associated
      changes in the speed of sound in solution. It is demonstrated how core delivery
      sugar spheres have unique acoustic spectra attributable to the mean size
      distribution of the spheres. A steady state acoustic lag time is associated with
      the disintegration of the enteric coating, in basic solution. This lag time can
      be manipulated by varying the concentration of the base which affects the rate at
      which the coating dissolves. It is anticipated that the thickness/loading of the
      spheres can be estimated from the lag time. 

PMID- 24443714
TI  - Metabolic Dysfunction of Astrocyte: An Initiating Factor in Beta-amyloid
      Pathology?
AB  - Astrocytes, the most important energy regulator in the brain, support brain
      energy needs. In the meantime, numerous studies have demonstrated that impaired
      brain glucose metabolism is closely linked to abnormal astrocytic metabolism in
      AD. Indeed, the interaction between amyloid plaques and perturbed astrocytic
      homeostasis contributes to AD pathogenesis and astrocytic metabolic dysfunction
      is thought to be a trigger for Abeta pathology through oxidative stress and
      neuroinflammation Moreover, astrocytic metabolic dysfunction may regulate Abeta
      generation via modulating proteolytic processing of amyloid precursor protein
      (APP) by beta-secretase, gamma-secretase, and alpha-secretase, and may also
      modulate APP post-translational modifications such as glycosylation,
      phosphorylation, and tyrosine sulfation. While it is known that metabolic
      dysfunction of astrocytes contributes to the failure of Abeta clearance, it has
      also been reported that such dysfunction has neuroprotective property and
      exhibits no detrimental outcomes. Therefore, the exact role of astrocytic
      metabolic dysfunction in Abeta pathology remains to be further investigated.

PMID- 24443718
TI  - A lateral flow assay for identification of Escherichia coli by ribosomal RNA
      hybridisation.
AB  - Existing technologies for analysis of microbiological contaminants in food or
      clinical samples are often expensive and require laboratory settings and trained
      personnel. Here we present a lateral flow assay employing gold nanoparticle
      oligodeoxynucleotide conjugates and four-component sandwich hybridisation for
      direct detection of specific sequences in bacterial 16S ribosomal RNA. Combined
      with rapid "one step" lysis the developed procedure allows detection of 5 * 10(4)
      colony forming units per mL Escherichia coli within less than 25 minutes. Several
      Escherichia coli strains were detected successfully, whereas non-related as well
      as closely related bacterial species produced no signal. The developed nucleic
      acid lateral flow assay is inexpensive, rapid to perform and requires no nucleic
      acid amplification step. 

PMID- 24443719
TI  - Preparation and functionalization of a visible-light-excited europium complex
      modified luminescent protein for cell imaging applications.
AB  - Lanthanide complex-based luminescent bioprobes have shown great utility in a
      variety of time-resolved luminescence bioassays, but these bioprobes often
      require UV excitation and suffer from problems related to bioaffinity and
      biocompatibility for in vivo applications. In this work, a new visible-light
      excited europium(III) complex with the maximum excitation wavelength over 400 nm,
      BHHBB-Eu(3+)-BPT {BHHBB: 1,2-bis[4'-(1'',1'',1'',2'',2'',3'',3''-heptafluoro
      4'',6''-hexanedion-6''-yl)-benzyl]-benzene; BPT: 2-(N,N-diethylanilin-4-yl)-4,6
      bis(pyrazol-1-yl)-1,3,5-triazine}, has been synthesized for the preparation of an
      artificial luminescent protein that can be used as a visible-light-excited
      luminescent bioprobe for cell imaging. By encapsulating BHHBB-Eu(3+)-BPT into
      apoferritin with a simple dissociation-reassembly method, the luminescent
      protein, Eu@AFt, with a maximum excitation peak at 420 nm and a long luminescence
      lifetime of 365 MUs was fabricated and successfully used for visible-light
      excited time-resolved luminescence cell imaging. Moreover, by conjugating a
      mitochondria-targeting molecule, (5-N-succinimidoxy-5-oxopentyl)
      triphenylphosphonium bromide (SPTPP), onto the surface of Eu@AFt, a mitochondria
      specifically-tracking luminescent probe, Eu@AFt-SPTPP, was further prepared and
      used for visible-light-excited confocal luminescence microscopy imaging to
      visualize the mitochondria of living cells.

PMID- 24443720
TI  - Highly enhanced electrochemiluminescence based on pseudo triple-enzyme cascade
      catalysis and in situ generation of co-reactant for thrombin detection.
AB  - In this work, a novel pseudo triple-enzyme cascade catalysis amplification
      strategy was employed to fabricate a highly sensitive electrochemiluminescence
      (ECL) aptasensor for thrombin (TB) detection. The signal amplification of the
      proposed aptasensor was based on the synergistic catalysis of glucose
      dehydrogenase (GDH) and hemin/G-quadruplex to generate a co-reactant in situ for
      the ECL of peroxydisulfate. Gold nanorods (AuNRs) conjugated with GDH and hemin/G
      quadruplex were used as the secondary aptamer bioconjugate (TBA II) in this
      aptasensor. TB was sandwiched between TBA II and a thiol-terminated TB aptamer
      which self-assembled on the AuNRs-modified electrode. The pseudo triple-enzyme
      cascade catalysis was completed as follows: firstly, GDH could effectively
      catalyze the oxidation of glucose to gluconolactone, coupling with the reduction
      of beta-nicotinamide adenine dinucleotide hydrate (NAD(+)) into beta-nicotinamide
      adenine dinucleotide hydrogen (NADH). Then, the hemin/G-quadruplex acted as NADH
      oxidase, could rapidly oxidize NADH into NAD(+) accompanied with the generation
      of H2O2. Simultaneously, the hemin/G-quadruplex served as the horseradish
      peroxidase (HRP)-mimicking DNAzyme that further catalyzed the reduction of H2O2
      to generate O2in situ. Then the O2 produced acted as the co-reactant of
      peroxydisulfate, resulting in significant ECL signal amplification and highly
      sensitive ECL detection. The proposed aptasensor showed a wide linear range of
      0.0001-50 nM with a low detection limit of 33 fM (S/N = 3) for TB determination.
      The present work demonstrated that the novel strategy has great advantages of
      sensitivity, selectivity and reproducibility, which hold new promise for highly
      sensitive bioassays applied in clinical detection. 

PMID- 24443721
TI  - A mesofluidic platform integrating on-chip probe ultrasonication for multiple
      sample pretreatment involving denaturation, reduction, and digestion in protein
      identification assays by mass spectrometry.
AB  - The integration of ultrasound (US)-assisted sample processing on-chip in a lab-on
      a-valve (LOV) format for automated high-throughput shotgun proteomic assays is
      herein presented for the first time. The proof of concept of this system was
      demonstrated with the analysis of three proteins and sera from patients with
      lymphoma or myeloma. 

PMID- 24443722
TI  - Human plasma stability during handling and storage: impact on NMR metabolomics.
AB  - This work contributes to fill in some existing gaps in the knowledge of human
      plasma degradability during handling and storage, a paramount issue in Nuclear
      Magnetic Resonance (NMR) metabolomics. Regarding the comparison between heparin
      and EDTA anti-coagulant collection tubes, the former showed no interference of
      the polysaccharide, while conserving full spectral information. In relation to
      time/temperature conditions, room temperature was seen to have a large impact on
      lipoproteins and choline compounds from 2.5 hours. In addition, short-term
      storage at -20  degrees C was found suitable up to 7 days but, for periods up to
      1 month, -80  degrees C was recommended. Furthermore, in the case of reusing
      plasma samples, no more than 3 consecutive freeze-thaw cycles were found
      advisable. Finally, the impact of long-term -80  degrees C storage (up to 2.5
      years) was found almost negligible, as evaluated on a partially matched non
      fasting cohort (n = 49), after having investigated the possible confounding
      nature of the particular non-fasting conditions employed. 

PMID- 24443723
TI  - X-ray chemical imaging and the electronic structure of a single nanoplatelet
      Ni/graphene composite.
AB  - Chemical imaging and quantitative analysis of a single graphene nanoplatelet
      grown with Ni nanoparticles (Ni/graphene) has been performed by scanning
      transmission X-ray microscopy (STXM). Local electronic and chemical structure of
      Ni/graphene has been investigated by spatially resolved C, O K-edges and Ni L
      edge X-ray absorption near edge structure (XANES) spectroscopy, revealing the
      covalent anchoring of Ni(0) on graphene. This study facilitates the understanding
      of the structure modification of host materials for hydrogen storage and offers a
      better understanding of interaction between Ni particles and graphene. 

PMID- 24443724
TI  - New catalytic model systems of tyrosinase: fine tuning of the reactivity with
      pyrazole-based N-donor ligands.
AB  - Two new Cu(i) complexes have been synthesized and investigated as model systems
      of the enzyme tyrosinase. The corresponding ligands are based on a combination of
      an imine function with two different pyrazole groups. The reactivity of the
      prepared systems with respect to the conversion of monophenols to the
      corresponding ortho-quinones is investigated. The resulting data are compared to
      results obtained for other catalytic model systems of tyrosinase. 

PMID- 24443725
TI  - A porous coordination polymer with a reactive diiron paddlewheel unit.
AB  - A pillared-layer type porous coordination polymer containing a diiron paddlewheel
      unit has been synthesized and exhibits permanent porosity as confirmed by gas
      sorption analysis. 

PMID- 24443726
TI  - The long battle over payment for oncology services in the office setting.

PMID- 24443727
TI  - Policy and politics: a call for papers.

PMID- 24443728
TI  - Why oncologists should support single-payer national health insurance.

PMID- 24443729
TI  - Obamacare: why should we care?

PMID- 24443730
TI  - Where do patients with cancer in Iowa receive radiation therapy?
AB  - PURPOSE: Multiple studies have shown survival benefits in patients with cancer
      treated with radiation therapy, but access to treatment facilities has been found
      to limit its use. This study was undertaken to examine access issues in Iowa and
      determine a methodology for conducting a similar national analysis. PATIENTS AND
      METHODS: All Iowa residents who received radiation therapy regardless of where
      they were diagnosed or treated were identified through the Iowa Cancer Registry
      (ICR). Radiation oncologists were identified through the Iowa Physician
      Information System (IPIS). Radiation facilities were identified through IPIS and
      classified using the Commission on Cancer accreditation standard. RESULTS:
      Between 2004 and 2010, 113,885 invasive cancers in 106,603 patients, 28.5% of
      whom received radiation treatment, were entered in ICR. Mean and median travel
      times were 25.8 and 20.1 minutes, respectively, to the nearest facility but 42.4
      and 29.1 minutes, respectively, to the patient's chosen treatment facility.
      Multivariable analysis predicting travel time showed significant relationships
      for disease site, age, residence location, and facility category. Residents of
      small and isolated rural towns traveled nearly 3* longer than urban residents to
      receive radiation therapy, as did patients using certain categories of
      facilities. CONCLUSION: Half of Iowa patients could reach their nearest facility
      in 20 minutes, but instead, they traveled 30 minutes on average to receive
      treatment. The findings identified certain groups of patients with cancer who
      chose more distant facilities. However, other groups of patients with cancer,
      namely those residing in rural areas, had less choice, and some had to travel
      considerably farther to radiation facilities than urban patients.

PMID- 24443731
TI  - Access to chemotherapy services by availability of local and visiting
      oncologists.
AB  - PURPOSE: Geographic disparities have raised important questions about factors
      related to treatment choice and travel time, which can affect access to cancer
      care. PATIENTS AND METHODS: Iowa residents who received chemotherapy regardless
      of where they were diagnosed or treated were identified through the Iowa Cancer
      Registry (ICR), a member of the SEER program. Oncologists and their practice
      locations, including visiting consulting clinics (VCCs), were tracked through the
      Iowa Physician Information System. Oncologists, VCCs, and patients were mapped to
      hospital service areas (HSAs). RESULTS: Between 2004 and 2010, 113,885 newly
      diagnosed invasive cancers were entered into ICR; among patients in whom these
      cancers were diagnosed, 31.6% received chemotherapy as a first course of
      treatment. During this period, 106 Iowa oncologists practiced in 14 cities, and
      82 engaged in outreach to 85 VCCs in 77 rural communities. Of patients receiving
      chemotherapy, 63.0% resided in an HSA that had a local oncologist and traveled 21
      minutes for treatment on average. In contrast, 29.3% of patients receiving
      chemotherapy resided in an HSA with a VCC, and 7.7% resided in an HSA with no
      oncology provider. These latter two groups of patients traveled 58 minutes on
      average to receive chemotherapy. Availability of oncologists and VCCs affected
      where patients received chemotherapy. The establishment of VCCs increased access
      to oncologists in rural communities and increased the rate that chemotherapy was
      administered in rural communities from 10% to 24%, a notable increase in local
      access. CONCLUSION: Access to cancer care is dependent on the absolute number of
      providers, but it is also dependent on their geographic distribution.

PMID- 24443732
TI  - Enhancing the American Society of Clinical Oncology workforce information system
      with geographic distribution of oncologists and comparison of data sources for
      the number of practicing oncologists.
AB  - PURPOSE: The American Society of Clinical Oncology (ASCO) 2007 workforce report
      projected US oncologist shortages by 2020. Intervening years have witnessed
      shifting trends in both supply and demand, demonstrating the need to capture data
      in a dynamic manner. The ASCO Workforce Information System (WIS) provides an
      infrastructure to update annually emerging characteristics of US oncologists
      (medical oncologists, hematologist/oncologists, and hematologists). METHODS:
      Several possible data sources exist to capture the number of oncologists in the
      United States. The WIS primarily uses the American Medical Association Physician
      Masterfile database because it provides detailed demographics. This analysis also
      compares total counts of oncologists from American Board of Internal Medicine
      (ABIM) certification reports, the National Provider Identifier (NPI) database,
      and Medicare Physician Compare data. The analysis also examines geographic
      distribution of oncologists by age and US population data. RESULTS: For each of
      the data sources, we pulled 2013 data. The Masterfile identified 13,409
      oncologists. ABIM reported 13,757 oncologists. NPI listed 11,664 oncologists.
      Physician Compare identified 11,343 oncologists. Mapping of these data identifies
      distinct areas (primarily in central United States, Alaska, and Hawaii) that seem
      to lack ready access to oncologists. DISCUSSION: Efforts to survey oncologists
      about practice patterns will help determine if productivity and service delivery
      will change significantly. ASCO is committed to tracking oncologist supply and
      demand, as well as to providing timely analysis of strategies that will help
      address any shortages that may occur in specific regions or practice settings.

PMID- 24443733
TI  - Projected supply of and demand for oncologists and radiation oncologists through
      2025: an aging, better-insured population will result in shortage.
AB  - PURPOSE: The American Society of Clinical Oncology (ASCO) published a study in
      2007 that anticipated a shortage of oncologists by 2020. This study aims to
      update and better assess the market for chemotherapy and radiation therapy and
      the impact of health reform on capacity of and demand for oncologists and
      radiation oncologists. METHODS: The supply of oncologists and radiation
      oncologists, by age, sex, and specialty, was projected through 2025 with an input
      output model. The Medical Expenditure Panel Survey, commercial claims, and
      Medicare claims were analyzed to determine patterns of use by patient
      characteristics such as age, sex, health insurance coverage, cancer site,
      physician specialty, and service type. Patterns of use were then applied to the
      projected prevalence of cancer, using data from the SEER Program of the National
      Cancer Institute. RESULTS: Beginning in 2012, 16,347 oncologists and radiation
      oncologists were active and supplying 15,190 full-time equivalents (FTEs) of
      patient care. Without consideration of the Affordable Care Act (ACA), overall
      demand for oncologist services is projected to grow 40% (21,255 FTEs), whereas
      supply may grow only 25% (18,997 FTEs), generating a shortage of 2,258 FTEs in
      2025. When fully implemented, the ACA could increase the demand for oncologists
      and radiation oncologists by 500,000 visits per year, increasing the shortage to
      2,393 FTEs in 2025. CONCLUSION: Anticipated shortages are largely consistent with
      the projections of the ASCO 2007 workforce study but somewhat more delayed. The
      ACA may modestly exacerbate the shortage. Unless oncologist productivity can be
      enhanced, the anticipated shortage will strain the ability to provide quality
      cancer care.

PMID- 24443734
TI  - Help wanted!

PMID- 24443735
TI  - Opening the black box: the impact of an oncology management program consisting of
      level I pathways and an outbound nurse call system.
AB  - PURPOSE: The Innovent Oncology Program aims to improve the value of cancer care
      delivered to patients. McKesson Specialty Health and Texas Oncology (TXO)
      collaborated with Aetna to launch a pilot program. The study objectives were to
      evaluate the impact of Innovent on Level I Pathway compliance, implement the
      Patient Support Services program, and measure the rate and costs associated with
      chemotherapy-related emergency room (ER) visits and hospital admissions. PATIENTS
      AND METHODS: This was a prospective, nonrandomized evaluation of patients
      enrolled in Innovent from June 1, 2010, through May 31, 2012. Data from the
      iKnowMed electronic health record, the McKesson Specialty Health financial data
      warehouse, and Aetna claims data warehouse were analyzed. RESULTS: A total of 221
      patients were included and stratified according to disease and age groups; 76% of
      ordered regimens were on pathway; 24% were off pathway. Pathway adherence
      improved from TXO baseline adherence of 63%. Of the 221 patients, 81% enrolled in
      PSS. Within the breast, colorectal, and lung cancer groups, 14% and 24% of
      patients had an ER visit and in-patient admission (IPA; baseline) versus 10% and
      18% in Innovent, respectively; average in-patient days decreased from 2.1 to 1.2
      days, respectively. Total savings combined for the program was $506,481.
      CONCLUSION: Implementation of Innovent positively affected patient care in
      several ways: Fewer ER visits and IPAs occurred, in-patient days decreased,
      cancer-related use costs were reduced, and on-pathway adherence increased.

PMID- 24443736
TI  - Evaluating physician performance in oncology: moneyball becomes impactball.

PMID- 24443739
TI  - Commentary: Putting tools in context: how pediatric psychologists can leverage
      science to improve clinical care.

PMID- 24443741
TI  - Routh Early Career Award: From pediatric ninjutsu to pediatric psychology.

PMID- 24443743
TI  - Becoming a pediatric psychologist: a winding road from the 1970s to the present.
AB  - This article describes the career path of a pediatric psychologist over a 40 year
      period. This path developed in parallel with the development of pediatric
      psychology as a field. 

PMID- 24443742
TI  - Temperament, personality, and quality of life in pediatric cancer patients.
AB  - OBJECTIVE: The developmental psychology literature shows that children with
      higher levels of effortful control (EC) and ego-resilience (ER) display greater
      social competence and better emotional adjustment. This study examined whether
      these dispositional attributes contribute to positive quality of life (QOL) in
      pediatric cancer patients. METHOD: Participants were 103 pediatric cancer
      patients (and their parents) who were part of a larger parent study. At study
      entry, parents reported their own anxiety and depression and their children's EC
      and ER. At 3-month follow-up, parents reported children's QOL. RESULTS: ER was
      positively correlated with children's QOL. EC showed a positive indirect effect
      on QOL through ER. Inclusion of potential correlates of pediatric QOL (e.g.,
      parent neuroticism) did not change these relationships. CONCLUSIONS: Temperament
      and personality play significant roles in pediatric cancer patients' QOL.
      Assessing dispositional attributes early in treatment may help identify children
      at risk for poor QOL during and after treatment.

PMID- 24443744
TI  - Learning to ignore: a modeling study of a decremental cholinergic pathway and its
      influence on attention and learning.
AB  - Learning to ignore irrelevant stimuli is essential to achieving efficient and
      fluid attention, and serves as the complement to increasing attention to relevant
      stimuli. The different cholinergic (ACh) subsystems within the basal forebrain
      regulate attention in distinct but complementary ways. ACh projections from the
      substantia innominata/nucleus basalis region (SI/nBM) to the neocortex are
      necessary to increase attention to relevant stimuli and have been well studied.
      Lesser known are ACh projections from the medial septum/vertical limb of the
      diagonal band (MS/VDB) to the hippocampus and the cingulate that are necessary to
      reduce attention to irrelevant stimuli. We developed a neural simulation to
      provide insight into how ACh can decrement attention using this distinct pathway
      from the MS/VDB. We tested the model in behavioral paradigms that require
      decremental attention. The model exhibits behavioral effects such as associative
      learning, latent inhibition, and persisting behavior. Lesioning the MS/VDB
      disrupts latent inhibition, and drastically increases perseverative behavior.
      Taken together, the model demonstrates that the ACh decremental pathway is
      necessary for appropriate learning and attention under dynamic circumstances and
      suggests a canonical neural architecture for decrementing attention.

PMID- 24443747
TI  - Good medicine: high volume neuter clinic a ray of hope on American Indian
      reservation.

PMID- 24443745
TI  - AMPK agonist AICAR improves cognition and motor coordination in young and aged
      mice.
AB  - Normal aging can result in a decline of memory and muscle function. Exercise may
      prevent or delay these changes. However, aging-associated frailty can preclude
      physical activity. In young sedentary animals, pharmacological activation of AMP
      activated protein kinase (AMPK), a transcriptional regulator important for muscle
      physiology, enhanced spatial memory function, and endurance. In the present study
      we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside
      (AICAR) on memory and motor function in young (5- to 7-wk-old) and aged (23-mo
      old) female C57Bl/6 mice, and in young (4- to 6-wk-old) transgenic mice with
      muscle-specific mutated AMPK alpha2-subunit (AMPK-DN). Mice were injected with
      AICAR (500 mg/kg) for 3-14 d. Two weeks thereafter animals were tested in the
      Morris water maze, rotarod, and open field. Improved water maze performance and
      motor function were observed, albeit at longer duration of administration, in
      aged (14-d AICAR) than in young (3-d AICAR) mice. In the AMPK-DN mice, the
      compound did not enhance behavior, providing support for a muscle-mediated
      mechanism. In addition, microarray analysis of muscle and hippocampal tissue
      derived from aged mice treated with AICAR revealed changes in gene expression in
      both tissues, which correlated with behavioral effects in a dose-dependent
      manner. Pronounced up-regulation of mitochondrial genes in muscle was observed.
      In the hippocampus, genes relevant to neuronal development and plasticity were
      enriched. Altogether, endurance-related factors may mediate both muscle and brain
      health in aging, and could play a role in new therapeutic interventions. 

PMID- 24443748
TI  - AVMF puts mission into action: five educational events reach out to public.

PMID- 24443749
TI  - AVMA gives testimony at hearing on soring.

PMID- 24443750
TI  - Proposal would cease accreditation of foreign schools.

PMID- 24443751
TI  - Navigating a sea of technology: taking a quick look at online resources for
      veterinarians.

PMID- 24443746
TI  - Targeted peptide measurements in biology and medicine: best practices for mass
      spectrometry-based assay development using a fit-for-purpose approach.
AB  - Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction
      monitoring (MRM) to study biological and biomedical questions is well underway in
      the proteomics community. Successful application depends on the ability to
      generate reliable assays that uniquely and confidently identify target peptides
      in a sample. Unfortunately, there is a wide range of criteria being applied to
      say that an assay has been successfully developed. There is no consensus on what
      criteria are acceptable and little understanding of the impact of variable
      criteria on the quality of the results generated. Publications describing
      targeted MS assays for peptides frequently do not contain sufficient information
      for readers to establish confidence that the tests work as intended or to be able
      to apply the tests described in their own labs. Guidance must be developed so
      that targeted MS assays with established performance can be made widely
      distributed and applied by many labs worldwide. To begin to address the problems
      and their solutions, a workshop was held at the National Institutes of Health
      with representatives from the multiple communities developing and employing
      targeted MS assays. Participants discussed the analytical goals of their
      experiments and the experimental evidence needed to establish that the assays
      they develop work as intended and are achieving the required levels of
      performance. Using this "fit-for-purpose" approach, the group defined three tiers
      of assays distinguished by their performance and extent of analytical
      characterization. Computational and statistical tools useful for the analysis of
      targeted MS results were described. Participants also detailed the information
      that authors need to provide in their manuscripts to enable reviewers and readers
      to clearly understand what procedures were performed and to evaluate the
      reliability of the peptide or protein quantification measurements reported. This
      paper presents a summary of the meeting and recommendations. 

PMID- 24443752
TI  - USDA awards $4 million for veterinarians in shortage areas.

PMID- 24443753
TI  - FDA wants help fighting drug-resistant parasites.

PMID- 24443754
TI  - Eliminating dog-transmitted rabies: end of human deaths in Americas from dog
      transmitted rabies targeted for 2015.

PMID- 24443755
TI  - Advocates' video targets farm of pork producers' president.

PMID- 24443756
TI  - Call for antimicrobial stewardship policy.

PMID- 24443757
TI  - Methods in a study of cranial cruciate ligament disease in dogs.

PMID- 24443758
TI  - The authors respond.

PMID- 24443759
TI  - AVMA governance changes.

PMID- 24443760
TI  - AVMA governance changes.

PMID- 24443761
TI  - Urethral obstruction and age of cats.

PMID- 24443762
TI  - Veterinary education and the profession's future.

PMID- 24443763
TI  - Equality of opportunity in veterinary medicine.

PMID- 24443764
TI  - Broadening our veterinary clientele.

PMID- 24443765
TI  - Medicaid program; state plan home and community-based services, 5-year period for
      waivers, provider payment reassignment, and home and community-based setting
      requirements for Community First Choice and home and community-based services
      (HCBS) waivers. Final rule.
AB  - This final rule amends the Medicaid regulations to define and describe state plan
      section 1915(i) home and community-based services (HCBS) under the Social
      Security Act (the Act) amended by the Affordable Care Act. This rule offers
      states new flexibilities in providing necessary and appropriate services to
      elderly and disabled populations. This rule describes Medicaid coverage of the
      optional state plan benefit to furnish home and community based-services and draw
      federal matching funds. This rule also provides for a 5-year duration for certain
      demonstration projects or waivers at the discretion of the Secretary, when they
      provide medical assistance for individuals dually eligible for Medicaid and
      Medicare benefits, includes payment reassignment provisions because state
      Medicaid programs often operate as the primary or only payer for the class of
      practitioners that includes HCBS providers, and amends Medicaid regulations to
      provide home and community-based setting requirements related to the Affordable
      Care Act for Community First Choice State plan option. This final rule also makes
      several important changes to the regulations implementing Medicaid 1915(c) HCBS
      waivers.

PMID- 24443766
TI  - Effective date of requirement for premarket approval for transilluminator for
      breast evaluation and sorbent hemoperfusion system (SHS) devices for the
      treatment of hepatic coma and metabolic disturbances; reclassification of SHS and
      devices for the treatment of poisoning and drug overdose. Final order.
AB  - The Food and Drug Administration (FDA) is issuing a final order to require the
      filing of a premarket approval application (PMA) for the transilluminator for
      breast evaluation and sorbent hemoperfusion system (SHS) devices for the
      treatment of hepatic coma and metabolic disturbances and to reclassify SHS
      devices for the treatment of poisoning and drug overdose, a preamendments class
      III device, into class II (special controls).

PMID- 24443767
TI  - Maternal use of 5-aminosalicylates in early pregnancy and congenital malformation
      risk in the offspring.
AB  - OBJECTIVE: Most previous studies have failed to demonstrate any effect of
      maternal use of 5-aminosalicylates (5-ASA) on malformation risk, but the number
      of infants studied have, in most cases, been low. The objective of the study was
      to get data from a large study with prospectively ascertained exposure
      information. MATERIAL AND METHODS: The study was based on data in the Swedish
      Medical Birth Register (1996-2011) where identification of maternal drug use is
      made from midwife interviews in early pregnancy. The presence of congenital
      malformations was ascertained from three national registers. Adjusted odds ratios
      were calculated by the Mantel-Haenszel methodology. RESULTS: Among 1,552,109
      women, 3651 with 3721 infants had reported the use of 5-ASAs in early pregnancy.
      The risk of a major malformation was increased (1.37, 95% confidence interval =
      1.17-1.62) and still more for a cardiovascular defect (1.74, 1.37-2.22). This
      effect seemed to be influenced by concomitant use of systemic
      glucocorticosteroids or immunosuppressants but some confounding by indication may
      also exist. There was no marked difference between the four 5-ASA drugs studied.
      CONCLUSIONS: Infants born of women who use 5-ASA drugs in early pregnancy have an
      increased risk of a congenital malformation, notably a cardiovascular defect.
      This could be a drug effect or an effect of an active inflammatory bowel disease.

PMID- 24443769
TI  - Assembly of acid-functionalized single-walled carbon nanotubes at oil/water
      interfaces.
AB  - The efficient segregation of water-soluble, acid-functionalized, single-walled
      carbon nanotubes (SWCNTs) at the oil/water interface was induced by dissolving
      low-molecular-weight amine-terminated polystyrene (PS-NH2) in the oil phase. Salt
      bridge interactions between carboxylic acid groups of SWCNTs and amine groups of
      PS drove the assembly of SWCNTs at the interface, monitored by pendant drop
      tensiometry and laser scanning confocal microscopy. The impact of PS end-group
      functionality, PS and SWCNT concentrations, and the degree of SWCNT acid
      modification on the interfacial activity was assessed, and a sharp drop in
      interfacial tension was observed above a critical SWCNT concentration.
      Interfacial tensions were low enough to support stable oil/water emulsions.
      Further experiments, including potentiometric titrations and the replacement of
      SWCNTs by other carboxyl-containing species, demonstrated that the interfacial
      tension drop reflects the loss of SWCNT charge as the pH falls near/below the
      intrinsic carboxyl dissociation constant; species lacking multivalent carboxylic
      acid groups are inactive. The trapped SWCNTs appear to be neither ordered nor
      oriented. 

PMID- 24443768
TI  - Posttraumatic growth in parents and pediatric patients.
AB  - BACKGROUND: Pediatric medical experiences are potentially traumatic but may lead
      to psychological growth. OBJECTIVE: The study objective was to synthesize the
      published literature regarding posttraumatic growth (PTG) in parents and patients
      with serious pediatric illness (SPI) into a conceptual model. METHODS: We
      systematically searched MEDLINE, CINAHL, PsychInfo, and Sociological Abstracts in
      December 2012 to identify articles on stress or trauma caused by medical events
      with PTG as an outcome, reviewing articles pertaining to the pediatric
      population. We additionally reviewed articles outside pediatric medicine that
      described a model of PTG. RESULTS: Of the 605 articles identified, 55 met
      inclusion criteria, 26 of which examined parents or pediatric patients. Parents
      and children may experience PTG following medical trauma through a combination of
      cognitive and affective processing of their subjective experience. Components of
      SPI-PTG are unclear, but may include greater appreciation of life, improved
      interpersonal relationships, greater personal strength, recognition of new
      possibilities in one's life course, spiritual or religious growth, and
      reconstruction of a positive body image. Individual characteristics, and the
      level of social support, may affect the likelihood that SPI-PTG will occur. SPI
      PTG in siblings and other family members has not been well studied. CONCLUSIONS:
      SPI-PTG is an important but understudied and inadequately understood phenomenon
      affecting children with SPI and their family members. Research should focus on
      clarifying SPI-PTG domains, creating measurement instruments, assessing SPI-PTG
      across the pediatric age range and among family members, and improving our
      understanding of and ability to positively intervene regarding the cognitive
      processes of rumination, sense making, and benefit finding.

PMID- 24443770
TI  - Preliminary testing for endometriosis and gene polymorphisms.

PMID- 24443771
TI  - Saponins: a renewable and biodegradable surfactant from its microwave-assisted
      extraction to the synthesis of monodisperse lattices.
AB  - Synthetic surfactants are widely used in emulsion polymerization, but it is
      increasingly desirable to replace them with naturally derived molecules with a
      reduced environmental burden. This study demonstrates the use of saponins as
      biodegradable and renewable surfactants for emulsion polymerization. This
      chemical has been extracted from soapnuts by microwave assisted extraction and
      characterized in terms of surfactant properties prior to emulsion polymerization.
      The results in terms of particle size distribution and morphology control have
      been compared to those obtained with classical nonionic (NP40) or anionic (SDS)
      industrial surfactants. Microwave-extracted saponins were able to lead to latexes
      as stable as standard PS latex, as shown by the CMC and CCC measurements. The
      saponin-stabilized PS particles have been characterized in terms of particle size
      and distribution by Dynamic Light Scattering and Asymmetrical Flow Field Flow
      Fractionation. Monomodal and monodispersed particles ranging from 250 to 480 nm
      in terms of diameter with a particle size distribution below 1.03 have been
      synthesized. 

PMID- 24443772
TI  - Si-Mn/reduced graphene oxide nanocomposite anodes with enhanced capacity and
      stability for lithium-ion batteries.
AB  - Although Si is a promising high-capacity anode material for Li-ion batteries
      (LIB), it suffers from capacity fading due to excessively large volumetric
      changes upon Li insertion. Nanocarbon materials have been used to enhance the
      cyclic stability of LIB anodes, but they have an inherently low specific
      capacity. To address these issues, we present a novel ternary nanocomposite of
      Si, Mn, and reduced graphene oxide (rGO) for LIB anodes, in which the Si-Mn alloy
      offers high capacity characteristics and embedded rGO nanosheets confer
      structural stability. Si-Mn/rGO ternary nanocomposites were synthesized by
      mechanical complexation and subsequent thermal reduction of mixtures of Si
      nanoparticles, MnO2 nanorods, and rGO nanosheets. Resulting ternary nanocomposite
      anodes displayed a specific capacity of 600 mAh/g with ~90% capacity retention
      after 50 cycles at a current density of 100 mA/g. The enhanced performance is
      attributed to facilitated Li-ion reactions with the MnSi alloy phase and the
      formation of a structurally reinforced electroconductive matrix of rGO
      nanosheets. The ternary nanocomposite design paradigm presented in this study can
      be exploited for the development of high-capacity and long-life anode materials
      for versatile LIB applications. 

PMID- 24443773
TI  - Free skin flap reconstruction after partial hypopharyngectomy with laryngeal
      preservation.
AB  - Surgical resection of hypopharyngeal cancer often affects laryngeal function. The
      aim of this study is to assess the reliability and efficacy of free skin flap
      transfer after partial hypopharyngectomy with laryngeal preservation. This study
      designs a retrospective analysis. The subjects were 54 patients who underwent
      free skin flap reconstruction immediately after partial pharyngolaryngectomy or
      hypopharyngectomy with laryngeal preservation. The defects were classified into
      four types based on the location of the hypopharyngeal defect. Functional results
      were evaluated by routine physical examination findings and parameters related to
      swallowing function and X-ray barium deglutition examination. Perioperative
      mortalities and morbidities were reviewed. There were no perioperative
      mortalities and 98% of the flaps survived. Forty-three patients (80%) were able
      to eat an unrestricted diet and experienced no aspiration. Restriction of the
      diet was significantly associated with the extent of oesophageal mucosal
      resection. In conclusion, free skin flap reconstruction is confirmed to be a safe
      and effective strategy to maintain laryngeal function and good quality-of-life.

PMID- 24443774
TI  - Effect of BMI on modality-specific outcomes in immediate breast reconstruction
      (IBR)--a propensity-matched analysis using the 2005-2011 ACS-NSQIP datasets.
AB  - Obesity is a prevalent, multisystem disease emerging as a pervasive risk factor
      for surgical morbidity. This study aims to perform a modality-specific risk
      assessment of IBR outcomes using the World Health Organisation (WHO) obesity
      stratification. This study reviewed the 2005-2011 ACS-NSQIP databases,
      identifying encounters for either implant or autologous-based reconstruction.
      Patients were classified and compared based on WHO classification criteria for
      BMI, and complications were divided into any surgical, major surgical, wound, and
      medical complications. A total of 18,194 patients underwent IBR. Patients were
      Caucasian (76.1%) and middle aged (45-64 years) (62.4%), with an average BMI of
      27.1 +/- 6.3 kg/m(2). A total of 14,585 patients underwent implant-based
      reconstructions. A multivariate logistic regression analysis of patient
      characteristics associated with autologous reconstruction revealed several
      independently associated factors, summarised in Table III. Our analysis revealed
      that reconstructive modality was not statistically associated with surgical
      morbidity in class I obese patients (OR = 1.21, p = 0.328), but was independently
      associated with progressively greater odds of surgical complications in class II
      (OR = 1.92, CI = 1.04-3.55, p = 0.036) and class III (OR = 2.71, CI = 1.14-6.46,
      p = 0.024). This study characterises the modality-specific risk of surgical and
      medical morbidity in patients undergoing IBR across BMI-stratified cohorts. The
      risk-adjusted models of early morbidity in IBR reveal a significant BMI-specific
      risk divergence that occurs at class II obesity cohorts and above. These data
      serve as a useful benchmark for early, modality-specific morbidity across BMI
      stratified cohorts and can be used to better tailor preoperative risk counselling
      in patients considering autologous reconstructions.

PMID- 24443775
TI  - Fluorination of epitaxial oxides: synthesis of perovskite oxyfluoride thin films.
AB  - While the synthesis of ABO3 perovskite films has enabled new strategies to
      control the functionality of this material class, the chemistries that have been
      realized in thin film form constitute only a fraction of those accessible to bulk
      chemists. Here, we report the synthesis of oxyfluoride films, where the
      incorporation of F may provide a new means to tune physical properties in thin
      films by modifying electronic structure. Fluorination is achieved by spin coating
      a poly(vinylidene fluoride) (PVDF) solution onto oxygen-deficient films. The
      film/polymer bilayer is then annealed, promoting the diffusion of F into the
      film. We have used this method to synthesize SrFeO(3-alpha)Fgamma films, as
      confirmed by X-ray photoemission spectroscopy and X-ray absorption spectroscopy.

PMID- 24443776
TI  - The co-use of tobacco and cannabis among adolescents over a 30-year period.
AB  - BACKGROUND: This study explores the patterns of use and co-use of tobacco and
      cannabis among Ontario adolescents over 3 decades and if characteristics of co
      users and single substance users have changed. METHODS: Co-use trends for 1981
      2011 were analyzed using the Centre for Addiction and Mental Health Ontario
      Student Drug Use and Health Survey, which includes 38,331 students in grades 7,
      9, and 11. A co-user was defined as someone reporting daily tobacco and/or
      cannabis use in the past month. Trends over time (by gender and academic
      performance) were analyzed with logistic regression. RESULTS: The prevalence of
      tobacco-only use, cannabis-only use, and co-use fluctuated considerably. During
      1981-1993, there were more tobacco-only users than co-users and cannabis-only
      users; since 1993 the prevalence of tobacco use has decreased dramatically. Co
      use prevalence peaked at 12% (95% confidence interval: 9, 15) in 1999, when
      prevalence of overall use of both substances was highest. In 2011, 92% of tobacco
      users also used cannabis, up from 16% in 1991. CONCLUSIONS: In 2011 nearly all
      students who smoke tobacco daily also use cannabis. Non-regular use of either
      substance is highest now compared with the past 3 decades. Contemporary tobacco
      and cannabis co-users are significantly different than past users. Youth
      prevention programs should understand the changing context of cannabis and
      tobacco among youth.

PMID- 24443777
TI  - Medications at school: disposing of pharmaceutical waste.
AB  - BACKGROUND: This project quantified and categorized medications left unclaimed by
      students at the end of the school year. It determined the feasibility of a model
      medication disposal program and assessed school nurses' perceptions of
      environmentally responsible medication disposal. METHODS: At a large urban school
      district all unclaimed medications were collected at the end of a school year to
      determine the extent and nature of this problem. Nurses documented unclaimed
      medications and transported them to a central district location. An
      environmentally responsible medication disposal program, consisting of sealed
      containers bound for a local hospital's disposal system, was implemented.
      RESULTS: In a school district of approximately 133,000 students, there were 926
      different medications abandoned at the end of a school year brought to a central
      disposal area. Nurses complied with the newly implemented protocol. Information
      collected from nurses indicates acceptance of the program. Disposal of unclaimed
      medications at a central location, use of secured containers, and transportation
      to a hospital for environmentally responsible disposal proved to be feasible and
      acceptable to the staff. CONCLUSIONS: Unclaimed medications at school each year
      pose a potentially huge environmental risk when disposed of improperly. It is
      feasible to implement an environmentally responsible medication disposal protocol
      at schools.

PMID- 24443778
TI  - Sugar-sweetened beverage consumption among a subset of Canadian youth.
AB  - BACKGROUND: Sugar-sweetened beverages (SSBs) may play a role in increased rates
      of obesity. This study examined patterns and frequencies of beverage consumption
      among youth in 3 distinct regions in Canada, and examined associations between
      beverage consumption and age, sex, body mass index (BMI), physical activity and
      dieting behavior, as well as beverage displacement. METHODS: The study included
      data from 10,188 youth (ages 13-18) from Hamilton and Thunder Bay, Ontario, and
      Prince Edward Island (PEI) in 2009 to 2010. The study used in-school self
      reported surveys with 12 questions regarding beverage consumption during the
      previous day, along with self-reported height, weight, physical activity levels,
      and demographic information. Logistic regression analyses were conducted to
      examine variables associated with SSB intake. RESULTS: Overall, 80% of youth
      consumed at least 1 SSB in the previous day, with 44% consuming 3 or more SSBs.
      Youth in Thunder Bay consumed significantly more SSBs than Hamilton and PEI, and
      youth in Hamilton consumed more SSBs than PEI. Boys consumed significantly more
      SSBs than girls. Older and more physically active youth consumed significantly
      fewer SSBs. No significant association between BMI and SSB consumption was
      observed in any model. A modest positive correlation was identified between SSB
      consumption and milk (r = .06, p < .001) and 100% fruit juice (r = .10, p <
      .001). CONCLUSIONS: A large proportion of youth consumed SSBs, many at high
      levels. Research evaluating SSB policy and interventions should be considered a
      priority.

PMID- 24443779
TI  - Piloting "sodabriety": a school-based intervention to impact sugar-sweetened
      beverage consumption in rural Appalachian high schools.
AB  - BACKGROUND: Sugar-sweetened beverages (SSBs) are the largest source of added
      sugar in the US diet. In adolescents aged 12-19, these drinks account for 13% to
      28% of total daily calories. Compared with other adolescents, those residing in
      Appalachia have the highest consumption rates of SSBs. METHODS: Using a Teen
      Advisory Council (TAC), a student-designed and student-led intervention was
      conducted at 2 high schools in a rural Appalachian county. Using repeated
      measures models design with Bonferroni correction, data were collected on daily
      and weekly consumption of SSBs and of water at baseline, immediately post
      intervention, and 30 days post-intervention. Vending machine surveys were
      completed. RESULTS: The 186 participants reported purchasing SSBs from school
      vending machines (41.4%), cafeteria (36.5%), and school stores (7.7%). Daily SSB
      servings decreased from an average of 2.32 (SD = 2.14) to 1.32 (SD = 1.29) (p <
      .001). Weekly consumption decreased from an average of 4.30 (SD = 2.40) days/week
      to 2.64 (SD = 1.91) (p < .001). Water consumption increased 19% from baseline to
      immediately post-intervention. CONCLUSIONS: Student-directed efforts to support
      behavioral change are feasible and effective at affecting individual lifestyle
      behaviors. Small and manageable changes may lead to net improvements in lifestyle
      behaviors.

PMID- 24443780
TI  - What proportion of preschool-aged children consume sweetened beverages?
AB  - BACKGROUND: Obesity affects nearly 17% of US children and youth 2-19 years old
      and 10% of infants and toddlers under the age of 2 years. One strategy for
      addressing obesity is to discourage sugar-sweetened beverage (SSB) consumption.
      Compared with their older school-aged counterparts, children <= 5 years depend
      largely on parents for the purchase and serving of SSBs. Therefore, recognizing
      parental factors associated with children's intake of SSBs is important. METHODS:
      This study used cross-sectional data from parents of children <= 5 years old to
      examine SSB consumption and associated factors. Elements of the Health Belief
      Model and Theory of Reasoned Action facilitated data analysis and interpretation.
      RESULTS: The most consistent predictor of SSB intake was child age. Nearly 94% of
      children aged 3-5 years consumed sweetened milk products, 88% consumed fruity
      drinks, 63% consumed sodas, and 56% consumed sports drinks and sweet tea.
      Adjusting for all other factors, the only parental psychosocial factor associated
      with SSB intake was self-efficacy (predicting fruity drinks consumption).
      CONCLUSIONS: More children drink SSBs as they get older. Interventions designed
      to prevent SSB consumption should occur early, before children reach preschool
      age. Additional study of parental factors influencing SSB intake in early
      childhood is recommended.

PMID- 24443781
TI  - Perceptions of tap water and school water fountains and association with intake
      of plain water and sugar-sweetened beverages.
AB  - BACKGROUND: Little is known regarding youth perceptions of tap water and school
      water fountains and how these relate to water and sugar-sweetened beverage (SSB)
      intake. METHODS: We used national 2010 YouthStyles data to assess perceptions of
      tap water and school water fountains and associations with water and SSB intake.
      RESULTS: Nearly 1 in 5 participants disagreed their tap water was safe and nearly
      2 in 5 disagreed school water fountains were clean and safe. Perceived tap water
      risk was more prevalent among non-Hispanic (NH) Blacks (26.4%) and Hispanics
      (28.3%) compared with NH Whites (14.7%, p < .001) and more prevalent among lower
      income youth. Negative water fountain perceptions were more common among high
      school-aged youth. Perceived tap water risk was not associated with SSB intake
      (odds ratio [OR] = 1.0, 95% confidence interval [CI]: 0.6, 1.5) or water intake
      (OR = 1.4, 95% CI: 0.9, 2.1). Negative water fountain perceptions were associated
      with SSB intake only among Hispanics (race/ethnicity interaction p < .001; OR =
      2.9, 95% CI: 1.3, 6.6) but were not associated with water intake. CONCLUSION:
      Negative perceptions of tap water and water fountains among youth are common and
      should be considered in efforts to provide water in schools.

PMID- 24443782
TI  - Elementary and middle school children's acceptance of lower calorie flavored milk
      as measured by milk shipment and participation in the National School Lunch
      Program.
AB  - BACKGROUND: The United States Department of Agriculture's (USDA) new nutrition
      standards for school meals include sweeping changes setting upper limits on
      calories served and limit milk offerings to low fat or fat-free and, if flavored,
      only fat-free. Milk processors are lowering the calories in flavored milks. As
      changes to milk impact school lunch participation and milk consumption, it is
      important to know the impact of these modifications. METHODS: Elementary and
      middle schools from 17 public school districts that changed from standard
      flavored milk (160-180 kcal/8 oz) to lower calorie flavored milk (140-150 kcal/8
      oz) between 2008 and 2009 were enrolled. Milk shipment and National School Lunch
      Program (NSLP) participation rates were collected for 3 time periods over 12
      months (pre-reformulation, at the time of reformulation, and after
      reformulation). Linear mixed models were used with adjustments for free/reduced
      meal eligibility. RESULTS: No changes were seen in shipment of flavored milk or
      all milk, including unflavored. The NSLP participation rates dropped when lower
      calorie flavored milk was first offered, but recovered over time. CONCLUSIONS:
      While school children appear to accept lower calorie flavored milk, further
      monitoring is warranted as most of the flavored milks offered were not fat-free
      as was required by USDA as of fall 2012.

PMID- 24443783
TI  - A food service intervention improves whole grain access at lunch in rural
      elementary schools.
AB  - BACKGROUND: Whole grain (WG) options are often limited in schools, which may
      impact rural, low-income students who rely on school meals for a substantial
      portion of their food intake. This study examined the changes in the availability
      and quantity of WG and refined grain foods offered in schools participating in
      the Creating Healthy, Active and Nurturing Growing-up Environments (CHANGE)
      study, a randomized, controlled intervention among rural communities (4
      intervention and 4 control). METHODS: Foods were assessed using production
      records, recipes, and nutrition labels from breakfast and lunch over 1 week
      during fall 2008 and spring 2009. Key informant interviews were conducted with
      school food service directors in the spring 2009. RESULTS: The CHANGE
      intervention schools significantly increased the average percent of school days
      WGs were offered (p = .047) and the amount of WGs offered/food item (ounces) at
      lunch compared with control schools (p = .02). There was a significant decrease
      in the percent of students with access to refined grains at lunch compared with
      control schools (p = .049), although there were no significant differences in WG
      availability during breakfast. CONCLUSIONS: The CHANGE schools improved WG
      availability, enabling student's WG consumption to be closer to national
      recommendations.

PMID- 24443784
TI  - Antimicrobial activity of Metschnikowia pulcherrima on wine yeasts.
AB  - AIMS: In the present study, it was investigated the antagonistic behaviour of
      Metschnikowia pulcherrima, as biocontrol agent, against the main wine yeast
      species involved in the winemaking process. METHODS AND RESULTS: Seven strains of
      M. pulcherrima were evaluated for the antimicrobial activity against 114 yeast
      strains belonging to Pichia, Candida, Hanseniaspora, Kluyveromyces,
      Saccharomycodes, Torulaspora, Brettanomyces and Saccharomyces genera. Results
      showed both different inter-generic and intra-generic responses to the
      antimicrobial action of M. pulcherrima strains. Interestingly, the antimicrobial
      activity of M. pulcherrima did not have any influence on the growth of
      Saccharomyces cerevisiae. Instead, M. pulcherrima displayed a broad and effective
      antimicrobial action on undesired wild spoilage yeasts, such as
      Brettanomyces/Dekkera, Hanseniaspora and Pichia genera. Fermentation trials
      carried out in synthetic grape must confirmed the antimicrobial activity of M.
      pulcherrima, determining the early death of the non-Saccharomyces co-inoculated
      cultures. CONCLUSIONS: The antimicrobial activity of M. pulcherrima does not seem
      due to proteinaceous compounds such as killer phenomenon, but to the
      pulcherriminic acid (the precursor of pulcherrimin pigment) that depletes iron
      present in the medium, making it not available to the other yeasts. SIGNIFICANCE
      AND IMPACT OF THE STUDY: These data agree with and further support the potential
      use of selected M. pulcherrima strains in controlled multistarter fermentations
      with S. cerevisiae starter cultures.

PMID- 24443785
TI  - Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.
AB  - BACKGROUND AND AIM: Pre-transplant sarcopenia (reduced skeletal muscle mass)
      predicts poor outcome in cirrhosis. In contrast, whether muscle mass increases
      post-orthotopic liver transplantation (OLT) is not known and was studied
      prospectively. METHODS: Consecutive patients who underwent a comprehensive
      nutritional evaluation in a liver transplant nutrition clinic were included. Core
      abdominal muscle area was measured on abdominal computed tomography obtained pre-
      and post-OLT. Age- and gender-based controls were used to define sarcopenia.
      Measures of body composition pre-transplant were correlated with computed
      tomography measurements. Predictors and clinical impact of post-OLT change in
      muscle area were examined. In three subjects post-OLT and three controls,
      expression of genes regulating skeletal muscle mass were quantified. RESULTS:
      During the study period, 53 patients (M:F 41:12; age 56.9 +/- 7.5 years) were
      followed up after OLT for 19.3 +/- 9 months. Five patients died and another five
      had acute graft rejection. Pre-OLT sarcopenia was present in 33 (66.2%). Pre
      transplant clinical characteristics including Child's score, MELD score, and
      nutritional status or post-transplantation immunosuppression regimen did not
      predict post-transplant change in muscle mass. New onset post-OLT sarcopenia
      developed in 14 patients. Loss of muscle mass post-OLT increased risk of diabetes
      mellitus and a trend toward higher mortality. Skeletal muscle expression of
      myostatin was higher and that of ubiquitin proteasome proteolytic components
      lower post-OLT than in controls. CONCLUSIONS: Post-transplantation sarcopenia is
      common and could not be attributed to pre-transplant characteristics or the type
      or duration of post-OLT immunosuppression. Post-transplant sarcopenia contributes
      to adverse consequences and strategies targeting myostatin may be beneficial.

PMID- 24443787
TI  - Th17 and Treg cells in adolescents with Graves' disease. Impact of treatment with
      methimazole on these cell subsets.
AB  - The role of T helper 17 (Th17) and T regulatory cells (Treg) in the pathogenesis
      of Graves' disease (GD) remains uncertain. The influence of methimazole (MMI) on
      the human immune system is still poorly understood. The aim of the present
      research was to assess changes in the frequencies of peripheral blood Th17 and
      Treg cells during GD treatment in the group of teenagers. The frequencies of Th17
      and Treg were measured by flow cytometry in 60 adolescents at the time of GD
      diagnosis and after achieving MMI-induced euthyreosis. The control group
      consisted of 20 healthy volunteers. Lower percentages and absolute counts of Treg
      cells were found in the study group before the treatment in comparison with
      healthy controls (p = 0.032 and p = 0.006, respectively). Treatment with MMI
      caused an increase in the percentages and absolute counts of Treg lymphocytes (p
      = 0.037 and p = 0.007). After the treatment, no clinically significant
      differences in Treg cells between GD patients and controls were found. Higher
      absolute counts of Th17 lymphocytes were found in hyperthyroid adolescents before
      the treatment initiation and after achieving euthyreosis than in healthy
      individuals (p = 0.0001 and p = 0.047). Treatment with MMI caused a significant
      decrease in the percentages and absolute counts of Th17 lymphocytes (p = 0.047
      and p = 0.043). The present study demonstrates that both Th17 and Treg cells
      might play a role in the pathogenesis of GD. Increased percentage of Treg after
      MMI therapy seems a predictor of response to anti-hypertensive treatment as it is
      associated with the normalization of thyroid hormone levels.

PMID- 24443786
TI  - Epigenetic changes during hematopoietic cell granulocytic differentiation-
      comparative analysis of primary CD34+ cells, KG1 myeloid cells and mature
      neutrophils.
AB  - BACKGROUND: Epigenetic regulation is known to affect gene expression, and recent
      research shows that aberrant DNA methylation patterning and histone modifications
      may play a role in leukemogenesis. In order to highlight the co-operation of
      epigenetic mechanisms acting during the latter process it is important to clarify
      their potential as biomarkers of granulocytic differentiation. RESULTS: In this
      study we investigated epigenetic alterations in human hematopoietic cells at a
      distinct differentiation stages: primary hematopoietic CD34+ cells, KG1 myeloid
      leukemic cells, whose development is stopped at early stage of differentiation,
      and mature neutrophils. We focused on the epigenetic status of cell cycle
      regulating (p15, p16) and differentiation related (E-cadherin and RARbeta) genes.
      We found that the methylation level in promoter regions of some of these genes
      was considerably higher in KG1 cells and lower in CD34+ cells and human
      neutrophils. As examined and evaluated by computer-assisted methods, histone H3
      and H4 modifications, i.e. H3K4Me3, H3K9Ac, H3K9Ac/S10Ph and H4 hyperAc, were
      similar in CD34+ cells and human mature neutrophils. By contrast, in the KG1
      cells, histone H3 and H4 modifications were quite high and increased after
      induction of granulocytic differentiation with the HDAC inhibitor phenyl
      butyrate. CONCLUSIONS: We found the methylation status of the examined gene
      promoters and histone modifications to be characteristically associated with the
      hematopoietic cell progenitor state, induced to differentiate myeloid KG1 cells
      and normal blood neutrophils. This could be achieved through epigenetic
      regulation of E-cadherin, p15, p16 and RARbeta genes expression caused by DNA
      methylation/demethylation, core and linker histones distribution in stem
      hematopoietic cells, induced to differentiation KG1 cells and mature human
      neutrophils, as well as the histone modifications H3K4Me3, H3K9Ac, H3K9Ac/S10Ph
      and H4 hyperAc in relation to hematopoietic cell differentiation to granulocyte.
      These findings also suggest them as potentially important biomarkers of
      hematopoietic cell granulocytic differentiation and could be valuable for
      leukemia induced differentiation therapy.

PMID- 24443788
TI  - High prevalence of Y-box protein-1/p18 fragment in plasma of patients with
      malignancies of different origin.
AB  - BACKGROUND: Expression of the cold shock protein Y-box protein 1 (YB-1) is
      associated with deleterious outcome in various malignant diseases. Our group
      recently showed that the detection of an 18 kDa YB-1 fragment (YB-1/p18) in human
      plasma identifies patients with malignant diseases. We now tested the prevalence,
      clinical, and diagnostic value of YB-1/p18 detection in common tumors. METHODS: A
      newly established monoclonal YB-1 antibody was used to detect YB-1/p18 by
      immunoblotting in plasma samples from 151 unselected tumor patients, alongside
      established tumor markers and various diagnostic measures, during evaluation for
      a cancerous disease and in follow-up studies after therapeutic interventions.
      RESULTS: Circulating YB-1/p18 was detected in 78% of patients having a tumor
      disease. YB-1/p18 positivity was highly prevalent in all examined malignancies,
      including lung cancer (32/37; 87%), breast cancer (7/10; 70%), cancer of unknown
      primary (CUP; 5/5, 100%) or hematological malignancies (42/62; 68%). Positivity
      for YB-1/p18 was independent of other routine laboratory parameters, tumor stage,
      or histology. In comparison to 13 established tumor markers (cancer antigens 15
      3, 19-9, 72-4, and 125; carcinoembryonic antigen; cytokeratin fragments 21-1;
      neuron-specific enolase; alpha-fetoprotein; beta-2-microglobulin; squamous cell
      carcinoma antigen; thymidine kinase; tissue polypeptide antigen; pro-gastrin
      releasing peptide), YB-1/p18 detection within serum samples was the most
      sensitive general parameter identifying malignant disorders. YB-1/p18
      concentrations altered during therapeutic interventions, but did not predict
      prognosis. CONCLUSIONS: Plasma YB-1/p18 detection has a high specific prevalence
      in malignancies, thereby providing a novel tool for cancer screening independent
      of the tumor origin.

PMID- 24443789
TI  - Type 1 diabetes patients' experiences of, and need for, social support after
      attending a structured education programme: a qualitative longitudinal
      investigation.
AB  - AIMS AND OBJECTIVES: To explore patients' experiences of, views about and need
      for, social support after attending a structured education programme for type 1
      diabetes. BACKGROUND: Patients who attend structured education programmes attain
      short-term improvements in biomedical and quality-of-life measures but require
      support to sustain self-management principles over the longer term. Social
      support can influence patients' self-management practices; however, little is
      known about how programme graduates use other people's help. DESIGN: This study
      was informed by the principles of grounded theory and involved concurrent data
      collection and analysis. Data were analysed using an inductive, thematic
      approach. METHODS: In-depth interviews were undertaken postcourse, six and 12
      months later, with 30 adult patients with type 1 diabetes recruited from Dose
      Adjustment for Normal Eating courses in the United Kingdom. RESULTS: Patients'
      preferences for social support from other people ranged from wanting minimal
      involvement, to benefiting from auxiliary forms of assistance, to regular
      monitoring and policing. New self-management skills learnt on their courses
      prompted and facilitated patients to seek and obtain more social support. Support
      received/expected from parents varied according to when patients were diagnosed,
      but parents' use of outdated knowledge could act as a barrier to effective
      support. Support sought from others, including friends/colleagues, was informed
      by patients' domestic/employment circumstances. CONCLUSION: This study responds
      to calls for deeper understanding of the social context in which chronic illness
      self-management occurs. It highlights how patients can solicit and receive more
      social support from family members and friends after implementing self-care
      practices taught on education programmes. RELEVANCE TO CLINICAL PRACTICE: Health
      professionals including diabetes specialist nurses and dietitians should explore:
      patients' access to and preferences for social support; how patients might be
      encouraged to capitalise on social support postcourse; and new ways to
      inform/educate people within patients' social networks.

PMID- 24443790
TI  - A relational approach to health practices: towards transcending the agency
      structure divide.
AB  - Many health scholars find that Pierre Bourdieu's theory of practice leaves too
      little room for individual agency. We contend that, by virtue of its relational,
      field-theoretic underpinnings, the idea of leaving room for agency in Bourdieu's
      theory of practice is misguided. With agency manifested in interactions and
      social structures consisting of relations built upon relations, the stark
      distinction between agency and structure inherent to substantialist thinking is
      undermined, even dissolved, in a relational field-theoretic context. We also
      contend that, when treated as relationally bound phenomena, Bourdieu's notions of
      habitus, doxa, capital and field illuminate creative, adaptive and future-looking
      practices. We conclude by discussing difficulties inherent to implementing a
      relational theory of practice in health promotion and public health. 

PMID- 24443791
TI  - Impact of long-acting octreotide in patients with early-stage MEN1-related
      duodeno-pancreatic neuroendocrine tumours.
AB  - BACKGROUND: Somatostatin analogues (SSA) represent one of the main therapeutic
      option in patients affected with functioning well-differentiated neuroendocrine
      tumours (NETs). There are no studies specifically focusing on NETs associated
      with Multiple Endocrine Neoplasia type 1 (MEN1). AIM: To evaluate the efficacy of
      the long-acting SSA octreotide in MEN1 patients with early-stage duodeno
      pancreatic NETs. PATIENTS AND METHODS: Forty patients with MEN1 were
      retrospectively evaluated. Twenty patients with evidence of one or more MEN1
      related duodeno-pancreatic NETs < 20 mm in size (age range 26-61 years) were
      treated with octreotide long-acting octreotide (LAR) as first-line therapy.
      Treatment duration ranged 12-75 months. At the baseline radiological evaluation,
      multiple duodeno-pancreatic NETs (range 1-8, size 3-18 mm) were detected.
      RESULTS: An objective tumour response was observed in 10%, stable disease in 80%
      and progression of disease in 10% of cases. In six patients with abnormally
      increased CgA, gastrin and/or insulin serum concentrations, a significant
      clinical and hormonal response occurred in 100% of cases and was stable along the
      time. CONCLUSIONS: Therapy with SSA is highly safe and effective in patients with
      early-stage MEN1 duodeno-pancreatic NETs, resulting in long-time suppression of
      tumour and hormonal activity and 10% objective response. This suggests to early
      start therapy with SSA in patients with MEN1-related NETs.

PMID- 24443792
TI  - Atypical esthesioneuroblastoma invading oral cavity: a case report and review of
      the literature.
AB  - Esthesioneuroblastoma is an uncommon tumour of neuroectodermal origin. The
      authors describe a rare presentation of an atypical esthesioneuroblastoma
      invading oral cavity. The clinical presentation, aetiology, diagnosis, and
      management of this condition are discussed. The patient developed significant
      swelling in the right anterosuperior alveolar mucosa and had moderate tooth
      mobility. Conventional x-rays and computed tomography revealed a large osteolytic
      lesion, with imprecise limits. Histological findings along with
      immunohistochemical staining results and clinical features led to the diagnosis
      of high-grade esthesioneuroblastoma. Local recurrences and neck metastasis were
      detected. The rare oral findings produced delayed in diagnosis which may lead to
      a compromise in planning and execution of further radical management and thus a
      poor prognosis. VIRTUAL SLIDES: The virtual slides for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/1168853011139286.

PMID- 24443794
TI  - Understanding IFNlambda in rheumatoid arthritis.
AB  - Unraveling the mechanisms underlying the inflammatory response in rheumatoid
      arthritis is crucial in order to better understand the disease and to develop
      novel therapeutic approaches. Although the effect of type I interferons on
      fibroblasts and in the context of rheumatoid arthritis has been described for
      some time, little is known on the effects of the type III interferons, also known
      as IFNlambda. In a previous issue, Xu and colleagues demonstrate that one of the
      members of the IFNlambda family, IFNlambda1, enhances Toll-like receptor
      expression and consequently promotes the production of proinflammatory cytokines
      known to be involved in initiating and maintaining the inflammatory responses in
      rheumatoid arthritis. 

PMID- 24443793
TI  - Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard
      diabetes therapy on cardiovascular and microvascular outcomes.
AB  - AIMS: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, has
      been shown to lower glycated hemoglobin (HbA1c), weight, blood pressure and serum
      uric acid in clinical trials. Plasma lipids were also evaluated as exploratory
      variables. The goal of this study was to estimate the long-term cardiovascular
      (CV) and microvascular outcomes of dapagliflozin added to the standard of care
      (SOC) versus SOC using simulation methodology. METHODS: The Archimedes Model, a
      validated model of human physiology, diseases and healthcare systems, was used to
      model a type 2 diabetes mellitus (T2DM) population derived from National Health
      and Nutrition Examination Survey (NHANES) with HbA1c 7-10%, taking a single oral
      antidiabetic agent [metformin, sulfonylureas SU or thiazolidinedione (TZD)] at
      the beginning of the trial. A 20-year trial was simulated comparing dapagliflozin
      10 mg, given in addition to SOC, with SOC alone. SOC was based on American
      Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD)
      2012 guidelines and included diet, metformin, SU, TZD, dipeptidyl peptidase-4
      (DPP-4), glucagon-like peptide-1 (GLP-1), and insulin therapies, with usage
      levels reflective of those in NHANES. Dapagliflozin effects were derived from
      phase 3 clinical trial results. End points included CV and microvascular
      outcomes. RESULTS: Over a 20-year period, patients on dapagliflozin were
      projected to experience relative reductions in the incidence of myocardial
      infarction (MI), stroke, CV death, and all-cause death of 13.8, 9.1, 9.6 and
      5.0%, respectively, and relative reductions in the incidence of end-stage renal
      disease (ESRD), foot amputation, and diabetic retinopathy of 18.7, 13.0 and 9.8%,
      respectively, when compared with SOC. CONCLUSIONS: On the basis of simulation
      results, adding dapagliflozin to currently available treatment options is
      projected to further decrease the CV and microvascular complications associated
      with T2DM.

PMID- 24443795
TI  - Electrical stimulation for difficult wounds: only an alternative procedure?
AB  - In the wound healing research, the exact mechanism of action of different
      modalities of electrical stimulation (ES) remains controversial and unresolved.
      In this study we discuss a particular ES, with a different type of waveform,
      corresponding to the principle of stochastic resonance. Between July 2008 and May
      2010, 32 patients were enrolled and ES was applied to wounds using the
      bioelectrical signal therapy (BST) device (LifeWave, Petach Tiqwa, Israel). The
      outcome evaluated in group 1 (n = 21) was wound healing, while group 2 (n = 11)
      was evaluated for wound-related pain [Visual Number Scale (VNS) pain scale]
      during treatment. In group 1, 87% of the wounds closed in an average time of 97
      days (range 10-150 days); three patients were lost to follow-up. In group 2, 45%
      of the patients experienced a complete pain disappearance after 7 days of
      treatment; 36% reported a reduction in VNS from 9.3 to 3.2 in 7 days; 19% stopped
      morphine-like painkillers after 2 weeks. The clinical application of the
      stochastic resonance enables the usage of easy-to-use, non-invasive, painless and
      pain-relief treatment. Our experience with ES has demonstrated the BST device to
      be a very good alternative in cases of small size defects, compared with other
      therapies such as surgery, dressing and negative pressure devices. 

PMID- 24443796
TI  - An exploration of how nurse prescribing is being used for patients with
      respiratory conditions across the east of England.
AB  - BACKGROUND: There is a need to reduce symptoms, exacerbations and improve quality
      of life for patients with respiratory diseases. Across the world, increasing
      numbers of nurses are adopting the prescribing role and can potentially enhance
      service provision. Evidence suggests improved quality of care and efficiencies
      occur when nurses adopt the prescribing role. No evidence is available on the
      views of nurse prescribers who care for respiratory patients. The aim was to
      explore how nurse prescribing is being used for patients with respiratory
      conditions in different care settings across one strategic health authority, and
      whether this has benefited patients, healthcare professionals and the National
      Health Service. METHODS: A qualitative study involving semi-structured interviews
      with a purposive sample of 40 nurses who prescribed for respiratory patients
      across the six counties in the East of England Strategic Health Authority. Data
      were collected in 2011 and subject to thematic analysis. RESULTS: Disease
      management, including treatment and prevention of exacerbations, emergency
      episodes and minor illness, optimising and co-ordinating care were key aspects of
      care provided. Findings are reported under three themes: access, adherence and
      risk management and impact on nurses. Prescribing enabled nurses overcome
      existing problems in service provision to improve access, efficiency and patient
      convenience, reducing hospital admissions and length of stay. It also enabled
      patient centered consultations, which encouraged self-management, improved
      adherence, helped manage expectations, and reduced inappropriate service use.
      While participants experienced increased job satisfaction, knowledge and
      confidence, concerns were raised about increased responsibility, support,
      governance and future commissioning of services in line with planned major
      changes to the National Health Service. CONCLUSIONS: This study provides new
      knowledge about how nurse prescribers provide care to patients with respiratory
      diseases. Despite a lack of consensus over the most effective model of
      respiratory care, prescribing was reported to have improved and extended points
      of access to treatment, and supported management of complex patients,
      particularly vulnerable groups. Given the high burden of chronic respiratory
      disease to patients and families this has important implications that need to be
      considered by those responsible for commissioning services in the United Kingdom
      and other countries.

PMID- 24443797
TI  - DSM-5 disruptive mood dysregulation disorder: correlates and predictors in young
      children.
AB  - BACKGROUND: Despite the inclusion of disruptive mood dysregulation disorder
      (DMDD) in DSM-5, little empirical data exist on the disorder. We estimated rates,
      co-morbidity, correlates and early childhood predictors of DMDD in a community
      sample of 6-year-olds. METHOD: DMDD was assessed in 6-year-old children (n = 462)
      using a parent-reported structured clinical interview. Age 6 years correlates and
      age 3 years predictors were drawn from six domains: demographics; child
      psychopathology, functioning, and temperament; parental psychopathology; and the
      psychosocial environment. RESULTS: The 3-month prevalence rate for DMDD was 8.2%
      (n = 38). DMDD occurred with an emotional or behavioral disorder in 60.5% of
      these children. At age 6 years, concurrent bivariate analyses revealed
      associations between DMDD and depression, oppositional defiant disorder, the
      Child Behavior Checklist - Dysregulation Profile, functional impairment, poorer
      peer functioning, child temperament (higher surgency and negative emotional
      intensity and lower effortful control), and lower parental support and marital
      satisfaction. The age 3 years predictors of DMDD at age 6 years included child
      attention deficit hyperactivity disorder, oppositional defiant disorder, the
      Child Behavior Checklist - Dysregulation Profile, poorer peer functioning, child
      temperament (higher child surgency and negative emotional intensity and lower
      effortful control), parental lifetime substance use disorder and higher parental
      hostility. CONCLUSIONS: A number of children met DSM-5 criteria for DMDD, and the
      diagnosis was associated with numerous concurrent and predictive indicators of
      emotional and behavioral dysregulation and poor functioning.

PMID- 24443798
TI  - Retrospective analysis of mortalities in a tertiary care hospital in Northeast
      Ethiopia.
AB  - BACKGROUND: Mortalities in the health care set up are prevalent, and causes are
      multifactorial with variations from area to area and also from ward to ward in
      the same health care set up. Analysis of mortalities and its causes in Ethiopian
      hospitals including Dessie Referral Hospital is not adequately known. Thus, the
      aim of this study is to determine the prevalence of mortalities and its causes in
      the Dessie Referral Hospital, Northeast Ethiopia. METHODS: A retrospective
      analysis of mortalities during a three year period (September 2010-2012) was
      conducted in the Dessie Referral Hospital from August-September, 2012. All in
      hospital mortalities in the hospital during the last three years were included in
      the study. Data were collected from patient discharge recording books. Finally,
      data were entered into SPSS windows version 16.0 and descriptive statistics were
      generated to meet the study objective. RESULTS: During the last 3 years there
      were 1,481 (4.8%) mortalities in the hospital. Around 60.0% of the mortalities
      were among male patients, and two third of the mortalities were among patients
      aged 15 years or older. The majority of the mortalities (38.9%) were in the
      medical ward followed by pediatric (34.6%) and surgical (18.2%) wards. Most of
      the mortalities (34.8%) occurred during 2011 while least was in 2012 (31.8%).
      HIV/AIDS (14.8%), pneumonia (9.9%), and sepsis/shock (7.6%) were the three most
      common causes of mortality in the hospital during the three year period. On
      average, patients stayed for 2.86 (+/-2. 99) days in the wards before mortality.
      CONCLUSION: Mortalities in the wards of the Dessie Referral Hospital were high
      and the causes were mainly of infectious origin, HIV/AIDS and its complications
      being the most common causes. This calls for an integrated effort to reduce in
      hospital mortalities by equipping the hospital and its health care providers with
      the skills and medical supplies required for proper management of the most common
      causes of in hospital mortality reported in this study.

PMID- 24443799
TI  - MiR-133b is frequently decreased in gastric cancer and its overexpression reduces
      the metastatic potential of gastric cancer cells.
AB  - BACKGROUND: Emerging evidence has shown that microRNAs are involved in gastric
      cancer development and progression. Here we examine the role of miR-133b in
      gastric cancer. METHODS: Quantitative real-time PCR analysis was performed in 140
      patient gastric cancer tissues and 8 gastric cancer cell lines. The effects of
      miR-133b in gastric cancer cells metastasis were examined by scratch assay,
      transwell migration and matrigel invasion. In vivo effects of miR-133b were
      examined in an intraperitoneal mouse tumor model. Targets of miR-133b were
      predicted by bioinformatics tools and validated by luciferase reporter analyses,
      western blot, and quantitative real-time PCR. RESULTS: MiR-133b was significantly
      downregulated in 70% (98/140) of gastric cancer patients. Expression of miR-133b
      was negatively correlated with lymph node metastasis of gastric cancer in
      patients. Similarly, the expression of miR-133b was significantly lower in seven
      tested gastric cancer cell lines than in the immortalized non-cancerous GES-1
      gastric epithelial cells. Overexpression of miR-133b markedly inhibited
      metastasis of gastric cancer cells in vitro and in vivo. Moreover, the
      transcriptional factor Gli1 was identified as a direct target for miR-133b. Level
      of Gli1 protein but not mRNA was decreased by miR-133b. Activity of luciferase
      with Gli1 3'-untranslated region was markedly decreased by miR-133b in gastric
      cancer cells. Gli1 target genes, OPN and Zeb2, were also inhibited by miR133b.
      CONCLUSIONS: MiR-133b is frequently decreased in gastric cancer. Overexpression
      of miR-133b inhibits cell metastasis in vitro and in vivo partly by directly
      suppressing expression of Gli1 protein. These results suggested that miR-133b
      plays an important role in gastric cancer metastasis.

PMID- 24443800
TI  - A comprehensive microRNA expression profile of the backfat tissue from castrated
      and intact full-sib pair male pigs.
AB  - BACKGROUND: It is widely known that castration has a significant effect on the
      accumulation of adipose tissue. microRNAs (miRNAs) are known to be involved in
      fat deposition and to be regulated by the androgen-induced androgen receptor
      (AR). However, there is little understanding of the relationship between miRNAs
      and fat deposition after castration. In this study, the high-throughput SOLiD
      sequencing approach was used to identify and characterize miRNA expression in
      backfat from intact and castrated full-sib male 23-week-old pigs. The patterns of
      adipogenesis and fat deposition were compared between castrated and intact male
      pigs. RESULTS: A total of 366 unique miRNA genes were identified, comprising 174
      known pre-miRNAs and 192 novel pre-miRNAs. One hundred and sixty-seven pre-miRNAs
      were common to both castrated (F3) and intact (F4) male pig small RNA libraries.
      The novel pre-miRNAs encoded 153 miRNAs/miRNA*s and 141 miRNAs/miRNA*s in the F3
      and F4 libraries, respectively. One hundred and seventy-seven miRNAs, including
      45 up- and 132 down-regulated, had more than 2-fold differential expression
      between the castrated and intact male pigs (p-value < 0.001). Thirty-five miRNAs
      were further selected, based on the expression abundance and differentiation
      between the two libraries, to predict their targets in KEGG pathways. KEGG
      pathway analyses suggested that miRNAs differentially expressed between the
      castrated and intact male pigs are involved in proliferation, apoptosis,
      differentiation, migration, adipose tissue development and other important
      biological processes. The expression patterns of eight arbitrarily selected
      miRNAs were validated by stem-loop reverse-transcription quantitative polymerase
      chain reaction. These data confirmed the expression tendency observed with SOLiD
      sequencing. miRNA isomiRs and mirtrons were also investigated in this study.
      Mirtrons are a recently described category of miRNA relying on splicing rather
      than processing by the microprocessor complex to generate the RNAi pathway. The
      functions of miRNAs important for regulating fat deposition were also
      investigated in this study. CONCLUSIONS: This study expands the number of fat
      deposition-related miRNAs in pig. The results also indicate that castration can
      significantly affect the expression patterns of fat-related miRNAs. The
      differentially expressed miRNAs may play important roles in fat deposition after
      castration.

PMID- 24443801
TI  - Case report: Intraductal tubulopapillary neoplasm of the pancreas with unique
      clear cell phenotype.
AB  - Intraductal tubulopapillary neoplasms of the pancreas are very rare tumors
      characterized by intraductal tubulopapillary growth, ductal differentiation,
      scant intracellular mucin production and cellular dysplasia. Here, we report the
      first case of an intraductal tubulopapillary neoplasm of the pancreas with clear
      cell morphology. The tumor was detected during the diagnostic work-up of acute
      pancreatitis in a 43- year old female. Histological examination revealed a tumor
      with the typical architecture of an intraductal tubulopapillary neoplasm of the
      pancreas with tumor cells showing abundant clear cytoplasm and Di-PAS negativity.
      Immunohistochemistry revealed positivity for Pan-CK, CK7, CK8/18, MUC1, MUC6,
      carbonic anhydrase IX, CD10, EMA, beta-catenin and e-cadherin. Sanger sequencing
      did not detect mutations for beta-catenin, BRAF, KRAS, PIK3CA and GNAS.
      Altogether, histology, immunohistochemical expression profile (MUC1+, MUC6+, MUC2
      , MUC5AC-, thrypsin-, chymotrypsin-, CDX2-) and sequencing results led to the
      diagnosis of intraductal tubulopapillary neoplasm. However, the neoplasm
      consisted of cells showing abundant clear cytoplasm, a morphological pattern not
      being described so far in the current classification of pancreatic intraductal
      neoplasms. Potential differential diagnosis and the molecular basis of clear cell
      morphology are discussed. In conclusion, we consider this tumor as intraductal
      tubulopapillary neoplasm of the pancreas with unique clear cell phenotype. After
      surgery and without adjuvant therapy, the patient's clinical course has been
      uneventful for over two years now. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1051828790117127.

PMID- 24443802
TI  - Biotechnological production of carotenoids by yeasts: an overview.
AB  - Nowadays, carotenoids are valuable molecules in different industries such as
      chemical, pharmaceutical, poultry, food and cosmetics. These pigments not only
      can act as vitamin A precursors, but also they have coloring and antioxidant
      properties, which have attracted the attention of the industries and researchers.
      The carotenoid production through chemical synthesis or extraction from plants is
      limited by low yields that results in high production costs. This leads to
      research of microbial production of carotenoids, as an alternative that has shown
      better yields than other aforementioned. In addition, the microbial production of
      carotenoids could be a better option about costs, looking for alternatives like
      the use of low-cost substrates as agro-industrials wastes. Yeasts have
      demonstrated to be carotenoid producer showing an important growing capacity in
      several agro-industrial wastes producing high levels of carotenoids. Agro
      industrial wastes provide carbon and nitrogen source necessary, and others
      elements to carry out the microbial metabolism diminishing the production costs
      and avoiding pollution from these agro-industrial wastes to the environmental.
      Herein, we discuss the general and applied concepts regarding yeasts carotenoid
      production and the factors influencing carotenogenesis using agro-industrial
      wastes as low-cost substrates. 

PMID- 24443803
TI  - Clinical characteristics and sensitivity to food and inhalants among children
      with eosinophilic esophagitis.
AB  - BACKGROUND: To understand the clinical characteristics and the diagnostic
      procedures in pediatric patients with eosinophilic esophagitis and to evaluate
      the sensitivity of the patients to food and inhalant allergens. A cross-sectional
      study was performed in 35 children with eosinophilic esophagitis during the time
      period from January 2010 to January 2011. The clinical and epidemiological data
      were obtained using a questionnaire and medical chart analysis. The body mass
      index for age was used for the nutritional evaluation (via the Z score). The
      sensitivity to foods and inhalants was evaluated by performing a skin prick test
      and atopy patch test. RESULTS: Patients (35 in total, median age 10 years) with a
      diagnosis of eosinophilic esophagitis were evaluated. The most prevalent symptoms
      in the patients were vomiting (71.4%) and abdominal pain (51.4%). Endoscopic
      alterations were observed in 97.2% of the patients. A good nutritional state was
      observed in 82.8% of the children. The tests demonstrated the presence of food
      sensitivities and/or aeroallergens in 27 (77.1%) patients, whereas 8 (22.9%)
      patients did not test positive in any of the tests performed. Among the patients
      with positive tests, 24 (68.5%) exhibited sensitivity to aeroallergens and 16
      (45.7%) were sensitive to foods. The comparison between the sensitive and
      insensitive groups displayed statistically significant results with respect to
      sex, symptom prevalence, and 24-hour esophageal pH monitoring. CONCLUSIONS: The
      patients evaluated in this study displayed clinical characteristics of
      eosinophilic esophagitis similar to those reported in the literature. The
      sensitivity to foods determined by the tests was less than that observed in prior
      studies; however, a marked sensitivity to aeroallergens was observed. The
      different allergen sensitivity profiles observed in this study suggests that,
      similar to asthma, the eosinophiic esophagitis disease may exhibit several
      phenotypes.

PMID- 24443805
TI  - Newly qualified South African nurses' lived experience of the transition from
      student to community service nurse: a phenomenological study.
AB  - BACKGROUND: This study attempted to fill a gap in the published South African
      literature regarding newly qualified nurses' preparedness for and experience of
      role transition to a 1-year compulsory commitment of community service nurse.
      METHODS: Husserlian descriptive phenomenology, characterized by inductive
      extraction of units of meaning from transcribed audiotaped recordings, was used
      to establish the "essence" of the lived experience of role transition. Data were
      collected from eight participants through two semistructured individual
      interviews: in July 2011, 2 weeks before the start of community service, and in
      September 2011, 6 weeks after community service placement. RESULTS: Findings
      showed that before placement, participants experienced a sense of achievement in
      having successfully completed a 4-year diploma program. However, they also
      experienced uncertainty and fear about the immediate future. In the first month
      after placement, community service nurses experienced reality shock. CONCLUSION:
      Preparation for the role transition from student nurse to graduate community
      service nurse requires a 4-year structured program that includes training in
      conflict management, assertiveness, and practical ethics.

PMID- 24443804
TI  - Intra-articular hyaluronic acid injection versus oral non-steroidal anti
      inflammatory drug for the treatment of knee osteoarthritis: a multi-center,
      randomized, open-label, non-inferiority trial.
AB  - INTRODUCTION: While many of the commonly used conservative treatments for knee
      osteoarthritis (OA) have been recognized to be effective, there is still
      insufficient evidence available. Among the pharmacological treatments for knee
      OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are
      recommended for the management of OA. However, frequent and serious adverse
      effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic
      acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and
      improve joint function. However, there has been no qualified direct comparison
      study of the efficacy and safety between IA-HA and NSAIDs for patients with knee
      OA. The aim of this study was to clarify the efficacy and safety of early-phase
      IA-HA in comparison to those of NSAIDs for patients with knee OA. METHODS: This
      multicenter, randomized, open-label, parallel-group, non-inferiority comparison
      study with an oral NSAID involved a total of 200 patients with knee OA. An
      independent, computer-generated randomization sequence was used to randomly
      assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n =
      100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the
      percentage change in the patient-oriented outcome measure for knee OA, the
      Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned
      regarding any adverse events during treatment. The full analysis set (FAS) was
      used for analysis. The margin of non-inferiority was 10%. RESULTS: The analyses
      of primary endpoint included 98 patients in the IA-HA group and 86 patients in
      the NSAID group. The difference in the percentage changes of the JKOM score
      between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2%
      (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA
      HA was not inferior to NSAID. The frequency of both withdrawal and adverse events
      in the IA-HA group were significantly lower than those in the NSAID group (P =
      0.026 and 0.004, respectively). CONCLUSIONS: The early efficacy of IA-HA is
      suggested to be not inferior to that of NSAIDs, and that the safety of the early
      phase of IA-HA is superior to that of NSAIDs for patients with knee OA. TRIAL
      REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000001026.

PMID- 24443806
TI  - Creating an innovative educational structure to support best practice among
      novice nurses.
AB  - In today's complex health care environment, staff nurses are responsible for
      having the skills to analyze complicated patient situations, develop complex
      plans of care, and skillfully communicate with the health care team. The
      establishment of a new progressive care unit presented a unique opportunity to
      create innovative educational structures. Expert nurses developed successful
      strategies that can be incorporated on any unit to facilitate learning for all
      nurses. The "Teach Me Tuesday" structure was created to enhance patient safety
      and information sharing. A more formal class, Cardiac Construction 101, was
      developed to help novice nurses fill their figurative tool box with skills to
      care for complex patients. Distinct courses of treatment for patients on the unit
      were selected for "Third Thursday" case studies.

PMID- 24443807
TI  - The effect of the environment on symptom dimensions in the first episode of
      psychosis: a multilevel study.
AB  - BACKGROUND: The extent to which different symptom dimensions vary according to
      epidemiological factors associated with categorical definitions of first-episode
      psychosis (FEP) is unknown. We hypothesized that positive psychotic symptoms,
      including paranoid delusions and depressive symptoms, would be more prominent in
      more urban environments. METHOD: We collected clinical and epidemiological data
      on 469 people with FEP (ICD-10 F10-F33) in two centres of the Aetiology and
      Ethnicity in Schizophrenia and Other Psychoses (AESOP) study: Southeast London
      and Nottinghamshire. We used multilevel regression models to examine
      neighbourhood-level and between-centre differences in five symptom dimensions
      (reality distortion, negative symptoms, manic symptoms, depressive symptoms and
      disorganization) underpinning Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN) Item Group Checklist (IGC) symptoms. Delusions of
      persecution and reference, along with other individual IGC symptoms, were
      inspected for area-level variation. RESULTS: Reality distortion [estimated effect
      size (EES) 0.15, 95% confidence interval (CI) 0.06-0.24] and depressive symptoms
      (EES 0.21, 95% CI 0.07-0.34) were elevated in people with FEP living in more
      urban Southeast London but disorganized symptomatology was lower (EES -0.06, 95%
      CI -0.10 to -0.02), after controlling for confounders. Delusions of persecution
      were not associated with increased neighbourhood population density [adjusted
      odds ratio (aOR) 1.01, 95% CI 0.83-1.23], although an effect was observed for
      delusions of reference (aOR 1.41, 95% CI 1.12-1.77). Hallucinatory symptoms
      showed consistent elevation in more densely populated neighbourhoods (aOR 1.32,
      95% CI 1.09-1.61). CONCLUSIONS: In people experiencing FEP, elevated levels of
      reality distortion and depressive symptoms were observed in more urban, densely
      populated neighbourhoods. No clear association was observed for paranoid
      delusions; hallucinations were consistently associated with increased population
      density. These results suggest that urban environments may affect the syndromal
      presentation of psychotic disorders.

PMID- 24443809
TI  - Descemet membrane endothelial keratoplasty in cases with existing scleral-sutured
      and iris-sutured intraocular lenses.
AB  - BACKGROUND: To report two cases of Descemet Membrane Endothelial Keratoplasty
      (DMEK) in patients with existing scleral-fixated and iris-fixated intraocular
      lenses (sf-IOL and if-IOL, respectively). CASE PRESENTATION: DMEK procedures were
      performed on a 49-year-old woman with a pre-existing sf-IOL (case 1) and a 69
      year-old woman with a pre-existing if-IOL (case 2) in order to treat secondary
      corneal edema due to pseudophakic bullous keratopathy. Visual acuity, refractive
      error, intraocular pressure, slit lamp examination, pachymetry measurements and
      endothelial cell density (ECD) were considered and repeated during follow
      ups.Both cases had no intraoperative complications. At postoperative day 1 graft
      centration and complete attachment were noted. The IOL positions were unchanged
      in comparison to their preoperative positions. In case 1, visual acuity improved
      from 1/15 at 1 meter preoperative to 20/200 within one week and to 20/63 within
      12 weeks of follow up. In case 2, visual acuity improved from counting fingers at
      1 meter preoperative to 20/200 within one week and to 20/100 within 12 weeks of
      follow-up. In case 2 a partial graft dislocation was observed at postoperative
      day twenty. Complete graft re-apposition was achieved by rebubbling procedure
      performed with intracameral air injection. CONCLUSIONS: DMEK surgery in the
      treatment of pseudophakic bullous keratopathy in the presence of sf-IOL and if
      IOL can successfully be performed. These eyes are at increased risk of IOL
      dislocation into the vitreous cavity during DMEK surgery.

PMID- 24443810
TI  - A new cinnamoylglycoflavonoid, antimycobacterial and antioxidant constituents
      from Heritiera littoralis leaf extracts.
AB  - A new cinnamolyglycoflavonoid 3-cinnamoyltribuloside (1), its precursor
      tribuloside and two known flavonoid glycosides afzelin and astilbin were isolated
      from Heritiera littoralis Dryand (Sterculiaceae) ethanolic leaf extract. The
      dichloromethane leaf extract afforded two known pentacyclic triterpenoids, 3beta
      taraxerol and friedelin. Extracts and compounds isolated therefrom, with the
      exception of 3beta-taraxerol, exhibited antimycobacterial activity against the
      non-pathogenic Mycobacterium species Mycobacterium madagascariense and
      Mycobacterium indicus pranii, with a minimum inhibitory concentration (MIC) 5.0
      mg/mL for the crude extracts and MICs in the range of 1.6-0.8 mg/mL for the pure
      compounds. The extracts together with 3-cinnamoyltribuloside (1), tribuloside and
      astilbin exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. The
      compounds that showed dual activities could be further evaluated under clinical
      settings for co-administration with standard anti-tuberculosis drugs. 

PMID- 24443812
TI  - Characteristics of autobiographical memories and prospective imagery across a
      spectrum of hypomanic personality traits.
AB  - Evidence of a strong causal relationship between mental imagery and emotion has
      informed psychological conceptualisations of disordered positive mood states
      (i.e., mania). Holmes et al.'s cognitive model of bipolar disorder asserts a
      prominent role for intrusive and affect-laden positive imagery of the past and
      the future in the amplification and maintenance of positive mood and associated
      manic behaviours. The aims of the current study were two-fold: (1) to test
      aspects of this model in a non-clinical population sampled for hypomanic
      personality traits and (2) to examine the phenomenological characteristics of
      positive autobiographical memories and imagery of the future. Undergraduate
      students (N = 80) completed a battery of self-report questionnaires and rated
      their positive and negative memories and images of the future on a number of
      dimensions. We found significant positive correlations between hypomanic
      tendencies and the (1) everyday experience and use of mental imagery, (2)
      experience of intrusive mental imagery of future events, (3) emotional intensity
      and sensory detail of positive but not negative autobiographical memories.
      Results are discussed in the context of their theoretical and clinical
      implications, and directions for future research are considered.

PMID- 24443808
TI  - Identification of mechanosensitive genes during skeletal development: alteration
      of genes associated with cytoskeletal rearrangement and cell signalling pathways.
AB  - BACKGROUND: Mechanical stimulation is necessary for regulating correct formation
      of the skeleton. Here we test the hypothesis that mechanical stimulation of the
      embryonic skeletal system impacts expression levels of genes implicated in
      developmentally important signalling pathways in a genome wide approach. We use a
      mutant mouse model with altered mechanical stimulation due to the absence of limb
      skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects
      in skeletal elements including delayed ossification, changes in the size and
      shape of cartilage rudiments and joint fusion. We used Microarray and RNA
      sequencing analysis tools to identify differentially expressed genes between
      muscle-less and control embryonic (TS23) humerus tissue. RESULTS: We found that
      680 independent genes were down-regulated and 452 genes up-regulated in humeri
      from muscle-less Spd embryos compared to littermate controls (at least 2-fold;
      corrected p-value <=0.05). We analysed the resulting differentially expressed
      gene sets using Gene Ontology annotations to identify significant enrichment of
      genes associated with particular biological processes, showing that removal of
      mechanical stimuli from muscle contractions affected genes associated with
      development and differentiation, cytoskeletal architecture and cell signalling.
      Among cell signalling pathways, the most strongly disturbed was Wnt signalling,
      with 34 genes including 19 pathway target genes affected. Spatial gene expression
      analysis showed that both a Wnt ligand encoding gene (Wnt4) and a pathway
      antagonist (Sfrp2) are up-regulated specifically in the developing joint line,
      while the expression of a Wnt target gene, Cd44, is no longer detectable in
      muscle-less embryos. The identification of 84 genes associated with the
      cytoskeleton that are down-regulated in the absence of muscle indicates a number
      of candidate genes that are both mechanoresponsive and potentially involved in
      mechanotransduction, converting a mechanical stimulus into a transcriptional
      response. CONCLUSIONS: This work identifies key developmental regulatory genes
      impacted by altered mechanical stimulation, sheds light on the molecular
      mechanisms that interpret mechanical stimulation during skeletal development and
      provides valuable resources for further investigation of the mechanistic basis of
      mechanoregulation. In particular it highlights the Wnt signalling pathway as a
      potential point of integration of mechanical and molecular signalling and
      cytoskeletal components as mediators of the response.

PMID- 24443813
TI  - Diffuse panbronchiolitis in a patient with common variable immunodeficiency: a
      casual association or a pathogenetic correlation?
AB  - Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease that seems
      to have an immunological pathogenesis and that causes a severe progressive
      suppurative and obstructive respiratory disorder. Common variable
      immunodeficiency (CVID) is the most common serious primary immunodeficiency and
      it is often associated with respiratory diseases. Herein, we describe a case of
      DPB in a 41-year-old man affected by CVID. We examined the patient's lungs,
      focusing on the characteristics of the inflammatory cells and of the foamy
      macrophagic nodules typical of DPB. Immunohistochemical typing of the lymphocytic
      infiltrate showed that B-cells were almost absent, matching the immunological
      profile of CVID. The case described is the first case reported in the literature
      of DPB in a patient affected by CVID. Moreover it seems to confirm the
      correlation between an immunodeficiency status and the development of DPB and
      provides more information on the accumulation of nodules of foamy macrophages in
      DPB. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5310709471138338.

PMID- 24443814
TI  - Broadening the lens: university students and breastfeeding attitudes.

PMID- 24443816
TI  - Electrodeposition of triangular Pd rod nanostructures and their electrocatalytic
      and SERS activities.
AB  - We report a simple one-step electrodeposition of triangular Pd rod nanostructures
      on clean Au substrates without additives. Scanning electron microscopy,
      transmission electron microscopy, and electrochemical techniques were utilized to
      characterize the structural features of the triangular Pd rod nanostructures. The
      regulation of the electrodeposition rate by optimizing the electrolyte
      concentration and applied potential was critical for the anisotropic growth of Pd
      in the vertical direction. The triangular Pd rod structures exhibited
      electrocatalytic activities for oxygen reduction and methanol oxidation
      reactions. These surfaces could be effectively utilized as reproducible surface
      enhanced Raman scattering (SERS) active substrates to produce stable SERS signals
      under electrochemical systems. A simple preparation of well-defined triangular Pd
      rod structures would allow new opportunities in various areas utilizing Pd-based
      nanostructured surfaces. 

PMID- 24443815
TI  - Birth weight, childhood body mass index, and height in relation to mammographic
      density and breast cancer: a register-based cohort study.
AB  - INTRODUCTION: High breast density, a strong predictor of breast cancer may be
      determined early in life. Childhood anthropometric factors have been related to
      breast cancer and breast density, but rarely simultaneously. We examined whether
      mammographic density (MD) mediates an association of birth weight, childhood body
      mass index (BMI), and height with the risk of breast cancer. METHODS: 13,572
      women (50 to 69 years) in the Copenhagen mammography screening program (1991
      through 2001) with childhood anthropometric measurements in the Copenhagen School
      Health Records Register were followed for breast cancer until 2010. With logistic
      and Cox regression models, we investigated associations among birth weight,
      height, and BMI at ages 7 to 13 years with MD (mixed/dense or fatty) and breast
      cancer, respectively. RESULTS: 8,194 (60.4%) women had mixed/dense breasts, and
      716 (5.3%) developed breast cancer. Childhood BMI was significantly inversely
      related to having mixed/dense breasts at all ages, with odds ratios (95%
      confidence intervals) ranging from 0.69 (0.66 to 0.72) at age 7 to 0.56 (0.53 to
      0.58) at age 13, per one-unit increase in z-score. No statistically significant
      associations were detected between birth weight and MD, height and MD, or birth
      weight and breast cancer risk. BMI was inversely associated with breast cancer,
      with hazard ratios of 0.91 (0.83 to 0.99) at age 7 and 0.92 (0.84 to 1.00) at age
      13, whereas height was positively associated with breast cancer risk (age 7, 1.06
      (0.98 to 1.14) and age 13, 1.08 (1.00 to 1.16)). After additional adjustment for
      MD, associations of BMI with breast cancer diminished (age 7, 0.97 (0.88 to 1.06)
      and age 13, 1.01 (0.93 to 1.11)), but remained with height (age 7, 1.06 (0.99 to
      1.15) and age 13, 1.09 (1.01 to 1.17)). CONCLUSIONS: Among women 50 years and
      older, childhood body fatness was inversely associated with the breast cancer
      risk, possibly via a mechanism mediated by MD, at least partially. Childhood
      tallness was positively associated with breast cancer risk, seemingly via a
      pathway independent of MD. Birth weight was not associated with MD or breast
      cancer in this age group.

PMID- 24443818
TI  - In situ optical and structural studies on photoluminesence quenching in
      CdSe/CdS/Au heterostructures.
AB  - We report here detailed in situ studies of nucleation and growth of Au on
      CdSe/CdS nanorods using synchrotron SAXS technique and time-resolved
      spectroscopy. We examine structural and optical properties of CdSe/CdS/Au
      heterostructures formed under UV illumination. We compare the results for
      CdSe/CdS/Au heterostructures with the results of control experiments on CdSe/CdS
      nanorods exposed to gold precursor under conditions when no such heterostructures
      are formed (no UV illumination). Our data indicate similar photoluminescence (PL)
      quenching and PL decay profiles in both types of samples. Via transient
      absorption and PL, we show that such behavior is consistent with rapid (faster
      than 3 ps) hole trapping by gold-sulfur sites at the surface of semiconductor
      nanoparticles. This dominant process was overlooked in previous end-point studies
      on semiconductor/metal heterostructures. 

PMID- 24443817
TI  - Analysis of a sample of type 2 diabetic patients with obesity or overweight and
      at cardiovascular risk: a cross sectional study in Spain.
AB  - BACKGROUND: The multifactorial control of diabetes relies on interventions that
      provide patients with the best knowledge and resources available. The objective
      of this research was to analyze the clinical characteristics of a sample of
      people with type 2 diabetes at high cardiovascular risk, and establish possible
      links between disease control, family history and lifestyle, to improve the
      quality of interventions. Family history, lifestyle habits, blood pressure,
      anthropometric data and laboratory tests were analyzed in this descriptive and
      comparative cross-sectional study. RESULTS: All patients had a pathological body
      mass index (BMI), and in those patients with a family history of diabetes, the
      disease was more serious and onset was earlier. Overall, 70.9% were taking drugs
      for arterial blood pressure management, with mean values within recommended
      limits; 87.1% were taking antihyperlipidemic drugs and had mean values for blood
      lipids within reference range; 93.5% were receiving oral antidiabetic drugs
      and/or insulin and had blood glucose and glycosylated hemoglobin (HbA1c) values
      higher than recommended limit; and 87% were taking antiplatelet drugs and had
      fibrinogen and ultrasensitive C-reactive protein higher than the normal range.
      High HbA1c values were found in a high proportion of our sample who were not
      following a tailored diet (84.2%), and better BMIs were associated with moderate
      physical activity. Coexistence of somatic disorders (97.4% of the sample with
      musculoskeletal diseases) could lead to the lack of physical activity.
      CONCLUSIONS: This sample of patients with type 2 diabetes and at high
      cardiovascular risk, had acceptable metabolic control, facilitated by drug
      therapy. Family history of diabetes was associated with earlier disease onset and
      worse disease progression. Patients who were not following a tailored diet had
      worse HbA1c values compared with those who were. Individuals who practiced
      moderate physical activity in line with international recommendations for weight
      maintenance had the best BMI values, but the high prevalence of comorbidities
      could adversely affect exercise habits. Appropriate use of medication, dietary
      advice, and tailored physiotherapy physical activity suitable for people with
      comorbidities should be included in multifactorial treatment strategies for these
      patients, particularly in the presence of a family history of diabetes.

PMID- 24443819
TI  - Thiol-ene mediated neoglycosylation of collagen patches: a preliminary study.
AB  - Despite the relevance of carbohydrates as cues in eliciting specific biological
      responses, the covalent surface modification of collagen-based matrices with
      small carbohydrate epitopes has been scarcely investigated. We report thereby the
      development of an efficient procedure for the chemoselective neoglycosylation of
      collagen matrices (patches) via a thiol-ene approach, between alkene-derived
      monosaccharides and the thiol-functionalized material surface. Synchrotron
      radiation-induced X-ray photoelectron spectroscopy (SR-XPS), Fourier transform
      infrared (FT-IR), and enzyme-linked lectin assay (ELLA) confirmed the
      effectiveness of the collagen neoglycosylation. Preliminary biological evaluation
      in osteoarthritic models is reported. The proposed methodology can be extended to
      any thiolated surface for the development of smart biomaterials for innovative
      approaches in regenerative medicine. 

PMID- 24443821
TI  - Study on the efficiency and interaction mechanism of a decapeptide inhibitor of
      beta-amyloid aggregation.
AB  - This paper reports an active decapeptide inhibitor (RR: RYYAAFFARR) of beta
      amyloid (Abeta(1-40)) aggregation. Traditional inhibitors target the hydrophobic
      core of Abeta (Abeta(16-20)) and were designed based on the single hydrophobic
      interaction. RR was designed to target an extended region (Abeta(11-23)), which
      contains three important regions of Abeta(1-40). RR exhibits stronger binding
      affinity for Abeta(1-40) (K(D) = 1.10 MUM) than the known beta-sheet breaker
      LPFFD (K(D) = 156 MUM). Our study shows that RR inhibited the fibrillation of
      Abeta(1-40) by nearly 75% at an equimolar concentration, and that a 1:4 ratio of
      Abeta(1-40)/ RR almost completely inhibited fibrillation. The interaction
      mechanism was also investigated by changing the ionic strength or the structure
      of RR. The results revealed that RR binds to Abeta(1-40) because of its strong
      affinity for Abeta(11-23), which is mainly driven by hydrophobic and
      electrostatic interactions and hydrogen bonding.

PMID- 24443820
TI  - Uptake and adherence of a self-directed internet-based mental health intervention
      with tailored e-mail reminders in senior high schools in Norway.
AB  - BACKGROUND: Internet-based cognitive behavioural therapy (ICBT) is a promising
      approach to the prevention and reduction of depressive symptoms among
      adolescents. This study aimed to evaluate the feasibility and efficacy of
      disseminating a self-directed internet-based mental health intervention (MoodGYM)
      in senior high schools. It also sought to investigate possible effects of
      tailored and weekly e-mail reminders on initial uptake and adherence to the
      intervention. METHOD: A baseline survey was conducted in four senior high schools
      in two Norwegian municipalities (n = 1337). 52.8% (707/1337) of the students
      consented to further participation in the trial and were randomly allocated to
      one of three MoodGYM intervention groups (tailored weekly e-mail reminder (n =
      175), standardized weekly e-mail reminder (n = 176 ) or no e-mail reminder (n =
      175)) or a waitlist control group (n = 180). We tested for effects of the
      intervention on depression and self-esteem using multivariate analysis of
      variance, effects of tailored e-mail and self-reported current need of help on
      initial uptake of the intervention using logistic regression and the effect of
      weekly e-mails on adherence using ordinal regression. RESULTS: There was
      substantial non-participation from the intervention, with only 8.5% (45/527)
      participants logging on to MoodGYM, and few proceeding beyond the first part of
      the programme. No significant effect on depression or self-esteem was found among
      the sample as a whole or among participants with elevated depression scores at
      baseline. Having a higher average grade in senior high school predicted initial
      uptake of the intervention, but tailored e-mail and self-reported current need of
      help did not. Weekly e-mail prompts did not predict adherence. The main reasons
      for non-use reported were lack of time/forgetting about it and doubt about the
      usefulness of the program. CONCLUSION: Overall, disseminating a self-directed
      internet-based intervention to a school population proved difficult despite steps
      taken to reduce barriers in terms of tailoring feedback and dispatching weekly e
      mail reminders. Providing mental health interventions within the school
      environment is likely to ensure better uptake among senior high school students,
      but there is a need to effectively communicate that such programmes can be
      helpful. TRIAL REGISTRATION: The trial was registered retrospectively as
      ACTRN12612001106820.

PMID- 24443822
TI  - Presuming the influence of the media: teenagers' constructions of gender identity
      through sexual/romantic relationships and alcohol consumption.
AB  - Using empirical data from group discussions and in-depth interviews with 13 to 15
      year olds in Scotland, this study explores how teenagers' alcohol drinking and
      sexual/romantic relationships were shaped by their quest for appropriate gendered
      identities. In this, they acknowledged the influence of the media, but primarily
      in relation to others, not to themselves, thereby supporting Milkie's 'presumed
      media influence' theory. Media portrayals of romantic/sexual relationships
      appeared to influence teenagers' constructions of gender-appropriate sexual
      behaviour more than did media portrayals of drinking behaviour, perhaps because
      the teenagers had more firsthand experience of observing drinking than of
      observing sexual relationships. Presumed media influence may be less influential
      if one has experience of the behaviour portrayed. Drinking and sexual behaviour
      were highly interrelated: sexual negotiation and activities were reportedly often
      accompanied by drinking. For teenagers, being drunk or, importantly, pretending
      to be drunk, may be a useful way to try out what they perceived to be gender
      appropriate identities. In sum, teenagers' drinking and sexual/romantic
      relationships are primary ways in which they do gender and the media's influence
      on their perceptions of appropriate gendered behaviour is mediated through peer
      relationships. 

PMID- 24443823
TI  - Associations between maternal level of education and occupational status with
      placental glucocorticoid regeneration and sensitivity.
AB  - OBJECTIVES: Low socio-economic status (SES) is associated with increased disease
      risk in the involved and the next generation. The effects of low maternal SES on
      the offspring may be initiated prenatally. We hypothesized that fetoplacental
      glucocorticoid exposure might mediate the links. We examined associations between
      maternal level of education and occupational status (used as indices of SES) and
      placental expression of genes involved in glucocorticoid exposure and transfer
      between the mother and foetus. DESIGN AND PATIENTS: Placental biopsies were
      obtained from 67 healthy women (age 32.2 +/- 5.3 years) with singleton, term
      pregnancies without obstetric complications who participated in a prospective
      Prediction and Prevention of Preeclampsia (PREDO) study. MEASURES: Level of
      education was self-reported, and occupational status was extracted from hospital
      records. Relative glucocorticoid receptor (GR; NR3C1), mineralocorticoid receptor
      (MR; NR3C2) and 11-beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2
      (HSD11B2) mRNA levels were quantified by real-time PCR. RESULTS: Placental GR and
      HSD11B1 expression increased with decreasing maternal education (unadjusted P
      values for linear trend = 0.04 and 0.02 and adjusted P-values = 0.06 and 0.09,
      respectively). Mothers with primary/secondary education had 52.9% (95% CI, 6.2
      99.6, P = 0.03, adjusted P = 0.05) and 79.6% (95% CI, 6.5-153.6, P = 0.03,
      adjusted P = 0.09) higher GR and HSD11B1 mRNA levels compared with mothers with
      tertiary education. There were no other significant associations. CONCLUSIONS:
      Lower maternal level of education is associated with increased placental GR and
      HSD11B1 gene expression. This combination may regenerate active glucocorticoids
      in placenta and increase placental sensitivity to glucocorticoids, potentially
      leading to greater placental and foetal glucocorticoid exposure.

PMID- 24443824
TI  - Eliminating malaria in Malaysia: the role of partnerships between the public and
      commercial sectors in Sabah.
AB  - BACKGROUND: Countries in the Asia Pacific region have made great progress in the
      fight against malaria; several are rapidly approaching elimination. However,
      malaria control programmes operating in elimination settings face substantial
      challenges, particularly around mobile migrant populations, access to remote
      areas and the diversity of vectors with varying biting and breeding behaviours.
      These challenges can be addressed through subnational collaborations with
      commercial partners, such as mining or plantation companies, that can conduct or
      support malaria control activities to cover employees. Such partnerships can be a
      useful tool for accessing high-risk populations and supporting malaria
      elimination goals. METHODS: This observational qualitative case study employed
      semi-structured key informant interviews to describe partnerships between the
      Malaysian Malaria Control Programme (MCP), and private palm oil, rubber and
      acacia plantations in the state of Sabah. Semi-structured interview guides were
      used to examine resource commitments, incentives, challenges, and successes of
      the collaborations. RESULTS: Interviews with workers from private plantations and
      the state of Sabah MCP indicated that partnerships with the commercial sector had
      contributed to decreases in incidence at plantation sites since 1991. Several
      plantations contribute financial and human resources toward malaria control
      efforts and all plantations frequently communicate with the MCP to help monitor
      the malaria situation on-site. Management of partnerships between private
      corporations and government entities can be challenging, as prioritization of
      malaria control may change with annual profits or arrival of new management.
      CONCLUSIONS: Partnering with the commercial sector has been an essential
      operational strategy to support malaria elimination in Sabah. The successes of
      these partnerships rely on a common understanding that elimination will be a
      mutually beneficial outcome for employers and the general public. Best practices
      included consistent communication, developing government-staffed subsector
      offices for malaria control on-site, engaging commercial plantations to provide
      financial and human resources for malaria control activities, and the development
      of new worker screening programmes. The successes and challenges associated with
      partnerships between the public and commercial sector can serve as an example for
      other malaria-eliminating countries with large plantation sectors, and may also
      be applied to other sectors that employ migrant workers or have commercial
      enterprises in hard to reach areas.

PMID- 24443825
TI  - A registered nurse refresher course: serving the community.
AB  - The Texas Board of Nursing recognizes that nurses may interrupt practice or
      change practice settings throughout their career and requires experienced nurses
      who have not practiced in more than 4 years to take a refresher course. In
      response to community requests for a local option for inactive nurses to reenter
      practice, the Department of Lifelong Learning in the university's school of
      nursing launched an RN refresher course in summer 2010. This article describes
      the scope of the RN refresher course, program costs, and future endeavors. More
      importantly, the article describes the nurses who are returning to nursing
      practice, including their age range, educational preparation, and length of time
      out of practice. Steady growth in enrollment, expanding clinical affiliations in
      the local area and selected areas throughout the state, and positive employment
      outcomes have facilitated course sustainment and growth.

PMID- 24443826
TI  - Comorbidity is an independent prognostic factor in women with uterine corpus
      cancer: a nationwide cohort study.
AB  - OBJECTIVE: To determine whether comorbidity independently affects overall
      survival in women with uterine corpus cancer. DESIGN: Cohort study. SETTING:
      Denmark. STUDY POPULATION: A total of 4244 patients registered in the Danish
      Gynecologic Cancer database with uterine corpus cancer from 1 January 2005 until
      13 October 2011. METHODS: All patients included in the study were assigned a
      comorbidity score according to the Charlson Comorbidity Index. Multivariate
      survival analyses were performed to investigate the prognostic impact of
      comorbidity adjusting for known prognostic factors. As performance status might
      capture the prognostic impact of comorbidity and because information on the
      variable grade was missing in some special histological subtypes, we included
      different models in the multivariate analyses with and without PS and grade,
      respectively. MAIN OUTCOME MEASURES: Overall survival. RESULTS: Univariate
      survival analysis showed a significant (p < 0.001) negative association between
      increasing level of comorbidity and overall survival. Multivariate analyses
      adjusting for other prognostic factors showed that comorbidity is a significant
      independent prognostic factor with hazard ratios ranging from 1.27 to 1.42 in
      mild, 1.69 to 1.74 in moderate, and 1.72 to 2.48 in severe comorbidity.
      Performance status was independently associated to overall survival and was found
      to slightly reduce the prognostic impact of comorbidity. CONCLUSION: Comorbidity
      is an independent prognostic factor in uterine corpus cancer and increasing
      levels of comorbidity are associated with shorter survival.

PMID- 24443827
TI  - Extensive brain structural network abnormality in first-episode treatment-naive
      patients with schizophrenia: morphometrical and covariation study.
AB  - BACKGROUND: Alterations in gray matter (GM) are commonly observed in
      schizophrenia. Accumulating studies suggest that the brain changes associated
      with schizophrenia are distributed rather than focal, involving interconnected
      networks of areas as opposed to single regions. In the current study we aimed to
      explore GM volume (GMV) changes in a relatively large sample of treatment-naive
      first-episode schizophrenia (FES) patients using optimized voxel-based
      morphometry (VBM) and covariation analysis. METHOD: High-resolution T1-weighted
      images were obtained using 3.0-T magnetic resonance imaging (MRI) from 86 first
      episode drug-naive patients with schizophrenia and 86 age- and gender-matched
      healthy volunteers. Symptom severity was evaluated using the Positive and
      Negative Syndrome Scale (PANSS). GMV was assessed using optimized VBM and in 16
      regions of interest (ROIs), selected on the basis of a previous meta-analysis.
      The relationships between GMVs in the ROIs were examined using an analysis of
      covariance (ANCOVA). RESULTS: The VBM analysis revealed that first-episode
      patients showed reduced GMV in the hippocampus bilaterally. The ROI analysis
      identified reductions in GMV in the left inferior frontal gyrus, bilateral
      hippocampus and right thalamus. The ANCOVA revealed different patterns of
      regional GMV correlations in patients and controls, including of inter- and intra
      insula, inter-amygdala and insula-postcentral gyrus connections. CONCLUSIONS:
      Schizophrenia involves regional reductions in GMV and changes in GMV covariance
      in the insula, amygdala and postcentral gyrus. These findings were evident at the
      onset of the disorder, before treatment, and therefore cannot be attributable to
      the effects of chronic illness progression or medication.

PMID- 24443828
TI  - Antibacterial activities of coagulase-negative staphylococci from bovine teat
      apex skin and their inhibitory effect on mastitis-related pathogens.
AB  - AIMS: To explore antibacterial activities of coagulase-negative staphylococci
      (CoNS) from teat apices of dairy cows towards mastitis-causing pathogens. METHODS
      AND RESULTS: Of 254 CoNS, 38 displayed bacteriocin-like activity after a first
      screening. Seven of these strains displayed activity against at least one
      mastitis-related pathogen (Streptococcus uberis, Streptococcus dysgalactiae and
      Staphylococcus aureus). Staphylococcus chromogenes L217 displayed the strongest
      inhibitory effect, being active against all tested mastitis-related pathogens and
      most tested CoNS. Based on cation exchange and reversed-phase chromatography, in
      addition to N-terminal Edman degradation and PCR, the antibacterial peptide was
      identified as a nukacin-type bacteriocin and named nukacin L217. Although
      staphylococcal bacteriocins are generally found in the cell-free supernatants of
      liquid cultures, Staph. chromogenes L217 only led to detectable activity when
      grown on agar medium. CONCLUSIONS: Bacteriocin-like activities are not uncommon
      among CoNS from teat apices and may inhibit mastitis-causing pathogens, as found
      for nukacin L217 production by Staph. chromogenes L217. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Nukacin L217 is the first identified bacteriocin of the species
      Staph. chromogenes and displays unusual production kinetics, that is, requiring
      surface growth of its producer. The fact that nukacins are produced by different
      CoNS species suggests a role in the teat skin ecosystem.

PMID- 24443829
TI  - A descriptive cross-sectional international study to explore current practices in
      the assessment, prevention and treatment of skin tears.
AB  - This study presents the results of a descriptive, cross-sectional, online
      international survey in order to explore current practices in the assessment,
      prediction, prevention and treatment of skin tears (STs). A total of 1127 health
      care providers (HCP) from 16 countries completed the survey. The majority of the
      respondents (69.6%, n = 695) reported problems with the current methods for the
      assessment and documentation of STs with an overwhelming majority (89.5%, n =
      891) favouring the development of a simplified method of assessment. Respondents
      ranked equipment injury during patient transfer and falls as the main causes of
      STs. The majority of the samples indicated that they used non-adhesive dressings
      (35.89%, n = 322) to treat a ST, with the use of protective clothing being the
      most common method of prevention. The results of this study led to the
      establishment of a consensus document, classification system and a tool kit for
      use by practitioners. The authors believe that this survey was an important first
      step in raising the global awareness of STs and to stimulate discussion and
      research of these complex acute wounds.

PMID- 24443830
TI  - A comparison of adding liraglutide versus a single daily dose of insulin aspart
      to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON).
AB  - AIM: Two treatment strategies were compared in patients with type 2 diabetes
      (T2DM) on basal insulin requiring intensification: addition of once-daily (OD)
      liraglutide (Lira) or OD insulin aspart (IAsp) with largest meal. METHODS:
      Subjects completing 104 weeks (52-week main trial BEGIN ONCE-LONG + 52-week
      extension) on insulin degludec (IDeg) OD + metformin with HbA1c >= 7.0% (>=53
      mmol/mol) were randomized to IDeg+Lira [n = 88, mean HbA1c: 7.7% (61 mmol/mol)]
      or IDeg+IAsp (n = 89, mean HbA1c: 7.7%) for 26 weeks, continuing metformin.
      Subjects completing 104 weeks with HbA1c <7.0% continued IDeg + metformin in a
      third, non-randomized arm (n = 236). RESULTS: IDeg+Lira reduced HbA1c (-0.74%
      points) significantly more than IDeg+IAsp (-0.39%-points); estimated treatment
      difference (ETD) (IDeg+Lira-IDeg+IAsp) -0.32%-points (95% CI -0.53; -0.12); p =
      0.0024. More IDeg+Lira (49.4%) than IDeg+IAsp (7.2%) subjects achieved HbA1c
      <7.0% without confirmed hypoglycaemia [plasma glucose <3.1 mmol/l (<56 mg/dl) or
      severe hypoglycaemia) and without weight gain; estimated odds ratio
      (IDeg+Lira/IDeg+IAsp) 13.79 (95% CI 5.24; 36.28); p < 0.0001. IDeg+Lira subjects
      had significantly less confirmed and nocturnal confirmed hypoglycaemia, and
      significantly greater weight loss (-2.8 kg) versus IDeg+IAsp (+0.9 kg); ETD
      (IDeg+Lira-IDeg+IAsp) -3.75 kg (95% CI -4.70; -2.79); p < 0.0001. Other than more
      gastrointestinal side effects with IDeg+Lira, no safety differences occurred.
      Durability of IDeg was established in the non-randomized arm, as mean HbA1c
      remained <7.0% [mean 6.5% (48 mmol/mol) at end-of-trial]. CONCLUSIONS: IDeg+Lira
      improved long-term glycaemic control, with weight loss and less hypoglycaemia
      versus adding a single daily dose of IAsp in patients with T2DM inadequately
      controlled with IDeg + metformin.

PMID- 24443831
TI  - Patterns of postpartum depot medroxyprogesterone administration among low-income
      mothers.
AB  - BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is often administered
      immediately postpartum to reduce the risk of short-interval repeat or unintended
      pregnancies, but little is known about the actual patterns of postpartum DMPA
      use. This article examines the patterns of DMPA administered among low-income new
      mothers in an upstate New York State community. METHODS: Mothers attending urban
      pediatric practices (births 2009-2011) completed a mailed survey approximately 5
      months after delivery. Among 83 survey items were questions about breastfeeding
      and timing of DMPA receipt. RESULTS: Unintended pregnancy was reported by 48.8%
      of the subjects. Their deliveries occurred across four local hospitals. Among the
      31.3% of subjects who received postpartum DMPA, 62.6% received it prior to
      hospital discharge. Those receiving in-hospital DMPA (n=127) were significantly
      more likely than other mothers to be black, older, urban dwelling, non-high
      school graduates, multiparous, and planning to formula feed. Administration
      patterns differed by hospital. CONCLUSIONS: This study of postpartum DMPA
      administration among a convenience sample of low-income mothers demonstrated
      rates of 26% overall, but there was between-hospital variability. Additional
      study may identify approaches to ensure timely administration to appropriate
      candidates.

PMID- 24443832
TI  - Physical and sexual intimate partner violence, women's health and children's
      behavioural functioning: entry analysis of a seven-year prospective study.
AB  - AIMS AND OBJECTIVES: To increase knowledge of physical and sexual intimate
      partner violence against women, its impact on women's health and children's
      behavioural functioning. BACKGROUND: Physical assault and sexual assault
      frequently co-occur. Women who experience both physical and sexual violence are
      at risk of poorer health outcomes than women who experience only physical
      violence. The behavioural functioning of children of women who experience partner
      violence may be adversely affected. DESIGN: Cross-sectional, using baseline data
      from a seven-year prospective study. METHODS: Data related to severity of abuse
      (both physical and sexual) and the outcome measures of maternal (n = 300) mental
      health measures, risk of lethality, chronic pain and child (n = 300) behavioural
      functioning were analysed. RESULTS: Higher physical abuse scores were
      significantly correlated with higher sexual abuse scores, and higher levels of
      physical abuse were associated with higher maternal anxiety and higher child
      externalisation scores. Higher levels of sexual abuse were associated with higher
      maternal somatisation and post-traumatic stress disorder symptoms and higher
      child internalisation scores and total problems. CONCLUSIONS: These initial
      findings suggest that children have behavioural functioning and coping that is
      closely related to their mothers' functioning, which is based on the type of
      abuse experienced by the mothers. As we gain a greater understanding of these
      issues, we will be better able to develop effective policies and therapeutic
      interventions to help abused women and their children. RELEVANCE TO CLINICAL
      PRACTICE: Findings for the mental health functioning of women participating in
      this study add to the overwhelming evidence for the importance of screening for
      partner violence when women present for health care and for the need for
      effective assistance services for women who have or are currently experiencing
      partner violence. They also support emerging research that indicates the great
      need to provide effective services for the children of abused women.

PMID- 24443833
TI  - Constituents of essential oils from the leaves, stem barks and resins of Canarium
      parvum Leen., and Canarium tramdenanum Dai et Yakovl. (Burseracea) grown in
      Vietnam.
AB  - The chemical constituents of essential oils from the leaf, stem bark and resins
      of Canarium parvum Leen., and Canarium tramdenanum Dai et Yakovl. (Burseracea)
      grown in Vietnam are being reported. The hydrodistilled oils were analysed for
      their chemical constituents by means of gas chromatography-flame ionisation
      detector and gas chromatography coupled with mass spectrometry. The main
      compounds of C. parvum were beta-caryophyllene (18.7%), (E)-beta-ocimene (12.9%),
      (Z)-beta-ocimene (11.9%), germacrene D (8.8%) and alpha-humulene (8.4%) in the
      leaf; beta-caryophyllene (30.4%), alpha-copaene (20.5%) and (E)-beta-ocimene
      (7.7%) in the stem. However, germacrene D (23.2%), alpha-amorphene (14.9%), alpha
      copaene (9.8%) and beta-elemene (8.6%) were present in the resin. The leaf of C.
      tramdenanum comprises beta-caryophyllene (16.8%), alpha-phellandrene (15.9%),
      gamma-elemene (13.1%) and limonene (11.8%), while limonene (25.7%), alpha
      phellandrene (21.7%), alpha-pinene (12.3%) and beta-caryophyllene (10.9%) were
      present in the stem. However, delta-elemene (14.6%) and bulnesol (16.0%) are the
      main constituents in the resin. 

PMID- 24443835
TI  - Retrieval of bilingual autobiographical memories: effects of cue language and cue
      imageability.
AB  - An important issue in theories of bilingual autobiographical memory is whether
      linguistically encoded memories are represented in language-specific stores or in
      a common language-independent store. Previous research has found that
      autobiographical memory retrieval is facilitated when the language of the cue is
      the same as the language of encoding, consistent with language-specific memory
      stores. The present study examined whether this language congruency effect is
      influenced by cue imageability. Danish-English bilinguals retrieved
      autobiographical memories in response to Danish and English high- or low
      imageability cues. Retrieval latencies were shorter to Danish than English cues
      and shorter to high- than low-imageability cues. Importantly, the cue language
      effect was stronger for low-than high-imageability cues. To examine the
      relationship between cue language and the language of internal retrieval,
      participants identified the language in which the memories were internally
      retrieved. More memories were retrieved when the cue language was the same as the
      internal language than when the cue was in the other language, and more memories
      were identified as being internally retrieved in Danish than English, regardless
      of the cue language. These results provide further evidence for language
      congruency effects in bilingual memory and suggest that this effect is influenced
      by cue imageability. 

PMID- 24443834
TI  - Altered lipid composition in Streptococcus pneumoniae cpoA mutants.
AB  - BACKGROUND: Penicillin-resistance in Streptococcus pneumoniae is mainly due to
      alterations in genes encoding the target enzymes for beta-lactams, the penicillin
      binding proteins (PBPs). However, non-PBP genes are altered in beta-lactam
      resistant laboratory mutants and confer decreased susceptibility to beta-lactam
      antibiotics. Two piperacillin resistant laboratory mutants of Streptococcus
      pneumoniae R6 contain mutations in the putative glycosyltransferase gene cpoA.
      The CpoA gene is part of an operon including another putative glycosyltransferase
      gene spr0982, both of which being homologous to glycolipid synthases present in
      other Gram-positive bacteria. RESULTS: We now show that the cpoA mutants as well
      as a cpoA deletion mutant are defective in the synthesis of galactosyl-glucosyl
      diacylglycerol (GalGlcDAG) in vivo consistent with the in vitro function of CpoA
      as alpha-GalGlcDAG synthase as shown previously. In addition, the proportion of
      phosphatidylglycerol increased relative to cardiolipin in cpoA mutants. Moreover,
      cpoA mutants are more susceptible to acidic stress, have an increased requirement
      for Mg(2+) at low pH, reveal a higher resistance to lysis inducing conditions and
      are hypersensitive to bacitracin. CONCLUSIONS: The data show that deficiency of
      the major glycolipid GalGlcDAG causes a pleitotropic phenotype of cpoA mutant
      cells consistent with severe membrane alterations. We suggest that the cpoA
      mutations selected with piperacillin are directed against the lytic response
      induced by the beta-lactam antibiotic.

PMID- 24443836
TI  - Hierarchical SnO2 nanostructures made of intermingled ultrathin nanosheets for
      environmental remediation, smart gas sensor, and supercapacitor applications.
AB  - In this paper, the hierarchical SnO2 nanostructures (HTNs) were prepared by a
      facile hydrothermal process. The prepared HTNs were characterized in detail by
      various analytical techniques that reveal the well-crystallinity with tetragonal
      rutile structure of SnO2 for the as-prepared material. By detailed experiments,
      interestingly, it was observed that the shapes and sizes of as-prepared HTNs
      could be tailored by varying the precursor concentration and reaction time. The
      synthesized HTNs were used as the efficient photocatalysts for the photocatalytic
      degradation of methylene blue (MB) under light illumination which showed almost
      complete degradation (~99%) of MB dye in 20 min. The observed degradation for MB
      dye was higher than other commonly used dyes, i.e. methyl orange (MO; 96% in 50
      min) and Rhodamine B (RhB; 97% in 40 min.). Further, the prepared HTNs were used
      as the effective gas sensing material to examine a series of volatile gases, such
      as ethanol, ammonia, benzene, acetone, toluene, methanol, diethyl ether, and
      methanol. By the detailed experiments, it was observed that the prepared HTNs
      exhibited tremendous gas sensing performance toward ethanol. Finally, because of
      the unique morphology and the fast ion and electron transfer characteristics, the
      prepared HTNs show excellent supercapacitor performances. 

PMID- 24443837
TI  - Protective effects of flavonol isoquercitrin, against 6-hydroxy dopamine (6-OHDA)
      induced toxicity in PC12 cells.
AB  - BACKGROUND: Free radicals-induced neurodegeneration is one of the many causes of
      Parkinson's disease (PD). This study investigated the neuroprotective effects of
      flavonol isoquercitrin against toxicity induced by 6-hydroxy-dopamine (6-OHDA) in
      rat pheochromocytoma (PC12) cells. METHODS: PC12 cells were pretreated with
      different concentrations of isoquercitrin for 4, 8 and 12 hours and incubated
      with 6-OHDA for 24 hours to induce oxidative cell damage. RESULTS: A significant
      cytoprotective activity was observed in isoquercitrin pre-treated cells in a dose
      dependent manner. There was a significant increase (P < 0.01) in the antioxidant
      enzymes namely superoxide dismutase, catalase, glutathione peroxidase, and
      glutathione in isoquercitrin pretreated cells compared to cells incubated with 6
      OHDA alone. Isoquercitrin significantly reduced (P < 0.01) lipid peroxidation in
      6-OHDA treated cells. These results suggested that isoquercitrin protects PC 12
      cells against 6-OHDA-induced oxidative stress. CONCLUSIONS: The present study
      suggests the protective role of isoquercitrin on 6-hydroxydopamine-induced
      toxicity by virtue of its antioxidant potential. Isoquercitrin could be a
      potential therapeutic agent against neurodegeneration in Parkinson's disease.

PMID- 24443838
TI  - The experimental study on the treatment of cytokine-induced killer cells combined
      with EGFR monoclonal antibody against gastric cancer.
AB  - AIMS: To investigate the antitumor activity of cytokine-induced killer (CIK)
      cells combined with epidermal growth factor receptor (EGFR) monoclonal antibody
      (mAb) against gastric cancer cell line SGC7901. MATERIALS AND METHODS:
      Immunocytochemistry assay was performed to detect the expression of EGFR in
      SGC7901 cell lines. The cytotoxicity activity of CIK cells combined with EGFR mAb
      was analyzed by the (51)Cr release assay. Then, the comparison of the
      cytotoxicity activity between CIK cells combined with EGFR mAb and CIK cells
      combined with CD3 mAb and CIK cells was conducted. Antitumor activity of CIK
      cells combined with EGFR mAb in vivo was analyzed by tumor growth assay and tumor
      reduction assay. RESULTS: The cell lysis rate of CIK cells combined with EGFR mAb
      was higher than those of CIK cells combined with CD3 mAb and CIK cells only
      (p<0.05). The lysis rates of the latter two groups were not different. The
      antitumor activity of CIK cells combined with EGFR mAb was higher than those of
      other groups in vivo (p<0.05). CONCLUSION: It was suggested in the current study
      that EGFR mAb could enhance the antitumor ability of CIK cells to bind and kill
      the gastric cancer cells in vitro and in vivo.

PMID- 24443839
TI  - The calcium sensor GhCaM7 promotes cotton fiber elongation by modulating reactive
      oxygen species (ROS) production.
AB  - Fiber elongation is the key determinant of fiber quality and output in cotton
      (Gossypium hirsutum). Although expression profiling and functional genomics
      provide some data, the mechanism of fiber development is still not well
      understood. Here, a gene encoding a calcium sensor, GhCaM7, was isolated based on
      its high expression level relative to other GhCaMs in fiber cells at the fast
      elongation stage. The level of expression of GhCaM7 in the wild-type and the
      fuzzless/lintless mutant correspond to the presence and absence, respectively, of
      fiber initials. Overexpressing GhCaM7 promotes early fiber elongation, whereas
      GhCaM7 suppression by RNAi delays fiber initiation and inhibits fiber elongation.
      Reactive oxygen species (ROS) play important roles in early fiber development.
      ROS induced by exogenous hydrogen peroxide (H2 O2 ) and Ca(2+) starvation
      promotes early fiber elongation. GhCaM7 overexpression fiber cells show increased
      ROS concentrations compared with the wild-type, while GhCaM7 RNAi fiber cells
      have reduced concentrations. Furthermore, we show that H2 O2 enhances Ca(2+)
      influx into the fiber and feedback-regulates the expression of GhCaM7. We
      conclude that GhCaM7, Ca(2+) and ROS are three important regulators involved in
      early fiber elongation. GhCaM7 might modulate ROS production and act as a
      molecular link between Ca(2+) and ROS signal pathways in early fiber development.

PMID- 24443840
TI  - Terthiophene derivatives of cholesterol-based molecular gels and their sensing
      applications.
AB  - Three novel terthiophene derivatives of cholesterol (TtGC, TtLPC, TtDPC), of
      which the two building blocks are linked by a structure of glycine, l
      phenylalanine, or d-phenylalanine, respectively, were designed and prepared, and
      their gelation behaviors in 26 liquids were tested. It was demonstrated that the
      compounds show different gelation abilities with the variation of the linker
      structures even though the variation is small. FTIR, (1)H NMR, and UV-vis
      measurements revealed that intermolecular hydrogen bonding and van der Waals
      interaction are the main driving forces for the gel formation. As for TtDPC, CD
      and AFM measurements revealed that it aggregated into chiral structures of left
      helical feature in benzene. Importantly, the morphologies of the gel networks
      could be subtly adjusted via alteration of the gelator concentration. Considering
      the brightness in fluorescence and the unique micro/nanostructures of the gel
      networks, a fluorescent film (film 1) was fabricated by simple dip-coating of
      TtDPC/benzene solution (before gelation) onto a glass plate surface. Fluorescent
      studies demonstrated that the film is photochemically unstable. Two hours UV
      irradiation of the film results in film 2, which is almost fluorescent silence.
      However, the presence of HAc vapor or the vapors of some other volatile organic
      liquids induces new fluorescence emission, laying the foundation for creating a
      turn-on type fluorescent sensor of the organic vapors. Furthermore, as a new type
      of low-molecular-mass gelators (LMMGs), of which oligothiophene was employed as a
      building block, the present study has provided a possibility to explore the photo
      /electronic applications of oligothiophenes via a molecular gel strategy. 

PMID- 24443841
TI  - Neurofilaments as a plasma biomarker for ICU-acquired weakness: an observational
      pilot study.
AB  - INTRODUCTION: Early diagnosis of intensive care unit - acquired weakness (ICU-AW)
      using the current reference standard, that is, assessment of muscle strength, is
      often hampered due to impaired consciousness. Biological markers could solve this
      problem but have been scarcely investigated. We hypothesized that plasma levels
      of neurofilaments are elevated in ICU-AW and can diagnose ICU-AW before muscle
      strength assessment is possible. METHODS: For this prospective observational
      cohort study, neurofilament levels were measured using ELISA (NfHSMI35 antibody)
      in daily plasma samples (index test). When patients were awake and attentive, ICU
      AW was diagnosed using the Medical Research Council scale (reference standard).
      Differences and discriminative power (using the area under the receiver operating
      characteristic curve; AUC) of highest and cumulative (calculated using the area
      under the neurofilament curve) neurofilament levels were investigated in relation
      to the moment of muscle strength assessment for each patient. RESULTS: Both the
      index test and reference standard were available for 77 ICU patients. A total of
      18 patients (23%) fulfilled the clinical criteria for ICU-AW. Peak neurofilament
      levels were higher in patients with ICU-AW and had good discriminative power
      (AUC: 0.85; 95% CI: 0.72 to 0.97). However, neurofilament levels did not peak
      before muscle strength assessment was possible. Highest or cumulative
      neurofilament levels measured before muscle strength assessment could not
      diagnose ICU-AW (AUC 0.59; 95% CI 0.37 to 0.80 and AUC 0.57; 95% CI 0.32 to 0.81,
      respectively). CONCLUSIONS: Plasma neurofilament levels are raised in ICU-AW and
      may serve as a biological marker for ICU-AW. However, our study suggests that an
      early diagnosis of ICU-AW, before muscle strength assessment, is not possible
      using neurofilament levels in plasma.

PMID- 24443842
TI  - A huge malignant solitary fibrous tumor of kidney: case report and review of the
      literature.
AB  - Solitary fibrous tumor (SFT) is a spindle cell neoplasm that rarely occurs in the
      kidney. Malignant SFT of the kidney is particularly rare. Here, we report a 66
      year old woman with a right flank mass that has been proved clinically and
      radiographically. Grossly, the largest diameter of the mass were measured up to
      23 cm, was poorly circumscribed. Approximately 80% of the neoplasm consisted of
      hyperchromatic and pleomorphic spindled cells surrounding staghornlike blood
      vessels. Tumor cells frequently had mitoses and necrosis. However, the remainder
      of the mass was composed of haphazard, storiform or short fascicular arrangements
      of spindle cells in a loose myxoid to fibrous stroma. Immunohistochemically, we
      observed diffusely strong CD34 staining and an 85% Ki-67 proliferative index. The
      tumor partly showed negative CD34 and a 20% proliferative index. To our
      knowledge, this is the largest malignant renal SFT in the reported literatures
      and shows an obviously high proliferative index. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1603694556107408.

PMID- 24443843
TI  - Reversible anion-induced cross-linking of well-defined calix[4]pyrrole-containing
      copolymers.
AB  - Reversible addition/fragmentation chain-transfer polymerization is used to
      generate a calix[4]pyrrole methacrylate-derived copolymer. The material is found
      to undergo supramolecular cross-linking upon exposure to select dianionic species
      (e.g., pyrophosphate and terephthalate salts), altering the viscoelastic
      properties of the copolymer in solution and in the solid state. The copolymeric
      material is also used for selective differentiation of mono- and bis-anions under
      conditions of liquid/liquid extraction. 

PMID- 24443844
TI  - Optical tweezers analysis of DNA-protein complexes.

PMID- 24443846
TI  - High relapse rate of T cell acute lymphoblastic leukemia in adults treated with
      Hyper-CVAD chemotherapy in Sweden.
AB  - BACKGROUND: Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL)
      and aggressive lymphomas. This multicenter, population-based study assessed the
      efficacy of Hyper-CVAD as first-line therapy in patients with T-cell ALL (T-ALL).
      PATIENTS AND METHODS: Between October 2002 and September 2006, 24 patients were
      diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.
      RESULTS: The median age was 32 yr (range 18-72 yr). Complete remission (CR) was
      obtained in 17 of 19 (89%) patients, and the treatment was relatively well
      tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high
      risk disease and was performed in four patients upfront. Two- and 5-yr leukemia
      free survivals (LFS) in 17 patients with CR achievement were identical, at 29%
      (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in
      whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5
      yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95%
      CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse
      occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated
      with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age >=35 yr
      influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).
      CONCLUSIONS: Hyper-CVAD treatment resulted in a high CR rate and appeared safe,
      but it showed poor efficacy at preventing relapse. Therefore, this treatment is
      no longer recommended for adults with T-ALL in Sweden.

PMID- 24443845
TI  - Do weight management programmes delivered at professional football clubs attract
      and engage high risk men? A mixed-methods study.
AB  - BACKGROUND: The prevalence of obesity in men in the UK is amongst the highest in
      Europe but men are less likely than women to use existing weight loss programmes.
      Developing weight management programmes which are appealing and acceptable to men
      is a public health priority. Football Fans in Training (FFIT), a men-only weight
      management programme delivered to groups of men at top professional football
      clubs, encourages men to lose weight by working with, not against, cultural
      ideals of masculinity. To inform further development of interventions in football
      club settings, the current study explored who is attracted to FFIT and why
      overweight/obese men choose to take part. METHODS: A mixed-methods study
      analysing baseline data on 747 men aged 35-65 years with BMI >= 28 kg/m2 who were
      participants in a randomised controlled trial of FFIT, and data from 13 focus
      group discussions with 63 men who had attended the programme. RESULTS:
      Objectively-measured mean body mass index was 35.3 kg/m2 (sd 4.9). Overall over
      90% of participants were at very high or extremely high risk of future ill
      health. Around three-quarters of participants in all age groups were at 'very
      high' risk of type 2 diabetes, hypertension and cardiovascular disease (72%, 73%
      and 80% of men aged 35-44, 45-54 and 55-64 years respectively). A further 21%,
      16% and 13% were at 'extremely high' risk. Qualitative data revealed that the
      powerful 'draw' of the football club attracted men otherwise reluctant to attend
      existing weight management programmes. The location and style of delivery of
      early FFIT sessions fostered team spirit; men appreciated being with others 'like
      them' and the opportunity to undertake weight management in circumstances that
      enhanced physical and symbolic proximity to something they valued highly, the
      football club. CONCLUSIONS: The delivery of a weight management intervention via
      professional football clubs attracted men at high risk of ill-health. The setting
      enabled men to join a weight management programme in circumstances that felt
      'right' rather than threatening to themselves as men. FFIT is an example of how
      to facilitate health promotion activities in a way that is consistent with,
      rather than challenging to, common ideals of masculinity.

PMID- 24443847
TI  - The commodification of patient opinion: the digital patient experience economy in
      the age of big data.
AB  - As part of the digital health phenomenon, a plethora of interactive digital media
      platforms have been established in recent years to elicit lay people's
      experiences of illness and health care. The overt function of these platforms is
      to provide forums where patients and caregivers can share their experiences with
      others, benefit from the support and knowledge of other users and contribute to
      large aggregated data archives as part of developing better medical treatments
      and services and conducting medical research. However, what may not always be
      readily apparent to the users of these platforms are the growing commercial uses
      by many of the platforms' owners of the data they contribute. This article
      examines this phenomenon of what I term 'the digital patient experience economy'.
      Such aspects of this economy as prosumption (the combination of content
      consumption and production that is characteristic of the use of Web 2.0
      technologies), the valorising of big data, the discourse and ethic of sharing and
      the commercialisation of affective labour are discussed. It is argued that via
      these online platforms patients' opinions and experiences may be expressed in
      more diverse and accessible forums than ever before, but simultaneously they have
      become exploited in novel ways.

PMID- 24443849
TI  - Is there a case for mandating influenza vaccination in healthcare workers?

PMID- 24443848
TI  - Building the bacterial orisome: high-affinity DnaA recognition plays a role in
      setting the conformation of oriC DNA.
AB  - During assembly of the E. coli pre-replicative complex (pre-RC), initiator DnaA
      oligomers are nucleated from three widely separated high-affinity DnaA
      recognition sites in oriC. Oligomer assembly is then guided by low-affinity DnaA
      recognition sites, but is also regulated by a switch-like conformational change
      in oriC mediated by sequential binding of two DNA bending proteins, Fis and IHF,
      serving as inhibitor and activator respectively. Although their recognition sites
      are separated by up to 90 bp, Fis represses IHF binding and weak DnaA
      interactions until accumulating DnaA displaces Fis from oriC. It remains unclear
      whether high-affinity DnaA binding plays any role in Fis repression at a distance
      and it is also not known whether all high-affinity DnaA recognition sites play an
      equivalent role in oligomer formation. To examine these issues, we developed
      origin-selective recombineering methods to mutate E. coli chromosomal oriC. We
      found that, although oligomers were assembled in the absence of any individual
      high-affinity DnaA binding site, loss of DnaA binding at peripheral sites
      eliminated Fis repression, and made binding of both Fis and IHF essential. We
      propose a model in which interaction of DnaA molecules at high-affinity sites
      regulates oriC DNA conformation.

PMID- 24443850
TI  - New perspectives on airway management in acutely burned patients.

PMID- 24443851
TI  - The effects of general anaesthesia on memory in children: a comparison between
      propofol and sevoflurane.
AB  - We studied the effects of general anaesthesia on memory 7 days and 3 months
      following elective hernia surgery. Sixty children aged between 7 and 13 years
      were randomly allocated to receive either propofol or sevoflurane. Memory was
      classified into immediate, short-term and long-term memory and assessed using the
      Wechsler Memory Scale-Propofol impaired short-term memory 7 days postoperatively
      compared with pre-operative values (image recalling: p = 0.02, figure
      recognition: p = 0.01, visual reproduction: p = 0.03) but recovered to baseline
      levels 3 months following surgery. Neither general anaesthetic affected immediate
      or long-term memory. We conclude that propofol impairs short-term memory
      postoperatively in children.

PMID- 24443852
TI  - A prospective multicentre observational study of adverse iatrogenic events and
      substandard care preceding intensive care unit admission (PREVENT).
AB  - We examined the current incidence, type, severity and preventability of
      iatrogenic events associated with intensive care unit admission in five hospitals
      in England. All unplanned adult admissions to intensive care units were
      prospectively reviewed over a continuous six-week period. In the week before
      admission, 76/280 patients (27%) experienced 104 iatrogenic events. The majority
      of iatrogenic events were categorised as medical (37%), drug (17%) or nursing
      events (17%). Seventy-seven per cent of the events were considered preventable
      and 80% caused or contributed to admission. Eleven events were thought to have
      contributed to a patient's death. The mean (SD) age of patients who had an event
      was greater (63 (21) years) than those who had not (57 (19) years, p = 0.023),
      and they had a longer median (IQR [range]) intensive care stay, 4 (1-8 [0-29])
      days vs 3 (1-5 [0-20]) days, respectively, p = 0.043.

PMID- 24443853
TI  - Near-fatal anaphylaxis caused by human serum albumin in fibrinogen and
      erythrocyte concentrates.
AB  - A 40-year-old man developed anaphylactic shock during surgical replacement of a
      prolapsed mitral valve during general anaesthesia and an attenuated reaction
      (Grade 2), three days later during a blood transfusion. Human serum albumin, a
      component of the fibrinogen concentrate used postoperatively with the erythrocyte
      concentrate, was identified as the trigger, confirmed by positive skin prick and
      intradermal tests. Any anaphylaxis during the peri-operative period should cause
      the clinician to perform allergy tests for identification of the culprit drug
      and, sometimes, culprit additive. Testing of human serum albumin, acting as
      hidden allergen, should be included, especially where there has been a blood
      transfusion.

PMID- 24443854
TI  - Leaking octopus.

PMID- 24443855
TI  - Anaesthetists' engagement in National Joint Registry data collection.

PMID- 24443856
TI  - Use of the GlideScope((r)) for double-lumen endobronchial intubation.

PMID- 24443857
TI  - A reply.

PMID- 24443858
TI  - Retrograde tracheal intubation for bleeding and fragmenting airway tumours.

PMID- 24443859
TI  - A reply.

PMID- 24443860
TI  - Intracuff pressures in ProSeal and Supreme airways.

PMID- 24443861
TI  - Epidural anaesthesia and analgesia for liver resection.

PMID- 24443862
TI  - Feedback for trainers in trouble.

PMID- 24443863
TI  - Preservative-free bicarbonate for epidural top-ups.

PMID- 24443864
TI  - Magnesium sulphate and postoperative agitation in children: an analgesic effect?

PMID- 24443865
TI  - A reply.

PMID- 24443866
TI  - Mephedrone-induced uvulitis.

PMID- 24443867
TI  - Desflurane vaporiser contamination.

PMID- 24443868
TI  - Co-administering diclofenac with intravenous paracetamol or Hartmann's solution.

PMID- 24443869
TI  - Serratus plane block - is a high volume of local anaesthetic needed?

PMID- 24443870
TI  - Precipitation reaction between vancomycin and Gelofusine((r)).

PMID- 24443871
TI  - A reply.

PMID- 24443872
TI  - When is an audit not an audit?

PMID- 24443873
TI  - The role of immunity in mosquito-induced attenuation of malaria virulence.
AB  - A recent study found that mosquito-transmitted (MT) lines of rodent malaria
      parasites elicit a more effective immune response than non-transmitted lines
      maintained by serial blood passage (non-MT), thereby causing lower parasite
      densities in the blood and less pathology to the host. The authors attribute
      these changes to higher diversity in expression of antigen-encoding genes in MT
      cf. non-MT lines. Alternative explanations that are equally parsimonious with
      these new data, and results from previous studies, suggest that this conclusion
      may be premature. 

PMID- 24443874
TI  - A longitudinal twin study of physical aggression during early childhood: evidence
      for a developmentally dynamic genome.
AB  - BACKGROUND: Physical aggression (PA) tends to have its onset in infancy and to
      increase rapidly in frequency. Very little is known about the genetic and
      environmental etiology of PA development during early childhood. We investigated
      the temporal pattern of genetic and environmental etiology of PA during this
      crucial developmental period. METHOD: Participants were 667 twin pairs, including
      254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec
      Newborn Twin Study. Maternal reports of PA were obtained from three waves of data
      at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky
      decomposition and linear latent growth curve model. RESULTS: The best-fitting
      Cholesky model revealed developmentally dynamic effects, mostly genetic
      attenuation and innovation. The contribution of genetic factors at 20 months
      substantially decreased over time, while new genetic effects appeared later on.
      The linear latent growth curve model revealed a significant moderate increase in
      PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors
      accounted for the variation in initial level and growth rate. Non-shared and
      shared environments had no effect on the stability, initial status and growth
      rate in PA. CONCLUSIONS: Genetic factors underlie PA frequency and stability
      during early childhood; they are also responsible for initial status and growth
      rate in PA. The contribution of shared environment is modest, and perhaps
      limited, as it appears only at 50 months. Future research should investigate the
      complex nature of these dynamic genetic factors through genetic-environment
      correlation (r GE) and interaction (G*E) analyses.

PMID- 24443875
TI  - Mapping the human toxome by systems toxicology.
AB  - Toxicity testing typically involves studying adverse health outcomes in animals
      subjected to high doses of toxicants with subsequent extrapolation to expected
      human responses at lower doses. The low-throughput of current toxicity testing
      approaches (which are largely the same for industrial chemicals, pesticides and
      drugs) has led to a backlog of more than 80,000 chemicals to which human beings
      are potentially exposed whose potential toxicity remains largely unknown.
      Employing new testing strategies that employ the use of predictive, high
      throughput cell-based assays (of human origin) to evaluate perturbations in key
      pathways, referred as pathways of toxicity, and to conduct targeted testing
      against those pathways, we can begin to greatly accelerate our ability to test
      the vast 'storehouses' of chemical compounds using a rational, risk-based
      approach to chemical prioritization and provide test results that are more
      predictive of human toxicity than current methods. The NIH Transformative
      Research Grant project Mapping the Human Toxome by Systems Toxicology aims at
      developing the tools for pathway mapping, annotation and validation as well as
      the respective knowledge base to share this information. 

PMID- 24443876
TI  - Changes in weight loss-related quality of life among type 2 diabetes mellitus
      patients treated with dapagliflozin.
AB  - AIMS: This study evaluated change in health-related quality of life (HRQOL)
      associated with ongoing weight change among patients with type 2 diabetes
      mellitus (T2DM) treated with dapagliflozin, a highly selective sodium-glucose
      cotransporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing urinary
      glucose excretion and is associated with body weight reductions. METHODS:
      Patients with T2DM who had inadequate glycaemic control on metformin (MET) alone
      were enrolled in a 24-week, double-blind, randomized, placebo-controlled study
      with a 78-week extension to evaluate the effect of dapagliflozin + MET on body
      weight. Patients also completed the Study to Help Improve Early evaluation and
      management of risk factors Leading to Diabetes Weight Questionnaire-9 (SHIELD-WQ
      9), a weight change-related HRQOL survey. Difference in proportions of patients
      treated with dapagliflozin 10 mg + MET (n = 89) or placebo + MET (n = 91) who
      reported improvement in HRQOL was analysed with Fisher's exact test. RESULTS:
      Dapagliflozin patients had significantly greater weight loss than placebo
      patients over 102 weeks (p < 0.05). This corresponded to a numerically greater
      proportion of dapagliflozin-treated patients reporting ongoing weight loss and
      associated improvements in most HRQOL domains at three different evaluation
      points (weeks 24, 50 and 102) than placebo-treated patients. In a post-hoc
      analysis among patients who reported ongoing weight loss regardless of treatment
      arm, a significantly greater proportion of patients reporting weight loss versus
      weight gain reported improvements in physical health, self-esteem and overall
      HRQOL at weeks 24, 50 and 102. CONCLUSIONS: Dapagliflozin-induced weight loss was
      associated with improvement in overall HRQOL. Overall, ongoing weight loss was
      associated with improvements in several HRQOL domains compared with weight gain.

PMID- 24443877
TI  - Low-temperature, low-pressure gas plasma application on Aspergillus brasiliensis,
      Escherichia coli and pistachios.
AB  - AIM: The aim of this study was to investigate the effect of plasma-enhanced
      chemical vapour deposition (PECVD) treatment on selected bacteria and spores and
      to contribute to the understanding of the synergistic effect of UV-directed
      plasma. METHODS AND RESULTS: The experiments were conducted on pure cultures of
      Aspergillus brasiliensis and Escherichia coli and on naturally contaminated
      pistachios that were exposed to pure oxygen-, pure argon- and to a mixture of
      oxygen-argon-generated plasma for different treatment times and at different
      micro-organism concentrations. Optical emission spectroscopy (OES) measurements
      were performed to observe the active species in the plasma. After exposure, the
      effectiveness of decontamination was assessed through microbiological techniques
      by calculating the growth reduction on a logarithmic scale. A treatment time of
      30 min resulted in a 3.5 log reduction of A. brasiliensis using pure oxygen or
      argon, while treatment times of 5 min, 1 min and 15 s resulted in a 5.4 log
      reduction using a mixture of argon and oxygen (10 : 1 v/v). Treatment times of 1
      min and 30 s resulted in a 4 log reduction of E. coli with oxygen and argon,
      respectively, which led to a complete elimination of the micro-organisms. Two-log
      reductions of fungi were achieved for pistachios after a treatment time of 1 min.
      CONCLUSIONS: These results suggest that this newly designed plasma reactor offers
      good potential applications for the reduction in micro-organisms on heat
      sensitive materials, such as foods. The plasma that was generated with Ar/O2 was
      more effective than that which was generated with pure oxygen and pure argon.
      SIGNIFICANCE AND IMPACT OF THE STUDY: An improvement in the knowledge about PECVD
      mechanisms was acquired from the chemical and biological points of view, and the
      suitability of the method for treating dry food surfaces was demonstrated.

PMID- 24443878
TI  - Extrathyroidal extension predicts extranodal extension in patients with positive
      lymph nodes: an important association that may affect clinical management.
AB  - BACKGROUND: While there is consensus that significant extrathyroidal extension
      (ETE) (T4) should upstage a patient with well-differentiated thyroid cancer, the
      importance of minimal ETE (T3) remains controversial. Additionally, the
      importance of nodal metastases on prognosis has come under scrutiny. Recent
      publications highlight the importance of size, number of positive nodes, and, in
      particular, the presence of extranodal extension (ENE) as measures of disease
      aggressiveness. In this study, we examined whether ETE is a predictor of ENE.
      METHODS: A retrospective review was conducted from January 2004 to March 2013.
      All node-positive patients who underwent total or completion thyroidectomy were
      included. Histologic features defined by the College of American Pathologists
      (CAP) protocol for thyroid carcinoma were recorded. RESULTS: A total of 193
      patients qualified for review. Patients who were found to have ETE were 12 times
      more likely to have lymph nodes in the primary setting with ENE than patients
      with intrathyroidal primary tumors (p<0.000). After exclusion of all T4 cases
      (n=6), patients with minimal ETE were 13 times more likely to have ENE than those
      with no ETE (p<0.000). Twenty percent of microcarcinomas with ETE demonstrated
      ENE. CONCLUSION: We have found that the biology of the primary tumor is conferred
      to the lymph node in that the presence of ETE leads to a significantly higher
      incidence of ENE. Awareness of this relationship should be accounted for in the
      management of primary and recurrent lymph nodes. This study shows that minimal
      ETE is a significant predictor of ENE. Although long-term survival and recurrence
      follow-up is not available for the majority of patients in this series, the
      presence of ENE as a surrogate for more aggressive disease biology and its strong
      association with minimal ETE supports the upstaging of patients with minimal ETE.

PMID- 24443879
TI  - Reproductive interference between honeybee species in artificial sympatry.
AB  - Reproductive isolation between closely related species is often incomplete. The
      Western honeybee, Apis mellifera, and the Eastern hive bee, Apis cerana, have
      been allopatric for millions of years, but are nonetheless similar in morphology
      and behaviour. During the last century, the two species were brought into contact
      anthropogenically, providing potential opportunities for interspecific matings.
      Hybrids between A. mellifera and A. cerana are inviable, so natural interspecific
      matings are of concern because they may reduce the viability of A. cerana and A.
      mellifera populations - two of the world's most important pollinators. We
      examined the mating behaviour of A. mellifera and A. cerana queens and drones
      from Caoba Basin, China and Cairns, Australia. Drone mating flight times overlap
      in both areas. Analysis of the spermathecal contents of queens with species
      specific genetic markers indicated that in Caoba Basin, 14% of A. mellifera
      queens mated with at least one A. cerana male, but we detected no A. cerana
      queens that had mated with A. mellifera males. Similarly, in Cairns, no A. cerana
      queens carried A. mellifera sperm, but one-third of A. mellifera queens had mated
      with at least one A. cerana male. No hybrid embryos were detected in eggs laid by
      interspecifically mated A. mellifera queens in either location. However, A.
      mellifera queens artificially inseminated with A. cerana sperm produced inviable
      hybrid eggs or unfertilized drones. This suggests that reproductive interference
      will impact the viability of honeybee populations wherever A. cerana and A.
      mellifera are in contact. 

PMID- 24443880
TI  - Conducting hydrogels of tetraaniline-g-poly(vinyl alcohol) in situ reinforced by
      supramolecular nanofibers.
AB  - Novel conducting hydrogels (PVA-TA) with dual network structures were synthesized
      by the grafting reaction of tetraaniline (TA) into the main chains of poly(vinyl
      alcohol) and in situ reinforced by self-assembly of a sorbitol derivative as the
      gelator. The chemical structure of the PVA-TA hydrogels was characterized by
      using FT-IR and NMR. The mechanical strength of the PVA-TA hydrogels was strongly
      improved due to the presence of supramolecular nanofibers. For instance, the
      compressive and tensile strengths of supramolecular nanofiber-reinforced
      hydrogels were, respectively, 10 times and 5 times higher than those of PVA-TA
      hydrogels. Their storage modulus (G') and loss modulus (G") were 5 times and 21
      times higher than those of PVA-TA hydrogels, respectively. Cyclic voltammetry and
      conductivity measurements indicated that the electroactivity of reinforced
      hydrogels is not influenced by the presence of supramolecular nanofibers. 

PMID- 24443881
TI  - Factors associated with successful discontinuation of hormone therapy.
AB  - BACKGROUND: Careful management of symptoms, particularly sleep and mood
      disturbances, may assist women in discontinuing hormone therapy (HT). We sought
      to describe characteristics associated with successful HT cessation in women who
      attempted to discontinue estrogen pills/patches with or without progestin.
      METHODS: We invited 2,328 women, aged 45-70, enrolled January 1, 2005, to May 31,
      2006, at Group Health in Washington State and Harvard Vanguard Medical Associates
      in Massachusetts, to participate in a telephone survey about HT practices. For
      the sample, we selected 2,090 women with estrogen dispensings (pharmacy data)
      during the study period, 200 women without HT dispensing after January 2005, and
      240 women with no estrogen dispensings; 1,358 (58.3%) completed the survey. These
      analyses are based on survey responses. RESULTS: Among 802 women who attempted HT
      discontinuation, the mean age was 50 years, 93% were postmenopausal, 90% were
      white, 30% had had a hysterectomy, and 75% experienced hot flashes after
      discontinuation. Those who did not succeed had greater trouble sleeping (74% vs.
      57%) and mood disturbances (51% vs. 34%) than those who succeeded. In
      multivariable analyses, factors associated with successful discontinuation
      included doctor advice (odds ratio [OR] 2.62, 95% confidence interval [CI] 1.68
      4.08), lack of symptom improvement (OR 4.21, CI 1.50-12.17), vaginal bleeding (OR
      5.96, CI 1.44-24.6), and learning to cope with symptoms (OR 3.36, CI 2.21-5.11).
      Factors associated with unsuccessful HT discontinuation included trouble sleeping
      (OR 0.40, CI 0.26-0.61) and mood swings or depression (OR 0.63, CI 0.42-0.92).
      CONCLUSIONS: Doctor advice is strongly associated with successful HT
      discontinuation. Symptom management, particularly sleep and mood disturbances,
      may help women discontinue HT.

PMID- 24443883
TI  - Control processes in voluntary and explicitly cued task switching.
AB  - Explicitly cued task switching slows performance relative to performing the same
      task on consecutive trials. This effect appears to be due partly to more
      efficient encoding of the task cue when the same cue is used on consecutive
      trials and partly to an additional task-switching process. These components were
      examined by comparing explicitly cued and voluntary task switching groups, with
      external cues presented to both groups. Cue-switch effects varied in predictable
      ways to dissociate explicitly cued and voluntary task switching, whereas task
      switch effects had similar characteristics for both instructional groups. The
      data were well fitted by a mathematical model of task switching that included a
      cue-encoding mechanism (whereby cue repetition improves performance) and an
      additional process that was invoked on task-switch trials. Analyses of response
      time distributions suggest that this additional process involves task-set
      reconfiguration that may or may not be engaged before the target stimulus is
      presented.

PMID- 24443882
TI  - Characterization of AcrD, a resistance-nodulation-cell division-type multidrug
      efflux pump from the fire blight pathogen Erwinia amylovora.
AB  - BACKGROUND: Multidrug efflux pumps are membrane translocases that have the
      ability to extrude a variety of structurally unrelated compounds from the cell.
      AcrD, a resistance-nodulation-cell division (RND) transporter, was shown to be
      involved in efflux of highly hydrophilic aminoglycosides and a limited number of
      amphiphilic compounds in E. coli. Here, a homologue of AcrD in the plant pathogen
      and causal agent of fire blight disease Erwinia amylovora was identified.
      RESULTS: The substrate specificity of AcrD was studied by overexpression of the
      corresponding gene from a high-copy plasmid in E. amylovora Ea1189-3, which is
      hypersensitive to many drugs due to a deficiency of the major multidrug pump
      AcrB. AcrD mediated resistance to several amphiphilic compounds including
      clotrimazole and luteolin, two compounds hitherto not described as substrates of
      AcrD in enterobacteria. However, AcrD was not able to expel aminoglycosides. An
      acrD mutant exhibited full virulence on apple rootstock and immature pear fruits.
      RT-PCR analysis revealed an induction of acrD expression in infected apple tissue
      but not on pear fruits. Moreover, a direct binding of BaeR, the response
      regulator of the two-component regulatory system BaeSR, to the acrD promoter was
      observed as has already been shown in other enterobacteria. CONCLUSIONS: AcrD
      from E. amylovora is involved in resistance to a limited number of amphiphilic
      compounds, but in contrast to AcrD of E. coli, it is not involved in resistance
      to aminoglycosides. The expression of acrD was up-regulated by addition of the
      substrates deoxycholate, naringenin, tetracycline and zinc. AcrD appears to be
      regulated by the BaeSR two-component system, an envelope stress signal
      transduction pathway.

PMID- 24443884
TI  - Anti-influenza A virus activity of a new dihydrochalcone diglycoside isolated
      from the Egyptian seagrass Thalassodendron ciliatum (Forsk.) den Hartog.
AB  - One new dihydrochalcone diglycoside has been isolated from the EtOAc fraction of
      the Egyptian seagrass Thalassodendrin ciliatum (Forsk.) den Hartog, and was
      identified as 6'-O-rhamnosyl-(1''' -> 6")-glucopyranosyl asebogenin for which a
      trivial name Thalassodendrone was established. Furthermore, five known phenolics
      were isolated and identified as asebotin, quercetin 3,7-diglucoside,
      protocatechuic acid, ferulic acid and p-hydroxybenzoic acid. The structures of
      all the isolated compounds were established based on 1D and 2D NMR spectroscopy
      and high-resolution-mass spectrometer. High-resolution electrospray ionization
      mass spectra (HR-ESI-MS) were obtained using a JEOL JMS-T100TD spectrometer (JEOL
      Ltd., Tokyo, Japan). The anti-influenza A virus activity of the isolated new
      compound and asebotin was evaluated, and the obtained results revealed that the
      inhibition dose concentration of asebotin was more than that of Thalassodendrone
      with IC50 = 2.00 and 1.96 MUg/mL, respectively, and with cytotoxic concentration
      (CC50) of 3.36 and 3.14 MUg/mL, respectively.

PMID- 24443887
TI  - The modified Hospital Elder Life Program: adapting a complex intervention for
      feasibility and scalability in a surgical setting.
AB  - The purpose of this article is to provide the rationale and methods for adapting
      the Hospital Elder Life Program (HELP). The HELP is a complex intervention that
      has been shown to reduce rates of delirium and functional decline. However,
      modification of the program may be required to meet local circumstances and
      specialized populations. We selected three key elements based on our prior work
      and the concept of shared risk factors and modified the HELP to include only
      three shared risk factors (functional, nutritional, and cognitive status) that
      were targeted by three nursing protocols: early mobilization, oral and
      nutritional assistance, and orienting communication. These protocols were
      adapted, refined, and pilot-tested for feasibility and efficacy. We hope by
      reporting the rationale and protocols for the modified HELP, we will advance the
      field for others adapting evidence-based, complex nursing interventions.

PMID- 24443886
TI  - Cryptic adaptive radiation in tropical forest trees in New Caledonia.
AB  - The causes of the species richness of tropical trees are poorly understood, in
      particular the roles of ecological factors such as soil composition. The
      nickel(Ni)-hyperaccumulating tree genus Geissois (Cunoniaceae) from the South
      west Pacific was chosen as a model of diversification on different substrates.
      Here, we investigated the leaf element compositions, spatial distributions and
      phylogeny of all species of Geissois occurring on New Caledonia. We found that
      New Caledonian Geissois descended from a single colonist and diversified
      relatively quickly into 13 species. Species on ultramafic and nonultramafic
      substrates showed contrasting patterns of leaf element composition and range
      overlap. Those on nonultramafic substrates were largely sympatric but had
      distinct leaf element compositions. By contrast, species on ultramafic substrates
      showed similar leaf element composition, but occurred in many cases exclusively
      in allopatry. Further, earlier work showed that at least three out of these seven
      species use different molecules to bind Ni. Geissois qualifies as a cryptic
      adaptive radiation, and may be the first such example in a lineage of tropical
      forest trees. Variation in biochemical strategies for coping with both typical
      and adverse soil conditions may help to explain the diversification and
      coexistence of tropical forest trees on similar soil types. 

PMID- 24443885
TI  - Evidence to support natural hybridization between Anopheles sinensis and
      Anopheles kleini (Diptera: Culicidae): possibly a significant mechanism for gene
      introgression in sympatric populations.
AB  - BACKGROUND: Malaria caused by Plasmodium vivax is still a public health problem
      in the Republic of Korea (ROK), particularly regarding the recent re-emergence of
      this malarial species near the demilitarized zone in northwestern Paju City,
      Gyeonggi-do Province. Currently, at least 4 species (An. kleini, An. pullus, An.
      belenrae and An. lesteri) of the Hyrcanus Group are reported as possible natural
      vectors of vivax malaria in the ROK, and An. sinensis, which is the most dominant
      species, has long been incriminated as an important natural vector of this P.
      vivax. However, An. sinensis was ranked recently as a low potential vector.
      According to the discovery of natural hybrids between An. sinensis (a low
      potential vector for P. vivax) and An. kleini (a high potential vector for P.
      vivax) in Paju City, intensive investigation of this phenomenon is warranted
      under laboratory conditions. METHODS: Mosquitoes were collected during 2010-2012
      from Paju City, ROK. Hybridization experiments used iso-female line colonies of
      these anophelines together with DNA analysis of ribosomal DNA [second internal
      transcribed spacer (ITS2)] and mitochondrial DNA [cytochrome c oxidase subunit I
      (COI)] of the parental colonies, F1-hybrids and repeated backcross progenies were
      performed intensively by using a PCR-based assay and pyrosequencing technology.
      RESULTS: The results from hybridization experiments and molecular investigations
      revealed that the mitochondrial COI gene was introgressed from An. sinensis into
      An. kleini. The An. sinensis progenies obtained from consecutive repeated
      backcrosses in both directions, i.e., F2-11 progeny [(An. sinensis x An. kleini)
      x An. sinensis] and F3-5 progeny [(An. kleini x An. sinensis) x An. kleini]
      provided good supportive evidence. CONCLUSIONS: This study revealed introgression
      of the mitochondrial COI gene between An. sinensis and An. kleini through
      consecutive repeated backcrosses under laboratory conditions. This new body of
      knowledge will be emphasized in reliable promising strategies in order to replace
      the population of An. kleini as a high potential vector for P. vivax, with that
      of a low potential vector, An. sinensis, through the mechanism of gene
      introgression in nature.

PMID- 24443888
TI  - Using a book chat to improve attitudes and perceptions of long-term care staff
      about dementia.
AB  - This study sought to evaluate a book chat intervention based on Lisa Genova's
      novel, Still Alice, to influence long-term care (LTC) staff perceptions and
      attitudes when caring for individuals with dementia. A qualitative descriptive
      design was used. Eleven participants partook in a 2.5-hour book chat at a
      southern Ontario LTC facility. Following the book chat, participants answered two
      open-ended questions to assess how the book chat influenced their views on
      dementia. Thematic content analysis was used to analyze the qualitative
      questionnaire. Content analysis of the participants' responses revealed that the
      book chat positively influenced their attitudes and perceptions toward dementia,
      particularly by providing more insight into the individual's personal struggle
      with the disease. Furthermore, participants found that the book chat influenced
      their care practices. By creating innovative learning opportunities, attitudes
      and perceptions about dementia care can be transcended and greatly benefit staff,
      family, and residents.

PMID- 24443889
TI  - Numerical comparison of iodine-based and indium-based antibody biodistributions.
AB  - PURPOSE: Single-step iodination is often performed in preference to use of a
      radiometal label for initial animal biodistributions. Yet loss of iodine occurs
      in vivo so that it is important to measure uptake (%ID/g) differences between
      radiolabels. METHODS: Murine biodistributions of four radioiodinated and (111)In
      labeled cognate anti-carcinoembryonic antigen antibodies were compared. Uptakes
      were obtained in athymic mice out to 96 hours for diabody, minibody, scFv-Fc, and
      intact humanized (M5A) versions of the T84.66 antibody. Tissues included liver,
      spleen, kidneys, lungs, and human LS174T colorectal xenografts. Ratios (R) of
      iodine uptake to indium uptake were calculated. RESULTS: For all cognates, no
      significant differences were found in the blood uptakes between the two labels.
      In normal solid organs, iodine was generally cleared more rapidly with decreasing
      molecular weight (MW). In liver and spleen by 24 hours, the R value was 5% for
      diabody and minibody, whereas a value of 50% was seen for the intact mAb. Renal
      differences were even more marked for the two lower MW species. Tumor losses,
      however, were found to be essentially independent of MW and were modest; 50% by
      48 hours. To test the generality of the results, comparisons were then made for
      normal organs and tumors of the R values found above for M5A and MN-14 intact
      antibody literature results. Good agreement, within estimated errors in R, was
      seen between these two cases, although (111)In and (88)Y were the respective
      radiometals. CONCLUSIONS: Loss of iodine from labeled antibodies can be marked in
      normal organs and that correction (by 1/R) of the iodine biodistribution to
      estimate the associated radiometal result may be possible. Explicit differences
      between the two types of biodistribution also imply that separate uptake results
      need to be considered when evaluating the impact on imaging and therapy using
      various possible radiolabels.

PMID- 24443890
TI  - Design and assembly of pH-sensitive lipidic cubic phase matrices for drug
      release.
AB  - Bicontinuous lipidic cubic phases (LCPs) exhibit a combination of material
      properties that make them highly interesting for various biomaterial
      applications: they are nontoxic, biodegradable, optically transparent,
      thermodynamically stable in excess water, and can incorporate active molecules of
      virtually any polarity. Here we present a molecular system comprising host lipid,
      water, and designed lipidic additive, which form a structured, pH-sensitive
      lipidic matrix for hydrophilic as well as hydrophobic drug incorporation and
      release. The model drug doxorubicin (Dox) was loaded into the LCP. Tunable
      interactions with the lipidic matrix led to the observed pH-dependent drug
      release from the phase. The rate of Dox release from the cubic phase at pH 7.4
      was low but increased significantly at more acidic pH. A small amount of a
      tailored diacidic lipid (lipid 1) added to the monoolein LCP modified the release
      rate of the drug. Phase identity and structural parameters of pure and doped
      mesophases were characterized by small-angle X-ray scattering (SAXS), and release
      profiles from the matrix were monitored electrochemically. Analysis of the
      release kinetics revealed that the total amount of drug released from the LCP
      matrix is linearly dependent on the square root of time, implying that the
      release mechanism proceeds according to the Higuchi model. 

PMID- 24443892
TI  - Desmoid tumor-associated pain is dependent on mast cell expression of
      cyclooxygenase-2.
AB  - BACKGROUND: This study aimed to investigate the expression profile of
      cyclooxygenase-2 (COX-2) in desmoid tumor specimens and to evaluate the
      correlation of intratumoral COX-2 expression with pain status. METHODS: Sixteen
      patients with histologically proven desmoid tumors who attended our institution
      between 2003 and 2010 were enrolled in this study. COX-2 protein expression in
      desmoid tumors was determined by immunohistochemistry. COX-2 - positive cells had
      similar morphology to that of mast cells, and therefore, immunohistochemical
      staining for tryptase was performed in co-localized sections. The number of COX-2
      -positive cells in 10 consecutive fields was counted at 400* magnification.
      Patients were stratified into 2 groups according to the number of COX-2- positive
      cells, the COX-2 -positive group (?10 COX-2 -positive cells) and the COX-2 
      negative group (<10 COX-2 -positive cells). The prevalence of painful tumors was
      compared between the 2 groups. RESULTS: COX-2 was expressed in 9 patients (56%).
      COX-2 proteins were expressed not in tumor cells but in tryptase-positive mast
      cells in the stroma of desmoid tumors. 6 of 9 patients in COX-2 -positive group
      had painful tumors. This difference was statistically significant according to
      the chi-squared test (p = 0 .036), suggesting a positive correlation between COX
      2 expression and tumor-associated pain. CONCLUSIONS: Our results indicated that
      COX-2 secretion from mast cells modulates desmoid tumor-associated pain. In
      addition, mast cells may at least in part contribute to the pathogenesis of
      desmoid tumors. VIRTUAL SLIDE: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/1490389349103056.

PMID- 24443891
TI  - New diagnostic strategy for sepsis-induced disseminated intravascular
      coagulation: a prospective single-center observational study.
AB  - INTRODUCTION: Inflammation and coagulation are closely interrelated
      pathophysiologic processes in the pathogenesis of sepsis. However, the diagnostic
      criteria of sepsis and disseminated intravascular coagulation (DIC) are
      different. This study aimed to define a biomarker panel to predict sepsis-induced
      DIC in emergency department patients. METHODS: Eighty-two patients who were
      admitted to the emergency department of a tertiary university hospital were
      included in this study. The inclusion criteria were as follows: (1) age >18
      years; (2) >=1 systemic inflammatory response syndrome (SIRS) criteria. Patients
      were excluded if they lacked biomarker data or apparent clinical manifestations.
      Eleven biomarkers were assayed from blood drawn on ED admission. Receiver
      operating curve (ROC) analysis including the area under the ROC and multivariable
      logistic regression were used to identify an optimal combination of biomarkers to
      create a diagnostic panel. The derived formula for weighting biomarker values was
      used to determine the severity of sepsis-induced DIC, which was divided into
      three categories: mild, moderate, and severe. We also investigated the ability of
      this classification to predict secondary outcome measures of rates of sepsis and
      DIC, DIC score, acute physiology and chronic health evaluation (APACHE) II score,
      sequential organ failure score (SOFA) score, and 28-day all-cause mortality.
      RESULTS: Among the 11 biomarkers tested, the optimal 2-marker panel comprised
      presepsin and protein C. The area under the curve for the accuracies of
      predicting sepsis and DIC from these two biomarkers were 0.913 and 0.880,
      respectively. When patients were divided according to the severity of sepsis
      induced DIC, all secondary outcomes except for mortality were significantly
      higher depending on the severity (P < .0001). The overall mortality rates of
      mild, moderate, and severe sepsis-induced DIC were 7.14%, 15.4%, and 28.6%,
      respectively (P = .0994). CONCLUSIONS: A biomarker panel of presepsin and protein
      C is predictive of the severity of sepsis-induced DIC in suspected ED patients.
      These criteria for sepsis-induced DIC are very simple, easy to implement, and can
      be used in intensive care units as a point-of-care test.

PMID- 24443893
TI  - Development and validation of a reversed-phase high-performance liquid
      chromatography method for routine identification and purity assessment of high
      purity steviol glycoside sweeteners.
AB  - The widespread application of stevia-based sweeteners in food products has
      resulted in the need for reliable analytical methods for measuring the purity and
      identity of high-purity steviol glycoside ingredients. The objective of this
      research was to develop and validate a new reversed-phase separation method
      capable of separating and quantifying nine steviol glycosides present in typical
      high-purity stevia extract ingredients. Results of the study established the
      linearity of the method at a correlation factor of 1.000 for the two major
      components and other minor components of this food ingredient. Method accuracy
      values were in the range of 99.1-100.9%. The percent relative standard deviation
      for six independent assay determinations was 1.0%. The method was determined to
      be robust for minor changes in column temperature, initial acetonitrile content,
      flow rate, and wavelength. The validated high-performance liquid chromatography
      method was found to be suitable to be included by USP as a Food Chemicals Codex
      compendial standard for steviol glycosides. 

PMID- 24443894
TI  - IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid
      leukemia lacking the NPM1 mutation.
AB  - We examined the incidence and prognostic effect of IDH1 and IDH2 mutations in 233
      Japanese adults with acute myeloid leukemia (AML). IDH1 R132 mutations were
      detected in 20 (8.6%) patients with AML. IDH2 mutations were found in 19 (8.2%,
      17 R140 and two R172) patients. IDH1 and IDH2 mutations were mutually exclusive
      and were associated with normal karyotype AML, cytogenetic intermediate-risk
      group, and NPM1 mutations. Five-year overall survival (OS) rates were
      significantly lower (15.6%) in patients harboring the IDH mutations than in
      patients lacking the IDH mutation (32.0%) in the entire cohort of AML (P =
      0.005). Among patients aged 59 yr or younger with IDH mutations, 5-yr OS in
      patients who underwent allogeneic stem cell transplantation (SCT) was
      significantly higher than that in those not receiving allogeneic SCT (50% vs.
      10.6%, P = 0.020). Of 51 patients with NPM1 mutations, there was no significant
      difference in 5-yr OS rates between patients with and those without the IDH
      mutations. In contrast, among 175 patients lacking the NPM1 mutations, 5-yr OS
      rate in patients with IDH mutations was significantly lower than that in those
      without IDH mutations (0% vs. 34.7%, P = <0.001). These data suggest that IDH
      mutations have an unfavorable effect in AML, especially AML with the NPM1 wild
      type and younger AML patients with IDH mutations may benefit from allogeneic SCT.

PMID- 24443895
TI  - Molecular phylogeny and symbiotic selectivity of the green algal genus
      Dictyochloropsis s.l. (Trebouxiophyceae): a polyphyletic and widespread group
      forming photobiont-mediated guilds in the lichen family Lobariaceae.
AB  - Dictyochloropsis s.l. is an ecologically important, common but little-studied
      genus of green algae. Here, we examined the diversity and host selectivity of
      algae attributed to this genus at both species-to-species and species-to
      community levels. We conducted a molecular investigation of 15 cultured strains
      and several lichen photobionts, using 18S rRNA, rbcL and ITS sequence data. We
      further used seven alga-specific microsatellite markers to study algal sharing
      among fungi of the family Lobariaceae in two populations in Madeira and Taiwan
      (454 lichens). We found that the genus Dictyochloropsis s.l. is polyphyletic.
      Dictyochloropsis clade 1 comprises only free-living algae whereas
      Dictyochloropsis clade 2 includes lichenized algae as well as free-living algae.
      Fungal selectivity towards algae belonging to Dictyochloropsis clade 2 is high.
      Selectivity varies geographically, with photobionts being restricted to a single
      region. Finally, we showed that Dictyochloropsis clade 2 individuals are shared
      among different fungal hosts in communities of lichens of the Lobariaceae. As for
      other green algal lineages, there is a high amount of cryptic diversity in
      Dictyochloropsis. Furthermore, co-evolution between Dictyochloropsis clade 2
      algae and representatives of the Lobariaceae is manifested at the community
      level, with several unrelated fungal species being horizontally connected by
      shared photobiont clones. 

PMID- 24443896
TI  - Ultralong, small-diameter TiOTiO2 nanotubes achieved by an optimized two-step
      anodization for efficient dye-sensitized solar cells.
AB  - An optimized two-step anodization is developed to fabricate ultralong, small
      diameter TiO2 nanotubes, that is, with tube length of up to 31 MUm and pore
      diameter of about 35 nm in this work. This overcomes the length limitation of
      small diameter tubes that usually presents in conventional one-step anodization.
      The small tubes with lengths of 23 MUm yield a conversion efficiency of 5.02% in
      dye-sensitized solar cells under nonoptimized conditions. 

PMID- 24443897
TI  - New TMD classification - new year for JOR.

PMID- 24443899
TI  - Prevalence of whiplash trauma in TMD patients: a systematic review.
AB  - The purpose of this systematic review was to describe the prevalence of whiplash
      trauma in patients with temporomandibular disorders (TMDs) and to describe
      clinical signs and symptoms in comorbid TMD/whiplash compared with TMD localised
      to the facial region. A systematic literature search of the PubMed, Cochrane
      Library and Bandolier databases was carried out for articles published from 1
      January 1966 to 31 December 2012. The systematic search identified 129 articles.
      After the initial screening of abstracts, 32 articles were reviewed in full text
      applying inclusion and exclusion criteria. Six studies on the prevalence of neck
      trauma in patients with TMD met the inclusion criteria and were included in the
      review. Two of the authors evaluated the methodological quality of the included
      studies. The reported prevalence of whiplash trauma ranged from 8.4% to 70%
      (median 35%) in TMD populations, compared with 1.7-13% in the non-TMD control
      groups. Compared with patients with TMD localised to the facial region, TMD
      patients with a history of whiplash trauma reported more TMD symptoms, such as
      limited jaw opening and more TMD pain, and also more headaches and stress
      symptoms. In conclusion, the prevalence of whiplash trauma is higher in patients
      with TMD compared with non-TMD controls. Furthermore, patients with comorbid
      TMD/whiplash present with more jaw pain and more severe jaw dysfunction compared
      with TMD patients without a history of head-neck trauma. These results suggest
      that whiplash trauma might be an initiating and/or aggravating factor as well as
      a comorbid condition for TMD. 

PMID- 24443898
TI  - Expanding the taxonomy of the diagnostic criteria for temporomandibular
      disorders.
AB  - There is a need to expand the current temporomandibular disorders' (TMDs)
      classification to include less common but clinically important disorders. The
      immediate aim was to develop a consensus-based classification system and
      associated diagnostic criteria that have clinical and research utility for less
      common TMDs. The long-term aim was to establish a foundation, vis-a-vis this
      classification system, that will stimulate data collection, validity testing and
      further criteria refinement. A working group [members of the International
      RDC/TMD Consortium Network of the International Association for Dental Research
      (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the
      International Association for the Study of Pain (IASP), and members from other
      professional societies] reviewed disorders for inclusion based on clinical
      significance, the availability of plausible diagnostic criteria and the ability
      to operationalise and study the criteria. The disorders were derived from the
      literature when possible and based on expert opinion as necessary. The expanded
      TMDs taxonomy was presented for feedback at international meetings. Of 56
      disorders considered, 37 were included in the expanded taxonomy and were placed
      into the following four categories: temporomandibular joint disorders,
      masticatory muscle disorders, headache disorders and disorders affecting
      associated structures. Those excluded were extremely uncommon, lacking
      operationalised diagnostic criteria, not clearly related to TMDs, or not
      sufficiently distinct from disorders already included within the taxonomy. The
      expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and
      provides a framework for further research to operationalise and test the proposed
      taxonomy and diagnostic criteria.

PMID- 24443900
TI  - Economic burden of seasonal influenza B in France during winter 2010-2011.
AB  - BACKGROUND: In France, 2-15% of the population is affected annually by influenza,
      which causes significant socioeconomic disruption. Nevertheless, despite its
      importance for policy makers, few published studies have evaluated the impact of
      influenza B. Therefore, we assessed the costs associated with influenza B during
      2010-2011 in France. METHODS: Cases of lab-confirmed influenza B were analyzed as
      part of the Influenza B in General Practice Study. Cost calculations were based
      on micro-costing methods according to the French Health Insurance (FHI)
      perspective (in Euros, 2011). Costs were compared between age groups using the
      Kruskal-Wallis test, and when significant, by multiple comparisons based on rank.
      Moreover, uncertainties were assessed using one-way sensitivity and probabilistic
      analyses. Overall economic burden was estimated by multiplying cost per patient,
      flu attack rate, and the French population. RESULTS: A total of 201 patients were
      included in the study. We found that the mean cost associated with Influenza B
      was 72? (SD: 205) per patient: 70? (SD: 262) for younger children, 50? (SD: 195)
      for older children, 126? (SD: 180) for adults, and 42? (SD: 18) for elderly.
      Thus, we observed significantly different costs between the distinct age groups
      (p<0.0001). Finally, the economic burden of influenza B for the FHI was estimated
      to be 145 million Euros (95% CI: 88-201). CONCLUSIONS: Our findings highlight the
      important impact of influenza B and encourage further investigation on policy
      regarding vaccination strategies in France.

PMID- 24443901
TI  - Active commuting to elementary school and adiposity: an observational study.
AB  - BACKGROUND: Active commuting to school (ACS; walking or cycling to school)
      appears promising for decreasing children's obesity risk, although long-term
      studies are sparse. The aim was to examine whether kindergarten ACS was
      associated with fifth-grade adiposity. METHODS: This study was a secondary
      analysis of the Early Childhood Longitudinal Study, Kindergarten (n=7938).
      Enrollment in kindergarten (1998-1999) was nationally representative of the
      United States and follow-up occurred in 2004. Kindergarten ACS was the main
      exposure variable and fifth-grade BMI z-score was the main outcome measure.
      Covariates included (1) neighborhood safety and BMI z-score in kindergarten and
      (2) demographics (i.e., age, gender, race/ethnicity, socioeconomic status, single
      vs. two-parent households, region of country, and urbanicity in fifth grade).
      Three interactions were included: school travel*neighborhood safety; school
      travel*BMI z-score (kindergarten); and school travel*socioeconomic status.
      Analysis of covariance accounted for the complex sampling design. RESULTS:
      Kindergarten ACS was associated with lower BMI z-score in fifth grade. The
      interaction of school travel*neighborhood safety indicated that children from
      less-safe neighborhoods who did ACS in kindergarten had a lower fifth-grade BMI z
      score (p<0.05) than their peers who did not do ACS in kindergarten (i.e., in
      terms of BMI, this difference was -0.49 kg/m(2) for children of average height in
      less-safe neighborhoods). CONCLUSION: Among children from less-safe
      neighborhoods, kindergarten ACS independently predicted lower BMI z-score in
      fifth grade among a national US cohort. Interventions and policies to increase
      ACS among young children, especially from unsafe neighborhoods, are warranted and
      should address parents' safety concerns.

PMID- 24443902
TI  - A touch of glue to complete bacteriophage assembly: the tail-to-head joining
      protein (THJP) family.
AB  - Bacteriophage SPP1 is a nanomachine built to infect the bacterium Bacillus
      subtilis. The phage particle is composed of an icosahedric capsid, which contains
      the viral DNA, and a long non-contractile tail. Capsids and tails are produced in
      infected cells by two distinct morphogenetic pathways. Characterization of the
      suppressor-sensitive mutant SPP1sus82 showed that it produces DNA-filled capsids
      and tails but is unable to assemble complete virions. Its purified tails have a
      normal length but lack a narrow ring that tapers the tail end found at the tail
      to-head interface. The mutant is defective in production of gp17. The gp17 ring
      is exposed in free tails competent for viral assembly but becomes shielded in the
      final virion structure. Recombinant gp17 is active in an in vitro assay to stick
      together capsids and tails present in extracts of SPP1sus82-infected cells,
      leading to formation of infectious particles. Gp17 thus plays a fundamental role
      in the tail-to-head joining reaction, the ultimate step of virus particle
      assembly. This is the conserved function of gp17 and its structurally related
      proteins like lambda gpU. This family of proteins can also provide fidelity to
      termination of the tail tube elongation reaction in a subset of phages including
      coliphage lambda. 

PMID- 24443904
TI  - A new prenylated indole derivative from endophytic actinobacteria Streptomyces
      sp. neau-D50.
AB  - A new prenylated indole derivative 3-acetonylidene-7-prenylindolin-2-one (1) was
      isolated from the endophytic actinobacterium Streptomyces sp. neau-D50, together
      with four known hybrid isoprenoids, 7-isoprenylindole-3-carboxylic acid (2), 3
      cyanomethyl-6-prenylindole (3), 6-isoprenylindole-3-carboxylic acid (4) and 7,4'
      dihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (5). The structures
      of these compounds were elucidated on the basis of extensive spectroscopic
      analysis and comparison with data from the literature. Compounds 1 and 2
      demonstrated strong cytotoxic activities against human lung adenocarcinoma cell
      line A549 with an IC50 of 3.3 and 5.1 MUg mL(- 1), respectively, which are
      comparable to that of the positive control doxorubicin (4.2 MUg mL(- 1)).
      Furthermore, compounds 1-4 exhibited potent antifungal activity against
      phytopathogenic fungi Colletotrichum orbiculare, Phytophthora capsici,
      Corynespora cassiicola and Fusarium oxysporum. 

PMID- 24443906
TI  - Nurse health-related quality of life: associations with patient and ward
      characteristics in Japanese general acute care wards.
AB  - AIM: To investigate the factors affecting nurse health-related quality of life
      (HRQOL) by considering the patient characteristics and ward characteristics.
      BACKGROUND: Nurse health-related quality of life is an important health outcome,
      and should be promoted for quality nursing care. METHOD: This cross-sectional
      study was conducted on nurses who work in general acute care wards in three
      university hospitals in metropolitan Japan. Multilevel analysis was conducted to
      investigate possible factors related to nurse health-related quality of life.
      RESULT: Nurses who worked at a ward had a significantly lower physical health
      score (beta = -0.13, P < 0.01). These nurses had a higher ratio of patients who
      could not understand medical instructions, had cognitive disabilities, or
      required assistance with activities of daily living (ADL). The number of beds was
      the only factor significantly related to mental health status of nurses (beta =
      0.19, P < 0.05). CONCLUSION: Work conditions that sustain nurse health should
      take into account not only the number of nurses, but also patient
      characteristics. Further large-scale studies are needed in order to investigate
      the effect of hospital characteristics on nurse health-related quality of life.
      IMPLICATIONS FOR NURSING MANAGEMENT: Increasing the number of nurses' aides and
      delegating assistance with ADL to them could support nurse health-related quality
      of life in the acute care setting.

PMID- 24443907
TI  - Plain language summaries in the British Journal of Dermatology: connecting with
      patients.

PMID- 24443905
TI  - Extracorporeal membrane oxygenation in adult patients with hematologic
      malignancies and severe acute respiratory failure.
AB  - INTRODUCTION: Acute respiratory failure (ARF) is the main reason for intensive
      care unit (ICU) admissions in patients with hematologic malignancies (HMs). We
      report the first series of adult patients with ARF and HMs treated with
      extracorporeal membrane oxygenation (ECMO). METHODS: This is a retrospective
      cohort study of 14 patients with HMs (aggressive non-Hodgkin lymphoma (NHL) n =
      5; highly aggressive NHL, that is acute lymphoblastic leukemia or Burkitt
      lymphoma, n = 5; Hodgkin lymphoma, n = 2; acute myeloid leukemia, n = 1; multiple
      myeloma, n = 1) receiving ECMO support because of ARF (all data as medians and
      interquartile ranges; age, 32 years (22 to 51 years); simplified acute physiology
      score II (SAPS II): 51 (42 to 65)). Etiology of ARF was pneumonia (n = 10),
      thoracic manifestation of NHL (n = 2), sepsis of nonpulmonary origin (n = 1), and
      transfusion-related acute lung injury (n = 1). Diagnosis of HM was established
      during ECMO in four patients, and five first received (immuno-) chemotherapy on
      ECMO. RESULTS: Before ECMO, the PaO2/FiO2 ratio was 60 (53 to 65), (3.3 to 3.7).
      Three patients received venoarterial ECMO because of acute circulatory failure in
      addition to ARF; all other patients received venovenous ECMO. All patients needed
      vasopressors, and five needed hemofiltration. Thrombocytopenia occurred in all
      patients (lowest platelet count was 20 (11 to 21) G/L). Five major bleeding
      events were noted. ECMO duration was 8.5 (4 to 16) days. ICU and hospital
      survival was 50%. All survivors were alive at follow-up (36 (10 to 58) months);
      five patients were in complete remission, one in partial remission, and one had
      relapsed. CONCLUSIONS: ECMO therapy is feasible in selected patients with HMs and
      ARF and can be associated with long-term disease-free survival.

PMID- 24443908
TI  - Quality of life in dermatology: after 125 years, time for more rigorous
      reporting.

PMID- 24443909
TI  - Heterogeneity of psoriasis and bimodal activation of local immune responses.

PMID- 24443910
TI  - Skin cancer: more than skin deep?

PMID- 24443911
TI  - Opening the melanoma black box.

PMID- 24443912
TI  - Major therapeutic developments and current challenges in advanced melanoma.
AB  - Malignant melanoma is rising in incidence. The treatment options have been very
      limited but advances in molecular biology and immunology have led to a greater
      understanding of the pathogenesis of the disease. Four drugs have been approved
      for the treatment of advanced melanoma in the past 2 years and two new classes of
      agents have recently been shown to lead to durable responses in a substantial
      minority of patients. The identification of biomarkers has helped clinicians and
      researchers segregate patients into molecular subgroups, which facilitates the
      selection of therapy. Preliminary work has begun on determining the ideal
      sequences of the various therapies. Investigations have been carried out on why
      these treatments work and what the mechanisms of resistance are to these
      therapies. It is hoped that combinations of therapies will emerge that lead to a
      high percentage of durable responses.

PMID- 24443913
TI  - Risk of second primary malignancies following a diagnosis of cutaneous malignant
      melanoma or nonmelanoma skin cancer in Alberta, Canada from 1979 to 2009.
AB  - BACKGROUND: Recent studies have revealed geographical variations with respect to
      the risk of second primary malignancies (SPMs) following cutaneous malignant
      melanoma (CMM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To provide the
      largest analysis of the risk of SPM following skin cancers in Canada and to
      detect associations that may shed light on common pathogeneses between linked
      malignancies. METHODS: Relative risks for development of SPMs following a
      diagnosis of CMM or NMSC were calculated via a retrospective analysis of data
      retrieved from the Alberta Cancer Registry (ACR) from 1979 to 2009. RESULTS: From
      1979 to 2009, 85,967 NMSC and 6884 CMM incident cases were recorded in the ACR.
      In total 19,869 SPMs were identified following a primary NMSC (7709 cutaneous and
      12,160 noncutaneous), while 1437 SPMs (908 cutaneous and 529 noncutaneous)
      followed CMM. Patients with a previous history of skin cancer had a 60% increased
      risk of developing an SPM compared with those without [observed/expected ratio
      (O/E) 1.6, 95% confidence interval (CI) 1.6-1.7; P < 0.001]. Thirty and 10
      different SPMs were significantly identified to follow a diagnosis of NMSC and
      CMM, respectively. Patients under the age of 40 years with a prior history of CMM
      had a marked increased expectancy for SPM [O/E 5.6, 95% CI 4.5-7.0; P < 0.001).
      CONCLUSIONS: Further studies are warranted to identify environmental and
      molecular connections among linked cutaneous and noncutaneous malignancies, which
      may lead to earlier detection of related neoplasms via expanded screening
      protocols and development of shared treatment regimens. Heightened surveillance
      for the development of SPMs in patients with CMM under the age of 40 years should
      be considered.

PMID- 24443914
TI  - Indicators for the total number of melanocytic naevi: an adjunct for screening
      campaigns. Observational study on 292 patients.
AB  - BACKGROUND: The presence of multiple melanocytic naevi is a strong risk factor
      for melanoma. Use of the whole body naevus count to identify at-risk patients is
      impractical. OBJECTIVES: To (i) identify a valid anatomical predictor of total
      naevus count; (ii) determine the number of naevi that most accurately predict
      total naevus count above 25, 50 and 100; and (iii) evaluate determinants of
      multiple melanocytic naevi and atypical naevi. METHODS: Clinical data from 292
      consecutive Spanish patients consulting for skin lesions requiring debriding were
      collected throughout 2009 and 2010. Correlations between site-specific and whole
      body naevus counts were analysed. Cut-offs to predict total naevus counts were
      determined using the area under the receiver operating characteristic curve.
      RESULTS: The studied population was young (median age 31 years, interquartile
      range 28-43). The naevus count on the right arm correlated best with the total
      nevus count (R(2) 0.80 for men, 0.86 for women). Presence of at least five naevi
      on the right arm was the strongest determinant of a total naevus count above 50
      [odds ratio (OR) 34.4, 95% confidence interval (CI) 13.9-85.0] and of having at
      least one atypical naevus (OR 5.7, 95% CI 2.4-13.5). Cut-off values of 6, 8 and
      11 naevi on the right arm best predicted total naevus count above 25, 50 and 100,
      respectively. CONCLUSIONS: Our results support the arm as a practical and
      reliable site to estimate the total naevus count when screening or phenotyping
      large populations. Threshold values for the number of naevi on the arm are
      proposed to help identify patients for melanoma screening.

PMID- 24443915
TI  - Mutations in EXPH5 result in autosomal recessive inherited skin fragility.
AB  - Several different genes have been implicated in the pathophysiology of inherited
      blistering skin diseases. Recently, autosomal recessive loss-of-function
      mutations in EXPH5 (encoding exophilin-5, also known as Slac2-b, a protein
      involved in intracellular vesicle transport) were identified in a new
      mechanobullous disease resembling a form of epidermolysis bullosa simplex (EBS).
      Here, we searched for mutations in EXPH5 in a 4-year-old white boy with EBS in
      whom initial Sanger sequencing of known genes implicated in intraepidermal skin
      fragility failed to identify pathogenic mutations. Transmission electron
      microscopy of rubbed nonlesional patient skin revealed disruption of
      keratinocytes in the lower epidermis with cytolysis and acantholysis, keratin
      filament clumping and prominent perinuclear cytoplasmic vesicles, and provided
      the clue to the candidate gene pathology. Sanger sequencing of genomic DNA showed
      compound heterozygosity for two new mutations in EXPH5, c.1947dupC
      (p.Pro649fsPro*11) and c.2249C>A (p.Ser750*). Immunofluorescence microscopy of
      patient skin showed a complete absence of exophilin-5 labelling. This case
      represents the third pedigree with EXPH5 mutations resulting in inherited skin
      fragility. The clinical and molecular data expand genotype-phenotype correlation
      in this new form of EBS and demonstrate the important role of exophilin-5 in
      keratinocyte cell biology. 

PMID- 24443919
TI  - Layer-by-layer synthesis of mechanically robust solvent-permeable silica
      nanoshells.
AB  - A layer-by-layer (LbL) synthesis of mechanically robust micrometer-diameter
      nanoshell silica was developed. Silica was templated onto polstyrene latex
      particles using a modified Stober synthesis. Each subsequent silica layer was
      deposited after adsorbing cationic polymer poly(allylamine) hydrochloride. The
      silica shell grew approximately 30 nm for each reaction step. The polystyrene
      silica core-shell particles were calcined at 500  degrees C to remove the latex
      core. The synthesis was adapted to nonspherical shapes using anisotropic
      polystyrene dicolloids as templates. The silica nanoshells were functionalized to
      render them organophilic or fluorescent. The rates at which water, ethanol, and
      aqueous sucrose solution (60% w/w) permeate the silica shells were compared using
      spectrophotometry and conductivity measurements. The rate of solvent uptake
      ranged between under 1 h to over 1 week depending on the surface chemistry of the
      nanoshells. 

PMID- 24443920
TI  - A socially situated approach to inform ways to improve health and wellbeing.
AB  - Mainstream health psychology supports neoliberal notions of health promotion in
      which self-management is central. The emphasis is on models that explain
      behaviour as individually driven and cognitively motivated, with health beliefs
      framed as the favoured mechanisms to target in order to bring about change to
      improve health. Utilising understandings exemplified in critical health
      psychology, we take a more socially situated approach, focusing on practicing
      health, the rhetoric of modernisation in UK health care and moves toward
      democratisation. While recognising that within these new ways of working there
      are opportunities for empowerment and user-led health care, there are other
      implications. How these changes link to simplistic cognitive behavioural
      ideologies of health promotion and rational decision-making is explored.
      Utilising two different empirical studies, this article highlights how self
      management and expected compliance with governmental authority in relation to
      health practices position not only communities that experience multiple
      disadvantage but also more seemingly privileged social actors. The article
      presents a challenge to self-management and informed choice, in which the
      importance of navigational networks is evident. Because health care can become
      remote and inaccessible to certain sections of the community, yet pervasive and
      deterministic for others, we need multiple levels of analysis and different forms
      of action. 

PMID- 24443921
TI  - Working memory affects older adults' use of context in spoken-word recognition.
AB  - Many older listeners report difficulties in understanding speech in noisy
      situations. Working memory and other cognitive skills may modulate older
      listeners' ability to use context information to alleviate the effects of noise
      on spoken-word recognition. In the present study, we investigated whether verbal
      working memory predicts older adults' ability to immediately use context
      information in the recognition of words embedded in sentences, presented in
      different listening conditions. In a phoneme-monitoring task, older adults were
      asked to detect as fast and as accurately as possible target phonemes in
      sentences spoken by a target speaker. Target speech was presented without noise,
      with fluctuating speech-shaped noise, or with competing speech from a single
      distractor speaker. The gradient measure of contextual probability (derived from
      a separate offline rating study) affected the speed of recognition. Contextual
      facilitation was modulated by older listeners' verbal working memory (measured
      with a backward digit span task) and age across listening conditions. Working
      memory and age, as well as hearing loss, were also the most consistent predictors
      of overall listening performance. Older listeners' immediate benefit from context
      in spoken-word recognition thus relates to their ability to keep and update a
      semantic representation of the sentence content in working memory. 

PMID- 24443922
TI  - On the fate of sexual traits under asexuality.
AB  - Environmental shifts and life-history changes may result in formerly adaptive
      traits becoming non-functional or maladaptive. In the absence of pleiotropy and
      other constraints, such traits may decay as a consequence of neutral mutation
      accumulation or selective processes, highlighting the importance of natural
      selection for adaptations. A suite of traits are expected to lose their adaptive
      function in asexual organisms derived from sexual ancestors, and the many
      independent transitions to asexuality allow for comparative studies of parallel
      trait maintenance versus decay. In addition, because certain traits, notably male
      specific traits, are usually not exposed to selection under asexuality, their
      decay would have to occur as a consequence of drift. Selective processes could
      drive the decay of traits associated with costs, which may be the case for the
      majority of sexual traits expressed in females. We review the fate of male and
      female sexual traits in 93 animal lineages characterized by asexual reproduction,
      covering a broad taxon range including molluscs, arachnids, diplopods,
      crustaceans and eleven different hexapod orders. Many asexual lineages are still
      able occasionally to produce males. These asexually produced males are often
      largely or even fully functional, revealing that major developmental pathways can
      remain quiescent and functional over extended time periods. By contrast, for
      asexual females, there is a parallel and rapid decay of sexual traits, especially
      of traits related to mate attraction and location, as expected given the
      considerable costs often associated with the expression of these traits. The
      level of decay of female sexual traits, in addition to asexual females being
      unable to fertilize their eggs, would severely impede reversals to sexual
      reproduction, even in recently derived asexual lineages. More generally, the
      parallel maintenance versus decay of different trait types across diverse asexual
      lineages suggests that neutral traits display little or no decay even after
      extended periods under relaxed selection, while extensive decay for selected
      traits occurs extremely quickly. These patterns also highlight that adaptations
      can fix rapidly in natural populations of asexual organisms, in spite of their
      mode of reproduction. 

PMID- 24443923
TI  - Assessment of ospemifene or lubricants on clinical signs of VVA.
AB  - INTRODUCTION: Ospemifene is a new oral estrogen receptor agonist/antagonist with
      tissue-selective effects approved for the treatment of moderate to severe
      dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy (VVA). AIM:
      The aim of the study is to assess ospemifene or lubricant use on the clinical
      signs of VVA. METHODS: Subjects in three double-blind, placebo-controlled
      clinical trials were randomized to ospemifene or placebo. In two of the trials,
      women were provided nonhormonal lubricants for use as needed, and a preplanned
      evaluation of the frequency of lubricant use was performed. Additionally, a post
      hoc placebo group analysis for impact of lubricant use or nonuse on physiologic
      effects of the percentage of superficial and parabasal cells (maturation index)
      and vaginal pH was conducted. A secondary preplanned end point included visual
      examination of the vagina (clinical signs of vaginal dryness, petechiae, pallor,
      friability, and redness of the mucosa) comparing change from baseline to end of
      treatment for the ospemifene 60-mg/day group and vs. placebo. MAIN OUTCOME
      MEASURES: The primary end points in the phase 3 clinical trials included the
      percentage of superficial cells, parabasal cells, vaginal pH, and most bothersome
      symptoms compared with placebo. RESULTS: There was no significant difference in
      physiologic effects between placebo lubricant users vs. nonusers in either 12
      week study. Compared with baseline, substantially more subjects receiving
      ospemifene 60 mg/day than placebo showed complete resolution of clinical signs of
      VVA after 12 and 52 weeks of treatment. CONCLUSIONS: Ospemifene substantially
      improved clinical signs of VVA. Within the placebo group, there was no difference
      in physiologic effects in lubricant users vs. nonusers. Based on gynecologic
      evaluation of the vagina, benefits were apparent at 12 weeks and sustained for 52
      weeks in the ospemifene-treated subjects with significant improvement over
      placebo. In these three clinical trials, in contrast to ospemifene-treated women,
      placebo subjects who utilized lubricants had no improvement in their underlying
      vaginal physiology.

PMID- 24443924
TI  - Association of XPD Lys751Gln polymorphism with head and neck cancer
      susceptibility: evidence from 11,443 subjects.
AB  - BACKGROUND: Whether the single nucleotide polymorphism (SNP) Lys751Gln of
      xeroderma pigmentosum group D(XPD) gene increases susceptibility to head and neck
      cancer (HNC) is controversial and undetermined. Therefore, we conducted this meta
      analysis to systematically assess the possible association between them. METHODS:
      The OVID, Medline, Embase, Pubmed, Web of Science databases were searched to
      identify the eligible studies. The odds ratio (OR) with 95% confidence interval
      (95% CI) were used to assess the strength of association. RESULTS: A total of
      11,443 subjects from eighteen studies were subjected to meta-analysis. Overall,
      XPD Lys751Gln polymorphism had no association with increased HNC risk under all
      five genetic models (P > 0.05). In the subgroup analysis by ethnicity and source
      of controls, still no significant association was found under five genetic models
      (P > 0.05). In the subgroup analysis by cancer type, XPD Lys751Gln polymorphism
      had statistically significant association with elevated laryngeal cancer (LC) and
      nasopharyngeal cancer (NPC) risk under heterozygous comparison and dominant model
      (P<0.05) and borderline significantly increased risk was found under allele
      contrast for LC and NPC. Carriers of Lys allele and Lys/Lys genotype may be
      associated with elevated LC and NPC risk. CONCLUSIONS: There is overall lack of
      association between XPD Lys751Gln polymorphism and HNC risk under all five
      genetic models and still no significant association was found in the subgroup
      analysis by ethnicity and source of controls. However, XPD Lys751Gln polymorphism
      was significantly associated with susceptibility to LC and NPC and the Lys allele
      and Lys/Lys genotype of XPD Lys751Gln polymorphism may be a risk factor for LC
      and NPC. However, relatively modest sample sizes were included in this meta
      analysis and studies with large sample sizes and representative population are
      warranted to further clarify this finding. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5628716106316015.

PMID- 24443925
TI  - Understanding the temporal evolution of neuronal connectivity in cultured
      networks using statistical analysis.
AB  - BACKGROUND: Micro-Electrode Array (MEA) technology allows researchers to perform
      long-term non-invasive neuronal recordings in-vitro while actively interacting
      with the cultured neurons. Despite numerous studies carried out using MEAs, many
      functional, chemical and structural mechanisms of how dissociated cortical
      neurons develop and respond to external stimuli are not yet well understood
      because of the lack of quantitative studies that assess how their development can
      be affected by chronic external stimulation. METHODS: To investigate network
      changes, we analyzed a large MEA data set composed of neuron spikes recorded from
      cultures of dissociated rat cortical neurons plated on MEA dishes with 59
      recording electrodes each. Neural network activity was recorded during the first
      five weeks of each culture's in-vitro development. Stimulation sessions were
      delivered to each of the 59 electrodes. The False Discovery Rate technique was
      used to quantify the temporal evolution of dissociated cortical neurons. Our
      analysis focused on network responses that occurred within selected time window
      durations, namely 50 ms, 100 ms and 150 ms after stimulus onset. RESULTS: Our
      results show an evolution in dissociated cortical neuronal network activity over
      time, that reflects the network synaptic evolution. Furthermore, we tested the
      sensitivity of our technique to different observation time windows and found that
      varying the time windows, allows us to capture different dynamics of the observed
      responses. In addition, when selecting a 150 ms observation time window, our
      findings indicate that cultures dissociated from the same brain tissue display
      trends in their temporal evolution that are more similar than those obtained from
      different brains. CONCLUSION: Our results emphasize that the FDR technique can be
      implemented without the need to make any particular assumptions about the data a
      priori. The proposed technique was able to capture the well-known dissociated
      cortical neuron networks' temporal evolution, that has been previously observed
      in in-vivo and in intact brain tissue studies. Furthermore, our findings suggest
      that the time window that is used to capture the stimulus-evoked network
      responses is a critical parameter to analyze the electrical behavioral and
      temporal evolution of dissociated cortical neurons.

PMID- 24443926
TI  - Telephotography in trauma: a 2-year clinical experience.
AB  - INTRODUCTION: Smartphones can be used to record and transmit high-quality
      clinical photographs. The aim of this study was to describe our experience with
      smartphone telephotography in the care of trauma patients. We hypothesized that
      smartphone telephotography can be safely and effectively implemented on a trauma
      service. SUBJECTS AND METHODS: We performed a 2-year (January 2011-December 2012)
      prospective analysis of all patient photographs recorded by members of our trauma
      team at our Level I trauma center. All members of the trauma team recorded
      patient photographs and e-mailed them to a secure e-mail account. An
      administrative assistant uploaded a copy of each photgrapho into the patient's
      electronic medical record. We assessed the number of photographs collected and
      uploaded, as well as the success, failure, and complication rates. RESULTS: Our
      trauma team sent 7,200 photographs to a secure e-mail account. Of those, 6,120
      (85%) were considered, after an initial review, to be of good quality. Of these,
      3,320 photographs (54%) were successfully uploaded into a patient's electronic
      medical record; the remaining 2,800 photographs lacked adequate labeling and
      could not be uploaded. The average interval to uploading was 3 months. In total,
      10 photographs were uploaded into the wrong patient's electronic medical record,
      for an error rate of 0.003%. We received only three complaints during the study
      period. CONCLUSIONS: Telephotography can be safely and effectively implemented in
      trauma clinical practice. Fears of Health Insurance Portability and
      Accountability Act violations are not valid, as the incidence of patient
      complaints is minimal when telephotography is implemented under strict guidelines
      and rules. Dedicated administrative personnel are essential for effective
      implementation of smartphone photography.

PMID- 24443927
TI  - Impact of dysphagia severity on clinical decision making via telerehabilitation.
AB  - OBJECTIVE: Recent research supports the proposal that valid and reliable clinical
      swallow examinations (CSEs) can be conducted via telerehabilitation. However, no
      studies have explored whether dysphagia severity has an impact on the success of
      the session or its outcomes. The current study examined how dysphagia severity
      impacted on either (a) clinical decision making for safety of oral intake or (b)
      clinician perceptions of CSEs conducted via telerehabilitation. SUBJECTS AND
      METHODS: One hundred patients (25 nondysphagics and 25 mild, 25 moderate, and 25
      severe dysphagics) were assessed using a telehealth system and methodology
      reported in prior research. For each assessment, the online and face-to-face
      (FTF) clinicians simultaneously completed a structured CSE. On session
      completion, the online clinician indicated level of agreement with two statements
      regarding the level of rapport and ability to competently assess the patient.
      RESULTS: In each of the four groups, acceptable levels of agreement were observed
      between raters for the three primary outcomes (decisions regarding oral/nonoral
      intake and safe food and fluids) as well as over 90% of the CSE items. Clinicians
      agreed they could develop good rapport with the majority of patients in all
      groups. However, for a small but significant (p<0.5) proportion of patents in the
      severe dysphagic group, clinicians disagreed they were able to satisfactorily and
      competently assess to the best of their abilities using the telerehabilitation
      system. CONCLUSIONS: Clinical decisions made during and as an outcome of the
      total CSE were found to be comparable to those made in the FTF environment
      regardless of dysphagia severity. Clinicians noted some difficulty assessing
      patients with greater complexity, which occurred in greater numbers in the group
      with severe dysphagia.

PMID- 24443928
TI  - Patient education self-management during surgical recovery: combining mobile
      (iPad) and a content management system.
AB  - OBJECTIVE: The objective of this investigation was to assess whether a new
      electronic health (e-health) platform, combining mobile computing and a content
      management system, could effectively deliver modular and "just-in-time" education
      to older patients following cardiac surgery. SUBJECTS AND METHODS: Patients were
      provided with iPad((r)) (Apple((r)), Cupertino, CA) tablets that delivered
      educational modules as part of a daily "to do" list in a plan of care. The tablet
      communicated wirelessly to a dashboard where data were aggregated and displayed
      for providers. RESULTS: A surgical population of 149 patients with a mean age of
      68 years utilized 5,267 of 6,295 (84%) of education modules delivered over a 5.3
      day hospitalization. Increased age was not associated with decreased use.
      CONCLUSIONS: We demonstrate that age, hospitalization, and major surgery are not
      significant barriers to effective patient education if content is highly
      consumable and relevant to patients' daily care experience. We also show that
      mobile technology, even if unfamiliar to many older patients, makes this
      possible. The combination of mobile computing with a content management system
      allows for dynamic, modular, personalized, and "just-in-time" education in a
      highly consumable format. This approach presents a means by which patients may
      become informed participants in new healthcare models.

PMID- 24443929
TI  - Biophysical groundwork as a hinge to unravel the biology of alpha-synuclein
      aggregation and toxicity.
AB  - Alpha-synuclein (aS) and its aggregation properties are central in the
      development and spread of Parkinson's disease. Point mutations and
      multiplications of the SNCA gene encoding aS cause autosomal dominant forms of
      the disorder. Moreover, protein inclusions found in the surviving neurons of
      parkinsonian brains consist mainly of a fibrillar form of aS. Aggregates of aS,
      which form a transient, complex and heterogeneous ensemble, participate in a wide
      variety of toxic mechanisms that may be amplified by aS spreading among
      neighbouring neurons. Recently, significant effort has been directed into the
      study of the aS aggregation process and the impact of aS aggregates on neuron
      survival. In this review, we present state-of-the-art biophysical studies on the
      aS aggregation process in vitro and in cellular models. We comprehensively review
      the new insights generated by the recent biophysical investigations, which could
      provide a solid basis from which to design future biomedical studies. The diverse
      cellular models of aS toxicity and their potential use in the biophysical
      investigation are also discussed. 

PMID- 24443931
TI  - A preliminary report on the English phonology of typically developing English
      Mandarin bilingual preschool Singaporean children.
AB  - BACKGROUND: There are no published data on typical phonological development for
      Singaporean children. There is therefore the risk that children's speech in
      Singapore may be misdiagnosed or that clinicians may set goals erroneously. AIMS:
      This paper reports a preliminary study on the English phonology of typically
      developing 4;0-4;5-year-old Chinese Singaporean children who speak English and
      Mandarin. METHOD & PROCEDURES: Seventy children were recruited throughout
      Singapore, and speech samples were collected in English using the Phonology
      Assessment of the Diagnostic Evaluation of Articulation and Phonology (DEAP). The
      participants were divided equally into two groups: English-dominant and Mandarin
      dominant. Their speech samples were compared with British English targets (BT)
      and Singapore English targets (ST) in terms of phonological accuracy and types of
      phonological processes used. OUTCOMES & RESULTS: The results showed that
      Singaporean children's phonological accuracy scores increased significantly when
      scored against ST instead of BT. When scored against ST, English-dominant
      children were found to perform similarly to their DEAP counterparts. However,
      Mandarin-dominant children had significantly less accurate consonant production
      in English and exhibited more interference effects from Mandarin phonology than
      English-dominant children. CONCLUSIONS & IMPLICATIONS: In this preliminary study,
      the results highlight the importance of speech and language therapists using
      local dialect pronunciations to be the target of speech assessments so as to
      provide appropriate assessment and intervention. It is also essential to account
      for the language background and language dominance of the children. More local
      normative data are needed for the typical acquisition of Singapore English in
      children, especially for children whose dominant language is not English.

PMID- 24443930
TI  - Long acting contraception provision by rural primary care physicians.
AB  - OBJECTIVES: Unplanned pregnancy is a public health problem in the United States,
      including in rural areas. Primary care physicians are the main providers of
      health care to women in rural areas and are uniquely positioned to help reduce
      unplanned pregnancy in rural women. This study documents provision of
      contraception by rural primary care physicians, focusing on the most effective,
      long acting methods, intrauterine devices (IUDs) and contraceptive implants.
      METHODS: We surveyed all primary care physicians practicing in rural areas of
      Illinois and Wisconsin. Bivariate analysis was performed using chi squared and
      Fisher's exact test, and multivariable analysis was performed with logistic
      regression to determine factors associated with provision. RESULTS: The response
      rate was 862 out of 2312 physicians (37%). Nine percent of respondents place
      implants and 35% place IUDs. Eighty-seven percent of physicians had not had
      training in implant placement, and 41% had not had training in IUD placement. In
      multivariable analysis, factors associated with placement of long acting
      contraception include provision of maternity care, and female gender of the
      physician. The most common reasons for not providing the methods were lack of
      training and perceived low demand from patients. CONCLUSIONS: Many rural primary
      care providers do not place long acting contraceptive devices due to lack of
      training. Female physicians and those providing maternity care are the most
      likely to place these devices. Increased training for primary care physicians
      both during and after residency would help increase access to these options for
      women in rural areas.

PMID- 24443932
TI  - Distribution and excretion of perfluorooctane sulfonate (PFOS) in beef cattle
      (Bos taurus).
AB  - Perfluorooctane sulfonate (PFOS), a perfluoroalkyl surfactant used in many
      industrial products, is present in industrial wastes and in wastewater treatment
      plant biosolids. Biosolids are commonly applied to pastures and crops used for
      animal feed; consequently, PFOS may accumulate in the edible tissues of grazing
      animals or in animals exposed to contaminated feeds. There are no data on the
      absorption, distribution, and excretion of PFOS in beef cattle, so a 28-day study
      was conducted to determine these parameters for PFOS in three Lowline Angus
      steers given a single oral dose of PFOS at approximately 8 mg/kg body weight.
      PFOS concentrations were determined by liquid chromatography-tandem mass
      spectrometry in multiple tissue compartments. The major route of excretion was in
      the feces (11 +/- 1.3% of the dose, mean +/- standard deviation) with minimal
      PFOS elimination in urine (0.5 +/- 0.07% of the dose). At day 28 the mean plasma
      concentration remained elevated at 52.6 +/- 3.4 MUg/mL, and it was estimated that
      35.8 +/- 4.3% of the dose was present in the plasma. Plasma half-lives could not
      be calculated due to multiple peaks caused by apparent redistributions from other
      tissues. These data indicate that after an acute exposure PFOS persists and
      accumulates in edible tissues. The largest PFOS body burdens were in the blood
      (~36%), carcass remainder (5.7 +/- 1.6%), and the muscle (4.3 +/- 0.6%). It was
      concluded that PFOS would accumulate in edible tissues of beef, which could be a
      source of exposure for humans. 

PMID- 24443933
TI  - A role of ADAR2 and RNA editing of glutamate receptors in mood disorders and
      schizophrenia.
AB  - BACKGROUND: Pre-mRNAs of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)-propanoic
      acid (AMPA)/kainate glutamate receptors undergo post-transcriptional modification
      known as RNA editing that is mediated by adenosine deaminase acting on RNA type 2
      (ADAR2). This modification alters the amino acid sequence and function of the
      receptor. Glutamatergic signaling has been suggested to have a role in mood
      disorders and schizophrenia, but it is unknown whether altered RNA editing of
      AMPA/kainate receptors has pathophysiological significance in these mental
      disorders. In this study, we found that ADAR2 expression tended to be decreased
      in the postmortem brains of patients with schizophrenia and bipolar disorder.
      RESULTS: Decreased ADAR2 expression was significantly correlated with decreased
      editing of the R/G sites of AMPA receptors. In heterozygous Adar2 knockout mice
      (Adar2+/- mice), editing of the R/G sites of AMPA receptors was decreased.
      Adar2+/- mice showed a tendency of increased activity in the open-field test and
      a tendency of resistance to immobility in the forced swimming test. They also
      showed enhanced amphetamine-induced hyperactivity. There was no significant
      difference in amphetamine-induced hyperactivity between Adar2+/- and wild type
      mice after the treatment with an AMPA/kainate receptor antagonist, 2,3-dihydroxy
      6-nitro-7-sulfamoyl-benzo[f]quinoxaline. CONCLUSIONS: These findings collectively
      suggest that altered RNA editing efficiency of AMPA receptors due to down
      regulation of ADAR2 has a possible role in the pathophysiology of mental
      disorders.

PMID- 24443934
TI  - Role of LONELY GUY genes in indeterminate nodulation on Medicago truncatula.
AB  - LONELY GUY (LOG) genes encode cytokinin riboside 5'-monophosphate
      phosphoribohydrolases and are directly involved in the activation of cytokinins.
      To assess whether LOG proteins affect the influence of cytokinin on nodulation,
      we studied two LOG genes of Medicago truncatula. Expression analysis showed that
      MtLOG1 and MtLOG2 were upregulated during nodulation in a CRE1-dependent manner.
      Expression was mainly localized in the dividing cells of the nodule primordium.
      In addition, RNA interference revealed that MtLOG1 is involved in nodule
      development and that the gene plays a negative role in lateral root development.
      Ectopic expression of MtLOG1 resulted in a change in cytokinin homeostasis,
      triggered cytokinin-inducible genes and produced roots with enlarged vascular
      tissues and shortened primary roots. In addition, those 35S:LOG1 roots also
      displayed fewer nodules than the wild-type. This inhibition in nodule formation
      was local, independent of the SUPER NUMERIC NODULES gene, but coincided with an
      upregulation of the MtCLE13 gene, encoding a CLAVATA3/EMBRYO SURROUNDING REGION
      peptide. In conclusion, we demonstrate that in M. truncatula LOG proteins might
      be implicated in nodule primordium development and lateral root formation. 

PMID- 24443935
TI  - Tongue-mandible coupling movements during saliva swallowing.
AB  - The purpose of this study was to measure the tongue and mandible positions and
      displacements in relation to the maxilla in the midsagittal plane to characterize
      the different saliva swallowing patterns by recording their kinematics. A 2D
      electromagnetic articulograph using four transducer coils, three attached to the
      upper surface of the tongue midline plus one attached to the chin anterior part
      allowed continuous evaluation of tongue and chin movements in twelve young adults
      in good general health. During 170 s sequences recorded at a frequency of 100 Hz,
      subjects were at rest, silently reading a text they had chosen. The subjects were
      free to swallow during the sequence. Deglutition of accumulated saliva was
      analysed after averaging all values obtained during successive 250 ms periods. We
      identified three elementary swallowing patterns. Mean duration of tongue-mandible
      movements were 1.51 +/- 0.17 s, 1.63 +/- 0.14 s and 2.00 +/- 0.08 s for the
      first, second and third patterns respectively. In the light of other studies
      based on intra-oral pressure recordings, our results help to understand the
      tongue-mandible coupling behaviours involved in managing an in-mouth saliva bolus
      during the three elementary swallowing patterns identified. 

PMID- 24443936
TI  - Efficacy of family mediation and the role of family violence: study protocol.
AB  - BACKGROUND: Family law reforms in Australia require separated parents in dispute
      to attempt mandatory family dispute resolution (FDR) in community-based family
      services before court attendance. However, there are concerns about such services
      when clients present with a history of high conflict and family violence. This
      study protocol describes a longitudinal study of couples presenting for family
      mediation services. The study aims to describe the profile of family mediation
      clients, including type of family violence, and determine the impact of violence
      profiles on FDR processes and outcomes, such as the type and durability of shared
      parenting arrangements and clients' satisfaction with mediated agreements.
      METHODS: A mixed method, naturalistic longitudinal design is used. The sampling
      frame is clients presenting at nine family mediation centres across metropolitan,
      outer suburban, and regional/rural sites in Victoria, Australia. Data are
      collected at pre-test, completion of mediation, and six months later. Self
      administered surveys are administered at the three time points, and a telephone
      interview at the final post-test. The key study variable is family violence. Key
      outcome measures are changes in the type and level of acrimony and violent
      behaviours, the relationship between violence and mediated agreements, the
      durability of agreements over six months, and client satisfaction with mediation.
      DISCUSSION: Family violence is a major risk to the physical and mental health of
      women and children. This study will inform debates about the role of family
      violence and how to manage it in the family mediation context. It will also
      inform decision-making about mediation practices by better understanding how
      mediation impacts on parenting agreements, and the implications for children,
      especially in the context of family violence.

PMID- 24443938
TI  - Identification and quantification of in vivo metabolites of 9,10
      phenanthrenequinone in human urine associated with producing reactive oxygen
      species.
AB  - Polycyclic aromatic hydrocarbon quinones (PAHQs) are components in airborne
      particulate matter (PM) and generate reactive oxygen species (ROS) in a redox
      cycling process. 9,10-Phenanthrenequinone (9,10-PQ) is a PAHQ found in diesel
      exhaust particulates and PM. When inhaled, it produces much more ROS than other
      PAHQs. We hypothesized that urinary metabolites of 9,10-PQ could serve as
      biomarkers of PAHQ exposure. Here, we describe methods for pretreating urine
      samples and analyzing 9,10-PQ metabolites by liquid chromatography with tandem
      mass spectrometry (LC-MS/MS). In urine from rats intraperitoneally injected with
      9,10-PQ, the monoglucuronide of 9,10-dihydroxyphenanthrene (9,10-PQHG) was found
      to be a major metabolite of 9,10-PQ. 9,10-PQHG was also identified in the urine
      of a nonoccupationally exposed human by its retention time and MS/MS spectra.
      Furthermore, the urine contained hardly any free (unmetabolized) 9,10-PQ, but
      treating it with hydrolytic enzymes released 9,10-PQ from conjugated metabolites
      such as 9,10-PQHG. The concentrations of 9,10-PQHG in urine samples from
      nonoccupationally exposed subjects who lived in a suburban area were 2.04-19.08
      nmol/mol creatinine. This study is the first to demonstrate the presence of 9,10
      PQHG in human urine. Determination of urinary 9,10-PQHG should be useful for
      determining 9,10-PQ exposure. 

PMID- 24443939
TI  - Exploring the physicochemical properties of oxime-reactivation therapeutics for
      cyclosarin, sarin, tabun, and VX inactivated acetylcholinesterase.
AB  - The inactivation of acetylcholinesterase (AChE) by organophosphorus agent (OP)
      compounds is a serious problem regardless of how the individual was exposed. The
      reactivation of OP-inactivated AChE is dependent on the OP conjugate, and
      commonly a specific oxime is better at reactivating a specific OP conjugate than
      several diverse OP conjugates. The presented research explores the
      physicochemical properties needed for the reactivation of OP-inactivated AChE.
      Four different OPs, cyclosarin, sarin, tabun, and VX, were analyzed using the
      same set of oxime reactivators. A trial descriptor pool of semiempirical,
      traditional, and molecular interaction field descriptors was used to construct an
      ensemble of QSAR models for each OP-conjugate pair. Based on the molecular
      information and the cross-validation ability, individual QSAR models were
      selected to be part of an OP-conjugate consensus model. The OP-conjugate specific
      models provide important insight into the physicochemical properties required to
      reactivate the OP conjugates of interest. The reactivation of AChE inactivated
      with either cyclosarin or tabun requires the oxime therapeutic to possess an
      overall polar-positive surface area. Oxime therapeutics for the reactivation of
      sarin-inactivated AChE are conformationally dependent while oxime reverse
      therapeutics for VX require a compact region with a highly hydrophilic region and
      two positively charged pyridine rings. 

PMID- 24443941
TI  - Visualization of electrode-electrolyte interfaces in LiPF6/EC/DEC electrolyte for
      lithium ion batteries via in situ TEM.
AB  - We report direct visualization of electrochemical lithiation and delithiation of
      Au anodes in a commercial LiPF6/EC/DEC electrolyte for lithium ion batteries
      using transmission electron microscopy (TEM). The inhomogeneous lithiation,
      lithium metal dendritic growth, electrolyte decomposition, and solid-electrolyte
      interface (SEI) formation are observed in situ. These results shed lights on
      strategies of improving electrode design for reducing short-circuit failure and
      improving the performance of lithium ion batteries. 

PMID- 24443940
TI  - CARD11 blockade suppresses murine collagen-induced arthritis via inhibiting
      CARD11/Bcl10 assembly and T helper type 17 response.
AB  - The scaffold protein caspase recruitment domain-containing protein 11 (CARD11) is
      implicated in the regulation of inflammation and autoimmunity. The present study
      aimed to explore the role of CARD11 in the pathogenesis of rheumatoid arthritis
      (RA). Mice with collagen-induced arthritis (CIA) were treated with either CARD11
      targeted interfering RNA (CARD11 siRNA) or control siRNA by intraperitoneal
      injection every 3 days after CIA establishment. The clinical score of arthritis
      was recorded every other day. Synovial inflammation and cartilage erosion were
      evaluated by histology and microcomputed tomography (micro-CT). Serum anti-type
      II collagen (anti-CII) antibodies and cytokines were measured by enzyme-linked
      immunosorbent assay (ELISA). The CARD11/Bcl10 formation and nuclear factor-kappa
      B (NF-kappaB) activation was assessed by immunoprecipitation and immunoblotting,
      and the percentage of T helper type 17 (Th17) cells was determined by flow
      cytometry. Systemic administration of CARD11 siRNA significantly reduced the
      clinical score of CIA severity. As indicated by the histology, joint inflammation
      and destruction were attenuated by CARD11 siRNA treatment. Micro-CT demonstrated
      less severe joint destruction in CARD11 siRNA-treated mice than in control mice.
      CARD11 siRNA treatment resulted in inhibition of CARD11/Bcl10 formation and the
      subsequent NF-kappaB activation. In addition, treatment with CARD11 siRNA
      resulted in a pronounced decrease in proinflammatory cytokines interleukin (IL)
      1beta, IL-6 and IL-17. Serum anti-CII antibody and the percentage of Th17 cells
      were also significantly reduced. CARD11 is involved in the pathogenesis of CIA by
      formation of the CARD11/Bcl10 complex and enhancement of the Th17 cell response.
      Targeting CARD11 provides a novel research direction in the development of
      therapeutic strategies for RA. 

PMID- 24443942
TI  - Exploration of dimensionality and psychometric properties of the Pittsburgh Sleep
      Quality Index in cases with temporomandibular disorders.
AB  - BACKGROUND: This study assessed the dimensional structure of sleep quality with
      the Pittsburgh Sleep Quality Index (PSQI) and investigated its psychometric
      properties in cases with temporomandibular disorders (TMD). METHODS: A
      convenience sample of 609 TMD cases (age: 37.1 +/- 13.1 yrs, 18-67 yrs, 85%
      female) of the multi-center Validation Project meeting Research Diagnostic
      Criteria for Temporomandibular Disorders (RDC/TMD) and with sufficient PSQI data
      were included in this study. To investigate PSQI scores' dimensionality,
      exploratory factor analysis was used. Factors were identified using the Scree
      plot. To investigate internal consistency, Cronbach's alpha was calculated.
      Analyses were separately performed for TMD cases with (N = 496) and TMD cases
      withouta pain-related diagnosis (N = 113). RESULTS: The mean PSQI score for all
      TMD cases was 7.1 +/- 4.0 units, range: 0-19. The exploratory factor analysis
      identified one factor for cases with at least one pain-related TMD diagnosis as
      well as one factor for cases with a pain-free TMD diagnosis that explained 41% of
      the variance in cases with pain-related TMD and 37% in cases with pain-free TMD.
      Internal consistency for PSQI scores was alpha of 0.75 in cases with pain-related
      TMD, alpha of 0.66 in cases with pain-free TMD and alpha = 0.75 for all TMD
      cases. CONCLUSIONS: Sleep quality in TMD patients is a unidimensional construct
      and can therefore be represented by one summary score; a finding that is in line
      with previous reports in TMD patients.

PMID- 24443943
TI  - Testosterone replacement therapy following the diagnosis of prostate cancer:
      outcomes and utilization trends.
AB  - INTRODUCTION: Late-onset hypogonadism may impair quality of life and contribute
      to metabolic and cardiovascular comorbidity in aging men. Testosterone
      replacement therapy is effective in treating hypogonadism. However, for the
      millions of men with a history of prostate cancer, exogenous testosterone has
      long been considered contraindicated, even though little data in such men are
      available. Clarification of this safety issue could allow treatment to be
      considered for a sizeable segment of the aging male population. AIM: The aim of
      this study is to examine population-based utilization and impact of testosterone
      replacement therapy in men with prostate cancer. METHODS: Using linked
      Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354
      men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men
      received exogenous testosterone following their cancer diagnosis. We used
      propensity scoring analysis to examine the effect of testosterone replacement on
      the use of salvage hormone therapy and overall and prostate cancer-specific
      mortality. MAIN OUTCOME MEASURES: We assessed overall mortality, cancer-specific
      mortality, and the use of salvage hormone therapy. RESULTS: Following prostate
      cancer diagnosis, testosterone replacement was directly related to income and
      educational status and inversely related to age (all P < 0.001). Men undergoing
      radical prostatectomy and men with well-differentiated tumors were more likely to
      receive testosterone (all P < 0.001). On adjusted analysis, testosterone
      replacement therapy was not associated with overall or cancer-specific mortality
      or with the use of salvage hormone therapy. CONCLUSIONS: In this population-based
      observational study of testosterone replacement therapy in men with a history of
      prostate cancer, treatment was not associated with increased overall or cancer
      specific mortality. These findings suggest testosterone replacement therapy may
      be considered in men with a history of prostate cancer, but confirmatory
      prospective studies are needed.

PMID- 24443944
TI  - Edward E. Mason.

PMID- 24443945
TI  - Importance and performance of managerial skills in the Australian aged care
      sector - a middle managers' perspective.
AB  - AIM: This study examined the importance and performance of middle managers'
      skills to provide a starting point for a sector-wide leadership and management
      framework. BACKGROUND: There is an increasing consensus that the quality of
      management, leadership and performance of any organisation is directly linked to
      the capabilities of its middle managers and the preparation and on-going training
      they receive. METHOD: A total of 199 middle managers from three aged care
      organisations in Australia participated in a questionnaire conducted during 2010
      2011. RESULT: This study found that middle managers perceived the need to develop
      their communication skills, self-awareness, change management, conflict
      resolution and leadership skills. CONCLUSION: Middle managers perceive a
      discrepancy between performance and importance of various managerial skills. This
      study demonstrated that provision of training needs to go beyond clinical skills
      development and further investigation into managers' needs is necessary,
      particularly considering the diversity of this critical group in organisations.
      IMPLICATIONS FOR NURSING MANAGEMENT: Future training opportunities provided to
      middle managers need to address the 'softer' skills (e.g. communication) rather
      than 'technical' skills (e.g. clinical skills). The provision of training in
      these skills may improve their performance, which may also lead to increased job
      satisfaction, continuity in leadership and management and ultimately improvements
      in the quality of care provided.

PMID- 24443946
TI  - Role of Go/i subgroup of G proteins in olfactory signaling of Drosophila
      melanogaster.
AB  - Intracellular signaling in insect olfactory receptor neurons remains unclear,
      with both metabotropic and ionotropic components being discussed. Here, we
      investigated the role of heterotrimeric Go and Gi proteins using a combined
      behavioral, in vivo and in vitro approach. Specifically, we show that inhibiting
      Go in sensory neurons by pertussis toxin leads to behavioral deficits. We
      heterologously expressed the olfactory receptor dOr22a in human embryonic kidney
      cells (HEK293T). Stimulation with an odor led to calcium influx, which was
      amplified via calcium release from intracellular stores. Subsequent experiments
      indicated that the signaling was mediated by the Gbetagamma subunits of the
      heterotrimeric Go/i proteins. Finally, using in vivo calcium imaging, we show
      that Go and Gi contribute to odor responses both for the fast (phasic) as for the
      slow (tonic) response component. We propose a transduction cascade model
      involving several parallel processes, in which the metabotropic component is
      activated by Go and Gi , and uses Gbetagamma. 

PMID- 24443947
TI  - Preliminary safety evaluation of photodynamic therapy for blood purification: an
      animal study.
AB  - Photodynamic therapy (PDT) has been shown to inactivate blood-borne pathogenic
      microorganisms in vitro. The method may be used to purify blood in the body, kill
      pathogenic microorganisms, and treat difficult diseases. Our aim was to
      investigate the safety of photodynamic blood purification (PBP) therapy using an
      in vivo blood circulation experiment in an animal model. Twenty-four New Zealand
      rabbits were used as experimental subjects; 12 received PDT and 12 served as
      negative controls. Extracorporeal blood bypass was established using the femoral
      artery and vein. A sterile disposable irradiation chamber was connected in the
      bypass pathway. Hematoporphyrin monomethyl ether was injected intravenously as a
      photosensitizer with an initial bolus of 3.7 mg, followed by a continuous
      infusion at 24 mg/h during PDT administration. Five minutes after initial
      injection, a laser beam was vertically focused on the irradiation chamber side
      wall, with a 9.5 cm(2) spot area, 1 h exposure time, and 20 mW/cm(2) power
      density. Six animals received a single PDT application, and six received PDT
      every other day for three applications. The 12 control group animals underwent
      extracorporeal blood circulation but did not receive the photosensitizer or light
      treatment. Blood samples were taken 20 min, 1 day, 4 days, and 7 days after PDT
      treatment for analysis of cell counts, coagulation, liver and renal function, and
      other biochemical changes. On the 7th day, animals were sacrificed, and
      parenchymal organs were evaluated for morphological changes. There were no
      significant differences in white blood cells, red blood cells, or
      destroyingplatelets after PDT compared with the control group. There was a little
      significant difference in alanine aminotransferase, aspartate aminotransferase,
      alkaline phosphatase, gamma-glutamyl transpeptidase, uric acid, blood urea
      nitrogen, and creatinine in the PDT group compared with the control group, except
      at individual time points. We found no significant damage in the heart, liver,
      spleen, lungs, kidneys, or other organs after PDT. This short-duration, fixed
      strength PBP method did not cause changes in blood parameters or in the structure
      or function of major organs in an animal model. These findings suggest that PBP
      is safe in vivo and has potential as a new therapy for inactivating blood-borne
      microorganisms. 

PMID- 24443948
TI  - Multifunctional antireflection coatings based on novel hollow silica-silica
      nanocomposites.
AB  - Antireflection (AR) coatings that exhibit multifunctional characteristics,
      including high transparency, robust resistance to moisture, high hardness, and
      antifogging properties, were developed based on hollow silica-silica
      nanocomposites. These novel nanocomposite coatings with a closed-pore structure,
      consisting of hollow silica nanospheres (HSNs) infiltrated with an acid-catalyzed
      silica sol (ACSS), were fabricated using a low-cost sol-gel dip-coating method.
      The refractive index of the nanocomposite coatings was tailored by controlling
      the amount of ACSS infiltrated into the HSNs during synthesis. Photovoltaic
      transmittance (TPV) values of 96.86-97.34% were obtained over a broad range of
      wavelengths, from 300 to 1200 nm; these values were close to the theoretical
      limit for a lossy single-layered AR coating (97.72%). The nanocomposite coatings
      displayed a stable TPV, with degradation values of less than 4% and 0.1% after
      highly accelerated temperature and humidity stress tests, and abrasion tests,
      respectively. In addition, the nanocomposite coatings had a hardness of
      approximately 1.6 GPa, while the porous silica coatings with an open-pore
      structure showed more severe degradation and had a lower hardness. The void
      fraction and surface roughness of the nanocomposite coatings could be controlled,
      which gave rise to near-superhydrophilic and antifogging characteristics. The
      promising results obtained in this study suggest that the nanocomposite coatings
      have the potential to be of benefit for the design, fabrication, and development
      of multifunctional AR coatings with both omnidirectional broadband transmission
      and long-term durability that are required for demanding outdoor applications in
      energy harvesting and optical instrumentation in extreme climates or humid
      conditions. 

PMID- 24443949
TI  - Two new proanthocyanidins from the leaves of Garcinia multiflora.
AB  - Two new proanthocyanidins, namely garcinianin A (1) and garcinianin B (2),
      together with two known compounds (3 and 4) were isolated from the leaves of
      Garcinia multiflora Champ. Their structures were elucidated on the basis of
      spectroscopic analysis. 

PMID- 24443950
TI  - A multicentric study regarding the use of hormone therapy during female mid-age
      (REDLINC VI).
AB  - BACKGROUND: Menopausal hormone therapy (HT) has shown benefits for women;
      however, associated drawbacks (i.e. risks, costs, fears) have currently
      determined its low use. OBJECTIVE: To determine the prevalence of current HT use
      among mid-aged women and describe the characteristics of those who have never
      used, have abandoned or are currently using HT. In addition, reasons for not
      using HT were analyzed. METHOD: This was a cross-sectional study that analyzed a
      total of 6731 otherwise healthy women (45-59 years old) of 15 cities in 11 Latin
      American countries. Participants were requested to fill out the Menopause Rating
      Scale (MRS) and a questionnaire containing sociodemographic data and items
      regarding the menopause and HT use. RESULTS: The prevalence of current HT use was
      12.5%. Oral HT (43.7%) was the most frequently used type of HT, followed by
      transdermal types (17.7%). The main factors related to the current use of HT
      included: positive perceptions regarding HT (odds ratio (OR) 11.53, 95%
      confidence interval (CI) 9.41-14.13), being postmenopausal (OR 3.47, 95% CI 2.75
      4.36) and having a better socioeconomic level. A total of 48.8% of surveyed women
      had used HT in the past, but abandoned it due to symptom improvement or being
      unconcerned; fear of cancer or any other secondary effects were also reported but
      in less than 10%. Among women who had never used HT, 28% reported the lack of
      medical prescription as the main reason, followed by the absence of symptoms
      (27.8%). Among those reporting lack of prescription as the main reason for not
      using HT, 30.6% currently had severe menopausal symptoms (total MRS score > 16);
      19.5% of women were using alternative 'natural' therapies, with 35.1% of them
      displaying severe menopausal symptoms as compared to a 22.5% observed among
      current HT users. CONCLUSION: The use of HT has not regained the rates observed a
      decade ago. Positive perceptions regarding HT were related to a higher use. Lack
      of medical prescription was the main reason for not using HT among non-users,
      many of whom were currently displaying severe menopausal symptoms.

PMID- 24443952
TI  - Management of biliary and pancreatic diseases using a new intraductal endoscope.
AB  - PURPOSE: We aimed to evaluate a new single-operator mini-endoscope for its
      performance, feasibility, and safety in the management of biliary and pancreatic
      diseases. PATIENTS AND METHODS: A retrospective analysis was conducted of 47
      patients (19 men; mean age, 50.3 years) who underwent cholangioscopy with the
      Polydiagnost (Pfaffenhofen, Germany) Polyscope device via various approaches for
      diagnosis and treatment of biliary and pancreatic diseases between January 2011
      and July 2012. RESULTS: Biliary pancreatic duct endoscopy was performed through a
      cystic duct, common bile duct, peroral, or sinus tract approach in 21, 9, 11, and
      6 patients, respectively. Thirty-two cases with bile duct stones were treated by
      basket extraction or complete stone fragmentation, 3 cases with tumor were
      treated by tissue ablation, and 4 cases with stricture were treated by stenting.
      Seven patients who were diagnosed with suspected stones preoperatively were
      excluded. No complications and morbidity associated with the use of biliary and
      pancreatic endoscopy was observed in this study. CONCLUSIONS: Cholangioscopy
      using the Polyscope system is a safe and effective technique for diagnosing or
      excluding biliary and pancreatic diseases (stone, strictures, or tumor).

PMID- 24443951
TI  - Reciprocal effects of parenting and borderline personality disorder symptoms in
      adolescent girls.
AB  - Theories of borderline personality disorder (BPD) postulate that high-risk
      transactions between caregiver and child are important for the development and
      maintenance of the disorder. Little empirical evidence exists regarding the
      reciprocal effects of parenting on the development of BPD symptoms in
      adolescence. The impact of child and caregiver characteristics on this reciprocal
      relationship is also unknown. Thus, the current study examines bidirectional
      effects of parenting, specifically harsh punishment practices and caregiver low
      warmth, and BPD symptoms in girls aged 14-17 years based on annual, longitudinal
      data from the Pittsburgh Girls Study (N = 2,451) in the context of child and
      caregiver characteristics. We examined these associations through the use of
      autoregressive latent trajectory models to differentiate time-specific variations
      in BPD symptoms and parenting from the stable processes that steadily influence
      repeated measures within an individual. The developmental trajectories of BPD
      symptoms and parenting were moderately associated, suggesting a reciprocal
      relationship. There was some support for time-specific elevations in BPD symptoms
      predicting subsequent increases in harsh punishment and caregiver low warmth.
      There was little support for increases in harsh punishment and caregiver low
      warmth predicting subsequent elevations in BPD symptoms. Child impulsivity and
      negative affectivity, and caregiver psychopathology were related to parenting
      trajectories, while only child characteristics predicted BPD trajectories. The
      results highlight the stability of the reciprocal associations between parenting
      and BPD trajectories in adolescent girls and add to our understanding of the
      longitudinal course of BPD in youth.

PMID- 24443955
TI  - A transcriptomics-based kinetic model for ethylene biosynthesis in tomato
      (Solanum lycopersicum) fruit: development, validation and exploration of novel
      regulatory mechanisms.
AB  - The gaseous plant hormone ethylene is involved in many physiological processes
      including climacteric fruit ripening, in which it is a key determinant of fruit
      quality. A detailed model that describes ethylene biochemistry dynamics is
      missing. Often, kinetic modeling is used to describe metabolic networks or
      signaling cascades, mostly ignoring the link with transcriptomic data. We have
      constructed an elegant kinetic model that describes the transfer of genetic
      information into abundance and metabolic activity of proteins for the entire
      ethylene biosynthesis pathway during fruit development and ripening of tomato
      (Solanum lycopersicum). Our model was calibrated against a vast amount of
      transcriptomic, proteomic and metabolic data and showed good descriptive
      qualities. Subsequently it was validated successfully against several ripening
      mutants previously described in the literature. The model was used as a
      predictive tool to evaluate novel and existing hypotheses regarding the
      regulation of ethylene biosynthesis. This bottom-up kinetic network model was
      used to indicate that a side-branch of the ethylene pathway, the formation of the
      dead-end product 1-(malonylamino)-1-aminocyclopropane-1-carboxylic acid (MACC),
      might have a strong effect on eventual ethylene production. Furthermore, our in
      silico analyses indicated potential (post-) translational regulation of the
      ethylene-forming enzyme ACC oxidase. 

PMID- 24443954
TI  - Nonmuscle myosin II is a critical regulator of clathrin-mediated endocytosis.
AB  - Variable requirements for actin during clathrin-mediated endocytosis (CME) may be
      related to regional or cellular differences in membrane tension. To compensate,
      local regulation of force generation may be needed to facilitate membrane curving
      and vesicle budding. Force generation is assumed to occur primarily through actin
      polymerization. Here we examine the role of myosin II using loss of function
      experiments. Our results indicate that myosin II acts on cortical actin scaffolds
      primarily in the plane of the plasma membrane (bottom arrow) to generate changes
      that are critical for enhancing CME progression. 

PMID- 24443957
TI  - Puberty as an accelerator for diabetes complications.
AB  - Much is written about how difficult it is to deal with diabetes during
      adolescence, and rightly so. Less is understood as to how puberty may be an
      accelerator of vascular complications. With the increase in childhood diabetes,
      complication risks need to be revisited in relation to puberty and the secular
      increase in adiposity. Recent data suggest greater risk for severe vascular
      complications in those with diabetes during puberty, compared with young people
      who develop diabetes after puberty. It is also widely recognized that higher
      hemoglobin A1c (HbA1c) results are often seen during the pubertal period. This
      article will review complication outcomes in relation to puberty and examine
      mechanisms by which puberty may modify risk above glycemic exposure, and possible
      gender disparities in the risk of complications in the adolescent period. 

PMID- 24443959
TI  - Photocatalysis deconstructed: design of a new selective catalyst for artificial
      photosynthesis.
AB  - A rapid increase in anthropogenic emission of greenhouse gases, mainly carbon
      dioxide, has been a growing cause for concern. While photocatalytic reduction of
      carbon dioxide (CO2) into solar fuels can provide a solution, lack of insight
      into energetic pathways governing photocatalysis has impeded study. Here, we
      utilize measurements of electronic density of states (DOS), using scanning
      tunneling microscopy/spectroscopy (STM/STS), to identify energy levels
      responsible for photocatalytic reduction of CO2-water in an artificial
      photosynthetic process. We introduce desired states in titanium dioxide (TiO2)
      nanoparticles, using metal dopants or semiconductor nanocrystals, and the
      designed catalysts were used for selective reduction of CO2 into hydrocarbons,
      alcohols, and aldehydes. Using a simple model, we provide insights into the
      photophysics governing this multielectron reduction and design a new composite
      photocatalyst based on overlapping energy states of TiO2 and copper indium
      sulfide (CIS) nanocrystals. These nanoparticles demonstrate the highest
      selectivity for ethane (>70%) and a higher efficiency of converting ultraviolet
      radiation into fuels (4.3%) using concentrated sunlight (>4 Sun illumination),
      compared with platinum-doped TiO2 nanoparticles (2.1%), and utilize hot electrons
      to tune the solar fuel from alkanes to aldehydes. These results can have
      important implications for the development of new inexpensive photocatalysts with
      tuned activity and selectivity. 

PMID- 24443956
TI  - Introduction to glycopathology: the concept, the tools and the perspectives.
AB  - Analyzing the flow of biological information is a fundamental challenge for basic
      sciences. The emerging results will then lend themselves to the development of
      new approaches for medical applications. Toward this end, the products of
      protein/lipid glycosylation deserve special attention. The covalent attachment of
      sugars to these carriers means much more than just a change of the carriers'
      physicochemical properties. In principle, the ubiquitous presence of
      glycoconjugates and the close inspection of the particular structural 'talents'
      of carbohydrates provide suggestive evidence for information coding by sugars. In
      fact, the theoretical number of 'words' (oligomers) formed by 'letters'
      (monosaccharides) is by far higher than by using nucleotides or amino acids. In
      other words, glycans harbor an unsurpassed coding capacity. The cyto- and
      histochemical detection of dynamic changes in the profile of cellular glycans
      (glycome, the equivalent of the proteome) by sugar receptors such as antibodies
      used as tools underscores the suitability of carbohydrates for such a task. The
      resulting staining patterns can be likened to a molecular fingerprint. By acting
      as ligand (counterreceptor) for endogenous receptors (tissue lectins), glycan
      epitopes become partners in a specific recognition pair, and the sugar-encoded
      information can then be translated into effects, e.g. in growth regulation. Of
      note, expression of both sides of such a pair, i.e. lectin and cognate glycan,
      can physiologically be orchestrated for optimal efficiency. Indeed, examples how
      to prevent autoimmune diseases by regulatory T cells and restrict carcinoma
      growth by a tumor suppressor attest occurrence of co-regulation. In consequence,
      these glycans have potential to establish a new class of functional biomarkers,
      and mapping presence of their receptors is warranted. In this review, the cyto-
      and histochemical methods, which contribute to explore information storage and
      transfer within the sugar code, are described. This introduction to the toolbox
      is flanked by illustrating the application of each type of tool in
      histopathology, with focus on adhesion/growth-regulating galectins. Together with
      an introduction to fundamental principles of the sugar code, the review is
      designed to guide into this field and to inspire respective research efforts.
      VIRTUAL SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1670639891114983.

PMID- 24443958
TI  - Transcranial direct current stimulation reduces the cost of performing a
      cognitive task on gait and postural control.
AB  - This proof-of-concept, double-blind study was designed to determine the effects
      of transcranial direct current stimulation (tDCS) on the 'cost' of performing a
      secondary cognitive task on gait and postural control in healthy young adults.
      Twenty adults aged 22 +/- 2 years completed two separate double-blind visits in
      which gait and postural control were assessed immediately before and after a 20
      min session of either real or sham tDCS (1.5 mA) targeting the left dorsolateral
      prefrontal cortex. Gait speed and stride duration variability, along with
      standing postural sway speed and area, were recorded under normal conditions and
      while simultaneously performing a serial-subtraction cognitive task. The dual
      task cost was calculated as the percent change in each outcome from normal to
      dual task conditions. tDCS was well tolerated by all subjects. Stimulation did
      not alter gait or postural control under normal conditions. As compared with sham
      stimulation, real tDCS led to increased gait speed (P = 0.006), as well as
      decreased standing postural sway speed (P = 0.01) and area (P = 0.01), when
      performing the serial-subtraction task. Real tDCS also diminished (P < 0.01) the
      dual task cost on each of these outcomes. No effects of tDCS were observed for
      stride duration variability. A single session of tDCS targeting the left
      dorsolateral prefrontal cortex improved the ability to adapt gait and postural
      control to a concurrent cognitive task and reduced the cost normally associated
      with such dual tasking. These results highlight the involvement of cortical brain
      networks in gait and postural control, and implicate the modulation of prefrontal
      cortical excitability as a potential therapeutic intervention.

PMID- 24443960
TI  - Cross sectional survey of human-bat interaction in Australia: public health
      implications.
AB  - BACKGROUND: Flying foxes (megachiroptera) and insectivorous microbats
      (microchiroptera) are the known reservoirs for a range of recently emerged,
      highly pathogenic viruses. In Australia there is public health concern relating
      to bats' role as reservoirs of Australian Bat Lyssavirus (ABLV), which has
      clinical features identical to classical rabies. Three deaths from ABLV have
      occurred in Australia. A survey was conducted to determine the frequency of bat
      exposures amongst adults in Australia's most populous state, New South Wales;
      explore reasons for handling bats; examine reported practices upon encountering
      injured or trapped bats or experiencing bat bites or scratches; and investigate
      knowledge of bat handling warnings. METHODS: A representative sample of 821 New
      South Wales adults aged 16 years and older were interviewed during May and June
      2011, using a computer assisted telephone interview (CATI) method. Frequencies,
      proportions and statistical differences in proportion were performed. Using an
      alpha-value of 0.05 and power of 80%, it was calculated that a sample size of 800
      was required to provide statistical significance of +/- 5% for dichotomous
      variables. RESULTS: One-hundred-and-twenty-seven (15.5%) respondents indicated
      that they had previously handled a bat, being 22% (48/218) rural and 13% (78/597)
      urban respondents (chi2 = 9.8, p = 0.0018). Twenty one percent of males (63/304)
      had handled bats compared with 12% (64/517) of females (chi2 = 10.2, p = 0.0014).
      Overall, 42.0% (n = 345) of respondents reported having seen or heard a warning
      about handling bats. If faced with an injured or trapped bat, 25% (206/821)
      indicated that they would handle the bat, with 17% (36/206) saying that they
      would use their bare hands. For minor scratches, 14% (117/821) indicated that
      they would ignore the injury while four respondents would ignore major scratches
      or bites. CONCLUSIONS: Previous human-bat interactions were relatively common.
      Bat exposures most frequently occurred with sick or injured bats, which have the
      highest risk of ABLV. On encountering an injured or sick bat, potentially high
      risk practices were commonly reported, particularly among rural males. It is
      important to understand why people still handle bats despite public health
      warnings to inform future communication strategies.

PMID- 24443961
TI  - An integrated genetic map based on four mapping populations and quantitative
      trait loci associated with economically important traits in watermelon (Citrullus
      lanatus).
AB  - BACKGROUND: Modern watermelon (Citrullus lanatus L.) cultivars share a narrow
      genetic base due to many years of selection for desirable horticultural
      qualities. Wild subspecies within C. lanatus are important potential sources of
      novel alleles for watermelon breeding, but successful trait introgression into
      elite cultivars has had limited success. The application of marker assisted
      selection (MAS) in watermelon is yet to be realized, mainly due to the past lack
      of high quality genetic maps. Recently, a number of useful maps have become
      available, however these maps have few common markers, and were constructed using
      different marker sets, thus, making integration and comparative analysis among
      maps difficult. The objective of this research was to use single-nucleotide
      polymorphism (SNP) anchor markers to construct an integrated genetic map for C.
      lanatus. RESULTS: Under the framework of the high density genetic map, an
      integrated genetic map was constructed by merging data from four independent
      mapping experiments using a genetically diverse array of parental lines, which
      included three subspecies of watermelon. The 698 simple sequence repeat (SSR),
      219 insertion-deletion (InDel), 36 structure variation (SV) and 386 SNP markers
      from the four maps were used to construct an integrated map. This integrated map
      contained 1339 markers, spanning 798 cM with an average marker interval of 0.6
      cM. Fifty-eight previously reported quantitative trait loci (QTL) for 12 traits
      in these populations were also integrated into the map. In addition, new QTL
      identified for brix, fructose, glucose and sucrose were added. Some QTL
      associated with economically important traits detected in different genetic
      backgrounds mapped to similar genomic regions of the integrated map, suggesting
      that such QTL are responsible for the phenotypic variability observed in a broad
      array of watermelon germplasm. CONCLUSIONS: The integrated map described herein
      enhances the utility of genomic tools over previous watermelon genetic maps. A
      large proportion of the markers in the integrated map are SSRs, InDels and SNPs,
      which are easily transferable across laboratories. Moreover, the populations used
      to construct the integrated map include all three watermelon subspecies, making
      this integrated map useful for the selection of breeding traits, identification
      of QTL, MAS, analysis of germplasm and commercial hybrid seed detection.

PMID- 24443962
TI  - Gender-specificity of solitary and dyadic sexual desire among gynephilic and
      androphilic women and men.
AB  - INTRODUCTION: Incentive motivation theory proposes that sexual desire emerges
      from sexual arousal, and is triggered by sexually competent stimuli. Research
      demonstrates gender and sexual orientation differences in the features that
      contribute to the competency of sexual stimuli. Men's and gynephilic women's
      genital arousal tends to be gender-specific with preferred gender eliciting
      significantly greater genital arousal than nonpreferred gender. In contrast,
      stimuli depicting preferred and nonpreferred gender elicit similar degrees of
      genital arousal among androphilic women, termed a gender-nonspecific pattern.
      Given these differences in the features that elicit a sexual response, and that
      sexual desire is proposed to emerge from sexual arousal, the question remains as
      to whether sexual desire would emerge only through exposure to preferred stimuli
      or whether patterns of responsive desire would parallel those observed for
      genital arousal. AIM: The study aims to examine patterns of dyadic and solitary
      sexual desire in response to stimuli differing in incentive value. METHODS:
      Thirty androphilic women, 21 gynephilic women, 21 gynephilic men, and 16
      androphilic men participated in a sexual psychophysiological session.
      Participants viewed sexual stimuli that varied the gender of the actors and the
      intensity of sexual activities depicted. MAIN OUTCOME MEASURES: Participants
      reported their degree of desire for sex with a partner (dyadic desire) and desire
      to masturbate (solitary desire), before and after each film. RESULTS: Men and
      gynephilic women exhibited gender-specific patterns of sexual desire. Androphilic
      women's dyadic desire showed significantly less differentiation between genders,
      and their solitary desire did not differentiate at all. No gender difference was
      observed for either type of desire. All groups reported greater desire as
      stimulus intensity increased. CONCLUSIONS: Gender-nonspecific sexual response is
      not limited to the sexual arousal patterns of androphilic women, but extends to
      include responsive sexual desire. Men and gynephilic women, however, show gender
      specific responsive sexual desire that parallels their sexual arousal patterns.

PMID- 24443964
TI  - Review: The genetics of Alzheimer's disease; putting flesh on the bones.
AB  - For two decades the search for genes involved in Alzheimer's disease brought
      little reward; it was not until the advent of genome-wide association studies
      (GWAS) that genetic associations started to be revealed. Since 2009 increasingly
      large GWAS have revealed 20 loci, which in itself is a substantial increase in
      our understanding, but perhaps the more important feature is that these studies
      have highlighted novel pathways that are potentially involved in the disease
      process. This commentary assembles our latest knowledge while acknowledging that
      the casual functional variants, and undoubtedly, other genes are still yet to be
      discovered. This is the challenge that remains and the promise of next-generation
      sequencing is anticipated as there are a number of large initiatives which
      themselves should start to yield information before long. 

PMID- 24443965
TI  - Mindfulness-based relationship education for couples expecting their first child
      part 2: phenomenological findings.
AB  - This phenomenological study is the second phase of a larger mixed methods study
      of a relationship-enhancement program for couples expecting their first child
      (see Gambrel & Piercy, this issue). The 4-week Mindful Transition to Parenthood
      Program uses mindfulness practices and interpersonal activities to develop skills
      of internal and interpersonal attunement. Based on semi-structured interviews
      with thirteen couples, four overarching themes emerged: (a) positive changes for
      self, (b) improvements in couple relationship, (c) more prepared for baby, and
      (d) male involvement. Participants stated that the program increased their
      acceptance and awareness, deepened connections with their partners, and led them
      to be more confident about becoming parents. Male participants felt they became
      more identified as fathers. The authors discuss the clinical implications of
      these findings. 

PMID- 24443966
TI  - A question of persistence: Langerhans cells and graft-versus-host disease.
AB  - Langerhans cells (LCs) have been scrutinized many times in studies of the
      pathogenesis of graft-versus-host disease (GVHD). As migratory dendritic cells,
      LCs are capable of direct antigen presentation to cytotoxic T cells. Their self
      renewal capacity has led to speculation that persistent recipient LCs could
      provide a continuous source of host antigen to donor T cells infused during
      hematopoietic stem cell transplantation (HSCT). In this issue of Experimental
      Dermatology, a new study examines at the relationship between recipient LCs and
      chronic GVHD. 

PMID- 24443967
TI  - Seasonal variations of antimicrobial activity and chemical composition of
      essential oils extracted from three Citrus limon L. Burm. cultivars.
AB  - In order to investigate the seasonal variations of antimicrobial properties and
      chemical composition of essential oils (EOs), three different cultivars of Citrus
      limon L. Burm. spp. (Femminello Santa Teresa, Monachello and Femminello
      Continella) were collected at 6-week intervals, from December 2012 to April 2013,
      for a total of four harvests. The EOs were extracted from lemon peel by hydro
      distillation. The antimicrobial activity, tested by paper disc diffusion method,
      was evaluated against common food-related pathogenic bacteria (Listeria
      monocytogenes, Staphylococcus aureus, Salmonella enterica and Enterobacter spp.).
      EOs were more effective against Gram-positive than Gram-negative bacteria at each
      collection time, but a strong strain dependence was evidenced. Monachello EOs
      showed the highest inhibition power. The chemical characterisation of the EOs
      performed by gas chromatography/mass spectrometry identified from 36 to 42
      molecules. The chemical difference registered among samples and seasons may
      explain the different antimicrobial efficacies recorded. 

PMID- 24443968
TI  - Nonlinear effects of temperature on body form and developmental canalization in
      the threespine stickleback.
AB  - Theoretical models predict that nonlinear environmental effects on the phenotype
      also affect developmental canalization, which in turn can influence the tempo and
      course of organismal evolution. Here, we used an oceanic population of threespine
      stickleback (Gasterosteus aculeatus) to investigate temperature-induced
      phenotypic plasticity of body size and shape using a paternal half-sibling, split
      clutch experimental design and rearing offspring under three different
      temperature regimes (13, 17 and 21  degrees C). Body size and shape of 466
      stickleback individuals were assessed by a set of 53 landmarks and analysed using
      geometric morphometric methods. At approximately 100 days, individuals differed
      significantly in both size and shape across the temperature groups. However, the
      temperature-induced differences between 13 and 17  degrees C (mainly comprising
      relative head and eye size) deviated considerably from those between 17 and 21 
      degrees C (involving the relative size of the ectocoracoid, the operculum and the
      ventral process of the pelvic girdle). Body size was largest at 17  degrees C.
      For both size and shape, phenotypic variance was significantly smaller at 17 
      degrees C than at 13 and 21  degrees C, indicating that development is most
      stable at the intermediate temperature matching the conditions encountered in the
      wild. Higher additive genetic variance at 13 and 21  degrees C indicates that the
      plastic response to temperature had a heritable basis. Understanding nonlinear
      effects of temperature on development and the underlying genetics are important
      for modelling evolution and for predicting outcomes of global warming, which can
      lead not only to shifts in average morphology but also to destabilization of
      development.

PMID- 24443969
TI  - Novel anticancer strategy aimed at targeting shelterin complexes by the induction
      of structural changes in telomeric DNA: hitting two birds with one stone.
AB  - The ends of chromosomes in mammals are composed of telomeric DNA containing
      TTAGGG repeats, which bind specific proteins called shelterins. This telomeric
      DNA together with shelterins form a cap that protects the ends of chromosomes
      from being recognized as sites of DNA damage and from chromosomal fusions. Many
      very successful antitumor drugs used in the treatment of cancer patients bind to
      DNA, some of them with a prominent sequence specificity leads to changes in DNA
      structure and integrity. We propose a new target for antitumor drugs where small
      molecule ligands can bind to telomeric DNA and induce specific structural
      changes. These changes would lead to a selective interference with the formation
      of telomeric DNA-shelterin complexes, especially involving TRF1 and TRF2
      proteins, as these proteins bind double-stranded telomeric DNA in a sequence- and
      structure-dependent manner. The rationale of the proposed therapeutic strategy is
      further justified by the fact that tumor cells have relatively short telomeres
      and frequently de-regulated shelterin expression and/or functionality. Thus
      uncapping of chromosome ends by DNA binding compounds which disrupt DNA-shelterin
      complexes can ultimately induce selective cytotoxic effect in tumor cells.
      Possible implications for rational design of new antitumor drugs which interfere
      with telomeric DNA structure and formation of DNA-shelterin complexes are
      discussed. 

PMID- 24443970
TI  - Maternal and newborn outcomes among women with schizophrenia: a retrospective
      population-based cohort study.
AB  - OBJECTIVE: More women with schizophrenia are becoming pregnant, such that
      contemporary data are needed about maternal and newborn outcomes in this
      potentially vulnerable group. We aimed to quantify maternal and newborn health
      outcomes among women with schizophrenia. DESIGN: Retrospective cohort study.
      SETTING: Population based in Ontario, Canada, from 2002 to 2011. POPULATION:
      Ontario women aged 15-49 years who gave birth to a liveborn or stillborn
      singleton infant. METHODS: Women with schizophrenia (n = 1391) were identified
      based on either an inpatient diagnosis or two or more outpatient physician
      service claims for schizophrenia within 5 years prior to conception. The
      reference group comprised 432 358 women without diagnosed mental illness within
      the 5 years preceding conception in the index pregnancy. MAIN OUTCOME MEASURES:
      The primary maternal outcomes were gestational diabetes mellitus, gestational
      hypertension, pre-eclampsia/eclampsia, and venous thromboembolism. The primary
      neonatal outcomes were preterm birth, and small and large birthweight for
      gestational age (SGA and LGA). Secondary outcomes included additional key
      perinatal health indicators. RESULTS: Schizophrenia was associated with a higher
      risk of pre-eclampsia (adjusted odds ratio, aOR 1.84; 95% confidence interval,
      95% CI 1.28-2.66), venous thromboembolism (aOR 1.72, 95% CI 1.04-2.85), preterm
      birth (aOR 1.75, 95% CI 1.46-2.08), SGA (aOR 1.49, 95% CI 1.19-1.86), and LGA
      (aOR 1.53, 95% CI 1.17-1.99). Women with schizophrenia also required more
      intensive hospital resources, including operative delivery and admission to a
      maternal intensive care unit, paralleled by higher neonatal morbidity.
      CONCLUSIONS: Women with schizophrenia are at higher risk of multiple adverse
      pregnancy outcomes, paralleled by higher neonatal morbidity. Attention should
      focus on interventions to reduce the identified health disparities.

PMID- 24443971
TI  - Role of tRNA orthogonality in an expanded genetic code.

PMID- 24443972
TI  - Delivery of negatively charged liposomes into the atherosclerotic plaque of
      apolipoprotein E-deficient mouse aortic tissue.
AB  - Liposomes have been used to diagnose and treat cancer and, to a lesser extent,
      cardiovascular disease. We previously showed the uptake of anionic liposomes into
      the atheromas of Watanabe heritable hyperlipidemic rabbits within lipid pools.
      However, the cellular distribution of anionic liposomes in atherosclerotic plaque
      remains undescribed. In addition, how anionic liposomes are absorbed into
      atherosclerotic plaque is unclear. We investigated the uptake and distribution of
      anionic liposomes in atherosclerotic plaque in aortic tissues from apolipoprotein
      E-deficient (ApoE(-/-)) mice. To facilitate the tracking of liposomes, we used
      liposomes containing fluorescently labeled non-silencing small interfering RNA.
      Confocal microscopy analysis showed the uptake of anionic liposomes into
      atherosclerotic plaque and colocalization with macrophages. Transmission electron
      microscopy analysis revealed anionic liposomal accumulation in macrophages. To
      investigate how anionic liposomes cross the local endothelial barrier, we
      examined the role of clathrin-mediated endocytosis in human coronary artery
      endothelial cells (HCAECs) treated with or without the inflammatory cytokine
      tumor necrosis factor (TNF)-alpha. Pretreatment with amantadine, an inhibitor of
      clathrin-mediated endocytosis, significantly decreased liposomal uptake in HCAECs
      treated with or without TNF-alpha by 77% and 46%, respectively. Immunoblot
      analysis showed that endogenous clathrin expression was significantly increased
      in HCAECs stimulated with TNF-alpha but was inhibited by amantadine. These
      studies indicated that clathrin-mediated endocytosis is partly responsible for
      the uptake of liposomes by endothelial cells. Our results suggest that anionic
      liposomes target macrophage-rich areas of vulnerable plaque in ApoE(-)(/)(-)
      mice; this finding may lead to the development of novel diagnostic and
      therapeutic strategies for treating vulnerable plaque in humans.

PMID- 24443973
TI  - L-Arabinose isomerase and D-xylose isomerase from Lactobacillus reuteri:
      characterization, coexpression in the food grade host Lactobacillus plantarum,
      and application in the conversion of D-galactose and D-glucose.
AB  - The L-arabinose isomerase (L-AI) and the D-xylose isomerase (D-XI) encoding genes
      from Lactobacillus reuteri (DSMZ 17509) were cloned and overexpressed in
      Escherichia coli BL21 (DE3). The proteins were purified to homogeneity by one
      step affinity chromatography and characterized biochemically. L-AI displayed
      maximum activity at 65  degrees C and pH 6.0, whereas D-XI showed maximum
      activity at 65  degrees C and pH 5.0. Both enzymes require divalent metal ions.
      The genes were also ligated into the inducible lactobacillal expression vectors
      pSIP409 and pSIP609, the latter containing a food grade auxotrophy marker instead
      of an antibiotic resistance marker, and the L-AI- and D-XI-encoding
      sequences/genes were coexpressed in the food grade host Lactobacillus plantarum .
      The recombinant enzymes were tested for applications in carbohydrate conversion
      reactions of industrial relevance. The purified L-AI converted D-galactose to D
      tagatose with a maximum conversion rate of 35%, and the D-XI isomerized D-glucose
      to D-fructose with a maximum conversion rate of 48% at 60  degrees C.

PMID- 24443974
TI  - Epigenetic marking of sperm by post-translational modification of histones and
      protamines.
AB  - BACKGROUND: The concept that individual traits can be acquired and transmitted by
      the germline through epigenetic mechanisms has gained recognition in the past
      years. However, epigenetic marks in sperm have not been are not well identified.
      RESULTS: Using a novel proteomic approach that combines peptide-based bottom-up
      and intact protein top-down tandem mass spectrometry, we report the
      identification of epigenetic marks on histones and protamines in adult mouse
      sperm. We identified a total of 26 post-translational modifications (PTMs) on
      specific residues of the core histones H2B, H3 and H4, and the linker histone H1,
      four of which had not been described previously in any tissue or cell line. We
      also detected 11 novel PTMs on the protamines PRM1 and PRM2 and observed that
      they are present in specific combinations on individual protamines. CONCLUSIONS:
      Both histones and protamines carry multiple PTMs in the adult mouse sperm. On
      protamines, specific PTM combinations might form a 'protamine code' similar to
      the 'histone code'. These findings suggest a potential role for PTMs on sperm
      histones and protamines in epigenetic signatures underlying transgenerational
      inheritance.

PMID- 24443975
TI  - Development and validation of the Greek severe impairment battery (SIB).
AB  - BACKGROUND: Most neuropsychological batteries, especially those most often used,
      are unsuitable for the assessment of patients with severe dementia. The Severe
      Impairment Battery (SIB) was developed for the evaluation of preserved cognitive
      functions in these patients. The aim of this study was to formulate a Greek
      version of the SIB and to conduct a first assessment of its use of patients with
      mild, moderate, or severe Alzheimer's disease (AD), compared to the Mini-Mental
      State Examination (MMSE). METHODS: A convenience sample of 42 dementia patients
      according to DSM-IV-TR criteria and 23 healthy participants was selected.
      Patients were assessed twice using a Greek translation of the SIB and the Greek
      version of MMSE. Patients were divided into three severity groups based on
      grouped by Clinical Dementia Rating (CDR) score and the SIB and MMSE scores were
      compared. RESULTS: The validity of the SIB was confirmed by evaluating the
      correlation coefficients between the SIB and Greek-MMSE, grouped by CDR, which
      were found to be significant. Cronbach's alpha for the total SIB score and each
      subscale score showed high significance, and the item-total correlation for each
      subscale was also acceptable. The test-retest correlation for the total SIB score
      and subscale scores were significant. The total SIB score and subscale scores
      were examined according to CDR. CONCLUSION: The Greek SIB is reliable and valid
      in differentiating patients with moderate or severe dementia, whereas MMSE loses
      sensitivity due to a floor and ceiling effect.

PMID- 24443976
TI  - "Three-unit" muscle reconstruction in secondary cleft lip repair.
AB  - Background :  Secondary deformities are common in people born with unilateral
      cleft lip and palate. In recent years, more and more attempts and efforts have
      been directed toward muscle reconstruction. The authors present a new method of
      orbicularis oris repair in correction of secondary cleft lip deformities. Methods
      :  From April 2009 to April 2013, a total of 28 patients underwent this procedure
      in the authors' department and had a follow-up with a minimum length of 1 year.
      Muscle reconstruction was divided into three units that deal with the nasal
      floor, white lip, and red lip. Common anatomical pathologies including a deviated
      columella, blunted alar-facial groove, lack of philtral column, "free border"
      deficiency, and unapparent vermilion tubercle can be corrected in a single
      operation. Results :  The average follow-up period was 14.6 months (range, 12 to
      24 months). Contractubex gel (Merz Pharma, Frankfurt, Germany) was used to treat
      prominent or reddish scars in 16 patients. No major complications occurred. All
      the patients were satisfied with their nasolabial appearance. Conclusions : 
      "Three-unit" muscle repair was found to be effective and practical in secondary
      repair. Improved aesthetic and functional results can be achieved with this
      comprehensive procedure. 

PMID- 24443977
TI  - Modification of the dingman mouth gag for better visibility and access in the
      management of cleft palate.
AB  - Palatal and pharyngeal surgeries often require wide visibility and access.
      Various mouth gags and retractors have been devised and many modifications
      suggested to optimize these surgeries. The Dingman mouth gag, one of the commonly
      used retractors, offers a lot of advantages in terms of good mouth opening,
      tongue retraction, self-retaining cheek retractors, and anchorage for sutures,
      but it has a main limitation in that it allows only limited visibility of the
      anterior palate and alveolus. Hence, a modification of the Dingman mouth gag is
      presented for better visibility of and accessibility to the anterior palate. 

PMID- 24443978
TI  - Scaling up family medicine training in Gezira, Sudan - a 2-year in-service master
      programme using modern information and communication technology: a survey study.
AB  - BACKGROUND: In 2010 the Gezira Family Medicine Project (GFMP) was initiated in
      Gezira state, Sudan, designed as an in-service training model. The project is a
      collaboration project between the University of Gezira, which aims to provide a 2
      year master's programme in family medicine for practicing doctors, and the
      Ministry of Health, which facilitates service provision and funds the training
      programme. This paper presents the programme, the teaching environment, and the
      first batch of candidates enrolled. METHODS: In this study a self-administered
      questionnaire was used to collect baseline data at the start of the project from
      doctors who joined the programme. A checklist was also used to assess the health
      centres where they work. A total of 188 out of 207 doctors responded (91%), while
      data were gathered from all 158 health centres (100%) staffed by the programme
      candidates. RESULTS: The Gezira model of in-service family medicine training has
      succeeded in recruiting 207 candidates in its first batch, providing health
      services in 158 centres, of which 84 had never been served by a doctor before.
      The curriculum is community oriented. The mean age of doctors was 32.5 years, 57%
      were males, and 32% were graduates from the University of Gezira. Respondents
      stated high confidence in practicing some skills such as asthma management and
      post-abortion uterine evacuation. They were least confident in other skills such
      as managing depression or inserting an intrauterine device. The majority of
      health centres was poorly equipped for management of noncommunicable diseases, as
      only 10% had an electrocardiography machine (ECG), 5% had spirometer, and 1% had
      a defibrillator. CONCLUSIONS: The Gezira model has responded to local health
      system needs. Use of modern information and communication technology is used to
      facilitate both health service provision and training. The GFMP represents an
      example of a large-volume scaling-up programme of family medicine in Africa.

PMID- 24443979
TI  - Drought enhances folivory by shifting foliar metabolomes in Quercus ilex trees.
AB  - At the molecular level, folivory activity on plants has mainly been related to
      the foliar concentrations of nitrogen (N) and/or particular metabolites. We
      studied the responses of different nutrients and the whole metabolome of Quercus
      ilex to seasonal changes and to moderate field experimental conditions of
      drought, and how this drought may affect folivory activity, using stoichiometric
      and metabolomic techniques. Foliar potassium (K) concentrations increased in
      summer and consequently led to higher foliar K : phosphorus (P) and lower carbon
      (C) : K and N : K ratios. Foliar N : P ratios were not lowest in spring as
      expected by the growth rate hypothesis. Trees exposed to moderate drought
      presented higher concentrations of total sugars and phenolics and these trees
      also experienced more severe folivory attack. The foliar increases in K, sugars
      and antioxidant concentrations in summer, the driest Mediterranean season,
      indicated enhanced osmoprotection under natural drought conditions. Trees under
      moderate drought also presented higher concentrations of sugars and phenolics; a
      plant response to avoid water loss. These shifts in metabolism produced an
      indirect relationship between increased drought and folivory activity.

PMID- 24443980
TI  - Dry eye management in a Sjogren's syndrome mouse model by inhibition of p38-MAPK
      pathway.
AB  - BACKGROUND: To investigate the therapeutic effect of p38-MAPK inhibitor,
      SB203580, on dry eye in a mouse model of Sjogren's syndrome (MRL/lpr mice).
      METHODS: 18 female BALB/c mice and 44 female MRL/lpr mice were included. Mice
      were randomly assigned to the control or treatment group. The expression of
      phospho-p38 MAPK in lacrimal glands of BALB/c mice was determined by Western blot
      analysis following IL-1beta treatment at various time points. Different doses of
      SB203580 were injected into lacrimal glands of MRL/lpr mice and phenol red thread
      test was performed seven days post-injection. Moreover, the levels of
      acetylcholine and norepinephrine expression in lacrimal glands of MRL/lpr mice
      were measured using spectrofluoremetric assay and the histopathology of lacrimal
      glands was also evaluated. RESULTS: The expression of p-p38 MAPK in lacrimal
      glands of BALB/c mice gradually increased following incubation with IL-1beta ex
      vivo. Injection of SB203580 into lacrimal glands significantly improved the
      results of phenol red thread test in MRL/lpr mice. In addition, the secretions of
      acetylcholine and norepinephrine increased significantly compared to the control
      group. Less lymphocytes infiltration was observed in pathological section of
      lacrimal glands following SB203580 injection. CONCLUSIONS: Our results indicate
      that the activation of p38-MAPK pathway plays an important role in dry eye of a
      Sjogren's syndrome mouse model. Inhibition of p38-MAPK pathway by SB203580 might
      have potential therapeutic effect on Sjogren's syndrome associated dry eye.
      VIRTUAL SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1256849631103092.

PMID- 24443982
TI  - Study protocol: non-displaced distal radial fractures in adult patients: three
      weeks vs. five weeks of cast immobilization: a randomized trial.
AB  - BACKGROUND: Up to 30% of patients suffer from long-term functional restrictions
      following conservative treatment of distal radius fractures. Whether duration of
      cast immobilisation influences functional outcome remains unclear.
      METHODS/DESIGN: The aim of the study is to evaluate whether the duration of
      immobilization of non or minimally displaced distal radial fractures can be
      safely reduced. We will compare three weeks of plaster cast immobilization with
      five weeks of plaster cast immobilization in adult patient with non or minimally
      displaced distal radial fractures. STUDY DESIGN: a prospective randomized
      clinical trial. STUDY POPULATION: adult (>18 years) (independent in activities of
      daily living) patients with a non/minimal displaced distal radius fracture
      (dorsal angulation <15 degrees , volar tilt <20 degrees , radial inclination >15
      degrees , ulnar positive variance <5 mm and an articular step off <2 mm).
      INTERVENTION: three weeks of plaster cast immobilization versus five weeks of
      plaster cast immobilization.Main study parameters: primary outcome parameters:
      Patient related wrist evaluation (PRWE) Quick Disability of Arm, Shoulder and
      Hand (QUICKDASH) score after a one year follow-up, and secondary parameters:
      range of motion, pain level (VAS) and complications. DISCUSSION: The expectation
      of this study is that shorter duration of plaster cast immobilisation is
      beneficial for the patient with a distal radius fracture. This risk of specific
      complications is low and generally similar in both treatment options. Moreover,
      the burden of the study is not much higher compared to standard treatment. Follow
      up is standardized according to current trauma guidelines. Literature indicates
      that both treatment options from the study are accepted for displaced distal
      radius fractures. No clear advantage for one treatment options is found at
      present in the literature, although there is no level I evidence present. This
      trial will provide level-1 evidence for the comparison of consolidation and
      functional outcome between two treatment options for non-displaced distal radial
      fractures. The gathered data may support the development of a clinical guideline
      for conservative treatment of distal radial fractures. TRIAL REGISTRATION:
      Netherlands National Trial Register NTR3552.

PMID- 24443981
TI  - Brain cell swelling during hypocapnia increases with hyperglycemia or ketosis.
AB  - BACKGROUND: Severe hypocapnia reduces cerebral blood flow (CBF) and is known to
      be a risk factor for diabetic ketoacidosis (DKA)-related cerebral edema and
      cerebral injury in children. Reductions in CBF resulting from hypocapnia alone,
      however, would not be expected to cause substantial cerebral injury. We
      hypothesized that either hyperglycemia or ketosis might alter the effects of
      hypocapnia on CBF and/or cerebral edema associated with CBF reduction. METHODS:
      We induced hypocapnia (pCO2 20 +/- 3 mmHg) via mechanical ventilation in three
      groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451 +/
      78 mg/dL), and 15 ketotic rats (beta-hydroxy butyrate 3.0 +/- 1.0 mmol/L). We
      used magnetic resonance imaging to measure CBF and apparent diffusion coefficient
      (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40 +/- 3
      mmHg). In a subset (n = 35), after 2 h of hypocapnia, pCO2 levels were normalized
      (40 +/- 3 mmHg) and ADC and CBF measurements were repeated. RESULTS: Declines in
      CBF with hypocapnia occurred in all groups. Normalization of pCO2 after
      hypocapnia resulted in hyperemia in the striatum. These effects were not
      substantially altered by hyperglycemia or ketosis. Declines in ADC (suggesting
      brain cell swelling) during hypocapnia, however, were greater during both
      hyperglycemia and ketosis. CONCLUSIONS: We conclude that brain cell swelling
      associated with hypocapnia is increased by both hyperglycemia and ketosis,
      suggesting that these metabolic conditions may make the brain more vulnerable to
      injury during hypocapnia.

PMID- 24443983
TI  - Metal-core/semiconductor-shell nanocones for broadband solar absorption
      enhancement.
AB  - Nanostructure-based photovoltaic devices have exhibited several advantages, such
      as reduced reflection, extraordinary light trapping, and so forth. In particular,
      semiconductor nanostructures provide optical modes that have strong dependence on
      the size and geometry. Metallic nanostructures also attract a lot of attention
      because of the appealing plasmonic effect on the near-field enhancement. In this
      study, we propose a novel design, the metal-core/semiconductor-shell nanocones
      with the core radius varying in a linearly gradient style. With a thin layer of
      semiconductor absorber coated on a metallic cone, such a design can lead to
      significant and broadband absorption enhancement across the entire visible and
      near-infrared solar spectrum. As an example of demonstration, a layer of 16 nm
      thick crystalline silicon (c-Si) coated on a silver nanocone can absorb 27% of
      standard solar radiation across a broad spectral range of 300-1100 nm, which is
      equivalent to a 700 nm thick flat c-Si film. Therefore, the absorption
      enhancement factor approaching the Yablonovitch limit is achieved with this
      design. The significant absorption enhancement can be ascribed to three types of
      optical modes, that is, Fabry-Perot modes, plasmonic modes, and hybrid modes that
      combine the features of the previous two. In addition, the unique nanocone
      geometry enables the linearly gradient radius of the semiconductor shell, which
      can support multiple optical resonances, critical for the broadband absorption.
      Our design may find general usage as elements for the low cost, high efficiency
      solar conversion and water-splitting devices. 

PMID- 24443984
TI  - Projected effects of climate and development on California wildfire emissions
      through 2100.
AB  - Changing climatic conditions are influencing large wildfire frequency, a globally
      widespread disturbance that affects both human and natural systems. Understanding
      how climate change, population growth, and development patterns will affect the
      area burned by and emissions from wildfires and how populations will in turn be
      exposed to emissions is critical for climate change adaptation and mitigation
      planning. We quantified the effects of a range of population growth and
      development patterns in California on emission projections from large wildfires
      under six future climate scenarios. Here we show that end-of-century wildfire
      emissions are projected to increase by 19-101% (median increase 56%) above the
      baseline period (1961-1990) in California for a medium-high temperature scenario,
      with the largest emissions increases concentrated in northern California. In
      contrast to other measures of wildfire impacts previously studied (e.g.,
      structural loss), projected population growth and development patterns are
      unlikely to substantially influence the amount of projected statewide wildfire
      emissions. However, increases in wildfire emissions due to climate change may
      have detrimental impacts on air quality and, combined with a growing population,
      may result in increased population exposure to unhealthy air pollutants. 

PMID- 24443985
TI  - More evidence of the problems of using HbA1c for diagnosing diabetes? The known
      knowns, the known unknowns and the unknown unknowns.

PMID- 24443986
TI  - Exploring mechanisms linked to differentiation and function of dimorphic
      chloroplasts in the single cell C4 species Bienertia sinuspersici.
AB  - BACKGROUND: In the model single-cell C4 plant Bienertia sinuspersici, chloroplast
      and nuclear-encoded photosynthetic enzymes, characteristically confined to
      either bundle sheath or mesophyll cells in Kranz-type C4 leaves, all occur
      together within individual leaf chlorenchyma cells. Intracellular separation of
      dimorphic chloroplasts and key enzymes within central and peripheral compartments
      allow for C4 carbon fixation analogous to NAD-malic enzyme (NAD-ME) Kranz type
      species. Several methods were used to investigate dimorphic chloroplast
      differentiation in B. sinuspersici. RESULTS: Confocal analysis revealed that
      Rubisco-containing chloroplasts in the central compartment chloroplasts (CCC)
      contained more photosystem II proteins than the peripheral compartment
      chloroplasts (PCC) which contain pyruvate,Pi dikinase (PPDK), a pattern analogous
      to the cell type-specific chloroplasts of many Kranz type NAD-ME species.
      Transient expression analysis using GFP fusion constructs containing various
      lengths of a B. sinuspersici Rubisco small subunit (RbcS) gene and the transit
      peptide of PPDK revealed that their import was not specific to either chloroplast
      type. Immunolocalization showed the rbcL-specific mRNA binding protein RLSB to be
      selectively localized to the CCC in B. sinuspersici, and to Rubisco-containing BS
      chloroplasts in the closely related Kranz species Suaeda taxifolia. Comparative
      fluorescence analyses were made using redox-sensitive and insensitive GFP forms,
      as well comparative staining using the peroxidase indicator 3,3-diaminobenzidine
      (DAB), which demonstrated differences in stromal redox potential, with the CCC
      having a more negative potential than the PCC. CONCLUSIONS: Both CCC RLSB
      localization and the differential chloroplast redox state are suggested to have a
      role in post-transcriptional rbcL expression.

PMID- 24443987
TI  - Effect of citral and carvacrol on the susceptibility of Listeria monocytogenes
      and Listeria innocua to antibiotics.
AB  - The aim of this study was to evaluate the antibiotic susceptibility of Listeria
      innocua (L. innocua) and Listeria monocytogenes (L. monocytogenes) cells in the
      presence of citral and carvacrol at sublethal concentrations in an agar medium.
      The presence of terpenes in the L. monocytogenes and L. innocua culture medium
      provided a reduction in the minimal inhibitory concentration (MIC) of all the
      antibiotics tested. These effects were dependent on the concentration of terpenes
      present in the culture medium. The combination of citral and carvacrol
      potentiated antibiotic activity by reducing the MIC values of bacitracin and
      colistin from 32.0 and 128.0 MUg ml-1 to 1.0 and 2.0 MUg ml-1, respectively.
      Thus, both Listeria species became more susceptible to these drugs. In this way,
      the colistin and bacitracin resistance of L. monocytogenes and L. innocua was
      reversed in the presence of terpenes. Results obtained in this study show that
      the phytochemicals citral and carvacrol potentiate antibiotic activity, reducing
      the MIC values of cultured L. monocytogenes and L. innocua. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Phytochemicals citral and carvacrol potentiate antibiotic
      activity of erythromycin, bacitracin and colistin by reducing the MIC values of
      cultured Listeria monocytogenes and Listeria innocua. This effect in reducing the
      MIC values of the antibiotics tested in both micro-organisms was increased when
      natural antimicrobials were combined. This finding indicated that the combination
      among terpenes and antibiotic may contribute in reducing the required dosage of
      antibiotics due to the possible effect of terpenes on permeation barrier of the
      micro-organism cell membrane.

PMID- 24443988
TI  - Mitochondrial DNA copy number - but not a mitochondrial tandem CC to TT
      transition - is increased in sun-exposed skin.
AB  - Mitochondrial DNA (mtDNA) mutations are causatively associated with photo-ageing
      and are used as biomarkers of UV exposure. The most prominent mitochondrial
      mutation is the common deletion (CD), which is induced in many tissues by
      oxidative stress. More photo-specific mutations might be CC to TT tandem
      transitions which arise from UV-induced cyclobutane pyrimidine dimers. As
      nucleotide excision repair is absent in mitochondria, this DNA damage can
      presumably not be repaired resulting in high mitochondrial mutation levels. Here,
      we analysed levels of the CD, a mitochondrial and a chromosomal tandem transition
      in epidermis and dermis from exposed and less UV-exposed skin. We also analysed
      mtDNA copy number, for which changes as a result of oxidative stress have been
      described in different experimental settings. Whereas mitochondrial tandem
      transition levels were surprisingly low with no discernible correlation with UV
      exposure, mtDNA copy number and CD were significantly increased in UV-exposed
      samples. 

PMID- 24443989
TI  - Mate competition and resource competition are inter-related in sexual selection.
AB  - Sexual selection can be affected by the competition for limited breeding
      resources and/or the competition for limited mates. Although there is ample
      evidence for each type of competition by itself, little is known about their
      relative importance and interaction. To address these questions, we established
      48 experimental breeding populations of the two-spotted goby (Gobiusculus
      flavescens), a substrate-breeding fish with paternal care. In three experimental
      treatments, males were limited in the access to either nest sites or mates or
      were provided with both nests and mates in excess. We quantified male competition
      behaviour (agonistic and courtship), the opportunity for selection and selection
      on male body size. Limited access to nests and mates produced similar
      opportunities for selection, but only limited access to mates increased male
      competitive behaviours and caused positive selection on male body size. Selection
      on body size in the mate-limited treatment was due both to larger males being
      more likely to take up nests and to larger males being more likely to mate once
      they had a nest. These findings demonstrate that resource and mate limitation can
      differ in their effects on sexual selection. The results also reveal that
      resource and mating competition can be highly inter-related and not always
      separated in time, implying that methods to disentangle the two processes must be
      chosen with care. Future research should consider experimental and analytical
      approaches similar to those of the present study in attempts to elucidate the
      interaction of resource and mating competition in animals.

PMID- 24443990
TI  - Synthesis of ranolazine derivatives containing the (1S,4S)-2,5
      diazabicyclo[2.2.1]heptane moiety and their evaluation as vasodilating agents.
AB  - Two diazabicyclic analogues of ranolazine, (S,S,S)-5 and (S,S,R)-5, and their
      epimeric mixture were synthesized. Furthermore, their vasomotor effects on rat
      aorta rings precontracted with phenylephrine were analyzed. These compounds
      showed vasodilating effects significantly greater than ranolazine. The
      vasodilating activities of these analogues have two components, one that depends
      on the endothelium, due to the release of NO, and another one due to a direct
      effect on the vascular smooth muscle. The compounds [(S,S,S)(S,S,R)]-5 and
      (S,S,R)-5 induce, in a manner similar to ranolazine, the release of a prostanoid
      from the cyclooxygenase pathway, whose vasoconstrictor effect is masked by the
      predominant vasodilation induced by these compounds. 

PMID- 24443991
TI  - Determination of antiplasmodial activity and binding affinity of curcumin and
      demethoxycurcumin towards PfTrxR.
AB  - In our study, the inhibitory activity of curcuminoids towards Plasmodium
      falciparum thioredoxin reductase (PfTrxR) was determined using LC-MS-based
      functional assay and showed that only demethoxycurcumin (DMC) inhibited PfTrxR
      (IC50: 2 MUM). In silico molecular modelling was used to ascertain and further
      confirm that the binding affinities of curcumin and DMC are towards the dimer
      interface of PfTrxR. The in vitro antiplasmodial activities of curcumin and DMC
      were evaluated and shown to be active against chloroquine (CQ)-sensitive (D6
      clone) and moderately active against CQ-resistant (W2 clone) strains of
      Plasmodium falciparum while no cytotoxicity was observed against Vero cells.

PMID- 24443992
TI  - Imagery in mental contamination.
AB  - BACKGROUND: Intrusive imagery is experienced in a number of anxiety disorders,
      including Obsessive Compulsive Disorder (OCD). Imagery is particularly relevant
      to mental contamination, where unwanted intrusive images are hypothesized to
      evoke feelings of dirtiness and urges to wash (Rachman, 2006). AIMS: The aim of
      this study was to examine the nature of imagery associated with mental
      contamination. METHOD: Fifteen people with contaminated-based OCD completed a
      semi-structured imagery interview designed specifically for this study. RESULTS:
      Ten participants reported images associated with contamination. These images were
      vivid and distressing and evoked feelings of dirtiness. Participants engaged in a
      number of behaviours to neutralize their images, including compulsive washing. A
      small number of participants also reported images that protected them from
      contamination. CONCLUSIONS: In support of the theory of mental contamination
      (Rachman, 2006), images can lead to feelings of pollution and compulsive washing.
      Further research is needed to explore the role of imagery in maintaining
      contamination fears.

PMID- 24443993
TI  - TLR4 gene polymorphism in patients with nonalcoholic fatty liver disease in
      comparison to healthy controls.
AB  - OBJECTIVES: Recent studies have suggested that bacterial overgrowth and
      endotoxemia along with its receptor, Toll-like receptor 4 (TLR-4), play a role in
      the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The present study
      was designed to test and evaluate the TLR4 gene polymorphism in patients with
      NAFLD in comparison to healthy controls. METHODS: A total of 119 patients [mean
      (standard deviation, SD) age 43.4 (11.5) years, 55.5% were males] with NAFLD and
      80 healthy controls [mean (SD) age 40.9 (8.1) years, 67.5% were females)] were
      evaluated in terms of patient demographics, anthropometrics, blood biochemistry,
      liver histology, and ultrasonographic (USG) findings. Histological evaluation was
      performed in 111 patients, and blood samples were collected from 119 patients
      with NAFLD and 80 healthy persons. Allelic variants of TLR4 (Asp299Gly and
      Thr399Ile) were assayed by real-time PCR. Genomic DNA was amplified using FAM/VIC
      primers specific for allelic variants of TLR4 Asp299Gly and Thr399Ile with real
      time PCR. Amplicons were analyzed with high-resolution melting on a Light Cycler
      480 for detecting different melting patterns of polymorphic and wild-type
      alleles. RESULTS: The number of the subjects with heterozygous mutation at
      genotype 299 (Asp299Gly) was significantly lower in the NAFLD than in the control
      group (23.8 vs. 10.9%, P=0.027). Logistic regression analysis revealed that
      female gender [odds ratio (OR)=2.984, 95% confidence interval (CI) 1.561-5.360,
      P=0.001] and heterozygous (Asp299Gly) mutation at codon 299 (OR=2.998, 95% CI
      1.325-6.783, P=0.008) were the significant predictors of higher likelihood of
      TRL4 gene polymorphism-related prevention of NAFLD. CONCLUSIONS: As the first
      time-in-humans controlled study related to investigation of TLR4 gene
      polymorphism in NAFLD, our findings contribute to the available data that TLR-4
      signaling is pivotal for the pathogenesis of NASH and indicate that the TLR4
      codon 299 heterozygous gene mutation (Asp299Gly) in humans may have a preventive
      role against the genesis of NAFLD.

PMID- 24443994
TI  - Chemical composition, antioxidant and anti-AGEs activities of a French poplar
      type propolis.
AB  - Accumulation in tissues and serum of advanced glycation end-products (AGEs) plays
      an important role in pathologies such as Alzheimer's disease or, in the event of
      complications of diabetes, atherosclerosis or renal failure. Therefore, there is
      a potential therapeutic interest in compounds able to lower intra and
      extracellular levels of AGEs. Among them, natural antioxidants (AO) with true
      anti-AGEs capabilities would represent good candidates for development. The
      purpose of this study was to evaluate the AO and anti-AGEs potential of a
      propolis batch and then to identify the main compounds responsible for these
      effects. In vivo, protein glycation and oxidative stress are closely related.
      Thus, AO and antiglycation activities were evaluated using both DPPH and ORAC
      assays, respectively, as well as a newly developed automated anti-AGEs test.
      Several propolis extracts exhibited very good AO and anti-AGEs activities, and a
      bioguided fractionation allowed us to identify pinobanksin-3-acetate as the most
      active component. 

PMID- 24443995
TI  - Editorial.

PMID- 24443996
TI  - Low blood lead level effects on intelligence: can a dose-response curve be
      determined from the epidemiological data?
AB  - CONTEXT. Recent publications have graphically demonstrated a curvilinear
      relationship between measures of intelligence and blood lead levels at low
      concentrations (< 10 mcg/dl). This led to speculation that a greater biologic
      effect occurs at lower concentrations. Critics of this conclusion hypothesized
      that this graphical relationship may be a function of the underlying
      distributions of these variables. OBJECTIVE. To study the impact of the
      distribution of data on the shape of apparent dose-response curves. METHODS.
      Random data based on varied distributions were constructed to simulate a previous
      study using a single, randomly generated covariate income (Inc) to demonstrate
      the impact of normally versus exponentially distributed data on the shape of the
      graph of intelligence quotient (IQ) versus blood lead. We also used an existing
      database of US blood lead levels and constructed a similar model of income and IQ
      using both assumptions of distribution for the intermediate variable income.
      RESULTS. When both lead and income are exponentially distributed, the graph of
      lead and IQ will be a curve. CONCLUSION. The apparent shape of a dose-response
      relationship from simulated epidemiological data is nonlinear when one variable
      and a covariate are exponentially distributed. A non-linear biological
      relationship should not be assumed and in fact may be the least likely
      explanation. The use of observational epidemiological data to discern a dose
      response relationship between two variables may be misleading.

PMID- 24443997
TI  - The supralinear dose-response for environmental toxicants: a statistical
      artifact?

PMID- 24443998
TI  - Epigenetic mechanisms in the pathogenesis of Lynch syndrome.
AB  - Inherited defects in the DNA mismatch repair (MMR) system, MLH1, MSH2, MSH6, and
      PMS2 genes, underlie Lynch syndrome, one of the most prevalent cancer syndromes
      in man. The syndrome offers a model for cancers arising through MMR defects and
      microsatellite instability, which applies to ~ 15% of all colorectal,
      endometrial, and other cancers. Lynch syndrome also illustrates the significance
      of the epigenetic component in cancer development. Inactivation of tumor
      suppressor genes by epigenetic mechanisms is an acquired property of many tumors
      developing in Lynch syndrome. Furthermore, constitutional epimutations of MMR
      genes may explain a proportion of mutation-negative families lacking MLH1 or MSH2
      protein expression in tumor tissue. This review provides an update of the
      molecular basis of Lynch syndrome by focusing on the role of epigenetic
      mechanisms in the pathogenesis of the disease.

PMID- 24443999
TI  - A bibliometric analysis of toxicology research productivity in Middle Eastern
      Arab countries during a 10-year period (2003-2012).
AB  - BACKGROUND: Bibliometric studies are increasingly being used for research
      assessment by involving the application of statistical methods to scientific
      publications to obtain the bibliographics for each country. The main objective of
      this study was to analyse the research productivity originating from 13 Middle
      Eastern Arab (MEA) countries with articles published in toxicology journals.
      METHODS: Data from January 1, 2003 till December 31, 2012 were searched for
      documents with specific words in the toxicology field as a "source title" in any
      one of the 13 MEA countries. Research productivity was evaluated based on a
      methodology developed and used in other bibliometric studies. Research
      productivity was adjusted to the national population and nominal gross domestic
      product (GDP) per capita. RESULTS: Documents (n = 1,240) were retrieved from 73
      international peer-reviewed toxicology journals. The h-index of the retrieved
      documents was 39. Of the 73 journal titles, 52 (69.9%) have their IF listed in
      the ISI Journal Citation Reports 2012; 198 documents (16.0%) were published in
      journals that had no official IF. After adjusting for economy and population
      power, Egypt (193.6), Palestine (18.1), Kingdom of Saudi Arabia (KSA) (13.0), and
      Jordan (11.5) had the highest research productivity. Countries with large
      economies, such as the Kuwait, United Arab Emirates (UAE), and Oman, tended to
      rank relatively low after adjustment of GDP. The total number of citations at the
      time of data analysis (August 4, 2013) was 10,991, with a median (interquartile
      range) of 4 (1-11). MEA collaborated more with countries in the MEA regions
      (16.7%), especially KSA, Egypt, and UAE, followed by Europe (14.4%), especially
      with the United Kingdom and Germany. CONCLUSIONS: The present data show a
      promising rise and a good start for toxicology research activity in toxicology
      journals in the Arab world. Research output is low in some countries, which can
      be improved by investing in more international and national collaborative
      research projects in the field of toxicology.

PMID- 24444000
TI  - Locally existing endothelial cells and pericytes in ovarian stroma, but not bone
      marrow-derived vascular progenitor cells, play a central role in
      neovascularization during follicular development in mice.
AB  - BACKGROUND: Neovascularization is necessary for follicular growth.
      Vascularization is first observed in preantral follicles, and thereafter the
      vasculature markedly increases in follicles undergoing development.
      Neovascularization includes angiogenesis and vasculogenesis. Vasculogenesis is
      the formation of new blood vessels by bone marrow-derived endothelial progenitor
      cells. It is unclear whether vasculogenesis occurs during follicular growth.
      Blood vessels must be mature to be functional blood vessels. Mature blood vessels
      are characterized by the recruitment of pericytes. However, it is unclear where
      pericytes come from and whether they contribute to neovascularization in the
      follicle during follicular growth. In this study, we investigated whether bone
      marrow-derived progenitor cells that differentiate into vascular endothelial
      cells or pericytes contribute to neovascularization during follicular growth.
      METHODS: A parabiosis model was used in this study. Six-week-old wild-type and
      transgenic female mice expressing green fluorescent protein (GFP) were conjoined
      between the lateral abdominal regions to create a shared circulatory system.
      After 6 weeks, the ovaries were obtained and immunostained for CD31/CD34 (a
      vascular endothelial cell marker), platelet-derived growth factor receptor-beta
      (PDGFR-beta) (a pericyte marker), and GFP (a bone marrow-derived cell marker).
      RESULTS: Cells that were positive for CD34 and PDGFR-beta were observed in the
      stroma adjacent to the primary or early preantral follicles and in the theca cell
      layer of the follicles from the late preantral stage to the preovulatory stage.
      CD31/CD34 and GFP double-positive cells were observed in the theca cell layer of
      the follicle from the antral stage to the preovulatory stage while the number of
      double-positive cells in the preovulatory follicles did not increase. PDGFR-beta
      and GFP double-positive cells were observed in the theca cell layer of the
      preovulatory follicle but not in the smaller follicle. CONCLUSIONS: Locally
      existing endothelial cells and pericytes in the stroma play a central role in the
      neovascularization during follicular growth, while bone marrow-derived
      endothelial cells and pericytes partially contribute to this process.

PMID- 24444001
TI  - Carbon and nitrogen gain during the growth of orchid seedlings in nature.
AB  - For germination and establishment, orchids depend on carbon (C) and nutrients
      supplied by mycorrhizal fungi. As adults, the majority of orchids then appear to
      become autotrophic. To compare the proportional C and nitrogen (N) gain from
      fungi in mycoheterotrophic seedlings and in adults, here we examined in the field
      C and N stable isotope compositions in seedlings and adults of orchids associated
      with ectomycorrhizal and saprotrophic fungi. Using a new highly sensitive
      approach, we measured the isotope compositions of seedlings and adults of four
      orchid species belonging to different functional groups: fully and partially
      mycoheterotrophic orchids associated with narrow or broad sets of ectomycorrhizal
      fungi, and two adult putatively autotrophic orchids associated exclusively with
      saprotrophic fungi. Seedlings of orchids associated with ectomycorrhizal fungi
      were enriched in (13) C and (15) N similarly to fully mycoheterotrophic adults.
      Seedlings of saprotroph-associated orchids were also enriched in (13) C and (15)
      N, but unexpectedly their enrichment was significantly lower, making them hardly
      distinguishable from their respective adult stages and neighbouring autotrophic
      plants. We conclude that partial mycoheterotrophy among saprotroph-associated
      orchids cannot be identified unequivocally based on C and N isotope compositions
      alone. Thus, partial mycoheterotrophy may be much more widely distributed among
      orchids than hitherto assumed. 

PMID- 24444002
TI  - Visualization of the magnetic structure of sculpted three-dimensional cobalt
      nanospirals.
AB  - In this work, we report on the direct visualization of magnetic structure in
      sculpted three-dimensional cobalt (Co) nanospirals with a wire diameter of 20 nm
      and outer spiral diameter of 115 nm and on the magnetic interactions between the
      nanospirals, using aberration-corrected Lorentz transmission electron microscopy.
      By analyzing the magnetic domains in three dimensions at the nanoscale, we show
      that magnetic domain formation in the Co nanospirals is a result of the shape
      anisotropy dominating over the magnetocrystalline anisotropy of the system. We
      also show that the strong dipolar magnetic interactions between adjacent closely
      packed nanospirals leads to their magnetization directions adopting alternating
      directions to minimize the total magnetostatic energy of the system. Deviations
      from such magnetization structure can only be explained by analyzing the complex
      three-dimensional structure of the nanospirals. These nanostructures possess an
      inherent chirality due to their growth conditions and are of significant
      importance as nanoscale building blocks in magneto-optical devices. 

PMID- 24444003
TI  - Pharmacoeconomic burden in the treatment of psoriatic arthritis: from systematic
      reviews to real clinical practice studies.
AB  - The economic assessment of treatment options in a chronic and severe disease like
      Psoriatic Arthritis (PsA) is crucial to estimate the burden of costs. In
      particular, the impact of new costly medications such as biologic agents have
      been studied to figure this important aspect of a multifaceted disease. In a
      previous observational, longitudinal multicentre cost evaluation study, the
      results showed that biologic agents are cost-effective. This study was obtained
      from the real clinical practice and encompassed PsA patients refractory to
      traditional treatments. Similar data were also obtained from reviews analysis of
      Randomized Controlled Trials (RCTs). Recently, Cawson et al. performed a
      systematic review, network meta-analysis and economic evaluation of biological
      therapy for the management of active PsA. The review was conducted to identify
      relevant, recently published studies and the new trial data were synthesized, via
      a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the
      TNF-alpha inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC)
      response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and
      Severity Index (PASI). In particular the analysis showed that, on average,
      etanercept was the most cost-effective treatment and, at the National Institute
      for Health and Care Excellence willingness-to-pay threshold of between L20,000 to
      L30,000, etanercept is the preferred option. This study, as a systematic review,
      has been focused on main RCTs on active PsA treated by biological DMARDs and
      limitations to this analysis arise from a paucity of data on long-term follow up,
      as well as radiological progression and long-term safety. These interesting
      results reflected the important role of biologic agents in the management of PsA,
      highlighting their efficacy and cost-effectiveness. However, there are some unmet
      needs for pharmacoeconomic considerations based on prospective and/or on real
      clinical practice studies, as well as considering all the intriguing aspects of
      this challenging disease. 

PMID- 24444004
TI  - Vitamin D deficiency is associated with orthostatic hypotension in oldest-old
      women.
AB  - OBJECTIVES: Orthostatic hypotension, a condition that mostly affects 'oldest-old'
      (i.e. >=80 years) adults, is primarily explained by age-related dysfunction of
      blood pressure control. Vitamin D may contribute to blood pressure control. The
      aim of this study was to determine whether vitamin D deficiency is associated
      with orthostatic hypotension in oldest-old adults. DESIGN: Cross-sectional
      analysis at baseline of the EPIDOS study. SETTING: Five French areas.
      PARTICIPANTS: A total of 329 community-dwelling oldest-old women (mean age 83.3
      +/- 0.2 years). MAIN OUTCOMES MEASURES: Orthostatic hypotension was defined as a
      systolic blood pressure drop of >=20 mmHg and/or a diastolic blood pressure drop
      of >=10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a
      serum 25-hydroxyvitamin D (25OHD) concentration <=10 ng mL(-1) . Covariates
      included in the models were age, body mass index, diabetes mellitus, supine mean
      arterial pressure, number of drugs taken per day, use of antihypertensive or
      psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol
      consumption, serum concentrations of parathyroid hormone, calcium and creatinine
      and season of testing. RESULTS: Diastolic orthostatic hypotension was observed
      more often among women with vitamin D deficiency (19.2%) compared to those
      without (10.0%; P = 0.03). There was an inverse linear association between 25OHD
      concentration and change in diastolic blood pressure after 3 min of standing
      (adjusted beta = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated
      with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004],
      specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P =
      0.003). CONCLUSIONS: 25OHD deficiency was associated with orthostatic hypotension
      in oldest-old women, due to a greater drop in diastolic blood pressure on
      standing. This finding may lead to better understanding of the pathophysiology of
      falls in oldest-old adults with vitamin D deficiency.

PMID- 24444006
TI  - Cultural diversity among nursing students: reanalysis of the cultural awareness
      scale.
AB  - Nurses are educated to provide culturally competent care. Cultural competence
      begins with cultural awareness, a concept previously measured with the Cultural
      Awareness Scale (CAS). The purpose of this study was to reanalyze the CAS to
      determine construct validity and differences in cultural awareness among students
      of varying educational levels and experiences. The sample consisted of 150
      nursing students (92% female, 33.6% racial minorities). Confirmatory factor
      analysis yielded three factors (CFI = 0.868, TLI = 0.854, RMSEA = 0.065, and SRMR
      = 0.086). Cronbach's alpha ranged from 0.70 to 0.89. There were significant
      differences among educational levels, with lower division BSN students generally
      scoring higher than upper division and master's of science in nursing students.
      Students who had taken courses on cultural diversity or global health generally
      outscored those who had not taken such courses. Findings support the validity of
      the CAS and its applicability to research studies of cultural awareness in
      nursing.

PMID- 24444005
TI  - The effect of childhood cow's milk intake and HLA-DR genotype on risk of islet
      autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young.
AB  - BACKGROUND: Cow's milk intake has been inconsistently associated with islet
      autoimmunity (IA) and type 1 diabetes (T1D) development. Genetic and
      environmental factors may modify the effect of cow's milk on IA and T1D risk.
      METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) follows children at
      increased T1D risk of IA (presence of autoantibodies to insulin, GAD65, or IA-2
      twice in succession) and T1D development. We examined 1835 DAISY children with
      data on cow's milk intake: 143 developed IA, 40 subsequently developed T1D. Cow's
      milk protein and lactose intake were calculated from prospectively collected
      parent- and self-reported food frequency questionnaires (FFQ). High risk HLA-DR
      genotype: HLA-DR3/4,DQB1*0302; low/moderate risk: all other genotypes. We
      examined interactions between cow's milk intake, age at cow's milk introduction,
      and HLA-DR genotype in IA and T1D development. Interaction models contained the
      base terms (e.g., cow's milk protein and HLA-DR genotype) and an interaction term
      (e.g., cow's milk protein*HLA-DR genotype). RESULTS: In survival models adjusted
      for total calories, FFQ type, T1D family history, and ethnicity, greater cow's
      milk protein intake was associated with increased IA risk in children with
      low/moderate risk HLA-DR genotypes [hazard ratio (HR): 1.41, 95% confidence
      interval (CI): 1.08-1.84], but not in children with high risk HLA-DR genotypes.
      Cow's milk protein intake was associated with progression to T1D (HR: 1.59, CI:
      1.13-2.25) in children with IA. CONCLUSIONS: Greater cow's milk intake may
      increase risk of IA and progression to T1D. Early in the T1D disease process,
      cow's milk intake may be more influential in children with low/moderate genetic
      T1D risk.

PMID- 24444007
TI  - Insight into error hiding: exploration of nursing students' achievement goal
      orientations.
AB  - An estimated 50% of medication errors go unreported, and error hiding is costly
      to hospitals and patients. This study explored one issue that may facilitate
      error hiding. Descriptive statistics were used to examine nursing students'
      achievement goal orientations in a high-fidelity simulation course. Results
      indicated that although this sample of nursing students held high mastery goal
      orientations, they also held moderate levels of performance-approach and
      performance-avoidance goal orientations. These goal orientations indicate that
      this sample is at high risk for error hiding, which places the benefits that are
      typically gleaned from a strong mastery orientation at risk. Understanding
      variables, such as goal orientation, that can be addressed in nursing education
      to reduce error hiding is an area of research that needs to be further explored.
      This article discusses the study results and evidence-based instructional
      practices for this sample's achievement goal orientation profile.

PMID- 24444008
TI  - Preventing information overload: cognitive load theory as an instructional
      framework for teaching pharmacology.
AB  - Nursing students are challenged by content-laden curricula and learning
      environments that emphasize testing outcomes. Likewise, educators are challenged
      to support student-centered learning in a manner that encourages students to
      connect and act upon their personal motivations. This article describes the use
      of cognitive load theory (CLT) as an instructional design framework for an
      undergraduate pharmacology for nursing course. Guided by the principles of CLT,
      four instructional strategies were used in this course: (a) opening review
      activities, (b) providing students with lecture notes, (c) a "Top Five" prototype
      approach, and (d) deciphering "Need to Knows" from "Nice to Knows." Instructional
      style and strategies received positive student feedback and were found to promote
      a student-centered environment and active learning. On the basis of this
      feedback, cognitive load theory may be a successful and effective framework for
      undergraduate pharmacology and other nursing courses, thus assisting students and
      educators alike in overcoming obstacles imposed on learning environments.

PMID- 24444009
TI  - Integrating professional apprentices into an end-of-life course.
AB  - Nursing education faces several challenges in providing quality and meaningful
      education. Providing such an education is most important in teaching end-of-life
      care, as nurses are pivotal in helping patients to achieve a good death. A good
      death is often based on physical comfort, preparation for death, and completion
      of social and emotional tasks. Many obstacles hinder a patient's wishes about
      dying, including how nurses perceive their role in end-of-life care situations
      and knowing how to intervene on behalf of the patient. Therefore, nursing
      education needs to create meaningful and relevant learning experiences to enable
      future nurses to effectively care for the dying patient. To this endeavor, the
      Palliative and End-of-Life Care course described in this article integrated
      knowledge through the use of three professional apprenticeships: (a) acquiring
      and using knowledge and science (cognitive), (b) using clinical reasoning and
      skilled know-how (practice), and (c) ethical comportment and formation (moral
      reasoning).

PMID- 24444010
TI  - Advancing the science of research in nursing education: contributions of the
      critical decision method.
AB  - Advancing the science of nursing education will require the discipline to conduct
      research that investigates complex phenomena, such as students' clinical thinking
      and decision-making skills, using multiple methods. The research methods
      developed in other disciplines can provide nursing education researchers with new
      ways to investigate clinical teaching and learning in nursing. The critical
      decision method (CDM), derived from psychology and human factors engineering, is
      a technique by which researchers elicit experts' thinking and the cognitive work
      informing decision making in the context of practice. This article describes how
      the CDM was adapted to study nursing students' situation awareness, cues for
      action, and pattern recognition during clinical experiences. The CDM is a
      promising method for investigators to use to conduct research in nursing
      education and to inform the design of clinical experiences to promote these
      critical abilities.

PMID- 24444011
TI  - Academic dishonesty among nursing students.
AB  - This quantitative study identified sociodemographic and situational conditions
      that affected 336 nursing students' engagement in academic dishonesty, their
      attitudes regarding various forms of academic dishonesty, and the prevalence of
      academic dishonesty in which they engaged and witnessed. More than half of the
      participants reported cheating in the classroom and in the clinical settings. A
      positive relationship was found between the frequency of cheating in classroom
      and clinical settings. Results revealed differences in frequency of engagement in
      and attitudes toward academic dishonesty by gender, semester in the program, and
      ethnicity. Relationships were also found among peer behavior, personal beliefs
      and values, and frequency of engaging in academic dishonesty.

PMID- 24444012
TI  - Using simulations to identify nursing student behaviors: a longitudinal study of
      medication administration.
AB  - The Centers for Disease Control and Prevention recognizes adverse drug events as
      a serious public health problem. Nurses routinely administer patient medications
      and must be safe when delivering care. Typically, students are taught the
      traditional rights method (RM) of safe medication administration in the skills
      laboratory and through the use of high-fidelity simulation scenarios. The RM
      includes measures of ensuring the right patient, right medication, right dose,
      right time, and right route. This pilot study demonstrates changes in
      verification of the rights among junior and senior nursing students in four
      simulation scenarios over the course of one academic year. The findings suggest
      that students become more neglectful in verification of the rights prior to
      medication administration as they progress through the curriculum. This study
      should help educators identify significant focus areas for clinical supervisors,
      including the importance of increased verification of the rights of safe
      medication administration in the clinical setting.

PMID- 24444013
TI  - What matters most? Students' rankings of simulation components that contribute to
      clinical judgment.
AB  - As the pedagogy of health care simulation matures, the level of guidance provided
      and types of simulation components included increasingly vary. To prepare
      students for professional practice, one university embedded Tanner's model of
      clinical judgment within the nursing curricula and integrated simulations. There
      was interest in seeking students' opinions of "what matters most" in the design
      and delivery of simulations, which may vary from the academic's viewpoint. Senior
      undergraduate nursing students (N = 150) from three types of study programs rated
      11 simulation components in relation to clinical judgment. The three student
      groups rated all components above 2.9 on a 5-point Likert scale, with some
      variation across groups for component rankings. The highest ranking components
      for applying clinical judgment were facilitated debriefing, postsimulation
      reflection, and guidance by the academic. The lowest ranked components were
      patient case notes and briefing and orientation to the simulation area. Age and
      previous nursing experience did not influence the study variables.

PMID- 24444014
TI  - Theoretical studies on binding and specificity mechanisms of farnesyltransferase
      (FTase) and geranylgeranyltransferase type-I (GGTase-I) inhibitors by molecular
      modeling.
AB  - Farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) are
      two members of protein prenyltransferases, which play critical roles in lipid
      post-translational modifications. Potent inhibitors of FTase and GGTase-I have
      been confirmed to show favorable influence on the therapies of various diseases,
      such as cancers, malaria and Toxoplasmosis. However, designing highly specific
      inhibitors toward FTase or GGTase-I without influencing their binding affinity
      remains a big challenge. In this work, molecular docking, molecular dynamics (MD)
      simulations and MM/GBSA free energy calculations were employed to study the
      bindings of two highly selective inhibitors (lonafarnib and GGTI-2133) towards
      FTase or GGTase-I. The specificities of the studied inhibitors derived from the
      predicted binding free energies are consistent with the experimental data. The
      analysis of the energetic components illustrates that both the non-polar and
      polar interactions play critical roles in determining the specificity between
      FTase and GGTase-I. Moreover, the protein-inhibitor interaction spectra for the
      studied inhibitors were determined through the decomposition of the binding free
      energies, and the important residues for binding and specificity were
      highlighted. Our study provides useful information for the rational design of
      selective FTase or GGTase-I inhibitors. 

PMID- 24444015
TI  - Low-grade myxofibrosarcoma following a metal implantation in femur: a case
      report.
AB  - Myxofibrosarcoma is a myxoid variant of malignant fibrous histiocytoma that most
      commonly involves the extremities of elderly people. However, a primary
      myxofibrosarcoma with bone invasion in young adults is extremely rare. Herein, we
      report the case of a 31-year-old male with a gradually enlarging left thigh mass,
      who had a history of left femur fracture and received an open reduction and
      internal fixation with titanium alloy plates and screws 33 months previously.
      Imaging investigations revealed an irregularly shaped soft tissue mass around the
      left femur shaft and a partial bone defect in the middle one-third of the left
      femur. Pathological examination of the resected specimen showed a multi-nodular
      appearance, abundant myxoid matrix and elongated curvilinear capillaries.
      Immunohistochemical studies revealed that the tumor cells was positive for VIM
      and MDM2, and was negative for CK, MSA, SMA, DES, S-100 and CD34. Labeling index
      of Ki-67 was 25%. Based on the morphological finding and immunostaining, it was
      diagnosed as a low-grade myxofibrosarcoma. The clinical and imaging examinations
      did not reveal the evidence of a primary cancer elsewhere, and the patient had no
      personal or family history of malignancy. To our knowledge, this is the first
      case of a primary myxofibrosarcoma developed following a fracture and metal
      implantation in young adults. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1745984882113605.

PMID- 24444016
TI  - Characterization of vapor phase mercury released from concrete processing with
      baghouse filter dust added cement.
AB  - The fate of mercury (Hg) in cement processing and products has drawn intense
      attention due to its contribution to the ambient emission inventory. Feeding Hg
      loaded coal fly ash to the cement kiln introduces additional Hg into the kiln's
      baghouse filter dust (BFD), and the practice of replacing 5% of cement with the
      Hg-loaded BFD by cement plants has recently raised environmental and occupational
      health concerns. The objective of this study was to determine Hg concentration
      and speciation in BFD as well as to investigate the release of vapor phase Hg
      from storing and processing BFD-added cement. The results showed that Hg content
      in the BFD from different seasons ranged from 0.91-1.44 mg/kg (ppm), with 62-73%
      as soluble inorganic Hg, while Hg in the other concrete constituents were 1-3
      orders of magnitude lower than the BFD. Up to 21% of Hg loss was observed in the
      time-series study while storing the BFD in the open environment by the end of the
      seventh day. Real-time monitoring in the bench system indicated that high
      temperature and moisture can facilitate Hg release at the early stage. Ontario
      Hydro (OH) traps showed that total Hg emission from BFD is dictated by the air
      exchange surface area. In the bench simulation of concrete processing, only 0.4
      0.5% of Hg escaped from mixing and curing BFD-added cement. A follow-up headspace
      study did not detect Hg release in the following 7 days. In summary, replacing 5%
      of cement with the BFD investigated in this study has minimal occupational health
      concerns for concrete workers, and proper storing and mixing of BFD with cement
      can minimize Hg emission burden for the cement plant. 

PMID- 24444017
TI  - Mast cells protect from skin tumor development and limit tumor growth during
      cutaneous de novo carcinogenesis in a Kit-dependent mouse model.
AB  - Epidermal tumors belong to the most frequent type of neoplasms, and tumor
      associated accumulation of mast cells (MCs) has first been observed more than a
      century ago. Therefore, MCs have been implicated in tumor development and growth;
      however, the results regarding the role of MC in cutaneous de novo carcinogenesis
      are still controversially discussed. Here, we subjected MC-deficient Kit(W)
      /Kit(W-v) mice to chemical skin carcinogenesis. Tumors were induced using the
      carcinogen 7,12-dimethylbenz[a]-anthracene and subsequent treatment with the
      tumor promoter 12-tetradecanoyl-phorbol-13-acetat. The treatment resulted in
      pronounced inflammatory cell infiltrates that were diminished in MC-deficient
      animals. Unexpectedly, tumor development and growth was significantly increased
      in MC-deficient Kit(W) /Kit(W-v) mice. The repair of their MC deficiency by local
      adoptive transfer of MCs normalized tumor incidence and growth. The recruitment
      of skin-infiltrating immune cells, particularly of F4/80+ monocytes, Gr-1+
      granulocytes, B220+ B cells and CD8+ T lymphocytes, to sites of tumor development
      was, in part, also controlled by MCs. Recent evidence indicated the importance of
      local antitumor tissue immunity which prevents tumor development. These findings
      suggest a critical role for MCs in mediating these host antitumor immune
      responses in the skin. 

PMID- 24444018
TI  - Unraveling the role of Arg4 and Arg6 in the auto-inhibition mechanism of GSK3beta
      from molecular dynamics simulation.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is a multifunctional serine/threonine
      protein kinase that is involved in several biological processes including insulin
      and Wnt signaling pathways. GSK3beta can be phosphorylated by the protein kinase
      B (PKB). The mutations of Arg4 and Arg6 to alanine at N-terminal GSK3beta have
      been reported to impair its ability to autophosphorylate at Ser9. Despite the
      extensive experimental observations, the detailed mechanism for the auto
      inhibition of GSK3beta has not been rationalized at the molecular level. In this
      study, we have demonstrated the structural consequences of GSK3beta R4A and R6A
      mutations and the atomic changes that influenced the loss of PKB-binding
      affinity. Molecular dynamics simulation results suggested significant loss in
      atomic contacts in the R4A and R6A mutant systems compared to the wild-type
      system. Furthermore, we observed many notable changes (such as conformation,
      residues motions, hydrogen bonds, and binding free energy) in the mutated
      GSK3beta-PKB complexes. Loss of binding affinity in the mutated systems rendered
      the decrease in GSK3beta phosphorylation, which, in turn, impaired the auto
      inhibition of GSK3beta. The significant outcomes obtained from this study can
      explain the auto-inhibition of GSK3beta and maybe facilitate type 2 diabetes
      mellitus researches and in developing the potent drug therapies. 

PMID- 24444019
TI  - Marker-based estimates of relatedness and inbreeding coefficients: an assessment
      of current methods.
AB  - Inbreeding (F) of and relatedness (r) between individuals are now routinely
      calculated from marker data in studies in the fields of quantitative genetics,
      conservation genetics, forensics, evolution and ecology. Although definable in
      terms of either correlation coefficient or probability of identity by descent
      (IBD) relative to a reference, they are better interpreted as correlations in
      marker-based analyses because the reference in practice is frequently the current
      sample or population whose F and r are being estimated. In such situations,
      negative estimates have a biological meaning, a substantial proportion of the
      estimates are expected to be negative, and the average estimates are close to
      zero for r and equivalent to FIS for F. I show that although current r estimators
      were developed from the IBD-based concept of relatedness, some of them conform to
      the correlation-based concept of relatedness and some do not. The latter
      estimators can be modified, however, so that they estimate r as a correlation
      coefficient. I also show that F and r estimates can be misleading and become
      biased and marker dependent when a sample containing a high proportion of highly
      inbred and/or closely related individuals is used as reference. In analyses
      depending on the comparison between r (or F) estimates and a priori values
      expected under ideal conditions (e.g. for identifying genealogical relationship),
      the estimators should be used with caution. 

PMID- 24444020
TI  - Kinetics of browning, phenolics, and 5-hydroxymethylfurfural in commercial
      sparkling wines.
AB  - We analyzed the degree of browning (absorbance at 420 nm), the phenolics, and the
      5-hydroxymethylfurfural (5-HMF) content in six sparkling wines series kept at
      three temperatures (4, 16, and 20  degrees C) for over 2 years. Caffeic acid,
      trans-coutaric acid, p-coumaric acid, and 5-HMF were the compounds with the
      greatest correlation with browning and time. 5-HMF was the only compound that
      evolved linearly at all temperatures. We propose that 5-HMF is a better time
      temperature marker than the A420 parameter or phenolics, because it shows higher
      linearity with time at all temperatures, is more sensitive to temperature
      changes, and has lower variability. The kinetics of 5-HMF was studied showing a
      zero-order behavior. We propose mathematical models that wineries can use to
      predict the browning shelf life of their sparkling wines as a function of the
      storage time and temperature.

PMID- 24444021
TI  - A nanoscale characterization with electron microscopy of multilayered CrAlYN
      coatings: a singular functional nanostructure.
AB  - A combination of transmission electron microscopy techniques and spatially
      resolved microanalysis is used to investigate the nanostructure, constituting
      phases, and chemical elemental distribution in CrAlYN multilayered coatings. The
      location of the metallic elements and their chemical state are needed to
      understand their functional properties. Samples were prepared with variable Al (4
      12 at%) and Y (2-5 at%) contents by direct current reactive magnetron sputtering
      on silicon substrates using metallic targets and Ar/N2 mixtures under different
      deposition parameters (power applied to the target and rotation speed of the
      sample holder). The changes produced in the nanostructure and chemical
      distribution were investigated. Nanoscale resolution electron microscopy analysis
      has shown that these coatings present a singular nanostructure formed by
      multilayers containing at a certain periodicity nanovoids filled with molecular
      nitrogen. Spatially resolved energy dispersive spectroscopy and electron energy
      loss elemental mappings and profiles showed that the chromium, aluminum, and
      yttrium atoms are distributed in a sequential way following the position of the
      targets inside the deposition chamber. Analysis of the different atomic
      distribution and phases formed at the nanoscale is discussed depending on the
      deposition parameters. 

PMID- 24444022
TI  - An American mink (Neovison vison) transcriptome.
AB  - HiSeq2000 Illumina pair-end sequenced transcript data originating from a pool of
      four different tissues of a wild-type American mink yielded approximately 90 Gb
      of raw data. Subsequently, unique contigs were assembled by a combined approach
      using velvet and phrap. Of these assembled contigs, about 136 000 match the dog
      genome and nearly 30 000 contigs match the human transcriptome at more than 17
      000 unique gene locations. Gene annotation for these contigs was performed
      employing custom-made scripts run in combination with comparative sequence
      similarity search and alignment in the dog and human genome using blast
      algorithms. Transcripts representing five genes known to be associated with
      pigmentation were reliably aligned against large mink genomic contigs derived
      from BAC clones. Sequence comparison between transcript and genomic data revealed
      seven SNPs. In this study, we generated and annotated mink transcript sequences
      representing more than 16 000 known genes. This is the first comprehensive
      transcriptome for the American mink genome, which will facilitate further
      development in mink expression profiling studies and provide a good annotation
      basis in the perspectives of a whole genome sequencing project. The project was
      deposited at EMBL database with the accession number PRJEB1260.

PMID- 24444023
TI  - Multiple microRNAs derived from chemically synthesized precursors regulate
      thrombospondin 1 expression.
AB  - Thrombospondin 1 (THBS1) is a secreted protein with a variety of biological
      functions, including a potent anti-angiogenic activity and activation of latent
      transforming growth factor beta (TGF-beta). In many human cancers it is expressed
      at low levels, although mutations in the THBS1 gene have been rarely reported.
      Instead, the loss of THBS1 expression has been proposed to be due to
      transcriptional and post-transcriptional deregulations. In a systematic screen of
      predicted microRNA (miRNA) binding sites in the THBS1 3' untranslated region
      (UTR) we employed chemically synthesized pre-miRNAs-a new class of pre-miRNA
      mimics-to show that several miRNAs (let-7a, miR-18a, miR-29b, miR-194, and miR
      221) can modulate THBS1 expression at the post-transcriptional level. Sequence
      specific downregulation of THBS1 by let-7a, miR-18a or by a small interfering RNA
      induced TGF-beta1 and SMAD4 transcript levels. Ectopic expression of latent TGF
      beta1 reduced THBS1 protein expression and was associated with increased
      expression of let-7a, let-7-b, and miR-18a in cells. These data suggest an
      inverse correlation of THBS1 and latent TGF-beta1 expression levels possibly
      involving miRNAs. 

PMID- 24444024
TI  - PaTz groups for primary palliative care: reinventing cooperation between general
      practitioners and district nurses in palliative care: an evaluation study
      combining data from focus groups and a questionnaire.
AB  - BACKGROUND: PaTz (an acronym for 'PAlliatieve Thuis Zorg'; palliative care at
      home) is an intervention to improve palliative care provision and strengthen the
      generalist knowledge of palliative care. In PaTz general practitioners and
      district nurses meet on a regular basis to identify patients with palliative care
      needs and to discuss care for these patients. This study explores experiences
      with regard to collaboration between general practitioners and district nurses,
      and perceived benefits of and barriers for implementation of PaTz. METHODS: This
      study is conducted within the primary care setting. Participants were 24 general
      practitioners who filled in a questionnaire, and seven general practitioners,
      five district nurses and two palliative care consultants who attended one of two
      focus groups. RESULTS: PaTz led to improved collaboration. Participants felt
      informational and emotional support from other PaTz participants. Also they felt
      that continuity of care was enhanced by PaTz. Practical recommendations for
      implementation were: meetings every 6 to 8 weeks, regular attendance from both
      general practitioners and district nurses, presence of a palliative care
      consultant, and a strong chairman. CONCLUSIONS: PaTz is successful in enhancing
      collaboration in primary palliative care and easy to implement. Participants felt
      it improved continuity of care and knowledge on palliative care. Further research
      is needed to investigate whether patient and carer outcomes improve.

PMID- 24444025
TI  - Protective effect of Aloe vera gel on the permeability transition pore in the
      inner membrane of rat liver mitochondria in vitro.
AB  - OBJECTIVE: Aloe vera is a perennial drought resisting, succulent plant belonging
      to the zanthorrhoeaceae family which historically has been used for a variety of
      medicinal purposes. This study seeks to determine the effect of varying
      concentrations of Aloe vera gel (50, 100, 150, 250, and 350 ug/ml) on
      mitochondrial permeability transition pore (MPTP) in rat liver mitochondria (RLM)
      (in vitro). METHODS: Fresh Aloe gel was prepared daily from the Aloe vera leaf
      and the effect of the gel on mitochondrial membrane permeability transition pore
      opening was estimated in vitro using the spectrophotometric method of Lapidus and
      Sokolove. RESULTS: Varying concentrations of Aloe vera gel (50, 100, 150, 250,
      and 350 ug/ml) induced (insignificantly at p < 0.05) the opening of the
      mitochondrial permeability transition pore in a concentration dependent manner in
      the absence of calcium (Delta540 nm as -0.020 +/- 0.008, -0.021 +/- 0.009, -0.031
      +/- 0.013, -0.031 +/- 0.014, -0.034 +/- 0.014 respectively) when compared with
      the control (-0.016 +/- 0.009). In the presence of calcium, the various
      concentrations of Aloe vera gel further opened the MMPT pore with the highest
      effect noticed at 350 ug/ml concentration. CONCLUSIONS: These findings indicate
      that Aloe vera gel modulates the mitochondrial pore opening by further increasing
      the effect of calcium. This effect is needed in situations that requires tissue
      wastage such as in cancer treatment.

PMID- 24444026
TI  - Chemical composition, and in vitro antibacterial and antifungal activity of an
      alkaloid extract from Crinum angustum Steud.
AB  - In the search for novel antibacterial agents against multidrug-resistant
      bacteria, an alkaloid extract obtained from whole plants of Crinum angustum
      Steud., containing six different groups of alkaloids, was analysed by using gas
      chromatography/mass spectrometry, and its in vitro activity against American Type
      Culture Collection bacterial strains and clinical isolates was evaluated. The
      antimicrobial activity of the extract was tested against nine standard strains of
      microorganisms and two drug-resistant clinical isolates, methicillin-resistant
      Staphylococcus aureus and carbapenemase-producing Klebsiella pneumoniae. The
      extract exhibited a significant activity against six of the examined strains of
      microorganisms. Antibacterial activity was more pronounced on Gram-positive
      bacteria than on Gram-negative bacteria, and IC50 values ranged from 156 to 625
      MUg/mL. Mycostatic activity against Candida albicans was also found, with an IC50
      of 78 MUg/mL after 48 h of incubation . Promising results were also obtained from
      tests carried out on both clinical isolates investigated.

PMID- 24444027
TI  - Bullous lesion with central umbilication in leukemia.

PMID- 24444028
TI  - Persistent telangiectatic erythema following nostril piercing.

PMID- 24444029
TI  - Primary cutaneous gammadelta T-cell lymphoma following mycosis fungoides.

PMID- 24444030
TI  - Current issues in the evolutionary ecology of ant-plant symbioses.
AB  - Ant-plant symbioses involve plants that provide hollow structures specialized for
      housing ants and often food to ants. In return, the inhabiting ants protect
      plants against herbivores and sometimes provide them with nutrients. Here, we
      review recent advances in ant-plant symbioses, focusing on three areas. First,
      the nutritional ecology of plant-ants, which is based not only on plant-derived
      food rewards, but also on inputs from other symbiotic partners, in particular
      fungi and possibly bacteria. Food and protection are the most important
      'currencies' exchanged between partners and they drive the nature and evolution
      of the relationships. Secondly, studies of conflict and cooperation in ant-plant
      symbioses have contributed key insights into the evolution and maintenance of
      mutualism, particularly how partner-mediated feedbacks affect the specificity and
      stability of mutualisms. There is little evidence that mutualistic ants or plants
      are under selection to cheat, but the costs and benefits of ant-plant
      interactions do vary with environmental factors, making them vulnerable to
      natural or anthropogenic environmental change. Thus, thirdly, ant-plant symbioses
      should be considered good models for investigating the effects of global change
      on the outcome of mutualistic interactions.

PMID- 24444031
TI  - Association between mid- to late life physical fitness and dementia: evidence
      from the CAIDE study.
AB  - OBJECTIVES: This study investigated the association between perceived physical
      fitness at midlife, changes in perceived fitness during the three decades from
      mid- to late life and dementia risk. DESIGN: Prospective cohort study. SETTING:
      Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study.
      SUBJECTS: Subjects were selected from four independent, random samples of
      population-based cardiovascular surveys and were first examined in 1972, 1977,
      1982 or 1987, when they were on average 50 years old. The CAIDE target population
      included 3559 individuals. A random sample of 2000 individuals still alive in
      1997 was drawn for re-examinations (performed in 1998 and 2005-2008) that
      consisted of cognitive assessments, with 1511 subjects participating in at least
      one re-examination. Dementia diagnoses were also confirmed from national
      registers for the entire target population. MAIN OUTCOME MEASURE: All-cause
      dementia. RESULTS: Poor physical fitness at midlife was associated with increased
      dementia risk in the entire target population [hazard ratio (HR), 1.5; 95%
      confidence interval (CI), 1.1-2.0]. In participants, odds ratio (OR) was 2.0 (95%
      CI, 0.9-4.0). This association was significant in apolipoprotein E epsilon4
      allele (APOEepsilon4) noncarriers (OR, 4.3; 95% CI, 1.4-13.3), men (HR, 1.8; 95%
      CI, 1.1-3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3-6.6). A
      decline in fitness after midlife was also associated with dementia (OR, 3.0; 95%
      CI, 1.7-5.1), which was significant amongst both men and women and more
      pronounced in APOEepsilon4 carriers (OR, 4.4; 95% CI, 2.1-9.1). CONCLUSIONS:
      Perceived poor physical fitness reflects a combination of biological and
      lifestyle-related factors that can increase dementia risk. A simple question
      about perceived physical fitness may reveal at-risk individuals who could benefit
      from preventive interventions.

PMID- 24444032
TI  - Synthesis of a miniature lipoarabinomannan.
AB  - An analog of Mycobacterium tuberculosis lipoarabinomannan (LAM) has been
      synthesized containing the characteristic structures of all of its three major
      components; that is, a mannosylated phosphatidylinositol moiety, an oligomannan,
      and an oligoarabinan. A highly convergent strategy was developed that is
      applicable to the synthesis of other LAM analogs. The synthetic miniature LAM
      should be useful for various biological studies. 

PMID- 24444033
TI  - Musashi1 regulates survival of hepatoma cell lines by activation of Wnt
      signalling pathway.
AB  - BACKGROUND & AIMS: Musashi1 (MSI1) belongs to the RNA-binding protein (RBP)
      family, with functions as translational activator or suppressor of specifically
      bound mRNA. However, its function in hepatocellular carcinoma (HCC) has been
      deeply unexplored. Here, we investigated the role of MSI1 for proliferation and
      tumourigenesis in HCC. METHODS: The expression of MSI1 in HCC tissues was
      examined by immunohistochemistry and western blotting. The effects of MSI1
      overexpression and silencing on cell proliferation, cell viability, tumoursphere
      and tumour formation of HCC were explored. RESULTS: In this study, we initially
      reported that MSI1 was upregulated in HCC. Overexpression of MSI1 in HepG2 cell
      lines resulted in significantly promoted cell growth, tumour formation and cell
      cycle progression. Consistently, knockdown of MSI1 in Huh7 cell lines remarkably
      inhibited cell growth and tumour formation, and caused cell cycle arrest at the
      G1/S transition. Dual-luciferase assays indicated that MSI1 activated Wnt signal
      pathway, and APC and DKK1 were direct targets of MSI1. CONCLUSION: Taken
      together, these findings indicate that an oncogenic role of MSI1 in HCC may be
      through modulation of cell growth and cell cycle by activating Wnt pathway via
      direct downregulation of APC and DKK1.

PMID- 24444034
TI  - Systematic review, network meta-analysis and economic evaluation of biological
      therapy for the management of active psoriatic arthritis.
AB  - BACKGROUND: An updated economic evaluation was conducted to compare the cost
      effectiveness of the four tumour necrosis factor (TNF)-alpha inhibitors
      adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic
      arthritis (PsA) where response to standard treatment has been inadequate.
      METHODS: A systematic review was conducted to identify relevant, recently
      published studies and the new trial data were synthesised, via a Bayesian network
      meta-analysis (NMA), to estimate the relative efficacy of the TNF-alpha
      inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response,
      Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity
      Index (PASI). A previously developed economic model was updated with the new meta
      analysis results and current cost data. The model was adapted to delineate
      patients by PASI 50%, 75% and 90% response rates to differentiate between
      psoriasis outcomes. RESULTS: All four licensed TNF-alpha inhibitors were
      significantly more effective than placebo in achieving PsARC response in patients
      with active PsA. Adalimumab, etanercept and infliximab were significantly more
      effective than placebo in improving HAQ scores in patients who had achieved a
      PsARC response and in improving HAQ scores in PsARC non-responders. In an
      analysis using 1,000 model simulations, on average etanercept was the most cost
      effective treatment and, at the National Institute for Health and Care Excellence
      willingness-to-pay threshold of between L20,000 to L30,000, etanercept is the
      preferred option. CONCLUSIONS: The economic analysis agrees with the conclusions
      from the previous models, in that biologics are shown to be cost-effective for
      treating patients with active PsA compared with the conventional management
      strategy. In particular, etanercept is cost-effective compared with the other
      biologic treatments.

PMID- 24444035
TI  - GOLPH3 predicts survival of colorectal cancer patients treated with 5
      fluorouracil-based adjuvant chemotherapy.
AB  - BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) has been validated as a potent
      oncogene involved in the progression of many types of solid tumors, and its
      overexpression is associated with poor clinical outcome in many cancers. However,
      it is still unknown the association of GOLPH3 expression with the prognosis of
      colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based
      adjuvant chemotherapy. METHODS: The expression of GOLPH3 was determined by qRT
      PCR and immunohistochemistry in colorectal tissues from CRC patients treated with
      5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with
      clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5
      FU sensitivity were examined in CRC cell lines. RESULTS: GOLPH3 expression was
      elevated in CRC tissues compared with matched adjacent noncancerous tissues.
      Kaplan-Meier survival curves indicated that high GOLPH3 expression was
      significantly associated with prolonged disease-free survival (DFS, P = 0.002)
      and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant
      chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was
      an independent prognostic factor for DFS in CRC patients treated with 5-FU-based
      chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression
      of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA
      mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced
      apoptosis. CONCLUSIONS: Our results suggest that GOLPH3 is associated with
      prognosis in CRC patients treated with postoperative 5-FU-based adjuvant
      chemotherapy, and may serve as a potential indicator to predict 5-FU
      chemosensitivity.

PMID- 24444037
TI  - Kinetic characterization of fragment binding in AmpC beta-lactamase by high
      throughput molecular simulations.
AB  - Small molecules used in fragment-based drug discovery form multiple, promiscuous
      binding complexes difficult to capture experimentally. Here, we identify such
      binding poses and their associated energetics and kinetics using molecular
      dynamics simulations on AmpC beta-lactamase. Only one of the crystallographic
      binding poses was found to be thermodynamically favorable; however, the ligand
      shows several binding poses within the pocket. This study demonstrates free
      binding molecular simulations in the context of fragment-to-lead development and
      its potential application in drug design. 

PMID- 24444036
TI  - Bioprosthetic heart valves of the future.
AB  - Glutaraldehyde-fixed bioprosthetic heart valves (GBHVs), derived from pigs or
      cows, undergo structural valve deterioration (SVD) over time, with calcification
      and eventual failure. It is generally accepted that SVD is due to chemical
      processes between glutaraldehyde and free calcium ions in the blood. Valve
      companies have made significant progress in decreasing SVD from calcification
      through various valve chemical treatments. However, there are still groups of
      patients (e.g., children and young adults) that have accelerated SVD of GBHV.
      Unfortunately, these patients are not ideal patients for valve replacement with
      mechanical heart valve prostheses as they are at high long-term risk from
      complications of the mandatory anticoagulation that is required. Thus, there is
      no "ideal" heart valve replacement for children and young adults. GBHVs represent
      a form of xenotransplantation, and there is increasing evidence that SVD seen in
      these valves is at least in part associated with xenograft rejection. We review
      the evidence that suggests that xenograft rejection of GBHVs is occurring, and
      that calcification of the valve may be related to this rejection. Furthermore, we
      review recent research into the transplantation of live porcine organs in non
      human primates that may be applicable to GBHVs and consider the potential use of
      genetically modified pigs as sources of bioprosthetic heart valves. 

PMID- 24444038
TI  - Fitness and physical activity in youth with type 1 diabetes mellitus in good or
      poor glycemic control.
AB  - BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) may experience poor
      muscle health as a result of chronic hyperglycemia. Despite this, muscle function
      in children with T1DM with good or poor glycemic control has yet to be examined
      in detail. OBJECTIVE: To assess differences in muscle-related fitness variables
      in children with T1DM with good glycemic control (T1DM-G), as well as those with
      poor glycemic control (T1DM-P), and non-diabetic, healthy controls. SUBJECTS:
      Eight children with T1DM-G [glycosylated hemoglobin (HbA1c) <= 7.5% for 9
      months], eight children with T1DM-P (HbA1c >= 9.0% for 9 months), and eight
      healthy controls completed one exercise session. METHODS: Anaerobic and aerobic
      muscle functions were assessed with a maximal isometric grip strength test, a
      Wingate test, and an incremental continuous cycling test until exhaustion. Blood
      samples were collected at rest to determine HbA1c at the time of testing.
      Physical activity was monitored over 7 d using accelerometry. RESULTS: Children
      with T1DM-P displayed lower peak oxygen consumption (VO2peak ) values (mL/kg/min)
      compared to healthy controls (T1DM-P: 33.2 +/- 5.6, controls: 43.5 +/- 6.3, p <
      0.01), while T1DM-G (43.5 +/- 6.3) had values similar to controls and T1DM-P.
      There was a negative relationship between VO2peak and HbA1c% (r = -0.54, p <
      0.01). All groups were similar in all other fitness variables. There were no
      group differences in physical activity variables. CONCLUSION: Children with T1DM
      G did not display signs of impaired muscle function, while children with T1DM-P
      have signs of altered aerobic muscle capacity.

PMID- 24444039
TI  - Should zygote intrafallopian transfer be offered to all patients with unexplained
      repeated in-vitro fertilization cycle failures?
AB  - BACKGROUND: One of the suggest strategy for patients with repeated implantation
      failure (RIF) is zygote intrafallopian transfer (ZIFT). However, no data exist
      regarding to the issue of when and under which circumstances should ZIFT be
      offered to patients with RIF? We therefore aimed to examine whether repeated
      implantation failure (RIF) patients characteristics or their previous controlled
      ovarian hyperstimulation (COH) variables may differentiate between those who will
      conceive following a ZIFT cycle and those who will not. METHODS: Forty seven
      consecutive women admitted to our IVF unit during a 7 year period, who underwent
      ZIFT for RIF, were included. Ovarian stimulation characteristics, number of
      oocytes retrieved and number and quality of zygotes/embryos transferred were
      assessed and compared between the ZIFT cycle and the previous IVF/ICSI cycle and
      between those who conceived following the ZIFT cycle and those who did not.
      RESULTS: Twelve clinical pregnancies (clinical pregnancy rate- 25.5%) were
      recorded following the ZIFT cycle. Those who benefit from ZIFT were young
      patients (<=31 yrs), who underwent <=6 cycle attempts, yielding over eight 2PN
      embryos with low (<=0.4) ratio of number of top-quality embryos to total 2PN
      embryos. Moreover, in those destined for a ZIFT cycle, only those with >7 2PN
      embryo should undergo a transfer of at least five 2PN embryos. CONCLUSIONS:
      Further large prospective studies are needed to identify the specific
      characteristics of RIF women who may benefit from ZIFT.

PMID- 24444041
TI  - Stepwise decrease of fluorescence versus sequential photobleaching in a single
      multichromophoric system.
AB  - For individual molecules from the newly synthesized calix[4]arene tethered
      perylene bisimide (PBI) trimer, we studied the emitted fluorescence intensity as
      a function of time. Owing to the zigzag arrangement of PBI dyes in these trimers,
      the polarization state of the emission provides directly information about the
      emitting subunit within the trimer. Interestingly, we observed emission from all
      neutral subunits within a trimer rather than exclusively from the subunit with
      the lowest site energy. This can be understood in terms of thermally activated
      uphill energy transfer that repopulates the higher energetic chromophores.
      Together with the simultaneously recorded polarization-resolved emission spectra,
      this reveals that the emission from a multichromophoric system is governed by a
      complex interplay between the temporal variations of the photophysical parameters
      of the subunits, bidirectional hopping processes within the trimer, and
      unavoidable photobleaching. Moreover, it is demonstrated that the typically
      observed stepwise decrease of the signal from a multichromophoric system does not
      necessarily reflect sequential bleaching of the individual chromophores within
      the macromolecule. 

PMID- 24444040
TI  - Cruciferous vegetables consumption and the risk of ovarian cancer: a meta
      analysis of observational studies.
AB  - BACKGROUND: To quantify the effect of cruciferous vegetable consumption on the
      incidence of ovarian cancer by meta-analyzing the existing observational studies
      and provides quantitative and high-level evidence. METHODS: A detailed literature
      search of Medline and EMBASE for all relevant papers published. A meta-analysis
      was conducted for the association between cruciferous vegetable consumption and
      risk of ovarian cancer. RESULTS: A total of 4,306 cases in 375,562 controls in 11
      independent studies were identified in this current meta-analysis. The result of
      this current meta-analysis, including 6 case-control and 5 cohort studies,
      indicated that cruciferous vegetable intake was associated with a reduced risk of
      ovarian cancer. Cruciferous vegetable consumption was associated with a reduced
      risk of ovarian cancer in case-control studies (RR=0.84; 95% CI, 0.75-0.94) but
      not in cohort studies (RR=1.00; 95% CI, 0.85-1.11). CONCLUSIONS: The results from
      this meta-analysis of observational studies demonstrate that cruciferous
      vegetable consumption is a prospective factor of the ovarian cancer. However,
      more in-depth studies are warranted to report more detailed results, including
      other specific vegetables within the cruciferous vegetable family. VIRTUAL
      SLIDES: The virtual slide (s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1116708293115581.

PMID- 24444042
TI  - CD44-targeted docetaxel conjugate for cancer cells and cancer stem-like cells: a
      novel hyaluronic acid-based drug delivery system.
AB  - A CD44-targeted macromolecular conjugate of docetaxel was prepared via a pH
      sensitive linkage to hyaluronic acid and was characterized using NMR, gel
      permeation chromatography, and differential scanning calorimetry. The conjugated
      species were further evaluated in terms of drug release, cytotoxicity, cellular
      uptake, cell cycle inhibition, and subacute toxicity in mice. Cellular
      microscopic studies revealed that CD44-expressing cells including MCF-7 cancer
      stem cells and MDA-MB-231 metastatic breast cancer cells had internalized the
      conjugates via a selective receptor-mediated mechanism, leading to cell cycle
      arrest in the G2/M phase. Hyaluronic acid-docetaxel conjugates showed specific
      toxicity only in CD44-expressing cells in vitro, along with a decreased risk of
      neutropenia and dose-dependent mortality in vivo. Hyaluronic acid-drug conjugates
      represent a promising and efficient platform for solubilization of sparingly
      soluble molecules as well as active and selective targeted delivery to cancer
      cells and cancer stem cells. 

PMID- 24444043
TI  - Gold nanoparticle uptake in whole cells in liquid examined by environmental
      scanning electron microscopy.
AB  - The size of gold nanoparticles (AuNPs) can influence various aspects of their
      cellular uptake. Light microscopy is not capable of resolving most AuNPs, while
      electron microscopy (EM) is not practically capable of acquiring the necessary
      statistical data from many cells and the results may suffer from various
      artifacts. Here, we demonstrate the use of a fast EM method for obtaining high
      resolution data from a much larger population of cells than is usually feasible
      with conventional EM. A549 (human lung carcinoma) cells were subjected to uptake
      protocols with 10, 15, or 30 nm diameter AuNPs with adsorbed serum proteins.
      After 20 min, 24 h, or 45 h, the cells were fixed and imaged in whole in a thin
      layer of liquid water with environmental scanning electron microscopy equipped
      with a scanning transmission electron microscopy detector. The fast preparation
      and imaging of 145 whole cells in liquid allowed collection of nanoscale data
      within an exceptionally small amount of time of ~80 h. Analysis of 1,041 AuNP
      filled vesicles showed that the long-term AuNP storing lysosomes increased their
      average size by 80 nm when AuNPs with 30 nm diameter were uptaken, compared to
      lysosomes of cells incubated with AuNPs of 10 and 15 nm diameter. 

PMID- 24444044
TI  - Hangover research needs: proceedings of the 5th Alcohol Hangover Research Group
      meeting.

PMID- 24444045
TI  - Rapid increase in dispersal during range expansion in the invasive ladybird
      Harmonia axyridis.
AB  - The evolutionary trajectories associated with demographic, genetic and spatial
      disequilibrium have become an issue of growing interest in population biology.
      Invasive species provide unique opportunities to explore the impact of recent
      range expansion on life-history traits, making it possible to test for a spatial
      arrangement of dispersal abilities along the expanding range, in particular. We
      carried out controlled experiments in laboratory conditions to test the
      hypothesis of an increase in dispersal capacity with range expansion in Harmonia
      axyridis, a ladybird that has been invading Europe since 2001. We found a marked
      increase in the flight speed of the insects from the core to the front of the
      invasion range in two independent sampling transects. By contrast, we found that
      two other traits associated with dispersal (endurance and motivation to fly off)
      did not follow the same spatial gradient. Our results provide a striking
      illustration of the way in which predictable directional genetic changes may
      occur rapidly for some traits associated with dispersal during biological
      invasions. We discuss the consequences of our results for invasion dynamics and
      the evolutionary outcomes of spatially expanding populations.

PMID- 24444046
TI  - Hospital-based HIV/HSV-2 seroprevalence among male patients with anal disease in
      Korea: cross sectional study.
AB  - BACKGROUND: This study aimed to identify the characteristics of HIV and herpes
      simplex virus (HSV)-2 seroprevalence in male patients with anal disease. METHODS:
      HIV seroprevalence was estimated for different age groups of male patients with
      anal disease who were treated at Songdo colorectal hospital in Korea between 2001
      and 2011. HIV seroprevalence of patients with anal disease was compared with that
      of patients with nonanal disease for each year from 2007 to 2011. HSV-2 antibody
      tests were conducted on 2,038 HIV-tested male patients with anal disease in 2009.
      RESULTS: For 11 years from 2001, HIV seroprevalence differed significantly by age
      group (P < 0.001) and was highest in the group aged <20 years. From 2007 to 2011,
      HIV seroprevalence in patients with anal disease was 7.6/10,000-13.3/10,000 and
      that in patients with nonanal disease was 0-0.9/10,000. HSV-2 seroprevalence
      among patients with anal disease was 24.0%, and only one patient with HIV and HSV
      2 was observed. CONCLUSIONS: HIV seroprevalencein male patients with anal disease
      was significantly higher than that for other diseases. HSV-2 seroprevalence was
      similar to that in the general male population. Implementation of the current HIV
      surveillance system for male patients at colorectal hospitals is necessary to
      help prevent HIV transmission.

PMID- 24444047
TI  - Evolving guidelines in the use of topical nonsteroidal anti-inflammatory drugs in
      the treatment of osteoarthritis.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard
      treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to
      an elevated risk for cardiovascular and gastrointestinal adverse events and renal
      toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to
      oral formulations while reducing widespread systemic drug exposure, which may
      provide a benefit in terms of safety and tolerability. As a result, European
      treatment guidelines have, for many years, recommended the use of topical NSAIDs
      as a safe and effective treatment option for OA. Following the recent approval of
      several topical NSAID formulations by the US Food and Drug Administration, US
      treatment guidelines are increasingly recommending the use of topical NSAIDs as
      an alternative therapy and, in some cases, as a first-line option for OA. This
      commentary summarizes OA treatment guidelines that are currently available and
      discusses their potential evolution with regard to the increased inclusion of
      topical NSAIDs.

PMID- 24444048
TI  - Established and novel disease-modifying treatments in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous
      system, resulting in inflammatory demyelination and axonal and neuronal injury.
      New diagnostic criteria that incorporate magnetic resonance imaging have resulted
      in earlier and more accurate diagnosis of MS. Several immunomodulatory and
      immunosuppressive therapeutic agents are available for relapsing forms of MS,
      which allow individualized treatment based upon the benefits and risks. Disease
      modifying therapies introduced in the 1990s, the beta-interferons and glatiramer
      acetate, have an established track record of efficacy and safety, although they
      require administration via injection. More recently, monoclonal antibodies have
      been engineered to act through specific mechanisms such as blocking alpha-4
      integrin interactions (natalizumab) or lysing cells bearing specific markers, for
      example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can
      be highly efficacious, but sometimes have serious potential complications
      (natalizumab is associated with progressive multifocal leukoencephalopathy;
      alemtuzumab is associated with the development of new autoimmune disorders).
      Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate,
      approved for MS treatment from 2010 onwards) provide efficacy, tolerability and
      convenience; however, as yet, there are no long-term postmarketing efficacy and
      safety data in a general MS population. Because of this lack of long-term data,
      in some cases, therapy is currently initiated with the older, safer injectable
      medications, but patients are monitored closely with the plan to switch therapies
      if there is any indication of a suboptimal response or intolerance or lack of
      adherence to the initial therapy. For patients with MS who present with highly
      inflammatory and potentially aggressive disease, the benefit-to-risk ratio may
      support initiating therapy using a drug with greater potential efficacy despite
      greater risks (e.g. fingolimod or natalizumab if JC virus antibody-negative). The
      aim of this review is to discuss the clinical benefits, mechanisms of action,
      safety profiles and monitoring strategies of current MS disease-modifying
      therapies in clinical practice and of those expected to enter the market in the
      near future.

PMID- 24444049
TI  - Worldwide frequency distribution of the 'Gait keeper' mutation in the DMRT3 gene.
AB  - For centuries, domestic horses have represented an important means of transport
      and served as working and companion animals. Although their role in
      transportation is less important today, many horse breeds are still subject to
      intense selection based on their pattern of locomotion. A striking example of
      such a selected trait is the ability of a horse to perform additional gaits other
      than the common walk, trot and gallop. Those could be four-beat ambling gaits,
      which are particularly smooth and comfortable for the rider, or pace, used mainly
      in racing. Gaited horse breeds occur around the globe, suggesting that gaitedness
      is an old trait, selected for in many breeds. A recent study discovered that a
      nonsense mutation in DMRT3 has a major impact on gaitedness in horses and is
      present at a high frequency in gaited breeds and in horses bred for harness
      racing. Here, we report a study of the worldwide distribution of this mutation.
      We genotyped 4396 horses representing 141 horse breeds for the DMRT3 stop
      mutation. More than half (2749) of these horses also were genotyped for a SNP
      situated 32 kb upstream of the DMRT3 nonsense mutation because these two SNPs are
      in very strong linkage disequilibrium. We show that the DMRT3 mutation is present
      in 68 of the 141 genotyped horse breeds at a frequency ranging from 1% to 100%.
      We also show that the mutation is not limited to a geographical area, but is
      found worldwide. The breeds with a high frequency of the stop mutation (>50%) are
      either classified as gaited or bred for harness racing.

PMID- 24444050
TI  - Assessment of protective effects of glucosamine and N-acetyl glucosamine against
      DNA damage induced by hydrogen peroxide in human lymphocytes.
AB  - The antigenotoxic activity of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc)
      in human peripheral lymphocytes exposed to oxidative stress was investigated.
      Human lymphocytes were treated with different concentrations of these aminosugars
      (0, 2.5, 5, 10, 20 and 40 mM) and 25 uM H2O2 simultaneously and evaluated by
      single cell gel electrophoresis technique (Comet assay). The single cells were
      analyzed using "TriTek Cometscore version 1.5" software and the data were
      presented as % DNA in tail. Both GlcN and GlcNAc at examined concentrations (2.5,
      5, 10, 20 and 40 mM) did not reveal any genotoxicity compared to the vehicle
      control (PBS). Glucosamine at all concentrations (2.5, 5, 10, 20 and 40 mM)
      showed a significant protective activity (% DNA in tail ranging from 16.07 +/-
      0.85 to 5.47 +/- 0.26, p < 0.001) against H2O2 induced DNA damage (% DNA in tail
      = 38 +/- 0.65) while its N-acetylated analog only indicated a slight DNA
      protection at concentration of 40 mM (% DNA in tail = 33.4 +/- 1.17, p < 0.01).
      We concluded that GlcN at tested concentrations exhibited potent antigenotoxic
      effect and its protection activity might be related to the presence of 2-NH2
      moiety in its chemical backbone.

PMID- 24444051
TI  - Xenotransplantation literature update, November-December 2013.

PMID- 24444052
TI  - Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic
      interactions between microorganisms within a shared epiphytic microbiome on
      Triticum and Brassica seeds.
AB  - In order to address the hypothesis that seeds from ecologically and
      geographically diverse plants harbor characteristic epiphytic microbiota, we
      characterized the bacterial and fungal microbiota associated with Triticum and
      Brassica seed surfaces. The total microbial complement was determined by
      amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific
      microorganisms were quantified by qPCR. Bacteria and fungi corresponding to
      operational taxonomic units (OTU) that were identified in the sequencing study
      were isolated and their interactions examined. A total of 5477 OTU were observed
      from seed washes. Neither total epiphytic bacterial load nor community
      richness/evenness was significantly different between the seed types; 578 OTU
      were shared among all samples at a variety of abundances. Hierarchical clustering
      revealed that 203 were significantly different in abundance on Triticum seeds
      compared with Brassica. Microorganisms isolated from seeds showed 99-100%
      identity between the cpn60 sequences of the isolates and the OTU sequences from
      this shared microbiome. Bacterial strains identified as Pantoea agglomerans had
      antagonistic properties toward one of the fungal isolates (Alternaria sp.),
      providing a possible explanation for their reciprocal abundances on both Triticum
      and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and
      fungal microbiota and revealed a core seed-associated microbiota shared between
      diverse plant genera. 

PMID- 24444055
TI  - Predicting medication persistence to buprenorphine transdermal system.
AB  - OBJECTIVES: Persistence, the duration a patient remains on therapy, in chronic,
      symptomatic conditions plays an important role in therapy effectiveness.
      Understanding the duration and patient factors associated with prescribed
      medication persistence is, therefore, an important step toward better treatment
      and health outcomes for patients. In the following study, an analysis of such
      factors associated with buprenorphine transdermal system (BTDS) persistence was
      conducted utilizing a large US private practitioner and pharmacy claims database
      and is herein reported. METHODS: Patients aged >= 18 years initiating BTDS during
      January 1, 2011-November 30, 2011 were identified in the IMS Private Practitioner
      Medical Claims and Pharmacy Claims databases. An index date was defined as the
      first prescription of BTDS during the studied interval. During the preindex
      period, Charlson Comorbidity Index (CCI), chronic pain-related conditions, and
      prior medication use were assessed. Concomitant medications and various treatment
      patterns (eg, last dose strength and dose adjustments) were assessed in the
      postindex 6-month period. Persistence was measured as the duration of BTDS from
      initiation to the 1st >28-day refill gap in the postindex 6-month period.
      Descriptive statistical and survival analysis was used to assess the predictors
      of BTDS persistence. RESULTS: During the study period, 10,457 patients newly
      treated with BTDS were identified. Patients' mean (+/- SD) age was 54.5 (+/-
      15.2) years; 69.9% were women, and the mean (+/- SD) CCI was 1 (+/- 1.4).
      Utilizing a hierarchical approach, patients were separated into different cohorts
      based on the initial analgesic prescription identified during postindex period
      with 91.7%, 34.7%, and 59.0% of the patients using opioids, NSAIDs and adjuvant
      analgesics, respectively. Multivariate regression analyses showed that patients
      with prior opioid and adjuvant analgesic use were 21% and 5% less likely to
      discontinue BTDS (P < 0.05), respectively, as compared to patients not using
      these agents. Patients with concomitant use of adjuvant analgesics were 15% less
      likely to discontinue therapy (P < 0.05) as compared to patients without
      concomitant use of these agents. Long-term BTDS persistence was also observed in
      patients who had a dose change or a last dose strength >5 mcg/hour. Sensitivity
      analyses for those with 30-day prior opioid use and patients with >= 2 claims of
      BTDS confirmed these findings. CONCLUSIONS: Prior and concomitant use of adjuvant
      analgesics, prior use of opioids, and dose adjustments were associated with
      significantly longer persistence among patients initiating BTDS. The results
      suggest that patients are less likely to discontinue BTDS early if practitioners
      account for prior treatment history and dose titration.

PMID- 24444054
TI  - Development of selective inhibitors for aldehyde dehydrogenases based on
      substituted indole-2,3-diones.
AB  - Aldehyde dehydrogenases (ALDH) participate in multiple metabolic pathways and
      have been indicated to play a role in several cancerous disease states. Our
      laboratory is interested in developing novel and selective ALDH inhibitors. We
      looked to further work recently published by developing a class of isoenzyme
      selective inhibitors using similar indole-2,3-diones that exhibit differential
      inhibition of ALDH1A1, ALDH2, and ALDH3A1. Kinetic and X-ray crystallography data
      suggest that these inhibitors are competitive against aldehyde binding, forming
      direct interactions with active-site cysteine residues. The selectivity is
      precise in that these compounds appear to interact directly with the catalytic
      nucleophile, Cys243, in ALDH3A1 but not in ALDH2. In ALDH2, the 3-keto group is
      surrounded by the adjacent Cys301/303. Surprisingly, the orientation of the
      interaction changes depending on the nature of the substitutions on the basic
      indole ring structure and correlates well with the observed structure-activity
      relationships for each ALDH isoenzyme. 

PMID- 24444056
TI  - Targeted genome editing.

PMID- 24444057
TI  - Translating human genetics into mouse: the impact of ultra-rapid in vivo genome
      editing.
AB  - Gene-targeted mutant animals, such as knockout or knockin mice, have dramatically
      improved our understanding of the functions of genes in vivo and the genetic
      diversity that characterizes health and disease. However, the generation of
      targeted mice relies on gene targeting in embryonic stem (ES) cells, which is a
      time-consuming, laborious, and expensive process. The recent groundbreaking
      development of several genome editing technologies has enabled the targeted
      alteration of almost any sequence in any cell or organism. These technologies
      have now been applied to mouse zygotes (in vivo genome editing), thereby
      providing new avenues for simple, convenient, and ultra-rapid production of
      knockout or knockin mice without the need for ES cells. Here, we review recent
      achievements in the production of gene-targeted mice by in vivo genome editing. 

PMID- 24444058
TI  - Opium as a risk factor for upper gastrointestinal cancers: a population-based
      case-control study in Iran.
AB  - BACKGROUND: Gastrointestinal cancers, including esophageal, gastric, liver and
      pancreatic are relatively common in Iran. Furthermore, consumption of opium and
      its derivatives (O&D) are considerable. This study, aimed to examine the
      association between consumption of O&D and the incidence of upper
      gastrointestinal (UGI) cancers. METHODS: In a matched case-control study in
      Kerman (located in southeast of Iran), 142 patients with UGI cancers and 284
      healthy people (matched in terms of age, sex and residence (urban/rural)) were
      recruited. Variables (using O&D, smoking, alcohol use and diet) were collected
      using a structured questionnaire. Conditional logistic regression models were
      used to assess the above mentioned association. RESULTS: Opium use was associated
      with an increased risk of UGI cancers with an adjusted OR 4.0 (95% CI=2.2-7.0). A
      very strong dose-response relation was observed between consumption of O&D and
      the incidence of UGI cancers. (Three consumption levels-none, low and high;
      OR=18.7; 95% CI=5.5-63.3). This dose-response relationship was also strong even
      in patients with gastric cancers (OR=9.2; 95% CI=2.5-33.7). CONCLUSION: The
      results of this study showed that opium consumption can be a strong risk factor
      for UGI cancers in Iran.

PMID- 24444059
TI  - NASBOD 2013: design, definitions, and metrics.
AB  - BACKGROUND: Iran has witnessed a substantial demographic and health transition,
      especially during the past 2 decades, which necessitates updated evidence-based
      policies at national and indeed at subnational scale. The National and
      Subnational Burden of Diseases, Injuries, and Risk Factors (NASBOD) Study aims to
      provide the required evidence based on updated data sources available in Iran and
      novel methods partly adopted from Global Burden of Disease 2010. OBJECTIVE: This
      paper aims at explaining the motives behind the study, the design, the
      definitions, the metrics, and the challenges due to limitations in data
      availability. METHODS: All available published and unpublished data sources will
      be used for estimating the burden of 291 diseases and 67 risk factors from 1990
      to 2013 at national and subnational scale. Published data will be extracted
      through systematic review. Existing population-based data sources include:
      registries (death and cancer), Demographic and Health Surveys, National Health
      Surveys, and other population-based surveys such as Non_Communicable Diseases
      Surveillance Surveys. Covariates will be extracted from censuses and household
      expenditure surveys. Hospital records and outpatient data will be actively
      collected as two distinct projects. Due to lack of data points by year and
      province, statistical methods will be used to impute the lacking data points
      based on determined covariates. Two main models will be used for data imputation:
      Bayesian Autoregressive Multi-level models and Spatio-Temporal regression models.
      The results from all available models will be used in an Ensemble Model to obtain
      the final estimates. Five metrics will be used for estimating the burden:
      prevalence, death, Years of Life Lost due to premature death (YLL), Years of Life
      Lost due to Disability (YLD), and Disability-Adjusted Life Years Lost (DALY).
      Burden attributable to risk factors will be estimated through comparative risk
      assessment based on Population Attributable Fraction (PAF). Uncertainty Intervals
      (UIs) will be calculated and reported for all aforementioned metrics. RESULTS: We
      will estimate trends in terms of prevalence, deaths, YLLs, YLDs, and DALYs for
      Diseases, Injuries, and Risk Factors province from 1990 to 2013. CONCLUSION:
      Results of the present study will have implications for policy making as they
      address health gaps in Iranian population and their inequality between provinces.

PMID- 24444060
TI  - Inpatient data, inevitable need for policy making at national and sub-national
      levels: a lesson learned from NASBOD.
AB  - BACKGROUND: Estimating burden of disease, injuries and risk factors is crucial
      for health policy decision making. The Burden of Diseases (BoD) studies provide
      data about the magnitude and distribution of health problems among the population
      at national and sub-national levels. The BoD studies are designed to use
      secondary data for estimating prevalence and incidence of diseases, injuries and
      risk factors. However, due to the scarcity of data sometimes it becomes
      unavoidable to collect data from medical records. Among all needed source of
      data, including surveys, registries, censuses, inpatient and outpatient data,
      hospital data are an essential source for BoD studies. Hospital Data Survey (HDS)
      aims to estimate the prevalence and incidence of diseases and injuries that led
      to admission to hospitals. This paper aims to describe the required steps for
      data gathering, sampling, analytical methods, and other needed procedures for
      HDS. STUDY DESIGN: The designed questionnaire includes demographic data, current
      health status, diseases, injuries and co-morbidities with their ICD10 codes,
      curative procedures, and treatment. A pilot study was conducted on 302 medical
      records from 6 hospitals to evaluate the validity and reliability of the
      questionnaire. Sampling frame was designed and probability proportional was used
      after being tested in the pilot study. In the next step, we will collect 367500
      medical files from 863 hospitals (0.5% of all inpatient records in hospitals
      from1996 - 2013). The HDS is the first national study in Iran that is gathering
      data through an online-offline web-based system based on electronic version of
      the questionnaire which makes the process of data cleaning and analyses more
      comfortable.

PMID- 24444061
TI  - Bayesian autoregressive multilevel modeling of burden of diseases, injuries and
      risk factors in Iran 1990 - 2013.
AB  - BACKGROUND: Statistical modeling and developing new methods for estimating burden
      of diseases, injuries and risk factors is a fundamental concern in studying the
      country health situation for better health management and policy making. Bayesian
      autoregressive multilevel model is a strong method for this kind of study though
      in complex situations it has its own challenges. Our study aims to describe the
      way of modeling space and time data through an autoregressive multilevel model
      and address challenges in complex situation. METHOD: We will obtain data from
      different published and unpublished secondary data sources including population
      based health surveys (e. g. NHS, DHS, STEP) at national and provincial levels and
      we also assess epidemiological studies via systematic review for each disease,
      injuries and risk factor over the period of 1990-2013. These data generally have
      a multilevel hierarchy and also time correlation. However, statistical analysis
      of diseases, injuries and risk factors data is primarily facing the problem of
      information scarcity. Data are generally too scarce to ensure reliable estimates
      in many practical problems. Also, there may be nonlinear changes over time,
      different kind of uncertainties in data and incompatible geographical data. We
      describe Bayesian autoregressive multilevel modeling approach that provides a
      natural solution to these problems through its ability to sensibly combine
      information from several sources of data and available prior information. In this
      hierarchy model levels of each hierarchy borrow information from each other and
      also lower levels borrow information from higher levels. We will fit the model
      using Markov Chain Monte Carlo (MCMC) methods because of its capabilities and
      benefits in complex cases. DISCUSSION: Our analyses will include different
      existing sources of data in Iran for 24 years through a rational and reasonable
      model to estimate burden of diseases, injuries and risk factors for Iran at
      national, regional and provincial levels while considering several kinds of
      uncertainties. Comprehensive and realistic estimates are always an issue of
      request that will be obtained through a suitable statistical modeling considering
      all dimensions and then can be used for making better decision in real
      situations.

PMID- 24444062
TI  - Application of spatio-temporal model to estimate burden of diseases, injuries and
      risk factors in Iran 1990 - 2013.
AB  - BACKGROUND: Identifying the burden of disease and its inequality between
      geographical regions is an important issue to study health priorities. Estimating
      burden of diseases using statistical models is inevitable especially in the
      context of rare data availability. To this purpose, the spatio-temporal model can
      provide a statistically sound approach for explaining the response variable
      observed over a region and various times. However, there are some methodological
      challenges in analysis of these complex data. Our primary objective is to provide
      some remedies to overcome these challenges. METHOD: Data from nationally
      representative surveys and systematic reviews have been gathered across
      contiguous areal units over a period of more than 20 years (1990 - 2013).
      Generally, observations of areal units are spatially and temporally correlated in
      such a way that observations closer in space and time tend to be more correlated
      than observations farther away. It is critical to determine the correlation
      structure in space-time process which has been observed over a set of irregular
      regions. Moreover, these data sets are subject to high percentage of missing,
      including misaligned areal units, areas with small sample size, and may have
      nonlinear trends over space and time. Furthermore, the Gaussian assumption might
      be overly restrictive to represent the data. In this setting, the traditional
      statistical techniques are not appropriate and more flexible and comprehensive
      methodology is required. Particularly, we focus on approaches that allow
      extending spatio-temporal models proposed previously in the literature.Since
      statistical models include both continuous and categorical outcomes, we assume a
      latent variable framework for describing the underlying structure in mixed
      outcomes and use a conditionally autoregressive (CAR) prior for the random
      effects.  In addition, we will employ misalignment modeling to combine
      incompatible areal units between data sources and/or over the years to obtain a
      unified clear picture of population health status over this period.  In order to
      take parameter uncertainties into account, we pursue a Bayesian sampling-based
      inference. Hence, a hierarchical Bayes approach is constructed to model the data.
      The hierarchical structure enables us to "borrow information" from neighboring
      areal units to improve estimates for areas with missing values and small number
      of observations. For their general applicability and ease of implementation, the
      MCMC methods are the most adapted tool to perform Bayesian inference. CONCLUSION:
      This study aims to combine different available data sources and produce precise
      and reliable evidences for Iranian burden of diseases and risk factors and their
      disparities among geographical regions over time. Providing appropriate
      statistical methods and models for analyzing the data is undoubtedly crucial to
      circumvent the problems and obtain satisfactory estimates of model parameters and
      reach accurate assessment.

PMID- 24444063
TI  - The trend of national and sub-national burden of gastrointestinal and liver
      diseases in Iran 1990 to 2013; study protocol.
AB  - BACKGROUND: It is expected that gastrointestinal (GI) and liver diseases inflict
      considerable burden on health systems in Iran; therefore, highlighting the
      significance of GI disorders across the other most burdensome diseases requires
      comprehensive assessment and regular updates of the statistics of such diseases
      in Iran. OBJECTIVE: To assess in-depth sub-national estimates and trends for the
      incidence and prevalence of selected GI and liver diseases by age, gender and
      province over the period 1990 - 2013 in Iran. METHODS: This is a national and sub
      national burden of disease study on 21 GI diseases using all available data
      sources, including cancer registry, death registration system data, hospital
      data, and all available published data. Analyses will be performed separately by
      gender, age groups, year, and province. We will conduct 21 separated systematic
      reviews of the literature for 21 diseases categories through searching online
      international electronic databases (i.e. the Medline database of the National
      Library of Medicine, Web of Science, and Scopus), Iranian search engines (i.e.,
      IranMedex, Scientific Information Database (SID), and IRANDOC), and gray
      literature. We will search the medical literature published between January 1985
      and December 2013. We generated two models, Spatio-temporal and Multilevel
      Autoregressive models, to estimate mean and uncertainty interval for the
      parameters of interest by gender, age, year, and province. The models will be
      informed by data of gender, age, year, and province. Markov Chain Monte Carlo
      (MCMC) methods will be used to perform Bayesian inference in both modeling
      framework. All programs will be written in R statistical packages (version
      3.0.1). RESULTS: We will calculate and present 1990 to 2013 trends in terms of
      prevalence, years of life lost due to premature mortality (YLLs), years lived
      with disability (YLDs), and disability-adjusted life years DALYs for the 21
      selected GI diseases by gender, and province. We will also quantify the
      uncertainty interval for the estimates of interest. CONCLUSION: Results of the
      present study will have implications for policy making; as they allow for
      understanding geographic distributions of the selected GI diseases, and
      identifying health disparities across provinces.

PMID- 24444064
TI  - National and sub-national prevalence, trend, and burden of metabolic risk factors
      (MRFs) in Iran: 1990 - 2013, study protocol.
AB  - BACKGROUND: Non-communicable diseases (NCDs) and their risk factors are the major
      public health problems. There are some documented trend and point estimations of
      metabolic risk factors for Iranian population but there are little information
      about their exposure distribution at sub-national level and no information about
      their trends and their effects on the population health.  METHODS: The present
      study protocol is aimed to provide the standard structure definitions,
      organization, data sources, methods of data gathering or generating, and data on
      trend analysis of the metabolic risk factors in NASBOD study. We will estimate
      1990 to 2013 trends of prevalence, years of life lost due to premature mortality
      (YLLs), and years lived with disability (YLDs) and disability-adjusted life years
      DALYs for MRFs by gender, age group, and province. We will also quantify the
      uncertainty interval for the estimates of interest. CONCLUSION: The findings of
      study could provide practical information regarding metabolic risk factors and
      their burden for better health policy to reduce the burden of diseases, and to
      plan cost-effective preventive strategies. The results also could be used for
      future complementary global, regional, national, and sub national studies.

PMID- 24444065
TI  - National and sub-national environmental burden of disease in Iran from 1990 to
      2013-study profile.
AB  - BACKGROUND: Development of national evidence-based public health strategies
      requires a deep understanding of the role of major risk factors (RFs) and the
      burden of disease (BOD). In this article, we explain the framework for studying
      the national and sub-national Environmental Burden of Disease (EBD) in Iran as a
      part of the National and Sub-national Burden of Disease (NASBOD) study. METHODS:
      The distribution of exposures to environmental RFs and their attributable effect
      size over 1990-2013 will be estimated through comprehensive reviews of either
      published or unpublished sources. Statistical modeling will be used to impute
      missing data in the distribution of RFs exposures for each district-year.
      National and sub-national BOD attributable to these RFs will be estimated in the
      following metrics: Prevalence, death, years of life lost due to premature death
      (YLL), years of life lost due to disability (YLD), and disability-adjusted life
      years lost (DALYs). The BOD attributable to the current distribution of exposures
      will be compared with a counterfactual exposure distribution scenario-here, the
      theoretical-minimum-risk exposure distribution. Inequalities in the distribution
      of exposure to RFs will be analyzed and manifested nationwide using geographic
      information systems. DISCUSSION: The EBD study aims to provide an official report
      to Iranian Ministry of Health and Medical Education, to publish a series of
      articles on the exposure trends of the selected environmental RFs, to estimate
      the BOD attributable to these RFs, and to assess inequalities and its
      determinants in the distribution of exposure to RFs. Iran's territory is large
      with diverse population, socioeconomic, and geographic areas. Results of this
      comparative risk assessment study may pave the way for health policy makers to
      plan more comprehensive and cost-effective evidence-based strategies.

PMID- 24444066
TI  - National and sub-national prevalence, trend, and burden of cardiometabolic risk
      factors in Iranian children and adolescents, 1990 - 2013.
AB  - BACKGROUND: Non-communicable diseases (NCDs) and their risk factors are a major
      health threat at the global level, notably for developing countries. The tracking
      of cardiometabolic risk factors from childhood to adulthood is well documented.
      Therefore, more attention needs to be directed at primordial and primary
      prevention of NCDs. Given the high prevalence of NCDs and their risk factors in
      Iranian population, a study was designed to determine the attributable burden of
      cardiometabolic risk factors in Iranian pediatric population during past decades.
      METHODS: This paper explains the definitions, organization, data sources, methods
      of data gathering or generating, data analyses, and the trend analysis of the
      study. A national expert working group addressed unmet needs and offered
      consultations on the selection of risk factors and the practical definition of
      disease. In the later stages, during the course of the study, they will supervise
      the statistical modeling methods, the interpretation of results, and the
      publication strategy. Also an international expert advisory group will
      collaborate with the project team. CONCLUSION: The findings of this study could
      provide basic information regarding NCD related risk factors, and their burden
      and trends in children, which is necessary for health policy decisions to reduce
      the burden of disease and to plan cost-effective preventive strategies.

PMID- 24444068
TI  - A rare presentation of pulmonary sarcoidosis with massive hemoptysis.
AB  - Sarcoidosis is a multisystem disorder with unknown etiology and is characterized
      by noncaseating granuloma in involved organs. Sarcoidosis frequency involves the
      lungs. Common presenting symptoms include cough, dyspnea and chest pain. Massive
      hemoptysis is a rare presentation in sarcoidosis. There are a few reports on
      massive hemoptysis in sarcoidosis. We are reporting the case of a 24 year old man
      who presented with massive hemoptysis and normal lung parenchyma. The diagnosis
      was made with mediastinal lymph node biopsy. 

PMID- 24444067
TI  - Establishing a liver transplantation program at Tehran University of Medical
      Sciences, Iran: a report of ten years of experience.
AB  - In 2001, a Liver Transplantation (LT) program was commenced in Imam Khomeini
      Hospital Complex as the first one in the capital city of Tehran which is the
      second liver transplantation center in Iran. This study presents the results of
      our 10-year experience with LT. 

PMID- 24444069
TI  - Left anterior descending coronary artery dissection after blunt chest trauma.
AB  - Coronary artery dissection is a well-known albeit unusual complication of blunt
      chest trauma. It is also an uncommon cause of myocardial infarction. Only a few
      such cases have been reported, probably due to the high rate of sudden death. We
      report a case of left anterior descending (LAD) coronary artery dissection in a
      healthy 38-year-old female caused by blunt chest trauma. The patient was referred
      to our hospital with a complaint of chest pain. Electrocardiography showed T-wave
      inversion, echocardiography a revealed circumferential pericardial effusion, and
      the coronary angiogram demonstrated a thrombotic dissection of the LAD.  Troponin
      I was the only biomarker with elevated level. CT coronary angiography was
      performed using the subtotal occlusion of the LAD and illustrated a relatively
      good LAD run-off, and thallium scintigraphy displayed viable myocardium in this
      territory. Despite the total occlusion of the LAD in our case, myocardial injury
      was not significant due to the relatively good LAD run-off. She underwent
      coronary artery bypass graft surgery with an excellent result. 

PMID- 24444070
TI  - Traumatic ulcerative granuloma with stromal eosinophilia.
AB  - Chronic ulcers of the oral mucosa are the lesions which a physician comes across
      frequently. "Eosinophilic Ulcer" is a rare variety of that. Eosinophilic ulcer or
      traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a chronic
      benign lesion of the oral mucosa and is a relatively recent delineated entity.
      Its etiopathogenesis is still uncertain but trauma seems to play a fundamental
      role. Clinically the lesion manifests as an isolated ulcer, showing a raised and
      indurated border in addition to a white or yellowish bed. Microscopically, it is
      characterized by diffuse polymorphic inflammatory infiltrate, rich in
      eosinophils, involving the superficial mucosa and the deeper muscle layer with
      epitheliod cells. Hereby, reporting a case of a 60-year-old female patient who
      presented with a chief complaint of non-healing painful ulcer on the tongue. 

PMID- 24444071
TI  - Posterior mediastinal cyst.
AB  - Hydatid disease is still an important health problem in the world. Mediastinal
      localization of hydatidosis is very rare. We report the case of a 19-year-old man
      who presented with right chest wall pain and cough. Chest X-Ray and computed
      tomography showed a mediastinal cystic mass. A right posterolateral thoracotomy
      was performed and the cystic mass was identified. Daughter cysts were seen within
      the cyst when the lesion was accidentally opened during the procedure. Cyst mass
      was radically resected. No complication or recurrence was seen in the follow-up
      period. 

PMID- 24444072
TI  - Photoclinic.

PMID- 24444073
TI  - Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord
      mesenchymal stem cells in nude mice.
AB  - BACKGROUND: The human umbilical cord mesenchymal stem cells (hUCMSCs) have the
      ability to migrate into tumors and therefore have been considered as an
      alternative source of mesenchymal progenitors for the therapy of malignant
      diseases. The present study was aimed to investigate effect of hUCMSCs as
      vehicles for a constant source of transgenic interleukin-21 (IL-21) on ovarian
      cancer in vivo. METHODS: The hUCMSCs were engineered to express IL-21 via
      lentiviral vector- designated 'hUCMSCs-LV-IL-21', and then were transplanted into
      SKOV3 ovarian cancer xenograft-bearing nude mice. The therapeutic efficacy and
      mechanisms of this procedure on ovarian cancer was evaluated. RESULTS: The
      isolated hUCMSCs were induced to differentiate efficiently into osteoblast and
      adipocyte lineages in vitro. The expressed IL-21 in the supernatant from hUCMSCs
      LV-IL-21 obviously stimulated splenocyte's proliferation. The hUCMSCs-LV-IL-21
      significantly reduced SKOV3 ovarian cancer burden in mice indicated by tumor
      sizes compared with control mice. The expressed IL-21 not only regulated the
      levels of IFN-gamma and TNF-alpha in the mouse serum but also increased the
      expression of NKG2D and MIC A molecules in the tumor tissues. The down regulation
      of beta-catenin and cyclin-D1 in the tumor tissues may refer to the inhibition of
      SKOV3 ovarian cancer growth in mice. In addition, hUCMSCs did not form gross or
      histological teratomas up to 60 days posttransplantation in murine lung, liver,
      stomach and spleen. CONCLUSION: These results clearly indicate a safety and
      usability of hUCMSCs-LV- IL-21 in ovarian cancer gene therapy, suggesting the
      strategy may be a promising new method for clinical treatment of ovarian cancer.

PMID- 24444074
TI  - Design and synthesis of a new class of 4-aminoquinolinyl- and 9-anilinoacridinyl
      Schiff base hydrazones as potent antimalarial agents.
AB  - A series of novel 4-aminoquinolinyl and 9-anilinoacridinyl Schiff base hydrazones
      have been synthesized and evaluated for their antimalarial activity. All
      compounds were evaluated in vitro for their antimalarial activity against
      chloroquine-sensitive strain 3D7 and the chloroquine-resistant K1 strain of
      Plasmodium falciparum and for cytotoxicity toward Vero cells. Compounds 17, 20,
      and 21 displayed good activity against the 3D7 strain with IC50 values ranging
      from 19.69 to 25.38 nm. Moreover, compounds 16, 17, 21, 24, 32, and 33 exhibited
      excellent activities (21.64-54.26 nm) against K1 strain and several compounds
      displayed beta-hematin inhibitory activity, suggesting that they act on the heme
      crystallization process such as CQ. Compounds were also found to be non-toxic
      with good selectivity index. 

PMID- 24444075
TI  - Regulation of epinasty induced by 2,4-dichlorophenoxyacetic acid in pea and
      Arabidopsis plants.
AB  - The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) causes uncontrolled cell
      division and malformed growth in plants, giving rise to leaf epinasty and stem
      curvature. In this study, mechanisms involved in the regulation of leaf epinasty
      induced by 2,4-D were studied using different chemicals involved in reactive
      oxygen species (ROS) accumulation (diphenyleniodonium, butylated hydroxyanisole,
      EDTA, allopurinol), calcium channels (LaCl3), protein phosphorylation
      (cantharidin, wortmannin) and ethylene emission/perception (aminoethoxyvinyl
      glycine, AgNO3). The effect of these compounds on the epinasty induced by 2,4-D
      was analysed in shoots and leaf strips from pea plants. For further insight into
      the effect of 2,4-D, studies were also made in Arabidopsis mutants deficient in
      ROS production (rbohD, rbohF, xdh), ethylene (ein 3-1, ctr 1-1, etr 1-1),
      abscisic acid (aba 3.1), and jasmonic acid (coi 1.1, jar 1.1, opr 3) pathways.
      The results suggest that ROS production, mainly .OH, is essential in the
      development of epinasty triggered by 2,4-D. Epinasty was also found to be
      regulated by Ca2+, protein phosphorylation and ethylene, although all these
      factors act downstream of ROS production. The use of Arabidopsis mutants appears
      to indicate that abscisic and jasmonic acid are not involved in regulating
      epinasty, although they could be involved in other symptoms induced by 2,4-D.

PMID- 24444076
TI  - Neurite outgrowth on electrospun nanofibers with uniaxial alignment: the effects
      of fiber density, surface coating, and supporting substrate.
AB  - Electrospun nanofibers with uniaxial alignment have recently gained its
      popularity as scaffolds for neural tissue engineering. Many studies have
      demonstrated that the nanofibers could guide the neurites to extend along the
      direction of alignment, resembling the native hierarchy of the nerve tissue.
      However, the contact cues provided by the nanofibers can be far more complicated
      than just guiding the neurites to extend along them. In the current study, we
      used dorsal root ganglia as a model system to systematically investigate the
      interactions between neurites and uniaxially aligned nanofibers. We demonstrated,
      for the first time, that the neurites could not only project along the
      nanofibers, but also be directed to grow along a direction perpendicular to the
      aligned nanofibers, depending on the following parameters: (i) the density of
      nanofibers, (ii) the protein deposited on the surfaces of the nanofibers, and
      (iii) surface properties of the substrate on which the nanofibers were supported.
      We also investigated the pharmacological effect of myosin II inhibition on the
      nanofiber-guided growth of neurites by adding blebbistatin to the culture medium.
      Our findings offer new insights into the design of nanofiber-based scaffolds for
      nerve injury repair and will provide new guidelines for the construction of well
      defined neuronal network architecture (the so-called neural circuits). 

PMID- 24444077
TI  - Unusual combined thymic mucoepidermoid carcinoma and thymoma: a case report and
      review of literature.
AB  - BACKGROUND: In rare condition, combined thymic epithelial tumors showing either
      type A or type B thymomas areas combined with thymic carcinoma components may
      occur in thymus. Mucoepidermoid carcinoma (MEC) of the thymus is rare in thymic
      carcinoma, and so far there is no report to describe a combined epithelial tumor
      of thymus with MEC component. We report an unusual case of combined thymic
      MEC/type B2 thymoma in a middle-aged male occurring in a mass of anterior
      mediastinum. CASE REPORT: A 51-year-old Chinese male patient presented with a 6
      month history of right ptosis and progressive muscle weakness. Computed
      tomography (CT) examination revealed a solitary, well-circumscribed mass was in
      the anterior mediastinum with mild heterogeneous enhancement. Histologically, the
      mass contained two separated components and displayed typically histological
      features of low-grade MEC and type B2 thymoma, respectively. There was no gradual
      transition of these two components observed in mass, and no enlarged lymph node
      was found in the surrounding tissues. A diagnosis of combined thymic MEC/type B2
      thymoma was made. The patient received thymectomy to resect the mass totally.
      After surgery, chemotherapy with regiments of cisplatin and mitomycin, and
      radiotherapy of the main tumor bed were performed on the patient. There was no
      evidence of tumor recurrence during the period of 12 months follow-up.
      CONCLUSION: To our best knowledge, this is the first report of combined thymic
      epithelial tumor with MEC component. Although this tumor is rare, the diagnosis
      of a thymic MEC should be taken into consideration when a combined epithelial
      tumor is occasionally encountered in thymus. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/9721397571157894.

PMID- 24444079
TI  - Different approaches for obtaining antibodies from human B cells.
AB  - Antibodies have emerged as powerful therapeutics effective for treating a number
      of human conditions and diseases. While early successes utilized small animals to
      generate therapeutic antibodies, human antibodies are now preferred in order to
      limit anti-antibody immune responses. Antibodies with human amino acid sequences
      can be generated in a number of ways, such as humanizing antibodies from other
      species or expressing human antibodies in transgenic animals. This review focuses
      on methods for obtaining antibodies directly from human B cells. These methods
      use both antigen exposed and non-exposed ("naive") humans as B cell sources, and
      apply various technologies to isolate desired antibodies; including cell line
      generation, single cell isolation, display technologies, and B cell library
      generation. 

PMID- 24444078
TI  - A microfluidic-enabled mechanical microcompressor for the immobilization of live
      single- and multi-cellular specimens.
AB  - A microcompressor is a precision mechanical device that flattens and immobilizes
      living cells and small organisms for optical microscopy, allowing enhanced
      visualization of sub-cellular structures and organelles. We have developed an
      easily fabricated device, which can be equipped with microfluidics, permitting
      the addition of media or chemicals during observation. This device can be used on
      both upright and inverted microscopes. The apparatus permits micrometer precision
      flattening for nondestructive immobilization of specimens as small as a
      bacterium, while also accommodating larger specimens, such as Caenorhabditis
      elegans, for long-term observations. The compressor mount is removable and allows
      easy specimen addition and recovery for later observation. Several customized
      specimen beds can be incorporated into the base. To demonstrate the capabilities
      of the device, we have imaged numerous cellular events in several protozoan
      species, in yeast cells, and in Drosophila melanogaster embryos. We have been
      able to document previously unreported events, and also perform photobleaching
      experiments, in conjugating Tetrahymena thermophila. 

PMID- 24444081
TI  - Ubiquitin-like prokaryotic MoaD as a fusion tag for expression of heterologous
      proteins in Escherichia coli.
AB  - BACKGROUND: Eukaryotic ubiquitin and SUMO are frequently used as tags to enhance
      the fusion protein expression in microbial host. They increase the solubility and
      stability, and protect the peptides from proteolytic degradation due to their
      stable and highly conserved structures. Few of prokaryotic ubiquitin-like
      proteins was used as fusion tags except ThiS, which enhances the fusion
      expression, however, reduces the solubility and stability of the expressed
      peptides in E. coli. Hence, we investigated if MoaD, a conserved small sulfur
      carrier in prokaryotes with the similar structure of ubiquitin, could also be
      used as fusion tag in heterologous expression in E. coli. RESULTS: Fusion of MoaD
      to either end of EGFP enhanced the expression yield of EGFP with a similar
      efficacy of ThiS. However, the major parts of the fusion proteins were expressed
      in the aggregated form, which was associated with the retarded folding of EGFP,
      similar to ThiS fusions. Fusion of MoaD to insulin chain A or B did not boost
      their expression as efficiently as ThiS tag did, probably due to a less efficient
      aggregation of products. Interestingly, fusion of MoaD to the murine ribonuclease
      inhibitor enhanced protein expression by completely protecting the protein from
      intracellular degradation in contrast to ThiS fusion, which enhanced degradation
      of this unstable protein when expressed in E. coli. CONCLUSIONS: Prokaryotic
      ubiquitin-like protein MoaD can act as a fusion tag to promote the fusion
      expression with varying mechanisms, which enriches the arsenal of fusion tags in
      the category of insoluble expression.

PMID- 24444080
TI  - Host biomarkers distinguish dengue from leptospirosis in Colombia: a case-control
      study.
AB  - BACKGROUND: Dengue fever and leptospirosis have partially overlapping geographic
      distributions, similar clinical presentations and potentially life-threatening
      complications but require different treatments. Distinguishing between these
      cosmopolitan emerging pathogens represents a diagnostic dilemma of global
      importance. We hypothesized that perturbations in host biomarkers can
      differentiate between individuals with dengue fever and leptospirosis during the
      acute phase of illness. METHODS: We randomly selected subjects from a prospective
      cohort study of acute febrile illness in Bucaramanga, Colombia and tested 19
      serum biomarkers by ELISA in dengue fever (DF, n = 113) compared to subjects with
      leptospirosis (n = 47). Biomarkers were selected for further analysis if they had
      good discriminatory ability (area under the ROC curve (AUC) >0.80) and were
      beyond a reference range (assessed using local healthy controls). RESULTS: Nine
      biomarkers differed significantly between dengue fever and leptospirosis, with
      higher levels of Angptl3, IL-18BP, IP-10/CXCL10, Platelet Factor 4, sICAM-1,
      Factor D, sEng and sKDR in dengue and higher levels of sTie-2 in leptospirosis (p
      < 0.001 for all comparisons). Two biomarkers, sEng and IL18BP, showed excellent
      discriminatory ability (AUROC >0.90). When incorporated into multivariable
      models, sEng and IL18BP improved the diagnostic accuracy of clinical information
      alone. CONCLUSIONS: These results suggest that host biomarkers may have utility
      in differentiating between dengue and leptospirosis, clinically similar
      conditions of different etiology.

PMID- 24444082
TI  - High-throughput SNP discovery in the rabbit (Oryctolagus cuniculus) genome by
      next-generation semiconductor-based sequencing.
AB  - The European rabbit (Oryctolagus cuniculus) is a domesticated species with one of
      the broadest ranges of economic and scientific applications and fields of
      investigation. Rabbit genome information and assembly are available (oryCun2.0),
      but so far few studies have investigated its variability, and massive discovery
      of polymorphisms has not been published yet for this species. Here, we sequenced
      two reduced representation libraries (RRLs) to identify single nucleotide
      polymorphisms (SNPs) in the rabbit genome. Genomic DNA of 10 rabbits belonging to
      different breeds was pooled and digested with two restriction enzymes (HaeIII and
      RsaI) to create two RRLs which were sequenced using the Ion Torrent Personal
      Genome Machine. The two RRLs produced 2 917 879 and 4 046 871 reads, for a total
      of 280.51 Mb (248.49 Mb with quality >20) and 417.28 Mb (360.89 Mb with quality
      >20) respectively of sequenced DNA. About 90% and 91% respectively of the
      obtained reads were mapped on the rabbit genome, covering a total of 15.82% of
      the oryCun2.0 genome version. The mapping and ad hoc filtering procedures allowed
      to reliably call 62 491 SNPs. SNPs in a few genomic regions were validated by
      Sanger sequencing. The Variant Effect Predictor Web tool was used to map SNPs on
      the current version of the rabbit genome. The obtained results will be useful for
      many applied and basic research programs for this species and will contribute to
      the development of cost-effective solutions for high-throughput SNP genotyping in
      the rabbit.

PMID- 24444083
TI  - Cryptic differences in colour among Mullerian mimics: how can the visual
      capacities of predators and prey shape the evolution of wing colours?
AB  - Antagonistic interactions between predators and prey often lead to co-evolution.
      In the case of toxic prey, aposematic colours act as warning signals for
      predators and play a protective role. Evolutionary convergence in colour patterns
      among toxic prey evolves due to positive density-dependent selection and the
      benefits of mutual resemblance in spreading the mortality cost of educating
      predators over a larger prey assemblage. Comimetic species evolve highly similar
      colour patterns, but such convergence may interfere with intraspecific signalling
      and recognition in the prey community, especially for species involved in
      polymorphic mimicry. Using spectrophotometry measures, we investigated the
      variation in wing coloration among comimetic butterflies from distantly related
      lineages. We focused on seven morphs of the polymorphic species Heliconius numata
      and the seven corresponding comimetic species from the genus Melinaea.
      Significant differences in the yellow, orange and black patches of the wing were
      detected between genera. Perceptions of these cryptic differences by bird and
      butterfly observers were then estimated using models of animal vision based on
      physiological data. Our results showed that the most strikingly perceived
      differences were obtained for the contrast of yellow against a black background.
      The capacity to discriminate between comimetic genera based on this colour
      contrast was also evaluated to be higher for butterflies than for birds,
      suggesting that this variation in colour, likely undetectable to birds, might be
      used by butterflies for distinguishing mating partners without losing the
      benefits of mimicry. The evolution of wing colour in mimetic butterflies might
      thus be shaped by the opposite selective pressures exerted by predation and
      species recognition.

PMID- 24444084
TI  - A changing treatment landscape for multiple sclerosis: challenges and
      opportunities.
AB  - Multiple sclerosis (MS) is primarily an autoimmune disease of the central nervous
      system, but also encompasses prominent neurodegenerative aspects. A significant
      proportion of MS patients will develop neurological disability over time and up
      until recently treatment options have been limited. However, MS treatment is now
      at a stage of rapid progress, with several new drugs that have reached the market
      or will be launched in the near future. This provides new opportunities for
      individualized treatment, but also creates new challenges regarding monitoring of
      disease activity, long-term safety issues and efficacy, not least in patients
      with progressive disease.

PMID- 24444085
TI  - Association between the g.14461A>G genetic polymorphism of the TLR4 gene and type
      2 diabetes mellitus risk in a Chinese population.
AB  - OBJECTIVE: Toll-like receptor 4 (TLR4) is an important candidate gene for
      mediating the susceptibility to type 2 diabetes mellitus (T2DM). The purpose of
      this study was to investigate the association between the TLR4 gene polymorphisms
      and T2DM susceptibility. METHODS: A total of 671 T2DM patients and 677 healthy
      controls were recruited in this study. The created restriction site-polymerase
      chain reaction and DNA sequencing methods have been used to analyze the TLR4 gene
      polymorphisms. RESULTS: One novel genetic polymorphism (g.14461A>G) was found.
      Our data indicated that the g.14461A>G genetic polymorphism was significantly
      associated with the increased susceptibility to T2DM in a homozygote comparison
      (GG vs. AA: odds ratio [OR]=2.09, 95% confidence interval [CI] 1.44-3.04,
      p<0.001), dominant model (GG/AG vs. AA: OR=1.27, 95% CI 1.03-1.57, p=0.028),
      recessive model (GG vs. AG/AA: OR=1.98, 95% CI 1.39-2.83, p<0.001), and allele
      contrast (G vs. A: OR=1.33, 95% CI 1.13-1.57, p=0.001). The allele-G might be the
      risk allele for enhancing the susceptibility to T2DM. CONCLUSION: These
      preliminary findings suggest that the g.14461A>G genetic polymorphism of the TLR4
      gene is potentially related to the susceptibility to T2DM in the studied
      population.

PMID- 24444086
TI  - Lanthanide loading of luminescent multi-tridentate polymers under thermodynamic
      control.
AB  - This work illustrates the use of basic statistical mechanics for rationalizing
      the loading of linear multitridentate polymers with trivalent lanthanides,
      Ln(III), and identifies the specific ionic sizes of europium and yttrium as
      promising candidates for the further design of organized heterometallic f-f'
      materials. Using [Ln(hfac)3] (hfac = hexafluoroacetylacetonate) as lanthanide
      carriers, the thermodynamically controlled formation of Wolf type-II
      lanthanidopolymers [{Ln(hfac)3}m(L4)] is modeled with the help of two simple
      microscopic descriptors: (i) the intrinsic affinity of Ln(III) for the tridentate
      binding sites fN3(Ln) and (ii) the intermetallic interactions DeltaE1-2(Ln,Ln)
      operating between two occupied adjacent sites. Selective complexation (fN3La <<
      fN3Eu > fN3(Y)) modulated by anticooperative interactions (DeltaE1-2(La,La) ?
      DeltaE1-2(Eu,Eu) > DeltaE1-2(Y,Y) ~ 0) favors the fixation of Eu(III) in
      semiorganized lanthanidopolymers [{Eu(hfac)3}m(L4)] displaying exploitable light
      downshifting.

PMID- 24444087
TI  - Submucosal tunneling endoscopic resection for simultaneous esophageal and cardia
      submucosal tumors originating from the muscularis propria layer (with video).
AB  - Submucosal tunneling endoscopic resection (STER) is a new treatment technique for
      upper gastrointestinal submucosal tumors (SMT) originating from the muscularis
      propria (MP) layer. In contrast to conventional endoscopic resection, the new
      therapy can maintain the mucosal integrity of the digestive tract, which
      effectively prevents mediastinitis and peritonitis. STER, although a known
      method, has not been widely adopted because of technical difficulties. Here, we
      describe the case of a 30-year-old patient presenting with two separate SMT
      originating from the esophageal and cardia MP layer. A 2-cm longitudinal mucosal
      incision was made approximately 5 cm proximal to the esophageal SMT, and the
      esophageal and cardia SMT were dissected successively in the same submucosal
      tunnel. In the relevant literature, this is the first case of STER for resecting
      esophageal and cardia SMT using the same submucosal tunnel. 

PMID- 24444088
TI  - The 14th International Conference on Alzheimer's Drug Discovery, 9 - 10 September
      2013, in Jersey City, New Jersey.
AB  - The following conference was the 14th International Conference on Alzheimer's
      Drug Discovery held 9 - 10 September 2013, in Jersey City, NJ. The conference
      attracted about 140 attendees with 49% from academia, 36% from industry and
      private practice, 10% from nonprofit organizations and 2% from the government.
      The meeting had two plenary speakers that kicked off each morning of the
      conference and then two sessions each day to cover different aspects of
      Alzheimer's disease drug discovery. There were sessions on neuroprotection,
      mitochondrial function, biomarkers, ApoE, tau and protein clearance. The
      conference was organized by the Alzheimer's Drug Discovery Foundation (ADDF) with
      all of the presenters supported by grants awarded by the ADDF. The conference had
      financial support from the pharmaceutical companies Merck & Co., Eli Lilly & Co.
      and Pfizer, Inc. Friends, exhibitors and media partners also helped financially
      support the conference. 

PMID- 24444090
TI  - Fabrication of micro-ridge long-period gratings inscribed on polarization
      maintaining fibers.
AB  - We experimentally investigated a simple and new technique for the fabrication of
      micro-ridge long-period gratings (MRLPGs) based on polarization-maintaining
      fibers (PMFs). The cladding region of the PMFs was etched periodically using a
      wet etching technique resulting in the periodic formation of micro-ridges on the
      surface of the PMF. The PMF-based MRLPGs has two resonant peaks because of the
      birefringence of the PMF. The extinction ratios of two resonant peaks of the PMF
      based MRLPGs were effectively improved by increasing the applied strain because
      of the photoelastic effect. 

PMID- 24444092
TI  - Metallacycle-catalyzed SNAr reaction in water: supramolecular inhibition by means
      of host-guest complexation.
AB  - The performance of a Pt(II) diazapyrenium-based metallacycle as a reusable
      substoichiometric catalyst for the SNAr reaction between halodinitrobenzenes and
      sodium azide at rt in aqueous media is reported. The results suggest that the
      catalytic effect is promoted by the association of the azide to the diazapyrenium
      cationic subunits of the catalyst. The findings demonstrate that the formation of
      an inclusion complex between pyrene and the metallacycle has a regulatory effect
      over the system, resulting in allosteric-like inhibition of the SNAr reaction.

PMID- 24444091
TI  - Environment sensing in spring-dispersed seeds of a winter annual Arabidopsis
      influences the regulation of dormancy to align germination potential with
      seasonal changes.
AB  - Seed dormancy cycling plays a crucial role in the lifecycle timing of many
      plants. Little is known of how the seeds respond to the soil seed bank
      environment following dispersal in spring into the short-term seed bank before
      seedling emergence in autumn. Seeds of the winter annual Arabidopsis ecotype Cvi
      were buried in field soils in spring and recovered monthly until autumn and their
      molecular eco-physiological responses were recorded. DOG1 expression is initially
      low and then increases as dormancy increases. MFT expression is negatively
      correlated with germination potential. Abscisic acid (ABA) and gibberellin (GA)
      signalling responds rapidly following burial and adjusts to the seasonal change
      in soil temperature. Collectively these changes align germination potential with
      the optimum climate space for seedling emergence. Seeds naturally dispersed to
      the soil in spring enter a shallow dormancy cycle dominated by spatial sensing
      that adjusts germination potential to the maximum when soil environment is most
      favourable for germination and seedling emergence upon soil disturbance. This
      behaviour differs subtly from that of seeds overwintered in the soil seed bank to
      spread the period of potential germination in the seed population (existing seed
      bank and newly dispersed). As soil temperature declines in autumn, deep dormancy
      is re-imposed as seeds become part of the persistent seed bank. 

PMID- 24444093
TI  - ABO blood type and stroke risk: the REasons for Geographic And Racial Differences
      in Stroke Study.
AB  - BACKGROUND: ABO blood type is an inherited trait associated with coagulation
      factor levels and vascular outcomes. OBJECTIVES: To assess the association of
      blood type with stroke and whether blood type contributes to racial disparities
      in stroke in the United States. PATIENTS AND METHODS: The REasons for Geographic
      And Racial Differences in Stroke (REGARDS) Study recruited 30 239 participants
      between 2003 and 2007. Using a case-cohort design, blood type was genotyped in
      646 participants with stroke and a 1104-participant cohort random sample. Cox
      models that adjusted for Framingham stroke risk factors were used to assess the
      association of blood type with stroke. RESULTS: During 5.8 years of follow-up,
      blood types A or B vs. type O were not associated with stroke. Blood type AB vs.
      O was associated with an increased risk of stroke (adjusted hazard ratio [HR]
      1.83, 95% confidence interval [CI] 1.01-3.30). The association of blood type AB
      vs. O was greater in those without diabetes (adjusted HR 3.33, 95% CI 1.61-6.88)
      than those with diabetes (adjusted HR 0.49, 95% CI 0.17-1.44) (P interaction =
      0.02). Factor VIII levels accounted for 60% (95% CI 11%-98%) of the association
      of AB blood type and stroke risk. CONCLUSION: Blood type AB is associated with an
      increased risk of stroke that is not attenuated by conventional stroke risk
      factors, and factor VIII levels were associated with 60% of the association.
      While blood type AB is rare in the US population, it is a significant stroke risk
      factor and may play an important role in stroke risk in these individuals.

PMID- 24444094
TI  - Exchange protein activated by cyclic AMP is involved in the regulation of
      adipogenic genes during 3T3-L1 fibroblasts differentiation.
AB  - Adipogenesis is stimulated in 3T3-L1 fibroblasts by a combination of insulin,
      dexamethasone and isobutylmethylxanthine, IBMX, (I+D+M). Two transcription
      factors are important for the acquisition of the adipocyte phenotype, C/EBP beta
      (CCAT enhancer-binding protein beta) and PPAR gamma (peroxisome proliferator
      activated receptor gamma). IBMX increases cAMP content, which can activate
      protein kinase A (PKA) and/or EPAC (exchange protein activated by cAMP). To
      investigate the importance of IBMX in the differentiation mixture, we first
      evaluated the effect of the addition of IBMX on the increase of C/EBP beta and
      PPAR gamma and found an enhancement of the amount of both proteins. IBMX addition
      (I+D+M) or its replacement with a cAMP analogue, dibutyryl-cAMP or 8-(4
      chlorophenylthio)-2-O'-methyl-cAMP (8CPT-2-Me-cAMP), the latter activates EPAC
      and not PKA, remarkably increased PPAR gamma mRNA. However, neither I+D nor any
      of the inducers alone, increased PPAR gamma mRNA to a similar extent, suggesting
      the importance of the presence of both IBMX and I+D. It was also found that the
      addition of IBMX or 8CPT-2-Me-cAMP was able to increase the content of C/EBP beta
      with respect to I+D. In agreement with these findings, a microarray analysis
      showed that the presence of either 8CPT-2-Me-cAMP or IBMX in the differentiation
      mixture was able to upregulate PPAR gamma and PPAR gamma-activated genes as well
      as other genes involved in lipid metabolism. Our results prove the involvement of
      IBMX-cAMP-EPAC in the regulation of adipogenic genes during differentiation of
      3T3-L1 fibroblasts and therfore contributes to elucidate the role of cyclic AMP
      in this process. 

PMID- 24444095
TI  - Risk miRNA screening of ovarian cancer based on miRNA functional synergistic
      network.
AB  - BACKGROUND: miRNAs are proved to have causal roles in tumorgenesis involving
      various types of human cancers, but the mechanism is not clear. We aimed to
      explore the effect of miRNAs on the development of ovarian cancer and the
      underlying mechanism. METHODS: The miRNA expression profile GSE31801 was
      downloaded from GEO (Gene Expression Omnibus) database. Firstly, the
      differentially expressed miRNAs were screened. Target genes of the miRNAs were
      collected from TargetScan, PicTar, miRanda, and DIANA-microT database, then the
      miRNA-miRNA co-regulating network was constructed using miRNA pairs with common
      regulated target genes. Next, the functional modules in the network were studied,
      the miRNA pairs regulated at least one modules were enriched to form the miRNA
      functional synergistic network (MFSN). RESULTS: Risk miRNA were selected in MFSN
      according to the topological structure. Transcript factors (TFs) in MFSN were
      identified, followed by the miRNA-transcript factor networks construction.
      Totally, 42 up- and 61 down-regulated differentially expressed miRNAs were
      identified, of which 68 formed 2292 miRNA pairs in the miRNA-miRNA co-regulating
      network. GO: 0007268 (synaptic transmission) and GO: 0019226 (transmission of
      nerve impulse) were the two common functions of miRNAs in MFSN, and hsa-miR-579
      (36), hsa-miR-942 (31), hsa-miR-105 (31), hsa-miR-150 (34), and hsa-miR-27a* (32)
      were selected as the hub nodes in MFSN. CONCLUSIONS: In all, 17 TFs, including
      CREM, ERG, and CREB1 were screened as the cancer related TFs in MFSN. Other TFs,
      such as BIN1, FOXN3, FOXK1, FOXP2, and ESRRG with high degrees may be inhibited
      in ovarian cancer. MFSN gave us a new shed light on the mechanism studies in
      ovarian cancer.

PMID- 24444096
TI  - Discovering symptom co-occurrence patterns from 604 cases of depressive patient
      data using latent tree models.
AB  - OBJECTIVES: In order to treat depressive patients using Traditional Chinese
      Medicine (TCM), it is necessary to classify them into subtypes from the TCM
      perspective. Those subtypes are called Zheng types. This article aims at
      providing evidence for the classification task by discovering symptom co
      occurrence patterns from clinic data. METHODS: Six hundred four (604) cases of
      depressive patient data were collected. The subjects were selected using the
      Chinese classification of mental disorder clinic guideline CCMD-3. The symptoms
      were selected based on the TCM literature on depression. The data were analyzed
      using latent tree models (LTMs). RESULTS: An LTM with 29 latent variables was
      obtained. Each latent variable represents a partition of the subjects into 2 or
      more clusters. Some of the clusters capture probabilistic symptom co-occurrence
      patterns, while others capture symptom mutual-exclusion patterns. Most of the co
      occurrence patterns have clear TCM Zheng connotations. CONCLUSIONS: From clinic
      data about depression, probabilistic symptom co-occurrence patterns have been
      discovered that can be used as evidence for the task of classifying depressive
      patients into Zheng types.

PMID- 24444097
TI  - Independent influence of negative blood cultures and bloodstream infections on in
      hospital mortality.
AB  - BACKGROUND: The independent influence of blood culture testing and bloodstream
      infection (BSI) on hospital mortality is unclear. METHODS: We included all adults
      treated in non-psychiatric services at our hospital between 2004 and 2011. We
      identified all blood cultures and their results to determine the independent
      association of blood culture testing and BSI on death in hospital using
      proportional hazards modeling that adjusted for important covariates. RESULTS: Of
      297 070 hospitalizations, 48 423 had negative blood cultures and 5274 had BSI. 12
      529 (4.2%) died in hospital. Compared to those without blood cultures, culture
      negative patients and those with BSI were sicker. Culture-negative patients had a
      significantly increased risk of death in hospital (adjusted hazard ratio [HR]
      ranging between 3.1 and 4.4 depending on admission urgency, extent of
      comorbidities, and whether the blood culture was taken in the intensive care
      unit). Patients with BSI had a significantly increased risk of death (adj-HR
      ranging between 3.8 and 24.3] that was significantly higher when BSI was:
      diagnosed within the first hospital day; polymicrobial; in patients who were
      exposed to immunosuppressants or were neutropenic; or due to Clostridial and
      Candidal organisms. Death risk in culture negative and bloodstream infection
      patients decreased significantly with time. CONCLUSIONS: Risk of death in
      hospital is independently increased both in patients with negative blood cultures
      and further in those with bloodstream infection. Death risk associated with
      bloodstream infections varied by the patient's immune status and the causative
      microorganism.

PMID- 24444098
TI  - Is there a benefit to postoperative fluid restriction following infant surgery?
AB  - OBJECTIVE: Fluid restriction is often employed immediately following cardiac
      surgery in children. The goal of this approach is to achieve an early negative
      fluid balance, which theoretically should lead to less interstitial edema and
      earlier extubation. The purpose of this study was to determine whether time to
      negative fluid balance in infants after undergoing systemic-to-pulmonary artery
      shunt palliation impacts duration of mechanical ventilation and hospital length
      of stay. DESIGN: This is a retrospective study of neonates who underwent a
      modified systemic-to-pulmonary artery shunt at a single institution. SETTING:
      University hospital pediatric cardiac intensive care unit (CICU). PATIENTS:
      Neonates who underwent a modified systemic-to-pulmonary artery shunt between
      January 1, 2009 and June 1, 2011. OUTCOME MEASURES: Information collected
      included time to negative fluid balance (in hours), CICU and hospital length of
      stay (in days), and the number of patients who had delayed sternal closure and/or
      underwent cardiopulmonary bypass. RESULTS: Data were available for 65 subjects.
      Median fluid administration in the 24 hours postoperatively was 43.9 cc/kg/day
      (interquartile range: 32.9-61.0). Mean time to negative fluid balance was 25.0 +/
      12.8 hours. Time to negative fluid balance was not associated with time to
      extubation, CICU and hospital length of stay, or change in weight-for-age z-score
      at intensive care unit discharge. CONCLUSION: Time to negative fluid balance is
      not associated with duration of mechanical ventilation, CICU, and hospital length
      of stay in patients after undergoing systemic-to-pulmonary artery shunt
      palliation. The utility of a restricted fluid strategy immediately following
      infant heart surgery is questionable.

PMID- 24444099
TI  - Aged care safety dilemma: caring-for-self versus caring-for-residents.
AB  - AIM: To identify aged care specific work health and safety management issues by
      applying James Reason's safety culture theory to one residential aged care
      provider in Australia. METHODS: Qualitative, semi-structured interviews with
      frontline care staff at three residential care facilities - all operated by the
      same provider - garnered employee perceptions of the safety culture and aged care
      specific challenges in their work environment. Thematic analysis of participant
      responses against the premises of James Reason's safety culture theory was
      undertaken. RESULTS: An aged care safety dilemma exists for frontline staff
      between looking after their own safety, a fundamental premise in work health and
      safety management, and caring for residents. CONCLUSIONS: A 'culture of care' and
      professional identity inhibit safe behaviour. Organisational learning from
      incidents could assist employees in putting their safety first in care scenarios.
      Evaluating perceived barriers to carer-first safety practices, such as
      understaffing or time pressures, may facilitate safer outcomes.

PMID- 24444100
TI  - Cutaneous mast cell tumor (Mastocytoma): cyto- histopathological and
      haematological investigations.
AB  - Cutaneous mast cell tumours (MCTs) are the most common skin tumours in dogs. Due
      to the prevalence of canine MCTs and the variable biologic behavior of this
      disease, accurate prognostication and a thorough understanding of MCT biology are
      critical for the treatment of this disease. A cytologic diagnosis of mast cell
      tumor with evidence of prior hemorrhage was made, and the masses were surgically
      removed. Cytological evaluation of fine-needle aspirates from the cutaneous mass
      from the axillary comprised many well-differentiated, highly granulated mast
      cells with moderate numbers of eosinophils. Nuclei were varied in size and shape
      with high nuclear'to'cytoplasmic ratio, prominent nucleoli, marked atypical and
      mitotic figures. Microscopically, mass consisted of sheets of neoplastic round
      cells that formed nonencapsulated nodules in the dermis and infiltrated into the
      adjacent dermal collagen, and also there was diffuse subcutis invasion of round
      to pleomorphic tumor cells. Tumor cells had moderate to abundant cytoplasm, round
      to ovoid nuclei with scattered chromatin, and mitotic figures. In this tumor,
      cytoplasmic granules showed atypical metachromasia. In addition, eosinophils were
      scattered among the mast cells at the periphery of the nodules. The presence of
      eosinophils and the observation, at high magnification, of cells with cytoplasmic
      metachromatic granules. Invasion of the deep subcutaneous fat or cutaneous
      muscles were a common feature of grade III tumour. Finally, a diagnosis of grade
      III cutaneous mast cell tumor was made. VIRTUAL SLIDES: The virtual slide(s) of
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4755249151157024.

PMID- 24444101
TI  - A validation study of memory and executive functions indexes in French-speaking
      healthy young and older adults.
AB  - Medial temporal lobe (MTL)/memory and frontal lobe (FL)/executive functions
      indexes are used to measure changes related to cognitive aging. These indexes are
      based on composite scores of neuropsychological tests validated in English
      speaking populations, and their use in aging research is growing in popularity.
      This study aimed at validating the MTL/memory and FL/executive functions indexes
      in French-speaking adults. Ninety-eight healthy participants (32 young and 66
      older adults) were tested on eight neuropsychological tests, three associated
      with MTL/memory functions and five associated with FL/executive functions. Factor
      analysis indicated that residual scores independent of age and associated with
      MTL/memory functions grouped under one factor, and residual scores associated
      with FL/executive functions grouped under another factor. Bootstrapping analysis
      with 1,000 resamples confirmed stability for seven neuropsychological tests. This
      study provides the first validation of the MTL/memory and FL/executive functions
      composite scores in French-speaking adults, which may be used to assess cognitive
      changes in aging research.

PMID- 24444102
TI  - [Development and validation of a Quebec classification of private residences with
      services welcoming of older persons].
AB  - Private Residential Care Facilities (RCFs) fill the gap between independent
      community living and institutional settings for seniors. There are marked
      differences between RCFs which make them difficult to compare. To address this
      issue, the objective of this study was to develop and validate a classification
      of RCFs based on their physical and organizational environments. RCF owners
      across Quebec were invited to complete a questionnaire that described the
      setting's physical and organizational environment. Different combinations of
      cluster analysis methods and statistical parameters were used to identify
      plausible classifications. The final choice was made by an expert committee.
      Overall, 552 owners returned the questionnaire. Three plausible classifications
      were submitted to the committee. The selected classification included five
      clusters that differed with regard to admission criteria, services offered and
      recreational activities. This classification could help health professionals
      select the RCF that best responds to older adults' needs.

PMID- 24444103
TI  - Genomic analysis of the differential response to experimental infection with
      porcine circovirus 2b.
AB  - Porcine circovirus type 2 (PCV2) is the etiological agent of a group of
      associated diseases (PCVAD) that affect production efficiency and can lead to
      mortality. Using different crossbred lines of pigs, we analyzed host genetic
      variation of viral load, immune response and weight change following experimental
      infection with a PCV2b strain (n = 386). Pigs expressed variation in the
      magnitude and initiation of viremia and immune response recorded weekly until 28
      days post-infection. A higher viral load was correlated with weight gain (r = 
      0.26, P < 0.0001) and presence of PCV2-specific antibodies (IgM, r = 0.26-0.34, P
      < 0.0001; IgG, r = 0.17-0.20, P < 0.01). In genome-wide association analyses of
      the responses at different time points, the proportions of phenotypic variation
      explained by combined effects of 56 433 SNPs were 34.8-59.4% for viremia, 10.1
      59.5% for antibody response and 5.6-14.9% for weight change. Relationships
      between genomic prediction of overall viral load and weight gain during the first
      weeks of challenge were negative (-0.21 and -0.24 respectively, P < 0.0001).
      Individuals that carried more favorable alleles across three SNPs on SSC9 (0.60
      Mb) and SSC12 (6.8 and 18.2 Mb) partially explained this relationship, having
      lower viral load (P < 0.0001); lower viremia at day 14 (P < 0.0001), day 21 (P <
      0.01) and day 28 (P < 0.05) and greater overall average daily gain during
      infection (ADGi ; P < 0.01), ADGi at week 3 (P < 0.001) and week 4 (P < 0.01).
      These additive genetic relationships could lead to molecular solutions to improve
      animal health and reduce production costs.

PMID- 24444104
TI  - High Mg effective incorporation in Al-rich AlxGa1 - xN by periodic repetition of
      ultimate V/III ratio conditions.
AB  - According to first-principles calculations, the solubility of Mg as a substitute
      for Ga or Al in AlxGa1 - xN bulk is limited by large, positive formation
      enthalpies. In contrast to the bulk case, the formation enthalpies become
      negative on AlxGa1 - xN surface. In addition, the N-rich growth atmosphere can
      also be favorable to Mg incorporation on the surface by changing the chemical
      potentials. On the basis of these special features, we proposed a modified
      surface engineering technique that applies periodical interruptions under an
      ultimate V/III ratio condition (extremely N-rich), to enhance Mg effective
      incorporation. By optimizing the interruption conditions (2 nm interruption
      interval with 2 s interruption time), the enhancement ratio can be up to about 5
      in the Al0.99Ga0.01N epilayer. 

PMID- 24444105
TI  - A diagnostic immunohistochemical panel for yolk sac (primitive endodermal)
      tumours based on an immunohistochemical comparison with the human yolk sac.
AB  - AIMS: To establish a diagnostic immunohistochemical panel for various histotypes
      of yolk sac (primitive endodermal) tumours (YSTs) by comparison with the human
      yolk sac (HYS) immunophenotype. METHODS AND RESULTS: Twenty-five YSTs showing
      either classical patterns (CPs) of histology (microcystic/reticular, n = 14;
      polyvesicular, n = 1; and hepatoid, n = 1) or somatic glandular patterns (SGPs; n
      = 9) were analysed for expression of alpha-fetoprotein (AFP), glypican-3 (GPC3),
      villin, hepatocyte paraffin-1 (HepPar-1), CDX2, SALL4 and LIN28. AFP expression
      was constantly heterogeneous in CPs but tended to be focal/absent in SGPs. GPC3
      was diffuse in CPs but heterogeneous (seven cases) or focal/absent (two cases) in
      SGPs. HepPar-1 expression was focal in all but three cases (diffuse in one CP
      hepatoid and two SGPs). CDX2 positivity was focal in CPs but heterogeneous (seven
      cases) or diffuse (two cases) in SGPs. Villin, SALL4 and LIN28 were diffusely
      positive in nearly all cases. CONCLUSIONS: CPs reproduce the immunophenotype of
      HYS and early endoderm with variable expression of both AFP and markers of early
      gut or hepatic differentiation. SGPs with intestinal differentiation often have
      incomplete immunophenotypes. A differential diagnosis panel, including both
      markers of pluripotentiality (SALL4 and/or LIN28) and endoderm (AFP, GPC3 and
      villin), is proposed. It identifies overlapping multidifferentiation of primitive
      and somatic immunophenotypes, supporting the recently proposed term of primitive
      endodermal tumours.

PMID- 24444106
TI  - Endoscopic removal of eroded gastric band using strangulation technique with a
      mechanical lithotriptor as a minimally invasive procedure.

PMID- 24444107
TI  - Intraligand charge-transfer excited states in Re(I) complexes with donor
      substituted dipyridophenazine ligands.
AB  - The donor-acceptor ligands 11-(4-diphenylaminophenyl)dipyrido[3,2-a:2',3'
      c]phenazine (dppz-PhNPh2) and 11-(4-dimethylaminophenyl)dipyrido[3,2-a:2',3'
      c]phenazine (dppz-PhNMe2), and their rhenium complexes, [Re(CO)3X] (X = Cl(-),
      py, 4-dimethylaminopyridine (dmap)), are reported. Crystal structures of the two
      ligands were obtained. The optical properties of the ligands and complexes are
      dominated by intraligand charge transfer (ILCT) transitions from the amine to the
      dppz moieties with lambdaabs = 463 nm (epsilon = 13 100 M(-1) cm(-1)) for dppz
      PhNMe2 and with lambdaabs = 457 nm (epsilon = 16 900 M(-1) cm(-1)) for dppz
      PhNPh2. This assignment is supported by CAM-B3LYP TD-DFT calculations. These
      ligands are strongly emissive in organic solvents and, consistent with the ILCT
      character, show strong solvatochromic behavior. Lippert-Mataga plots of the data
      are linear and yield DeltaMU values of 22 D for dppz-PhNPh2 and 20 D for dppz
      PhNMe2. The rhenium(I) complexes are less emissive, and it is possible to measure
      resonance Raman spectra. These data show relative band intensities that are
      virtually unchanged from lambdaexc = 351 to 532 nm, consistent with a single
      dominant transition in the visible region. Resonance Raman excitation profiles
      are solvent sensitive; these data are modeled using wavepacket theory yielding
      reorganization energies ranging from 1800 cm(-1) in toluene to 6900 cm(-1) in
      CH3CN. The excited state electronic absorption and infrared spectroscopy reveal
      the presence of dark excited states with nanosecond to microsecond lifetimes that
      are sensitive to the ancillary ligand on the rhenium. These dark states were
      assigned as phenazine-based (3)ILCT states by time-resolved infrared
      spectroscopy. Time-resolved infrared spectroscopy shows transient features in
      which Deltanu(CO) is approximately -7 cm(-1), consistent with a ligand-centered
      excited state. Evidence for two such states is seen in mid-infrared transient
      spectra. 

PMID- 24444108
TI  - Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense
      mutation in a pediatric patient with rapidly progressive retinal dystrophy.
AB  - BACKGROUND: A pediatric patient presented with rapidly progressive vision loss,
      nyctalopia and retinal dystrophy. This is the first report of homozygosity for
      the p.Arg602Trp mutation in the ABCA4 gene. The child became legally blind within
      a period of 2 years. CASE PRESENTATION: An eight year-old Hispanic female
      presented with bilateral decreased vision following a febrile gastrointestinal
      illness with nausea and vomiting. Extensive workup involved pediatric infectious
      disease and rheumatology consultations.Initial visual acuity was 20/60 at
      distance and 20/30 at near in both eyes. Rapidly progressive vision loss occurred
      during a 2-year period resulting in visual acuities of 20/200 at distance in both
      eyes. Fundus exam disclosed attenuated vessels and multiple subretinal blister
      like elevations. Optical coherence tomography showed far more lesions than were
      clinically evident with different levels of elevation. Autofluorescence imagery
      showed dramatic and widespread geographic areas of atrophy. The deposits that
      appeared drusen-like on clinical exam were hyperfluorescent, consistent with
      lipofuscin deposits containing A2e (N-retinylidene-N-retinylethanolamine)
      indicative of RPE cell dysfunction. Electroretinography was consistent with cone
      dystrophy, with relative preservation of rod function. Blood analysis and
      rheumatology evaluation found no evidence of a diffuse post
      infectious/inflammatory process. The unique and rapid progression of her
      subretinal blister-like lesions was documented by fluorescein angiography,
      optical coherence tomography, autofluorescence imagery, and fundus photography.
      Family pedigree history disclosed consanguinity, her parents being first cousins.
      DNA analysis by whole exomic sequencing revealed homozygosity of p.Arg602Trp in
      the ABCA4 gene. CONCLUSION: The pediatric patient presented with a striking
      clinical appearance and dramatic rate of progression that was clinically more
      characteristic of an infectious or inflammatory process. This case expands the
      diverse range of phenotypes attributed to ABCA4 mutations and further supports
      the role of whole exome sequencing as a powerful new tool available to aid
      clinicians in establishing diagnosis for challenging cases.

PMID- 24444110
TI  - Altitude is positively correlated to race time during the marathon.
AB  - Completing a marathon (42.2 km) is one of the more challenging sports activities.
      Besides the distance, the ambient conditions of the race (altitude, temperature,
      etc) can increase the physiological demands of the event. The purpose of this
      study was to investigate the relation between the altitude of the city in which
      the marathon is held and the marathon race time. For this purpose, we sought the
      race times of 16 popular marathons performed at different altitudes above sea
      level (range from ~0 to 2800 meters above sea level). In these competitions, we
      analyzed the race times of the female and male runners who finished from 21(st)
      to 100(th) position. We excluded the top 20 male and female finishers from the
      analysis because elite athletes usually compete in marathons held at low
      altitudes above sea level. Ambient temperature, the positive cumulative elevation
      gain, and the number of participants were used as control variables. Finishing
      time in the marathon was positively correlated with the altitude of the
      competition for both male (r=0.78; p<0.05) and female participants (r=0.73;
      p<0.05). On average, each increase of 1000 meters above sea level augmented
      marathon race time by 10.8+/-0.6% in men and 12.3+/-0.7% in women. Compared to
      race times in the Rotterdam marathon (held at 0 meters above sea level), the time
      taken to complete the marathon was significantly higher in competitions held at
      an altitude of over 700 meters. In conclusion, the time taken to complete a
      marathon strongly depends on the altitude of the city in which the marathon is
      held. Selecting marathon competitions close to 0 m above sea level is a good
      strategy to maximize marathon performance.

PMID- 24444109
TI  - High-throughput strategies for penicillin G acylase production in rE. coli fed
      batch cultivations.
AB  - BACKGROUND: Penicillin G acylase (PGA) is used industrially to catalyze the
      hydrolysis of penicillin G to obtain 6-aminopenicillanic acid. In Escherichia
      coli, the most-studied microorganism for PGA production, this enzyme accumulates
      in the periplasmic cell space, and temperature plays an important role in the
      correct synthesis of its subunits. RESULTS: This work investigates the influence
      of medium composition, cultivation strategy, and temperature on PGA production by
      recombinant E. coli cells. Shake flask cultures carried out using induction
      temperatures ranging from 18 to 28 degrees C revealed that the specific enzyme
      activity achieved at 20 degrees C (3000 IU gDCW-1) was 6-fold higher than the
      value obtained at 28 degrees C. Auto-induction and high cell density fed-batch
      bioreactor cultures were performed using the selected induction temperature, with
      both defined and complex media, and IPTG and lactose as inducers. Final biomass
      concentrations of 100 and 120 gDCW L-1, and maximum enzyme productivities of 7800
      and 5556 IU L-1 h-1, were achieved for high cell density cultures using complex
      and defined media, respectively. CONCLUSIONS: To the best of our knowledge, the
      volumetric enzyme activity and productivity values achieved using the complex
      medium are the highest ever reported for PGA production using E. coli. Overall
      PGA recovery yields of 64 and 72% after purification were achieved for crude
      extracts obtained from cells cultivated in defined and complex media,
      respectively. The complex medium was the most cost-effective for PGA production,
      and could be used in both high cell density and straightforward auto-induction
      protocols.

PMID- 24444111
TI  - Detailed process of shell construction in the photosynthetic testate amoeba
      Paulinella chromatophora (euglyphid, Rhizaria).
AB  - Most euglyphids, a group of testate amoebae, have a shell that is constructed
      from numerous siliceous scales. The euglyphid Paulinella chromatophora has
      photosynthetic organelles (termed cyanelles or chromatophores), allowing it to be
      cultivated more easily than other euglyphids. Like other euglyphids, P.
      chromatophora has a siliceous shell made of brick-like scales. These scales are
      varied in size and shape. How a P. chromatophora cell makes this shell is still a
      mystery. We examined shell construction process in P. chromatophora in detail
      using time-lapse video microscopy. The new shell was constructed by a specialized
      pseudopodium that laid out each scale into correct position, one scale at a time.
      The present study inferred that the sequence of scale production and secretion
      was well controlled.

PMID- 24444112
TI  - Emerging methods for identifying monoclonal antibodies with low propensity to
      self-associate during the early discovery process.
AB  - Subcutaneous delivery of concentrated monoclonal antibodies (mAbs) is complicated
      by the propensity of mAbs to self-associate at elevated concentrations, which can
      lead to undesirable solution properties such as aggregation and abnormally high
      viscosity. Therefore, the selection of mAb candidates with low propensity to self
      associate during early antibody discovery can significantly reduce challenges
      that may occur later during antibody development. However, it is difficult to use
      conventional biophysical methods for measuring weak mAb self-interactions during
      antibody discovery given the large number of antibody candidates as well as their
      low concentrations and purities. Nevertheless, significant progress has been made
      recently in adapting conventional biophysical methods as well as developing new
      ones for early identification of mAbs with low self-association propensities,
      which we highlight in this editorial. These advances should improve the selection
      of mAb candidates suitable for the extreme requirements of concentrated
      formulations necessary for subcutaneous delivery of therapeutic antibodies. 

PMID- 24444114
TI  - Telemedicine, FAST-MAG and participation in clinical trials.

PMID- 24444113
TI  - Patient-specific computer-based decision support in primary healthcare--a
      randomized trial.
AB  - BACKGROUND: Computer-based decision support systems are a promising method for
      incorporating research evidence into clinical practice. However, evidence is
      still scant on how such information technology solutions work in primary
      healthcare when support is provided across many health problems. In Finland, we
      designed a trial where a set of evidence-based, patient-specific reminders was
      introduced into the local Electronic Patient Record (EPR) system. The aim was to
      measure the effects of such reminders on patient care. The hypothesis was that
      the total number of triggered reminders would decrease in the intervention group
      compared with the control group, indicating an improvement in patient care.
      METHODS: From July 2009 to October 2010 all the patients of one health center
      were randomized to an intervention or a control group. The intervention consisted
      of patient-specific reminders concerning 59 different health conditions triggered
      when the healthcare professional (HCP) opened and used the EPR. In the
      intervention group, the triggered reminders were shown to the HCP; in the control
      group, the triggered reminders were not shown. The primary outcome measure was
      the change in the number of reminders triggered over 12 months. We developed a
      unique data gathering method, the Repeated Study Virtual Health Check (RSVHC),
      and used Generalized Estimation Equations (GEE) for analysing the incidence rate
      ratio, which is a measure of the relative difference in percentage change in the
      numbers of reminders triggered in the intervention group and the control group.
      RESULTS: In total, 13,588 participants were randomized and included. Contrary to
      our expectation, the total number of reminders triggered increased in both the
      intervention and the control groups. The primary outcome measure did not show a
      significant difference between the groups. However, with the inclusion of
      patients followed up over only six months, the total number of reminders
      increased significantly less in the intervention group than in the control group
      when the confounding factors (age, gender, number of diagnoses and medications)
      were controlled for. CONCLUSIONS: Computerized, tailored reminders in primary
      care did not decrease during the 12 months of follow-up time after the
      introduction of a patient-specific decision support system. TRIAL REGISTRATION:
      ClinicalTrial.gov NCT00915304.

PMID- 24444115
TI  - Stroke: More than a 'brain attack'.
AB  - Stroke is a life-altering event that potentially affects stroke survivors, their
      families, healthcare resources, and society in general. Stroke has often been
      described as 'brain attack', denoting emergency emphasis on the vascular
      pathology. Consequently, many national and provincial stroke strategies have
      emphasized vascular care through primary prevention strategies and thrombolysis.
      Despite being important initiatives, this has resulted in a stroke system that
      emphasizes the frontloading of stroke care, focusing on the vascular pathology.
      The advent of thrombolysis therapy has benefited a small proportion of patients
      while a vast majority are still affected by stroke-related impairments.
      Management of the vascular elements of stroke is important; however, the impact
      of rehabilitation on stroke recovery has been relatively undervalued. Stroke care
      is in need of a revolution toward a more comprehensive and balanced approach. It
      is anticipated that the major focus of stroke care will include promoting
      recovery, in line with the growing evidence on stroke rehabilitation
      interventions. A paradigm shift is necessary to ensure that comprehensive and
      balanced stroke care which incorporates rehabilitation is taken into account,
      leading to a stroke care system where patient needs are managed both as a 'brain
      attack' and an 'injured brain'. 

PMID- 24444116
TI  - Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG)
      phase 3 trial: Part 1 - rationale and general methods.
AB  - RATIONALE: Prehospital initiation by paramedics may enable delivery of
      neuroprotective therapies to stroke patients in the hyperacute period when they
      are most effective in preclinical studies. Magnesium is neuroprotective in
      experimental stroke models and has been shown to be safe with signals of
      potential efficacy when started early after onset of human cerebral ischemia.
      AIMS: (a) To demonstrate that paramedic initiation of the neuroprotective agent
      magnesium sulfate in the field is an efficacious and safe treatment for acute
      stroke; (b) To demonstrate that field enrollment of acute stroke patients is a
      practical and feasible strategy for phase 3 stroke trials, permitting enrollment
      of greater numbers of patients in hyperacute time windows. DESIGN: Multicenter,
      randomized, double-blinded, placebo-controlled, pivotal clinical trial. STUDY
      PROCEDURES: The study is enrolling 1700 patients (850 in each arm) with likely
      acute stroke, including both cerebral infarction and intracerebral hemorrhage
      patients. Inclusion criteria are: (a) likely stroke as identified by the modified
      Los Angeles Prehospital Stroke Screen (mLAPSS), (b) age 40-95, (c) symptom onset
      within 2 h of treatment initiation, and (d) deficit present >=15 min. Paramedics
      administer a loading dose of magnesium sulfate (Mg) or matched placebo in the
      field, 4 grams over 15 min. In the Emergency Department, a maintenance infusion
      follows, 16 grams Mg or matched placebo over 24 h. OUTCOMES: The primary endpoint
      is the modified Rankin Scale measure of global disability, assessed using the
      Rankin Focused Assessment, 90 days after treatment. Secondary efficacy endpoints
      include the NIHSS (neurologic deficit), Barthel Index (activities of daily
      living), and the Stroke Impact Scale (quality of life).

PMID- 24444117
TI  - Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG)
      phase 3 trial: Part 2 - prehospital study methods.
AB  - RATIONALE: In acute stroke, the volume of salvageable brain tissue is maximal at
      onset and declines rapidly with time. Prehospital start of clinical trial
      interventions would enable delivery of neuroprotective agents, such as magnesium
      sulfate, to stroke patients in the hyperacute period when they are potentially
      most effective. AIMS: A broad aim of the FAST-MAG study is to develop and
      validate techniques to perform pivotal trials of neuroprotective therapies for
      acute stroke in the prehospital setting. In tandem with an accompanying general
      trial design article, this manuscript provides a detailed overview of several
      novel prehospital study methods employed in the NIH FAST-MAG Trial. DESIGN:
      Multicenter, randomized, double-blinded, placebo-controlled, pivotal clinical
      trial. Special Prehospital Procedures Distinctive prehospital methods deployed in
      FAST-MAG include: identifying likely stroke patients using the Los Angeles
      Prehospital Stroke Screen; eliciting explicit informed consent from patients or
      on scene legally authorized representatives via cellphone discussion with off
      scene physicians; paramedic rating of pretreatment stroke severity using the Los
      Angeles Motor Scale; assigning patients to a study arm using blinded, pre
      encounter randomization; facilitating continuity of study infusion from the field
      to the ED by stocking ambulances with study kits including both field and
      hospital doses; and electronic fax consent signature documentation by
      geographically separated subjects and enrolling physicians. DISCUSSION: The suite
      of prehospital trial methods developed for the FAST-MAG Trial enable enrollment
      of patients in very early time windows, including the hyperacute, 'golden hour'
      period immediately after stroke onset.

PMID- 24444118
TI  - Aortic arch atheroma and further cardiovascular events in stroke patients.

PMID- 24444119
TI  - Arterial stiffness in patients with ischemic attack.

PMID- 24444120
TI  - Endovascular therapy did not improve expected prognosis after i.v. fibrinolysis:
      a retrospective analysis based on a nationwide Danish registry.

PMID- 24444121
TI  - Measurement of the levels of leptin, BDNF associated with polymorphisms LEP
      G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is a cluster of metabolic risk factors including
      dyslipidemia, impaired glucose tolerance, hypertension and central obesity. BDNF
      (Brain-derived neurotrophic factor) and leptin have been implied in the energy
      homeostasis. The purposes of this study were to examine concentrations of leptin,
      BDNF and biochemical parameters in metabolic-syndrome subjects and healthy
      controls, and also to search for associations of leptin gene (LEP) G2548A, leptin
      receptor gene (LEPR) Gln223Arg, and BDNF gene (BDNF) Val66Met polymorphisms with
      leptin levels, BDNF levels and metabolic syndrome among Thais. METHODS: The case
      controlled design was performed using 322 Thai volunteers (160 metabolic-syndrome
      subjects; 162 controls) during the health screening program. Metabolic syndrome
      was assessed by using the modified National Cholesterol Education Program, Adult
      Treatment Panel III criteria. The levels of leptin, BDNF, insulin, glucose and
      lipids were measured in samples. Genotyping of LEP G2548A, LEPR Gln223Arg and
      BDNF Val66Met was carried out using polymerase chain reaction-restriction
      fragment length polymorphism technique. RESULTS: Serum leptin levels were
      significantly higher in the metabolic-syndrome group than the control group (p <
      0.01), but the BDNF difference between them was not significant. Significant
      associations of LEPR Gln223Arg polymorphism were found with leptin and glucose
      levels (p < 0.05), after adjusting for potential covariates. This LEPR
      polymorphism in the metabolic-syndrome group was also significantly more frequent
      than in the control group (p < 0.05). However, other gene polymorphisms, LEP
      G2548A and BDNF Val66Met, showed no significant relationship with leptin levels,
      BDNF levels or metabolic syndrome. CONCLUSION: These findings suggest leptin
      levels are linked with metabolic syndrome. LEPR Gln223Arg polymorphism impacted
      leptin concentrations, and this gene polymorphism may influence susceptibility to
      metabolic syndrome among Thais.

PMID- 24444122
TI  - Palladium-catalyzed oxidative olefination of phenols bearing removable directing
      groups under molecular oxygen.
AB  - An efficient Pd(II)-catalyzed oxidative olefination of phenols bearing removable
      directing groups with molecular oxygen as the sole oxidant has been developed.
      This reaction protocol provides an efficient and robust synthetic tool for the
      synthesis of o-alkenyl phenols under mild conditions. 

PMID- 24444123
TI  - Interactions with soil biota shift from negative to positive when a tree species
      is moved outside its native range.
AB  - Studies evaluating plant-soil biota interactions in both native and introduced
      plant ranges are rare, and thus far have lacked robust experimental designs to
      account for several potential confounding factors. Here, we investigated the
      effects of soil biota on growth of Pinus contorta, which has been introduced from
      Canada to Sweden. Using Swedish and Canadian soils, we conducted two glasshouse
      experiments. The first experiment utilized unsterilized soil from each country,
      with a full-factorial cross of soil origin, tree provenance, and fertilizer
      addition. The second experiment utilized gamma-irradiated sterile soil from each
      country, with a full-factorial cross of soil origin, soil biota inoculation
      treatments, tree provenance, and fertilizer addition. The first experiment showed
      higher seedling growth on Swedish soil relative to Canadian soil. The second
      experiment showed this effect was due to differences in soil biotic communities
      between the two countries, and occurred independently of all other experimental
      factors. Our results provide strong evidence that plant interactions with soil
      biota can shift from negative to positive following introduction to a new region,
      and are relevant for understanding the success of some exotic forest plantations,
      and invasive and range-expanding native species. 

PMID- 24444124
TI  - The partial thromboplastin time: reply.

PMID- 24444125
TI  - Staphylococcal enterotoxin sensitization in a community-based population: a
      potential role in adult-onset asthma.
AB  - BACKGROUND: Recent studies suggest that Staphylococcus aureus enterotoxin
      sensitization is a risk factor for asthma. However, there is a paucity of
      epidemiologic evidence on adult-onset asthma in community-based populations.
      OBJECTIVE: We sought to evaluate the epidemiology and the clinical significance
      of staphylococcal enterotoxin sensitization in community-based adult populations.
      METHODS: The present analyses were performed using the baseline data set of
      Korean adult population surveys, consisting of 1080 adults (mean age = 60.2
      years) recruited from an urban and a rural community. Questionnaires,
      methacholine challenge tests, and allergen skin tests were performed for defining
      clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific
      IgE using ImmunoCAP. RESULTS: Staphylococcal enterotoxin sensitization (>= 0.35
      kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex,
      current smoking, advanced age (>= 61 years), and inhalant allergen sensitization.
      Current asthma was mostly adult onset (>= 18 years old) and showed independent
      associations with high enterotoxin-specific IgE levels in multivariate logistic
      regression tests. In multivariate linear regressions, staphylococcal enterotoxin
      specific IgE level was identified as the major determinant factor for total IgE
      level. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcal enterotoxin
      sensitization was independently associated with adult-onset asthma in adult
      community populations. Strong correlations between the enterotoxin-specific IgE
      and total IgE levels support the clinical significance. The present findings
      warrant further studies for the precise roles of staphylococcal enterotoxin
      sensitization in the asthma pathogenesis.

PMID- 24444126
TI  - Nutritional screening tools and anthropometric measures associate with hospital
      discharge outcomes in older people.
AB  - AIM: To examine the association of nutritional screening tools (NSTs) and
      anthropometric measures with hospital outcomes in older people. METHODS: In 172
      patients aged >=70 years admitted to a Geriatric Evaluation Management Unit
      (GEMU), nutritional status was measured using the Mini-Nutritional Assessment
      (MNA), MNA-short form (MNA-SF), Geriatric Nutritional Risk Index (GNRI),
      Simplified Nutritional Appetite Questionnaire, calf circumference (CC), mid-arm
      circumference (MAC) and BMI. RESULTS: Malnutrition according to the MNA occurred
      in 53 (31%) patients. Functional change was associated with GNRI (Beta
      coefficient (beta), 95% CI = 0.17, 0.001-0.33) and CC (beta, 95% CI = 0.17, 0.01
      0.33); GEMU length of stay was associated with MNA-SF-BMI (beta, 95% CI = -0.02, 
      0.003 to -0.004) and MNA-SF-CC (beta, 95% CI = -0.02, -0.003 to -0.001). MAC was
      associated with discharge to higher level of care (OR, 95% CI = 0.88, 0.81-0.96).
      CONCLUSION: In hospitalised older people, admission NSTs and anthropometric
      measures associate with discharge outcomes.

PMID- 24444127
TI  - A micropatterned hepatocyte coculture model for assessment of liver toxicity
      using high-content imaging analysis.
AB  - The current landscape of in vitro models used to identify drug- or chemical
      induced hepatotoxicity relies heavily on cell culture models consisting of HepG2,
      induced pluripotent stem cell-derived, or primary hepatocytes. While these in
      vitro models offer powerful approaches for predicting toxicity, each system has
      challenges, including variable metabolic capacity, brief ex vivo life span in
      culture, and adoption with standard automated microscopy high-content screening
      (HCS) systems to measure reproducibility data at the single-cell level. In this
      report we introduce a novel primary hepatocyte coculture model, HepatoPacTM, as
      an alternative to current model systems for evaluation of in vitro hepatotoxicity
      in 96-well microtiter plate format examined by HCS. The coculture model consists
      of primary hepatocytes that are micropatterned to form a discrete
      microarchitecture or "hepatocyte islands" that are surrounded by supporting
      fibroblasts resulting in long-term viability and metabolic function of primary
      hepatocytes. Using multiple HCS image capture and image analysis strategies, we
      established methods to interrogate various morphometric parameters, such as size,
      shape, and intensity, at the island or single-cell level. We applied these
      approaches to identify subpopulations of both fibroblasts and hepatocytes that
      exhibited alterations in nuclear parameters, cell permeability, mitochondria
      function, and apoptosis using known reference control compounds and an eight
      point dose curve. Subpopulation analysis with additional bioprobe sets can
      provide a powerful means of addressing differential cell and tissue
      susceptibilities during compound profiling. Our data show that the HepatoPac is
      amendable for HCS imaging applications and provides a unique approach for
      studying hepatotoxicity over prolonged periods of time.

PMID- 24444128
TI  - Database for exchangeable gene trap clones: pathway and gene ontology analysis of
      exchangeable gene trap clone mouse lines.
AB  - Gene trapping in embryonic stem (ES) cells is a proven method for large-scale
      random insertional mutagenesis in the mouse genome. We have established an
      exchangeable gene trap system, in which a reporter gene can be exchanged for any
      other DNA of interest through Cre/mutant lox-mediated recombination. We isolated
      trap clones, analyzed trapped genes, and constructed the database for
      Exchangeable Gene Trap Clones (EGTC) [http://egtc.jp]. The number of registered
      ES cell lines was 1162 on 31 August 2013. We also established 454 mouse lines
      from trap ES clones and deposited them in the mouse embryo bank at the Center for
      Animal Resources and Development, Kumamoto University, Japan. The EGTC database
      is the most extensive academic resource for gene-trap mouse lines. Because we
      used a promoter-trap strategy, all trapped genes were expressed in ES cells. To
      understand the general characteristics of the trapped genes in the EGTC library,
      we used Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway analysis and
      found that the EGTC ES clones covered a broad range of pathways. We also used
      Gene Ontology (GO) classification data provided by Mouse Genome Informatics (MGI)
      to compare the functional distribution of genes in each GO term between trapped
      genes in the EGTC mouse lines and total genes annotated in MGI. We found the
      functional distributions for the trapped genes in the EGTC mouse lines and for
      the RefSeq genes for the whole mouse genome were similar, indicating that the
      EGTC mouse lines had trapped a wide range of mouse genes. 

PMID- 24444129
TI  - Playbill.

PMID- 24444130
TI  - Aftermath of Typhoon Haiyan: the imminent epidemic of waterborne illnesses in
      Leyte, Philippines.

PMID- 24444131
TI  - Impact of dual-polarization radar technology and Twitter on the Hattiesburg,
      Mississippi tornado.
AB  - OBJECTIVE: Dual-Polarization Radar and Twitter were analyzed to determine the
      impact on injuries sustained by the Hattiesburg EF-4 tornado. METHOD: Tracking
      data provided from the Dual-Pol radar systems in National Weather Service Jackson
      were reviewed. Twitter data from four local Twitter handles were obtained. The
      change in tweets and followers for the day of the storm were compared to
      historical averages. A Student t-test was utilized in determining statistical
      significance (p<0.05). Medical records from two local emergency departments were
      reviewed for patients treated up to 24 hours after the tornado. An Injury
      Severity Score (ISS) was calculated for trauma records related to the tornado.
      RESULTS: Radar detection of the tornado gave approximately 30 minutes of advanced
      warning time. Statistical significance in follower growth was seen in all four
      Twitter handles. Out of 50 patients, the average ISS was 3.9 with a range of 1 to
      29. There were zero fatalities. CONCLUSIONS: An ISS average of 3.9 was
      significantly less than two previous tornadoes of similar strength that occurred
      prior to increased usage of Dual-pol radar and Twitter as a means for
      communicating severe weather information. Early detection from Dual-pol radar
      improved warning time. Tweets informed citizens to seek appropriate shelter.
      (Disaster Med Public Health Preparedness. 2013;7:585-592).

PMID- 24444132
TI  - Second Evidence Aid Conference: prioritizing evidence in disaster aid.
AB  - The Second Evidence Aid Conference took place in Brussels, Belgium, in October
      2012, jointly organized by Evidence Aid and the Belgian Red Cross-Flanders. It
      provided an opportunity to build on the discussions from the 2011 First Evidence
      Aid Conference in Oxford, England, and prioritize the future work of Evidence
      Aid. Within the plenary presentations, discussions, and small work groups, the
      more than 80 international participants addressed issues regarding the need, use,
      and prioritization of evidence. Three parallel workshops focused on the
      prioritization of research, systematic reviews, and data to be collected during
      disasters, leading to a suggested prioritization framework and a commitment to
      identify key areas for evidence in disasters. Working with a wide variety of
      people and organizations from the disaster and humanitarian sectors, Evidence Aid
      will take this framework and develop a list of top priority questions in need of
      research and systematic reviews. Although Evidence Aid will not be able to
      address all of the research questions that will be identified in this process, it
      will collect them for sharing with relevant agencies. (Disaster Med Public Health
      Preparedness. 2013;7:593-596). 

PMID- 24444133
TI  - Assessing functional needs sheltering in Pike County, Kentucky: using a community
      assessment for public health emergency response.
AB  - OBJECTIVE: During 2009-2011, Pike County, Kentucky, experienced a series of
      severe weather events that resulted in property damage, insufficient potable
      water, and need for temporary shelters. A Community Assessment for Public Health
      Emergency Response (CASPER) survey was implemented for future planning. CASPER
      assesses household health status, preparedness level, and anticipated demand for
      shelters. METHODS: We used a 2-stage cluster sampling design to randomly select
      210 representative households for in-person interviews. We estimated the
      proportion of households with children aged 2 years or younger; adults aged 65
      years or older; and residents with chronic health conditions, visual impairments,
      physical limitations, and supplemental oxygen requirements. RESULTS: Of all
      households surveyed, 8% included children aged 2 years or younger, and 27%
      included adults aged 65 years or older. The most common chronic health conditions
      were heart disease (51%), diabetes (28%), lung disease (23%), and asthma (21%).
      Visual impairments were reported in 29% of households, physical limitations in
      24%, and supplemental oxygen use in 12%. CONCLUSIONS: Pike County residents
      should be encouraged to maintain an adequate supply of medications and copies of
      their prescriptions. Emergency response plans should include transportation for
      persons with physical limitations; and shelter plans should include sufficient
      medically trained staff and adequate supplies of infant formula, pharmaceuticals,
      and supplemental oxygen. (Disaster Med Public Health Preparedness. 2013;7:597
      602).

PMID- 24444134
TI  - Nodal, pulmonary and pleural gliomatosis in a 42-year-old-male with non
      seminomatous testicular germ cell cancer.

PMID- 24444135
TI  - Quantitative trait loci for magnitude of the plasma cortisol response to
      confinement in rainbow trout.
AB  - Better understanding of the mechanisms underlying interindividual variation in
      stress responses and their links with production traits is a key issue for
      sustainable animal breeding. In this study, we searched for quantitative trait
      loci (QTL) controlling the magnitude of the plasma cortisol stress response and
      compared them to body size traits in five F2 full-sib families issued from two
      rainbow trout lines divergently selected for high or low post-confinement plasma
      cortisol level. Approximately 1000 F2 individuals were individually tagged and
      exposed to two successive acute confinement challenges (1 month interval). Post
      stress plasma cortisol concentrations were determined for each fish. A medium
      density genome scan was carried out (268 markers, overall marker spacing less
      than 10 cM). QTL detection was performed using qtlmap software, based on an
      interval mapping method (http://www.inra.fr/qtlmap). Overall, QTL of medium
      individual effects on cortisol responsiveness (<10% of phenotypic variance) were
      detected on 18 chromosomes, strongly supporting the hypothesis that control of
      the trait is polygenic. Although a core array of QTL controlled cortisol
      concentrations at both challenges, several QTL seemed challenge specific,
      suggesting that responses to the first and to a subsequent exposure to the
      confinement stressor are distinct traits sharing only part of their genetic
      control. Chromosomal location of the steroidogenic acute regulatory protein
      (STAR) makes it a good potential candidate gene for one of the QTL. Finally,
      comparison of body size traits QTL (weight, length and body conformation) with
      cortisol-associated QTL did not support evidence for negative genetic
      relationships between the two types of traits. 

PMID- 24444136
TI  - Segregation analysis in families with Charcot-Marie-Tooth disease allows
      reclassification of putative disease causing mutations.
AB  - BACKGROUND: The identification of disease causing, or putative disease causing,
      mutations in index patients with Charcot-Marie-Tooth disease (CMT) allows for
      genetic testing of family members. Relevant variants identified in index patients
      are of either definite, likely or uncertain pathogenicity. The main objective of
      this study was to make an evaluation of the family investigations performed as
      part of the assessment of genetic variants of unknown clinical significance
      (VUS). METHODS: Between 2004 and 2010 molecular genetic family investigations
      were requested for 87 family members from 41 families harbouring PMP22dup or
      genetic variants in GJB1, MPZ, MFN2 and NEFL. Relatives were tested for the
      family mutation and data from the requisitions were evaluated by means of
      statistical tools. RESULTS: The results within each indication category are
      presented and discussed in detail. Twenty-two relatives (9 affected) from eight
      families were included in the segregation analyses, which invoked
      reclassification of three MFN2 mutations, two of which were de novo substitutions
      (c.2146_2148dup, c.692C > T). One MFN2 substitution was downgraded due to non
      segregation (c.1709 A > G), and a MPZ substitution (c.103 G > A) upgraded due to
      segregation with the phenotype in the family. CONCLUSIONS: The results allow for
      the evaluation of the patient phenotypes ascertained in families, as opposed to
      the phenotypic descriptions of index patients. They indicate that de novo MFN2
      mutations are regularly found in patients with a classical CMT2 phenotype. They
      also demonstrate the importance of a precise clinical and neurophysiologic
      diagnosis of affected family members. This particularly applies for the
      examination of variants of uncertain clinical significance. Finally, the fact
      that 14,6% of affected relatives tested for (probable or certain) pathogenic
      mutations were mutation negative, demonstrates that clinical evaluation alone is
      not always sufficient in order to determine their diagnosis. We believe that the
      results will aid in the estimation and planning of resources required for the
      various aspects of family evaluations in CMT.

PMID- 24444137
TI  - Factors determining intention to quit tobacco: exploring patient responses
      visiting public health facilities in India.
AB  - INTRODUCTION: Intention to quit and setting a quit date are key steps in the
      process towards improving quit rates and are thus an integral part of tobacco
      cessation efforts. The present study examined various motivating factors of
      "intention to quit" and "setting a quit date" in patients visiting public health
      facilities in two states of India. METHODS: A total of 1569 tobacco-users
      visiting public health facilities in 12 districts of the states of Andhra Pradesh
      and Gujarat were assessed through an interviewer-administered questionnaire.
      Bivariate and multivariable logistic regression was performed to assess the
      effect of socio-demographic characteristics, nicotine dependence, previous quit
      attempts and motivational factors on "intention to quit within 30 days" and
      "setting a quit date". RESULTS: Only 12% of patients intended to quit tobacco
      within 30 days and about 11% of them were ready to set a quit date. Respondents
      aged above 25 years were 53% less likely to quit tobacco within 30 days when
      compared to those below 25 years (95% Confidence Intervals [CI]: 0.22 to 0.99).
      Smokeless tobacco users were associated with an odds ratio (OR) of 2.05 (95% CI:
      1.15 to 3.65) for "setting a quit date" when compared to smokers. Those with 1 to
      5 previous quit attempts (in the past twelve months) were associated with an OR
      of 2.2 (95% CI: 1.38 to 3.51) for "intention to quit" and 2.46 (95% CI: 1.52 to
      3.96) for "setting a quit date". "Concern for personal health" and "setting an
      example for children" were associated with ORs of 3.42 (95% CI: 1.35 to 8.65) and
      2.5 (95% CI: 1.03 to 6.03) respectively for "setting a quit date". CONCLUSIONS:
      This study is amongst the first in India to explore factors associated with the
      "intention to quit" and "setting a quit date" among patients visiting public
      health facilities. Our findings suggest that socio-economic and individual-level
      factors are important factors depicting intention to quit and setting a quit
      date. We recommend the need for well-defined studies to understand the long term
      effects of factors influencing tobacco cessation for patients visiting public
      health facilities in India.

PMID- 24444138
TI  - Insulin-induced changes in microvascular vasomotion and capillary recruitment are
      associated in humans.
AB  - OBJECTIVE: Insulin-induced capillary recruitment is considered a significant
      regulator of overall insulin-stimulated glucose uptake. Insulin's action to
      recruit capillaries has been hypothesized to involve insulin-induced changes in
      vasomotion. Data directly linking vasomotion to capillary perfusion, however, are
      presently lacking. We, therefore, investigated whether insulin's actions on
      capillary recruitment and vasomotion were interrelated in a group of healthy
      individuals. We further assessed the role of capillary recruitment in the
      association between vasomotion and insulin-mediated glucose uptake. METHODS:
      Changes in vasomotion and capillary density were determined by LDF and capillary
      videomicroscopy in skin, respectively, before and during a hyperinsulinemic
      euglycemic clamp in 19 healthy volunteers. RESULTS: Insulin-induced increase in
      the neurogenic vasomotion domain was positively related to insulin-augmented
      capillary recruitment (r = 0.51, p = 0.04), and both parameters were related to
      insulin-mediated glucose uptake (r = 0.47, p = 0.06 and r = 0.73, p = 0.001,
      respectively). The change in insulin-augmented capillary recruitment could, at
      least statistically, largely explain the association between the neurogenic
      domain and insulin-mediated glucose uptake. CONCLUSIONS: Insulin-induced changes
      in vasomotion and capillary recruitment are associated in healthy volunteers.
      These data suggest that insulin's action to recruit capillaries may in part
      involve action on the neurogenic vasomotion domain, thereby enhancing capillary
      perfusion and glucose uptake.

PMID- 24444139
TI  - Peripheral chemoreceptor responsiveness and hypoxic pulmonary vasoconstriction in
      humans.
AB  - OBJECTIVE: Studies in animals have shown that interruption of carotid body
      afferent hypoxic signaling or efferent CNS activity to the lung enhances hypoxic
      pulmonary vasoconstriction (HPV). Whether a similar influence of the CNS on HPV
      strength is present in humans has never been studied, owing to the invasive
      nature of physical neural ablation or nonspecific systemic effects of
      pharmacological blockade of putative neural pathways. In order to demonstrate a
      peripheral chemoreceptor-mediated modulation of HPV in man, we hypothesized that
      individuals with high hypoxic ventilatory responsiveness, indicative of strong
      peripheral hypoxic chemosensitivity, should have less HPV in response to inspired
      hypoxia. METHODS: In 15 healthy men and women, we measured the normobaric
      poikilocapnic hypoxic ventilatory response (HVR; L min(-1) % SPo2(-1)) during 15
      min of hypoxia (FIo2=0.12). On the following day, we then measured pulmonary
      artery systolic pressure (PASP) using echosonography while subjects randomly
      breathed 0.21, 0.18, 0.15, and 0.12 FIo2, each for periods of 15 min. We chose
      this strategy to obtain an equivalent stimulus for HPV in all subjects, using
      SPo2 as a surrogate for alveolar Po2. HPV was assessed as PASP at a common
      interpolated arterial oxygen saturation (SPo2) of 85%. RESULTS: We recorded a
      sufficient six-fold range of HVR (0.05-0.30, mean 0.13 L min(-1) % SPo2(-1))
      similar to previously published data on normobaric, poikilocapnic HVR. HPV at
      SPo2 of 85% was 28.5 mmHg (range 21.7-41.3). There was a significant inverse
      relationship between poikilocapnic HVR and HPV (p=0.006, R(2)=0.38). DISCUSSION:
      Previous studies of individuals with susceptibility to high altitude pulmonary
      edema (HAPE) have suggested that both low HVR and high HPV are important risk
      factors. We show that these two responses are inversely correlated and conclude
      that a greater magnitude of peripheral chemoreceptor response to hypoxia limits
      hypoxic pulmonary vasoconstriction in healthy subjects.

PMID- 24444140
TI  - Psychotherapy versus usual care in pediatric migraine and tension-type headache:
      a single-blind controlled pilot study.
AB  - BACKGROUND: Despite growing interest in psychotherapy in child and adolescent
      headache, efficacy studies in this research field have focused mainly on
      cognitive-behavioral therapies. Whereas relaxation and cognitive-behavioral
      techniques, in particular, have been found to reduce the intensity and frequency
      of headache in children and adolescents, data on psychodynamic psychotherapy in
      this population are lacking.Our aim was to explore the effectiveness of a brief
      psychodynamic psychotherapy program in the treatment of idiopathic headache in
      childhood and adolescence. METHODS: Thirty-three newly diagnosed idiopathic
      headache sufferers aged 6-18 years, consecutively referred to our outpatient
      services, were randomized to receive either a brief cycle of psychodynamic
      psychotherapy (eight sessions administered at two-week intervals) or usual care
      (clinical interview, neurological examination, counselling, symptomatic
      therapy).The two groups were evaluated at baseline (T0) and at six months (T1) to
      be assessed for headache characteristics (i.e. frequency, intensity and
      duration), quality of life (i.e. the EuroQoL score), patient's global health
      status (i.e. the Clinical Global Impression score), and emotional-behavioral
      symptoms (i.e. Child Behavior Checklist scores). RESULTS: The two groups were
      fairly similar with reference to the main demographic and clinical variables. The
      T0/T1 comparison showed a statistically significant improvement in headache
      frequency (p = 0.005), intensity (p < 0.001) and duration (p = 0.002), a
      statistically significant improvement in the CGI score (p = 0.018), and a
      borderline improvement in the EuroQoL score (p = 0.053) in the group receiving
      psychotherapy. CONCLUSIONS: According to our pilot findings, a brief
      psychodynamic psychotherapy program may be more effective than usual care in
      children and adolescents with idiopathic headache.

PMID- 24444141
TI  - Delayed appendectomy versus early appendectomy in the treatment of acute
      appendicitis: a retrospective study.
AB  - BACKGROUND: The controversy still exists about the timing of operation for
      appendicitis. The aim of this study was to compare the outcomes between early
      appendectomy and delayed appendectomy and assess the feasibility of delayed
      operation. METHODS: The medical records of patients with acute appendicitis who
      received operation between January 1, 2011 and December 31, 2011, were
      retrospectively reviewed. Outcome measures were white blood cell (WBC) count at
      postoperative first day, time to soft diet, complication rate, surgical site
      infection (SSI) rate, length of hospital stay, and readmission within 30 days.
      RESULTS: During the study period, a total of 478 patients underwent
      appendectomies, and 145 patients were excluded, leaving 333 who met inclusion
      criteria. Based on the time from arrival at hospital to incision, they were
      divided into two groups: 177 (53.2%) in group A and 156 (46.8%) in group B. There
      were no significant differences in preoperative demographics and clinical data
      between two groups. The mean WBC count at postoperative first day of group B were
      lower than that of group A (p = 0.0039). There were no significant differences in
      time to soft diet, length of postoperative hospital stay, complication rate, and
      readmission rate between two groups. SSI including intra-abdominal abscess was
      also shown no significant difference (Group A, 1.7% and Group B, 3.9%; p =
      0.3143). CONCLUSIONS: This study revealed that delayed appendectomy was safe and
      feasible for adult patient although the clinical outcomes of delayed appendectomy
      were not superior to those of early appendectomy. We suggest that surgeons would
      decide the appropriate timing of appendectomy with consideration other situations
      such as available hospital resources.

PMID- 24444143
TI  - A fuzzy-atom analysis of electron delocalization on hydrogen bonds.
AB  - The extent of electron delocalization is quantified for set of cyclic complexes
      exhibiting two or more hydrogen bonds (HBs). In particular, the delocalization
      index (DI) between the atoms directly involved in the HB, and the ING (a
      normalized n-center delocalization index) have been evaluated using several fuzzy
      atom schemes, namely Becke, Becke-rho, Hirshfeld, and Hirshfeld-Iterative. The
      results have been compared with the widely used Quantum Theory of Atoms in
      Molecules (QTAIM) atomic definition. The DI values are found to correlate very
      well with geometrical or topological descriptors widely used in the literature to
      characterize HB systems. Among all fuzzy-atom methods, the ones that can better
      accommodate the different partial ionic character of the bonds perform
      particularly well. The best performing fuzzy-atom scheme for both pairwise and n
      center electron delocalization is found to be the Becke-rho method, for which
      similar results to QTAIM model are obtained with a much reduced computational
      cost. These results open up a wide range of applications of such electron
      delocalization descriptors based on fuzzy-atoms for noncovalent interactions in
      more complex and larger systems. 

PMID- 24444142
TI  - Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia
      in a rat strain artificially selected and bred for low aerobic running capacity.
AB  - AIM: Rats selectively bred for inborn low capacity of running (LCR) display a
      series of poor health indices, whereas rats selected for high capacity of running
      (HCR) display a healthy profile. We hypothesized that selection of low aerobic
      capacity over generations leads to a phenotype with increased diastolic Ca(2+)
      leak that trigger arrhythmia. METHODS: We used rats selected for HCR (N = 10) or
      LCR (N = 10) to determine the effect of inborn aerobic capacity on Ca(2+) leak
      and susceptibility of ventricular arrhythmia. We studied isolated Fura-2/AM
      loaded cardiomyocytes to detect Ca(2+) handling and function on an inverted
      epifluorescence microscope. To determine arrhythmogenicity, we did a final
      experiment with electrical burst pacing in Langendorff-perfused hearts. RESULTS:
      Ca(2+) handling was impaired by reduced Ca(2+) amplitude, prolonged time to 50%
      Ca(2+) decay and reduced sarcoplasmic reticulum (SR) Ca(2+) content. Impaired
      Ca(2+) removal was influenced by reduced SR Ca(2+) ATP-ase 2a (SERCA2a) function
      and increased sodium/Ca(2+) exchanger (NCX) in LCR rats. Diastolic Ca(2) leak was
      87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression
      levels of phosphorylated threonine 286 CaMKII levels and increased RyR2
      phosphorylation at the serine 2814 site mechanistically support our findings of
      increased leak in LCR. LCR rats had significantly higher incidence of ventricular
      fibrillation. CONCLUSION: Selection of inborn low aerobic capacity over
      generations leads to a phenotype with increased risk of ventricular fibrillation.
      Increased phosphorylation of CaMKII at serine 2814 at the cardiac ryanodine
      receptor appears as an important mechanism of impaired Ca(2+) handling and
      diastolic Ca(2+) leak that results in increased susceptibility to ventricular
      fibrillation.

PMID- 24444144
TI  - Cost-effectiveness comparison of renal calculi treated with ureteroscopic laser
      lithotripsy versus shockwave lithotripsy.
AB  - PURPOSE: To evaluate the cost-effectiveness of shockwave lithotripsy (SWL) vs
      ureteroscopic lithotripsy (URS) for patients with renal stones <1.5 cm in
      diameter. METHODS: Patient age, stone diameter, stone location, and stone-free
      status were recorded for patients treated with SWL or URS for renal stones <1.5
      cm in maximal diameter over a 1-year period. Institutional charges were obtained
      from in-house billing. A decision analysis model was constructed to compare the
      cost-effectiveness of SWL and URS and using our results and success rates for
      modeling. Three separate models were created to reflect practice patterns for
      SWL. RESULTS: One hundred fifty-eight patients were included in the study-78
      underwent SWL and 80 underwent URS as primary treatment. Single procedure stone
      free rates (SFR) for SWL and URS were 55% and 95%, respectively (P<0.0001).
      Decision analysis modeling demonstrated cost-effectiveness of SWL when SWL single
      procedure SFR were 65% to 67% or when URS single procedure SFR was 72% to 84%.
      CONCLUSIONS: This retrospective study revealed superior SFR results for renal
      stones <1.5 cm for URS compared with SWL. Our decision analysis model
      demonstrates that for SWL SFR less than 65% to 67% or for URS SFR greater than
      72% to 84%, SWL is not a cost-effective treatment option. Based on these
      findings, careful stratification and selection of stone patients may enable
      surgeons to increase the cost-effectiveness of SWL.

PMID- 24444145
TI  - Foreword.

PMID- 24444148
TI  - Accurate nitric oxide measurements from donors in cell media: identification of
      scavenging agents.
AB  - Nitric oxide (NO) is an essential messenger in human physiology, mediating
      cellular processes ranging from proliferation to apoptosis. The effects of NO are
      concentration dependent, and control over the instantaneous amount of NO
      available to cells is essential for determining the therapeutic NO dosages for
      various applications. As such, the development of NO therapeutic materials relies
      on accurate quantitative NO measurements that provide both total NO release from
      the NO donor as well as instantaneous NO concentrations. On the basis of the
      complexity of the cell media environment, inaccurate NO reporting often occurs
      for in vitro studies. These inaccuracies result from using inert media such as
      phosphate buffer saline (PBS), failing to account for the reactivity of media
      components. In this work, we describe a method for directly quantifying the
      instantaneous and total amounts of NO from commonly used NO donors in
      commercially available cell media routinely used for endothelial and neural cell
      lines. A riboflavin-tryptophan complex found in the media was identified as the
      major scavenger of NO in the cell media and likely reacts with NO via a radical
      radical reaction. This finding significantly impacts the amount of available NO.
      The scavenging effects are concentration dependent on the riboflavin-tryptophan
      complex and the NO release rate from the NO donor. The results of this study
      provide insights on the exogenous amounts of NO that are present in cell media
      and may provide an explanation for differences in NO dosages between buffer
      experiments and in vitro and in vivo studies. 

PMID- 24444147
TI  - The centella asiatica juice effects on DNA damage, apoptosis and gene expression
      in hepatocellular carcinoma (HCC).
AB  - BACKGROUND: This paper is to investigate the effects of Centella asiatica on
      HepG2 (human hepatocellular liver carcinoma cell line). Centella asiatica is
      native to the Southeast Asia that is used as a traditional medicine. This study
      aims to determine the chemopreventive effects of the Centella asiatica juice on
      human HepG2 cell line. METHODS: Different methods including flow cytometry, comet
      assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to
      show the effects of juice exposure on the level of DNA damage and the reduction
      of cancerous cells. MTT assay is a colorimetric method applied to measure the
      toxic effects of juice on cells. RESULTS: The Centella asiatica juice was not
      toxic to normal cells. It showed cytotoxic effects on tumor cells in a dose
      dependent manner. Apoptosis in cells was started after being exposed for 72 hr of
      dose dependent. It was found that the higher percentage of apoptotic cell death
      and DNA damage was at the concentration above 0.1%. In addition, the juice
      exposure caused the reduction of c-myc gene expression and the enhancement of c
      fos and c-erbB2 gene expressions in tumor cells. CONCLUSIONS: It was concluded
      that the Centella asiatica juice reduced liver tumor cells. Thus, it has the
      potential to be used as a chemopreventive agent to prevent and treat liver
      cancer.

PMID- 24444146
TI  - Poly(ADP-ribose) polymerase inhibition with HYDAMTIQ reduces allergen-induced
      asthma-like reaction, bronchial hyper-reactivity and airway remodelling.
AB  - Activation of poly(ADP-ribose) polymerases (PARPs) is considered a key event in
      the molecular and cellular processes leading from acute asthma attacks to
      bronchial hyper-reactivity, leucocyte recruitment, chronic inflammation, airway
      remodelling and lung damage. The present investigation has been carried out to
      investigate the action of hydroxyl-dimethylaminomethyl-thieno[2,3-c]isoquinolin
      5(4H)-one (HYDAMTIQ), a new potent PARP inhibitor, in the process leading from
      asthma-like events to airway damage. Ovalbumin-sensitized guinea pigs exposed two
      times to allergen inhalation were treated for 8 days with vehicle or HYDAMTIQ.
      Asthma-like signs, bronchial hyper-reactivity to methacholine, cytokine
      production, histamine release from mast cells, airway remodelling, collagen
      deposition and lung damage were evaluated. Repeated HYDAMTIQ administration (1-10
      mg/kg/day i.p.) reduced lung PARP activity, delayed the appearance and reduced
      the severity of allergen-induced cough and dyspnoea and dampened the increased
      bronchial responses to methacholine. HYDAMTIQ-treated animals presented reduced
      bronchial or alveolar abnormalities, lower number of eosinophils and other
      leucocytes in the lung and decreased smooth muscle or goblet cell hyperplasia.
      The treatment also reduced lung oxidative stress markers, such as malondialdehyde
      or 8-hydroxy-2'-deoxyguanosine and the lung content of pro-inflammatory cytokines
      (TNF-alpha, interleukin (IL)-1beta, IL-5, IL-6 and IL-18). Finally, mast cells
      isolated from the peritoneal or pleural cavities of sensitized, HYDAMTIQ-treated
      animals had a reduced ability to release histamine when exposed to ovalbumin in
      vitro. Our findings support the proposal that PARP inhibitors could have a
      therapeutic potential to reduce chronic lung inflammation, airway damage and
      remodelling in severe unresponsive asthmatic patients.

PMID- 24444149
TI  - Recent contributions of elastin-like recombinamers to biomedicine and
      nanotechnology.
AB  - The emergence of the new scientific field known as nanomedicine is being
      catalyzed by multiple improvements in nanoscience techniques and significant
      progress in materials science, especially as regards the testing of novel and
      sophisticated biomaterials. This conjuncture has furthered the development of
      promising instruments in terms of detection, bioanalysis, therapy, diagnostics
      and imaging. Some of the most innovative new biomaterials are protein-inspired
      biomimetic materials in which modern biotechnology and genetic-engineering
      techniques complement the huge amount of information afforded by natural protein
      evolution to create advanced and tailor-made multifunctional molecules. Amongst
      these protein-based biomaterials, Elastin-like Recombinamers (ELRs) have
      demonstrated their enormous potential in the fields of biomedicine and
      nanoscience in the last few years. This broad applicability derives from their
      unmatched properties, particularly their recombinant and tailor-made nature, the
      intrinsic characteristics derived from their elastin-based origin (mainly their
      mechanical properties and ability to self-assemble as a result of their stimuli
      responsive behavior), their proven biocompatibility and biodegradability, as well
      as their versatility as regards incorporating advanced chemical or recombinant
      modifications into the original structure that open up an almost unlimited number
      of multifunctional possibilities in this developing field. This article provides
      an updated review of the recent challenges overcome by using these recombinant
      biomaterials in the fields of nano- and biomedicine, ranging from nanoscale
      applications in surface modifications and self-assembled nanostructures to drug
      delivery and regenerative medicine. 

PMID- 24444150
TI  - Functional poly(epsilon-caprolactone) based materials: preparation, self-assembly
      and application in drug delivery.
AB  - Recent advances in synthesis of functional poly-epsilon-caprolactone (PCL) and
      its self-assembly behavior, as well as application in drug delivery have been
      reviewed. Three strategies including end group functionalization,
      postpolymerization modification and new monomer preparation have been summarized
      to show possibilities for PCL derivatives. Complex architectures like cyclic and
      multi-arm PCL have been emphasized. Both chemical composition and topology have
      coordinately affected the property of PCL-based materials on the molecular level.
      A large variety of PCLs with sophisticated topology like block, graft, cyclic,
      and star have displayed versatile morphologies in solutions. These selfassembly
      aggregates have been applied as nano-scaled drug carries either to physically
      encapsulate or covalently conjugate drugs for controlled release. In particular,
      PCL with pendant groups has been extensively studied to illustrate the
      noncovalent interaction with drugs and the influence on the release profile. In
      general, functional PCL has shown great potential in construct of complicated
      supramolecular structures, and thus as ideal drug carriers for sustainable and
      targeted delivery. 

PMID- 24444151
TI  - Formation and morphology of reverse micelles formed by nonionic surfactants in
      "dry" organic solvents.
AB  - The formation of reverse micelles by nonionic alcohol ethoxylates surfactants in
      two "dry" non polar solvents, heptane and dibutoxymethane (DBM), has been
      studied. These surfactants are formed by a linear hydrocarbon chain consisting of
      i carbons, and a poly(ethylene oxide) chain with j ethoxylate units (EO) ending
      with a hydroxyl group, CiEOj. The study is focused on the determination of the
      critical micelle concentration CMC and the size and morphology of the formed
      aggregates. The CMC was obtained from the decreasing of interfacial tension with
      increasing surfactant concentration and by using pyrene sulfonic acid sodium salt
      as fluorescence probe. The results show that the CMC in heptane is one order of
      magnitude higher than in DBM and two orders of magnitude higher than those
      determined in aqueous solution. The self-diffusion coefficients D of C8EO5, C8EO4
      and C10EO6 in heptane, were obtained by diffusion ordered spectroscopy (DOSY (1)H
      NMR). The experimental values of D were then fitted to four different
      configurations to determine the most probable morphology of the formed
      aggregates. In all cases the presence of large and compact aggregates, with
      aggregation numbers going from a few dozens of monomers to a hundred of them, was
      shown. 

PMID- 24444152
TI  - Reversible DNA compaction.
AB  - In this review we summarize and discuss the different methods we can use to
      achieve reversible DNA compaction in vitro. Reversible DNA compaction is a
      natural process that occurs in living cells and viruses. As a result these
      process long sequences of DNA can be concentrated in a small volume (compacted)
      to be decompacted only when the information carried by the DNA is needed. In the
      current work we review the main artificial compacting agents looking at their
      suitability for decompaction. The different approaches used for decompaction are
      strongly influenced by the nature of the compacting agent that determines the
      mechanism of compaction. We focus our discussion on two main artificial
      compacting agents: multivalent cations and cationic surfactants that are the best
      known compacting agents. The reversibility of the process can be achieved by
      adding chemicals like divalent cations, alcohols, anionic surfactants,
      cyclodextrins or by changing the chemical nature of the compacting agents via pH
      modifications, light induced conformation changes or by redox-reactions. We
      stress the relevance of electrostatic interactions and self-assembly as a main
      approach in order to tune up the DNA conformation in order to create an on-off
      switch allowing a transition between coil and compact states. The recent advances
      to control DNA conformation in vitro, by means of molecular self-assembly, result
      in a better understanding of the fundamental aspects involved in the DNA behavior
      in vivo and serve of invaluable inspiration for the development of potential
      biomedical applications. 

PMID- 24444153
TI  - Nano-droplet systems by surfactant self-assembly and applications in the
      pharmaceutical industry.
AB  - Liquid systems containing droplets with size in the nanoscale range are
      attractive from both scientific and technological points of view as they have
      many current and potential applications in several industries and products. The
      formation and stabilization of nano-droplet systems are mostly based on the self
      assembly of surfactant (amphiphilic) molecules at interfaces, driven by the
      solvophobic effect. Surfactants are involved in both top-bottom (high energy) and
      bottom- up (low energy) methods. Several devices have also been developed to aid
      in liquid fragmentation down to the nanometer scale. Nano-droplet systems can be
      both thermodynamically stable (microemulsions) or metastable (nanoemulsions), and
      appropriate formulation is a key for optimum product design in terms of droplet
      size, maximum solubilization, colloidal stability, and optical and rheological
      properties, among others. Such characteristics are determined by molecular
      packing, interfacial curvature, droplet-droplet interactions, film elasticity and
      nature of the dispersed and continuous phase. These properties can be engineered
      by proper understanding of the molecular structure and phase behavior of the
      multicomponent systems involved and by a range of experimental characterization
      techniques. Nano-droplet systems can help to solve specific issues in
      pharmaceutical products such as processing, limitations in drug solubility or
      stability, control on drug release, drug targeting and absorption; there are many
      examples to prove that. However, several practical aspects should be considered
      for preclinical and clinical tests and product development. 

PMID- 24444154
TI  - Peptide self-assembly: from toxins to amyloid fibrils and nanotubes.
AB  - The process of self-assembly is universal and lies at the heart of biological
      structures and function. Peptide aggregation, while considered a nuisance in
      peptide chemistry, soon gained interest with the discovery of pore-forming
      peptide toxins and had been an area of intense research during last century and
      even to date. This has also resulted in the increasing use of the more
      respectable term peptide self-assembly. The discovery of amyloid forming peptides
      has rekindled the interest in peptide self-assembly since such aggregates are
      directly implicated in many debilitating diseases in human and animals. Amyloid
      aggregates have posed many fundamental questions to researchers. In addition,
      self-assembly of peptides has emerged as a bottom-up strategy for the fabrication
      of nanostructures owing to highly ordered nature of the process and considerable
      degree of flexibility and diversity provided by peptides as starting materials.
      This review provides a brief account of the progress in the field of peptide self
      assembly from pore-forming toxins to amyloid forming peptides and those forming
      nanostructures. 

PMID- 24444155
TI  - Understanding recognition and self-assembly in biology using the chemist's
      toolbox. Insight into medicinal chemistry.
AB  - Medicinal chemistry is intimately connected with basic science such as organic
      synthesis, chemical biology and biophysical chemistry among other disciplines.
      The reason of such connections is due to the power of organic synthesis to
      provide designed molecules; chemical biology to give tools to discover biological
      and/or pathological pathways and biophysical chemistry which provides the
      techniques to characterize and the theoretical background to understand molecular
      behaviour. The present review provides some selective examples of these research
      areas. Initially, template dsDNA organic synthesis and the spatio-temporal
      control of transcription are presenting following by the supramolecular entities
      used in drug delivery, such as liposomes and liquid crystal among others.
      Finally, peptides and protein self-assembly is connected with biomaterials and as
      an important event in the balance between health and disease. The final aim of
      the present review is to show the power of chemical tools not only for the
      synthesis of new molecules but also to improve our understanding of recognition
      and self-assembly in the biological context. 

PMID- 24444156
TI  - Mechanisms of fibrinogen adsorption at solid substrates.
AB  - The aim of this work was to critically review recent results pertinent to
      fibrinogen adsorption at solid/electrolyte interfaces with the emphasis focused
      on a quantitative analysis of these processes in terms of the electrostatic
      interactions. Accordingly, in the first part, the primary chemical structure of
      fibrinogen is analyzed. Physicochemical data pertinent to the bulk properties
      derived from hydrodynamic, dynamic light scattering and micro-electrophoretic
      measurements aided by theoretical modeling are discussed. Possible conformations
      and the effective charge distribution over the fibrinogen molecule for various pH
      an ionic strength are defined, especially the semi-collapsed conformation
      prevailing at physiological conditions. Adsorption kinetics of fibrinogen at
      hydrophilic and hydrophobic (polymer modified) substrates determined by various
      techniques is described. Adsorption at polymeric carrier particles, pertinent to
      immunological assays, studied in terms of electrokinetic and concentration
      depletion methods, are also considered. The reversibility of adsorption,
      fibrinogen molecule orientations and maximum coverages are thoroughly discussed.
      The stability of fibrinogen monolayers formed at these carrier particles in
      respect to pH and ionic strength cyclic changes is also discussed. In the final
      section interactions and deposition of model colloid particles on fibrinogen
      monolayers are analyzed which allows one to derive valuable information about
      molecule orientations. Based on the physicochemical data, adsorption kinetics and
      colloid particle deposition measurements, probable adsorption mechanisms of
      fibrinogen on solid/electrolyte interfaces are defined. 

PMID- 24444157
TI  - Interaction and cytotoxic effects of hydrophobized chitosan nanoparticles on MDA
      MB-231, HeLa and Arpe-19 cell lines.
AB  - In this work, we investigate the effect of chitosan hydrophobization on the
      internalization and cytotoxic effect of chitosan-based nanoparticles (NPs) on
      breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa) and noncancer
      cells (Arpe-19). We also analyzed the interaction of NPs with a phospholipid
      (DPPC) membrane model at the airwater interface. An alkylation procedure to
      insert 8 carbon chains along the chitosan macromolecule with final 10 and 30 %
      substitution degrees was used. Nuclear magnetic resonance (NMR) and infrared
      spectroscopes (IR) were used to evaluate the success and extent of the
      hydrophobization procedure. Size, shape, and charge of NPs were evaluated by
      dynamic light scattering (DLS), atomic force microscope (AFM), and zeta
      potential, respectively. The effect of hydrophobicity on NPs was the reduction of
      the NPs average size, the formation of slightly elongated structures and the
      enhancing of the interaction of NPs with a DPPC monolayer at the air-water
      interface. By using fluorescence images on fluorescein-chitosan NPs, we observed
      a higher internalization of hydrophobic chitosan NPs in cancer cells in
      comparison with a low internalization of these NPs in normal cells. Even when non
      modified chitosan NPs were highly internalized in all cell lines, hydrophobized
      chitosan NPs showed a significantly higher cytotoxic effect on cancer cells in
      comparison with a lower effect showed by non-modified chitosan NPs on these
      cells. The cytotoxic effect on the normal cell line used was low for native
      chitosan NPs and negligible for hydrophobized chitosan NPs. 

PMID- 24444158
TI  - Editorial: nanosystems: an innovative tools for medicinal chemistry.

PMID- 24444159
TI  - Flow chemistry to control the synthesis of nano and microparticles for biomedical
      applications.
AB  - In this article we review the flow chemistry methodologies for the controlled
      synthesis of different kind of nano and microparticles for biomedical
      applications. Injection mechanism has emerged as new alternative for the
      synthesis of nanoparticles due to this strategy allows achieving superior levels
      of control of self-assemblies, leading to higher-ordered structures and rapid
      chemical reactions. Self-assembly events are strongly dependent on factors such
      as the local concentration of reagents, the mixing rates, and the shear forces,
      which can be finely tuned, as an example, in a microfluidic device. Injection
      methods have also proved to be optimal to elaborate microsystems comprising
      polymer solutions. Concretely, extrusion based methods can provide controlled
      fluid transport, rapid chemical reactions, and cost-saving advantages over
      conventional reactors. We provide an update of synthesis of nano and
      microparticles such as core/shell, Janus, nanocrystals, liposomes, and
      biopolymeric microgels through flow chemistry, its potential bioapplications and
      future challenges in this field are discussed. 

PMID- 24444160
TI  - Nanoparticles vs cancer: a multifuncional tool.
AB  - Nanotechnology is revolutionizing the development of different branches of
      science. The investigation of nanomaterials in the battle against cancer is not
      an exception. The main goal of this contribution is to bring an overview about
      the types of organic and inorganic nanomaterials that are under investigation for
      its applications in different aspects of cancer therapy: detection, diagnosis,
      contrast agents, controlled drug delivery, and hyperthermia. This review also
      includes fundamental aspects such as basic properties and synthesis of
      nanoparticles, with an emphasis on the use of selfassembed systems such as
      micelles, microemulsions, nanoemulsions, and liposomes. 

PMID- 24444161
TI  - Cationic lipids as transfecting agents of DNA in gene therapy.
AB  - The use of cationic lipids (CLs) as transfecting agents of DNA has received an
      increasing attention in the last two decades. In order to improve the
      transfection efficiency with lower cytotoxicity, many CLs have been synthesized
      to be used as non-viral vectors, not only of DNA but also for other nucleic
      acids. Cationic lipids together with a helper lipid form mixed liposomes that
      compact DNA forming lipoplexes, gene vectors able to transport DNA into the cells
      without provoke an immune response. This review is focused in the progress and
      recent advances experimented in this area, mainly during last decade. Special
      attention has been paid: (a) to the biophysical characterization (electrostatics,
      structure, size and morphology) of the lipoplexes using a wide variety of
      experimental methods and, (b) to the biological studies (transfection efficiency
      and cell viability/cytotoxicity) addressed to confirm the viability and the
      optimum formulations of these DNA vectors to be used in gene therapy. Finally,
      and in order to take advantage towards a rational design of improved lipid gene
      vectors, the lipoplex structure-biological activity relationship has been also
      reviewed. 

PMID- 24444162
TI  - Human fibrinogen adsorption on latex particles at pH 7.4 studied by
      electrophoretic mobility and AFM measurements.
AB  - Human fibrinogen adsorption on negatively charged latex particles was
      investigated using the electrophoretic and the concentration depletion methods.
      Measurements were conducted at pH 7.4 and in the range of ionic strength of 10(
      3) - 0.15 M NaCl. Firstly, the bulk physicochemical properties of fibrinogen were
      characterized. The zeta potential and the uncompensated (electrokinetic) charges
      of the protein were determined from the electrophoretic measurements. Next,
      systematic experiments were performed to determine the dependencies of the
      electrophoretic mobility of latex on the amount of adsorbed protein.
      Electrophoretic mobility increased significantly upon fibrinogen adsorption that
      was proven irreversible. The maximum coverage of fibrinogen on latex particles
      determined via the concentration depletion method varied between 1.9 mg m(-2) and
      3.2 mg m(-2) for 10(-3) and 0.15 M NaCl, respectively. The changes in the maximum
      coverage were interpreted as due to electrostatic repulsion among adsorbed
      protein molecules. Additionally, the stability of latex covered by fibrinogen was
      determined. It was proven that cyclic changes of ionic strength from 10(-3) to
      0.15 M NaCl did not change the electrophoretic mobility. Based on these
      observations, it was concluded that there were no conformational changes within
      adsorbed fibrinogen molecules. The experimental data, allowed one to elaborate a
      robust procedure of preparing latex particles covered by fibrinogen of designed
      coverage and molecule distribution. 

PMID- 24444163
TI  - Transition from fractal to spherical aggregates of globular proteins: Brownian
      like activation and/or hydrodynamic stress?
AB  - We report on the structure of whey protein aggregates formed by a short heating
      coupled to shear at high temperatures (80-120) and neutral pH in scale-up
      processing conditions, using gel filtration chromatography, light scattering,
      small angle neutron scattering, and cryogenic transmission electron microscopy.
      The results are interpreted in terms of coexistence of residual non-aggregated
      proteins and aggregates. The characteristics of aggregates such as the size, the
      aggregation number and the shape evidence two different morphologies. Whereas
      aggregates formed at 80  degrees C show a selfsimilar structure down to a length
      scale of the monomer with a fractal dimension typical for reaction limited
      cluster aggregation (D~2.2), aggregates formed at higher temperature show a
      spherical morphology, with the structure from small angle neutron scattering data
      best modelled with the form factor of a polydisperse sphere. We compare the
      structure of these aggregates to that of aggregates formed in quiescent
      conditions at lab scale. The structure transition is interpreted in terms of a
      non-trivial interplay between three perturbation factors: interparticle
      interaction, temperature and shear. 

PMID- 24444164
TI  - Cell adhesion response on femtosecond laser initiated liquid assisted silicon
      surface.
AB  - Silicon substrates were irradiated at normal incidence with a femtosecond
      Ti:sapphire laser (Quatronix, 90 fs pulse duration, 1 kHz repetition rate, M(2) ~
      1.2, maximum energy peak 350 mJ ) operating at a wavelength of 400 nm and focused
      via a microscope objective (Newport; UV Objective Model, 37x 0.11 N.A.). The
      laser scanning was assisted by liquids precursors media such as methanol and
      1,1,2-trichlorotrifluoroethane. By altering the processing parameters, such as
      incident laser energy, scanning speed, and different irradiation media, various
      surface structures were produced on areas with 1 mm(2) dimensions. We analyzed
      the dependence of the surface morphology on laser pulse energy, scanning speed
      and irradiation media. Well ordered areas are developed without imposing any
      boundary conditions for the capillary waves that coarsens the ripple pattern. To
      assess biomaterial-driven cell adhesion response we investigated actin filaments
      organization and cell morphological changes following growth onto processed
      silicon substrates. Our study of bone cell progenitor interaction with laser
      nanoprocessed silicon lines has shown that cells anchor mainly to contact points
      along the nanostructured surface. Consequently, actin filaments are stretched
      towards the 15 um wide parallel lines increasing lateral cell spreading and
      changing the bipolar shape of mesenchymal stem cells. 

PMID- 24444165
TI  - Simulation modeling of supported lipid membranes - a review.
AB  - Lipid membranes are of great importance for many biological systems and
      biotechnological applications. One method to gain a profound understanding of the
      dynamics in lipid membranes and their interaction with other system components is
      by modeling these systems by computer simulations. Many different approaches have
      been undertaken in this endeavor that have led to molecular level insights into
      the underlying mechanisms of several experimental observations and biological
      processes with an extremely high temporal resolution. As compared to the free
      standing lipid bilayers, there are fewer simulation studies addressing the
      systems of supported lipid membranes. Nevertheless, these have significantly
      enhanced our understanding of the behavior of lipid layers employed in
      applications spanning from biosensors to drug delivery and for biological
      processes such as the breathing cycle of lung surfactants. In this review, we
      give an account of the state of the art of methods and applications of the
      simulations of supported lipid bilayers, interfacial membranes at the air/water
      interface and on solid surfaces. 

PMID- 24444166
TI  - Assembled core-shell nanostructures of gold nanoparticles with biocompatible
      polymers toward biology.
AB  - The present review focuses on core-shell nanostructures of spherical gold
      nanoparticles (Au NPs) and biocompatible polymers mainly from the view points of
      preparation approaches, nanocomposite properties and potential applications for
      biology. The preparation approaches are assorted into direct-reduction, covalent
      "graft-to", "graft-from" approach, surface bonding and physical adsorption.
      Various biocompatible polymers are involved such as the thermosensitive polymers,
      pH-responsive polymers, antibiofouling polymers, conductive polymers and several
      natural polymers. The encapsulating and loading properties, cellular uptake and
      drug release control, as well as biorecognition, targeting and sensing potential
      are discussed in connection with biological systems. These polymeric gold
      nanocomposites will have a great potential in biotechnology and life science but
      also face enormous challenge in future applications. 

PMID- 24444167
TI  - Magnetic hyperthermia with magnetic nanoparticles: a status review.
AB  - Recent advances in development of potential magnetic nanoparticles for magnetic
      fluid hyperthermia are summarized. This review covers relation between various
      size dependent physical properties and their applications subject to modification
      in synthesis methods. Brief discussion on different heating mechanism of magnetic
      nanoparticles is provided. This review covers recent progress of various magnetic
      nanoparticles including core shell type for in vitro, in vivo and pre-clinical
      trials. The highlight of this review is to build up a bridge between synthesis,
      surface modification and in vivo- pre-clinical in magnetic fluid hyperthermia. 

PMID- 24444168
TI  - Self-assembly drugs: from micelles to nanomedicine.
AB  - Self-assembly has fascinated many scientists over the past few decades. Rapid
      advances and widespread interest in the study of this subject has led to the
      synthesis of an ever-increasing number of elegant and intricate functional
      structures with sizes that approach nano- and mesoscopic dimensions. Today, it
      has grown into a mature field of modern science whose interfaces with many
      disciplines have provided invaluable opportunities for crossing boundaries for
      scientists seeking to design novel molecular materials exhibiting unusual
      properties, and for researchers investigating the structure and function of
      biomolecules. Consequently, self-assembly transcends the traditional divisional
      boundaries of science and represents a highly interdisciplinary field including
      nanotechnology and nanomedicine. Basically, self-assembly focuses on a wide range
      of discrete molecules or molecular assemblies and uses physical transformations
      to achieve its goals. In this Review, we present a comprehensive overview of the
      advances in the field of drug self-assembly and discuss in detail the synthesis,
      self-assembly behavior, and physical properties as well as applications. We refer
      the reader to past reviews dealing with colloidal molecules and colloidal self
      assembly. In the first part, we will discuss, compare, and link the various
      bioinformatic procedures: Molecular Dynamics and Quantitative Structure Activity
      Relationship. The second section deals with the self-assembly behavior in more
      detail, in which we focus on several experimental techniques, selected according
      to the depth of knowledge obtained. The last part will review the advances in
      drug-protein assembly. Nature provides many examples of proteins that form their
      substrate binding sites by bringing together the component pieces in a process of
      self-assembly. We will focus in the understanding of physical properties and
      applications developing thereof. 

PMID- 24444169
TI  - Theoretical & experimental study of self-assembled systems in medicinal
      chemistry: applications from bio-physics, bio-materials, and nano sciences.

PMID- 24444170
TI  - Facial expression recognition and emotion understanding in children after
      neonatal open-heart surgery for transposition of the great arteries.
AB  - AIM: Theory of mind impairments are part of the cognitive morbidities associated
      with transposition of the great arteries (TGA). We sought to assess core
      components of social cognition in school-aged children with TGA. METHOD: Thirty
      eight children with neonatal corrected TGA (27 males, 11 females; mean age 7y
      3mo, SD 1y 2mo) and a comparison group (n=31; 24 males, 7 females; mean age 7y
      4mo, SD 1y 1mo) participated in this study. All children completed measures of
      facial expression recognition, emotion comprehension, and second-order cognitive
      and affective false-belief tasks. The association of medical pre-, intra-, and
      postoperative variables with cognitive outcomes was explored. RESULTS: After
      controlling for potential covariates, children with TGA performed significantly
      less accurately in the mental category of the emotion comprehension battery
      (p=0.002) and on second-order affective false-belief tasks (p<0.05). Preoperative
      variables including an associated ventricular septal defect (p=0.02), a younger
      age at open-heart surgery (p=0.03), and a prenatal diagnosis of TGA (p=0.02) were
      significantly associated with better outcomes. INTERPRETATION: School-aged
      children with TGA display significant impairment on complex affective mental
      state understanding even though facial expression recognition was generally
      preserved. Preoperative factors may be important determinants for long-term
      outcomes after cyanotic congenital heart disease.

PMID- 24444171
TI  - Systematic review with meta-analysis: malignancies with anti-tumour necrosis
      factor-alpha therapy in inflammatory bowel disease.
AB  - BACKGROUND: Anti-tumour necrosis factor-alpha (TNFalpha) antibodies are
      efficacious in inflammatory bowel disease (IBD). These drugs carry the
      theoretical risk of malignancy, particularly lymphoma, but no systematic review
      and meta-analysis has examined this issue. AIM: To pool data from all available
      placebo-controlled studies to estimate risk of malignancy with anti-TNFalpha
      therapy in IBD. METHODS: MEDLINE, EMBASE and the Cochrane central register of
      controlled trials were searched to November 2013. Randomised controlled trials
      (RCTs) comparing anti-TNFalpha therapy with placebo in adults with Crohn's
      disease (CD) or ulcerative colitis (UC) were eligible. Data were pooled to obtain
      a relative risk (RR) of malignancy with a 95% confidence interval (CI). RESULTS:
      The search strategy identified 25,338 citations, of which 22 RCTs were eligible
      (11 infliximab, six adalimumab, four certolizumab and one golimumab) involving
      7054 patients (4566 CD and 2488 UC). In total, there were 16 (0.39%) malignancies
      in 4135 IBD patients allocated to anti-TNFalpha, compared with 13 (0.45%) in 2919
      patients randomised to placebo. There were no cases of lymphoma in the active
      treatment group, compared with three (0.1%) in the control group. The RR of
      malignancy for patients receiving anti-TNFalpha therapy compared with placebo was
      0.77 (95% CI 0.37-1.59). When seven individuals with nonmelanoma skin cancer were
      excluded from the analysis, the RR was 0.90 (95% CI 0.40-2.02). CONCLUSIONS: Anti
      TNFalpha therapy was not associated with an increased risk of malignancy in
      patients with IBD. However, no trials provided data for risk of malignancy beyond
      1 year of treatment, meaning that an increased risk in the longer term cannot be
      excluded.

PMID- 24444172
TI  - The effectiveness of spaced retrieval combined with Montessori-based activities
      in improving the eating ability of residents with dementia.
AB  - AIMS: To explore the long-term effects of standardized and individualized spaced
      retrieval combined with Montessori-based activities on the eating ability of
      residents with dementia. BACKGROUND: Eating difficulty is common in residents
      with dementia, resulting in low food intake, followed by eating dependence,
      weight loss and malnutrition. DESIGN: A single-blinded and quasi-experimental
      design with repeated measures. METHODS: Ninety residents with dementia from four
      veterans' homes in Taiwan took part in this study. The intervention consisted of
      spaced retrieval combined with Montessori-based activities. Twenty-five
      participants in the standardized group received 24 intervention sessions over 8
      weeks. Thirty-eight participants in the individualized group received tailored
      intervention sessions. The number of intervention sessions was adjusted according
      to the participant's recall responses in spaced retrieval. Twenty-seven
      participants in the control group received no treatment. The Chinese version of
      the Edinburgh Feeding Evaluation in Dementia was used, and eating amounts and
      body weight were measured pre-test, posttest and at 1-, 3- and 6-month follow
      ups. Data were collected between July 2008-February 2010. Repeated measures of
      all dependent variables for the three groups were analysed by the linear mixed
      model. RESULTS: The standardized and individualized interventions could
      significantly decrease the scores for the Chinese version of the Edinburgh
      Feeding Evaluation in Dementia and increase the eating amount and body weight
      over time. CONCLUSION: Trained nurses in institutions can schedule the
      standardized or individualized intervention in usual activity time to ameliorate
      eating difficulty and its sequels.

PMID- 24444173
TI  - A longitudinal study of several potential mediators of the relationship between
      child maltreatment and posttraumatic stress disorder symptoms.
AB  - Child maltreatment is a reliable predictor of posttraumatic stress disorder
      (PTSD) symptoms. However, not all maltreated children develop PTSD symptoms,
      suggesting that additional mediating variables explain how certain maltreated
      children develop PTSD symptoms and others do not. The current study tested three
      potential mediators of the relationship between child maltreatment and subsequent
      PTSD symptoms: (a) respiratory sinus arrhythmia reactivity, (b) cortisol
      reactivity, and (c) experiential avoidance, or the unwillingness to experience
      painful private events, such as thoughts and memories. Maltreated (n = 51) and
      nonmaltreated groups (n = 59) completed a stressor paradigm, a measure of
      experiential avoidance, and a semistructured interview of PTSD symptoms. One year
      later, participants were readministered the PTSD symptoms interview. Results of a
      multiple mediator model showed the set of potential mediators mediated the
      relationship between child maltreatment and subsequent PTSD symptoms. However,
      experiential avoidance was the only significant, specific indirect effect,
      demonstrating that maltreated children avoiding painful private events after the
      abuse were more likely to develop a range of PTSD symptoms 1 year later. These
      results highlight the importance of experiential avoidance in the development of
      PTSD symptoms for maltreated children, and implications for secondary prevention
      and clinical intervention models are discussed. 

PMID- 24444174
TI  - Emotion recognition in preschool children: associations with maternal depression
      and early parenting.
AB  - Emotion knowledge in childhood has been shown to predict social functioning and
      psychological well-being, but relatively little is known about parental factors
      that influence its development in early childhood. There is some evidence that
      both parenting behavior and maternal depression are associated with emotion
      recognition, but previous research has only examined these factors independently.
      The current study assessed auditory and visual emotion recognition ability among
      a large sample of preschool children to examine typical emotion recognition
      skills in children of this age, as well as the independent and interactive
      effects of maternal and paternal depression and negative parenting (i.e.,
      hostility and intrusiveness). Results indicated that children were most accurate
      at identifying happy emotional expressions. The lowest accuracy was observed for
      neutral expressions. A significant interaction was found between maternal
      depression and negative parenting behavior: children with a maternal history of
      depression were particularly sensitive to the negative effects of maladaptive
      parenting behavior on emotion recognition ability. No significant effects were
      found for paternal depression. These results highlight the importance of
      examining the effects of multiple interacting factors on children's emotional
      development and provide suggestions for identifying children for targeted
      preventive interventions. 

PMID- 24444175
TI  - Long-term sequelae of subclinical depressive symptoms in early adolescence.
AB  - The long-term sequelae of adolescent depressive symptoms were examined in a
      multimethod, multireporter study of a diverse community sample of 179 adolescents
      followed from age 14 to 24. Mild to moderate levels of early adolescent
      depressive symptoms were found to predict lower maternal relationship quality,
      less positive interactions with romantic partners, and greater loneliness in
      adulthood even after accounting for prior levels of social functioning and for
      concurrent levels of adult depressive symptoms. Predictions were partially
      mediated via late adolescent avoidance of social interactions and poor maternal
      relationship quality. Results are interpreted as suggesting the potential impact
      of depressive symptoms on adolescent social development and the need to consider
      treatment for even mild symptoms and their social concomitants. 

PMID- 24444178
TI  - The first journal on human gene therapy celebrates its 25th anniversary.

PMID- 24444176
TI  - Lasting associations between early-childhood temperament and late-adolescent
      reward-circuitry response to peer feedback.
AB  - Behavioral inhibition, a temperament identifiable in infancy, is associated with
      heightened withdrawal from social encounters. Prior studies raise particular
      interest in the striatum, which responds uniquely to monetary gains in
      behaviorally inhibited children followed into adolescence. Although behavioral
      manifestations of inhibition are expressed primarily in the social domain, it
      remains unclear whether observed striatal alterations to monetary incentives also
      extend to social contexts. In the current study, imaging data were acquired from
      39 participants (17 males, 22 females; ages 16-18 years) characterized since
      infancy on measures of behavioral inhibition. A social evaluation task was used
      to assess neural response to anticipation and receipt of positive and negative
      feedback from novel peers, classified by participants as being of high or low
      interest. As with monetary rewards, striatal response patterns differed during
      both anticipation and receipt of social reward between behaviorally inhibited and
      noninhibited adolescents. The current results, when combined with prior findings,
      suggest that early-life temperament predicts altered striatal response in both
      social and nonsocial contexts and provide support for continuity between
      temperament measured in early childhood and neural response to social signals
      measured in late adolescence and early adulthood. 

PMID- 24444180
TI  - Gene therapy briefs.

PMID- 24444179
TI  - Adenovirus: the first effective in vivo gene delivery vector.

PMID- 24444181
TI  - Off the RAC.

PMID- 24444182
TI  - Historical perspectives pertaining to the NIH Recombinant DNA Advisory Committee.
AB  - Science is host to a constantly emerging series of new paradigms, and it is this
      characteristic that makes science both interesting and dynamic. As a part of this
      continuum, it became possible to create recombinant DNA molecules. Immediately it
      was recognized that there was a potential for serious adverse events associated
      with this new technology. Following two scientific conferences at Asilomar,
      California, the National Institutes of Health moved quickly to create the
      Recombinant DNA Advisory Committee (RAC). For approximately 38 years the RAC has
      served as an open forum for review of various recombinant DNA experiments, and
      for the last 23 years it has played a pivotal role in the oversight of human gene
      therapy. The RAC's existence obviated the need for more restrictive governmental
      legislation and has supported the development of genetic interventions that are
      leading to actual human therapies.

PMID- 24444186
TI  - Aluminium adjuvants and adverse events in sub-cutaneous allergy immunotherapy.
AB  - Sub-cutaneous immunotherapy is an effective treatment for allergy. It works by
      helping to modify or re-balance an individual's immune response to allergens and
      its efficacy is greatly improved by the use of adjuvants, most commonly,
      aluminium hydroxide. Aluminium salts have been used in allergy therapy for many
      decades and are assumed to be safe with few established side-effects. This
      assumption belies their potency as adjuvants and their potential for biological
      reactivity both at injection sites and elsewhere in the body. There are very few
      data purporting to the safety of aluminium adjuvants in allergy immunotherapy and
      particularly so in relation to longer term health effects. There are, if only
      few, published reports of adverse events following allergy immunotherapy and
      aluminium adjuvants are the prime suspects in the majority of such incidents.
      Aluminium adjuvants are clearly capable of initiating unwanted side effects in
      recipients of immunotherapy and while there is as yet no evidence that such are
      commonplace it is complacent to consider aluminium salts as harmless constituents
      of allergy therapies. Future research should establish the safety of the use of
      aluminium adjuvants in sub-cutaneous allergy immunotherapy. 

PMID- 24444185
TI  - Influence of resource levels, organic compounds and laboratory colonization on
      interspecific competition between the Asian tiger mosquito Aedes albopictus
      (Stegomyia albopicta) and the southern house mosquito Culex quinquefasciatus.
AB  - The mosquitoes Aedes albopictus (Stegomyia albopicta) (Skuse) and Culex
      quinquefasciatus (Say) (Diptera: Culicidae) are common inhabitants of tyres and
      other artificial containers, which constitute important peridomestic mosquito
      breeding habitats. We tested the hypotheses that interspecific resource
      competition between the larvae of these species is asymmetrical, that the
      concentration of chemicals associated with decomposing detritus affects the
      competitive outcomes of these species, and that wild and colonized strains of Cx.
      quinquefasciatus are affected differently by competition with Ae. albopictus. We
      conducted two laboratory competition experiments wherein we measured survivorship
      and estimated population growth (lambda') in both species under multiple mixed
      species densities. Under varying resource levels, competition was asymmetrical:
      Ae. albopictus caused competitive reductions or exclusions of Cx.
      quinquefasciatus under conditions of limited resources. In a second experiment,
      which used both wild and colonized strains of Cx. quinquefasciatus, organic
      chemical compounds associated with decomposing detritus did not affect the
      competitive outcome. The colonized strain of Cx. quinquefasciatus had greater
      survivorship and adult mass, and faster development times than the wild strain,
      but both strains were similarly affected by competition with Ae. albopictus.
      Competition between these species may have important consequences for vector
      population dynamics, especially in areas in which tyres and artificial containers
      constitute the majority of mosquito breeding habitats. 

PMID- 24444188
TI  - Interpretation of electron delocalization in benzene, cyclobutadiene, and
      borazine based on visualization of individual molecular orbital contributions to
      the induced magnetic field.
AB  - The magnetic response of the valence molecular orbitals (MOs) of benzene,
      cyclobutadiene, and borazine to an external magnetic field has been visualized by
      calculating the chemical shielding in two-dimensional grids of points on the
      molecular plane and on a plane perpendicular to it, using gauge-including atomic
      orbitals (GIAOs). The visualizations of canonical MO contributions to the induced
      magnetic field (CMO-IMF) provide a clear view of the spatial extension, the
      shape, and the magnitude of shielding and deshielding areas within the vicinity
      of the molecule, originating from the induced currents of each valence orbital.
      The results are used to investigate the delocalization of each valence MO and to
      evaluate its contribution to the aromatic character of systems under study. The
      differentiation of the total magnetic response among the three molecules
      originates exclusively from pi-HOMO orbitals because the magnetic response of the
      subsets of the remaining MOs is found to be almost identical. Borazine is
      classified as nonaromatic as the four electrons that occupy the pi-HOMO are found
      to be strongly localized on nitrogen centers. CMO-IMF can clarify the
      interpretation of various NICS indexes and can be applied for the investigation
      of various types of electron delocalization. 

PMID- 24444187
TI  - Analysis of factors predicting mortality of new patients commencing renal
      replacement therapy 10 years of follow-up.
AB  - BACKGROUND: The natural history of patients commencing dialysis in East Yorkshire
      is not well characterised and there is little convincing evidence which has
      studied the impact of potential factors prior to commencement of renal
      replacement therapy (RRT) at predicting mortality during dialysis. The aim of
      this study was to examine the previously published 5-year data on end stage renal
      disease and co-morbid risk factors for mortality at 10 years. METHODS: An
      observational cohort study of subjects commencing dialysis in 2001/02 in East
      Yorkshire with a mean follow up from dialysis initiation of 8.8 years. Predictors
      of mortality were determined by univariate, multivariate analysis and survival
      via Kaplan-Meier analysis. Assessment of the utility of the Tangri risk
      calculator was carried out in addition to slope change in eGFR prior to dialysis
      commencement. RESULTS: Baseline characteristics and the preferred mode of
      dialysis remained concordant with the original trial. The mortality rate at the
      end of the study period was 60% (56/94) with 30% (29) of patients having been
      transplanted. Highlighted in the 5 year data a significant proportion of
      mortality was made up of vascular disease and sepsis (71%) but this proportion
      had decreased (57%) by 10 years. Cardiac disease was the commonest cause of death
      but notably in 18% of patients, death was related to dialysis or withdrawal of
      treatment. Vascular disease and diabetes remained independent risk factors and
      predicative of mortality. Calcium-phosphate product which was associated in the
      early years with mortality was not in later years. Use of the risk calculator was
      predictive of commencement of RRT but not mortality but slope change in eGFR was
      predictive of mortality. CONCLUSIONS: Although diabetes and vascular disease
      remained predictive of mortality, interestingly calcium-phosphate levels are no
      longer significant and may be a more specific predictor of early cardiac
      mortality. Slope eGFR changes prior to RRT are a predictor of mortality. We
      speculate that aggressive management of cardiac risk factors in addition to early
      transplantation may be key to influencing the impact of survival in this cohort
      in addition to possible measures to delay renal progression.

PMID- 24444189
TI  - Rectus sheath hematoma due to cough in an elderly patient under antiplatelet
      therapy.
AB  - BACKGROUND AND AIMS: Abdominal rectus sheath hematoma (ARSH) is a rare clinical
      condition that can be confused with other causes of acute abdomen. METHODS: We
      report an 83-year-old woman receiving antiplatelet medication who presented with
      ARSH following a cough episode. RESULTS: The patient was hospitalized with a
      diagnosis of acute chronic obstructive pulmonary disease exacerbations. During
      hospital stay, sudden onset abdominal pain was developed following a severe cough
      episode. Computed tomography of the abdomen revealed ARSH. DISCUSSION: Rectus
      sheath hematoma is a rare and often misdiagnosed clinical condition. It is
      important to be considered for the diagnosis. CONCLUSION: ARSH should be
      considered in case of development of acute abdominal pain following cough in
      receiving anticoagulant or antiplatelet therapy.

PMID- 24444190
TI  - Equipment-free quantitative measurement for microfluidic paper-based analytical
      devices fabricated using the principles of movable-type printing.
AB  - Microfluidic paper-based analytical devices (MUPADs) are a growing class of low
      cost chemo/biosensing technologies designed for point-of-use applications. In
      this article, we describe MTWP (movable-type wax printing), a facile method for
      the fabrication of MUPADs. MTWP is inspired by the Chinese movable-type printing
      and requires only a hot plate and homemade small iron movable components. It is
      able to pattern various wax microstructures in paper via a simple adjustment of
      the number, patterning forms or types of the metal movable components. This
      inexpensive and versatile method may thus hold great potential for producing wax
      patterned MUPADs by untrained operators at minimized cost in developing
      countries. In addition, two novel equipment-free assay methods are further
      developed to render MUPAD measurements straightforward and quantitative. They use
      the flow-through time of a detection reagent in a three-dimensional paper device
      and the number of colored detection microzones in a 24-zone paper device as the
      detection motifs. The timing method is based on the selective wettability change
      of paper from hydrophilic to hydrophobic that is mediated by enzymatic reactions.
      The counting method is carried out on the basis of oxidation-reduction reactions
      of a colored substance, namely iodine. Their utility is demonstrated with
      quantitative detection of hydrogen peroxide as a model analyte. These methods
      require only a timer or a cell phone with a timing function and the abilities of
      seeing color and of counting for quantitative MUPAD measurement, thus making them
      simple, cost-efficient, and useful sensor technologies for a great diversity of
      point-of-need applications especially in resource-poor settings. 

PMID- 24444191
TI  - Pyrosequencing for assessing diversity of eukaryotic microbes: analysis of data
      on marine planktonic ciliates and comparison with traditional methods.
AB  - Assessing microbial diversity requires analysis of all three domains of life,
      including eukaryotic microbes. We examined the diversity of two ecologically
      important clades of microbial eukaryotes, ciliates in the subclasses Oligotrichia
      and Choreotrichia (class Spirotrichea), by comparing pyrosequencing to Sanger
      sequenced clone libraries and microscopy. Using samples from a large temperate
      estuary (Long Island Sound, USA), we gained three major insights. First, richness
      estimates varied by up to one order of magnitude either using different criteria
      for pyrosequence processing or among pyrosequencing, cloning and microscopy,
      while taxon identification was almost always coherent. Error-correcting
      algorithms for pyrosequences ('denoising') reduced discrepancies in richness but
      also removed known morphospecies from the data. Second, although most of the
      pyrosequenced operational taxonomic units (OTUs) were distributed within known
      orders and families, we found evidence of a previously uncharacterized or unknown
      clade even in these ciliate lineages that have a rich history of morphological
      description. Third, pyrosequencing allowed the detection of OTUs that were either
      dominant or extremely rare in different samples. Our findings confirm the
      potential of pyrosequencing for quantifying microbial diversity, but also
      highlight the importance of careful evaluation of pyrosequence processing for
      using this method to address ecological questions. 

PMID- 24444193
TI  - Four weeks of training with different aerobic workload distributions--effect on
      aerobic performance.
AB  - Although numerous authors have studied the effect of different training
      procedures on athlete's resistance performance, there are no studies on how the
      improvement of aerobic resistance is affected by the distribution of training
      loads. This research sets out to analyse the effectiveness on aerobic activity of
      distributions with a constant load (CON) and with increments in intensity (INC)
      over a 4-week period. A total of 30 athletes took part in the analysis (38.7 +/-
      9.8 years; 174.7 +/- 6.5 cm; 72.0 +/- 9.8 kg). They were divided into 3 groups of
      10 each. One group followed a training plan with a CON distribution and another
      with an INC distribution. Both groups performed at the same volume and intensity,
      the only difference between them being the distribution of load over the 4 weeks.
      The third group trained with a free load distribution during this time.
      Improvement in VO2max and ventilatory thresholds (VT1 and VT2) was analysed
      before and after the 4-week training period. There was no modification of the
      VO2max in any of the training programmes. The FRE and INC groups showed a
      significant decrease (p<0.05) in their VO2 in VT1, and in the CON group there was
      a significant reduction (p<0.05) in heart rate in VT2. These results show how
      training periodisation produces different improvement on performance and
      demonstrate the effectiveness of periodisated programmes, because periodisated
      programmes obtain equal or higher adaptations with lower training volumes than
      non-periodisated programmes.

PMID- 24444192
TI  - Prosthetic heart valves in pregnancy: a systematic review and meta-analysis
      protocol.
AB  - BACKGROUND: Advances in surgical technique, prosthetic heart valve design, and
      anticoagulation have contributed to an overall improvement in morbidity and
      mortality in women with heart valve prostheses as well as increased feasibility
      of pregnancy. Previous work investigating the pregnancies of women with
      prosthetic valves has been directed largely toward understanding the influence of
      anticoagulation regimen. There has been little investigation on maternal and
      infant outcomes. The objective of this systematic review will be to assess the
      outcomes of pregnancy in women with heart valve prostheses in contemporary
      populations. METHODS/DESIGN: A systematic search of Medline, Embase, Cumulative
      Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library
      will be undertaken. Article titles and abstracts will be evaluated by two
      reviewers for potential relevance. Studies that include pregnancies occurring
      from 1995 onwards and where there are six or more pregnancies in women with heart
      valve prostheses included in the study population will be reviewed for potential
      inclusion. Primary outcomes of interest will be mortality (maternal and
      perinatal). Secondary outcomes will include other pregnancy outcomes. No language
      restrictions will be applied. Methodological quality and heterogeneity of studies
      will be assessed. Data extraction from identified articles will be undertaken by
      two independent reviewers using a uniform template. Meta-analyses will be
      performed to ascertain risk of adverse events and, where numbers are sufficient,
      by type of prosthesis and location as well as other subgroup analyses.
      DISCUSSION: Estimates of the risk of adverse events in recent pregnancies of
      women with heart valve prosthesis will provide better information for counselling
      and decision making. Given the improvements in prognosis of heart valve
      prosthesis recipients and the paucity of definitive data regarding optimal
      pregnancy management for these women, review of this topic is pertinent. REVIEW
      REGISTRATION: This protocol has been registered with the international
      prospective register of systematic reviews (PROSPERO) as number CRD42013006187,
      accessible online at
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013006187#.Utk7qNJ9
      f8.

PMID- 24444194
TI  - Cyclists and triathletes have different body positions on the bicycle.
AB  - Our study evaluated differences in body position on the bicycle for recreational
      cyclists, competitive cyclists and triathletes. Thirty-six recreational cyclists,
      17 competitive road cyclists and 18 competitive triathletes were assessed for
      body position on their bicycles on a cycle trainer. Images were taken of
      cyclists/triathletes in static poses with the crank at the 3 o'clock and 6
      o'clock positions. Trunk, pelvis, hip, knee and ankle angles, anterior-posterior
      and medio-lateral positions of the knees in relation to the pedal axis and
      frontal projected area were measured using ImageJ. Comparison of body position
      between groups (recreational, competitive road cyclists and competitive
      triathletes) was conducted using effects sizes (ES). The greatest differences
      between groups in the measured variables were observed between the triathletes
      and the other two groups. Smaller differences were observed between competitive
      and recreational cyclists. Competitive triathletes had greater body forward
      projection (10% greater trunk flexion and 66% knee anterior position, ES = 2.5
      and 1.2, respectively) and less frontal projected area (17%, ES = 1.3) than
      competitive road cyclists for body position on the bicycle. Both recreational and
      competitive cyclists sat on their bicycles with their trunks in a more vertical
      position compared to triathletes. Guidelines for bicycle configuration for
      triathletes and road cyclists need to consider the body positions during events.

PMID- 24444195
TI  - The effects of air travel on performance measures of elite Australian rugby
      league players.
AB  - The current study explored the effects of short haul air travel within the same
      country on elite Australian rugby league (RL) players (n=12) during two away and
      two home games of elite competition. Physiological tests of handgrip strength and
      leg power were assessed along with psychological tests and perceptions of leg
      soreness and tiredness on the day before the game (Time 1 and Time 2) and on game
      day (Time 3). Game statistics of tackles and metres gained were assessed for the
      games analysed. Significant differences were found for daily analyses of life
      demands for athletes (DALDA) worse than normal responses at Time 2 (2.50 +/- 3.23
      vs. 3.50 +/- 3.93; P=0.04), Karolinska Sleepiness Scale (KSS) at Time 2 (2.88 +/-
      1.51 vs. 3.71 +/- 1.37; P=0.011) and leg tiredness at Time 3 (3.38 +/- 1.66 vs.
      2.35 +/- 1.70; P=0.004) between home and away games. The analysis of game
      statistics identified that more metres were gained during home games (83.6 +/-
      49.1 vs. 63.0 +/- 30.1; P=0.02) and more tackles made while playing away (18.4 +/
      9.2 vs. 14.3 +/- 6.7; P=0.016). The results suggest that short haul air travel
      without crossing time zones results in symptoms of travel fatigue but does not
      appear to negatively impact on elite RL players ability to perform strength and
      power tasks. Different game tactics (attacking vs. defensive) occurred between
      home and away games however, it is unclear whether travel fatigue or a home
      advantage (HA) is associated with this finding.

PMID- 24444196
TI  - Athletes' precompetitive sleep behaviour and its relationship with subsequent
      precompetitive mood and performance.
AB  - This investigation examined precompetitive sleep behaviour of 103 athletes and
      how it relates to precompetitive mood and subsequent performance. Results
      revealed that on the night before competition athletes slept well under the
      recommended target of eight hours of sleep for healthy adults, with almost 70% of
      athletes experiencing poorer sleep than usual. It was found that anxiety, noise,
      the need to use the bathroom and early event times were amongst the most commonly
      reported causes of disrupted sleep in athletes on the night prior to competition.
      The negative moods of fatigue and tension were both significantly negatively
      correlated with precompetitive relative sleep quality (r = -0.28, P = 0.004, r = 
      0.21, P = 0.030, respectively) and total sleep time (r = -0.23, P = 0.023, r = 
      0.20, P = 0.044, respectively). Additionally, tension was positively correlated
      with number of awakenings (r = -0.20, P = 0.045). Vigour was seen to be
      significantly positively associated with relative sleep quality (r = 0.24,
      P=0.013). The relationships between relative sleep quality and fatigue, tension
      and vigour accounted for approximately 4 - 5% of the variance in mood scores.
      Disrupted sleep did not demonstrate any significant relationship with relative
      sporting performance. Conclusions from the present investigation are that
      athletes may be at particular risk of disrupted sleep on the night prior to
      competition, and this disruption can negatively relate to an athlete's
      precompetitive mood states.

PMID- 24444197
TI  - Heat acclimation responses of an ultra-endurance running group preparing for hot
      desert-based competition.
AB  - Heat acclimation induces adaptations that improve exercise tolerance in hot
      conditions. Here we report novel findings into the effects of ultra-marathon
      specific exercise load in increasing hot ambient conditions on indices of heat
      acclimation. Six male ultra-endurance runners completed a standard pre
      acclimation protocol at 20 degrees C ambient temperature (T amb), followed by a
      heat acclimation protocol consisting of six 2 h running exercise-heat exposures
      (EH) at 60% VO2max on a motorised treadmill in an environmental chamber. Three EH
      were performed at 30 degrees C T amb, followed by another three EH at 35 degrees
      C T amb. EH were separated by 48 h within T amb and 72 h between T amb. Nude body
      mass (NBM), blood and urine samples were collected pre-exercise; while NBM and
      urine were collected post-exercise. Rectal temperature (T re), heart rate (HR),
      thermal comfort rating (TCR) and rating of perceived exertion were measured pre
      exercise and monitored every 5 min during exercise. Water was provided ad libitum
      during exercise. Data were analysed using a repeated measures and one-way
      analysis of variance (ANOVA), with post hoc Tukey's HSD. Significance was
      accepted as P< 0.05. Overall mean T re was significantly lower during 30 degrees
      C EH3 and 35 degrees C EH3 compared with their respective EH1 (-0.20 and-0.23
      degrees C, respectively; P<0.05). Similarly, overall mean HR was significantly
      lower during 30 degrees C EH3 and 35 degrees C EH3 compared with their respective
      EH1 (8 and 7 bpm respectively; P<0.05). A significant decrease in overall mean
      TCR was observed during 35 degrees C EH3, compared with 35 degrees C EH1 (P<
      0.05). Significant increases in resting pre-exercise plasma volume (estimated
      from Hb and Hct) were observed by 30 degrees C EH3 (7.9%; P< 0.05). Thereafter,
      plasma volume remained above baseline throughout the experimental protocol. Two
      EH of 2 h at 60% VO2max at 30 degrees C T amb was sufficient to initiate heat
      acclimation in all ultra-endurance runners. Further, heat acclimation responses
      occurred with increasing EH to 35 degrees C T amb. Preventing exertional heat
      illnesses and optimising performance outcomes in ultra-endurance runners may
      occur with exposure to at least 2 h of exercise-heat stress on at least two
      occasions in the days leading up to multi-stage ultra-marathon competition in the
      heat.

PMID- 24444198
TI  - Aerobic exercise does not change C-reactive protein levels in non-obese patients
      with obstructive sleep apnoea.
AB  - The aim of this study is to evaluate the effects of a 2-month aerobic exercise
      training programme on C-reactive protein (CRP) levels in non-obese patients with
      obstructive sleep apnoea. Twenty non-obese and sedentary adult male volunteers
      underwent polysomnography (PSG) to assess their sleep parameters. After the PSG
      analysis, the subjects were divided into two groups (CTRL, control and OSA,
      obstructive sleep apnoea). Twenty-four sessions of aerobic exercise were
      performed, and PSG was repeated on the night that followed the last physical
      training session (24th). Blood samples were collected for CRP analysis before the
      first exercise session and after the last session. The OSA group demonstrated a
      reduction in sleep latency (SL) after 2 months of physical exercise, and 80% of
      them showed a lower apnoea-hypopnoea index (AHI), although this difference was
      not statistically significant. The differences between the CRP values for the
      CTRL and OSA groups were also not statistically significant at baseline or after
      2 months of physical exercise. Furthermore, there was no correlation between the
      CRP levels and body mass index (BMI) in the two groups assessed. Our results
      suggest that in non-obese patients with OSA, CRP levels were normal and did not
      change after 2 months of aerobic exercise training.

PMID- 24444199
TI  - Physical match performance of youth football players in relation to physical
      capacity.
AB  - The aims of the study were to (1) analyse the activity profile of youth football
      players during competitive matches, and (2) examine the relationship between
      physical match performance and intermittent exercise performance as well as
      VO2max. Thirty youth male football players, aged 14-17 years, carried out a
      laboratory treadmill test for determination of VO2max as well as the Yo-Yo
      intermittent recovery level 1 (Yo-Yo IR1) and Yo-Yo intermittent endurance level
      2 (Yo-Yo IE2) tests. Time-motion analysis and heart rate (HR) recordings were
      performed during two competitive matches per player. Distance covered during the
      match was 6311 +/- 948 (range: 4435-8098) m, of which 12% were high-intensity
      activities (HIA; 759 +/- 437 [374-2062] m), and 5% was backwards running (309+/
      205 [12-776] m). Mean match HR was 168 +/- 12 (140-187) bpm, corresponding to 85%
      (69-91) of maximum HR. The total distance covered in the last 13.3-min period of
      the match was 40%, 26% and 17% lower than in the first, second and fourth 13.3
      min periods of the match, respectively (P<0.05). The distance covered in
      backwards running decreased by 31% and 37% from the first to the last 13.3-min
      periods of the first and second half, respectively (P<0.05). The Yo-Yo IR1 was
      significantly associated with the time spent with sprinting during the match
      (r=0.63; P=0.002) and during the last 13.3-min period (r=0.63; P=0.022). Both Yo
      Yo IR1 and Yo-Yo IE2 were correlated with the time spent with match HIA (r=0.56
      and r=0.57, respectively; P<0.05). No significant relationship was observed
      between VO2max and match time-motion variables (r=-0.13-0.25; P>0.05) or Yo-Yo
      test performances (r=0.09-0.26; P>0.05). In conclusion, youth football players
      have a high heart-rate loading during match play and a decreased running
      performance towards the end of the game. The intermittent exercise capacity, as
      determined in the Yo-Yo IR1 test, appears to be a valid indicator of high
      intensity exercise performance in youth matches.

PMID- 24444200
TI  - Fasting improves static apnea performance in elite divers without enhanced risk
      of syncope.
AB  - In competitive apnea divers, the nutritional demands may be essentially different
      from those of, for example, endurance athletes, where energy resources need to be
      maximised for successful performance. In competitive apnea, the goal is instead
      to limit metabolism, as the length of the sustainable apneic period will depend
      to a great extent on minimising oxygen consumption. Many but not all elite divers
      fast before performing static apnea in competition. This may increase oxygen
      consumption as mainly lipid stores are metabolised but could also have beneficial
      effects on apneic duration. Our aim was to determine the effect of over-night
      fasting on apnea performance. Six female and seven male divers performed a series
      of three apneas after eating and fasting, respectively. The series consisted of
      two 2-min apneas spaced by 3 min rest and, after 5 min rest, one maximal effort
      apnea. Apneas were performed at supine rest and preceded by normal respiration
      and maximal inspiration. Mean (+/- SD) time since eating was 13 h (+/- 2 h 43
      min) for the fasting and 1 h 34 min (+/- 33 min) for the eating condition (P <
      0.001). Mean blood glucose was 5.1 (+/- 0.4) mmol/L after fasting and 5.9 (+/-
      0.7) mmol/L after eating (P<0.01). Lung volumes were similar in both conditions
      (NS). For the 2-min apneas, nadir SaO2 during fasting was 95 (+/- 1)% and 92 (+/-
      2)% (P < 0.001) on eating and ETCO2 was lower in the fasting condition (P < 0.01)
      while heart rate (HR) during apnea was 74 (+/- 10) bpm for fasting and 80 (+/-
      10) bpm for eating conditions (P < 0.01). Maximal apnea durations were 4 min 41 s
      (+/- 43 s) during fasting and 3 min 51 s (+/- 37 s) after eating (P < 0.001), and
      time without respiratory contractions was 31 s (25%) longer after fasting (P <
      0.01). At maximal apnea termination, SaO2 and ETCO2 were similar in both
      conditions (NS) and apneic HR was 63 (+/- 9) bpm for fasting and 70 (+/- 10) bpm
      for eating (P < 0.01). The 22% longer apnea duration after fasting with analogous
      end apnea SaO2 levels suggests that fasting is beneficial for static apnea
      performance in elite divers, likely via metabolism-limiting mechanisms. The
      oxygen-conserving effect of the more pronounced diving response and possibly
      other metabolism-limiting mechanisms related to fasting apparently outweigh the
      enhanced oxygen consumption caused by lipid metabolism.

PMID- 24444201
TI  - Investigating reaction times and stopping performance of skiers and snowboarders.
AB  - On-slope experiments were performed to determine the reaction time of
      recreational skiers and snowboarders. Volunteers riding a slope were instructed
      to brake to a complete stop after a visual and acoustic signal. Reaction time and
      parameters such as the duration of the braking manoeuvre and the corresponding
      stopping distance were recorded. A total of 70 runs were evaluated, including 37
      runs with snowboarders and 33 runs with skiers. The average time until the first
      observable reaction (reaction time) for all athletes was 420 ms; there was no
      statistically significant difference between skiers and snowboarders.
      Participants needed on average an additional 470 ms until they actually started
      braking. Snowboarders needed significantly more time to prepare for braking than
      skiers and it took snowboarders significantly longer to stop (p<0.05). In line
      with these findings, snowboarders also exhibited significantly less deceleration
      during braking compared to skiers. This study quantifies the reaction times of
      skiers and snowboarders and provides data related to braking of skiers and
      snowboarders. This data is useful for the development of injury prevention
      measures and can be used to ensure reasonable slope design.

PMID- 24444202
TI  - Anthropometric variables and their relationship to performance and ability in
      male surfers.
AB  - Abstract The aim of this study was to evaluate the anthropometric profiles of
      male surfers and to investigate the relationship of these measures with
      performance and ability. Following institutional ethical approval, 79 male
      surfers underwent anthropometric assessment. These surfers composed of three sub
      groups of professional (n=17; age: 34.12, s =3.81 years, stature: 177.28, s =6.29
      cm; body mass: 78.57, s =7.17 kg), junior national level (n=15; age: 15.61, s
      =1.06 years, stature: 173.86, s =5.72 cm; body mass: 63.27, s =7.17 kg) and
      intermediate level surfers (n=47; age: 22.47, s =2.80 years, stature: 179.90, s
      =5.41; body mass: 77.83, s =9.43 kg). The mean somatotype values for the
      different groups of surfers were found to be 2.48, 5.00 and 1.03 for the
      professional surfers; 2.18, 3.72 and 3.24 for the junior national surfers and
      2.79, 3.57 and 2.42 for the intermediate surfers. Professional surfers were
      significantly (P < 0.01) more mesomorphic and less ectomorphic than intermediate
      level surfers. Significant correlations were observed between endomorphy (r = 
      0.399, P < 0.01), sum of six skinfolds (r = -0.341, P < 0.05), and body fat
      percentage (r = -0.380, P < 0.01) and the rating of ability among the
      intermediate group of surfers. Across all participants, the rating of surfer
      ability was significantly correlated with endomorphy (r = -0.366, P <= 0.01),
      mesomorphy (r = 0.442, P < 0.01), sum of six skinfolds (r = -0.274, P < 0.05) and
      body fat percentage (r = -0.268, P < 0.05). Findings suggest that the levels of
      adiposity and muscularity may influence the potential for progression between
      intermediate and professional-level surfing performance.

PMID- 24444203
TI  - From early to adult sport success: analysing athletes' progression in national
      squads.
AB  - Although some prospective studies have shown that many successful young athletes
      do not maintain the same level of success when they reach adulthood, there is
      still a lack of information regarding athletes who started their international
      involvement at early ages. Therefore, the purpose of the present study was to
      investigate the international pathway of male and female athletes in different
      sports from the moment of their competitive debut, in order to determine how many
      international athletes at early ages competed or did not compete internationally
      as juniors and/or seniors. The sample included 395 athletes (soccer, volleyball,
      swimming and judo), born between 1974 and 1981, who could have competed in their
      national squads between 1988 and 2008. Results showed that only a third of
      international pre-junior athletes reappeared as senior athletes, confirming the
      difficulties of predicting late success based on early identification and
      selection.

PMID- 24444204
TI  - Interrelationships between different loads in resisted sprints, half-squat 1 RM
      and kinematic variables in trained athletes.
AB  - Resisted sprint running is a common training method for improving sprint-specific
      strength. It is well-known that an athlete's time to complete a sled-towing
      sprint increases linearly with increasing sled load. However, to our knowledge,
      the relationship between the maximum load in sled-towing sprint and the sprint
      time is unknown, The main purpose of this research was to analyze the
      relationship between the maximum load in sled-towing sprint, half-squat maximal
      dynamic strength and the velocity in the acceleration phase in 20-m sprint. A
      second aim was to compare sprint performance when athletes ran under different
      conditions: un-resisted and towing sleds. Twenty-one participants (17.86 +/- 2.27
      years; 1.77 +/- 0.06 m and 69.24 +/- 7.20 kg) completed a one repetition maximum
      test (1 RM) from a half-squat position (159.68 +/- 22.61 kg) and a series of sled
      towing sprints with loads of 0, 5, 10, 15, 20, 25, 30% body mass (Bm) and the
      maximum resisted sprint load. No significant correlation (P<0.05) was found
      between half-squat 1 RM and the sprint time in different loaded conditions.
      Conversely, significant correlations (P<0.05) were found between maximum load in
      resisted sprint and sprint time (20-m sprint time, r=-0.71; 5% Bm, r=-0.73; 10%
      Bm, r=-0.53; 15% Bm, r=-0.55; 20% Bm, r=-0.65; 25% Bm, r=-0.44; 30% Bm, r=-0.63;
      MaxLoad, r= 0.93). The sprinting velocity significantly decreased by 4-22% with
      all load increases. Stride length (SL) also decreased (17%) significantly across
      all resisted conditions. In addition, there were significant differences in
      stride frequency (SF) with loads over 15% Bm. It could be concluded that the
      knowledge of the individual maximal load in resisted sprint and the effects on
      the sprinting kinematic with different loads, could be interesting to determinate
      the optimal load to improve the acceleration phase at sprint running.

PMID- 24444205
TI  - Variations in relative age effects in individual sports: skiing, figure skating
      and gymnastics.
AB  - In many sports, policy-makers and administrators employ annual cohorts to reduce
      differences between athletes during childhood and youth. Although well-intended,
      unintended relative age effects (RAEs) usually occur. RAEs refer to the specific
      selection, participation and attainment disadvantages associated with
      participants' birthdates relative to an arbitrary 'cutoff' date used to group
      participants within annual age groups. To date, we have little understanding of
      RAEs in individual sports. In this article, Study 1 considered the presence of
      RAEs in 1474 ski jumping, 7501 cross-country skiing, 15,565 alpine skiing, 4179
      snowboarders and 713 Nordic combined athletes. Chi-square analyses revealed
      significant RAEs for most of these contexts across sexes. In Study 2, RAEs in the
      aesthetic sports of figure skating (n=502) and female gymnastics (n=612) were
      considered. There was no effect for the figure skaters and an atypical effect for
      the gymnasts. The significant effects across most ski sports coupled with the
      null effects in figure skating and atypical effect in gymnastics suggest that
      sport-specific contextual factors are important elements in understanding the
      mechanisms of RAEs, although further work is necessary to validate these
      findings.

PMID- 24444206
TI  - Predicting the names of the best teams after the knock-out phase of a cricket
      series.
AB  - Cricket players' performances can best be judged after a large number of matches
      had been played. For test or one-day international (ODI) players, career data are
      normally used to calculate performance measures. These are normally good
      indicators of future performances, although various factors influence the
      performance of a player in a specific match. It is often necessary to judge
      players' performances based on a small number of scores, e.g. to identify the
      best players after a short series of matches. The challenge then is to use the
      best available criteria in order to assess performances as accurately and fairly
      as possible. In the present study the results of the knock-out phase of an
      International Cricket Council (ICC) World Cup ODI Series are used to predict the
      names of the best teams by means of a suitably formulated logistic regression
      model. Despite using very sparse data, the methods used are reasonably
      successful. It is also shown that if the same technique is applied to career
      ratings, very good results are obtained.

PMID- 24444207
TI  - The influence of range of motion versus application of force on vertical jump
      performance in prepubescent girls and adult females.
AB  - This study examined whether during childhood, the parameters for the range of
      motion had more influence on vertical jump height than parameters for application
      of force. Counter-movement jumps performed by 36 girls aged between 5 and 8 years
      and 20 adult females were examined using force platform analysis. Multiple
      regression analysis of the data indicated that the parameters for the range of
      motion had more influence on jump height than the parameters for application of
      force. This was demonstrated by standardised coefficients for range of motion
      which were higher than the standardised coefficients for application of force.
      Although this trend was observed in both groups, the influence of the range of
      motion was relatively greater in prepubescent girls than in adult females. The
      present results suggest that prepubescent girls increased their jump height by
      increasing the range of motion over which force is applied.

PMID- 24444208
TI  - Sleep quality under mild hypoxia in men with low hypoxic ventilatory response.
AB  - The present study evaluated whether slow-wave sleep and whole-night delta power
      of the non-rapid eye movement (NREM) sleep electroencephalogram (EEG) decrease
      during sleep at a simulated altitude of 2000 m, and whether such changes related
      to measures of hypoxic ventilatory response (HVR). This study consisted of two
      parts; in the first, HVR was measured in 41 subjects and each seven subjects with
      the lowest or the highest HVR were selected for the subsequent sleep study. In
      the second part, polysomnogram, arterial oxygen saturation (SpO2) and respiratory
      events are recorded on the selected subjects under normoxic and hypoxic
      conditions. Hypoxia decreased SpO2 and increased respiratory disturbances for
      both groups. The low HVR group, but not the high HVR group, showed decreases in
      the whole-night delta power of NREM sleep EEG under hypoxia. On the other hand,
      two subjects in the high HVR group, who showed relatively high apnoea indices,
      also showed lower SpO2 nadirs and decreases in the whole-night delta power under
      hypoxia. These results suggest that acute hypoxia equivalent to that at a 2000 m
      altitude decreases slow-wave sleep in individuals that show low HVR. However, low
      HVR may not be the only, but one of some factors that decrease the whole-night
      delta power under hypoxia. Therefore, it was not sufficient to identify
      individuals likely to be susceptible to deteriorated sleep quality at a simulated
      altitude of 2000 m only using the HVR test. Other factors, which relate to
      respiratory instabilities, should be taken into consideration to identify them.

PMID- 24444209
TI  - Relative age-related participation and dropout trends in German youth sports
      clubs.
AB  - Relative age describes a youth's age within their age group cohort. Compared to
      relatively younger peers, relatively older youth in an annual age group cohort
      have been found more likely to be selected to sports teams, and to receive higher
      grades in education. This study examined the influence of youth sport
      participants' relative age on participation and dropout. Using data from the 1995
      German Youth Sport Survey (N total=2612), comparisons (stratified by gender and
      sport type) were made between the relative age of current and former
      participants. Analyses also considered the type of school youths were enrolled in
      while exploring the influence of relative age on sport participations. No
      relative age effects for dropout emerged among males in team or individual sport
      contexts. Female dropouts were more likely to be relatively older (Q1, OR
      adjusted: 0.52, 95% CI: 0.34-0.80; Q2, OR adjusted: 0.55, 95% CI: 0.36-0.84; Q3,
      OR adjusted: 0.59, 95% CI: 0.39-0.89), an effect that was mirrored among
      'artistic' sport participants. Boys and girls in schools that were for children
      of higher academic proficiency were more likely to be currently participating in
      sport. Findings suggest that relative age-related dropout effects may be context
      sensitive and different for males and females. For the most part, relative age
      did not appear to have any relationship with dropout in this sample, with some
      notable exceptions for females. Overall, factors such as the type of school
      youths were enrolled in appear to be a more salient influence on sport
      participation than relative age.

PMID- 24444210
TI  - Foul or dive? Motor contributions to judging ambiguous foul situations in
      football.
AB  - Football (soccer) referees frequently face situations in which they have to
      distinguish dives and fouls. Yet, little is known about the contributing factors
      that characterise the ability to judge these ambiguous situations correctly. To
      this end, in the current article we tested the hypothesis that motor experience
      of observers contributes to the visual identification of deceptive actions.
      Thereto, we asked skilled football referees, skilled football players, wheelchair
      bounded football fans (thus with limited motor experience) and novices to judge
      whether potential tackle situations in football were either fouls or dives.
      Results revealed that the referees (accuracy 72.2%, s=6.2) and players (accuracy
      72.0%, s=6.4) were better at discriminating fouls and dives than the fans
      (accuracy 61.1%, s=7.2) and the novices (accuracy 57.4%, s=7.0) (P < 0.001). The
      results seem to point to an added value of motor experience in detecting
      deceptive movements.

PMID- 24444211
TI  - Survey quality and cross-national sports research: a case study of the 2007 ISSP
      survey.
AB  - For the past 15 years there has been an increase in the number of cross-national
      surveys on sports-related issues. However, in cross-national research, the
      quality of the conclusions always depends on the quality of each of the separate
      national studies. If any of these are flawed, it is possible that the observed
      variation in outcomes is nothing more than a methodological artefact.
      Unfortunately, the issue of survey quality has been seriously underdeveloped in
      sports research literature. Through a discussion of several components of survey
      quality by means of the 2007 International Social Survey Programme survey on
      leisure time and sports, this article addresses this lacuna. Our case study shows
      that the wide cross-national variation in sampling methods, modes of data
      collection and response rates leaves room for various forms of survey error with
      the potential to generate misleading or biased findings. Although it is less
      clear what can be done about survey error, we give some possibilities. We suggest
      that ignoring these methodological problems will affect the validity of cross
      national research. Moreover, future research into the impact of various
      methodological factors related to survey quality is definitely needed.

PMID- 24444212
TI  - Quiet eye training: the acquisition, refinement and resilient performance of
      targeting skills.
AB  - How we learn and refine motor skills in the most effective manner and how we
      prevent performance breakdown in pressurised or demanding circumstances are among
      the most important questions within the sport psychology and skill acquisition
      literature. The quiet eye (QE) has emerged as a characteristic of highly skilled
      perceptual and motor performance in visually guided motor tasks. Defined as the
      final fixation that occurs prior to a critical movement, over 70 articles have
      been published in the last 15 years probing the role that the QE plays in
      underpinning skilled performance. The aim of this review is to integrate research
      findings from studies examining the QE as a measure of visuomotor control in the
      specific domain of targeting skills; motor skills requiring an object to be
      propelled to a distant target. Previous reviews have focused primarily on the
      differences in QE between highly skilled performers and their less skilled
      counterparts. The current review aims to discuss contemporary findings relating
      to 1. The benefits of QE training for the acquisition and refinement of targeting
      skills; 2. The effects of anxiety upon the QE and subsequent targeting skill
      performance and 3. The benefits of QE training in supporting resilient
      performance under elevated anxiety. Finally, potential processes through which QE
      training proffers this advantage, including improved attentional control,
      response programming and external focus, will be discussed and directions for
      future research proposed.

PMID- 24444213
TI  - Home advantage and referee bias in European football.
AB  - Home advantage is well documented in a wide range of team sports including
      association football (soccer). Home team crowd support has been shown to be a
      likely causal factor and its influence on referee decision-making appears to play
      a significant role. Match data from the 2009/2010 and 2010/2011 seasons of the
      Union of European Football Associations (UEFA) Champions League and Europa League
      were used to investigate referee bias in terms of the association between match
      location (home vs. away) and disciplinary sanctions used by football referees.
      The adjusted mean number of yellow cards received by home and away teams and the
      ratios of these means were estimated from Poisson regression models. After
      controlling for within-match measures of attacking dominance referees in the
      Champions League and Europa League issued 25% (p<0.001) and 10% (p=0.002) more
      yellow cards, respectively, to away teams than to home teams. The higher level of
      home team bias in the Champions League appeared to be mainly due to higher crowd
      densities. In a combined analysis of both UEFA leagues the magnitude of referee
      bias increased with increasing crowd density (p<0.001). Crowd size and crowd
      proximity were not associated with referee bias after controlling for crowd
      density. These results provide further evidence that crowd support influences
      referee decisions. Failure to control for within-match team performance may over
      estimate the extent of referee bias in terms of the number of disciplinary
      sanctions used.

PMID- 24444214
TI  - Acute physiological responses to recreational in-line skating in young adults.
AB  - We examined the physiological responses to in-line skating exercise at self
      selected paces in recreationally trained adults. Seven men and 10 women performed
      in-line skating exercise during which oxygen uptake (VO2) and heart rate (HR)
      were recorded continuously. Ratings of perceived exertion (RPE) and blood lactate
      concentration were also obtained at the end of exercise. Furthermore, subjects'
      peak VO2, peak HR, RPE and gas-exchange thresholds were determined in laboratory
      settings. The average exercise intensity during in-line skating was 90% of peak
      HR, 67% of peak VO2, 84% of HR reserve and 64% of VO2 reserve. When expressed as
      RPE and as metabolic equivalents (METs), the average exercise intensity was 13.1
      RPE and 9.4 METs. Overall, these indicators of exercise intensity categorise in
      line skating at self-selected paces as a vigorous physical activity. Notably, at
      similar VO2 values, significantly higher HR (174 +/- 16 vs. 156 +/- 6 bpm;
      p<0.001) and RPE (13.1 +/- 1.4 vs. 11.7 +/- 1.4; p=0.019) were observed for in
      line skating compared with treadmill running. We conclude that 1. recreational in
      line skating induces physiological responses that are sufficient for improving
      and maintaining cardiovascular fitness in healthy adults, 2. HR- and RPE-based
      methods for quantifying the exercise intensity during in-line skating may
      overestimate the actual metabolic load and 3. the derivation of exercise
      prescriptions for in-line skating should be preferably based on specific (i.e. in
      line skating) graded exhaustive exercise test.

PMID- 24444215
TI  - Top-down and bottom-up processes during observation: implications for motor
      learning.
AB  - Neurophysiological and behavioural research has linked observational practice
      (OP) to a mirroring mechanism encompassing the action-observation network (AON).
      Although, the original findings indicate that biological stimuli alone activate
      the AON, recent evidence has shown sensitivity to non-biological stimuli. Thus,
      the AON is suggested to be influenced by interacting bottom-up and top-down
      processes. In this review, we describe the multi-functional properties of the AON
      and discuss the implications for OP and subsequent motor learning.

PMID- 24444216
TI  - Objectively assessed physical activity and weight status in Maltese 11-12 year
      olds.
AB  - The objectives of the study were to identify levels of physical activity and
      sedentary time and assess how they differ by weight status in Maltese boys and
      girls. Participants were 234 Maltese children aged 11-12 years, of which 187
      (80%) provided complete data. Physical activity was assessed using accelerometry
      and weight status determined through gender-specific age-adjusted Body mass index
      (BMI). Self-reported mode of transport to school, TV and computer time, gaming
      and mobile phone use were assessed by questionnaire. Total physical activity was
      generally very low and significantly lower for girls than boys at all times on
      weekdays and on weekends till 7 pm. Overweight and obesity prevalence was 27% and
      18.6%, respectively. Differences in overall physical activity were observed
      between non-overweight, and overweight and obese boys (p=0.003). Differences in
      moderate to vigorous intensity physical activity (MVPA) in boys were significant
      across all weight categories (p=0.001) and in girls (p=0.020) between the
      overweight (27.6 min), the non-overweight (26.4 min) and the obese (18.9 min).
      For weekdays, mean physical activity differences (p=0.013) were observed between
      non-overweight (515.5 cpm) and obese boys (416.4 cpm). Differences in MVPA were
      found (p=0.038) between non-overweight (4.4 min) and obese boys in the 6 am-3 pm
      period. Differences were also found between overweight (13.2 min) and obese girls
      (8.1 min) (p=0.024) in that period. On weekends, mean physical activity
      differences were found between non-overweight and overweight boys from 8 am-7 pm
      but not for girls. Physical activity levels in this sample were very low when
      compared to recommended levels, while the prevalence of overweight and obesity
      and sedentary time were high. Girls are significantly less active than boys
      throughout the week. Activity level differences and patterning across the day and
      week were related to weight status with obese children showing markedly less
      activity. These results suggest that we need to provide more opportunities for
      overweight and obese children to be active throughout the week, with a particular
      emphasis on physical activity during school hours.

PMID- 24444217
TI  - Separate and combined influence of posture and sprint running on plasma volume
      changes.
AB  - It is currently unknown whether any changes in plasma volume (PV) after sprint
      running are inherent to sprint running per se or are due to other confounding
      factors such as changes in posture. The purpose of the present study was to
      examine the independent effects of sprint running on PV changes. Eight females
      completed two trials on separate days: (1) a 30-s sprint on a non-motorised
      treadmill and (2) a control trial where no exercise was undertaken but blood
      samples were taken at identical time points as in the exercise trial. Changes in
      PV were calculated using haematocrit and haemoglobin. Post-sprint PV reductions
      were greater in the sprint than the control trial (mean: -17.7, SD=3.1% vs. mean:
      -7.5, s = 4.9, P<0.05, n=8). There were greater changes in PV in the sprint than
      the control trial in most sampling points. These data show that sprint running of
      only 30 s induces transient reductions in PV independently of posture change. The
      present findings suggest that PV changes due to sprint running should be
      routinely reported as well as the posture and the exact time in this posture.

PMID- 24444218
TI  - Influence of exercise intensity and duration on perceived exertion in adolescent
      Taekwondo athletes.
AB  - The aim of this study was to examine the influence of exercise intensity and
      session duration on rating of perceived exertion (RPE) in adolescent Taekwondo
      (TKD) athletes. Twelve male youth competitive TKD athletes, aged between 13 and
      18 years took part in this study. Training data (368 individual sessions) were
      collected during the 12 weeks of the pre-competitive TKD season. Daily training
      load was calculated using the heart rate and the session-RPE. Exercise intensity
      was also classified in five zones [i.e. 50-60%, 61-70%, 71-80%, 81-90% and 91
      100% of maximal heart rate (HRmax)] and the time spent in each zone was expressed
      as percentage of total session time. The analysis of variance showed a
      significant main effect for zone (p<0.001) with most of the time (69%) spent at
      intensities between 61 and 90% of HRmax, and only 10% spent above 91% (mean
      differences compared to the other zones ranging from -6.6% versus zone 1 to 
      14.8% versus zone 3; p<0.0001). The individual correlation between session-RPE
      and HR-based methods were moderate to large. The stepwise multiple regression
      showed that RPE was influenced mainly by the time spent in the high intensity
      zone that explained 22.1% of the variance in RPE. Session duration accounted for
      only an additional 3.2%. The results suggest the time spent at high-intensity
      (i.e. between 91 and 100% HRmax) and only marginally the session duration
      influences the RPE referred to the whole training session. This seems to confirm
      that the determination of the TL multiplying the RPE and session duration is
      acceptable.

PMID- 24444219
TI  - The breathing effect of the LF/HF ratio in the heart rate variability
      measurements of athletes.
AB  - The purpose of this study was to measure the influence of breathing frequency
      (BF) on heart rate variability (HRV) and specifically on the Low Frequency/High
      Frequency (LF/HF) ratio in athletes. Fifteen male athletes were subjected to HRV
      measurements under six randomised breathing conditions: spontaneous breathing
      frequency (SBF) and five others at controlled breathing frequencies (CBF) (0.20;
      0.175; 0.15; 0.125 and 0.10 Hz). The subjects were divided in two groups: the
      first group included athletes with SBF <0.15 Hz (infSBF) and the second athletes
      with SBF higher than 0.15 Hz (supSBF). Fatigue and training load were evaluated
      using a validated questionnaire. There was no difference between the two groups
      for the fatigue questionnaire and training load. However, the LF/HF ratio during
      SBF was higher in infSBF than in supSBF (6.82 +/- 4.55 vs. 0.72 +/- 0.52;
      p<0.001). The SBF and LF/HF ratio were significantly correlated (R=-0.69;
      p=0.004). For the five CBF, no differences were found between groups; however,
      LF/HF ratios were very significantly different between sessions at 0.20; 0.175;
      0.15 Hz and 0.125; 0.10 Hz. In this study, BF was the main modulator of the LF/HF
      ratio in both controlled breathing and spontaneous breathing. Although, none of
      the subjects of the infSBF group were overtrained, during SBF they all presented
      LF/HF ratios higher than four commonly interpreted as an overtraining syndrome.
      During each CBF, all athletes presented spectral energy mainly concentrated
      around their BF. Consequently, spectral energy was located either in LF or in HF
      band. These results demonstrate that the LF/HF ratio is unreliable for studying
      athletes presenting SBF close to 0.15 Hz leading to misclassification in fatigue.

PMID- 24444220
TI  - Variation in the ACE, PPARGC1A and PPARA genes in Lithuanian football players.
AB  - The aim of this study was to determine the impact of ACE (I/D), PPARGC1A (G/A)
      and PPARA (G/C) polymorphisms on footballers performance among 199 Lithuanian
      professional footballers and 167 sedentary, healthy men (controls). Genotyping
      was performed using polymerase chain reaction and restriction fragment length
      polymorphism methods on DNA from leucocytes. Results revealed that the
      angiotensin-1-coverting enzyme gene (ACE) genotype distribution was significantly
      different between total football players group (II 23.6%, ID 46.7% and DD 29.6%)
      and the controls (II 24.6%, ID 29.9% and DD 45.5%; P=0.002). Although
      investigating PPARGC1A (G/A) and PPARA (G/C) polymorphisms no significant results
      were obtained in the total football players group, however, significant
      differences were determined between forwards and controls [PPARGC1A: GG 54.6%, GA
      29.5%, AA 15.9% vs. GG 49.7%, GA 44.3% and AA 6.0% (P = 0.044); PPARA: GG 52.3%,
      GC 40.9%, CC 6.8% vs. GG 72.4%, GC 24.6% and CC 3.0% (P = 0.034)]. In the whole
      cohort, the odds ratio of the genotype [ACE ID + PPARA GG] being a footballer was
      1.69 (95% CI 1.04-2.74), and of [ACE ID + PPARGC1A GG] 1.93 (95% CI 1.10-3.37)
      and of [ACE II + PPARA GC] 2.83 (95% CI 1.02-7.91) compared to controls. It was
      revealed that ACE ID genotype together with PPARA GG and PPARGC1A GG as well as
      ACE II genotype with PPARA GC is probably the 'preferable genotype' for
      footballers. Summing up, the present study suggests that the ACE, PPARGC1A and
      PPARA polymorphisms genotypes are associated, separately and in combination, with
      Lithuanian footballers' performance.

PMID- 24444221
TI  - The effects of relaxing music for anxiety control on competitive sport anxiety.
AB  - This investigation examined the effects of relaxing music for anxiety control on
      measures of competitive state anxiety and the performance of a simple motor
      skill. Seventy-two undergraduate students volunteered to participate in the
      study. Participants were informed that they would be required to partake in a
      sport competition, possibly with an audience present, and possibly whilst being
      filmed. Participants were randomly allocated to one of three intervention
      conditions, listening to relaxing music for anxiety control, listening to non
      relaxing music or a no music control. During the 10-minute intervention period,
      measures of anxiety (CSAI-2R, subjective relaxation and HR) were taken on three
      occasions (baseline, pre-intervention and post-intervention). Repeated measures
      MANOVA showed that all three interventions provoked significant reductions in
      competitive state anxiety. Condition had no impact upon any of the DVs. These
      results suggest that listening to relaxing music for anxiety control was no more
      effective at reducing competitive state anxiety than non-relaxing music or a
      period of silence. ES, mean difference and 90% CI data did however provide some
      support for the application of relaxing music for anxiety control. There were no
      between-condition differences in motor task performance.

PMID- 24444222
TI  - Gender differences in hip and ankle joint kinematics on knee abduction during
      running.
AB  - The knee is the most common site of running injuries, particularly prevalent in
      females. The purpose of this study was to clarify gender differences in the lower
      extremity kinematics during running, with a specific emphasis on the
      relationships between the distal and proximal factors and the knee joint
      kinematics. Eleven female and 11 male runners participated in this study. Three
      dimensional marker positions were recorded with a motion analysis system while
      the subjects ran along a 25 m runway at a speed of 3.5 m/s. Kinematic variables
      were analyzed for the stance phase of the right leg. Female runners demonstrated
      significantly greater peak knee abduction (P<0.05), hip adduction (P<0.01) and
      internal rotation (P<0.05), whereas male runners demonstrated significantly
      greater peak rearfoot eversion (P<0.01). The knee abduction angles were
      positively correlated with hip adduction angles (r=0.49, P<0.05) and negatively
      correlated with rearfoot eversion (r= -0.69, P<0.001). There was no significant
      difference in normalised step width between genders (P>0.05). Smaller rearfoot
      eversion and greater hip adduction related closely to the greater knee abduction
      as the distal and proximal factors, respectively. These relationships are thought
      to be the compensatory joint motions in the frontal plane, because there was no
      significant difference in the normalised step width between females and males.
      The current results suggest that if the step width is identical, the subjects
      with greater knee abduction had smaller rearfoot eversion to compensate for
      greater hip adduction, which were more apparent in females. This explains greater
      knee abduction found in female runners, which can be linked to a high risk of
      knee injury.

PMID- 24444223
TI  - Sleep or swim? Early-morning training severely restricts the amount of sleep
      obtained by elite swimmers.
AB  - Good sleep is essential for optimal performance, yet few studies have examined
      the sleep/wake behaviour of elite athletes. The aim of this study was to assess
      the impact of early-morning training on the amount of sleep obtained by world
      class swimmers. A squad of seven swimmers from the Australian Institute of Sport
      participated in this study during 14 days of high-intensity training in
      preparation for the 2008 Olympic Games. During these 14 days, participants had 12
      training days, each starting with a session at 06:00 h, and 2 rest days. For each
      day, the amount of sleep obtained by participants was determined using self
      report sleep diaries and wrist-worn activity monitors. On nights that preceded
      training days, participants went to bed at 22:05 h (s=00:52), arose at 05:48 h
      (s=00:24) and obtained 5.4 h (s=1.3) of sleep. On nights that preceded rest days,
      participants went to bed at 00:32 h (s=01:29), arose at 09:47 h (s=01:47) and
      obtained 7.1 h (s=1.2) of sleep. Mixed model analyses revealed that on nights
      prior to training days, bedtimes and get-up times were significantly earlier
      (p<0.001), time spent in bed was significantly shorter (p<0.001) and the amount
      of sleep obtained was significantly less (p<0.001), than on nights prior to rest
      days. These results indicate that early-morning training sessions severely
      restrict the amount of sleep obtained by elite athletes. Given that chronic sleep
      restriction of <6 h per night can impair psychological and physiological
      functioning, it is possible that early-morning schedules actually limit the
      effectiveness of training.

PMID- 24444224
TI  - Effects of a defender on run-up velocity and ball speed when crossing a football.
AB  - This study evaluated effects of defensive pressure on running velocity in
      footballers during the approach to kick a stationary football. Approach velocity
      and ball speed/accuracy data were recorded from eight football youth academy
      participants (15.25, SD=0.46 yrs). Participants were required to run to a
      football to cross it to a receiver to score against a goal-keeper. Defensive
      pressure was manipulated across three counterbalanced conditions: defender-absent
      (DA); defender-far (DF) and defender-near (DN). Pass accuracy (percentages of a
      total of 32 trials with 95% confidence limits in parenthesis) did not
      significantly reduce under changing defensive pressure: DA, 78% (55-100%); DF,
      78% (61-96%); DN, 59% (40-79%). Ball speed (m . s(-1)) significantly reduced as
      defensive pressure was included and increased: DA, 23.10 (22.38-23.83); DF, 20.40
      (19.69-21.11); DN, 19.22 (18.51-19.93). When defensive pressure was introduced,
      average running velocity of attackers did not change significantly: DA versus DF
      (m . s(-1)), 5.40 (5.30-5.51) versus 5.41 (5.34-5.48). Scaling defender starting
      positions closer to the start position of the attacker (DN) significantly
      increased average running velocity relative to the DA and DF conditions, 5.60
      (5.50-5.71). In the final approach footfalls, all conditions significantly
      differed: DA, 5.69 (5.35-6.03); DF, 6 .22 (5.93-6.50); DN, 6.52 (6.23-6.80). Data
      suggested that approach velocity is constrained by both presence and initial
      distance of the defender during task performance. Implications are that the
      expression of kicking behaviour is specific to a performance context and some
      movement regulation features will not emerge unless a defender is present as a
      task constraint in practice.

PMID- 24444225
TI  - Influence of gender and types of sports training on QT variables in young elite
      athletes.
AB  - Influence of gender and sports training on QT variables such as QT interval and
      dispersion (QT dispersion: QTD) in young elite athletes were evaluated. Subjects
      included 104 male and 97 female Japanese elite athletes (mean age 21.6 years).
      Sports included basketball, fencing, gymnastics, judo, swimming, tennis, track
      and field and volleyball. Age-matched healthy non-athletes (32 men and 20 women)
      were enrolled as controls. QT measurements were manually obtained from a 12-lead
      resting electrocardiogram and QTD was calculated as the difference between the
      longest and shortest QT intervals. A corrected QT interval (QTc) was obtained
      using Bazett's formula. Subjects were divided into two groups; an endurance
      training group and a static training group on the basis of their training types.
      RESULTS: Maximum and minimum QTc were significantly longer in female athletes
      than in male athletes (max: 414.2 vs. 404.5 ms, min: 375.1 vs. 359.2 ms, p<0.0001
      respectively), whereas QTc dispersion (QTcD) was shorter in female athletes than
      in male athletes (39.2 vs. 45.3 ms, p<0.0001). QTcD was significantly shorter in
      female athletes than in the female control group (39.2 vs. 45.2 ms, p<0.05).
      However, no statistically significant difference was observed between male
      athletes and the male control group. Male gymnasts exhibited significantly longer
      QTcD than the control group (p<0.01), but female gymnasts had significantly
      shorter QTcD than the control group (p<0.05). Maximum QTc intervals were
      prolonged in the male static training group compared with non-athletes, and QTcDs
      in the static training group were prolonged compared with the endurance training
      group. However, no significant difference was observed in the female group. In
      conclusion, both gender and different characteristics of sports training may
      affect QT variables even in young elite athletes. Vigorous static exercise
      training may independently prolong QT variables.

PMID- 24444226
TI  - The influence of socio-demographic indicators economic determinants and social
      recognition on sport participation in Germany.
AB  - This article analyses sport participation using a demographic-economic model
      which was extended by the construct 'social recognition'. Social recognition was
      integrated into the model on the understanding that it is the purpose of each
      individual to maximise his or her utility. A computer-assisted telephone
      interview survey was conducted in the city of Rheinberg, Germany, producing an
      overall sample of n=1934. Regression analyses were performed to estimate the
      impact of socio-demographic, economic determinants, and social recognition on
      sport participation. The results suggest that various socio-economic factors and
      social recognition are important determinants of sport participation on the one
      hand, and on sport frequency on the other. Social recognition plays a significant
      yet different role for both sport participation and sport frequency. While
      friends' involvement with sport influences one's sport participation, parents'
      involvement with sport influences one's sport frequency.

PMID- 24444227
TI  - Transcranial magnetic stimulation in sport science: a commentary.
AB  - The aim of this commentary is to provide a brief overview of transcranial
      magnetic stimulation (TMS) and highlight how this technique can be used to
      investigate the acute and chronic responses of the central nervous system to
      exercise. We characterise the neuromuscular responses to TMS and discuss how
      these measures can be used to investigate the mechanisms of fatigue in response
      to locomotor exercise. We also discuss how TMS might be used to study the
      corticospinal adaptations to resistance exercise training, with particular
      emphasis on the responses to shortening/lengthening contractions and
      contralateral training. The limited data to date suggest that TMS is a valuable
      technique for exploring the mechanisms of central fatigue and neural adaptation.

PMID- 24444228
TI  - Effects of a health-promotion programme in sixth grade German students' physical
      education.
AB  - The aim of the study was to assess the effects of a school-based health-promotion
      programme in physical education (PE) on sixth grade German students' motor
      performance, BMI and health-related quality of life (HRQOL). In a quasi
      experimental design, 516 students (54.7% girls) were assigned to either the
      intervention group (IG) that received eight 90-minute health-promoting PE lessons
      or the control group (CG), which continued regular PE. Outcome variables were
      assessed at baseline, immediately after, and three months after the intervention
      in order to explore significant short- and middle-term intervention effects,
      respectively. The intervention programme had gender specific effects in motor
      performance with girls reaching higher levels. Positive short-term intervention
      effects were found in girls' sideways jumps (eta (2)=0.17) and negative effects
      were measured in the 20-meter sprints (eta (2)=0.05) and the standing long jump
      (eta (2)=0.04). Positive middle-term effects were measured on the motor
      performance score (eta (2)=0.05), sideways jumps (eta (2)=0.08) and stand-and
      reach flexibility (eta (2)=0.04). In boys, short-term positive intervention
      effects were found in 20-meter sprints (eta (2)=0.04). In the middle-term,
      differences in favour of the CG were found in press-ups (eta (2)=0.03) and
      sideways jumps (eta (2)=0.06). Concerning BMI the IG had significantly lower
      levels compared to the CG in the short-term (eta (2)=0.04) and in the middle-term
      (eta (2)=0.03), respectively. There were no significant differences between the
      groups in HRQOL. In conclusion, the results demonstrate the feasibility of
      promoting health related parameters in PE, but also raise the question whether
      gender-specific tailored interventions would result in higher intervention
      effects concerning motor performance especially in boys.

PMID- 24444229
TI  - Portuguese adults' physical activity during different periods of the year.
AB  - This study aims to describe the daily physical activity (PA) of a sample of
      adults over the course of 1 year and to examine if there are any changes in
      achieving PA recommendations when assessed at different periods of the year.
      Participants, 257 women (age: 58.99 +/- 18.93 years, BMI: 26.75 +/- 4.57 kg m(
      2)) and 178 men (age: 49.22 +/- 20.39 years, BMI: 26.81 +/- 3.51 kg m(-2)), wore
      an accelerometer 4-7 days. Periods of data collection were defined as T1
      (September to December), T2 (January to April) and T3 (May to July). From T1 and
      T2, men from 20 to 39 years significantly increased values of daily average
      ct.min(-1) (U = 506, p = 0.012), due to an increase in moderate-to-vigorous PA by
      15.96 min (U = 455, p = 0.003). Achievement of the two PA recommendations varied
      throughout the year and among the gender/age groups. Results from this study
      showed that women generally maintain their level of PA throughout the year,
      whereas men show some variation, and that there are periods of the year when
      individuals are more likely to be involved in PA, or perform lower-intensity
      activities, especially older age groups. Also, recommendations of minimum PA are
      not accomplished in a constant way throughout the year. PA interventions should
      be conducted while being mindful of the time of year in which they will take
      place in order to help maintain a consistent PA level throughout the year to
      ensure health benefits from PA.

PMID- 24444230
TI  - Reliability and validity of the 7-day Physical Activity Recall interview in a
      Spanish population.
AB  - The aim of this study was to assess the reliability and convergent validity of
      the 7-day Physical Activity Recall (7-day PAR) interview in a sample of the
      Spanish population. Valid 7-day PAR interviews were conducted and RT3
      accelerometer measurements taken for 160 subjects from the primary care
      population aged 24-83, 75 men and 85 women. Two 7-day PAR interviews were
      conducted, with a one-week interval, with 147 of these participants. Test-retest
      reliability was assessed using intraclass correlation coefficients. Convergent
      validity between the 7-day PAR and the accelerometer data were examined using
      Spearman's correlation coefficients, and the kappa index of agreement was
      calculated. The 7-day PAR reliability coefficients were 0.68 (95%CI: 0.58-0.76)
      for total energy expenditure, 0.65 (95%CI: 0.54-0.73) for the activity dose, and
      0.61 (95%CI: 0.50-0.70) and 0.75 (95%CI: 0.67-0.81) for time spent on moderate
      and vigorous-intensity activity, respectively. These coefficients ranged from
      0.91 to 0.96 in participants who reported a typical week in both interviews.
      Convergent validity ranged from 0.25 for time spent on vigorous activity to 0.52
      for the activity dose, and the kappa index was 0.43 (95%CI: 0.30-0.56).
      Reliability and convergent validity coefficients in the Spanish population were
      generally moderate and similar to those found in other studies.

PMID- 24444231
TI  - Cricket team selection using data envelopment analysis.
AB  - This paper suggests a new method for cricket team selection using data
      envelopment analysis (DEA). We propose a DEA formulation for evaluation of
      cricket players in different capabilities using multiple outputs. This evaluation
      determines efficient and inefficient cricket players and ranks them on the basis
      of DEA scores. The ranking can be used to choose the required number of players
      for a cricket team in each cricketing capability. A real dataset, Indian Premier
      League 4 (IPL 2011), cricket players having various capabilities is used to
      choose the best cricket team. The proposed method has the advantage of
      considering multiple factors related to the performance of players in multiple
      capabilities collected from IPL 4 and aggregates their scores using a linear
      programming DEA model. This DEA Aggregation gives the scores of players
      objectively instead of using subjective computations. The proposed DEA method can
      be used to form a national cricket team from several clubs or a team of top
      cricketers.

PMID- 24444232
TI  - Peak acceleration during impact with helmet materials: effects of impactor mass
      and speed.
AB  - The impact properties of six foam materials used for energy absorption as the
      liner of children's helmets, reported by Gimbel and Hoshizaki are considered
      further. In high-energy impacts, almost complete compression of the energy
      absorbing material (bottoming out) may occur, and the severity of the impact
      increases greatly. Too soft a material means bottoming out occurs at low speeds,
      but if it is too stiff, the material itself is injurious. The fitting of
      equations to results in 'no bottoming out' and 'bottoming out' conditions may
      help assessment of what compromise is appropriate. The equations in this article
      correspond to peak acceleration being proportional to power functions of impactor
      speed and mass. 1. When there was no bottoming out, peak acceleration was found
      to be proportional to m (?)(c-1).v (?)(2c), with c being approximately 0.25. 2.
      For bottoming out, peak acceleration was found to be proportional to m (?)(p).v
      (?)(q), with p and q being approximately 2 and approximately 3. 3. The constants
      of proportionality were related to material density in a regular way.

PMID- 24444233
TI  - Considering long-term sustainability in the development of world class success.
AB  - The developmental practice patterns leading to the highest levels of success
      remain a subject of debate. The present study purposes to extend the body of
      empirical research by analysing athletic biographies from a large sample of
      German national squad athletes across all Olympic sports (n=1558; 57% male, 43%
      female). In a combined retrospective and longitudinal study utilising postal
      questionnaires, we evaluated the age at onset, volume, domain-specificity,
      variability in training and competition and success attained at different ages.
      Developmental practice patterns leading to rapid adolescent success and long-term
      senior success were inconsistent, and in some aspects contradictory. An early
      start-age for training and competition, early specialisation, high-intensity
      specific practice in the respective domain sport and little or no involvement in
      other sports (OS) favoured early adolescent success. Juvenile success, however,
      did not contribute to individual differences in success achieved at a senior age
      (-0.09<r s <0.03). Senior world class performers differed from national class
      athletes in a later age for onset of training and competition in their domain
      sport, later specialisation (14.4 vs. 12.1 years), more involvement in OS
      (training 66% vs. 51%; competitions 53% vs. 39%), but not in practice volume in
      their domain sport at any age. Findings were confirmed with longitudinal testing
      and were widely consistent across types of sports. These findings are interpreted
      relative to correspondence to deliberate practice and DMSP frameworks while
      drawing on the concept of long-term sustainability.

PMID- 24444234
TI  - Association between traditional standing vertical jumps and a soccer-specific
      vertical jump.
AB  - The present study aimed to determine the relationships between a soccer-specific
      vertical jump (ssVJ) test, that included common elements of a soccer VJ (e.g. run
      up and intention to head), and three traditional VJ tests using elite soccer
      players. A secondary purpose of this study was to determine the reliability of
      the VJs used in the analysis. A randomised order and counterbalanced design was
      used to assess the relationships between these VJs [countermovement jump (CMJ),
      drop jump for height (DJh), drop jump for maximum height and minimum ground
      contact time (DJh/t) and the ssVJ]. Take-off velocity, contact time and flight
      time were the dependent variables of interest and compared between jumps. Intra
      class correlation coefficient (ICC) and coefficient of variation (CV) were used
      as measures of inter-session reliability. All VJ tests were found to have high
      ICCs (0.89-0.99) and acceptable within-subject CVs (<7.5%). All the ssVJ
      dependent variables were not significantly related (r<0.44) with similar
      variables from the CMJ and DJh tests and only moderately related (r=~0.49) with
      the DJh/t test variables. In addition, the DJh/t variables were not significantly
      correlated (r<0.47) with DJh and CMJ test variables. In conclusion, it would seem
      that the proposed ssVJ test and CMJ or DJh tests assess different leg qualities
      and thought should be given before using them interchangeably to assess or
      develop the same performance measures (i.e. velocity at take-off or jump height).

PMID- 24444235
TI  - Time-variant modelling of heart rate responses to exercise intensity during road
      cycling.
AB  - The aim of this study was to determine if heart rate responses to training
      intensity during road cycling could be modelled with compact time-variant
      mathematical model structures. The model performance was evaluated in terms of
      model order (complexity), number of inputs and parameter estimation methods used
      (time-invariant vs. time-variant). Thirteen male cyclists performed two identical
      cycling tests of 27 km on the road. Uphill sections were introduced to induce
      dynamic variations in heart rate. The heart rate and training intensity,
      represented by power output and road inclination, were measured in real-time.
      Taking only power as system input allowed to explain the variations in heart rate
      in an accurate way R2 T = 0.86 +/- 0.08, since adding the road inclination as an
      additional input did not significantly improve the modelling performance R2 T =
      0.87 +/- 0.08, P = 0.32. Furthermore, we demonstrated that models with first
      order dynamics accurately describes the heart rate responses to power variations
      R2 T = 0.86 +/- 0.08, but that more complex second-order model structures R2 T =
      0.88 +/- 0.08 were significantly better than the first-order model structures (P
      = 0.028). Finally, the heart rate dynamics appeared to be time-variant, since the
      time-variant model structures R2 T = 0.89 +/- 0.07 were significantly better than
      the time-invariant model structures R2 T = 0.84 +/- 0.08, P = 0.0002. So, compact
      time-variant second-order model structures could be used to model the heart rate
      response to training intensity as a basis for training optimisation.

PMID- 24444236
TI  - Effects of body positions on the saddle on pedalling technique for cyclists and
      triathletes.
AB  - Cyclists usually change their body position on the saddle depending on the
      characteristics of the race. We compared the effects of cycling at three body
      positions on the saddle (preferred/self-selected, most forward, most backward) on
      pedalling technique for cyclists and triathletes. Twelve cyclists and nine
      triathletes performed four trials starting with the maximal aerobic workload,
      followed by three trials at the workload of their ventilatory threshold. Force
      applied on the right pedal via an instrumented pedal, lower limb kinematics via
      video and muscle activation via electromyography were recorded during all trials.
      Pedalling technique was quantified using total force applied on the pedal, pedal
      force effectiveness, activation of six lower limb muscles, joint angles and
      mechanical work at the ankle, knee and hip joints. Analyses using effect sizes
      showed no large effects from changes in position on the saddle for pedal forces,
      ankle joint work and ankle kinematics. There were large increases in knee joint
      angle and mechanical work and rectus femoris activation along with smaller hip
      work at the forward position on the saddle. Differences between cyclists and
      triathletes were not substantial. Effects of changes in saddle positions were
      limited to the hip and knee joints.

PMID- 24444237
TI  - Fluid balance of cyclists during a 387-km race.
AB  - Current hydration guidelines are designed to address the fine balance between
      minimising dehydration while reducing the risk of hyponatremia. During prolonged
      cycling events small discrepancies between drinking behaviour and fluid
      requirements may be detrimental to health and performance. The present study
      aimed to investigate the hydration practices of competitors in a 387 km cycle
      race in order to evaluate the effect on fluid balance and monitor the prevalence
      of dysnatremia. Eighteen participants provided blood and urine samples pre- and
      post-race to measure sodium and fluid balance. Sweat samples were collected via
      patches for analysis of sodium concentration. Body weight was measured at the
      start and end of the race. On average participants consumed 0.58 L h(-1) of
      fluid. Upon completion of the race 7 of the 18 (39%) cyclists had blood sodium
      concentrations of 135 mmol L(-1) or lower with one cyclist recording a value of
      132 mmol L(-1). Only two cyclists appeared to be moderately dehydrated. A post
      race questionnaire indicated cyclists were most concerned with preventing
      dehydration. It appears that cyclists taking part in prolonged endurance events
      are at more risk of hyponatremia than dehydration and do not readily change their
      drinking behaviour to match their sweat losses.

PMID- 24444238
TI  - Physiological characteristics of elite dancers of different dance styles.
AB  - The present investigation was aimed to study international level dancesport
      dancer's aerobic capacity during incremental test and competition simulation in
      relation to the gender, dance style and international ranking. A total of 30
      couples (12 Standard, 7 Latin American and 11 Ten Dance; aged 22.8 +/- 6.6 years
      male and 22.0 +/- 6.4 years female) performed an incremental treadmill test and
      competition simulation. In this study for the first time we carried out longer
      than one round competition simulation and compared three different dancesport
      styles (Standard, Latin American and Ten Dance). The results showed that dancers
      of these three dance styles had similar aerobic capacity values. The average
      maximal oxygen consumption (VO2max) values were 59.6 +/- 5.1 and 51.2 +/- 6.2 ml
      . min(-1) . kg(-1) for male and female dancers, respectively. Competition
      simulation showed that Latin American Dance discipline is physiologically more
      intensive compared to Standard and Ten Dance styles especially for the female
      dancers. It appeared that male and female Standard dancers tended to perform at
      lower intensity than anaerobic threshold (AT) during competition simulation (male
      97.3 +/- 2.9%; female 97.9 +/- 3.6%), while Latin (male 101.4 +/- 2.9%; female
      106.7 +/- 5.9%) and Ten Dance (male 100.7 +/- 6.4%; female 99.2 +/- 5.6%)
      competition intensity was higher compared to AT level of athletes. The highest
      heart rate during competition simulation was always found during the last dances
      (Paso Double, Jive or Quickstep) and in the last round of each dance style. No
      significant relationship between VO2max values and international rankings was
      registered.

PMID- 24444239
TI  - Artificial turf surfaces: perception of safety, sporting feature, satisfaction
      and preference of football users.
AB  - The aim of this research is to understand the experience of the football sector
      on the use of artificial turf (satisfaction, safety, sporting feature, or the
      advantages and disadvantages). The study was conducted on a random selection of
      627 male participants (404 amateur/semi-professional footballers, 101 coaches and
      122 referees) that regularly train/compete on artificial turf in Spanish football
      leagues. The results of the skin abrasion, muscle strain and the possibility of
      sustaining an injury, on a Likert-type 10-point interval scale, gave a perception
      of 'somewhat dissatisfied' for the participants. The main advantages of
      artificial turf were their sports features, the evenness of the surface and the
      good state of conservation. Participants were satisfied with the artificial turf
      surface. Approximately three out of four participants gave an overall ranking of
      highly satisfied. The players were significantly less satisfied than the coaches
      and referees. The overall satisfaction with artificial turf fields was strongly
      influenced by previous experience, particularly those who had previously played
      on dirt pitches. These results highlight the versatility of artificial turf to
      adapt to any circumstance or requirement for local sport and top-level
      professional competitions alike.

PMID- 24444240
TI  - Athletes' expectations with regard to officiating competence.
AB  - This study aimed to identify the cues upon which athletes rely when developing
      their expectations with regard to the competence of sports officials and to
      examine the sources of information, which are given priority in different kinds
      of sport (i.e. team, racquet and fighting sports). A questionnaire - the Athlete
      Perception of Sports Officials Questionnaire (APSO-Q) - was developed in which
      athletes (N=472) were asked to indicate the influence of 32 cues on their
      impressions of sports officials. Exploratory factor analysis (EFA) yielded a four
      factor model (i.e. static cues, psychological, communicational and performance
      cues). Athletes mostly rely on psychological and personal communication
      attributes when evaluating officiating competence. Moreover, team players
      perceived that static cues were more influential when forming their expectations
      of sports officials than racquet players and fighting contestants. Such findings
      may have implications for athlete-official relationships and training of sports
      officials.

PMID- 24444241
TI  - Relative-age effect on competition outcomes at the World Youth and World Junior
      Athletics Championships.
AB  - The relative-age effect refers to a higher frequency of athletes with birthdates
      earlier in the competitive year. Track and field athletics has a 2-year
      competitive cycle at youth and junior levels that could make it particularly
      susceptible to the effect. We have therefore investigated the effect in athletics
      event finalists (first to eighth place) at the 2008 Junior Championships (men and
      women aged <= 19 years; n=1479) and the 2009 Youth Championships (boys and girls
      aged 16-17 years; n=1445). Counts of finalists differing in age by 1 year were
      estimated with Poisson regression and compared as factor effects (with *// 90%
      confidence limits and assessment of magnitude). The factor effects were: junior
      men 2.1 (*// 1.4, large); junior women 1.7 (*// 1.4, moderate); youth boys 3.7
      (*// 1.4, very large); youth girls 2.1 (*// 1.3, large). Analysis by event group
      indicated the age effect was greatest in youth boys' sprints & hurdles (4.0, *//
      1.7, very large), throws (7.2, *// 2.3, very large) and jumps (5.6, *// 1.9, very
      large), whereas it was smallest in junior men's throws (1.4, *// 1.4, small) and
      youth girls' jumps (1.4, *// 1.4, small). In conclusion, the marked relative-age
      effects in athletics must exclude some talented younger athletes from youth and
      junior championships and presumably discourage them from continuing to senior
      championships. The consequences are a lower overall standard of performance and,
      for some athletes, termination of involvement in athletics before realising their
      full potential. An alternative structure and calendar is needed to make youth and
      junior athletics championships more equitable.

PMID- 24444242
TI  - The reliability of tests for sport-specific skill amongst elite youth rugby
      league players.
AB  - In rugby league, tests of sport-specific skill often involve subjective
      assessments of performance by observers of varying qualification. However, the
      reliability of such subjective assessments has yet to be investigated via
      appropriate statistical techniques. Therefore, the aims of the current study were
      to investigate: (1) the intra-observer reliability of a non-qualified observer
      ('novice') and (2) the inter-observer reliability of the three observers (two
      qualified 'experts' and one novice observer) in the assessment of catching,
      passing and tackling (stages 1 and 2) ability in elite adolescent rugby league
      players (age: 14.7 +/- 0.5 years). Players performed each skill element within a
      simulated practice drill and were assessed in 'real time' by the observers
      according to pre-defined criteria. An overall bias (P<0.05) was revealed between
      the observers in stage 1 of catching and stage 1 of passing, the differences
      being higher for the novice compared to both expert coaches for each stage of
      catching and the first stage of passing, and between expert 2 and the novice for
      stage 2 of tackling. No comparisons met the pre-determined analytical goal of
      'perfect agreement', for any of the skill components. Comparisons between the
      expert observers did not reach perfect agreement, with the lowest values
      occurring for both tackling skill stages (60-65%). None of the tests employed
      were sufficiently reliable to potentially discern between players of differing
      ability, which may mean up to 56% of players' skill being misinterpreted. The
      credibility of such assessments should be questioned and alternative tests
      considered.

PMID- 24444243
TI  - The effect of performance context and skill level on the frequency of flow
      experiences.
AB  - The main purpose of this study was to examine interaction effects between skill
      level and performance contexts on the experience of flow in adolescent tennis
      players. The study employed a factorial design to examine differences in flow
      frequency between competition and training settings and the independent groups
      factor of ranking list and club players. Junior tennis players (55 males, 29
      females) completed the Dispositional Flow Scale-2 in training and competition
      settings. A repeated-measure ANCOVA, with years of tennis experience and training
      hours per week as covariates, showed a significant main effect for skill level,
      F(1, 82) = 6.67, p<0.05, eta2 p = 0.08, a significant main effect for performance
      contexts, F(1, 82) = 7.69, p < 0.01, eta2 p = 0.09, and a significant disordinal
      interaction, F(1, 82) = 9.93, p < 0.01, eta2 p = 0.11. Lower skilled athletes
      experienced flow with similar frequency across performance contexts, whereas
      advanced players experienced flow more often during training than competition.
      Qualitative results showed that club players' involvement in both performance
      contexts was mainly based on intrinsic reasons, whereas ranking list players
      reported intrinsic reasons for training, but a high number of extrinsic reasons
      for competition. Future studies should take propositions of the flow model into
      account in order to advance theoretical developments on interaction effects and
      shed more light into the complex processes underlying flow in sport.

PMID- 24444244
TI  - Length, width and centroid distance as measures of teams tactical performance in
      youth football.
AB  - Small-sided games are commonly used in training and teaching contexts of
      football. However, few studies have focused on the tactical implications of this
      type of drills. The aim of this study is to identify how tactical collective
      behaviour varies with age in different small-sided game formats. We investigated
      the in-game field position in three different age groups of youth football
      players [under-9 (n=10; age = 8.5 +/- 0.53), under-11 (n=10; age = 10.4 +/- 0.52)
      and under-13 (n=10; age = 12.7 +/- 0.48)], participating in two different small
      sided game conditions (GK + 3 * 3 + GK and GK + 4 * 4 + GK). A team variable was
      created based on the players' length per width ratio (lpwratio), and a match
      variable was calculated as the distance between the centroid of the two teams.
      Results show that team variable values were influenced by the age of the players,
      as younger teams tend to present a higher value of lpwratio in their dispersion
      on the pitch. The variability of this variable also showed a decrease for teams
      with older players, suggesting a more consistent application of the width
      (stretching and creating space) and concentration (compressing into a confined
      area) principles of play and reflecting a higher level of collective tactical
      behaviour. Match variable showed a larger centroid distance for the older age
      groups in comparison with the younger players in the GK + 3 * 3 + GK, while all
      age groups demonstrated similar large centroid distances in the GK + 4 * 4 + GK
      game format. These results suggest that length and width ratio and centroid
      distance are useful measures of tactical performance in small-sided games in
      youth football.

PMID- 24444245
TI  - The influence of training status on the aerobic and anaerobic responses to
      exercise in children: a review.
AB  - Exercise training represents a potent stimulus to the development of aerobic and
      anaerobic fitness in adults; whether the same is true in young children is
      unclear. With the possible exception of peak VO2, many parameters of aerobic and
      anaerobic fitness remain scarcely investigated in children, especially pubertal
      children. Despite this lack of empirical evidence, it has been suggested that
      children may lack trainability and that this may be related to the presence of a
      maturational threshold below which significant adaptations to training cannot
      occur. This suggestion requires investigation, not least because the findings of
      some studies which appear to support this contention may in reality be a
      reflection of the use of an inappropriate test modality or training programme for
      the investigation of training status influences. The purpose of this review is
      therefore to provide insight into the current consensuses and controversies
      regarding the influence of training in young people.

PMID- 24444246
TI  - Perceptions of team athletes on the importance of recovery modalities.
AB  - The aim of this study was to determine how elite team athletes perceive the
      importance of various recovery modalities. Differences between men and women,
      players from various team sports and different levels of participation were
      determined. A total of 890 athletes who volunteered to participate in the study
      were team players from field hockey (n = 213; mean age 21.8 +/- 3.3 years),
      netball (n = 215; mean age 22.0 +/- 4.0 years), rugby union (n = 317; mean age
      23.2 +/- 3 years) and soccer (n = 145; mean age 21.3 +/- 2.2 years). The total
      group of players consisted of 507 (57%) men and 383 (43%) women. At the time of
      the study, players who participated in the study competed at the highest level of
      the major competitions and tournaments in their sport, both locally and
      internationally. Data were collected by means of a questionnaire specifically
      designed for the study. A one-page, alphabetical list consisted of 32 words or
      phrases relating to physiological, psychological, social as well as complimentary
      and alternative strategies, which could be used for the recovery of athletes.
      Recovery modalities that were rated as important by all players, regardless of
      gender, type of sport or level of participation, were sleep, fluid replacement
      and socialise with friends. Gender differences could play a role in how the
      importance of recovery modalities was perceived. Men rated an ice bath and
      supplements as significantly more important (P<0.001) than women. Women rated
      discussions with their teammates and coaches after training and matches as
      significantly more important (P<0.001) than men. Significant differences were
      also found between the different sport codes and levels of participation in
      regard to the perceived importance of various modalities that could affect
      recovery of team sport players.

PMID- 24444247
TI  - Comparison of home advantage in men's and women's football leagues in Europe.
AB  - Most research into home advantage is based on men's sports. This article analyses
      home advantage in the women's domestic football leagues of Europe and makes a
      comparison with the corresponding men's football leagues. A total of 47,042 games
      were included. From 2004 to 2010, home advantage existed in the domestic women's
      soccer leagues of all 26 European countries analysed, ranging from 51.0% to 58.8%
      and averaging 54.2%. In every country, this was less than the corresponding men's
      home advantage which averaged 60.0%. Crowd effects, both on players and referees,
      and different gender perceptions of territorial protection are plausible reasons
      for the differences found. Using a regression model that controlled for the
      competitive balance of each league, as well as for crowd size, the Gender Gap
      Index, which quantifies the status of women in each country, was a significant
      predictor of the difference between men's and women's home advantage. As the
      status of women becomes closer to that of men within a country, the difference in
      home advantage is less between the men's and women's football leagues.

PMID- 24444248
TI  - The relationship between physical fitness and game behaviours in rugby union
      players.
AB  - The physical preparation of team sport athletes should reflect the degree to
      which each component of fitness is relied upon in competition. The aim of the
      study was therefore to establish the relationship between fitness-test data and
      game behaviours known or thought to be important for successful play in rugby
      union matches. Fitness-test measures from 510 players were analysed with game
      statistics, from 296 games within the 2007 and 2008 calendar years. Sprint times
      over 10, 20 and 30 m had moderate to small negative correlations (r) with line
      breaks (~0.26), metres advanced (~0.22), tackle breaks (~0.16) and tries scored
      (~0.15). The average time of 12 repeated sprints and percentage body fat in the
      forwards, and repeated sprint fatigue in the backs had moderate to small
      correlations with a measure of activity rate on and around the ball (-0.38, -0.17
      and -0.17, respectively). These low correlations are partly due to uniformly high
      physical fitness as a result of selection pressures at the elite level and leave
      room for the identification of other key predictors. Nonetheless, physical
      conditioning programmes should be adapted to reflect the importance of speed,
      repeated sprint ability and body composition in the performance of key game
      behaviours during competition.

PMID- 24444249
TI  - Effects of different precooling techniques on repeat sprint ability in team sport
      athletes.
AB  - This study aimed to compare the simultaneous use of internal and external
      precooling methods with singular methods and their effect on repeated sprint
      cycling in hot/humid conditions. Twelve male team sport players completed four
      experimental conditions, initially involving a 30-min precooling period
      consisting of either a cooling jacket (J); ingestion of an ice slushy ice slushy;
      combination of cooling jacket and ice ingestion (J + ice slushy); or control
      (CONT). This was followed by 70 min of repeat sprint cycling (in~35 degrees C,
      60% relative humidity [RH]), consisting of 2 * 30-min halves, separated by a 10
      min half-time period where the same cooling method was again used. Each half
      comprised 30 * 4 s maximal sprints on 60 s, interspersed with sub-maximal
      exercise at varying intensities. Total mean power and work performed were
      significantly higher (p = 0.02) in J + ice slushy (233.6 +/- 31.4 W) compared to
      ice slushy (211.8 +/- 34.5 kJ), while moderate effect sizes (ES: d = 0.67)
      suggested lower core temperatures (TC) in J + ice slushy (36.8 +/- 0.3 degrees C)
      compared to J (37.0 +/- 0.3 degrees C) and CONT (37.0 +/- 0.3 degrees C)
      following precooling. A moderate ES (d = 0.57) also indicated lower TC in J + ice
      slushy (38.2 +/- 0.3) compared to ice slushy (38.4 +/- 0.4 degrees C) after half
      time cooling. Change (Delta) in mean skin temperature over half-time cooling was
      significantly greater (p = 0.036) for J (1.0 +/- 0.4 degrees C) compared to ice
      slushy (0.5 +/- 0.5 degrees C), and ES (d = 0.5-1.10) also suggested a greater
      Delta for J compared to the other conditions. Sweat loss was significantly
      greater (p < 0.05) in ice slushy and J + ice slushy compared to J and CONT. In
      conclusion, a combination of (external and internal) body cooling techniques may
      enhance repeated sprint performance in the heat compared to individual cooling
      methods.

PMID- 24444250
TI  - The effects of running a 308 km ultra-marathon on cardiac markers.
AB  - The aim of this study was to investigate the expression of cardiac strain and
      damage in 18 male marathoners with average age of 52.8 +/- 5.0 years running at a
      308 km ultra-marathon. Blood samples were collected at pre-race, 100 km, 200 km
      and 308 km check points for the analysis of cardiac muscle injury markers,
      creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponin I
      (cTnI) and cardiac muscle strain marker, N-terminal pro-brain natriuretic peptide
      (NT-proBNP). The CK levels increased 1127.2 +/- 507.9 IU/L, 5133.8 +/- 2492.7
      IU/L and 4958.4 +/- 2087.9 IU/L at 100 km, 200 km and 308 km, respectively,
      compared to the pre-race levels. The CK-MB levels increased 20.2 +/- 11.2 ng/mL,
      73.3 +/- 35.6 ng/mL and 68.6 +/- 42.6 ng/mL at 100, 200 and 308 km, respectively,
      compared to the pre-race levels. The CK-MB/CK ratio showed that the CK-MB mass
      index was within the normal range (<2.5%) at 100 km, 200 km and 308 km. The cTnI
      levels showed no significant difference in all check points. The NT-proBNP levels
      increased 146.55 +/- 92.7 pg/mL, 167.95 +/- 111.9 pg/mL and 241.23 +/- 121.2
      pg/mL at 100, 200 and 308 km, respectively, compared to the pre-race levels. The
      normal CK-MB mass index (<5.0 ng/mL) and the absence of an increase in the cTnI
      levels during the 308 km ultra-marathon suggested that no myocardial injury
      despite an elevation in CK-MB. The increase in NT-proBNP levels probably resulted
      from continuous hemodynamic cardiac stress and represents a transient
      physiological myocardial protective response.

PMID- 24444251
TI  - Inactivity-induced oxidative stress: a central role in age-related sarcopenia?
AB  - Ageing causes a progressive decline in skeletal muscle mass that may lead to
      decreased strength and functionality. The term sarcopenia is especially used to
      characterise this geriatric syndrome. Numerous conditions and behaviours are
      considered to accelerate the progression of sarcopenia such as chronic diseases,
      malnutrition and physical inactivity. As people in modern countries are more and
      more sedentary, the impact of physical inactivity on the prevalence of sarcopenia
      might be more and more important in the future. In this review, we discuss how
      reactive oxygen species (ROS) could mediate the effects of lifelong inactivity in
      the onset and progression of age-related sarcopenia. Although the cellular
      mechanisms responsible for muscle ROS production are not necessarily the same,
      both inactivity and ageing are indeed known to increase basal ROS concentrations
      in skeletal muscle. New data and literature review are provided showing that
      chronic ROS overproduction induced by physical inactivity may exacerbate the
      activation of some redox-sensitive signalling pathways involved in age-related
      sarcopenia. We also address the scientific evidences implicating the role of ROS
      overproduction in the precocious failure of aged muscles to activate
      intracellular signalling responses to contractions.

PMID- 24444252
TI  - Connectedness and suicide prevention in adolescents: pathways and implications.
AB  - Adolescent suicide is a major public health concern. Stressing the need for
      public health-based solutions, the Centers for Disease Control and Prevention
      identified "connectedness" as one means of pursuing this agenda. To advance this
      effort in suicide prevention with adolescents, (1) consistencies and variation in
      the literature overtly linking connectedness to suicide thoughts and behaviors
      (STB) are reviewed, (2) three more specific mechanistic pathways are proposed
      whereby connectedness may influence STB, and (3) several implications related to
      use of connectedness as a public health framework for adolescent suicide
      prevention and intervention are outlined. 

PMID- 24444253
TI  - Down-regulation of MET in hippocampal neurons of Alzheimer's disease brains.
AB  - We found that mRNA of MET, the receptor of hepatocyte growth factor (HGF), is
      significantly decreased in the hippocampus of Alzheimer's disease (AD) patients.
      Therefore, we tried to determine the cellular component-dependent changes of MET
      expressions. In this study, we examined cellular distribution of MET in the
      cerebral neocortices and hippocampi of 12 AD and 11 normal controls without brain
      diseases. In normal brains, MET immunoreactivity was observed in the neuronal
      perikarya and a subpopulation of astrocytes mainly in the subpial layer and white
      matter. In AD brains, we found marked decline of MET in hippocampal pyramidal
      neurons and granule cells of dentate gyrus. The decline was more obvious in the
      pyramidal neurons of the hippocampi than that in the neocortical neurons. In
      addition, we found strong MET immunostaining in reactive astrocytes, including
      those near senile plaques. Given the neurotrophic effects of the HGF/MET pathway,
      this decline may adversely affect neuronal survival in AD cases. Because it has
      been reported that HGF is also up-regulated around senile plaques, beta-amyloid
      deposition might be associated with astrocytosis through the HGF signaling
      pathway. 

PMID- 24444254
TI  - Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like
      diuretics.
AB  - INTRODUCTION: Thiazides and thiazide-like diuretics inhibit the electroneutral
      Na(+)-Cl(-) cotransporter located on the apical membrane of the early segment of
      the distal convoluted tubule. They have been widely prescribed over 60 years in
      the treatment of hypertension and various edematous states. AREAS COVERED:
      Thiazide diuretics reduce blood pressure (BP), although the mechanisms by which
      they chronically lower BP remain unknown. These drugs present a flat dose
      response curve that explains why when prescribed at high doses their use was
      associated with a wide range of adverse effects, particularly electrolyte changes
      and metabolic abnormalities that can be minimized at the low doses actually
      prescribed. This article reviews the clinical pharmacology of thiazide diuretics
      to provide an insight into the mechanisms involved in their antihypertensive and
      adverse effects, the determinants of drug response and the possible differences
      in their pharmacodynamic and pharmacokinetic properties in an attempt to improve
      their clinical use in the treatment of arterial hypertension. EXPERT OPINION: At
      low doses, thiazide diuretics remain as an effective and safe therapeutic
      alternative in the treatment of hypertension. Additionally, their ability to
      increase the efficacy of nearly all other classes of antihypertensives makes them
      a highly versatile therapeutic intervention in the treatment of hypertension.

PMID- 24444255
TI  - Effects of rhaponticum carthamoides versus glycyrrhiza glabra and punica granatum
      extracts on metabolic syndrome signs in rats.
AB  - BACKGROUND: Rhaponticum cathamoides (RC) is an endemic wild Siberian herb with
      marked medicinal properties that are still poorly understood. The aim of this
      study is to investigate the therapeutic potential of RC extract (ERC) compared to
      the effects of Glycyrrhiza glabra (EGG) and Punica granatum extracts (EPG) in a
      rat model with high-fat diet-(HFD)-induced signs of metabolic syndrome;
      therefore, this study addresses a significant global public health problem.
      METHODS: Six-month-old male Wistar Albino Glaxo rats were subjected to eight
      weeks of a standard diet (SD), HFD, or HFD in which ERC, EGG, or EPG powders were
      incorporated at 300 mg/kg/day. The serum lipid profile, corticosterone and
      cytokine concentrations, glucose tolerance, systolic blood pressure,
      triacylglycerol accumulation, and PPARalpha DNA-binding activities in the liver
      samples were determined. RESULTS: In contrast to EGG and EPG, an ERC supplement
      significantly reduced the weight of epididymal tissue (19.0%, p < 0.01) and basal
      serum glucose level (19.4%, p < 0.05). ERC improved glucose intolerance as well
      as dyslipidemia more efficiently than EGG and EPG. EGG but not ERC or EPG
      supplementation decreased systolic blood pressure by 12.0% (p < 0.05). All of the
      tested extracts reduced serum IL6 and corticosterone levels induced by HFD.
      However, the lowering effects of ERC consumption on the serum TNF-alpha level and
      its restoring effect on the adrenal corticosterone level significantly exceeded
      the improvements induced by EGG and EPG. ERC intake also reduced triacylglycerol
      accumulation and increased the PPARalpha DNA-binding activity in the liver more
      significantly than EGG and EPG. CONCLUSIONS: ERC powder supplementation improved
      glucose and lipid metabolism more significantly than EGG and EPG in rats fed on
      HFD, supporting the strategy of R. carthamoides use for safe relief of metabolic
      syndrome and its related disturbances such as inflammation, stress, and hepatic
      steatosis.

PMID- 24444257
TI  - Radiography-based score indicative for the pathogenicity of bacteria in
      odontogenic infections.
AB  - OBJECTIVE: To develop a new radiography-based score to assess the potential of
      bacteria to cause odontogenic infections derived from the occurrence of bacteria
      at small or large radiographical lesions. MATERIALS AND METHODS: The patients
      analyzed were a sub-population from a large randomized clinical trial comparing
      moxifloxacin and clindamycin in the treatment of inflammatory infiltrates and
      odontogenic abscesses. Routine radiographs were used to analyze the area of the
      periapical radiolucent lesions. Lesions were stratified by their radiographically
      measured area as large (>9 mm(2)) or small (<=9 mm(2)). A risk ratio was
      calculated for each species from the frequency of their occurrence in large vs in
      small lesions. RESULTS: Fifty-one patients, 19 with abscesses and 32 with
      infiltrates, were evaluated. Overall, the radiographical lesion areas ranged from
      0.4-46.2 mm(2) (median = 9 mm(2)). An increased risk (risk ratio >1) to occur at
      large abscess lesions was observed for Prevotella (P.) oralis, P. buccae, P.
      oris, P. intermedia, Fusobacterium nucleatum and Streptococcus (Strep.) anginosus
      group. An increased risk to occur at large infiltrate lesions was found for
      Strep. salivarius, Strep. parasanguis, Strep. anginosus group, Capnocytophaga
      spp., Neisseria (N.) sicca, Neisseria spp., Staphylococcus (Staph.) aureus, P.
      intermedia, P. buccae, Prevotella spp. and P. melaninogenica. CONCLUSIONS: The
      radiography-based score suggests that certain Prevotella spp., F. nucleatum and
      Strep. anginosus groups play a crucial role in the pathogenesis of odontogenic
      abscesses, and that various streptococci, Neisseria spp., Capnocytophaga spp.,
      Staph. aureus and Prevotella spp. are involved in the pathogenesis of odontogenic
      infiltrates.

PMID- 24444258
TI  - Statistical analysis of teeth autotransplantation in Portugal's region of Chaves.
AB  - AIM: The aim of this study was to evaluate the success rate of 33 transplanted
      teeth in a northern population of Portugal. METHODS: The mean follow-up period
      was 7 years, ranging from 6 months to 20 years. RESULTS: Six teeth (18%) were
      rated as unsuccessful, 52% of the donor teeth were transplanted to receptor
      alveolus after immediate exodontia and 24% were transplanted to receptor alveolus
      surgically prepared. From the total number of cases, 64% had open root apex at
      the time of the transplantation and, in the latest control, of all teeth root
      development was over in 55%. Teeth ankylosis was present in 38% of all cases and
      58% of all 33 transplants presented pulpar vitality. Data shows that, in males,
      teeth transplanted into natural alveolus were non-ankylosed, with normal color
      and vital teeth with incomplete root development at the time of the surgery. All
      cumulative curves obtained showed no statistical significance, mainly due to the
      low number of unsuccessful teeth autotransplantations. Orthodontic treatment
      performed after tooth autotransplantation showed success in 15% of all cases.
      CONCLUSION: Data reconfirms that autotransplantation of teeth is, in selected
      patients, the best option to replace a missing tooth in young patients.

PMID- 24444256
TI  - Regional mapping of myocardial hibernation phenotype in idiopathic end-stage
      dilated cardiomyopathy.
AB  - Myocardial hibernation (MH) is a well-known feature of human ischaemic
      cardiomyopathy (ICM), whereas its presence in human idiopathic dilated
      cardiomyopathy (DCM) is still controversial. We investigated the histological and
      molecular features of MH in left ventricle (LV) regions of failing DCM or ICM
      hearts. We examined failing hearts from DCM (n = 11; 41.9 +/- 5.45 years; left
      ventricle-ejection fraction (LV-EF), 18 +/- 3.16%) and ICM patients (n = 12;
      58.08 +/- 1.7 years; LVEF, 21.5 +/- 6.08%) undergoing cardiac transplantation,
      and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero
      lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and
      sub-endocardial layers) analysed. LV glycogen content was shown to be increased
      in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped
      transmural distribution (lower values in mesocardium). Capillary density was
      homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N),
      with a lower decrease independent of the extent of fibrosis in sub-endocardial
      and sub-epicardial layers of DCM as compared with ICM. HIF1-alpha and nestin,
      recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and
      ICM-LV myocardium. The proteomic profile was overlapping by ~50% in DCM and ICM
      groups. Morphological and molecular features of MH were detected in end-stage ICM
      as well as in end-stage DCM LV, despite epicardial coronary artery patency and
      lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of
      coronary stenosis may be helpful to design a novel approach in the clinical
      management of DCM.

PMID- 24444260
TI  - Entering 2014.

PMID- 24444259
TI  - Autologous circulating angiogenic cells treated with osteopontin and delivered
      via a collagen scaffold enhance wound healing in the alloxan-induced diabetic
      rabbit ear ulcer model.
AB  - INTRODUCTION: Diabetic foot ulceration is the leading cause of amputation in
      people with diabetes mellitus. Peripheral vascular disease is present in the
      majority of patients with diabetic foot ulcers. Despite standard treatments there
      exists a high amputation rate. Circulating angiogenic cells previously known as
      early endothelial progenitor cells are derived from peripheral blood and support
      angiogenesis and vasculogenesis, providing a potential topical treatment for non
      healing diabetic foot ulcers. METHODS: A scaffold fabricated from Type 1 collagen
      facilitates topical cell delivery to a diabetic wound. Osteopontin is a
      matricellular protein involved in wound healing and increases the angiogenic
      potential of circulating angiogenic cells. A collagen scaffold seeded with
      circulating angiogenic cells was developed. Subsequently the effect of autologous
      circulating angiogenic cells that were seeded in a collagen scaffold and
      topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan
      induced diabetic rabbit ear ulcer model was used to determine healing in response
      to the following treatments: collagen seeded with autologous circulating
      angiogenic cells exposed to osteopontin, collagen seeded with autologous
      circulating angiogenic cells, collagen alone and untreated wound. Stereology was
      used to assess angiogenesis in wounds. RESULTS: The cells exposed to osteopontin
      and seeded on collagen increased percentage wound closure as compared to other
      groups. Increased angiogenesis was observed with the treatment of collagen and
      collagen seeded with circulating angiogenic cells. CONCLUSIONS: These results
      demonstrate that topical treatment of full thickness cutaneous ulcers with
      autologous circulating angiogenic cells increases wound healing. Cells exposed to
      the matricellular protein osteopontin result in superior wound healing. The wound
      healing benefit is associated with a more efficient vascular network. This
      topical therapy provides a potential novel therapy for the treatment of non
      healing diabetic foot ulcers in humans.

PMID- 24444261
TI  - Pathologic and clinical characteristics of elderly patients with breast cancer: a
      retrospective analysis of a multicenter study (Anatolian Society of Medical
      Oncology).
AB  - There is very little information about breast cancer characteristics, treatment
      choices, and survival among elderly patients. The purpose of this multicenter
      retrospective study was to examine the clinical, pathologic, and biologic
      characteristics of 620 breast cancer patients age 70 years or older. Between June
      1991 and May 2012, 620 patients with breast cancer, recruited from 16
      institutions, were enrolled in the retrospective study. Patients had smaller
      tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number
      of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety
      three patients (15.0%) had metastatic disease at diagnosis. Patients were
      characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors
      of the elderly patients were also more frequently estrogen receptor (ER) positive
      (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic
      therapies for breast cancer differed according to age. An association between age
      and overall survival has not been demonstrated in elderly patients with breast
      cancer. In conclusion, the biologic behavior of older patients with breast cancer
      differs from younger patients, and older patients receive different treatments.

PMID- 24444262
TI  - Comparing survival and recurrence in curative stage I to III colorectal cancer in
      transfused and nontransfused patients.
AB  - Evidence of the association between blood transfusions and its impact on
      prognostic outcomes in patients who undergo curative resection of colorectal
      cancer remains controversial. The aim of this study was to determine whether
      receiving peri-operative blood transfusions during curative colorectal cancer
      resection affected overall survival, cancer-related survival, and cancer
      recurrence. This retrospective study was undertaken at The Royal Brisbane and
      Women's Hospital, Australia, between 1984 and 2004. The outcomes of 1370 patients
      undergoing curative colorectal cancer resection for TNM stage I to III were
      analyzed. Four hundred twenty three patients (30.9%) required transfusion and 947
      patients (69.1%) did not. Peri-operative transfusion was associated with higher
      rates of cancer recurrence on multivariate analysis (P = 0.024, RR, 1.257, 95%
      CI, 1.03-1.53); however, it was not independently associated with poorer overall
      or cancer-related survival. Where the aim is curative resection, this study
      contributes to a body of evidence that blood transfusions may be associated with
      poorer outcomes.

PMID- 24444263
TI  - Safe transanal tumor resection using a harmonic scalpel.
AB  - We performed a safe and simple transanal tumor resection involving total layer
      resection using a harmonic scalpel as a resecting device. Here we report the
      results of our experience with this technique between 2005 and 2011. This study
      involved 32 patients who underwent transanal tumor resection using a harmonic
      scalpel. The subjects comprised 18 men and 14 women ranging in age from 34 to 87
      years (mean: 64.5 years). The tumors measured 8 to 70 mm (mean: 31 mm) in
      diameter. The operation took 7 to 86 minutes (mean: 29 minutes), and the amount
      of bleeding was 0 to 165 mL (mean: 16.2 mL). There was no intraoperative blood
      loss that necessitated hemostatic procedures. Histopathologically, the lesions
      included hyperplastic polyp in 1 case, adenoma in 9, carcinoma in situ in 7,
      submucosal invasive cancer in 6, muscularis propria cancer in 4, carcinoid in 1,
      malignant lymphoma in 1, gastrointestinal stromal tumor in 1, mucosal prolapsed
      syndrome in 1, and mucosa-associated lymphoid tissue lymphoma in 1. With our
      technique, en bloc resection was achieved in all patients, and the use of a
      harmonic scalpel enabled us to complete the operation within 30 minutes, on
      average, without intraoperative bleeding.

PMID- 24444264
TI  - Seminal vesicle-rectal fistula secondary to anastomotic leakage after low
      anterior resection for rectal cancer: a case report and brief literature review.
AB  - We report a case of a patient with seminal vesicle-rectal fistula, an extremely
      rare complication of low anterior resection of the rectum. A 53-year-old man with
      rectal adenocarcinoma underwent low anterior resection in our hospital. The
      patient experienced diarrhea, pneumaturia, and low-grade fever on postoperative
      day 13. A computed tomography scan showed emphysema in the right seminal vesicle.
      We concluded that anastomotic leakage induced a seminal vesicle-rectal fistula.
      The patient underwent conservative therapy with total parenteral nutrition and
      oral intake of metronidazole. Diarrhea and pneumaturia rapidly improved after
      metronidazole administration and the patient was successfully cured without
      invasive therapy such as colostomy or surgical drainage. A seminal vesicle-rectal
      fistula is a rare complication of low anterior resection, and therapeutic
      strategies for this condition remain elusive. Our report provides valuable
      information on the successful conservative treatment of a secondary seminal
      vesicle-rectal fistula that developed after low anterior resection of the rectum
      in a patient.

PMID- 24444265
TI  - Retrospective review of pilonidal sinus patients with early discharge after
      Limberg flap procedure.
AB  - The aim of this study was to evaluate the results of cases with pilonidal sinus
      (PS) disease that underwent Limberg flap (LF) transposition and to compare the
      short and long-term results of early discharge cases with those in the
      literature. A total of 345 patients who underwent rhomboid excision and LF
      transposition for PS were evaluated retrospectively. No major anesthetic or
      surgical complications occurred. Partial wound dehiscence, localized flap
      necrosis, hematoma, wound infection, and seroma rates were determined as 4.0,
      2.1, 1.5, 3.3, and 3.7% respectively. All patients other than those with a
      hematoma or localized necrosis were discharged with a drain in place 24 hours
      after the operation. The recurrence rate was 3.9% after a mean 33.1-month follow
      up (range, 6-72 months). As a result, we found that short and long-term results
      of patients who underwent LF and were discharged 24 hours after the operation
      were similar to those in the literature. We suggest that patients without
      postoperative complications, such as hematoma or flap necrosis, can be discharged
      early.

PMID- 24444266
TI  - Measures for preventing wound infections during elective open surgery for
      colorectal cancer: scrubbing with gauze.
AB  - In addition to the general surgical-site infection prevention measures in
      colorectal cancer surgery, we performed a simple subcutaneous scrubbing procedure
      with gauze at the time of abdominal closure, which reduced the incidence of wound
      infections. There are 289 patients whose primary colon cancer lesions were
      removed by elective surgeries. They were divided into Group A (74 patients with
      no wound infection prevention measures who were treated from 2002 to 2003), Group
      B (76 patients with wound infection prevention measures who were treated from
      2007 to 2008), and Group C (139 patients with subcutaneous scrubbing with gauze
      plus the measures in Group B who were treated from 2009 to 2012). The incidence
      in Group A was 23%, while the corresponding values in Group B and Group C were
      14.5% and 2.9%, respectively. The incidence of wound infections was substantially
      reduced by additional subcutaneous scrubbing with a saline solution and gauze
      during closure of a surgical incision. This very simple procedure was considered
      useful for surgical site infection prevention.

PMID- 24444267
TI  - Mixed adenoneuroendocrine carcinoma of the colon progressed rapidly after hepatic
      rupture: report of a case.
AB  - The rupture of a metastatic mixed adenoneuroendocrine carcinoma (MANEC) has not
      been previously reported, although the neuroendocrine cell carcinoma is often
      associated with a high incidence of hepatic metastases. The patient was a 39-year
      old male who presented with upper abdominal pain over 3 months. Computed
      tomography showed multiple tumors in both hepatic lobes, while lower
      gastrointestinal endoscopy revealed a tumor in the transverse colon.
      Histopathologic examination of the tumor revealed it to be a neuroendocrine cell
      carcinoma. After the resection of the primary tumor, hepatic metastases rapidly
      increased, and one of them in the left lateral segment was ruptured with
      significant hemorrhage. The rupture led us to undertake the emergency operation
      to stop the bleeding. Histology showed a high-grade large-cell neuroendocrine
      carcinoma associated with moderately differentiated tubular adenocarcinoma. The
      Ki-67 labeling index was 80% (G3). The diagnosis was mixed adenoneuroendocrine
      carcinoma according to the 2010 World Health Organization guidelines. Hepatic
      arterial infusion chemotherapy, systemic chemotherapy, and transcatheter arterial
      chemoembolization did not decrease the tumor progress, and the patient died on
      postoperative day 110. Reporting this highly malignant case, I hope all doctors
      can be interested in MANEC.

PMID- 24444268
TI  - A rare case of granular cell tumor of the anal region: diagnostic difficulty to
      masses in the anal area.
AB  - Granular cell tumor may be located anywhere in the body; however, the
      gastrointestinal tract is infrequently involved and anal granular cell tumors are
      extremely rare. We report herein a rare case of granular cell tumor in the anal
      region. In the current case, a 66-year-old Japanese woman was found to have a
      polypoid lesion in the anus with hemorrhoids. The mass detected as an anal
      polypoid lesion with ulceration was resected and diagnosed as granular cell tumor
      by histologic examination. Granular cell tumor of the anal region is rare, and
      benign perianal polypoid lesions are relatively uncommon clinical findings. They
      might present diagnostic challenges to surgeons and pathologists. Awareness of
      the differential diagnosis of granular cell tumor and careful microscopic
      examination might allow proper management and diagnosis.

PMID- 24444269
TI  - Retroperitoneal liposarcoma with leiomyosarcomatous differentiation.
AB  - We herein describe a 60-year-old Japanese man with a giant retroperitoneal
      liposarcoma undergoing leiomyosarcomatous differentiation. He was admitted to our
      hospital because of a 5-month history of dysphagia and abdominal distention.
      Abdominal computed tomography showed a giant tumor that occupied the entire
      retroperitoneal space. The majority of the mass was lipomatous and low density;
      both a heterogenous and solid mass were also present. A giant retroperitoneal
      liposarcoma was diagnosed, and tumor resection was performed. At surgery, the
      tumor was mostly isolated from the retroperitoneum and other organs.
      Histopathologically, the tumor comprised well-differentiated and dedifferentiated
      liposarcoma with heterologous differentiation of the leiomyosarcomatous
      components, which is a rare phenomenon in liposarcoma. The patient was alive 3
      years after the first treatment, although he has had 3 local recurrences
      (approximately one recurrence yearly) and has been treated by repeated resection
      and radiotherapy.

PMID- 24444270
TI  - Metachronous multiple primary malignant neoplasms of the stomach and the breast:
      report of two cases with review of literature.
AB  - Multiple primary malignant neoplasm is the occurrence of a second primary
      malignancy in the same patient within 6 months of the detection of first primary
      (synchronous), or 6 months or more after primary detection (metachronous).
      Multiple primary malignant neoplasms are not very frequently encountered in
      clinical practice. The relative risk for a second primary malignancy increases by
      1.111-fold every month from the detection of the first primary malignancy in any
      individual. We present 2 patients treated for carcinoma of the breast who
      developed a metachronous primary malignancy in the stomach to highlight the rare
      occurrence of multiple primary malignant neoplasms. These tumors were
      histologically dissimilar, with distinct immunohistochemical parameters. The
      importance lies in carefully identifying the second primary malignancies, not
      dismissing them as metastases, and treating them accordingly.

PMID- 24444271
TI  - Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a
      prospective, randomized study.
AB  - We aimed to compare the clinical outcome and cost of early versus delayed
      laparoscopic cholecystectomy for acute cholecystitis. Sixty patients with acute
      cholecystitis were randomized into early (within 24 hours of admission) or
      delayed (after 6-8 weeks of conservative treatment) laparoscopic cholecystectomy
      groups. There was no significant difference between study groups in terms of
      operation time and rates for conversion to open cholecystectomy. On the other
      hand, total hospital stay was longer (5.2 +/- 1.40 versus 7.8 +/- 1.65 days; P =
      0.04) and total costs were higher (2500.97 +/- 755.265 versus 3713.47 +/- 517.331
      Turkish Lira; P = 0.03) in the delayed laparoscopic cholecystectomy group.
      Intraoperative and postoperative complications were recorded in 8 patients in the
      early laparoscopic cholecystectomy group, whereas no complications occurred in
      the delayed laparoscopic cholecystectomy group (P = 0.002). Despite
      intraoperative and postoperative complications being associated more with early
      laparoscopic cholecystectomy compared with delayed intervention, early
      laparoscopic cholecystectomy should be preferred for treatment of acute
      cholecystitis because of its advantages of shorter hospital stay and lower cost.

PMID- 24444272
TI  - Peripancreatic soft tissue involvement: independent outcome predictor in patients
      with resected pancreatic adenocarcinoma.
AB  - The impact of cancer involving the peripancreatic soft tissue (PST), irrespective
      of margin status, following a resection of pancreatic adenocarcinoma is not
      known. The purpose of this study is to determine such an impact on a cohort of
      patients. Data from 274 patients who underwent pancreatic surgery by our team
      between 1998 and 2012 was reviewed. Of those 119 patients who had pancreatic
      resection for adenocarcinoma were retrospectively analyzed. Patients were
      categorized into 3 groups: Group 1 = R1 resection (N = 39), Group 2 = R0 with
      involved PST (N = 54), and Group 3 = R0 with uninvolved PST (N = 26).
      Demographics, operative data, tumor characteristics and overall survival (OS)
      were evaluated. Operations performed were: Whipple (N = 53), pylorus sparing
      Whipple (N = 41), total pancreatectomy (N = 11), and other (N = 14). Median OS
      for Groups 1, 2, and 3 were 8.5 months, 12 months, and 69.6 months respectively
      (P < 0.001). Tumor size (P = 0.016), margin status (P = 0.006), grade (P =
      0.001), stage (P = 0.037), PST status (P < 0.001), complications (P = 0.046),
      transfusion history (P = 0.003) were all predictors of survival. Cox regression
      analysis demonstrated that grade (HR = 3.1), PST involvement (HR = 2.7),
      transfusion requirement (HR = 2.6) and margin status (HR = 2.0) were the only
      independent predictors of mortality. PST is a novel predictor of poor outcome for
      patients with resected pancreatic cancer.

PMID- 24444273
TI  - Pancreaticoduodenectomy in patients with a history of total gastrectomy for
      stomach cancers.

PMID- 24444274
TI  - Duplicated gallbladder.
AB  - Duplication of the gallbladder is a rare congenital anomaly of the biliary system
      with the incidence of 1 in 3800. A 38-year-old woman visited our patient clinic
      for evaluation of wall thickening of the gallbladder, detected by abdominal
      ultrasonography during a regular medical checkup. Drip infusion
      cholecystocholangiography-computed tomography revealed Y-shaped duplicated
      gallbladders.

PMID- 24444275
TI  - Laparoscopy-assisted total gastrectomy: a simplified approach.
AB  - Laparoscopy-assisted total gastrectomy (LATG), esophagojejunostomy is an
      effective but difficult procedure to perform. We describe a simple modification
      that substantially facilitates insertion of the anvil into the esophagus and
      avoids oral injuries and complications. After mobilization of the stomach and
      esophagus, a semicircumferential esophagotomy is made at the anterior esophageal
      wall. An OrVil anvil (Orvil, Covidien, Norwalk, CT, USA) is delivered
      laparoscopically and secured with a POLYSORB (Covidien) suture to the esophagus.
      The suture is advanced anteriorly so that the center rod penetrates the
      esophageal wall. The esophagus is transected with the stapler at this point. A
      circular-stapled esophagojejunostomy is then performed using the hemidouble
      stapling technique. Laparoscopy-assisted total gastrectomies were performed for
      40 patients with gastric cancers (T1N0M0). All procedures were completed
      laparoscopically without any complications. The time required to place the anvil
      averaged 5 min compared with 9 min reported by others. There were no major
      complications or mortality in this series. The major advantage of this technique
      is that circular stapling is much easier than linear stapling, allowing surgeons
      without advanced surgical skills in LATG to perform the procedure effectively and
      safely.

PMID- 24444276
TI  - Gastric metastasis from renal cell carcinoma with gastrointestinal bleeding: a
      case report and review of the literature.
AB  - A 61-year-old man presented to our hospital with hypercalcemia and elevated C
      reactive protein (CRP). Evaluation revealed renal cell carcinoma (RCC) with
      metastasis to lung, bone, and brain. He underwent partial resection of the right
      kidney and a left nephrectomy. Histopathologic findings of resected tumors were
      consistent with clear cell RCC. Whole-brain irradiation was performed for
      management of brain metastasis. Postoperatively, he was treated with molecularly
      targeted therapy using a mammalian target of rapamycin inhibitor. Approximately
      14 months later, he suffered an episode of upper gastrointestinal bleeding with
      secondary anemia and melena. Upper gastrointestinal endoscopy revealed a
      distinctly protruding lesion in the gastric body. Biopsy of the gastric lesion
      showed metastatic clear cell RCC. He underwent partial gastrectomy. His
      postoperative course was uneventful. However, 4 months after surgery, he died
      from brain metastasis. Metastatic RCC to the stomach, although rare, should be
      suspected in any patient with a history of RCC who presents with gastrointestinal
      symptoms.

PMID- 24444277
TI  - Portal vein stenting to treat portal vein stenosis in a patient with malignant
      tumor and gastrointestinal bleeding.
AB  - This report describes the successful use of portal venous stent placement for a
      patient with recurrent melena secondary to jejunal varices that developed after
      subtotal stomach preserved pancreatoduodenectomy (SSPPD). A 67-year-old man was
      admitted to our hospital with tarry stool and severe anemia at 2 years after
      SSPPD for carcinoma of the head of the pancreas. Abdominal computed tomography
      examination showed severe stenosis of the extrahepatic portal vein caused by
      local recurrence and showed an intensely enhanced jejunal wall at the
      choledochojejunostomy. Gastrointestinal bleeding scintigraphy also revealed
      active bleeding near the choledochojejunostomy. Based on these findings, jejunal
      varices resulting from portal vein stenosis were suspected as the cause of the
      melena. Portal vein stenting and balloon dilation was performed via the ileocecal
      vein after laparotomy. Coiling of the jejunal varices and sclerotherapy of the
      dilate postgastric vein with 5% ethanolamine oleate with iopamidol was performed.
      After portal stent placement, the patient was able to lead a normal life without
      gastrointestinal hemorrhage. However, he died 7 months later due to liver
      metastasis.

PMID- 24444278
TI  - Mechanical stimulation of the left ventricle as a temporizing life sustaining
      maneuver.

PMID- 24444279
TI  - A model system to study the lignification process in Eucalyptus globulus.
AB  - Recalcitrance of plant biomass is closely related to the presence of the phenolic
      heteropolymer lignin in secondary cell walls, which has a negative effect on
      forage digestibility, biomass-to-biofuels conversion and chemical pulping. The
      genus Eucalyptus is the main source of wood for pulp and paper industry. However,
      when compared to model plants such as Arabidopsis thaliana and poplar, relatively
      little is known about lignin biosynthesis in Eucalyptus and only a few genes were
      functionally characterized. An efficient, fast and inexpensive in vitro system
      was developed to study lignification in Eucalyptus globulus and to evaluate the
      potential role of candidate genes in this biological process. Seedlings were
      grown in four different conditions, in the presence or absence of light and with
      or without sucrose in the growth medium, and several aspects of lignin metabolism
      were evaluated. Our results showed that light and, to a lesser extent, sucrose
      induced lignin biosynthesis, which was followed by changes in S/G ratio, lignin
      oligomers accumulation and gene expression. In addition, higher total peroxidase
      activity and differential isoperoxidase profile were observed when seedlings were
      grown in the presence of light and sucrose. Peptide sequencing allowed the
      identification of differentially expressed peroxidases, which can be considered
      potential candidate class III peroxidases involved in lignin polymerization in E.
      globulus. 

PMID- 24444280
TI  - The effect of desmopressin on bleeding time and platelet aggregation in healthy
      volunteers administered ticagrelor.
AB  - WHAT IS KNOWN AND OBJECTIVE: Ticagrelor is a reversibly binding and selective
      P2Y12 -receptor antagonist approved for the prevention of atherothrombotic events
      in patients with acute coronary syndromes. As bleeding events remain a hazard
      with antiplatelet therapy, this study investigated the effect of the vasopressin
      agonist, desmopressin, on ticagrelor-induced bleeding time prolongation.
      Desmopressin has previously been shown to improve primary haemostasis and is
      widely used as first-line therapy for individuals with bleeding disorders.
      METHODS: In a randomized, double-blind, 2-period crossover study, healthy
      volunteers received ticagrelor (270 mg loading dose; 180 mg bid) for 5 days. On
      Day 5, desmopressin (0.3 MUg/kg) or saline intravenous infusions were
      administered. The impact of desmopressin on bleeding time, inhibition of platelet
      aggregation (IPA), platelet function and ticagrelor pharmacokinetic parameters
      was investigated. RESULTS: Twenty-one volunteers (81% male) were enrolled. Median
      [range] bleeding times were slightly reduced with ticagrelor plus desmopressin
      compared with ticagrelor alone (7.50 [3-17] vs. 10.50 [3-25] min at 2.5 h).
      Median reductions in bleeding time from baseline were generally similar between
      ticagrelor plus desmopressin compared with ticagrelor alone at all time points.
      Co-administration of desmopressin had no impact on IPA, although platelet
      reactivity was significantly increased (von Willebrand Factor antigen: GLS mean
      AUEC was 4667%.h for ticagrelor plus desmopressin compared with 2750%.h for
      ticagrelor alone). Desmopressin did not influence the pharmacokinetics of
      ticagrelor. WHAT IS NEW AND CONCLUSION: Desmopressin had no significant effect on
      bleeding time or inhibition of platelet aggregation by ticagrelor, although
      primary haemostatic activity was significantly increased. Ticagrelor
      pharmacokinetic parameters were not affected by co-administration with
      desmopressin. Therefore, desmopressin is unlikely to be an effective therapeutic
      agent for control of the potential bleeding events associated with ticagrelor.

PMID- 24444281
TI  - Sonoelastography of the lower uterine segment and cervix.

PMID- 24444282
TI  - Flood of fear.

PMID- 24444283
TI  - Incidence, indications, and predictors of adverse outcomes of postpartum
      hysterectomies: 20-year experience in a tertiary care centre.
AB  - OBJECTIVE: Postpartum hysterectomy is an uncommon yet serious obstetric procedure
      associated with maternal morbidity and mortality. The objectives of our study
      were to assess the incidence of and indications for PH and to identify predictors
      of massive hemorrhage and coagulopathy. METHODS: We conducted a retrospective
      cohort study on all cases of PH performed at the Jewish General Hospital, McGill
      University, between 1992 and 2011. Data were collected from individual patient
      charts and logistics regression models were used to evaluate predictors of
      adverse events. RESULTS: Over a 20-year study period, there were 76 938 live
      births and 67 postpartum hysterectomies for an overall incidence of 0.87/1000.
      Although overall PH rates increased over time predominantly because of increasing
      rates of planned PH for placental abnormalities, there was a decrease in
      unplanned emergency postpartum hysterectomies. The main indications for PH were
      abnormal placentation (64.2%) and postpartum hemorrhage (26.9%). In adjusted
      analysis, the risk of requiring massive blood transfusion was increased when PH
      was performed after vaginal delivery or Caesarean section (OR 102.1; 95% CI 4.22
      to 2468) and in association with postpartum hemorrhage (OR 9.1; 95% CI 1.3 to
      64.3). The risk of massive hemorrhage was lower if occlusive balloons were placed
      antenatally in the uterine arteries (OR 0.13; 95% CI 0.03 to 0.68) and if PH was
      performed by a dedicated experienced surgeon (OR 0.23; 95% CI 0.06 to 0.86).
      CONCLUSION: Although overall rates of PH are increasing, antenatal recognition of
      placental pathologies have resulted in fewer postpartum hysterectomies being done
      as emergencies. The use of occlusive balloons in the uterine arteries and having
      the procedure performed by a dedicated surgeon skilled in performing postpartum
      hysterectomy can reduce overall serious morbidity.

PMID- 24444284
TI  - Temporal trends in postpartum hemorrhage and severe postpartum hemorrhage in
      Canada from 2003 to 2010.
AB  - OBJECTIVE: Increases in postpartum hemorrhage have been reported from several
      countries. We assessed temporal trends in postpartum hemorrhage and severe
      postpartum hemorrhage in Canada between 2003 and 2010. METHODS: We carried out a
      population-based cohort study of all hospital deliveries in Canada (excluding
      Quebec) from 2003 to 2010 (n = 2 193 425), using data from the Canadian Institute
      for Health Information. Postpartum hemorrhage was defined as a blood loss of >=
      500 mL following vaginal delivery or >= 1000 mL following Caesarean section, or
      as noted by the care provider. Severe postpartum hemorrhage was defined as
      postpartum hemorrhage plus blood transfusion, hysterectomy, or other procedures
      to control bleeding (including uterine suturing or ligation/embolization of
      pelvic arteries). Temporal trends were assessed using the chi-square test for
      trend, relative risks, and logistic regression. RESULTS: Postpartum hemorrhage
      increased by 22% (95% CI 20% to 25%) from 5.1% in 2003 to 6.2% in 2010 (P <
      0.001), driven by a 29% increase (95% CI 26% to 33%) in atonic postpartum
      hemorrhage (3.9% in 2003 vs. 5.0% in 2010, P < 0.001). Postpartum hemorrhage with
      blood transfusion increased from 36.7 to 50.4 per 10 000 deliveries (P < 0.001),
      while postpartum hemorrhage with hysterectomy increased from 4.9 to 5.8 per 10
      000 deliveries (P < 0.01). Postpartum hemorrhage with uterine suturing, or
      ligation/embolization of pelvic arteries, increased from 4.1 to 10.7 per 10 000
      deliveries (P < 0.001). These increases occurred in most provinces and
      territories, and could not be explained by changes in maternal, fetal, and
      obstetric factors. CONCLUSION: Rates of postpartum hemorrhage and severe
      postpartum hemorrhage continued to increase in Canada between 2003 and 2010.

PMID- 24444285
TI  - Pregnancy and maternal outcomes in women with prior or current gastrointestinal
      malignancies.
AB  - OBJECTIVES: To review the fetal and maternal outcomes of women with a diagnosis
      of gastrointestinal (GI) cancer before or during pregnancy. METHODS: We conducted
      a retrospective cohort study of pregnant women referred to a single tertiary care
      centre with a current or previous diagnosis of GI malignancy. Maternal,
      obstetric, and infant data were recorded. RESULTS: We identified 18 pregnancies
      in 13 women. Nine women were found to have a GI malignancy during pregnancy
      (group 1). There was an indirect maternal death in this group in a woman with
      advanced gastric adenocarcinoma. Nine unique pregnancies occurred in eight women
      with diagnosis and management of GI malignancies before their pregnancies (group
      2). CONCLUSION: GI malignancies are difficult to diagnose and manage during
      pregnancy and are usually advanced at the time of diagnosis. Surgery can be
      performed during pregnancy if necessary, with chemotherapy and radiotherapy
      usually deferred to the postpartum period. Women who have had a prior GI
      malignancy have special circumstances related to the type of surgery performed
      and previous exposure to chemotherapy. These patients may benefit from a
      multidisciplinary team effort to optimize their care.

PMID- 24444286
TI  - Universal vaginal applicator for the uniform distribution of vaginal gel and
      cream formulations: a magnetic resonance imaging study.
AB  - OBJECTIVE: Conventional vaginal applicators with a single apical hole do not
      distribute vaginal formulations homogenously and do not cover the entire vaginal
      and cervical mucosa. To overcome this problem and offer women further protection
      against vaginal infections, we designed a unique vaginal applicator with multiple
      apical and lateral holes. We have previously shown that the new applicator
      distributes an investigational vaginal gel homogenously over the entire vaginal
      and cervical mucosa. In this study, we investigated (using MRI) whether the new
      applicator works as well with marketed vaginal gels and creams. METHODS: Eighteen
      women participated in the study and six vaginal gels and creams were tested. Each
      woman used a marketed vaginal product with its own commercial applicator (CA)
      once and with our universal vaginal applicator (UVA) once to deliver the same
      product. The applications were separated by a one-week period. Pelvic MRI was
      performed immediately after vaginal application to evaluate the product's
      distribution and mucosal coverage. RESULTS: Immediately after application of the
      vaginal product, the UVA homogenously distributed the six products (3 gels and 3
      creams) over the entire vaginal and cervical mucosa. On the other hand, the
      tested CA delivered four products (3 gels and 1 cream) mainly to the cervix and
      the upper vagina, but not to the mid and lower vagina; for the other two creams,
      the distribution was similar to that of UVA. Furthermore, the UVA received the
      highest acceptability score. CONCLUSION: The UVA can be used to deliver different
      vaginal gel and cream products homogenously throughout the vagina. This was the
      first time the UVA had been tested with marketed vaginal gels and creams. This
      applicator, giving uniform mucosal coverage and being highly acceptable, may help
      women to better protect themselves against sexually transmitted infections.

PMID- 24444287
TI  - What proportion of Canadian women will accept an intrauterine contraceptive at
      the time of second trimester abortion? Baseline data from a randomized controlled
      trial.
AB  - OBJECTIVE: This report details enrolment findings related to a Canadian
      randomized controlled trial comparing immediate to delayed intrauterine
      contraception (IUC) placement after a second trimester abortion. We report
      acceptance of IUC, satisfaction with prior contraception, adherence to the
      CONSORT criteria, and challenges faced in the recruitment process. METHODS: Women
      seeking second trimester abortion and selecting either of two methods of IUC as
      their preferred contraception method were enrolled and randomized to insertion
      either immediately post-abortion or four weeks later. Enrolled participants
      completed a Contraception Satisfaction Questionnaire detailing prior
      contraceptive satisfaction. RESULTS: Among 1813 women assessed, 1500 (83%) met
      eligibility criteria and IUC was chosen for post-abortion contraception by over
      one half of them (792/1500, 53%). When both types of device were available cost
      free, women selected the levonorgestrel-releasing intrauterine system more than
      20 times more frequently than a copper IUD. Participants had an average age of
      26.0 (standard deviation [SD] 6.8) years, and an average gestational age of 16.1
      (SD 3.1) weeks. Almost one half (48.4%) had had a prior abortion and 46.9% had a
      prior delivery. Two thirds of participants were using a contraception method at
      the time of conception, but almost one third of these were using methods in the
      lowest tiers of effectiveness. There was a weak correlation between prior
      contraceptive compliance and education level. CONCLUSION: More than one half of
      eligible women seeking a second-trimester abortion chose IUC for post-abortion
      contraception. In Canada, health care for unintended pregnancies is universally
      subsidized but contraception is not. Offering comprehensive information on the
      range of contraceptive methods and providing cost-free IUC is an effective
      strategy to increase uptake of intrauterine contraception among Canadian women
      who wish to prevent further unintended pregnancy.

PMID- 24444288
TI  - Fetal pharmacotherapy 4: fetal thyroid disorders.

PMID- 24444289
TI  - Pregnancy outcomes after assisted human reproduction.
AB  - OBJECTIVE: To review the effect of assisted human reproduction (AHR) on perinatal
      outcomes, to identify areas requiring further research with regard to birth
      outcomes and AHR, and to provide guidelines to optimize obstetrical management
      and counselling of prospective Canadian parents. OUTCOMES: This document compares
      perinatal outcomes of different types of AHR pregnancies with each other and with
      those of spontaneously conceived pregnancies. Clinicians will be better informed
      about the adverse outcomes that have been documented in association with AHR,
      including obstetrical complications, adverse perinatal outcomes, multiple
      gestations, structural congenital abnormalities, chromosomal abnormalities, and
      imprinting disorders. EVIDENCE: Published literature was retrieved through
      searches of MEDLINE and the Cochrane Library from January 2005 to December 2012
      using appropriate controlled vocabulary and key words (assisted reproduction,
      assisted reproductive technology, ovulation induction, intracytoplasmic sperm
      injection, embryo transfer, and in vitro fertilization). Results were not
      restricted to systematic reviews, randomized control trials/controlled clinical
      trials, and observational studies; studies of all designs published in English
      from January 2005 to December 2012 were reviewed, and additional publications
      were identified from the bibliographies of these articles. Searches were updated
      on a regular basis and incorporated in the guideline to August 2013. Grey
      (unpublished) literature was identified through searching the websites of health
      technology assessment and health technology assessment-related agencies, clinical
      practice guideline collections, clinical trial registries, and national and
      international medical specialty societies. VALUES: The quality of evidence in
      this document was rated using the criteria described in the Report of the
      Canadian Task Force on Preventive Health Care (Table 1). Summary Statements 1.
      There is increasing evidence that infertility or subfertility is an independent
      risk factor for obstetrical complications and adverse perinatal outcomes, even
      without the addition of assisted human reproduction. (II-2) 2. The relative risk
      for an imprinting phenotype such as Silver-Russell syndrome, Beckwith-Wiedemann
      syndrome, or Angelman syndrome is increased in the assisted reproduction
      population, but the actual risk for one of these phenotypes to occur in an
      assisted pregnancy is estimated to be low, at less than 1 in 5000. The exact
      biological etiology for this increased imprinting risk is likely heterogeneous
      and requires more research. (II-2) Recommendations 1. All men with severe
      oligozoospermia or azoospermia (sperm count < 5 million/hpf) should be offered
      genetic/clinical counselling, karyotype assessment for chromosomal abnormalities,
      and Y-chromosome microdeletion testing prior to in vitro fertilization with
      intracytoplasmic sperm injection. (II-2A) 2. All men with unexplained obstructive
      azoospermia should be offered genetic/clinical counselling and genetic testing
      for cystic fibrosis prior to in vitro fertilization with intracytoplasmic sperm
      injection. (II-2A) 3. Multiple pregnancy is the most powerful predictive factor
      for adverse maternal, obstetrical, and perinatal outcomes. Couples should be
      thoroughly counselled about the significant risks of multiple pregnancies
      associated with all assisted human reproductive treatments. (II-2A) 4. The
      benefits and cumulative pregnancy rates of elective single embryo transfer
      support a policy of using this protocol in couples with good prognosis for
      success, and elective single embryo transfer should be strongly encouraged in
      this population. (II-2A) 5. To reduce the incidence of multiple pregnancy, health
      care policies that support public funding for assisted human reproduction, with
      regulations promoting best practice regarding elective single embryo transfer,
      should be strongly encouraged. (II-2A) 6. Among singleton pregnancies, assisted
      reproductive technology is associated with increased risks of preterm birth and
      low birth weight infants, and ovulation induction is associated with an increased
      risk of low birth weight infants. Until sufficient research has clarified the
      independent roles of infertility and treatment for infertility, couples should be
      counselled about the risks associated with treatment. (II-2B) There is a role for
      closer obstetric surveillance of women who conceive with assisted human
      reproduction. (III-L) 7. There is growing evidence that pregnancy outcomes are
      better for cryopreserved embryos fertilized in vitro than for fresh embryo
      transfers. This finding supports a policy of elective single embryo transfer for
      women with a good prognosis (with subsequent use of cryopreserved embryos as
      necessary), and may reassure women who are considering in vitro fertilization.
      (II-2A) 8. Women and couples considering assisted human reproduction and
      concerned about perinatal outcomes in singleton pregnancies should be advised
      that (1) intracytoplasmic sperm injection does not appear to confer increased
      adverse perinatal or maternal risk over standard in vitro fertilization, and (2)
      the use of donor oocytes increases successful pregnancy rates in selected women,
      but even when accounting for maternal age, can increase the risks of low birth
      weight and preeclampsia. (II-2B) 9. Any assisted reproductive technology
      procedure should be prefaced by a discussion of fetal outcomes and the slight
      increase in the risk of congenital structural abnormalities, with emphasis on
      known confounding factors such as infertility and body mass index. (II-2B) 10. In
      pregnancies achieved by artificial reproductive technology, routine anatomic
      ultrasound for congenital structural abnormalities is recommended between 18 and
      22 weeks. (II-2A) 11. Pregnancies conceived by intracytoplasmic sperm injection
      may be at increased risk of chromosomal aberrations, including sex chromosome
      abnormalities. Diagnostic testing should be offered after appropriate
      counselling. (II-2A) 12. The possible increased risk for late onset cancer due to
      gene dysregulation for tumour suppression requires more long-term follow-up
      before the true risk can be determined. (III-A) 13. The clinical application of
      preimplantation genetic testing in fertile couples must balance the benefits of
      avoiding disease transmission with the medical risks and financial burden of in
      vitro fertilization. (III-B) 14. Preimplantation screening for aneuploidy is
      associated with inconsistent findings for improving pregnancy outcomes. Any
      discussion of preimplantation genetic screening with patients should clarify that
      there is no adequate information on the long-term effect of embryo single cell
      biopsy. (I-C).

PMID- 24444292
TI  - Acupuncture therapy: mechanism of action, efficacy, and safety: a potential
      intervention for psychogenic disorders?
AB  - Scientific bases for the mechanism of action of acupuncture in the treatment of
      pain and the pathogenic mechanism of acupuncture points are briefly summarized.
      The efficacy and safety of acupuncture therapy is discussed based on the results
      of German clinical trials. A conclusion on the role for acupuncture in the
      treatment of psychogenic disorders could not be reached. 

PMID- 24444291
TI  - Biochemical and genetic characterization of Trypanosoma cruzi N
      myristoyltransferase.
AB  - Co- and post-translational N-myristoylation is known to play a role in the
      correct subcellular localization of specific proteins in eukaryotes. The enzyme
      that catalyses this reaction, NMT (N-myristoyltransferase), has been
      pharmacologically validated as a drug target in the African trypanosome,
      Trypanosoma brucei. In the present study, we evaluate NMT as a potential drug
      target in Trypanosoma cruzi, the causative agent of Chagas' disease, using
      chemical and genetic approaches. Replacement of both allelic copies of TcNMT (T.
      cruzi NMT) was only possible in the presence of a constitutively expressed
      ectopic copy of the gene, indicating that this gene is essential for survival of
      T. cruzi epimastigotes. The pyrazole sulphonamide NMT inhibitor DDD85646 is 13-23
      fold less potent against recombinant TcNMT than TbNMT (T. brucei NMT), with Ki
      values of 12.7 and 22.8 nM respectively, by scintillation proximity or coupled
      assay methods. DDD85646 also inhibits growth of T. cruzi epimastigotes (EC50=6.9
      MUM), but is ~1000-fold less potent than that reported for T. brucei. On-target
      activity is demonstrated by shifts in cell potency in lines that over- and under
      express NMT and by inhibition of intracellular N-myristoylation of several
      proteins in a dose-dependent manner. Collectively, our findings suggest that N
      myristoylation is an essential and druggable target in T. cruzi. 

PMID- 24444294
TI  - A new many-body potential energy surface for HCl clusters and its application to
      anharmonic spectroscopy and vibration-vibration energy transfer in the HCl
      trimer.
AB  - The hydrogen bond has been studied by chemists for nearly a century. Interest in
      this ubiquitous bond has led to several prototypical systems emerging to studying
      its behavior. Hydrogen chloride clusters stand as one such example. We present
      here a new many-body potential energy surface for (HCl)n constructed from one-,
      two-, and three-body interactions. The surface is constructed from previous
      highly accurate, semiempirical monomer and dimer surfaces, and a new high-level
      ab initio permutationally invariant full-dimensional three-body potential. The
      new three-body potential is based on fitting roughly 52,000 three-body energies
      computed using coupled cluster with single, doubles, perturbative triples, and
      explicit correlation and the augmented correlation consistent double-zeta basis
      set. The first application, described here, is to the ring HCl trimer, for which
      the many-body representation is exact. The new potential describes all known
      stationary points of the trimer as well its dissociation to either three monomers
      or a monomer and a dimer. The anharmonic vibrational energies are computed for
      the three H-Cl stretches, using explicit three-mode coupling calculations and
      local-monomer calculations with Huckel-type coupling. Both methods produce
      frequencies within 5 cm(-1) of experiment. A wavepacket calculation based on the
      Huckel model and full-dimensional classical calculation are performed to study
      the monomer H-Cl stretch vibration-vibration transfer process in the ring HCl
      trimer. Somewhat surprisingly, the results of the quantum and classical
      calculations are virtually identical, both exhibiting coherent beating of the
      excitation between the three monomers. Finally, this representation of the
      potential is used to study properties of larger clusters, namely to compute
      optimized geometries of the tetramer, pentamer, and hexamer and to perform
      explicit four-mode coupling calculations of the tetramer's anharmonic stretch
      frequencies. The optimized geometries are found to be in agreement with those of
      previous ab initio studies and the tetramer's anharmonic frequencies are computed
      within 11 cm(-1) of experiment.

PMID- 24444293
TI  - Screening models using multiple markers for early detection of late-onset
      preeclampsia in low-risk pregnancy.
AB  - BACKGROUND: Our primary objective was to establish a cutoff value for the soluble
      fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured
      using the Elecsys assay to predict late-onset preeclampsia in low-risk
      pregnancies. Our secondary objective was to evaluate the ability of combination
      models using Elecsys data, second trimester uterine artery (UtA) Doppler
      ultrasonography measurements, and the serum fetoplacental protein levels used for
      Down's syndrome screening, to predict preeclampsia. METHODS: This prospective
      cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma
      levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of
      alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and
      inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women
      underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation. RESULTS:
      Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver
      operating characteristic curve analysis showed that the third trimester sFlt
      1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed
      false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF
      ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used
      to determine the five best combination models for early detection of late-onset
      preeclampsia. The combination of the PAPP-A level and the second trimester sFlt
      1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of
      second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed
      FPR of 10%, the combination of body mass index and the second trimester sFlt-1
      level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A
      and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the
      combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded
      a DR of 62.5% at a fixed FPR of 10%. CONCLUSIONS: The combination of the PAPP-A
      level and the second trimester sFlt-1/PlGF ratio, and the combination of the
      second trimester sFlt-1 level with body mass index, were better predictors of
      late-onset preeclampsia than any individual marker.

PMID- 24444295
TI  - Gene-environment interaction in atopic diseases: a population-based twin study of
      early-life exposures.
AB  - INTRODUCTION: The development of atopic diseases early in life suggests an
      important role of perinatal risk factors. OBJECTIVES: To study whether early-life
      exposures modify the genetic influence on atopic diseases in a twin population.
      METHODS: Questionnaire data on atopic diseases from 850 monozygotic and 2279 like
      sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were
      cross-linked with data on prematurity, Cesarean section, maternal age at birth,
      parental cohabitation, season of birth and maternal smoking during pregnancy,
      from the Danish National Birth Registry. Significant predictors of atopic
      diseases were identified with logistic regression and subsequently tested for
      genetic effect modification using variance components analysis. RESULTS: After
      multivariable adjustment, prematurity (gestational age below 32 weeks) [odds
      ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR =
      1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42
      2.04) significantly influenced the risk of asthma, whereas none of the factors
      were significantly associated with atopic dermatitis and hay fever. Variance
      components analysis stratified by exposure status showed no significant change in
      the heritability of asthma according to the identified risk factors. CONCLUSION:
      In this population-based study of children, there was no evidence of genetic
      effect modification of atopic diseases by several identified early-life risk
      factors. The causal relationship between these risk factors and atopic diseases
      may therefore be mediated via mechanisms different from gene-environment
      interaction.

PMID- 24444296
TI  - Applications of convolution voltammetry in electroanalytical chemistry.
AB  - The robustness of convolution voltammetry for determining accurate values of the
      diffusivity (D), bulk concentration (C(b)), and stoichiometric number of
      electrons (n) has been demonstrated by applying the technique to a series of
      electrode reactions in molecular solvents and room temperature ionic liquids
      (RTILs). In acetonitrile, the relatively minor contribution of nonfaradaic
      current facilitates analysis with macrodisk electrodes, thus moderate scan rates
      can be used without the need to perform background subtraction to quantify the
      diffusivity of iodide [D = 1.75 (+/-0.02) * 10(-5) cm(2) s(-1)] in this solvent.
      In the RTIL 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide,
      background subtraction is necessary at a macrodisk electrode but can be avoided
      at a microdisk electrode, thereby simplifying the analytical procedure and
      allowing the diffusivity of iodide [D = 2.70 (+/-0.03) * 10(-7) cm(2) s(-1)] to
      be quantified. Use of a convolutive procedure which simultaneously allows D and
      nC(b) values to be determined is also demonstrated. Three conditions under which
      a technique of this kind may be applied are explored and are related to
      electroactive species which display slow dissolution kinetics, undergo a single
      multielectron transfer step, or contain multiple noninteracting redox centers
      using ferrocene in an RTIL, 1,4-dinitro-2,3,5,6-tetramethylbenzene, and an
      alkynylruthenium trimer, respectively, as examples. The results highlight the
      advantages of convolution voltammetry over steady-state techniques such as
      rotating disk electrode voltammetry and microdisk electrode voltammetry, as it is
      not restricted by the mode of diffusion (planar or radial), hence removing
      limitations on solvent viscosity, electrode geometry, and voltammetric scan rate.

PMID- 24444297
TI  - Expression of the Escherichia coli ompW colicin S4 receptor gene is regulated by
      temperature and modulated by the H-NS and StpA nucleoid-associated proteins.
AB  - The OmpW family consists of a ubiquitous group of small outer membrane (OM) beta
      barrel proteins of Gram-negative bacteria with proposed roles in environmental
      adaptation but poorly understood mechanisms of expression. We report here that
      Escherichia coli K-12 OmpW contents are drastically modified by temperature
      changes compatible with the leap from the environment to warm-blooded hosts
      and/or vice versa. Thus, while OmpW is present in the OM of bacteria grown at 37 
      degrees C, it sharply disappears at 23  degrees C with the concomitant
      acquisition of colicin S4 resistance by the cells. ompW::lacZY fusions indicated
      that temperature regulation operates at the level of transcription, being ompW
      expression almost abolished at 23  degrees C as compared to 37  degrees C.
      Moreover, E. coli Deltahns mutants lacking H-NS showed reductions in ompW
      transcription and OmpW contents at 37  degrees C, indicating positive modulatory
      roles for this nucleoid-structuring protein in ompW expression. Also,
      DeltahnsDeltastpA double mutants simultaneously lacking H-NS and its paralog StpA
      showed more severe reductions in ompW expression at 37  degrees C, resulting in
      the complete loss of OmpW. The overall results indicate that OmpW contents in E.
      coli are regulated by both temperature and H-NS and reinforce OmpW functions in
      bacterial adaptation to warm-blooded hosts.

PMID- 24444298
TI  - Trauma, depression, and resilience of earthquake/tsunami/nuclear disaster
      survivors of Hirono, Fukushima, Japan.
AB  - AIM: A mega-earthquake and tsunami struck the northeastern coast of Japan, and
      many survivors were forced to evacuate to temporary housing due to rising
      radiation levels. The aims of this study were to investigate the prevalence of
      symptoms of post-traumatic stress disorder (PTSD), depression, and poor general
      health among survivors, to test the predictive roles of resilience on mental and
      physical health, and to examine the predictive sociodemographic factors on
      resilience. METHODS: Two hundred and forty-one evacuees (men/women: 116/125) from
      Hirono, Fukushima participated in the study. They were asked to complete the
      Connor-Davidson Resilience Scale, the Zung Self-Rating Depression Scale, the
      Impact of Events Scale-Revised, and a demographic questionnaire. RESULTS: Among
      all participants, 53.5% exhibited the clinically concerning symptoms of PTSD, and
      among them 33.2% indicated clinical PTSD symptoms. Additionally, 66.8% reported
      symptoms of depression, and among them 33.2% showed mildly depressive symptoms,
      while 19.1% and 14.5% demonstrated moderate and severe depressive symptoms,
      respectively. Resilience was a significant buffer for depression, PTSD, and
      general health. Additionally, employment status, eating/exercise habits, and
      drinking habits predicted resilience. CONCLUSION: The results indicated that
      depression and PTSD are prevalent among the survivors of massive earthquakes,
      tsunamis, and accidents from nuclear power plants. However, the results also
      showed that some survivors managed to endure the traumatic events relatively
      well, and resilience was a significant protective factor in dealing with such
      events. Therefore, it is crucial to assist survivors in improving their
      resilience by providing job opportunities and encouraging a healthy lifestyle.

PMID- 24444299
TI  - Exploring schema-driven differences in situation awareness between road users: an
      on-road study of driver, cyclist and motorcyclist situation awareness.
AB  - Collisions between different road users make a substantial contribution to road
      trauma. Although evidence suggests that different road users interpret the same
      road situations differently, it is not clear how road users' situation awareness
      differs, nor is it clear which differences might lead to conflicts. This article
      presents the findings from an on-road study conducted to examine driver,
      motorcyclist and cyclist situation awareness in different road environments. The
      findings suggest that, in addition to minor differences in the structure of
      different road users' situation awareness (i.e. amount of information and how it
      is integrated), the actual content of situation awareness in terms of road user
      schemata, the resulting interaction with the world and the information
      underpinning situation awareness is markedly different. Further examination
      indicates that the differences are likely to be compatible along arterial roads,
      shopping strips and at roundabouts, but that they may create conflicts between
      different road users at intersections. Interventions designed to support
      compatible situation awareness and behaviour between different road users are
      discussed. 

PMID- 24444301
TI  - Acute central hypothyroidism, diabetes insipidus and central hypogonadism in a 36
      year-old woman.

PMID- 24444300
TI  - Deep brain stimulation for dystonia.
AB  - Deep brain stimulation (DBS) is an effective surgical treatment for medication
      refractory movement disorders, and has been approved by the United States Food
      and Drug Administration for treatment of dystonia. The success of DBS in the
      treatment of dystonia depends on our understanding of the anatomy and physiology
      of this disorder and close collaboration between neurosurgeons, neurologists,
      clinical neurophysiologists, neuroradiologists and neuropsychologists. Currently,
      pallidal DBS is an established treatment option for medically refractive
      dystonia. This review is intended to provide a comprehensive review of the use of
      DBS for dystonia, focusing mainly on the surgical aspects, clinical outcome, MRI
      findings and side effects of DBS. 

PMID- 24444302
TI  - Advanced oxidation technology with photohydroionization as a surface treatment
      for controlling Listeria monocytogenes on stainless steel surfaces and ready-to
      eat cheese and turkey.
AB  - Listeria monocytogenes is difficult to control in food and processing
      environments due to its widespread nature and ability to survive in a range of
      adverse conditions, including low temperatures, pH, and high salt concentrations.
      The objective of this study was to evaluate the efficacy of
      PhotohydroionizationTM (PHI; RGF Environmental Group, Inc., Riviera, Beach, FL),
      a novel advanced oxidation technology, as a surface treatment to control L.
      monocytogenes on food-contact surfaces, sliced American cheese, and ready-to-eat
      (RTE) turkey. A five-strain cocktail of L. monocytogenes was used to inoculate
      sample surfaces. Food-contact surfaces were exposed to ultraviolet and other
      oxidative gases produced by the PHI system for 10, 20, 30, 45, 60, and 120 s and
      5, 10, and 15 min; cheese and turkey samples were treated for 30, 60, and 120 s
      and 5 min. For each matrix at each time point, seven samples were treated and
      enumerated by plating appropriate dilutions onto modified oxford medium and thin
      agar-layer modified oxford medium. Results showed reductions (p<0.05) in L.
      monocytogenes: 4.37 log colony-forming units (CFU)/coupon on stainless steel
      after 15-min treatment. A 1.39 and 1.63 log CFU/sample after 120 s and 2.16 and
      2.52 log CFU/sample after 5 min were seen on American cheese and ready-to-eat
      turkey, respectively. Lipid oxidation analyses performed on cheese and turkey
      samples indicated that PHI treatment did not affect (p>0.05) thiobarbituric acid
      reactive substances values. This study demonstrates the efficacy of PHI treatment
      to reduce L. monocytogenes on stainless steel and RTE foods and may serve as a
      processing intervention to ensure safe production of food.

PMID- 24444303
TI  - Functional dental occlusion: an anthropological perspective and implications for
      practice.
AB  - Physiologic changes occur in dental occlusion throughout life, resulting from the
      interplay between functional demands and reciprocating adaptive responses. These
      changes have been reported in the anthropological literature and they reflect
      evolutionary changes in the human stomatognathic system during the Paleolithic,
      hunter-gatherer period. Specific occlusal changes occur in response to different
      environments, leading to extensive variation within and between extinct and
      extant human populations. For example, functional demands can cause occlusal and
      interproximal tooth wear, resulting in shortening of the dental arch, continual
      tooth eruption and changes in masticatory patterns. Since the advent of farming
      through to our current industrialized culture, functional demands on the human
      masticatory system, and its adaptive responses to these demands, have been
      reduced considerably. Indeed, it is only occasionally that functional demands are
      severe enough to lead to obvious pathology in the modern human dentition. In
      contrast to normal masticatory activity, 'modern-day conditions' such as dental
      caries, periodontal disease and erosion, can lead to significant changes in
      dental occlusion that are pathological and need to be treated. The masticatory
      system is a dynamic, functional unit that displays considerable change over a
      lifetime. In this concept paper, it is proposed that modern human populations
      living in industrialized environments display dental occlusions that can be
      considered to be 'neotenous'; that is, our dentitions tend to reflect an unworn
      stage of our ancestors that was only seen in infants, juveniles and young adults.
      Clinicians can draw on both phylogenetic and ontogenetic perspectives of
      'functional dental occlusion' to differentiate continual physiological changes
      occurring over time that require ongoing review, from pathological responses that
      require intervention.

PMID- 24444304
TI  - Large-scale generation of differentiated cells to achieve regenerative medicine.
AB  - The effects of microgravity and fluid dynamic stress on embryoid bodies generated
      from pluripotent stem cells induce and direct their differentiation. Using this
      hydrodynamic effect combined with exogenous factors and three-dimensional
      culture, a new technique has been developed to produce functional, effective, and
      safe hepatocytes for transplantation. The evolution of this technique will lead
      to automated production of a large number of differentiated cells and will
      significantly contribute to regenerative medicine. 

PMID- 24444306
TI  - Influence of photo-curing distance on bond strength and nanoleakage of self
      etching adhesive bonds to enamel and dentin.
AB  - OBJECTIVES: To assess the influence of light-curing unit tip distance on the
      microtensile bond strength (MUTBS) and nanoleakage of self-etching adhesives to
      enamel and dentin. MATERIALS AND METHODS: Flat buccal surfaces were prepared on
      198 bovine incisors. The teeth were randomly assigned into nine groups for MUTBS
      (n = 8) and nanoleakage (n = 3) testing according to the adhesive system
      (Clearfil Protect Bond, Clearfil Tri-S Bond or One Up Bond F Plus) and distance
      from the light-curing tip (0, 3 or 6 mm). The bonded samples were tested in
      tension (0.5 mm/min) and nanoleakage was analyzed using SEM. RESULTS: Clearfil
      Protect Bond exhibited the highest tensile strength on both enamel and dentin.
      Leakage was higher in samples exposed at a distance of 6 mm on enamel and 0 mm on
      dentin. One Up Bond F Plus experienced the greatest amount of nanoleakage on both
      substrates. CONCLUSIONS: Light-curing unit distance did not influence the MUTBS
      of the adhesives, but nanoleakage increased on enamel samples when
      photoactivation occurred at a distance of 6 mm.

PMID- 24444305
TI  - Serum and supplement optimization for EU GMP-compliance in cardiospheres cell
      culture.
AB  - Cardiac progenitor cells (CPCs) isolated as cardiospheres (CSs) and CS-derived
      cells (CDCs) are a promising tool for cardiac cell therapy in heart failure
      patients, having CDCs already been used in a phase I/II clinical trial. Culture
      standardization according to Good Manufacturing Practices (GMPs) is a mandatory
      step for clinical translation. One of the main issues raised is the use of
      xenogenic additives (e.g. FBS, foetal bovine serum) in cell culture media, which
      carries the risk of contamination with infectious viral/prion agents, and the
      possible induction of immunizing effects in the final recipient. In this study,
      B27 supplement and sera requirements to comply with European GMPs were
      investigated in CSs and CDCs cultures, in terms of process yield/efficiency and
      final cell product gene expression levels, as well as phenotype. B27- free CS
      cultures produced a significantly reduced yield and a 10-fold drop in c-kit
      expression levels versus B27+ media. Moreover, autologous human serum (aHS) and
      two different commercially available GMP AB HSs were compared with standard
      research-grade FBS. CPCs from all HSs explants had reduced growth rate, assumed a
      senescent-like morphology with time in culture, and/or displayed a significant
      shift towards the endothelial phenotype. Among three different GMP gamma
      irradiated FBSs (giFBSs) tested, two provided unsatisfactory cell yields, while
      one performed optimally, in terms of CPCs yield/phenotype. In conclusion, the use
      of HSs for the isolation and expansion of CSs/CDCs has to be excluded because of
      altered proliferation and/or commitment, while media supplemented with B27 and
      the selected giFBS allows successful EU GMP-complying CPCs culture. 

PMID- 24444307
TI  - Soyo-san reduces depressive-like behavior and proinflammatory cytokines in
      ovariectomized female rats.
AB  - BACKGROUND: Soyo-san is a traditional oriental medicinal formula, a mixture of 9
      crude drugs, and it has been clinically used for treating mild depressive
      disorders. The role of pro- and anti-inflammatory cytokines in psychiatric
      disorders has been the focus of great research attention in recent years. In the
      present study, we detected the antidepressant effect of soyo-san in the
      ovariectomized and repeated stressed female rats. METHODS: This study was
      designed to evaluate the antidepressant-like effect of soyo-san on the forced
      swimming test (FST). The rats were randomly divided into the following groups:
      the nonoperated and nonstressed group (non-op), the nonoperated and stressed
      group (non-op + ST), the ovariectomized and stress group (OVX) and sham operated
      and stressed group (sham), the ovariectomized and stressed group (OVX + ST), the
      ovariectomized, stressed and soyo-san 100 mg/kg treated group (SOY100) and the
      ovariectomized, stressed and soyo-san 400 mg/kg treated group (SOY400). The rats
      were exposed to immobilization stress (IMO) for 14 day (2 h/14 day), and soyo-san
      (100 mg/kg and 400 mg/kg) was administrated during the same time. In the same
      animals, the levels of corticosterone and interleukin-1-beta (IL-1beta) were
      examined in the serum. Also, the change of IL-1beta expression in brain regions
      was examined after behavior test. RESULTS: In the FST, the lower dose (100 mg/kg)
      of extract was effective in reducing immobility, along with an increase in
      swimming time. The serum levels of corticosterone and IL-1beta in the SOY groups
      were significantly lower than those in the control group. In the brain, the
      expression of IL-1beta positive neurons in the control group were significantly
      increased in the paraventricular nucleus (PVN) and hippocampus compared to the
      non-op. However, soyo-san groups significantly reduced the IL-1beta-ir neurons in
      the PVN and hippocampal regions compared to the control. CONCLUSION: The present
      results demonstrated that soyo-san effectively reduced behavioral and patho
      physiological depression-like responses. TRIAL REGISTRATION: Our results suggest
      that soyo-san may be useful for immune regulator in repeated stress-induced
      ovariectomized female rats.

PMID- 24444308
TI  - The effect of type 1 IFN on human aortic endothelial cell function in vitro:
      relevance to systemic lupus erythematosus.
AB  - Cardiovascular disease (CVD) is an important cause of morbidity and mortality in
      patients with systemic lupus erythematosus. The etiopathogenesis of premature CVD
      is not fully understood, but recently interferon-alpha (IFNalpha) has been
      implicated as a contributing factor. Since IFNalpha has been associated with both
      disease activity and endothelial dysfunction in lupus patients, we aimed to
      determine whether IFNalpha has direct effects on human aortic endothelial cell
      (HAoEC) function in vitro. We studied the function of IFNalpha2b-treated HAoECs
      in terms of cell proliferation, capillary-like network formation, and nitric
      oxide (NO) generation. Changes in gene expression were also analyzed using an
      exon gene array. IFNalpha2b regulated the expression of 198 genes, including
      recognized interferon-stimulated genes (ISGs). Gene ontology analysis showed over
      representation of genes involved in antigen presentation and host response to
      virus but no significant changes in clusters of genes recognized as important in
      endothelial cell activation or dysfunction. HAoEC proliferation, tubule
      formation, and NO bioavailability were unchanged, suggesting that IFNalpha in
      isolation does not have a direct impact on aortic endothelial cell function.

PMID- 24444309
TI  - Benchmark dose calculation for ordered categorical responses.
AB  - The use of benchmark dose (BMD) calculations for dichotomous or continuous
      responses is well established in the risk assessment of cancer and noncancer
      endpoints. In some cases, responses to exposure are categorized in terms of
      ordinal severity effects such as none, mild, adverse, and severe. Such responses
      can be assessed using categorical regression (CATREG) analysis. However, while
      CATREG has been employed to compare the benchmark approach and the no-adverse
      effect-level (NOAEL) approach in determining a reference dose, the utility of
      CATREG for risk assessment remains unclear. This study proposes a CATREG model to
      extend the BMD approach to ordered categorical responses by modeling severity
      levels as censored interval limits of a standard normal distribution. The BMD is
      calculated as a weighted average of the BMDs obtained at dichotomous cutoffs for
      each adverse severity level above the critical effect, with the weights being
      proportional to the reciprocal of the expected loss at the cutoff under the
      normal probability model. This approach provides a link between the current BMD
      procedures for dichotomous and continuous data. We estimate the CATREG parameters
      using a Markov chain Monte Carlo simulation procedure. The proposed method is
      demonstrated using examples of aldicarb and urethane, each with several
      categories of severity levels. Simulation studies comparing the BMD and BMDL
      (lower confidence bound on the BMD) using the proposed method to the
      correspondent estimates using the existing methods for dichotomous and continuous
      data are quite compatible; the difference is mainly dependent on the choice of
      cutoffs for the severity levels. 

PMID- 24444310
TI  - Human blood dendritic cell subsets exhibit discriminative pattern recognition
      receptor profiles.
AB  - Dendritic cells (DCs) operate as the link between innate and adaptive immunity.
      Their expression of pattern recognition receptors (PRRs), such as Toll-like
      receptors (TLRs) and C-type lectin receptors (CLRs), enables antigen recognition
      and mediates appropriate immune responses. Distinct subsets of human DCs have
      been identified; however their expression of PRRs is not fully clarified.
      Expressions of CLRs by DC subpopulations, in particular, remain elusive. This
      study aimed to identify and compare PRR expressions on human blood DC subsets,
      including CD1c(+) , CD141(+) and CD16(+) myeloid DCs and CD123(+) plasmacytoid
      DCs, in order to understand their capacity to recognize different antigens as
      well as their responsiveness to PRR-directed targeting. Whole blood was obtained
      from 13 allergic and six non-allergic individuals. Mononuclear cells were
      purified and multi-colour flow cytometry was used to assess the expression of 10
      CLRs and two TLRs on distinct DC subsets. PRR expression levels were shown to
      differ between DC subsets for each PRR assessed. Furthermore, principal component
      analysis and random forest test demonstrated that the PRR profiles were
      discriminative between DC subsets. Interestingly, CLEC9A was expressed at lower
      levels by CD141(+) DCs from allergic compared with non-allergic donors. The
      subset-specific PRR expression profiles suggests individual responsiveness to PRR
      targeting and supports functional specialization. 

PMID- 24444312
TI  - Effects of carbon sources and amines on induction of trichothecene production by
      Fusarium asiaticum in liquid culture.
AB  - Fusarium asiaticum infects cereal crops and produces trichothecenes such as
      deoxynivalenol and nivalenol. To determine the trichothecene induction mechanism,
      effects of carbon sources on the production of deoxynivalenol, nivalenol, 3
      acetyl deoxynivalenol (3ADON), and 4-acetyl nivalenol (4ANIV) were examined in
      liquid cultures incubated with various strains. Sucrose supported significantly
      higher levels of acetylated trichothecene production in all strains than did the
      other carbon sources. Structural isomers of sucrose did not induce trichothecene
      production. The inducing effect of sucrose on trichothecene production was lost
      after the carbon source in the culture medium changed from sucrose to maltose in
      the process of incubation. Tri4 and Tri5 expressions were specifically up
      regulated in the sucrose-containing medium and down-regulated with sucrose
      exhaustion. These findings suggest that F. asiaticum recognizes sucrose molecules
      and regulates Tri gene expression and trichothecene production. Moreover, an
      accelerating effect on trichothecene production by acidification of the culture
      medium containing specific amines during fungal incubation was exhibited only in
      the presence of sucrose in the medium. F. asiaticum induces trichothecene
      production in the presence of sucrose and accelerates the production when the
      medium containing specific amines is acidified during incubation.

PMID- 24444311
TI  - Cell-selective knockout and 3D confocal image analysis reveals separate roles for
      astrocyte-and endothelial-derived CCL2 in neuroinflammation.
AB  - BACKGROUND: Expression of chemokine CCL2 in the normal central nervous system
      (CNS) is nearly undetectable, but is significantly upregulated and drives
      neuroinflammation during experimental autoimmune encephalomyelitis (EAE), an
      animal model of multiple sclerosis which is considered a contributing factor in
      the human disease. As astrocytes and brain microvascular endothelial cells (BMEC)
      forming the blood-brain barrier (BBB) are sources of CCL2 in EAE and other
      neuroinflammatory conditions, it is unclear if one or both CCL2 pools are
      critical to disease and by what mechanism(s). METHODS: Mice with selective CCL2
      gene knockout (KO) in astrocytes (Astro KO) or endothelial cells (Endo KO) were
      used to evaluate the respective contributions of these sources to
      neuroinflammation, i.e., clinical disease progression, BBB damage, and
      parenchymal leukocyte invasion in a myelin oligodendrocyte glycoprotein peptide
      (MOG35-55)-induced EAE model. High-resolution 3-dimensional (3D)
      immunofluorescence confocal microscopy and colloidal gold immuno-electron
      microscopy were employed to confirm sites of CCL2 expression, and 3D
      immunofluorescence confocal microscopy utilized to assess inflammatory responses
      along the CNS microvasculature. RESULTS: Cell-selective loss of CCL2
      immunoreactivity was demonstrated in the respective KO mice. Compared to wild
      type (WT) mice, Astro KO mice showed reduced EAE severity but similar onset,
      while Endo KO mice displayed near normal severity but significantly delayed
      onset. Neither of the KO mice showed deficits in T cell proliferation, or IL-17
      and IFN-gamma production, following MOG35-55 exposure in vitro, or altered MOG
      major histocompatibility complex class II tetramer binding. 3D confocal imaging
      further revealed distinct actions of the two CCL2 pools in the CNS. Astro KOs
      lacked the CNS leukocyte penetration and disrupted immunostaining of CLN-5 at the
      BBB seen during early EAE in WT mice, while Endo KOs uniquely displayed
      leukocytes stalled in the microvascular lumen. CONCLUSIONS: These results point
      to astrocyte and endothelial pools of CCL2 each regulating different stages of
      neuroinflammation in EAE, and carry implications for drug delivery in
      neuroinflammatory disease.

PMID- 24444313
TI  - Improvement of experimental testing and network training conditions with genome
      wide microarrays for more accurate predictions of drug gene targets.
AB  - BACKGROUND: Genome-wide microarrays have been useful for predicting chemical
      genetic interactions at the gene level. However, interpreting genome-wide
      microarray results can be overwhelming due to the vast output of gene expression
      data combined with off-target transcriptional responses many times induced by a
      drug treatment. This study demonstrates how experimental and computational
      methods can interact with each other, to arrive at more accurate predictions of
      drug-induced perturbations. We present a two-stage strategy that links microarray
      experimental testing and network training conditions to predict gene
      perturbations for a drug with a known mechanism of action in a well-studied
      organism. RESULTS: S. cerevisiae cells were treated with the antifungal,
      fluconazole, and expression profiling was conducted under different biological
      conditions using Affymetrix genome-wide microarrays. Transcripts were filtered
      with a formal network-based method, sparse simultaneous equation models and Lasso
      regression (SSEM-Lasso), under different network training conditions. Gene
      expression results were evaluated using both gene set and single gene target
      analyses, and the drug's transcriptional effects were narrowed first by pathway
      and then by individual genes. Variables included: (i) Testing conditions-
      exposure time and concentration and (ii) Network training conditions--training
      compendium modifications. Two analyses of SSEM-Lasso output--gene set and single
      gene--were conducted to gain a better understanding of how SSEM-Lasso predicts
      perturbation targets. CONCLUSIONS: This study demonstrates that genome-wide
      microarrays can be optimized using a two-stage strategy for a more in-depth
      understanding of how a cell manifests biological reactions to a drug treatment at
      the transcription level. Additionally, a more detailed understanding of how the
      statistical model, SSEM-Lasso, propagates perturbations through a network of gene
      regulatory interactions is achieved.

PMID- 24444315
TI  - Are resilience and maternal sense of coherence associated with gingival status in
      adolescents from low-income families?
AB  - BACKGROUND: The capacity to overcome social disadvantages and maintain oral
      health through psychosocial processes remains poorly understood in children. AIM:
      This study assessed the relationship of children's resilience and maternal sense
      of coherence (SOC) with gingival status in children from low-income families.
      METHODS: A cross-sectional study was conducted on 190 schoolchildren aged 11-12
      years and their mothers. Family socioeconomic characteristics and housing
      conditions, maternal and children's oral cleanliness behaviours (tooth brushing
      and dental floss use), maternal SOC, children's resilience, and demographic data
      were collected through interviews with children and their mothers. Validated
      versions of Antonovsky's scale and the resilience scale were used to assess
      mother's SOC and children's resilience. Gingival status and dental plaque of
      children were evaluated through clinical examinations using bleeding on probing
      index and plaque index. Statistical analysis included Pearson's correlation and
      hierarchical multinomial ordinal logistic regression analyses. RESULTS: The mean
      frequency of gingival bleeding in the sample was 8.4% (SD: 8.5). Children with
      higher levels of resilience showed 31% lower odds of gingival bleeding (OR: 0.7;
      95% CI: 0.4-0.9) after adjustment for socioeconomic characteristics, children's
      and mothers' use of dental floss. CONCLUSIONS: Children's resilience was a
      psychosocial factor associated with gingival conditions.

PMID- 24444314
TI  - Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in
      cardiomyocytes: the role of mitochondria.
AB  - AMP-kinase (AMPK) activation reduces cardiac hypertrophy, although underlying
      molecular mechanisms remain unclear. In this study, we elucidated the anti
      hypertrophic action of metformin, specifically, the role of the AMPK/eNOS/p53
      pathway. H9c2 rat cardiomyocytes were treated with angiotensin II (AngII) for 24
      hrs in the presence or absence of metformin (AMPK agonist), losartan [AngII type
      1 receptor (AT1R) blocker], Nomega-nitro-L-arginine methyl ester (L-NAME, pan-NOS
      inhibitor), splitomicin (SIRT1 inhibitor) or pifithrin-alpha (p53 inhibitor).
      Results showed that treatment with metformin significantly attenuated AngII
      induced cell hypertrophy and death. Metformin attenuated AngII-induced activation
      (cleavage) of caspase 3, Bcl-2 down-regulation and p53 up-regulation. It also
      reduced AngII-induced AT1R up-regulation by 30% (P < 0.05) and enhanced AMPK
      phosphorylation by 99% (P < 0.01) and P-eNOS levels by 3.3-fold (P < 0.01).
      Likewise, losartan reduced AT1R up-regulation and enhanced AMPK phosphorylation
      by 54% (P < 0.05). The AMPK inhibitor, compound C, prevented AT1R down
      regulation, indicating that metformin mediated its effects via AMPK activation.
      Beneficial effects of metformin and losartan converged on mitochondria that
      demonstrated high membrane potential (Deltapsim ) and low permeability transition
      pore opening. Thus, this study demonstrates that the anti-hypertrophic effects of
      metformin are associated with AMPK-induced AT1R down-regulation and prevention of
      mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.

PMID- 24444316
TI  - Reviews and perspectives.

PMID- 24444317
TI  - The role of cognition in outcome in schizophrenia and related disorders.

PMID- 24444318
TI  - Neurocognition: clinical and functional outcomes in schizophrenia.
AB  - Schizophrenia is characterized by significant heterogeneity in outcome. The last
      decades have witnessed a significant interest in identifying factors that can
      moderate or influence clinical and functional outcomes in people with
      schizophrenia. One factor of particular interest is neurocognition, as
      performance on various measures of cognitive abilities, such as memory,
      attention, and executive functions, have been consistently related to functional
      outcome and, to a lesser extent, clinical outcome. This review aims to provide an
      up-to-date description of recent studies examining the association between
      neurocognition and clinical and (or) functional outcomes. In the first section,
      studies examining neurocognitive performance in relation to clinical outcome are
      examined. When clinical outcome is defined dichotomously (for example, comparing
      remitted and nonremitted), verbal memory performance consistently exhibits a
      strong association with clinical status, with the poor outcome group showing the
      largest deficits. In the second section, studies exploring the relation between
      neurocognition and various dimensions of functional outcome are reviewed. These
      dimensions include independent living, social functioning, and vocational
      functioning, among others. Again, a strong link between neurocognitive deficits
      and impairments in several aspects of functioning clearly emerges from this
      review. Finally, several measurement issues are discussed that pertain to the
      need to standardize definitions of clinical and (or) functional outcomes, the
      importance of defining cognitive domains consistently across studies, and
      distinguishing between one's competence to perform tasks and what one actually
      does in everyday life. Addressing these measurement issues will be key to studies
      examining the development of effective interventions targeting neurocognitive
      functions and their impact on clinical and functional outcomes. 

PMID- 24444319
TI  - Cognition, function, and disability in patients with schizophrenia: a review of
      longitudinal studies.
AB  - This paper aims to review longitudinal studies assessing the impact of cognition
      on function in patients with schizophrenia. PubMed and Scholars Portal were
      searched using search terms related to schizophrenia, cognition, function, and
      longitudinal studies. Some functional abilities have been studied more than
      others. Some studies suggest that the impact of cognition on function depends on
      the severity of baseline cognitive deficits. Other studies suggest that the
      impact of cognition on function depend on what phase of the illness the patient
      is in or what stage in that particular function the patient is involved in.
      Finally, few studies assessed interactions between cognition and other aspects of
      schizophrenia in predicting function, such as functional capacity, insight,
      motivation, and negative symptoms. More longitudinal and comprehensive studies
      are needed. A focus on community living is of high public significance as
      patients with schizophrenia continue to grow old. Future studies should also
      focus on the longitudinal interactions between cognition and other dimensions of
      schizophrenia as well as on the biological factors that underlie these
      interactions. 

PMID- 24444320
TI  - Neurocognitive vulnerability: suicidal and homicidal behaviours in patients with
      schizophrenia.
AB  - OBJECTIVE: Schizophrenia is associated with an increase in the risk of both
      homicide and suicide. The objectives of this study were to systematically review
      all published articles that examined the relation between neurocognitive deficits
      and suicidal or homicidal behaviours in schizophrenia, and to identify
      vulnerabilities in suicidal and homicidal behaviour that may share a common
      pathway in schizophrenia. METHODS: A systematic review of the literature was
      performed using MEDLINE to include all studies published up to August 31, 2012.
      RESULTS: Among the 1760 studies, 7 neuropsychological and 12 brain imaging
      studies met the selection criteria and were included in the final analysis. The
      neuropsychological and functional neuroimaging studies were inconclusive. The
      structural imaging studies reported various alterations in patients with
      schizophrenia and a history of homicidal behaviour, including: reduced inferior
      frontal and temporal cortices, increased mediodorsal white matter, and increased
      amygdala volumes. Patients with a history of suicidal acts showed volumetric
      reductions in left orbitofrontal and superior temporal cortices, while right
      amygdala volume was increased, though, these findings have rarely been
      replicated. Finally, no study has directly compared neurocognitive markers of
      suicidal and homicidal risk. CONCLUSION: These results suggest that brain
      alterations, in addition to those associated with schizophrenia, may predispose
      some patients to a higher risk of homicide or suicide in particular
      circumstances. Moreover, some of these alterations may be shared between
      homicidal and suicidal patients. However, owing to several limitations, including
      the small number of available studies, no firm conclusions can be drawn and
      further investigations are necessary.

PMID- 24444321
TI  - Characterizing suicide in Toronto: an observational study and cluster analysis.
AB  - OBJECTIVE: To determine whether people who have died from suicide in a large
      epidemiologic sample form clusters based on demographic, clinical, and
      psychosocial factors. METHOD: We conducted a coroner's chart review for 2886
      people who died in Toronto, Ontario, from 1998 to 2010, and whose death was ruled
      as suicide by the Office of the Chief Coroner of Ontario. A cluster analysis
      using known suicide risk factors was performed to determine whether suicide
      deaths separate into distinct groups. Clusters were compared according to person-
      and suicide-specific factors. RESULTS: Five clusters emerged. Cluster 1 had the
      highest proportion of females and nonviolent methods, and all had depression and
      a past suicide attempt. Cluster 2 had the highest proportion of people with a
      recent stressor and violent suicide methods, and all were married. Cluster 3 had
      mostly males between the ages of 20 and 64, and all had either experienced recent
      stressors, suffered from mental illness, or had a history of substance abuse.
      Cluster 4 had the youngest people and the highest proportion of deaths by jumping
      from height, few were married, and nearly one-half had bipolar disorder or
      schizophrenia. Cluster 5 had all unmarried people with no prior suicide attempts,
      and were the least likely to have an identified mental illness and most likely to
      leave a suicide note. CONCLUSIONS: People who die from suicide assort into
      different patterns of demographic, clinical, and death-specific characteristics.
      Identifying and studying subgroups of suicides may advance our understanding of
      the heterogeneous nature of suicide and help to inform development of more
      targeted suicide prevention strategies.

PMID- 24444322
TI  - Multiple informant agreement of child, parent, and teacher ratings of child
      anxiety within community samples.
AB  - OBJECTIVE: Extant research concerning the degree of multiple informant (that is,
      parent, clinician, teacher, and child) agreement for child anxiety ratings
      generally uses clinical samples, and results have been mixed. METHOD: Our study
      used a community sample of public school children (n = 1039) to investigate child
      (self), parent, and teacher reports of child anxiety across 3 time points
      (pretreatement, posttreatment, and follow-up) in 3 independent school prevention
      and intervention trials. RESULTS: Results showed that parents and teachers had
      high informant agreement for ratings on anxiety across the 3 time points (r =
      0.95 to 0.96, P < 0.001); agreement between parent and child (self) reports and
      between teacher and child (self) reports consistently showed lower agreement
      across the 3 time points (r = 0.14 and 0.28, respectively, P < 0.001). Group
      differences were also significant for sex and grade, whereby females more
      commonly self-reported higher anxiety and children in grades 3 and 4 self
      reported higher anxiety, compared with students in grades 5 to 7. CONCLUSION:
      Correlations between parent and teacher with child ratings were poor over 3 time
      points, and significant differences were found for sex and grade. Research is
      needed to understand reasons for poor concordance between parent, child, and
      teacher ratings of anxiety for all children.

PMID- 24444324
TI  - Do patients really prefer individual outpatient follow-up visits, compared with
      group medical visits?
AB  - OBJECTIVE: Access to outpatient psychiatric care remains problematic in Canada.
      We have been using group medical visits (GMV) to treat psychiatric outpatients
      with mood and anxiety disorders. Our study aimed to show that patients are
      similarly satisfied with GMV and individual psychiatric treatment, hence the
      concern that patients truly prefer individual treatment may be unfounded. METHOD:
      Our study compared patient satisfaction in people who have had previous
      individual psychiatric care and are now receiving GMV to determine whether there
      is a treatment preference. RESULTS: Questionnaire data were analyzed using
      repeated measures ANOVA. The ANOVAs showed no differences in patients'
      experiences with individual treatment, compared with GMV. In addition, we found
      when asked directly, most patients preferred GMV or had no treatment preference.
      CONCLUSIONS: These findings indicate that patients' perspectives of individual
      psychiatric treatment and GMV are roughly equal. This suggests that the method of
      GMV deserves further study and comparison with other clinical models of
      psychiatric outpatient treatment.

PMID- 24444323
TI  - Do psychopathic traits assessed in mid-adolescence predict mental health,
      psychosocial, and antisocial, including criminal outcomes, over the subsequent 5
      years?
AB  - OBJECTIVE: To determine whether psychopathic traits assessed in mid-adolescence
      predicted mental health, psychosocial, and antisocial (including criminal)
      outcomes 5 years later and would thereby provide advantages over diagnosing
      conduct disorder (CD). METHOD: Eighty-six women and 61 men were assessed in mid
      adolescence when they first contacted a clinic for substance misuse and were
      reassessed 5 years later. Assessments in adolescence include the Psychopathy
      Checklist-Youth Version (PCL-YV), and depending on their age, either the Kiddie
      Schedule for Affective Disorders and Schizophrenia for School-Aged Children or
      the Structured Clinical Interview for the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (SCID). Assessments in early adulthood included
      the SCID, self-reports of psychosocial functioning, aggressive behaviour, and
      criminality and official criminal records. RESULTS: The antisocial facet score
      positively predicted the number of anxiety symptoms and likelihood of receiving
      treatment for substance use disorders (SUDs). Lifestyle and antisocial facet
      scores negatively predicted Global Assessment of Functioning scores. By contrast,
      the interpersonal score and male sex independently and positively predicted the
      number of months worked or studied, as did the interaction of Lifestyle * Sex
      indicating that among men, but not women, an increase in lifestyle facet score
      was associated with less time worked or studied. Interpersonal and antisocial
      scores positively predicted school drop-out. Antisocial facet scores predicted
      the number of symptoms of antisocial personality disorder, alcohol and SUDs, and
      violent and nonviolent criminality but much more strongly among males than
      females. Predictions from numbers of CD symptoms were similar. CONCLUSIONS:
      Psychopathic traits among adolescents who misuse substances predict an array of
      outcomes over the subsequent 5 years. Information on the levels of these traits
      may be useful for planning treatment.

PMID- 24444325
TI  - Is the effect of compulsory community treatment on preventable deaths from
      physical disorders mediated by better access to specialized medical procedures?
AB  - OBJECTIVES: Compulsory community treatment has been shown to reduce preventable
      deaths from physical disorders-these causes being up to 10 times more common than
      suicide in psychiatric patients. We investigated whether this was mediated by
      better access to specialized medical procedures. METHOD: All patients on
      compulsory community treatment for over 11 years were compared with matched
      control subjects using linked administrative health data from Western Australia
      (state population of about 2.24 million). Outcomes were access to
      revascularization and other specialized procedures at 1-, 2-, and 3-year follow
      up. Logistic regression was used to adjust for demographics, prior health service
      use, diagnosis, and length of psychiatric history. RESULTS: There were 2757
      patients and 2687 control subjects (total n = 5444). Sixty-five per cent were
      males (n = 3522), and the average age was 36 years (SD 13.2). Most had
      schizophrenia or other nonaffective psychoses (74%), followed by affective
      disorders (26%). At 2-year follow-up, 2% (n = 53) of patients and 2.6% (n = 69)
      of control subjects had undergone a specialized intervention. Compulsory
      community treatment did not result in greater access to specialized procedures at
      all 3 time points even after adjusting for potential confounders. CONCLUSIONS:
      Greater access to specialized procedures does not explain the reduced mortality
      from preventable physical illness that had been reported in patients on community
      treatment orders. There must be other explanations for this finding, such as
      mental health staff facilitating access to chronic disease management in primary
      care. This warrants further research.

PMID- 24444326
TI  - Vacuum assisted birth and risk for cerebral complications in term newborn
      infants: a population-based cohort study.
AB  - BACKGROUND: Few studies have focused on cerebral complications among newborn
      infants delivered by vacuum extraction (VE). The aim of this study was to
      determine the risk for intracranial haemorrhage and/or cerebral dysfunction in
      newborn infants delivered by VE and to compare this risk with that after cesarean
      section in labour (CS) and spontaneous vaginal delivery, respectively. METHODS:
      Data was obtained from Swedish national registers. In a population-based cohort
      from 1999 to 2010 including all singleton newborn infants delivered at term after
      onset of labour by VE (n = 87,150), CS (75,216) or spontaneous vaginal delivery
      (n = 851,347), we compared the odds for neonatal intracranial haemorrhage,
      traumatic or non-traumatic, convulsions or encephalopathy. Logistic regressions
      were used to calculate adjusted (for major risk factors and indication) odds
      ratios (AOR), using spontaneous vaginal delivery as reference group. RESULTS: The
      rates of traumatic and non-traumatic intracranial hemorrhages were 0.8/10,000 and
      3.8/1,000. VE deliveries provided 58% and 31.5% of the traumatic and non
      traumatic cases, giving a ten-fold risk [AOR 10.05 (4.67-21.65)] and double risk
      [AOR 2.23 (1.57-3.16)], respectively. High birth weight and short mother were
      associated with the highest risks. Infants delivered by CS had no increased risk
      for intracranial hemorrhages. The risks for convulsions or encephalopathy were
      similar among infants delivered by VE and CS, exceeding the OR after non-assisted
      spontaneous vaginal delivery by two-to-three times. CONCLUSION: Vacuum assisted
      delivery is associated with increased risk for neonatal intracranial hemorrhages.
      Although causality could not be established in this observational study, it is
      important to be aware of the increased risk of intracranial hemorrhages in VE
      deliveries, particularly in short women and large infants. The results warrant
      further studies in decision making and conduct of assisted vaginal delivery.

PMID- 24444327
TI  - Bench to bedside: it's all about the model.
AB  - Continual improvement and targeting of large animal models with contemporary
      technology augment their accuracy and value. New discoveries within the models
      contribute to reliable results with reduced variability. Despite the importance
      of large animal stem cell models to biomedical advances, the knowledge base
      surrounding them is relatively limited compared with that of human and rodents.
      The series of investigations presented by Niada and colleagues helps to meet this
      essential element of large animal models with information about in vitro behavior
      of porcine adipose-derived stem cells from two different harvest sites as well as
      their responses to implant materials and porcine serum. 

PMID- 24444328
TI  - Cardiac right-to-left shunt subtypes in Chinese patients with cryptogenic
      strokes: a multicenter case-control study.
AB  - BACKGROUND AND PURPOSE: Data on the possible association between cardiac right-to
      left shunt (RLS) and cryptogenic stroke are lacking in Asians. RLS and its
      subtypes in Chinese cryptogenic stroke patients were investigated. METHODS:
      Patients (n = 153, mean age 42 +/- 10 years, 81 male) with cryptogenic stroke
      from four medical centers in China and 135 healthy volunteers (mean age 34 +/- 8
      years, 54 male) were recruited. Contrast transcranial Doppler was used to assess
      the prevalence of RLS. A three-level RLS categorization was applied as follows:
      none, 0 microbubbles (MBs); small, 1-25 MBs; and large, >25 MBs. RLS was
      considered latent if it occurred only after the Valsalva maneuver or permanent
      when it occurred also during normal respiration. RESULTS: Overall, RLS (P =
      0.02), large RLS (P < 0.001) and permanent RLS (P = 0.02) were more frequently
      detected in patients with cryptogenic stroke than in healthy volunteers. The
      prevalences of small RLS and latent RLS in the two groups were similar (22% vs.
      21% and 11% vs. 10%, respectively). The proportion of large RLSs amongst the
      subjects with RLS was much higher in the patient group than in healthy volunteers
      (45% vs. 18%, P < 0.001), whilst the proportion of permanent RLS was similar (72%
      vs. 64%, P = 0.11). Most large RLSs in the patient group (22/27, 81%) were
      permanent RLSs. CONCLUSIONS: Cardiac RLS is associated with cryptogenic stroke in
      Chinese. However, the higher prevalence of overall RLS in the patient group was
      mainly due to the increased proportion of large RLSs. The results only support
      large RLSs as a pathological condition.

PMID- 24444329
TI  - Petri net-based modelling of human-automation conflicts in aviation.
AB  - Analyses of aviation safety reports reveal that human-machine conflicts induced
      by poor automation design are remarkable precursors of accidents. A review of
      different crew-automation conflicting scenarios shows that they have a common
      denominator: the autopilot behaviour interferes with the pilot's goal regarding
      the flight guidance via 'hidden' mode transitions. Considering both the human
      operator and the machine (i.e. the autopilot or the decision functions) as
      agents, we propose a Petri net model of those conflicting interactions, which
      allows them to be detected as deadlocks in the Petri net. In order to test our
      Petri net model, we designed an autoflight system that was formally analysed to
      detect conflicting situations. We identified three conflicting situations that
      were integrated in an experimental scenario in a flight simulator with 10 general
      aviation pilots. The results showed that the conflicts that we had a-priori
      identified as critical had impacted the pilots' performance. Indeed, the first
      conflict remained unnoticed by eight participants and led to a potential
      collision with another aircraft. The second conflict was detected by all the
      participants but three of them did not manage the situation correctly. The last
      conflict was also detected by all the participants but provoked typical
      automation surprise situation as only one declared that he had understood the
      autopilot behaviour. These behavioural results are discussed in terms of workload
      and number of fired 'hidden' transitions. Eventually, this study reveals that
      both formal and experimental approaches are complementary to identify and assess
      the criticality of human-automation conflicts. Practitioner Summary: We propose a
      Petri net model of human-automation conflicts. An experiment was conducted with
      general aviation pilots performing a scenario involving three conflicting
      situations to test the soundness of our formal approach. This study reveals that
      both formal and experimental approaches are complementary to identify and assess
      the criticality conflicts. 

PMID- 24444330
TI  - Primary structural features of SR-like protein acinusS govern the phosphorylation
      mechanism by SRPK2.
AB  - SRPKs (serine/arginine protein kinases) are highly specific kinases that
      recognize and phosphorylate RS (Arg-Ser) dipeptide repeats. It has been shown
      previously that SRPK1 phosphorylates the RS domain of SRSF1 (serine/arginine
      splicing factor 1) at multiple sites using a directional and processive
      mechanism. Such ability to processively phosphorylate substrates is proposed to
      be an inherent characteristic of SRPKs. SRPK2 is highly related to SRPK1 in
      sequence and in vitro properties, yet it has been shown to have distinct
      substrate specificity and physiological function in vivo. To study the molecular
      basis for substrate specificity of SRPK2, we investigated the roles of the non
      kinase regions and a conserved docking groove of SRPK2 in the recognition and
      phosphorylation of different substrates: SRSF1 and acinusS. Our results reveal
      that a conserved electronegative docking groove in SRPK2, but not its non-kinase
      regions, is responsible for substrate binding regardless of their identities.
      Although SRPK2 phosphorylates SRSF1 in a processive manner as predicted, an
      electronegative region on acinusS restricts SRPK2 phosphorylation to a single
      specific site despite the presence of multiple RS dipeptides. These results
      suggest that primary structural elements on the substrates serve as key
      regulatory roles in determining the phosphorylation mechanism of SRPK2.

PMID- 24444331
TI  - Radiographic thoracic anatomy of the ring-tailed lemur (Lemur catta).
AB  - BACKGROUND: The ring-tailed lemur (Lemur catta) is a quadruped arboreal primate
      primarily distributed in south and south-western Madagascar. This study was
      carried out to describe the normal radiographic thoracic anatomy of the ring
      tailed lemur as a reference for clinical use. METHODS: Radiography of the thorax
      was performed in 15 captive ring-tailed lemurs during their annual health
      examinations. RESULTS: Normal radiographic reference ranges for thoracic
      structures were established and ratios were calculated, such as the vertebral
      heart score (VHS). The mean VHS on the right lateral and dorsoventral views was
      8.92 +/- 0.47 and 9.42 +/- 0.52, respectively. CONCLUSIONS: Differences exist in
      the normal radiographic thoracic anatomy of primates. Knowledge of the normal
      radiographic thoracic anatomy of individual species is important and fundamental
      to assist in clinical cases and for accurate diagnosis of diseases.

PMID- 24444332
TI  - Aggregate human health risk assessment from dust of daily life in the urban
      environment of Beijing.
AB  - Because of the high emissions of polycyclic aromatic hydrocarbons (PAHs) into the
      environment by the increasing number of vehicles in Beijing and the absorption of
      these PAHs onto particulates, the performance of a preliminary health risk
      assessment of the aggregate exposure to PAHs of urban citizens in daily life is
      very important. Urban dust can be used to examine the aggregation of atmospheric
      particulates from local pollution sources over a long time period and the direct
      exposure of the urban human population. The environment's correlative with
      clothing, dining, residing, and traveling in urban daily life was assessed using
      exposure-receptor-oriented analysis. The multipathway exposure model was used to
      simulate the lifetime exposure of a female citizen to PAHs in dust. All of the
      PAH concentrations in dust for each behavior and its correlative environment in
      Beijing were acceptable because all of the carcinogenic risks of PAHs in the dust
      were approximately 1.0 * 10(-6). The dominant induced carcinogenic risks in the
      dust were Benzo(a)pyrene and Dibenzo(a,h)anthracene. The main carcinogenic risk
      routes for humans were dermal contact and oral intake, which contributed on
      average 99.78% of the risk. Indoor risk is especially important, as the
      decoration and height within the building were important impact factors for
      carcinogenic risk induced by indoor PAHs. For people living in an urban area, a
      healthy lifestyle includes less decoration per room, living on a low floor,
      wearing a respirator, and reducing exposed skin area when traveling.

PMID- 24444334
TI  - Effects of feeding different roughage components to sows in gestation on
      bacteriological and immunological parameters in colostrum and immune response of
      piglets.
AB  - In piglet production, Escherichia coli (E. coli) and the presence of
      lipopolysaccharides (LPS) were considered as predominant causative agents in the
      aetiology of important diseases of sows and piglets. The aim of the study was to
      assess the effects of feeding different roughage sources to sows in gestation on
      the microbiota and endotoxin concentration in colostrum and on the specific
      immune response of their piglets. In two trial runs, a total of 144 sows were
      assigned to one of the six dietary treatments: the Control group receiving a
      concentrate diet and five groups with a restrictive supply of the control diet in
      combination with straw (S), hay (H), clover grass silage (GS), maize silage (MS)
      or Jerusalem artichoke (JA). During lactation no roughage was offered. Colostrum
      samples were analysed for bacteriological and immunological parameters. Blood
      samples were taken from two piglets per corresponding litter to examine the
      concentration of C-reactive protein (CRP) and of specific antibodies to LPS of E.
      coli (strain J5). Roughage feeding had an effect neither on the total bacterial
      count nor on the content of E. coli in colostrum of sows. The concentration of
      LPS in colostrum was reduced in Group MS. The concentration of CRP in the
      colostrum samples was low and independent of the feeding regime (max. 9.3 ug/ml).
      However, the administration of roughage components rich in crude fibre (Groups H
      and S) decreased the level of CRP in colostrum significantly. The analysis of the
      specific immunoglobulin to LPS of E. coli (strain J5) showed a higher
      concentration of IgG-anti-LPS in blood serum of piglets from sows of Group JA.
      The results suggest that the inclusion of selected roughage components may have
      the potential to affect the immunocompetence of sows and their corresponding
      piglets. 

PMID- 24444333
TI  - Emerging evidence of the physiological role of hypoxia in mammary development and
      lactation.
AB  - Hypoxia is a physiological or pathological condition of a deficiency of oxygen
      supply in the body as a whole or within a tissue. During hypoxia, tissues undergo
      a series of physiological responses to defend themselves against a low oxygen
      supply, including increased angiogenesis, erythropoiesis, and glucose uptake. The
      effects of hypoxia are mainly mediated by hypoxia-inducible factor 1 (HIF-1),
      which is a heterodimeric transcription factor consisting of alpha and beta
      subunits. HIF-1beta is constantly expressed, whereas HIF-1alpha is degraded under
      normal oxygen conditions. Hypoxia stabilizes HIF-1alpha and the HIF complex, and
      HIF then translocates into the nucleus to initiate the expression of target
      genes. Hypoxia has been extensively studied for its role in promoting tumor
      progression, and emerging evidence also indicates that hypoxia may play important
      roles in physiological processes, including mammary development and lactation.
      The mammary gland exhibits an increasing metabolic rate from pregnancy to
      lactation to support mammary growth, lactogenesis, and lactation. This process
      requires increasing amounts of oxygen consumption and results in localized
      chronic hypoxia as confirmed by the binding of the hypoxia marker pimonidazole
      HCl in mouse mammary gland. We hypothesized that this hypoxic condition promotes
      mammary development and lactation, a hypothesis that is supported by the
      following several lines of evidence: i) Mice with an HIF-1alpha deletion
      selective for the mammary gland have impaired mammary differentiation and lipid
      secretion, resulting in lactation failure and striking changes in milk
      compositions; ii) We recently observed that hypoxia significantly induces HIF
      1alpha-dependent glucose uptake and GLUT1 expression in mammary epithelial cells,
      which may be responsible for the dramatic increases in glucose uptake and GLUT1
      expression in the mammary gland during the transition period from late pregnancy
      to early lactation; and iii) Hypoxia and HIF-1alpha increase the phosphorylation
      of signal transducers and activators of transcription 5a (STAT5a) in mammary
      epithelial cells, whereas STAT5 phosphorylation plays important roles in the
      regulation of milk protein gene expression and mammary development. Based on
      these observations, hypoxia effects emerge as a new frontier for studying the
      regulation of mammary development and lactation. 

PMID- 24444336
TI  - Polymorphous oligodendroglioma of Zulch revisited: a genetically heterogeneous
      group of anaplastic gliomas including tumors of bona fide oligodendroglial
      differentiation.
AB  - A polymorphous variant of oligodendroglioma was described by K.J. Zulch half a
      century ago, and is only very sporadically referred to in the subsequent
      literature. In particular, no comprehensive analysis with respect to clinical or
      genetic features of these tumors is available. From a current perspective, the
      term polymorphous oligodendroglioma (pO) may appear as contradictory in terms, as
      nuclear monotony is a histomorphological hallmark of oligodendrogliomas. For the
      purpose of this study, we defined pO as diffusely infiltrating gliomas felt to be
      of oligodendroglial rather than astrocytic differentiation and characterized by
      the presence of multinucleate tumor giant cells and/or nuclear pleomorphism. In a
      total of nine patients, we identified tumors consistent with this working
      definition. All tumors were high-grade. We characterized these with respect to
      clinical, histomorphological and genetic features. Despite clinical and genetic
      heterogeneity, we identified a subset of tumors of bona fide oligodendroglial
      differentiation as characterized by combined loss of heterozygosity of chromosome
      arms 1p and 19q (LOH 1p19q). Those tumors that lacked LOH 1p19q showed a high
      frequency of IDH1 mutations and loss of alpha thalassemia/mental retardation
      syndrome X-linked gene (ATRX) immunoreactivity, indicating a possible phenotypic
      convergence of true oligodendrogliomas and gliomas of the alternative lengthening
      of telomeres (ALT) pathway. p53 alterations were common irrespective of the 1p19q
      status. Histomorphologically, the tumors featured interspersed bizarre
      multinucleate giant tumor cells, while the background population varied from
      monotonous to significantly pleomorphic. Our findings indicate, that a rare
      polymorphous - or "giant cell" - variant of oligodendroglioma does indeed exist.

PMID- 24444335
TI  - Anti-osteoclastogenic activity of matairesinol via suppression of p38/ERK-NFATc1
      signaling axis.
AB  - BACKGROUND: Matairesinol is a plant lignan present in a wide variety of
      foodstuffs such as seeds, vegetables and fruits. It has various biological
      functions including anti-angiogenic, anti-cancer and anti-fungal activities, but
      its anti-osteoporotic activity, if any, is unknown. METHODS: For osteoclast
      differentiation, primary mouse bone marrow-derived macrophage cells (BMMs) were
      cultured for 4 days in the presence of RANKL and M-CSF with the vehicle (DMSO) or
      matairesinol. Cell cytotoxicity was examined by CCK-8 assay. Gene expression of
      NFATc1, TRAP, OSCAR, v-ATPasev0d2 were observed in the presence or absence of
      matairesinol (10 MUM) for the indicated times. For evaluating the involvement of
      NFATc1 in the anti-osteoclastogenic action of matairesinol, BMMs were infected
      with pMX-IRES-GFP or pMX-IRES-CA-NFATc1-GFP for 8 h with polybrene, and then
      infected BMMs were cultured with M-CSF and RANKL for 4 days in the presence or
      absence of matairesinol (10 MUM). MAPK signaling activation was examined by
      immunoblotting. For measuring the resorptive activity of mature osteoclasts,
      osteoclasts and osteoblasts were co-cultured on BioCoat Osteologic MultiTest
      slides, and treated with matairesinol for 24 h. RESULT: Here we show that
      matairesinol dose-dependently inhibited the RANKL-induced differentiation of BMMs
      into osteoclasts by downregulating RANKL-induced expression and activity of
      NFATc1. Ectopic overexpression of NFATc1 blunted the anti-osteoclastogenic effect
      of matairesinol implicating NFATc1 in the action of matairesinol. Additionally,
      matairesinol blocked the RANKL-induced activation of p38 and ERK in BMMs, but had
      no effect on bone resorption activity in mature osteoclasts. CONCLUSION: Taken
      together, our results suggest that the anti-osteoporotic activity of matairesinol
      could arise from its anti-osteoclastogenic potential via p38/ERK-NFATc1
      signaling, but not by way of anti-resorptive action.

PMID- 24444338
TI  - Anti-interferon beta antibody titers strongly correlate between two bioassays and
      in vivo biomarker expression, and indicates that a titer of 150 TRU/mL is a
      biologically functional cut-point.
AB  - Interferon beta (IFNbeta) is used as a first-line treatment in relapsing
      remitting multiple sclerosis (MS). The occurrence of neutralizing antidrug
      antibodies (NAbs) against IFNbeta may reduce treatment response. Therefore,
      clinical monitoring of NAbs is currently executed using bioassays, but several
      bioassays are available and it is unclear how well their readouts correlate. We
      made a comparison between 2 bioassays; myxovirus resistance protein A (MxA) gene
      expression assay (MGA) and iLiteTM anti-Human IFNbeta bioassay, to measure
      IFNbeta-specific NAb titers in 44 MS patients. We further studied how NAb titers
      affected in vivo transcription of IFN-induced genes myxovirus resistant 1 (MX1)
      and C-X-C motif chemokine 10 (CXCL10), in addition to serum CXCL10 protein
      levels. There were significant correlations between NAb titer levels measured
      with MGA and iLite (Spearman r=0.9368). MX1 and CXCL10 gene expression was
      strongly induced by IFNbeta and NAb positivity significantly reduced this
      expression. A NAb titer of 150 TRU/mL was observed to be a biological cut-point
      applicable to both assays, since MX1 and CXCL10 expression was greatly reduced or
      blocked in patients above this titer level. In conclusion, NAb titers measured
      with the MGA and iLite bioassays are comparable, but the threshold for positivity
      in both assays does not correspond to the biologically functional cut-point. 

PMID- 24444337
TI  - Evidence of promiscuous endothelial binding by Plasmodium falciparum-infected
      erythrocytes.
AB  - The adhesion of infected red blood cells (iRBCs) to human endothelium is
      considered a key event in the pathogenesis of cerebral malaria and other life
      threatening complications caused by the most prevalent malaria parasite
      Plasmodium falciparum. In the past 30 years, 14 endothelial receptors for iRBCs
      have been identified. Exposing 10 additional surface proteins of endothelial
      cells to a mixture of P.  falciparum isolates from three Ghanaian malaria
      patients, we identified seven new iRBC receptors, all expressed in brain vessels.
      This finding strongly suggests that endothelial binding of P.  falciparum iRBCs
      is promiscuous and may use a combination of endothelial surface moieties.

PMID- 24444339
TI  - Are superoxide dismutase 2 and nitric oxide synthase polymorphisms associated
      with idiopathic infertility?
AB  - The aim of this study was to investigate in a case-control study the associations
      between idiopathic infertility and antioxidant gene polymorphisms. One hundred
      ten infertile subjects (58 women and 52 men) with a history of idiopathic
      infertility and 69 fertile subjects (35 women and 34 men) with no history of
      infertility were included by three hospital departments of reproductive biology
      in the NCT01093378 French government clinical trial. Genotyping was assessed by
      real-time polymerase chain reaction with TaqMan assay. We examined genetic
      polymorphisms affecting five antioxidant enzymes: manganese superoxide dismutase
      (MnSOD), myeloperoxidase (MPO), glutathione peroxidase 1 (GPx1), catalase (CAT),
      and endothelial nitric oxide synthase (eNOS). The presence of at least 1 Ala
      MnSOD allele (rs4880) increased significantly the risk of infertility (odds ratio
      [OR] 2.94; 95% confidence interval [CI], 1.14, 7.60; p=0.03) in male subjects.
      Moreover, the presence of 2 G-eNOS allele (rs1799983) increased significantly the
      risk of infertility in both men and women (OR 1.91; 95% CI, 1.04, 3.54; p=0.04).
      Our observations lead to the hypothesis that the genetic susceptibility
      modulating oxidative stress may represent a risk factor for male idiopathic
      infertility.

PMID- 24444340
TI  - Dental Implants in Oral Rehabilitation of A Maxillary Cancer Reconstruction: A
      Case Report.

PMID- 24444341
TI  - TAPBPR isoforms exhibit altered association with MHC class I.
AB  - The tapasin-related protein TAPBPR is a novel component of the antigen processing
      and presentation pathway, which binds to MHC class I coupled with beta2
      microglobulin. We describe six alternatively spliced TAPBPR transcripts from the
      TAPBPL gene and investigate three of these at a protein level. TAPBPR transcripts
      lacking exon 5 result in loss of the membrane proximal IgC domain and loss of
      ability to bind to MHC class I. Alternative acceptor and donor splice sites in
      exon 4 of TAPBPR altered the reading frame in the IgV domain and produced a
      truncated TAPBPR product. An additional exon in the TAPBPL gene was identified
      that encodes extra residues in the cytoplasmic tail of TAPBPR. This longer TAPBPR
      protein interacted with MHC class I but was attenuated in its ability to down
      regulate surface expression of MHC class I. The abundance of these alternative
      transcripts in peripheral blood mononuclear cells and dendritic cells suggests an
      important role of TAPBPR isoforms in vivo.

PMID- 24444342
TI  - Users of mental health services as peer support providers and research
      collaborators.

PMID- 24444349
TI  - The linker between the dimerization and catalytic domains of the CheA histidine
      kinase propagates changes in structure and dynamics that are important for
      enzymatic activity.
AB  - The histidine kinase, CheA, couples environmental stimuli to changes in bacterial
      swimming behavior, converting a sensory signal to a chemical signal in the
      cytosol via autophosphorylation. The kinase activity is regulated in the platform
      of chemotaxis signaling complexes formed by CheW, chemoreceptors, and the
      regulatory domain of CheA. Our previous computational and mutational studies have
      revealed that two interdomain linkers play important roles in CheA's enzymatic
      activity. Of the two linkers, one that connects the dimerization and ATP binding
      domains is essential for both basal autophosphorylation and activation of the
      kinase. However, the mechanistic role of this linker remains unclear, given that
      it is far from the autophosphorylation reaction center (the ATP binding site).
      Here we investigate how this interdomain linker is coupled to CheA's enzymatic
      activity. Using modern nuclear magnetic resonance (NMR) techniques, we find that
      by interacting with the catalytic domain, the interdomain linker initiates long
      range structural and dynamic changes directed toward the catalytic center of the
      autophosphorylation reaction. Subsequent biochemical assays define the functional
      relevance of these NMR-based observations. These findings extend our
      understanding of the chemotaxis signal transduction pathway. 

PMID- 24444351
TI  - Normative data and psychometric properties of the strengths and difficulties
      questionnaire among Japanese school-aged children.
AB  - BACKGROUND: Although child mental health problems are among the most important
      worldwide issues, development of culturally acceptable mental health services to
      serve the clinical needs of children and their families is especially lacking in
      regions outside Europe and North America. The Strengths and Difficulties
      Questionnaire (SDQ), which was developed in the United Kingdom and is now one of
      the most widely used measurement tools for screening child psychiatric symptoms,
      has been translated into Japanese, but culturally calibrated norms for Japanese
      schoolchildren have yet to be established. To this end, we examined the
      applicability of the Japanese versions of the parent and teacher SDQs by
      establishing norms and extending validation of its psychometric properties to a
      large nationwide sample, as well as to a smaller clinical sample. METHODS: The
      Japanese versions of the SDQ were completed by parents and teachers of
      schoolchildren aged 7 to 15 years attending mainstream classes in primary or
      secondary schools in Japan. Data were analyzed to describe the population
      distribution and gender/age effects by informant, cut-off scores according to
      banding, factor structure, cross-scale correlations, and internal consistency for
      24,519 parent ratings and 7,977 teacher ratings from a large nationwide sample.
      Inter-rater and test-retest reliabilities and convergent and divergent validities
      were confirmed for a smaller validation sample (total n = 128) consisting of a
      clinical sample with any mental disorder and community children without any
      diagnoses. RESULTS: Means, standard deviations, and banding of normative data for
      this Japanese child population were obtained. Gender/age effects were significant
      for both parent and teacher ratings. The original five-factor structure was
      replicated, and strong cross-scale correlations and internal reliability were
      shown across all SDQ subscales for this population. Inter-rater agreement was
      satisfactory, test-retest reliability was excellent, and convergent and divergent
      validities were satisfactory for the validation sample, with some differences
      between informants. CONCLUSIONS: This study provides evidence that the Japanese
      version of the SDQ is a useful instrument for parents and teachers as well as for
      research purposes. Our findings also emphasize the importance of establishing
      culturally calibrated norms and boundaries for the instrument's use.

PMID- 24444350
TI  - Passive immunization of macaques with polyclonal anti-SHIV IgG against a
      heterologous tier 2 SHIV: outcome depends on IgG dose.
AB  - BACKGROUND: A key goal for HIV-1 envelope immunogen design is the induction of
      cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will
      not be exposed to strains exactly matching any immunogens due to multiple HIV-1
      quasispecies circulating in the human population worldwide, heterologous SHIV
      challenges are essential for realistic vaccine efficacy testing in primates. We
      assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high
      titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV
      2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had
      elicited SHIVIG. RESULTS: SHIVIG demonstrated binding to HIV Gag, Tat, and Env of
      different clades and competed with the broadly neutralizing antibodies b12,
      VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including
      SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20
      fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this
      polyclonal IgG preparation failed to prevent acquisition after repeated
      intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it
      significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome
      analysis revealed a higher number of transmitted variants at the low dose of 25
      mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG
      demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE)
      at concentrations similar to those observed in plasmas of RMs treated with 25
      mg/kg of SHIVIG. CONCLUSION: Our primate model data suggest a dual role for
      polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.

PMID- 24444352
TI  - How does involvement of a hospice nurse specialist impact on the experience on
      informal caring in palliative care? Perspectives of middle-aged partners bereaved
      through cancer.
AB  - The aim of this study was to retrospectively explore partners' understandings and
      experiences in relation to caring for a loved one with a terminal illness, with a
      particular focus on the role of the hospice nurse specialist (HNS). Participants
      were purposively sampled and recruited through HNS gatekeepers. Seven middle
      aged, bereaved partners participated in semi-structured, qualitative interviews.
      The interviews were audio recorded and transcribed verbatim and data were
      analysed using thematic content analysis. Five main themes emerged regarding the
      impact of the HNS on informal caring: 'the ambivalence of caring', 'the HNS as a
      "confidante" in caring', 'the HNS as a "champion" in support', 'the work of the
      HNS--an unseen benefit' and 'being prepared for death and bereavement'. Findings
      from this study offer new insights into how involvement of a HNS impacts on the
      ability of carers to perform their role as an informal caregiver. Results
      highlight a crucial need for carers to have a clear understanding of all aspects
      of the HNS role so that full benefit is derived from their input. Recruitment of
      experienced and knowledgeable nurses is paramount, but equally important for
      carers is the supportive aspect of the role for which nurses need to demonstrate
      excellent communication skills and an intuitive, caring approach.

PMID- 24444353
TI  - Loss of intrahepatic HBsAg expression predicts sustained response to
      peginterferon and is reflected by pronounced serum HBsAg decline.
AB  - There is a lack of knowledge regarding the effect of peginterferon (PEG-IFN) on
      the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and
      HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy.
      Fifty-two HBeAg-positive and 67 HBeAg-negative CHB patients with paired liver
      biopsies taken at baseline and after 1 year of PEG-IFN therapy were studied.
      After PEG-IFN therapy, HBeAg-negative patients showed a significant reduction in
      both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast,
      a reduction in intrahepatic HBcAg expression was not observed in HBeAg-positive
      patients, while a trend in reduction of intrahepatic HBsAg staining was found (P
      = 0.09). Post-treatment, 7 (13%) HBeAg-positive and 9 (14%) HBeAg-negative
      patients had no expression of intrahepatic HBsAg. Patients without any
      intrahepatic HBsAg expression post-treatment were more likely to achieve a
      combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for
      HBeAg -positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for
      HBeAg-negative CHB): 71% vs 5% for HBeAg-positive (P < 0.001) and 60% vs 16% for
      HBeAg-negative patients (P = 0.004), respectively. Moreover, a more profound
      decline of serum HBsAg was observed in patients with absence of intrahepatic
      HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P =
      0.005 for HBeAg-positive and HBeAg-negative CHB, respectively). In conclusion,
      PEG-IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by
      immunohistochemistry from the liver predicts a sustained response and is
      reflected in a pronounced serum HBsAg decline. 

PMID- 24444354
TI  - Decrease in cytochrome c oxidase reserve capacity diminishes robustness of
      Drosophila melanogaster and shortens lifespan.
AB  - The phenotypic effects of under- and over-expression of CcO (cytochrome c
      oxidase) regulatory subunits IV and Vb were examined in Drosophila melanogaster
      in order to test further the hypothesis that suppression of the activities of
      mitochondrial ETC (electron-transport chain) oxidoreductases retards the aging
      process and extends lifespan. Underexpression of both CcO subunits, induced by
      RNAi, resulted in decreases in the respective mRNA and protein levels, CcO
      holoenzyme activity, rate of mitochondrial respiration, walking speed and the
      lifespan of fruitflies. Overexpression of CcO IV or Vb in young fruitflies
      increased the amount of mRNA, but had no effect on the protein level or CcO
      catalytic activity. On the other hand, in older fruitflies, overexpression of CcO
      Vb, but not CcO IV, elevated the mRNA and protein amounts as well as the CcO
      holoenzyme activity, thereby preventing the typical age-related decline in CcO
      activity. Nevertheless, lifespans of the fruitflies overexpressing CcO IV or Vb
      were neither extended nor shortened. Our results demonstrate that: (i) the
      suppression of CcO function exerts deleterious rather than benign effects on
      fitness and survival, and (ii) the structure/function of CcO, an ETC
      oxidoreductase, can be 're-engineered' in vivo.

PMID- 24444356
TI  - The distinction between risk and hazard: understanding and use in stakeholder
      communication.
AB  - A major issue in all risk communication efforts is the distinction between the
      terms "risk" and "hazard." The potential to harm a target such as human health or
      the environment is normally defined as a hazard, whereas risk also encompasses
      the probability of exposure and the extent of damage. What can be observed again
      and again in risk communication processes are misunderstandings and communication
      gaps related to these crucial terms. We asked a sample of 53 experts from public
      authorities, business and industry, and environmental and consumer organizations
      in Germany to outline their understanding and use of these terms using both the
      methods of expert interviews and focus groups. The empirical study made clear
      that the terms risk and hazard are perceived and used very differently in risk
      communication depending on the perspective of the stakeholders. Several factors
      can be identified, such as responsibility for hazard avoidance, economic
      interest, or a watchdog role. Thus, communication gaps can be reduced to a four
      fold problem matrix comprising a semantic, conceptual, strategic, and control
      problem. The empirical study made clear that risks and hazards are perceived very
      differently depending on the stakeholders' perspective. Their own worldviews
      played a major role in their specific use of the two terms hazards and risks in
      communication. 

PMID- 24444355
TI  - Considerations in designing systems for large scale production of human
      cardiomyocytes from pluripotent stem cells.
AB  - Human pluripotent stem cell (hPSC)-derived cardiomyocytes have attracted
      attention as an unlimited source of cells for cardiac therapies. One of the
      factors to surmount to achieve this is the production of hPSC-derived
      cardiomyocytes at a commercial or clinical scale with economically and
      technically feasible platforms. Given the limited proliferation capacity of
      differentiated cardiomyocytes and the difficulties in isolating and culturing
      committed cardiac progenitors, the strategy for cardiomyocyte production would be
      biphasic, involving hPSC expansion to generate adequate cell numbers followed by
      differentiation to cardiomyocytes for specific applications. This review
      summarizes and discusses up-to-date two-dimensional cell culture, cell-aggregate
      and microcarrier-based platforms for hPSC expansion. Microcarrier-based platforms
      are shown to be the most suitable for up-scaled production of hPSCs.
      Subsequently, different platforms for directing hPSC differentiation to
      cardiomyocytes are discussed. Monolayer differentiation can be straightforward
      and highly efficient and embryoid body-based approaches are also yielding
      reasonable cardiomyocyte efficiencies, whereas microcarrier-based approaches are
      in their infancy but can also generate high cardiomyocyte yields. The optimal
      target is to establish an integrated scalable process that combines hPSC
      expansion and cardiomyocyte differentiation into a one unit operation. This
      review discuss key issues such as platform selection, bioprocess parameters,
      medium development, downstream processing and parameters that meet current good
      manufacturing practice standards. 

PMID- 24444357
TI  - The peripheral chimerism of bone marrow-derived stem cells after transplantation:
      regeneration of gastrointestinal tissues in lethally irradiated mice.
AB  - Bone marrow-derived cells represent a heterogeneous cell population containing
      haematopoietic stem and progenitor cells. These cells have been identified as
      potential candidates for use in cell therapy for the regeneration of damaged
      tissues caused by trauma, degenerative diseases, ischaemia and inflammation or
      cancer treatment. In our study, we examined a model using whole-body irradiation
      and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs)
      to study the repair of haematopoiesis, extramedullary haematopoiesis and the
      migration of green fluorescent protein (GFP(+)) transplanted cells into non
      haematopoietic tissues. We investigated the repair of damage to the BM,
      peripheral blood, spleen and thymus and assessed the ability of this treatment to
      induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non
      haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+)
      cells from GFP transgenic mice successfully repopulated haematopoiesis and the
      haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and
      thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract
      (GIT) following whole-body irradiation. Our results demonstrate that whole-body
      irradiation does not significantly alter the integrity of tissues such as those
      in the small intestine and liver. Whole-body irradiation also induced
      myeloablation and chimerism in tissues, and induced the entry of transplanted
      cells into the small intestine and liver. This result demonstrates that grafted
      BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus,
      these transplanted cells could be used for the long-term treatment of various
      pathologies or as a one-time treatment option if myeloablation-induced chimerism
      alone is not sufficient to induce the entry of transplanted cells into non
      haematopoietic tissues.

PMID- 24444358
TI  - Two cases of multinodular and vacuolating neuronal tumour.
AB  - An unusual multinodular and vacuolating neuronal tumour (MVNT) has been described
      in the cerebral hemispheres of ten patients with adult-onset seizures. We report
      the findings in two cases with similar features, a surgical resection and the
      other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical
      resection for a multinodular non-enhancing frontal white matter lesion causing
      intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the
      age of 71 and MRI scanning revealed extensive multinodular non-enhancing white
      matter lesions in the temporal lobe. There was no history of epilepsy and post
      mortem histology confirmed MND.Macroscopically multiple small grey well-formed,
      discrete and coalescent nodules were seen in the deep cortex and subcortical
      white matter. On histology, mature-looking neurons with large cytoplasmic
      vacuoles were distributed in a fibrillary background, where vacuoles were also
      noted. In the resected tumour scattered oligodendroglia-like cells were present.
      No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for
      synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP,
      IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic
      vacuoles in the neurons and in some neuronal processes. The seizures recurred in
      Case 1.Some clinicopathological features of this lesion suggest a possible
      relationship with dysembryoplastic neuroepithelial tumour (DNT) although the
      morphological features are not typical of DNT. Case 2 demonstrates that MVNT may
      remain asymptomatic. 

PMID- 24444359
TI  - An autopsy case of incipient Pick's disease: immunohistochemical profile of early
      stage Pick body formation.
AB  - There is little immunohistochemical information about the early stage of Pick
      body formation, due to the extremely limited opportunities of studying Pick's
      disease at the incipient or subclinical stage. We report a 62-year-old man
      without any clinical manifestations of Pick's disease, who died of B-cell
      lymphoma of the brainstem. Post mortem examination revealed many Pick bodies
      without obvious neuronal loss mainly in the left frontal and temporal lobes.
      Three brains of patients with typical Pick's disease (disease duration: 7, 11 and
      16 years) were also examined. Pick bodies were immunopositive for phosphorylated
      tau and 3-repeat tau, and less consistently for p62 in both incipient and typical
      cases. In the incipient case, borderline positivity for ubiquitin was evident in
      only a few Pick bodies, whereas in the typical cases many Pick bodies showed
      obvious positivity for ubiquitin. These findings suggest that Pick bodies are
      rarely ubiquitinated in the early stage of Pick body formation.

PMID- 24444360
TI  - Umbilical vein injection of misoprostol versus normal saline for the treatment of
      retained placenta: intrapartum placebo-controlled trial.
AB  - BACKGROUND: The third stage of labour may be complicated by retained placenta,
      which should be managed promptly because it may cause severe bleeding and
      infection, with a potentially fatal outcome. This study evaluated the
      effectiveness of umbilical vein injection of misoprostol for the treatment of
      retained placenta in a hospital setting. METHODS: This hospital-based placebo
      controlled trial was conducted at the Maternity Teaching Hospital, Erbil City,
      Kurdistan region, Northern Iraq from April 2011 to February 2012. The inclusion
      criteria were: gestational age of at least 28 weeks, vaginal delivery, and
      failure of the placenta to separate within 30 minutes after delivery of the
      infant despite active management of the third stage of labour. Forty-six women
      with retained placentas were eligible for inclusion. After informed consent was
      obtained, the women were alternately allocated to receive umbilical vein
      injection of either 800 mcg misoprostol dissolved in 20 mL of normal saline
      (misoprostol group) or 20 mL of normal saline only (saline group). The women were
      blinded to the group allocation, but the investigator who administered the
      injection was not. The trial was registered by the Research Ethics Committee of
      Hawler Medical University. RESULTS: After umbilical vein injection, delivery of
      the placenta occurred in 91.3% of women in the misoprostol group and 69.5% of
      women in the saline group, which was not a significant difference between the two
      groups. The median vaginal blood loss from the time of injection until delivery
      of the placenta was significantly less in the misoprostol group (100 mL) than in
      the saline group (210 mL) (p value < 0.001). CONCLUSION: Umbilical vein injection
      of misoprostol is an effective treatment for retained placenta, and reduces the
      volume of vaginal blood loss with few adverse effects. CLINICAL TRIAL
      REGISTRATION: Current Controlled Trial HMU: N252.1.2011.

PMID- 24444361
TI  - An L2 SUMO interacting motif is important for PML localization and infection of
      human papillomavirus type 16.
AB  - Human papillomaviruses (HPV) induce warts and cancers on skin and mucosa. The
      HPV16 capsid is composed of the proteins L1 and L2. After cell entry and virus
      disassembly, the L2 protein accompanies the viral DNA to promyelocytic leukaemia
      nuclear bodies (PML-NBs) within the host nuclei enabling viral transcription and
      replication. Multiple components of PML-NBs are regulated by small ubiquitin-like
      modifiers (SUMOs) either based on covalent SUMO modification (SUMOylation), or
      based on non-covalent SUMO interaction via SUMO interacting motifs (SIMs). We
      show here that the HPV16 L2 comprises at least one SIM, which is crucial for the
      L2 interaction with SUMO2 in immunoprecipitation and colocalization with SUMO2 in
      PML-NBs. Biophysical analysis confirmed a direct L2 interaction with SUMO
      substantiated by identification of potential L2-SUMO interaction structures in
      molecular dynamics simulations. Mutation of the SIM resulted in absence of the L2
      DNA complex at PML-NB and in a loss of infectivity of mutant HPV16 pseudoviruses.
      In contrast, we found that L2 SUMOylation has no effect on L2 localization in PML
      NBs and SUMO interaction. Our data suggest that the L2 SIM is important for L2
      interaction with SUMO and/or SUMOylated proteins, which is indispensable for the
      delivery of viral DNA to PML-NBs and efficient HPV infection.

PMID- 24444363
TI  - The VEGF- and PDGF-family of angiogenic markers have prognostic impact in soft
      tissue sarcomas arising in the extremities and trunk.
AB  - BACKGROUND: Soft-tissue sarcomas are rare malignant tumors of mesenchymal lineage
      that can arise in any part of the body. Prognosis, and hence also treatment may
      vary according to histologic subtype and localization. Angiogenesis is the
      process of forming new blood vessels from pre-existing ones. The deregulation of
      this process is thought to be an important step in malignant transformation. This
      study investigates the prognostic impact of platelet derived growth factor-
      (PDGF), vascular endothelial growth factor- (VEGF) and fibroblast growth factor
      (FGF) families in soft-tissue sarcomas of the extremities & trunk (ET) and
      visceral & retroperitoneal (VR) locations. METHODS: Tumor samples from 181
      patients (115 ET and 66 VR) with resected soft tissue sarcomas were collected and
      tissue microarrays were constructed. Immunohistochemistry was used to evaluate
      angiogenic marker expression. Recurrence-free survival (RFS), metastasis-free
      survival (MFS) and disease-specific survival (DSS) were used as endpoints in
      prognostic impact assessment. RESULTS: In univariate analyses, almost all
      investigated angiogenic markers had prognostic impact in the ET group. In
      contrast, only FGFR-1 showed any significant prognostic impact in the VR group.
      In the multivariate analyses, PDGF-D (HR = 1.863, 95% CI = 1.057-3.283, P =
      0.031), VEGFR-1 (HR = 2.106, 95% CI = 1.038-4.272, P = 0.039) and VEGF-A (HR
      2.095, 95% CI 1.028-4.271, P = 0.042) were independent negative prognosticators
      for DSS, MFS and RFS, respectively, in the ET group. FGFR-1 was an independent
      positive prognosticator for DSS (HR = 0.243, 95% CI = 0.095-0.618, P = 0.003) in
      the VR group. CONCLUSIONS: Angiogenic molecules from the PDGF and VEGF families
      have prognostic impact in soft-tissue sarcomas arising in the ET, but not in VR
      locations. In the latter histological grade and resection margins are the most
      important prognostic factors.

PMID- 24444364
TI  - Compensatory growth response and carcass quality after a period of lysine
      restriction in lean meat type barrows.
AB  - Because research indicates that responses on dietary restrictions may depend on
      the gender of pigs, we examined the interaction between the lysine level in
      different feeding periods and the performance and carcass quality of barrows in a
      2 * 2 factorial trial. In total 192 barrows were divided over 32 pens of six
      animals, and each pen was assigned to one of four dietary treatments: (1) high
      lysine levels in the growing (25-42 kg body weight [BW]), early finishing (42-73
      kg BW) and in the late finishing period (73-110 kg BW) (Group HH); (2) high
      lysine levels in the growing and early finishing period, and low lysine level in
      the late finishing period (Group HL); (3) low lysine levels in the growing and
      early finishing period, and high lysine level in the late finishing period (Group
      LH); and (4) low lysine levels in all periods (Group LL). To obtain the high
      lysine diets, L-lysine, as well as L-threonine, DL-methionine and L-tryptophan,
      were added to the low-lysine diets. The low-lysine diets contained 20% (in
      growing) or 30% (in finishing) lysine less than the high-lysine diets. Feeding
      Diet LH increased the daily gain and decreased the feed-to-gain ratio in the
      subsequent late finishing phase (p < 0.05). Between start and slaughter, Group LL
      showed lower daily gain and a higher feed-to-gain ratio than the three other
      groups (p < 0.05). Carcass yield and lean meat percentage depended on sufficient
      amino acid (AA) provision in the late finishing feed (p < 0.05). Lowering the AA
      concentrations in the diet decreased the amount of lysine needed per kg gain and
      per kg lean gain (p < 0.05). An interaction between AA levels in the different
      phases and lean gain was observed, with Group LL showing lower lean gain than the
      other three groups (p < 0.05). This study shows that strategic provision of a
      sufficient amount of AAs either in the growing and early finishing period or in
      the late finishing period largely counteracts the negative effects of AA
      restriction in other feeding phases. Barrows can show compensatory growth after a
      period of AA restriction. The results of the present study show that a sufficient
      level of lysine in the late finishing feed rather than in the growing and early
      finishing feed is important for obtaining good carcass quality. 

PMID- 24444362
TI  - MicroRNA-126 suppresses mesothelioma malignancy by targeting IRS1 and interfering
      with the mitochondrial function.
AB  - AIMS: MiR126 was found to be frequently lost in many types of cancer, including
      malignant mesothelioma (MM), which represents one of the most challenging
      neoplastic diseases. In this study, we investigated the potential tumor
      suppressor function of MiR126 in MM cells. The effect of MiR126 was examined in
      response to oxidative stress, aberrant mitochondrial function induced by
      inhibition of complex I, mitochondrial DNA (mtDNA) depletion, and hypoxia.
      RESULTS: MiR126 was up-regulated by oxidative stress in nonmalignant mesothelial
      (Met5A) and MM (H28) cell lines. In Met5A cells, rotenone inhibited MiR126
      expression, but mtDNA depletion and hypoxia up-regulated MiR126. However, these
      various stimuli suppressed the levels of MiR126 in H28 cells. MiR126 affected
      mitochondrial energy metabolism, reduced mitochondrial respiration, and promoted
      glycolysis in H28 cells. This metabolic shift, associated with insulin receptor
      substrate-1 (IRS1)-modulated ATP-citrate lyase deregulation, resulted in higher
      ATP and citrate production. These changes were linked to the down-regulation of
      IRS1 by ectopic MiR126, reducing Akt signaling and inhibiting cytosolic
      sequestration of Forkhead box O1 (FoxO1), which promoted the expression of genes
      involved in gluconeogenesis and oxidative stress defense. These metabolic changes
      induced hypoxia-inducible factor-1alpha (HIF1alpha) stabilization. Consequently,
      MiR126 suppressed the malignancy of MM cells in vitro, a notion corroborated by
      the failure of H28(MiR126) cells to form tumors in nude mice. INNOVATION AND
      CONCLUSION: MiR126 affects mitochondrial energy metabolism, resulting in MM tumor
      suppression. Since MM is a fatal neoplastic disease with a few therapeutic
      options, this finding is of potential translational importance.

PMID- 24444365
TI  - Non-invasive fetal sex determination by maternal plasma sequencing and
      application in X-linked disorder counseling.
AB  - OBJECTIVE: To develop a fetal sex determination method based on maternal plasma
      sequencing (MPS), assess its performance and potential use in X-linked disorder
      counseling. METHODS: 900 cases of MPS data from a previous study were reviewed,
      in which 100 and 800 cases were used as training and validation set,
      respectively. The percentage of uniquely mapped sequencing reads on Y chromosome
      was calculated and used to classify male and female cases. Eight pregnant women
      who are carriers of Duchenne muscular dystrophy (DMD) mutations were recruited,
      whose plasma were subjected to multiplex sequencing and fetal sex determination
      analysis. RESULTS: In the training set, a sensitivity of 96% and false positive
      rate of 0% for male cases detection were reached in our method. The blinded
      validation results showed 421 in 423 male cases and 374 in 377 female cases were
      successfully identified, revealing sensitivity and specificity of 99.53% and
      99.20% for fetal sex determination, at as early as 12 gestational weeks. Fetal
      sex for all eight DMD genetic counseling cases were correctly identified, which
      were confirmed by amniocentesis. CONCLUSIONS: Based on MPS, high accuracy of non
      invasive fetal sex determination can be achieved. This method can potentially be
      used for prenatal genetic counseling.

PMID- 24444366
TI  - Shared familial transmission of autism spectrum and attention
      deficit/hyperactivity disorders.
AB  - BACKGROUND: To determine whether familial transmission is shared between autism
      spectrum disorders and attention-deficit/hyperactivity disorder, we assessed the
      prevalence, rates of comorbidity, and familial transmission of both disorders in
      a large population-based sample of children during a recent 7 year period.
      METHODS: Study participants included all children born to parents with the Kaiser
      Permanente Northwest (KPNW) Health Plan between 1 January 1998 and 31 December
      2004 (n = 35,073). Children and mothers with physician-identified autism spectrum
      disorders (ASD) and/or attention-deficit/hyperactivity disorder (ADHD) were
      identified via electronic medical records maintained for all KPNW members.
      RESULTS: Among children aged 6-12 years, prevalence was 2.0% for ADHD and 0.8%
      for ASD; within those groups, 0.2% of the full sample (19% of the ASD sample and
      9.6% of the ADHD sample) had co-occurring ASD and ADHD, when all children were
      included. When mothers had a diagnosis of ADHD, first born offspring were at 6
      fold risk of ADHD alone (OR = 5.02, p < .0001) and at 2.5-fold risk of ASD alone
      (OR = 2.52, p < .01). Results were not accounted for by maternal age, child
      gestational age, child gender, and child race. CONCLUSIONS: Autism spectrum
      disorders shares familial transmission with ADHD. ADHD and ASD have a partially
      overlapping diathesis.

PMID- 24444367
TI  - A GMC oxidoreductase homologue is required for acetylation of glycopeptidolipid
      in Mycobacterium smegmatis.
AB  - The Mycobacterium tuberculosis Rv3409c gene is required for modulation of the
      Toll-like receptor 2 (TLR-2) signaling response in infected macrophages. Although
      each is annotated as encoding a cholesterol oxidase, neither Rv3409c nor its
      ortholog MSMEG1604 is required for the metabolism of cholesterol in mycobacteria.
      Here we report that a unique lipid, L1334, accumulates in a MSMEG1604 transposon
      mutant in the Mycobacterium smegmatis cell envelope. L1334 is a polar
      glycopeptidolipid that is hyperrhamnosylated and in which the 6-deoxytalose
      moiety is not acetylated. The alteration of L1334 acetylation is consistent with
      a reduced level of interference with TLR-2 signaling in mutant infected
      macrophages. 

PMID- 24444368
TI  - SeqBench: integrated solution for the management and analysis of exome sequencing
      data.
AB  - BACKGROUND: The rapid development of next generation sequencing technologies,
      including the recently introduced benchtop sequencers, made sequencing affordable
      for smaller research institutions. A widely applied method to identify causing
      mutations of diseases is exome sequencing, which proved to be cost-effective and
      time-saving. FINDINGS: SeqBench, a web-based application, combines management and
      analysis of exome sequencing data into one solution. It provides a user friendly
      data acquisition module to facilitate comprehensive and intuitive data handling.
      SeqBench provides direct access to the analysis pipeline SIMPLEX, which can be
      configured to run locally, on a cluster, or in the cloud. Identified genomic
      variants are presented along with several functional annotations and can be
      interpreted in a family context. CONCLUSIONS: The web-based application SeqBench
      supports the management and analysis of exome sequencing data, is open-source and
      available at http://www.icbi.at/SeqBench.

PMID- 24444369
TI  - Drug resistance in children at virological failure in a rural KwaZulu-Natal,
      South Africa, cohort.
AB  - BACKGROUND: Better understanding of drug resistance patterns in HIV-infected
      children on antiretroviral therapy (ART) is required to inform public health
      policies in high prevalence settings. The aim of this study was to characterise
      the acquired drug resistance in HIV-infected children failing first-line ART in a
      decentralised rural HIV programme. METHODS: Plasma samples were collected from
      101 paediatric patients (<=15 yrs of age) identified as failing ART. RNA was
      extracted from the plasma, reverse transcribed and a 1.3 kb region of the pol
      gene was amplified and sequenced using Sanger sequencing protocols. Sequences
      were edited in Geneious and drug resistance mutations were identified using the
      RegaDB and the Stanford resistance algorithms. The prevalence and frequency of
      mutations were analysed together with selected clinical and demographic data in
      STATA v11. RESULTS: A total of 101 children were enrolled and 89 (88%) were
      successfully genotyped; 73 on a non-nucleoside reverse-transcriptase inhibitor
      (NNRTI)-based regimen and 16 on a protease inhibitor (PI)-based regimen at the
      time of genotyping. The majority of patients on an NNRTI regimen (80%) had both
      nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutations.
      M184V and K103N were the most common mutations amongst children on NNRTI-based
      and M184V among children on PI-based regimens. 30.1% had one or more thymidine
      analogue mutation (TAM) and 6% had >=3 TAMs. Only one child on a PI-based regimen
      harboured a major PI resistance mutation. CONCLUSIONS: Whilst the patterns of
      resistance were largely predictable, the few complex resistance patterns seen
      with NNRTI-based regimens and the absence of major PI mutations in children
      failing PI-based regimens suggest the need for wider access to genotypic
      resistance testing in this setting.

PMID- 24444370
TI  - GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic
      gluconeogenesis in Type 2 diabetic mice.
AB  - GdCl3 (gadolinium chloride) has been shown to reduce blood glucose; however, the
      underlying mechanism remains unclear. Liver gluconeogenesis is an important
      pathway involved in the maintenance of glucose homoeostasis. The aim of the
      present study was to investigate the role of GdCl3 in hepatic gluconeogenesis and
      explore the precise molecular mechanism. Animals from a classical Type 2 diabetic
      mouse model, created by exposing C57BL/6J mice to a high-fat diet for 4 months,
      were treated with GdCl3 or saline. Body weight, blood glucose and insulin
      sensitivity were monitored. It was observed that GdCl3 significantly reduced
      blood glucose levels and improved insulin sensitivity. A pyruvate tolerance test
      showed further that GdCl3 suppressed gluconeogenesis in diabetic mice. In the
      livers of GdCl3-treated mice, the expression of Pepck (phosphoenolpyruvate
      carboxykinase) and G6pase (glucose-6-phosphatase), the key enzymes in
      gluconeogenesis, were dramatically reduced. Furthermore, experiments in
      hepatocarcinoma cells revealed that GdCl3 activated the Akt pathway to promote
      the phosphorylation of FoxO1 (forkhead box O1), leading to the suppression of
      gluconeogenesis by reducing the expression of PEPCK and G6Pase and resulting in
      decreased cellular production of glucose. Comparable results were observed in the
      livers of GdCl3-treated mice. In addition, we have shown that GdCl3 augmented the
      role of insulin to control hepatic glucose production. We conclude that GdCl3
      reduces hyperglycaemia via the Akt/FoxO1-induced suppression of hepatic
      gluconeogenesis, both in Type 2 diabetic mice (in vivo) and in hepatocarcinoma
      cells (in vitro), suggesting that GdCl3 may be a potential therapeutic agent for
      diabetes. 

PMID- 24444372
TI  - The care of older adults in hospital: if it's common sense why isn't it common
      practice?
AB  - AIMS AND OBJECTIVES: To present three converging myths that underlie the
      perception that nursing care for older persons in hospital is simple in
      comparison with its actual complexity. BACKGROUND: Literature provides strong
      evidence indicating that the myths we discuss inherently arise from ageism, the
      social value of older patients and the economic burden of being an older patient
      in hospital. These powerful social discourses promote harm to older patients.
      Harm emerges from both the omission of gerontological nursing knowledge and skill
      and the commission of acts that unintentionally harm. A corresponding ethical
      challenge results for acute care nurses. DESIGN: A discursive paper. METHODS: We
      illuminate gerontological issues by discussing three myths. In myth one, we
      detail four clusters of distinguishing characteristics in older hospitalised
      people. In the second myth, we challenge the idea that the role of the acute care
      hospital is to attend only to acute medical concerns. Finally, in the third myth,
      we address the issue of incorporating functional assessment into the acute care
      nursing assessment. We argue that functional assessment is poorly integrated and
      becomes acceptable only as long as the medical regimen is managed appropriately.
      CONCLUSION: Safe quality care in hospital for older adults requires a hybrid
      practice that integrates acute care specialty knowledge with gerontological
      nursing knowledge and skill. Clinical reasoning that integrates this type of
      nursing knowledge can prevent harm. RELEVANCE TO CLINICAL PRACTICE: Integrating
      key elements of acute care nursing specialty knowledge with gerontological
      nursing principles aids to prevent the omission of care that is known to be
      harmful to older people. Conversely, the commission of gerontologically sensitive
      acute care can enhance safety and promote quality care in hospital.

PMID- 24444373
TI  - Leriche operation for parotid gland pathology.

PMID- 24444371
TI  - Protection of neurons from high glucose-induced injury by deletion of MAD2B.
AB  - Diabetic encephalopathy may lead to cognitive deficits in diabetic patients and
      diminish quality of life. It has been shown that protracted hyperglycaemia is
      directly associated with neuronal apoptosis, which is involved in diabetic
      encephalopathy. The anaphase-promoting complex (APC) is essential for the
      survival of post-mitotic neurons. In our previous study, we found that the
      mitotic arrest deficient protein MAD2B, one of APC inhibitors, was expressed in
      neurons in central nervous system. However, whether MAD2B is involved in
      hyperglycaemia-induced apoptosis and thus takes part in diabetic encephalopathy
      is still unknown. To address this issue, we first explored the expression of
      MAD2B and cyclin B1 detected by immunofluorescence and Western blot. It was found
      that hyperglycaemia remarkably increased the expression of MAD2B and accumulation
      of cyclin B1 in cortices of diabetes mellitus rat model and in cultured primary
      neurons. To further explore the role of MAD2B in hyperglycaemia-induced neuronal
      injury, we depleted MAD2B expression by a specifically targeted shRNA against
      MAD2B. We observed that MAD2B deficiency alleviated cyclin B1 expression and
      apoptotic neuronal death. These results demonstrate that MAD2B expression is the
      main culprit for accumulation of cyclin B1 and apoptosis in neurons under high
      glucose. Moreover, inhibition of the expression of MAD2B prevented neurons from
      entering an aberrant S phase that led differentiated neurons into apoptotic cell
      death. These results suggest that hyperglycaemia induced neuronal apoptosis
      through inducing expression of MAD2B, which represents a novel mechanism of
      diabetic encephalopathy. 

PMID- 24444375
TI  - Bunina bodies in motor and non-motor neurons revisited: a pathological study of
      an ALS patient after long-term survival on a respirator.
AB  - Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs)
      found in the remaining lower motor neurons (LMNs) of patients with sporadic
      amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular
      pathology. We examined a case of SALS, unassociated with TDP-43 or C9ORF72
      mutation, of 12 years duration in a 75-year-old man, who had received artificial
      respiratory support for 9 years, and showed widespread multisystem degeneration
      with TDP-43 pathology. Interestingly, in this patient, many NCIs reminiscent of
      BBs were observed in the oculomotor nucleus, medullary reticular formation and
      cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not
      been previously described, we performed ultrastructural and immunohistochemical
      studies of these NCIs to gain further insight into the nature of BBs. In each
      region, the ultrastructural features of these NCIs were shown to be identical to
      those of BBs previously described in LMNs. These three regions and the relatively
      well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were
      immunostained with antibodies against cystatin C (CC) and TDP-43. Importantly, it
      was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs,
      but not of non-motor neurons, and that in the cerebellar dentate nucleus, the
      ratio of neurons with BBs and TDP-43 inclusions/neurons with BBs was
      significantly lower than in other regions. These findings suggest that the
      occurrence of BBs with CC immunoreactivity is intrinsically associated with the
      particular cellular properties of LMNs, and that the mechanism responsible for
      the formation of BBs is distinct from that for TDP-43 inclusions.

PMID- 24444374
TI  - YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and
      antioxidant enzymes.
AB  - AIMS: Acquisition and detoxification of metal ions are vital biological
      processes. Given the requirement of metallochaperones in cellular copper
      distribution and metallation of cuproproteins, this study investigates whether
      the metallochaperones also deliver metal ions for transporters functioning in
      metal detoxification. RESULTS: Resistance to excess cadmium and copper of the
      yeast Saccharomyces cerevisiae, which is conferred by PCA1 and CaCRP1 metal
      efflux P-type ATPases, respectively, does not rely on known metallochaperones,
      Atx1p, Ccs1p, and Cox17p. Copper deficiency induced by the expression of CaCRP1
      encoding a copper exporter occurs in the absence of Atx1p. Intriguingly, CCS1
      encoding the copper chaperone for superoxide dismutase 1 (Sod1p) is necessary for
      cadmium resistance that is mediated by Ycf1p, a vacuolar cadmium sequestration
      transporter. This is attributed to Ccs1p's role in the maturation of Sod1p rather
      than its direct interaction with Ycf1p for cadmium transfer. Functional defect in
      Ycf1p associated with the absence of Sod1p as well as another antioxidant enzyme
      Glr1p is rescued by anaerobic growth or substitutions of specific cysteine
      residues of Ycf1p to alanine or serine. This further supports oxidative
      inactivation of Ycf1p in the absence of Ccs1p, Sod1p, or Glr1p. INNOVATION: These
      results provide new insights into the mechanisms of metal metabolism, interaction
      among metal ions, and the roles for antioxidant systems in metal detoxification.
      CONCLUSION: Copper metabolism and antioxidant enzymes maintain the function of
      Ycf1p for cadmium defense.

PMID- 24444376
TI  - Estimating SIT-driven population reduction in the Mediterranean fruit fly,
      Ceratitis capitata, from sterile mating.
AB  - Area-wide sterile insect technique (SIT) programs assume that offspring reduction
      of the target population correlates with the mating success of the sterile males
      released. However, there is a lack of monitoring tools to prove the success of
      these programs in real-time. Field-cage tests were conducted under the
      environmental conditions of the Mediterranean coast of Spain to estimate: (a) the
      mating success of sterile Vienna-8 (V8) Ceratitis capitata males using molecular
      markers and (b) their efficacy to reduce C. capitata populations under six
      release ratios of wild females to wild males to V8 males (1:0:0, 1:1:0, 1:1:1,
      1:1:5, 1:1:10, and 1:1:20). Statistical models were developed to predict: (a) the
      number of females captured in traps, (b) sperm ID (sterile or not) in
      spermathecae of the trapped females, and (c) the viable offspring produced, using
      release ratio and temperature as predictors. The number of females captured was
      affected by relative humidity. However, its influence in the model was low.
      Female captures were significantly higher in ratios 1:0:0 compared to ratios
      where V8 males were released. The proportion of V8 sperm in spermathecae
      increased with temperature and with the number of V8 males released, but leveled
      off between ratios 1:1:10 and 1:1:20. In all seasons, except winter (no
      offspring), viable offspring increased with temperature and was lowest for ratio
      1:1:20. For the first time, a strong negative relationship between proportion of
      V8 sperm detected by molecular tools and C. capitata offspring was established.
      The models obtained should contribute to enhance the efficacy of SIT programs
      against this pest. 

PMID- 24444377
TI  - Electronic waste - an emerging threat to the environment of urban India.
AB  - Electronic waste or e-waste is one of the emerging problems in developed and
      developing countries worldwide. It comprises of a multitude of components with
      valuable materials, some containing toxic substances, that can have an adverse
      impact on human health and the environment. Previous studies show that India has
      generated 0.4 million tons of e-waste in 2010 which may increase to 0.5 to 0.6
      million tons by 2013-2014. Coupled with lack of appropriate infrastructural
      facilities and procedures for its disposal and recycling have posed significant
      importance for e-waste management in India. In general, e-waste is generated
      through recycling of e-waste and also from dumping of these wastes from other
      countries. More of these wastes are ending up in dumping yards and recycling
      centers, posing a new challenge to the environment and policy makers as well. In
      general electronic gadgets are meant to make our lives happier and simpler, but
      the toxicity it contains, their disposal and recycling becomes a health
      nightmare. Most of the users are unaware of the potential negative impact of
      rapidly increasing use of computers, monitors, and televisions. This review
      article provides a concise overview of India's current e-waste scenario, namely
      magnitude of the problem, environmental and health hazards, current disposal,
      recycling operations and mechanisms to improve the condition for better
      environment. 

PMID- 24444378
TI  - A comparative study of two various models of organising diabetes follow-up in
      public primary health care - the model influences the use of services, their
      quality and costs.
AB  - BACKGROUND: In Finland diabetologists have long been concerned about the level of
      diabetes care as the incidence of type 1 diabetes and complicated type 2 diabetes
      is exceeding the capacity of specialist clinics. We compared the outcome of
      diabetes care in two middle-sized Finnish municipalities with different models of
      diabetes care organisation in public primary health care. In Kouvola the primary
      health care of all diabetic patients is based on general practitioners, whereas
      in Nurmijarvi the follow-up of type 1 and most complicated type 2 diabetic
      patients is assigned to a general practitioner specialised in diabetes care.
      METHODS: Our study population consisted of all adult diabetic patients living in
      the municipalities under review.We compared the use and costs of public diabetes
      care, glycemic control, blood pressure, LDL-cholesterol level, the application of
      the national guidelines and patient satisfaction. The main outcome measures were
      the costs and use of health care services due to diabetes and its complications.
      RESULTS: In Nurmijarvi, where diabetes care was centralised, more type 1 diabetic
      patients were followed up in primary health care than in Kouvola, where general
      practitioners need more specialist consultations. The centralisation resulted in
      cost savings in the diabetes care of type 1 diabetic patients. Although the
      quality of care was similar, type 1 diabetic patients were more satisfied with
      their follow-up in the centralised system. In the care of type 2 diabetic
      patients the centralised system required fewer specialist consultations, but the
      quality and costs were similar in both models. CONCLUSIONS: The follow-up of most
      diabetic patients - including type 1 diabetes - can be organised in primary
      health care with the same quality as in secondary care units. The centralised
      primary care of type 1 diabetes is less costly and requires fewer specialist
      consultations.

PMID- 24444379
TI  - Directly Observed Treatment Short-course (DOTS) for tuberculosis control program
      in Gambella Regional State, Ethiopia: ten years experience.
AB  - BACKGROUND: Tuberculosis is still the leading cause of illness in the world which
      accounted for 2.5% of the global burden of disease, and 25% of all avoidable
      deaths in developing countries. The aim of study was to assess impact of DOTS
      strategy on tuberculosis case finding and treatment outcome in Gambella Regional
      State, Ethiopia from 2003 up to 2012 and from 2002 up to 2011, respectively.
      METHODS: Health facility-based retrospective study was conducted. Data were
      collected and reported in quarterly basis using WHO reporting format for TB case
      finding and treatment outcome from all DOTS implementing health facilities in all
      zones of the region to Federal Ministry of Health. RESULTS: A total of 10024 all
      form of TB cases had been registered between the periods from 2003 up to 2012. Of
      them, 4100 (40.9%) were smear-positive pulmonary TB, 3164 (31.6%) were smear
      negative pulmonary TB and 2760(27.5%) had extra-pulmonary TB. Case detection rate
      of smear-positive pulmonary TB had increased from 31.7% to 46.5% from the total
      TB cases and treatment success rate increased from 13% to 92% with average mean
      value of being 40.9% (SD = 0.1) and 55.7% (SD = 0.28), respectively for the
      specified year periods. Moreover, the average values of treatment defaulter and
      treatment failure rates were 4.2% and 0.3%, respectively. CONCLUSION: It is
      possible to achieve the recommended WHO target which is 70% of CDR for smear
      positive pulmonary TB, and 85% of TSR as it was already been fulfilled the
      targets for treatments more than 85% from 2009 up to 2011 in the region. However,
      it requires strong efforts to enhance case detection rate of 40.9% for smear
      positive pulmonary TB through implementing alternative case finding strategies.

PMID- 24444381
TI  - Functioning of long-term survivors of first-ever intracerebral hemorrhage.
AB  - OBJECTIVES: There are few data on long-term functional outcome after
      intracerebral hemorrhage (ICH). We aimed to assess functional dependency and
      cognitive impairment in long-term survivors of first-ever intracerebral
      hemorrhage. MATERIALS AND METHODS: Between August and November 2011, we contacted
      all survivors from a cohort of 134 consecutive patients hospitalized with a first
      ever ICH in the period 2005-2009 in a well-defined catchment area. We did an
      extensive face-to-face follow-up including the National Institute of Health
      Stroke Scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI),
      and the Montreal Cognitive Assessment (MoCA). RESULTS: Fifty-one patients (38%)
      were alive. Fifty agreed to take part in the follow-up. The median follow-up time
      was 3.8 years. Thirty-four patients (68%) were independent (mRS 0-2) and 16 (32%)
      dependent (mRS 3-5). Factors independently associated with dependency were
      leukoaraiosis score (OR 2.3 per increasing point, P = 0.003) and female sex (OR
      5.1, P = 0.038). Twenty-seven patients (61%) had cognitive impairment (MoCA <=
      23). Factors independently associated with cognitive impairment were age (OR 2.4
      per 10 years, P = 0.010) and lobar ICH location (OR 14.1, P = 0.016).
      CONCLUSIONS: A large proportion of long-term survivors of ICH in Southern Norway
      live functionally independent lives in their private homes. Dependency is linked
      to leukoaraiosis and female sex. Cognitive impairment is common and linked to
      lobar location of ICH.

PMID- 24444382
TI  - Development of a brief questionnaire (ICQ-S) to monitor inhaled corticosteroid
      side-effects in clinical practice.
AB  - BACKGROUND: Side-effect concerns impede adherence with inhaled corticosteroids
      (ICS) and often underlie poor asthma control. We developed a brief version (ICQ
      S) of the 57-item Inhaled Corticosteroids side-effect Questionnaire (ICQ) to
      facilitate side-effect monitoring in busy clinics. METHODS: Part 1: After
      completion by 482 patients with doctor-diagnosed asthma, each ICQ item underwent
      item reduction analysis. Part 2: Patients prescribed ICS for asthma completed the
      ICQ at baseline (BL), ICQ-S at day 14 (D14) and day 28 (D28), and 6-item Asthma
      Control Questionnaire (ACQ) and Mini Asthma Quality of Life Questionnaire
      (MiniAQLQ) at BL, D14 and D28. 14-day test-retest reliability was assessed by
      intraclass correlation coefficient (ICC) between ICQ-S scores and internal
      consistency by Cronbach's alpha (alpha) coefficient and item-total correlations
      of ICQ-S. Criterion validity was assessed by correlations (Spearman's rho)
      between ICQ and ICQ-S total score. Patients reported duration and difficulty of
      ICQ-S completion at D28. RESULTS: Part 1: The ICQ-S consists of fifteen
      local/systemic ICS side-effects of similar range to the full ICQ. Part 2: 62
      asthma patients (mean ACQ score 0.79 +/- SD 0.83) prescribed daily ICS [BDP
      equivalent median dose 1000 MUg (IQR: 500, 1000)] participated. ICC between ICQ-S
      scores was 0.90. All item-total correlations were rho >= 0.20. The ICQ-S
      demonstrated criterion validity, for example, ICQ and ICQ-S were strongly
      associated (rho = 0.86). 81% of patients completed the ICQ-S within 5 minutes and
      97% found completion 'not difficult'. CONCLUSION: The ICQ-S is a brief, patient
      friendly tool with good reliability and validity, which may be useful for
      monitoring ICS side-effects in clinical practice.

PMID- 24444384
TI  - Near-hanging and its management in the acute inpatient mental health setting.
AB  - Being admitted to an inpatient mental health unit does not necessarily protect a
      patient against suicidal behavior. Given their purpose and design, these clinical
      areas can provide a safe environment for reducing hanging deaths. Strategies for
      reducing suicide by hanging in acute inpatient units should include ongoing
      review of the safety of the environment and the emergency management of near
      hanging. After receiving a request from inpatient nursing staff to develop an
      education program focused on the emergency management of near-hanging, the
      authors undertook a review of the literature to (a) identify the evidence base
      within this area and (b) establish an effective means to promote safe practice
      with the staff. This article provides a synthesis of the literature review and
      its implications for nursing practice. [Journal of Psychosocial Nursing and
      Mental Health Services, 52(5), 41-45.]. 

PMID- 24444385
TI  - Characteristics of temper tantrums in preschoolers with disruptive behavior in a
      clinical setting.
AB  - The purpose of this study was to describe clinician-observed, naturally occurring
      temper tantrums in preschoolers ages 2 to 5.5 diagnosed with severe behavior
      problems. Participants were 24 mother-child dyads enrolled in an intensive
      outpatient treatment program. Clinicians timed and observed 330 temper tantrums,
      rated their intensity, and recorded occurrence of 16 behaviors, tantrum
      precipitants, and interventions; parents completed the Achenbach Child Behavior
      Checklist pre- and posttreatment. Data were analyzed using descriptive
      statistics, Pearson chi square, paired t tests, and generalized linear modeling.
      Mean tantrum duration was 3.4 minutes (range = 0.2 to 26.5 minutes); most
      tantrums were low in intensity. Noncompliance precipitated 52% of tantrums.
      Aggressive behaviors were more likely to occur early in tantrums, with distress
      behaviors occurring later. Parent surveys indicated perceptions of behavioral
      improvement but no change in tantrum behavior. Study findings corroborate those
      of previous studies using retrospective parent reports.

PMID- 24444383
TI  - Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively
      lethal to MYC-dependent human breast cancer cells.
AB  - BACKGROUND: Although MYC is an attractive therapeutic target for breast cancer
      treatment, it has proven challenging to inhibit MYC directly, and clinically
      effective pharmaceutical agents targeting MYC are not yet available. An
      alternative approach is to identify genes that are synthetically lethal in MYC
      dependent cancer. Recent studies have identified several cell cycle kinases as
      MYC synthetic-lethal genes. We therefore investigated the therapeutic potential
      of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast cancer.
      METHODS: Using small interfering RNA (siRNA), MYC expression was depleted in 26
      human breast cancer cell lines and cell proliferation evaluated by BrdU
      incorporation. MYC-dependent and MYC-independent cell lines were classified based
      on their sensitivity to siRNA-mediated MYC knockdown. We then inhibited CDKs
      including CDK4/6, CDK2 and CDK1 individually using either RNAi or small molecule
      inhibitors, and compared sensitivity to CDK inhibition with MYC dependence in
      breast cancer cells. RESULTS: Breast cancer cells displayed a wide range of
      sensitivity to siRNA-mediated MYC knockdown. The sensitivity was correlated with
      MYC protein expression and MYC phosphorylation level. Sensitivity to siRNA
      mediated MYC knockdown did not parallel sensitivity to the CDK4/6 inhibitor
      PD0332991; instead MYC-independent cell lines were generally sensitive to
      PD0332991. Cell cycle arrest induced by MYC knockdown was accompanied by a
      decrease in CDK2 activity, but inactivation of CDK2 did not selectively affect
      the viability of MYC-dependent breast cancer cells. In contrast, CDK1
      inactivation significantly induced apoptosis and reduced viability of MYC
      dependent cells but not MYC- independent cells. This selective induction of
      apoptosis by CDK1 inhibitors was associated with up-regulation of the pro
      apoptotic molecule BIM and was p53-independent. CONCLUSIONS: Overall, these
      results suggest that further investigation of CDK1 inhibition as a potential
      therapy for MYC-dependent breast cancer is warranted.

PMID- 24444386
TI  - Disruptive mood dysregulation disorder: a new diagnosis in the DSM-5.
AB  - This article explores a new diagnosis in the Diagnostic and Statistical Manual of
      Mental Disorders (5th ed.)-disruptive mood dysregulation disorder (DMDD).
      Frequent comorbidities of DMDD include oppositional defiant disorder and
      attention-deficit/hyperactivity disorder. The evolution of DMDD and how this
      diagnostic category may remedy an overdiagnosis of pediatric bipolar disorder are
      discussed.

PMID- 24444387
TI  - Graves' disease shows a significant increase in the Helicobacter pylori
      recurrence.

PMID- 24444388
TI  - NOD1 and NOD2 expression and function in very preterm infant mononuclear cells.
AB  - AIM: To evaluate mononuclear cell expression and function of the cytosolic
      nucleotide-binding oligomerization domain-containing receptors, NOD1 and NOD2, in
      very preterm and full-term infants. METHODS: NOD1 and NOD2 gene and protein
      expression in very preterm infants, term infants and healthy adult, cord and
      peripheral blood mononuclear cells (C/PBMC) were quantified using qPCR and flow
      cytometry. Cytokine responses of purified infant and adult monocytes to NOD1- and
      NOD2-specific agonists were assessed using a multiplex immunoassay (Bioplex).
      RESULTS: NOD1 and NOD2 were expressed by a range of infant and adult mononuclear
      cell types, including T- and B cells, with highest expression in classical
      (CD14(++) CD16(-) ) and intermediate (CD14(++) CD16(+) ) monocytes. NOD1 and NOD2
      expression levels by monocytes from very preterm infant were similar to those in
      term infants or adults. Monocyte production of TNFalpha, IL-6 and IL-1beta?
      induced by activation of NOD1 and NOD2 was similar between very preterm infants,
      term infants and adults. CONCLUSION: Monocyte expression and function of NOD1 and
      NOD2 in very preterm infants are intact and comparable/equivalent to term infants
      and adults. Functional deficiencies in monocyte NOD signalling pathways are
      unlikely to contribute to the increased susceptibility to bacterial sepsis in
      preterm infants.

PMID- 24444389
TI  - A bovine viral diarrhea virus type 1a strain in China: isolation, identification,
      and experimental infection in calves.
AB  - BACKGROUND: Bovine viral diarrhea virus (BVDV) is one of the most important
      pathogens in cattle. Previously, BVDV sub-genotypes of 1b, 1c, 1d, and 1 m were
      detected in China. However, isolation of BVDV type 1a from cattle has not been
      reported in China. In 2010, twenty nasal swabs and blood samples were collected
      from the cattle suspected BVDV infection in Henan province, China. A BVDV isolate
      was isolated using cell culture, and the pathogenesis of the virus isolate was
      studied. METHODS: Virus isolation was performed on MDBK cells. The virus
      identification was conducted by RT-PCR, neutralization test and
      immunofluorescence assay. In order to determine the genotype of the newly
      isolated virus, the 5' un-translated region (5'UTR) of the virus isolate was
      cloned, sequenced and phylogenetically analyzed. To evaluate the virulence of the
      virus isolate, four BVDV sero-negative calves were intranasally inoculated with
      the virus suspension. Rectal temperatures and clinical signs were recorded daily.
      Blood samples were analyzed for changes in white blood cell counts, and tissue
      samples were taken for histopathology analysis. RESULTS: A new isolate of bovine
      viral diarrhea virus (BVDV), named HN01, was isolated from the nasal swabs using
      MDBK cell culture. The HN01 strain caused cytopathic effect (CPE) in MDBK cell
      cultures after two passages. The virus specifically reacted to BVDV1-specific
      monoclonal antibody in an immunofluorescence assay. A fragment of 288 bp of
      genome from this isolate was amplified by the RT-PCR. Phylogenetic analysis of
      5'UTR indicated that the virus was BVDV 1a. In the pathogenesis study, four
      calves experimentally infected with the BVDV strain developed depression, cough
      and other clinical signs. Calves showed high temperature over 40 degrees C, and
      white blood cell counts dropped more than 40%. CONCLUSIONS: A new subgenotype 1a
      strain of BVDV was firstly isolated from dairy cattle in China. The experimental
      infection showed that the virus was moderate pathogenic to cattle and can be used
      as a BVDV challenge virus to evaluate the efficacy of BVDV vaccines in the target
      animals.

PMID- 24444390
TI  - Sublingual or subcutaneous immunotherapy for seasonal allergic rhinitis: an
      indirect analysis of efficacy, safety and cost.
AB  - RATIONALE, AIMS AND OBJECTIVES: The standard of preventive care for poorly
      controlled seasonal allergic rhinitis (AR) is subcutaneous immunotherapy (SCIT)
      with allergen extracts, administered in a physician's office. As an alternative
      to SCIT, sublingual immunotherapy (SLIT) is now an option for patients with
      seasonal AR. Oralair, a SLIT tablet containing freeze-dried allergen extracts of
      five grasses [cocksfoot (Dactylis glomerata), meadow grass (Poa pratensis), rye
      grass (Lolium perenne), sweet vernal grass (Anthoxanthum odoratum) and timothy
      grass (Phleum pratense)], and Grazax, a SLIT tablet containing a standardized
      extract of grass pollen allergen from timothy grass (P pratenase), are two such
      agents currently available in many countries. However, head-to-head comparative
      data are not available. In this study, an indirect comparison on efficacy, safety
      and cost was undertaken between Oralair, Grazax and SCIT. METHODS: A systematic
      review was conducted for double-blind placebo-controlled randomized trials
      evaluating Oralair, Grazax or SCIT in patients with grass-induced seasonal AR.
      Using placebo as the common control, an indirect statistical comparison between
      treatments was performed using meta regression analysis with active drug as the
      primary independent variable. An economic analysis, which included both direct
      and indirect costs for the Canadian setting, was also undertaken. RESULTS:
      Overall, 20 placebo-controlled trials met the study inclusion criteria. The
      indirect analysis suggested improved efficacy with Oralair over SCIT
      [standardized mean difference (SMD) in AR symptom control = -0.21; P = 0.007] and
      Grazax (SMD = -0.18; P = 0.018). In addition, there were no significant
      differences in the risk of discontinuation due to adverse events between
      therapies. Oralair was associated with cost savings against year-round SCIT
      ($2471), seasonal SCIT ($948) and Grazax ($1168) during the first year of
      therapy. CONCLUSIONS: Oralair has at least non-inferior efficacy and comparable
      safety against SCIT and Grazax at a lower annual cost.

PMID- 24444391
TI  - Epigallocatechin-3-gallate modulates anti-oxidant defense enzyme expression in
      murine submandibular and pancreatic exocrine gland cells and human HSG cells.
AB  - Sjogren's syndrome (SS) and type-1 diabetes are prevalent autoimmune diseases in
      the USA. We reported previously that epigallocatechin-3-gallate (EGCG) prevented
      and delayed the onset of autoimmune disease in non-obese diabetic (NOD) mice, a
      model for both SS and type-1 diabetes. EGCG also normalized the levels of
      proteins related to DNA repair and anti-oxidant activity in NOD.B10.Sn-H2 mice, a
      model for primary SS, prior to disease onset. The current study examined the
      effect of EGCG on the expression of anti-oxidant enzymes in the submandibular
      salivary gland and the pancreas of NOD mice and cultured human salivary gland
      acinar cells. NOD mice consuming 0.2% EGCG daily dissolved in water showed higher
      protein levels of peroxiredoxin 6 (PRDX6), a major anti-oxidant defense protein,
      and catalase, while the untreated NOD mice exhibited significantly lowered levels
      of PRDX6. Similarly, pancreas samples from water-fed NOD mice were depleted in
      PRDX6 and superoxide dismutase, while EGCG-fed mice showed high levels of these
      anti-oxidant enzymes. In cultured HSG cells EGCG increased PRDX6 levels
      significantly, and this was inhibited by p38 and JNK inhibitors, suggesting that
      the EGCG-mediated increase in protective anti-oxidant capacity is regulated in
      part through mitogen-activated protein kinase pathway signaling. This mechanism
      may explain the higher levels of PRDX6 found in EGCG-fed NOD mice. These
      preclinical observations warrant future preclinical and clinical studies to
      determine whether EGCG or green tea polyphenols could be used in novel preventive
      and therapeutic approaches against autoimmune diseases and salivary dysfunction
      involving oxidative stress.

PMID- 24444392
TI  - Identification of ractopamine glucuronides and determination of bioactive
      ractopamine residues and its metabolites in food animal urine by ELISA, LC-MS/MS
      and GC-MS.
AB  - Ractopamine glucuronides have been identified in cattle urine sampled by LC
      MS/MS. An ELISA method, which was capable of specifically determining (1R, 3R)
      ractopamine stereoisomer and its glucuronide metabolites, had more than 100%
      recovery with an acceptable coefficient of variation in the inter- and intra
      assay variation tests for RR-ractopamine. The concentration levels of parent
      ractopamine and ractopamine glucuronide metabolites as the main components of
      total ractopamine in cattle and sheep urine showed similar depletion trends, in
      which the concentration curves increased and reached a climax during the feeding
      period, and then dropped quickly when entering the withdrawal period. Data from
      the three methods had very good pair-wise correlations. In the cattle urine
      samples, the correlation coefficient (R(2)) for parent ractopamine between the
      ELISA and the LC-MS/MS or GC-MS results were 0.93 or 0.92; R(2) values for parent
      ractopamine and total ractopamine data measured by LC-MS/MS and GC-MS were 0.9651
      and 0.9677, respectively. All R(2) values for data gained from sheep urine
      samples were >0.95. The study indicated that the close levels of RR-ractopamine
      stereoisomer in cattle and sheep urine samples may imply the presence of a
      similar depletion pattern in other livestock, and thus would facilitate an
      accurate detection and management of ractopamine usage in food safety. 

PMID- 24444393
TI  - Quantitative risk-benefit analysis of fish consumption for women of child-bearing
      age in Hong Kong.
AB  - Maternal fish consumption is associated with both risks from methylmercury (MeHg)
      and beneficial effects from omega-3 fatty acids to the developing foetal brain.
      This paper assessed the dietary exposure to MeHg of women of child-bearing age
      (20-49 years) in Hong Kong, and conducted risk-benefit analysis in terms of the
      effects in children's intelligent quotient (IQ) based on local data and the
      quantitative method derived by the expert consultation of FAO/WHO. Results showed
      that average and high consumers consume 450 and 1500 g of fish (including
      seafood) per week, respectively. About 11% of women of child-bearing age had a
      dietary exposure to MeHg exceeding the PTWI of 1.6 ug kg(-1) bw. In pregnant
      women MeHg intake may pose health risks to the developing foetuses. For average
      consumers, eating any of the 19 types of the most commonly consumed fish and
      seafood during pregnancy would result in 0.79-5.7 IQ points gain by their
      children. For high consumers, if they only ate tuna during pregnancy, it would
      cause 2.3 IQ points reduction in their children. The results indicated that for
      pregnant women the benefit outweighed the risk associated with eating fish if
      they consume different varieties of fish in moderation.

PMID- 24444394
TI  - Method for assessing lead, cadmium, mercury and arsenic in high-density
      polyethylene packaging and study of the migration into yoghurt and simulant.
AB  - The purpose of this paper was to assess the concentration of lead (Pb), cadmium
      (Cd), mercury (Hg) and arsenic (As) in high-density polyethylene (HDPE) packaging
      intended for contact with yoghurt and the migration of these elements using the
      food itself and 3% acetic acid as a food simulant in accordance to ANVISA, the
      Brazilian Health Surveillance Agency. In order to perform this study, it was
      necessary to develop and validate a method by inductively coupled plasma optical
      emission spectroscopy (ICP-OES) analysis. For method validation, the parameters
      linearity, limits of detection (LODs) and quantification (LOQs), accuracy and
      precision were determined. Fifteen commercial samples of yoghurt, marketed in
      Campinas - Sao Paulo (Brazil), were used for the analysis. The packaging and
      yoghurt were digested in high-pressure ashing equipment (HPA) and the migration
      of the elements into simulant were determined directly in the solution. The
      validated method proved adequate and the results obtained showed that all the
      packaging had levels of Hg and Cd below the LOQ, corresponding to 1.0 and 1.5 MUg
      l(-1), respectively. The highest levels of As and Pb were 0.87 and 462.3 mg kg(
      1), respectively. The migration of these elements to the yoghurt after 45 days of
      contact at 4oC was below the LOQ for all the samples assessed. The results of
      specific migration into 3% acetic acid simulant showed the concentrations of Cd,
      Hg and As below 5, 5 and 10 ug kg(-1), respectively, which are the maximum limits
      set by ANVISA. However, for three samples the packaging lid showed migration of
      Pb into simulant ranging from 30.6 to 40.2 MUg kg(-1), exceeding the limit set by
      ANVISA of 10 MUg kg(-1).

PMID- 24444395
TI  - Differences in the knowledge and compliance with secondary prevention of stroke
      between transient ischaemic attack patients with and without subsequent stroke.
AB  - AIMS AND OBJECTIVES: To evaluate the differences in the knowledge and compliance
      with secondary prevention of stroke between transient ischaemic attack patients
      with and without subsequent stroke. BACKGROUND: No previous study has
      demonstrated whether there are differences in the knowledge and compliance with
      secondary prevention of stroke between transient ischaemic attack patients with
      and without subsequent stroke. If there are differences, the health education
      regarding the stroke knowledge should be conducted separately and differently for
      the two groups. METHODS AND DESIGN: We consecutively recruited 355 transient
      ischaemic attack patients with/without subsequent stroke from our hospital from 1
      December 2008-31 December 2011. There were 304 patients receiving health
      education both upon hospital discharge and 90 days after discharge. Through
      telephone interviews, six months after discharge, only 180 patients completed the
      survey to determine in detail their general knowledge and compliance with
      secondary prevention of stroke. RESULTS: The transient ischaemic attack patients
      with subsequent stroke exhibited a higher identification rate of speech disorder,
      weakness and decreased sensation or inability to feel things, compared with those
      without subsequent stroke (76.1 vs. 66.3%, p < 0.05; 91.5 vs. 73.5%, p < 0.05;
      62.2 vs. 46.9%, p < 0.05). The compliance rates to antiplatelet agents and
      statins therapy were higher in transient ischaemic attack patients with
      subsequent stroke compared with those without subsequent stroke (80.5 vs. 65.3%,
      p < 0.05; 53.7 vs. 35.7%, p < 0.05). CONCLUSIONS: The transient ischaemic attack
      patients with subsequent stroke exhibit a higher identification rate of most of
      the warning signs of stroke and a better compliance with antiplatelet agents and
      statins therapy of stroke compared with those without subsequent stroke. Thus, we
      suggest that transient ischaemic attack patients should receive additional health
      education to increase their awareness of the harms of stroke. RELEVANCE TO
      CLINICAL PRACTICE: Clinicians should be aware of conducting different health
      education to patients with transient ischaemic attack and stroke. Also, it is
      important to give health education to individualised patients based on their
      actual risk of stroke.

PMID- 24444396
TI  - Left ventricular hypertrophy among black hypertensive patients: focusing on the
      efficacy of angiotensin converting enzyme inhibitors.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is an independent cardiovascular
      risk factor in patients with essential hypertension. The main objective of this
      study was to assess the echocardiographic prevalence of left ventricular
      hypertrophy in patients with hypertension, its risk factors and effect of
      antihypertensive drugs on its prevalence. METHODS: A hospital based cross
      sectional study was conducted on 200 hypertensive patients on treatment in
      southwest Ethiopia. A pretested structured questionnaire was used to collect data
      from participants and their clinical records. Blood pressure and anthropometric
      measurements were taken according to recommended standards. Left ventricular mass
      was measured by transthoracic echocardiography. Associations between categorical
      variables were assessed using chi-square test and odds ratio with 95% confidence
      interval. Logistic regression model was done to identify risks factors of LVH. P
      values of < 0.05 were considered as statistically significant. RESULTS: The mean
      age, systolic blood pressure, diastolic blood pressure and body mass index were
      55.7 +/- 11.3 years, 139.2 +/- 7.7 mmHg, 89.2 +/- 5.7 mmHg and 24.2 +/- 3.4 Kg/m2
      respectively. The overall prevalence of LVH among these study subjects was 52%.
      Age >=50 years (OR: 3.49, 95% CI 1.33-9.14, P = 0.011), female gender (OR: 7.69,
      95% CI 3.23-20.0, P < 0.001), systolic blood pressure >=140 mmHg (OR: 2.85, 95%
      CI 1.27-6.41, P = 0.011), and duration of hypertension (OR: 3.59, 95% CI 1.47
      8.76, P = 0.005) were independent predictors of left ventricular hypertrophy.
      Angiotensin converting enzyme (ACE) inhibitors were the only antihypertensive
      drugs associated with lower risk of left ventricular hypertrophy (OR: 0.08, 95%
      CI 0.03-0.19, p < 0.001). CONCLUSIONS: Left ventricular hypertrophy was found to
      be highly prevalent in hypertensive patients in Ethiopia. ACE inhibitors were the
      only antihypertensive drugs associated with reduced risk of LVH. We thus
      recommend strategies to early detect and treat hypertension and to timely screen
      for LVH among patients with hypertension. Multicenter prospective studies in
      Africa settings would be ideal to identify the best antihypertensive agents in
      black Africans.

PMID- 24444397
TI  - Rituximab in recurrent idiopathic giant cell myocarditis after heart
      transplantation: a potential therapeutic approach.
AB  - Giant cell myocarditis (GCM) is a very aggressive form of myocardial
      inflammation. While immunosuppressive therapy is usually able to keep under
      control the disease and prolong the average transplant-free survival in many
      patients, effective therapeutic strategies to prevent or treat the recurrence of
      GCM in transplanted organs are still to be defined. We report the case of a young
      woman with idiopathic GCM who, despite immediate aggressive immunosuppressive
      therapy, rapidly progressed to irreversible heart failure and required urgent
      heart transplantation. Yet, 2 months later, the disease recurred in the
      transplanted heart, despite an intensive four-drug antirejection regimen. The
      introduction of rituximab, an anti-CD20 monoclonal antibody, 375 mg/m(2) /week
      i.v. for four consecutive weeks and then every 4 months as maintenance therapy,
      determined a complete and steady clinical remission of the disease. After
      nineteen months since rituximab administration, the patient is doing well and
      repeated follow-up endo-myocardial biopsies confirmed the complete resolution of
      myocardial inflammation. Our experience seems to suggest that rituximab can be a
      reasonably effective and safe therapeutic option in GCM recurring in transplanted
      organs.

PMID- 24444398
TI  - Systematic review and meta-analysis of the effect of various laser wavelengths in
      the treatment of peri-implantitis.
AB  - BACKGROUND: The primary aim of this systematic review is to address the following
      focused question: Is laser therapy, as a monotherapy or as an adjunctive therapy,
      an efficacious treatment modality for patients with peri-implantitis? METHODS:
      The PubMed database of the U.S. National Library of Medicine and the Cochrane
      Central Register of Controlled Trials were electronically searched, complemented
      by manual searches up to June 2013. RESULTS: The search yielded 137 titles and
      abstracts. After initial screening, 15 of 137 publications were scrutinized
      during the second phase of the review. In the second phase, nine articles were
      excluded from the analysis and six controlled, clinical studies were selected.
      Narrative synthesis of the results revealed that non-surgical laser treatment
      with a single application of either an erbium:yttrium-aluminum-garnet (Er:YAG)
      (2,940-nm) laser or a diode (660-nm) laser in combination with a phenothiazine
      chloride dye is efficient in controlling inflammation around treated implants for
      at least 6 months following intervention, whereas it has only a mild effect on
      reduction in probing depth (PD) and gain in clinical attachment level (CAL).
      There is limited information regarding the clinical application of the CO2 (10.6
      um) laser in the surgical treatment of peri-implantitis; however, its use may be
      promising. A meta-analysis could be performed only for the efficacy of Er:YAG
      laser due to the heterogeneity of the studies and the limited amount of data
      available. Meta-analysis did not reveal statistically significant evidence for
      treatment effects in reducing PD and CAL levels in comparison to controls.
      CONCLUSIONS: Based on the limited information currently available, any
      superiority of laser treatment in comparison to conventional treatment of peri
      implantitis could not be identified. Considering the high heterogeneity and the
      low number of included studies, the authors cautiously conclude that non-surgical
      laser therapy may be investigated as phase I therapy for the treatment of peri
      implantitis. Future research should emphasize detailed description of the
      specific laser characteristics and power settings in clinical studies.

PMID- 24444399
TI  - Influence of crown/implant ratio on marginal bone loss: a systematic review.
AB  - BACKGROUND: With the increased use of short dental implants (<10 mm), a high
      crown/implant (C/I) ratio has become a common finding. However, the effect of the
      C/I ratio on the marginal bone loss (MBL) has not yet been examined extensively.
      Hence, the aim of the present systematic review is to explore the influence of
      the C/I ratio on the success rate and MBL of dental implants. METHODS: Three
      electronic databases (PubMed, Ovid MEDLINE, and Cochrane Central) and a manual
      search for human trials with a minimal follow-up of 6 months are used for the
      present study. A statistical analysis of the influence of the C/I ratio was
      performed on the peri-implant MBL while considering follow-up period, type of
      implants, implant connection, and technical and biologic complications. RESULTS:
      One hundred ninety-six potential articles were identified on the selected
      databases. Only 57 articles were selected for full-text evaluation. According to
      the inclusion criteria, a total of 13 articles were included in this systematic
      review. A significant negative association between the C/I ratio and the MBL was
      found (P = 0.012). However, no statistically significant difference was found (P
      >0.15) for potential effects regarding the observation period, the type of
      implant connection, or between both methods of evaluating the C/I ratio.
      CONCLUSIONS: Within the limitations of the present study, the C/I ratio of
      implant-supported restorations has an effect on peri-implant marginal bone level.
      Within the range of 0.6/1 to 2.36/1, the higher the C/I ratio, the less the peri
      implant MBL.

PMID- 24444400
TI  - Attachment of Porphyromonas gingivalis to corroded commercially pure titanium and
      titanium-aluminum-vanadium alloy.
AB  - BACKGROUND: Titanium dental material can become corroded because of
      electrochemical interaction in the oral environment. The corrosion process may
      result in surface modification. It was hypothesized that a titanium surface
      modified by corrosion may enhance the attachment of periodontal pathogens. This
      study evaluates the effects of corroded titanium surfaces on the attachment of
      Porphyromonas gingivalis. METHODS: Commercially pure titanium (cp-Ti) and
      titanium-aluminum-vanadium alloy (Ti-6Al-4V) disks were used. Disks were
      anodically polarized in a standard three-electrode setting in a simulated oral
      environment with artificial saliva at pH levels of 3.0, 6.5, or 9.0. Non-corroded
      disks were used as controls. Surface roughness was measured before and after
      corrosion. Disks were inoculated with P. gingivalis and incubated anaerobically
      at 37 degrees C. After 6 hours, the disks with attached P. gingivalis were
      stained with crystal violet, and attachment was expressed based on dye absorption
      at optical density of 550 nm. All assays were performed independently three times
      in triplicate. Data were analyzed by two-way analysis of variance, the Tukey
      honestly significant difference test, t test, and Pearson's correlation test
      (alpha = 0.05). RESULTS: Both cp-Ti and Ti-6Al-4V alloy-corroded disks promoted
      significantly more bacterial attachment (11.02% and 41.78%, respectively; P
      <0.0001) than did the non-corroded controls. Significantly more (11.8%) P.
      gingivalis attached to the cp-Ti disks than to the Ti-6Al-4V alloy disks (P
      <0.05). No significant difference in P. gingivalis attachment was noted among the
      corroded groups for both cp-Ti and Ti-6Al-4V alloy (P >0.05). There was no
      significant correlation between surface roughness and P. gingivalis attachment.
      CONCLUSION: A higher degree of corrosion on the titanium surface may promote
      increased bacterial attachment by oral pathogens.

PMID- 24444401
TI  - Personalizing the management of heart failure in congenital heart disease:
      challenges and opportunities.

PMID- 24444403
TI  - Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non
      small-cell lung cancer.

PMID- 24444404
TI  - Genome-wide association and pharmacological profiling of 29 anticancer agents
      using lymphoblastoid cell lines.
AB  - AIM: Association mapping with lymphoblastoid cell lines (LCLs) is a promising
      approach in pharmacogenomics research, and in the current study we utilized LCLs
      to perform association mapping for 29 chemotherapy drugs. MATERIALS & METHODS:
      Currently, we use LCLs to perform genome-wide association mapping of the
      cytotoxic response of 520 European-Americans to 29 different anticancer drugs;
      the largest LCL study to date. A novel association approach using a multivariate
      analysis of covariance design was employed with the software program MAGWAS,
      testing for differences in the dose-response profiles between genotypes without
      making assumptions about the response curve or the biologic mode of association.
      Additionally, by classifying 25 of the 29 drugs into eight families according to
      structural and mechanistic relationships, MAGWAS was used to test for
      associations that were shared across each drug family. Finally, a unique
      algorithm using multivariate responses and multiple linear regressions across
      pairs of response curves was used for unsupervised clustering of drugs. RESULTS:
      Among the single-drug studies, suggestive associations were obtained for 18 loci,
      12 within/near genes. Three of these, MED12L, CHN2 and MGMT, have been previously
      implicated in cancer pharmacogenomics. The drug family associations resulted in
      four additional suggestive loci (three contained within/near genes). One of these
      genes, HDAC4, associated with the DNA alkylating agents, shows possible clinical
      interactions with temozolomide. For the drug clustering analysis, 18 of 25 drugs
      clustered into the appropriate family. CONCLUSION: This study demonstrates the
      utility of LCLs in identifying genes that have clinical importance in drug
      response and for assigning unclassified agents to specific drug families, and
      proposes new candidate genes for follow-up in a large number of chemotherapy
      drugs.

PMID- 24444405
TI  - Association between migraine and ACE gene (insertion/deletion) polymorphism: the
      BioBIM study.
AB  - AIM: In the present case-control study, we investigated the correlation between
      the common ACE insertion/deletion (I/D) polymorphism and migraine. MATERIALS &
      METHODS: Genotyping of the ACE I/D variant was performed in 502 Caucasian
      patients with migraine and 323 age-, sex- and race/ethnicity-matched healthy
      controls. We investigated associations between ACE genetic variants and
      sociodemographic and/or clinical features of migraineurs. RESULTS: We found a
      significant association between ACE insertion/insertion (I/I) polymorphism and
      lower use of pharmacological prophylaxis in migraine patients with aura and in
      those with chronic migraine. Moreover, ACE I/I polymorphism was significantly
      more common in migraine patients with aura who had a negative family history of
      migraine. CONCLUSION: Our data suggest that although the ACE I/D polymorphism is
      not a direct risk factor for migraine, the ACE I/I genotype may influence the
      clinical feature of this disease being associated with reduced use of
      prophylactic agents in patients with migraine with aura and in those with chronic
      migraine.

PMID- 24444406
TI  - Human pharmacogenomic variation of antihypertensive drugs: from population
      genetics to personalized medicine.
AB  - AIM: To investigate the human pharmacogenetic variation related to
      antihypertensive drugs, providing a survey of functional interpopulation
      differences in hypertension pharmacogenes. MATERIALS & METHODS: The study was
      divided into two stages. In the first stage, we analyzed 1249 variants located in
      57 hypertension pharmacogenes. This first-stage analysis confirmed that
      geographic origin strongly affects hypertension pharmacogenomic variation and
      that 31 pharmacogenes are geographically differentiated. In the second stage, we
      focused our attention on the ethnic-differentiated pharmacogenes, investigating
      55,521 genetic variants. In silico analyses were performed to predict the effect
      of genetic variation. RESULTS: Our analyses indicated functional interpopulation
      differences, suggesting insight into the mechanisms of antihypertensive drug
      response. Moreover, our data suggested that rare variants mainly determine the
      functionality of genes related to antihypertensive drugs. CONCLUSION: Our study
      provided important knowledge about the genetics of the antihypertensive drug
      response, suggesting that next-generation sequencing technologies may develop
      reliable pharmacogenetic tests for antihypertensive drugs.

PMID- 24444407
TI  - Different phenotypes of the NAT2 gene influences hydralazine antihypertensive
      response in patients with resistant hypertension.
AB  - AIM: Hydralazine, a vasodilator used in resistant hypertension (RH) treatment is
      metabolized by an acetylation reaction mediated by N-acetyltransferase 2, the
      activity of which depends on NAT2 polymorphisms. Our aim was to evaluate whether
      different acetylation phenotypes influenced the antihypertensive effect of
      hydralazine in patients with RH. PATIENTS & METHODS: DNA samples from 169 RH
      patients using hydralazine were genotyped by sequencing the NAT2 coding region,
      and acetylation phenotypes were defined. RESULTS: Sixty-five patients (38.5%)
      were intermediate, 60 (35.5%) slow and 21 (12.4%) fast acetylators. Twenty-three
      (13.6%) patients were indeterminate. Upon association analysis, only slow
      acetylators had significant blood pressure reductions after hydralazine use, with
      mean 24-h systolic and diastolic blood pressure reductions of 9.2 and 5.5 mmHg.
      Four patients presented hydralazine adverse effects resulting in drug withdrawal,
      three of them were slow acetylators. CONCLUSION: The slow acetylation phenotype,
      determined by polymorphisms within NAT2, influenced both the antihypertensive and
      adverse effects of hydralazine in RH.

PMID- 24444408
TI  - CYP3A5 and CYP3A4, but not ABCB1 polymorphisms affect tacrolimus dose-adjusted
      trough concentrations in kidney transplant recipients.
AB  - BACKGROUND: Tacrolimus (TAC), acting as a calcineurin inhibitor, is an
      immunosuppressant widely used after kidney transplantation. TAC requires blood
      concentration monitoring due to large interindividual variability in its
      pharmacokinetics and a narrow therapeutic index. Since genetic factors are
      considered responsible for a part of the observed pharmacokinetic variability,
      hereby SNPs within the CYP3A4, CYP3A5 and ABCB1 genes in kidney transplant
      patients of Polish Caucasian origin were investigated. PATIENTS & METHODS: A
      total of 241 patients treated with TAC through the first year after kidney
      transplantation were genotyped for the presence of common SNPs: rs776746:A>G
      (CYP3A5*3), rs35599367:C>T (CYP3A4*22), rs2740574:A>G (CYP3A4*1B) and
      rs1045642:C>T (ABCB1 3435C>T) using TaqMan((r)) assays. RESULTS: CYP3A5
      expressers received significantly higher weight-adjusted TAC doses, and were
      characterized by markedly lower C0 and dose adjusted C0 values in the course of
      treatment. CYP3A4*1B was significantly associated with TAC pharmacokinetics in
      univariate analysis. Impact of the CYP3A4*22 allele was significant only at
      particular time points, that is, 3 months after transplantation, with marginal
      significance 6 months after transplantation. The ABCB1 genotype did not influence
      TAC pharmacokinetics. Multivariate analysis of all the studied loci demonstrated
      that only the CYP3A5*1 (starting from month 1) and CYP3A4*22 alleles (at 3 and 6
      months) were independent predictors of TAC dose-adjusted C0. CONCLUSION: Our
      results confirm the impact of the CYP3A4*22 allele on TAC pharmacokinetics, as a
      second significant genetic factor (in addition to the CYP3A5*1 allele)
      influencing TAC dose-adjusted blood concentrations in kidney transplant
      recipients.

PMID- 24444409
TI  - Patterns of variation influencing antipsychotic treatment outcomes in South
      African first-episode schizophrenia patients.
AB  - AIM: Many antipsychotic pharmacogenetics studies have been performed examining
      candidate genes or known variation; however, our understanding of the genetic
      factors involved in antipsychotic pharmacogenetic traits remains limited.
      MATERIALS & METHODS: A well-characterized cohort of first-episode schizophrenia
      (FES) patients was used to identify a subset of nonresponders and responders to
      antipsychotic treatment for exome sequencing (n = 11). The variation observed in
      the responders and nonresponders was subsequently compared and a prioritization
      strategy was employed to identify variants for genotyping in the entire FES
      cohort (n = 103) as well as an additional Xhosa schizophrenia cohort (n = 222).
      RESULTS: Examination of coding variation revealed a potential role for rare loss
      of-function variants in treatment response outcomes. One variant, rs11368509, was
      found to be weakly associated with better treatment outcomes in the FES cohort (p
      = 0.057) and the Xhosa schizophrenia cohort (p = 0.016). In addition, the
      majority of the loss-of-function variation that was considered likely to be
      involved in antipsychotic treatment response was either novel or rare in Asian
      and European populations. CONCLUSION: This pilot study has highlighted the
      importance of exome sequencing for antipsychotic pharmacogenomics studies,
      particularly in African individuals. Furthermore, the results emphasize once
      again the complexity of antipsychotic pharmacogenomics and the need for future
      research.

PMID- 24444410
TI  - Pharmacogenomic implications of population admixture: Brazil as a model case.
AB  - The heterogeneous Brazilian population, with European, African and Amerindian
      ancestral roots is a model case for exploring the impact of population admixture
      on the frequency distribution of polymorphisms in pharmacogenes, and the design
      and interpretation of pharmacogenomics trials. Examples drawn from studies
      carried out by researchers of the Brazilian pharmacogenomics network, support the
      following conclusions: the distribution of polymorphisms varies across
      geographical regions and self-reported 'race/color' categories, and is best
      modeled as continuous functions of individual proportions of European and African
      ancestry; the differential frequency of polymorphisms impacts the calculations of
      sample sizes required for adequate statistical power in clinical trials performed
      in different segments of the Brazilian population; and extrapolation of
      pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued
      with uncertainty. Data for warfarin and tacrolimus are reviewed to highlight the
      advantages and challenges of performing pharmacogenomic trials in Brazilians. 

PMID- 24444412
TI  - Pancreatic gene variants potentially associated with dipeptidyl peptidase-4
      inhibitor treatment response in Type 2 diabetes.
AB  - In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11,
      ABCC8, MTNR1B and WFS1 are mainly restricted to beta cells to maintain glucose
      homeostasis. We have identified these genes as the main regulators of incretin
      mediated actions, and therefore they may potentially influence the response of
      DPP-4 inhibitors. This review represents the first detailed exploration of
      pancreatic beta-cell genes and their variant mechanisms, which could potentially
      affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on
      the signaling pathways of these genes to understand their roles in
      gastrointestinal incretin-mediated effects; and finally, we sought to associate
      gene mechanisms with their Type 2 diabetes risk variants to predict the responses
      of DPP-4 inhibitors for this disease. 

PMID- 24444411
TI  - Pharmacogenetics of nicotine addiction: role of dopamine.
AB  - The neurotransmitter dopamine (DA) plays a central role in addictive disorders,
      including nicotine addiction. Specific DA-related gene variants have been studied
      to identify responsiveness to treatment for nicotine addiction. Genetic variants
      in DRD2, DRD4, ANKK1, DAT1, COMT and DBH genes show some promise in informing
      personalized prescribing of smoking cessation pharmacotherapies. However, many
      trials studying these variants had small samples, used retrospective design or
      were composed of mainly self-identified Caucasian individuals. Furthermore, many
      of these studies lacked a comprehensive measurement of nicotine metabolism rate,
      did not assess the roles of sex or the menstrual cycle, and did not investigate
      the role of rare variants and/or epigenetic factors. Future work should be
      conducted addressing these limitations to more effectively utilize DA genetic
      information to unlock the potential of smoking cessation pharmacogenetics. 

PMID- 24444413
TI  - Conserved genetic regions across angiosperms as tools to develop single-copy
      nuclear markers in gymnosperms: an example using cycads.
AB  - Several individuals of the Caribbean Zamia clade and other cycad genera were used
      to identify single-copy nuclear genes for phylogeographic and phylogenetic
      studies in Cycadales. Two strategies were employed to select target loci: (i) a
      tblastX search of Arabidopsis conserved ortholog sequence (COS) set and (ii) a
      tblastX search of Arabidopsis-Populus-Vitis-Oryza Shared Single-Copy genes (APVO
      SSC) against the EST Zamia databases in GenBank. From the first strategy, 30 loci
      were selected, and from the second, 16 loci. In both cases, the matching GenBank
      accessions of Zamia were used as a query for retrieving highly similar sequences
      from Cycas, Picea, Pinus species or Ginkgo biloba. After retrieving and aligning
      all the sequences in each locus, intron predictions were completed to assist in
      primer design. PCR was carried out in three rounds to detect paralogous loci. A
      total of 29 loci were successfully amplified as a single band of which 20 were
      likely single-copy loci. These loci showed different diversity and divergence
      levels. A preliminary screening allowed us to select 8 promising loci (40S, ATG2,
      BG, GroES, GTP, LiSH, PEX4 and TR) for the Zamia pumila complex and 4 loci
      (COS26, GroES, GTP and HTS) for all other cycad genera. 

PMID- 24444414
TI  - A randomized prospective study comparing the efficacy of on-demand therapy versus
      continuous therapy for 6 months for long-term maintenance with omeprazole 20 mg
      in patients with gastroesophageal reflux disease in Japan.
AB  - AIM: To assess the efficacy of continuous therapy (cont) and on-demand therapy
      (on-demand) as maintenance therapy for gastroesophageal reflux disease (GERD).
      METHODS: Patients with upper GI endoscopy (EGD)-proven GERD who completed 8 weeks
      of initial therapy were randomized to cont (omeprazole 20 mg od) or on-demand
      (omeprazole 20 mg on-demand) group. Assessments by the Global Overall Symptom
      (GOS) scale at baseline (at the start of maintenance therapy) and at 8-week, 16
      week, and 24-week visits were made and EGD was performed at 24 weeks. Symptom
      relief was defined as percentages of patients whose GOS score of 1 or 2. RESULTS:
      Of the 117 enrolled patients, cont/on-demand was 59/58 and nonerosive reflux
      disease (NERD)/reflux esophagitis (RE) before the initial therapy was 35/82.
      Symptom relief in cont/on-demand were 57.6%/48.3% at baseline (n.s.), 66.7%/54.7%
      at 8 week (n.s.), 64.6%/54.7% at 16 weeks (n.s.), and 66.7%/74.0% at 24 weeks
      (n.s.). When subjects were divided into NERD and RE, symptom relief in cont/on
      demand were 33.3%/41.2% at baseline (n.s.), 43.8%/64.3% at 8 weeks (n.s.),
      50.0%/42.9% at 16 weeks (n.s.), and 50.0%/69.2% at 24 weeks (n.s.) in NERD, while
      those were 68.3%/51.2% at baseline (n.s.), 76.3%/51.3% at 8 weeks (p < 0.05),
      70.6%/59.0% at 16 weeks (n.s.), and 72.7%/75.7% at 24 weeks (n.s.) in RE,
      respectively. At 24-week EGD, all patients in NERD remained as NERD but number of
      healed patients was significantly higher in cont (85.3%) than in on-demand
      (44.4%) (p < 0.01) in RE. CONCLUSIONS: Since NERD is defined by symptoms, as a
      result of the limited efficacy of continuous therapy, on-demand therapy would be
      sufficient as maintenance therapy in NERD patients. Regarding RE, continuous
      therapy would be recommended in terms of reduced symptoms and maintaining mucosal
      healing.

PMID- 24444416
TI  - Effects of methoxy and formyl substituents on the energetics and reactivity of
      alpha-naphthalenes: a calorimetric and computational study.
AB  - A combined experimental and computational study was developed to evaluate and
      understand the energetics and reactivity of formyl and methoxy alpha-naphthalene
      derivatives. Static bomb combustion calorimetry and the Calvet microcalorimetry
      were the experimental techniques used to determine the standard (p(o)=0.1 MPa)
      molar enthalpies of formation, in the liquid phase, DeltafHm(o)(l), and of
      vaporization, Deltal(g)Hm(o), at T=298.15K, respectively, of the two liquid
      naphthalene derivatives. Those experimental values were used to derive the values
      of the experimental standard molar enthalpies of formation, in the gaseous phase,
      DeltafHm(o)(g), of 1-methoxynaphthalene, (-3.0 +/- 3.1)kJmol(-1), and of 1
      formylnaphthalene, (36.3 +/- 4.1)kJ mol(-1). High-level quantum chemical
      calculations at the composite G3(MP2)//B3LYP level were performed to estimate the
      values of the DeltafHm(o)(g) of the two compounds studied resulting in values in
      very good agreement with experimental ones. Natural bond orbital (NBO)
      calculations were also performed to determine more about the structure and
      reactivity of this class of compounds.

PMID- 24444415
TI  - LinA2, a HCH-converting bacterial enzyme that dehydrohalogenates HBCDs.
AB  - Hexabromocyclododecanes (HBCDs) and hexachlorocyclohexanes (HCHs) are lipophilic,
      polyhalogenated hydrocarbons with comparable stereochemistry. Bacterial evolution
      in HCH-contaminated soils resulted in the development of several Spingomonadaceae
      which express a series of HCH-converting enzymes. We showed that LinB, a
      haloalkane dehalogenase from Sphingobium indicum B90A, also transforms various
      HBCDs besides HCHs. Here we present evidence that LinA2, another dehalogenase
      from S. indicum also converts certain HBCDs to pentabromocyclododecenes (PBCDEs).
      Racemic mixtures of alpha-, beta-, gamma-HBCDs, a mixture of them, and delta
      HBCD, a meso form, were exposed to LinA2. Substantial conversion of (-)beta-HBCD
      was observed, but all other stereoisomers were not transformed significantly. The
      enantiomeric excess (EE) of beta-HBCDs increased up to 60% in 32 h, whereas EE
      values of alpha- and gamma-HBCDs were not affected. Substrate conversion and
      product formation were described with second-order kinetic models. One major
      (P1beta) and possibly two minor (P2beta, P3beta) metabolites were detected.
      Respective mass spectra showed the characteristic isotope pattern of PBCDEs, the
      HBr elimination products of HBCDs. Michaelis-Menten parameters KM=0.47 +/- 0.07
      MUM and vmax=0.17 +/- 0.01 MUmoll(-1)h(-1) were deduced from exposure data with
      varying enzyme/substrate ratios. LinA2 is more substrate specific than LinB, the
      latter converted all tested HBCDs, LinA2 only one. The widespread HCH pollution
      favored the selection and evolution of bacteria converting these compounds. We
      found that LinA2 and LinB, two of these HCH-converting enzymes expressed in S.
      indicum B90A, also dehalogenate HBCDs to lower brominated compounds, indicating
      that structural similarities of both classes of compounds are recognized at the
      level of substrate-protein interactions.

PMID- 24444417
TI  - Emissions of decamethylcyclopentasiloxane from Chicago.
AB  - Decamethylcyclopentasiloxane (D5) is a high-production-volume chemical that is
      emitted to air in tens of thousands of tonnes each year globally. However,
      specific information about emission rates to air is still limited. Here we
      present an estimate of D5 emissions from the city of Chicago based on
      measurements that have recently been published. We used a multimedia
      environmental fate model parameterized for Chicago to back-calculate the emission
      rate of D5 from the measurements. Our estimated average emission rate for D5 is
      500 (2.5-to-97.5-percentile interval: 260-1100) kg d(-1). The corresponding per
      capita emissions of 190 (100-420) mg capita(-1)d(-1) agree well with previous
      estimates for Europe and North America.

PMID- 24444418
TI  - Untargeted metabolomics as a screening tool for estimating compliance to a
      dietary pattern.
AB  - There is a growing interest in studying the nutritional effects of complex diets.
      For such studies, measurement of dietary compliance is a challenge because the
      currently available compliance markers cover only limited aspects of a diet. In
      the present study, an untargeted metabolomics approach was used to develop a
      compliance measure in urine to distinguish between two dietary patterns. A
      parallel intervention study was carried out in which 181 participants were
      randomized to follow either a New Nordic Diet (NND) or an Average Danish Diet
      (ADD) for 6 months. Dietary intakes were closely monitored over the whole study
      period, and 24 h urine samples as well as weighed dietary records were collected
      several times during the study. The urine samples were analyzed by UPLC-qTOF-MS,
      and a partial least-squares discriminant analysis with feature selection was
      applied to develop a compliance model based on data from 214 urine samples. The
      optimized model included 52 metabolites and had a misclassification rate of 19%
      in a validation set containing 139 samples. The metabolites identified in the
      model were markers of individual foods such as citrus, cocoa-containing products,
      and fish as well as more general dietary traits such as high fruit and vegetable
      intake or high intake of heat-treated foods. It was easier to classify the ADD
      diet than the NND diet probably due to seasonal variation in the food composition
      of NND and indications of lower compliance among the NND subjects. In conclusion,
      untargeted metabolomics is a promising approach to develop compliance measures
      that cover the most important discriminant metabolites of complex diets. 

PMID- 24444419
TI  - Tnfaip8 l1/Oxi-beta binds to FBXW5, increasing autophagy through activation of
      TSC2 in a Parkinson's disease model.
AB  - Abnormal autophagy may contribute to neurodegeneration in Parkinson's disease
      (PD). However, it is largely unknown how autophagy is dysregulated by oxidative
      stress (OS), one of major pathogenic causes of PD. We recently discovered the
      potential autophagy regulator gene family including Tnfaip8/Oxi-alpha, which is a
      mammalian target of rapamycin (mTOR) activator down-regulated by OS in
      dopaminergic neurons (J. Neurochem., 112, 2010, 366). Here, we demonstrate that
      the OS-induced Tnfaip8 l1/Oxi-beta could increase autophagy by a unique mechanism
      that increases the stability of tuberous sclerosis complex 2 (TSC2), a critical
      negative regulator of mTOR. Tnfaip8 l1/Oxi-beta and Tnfaip8/Oxi-alpha are the
      novel regulators of mTOR acting in opposition in dopaminergic (DA) neurons.
      Specifically, 6-hydroxydopamine (6-OHDA) treatment up-regulated Tnfaip8 l1/Oxi
      beta in DA neurons, thus inducing autophagy, while knockdown of Tnfaip8 l1/Oxi
      beta prevented significantly activation of autophagic markers by 6-OHDA. FBXW5
      was identified as a novel binding protein for Tnfaip8 l1/Oxi-beta. FBXW5 is a
      TSC2 binding receptor within CUL4 E3 ligase complex, and it promotes proteasomal
      degradation of TSC2. Thus, Tnfaip8 l1/Oxi-beta competes with TSC2 to bind FBXW5,
      increasing TSC2 stability by preventing its ubiquitination. Our data show that
      the OS-induced Tnfaip8 l1/Oxi-beta stabilizes TSC2 protein, decreases mTOR
      phosphorylation, and enhances autophagy. Therefore, altered regulation of Tnfaip8
      l1/Oxi-beta may contribute significantly to dysregulated autophagy observed in
      dopaminergic neurons under pathogenic OS condition. Dysfunctional autophagy is
      frequently observed in post-mortem brains of patients and animal models of
      Parkinson's disease. In dopaminergic neurons of the 6-hydroxydopamine (6-OHDA)
      model, oxidative stress induces Tnfaip8 l1/Oxi-beta, which results in increased
      autophagy by its exclusive binding with FBXW5 to stabilize TSC2. Thus, altered
      regulation of Tnfaip8 l1/Oxi-beta may contribute to dysregulated autophagy in
      dopaminergic neurons under pathogenic oxidative stress, implicating both Oxi-beta
      and FBXW5 as potential intervention targets for dysfunctional autophagy in
      dopaminergic neurons under oxidative stress. 

PMID- 24444420
TI  - The medial cortical pedicle screw--a new technique for cervical pedicle screw
      placement with partial drilling of medial cortex.
AB  - BACKGROUND CONTEXT: Studies on cadavers have shown that the appropriate insertion
      of cervical pedicle screw (C3-C7) should be done from a more lateral point and at
      a steeper angle in the axial plane, than that described by Abumi et al., to
      decrease the chances of lateral perforation. PURPOSE: We describe a new technique
      for cervical pedicle screw (CPS) placement (C3-C7) using high-speed pneumatic
      drill with partial drilling of medial cortex for decreasing the chances of
      lateral perforation. STUDY DESIGN: Description of new surgical technique with
      retrospective data analysis. PATIENT SAMPLE: Twenty-five patients undergoing
      cervical spine surgery with CPS instrumentation in the lower cervical spine (C3
      C7) from April 2011 to October 2012 at our institute were included in the study.
      OUTCOME MEASURES: All patients were evaluated with computed tomography scans
      postoperatively for the assessment of pedicle screw placement. Pedicle screw
      perforations were graded with the following criteria: Grade I perforations having
      <=50% of the screw outside the pedicle and Grade II perforations having >50% of
      the screw outside the pedicle. Clinical complications directly related to CPS
      placement were also recorded. METHODS: Twenty-five patients undergoing surgery
      with CPS instrumentation (C3-C7) at our institute between April 2011 and October
      2012 were included in the study. Thirteen patients had cervical trauma, 10 had
      cervical spondylotic myelopathy, 1 had congenital cervico-dorsal scoliosis, and 1
      was a patient with ankylosing spondylitis. Pedicle screw insertion was made
      according to the technique by Abumi et al., with the use of blunt pedicle probes
      in eight of these cases (Group I). In the other 17 cases (Group II), the pilot
      hole was made with the use of 2-mm diamond tipped burr, partially drilling the
      medial cortex and entering the vertebral body with the burr itself. RESULTS: A
      total of 131 CPSs (C3-C7) were inserted in 25 patients. In Group I, 43 pedicle
      screws were placed and 88 screws were placed in Group II, with partial drilling
      of medial cortex. Lateral perforations: in Group-I, more of lateral perforations
      were observed with 18.6% Grade I and 9.3% Grade II lateral perforations. In Group
      II, the lateral perforations were lower with 7.95% Grade I and 1.1% of Grade II
      lateral perforations. I Group-I, medial perforations were lower with 11.62% Grade
      I and 2.3% Grade II perforations. In Group II, the Grade I and Grade II medial
      perforations were 30.7% and 4.5%, respectively. The lateral perforations were
      more at C3, C4 levels, and the medial perforation was maximum at C5 level. No
      clinical neurovascular complications, directly related to screw placements, were
      seen in either of the groups postoperatively. CONCLUSIONS: With the use of the
      technique by Abumi et al., more than half of the cervical pedicle screw
      perforations described are lateral. Use of a blunt pedicle probe usually directs
      the surgeon toward the lateral cortex as the medial cortex is thicker and
      stronger. With the new medial cortical pedicle screw technique described, lateral
      perforations were low. However, surgeons attempting this technique should be
      aware of the increase in medial perforations experienced by the authors with the
      new technique. The study gives an additional option of technique to be considered
      by surgeons already using CPS placements in selected patients. Further evaluation
      for reproducibility of the medial cortical pedicle screw technique by other
      surgeons and testing of biomechanical strength of the screws is required.

PMID- 24444421
TI  - Spinal cord herniation or intradural arachnoid cyst?

PMID- 24444422
TI  - [Follicular non-Hodgkin lymphoma-associated dermatomyositis].

PMID- 24444423
TI  - Spontaneous reactivation of hepatitis B virus replication in an HIV coinfected
      patient with isolated anti-Hepatitis B core antibodies.
AB  - Co-infections with HBV (hepatitis B virus) occur in HIV (human immunodeficiency
      virus) patients frequently. It has been reported that an effective treatment of
      HIV can also lead to a suppression of HBV and to anti-HBs seroconversion in HBV
      infected patients. Here, we report a spontaneous reactivation of HBV replication
      in an HIV-infected patient with anti-HBc as the only marker of chronic HBV
      infection. The patient was known to be coinfected with HIV and HBV for years and
      the HBV DNA was measured repeatedly at low levels. A significant increase of HBV
      DNA up to 1.7 x 107 IU/ml was found accompanied with clinical symptoms of
      hepatitis. Multiple mutations occurred in the S gene during the flare-up of HBV
      as shown by sequencing, including I103T, K122R, M133I, F134V, D144E, V164E and
      L175S. Anti-HIV/HBV treatment led to a resolution of symptoms and to a decrease
      in the HIV RNA and HBV DNA viral load. It is possible that the accumulated
      mutations during HBV replication were selected and responsible for the
      reactivation.

PMID- 24444424
TI  - Sustained multiplicity in everyday cholesterol reduction: repertoires and
      practices in talk about 'healthy living'.
AB  - This article is concerned with talk about and the practices of healthy living in
      relation to cholesterol reduction. It draws on qualitative interviews with 89
      people who are current or former users of either cholesterol-lowering functional
      foods or statins for cardiovascular risk reduction. Focusing on data about
      everyday activities including food preparation, shopping and exercise, we
      illustrate four repertoires that feature in talk about cholesterol reduction
      (health, pleasure, sociality and pragmatism). Using Gilbert and Mulkay's notion
      of a 'reconciliation device', we suggest ways in which apparently contradictory
      repertoires are combined (for example, through talk about moderation) or kept
      apart. We suggest that, in contrast to the interactiveness of the repertoires of
      health and pleasure, a pragmatic repertoire concerning food provisioning, storage
      and cooking as well as the realities of exercise, appears distinct from talk
      about health and is relatively inert. Finally we consider the implications of
      these discursive patterns for daily practices. Our data suggest there is little
      emphasis on coherence in people's practices and illustrate the significance of
      temporal, spatial and social distribution in allowing people to pursue different
      priorities in their everyday lives. Rather than the calculated trade-offs of
      earlier medical sociology we draw on Mol to foreground the possibility of
      sustained multiplicity in daily practices. 

PMID- 24444425
TI  - Uterine junctional zone at three-dimensional transvaginal ultrasonography in
      patients with recurrent miscarriage: a new diagnostic tool?
AB  - OBJECTIVE: To evaluate the characteristics of the uterine junctional zone (JZ) by
      three-dimensional (3D) transvaginal sonography (TVS) in women with recurrent
      miscarriage (RM) as compared to normal fertile controls. STUDY DESIGN: The
      thickness and the morphology of the JZ were evaluated in 75 women with a history
      of RM due to different causes and in 20 fertile women without a history of
      miscarriages or pelvic disease. All patients included in the study were selected
      among those who attended the outpatient clinic of "Tor Vergata" University. The
      JZ characteristics were evaluated in the midluteal phase of the cycle on the
      uterine coronal section obtained by 3D TVS. RESULTS: Patients with RM showed a JZ
      maximum thickness significantly increased when compared to that observed in
      control group (5.8+/-0.7 vs. 5.0+/-1.1mm). When grouped according to the
      different causes of RM, all groups of patients with RM showed an increased JZ
      thickness when compared to fertile women, with the exception of those with anti
      phospholipid antibody syndrome, probably due to the small number of cases with
      this pathology. CONCLUSIONS: A thickened JZ could be an independent indicator of
      the risk of miscarriage and may represent an important contributing factor to
      some causes of RM. These observations may offer new perspectives for the
      screening and treatment of patients with RM. Although further studies are needed
      to ascertain if the reduction of the JZ thickness can determine a better
      pregnancy outcome, 3D TVS evaluation of the JZ could provide the opportunity to
      identify women in which appropriate therapeutic protocols can improve the
      possibility of successful pregnancy.

PMID- 24444426
TI  - In the absence of conflicting testimony young children trust inaccurate
      informants.
AB  - The present research investigated the nature of the inferences and decisions
      young children make about informants with a prior history of inaccuracies. Across
      three experiments, 3- and 4-year-olds (total N = 182) reacted to previously
      inaccurate informants who offered testimony in an object-labeling task. Of
      central interest was children's willingness to accept information provided by an
      inaccurate informant in different contexts of being alone, paired with an
      accurate informant, or paired with a novel (neutral) informant. Experiments 1 and
      2 showed that when a previously inaccurate informant was alone and provided
      testimony that was not in conflict with the testimony of another informant,
      children systematically accepted the testimony of that informant. Experiment 3
      showed that children accepted testimony from a neutral informant over an
      inaccurate informant when both provided information, but accepted testimony from
      an inaccurate informant rather than seeking information from an available neutral
      informant who did not automatically offer information. These results suggest that
      even though young children use prior history of accuracy to determine the
      relative reliability of informants, they are quite willing to trust the testimony
      of a single informant alone, regardless of whether that informant had previously
      been reliable.

PMID- 24444427
TI  - Association of cannabinoid type 1 receptor and fatty acid amide hydrolase genetic
      polymorphisms in Chinese patients with irritable bowel syndrome.
AB  - BACKGROUND AND AIM: The endocannabinoid system is involved in the pathophysiology
      of irritable bowel syndrome (IBS). Here, we investigated whether genetic variants
      of the cannabinoid type 1 receptor (CNR1) and fatty acid amide hydrolase (FAAH)
      are associated with the pathogenesis of IBS. METHODS: In total, 292 patients with
      IBS and 298 healthy controls were enrolled. Polymerase chain reaction (PCR) and
      DNA sequencing were applied to determine the genotyping of polymorphic triplet
      AAT repeats located at the 3'-end of the CNR1 gene. The single nucleotide
      polymorphism (SNP) C385A at the FAAH gene (rs324420) was determined by PCR using
      TaqMan SNP Genotyping Assay Sets. RESULTS: A total of eight alleles with AAT
      triplet repeats in the CNR1 gene were detected. The alleles were divided into two
      groups (<= 10 and > 10) and three genotypes (<= 10/<= 10, <= 10/> 10, and > 10/>
      10). The frequency of > 10 alleles was significantly higher in the IBS group
      (90.6%) when compared with the control group {81.7%, P < 0.001, odds ratio (OR)
      (95% confidence interval [CI]) = -0.128}. In addition, the genotypes > 10/> 10
      were significantly associated with IBS (P < 0.001, OR [95% CI] = -0.163). The
      frequency of the A allele and the distribution of the AA genotype in the FAAH
      gene in the IBS group were not significantly different from those in the control
      group (P > 0.05), even though the frequency of the AA genotype was lower in the
      IBS group (1.0%) than that in the control group (3.4%, P = 0.089, OR [95% CI] =
      3.345). CONCLUSIONS: The variation in the (AAT)n repeat of the CNR1 gene
      conferred an increased risk for developing IBS, while rs324420 (C385) in the FAAH
      gene was not associated with IBS pathogenesis.

PMID- 24444428
TI  - Clinical and biochemical effects of 810 nm diode laser as an adjunct to
      periodontal therapy: a randomized split-mouth clinical trial.
AB  - OBJECTIVE: The aim of this clinical trial was to determine the clinical and
      biochemical efficacy of an 810 nm diode laser as an adjunct to scaling and root
      planing (SRP). BACKGROUND DATA: Lasers can achieve excellent tissue ablation with
      strong bactericidal and detoxification effects. The use of lasers is one of the
      most promising new technical modalities for nonsurgical periodontal treatment.
      However, the most effective wavelength and parameters for their use are still
      under investigation. METHODS: This study was designed as a single-blinded,
      randomized-controlled, split-mouth clinical trial. Twenty-one patients (12
      females and 9 males between 26 and 55 years of age), diagnosed with generalized
      chronic periodontitis, were included in the study. After initial periodontal
      therapy, which consisted of oral hygiene instructions and scaling, patients
      underwent two different treatment modalities. Test and control sites were chosen
      with coin toss randomization. At the test site, patients received SRP and laser
      treatment; at the contralateral control site, they received SRP treatment alone.
      RESULTS: Both treatment modalities resulted in significant improvements in all
      clinical and biochemical parameters. Sites irradiated with an 810 nm diode laser
      using the "hot tip" (~ 760  degrees C) technique showed enhanced healing in all
      the registered periodontal variables and interleukin (IL)-1beta levels, compared
      with SRP alone. CONCLUSIONS: Within the limitations of this study, the use of
      diode lasers as an adjunct to SRP produced significant improvements in clinical
      parameters as well as gingival crevicular fluid (GCF) IL-1beta levels in the 6
      month study period.

PMID- 24444429
TI  - Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane
      protein with an essential role in energy generation.
AB  - Non-proton pumping type II NADH dehydrogenase (NDH-2) plays a central role in the
      respiratory metabolism of bacteria, and in the mitochondria of fungi, plants and
      protists. The lack of NDH-2 in mammalian mitochondria and its essentiality in
      important bacterial pathogens suggests these enzymes may represent a potential
      new drug target to combat microbial pathogens. Here, we report the first crystal
      structure of a bacterial NDH-2 enzyme at 2.5 A resolution from Caldalkalibacillus
      thermarum. The NDH-2 structure reveals a homodimeric organization that has a
      unique dimer interface. NDH-2 is localized to the cytoplasmic membrane by two
      separated C-terminal membrane-anchoring regions that are essential for membrane
      localization and FAD binding, but not NDH-2 dimerization. Comparison of bacterial
      NDH-2 with the yeast NADH dehydrogenase (Ndi1) structure revealed non-overlapping
      binding sites for quinone and NADH in the bacterial enzyme. The bacterial NDH-2
      structure establishes a framework for the structure-based design of small
      molecule inhibitors. 

PMID- 24444430
TI  - Domestic abuse awareness and recognition among primary healthcare professionals
      and abused women: a qualitative investigation.
AB  - AIMS AND OBJECTIVES: To investigate the dynamics of domestic abuse awareness and
      recognition among primary healthcare professionals and abused women. BACKGROUND:
      Domestic abuse is a serious, public health issue that crosses geographical and
      demographic boundaries. Health professionals are well placed to recognise and
      respond to domestic abuse, but empirical evidence suggests that they are
      reluctant to broach the issue. Moreover, research has shown that women are
      reluctant to disclose abuse. DESIGN: A two-phase, qualitative study was conducted
      in Scotland. METHODS: Twenty-nine primary health professionals (midwives, health
      visitors and general practitioners) participated in the first phase of the study,
      and 14 abused women took part in phase two. Data were collected in 2011. Semi
      structured, individual interviews were conducted with the health professionals,
      and three focus groups were facilitated with the abused women. Data were analysed
      using a framework analysis approach. FINDINGS: Differing levels of awareness of
      the nature and existence of abuse are held by abused women and primary healthcare
      professionals. Specifically, many women do not identify their experiences as
      abusive. A conceptual representation of domestic abuse - the "abused women,
      awareness, recognition and empowerment' framework - arising from the study -
      presents a new way of capturing the complexity of the disclosure process.
      CONCLUSION: Further research is necessary to test and empirically validate the
      framework, but it has potential pedagogical use for the training and education of
      health professionals and clinical use with abused women. RELEVANCE TO CLINICAL
      PRACTICE: The framework may be used in clinical practice by nurses and other
      health professionals to facilitate open discussion between professionals and
      women. In turn, this may empower women to make choices regarding disclosure and
      safety planning.

PMID- 24444431
TI  - A four-step mechanism for the formation of supported-nanoparticle heterogenous
      catalysts in contact with solution: the conversion of Ir(1,5-COD)Cl/gamma-Al2O3
      to Ir(0)(~170)/gamma-Al2O3.
AB  - Product stoichiometry, particle-size defocusing, and kinetic evidence are
      reported consistent with and supportive of a four-step mechanism of supported
      transition-metal nanoparticle formation in contact with solution: slow continuous
      nucleation, A -> B (rate constant k1), autocatalytic surface growth, A + B -> 2B
      (rate constant k2), bimolecular agglomeration, B + B -> C (rate constant k3), and
      secondary autocatalytic surface growth, A + C -> 1.5C (rate constant k4), where A
      is nominally the Ir(1,5-COD)Cl/gamma-Al2O3 precursor, B the growing Ir(0)
      particles, and C the larger, catalytically active nanoparticles. The significance
      of this work is at least 4-fold: first, this is the first documentation of a four
      step mechanism for supported-nanoparticle formation in contact with solution.
      Second, the proposed four-step mechanism, which was obtained following the
      disproof of 18 alternative mechanisms, is a new four-step mechanism in which the
      new fourth step is A + C -> 1.5C in the presence of the solid, gamma-Al2O3
      support. Third, the four-step mechanism provides rare, precise chemical and
      kinetic precedent for metal particle nucleation, growth, and now agglomeration (B
      + B -> C) and secondary surface autocatalytic growth (A + C -> 1.5C) involved in
      supported-nanoparticle heterogeneous catalyst formation in contact with solution.
      Fourth, one now has firm, disproof-based chemical-mechanism precedent for two
      specific, balanced pseudoelementary kinetic steps and their precise chemical
      descriptors of bimolecular particle agglomeration, B + B -> C, and autocatalytic
      agglomeration, B + C -> 1.5C, involved in, for example, nanoparticle catalyst
      sintering. 

PMID- 24444432
TI  - Identity-by-descent genomic selection using selective and sparse genotyping.
AB  - BACKGROUND: Genomic selection methods require dense and widespread genotyping
      data, posing a particular challenge if both sexes are subject to intense
      selection (e.g., aquaculture species). This study focuses on alternative low-cost
      genomic selection methods (IBD-GS) that use selective genotyping with sparse
      marker panels to estimate identity-by-descent relationships through linkage
      analysis. Our aim was to evaluate the potential of these methods in selection
      programs for continuous traits measured on sibs of selection candidates in a
      typical aquaculture breeding population. METHODS: Phenotypic and genomic data
      were generated by stochastic simulation, assuming low to moderate heritabilities
      (0.10 to 0.30) for a Gaussian trait measured on sibs of the selection candidates
      in a typical aquaculture breeding population that consisted of 100 families (100
      training animals and 20 selection candidates per family). Low-density marker
      genotype data (~ 40 markers per Morgan) were used to trace genomic identity-by
      descent relationships. Genotyping was restricted to selection candidates from 30
      phenotypically top-ranking families and varying fractions of their phenotypically
      extreme training sibs. All phenotypes were included in the genetic analyses.
      Classical pedigree-based and IBD-GS models were compared based on realized
      genetic gain over one generation of selection. RESULTS: Genetic gain increased
      substantially (13 to 32%) with IBD-GS compared to classical selection and was
      greatest with higher heritability. Most of the extra gain from IBD-GS was
      obtained already by genotyping the 5% phenotypically most extreme sibs within the
      pre-selected families. Additional genotyping further increased genetic gains, but
      these were small when going from genotyping 20% of the extremes to all phenotyped
      sibs. The success of IBD-GS with sparse and selective genotyping can be explained
      by the fact that within-family haplotype blocks are accurately traced even with
      low-marker densities and that most of the within-family variance for normally
      distributed traits is captured by a small proportion of the phenotypically
      extreme sibs. CONCLUSIONS: IBD-GS was substantially more effective than classical
      selection, even when based on very few markers and combined with selective
      genotyping of small fractions of the population. The study shows that low-cost GS
      programs can be successful by combining sparse and selective genotyping with
      pedigree and linkage information.

PMID- 24444433
TI  - Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937.
AB  - INTRODUCTION: Methotrexate (MTX) has been for decades a standard treatment in a
      wide range of conditions, from malignancies to rheumatoid arthritis (RA). Despite
      this long experience, the mechanisms of action of MTX remain incompletely
      understood. Reported immunologic effects of MTX include induction of increased
      production of some cytokines, an effect that seems to be at odds with the
      generally anti-inflammatory effects of this drug in diseases like RA. To further
      elucidate these immune activities, we examined effects of MTX on the human
      monocytic cell line U937. METHODS: The U937 cell line was treated in vitro with
      pharmacologic-range concentrations of MTX and effects on production of
      interleukin (IL)-1, IL-6 and TNF alpha were measured. Changes in gene expression
      for IL-1 and IL-6 and specificities in the Jun-N-terminal kinase (JNK) signaling
      pathway including JNK 1, JNK2, JUN and FOS were also determined. The contribution
      of NF-kB, folate and adenosine pathways to the observed effects was determined by
      adding appropriate inhibitors to the MTX cultures. RESULTS: MTX mediated a dose
      dependent increase in IL-1 and IL-6 in U937 cells, as measured by secreted
      proteins and levels of gene expression. The increased cytokine expression was
      inhibited by addition of parthenolide and folinic acid, but not by caffeine and
      theophylline, suggesting that NF-kB and folates, but not adenosine, were involved
      in mediating the observed effects. When U937 cells were cultured with MTX,
      upregulated expression of JUN and FOS, but not JNK 1 or 2, also was observed.
      CONCLUSIONS: MTX induces expression of proinflammatory cytokines in U937
      monocytic cells. These effects might mediate the known toxicities of MTX
      including pneumonitis, mucositis and decreased bone mineral density.

PMID- 24444434
TI  - Diagnostic and prognostic value of tumor-associated trypsin inhibitor in
      gastrointestinal malignancies.

PMID- 24444435
TI  - Personality trait changes among young Finns: the role of life events and
      transitions.
AB  - Recent research has shown that personality traits continue to develop throughout
      the life span, but most profound changes are typically found during young
      adulthood. Increasing evidence suggests that life events play a significant role
      in many of these changes. The present longitudinal study examined the role of
      work, education, social, and health-related life events in the development of the
      Big Five traits among young Finns. Participants were originally recruited in 2004
      through elementary schools in a middle-sized Finnish city. Participants' Big Five
      traits and life events were measured via self-reports at ages 20 and 23 (Ns = 597
      and 588, respectively). Entering work life, beginning a relationship, and
      studying in university predicted increases in Conscientiousness, trying drugs
      predicted increases in Neuroticism, and onset of a chronic disease predicted
      increases in Neuroticism and Conscientiousness between ages 20 and 23. The
      results suggest that mature life transitions relate to stronger increases in
      Conscientiousness in young adulthood, and that non-normative life choices and
      events may predict increases in Neuroticism. 

PMID- 24444436
TI  - How do values shape technology design? An exploration of what makes the pursuit
      of health and wealth legitimate in academic spin-offs.
AB  - By actively supporting cooperation between academia, clinical settings and
      industry, several policy initiatives assume that the two policy agendas of health
      and wealth can be reconciled through the development of health technology. Our
      goal in this article is to shed light on the way the concurrent pursuit of health
      and wealth operates in practice by examining the valuation schemes, actions and
      decisions that shaped technology development in three Canadian spin-offs. Drawing
      on the sociology of judgement, our analytical framework conceives of technology
      development as a purposive collective action that unfolds in a normatively
      heterogeneous context (one pervaded with both corporate and public service
      mission values and norms). Our qualitative empirical analyses explore four
      valuation schemes and their corresponding regimes of engagement that characterise
      why and how technology developers commit themselves to addressing certain
      clinical, interactional, organisational and economic concerns throughout the
      development process. Our discussion suggests that the ability to reconcile health
      and wealth goals is to be found in the moral repertoires that provide meaning to,
      and render coherent technology developers' participation in corporate activities
      driven by economic growth. 

PMID- 24444437
TI  - Neuroprotective effects of propofol on ER stress-mediated apoptosis in
      neuroblastoma SH-SY5Y cells.
AB  - Anesthetic treatment has been associated with widespread apoptotic
      neurodegeneration in the neonatal rodent brain. It has recently been suggested
      that propofol, a short-acting intravenous anesthetic agent, may have a potential
      as a neuroprotective agent. An apoptotic pathway mediated through endoplasmic
      reticulum (ER) stress has been attracting attention. ER stress is associated with
      accumulation of unfolded or misfolded proteins in ER, and ER stress-induced
      apoptosis is implicated in a wide range of diseases, including
      ischemia/reperfusion injury, neurodegeneration, and diabetes. We investigated
      whether thapsigargin-induced ER stress is prevented by propofol in human
      neuroblastoma SH-SY5Y cells. SH-SY5Y cells were pretreated with various
      concentrations of propofol (1-10 MUM) for 3h before co-treatment with 0.5 MUM
      thapsigargin and propofol for 20 h. Levels of ssDNA, specific evidence of
      apoptosis, and biomarkers of ER stress (mRNA expression of Chop and sXbp-1) were
      determined. We also assayed calpain and caspase-4 activities and intracellular
      Ca(2+) ([Ca(2+)]i) levels. Thapsigargin-induced increases in ssDNA levels,
      expressions of ER stress biomarkers, activities of caspase-4 and calpain, and
      level of [Ca(2+)]i were suppressed by co-incubation with propofol. Our data
      indicate the possibility that propofol inhibits the Ca(2+) release from ER at
      clinically employed dose levels. These results demonstrate that propofol
      suppresses the ER stress-induced apoptosis in this cell system, and may have the
      neuroprotective potency. It may also be a promising agent for preventing damage
      from cerebral ischemia or edema.

PMID- 24444438
TI  - Hydrogen sulfide protected gastric epithelial cell from ischemia/reperfusion
      injury by Keap1 s-sulfhydration, MAPK dependent anti-apoptosis and NF-kappaB
      dependent anti-inflammation pathway.
AB  - Hydrogen sulfide (H2S) has been proposed as a novel gas-transmittter, which plays
      multiple physiological and pathological functions in various body systems,
      including gastrointestinal tract. The present study was undertaken to investigate
      the effects and mechanisms of H2S pharmacological preconditioning on gastric
      epithelial cells ischemia-reperfusion (I/R) injury. We report here that sodium
      hydrosulfide (NaHS), an H2S donor, concentration-dependently suppressed I/R
      induced cellular injury and apoptotic cell death. This protection effect was also
      confirmed by endogenous over-producing H2S. Furthermore, NaHS also prevented I/R
      induced oxidative stress and inflammatory responses, evidenced by increases in
      GSH level, decreases in MDA contents, reactive oxygen species generation and
      secretions of NO, IL-6 and TNF-alpha. NaHS also prevented I/R-induced p38- and c
      Jun NH2-terminal kinase (JNK)-mitogen-activated protein kinase (MAPK)
      phosphorylation and NF-kappaB activation. H2S also induced Keap1 s-sulfhydration,
      and further Keap1/Nrf2 disassociation and Nrf2 activation. H2S exerted its
      protective effect through reactive oxygen species clearance, inhibition of p38
      and JNK dependent cell apoptosis and NF-kappaB dependent inflammation pathway.
      Our results provide evidence that H2S may have potential therapeutic value in
      acute gastric mucosal lesion, which is often caused by ischemia/reperfusion. 

PMID- 24444440
TI  - Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated
      endothelium-dependent relaxation in rat mesenteric arteries.
AB  - Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial
      dysfunction in the initial stage of atherogenesis. The present study was designed
      to explore the underlying molecular mechanisms involved. Rat mesenteric arteries
      were organ cultured in the presence of different concentrations of ApoB or LDL.
      Vasodilation induced by acetylcholine was monitored by a sensitive myograph.
      Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and
      prostacyclin (PGI2) pathways were characterized by using specific pathway
      inhibitors. Real-time PCR and immunohistochemistry with confocal microscopy were
      used to examine alteration of mRNA and protein expressions for NO synthases (eNOS
      and iNOS) and cycloxygenase (COX), respectively. Lipid peroxidation was measured
      by thiobarbituric acid reactive substances. In the presence of either LDL or ApoB
      for 24h concentration-dependently attenuated the endothelium-dependent
      vasodilation. Immunohistochemistry staining of endothelial cell marker CD31 was
      weaker in the presence of LDL, indicating that LDL induced damage to the
      endothelium. Using the pathway specific inhibitors demonstrated that LDL-induced
      impairing vasodilation was mainly due to attenuation of NO pathway. This was
      supported by decreasing mRNA (real-time PCR) and protein expression
      (immunohistochemistry) for eNOS and iNOS, but not COX, in the presence of LDL. In
      addition, the levels of lipid peroxidation significantly increased in the
      presence of LDL for 24h. In conclusion, ApoB of LDL impairs vasodilation with
      damaging the endothelium and attenuating the NO-mediated endothelium-dependent
      relaxation, which might associate with lipid peroxidation and contribute to the
      development of cardiovascular disease. 

PMID- 24444439
TI  - Pharmacodynamic effects of atorvastatin versus rosuvastatin in coronary artery
      disease patients with normal platelet reactivity while on dual antiplatelet
      therapy--the PEARL randomized cross-over study.
AB  - High platelet reactivity during co-administration of clopidogrel and a CYP3A4
      metabolized statin (i.e. atorvastatin) can be lowered by switching to a non
      CYP3A4-metabolized statin (i.e rosuvastatin). Aim of this study was to verify if
      atorvastatin and rosuvastatin have different pharmacodynamic effects also when
      platelet reactivity while on dual antiplatelet therapy (DAPT) is normal at
      baseline. A total of 122 stable coronary artery disease patients receiving DAPT
      (clopidogrel 75 mg plus aspirin 100mg) who had evidence of normal platelet
      reactivity after a 1-week statin wash-out entered the trial. Patients were
      randomly assigned to atorvastatin (40 mg day, n=61) or rosuvastatin (20mg day,
      n=61) for 30 days. After another 1-week wash-out to avoid any carryover effect,
      cross-over was performed, and patients were switched to the other drug which was
      continued for 30 days. Platelet reactivity (expressed as P2Y(12) reaction units
      (PRU) by the VerifyNow assay [Accumetrics, San Diego, California]) was measured
      after 1-week statin wash-out and at the end of each treatment period. High
      platelet reactivity was defined as a PRU value >235. After 30-day atorvastatin,
      platelet reactivity did not significantly change as compared with pre-treatment
      evaluation (119 +/- 66 vs. 136 +/- 59 PRU, NS), with 2 patients only showing a
      PRU>235. Similarly, after 30-day rosuvastatin, platelet reactivity was unchanged
      vs. baseline (135 +/- 46 vs. 128 +/- 62 PRU, NS), with PRU>235 occurring in 3
      patients. Atorvastatin does not negatively affect DAPT as compared with
      rosuvastatin when is given to stable coronary artery disease patients with normal
      platelet reactivity while in statin wash-out (ClinicalTrials.gov Identifier:
      NCT01567774).

PMID- 24444441
TI  - Solasodine protects rat brain against ischemia/reperfusion injury through its
      antioxidant activity.
AB  - Ischemic stroke is the second leading cause of death worldwide. The major
      limitation of stroke management is the lack of clinically effective therapy.
      Antioxidants have been demonstrated as potent neuroprotective agents by enhancing
      the defense mechanism(s), whereas reducing the oxidative stress in the ischemic
      stroke models. In the present study, we evaluated neuroprotective potential of
      solasodine, an antioxidant glycoalkaloid of Solanum species, against global model
      of ischemia in rats. Ischemia/reperfusion (I/R)-injury produced marked elevation
      in lipid peroxidation (LPO) and nitric oxide (NO), whereas superoxide dismutase
      (SOD), catalase (CAT), and glutathione (GSH) levels were decreased in
      experimental animals. Prior administration of solasodine (100 and 200mg/kg, p.o.)
      significantly heightened SOD, CAT, GSH and total thiols, whereas reduced LPO and
      NO levels in the brain. Interestingly, brain coronal sectioning and
      histopathology studies revealed a marked reversal of I/R-provoked neuronal damage
      in the solasodine treatment groups. Taken together, our study, for the first
      time, demonstrates neuroprotective potential of solasodine against global
      ischemia-induced cerebral injury in experimental rats. We propose that the
      neuroprotection offered by solasodine could be attributed, at least in part, to
      its anti-oxidant property. 

PMID- 24444442
TI  - Lipopolysaccharide increases degradation of central monoamines: an in vivo
      microdialysis study in the nucleus accumbens and medial prefrontal cortex of
      mice.
AB  - Peripheral administration of lipopolysaccharide (LPS) in rodents induces
      anhedonia, i.e. the inability to experience pleasure. Recently, we reported that
      serotonin transporter (SERT) function is required for LPS-induced anhedonia. Less
      is known about the effect of LPS on the biological activity of dopamine
      transporters (DAT) and norepinephrine transporters (NET). Therefore, in vivo
      microdialysis was performed in the nucleus accumbens and medial prefrontal cortex
      of C57BL6/J mice exposed to saline or LPS (133 ug/kg i.p.). To investigate the
      possible involvement of different monoamine transporters, the triple reuptake
      inhibitor DOV 216,303 or saline was i.p. injected 30 min before the saline/LPS
      injection. The dose of LPS, shown to decrease responding for brain stimulation
      reward in mice, significantly increased extracellular levels of monoamine
      metabolites (5-HIAA, DOPAC and HVA) in the nucleus accumbens and medial
      prefrontal cortex. Remarkably, DOV 216,303 abolished LPS-induced DOPAC and HVA
      formation in the nucleus accumbens, suggesting that LPS increases DAT activity in
      this brain area. DOV 216,303 also inhibited LPS-induced DOPAC and HVA formation
      in the medial prefrontal cortex. Since DAT density is very low in this brain
      structure, reuptake of DA predominantly takes place via NET, suggesting that LPS
      increases DAT and NET activity in the medial prefrontal cortex. Furthermore, DOV
      216,303 pretreatment prevented LPS-induced 5-HIAA formation only in the medial
      prefrontal cortex, indicating that LPS increases prefrontal SERT activity. In
      conclusion, the present findings suggest that peripheral LPS increases DAT
      activity in the nucleus accumbens and increases NET and SERT activity in the
      medial prefrontal cortex of mice.

PMID- 24444443
TI  - The effects of LAA ligation on LAA electrical activity.
AB  - BACKGROUND: The arrhythmic role of the left atrial appendage (LAA) has been
      implicated in the maintenance of persistent atrial fibrillation. LAA isolation
      with catheter ablation has been successful but is limited by the risk of
      tamponade and electromechanical dissociation with the potential for LAA thrombus
      formation. OBJECTIVE: To assess whether LAA ligation results in LAA electrical
      isolation. METHODS: A total of 68 patients with contraindication or intolerance
      to oral anticoagulation therapy underwent LAA ligation with the LARIAT suture
      delivery device. Patients had unipolar [n = 30(44%)] or bipolar [n = 38(56%)]
      voltage measurements pre- and post-LAA ligation. RESULTS: All 68 patients
      underwent successful LAA ligation. There was a statistically significant
      reduction in the mean LAA voltage from pre-ligation (unipolar pre-ligation
      voltage 1.1 +/- 0.53 mV; bipolar pre-ligation voltage 4.7 +/- 2.83 mV) to post
      ligation (unipolar post-ligation voltage 0.3 +/- 0.38 mV; bipolar post-ligation
      voltage 0.6 +/- 0.27 mV). Ninety-four percent of the patients had a reduction in
      the LAA voltage after the closure of the snare, with 10 of 30 (33%) of the
      patients having complete elimination of LAA voltage with the initial tightening
      of the suture. Pacing from the LAA after the closure of the snare resulted in
      lack of capture of the left atrium in 28 of 31 patients. CONCLUSIONS: The snare
      closure of the LAA using the LARIAT device produces an acute reduction in the LAA
      voltage and inhibits the capture of the left atrium during LAA pacing. Future
      studies are needed to determine whether LAA ligation affects atrial fibrillation
      burden.

PMID- 24444444
TI  - Clinical predictors of adverse patient outcomes in an experience of more than
      5000 chronic endovascular pacemaker and defibrillator lead extractions.
AB  - BACKGROUND: It is difficult to predict adverse patient outcomes associated with
      transvenous lead extraction (TLE) procedures. OBJECTIVE: The purpose of this
      study was to examine the safety and efficacy of chronic endovascular pacemaker
      and implantable cardioverter-defibrillator (ICD) lead extraction and risk factors
      associated with adverse patient outcomes. METHODS: Consecutive patients
      undergoing TLE at the Cleveland Clinic between August 1996 and August 2011 were
      included in the analysis. Univariate and multivariable logistic regression
      analyses were performed to evaluate for associations with outcomes. Continuous
      data are given as median (25th, 75th percentile). Categorical data are given as
      number (percentage). RESULTS: In total, 5521 leads (4137 [74.9%] pacemaker, 1384
      [25.1%] ICD) were extracted during 2999 TLE procedures (patient age 67.2 [55.2,
      76.2] years, 30.2% female). Lead implant duration was 4.7 (2.4, 8.3) years, and
      2.0 (1.0, 2.0) leads were extracted per procedure. Powered sheaths were used in
      74.9% of procedures. Overall, there was 95.1% complete procedural success, 98.9%
      clinical success, and 1.1% failure, with 3.6% minor complications and 1.8% major
      complications. All-cause mortality within 30 days of TLE was 2.2%. Multivariable
      predictors of major complications included cerebrovascular disease, ejection
      fraction <=15%, lower platelet count, international normalized ratio >=1.2,
      mechanical sheaths, and powered sheaths. Multivariable predictors of all-cause
      mortality within 30 days of TLE included body mass index <25 kg/m(2), end-stage
      renal disease, higher New York Heart Association functional class, lower
      hemoglobin, higher international normalized ratio, lead extraction for infection,
      and extraction of a dual-coil ICD lead. CONCLUSION: TLE in this single-center
      experience was highly successful. Risk factors associated with adverse patient
      outcomes were identified.

PMID- 24444445
TI  - Relations between circulating microRNAs and atrial fibrillation: data from the
      Framingham Offspring Study.
AB  - BACKGROUND: MicroRNA (miRNA) expression in atrial tissue has been implicated in
      pathologic susceptibility to atrial fibrillation (AF). Nevertheless, data on how
      circulating levels relate to AF are limited. OBJECTIVE: The purpose of this study
      was to test the hypothesis that circulating miRNAs are associated with AF.
      METHODS: Among 2445 Framingham Heart Study Offspring participants, we measured
      the expression of 385 circulating whole blood miRNAs by high-throughput
      quantitative reverse transcriptase polymerase chain reaction. We related miRNA
      levels with prevalent and new-onset AF. RESULTS: Mean age of the cohort was 66.3
      +/- 8.9 years, and 56% were women; 153 participants had clinically apparent AF at
      baseline, and 107 developed AF during median follow-up of 5.4 years. miRNA-328
      (miR-328) expression was lower among participants with prevalent AF (8.76 cycle
      threshold) compared to individuals with no AF (7.75 cycle threshold, P <.001).
      The association between miR-328 and prevalent AF persisted after adjustment for
      age, sex, and technical covariates (odds ratio 1.21, P = 1.8 * 10(-4)) but was
      attenuated in analyses adjusting for clinical AF risk factors (odds ratio 1.14, P
      = .017). In contrast to the associations between miR-328 and prevalent AF, none
      of the circulating miRNAs were associated with incident AF. CONCLUSION:
      Circulating levels of miR-328, a miRNA known to promote atrial electrical
      remodeling by reducing L-type Ca(2+) channel density, were associated with
      prevalent AF. Adjustment for risk factors that promote atrial remodeling,
      including hypertension, attenuated the association between miR-328 and AF,
      potentially implicating miR-328 as a potential mediator of atrial remodeling and
      AF vulnerability.

PMID- 24444446
TI  - Association of CASQ2 polymorphisms with sudden cardiac arrest and heart failure
      in patients with coronary artery disease.
AB  - BACKGROUND: Abnormal calcium handling plays a crucial role in arrhythmias, sudden
      cardiac arrest (SCA), and congestive heart failure (CHF). Calsequestrin 2 (CASQ2)
      mutations affect calcium release and initiate malignant ventricular arrhythmias
      (VAs) and SCA syndromes. Common single nucleotide polymorphisms (SNPs) in CASQ2
      may be associated with SCA in patients with coronary artery disease (CAD).
      OBJECTIVE: The purpose of this study was to examine the association of common
      CASQ2 SNPs with the risk of SCA in patients with CAD. METHODS: CASQ2 SNPs (n =
      14) were genotyped and analyzed in a case control study comparing 114 patients
      with CAD and SCA due to VA to 311 CAD controls without VA or SCA. RESULTS:
      Multivariate logistic regression adjusting for age and CHF status identified an
      association between rs7521023 with SCA (odds ratio [OR] 2.72, 95% confidence
      interval [CI] 1.44-5.13, P = .002). The substantial impact of CHF on SCA in the
      model (OR 26.6, 95% CI 13.40-52.70, P <.001) led us to further examine the
      relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants
      (rs7521023: OR 0.4, 95% CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 95% CI 3.63
      108.2, P <.001) associated with CHF after adjusting for SCA, age, gender, and
      hypertension. CONCLUSION: We observed association between a CASQ2 polymorphism
      and SCA due to VA in patients with CAD adjusting for CHF and independent
      associations between CASQ2 SNPs and CHF adjusting for SCA. Further investigation
      in independent cohorts is needed to confirm these findings.

PMID- 24444447
TI  - Structural studies of adipokinetic hormones in water and DPC micelle solution
      using NMR distance restrained molecular dynamics.
AB  - Melme-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp amide) and Declu-CC (pGlu-Leu-Asn-Phe
      Ser-Pro-Asn-Trp-Gly-Asn amide) are members of the insect adipokinetic hormone
      family with very different activities in the locust bioassay. The conformations
      of both peptides were determined in water and in a phospholipid (DPC) micelle
      solution using nuclear magnetic resonance (NMR) restrained molecular dynamics
      simulations. In water, Melme-CC has one dominant conformation while in DPC
      solution it has two preferred conformation. In water, Declu-CC has two
      conformations but in DPC solution it has one preferred conformation, which is
      similar to one of the water conformations. All the conformations have type IV
      beta-turn between residues 4 and 7. The binding of the two peptides to the DPC
      micelle is different. Melme-CC does not bind strongly to the surface and is
      oriented with the beta-turn facing the surface. Declu-CC interacts more strongly
      with the beta-turn facing away from the surface. Both termini having hydrophobic
      interactions with the surface. In Declu-CC the side chain of Asn(7) projects away
      from the chain while in Melme-CC the Asp(7) side chain is folded inside the
      chain. The different orientation of these side chains may account for the much
      higher biological activity of Declu-CC in mobilizing lipids in the locust
      compared to the poor biological effect of Melme-CC in this bioassay. Receptor
      binding of Declu-CC was tested using a model AKH receptor from Anopheles gambiae.
      A free energy of binding of -38.5 kJ mol(-1) was found.

PMID- 24444448
TI  - Oxidative damage in keratinocytes exposed to cigarette smoke and aldehydes.
AB  - Cigarette smoke (CS) is a significant environmental source of human exposure to
      chemically active saturated (acetaldehyde) and alpha,beta-unsaturated aldehydes
      (acrolein) inducing protein carbonylation and dysfunction. The exposure of oral
      tissues to environmental hazards is immense, especially in smokers. The
      objectives of the current study were to examine the effect of aldehydes
      originating from CS on intracellular proteins of oral keratinocytes and to
      observe the antioxidant response in these cells. Intracellular protein carbonyl
      modification under CS, acrolein and acetaldehyde exposure in the HaCaT
      keratinocyte cell line, representing oral keratinocytes was examined by Western
      blot. Possible intracellular enzymatic dysfunction under the above conditions was
      examined by lactate dehydrogenase (LDH) activity assay. Oxidative stress response
      was investigated, by DCF (2,7-dichlorodihydrofluorescein) assay and GSH
      (glutathione) oxidation. Intracellular protein carbonyls increased 5.2 times
      after CS exposure and 2.7 times after exposure to 1 MUmol of acrolein. DCF assay
      revealed an increase of fluorescence intensity 3.2 and 3.1 times after CS and
      acrolein exposure, respectively. CS caused a 72.5% decrease in intracellular GSH
      levels compared to controls. Activity of intracellular LDH was preserved.
      alpha,beta-Unsaturated aldehydes from CS are capable of intracellular protein
      carbonylation and have a role in intracellular oxidative stress elevation in
      keratinocytes, probably due to the reduction in GSH levels.

PMID- 24444449
TI  - Skin sensitization risk assessment model using artificial neural network analysis
      of data from multiple in vitro assays.
AB  - The sensitizing potential of chemicals is usually identified and characterized
      using in vivo methods such as the murine local lymph node assay (LLNA). Due to
      regulatory constraints and ethical concerns, alternatives to animal testing are
      needed to predict skin sensitization potential of chemicals. For this purpose,
      combined evaluation using multiple in vitro and in silico parameters that reflect
      different aspects of the sensitization process seems promising. We previously
      reported that LLNA thresholds could be well predicted by using an artificial
      neural network (ANN) model, designated iSENS ver.1 (integrating in vitro
      sensitization tests version 1), to analyze data obtained from two in vitro tests:
      the human Cell Line Activation Test (h-CLAT) and the SH test. Here, we present a
      more advanced ANN model, iSENS ver.2, which additionally utilizes the results of
      antioxidant response element (ARE) assay and the octanol-water partition
      coefficient (LogP, reflecting lipid solubility and skin absorption). We found a
      good correlation between predicted LLNA thresholds calculated by iSENS ver.2 and
      reported values. The predictive performance of iSENS ver.2 was superior to that
      of iSENS ver.1. We conclude that ANN analysis of data from multiple in vitro
      assays is a useful approach for risk assessment of chemicals for skin
      sensitization. 

PMID- 24444450
TI  - Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell
      lines.
AB  - This study aimed to evaluate the acrylamide (ACR)-induced apoptotic effects on
      rat primary astrocytes and three human astrocytoma-derived cell lines (U-1240 MG,
      U-87 MG, and U-251 MG). As determined through the MTT assay, treatment with 1 and
      2 mM ACR for 24-72 h resulted in decreased cell viability in all cells. Decreases
      in cell viability could be blocked in all cells with the exception of U-251 MG
      cells by Z-DEVD FMK. ACR-induced dose-dependent apoptotic effects were also
      demonstrated by increases in the sub-G1 phase cell population in all cells. The
      decreased expressions of pro-caspase 3, 8, and 9 and the interruption of the
      mitochondrial membrane potential were observed in all cells. Exposure to 2 mM ACR
      for 48 h resulted in increased Bax/Bcl-2 ratios in primary astrocytes and U-87 MG
      cells, whereas the overexpression of Bcl-2 was observed in U-1240 MG and U-251 MG
      cells. The ACR-induced increases in the levels of p53 and pp53 in primary
      astrocytes could be attenuated by caffeine. These results suggest the existence
      of a common apoptotic pathway among all cell types and that U-87 MG cells may be
      a suitable substitute in vitro model for primary astrocytes in future studies on
      ACR-induced neurotoxicity.

PMID- 24444451
TI  - The effect of programs to improve oral hygiene outcomes for older residents in
      long-term care: a systematic review.
AB  - Nurses have a critical role in promoting oral health in dependent older adults
      residing in long-term care or having extended hospital stays. Strategies aimed at
      improving the quality of oral hygiene care nurses provide may contribute to
      better oral hygiene outcomes. The purpose of this systematic review was to
      examine the effect of intervention programs designed to enhance the ability of
      nurses or those to whom they delegate care to improve oral hygiene outcomes in
      frail older adults. Studies reported an educational program, either alone or
      augmented in some way. The study interventions consisted of: (a) single in
      service education sessions; (b) single in-service education sessions supplemented
      by a "train-the-trainer" approach; and (c) education sessions supplemented with
      ongoing active involvement of a dental hygienist. None of the approaches emerged
      as being desirable over the others, as methodologically strong studies with good
      intervention integrity were lacking, and a variety of oral health outcomes were
      used to measure effectiveness of the interventions, making comparisons across
      studies difficult.

PMID- 24444452
TI  - Social activity decreases risk of placement in a long-term care facility for a
      prospective sample of community-dwelling older adults.
AB  - The purpose of this study was to determine the role of modifiable factors in the
      risk of long-term care (LTC) placement. Using data from a cohort of community
      residing older adults (N = 189), a secondary analysis was conducted of the
      contribution of social activity, sleep disturbances, and depressive symptoms to
      the risk of LTC placement. Analyses controlled for cognitive and functional
      impairment, age, and medical conditions. Within 5 years, 20% of participants were
      placed in a LTC facility. Each unit increase in social activity was associated
      with a 24% decrease in the risk of placement (odds ratio [OR] = 0.763, p = 0.001,
      95% confidence interval [CI] [0.65, 0.89]). Cognitive impairment (OR = 3.05, p =
      0.017, 95% CI [1.23, 7.59]), medical conditions (OR = 1.22, p = 0.039, 95% CI
      [1.01, 1.47]), and age (OR = 1.101, p = 0.030, 95% CI [1.01, 1.20]) were also
      significant individual predictors of placement. Although many of the strongest
      risk factors for placement are not modifiable, older adults who engage in more
      social activity outside the home may be able to delay transition from independent
      living.

PMID- 24444453
TI  - Results and lessons learned from a nurse practitioner-guided dementia care
      intervention for primary care patients and their family caregivers.
AB  - Older adults with dementia care needs often visit primary care physicians (PCPs),
      but PCP dementia care limitations are widely documented. This study tested the
      value of employing a nurse practitioner (NP) with geropsychiatric expertise to
      augment PCP care for newly and recently diagnosed patients and family caregivers.
      Twenty-one dyads received the NP intervention; 10 dyads were controls. Outcomes
      included patient neuropsychiatric symptom and quality of life changes, and
      caregiver depression, burden, and self-efficacy changes. Intervention
      acceptability by patients, caregivers, and PCPs was determined. No outcome
      differences were found; however, the NP intervention was deemed highly
      satisfactory by all stakeholders. Patients experienced no significant cognitive
      decline during the 12-month study period, helping explain why outcomes did not
      change. Given widespread acceptability, future tests of this PCP-enhancing
      intervention should include patients with more progressive cognitive decline at
      study entry. NPs with geropsychiatric expertise are ideal interventionists for
      this rapidly growing target population.

PMID- 24444454
TI  - Assigning the EPR fine structure parameters of the Mn(II) centers in Bacillus
      subtilis oxalate decarboxylase by site-directed mutagenesis and DFT/MM
      calculations.
AB  - Oxalate decarboxylase (OxDC) catalyzes the Mn-dependent conversion of the oxalate
      monoanion into CO2 and formate. EPR-based strategies for investigating the
      catalytic mechanism of decarboxylation are complicated by the difficulty of
      assigning the signals associated with the two Mn(II) centers located in the N-
      and C-terminal cupin domains of the enzyme. We now report a mutational strategy
      that has established the assignment of EPR fine structure parameters to each of
      these Mn(II) centers at pH 8.5. These experimental findings are also used to
      assess the performance of a multistep strategy for calculating the zero-field
      splitting parameters of protein-bound Mn(II) ions. Despite the known sensitivity
      of calculated D and E values to the computational approach, we demonstrate that
      good estimates of these parameters can be obtained using cluster models taken
      from carefully optimized DFT/MM structures. Overall, our results provide new
      insights into the strengths and limitations of theoretical methods for
      understanding electronic properties of protein-bound Mn(II) ions, thereby setting
      the stage for future EPR studies on the electronic properties of the Mn(II)
      centers in OxDC and site-specific variants. 

PMID- 24444455
TI  - Mn accumulation and tolerance in Celosia argentea Linn.: a new Mn
      hyperaccumulating plant species.
AB  - Identifying a hyperaccumulator is an important groundwork for the phytoextraction
      of heavy metal-contaminated soil. Celosia argentea Linn., which grew on a Mn
      tailing wasteland, was found to hyperaccumulate Mn (14 362mgkg(-1) in leaf dry
      matter) in this study. To investigate Mn tolerance and accumulation in C.
      argentea, a hydroponic culture experiment was conducted in a greenhouse. Results
      showed that the biomass and the relative growth rate of C. argentea were
      insignificantly different (p>0.05) at the Mn supply level ranging from 2.5mgL(-1)
      (control) to 400mgL(-1). Manganese concentrations in leaves, stems, and roots
      reached maxima of 20228, 8872, and 2823mgkg(-1) at 600mgMnL(-1), respectively.
      The relative rate of Mn accumulation increased by 91.2% at 400mgMnL(-1). Over 95%
      of the total Mn taken up by C. argentea was translocated to shoots. Thus, C.
      argentea exhibits the basic characteristics of a Mn-hyperaccumulator. This
      species has great potential to remediate Mn-contaminated soil cheaply and can
      also aid the studies of Mn uptake, translocation, speciation, distribution and
      detoxification in plants. 

PMID- 24444456
TI  - Modified composites based on mesostructured iron oxyhydroxide and synthetic
      minerals: a potential material for the treatment of various toxic heavy metals
      and its toxicity.
AB  - The composites of mesostructured iron oxyhydroxide and/or commercial synthetic
      zeolite were investigated for use in the removal of toxic heavy metals, such as
      cadmium, copper, lead and arsenic, from aqueous solution. Four types of
      adsorbents, dried alginate beads (DABs), synthetic-zeolite impregnated beads
      (SZIBs), meso-iron-oxyhydroxide impregnated beads (MIOIBs) and synthetic
      zeolite/meso-iron-oxyhydroxide composite beads (SZMIOIBs), were prepared for
      heavy metal adsorption tests. Laboratory experiments were conducted to
      investigate the removal efficiencies of cations and anions of heavy metals and
      the possibility of regenerating the adsorbents. Among these adsorbents, the
      MIOIBs can simultaneously remove cations and anions of heavy metals; they have
      high adsorption capacities for lead (60.1mgg(-1)) and arsenic (71.9mgg(-1))
      compared with other adsorbents, such as DABs (158.1 and 0.0mgg(-1)), SZIB (42.9
      and 0.0mgg(-1)) and SZMIOIB (54.0 and 5.9mgg(-1)) for lead and arsenic,
      respectively. Additionally, the removal efficiency was consistent at
      approximately 90%, notwithstanding repetitive regeneration. The characteristics
      of meso-iron-oxyhydroxide powder were confirmed by X-ray diffraction, Brunauer
      Emmett-Teller and transmission electron microscopy. We also performed a
      comparative toxicity study that indicated that much lower concentrations of the
      powdered form of mesostructured iron oxyhydroxide had stronger cytotoxicity than
      the granular form. These results suggest that the granular form of meso iron
      oxyhydroxide is a more useful and safer adsorbent for heavy metal treatment than
      the powdered form. This research provides promising results for the application
      of MIOIBs as an adsorbent for various heavy metals from wastewater and sewage. 

PMID- 24444457
TI  - Insight into the contribution of individual functional groups to the flash point
      of organic compounds.
AB  - Flash point temperatures of organic compounds are predicted on the basis of a
      power law involving 21 additive contributions associated with non-hydrogen atoms
      and ring structures. The model is parametrized against a previous data set of 287
      simple organic molecules. An average absolute error of 8.6K and a maximal error
      of about 50K are obtained when applying this model to an external test set of 488
      compounds within its applicability domain. The overall performances of the method
      are remarkable given its simplicity and the small number of parameters involved.
      In addition, the present work provides valuable insight into the influence of
      individual functional groups to flash point temperatures. 

PMID- 24444458
TI  - Individual differences in commitment to value-based beliefs and the amplification
      of perceived belief dissimilarity effects.
AB  - The commitment to beliefs (CTB) framework (Maxwell-Smith & Esses, 2012) proposes
      that there are individual differences in the extent to which people generally
      follow beliefs that are a reflection of their values. The current research
      hypothesized that CTB would amplify the effects of perceived belief dissimilarity
      or incompatibility, such that individuals higher in CTB would display more
      pronounced reactions to belief-relevant groups, events, or individuals seen as
      incompatible with their value-based beliefs. We tested our hypothesis in three
      studies that assessed participants' CTB and their perceptions of belief
      dissimilarity or incompatibility with regard to other religious groups (Study 1),
      political parties during a national election (Study 2), and their romantic
      partner (Study 3). CTB amplified the effects of perceived belief dissimilarity or
      incompatibility on people's biases toward other religious groups, voting
      intentions and behavior in a national election, and their evaluative and
      behavioral responses toward their romantic partner. These results collectively
      suggest that perceptions of belief dissimilarity or incompatibility are
      particularly important cues for individuals with higher levels of CTB as they
      encounter other people or events that are relevant to their beliefs. 

PMID- 24444459
TI  - BioShell-Threading: versatile Monte Carlo package for protein 3D threading.
AB  - BACKGROUND: The comparative modeling approach to protein structure prediction
      inherently relies on a template structure. Before building a model such a
      template protein has to be found and aligned with the query sequence. Any error
      made on this stage may dramatically affects the quality of result. There is a
      need, therefore, to develop accurate and sensitive alignment protocols. RESULTS:
      BioShell threading software is a versatile tool for aligning protein structures,
      protein sequences or sequence profiles and query sequences to a template
      structures. The software is also capable of sub-optimal alignment generation. It
      can be executed as an application from the UNIX command line, or as a set of Java
      classes called from a script or a Java application. The implemented Monte Carlo
      search engine greatly facilitates the development and benchmarking of new
      alignment scoring schemes even when the functions exhibit non-deterministic
      polynomial-time complexity. CONCLUSIONS: Numerical experiments indicate that the
      new threading application offers template detection abilities and provides much
      better alignments than other methods. The package along with documentation and
      examples is available at: http://bioshell.pl/threading3d.

PMID- 24444460
TI  - An interactive Bayesian model for prediction of lymph node ratio and survival in
      pancreatic cancer patients.
AB  - BACKGROUND: Regional lymph node status has long been used as a dichotomous
      predictor of clinical outcomes in cancer patients. More recently, interest has
      turned to the prognostic utility of lymph node ratio (LNR), quantified as the
      proportion of positive nodes examined. However, statistical tools for the joint
      modeling of LNR and its effect on cancer survival are lacking. METHODS: Data were
      obtained from the NCI SEER cancer registry on 6400 patients diagnosed with
      pancreatic ductal adenocarcinoma from 2004 to 2010 and who underwent radical
      oncologic resection. A novel Bayesian statistical approach was developed and
      applied to model simultaneously patients' true, but unobservable, LNR statuses
      and overall survival. New web development tools were then employed to create an
      interactive web application for individualized patient prediction. RESULTS:
      Histologic grade and T and M stages were important predictors of LNR status.
      Significant predictors of survival included age, gender, marital status, grade,
      histology, T and M stages, tumor size, and radiation therapy. LNR was found to
      have a highly significant, non-linear effect on survival. Furthermore, predictive
      performance of the survival model compared favorably to those from studies with
      more homogeneous patients and individualized predictors. CONCLUSIONS: We provide
      a new approach and tool set for the prediction of LNR and survival that are
      generally applicable to a host of cancer types, including breast, colon,
      melanoma, and stomach. Our methods are illustrated with the development of a
      validated model and web applications for the prediction of survival in a large
      set of pancreatic cancer patients.

PMID- 24444461
TI  - Doctors should care for people who choose to die by starvation, says Dutch
      Medical Association.

PMID- 24444462
TI  - Air-stable gold nanoparticles ligated by secondary phosphine oxides for the
      chemoselective hydrogenation of aldehydes: crucial role of the ligand.
AB  - The synthesis of air-stable and homogeneous gold nanoparticles (AuNPs) employing
      tert-butyl(naphthalen-1-yl)phosphine oxide as supporting ligand is described via
      NaBH4 reduction of a Au(I) precursor, [(tert-butyl(naphthalen-1-yl)phosphine
      oxide)AuCl]2. This highly reproducible and simple procedure furnishes small (1.24
      +/- 0.16 nm), highly soluble nanoparticles that are found to be highly active
      catalysts for the hydrogenation of substituted aldehydes, giving high conversions
      and chemoselectivities for a wide variety of substrates. In addition to catalytic
      studies the role of the novel stabilizer in the remarkable activity and
      selectivity exhibited by this system was interrogated thoroughly using a wide
      range of techniques, including ATR FT-IR, HRMAS NMR, XPS, and EDX spectroscopy.
      In particular, isotopic labeling experiments enabled us to probe the coordination
      mode adopted by the SPO ligand bound to the nanoparticle surface by ATR FT-IR
      spectroscopy. In combination with a series of control experiments we speculate
      that the SPO ligand demonstrates ligand-metal cooperative effects and plays a
      seminal role in the heterolytic hydrogenation mechanism. 

PMID- 24444463
TI  - Tissue identity testing of cancer by short tandem repeat polymorphism: pitfalls
      of interpretation in the presence of microsatellite instability.
AB  - Tissue identity testing by short tandem repeat (STR) polymorphism offers
      discriminating power in resolving tissue mix-up or contamination. However, one
      caveat is the presence of microsatellite unstable tumors, in which genetic
      alterations may drastically change the STR wild-type polymorphism leading to
      unexpected allelic discordance. We examined how tissue identity testing results
      can be altered by the presence of microsatellite instability (MSI). Eleven cases
      of MSI-unstable (9 intestinal and 2 endometrial adenocarcinomas) and 10 cases of
      MSI-stable tumors (all colorectal adenocarcinomas) were included. All had been
      previously tested by polymerase chain reaction testing at 5 National Cancer
      Institute (NCI) recommended MSI loci and/or immunohistochemistry for DNA mismatch
      repair proteins (MLH1, MSH2, MSH6, and PMS2). Tissue identity testing targeting
      15 STR loci was performed using AmpF/STR Identifiler Amplification. Ten of 11 MSI
      unstable tumors demonstrated novel alleles at 5 to 12 STR loci per case and
      frequently with 3 or more allelic peaks. However, all affected loci showed
      identifiable germline allele(s) in MSI-high tumors. A wild-type allelic profile
      was seen in 7 of 10 MSI-stable tumors. In the remaining 3 cases, isolated novel
      alleles were present at a unique single locus in addition to germline alleles.
      Loss of heterozygosity was observed frequently in both MSI-stable (6/11 cases)
      and MSI-unstable tumors (8/10 cases). In conclusion, MSI may significantly alter
      the wild-type allelic polymorphism, leading to potential interpretation errors of
      STR genotyping. Careful examination of the STR allelic pattern, high index of
      suspicion, and follow-up MSI testing are crucial to avoid erroneous conclusions
      and subsequent clinical and legal consequences. 

PMID- 24444464
TI  - A PIK3CA mutation detected in plasma from a patient with synchronous primary
      breast and lung cancers.
AB  - Digital polymerase chain reaction is a new technology that enables detection and
      quantification of cancer DNA molecules from peripheral blood. Using this
      technique, we identified mutant PIK3CA DNA in circulating ptDNA (plasma tumor
      DNA) from a patient with concurrent early stage breast cancer and non-small cell
      lung cancer. The patient underwent successful resection of both her breast and
      lung cancers, and using standard Sanger sequencing the breast cancer was shown to
      harbor the identical PIK3CA mutation identified in peripheral blood. This case
      report highlights potential applications and concerns that can arise with the use
      of ptDNA in clinical oncology practice. 

PMID- 24444465
TI  - High-resolution melting analysis is a sensitive diagnostic tool to detect
      imatinib-resistant and imatinib-sensitive PDGFRA exon 18 mutations in
      gastrointestinal stromal tumors.
AB  - The mutational status of KIT and PDGFRA is highly relevant for prognosis and
      therapy prediction in gastrointestinal stromal tumors (GIST). PDGFRA exon 18
      mutations have direct therapeutic implications since it is crucial to distinguish
      mutations associated with sensitivity to tyrosine kinase inhibitors from those
      causing primary resistance, eg, the most common exon 18 mutation p.D842V. In
      response to a growing demand for reliable, faster and more sensitive methods we
      established and validated a high-resolution melting (HRM) assay for PDGFRA exon
      18. A total of 159 GIST samples were comparatively analyzed by HRM and direct
      Sanger sequencing. We demonstrate that HRM provides highly reliable mutational
      results with higher sensitivity and shorter time to diagnosis compared to Sanger
      sequencing. We determined the sensitivity threshold of HRM at 6% of mutated
      alleles. PDGFRA exon 18 wild-type status and the most common p.D842V resistance
      mutation (together representing >90% of the cases) can be detected specifically
      by HRM. Other rare mutations can be pre-screened by HRM and afterwards determined
      precisely by DNA sequencing. In this way we detected four novel mutations in
      PDGFRA exon 18, two of which were associated with an aggressive clinical course.
      Including these new mutations, we provide a comprehensive overview of all 60
      currently known subtypes of PDGFRA exon 18 mutations in GIST. Seven of them
      (accounting for about 75% of all exon 18-mutated GISTs) are reported to be
      resistant to imatinib. However, there are at least 10 other mutations which are
      regarded as sensitive to tyrosine kinase inhibitors. 

PMID- 24444467
TI  - Non-mass-associated intraductal papillomas: is excision necessary?
AB  - Intraductal papillomas (IDPs) of the breast can be associated with a variety of
      clinical symptoms and radiologic findings. Surgical excision is often recommended
      based on the possibility of an associated high-grade lesion. Although the rate of
      upgrades has been extensively evaluated for IDPs, many studies are hindered by
      broad inclusion criteria, a lack of pathologic-radiologic concordance, and no
      standard definition of what constitutes an upgrade. In the current study, we
      evaluate the risk of upgrade for a specific subset of IDPs: non-mass-associated
      IDPs. We identified all breast needle core biopsies with a diagnosis of IDP
      between 2003 and 2010. Patients with associated masses, architectural distortion,
      or ipsilateral breast cancer were excluded. All needle core biopsy slides and
      relevant imaging studies were reviewed to ensure pathologic-radiologic
      concordance. Excision pathology was also reviewed; an upgrade was defined as the
      presence of ductal carcinoma in situ or invasive carcinoma in the excision.
      Seventy-nine IDPs that met inclusion criteria were identified and were further
      divided into 3 histologic categories: micropapilloma, fragmented IDP, and
      atypical IDP. Micropapillomas and fragmented IDPs had no upgrades (0/37). In
      patients who did not undergo excision, none subsequently developed ipsilateral
      breast cancer (follow-up, 50-61 months). This is in contrast to atypical IDPs
      that had a 33% upgrade rate. One patient with an unexcised atypical IDP developed
      ipsilateral breast cancer within 2 years. Our data suggest that conservative
      follow-up is reasonable for non-mass-associated IDPs without atypia regardless of
      microscopic size, provided that careful pathologic-radiologic correlation is
      achieved. 

PMID- 24444466
TI  - CD79B and MYD88 mutations in diffuse large B-cell lymphoma.
AB  - Mutations in 2 upstream components of the nuclear factor kappaB (NF-kappaB)
      pathway, CD79B and MYD88, are important information for new target therapy in
      malignant lymphoma. We examined the prevalence and clinicopathologic
      characteristics of CD79B and MYD88 mutation in a cohort of Asian diffuse large B
      cell lymphoma (DLBCL) patients. CD79B and MYD88 mutations were analyzed by Sanger
      sequencing in 187 DLBCL tissue samples. CD79B immunoreceptor tyrosine-based
      activation motif spanning exon 5 and 6 and MYD88 TIR domain spanning exons 3, 4
      and 5 were amplified and sequenced. The cell-of-origin was determined based on
      immunohistochemical stains for CD10, BCL-6 and MUM-1 by Hans' algorithm. CD79B
      was mutated in 16 cases (8.5%), mostly involving the first tyrosine (Y196) of
      immunoreceptor tyrosine-based activation motif. For MYD88, L265P mutation was
      found in 31 cases (out of 161, 19.3%). In 11 of these, a CD79B mutation
      coexisted, which constituted 69% of CD79B mutants and 36% of MYD88 L265P cases.
      Clinicopathologic comparison between the mutant and the wild-type group showed
      that the mean age was older for both CD79B (66 versus 58 years) and MYD88 L265P
      mutant groups (64 versus 58 years). Survival analyses showed that neither CD79B
      mutation nor MYD88 L265P was a significant prognostic indicator. In conclusion,
      CD79B and MYD88 mutations are associated with an older age at onset in DLBCL with
      a significant overlap, which did not affect the outcome of the disease. 

PMID- 24444468
TI  - The prognostic significance of vasohibin 1-associated angiogenesis in patients
      with hepatocellular carcinoma.
AB  - Vasohibin 1, an endothelium-derived negative feedback regulator of angiogenesis,
      is induced by fibroblast growth factor 2 (FGF-2) and vascular endothelial growth
      factor A (VEGF-A). In this study, we retrospectively evaluated immunoreactivity
      of FGF-2 and VEGF-A as well as microvessel density (MVD) determined by expression
      of vasohibin 1 and CD34 (MVD-CD34) and correlated the findings with clinical
      outcomes of 181 patients with hepatocellular carcinoma (HCC). Double
      immunostaining of an endothelial marker CD34 and vasohibin 1 with Ki-67 was also
      performed to assess angiogenic activity of endothelial cells in HCC. The ratio of
      Ki-67-positive endothelial cells in vasohibin 1-positive vessels (22%) was
      significantly higher than that of CD34-positive vessels (9%, P < .001),
      suggesting the correlation between vasohibin 1 and neovascularization in
      endothelial cells of HCC. MVD-CD34 decreased, but the ratio of MVD determined by
      expression of vasohibin 1 to MVD-CD34 (vasohibin 1/CD34) increased significantly
      according to histologic grade. Vasohibin 1 was significantly correlated with the
      status of FGF-2 (P = .007) but not with that of VEGF-A (P = .055). The 10-year
      overall survival and the 2-year disease-free survival rates of the low vasohibin
      1/CD34 group (vasohibin 1/CD34 <=0.459) were significantly higher than those of
      the high vasohibin 1/CD34 group (vasohibin 1/CD34 >0.459) (survival, 48% versus
      38% and 52% versus 35%; P < .001 and P < .05, respectively). In addition,
      vasohibin 1/CD34 in HCC patients was an independent marker of poor prognosis, as
      determined by multivariate analysis (risk ratio, 1.973; 95% confidence interval,
      1.049-3.711; P = .035). Vasohibin 1/CD34 could identify the proliferative vessels
      and could be a useful biomarker for predicting the clinical outcome of HCC
      patients. 

PMID- 24444469
TI  - Stanford University Network for Diagnosis of Retinopathy of Prematurity
      (SUNDROP): five years of screening with telemedicine.
AB  - BACKGROUND AND OBJECTIVE: To report the 5-year results of the Stanford University
      Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine
      initiative. PATIENTS AND METHODS: Infants requiring retinopathy of prematurity
      (ROP) screening at six neonatal intensive care units from December 1, 2005, to
      November 30, 2010, were evaluated with remote retinal photography by an ROP
      specialist. Every infant received outpatient binocular indirect ophthalmoscope
      examinations until termination criteria were achieved or until treatment.
      Outcomes were treatment-warranted ROP (TW-ROP, ETROP type 1) and adverse
      anatomical events. RESULTS: Five hundred eleven infants (1,022 eyes) were
      screened. Fifteen infants had TW-ROP and underwent laser photocoagulation. The TW
      ROP cohort had significantly lower birth weight and gestational age (both P <
      .001). No patient progressed to adverse anatomical outcomes and no case of TW-ROP
      was missed. Tele-medicine had 100% sensitivity, 99.8% specificity, 93.8% positive
      predictive value, and 100% negative predictive value for detection of TW-ROP.
      CONCLUSION: Telemedicine demonstrates high diagnostic accuracy for detection of
      TW-ROP and can complement ROP screening.

PMID- 24444470
TI  - The new FDA reality.

PMID- 24444471
TI  - The role of intravascular ultrasound and quantitative angiography in the
      functional assessment of intermediate coronary lesions: correlation with
      fractional flow reserve.
AB  - BACKGROUND: The correlation between fractional flow reserve (FFR) and
      intravascular ultrasound (IVUS) metrics including minimal lumen area (MLA),
      plaque burden and morphology remain a matter of debate. METHODS: Between June
      2008 and May 2013, 132 intermediate stenoses in 109 patients were assessed by
      FFR, IVUS and quantitative angiography. Receiver-operating characteristic (ROC)
      curve analyses were used to identify MLA/lesion length/plaque burden cut-off
      values predictive of FFR <0.80. RESULTS: FFR <0.80 was observed in 39 lesions. In
      the entire cohort, MLA value <2.70mm(2) had 79.5% sensitivity, 76.3% specificity,
      0.822 area under curve (AUC), 58.5% positive predictive value, 89.9% negative
      predictive value and 77.3% accuracy in predicting a positive FFR. In lesions with
      reference diameter vessel (RVD) >=3.0mm, the MLA cut-off value was 2.84mm(2)
      (sensitivity 72.2%, specificity 83.0%, AUC 0.842) whereas in lesions with RVD
      <3.0mm, 2.59mm(2) (sensitivity 90.5%, specificity 69.6%, AUC 0.823). A moderate
      correlation was observed between MLA and FFR (r=0.429, p<0.001). The cut-off
      lesion length predictive of FFR <0.80 was 11.0mm with a weak correlation between
      the two (r=-0.348, p<0.001). Plaque morphology did not significantly affect FFR
      (p=0.485). On multivariable analysis, MLA (OR: 0.15; 95% CI: 0.05-0.40; p<0.001)
      and plaque burden (OR: 1.11; 95% CI: 1.04-1.20; p<0.003) were independent
      predictors of FFR <0.80. CONCLUSION: A modest, yet significant correlation was
      observed between MLA and FFR. The high negative predictive value of large MLAs
      (using afore-mentioned cut-off values) may provide some degree of confidence that
      the lesion in question is not functionally significant.

PMID- 24444473
TI  - Paclitaxel-coated balloon for the treatment of drug-eluting stent restenosis:
      subanalysis results from the Valentines I trial.
AB  - OBJECTIVES: To analyze the effect of paclitaxel-coated balloon (PCB) treatment on
      patients with drug-eluting stent (DES) restenosis. BACKGROUND: In the Valentines
      I trial, treatment of coronary in-stent restenosis was effective and safe with
      the second-generation DIOR(r) PCB. METHODS: Valentines I prospectively enrolled
      250 patients with in-stent restenosis (ISR); 76 patients (30.4%) had restenosis
      of a previous paclitaxel or limus DES. Patients underwent balloon angioplasty
      followed by PCB treatment. Clinical outcomes of patients with paclitaxel-eluting
      DES restenosis (n=34; 41 lesions) and limus-eluting (sirolimus, everolimus and
      zotarolimus) DES restenosis (n=42; 43 lesions) treated with DIOR(r) PCB were
      compared. RESULTS: Baseline characteristics were similar. There were more diffuse
      lesions >20mm treated in paclitaxel- compared to limus-eluting DES restenosis
      (50% vs. 26.8%, p=0.032). Number of PCB used per patient (1.08+/-0.31 overall),
      mean PCB diameter (2.99+/-0.42mm overall), mean PCB length (24.4+/-11.9mm
      overall), and bailout stenting (2.4% vs. 4.7%) were similar (p=NS). At mean
      follow-up of 231+/-43days, major adverse cardiac events was 0% vs. 23.8% in
      paclitaxel- vs. limus-eluting DES restenosis (p=0.002), driven mainly by less
      target vessel revascularization (0% vs. 21.4%, p=0.004). Target lesion
      revascularization was 0% vs. 16.7% for paclitaxel- vs. limus-eluting DES
      restenosis (p=0.015). CONCLUSION: In Valentines I, PCB use was more effective in
      patients with paclitaxel DES restenosis compared to limus DES restenosis,
      achieving better mid-term clinical outcomes. This suggests the efficacy of
      localized paclitaxel delivery to overcome paclitaxel resistance but not limus
      resistance due to different mechanisms of DES failure.

PMID- 24444474
TI  - EKOSTM ultrasound - accelerated catheter - directed thrombolysis for acutely
      occluded femoro-popliteal graft.
AB  - Acute limb ischemia due to bypass thrombotic occlusion may occur in patients with
      poor collateral circulation. It constitutes a medical emergency with increased
      morbidity, mortality and risk for limb amputation. Although the management of
      acute limb ischemia due to native artery occlusion is well studied, the optimal
      approach of acute bypass graft failure resulting in acute limb ischemia is
      uncertain. We present a case of acute limb ischemia in a patient with femoro
      femoral and femoro-popliteal graft who presented with acute limb ischemia due to
      acute thrombotic occlusion of his femoro-popliteal graft. The patient was
      successfully managed with ultrasound-enhanced catheter-directed thrombolysis
      using the EkoSonic(r) endovascular system with excellent clinical and
      angiographic results. To our knowledge this is the first published report of the
      use of the EkoSonic(r) system for this indication. 

PMID- 24444472
TI  - Correlates for mortality in patients presented with acute myocardial infarct
      complicated by cardiogenic shock.
AB  - OBJECTIVE: This study aimed to explore the correlates for mortality in patients
      treated with both primary percutaneous coronary intervention (PCI) and intra
      aortic balloon pump counter-pulsation (IABP). BACKGROUND: Acute myocardial
      infarction (AMI) complicated by cardiogenic shock (CS) is associated with high
      mortality rates. METHODS: From a cohort of patients with AMI, treated with both
      primary PCI and IABP and who met strict definitions for CS to identify correlates
      associated with mortality, the study compared patients who died in-hospital to
      those who survived to discharge. RESULTS: A cohort of 93 patients met the
      inclusion/exclusion criteria. Of them, 66.7% were male, and the average age was
      64.96+/-13.06years. The overall in-hospital mortality rate for this cohort was
      33%. The baseline characteristics were balanced save for older average age and
      left ventricular ejection fraction in those who died (p=0.049 and p=0.014,
      respectively). Insertion of IABP pre-PCI and cardiac arrest at the
      catheterization lab were more frequent in those who died (p=0.027 and p=0.008,
      respectively). The insertion of IABP pre-PCI, cardiac arrest at the cath lab, and
      lower ejection fraction were correlated with in-hospital mortality (ORs 2.68,
      5.93, and 0.02, respectively). CONCLUSIONS: In the era of primary PCI and IABP as
      standard of care in AMI complicated by CS, patients with low EF, those who
      necessitate IABP insertion pre-PCI, and those who necessitate cardiopulmonary
      resuscitation during PCI are at higher risk for in-hospital mortality and should
      be considered for more robust hemodynamic support devices with an attempt to
      improve their prognosis.

PMID- 24444475
TI  - Synthesis and cytotoxic activity of MOM-ether analogs of isosteviol.
AB  - Lung cancer is one of the most common malignancies worldwide. In this Letter,
      novel MOM-ether analogs of isosteviol were designed and synthesized to be tested
      for anticancer activities against H1299 lung cancer cell lines. The effects of
      these derivatives were studied in H1299 human large cell lung carcinoma cells
      that are null for p53 and compared to normal counterparts NL-20 normal lung
      epithelial cells. The initial screening of twelve MOM-ether analogs of isosteviol
      derivatives on H1299 lung cancer cells by MTT assay revealed that two derivatives
      (an ester and a carbamate) were the most potent in reducing cell viability. The
      IC50 values for these derivatives were determined to be 14 and 21 MUM
      respectively. We compared the cytotoxicity of the best derivatives in H1299 lung
      cancer cells and NL-20 normal lung epithelial cells. Both derivatives showed
      lower cytotoxic effects on NL-20 normal lung epithelial cells. Moreover, both
      derivatives induced apoptosis in H1299 lung cancer cells more than NL-20 normal
      lung epithelial cells.

PMID- 24444476
TI  - Focal therapy in prostate cancer: international multidisciplinary consensus on
      trial design.
AB  - BACKGROUND: Focal therapy has been introduced for the treatment of localised
      prostate cancer (PCa). To provide the necessary data for consistent assessment,
      all focal therapy trials should be performed according to uniform, systematic pre
      and post-treatment evaluation with well-defined end points and strict inclusion
      and exclusion criteria. OBJECTIVE: To obtain consensus on trial design for focal
      therapy in PCa. DESIGN, SETTING, AND PARTICIPANTS: A four-staged consensus
      project based on a modified Delphi process was conducted in which 48 experts in
      focal therapy of PCa participated. According to this formal consensus-building
      method, participants were asked to fill out an iterative sequence of
      questionnaires to collect data on trial design. Subsequently, a consensus meeting
      was held in which 13 panellists discussed acquired data, clarified the results,
      and defined the conclusions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A
      multidisciplinary board from oncologic centres worldwide reached consensus on
      patient selection, pretreatment assessment, evaluation of outcome, and follow-up.
      RESULTS AND LIMITATIONS: Inclusion criteria for candidates in focal therapy
      trials are patients with prostate-specific antigen <15 ng/ml, clinical stage T1c
      T2a, Gleason score 3+3 or 3+4, life expectancy of >10 yr, and any prostate
      volume. The optimal biopsy strategy includes transrectal ultrasound-guided
      biopsies to be taken between 6 mo and 12 mo after treatment. The primary
      objective should be focal ablation of clinically significant disease with
      negative biopsies at 12 mo after treatment as the primary end point. CONCLUSIONS:
      This consensus report provides a standard for designing a feasible focal therapy
      trial. PATIENT SUMMARY: A variety of ablative technologies have been introduced
      and applied in a focal manner for the treatment of prostate cancer (PCa). In this
      consensus report, an international panel of experts in the field of PCa
      determined pre- and post-treatment work-up for focal therapy research.

PMID- 24444477
TI  - A case report of acute right coronary artery thrombosis in young male: the role
      of heredity and genetic polymorphism.

PMID- 24444478
TI  - Revised clinical diagnostic criteria for Tako-tsubo syndrome: the Tako-tsubo
      Italian Network proposal.

PMID- 24444479
TI  - Low socioeconomic status increases short-term mortality of acute myocardial
      infarction despite universal health coverage.
AB  - BACKGROUND: This nationwide population-based study investigated the relationship
      between individual and neighborhood socioeconomic status (SES) and mortality
      rates for acute myocardial infarction (AMI) in Taiwan. METHODS: A population
      based follow-up study included 23,568 patients diagnosed with AMI from 2004 to
      2008. Each patient was monitored for 2 years, or until their death, whichever
      came first. The individual income-related insurance payment amount was used as a
      proxy measure of patient's individual SES. Neighborhood SES was defined by
      household income, and neighborhoods were grouped as advantaged or disadvantaged.
      The Cox proportional hazards model was used to compare the mortality rates
      between the different SES groups after adjusting for possible confounding risk
      factors. RESULTS: After adjusting for potential confounding factors, AMI patients
      with low individual SES had an increased risk of death than those with high
      individual SES who resided in advantaged neighborhoods. In contrast, the
      cumulative readmission rate from major adverse cardiovascular events did not
      differ significantly between the different individual and neighborhood SES
      groups. AMI patients with low individual SES had a lower rate of diagnostic
      angiography and subsequent percutaneous coronary intervention (P<0.001). The
      presence of congestive heart failure, chronic kidney disease, chronic obstructive
      pulmonary disease, pneumonia, septicemia, and shock revealed an incremental
      increase with worse SES (P<0.001). CONCLUSIONS: The findings indicate that AMI
      patients with low individual SES have the greatest risk of short-term mortality
      despite being under a universal health-care system. Public health strategies and
      welfare policies must continue to focus on this vulnerable group.

PMID- 24444480
TI  - Association of Left Superior Vena Cava, Sinus Venosus Defect and partial
      anomalous pulmonary venous return: an echographic and MDCT study.

PMID- 24444481
TI  - To the left-to the right: sustained ventricular bigeminy from the "right"
      ventricular outflow tract in a patient with dextrocardia.

PMID- 24444482
TI  - Minimizing false activation of cath lab for STEMI--a realistic goal?

PMID- 24444483
TI  - The detection rates of inter-arm systolic blood pressure difference vary with
      blood pressure levels in hypertensive patients under antihypertensive therapy.

PMID- 24444484
TI  - Reply to letter to the editor: "adenosine di-phosphate receptor antagonist
      discontinuation management prior to coronary artery surgery".

PMID- 24444485
TI  - Prevalence of patent foramen ovale in atrial fibrillation patients with history
      of cerebral ischemia: a stand-alone additional risk?

PMID- 24444487
TI  - Use of novel biomarkers in heart failure: how and why?

PMID- 24444486
TI  - Contrast volume reduction adapted to body mass index for 320-slice coronary
      computed tomography angiography: results from four-year clinical routine at a
      single center.

PMID- 24444488
TI  - Prescribing warfarin at discharge for heart failure patients: findings from the
      Get With The Guidelines-Heart Failure Registry.

PMID- 24444489
TI  - Various aspects of ultrasound assisted emulsion polymerization process.
AB  - In this paper, the effects of ultrasonic (US) power, pulse ratio, probe area and
      recipe composition were investigated on two process responses namely, monomer
      (methyl methacrylate, MMA) conversion and electrical energy consumption per mass
      of product polymer (PMMA). Pulsed mode US is more suitable than continuous mode
      US for emulsion polymerization. The probe (tip) area has little effect on the
      yield of polymerization when comparing 19 and 13 mm probes, 13 mm probe
      performing slightly better for high conversion levels. Meanwhile, large probe
      area is beneficial for high conversion efficiency of electric energy to US energy
      as well as for high radical generation yield per energy consumed. The conversion
      increased slightly and electrical energy consumption decreased substantially by
      using a recipe with high SDS and monomer concentrations. Conclusions presented in
      this paper may be useful for scale-up of US assisted emulsion polymerization.

PMID- 24444490
TI  - Sonochemical characterisation of ultrasonic dental descalers.
AB  - An ultrasonic dental descaling instrument has been characterised using
      sonochemical techniques. Mapping the emission from luminol solution revealed the
      distribution of cavitation produced in water around the tips. Hydroxyl radical
      production rates arising from water sonolysis were measured using terephthalate
      dosimetry and found to be in the range of MUmolmin(-1), comparable with those
      from a sonochemical horn. Removal of an ink coating from a glass slide showed
      that cleaning occurred primarily where the tip contacted the surface but was also
      observed in regions where cavitation occurred even when the tip did not contact
      the surface. Differences in behaviour were noted between different tip designs
      and computer simulation of the acoustic pressure distributions using COMSOL
      showed the reasons behind the different behaviour of the tip designs. 

PMID- 24444491
TI  - [Organizational recommendations for day surgery].
AB  - In France, the delayed development of day surgery compared to other countries led
      the ANAP and the HAS in 2011 to enter into a joint work program to provide some
      reference guide for hospitals to change their practices to outpatient. In this
      context, organizational guidelines and operational tools were published in May
      2013. The method of construction of the recommendations resulting from an
      original work that combined a three-fold approach: field vision by identifying
      the highlights of 15 hospitals selected for their representative performance and
      analyzing the risks of five voluntary hospitals, mobilization organizational
      theories from the social sciences, using 53 professional experts. The work
      concluded on 16 organizational recommendations under four forms (basic
      principles, strategic elements, operational elements and perspectives). These
      recommendations are accompanied by tools and guides diagnosis and implementation,
      as well as productions for further reflection. These organizational
      recommendations confirmed the specificity of day surgery, which is not related to
      the act, but to the organization, management and optimization of different flows
      of a hospital (patient flow, professional flows, logistical, informational...).
      The performance of a day surgery organization is linked to its ability to control
      its flow and anticipation. 

PMID- 24444492
TI  - Identification of novel loci for bipolar I disorder in a multi-stage genome-wide
      association study.
AB  - OBJECTIVE: Identification of genetic variants that influence bipolar I disorder
      (BPD-I) through genome-wide association (GWA) studies is limited in Asian
      populations. The current study aimed to identify novel common variants for BPD-I
      in an ethnically homogeneous Taiwanese sample using a multi-stage GWA study
      design. METHOD: At the discovery stage, 200 BPD-I patients and 200 controls that
      combined to form 16 pools were genotyped with 1 million markers. Utilizing a
      newly developed rank-based method, top-ranked markers were selected. After
      validation with individual genotyping, a fine-mapping association study was
      conducted to identify associated loci using 240 patients and 240 controls. At the
      last stage, independent samples were collected (351 cases and 341 controls) for
      replication. RESULTS: Among the top-ranked markers from the discovery stage,
      eight genes and 15 individual SNPs were evaluated in the fine-mapping stage. At
      this stage, rs7619173, which is not in a gene coding region, showed the most
      significant association (P = 2 * 10(-5)) with BPD-I. Four genes had empirical P
      values<0.05, including KCNH7 (P = 0.0047), MYST4 (P = 0.0047), NRXN3 (P =
      0.0095), and SEMA3D (P = 0.037). For markers genotyped in replication samples,
      rs7619173 exhibited a significant association (P(combined) = 2 * 10(-4)) after
      multiple testing correction, while markers rs11001178 (MYST4) and rs2217887
      (NRXN3) showed weak associations (P(combined) = 0.02) with BPD-I. CONCLUSION: A
      multi-stage GWA design has the potential to uncover the underlying pathogenesis
      of a complex trait. Findings in the present study highlight three loci that
      warrant further investigation for bipolar.

PMID- 24444493
TI  - Transduced protein transduction domain linked HSP27 protected LECs against UVB
      radiation-induced damage.
AB  - PTD-fusion protein technology was used to transduce heat shock protein 27
      (HSP27), an anti-apoptotic protein, into human lens epithelial cells (HLECs)
      (SRA01/04). The protein transduction domain (PTD) of the 11-amino acid
      YGRKKRRQRRR was tagged at the N-terminus of HSP27. The fusion protein was
      purified from bacteria transformed with a pKYB-PTD-HSP27 construct. The HLECs
      were incubated with PTD-HSP27-FITC and the fluorescence inside HLECs was found by
      fluorescence microscopic examination. To test the ability of PTD-HSP27 to pass
      through the corneas, PTD-HSP27-FITC was dropped onto the conjunctival sacs of
      rabbits; fluorescent labeled PTD-HSP27 was then observed in the rabbit aqueous
      humor. After being incubated with the PTD-HSP27 protein and irradiated with
      ultraviolet-B (UVB) light, HLECs was analyzed by flow cytometry, Hoechst 33258
      staining and measurement of the potential of the mitochondrial transmembrane.
      HLECs incubated with PTD-HSP27 had a lower apoptotic rate and a higher
      mitochondrial membrane potential than the control cells. PTD-HSP27 appears to be
      sufficient to protect HLECs against UVB-induced apoptosis. 

PMID- 24444494
TI  - Nanotechnology in reproductive medicine: emerging applications of nanomaterials.
AB  - In the last decade, nanotechnology has been extensively introduced for biomedical
      applications, including bio-detection, drug delivery and diagnostic imaging,
      particularly in the field of cancer diagnostics and treatment. However, there is
      a growing trend towards the expansion of nanobiotechnological tools in a number
      of non-cancer applications. In this review, we discuss the emerging uses of
      nanotechnology in reproductive medicine and reproductive biology. For the first
      time, we summarise the available evidence regarding the use of nanomaterials as
      experimental tools for the detection and treatment of malignant and benign
      reproductive conditions. We also present an overview of potential applications
      for nanomaterials in reproductive biology, discuss the benefits and concerns
      associated with their use in a highly delicate system of reproductive tissues and
      gametes, and address the feasibility of this innovative and potentially
      controversial approach in the clinical setting and for investigative research
      into the mechanisms underlying reproductive diseases. FROM THE CLINICAL EDITOR:
      This unique review paper focuses on the emerging use of nanotechnology in
      reproductive medicine and reproductive biology, highlighting the role of
      nanomaterials in the detection and treatment of various reproductive conditions,
      keeping in mind the benefits and potential concerns associated with nanomaterial
      use in the delicate system of reproductive tissue and gametes.

PMID- 24444495
TI  - Igloo-Plot: a tool for visualization of multidimensional datasets.
AB  - Advances in science and technology have resulted in an exponential growth of
      multivariate (or multi-dimensional) datasets which are being generated from
      various research areas especially in the domain of biological sciences.
      Visualization and analysis of such data (with the objective of uncovering the
      hidden patterns therein) is an important and challenging task. We present a tool,
      called Igloo-Plot, for efficient visualization of multidimensional datasets. The
      tool addresses some of the key limitations of contemporary multivariate
      visualization and analysis tools. The visualization layout, not only facilitates
      an easy identification of clusters of data-points having similar feature
      compositions, but also the 'marker features' specific to each of these clusters.
      The applicability of the various functionalities implemented herein is
      demonstrated using several well studied multi-dimensional datasets. Igloo-Plot is
      expected to be a valuable resource for researchers working in multivariate data
      mining studies. Igloo-Plot is available for download from:
      http://metagenomics.atc.tcs.com/IglooPlot/. 

PMID- 24444496
TI  - Effects of TSH on the function of human umbilical vein endothelial cells.
AB  - Recent studies have reported that subclinical hypothyroidism (SCH) is associated
      with atherosclerosis (AS). Thyroid hormone is maintained at normal levels in
      patients with SCH, whereas TSH is increased. However, the pathogenesis of AS in
      association with SCH is only partially understood. In addition, endothelial
      dysfunction plays an important role in the development of AS. The purpose of the
      present research was to study the direct effect of TSH on human umbilical vein
      endothelial cells (HUVECs). The expression of some genes associated with
      endothelial dysfunction after treatment with TSH was evaluated by real-time PCR
      and western blotting respectively. At first, we showed that the TSH receptor
      (TSHR) is expressed in HUVECs. We also provide evidence indicating that TSH
      treatment promotes tumor necrosis factor alpha-induced endothelial cells
      interactions by upregulating the expression of the adhesion molecules
      intercellular adhesion molecule-1. Furthermore, the expression of endothelial
      nitric oxide synthase (eNOS) and prostacyclin (PGI2) was significantly attenuated
      following treatment with TSH in dose- and time-dependent manner. Conversely, the
      results indicated that TSH upregulated endothelin-1 (ET1) mRNA and protein
      expression in HUVECs, similar effects were observed for plasminogen activator
      inhibitor-1 (PAI1) after treatment with various concentrations of TSH. Taken
      together, these results demonstrate that elevated TSH can promote endothelial
      dysfunction by altering gene expression in HUVECs.

PMID- 24444497
TI  - A novel 11beta-HSD1 inhibitor improves diabesity and osteoblast differentiation.
AB  - Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      have considerable potential as treatment for osteoporosis as well as metabolic
      syndrome including type 2 diabetes mellitus. Here, we investigated the anti
      diabetic, anti-adipogenic, and anti-osteoporotic activity of KR-67500, as a novel
      selective 11beta-HSD1 inhibitor. Cellular 11beta-HSD1 activity was tested based
      on a homogeneous time-resolved fluorescence method. Oral glucose tolerance test
      (OGTT) and insulin tolerance test (ITT) levels were measured in diet-induced
      obese (DIO)-C57BL/6 mice administered KR-67500 (50  mg/kg per day, p.o.) for 28
      days and, additionally, its anti-diabetic effect was evaluated by OGTT and ITT.
      The in vitro anti-adipogenic effect of KR-67500 was determined by Oil Red O
      Staining. The in vitro anti-osteoporotic activity of KR-67500 was evaluated using
      bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation and
      receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast
      differentiation model systems. KR-67500 improved the in vivo glucose tolerance
      and insulin sensitivity in DIO-C57BL/6 mice. KR-67500 suppressed cortisone
      induced differentiation of 3T3-L1 cells into adipocytes. KR-67500 enhanced BMP2
      induced osteoblastogenesis in C2C12 cells and inhibited RANKL-induced
      osteoclastogenesis in mouse bone marrow-derived macrophages. KR-67500, a new
      selective 11beta-HSD1 inhibitor, may provide a new therapeutic window in the
      prevention and/or treatment of type 2 diabetes, obesity, and/or osteoporosis.

PMID- 24444498
TI  - Revolving scanning transmission electron microscopy: correcting sample drift
      distortion without prior knowledge.
AB  - We report the development of revolving scanning transmission electron microscopy-
      RevSTEM--a technique that enables characterization and removal of sample drift
      distortion from atomic resolution images without the need for a priori crystal
      structure information. To measure and correct the distortion, we acquire an image
      series while rotating the scan coordinate system between successive frames.
      Through theory and experiment, we show that the revolving image series captures
      the information necessary to analyze sample drift rate and direction. At atomic
      resolution, we quantify the image distortion using the projective standard
      deviation, a rapid, real-space method to directly measure lattice vector angles.
      By fitting these angles to a physical model, we show that the refined drift
      parameters provide the input needed to correct distortion across the series. We
      demonstrate that RevSTEM simultaneously removes the need for a priori structure
      information to correct distortion, leads to a dramatically improved signal-to
      noise ratio, and enables picometer precision and accuracy regardless of drift
      rate.

PMID- 24444499
TI  - Staying on track when prescribing off-label.

PMID- 24444500
TI  - Multiple bullae on the trunk.

PMID- 24444502
TI  - Corticosteroids for the treatment of sore throat.

PMID- 24444503
TI  - The role of breathing exercises in the treatment of COPD.

PMID- 24444504
TI  - Evaluation and management of the acutely injured worker.
AB  - Approximately 3 million work-related injuries were reported by private industries
      in 2011, and primary care physicians provided care for approximately one out of
      four injured workers. To appropriately individualize the treatment of an injured
      worker and expedite the return to work process, primary care physicians need to
      be familiar with the workers' compensation system and treatment guidelines.
      Caring for an injured worker begins with a medical history documenting
      preexisting medical conditions, use of potentially impairing medications and
      substances, baseline functional status, and psychosocial factors. An
      understanding of past and current work tasks is critical and can be obtained
      through patient-completed forms, job analyses, and the patient's employer. Return
      to work in some capacity is an important part of the recovery process. It should
      not be unnecessarily delayed and should be an expected outcome communicated to
      the patient during the initial visit. Certain medications, such as opioids, may
      delay the return to work process, and their use should be carefully considered.
      Accurate and legible documentation is critical and should always include the
      location, date, time, and mechanism of injury. 

PMID- 24444505
TI  - Evaluation of the patient with hip pain.
AB  - Hip pain is a common and disabling condition that affects patients of all ages.
      The differential diagnosis of hip pain is broad, presenting a diagnostic
      challenge. Patients often express that their hip pain is localized to one of
      three anatomic regions: the anterior hip and groin, the posterior hip and
      buttock, or the lateral hip. Anterior hip and groin pain is commonly associated
      with intra-articular pathology, such as osteoarthritis and hip labral tears.
      Posterior hip pain is associated with piriformis syndrome, sacroiliac joint
      dysfunction, lumbar radiculopathy, and less commonly ischiofemoral impingement
      and vascular claudication. Lateral hip pain occurs with greater trochanteric pain
      syndrome. Clinical examination tests, although helpful, are not highly sensitive
      or specific for most diagnoses; however, a rational approach to the hip
      examination can be used. Radiography should be performed if acute fracture,
      dislocations, or stress fractures are suspected. Initial plain radiography of the
      hip should include an anteroposterior view of the pelvis and frog-leg lateral
      view of the symptomatic hip. Magnetic resonance imaging should be performed if
      the history and plain radiograph results are not diagnostic. Magnetic resonance
      imaging is valuable for the detection of occult traumatic fractures, stress
      fractures, and osteonecrosis of the femoral head. Magnetic resonance arthrography
      is the diagnostic test of choice for labral tears. 

PMID- 24444506
TI  - Noonan syndrome.
AB  - Noonan syndrome is a common genetic disorder that causes multiple congenital
      abnormalities and a large number of potential health conditions. Most affected
      individuals have characteristic facial features that evolve with age; a broad,
      webbed neck; increased bleeding tendency; and a high incidence of congenital
      heart disease, failure to thrive, short stature, feeding difficulties, sternal
      deformity, renal malformation, pubertal delay, cryptorchidism, developmental or
      behavioral problems, vision problems, hearing loss, and lymphedema. Familial
      recurrence is consistent with an autosomal dominant mode of inheritance, but most
      cases are due to de novo mutations. Diagnosis can be made on the basis of
      clinical features, but may be missed in mildly affected patients. Molecular
      genetic testing can confirm diagnosis in 70% of cases and has important
      implications for genetic counseling and management. Most patients with Noonan
      syndrome are intellectually normal as adults, but some may require
      multidisciplinary evaluation and regular follow-up care. Age-based Noonan
      syndrome-specific growth charts and treatment guidelines are available. 

PMID- 24444507
TI  - Inheriting patients with questionable medication regimens.

PMID- 24444510
TI  - Information from your family doctor. What you should know about hip pain.

PMID- 24444511
TI  - Information from your family doctor. Noonan syndrome: what you should know.

PMID- 24444512
TI  - Understanding the translation of scientific knowledge about arsenic risk exposure
      among private well water users in Nova Scotia.
AB  - Arsenic is a class I human carcinogen that has been identified as the second most
      important global health concern in groundwater supplies after contamination by
      pathogenic organisms. Hydrogeological assessments have shown naturally occurring
      arsenic to be widespread in groundwater across the northeastern United States and
      eastern Canada. Knowledge of arsenic risk exposure among private well users in
      these arsenic endemic areas has not yet been fully explored but research on water
      quality perceptions indicates a consistent misalignment between public and
      scientific assessments of environmental risk. This paper evaluates knowledge of
      arsenic risk exposure among a demographic cross-section of well users residing in
      5 areas of Nova Scotia assessed to be at variable risk (high-low) of arsenic
      occurrence in groundwater based on water sample analysis. An integrated knowledge
      to-action (KTA) methodological approach is utilized to comprehensively assess the
      personal, social and local factors shaping perception of well water contaminant
      risks and the translation of knowledge into routine water testing behaviors.
      Analysis of well user survey data (n=420) reveals a high level of confidence in
      well water quality that is unrelated to the relative risk of arsenic exposure or
      homeowner adherence to government testing recommendations. Further analysis from
      the survey and in-depth well user interviews (n=32) finds that well users'
      assessments of risk are influenced by personal experience, local knowledge,
      social networks and convenience of infrastructure rather than by formal
      information channels, which are largely failing to reach their target audiences.
      Insights from interviews with stakeholders representing government health and
      environment agencies (n=15) are used to reflect on the institutional barriers
      that mediate the translation of scientific knowledge into public awareness and
      stewardship behaviors. The utilization of local knowledge brokers, community
      based networks and regulatory incentives to improve risk knowledge and support
      routine testing among private well users is discussed. 

PMID- 24444513
TI  - Polybrominated diphenyl ether concentrations in sediments from the Northern
      Arabian Gulf: spatial and temporal trends.
AB  - Surficial sediment samples were obtained from 25 locations within Kuwait Bay and
      outside the Bay, in the Northwestern Arabian Gulf, to access recent pollution in
      Kuwait. The historical deposition of PBDEs to this portion of the Arabian Gulf
      was reconstructed by collecting a sediment core at the entrance of Kuwait Bay.
      The mean (and range) in concentrations of ?11PBDEs in surficial sediments was
      0.164+/-0.09 (0.06-0.44) pg/g dw. The concentrations measured in Kuwait Bay were
      generally higher than those measured in the open Gulf. When the concentrations
      were normalized to organic carbon, the average ?11PBDEs concentrations measured
      in Kuwait Bay were seven times higher than average concentrations outside the
      Bay. The historical record, reconstructed from a sediment core collected at the
      entrance of Kuwait Bay, showed that Sigma11PBDE concentrations were generally low
      in deeper sediment sections. The concentrations started to increase above
      background in the mid-1950s and increased sharply to a maximum Sigma11PBDE
      concentration of ca 1,100 pg/g in the late 1980s. Concentrations decreased
      thereafter until another pulse in concentrations was observed around the early
      2000 followed by a decrease in subsequent years. It is likely that the initial
      pulse in concentration recorded in sediments is related to inputs from the Gulf
      war of 1991. The penta congeners were observed throughout the length of the core
      although the concentrations were low. The congeners present in the Deca-PBDE
      technical mixture, particularly BDE 209 which is the main congener in the Deca
      BDE mixture, occurred in sediment cores around the 1980s, and the concentrations
      increased rapidly thereafter being the most dominant congener since their first
      detection in sediments. The presence of nona-BDE congeners in proportions
      exceeding those in commercial mixtures may be suggestive of debromination of BDE
      209 in sediments.

PMID- 24444514
TI  - Atomic scale simulations of pyrochlore oxides with a tight-binding variable
      charge model: implications for radiation tolerance.
AB  - Atomistic simulations with new interatomic potentials derived from a tight
      binding variable-charge model were performed in order to investigate the lattice
      properties and the defect formation energies in Gd2Ti2O7 and Gd2Zr2O7
      pyrochlores. The main objective was to determine the role played by the defect
      stability on the radiation tolerance of these compounds. Calculations show that
      the titanate has a more covalent character than the zirconate. Moreover, the
      properties of oxygen Frenkel pairs, cation antisite defects and cation Frenkel
      pairs were studied. In Gd2Ti2O7 the cation antisite defect and the Ti-Frenkel
      pair are not stable: they evolve towards more stable defect configurations during
      the atomic relaxation process. This phenomenon is driven by a decrease of the Ti
      coordination number down to five which leads to a local atomic reorganization and
      strong structural distortions around the defects. These kinds of atomic
      rearrangements are not observed around defects in Gd2Zr2O7. Therefore, the defect
      stability in A2B2O7 depends on the ability of B atoms to accommodate high
      coordination number (higher than six seems impossible for Ti). The accumulation
      of structural distortions around Ti-defects due to this phenomenon could drive
      the Gd2Ti2O7 amorphization induced by irradiation. 

PMID- 24444515
TI  - Improving students' long-term knowledge retention through personalized review.
AB  - Human memory is imperfect; thus, periodic review is required for the long-term
      preservation of knowledge and skills. However, students at every educational
      level are challenged by an ever-growing amount of material to review and an
      ongoing imperative to master new material. We developed a method for efficient,
      systematic, personalized review that combines statistical techniques for
      inferring individual differences with a psychological theory of memory. The
      method was integrated into a semester-long middle-school foreign-language course
      via retrieval-practice software. Using a cumulative exam administered after the
      semester's end, we compared time-matched review strategies and found that
      personalized review yielded a 16.5% boost in course retention over current
      educational practice (massed study) and a 10.0% improvement over a one-size-fits
      all strategy for spaced study. 

PMID- 24444516
TI  - [Introduction].

PMID- 24444517
TI  - [Control of type 2 diabetes mellitus in Spain today: identification of the main
      obstacles in daily clinical practice].
AB  - Type 2 diabetes mellitus (DM2) is a highly prevalent chronic disease with major
      social and healthcare repercussions due to the development of acute and chronic
      complications. The care of patients with DM2 represents between 6.3% and 7.4% of
      the budget of the Spanish national health service and is mainly centered on
      hospital admissions and hypoglycemic agents, leading to an annual expenditure of
      1.290 ? to 1.476 ? per patient. The attainment of glycemic targets remains
      complex and inadequate, despite new drugs for the treatment of DM2, the available
      scientific evidence, and national and international guidelines. The main causes
      proposed for failure to achieve these targets in DM2 are clinical inertia (found
      in 40% of physicians in Spain treating patients with HbA1c > 7%), poor treatment
      adherence, the problems inherent to the health system, and the natural history of
      the disease. 

PMID- 24444518
TI  - [Type 2 diabetes mellitus and cardiovascular risk factors: is comprehensive
      treatment required?].
AB  - Diabetes mellitus, especially type 2, is a metabolic disease involving the
      coexistence of several cardiovascular risk factors. Affected patients are
      therefore at high cardiovascular risk (2-3 times higher than that of men in the
      general population and 2-6 times higher than that of women). Cardiovascular
      disease is the main cause of death in the diabetic population, followed by
      cancer. Cardiovascular risk cannot be compared between diabetic patients and
      persons who have already shown one or more manifestations of cardiovascular
      disease (such as myocardial infarction). Single risk factors should be evaluated
      in combination with other risk factors and a person's cardiovascular risk should
      be individually assessed. Cardiovascular risk assessment in patients with
      diabetes through current calculations methods is complex because their ability to
      predict risk in individuals is very low. Studies such as that by Steno have
      demonstrated the validity of a comprehensive strategy to control all the risk
      factors present in persons with type 2 diabetes mellitus, which can reduce the
      development of micro- and macrovascular complications and mortality by almost
      50%. The present article reviews each of the classical cardiovascular risk
      factors (hypertension, dyslipidemia, smoking, obesity, sedentariness) in relation
      to diabetes, as well as their recommended targets and the benefits of their
      control. In view of the above, a comprehensive approach is recommended to control
      the multiple risk factors that can coexist in persons with type 2 diabetes
      mellitus.

PMID- 24444519
TI  - [Type 2 diabetes mellitus and obesity: should we treat the obesity or the
      diabetes?].
AB  - In this article, we review the results that can be expected after significant
      weight loss in patients with type 2 diabetes mellitus. We provide consensus-based
      documentation supported by the American Diabetes Association, the European
      Association for the Study of Diabetes, and the International Diabetes Federation
      on the importance of physical exercise, metabolic-bariatric surgery, and drug
      therapy. Lastly, we report the results of studies published in the last few years
      on glucagon-like peptide-1 analogs and the new family of oral drugs known as
      gliflozins, specifically studies published on dapagliflozin. 

PMID- 24444520
TI  - [Limitations of insulin-dependent drugs in the treatment of type 2 diabetes
      mellitus].
AB  - In this study, we review the efficacy and safety limitations of insulin-dependent
      oral antidiabetic agents. In terms of efficiency, the main drawback of metformin,
      sulfonylureas, gliptins and -to a lesser extent-glitazones is durability. No drug
      per se is able to maintain stable blood glucose control for years. Metformin,
      sulfonylureas and gliptins have demonstrated safety. Experience with the first
      two drug groups is more extensive. The main adverse effect of metformin is
      gastrointestinal discomfort. Major concerns related to the use of sulfonylureas
      are hypoglycemia and weight gain. The use of pioglitazone has been associated
      with an increased risk of bladder cancer, edema, heart failure, weight gain, and
      distal bone fractures in postmenopausal women. The most common adverse reactions
      associated with glucagon-like peptide-1 agonists are gastrointestinal discomfort
      that sometimes leads to treatment discontinuation. 

PMID- 24444521
TI  - [Contribution of the kidney to glucose homeostasis].
AB  - The kidney is involved in glucose homeostasis through three major mechanisms:
      renal gluconeogenesis, renal glucose consumption, and glucose reabsorption in the
      proximal tubule. Glucose reabsorption is one of the most important physiological
      functions of the kidney, allowing full recovery of filtered glucose, elimination
      of glucose from the urine, and prevention of calorie loss. Approximately 90% of
      the glucose is reabsorbed in the S1 segment of the proximal tubule, where glucose
      transporter-2 (GLUT2) and sodium-glucose transporter-2 (SGLT2) are located, while
      the remaining 10% is reabsorbed in the S3 segment by SGLT1 and GLUT1
      transporters. In patients with hyperglycemia, the kidney continues to reabsorb
      glucose, thus maintaining hyperglycemia. Most of the renal glucose reabsorption
      is mediated by SGLT2. Several experimental and clinical studies suggest that
      pharmacological blockade of this transporter might be beneficial in the
      management of hyperglycemia in patients with type 2 diabetes.

PMID- 24444522
TI  - [Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and
      familial renal glycosuria to the treatment of type 2 diabetes mellitus].
AB  - The therapeutic armamentarium for the treatment of hyperglycemia in type 2
      diabetes mellitus is still inadequate. We are currently witnessing the
      introduction of a new mode of hypoglycemic treatment through induction of
      glycosuria to decrease the availability of the metabolic substrate, i.e. glucose.
      Clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2)
      inhibitors are as efficacious as other oral hypoglycemic drugs. This article
      discusses the basic features of this new treatment concept and the efficacy and
      safety of this new drug group. 

PMID- 24444523
TI  - [Dapagliflozin, the first SGLT-2 inhibitor in the treatment of type 2 diabetes].
AB  - Dapagliflozin is the first novel sodium-glucose co-transporter-2 (SGLT2)
      inhibitor approved by the European Medicines Agency (EMA) for the treatment of
      type 2 diabetes. By inhibiting SGLT2, dapagliflozin blocks reabsorption of
      filtered glucose in the kidney, increasing urinary glucose excretion and reducing
      blood glucose levels. Its mechanism of action is independent of pancreatic beta
      cell function and modulation of insulin sensitivity. The results of phase III
      clinical trials showed that dapagliflozin, at a dose of 5 or 10mg/day for 24
      weeks as monotherapy in previously untreated patients, or as add-on combination
      therapy with metformin, glimepiride, pioglitazone or insulin-based therapy,
      significantly reduced both HbA1c and fasting plasma glucose levels compared with
      placebo. In addition, dapagliflozin was noninferior to glipizide, in terms of
      glycemic control after 52 weeks, when used as add-on therapy in patients with
      type 2 diabetes inadequately controlled with metformin. In most clinical trials,
      dapagliflozin reduced body weight. The combination of both effects (improved
      glycemic control and weight loss) is achieved to a greater extent in treatments
      that include dapaglifozin. Longer-term extension studies indicated that the
      efficacy of dapagliflozin on the glycemic control and weight reduccion is
      maintained for up to 2 and 4 years. Dapagliflozin was well tolerated. Genital
      infections and urinary tract infections were more frequent in patients who
      received dapagliflozin than in placebo recipients. Hypoglycemic episodes were
      scarce with dapagliflozin. In conclusion, dapagliflozin is a novel option for the
      management of type 2 diabetes, particularly when used as add-on therapy. 

PMID- 24444524
TI  - Role of endorectal MR imaging and MR spectroscopic imaging in defining treatable
      intraprostatic tumor foci in prostate cancer: quantitative analysis of imaging
      contour compared to whole-mount histopathology.
AB  - PURPOSE: To investigate the role of endorectal MR imaging and MR spectroscopic
      imaging in defining the contour of treatable intraprostatic tumor foci in
      prostate cancer, since targeted therapy requires accurate target volume
      definition. MATERIALS AND METHODS: We retrospectively identified 20 patients with
      prostate cancer who underwent endorectal MR imaging and MR spectroscopic imaging
      prior to radical prostatectomy and subsequent creation of detailed
      histopathological tumor maps from whole-mount step sections. Two experienced
      radiologists independently reviewed all MR images and electronically contoured
      all suspected treatable (>=0.5 cm(3)) tumor foci. Deformable co-registration in
      MATLAB was used to calculate the margin of error between imaging and
      histopathological contours at both capsular and non-capsular surfaces and the
      treatment margin required to ensure at least 95% tumor coverage. RESULTS:
      Histopathology showed 17 treatable tumor foci in 16 patients, of which 8 were
      correctly identified by both readers and an additional 2 were correctly
      identified by reader 2. For all correctly identified lesions, both readers
      accurately identified that tumor contacted the prostatic capsule, with no error
      in contour identification. On the non-capsular border, the median distance
      between the imaging and histopathological contour was 1.4mm (range, 0-12).
      Expanding the contour by 5mm at the non-capsular margin included 95% of tumor
      volume not initially covered within the MR contour. CONCLUSIONS: Endorectal MR
      imaging and MR spectroscopic imaging can be used to accurately contour treatable
      intraprostatic tumor foci; adequate tumor coverage is achieved by expanding the
      treatment contour at the non-capsular margin by 5mm.

PMID- 24444525
TI  - Second cancer risk after 3D-CRT, IMRT and VMAT for breast cancer.
AB  - PURPOSE: Second cancer risk after breast conserving therapy is becoming more
      important due to improved long term survival rates. In this study, we estimate
      the risks for developing a solid second cancer after radiotherapy of breast
      cancer using the concept of organ equivalent dose (OED). MATERIALS AND METHODS:
      Computer-tomography scans of 10 representative breast cancer patients were
      selected for this study. Three-dimensional conformal radiotherapy (3D-CRT),
      tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity
      modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were
      planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose
      volume histograms (dDVHs) were created and the OEDs calculated. Second cancer
      risks of ipsilateral, contralateral lung and contralateral breast cancer were
      estimated using linear, linear-exponential and plateau models for second cancer
      risk. RESULTS: Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t
      IMRT, m-IMRT and VMAT were increased by 2 +/- 15%, 131 +/- 85%, 123 +/- 66% for
      the linear-exponential risk model, 9 +/- 22%, 82 +/- 96%, 71 +/- 82% for the
      linear and 3 +/- 14%, 123 +/- 78%, 113 +/- 61% for the plateau model,
      respectively. CONCLUSION: Second cancer risk after 3D-CRT or t-IMRT is lower than
      for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear
      exponential and plateau models, respectively.

PMID- 24444526
TI  - A phase I study of concurrent chemotherapy and thoracic radiotherapy with oral
      epigallocatechin-3-gallate protection in patients with locally advanced stage III
      non-small-cell lung cancer.
AB  - BACKGROUND AND PURPOSE: Patients with unresectable stage III non-small-cell lung
      cancer receiving concurrent chemoradiotherapy often develop esophagitis that may
      lead to unplanned treatment interruptions, which may severely reduce rates of
      locoregional tumor control and survival. No effectivetreatment that would reduce
      the incidence and severity of this complication has been identified up to now.
      Although acceleration of normal tissue protection using epigallocatechin-3
      gallate (EGCG) has been reported, its actual clinical practicability remains
      obscure. METHODS AND MATERIALS: This is a phase I study of EGCG in combination
      with standard chemoradiation in surgically unresectable stage III non-small-cell
      lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with
      radiation. EGCG solution was swallowed three times a day after the occurrence of
      grade 2 esophagitis at six concentration levels and dose escalation followed a
      standard phase I design. Esophageal toxicity and patient-reported pain was
      recorded weekly. RESULTS: Twenty-four patients with AJCC stage IIIA (six) and
      IIIB (eighteen) completed the course of therapy. Twelve had squamous histology,
      ten adenocarcinoma, and two not specified. Patients were treated in six cohorts
      at six dose levels of EGCG. RT was not interrupted with a median dose of 64 Gy.
      There were no dose-limiting toxicities reported in all EGCG dosing tiers.
      Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24
      patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of
      radiotherapy. The pain score was also reduced from a mean of 4.58 (N=24), 1.29
      (N=24), 1.42 (N=24), 0.96 (N=23) to 1.13 (N=16) every week in turn. CONCLUSION:
      We conclude that the oral administration of EGCG is feasible, safe and effective.
      The phase II recommended concentration is 440 MUmol/L.

PMID- 24444527
TI  - Long-term survival of stage T4N0-1 and single station IIIA-N2 NSCLC patients
      treated with definitive chemo-radiotherapy using individualised isotoxic
      accelerated radiotherapy (INDAR).
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) stage T4N0-1 or single nodal
      station IIIA-N2 are two stage III sub-groups for which the outcome of non
      surgical therapy is not well known. We investigated the results of individualised
      isotoxic accelerated radiotherapy (INDAR) and chemotherapy in this setting.
      METHODS: Analysis of NSCLC patients included in 2 prospective trials (NCT00573040
      and NCT00572325) stage T4N0-1 or IIIA-N2 with 1 pathologic nodal station, treated
      with chemo-radiotherapy (CRT) using INDAR with concurrent or sequential platinum
      based chemotherapy. Overall survival (OS) was updated and calculated from date of
      diagnosis (Kaplan-Meier). Toxicity was scored following CTCAEv3.0. To allow
      comparison with other articles the subgroups were also analysed separately for
      toxicity, progression free and overall survival. RESULTS: 83 patients (42 T4N0-1
      and 41 IIIA-N2) were identified: the median radiotherapy dose was 65Gy. Thirty
      seven percent of patients received sequential CRT and 63% received concurrent
      CRT. At a median follow-up of 48 months the median OS for T4N0-1 patients was 34
      months with 55% 2-year survival and 25% 5-year survival. For stage IIIA-N2 at a
      median follow-up of 50 months the median OS was 26 months with 2- and 5-year
      survival rates of 53% and 24%, respectively. CONCLUSION: Chemo-radiation using
      INDAR yields promising survival results in patients with single-station stage
      IIIA-N2 or T4N0-1 NSCLC.

PMID- 24444528
TI  - Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic
      conditions.
AB  - BACKGROUND AND PURPOSE: Gold nanoparticles (GNPs) are novel agents that have been
      shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is
      associated with radiation resistance and reduced survival in cancer patients. The
      interaction of GNPs with cells in hypoxia is explored. MATERIALS AND METHODS: GNP
      uptake, localization, toxicity and radiosensitisation were assessed in vitro
      under oxic and hypoxic conditions. RESULTS: GNP cellular uptake was significantly
      lower under hypoxic than oxic conditions. A significant reduction in cell
      proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was
      observed. In these cells significant radiosensitisation occurred in normoxia and
      moderate hypoxia. However, in near anoxia no significant sensitisation occurred.
      CONCLUSIONS: GNP uptake occurred in hypoxic conditions, causing
      radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell
      line. These findings may be important for the development of GNPs for cancer
      therapy.

PMID- 24444529
TI  - A clinical nomogram and recursive partitioning analysis to determine the risk of
      regional failure after radiosurgery alone for brain metastases.
AB  - PURPOSE: This investigation defined patient populations at high-, intermediate-,
      and low-risk of regional failure (RF) after stereotactic radiosurgery (SRS)
      lesion treatment using clinical nomograms and recursive partitioning analysis
      (RPA). METHODS AND MATERIALS: We created a retrospective database compiling 361
      oligometastatic brain metastases patients treated with single-modality Linac
      based SRS. Logistic analysis was performed to identify factors to be included in
      a RPA to predict for cumulative RF at 1-year. A 1-year cumulative RF clinical
      nomogram was constructed and validated (c-index statistic). RESULTS: Age, number
      of brain metastases, World Health Organization (WHO) performance status (PS), and
      maximum gross tumor volume (GTV) size were found to be statistically significant
      predictors of the primary outcome. RPA classifications were defined as follows:
      low-risk (<25% 1-year RF): solitary lesion AND age >55Y; intermediate-risk (25
      40% 1-year RF): age ?55Y AND solitary lesion OR WHO?1 AND 2-3 lesions; and high
      risk (>40% 1-year RF): WHO PS=0 AND 2-3 lesions. These classifications were
      highly statistically significant (p<0.01) for RF. A clinical nomogram (containing
      patient age, lesion number, largest GTV volume, and WHO PS) for the prediction of
      1-year cumulative RF was created (c-index 0.69). CONCLUSION: A risk-adapted
      treatment approach can be applied for BM radiosurgery either using RPA categories
      and/or nomogram-based risk estimates.

PMID- 24444530
TI  - Thoracic re-irradiation using stereotactic body radiotherapy (SBRT) techniques as
      first or second course of treatment.
AB  - BACKGROUND AND PURPOSE: Management for in-field failures after thoracic radiation
      is poorly defined. We evaluated SBRT as an initial or second course of treatment
      re-irradiating in a prior high dose region. MATERIALS AND METHODS: Thirty-three
      patients were treated with re-irradiation defined by the prior 30 Gy isodose
      line. Kaplan-Meier estimates were performed for local (LC), regional (RC),
      distant control (DC), and overall survival (OS). The plans when available were
      summed to evaluate doses to critical structures. Patient and treatment variables
      were analyzed on UVA for the impact on control and survival measures. RESULTS:
      Median follow-up was 17 months. Treatment for sequential courses was as follows:
      (course1:course2) EBRT:SBRT (24 patients), SBRT:SBRT (7 patients), and SBRT:EBRT
      (3 patients). Median re-irradiation dose and fractionation was 50 Gy and 10
      fractions (fx), with a median of 18 months (6-61) between treatments. Median OS
      was 21 months and 2 year LC 67%, yet LC for >1 fraction was 88% (p=0.006 for
      single vs. multiple). 10 patients suffered chronic grade 2-3 toxicity (6 chest
      wall pain, 3 dyspnea, 1 esophagitis) and 1 grade 5 toxicity with aorta-esophageal
      fistula after 54 Gy in 3 fx for a central tumor with an estimated EQD2 to the
      aorta of 200 Gy. CONCLUSION: Tumor control can be established with re-irradiation
      using SBRT techniques for in-field thoracic failures at the cost of manageable
      toxicity.

PMID- 24444531
TI  - Treatment adherence in concurrent chemoradiation in patients with locally
      advanced non-small cell lung carcinoma: results of daily intravenous
      prehydration.
AB  - PURPOSE: To test the hypothesis that daily intravenous pre-hydration decreases
      renal toxicity and improves chemotherapy adherence in patients receiving daily
      cisplatin to concurrent radiotherapy for locally advanced non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Patients with locally advanced NSCLC were
      treated between 2008 and August 2012 with daily 6 mg/m(2) cisplatin as a bolus
      injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since
      January 2011, the administration of cisplatin was routinely preceded by
      intravenous pre-hydration with 1L of natriumchloride 0.9%. Patients were divided
      in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and
      glomerular filtration rate (GFR) were assessed twice weekly during treatment.
      Retrospectively, baseline data, toxicity, treatment adherence and efficacy data
      were compared. RESULTS: Of the 356 patients 232 NPH patients and 100 PH patients
      were eligible. Patient-and treatment characteristics compared equally. The median
      of the maximum decrease in GFR was 24% and 8% for NPH and PH (p<0.01),
      respectively. Sixty-nine percent of the patients in the NPH group completed the
      24 administrations of cisplatin, as compared to 83% of the PH group (p<0.01).
      Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued
      cisplatin treatment because of renal toxicity. Surprisingly, the incidence of
      acute esophageal toxicity grade ? 2 decreased following prehydration: 62% vs. 34%
      (p<0.001) for the NPH and PH groups, respectively. The one-year survival was
      comparable between groups (75% for NPH and 71% for PH). CONCLUSION: Daily pre
      hydration was associated with a reduced rate of both renal and acute esophageal
      toxicity and an increased chemotherapy adherence in patients receiving daily dose
      of cisplatin and concurrent radiotherapy for locally advanced NSCLC.

PMID- 24444532
TI  - Attentional resource allocation and swallowing safety in Parkinson's disease: a
      dual task study.
AB  - BACKGROUND: Aspiration pneumonia is a leading cause of death in persons with
      Parkinson's disease (PD). Despite this, the mechanisms underlying dysphagia in
      this population are unclear. To date, researchers have not investigated the
      effects of varying cognitive demand on objective measures of swallowing safety.
      This study assessed whether swallowing safety could be disrupted by increasing
      cognitive demands during the task of swallowing. METHODS: Twenty participants
      with moderate PD and dysphagia were tested while completing a novel dual task
      experimental paradigm under videofluoroscopy. In the dual task condition,
      participants swallowed 10 cc of thin liquid barium while completing a digits
      forward task. RESULTS: Four females and 16 males completed the study. Results
      revealed differential effects to swallowing safety based on baseline measures of
      cognitive flexibility and attention. Participants with mild impairment in
      cognitive flexibility and attention demonstrated cognitive-motor interference
      with worsening of both swallowing and cognitive performance. In contrast,
      participants who were most impaired in the domains of cognitive flexibility and
      attention improved swallowing safety in the dual task condition. Additionally,
      decreased swallow timing durations existed in the dual task condition compared to
      the single task condition. CONCLUSIONS: The results of this study support the
      hypothesis that supramedullary drive can influence the swallowing plan.
      Additionally, this study highlights the need for cognitive taxing during
      swallowing evaluations.

PMID- 24444534
TI  - Inorganic arsenic trioxide induces gap junction loss in association with the
      downregulation of connexin43 and E-cadherin in rat hepatic "stem-like" cells.
AB  - Chronic exposure to inorganic arsenic trioxide causes tumors of the skin, urinary
      bladder, lung, and liver. Several cancer initiators and promoters have been shown
      to alter cell-cell signaling by interference with gap junction intercellular
      communication (GJIC) and/or modulation of cell adhesion molecules, such as
      connexin43 (Cx43), E-cadherin, and beta-catenin. The aim of this study was to
      determine whether the disruption of cell-cell interactions occurs in liver
      epithelial cells after exposure to arsenic trioxide. WB-F344 cells were treated
      with arsenic trioxide (6.25-50 MUM) for up to 8 hours, and gap junction function
      was analyzed using the scrape-load/dye transfer assay. In addition, the changes
      in mRNA and protein levels of Cx43, E-cadherin, and beta-catenin were determined.
      A significant dose- and time-dependent decrease in GJIC was observed when WB-F344
      cells were exposed to arsenic trioxide (p < 0.05). Consistent with the inhibition
      of GJIC, cells' exposure to arsenic trioxide resulted in dose- and time-dependent
      decreases in Cx43 and E-cadherin mRNA expression and protein levels. However,
      arsenic trioxide did not alter the mRNA or protein levels of beta-catenin. In an
      immunofluorescence study, nuclei were heavily stained with anti-beta-catenin
      antibody, indicating significant nuclear translocation. In this study, we also
      demonstrated that arsenic trioxide-induced GJIC loss was a reversible process.
      Taken together, these data support the hypothesis that disruption of cell-cell
      communication may contribute to the tumor-promoting effect of inorganic arsenic
      trioxide. 

PMID- 24444533
TI  - Non-motor phenotype of dopa-responsive dystonia and quality of life assessment.
AB  - BACKGROUND: Dopa-responsive dystonia (DRD) is a young-onset neurometabolic
      disorder often presenting with a combination of parkinsonism and dystonia. The
      pathophysiology includes an impairment of dopaminergic and serotonergic
      neurotransmission. Uncontrolled reports suggest an increased frequency of
      neuropsychiatric abnormalities and sleep impairment. METHODS: In 23 GCH1 mutation
      positive DRD patients and 26 healthy controls, non-motor features and their
      effect on the quality of life (QoL) were assessed. Six patients underwent
      polysomnography (PSG). RESULTS: Depressive and anxiety symptoms were not more
      common among DRD patients. Average sleep quality was similar across groups. This
      was also true for self-reported mean sleep onset (27.5 vs. 27.1 min) and total
      sleep time (6.5 vs. 6.6 h). Upon PSG, the number of spontaneous arousals was
      increased in four patients. QoL was impaired with respect to physical health.
      Sleep impairment and depressive but not anxiety symptoms were associated with
      lower QoL. CONCLUSION: The present results do not confirm the clinical impression
      and biologically plausible assumption of an increased frequency of non-motor
      symptoms in DRD. The impairment of QoL is associated with a decline of the
      physical condition only but not with other factors.

PMID- 24444535
TI  - Remote intrathecal morphine preconditioning is ineffective in the presence of
      neuraxial blockade with lidocaine.
AB  - Remote intrathecal morphine preconditioning (RMPC) induces cardioprotection via a
      neural pathway. Intrathecal lidocaine (LID) blocks spinal cord nerve
      transmission. This study examine whether LID prevents the effects of RMPC.
      Anesthetized, open chest, male Sprague-Dawley rats were assigned to one of seven
      treatment groups 3 days after intrathecal catheter placement. Rats from both RMPC
      and LID groups, respectively, received intrathecal morphine (3 MUg/kg) and
      lidocaine (1%, 10 MUL); morphine was administered by three cycles of 5-minute
      infusions interspersed with 5-minute infusion-free periods. The LID + RMPC group
      received the combination of LID and RMPC. Intrathecal naloxone methiodide (NM)
      (20 MUg/kg) was administered either 15 minutes before RMPC, or 5 minutes before
      LID + RMPC. Ischemia and reperfusion injury were then induced by 30 minutes of
      left coronary artery occlusion, followed by 120 minutes of reperfusion. Infarct
      size, as a percentage of the area at risk (AAR), was determined by 2,3,5
      triphenyltetrazolium staining. The RMPC and LID groups markedly reduced the
      infarct size (IS) compared with controls. LID prevented the effect of RMPC. NM
      had no effect on control and LID + RMPC treatments. However, NM pretreatment
      reversed cardioprotection of RMPC treatment. Intrathecal morphine preconditioning
      is ineffective in the presence of neuraxial blockade with lidocaine. 

PMID- 24444536
TI  - The aqueous extract from Toona sinensis leaves inhibits microglia-mediated
      neuroinflammation.
AB  - The leaves of Toona sinensis, a well-known traditional oriental medicine, have
      been prescribed for the treatment of enteritis and infection. Recently, aqueous
      extracts of Toona sinensis leaves (TSL-1) have demonstrated many biological
      effects both in vitro and in vivo. In the central nervous system, microglial
      activation and their proinflammatory responses are considered an important
      therapeutic strategy for neuroinflammatory disorders such as cerebral ischemia,
      Alzheimer's disease, and Parkinson's disease. The present study attempted to
      validate the effect of TSL-1 on microglia-mediated neuroinflammation stimulated
      by lipopolysaccharide (LPS). As inflammatory parameters, the production of nitric
      oxide (NO), inducible NO synthase, and tumor necrosis factor-alpha were
      evaluated. Our results demonstrate that TSL-1 suppresses LPS-induced NO
      production, tumor necrosis factor-alpha secretion, and inducible NO synthase
      protein expression in a concentration-dependent manner, without causing
      cytotoxicity. In addition, the inhibitory effects of TSL-1 in LPS-stimulated BV-2
      microglia were extended to post-treatment suggesting the therapeutic potential of
      TSL-1. Therefore, this work provides the future evaluation of the role of TSL-1
      in the treatment of neurodegenerative diseases by inhibition of inflammatory
      mediator production in activated microglia. 

PMID- 24444537
TI  - Oral etoposide and oral prednisone for the treatment of castration resistant
      prostate cancer.
AB  - Treatment options for patients with castration-resistant prostate cancer (CRPC)
      are limited. The purpose of our study was to investigate the safety and efficacy
      in terms of prostate-specific antigen (PSA) response of a low-dose oral
      combination of etoposide and prednisone in patients with CRPC. Thirty-nine
      patients with prostate cancer (median age, 77.9 years) with progressive disease
      after standard hormonal therapy were enrolled. Etoposide (25 mg, twice daily) and
      prednisone (5 mg, twice daily) were administered orally. Each cycle comprised 21
      consecutive days of treatment followed by a 7-day drug holiday. All patients
      previously treated with an antiandrogen were required to undergo antiandrogen
      withdrawal prior to entry into the study. A total of 226 cycles were administered
      with a median of 6.7 cycles per patient (range, 1-18 cycles). Sixteen of 39
      patients (41%) with elevated PSA levels at baseline achieved at least a 50%
      reduction in PSA levels. Median progression-free survival for all patients was
      5.9 months (range, 1-17 months). No Grade 4 toxicities were observed. The
      predominant toxicities were mucositis, nausea, fatigue, and anemia in twelve,
      nine, eight, and seven patients, respectively. Hematologic toxicity was
      infrequent, with no episodes of febrile neutropenia. The combination of low-dose
      etoposide and prednisone is an efficacious and reasonably well-tolerated oral
      regimen in the treatment of elderly patients with CRPC. This regimen can be
      easily administered in an outpatient setting and does not require frequent
      patient visits. 

PMID- 24444538
TI  - Maternal diabetes or hypertension and lifestyle factors may be associated with
      metabolic syndrome: a population-based study in Taiwan.
AB  - Early detection and interventions for metabolic syndrome (MetS) are the most cost
      effective methods for preventing many chronic diseases. There have been
      discordant findings in various countries due to different genetics and
      lifestyles. The goal of this study was to investigate the association of MetS
      with parental diseases, a Chinese-style diet, and rural-urban regional
      differences with a large-scale epidemiological survey in Taiwan. Data were
      obtained from the Taiwanese Survey on Hypertension, Hyperglycemia, and
      Hyperlipidemia (TwSHHH), a cross-sectional population-based study with multistage
      stratified random sampling conducted by the Taiwan Bureau of Health Promotion in
      2002. Public health nurses visited homes to conduct the survey, including blood
      drawing and an interview. Multiple logistic regression analysis was used for
      exploring the factors associated with MetS. A total of 6591 people completed data
      for analysis. Our results revealed that older age, male sex, and maternal
      diabetes or hypertension, were significantly associated with MetS. Eating poultry
      with skin and fat and eating a bean-free diet may be associated with a higher
      risk of MetS. People who exercised regularly and the residents of the Taipei
      metropolitan area had a lower prevalence of MetS. As a result, people with
      maternal diabetes or hypertension should pay attention to their cardiovascular
      health and prevention of MetS. We suggest that eating skinless and low-fat
      poultry, eating more beans, and exercising regularly, may decrease the risk of
      MetS. We should make an effort to advocate for health promotion, including
      lifestyle modification, especially among the high-risk population and among
      residents in rural areas with limited medical resources. 

PMID- 24444539
TI  - Pioglitazone use and the risk of bladder cancer.
AB  - This study aimed to identify the risk association between pioglitazone exposure
      and bladder cancer. A nested case-control study was performed using a
      representative database randomly sampled from National Health Insurance
      enrollees. The source cohort consisted of newly diagnosed diabetic patients from
      1997 to 2009. Cases were identified as those with a diagnosis of bladder cancer
      from 2002 to 2009. For each case, four matched control individuals were randomly
      selected. A multiple logistic regression model was used to estimate the relative
      magnitude of risk in relation to the use of pioglitazone. In total, 259 cases and
      1036 controls were identified. The prevalent use of pioglitazone is similar in
      cases and controls (adjusted odds ratio, 1.20; 95% confidence interval, 0.58
      2.49). Compared to nonusers, these values were 1.08 (0.41-2.88) for those with
      cumulative pioglitazone use <= 8268 mg and 1.35 (0.48-3.79) for those with
      cumulative pioglitazone use > 8268 mg. This study does not provide support for
      the risk association between pioglitazone exposure and bladder cancer. Further
      confirmation is needed due to the limitation of small case number with relatively
      shorter exposure duration and lower cumulative dose. 

PMID- 24444540
TI  - Tea-drinking habit among new university students: associated factors.
AB  - The habit of drinking tea is highly prevalent in Asian countries. The aim of this
      study was to investigate the prevalence of tea drinking and to explore the
      correlated factors on tea drinking among young new students in the university,
      using a validated self-reported questionnaire. This study was carried out with
      5936 new students in a university in Taiwan. It comprised a self-administered
      structured questionnaire, including items related to personal and medical
      history, and lifestyle habits, using the Pittsburgh Sleep Quality Index (PSQI)
      and the 12-item Chinese Health Questionnaire (CHQ-12). Anthropometric
      measurements and laboratory tests were also performed. In total, 2065 (36.1%)
      students were in the tea-drinking group. Multiple logistic regression analysis
      showed the following factors were significant predictors of tea drinking:
      postgraduate students (p < 0.001), coffee drinking (p < 0.001), alcohol drinking
      (p < 0.001), minor mental morbidity (p = 0.009), poorer sleepers (p = 0.037),
      higher body mass index (p = 0.004), and sugar-sweetened beverage consumption (p <
      0.001). Our data showed that the tea-drinking habit was correlated with higher
      body mass index, which was contrary to the findings of a previous study. In
      clinical practice, perhaps we could consider more tea-drinking-related factors
      when we suggest tea consumption. 

PMID- 24444541
TI  - Paratesticular desmoplastic small round cell tumor with metastasis: a report of
      two cases.

PMID- 24444542
TI  - Enterogenous cyst of the ileum presenting as acute appendicitis.

PMID- 24444543
TI  - Torsade de pointes induced by amiodarone in a patient with heart failure.

PMID- 24444544
TI  - Recent advances in modeling languages for pathway maps and computable biological
      networks.
AB  - As our theories of systems biology grow more sophisticated, the models we use to
      represent them become larger and more complex. Languages necessarily have the
      expressivity and flexibility required to represent these models in ways that
      support high-resolution annotation, and provide for simulation and analysis that
      are sophisticated enough to allow researchers to master their data in the proper
      context. These languages also need to facilitate model sharing and collaboration,
      which is currently best done by using uniform data structures (such as graphs)
      and language standards. In this brief review, we discuss three of the most recent
      systems biology modeling languages to appear: BEL, PySB and BCML, and examine how
      they meet these needs. 

PMID- 24444545
TI  - Decision-making under risk is improved by both dopaminergic medication and
      subthalamic stimulation in Parkinson's disease.
AB  - Inconsistent findings regarding the effects of dopaminergic medication (MED) and
      deep brain stimulation (DBS) of the subthalamic nucleus (STN) on decision making
      processes and impulsivity in Parkinson's disease (PD) patients have been
      reported. This study investigated the influence of MED and STN-DBS on decision
      making under risk. Eighteen non-demented PD patients, treated with both MED and
      STN-DBS (64.3+/-10.2years, UPDRS III MED off, DBS off 45.5+/-17.1) were tested
      with the Game of Dice Task (GDT) which probes decision-making under risk during
      four conditions: MED on/DBS on, MED on/DBS off, MED off/DBS on, and MED off/DBS
      off. Task performance across conditions was compared analyzing two GDT
      parameters: (i) the "net score" indicating advantageous decisions, and (ii) the
      patient's ability to use negative feedback. Significantly higher GDT net scores
      were observed in Med on in contrast to Med off conditions as well as in DBS on
      versus DBS off conditions. However, no effect of therapy for the patient's
      ability to make use of negative feedback could be detected. The data suggest a
      positive influence of both MED and STN-DBS on making decisions under risk in PD
      patients, an effect which seems to be mediated by mechanisms other than the use
      of negative feedback. 

PMID- 24444546
TI  - Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR
      and regulating its upstream pathways.
AB  - Dihydromyricetin (DHM), a bioactive flavonoid compound extracted from the stems
      and leaves of Ampelopsis grossedentata, has oxidation resistance, anti-tumor and
      free radical scavenging capabilities. In this study, we found that DHM-induced
      autophagy inhibited the cell proliferation in HepG2 cells. The transmission
      electron microscopy results showed that DHM induced significantly autophagosome
      characteristics like autophagolysosome containing degraded cellular content. GFP
      labled LC3 plasma transfection showed that LC3 largely diffused to punctate
      structures with DHM treatment, while lysosomal-rich/acidic compartments detected
      using LysoTracker Red staining. In addition, DHM promoted the expressions of LC3
      II and Beclin-1 in a dose- and time-dependent manner. Further study showed that
      DHM suppressed the activation of mTOR (mammalian targets of rapamycin) involved
      in regulating its upstream signaling pathways including extracellular signal
      regulated kinase 1/2 (ERK1/2), AMPK (AMP-activated kinase) and class III
      phosphatidylinositol 3-kinase/phosphoinositide-dependent protein kinase 1/protein
      kinase B (PI3K/PDK 1/Akt) pathways. Taken together, all the results demonstrated
      that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells, the
      possible mechanism involved in inhibition of mTOR activation and regulating the
      related upstream signaling pathways. 

PMID- 24444547
TI  - Topical application of Gallic acid suppresses the 7,12-DMBA/Croton oil induced
      two-step skin carcinogenesis by modulating anti-oxidants and MMP-2/MMP-9 in Swiss
      albino mice.
AB  - Gallic acid (GA - 3,4,5-trihydroxybenzoic acid), a dietary anti-oxidant has been
      shown to inhibit cancer cell growth in in vitro. Herein, we investigated the in
      vivo chemo preventive activity of GA on 7,12-Dimethylbenz[a]anthracene
      (DMBA)/Croton oil induced two-step skin carcinogenesis in Swiss albino mice. Skin
      tumor incidence and tumor volume were recorded during the 16 weeks of
      experimental period. In addition, LDH-isozyme shift, skin collagen content,
      activities of matrix metalloproteinases (MMP-2/MMP-9) enzymes and enzymatic and
      non-enzymatic antioxidant were studied in the skin and serum of experimental
      mice. Tumor incidence was significantly increased in the DMBA/Croton oil induced
      mice (100%; p<0.001) when compared to GA co-treated mice (60%; p<0.01) and 5-FU
      treated mice (50%; p<0.01). Skin collagen content, MMPs activities, LDH
      isoenzymes and MMP-2/-9 expressions were increased in DMBA/Croton oil induced
      skin while decreased levels of enzymatic (GST, SOD, CAT & GPx) and non-enzymatic
      anti-oxidant (GSH) were noticed. On the other hand, GA co-treatment exhibited a
      significant protection by reverting back the altered levels of LDH-isoenzymes,
      antioxidants, collagen and MMP-2/MMP-9 activities. The results of this study
      indicate that topical application of GA inhibits DMBA/Croton oil induced two
      stage skin carcinogenic process by modulating the antioxidants and MMPs (-2 & -9)
      in the mouse skin.

PMID- 24444548
TI  - Sister chromatid exchange, (SCE), High-Frequency Cells (HFCs) and SCE
      distribution patterns in peripheral blood lymphocytes of Spanish adult smokers
      compared to non-smokers.
AB  - According to the International Agency for Research on Cancer, smoking tobacco is
      a major cause of cancer in humans. It causes about half of all male cancer deaths
      and an ever increasing number of cancer deaths in females. The aim of this study
      was to establish whether cigarette smoking increases sister chromatid exchanges
      (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light
      and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined
      and, the SCE distribution pattern among the chromosomes was analysed represented
      by a ratio described below. A local sample of 101 adult smokers (n=48) and non
      smokers (n=53), aged from 18 to 49 years, was studied using SCE levels in
      peripheral lymphocytes. Heavy smoking (>= 10 cigarettes per day) increased
      significantly the SCE frequency and the HFC parameters. Neither age nor sex
      significantly influenced the frequencies in the groups studied.

PMID- 24444549
TI  - A new disease allele for the p.C30071R mutation in titin causing hereditary
      myopathy with early respiratory failure.
AB  - Hereditary myopathy with early respiratory failure is an autosomal dominant
      myopathy caused by mutations in the 119th fibronectin-3 domain of titin. To date
      all reported patients with the most common mutation in this domain (p.C30071R)
      appear to share ancestral disease alleles. We undertook this study of two
      families with the p.C30071R mutation to determine whether they share the same
      haplotype as previously reported British families or whether the mutation arose
      as a de novo event. We sequenced the 119th fibronectin-3 domain in these two
      probands and flanking polymorphisms associated with the British haplotype in
      hereditary myopathy with early respiratory failure. A family of Indian descent
      had a haplotype that was not compatible with the British shared haplotype.
      Cloning of the 119th fibronectin-3 domain in this patient demonstrated
      polymorphisms rs191484894 and novel noncoding variant c.90225C>T on the same
      allele as the mutation, which is distinct from previously reported British
      families. This proves that the p.C30071R mutation itself (rather than the
      haplotype containing this mutation) causes hereditary myopathy with early
      respiratory failure and suggests its independent origin in different ethnic
      groups. 

PMID- 24444550
TI  - Utility of real-time three-dimensional echocardiography for Duchenne muscular
      dystrophy with echocardiographic limitations.
AB  - Duchenne muscular dystrophy (DMD) is strongly associated with a unique form of
      dilated cardiomyopathy. Cardiac complications are the leading cause of death in
      DMD; thus, longitudinal assessments and early intervention for cardiac
      dysfunction are necessary to improve prognosis. Two-dimensional echocardiography,
      which is routinely used for cardiac assessment, has some limitations for
      quantitative analyses in DMD patients with thoracic deformities and regional wall
      motion abnormalities in the left ventricle. Recently, real-time three-dimensional
      echocardiography has emerged as a feasible tool for cardiac assessment in various
      cardiac diseases. The aim of this study was to examine the utility of this
      technology in DMD. We evaluated left ventricular ejection fraction (LVEF), a
      major parameter of left ventricular function, in 17 male DMD patients. LVEF
      values measured by real-time three-dimensional echocardiography were compared
      with those determined by two established nuclear cardiology methods: "the first
      pass method of radionuclide angiocardiography" and "quantitative
      electrocardiogram-gated single-photon emission computed tomography". A good
      correlation was observed for LVEF values, particularly between real-time three
      dimensional echocardiography and "the first-pass method of radionuclide
      angiocardiography" (r=0.90, p<0.05). Thus, real-time three-dimensional
      echocardiography can provide an accurate measurement of LVEF in DMD patients with
      echocardiographic limitations. 

PMID- 24444551
TI  - Spousal loss and cognitive function in later life: a 25-year follow-up in the
      AGES-Reykjavik study.
AB  - The aim of this study was to investigate the associations between loss of a life
      partner and the development of dementia and decline in cognitive function in
      later life. We used an Icelandic cohort of 4,370 participants in the Age,
      Gene/Environment Susceptibility-Reykjavik Study who were living as married in
      1978 (born in 1907-1935) and were either still married (unexposed cohort) or
      widowed (exposed cohort) at follow-up (in 2002-2006). We ascertained history of
      marital status and spouse's death by record linkage to the Registry of the Total
      Population, Statistics Iceland. The outcome measures were as follows: 1) dementia
      and mild cognitive impairment; and 2) memory, speed of processing, and executive
      function. During the observation period, 3,007 individuals remained married and
      1,363 lost a spouse through death. We did not find any significant associations
      between loss of a spouse and our outcome variables, except that widowed women had
      poorer executive function (mean = -0.08) during the first 2 years after their
      husbands' deaths compared with still-married women (mean = 0.09). Our findings do
      not support the notion that the risk of dementia is increased following the loss
      of a spouse, yet women demonstrate a seemingly temporary decline in executive
      function following the death of a partner. 

PMID- 24444553
TI  - [Pay more attention to cytogenetics in prenatal diagnosis].

PMID- 24444552
TI  - Evaluation of recombinant LigB antigen-based indirect ELISA and latex
      agglutination test for the serodiagnosis of bovine leptospirosis in India.
AB  - Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus
      Leptospira, causing febrile infection characterized by multi-organ failure in
      humans and animals. Leptospiral Ig-like protein B (LigB) is a surface-expressed
      antigen that mediates host cell invasion or attachment. In this study, N-terminal
      conserved region of LigB protein (46 kDa) was evaluated for its diagnostic
      potential to detect anti-leptospiral antibodies in the sera of various animal
      species. Dot blot analysis revealed immunoreactivity of Leptospira-positive sera
      of cattle, buffalo, dog, sheep and goat to purified LigB protein. We have
      analyzed 1126 bovine serum samples, collected from Northern and Eastern part of
      India, by microscopic agglutination test (MAT) and recombinant LigB (rLigB) based
      ELISA and latex agglutination test (LAT). The sensitivity of rLigB based ELISA
      for 554 MAT positive sera was 96.9% and the specificity with 572 MAT negative
      sera was 91.08% whereas LAT showed sensitivity and specificity of 93.68% and
      92.31%, respectively. Kappa values of 0.879 and 0.860 for recombinant antigen
      based ELISA and LAT indicate excellent agreement with the gold standard
      serological test, MAT, for the detection of anti-leptospiral antibodies in sera.
      Further, LAT based on rLigB antigen is a simple and rapid test, suitable for
      serodiagnosis of leptospirosis under field conditions, owing to its portability
      and longer shelf life.

PMID- 24444554
TI  - [Association between fetal ventricular septal defects and chromosomal
      abnormalities].
AB  - OBJECTIVE: To evaluate the association between fetal ventricular septal defects
      (VSD) and chromosomal abnormalities. METHODS: The 214 fetuses diagnosed VSD in
      the First Affiliated Hospital of Sun Yat-sen University from January 2008 to
      September 2011 were included. The VSD were categorized into 3 types:
      perimembranous, muscular and mixed (the defect could not be classified because
      the dimensions were larger than 5 mm) type. The perimembranous defect was
      subdivided into inlet and outlet subtypes. Complicated with other cardiac
      abnormalities/extracardiac abnormalities or not, the cases were divided into
      isolated VSD group,VSD complicating cardiac anomalies group (other cardiac and/or
      great vessels malformation),VSD complicating extracardiac anomalies group
      (include organ malformation and sonographic soft markers) and VSD with both
      cardiac and extracardiac anomalies group.G-banding chromosome analysis was
      advised for all cases.In cases that no karyotype was obtained, the phenotype of
      the newborns was examined by the pediatricians. And those appeared normal were
      defined as normal karyotype. RESULTS: (1) There were 134 (62.6%, 134/214)
      perimembranous defects, including 91 (42.5%, 91/214) inlet lesions and 43 (20.1%,
      43/214) outlet lesions. There were 35 (16.4%, 35/214) muscular defects and 45
      (21.0%, 45/214) mixed type lesions. (2) Among the 214 VSD fetuses, 46 (21.5%)
      were isolated VSD, 34 (15.9%) were cases with other cardiac anomalies, 87 (40.6%)
      were cases with extracardiac anomalies and 47 (22.0%) were cases with both
      cardiac and extracardiac anomalies. (3) The chromosomal karyotypes were obtained
      in 105 cases, and 21 cases were considered as normal according to the
      phenotype.Of all these 126 cases, 46 (36.5%, 46/126) had chromosomal
      abnormalities. (4) Inlet defects had the highest risk of chromosomal
      abnormalities (28/55, 50.9%), while the muscular defects had the lowest risk
      (2/25, 8.0%). The incidence of chromosomal abnormalities in outlet and mixed type
      was 33.3% (9/27) and 7/19, respectively. The types of VSD were significantly
      correlated with chromosomal defects (P < 0.01).(5) The incidence of chromosomal
      abnormalities in the 4 groups were 3.4% (1/29), 2/14, 53.6% (30/56) and 48.1%
      (13/27), respectively. The risk of chromosomal abnormalities in the cases
      complicating extracardiac or both extracardiac and cardiac anomalies was
      significantly higher than the isolated VSD group (P < 0.01). CONCLUSION: Fetal
      VSD had a highest risk of chromosomal abnormalities, especially the inlet type
      and VSD with extracardiac abnormalities, and then the fetal karyotype should be
      recommended.

PMID- 24444555
TI  - [Prenatal diagnosis of agenesis of corpus callosum and its relationship with
      fetal chromosomal abnormalities].
AB  - OBJECTIVES: To evaluate prenatal imaging diagnosis of agenesis of corpus callosum
      and to investigate the relationship between ACC and chromosomal abnormalities.
      METHODS: Forty singleton pregnancies diagnosed ACC prenatally in Southern Medical
      University,Nanfang Hospital,General Hospital of Guangzhou Military Command of PLA
      and Shenzhen Maternity and Children Health Care Hospital from 2007 to 2012 were
      recruited. The correlation between ACC and chromosomal abnormalities, the
      consistence of sonographic characteristics and MRI diagnosis were analyzed
      retrospectively. RESULTS: (1) Among the 40 cases, 15 (38%, 15/40) were diagnosed
      isolated ACC, while 25 (63%, 25/40) were non-isolated ACC.In the non-isolated ACC
      cases, 18 (72%) had central nervous system abnormalities, including cerebellar
      vermis hypoplasia,Dandy-Walker syndrome, cerebellar cyst, holoprosencephaly,
      etc.Extra-CNS abnormalities were identified in 16 cases, including 5 cardiac
      abnormalities, 3 facial abnormalities, 2 congenital anomalies of urinary system,
      1 limb skeletal abnormality and 5 other congenital anomalies.(2) In the 40 cases,
      3 were chromosomal polymorphisms, including 2 cases of 46,XX, 1qh+ and 1 case of
      46,XY, 13cenh+. Chromosomal abnormalities were identified in 4 cases, including
      trisomy13, trisomy18, trisomy 21 and 47,XYY.(3) 36 cases(90%, 36/40) diagnosed by
      ultrasound were consistent with MRI, while 4 cases were different with MRI.37
      pregnancies were terminated, in which 28 cases were confirmed by fetal autopsy.3
      cases continued pregnancy and ACC was confirmed by postnatal MRI.(4) 25 non
      isolated ACC and 12 isolated ACC pregnancies were terminated. Among the 3
      isolated ACC cases that continued pregnancy, 2 were term delivery and 1 was
      premature delivery. All of them were confirmed by postnatal MRI.No mental or
      growth retardation was found during follow-up. CONCLUSION: MRI was prior to
      detect cases with non-isolated ACC and could be a supplementary method in the
      diagnosis and classification of ACC. Compared with isolated ACC, non-isolated ACC
      had a higher incidence of chromosomal abnormalities.

PMID- 24444556
TI  - [Study on several ultrasound markers combined maternal serum biochemical markers
      to screen fetal chromosomal aneuploidy at 11 to 13(+)6 weeks of gestation].
AB  - OBJECTIVE: To evaluate the efficiency of combined screening for chromosomal
      abnormalities in the first trimester and the ultrasound characteristics of these
      fetuses. METHODS: Retrospective study for 5000 singleton pregnancies by combined
      screening of trisomies 21, 18, 13 and Turner syndrome.Risk algorithms were
      developed for calculation of patient-specific risks for each of the three
      trisomies based on maternal age, fetal nuchal translucency, free beta human
      chorionic gonadotropin and serum pregnancy associated plasma protein A at 11 to
      13(+6) weeks of pregnant. The value of nuchal translucency (NT) and beta-hCG and
      pregnancy-associated plasma protein A (PAPP-A) level were inputted computer, and
      calculate the risk value ( >= 1: 270) by automatic analysis software. Two hundred
      and four cases with high risk were performed transabdominal chorionic villus
      biopsy to detect the fetal chromosomal karyotypes. Meanwhile, other ultrasonic
      characteristics of fetal were elevated. RESULTS: (1) Five thousand cases of
      pregnant women were detected, including 4983 normal cases, 62 cases were induced
      labor for a variety of reasons in the second trimester, including 40 cases with
      normal karyotype but with congenital heart disease, 17 cases of chromosome
      abnormalities (9 cases trisomy 21, 2 cases trisomy 18, 1 cases trisomy 13, 4
      cases 45X), 2 cases spina bifida, 2 cases digestive tract obstruction, 1 cases
      giant bladder.One case with low risk of fetal chromosomal abnormalities in
      combined screening, but high risk of age (maternal age were over 40 years old),
      it was 21 trisomy syndrome after the prenatal diagnosis.(2) Five cases of nasal
      bone loss in 9 cases of trisomy 21 (5/9), 5 cases with three tricuspid
      regurgitation (5/9), 4 cases of venous ductus a wave flow reverse (4/9), 3 cases
      of fetal nasal bone loss accompanied by tricuspid regurgitation and venous ductus
      a wave flow reverse (3/9).One case of nasal bone loss in 2 cases of trisomy 18, 2
      cases were tricuspid regurgitation and venous ductus a wave flow reverse. Two
      cases in 4 cases of 45X had venous ductus a wave flow reverse. There were 8 cases
      (0.16%) nasal bone absence in 4983 cases of normal karyotype fetus, 48 cases
      (0.96%) of tricuspid regurgitation and 44 cases (0.88%) of venous ductus a wave
      flow reverse. Thirty-two cases in 40 cases (80%) of fetal congenital heart
      disease were tricuspid regurgitation, 30 cases of venous ductus a wave flow
      reverse (75%).Eight cases of nasal bone absence normal karyotype fetus were found
      the nasal bone at 20 weeks gestation. CONCLUSION: Combination screening of nuchal
      translucency with serum markers in the first trimester were high detection rate
      and low false positive rate; a wave reversion and fetal nasal bone absence
      accompanied by tricuspid regurgitation can improve the detection rate of abnormal
      karyotype; abnormalities ultrasound marker may be associated with fetal
      congenital heart disease at 11-13(+6) weeks of pregnancy.

PMID- 24444557
TI  - [Value of nuchal translucency thickening in the fetal chromosome abnormality
      screening].
AB  - OBJECTIVE: To investigate the value of nuchal translucency(NT) thickening in the
      fetal chromosome abnormality screening. METHODS: The 14 881 pregnant women
      received NT measurement in 11-13(+)6 weeks at Beijing Obstetrics and Gynecology
      Hospital from January 2010 to August 2012. The 118 fetuses whose NT >= 2.5 mm
      were recruited.One hundred and eight (91.5%, 108/118) of them accepted invasive
      procedure and karyotype analysis. RESULTS: (1) Chromosome karyotype analysis: 113
      singleton pregnancies (95.8%) and 5 twin pregnancies (4.2%) whose NT thickened
      from 2.5 mm to 11.0 mm were advised karyotype analysis. The 108 pregnant women
      accepted karyotype analysis. Among them, 88 had normal chromosome karyotype, and
      20 had chromosome abnormalities. The detection rate was 18.5% (20/108).(2) The
      sensitivity, specificity, false positive rate, false negative rate, total
      consistent rate, positive predictive value and negative predictive value of
      prenatal screening of chromosome abnormalities for NT >= 2.5 mm were 44%, 99%,
      1%, 56%, 99%, 19% and 100%, respectively.(3) Among the 88 fetuses who had normal
      karyotype, 72 (82%) had isolated thickened NT, while 16 (18%) had fetal
      structural malformation or intrauterine demise.(4) Among the 10 pregnant women
      who did not accept fetal karyotype analysis, 8 terminated pregnancy because of
      fetal structural malformation, and the other 2 fetuses died in uterus.(5) All of
      the 5 twin pregnancies were dichorionic twins, and one of the twins had thickened
      NT. Among the 5 twin pregnancies, one fetus was trisomy 21 and others had normal
      karyotype.3 twin pregnancies who had normal chromosomes gave live birth. And the
      other had a gastroschisis and exstrophy deformity fetuse. This fetuse died in
      uterus and remaining fetuse had full-term live birth.(6) 35 (29.7%) pregnant
      women received second trimester Down's syndrome serum screening.One was high risk
      and was proved a trisomy 21 pregnancy. Thirty-four were low risk and had normal
      chromosome karyotype. CONCLUSION: NT thickening may indicate fetal chromosome
      abnormalities or other structural malformations. It is a useful prenatal
      screening indicator.

PMID- 24444558
TI  - [Prenatal diagnosis of 22q11.2 microdeletion by multiplex ligation-dependent
      probe amplification].
AB  - OBJECTIVE: To explore the clinical value of multiplex ligation-dependent probe
      amplification (MLPA) technique performed in prenatal diagnosis of chromosome
      22q11.2 microdeletion. METHODS: MLPA was performed to detect chromosome 22q11.2
      mircodeletion in 62 fetuses with congenital heart defects by fetal
      echocardiography and a normal karyotype by standard G-banding analysis.For a
      22q11.2 mircodeletion fetus, his parents were detected to know if it is inherited
      or de novo. The microdeletion was confirmed by array-based comparative genomic
      hybridization (arrayCGH). RESULTS: MLPA revealed five 22q11.2 mircodeletions in
      the 62 fetuses, and the positive detection rate was 8% (5/62). Among these, 4
      cases carried the 3M typically deletion which all are de novo, and 1 case carried
      the 1.5M non-typically deletion which was inherited from his father.arrayCGH
      confirmed the 22q11.2 microdeletions and delineated the precise location and size
      of microdeletions. CONCLUSION: MLPA has clinical value in prenatal diagnosis of
      22q11.2 mircodeletion, which could provide important genetic information for
      genetic consulting, pregnancy management and intervention after birth.

PMID- 24444559
TI  - [Clinical study on echocardiography combined with end-tidal CO2 monitoring in
      preventing the venous air embolism during operative hysteroscopy].
AB  - OBJECTIVE: To explore the value of transthoracic echocardiography(TTE) combined
      with partial pressure of end-tidal CO2 (P ETCO2) monitoring in preventing venous
      air embolism(VAE) during hysteroscopy operation. METHODS: From August 2010 to
      August 2012, 300 cases undergoing hysteroscopic surgery under general anaesthesia
      were enrolled in this study. With the echocardiography combined with P ETCO2
      monitoring during hysteroscopic surgery, the time of VAE appearing in the right
      atrium , the extent of air embolism(grade 0-4), the changes of P ETCO2,
      peripheral oxygen saturation (SpO2), blood pressure (Bp), the amount of fluid
      intravasation and the blood loss were recorded in detail . Take the 24 cases that
      the grades of VAE in grade 3 or above and a decrease in P ETCO2 >= 5 mm Hg (1 mm
      Hg = 0.133 kPa) as intervention group. Stop operation immediately, the left side
      and raise your right shoulder, oxygen inhalation and dexamethasone 10 mg
      intravenous drip were given to the intervention group; the control group (5 cases
      in grade 3 or above and a decrease in P ETCO2<5 mm Hg) only stop operation
      immediately, observation patient's condition closely. RESULTS: (1) The occurrence
      of VAE: air embolism occurred in 34 patients among all 300 patients, all of 34
      patients had evidence of gas embolism in the inferior vena cava, right atrium(RA)
      and right ventricle chamber, and 29 patients had evidence of continuous groups of
      gas emboli. There were 32 cases with the decrease in P ETCO2 > 2 mm Hg, 14 cases
      with SpO2 less than 95%, and 4 cases with a drop in Bp >= 20%. (2) The change of
      the decrease of P ETCO2 and the grades of VAE: the decrease of P ETCO2 and the
      grades of VAE were positively correlated (r = 0.601, P < 0.01), continuous groups
      of gas emboli signal in RA, when the drop of P ETCO2 >= 5 mm Hg, 8 of the 34
      cases whose drop of P ETCO2 >= 10 mm Hg, 7 cases in grades 4. The decrease of P
      ETCO2 [(7.5 +/- 2.4) mm Hg versus (11.1 +/- 4.1) mm Hg], the amount of fluid
      intravasation[(688 +/- 150) ml versus (925 +/- 268) ml] and the blood loss[(71 +/
      36) ml versus (127 +/- 56) ml] all had statistical difference in grade 3 and 4
      (P < 0.05) . The sensitivity of P ETCO2 was better than SpO2 and Bp in detecting
      of VAE. (3) The cases of P ETCO2 continue to decline and recovery time between
      the two groups:2 cases' P ETCO2 continued to decline in the intervention group,
      but 4 cases in the control group. The recovery time of the two groups was (4.8 +/
      1.6) and (8.3 +/- 1.9) min, respectively, which reached statistical difference
      between (P < 0.05). CONCLUSIONS: TTE combined with P ETCO2 monitoring can
      effectively predict the occurrence of air embolism in hysteroscopic surgery;
      Continuous groups of gas emboli signal in RA accompanied by a decrease in P ETCO2
      >= 5 mm Hg indicates that the occurrence of air embolism; the more the amount of
      intravasation of distension fluid and the blood loss, the more the air into the
      body. Timely intervention can effectively prevent the development of air embolism
      when the VAE in grade 3 or above accompanied by a decrease in P ETCO2 >= 5 mm Hg.

PMID- 24444560
TI  - [Comparison of the efficiency between in-vitro maturation and in-vitro
      fertilization after early follicular phase GnRH agonist down-regulation in
      infertile women with polycystic ovary syndrome].
AB  - OBJECTIVE: To compare the outcomes of in-vitro maturation (IVM) and in-vitro
      fertilization (IVF) after early follicular phase gonadotropin-releasing hormone
      agonist (GnRH-a) down-regulation in infertile patients with polycystic ovary
      syndrome (PCOS). METHODS: From July 2010 to December 2012, 72 infertile patients
      with PCOS undergoing assisted reproductive technology treatment in the Affiliated
      First Hospital of Wenzhou Medical University were enrolled in this study. The
      patients were divided into 2 groups, which were patients with early follicular
      phase down-regulation IVM (36 cases) at IVM group and early follicular phase down
      regulation long protocol IVF (36 cases) at IVF group. The laboratory parameters
      and clinical outcomes were compared between two groups. RESULTS: (1) Lab
      parameters: a total of 442 oocytes were retrieved in group IVM, and 560 were in
      group IVF. The rate of mature oocytes of 83.8% (469/560) and high-quality embryos
      of 70.9% (212/299) at group IVF were significantly higher than that of group
      IVM[54.1% (239/442) and 50.7% (73/144), retrospectively, P < 0.01]. In group IVM,
      the average duration of gonadotropin (Gn) was (2.8 +/- 1.5) days and the average
      dosage of Gn was (285 +/- 169) U, which were significantly lower than (11.0 +/-
      1.0) days and (1499 +/- 165) U in group IVF (P < 0.01). The mean number of
      oocytes retrieved 12.8 +/- 2.5, fertilization rate of 64.8% (155/239), and
      implantation rate of 31% (23/74) in group IVM and 15.6 +/- 3.1, 65.5% (307/469),
      31% (23/74) in group IVF, which did not reach statistical difference (P > 0.05) .
      (2) Clinical outcomes: the clinical pregnancy rate (17/31, 55%) of IVF group was
      not significantly higher than that 44% (14/32) at IVM group (P > 0.05). The
      abortion rate was 1/17 at Group IVF and 1/14 in group IVM, which did not show
      statistical difference. Women at IVM group has no ovarian hyper-stimulation
      syndrome (OHSS) cycle, group IVF has 31% (11/36) cycles presented moderate and
      severe OHSS. CONCLUSIONS: Infertile patients with PCOS undergoing IVM and IVF
      treatment after early follicular phase GnRH-a down-regulation can get
      satisfactory laboratory and clinical outcome. In addition to short treatment
      cycle, IVM can also avoid the occurrence of OHSS completely, but it has a rising
      trend in the abortion rate. IVF has a high incidence of OHSS, meanwhile, it
      increases the dosage of gonadotropins.

PMID- 24444561
TI  - [Effect of domestic highly purified urinary follicle stimulating hormone on
      outcomes of in vitro fertilization-embryo transfer in controlled ovarian
      stimulation].
AB  - OBJECTIVE: To investigate the effect of domestic urine-derived high-purity
      follicle- stimulating hormone (HP-FSH, Lishenbao) on the outcome of in vitro
      fertilization(IVF) embryo transfer (ET) in controlled ovarian stimulation (COS).
      METHODS: From 1 September 2010 to 31 March 2011, total of 3178 infertility
      patients from 14 Reproductive Center with IVF or intracytoplasmic sperm injection
      (ICSI) indications who accepted first IVF or ICSI cycle were studied
      retrospectively. Their causes of infertility include all infertility factors
      except ovulatory dysfunction infertility and uterine factor infertility. The only
      long luteal phase gonadotropin-releasing hormone agonist (GnRH-a) protocol was
      included. Patients were divided into 2 groups according to the type of follicle
      stimulating hormone (FSH) agents used: 1932 cases in HP-FSH group and 1246 cases
      in recombinant FSH (rFSH)group. Patients in both groups were combined with human
      menopausal gonadotropin (hMG) at doses of 150 U when follicle with diameter
      reached to 14-16 mm. When 3 dominate follicle with diameter reached 18 mm, hCG at
      dose of 5000 to 10 000 U or recombinant hCG at dose of 250 ug was administered by
      intramuscular injection. After 34 to 36 hours, oocytes were obtained guided by
      ultrasound, then IVF-ET were underwent in their Reproductive Center. The primary
      endpoint was comparison of live birth rate between the two groups. The secondary
      endpoints were comparisons of clinical pregnancy rate, miscarriage rate, and
      implantation rate, as well as COS and IVF outcome between the two groups.
      RESULTS: (1) There were significantly differences in baseline characteristics of
      the patients between two groups. The mean age was elder(32 +/- 4 versus 30 +/- 4,
      P < 0.01) , the infertility duration was longer (5 +/- 4 versus 5 +/- 3, P <
      0.01) , and antral follicle count (AFC) was less (11 +/- 5 versus 13 +/- 7, P <
      0.01) in patients of HP-FSH group compared with those in patients of rFSH group.
      (2) As compared with rFSH, the total doses of gonadotropin needed was (2348 +/-
      1011) U in HP-FSH group versus (2022 +/- 659) U in rFSH group, the number of
      oocytes 13 +/- 6 in HP-FSH group and 14 +/- 7 in rFSH group, the rate of embryo
      frozen cycle of 66.30% (1281/1932) in HP-FSH group and 74.88% (933/1246) in rFSH
      group, which all reached statistical difference (P < 0.01). However, there were
      no significant different implantation rate [30.49% (1111/3644) versus 32.45%
      (737/2271)] between two groups. The other clinical parameters did not show
      significant difference, including clinical pregnancy rate per started cycle
      [41.61% (804/1932) versus 41.97% (523/1246) ] , clinical pregnancy rate per ET
      cycle[46.58% (804/1726) versus 48.47% (523/1079)], live birth rate per started
      cycle[34.21% (661/1932) versus 34.19% (426/1246)], live birth rate per ET cycle
      [38.30% (661/1726) versus 39.48% (426/1079)], miscarriage rate[13.6% (109/804)
      versus 16.4% (86/523)], and moderate/severe ovarian hyperstimulation syndrome
      (OHSS) rate [5.80% (112/1932) versus 7.78% (97/1246)](P > 0.05).(3) Treatment
      cost: the cost of gonadotropins needed for the patients in HP-FSH group was lower
      than that in rFSH group (4005 +/- 1650 versus 6482 +/- 2095, P < 0.01).
      CONCLUSION: In IVF/ICSI treatment cycles, domestic HP-FSH has similar live birth
      rate and lower financial burden when compared with rFSH.

PMID- 24444562
TI  - [Analysis of epidermal growth factor receptor expression and gene expression
      status in tissue microarray of cervical squamous cell carcinoma].
AB  - OBJECTIVE: To elucidate the protein expression and gene expression status and the
      relationship between epidermal growth factor receptor (EGFR) protein expression
      and EGFR gene status. METHODS: Tissue microarray containing 72 cervical squamous
      cell carcinoma tissues was constructed, and EGFR protein expression and gene
      status were evaluated by immunohistochemical and fluorescence in situ
      hybridization (FISH) techniques. RESULTS: Protein expression of EGFR: 69 of 72
      cervical squamous cell carcinomas were observed. The results demonstrated it was
      significant association with invasion depth, lymph node metastasis and lymph
      vessel invasion (chi(2) = 4.998, P < 0.05; chi(2) = 4.299, P < 0.05; chi(2) =
      4.686, P < 0.05) in cervical squamous cell carcinomas. For FISH assessing EGFR
      gene, 64 of 72 carcinomas were observed; 7 of 64 cases showed EGFR gene
      amplification, and 25 disomy, 23 trisomy and 9 polysomy were detected. There were
      high levels of protein expression in all the EGFR gene amplification cases, and
      there were significant association between EGFR protein expression and the gene
      copy number (chi(2) = 13.564, P < 0.05). CONCLUSIONS: EGFR may participate in the
      occurrence, progression and metastasis of cervical squamous cell carcinoma.
      Overexpression of EGFR protein may result from gene amplification and gene copy
      number increases, which showed that EGFR gene expression status may be a more
      effective biological indicator of cervical squamous cell carcinoma targeted
      therapy.

PMID- 24444563
TI  - [Polymorphisms of ERCC1 gene and outcomes in epithelial ovarian cancer patients
      with platinum-based chemotherapy].
AB  - OBJECTIVE: To explore the relationship among single nucleotide polymorphism (SNP)
      of excision repair cross-complementing 1(ERCC1) gene, chemotherapy sensitivity
      and clinical outcomes of epithelial ovarian cancer (EOC) patients treated with
      platinum. METHODS: Six tag single nucleotide polymorphisms (tagSNP;rs11615,
      rs3212986, rs735482, rs3212955, rs12610134 and rs3212958) were chose from ERCC1
      gene. The genotypes of 6 tagSNP were determined by Snapshot method in 220 EOC
      patients. Primary clinical outcomes parameter contained EOC patients' responses
      to platinum-based chemotherapy, progression-free survival (PFS) and overall
      survival (OS) were analysed. RESULTS: The rs11615 C/T SNP of ERCC1, CC, CT and TT
      genotype frequencies were 53.1%, 45.6%, 1.4% in responders to platinum-based
      chemotherapy, while 52.0%, 35.6%, 12.3% in non-responders, respectively, in which
      there was significant difference between the two groups (P = 0.002) . Compared
      with the patients with CC genotype, the patients carrying TT genotype had a
      significantly poor response to platinum-based chemotherapy (OR = 6.22, 95%CI:1.12
      34.42). Similarly, the genotypes frequencies distribution of rs11615 C/T SNP of
      ERCC1 was different between the recurrence and non-recurrence group, death and
      survival group (all P < 0.05). Kaplan-Meier survival analysis showed that the
      genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was associated
      with PFS and OS (P < 0.01) of EOC patients. Cox's multivariate analysis suggested
      that patients with TT genotype had a shorter PFS (HR = 2.19, 95%CI:1.14-4.22, P =
      0.009) and OS (HR = 2.22, 95%CI:1.06-4.64, P = 0.021) compared with those
      carrying CC genotype [adjusting for age, International Federation of Gynecology
      and Obstetrics (FIGO) stage, pathological type, grade and tumor residual size].
      The genotypes frequencies distribution of rs3212986, rs735482, rs3212955,
      rs12610134 and rs3212958 SNP of ERCC1 did not show the significant difference
      between the responders to platinum-based chemotherapy and non-responders. The
      other 5 tagSNP may not be associated with the PFS and OS of EOC patients (all P >
      0.05). CONCLUSION: The rs11615 SNP of ERCC1 may become a valuable prognostic
      biomarker for EOC patients treated with platinum-based chemotherapy.

PMID- 24444564
TI  - [Interaction mechanism and influence between fatty acid oxidation in trophoblast
      cells and p38MAPK signal transduction pathway of severe preeclampsia].
AB  - OBJECTIVE: To investigate the effects of expression of mitochondria long-chain
      fatty acid oxidative enzyme (long-chain 3 hyroxyacyl CoA dehydrogenase, LCHAD)
      and p38 mitogen activated protein kinase (p38MAPK) signal transduction pathway in
      severe preeclampsia. METHODS: Serum-free trophoblast cells cultured in vitro were
      stimulated by early onset severe preeclampsia serum (E-PE group), late onset
      severe preeclampsia serum (L-PE group), HELLP syndrome serum (HELLP group), and
      normal pregnancy serum (NP group) respectively; each group was added DMEM/F12
      medium, reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase inhibitor (NADPH-I) and p38MAPK inhibitor (p38-I) to stimulate cells.
      Expression of mRNA and protein of LCHAD in trophoblast cells were detected by
      real-time PCR and western blot. RESULTS: (1)The expression of mRNA of LCHAD: the
      level of mRNA of LCHAD in NP+DMEM, E-PE+DMEM, E-PE+NADPH-I, E-PE+p38-I, L
      PE+DMEM, L-PE+NADPH-I, L-PE+p38-I and HELLP+DMEM, HELLP+NADPH-I, HELLP+p38-I
      groups were 1.00 +/- 0.03, 0.14 +/- 0.08, 0.95 +/- 0.20, 1.43 +/- 1.02, 0.37 +/-
      0.18, 1.51 +/- 0.36, 1.60 +/- 0.31, 0.10 +/- 0.04, 0.49 +/- 0.10, 0.44 +/- 0.21,
      respectively. The relative expressions of mRNA of LCHAD were significantly
      reduced in E-PE+DMEM, L-PE+DMEM and HELLP+DMEM groups compared with the NP+DMEM
      group (P < 0.05). Compared with the NP groups, the relative expressions of mRNA
      of LCHAD were significantly increased in L-PE+NADPH-I and L-PE+p38-I group (P <
      0.05), while reduced in HELLP groups(P < 0.05). (2) The expression of protein of
      LCHAD: the relative expressions of protein of LCHAD in NP+DMEM, E-PE+DMEM, E
      PE+NADPH-I, E-PE+p38-I, L-PE+DMEM, L-PE+NADPH-I, L-PE+p38-I and HELLP+ DMEM,
      HELLP+NADPH-I, HELLP+p38-I groups were 19.4 +/- 2.2, 10.7 +/- 1.1, 17.9 +/- 3.3,
      19.1 +/- 2.9, 16.4 +/- 2.3, 20.3 +/- 2.3, 20.9 +/- 4.3, 12.4 +/- 2.3, 17.6 +/-
      2.6, 17.7 +/- 2.0 respectively. Compared with the NP groups, the protein
      expressions of LCHAD were significantly remarkably reduced in E-PE+DMEM, L
      PE+DMEM and HELLP groups (P < 0.05). Compared with the DMEM groups, the protein
      expressions of LCHAD were significantly increased in NADPH-I and p38-I groups of
      E-PE, L-PE and HELLP groups (P < 0.05). CONCLUSIONS: These studies demonstrate
      that long chain fatty acid oxidation was involved in the pathogenesis and
      development of preeclampsia. The expressions of gene and protein of LCHAD were
      remarkably affected by early onset severe preeclampsia and HELLP syndrome. NADPH
      I and p38-I may allay the disorder of fatty acid oxidation. p38MAPK signal
      transduction pathway may contributed in this process.

PMID- 24444565
TI  - [Effects of controlled ovarian hyperstimulation on mitochondria copy number and
      functions in murine oocytes].
AB  - OBJECTIVE: To investigate the effect of whether controlled ovarian
      hyperstimulation (COH) on mitochondrial DNA (mtDNA) copy number, mitochondrial
      function, distribution, the level of reactive oxygen species (ROS) in oocytes and
      the mechanism of oocyte loss in COH. METHODS: Matured murine oocytes were
      classified into COH group and natural cycles (NC) group. The copies of mtDNA, the
      magnitude of mitochondrial membrane potential (Deltaphim) and oocyte adenosine
      triphosphate (ATP) content, pattern of mitochondrial distribution, and ROS levels
      were evaluated by realtime PCR, immunofluorescence and fluorescence-luciferase
      mensuration. RESULTS: The copies of mtDNA, the levels of Deltaphim, and ATP
      content in oocytes between COH and NC groups showed statistical difference [(1.15
      +/- 0.01)*10(5), 0.34 +/- 0.03 and (241 +/- 20) fmol/oocyte (COH)] versus [(2.15
      +/- 0.19)*10(5), 0.82 +/- 0.07 and (325 +/- 11) fmol/oocyte (NC)], respectively(P
      < 0.05). However, there were no significant differences in the rate of evenly
      distributed mitochondria and the level of ROS in oocytes from COH and NC [(76.5%
      (78/102) in COH versus 82.1% (69/84)]; 1.07 +/- 0.07 in COH versus 0.93 +/- 0.08
      in NC (P > 0.05). CONCLUSION: It was indicated that non-physiological COH
      treatments inhibit mtDNA replication, alter mitochondrial function, which might
      partly be involved in the low development potential of COH oocyte.

PMID- 24444567
TI  - Are modern dual mobility cups a valuable option in reducing instability after
      primary hip arthroplasty, even in younger patients?
AB  - Hip instability after total hip replacement has been shown to be a critical cause
      of failure. The use of dual mobility has been classically restricted to patients
      "at risk", over 70 years of age. The question rises up about extended indications
      of so-called "modern" second generation dual mobility cups. This prospective
      multicenter study reports on first results at 2-5 years of the HA anatomical ADM
      cup upon two comparative groups of patients under 70 years (112 hips) vs. over 70
      years of age (325 hips). No dislocation, migration, tilting, wear, or intra
      prosthetic dislocation was recorded within each of the two cohorts. Survivorship
      for cup failures at this 4-year period was ideal at 100% in the younger patients,
      and 99.7% in the older group of patients.

PMID- 24444566
TI  - Maximising students' use of purpose-built shade in secondary schools:
      quantitative and qualitative results of a built-environment intervention.
AB  - A trial installing shade sails at secondary schools found increased students' use
      of newly shaded areas, but relatively low use overall. We examined site features
      and weather related to use of these shaded areas. Tables with seats and
      temperatures >=27 degrees C increased student use of shaded areas, presence of
      grass decreased use. Focus groups at eight schools suggest students were unaware
      of changes to their habitual use of favoured locations. Results infer careful
      selection of locations for built-shade and provision of tables with seats will
      assist in maximising student use and investments in shade sails. 

PMID- 24444568
TI  - Early failures in total hip arthroplasty -- a changing paradigm.
AB  - Between 2001 and 2011, 1168 revision hip arthroplasties were reviewed for "early"
      failures within 5 years of the primary total hip arthroplasty (THA). 24.1%
      underwent revision within 5 years of index THA. Aseptic loosening, infection,
      instability, metallosis, and fracture were common modes of failure. In our
      previous report from 1986 to 2000, 33% were "early" revisions, with instability
      and aseptic loosening accounting for over 70% of these early failures. While the
      proportion of "early" revisions decreased 9% from our previous report, this rate
      remains alarming. The emergence of metallosis and aseptic loosening of monoblock
      metal on metal shells as leading causes of early failures is concerning. This
      report suggests caution in the early adoption of new innovations before evidence
      based medicine is available to justify the risk of their use.

PMID- 24444569
TI  - Fractures of a single design of highly cross-linked polyethylene acetabular
      liners: an analysis of voluntary reports to the United States Food and Drug
      Administration.
AB  - Polyethylene liner fracture is a risk associated with the use of highly cross
      linked UHMWPE. We performed a review of the voluntary reports of fractured liners
      to the US Food and Drug Administration to determine if any risk factors could be
      identified. There have been 74 reports of fractured Trilogy, Longevity liners to
      the US Food and Drug Administration since 1999. Most cases utilized small
      acetabular shells (<=54 mm) combined with large diameter heads (>=36 mm). Liners
      less than 7 mm thick at the weight bearing or 4.8 mm thick at the rim should be
      used with caution. At revision surgery, malpositioned shells should be revised
      and the use of a thin liner should be avoided.

PMID- 24444570
TI  - Use of stepped porous titanium metaphyseal sleeves for tibial defects in revision
      total knee arthroplasty: short term results.
AB  - Stepped porous titanium metaphyseal sleeves may provide an option for enhanced
      fixation in managing challenging tibial defects in revision total knee
      arthroplasty (TKA). We retrospectively reviewed data on 51 patients who underwent
      revision TKA utilizing a metaphyseal sleeve for Anderson Orthopaedic Research
      Institute (AORI) Type II and III tibial defects between June 2007 and July 2011.
      Of these 51 patients, 36 patients had complete clinical and radiographic data. At
      final follow-up (mean: 38 months) significant improvements in knee range of
      motion and Knee Society scores were observed postoperatively (P < 0.001). Four
      revision procedures were necessary, but none for aseptic implant fixation
      failure. Radiographic review at final follow-up revealed stable, osteointegrated
      components without component migration or clinically significant osteolysis.
      Metaphyseal sleeve use in the management of moderate to severe tibial defects in
      revision TKA resulted in satisfactory clinical outcomes and is a versatile option
      for achieving stable fixation.

PMID- 24444571
TI  - NPs, shorter training needed to fix workforce shortage in primary care.

PMID- 24444573
TI  - Screening for coronary heart disease with electrocardiography.

PMID- 24444574
TI  - Non-celiac gluten sensitivity: important diagnosis or dietary fad?

PMID- 24444575
TI  - Anemia and mucocutaneous telangiectasias.

PMID- 24444576
TI  - Common questions about Barrett esophagus.
AB  - Barrett esophagus is a precancerous metaplasia of the esophagus that is more
      common in patients with chronic reflux symptoms, although it also occurs in
      patients without symptomatic reflux. Other risk factors include smoking, male
      sex, obesity, white race, hiatal hernia, and increasing age (particularly older
      than 50 years). Although Barrett esophagus is a risk factor for esophageal
      adenocarcinoma, its management and the need for screening or surveillance
      endoscopy are debatable. The annual incidence of progression to esophageal cancer
      is 0.12% to 0.33%; progression is more common in patients with high-grade
      dysplasia and long-segment Barrett esophagus. Screening endoscopy should be
      considered for patients with multiple risk factors, and those who have lesions
      with high-grade dysplasia should undergo endoscopic mucosal resection or other
      endoscopic procedures to remove the lesions. Although the cost-effectiveness is
      questionable, patients with nondysplastic Barrett esophagus can be followed with
      endoscopic surveillance. Lowgrade dysplasia should be monitored or eradicated via
      endoscopy. Although there is no evidence that medical or surgical therapies to
      reduce acid reflux prevent neoplastic progression, proton pump inhibitors can be
      used to help control reflux symptoms. 

PMID- 24444577
TI  - Celiac disease: diagnosis and management.
AB  - Celiac disease is an autoimmune disorder of the gastrointestinal tract. It is
      triggered by exposure to dietary gluten in genetically susceptible individuals.
      Gluten is a storage protein in wheat, rye, and barley, which are staples in many
      American diets. Celiac disease is characterized by chronic inflammation of the
      small intestinal mucosa, which leads to atrophy of the small intestinal villi and
      subsequent malabsorption. The condition may develop at any age. Intestinal
      manifestations include diarrhea and weight loss. Common extraintestinal
      manifestations include iron deficiency anemia, decreased bone mineral density,
      and neuropathy. Most cases of celiac disease are diagnosed in persons with
      extraintestinal manifestations. The presence of dermatitis herpetiformis is
      pathognomonic for celiac disease. Diagnosis is supported by a positive tissue
      transglutaminase serologic test but, in general, should be confirmed by a small
      bowel biopsy showing the characteristic histology associated with celiac disease.
      The presence of human leukocyte antigen alleles DQ2, DQ8, or both is essential
      for the development of celiac disease, and can be a useful genetic test in select
      instances. Treatment of celiac disease is a gluten-free diet. Dietary education
      should focus on identifying hidden sources of gluten, planning balanced meals,
      reading labels, food shopping, dining out, and dining during travel. About 5% of
      patients with celiac disease are refractory to a gluten-free diet. These patients
      should be referred to a gastroenterologist for reconsideration of the diagnosis
      or for aggressive treatment of refractory celiac disease, which may involve
      corticosteroids and immunomodulators. 

PMID- 24444578
TI  - Diagnostic approach to patients with tinnitus.
AB  - Tinnitus, a common symptom encountered in family medicine, is defined as the
      perception of noise in the absence of an acoustic stimulus outside of the body.
      Because tinnitus is a symptom and not a disease, its underlying cause must be
      determined to best help patients. Although tinnitus is often idiopathic,
      sensorineural hearing loss is the most common identified cause. It can also be
      caused by other otologic, vascular, neoplastic, neurologic, pharmacologic,
      dental, and psychological factors. More serious causes, such as Meniere disease
      or vestibular schwannoma, can be excluded during the evaluation. History and
      physical examination of the head, eyes, ears, nose, throat, neck, and neurologic
      system guide subsequent evaluation. Almost all patients with tinnitus should
      undergo audiometry with tympanometry, and some patients require neuroimaging or
      assessment of vestibular function with electronystagmography. Supportive
      counseling should begin during the initial evaluation to help patients cope with
      tinnitus. Counseling may also improve the chances of successful subsequent
      treatment. 

PMID- 24444580
TI  - Dementia.

PMID- 24444581
TI  - Is intensive blood pressure control beneficial in patients with acute
      intracerebral hemorrhage?

PMID- 24444588
TI  - Celiac disease.

PMID- 24444582
TI  - FPIN's Clinical Inquiries. Methylphenidate for management of fatigue in the
      palliative care setting.

PMID- 24444589
TI  - Tinnitus.

PMID- 24444590
TI  - Nonlinear photocurrent with a threshold of excitation density induced by the long
      range electron-electron interaction in the charge-ordered molecular conductor
      (BEDT-TTF)3(ClO4)2.
AB  - We investigated a photoexcited state in the molecular conductor (BEDT
      TTF)3(ClO4)2 (BEDT-TTF = bis(ethylenedithio)tetrathiafulvalene) with charge
      localization due to the electron-electron Coulomb interaction. Photocurrent
      induced by intramolecular excitation was observed in a charge-ordered insulating
      state. As a result, nonlinear photocurrent with a threshold of excitation light
      density was experimentally obtained. The threshold decreased as the temperature
      increased. This nonlinear photocurrent indicates a transition from an excitonic
      state to a free excited electronic state. The excitonic state below the threshold
      is formed by the long-range electron-electron Coulomb interaction. In the free
      excited electronic state above the threshold, high-density photoexcitation
      induces Coulomb screening, which results in exciton dissociation and a free
      electronic state.

PMID- 24444591
TI  - Smoking remains leading cause of premature death in US.

PMID- 24444592
TI  - Statistical decision from k test series with particular focus on population
      genetics tools: a DIY notice.
AB  - In population genetics data analysis, researchers are often faced to the problem
      of decision making from a series of tests of the same null hypothesis. This is
      the case when one wants to test differentiation between pathogens found on
      different host species sampled from different locations (as many tests as number
      of locations). Many procedures are available to date but not all apply to all
      situations. Finding which tests are significant or if the whole series is
      significant, when tests are independent or not do not require the same
      procedures. In this note I describe several procedures, among the simplest and
      easiest to undertake, that should allow decision making in most (if not all)
      situations population geneticists (or biologists) should meet, in particular in
      host-parasite systems. 

PMID- 24444593
TI  - Emergence and evolution of Arsenophonus bacteria as insect-vectored plant
      pathogens.
AB  - Arsenophonus bacteria are among the most biologically diverse and widespread
      endosymbionts of arthropods. Notably, two species, Phlomobacter fragariae and
      Arsenophonus phytopathogenicus, have been characterized as phloem-restricted
      plant pathogens that are obligatorily transmitted by and hosted in planthoppers
      of the family Cixiidae (Hemiptera: Auchenorrhyncha). Here, I review the current
      understanding on the lifestyle transition, evolution, host interaction, and
      infection cycles of these emerging plant pathogens. 

PMID- 24444594
TI  - Isolation of Coxiella burnetii from bovines with history of reproductive
      disorders in India and phylogenetic inference based on the partial sequencing of
      IS1111 element.
AB  - In the present study, a total of 158 blood samples from 148 bovines and 10 dogs
      having a history of reproductive disorders were screened for Coxiella burnetii by
      trans-PCR method. In case of bovines, 6.08% (9/148) blood samples comprised of
      4.54% (4/88) cattle and 8.33% (5/60) buffaloes turned out to be positive for C.
      burnetii DNA while all the samples from dogs (10) were found negative. Of the 9
      PCR-positive bovine blood samples, the organism could be isolated only from 3
      cases of buffaloes by chick embryo inoculation method. Further, to predict the
      homology and genetic diversity, the recovered C. burnetii isolates designated as
      Y1, Y3 and Y7 were partially sequenced for IS1111 gene. On phylogenetic analysis,
      Y3 and Y7 isolates clustered to a common node away from Y1 isolate. This study
      may enlighten the nature of circulating C. burnetii isolates in different parts
      of the world. To the best of our knowledge, this appears to be the first report
      describing phylogenic analysis of C. burnetii isolates based on IS1111 gene
      sequence. 

PMID- 24444595
TI  - Cervical spine involvement early in the course of rheumatoid arthritis.
AB  - OBJECTIVES: Cervical spine involvement in rheumatoid arthritis (RA) is considered
      a feature of long-standing disease. We describe two patients who presented with
      cervical symptoms as early features of RA. METHODS: We report two RA cases with
      cervical spine involvement as early features and use MEDLINE to review the
      literature concerning the frequency and disease duration of this manifestation
      and its imaging with plain radiography, computed tomography (CT), and magnetic
      resonance imaging (MRI). RESULTS: An 80-year-old man with cervical myelopathy
      from a C1-C2 rheumatoid pannus underwent decompression surgery before development
      of peripheral synovitis from RA. A 63-year-old woman presented with neck pain and
      polyarthritis at RA diagnosis, with imaging that confirmed a C1-C2 rheumatoid
      pannus. Onset of cervical spine involvement in RA is generally after 10 years of
      disease duration, ranging from 3 months to 45 years after peripheral synovitis
      among patients with seropositive erosive RA. Occurring in 9-88% of RA patients,
      cervical spine involvement may result in cervical instability due to either
      mechanical compression or vascular impairment of the spinal cord. Bone erosions
      and atlanto-axial subluxation on standard radiographs are two major signs of
      cervical spine involvement in RA. MRI identifies earlier signs of RA and has a
      higher sensitivity in detecting bone erosions compared to conventional
      radiography. CONCLUSIONS: Cervical spine involvement in RA is not an uncommon
      condition but is rare at early disease onset. Symptoms of cervical pain and
      myelopathy should prompt a thorough neurological examination accompanied by
      imaging.

PMID- 24444597
TI  - Rescue intracytoplasmic sperm injection: a systematic review.
AB  - OBJECTIVE: To assess the feasibility, efficacy, and safety of rescue
      intracytoplasmic sperm injection (ICSI) in cases of fertilization failure, using
      a scientific literature search. DESIGN: Systematic review. SETTING: Centers for
      reproductive care. PATIENT(S): Infertility patients with total or partial
      fertilization failure during an IVF cycle. INTERVENTION(S): An electronic
      literature search was performed in PubMed from 1992 through May 2013. The search
      was then expanded by using listed references from selected articles. MAIN OUTCOME
      MEASURE(S): Pregnancy rate. The secondary outcome measures were fertilization
      rate, normal fertilization rate, cleavage rate, birth rate, and malformation
      rate. RESULT(S): Thirty-eight studies including 1,863 patients were included. The
      pooled pregnancy rate was 14.4%; 194 babies were delivered. CONCLUSION(S): Rescue
      ICSI can result in the delivery of a healthy newborn, although the pregnancy
      rates are low. The clinical evidence did not indicate an elevated rate of
      malformations, although the data are limited and incomplete.

PMID- 24444596
TI  - The TWEAK-Fn14 pathway: a potent regulator of skeletal muscle biology in health
      and disease.
AB  - TNF-like weak inducer of apoptosis (TWEAK), a TNF superfamily ligand, and its
      bona fide receptor, the TNF receptor superfamily member fibroblast growth factor
      inducible 14 (Fn14), represent a pivotal axis for shaping both physiological and
      pathological tissue responses to acute or chronic injury and disease. In recent
      years significant advances have been made in delineating the prominent role of
      TWEAK-Fn14 dyad in regulating skeletal muscle mass and metabolism. Also emerging
      from the broad study of tissue injury in skeletal muscle and other organs is the
      role of the TWEAK-Fn14 pathway in promoting fibrosis. This review article
      highlights recent advancements toward understanding how the TWEAK-Fn14 pathway
      regulates the response to various skeletal muscle insults and, more broadly,
      engages multiple mechanisms to drive tissue fibrosis. 

PMID- 24444598
TI  - Digital multiplexed mRNA analysis of functionally important genes in single human
      oocytes and correlation of changes in transcript levels with oocyte protein
      expression.
AB  - OBJECTIVE: To investigate functionally important transcripts in single human
      oocytes with the use of NanoString technology and determine whether observed
      differences are biologically meaningful. DESIGN: Analysis of human oocytes with
      the use of NanoString and immunoblotting. SETTING: University-affiliated
      reproductive medicine unit. PATIENTS: Women undergoing in vitro fertilization.
      INTERVENTION: Human oocytes were analyzed with the use of NanoString or
      immunoblotting. MAIN OUTCOME MEASURES: The abundance of transcripts for ten
      functionally important genes-AURKA, AURKC, BUB1, BUB1B (encoding BubR1), CDK1,
      CHEK1, FYN, MOS, MAP2K1, and WEE2-and six functionally dispensable genes were
      analyzed with the use of NanoString. BubR1 protein levels in oocytes from younger
      and older women were compared with the use of immunoblotting. RESULT(S): All ten
      functional genes but none of the six dispensable genes were detectable with the
      use of NanoString in single oocytes. There was 3- to 5-fold variation in BUB1,
      BUB1B, and CDK1 transcript abundance among individual oocytes from a single
      patient. Transcripts for these three genes-all players within the spindle
      assembly checkpoint surveillance mechanism for preventing aneuploidy-were reduced
      in the same oocyte from an older patient. Mean BUB1B transcripts were reduced by
      1.5-fold with aging and associated with marked reductions in BubR1 protein
      levels. CONCLUSION(S): The abundance of functionally important transcripts
      exhibit marked oocyte-to-oocyte heterogeneity to a degree that is sufficient to
      affect protein expression. Observed variations in transcript abundance are
      therefore likely to be biologically meaningful, especially if multiple genes
      within the same pathway are simultaneously affected.

PMID- 24444599
TI  - Sulfate reduction at low pH to remediate acid mine drainage.
AB  - Industrial activities and the natural oxidation of metallic sulfide-ores produce
      sulfate-rich waters with low pH and high heavy metals content, generally termed
      acid mine drainage (AMD). This is of great environmental concern as some heavy
      metals are highly toxic. Within a number of possibilities, biological treatment
      applying sulfate-reducing bacteria (SRB) is an attractive option to treat AMD and
      to recover metals. The process produces alkalinity, neutralizing the AMD
      simultaneously. The sulfide that is produced reacts with the metal in solution
      and precipitates them as metal sulfides. Here, important factors for
      biotechnological application of SRB such as the inocula, the pH of the process,
      the substrates and the reactor design are discussed. Microbial communities of
      sulfidogenic reactors treating AMD which comprise fermentative-, acetogenic- and
      SRB as well as methanogenic archaea are reviewed.

PMID- 24444600
TI  - Comparison of sealant and infiltrant penetration into pit and fissure caries
      lesions in vitro.
AB  - OBJECTIVES: The aim of this in vitro study was to evaluate the penetration of an
      infiltrant and a sealant, when applied as recommended, into fissure caries
      lesions. METHODS: The fissure systems of extracted human teeth were classified
      according to the international caries detection and assessment system (ICDAS,
      codes: 0, 1, 2). Within each ICDAS-code ten teeth were either etched with 37%
      H3PO4-gel for 60s and subsequently sealed ('Fissure Sealing'; Helioseal; Ivoclar
      Vivadent) or etched with 15% HCl-gel for 120s and subsequently infiltrated
      ('Resin Infiltration'; Icon; DMG). Additionally, ten teeth with ICDAS-code 2 were
      etched with 37% H3PO4-gel for 120s and infiltrated ('Soft-Etch-Infiltration').
      Specimens were cut perpendicular to their surfaces, polished, and confocal
      microscopic images were obtained. Lesion depths (LDmax) and penetration depths
      (PDmax) were measured and percentage penetration was calculated as
      PPmax=PDmax/LDmax*100. RESULTS: Baseline LDmax [median (interquartile range)] for
      ICDAS-code 2 lesions was 1192 (805-1512)MUm. In ICDAS-code 2 lesions PPmax was
      significantly higher for specimens treated with 'Resin Infiltration' [41 (30
      78)%] compared to 'Soft-Etch-Infiltration' [11 (0-21)%] or 'Fissure Sealing' [5
      (0-9)%] (p<0.05; Mann-Whitney test). PPmax did not differ significantly between
      groups in ICDAS-code 0 and 1 lesions (p>0.05). CONCLUSION: The fissure sealant
      when applied after etching with H3PO4-gel only penetrates superficially into non
      cavitated fissure caries lesions. Penetration of an infiltrant is superior in
      particular after etching with HCl-gel. CLINICAL SIGNIFICANCE: Compared with
      sealing, infiltration of fissure caries lesions leads to more deeply infiltrated
      lesions, which might in turn result in superior abilities to hamper caries
      progression.

PMID- 24444601
TI  - Identification of an arylalkylamine N-acyltransferase from Drosophila
      melanogaster that catalyzes the formation of long-chain N-acylserotonins.
AB  - Arylalkylamine N-acyltransferase-like 2(2) (AANATL2) from Drosophila melanogaster
      was expressed and shown to catalyze the formation of long-chain N-acylserotonins
      and N-acydopamines. Subsequent identification of endogenous amounts of N
      acylserotonins and colocalization of these fatty acid amides and AANATL2
      transcripts gives supporting evidence that AANATL2 has a role in the biosynthetic
      formation of these important cell signalling lipids. 

PMID- 24444602
TI  - Attenuation of hydrogen peroxide-mediated oxidative stress by Brassica juncea
      annexin-3 counteracts thiol-specific antioxidant (TSA1) deficiency in
      Saccharomyces cerevisiae.
AB  - Brassica juncea annexin-3 (BjAnn3) was functionally characterized for its ability
      to modulate H2O2-mediated oxidative stress in Saccharomyces cerevisiae. BjAnn3
      showed a significant protective role in cellular-defense against oxidative stress
      and partially alleviated inhibition of mitochondrial respiration in presence of
      exogenously applied H2O2. Heterologous expression of BjAnn3 protected membranes
      from oxidative stress-mediated damage and positively regulated antioxidant gene
      expression for ROS detoxification. We conclude that, BjAnn3 partially counteracts
      the effects of thioredoxin peroxidase 1 (TSA1) deficiency and aids in cellular
      protection across kingdoms. Despite partial compensation of TSA1 by BjAnn3 in
      cell-viability tests, the over-complementation in ROS-related features suggests
      the existence of both redundant (e.g. ROS detoxification) and distinct features
      (e.g. membrane protection versus proximity-based redox regulator) of both
      proteins. 

PMID- 24444603
TI  - Upregulated miR-106a plays an oncogenic role in pancreatic cancer.
AB  - Carcinogenesis is a complex process during which cells undergo genetic and
      epigenetic alterations. MicroRNAs control gene expression by negatively
      regulating protein-coding mRNAs. Several reports demonstrated that miR-106a is up
      regulated in gastric and colorectal cancers and promotes tumor progression. In
      contrast, in glioma miR-106a plays the role of a tumor suppressor gene rather
      than an oncogene. Here we demonstrate that a high level of miR-106a expression is
      present in pancreatic cancer. Furthermore, our investigation shows that miR-106a
      has an oncogenic role in pancreatic tumorigenesis by promoting cancer cell
      proliferation, epithelial-mesenchymal transition and invasion by targeting tissue
      inhibitors of metalloproteinase 2 (TIMP-2). MiR-106a could be a critical
      therapeutic target in pancreatic cancer. 

PMID- 24444604
TI  - A miR-155-dependent microRNA hierarchy in dendritic cell maturation and
      macrophage activation.
AB  - MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many
      cellular pathways. MiRNAs associate with members of the Argonaute protein family
      and bind to partially complementary sequences on mRNAs and induce translational
      repression or mRNA decay. Using deep sequencing and Northern blotting, we
      characterized miRNA expression in wild type and miR-155-deficient dendritic cells
      (DCs) and macrophages. Analysis of different stimuli (LPS, LDL, eLDL, oxLDL)
      reveals a direct influence of miR-155 on the expression levels of other miRNAs.
      For example, miR-455 is negatively regulated in miR-155-deficient cells possibly
      due to inhibition of the transcription factor C/EBPbeta by miR-155. Based on our
      comprehensive data sets, we propose a model of hierarchical miRNA expression
      dominated by miR-155 in DCs and macrophages. 

PMID- 24444605
TI  - A micropatterning approach for imaging dynamic Cx43 trafficking to cell-cell
      borders.
AB  - The precise expression and timely delivery of connexin 43 (Cx43) proteins to form
      gap junctions are essential for electrical coupling of cardiomyocytes. Growing
      evidence supports a cytoskeletal-based trafficking paradigm for Cx43 delivery
      directly to adherens junctions at the intercalated disc. A limitation of Cx43
      localization assays in cultured cells, in which cell-cell contacts are essential,
      is the inability to control for cell geometry or reproducibly generate contact
      points. Here we present a micropatterned cell pairing system well suited for live
      microscopy to examine how the microtubule and actin cytoskeleton confer
      specificity to Cx43 trafficking to precisely defined cell-cell junctions. This
      system can be adapted for other cell types and used to study dynamic
      intracellular movements of other proteins important for cell-cell communication. 

PMID- 24444606
TI  - MiR-98 is involved in rat embryo implantation by targeting Bcl-xl.
AB  - In a previous study, via microRNA microarray analysis we found that miR-98 is
      differentially expressed in rat uteri during the peri-implantation period
      (unpublished data). However, the role of miR-98 in rat embryo implantation
      remains elusive. Here, we found that the level of miR-98 is lower on day 5 and 6
      of gestation (g.d. 5-6) than that on g.d. 3-4 and g.d. 7-8 in rat. MiR-98
      expression is significantly decreased by delayed implantation. Down-regulation of
      miR-98 promotes ESC proliferation and inhibits apoptosis. Up-regulation of miR-98
      displays opposite effects. Further investigation revealed that miR-98 can bind to
      the 3'-untranslated region (3'-UTR) of B-cell lymphoma-extra large (Bcl-xl) to
      inhibit Bcl-xl translation. Collectively, down-regulation of miR-98 in rat uterus
      during the receptive phase is linked to the increase of cell proliferation via
      targeting Bcl-xl. 

PMID- 24444607
TI  - The chaperone FdsC for Rhodobacter capsulatus formate dehydrogenase binds the bis
      molybdopterin guanine dinucleotide cofactor.
AB  - Molybdoenzymes are complex enzymes in which the molybdenum cofactor (Moco) is
      deeply buried in the enzyme. Most molybdoenzymes contain a specific chaperone for
      the insertion of Moco. For the formate dehydrogenase FdsGBA from Rhodobacter
      capsulatus the two chaperones FdsC and FdsD were identified to be essential for
      enzyme activity, but are not a subunit of the mature enzyme. Here, we purified
      and characterized the FdsC protein after heterologous expression in Escherichia
      coli. We were able to copurify FdsC with the bound Moco derivate bis
      molybdopterin guanine dinucleotide. This cofactor successfully was used as a
      source to reconstitute the activity of molybdoenzymes. 

PMID- 24444608
TI  - Expression of TLE3 by bone marrow stromal cells is regulated by canonical Wnt
      signaling.
AB  - Transducing-like enhancer of split 3 (TLE3), one of the Groucho/TLE family
      members, targets Runx2 transcription and suppresses osteoblast differentiation in
      bone marrow stromal cells (BMSCs). Here, we identify Wnt responsive elements of
      the TLE3 promoter region through comparative genomic and functional analyses and
      show that expression of TLE3 is increased by Wnt signaling, which is important
      for osteoblast differentiation. We also demonstrated that TLE3 is able to
      suppress canonical Wnt signaling in BMSCs. Taken together, our data suggest that
      induction of TLE3 by Wnt signaling is part of a negative feedback loop active
      during osteoblast differentiation. 

PMID- 24444609
TI  - Restoration of p53/miR-34a regulatory axis decreases survival advantage and
      ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells.
AB  - Tumor-suppressive miR-34a, a direct target of p53, has been shown to target
      several molecules of cell survival pathways. Here, we show that capsaicin-induced
      oxidative DNA damage culminates in p53 activation to up-regulate expression of
      miR-34a in non-small cell lung carcinoma (NSCLC) cells. Functional analyses
      further indicate that restoration of miR-34a inhibits B cell lymphoma-2 (Bcl-2)
      protein expression to withdraw the survival advantage of these resistant NSCLC
      cells. In such a proapoptotic cellular milieu, where drug resistance proteins are
      also down-regulated, p53-transactivated Bcl-2 associated X protein (Bax) induces
      apoptosis via the mitochondrial death cascade. Our results suggest that p53/miR
      34a regulatory axis might be critical in sensitizing drug-resistant NSCLC cells. 

PMID- 24444610
TI  - The disability burden associated with stroke emerges before stroke onset and
      differentially affects blacks: results from the health and retirement study
      cohort.
AB  - BACKGROUND: Few longitudinal studies compare changes in instrumental activities
      of daily living (IADLs) among stroke-free adults to prospectively document IADL
      changes among adults who experience stroke. We contrast annual declines in IADL
      independence for older individuals who remain stroke free to those for
      individuals who experienced stroke. We also assess whether these patterns differ
      by sex, race, or Southern birthplace. METHODS: Health and Retirement Study
      participants who were stroke free in 1998 (n = 17,741) were followed through 2010
      (average follow-up = 8.9 years) for self- or proxy-reported stroke. We used
      logistic regressions to compare annual changes in odds of self-reported
      independence in six IADLs among those who remained stroke free throughout follow
      up (n = 15,888), those who survived a stroke (n = 1,412), and those who had a
      stroke and did not survive to participate in another interview (n = 442). We
      present models adjusted for demographic and socioeconomic covariates and also
      stratified on sex, race, and Southern birthplace. RESULTS: Compared with similar
      cohort members who remained stroke free, participants who developed stroke had
      faster declines in IADL independence and lower probability of IADL independence
      prior to stroke. After stroke, independence declined at an annual rate similar to
      those who did not have stroke. The black-white disparity in IADL independence
      narrowed poststroke. CONCLUSION: Racial differences in IADL independence are
      apparent long before stroke onset. Poststroke differences in IADL independence
      largely reflect prestroke disparities.

PMID- 24444613
TI  - The impact of individual characteristics in self-esteem and locus of control of
      young adults with visual impairments.
AB  - In this study the impact of personal/individual characteristics (gender, vision
      status, age, age at loss of sight, recency of vision loss, education level,
      employment status, and ability of independent movement) in locus of control (LOC)
      and self-esteem were examined. Eighty-four young adults with visual impairments
      (42 with blindness and 42 with low vision) took part in this study. The
      significant predictors of self-esteem were vision status, age at loss of sight,
      recency of vision loss and educational level. Moreover, significant predictors of
      LOC were vision status and independent movement. 

PMID- 24444611
TI  - Who are the Okinawans? Ancestry, genome diversity, and implications for the
      genetic study of human longevity from a geographically isolated population.
AB  - Isolated populations have advantages for genetic studies of longevity from
      decreased haplotype diversity and long-range linkage disequilibrium. This permits
      smaller sample sizes without loss of power, among other utilities. Little is
      known about the genome of the Okinawans, a potential population isolate,
      recognized for longevity. Therefore, we assessed genetic diversity, structure,
      and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese,
      and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human
      Mapping 500K array. Principal component analysis, haplotype coverage, and linkage
      disequilibrium decay revealed a distinct Okinawan genome-more homogeneity, less
      haplotype diversity, and longer range linkage disequilibrium. Population
      structure and admixture analyses utilizing 52 global reference populations from
      the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered
      almost exclusively with East Asians. Sibling relative risk (lambdas) analysis
      revealed that siblings of Okinawan centenarians have 3.11 times (females) and
      3.77 times (males) more likelihood of centenarianism. These findings suggest that
      Okinawans are genetically distinct and share several characteristics of a
      population isolate, which are prone to develop extreme phenotypes (eg, longevity)
      from genetic drift, natural selection, and population bottlenecks. These data
      support further exploration of genetic influence on longevity in the Okinawans.

PMID- 24444612
TI  - An investigation of the factors affecting flatfoot in children with delayed motor
      development.
AB  - This study investigated the prevalence of flatfoot in children with delayed motor
      development and the relevant factors affecting it. In total, 121 preschool-aged
      children aged 3-6 with delayed motor development (male: 81; female: 40) were
      enrolled in the motor-developmentally delayed children group, and 4 times that
      number, a total of 484 children (male: 324; female: 160), of gender- and age
      matched normal developmental children were used as a control group for further
      analyses. The age was from 3.0 to 6.9 years old for the participants. The
      judgment criterion of flatfoot was the Chippaux-Smirak index >62.70%, in
      footprint measurement. The results showed that the prevalence of flatfoot in
      children with motor developmental delay was higher than that in normal
      developmental children, approximately 58.7%, and that it decreased with age from
      62.8% of 3-year-olds to 50.0% of 6-year-olds. The results also showed that motor
      developmentally delayed children with flatfoot are at about 1.5 times the risk of
      normal developmental children (odds ratio=1.511, p=0.005). In addition, the
      prevalence of flatfoot is relatively higher in overweight children with delayed
      motor development, and that in obese children is even as high as 95.8% (23/24).
      Children with both excessive joint laxity and delayed development are more likely
      to suffer from flatfoot. The findings of this study can serve as a reference for
      clinical workers to deal with foot issues in children with delayed motor
      development. 

PMID- 24444614
TI  - A cytoarchitectonic and TH-immunohistochemistry characterization of the dopamine
      cell groups in the substantia nigra, ventral tegmental area and retrorubral field
      in the rock cavy (Kerodon rupestris).
AB  - The 3-hydroxytyramine/dopamine is a monoamine of the catecholamine group and it
      is a precursor of the noradrenaline and adrenaline synthesis, in which the enzyme
      tyrosine hydroxylase acts as a rate-limiting enzyme. The dopaminergic nuclei
      retrorubral field (A8 group), substantia nigra pars compacta (A9 group) and
      ventral tegmental area (A10 group) are involved in three complex circuitries
      named mesostriatal, mesocortical and mesolimbic, which are directly related to
      various behavioral manifestations such as motor control, reward signaling in
      behavioral learning, motivation and pathological manifestations of Parkinson's
      disease and schizophrenia. The aim of this study was to describe the delimitation
      of A8, A9 and A10 groups and the morphology of their neurons in the brain of the
      rock cavy (Kerodon rupestris), a typical Brazilian Northeast rodent belonging to
      the suborder Hystricomorpha, family Caviidae. Coronal and sagittal sections of
      the rock cavy brains were submitted to Nissl staining and TH
      immunohistochemistry. The organization of these dopaminergic nuclei in the rock
      cavy brain is very similar to that found in other animals of the Rodentia order,
      except for the presence of the tail of the substantia nigra, which is found only
      in the species under study. The results revealed that, apart some morphological
      variations, A8, A9 and A10 groups are phylogenetically stable brain structures. 

PMID- 24444615
TI  - 2014 is finally here--oh my!

PMID- 24444616
TI  - CPT update for 2014.
AB  - Changes this year include revisions to transitional care management codes and new
      interprofessional consultation codes.

PMID- 24444617
TI  - 10 steps to preparing your office for ICD-10--now.

PMID- 24444618
TI  - How to bridge the health literacy gap.
AB  - Communicating with patients in a way they understand will lead to better outcomes
      and avoid mistakes and uncertainty.

PMID- 24444619
TI  - Making sense of meaningful use stage 2: second wave or tsunami?

PMID- 24444627
TI  - Pre-op Eval.
AB  - A review of the medical app Pre-op Eval using the FPM "SPPACES" criteria

PMID- 24444628
TI  - A few moments of lifestyle advice.

PMID- 24444629
TI  - [Strengthen the clinical study on allergic rhinitis].

PMID- 24444630
TI  - [Suggestion on the diagnosis and treatment of vasomotor rhinitis].

PMID- 24444631
TI  - [Development of allergic rhinitis and its impact on asthma: 4-5 year follow-up
      study of preschool children].
AB  - OBJECTIVE: To observe the development of allergic rhinitis (AR) in preschool
      children, and the variation of sensitization to airborne allergens 5 years later,
      also the link between AR and asthma. METHODS: Two hundred and fourty-eight
      children with AR (AR group) and 217 non-AR children (non-AR group) were surveyed
      using a questionnaire and examined by otolaryngologists with skin prick test
      (SPT) between 2006 and 2007. Among them, 63 children were asked to return to
      hospital to participate in a routine ENT examination and SPT for common inhalant
      allergens. All statistical analysis was performed by a professional statistician
      using SPSS 17.0 statistical software. RESULTS: Two hundred and sixteen
      questionnaires were acquired in AR group and 156 questionnaires were acquired in
      non-AR group. (1) The remission of AR occurred in 37.0% (80/216) 5-years later,
      70.0% (56/80) children who had remission of AR symptoms received the correct
      medication; there was only 49.3% (67/136) children who had nonremission of AR
      symptoms received the correct medication, and there was a statistically
      significant difference (chi(2) = 0.114, P = 0.736). (2) Asthma prevalence was
      increased from 12.5% (27/216) to 14.8% (32/216) in AR group children, there was
      no statistically significant difference (chi(2) = -0.491, P = 0.484). The
      prevalence of asthma was increased slightly from 2.6% (4/156) to 3.2% (5/156) in
      no-AR group children, there was no statistically significant difference (chi(2) =
      0.114, P = 0.736). When asthma in AR group children had tendency of remission, AR
      could also be controlled, and there was a statistically significant difference
      (chi(2) = 5.423, P < 0.05). (3) The total number of sensitization allergen
      decreased compared to the originally test. Dermatophagoides farinae was the most
      common allergen in our survey, while in the originally test, Alternaria tenuis
      was the most common allergen. There was age-dependent tendency to sensitize to
      new classes of allergens was present in children with AR, the number of children
      sensitized to fungal was minimum. CONCLUSIONS: Remission of AR in preschool
      children occurred in 37.0% 5 years later. There is a strong relationship between
      childhood AR and childhood asthma. Sensitization to the airborne allergens may
      change with age.

PMID- 24444632
TI  - [Nasal coblation plasma surgery for the treatment of persistent allergic
      rhinitis: an evaluation of short-term outcomes].
AB  - OBJECTIVE: To evaluate the therapeutic effect of nasal coblation plasma surgery
      for the treatment of persistent allergic rhinitis (PAR). METHODS: One hundred
      patients with mite-sensitized moderate to severe PAR who underwent nasal
      coblation plasma surgery (inferior turbinoplasty plus nasal agger ablation) were
      enrolled in this study. There were 68 male and 32 female patients aged 16 to 62
      years (mean, 36.3 years). The visual analogue scale (VAS) for global rhinitis
      symptoms, nasal provocation test (NPT), anterior rhinomanometry, and T&T
      olfactometry were used to assess the short-term outcomes, preoperatively and
      postoperatively at the end of three months after surgical procedure. SPSS19.0
      software was applied for statistical analysis. RESULTS: At three months after
      treatment, the total nasal symptom VAS scores significantly decreased from 7.0 +/
      2.0 to 2.5 +/- 1.5 (X(-) +/- s; t = 18.00, P = 0.0001). All patients were
      allergic to house dust mites with positive NPT before treatment. At three months
      from the coblation intervention, 88.0% of the patients changed from positive NPT
      to negative, while 12.0% remained as positive. There was a significant reduction
      in total nasal resistance, which diminished from 0.772 +/- 0.224 to 0.221 +/-
      0.112 kPa.s.L(-1) after treatment (t = 22.00, P = 0.0001). Preoperative olfactory
      tests showed hyposmia in 31.0% of the patients, with 22 cases for slight and 9
      cases for moderate disorder. Three months after treatment, 13.0% were diagnosed
      as hyposmia, with 7 cases for slight and 6 cases for moderate disorder (chi(2) =
      10.44, P = 0.005). CONCLUSION: Nasal coblation plasma surgery provides favorable
      short-term outcomes in terms of remarkable improvement in nasal symptoms,
      hyperreactivity of nasal mucosa, nasal flow and olfactory function in patients
      with moderate to severe PAR, but long-term effect needed further observation.

PMID- 24444634
TI  - [Transnasal endoscopic anatomy and approaches to the cavernous sinus].
AB  - OBJECTIVE: The goal of the current study is to describe the transnasal endoscopic
      anatomy of the cavernous sinus and to provide the surgical approaches to this
      area. METHODS: Six silicon-injected adult cadaveric heads (12 sides) were
      dissected through endoscopic endonasal approach. The cavernous sinus and adjacent
      structures were exposed; detailed anatomies were demonstrated. High-quality
      pictures were produced. RESULTS: The cavernous sinus had four walls, namely
      medial, lateral, posterior and superior walls. Five venous spaces within the
      sinus were identified by their relation to the carotid artery; those were the
      medial, lateral, posterosuperior, posteroinferior and anterolateral compartments.
      Three branches arising from the cavernous segment of internal carotid artery from
      proximal to distal were meningohypophyseal trunk, inferolateral trunk and
      McConnell capsular artery. Cavernous sinuses communicated each other by
      intercavernous sinuses, as well as basilar sinus in middle line, and connected
      with superior and inferior petrosal sinuses. The third and fourth nerves coursed
      in superior part of the lateral wall of the cavernous sinus; Meckel's cave
      located in the posteroinferior part of the lateral wall of the cavernous sinus;
      V1 sloped to the superior orbital fissure along the lateral wall; the sixth nerve
      entered the posteroinferior compartment then passed through the internal carotid
      artery and reached to superior orbital fissure. The approaches to the cavernous
      sinus included trans-sphenoid-sellar-medial cavernous sinus (medial to the
      internal carotid artery) and trans-ethmoid-pterygoid-sphenoid-lateral cavernous
      sinus (lateral to the internal carotid artery). Trans-sphenoid-sellar-medial
      cavernous sinus approach was able to expose medial compartment and
      posterosuperior compartment and part of posteroinferior compartment. Trans
      ethmoid-pterygoid-sphenoid-lateral cavernous sinus approach was able to expose
      anteroinferior compartment, lateral cavernous sinus and cranial nerves in lateral
      wall. CONCLUSION: An understanding of the complex relationships of the cavernous
      segment of internal carotid artery and cranial nerves in cavernous sinus is
      paramount for surgically dealing with the disease involved cavernous sinus and
      adjacent region.

PMID- 24444633
TI  - [CT and MRI diagnosis of lesions in unilateral maxillary sinus].
AB  - OBJECTIVE: To study the CT and MRI findings of lesions in unilateral maxillary
      sinus, and to compare the effect of CT and MRI in the differential diagnosis of
      lesions in unilateral maxillary sinus. METHODS: Retrospective analysis of CT and
      contract-enhanced MRI imaging data from 34 patients with lesions in unilateral
      maxillary sinus which were diagnosed by endoscopic sinus surgery and
      postoperative pathology. The CT and contract-enhanced MRI's value in the
      differential diagnosis in lesions in unilateral maxillary sinus was analysed.
      RESULTS: All 34 patients had unilateral maxillary sinus lesions. On CT: soft
      tissue density shadow in the unilateral maxillary sinus was found in all 34
      cases. Five cases showed spot high density with thickening bone in the maxillary
      sinus wall. Eleven cases showed expansion of the opening of maxillary sinuses.
      Two cases showed broken lateral wall of nasal cavity . One case showed soft
      tissue density shadow in the maxillary sinus with curve edge with high density
      shadow which had a tooth shadow in it. Other 14 cases showed only soft density
      shadow in the maxillary sinuses. On MRI: all 34 cases revealed lower signals on
      T1WI compared to gray matter. Little loss signal were found in the inner of the
      maxillary sinus fungal balls on T1WI. Enhanced MR imaging showed no enhanced in
      nasal sinusitis, sinus cysts and polyp of posterior naris. In homogenous
      enhancing and "the cerebral convolution sign" were found in the hemorrhagic and
      necrotic nasal polyp, the nasal inverted papilloma and the malignant tumor cases.
      Higher signals were seen in the nasal sinusitis, fungal balls and the polyp of
      posterior naris cases on T2WI. In homogenous signal with different levels were
      found in the hemorrhagic and necrotic nasal polyp, the nasal inverted papilloma
      and the malignant tumor cases on T2WI. CONCLUSIONS: CT and MRI examination are
      important in the diagnosis of the unilateral maxillary sinus lesions. Both CT and
      MRI had more differential diagnostic value in the unilateral maxillary sinus
      lesions than only CT used.

PMID- 24444635
TI  - [A normative study of auditory development in Mandarin-speaking infants].
AB  - OBJECTIVE: The aim of this study is to investigate the development of auditory
      skills in Mandarin-speaking infants with normal hearing using IT-MAIS, set up
      normal comparison data for evaluating the auditory performance of children with
      hearing loss and provide a basis for establishing an appropriate hearing and
      speech rehabilitation program for them. METHODS: A total of 183 infants with
      Mandarin-speaking patents participated in this investigation which was conducted
      in Beijing, China. 160 infants aged from 1 to 36 months were finally included,
      whose hearing were considered normal according to the history collection, high
      risk registers for hearing loss and hearing screening using DPOAE. All infants
      were divided into 8 groups with 20 infants in each group by their ages. They were
      1 month, 2-3 months, 4-6 months, 7-9 months, 10-12 months, 13-18 months, 19-24
      months and 25-36 months group. The IT-MAIS/MAIS were administered to evaluate
      their development of auditory skills. All statistical analyses were executed
      using the MATLAB R2010a. RESULTS: The detection scores improved with age and
      reached ceiling at 19 months in infants with normal hearing, the regression
      function for prediction of scores from age was score = 0.26*ln(age) + 0.23 and
      prediction of age from score was age = e([score-0.23])/0.26, r(2) = 0.93. The
      recognition scores also increased with age and reached ceiling at 24 months in
      infants with normal hearing, the regression function for prediction of scores
      from age was score = 0.26*ln(age)-0.07 and prediction of age from score was age =
      e([score+0.07])/0.34, r(2) = 0.93. The overall scores which combine the above two
      aspects augmented with age and reached ceiling at 22 months. The regression
      function for prediction of scores from age was score = 0.3*ln(age)+0.09 and
      prediction of age from score was age = e([score-0.09])/0.3, r(2) = 0.95.
      CONCLUSIONS: Auditory skills showed a growth trend with age in infants with
      normal hearing. Scores of different auditory skills can be predicted according to
      their age. Age can also be predicted according to their scores of different
      auditory skills.

PMID- 24444636
TI  - [Endolymphatic sac tumor with von Hippel-Lindau disease: report of two cases with
      testing of von Hippel-Lindau gene].
AB  - OBJECTIVE: Endolymphatic sac tumors (ELSTs) are rare in the general population
      with much higher prevalence in von Hippel-Lindau(VHL) disease. The purpose of
      this study is to present two cases of endolymphatic sac tumor with VHL disease
      with analysis of VHL gene and to explore their association with VHL disease using
      molecular analysis. METHODS: Clinical data of these two patients from different
      VHL families were studied. DNAs extracted from peripheral bloods were amplified
      by the polymerase chain reaction using oligonucleotide primers corresponding to
      the VHL gene, then compared the mutations with the Human Gene Mutation Database.
      RESULTS: In case 1, 6 family members were enrolled in the study. Among them,
      three had been identified to have a germline missense point mutation at codon 194
      of the VHL gene exon 1 (p.S65W). The little sister of the patient (case 1)
      underwent vitrectomy for retinal hemangioblastoma 5 years ago in another
      hospital. The mother of the patient (case 1) was further diagnosed to have a
      cerebellar hemangioblastoma and renal carcinoma in the following physical
      examination. Case 2 with her parents were also tested. Codon 499 of the VHL gene
      exon 3 (p.R167W) were detected in case 2 and her mother, but the mother refused
      further examination. CONCLUSIONS: The genetic diagnosis plays an important role
      in early detection of symptomatic patients and suspected patients. Clinical
      screening for members of the VHL families, and close follow-up of carriers allow
      an early detection of tumors and the metastasis, which is the most common cause
      of death of these patients.

PMID- 24444637
TI  - [Hemi-pharyngolaryngectomy and laryngeal reconstruction with free flaps in T3 and
      T4 hypopharyngeal cancer].
AB  - OBJECTIVE: Resection of local advanced hypopharyngeal cancer often results in
      laryngeal preservation impossible. Free flaps were used to reconstruct and to
      preserve functional larynx. METHODS: Retrospective review of 11 patients who
      underwent resections of extended squamous cell carcinoma of hypopharynx from
      September 2005 to September 2011. Of 11 patients, 5 had T3 lesions and 6 had T4
      lesions; 2 underwent radiotherapy before surgery and other 9 had postoperative
      radiotherapy (60 Gy). A total of 12 free flaps, including 10 radial forearm flaps
      and 2 anterolateral thigh flaps, was used in the 11 patients for laryngo
      pharyngeal reconstruction. RESULTS: The 3 year over all survival rate and disease
      specific survival rate were 43.6% and 48.0%, respectively. The incidence of
      surgical complications was 72.7%, including 1 with carotid blow-up, 2 flap
      failure, 3 fistula, and 1 stenosis. The rate of decannulation was 72.7%, 90.9%
      patients were with oral feeding and 81.8% patients achieved reasonable speech.
      CONCLUSION: Free flaps can be used to reconstruct a functional larynx in local
      advanced hypopharyngeal carcinoma, ensuring a better quality of life for
      patients.

PMID- 24444638
TI  - [Surgical treatment of advanced laryngeal cancer with preservation of laryngeal
      function].
AB  - OBJECTIVE: To explore the surgical methods for advanced laryngeal cancer and long
      term effects of laryngectomy. METHODS: Two hundred and thirty-eight cases of
      laryngeal cancer at different stages, including 103 cases with supraglottic
      cancer, 118 cases with glottic cancer, 3 cases with subglottic cancer, and 14
      cases with recurrent cancer, underwent different kinds of operation from 2000 to
      2010. The TNM classifications were as follows: T3 168 cases, T4 70 cases. Stage
      III 145 cases, Stage IV 93 cases. N0 134 cases,N1 64 cases,N2 38 cases, and N3 2
      cases. The effects of operation, especially with the preservation of laryngeal
      function, was analyzed. The disease-free survival rate was calculated by Kaplan
      Meier methods. RESULTS: Partial laryngectomy was performed on 142 of the 238
      cases (59.7%). Total laryngectomy was performed on 96 cases. In 142 patients who
      received partial laryngectomy with preservation of laryngeal function, the
      trachea cannula was extracted in 90 patients, with the decannulation rate as
      63.4%. The nasal feeding tube was removed and peroral feeding was recovered in
      all patients. The patients undergoing partial laryngectomy succeeded in
      phonation. The 3 years and 5 years disease-free survival rates in all patients
      were 81.4% and 59.5%. The 3 years and 5 years disease-free survival rate of
      partial laryngectomy were 82.9% and 64.3%. The 3 years and 5 years disease-free
      survival rates in total laryngectomy were 79.2% and 52.4%. There was no
      significantly different between the two groups (chi(2) = 2.478, P = 0.115).
      CONCLUSION: For the advanced laryngeal cancer, it is possible to preserve the
      laryngeal function without compromising the remote survival rate by detailed pre
      operational estimation, properly selected operation and skilled surgical
      practice.

PMID- 24444639
TI  - [Imaging and clinical features of nasopharyngeal adenoid cystic carcinoma].
AB  - OBJECTIVE: To analyze the spreading patterns nasopharyngeal carcinoma and
      nasopharyngeal adenoid cystic carcinoma. METHODS: Eighteen pathologically
      confirmed consecutive cases of adenoid cystic carcinomas (ACC) and 182 cases of
      untreated nasopharyngeal carcinomas (NPC) were reviewed. RESULTS: Compared with
      NPC, ACC had higher rates of T4 disease (14.3% vs 38.9%,chi(2) = 7.197, P =
      0.007) and paralyzed cranial nerve (6.0% vs 38.9%,chi(2) = 37.936, P < 0.001) .
      There was no significant difference in skull base invasion rates between 2 groups
      (53.3% vs 66.7%,chi(2) = 1.181, P = 0.277) . ACC had higher rates of MRI-detected
      cranial nerve canal invasion (32.4% vs 55.6%,chi(2) = 3.881, P = 0.049) and
      cavernous sinus invasion (13.7% vs 33.3%,chi(2) = 7.710, P = 0.028) than NPC.
      Lymph node metastasis occurred in 64.8% of ACC, and 11.1% of NPC (chi(2) =
      19.699, P < 0.001) . CONCLUSION: ACC has a higher rate of cranial nerve invasion
      and NPC has a higher rate of lymphatic metastasis.

PMID- 24444640
TI  - [Fine-needle aspiration with measurement of parathyroid hormone levels in
      thyroidectomy].
AB  - OBJECTIVE: Hypoparathyroidism is one of the most serious complications of
      thyroidectomy. It is important to identify the parathyroid glands during
      thyroidectomy. In order to find an economic, simple and less traumatic way to
      identify the parathyroid glands and testify its feasibility, fine-needle
      aspiration of suspected parathyroid tissue was used to measure the parathyroid
      hormone (PTH) levels during the surgical procedure. METHODS: From Nov. 2011 to
      Apr. 2012, 50 patients were recruited for thyroid surgery in the Sun Yat-sen
      University Cancer Centre. During surgery, fine-needle aspiration of suspected
      tissues, including parathyroid gland, thyroid gland, muscle, fat tissue, and
      lymph node, was performed, the PTH levels were measured. In addition, the tissues
      above-mentioned were taken to pathological examination. Statistical processing
      was adopted to determine the sensitivity and specificity of intraoperative fine
      needle aspiration with measurement of PTH level in finding the pathology of the
      parathyroid gland. RESULTS: There were 237 tissues from 50 patients in total, and
      45 of them were certified as the parathyroid glands by pathology. Intra-operative
      PTH (ioPTH) of the tissues in forty-four cases were higher than 600 ng/L, ioPTH
      of the tissues in one case was lower than 600 ng/L, and it was 160 ng/L. The
      highest ioPTH in other cases was 537.7 ng/L. The sensitivity was 97.8%. The
      specificity was 100%. The difference between the sensitivity and the specificity
      of two groups was not statistically significant, and P > 0.05. The level of PTH
      of parathyroid gland were much higher than other tissues, and P < 0.001.
      CONCLUSIONS: The level of ioPTH of parathyroid gland were far higher than
      thyroid, muscle, fat, lymph node. It is an economic, fast and less traumatic way
      to identify the parathyroid gland by using the fine-needle aspiration of the
      parathyroid tissue with measurement of PTH levels. The sensitivity and the
      specificity are high. It can be used in the thyroidectomy to identify the
      parathyroid glands.

PMID- 24444641
TI  - [Endoscope-assisted styloidectomy via postauricular incision].
AB  - OBJECTIVE: To investigate the feasibility of the endoscope-assisted
      styloidectomy. METHODS: Sixty patients with Eagle's syndrome undergoing the
      endoscope-assisted styloidectomy via postauricular incision, including 7
      unilateral and 53 bilateral, between June 2010 and March 2013 were reviewed.
      RESULTS: The styloid processes in all patients were resected successfully via
      this approach, with the incision length range of 2.0 to 2.5 cm. The mean
      operative time was (21.3 +/- 4.8) min(X(-) +/- s), for unilateral surgery and
      (48.5 +/- 11.4) min for bilateral surgery. Fifty-four patients symptom showed
      complete remission of symptom, 3 cases with decrease in symptom and other 3 cases
      with no significant relief of symptom after surgery. None case recurred for
      follow-up of 3 to 70 months. There were 3 sides with ear numbness after surgery
      for 3 months, and one case had transient facial paralysis and recovered after 3
      months. CONCLUSIONS: The endoscope-assisted styloidectomy via postauricular
      incision is effective and feasible.

PMID- 24444642
TI  - [Adenovirus-mediated interleukin-24 enhanced the antitumor effect of radiotherapy
      on nasopharyngeal carcinoma in vitro and in vivo].
AB  - OBJECTIVE: To investigate the inhibitory effect of adenovirus-mediated
      interleukin-24 (AdVIL-24) in conjunction with ionizing radiation on the growth of
      CNE-2Z human NPC cells in vitro and in vivo and underlying mechanisms. METHODS:
      The CNE-2Z cells were transfected with AdVIL-24 alone or combined with
      radiotherapy. The transfection efficacy of AdVIL-24 in CNE-2Z cells was
      determined by RT-PCR and Western blot. Cell growth was assessed by MTT assay,
      apoptosis was detected by flow cytometry through double staining of cells with
      propidium iodide (PI) and the expressions of P21, P27, cyclin E, CDK2, Bax, Bcl-2
      and caspase-3 were detected with semi-quantitative RT-PCR and western blot,
      respectively. Anti-tumor effect of AdVIL-24 was observed using CNE-2Z human
      nasopharyngeal carcinoma transplanted tumor in athymic nude mouse model. The
      volume and weight of the xenografted tumors were measured and the expressions of
      P21, P27, cyclin E, CDK2, Bax, Bcl-2, caspase-3, CD34 and VEGF and the
      microvessel density in xenografted tumors were determined by immunohistochemistry
      analysis. RESULTS: AdVIL-24 plus radiotherapy induced cell growth inhibition (P <
      0.05, Q3d, 4d = 0.916, 1.050) , cell cycle G1 phase arrest(50.37%, P < 0.05, Q =
      1.042) and apoptosis (48.82%, P < 0.05, Q = 1.042) , substantial up regulations
      of P21, P27, the ratio of Bax/Bcl-2 and cleaved caspase-3 and down regulations of
      cyclin E and CDK2 (P < 0.05, QP21 = 0.959, QP27 = 0.956, Qcyclin E = 1.078, QCDK2
      = 1.046, QBax/Bcl-2 = 0.995) in vitro. In the xenografted tumors, AdVIL-24 plus
      radiotherapy induced cell growth inhibition (P < 0.05, Qvolume14 = 1.053, Qweight
      = 1.004) , apoptosis (P < 0.05, Q = 0.974) , substantial upregulation of P21,
      P27, the ratio of Bax/Bcl-2 and cleaved caspase-3 and downregulation of cyclin E
      and CDK2 (P < 0.05; QP21 = 0.920, QP27 = 0.937, QcyclinE = 1.060, QCDK2 = 1.019,
      QBax/Bcl-2 = 0.982, Qcleaved-Caspase-3 = 0.927) , decreased the tumor vessel CD34
      expression and microvessel density. AdVIL-24 potentially blocked the radiation
      induced enhancement of VEGF. CONCLUSION: AdVIL-24 gene therapy combined with
      radiotherapy may be a novel and effective treatment strategy for human NPC.

PMID- 24444643
TI  - [A case of endotracheal recurrence of columnar cell variant of papillary thyroid
      carcinoma after surgery].

PMID- 24444644
TI  - [A case of nasopharyngeal Castleman disease].

PMID- 24444645
TI  - [Hypoglossal nerve paraganglioma:report of a case].

PMID- 24444646
TI  - [Minutes of the 2013 China rhinology annual meeting].

PMID- 24444647
TI  - [Mitochondrial dysfunction and auditory neuropathy].

PMID- 24444648
TI  - [Interpretation of American 2011 clinical practice guidelines for pediatric
      tonsillectomy].

PMID- 24444649
TI  - Exchange narrowing of the phonon contribution to the electron spin resonance line
      width in exchange-coupled magnetic insulators.
AB  - In this paper we extend earlier calculations of the phonon contribution to the
      electron spin resonance line width at high temperatures in exchange-coupled
      magnetic insulators. We show that the one-phonon contribution is exchange
      narrowed, similar to the static anisotropy contribution. The effect of the
      exchange narrowing is to limit contributing phonons to those modes whose energies
      are less than a cutoff, gamma(max), that is proportional to the exchange
      interaction. Linear-T behavior in the line width occurs when kBT is greater than
      gamma(max). 

PMID- 24444650
TI  - Improvement of anticoagulant treatment using a dynamic decision support
      algorithm: a Danish Cohort study.
AB  - INTRODUCTION: Warfarin is the most widely prescribed vitamin K antagonist and in
      the United States and Europe more than 10 million people are currently in long
      term oral anticoagulant treatment. This study aims to retrospectively validate a
      dynamic statistical model providing dosage suggestions to patients in warfarin
      treatment. MATERIALS AND METHODS: The model was validated on a cohort of 553
      patients with a mean TTR of 83%. Patients in the cohort were self-monitoring and
      managed by a highly specialised anticoagulation clinic. The predictive model
      essentially consists of three parts handling INR history, warfarin dosage and
      biological noise, which allows for prediction of future INR values and optimal
      warfarin dose to stay on INR target. Further, the model is based on parameters
      initially being set to population values and gradually individualised during
      monitoring of patients. PRIMARY OUTCOME: Time in therapeutic range was used as
      surrogate quality measure of the treatment, and model-suggested dosage of
      warfarin was used to assess the accuracy of the model performance. RESULTS: The
      accuracy of the model predictions measured as median absolute error was 0.53
      mg/day (interquartile range from 0.25 to 1.0). The model performance was
      evaluated by the difference between observed and predicted warfarin intake in the
      preceding week of an INR measurement. In more than 70% of the cases where INR
      measurements were outside the therapeutic range, the model suggested a more
      reasonable dose than the observed intake. CONCLUSION: Applying the proposed
      dosing algorithm can potentially further increase the time in INR target range
      beyond 83%.

PMID- 24444651
TI  - Description of an outbreak of human trichinellosis in an area of Argentina
      historically regarded as Trichinella-free: the importance of surveillance
      studies.
AB  - Trichinellosis is an important food-borne zoonosis which is not treated as a
      major public health concern in Argentina. After more than 20 years without
      reports of infection in an area regarded as Trichinella-free, research studies
      reported that infection occurred in humans, pigs and game animals, including the
      recent outbreak of human trichinellosis revealed here. The outbreak, affecting 64
      individuals, occurred in July 2010 in the province of Entre Rios. Epidemiological
      studies, clinical observations, laboratory analyses and immunoserological
      specific assays (indirect immunofluorescence, IIF, and ELISA) were performed.
      Food samples were analyzed by artificial digestion, and Trichinella larvae
      isolates were identified to the species level by multiplex PCR. The main source
      of infection, commercially available food, had a parasite load of 1.1 muscle
      larvae per gram. Larvae were identified as Trichinella spiralis. Patients
      presented predominantly with oedema, fever and myalgia; and laboratory findings
      and/or immunoserological tests were positive for trichinellosis. Individuals
      received outpatient treatment. No deaths or secondary sequelae were recorded.
      Results suggest that the presence of T. spiralis infection should be suspected in
      all endemic areas, especially where animal husbandry and official food safety
      controls are not properly conducted. The lack of the cases reported ought not to
      be taken as a proof of parasite absence. We highlight the importance of the
      urgent need to implement interdisciplinary and inter-institutional programs aimed
      to control infection transmission, to guarantee food safety and to conduct
      epidemiological surveillance studies. 

PMID- 24444652
TI  - Center of pressure velocity reflects body acceleration rather than body velocity
      during quiet standing.
AB  - The purpose of this study was to test the hypothesis that the center of pressure
      (COP) velocity reflects the center of mass (COM) acceleration due to a large
      derivative gain in the neural control system during quiet standing. Twenty-seven
      young (27.2+/-4.5 years) and twenty-three elderly (66.2+/-5.0 years) subjects
      participated in this study. Each subject was requested to stand quietly on a
      force plate for five trials, each 90 s long. The COP and COM displacements, the
      COP and COM velocities, and the COM acceleration were acquired via a force plate
      and a laser displacement sensor. The amount of fluctuation of each variable was
      quantified using the root mean square. Following the experimental study, a
      simulation study was executed to investigate the experimental findings. The
      experimental results revealed that the COP velocity was correlated with the COM
      velocity, but more highly correlated with the COM acceleration. The equation of
      motion of the inverted pendulum model, however, accounts only for the correlation
      between the COP and COM velocities. These experimental results can be
      meaningfully explained by the simulation study, which indicated that the neural
      motor command presumably contains a significant portion that is proportional to
      body velocity. In conclusion, the COP velocity fluctuation reflects the COM
      acceleration fluctuation rather than the COM velocity fluctuation, implying that
      the neural motor command controlling quiet standing posture contains a
      significant portion that is proportional to body velocity.

PMID- 24444653
TI  - Can we unmask features of spasticity during gait in children with cerebral palsy
      by increasing their walking velocity?
AB  - BACKGROUND AND AIM: Spasticity is a velocity dependent feature present in most
      patients with cerebral palsy (CP). It is commonly measured in a passive
      condition. The aim of this study was to highlight markers of spasticity of
      gastrocnemius and hamstring muscles during gait by comparing the effect of
      increased walking velocity of CP and typical developing (TD) children. METHODS:
      53 children with spastic CP and 17 TD children were instructed to walk at self
      selected speed, faster and as fast as possible without running. Kinematics,
      kinetics and electromyography (EMG) were collected and muscle length and muscle
      lengthening velocity (MLV) were calculated. To compare the data of both groups, a
      linear regression model was created which resulted in two non-dimensional gait
      velocities. A difference score (DS) was calculated between the high and low
      velocity values for both groups. RESULTS: 103 gait parameters were analyzed of
      which 16 had a statistically significant DS between TD and CP groups. The spastic
      gastrocnemius muscle presented at high velocity with a higher ankle angular
      velocity, plantar flexion moment, power absorption and increased EMG signal
      during loading response. The spastic hamstrings demonstrated at high velocity a
      delayed maximum knee extension moment at mid-stance and increasing hip extension
      moment and hip power generation. The hamstrings also presented with a lower MLV
      during swing phase. CONCLUSIONS: A limited number of gait parameters differ
      between CP and TD children when increasing walking velocity, giving indirect
      insight on the effect of spasticity on gait.

PMID- 24444655
TI  - VAP incidence in cardiac arrest survivors treated with TH and SDD: our
      experience.

PMID- 24444654
TI  - Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a
      family history of cancer.
AB  - We studied 2332 individuals with monoallelic mutations in MUTYH among 9504
      relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We
      estimated CRC risks through 70 years of age of 7.2% for male carriers of
      monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for
      female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of
      family history. For monoallelic MUTYH mutation carriers with a first-degree
      relative with CRC diagnosed by 50 years of age who does not have the MUTYH
      mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women
      (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH
      with a first-degree relative with CRC are sufficiently high to warrant more
      intensive screening than for the general population.

PMID- 24444657
TI  - The impact of Wii Fit intervention on dynamic balance control in children with
      probable Developmental Coordination Disorder and balance problems.
AB  - The aim of this study was to examine differences in the performance of children
      with probable Developmental Coordination Disorder (p-DCD) and balance problems
      (BP) and typical developing children (TD) on a Wii Fit task and to measure the
      effect on balance skills after a Wii Fit intervention. Twenty-eight children with
      BP and 20 TD-children participated in the study. Motor performance was assessed
      with the Movement Assessment Battery for Children (MABC2), three subtests of the
      Bruininks Oseretsky Test (BOT2): Bilateral Coordination, Balance and Running
      Speed & Agility, and a Wii Fit ski slalom test. The TD children and half of the
      children in the BP group were tested before and after a 6weeks non-intervention
      period. All children with BP received 6weeks of Wii Fit intervention (with games
      other than the ski game) and were tested before and afterwards. Children with BP
      were less proficient than TD children in playing the Wii Fit ski slalom game.
      Training with the Wii Fit improved their motor performance. The improvement was
      significantly larger after intervention than after a period of non-intervention.
      Therefore the change cannot solely be attributed to spontaneous development or
      test-retest effect. Nearly all children enjoyed participation during the 6weeks
      of intervention. Our study shows that Wii Fit intervention is effective and is
      potentially a method to support treatment of (dynamic) balance control problems
      in children. 

PMID- 24444656
TI  - Prevention of BMS-777607-induced polyploidy/senescence by mTOR inhibitor AZD8055
      sensitizes breast cancer cells to cytotoxic chemotherapeutics.
AB  - Targeted inhibition of MET/RON signaling by tyrosine kinase inhibitor BMS-777607
      for cancer treatment is currently under clinical trials. We have previously shown
      that BMS-777607 induces chemoresistance in vitro by causing polyploidy, which
      hampers therapeutic efficacy. Here, we studied polyploidy-associated senescence
      induced by BMS-777607 in breast cancer cells and its prevention by mTOR inhibitor
      AZD8055, leading to increased chemosensitivity. In breast cancer T-47D and ZR-75
      1 cells, BMS-777607 induced phenotypic changes including enlarged cellular size,
      flattened morphology, increased DNA content, and activity of senescence
      associated beta-galactosidase. These changes were accompanied by increased
      p21/WAF1 expression and decreased Retinoblastoma Ser(780) phosphorylation,
      indicating that BMS-777607 induces not only polyploidy but also senescence. The
      appearance of senescence was associated with polyploidy in which beta
      galactosidase is exclusively expressed in polyploid cells. Survivin expression
      was increased in polyploid/senescent cells as analyzed by Western blotting.
      Increased survivin accumulated both in the nucleus and cytoplasm and dissociated
      with condensed DNA and mitotic spindle at the metaphase. Abnormal accumulation of
      survivin also rendered polyploid/senescent cells insensitive to cytotoxic
      activities of YM155, a DNA damaging agent with a suppressive effect on survivin
      gene transcription. AZD8055, a specific mTOR inhibitor, effectively prevented BMS
      777607-induced polyploidy and senescence and restored survivin expression and its
      nuclear localization to normal levels. Although a synergism was not observed, BMS
      777607 plus AZD8055 increased cancer cell sensitivity toward different cytotoxic
      chemotherapeutics. In conclusion, BMS-777607-induced chemoresistance is
      associated with cell polyploidy and senescence. Inhibition of mTOR signaling by
      AZD8055 prevents BMS-777607-induced polyploidy/senescence and increases breast
      cancer cell chemosensitivity.

PMID- 24444658
TI  - Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for
      hepatitis C virus genotype 1 null responders.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection and
      prior null response (<2 log HCV RNA decline after ? 12 weeks of PegIFN/RBV) have
      limited options. We evaluated daclatasvir plus once- or twice-daily asunaprevir
      in non-cirrhotic genotype 1 null responders. METHODS: In this randomized, phase
      2a, open-label, 24-week treatment study, 101 patients received daclatasvir (60
      mg) once-daily. In addition, 38 genotype 1b patients received asunaprevir (200mg)
      twice- (DUAL A1) or once-daily (DUAL A2); 36 genotype 1a and 5 genotype 1b
      patients received asunaprevir twice- (QUAD B1) or once-daily (QUAD B2) plus
      PegIFN/RBV; and 18 genotype 1a and 4 genotype 1b patients received asunaprevir
      twice-daily plus ribavirin (TRIPLE B3). The primary endpoint was undetectable HCV
      RNA 12 weeks post-treatment (sustained virologic response, SVR12). RESULTS:
      Across all groups, mean HCV RNA was ? 6 log IU/ml, and 99% of patients had a non
      CC IL28B genotype. SVR12 rates were 78% (A1), 65% (A2), 95% (B1), and 95% (B2).
      In B3, most genotype 1a patients experienced virologic breakthrough. The most
      common adverse events were headache, diarrhea, and asthenia. Grade 3-4
      aminotransferase elevations were infrequent and not treatment-limiting.
      CONCLUSIONS: In genotype 1 null responders, daclatasvir plus twice-daily
      asunaprevir DUAL therapy is effective for most genotype 1b patients, and
      daclatasvir, asunaprevir, and PegIFN/RBV QUAD therapy is effective for nearly all
      genotype 1a and 1b patients; but neither DUAL nor TRIPLE therapy is effective for
      genotype 1a patients. Interferon-free regimens including daclatasvir and twice
      daily asunaprevir for genotype 1 null responders should be tailored to subtype.

PMID- 24444661
TI  - Intraoperative prophylactic and therapeutic non-invasive ventilation: a
      systematic review.
AB  - Non-invasive ventilation (NIV) has been used to prevent or to treat perioperative
      acute respiratory failure (ARF). Intraoperative prophylactic and therapeutic use
      of NIV could be of interest to patients with anticipated difficulty in
      postoperative weaning from mechanical ventilation or to patients refusing
      tracheal intubation. Intraoperative NIV might also be useful when deep sedation
      is required, as this can cause respiratory depression. PubMed, Embase, Google
      Scholar, and Cochrane Library were searched for pertinent studies. Inclusion
      criteria were NIV use during surgery and adult patients; the exclusion criteria
      were NIV application only in the preoperative or postoperative periods,
      paediatric patients, NIV applied as negative pressure ventilation. Thirty papers
      including 618 patients were included for final analysis. Intraoperative
      therapeutic NIV to treat ARF was reported for 92 patients and in all those cases,
      including six Caesarean sections, surgery was completed uneventfully.
      Intraoperative prophylactic NIV to avoid ARF was described in 24 patients with
      severe respiratory limitation and in 502 healthy patients during deep sedation.
      Three patients could not be successfully ventilated due to upper airway
      obstruction, but no further complication was reported. Intraoperative NIV appears
      feasible, safe, and potentially useful, particularly when tracheal intubation is
      best avoided. However, high-quality, randomized studies are required. 

PMID- 24444660
TI  - Advanced cardiac amyloidosis associated with normal interventricular septal
      thickness: an uncommon presentation of infiltrative cardiomyopathy.
AB  - BACKGROUND: Increased interventricular septal (IVS) thickness on echocardiography
      is a diagnostic criterion for cardiac amyloidosis and classically precedes
      decrement in left ventricular ejection fraction (LVEF). The investigators
      describe patients with histologically confirmed cardiac amyloidosis who had
      significant myocardial dysfunction (LVEF <= 40%) despite having normal IVS
      thickness. METHODS: All patients with systemic amyloidosis and LVEFs <= 40% were
      analyzed to identify the prevalence of normal IVS thickness. Patients with known
      histories of cardiomyopathy or coronary artery disease were excluded. Histologic
      evaluation of tissue included assessment of amyloid burden and average myocyte
      diameter. RESULTS: There were 255 patients with amyloidosis with LVEFs <= 40%, of
      whom seven (3%) had normal IVS thickness and histologic confirmation of cardiac
      involvement. Of these, six had immunoglobulin light chain amyloidosis, and one
      had senile amyloidosis. A majority of patients (86%) presented with new-onset
      cardiac dysfunction associated with edema and/or dyspnea. Electrocardiographic
      findings included low voltage (43%) and a pseudoinfarct pattern (29%). The 1-year
      survival from initial tissue diagnosis in the cohort with normal IVS thickness
      was similar to matched patients with amyloidosis with increased IVS thickness and
      LVEF <= 40% (21% vs 18%, respectively, P = .32). Myocardial tissue amyloid burden
      and average myocyte diameter were significantly reduced in cases compared with
      controls. CONCLUSIONS: Cardiac amyloidosis can uncommonly present with normal IVS
      thickness despite significant myocardial dysfunction. The prognosis of these
      patients is as poor as those with increased IVS thickness. Amyloidosis should be
      considered in the differential diagnosis of patients with cardiomyopathy and
      reduced LVEFs despite normal IVS thickness.

PMID- 24444659
TI  - Relationship between echocardiographic and magnetic resonance derived measures of
      right ventricular size and function in patients with pulmonary hypertension.
AB  - BACKGROUND: Transthoracic echocardiographic (TTE) imaging is the mainstay of
      clinical practice for evaluating right ventricular (RV) size and function, but
      its accuracy in patients with pulmonary hypertension has not been well validated.
      METHODS: Magnetic resonance imaging (MRI) and TTE images were retrospectively
      reviewed in 40 consecutive patients with pulmonary hypertension. RV and left
      ventricular volumes and ejection fractions were calculated using MRI. TTE areas
      and indices of RV ejection fraction (RVEF) were compared. RESULTS: The average
      age was 42 +/- 12 years, with a majority of women (85%). There was a wide range
      of mean pulmonary arterial pressures (27-81 mm Hg) and RV end-diastolic volumes
      (111-576 mL), RVEFs (8%-67 %), and left ventricular ejection fractions (26%-72%)
      by MRI. There was a strong association between TTE and MRI-derived parameters: RV
      end-diastolic area (by TTE imaging) and RV end-diastolic volume (by MRI), R(2) =
      0.78 (P < .001); RV fractional area change by TTE imaging and RVEF by MRI, R(2) =
      0.76 (P < .001); and tricuspid annular plane systolic excursion by TTE imaging
      and RVEF by MRI, R(2) = 0.64 (P < .001). By receiver operating characteristic
      curve analysis, an RV fractional area change < 25% provided excellent
      discrimination of moderate systolic dysfunction (RVEF < 35%), with an area under
      the curve of 0.97 (P < .001). An RV end-diastolic area index of 18 cm(2)/m(2)
      provided excellent discrimination for moderate RV enlargement (area under the
      curve, 0.89; P < .001). CONCLUSIONS: Echocardiographic estimates of RV volume (by
      RV end-diastolic area) and function (by RV fractional area change and tricuspid
      annular plane systolic excursion) offer good approximations of RV size and
      function in patients with pulmonary hypertension and allow the accurate
      discrimination of normal from abnormal.

PMID- 24444662
TI  - Late onset simple schizophrenia.
AB  - Simple schizophrenia is a rarely used and controversial diagnosis. Here we report
      the case of a 54-year-old man with insidious changes in personality and
      behaviour, lacking perceptual abnormalities and delusions. He showed progressive
      inability in general functioning and self-care. He was diagnosed with simple
      schizophrenia and treated with antipsychotics, making a rapid and maintained
      recovery. We use this case to illustrate the continued relevance of the
      diagnosis, and highlight the risks of overlooking these patients, with
      significant consequences for their ability to function adequately in society. 

PMID- 24444663
TI  - The function of glycine decarboxylase complex is optimized to maintain high
      photorespiratory flux via buffering of its reaction products.
AB  - Oxidation of glycine in photorespiratory pathway is the major flux through
      mitochondria of C3 plants in the light. It sustains increased intramitochondrial
      concentrations of NADH and NADPH, which are required to engage the internal
      rotenone-insensitive NAD(P)H dehydrogenases and the alternative oxidase. We
      discuss here possible mechanisms of high photorespiratory flux maintenance in
      mitochondria and suggest that it is fulfilled under conditions where the
      concentrations of glycine decarboxylase reaction products NADH and CO2 achieve an
      equilibrium provided by malate dehydrogenase and carbonic anhydrase,
      respectively. This results in the removal of these products from the glycine
      decarboxylase multienzyme active sites and in the maintenance of their
      concentrations at levels sufficiently low to prevent substrate inhibition of the
      reaction. 

PMID- 24444664
TI  - Critical behaviour of nanocrystalline gadolinium: evidence for random uniaxial
      dipolar universality class.
AB  - We report on how nanocrystal size affects the critical behaviour of the rare
      earth metal Gd near the ferromagnetic-to-paramagnetic phase transition. The
      asymptotic critical behaviour of the coarse-grained polycrystalline sample (with
      an average crystallite size of L?100 MUm) is that of a (pure) uniaxial dipolar
      ferromagnet, as is the case with single crystal Gd, albeit the width of the
      asymptotic critical region (ACR) is reduced. As the grain size approaches ~30 nm,
      the ACR is so narrow that it could not be accessed in the present experiments.
      Inaccessibly narrow ACR for L ~ 30 nm and continuous increase in the width of the
      ACR as L decreases from 16 to 9.5 nm basically reflect a crossover to the random
      uniaxial dipolar fixed point caused by the quenched random exchange disorder
      prevalent at the internal interfaces (grain boundaries). 

PMID- 24444665
TI  - Disruption of Sertoli cell vimentin filaments in prepubertal rats: an acute
      effect of butylparaben in vivo and in vitro.
AB  - Parabens are p-hydroxybenzoic acid ester compounds widely used as preservatives
      in foods, cosmetics, toiletries and pharmaceuticals. We have recently shown that
      butylparaben induces spermatogenic cell apoptosis in prepubertal rats. We have
      conducted the present study for further information. Three-week-old male Sprague
      Dawley rats (n=8) were given a single oral dose of 1,000 mg/kg butylparaben. The
      rats were sacrificed under anesthesia at 3, 6 and 24h after administration and
      their testes were collected for histopathological and immunohistochemical
      examination. Results showed a gradual collapse of Sertoli cell vimentin filaments
      and decreased actin staining intensity without accompanying changes in the
      pattern of tubulin expression, while spermatogenic cells became separated from
      the basement membrane and sloughed into the lumen in the butylparaben-treated
      rats, compared to the controls. To determine the direct effects of butylparaben
      on Sertoli cells, primary Sertoli cell cultures with and without butylparaben
      treatment were examined. Toluidine blue staining in butylparaben treated-cultured
      Sertoli cells showed an increased number and size of vacuoles in their cytoplasm.
      In agreement with the in vivo experiment, the in vitro study also clearly
      demonstrated disruption of vimentin filaments in Sertoli cells after butylparaben
      treatment. Considering both our present and previous reports, we can speculate
      that butylparaben-induced disruption of Sertoli cell vimentin filaments may lead
      to precocious release of spermatogenic cells from underlying Sertoli cells, and
      the released cells may undergo apoptosis owing to loss of support provided by the
      Sertoli cells.

PMID- 24444667
TI  - Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague
      Dawley offspring.
AB  - MPH is a common treatment for adult Attention Deficit Hyperactivity Disorder
      (ADHD). However, little information exists regarding its safety during pregnancy
      and thus, women with ADHD face difficult decisions regarding continued use during
      pregnancy. Here, Sprague-Dawley rats were orally treated 3 */day with 0
      (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14
      mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs)
      1-21, all offspring/litter were orally treated 2 */day with the same dose.
      Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed.
      T3, T4, E2, testosterone, LH and corticosterone were measured at PND 22. Separate
      pregnant dams and resulting litters were used for serum MPH measurements. MPH
      treatment had mild, but significant, effects on gestational body weight and food
      intake. Birth weight of high MPH offspring was 5% more than controls (p<0.0500).
      Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more
      (p<0.0094), low MPH females weighed more (p<0.0001), while high MPH females
      weighed less (p<0.0397). PND 22 serum E2 levels were significantly decreased (20
      25%) in high MPH males and females (p<0.0500). Behavioral performance was
      unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were
      within the range produced by therapeutic MPH doses in adults; however, offspring
      levels in all groups were substantially higher. These results indicate that
      developmental MPH treatment has mild effects on gestational body weight and food
      intake and offspring preweaning body weight. Potential functional consequences of
      decreased serum E2 levels are not clear, but may impact later behavior or
      physiology.

PMID- 24444666
TI  - Empathic responsivity at 3 years of age in a sample of cocaine-exposed children.
AB  - This study examined the association between prenatal exposure to cocaine and
      behavioral and physiological responsivity. Participants were 216 mother-infant
      dyads (116 cocaine exposed-CE, 100 nonexposed-NCE) recruited at birth. Measures
      of heart rate (HR) and respiratory sinus arrhythmia (RSA) were obtained during
      baseline and during a task designed to elicit empathy (exposure to infant
      crying). When the effects of prenatal cocaine use were examined in the context of
      polydrug use, results of model testing indicated that lower gestational age,
      prenatal exposure to cocaine and postnatal exposure to alcohol were each
      associated with a reduced suppression of RSA during the empathy task. These
      findings provide additional support for an association between prenatal cocaine
      exposure and dysregulation during early childhood during affect-eliciting
      environmental challenges. 

PMID- 24444668
TI  - A novel framework for segmentation of secretory granules in electron micrographs.
AB  - It is still a standard practice for biologists to manually analyze transmission
      electron microscopy images. This is not only time consuming but also not
      reproducible and prone to induce subjective bias. For large-scale studies of
      insulin granules inside beta cells of the islet of Langerhans, an automated
      method for analysis is essential. Due to the complex structure of the images,
      standard microscopy segmentation techniques cannot be applied. We present a new
      approach to segment and measure transmission electron microscopy images of
      insulin granule cores and membranes from beta cells of rat islets of Langerhans.
      The algorithm is separated into two broad components, core segmentation and
      membrane segmentation. Core segmentation proceeds through three steps: pre
      segmentation using a novel level-set active contour, morphological cleaning and a
      refining segmentation on each granule using a novel dual level-set active
      contour. Membrane segmentation is achieved in four steps: morphological cleaning,
      membrane sampling and scaling, vector field convolution for gap filling and
      membrane verification using a novel convergence filter. We show results from our
      algorithm alongside popular microscopy segmentation methods; the advantages of
      our method are demonstrated. Our algorithm is validated by comparing automated
      results to a manually defined ground truth. When the number of granules detected
      is compared to the number of granules in the ground truth a precision of 91% and
      recall of 87% is observed. The average granule areas differ by 13.35% and 6.08%
      for core and membranes respectively, when compared to the average areas of the
      ground truth. These results compare favorably to previously published data. 

PMID- 24444669
TI  - Diffusion methods for aligning medical datasets: location prediction in CT scan
      images.
AB  - The purpose of this study is to introduce diffusion methods as a tool to label CT
      scan images according to their position in the human body. A comparative study of
      different methods based on a k-NN search is carried out and we propose a new,
      simple and efficient way of applying diffusion techniques that is able to give
      better location forecasts than methods that can be considered the current state
      of-the-art. 

PMID- 24444670
TI  - Favorable long-term outcomes of repeat endotherapy for small-intestine vascular
      lesions by double-balloon endoscopy.
AB  - BACKGROUND: GI bleeding secondary to small-intestine vascular lesions (SIVLs) is
      associated with rebleeding despite initial hemostasis by endotherapy applied at
      double-balloon endoscopy (DBE). OBJECTIVE: To evaluate the long-term outcomes of
      DBE endotherapy of SIVL (as described by the Yano-Yamamoto classification). The
      impact of repeat DBE endotherapy for recurrent bleeding also was assessed.
      DESIGN: Retrospective cohort study. The mean (+/- standard deviation [SD]) follow
      up period was 4.9 (+/- 1.7) years (range 2.4-9.1 years). SETTING: Tertiary-care
      referral center. PATIENTS: A total of 43 patients, who underwent 69 sessions of
      DBE endotherapy of SIVLs. INTERVENTION: DBE endotherapy. MAIN OUTCOME
      MEASUREMENTS: Frequency of overt rebleeding after the initial DBE endotherapy.
      RESULTS: Overt rebleeding occurred in 16 of 43 patients (37%). Patients with
      multiple SIVLs showed a significantly higher rate of overt rebleeding than did
      those with a solitary SIVL (12/23 [52%] vs 4/20 [20%]; P = .017). The trend
      toward frequency of rebleeding after the first DBE hemostasis appeared to be
      higher for patients with type 1a SIVLs than for those with type 1b or type 2
      lesions: type 1a (8/16, 50%) versus type 1b (5/19, 26%) (P = .12) and type 1a
      (8/16, 50%) versus type 2 (2/7, 29%) (P = .31), respectively. In 12 of 16
      patients (75%) who underwent repeat DBE endotherapy at each episode of overt
      rebleeding (median 3 times, range 2-6), the frequency of rebleeding decreased
      significantly after the first year of follow-up, as compared with the remaining 4
      patients who did not undergo repeat DBE; mean (+/- SD) 0.12 (+/- 0.19) versus
      0.52 (+/- 0.33) times per year per patient (P = .006). LIMITATIONS: Single
      center, retrospective study. CONCLUSION: Although the presence of multiple SIVLs
      was associated with rebleeding, repeat DBE endotherapy resulted in an improved
      long-term outcome in patients with refractory SIVL bleeding.

PMID- 24444671
TI  - Acetic acid spray enhances accuracy of narrow-band imaging magnifying endoscopy
      for endoscopic tissue characterization of early gastric cancer.

PMID- 24444672
TI  - Feasibility and outcomes of intravenous thrombolysis 3-4.5 hours after stroke in
      Chinese patients.
AB  - The time window for intravenous (IV) recombinant tissue plasminogen activator (rt
      PA) treatment in acute ischemic stroke (AIS) patients has been extended to 4.5
      hours. But little is known about the safety and efficacy of IV rt-PA treatment in
      the 3-4.5 hour time window in Chinese patients with AIS. A total of 119 patients
      who were treated with standard IV rt-PA therapy within 4.5 hours after symptom
      onset were included in this study: 85 were treated within 0-3 hours and 34 were
      treated within 3-4.5 hours. Favorable outcome was defined as a modified Rankin
      scale (mRS) score of 0-1 at 6 months. The safety of IV rt-PA treatment was
      assessed by the rate of mortality, symptomatic intracerebral hemorrhage (SICH)
      and other common complications. There were no significant differences in SICH
      rates (2.94% versus 2.35%; p=0.85) at 24-36 hours, mortality (5.88% versus 3.53%;
      p=0.56), other complications (14.71% versus 11.76%; p=0.66), National Institutes
      of Health Stroke Scale (NIHSS) score improvement at 24 hours (41.18% versus
      45.88%; p=0.64) and favorable mRS at 6 months (52.94% versus 54.12%; p=0.91)
      between the two time window groups. Multivariate analysis showed that advanced
      age, lower admission NIHSS score and shorter time from symptom onset to treatment
      were associated with a favorable clinical outcome. This finding showed an
      additional 29% of patients received IV rt-PA because of the treatment window
      expansion to 4.5 hours. IV rt-PA was feasible and safe for treating AIS patients
      in the 3-4.5 hour time window in our Chinese population.

PMID- 24444673
TI  - Preclinical research on pain comorbidity with affective disorders and cognitive
      deficits: Challenges and perspectives.
AB  - Affective disorders and cognitive deficits are common comorbidities of chronic
      pain in the clinical setting, which severely affect the quality of life of pain
      patients and impose a great difficulty upon clinical pain therapy. Despite large
      numbers of human studies examining this issue, there are surprisingly few reports
      investigating the comorbidities of chronic pain in animal models. This review
      summarizes and integrates previous reports of animal studies on pain and
      comorbidity, covering pain-evoked anxiety, depression, attentional deficits,
      cognitive impairment and locomotor dysfunction in rodents. Moreover, pain-induced
      alterations in synaptic plasticity are also discussed in terms of long-term
      potentiation and long-term depression, synaptic transmission, neuronal
      excitability and structural correlates in 'pain matrix'. Finally, we conclude
      this review by pointing out some unresolved problems and future research
      directions. 

PMID- 24444674
TI  - Utility of MS-MLPA in DNA methylation profiling in primary laryngeal squamous
      cell carcinoma.
AB  - OBJECTIVES: Methylation-specific multiplex ligation-dependent probe amplification
      (MS-MLPA) assay is a method that has rarely been exploited in DNA methylation
      profiling of laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS:
      Methylation of the gene was investigated by MS-MLPA in a well-characterized
      series of 53 LSCC and 30 samples of healthy mucosa. Aberrant promoter
      hypermethylation was confirmed using bisulfite pyrosequencing, and methylation
      specific. RESULTS: Promoter hypermethylation was observed in 36 of the 53
      patients (68%). CDKN2B (28%), APC (17%), RARbeta (15%), DAPK1 (11%) and CHFR
      (11%) were most frequently hypermethylated. Aberrant methylation of CHFR was
      mainly a late-stage event. Methylation-specific polymerase chain reaction and
      bisulfite pyrosequencing confirmed aberrant methylation for CDKN2B, APC and
      DAPK1. CONCLUSION: Promoter methylation profiling of LSCC using MS-MLPA
      identified CDKN2B, DAPK1, RARbeta, APC, and CHFR as frequent epigenetic events.
      The clinical implications of these genes as biomarkers are highly relevant as
      attractive targets for cancer therapy, given the reversible nature of epigenetic
      gene silencing.

PMID- 24444675
TI  - Evidence of lasting dysregulation of neuroendocrine and HPA axis function
      following global cerebral ischemia in male rats and the effect of Antalarmin on
      plasma corticosterone level.
AB  - Abnormal function of the neuroendocrine stress system has been implicated in the
      behavioral impairments observed following brain ischemia. The current study
      examined long-term changes in stress signal regulation 30days following global
      cerebral ischemia. Experiment 1 investigated changes in the expression of
      corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1),
      glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus
      (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the
      hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus
      (LC). Experiment 2 investigated the role of central CRHR1 activation on
      corticosterone (CORT) secretion at multiple time intervals following global
      ischemia after exposure to an acute stressor. Findings from Experiment 1
      demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at
      the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased
      LC TH expression in ischemic rats displaying working memory errors in the radial
      arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7
      days, but no longer present 14 and 21 days post ischemia. However upon an acute
      restraint stress induced 27 days following reperfusion, ischemic rats had
      increased plasma CORT secretions compared to sham-operated animals, suggesting
      HPA axis hypersensitivity. Antalarmin (2 MUg/2 MUl) pretreatment significantly
      attenuated post ischemic elevation of basal and stress-induced CORT secretion.
      These findings support persistent neuroendocrine dysfunctions following brain
      ischemia likely to contribute to emotional and cognitive impairments observed in
      survivors of cardiac arrest and stroke.

PMID- 24444676
TI  - [Therapeutic potential of Hibiscus sabdariffa: a review of the scientific
      evidence].
AB  - BACKGROUND AND OBJECTIVE: Infusion of Hibiscus sabdariffa (H. sabdariffa) is a
      very popular drink in many parts of the world. Its phytochemical composition is
      associated to antioxidant, hypotensive, and antiatherosclerotic effects. However,
      the molecular mechanisms involved in these processes are not well known. The aim
      of this review was to report the scientific evidence supporting that regular use
      of H. sabdariffa decreases oxidative stress, atherosclerosis, lipid profile, and
      blood pressure. MATERIAL AND METHODS: A search of recent publications was made in
      the following specialized electronic databases: Elsevier Journal, SciELO, FSTA,
      Science Direct, Springer Link, and NCBI. Results of research conducted in
      clinical trials in humans and in animal models and cell cultures were recorded.
      Keywords used included Hibiscus sabdariffa, oxidative stress, polyphenols,
      hypertension, atherosclerosis, and lipid profile. RESULTS: Results of the
      different articles suggested a possible therapeutic effect of H. sabdariffa
      extracts on oxidative stress, lipid profile, hypertension, and atherosclerosis
      thanks to its composition rich in phenolic compounds. Anthocyanins significantly
      decrease LDL oxidation, inhibit adipogenesis by regulating adipogenic signaling
      pathways and transcription factors, and modulate gene expression of certain
      microRNAs. No adverse events or side effects were reported. CONCLUSIONS: Further
      more homogeneous, placebo-controlled studies in humans are needed to state that
      H. sabdariffa has therapeutic efficacy in humans.

PMID- 24444677
TI  - Spinal epidural abscess in a diabetic patient.

PMID- 24444678
TI  - Low vital capacity is a predictor of incident diabetes in Japanese women.

PMID- 24444679
TI  - Palliative services enhance the quality and value of gynecologic cancer care.

PMID- 24444680
TI  - Burn care experts and burn expertise.
AB  - In addressing the sometimes complex problems surrounding burn wounds and their
      treatments, everyone wants treatment to be provided by an expert. But who is an
      expert and what constitutes expertise? This article discusses the issues of
      expertise in the context of burn care and highlights challenges and risks to the
      maintenance of expertise in the modern clinical environment. 

PMID- 24444681
TI  - Model based 3D CS-catheter tracking from 2D X-ray projections: binary versus
      attenuation models.
AB  - Tracking the location of medical devices in interventional X-ray data solves
      different problems. For example the motion information of the devices is used to
      determine cardiac or respiratory motion during X-ray guided procedures or device
      features are used as landmarks to register images. In this publication an
      approach using a 3D deformable catheter model is presented and used to track a
      coronary sinus (CS) catheter in 3D plus time through a complete rotational
      angiography sequence. The benefits of using voxel based models with attenuation
      information for 2D/3D registration are investigated in comparison to binary
      catheter models. The 2D/3D registration of the model allows to extract a 3D
      catheter shape from every individual 2D projection. The tracking accuracy is
      evaluated on simulated and clinical rotational angiography data of the contrast
      enhanced left atrium. The quantitative evaluation of the experiments delivers an
      average registration accuracy for all catheter electrodes of 0.23 mm in 2D and
      0.95 mm in 3D when using an attenuation model of the catheter. The overall
      tracking accuracy is lower when using binary catheter models.

PMID- 24444683
TI  - [Thinking of laparoscopic anatomy of laparoscopic distal D2 radical gastrectomy].
AB  - OBJECTIVE: To discuss laparoscopic assisted radical D2 resection of distal
      gastric anatomy application ideas. METHODS: Collected the clinical data from
      January 2009 to January 2012 who underwent laparoscopic distal gastric resection
      in patients with D2 349 cases. There were 180 male and 169 female patients, and
      the age were (57 +/- 3) years old (range 29-86 years), the body mass index of
      patients were (26.0 +/- 2.0) kg/m(2) (range 20.5-32.8 kg/m(2)). The relevant
      surgical anatomy ideas had summarized. RESULTS: In addition to 5 cases of obese
      patients with conversion to open, the remaining patients underwent laparoscopic
      distal gastric D2 resection. The operation is divided into 7 operating anatomical
      view. The operation time were 120-210 minutes and the blood loss were 50-200 ml.
      Postoperative complications occurred in 11 cases, including 5 cases of duodenal
      stump leakage, 2 cases of gastroparesis, 3 cases of small bowel obstruction, and
      abdominal bleeding in 1 case. All patients were discharged. CONCLUSIONS: Use
      zoning, exterior to interior of the anatomy, more conducive to master the
      operation of laparoscopic radical gastrectomy and standardized cleaning, to
      improve the operation efficiency and shorten the surgical learning curve and
      improve the quality of surgery has an important role.

PMID- 24444682
TI  - [The role of perioperative enteral and parenteral nutrition treatment in
      pancreatic cancer: a multicenter, prospective randomized controlled trial].
AB  - OBJECTIVE: To compare the two different nutritional supports, enteral nutrition
      and parenteral nutrition in the aspects of nutritional conditions, immune status,
      the incidence of perioperative complications and quality of life impacts in
      pancreatic cancer. METHODS: For the pancreatic cancer patients which
      pancreaticoduodenectomy were performed from January 2007 to December 2008 in five
      high-volume medical centres, prospective, randomized controlled study was carried
      out. The enrolled patients were randomly divided into enteral nutritional group
      (EN group) and parenteral nutritional group (PN group). Related indicators, such
      as nutritional conditions, immune status, incidence of complications, general
      status and quality of life were assessed. RESULTS: The 200 patients were
      enrolled, while 178 cases which 90 patients in EN group and 88 patients in PN
      group were qualified to evaluate. The 22 cases were dropped out. For the mean
      hospital stay ((23 +/- 13) days and (27 +/- 24) days respcectively), Karnofsky
      score and the life quality scoring, there are no statistical differences between
      the two groups. In post-operation day 7 and day 10, the prealbumin was (69 +/-
      16) mg/L and (80 +/- 22) mg/L in EN group and it was (67 +/- 19) mg/L and (70 +/-
      11) mg/L in PN group, which are all significantly decreased than preoperational
      levels ((186 +/- 38) mg/L for enteral group and (179 +/- 37) mg/L for parenteral
      group, t = -2.24, -2.13, -2.23, -2.20, all P < 0.05), but there was no
      statistically significant between the 2 groups (P > 0.05). Other general
      indicators such as the albumin, hemoglobin, total bilirubin, blood urea nitrogen,
      serum creatinine, serum potassium and serum sodium, revealed no statistical
      differences in the 2 groups (P > 0.05); The total lymphocytes, CD(+)3CD(+)4 and
      CD(+)3CD(+)8 lymphocytes in PN group was (0.687 +/- 0.065)*10(9)/L, (0.363 +/-
      0.029)*10(9)/L, and (0.183 +/- 0.018)*10(9)/L respectively in post-operation day
      10, which they are significantly decreased than in preoperational levels of PN
      group and the respective counterpart of EN group in post-operation day10 (t = 
      2.04-2.83, P < 0.05). The 35 patients were suffered from different complications
      in the 2 groups, but there was no statistical differences among them (P > 0.05).
      CONCLUSIONS: Enteral nutritional support could not decrease the incidence of
      perioperative complications in pancreatic cancer patient, but it can improve the
      immunonutrition status in comparison with parenteral nutrition.

PMID- 24444684
TI  - [A procedure to assist achievement of total mesorectal excision through the
      extending intersphincteric plane].
AB  - OBJECTIVE: To investigate the value of assisted achievement total mesorectal
      excision (TME) through the extending intersphincteric plane. METHODS: From
      February 2006 to April 2010, 65 patients with low rectal cancer underwent
      assisted implementing TME through the extending intersphincteric plane under
      direct vision and achieved sphincter preservation. The clinical data was
      summarized and analyzed retrospectively. Follow-up visits were conducted on
      complications and oncological outcomes. RESULTS: The mean operation time was (245
      +/- 42) minutes, and the mean intraoperative blood loss was (114 +/- 76) ml.
      There was no postoperative mortality. Postoperative complications included 2
      cases of anastomotic leak, 13 cases of anastomotic stenosis, 2 cases of early
      postoperative inflammatory ileus, 1 case of urinary tract infection, and 1 case
      of incision infection. Distal margins and circumferential resection margin of all
      specimens were negative. For pathological stage, there were 26 cases at stage
      pTNMI, 17 cases at stage pTNMII and 22 cases at stage pTNMIII. The mean follow-up
      time was (47.9 +/- 18.9) months. 10 patients were lost to follow up, 15 cases had
      distant metastasis or local recurrence in, and 8 cases died of tumor metastasis
      at the latest follow up. Local recurrence occurred in 3 cases, including
      recurrence in presacral region, metastasis of lymph node at the left side in
      pelvis cavity, and metastasis at the sacrum at 35, 36, and 52 months
      postoperatively. There was no anastomotic recurrence. Log-rank survival analysis
      showed 5-year cumulative survival rate was 100%, 93.3%, and 63.1% in TNM stage I,
      II, and III, respectively. The cumulative disease-free survival rate was 96.2%,
      83.3%, 44.8% in TNM stage I, II, and III, respectively. CONCLUSION: It has a good
      oncological effect and was an advantageous procedure to assist achievement total
      mesorectal excision (TME) through the extending intersphincteric plane as
      surgeons encountered with difficulties from transabdominal TME.

PMID- 24444685
TI  - [Analysis of prognostic factors related to triple-negative breast cancer].
AB  - OBJECTIVE: To investigate the prognostic factors related to triple-negative
      breast cancer (TNBC) by analyzing clinicopathologic characteristics, treatment
      and prognosis. METHODS: Three hundred and five TNBC patients treated between
      January 2004 and December 2011 were enrolled and retrospectively reviewed with
      Kaplan-Meier and Cox proportional hazards models. All patients were females and
      the age onset were 24-82 years old (the median were 50 years old). RESULTS: The
      follow-up period was 1 to 114 months, with median 38 months. The 5-year disease
      free survival (DFS) rate was 68% and overall survival (OS) rate 75%. The peak
      risk of recurrence occurs within the first 2-3 years after initial treatment of
      the disease, but distant relapse after this time is much less common. Survival
      analysis showed that surgery type (chi(2) = 4.030, P = 0.045), tumor grade
      (chi(2) = 8.000, P = 0.046), lymph-vascular invasion (chi(2) = 10.386, P = 0.001)
      and lymph node stage (chi(2) = 119.36, P = 0.000), TNM stage (chi(2) = 65.961, P
      = 0.000) and treatment plan (chi(2) = 28.371, 21.874, 32.163, all P = 0.000) were
      statistically related to DFS; while age (chi(2) = 10.226, P = 0.006), lymph
      vascular invasion (chi(2) = 18.881, P = 0.000), lymph node stage (chi(2) =
      98.958, P = 0.000), TNM stage (chi(2) = 65.342, P = 0.000) and type of treatment
      (chi(2) = 17.862, 18.708, 31.921, all P = 0.000) were related to OS. The lymph
      nodes stage was prognostic factor related to both DFS and OS. CONCLUSIONS: TNBC
      was characterized by poor prognosis and rapid progression. The lymph nodes
      metastatic status was the most important prognostic factor of TNBC.

PMID- 24444686
TI  - [Preliminary clinical results of endoscopic assisted anterior lumbar interbody
      fusion].
AB  - OBJECTIVE: To summarize the experiences of endoscopic assisted anterior lumbar
      interbody fusion (ALIF) with self-locking cage via retroperitoneal approach
      through small incision lateral to abdominal rectus. METHODS: There were 47 cases
      of endoscopic assisted ALIF from April 2010 to April 2012 were reviewed
      retrospectively, including 28 male and 19 female patients whose age ranged from
      39 to 65 years, averaged of (48 +/- 11) years. Of 47 cases, 17 cases were founded
      instability in lumbar spine, 16 cases of discogenetic low back pain, 7 cases of
      degenerative spondylolithesis, and 7 cases of recurrent disc herniation. The
      level involved included 7 cases at L3-4 level, 33 cases at L4-5 level, 7 cases at
      L5-S1. X-ray and/or 3D CT scan were done in each patient at post-operative day 4,
      1 month, 3 months, and 6 months. The height and angle of disc space, angle of
      lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope
      (SS) were recorded and measured, as well as length of incision, operation time,
      blood loss, complications and ratio of bone graft fusion. The clinical outcomes
      were evaluated by Oswestry disability index (ODI) and visual analogue scale
      (VAS). RESULTS: Average length of incision was (6.2 +/- 0.8)cm (5.3-7.8 cm) ,
      average blood loss was (81 +/- 20)ml (50-150 ml) , mean operation time was (96 +/
      10)minutes (65-122 minutes) . There were significant improvement of ODI(48% +/-
      10% vs. 14% +/- 5%), the VAS of back pain(6.3 +/- 1.1 vs.0.7 +/- 0.7) and VAS of
      leg pain(3.4 +/- 2.1 vs.0.6 +/- 0.6) during preoperative and postoperation last
      follow-up (t = 20.78, 25.92 and 8.74, P = 0.000). The disc height of operative
      segments were all recovered significantly (F = 18.971, P = 0.000)
      postoperatively, from preoperative (10.3 +/- 2.4)mm to postoperative (12.6 +/-
      2.1)mm. For complications, 5 cases had peritoneum tear, 19 cases had bone donor
      site pain, 14 cases had abdominal distension and 5 cases had lower limb
      paraesthesia, which were all treated with supportive managements. Bony
      intervertebral fusion was obtained in all cases in 6 months postoperatively.
      CONCLUSIONS: The advantages of endoscopic assisted ALIF with self-locking cage
      via retroperitoneal approach are less damage, rapid recovery, and less blood
      loss. Comparing with traditional ALIF procedure, the view of operative field is
      also improved.

PMID- 24444687
TI  - [Pre-operative assessment of the patellofemoral joint in unicompartmental knee
      replacement using Oxford Phase III and its influence on outcome].
AB  - OBJECTIVE: To determine whether anterior knee pain and/or radiological evidences
      of degeneration of the patellofemoral joint influence the outcome of
      unicompartmental knee arthroplasty (UKA). METHODS: Between January 2006 and
      December 2010, 95 consecutive patients (100 knees) with unicompartmental knee
      osteoarthritis were treated with Oxford UKA, including 34 males and 61 females.
      The mean age was 68.2 years (range, 55-82 years). The average Body Mass Index was
      26.3 kg/m(2)(range, 24-28 kg/m(2)). Pre-operative there were 43 knees (43.0%)
      with anterior knee pain and 57 knees (57.0%) without it. Pre-operative
      radiological status of the patellefemoral joint were defined using Ahlback and
      Altman systems. The pre- and post-operative results of Oxford Knee Score (OKS),
      American Knee Society Score (AKS) and Western Ontario and Macmaster (WOMAC) were
      compared using paired t-test, the results between different groups were compared
      using grouped t-test. RESULTS: All cases were followed up for average 50 months
      (24-84 months). At the last follow-up, none had complications of infection, fat
      embolism, deep vein thrombosis, malposition of prosthesis, dislocation or
      loosing. The mean femoral component alignment was -0.7 degrees  +/- 5.2 degrees 
      (valgus/varus), -0.8 degrees  +/- 4.5 degrees (flexion/extension); the mean
      tibial component alignment was -0.1 degrees  +/- 2.2 degrees (valgus/varus), -0.4
      degrees  +/- 2.4 degrees  (flexion/extension). The clinical outcomes were
      significantly improved compared with pre-operation regardless of presence (OKS: t
      = 19.04, P < 0.01; AKS knee:t = 38.56, P < 0.01;AKS function:t = 39.29, P <
      0.01;WOMAC:t = 43.22, P < 0.01) or absence (OKS: t = 31.57, P < 0.01; AKS knee:t
      = 40.34, P < 0.01; AKS function:t = 43.62, P < 0.01; WOMAC: t = 47.06, P < 0.01)
      of anterior knee pain. The results were significantly improved compared with pre
      operation (P < 0.01) regardless of whether degeneration of the patellofemoral
      joint. There was no statistically significant difference in outcome between
      patients with evidence of degeneration in the medial patellofemoral joint and
      those without (P > 0.05) . Patients with lateral patellofemoral degeneration had
      a worse score than those without, OKS (t = 2.56, P = 0.01) and WOMAC (t = 2.20, P
      = 0.03) by the Altman score, OKS (t = 2.29, P = 0.02) by the Ahlback score. For
      AKS measures there was no statistically significant difference in outcome (P >
      0.05) . CONCLUSIONS: Neither anterior knee pain nor radiological evidence of
      medial patellofemoral joint degeneration would influnence the outcome of UKA,
      lateral patellofemoral joint degeneration have an increased risk of a poor
      result.

PMID- 24444688
TI  - [Clinical factors influencing surgical approach selection of robotic-enhanced
      minimally invasive coronary artery bypass grafting].
AB  - OBJECTIVE: To investigate clinical factors that influence the selection of
      minimally approach between minimally invasive direct coronary artery bypass
      (MIDCAB) and totally endoscopic coronary artery bypass (TECAB). METHODS: From
      February 2007 to January 2013, patients were selected under uniform criteria. A
      total of 202 patients including 142 male and 60 female patients with age range
      from 33 to 80 years and average age of (59 +/- 10) years were included and were
      all routinely prepared for TECAB. Either TECAB or MIDCAB was performed based on
      the intraoperative condition. There were 90 patients who underwent TECAB (TECAB
      group) and 112 patients who received MIDCAB surgery (MIDCAB group). Univariate
      analysis was used to compare preoperative, intraoperative and early postoperative
      parameters. Logistic multivariate regression analysis was used to discuss
      independent influencing factors of minimally invasive approach selection.
      RESULTS: All of the patients successfully received TECAB or MIDCAB surgery
      without mortality, severe complications or conversion to sternotomy. The early
      and midterm follow up of graft patency (by computed tomography angiography) was
      satisfactory. The mean operative time was (160 +/- 64)minutes, mean graft flow
      was (27 +/- 18) ml/min. Univariate analysis showed that sex ratio (3.5 vs.1.8, t
      = 4.350, P = 0.037), weight [(69 +/- 11)kg vs.(72 +/- 11)kg, t = -1.979, P =
      0.049], multivessel coronary disease (43.3% vs.60.7%, t = 6.051, P = 0.014), and
      learning curve case (4.4% vs.14.3%, t = 5.418, P = 0.02) were significant
      predictors of conversion to MIDCAB. By multivariate analysis, multivessel
      coronary disease (HR = 1.964, 95%CI: 1.049-3.680, P = 0.035) and learning curve
      case (HR = 4.538, 95%CI: 1.219-16.891, P = 0.024) were independent influencing
      factors of MIDCAB approach. CONCLUSIONS: Robotic-assisted minimally invasive
      coronary artery bypass grafting can be performed safely and effectively either by
      TECAB or MIDCAB. Multivessel coronary disease and early learning curve cases are
      independent influencing factors of minimally invasive approach selection.

PMID- 24444689
TI  - [Brain mappings in non-fluent late Chinese-English bilinguals].
AB  - OBJECTIVE: To discuss the distribution characteristics of language areas in
      Chinese-English non-fluent late bilinguals. METHODS: Six Chinese-English
      bilinguals with eloquent tumors underwent awake-surgeries. The activated areas of
      BOLD-fMRI were obtained as the patients performed pure naming, verb generation,
      and abstract/concrete judgment tasks. Direct cortical stimulation(DCS) as the
      golden standard of language mapping were performed during awake-surgeries on the
      exposed cortical areas. BOLD-fMRI results of 3 language tasks were compared with
      DCS results. The statistical method was McNemer. RESULTS: Sixteen positive
      sites(22.5%) were comfirmed out of 71 stimulations. There were 3 specific
      language sites, in which 2 sites were specific English sites and 1 site was
      specific Chinese site. When activated areas of BOLD-fMRI were compared with the
      DCS results, verb generation task had the highest concordance rate 40.9%
      (95%CI:30.2%-52.5%) . There were significant differences between the results of
      BOLD-fMRI and DCS of all 3 bilingual tasks(P < 0.017). CONCLUSIONS: There are
      specific language areas in Chinese-English non-fluent late bilinguals. The BOLD
      fMRI language mapping could not substitute DCS in the context of mapping language
      areas in bilinguals.

PMID- 24444690
TI  - [RIN1 expression in hepatocellular cancer and the affection on prognosis and
      tumor invasion ability].
AB  - OBJECTIVE: To test the expression of RIN1 in hepatocellular cancer (HCC) and
      study its clinicopathological significance and mechanism. METHODS: RIN1 mRNA in
      36 HCC tissues was analyzed using real-time PCR (RT-PCR). The expression of RIN1
      was examined by immunohistochemistry (IHC) in 110 HCC specimens. The relationship
      between the protein expression and prognosis was analyzed. Transwell was used to
      test invasion ability of HCC cell lines which were transfected with the
      expression vector pEGFP-N1-RIN1. RESULTS: RIN1 mRNA expression levels was much
      lower in tumor tissues than that in their corresponding non-cancerous tissues
      (chi(2) = 7.430, P = 0.026). RIN1 protein was lowly expressed in liver cancer
      samples (69.1%) and correlated with poor survival (6.46%) (chi(2) = 13.808, P <
      0.05). Transwell assays show that RIN1 overexpression can inhibit invasion
      ability of HepG2 cells (t = 8.975 and 9.522, both P < 0.05). RIN1 expression and
      ABL2 and E calcium protein were positively correlated (r = 0.898 and 0.912, P <
      0.05), and negatively correlated with MMP-9 (r = -0.933, P = 0.002). CONCLUSIONS:
      RIN1 expression was down-regulated in HCC and low expression of RIN1 foreshows
      poor prognosis of HCC patients. RIN1 overexpression can inhibit invasion ability
      of HepG2 cells.

PMID- 24444691
TI  - [The effect of sympathectomy on the development and progression of scoliosis in
      bipedal mice model].
AB  - OBJECTIVE: To investigate the effect of sympathectomy on the development and
      progression of scoliosis in bipedal C57BL/6J mice model. METHODS: Sixty female 3
      week-old C57BL/6J mice were selected to establish bipedal scoliotic mice model
      after amputations of forelimbs and tails. All mice were randomly divided into
      three groups, 20 mice for each group. Group 1 received daily intraperitoneal
      injection of 0.9% saline (5 mg/kg); while Group 2 and 3 received sympathectomy by
      daily intraperitoneal injection of propranolol (20 mg/kg) and guanethidine
      sulfate (40 mg/kg), respectively. Posteroanterior X-rays were obtained at 20th
      week. Curves were measured using Cobb method and scoliosis was defined as a Cobb
      angle of > 10 degrees . Incidence of scoliosis and severity of curves were
      compared among groups using Chi-square test and One-way analysis of variance,
      respectively. RESULTS: There were 17 (85.0%) mice presented scoliosis in Group 1;
      whereas 11 (55.0%) and 10 (50.0%) mice presented scoliosis in Group 2 and 3,
      respectively. The incidence of scoliosis was found to be higher in Group 1, and
      the difference was statistically significant (chi(2) = 6.172, P = 0.046). As for
      curve magnitudes, the mean Cobb angle was 20 degrees  +/- 9 degrees  in Group 1,
      10 degrees  +/- 7 degrees  in Group 2, and 12 degrees  +/- 8 degrees  in Group 3.
      The mean Cobb angle of Group 1 was significantly greater than those of Group 2
      and 3 (F = 9.545, P < 0.001), but there was no significant difference in mean
      Cobb angle between Group 2 and 3. CONCLUSIONS: Sympathetic nervous system may be
      involved in the development and progression of scoliosis in bipedal C57BL/6J mice
      model. Sympathectomy do not seem to dramatically decrease the incidence of
      scoliosis, probably due to that bipedalism itself may also be a cause of
      scoliosis in this animal model.

PMID- 24444692
TI  - [A meta-analysis on short and long term efficacy and safety of procedure for
      prolapse and hemorrhoids].
AB  - OBJECTIVE: To Systematic review and meta-analysis of short and long term efficacy
      and safety of procedure for prolapse and hemorrhoids. METHODS: Electronic
      databases including Cochrane Library, PubMed, OVID, SpringerLinker, ScinceDirect,
      EBSCO, CNKI, VIP, WanFang Data and CBM were searched. The date of search was
      between January 2000 and January 2013. Randomized controlled trials (RCTs) were
      indentified studying association of Compare PPH and Milligan-Mogan (MMH)
      treatment. Study selection and meta-analysis were conducted according to the
      Cochrane Handbook for RevMan 5.1 software. RESULTS: The trials involving 1343
      patients were included. The results of meta-analysis indicated: compared with
      MMH, PPH operative time (OR = -11.05, 95%CI: -15.15--6.95, P < 0.01), duration of
      hospitalization (OR = -3.07, 95%CI: -4.46--1.69, P < 0.01) and return to normal
      activity time (OR = -7.17, 95%CI: - 9.13--5.20, P < 0.01) was short,
      postoperative pain light (OR = -3.13, 95%CI: -4.38--1.88, P < 0.01), but the high
      cost of treatment (OR = 2534.2, 95%CI: 509.0-4559.4, P = 0.01). Long-term
      efficacy, PPH was higher patient satisfaction (OR = 2.21, 95%CI: 1.03-4.75, P =
      0.04), but the recurrence rate of prolapse (OR = 3.75, 95%CI: 1.75-8.06, P <
      0.01) and reoperation rate (OR = 7.90, 95%CI: 1.78-35.03, P < 0.01) higher. The
      incidence of anal stenosis and anal incontinence postoperative were higher than
      MMH (P > 0.05). The difference of post operative anal stenosis and anal
      incontinence and residual skin tag rate were not statistically significant (all P
      > 0.05). CONCLUSIONS: PPH surgery can be used as replacement therapy of MMH for
      III degrees -IV degrees  prolapsed hemorrhoids. But we should inform patients of
      prolapse recurrence and reoperation risk of PPH in the long term.

PMID- 24444694
TI  - Evolution of a mesoporous bioactive glass scaffold implanted in rat femur
      evaluated by (45)Ca labeling, tracing, and histological analysis.
AB  - Mesoporous bioactive glass (MBG) as a biodegradable scaffold with a nanostructure
      has attracted significant attention. However, the in vivo evolution of MBG, which
      includes in situ degradation, the local effect induced by degradation, and the
      disposition of degradation products, remains unclear. In this study, we performed
      in situ labeling and synthesis of an MBG scaffold for the first time using
      (45)CaCl2. The obtained (45)Ca-MBG scaffolds possessed a mesoporous-macroporous
      cross-linked structure. These (45)Ca-MBG scaffolds were implanted in critical
      sized rat femur defects (3 * 3 mm) for 1 day and for 1, 4, 8, and 12 weeks and
      analyzed by isotopic quantitative tracing. The results illustrated that the MBG
      scaffolds gradually degraded over time and persisted at a local level of
      approximately 9.63% at week 12. This finding suggests that only a very small
      amount of MBG-released calcium ions may have been transformed into calcium
      components of the new bone matrix. The research also confirmed that the active
      ingredients derived from the degradation of MBG scaffolds could actively regulate
      the mRNA expression levels of osteoblast-related genes in rat bone marrow-derived
      mesenchymal stem cells (rBMSCs) and promote bone regeneration in vivo. Moreover,
      through isotopic tracing of the entire body, (45)Ca, which disappeared in situ
      after implantation, could be detected in the heart, lungs, spleen, kidneys,
      intestines, and brain via the blood and was mainly accumulated in distal bone
      tissue, including the radius and cranium. However, (45)Ca radioactivity in the
      body tissues significantly decreased or disappeared after 12 weeks. Systemic
      toxicological studies on MBG scaffolds demonstrated the degradation products that
      spread to major organs did not cause abnormal histopathological changes. The
      above discoveries comprehensively address crucial issues regarding the
      application of MBG in vivo, and these findings provide a scientific basis for
      introducing a material with mesoporous structure into clinical applications. 

PMID- 24444695
TI  - Evaluation of intravenous lipid emulsion on haloperidol-induced hypotension in
      rabbits.
AB  - There are many reports on the effects of intravenous lipid emulsion (ILE) as an
      antidote in drug toxicity. Haloperidol (HAL) is a butyrophenone antipsychotic
      agent which is highly lipophilic. Hypotension is an important adverse effect of
      HAL administration and overdose. The aim of this study was to investigate the
      beneficial hemodynamic effects of ILE on acute HAL poisoning. We used six groups
      of five male rabbits. Two groups received aseptic distilled water intravenously
      followed by infusion of 18.6 ml/kg normal saline, as negative control group, or
      ILE 20% after 0.5 h. The third group received 18.6 ml/kg normal saline after HAL
      infusion (2.6 mg/kg). The other three groups received ILE 20% solution (6, 12,
      and 18.6 ml/kg) following HAL (2.6 mg/kg) administration. We measured blood
      pressure at 0, 0.5, 1, 2, 3, 4, 8, and 24 h after starting HAL administration,
      from left forelimb using a noninvasive method that was carried out automatically
      with a neonatal intensive care unit bedside monitor. ILE 20% at the dose of 18
      ml/kg could return the reduced mean arterial pressure and diastolic blood
      pressure sooner than the other doses and normal saline. In conclusion, ILE could
      reverse HAL-induced hypotension same as the other lipophilic drugs. However, the
      clinical use of ILE for this purpose needs more evaluation to determine its exact
      indication and safety. 

PMID- 24444693
TI  - Noise in biology.
AB  - Noise permeates biology on all levels, from the most basic molecular, sub
      cellular processes to the dynamics of tissues, organs, organisms and populations.
      The functional roles of noise in biological processes can vary greatly. Along
      with standard, entropy-increasing effects of producing random mutations,
      diversifying phenotypes in isogenic populations, limiting information capacity of
      signaling relays, it occasionally plays more surprising constructive roles by
      accelerating the pace of evolution, providing selective advantage in dynamic
      environments, enhancing intracellular transport of biomolecules and increasing
      information capacity of signaling pathways. This short review covers the recent
      progress in understanding mechanisms and effects of fluctuations in biological
      systems of different scales and the basic approaches to their mathematical
      modeling. 

PMID- 24444696
TI  - Royal jelly attenuates azathioprine induced toxicity in rats.
AB  - In the present study, we investigated the potential protective effects of royal
      jelly against azathioprine-induced toxicity in rat. Intraperitoneal
      administration of azathioprine (50 mg/kgB.W.) induced a significant decrease in
      RBCs count, Hb concentration, PCV%, WBCs count, differential count and platelet
      count, hepatic antioxidant enzymes (reduced glutathione and glutathione s
      transferase) and increase of serum transaminases (alanine aminotransferase and
      aspartate aminotransferase enzymes) activities, alkaline phosphatase and
      malondialdehyde formation. Azathioprine induced hepatotoxicity was reflected by
      marked pathological changes in the liver. Oral administration of royal jelly (200
      mg/kgB.W.) was efficient in counteracting azathioprine toxicity whereas it
      altered the anemic condition, leucopenia and thrombocytopenia induced by
      azathioprine. Furthermore, royal jelly exerted significant protection against
      liver damage induced by azathioprine through reduction of the elevated activities
      of serum hepatic enzymes. Moreover, royal jelly blocked azathioprine-induced
      lipid peroxidation through decreasing the malondialdehyde formation. In
      conclusion, royal jelly possesses a capability to attenuate azathioprine-induced
      toxicity.

PMID- 24444697
TI  - Effects of cigarette smoke on Holter ECG recordings in patients with arterial
      hypertension. Part 1: Time domain parameters of heart rate variability.
AB  - This report was intended to evaluate the effect of cigarette smoke on heart rate
      variability (HRV) in patients with arterial hypertension (AH). 223 individuals
      were qalified to the studies. The following groups of patients not suffering from
      other disease which may affect HRV were delineated: 1 - patients with AH (n=145);
      2 - patients without AH (n=48). In group 1 the following patient groups were
      studied: A - active smokers (n=42), B - non-smokers exposed to cigarette smoke
      (n=30), C - non-smokers not exposed to tobacco smoke (n=34), D - former smokers
      (n=26). A time domain HRV analysis was carried out. Group 1 versus group 2
      manifested significantly lower mean values of most parameters in the HRV time
      domain analysis. Subgroups A, B and D versus subgroup C also exhibited
      significantly lower mean values of most parameters in the HRV time domain
      analysis. Active cigarette smoking and passive exposure to tobacco smoke
      represented independent risk factors for a decreased HRV. CONCLUSIONS: Active and
      passive exposure to cigarette smoke decreases HRV in hypertensive patients.

PMID- 24444698
TI  - Summing-coincidence corrections with Geant4 in routine measurements by gamma
      spectrometry of environmental samples.
AB  - In this work, we describe a method to quantitatively evaluate true-coincidence
      summing effects by making use of the Geant4 toolkit, which incorporates an
      emulation of the radionuclide disintegration scheme. To check the capabilities of
      the method, we firstly validated the simulated corrections using the ones
      obtained experimentally for radionuclides such as (60)Co, (152)Eu and (133)Ba.
      Secondly, we evaluated the effect of summing corrections of some radionuclides
      included in two intercomparison exercises to conclude that the results were
      improved when utilising the method described here. 

PMID- 24444699
TI  - Uncertainty evaluation in radon concentration measurement using charcoal
      canister.
AB  - Active charcoal detectors are used for testing the concentration of radon in
      dwellings. The method of measurement is based on radon adsorption on coal and
      measurement of gamma radiation of radon daughters. The contributions to the final
      measurement uncertainty are identified, based on the equation for radon activity
      concentration calculation. Different methods for setting the region of interest
      for gamma spectrometry of canisters were discussed and evaluated. The obtained
      radon activity concentration and uncertainties do not depend on peak area
      determination method. 

PMID- 24444700
TI  - Complexity and the science of implementation in health IT--knowledge gaps and
      future visions.
AB  - OBJECTIVES: The intent of this paper is in the examination of health IT
      implementation processes - the barriers to and facilitators of successful
      implementation, identification of a beginning set of implementation best
      practices, the identification of gaps in the health IT implementation body of
      knowledge, and recommendations for future study and application. METHODS: A
      literature review resulted in the identification of six health IT related
      implementation best practices which were subsequently debated and clarified by
      participants attending the NI2012 Research Post Conference held in Montreal in
      the summer of 2012. Using the framework for implementation research (CFIR) to
      guide their application, the six best practices were applied to two distinct
      health IT implementation studies to assess their applicability. RESULTS:
      Assessing the implementation processes from two markedly diverse settings
      illustrated both the challenges and potentials of using standardized
      implementation processes. In support of what was discovered in the review of the
      literature, "one size fits all" in health IT implementation is a fallacy,
      particularly when global diversity is added into the mix. At the same time,
      several frameworks show promise for use as "scaffolding" to begin to assess best
      practices, their distinct dimensions, and their applicability for use.
      CONCLUSIONS: Health IT innovations, regardless of the implementation setting,
      requires a close assessment of many dimensions. While there is no "one size fits
      all", there are commonalities and best practices that can be blended, adapted,
      and utilized to improve the process of implementation. This paper examines health
      IT implementation processes and identifies a beginning set of implementation best
      practices, which could begin to address gaps in the health IT implementation body
      of knowledge.

PMID- 24444701
TI  - Diagnosis and classification of immune-mediated thrombocytopenia.
AB  - Immune thrombocytopenia, or ITP, has been recognized as a clinical entity for
      centuries, and the importance of humoral mechanisms in the pathophysiology of ITP
      has been recognized for decades. Despite the long history of the syndrome,
      progress in understanding its epidemiology and management has been hindered by
      inconsistencies in nomenclature and classification schema together with the
      inherent heterogeneity in characteristics of global populations and ITP
      associated disorders. In the past decade, great strides have been made in
      devising a common language for caregivers and investigators alike through
      standardization definitions and outcome measures, while new tools have become
      available for management of its clinical manifestations. In 2009, an
      International Working Group presented proposed standards for definitions,
      classification criteria, and outcome measures. The American Society of Hematology
      adopted these standards in 2011, including them in that body's guideline for
      immune thrombocytopenia. Despite the progress made so far, 20th century
      interventions such as corticosteroids and IVIg remain the mainstay of therapy.
      However, advances in treatment have led to the introduction of targeted therapies
      for select patients with chronic disease. In this paper, we review aspects of the
      epidemiology and pathophysiology of ITP and discuss the recent changes in
      guidelines for nomenclature, diagnosis, and treatment. 

PMID- 24444702
TI  - Self-focused thinking predicts nighttime physiological de-arousal.
AB  - Excessive focus on the internal self has maladaptive consequences for mental and
      physical health. Although the emotional functions of self-focus have been well
      established, no study has examined physiological arousal during the daily
      experience of self-focused thinking. The present study investigates the
      association between self-focus and autonomic activity using the experience
      sampling method with ambulatory monitoring of heart rate variability (HRV). Forty
      five students reported the content of their thoughts during their daily
      activities while their heart rate (HR) was being recorded. Multilevel modeling
      analyses showed that HRV was lower (and HR was higher) over the sampling day if
      participants engaged in more self-focus, while HRV increased (and HR decreased)
      from midday to nighttime if participants did not engage in self-focused thinking.
      These results suggest that self-focus at night is associated with increased
      physiological arousal, and leads to inhibition of de-arousal associated with
      normal sleep processes. Implications for insomnia are discussed. 

PMID- 24444703
TI  - Effectiveness and cost-effectiveness of different immunization strategies against
      whooping cough to reduce child morbidity and mortality.
AB  - INTRODUCTION: In the last years there has been a significant increase in reported
      cases of pertussis in developed countries, in spite of high rates of childhood
      immunization. Health institutions have recommended different vaccination
      strategies to reduce child morbidity and mortality: vaccination of adolescents
      and adults, pregnant women, people in contact with the newborn (cocoon strategy)
      and health care workers. The aim of this paper is to review the scientific
      evidence supporting these recommendations. METHODS: Systematic review on the
      effectiveness and cost-effectiveness of the above strategies for the reduction of
      morbidity and mortality from pertussis in infants under 12 months. The electronic
      databases Medline, PreMedline, Embase, CRD, Cochrane Central, and Trip Database
      were consulted from 1990 to October 2012. The evidence was assessed using the
      GRADE system. RESULTS: There were eight studies on the efficacy or safety of the
      strategies analyzed, and 18 economic evaluations. Direct evidence on the efficacy
      of these strategies is scarce. Economic evaluations suggest that vaccination of
      adolescents and adults would be cost-effective, although there is major
      uncertainty over the parameters used. CONCLUSIONS: From the perspective of health
      technology assessment, there is insufficient evidence to recommend the
      vaccination strategies evaluated.

PMID- 24444704
TI  - Perineal retraining improves conservative treatment for faecal incontinence: a
      multicentre randomized study.
AB  - BACKGROUND: Anal incontinence is a frequent complaint that profoundly affects
      quality of life. Our aim was to determine whether perineal retraining gives
      additional benefits to standard medical treatment. METHODS: Patients with anal
      incontinence and a Wexner score >4 were randomly assigned to standard
      conservative treatment (control) or perineal retraining, including biofeedback,
      in addition to standard treatments (biofeedback). Diaries, self-administered
      questionnaires and satisfaction scores quantified the benefits. Self-evaluated
      improvement was the primary outcome measure. A score >=3 (in an improvement scale
      from -5 to +5) defined success. RESULTS: Overall, 157 patients were included; 80
      in the control group (75% females, mean age 60.1 +/- 13.2 years) and 77 in the
      biofeedback group (79% females, mean age 61.9 +/- 10.2 years). After a 4-month
      follow-up, the success rate was significantly higher in the biofeedback group
      (57% versus 37%; p<0.021). In the biofeedback group, daily stool frequency,
      leakage, and faecal urgency significantly decreased, and daily non-urgent
      perception of stool increased. Conversely, symptomatic scores and quality of life
      scales did not significantly differ between groups. In a multivariate model, the
      adjusted odds ratio showed that perineal retraining was significantly associated
      with a higher chance of self-rated improvement (adjusted Odd Ratio [95%CI]: 2.34
      [1.14-4.80]; p=0.021). CONCLUSIONS: Perineal retraining offers a moderate but
      significant benefit for patients suffering from anal incontinence.

PMID- 24444706
TI  - Improved system identification with Renormalization Group.
AB  - This paper proposes an improved system identification method with Renormalization
      Group. Renormalization Group is applied to a fine data set to obtain a coarse
      data set. The least squares algorithm is performed on the coarse data set. The
      theoretical analysis under certain conditions shows that the parameter estimation
      error could be reduced. The proposed method is illustrated with examples. 

PMID- 24444705
TI  - Analysis of heavy and light chain sequences of conventional camelid antibodies
      from Camelus dromedarius and Camelus bactrianus species.
AB  - Camel antibodies have been widely investigated, but work has focused upon the
      unique heavy chain antibodies found across camelid species. These are homodimers,
      devoid of light chains and the first constant heavy chain domain. Camelid species
      also display conventional hetero-tetrameric antibodies with identical pairs of
      heavy and light chains; in Camelus dromedarius these constitute 25% of
      circulating antibodies. Few investigations have been made on this subset of
      antibodies and complete conventional camel IgG sequences have not been reported.
      Here we study the sequence diversity of functional variable and constant regions
      observed in 57 conventional heavy, 18 kappa and 35 lambda light chains of C.
      dromedarius and Camelus bactrianus. We detail sequences of the full kappa and
      lambda light chain, variable and CH1 region for IgG1a and IgG1b and the CH2 and
      CH3 region for IgG1a. The majority (60%) of IgG1 variable region sequences
      aligned with the human IgHV3 family (clan III) and had leader sequences beginning
      with MELG whereas the remaining sequences aligned with the IgHV4 (clan II) and
      had leader sequences beginning with MRLL. Distinct differences in CDR length were
      observed between the two; where CDR1 was typically 5 and 7 residues and CDR2 at
      17 and 16 residues, respectively. CDR3 length of IgHV4 (range 11 to 20) was
      closer to that typical of VHH antibodies than that of IgHV3 (range 3 to 18
      residues). Designed oligonucleotide primers have enabled identification of paired
      heavy and light chains of conventional camel antibodies from individual B cell
      clones. 

PMID- 24444707
TI  - A strategy to optimize CT use in children with mild blunt head trauma utilizing
      clinical risk stratification; could we improve CT use in children with mild head
      injury?
AB  - AIM: The purpose of our study was to investigate the impact of clinical risk
      classification on optimization of the rationale of CT scanning in children with
      mild blunt head trauma. Exposed effective radiation dose values of CT scanning
      were also evaluated. METHODS: Children with isolated pediatric mild head trauma
      admitted in a single center over a 5-year period (n=3102, >2 years and <16 years
      of age) were retrospectively reviewed. The study group comprised 806 patients
      with a mean age of 7.4+/-2.1 years (range, 2-15 years). The patients were
      categorized into low and high risk groups with regard to presence of predefined
      signs and symptoms. Effective radiation dose values were calculated. RESULTS:
      Incidences of the pathologic CT findings related to trauma were significantly
      different between low (n=10) 1.9% and high (n=90) 29.8% risk groups. Certain
      predefined signs and symptoms (e.g., vomiting, suspected skull fracture and loss
      of consciousness) were related significantly with pathologic CT findings
      attributed to trauma. Estimated mean effective dose values were 3.91+/-0.38mSv
      for 2-6 year old (n=557), and 3.33+/-0.12mSv for 7-16 year old patients (n=349).
      CONCLUSION: The pediatric victims of mild head trauma patients within high risk
      group and those with vomiting, suspected skull fracture and loss of consciousness
      should undergo head CT scanning. The manufacturer settings on the CT scanners for
      children should be revised to alleviate untoward radiation exposure.

PMID- 24444708
TI  - Sellar collision tumor involving metastatic lung cancer and pituitary adenoma:
      radiologic-pathologic correlation and review of the literature.
AB  - Collision tumors of the sella turcica involving metastases to pituitary adenomas
      are rare. We report a case of a collision tumor involving metastatic lung cancer
      with an emphasis on the neuroimaging and histopathological studies. A review of
      the literature including the diagnostic and management implications as well as
      pathogenetic mechanisms is also discussed. 

PMID- 24444710
TI  - Glycinamide ribonucleotide formyl transferase is frequently overexpressed in
      glioma and critically regulates the proliferation of glioma cells.
AB  - AIMS: Current treatments for the most common form of brain tumor, glioma, are
      disappointing in their effectiveness. Low expression levels of GART, an enzyme in
      the core nucleotide metabolism, significantly correlate with chemosensitivity,
      conferring a survival advantage to tumor cells. Our study aimed to explore the
      expression and function of GART in glioma. METHODS: Immunohistochemical and
      Western blot analysis were performed in 70 cases of human gliomas and normal
      brain tissues. We mainly used cell growth assay and multicellular tumor spheroid
      formation assay to evaluate the proliferation and chemosensitivity of glioma
      cells. RESULTS: High GART expression (most cancer cells cytoplasm stained) was
      observed in 70 specimens and was related to the grade of malignancy. We also
      reviewed each grade of tumors separately and investigated whether GART expression
      predicted patient survival within each subgroup. In brief, GART overexpression
      was significantly associated with overall survival (P=0.03). Interestingly,
      transfecting cells with GART-siRNA suppressed proliferation and enhanced
      temozolomide (TMZ)-induced apoptosis in glioma cells. CONCLUSION: The current
      results showed that GART expression was associated with glioma grade and that
      high GART protein expression might be related to poor outcome.

PMID- 24444709
TI  - A new non-canonical pathway of Galpha(q) protein regulating mitochondrial
      dynamics and bioenergetics.
AB  - Contrary to previous assumptions, G proteins do not permanently reside on the
      plasma membrane, but are constantly monitoring the cytoplasmic surfaces of the
      plasma membrane and endomembranes. Here, we report that the Galphaq and Galpha11
      proteins locate at the mitochondria and play a role in a complex signaling
      pathway that regulates mitochondrial dynamics. Our results provide evidence for
      the presence of the heteromeric G protein (Galphaq/11betagamma) at the outer
      mitochondrial membrane and for Galphaq at the inner membrane. Both localizations
      are necessary to maintain the proper equilibrium between fusion and fission;
      which is achieved by altering the activity of mitofusin proteins, Drp1, OPA1 and
      the membrane potential at both the outer and inner mitochondrial membranes. As a
      result of the absence of Galphaq/11, there is a decrease in mitochondrial fusion
      rates and a decrease in overall respiratory capacity, ATP production and OXPHOS
      dependent growth. These findings demonstrate that the presence of Galphaq
      proteins at the mitochondria serves as a physiological function: stabilizing
      elongated mitochondria and regulating energy production in Drp1 and Opa1
      dependent mechanisms. This thereby links organelle dynamics and physiology. 

PMID- 24444713
TI  - Dynamics of infectious diseases.
AB  - Modern infectious disease epidemiology has a strong history of using mathematics
      both for prediction and to gain a deeper understanding. However the study of
      infectious diseases is a highly interdisciplinary subject requiring insights from
      multiple disciplines, in particular a biological knowledge of the pathogen, a
      statistical description of the available data and a mathematical framework for
      prediction. Here we begin with the basic building blocks of infectious disease
      epidemiology--the SIS and SIR type models--before considering the progress that
      has been made over the recent decades and the challenges that lie ahead.
      Throughout we focus on the understanding that can be developed from relatively
      simple models, although accurate prediction will inevitably require far greater
      complexity beyond the scope of this review. In particular, we focus on three
      critical aspects of infectious disease models that we feel fundamentally shape
      their dynamics: heterogeneously structured populations, stochasticity and spatial
      structure. Throughout we relate the mathematical models and their results to a
      variety of real-world problems.

PMID- 24444714
TI  - Electrochemical characterization of liquid phase exfoliated two-dimensional
      layers of molybdenum disulfide.
AB  - We report on the electrochemical charge storage behavior of few-layered flakes of
      molybdenum disulfide (MoS2) obtained by liquid phase exfoliation of bulk MoS2
      powder in 1-dodecyl-2-pyrrolidinone. The specific capacitances of the exfoliated
      flakes obtained using a 6 M KOH aqueous solution as an electrolyte were found to
      be an order of magnitude higher than those of bulk MoS2 (~0.5 and ~2 mF cm(-2)
      for bulk and exfoliated MoS2 electrodes, respectively). The exfoliated MoS2
      flakes also showed significant charge storage in different electrolytes, such as
      organic solvents [1 M tetraethylammonium tetrafluoroborate in propylene carbonate
      (Et4NBF4 in PC)] and ionic liquids [1-butyl-3-methylimidazolium
      hexafluorophosphate (BMIM-PF6)]. The values of specific capacitances obtained
      using Et4NBF4 in PC and BMIM-PF6 were ~2.25 and ~2.4 mF cm(-2), respectively. An
      analysis of electrochemical impedance spectroscopy using an equivalent circuit
      modeling was performed to understand the charge storage mechanism of these
      exfoliated MoS2 flakes using different electrolytes. Our findings indicate that
      liquid phase exfoliation methods can be used to produce large quantities of
      electrochemically active, two-dimensional layers of MoS2 and can act as an ideal
      material in several applications related to electrochemistry. 

PMID- 24444711
TI  - Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine
      circuit.
AB  - Although the roles of mitogen-activated protein kinase (MAPK) and
      phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well
      established, KRAS activates additional pathways required for tumor maintenance,
      the inhibition of which are likely to be necessary for effective KRAS-directed
      therapy. Here, we show that the IkappaB kinase (IKK)-related kinases Tank-binding
      kinase-1 (TBK1) and IKKepsilon promote KRAS-driven tumorigenesis by regulating
      autocrine CCL5 and interleukin (IL)-6 and identify CYT387 as a potent
      JAK/TBK1/IKKepsilon inhibitor. CYT387 treatment ablates RAS-associated cytokine
      signaling and impairs Kras-driven murine lung cancer growth. Combined CYT387
      treatment and MAPK pathway inhibition induces regression of aggressive murine
      lung adenocarcinomas driven by Kras mutation and p53 loss. These observations
      reveal that TBK1/IKKepsilon promote tumor survival by activating CCL5 and IL-6
      and identify concurrent inhibition of TBK1/IKKepsilon, Janus-activated kinase
      (JAK), and MEK signaling as an effective approach to inhibit the actions of
      oncogenic KRAS. 

PMID- 24444712
TI  - RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy,
      reveals myc as a driver of Pten-mutant metastasis.
AB  - Genetically engineered mouse (GEM) models are a pillar of functional cancer
      research. Here, we developed RapidCaP, a GEM modeling system that uses surgical
      injection for viral gene delivery to the prostate. We show that in Pten
      deficiency, loss of p53 suffices to trigger metastasis to distant sites at
      greater than 50% penetrance by four months, consistent with results from human
      prostate cancer genome analysis. Live bioluminescence tracking showed that
      endogenous primary and metastatic disease responds to castration before
      developing lethal castration resistance. To our surprise, the resulting lesions
      showed no activation of Akt but activation of the Myc oncogene. Using RapidCaP,
      we find that Myc drives local prostate metastasis and is critical for maintenance
      of metastasis, as shown by using the Brd4 inhibitor JQ1. Taken together, our data
      suggest that a "MYC-switch" away from AKT forms a critical and druggable event in
      PTEN-mutant prostate cancer metastasis and castration resistance. 

PMID- 24444715
TI  - Sexual maturation, serum steroid concentrations, and mRNA expression of IGF-1,
      luteinizing and progesterone hormone receptors and survivin gene in Japanese
      quail hens.
AB  - In avian species, sexual maturation represents the evidence of start laying,
      which is a consequence of the development of ovarian follicles. These follicles
      are the functional reproductive unit whose maturation and viability critically
      depends on endocrine, paracrine, and autocrine factors beyond the signals from
      the central nervous system. The present study was undertaken to investigate the
      correlation of sexual maturity with tissue growth, mRNA expression of certain
      genes, and serum steroid concentrations in Japanese quail hens. To carry out the
      present study, a total of forty Japanese quail hens (5 weeks) were housed
      individually under uniform husbandry condition with ad libitum quail layer ration
      and water at 14-hour photo schedule. On sixth week onwards, four birds were
      sacrificed at each time on 1, 3, 7, 10, 13, 16, 19, 22, 25, and 28 days. Serum
      was extracted aseptically to analyze the gonadal steroid hormones (estrogen and
      progesterone) and corticosterone to investigate the liaison with sexual
      maturation of the species. Expression analyses of four genes i.e., insulin-like
      growth factor-1, luteinizing hormone receptor, progesterone receptor, and
      survivin were carried out in the three largest ovarian yellow follicles. A
      significant (P < 0.05) increase in body weight gain and oviduct weight was
      recorded during the phase of sexual maturation. Smaller follicles revealed higher
      insulin-like growth factor-1 and survivin gene expression, whereas the reverse
      result was manifested in both the luteinizing and progesterone hormone receptors.
      In biochemical study, the gonadal steroids (estrogen and progesterone) were
      recorded higher at the first half of the experiment when a gradual decrease in
      corticosterone concentration was confirmed from the very beginning of this study.
      This result substantiated that sexual maturation in Japanese quail may be
      completed by the time of 8 weeks after its birth in support of the analyzed
      information studied in the current investigation. 

PMID- 24444716
TI  - The administration of Sheng Hua Tang immediately after delivery to reduce the
      incidence of retained placenta in Holstein dairy cows.
AB  - Sheng Hua Tang, a classical herbal formula consisting of Radix Angelicae
      sinensis, Ligustici rhizoma, Semen persicae, Zingiberis rhizoma, and Radix
      glycyrrhizae, is known to be beneficial in alleviating postpartum diseases and
      facilitating a return to normal reproductive function. This study investigated
      whether the administration of Sheng Hua Tang within 2 to 4 hours after delivery
      was effective as a preventive treatment for reducing the risk of retained
      placenta in Holstein dairy cows. A total of 357 cows, each of which had delivered
      its calf spontaneously, were randomly allocated to one of two groups. In the
      treatment group, the cows (n = 175) received Sheng Hua Tang with an oral dose of
      0.36 g crude herb per kg.body weight once daily for three consecutive days. The
      controls (n = 182) received no treatment. The placental retention proportion was
      4.0% and 17.0% within 12 hours after delivery in the treated and control animals,
      respectively (P < 0.01). We found decreases in the calving-to-first-service
      interval (73.2 +/- 25.1 vs. 81.9 +/- 32.8 days; P < 0.01), calving-to-conception
      interval (93.4 +/- 38.8 vs. 114.6 +/- 42.9 days; P < 0.01), and service per
      conception (1.5 +/- 0.8 vs. 1.9 +/- 1.0 days; P < 0.01) in the treatment group
      compared with the control group. The first artificial insemination conception
      proportion was higher in the treatment group than in the control group (60.4% vs.
      41.1%; P = 0.01). Moreover, the between-group difference in the proportion of
      cows that were pregnant within 180 days postpartum approached statistical
      significance (88.2% vs. 80.6%; P = 0.07). Sheng Hua Tang showed beneficial
      effects in reducing the incidence of retained placenta and improving subsequent
      reproductive performance in cows. This preventive treatment strategy would be
      effective in improving the management of puerperal health. The potential benefits
      of Sheng Hua Tang warrant further investigation to determine whether this
      preventive treatment strategy can be endorsed as a general preventive approach in
      postpartum cows. 

PMID- 24444717
TI  - Host-pathogen interactions in epidermolysis bullosa patients colonized with
      Staphylococcus aureus.
AB  - Patients with the genetic blistering disease epidermolysis bullosa (EB) often
      have chronic wounds that can become colonized by different bacteria, especially
      the opportunistic pathogen Staphylococcus aureus. We therefore determined the S.
      aureus colonization rates in EB patients from the Netherlands by collecting swabs
      from their anterior nares, throats and wounds. Within a period of ~2 years, more
      than 90% of the sampled chronic wounds of EB patients were found to be colonized
      by S. aureus. Molecular typing revealed that EB patients were not colonized by a
      single S. aureus type. Rather the S. aureus population structure in the sampled
      EB patients mirrored the local S. aureus population structure within the
      Netherlands. Furthermore, multiple types of S. aureus were found in close
      proximity to each other within individual chronic wounds, indicating that these
      S. aureus types are not mutually exclusive. Over time, strong fluctuations in the
      S. aureus types sampled from individual EB patients were observed. This high
      exposure to different S. aureus types is apparently reflected by high plasma
      levels of antistaphylococcal IgG's, especially in patients carrying multiple S.
      aureus types. It remains to be determined to what extent this strong immune
      response protects EB patients against serious staphylococcal infections. Lastly,
      further research is needed to define the impact of staphylococcal colonization of
      chronic wounds on the development, exacerbation and healing of such wounds in
      patients with EB. 

PMID- 24444718
TI  - Functional and structural analysis of the major amidase (Atl) in Staphylococcus.
AB  - The cytoplasmic membrane of most bacteria is surrounded by a more or less thick
      murein layer (peptidoglycan) that protects the protoplast from mechanical damage,
      osmotic rupture and lysis. When bacteria are dividing processes are initiated
      stepwise that involve DNA replication, constriction of the membranes, cell
      growth, biosynthesis of new murein, and finally the generation of two daughter
      cells. As the daughter cells are still covalently interlinked by the murein
      network they must be separated by specific peptidoglycan hydrolases, also
      referred to as autolysins. In staphylococci, the major autolysin (Atl) and its
      processed products N-acetylmuramoyl-l-alanine amidase (AM) and endo-beta-N
      acetylglucosaminidase (GL) have been in the research focus for long time. This
      review addresses phenotypic consequences of atl mutants, impact of Atl in
      virulence, the mechanism of targeting to the septum region, regulation of atl,
      the structure of the amidase and the repeat regions, as well as the phylogeny of
      Atl and its use in Staphylococcus genus and species typing. 

PMID- 24444719
TI  - Distribution of small native plasmids in Streptococcus pyogenes in India.
AB  - Complete characterization of a Streptococcus pyogenes population from a defined
      geographic region comprises information on the plasmids that circulate in these
      bacteria. Therefore, we determined the distribution of small plasmids (<5kb) in a
      collection of 279 S. pyogenes isolates from India, where diversity of strains and
      incidence rates of S. pyogenes infections are high. The collection comprised 77
      emm-types. For plasmid detection and discrimination, we developed PCRs for
      different plasmid replication initiation protein genes, the putative repressor
      gene copG and bacteriocin genes dysA and scnM57. Plasmid distribution was limited
      to 13 emm-types. Co-detection analysis using aforementioned PCRs revealed four
      distinct plasmid sub-types, two of which were previously unknown. Representative
      plasmids pA852 and pA996 of the two uncharacterized plasmid sub-types were
      sequenced. These two plasmids could be assigned to the pMV158 and the
      pC194/pUB110 family of rolling-circle plasmids, respectively. The majority of
      small plasmids found in India belonged to the two newly characterized sub-types,
      with pA852- and pA996-like plasmids amounting to 42% and 22% of all detected
      plasmids, respectively. None of the detected plasmids coded for a known
      antibiotic resistance gene. Instead, all of the four plasmid sub-types carried
      known or potential bacteriocin genes. These genes may have influence on the
      evolutionary success of certain S. pyogenes genotypes. Notably, pA852-like
      plasmids were found in all isolates of the most prevalent emm-type 11.0.
      Together, a priori fitness of this genotype and increased fitness due to the
      acquired plasmids may have rendered type emm11.0 successful and caused the
      prevalence of pA852-like plasmids in India. 

PMID- 24444720
TI  - Molecular detection of Pythium insidiosum from soil in Thai agricultural areas.
AB  - Pythium insidiosum is an aquatic fungus-like organism in the kingdom Stramenopila
      that causes pythiosis in both humans and animals. Human pythiosis occurs in
      ocular, localized granulomatous subcutaneous and systemic or vascular forms.
      Individuals whose occupations involve exposure to aquatic habitats have an
      elevated risk of contracting pythiosis. Previously, we reported the first
      successful isolation of Pythium insidiosum from aquatic environmental samples by
      culture including confirmation using molecular methods. In this study, we show
      that P. insidiosum inhabitats moist soil environments in agricultural areas. A
      total of 303 soil samples were collected from 25 irrigation sources in the areas
      nearby the recorded home addresses of pythiosis patients residing in northern
      provinces of Thailand. P. insidiosum DNA was identified directly from each soil
      extract by using a nested PCR assay and subsequent phylogenetic analysis of the
      ribosomal intragenic spacer region. P. insidiosum DNA could be detected from 16
      of the 25 soil sources (64%). Conventional culture methods were also performed,
      however all samples exhibited negative culture results. We conclude that both
      irrigation water and soil are the natural reservoirs of P. insidiosum. In endemic
      areas, the exposure to these environmental reservoirs should be considered a risk
      factor for hosts susceptible to pythiosis. 

PMID- 24444721
TI  - The study of NAD-malic enzyme in Amaranthus cruentus L. under drought.
AB  - Decarboxylating NAD-malate dehydrogenase (NAD-malic enzyme, NAD-ME, EC 1.1.1.39)
      has been investigated under a long-term drought during pre-anthesis, anthesis and
      seed-formation phases of ontogenesis of a NAD-ME type C4 plant Amaranthus
      cruentus L. using cytosol, chloroplast and mitochondrial fractions of mesophyll
      (M) and bundle sheath (BS) cells. We detected several molecular forms of NAD-ME
      with different subcellular localization patterns in the studied phases of
      amaranth ontogenesis. However, no enzyme activity was observed experimentally in
      chloroplasts of M and BS cells. In the pre-anthesis phase NAD-ME isoform with
      molecular weight of ~115 kDa was found in cytosol of M and BS cells of control
      and drought-exposed plants. One of NAD-ME isoforms with molecular weight of 110
      kDa was located in mitochondria of BS cells of control and drought-exposed
      plants, and a new isoform of ~121 kDa was formed in mitochondria of BS cells
      under the influence of drought. After resuming watering this isoform (~121 kDa)
      disappeared again. Approximately 90.6% and 9.4% of the total NAD-ME activity were
      localized in mitochondrial stroma and cytosol of BS cells, respectively, while in
      mesophyll cells 100% activity was found in cytosol fractions. The reaction
      catalyzed by NAD-ME follows Michaelis-Menten equation. NAD(+), l-malate and
      Mn(2+) activate this enzyme in mitochondria. Appearance of the ~121 kDa isoform
      of NAD-ME in the mitochondrial fraction of BS cells under drought and its
      disappearance after resuming watering could be attributed to one of the
      protection functions of plants. 

PMID- 24444722
TI  - A systematic review of the complex organization of human cognitive domains and
      their heritability.
AB  - BACKGROUND: Models of cognition propose a hierarchical structure for human
      cognitive processes, in which the sequences of human action are organized into
      parts or subunits of analysis that can be grouped into progressively more
      complex, inclusive higher-order functions. This organizational structure from
      partial to whole may be reflected in the neural representations that underlie
      human behaviour, and in its genetic underpinnings. The objective of the present
      study was to explore a putative hierarchical organization of the genetic
      influences underlying cognitive domains. METHOD: Thirty four studies of the
      heritability of cognition on population-based samples were reviewed, which
      included measures of intelligence, verbal and performance abilities, memory,
      working memory and processing speed. RESULTS: Specific cognitive domains showed
      diverse proportions of genetic underpinnings such that higher-order cognitive
      functions present high heritability estimates, whereas lower-order functions
      respond to small/moderate heritability estimates. CONCLUSIONS: Based on current
      understanding of the developmental processes of the neurobiological substrates of
      human cognition, the genetic contributions to cognitive abilities seem to be
      organized in line with the ontogenic maturation of the brain. We discuss the
      large genetic control of the combinatory capacity of basic cognitive functions,
      and its interaction with environmental influences.

PMID- 24444723
TI  - An experimental analysis of obsessive-compulsive checking as avoidance behaviour.
AB  - BACKGROUND: Many explanatory models of obsessive-compulsive disorders (OCD)
      support the idea that compulsive behaviours are an attempt to avoid an aversive
      situation. There are few experimental studies carried out on the onset of
      repetitive behaviours. This study tries to create a repetitive checking behaviour
      as an analogue explaining similar OCD behaviours. METHOD: An inter-group design
      with 3 levels of aversion (minimal, progressive and maximum) in a visuo-spatial
      reasoning task was used. 48 university students without OCD problems (mean= 23
      years old) were the participants, randomly distributed in 16 per group. Checking
      frequency (semi-hidden chronometer) for each task was measured and the
      questionnaires TONI-2, STAI, MOCI and YBOCS-SR were applied. RESULTS:
      Participants with a minimal or maximum level difficulty showed a significantly
      higher level of checking behaviour than those in the progressive difficulty. The
      differences occurred between the minimal and the progressive group, and between
      the minimal and maximum difficulty. There were no differences in any other
      variable. CONCLUSION: In this analogue, the continuous checking of a chronometer
      was reinforced by the elimination of boring tasks. The momentary escape from an
      aversive situation explains the checking behaviour. This study could be an
      experimental analogue of checking behaviour, showing its avoidance function.

PMID- 24444724
TI  - Language laterality, handedness and empathy in a sample of parents of children
      with autism spectrum disorder.
AB  - BACKGROUND: First-order relatives of persons with Autism Spectrum Disorder (ASD)
      exhibit a cognitive pattern which is part of a broader autism phenotype. METHOD:
      The purpose of the present study was to evaluate whether some neuropsychological
      features related to the autism phenotype are present in parents of ASD children.
      To this end, the exploration included a dichotic listening task, handedness and
      the Empathy Quotient (EQ-60). RESULTS: The scores obtained by the total sample
      (fathers plus mothers) were similar to those of the general population, although
      there were differences in some parameters of the dichotic listening task
      depending on the gender. Contrary to expectations, only in fathers, the negative
      correlation between data from both ears was not statistically significant, which
      could be evidence of a lack of hemispheric interdependence. CONCLUSIONS: These
      results support the possible existence of a genetic susceptibility to an aberrant
      language asymmetry pattern. Moreover, possible unknown epigenetic factors could
      act on a vulnerable genotype in some ASD subjects. Nevertheless, due to the small
      sample size, the present research must be considered a pilot study.

PMID- 24444725
TI  - Evaluation and early detection of problematic Internet use in adolescents.
AB  - BACKGROUND: Problematic Internet use in adolescents has become an issue of
      concern for a growing number of researchers and institutions over the past years.
      Behavioural problems, social isolation, school failure and family problems are
      some of the consequences of psychological and behavioural impact on teenagers.
      Taking into account the interest that this issue has generated at many levels,
      the aim of this paper is to develop a screening tool for early detection of
      problematic Internet use in teenagers. METHOD: A survey of Compulsory Secondary
      School students from Galicia involving a total of 2,339 individuals was carried
      out. RESULTS: The results obtained allow (1) gauging the magnitude of the
      problem, establishing the risk levels among the adolescents, and (2) presenting a
      new, simple and short screening instrument. CONCLUSIONS: The present scale has
      sufficient theoretical and empirical support, including good psychometric
      properties (a = .83; specificity = .81; sensitivity = .80; ROC curve = .90),
      making it an interesting applied tool.

PMID- 24444726
TI  - Comorbidity of oppositional defiant disorder and anxiety disorders in
      preschoolers.
AB  - BACKGROUND: The aim was to study the comorbidity of oppositional defiant disorder
      (ODD) and anxiety disorders (AD) among preschool children of the general
      population, and to assess the contribution of comorbidity to the child's
      functional impairment. METHOD: 622 children were assessed at the ages of 3 and 5,
      through a diagnostic interview. They were clustered into three diagnostic groups:
      only ODD, only AD and comorbid ODD+AD. RESULTS: At age 3, ODD was associated with
      specific phobia, OR = 4.7, 95% CI [1.4, 14.1], and at age 5, with any anxiety
      disorder, OR=3.9; 95% CI [1.8, 8.4]. ODD at age 3 was predictive of separation
      anxiety at age 5, OR=4.1; 95% CI [1.2, 14.3]. Comorbid ODD+AD cases showed a
      higher risk of functional impairment at school and in behavior toward others. Sex
      and socioeconomic status were not related to the diagnostic group. CONCLUSIONS:
      ODD+AD comorbidity can be identified in preschool children. Early identification
      of this association is needed to adequately treat the affected children.

PMID- 24444727
TI  - Comparing intergroup contact effects on blatant and subtle prejudice in
      adolescents: a multivariate multilevel model.
AB  - BACKGROUND: The literature has rarely paid attention to the differential
      influence of intergroup contact on subtle and blatant prejudice. In this study,
      we hypothesized that the influence of intergroup contact on subtle prejudice will
      be smaller than its influence on blatant prejudice. METHOD: This hypothesis was
      tested with data from a cross-sectional design on 1,655 school-aged native
      Spanish adolescents. Prejudice was measured with a shortened version of the
      Meertens and Pettigrew scale of blatant and subtle prejudice adapted to Spanish
      adolescent population. RESULTS: Results from multivariate multilevel analyses for
      correlated outcome variables supported the hypothesis. Students tended to score
      higher on the subtle prejudice scale; contact with the outgroup was statistically
      related both to levels of blatant and subtle prejudice; and, the negative
      relationship of contact with the outgroup and prejudice is greater for blatant
      prejudice as compared to subtle prejudice. CONCLUSIONS: Overall, results provide
      statistical evidence supporting the greater resistance to change of subtle forms
      of prejudice.

PMID- 24444728
TI  - Psychometric properties of the AQ Aggression Scale in Chilean students.
AB  - BACKGROUND: The Buss and Perry Aggression Questionnaire (AQ) evaluates aggressive
      behaviours and is used to assess manifestations of aggression. METHODS: At
      different points in time, 346 Chilean university students participated in the
      validation of the instrument, whose convergent validity was shown in relation to
      the scales of Psychological Aggression and Physical Aggression of the Conflict
      Tactics Scale 2 (CTS- 2), and the Salvo Impulsivity Scale. Discriminant validity
      was found when comparing the scores obtained from a group of students categorized
      as "Violent" with those of a control group, after a screening test. RESULTS: The
      AQ scale has appropriate psychometric properties in terms of internal
      consistency, test-retest reliability, convergent validity and discriminant
      validity. Four principal factors were obtained in the confirmatory factor
      analysis. CONCLUSIONS: The AQ can be used in Chile to assess aggressive
      behaviours. Challenges for future research are discussed.

PMID- 24444729
TI  - Psychometric characteristics of the BRIEF scale for the assessment of executive
      functions in Spanish clinical population.
AB  - BACKGROUND: The Behavior Rating Inventory of Executive Functions (BRIEF) scale,
      completed by families, is widely known in the assessment of executive functions
      in children and adolescents. However, its application is limited to English
      speaking population. METHOD: This study analyzes the preliminary results from its
      application in a Spanish clinical sample, comprising 125 participants aged 5-18
      years. Internal structure and reliability of the translated scale were analyzed,
      as well as its relationship with other behavioral measures through the analysis
      of their correlations with the Assessment of Attention Deficit Hyperactivity
      Disorder Scale (EDAH). The results were compared with those from the original
      validation study. RESULTS: The data revealed the presence of the same internal
      structure, as well as acceptable internal consistency and significant
      correlations with the Attention Deficit and Hyperactivity components of the EDAH
      scale. CONCLUSIONS: This study provides preliminary evidence of the utility of
      the BRIEF scale in cultural contexts different from the original, particularly in
      Spanish clinical population.

PMID- 24444730
TI  - Spanish adaptation of the Creative Potential and Practised Creativity scale (CPPC
      17) in the workplace and inside the organization.
AB  - BACKGROUND: This study follows the theoretical framework put forward by Hinton on
      creative potential and practised creativity. The objective was to adapt the 17
      item Creative Potential and Practised Creativity scale into Spanish and examine
      its psychometric properties. METHOD: The study sample was made up of 975 Spanish
      employees (48.5% men and 51.5% women). RESULTS: After performing a confirmatory
      factor analysis, the findings revealed a three-factor structure: Creative
      potential, Practised creativity and Perception of organizational support.
      Furthermore, appropriate reliability was found for all three factors as well as
      initial evidence of construct validity in relation to certain external correlates
      and a series of scales measuring workaholism, irritation, burnout and
      personality. CONCLUSIONS: The present scale may prove ideal for adequately
      identifying Creative potential, Practised creativity and Perceived organizational
      support.

PMID- 24444731
TI  - The Spanish version of the Work-related Acceptance and Action Questionnaire
      (WAAQ).
AB  - BACKGROUND: Psychological flexibility, a key construct of Acceptance and
      Commitment Therapy (ACT), has recently been found to be an important determinant
      of mental health and behavioral effectiveness in the workplace. This finding has
      led to designing a measure of psychological flexibility especially tailored to
      the workplace (the Work-related Acceptance and Action Questionnaire; WAAQ) in the
      hope that it may reveal even stronger associations with variables related to a
      work context. METHOD: First, we back-translated the WAAQ into Spanish and then
      administered it to 209 workers, in addition to other relevant work-related
      measures. RESULTS: Data were very similar to those obtained with the original
      WAAQ version. The WAAQ showed a very good internal consistency (a = .92) and a
      clear one-factor structure. It also showed higher correlations with work-specific
      measures than a general measure of psychological inflexibility (the Acceptance
      and Action Questionnaire-II; AAQ-II). As hypothesized by the ACT theory, the
      correlation between the WAAQ and the AAQ-II was moderate but not so high as to
      suggest that they are assessing the same construct. CONCLUSIONS: This Spanish
      translation of the WAAQ emerges as a reliable and valid measure of psychological
      flexibility in relation to the workplace.

PMID- 24444732
TI  - Followers' agreeableness and extraversion and their loyalty towards authentic
      leadership.
AB  - BACKGROUND: Effective leaders understand that loyal followers are the key for
      success. To win their loyalty, leaders usually build social exchange
      relationships with them, through a wide range of behaviours, such as honouring
      agreements or using open and transparent communication. However, the effect of
      these behaviours on their followers' loyalty can differ depending on followers'
      individual differences, especially in relational traits such as agreeableness and
      extraversion. METHOD: We explored the moderating role of followers' agreeableness
      and extraversion in the relationship between authentic leadership (using
      transactional leadership as reference group) and followers' loyalty. A two-wave
      experiment, where 224 participants with and without work experience were randomly
      assigned to either a transactional or authentic leadership style condition was
      conducted. RESULTS: Our results show that followers in the authentic leadership
      condition had higher levels of loyalty toward their leader. Moreover, followers'
      agreeableness played a negative moderating role in this relationship whereas
      extraversion played a positive moderating role in it. CONCLUSIONS: Our results
      indicate that followers' characteristics influence the effect of situational
      factors on their attitudes, such as loyalty, providing support for the need of a
      more integrative approach to leadership, where followers need to be considered as
      active elements of this process ofinfluence.

PMID- 24444733
TI  - Assessment of dispositional and contextual variables in educational settings:
      IEPA and AYES scales.
AB  - BACKGROUND: Despite the fact that there are a few instruments designed to measure
      dispositional and contextual variables in educational contexts, the goal of this
      study is to elaborate and validate two questionnaires to measure learning
      interest, effort and progression as dispositional (IEPA) and contextual (AYEs)
      variables in secondary education students. METHOD: An initial version of both
      scales was developed. They were reviewed by a panel of experts and tested on two
      pilot studies. The final versions were administered to the described sample and
      their psychometric properties were tested. Factor analyses (exploratory and
      confirmatory) were conducted on three sets of data: Mathematics (n = 290),
      Spanish Language and Literature (n = 283), and Physical Education (n = 289).
      RESULTS: Both final scales had three dimensions with four items in each
      dimension. All standardized loads and critical values of t were overwhelmingly
      positive, while alpha coefficients ranged from .85 to .91. Both scales showed
      adequate construct validity, convergent validity, discriminant validity and
      concurrent validity. CONCLUSIONS: Results showed that these new scales have
      adequate psychometric properties, allowing a valid and reliable assessment.

PMID- 24444734
TI  - An explanatory model of the intention to continue studying among non-traditional
      university students.
AB  - BACKGROUND: Although academic achievement is believed to be an important factor
      in students' decision to continue studying at university, research on this topic
      is limited. METHOD: The current study analyzed the relationship between academic
      achievement and the intention of 327 non-traditional students to continue
      studying at university, using a path model. RESULTS: The central hypothesis of
      the study was confirmed, as the intention to continue studying was determined by
      previous academic results, although the amount of variance explained was
      relatively low (13%). CONCLUSIONS: The results from this study indicate that the
      intention to continue studying at university depends less than expected on the
      performance achieved. So, universities should consider other variables such as
      the quality of the academic support offered to these students continue their
      studies.

PMID- 24444735
TI  - Methodological convergence of program evaluation designs.
AB  - BACKGROUND: Nowadays, the confronting dichotomous view between experimental/quasi
      experimental and non-experimental/ethnographic studies still exists but, despite
      the extensive use of non-experimental/ethnographic studies, the most systematic
      work on methodological quality has been developed based on experimental and quasi
      experimental studies. This hinders evaluators and planners' practice of empirical
      program evaluation, a sphere in which the distinction between types of study is
      changing continually and is less clear. METHOD: Based on the classical validity
      framework of experimental/quasi-experimental studies, we carry out a review of
      the literature in order to analyze the convergence of design elements in
      methodological quality in primary studies in systematic reviews and ethnographic
      research. RESULTS: We specify the relevant design elements that should be taken
      into account in order to improve validity and generalization in program
      evaluation practice in different methodologies from a practical methodological
      and complementary view. CONCLUSIONS: We recommend ways to improve design elements
      so as to enhance validity and generalization in program evaluation practice.

PMID- 24444736
TI  - Validating assessments: Introduction to the Special Section.
AB  - BACKGROUND: Validation is the process of providing evidence that tests and
      questionnaires are adequately and appropriately fulfilling the purposes for which
      they are developed. In this special issue, experts from several countries
      describe specific approaches to test validation and provide examples of their
      approach. These approaches and examples illustrate the validation framework
      implied by the Standards for Educational and Psychological Testing. METHOD: We
      describe the Standards' approach for building a validity argument based on
      validity evidence based on test content, response processes, internal structure,
      relations to other variables, and testing consequences. RESULTS: The five
      articles provide comprehensive examples of gathering data regarding these five
      sources of evidence and how they contribute to the validation of the use of test
      scores for particular purposes. CONCLUSIONS: These five articles provide concrete
      examples of how the five sources of validity evidence suggested by the Standards
      can be used to develop a sound validity argument to support the use of a test for
      its intended purposes.

PMID- 24444737
TI  - Validity evidence based on test content.
AB  - BACKGROUND: Validity evidence based on test content is one of the five forms of
      validity evidence stipulated in the Standards for Educational and Psychological
      Testing developed by the American Educational Research Association, American
      Psychological Association, and National Council on Measurement in Education. In
      this paper, we describe the logic and theory underlying such evidence and
      describe traditional and modern methods for gathering and analyzing content
      validity data. METHOD: A comprehensive review of the literature and of the
      aforementioned Standards is presented. RESULTS: For educational tests and other
      assessments targeting knowledge and skill possessed by examinees, validity
      evidence based on test content is necessary for building a validity argument to
      support the use of a test for a particular purpose. CONCLUSIONS: By following the
      methods described in this article, practitioners have a wide arsenal of tools
      available for determining how well the content of an assessment is congruent with
      and appropriate for the specific testing purposes.

PMID- 24444738
TI  - Validity evidence based on internal structure.
AB  - BACKGROUND: Validity evidence based on the internal structure of an assessment is
      one of the five forms of validity evidence stipulated in the Standards for
      Educational and Psychological Testing of the American Educational Research
      Association, American Psychological Association, and National Council on
      Measurement in Education. In this paper, we describe the concepts underlying
      internal structure and the statistical methods for gathering and analyzing
      internal structure. METHOD: An in-depth description of the traditional and modern
      techniques for evaluating the internal structure of an assessment. RESULTS:
      Validity evidence based on the internal structure of an assessment is necessary
      for building a validity argument to support the use of a test for a particular
      purpose. CONCLUSIONS: The methods described in this paper provide practitioners
      with a variety of tools for assessing dimensionality, measurement invariance and
      reliability for an educational test or other types of assessment.

PMID- 24444739
TI  - Demonstrating the validity of three general scores of PET in predicting higher
      education achievement in Israel.
AB  - BACKGROUND: The Psychometric Entrance Test (PET), used for admission to higher
      education in Israel together with the Matriculation (Bagrut), had in the past one
      general (total) score in which the weights for its domains: Verbal, Quantitative
      and English, were 2:2:1, respectively. In 2011, two additional total scores were
      introduced, with different weights for the Verbal and the Quantitative domains.
      This study compares the predictive validity of the three general scores of PET,
      and demonstrates validity in terms of utility. METHOD:  SAMPLE: 100,863 freshmen
      students of all Israeli universities over the classes of 2005-2009. Regression
      weights and correlations of the predictors with FYGPA were computed. Simulations
      based on these results supplied the utility estimates. RESULTS: On average, PET
      is slightly more predictive than the Bagrut; using them both yields a better tool
      than either of them alone. Assigning differential weights to the components in
      the respective schools further improves the validity. CONCLUSION: The
      introduction of the new general scores of PET is validated by gathering and
      analyzing evidence based on relations of test scores to other variables. The
      utility of using the test can be demonstrated in ways different from
      correlations.

PMID- 24444740
TI  - Validity evidence based on testing consequences.
AB  - BACKGROUND: Large-scale educational assessments in the U.S. are used as policy
      tools for improving instruction and evaluating educational programs and the
      effectiveness of educators. Because of the high-stakes nature of their use, it is
      imperative that validity evidence based on testing consequences is obtained to
      support their multiple purposes. METHOD: A comprehensive review of the literature
      related to validity evidence for test use was conducted. RESULTS: A theory of
      action for a testing program should be delineated. A theory of action reflects an
      interpretative and use argument and a validity argument for assessment programs
      and delineates the purposes and uses of the system as well as the outcomes of the
      system. The articulation of a validity argument allows for the accumulation of
      evidence not only for, but also against, intended score interpretations and uses.
      CONCLUSIONS: As described in the paper, for assessment and accountability systems
      that are intended to have an effect on both instruction and student learning, the
      consequences, both positive and negative, of the systems need to be evaluated.

PMID- 24444741
TI  - Validity evidence based on response processes.
AB  - BACKGROUND: Validity evidence based on response processes was first introduced
      explicitly as a source of validity evidence in the latest edition of Standards
      for Educational and Psychological Testing. In this paper, we present the theory,
      the relationship with other sources of validity evidence, and the methods
      available for validation studies aimed at obtaining validity evidence about
      response processes. METHOD: A comprehensive review of the literature along with
      theoretical and practical proposals. RESULTS: The articles provides arguments for
      determining when validity evidence based on response processes is critical for
      supporting the use of the test for a particular purpose, and examples of how to
      perform a validation study to obtain such validity evidence. CONCLUSIONS: There
      are methods for obtaining validity evidence based on response processes. Special
      attention should be paid to validation studies using the cognitive interview
      method given its features and possibilities. Future research problems pose how to
      combine data from different methods -qualitative and quantitative-, to develop
      complete validity arguments that support the use of the test for a particular
      purpose.

PMID- 24444742
TI  - Pediatric novice nurses: examining compassion fatigue as a mediator between
      stress exposure and compassion satisfaction, burnout, and job satisfaction.
AB  - We investigated whether compassion fatigue mediated associations between nurse
      stress exposure and job satisfaction, compassion satisfaction, and burnout,
      controlling for pre-existing stress. The Life Events Checklist was administered
      to 251 novice pediatric nurses at the start of the nurse residency program
      (baseline) and 3 months after to assess pre-existing and current stress exposure.
      Compassion satisfaction, compassion fatigue, and burnout were assessed 3 months
      after baseline and job satisfaction 6 months after. Stress exposure significantly
      predicted lower compassion satisfaction and more burnout. Compassion fatigue
      partially mediated these associations. Results demonstrate a need for hospitals
      to prevent compassion fatigue in healthcare providers. 

PMID- 24444743
TI  - Treatment of moderate to severe plaque psoriasis with biologics: analysis of the
      additional cost of temporary dose escalation vs switch to another biologic after
      failure of maintenance therapy.
AB  - INTRODUCTION: In the event of failure of maintenance therapy with biologic agents
      for moderate to severe plaque psoriasis, the possible approaches are to switch to
      another agent or escalate the dose (generally by increased dosing frequency).
      Knowledge of the economic impact of the 2 alternatives would be extremely useful
      for therapeutic decision making. OBJECTIVE: The present analysis aimed to
      determine the moment in which the annualized additional cost of escalation
      exceeds a specified cost overrun. MATERIALS AND METHODS: Based on the purchase
      cost (average wholesale price) of approved biologics for the treatment of
      moderate to severe psoriasis, the number of weeks of escalation of the initial
      biologic until the annualized cost of dose escalation ran ?1000 over the cost of
      switching to another biologic was calculated for a typical patient weighing 80
      kg. RESULTS: According to this model, switching to another biologic is always
      cost effective, with adalimumab followed by ustekinumab the best choices in this
      respect. Ustekinumab allows for a longer trial escalation period (2 to 4
      injections) before the cost overrun threshold is reached, whereas the threshold
      is reached in a single infusion if a patient is on infliximab. CONCLUSION: The
      study does not take into account the differential efficacy of the various
      biologic therapies as rescue treatment for failure of maintenance therapy given
      the lack of scientific evidence. The results nevertheless show substantial
      differences in the period during which treatment can be intensified before
      reaching the preset cost overrun.

PMID- 24444745
TI  - Flt3 signaling regulates the proliferation, survival, and maintenance of
      multipotent hematopoietic progenitors that generate B cell precursors.
AB  - Flt3 signaling plays a crucial role in regulating the survival and
      differentiation of lymphoid progenitors into B cell precursors (BCPs) in bone
      marrow. To define further the role of Flt3 signaling in lymphoid progenitor
      survival, mice deficient in Flt3 ligand that also expressed a Bcl2 transgene (EMU
      bcl2tg flt3l(-/-)) were generated. Intracellular flow cytometry established
      transgene expression in primitive hematopoietic progenitors, including lineage
      negative Sca-1(+) c-kit(+) (LSK(+)) CD27(-) cells enriched for functional
      hematopoietic stem cells. Compared with flt3l(-/-) mice, EMU-bcl2tg flt3l(-/-)
      mice had significantly increased multipotential progenitors (MPPs), IL-7R(+)
      common lymphoid progenitors, and B cell precursors. To determine whether forced
      expression of Bcl2 was sufficient to restore lymphoid priming in the absence of
      Flt3 signaling EMU-bcl2tg flt3l(-/-)rag1-gfp(+) mice were generated. Analysis of
      EMU-bcl2tg flt3l(-/-)rag1-gfp(+) mice revealed that the Bcl2 transgene had no
      effect on lymphoid priming before CD19 expression. Thus, forced expression of a
      survival gene can bypass the requirement for threshold levels of Flt3 signaling
      requisite for lymphoid priming. Temporal Flt3 ligand (FL) replacement therapy in
      flt3l(-/-) mice revealed specific requirements for Flt3 signaling in the
      expansion and maintenance of Flt3(+hi) MPP and Flt3(+) all lymphoid progenitors,
      but not Flt3(+) B lymphoid progenitors (BLPs), the immediate precursors of BCPs.
      BCPs were restored after temporal in vivo FL treatment, albeit with delayed
      kinetics. Together, these results show that Flt3 regulates the proliferation,
      survival, and maintenance of developmental stage-specific hematopoietic
      progenitors that give rise to BCPs.

PMID- 24444746
TI  - O-GlcNAc modification of tau directly inhibits its aggregation without perturbing
      the conformational properties of tau monomers.
AB  - The aggregation of the microtubule-associated protein tau into paired helical
      filaments to form neurofibrillary tangles constitutes one of the pathological
      hallmarks of Alzheimer's disease. Tau is post-translationally modified by the
      addition of N-acetyl-D-glucosamine O-linked to several serine and threonine
      residues (O-GlcNAc). Previously, increased O-GlcNAcylation of tau has been shown
      to block the accumulation of tau aggregates within a tauopathy mouse model. Here
      we show that O-GlcNAc modification of full-length human tau impairs the rate and
      extent of its heparin-induced aggregation without perturbing its activity toward
      microtubule polymerization. O-GlcNAcylation, however, does not impact the "global
      fold" of tau as measured by a Forster resonance energy transfer assay. Similarly,
      nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only
      minimally perturbs the local structural and dynamic features of a tau fragment
      (residues 353-408) spanning the last microtubule binding repeat to the major
      GlcNAc-acceptor Ser400. These data indicate that the inhibitory effects of O
      GlcNAc on tau aggregation may result from enhanced monomer solubility or the
      destabilization of fibrils or soluble aggregates, rather than by altering the
      conformational properties of the monomeric protein. This work further underscores
      the potential of targeting the O-GlcNAc pathway for potential Alzheimer's disease
      therapeutics.

PMID- 24444747
TI  - [Severe temporal bone fractures in children: clinical presentation, complications
      and sequelae observed in the last 11 years].
AB  - OBJECTIVES: To evaluate the clinical presentation, complications and sequelae in
      patients with temporal bone fracture in the last 11 years. MATERIAL AND METHODS:
      A total of 27 patient medical records were retrospectively analysed. RESULTS: Of
      the 27 patients who were admitted for temporal bone fracture from 2001 to 2012,
      13 (48%) had no petrous involvement (Group 1), and 14 (52%) with petrous
      involvement (Group 2). Patients in Group 2 had a longer P-ICU stay: median 4.5
      days (RI: 2.75-22.25 d) vs 2 (RI: 1-3 d) (P=.018); more days on mechanical
      ventilation support: median 3 days (RI: 1.50-17 d) vs 1 (RI: 1-1.25 d). This
      group also had a higher frequency in sequelae (P=.04 OR=1.4 (95% CI: 1.05-1.95))
      and a higher incidence in cerebrospinal fluid (CSF) fistula (P<.02; OR 2.33; 95%
      CI (1.27-4.27)). Severity scores (PRIMS III and PTI) showed no significant
      differences. Some degree of hearing loss was observed in 31% of the patients.
      Traffic accident was the main cause of trauma (33%), followed by falls (27%).
      There were 2 deaths and 4 (15%) had permanent sequelae. CONCLUSIONS: Isolated
      temporal bone fractures usually have a good outcome in children, but in some
      cases they can be fatal or have permanent sequelae. Long term follow up is
      recommended by authors.

PMID- 24444748
TI  - [Sepsis by Ewingella americana in an infant with congenital nephropathy].

PMID- 24444749
TI  - Language-dependent performance on the letter fluency task in patients with
      schizophrenia.
AB  - Two types of verbal fluency tasks (letter fluency task; LFT, category fluency
      task; CFT) have been widely used to assess cognitive function in people with
      psychiatric diseases including schizophrenia. The task demand of the LFT is
      considered to vary across languages, as the cognitive process largely relies on
      sound and writing systems. Specifically, a sound unit for a letter (s) and a
      manner of association between them are assumed to be related with the
      performance. In the current study, three analyses have been conducted to examine
      this issue, using Japanese, Turkish, and English-speaking patients with
      schizophrenia. It was hypothesized that severity of letter fluency impairment
      would be in the order of Japanese, Turkish, and English speaking patients
      according to the inflexibility of a word search. First, performance on the LFT
      and the CFT was compared among Japanese (N=40), Turkish (N=30), and the US (N=31)
      patients (Analysis 1). A significant difference was found between the US and
      other two groups only in the LFT. Second, verbal fluency performance was compared
      between Japanese and Turkish patients by contrasting the degree of
      disassociations from normal controls (Japanese: N=20, Turkish: N=30) (Analysis
      2). In Japanese patients, performance on the LFT was more severely impaired
      compared to that on the CFT while the opposite trend was found in the Turkish
      counterpart, suggesting that letter fluency performance was more degraded in
      Japanese patients. Finally, Analysis 3 was conducted to examine the relative
      order of letter fluency impairment among Japanese, Turkish and English-speaking
      patients. Disassociation in English users with schizophrenia was estimated based
      on previous meta-analytic reviews. The effect size (ES) for the letter fluency
      deficit was the largest in the Japanese sample, while the other two groups share
      similar ESs. The results from the three analyses partially supported the
      hypothesis for the severity of the letter fluency impairment in patients with
      schizophrenia. The language-dependency of letter fluency impairment was thought
      to be explained by the theoretical model built on unique properties of sound and
      writing systems. The considerations presented here would provide useful
      information for optimizing the portability of cognitive tasks across languages.

PMID- 24444750
TI  - How did national life expectation related to school years in developing countries
      - an approach using panel data mining.
AB  - BACKGROUND: The purpose of the study was to probe into the changes in life
      expectancy associated with schooling years found by the Organization for Economic
      Co-operation and Development (OECD). METHODS: The study was based on the OECD
      database from the period 2000 to 2006. The data of thirty countries were
      constructed to allow comparisons over time and across these countries. Panel data
      analysis was used to estimate the relationship of national education, as defined
      as school years, with life expectancy. The control factors considered were
      numbers of practicing physicians, practicing nurses, hospital beds, and GDP.
      RESULTS: We used fixed effects of both country and time through linear
      regression, the coefficient of school years in relation to life expectancy was
      statistically significant but negative. This finding is not in accord with the
      hypothesis that investing in human capital through education stimulates better
      health outcomes. CONCLUSION: Within developing countries, educational attainment
      is no longer keeping the same pace with life expectancy as before. Therefore, we
      suggest that an effective education policy should cover diverse topics, for
      example, balancing economic growth and mental hygiene, to improve national life
      expectancy.

PMID- 24444751
TI  - Hybridization between multi-objective genetic algorithm and support vector
      machine for feature selection in walker-assisted gait.
AB  - Walker devices are often prescribed incorrectly to patients, leading to the
      increase of dissatisfaction and occurrence of several problems, such as,
      discomfort and pain. Thus, it is necessary to objectively evaluate the effects
      that assisted gait can have on the gait patterns of walker users, comparatively
      to a non-assisted gait. A gait analysis, focusing on spatiotemporal and
      kinematics parameters, will be issued for this purpose. However, gait analysis
      yields redundant information that often is difficult to interpret. This study
      addresses the problem of selecting the most relevant gait features required to
      differentiate between assisted and non-assisted gait. For that purpose, it is
      presented an efficient approach that combines evolutionary techniques, based on
      genetic algorithms, and support vector machine algorithms, to discriminate
      differences between assisted and non-assisted gait with a walker with forearm
      supports. For comparison purposes, other classification algorithms are verified.
      Results with healthy subjects show that the main differences are characterized by
      balance and joints excursion in the sagittal plane. These results, confirmed by
      clinical evidence, allow concluding that this technique is an efficient feature
      selection approach. 

PMID- 24444752
TI  - Stereoscopic visualization of laparoscope image using depth information from 3D
      model.
AB  - Laparoscopic surgery is indispensable from the current surgical procedures. It
      uses an endoscope system of camera and light source, and surgical instruments
      which pass through the small incisions on the abdomen of the patients undergoing
      laparoscopic surgery. Conventional laparoscope (endoscope) systems produce 2D
      colored video images which do not provide surgeons an actual depth perception of
      the scene. In this work, the problem was formulated as synthesizing a stereo
      image of the monocular (conventional) laparoscope image by incorporating into
      them the depth information from a 3D CT model. Various algorithms of the computer
      vision including the algorithms for the feature detection, matching and tracking
      in the video frames, and for the reconstruction of 3D shape from shading in the
      2D laparoscope image were combined for making the system. The current method was
      applied to the laparoscope video at the rate of up to 5 frames per second to
      visualize its stereo video. A correlation was investigated between the depth maps
      calculated with our method with those from the shape from shading algorithm. The
      correlation coefficients between the depth maps were within the range of 0.70
      0.95 (P<0.05). A t-test was used for the statistical analysis. 

PMID- 24444753
TI  - Match-to-match variation in physical activity and technical skill measures in
      professional Australian Football.
AB  - OBJECTIVES: To determine the match-to-match variability in physical activity and
      technical performance measures in Australian Football, and examine the influence
      of playing position, time of season, and different seasons on these measures of
      variability. DESIGN: Longitudinal observational study. METHODS: Global
      positioning system, accelerometer and technical performance measures (total
      kicks, handballs, possessions and Champion Data rank) were collected from 33
      players competing in the Australian Football League over 31 matches during 2011
      2012 (N=511 observations). The global positioning system data were categorised
      into total distance, mean speed (mmin(-1)), high-speed running (>14.4 kmh(-1)),
      very high-speed running (>19.9 kmh(-1)), and sprint (>23.0 kmh(-1)) distance
      while player load was collected from the accelerometer. The data were log
      transformed to provide coefficient of variation and the between subject standard
      deviation (expressed as percentages). RESULTS: Match-to-match variability was
      increased for higher speed activities (high-speed running, very high-speed
      running, sprint distance, coefficient of variation %: 13.3-28.6%) compared to
      global measures (speed, total distance, player load, coefficient of variation %:
      5.3-9.2%). The between-match variability was relativity stable for all measures
      between and within AFL seasons, with only few differences between positions.
      Higher speed activities (high-speed running, very high-speed running, sprint
      distance), but excluding mean speed, total distance and player load, were all
      higher in the final third phase of the season compared to the start of the
      season. CONCLUSIONS: While global measures of physical performance are relatively
      stable, higher-speed activities and technical measures exhibit a large degree of
      between-match variability in Australian Football. However, these measures remain
      relatively stable between positions, and within and between Australian Football
      League seasons.

PMID- 24444754
TI  - Biomechanical variables and perception of comfort in running shoes with different
      cushioning technologies.
AB  - OBJECTIVES: To investigate the relationships between the perception of comfort
      and biomechanical parameters (plantar pressure and ground reaction force) during
      running with four different types of cushioning technology in running shoes.
      DESIGN: Randomized repeated measures. METHODS: Twenty-two men, recreational
      runners (18-45 years) ran 12km/h with running shoes with four different
      cushioning systems. Outcome measures included nine items related to perception of
      comfort and 12 biomechanical measures related to the ground reaction forces and
      plantar pressures. Repeated measure ANOVAs, Pearson correlation coefficients, and
      step-wise multiple regression analyses were employed (p<=0.05). RESULTS: No
      significant correlations were found between the perception of comfort and the
      biomechanical parameters for the four types of investigated shoes. Regression
      analysis revealed that 56% of the perceived general comfort can be explained by
      the variables push-off rate and pressure integral over the forefoot (p=0.015) and
      that 33% of the perception of comfort over the forefoot can be explained by
      second peak force and push-off rate (p=0.016). CONCLUSIONS: The results did not
      demonstrate significant relationships between the perception of comfort and the
      biomechanical parameters for the three types of shoes investigated (Gel, Air, and
      ethylene-vinyl acetate). Only the shoe with Adiprene+ technology had its general
      comfort and cushioning perception predicted by the loads over the forefoot. Thus,
      in general, one cannot predict the perception of comfort of a running shoe
      through impact and plantar pressure received.

PMID- 24444755
TI  - Protein microcapsules: preparation and applications.
AB  - Liposomes and polymerosomes generally represent the two most widely used carriers
      for encapsulating compounds, in particular drugs for delivery. While these are
      well established carriers, recent applications in biomedicine and food industry
      have necessitated the use of proteins as robust carriers that are stable under
      extreme acidic and basic conditions, have practically no toxicity and are able to
      withstand high shear force. This review highlights the different methods for
      using proteins as encapsulating materials and lists some biomedical applications
      of the microcapsules. The advantages and limitations in the capsules from the
      different preparation routes are enumerated. 

PMID- 24444756
TI  - Self-assemblies of luminescent rare earth compounds in capsules and multilayers.
AB  - This review addresses luminescent rare earth compounds assembled in microcapsules
      as well as in planar films fabricated by the layer-by-layer (LbL) technique, the
      Langmuir-Blodgett (LB) method and in self-assembled monolayers. Chemical
      precipitation, electrostatic, van der Waals interactions and covalent bonds are
      involved in the assembly of these compounds. Self-organized ring patterns of rare
      earth complexes in Langmuir monolayers and on planar surfaces with stripe
      patterns, as well as fluorescence enhancement due to donor-acceptor pairs,
      microcavities, enrichment of rare earth compounds, and shell protection against
      water are described. Recent information on the tuning of luminescence intensity
      and multicolors by the excitation wavelength and the ratio of rare earth ions,
      respectively, are also reviewed. Potential applications of luminescent rare earth
      complex assemblies serving as biological probes, temperature and gas sensors are
      pointed out. 

PMID- 24444757
TI  - Fractal dimension of time-resolved autofluorescence discriminates tumour from
      healthy tissues in the oral cavity.
AB  - Early detection and complete resection of oral carcinomas is of crucial
      importance for patient survival. This could be significantly improved by
      developing a non-invasive, sensitive and real-time detection technique. Time
      resolved autofluorescence measurement is state-of-the-art technology originally
      developed for non-destructive inspection of material. In this study, we measured
      time-resolved autofluorescence in tumours and healthy tissues of the oral cavity
      ex vivo and calculated the corresponding fractal dimension which was
      significantly higher in tumours than in healthy tissues (1.8 vs. 1.6, P < 0.001,
      unpaired t-test) with non-overlapping 95% confidential intervals 1.88-1.84 and
      1.57-1.69, respectively. Very high specificity (86%) could be reached at 100%
      sensitivity. The area under the curve was 99%, further suggesting the superior
      prediction potential of fractal dimension based on time-resolved autofluorescence
      spectra. 

PMID- 24444758
TI  - Interval between hysterectomy and start of radiation treatment is predictive of
      recurrence in patients with endometrial carcinoma.
AB  - PURPOSE: Adjuvant radiation therapy (RT) has been shown to improve local control
      in patients with endometrial carcinoma. We analyzed the impact of the time
      interval between hysterectomy and RT initiation in patients with endometrial
      carcinoma. METHODS AND MATERIALS: In this institutional review board-approved
      study, we identified 308 patients with endometrial carcinoma who received
      adjuvant RT after hysterectomy. All patients had undergone hysterectomy,
      oophorectomy, and pelvic and para-aortic lymph node evaluation from 1988 to 2010.
      Patients' demographics, pathologic features, and treatments were compared. The
      time interval between hysterectomy and the start of RT was calculated. The
      effects of time interval on recurrence-free (RFS), disease-specific (DSS), and
      overall survival (OS) were calculated. Following univariate analysis,
      multivariate modeling was performed. RESULTS: The median age and follow-up for
      the study cohort was 65 years and 72 months, respectively. Eighty-five percent of
      the patients had endometrioid carcinoma. RT was delivered with high-dose-rate
      brachytherapy alone (29%), pelvic RT alone (20%), or both (51%). Median time
      interval to start RT was 42 days (range, 21-130 days). A total of 269 patients
      (74%) started their RT <9 weeks after undergoing hysterectomy (group 1) and 26%
      started >= 9 weeks after surgery (group 2). There were a total of 43 recurrences.
      Tumor recurrence was significantly associated with treatment delay of >= 9 weeks,
      with 5-year RFS of 90% for group 1 compared to only 39% for group 2 (P<.001). On
      multivariate analysis, RT delay of >= 9 weeks (P<.001), presence of
      lymphovascular space involvement (P=.001), and higher International Federation of
      Gynecology and Obstetrics grade (P=.012) were independent predictors of
      recurrence. In addition, RT delay of >= 9 weeks was an independent significant
      predictor for worse DSS and OS (P=.001 and P=.01, respectively). CONCLUSIONS:
      Delay in administering adjuvant RT after hysterectomy was associated with worse
      survival endpoints. Our data suggest that shorter time interval between
      hysterectomy and start of RT may be beneficial.

PMID- 24444759
TI  - Four-dimensional magnetic resonance imaging using axial body area as respiratory
      surrogate: initial patient results.
AB  - PURPOSE: To evaluate the feasibility of a retrospective binning technique for 4
      dimensional magnetic resonance imaging (4D-MRI) using body area (BA) as a
      respiratory surrogate. METHODS AND MATERIALS: Seven patients with hepatocellular
      carcinoma (4 of 7) or liver metastases (3 of 7) were enrolled in an institutional
      review board-approved prospective study. All patients were simulated with both
      computed tomography (CT) and MRI to acquire 3-dimensional and 4D images for
      treatment planning. Multiple-slice multiple-phase cine-MR images were acquired in
      the axial plane for 4D-MRI reconstruction. Image acquisition time per slice was
      set to 10-15 seconds. Single-slice 2-dimensional cine-MR images were also
      acquired across the center of the tumor in orthogonal planes. Tumor motion
      trajectories from 4D-MRI, cine-MRI, and 4D-CT were analyzed in the superior
      inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions,
      respectively. Their correlation coefficients (CC) and differences in tumor motion
      amplitude were determined. Tumor-to-liver contrast-to-noise ratio (CNR) was
      measured and compared between 4D-CT, 4D-MRI, and conventional T2-weighted fast
      spin echo MRI. RESULTS: The means (+/- standard deviations) of CC comparing 4D
      MRI with cine-MRI were 0.97 +/- 0.03, 0.97 +/- 0.02, and 0.99 +/- 0.04 in SI, AP,
      and ML directions, respectively. The mean differences were 0.61 +/- 0.17 mm, 0.32
      +/- 0.17 mm, and 0.14 +/- 0.06 mm in SI, AP, and ML directions, respectively. The
      means of CC comparing 4D-MRI and 4D-CT were 0.95 +/- 0.02, 0.94 +/- 0.02, and
      0.96 +/- 0.02 in SI, AP, and ML directions, respectively. The mean differences
      were 0.74 +/- 0.02 mm, 0.33 +/- 0.13 mm, and 0.18 +/- 0.07 mm in SI, AP, and ML
      directions, respectively. The mean tumor-to-tissue CNRs were 2.94 +/- 1.51, 19.44
      +/- 14.63, and 39.47 +/- 20.81 in 4D-CT, 4D-MRI, and T2-weighted MRI,
      respectively. CONCLUSIONS: The preliminary evaluation of our 4D-MRI technique
      results in oncologic patients demonstrates its potential usefulness to accurately
      measure tumor respiratory motion with improved tumor CNR compared with 4D-CT.

PMID- 24444760
TI  - Accurate gene expression-based biodosimetry using a minimal set of human gene
      transcripts.
AB  - PURPOSE: Rapid and reliable methods for conducting biological dosimetry are a
      necessity in the event of a large-scale nuclear event. Conventional biodosimetry
      methods lack the speed, portability, ease of use, and low cost required for
      triaging numerous victims. Here we address this need by showing that polymerase
      chain reaction (PCR) on a small number of gene transcripts can provide accurate
      and rapid dosimetry. The low cost and relative ease of PCR compared with existing
      dosimetry methods suggest that this approach may be useful in mass-casualty
      triage situations. METHODS AND MATERIALS: Human peripheral blood from 60 adult
      donors was acutely exposed to cobalt-60 gamma rays at doses of 0 (control) to 10
      Gy. mRNA expression levels of 121 selected genes were obtained 0.5, 1, and 2 days
      after exposure by reverse-transcriptase real-time PCR. Optimal dosimetry at each
      time point was obtained by stepwise regression of dose received against
      individual gene transcript expression levels. RESULTS: Only 3 to 4 different gene
      transcripts, ASTN2, CDKN1A, GDF15, and ATM, are needed to explain >= 0.87 of the
      variance (R(2)). Receiver-operator characteristics, a measure of sensitivity and
      specificity, of 0.98 for these statistical models were achieved at each time
      point. CONCLUSIONS: The actual and predicted radiation doses agree very closely
      up to 6 Gy. Dosimetry at 8 and 10 Gy shows some effect of saturation, thereby
      slightly diminishing the ability to quantify higher exposures. Analyses of these
      gene transcripts may be advantageous for use in a field-portable device designed
      to assess exposures in mass casualty situations or in clinical radiation
      emergencies.

PMID- 24444761
TI  - Systems-level characterization of the kernel mechanism of the cyanobacterial
      circadian oscillator.
AB  - Circadian clock is an essential molecular regulatory mechanism that coordinates
      daily biological processes. Toward understanding the design principles of the
      circadian mechanism in cyanobacteria, the only prokaryotes reported to possess
      circadian rhythmicity, mathematical models have been used as important tools to
      help elucidate the complicated biochemical processes. In this study, we focus on
      elucidating the underlying systems properties that drive the oscillation of the
      cyanobacterial clockwork. We apply combined methods of time scale separation,
      phase space analysis, bifurcation analysis and sensitivity analysis to a model of
      the in vitro cyanobacterial circadian clock proposed by us recently. The original
      model is reduced to a three-dimensional slow subsystem by time scale separation.
      Phase space analysis of the reduced subsystem shows that the null-surface of the
      Serine-phosphorylated state (S-state) of KaiC is a bistable surface, and that the
      characteristic of the phase portrait indicates that the kernel mechanism of the
      clockwork behaves as a relaxation oscillator induced by interlinked positive and
      negative feedback loops. Phase space analysis together with perturbation analysis
      supports our previous viewpoint that the S-state of KaiC is plausibly a key
      component for the protein regulatory network of the cyanobacterial circadian
      clock. 

PMID- 24444762
TI  - Service providers' experiences and needs in working with refugees in the Geelong
      region: a qualitative study.
AB  - Service providers in Geelong, one of the priority locations for the resettlement
      of refugees in regional Australia, were interviewed to explore their perceptions
      of the health and wellbeing needs of refugees, and the capacity of service
      providers in a regional area to meet these. In all, 22 interviews were conducted
      with health and human service professionals in a range of organisations offering
      refugee-specific services, culturally and linguistically diverse (CALD) services
      in general, and services to the wider community, including refugees. The findings
      revealed that a more coordinated approach would increase the effectiveness of
      existing services; however, the various needs of refugees were more than could be
      met by organisations in the region at current resource levels. More staff and
      interpreting services were required, as well as professional development for
      staff who have had limited experience in working with refugees. It should not be
      assumed that service needs for refugees resettled in regional Australia will be
      the same as those of refugees resettled in capital cities. Some services provided
      in Melbourne were not available in Geelong, and there were services not currently
      provided to refugees that may be critical in facilitating resettlement in
      regional and rural Australia.

PMID- 24444763
TI  - Solid electrolytes for fluoride ion batteries: ionic conductivity in
      polycrystalline tysonite-type fluorides.
AB  - Batteries based on a fluoride shuttle (fluoride ion battery, FIB) can
      theoretically provide high energy densities and can thus be considered as an
      interesting alternative to Li-ion batteries. Large improvements are still needed
      regarding their actual performance, in particular for the ionic conductivity of
      the solid electrolyte. At the current state of the art, two types of fluoride
      families can be considered for electrolyte applications: alkaline-earth fluorides
      having a fluorite-type structure and rare-earth fluorides having a tysonite-type
      structure. As regard to the latter, high ionic conductivities have been reported
      for doped LaF3 single crystals. However, polycrystalline materials would be
      easier to implement in a FIB due to practical reasons in the cell manufacturing.
      Hence, we have analyzed in detail the ionic conductivity of La(1-y)Ba(y)F(3-y) (0
      <= y <= 0.15) solid solutions prepared by ball milling. The combination of DC and
      AC conductivity analyses provides a better understanding of the conduction
      mechanism in tysonite-type fluorides with a blocking effect of the grain
      boundaries. Heat treatment of the electrolyte material was performed and leads to
      an improvement of the ionic conductivity. This confirms the detrimental effect of
      grain boundaries and opens new route for the development of solid electrolytes
      for FIB with high ionic conductivities.

PMID- 24444764
TI  - Quantum chemical determination of molecular geometries, interpretation of FT-IR,
      FT-Raman spectra and charge transfer properties for N-(2-cyanoethyl)-N
      methylaniline.
AB  - FT-Raman and FT-IR spectra were recorded for N-(2-cyanoethyl)-N-methylaniline
      sample in solid state. The equilibrium geometries, harmonic vibrational
      frequencies, infrared and Raman scattering activities were computed using DFT
      method. Results obtained at this level of theory were used for a detailed
      interpretation of the infrared and Raman spectra, based on the potential energy
      distribution (PED) of the normal modes. Molecular parameters such as bond length,
      and bond angle were calculated with the same method. The intra-molecular charge
      transfer was calculated by means of natural bond orbital analysis (NBO).
      Hyperconjugative interaction energy was more during the pi-pi(*) transition.
      Energy gap of the molecule was found using HOMO and LUMO calculation, hence the
      less band gap, which seems to be more stable. Atomic charges of various atoms of
      title molecule and other thermo-dynamical parameters were calculated using same
      levels of calculation. The correlation equations between heat capacity, entropy,
      Gibb's free energies changes with temperatures were fitted by quadratic formula.
      UV-VIS spectral analyses of title molecule have been researched by theoretical
      calculations. In order to understand electronic transitions of the compound, TD
      DFT calculations on electronic absorption spectra in gas phase and solvent were
      performed. The calculated frontier orbital energies, absorption wavelengths
      (lambda), oscillator strengths (f) and excitation energies (E) for gas phase in
      different solvent are also illustrated. 

PMID- 24444766
TI  - How population heterogeneity in susceptibility and infectivity influences
      epidemic dynamics.
AB  - An important concern in public health is what population group should be
      prioritised for vaccination. To this end, we present an epidemic model with
      arbitrary initial distributions for population susceptibility, and corresponding
      infectivity distributions. We consider four scenarios: first, a population with
      heterogeneous susceptibility with a uniform distribution, but homogeneous
      infectivity; second, a heterogeneously susceptible population with linear
      heterogeneous infectivity functions, where the most susceptible are either the
      most or least infectious; third, a bimodal distribution for susceptibility, with
      all combinations of infectivity functions; finally, we consider the effects of
      additional pre-epidemic immunity, ostensibly through vaccination, on the epidemic
      dynamics. For a seasonal influenza-like infectious disease, we find the smallest
      final size and overall number of deaths due to the epidemic to occur if the most
      susceptible are vaccinated, corresponding to targeting children.

PMID- 24444765
TI  - A mathematical model of the sterol regulatory element binding protein 2
      cholesterol biosynthesis pathway.
AB  - Cholesterol is one of the key constituents for maintaining the cellular membrane
      and thus the integrity of the cell itself. In contrast high levels of cholesterol
      in the blood are known to be a major risk factor in the development of
      cardiovascular disease. We formulate a deterministic nonlinear ordinary
      differential equation model of the sterol regulatory element binding protein 2
      (SREBP-2) cholesterol genetic regulatory pathway in a hepatocyte. The
      mathematical model includes a description of genetic transcription by SREBP-2
      which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGCR), a main regulator of cholesterol
      synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2
      via a negative feedback formulation. Parameterised with data from the literature,
      the model is used to understand how SREBP-2 transcription and regulation affects
      cellular cholesterol concentration. Model stability analysis shows that the only
      positive steady-state of the system exhibits purely oscillatory, damped
      oscillatory or monotic behaviour under certain parameter conditions. In light of
      our findings we postulate how cholesterol homeostasis is maintained within the
      cell and the advantages of our model formulation are discussed with respect to
      other models of genetic regulation within the literature. 

PMID- 24444767
TI  - Beyond scoring: a modern histological assessment of chronic hepatitis should
      include tissue angiogenesis.

PMID- 24444768
TI  - Expanding our understanding of patient outcomes: the unique role of health
      services research in the continuing evolution of surgical science.

PMID- 24444769
TI  - Fear of falling in claudicants and its relationship to physical ability, balance,
      and quality of life.
AB  - OBJECTIVES: Intermittent claudication is associated with poor physical function,
      quality of life (QoL), and balance impairment. Fear of falling (FoF) is a
      recognized contributing factor to poor physical ability. Any link between
      claudication and FoF is yet to be determined. This study aimed to explore the
      prevalence of FoF in claudicants and its relationship with physical function and
      QoL. METHODS: A prospective observational study was performed. Fear of falling
      was determined using the Activities-specific Balance Confidence (ABC)
      questionnaire and the categorical question "Are you afraid of falling?" Physical
      ability and QoL (Short Form 36 and Vascular QoL) were determined. RESULTS: A
      total of 161 claudicants (118 men, median age of 69 years) were assessed; 83
      answered the categorical question "Are you afraid of falling?" By receiver
      operating characteristic curve analysis, an ABC threshold <74% denoted a FoF,
      which was associated with poorer physical function and QoL. CONCLUSION: Fear of
      falling is associated with poor physical, social, and psychological function,
      addressing this may improve all aspects of health.

PMID- 24444770
TI  - Alcohol and aging: the invisible epidemic.

PMID- 24444771
TI  - Psilocybin--summary of knowledge and new perspectives.
AB  - Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is
      nowadays given a lot of attention in the scientific community as a research tool
      for modeling psychosis as well as due to its potential therapeutic effects.
      However, it is also a very popular and frequently abused natural hallucinogen.
      This review summarizes all the past and recent knowledge on psilocybin. It
      briefly deals with its history, discusses the pharmacokinetics and
      pharmacodynamics, and compares its action in humans and animals. It attempts to
      describe the mechanism of psychedelic effects and objectify its action using
      modern imaging and psychometric methods. Finally, it describes its therapeutic
      and abuse potential. 

PMID- 24444772
TI  - Nursing unit teams matter: Impact of unit-level nurse practice environment, nurse
      work characteristics, and burnout on nurse reported job outcomes, and quality of
      care, and patient adverse events--a cross-sectional survey.
AB  - AIM: To investigate the impact of nurse practice environment factors, nurse work
      characteristics, and burnout on nurse reported job outcomes, quality of care, and
      patient adverse events variables at the nursing unit level. BACKGROUND: Nurse
      practice environment studies show growing insights and knowledge about
      determining factors for nurse workforce stability, quality of care, and patient
      safety. Until now, international studies have primarily focused on variability at
      the hospital level; however, insights at the nursing unit level can reveal key
      factors in the nurse practice environment. DESIGN: A cross-sectional design with
      a survey. METHOD: In a cross-sectional survey, a sample of 1108 nurses assigned
      to 96 nursing units completed a structured questionnaire composed of various
      validated instruments measuring nurse practice environment factors, nurse work
      characteristics, burnout, nurse reported job outcomes, quality of care, and
      patient adverse events. Associations between the variables were examined using
      multilevel modelling techniques. RESULTS: Various unit-level associations (simple
      models) were identified between nurse practice environment factors, nurse work
      characteristics, burnout dimensions, and nurse reported outcome variables.
      Multiple multilevel models showed various independent variables such as nursing
      management at the unit level, social capital, emotional exhaustion, and
      depersonalization as important predictors of nurse reported outcome variables
      such job satisfaction, turnover intentions, quality of care (at the unit, the
      last shift, and in the hospital within the last year), patient and family
      complaints, patient and family verbal abuse, patient falls, nosocomial
      infections, and medications errors. CONCLUSION: Results suggested a stable nurse
      work force, with the capability to achieve superior quality and patient safety
      outcomes, is associated with unit-level favourable perceptions of nurse work
      environment factors, workload, decision latitude, and social capital, as well low
      levels of burnout. Nurses, physicians, nursing leaders, and executives share
      responsibility to create an environment supportive of interdisciplinary team
      development.

PMID- 24444774
TI  - Polarization second harmonic generation by image correlation spectroscopy on
      collagen type I hydrogels.
AB  - Successful engineering of biomimetic tissue relies on an accurate quantification
      of the mechanical properties of the selected scaffold. To improve this
      quantification, typical bulk rheological measurements are often complemented with
      microscopic techniques, including label-free second harmonic generation (SHG)
      imaging. Image correlation spectroscopy (ICS) has been applied to obtain
      quantitative information from SHG images of fibrous scaffolds. However, the
      typical polarization SHG (P-SHG) effect, which partly defines the shape of the
      autocorrelation function (ACF), has never been taken into account. Here we
      propose a new and flexible model to reliably apply ICS to P-SHG images of fibrous
      structures. By starting from a limited number of straightforward assumptions and
      by taking into account the P-SHG effect, we were able to cope with the typically
      observed ACF particularities. Using simulated datasets, the resulting model was
      thoroughly evaluated and compared with models previously described in the
      literature. We showed that our new model has no restrictions concerning the fibre
      length for the density retrieval. For certain length ranges, the model can
      additionally be used to obtain the average fibre length and the P-SHG related non
      zero susceptibility tensor element ratios. From experimental data on collagen
      type I hydrogels, values of SHG tensor element ratios and fibre thickness were
      determined which match values reported in the literature, thereby underpinning
      the validity and applicability of our new model. 

PMID- 24444773
TI  - The multiple, complex roles of versican and its proteolytic turnover by ADAMTS
      proteases during embryogenesis.
AB  - Embryonic development is an exceptionally dynamic process, requiring a
      provisional extracellular matrix that is amenable to rapid remodeling, and
      proteolytic or non-proteolytic mechanisms that can remodel the major components
      of this matrix. Versican is a chondroitin-sulfate proteoglycan that forms highly
      hydrated complexes with hyaluronan and is widely distributed in the provisional
      matrix of mammalian embryos. It has been extensively studied in the context of
      cardiovascular morphogenesis, neural crest cell migration and skeletal
      development. Analysis of Vcan transgenic mice has established the requirement for
      versican in cardiac development and its role in skeletogenesis. The ADAMTS family
      includes several versican-degrading proteases that are active during remodeling
      of the embryonic provisional matrix, especially during sculpting of versican-rich
      tissues. Versican is cleaved at specific peptide bonds by ADAMTS proteases, and
      the cleavage products are detectable by neo-epitope antibodies. Myocardial
      compaction, closure of the secondary palate (in which neural crest derived cells
      participate), endocardial cushion remodeling, myogenesis and interdigital web
      regression are developmental contexts in which ADAMTS-mediated versican
      proteolysis has been identified as a crucial requirement. ADAMTS proteases are
      expressed coordinately and function cooperatively in many of these contexts. In
      addition to versican clearance, ADAMTS proteases generate a bioactive versican
      fragment containing the N-terminal G1 domain, which we have named versikine. This
      review promotes the view that the embryonic extracellular matrix has evolved not
      only to provide a permissive environment for embryo growth and morphogenesis, but
      through its dissolution to influence and regulate cellular processes. 

PMID- 24444775
TI  - Red and blue lights induced oxidative stress tolerance promote cadmium
      rhizocomplexation in Oryza sativa.
AB  - Cadmium (Cd) accumulation and related stress responses have been investigated in
      red, blue and white lights exposed Oryza sativa L. cv MTU 7029. Cd translocation
      was reduced significantly by red and blue lights. Increase in amount of organic
      acids, thiols, and nutrients in the roots that cause Cd rhizocomplexation was the
      reason for reduction in Cd translocation. These effects were due to higher
      efficiency to perform photosynthesis and transpiration under red or blue lights
      compare with white light during Cd stress. Increased photosynthetic assimilate
      turnover was witnessed as a function of sugar content. Amount of redox regulators
      such as glutathione and ascorbate were also increased under red and blue light
      exposure. Together with up regulation of antioxidant enzyme activities, these
      metabolites ensured redox balance in presence of reactive oxygen species produced
      due to Cd toxicity. Protection of photosynthesis from Cd inducible oxidative
      stress ensured supplies of sugar intermediates essential for the synthesis of
      metal chelators in roots. Therefore, it was inferred that red and blue lights
      promote Cd rhizocomplexation and ameliorated Cd stress in rice seedlings. 

PMID- 24444776
TI  - Positive therapy of andrographolide in vocal fold leukoplakia.
AB  - PURPOSE: Vocal fold leukoplakia is a premalignant precursor of squamous cell
      carcinoma. Although many efforts have been contributed to therapy of this
      disease, none exhibits a satisfactory result. The aims of this study were to
      investigate the effectiveness and feasibility of andrographolide therapy in vocal
      fold leukoplakia and to explore the preliminary mechanism underlying. MATERIALS
      AND METHODS: Forty-one eligible patients were enrolled in the study. The patients
      were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection
      aerosols twice a day, and 2 weeks was considered as one treatment course.
      Electronic laryngoscope was used to observe the condition of vocal fold
      leukoplakia during the treatment. Every patient received one or two treatment
      courses, and the follow-up was carried out for 12 months. Toxic reactions of
      treatments were evaluated on the basis of the standards of the United States MD
      Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied
      to explore the mechanism of effect of andrographolide. Anti-proliferative effect
      on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases
      (MAPK) and pro-apoptotic protein were detected after andrographolide treatment.
      RESULTS: We found that andrographolide exhibited significant curative effects on
      treatments, which were accompanied by thinning of the lesion of leukoplakia,
      reduction in the whitish surface area, and return of pink or red epithelium. A
      complete response up to 85% was observed, and no toxic side effect events
      occurred during the study. No patient with a complete response had a recurrence
      in the follow-up. Moreover, cellular experiments in Hep2 indicated that
      andrographolide activated MAPK pathway and caspase cascade, and finally induced
      apoptosis in laryngeal carcinoma cell. CONCLUSIONS: The advantages of
      andrographolide are connected with minimally invasive and localized character of
      the treatment and no damage of collagenous tissue structures, which are more
      convenient and less painful for patients. These results suggest that
      andrographolide treatment is a viable strategy for curing vocal fold leukoplakia.

PMID- 24444777
TI  - Margins of stability in young adults with traumatic transtibial amputation
      walking in destabilizing environments.
AB  - Understanding how lower-limb amputation affects walking stability, specifically
      in destabilizing environments, is essential for developing effective
      interventions to prevent falls. This study quantified mediolateral margins of
      stability (MOS) and MOS sub-components in young individuals with traumatic
      unilateral transtibial amputation (TTA) and young able-bodied individuals (AB).
      Thirteen AB and nine TTA completed five 3-min walking trials in a Computer
      Assisted Rehabilitation ENvironment (CAREN) system under each of three test
      conditions: no perturbations, pseudo-random mediolateral translations of the
      platform, and pseudo-random mediolateral translations of the visual field.
      Compared to the unperturbed trials, TTA exhibited increased mean MOS and MOS
      variability during platform and visual field perturbations (p<0.010). AB
      exhibited increased mean MOS during visual field perturbations and increased MOS
      variability during both platform and visual field perturbations (p<0.050). During
      platform perturbations, TTA exhibited significantly greater values than AB for
      mean MOS (p<0.050) and MOS variability (p<0.050); variability of the lateral
      distance between the center of mass (COM) and base of support at initial contact
      (p<0.005); mean and variability of the range of COM motion (p<0.010); and
      variability of COM peak velocity (p<0.050). As determined by mean MOS and MOS
      variability, young and otherwise healthy individuals with transtibial amputation
      achieved lateral stability similar to that of their able-bodied counterparts
      during unperturbed and visually-perturbed walking. However, based on mean and
      variability of MOS, unilateral transtibial amputation was shown to have affected
      lateral walking stability during platform perturbations. 

PMID- 24444778
TI  - Adoptive transfer of hepatic stellate cells ameliorates liver ischemia
      reperfusion injury through enriching regulatory T cells.
AB  - Our previous study indicated that adoptive transferred regulatory T cells (Tregs)
      attenuated liver ischemia reperfusion injury (IRI). Recent studies demonstrated
      that hepatic stellate cells (HSCs) were producers of induced Tregs (iTregs) via
      retinoic acid. This study aimed to investigate the role of adoptive transferred
      HSCs in liver IRI. Mice were treated with gradient doses of HSCs before surgery
      at 24h or 72h. The levels of serum aminotransferases and hepatic cytokines were
      evaluated after reperfusion. Meanwhile, hepatic Tregs and their subsets were
      analyzed by flow cytometry. We found that adoptive transferred HSCs attenuated
      liver IRI. Administration of HSCs expanded the number of hepatic iTregs and
      natural Tregs (nTregs) after reperfusion. In addition, we found that the
      increased Tregs were almost Helios-Tregs before surgery. These Helios-Tregs were
      considered as iTregs and protected liver from IRI partially. Furthermore,
      adoptive transferred HSCs stabilized nTregs and prevented nTregs from reducing
      after reperfusion. These nTregs also attenuated liver IRI partially. Depletion of
      Tregs abolished the protective effect of HSCs. Thus, we conclude that adoptive
      transferred HSCs ameliorate liver IRI in Tregs-dependent manner. 

PMID- 24444779
TI  - Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide
      treatment.
AB  - Rheumatoid arthritis (RA) is a disease that is still insufficiently controlled by
      current treatments. Poly(ADP-ribose) polymerase (PARP) inhibitors ameliorate
      immune-mediated diseases in several experimental models, including RA, colitis,
      experimental autoimmune encephalomyelitis and allergy. Together these findings
      showed that ADP-ribosylating enzymes, in particular PARP-1, play a pivotal role
      in the regulation of immune responses and may represent a noble target for new
      therapeutic approaches in immune-mediated diseases. The effect of 3
      aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) synthetase activity, was
      evaluated in a mouse model of adjuvant-induced arthritis (AIA) on pro
      inflammatory cytokines, adhesion molecules, inflammatory mediators and chemokine
      production/expression in serum and knee joint. Histopathological examination was
      also done on joint section. Our data demonstrates that 3-AB, 10mg/kg,
      intraperitoneally (i.p.) significantly reduces pro-inflammatory cytokine (IL-17,
      TNF-alpha and IL-2) and chemokine (MCP-1 and MIP-2) production/expression,
      accompanied by amelioration of the disease as indicated by reduced paw swelling
      and arthritic scores and was associated with a significant reduction of VCAM-1
      and ICAM-1 expression in the knee joint. Moreover, the expression of inflammatory
      mediators (iNOS, COX-2, MMP-2, MMP-9) and joint histological inflammatory damage
      was also markedly decreased. The results of this study suggest that PARP-1
      inhibitor may play a role in the inflammatory arthritic process after
      administration of 3-AB may be a beneficial therapeutic approach. 

PMID- 24444780
TI  - Usefulness of preoperative cardiac dimensions to predict success of reverse
      cardiac remodeling in patients undergoing repair for mitral valve prolapse.
AB  - Mitral valve repair for mitral regurgitation (MR) is currently recommended based
      on the degree of MR and left ventricular (LV) function. The present study
      examines predictors of reverse remodeling after repair for degenerative disease.
      We retrospectively identified 439 patients who underwent repair for myxomatous
      mitral valve degeneration and had both pre- and postoperative echocardiographic
      data available. Patients were categorized based on left atrial (LA) diameter and
      LV diameter standards of the American Society of Echocardiography. The outcome of
      interest was the degree of reverse remodeling on all heart dimensions at follow
      up. Mean age was 57 +/- 12 years, and 37% of patients were women. Mean
      preoperative LV end-diastolic diameter was 5.8 +/- 0.7 cm, LV end-systolic
      diameter 3.5 +/- 0.6 cm, LA 4.7 +/- 0.7 cm, and median ejection fraction 60%.
      Median observation time was 81 months, and time to postoperative echocardiography
      was 38 months. Overall, 95% of patients had normal LV diastolic dimensions
      postoperatively, 93% normal LV systolic dimensions, and 37% normal LA dimensions.
      A Cox regression analysis showed that moderate (odds ratio [OR] 2.1, 95%
      confidence interval [CI] 1.3 to 3.4) or severe preoperative LA dilatation (OR
      2.7, 95% CI 1.7 to 4.4), abnormal preoperative LV end-systolic dimensions (OR
      1.3, 95% CI 1.1 to 1.5), and age in years (OR 1.02, 95% CI 1.01 to 1.03) were
      predictive of less reverse remodeling on follow-up. In conclusion, preoperative
      LV end-systolic dimensions and LA dilatation substantially affect the likelihood
      of successful LA remodeling and normalization of all heart dimensions after
      mitral valve repair for MR. These findings support early operation for MR before
      the increase in heart dimensions is nonreversible.

PMID- 24444781
TI  - Association of aspirin dose and vorapaxar safety and efficacy in patients with
      non-ST-segment elevation acute coronary syndrome (from the TRACER Trial).
AB  - Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary
      Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk
      patients with non-ST-segment elevation acute coronary syndrome. We explored
      aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates
      were compared in groups defined by ASA dose (low, medium, and high). Landmark
      analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181
      to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were
      treated with low-, medium-, and high-dose ASA at baseline, respectively.
      Participants enrolled in North America versus elsewhere were more often treated
      with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted
      cardiovascular death, myocardial infarction, stroke, hospitalization for
      ischemia, or urgent revascularization event rates tended to be higher with higher
      baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend = 0.15573).
      Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of
      vorapaxar on cardiovascular (unadjusted p for interaction = 0.065; adjusted p for
      interaction = 0.140) and bleeding (unadjusted p for interaction = 0.915; adjusted
      p for interaction = 0.954) outcomes were similar across groups. Landmark analyses
      showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA
      dose at each time point except for 0 to 30 days, when vorapaxar tended to be
      worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p
      for interaction = 0.0157). In conclusion, most TRACER participants were treated
      with low-dose ASA, although a high dose was common in North America. High-dose
      participants tended to have higher rates of ischemic and bleeding outcomes.
      Although formal statistical testing did not reveal heterogeneity in vorapaxar's
      effect across dose subgroups, consistent trends support use of low-dose ASA with
      other antiplatelet therapies.

PMID- 24444782
TI  - Prediction of coronary artery disease severity using CHADS2 and CHA2DS2-VASc
      scores and a newly defined CHA2DS2-VASc-HS score.
AB  - As the CHADS2 and CHA2DS2-VASc scores include similar risk factors for the
      development of coronary artery disease (CAD), they may provide crucial
      information regarding the severity of coronary artery lesions and the risk of
      thromboembolism. To increase the likelihood of determining CAD severity, we
      formulated the CHA2DS2-VASc-HS score comprising hyperlipidemia and smoking in
      addition to the components of the CHA2DS2-VASc score and male instead of female
      gender. We aimed to investigate whether these 3 risk scores can be used to
      predict CAD severity. A total of 407 consecutive patients who underwent coronary
      angiography were enrolled in the study. Presence of >50% stenosis in a coronary
      artery was assessed as significant CAD. Of the patients, 87 had normal coronary
      angiograms and served as group 1. The remaining 320 patients with coronary
      stenosis were further classified into 2 groups according to CAD with stenosis of
      <50% or >=50%: 123 patients with mild CAD as group 2 and 197 patients with severe
      CAD as group 3. The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-HS scores were
      significantly different among the 3 groups. The CHADS2, CHA2DS2-VASc, and CHA2DS2
      VASc-HS scores correlated significantly with the number of diseased vessels (r =
      0.406, p <0.001; r = 0.308, p <0.001; and r = 0.533, p <0.001, respectively) and
      the Gensini score (r = 0.383, p <0.001; r = 0.300, p <0.001; and r = 0.500, p
      <0.001, respectively). The CHA2DS2-VASc-HS score was found to be the best scoring
      scheme to predict CAD severity in the area under the curve comparison of these
      scoring systems. For prediction of severe CAD, the cut-off value of CHA2DS2-VASc
      HS score was >2 with a sensitivity of 85.2% and a specificity of 57.5% (area
      under the curve 0.802, 95% confidence interval 0.760 to 0.839, p <0.001). In
      conclusion, our findings suggest that the CHADS2, CHA2DS2-VASc, and especially
      CHA2DS2-VASc-HS scores could be considered predictive of the risk of severe CAD.

PMID- 24444783
TI  - Interaction between leukocytes and erythrocytes in the human retina: effects of
      pentoxifylline on hyperoxia-induced vasoconstriction during increased neutrophil
      counts.
AB  - PURPOSE: Pentoxifylline, a nonselective phosphodiesterase inhibitor, shows
      vasodilator effects in certain vascular beds and reduces blood viscosity. We have
      previously shown that under states of vasoconstriction an interaction between
      circulating erythrocytes and leukocytes may play a role in the control of blood
      flow. The reason for this observation is not entirely clear but may be related to
      a mechanical interaction between red and white blood cells. In the present study
      we hypothesized that pentoxifylline may alter this interaction during oxygen
      induced vasoconstriction. METHODS: 24 healthy male subjects participated in this
      double masked, randomized, placebo-controlled 2 way cross over trial. In order to
      increase white blood cell count (WBC) count, 300 MUg of G-CSF was administered
      intravenously. Vasoconstriction of retinal vessels was induced by oxygen
      inhalation. 400mg of pentoxifylline or placebo was infused at two different study
      days. White blood cell flux was assessed with the blue-field entoptic technique.
      Vessel calibers were measured with a dynamic vessel analyzer (DVA) and red blood
      cell velocity (RBCV) was determined with laser Doppler velocimetry (LDV). Retinal
      blood flow was calculated based on retinal vessel diameters and RBCV. RESULTS:
      Administration of G-CSF induced a significant increase in WBC, both in the
      placebo and the pentoxifylline group (p<0.01 for both groups). Retinal vessel
      diameter, RBCV, calculated retinal blood flow and white blood cell flow were not
      altered by administration of pentoxifylline. Hyperoxia induced a pronounced
      decrease in retinal blood flow parameters. No difference was observed between
      groups during oxygen breathing in vessel diameters (p=0.54), RBCV (p=0.34),
      calculated retinal blood flow (p=0.3) and white blood cell flow (p=0.26).
      CONCLUSION: Our data indicate that short time administration of pentoxifylline
      does not alter the oxygen-induced effect on ocular blood flow parameters during
      leukocytosis. Whether long-term treatment could improve retinal blood flow under
      states of vasoconstriction remains to be investigated.

PMID- 24444784
TI  - Functional slit lamp biomicroscopy for imaging bulbar conjunctival
      microvasculature in contact lens wearers.
AB  - PURPOSE: To develop, test and validate functional slit lamp biomicroscopy (FSLB)
      for generating non-invasive bulbar conjunctival microvascular perfusion maps
      (nMPMs) and assessing morphometry and hemodynamics. METHODS: FSLB was adapted
      from a traditional slit-lamp microscope by attaching a digital camera to image
      the bulbar conjunctiva to create nMPMs and measure venular blood flow
      hemodynamics. High definition images with a large field of view were obtained on
      the temporal bulbar conjunctiva for creating nMPMs. A high imaging rate of 60
      frames per second and an ~210* high magnification were achieved using the camera
      inherited high speed setting and Movie Crop Function, for imaging hemodynamics.
      Custom software was developed to segment bulbar conjunctival nMPMs for further
      fractal analysis and quantitatively measure blood vessel diameter, blood flow
      velocity and flow rate. Six human subjects were imaged before and after 6h of
      wearing contact lenses. Monofractal and multifractal analyses were performed to
      quantify fractality of the nMPMs. RESULTS: The mean bulbar conjunctival vessel
      diameter was 18.8 +/- 2.7 MUm at baseline and increased to 19.6 +/- 2.4 MUm after
      6h of lens wear (P=0.020). The blood flow velocity was increased from 0.60 +/-
      0.12 mm/s to 0.88 +/- 0.21 mm/s (P=0.001). The blood flow rate was also increased
      from 129.8 +/- 59.9 pl/s to 207.2 +/- 81.3 pl/s (P=0.001). Bulbar conjunctival
      nMPMs showed the intricate details of the bulbar conjunctival microvascular
      network. At baseline, fractal dimension was 1.63 +/- 0.05 and 1.71 +/- 0.03
      analyzed by monofractal and multifractal analyses, respectively. Significant
      increases in fractal dimensions were found after 6h of lens wear (P<0.05).
      CONCLUSIONS: Microvascular network's fractality, morphometry and hemodynamics of
      the human bulbar conjunctiva can be measured easily and reliably using FSLB. The
      alternations of the fractal dimensions, morphometry and hemodynamics during
      contact lens wear may indicate ocular microvascular responses to contact lens
      wear.

PMID- 24444785
TI  - Comparative analysis of binary and ternary cyclodextrin complexes with econazole
      nitrate in solution and in solid state.
AB  - The aim of this work was to investigate in-depth interactions of econazole
      nitrate (ECN), a very poorly water-soluble antifungal agent, with different beta
      cyclodextrin (betaCD) derivatives, and to evaluate the potential synergistic
      effect of suitable third compounds (l-amino acids, citric acid, hydrophilic
      polymers). Phase-solubility studies showed the formation of equimolar complexes
      with all tested CDs, and indicated sulfobutyl-betaCD (SBEbetaCD) as the best
      complexing and solubilizing agent for ECN, followed by hydroxypropyl-betaCD
      (HPbetaCD). 1D and 2D (1)H NMR studies demonstrated the actual formation of
      inclusion complexes of 1:1mol:mol stoichiometry, and gave insight about different
      inclusion modes of ECN molecule into the CD cavity, simultaneously existing in
      solution. Among the different tested ternary systems, only those with citric acid
      (CA) enabled a significant increase in complexing and solubilizing ability
      towards the drug with respect to the binary ones, indicating a synergistic effect
      between SBEbetaCD and CA and the formation of highly soluble ternary complexes,
      which was further supported by NMR studies. Solid equimolar binary and ternary
      systems of ECN, CDs and CA were prepared by co-grinding in high energy
      vibrational micro-mills and characterized by differential scanning calorimetry, X
      ray powder diffractometry and in vitro dissolution studies. In the case of binary
      systems, total sample amorphization, indicative of strong solid state
      interactions and possible inclusion complex formation, was obtained only for co
      ground products with HPbetaCD and SBEbetaCD, but they both presented a
      dissolution profile typical of a supersaturated system, with a limited
      improvement of drug dissolution efficiency (8.3 and 22.13 times, respectively).
      On the contrary, the ternary ECN/SBEbetaCD/CA co-ground product presented
      superior dissolution properties, increasing the ECN dissolution efficiency of
      66.62 times, clearly having the best potential for further development of a novel
      ECN delivery system for efficient delivery of the drug to the oral cavity, thus
      improving the therapy of oral candidosis. 

PMID- 24444786
TI  - Role of astrocytes in the neuroprotective actions of 17beta-estradiol and
      selective estrogen receptor modulators.
AB  - Neuroprotective actions of 17beta-estradiol (estradiol) are in part mediated by
      direct actions on neurons. Astrocytes, which play an essential role in the
      maintenance of the homeostasis of neural tissue, express estrogen receptors and
      are also involved in the neuroprotective actions of estradiol in the brain.
      Estradiol controls gliosis and regulates neuroinflammation, edema and glutamate
      transport acting on astrocytes. In addition, the hormone regulates the release of
      neurotrophic factors and other neuroprotective molecules by astrocytes. In
      addition, reactive astrocytes are a local source of neuroprotective estradiol for
      the injured brain. Since estradiol therapy is not free from peripheral risks,
      alternatives for the hormone have been explored. Some selective estrogen receptor
      modulators (SERMs), which are already in use in clinical practice for the
      treatment of breast cancer, osteoporosis or menopausal symptoms, exert similar
      actions to estradiol on astrocytes. Therefore, SERMs represent therapeutic
      alternatives to estradiol for the activation of astroglia-mediated
      neuroprotective mechanisms. 

PMID- 24444788
TI  - Synthesis and characterization of wollastonite glass-ceramics for dental implant
      applications.
AB  - OBJECTIVES: To synthesize a glass-ceramic (GC) that is suitable for non-metallic
      one-piece dental implant application. METHODS: Three glasses in a SiO2-Al2O3-CaO
      CaF2-K2O-B2O3-P2O5-CeO2-Y2O3 system were produced by wet chemistry. Differential
      thermal analysis (DTA) was carried out to determine the glass crystallization
      kinetic parameters and the heating schedules that were used for sintering of GCs.
      Crystalline phases and crystal morphologies were studied by X-ray diffraction
      (XRD) and scanning electron microscopy (SEM), respectively. Mechanical properties
      of the GCs were determined by ultrasonic and indentation tests and its
      machinability were evaluated. Chemical durability was carried out according to
      ISO 6872, whereas testing chemical degradation in tris buffered solution was
      executed according to ISO 10993-14. RESULTS: XRD of the GC specimens showed that
      wollastonite was the main crystalline with other secondary phases; GC2 had
      cristobalite as an additional phase. SEM of the GCs revealed dense acicular
      interlocking crystals. Young's modulus of elasticity (E), true hardness (Ho) and
      fracture toughness (KIC) of the GCs were 89-100GPa, 4.85-5.17GPa and 4.62
      5.58MPam(0.5), respectively. All GCs were demonstrated excellent machinability.
      The GCs exhibited various chemical durability and degradation rates. KIC values
      of the GCs following chemical durability testing were not significantly different
      from those of the original materials (p>0.05). GC2 exhibited significantly higher
      KIC value compared with GC1 and GC3 (p<0.05) and its chemical durability
      satisfied ISO 6872 specification for dental ceramics. SIGNIFICANCE: Wollastonite
      cristobalite GC can be considered as a promising material for one-piece dental
      implant applications due to its strength, machinability and chemical durability.

PMID- 24444789
TI  - Remineralization potential of fully demineralized dentin infiltrated with silica
      and hydroxyapatite nanoparticles.
AB  - OBJECTIVE: This study investigates the potential of a novel guided tissue
      regeneration strategy, using fully demineralized dentin infiltrated with silica
      and hydroxyapatite (HA) nanoparticles (NPs), to remineralize dentin collagen that
      is completely devoid of native hydroxyapatite. METHODS: Dentin blocks were fully
      demineralized with 4N formic acid and subsequently infiltrated with silica and HA
      NPs. The remineralizing potential of infiltrated dentin was assessed following a
      twelve week exposure to an artificial saliva solution by means of TEM, EDS and
      micro-CT. Measurements were taken at baseline and repeated at regular intervals
      for the duration of the study to quantify the P and Ca levels, the mineral volume
      percentage and mineral separation of the infiltrated dentin specimens compared to
      sound dentin and non-infiltrated controls. RESULTS: Infiltration of demineralized
      dentin with nano-HA restored up to 55% of the P and Ca levels at baseline. A
      local increase in the concentration of calcium phosphate compounds over a period
      of twelve weeks resulted in a higher concentration in P and Ca levels within the
      infiltrated specimens when compared to the non-infiltrated controls.
      Remineralization of demineralized dentin with silica NPs by immersion in
      artificial saliva was the most effective strategy, restoring 20% of the P levels
      of sound dentin. Micro-CT data showed a 16% recovery of the mineral volume in
      dentin infiltrated with silica NPs and a significant decrease in the mineral
      separation to levels comparable to sound dentin. SIGNIFICANCE: Demineralized
      dentin infiltrated with silica NPs appears to encourage heterogeneous
      mineralization of the dentin collagen matrix following exposure to an artificial
      saliva solution.

PMID- 24444790
TI  - Supporting pre-registration nursing students in their exploration of death and
      dying.
AB  - Student nurses will be exposed to dying patients from the very start of their
      education. The authors believe that nurse lecturers have a duty of care towards
      both the student and the patient in preparing them to cope with this experience.
      End of life care deserves further emphasis within the forum of nurse education.
      Within this article the authors outline their introduction of a new teaching
      session at the beginning of the pre-registration nursing curriculum at Birmingham
      City University to help prepare student nurses from all four fields of nursing to
      participate in end of life care. This flexible session entitled 'perceptions of
      dying' allows the students to explore their fears, anxieties and expectations of
      caring for a patient at the end of their life and discusses the mechanisms
      available for seeking support. The purpose of this article is to raise debate
      about the teaching of the subject of death and dying within pre-registration
      nurse education and to show case the lesson concept that the authors believe
      could be disseminated further to address this student need. 

PMID- 24444791
TI  - Rapid microwave-assisted green synthesis of 3D hierarchical flower-shaped NiCo2O4
      microsphere for high-performance supercapacitor.
AB  - Binary metal oxides with three-dimensional (3D) superstructure have been regarded
      as desirable electrode materials for the supercapacitor due to the combination of
      the improved electrical conductivity and effective porous structure. 3D
      hierarchical flower-shaped nickel cobaltite (NiCo2O4) microspheres have been
      fabricated by a rapid and template-free microwave-assisted heating (MAH) reflux
      approach followed by pyrolysis of the as-prepared precursors. The flower-shaped
      NiCo2O4 microspheres, composed of ultrathin nanopetals with thickness of about 15
      nm, are endowed with large specific surface area (148.5 m(2) g(-1)) and a narrow
      pore size distribution (5-10 nm). The as-fabricated porous flower-shaped NiCo2O4
      microspheres as electrode materials for supercapacitor exhibited high specific
      capacitance of 1006 F g(-1) at 1 A g(-1), enhanced rate capability, and excellent
      electrochemical stability with 93.2% retention after 1000 continuous charge
      discharge (CD) cycles even at a high current density of 8 A g(-1). The desirable
      integrated performance enables it to be a promising electrode material for the
      electrochemical supercapacitor (EC). 

PMID- 24444793
TI  - Intracranial aneurysm formation following radiation.

PMID- 24444794
TI  - Effects of ionizing radiation on cerebral vasculature.

PMID- 24444792
TI  - Selective regulation of axonal growth from developing hippocampal neurons by
      tumor necrosis factor superfamily member APRIL.
AB  - APRIL (A Proliferation-Inducing Ligand, TNFSF13) is a member of the tumor
      necrosis factor superfamily that regulates lymphocyte survival and activation and
      has been implicated in tumorigenesis and autoimmune diseases. Here we report the
      expression and first known activity of APRIL in the nervous system. APRIL and one
      of its receptors, BCMA (B-Cell Maturation Antigen, TNFRSF17), are expressed by
      hippocampal pyramidal cells of fetal and postnatal mice. In culture, these
      neurons secreted APRIL, and function-blocking antibodies to either APRIL or BCMA
      reduced axonal elongation. Recombinant APRIL enhanced axonal elongation, but did
      not influence dendrite elongation. The effect of APRIL on axon elongation was
      inhibited by anti-BCMA and the expression of a signaling-defective BCMA mutant in
      these neurons, suggesting that the axon growth-promoting effect of APRIL is
      mediated by BCMA. APRIL promoted phosphorylation and activation of ERK1, ERK2 and
      Akt and serine phosphorylation and inactivation of GSK-3beta in cultured
      hippocampal pyramidal cells. Inhibition of MEK1/MEK2 (activators of ERK1/ERK2),
      PI3-kinase (activator of Akt) or Akt inhibited the axon growth-promoting action
      of APRIL, as did pharmacological activation of GSK-3beta and the expression of a
      constitutively active form of GSK-3beta. These findings suggest that APRIL
      promotes axon elongation by a mechanism that depends both on ERK signaling and
      PI3-kinase/Akt/GSK-3beta signaling. 

PMID- 24444795
TI  - Surgical excision margins for melanoma in situ.
AB  - INTRODUCTION: Melanoma in situ (MIS) is a non-invasive lesion accounting for up
      to 27% of all melanomas by Coory et al. (2006).(1) MIS may be a precursor to
      invasive disease. The Lentigo Maligna (LM) subgroup of MIS carries upto a 4.7%
      lifetime risk of developing an invasive component by Agarwal-Antal et al.
      (2002).(2) Surgical excision is recommended however other modalities of
      treatments are possible. In this study we aim to assess whether histological
      margins following excision of in situ melanoma has any bearing on recurrence or
      progression to malignancy. METHOD: We retrospectively reviewed data accumulated
      on all melanomas referred to the hospital between the dates of February 2001 to
      February 2009. We identified all patients with melanoma in situ and for these
      patients recorded age, sex, anatomical site of lesion, histological type,
      histological excision margin, recurrence after excision and transformation to
      malignant melanoma. RESULTS: A total of 2121 patents were identified having been
      diagnosed and treated for melanoma of which 192 cases were identified with
      melanoma in situ representing 9.1% of all melanomas treated. 38% of all the
      lesions were of the LM subgroup. We noted a higher incomplete excision rate in
      this subgroup (p < 0.01) compared to the non-LM subgroup. We only noted two
      recurrences following complete excision (1.1%) and one recurrence in lesions
      completely excised with histological margins less than 2 mm (1.4%). Both of the
      lesions that recurred following complete excision were LM lesions. Recurrence
      following complete excision of LM was 2.9%. CONCLUSION: Our data suggests that
      MIS lesions that were not LM and adequately excised even with narrow margins are
      unlikely to recur therefore reducing the need for wider excision. LM however
      poses a more challenging clinical problem not only with the higher inadequate
      primary excision and higher recurrence rates following excision but also the fact
      that it occurs in much older patients who may be less able to tolerate more
      extensive surgery. In keeping with the literature we would suggest treating LM
      lesions more aggressively if possible.

PMID- 24444796
TI  - Recurrence of invasive ductal breast carcinoma 10 months after autologous fat
      grafting.

PMID- 24444797
TI  - Using nasopharyngeal tube to stent external auditory canal in atresia repair.

PMID- 24444798
TI  - Undergraduate exposure to plastic surgery: the medical student perspective.

PMID- 24444799
TI  - Subunit interactions in pig-kidney fructose-1,6-bisphosphatase: binding of
      substrate induces a second class of site with lowered affinity and catalytic
      activity.
AB  - BACKGROUND: Fructose-1,6-bisphosphatase, a major enzyme of gluconeogenesis, is
      inhibited by AMP, Fru-2,6-P2 and by high concentrations of its substrate Fru-1,6
      P2. The mechanism that produces substrate inhibition continues to be obscure.
      METHODS: Four types of experiments were used to shed light on this: (1) kinetic
      measurements over a very wide range of substrate concentrations, subjected to
      detailed statistical analysis; (2) fluorescence studies of mutants in which
      phenylalanine residues were replaced by tryptophan; (3) effect of Fru-2,6-P2 and
      Fru-1,6-P2 on the exchange of subunits between wild-type and Glu-tagged
      oligomers; and (4) kinetic studies of hybrid forms of the enzyme containing
      subunits mutated at the active site residue tyrosine-244. RESULTS: The kinetic
      experiments with the wild-type enzyme indicate that the binding of Fru-1,6-P2
      induces the appearance of catalytic sites with lower affinity for substrate and
      lower catalytic activity. Binding of substrate to the high-affinity sites, but
      not to the low-affinity sites, enhances the fluorescence emission of the
      Phe219Trp mutant; the inhibitor, Fru-2,6-P2, competes with the substrate for the
      high-affinity sites. Binding of substrate to the low-affinity sites acts as a
      "stapler" that prevents dissociation of the tetramer and hence exchange of
      subunits, and results in substrate inhibition. CONCLUSIONS: Binding of the first
      substrate molecule, in one dimer of the enzyme, produces a conformational change
      at the other dimer, reducing the substrate affinity and catalytic activity of its
      subunits. GENERAL SIGNIFICANCE: Mimics of the substrate inhibition of fructose
      1,6-bisphosphatase may provide a future option for combatting both postprandial
      and fasting hyperglycemia.

PMID- 24444800
TI  - Purification of nucleic acids using isotachophoresis.
AB  - Reviewed are methods of nucleic acid (NA) extraction and sample preparation using
      an electrophoretic purification and focusing method called isotachophoresis
      (ITP). ITP requires no special surface chemistries or geometric structures, and
      can be achieved in a compact system with no moving parts. ITP is also compatible
      with a wide range of samples and lysing methods. Described are general principles
      of ITP, considerations around the application of ITP to biological samples (e.g.,
      blood, urine and saliva), ITP electrolyte design considerations for fast and
      selective NA purification, and examples of ITP compatible lysing methods. Several
      of the challenges associated with purification of NAs are presented as well as
      methods to address these. Lastly, specific examples of lysing methods and ITP
      chemistries are described for purification of NA including host and pathogenic
      DNA, pathogenic rRNA, and host micro-RNA from complex sample matrices. 

PMID- 24444801
TI  - Determination of lipophilic marine toxins in mussels. Quantification and
      confirmation criteria using high resolution mass spectrometry.
AB  - A multitoxin method has been developed for quantification and confirmation of
      lipophilic marine biotoxins in mussels by liquid chromatography coupled to high
      resolution mass spectrometry (HRMS), using an Orbitrap-Exactive HCD mass
      spectrometer. Okadaic acid (OA), yessotoxin, azaspiracid-1, gymnodimine, 13
      desmethyl spirolide C, pectenotoxin-2 and Brevetoxin B were analyzed as
      representative compounds of each lipophilic toxin group. HRMS identification and
      confirmation criteria were established. Fragment and isotope ions and ion ratios
      were studied and evaluated for confirmation purpose. In depth characterization of
      full scan and fragmentation spectrum of the main toxins were carried out.
      Accuracy (trueness and precision), linearity, calibration curve check, limit of
      quantification (LOQ) and specificity were the parameters established for the
      method validation. The validation was performed at 0.5 times the current European
      Union permitted levels. The method performed very well for the parameters
      investigated. The trueness, expressed as recovery, ranged from 80% to 94%, the
      precision, expressed as intralaboratory reproducibility, ranged from 5% to 22%
      and the LOQs range from 0.9 to 4.8pg on column. Uncertainty of the method was
      also estimated for OA, using a certified reference material. A top-down approach
      considering two main contributions: those arising from the trueness studies and
      those coming from the precision's determination, was used. An overall expanded
      uncertainty of 38% was obtained. 

PMID- 24444803
TI  - A computational model of clavicle bone formation: a mechano-biochemical
      hypothesis.
AB  - Clavicle development arises from mesenchymal cells condensed as a cord extending
      from the acromion towards the sternal primordium. First two primary ossification
      centers form, extending to develop the body of the clavicle through
      intramembranous ossification. However, at its ends this same bone also displays
      endochondral ossification. So how can the clavicle be formed by both types of
      ossification? Developmental events associated with clavicle formation have mainly
      used histological studies as supporting evidence. Nonetheless, mechanisms of
      biological events such as molecular and mechanical effects remain to be
      determined. The objective of this work was to provide a mathematical explanation
      of embryological events based on two serial phases: first formation of an
      ossified matrix by intramembranous ossification based on three factors: systemic,
      local biochemical, and mechanical factors. After this initial phase expansion of
      the ossified matrix follows with mesenchymal cell differentiation into
      chondrocytes for posterior endochondral ossification. Our model provides strong
      evidence for clavicle formation integrating molecules and mechanical stimuli
      through partial differentiation equations using finite element analysis. 

PMID- 24444802
TI  - Effect of alcohol aggregation on the retention factors of chiral solutes with an
      amylose-based sorbent: modeling and implications for the adsorption mechanism.
AB  - Various displacement models in the literature have been widely used for
      understanding the adsorption mechanisms of solutes in various chromatography
      systems. The models were used for describing the often-observed linear plots of
      the logarithms of the retention factor versus the logarithms of the polar
      modifier concentration CI(0). The slopes of such a plot was inferred to be equal
      to the number of the displaced modifier molecules upon adsorption of one solute
      molecule, and were generally found to be greater than 1. In this study, the
      retention factors of four structurally related chiral solutes, ethyl lactate
      (EL), methyl mandelate (MM), benzoin (B), and pantolactone (PL), were measured
      for the amylose tris[(S)-alpha-methylbenzylcarbamate] sorbent, or AS, as a
      function of the concentration of isopropanol (IPA) in n-hexane. With increasing
      IPA concentration CI(0), the slopes increase from less than 1, at a concentration
      range from 0.13 to 1.3M, to slightly more than 1 at higher concentrations. Such
      slopes cannot be explained by the conventional retention models. It was found
      previously for monovalent solutes that such slopes can only be explained when the
      aggregation of the mobile phase modifier, isopropyl alcohol, was accounted for. A
      new retention model is presented here, accounting for alcohol aggregation,
      multivalent solute adsorption, multivalent solute-alcohol complexation, alcohol
      adsorption, and solute intra hydrogen-bonding, which occur in these four solutes.
      The slope is found to be controlled by three key dimensionless groups, the
      fraction of the sorbent binding sites covered by IPA, the fraction of the solute
      molecules in complex form, and the fraction of the IPA molecules in aggregate
      form. The limiting slope at a very high IPA concentration is equal to the value
      of (x+y)/n, where x is the number of the solute-sorbent binding sites and y is
      the number of the alcohol molecules in the solute-alcohol complex, and n is the
      alcohol aggregation number. The model was tested with the HPLC data of two sets
      of chiral solutes, one set of new data presented here and of one set of
      literature data by Gyimesi-Forras et al. (2009), for which there is no known
      intramolecular H-bonding. For the first set of solutes, the values of the
      equilibrium constants for intramolecular hydrogen bonding were calculated from
      our previous IR data. The value of the parameter y was fixed on the basis of the
      number of the solute functional groups, IR data, and the results of DFT and MD
      simulations. The retention factors in pure hexane (k0) were found experimentally
      for EL, MM, and B; for PL they were estimated from the data. Then the values of x
      and the complexation equilibrium constants were estimated. The model fits fairly
      well our new data, and less well the more-limited literature data, for which the
      k0 values were unavailable, and the retention factors were obtained over a narrow
      range of IPA concentrations. For EL and PL, results of infrared spectroscopy,
      density functional theory, and molecular dynamics simulations indicated strong
      solute-IPA complexation, and multiple solute-sorbent binding sites, which are
      consistent with the fitting results. Hence, the new model has been shown to be
      more reliable than the previous models for estimating the numbers of the
      potential binding sites of multivalent solutes. 

PMID- 24444804
TI  - The 1,2-intercompartmental supraretinacular artery vascularized bone graft for
      scaphoid nonunion: management and clinical outcome.
AB  - PURPOSE: To evaluate the clinical outcome of 1,2-intercompartmental
      supraretinacular artery pedicled vascularized bone graft for scaphoid nonunion
      (SN). METHODS: A retrospective study was performed to evaluate patients with SN
      and treated with 1,2-intercompartmental supraretinacular artery pedicled
      vascularized bone graft between 1997 and 2010. Functional measures, quality of
      life by Short Form SF-36 questionnaire, and analysis of risk factors were
      included. RESULTS: Out of 39 patients who were eligible for the study, 11 were
      lost to follow-up. Out of the remaining 28 patients, union was achieved in 21
      (75%). The mean length of follow-up was 63 +/- 45 months. In hands with scaphoid
      union, the grip strength and the radioulnar active range of motion were less than
      the contralateral side but greater compared with patients with nonunion. Active
      extension-flexion was less compared with the noninjured hand but similar to
      patients with nonunion. Disabilities of the Arm, Shoulder and Hand (DASH) score
      decreased from 58 to 23 in dominant hands and from 46 to 13 in nondominant hands.
      Smoking was found to be a risk factor for nonunion. Patients with scaphoid union
      tended to higher scores in 8 domains of SF-36-Item Health Survey quality of life
      without significant difference. CONCLUSIONS: Surgical treatment of SN with 1,2
      intercompartmental supraretinacular artery pedicled vascularized bone graft
      provided a union rate comparable with other vascularized bone graft techniques.
      Previous scaphoid reconstruction with standard iliac crest bone graft was not
      associated with higher risk for secondary nonunion. There was an upward tendency
      seen in DASH score and quality of life after scaphoid union. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Therapeutic IV.

PMID- 24444805
TI  - Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.
AB  - Alterations in the quality, quantity, and architecture of baseline and recovery
      sleep have been shown to occur during aging. Sleep deprivation induces
      endoplasmic reticular (ER) stress and upregulates a protective signaling pathway
      termed the unfolded protein response. The effectiveness of the adaptive unfolded
      protein response is diminished by age. Previously, we showed that endogenous
      chaperone levels altered recovery sleep in Drosophila melanogaster. We now report
      that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA)
      reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA
      consolidates both baseline and recovery sleep in aging flies. The behavioral
      modifications of PBA are linked to its suppression of ER stress. PBA decreased
      splicing of X-box binding protein 1 and upregulation of phosphorylated elongation
      initiation factor 2 alpha, in flies that were subjected to sleep deprivation. We
      also demonstrate that directly activating ER stress in young flies fragments
      baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER
      stress during aging contributes to sleep consolidation and improves recovery
      sleep or sleep debt discharge. 

PMID- 24444807
TI  - Nonalcoholic fatty liver disease is a potential risk factor for cardiovascular
      diseases.

PMID- 24444808
TI  - Metal concentrations in the tissues of the hydrothermal vent mussel
      Bathymodiolus: reflection of different metal sources.
AB  - Hydrothermal vent mussels of the genus Bathymodiolus are ideally positioned for
      the use of recording hydrothermal fluxes at the hydrothermal vent sites they
      inhabit. Barium, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Pb, Sr, and U
      concentrations in tissue sections of Bathymodiolus mussels from several
      hydrothermal fields between 15 degrees N and 9 degrees S at the Mid-Atlantic
      Ridge were determined and compared to the surrounding fluids and solid substrates
      in the habitats. Elements generally enriched in hydrothermal fluids, such as Fe,
      Cu, Zn, Pb and Cd, were significantly enriched in the gills and digestive glands
      of the hydrothermal mussels. The rather small variability of Zn (and Mn) and
      positive correlation with K and earth alkaline metals may indicate a biological
      regulation of accumulation. Enrichments of Mo and U in many tissue samples
      indicate that particulate matter such as hydrothermal mineral particles from the
      plumes can play a more important role as a metal source than dissolved metals.
      Highest enrichments of Cu in mussels from the Golden Valley site indicate a
      relation to the >=400  degrees C hot heavy-metal rich fluids emanating in the
      vicinity. In contrast, mussels from the low-temperature Lilliput field are
      affected by the Fe oxyhydroxide sediment of their habitat. In a comparison of two
      different sites within the Logatchev field metal distributions in the tissues
      reflected small-scale local variations in the metal content of the fluids and the
      particulate material. 

PMID- 24444806
TI  - Interaction of APOE genotype and testosterone on episodic memory in middle-aged
      men.
AB  - Age-related changes in testosterone are believed to be a key component of the
      processes that contribute to cognitive aging in men. The APOE-epsilon4 allele may
      interact with testosterone and moderate the hormone's association with cognition.
      The goals of the present study were to examine the degree to which free
      testosterone is associated with episodic memory in a community-based sample of
      middle-aged men, and examine the potential interaction between free testosterone
      and the APOE-epsilon4 allele. Data were used from 717 participants in the Vietnam
      Era Twin Study of Aging. Average age was 55.4 years (standard deviation = 2.5).
      Significant positive associations were observed between free testosterone level
      and verbal episodic memory, as well as a significant interaction between free
      testosterone and APOE-epsilon4 status. In epsilon4 carriers free testosterone was
      positively associated with verbal episodic memory performance (story recall),
      whereas no association was observed in epsilon4 noncarriers. Results support the
      hypothesis that APOE-epsilon4 status increases susceptibility to other risk
      factors, such as low testosterone, which may ultimately contribute to cognitive
      decline or dementia.

PMID- 24444809
TI  - Alginic acid isolated from Sargassum wightii exhibits anti-inflammatory potential
      on type II collagen induced arthritis in experimental animals.
AB  - The present study evaluated the anti-inflammatory potential of alginic acid
      isolated from the brown algae Sargassum wightii in type II collagen induced
      arthritic rats, a well established arthritic model that resembles more closely to
      human rheumatoid arthritis in its clinical, pathological, immunological and
      histological aspects. Type II collagen induced arthritic rats showed increased
      activities of inflammatory marker enzymes like cycloxygenase-2 (COX-2),
      lipoxygenase (5-LOX), xanthine oxidase (XO) and myeloperoxidase (MPO) along with
      increased concentration of rheumatoid factor (RF), ceruloplasmin and C-reactive
      protein (CRP). Treatment with alginic acid significantly reduced the activities
      of COX-2 and 5-LOX along with reduction in MPO, XO, RF and CRP. Alginic acid
      treatment reverted to the altered levels of hematological parameters like RBC
      count, WBC count and ESR in arthritic rats. Concentrations of proinflammatory
      cytokines like IL-1 beta, TNF alpha and IL-6 were significantly higher in
      arthritic rats which were reduced on treatment with alginic acid. Increased
      activities of lysosomal enzymes that manifest the systemic damage during
      arthritis were significantly reduced by the treatment with alginic acid which
      indicates the reduction in the rupture and degradation of connective tissue.
      Histopathology of knee joint tissues showed that extensive bone degradation and
      synovial hyperplasia along with infiltrating cells and treatment with alginic
      acid reversed the histopathological changes which indicate the protective
      potential of alginic acid in rheumatoid arthritis. 

PMID- 24444810
TI  - Mechanisms of myocardial infarction without obstructive coronary artery disease.
AB  - Angiography in patients with myocardial infarction (MI) most commonly reveals one
      or more significantly narrowed coronary arteries, but a substantial minority of
      patients with spontaneous MI have no obstructive coronary artery disease (CAD) at
      angiography. This review summarizes evidence for the most commonly hypothesized
      mechanisms, including plaque disruption, plaque erosion, vasospasm, embolism, and
      spontaneous coronary dissection. In addition, tako-tsubo syndrome and myocarditis
      are discussed. The best treatment of MI without obstructive CAD is likely to
      differ substantially based on the underlying cause. Additional mechanistic
      research is needed to facilitate the design of research studies aimed at
      documenting the best treatments for these patients, numbering as many as 225,000
      per year in the US. 

PMID- 24444811
TI  - Stochastic population dynamics in a Markovian environment implies Taylor's power
      law of fluctuation scaling.
AB  - Taylor's power law of fluctuation scaling (TL) states that for population
      density, population abundance, biomass density, biomass abundance, cell mass,
      protein copy number, or any other nonnegative-valued random variable in which the
      mean and the variance are positive, variance=a(mean)(b),a>0, or equivalently log
      variance=loga+b*log mean. Many empirical examples and practical applications of
      TL are known, but understanding of TL's origins and interpretations remains
      incomplete. We show here that, as time becomes large, TL arises from
      multiplicative population growth in which successive random factors are chosen by
      a Markov chain. We give exact formulas for a and b in terms of the Markov
      transition matrix and the values of the successive multiplicative factors. In
      this model, the mean and variance asymptotically increase exponentially if and
      only if b>2 and asymptotically decrease exponentially if and only if b<2. 

PMID- 24444812
TI  - Incipient plasticity in 4H-SiC during quasistatic nanoindentation.
AB  - Silicon carbide (SiC) is an important orthopedic material due to its inert nature
      and superior mechanical and tribological properties. Some of the potential
      applications of silicon carbide include coating for stents to enhance
      hemocompatibility, coating for prosthetic-bearing surfaces and uncemented joint
      prosthetics. This study is the first to explore nanomechanical response of single
      crystal 4H-SiC through quasistatic nanoindentation. Displacement controlled
      quasistatic nanoindentation experiments were performed on a single crystal 4H-SiC
      specimen using a blunt Berkovich indenter (300nm tip radius) at extremely fine
      indentation depths of 5nm, 10nm, 12nm, 25nm, 30nm and 50nm. Load-displacement
      curve obtained from the indentation experiments showed yielding or incipient
      plasticity in 4H-SiC typically at a shear stress of about 21GPa (~an indentation
      depth of 33.8nm) through a pop-in event. An interesting observation was that the
      residual depth of indent showed three distinct patterns: (i) positive depth
      hysteresis above 33nm, (ii) no depth hysteresis at 12nm, and (iii) negative depth
      hysteresis below 12nm. This contrasting depth hysteresis phenomenon is
      hypothesized to originate due to the existence of compressive residual stresses
      (upto 143MPa) induced in the specimen by the polishing process prior to the
      nanoindentation. 

PMID- 24444813
TI  - Is global access to infertility care realistic? The Walking Egg Project.
AB  - Until very recently, the problem of infertility in developing countries has been
      ignored at all levels of healthcare management. Because many preventable or
      treatable diseases still claim millions of lives, and due to limited resources,
      provision of infertility care is not on the resource allocation agenda at all,
      prevention of sexually transmitted diseases remaining the number one priority.
      Tubal infertility due to sexually transmitted diseases, unsafe abortion and post
      partum pelvic infections is the main cause of infertility. Most cases are only
      treatable with assisted reproduction technology, which are either unavailable or
      too costly. In December 2007, an expert meeting was organized in Arusha, Tanzania
      by the Walking Egg non-profit organization in co-operation with ESHRE. The
      meeting was the start of a global project aimed at increasing diagnostic and
      therapeutic options for childless couples in resource-poor countries. From the
      start, the Walking Egg Project has approached this problem in a multidisciplinary
      and global manner. It gathers medical, social, ethical, epidemiological,
      juridical and economic scientists to discuss and work together towards its goal.
      The final objective of the Walking Egg Project is the implementation of
      infertility services in many developing countries, preferably integrated in
      existing family planning and mother care services. 

PMID- 24444814
TI  - Vitrification is not superior to rapid freezing of normozoospermic spermatozoa:
      effects on sperm parameters, DNA fragmentation and hyaluronan binding.
AB  - Human sperm vitrification is a new cryopreservation method. This study compared
      the effects of rapid freezing and vitrification on various sperm parameters,
      hyaluronan-binding assay and DNA fragmentation and assessed the impact of
      cryoprotectant agents (CPA) with vitrification. A total of 30 normo-ejaculates
      were prepared by swim up and the motile sperm fraction was divided into four:
      fresh (control), rapid freezing, and two vitrification groups (a, lacking CPA; b,
      with CPA). For rapid freezing, a cryovial of sperm suspension was held just above
      the liquid nitrogen surface, and for vitrification, 30MUl suspension was dropped
      directly into liquid nitrogen. Sperm parameters, including motility, viability
      and morphology, declined after cryopreservation in both groups. DNA fragmentation
      was not significantly higher in the vitrification (15.7+/-4.4%) or rapid freezing
      (16.6+/-5.6%) groups when compared with controls (11.6+/-4.5%). The rates of
      hyaluronan binding were similar between the control and cryopreserved groups.
      Moreover, addition of CPA for vitrification had a neutral effect on rates of
      sperm recovery. In conclusion, vitrification has great potential for human sperm
      cryopreservation and does not require CPA, with its possible toxicity. However,
      it is not superior to rapid cryopreservation regarding sperm recovery rate in
      normozoospermia. Human sperm vitrification is a new cryopreservation method that
      has been introduced recently. This study compared the effects of rapid freezing
      with vitrification on rates of sperm parameters, hyaluronan-binding assay and DNA
      fragmentation after thawing/warming and assessed the impact of cryoprotectant
      agent (CPA) on vitrification. The study was performed on 30 ejaculates prepared
      using the swim-up technique. Each motile sperm suspension was divided into four:
      control (fresh); rapid freezing; and two vitrification groups (a, lacking CPA; b,
      with CPA). For rapid freezing, a cryovial of sperm suspension was held above the
      surface of liquid nitrogen. For vitrification, 30MUl sperm suspension was dropped
      into liquid nitrogen directly. The rates of progressive motility (86.6+/-5.9%)
      and viability (95.8+/-3.9%) in controls declined significantly, to 40.0+/-13.0%
      and 63.2+/-7.7% for rapid freezing and 41.9+/-10.3% and 64.4+/-10.0% for
      vitrification, respectively. Normal sperm morphology was also significantly
      decreased after cryopreservation in all groups. DNA fragmentation was higher with
      rapid freezing compared with fresh controls (16.6+/-5.6% vs. 11.6+/-4.5%,
      P=0.01), but DNA fragmentation did not increase significantly in vitrified
      samples (15.7+/-4.4%). The rates of hyaluronan binding were similar between the
      control and cryopreserved groups. Moreover, addition of CPA for vitrification had
      a neutral effect on rates of sperm recovery. In conclusion, vitrification has
      great potential for human sperm cryopreservation and does not require CPA, with
      its possible toxicity. However, it is not superior to rapid cryopreservation
      regarding sperm recovery rate in normozoospermia. 

PMID- 24444815
TI  - Behaviour of cytoplasmic organelles and cytoskeleton during oocyte maturation.
AB  - Assisted reproduction technology (ART) has become an attractive option for
      infertility treatment and holds tremendous promise. However, at present, there is
      still room for improvement in its success rates. Oocyte maturation is a process
      by which the oocyte becomes competent for fertilization and subsequent embryo
      development. To better understand the mechanism underlying oocyte maturation and
      for the future improvement of assisted reproduction technology, this review
      focuses on the complex processes of cytoplasmic organelles and the dynamic
      alterations of the cytoskeleton that occur during oocyte maturation. Ovarian
      stimulation and in-vitro maturation are the major techniques used in assisted
      reproduction technology and their influence on the organelles of oocytes is also
      discussed. Since the first birth by assisted reproduction treatment was achieved
      in 1978, numerous techniques involved in assisted reproduction have been
      developed and have become attractive options for infertility treatment. However,
      the unsatisfactory success rate remains as a main challenge. Oocyte maturation is
      a process by which the oocyte becomes competent for fertilization and subsequent
      embryo development. Oocyte maturation includes both nuclear and cytoplasmic
      maturation. Nuclear maturation primarily involves chromosomal segregation, which
      has been well studied, whereas cytoplasmic maturation involves a series of
      complicated processes, and there are still many parts of this process that remain
      controversial. Ovarian stimulation and in-vitro maturation (IVM) are the major
      techniques of assisted reproduction. The effect of ovarian stimulation or IVM on
      the behaviour of cell organelles of the oocyte has been postulated as the reason
      for the reduced developmental potential of in-vitro-produced embryos. To further
      understanding of the mechanism of oocyte maturation and future improvement of
      assisted reproduction treatment, the complex events of cytoplasmic organelles and
      the cytoskeleton that occur during oocyte maturation and the influence of ovarian
      stimulation and IVM on these organelles are described in this review. 

PMID- 24444817
TI  - MoS2 nanocube structures as catalysts for electrochemical H2 evolution from
      acidic aqueous solutions.
AB  - Core-shell PMMA-Au nanocube structures made by a combination of nanoimprint
      lithography and sidewall deposition were used as template for electrodeposition
      of MoS2, Ni, and Pt. Linear sweep voltammetry experiments obtained in an aqueous
      solution containing 0.29 M H2SO4 (pH 0.24) showed that the onset potential of the
      core-shell-shell PMMA-Au-MoS2 nanocube electrode for the hydrogen evolution
      reaction (HER) was shifted to the positive direction (i.e., requiring a lower
      overpotential) by 20-40 mV compared to planar MoS2 films. This indicates that the
      nanocube electrodes have a significantly increased HER activity, which is
      probably because of a higher density of catalytically active edge sites available
      at the nanocube surface. It was also found that the HER activity initially
      increased with increasing MoS2 deposition time, but decreased after deposition
      for 60 min because the edges of the nanocubes became rounded, thereby decreasing
      the number of active edge sites. By depositing Ni and Pt on top of PMMA-Au
      nanocubes, it was shown that this method can also be used for the synthesis of
      nanocube structures with varying compositions. 

PMID- 24444816
TI  - Aneuploidy is a key causal factor of delays in blastulation: author response to
      'A cautionary note against aneuploidy risk assessment using time-lapse imaging'.
AB  - In a previous paper, we had reported use of time-lapse monitoring to develop an
      aneuploidy risk classification model after identifying significant
      periblastulation delays in aneuploid embryos compared with euploid embryos. The
      model was validated subsequently in a second paper by retrospective assessment of
      transferred blastocysts that had also undergone time-lapse monitoring in which
      clinical pregnancy or live birth outcomes were established. A significant
      difference was seen for both outcome measures between embryos classified as low
      and medium risk by the model. Here we respond to the commentary entitled 'A
      cautionary note against embryo aneuploidy risk assessment using time-lapse
      imaging', which presented a case for our conclusions being unsound on the basis
      that maternal age, rather than aneuploidy, might be the cause of the
      developmental delays observed. We demonstrate that this is not the case and
      strengthen the argument that ploidy is a key factor influencing morphokinetics of
      blastulation. We also describe why the arguments made in the commentary based on
      comparisons between static standard observations and timings of the
      preimplantation embryo compared with those obtained from dynamic or time-lapse
      methodologies are inexact. 

PMID- 24444818
TI  - T-lymphocyte-rich thymoma and myasthenia gravis in a Siberian tiger (Panthera
      tigris altaica).
AB  - A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented
      with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of
      progressive muscle wasting. Following humane destruction, post-mortem examination
      revealed a large multilobulated mass in the cranial mediastinum, which was
      diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry.
      Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l)
      confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are
      reported rarely in wild carnivores, but when detected they appear to be similar
      in morphology to those seen in domestic carnivores and may also be accompanied by
      paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger
      were consistent with those reported in cats and dogs and the condition is
      proposed as an important differential diagnosis for generalized weakness in
      captive Felidae.

PMID- 24444819
TI  - Expression of PGP 9.5 by enteric neurons in horses and donkeys with and without
      intestinal disease.
AB  - Intestinal motility disorders are an important problem in horses and donkeys and
      this study was carried out in order to evaluate the enteric neurons in animals
      with and without intestinal disease. Surplus intestinal tissue samples were
      collected from 28 horses undergoing exploratory laparotomy for colic. In
      addition, surplus intestinal samples from 17 control horses were collected
      immediately following humane destruction for clinical conditions not relating to
      the intestinal tract. Similar samples were also collected during routine post
      mortem examinations from 12 aged donkeys; six animals were humanely destroyed for
      conditions related to the intestinal tract, while the remaining six were humanely
      destroyed for other reasons including dental and orthopaedic diseases. Tissue
      samples were fixed in formalin and immunohistochemical labelling was performed
      targeting the enteric neurons using a polyclonal antibody specific for the
      neuronal marker PGP 9.5. The distribution and density of neuronal networks were
      assessed qualitatively and semiquantitatively. There was strong PGP 9.5
      expression in both the horse and donkey samples and labelling was detected
      throughout the tissue sections. In both species, PGP 9.5-immunoreactive nerve
      fibres were detected in all layers of the intestinal tract, both in large and
      small intestinal samples. Networks of enteric neurons were present in the donkey
      with a similar distribution to that seen in the horse. There was no demonstrable
      difference in enteric neuronal density and distribution in the groups of animals
      with intestinal disease compared with those without, apart from two (out of 28)
      horses with intestinal disease that showed a marked reduction in PGP 9.5
      immunoreactivity. Apart from these two animals, this total cohort analysis
      differs from some previously observed findings in horses with intestinal disease
      and may therefore reflect the different pathophysiological processes occurring in
      varying intestinal conditions resulting in colic both in the donkey and the
      horse. 

PMID- 24444820
TI  - Mismatch repair protein expression in 1049 endometrial carcinomas, associations
      with body mass index, and other clinicopathologic variables.
AB  - OBJECTIVE: Links between obesity, with its attendant estrogen abnormalities, and
      the endometrial carcinoma (EC) DNA Mismatch Repair Protein (MMR) system have
      recently been proposed. We investigated relationships between body mass index
      (BMI) and clinicopathological correlates including MMR expression in a large
      single institution EC cohort. METHODS: Clinical and pathological databases from
      2007 to 2012 were used to identify consecutive hysterectomy specimens with EC.
      Univariate and multivariate analyses were used to explore relationships between
      BMI, age, stage, tumor type and immunohistochemical results for MLH1, PMS2, MSH2
      and MSH6. RESULTS: 1049 EC were identified. Overall, BMI was higher amongst women
      with normal MMR (p=0.002). However, when stratified by age and specific MMR,
      statistically significant differences localized exclusively to women <50years old
      with loss of MSH2 and/or MSH6 (p=0.003 and p=0.005 respectively). Higher BMI
      correlated with endometrioid FIGO 1 and 2 tumors (p<0.001) and with stage 1a
      (p<0.001). Conversely, MMR abnormalities did not show significant associations
      with stage (p=0.302) or histologic grade (p=0.097). CONCLUSIONS: BMI showed
      statistically significant associations with MMR expression, tumor grade and stage
      amongst 1049 consecutive EC. Obesity correlates with lower grade and stage EC. A
      link between BMI and maintenance of the MMR system is not supported by our data
      because the only statistically significant association occurred in women <50years
      old with MSH2 and/or MSH6 abnormalities where Lynch syndrome related cases are
      expected to cluster.

PMID- 24444821
TI  - Guanidine platinum(II) complexes: synthesis, in vitro antitumor activity, and DNA
      interactions.
AB  - The novel guanidine compounds trans-[Pt(NH2Me)2{NH=C(NHMe)NR}2](Cl)2 (R=NEt2 [7],
      NC5H10 [8]) (trans-7,8) were synthesized by the nucleophilic addition of
      methylamine to dialkylcyanamide ligands of the push-pull nitrile complexes trans
      [PtCl2(RCN)2] (R=NEt2, NC5H10). In vitro cytotoxicity tests conducted for the
      entire series of the guanidine complexes, i.e. trans-7,8, the neutral cis- or
      trans-[PtCl2{NH=C(NH2)R}2] (cis-1-3 and trans-1-3) and the cationic cis- or trans
      [Pt(NH3)2{NH=C(NH2)R}2](Cl)2 (cis-4-6 and trans-4-6) (R=NMe2 [1,4], NEt2 [2,5],
      NC5H10 [3,6]) in two human cancer cell lines, CH1 (ovarian carcinoma) and SW480
      (colon cancer), confirmed that the cytotoxicity of several trans-configured
      (trans-3,6) complexes is higher than that of cis-congeners (cis-3,6). Cellular
      platinum levels were analyzed by inductively coupled plasma mass spectrometry
      upon treatment of SW480 cells, revealing a dependence of cellular accumulation on
      the geometrical isomerism and the steric hindrance of the variable substituent R
      on the guanidine ligand. DNA interactions of selected guanidine complexes were
      studied in order to find hints for the possible reasons for their different
      activities. Changes induced to the electrophoretic mobility of a dsDNA plasmid
      confirmed the potency of the guanidine complexes (e.g. trans-1,3,5,6 and cis
      1,3,4) to significantly alter DNA secondary structure, indicating DNA as a
      possible critical target of these compounds. 

PMID- 24444822
TI  - Altered expression of neuropeptide Y, Y1 and Y2 receptors, but not Y5 receptor,
      within hippocampus and temporal lobe cortex of tremor rats.
AB  - As an endogenous inhibitor of glutamate-mediated synaptic transmission in
      mammalian central nervous system, neuropeptide Y (NPY) plays a crucial role in
      regulating homeostasis of neuron excitability. Loss of balance between excitatory
      and inhibitory neurotransmission is thought to be a chief mechanism of
      epileptogenesis. The abnormal expression of NPY and its receptors observed
      following seizures have been demonstrated to be related to the production of
      epilepsy. The tremor rat (TRM) is a hereditary epileptic animal model. So far,
      there is no report concerning whether NPY and its receptors may be involved in
      TRM pathogenesis. In this study, we focused on the expression of NPY and its
      three receptor subtypes: Y1R, Y2R and Y5R in the TRM brain. We first found the
      expression of NPY in TRM hippocampus and temporal lobe cortex was increased
      compared with control (Wistar) rats. The mRNA and protein expression of Y1R was
      down-regulated in hippocampus but up-regulated in temporal lobe cortex, whereas
      Y2R expression was significantly increased in both areas. There was no
      significant change of Y5R expression in either area. The immunohistochemistry
      data showed that Y1R, Y2R, Y5R were present throughout CA1, CA3, dentate gyrus
      (DG) and the entorhinal cortex which is included in the temporal lobe cortex of
      TRM. In conclusion, our results showed the altered expression of NPY, Y1R and Y2R
      but not Y5R in hippocampus and temporal lobe cortex of TRM brain. This abnormal
      expression may be associated with the generation of epileptiform activity and
      provide a candidate target for treatment of genetic epilepsy. 

PMID- 24444823
TI  - Effect of oxytocin on the behavioral activity in the behavioral despair
      depression rat model.
AB  - Oxytocin (OXT), a nonapeptide posterior hormone of the pituitary, is mainly
      synthesized and secreted in the hypothalamic paraventricular nucleus (PVN) and
      supraoptic nucleus (SON). The present study was to investigate in which level,
      brain or periphery, OXT effecting on the behavioral activity in the behavioral
      despair depression rat model. The results showed that (1) either the forced
      swimming or the tail suspension significantly increased OXT concentration in the
      brain (PVN, SON, frontal cortex, hippocampus, amygdala, lumbar spinal cord) and
      in the periphery (posterior pituitary and serum); (2) intraventricular injection
      (icv) of OXT decreased the animal immobility time, whereas OXT receptor
      antagonist-desGly-NH2, d(CH2)5[D-Tyr2, Thr-sup-4]OV (icv) increased the animal
      immobility time in a dose-dependent manner in forced swimming test (FST) and in
      tail suspension test (TST); (3) neither OXT nor OXT receptor antagonist
      (intravenous injection) influenced the animal immobility time in FST and in TST.
      OXT levels were increased in several areas of the brain and in the periphery
      following the behavioral despair, one stressor, yet pre-treatment with OXT
      appeared to be beneficial in term of reducing immobility time. The data suggested
      that behavioral despair could enhance OXT synthesis and secretion not only in the
      brain but also in the periphery, and OXT in the brain rather than the periphery
      played a role in the behavioral despair depression. 

PMID- 24444824
TI  - Construction of a Boolean model of gene and protein regulatory network with
      memory.
AB  - A Boolean model of gene and protein regulatory network with memory (GPBN) has
      recently attracted interest as a generalization of original random Boolean
      networks (BNs) for genetic and cellular networks. It is better suited to describe
      experimental data from the time-course microarray. Addressing construction
      problems in GPBNs may lead to a better understanding of the intrinsic dynamics in
      biological systems. Using the technique of the semi-tensor product (STP) of
      matrices, the dynamics of a GPBN can be expressed in an algebraic form and the
      attractors can be calculated. This paper investigates the issue of construction
      of GPBNs from prescribed attractors. Based on a rigorous theoretical analysis,
      some algebraic formulae and a computationally feasible algorithm are obtained to
      construct the least in-degree model with prescribed attractors. Illustrative
      examples are presented to show the validity of the theoretical results and the
      proposed algorithm. 

PMID- 24444825
TI  - Molecular characterization, immune responsive expression and functional analysis
      of QM, a putative tumor suppressor gene from the Pacific white shrimp,
      Litopenaeus vannamei.
AB  - The QM, firstly identified as a putative tumor suppressor gene from human, has
      been confirmed to possess varieties of functions in a range of organisms. In the
      present study, the cDNA that encodes a 220-amino-acid QM protein with calculated
      molecular mass of 25.5 kDa and isoelectric point of 10.07 was characterized from
      the Pacific white shrimp Litopenaeus vannamei. Analysis of the deduced amino acid
      sequence of LvQM revealed that it contained a series of conserved functional
      motifs. Quantitative real-time PCR (qRT-PCR) results showed that the transcript
      of LvQM was extensively distributed in the tissues under investigation and most
      highly expressed in gill. After challenged with Vibrio anguillarum, the LvQM
      transcripts were significantly increased (P < 0.05) both in hepatopancreas and
      hemocytes in the early experimental phase. When LvQM was knocked down by RNA
      interference (RNAi), the transcript of prophenoloxidase (proPO) and the
      phenoloxidase activity (PO) in shrimp hemolymph were dramatically decreased,
      while the mortality was significantly increased. Furthermore, the recombinant
      LvQM protein (rLvQM) was successfully expressed in Escherichia coli BL21 (DE3)
      pLysS. Injecting the purified rLvQM mixed with V. anguillarum markedly increased
      the clearance rate of bacteria and PO activity in the shrimp hemolymph. Hence, we
      conclude that LvQM was involved in the host defense of L. vannamei, probably as a
      positive regulator to phenoloxidase activity. 

PMID- 24444826
TI  - Effect of MontanideTM IMS 1312 VG adjuvant on efficacy of Yersinia ruckeri
      vaccine in rainbow trout (Oncorhynchus mykiss).
AB  - The efficacy of immersion vaccination Yersinia ruckeri bacterin containing
      MontanideTM IMS 1312 VG was evaluated in 100-120 g rainbow trout against
      yersiniosis. Healthy fish were vaccinated by immersion vaccination with
      inactivated whole cells (1 * 10(8) cells/ml) of a virulent strain of Y. ruckeri
      biotype I with and without Montanide (1:1; Montanide/antigen) for 2 min at 12-14 
      degrees C. Control group was immersed in sterile PBS. Leukocyte counts, serum
      lysozyme assay, alternative hemolytic complement (ACH50) assay, antibody
      titration and relative percent survival (RPS) were measured on 2-10 weeks post
      immunization. No significant difference was seen in leucocyte population of trout
      immunized either with Y. ruckeri antigen or Y. ruckeri antigen containing
      Montanide (P > 0.05), while leucocyte and heterophil populations in control group
      were significantly lower and higher, respectively, than both immunized groups (P
      < 0.05). In addition, there was no significant difference in lymphocyte
      population of trout immunized either with Y. ruckeri antigen or Y. ruckeri
      antigen containing Montanide (P > 0.05), while lymphocyte population in control
      group was significantly lower than both immunized groups (P < 0.05). Lysozyme
      activity in immunized fish with Y. ruckeri containing Montanide was higher than
      the immunized fish with Y. ruckeri antigen alone during 8 weeks post-immunization
      ((P < 0.05). Also, level of lysozyme in control fish was generally lower than
      both immunized groups (P < 0.05). The level of ACH50 between both immunized
      groups was insignificant (P > 0.05) but these were significantly higher than
      control group through the experiment (P < 0.05). The lowest anti-Y. ruckeri
      antibody titers in both immersion vaccination groups were significantly higher
      through 2-8 weeks post-vaccination compared to the control group (P < 0.05). In
      the group immersion vaccinated with Y. ruckeri bacterin plus Montanide the titers
      2-8 weeks post-vaccination were significantly higher the titer in the immersion
      vaccinated with Y. ruckeri bacterin (P < 0.05). Fish vaccinated with antigen
      without Montanide resulted in RPS of 80-82% on 2-10 weeks post-vaccination, while
      those for antigen containing montanide gave RPSs of 93.8-100% 2-10 weeks post
      immunization (P < 0.05). 

PMID- 24444827
TI  - Effects of intravenous administration of umbilical cord blood CD34(+) cells in a
      mouse model of neonatal stroke.
AB  - Neonatal stroke occurs in approximately 1/4000 live births and results in life
      long neurological impairments: e.g., cerebral palsy. Currently, there is no
      evidence-based specific treatment for neonates with stroke. Several studies have
      reported the benefits of umbilical cord blood (UCB) cell treatment in rodent
      models of neonatal brain injury. However, all of the studies examined the effects
      of administering either the UCB mononuclear cell fraction or UCB-derived
      mesenchymal stem cells in neonatal rat models. The objective of this study was to
      examine the effects of human UCB CD34(+) cells (hematopoietic stem
      cell/endothelial progenitor cells) in a mouse model of neonatal stroke, which we
      recently developed. On postnatal day 12, immunocompromized (SCID) mice underwent
      permanent occlusion of the left middle cerebral artery (MCAO). Forty-eight hours
      after MCAO, human UCB CD34(+) cells (1*10(5)cells) were injected intravenously
      into the mice. The area in which cerebral blood flow (CBF) was maintained was
      temporarily larger in the cell-treated group than in the phosphate-buffered
      saline (PBS)-treated group at 24h after treatment. With cell treatment, the
      percent loss of ipsilateral hemispheric volume was significantly ameliorated
      (21.5+/-1.9%) compared with the PBS group (25.6+/-5.1%) when assessed at 7weeks
      after MCAO. The cell-treated group did not exhibit significant differences from
      the PBS group in either rotarod (238+/-46s in the sham-surgery group, 175+/-49s
      in the PBS group, 203+/-54s in the cell-treated group) or open-field tests. The
      intravenous administration of human UCB CD34(+) cells modestly reduced
      histological ischemic brain damage after neonatal stroke in mice, with a
      transient augmentation of CBF in the peri-infarct area. 

PMID- 24444829
TI  - Soft-diet feeding after weaning affects behavior in mice: Potential increase in
      vulnerability to mental disorders.
AB  - Mastication is one of the most important oral functions, and the period during
      which mastication is acquired overlaps with the term of rapid development and
      maturation of the neural systems. In particular, the acquisition period after
      weaning is related to the potential onset of mental disorders. However, the roles
      of mastication during this period for brain development remain largely unknown.
      Therefore, we used a series of standard behavioral analyses, assessment of
      hippocampal cell proliferation, and the expression of brain-derived neurotrophic
      factor (BDNF), TrkB, and Akt1 in the hippocampus and frontal cortex of mice to
      investigate the effects of post-weaning mastication on brain function. We fed 21
      day-old C57BL6/J male mice either a hard or a soft diet for 4weeks and conducted
      a series of standard behavioral tests from 7weeks of age. Further, histological
      analysis with bromodeoxyuridine was performed to compare hippocampal cell
      proliferation at 7 and 14weeks of age. Real-time polymerase chain reaction was
      performed to compare BDNF, TrkB, and Akt1 expression in the hippocampus and
      frontal cortex of 14-week-old mice. Compared to mice fed a hard diet (HDM), soft
      diet mice (SDM) showed behavioral impairments, including decreased home cage
      activity, increased open field test activity, and deficits in prepulse
      inhibition. These results were similar to those observed in mouse models of
      schizophrenia. However, no effects were observed on anxiety-like behaviors or
      memory/learning tests. Compared to HDM, SDM showed significantly decreased
      hippocampal cell proliferation and hippocampal BDNF and Akt1 gene expression at
      14weeks of age. A soft diet after weaning may have resulted in histological and
      molecular changes in the hippocampus and influenced outcomes of behavioral tests
      related to mental disorders. Our findings suggest that soft-diet feeding after
      weaning may affect both physical and mental development of mice, and may increase
      vulnerability to mental disorders. 

PMID- 24444828
TI  - alpha4betadelta-GABAARs in the hippocampal CA1 as a biomarker for resilience to
      activity-based anorexia.
AB  - Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating
      and an intense fear of gaining weight. Most individuals with AN are females,
      diagnosed first during adolescence, 40-80% of whom exhibit excessive exercise,
      and an equally high number with a history of anxiety disorder. We sought to
      determine the cellular basis for individual differences in AN vulnerability by
      using an animal model, activity-based anorexia (ABA), that is induced by
      combining food restriction (FR) with access to a running wheel that allows
      voluntary exercise. Previously, we showed that by the fourth day of FR, the ABA
      group of adolescent female rats exhibit >500% greater levels of non-synaptic
      alpha4betadelta-GABAARs at the plasma membrane of hippocampal CA1 pyramidal cell
      spines, relative to the levels found in age-matched controls that are not FR and
      without wheel access. Here, we show that the ABA group exhibits individual
      differences in body weight loss, with some losing nearly 30%, while others lose
      only 15%. The individual differences in weight loss are ascribable to individual
      differences in wheel activity that both precedes and concurs with days of FR.
      Moreover, the increase in activity during FR correlates strongly and negatively
      with alpha4betadelta-GABAAR levels (R=-0.9, p<0.01). This negative correlation is
      evident within 2days of FR, before body weight loss approaches life-threatening
      levels for any individual. These findings suggest that increased shunting
      inhibition by alpha4betadelta-GABAARs in spines of CA1 pyramidal neurons may
      participate in the protection against the ABA-inducing environmental factors of
      severe weight loss by suppressing excitability of the CA1 pyramidal neurons
      which, in turn, is related indirectly to suppression of excessive exercise. The
      data also indicate that, although exercise has many health benefits, it can be
      maladaptive to individuals with low levels of alpha4betadelta-GABAARs in the CA1,
      particularly when combined with FR. 

PMID- 24444830
TI  - Screening for type 2 diabetes and pre-diabetes in general practice: a descriptive
      study of Maltese practices.
AB  - OBJECTIVE: The aim of this research study was to ascertain the awareness of
      Maltese family doctors to the prevalence and significance of impaired glucose
      regulation and early diagnosis of type 2 diabetes and whether practices were
      influenced by employment status, post-graduate training in diabetes or years
      since graduation. METHODS: A specially constructed questionnaire was distributed
      by mail to all the 298 family doctors listed as Specialists in Family Medicine in
      the Maltese Medical Council register. Participants had to be practising family
      medicine in Malta. Results were analysed using SPSS 20.0 aiming for a
      significance criterion of 0.05 and a power of 80%. RESULTS: Valid replies were
      received from 154 GPs (51.7%). 93.2% claimed to offer their patients some form of
      screening. Screening levels reached up to 95.9% in the presence of specific risk
      factors (e.g., high previous HbA1c levels) but fell to between 46.2% and 58.7% in
      patients over 50, the physically inactive and those who suffer from polycystic
      ovarian syndrome. Screening using capillary glucose is widespread (70.8%) as
      opposed to the oral glucose tolerance test (23.4%). Results also show a high use
      of urinalysis in screening (53.2%) and a paradoxical lack of use of HbA1c in
      screening by young doctors and by those with recent extra training in diabetes.
      CONCLUSIONS: The need for a structured screening programme in Malta and its
      viability need to be evaluated by further studies. Educational support to GPs
      together with logistic support for GPs needs to be improved.

PMID- 24444831
TI  - Succinonitrile as a corrosion inhibitor of copper current collectors for
      overdischarge protection of lithium ion batteries.
AB  - Succinonitrile (SN) is investigated as an electrolyte additive for copper
      corrosion inhibition to provide overdischarge (OD) protection to lithium ion
      batteries (LIBs). The anodic Cu corrosion, occurring above 3.5 V (vs Li/Li(+)) in
      conventional LIB electrolytes, is suppressed until a voltage of 4.5 V is reached
      in the presence of SN. The corrosion inhibition by SN is ascribed to the
      formation of an SN-induced passive layer, which spontaneously develops on the
      copper surface during the first anodic scan. The passive layer is composed mainly
      of Cu(SN)2PF6 units, which is evidenced by Raman spectroscopy and electrochemical
      quartz crystal microbalance measurements. The effects of the SN additive on OD
      protection are confirmed by using 750 mAh pouch-type full cells of LiCoO2 and
      graphite with lithium metal as a reference electrode. Addition of SN completely
      prevents corrosion of the copper current collector in the full cell
      configuration, thereby tuning the LIB chemistry to be inherently immune to the OD
      abuses. 

PMID- 24444832
TI  - Relationships between skinfold thickness and electromyographic and
      mechanomyographic amplitude recorded during voluntary and non-voluntary muscle
      actions.
AB  - INTRODUCTION: The purpose of this study was to examine possible correlations
      between skinfold thicknesses and the a terms from the log-transformed
      electromyographic (EMGRMS) and mechanomyographic amplitude (MMGRMS)-force
      relationships, EMG M-Waves, and MMG gross lateral movements (GLM). METHODS: Forty
      healthy subjects performed a 6-s isometric ramp contraction from 5% to 85% of
      their maximal voluntary contraction with EMG and MMG sensors placed on the vastus
      lateralis (VL) and rectus femoris (RF). A single electrical stimulus was applied
      to the femoral nerve to record the EMG M-waves and MMG GLMs. Skinfold thickness
      was assessed at the site of each electrode. Pearson's product correlation
      coefficients were calculated comparing skinfold thicknesses with the a terms from
      the log-transformed EMGRMS-and MMGRMS-force relationships, EMG M-waves, and MMG
      GLMs. RESULTS: There were no significant cor1relations (p>0.05) between the a
      terms and skinfold thicknesses for the RF and VL from the EMGRMS and MMGRMS-force
      relationships. However, there were significant correlations (p<0.05) between
      skinfold thicknesses and the EMG M-waves and MMG GLMs for the RF (r=-0.521, 
      0.376) and VL (r=-0.479, -0.484). DISCUSSION: Relationships were only present
      between skinfold thickness and the amplitudes of the EMG and MMG signals during
      the non-voluntary muscle actions.

PMID- 24444833
TI  - The effect of children on depression in old age.
AB  - This article investigates the causal relationship between the number of
      biological children and mental health of elderly Europeans. Specifically, we ask
      whether additional children improve or threaten parents' mental health status.
      The identification of causal effects draws on two natural experiments that
      exogenously increase the number of children: multiple births and the sex
      composition of the first two children. This setup allows us to identify the
      effect of expected and desired as well as the effect of unexpected additional
      children on mental health. For women, we find conflicting evidence regarding the
      effect of additional children on mental health, and we only find a negative
      effect of having additional children on mental health using multiple birth at the
      second pregnancy as instrument. Thus, it takes a rare and somewhat particular
      situation to uncover the negative effect. There is no evidence for a causal
      effect of additional children on the probability to suffer from depression for
      elder men. 

PMID- 24444834
TI  - Subjective financial well-being, income and health inequalities in mid and later
      life in Britain.
AB  - The relationship between health and income is well established, but the link
      between subjective financial well-being and self-reported health has been
      relatively ignored. This study investigates the relationship between income,
      subjective financial well-being and health in mid-life and later life in Britain.
      Analysis of the General Household Survey for 2006 examined these relationships at
      ages 45-64 (n = 4639) and 65 and over (n = 3104). Logistic regression analysis
      was used to adjust for income and other socio-economic factors associated with
      self-reported health. Both income and subjective financial well-being are
      independently associated with health in mid-life; those with lower incomes and
      greater subjective financial difficulties had higher risk of reporting 'less than
      good' health. In contrast in later life, subjective financial well-being was
      associated with health, but the effect of income on health was mediated entirely
      through subjective financial well-being. The poorer health of the
      divorced/separated was also entirely mediated by differences in subjective
      financial well-being. Research on health inequalities should pay greater
      attention to the link between subjective financial hardship and ill-health,
      especially during periods of greater economic difficulties and financial
      austerity. 

PMID- 24444835
TI  - Physicians' perceptions of autonomy across practice types: Is autonomy in solo
      practice a myth?
AB  - Physicians in the United States are now less likely to practice in smaller, more
      traditional, solo practices, and more likely to practice in larger group
      practices. Though older theory predicts conflict between bureaucracy and
      professional autonomy, studies have shown that professions in general, and
      physicians in particular, have adapted to organizational constraints. However,
      much work remains in clarifying the nature of this relationship and how exactly
      physicians have adapted to various organizational settings. To this end, the
      present study examines physicians' autonomy experiences in different decision
      types between organization sizes. Specifically, I ask: In what kinds of decisions
      do doctors perceive autonomous control? How does this vary by organizational
      size? Using stacked "spell" data constructed from the Community Tracking Study
      (CTS) Physician Survey (1996-2005) (n = 16,519) I examine how physicians'
      perceptions of autonomy vary between solo/two physician practices, small group
      practices with three to ten physicians, and large practices with ten or more
      physicians, in two kinds of decisions: logistic-based and knowledge-based
      decisions. Capitalizing on the longitudinal nature of the data I estimate how
      changes in practice size are associated with perceptions of autonomy, accounting
      for previous reports of autonomy. I also test whether managed care involvement,
      practice ownership, and salaried employment help explain part of this
      relationship. I find that while physicians practicing in larger group practices
      reported lower levels of autonomy in logistic-based decisions, physicians in
      solo/two physician practices reported lower levels of autonomy in knowledge-based
      decisions. Managed care involvement and ownership explain some, but not all, of
      the associations. These findings suggest that professional adaptation to various
      organizational settings can lead to varying levels of perceived autonomy across
      different kinds of decisions. 

PMID- 24444836
TI  - Child passenger safety laws in the United States, 1978-2010: policy diffusion in
      the absence of strong federal intervention.
AB  - This article examines the diffusion of U.S. state child passenger safety laws,
      analyzing over-time changes and inter-state differences in all identifiable
      features of laws that plausibly influence crash-related morbidity and mortality.
      The observed trend shows many states' continuing efforts to update their laws to
      be consistent with latest motor vehicle safety recommendations, with each state
      modifying their laws on average 6 times over the 30-year period. However, there
      has been a considerable time lag in knowledge diffusion and policy adoption. Even
      though empirical evidence supporting the protective effect of child restraint
      devices was available in the early 1970s, laws requiring their use were not
      adopted by all 50 states until 1986. For laws requiring minors to be seated in
      rear seats, the first state law adoption did not occur until two decades after
      the evidence became publicly available. As of 2010, only 12 states explicitly
      required the use of booster seats, 9 for infant seats and 6 for toddler seats.
      There is also great variation among states in defining the child population to be
      covered by the laws, the vehicle operators subject to compliance, and the
      penalties resulting from non-compliance. Some states cover only up to 4-year-olds
      while others cover children up to age 17. As of 2010, states have as many as 14
      exemptions, such as those for non-residents, non-parents, commercial vehicles,
      large vehicles, or vehicles without seatbelts. Factors such as the complexity of
      the state of the science, the changing nature of guidelines (from age to
      height/weight-related criteria), and the absence of coordinated federal actions
      are potential explanations for the observed patterns. The resulting uneven policy
      landscape among states suggests a strong need for improved communication among
      state legislators, public health researchers, advocates and concerned citizen
      groups to promote more efficient and effective policymaking. 

PMID- 24444838
TI  - Political contexts and maternal health policy: insights from a comparison of
      south Indian states.
AB  - Nearly 300,000 women die from pregnancy-related complications each year. One
      fifth of these deaths occur in India. Maternal survival rose on India's national
      policy agenda in the mid-2000s, but responsibility for health policy and
      implementation in the federal system is largely devolved to the state level where
      priority for the issue and maternal health outcomes vary. This study investigates
      sources of variation in maternal health policy and implementation sub-nationally
      in India. The study is guided by four analytical categories drawn from policy
      process literature: constitutional, governing and social structures; political
      contexts; actors and ideas. The experiences of two south Indian states-Tamil Nadu
      a leader and Karnataka a relatively slow mover-are examined. Process-tracing, a
      case study methodology that helps to identify roles of complex historical events
      in causal processes, was employed to investigate the research question in each
      state. The study is informed by interviews with public health policy experts and
      service delivery professionals, observation of implementation sites and archival
      document analysis. Historical legacies-Tamil Nadu's non-Brahmin social movement
      and Karnataka's developmental disparities combined with decentralization-shape
      the states' political contexts, affecting variation in maternal health policy and
      implementation. Competition to advance consistent political priorities across
      regimes in Tamil Nadu offers fertile ground for policy entrepreneurship and
      strong public health system administration facilitates progress. Inconsistent
      political priorities and relatively weak public health system administration
      frustrate progress in Karnataka. These variations offer insights to the ways in
      which sub-national political and administrative contexts shape health policy and
      implementation. 

PMID- 24444837
TI  - Labor migration, externalities and ethics: theorizing the meso-level determinants
      of HIV vulnerability.
AB  - This paper discusses labor migration as an example of how focusing on the meso
      level highlights the social processes through which structural factors produce
      HIV risk. Situating that argument in relation to existing work on economic
      organization and HIV risk as well as research on labor migration and HIV
      vulnerabilities, the paper demonstrates how analyzing the processes through which
      labor migration creates vulnerability can shift attention away from the proximate
      behavioral determinants of HIV risk and toward the community and policy levels.
      Further, it presents the concepts of externalities and the ethics of consumption,
      which underline how both producers and consumers benefit from low-waged migrant
      labor, and thus are responsible for the externalization of HIV risk
      characteristic of supply chains that rely on migrant labor. These concepts point
      to strategies through which researchers and advocates could press the public and
      private sectors to improve the conditions in which migrants live and work, with
      implications for HIV as well as other health outcomes. 

PMID- 24444839
TI  - A fundamental cause approach to the study of disparities in lung cancer and
      pancreatic cancer mortality in the United States.
AB  - This study examines how associations between socioeconomic status (SES) and lung
      and pancreatic cancer mortality have changed over time in the U.S. The
      fundamental cause hypothesis predicts as diseases become more preventable due to
      innovation in medical knowledge or technology, individuals with greater access to
      resources will disproportionately benefit, triggering the formation or worsening
      of health disparities along social cleavages. We examine socioeconomic
      disparities in mortality due to lung cancer, a disease that became increasingly
      preventable with the development and dissemination of knowledge of the causal
      link between smoking cigarettes and lung cancer, and compare it to that of
      pancreatic cancer, a disease for which there have been no major prevention or
      treatment innovations. County-level disease-specific mortality rates for those
      >=45 years, adjusted for sex, race, and age during 1968-2009 are derived from
      death certificate and population data from the National Center for Health
      Statistics. SES is measured using five county-level variables from four decennial
      censuses, interpolating values for intercensal years. Negative binomial
      regression was used to model mortality. Results suggest the impact of SES on lung
      cancer mortality increases 0.5% per year during this period. Although lung cancer
      mortality rates are initially higher in higher SES counties, by 1980 persons in
      lower SES counties are at greater risk and by 2009 the difference in mortality
      between counties with SES one SD above compared to one SD below average was 33
      people per 100,000. In contrast, we find a small but significant reverse SES
      gradient in pancreatic cancer mortality that does not change over time. These
      data support the fundamental cause hypothesis: social conditions influencing
      access to resources more greatly impact mortality when preventative knowledge
      exists. Public health interventions and policies should facilitate more equitable
      distribution of new health-enhancing knowledge and faster uptake and utilization
      among lower SES groups. 

PMID- 24444840
TI  - The risk of unintended pregnancy among young women with mental health symptoms.
AB  - Depression and stress have been linked with poor contraceptive behavior, but
      whether existing mental health symptoms influence women's subsequent risk of
      unintended pregnancy is unclear. We prospectively examined the effect of
      depression and stress symptoms on young women's pregnancy risk over one year. We
      used panel data from a longitudinal study of 992 U.S. women ages 18-20 years who
      reported a strong desire to avoid pregnancy. Weekly journal surveys measured
      relationship, contraceptive use and pregnancy outcomes. We examined 27,572
      journal surveys from 940 women over the first study year. Our outcome was self
      reported pregnancy. At baseline, we assessed moderate/severe depression (CESD-5)
      and stress (PSS-4) symptoms. We estimated the effect of baseline mental health
      symptoms on pregnancy risk with discrete-time, mixed-effects, proportional hazard
      models using logistic regression. At baseline, 24% and 23% of women reported
      moderate/severe depression and stress symptoms, respectively. Ten percent of
      young women not intending pregnancy became pregnant during the study. Rates of
      pregnancy were higher among women with baseline depression (14% versus 9%, p =
      0.04) and stress (15% versus 9%, p = 0.03) compared to women without symptoms. In
      multivariable models, the risk of pregnancy was 1.6 times higher among women with
      stress symptoms compared to those without stress (aRR 1.6, CI 1.1,2.7). Women
      with co-occurring stress and depression symptoms had over twice the risk of
      pregnancy (aRR 2.1, CI 1.1,3.8) compared to those without symptoms. Among women
      without a prior pregnancy, having co-occurring stress and depression symptoms was
      the strongest predictor of subsequent pregnancy (aRR 2.3, CI 1.2,4.3), while
      stress alone was the strongest predictor among women with a prior pregnancy (aRR
      3.0, CI 1.1,8.8). Depression symptoms were not independently associated with
      young women's pregnancy risk. In conclusion, stress, and especially co-occurring
      stress and depression symptoms, consistently and adversely influenced these young
      women's risk of unintended pregnancy over one year. 

PMID- 24444841
TI  - Health sector demand-side financial incentives in low- and middle-income
      countries: a systematic review on demand- and supply-side effects.
AB  - Demand-side financial incentive (DSF) is an emerging strategy to improve health
      seeking behavior and health status in many low- and middle-income countries. This
      narrative synthesis assessed the demand- and supply-side effects of DSF. Forty
      one electronic data bases were searched to screen relevant experimental and quasi
      experimental study designs. Out of the 64 selected papers, 28 were eligible for
      this review and they described 19 DSF initiatives across Asia, Africa and Latin
      America. There were three categories of initiatives, namely long-run multi
      sectoral programs or LMPs (governmental); long-run health-exclusive programs
      (governmental); and short-run health-exclusive initiatives (both governmental and
      non-governmental). Irrespective of the nature of incentives and initiatives, all
      DSF programs could achieve their expected behavioral outcomes on healthcare
      seeking and utilization substantially. However, there existed a few negative and
      perverse outcomes on health seeking behavior and DSF's impact on continuous
      health seeking choices (e.g. bed net use and routine adult health check-ups) was
      mixed. Their effects on maternal health status, diarrhea, malaria and out-of
      pocket expenditure were under-explored; while chronic non-communicable diseases
      were not directly covered by any DSF programs. DSF could reduce HIV prevalence
      and child deaths, and enhance nutritional and growth status of children. The
      direction and magnitude of their effects on health status was elastic to the
      evaluation design employed. On health system benefits, despite prioritizing on
      vulnerable groups, DSF's substantial effect on the poorest of the poor was mixed
      compared to that on the relatively richer groups. Though DSF initiatives intended
      to improve service delivery status, many could not optimally do so, especially to
      meet the additionally generated demand for care. Causal pathways of DSF's effects
      should be explored in-depth for mid-course corrections and cross-country learning
      on their design, implementation and evaluation. More policy-specific analyses on
      LMPs are needed to assess how 'multi-sectoral' approaches can be cost-effective
      and sustainable in the long run compared to 'health exclusive' incentives. 

PMID- 24444842
TI  - Household income and health problems during a period of labour-market change and
      widening income inequalities - a study among the Finnish population between 1987
      and 2007.
AB  - Income inequalities widened considerably from 1987 to 2007 in Finland. We
      compared the association between household income and health problems across
      three periods and in several different ways of modelling the dependence. Our aim
      was to find out whether the change in the distribution of income might have led
      to wider income-related inequalities in health problems. The data represent an 11
      per-cent random sample of the Finnish population, and we restricted the analysed
      sample to those between 18 and 67 years of age and not in receipt of any pension
      in each of the three six-year periods examined (n between 280,106 and 291,198).
      The health outcome was sickness-allowance days compensated. Household-equivalent
      taxable income was applied with two different scale transformations: firstly, as
      real income adjusted for price level and secondly, as rank position on the income
      distribution. We used negative binomial regression models, with and without zero
      inflation, as well as decomposition analysis. We found that sickness-allowance
      days decreased with increasing income, while differences in the shape and
      magnitude of the association were found between the scales and the periods.
      During the study period the association strengthened considerably at both the
      lowest fifth and the top fifth of the rank scale, while the observed per-unit
      effect of real income changed less. Decomposition analysis suggested that
      slightly less than half of the observed increase in concentration of health
      problems at lower end of the rank scale could be accounted for by the change in
      real income distribution. The results indicate that widening differences in
      household consumption potential may have contributed to an intensified impact of
      household income on inequalities in health problems. Explaining the change only
      in terms of consumption potential, however, was problematic, and changes in the
      interdependence of labour-market advantage and health problems are likely to
      contribute as well. 

PMID- 24444843
TI  - Exploring personal interests of physicians in hospitals and specialty clinics.
AB  - Physicians' interests substantially influence intra-organizational dynamics in
      hospitals, though little is known about the actual content and structure of these
      interests. The objective of this study was to both identify and build a
      structured model of physicians' interests. Based on literature and 27 semi
      structured interviews with physicians, a questionnaire containing 10 interests
      was developed. Next, 1475 physicians in the Netherlands filled out an online
      survey. Analyses of the data revealed a distinction between the primary interest
      of 'helping patients as well as possible' and nine secondary interests. Factor
      analysis identified the main secondary interest dimensions as work-related,
      setting-related, and life-related. Value attached to interests differs between
      specialties and types of hospitals. The influence of hospital type on the value
      attached to interests is stronger than the influence of specialty group on the
      value attached to interests. Insight in the relative importance of different
      interests may help policy-makers make decisions that foster shared interests. 

PMID- 24444844
TI  - Exploring the migration decisions of health workers and trainees from Africa: a
      meta-ethnographic synthesis.
AB  - The migration of healthcare workers from Africa depletes countries already
      suffering from substantial staffing shortages and considerable disease burdens.
      The recruitment of such individuals by high income countries has been condemned
      by the World Health Organisation. However, understanding the reasons why
      healthcare workers migrate is essential, in order to attempt to alter migration
      decisions. We aimed to systematically analyse factors influencing healthcare
      workers' decisions to migrate from Africa. We systematically searched CINAHL
      (1980-Nov 2010), Embase (1980-Nov 2010), Global Health (1973-Nov 2010) and
      Medline (1950-Nov 2010) for qualitative studies of healthcare workers from Africa
      which specifically explored views about migration. Two reviewers identified
      articles, extracted data and assessed quality of included studies. Meta
      ethnography was used to synthesise new lines of understanding and meaning from
      the data. The search identified 1203 articles from which we included six studies
      of healthcare workers trained in seven African countries, namely doctors or
      medical students (two studies), nurses (three), and pharmacy students (one
      study). Using meta-ethnographic synthesis we produced six lines of argument
      relating to the migration decisions of healthcare workers: 1) Struggle to realise
      unmet material expectations of self, family and society, 2) Strain and emotion,
      interpersonal discord, and insecurity in workplace, 3) Fear from threats to
      personal or family safety, in and out of workplace, 4) Absence of adequate
      professional support and development, 5) Desire for professional prestige and
      respect, 6) Conviction that hopes and goals for the future will be fulfilled
      overseas. We conclude that a complex interaction of factors contribute to the
      migration decisions of healthcare workers from Africa. Some of the factors
      identified are more amenable to change than others, and addressing these may
      significantly affect migration decisions of African healthcare workers in the
      future. 

PMID- 24444845
TI  - The effect of asset-based wealth inequality on problem drinking among rural Thai
      elders: a prospective population-based cohort study.
AB  - Evidence on the link between income inequality and alcohol-related problems is
      scarce, inconclusive and dominated by studies from the developed world. The use
      of income as a proxy measure for wealth is also questionable, particularly in
      developing countries. The goal of the present study is to explore the contextual
      influence of asset-based wealth inequality on problem drinking among Thai older
      adults. A population-based cohort study with a one-year follow-up was nested in a
      Demographic Surveillance System (DSS) of 100 villages in western Thailand. Data
      were drawn from a random sample of 1104 older residents, aged 60 or over (one per
      household) drawn from all 100 villages, of whom 982 (89%) provided problem
      drinking data at follow-up. The primary outcome measure was a validated Thai
      version of the Alcohol-Used Disorder Identification Test for problem drinking.
      Living in areas of high wealth inequality was prospectively associated with a
      greater risk for problem drinking among older people (adjusted odds ratio 2.30,
      95% confidence intervals 1.02-5.22), after adjusting for individual-level and
      village-level factors. A rise in wealth inequality over the year was also
      independently associated with an increased risk of problem drinking (adjusted
      odds ratio 2.89, 95% confidence intervals 1.24-6.65). The associations were not
      explained by the social capital, status anxiety or psychosocial stress variables.
      The data suggest that wealth inequality and an increase in inequality across time
      lead to a greater risk of problem drinking. Efforts should be directed towards
      reducing gaps and preventing large jumps in inequality in the communities.
      Further research should investigate the effect of asset-based inequality on
      various health risk behaviors and its specific mediating pathways. 

PMID- 24444846
TI  - The effect of unpaid caregiving intensity on labour force participation: results
      from a multinomial endogenous treatment model.
AB  - It is well acknowledged that the intensity of caregiving affects the labour force
      participation of caregivers. The literature so far has not, however, been able to
      control effectively for the endogeneity of caregiving intensity. This paper
      contributes by dealing with the endogeneity of unpaid caregiving intensity when
      examining its impact on the labour force participation of caregivers. We
      distinguish between care provided to people who cohabit with the care recipient
      and care provided to recipients who reside elsewhere, as well as between primary
      and secondary caring roles. We address the endogeneity of selection in various
      care intensity roles via an instrumental variables approach, using the health
      status of potential care recipients as instruments. Data from wave 8 of the
      Household Income and Labour Dynamics in Australia survey which was undertaken in
      2008 are used. We focus on a sample of 7845 working age males and females. Ruling
      out the endogeneity of any caregiving intensity role, we find that caregiving has
      a significant deterrent effect on caregivers' employment. This deterrent effect
      however is concentrated among those who identify as the main caregiver and the
      result appears to be the same irrespective of gender. Providing care as the main
      caregiver reduces the probability of employment by approximately 12 percentage
      points for both males and females, regardless of whether or not the caregivers
      cohabit with the care recipients. By contrast, we find no statistically
      significant impact of providing care as a secondary caregiver on the employment
      probabilities of either males or females. These results are germane to the
      development of policies that may affect informal caregiving and, thereby, the
      labour force decisions of carers. 

PMID- 24444847
TI  - Process evaluation of a problem solving intervention to prevent recurrent
      sickness absence in workers with common mental disorders.
AB  - Common mental disorders (CMDs) are a major cause of sickness absence. Twenty to
      30% of the workers who return to work after sickness absence due to CMDs
      experience recurrent sickness absence. We developed the Stimulating Healthy
      participation And Relapse Prevention (SHARP)-at work intervention, a problem
      solving intervention delivered by occupational physicians (OPs), to prevent
      recurrent sickness absence in this worker population in The Netherlands. A
      process evaluation was conducted alongside a cluster-randomised controlled trial
      to (1) evaluate whether the SHARP-at work intervention was implemented according
      to the protocol and differed from treatment in the control group, and (2) to
      investigate the relationship between the key elements of the intervention and the
      effect outcome (i.e. recurrent sickness absence). We collected process data for
      both the intervention and control group on recruitment, reach, dose delivered,
      dose received, fidelity, context and satisfaction. Data on recurrent sickness
      absence was collected through the registry system of the collaborating
      occupational health service. The study was performed in the Netherlands, and
      between 2010 and 2012, 154 OPs and 158 participants participated. Compared to the
      control group, participants in the intervention group more frequently had two or
      more consultations with the OP (odds ratio [OR] = 3.2, 95% confidence interval
      [CI] = 1.2-8.8) and completed more assignments (OR = 33.8, 95% CI = 10.4-109.5)
      as recommended in the intervention protocol. OPs and participants were satisfied
      with the intervention and rated it as applicable. Several individual intervention
      components were linked to the effect outcome. The process evaluation showed that
      the SHARP-at work intervention was conducted according to the protocol for the
      majority of the participants and well-received by OPs and participants.
      Furthermore, the intervention differed from treatment in the control group.
      Overall, the results provide support for implementing the intervention in
      practice. 

PMID- 24444848
TI  - Cannabis careers revisited: applying Howard S. Becker's theory to present-day
      cannabis use.
AB  - A considerable part of today's sociological research on recreational drug use is
      (explicitly or implicitly) inspired by Howard Becker's classical model of deviant
      careers. The aim of the present paper is to directly apply Becker's theory to
      empirical data on present-day cannabis use and to suggest a revision of the
      theory. As part of this, we propose a stretch of the sociological approach
      represented by Becker and followers in order to include, not only recreational
      drug use, but also use for which young people have sought treatment. The paper is
      based on 30 qualitative interviews with young people in treatment for cannabis
      problems in Copenhagen, Denmark. We suggest a revision of Becker's career model
      in relation to four aspects: initiation of cannabis use, differentiation between
      socially integrated and individualised, disintegrated use, social control from
      non-users, and the users' moral stance on cannabis. A central point of the paper
      is that social interaction may both motivate cannabis use, as Becker proposed,
      and serve as a protective factor against extensive, problematic use. 

PMID- 24444849
TI  - Cognitive social capital and mental illness during economic crisis: a nationwide
      population-based study in Greece.
AB  - The ongoing financial crisis in Greece has yielded adverse effects on the mental
      health of the population. In this context, the particular study investigates the
      link between two indices of cognitive social capital; namely interpersonal and
      institutional trust, and the presence of major depression and generalized anxiety
      disorder. A random and representative sample of 2256 respondents took part in a
      cross-sectional nationwide telephone survey the time period February-April 2011
      (Response Rate = 80.5%), after being recruited from the national phone number
      databank. Major depression and generalized anxiety disorder were assessed with
      the Structured Clinical Interview, while for interpersonal and institutional
      trust the pertinent questions of the European Social Survey were utilized. Socio
      demographic variables were also encompassed in the research instrument, while
      participants' degree of financial strain was assessed through the Index of
      Personal Economic Distress. Both interpersonal and institutional trust were found
      to constitute protective factors against the presence of major depression, but
      not against generalized anxiety disorder for people experiencing low economic
      hardship. Nonetheless, in people experiencing high financial strain,
      interpersonal and institutional trust were not found to bear any association with
      the presence of the two disorders. Consistent with these, the present study shows
      that the effect of social capital on mental health is not uniform, as evident by
      the different pattern of results for the two disorders. Furthermore, cognitive
      social capital no longer exerts its protective influence on mental health if
      individuals experience high economic distress. As a corollary of this,
      interventions aiming at mitigating the mental health effects of economic
      downturns cannot rely solely on the enhancement of social capital, but also on
      alleviating economic burden. 

PMID- 24444851
TI  - Medicalizing to demedicalize: lactation consultants and the (de)medicalization of
      breastfeeding.
AB  - This paper uses the domain of breastfeeding in the U.S. and the work of
      International Board Certified Lactation Consultants to refine the concept of
      medicalization-demedicalization. Given lactation consultants' origins and current
      role in maternity care, they provide a unique lens on these processes because
      they are positioned at the crossroads of medicalization and demedicalization.
      Using 150 h of ethnographic observation and 39 interviews conducted between 2008
      and 2012, I identify aspects of medicalization-demedicalization in the work of
      lactation consultants according to four dimensions: medical definition, medical
      control, pathology, and medical technology. Lactation consultants work to
      demedicalize breastfeeding by challenging the construction of breastfeeding
      pathology and limiting intervention. At the same time, they hold a position of
      medical control and medicalize breastfeeding by reinforcing a medical definition
      and using medical technology to treat breastfeeding problems. However, lactation
      consultants are not only working toward demedicalization and medicalization
      simultaneously, but are also medicalizing to demedicalize. Their position of
      medical control over breastfeeding provides them with a certain measure of
      authority that they can use in their efforts to depathologize breastfeeding and
      limit medical intervention. These findings build upon previous research that has
      identified cases of medicalization and demedicalization occurring simultaneously
      and draw attention to the need for an understanding of medicalization
      demedicalization as a continuous process. Furthermore, the concept of
      "medicalizing to demedicalize" provides a novel contribution to the literature. 

PMID- 24444850
TI  - Modernization is associated with intensive breastfeeding patterns in the Bolivian
      Amazon.
AB  - For many traditional, non-industrialized populations, intensive and prolonged
      breastfeeding buffers infant health against poverty, poor sanitation, and limited
      health care. Due to novel influences on local economies, values, and beliefs, the
      traditional and largely beneficial breastfeeding patterns of such populations may
      be changing to the detriment of infant health. To assess if and why such changes
      are occurring in a traditional breastfeeding population, we document
      breastfeeding patterns in the Bolivian Tsimane, a forager-horticulturalist
      population in the early stages of modernization. Three predictions are developed
      and tested to evaluate the general hypothesis that modernizing influences
      encourage less intensive breastfeeding in the Tsimane: 1) Tsimane mothers in
      regions of higher infant mortality will practice more intensive BF; 2) Tsimane
      mothers who are located closer to a local market town will practice more
      intensive BF; and 3) Older Tsimane mothers will practice more intensive BF.
      Predictions were tested using a series of maternal interviews (from 2003 to 2011,
      n = 215) and observations of mother-infant dyads (from 2002 to 2007, n = 133).
      Tsimane breastfeeding patterns were generally intensive: 72% of mothers reported
      initiating BF within a few hours of birth, mean (+/-SD) age of CF introduction
      was 4.1 +/- 2.0 months, and mean (+/-SD) weaning age was 19.2 +/- 7.3 months.
      There was, however, intra-population variation in several dimensions of
      breastfeeding (initiation, frequency, duration, and complementary feeding).
      Contrary to our predictions, breastfeeding was most intensive in the most
      modernized Tsimane villages, and maternal age was not a significant predictor of
      breastfeeding patterns. Regional differences accounted for variation in most
      dimensions of breastfeeding (initiation, frequency, and complementary feeding).
      Future research should therefore identify constraints on breastfeeding in the
      less modernized Tsimane regions, and examine the formation of maternal beliefs
      regarding infant feeding. 

PMID- 24444852
TI  - Primary and secondary care attendance, anticonvulsant and antidepressant use and
      psychiatric contact 5-10 years after diagnosis in 188 patients with psychogenic
      non-epileptic seizures.
AB  - BACKGROUND AND OBJECTIVES: There have been few studies of long-term outcome in
      psychogenic non-epileptic seizures (PNES), and none of long-term healthcare
      utilization. METHODS: We studied attendance with seizures, healthcare use and
      employment over a 6-month period from the family doctors of 260 consecutive
      patients with psychogenic non-epileptic seizures (PNES), 5-10 years after
      diagnosis. RESULTS: We obtained clinical data in 188/260 patients (72.3%), of
      whom 60 (31.9%) had attended primary or secondary care with seizures in the
      previous 6 months. Predictors of attendance with seizures included a diagnosis of
      epilepsy+PNES (OR 5.7, p=0.009), work status (OR 3.9, p=0.027) and social
      security payments (OR 6.3, p=0.003). Latency to diagnosis was not predictive.
      Emergency admission data were available in 187 patients, of whom 25 (13.4%) had
      emergency hospital attendances. Prescription data were available for 172
      patients, of whom 154 had 'PNES only'. Of these, 17 (11.0%) remained on
      antiepileptic medication (AED). 68/172 patients (39.5%) were prescribed
      antidepressant (AD) drugs. We had psychiatric contact data in 185 patients, of
      whom 49 (26.5%) had accessed psychiatric services in the last 6 months.
      CONCLUSIONS: Surprisingly few of our patients had presented with seizures during
      the study period. Early reductions in both AED use and healthcare use were
      sustained long term. Although psychiatric and employment outcomes were less
      encouraging, some aspects of PNES outcome may be better than previously thought.

PMID- 24444854
TI  - Which target is best for patients with Parkinson's disease? A meta-analysis of
      pallidal and subthalamic stimulation.
AB  - BACKGROUND: There is a growing body of evidence demonstrating that deep brain
      stimulation (DBS) of globus pallidus internus (GPi DBS) and subthalamic nucleus
      (STN DBS) are effective treatment for patients with Parkinson's disease (PD).
      However, it remains controversial whether the best stimulation target for a PD
      patient is GPi or STN. METHODS: A computer literature search of PubMed was
      carried out. We included randomised studies with direct comparison between
      targets. The outcome of unified PD rating scale (UPDRS) III was expressed as the
      standardised mean difference (SMD) between targets in baseline to endpoint
      change. Pooled risk ratio (RR) between targets was also used to assess adverse
      events. RESULTS: Four studies, comprising a total sample size of 502 PD patients
      (254 GPi DBS, 248 STN DBS), were included in this meta-analysis. The overall
      effect of GPi DBS on UPDRS III was not significantly different from STN DBS
      (SMD=0.19, 95% CI -0.2 to 0.58, p=0.34, four studies, n=448). This result was
      heterogeneous (p=0.03, I(2)=66%). In terms of adverse events, depression was
      significantly less frequent in patients with GPi DBS than STN DBS with
      homogeneous studies (pooled RR=0.53, 95% CI 0.31 to 0.90, p=0.02, three studies,
      n=479, I(2)=48%). CONCLUSIONS: The effect of GPi DBS was similar to STN DBS
      except for depression, however, only three studies described depression as
      adverse events. We need additional randomised trials with direct comparison
      between targets based on unified scoring of adverse events.

PMID- 24444853
TI  - Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders.
AB  - BACKGROUND: For patients with psychiatric illnesses remaining refractory to
      'standard' therapies, neurosurgical procedures may be considered. Guidelines for
      safe and ethical conduct of such procedures have previously and independently
      been proposed by various local and regional expert groups. METHODS: To expand on
      these earlier documents, representative members of continental and international
      psychiatric and neurosurgical societies, joined efforts to further elaborate and
      adopt a pragmatic worldwide set of guidelines. These are intended to address a
      broad range of neuropsychiatric disorders, brain targets and neurosurgical
      techniques, taking into account cultural and social heterogeneities of healthcare
      environments. FINDINGS: The proposed consensus document highlights that, while
      stereotactic ablative procedures such as cingulotomy and capsulotomy for
      depression and obsessive-compulsive disorder are considered 'established' in some
      countries, they still lack level I evidence. Further, it is noted that deep brain
      stimulation in any brain target hitherto tried, and for any psychiatric or
      behavioural disorder, still remains at an investigational stage. Researchers are
      encouraged to design randomised controlled trials, based on scientific and data
      driven rationales for disease and brain target selection. Experienced
      multidisciplinary teams are a mandatory requirement for the safe and ethical
      conduct of any psychiatric neurosurgery, ensuring documented refractoriness of
      patients, proper consent procedures that respect patient's capacity and autonomy,
      multifaceted preoperative as well as postoperative long-term follow-up
      evaluation, and reporting of effects and side effects for all patients.
      INTERPRETATION: This consensus document on ethical and scientific conduct of
      psychiatric surgery worldwide is designed to enhance patient safety.

PMID- 24444855
TI  - Malformation risks of antiepileptic drug monotherapies in pregnancy: updated
      results from the UK and Ireland Epilepsy and Pregnancy Registers.
AB  - OBJECTIVES: Antiepileptic drug (AED) exposure during pregnancy increases the risk
      of major congenital malformations (MCMs). The magnitude of this risk varies by
      AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy
      Register of the risk of MCMs after monotherapy exposure to valproate,
      carbamazepine and lamotrigine. METHODS: Fifteen-year prospective observational
      study from 1996 until 2012. The main outcome measure is the MCM rate. RESULTS:
      Informative outcomes were available for 5206 cases. 1290 women were exposed to
      valproate monotherapy, 1718 to carbamazepine monotherapy and 2198 to lamotrigine
      monotherapy. The MCM risk with valproate monotherapy exposure in utero was 6.7%
      (95% CI 5.5% to 8.3%) compared with 2.6% with carbamazepine (95% CI 1.9% to 3.5%)
      and 2.3% with lamotrigine (95% CI 1.8% to 3.1%). A significant dose effect was
      seen with valproate (p=0.0006) and carbamazepine (p=0.03) exposed pregnancies. A
      non-significant trend towards higher MCM rate with increasing dose was found with
      lamotrigine. MCM rate for high-dose lamotrigine (>400 mg daily) was lower than
      the MCM rate for pregnancies exposed to <600 mg daily of valproate, but this was
      not significant (3.4% vs 5.0%, p=0.31). CONCLUSIONS: In utero exposure to
      valproate carries a significantly higher MCM risk than lamotrigine (p=0.0001) and
      carbamazepine (p=0.0001) monotherapy. In contrast to prior findings, high-dose
      lamotrigine was associated with fewer MCMs than all doses of valproate. While
      lamotrigine has a favourable profile compared with valproate for adverse
      pregnancy outcomes, the requirements for seizure control should not be
      overlooked.

PMID- 24444856
TI  - Capillary electrophoresis-based assay of phosphofructokinase-1.
AB  - An assay was developed for phosphofructokinase-1 (PFK-1) using capillary
      electrophoresis (CE). In the glycolytic pathway, this enzyme catalyzes the rate
      limiting step from fructose-6-phosphate and magnesium-bound adenosine
      triphosphate (Mg-ATP) to fructose-1,6-bisphosphate and magnesium-bound adenosine
      diphosphate (Mg-ADP). This enzyme has recently become a research target because
      of the importance of glycolysis in cancer and obesity. The CE assay for PFK-1 is
      based on the separation and detection by ultraviolet (UV) absorbance at 260 nm of
      Mg-ATP and Mg-ADP. The separation was enhanced by the addition of Mg2+ to the
      separation buffer. Inhibition studies of PFK-1 by aurintricarboxylic acid and
      palmitoyl coenzyme A were also performed. An IC50 value was determined for
      aurintricarboxylic acid, and this value matched values in the literature obtained
      using coupled spectrophotometric assays. This assay for PFK-1 directly monitors
      the enzyme-catalyzed reaction, and the CE separation reduces the potential of
      spectral interference by inhibitors.

PMID- 24444857
TI  - Symptomatic rectocele: what are the indications for repair?
AB  - BACKGROUND: The surgical indications for symptomatic rectocele are undefined, and
      surgery has high recurrence rates. We implemented magnetic resonance imaging
      defecography (MRID) to determine if utilizing strict inclusion criteria for
      rectocele repair improves outcomes. METHODS: Patients with obstructive defecation
      syndrome (ODS) who underwent dynamic MRID were evaluated. Indications for
      surgical repair were defecation requiring manual assistance and the following
      MRID results: anterior defect >2 cm, incomplete evacuation, and the absence of
      perineal descent. Primary outcomes were the change in quality of life (QOL)
      scores and recurrence. RESULTS: From 2006 to 2013, 143 patients who presented
      with ODS underwent MRID. Seventeen patients met the criteria for repair.
      Recurrence was low (5.8%) with a median follow-up of 23 months, QOL scores
      improved from 57.3 to 76.5 (P = .041). CONCLUSIONS: A minority of patients (12%)
      with ODS met the above criteria for rectocele repair. Patients who underwent
      repair had a significant improvement in QOL and low recurrence rate.

PMID- 24444858
TI  - Peritoneal Surface Disease Severity Score as a predictor of resectability in the
      treatment of peritoneal surface malignancies.
AB  - BACKGROUND: We evaluated the clinical utility of the Peritoneal Surface Disease
      Severity Score (PSDSS) as a preoperative predictor of resectability in the
      treatment of peritoneal surface malignancies. METHODS: Forty-nine patients were
      selected for cytoreductive surgery (CRS) plus hyperthermic intraperitoneal
      chemotherapy (HIPEC) and were stratified according to the PSDSS retrospectively.
      RESULTS: Of 52 cytoreductive surgeries performed in 49 patients, HIPEC was
      performed in 33 cases (63%). We analyzed 31 cases of appendiceal and colorectal
      cancer patients who underwent CRS and HIPEC and 12 who underwent CRS only. 68% of
      the patients in whom CRS and HIPEC was performed were classified as PSDSS stage I
      or II. Contrastingly, all patients in whom CRS and HIPEC was unachievable were
      scored as PSDSS stage III or IV. CONCLUSIONS: The outcomes of this study suggest
      that the PSDSS can be used as a preoperative assessment tool to predict disease
      resectability in the treatment of peritoneal surface malignancies.

PMID- 24444859
TI  - Has medical diplomacy reached an inflection point?

PMID- 24444860
TI  - The use of a perimeatal-based penile skin flap to cover the repair of a
      tubularized incised plate urethroplasty: from experimental surgery to clinical
      practice.
AB  - OBJECTIVE: To prospectively evaluate the efficacy and safety of a perimeatal
      based penile skin flap for neourethral coverage after repair of distal
      hypospadias with tubularized incised plate urethroplasty (TIPU). METHODS: In 12
      New Zealand white rabbits a ventral urethral defect was created and
      reconstruction was accomplished with continuous suture. An epithelialized defect
      based flap was harvested from the penile skin to cover the repaired defect. The
      animals were euthanized on the 28th postoperative day and their penises were
      processed for microscopic examination. In 32 children with distal hypospadias a
      TIPU was performed. A penile skin flap was created immediately below the distal
      end of the neourethra and used to cover the urethroplasty. RESULTS: Histological
      examinations revealed complete restoration of continuity of the stratified
      squamous epithelium without evidence of inflammation or fistula formation with
      full consistency with the underlying papillary reticular and corium. There were
      no cases of fistula formation. One patient developed meatal stenosis. All
      patients had a satisfactory cosmetic appearance and excellent functional results.
      CONCLUSION: The formation of a perimeatal-based skin flap is a simple and safe
      method of providing additional cover for the constructed neourethra after TIPU,
      minimizing the fistula rate.

PMID- 24444861
TI  - Commentary to 'caregivers of children with a disorder of sex development:
      associations between parenting and psychological distress'.

PMID- 24444863
TI  - Associations between properties linked with persistence in a collection of
      Staphylococcus aureus isolates from bovine mastitis.
AB  - Staphylococcus aureus is recognized worldwide as a pathogen causing many serious
      diseases in humans and animals, and is one of the most important etiological
      agents of clinical and subclinical bovine mastitis. The aim of the present study
      was to investigate and correlate properties, that may be associated with
      persistent mastitis, of S. aureus strains isolated from milk of cows suffering
      from mastitis: (i) expression of capsular antigens (CP5 or CP8) by specific
      ELISA; (ii) intracellular survival by invasion of MAC-T cells; and (iii) biofilm
      production by spectrophotometry analysis after growth in TSBglc. The results
      showed that (i) the proportion of strains expressing capsular antigen was higher
      in cap8- than in cap5-positive isolates; (ii) a correlation was observed between
      the capsular profile and the intracellular survival as well as the biofilm
      production; and (iii) the capsular profile, biofilm production and intracellular
      survival were associated with only two agr-groups. Statistical and clustering
      analysis allowed us to establish different profiles that could be associated with
      in vivo persistence. Indeed, isolates belonging to agr group II, expressing the
      capsular antigen CP8 and showing low intracellular survival are probably better
      adapted to an extracellular niche. Conversely, isolates belonging to agr group I
      that do not express any capsular antigen (CP5 or CP8) but show high intracellular
      survival are probably better adapted to an intracellular niche.

PMID- 24444862
TI  - Neuroplasticity-based auditory training via laptop computer improves cognition in
      young individuals with recent onset schizophrenia.
AB  - OBJECTIVE: Cognitive deficits that characterize schizophrenia are present in the
      prodrome, worsen with illness onset, and predict functional outcome. Cognitive
      dysfunction is thus a critical target for early intervention in young individuals
      with recent onset schizophrenia. METHOD: This 2-site double-blind randomized
      controlled trial investigated cognitive training of auditory processing/verbal
      learning in 86 subjects with recent onset schizophrenia (mean age of 21 years).
      Subjects were given laptop computers to take home and were asked to perform 40
      hours of training or 40 hours of commercial computer games over 8 weeks. We
      examined cognitive measures recommended by the Measurement and Treatment Research
      to Improve Cognition in Schizophrenia initiative (MATRICS), symptoms, and
      functioning. We also assessed baseline reward anticipation to index motivational
      system functioning and measured changes in auditory processing speed after 20
      hours of training to assess target engagement. RESULTS: Auditory training
      subjects demonstrated significant improvements in global cognition, verbal
      memory, and problem solving compared with those of computer games control
      subjects. Both groups showed a slight but significant decrease in symptoms and no
      change in functional outcome measures. Training-induced cognitive gains at
      posttraining showed significant associations with reward anticipation at baseline
      and with improvement in auditory processing speed at 20 hours. CONCLUSION:
      Neuroscience-informed cognitive training via laptop computer represents a
      promising treatment approach for cognitive dysfunction in early schizophrenia. An
      individual's baseline motivational system functioning (reward anticipation), and
      ability to engage in auditory processing speed improvement, may represent
      important predictors of treatment outcome. Future studies must investigate
      whether cognitive training improves functioning and how best to integrate it into
      critical psychosocial interventions.

PMID- 24444865
TI  - [Colorectal cancer screening: reaffirming the past and resolutely advancing
      toward the future].

PMID- 24444864
TI  - Neutralizing antibodies against influenza A in pigs before and after the 2009
      pandemic, Luxembourg.
AB  - Neutralizing antibodies against different swine influenza A viruses and pandemic
      H1N1 were analyzed in pigs before and after the pandemic. While in 2009
      neutralization of the pandemic virus could be explained by cross-reaction with
      swine influenza viruses this was not the case in at least 2 farms in 2012. 

PMID- 24444866
TI  - The value of the 12-lead ECG for evaluation and optimization of cardiac
      resynchronization therapy in daily clinical practice.
AB  - Based on existing literature and some new data we propose a simple three-step
      strategy using the standard 12-lead ECG for patient selection and optimal
      delivery of cardiac resynchronization therapy (CRT). (1) Complete LBBB with
      regard to the indication for CRT can probably best be identified by a QRS
      duration of >= 130 ms for women and >= 120 ms for men with the presence of mid
      QRS notch-/slurring in >= 2 contiguous leads of V1, V2, V5, V6, I and aVL. (2)
      Left ventricular (LV) free wall pacing should result in a positive QRS complex in
      lead V1, with estimation of the exact LV lead position in the circumferential and
      apico-basal direction using lead aVF and the precordial leads, respectively. Wide
      and fractionated LV-paced QRS complexes may indicate pacing in scar tissue. (3)
      Atrioventricular and interventricular stimulation intervals may be optimized by
      adjusting them until precordial leads show fusion patterns between left and right
      ventricular activation wavefronts in the QRS complex.

PMID- 24444867
TI  - QT/RR hysteresis.

PMID- 24444868
TI  - Predictors of outcome in adults with BCR-ABL negative acute lymphoblastic
      leukemia treated with a pediatric-based regimen.
AB  - We retrospectively evaluated the outcome of 156 adults age 17-60 with BCR-ABL
      negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol.
      The CR rate was 93%; 5-year overall survival (OS) and disease-free survival were
      66% and 70%, respectively. Age <34 years and low presenting WBC were independent
      predictors of favorable OS (p<0.0001). The 5 year OS of patients age <34 and 34
      60 presenting with a low WBC were 85% and 57%, respectively; the 5 year OS for
      those presenting with a high WBC were 57% and 30%, respectively. Cytogenetics and
      phenotype were not independent predictors of OS. 

PMID- 24444869
TI  - Balancing efficacy and safety of JAK inhibitors in myelofibrosis.

PMID- 24444870
TI  - Large-scale identification and comparative analysis of miRNA expression profile
      in the respiratory tree of the sea cucumber Apostichopus japonicus during
      aestivation.
AB  - The sea cucumber Apostichopus japonicus withstands high water temperatures in the
      summer by suppressing its metabolic rate and entering a state of aestivation. We
      hypothesized that changes in the expression of miRNAs could provide important
      post-transcriptional regulation of gene expression during hypometabolism via
      control over mRNA translation. The present study analyzed profiles of miRNA
      expression in the sea cucumber respiratory tree using Solexa deep sequencing
      technology. We identified 279 sea cucumber miRNAs, including 15 novel miRNAs
      specific to sea cucumber. Animals sampled during deep aestivation (DA; after at
      least 15 days of continuous torpor) were compared with animals from a non
      aestivation (NA) state (animals that had passed through aestivation and returned
      to an active state). We identified 30 differentially expressed miRNAs ([RPM
      (reads per million) >10, |FC| (|fold change|)>=1, FDR (false discovery
      rate)<0.01]) during aestivation, which were validated by two other miRNA
      profiling methods: miRNA microarray and real-time PCR. Among the most prominent
      miRNA species, miR-124, miR-124-3p, miR-79, miR-9 and miR-2010 were significantly
      over-expressed during deep aestivation compared with non-aestivation animals,
      suggesting that these miRNAs may play important roles in metabolic rate
      suppression during aestivation. High-throughput sequencing data and microarray
      data have been submitted to the GEO database with accession number: 16902695.

PMID- 24444871
TI  - Molecularly imprinted polymer for the selective extraction of cocaine and its
      metabolites, benzoylecgonine and ecgonine methyl ester, from biological fluids
      before LC-MS analysis.
AB  - Considering the important complexity of biological samples, a molecularly
      imprinted polymer (MIP) was applied to the selective extraction of cocaine and
      its two main metabolites, benzoylecgonine and ecgonine methyl ester from
      biological samples. The MIP was imprinted with cocaine and it was synthesized in
      acetonitrile with methacrylic acid as a functional monomer and ethylene glycol
      dimethacrylate as a crosslinker. The selectivity of the MIP was first assessed
      for the three target analytes in acetonitrile with recoveries higher than 80% on
      the MIP and lower than 30% on the non-imprinted polymer (NIP). The MIP was then
      evaluated for the selective extraction of these targets from real aqueous media,
      i.e. serum and urine samples. The pH adjustment of the sample as well as the
      optimization of the washing step led to a very selective extraction of cocaine
      from these media. A LOQ of 0.5ng/mL was obtained for cocaine in urine. Concerning
      cocaine metabolites, benzoylecgonine and ecgonine methyl ester, they were first
      extracted from urine by liquid-liquid extraction and the resulting extract was
      purified on the MIP. The results obtained with the MIP as compared to the LLE
      alone showed the great potential of the MIP extraction for the clean-up of the
      biological matrix. This procedure was tested for the extraction of the analytes
      from urine samples, leading to a very selective protocol with LOQs of 0.09ng/mL,
      0.4ng/mL and 1.1ng/mL for cocaine, benzolecgonine and ecgonine methyl ester
      respectively in urine samples. 

PMID- 24444872
TI  - Risk-adjusted prolonged length of stay as an alternative outcome measure for
      pediatric congenital cardiac surgery.
AB  - BACKGROUND: Morbid events after pediatric congenital cardiac surgery are
      increasingly used for better outcome measurement and quality comparisons. This
      study was undertaken to evaluate the relationship between a hospital's risk
      adjusted prevalence of prolonged postoperative length of stay (PLOS) and its risk
      adjusted mortality rate to investigate whether PLOS can serve as an appropriate
      quality measure for pediatric congenital cardiac surgery. METHODS: Risk-adjusted
      prevalence of prolonged PLOS for 12 programs in New York State was estimated
      using data from 4,776 operations in the New York State pediatric Cardiac Surgery
      Reporting System (2006-2009). We used logistic regression analysis to adjust for
      case mix and patient risk factors. The hospital-level correlation between risk
      adjusted prolonged PLOS and risk-adjusted mortality rates was examined using
      Spearman correlation coefficient analysis. RESULTS: Risk-adjusted prevalence of
      prolonged PLOS ranged from 7.48% to 36.52% for pediatric cardiac programs in New
      York State during the study period. The Spearman correlation test showed a strong
      positive relationship between a hospital's risk-adjusted prolonged PLOS and
      mortality rate (r = 0.83; p = 0.0008). CONCLUSIONS: Prolonged PLOS can be used in
      lieu of risk-adjusted mortality rates when it is not practical to use mortality
      rates owing to low case volume or decreasing mortality rates of some procedures.

PMID- 24444873
TI  - The effects of transcatheter valve crimping on pericardial leaflets.
AB  - BACKGROUND: Transcatheter aortic valve replacement has emerged as a promising
      therapy for treatment of severe aortic stenosis. Although it has been shown that
      these valves can be safely delivered and implanted, studies of valve longevity
      are lacking because of the infancy of the technology. Particularly, the effects
      of stent crimping on the valve's leaflets have not yet been sufficiently
      investigated. In this study, we have characterized the effects of crimping on
      pericardial leaflets in time and through the depth of the tissue. METHODS: To
      test the structural changes at the surface and deep layers of bovine pericardial
      leaflets, scanning electron microscopy and second-harmonic generation microscopy
      were used. An uncrimped tissue sample was imaged, followed by imaging a segment
      of tissue after crimping in a stented transcatheter valve, immediately after, at
      20 minutes, and 60 minutes after crimping. The crimping experiment was performed
      for multiple crimping sizes (ie, 14F, 16F, and 18F). We defined a damage index
      that quantifies the level of leaflet structural changes as a result of crimping.
      RESULTS: Based on the calculated damage indices and analyses of the raw images,
      it was determined that crimping does measurable damage to the leaflet tissue that
      persists with time. CONCLUSIONS: Significant tissue damage was observed at the
      surface layers of the leaflets. In the deeper tissue layers, damage was
      substantial for 14F crimping; however, it became less significant but still
      visible for larger collapse profiles. Crimping may induce substantial structural
      damage to pericardial leaflets that does not improve with time.

PMID- 24444874
TI  - Endoscopic endoluminal vacuum therapy in esophageal perforation.
AB  - BACKGROUND: Esophageal perforation is a serious disease with a high morbidity and
      mortality rate. Endoscopic vacuum therapy (EVT) is a new endoscopic treatment
      option, which is used to treat anastomotic leakages after rectal and esophageal
      resections. We report on 10 patients treated with EVT for esophageal perforation.
      METHODS: Clinical and therapy-related data such as age, sex, duration of
      intensive care stay, length of hospital stay, reasons for perforation, EVT
      associated complications, mortality, need for alternative treatment options, and
      course of infectious variables were analyzed. RESULTS: Ten patients were treated
      with 54 vacuum sponges that were placed in upper gastrointestinal defects. Causes
      for perforation were iatrogenic, spontaneous, or foreign body-associated. Mean
      number of sponge insertions was 5.4 (range, 2 to 12) with a mean period of 19 +/-
      14.26 days. Successful therapy was achieved in 9 of 10 patients. After successful
      primary treatment, 1 patient died during therapy as a result of general failure
      of the cardiovascular system. In 1 patient, surgical resection was necessary
      after repeated Mallory-Weiss lesions and minor perforations during the course of
      immunosuppressive therapy. In a third patient an endoscopic stent was inserted in
      the clean wound cavity after primary EVT. CONCLUSIONS: In this small trial EVT
      has been shown to be a safe and feasible therapy option for perforations of the
      upper gastrointestinal tract. If necessary, EVT can be combined with operative
      revision for better control of the local septic focus or used as a bridging
      procedure for wound conditioning before aggressive surgical treatment.

PMID- 24444875
TI  - Modified elephant trunk technique in distal anastomosis with the aid of antegrade
      selective cerebral perfusion for total arch replacement.
AB  - BACKGROUND: Secure distal anastomosis and reliable brain protection are
      indispensable for successful total arch replacement (TAR). In 2002, we introduced
      a modified elephant trunk technique, a novel approach to distal anastomosis, and
      employed antegrade selective cerebral perfusion. We retrospectively analyzed 107
      consecutive patients to evaluate the efficacy of this technique for TAR with
      antegrade selective cerebral perfusion. METHODS: Since 2002 we have employed
      moderate hypothermic circulatory arrest, selective antegrade cerebral perfusion,
      and open distal anastomosis with a modified elephant trunk technique in TAR.
      Between February 2002 and September 2011, 107 TARs were performed in 88 males and
      19 females (age, 33 to 88 years; mean, 70.9+/-9.5 years). Etiologies of cases
      were as follows: 89 true aneurysm due to atherosclerosis; 5 infectious aneurysm;
      1 aortic dilation with bicuspid aortic valve; 12 aortic dissection, including 1
      of acute aortic dissection case; and 2 Marfan syndrome. Concomitant procedures
      included 19 coronary artery bypass grafting (CABG) cases, 2 aortic valve
      replacement cases, 1 mitral valve plasty case, 1 Bentall procedure case, and 1
      case of Bentall with CABG. RESULTS: The operative mortality within 30 days was
      0.9% (1 of 107), and overall hospital mortality was 1.9% (2 of 107). Temporary
      and permanent neurologic dysfunction occurred in 5 patients each (4.7%). The
      Kaplan-Meier survival analysis revealed a 5-year survival rate of 91.8%.
      CONCLUSIONS: The modified elephant trunk technique using selective antegrade
      cerebral perfusion provided secure distal anastomosis and demonstrated excellent
      results, with low operative mortality and few neurologic complications.

PMID- 24444876
TI  - Fontan pathway growth: a quantitative evaluation of lateral tunnel and
      extracardiac cavopulmonary connections using serial cardiac magnetic resonance.
AB  - BACKGROUND: Typically, a Fontan connection is constructed as either a lateral
      tunnel (LT) pathway or an extracardiac (EC) conduit. The LT is formed partially
      by atrial wall and is assumed to have growth potential, but the extent and nature
      of LT pathway growth have not been well characterized. A quantitative analysis
      was performed to evaluate this issue. METHODS: Retrospective serial cardiac
      magnetic resonance data were obtained for 16 LT and 9 EC patients at 2 time
      points (mean time between studies, 4.2 +/- 1.6 years). Patient-specific anatomies
      and flows were reconstructed. Geometric parameters of Fontan pathway vessels and
      the descending aorta were quantified, normalized to body surface area (BSA), and
      compared between time points and Fontan pathway types. RESULTS: Absolute LT
      pathway mean diameters increased over time for all but 2 patients; EC pathway
      size did not change (2.4 +/- 2.2 mm vs 0.02 +/- 2.1 mm, p < 0.05). Normalized LT
      and EC diameters decreased, while the size of the descending aorta increased
      proportionally to BSA. Growth of other cavopulmonary vessels varied. The patterns
      and extent of LT pathway growth were heterogeneous. Absolute flows for all
      vessels analyzed, except for the superior vena cava, proportionally to BSA.
      CONCLUSIONS: Fontan pathway vessel diameter changes over time were not
      proportional to somatic growth but increases in pathway flows were; LT pathway
      diameter changes were highly variable. These factors may impact Fontan pathway
      resistance and hemodynamic efficiency. These findings provide further
      understanding of the different characteristics of LT and EC Fontan connections
      and set the stage for further investigation.

PMID- 24444877
TI  - Polyphenol compounds belonging to flavonoids inhibit activity of coagulation
      factor X.
AB  - Blood coagulation consists of series of zymogens which can be converted by
      limited proteolysis to active enzymes leading to the generation of thrombin and
      conversion of fibrinogen into fibrin by this enzyme. The activated factor X (FXa)
      forms prothrombinase complex on phosphatidylserine containing surface which is
      responsible for conversion of prothrombin to thrombin. One molecule of FXa
      generates more than 1000 thrombin molecules. Therefore FXa is a novel target for
      modern anticoagulant therapy. The aim of our present study is to examine the
      effects of the well-known plant polyphenolic compounds on factor Xa amidolytic
      activity and characterization of these interactions using bioinformatic ligand
      docking method. We observed that only four polyphenols belonging to flavonoids
      group: procyanidin B2, cyanidin, quercetin and silybin, had inhibitory effect on
      FXa activity. Bioinformatic analyses revealed that procyanidin B2, cyanidin,
      quercetin and silybin bound in the S1-S4 pockets located in vicinity of the FXa
      active site and blocked access of substrates to Ser195. The results presented
      here showed that flavonoids might be potential structural bases for design of new
      nature-based, safe, orally bioavailable direct FXa inhibitors. 

PMID- 24444878
TI  - Adsorption of microbial esterases on Bacillus subtilis-templated cobalt oxide
      nanoparticles.
AB  - Due to low diffusion rates and large surface areas, nanomaterials have received
      great interest as supporting materials for enzyme immobilization. Here, the
      preparation of a cobalt oxide nanoparticle using Bacillus subtilis as a
      biological template and use of the nanostructure for microbial esterase
      immobilization is described. Morphological features and size distributions were
      investigated using electron microscopy (EM) and dynamic light scattering (DLS).
      Catalytic properties of enzyme-coated nanostructures were investigated using 4
      methylumbelliferyl acetate and p-nitrophenyl (PNP) acetate as model substrates.
      Enzyme-coated nanostructures were observed to retain ~85% of the initial activity
      after 15 successive reaction cycles, and enzyme immobilization processes could be
      repeated four times without a loss of immobilization potential. The present work
      demonstrates that B. subtilis-templated cobalt oxide nanoparticles have the
      potential to be used as biocompatible immobilization materials, and are promising
      candidates for the preparation of effective nanobiocatalysts. 

PMID- 24444879
TI  - Characterization of surface layer proteins and its role in probiotic properties
      of three Lactobacillus strains.
AB  - The objective of this study was the characterization of the surface layer
      proteins (SLPs) and their functional role in the probiotic activity of
      Lactobacillus helveticus fb213, L. acidophilus fb116 and L. acidophilus fb214.
      SLPs were extracted and identified by SDS-PAGE, circular dichroism spectra and LC
      MS analysis. The results revealed that the molecular masses of the three proteins
      were 49.7 kDa, 46.0 kDa and 44.6 kDa, respectively. The secondary structures and
      amino acid compositions of the three proteins were found to be similar. After
      removing SLPs, the survival of the three lactobacilli in simulated gastric and
      intestinal juices was reduced by 2-3log as compared with survival of the intact
      cells. And the adhesion ability of the three strains to HT-29 cells decreased by
      61%, 65% and 92%, respectively. SLPs also inhibited the adhesion and invasion of
      Escherichia coli ATCC 43893 to HT-29 cells. These results suggest that SLPs are
      advantageous barriers for lactobacilli in the gastrointestinal tract, and these
      proteins help make it possible for lactobacilli to serve their probiotic
      functions.

PMID- 24444880
TI  - Evaluation of crocin and curcumin affinity on mushroom tyrosinase using surface
      plasmon resonance.
AB  - Tyrosinase inhibitors have potential applications in the cosmetics and food
      industries for preventing browning reactions and also as therapeutic drugs for
      neurodegenerative diseases such as Parkinson's. In this article, crocin and
      curcumin were evaluated as mushroom tyrosinase inhibitors. Results showed that,
      both compounds strongly inhibited the diphenolase activity than monophenolase.
      The IC50 values for diphenolase activity were estimated to be 0.11 mM and 0.18 mM
      for crocin and curcumin respectively. The binding kinetics of crocin and curcumin
      was studied with mushroom tyrosinase using surface plasmon resonance (SPR).
      Tyrosinase was immobilized on the gold surface of a Biacore sensor chip through
      amine coupling. Binding of inhibitors was analyzed by SPR without the need to
      further modify the surface or the use of other reagents. The binding constant KD
      (M) for mushroom tyrosinase obtained was 1.21*10(-4) M for crocin and 1.64*10(-4)
      M for curcumin, while showing a higher affinity for L-DOPA 1.95*10(-8) M, a
      substrate for tyrosinase (positive control). The study reveals the SPR sensor's
      ability to detect binding of the inhibitors.

PMID- 24444881
TI  - New Bacillus thuringiensis toxin combinations for biological control of
      lepidopteran larvae.
AB  - Cyt1Aa from Bacillus thuringiensis israelensis is known by its synergistical
      activity with B. thuringiensis and Bacillus sphaericus toxins. It is able to
      improve dipteran specific toxins activity and can prevent or overcome larval
      resistance to those proteins. The objective of the current study was to
      investigate the possible improvement of larvicidal activity of B. thuringiensis
      kurstaki expressing heterogeneous proteins Cyt1A and P20. cyt1A98 and p20 genes
      encoding the cytolytic protein (Cyt1A98) and the accessory protein (P20),
      respectively, were introduced individually and in combination into B.
      thuringiensis kurstaki strain BNS3. Immunoblot analysis evidenced the expression
      of these genes in the recombinant strains and hinted that P20 acts as molecular
      chaperone protecting Cyt1A98 from proteolytic attack in BNS3. The toxicities of
      recombinant strains were studied and revealed that BNS3pHTp20 exhibited higher
      activity than that of the negative control (BNS3pHTBlue) toward Ephestia
      kuehniella, but not toward Spodoptera littoralis. When expressed in combination
      with P20, Cyt1A98 enhanced BNS3 activity against E. kuehniella and S. littoralis.
      Thus, Cyt1Aa protein could enhance lepidopteran Cry insecticidal activity and
      would prevent larval resistance to the most commercialized B. thuringiensis
      kurstaki toxins. 

PMID- 24444882
TI  - Polymorphism of hen egg white lysozyme amyloid fibrils influences the
      cytotoxicity in LLC-PK1 epithelial kidney cells.
AB  - The polymorphism of amyloid fibrils is potentially crucial as it may underlie the
      natural variability of amyloid diseases and could be important in developing a
      fuller understanding of the molecular basis of protein deposition disorders. This
      study examines morphological differences in lysozyme fibrils and the implications
      of these differences in terms of cytotoxicity. The structural characteristics of
      amyloid fibrils formed under two different experimental conditions (acidic and
      neutral) were evaluated using spectroscopic methods, atomic force microscopy and
      image analysis. Growth curves and apoptotic/necrotic assays were used to
      determine the cytotoxic effect of fibrils on the LLC-PK1 renal cells. The results
      reveal that both types of mature lysozyme amyloid fibrils are actively involved
      in the cytotoxic process, however each exhibit different levels of cytotoxicity.
      Fibrils formed at acidic pH affect cell growth in a dose-dependent manner, but a
      threshold-dependent inhibition of cell growth was observed in the case of
      lysozyme fibrils prepared at neutral pH. Experiments examining the mechanism of
      the cell death suggest that both types of mature lysozyme fibrils trigger late
      apoptosis/necrosis at different fibril concentrations. Our findings clearly
      indicate that the intrinsic differences between amyloid fibrils due to their
      polymorphism result in different degrees of cytotoxicity. 

PMID- 24444883
TI  - Free radical mediated grafting of chitosan with caffeic and ferulic acids:
      structures and antioxidant activity.
AB  - In this study, two water soluble chitosan derivatives were synthesized by
      grafting caffeic acid (CA) and ferulic acid (FA) onto chitosan via a free radical
      mediated method. The structural characterization, antioxidant activity in vitro
      and in vivo of chitosan derivatives were determined. Results showed that the UV
      vis absorption peaks of chitosan derivatives shifted toward longer wavelengths.
      FT-IR spectroscopy exhibited the typical phenolic characteristics within 1450
      1600 cm(-1). (1)H NMR spectroscopy showed new peaks of phenyl protons at 6.2-7.6
      ppm. (13)C NMR spectroscopy showed additional peaks between 110 and 150 ppm
      assigned to the C=C of phenolic groups. These results all confirmed the
      successful grafting of CA and FA onto chitosan backbones. The chitosan
      derivatives had decreased thermal stability and crystallinity as compared to
      chitosan. In vitro assays showed that the antioxidant activity decreased in the
      order of CA-g-chitosan>FA-g-chitosan>chitosan. Moreover, administration of the
      chitosan derivatives could significantly increase antioxidant enzymes activities
      and decrease malondialdehyde levels in both serums and livers of d-galactose
      induced aging mice. Our results indicated the potential of CA-g-chitosan and FA-g
      chitosan in the development of novel antioxidant agents.

PMID- 24444885
TI  - Purification of chitinase/chitosanase from Bacillus cereus and discovery of an
      enzyme inhibitor.
AB  - A chitinase and a chitosanase were induced from a squid pen powder (SPP)
      containing medium of Bacillus cereus TKU030 and purified by precipitation with
      ammonium sulphate and combined column chromatography. The purified chitinase and
      chitosanase exhibited optimum activity at 60  degrees C, pH 5-6 and 40  degrees
      C, pH 4, respectively. The chitinase and chitosanase were stable at 25-60 
      degrees C, pH 4-7 and 25-50  degrees C, pH 3-7, respectively. The chitinase and
      chitosanase showed the highest activity toward beta-chitin and 60% DD chitosan,
      respectively. The chitinase was significantly inhibited by Mn(2+) and EDTA but
      activated by Cu(2+), Fe(2+) and Ca(2+). The chitosanase was significantly
      inhibited by Cu(2+), Fe(2+), Zn(2+), Mn(2+) and EDTA. The chitinase showed high
      stability in the presence of various surfactants, such as SDS, Tween 20, Tween 40
      and Triton X-100. In contrast, these surfactants were inhibitors of the
      chitosanase. The chitinase and chitosanase were also inhibited by TKUPSP017, a
      small synthetic boron-containing molecule with a BF3K side-chain. However,
      TKUPSP017 enhanced the growth of B. cereus TKU030 in SPP-containing medium.

PMID- 24444884
TI  - Associations between resumption of postpartum ovarian activity, uterine health
      and concentrations of metabolites and acute phase proteins during the transition
      period in Holstein cows.
AB  - The resumption of ovarian activity, uterine health, severity of the negative
      energy balance and the synthesis of inflammatory mediators during the transition
      period in dairy cows are interrelated. Therefore, the aim of this study was to
      evaluate the association between the resumption of postpartum ovarian activity
      and the percentage of polymorphonuclear (PMN) cells in endometrial cytology,
      lipid mobilization and the secretion of acute phase proteins. For this study, 20
      multiparous Holstein cows were used. Blood samples that were collected from 21d
      before calving to 44d in milk (DIM) were analyzed for serum glucose, non
      esterified fatty acids (NEFA), insulin, haptoglobin, albumin, paraoxonase and
      progesterone. Endometrial cytology was performed at 37+/-2DIM to evaluate the
      percentage of PMN cells in the uterine flushing. Cows were divided into two
      groups: (1) ovulatory cows (n=12), which returned to ovarian activity by 44+/
      2DIM; and (2) anovulatory cows (n=8), which did not resume ovarian activity
      during this period. Ovulatory cows had a lower (P=0.05) percentage of PMN cells
      in endometrial cytology than anovulatory cows (26.3+/-8.3% vs. 53.4+/-16.9%,
      respectively). Ovulatory cows had higher serum albumin during the pre- (P=0.03)
      and postpartum periods (P=0.01), and tended to have lower haptoglobin
      concentrations in the prepartum period (P=0.07) and higher paraoxonase activity
      in the postpartum period (P=0.09). In conclusion, cows that resumed ovarian
      activity early in the postpartum period had higher albumin concentrations in the
      peripartum period, which were associated with a lower percentage of uterine PMN
      cells. 

PMID- 24444886
TI  - Chondroitin sulfate-capped gold nanoparticles for the oral delivery of insulin.
AB  - Chondroitin sulfate (CS)-capped gold nanoparticles (AuNPs) were synthesized and
      its feasibility for oral insulin (INS) delivery was investigated in vivo. CS was
      used as both reducing and stabilizing agent in the synthesis of AuNPs with around
      48 nm mean diameter, narrow size distribution, and negative zeta potential. After
      loading INS into CS-capped AuNPs structure, NPs with about 123 nm mean diameter,
      narrow size distribution, and negative zeta potential were successfully
      fabricated. By surface plasmon resonance (SPR) measurement, 0.5% (w/v) CS was
      chosen for the synthesis of AuNPs. Stability of AuNPs and AuNPs/INS was
      maintained for 7 weeks according to SPR study. Cytotoxicity of AuNPs/INS in Caco
      2 cells was measured and no significant cytotoxicity was observed in tested AuNPs
      concentration range. In the streptozotocin-induced diabetic rat model, the oral
      administration of AuNPs/INS exhibited an efficient regulation of glucose level,
      compared to INS solution-treated group. The mean INS concentration in plasma at
      120 min after oral administration of AuNPs/INS was 6.61-fold higher than that of
      INS solution-administered group. All of these findings indicate the successful
      application of CS-capped AuNPs for oral delivery of INS to the therapy of
      diabetes.

PMID- 24444887
TI  - In vitro and in vivo immunomodulatory activity of sulfated polysaccharides from
      red seaweed Nemalion helminthoides.
AB  - Water-soluble sulfated polysaccharides from the red seaweed Nemalion
      helminthoides: two xylomannan fractions (N3 and N4) and a mannan fraction (N6)
      were investigated to determine their in vitro and in vivo immunomodulatory
      activities. N3 and N4 induced in vitro proliferation of macrophages of the murine
      cell line RAW 264.7 and significantly stimulated the production of nitric oxide
      (NO) and cytokines (IL-6 and TNF-alpha) in the same cells, whereas this response
      was not observed with the mannan N6. The cytokine production was also stimulated
      by sulfated xylomannans in vivo in BALB/c mice inoculated intravenously with
      these polysaccharides. Remarkably, when mice were treated with N3 and N4 for 1 h
      before being infected with Herpes simplex virus type 2, they remained
      asymptomatic with no signs of disease. The in vitro and in vivo results suggest
      that sulfated xylomannans could be strong immunomodulators.

PMID- 24444888
TI  - Development of a feasible assay for the detection of GAA mutations in patients
      with Pompe disease.
AB  - BACKGROUND: Pompe disease is an inherited autosomal recessive deficiency of acid
      alpha-glucosidase (GAA) and is due to pathogenic sequence variants in the
      corresponding GAA gene. While the analysis of enzyme activity remains the
      diagnostic test of choice for individuals with Pompe disease, mutation analysis
      remains for establishing a definitive diagnosis. METHODS: High resolution melting
      (HRM) analysis was performed to screen GAA mutations. Genomic DNA was extracted
      from peripheral blood samples of the two patients with Pompe disease and 250
      normal controls. Exons 2 through 20 of the GAA gene were screened by the HRM
      analysis. The results were subsequently confirmed by direct sequencing. RESULTS:
      This assay proved to be feasible in detecting seven known (c.2T>C, c.1726G>A,
      c.1845G>A, c.1935C>A, c.1958C>A, c.2238G>C, and c.2815_2816del) GAA mutations.
      Each mutation could be readily and accurately identified in the difference plot
      curves. We estimated the carrier frequency of the most common mutation, c.1935G>A
      (p.D645E), in the Taiwanese population to be 0.2%. CONCLUSIONS: In clinical
      practice, we suggest that HRM analysis is assumed as a fast and reliable method
      for screening GAA gene mutations especially the most common mutations which are
      responsible for Pompe disease among the Taiwanese populations.

PMID- 24444889
TI  - Axially chiral biscarbazoles and biological evaluation of the constituents from
      Murraya koenigii.
AB  - Chemical investigation of the fruit pulp of Murraya koenigii resulted in the
      identification of two new dimeric carbazole alkaloids, bisgerayafoline D (1) and
      bismahanimbinol (2) along with four known alkaloids, bispyrayafoline (3), O
      methyl mahanine (4), O-methyl mukonal (5), and mahanine (6). Structures of 1-6
      were determined with the aid of UV, IR, Mass and extensive NMR spectroscopic
      studies. Absolute configurations of biaryls in 1 and 2 were assigned using a
      combination of computational Circular Dichroism (CD) and experimental electronic
      CD spectroscopic data. Compounds 1-6 were evaluated for anti-oxidant, anti-alpha
      glucosidase, DNA binding, protein interactions and cytotoxic activities. Among
      all the isolates, mahanine (6) was found to exhibit significant radical
      scavenging and alpha-glucosidase inhibitory activities. Compound 6 was also found
      to be active in cytotoxicity assay against three human cancer cell lines HeLa,
      HCT116, AGS and this compound was weakly active against normal mouse embryonic
      fibroblasts (NIH3T3). 

PMID- 24444890
TI  - Alkaloids from Coptis chinensis root promote glucose uptake in C2C12 myotubes.
AB  - The root of Coptis chinensis Franch. (COCH) is regularly used for medicinal
      purposes, and has been prescribed alone or in combination with other traditional
      herbs for the treatment of diabetes. To investigate the effects of COCH on
      glucose utilization by skeletal muscles, we prepared an ethanol extract of COCH
      root (COCH-Et) partitioned with dichloromethane, n-butanol, and water and tested
      its effects on glucose uptake in differentiated C2C12 myotubes. We found that
      dichloromethane and n-butanol sub-fractions of COCH-Et promoted glucose uptake in
      differentiated C2C12 cells at 50 MUg/mL. Further fractionation of these
      preparations by using column chromatography, analysis of their effects on glucose
      uptake and characterization using nuclear magnetic resonance, mass spectrometry,
      and thin layer chromatography helped identify two new alkaloids, 8,13
      dioxocoptisine hydroxide (1) and coptisonine (2), together with eleven known
      compounds. These were isolated from the dichloromethane layer of COCH-Et. In
      particular, exposure of C2C12 cells to berberine (6) at 12.5 and 6.25 MUg/mL for
      24h resulted in significant promotion of glucose uptake. Coptisonine (2) and
      octadecyl caffeate (9) also stimulated glucose uptake at 25 and 50 MUg/mL. These
      findings indicate that active constituents of COCH root may help alleviate
      hyperglycemia in diabetes by promoting glucose uptake by skeletal muscles.

PMID- 24444891
TI  - Five new cyotoxic steroidal glycosides from the fruits of Solanum torvum.
AB  - The fruits of Solanum torvum Swartz, commonly known as Turkey berry, are edible
      and commonly used as a vegetable in the South Indian population's diet and as an
      essential ingredient in Thai cuisine. Five new steroidal glycosides together with
      five known ones were isolated from the fruits of S. torvum Swartz. Based on
      chemical and spectral evidence, the five new compounds were identified to be
      25(S)-26-O-beta-D-glucopyranosyl-5alpha-furost-22(20)-en-3beta,6alpha,26-triol-6
      O-[alpha-L-rhamnopyranosyl-(1->3)-O-beta-D-quinovopyranoside] (1), 25(S)-26-O
      beta-D-glucopyranosyl-5alpha-furost-22(20)-en-3-one-6alpha,26-diol-6-O-[alpha-L
      rhamnopyranosyl-(1->3)-O-beta-D-quinovopyranoside] (2), 25(S)-26-O-beta-D
      glucopyranosyl-5alpha-furost-22(20)-en-3beta,6alpha,26-triol-6-O-beta-D
      quinovopyranoside (3), 5alpha-pregn-16-en-20-one-3beta,6alpha-diol-6-O-[alpha-L
      rhamnopyranosyl-(1->3)-beta-D-quinovopyranoside] (4), and 5alpha-pregn-16-en-3,20
      dione-6alpha-ol-6-O-[alpha-L-rhamnopyranosyl-(1->3)-beta-D-quinovopyranoside]
      (5). These new compounds were assayed for cytotoxicities in vitro, and 1 to 4
      showed cyotoxic activity against the human melanoma cell line A375, with IC50
      values of 30 MUM to 260 MUM.

PMID- 24444892
TI  - Th17/Treg imbalance in triptolide-induced liver injury.
AB  - The study was designed to investigate the immune-modulatory effects of triptolide
      (TP) on CD4(+) T cell responses during liver injury. Previous studies have
      suggested that TP plays a critical role in modulating both innate and adaptive
      immune reactions, but its effects on the Th17/Treg balance during TP-induced
      liver injury remain unknown. In this study, female C57BL/6 mice were administered
      by oral gavage with TP at a dose of 250 or 500 MUg/kg per mouse. We examined the
      plasma biochemical parameters, histopathological changes, hepatic frequencies of
      Th17 cells and Treg cells, hepatic expression of transcriptional factors and
      cytokine genes and hepatic interleukin (IL)-17 and IL-10 levels in TP
      administered mice. Mice treated with TP displayed liver injury with markedly
      increased plasma transaminase as well as hepatic mRNA expression of retinoid
      related orphan receptor (ROR)-gammat and hepatic IL-17 level at 24h. However,
      hepatic frequencies of Tregs and hepatic expression of forkhead/winged-helix
      family transcriptional repressor p3 (FoxP3) decreased at 24h after TP
      administration. Furthermore, we found that elevated serum biochemical parameters
      positively correlated with the Th17/Treg ratios. Taken together, these results
      revealed a novel and interesting phenomenon of TP in the enhancement of the
      expansion of Th17 cells and suppression of the production of Tregs during liver
      injury, which may represent a new pathogenesis of TP-induced liver injury.

PMID- 24444893
TI  - Chemical constituents of Lobelia chinensis.
AB  - Three new 2, 6-disubstituted piperidine alkaloids (1-3), one new polyacetylene
      (8), together with eight known compounds (4-7, 9-12) were isolated from the whole
      plants of Lobelia chinensis. Their structures were elucidated on the basis of
      spectroscopic data interpretation. The absolute configuration of 1 was
      established by a convenient Mosher ester procedure in which the sample was
      treated with MTPA chlorides in deuterated pyridine directly in NMR tube.
      Cytotoxicities of compounds 1-12 were tested against two human lung cancer cell
      lines, NCI-H292 and MSTO-211H. Compounds 8 and 9 exhibited moderate cytotoxic
      activity against the two cancer cell lines with the IC50 values in the range of
      9.31-12.36 MUM.

PMID- 24444894
TI  - Synthesis and antibacterial evaluation of 3-Farnesyl-2-hydroxybenzoic acid from
      Piper multiplinervium.
AB  - 3-Farnesyl-2-hydroxybenzoic acid is an antibacterial agent isolated from the
      leaves of Piper multiplinervium. This compound has activity against both Gram
      positive and Gram negative bacteria including Escherichia coli, Staphylococcus
      aureus and Helicobacter pylori. This research aimed to synthesize a natural
      antibacterial compound and its analogs. The synthesis of 3-Farnesyl-2
      hydroxybenzoic acid consists of three steps: straightforward synthesis involving
      protection of phenolic hydroxyl group, coupling of suitable isoprenyl chain to
      the protected aromatic ring at ortho position followed by carboxylation with
      concomitant deprotection to give the derivatives of the salicylic acid. All the
      three prenylated compounds synthesized were found to exhibit spectrum of activity
      against S. aureus (ATCC) having MIC: 5.84*10(-3), 41.46*10(-2) and 6.19*10(-1)
      MUmol/ml respectively. The compounds also displayed activity against resistance
      strain of S. aureus (SA1119B) having MIC: 5.84*10(-3), 7.29*10(-3) and 3.09*10(
      1) MUmol/ml respectively. This synthesis has been achieved and accomplished with
      the confirmation of it structure to that of the original natural product, thus
      producing the first synthesis of the natural product and providing the first
      synthesis of its analogs with 3-Farnesyl-2-hydroxybenzoic acid having biological
      activity higher than that of the original natural product.

PMID- 24444895
TI  - Biflavanones with anti-proliferative activity against eight human solid tumor
      cell lines from Stellera chamaejasme.
AB  - Six 3,3"-biflavanones, including a new compound isochamaejasmenin C (1), were
      isolated from EtOH extracts of the roots of Stellera chamaejasme L. Their
      structures were elucidated on the basis of spectroscopic methods, including HR
      ESI-MS and 2D NMR techniques. The absolute configurations on 2, 3, 3", and 2" of
      compounds 1, 3, and 6, which represent three geometry types of these compounds,
      were determined by TDDFT quantum chemical calculations of their ECD spectra. All
      compounds were evaluated for their cytotoxicities against eight human solid tumor
      cell lines and compounds 2, 4, and 6 showed strong anti-proliferative effects
      against all these cell lines with IC50 values ranging from 1.08 to 15.97 MUM,
      which were in the same range as the positive control paclitaxel.

PMID- 24444896
TI  - Septic pericarditis and myocardial abscess in an English Springer spaniel.
AB  - Septic pericarditis and myocardial abscess are rare conditions in dogs. They are
      usually caused by foreign bodies, penetrating wounds, systemic infections or
      extension of local infections such as endocarditis, pleuritis or pulmonary
      infections to the myocardial tissue. Here we report a septic pericardial effusion
      and myocardial abscess in a young English Springer spaniel presenting with a long
      history of pyrexia and lethargy. No cause could clearly be identified although a
      penetrating injury or dissolving foreign body was highly suspected. The patient
      was successfully treated with a surgical approach in combination with broad
      spectrum antibacterials resulting in resolution of clinical signs without
      recurrence of the infection. 

PMID- 24444897
TI  - Symmetrisation procedures in breast reconstruction patients constitute a rising
      workload in our DGH.
AB  - INTRODUCTION: In breast cancer patients undergoing reconstructive surgery,
      achieving symmetry is of considerable importance. The aim of our study was to
      identify the proportion of breast cancer patients undergoing reconstructive
      surgery requiring contralateral symmetrisation procedures. PATIENTS AND METHODS:
      This is a retrospective review of consecutive patients undergoing reconstructive
      procedures following cancer surgery from April 2005 to April 2012. RESULTS: One
      hundred and fifty three patients had symmetrisation procedure of the opposite
      side during this period. The median age was 53 years (22-79). Reduction
      mammoplasty was the commonest procedure (94 patients), followed by mastopexy (34
      patients) and augmentation mammoplasty (25 patients). Overall, it represent
      approximately one third of (153/489; 31.2%) of all the major reconstruction
      procedures in this unit. CONCLUSION: Almost half the number of patients (153/336)
      undergoing breast reconstruction as a part of breast cancer surgery had a
      symmetrisation procedure performed on the opposite side which constitutes a
      significant reconstructive workload in our unit. Consideration should be given to
      the above when planning departmental work force and training.

PMID- 24444898
TI  - Fluorescent boronic acid polymer grafted on silica particles for affinity
      separation of saccharides.
AB  - Boronic acid affinity gels are important for effective separation of biological
      active cis-diols, and are finding applications both in biotech industry and in
      biomedical research areas. To increase the efficacy of boronate affinity
      separation, it is interesting to introduce repeating boronic acid units in
      flexible polymer chains attached on solid materials. In this work, we synthesize
      polymer brushes containing boronic acid repeating units on silica gels using
      surface-initiated atom transfer radical polymerization (ATRP). A fluorescent
      boronic acid monomer is first prepared from an azide-tagged fluorogenic boronic
      acid and an alkyne-containing acrylate by Cu(I)-catalyzed 1,3-dipolar
      cycloaddition reaction (the CuAAC click chemistry). The boronic acid monomer is
      then grafted to the surface of silica gel modified with an ATRP initiator. The
      obtained composite material contains boronic acid polymer brushes on surface and
      shows favorable saccharide binding capability under physiological pH conditions,
      and displays interesting fluorescence intensity change upon binding fructose and
      glucose. In addition to saccharide binding, the flexible polymer brushes on
      silica also enable fast separation of a model glycoprotein based on selective
      boronate affinity interaction. The synthetic approach and the composite
      functional material developed in this work should open new opportunities for high
      efficiency detection, separation, and analysis of not only simple saccharides,
      but also glycopeptides and large glycoproteins. 

PMID- 24444899
TI  - Food-related applications of Yarrowia lipolytica.
AB  - Yarrowia lipolytica is a non-pathogenic generally regarded as safe yeast. It
      displays unique physiological as well as biochemical properties that are relevant
      in food-related applications. Strains naturally associated with meat and dairy
      products contribute towards specific textures and flavours. On some occasions
      they cause food spoilage. They produce food-additives such as aroma compounds,
      organic acids, polyalcohols, emulsifiers and surfactants. The yeast biomass has
      been projected as single cell oil and single cell protein. Y. lipolytica degrades
      or upgrades different types of food wastes and in some cases, value-added
      products have also been obtained. The yeast is thus involved in the manufacture
      of food stuffs, making of food ingredients, generation of biomass that can be
      used as food or feed and in the effective treatment of food wastes. On account of
      all these features, this versatile yeast is of considerable significance in food
      related applications. 

PMID- 24444900
TI  - Brown seaweed (Saccharina japonica) as an edible natural delivery matrix for
      allyl isothiocyanate inhibiting food-borne bacteria.
AB  - The edible, brown seaweed Saccharina japonica was prepared as powder in the size
      range 500-900 MUm for the desorption release of allyl isothiocyanate (AITC).
      Powders were used as raw (containing lipids) and as de-oiled, where the lipid was
      removed. In general, de-oiled powders adsorbed larger masses of AITC after vapour
      or solution contact. Mass adsorbed due to solution contact exceeded vapour
      contact. Larger particles adsorbed more than smaller particles. No chemical
      bonding between AITC and the powder surface occurred. Release from vapour
      deposited particles reached 70-85% available within 72 h; solution deposited
      reached 70-90% available at 192 h. The larger amounts of AITC adsorbed via
      solution deposition resulted in greater vapour-phase concentrations at 72 h for
      antimicrobial activity studies. No loss of activity was detected against
      Escherichia coli, Salmonella Typhimurium or Bacillus cereus. Only a nominal
      activity against Staphylococcus aureus was demonstrated. S. japonica powder could
      be used as an edible, natural vehicle for AITC delivery.

PMID- 24444901
TI  - Residues, dissipation and safety evaluation of chromafenozide in strawberry under
      open field conditions.
AB  - The dissipation and residual levels of new generation insecticide chromafenozide
      in strawberries under field conditions were studied using HPLC-DAD after QuEChERS
      extraction. The method was validated using blank samples spiked at three levels
      and the results showed that recoveries ranged from 99% to 110%. The intra- and
      inter-day relative standard deviations were less than 7.5% and 9.2%,
      respectively. Estimated limit of detection and limit of quantification for
      chromafenozide were 0.003 and 0.01 mg/kg, respectively. The residues of
      chromafenozide were found to dissipate following first order kinetics and its
      half-life ranged from 3.53 to 4.07 days. The results showed that the use of
      chromafenozide at recommended dose does not pose any hazards to consumers. These
      results can be utilised in formulating spray schedules and safety evaluation for
      chromafenozide insecticide in strawberry.

PMID- 24444902
TI  - Anti-inflammatory cyclopeptides from exocarps of sugar-apples.
AB  - Two new cyclic peptides, fanlizhicyclopeptide A, cyclo(Pro(1)-Pro(2)-Tyr(3)
      Leu(4)-Pro(5)-Gly(6)-Val(7)) (1), and fanlizhicyclopeptide B, cyclo(Pro(1)-Ile(2)
      Tyr(3)-Ala(4)-Gly(5)) (2), were isolated along with six known kaurane
      diterpenoids and a known clovane sesquiterpene from the exocarps of sugar-apples,
      the fruit of Annona squamosa. Their structures were elucidated by ESI MS/MS
      experiments, 1D and 2D NMR data and chemical degradation. In the anti
      inflammatory assay, both 1 and 2 showed in vitro inhibitory effects on the
      production of pro-inflammatory cytokines, TNF-alpha and IL-6, in LPS-stimulated
      RAW 264.7 macrophages. 

PMID- 24444903
TI  - Free and glycosidically bound aroma compounds in cherry (Prunus avium L.).
AB  - This paper reports the occurrence of both free and glycosidically bound aroma
      compounds in three sweet cherry cultivars ('Hongdeng', 'Hongyan' and 'Rainier'),
      with 97 compounds being identified in the three cultivars. The major free
      volatile compounds found were hexanal, (E)-2-hexenal, (E)-2-hexen-1-ol, benzyl
      alcohol and benzaldehyde. The major bound volatile compounds found were benzyl
      alcohol, geraniol, 2-phenylethanol. Also 4-vinylphenol was found in cherry fruit
      for the first time, and has a relatively high concentration of the glycosidically
      bound form in 'Rainier'. Odour activity values (OAVs) were determined for both
      free and bound volatiles, with 18 compounds having an OAV above 1. The highest
      OAVs for three cultivars were (E)-beta-ionone, hexanal, decanal and (E)-2-hexenal
      with the highest being over 800 for (E)-beta-ionone in 'Honyang'. From these
      results, it was concluded that the aroma compounds present were similar in all
      three cultivars, but there was significant variation found in their levels and
      hence contribution to the aroma of these cultivars. 

PMID- 24444904
TI  - Effect of microfluidisation on antioxidant properties of corn bran.
AB  - The microfluidisation process was used to reduce the particle size and loosen the
      tight microstructure of corn bran. This process significantly increased corn
      bran's antioxidant activity exhibited through a surface reaction phenomenon and
      the extractability of phenolic compounds after alkaline and acid hydrolysis. For
      corn bran microfluidised through an 87 MUm interaction chamber for 5 passes, the
      two most largely increased phenolic acids released after alkaline hydrolysis were
      p-coumaric acid (51.1%) and ferulic acid (45.1%). On the other hand, high shear
      stress during microfluidisation caused partial dispersion or dissolution of free
      phenolic compounds in water which was lost after the process. It was also found
      that bran residues after alkaline and acid hydrolysis still exhibited strong
      antioxidant activity via a surface reaction phenomenon, probably indicating the
      conventional method based on solvent extraction and relatively mild alkaline
      and/or acid hydrolysis underestimates the total phenolic content and antioxidant
      activity of corn bran.

PMID- 24444905
TI  - Bound phenolics in foods, a review.
AB  - Among phytochemicals, phenolic compounds have been extensively researched due to
      their diverse health benefits. Phenolic compounds occur mostly as soluble
      conjugates and insoluble forms, covalently bound to sugar moieties or cell wall
      structural components. Absorption mechanisms for bound phenolic compounds in the
      gastrointestinal tract greatly depend on the liberation of sugar moieties. Food
      processes such as fermentation, malting, thermoplastic extrusion or enzymatic,
      alkaline and acid hydrolyses occasionally assisted with microwave or ultrasound
      have potential to release phenolics associated to cell walls. Different kinds of
      wet chemistry methodologies to release and detect bound phenolic have been
      developed. These include harsh heat treatments, chemical modifications or
      biocatalysis. New protocols for processing and determining phenolics in food
      matrices must be devised in order to release bound phenolics and for quality
      control in the growing functional food industry. 

PMID- 24444906
TI  - Optimisation of soy flour fermentation parameters to produce beta-glucosidase for
      bioconversion into aglycones.
AB  - The solid state fermentation (SSF) parameters of defatted soybean flour (DSF)
      with Aspergillus oryzae IOC 3999/1998 or Monascus purpureus NRRL 1992 was
      evaluated using a rotational central composite experimental design to optimise
      the production of beta-glucosidase and convert glycosidic isoflavones in
      aglycones. Variables investigated were initial pH of DSF, volume of water added
      to 10 g of DSF and incubation temperature. beta-Glucosidase activity was measured
      using the synthetic substrate, p-nitrophenyl-beta-D-glucoside. The content of
      isoflavones was determinate by ultra performance liquid chromatography. The
      highest production of beta-glucosidase for both strains occurred when adding 10
      mL of water to the DSF, incubating at 30  degrees C and using 6.0 as the initial
      DSF pH. A. oryzae IOC 3999/1998 expressed beta-glucosidase activity at 10.7 times
      higher than M. purpureus NRRL 1992. The DSF fermentation was more efficient in
      converting isoflavones with M. purpureus NRRL 1992.

PMID- 24444907
TI  - Optimized extraction, separation and quantification of twelve intact
      glucosinolates in broccoli leaves.
AB  - A new method has been developed and validated to determine twelve intact
      glucosinolates (glucoiberin, GIB; glucoraphanin, GRA; glucoerucin GER;
      gluconapin, GNA; glucotropaeolin, GTL; glucobrassicin, GBC; gluconasturtiin, GST;
      glucoalyssin, ALY; 4-hydroxyglucobrassicin, 4-OH; 4-metoxyglucobrassicin, 4ME;
      neoglucobrassicin, NEO; sinigrin, SIN) in broccoli leaves using liquid
      chromatography (LC) coupled to diode array (DAD) and electrospray ionization mass
      spectrometry (ESI-MS) detection. An extraction procedure has also been proposed
      and optimized by means of statistical analysis (the Box-Behnken design and
      analysis of variance); this is based on the deactivation of myrosinase using a
      microwave and heated water. Low limits of detection and quantification were
      obtained, ranging from 10 to 72 MUg/g with DAD and 0.01 to 0.23 MUg/g with ESI
      MS, and the resulting recovery values ranged from 87% to 106% in all cases.
      Finally, glucosinolates were analyzed in broccoli leaf samples from six different
      cultivars (Ramoso calabrese Parthenon, Marathon, Nubia, Naxos and Viola).

PMID- 24444908
TI  - Polyhydroxybutyrate-b-polyethyleneglycol block copolymer for the solid phase
      extraction of lead and copper in water, baby foods, tea and coffee samples.
AB  - A new adsorbent, polyhydroxybutyrate-b-polyethyleneglycol, was used for the
      separation and preconcentration of copper(II) and lead(II) ions prior to their
      flame atomic absorption spectrometric detections. The influences of parameters
      such as pH, amount of adsorbent, flow rates and sample volumes were investigated.
      The polymer does not interact with alkaline, alkaline-earth metals and transition
      metals. The enrichment factor was 50. The detection limits were 0.32 MUg L(-1)
      and 1.82 MUg L(-1) for copper and lead, respectively. The recovery values were
      found >95%. The relative standard deviations were found to be less than 6%. The
      validation of the procedure was performed by analysing certified reference
      materials; NIST SRM 1515 Apple leaves, IAEA-336 Lichen and GBW-07605 Tea. The
      method was successfully applied for the analysis of analytes in water and food
      samples.

PMID- 24444909
TI  - Determination of calcium disodium ethylenediaminetetraacetate (E385) in marketed
      bottled legumes, artichokes and emulsified sauces by gas chromatography with mass
      spectrometric detection.
AB  - An original method to determine the food additive calcium disodium
      ethylenediaminetetraacetate in bottled food is proposed. The method involves the
      solid-liquid extraction of a portion of the whole content of legume or artichoke
      bottles, or the dilution of sauce samples, with water followed by an evaporation
      step by heating. Finally, ethylenediaminetetraacetic acid is methylated and
      determined by GC. Recoveries obtained on spiked samples were acceptable (96-108%)
      with RSDs comprised from 4.3% to 10%. Results suggest that the determination of
      additive only in the liquid phase of legume or artichoke bottles is not suitable
      to know its total amount because the additive is distributed between the liquid
      and solid phases. The contribution of each step of the analytical method to the
      uncertainty of the measured concentration has been assessed by a "bottom-up"
      approach, including the heterogeneity of the sample which resulted to be very
      variable after studying twenty samples. 

PMID- 24444910
TI  - Comprehensive two-dimensional gas chromatography for determination of the
      terpenes profile of blue honeysuckle berries.
AB  - Terpenes are the main group of secondary metabolites, which play essential role
      in human. The establishment of the terpenes profile of berries of different blue
      honeysuckle cultivars was achieved by headspace solid-phase microextraction
      coupled with comprehensive two-dimensional gas chromatography with time-of-flight
      mass spectrometry (HS-SPME/GC*GC-TOFMS). The berries were found to contain 44
      terpenes identified by GC*GC-TOFMS. From these, 10 were previously reported in
      blueberries. According to their chemical structure, the compounds were organised
      in different groups: monoterpene hydrocarbons and monoterpene oxygen-containing
      compounds (oxides, alcohols, aldehydes, and ketones). Positive identification of
      some of the compounds was performed using authentic standards, while tentative
      identification of the compounds was based on deconvoluted mass spectra and
      comparison of linear retention indices (LRI) with literature values. The major
      components of volatile fraction were monoterpenes, such as eucalyptol, linalool
      and p-cymene. Furthermore, quantitative analysis showed that eucalyptol was the
      most abundant bioactive terpene in analysed berries (12.4-418.2 MUg/L).

PMID- 24444911
TI  - Novel application of NMR relaxometry in studies of diffusion in virgin rape oil.
AB  - Field cycling (FC) proton nuclear magnetic resonance ((1)H NMR) relaxometry was
      applied to study the dynamics of rape oil molecules. The spin-lattice relaxation
      data, measured in the frequency range from 0.01 to 30 MHz, were analysed by
      applying relaxation theory combined with the force-free-hard-sphere (FFHS)
      diffusion model. In the low frequency range, the relaxation was dominated by the
      translational diffusion contribution. Therefore, the diffusion coefficient of
      rape oil was determined from a linear dependence of the (1)H NMR relaxation
      dispersion drawn as a function of the square root of Larmor frequency. The
      results are consistent with those obtained from the pulse gradient spin echo
      (PGSE) NMR method. To estimate the density of oil protons, a parameter required
      to derive the diffusion coefficient from NMR relaxometry, a single point imaging
      (SPI) NMR experiment was proposed.

PMID- 24444912
TI  - A grape and wine chemodiversity comparison of different appellations in Burgundy:
      vintage vs terroir effects.
AB  - This study aimed at assessing the ability of high resolution Fourier Transform
      Ion Cyclotron Resonance - Mass Spectrometry (FTICR-MS) to differentiate grapes
      and corresponding wines from distinct vineyards managed by a same producer,
      according to complex chemical fingerprints. Grape extracts (at harvest) and
      corresponding wines from four different vineyards, sampled immediately after the
      alcoholic fermentation over three successive vintages, were analysed by FTICR-MS.
      Thousands of metabolites that are specific to a given vintage, or a given class
      (wine, skin or must) could be revealed, thus emphasising a strong vintage effect.
      The same wines were reanalyzed after a few years in bottle. Within the frame of
      this study, FTICR-MS along with multivariate statistical analyses could reveal
      significant terroir-discriminant families of metabolites from geographically
      close - though distinct - vineyards, but only after a few years of bottle ageing.
      It is supposed that the chemical composition of a wine holds memories of various
      environmental factors that have impacted its metabolic baggage at the moment of
      its elaboration. For the first time, such preliminary results indicate that non
      targeted experiments can reveal such memories through terroir-related metabolic
      signatures of wines on a regional-scale that can potentially be as small as the
      countless "climats" of Burgundy. 

PMID- 24444914
TI  - Branch chain elongation by amylosucrase: production of waxy corn starch with a
      slow digestion property.
AB  - Starches with high slowly digestible starch (SDS) contents were prepared by
      treating completely gelatinized waxy corn starch with amylosucrase. The
      structural properties of the prepared starches were then investigated. The
      content of SDS increased by up to 38.7% after amylosucrase modification, and the
      portion of chains with degree of polymerisation (DP) 25-36 increased, while the
      portion of chains with DP?12 decreased. Amylosucrase-modified starches showed a
      weak B-type crystalline structure. A slight increase in the degree of relative
      crystallinity was observed with increased reaction time. The thermal properties,
      including melting temperature and enthalpy, of the amylosucrase-modified starches
      were higher than for the control starch. Although the amylosucrase-modified
      starches showed varying structural properties according to reaction time (1-45
      h), their digestibilities did not change much after 6 h. By controlling the
      reaction time of the amylosucrase treatment, a tailored starchy food containing
      the desired amount of SDS can be produced.

PMID- 24444915
TI  - Evaluation of different methods for determination of the iron saturation level in
      bovine lactoferrin.
AB  - Lactoferrin (Lf) samples with ca. 25%, 50%, 75%, 85% and 100% iron saturation
      were prepared for the purpose of evaluating Chromametry, Differential Scanning
      Calorimetry (DSC) and Circular Dichroism (CD) spectropolarimetry for their
      suitability in determining the iron saturation level. Numerical values for colour
      from Chromametry, enthalpy change of denaturation (DeltaHcal) from DSC and molar
      ellipticities from CD were statistically analysed to evaluate their correlation
      with the level of iron saturation in Lf. Linear regression analysis of colour
      coordinates Chroma (C(*)) and hue (h degrees ) angle on percentage iron
      saturation level of Lf showed that the values can be used to estimate the iron
      saturation level. The DeltaHcal for the iron saturated peak and the CD
      ellipticities in the 310-340 nm region provided reliable data for the estimation
      of iron saturation level of Lf up to 75%. Mono- and di-saturated Lf displayed the
      same thermal stability and very similar tertiary structures.

PMID- 24444913
TI  - Formation of ethyl carbamate and changes during fermentation and storage of
      yellow rice wine.
AB  - Ethyl carbamate (EC) was analyzed during yellow rice wine production and storage.
      EC increased slowly during fermentation and rapidly after frying and
      sterilization. Less amount of EC was formed when cooled rapidly to 30  degrees C
      than when cooled naturally. High temperature and long storage time increased EC
      formation. After 400 days storage, EC increased from 74.0 to 84.2, 131.8 and
      509.4 MUg/kg at 4  degrees C, room temperature and 37  degrees C, respectively,
      and there was significantly difference between the fried wine and the wine on
      sale from 2011 (p<0.01). Urea increased during yellow rice wine fermentation and
      was above 20 mg/kg after the wine was fried; urea contributed to EC formation
      when the fried wine was cooled slowly. These results indicate that it is
      necessary for industry to optimize the wine frying conditions, such as
      temperature, time and cooling process in order to decrease EC formation.

PMID- 24444916
TI  - Improved the slow digestion property of maize starch using partially beta
      amylolysis.
AB  - In this study, partial beta-amylolysis was used to modulate the starch fine
      structure responsible for the slow digestion property of starch. Normal maize
      starch modified using beta-amylase for 2 h showed an increase of slowly
      digestible starch from 11.16% to 24.38%. The beta-amylase treatment increased the
      amylose content from 28.4% to 32.5%, decreased the molecular weight from
      32.5*10(7) to 3.8*10(5) g/mol and increased the number of shorter chains (DP<13)
      from 25.5% to 41.1%, accompanied by a reduction of longer chains (DP>13). (1)H
      NMR spectra showed an increase of alpha-1,6 linkages from 7.4% to 10.1% in the
      enzyme treated starches. Both the increase in the amount of shorter chains and
      the increase in alpha-1,6 linkages were attributed to the slow digestion property
      of starch. These results suggest that starches treated with partial beta
      amylolysis retain a branched structure and slow digestibility.

PMID- 24444917
TI  - Amygdalin content of seeds, kernels and food products commercially-available in
      the UK.
AB  - Cyanogenic glycosides are a large group of secondary metabolites that are widely
      distributed in the plant kingdom, including many plants that are commonly
      consumed by humans. The diverse chemical nature of cyanogenic glycosides means
      that extraction and analysis of individual compounds can be difficult. In
      addition, degradation can be rapid under appropriate conditions. Amygdalin is one
      of the cyanogenic glycosides found, for example, in apples, apricots and almonds.
      We have developed and applied a high performance liquid chromatographic procedure
      for amygdalin quantification to investigate extraction efficiency and to
      determine levels in a range of commercially-available foods for the first time.
      Our results show that seed from Rosaceae species contained relatively high
      amounts (range 0.1-17.5 mg g(-1)) of amygdalin compared to seed from non-Rosaceae
      species (range 0.01-0.2 mg g(-1)). The amygdalin content of processed food
      products was very low.

PMID- 24444918
TI  - Characterization of an inclusion complex of ethyl benzoate with hydroxypropyl
      beta-cyclodextrin.
AB  - The inclusion complex of ethyl benzoate with hydroxypropyl-beta-cyclodextrin
      (HPCD) was prepared by a freeze-drying method and its characterizations were
      investigated by different analytical techniques including UV, FT-IR and phase
      solubility methods. All these approaches indicated that ethyl benzoate was able
      to form an inclusion complex with HPCD, and the ethyl benzoate/HPCD inclusion
      compounds exhibited different spectroscopic features and properties from ethyl
      benzoate. The stoichiometry of the complex was 1:1 and it was the benzene ring
      part of the ethyl benzoate molecule included into the HPCD cavities from the
      wider edge. The calculated apparent stability constant of the complex was 9485 M(
      1). Moreover, the water solubility of ethyl benzoate was significantly improved
      by phase solubility studies. The release of ethyl benzoate was also regulated by
      the form of the inclusion complex. The results showed that HPCD was a proper
      excipient for increasing the solubility and controlled release of ethyl benzoate.

PMID- 24444919
TI  - The initial characteristics of marine oil emulsions and the composition of the
      media inflect lipid oxidation during in vitro gastrointestinal digestion.
AB  - This work aimed at evaluating the effect of simulated digestive fluids, interface
      and lipid droplet sizes on the oxidation of oil-in-water emulsions containing
      long chain n-3 fatty acyls. Emulsions stabilised by a protein or by phosphatidyl
      choline/Tween 80 were submitted to gastro-intestinal in vitro conditions in
      presence of metmyoglobin. The gastric phase was characterised by a decrease of
      tocopherol amounts and moderate O2 uptake and aldehyde formation. Oxidation
      developed further during the intestinal phase, with tocopherols tending to zero,
      oxygen uptake and production of aldehydes at potentially toxic concentrations.
      The simulated digestive fluids reduced oxygen uptake and MDA formation only
      during the intestinal step of the phospholipid-stabilised emulsion. Quantitative
      losses of PUFA (e.g. EPA, DHA) were less than 10% even significant at the end of
      the digestion. 

PMID- 24444920
TI  - Determination of the total polyphenolic content in Cirsium palustre (L.) leaves
      extracts with manganese(IV) chemiluminescence detection.
AB  - It was found that weak chemiluminescence of manganese(IV)-hexametaphosphate
      formaldehyde system was greatly enhanced by plant polyphenolic compounds. Based
      on this finding, a new flow injection chemiluminescence method (FI-CL) was
      developed for the determination of the total content of polyphenols in plant
      extracts. The calibration graph obtained for standard solutions of 6
      hydroxyluteolin 7-O-glucoside (6OHLG) was linear in the range 0.001-0.8 MUg mL(
      1). The method was simple, rapid (203 samples h(-1)) and sensitive with a
      detection limit of 0.25 ng mL(-1). The FI-CL method was successfully applied to
      the determination of the total polyphenols content (as 6OHLG equivalents) in
      methanolic, ethyl acetate and aqueous extracts from leaves of Cirsium palustre
      (L.). Two types of solvent extraction methods (reflux and ultrasound assisted
      extraction) were used and compared in terms of extraction efficiency. A positive,
      significant linear correlation between the results obtained by FI-CL method and
      spectrophotometric methods was observed.

PMID- 24444921
TI  - Use of winemaking by-products as an ingredient for tomato puree: the effect of
      particle size on product quality.
AB  - Formulations of tomato puree with grape skin fibres (Chardonnay variety) having
      varying particle sizes were studied. The contents of flavonoids (by HPLC-DAD) and
      proanthocyanidins (n-butanol/HCl assay), reducing capacity (ferric ion reducing
      antioxidant power, FRAP) and anti-glycation activity by a bovine serum albumin
      (BSA)/fructose model system were analysed in vitro. A liking test was performed
      with consumers. Stabilization was carried out by either an intensive autoclave
      treatment or an optimised microwave-treatment achieving 6D-reduction of the
      target microorganism (Alicylobacillus acidoterrestris). In the fortified tomato
      purees, the solubility of proanthocyanidins decreased, but was partly restored by
      autoclave treatment, which also caused deglycosylation of flavonol glycosides.
      Microwave treatment did not show any effect on phenolics. The reducing capacity
      and ability to inhibit protein glycation greatly increased in the fortified
      purees. The particle sizes of solids in the formulations played a major role with
      respect to the consumers' liking, with the smallest fraction showing maximum
      ratings. 

PMID- 24444922
TI  - Production of bioactive cyathane diterpenes by a bird's nest fungus Cyathus
      gansuensis growing on cooked rice.
AB  - Cyathane diterpenes are important bioactive substances produced by some edible
      and medicinal fungi. Seven new cyathane type diterpenes, named as cyathins J-P (1
      7), together with two known diterpenes (8 and 9), were isolated from the solid
      culture of the bird's nest fungus Cyathus gansuensis growing on cooked rice. The
      structures of the new secondary metabolites were elucidated by NMR experiments.
      Bioactivity screening indicated that compounds 1, 2, 4, and 8 showed moderate
      inhibitory activity against NO production in lipopolysaccharide-activated
      macrophages with an IC50 value of 42, 78, 80, and 16 MUM, respectively. The
      fungus C. gansuensis is a promising source of bioactive secondary metabolites and
      has application potential in preparing healthy food.

PMID- 24444923
TI  - Preparation and characterization of modified starch granules with high
      hydrophobicity and flowability.
AB  - Normal cornstarch (NC) was chemically modified by octenylsuccinic anhydride (OSA)
      and Al2(SO4)3. The effects of the concentration of NaOH, OSA, and Al2(SO4)3 on
      the properties of modified starch(OS-starch-Al) were investigated. The OS-starch
      Al was characterized by repose angle, activation index, inductively coupled
      plasma-atomic emission spectrometry (ICP-OES), light microscopy, SEM, FT-IR, and
      (27)Al NMR. The results showed that pH 4 was the optimum condition for Al(3+)
      cross-linking with OS-starch and for obtaining high flowability and
      hydrophobicity. When the concentration of OSA and Al2(SO4)3 was 2%, the OS-starch
      Al was characterized by high flowability. A concentration of 4% OSA and Al2(SO4)3
      yielded the highest activation index. The moisture content affected the
      flowability of native NC, but had a minor effect on OS-starch-Al. SEM and
      polarized microscopy revealed that the modification had slight effects on the
      crystalline structure and morphology of NC. During the preparation, some dust
      particles functioning as flow additives were produced on the surface of starch
      granules. The results of FT-IR, ICP-OES, and (27)Al NMR confirmed the formation
      of ester group and the cross-link with Al(3+). 

PMID- 24444924
TI  - Effect of whole wheat flour on the quality of traditional Chinese Sachima.
AB  - The effects of whole wheat flour (WWF) on the properties of the dough and the
      final quality of Sachima were investigated. Refined wheat flour (RWF) in the
      recipe for Sachima dry mix was replaced with WWF at different levels. The
      farinograph characteristics of the Sachima dough were significantly weakened by
      adding WWF, except for the water absorption ability. The dough extensibility was
      also weakened by adding WWF, while the values of resistance to a certain
      extension increased. WWF enhanced the fried crust hardness and breaking force and
      darkened the surface colour with lower L(*) and higher a(*) values. The puffing
      quality was negatively affected by WWF with a decreased specific volume. The
      structural oil content in fried Sachima sticks was reduced by 34.86% compared
      with the control. In conclusion, WWF can be used in Sachima to partially
      substitute RWF to produce a lower oil content Sachima. 

PMID- 24444925
TI  - Topsoil drying combined with increased sulfur supply leads to enhanced aliphatic
      glucosinolates in Brassica juncea leaves and roots.
AB  - The decrease of water availability is leading to an urgent demand to reduce the
      plants' water supply. This study evaluates the effect of topsoil drying, combined
      with varying sulfur (S) supply on glucosinolates in Brassica juncea in order to
      reveal whether a partial root drying may already lead to a drought-induced
      glucosinolate increase promoted by an enhanced S supply. Without decreasing
      biomass, topsoil drying initiated an increase in aliphatic glucosinolates in
      leaves and in topsoil dried roots supported by increased S supply.
      Simultaneously, abscisic acid was determined, particularly in dehydrated roots,
      associated with an increased abscisic acid concentration in leaves under topsoil
      drying. This indicates that the dehydrated roots were the direct interface for
      the plants' stress response and that the drought-induced accumulation of
      aliphatic glucosinolates is related to abscisic acid formation. Indole and
      aromatic glucosinolates decreased, suggesting that these glucosinolates are less
      involved in the plants' response to drought. 

PMID- 24444926
TI  - Feasibility of using hyperspectral imaging to predict moisture content of porcine
      meat during salting process.
AB  - The feasibility of using hyperspectral imaging technique (1000-2500 nm) for
      predicting moisture content (MC) during the salting process of porcine meat was
      assessed. Different spectral profiles including reflectance spectra (RS),
      absorbance spectra (AS) and Kubelka-Munk spectra (KMS) were examined to
      investigate the influence of spectroscopic transformations on predicting moisture
      content of salted pork slice. The best full-wavelength partial least squares
      regression (PLSR) models were acquired based on reflectance spectra (Rc(2)=0.969,
      RMSEC=0.921%; Rc(2)=0.941, RMSEP=1.23%). On the basis of the optimal wavelengths
      identified using the regression coefficient, two calibration models of PLSR and
      multiple linear regression (MLR) were compared. The optimal RS-MLR model was
      considered to be the best for determining the moisture content of salted pork,
      with a Rc(2) of 0.917 and RMSEP of 1.48%. Visualisation of moisture distribution
      in each pixel of the hyperspectral image using the prediction model display
      moisture evolution and migration in pork slices.

PMID- 24444927
TI  - Anthocyanin contributes more to hydrogen peroxide scavenging than other phenolics
      in apple peel.
AB  - The phenolic compounds in apple peel extracts were quantified in the presence of
      hydrogen peroxide (H2O2) to identify which phenolic compound contributed more to
      H2O2 scavenging. The results showed that the phenolics extracted from 'Golden
      Delicious' apple peel had a strong ability for scavenging H2O2. After incubating
      with H2O2 for 30 min, cyanidin-3-galactoside concentrations in the phenolic
      extract decreased as H2O2 concentrations increased. In contrast, the
      concentrations of other phenolic compounds remained unchanged. Exogenous
      application of H2O2 enhanced the synthesis of phenolics, especially anthocyanin,
      in 'Golden Delicious' apple peel under sunlight. After incubating the peel
      extract of H2O2-treated apples in the dark for 30 min, the concentration of
      cyanidin-3-galactoside significantly decreased to a greater extent than that of
      other phenolic compounds. Based on these data, anthocyanin is more sensitive to
      H2O2 and contributes more to H2O2 scavenging than other phenolic compounds.

PMID- 24444928
TI  - Effects of processing with dry heat and wet heat on the antioxidant profile of
      sorghum.
AB  - The effects of domestic processing with dry heat (F2-oven/milling; F3
      milling/oven; F4-microwave oven/milling; F5-milling/microwave oven; F6-popped
      grains/milling) and wet heat (F7-cooking in water/drying/milling) on the
      antioxidant profile of sorghum flours (F1-raw flour) were evaluated. 3
      Deoxyanthocyanidins and total phenolic compounds were stable to dry heat
      (retention between 96.1% and 106.3%) and reduced with wet heat. All processing
      with dry heat increased the vitamin E content (2,201.9-3,112.1 MUg/100 g) and its
      retention, and reduced the carotenoids (4.78-17.27 MUg/100 g). The antioxidant
      activity in processed flours with dry heat remained constant (F3 and F6) or
      increased (F2, F4 and F5) and decreased after processing with wet heat. Overall,
      the grains milled before processing in oven and in microwave oven retained more
      vitamin E and less carotenoids than those milled after these processing. In
      conclusion, dry heat did not affect the phenolic compounds and 3
      deoxyanthocyanidins of sorghum, but increased the vitamin E and antioxidant
      activity, and reduced the carotenoids. The wet heat processing reduced all
      antioxidant compounds except carotenoids, which increased.

PMID- 24444929
TI  - Identification of peptides from soybean protein, glycinin, possessing suppression
      of intracellular Ca2+ concentration in vascular smooth muscle cells.
AB  - In this study, we challenged to identify vasoactive peptides in soybean 11S
      glycinin hydrolysate by thermolysin to regulate intracellular Ca(2+)
      concentration ([Ca(2+)]i) that can induce constrictive vascular tension. As a
      function of the inhibition of elevated [Ca(2+)]i by 10 MUM angiotensin (Ang) II
      in vascular smooth muscle cells (VSMCs), eleven peptides were successfully
      identified from the hydrolysate, among which His-Gly-Lys exhibited the most
      potent inhibition against [Ca(2+)]i elevation in Ang II-stimulated VSMCs
      (inhibition at 300 MUM: 46.5+/-8.0% vs. control). The biological capacity of His
      Gly-Lys analogues as an [Ca(2+)]i inhibitor was also proven when His-Lys and His
      Gly-Arg elicited a significant reduction in [Ca(2+)]i. In contrast, less
      reduction of [Ca(2+)]i by His-Gly-Ile and His-(3-methyl)-Gly-Lys indicated the
      importance of the imino proton in His, along with basic amino acids positioned at
      C-terminal for the effect.

PMID- 24444930
TI  - Effect of high hydrostatic pressure (HHP) on slowly digestible properties of rice
      starches.
AB  - The slowly digestible properties of high hydrostatic pressure (HHP)-gelatinized
      non-waxy and waxy rice starches during the retrogradation were evaluated in this
      study. The results show that slowly digestible starch (SDS) was observed at a
      higher percentage in HHP-gelatinized, non-waxy and waxy rice starches than in
      heat-gelatinized starches, after retrogradation for 7 days. The HHP treatment
      significantly reduced the enthalpy change of starch retrogradation and retarded
      the freezable water transformation into unfreezable water during retrogradation.
      This indicated that the SDS percentage was not positively correlated to the
      retrogradation degree of starch. Furthermore, X-ray diffraction (XRD) data
      revealed that the HHP treatment decreased the perfect crystallites of the 7 day
      retrograded. Non-waxy and waxy starches from 19.5% to 12.1% and 15.7% to 11.4%,
      while increased imperfect crystallites from 26.4% to 30.7% and 28.6% to 31.3%,
      respectively. These findings suggest that the higher SDS percentage can be
      attributed to the formation of less perfect crystallites and more imperfect
      crystallites during the HHP and retrogradation treatments.

PMID- 24444931
TI  - Immunoassays for trifloxystrobin analysis. Part I. Rational design of
      regioisomeric haptens and production of monoclonal antibodies.
AB  - Trifloxystrobin is one of the main active principles belonging to the strobilurin
      family of crop protection compounds. In this article, the synthesis of a battery
      of regioisomeric functionalized derivatives of trifloxystrobin is described. The
      same aliphatic linear carboxylated chain was introduced as spacer arm in all of
      the synthesized haptens, but it was located at different positions of the parent
      molecule. N,N'-Disuccinimidyl carbonate was employed for hapten activation, so
      the resulting N-hydroxysuccinimyl ester could be readily purified and efficiently
      coupled to proteins. After immunization and hybridoma generation, a collection of
      20 mouse monoclonal antibodies from different immunizing haptens was obtained.
      The analytical performance of these immunoreagents was evaluated in terms of
      affinity and selectivity with the aim to develop rapid and practical
      immunochemical procedures for trifloxystrobin determination. 

PMID- 24444932
TI  - Advanced ultra-performance liquid chromatography-photodiode array-quadrupole time
      of-flight mass spectrometric methods for simultaneous screening and
      quantification of triterpenoids in Poria cocos.
AB  - A sensitive, precise and accurate method was developed to screen and quantify
      triterpenoids based on ultra-performance liquid chromatography-photodiode array
      quadrupole time-of-flight mass spectrometry (UPLC-PDA-QTOF-MS). An exact neutral
      loss scan of 62.0004 Da (CH2O3) was used to selectively detect triterpenoids in
      Poria cocos, followed by a survey scan for exact masses of precursor and fragment
      ions of these triterpenoids. The developed method was applied to quantify seven
      major triterpenoids in 40 P. cocos samples of different origins within 18 min,
      and a total of 31 triterpenoids were unequivocally or tentatively identified.
      Principal component analysis of these samples showed a clear separation of three
      groups, and ten triterpenoids play key roles in differentiating these samples
      were obtained from the OPLS-DA variable influence on projection (VIP) plot and
      then unequivocally or tentatively identified. The developed method can be applied
      for rapid bitterness evaluation, quality control and authenticity establishment
      of P. cocos.

PMID- 24444933
TI  - Voltammetric determination of nitrite in meat products using polyvinylimidazole
      modified carbon paste electrode.
AB  - A simple and sensitive voltammetric method was developed to determine the amount
      of nitrite by using Carbon Paste Electrode (CPE) which is modified with
      polyvinylimidazole (PVI). A buffer solution of phosphate with a pH 4 value was
      used in the experiments. The amount of the nitrite-ion was determined by cyclic
      voltammetry (CV). The electro-chemical behaviour of nitrite-ion was investigated
      by using CV on the PVI modified CPE. A well-defined oxidation peak was obtained
      at 0.83 V against a reference Ag/AgCl electrode. Differential pulse voltammetry
      (DPV) was applied for the calibration plot and for the detection limit. The
      optimisation procedure was done in two steps: using a two-level factorial design
      for preliminary evaluation of the contributing factors, and the Box-Behnken
      Design (BBD) to assess the optimal experimental conditions. These are done with
      the analysis of 3 different factors in 15 runs of DPV. The optimum conditions are
      obtained within a linear response range of 5*10(-7)-1*10(-4) mol L(-1).
      Regression analysis is performed within this range showed the linear equation of
      y=0.028x+3.93*10(-7) with r(2)=0.9982, and for n=7. Limit of Detection (LOD) was
      9*10(-8) mol L(-1) with S/N=3, and Limit of Quantification (LOQ) was 3*10(-7) mol
      L(-1) with S/N=10. The procedure was used successfully to detect the amount of
      nitrite in meat products.

PMID- 24444934
TI  - In vitro evaluation method for screening of candidate prebiotic foods.
AB  - The aim of this work was to develop a simple and rapid in vitro evaluation method
      for screening and discovery of uncharacterised and untapped prebiotic foods.
      Using a NMR-based metabolomic approach coupled with multivariate statistical
      analysis, the metabolic profiles generated by intestinal microbiota after in
      vitro incubation with feces were examined. The viscous substances of Japanese
      bunching onion (JBOVS) were identified as one of the candidate prebiotic foods by
      this in vitro screening method. The JBOVS were primarily composed of sugar
      components, especially fructose-based carbohydrates. Our results suggested that
      ingestion of JBOVS contributed to lactate and acetate production by the
      intestinal microbiota, and were accompanied by an increase in the Lactobacillus
      murinus and Bacteroidetes sp. populations in the intestine and fluctuation of the
      host-microbial co-metabolic process. Therefore, our approach should be useful as
      a rapid and simple screening tool for potential prebiotic foods. 

PMID- 24444935
TI  - Antioxidant property and storage stability of quince juice phenolic compounds.
AB  - The aim of this study was to characterise, in depth, 11 quince cultivars to
      provide data for their industrial processing into high-quality juices.
      Polyphenolic composition analyses (identification and quantification), soluble
      fraction of procyanidins, antioxidant capacity assays and cluster analysis were
      measured. A total of 19 kinds of polyphenolic compounds were the following in the
      juices: before and after 6 month of storage time at 4 and 30  degrees C. Large
      variations in polyphenolic compounds content were found as affected by quince
      cultivar. The total phenolics determined by UPLC ranged from 4045 mg to 721
      mg/100 mL of juices, and was high correlated with antioxidant activity. During 6
      months of storage a significant change was observed in the content of
      polyphenols, especially in procyanidins (37% and 55%, respectively). This result
      may be useful for the juice industry as a starting point for the development of
      tasty quince juices with high levels of bioactive compounds.

PMID- 24444936
TI  - Fabrication of solid lipid microcapsules containing ascorbic acid using a
      microfluidic technique.
AB  - The importance of ascorbic acid (AA) in the human diet has motivated food
      researchers to develop AA-fortified food products. However, this compound is very
      unstable. The aim of this work was to produce solid lipid microcapsules (SLMs)
      loaded with AA using microfluidic technology. The morphology of the SLMs was
      analysed by optical, scanning electron and confocal microscopy. We determined the
      encapsulation efficiency, particle size and stability of the encapsulated
      material. Two different means of enhancing the encapsulation efficiency and
      stability of AA were demonstrated: a pore blocking method and a micromolecule
      chelating agent within the core. The results indicated the enormous potential of
      the designed vehicle to prevent AA degradation in a food product; additionally,
      this vehicle could mask the acidic taste of AA. 

PMID- 24444937
TI  - Characteristics and gel properties of gelatin from skin of seabass (Lates
      calcarifer) as influenced by extraction conditions.
AB  - Characteristics and gel properties of gelatin from seabass skin, as influenced by
      extraction conditions, were studied. Yields of gelatin extracted at 45 and 55 
      degrees C for various times were 51.6-57.3% and 62.0-66.4% (dry weight basis),
      respectively. All gelatins contained beta-chain and alpha-chains as the
      predominant components and showed a high imino acid content (198-202
      residues/1000 residues). Generally, the gel strength of gelatins decreased as the
      extraction temperature and time increased. Gelatin extracted at 45  degrees C for
      3h exhibited the highest gel strength (369 g). Gelling and melting temperatures
      for seabass skin gelatin were 19.5-20.0 and 26.3-27.0  degrees C, respectively.
      All gelatins could be set at 25  degrees C within 30 min, however gelatins
      extracted at 45  degrees C had a shorter setting time than those extracted at 55 
      degrees C (P<0.05). Gelatin from seabass skin showed a higher gel strength than
      bovine gelatin and could be used as a potential replacement for land animal
      gelatins.

PMID- 24444938
TI  - Determination of nerolidol in teas using headspace solid phase microextraction
      gas chromatography.
AB  - Nerolidol is an important volatile compound found in tea aroma, consumption of
      which has been associated with good health. A novel approach for the quantitative
      determination of nerolidol in teas has been developed using a headspace solid
      phase microextraction (HS-SPME) and a gas chromatography-flame ionization
      detector (GC-FID). The experimental parameters relating to the extraction
      efficiency of the HS-SPME such as fibre types, extraction temperature, extraction
      time, stirring rate were investigated and optimized. The study results
      demonstrated that combining GC-FID with HS-SPME was an efficient and flexible
      extraction approach for the analysis of nerolidol in teas. Using the HS-SPME-GC
      FID, the linear range of the determination of nerolidol was found to be 2.7-1360
      ng g(-1) and the limit of detection was 0.3 ng g(-1). The average recoveries were
      in the range 78.7-106% in spiked tea samples. In addition, the generation and the
      content change in nerolidol at different manufacturing stages were investigated.
      Based on the content of nerolidol in Oolong tea samples, grade judgment for the
      various teas was performed.

PMID- 24444939
TI  - Structure elucidation and immunomodulatory activity in vitro of a xylan from
      roots of Cudrania tricuspidata.
AB  - To discover new immunomodulator in the food industry, a water-soluble
      polysaccharide, CTPB1 was obtained from roots of Cudrania tricuspidata (Carr.)
      Bur. The average molecular weight of this polysaccharide was estimated to be
      4.0*10(4) Da. Monosaccharide composition analysis indicated that the only neutral
      sugar present in this polysaccharide was xylose. From methylation analysis and
      (1)H and (13)C NMR spectroscopy, the structure of CTPB1 was deduced to be (4-O
      methyl-D-glucurono)-D-xylan, with the 4-O-methyl-D-glucopyranosyluronic acid
      group linked to O-2 of a (1->4)-beta-D-xylan. The repeating unit of CTPB1 is
      composed of one non-reducing terminal residue of 4-O-methyl-D-glucuronic acid on
      every four xylose residues. Immunomodulatory activity assays in vitro showed that
      CTPB1 may induce the proliferation of mouse splenocytes. It was suggested that
      CTPB1 could be a potential immunostimulant used in the food industry.

PMID- 24444940
TI  - Molecular characterisation of waxy corn and barley starches in different solvent
      systems as revealed by MALLS.
AB  - The effect of different dissolution procedures on molecular characteristics of
      waxy starches from corn and barley were evaluated using a MALLS (batch-mode)
      detector, principally to understand the role played by different solvents.
      Starches were dissolved in aqueous solutions of: (1) 90% DMSO, (2) 2 M KOH and
      (3) 90% DMSO/2 M KOH, and stored for 15 days at ~22  degrees C with shaking.
      Weight-average molecular weight (Mw) and z-average radius of gyration (Rz) were
      determined at intervals ranging from 0 to 15 days. Regardless of starch source
      and dissolution procedures, Mw and Rz of amylopectin (AP) decreased with
      increasing storage time. Decrease in Mw followed the order: 90% DMSO>2 M KOH>90%
      DMSO/2 M KOH. However, decrease in Rz followed the order: 2 M KOH>90% DMSO/2 M
      KOH>90% DMSO. The study indicated that starch solubilisation in 90% DMSO/2 M KOH
      may be a reasonable method for molecular characterisation with less AP
      degradation.

PMID- 24444941
TI  - Phenolic compounds from Origanum vulgare and their antioxidant and antiviral
      activities.
AB  - In the present study, six new phenolic compounds (1-6) along with five known ones
      were isolated from the ethanol extract of the whole plants of Origanum vulgare.
      The structures of the new compounds were identified on the basis of extensive
      spectroscopic analyses (UV, IR, NMR, and HRESIMS) and acid hydrolysis. Twenty-one
      phenolic compounds isolated from O. vulgare in our previous and present studies
      were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1
      picryhydrazyl (DPPH) radical-scavenging and ferric-reducing antioxidant power
      (FRAP) assays; twelve of them including two new compounds exhibited significant
      antioxidant activity comparable to that of ascorbic acid. In addition, the
      antiviral effects against respiratory syncytial virus (RSV), Coxsackie virus B3
      (CVB3) and herpes simplex virus type 1 (HSV-1) were tested by cytopathic effect
      (CPE) reduction assay. 

PMID- 24444942
TI  - Amphiphilic chitosan derivative-based core-shell micelles: synthesis,
      characterisation and properties for sustained release of Vitamin D3.
AB  - Novel amphiphilic chitosan derivative of N,N-dimethylhexadecyl carboxymethyl
      chitosan (DCMCs) was synthesised. The physical properties of DCMCs were
      characterised by Fourier transform-infrared spectroscopy, nuclear magnetic
      resonance spectroscopy, X-ray diffraction and differential scanning calorimetry.
      DCMCs can form core-shell micelles with low critical micelle concentration (31 mg
      L(-1)). The core-shell micelles exhibited spherical shape with positive charge
      (+50.7 mV) and narrow size distribution (polydispersity index <0.5). Vitamin D3
      (VD3) was initially used to load into the core-shell micelles, and the solubility
      of VD3 was improved with higher encapsulation efficiency (53.2%). The in vitro
      release processes of VD3 from the core-shell micelles were initially rapid and
      then followed by a sustained release. The Higuchi model was the most suitable for
      describing the entire release procedure. DCMCs core-shell micelles are promising
      carriers for VD3 and other hydrophobic bioactive food factors.

PMID- 24444943
TI  - Effects of grown origin, genotype, harvest year, and their interactions of wheat
      kernels on near infrared spectral fingerprints for geographical traceability.
AB  - The effects of origin, genotype, harvest year, and their interactions on wheat
      near infrared (NIR) spectra were studied to find the reasons for differences in
      NIR fingerprints of wheat from different geographical origins and the stability
      of NIR fingerprints among different years. Ten varieties were grown in three
      regions of China for 2 years. 180 kernel samples were analysed by NIR. The
      spectra after pre-treatment were analysed by principal component analysis, multi
      way analysis of variance, and discriminant partial least-squares. The results
      showed that origin, genotype, year, and their interactions all had significant
      effects on wheat NIR fingerprints. The second overtones of N-H and C-H stretching
      vibrations and a combination of stretch and deformation of C-H group in wheat
      were mainly influenced by the geographical origin. The wavelength ranges 975-990
      nm, 1200 nm, and 1355-1380 nm contained plenty of origin information to build
      robust discriminant models of wheat geographical origin.

PMID- 24444944
TI  - Ellagitannin oligomers and a neolignan from pomegranate arils and their
      inhibitory effects on the formation of advanced glycation end products.
AB  - Two new ellagitannin oligomers, pomegraniins A (7, tetramer) and B (8, pentamer),
      and a new glucose ester of neolignan, pomegralignan (19), together with six known
      ellagitannins, were isolated from the arils and pericarps of Punica granatum L.
      (pomegranate). The structures of the new compounds were elucidated based on
      spectroscopic analyses and chemical evidence. The known ellagitannins included
      oligomers such as oenothein B (4), eucalbanin B (5), and eucarpanin T1 (6), in
      addition to the known ellagitannin monomers such as punicalagin (1), punicalin
      (2), and punicacortein C (3). This paper therefore represents the first report
      concerning the isolation of ellagitannin oligomers from pomegranate. Examination
      of the inhibitory activities of the polyphenolic constituents from pomegranate
      towards the formation of advanced glycation end products (AGEs) revealed that all
      ellagitannins tested were more potent inhibitors than aminoguanidine, which was
      used as a positive control, and pomegraniin A (7) showed the most potent effect. 

PMID- 24444945
TI  - Effect of packaging material on enological parameters and volatile compounds of
      dry white wine.
AB  - The enological parameters and volatile compounds of white wine packaged in dark
      coloured glass and two commercial bag-in-box (BIB) pouches (low density
      polyethylene - LDPE and ethylene vinyl acetate - EVA lined) were determined for a
      period of 6 months at 20  degrees C. Parameters monitored included: titratable
      acidity, volatile acidity, pH, total SO2, free SO2, colour, volatile compounds
      and sensory attributes. The BIB packaging materials affected the titratable
      acidity, total and free SO2 and colour of wine. A substantial portion of the wine
      aroma compounds was adsorbed by the plastic materials or lost to the environment
      through leakage of the valve fitment. Between the two plastics, the LDPE lined
      pouch showed a considerably higher aroma sorption as compared to EVA. Wine
      packaged in glass retained the largest portion of its aroma compounds. Sensory
      evaluation showed that white wine packaged in both plastics was of acceptable
      quality for 3 months vs. at least 6 months for that in glass bottles.

PMID- 24444946
TI  - Comprehensive identification of walnut polyphenols by liquid chromatography
      coupled to linear ion trap-Orbitrap mass spectrometry.
AB  - Epidemiologic studies and clinical trials have demonstrated consistent benefits
      of walnut consumption on coronary heart disease risk and other chronic diseases.
      Walnuts (Juglans regia L.) have been described previously as a rich source of
      polyphenols with a broad array of different structures. However, an accurate
      screening of its complete phenolic profile is still lacking. In the present work,
      liquid chromatography coupled with electrospray ionization hybrid linear trap
      quadrupole-Orbitrap mass spectrometry (LC-LTQ-Orbitrap) was applied for a
      comprehensive identification of phenolic compounds in walnuts. A total of 120
      compounds, including hydrolysable and condensed tannins, flavonoids and phenolic
      acids were identified or tentatively identified on the base of their retention
      times, accurate mass measurements and subsequent mass fragmentation data, or by
      comparing with reference substances and literature. The peak area of each signal
      in mass chromatograms was used to provide semiquantitative information for
      comparison purposes. The most abundant ions were observed for ellagitannins,
      ellagic acid and its derivatives. Furthermore, the high-resolution MS analysis
      revealed the presence of eight polyphenols that have never been reported in
      walnuts: stenophyllanin C, malabathrin A, eucalbanin A, cornusiin B,
      heterophylliin E, pterocarinin B, reginin A and alienanin B. 

PMID- 24444947
TI  - Effect of riboflavin on the photo-oxidative stability of vegetable oil in salad
      dressing.
AB  - Differential scanning calorimetry (DSC), headspace oxygen and solid phase
      microextraction gas chromatography and peroxide value were used to evaluate the
      effect of riboflavin on the photo-oxidation of vegetable oil in salad dressing.
      Salad dressings with 0, 5, 20, 50 and 100 ppm added riboflavin were stored under
      light (2500 lux) at 25  degrees C for 5 days. Crystallisation peaks in the DSC
      thermograms of the oil samples shifted to lower temperatures and enthalpies
      decreased as the storage time increased. As the riboflavin concentrations
      increased from 0 to 100 ppm, the crystallisation enthalpies increased from 27 to
      31 J/g and the maximum crystallisation temperature increased from -64 to -62 
      degrees C during the 5 day storage. Headspace oxygen depletion rates, the
      formation of volatile compounds and peroxide values of the salad dressing samples
      simultaneously decreased with the addition of riboflavin, showing that riboflavin
      protected the oil in salad dressing from photo-oxidation.

PMID- 24444948
TI  - Alkali- or acid-induced changes in structure, moisture absorption ability and
      deacetylating reaction of beta-chitin extracted from jumbo squid (Dosidicus
      gigas) pens.
AB  - Alkali- or acid-induced structural modifications in beta-chitin from squid
      (Dosidicus gigas, d'Orbigny, 1835) pens and their moisture absorption ability
      (MAA) and deacetylating reaction were investigated and compared with alpha-chitin
      from shrimp shells. beta-Chitin was converted into the alpha-form after 3h in 40%
      NaOH or 1-3 h in 40% HCl solution, and alpha-chitin obtained from NaOH treatment
      had higher MAA than had native alpha-chitin, due to polymorphic destructions. In
      contrast, induced alpha-chitin from acid treatment of beta-chitin had few
      polymorphic modifications, showing no significant change (P>0.05) in MAA. beta
      Chitin was more susceptible to alkali deacetylation than was alpha-chitin, and
      required a lower concentration of NaOH and shorter reaction time. These results
      demonstrate that alkali- or acid-treated beta-chitin retained high susceptibility
      toward solvents, which in turn resulted in good biological activity of beta
      chitosan for use as a natural antioxidant and antimicrobial substance or
      application as edible coatings and films for various food applications.

PMID- 24444949
TI  - A pilot study of NMR-based sensory prediction of roasted coffee bean extracts.
AB  - Nuclear magnetic resonance (NMR) spectroscopy can be considered a kind of
      "magnetic tongue" for the characterisation and prediction of the tastes of foods,
      since it provides a wealth of information in a nondestructive and nontargeted
      manner. In the present study, the chemical substances in roasted coffee bean
      extracts that could distinguish and predict the different sensations of coffee
      taste were identified by the combination of NMR-based metabolomics and human
      sensory test and the application of the multivariate projection method of
      orthogonal projection to latent structures (OPLS). In addition, the tastes of
      commercial coffee beans were successfully predicted based on their NMR metabolite
      profiles using our OPLS model, suggesting that NMR-based metabolomics accompanied
      with multiple statistical models is convenient, fast and accurate for the sensory
      evaluation of coffee. 

PMID- 24444950
TI  - Polyacetylene levels in carrot juice, effect of pH and thermal processing.
AB  - This research focuses on the study of polyacetylenes in carrot juice and their
      response to pH, storage and thermal processing conditions. Falcarindiol-3-acetate
      (FaDOAc) and falcarinol (FaOH) were in fresh carrot juice at concentrations of 73
      and 233 MUg/L, respectively. Reducing the pH of the raw carrot juice from its
      natural pH 6.13 to pH 3.5 resulted in 2 and 5 fold better extraction of FaDOAc
      and FaOH respectively in comparison to a control sample (pH 6.13). Polyacetylenes
      were retained better in acidified juices and cold storage temperatures (4 
      degrees C) for first week of storage with respect to untreated juices. An
      increase in FaDOAc and FaOH of 10- and 16-fold, respectively, as compared to raw
      unprocessed samples was observed when processing samples at 90  degrees C for 1
      min. This was assumed to be due to cell wall polysaccharides dissolution.
      However, negative correlation between total polyacetylenes and hexoses was
      confirmed by (1)H NMR spectroscopy, indicating some biological links between
      polyacetylenes and soluble sugars.

PMID- 24444951
TI  - Oxidative stabilization of mixed mayonnaises made with linseed oil and saturated
      medium-chain triglyceride oil.
AB  - Mayonnaises, made with either saturated medium chain triglyceride (MCT) oil or
      unsaturated purified linseed oil (LSO), were mixed. Raman confocal
      microspectrometry demonstrated that lipid droplets in mixed mayonnaise remained
      intact containing either MCT oil or LSO. Peroxide formation during storage was
      lower in mixed mayonnaise compared to LSO mayonnaise, while in mixed oil
      mayonnaise the level of peroxides was constantly low. Mixed oil mayonnaise had a
      lower rate of oxygen consumption than mixed mayonnaise, LSO mayonnaise having the
      highest rate. The decay of water-soluble nitroxyl radicals showed radicals are
      formed in the aqueous phase with the same rate independent of the lipids. This
      was also reflected in decay of alpha-tocopherol during storage being similar in
      MCT and LSO mayonnaises, but being stable in mixed oil mayonnaise and mixed
      mayonnaise. Results suggest that other effects than simply diluting unsaturated
      triglycerides with saturated triglycerides is causing the oxidative stabilization
      observed for mixed mayonnaise and mixed oil mayonnaise. 

PMID- 24444952
TI  - Isolation of cyanidin 3-glucoside from blue honeysuckle fruits by high-speed
      counter-current chromatography.
AB  - Blue honeysuckle fruits are rich in anthocyanins with many beneficial effects
      such as reduction of the risk of cardiovascular diseases, diabetes and cancers.
      High-speed counter-current chromatography (HSCCC) was used for the separation of
      anthocyanin on a preparative scale from blue honeysuckle fruit crude extract with
      a biphasic solvent system composed of tert-butyl methyl ether/n
      butanol/acetonitrile/water/trifluoroacetic acid (2:2:1:5:0.01, v/v) for the first
      time in this paper. Each injection of 100 mg crude extract yielded 22.8 mg of
      cyanidin 3-glucoside (C3G) at 98.1% purity. The compound was identified by means
      of electro-spray ionisation mass (ESI/MS) and (1)H and (13)C nuclear magnetic
      resonance (NMR) spectra.

PMID- 24444953
TI  - An integrated approach utilising chemometrics and GC/MS for classification of
      chamomile flowers, essential oils and commercial products.
AB  - As part of an ongoing research program on authentication, safety and biological
      evaluation of phytochemicals and dietary supplements, an in-depth chemical
      investigation of different types of chamomile was performed. A collection of
      chamomile samples including authenticated plants, commercial products and
      essential oils was analysed by GC/MS. Twenty-seven authenticated plant samples
      representing three types of chamomile, viz. German chamomile, Roman chamomile and
      Juhua were analysed. This set of data was employed to construct a sample class
      prediction (SCP) model based on stepwise reduction of data dimensionality
      followed by principle component analysis (PCA) and partial least squares
      discriminant analysis (PLS-DA). The model was cross-validated with samples
      including authenticated plants and commercial products. The model demonstrated
      100.0% accuracy for both recognition and prediction abilities. In addition, 35
      commercial products and 11 essential oils purported to contain chamomile were
      subsequently predicted by the validated PLS-DA model. Furthermore, tentative
      identification of the marker compounds correlated with different types of
      chamomile was explored. 

PMID- 24444954
TI  - Sorption of 4-ethylguaiacol and 4-ethylphenol on yeast cell walls, using a
      synthetic wine.
AB  - 4-Ethylphenol (4-EP) and 4-ethylguaiacol (4-EG) are the identified volatile
      phenolic compounds associated with off-odour in wine. The aim of this work was to
      investigate the kinetics and thermodynamics of sorption of 4-EG and 4-EP by yeast
      cell walls, using a synthetic wine. Results showed that the sorption capacity by
      yeast cell walls for 4-EG was greater than that for 4-EP and that the kinetics of
      4-EG were quicker, although the unions were weaker than in the case of 4-EP. The
      retention of these compounds was by means of specific chemical sorption. The
      process of sorption of these compounds to the yeast walls could be due to their
      binding to the residual lipids, as well as to interaction of 4-EP and 4-EG
      (positively charged compounds), with the functional groups of the mannoproteins
      and the free amino acids of the surface of the cell walls. 

PMID- 24444955
TI  - Maximising the phytochemical content and antioxidant activity of Ecuadorian brown
      rice sprouts through optimal germination conditions.
AB  - Germinated brown rice (GBR) is considered a healthy alternative to white rice in
      the fight against chronic diseases. As the functional quality of GBR depends on
      genotype and germination conditions, the objectives were to identify suitable
      Ecuadorian brown rice cultivars and optimal germination time and temperature to
      maximise gamma-aminobutyric acid (GABA), total phenolics compounds (TPC) and
      antioxidant activity of GBR. Regression models for the prediction of
      phytochemical composition and antioxidant activity in GBR were also obtained.
      Germination improved GABA, TPC and antioxidant activity in all cultivars. Maximum
      GABA and antioxidant activity were attained at 34  degrees C for 96 h, while the
      highest TPC was found at 28  degrees C for 96 h in all cultivars. GBR cv. GO
      displayed the highest antioxidant activity and cv. 15 was the most effective at
      accumulating GABA and TPC in the optimal germination conditions. Therefore,
      Ecuadorian GBR could be used for the preparation of functional foods serving as
      preventative strategies in combating chronic diseases.

PMID- 24444956
TI  - A novel formulation of thiamine dilaurylsulphate and its preservative effect on
      apple juice and sterilised milk.
AB  - Thiamine dilaurylsulphate (TLS), synthesised by a new method, was developed for a
      formulation with a wide antimicrobial spectrum and evaluated in apple juice and
      milk. The result of a disc diffusion method showed that TLS, which was
      synthesised from sodium lauryl sulphate and thiamine hydrochloride, had strong
      growth-inhibitory effects on Gram-positive bacteria, yeasts, and moulds, but had
      weak inhibitory effects on Gram-negative bacteria such as Escherichia coli.
      Moreover, the TLS antibacterial spectrum could be broadened to all microbes by
      formulation with organic acids, such as gluconic acid or acetic acid, since
      organic acids have synergistic effects on TLS bacteriostasis. Compared to TLS,
      the formulation had a better preservation in milk (pH 6.64) by viable microbial
      counting, although the antibacterial effect of the formulation with TLS showed no
      significant difference in apple juice (pH 3.98). Therefore, the TLS formulation
      has wide application and better potential, as a preservative, to enhance food
      safety. 

PMID- 24444957
TI  - Peptides in pepsin-pancreatin hydrolysates from commercially available soy
      products that inhibit lipopolysaccharide-induced inflammation in macrophages.
AB  - The potential of pepsin-pancreatin hydrolysates, from different foods, to inhibit
      inflammation using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages as an
      in vitro model was evaluated. Eight different products were digested sequentially
      with pepsin and pancreatin and were evaluated for their anti-inflammatory
      properties. Hydrolysates from strawberry-banana soymilk (SBH), mixed berry
      soymilk (MXH) and vanilla soymilk (SVMH) inhibited the production of nitric oxide
      (27.9%, 16.4% and 28.6%, respectively), interleukin-1beta (26.3%, 39.5% and
      21.6%, respectively) and tumour necrosis factor-alpha (50.2%, 47.5% and 33.3%,
      respectively). In addition, SBH, MXH and SVMH inhibited the expression of pro
      inflammatory enzymes: inducible nitric oxide synthase (66.7%, 65.1% and 88.0%,
      respectively) and cyclooxygenase-2 (62.0%, 69.9% and 40.6%, respectively).
      Bioactive peptides (RQRK and VIK) were generated. In conclusion, soymilk products
      can potentially be used to maintain health under inflammatory stress. 

PMID- 24444958
TI  - Characteristics of the starch fine structure and pasting properties of waxy rice
      during storage.
AB  - Two waxy rice (TNW1 and TCSW1, exhibiting high and low amylase activity,
      respectively), were stored at 4 and 17  degrees C (polished rice) and at room
      temperature (paddy rice) for 15 months. The fine structure of starch isolated
      from the aged rice and the pasting properties of starch and rice flour were
      studied. After storage, the percentage of short amylopectin (AP) chains increased
      in TNW1, and no uniform changing pattern was observed in the chain-length (CL)
      distribution of TCSW1. The viscosity of starch isolated from the aged rice
      increased as the storage temperature and duration increased. We hypothesised that
      this increase was due to the hydrolysis of AP by endogenous amylase and the
      generation of small clusters during storage, which caused the simple dissociation
      of AP and a high swelling degree of starch granules during gelatinisation. Factor
      analysis of the first two factors associated with the characteristics of
      viscograms and the CL of AP explained 72% of the total variation.

PMID- 24444959
TI  - The relationship between growth stages and aroma composition of lemon basil
      Ocimum citriodorum Vis.
AB  - Volatiles from infusions of lemon basil Ocimum citriodorum Vis were evaluated by
      SPME-GC/MS. Citral, linalool and estragole were the major constituents. Citral,
      the major contributor to the lemony flavour, was significantly higher in post
      flowering (79%) and full-flowering (65%), it was reduced to 42% at pre-flowering.
      Linalool was consistent throughout the growth cycle (2-3%). Estragole was higher
      in pre-flowering representing 15% of the total volatiles present. Linalool levels
      dropped sharply during the full-flowering and post-flowering stages to 2% and
      0.4%, respectively. Volatiles from different parts of lemon basil were evaluated
      to determine the parts that influence the flavour. The percentage composition of
      citral for leaves and flowers was 64.5% and 58% for the branches. Linalool was
      much higher in flowers (13%), followed by 11% in branches and 3% in leaves. The
      flavour attributes of lemon basil infusions can be improved by incorporating
      aerial branches and flowers in the tea. 

PMID- 24444960
TI  - A comparative study of physicochemical characteristics and functionalities of
      pinto bean protein isolate (PBPI) against the soybean protein isolate (SPI) after
      the extraction optimisation.
AB  - Optimisation of protein extraction yield from pinto bean was investigated using
      response surface methodology. The maximum protein yield of 54.8 mg/g was obtained
      with the optimal conditions of: temperature=25  degrees C, time=1 h and buffer-to
      sample ratio=20 ml/g. PBPI was found to obtain high amount of essential amino
      acids such as leucine, lysine, and phenylalanine compared to SPI. The predominant
      proteins of PBPI were vicilin and phytohemagglutinins whereas the predominant
      proteins of SPI were glycinin and conglycinins. Significantly higher emulsifying
      capacity was found in PBPI (84.8%) compared to SPI (61.9%). Different isoelectric
      points were found in both PBPI (4.0-5.5) and SPI (4.0-5.0). Also, it was found
      that PBPI obtained a much higher denaturation temperature of 110.2  degrees C
      compared to SPI (92.5  degrees C). Other properties such as structural
      information, gelling capacity, water- and oil-holding capacities, emulsion
      stability as well as digestibility were also reported.

PMID- 24444961
TI  - Dose-dependent response of nitrogen stable isotope ratio to proportion of legumes
      in diet to authenticate lamb meat produced from legume-rich diets.
AB  - This study investigated the dose-dependent response in lamb meat of stable
      nitrogen isotope ratio to the dietary proportion of legumes, and the ability of
      the nitrogen isotope signature of the meat to authenticate meat produced from
      legume-rich diets. Four groups of nine male Romane lambs grazing a cocksfoot
      pasture were supplemented with different levels of fresh alfalfa forage to obtain
      four dietary proportions of alfalfa (0%, 25%, 50% and 75%) for 98 days on average
      before slaughter (groups L0, L25, L50 and L75). We measured the stable nitrogen
      isotope ratio in the forages and in the longissimus thoracis muscle. The
      delta(15)N value of the meat decreased linearly with the dietary proportion of
      alfalfa. The distribution of the delta(15)N values of the meat discriminated all
      the L0 lambs from the L75 lambs, and gave a correct classification score of 85.3%
      comparing lambs that ate alfalfa with those that did not.

PMID- 24444962
TI  - In vitro antioxidant activity of extracts from common legumes.
AB  - The in vitro antioxidant activity of pinto bean, cowpea, baby lima bean, lentil,
      chickpea, small red bean, red kidney bean, black kidney bean, navy bean, and mung
      bean extracts were investigated. Significant differences were observed in the
      phenolic content and the antioxidant activity amongst the legume extracts.
      Lentils demonstrated the highest phenolic content (47.6 mg/g), total antioxidant
      activity (720.68 U/g), DPPH* scavenging activity (38.5%), and total reducing
      power, whereas baby lima beans and navy beans had the lowest. Amongst the
      extracts, hydroxyl radicals (*OH) scavenging was higher in black kidney bean
      (85.68%) and baby lima bean (74.97%) extracts. The total antioxidant activity
      (r=0.84), DPPH* scavenging activity (r=0.83), and total reducing power (r=0.84)
      were positively correlated with the total phenolic content. However, *OH
      scavenging and the phenolic content were not correlated.

PMID- 24444963
TI  - Effect of viticulture practices on concentration of polyphenolic compounds and
      total antioxidant capacity of Southern Italy red wines.
AB  - This study aims to assess the effect of three wine grape varieties, three
      training systems and two bud loads on the Total Antioxidant Capacity (TAC) and
      polyphenolic composition of Southern Italy red wines produced, during two
      vintages. Overall, Primitivo, Malvasia nera of Brindisi-Lecce and Montepulciano
      as grape varieties, single Guyot (SG), single spur pruned low cordon (SLC) and
      single spur pruned high wire cordon (HSLC) as training systems, 8 and 12
      buds/plant as bud loads were compared. Significant differences in the
      polyphenolic families were shown by the grape varieties and by modifying the vine
      growing practices. Moreover, the results demonstrated that varieties influenced
      the TAC (indicating the Malvasia as the more effective one), that SLC led to the
      lowest level of TAC and that 8 buds/plant increased it. The relationship between
      antioxidant indexes and the concentration of single polyphenolic families was
      evaluated and the highest correlation was found between the total polyphenols and
      the proanthocyanidins family. 

PMID- 24444964
TI  - A role for anthocyanin in determining wine tannin concentration in Shiraz.
AB  - Four wines were made to investigate the effect of different anthocyanin and
      tannin fruit concentrations on wine phenolics and colour. Wines that were made
      from fruit with high anthocyanin concentration had high tannin concentrations
      regardless of the concentration of tannin in fruit, while wines made from fruit
      with low anthocyanin also had low tannin concentration. It was found that fruit
      anthocyanin concentration correlated with wine tannin concentration, wine colour
      and polymeric pigment formation. Anthocyanin concentration might be a key
      component for increasing tannin solubility and extraction into wine and the
      formation of polymeric pigments. Industry implications include managing tannin
      and anthocyanin fruit concentration for targeting tannin extraction and polymeric
      pigment formation in wine. 

PMID- 24444965
TI  - Wheat bran particle size influence on phytochemical extractability and
      antioxidant properties.
AB  - It is unknown if particle size plays a role in extracting health promoting
      compounds in wheat bran because the extraction of antioxidant and phenolic
      compounds with particle size reduction has not been well documented. In this
      study, unmilled whole bran (coarse treatment) was compared to whole bran milled
      to medium and fine treatments from the same wheat bran. Antioxidant properties
      (capacity, ability, power), carotenoids and phenolic compounds (phenolic acids,
      flavonoids, anthocyanins) were measured and compared. The ability of whole bran
      fractions of differing particle size distributions to inhibit free radicals was
      assessed using four in vitro models, namely, diphenylpicrylhydrazyl radical
      scavenging activity, ferric reducing/antioxidant power (FRAP) assay, oxygen
      radical absorbance capacity (ORAC), and total antioxidant capacity. Significant
      differences in phytochemical concentrations and antioxidant properties were
      observed between whole bran fractions of reduced particle size distribution for
      some assays. The coarse treatment exhibited significantly higher antioxidant
      properties compared to the fine treatment; except for the ORAC value, in which
      coarse was significantly lower. For soluble and bound extractions, the coarse
      treatment was comparatively higher in total antioxidant capacity (426.72 mg
      ascorbic acid eq./g) and FRAP value (53.04 MUmol FeSO4/g) than bran milled to the
      finer treatment (314.55 ascorbic acid eq./g and 40.84 MUmol FeSO4/g,
      respectively). Likewise, the fine treatment was higher in phenolic acid (7.36 mg
      FAE/g), flavonoid (206.74 MUg catechin/g), anthocyanin (63.0 MUg/g), and
      carotenoid contents (beta carotene, 14.25 MUg/100 g; zeaxanthin, 35.21 MUg/100 g;
      lutein 174.59 MUg/100 g) as compared to the coarse treatment. An increase of
      surface area to mass increased the ORAC value by over 80%. With reduction in
      particle size, there was a significant increase in extracted anthocyanins,
      carotenoids and ORAC value. Particle size does effect the extraction of
      phytochemicals.

PMID- 24444966
TI  - Composition, structure, morphology and physicochemical properties of lablab bean,
      navy bean, rice bean, tepary bean and velvet bean starches.
AB  - The composition, morphology, structure and physicochemical properties of starches
      from lablab bean, navy bean, rice bean, tepary bean and velvet bean were
      examined. Starch yield (on a whole seed basis), total lipid, apparent amylose
      (AM) and starch damage were in the range 20.6-29.9%, 0.48-0.62%, 22.1-32.1% and
      0.004-0.011%, respectively. Difference in amylopectin chain length distribution
      amongst the starches was marginal. The starches differed significantly with
      respect to granule morphology, molecular order, molecular orientation, double
      helical content, gelatinization parameters, swelling factor, AM leaching, thermal
      stability and enzyme hydrolysis. The results showed that interplay amongst
      differences in molecular order, double helical content, relative crystallinity,
      AM content, granule morphology and the extent of interaction between and amongst
      starch chains within the amorphous and crystalline domains, influenced thermal,
      rheological and digestibility properties. 

PMID- 24444967
TI  - Physicochemical parameters and sensory properties of honeys from Buenos Aires
      region.
AB  - The physicochemical parameters (moisture, hydroxymethyl furfural, colour,
      electrical conductivity, free acidity, glucose, fructose and sucrose) and the
      sensory properties(aroma, taste, appeareance, texture) were determined in honeys
      from apiaries of the agricultural, hills and meadow zones of the south east
      region of Buenos Aires province (Argentina). The analysis of variance showed
      significant differences among zones in the mean value of hydroximethyl furfural,
      colour, electrical conductivity and sucrose content. The principal component
      analysis explained the 70% of the variance among samples with the first two
      principal components in both cases. The cluster analysis and linear discriminant
      analysis showed that samples were grouped in relation to the sampling region
      coinciding with the results of the principal component analysis. Results suggest
      that could be possible to classify honeys according to the geographic origin
      based on the physicochemical parameters; however, the sensory properties were not
      good predictors. 

PMID- 24444968
TI  - Determination of some physicochemical characteristics, bioactive compounds and
      antioxidant activity of tropical fruits from Yucatan, Mexico.
AB  - The aim to the study was to determine the physicochemical composition, bioactive
      compounds and antioxidant activity of fruits from Yucatan, Mexico such as star
      apple, cashew, mombin, mamey sapote, white sapote, sugar apple, sapodilla, dragon
      fruit, nance, ilama, custard apple, mamoncillo and black sapote. The
      physicochemical characteristics were different between fruits and were good
      sources of bioactive compounds. The edible part with the highest values of
      antioxidant activity were mamoncillo, star apple, mombin, cashew, white sapote,
      ilama, custard apple, sugar apple, and nance. Total soluble phenols content
      showed a correlation with antioxidant activity by ABTS (R=0.52, P?0.05) and DPPH
      (R=0.43, P?0.05). A high correlation was obtained between the two assays (ABTS
      and DPPH) used to measure antioxidant activity in the tropical fruit species
      under study (R=0.82, P?0.05). The results show promising perspectives for the
      exploitation and use of tropical fruits studied with significant levels of
      nutrients and antioxidant activity. 

PMID- 24444969
TI  - Vaccinium corymbosum L. (blueberry) extracts exhibit protective action against
      cadmium toxicity in Saccharomyces cerevisiae cells.
AB  - Blueberries (Vaccinium corymbosum L.) are a rich source of antioxidants and their
      consumption is believed to contribute to food-related protection against
      oxidative stress. In the present study, the chemoprotective action of blueberry
      extracts against cadmium toxicity was investigated using a cadmium-hypersensitive
      strain of Saccharomyces cerevisiae. Four varieties of blueberries were used in
      the study, and it was found that the extracts with high content of total
      anthocyanidins exhibited significant protective effect against the toxicity of
      cadmium and H2O2. Both the blueberry extracts and pure cyanidin exhibited
      protective effects against cadmium in a dose-dependent manner, but without
      significantly interfering with the cadmium accumulation by the yeast cells. The
      results imply that the blueberry extracts might be a potentially valuable food
      supplement for individuals exposed to high cadmium. 

PMID- 24444970
TI  - The phenolic chemistry and spectrochemistry of red sweet wine-making and oak
      aging.
AB  - A natural sweet wine (NSW) was made with dried grapes from Vitis vinifera L. cv
      Garnacha Tintorera. A fortified sweet wine (FSW) was also obtained: the
      maceration-alcoholic fermentation of Garnacha Tintorera must was stopped by
      addition of ethanol 96% (v/v). UV/Vis spectrophotometry and HPLC/DAD-ESI/MS were
      applied to determine, respectively, the evolution of colour and phenolic
      compounds in Garnacha Tintorera based-sweet wines during aging. In sweet wines,
      aging decreased a(*) (red/green), colour saturation and lightness and increased
      b(*) (yellow/blue), and hue angle. Most of the phenolic compounds determined,
      such as anthocyanins, esters of hydroxycinnamic acids, flavan-3-ols monomers,
      oligomers and polymers decreased in both sweet wines during aging. On the
      contrary, hydroxybenzoic and hydroxycinnamic acids and vitisins increased after
      one year of aging. Despite that both terminal and extension subunit compositions
      show very small changes, mean degree of polymerisation of proanthocyanidins
      decline slightly as aging progressed in both sweet wines. 

PMID- 24444971
TI  - Chemical composition and antioxidant and anti-inflammatory potential of peels and
      flesh from 10 different pear varieties (Pyrus spp.).
AB  - This study was performed to compare the contents of total phenolics, total
      flavonoids, and total triterpenes between peel and flesh of ten different pear
      cultivars. The monomeric compounds were analyzed by HPLC, their antioxidant and
      anti-inflammatory activities were also measured. Peel and flesh from Yaguang,
      Hongpi, Qingpi and Guifei varieties contained relatively more total phenolic,
      total flavonoids and total triterpene, and showed stronger antioxidant and anti
      inflammatory activities, while Lvbaoshi and Youran appeared to be weakest among
      them. All the chemical components found in the pear peel were approximately 6-20
      times higher than those in the flesh of pear. For the monomeric compounds,
      arbutin, oleanolic acid, ursolic acid, chlorogenic acid, epicatechin, and rutin
      were the dominant components contained in the ten pear cultivars both in peel and
      in flesh. All of the analyses suggested that the peel of pear might be an
      excellent polyphenol and triterpenes source. 

PMID- 24444972
TI  - 8-C N-ethyl-2-pyrrolidinone substituted flavan-3-ols as the marker compounds of
      Chinese dark teas formed in the post-fermentation process provide significant
      antioxidative activity.
AB  - Phytochemical investigation of the aqueous extract of pu-erh tea afforded eight
      novel 8-C N-ethyl-2-pyrrolidinone substituted flavan-3-ols (puerins I-VIII) by
      (1)H, (13)C, two-dimensional nuclear magnetic resonance (NMR) and high
      performance liquid chromatography with diode array detection and electrospray
      ionization mass spectrometry (HPLC-DAD-ESI/MS) analysis. Comparative chemical
      analysis of green tea, black tea and Chinese dark teas confirmed that these
      compounds were the marker compounds of Chinese dark teas. Furthermore, fungal
      fermentation was indispensable for the biosynthesis of these novel compounds.
      Through single fungal fermentation, it was proved that catechins and theanine
      were the precursors of puerins I-VIII. HPLC-DAD-ESI/MS analysis elucidated the
      biosynthetic pathway for puerins I-VIII. Puerins I-IV have potential protective
      effects for the human micro-vascular endothelial cells (HMEC) injury induced by
      hydrogen dioxide compared to other tea polyphenols. 8-C N-ethyl-2-pyrrolidinone
      substituted flavan-3-ols could be used in the quality control and authentication
      of Chinese dark teas.

PMID- 24444973
TI  - Effects of season and plantation on phenolic content of unfermented and fermented
      Sri Lankan tea.
AB  - The effects of season and plantation on the polyphenol content of Camellia
      sinensis (tea) leaves were determined. Aqueous and organic extracts of freeze
      dried fresh (unfermented) and black (fully-fermented) tea leaves were prepared
      for a structured set of samples (fermented and unfermented teas from six high-,
      mid- and low-grown plantations; fermented and unfermented teas from two
      harvesting seasons from four highland plantations), collected from the main tea
      growing regions in Sri Lanka. Total catechin content and amounts of individual
      catechins, flavonols and theaflavins were determined by HPLC. Mean values for the
      phenolic constituents were generally significantly higher (p<0.05) with solvent
      extraction. The mean values for total catechins, total flavonols and caffeine in
      the aqueous extracts from unfermented teas were 10.6%, 1.5% and 2.9%,
      respectively. For both unfermented and fermented tea leaves, a significant
      (p<0.05) interaction between plantation and season was observed for phenolic
      constituents. Ferric reducing antioxidant power was positively (p<0.05)
      correlated with (-)-epicatechin gallate and total phenolic contents. 

PMID- 24444974
TI  - Preparation of antioxidants from sugarcane molasses.
AB  - Supercritical carbon dioxide fluid extraction with piecewise distillation
      separation was used to obtain antioxidants from sugarcane molasses. Extraction
      pressure, time, temperature, flow rate of CO2 and ethanol content were selected
      as the independent variables. Oxygen radical absorbance capacity was used to
      evaluate the antioxidant activity of the extract. Results showed that conditions
      to obtain the highest total oxygen radical absorbance capacity value of sugarcane
      molasses extract were determined to be an extraction pressure of 33.3 MPa,
      temperature of 43.3  degrees C, time of 86.7 min, 90% ethanol content of
      sugarcane molasses and flow rate of CO2 of 20 L/h. Under the conditions stated
      above, the experimental value was 2584.9. This study indicated that supercritical
      carbon dioxide fluid extraction with piecewise distillation separation can
      effectively extract antioxidants from sugarcane molasses.

PMID- 24444975
TI  - Interactions between grape skin cell wall material and commercial enological
      tannins. Practical implications.
AB  - Commercial enological tannins were used to investigate the role that cell wall
      material plays in proanthocyanidin adsorption. Insoluble cell wall material,
      prepared from the skin of Vitis vinifera L. cv. Monastrell berries, was combined
      with solutions containing six different commercial enological tannins
      (proanthocyanidin-type tannins). Analysis of the proanthocyanidins in the
      solution, after fining with cell wall material, using phloroglucinolysis and size
      exclusion chromatography, provided quantitative and qualitative information on
      the non-adsorbed compounds. Cell wall material showed strong affinity for the
      proanthocyanidins, one of the commercial tannins being bound up to 61% in the
      experiment. Comparison of the molecular mass distribution of the commercial
      enological tannins in solution, before and after fining, suggested that cell
      walls affinity for proanthocyanidins was more related with the proanthocyanidin
      molecular mass than with their percentage of galloylation. These interactions may
      have some enological implications, especially as regards the time of commercial
      tannins addition to the must/wine. 

PMID- 24444976
TI  - Characterization of the bacteriocin BacJ1 and its effectiveness for the
      inactivation of Salmonella typhimurium during turkey escalope storage.
AB  - During a screening programme for bacteriocin producers, a new lactic acid
      bacterium called J1, isolated from chicken gizzard, was noted to produce a
      bacteriocin (BacJ1) that inhibited Gram-positive and Gram-negative food-borne
      pathogens, especially Salmonella typhimurium, and it was, therefore, selected for
      identification and further study. The results, from 16S rRNA gene nucleotide
      sequencing (1583 pb accession no HE861352) and phylogenetic analysis, suggested
      that the new isolate be assigned as Weissella paramesenteroides J1. BacJ1 was
      purified from the culture supernatant of the J1 strain using heat treatment (15
      min at 90  degrees C), 80% ammonium sulfate precipitation, and gel filtration
      (Sephadex G25). MALDI-TOF analyses revealed that BacJ1 had an exact molecular
      mass of 1881.036 Da. The analysis of the N-terminal sequence (GPAGPFGKLY) of this
      active peptide revealed no significant similarity to currently available
      antimicrobial peptides. The addition of pre-purified BacJ1, at a final
      concentration of 400 AU per gramme, may open new promising opportunities for the
      prevention of contamination from and growth of pathogenic bacteria, particularly
      S. typhimurium, during turkey escalope storage at 4  degrees C.

PMID- 24444977
TI  - Evaluation of apple juice quality using spectral fluorescence signatures.
AB  - In current work the method of in vivo evaluation of apple juice degree of
      naturalness based on Spectral Fluorescence Signature (SFS) is proposed. SFS
      spectra of intact apple juice were measured as excitation-emission matrix by
      specially designed compact spectrofluorimeter with front-face optical layout -
      Instant Screener Compact (LDI AS, Estonia). The data were analysed using PCA
      method with a view to evaluate the information of polyphenol's content in
      different commercial juices. Results of PCA analysis have shown a clear
      separation of juice reconstituted from concentrate, unclarified pasteurised juice
      and personally squeezed apple juice at the two dimensional PCs space. For
      implementation of apple juice analysis into spectrofluorimeter software the k
      Nearest Neighbor (kNN) Search technique was used. The implemented model was
      tested using 19 different samples of apple juice. Results of test demonstrate
      that SFS-PCA-kNN method can provide quick nondestructive analysis of naturalness
      degree of commercial apple juice. 

PMID- 24444978
TI  - Towards an improved prediction of the free radical scavenging potency of
      flavonoids: the significance of double PCET mechanisms.
AB  - The 1H(+)/1e(-) and 2H(+)/2e(-) proton-coupled electron transfer (PCET) processes
      of free radical scavenging by flavonoids were theoretically studied for aqueous
      and lipid environments using the PM6 and PM7 methods. The results reported here
      indicate that the significant contribution of the second PCET mechanism,
      resulting in the formation of a quinone/quinone methide, effectively
      discriminates the active from inactive flavonoids. The predictive potency of
      descriptors related to the energetics of second PCET mechanisms (the second O-H
      bond dissociation enthalpy (BDE2) related to hydrogen atom transfer (HAT)
      mechanism, and the second electron transfer enthalpy (ETE2) related to sequential
      proton loss electron transfer (SPLET) mechanism) are superior to the currently
      used indices, which are related to the first 1H(+)/1e(-) processes, and could
      serve as primary descriptors in development of the QSAR (quantitative structure
      activity relationships) of flavonoids. 

PMID- 24444979
TI  - Determination of technological maturity of grapes and total phenolic compounds of
      grape skins in red and white cultivars during ripening by near infrared
      hyperspectral image: a preliminary approach.
AB  - Hyperspectral images of intact grapes during ripening were recorded using a near
      infrared hyperspectral imaging system (900-1700 nm). Spectral data have been
      correlated with grape skin total phenolic concentration, sugar concentration,
      titratable acidity and pH by modified partial least squares regression (MPLS)
      using a number of spectral pre-treatments and different sets of calibration. The
      obtained results (RSQ and SEP, respectively) for the global model of red and
      white grape samples were: 0.89 and 1.23 mg g(-1) of grape skin for total phenolic
      concentration, 0.99 and 1.37  degrees Brix for sugar concentration, 0.98 and 3.88
      g L(-1) for titratable acidity and for pH 0.94 and 0.12. Moreover, separate
      calibration models for red and white grape samples were also developed. The
      obtained results present a good potential for a fast and reasonably inexpensive
      screening of these parameters in intact grapes and therefore, for a fast control
      of technological and phenolic maturity.

PMID- 24444980
TI  - Antioxidative effect of purple corn extracts during storage of mayonnaise.
AB  - Anthocyanin is a powerful natural antioxidant. Purple corn husk is rich in
      anthocyanin. In this paper the antioxidative effect of anthocyanin-rich purple
      corn husk extract (PCHE) in mayonnaise during storage was studied. The
      antioxidative effect of the mayonnaise containing PCHE was evaluated by measuring
      peroxide values, p-anisidine values, total oxidation values, acid values, and
      iodine values at time intervals for 10 weeks. The antioxidative effect of the
      mayonnaise containing PCHE was higher than that of mayonnaise with chemical
      antioxidants BHT and EDTA as positive control. The mayonnaise containing 0.4 g/kg
      PCHE showed the strongest antioxidative performance during storage. This study
      suggests that PCHE could be used as natural antioxidant in high fat food and as a
      substitute to chemical antioxidant with its purplish colour marking its
      difference from ordinary mayonnaise. Such colour difference will tell consumers
      that their food contains natural antioxidants.

PMID- 24444981
TI  - Effect of ultra high pressure homogenization treatment on the bioactive compounds
      of soya milk.
AB  - Ultra high pressure homogenization (UHPH) is a useful novel technology to obtain
      safe and high-quality liquid foods. The effect of UHPH at 200 and 300 MPa in
      combination with different inlet temperatures (Tin) (55, 65 and 75  degrees C) on
      the bioactive compounds of soya milk was studied. Total phytosterols increased
      with the higher combination of pressure and temperature. The main phytosterol was
      beta-sitosterol, followed by stigmasterol and campesterol. Total tocopherols in
      UHPH-treated soya milks decreased as the temperature and pressure increased. UHPH
      treatment also affected the different chemical forms of tocopherols. No biogenic
      amines were detected in any of the analyzed soya milks. Meanwhile, the polyamines
      SPD and SPM were found in all soya milks, being stable to the UHPH treatment.
      Total isoflavones increased with the higher combination of pressure and
      temperature. No differences in the isoflavone profile were found, with beta
      glucoside conjugates being the predominant form.

PMID- 24444982
TI  - Changes in macrominerals, trace elements and pigments content during lettuce
      (Lactuca sativa L.) growth: influence of soil composition.
AB  - Changes in macrominerals, trace elements and photosynthetic pigments were
      monitored at 5 stages of lettuce growth. Plants were grown in three experimental
      agriculture greenhouse fields (A1, A2 and A3). Soil composition was also
      monitored to understand its influence on lettuce composition. In general, the
      content of macrominerals, trace elements, chlorophylls and carotenoids decreased
      during lettuce growth and consequently, high nutritional value was observed at
      younger stages. A2 lettuces showed an increase of Fe, Al, Cr, V and Pb due to the
      different soil physicochemical parameters. Multiple linear regression analysis
      with stepwise variable selection, indicated that soil characteristics, namely,
      pH(CaCl2) for Fe and Cr, silt and fine-sand for Al and V, OM for Al and Pb,
      coarse-sand and CEC for Cr, had a key role determining element bioavailability
      and plant mineral content. Thus, lettuce nutritional value was strongly dependent
      of growth stage and soil characteristics. 

PMID- 24444983
TI  - Quantification of polycyclic aromatic hydrocarbons in toasted guarana (Paullinia
      cupana) by high-performance liquid chromatography with a fluorescence detector.
AB  - Samples of toasted guarana seeds with husk from Maues (Amazonia) and ten samples
      of different brands of guarana powder produced in different parts of Brazil were
      analysed in this work, aiming to identify and quantify 16 PAHs. The samples were
      analysed by high-performance liquid chromatography equipped with fluorescence and
      UV-Vis detectors. Naphthalene was identified and quantified in the guarana
      samples (0.13 and 0.78 MUg kg(-1)) and both naphthalene and phenanthrene were
      found in two commercial guarana powder samples (0.36-1.54 and 0.03-0.06 MUg kg(
      1), respectively). Considering that the average daily intake of guarana powder is
      equivalent to 10 g, it can be seen that guarana powder contains less PAHs than
      the limit established in European legislation for other kinds of food (CE
      835/2011), that is, around 0.20 MUg kg(-1) of PAHs.

PMID- 24444984
TI  - Determination of the mineral composition of Caigua (Cyclanthera pedata) and
      evaluation using multivariate analysis.
AB  - Caigua (in Brazil "maxixe do reino") is a fruit that is generally consumed either
      cooked or even raw as salad. This fruit has been used as a food and also in folk
      medicine. In this work, the mineral composition of Caigua was determined for the
      first time. Twenty-nine samples from five farms located in the southwestern
      region of Bahia, Brazil were acquired and analyzed using inductively coupled
      plasma optical emission spectrometry. The elements determined in this fruit
      included calcium, magnesium, sodium, potassium, phosphorus, manganese, iron,
      zinc, copper and vanadium. Principal component analysis (PCA) and hierarchical
      cluster analysis (HCA) were applied to evaluate the obtained results. The average
      concentrations of the determined elements (expressed as mg 100 g(-1)) were as
      follows: 0.91 for sodium, 152 for potassium, 19.4 for phosphorus, 11.9 for
      calcium, 8.4 for magnesium, 0.074 for manganese, 0.21 for iron, 0.013 for copper,
      0.13 for zinc and 0.015 for vanadium.

PMID- 24444985
TI  - Chemical and sensory profiles of makgeolli, Korean commercial rice wine, from
      descriptive, chemical, and volatile compound analyses.
AB  - The chemical and sensory profiles of 12 commercial samples of makgeolli, a Korean
      rice wine, were determined using descriptive sensory, chemical, and volatile
      components analyses. The sample wines were analysed for their titratable acidity,
      ethanol content, pH, Hunter colour value and total reducing sugars. The chemical
      compositions of the makgeolli samples were found to be significantly different.
      The volatile compounds were extracted with solid-phase microextraction and
      analysed by gas chromatography time-of-flight mass spectrometry. In all, 45 major
      volatile compounds, consisting of 33 esters, 8 alcohols, 1 aldehyde, 1 acid, 1
      phenol and 1 terpene, were identified; each makgeolli sample included 28-35
      volatile compounds. Based on principal component analysis of the sensory data,
      samples RW1, RW2, RW5, RW8 and RW12 were associated with roasted cereal, mouldy,
      bubbles, sweet and sour attributes; the other samples were associated with
      sensory attributes of yellowness, yeast, full body, turbidity, continuation,
      swallow, alcohol, fruit aroma and whiteness. 

PMID- 24444986
TI  - Lingual nerve neuropraxia following use of the Laryngeal Mask Airway Supreme.
AB  - Cranial nerve injury is a rare complication with the use of supraglottic airway
      devices. A case of lingual nerve injury following the use of a Laryngeal Mask
      Airway Supreme in a 45 year old woman is presented. A review of the literature
      regarding lingual nerve injury as a complication of the supraglottic airway is
      also presented. 

PMID- 24444987
TI  - Malpositioning of peripherally inserted central catheters is less frequent when
      the left arm is used.

PMID- 24444988
TI  - The effects of a small-dose ketamine-propofol combination on tourniquet-induced
      ischemia-reperfusion injury during arthroscopic knee surgery.
AB  - STUDY OBJECTIVE: To determine the effects of a small-dose ketamine-propofol
      combination used for sedation during spinal anesthesia on tourniquet-induced
      ischemia-reperfusion injury. STUDY DESIGN: Prospective randomized study. SETTING:
      Training and research hospital. PATIENTS: 60 adult, ASA physical status 1 and 2
      patients, ages 20-60 years, scheduled for elective arthroscopic knee surgery for
      meniscal and chondral lesions. INTERVENTIONS: The initial hemodynamic parameters
      were recorded and blood samples were collected at baseline (T1); then spinal
      anesthesia was performed. In Group I (n=30), a combination of 0.5 mg/kg/hr of
      ketamine and 2 mg/kg/hr of propofol was administered; Group II (n=30) received an
      equivalent volume of saline as an infusion. A pneumatic tourniquet was applied.
      MEASUREMENTS: Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase
      levels were measured one minute before tournique deflation in the ischemic period
      (T2), then 5 (T3) and 30 (T4) minutes following tourniquet deflation in the
      reperfusion period. MAIN RESULTS: No differences were noted between groups in
      hemodynamic data (P > 0.05) or SOD levels (P > 0.05). In Group I, MDA levels at
      T2 were lower than in Group II (P < 0.05). In Group I, catalase levels were lower
      at T2 and T4 than they were in Group II (P < 0.05). CONCLUSION: Small-dose
      ketamine-propofol combination may be useful in reducing tourniquet-induced
      ischemia-reperfusion injury in arthroscopic knee surgery.

PMID- 24444989
TI  - A neck burn of unexpected etiology during magnetic resonance imaging of a one
      year old boy.

PMID- 24444990
TI  - Nepalese patients' anxiety and concerns before surgery, by Pokharel et al. Reply.

PMID- 24444991
TI  - Total systemic ropivacaine concentrations following aerosolized intraperitoneal
      delivery using the AeroSurge.
AB  - STUDY OBJECTIVE: To evaluate intraperitoneal ropivacaine delivery with the
      AeroSurge device in the clinical setting and to evaluate the total systemic
      ropivacaine levels achieved following delivery of 50 mg of aerosolized
      ropivacaine. DESIGN: Preliminary, prospective, nonrandomized study. SETTING:
      Operating room of a university hospital. PATIENTS: 5 consecutive ASA physical
      status 1 and 2 patients undergoing elective laparoscopic Nissen fundoplication or
      cholecystectomy. INTERVENTION: Five mL of 1% ropivacaine was delivered through
      the 10 mm port using the AeroSurge device at peritoneal insufflation.
      MEASUREMENTS: Venous blood samples were collected and total ropivacaine
      concentration was determined using liquid chromatography-mass spectrometry. MAIN
      RESULTS: The AeroSurge device delivered ropivacaine, visible as mist within the
      peritoneal cavity. Peak concentration (Cmax) was attained between 10 and 30
      minutes following the end of aerosolized ropivacaine delivery. At no stage did
      any level approach toxic levels. CONCLUSIONS: This preliminary study confirms
      that aerosolized intraperitoneal local anesthetic is feasible, with ropivacaine
      concentrations remaining within safe levels.

PMID- 24444992
TI  - Inconsistency between simultaneous blood pressure measurements in the arm,
      forearm, and leg in anesthetized children.
AB  - STUDY OBJECTIVE: To determine the accuracy and precision of simultaneous
      noninvasive blood pressure (NIBP) measurement in the arm, forearm, and ankle in
      anesthetized children. DESIGN: Prospective, randomized study. SETTING: University
      medical center. PATIENTS: 101 ASA physical status 1 and 2 children (aged 1-8 yrs)
      scheduled for elective surgery with general anesthesia. MEASUREMENTS:
      Simultaneous NIBP measurements were recorded at the arm, forearm, and ankle at 5
      minute intervals. MAIN RESULTS: The systolic blood pressure difference between
      the arm-forearm or the arm-ankle was within the +/- 10% range in 63% and 29% of
      measurements, and within the +/- 20% range in 85% and 67% of measurements,
      respectively. The diastolic blood pressure difference between the arm-forearm or
      the arm-ankle was within the +/- 10% range in 42% and 44% and within the +/- 20%
      range in 67% and 74% of measurements, respectively. In patients in whom the
      initial three NIBP measurements were within the +/- 20% range between the forearm
      and arm, 86% of the subsequent measurements were also within that limit.
      CONCLUSIONS: Forearm and ankle NIBP measurements are unreliable and inconsistent
      with NIBP measured in the arm of anesthetized children. These alternative BP
      measurement sites are not reliable in accuracy (comparison with reference "gold"
      standard) and precision (reproducibility).

PMID- 24444993
TI  - Intraoperative cardiac arrest: was it the ACE inhibitor?
AB  - Continuing renin-angiotensin-aldosterone system antagonist therapy on the day of
      surgery is controversial, and appears to contribute to intraoperative
      hypotension. A patient presenting for cerebral aneurysm clipping continued her
      angiotensin-converting enzyme inhibitor on the morning of surgery, and
      subsequently experienced significant postinduction hypotension that culminated in
      cardiac arrest. Following successful resuscitation, she returned 6 weeks later to
      have her aneurysm clipped using identical anesthetic management; her blood
      pressure medications were held on the day of surgery. 

PMID- 24444994
TI  - Re: Nepalese patients' anxiety and concerns before surgery, by Pokharel et al.

PMID- 24444995
TI  - Kinesthesia in a sustained-attention driving task.
AB  - This study investigated the effects of kinesthetic stimuli on brain activities
      during a sustained-attention task in an immersive driving simulator. Tonic and
      phasic brain responses on multiple timescales were analyzed using time-frequency
      analysis of electroencephalographic (EEG) sources identified by independent
      component analysis (ICA). Sorting EEG spectra with respect to reaction times (RT)
      to randomly introduced lane-departure events revealed distinct effects of
      kinesthetic stimuli on the brain under different performance levels. Experimental
      results indicated that EEG spectral dynamics highly correlated with performance
      lapses when driving involved kinesthetic feedback. Furthermore, in the realistic
      environment involving both visual and kinesthetic feedback, a transitive
      relationship of power spectra between optimal-, suboptimal-, and poor-performance
      groups was found predominately across most of the independent components. In
      contrast to the static environment with visual input only, kinesthetic feedback
      reduced theta-power augmentation in the central and frontal components when
      preparing for action and error monitoring, while strengthening alpha suppression
      in the central component while steering the wheel. In terms of behavior, subjects
      tended to have a short response time to process unexpected events with the
      assistance of kinesthesia, yet only when their performance was optimal. Decrease
      in attentional demand, facilitated by kinesthetic feedback, eventually
      significantly increased the reaction time in the suboptimal-performance state.
      Neurophysiological evidence of mutual relationships between behavioral
      performance and neurocognition in complex task paradigms and experimental
      environments, presented in this study, might elucidate our understanding of
      distributed brain dynamics, supporting natural human cognition and complex
      coordinated, multi-joint naturalistic behavior, and lead to improved
      understanding of brain-behavior relations in operating environments. 

PMID- 24444997
TI  - Thermostable sites and catalytic characterization of xylanase XYNB of Aspergillus
      niger SCTCC 400264.
AB  - In order to improve the expression of heat-resistant xylanase XYNB from
      Aspergillus niger SCTCC 400264, XynB has been cloned into Pichia pastoris
      secretary vector pPIC9K. The XynB production of recombinant P. pastoris was four
      times as E. coli, the Vmax and specific activity of XynB reached 2,547.7 MUmol/mg
      and 4,757 U/mg, respectively. And the XynB still had 74% residual enzyme activity
      after 30 min-heat treatment at 80 degrees C. The van der Waals force analysis in
      XYNB (ACN89393 and AAS67299), there is one more oxygen radicals in AAS67299 in
      their catalytic site, indicating that the local cavity is much more free, and it
      is more optimal for substrate binding, affinity reaction, and proton transfer
      etc, and eventually increasing enzyme activity. The H-bonds analysis of XYNB
      indicated that there are two more H-bonds in 33rd Ser of XYNB (AAS67299) than
      33rd Ala(ACN89393 ), two H-bonds between Ser70 and Asp67.

PMID- 24444998
TI  - Genome sequence and comparative genome analysis of Pseudomonas syringae pv.
      syringae type strain ATCC 19310.
AB  - Pseudomonas syringae pv. syringae (Psy) is a major bacterial pathogen of many
      economically important plant species. Despite the severity of its impact, the
      genome sequence of the type strain has not been reported. Here, we present the
      draft genome sequence of Psy ATCC 19310. Comparative genomic analysis revealed
      that Psy ATCC 19310 is closely related to Psy B728a. However, only a few type III
      effectors, which are key virulence factors, are shared by the two strains,
      indicating the possibility of host-pathogen specificity and genome dynamics, even
      under the pathovar level.

PMID- 24444996
TI  - BNST neurocircuitry in humans.
AB  - Anxiety and addiction disorders are two of the most common mental disorders in
      the United States, and are typically chronic, disabling, and comorbid. Emerging
      evidence suggests the bed nucleus of the stria terminalis (BNST) mediates both
      anxiety and addiction through connections with other brain regions, including the
      amygdala and nucleus accumbens. Although BNST structural connections have been
      identified in rodents and a limited number of structural connections have been
      verified in non-human primates, BNST connections have yet to be described in
      humans. Neuroimaging is a powerful tool for identifying structural and functional
      circuits in vivo. In this study, we examined BNST structural and functional
      connectivity in a large sample of humans. The BNST showed structural and
      functional connections with multiple subcortical regions, including limbic,
      thalamic, and basal ganglia structures, confirming structural findings in
      rodents. We describe two novel connections in the human brain that have not been
      previously reported in rodents or non-human primates, including a structural
      connection with the temporal pole, and a functional connection with the
      paracingulate gyrus. The findings of this study provide a map of the BNST's
      structural and functional connectivity across the brain in healthy humans. In
      large part, the BNST neurocircuitry in humans is similar to the findings from
      rodents and non-human primates; however, several connections are unique to
      humans. Future explorations of BNST neurocircuitry in anxiety and addiction
      disorders have the potential to reveal novel mechanisms underlying these
      disabling psychiatric illnesses. 

PMID- 24444999
TI  - Construction and characterization of an enhanced GFP-tagged TIM-1 fusion protein.
AB  - TIM-1 (also known as KIM-1 and HAVcr-1) is a type I transmembrane glycoprotein
      member of the TIM family that may play important roles in innate and adaptive
      immune responses. The overexpression of proteins associated with membrane
      proteins is a major obstacle to overcome in studies of membrane protein
      structures and functions. In this study, we successfully coupled the
      overexpression of the TIM-1 protein with a C-terminal enhanced green fluorescent
      protein (GFP) tag in Escherichia coli. To the best of our knowledge, this report
      is the first to describe the overexpression of human TIM-1 in E. coli. The
      purified TIM-1-EGFP fusion protein recognized and bound directly to apoptotic
      cells and did not to bind to viable cells. Furthermore, we confirmed that the
      interactions of TIM-1-EGFP with apoptotic cells were blocked by TIM-1-Fc fusion
      proteins. This fusion protein represents a readily obtainable source of
      biologically active TIM-1 that may prove useful in future studies of human TIM-1.

PMID- 24445000
TI  - Gendered experiences of sexual abuse of teenagers and children in Mexico.
AB  - The prevalence of sexual abuse during childhood and adolescence in a national
      representative sample of Mexican youngsters is examined from a gender perspective
      using data from the 2007 National Survey on Exclusion, Intolerance and Violence
      in Public Institutions of High School Level Education. Of those surveyed, 1.76%
      were forced into their first experience of intercourse, and 6.43% had their
      genitalia touched or their first sexual interaction imposed against their will.
      In this sample, 6.82% had experienced sexual abuse before the age of 18. Child
      sexual abuse was most commonly perpetrated by family members and neighbors. Only
      20% reported being abused by an unknown person. Males and females had different
      victimization experiences. Forty percent disclosed information about the abuse to
      another person, and 7% reported their experiences to law enforcement agencies.
      Males and females stated different reasons for not disclosing. These findings are
      discussed within the context of the social construction of the male and female
      body and sexuality in the Mexican context. 

PMID- 24445001
TI  - Lessons learned from leadership.

PMID- 24445002
TI  - Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery
      of lercanidipine hydrochloride.
AB  - Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of
      hypertension. It is a poor water soluble drug with absolute bioavailability of
      10%. The aim of this study was to design lercanidipine hydrochloride-loaded
      nanostructured lipid carriers to investigate whether the bioavailability of the
      same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured
      lipid carriers were prepared by the method of solvent evaporation at a high
      temperature and solidification by freeze drying. The nanostructured lipid
      carriers were evaluated for particle size analysis, zeta potential, entrapment
      efficiency, in vitro drug diffusion, ex vivo permeation studies and
      pharmacodynamic study. The resultant nanostructured lipid carriers had a mean
      size of 214.97 nm and a zeta potential of -31.6 +/- 1.5 mV. More than 70%
      lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated
      the formation of type 2 nanostructured lipid carriers. The in vitro release
      studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the
      drug entrapped in the nanostructured lipid carriers remains entrapped at acidic
      pH. The ex vivo studies indicated that the drug release was enhanced from 10% to
      60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs
      released lercanidipine hydrochloride in a controlled manner for a prolonged
      period of time as compared to plain drug. These results clearly indicate that
      nanostructured lipid carriers are a potential controlled release formulation for
      lercanidipine hydrochloride and may be a promising drug delivery system for the
      treatment of hypertension.

PMID- 24445003
TI  - Ageing and moisture uptake in polymethyl methacrylate (PMMA) bone cements.
AB  - Bone cements are extensively employed in orthopaedics for joint arthroplasty,
      however implant failure in the form of aseptic loosening is known to occur after
      long-term use. The exact mechanism causing this is not well understood, however
      it is thought to arise from a combination of fatigue and chemical degradation
      resulting from the hostile in vivo environment. In this study, two commercial
      bone cements were aged in an isotonic fluid at physiological temperatures and
      changes in moisture uptake, microstructure and mechanical and fatigue properties
      were studied. Initial penetration of water into the cement followed Fickian
      diffusion and was thought to be caused by vacancies created by leaching monomer.
      An increase in weight of approximately 2% was experienced after 30 days ageing
      and was accompanied by hydrolysis of poly(methyl methacrylate) (PMMA) in the
      outermost layers of the cement. This molecular change and the plasticising effect
      of water resulted in reduced mechanical and fatigue properties over time. Cement
      ageing is therefore thought to be a key contributor in the long-term failure of
      cemented joint replacements. The results from this study have highlighted the
      need to develop cements capable of withstanding long-term degradation and for
      more accurate test methods, which fully account for physiological ageing. 

PMID- 24445004
TI  - Structure-mechanical function relations at nano-scale in heat-affected human
      dental tissue.
AB  - The knowledge of the mechanical properties of dental materials related to their
      hierarchical structure is essential for understanding and predicting the effect
      of microstructural alterations on the performance of dental tissues in the
      context of forensic and archaeological investigation as well as laser irradiation
      treatment of caries. So far, few studies have focused on the nano-scale structure
      mechanical function relations of human teeth altered by chemical or thermal
      treatment. The response of dental tissues to thermal treatment is thought to be
      strongly affected by the mineral crystallite size, their spatial arrangement and
      preferred orientation. In this study, synchrotron-based small and wide angle X
      ray scattering (SAXS/WAXS) techniques were used to investigate the micro
      structural alterations (mean crystalline thickness, crystal perfection and degree
      of alignment) of heat-affected dentine and enamel in human dental teeth.
      Additionally, nanoindentation mapping was applied to detect the spatial and
      temperature-dependent nano-mechanical properties variation. The SAXS/WAXS results
      revealed that the mean crystalline thickness distribution in dentine was more
      uniform compared with that in enamel. Although in general the mean crystalline
      thickness increased both in dentine and enamel as the temperature increased, the
      local structural variations gradually reduced. Meanwhile, the hardness and
      reduced modulus in enamel decreased as the temperature increased, while for
      dentine, the tendency reversed at high temperature. The analysis of the
      correlation between the ultrastructure and mechanical properties coupled with the
      effect of temperature demonstrates the effect of mean thickness and orientation
      on the local variation of mechanical property. This structural-mechanical
      property alteration is likely to be due to changes of HAp crystallites, thus
      dentine and enamel exhibit different responses at different temperatures. Our
      results enable an improved understanding of the mechanical properties correlation
      in hierarchical biological materials, and human dental tissue in particular. 

PMID- 24445005
TI  - beta-TCP-polylactide composite scaffolds with high strength and enhanced
      permeability prepared by a modified salt leaching method.
AB  - A modified particulate leaching method for fabrication of strong calcium
      phosphate-polymer composite scaffolds with improved pore interconnectivity is
      reported. The scaffolds were produced by mixing precompacted composite granules
      (beta-TCP with 40vol% PLA) of different size and density with salt particles
      followed by high pressure consolidation (at room temperature or 120 degrees C)
      and porogen dissolution. The scaffolds' compressive strength and Darcy's
      permeability were found to be inversely related and to be strongly dependent on
      the processing parameters. The use of precompacted granules instead of the loose
      beta-TCP-PLA powder allowed us to increase permeability by three orders of
      magnitude while maintaining load bearing characteristics. Scaffolds with 50%
      porosity prepared from large (300-420MUm) composite granules of beta-TCP-40vol%
      PLA and salt porogen particles of comparable size exhibited the best combination
      of compressive strength (4-6MPa) and permeability (1.3-1.6*10(-10)m(2)) falling
      within the range of trabecular bone. 

PMID- 24445006
TI  - A bone remodelling model including the effect of damage on the steering of BMUs.
AB  - Bone remodelling in cortical bone is performed by the so-called basic
      multicellular units (BMUs), which produce osteons after completing the
      remodelling sequence. Burger et al. (2003) hypothesized that BMUs follow the
      direction of the prevalent local stress in the bone. More recently, Martin (2007)
      has shown that BMUs must be somehow guided by microstructural damage as well. The
      interaction of both variables, strain and damage, in the guidance of BMUs has
      been incorporated into a bone remodelling model for cortical bone. This model
      accounts for variations in porosity, anisotropy and damage level. The bone
      remodelling model has been applied to a finite element model of the diaphysis of
      a human femur. The trajectories of the BMUs have been analysed throughout the
      diaphysis and compared with the orientation of osteons measured experimentally.
      Some interesting observations, like the typical fan arrangement of osteons near
      the periosteum, can be explained with the proposed remodelling model. Moreover,
      the efficiency of BMUs in damage repairing has been shown to be greater if BMUs
      are guided by damage. 

PMID- 24445007
TI  - Incidence, risk factor, and prognosis of end-stage renal disease after heart
      transplantation in Chinese recipients.
AB  - BACKGROUND/PURPOSE: End-stage renal disease (ESRD) is an important complication
      arising after heart transplantation. At least 3-10% of recipients reach ESRD
      within 10 years after transplant. The incidence of ESRD in Chinese recipients has
      not been reported. Here we sought to assess the incidence, prognosis, and risk
      factors for ESRD in Chinese recipients. METHODS: We conducted a retrospective
      analysis of 248 heart recipients who survived >1 year from 1998 through 2007.
      ESRD was defined as the requirement of maintenance dialysis. RESULTS: Renal
      dysfunction was present in 20 patients (8%) prior to transplant. With a follow-up
      duration of 5.8 +/- 3.9 years, 30 patients developed ESRD. The cumulative
      incidence of ESRD after heart transplantation was 2.1% +/- 0.9%, 6.5% +/- 1.8%,
      16.8% +/- 3.3%, and 36.5% +/- 9.5% at 2, 5, 10, and 15 years after transplant,
      respectively. Median onset of ESRD was 6.9 years after transplant. Actuarial
      survival after dialysis was 74.8% +/- 8.3%, 66.6% +/- 9.2%, and 43.6% +/- 12.6%
      at 1, 2, and 5 years, respectively. Independent risk factors for ESRD included
      pretransplant serum creatinine (hazard ratio, 1.84; p = 0.001), presence of
      diabetes prior to transplant (hazard ratio, 2.51; p = 0.017), and old age at
      transplant (hazard ratio, 1.05; p = 0.008). CONCLUSION: There was a high
      incidence of ESRD in Chinese heart recipients. Patients with ESRD had poor
      prognosis after dialysis.

PMID- 24445008
TI  - Decreased expression of zonula occludens-1 and occludin in the bladder urothelium
      of patients with interstitial cystitis/painful bladder syndrome.
AB  - BACKGROUND/PURPOSE: Unique barrier properties of the urothelial surface membrane
      permit urine storage without contents leak into the bloodstream. Previous reports
      suggested that the bladder urothelial barrier might be compromised in
      interstitial cystitis/painful bladder syndrome (IC/PBS). We examined the changes
      of tight junction proteins (zonula occludens-1 (ZO-1) and occludin) in IC/PBS
      patients. METHODS: Bladder samples were derived from of 32 patients with IC/PBS
      and eight controls. We detected the tight junction proteins of ZO-1 and occludin
      expression by immunoblotting, immunohistochemical (IHC) staining and double
      immunofluorescent (IF) staining with confocal microscopy. Data were analyzed
      using the Mann-Whitney U-test. RESULTS: Expression of ZO-1 and occludin in the
      IC/PBS group was reduced compared to the control group by immunoblotting and IHC
      staining. Also, the thinning and denudation of urothelium were demonstrated in
      the IC/PBS group by histological study. IF staining showed the interruption of
      bladder urothelium in IC/PBS patients under confocal microscopy. CONCLUSION: Our
      data showed that decreased expression of tight junction proteins (ZO-1 and
      occludin) and interruption of bladder urothelium in IC/PBS patients. Treatment to
      repair the discontinuous urothelium may be useful to relieve some clinical
      symptoms of patients with IC/PBS.

PMID- 24445009
TI  - Comparison of domiciliary oxygen using liquid oxygen and concentrator in northern
      Taiwan.
AB  - BACKGROUND/PURPOSE: Long-term oxygen therapy has become standard treatment for
      patients with chronic respiratory insufficiency. However, patterns of long-term
      home oxygen therapy have not been well studied in Taiwan. Oxygen concentrator
      systems are commonly used in Taiwan, but liquid oxygen delivery systems are
      portable and may provide advantages over the concentrator system. This study
      compared oxygen usage between patients from a liquid oxygen group (LOG) and an
      oxygen concentrator group (OCG). The authors also assessed the physiologic
      responses of patients with chronic obstructive pulmonary disease (COPD) to
      ambulatory oxygen use at home. METHODS: The study used a retrospective, cross
      sectional, observational survey design. The LOG comprised 42 patients, and the
      OCG comprised 102 patients. We recruited participants in northern Taiwan from
      July 2009 to April 2010. The questionnaire instruments that were used to collect
      data consisted of three parts: demographic characteristics, devices used in
      respiratory care, and activity status with portable oxygen. Two-minute walking
      tests were performed on COPD patients in their homes. RESULTS: COPD was the most
      common diagnosis in our study, with more than 50% of patients who received oxygen
      long term in both groups having received this diagnosis. The LOG used oxygen for
      an average of 21.7 hours per day, whereas OCG averaged 15.2 hours per day
      (p<0.001). In the OCG, 92.2% of patients used a concentrator alone, whereas 23.8%
      of the LOG used liquid oxygen alone (p<0.001). The LOG patients were involved in
      significantly more outdoors activities (p=0.002) and reported traveling with
      oxygen more often (p<0.001) than the OCG patients. For patients with the same
      dyspnea level of COPD severity, those using liquid oxygen had a lower increase in
      pulse rate after the walking test, in comparison with the concentrator users.
      CONCLUSION: Patients in the LOG used oxygen for longer hours, went on more
      outings, and were more likely to travel with oxygen than patients in the OCG.
      Being ambulatory with liquid oxygen might enable patients with COPD to walk more
      effectively.

PMID- 24445010
TI  - Multiphoton microscopy imaging of developing tooth germs.
AB  - BACKGROUND/PURPOSE: Traditionally, tooth germ is observed by histological
      investigation with hematoxylin and eosin stain and information may loss during
      the process. The purpose of this study is to use multiphoton laser fluorescence
      microscopy to observe the developing tooth germs of mice for building up the
      database of the images of tooth germs and compare with those from conventional
      histological analysis. METHODS: Tooth germs were isolated from embryonic and
      newborn mice with age of Embryonic Day 14.5 and Postnatal Days 1, 3, 5, and 7.
      RESULTS: Comparison of the images of tooth germ sections in multiphoton
      microscopy with the images of histology was performed for investigating the molar
      tooth germs. It was found that various signals arose from different structures of
      tooth germs. Pre-dentin and dentin have strong second-harmonic generation
      signals, while ameloblasts and enamel tissues were shown with strong
      autofluorescence signals. CONCLUSION: In this study, a novel multiphoton
      microscopy database of images from developing tooth germs in mice was set up. We
      confirmed that multiphoton laser microscopy is a powerful tool for investigating
      the development of tooth germ and is worthy for further application in the study
      of tooth regeneration.

PMID- 24445011
TI  - Epigallocatechin-3-gallate inhibits lysophosphatidic acid-stimulated connective
      tissue growth factor via JNK and Smad3 suppression in human gingival fibroblasts.
AB  - BACKGROUND/PURPOSE: Connective tissue growth factor (CTGF/CCN2) is involved in
      the development and progression of fibrotic diseases, including gingival
      overgrowth (GO). Recent studies indicate that lysophosphatidic acid (LPA) is also
      significantly involved in wound healing and the development of fibrosis. This
      study investigated whether epigallocatechin-3-gallate (EGCG) can inhibit LPA
      induced CCN2 expression in human gingival fibroblast (GF) and its mechanism.
      METHODS: Western blot analyses were used to study the signaling pathways of LPA
      induced CCN2 expression in human GFs and the effects of EGCG on this pathway.
      RESULTS: LPA stimulated CCN2 synthesis in human GFs. This effect can be
      significantly inhibited bytransforming growth factor-beta type I receptor/ALK5,
      Smad3, and JNK inhibitors but not ERK, P38, and MAPK inhibitors. EGCG completely
      inhibited LPA-induced CCN2 expression through attenuating the LPA-induced JNK and
      Smad3 phosphorylation in human GFs. CONCLUSION: LPA produced at the surgical
      wound may contribute to the recurrence of GO by upregulating CCN2 expression in
      human GFs. This effect was mediated by Smad3 and JNK activation and ALK5
      transactivation. EGCG could be a useful agent for reducing the recurrence of GO
      after surgery through suppression of JNK and Smad3 activations.

PMID- 24445012
TI  - Misdiagnosed desmoplastic small round cell tumor of the pleura: case report and
      literature review.

PMID- 24445013
TI  - Dairy products on metabolic health: current research and clinical implications.
AB  - Dairy products have been thought to have a beneficial role in the metabolic
      syndrome (MetS). MetS constitutes a cluster of risk factors for an increased
      mortality, including obesity, impaired glucose homeostasis, hypertension and
      atherogenic dyslipidemia. Individuals with MetS are also often in a chronic, low
      grade inflammatory state. The objective of this review is to examine recent meta
      analyses and clinical studies on the association between dairy products
      consumption and these MetS risk factors. Findings from studies demonstrate that
      weight loss related to dairy product intake is due to the combination of an
      energy-restricted diet with consumption of dairy products. Further, a limited
      number of studies have shown beneficial effects of dairy consumption on plasma
      lipids, blood pressure, glucose homeostasis or inflammatory and oxidative stress
      profiles. Overall, this review article suggests that adults should consume at
      least 2-3 servings of dairy products per day within a well-balanced diet and a
      healthy lifestyle for metabolic health. Yet, higher dairy product consumption may
      have additional beneficial effects, but more well-designed intervention studies
      are needed to ascertain these effects. 

PMID- 24445014
TI  - CCL28 involvement in mucosal tissues protection as a chemokine and as an
      antibacterial peptide.
AB  - CCL28 chemokine is expressed by epithelial cells of various mucosal tissues. This
      chemokine binds to CCR3 and CCR10 receptors and plays an essential role in the
      IgA antibody secreting cells (IgA-ASC) homing to mucosal surfaces and to
      lactating mammary gland as well. In addition, CCL28 has been shown to exert a
      potent antimicrobial activity against both Gram-negative and Gram-positive
      bacteria and fungi. Using the pig model, we investigated the expression of both
      CCR10 and CCR3 receptors in a large panel of mucosal tissues. RT-PCR analysis
      revealed the expression of CCR3 and CCR10 mRNA in salivary glands, nasal mucosae,
      Peyer's patches, small and large intestine, suggesting the presence of leucocytes
      expressing these receptors within these tissues. CCR10 mRNA was observed in sow
      mammary gland at late gestation with an increasing level during lactation.
      Recombinant porcine CCL28 protein was produced and mass spectrometry analysis
      revealed antimicrobial chemokines features such as a high pI value (10.2) and a C
      terminal highly positively-charged region. Using a viable count assay, we showed
      that CCL28 displayed antimicrobial activity against enteric pathogens and was
      effective in killing Salmonella serotypes Dublin and Choleraesuis, enteroinvasive
      Escherichia coli K88 and non-pathogenic E. Coli K12. The potent antimicrobial
      function of CCL28 combined with its wide distribution in mucosal tissues and
      secretions suggest that this protein plays an important role in innate immune
      protection of the epithelial surfaces.

PMID- 24445015
TI  - Predictors of response to Infliximab in children with luminal Crohn's disease.
AB  - OBJECTIVE: A significant proportion of patients with initial response to
      Inflximab (IFX), subsequently lose response (LOR). Multicentre paediatric studies
      report LOR in 33% to 50% with 3-5year follow-up. Our retrospective study examined
      durability of response and predictors of LOR. METHODS: From our IBD database of
      185 children with CD, 65 received IFX maintenance therapy for luminal or
      fistulising Crohn's disease between January, 2006 and April, 2013. 47 with
      luminal CD >=1year follow-up after commencing IFX were included. We evaluated
      variables associated with response and describe outcomes on those remaining on
      IFX at four time points; before IFX, after induction, at 1year and at the last
      follow-up. Response was divided into sustained primary, recovered, durable
      (combined sustained primary and recovered) and complete LOR (discontinuation from
      LOR or intolerance). RESULTS: Overall, 28/47 (60%) children sustained primary
      response over a median duration of 2.83years (1.6-4.4, IQR). 19/47 (40%)
      developed LOR (including 2 intolerant) at a median of 11months (9-19, IQR). Of 17
      with LOR, 7 were successfully re-induced giving durable response (35/47, 74%); 6
      failed dose intensification needing surgery (n=2), second anti-TNF (n=2) or both
      (n=2). 4 had surgery without dose intensification. LOR was associated with low
      BMI at diagnosis, lower height Z scores prior to induction, elevated CRP
      following induction (p=0.007) and failure to use concomitant IM (p=0.02).
      CONCLUSION: The cumulative probability of durable response to IFX in luminal CD
      was 83%, 74% and 70% after 1, 2, and 3years on IFX maintenance therapy.

PMID- 24445016
TI  - Gender and hemispheric differences in temporal lobe epilepsy: a VBM study.
AB  - PURPOSE: Gender differences are recognized in the functional and anatomical
      organization of the human brain. Differences between genders are probably
      expressed early in life, when differential rates of cerebral maturation occur.
      Sexual dimorphism has been described in temporal lobe epilepsy with mesial
      temporal sclerosis (TLE-MTS). Several voxel-based morphometry (VBM) studies have
      shown that TLE-MTS extends beyond mesial temporal structures, and that there are
      differences in the extent of anatomical damage between hemispheres, although none
      have approached gender differences. Our aim was to investigate gender differences
      and anatomical abnormalities in TLE-MTS. METHODS: VBM5 was employed to analyze
      gender and hemispheric differences in 120 patients with TLE-MTS and 50 controls.
      RESULTS: VBM abnormalities were more widespread in left-TLE; while in women
      changes were mostly seen in temporal areas, frontal regions were more affected in
      men. CONCLUSIONS: Our study confirmed that gender and laterality are important
      factors determining the nature and severity of brain damage in TLE-MTS.
      Differential rates of maturation between gender and hemispheres may explain the
      distinct areas of anatomical damage in men and women.

PMID- 24445017
TI  - Primary school teacher's knowledge and attitudes toward children with epilepsy.
AB  - PURPOSE: Primary school teacher's knowledge and attitudes toward epilepsy can
      have significant impact on the performance and psycho-social development of the
      child with epilepsy. Our objectives were to study teacher's knowledge and
      attitudes and identify areas in which further teacher training and education are
      required. METHODS: A stratified random sample survey involving a group of primary
      school teachers in Jeddah, Saudi Arabia included private/public schools
      designated for male and female students. A structured 37-item questionnaire was
      used to examine their demographics, knowledge, attitudes, and experience with
      epilepsy. RESULTS: Six hundred and twenty primary school teachers working in
      public (58%) or private (42%) schools were included with ages ranging between 21
      and 59 years (mean 36). Most teachers (79%) were of Saudi Arabian nationality and
      66% had a college or university degree. Their years of experience ranged from 1
      to 35 (mean 13.5). Only 17% of the teachers felt very well informed about
      epilepsy. Teachers with higher education were more likely to have good knowledge
      (p=0.009). Teachers of Saudi nationality were also more likely to report good
      knowledge, independent of their educational level (p=0.013). Overall, teachers
      with good knowledge were less likely to have negative attitudes including minding
      to have an epileptic child in their class (p=0.028) or thinking that they should
      be placed in a special classroom (p=0.029). CONCLUSIONS: Primary school teacher's
      knowledge about epilepsy needs improvements. Their attitudes correlated highly
      with their knowledge. Educational campaigns about epilepsy are needed to develop
      a well informed and tolerant community.

PMID- 24445018
TI  - Combining morphometrics with molecular taxonomy: how different are similar
      foliose keratose sponges from the Australian tropics?
AB  - Sponge taxonomy can be challenging as many groups exhibit extreme morphological
      plasticity induced by local environmental conditions. Foliose keratose sponges of
      the sub-family Phyllospongiinae (Dictyoceratida, Thorectidae: Strepsichordaia,
      Phyllospongia and Carteriospongia) are commonly found in intertidal and subtidal
      habitats of the Indo-Pacific. Lacking spicules, these sponges can be difficult to
      differentiate due to the lack of reliable morphological characters for species
      delineation. We use molecular phylogenies inferred from the nuclear Internal
      Transcribed Spacer 2 region (ITS2) and morphometrics (19 characters; 52 character
      states) to identify evolutionarily significant units (ESUs; sensu Moritz) within
      foliose Phyllosponginiids collected from seven geographic locations across
      tropical eastern and Western Australia. The ITS2 topology was congruent with the
      tree derived from Bayesian inference of discrete morphological characters
      supporting expected taxonomic relationships at the genus level and the
      identification of five ESUs. However, phylogenies inferred from the ITS2 marker
      revealed multiple sequence clusters, some of which were characterised by distinct
      morphological features and specific geographic ranges. Our results are discussed
      in light of taxonomic incongruences within this study, hidden sponge diversity
      and the role of vicariant events in influencing present day distribution
      patterns. 

PMID- 24445019
TI  - Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in
      diabetic rats via suppression of Rho-kinase pathway.
AB  - Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of
      iatrogenic, drug-induced acute renal failure. This study aimed to investigate the
      protective effects of atorvastatin against renal tubular cell apoptosis in
      diabetic rats and the related mechanisms. CI-AKI was induced by intravenous
      administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats.
      Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and
      30mg/kg/d in different groups, respectively, for 5 days before iopromide
      injection. Renal function parameters, kidney histology, renal tubular cell
      apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho
      associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin
      phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown
      to notably ameliorate contrast medium induced medullary damage, restore renal
      function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up
      regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase
      3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation
      of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose
      dependently ameliorate the development of CI-AKI, which was partly attributed to
      its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK
      pathway. 

PMID- 24445020
TI  - Twin delivery: method, timing and conduct.
AB  - The incidence of twin pregnancy has increased worldwide over the past 10 years,
      largely as a consequence of the assisted reproductive technologies. Issues such
      as intrapartum monitoring and operative interventions, especially relating to the
      second twin, provide a unique challenge in labour and delivery. Epidemiological
      and cohort data suggest that twins have a three-fold higher mortality rate than
      singletons, and that the second twin might have a better outcome if delivered by
      lower segment caesarean section. The recently completed Twin Birth Study has
      found that planned vaginal lower segment caesarean section is not advantageous to
      the fetus. In the light of this large randomised-controlled trial, vaginal
      delivery if twin A presents by the vertex is recommended as long as guidelines
      for the conduct of such delivery are followed. 

PMID- 24445021
TI  - Individual differences during acquisition predict shifts in generalization.
AB  - Learning to distinguish subtle differences in objects or events can impact how
      one generalizes. In some cases, training can cause novel events to appear more
      familiar or attractive than those actually experienced during training: the peak
      shift effect. This study examined whether individual differences in learning led
      to systematic patterns of generalization. Participants were trained to identify
      simulated birdsongs, and then tested on their ability to identify a target song
      presented among several similar songs that differed in pitch. Initial analysis
      showed that those attaining moderate proficiency at discriminating songs during
      training were more likely to shift than those performing poorly or proficiently.
      However, a neural network trained to output individuals' gradient dynamics using
      only performance during training as input found an additional set of training
      variables that predicted shift. Specifically, one subset of shifters had highly
      conservative response biases accompanied by very little change to perceptual
      sensitivity in training. These findings suggest that discrimination learning may
      only lead to generalization shifts in some individuals, and that all individuals
      who shift may not do so for the same reason. 

PMID- 24445022
TI  - Diagnosis and management of asthma in the elderly.
AB  - Bronchial asthma is one of the most common chronic diseases worldwide, and by
      definition not expected to recover with aging. However, the concept that asthma
      can affect older individuals has been largely denied in the past. In clinical
      practice, asthma that occurs in the most advanced ages is often diagnosed as
      COPD, thus leading to undertreatment or improper treatment. The heterogeneity of
      clinical and functional presentation of geriatric asthma, including the partial
      loss of reversibility and of the allergic component, contributes to this
      misconception. A large body of evidence has accumulated demonstrating that the
      prevalence of asthma in the most advanced ages is similar to that in younger
      ages. The frequent coexistence of comorbid conditions in older patients compared
      to younger asthmatics, together with age-associated changes of the human lung,
      may render the management of asthma a complicated task. The article addresses the
      main issues related to the diagnosis and treatment of asthma in the geriatric
      age. 

PMID- 24445024
TI  - Purine-stabilized green fluorescent gold nanoclusters for cell nuclei imaging
      applications.
AB  - We report facile one-pot synthesis of water-soluble green fluorescent gold
      nanoclusters (AuNCs), capped with 8-mercapto-9-propyladenine. The synthesized
      AuNCs were characterized by Fourier transform infrared (FTIR), powder X-ray
      diffraction (PXRD), transmission electron microscopy (TEM), (1)H NMR, and matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry. These nanoclusters show high photostability and biocompatibility.
      We observed that AuNCs stain cell nuclei with high specificity, where the
      mechanism of AuNC uptake was established through pathway-specific uptake
      inhibitors. These studies revealed that cell internalization of AuNCs occurs via
      a macropinocytosis pathway. 

PMID- 24445023
TI  - Hepatitis B virus infection in patients with metabolic syndrome: a complicated
      relationship. Results of a population based study.
AB  - BACKGROUND: The presence of hepatitis B infection (HBI) and metabolic syndrome
      (MS) at the same time constitutes a high risk for liver cirrhosis and potentially
      hepatocellular carcinoma. AIM: In this study we aim to explore the relationship
      between MS and HBI. METHODS: We used data from the cross-sectional HepaMeta study
      conducted in 2011 in Slovakia. Patients were tested for presence of MS, while
      lipid levels (total cholesterol, HDL, LDL, TG, apolipoprotein B100 and HBI (HBsAg
      and antiHBcIgG)) were also monitored. Viral load was measured in HBsAg positive
      patients. RESULTS: Altogether 855 patients were screened, MS was diagnosed in
      25.1% of patients and 7.9% of patients presented with HBI. AntiHBcIgG antibodies
      were present in 34.6% patients. HBI patients had lower levels of total and LDL
      cholesterol along with a decreased apolipoprotein B100 (4.54 +/- 0.84 vs. 5.0 +/-
      0.99 mmol/l, P=0.001; 2.29 +/- 0.58 vs. 2.6 +/- 0.68 mmol/l, P=0.001 and 0.71 +/-
      0.21 vs. 0.77 +/- 0.23 mmol/l, P=0.013 respectively). Patients diagnosed with MS
      had higher HBV DNA load than patients without MS - 1300.2 (95% CI 506.06-3440.41)
      vs. 7661.3 (95% CI 2008.17-29,228.06) IU/ml; P=0.011. HBI patients with TC and
      apolipoprotein B100 in the reference range had lower HBV DNA load than patients
      with high or low values of TC or apolipoprotein B100. CONCLUSION: Hepatitis B
      patients had lower levels of total and LDL cholesterol along with a decreased
      apolipoprotein B100. Viral load of chronic hepatitis B patients with MS was
      higher than that in patients without MS.

PMID- 24445025
TI  - Resolution of complex esthetic problems in abnormal anterior teeth: a clinical
      report.
AB  - A conservative treatment is presented for a patient with complex severe esthetic
      problems related to the presence of anomalous teeth. The patient showed a rare
      occurrence of macrodontia of the maxillary right lateral incisor and microdontia
      of the maxillary left lateral incisor. The treatment plan was conservative to
      avoid tooth extraction, periodontal tissue trauma, and the risk of an
      unpredictable esthetic outcome. A multidisciplinary treatment involving
      orthodontic extrusion, endodontic therapy, periodontal therapy, and minimally
      invasive restorations was performed. A successful outcome was observed after a 2
      year follow-up. 

PMID- 24445026
TI  - The use of a laser-level paralleling device for the fabrication of a unilateral
      auricular prosthesis.
AB  - This article describes the use of a laser-level paralleling device for the
      fabrication of a unilateral auricular prosthesis. Traditional methods require use
      of calipers to obtain orientation of contralateral auricular anatomy, which in
      turn can be difficult to replicate on the patient. The purpose of this clinical
      report is to describe a simple means to record unilateral auricular anatomy. 

PMID- 24445028
TI  - A technique for removing metal housing from acrylic resin.

PMID- 24445027
TI  - Marginal adaptation of zirconium dioxide copings: influence of the CAD/CAM system
      and the finish line design.
AB  - STATEMENT OF PROBLEM: Marginal adaptation is essential for the long-term success
      of dental restorations. Studies comparing the marginal gaps of computer-aided
      design/computer-aided manufacturing (CAD/CAM) restorations made from conventional
      and digital impressions are limited. PURPOSE: The purpose of this study was to
      evaluate the marginal adaptation of zirconium dioxide copings made with 2
      different CAD/CAM systems, the Lava All-Ceramic System (scanning definitive dies
      made with conventional impressions) and the Lava Chairside Oral Scanner (scanning
      directly from the prepared tooth). In addition, the influences of 2 different
      finish line configurations were also compared. MATERIAL AND METHODS: Forty human
      molar teeth were prepared to receive complete crowns. Twenty were prepared with a
      90-degree round shoulder and the other 20 with a 45-degree chamfer finish line.
      Zirconium dioxide copings were fabricated by using CAD/CAM technology. The
      specimens were randomized; they included 10 teeth with round shoulder and 10 with
      chamfer finish lines with the Lava All-Ceramic System, and 10 teeth with round
      shoulder and 10 with chamfer finish lines with the Lava Chairside Oral Scanner.
      The marginal gaps were measured at 5 points on each side with stereomicroscopy at
      40* magnification. Data were analyzed with 2-way ANOVA (alpha=.05). RESULTS: The
      mean values of the measured marginal gap for the round shoulder group were 52.66
      MUm with the Lava All-Ceramic System and 14.98 MUm with the Lava Chairside Oral
      Scanner. The mean values for the chamfer group were 64.06 MUm for the Lava All
      Ceramic System and 18.45 MUm for the Lava Chairside Oral Scanner. Differences
      were identified when the marginal gaps between the specimens with different
      CAD/CAM systems were compared. However, differences in the finish line design
      were identified only between the round shoulder and chamfer with the Lava All
      Ceramic System. CONCLUSIONS: Restorations fabricated with the Lava Chairside Oral
      Scanner displayed smaller marginal gaps than those made with the Lava All-Ceramic
      System. Nevertheless, all marginal gaps were within the range of clinical
      acceptability for both groups.

PMID- 24445029
TI  - Vacuum form sheet as a guide for fabrication of orbital prosthesis.
AB  - Rehabilitation with an orbital prosthesis is done when surgical reconstruction is
      not possible or affordable in patients with orbital exenteration. Fabrication of
      orbital prosthesis requires precision in placement of the ocular portion of the
      prosthesis on the facial moulage. This method describes the use of a vacuum
      formed sheet for making an orbital template that acts as a guide for achieving
      optimum orientation of the ocular portion of the prosthesis. 

PMID- 24445030
TI  - A technique to splint and verify the accuracy of implant impression copings with
      light-polymerizing acrylic resin.
AB  - Transferring the implant position from the mouth to the definitive cast is one of
      the most critical steps in implant prosthodontics. To achieve a passive fit of
      the prosthesis, an accurate implant impression is crucial because discrepancies
      can induce both biologic and technical complications. Analysis of available
      research data suggests that a direct (pick-up) impression technique with splinted
      copings is the technique of choice, particularly for multiple implants. However,
      the traditional method of splinting the copings with autopolymerizing acrylic
      resin is a technique-sensitive and time- consuming procedure. This report
      describes a straightforward method of splinting impression copings with light
      polymerizing acrylic resin, with minimal amount of autopolymerizing acrylic
      resin. The method also can be used to verify splinting accuracy. 

PMID- 24445031
TI  - Influence of multimode universal adhesives and zirconia primer application
      techniques on zirconia repair.
AB  - STATEMENT OF PROBLEM: More information is needed on the efficacy of the new
      universal adhesives and on the best 10-methacryloyloxydecyl dihydrogen phosphate-
      (MDP)-containing primer protocol to promote adhesion to zirconia. PURPOSE: The
      aim of this study was to evaluate the influence of 2 new multimode MDP-containing
      adhesives and several application protocols of a zirconia primer on the shear
      bond strength (SBS) of composite resin to zirconia. MATERIAL AND METHODS: Sixty
      zirconia (3Y-TZP) blocks were abraded (50 MUm Al2O3) and divided into 6
      experimental groups (n=10): one Z-Prime Plus coat without light polymerization;
      one Z-Prime Plus light-polymerized coat; two Z-Prime Plus coats without light
      polymerization; two Z-Prime Plus light-polymerized coats; All-Bond Universal; and
      ScotchBond Universal Adhesive. Multimode adhesives were applied according to the
      manufacturers' recommendations. After composite resin (Filtek Z250) light
      polymerization, the specimens were stored in distilled water (37 degrees C/48
      hours) and tested in shear (1 mm/min). Failure mode was classified as adhesive or
      mixed. Statistical analysis of the SBS data was performed with 1-way ANOVA
      followed by the Student-Newman-Keuls post hoc tests. Nonparametric tests (Kruskal
      Wallis) were used to analyze the failure mode data (alpha=.05). RESULTS: The
      ScotchBond Universal Adhesive, All-Bond Universal, and two Z-Prime Plus light
      polymerized coats groups showed a higher mean SBS than the other experimental
      groups (P<.05). The 3 groups with the lowest mean SBS registered 100% of adhesive
      failures. CONCLUSIONS: The new multimode adhesives tested were effective in
      promoting adhesion between composite resin and zirconia. Z-Prime Plus should be
      applied in 2 light-polymerized coats to promote SBS values similar to those of
      the new multimode adhesives.

PMID- 24445032
TI  - Complete integration of technology for improved reproduction of auricular
      prostheses.
AB  - The accurate reproduction of the form and surface details of missing body
      structures is an essential part of any successful prosthetic rehabilitation. It
      helps mask the prosthesis and gives confidence to the patient. This clinical
      report details the integration of multiple in-house digital technologies of laser
      scanning, rapid prototyping, and digital color scanning and formulating to
      improve the shape, texture, orientation, and color of auricular prostheses for 3
      patients with missing unilateral ears. A structured light laser scanner was used
      to digitize the patient's nondefect ear. The digitized data were then manipulated
      in specialist software and mirrored to reflect the opposing side. A rapid
      prototyping machine was used to manufacture a 3-dimensional (3D) model of the
      soft tissue required. This 3D mirrored ear model allowed the accurate
      reproduction of missing soft tissue. A color spectrometer was used to accurately
      reproduce the skin tones digitally and physically. 

PMID- 24445033
TI  - Alcohol use and positive screening results for depression and anxiety are highly
      prevalent among Chinese children with strabismus.
AB  - PURPOSE: To study associations between strabismus and alcohol use, anxiety, and
      depression among 10- to 17-year-old children in Guangdong, southern China.
      DESIGN: Cross-sectional, population-based study. METHODS: Among 7537 children
      aged 6-17 years from 9 randomly selected primary and middle schools, ocular
      alignment was assessed with the Hirschberg light reflex, cover-uncover testing,
      and alternate cover testing at distance (6 m) and near (40 cm). Additionally,
      4000 children (53.1%) aged 10+ years received self-administered questionnaires
      containing screening questions on alcohol use, anxiety, and depression. RESULTS:
      Examinations were completed on 7464 of 7537 subjects (99.0%), including 3928 boys
      (52.6%), with a mean age of 11.1 +/- 1.8 years. The prevalence of any strabismus,
      including exotropia (2.7%), esotropia (0.2%), and intermittent exotropia (3.9%),
      was 6.8%. Strabismus was more prevalent in urban students (7.3%) and female
      subjects (7.4%) compared to rural students (6.0%) and male subjects (6.2%) (all P
      < .05). In multivariate regression models, any strabismus was associated with
      older age and rural vs urban residence. Among 3903 children (97.6%) answering
      questionnaires, history of alcohol use (62.3% vs 36.3%) and positive screening
      responses for depression (26.0% vs 11.6%) and anxiety (10.3% vs 4.9%) were
      significantly (P < .01 for all) more common among children with strabismus.
      CONCLUSION: These Chinese children with strabismus had a significantly higher
      prevalence of alcohol use and possible markers of emotional problems than
      children without strabismus. Further research should focus on the appropriateness
      of classifying surgical treatment for strabismus as "cosmetic" (ineligible for
      reimbursement) under China's rural health insurance.

PMID- 24445034
TI  - Spontaneous resolution of vitreomacular traction demonstrated by spectral-domain
      optical coherence tomography.
AB  - PURPOSE: To evaluate the natural course of idiopathic vitreomacular traction
      (VMT) with spectral-domain optical coherence tomography (SDOCT) from the
      vitreomacular adhesion (VMA) stage to the spontaneous resolution of VMT. DESIGN:
      Prospective observational case series. METHODS: We studied the natural course of
      idiopathic VMT in 46 eyes (46 patients), divided into those that proceeded to
      spontaneous VMT resolution (12 cases) and those that remained at the VMT stage
      (34 cases). All patients were examined with SDOCT at regular 3-month intervals.
      We recorded the vitreomacular angle of VMA nasally and temporally, the horizontal
      diameter of VMA, macular thickness, visual acuity, photoreceptor layer, and
      external limiting membrane. RESULTS: In the 12 eyes that proceeded to spontaneous
      resolution, the vitreous adhesion angle had a mean increase of 38 degrees at VMT,
      compared to the angle at the VMA stage. In the 34 eyes that remained at the VMT
      stage, the mean angle of traction increased by only 1 degree throughout follow
      up. In all 46 patients, the angle at the VMT stage was significantly associated
      with traction resolution (nasally P = .001, temporally P < .001). The likelihood
      of resolution was more than 99% lower for patients with a VMT diameter >400 MUm
      compared with that of eyes with a VMT diameter <400 MUm. Patients with broad-type
      VMT remained at the same stage, whereas patients with V-type VMT had 80%
      probability of resolution. CONCLUSIONS: Spontaneous VMT resolution is negatively
      associated with the horizontal adhesion diameter. The strength of the traction
      exerted by the vitreous on the fovea seems to be positively related to the size
      of the vitreomacular angle.

PMID- 24445035
TI  - The impact of dietary fatty acids on macrophage cholesterol homeostasis.
AB  - The impact of dietary fatty acids in atherosclerosis development may be partially
      attributed to their effect on macrophage cholesterol homeostasis. This process is
      the result of interplay between cholesterol uptake and efflux, which are
      permeated by inflammation and oxidative stress. Although saturated fatty acids
      (SAFAs) do not influence cholesterol efflux, they trigger endoplasmic reticulum
      stress, which culminates in increased lectin-like oxidized LDL (oxLDL) receptor
      (LOX1) expression and, consequently, oxLDL uptake, leading to apoptosis.
      Unsaturated fatty acids prevent most SAFAs-mediated deleterious effects and are
      generally associated with reduced cholesterol efflux, although alpha-linolenic
      acid increases cholesterol export. Trans fatty acids increase macrophage
      cholesterol content by reducing ABCA-1 expression, leading to strong
      atherosclerotic plaque formation. As isomers of conjugated linoleic acid (CLAs)
      are strong PPAR gamma ligands, they induce cluster of differentiation (CD36)
      expression, increasing intracellular cholesterol content. Considering the
      multiple effects of fatty acids on intracellular signaling pathways, the purpose
      of this review is to address the role of dietary fat in several mechanisms that
      control macrophage lipid content, which can determine the fate of atherosclerotic
      lesions. 

PMID- 24445036
TI  - Bifidobacterium adolescentis protects from the development of nonalcoholic
      steatohepatitis in a mouse model.
AB  - To investigate the hypothesis that an oral supplementation of Bifidobacterium
      adolescentis protects against a diet-induced nonalcoholic steatohepatitis in a
      mouse model, C57BL/6 mice were fed either a Western-style or a control diet+/-tap
      water fortified with B. adolescentis (5*10(7) cfu/ml) ad libitum for 12 weeks.
      Mice fed a Western-style diet gained significantly more weight than mice fed a
      control diet and developed a mild steatohepatitis. Western-style diet fed groups
      concomitantly treated with B. adolescentis had significantly decreased liver
      damage, whereas portal endotoxin levels and toll-like receptor-4 protein levels
      as well as myeloid differentiation factor 88 mRNA were increased in livers of
      both Western-style diet fed groups. The protective effects of the B. adolescentis
      were associated with a significant attenuation of the formation of reactive
      oxygen species, activation of nuclear factor kappaB (NFkappaB) and induction of
      markers of inflammation in the liver. Taken together, our data suggest that an
      oral supplementation of the B. adolescentis attenuates diet-induced
      steatohepatitis, and this effect is associated with prevention from lipid
      peroxidation, NFkappaB activation and finally inflammation in the liver. 

PMID- 24445037
TI  - Daidzein promotes glucose uptake through glucose transporter 4 translocation to
      plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2
      diabetic model mice.
AB  - Daidzein shows estrogenic, antioxidant and antiandrogenic properties as well as
      cell cycle regulatory activity. However, the antihyperglycemic effect of daidzein
      remains to be elucidated. In this study, we investigated the in vitro effect of
      daidzein on glucose uptake, AMPK phosphorylation and GLUT4 translocation on
      plasma membrane in L6 myotubes and its in vivo antihyperglycmic effect in obese
      diabetic model db/db mice. Daidzein was found to promote glucose uptake, AMPK
      phosphorylation and GLUT4 translocation by Western blotting analyses in L6
      myotubes under a condition of insulin absence. Promotion by daidzein of glucose
      uptake as well as GLUT4 translocation to plasma membrane by immunocytochemistry
      was also demonstrated in L6 myoblasts transfected with a GLUT4 cDNA-coding
      vector. Daidzein (0.1% in the diet) suppressed the rises in the fasting blood
      glucose, serum total cholesterol levels and homeostasis model assessment index of
      db/db mice. In addition, daidzein supplementation markedly improved the AMPK
      phosphorylation in gastrocnemius muscle of db/db mice. Daidzein also suppressed
      increases in blood glucose levels and urinary glucose excretion in KK-Ay mice,
      another Type 2 diabetic animal model. These in vitro and in vivo findings suggest
      that daidzein is preventive for Type 2 diabetes and an antidiabetic
      phytochemical. 

PMID- 24445038
TI  - Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid
      extract: a randomized controlled trial.
AB  - Curcumin is a phytocompound found in the root of turmeric, a common herbal
      ingredient in many Asian cuisines. The compound contains anti-inflammatory
      activity, which is mediated through an up-regulation of adiponectin and reduction
      of leptin. Consumption of curcumin was shown to prevent some deteriorative
      conditions caused by inflammation, such as ulcerative colitis, rheumatoid
      arthritis and esophagitis, and so on. Inflammation-associated cardiovascular
      conditions such as atherosclerosis are common in diabetes patients. The anti
      inflammation effect of curcumin might be beneficial to prevent such condition in
      these patients. We aim to evaluate an antiatherosclerosis effect of curcumin in
      diabetes patients. Effects of curcumin on risk factors for atherosclerosis were
      investigated in a 6-month randomized, double-blinded and placebo-controlled
      clinical trial that included subjects diagnosed with type 2 diabetes. An
      atherosclerosis parameter, the pulse wave velocity, and other metabolic
      parameters in patients treated with placebo and curcumin were compared. Our
      results showed that curcumin intervention significantly reduced pulse wave
      velocity, increased level of serum adiponectin and decreased level of leptin.
      These results are associated with reduced levels of homeostasis model assessment
      insulin resistance, triglyceride, uric acid, visceral fat and total body fat. In
      summary, a 6-month curcumin intervention in type 2 diabetic population lowered
      the atherogenic risks. In addition, the extract helped to improve relevant
      metabolic profiles in this high-risk population. 

PMID- 24445039
TI  - Chronic supplementation of proanthocyanidins reduces postprandial lipemia and
      liver miR-33a and miR-122 levels in a dose-dependent manner in healthy rats.
AB  - Elevated postprandial triglycerides are associated with an increased risk of
      cardiovascular disease. Acute proanthocyanidin supplementation improves
      postprandial lipemia. Therefore, in this study, we evaluated whether a chronic
      treatment (3 weeks) of grape seed proanthocyanidins (GSPE) improves tolerance to
      lipid overload and represses liver microRNA (miRNA)-33a and miRNA-122 and their
      target genes as a mechanism to soften the elevated postprandial triglycerides in
      healthy rats. Additionally, the minimal GSPE chronic dose required to alter miRNA
      levels was determined by means of a dose-response experiment using 5, 15, 25 or
      50 mg of GSPE/kg body weight. GSPE repressed miR-33a and miR-122 liver expression
      and reduced postprandial lipemia in a dose-dependent manner. Significant effects
      were only observed at high levels of proanthocyanidin consumption, but moderate
      doses of proanthocyanidins were still able to modulate miRNA expression.
      Therefore, it can be suggested that a population with a normal intake of
      proanthocyanidin-rich foods can benefit from the modulation of miRNA expression.
      At the molecular level, this action can confer homeostatic robustness and will
      thus exert subtle changes in lipid metabolism, thereby reducing the risk
      associated with postprandial hyperlipemia. 

PMID- 24445040
TI  - Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9
      transgenic mouse model of Alzheimer's disease independent of brain amyloid
      deposition.
AB  - Dietary fish oil, providing n3 polyunsaturated fatty acids like eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), associates with reduced dementia risk
      in epidemiological studies and reduced amyloid accumulation in Alzheimer mouse
      models. We now studied whether additional nutrients can improve the efficacy of
      fish oil in alleviating cognitive deficits and amyloid pathology in APPswe/PS1dE9
      transgenic and wild-type mice. We compared four isocaloric (5% fat) diets. The
      fish oil diet differed from the control diet only by substituted fish oil.
      Besides fish oil, the plant sterol diet was supplemented with phytosterols, while
      the Fortasyn diet contained as supplements precursors and cofactors for membrane
      synthesis, viz. uridine-monophosphate; DHA and EPA; choline; folate; vitamins B6,
      B12, C and E; phospholipids and selenium. Mice began the special diets at 5
      months and were sacrificed at 14 months after behavioral testing. Transgenic
      mice, fed with control chow, showed poor spatial learning, hyperactivity in
      exploring a novel cage and reduced preference to explore novel odors. All fish
      oil-containing diets increased exploration of a novel odor over a familiar one.
      Only the Fortasyn diet alleviated the spatial learning deficit. None of the diets
      influenced hyperactivity in a new environment. Fish-oil-containing diets strongly
      inhibited beta- and gamma-secretase activity, and the plant sterol diet
      additionally reduced amyloid-beta 1-42 levels. These data indicate that
      beneficial effects of fish oil on cognition in Alzheimer model mice can be
      enhanced by adding other specific nutrients, but this effect is not necessarily
      mediated via reduction of amyloid accumulation. 

PMID- 24445041
TI  - The regulation of hepatic Pon1 by a maternal high-fat diet is gender specific and
      may occur through promoter histone modifications in neonatal rats.
AB  - The antioxidant (AOX) defense system is critical for combating whole-body
      oxidative stress, and the present study aimed to determine the consequences of a
      maternal high-fat (HF) diet on neonatal hepatic lipid accumulation, oxidative
      stress, the expression of AOX genes, as well as epigenetic histone modifications
      within Pon1, an AOX enzyme. Hepatic thiobarbituric acid reactive substances were
      significantly increased and nonesterified fatty acids decreased in offspring of
      HF-fed dams, while triglycerides increased in male but not female HF offspring
      when compared to controls (C). Pon1, Pon2, Pon3 and Sod2 were significantly
      increased in offspring of HF-fed dams when compared to C. However, the increase
      in Pon1 and Pon3 was only significant in male but not female offspring. When
      compared to C, the hepatic Pon1 promoter of male and female HF offspring had
      significantly more acetylated histone H4 as well as dimethylated histone H3 at
      lysine residue 4, which are both involved in transcriptional activation.
      Trimethylation of histone H3 at lysine residue 9, which is involved in
      transcriptional repression, was only associated with genes in females. Results
      from the present study reveal that a maternal HF diet affects hepatic metabolism
      in the neonate in a gender-specific manner, and these differences, in association
      with epigenetic modification of histones, may contribute to the known gender
      differences in oxidative balance. 

PMID- 24445042
TI  - Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent
      signaling pathway.
AB  - Curcumin, a natural and crystalline compound isolated from the plant Curcuma
      longa with low toxicity in normal cells, has been shown to protect against
      carcinogenesis and prevent tumor development. However, little is known about
      antimetastasis effects and mechanism of curcumin in lung cancer. Rac1 is an
      important small Rho GTPases family protein and has been widely implicated in
      cytoskeleton rearrangements and cancer cell migration, invasion and metastasis.
      In this study, we examined the influence of curcumin on in vitro invasiveness of
      human lung cancer cells and the expressions of Rac1. The results indicate that
      curcumin at 10 MUM slightly reduced the proliferation of 801D lung cancer cells
      but showed an obvious inhibitory effect on epidermal growth factor or
      transforming growth factor beta1-induced lung cancer cell migration and invasion.
      Meanwhile, we demonstrated that the suppression of invasiveness correlated with
      inhibition of Rac1/PAK1 signaling pathways and matrix metalloproteinase (MMP) 2
      and 9 protein expression by combining curcumin treatment with the methods of Rac1
      gene silence and overexpression in lung cancer cells. Laser confocal microscope
      also showed that Rac1-regulated actin cytoskeleton rearrangement may be involved
      in anti-invasion effect of curcumin on lung cancer cell. At last, through
      xenograft experiments, we confirmed the connection between Rac1 and the growth
      and metastasis inhibitory effect of curcumin in vivo. In summary, these data
      demonstrated that low-toxic levels of curcumin could efficiently inhibit
      migration and invasion of lung cancer cells through inhibition of Rac1/PAK1
      signaling pathway and MMP-2 and MMP-9 expression, which provided a novel insight
      into the molecular mechanism of curcumin against lung cancer. 

PMID- 24445043
TI  - Feeding with olive oil attenuates inflammation in dextran sulfate sodium-induced
      colitis in rat.
AB  - Chronic inflammation of long-term ulcerative colitis contributes to an increased
      risk of colon cancer. Few studies address whether extra-virgin olive oil (EVOO)
      intake suppresses inflammation, cell proliferation and signal transducers and
      activators of transcription (STAT) in the experimental colitis model. The aim of
      this study was to assess whether a 5% EVOO suppressed inflammation, increased
      cell proliferation and the expressions of STAT3 and STAT3 phosphorylation
      (pSTAT3) in dextran sulfate sodium (DSS)-induced colitis. Rats were administered
      DSS via drinking water (weight percentage: 4%) for 1 week with a 1-week recovery
      period for three cycles. Rats were divided into three groups: control group,
      standard diet without DSS; DSS group, standard diet+DSS; and DSS+EVOO group, EVOO
      diet (weight percentage: 5%)+DSS. Rats were sacrificed 5 weeks after DSS was
      first administered, and colonic damage was histologically and biochemically
      evaluated. As a result, chronic feeding of 5% EVOO attenuated inflammation. This
      was evaluated using a disease activity index, body weight loss and a histological
      score. Enhanced expressions of STAT3, pSTAT3, COX-2 and iNOS by DSS was
      attenuated by EVOO. In addition, EVOO attenuated increases in cell proliferation
      (PCNA) caused by DSS and recovered decreases in apoptosis (cleaved caspase-3). In
      conclusion, the study indicated that chronic feeding of 5% EVOO inhibited chronic
      inflammation in DSS-induced colitis in rats and also attenuated cell
      proliferation and recovered apoptosis in DSS colitis. 

PMID- 24445044
TI  - The inflammatory profile and liver damage of a sucrose-rich diet in mice.
AB  - It is still unclear if an isoenergetic, sucrose-rich diet leads to health
      consequences. AIMS: To investigate the effects of excessive sucrose within an
      isoenergetic diet on metabolic parameters in male C57BL/6 mice. METHODS: Animals
      were fed a control diet (10% fat, 8% sucrose - SC group), a high-sucrose diet
      (10% fat, 32% sucrose - HSu group), a high-fat diet (42% fat, 8% sucrose - HF
      group) or a high-fat/high-sucrose diet (42% fat, 32% sucrose - HF/HSu group) for
      8 weeks. RESULTS: Mice fed HF and HF/HSu diets gained more body mass (BM) and
      more body adiposity than SC- or Hsu-fed mice. Despite the unchanged BM and
      adiposity indices, HSu mice presented adipocyte hypertrophy, which was also
      observed in the HF and HF/HSu groups (P<.0001). The HF, HSu and HF/HSu mice were
      glucose intolerant and had elevated serum insulin levels (P<.05). The levels of
      leptin, resistin and monocyte chemotactic protein-1 increased, while the serum
      adiponectin decreased in the HF, HSu and HF/HSu groups (P<.05). In the adipose
      tissue, the HF, HSu and HF/HSu groups showed higher levels of leptin expression
      and lower levels of adiponectin expression in comparison with the SC group
      (P<.05). Liver steatosis was higher in the HF, HSu and HF/HSu groups than in the
      SC group (P<.0001). Hepatic cholesterol was higher in the HF and HF/HSu groups,
      while hepatic TG was higher in the HSu and HF/HSu groups (P<.05). In hepatic
      tissue, the sterol receptor element-binding protein-1c expression was increased
      in the HF, HSu and HF/HSu groups, unlike the peroxisome proliferator-activated
      receptor-alpha expression that decreased in the HF, HSu and HF/HSu groups in
      comparison with the SC group (P<.05). CONCLUSION: A sucrose-rich diet does not
      lead to a state of obesity but has the potential to cause changes in the
      adipocytes (hypertrophy) as well as glucose intolerance, hyperinsulinemia,
      hyperlipidemia, hepatic steatosis and increases in the number of inflammatory
      cytokines. The deleterious effects of a sucrose-rich diet in an animal model,
      even when the sucrose replaces starch isocalorically in the feed, can have far
      reaching consequences for health.

PMID- 24445045
TI  - Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the
      AMPK pathway in obese mice.
AB  - Obesity is associated with metabolic disorders. Sulforaphane, an isothiocyanate,
      inhibits adipogenesis and the occurrence of cardiovascular disease. In this
      study, we investigated whether sulforaphane could prevent high-fat diet (HFD)
      induced obesity in C57BL/6N mice. Mice were fed a normal diet (ND), HFD or HFD
      plus 0.1% sulforaphane (SFN) for 6 weeks. Food efficiency ratios and body weight
      were lower in HFD-SFN-fed mice than in HFD-fed mice. SFN attenuated HFD-induced
      visceral adiposity, adipocyte hypertrophy and fat accumulation in the liver.
      Serum total cholesterol and leptin, and liver triglyceride levels were lower in
      HFD-SFN-fed mice than in HFD-fed mice. SFN decreased the expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer-binding protein
      alpha (C/EBPalpha) and leptin in the adipose tissue of HFD-SFN mice and increased
      adiponectin expression. Phosphorylation of AMP-activated protein kinase alpha
      (AMPKalpha) and acetyl-CoA carboxylase in the adipose tissue of HFD-SFN-fed mice
      was elevated, and HMG-CoA reductase expression was decreased compared with HFD
      fed mice. Thus, these results suggest that SFN may induce antiobesity activity by
      inhibiting adipogenesis through down-regulation of PPARgamma and C/EBPalpha and
      by suppressing lipogenesis through activation of the AMPK pathway. 

PMID- 24445046
TI  - Early biomarkers identified in a rat model of a healthier phenotype based on
      early postnatal dietary intervention may predict the response to an obesogenic
      environment in adulthood.
AB  - Moderate maternal calorie restriction during lactation in rats provides certain
      protection against obesity in adult offspring. Hence, we used this model with 20%
      calorie restriction to identify early changes at the gene expression level in key
      tissues involved in energy homeostasis, as well as to assess whether they are
      maintained in adulthood, to consider them as potential biomarkers of metabolic
      health. Offspring of control and 20% calorie-restricted dams during lactation
      (CR) were followed. Animals were studied at weaning and at 6 months old under
      normal-fat (NF) diet and after being moved to a high-fat (HF) diet for the last 2
      months. Adult CR animals showed lower body weight, decreased hepatic lipids and
      improved circulating parameters vs. controls. At weaning, CR pups, in
      retroperitoneal white adipose tissue (rWAT), displayed lower messenger RNA (mRNA)
      levels of lipogenesis-related genes and higher mRNA levels of genes related with
      lipolysis and insulin signaling vs. controls. CR animals also showed lower
      hepatic mRNA levels of the lipogenesis-related gene sterol regulatory element
      binding protein 1c (SREBP1c) and higher mRNA levels of carnitine
      palmitoyltransferase 1 isoform a, adipose triglyceride lipase and long-form
      leptin receptor (ObRb). Some of these changes were sustained in adulthood under
      HF diet, and mRNA levels of IRS1 (rWAT) and of ObRb and SREBP1c (liver) in adult
      animals correlated with hepatic lipids and circulating parameters. In conclusion,
      the protective effects of moderate calorie restriction during lactation on
      offspring metabolic health are reflected in early changes at gene expression
      level in key tissues. Among them, transcript levels of IRS1 (rWAT) and of ObRb
      and SREBP1c (liver) emerge as particularly interesting as potential transcript
      based biomarkers of metabolic health. 

PMID- 24445047
TI  - Role of immunodeficient animal models in the development of fructose induced
      NAFLD.
AB  - Cellular and humoral immunity had been implicated in the pathogenesis of non
      alcoholic fatty liver disease (NAFLD). This study was designed to assess if T, B
      and natural killer (NK) cells are involved in the progress of NAFLD in mouse
      models after chronic fructose treatment. Mouse models that are deficient in
      either T cells, B cells or NK cells or lacking both T and B cells were fed with
      30% fructose solution for 12 weeks. Typical features of NAFLD, including the
      relative body weight, food and water intake, biochemical analytes, liver
      histology, NAFLD activity score, and glucose tolerance and insulin tolerance test
      were characterized. Further, the percentage of CD3, B220 and NK cells in
      peripheral-blood mononuclear cell, terminal deoxynucleotidyl transferase dUTP
      nick end labeling assay, immunodetection for hepatic apoptosis (p53) and for
      inflammation (TNFalpha) and quantitative real-time polymerase chain reaction for
      putative and inflammatory genes involved were determined. Our results conclude
      that mice deficient in T cells or NK cells fail to develop fructose induced NAFLD
      whereas the immunocompetent mice and mice with B-cell-specific defect developed
      NAFLD. Taken together, these data support that the onset of fructose-induced
      NAFLD is associated with involvement of T cells and NK cells in mice. 

PMID- 24445048
TI  - Maternal high-fat diet affects Msi/Notch/Hes signaling in neural stem cells of
      offspring mice.
AB  - Numerous research have begun to reveal the importance of maternal nutrition in
      offspring brain development. Particularly, the maternal obesity or exposure to
      high-fat diet has been strongly suggested to exert irreversible impact on the
      structure and function of offspring's brain. However, it remains obscure about
      whether neonatal neural stem cells (NSCs) in offspring's brain are susceptible to
      maternal exposure to high-fat diet. Here we focused on the alternation in the
      Notch signaling in NSCs derived from neonatal mice, which had been given birth by
      female mice with a high-fat diet and found that, in fact, the high-fat diet
      administration imposed effects on not only maternal mice, indicated by the
      accumulation of viscera fat as well as the increase in body weight and serum
      total cholesterol, but also NSCs in the offspring's brain, where significant
      increase was observed in the expression of genes, either downstream of Notch
      signaling or regulating this pathway, which have been shown essential for the
      maturation of NSCs. Therefore, our data provided the first evidence for the
      potential effect of maternal exposure to the high-fat diet on the Notch signaling
      pathway in offspring's NSCs, indicating this altered signaling response might
      contribute to a profound change in offspring's brains as a result of maternal
      high-fat diet prior to and during gestation. 

PMID- 24445049
TI  - Sesame oil mitigates nutritional steatohepatitis via attenuation of oxidative
      stress and inflammation: a tale of two-hit hypothesis.
AB  - Nonalcoholic fatty liver disease, the most common chronic liver disorder
      worldwide, comprises conditions from steatosis to nonalcoholic steatohepatitis
      (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular
      carcinoma. Sesame oil, a healthful food, increases resistance to oxidative
      stress, inflammation and protects against multiple organ injury in various animal
      models. We investigated the protective effect of sesame oil against nutritional
      steatohepatitis in mice. C57BL/6 J mice were fed with methionine-choline
      deficient (MCD) diet for 28 days to induce NASH. Sesame oil (1 and 2 ml/kg) was
      treated from 22nd to 28th day. Body weight, steatosis, triglycerides, aspartate
      transaminase, alanine transaminase, nitric oxide, malondialdehyde, tumor necrosis
      factor-alpha, interlukin-6, interleukin-1beta, leptin, and transforming growth
      factor-beta1 (TGF-beta1) were assessed after 28 days. All tested parameters were
      higher in MCD-fed mice than in normal control mice. Mice fed with MCD diet for 4
      weeks showed severe liver injury with steatosis, oxidative stress, and necrotic
      inflammation. In sesame-oil-treated mice, all tested parameters were
      significantly attenuated compared with MCD-alone mice. Sesame oil inhibited
      oxidative stress, inflammatory cytokines, leptin, and TGF-beta1 in MCD-fed mice.
      In addition, histological analysis showed that sesame oil provided significant
      protection against fibrotic collagen. We conclude that sesame oil protects
      against steatohepatitic fibrosis by decreasing oxidative stress, inflammatory
      cytokines, leptin and TGF-beta1. 

PMID- 24445050
TI  - Down-regulation of epidermal growth factor receptor by curcumin-induced UBE1L in
      human bronchial epithelial cells.
AB  - UBE1L, ubiquitin-activating enzyme E1-like, is the activating enzyme of
      ISG15ylation (ISG15, interferon stimulated gene 15). Loss of UBE1L and activation
      of epidermal growth factor receptor (EGFR) signaling are common events in lung
      carcinogenesis. Curcumin, a well-studied chemopreventive agent, is known to down
      regulate EGFR. The present study demonstrated that curcumin decreased EGFR
      expression in human bronchial epithelial (HBE) Beas-2B cells and lung cancer A549
      cells. For the first time, UBE1L was found to be induced by curcumin in HBE
      cells. Interestingly, overexpression of UBE1L reduced EGFR at posttranslational
      level in HBE cells. UBE1L triggered EGFR membrane internalization and promoted
      complex formation between ISG15 and EGFR. Curcumin decreased EGFR downstream
      signaling pAKT and nuclear factor kappaB (NF-kappaB). Overexpression or knockdown
      of UBE1L also resulted in down-regulation or up-regulation of phosphoinositide 3
      kinase/AKT/NF-kappaB correspondently. In human samples, there was an inverse
      relationship between UBE1L and EGFR/AKT/NF-kappaB in non-small cell lung cancer
      tissues and adjacent tissues. These results uncover a novel chemopreventive
      mechanism of curcumin in inducing UBE1L and down-regulating EGFR signaling in HBE
      cells. 

PMID- 24445051
TI  - Liquid fructose down-regulates liver insulin receptor substrate 2 and
      gluconeogenic enzymes by modifying nutrient sensing factors in rats.
AB  - High consumption of fructose-sweetened beverages has been linked to a high
      prevalence of chronic metabolic diseases. We have previously shown that a short
      course of fructose supplementation as a liquid solution induces glucose
      intolerance in female rats. In the present work, we characterized the fructose
      driven changes in the liver and the molecular pathways involved. To this end,
      female rats were supplemented or not with liquid fructose (10%, w/v) for 7 or 14
      days. Glucose and pyruvate tolerance tests were performed, and the expression of
      genes related to insulin signaling, gluconeogenesis and nutrient sensing pathways
      was evaluated. Fructose-supplemented rats showed increased plasma glucose
      excursions in glucose and pyruvate tolerance tests and reduced hepatic expression
      of several genes related to insulin signaling, including insulin receptor
      substrate 2 (IRS-2). However, the expression of key gluconeogenic enzymes,
      glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was reduced. These
      effects were caused by an inactivation of hepatic forkhead box O1 (FoxO1) due to
      an increase in its acetylation state driven by a reduced expression and activity
      of sirtuin 1 (SIRT1). Further contributing to FoxO1 inactivation, fructose
      consumption elevated liver expression of the spliced form of X-box-binding
      protein-1 as a consequence of an increase in the activity of the mammalian target
      of rapamycin 1 and protein 38-mitogen activated protein kinase (p38-MAPK). Liquid
      fructose affects both insulin signaling (IRS-2 and FoxO1) and nutrient sensing
      pathways (p38-MAPK, mTOR and SIRT1), thus disrupting hepatic insulin signaling
      without increasing the expression of key gluconeogenic enzymes. 

PMID- 24445052
TI  - Prenatal caloric restriction enhances DNA methylation and MeCP2 recruitment with
      reduced murine placental glucose transporter isoform 3 expression.
AB  - Diminished transplacental glucose transport plays an important role in prenatal
      calorie restriction (CR) induced reduction in fetal growth. Fetal growth
      restriction (FGR) has an impact in shaping the adult phenotype with
      transgenerational implications. To understand the mechanisms underlying prenatal
      CR-induced transplacental glucose transport, we examined the epigenetic
      regulation of placental glucose transporter (Glut1 and Glut3) expression. We
      restricted calories by 50% in C57BL6 pregnant mice from gestational days 10 to 19
      (CR; n=8) vs. controls (CON; n=8) and observed a 50% diminution in placental
      Glut3 expression (P<.05) with no effect on Glut1 expression by reverse
      transcription and quantitative real-time polymerase chain reaction (PCR). CR
      enhanced DNA methylation of a CpG island situated ~1000 bp upstream from the
      transcriptional start site of the glut3 gene, with no such effect on the glut1
      gene as assessed by methylation-sensitive PCR and bisulfite sequencing. Chromatin
      immunoprecipitation (ChIP) assays demonstrated enhanced MeCP2 binding to the CpG
      island of the glut3 gene in response to CR vs. CON (P<.05). Sequential ChIP
      demonstrated that enhanced MeCP2 binding of the glut3-(m)CpG island enhanced
      histone deacetylase 2 recruitment (P<.05) but interfered with Sp1 binding
      (P<.001), although it did not affect Sp3 or Creb/pCreb interaction. We conclude
      that late-gestation CR enhanced DNA methylation of the placental glut3 gene. This
      epigenetic change augmented specific nuclear protein-DNA complex formation that
      was associated with prenatal CR-induced reduction of placental glut3 expression
      and thereby transplacental glucose transport. This molecular complex provides
      novel targets for developing therapeutic interventions aimed at reversing FGR. 

PMID- 24445053
TI  - Biotinylation of the rhizobial cyclic beta-glucans and succinoglycans crucial for
      symbiosis with legumes.
AB  - The cyclic beta-glucans and succinoglycans produced by rhizobia are required for
      nodulation during symbiosis with legume hosts. However, only gene deletion
      analyses have been used to investigate their biological importance. For future
      studies on the physiological activity of those during symbiosis, biochemical
      methods need to be developed with separate carbohydrate compounds. Here, we
      isolated and purified rhizobial cellular carbohydrates using various
      chromatographic methods. Purified cyclic beta-glucans, cyclosophoraoses, were
      monofunctionalized with biotin using the following three steps: tosylation,
      azidation, and amination. The mono-6-amino-cyclosophoraoses were linked with
      biotinamidohexanoic acid N-hydroxysuccinimide ester. Succinoglycans and monomers
      were tagged with biotinamidocaproyl hydrazide at the reducing sugar via reductive
      amination. The resulting biotinylated rhizobial carbohydrates were characterized
      by Fourier transform infrared and nuclear magnetic resonance spectroscopy, matrix
      assisted laser desorption/ionization time-of-flight mass spectroscopy, and
      electrospray ionization mass spectrometry. The resulting neoglycoconjugates can
      be used as solid probes to study putative plant receptors and for non-invasive
      imaging for in vivo tracing. 

PMID- 24445054
TI  - Preface to a Special Issue: environmental radioactivity: legacy sites, Chernobyl
      and Fukushima.

PMID- 24445055
TI  - Physical properties, structure, and shape of radioactive Cs from the Fukushima
      Daiichi Nuclear Power Plant accident derived from soil, bamboo and shiitake
      mushroom measurements.
AB  - We conducted an elution experiment with contaminated soils using various aqueous
      reagent solutions and autoradiography measurements of contaminated bamboo shoots
      and shiitake mushrooms to determine the physical and chemical characteristics of
      radioactive Cs from the Fukushima Daiichi Nuclear Power Plant accident. Based on
      our study results and data in the literature, we conclude that the active Cs
      emitted by the accident fell to the ground as granular non-ionic materials.
      Therefore, they were not adsorbed or trapped by minerals in the soil, but instead
      physically adhere to the rough surfaces of the soil mineral particles. Granular
      Cs* can be transferred among media, such as soils and plants. The physical
      properties and dynamic behavior of the granular Cs* is expected to be helpful in
      considering methods for decontamination of soil, litter, and other media. 

PMID- 24445056
TI  - Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear
      factor kappa B activation in Kupffer cells.
AB  - BACKGROUND: The inflammatory response after hepatic ischemia reperfusion (I/R)
      contributes to liver dysfunction and failure after transplantation. Butyrate is a
      four-carbon fatty acid, normally produced by bacterial fermentation of fiber in
      mammalian intestines, with anti-inflammatory activities. The purpose of the
      present study was to investigate the protective effect of butyrate
      preconditioning, if any, against hepatic I/R injury in rats and the underlying
      mechanisms involved. METHODS: Male Sprague-Dawley rats were subjected to a
      partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle
      or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was
      evaluated by biochemical and histopathologic examinations. Neutrophil
      infiltration was measured by myeloperoxidase (MPO) activity. The expression of
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was measured by
      enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase
      polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF
      kappaB) p65 was determined by immunohistochemistry and Western blot analysis.
      RESULTS: Butyrate treatment markedly improved hepatic function and histology, as
      indicated by reduced transaminase levels and ameliorated tissue pathologic
      changes. The expression of tumor necrosis factor-alpha, interleukin-6, and
      myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R
      induced nuclear translocation of NF-kappaB p65 in Kupffer cells. CONCLUSION: Our
      results suggest that butyrate alleviates I/R-induced liver injury, possibly by
      suppressing inflammatory factors production and preventing NF-kappaB activation
      in Kupffer cells.

PMID- 24445057
TI  - Using multi-channel level sets to measure the cytoplasmic localization of HCMV
      pUL97 in GFP-B-gal fusion constructs.
AB  - Human cytomegalovirus UL97-encoded protein kinase (pUL97) phosphorylates cellular
      and viral proteins and is critical for viral replication. To quantify the
      efficiency of nuclear translocation and to elucidate the role of putative nuclear
      localization signal (NLS) elements, immunofluorescence analysis of different
      pUL97 expression constructs was performed. Since manual quantitation of
      respective expression levels lacks objectivity and reproducibility, and is time
      consuming as well, a computer-based model is established. This model enables
      objective quantitation of the degree of cytoplasmic localization lambda. To
      determine the degree of cytoplasmic localization of different pUL97-GFP-beta-gal
      fusion proteins automatically, a multi-channel segmentation of the nucleus and
      cytoplasm of transfected HeLa cells is performed in DAPI and GFP micrographs. A
      watershed transform-based segmentation scheme is used for the segmentation of the
      cell nuclei. Subsequently, the cytoplasm is segmented using a fast marching level
      set method. Based on the segmentation of cell nuclei and cytoplasm, lambda can be
      determined for each HeLa cell by quantitation of the ratio of average signal
      intensity outside and inside the nucleus. The degree of cytoplasmic localization
      of an individual construct is then determined by evaluating the average and
      standard deviation of lambda for the corresponding HeLa cells. Evaluation
      demonstrates that nuclear transport of pUL97 is a multilayered mechanism
      resulting in different efficiencies of nuclear translocation between a small and
      a large isoform and objective quantitation of the cytoplasmic localization is
      possible with a high accuracy (96.7% and 94.3%). 

PMID- 24445058
TI  - Propagation and titration of Alkhumra hemorrhagic fever virus in the brains of
      newborn Wistar rats.
AB  - Alkhumra hemorrhagic fever virus (AHFV) is a novel flavivirus identified first in
      Saudi Arabia. In this study, successful propagation of AHFV in the brains of
      newborn Wistar rats is described and the median rat lethal dose (RLD50) is
      determined. AHFV-RNA-positive human sera diluted 1:10 were injected
      intracerebrally into 16, <=24h old rats. Post-inoculation, the rats were observed
      daily for 30 days. Brains of moribund rats were tested for AHFV-RNA using RT-PCR
      and cultured in LLC-MK2 cells. The titer of the isolated virus was determined and
      expressed in median tissue culture infectious dose (TCID50). To determine the
      RLD50, AHFV brain suspension was 10-fold diluted serially and each dilution was
      inoculated in the cerebral hemispheres of 10 rats for a total of 90 rats. Three
      days post-inoculation, the rats developed tremor, irritability, convulsion,
      opisthotonus, and spastic paresis starting in the hind limbs and ascending to
      involve the whole body. All infected rats died within 3-7 days with
      histopathologically confirmed meningoencephalitis. AHFV-RNA was detected in the
      brains of all infected rats and the virus titer was 10(9.4) RLD50/ml. The virus
      titer in LLC-MK2 was 10(8.2) TCID50/ml. In conclusion, AHFV was propagated
      successfully to high titers in the brains of newborn Wistar rats. 

PMID- 24445060
TI  - Mitochondrial DNA haplogroups and risk of new-onset diabetes among tacrolimus
      treated renal transplanted patients.
AB  - BACKGROUND AND AIMS: Tacrolimus (Tac) is an immunosuppressive drug widely used to
      avoid organ rejection. New-onset diabetes after transplantation (NODAT) is a
      major complication among transplanted patients who receive Tac. The increased
      risk for NODAT could be partly mediated by the effect of Tac on mitochondria from
      pancreatic beta-cells. Common and rare mitochondrial DNA variants have been
      linked to the risk of diabetes. Our aim was to determine whether mtDNA
      polymorphisms/haplogroups were associated with NODAT in Tac-treated kidney
      transplanted. METHODS: Seven polymorphisms that define the common European
      haplogroups were determined in 115 NODAT and 197 no-NODAT patients. RESULTS:
      Haplogroup H was significantly more frequent in the NODAT group (50% vs. 35%;
      p=0.01, OR=1.82). There was no difference between patients without and with
      (n=106) D2M prior to the transplant. CONCLUSIONS: Mitochondrial haplogroup H was
      associated with the risk for NODAT among Tac-treated transplanted patients. The
      reported differences between the mtDNA variants could explain the increased NODAT
      risk among H-patients.

PMID- 24445059
TI  - Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell
      migration via Nox1-dependent reactive oxygen species generation.
AB  - Fat1 is an atypical cadherin that controls vascular smooth muscle cell (VSMC)
      proliferation and migration. Nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase 1 (Nox1) is an important source of reactive oxygen species (ROS) in
      VSMCs. Angiotensin II (Ang II) induces the expression and/or activation of both
      Fat1 and Nox1 proteins. This study tested the hypothesis that Ang II-induced Fat1
      activation and VSMC migration are mediated by Nox1-dependent ROS generation and
      redox signaling. Studies were performed in cultured VSMCs from Sprague-Dawley
      rats. Cells were treated with Ang II (1 MUmol/L) for short (5 to 30 min) or long
      term stimulations (3 to 12 h) in the absence or presence of the antioxidant
      apocynin (10 MUmol/L), extracellular-signal-regulated kinases 1/2 (Erk1/2)
      inhibitor PD98059 (1 MUmol/L), or Ang II type 1 receptor (AT1R) valsartan (1
      MUmol/L). siRNA was used to knockdown Nox1 or Fat1. Cell migration was determined
      by Boyden chamber assay. Ang II increased Fat1 mRNA and protein levels and
      promoted Fat1 translocation to the cell membrane, responses that were inhibited
      by AT1R antagonist and antioxidant treatment. Downregulation of Nox1 inhibited
      the effects of Ang II on Fat1 protein expression. Nox1 protein induction, ROS
      generation, and p44/p42 MAPK phosphorylation in response to Ang II were prevented
      by valsartan and apocynin, and Nox1 siRNA inhibited Ang II-induced ROS
      generation. Knockdown of Fat1 did not affect Ang II-mediated increases in Nox1
      expression or ROS. Inhibition of p44/p42 MAPK phosphorylation by PD98059
      abrogated the Ang II-induced increase in Fat1 expression and membrane
      translocation. Knockdown of Fat1 inhibited Ang II-induced VSMC migration, which
      was also prevented by valsartan, apocynin, PD98059, and Nox1 siRNA. Our findings
      indicate that Ang II regulates Fat1 expression and activity and induces Fat1
      dependent VSMC migration via activation of AT1R, ERK1/2, and Nox1-derived ROS,
      suggesting a role for Fat1 downstream of Ang II signaling that leads to vascular
      remodeling.

PMID- 24445061
TI  - Home spirometry as early detector of azithromycin refractory bronchiolitis
      obliterans syndrome in lung transplant recipients.
AB  - BACKGROUND: To evaluate the utility of home spirometry (HS) versus office
      spirometry (OS) in assessing treatment response to azithromycin in bronchiolitis
      obliterans syndrome (BOS). METHODS: 239 Lung transplant recipients were
      retrospectively studied. DeltaFEV1 +/- 10% from FEV1 at azithromycin initiation
      for >=7 consecutive days in HS or >=2 measures in OS were taken as cut-off for
      response or progression. RESULTS: Based upon HS, 161/239 (67%) patients were
      progressive despite macrolide, 19 of who exhibited transient improvement in FEV1
      (11%). Time to progression was 29 (13-96) days earlier with HS than in OS. Forty
      six (19%) recipients responded in HS after median 81 (22-343) days, whilst 22%
      remained stable. Concordance in azithromycin treatment response between OS and HS
      was observed in 210 of 239 patients (88%). Response or stabilization conferred
      significant improvement in survival (p = 0.005). Transient azithromycin
      responders demonstrated improved survival when compared to azithromycin
      refractory patients (p = 0.034). CONCLUSIONS: HS identified azithromycin
      refractory patients significantly earlier than OS, possibly facilitating
      aggressive treatment escalation that may improve long-term outcome. Treatment
      response to azithromycin should be assessed 4 weeks after initiation. Responders
      demonstrated best survival, with even transient response conferring benefit.
      Macrolide-refractory BOS carried the worst prognosis.

PMID- 24445062
TI  - Mortality in non-cystic fibrosis bronchiectasis: a prospective cohort analysis.
AB  - INTRODUCTION: There is limited data on mortality and associated morbidity in non
      cystic fibrosis bronchiectasis (NCFB). Our aim was to analyze the overall
      mortality for all newly diagnosed patients from June 2006 onwards and to evaluate
      risk factors for mortality in this cohort. METHODS: 245 patients who had a new
      diagnosis of NCFB between June 2006 and October 2012 at the University Hospital
      of Leuven, Belgium, were included in the analysis. Death was analyzed until end
      of November 2013. All patients had chest HRCT scan confirming the presence of
      bronchiectatic lesions and had symptoms of chronic productive cough. Univariate
      and multivariate Cox proportional hazard survival regression analysis was used to
      estimate hazard ratios (HR) and their 95% confidence intervals (CI) of variables
      possibly predicting mortality. RESULTS: Overall mortality in NCFB patients who
      had a median follow-up of 5.18 years was 20.4%. Patients with NCFB and associated
      chronic obstructive pulmonary disease (COPD) had a mortality of 55% in that
      period. Univariate analysis showed higher mortality according to age, gender,
      smoking history, Pseudomonas aeruginosa status, spirometry, radiological extent,
      total number of sputum bacteria and underlying etiology. Multivariate analysis
      showed significant higher mortality with increasing age (HR = 1.045; p = 0.004),
      with increasing number of lobes affected (HR = 1.53; p = 0.009) and when patients
      had COPD associated NCFB (HR = 2.12; p = 0.038). The majority of the 50 deaths
      were respiratory related (n = 29; 58%). CONCLUSION: NCFB patients with associated
      COPD disease had the highest mortality rates compared to the other NCFB patients.
      Additional risk factors for lower survival were increasing age and number of
      lobes affected.

PMID- 24445064
TI  - Health-related quality of life after transcatheter aortic valve implantation in
      elderly patients with severe aortic stenosis.
AB  - BACKGROUND: Severe aortic stenosis may affect both normal daily living and
      survival. Transcatheter aortic valve implantation (TAVI) has become an
      appropriate alternative to surgery for elderly patients with high surgical risk,
      and it results in improved survival in this population. OBJECTIVE: To describe
      health-related quality of life (QoL) before, and at 1 and 6 months after TAVI.
      SETTING: Cardiovascular Department, Toulouse University Hospital, France.
      METHODS: One hundred sixty-four consecutive patients with at least 6 months
      follow-up who underwent TAVI in our institution between February 2009 and June
      2011 were enrolled in the study. Of this population, 73 (mean age: 82.3 +/- 7.3
      years, 56% men) completed QoL assessment using the EuroQOL Five Dimensions (EQ
      5D) questionnaire and a visual analogue scale at baseline, and at 1 and 6 months.
      At each visit, medical data and New York Heart Association functional class were
      collected. RESULTS: The median preprocedure EQ-5D index value (interquartile
      range) was 0.66 (range, 0.36-0.78) showing severely impaired QoL in almost all
      patients. Significant improvement occurred from baseline to 1 month of follow-up
      in EQ-5D index value [0.73 (range, 0.59-0.79)] and this was maintained at 0.73
      (range, 0.62-0.81) at 6 months. The improvement was significant for 3 dimensions
      of the EQ-5D score at the 6-month follow-up: usual activities in 43.8% of
      patients (P < .001); anxiety/depression in 37% (P < .001) and pain/discomfort in
      28.8% (P < .05). Mean New York Heart Association class improved significantly
      from 3.24 at baseline to 2.04 at 1 month and 1.89 at 6 months. CONCLUSIONS: In
      high-risk patients with severe aortic stenosis, QoL and health status improved
      substantially at 1 month and improvement persisted 6 months after TAVI.

PMID- 24445063
TI  - Obesity and physical frailty in older adults: a scoping review of lifestyle
      intervention trials.
AB  - Many frail older adults are thin, weak, and undernourished; this component of
      frailty remains a critical concern in the geriatric field. However, there is also
      strong evidence that excessive adiposity contributes to frailty by reducing the
      ability of older adults to perform physical activities and increasing metabolic
      instability. Our scoping review explores the impact of being obese on physical
      frailty in older adults by summarizing the state of the science for both clinical
      markers of physical function and biomarkers for potential underlying causes of
      obesity-related decline. We used the 5-stage methodological framework of Arksey
      and O'Malley to conduct a scoping review of randomized trials of weight loss
      and/or exercise interventions for obesity (body mass index >= 30 kg/m(2)) in
      older adults (aged >60 years), examining the outcomes of inflammation, oxidative
      stress, and lipid accumulation in muscle, as well as direct measures of physical
      function. Our initial search yielded 212 articles; exclusion of cross-sectional
      and observational studies, cell culture and animal studies, disease-specific
      interventions, and articles published before 2001 led to a final result of 21
      articles. Findings of these trials included the following major points. The
      literature consistently confirmed benefits of lifestyle interventions to physical
      function assessed at the clinical level. Generally speaking, weight loss alone
      produced a greater effect than exercise alone, and the best outcomes were
      achieved with a combination of weight loss and exercise, especially exercise
      programs that combined aerobic, resistance, and flexibility training. Weight loss
      interventions tended to reduce markers of inflammation and/or oxidative damage
      when more robust weight reduction was achieved and maintained over time, whereas
      exercise did not change markers of inflammation. However, participation in a
      chronic exercise program did reduce the oxidative stress induced by an acute bout
      of exercise. Weight loss interventions consistently reduced lipid accumulation in
      the muscle; however, in response to exercise, 3 studies showed an increase and 2
      a decrease in muscle lipid infiltration. In summary, this scoping review
      identified strong clinical evidence that weight reduction and/or exercise
      interventions can improve physical function and biomarkers of physical
      dysfunction among overweight/obese older adults, supporting the suggestion that
      excessive adiposity contributes to physical frailty. However, the evidence also
      suggests a complexity of metabolic influences, both systemically and within
      muscle, which has not been elucidated to date. Considerable further study is
      needed to examine the mechanisms by which lifestyle interventions influence
      physical frailty before the net impact of such interventions can be fully
      understood. 

PMID- 24445065
TI  - Age-related differences in sagittal-plane knee function at heel-strike of walking
      are increased in osteoarthritic patients.
AB  - OBJECTIVE: To compare age-related patterns of gait with patterns associated with
      knee osteoarthritis (OA), the following hypotheses were tested: (H1) The sagittal
      plane knee function during walking is different between younger and older
      asymptomatic subjects; (H2) The age-related differences in H1 are increased in
      patients with knee OA. DESIGN: Walking trials were collected for 110 participants
      (1.70 +/- 0.09 m, 80 +/- 14 kg). There were 29 younger asymptomatic subjects (29
      +/- 4 years) and 81 older participants (59 +/- 9 years), that included 27
      asymptomatic subjects and 28 and 26 patients with moderate and severe medial knee
      OA. Discrete variables characterizing sagittal-plane knee function were compared
      among the four groups using ANOVAs. RESULTS: During the heel-strike portion of
      the gait cycle at preferred walking speed, the knee was less extended and the
      shank less inclined in the three older groups compared to the younger
      asymptomatic group. There were similar differences between the severe OA group
      and the older asymptomatic and moderate OA groups. Both OA groups also had the
      femur less posterior relative to the tibia and smaller extension moment than the
      younger group. During terminal stance, the severe OA group had the knee less
      extended and smaller knee extension moment than the younger asymptomatic and
      older moderate OA groups. CONCLUSIONS: The differences in knee function,
      particularly those during heel-strike which were associated with both age and
      disease severity, could form a basis for looking at mechanical risk factors for
      initiation and progression of knee OA on a prospective basis.

PMID- 24445066
TI  - Detection of CREB phosphorylation via Zr (IV) ion mediated signal amplification.
AB  - Phosphorylation of protein plays a vital regulatory role in a variety of
      biological processes. We herein report a novel method to assay the level of
      phosphorylated cAMP-response element binding protein (CREB) via Zr(4+) mediated
      signal amplification using gold nanoparticle/DNA/methylene blue (GNP/DNA/MB)
      nanocomposites. In this method the probe DNA immobilized at a gold electrode
      surface can specifically and efficiently recognize the phosphorylated target
      protein CREB. Then Zr(4+) links the phosphorylated CREB with GNP/DNA/MB
      nanocomposites by coordinating the phosphate groups on both CREB and the
      nanocomposites. Since the nanocomposites can provide high sensitivity (limit of
      detection: 0.25 nM) for the detection, efficient and highly sensitive bioanalysis
      of the expression level of phosphorylated protein CREB in human placenta tissues
      has also been conducted in this work. Our method is reported which shows
      acceptable stability, reproducibility for assaying of the protein phosphorylation
      states in real biosamples under physiological and pathological conditions with
      great potential for clinical applications in future.

PMID- 24445067
TI  - One-pot synthesis of high fluorescent carbon nanoparticles and their applications
      as probes for detection of tetracyclines.
AB  - Herein, a novel strategy for synthesizing fluorescent carbon nanoparticles (CPs)
      with a quantum yield of approximately 7.1% has been well established by mixing l
      cysteine, diphosphorus pentoxide and water. Compared with other current
      protocols, the method described here displayed various advantages including
      friendly manipulations, low cost, and rapid reactions. Subsequently, we applied
      the CPs prepared here for detections of tetracyclines (TCs). Briefly, the
      fluorescence intensity of CPs was quenched once TCs were introduced. Based on
      this phenomenon, TCs were analyzed respectively accompanyed with satisfactory
      detection limits and linear ranges. Significantly, the practicability of this
      sensing method was further validated by assaying TC in human urine samples and
      pharmaceutical preparations, confirming its potential to broaden avenues for
      detecting TCs. Additionally, the CPs could serve as fluorescent powder and ink
      followed by a simple post-treatment, suggesting their promising applications. 

PMID- 24445068
TI  - Enzyme-free and label-free ultrasensitive electrochemical detection of DNA and
      adenosine triphosphate by dendritic DNA concatamer-based signal amplification.
AB  - Hybridization chain reaction (HCR) strategy has been well developed for the
      fabrication of various biosensing platforms for signal amplification. Herein, a
      novel enzyme-free and label-free ultrasensitive electrochemical DNA biosensing
      platform for the detection of target DNA and adenosine triphosphate (ATP) was
      firstly proposed, in which three auxiliary DNA probes were ingeniously designed
      to construct the dendritic DNA concatamer via HCR strategy and used as
      hexaammineruthenium(III) chloride (RuHex) carrier for signal amplification. With
      the developed dendritic DNA concatamer-based signal amplification strategy, the
      DNA biosensor could achieve an ultrasensitive electrochemical detection of DNA
      and ATP with a superior detection limit as low as 5 aM and 20 fM, respectively,
      and also demonstrate a high selectivity for DNA and ATP detection. The currently
      proposed dendritic DNA concatamer opens a promising direction to construct
      ultrasensitive DNA biosensing platform for biomolecular detection in bioanalysis
      and clinical biomedicine, which offers the distinct advantages of simplicity and
      cost efficiency owing to no need of any kind of enzyme, chemical modification or
      labeling.

PMID- 24445069
TI  - Enhancement of bioelectricity generation by cofactor manipulation in microbial
      fuel cell.
AB  - Microbial fuel cells (MFCs) are promising for harnessing bioenergy from various
      organic wastes. However, low electricity power output (EPT) is one of the major
      bottlenecks in the practical application of MFCs. In this study, EPT improvement
      by cofactor manipulation was explored in the Pseudomonas aeruginosa-inoculated
      MFCs. By overexpression of nadE (NAD synthetase gene), the availability of the
      intracellular cofactor pool (NAD(H/(+))) significantly increased, and delivered
      approximately three times higher power output than the original strain (increased
      from 10.86 MUW/cm(2) to 40.13 MUW/cm(2)). The nadE overexpression strain showed
      about a onefold decrease in charge transfer resistance and higher electrochemical
      activity than the original strain, which should underlie the power output
      improvement. Furthermore, cyclic voltammetry, HPLC, and LC-MS analysis showed
      that the concentration of the electron shuttle (pyocyanin) increased
      approximately 1.5 fold upon nadE overexpression, which was responsible for the
      enhanced electrochemical activity. Thus, the results substantiated that the
      manipulation of intracellular cofactor could be an efficient approach to improve
      the EPT of MFCs, and implied metabolic engineering is of great potential for EPT
      improvement.

PMID- 24445071
TI  - The effect of tributyltin chloride on Caenorhabditis elegans germline is mediated
      by a conserved DNA damage checkpoint pathway.
AB  - Tributyltin (TBT), one of the environmental pollutants, has been shown to impact
      the reproduction of animals. However, due to the lack of appropriate animal
      model, analysis of the affected molecular pathways in germ cells is lagging and
      has been particularly challenging. In the present study, we investigated the
      effects of tributyltin chloride (TBTCL) on the nematode Caenorhabditis elegans
      germline. We show that exposure of C. elegans to TBTCL causes significantly
      elevated level of sterility and embryonic lethality. TBTCL exposure results in an
      increased number of meiotic DNA double-strand breaks in germ cells, subsequently
      leading to activated DNA damage checkpoint. Exposing C. elegans to TBTCL causes
      dose- and time-dependent germline apoptosis. This apoptotic response was blocked
      in loss-of-function mutants of hus-1 (op241), mrt-2 (e2663) and p53/cep-1
      (gk138), indicating that checkpoints and p53 are essential for mediating TBTCL
      induced germ cell apoptosis. Moreover, TBTCL exposure can inhibit germ cell
      proliferation, which is also mediated by the conserved checkpoint pathway. We
      thereby propose that TBT exhibits its effects on the germline by inducing DNA
      damage and impaired maintenance of genomic integrity.

PMID- 24445070
TI  - The role of cytochrome P450 2B6 and 2B4 substrate access channel residues
      predicted based on crystal structures of the amlodipine complexes.
AB  - Recent X-ray crystal structures of human cytochrome P450 2B6 and rabbit
      cytochrome P450 2B4 in complex with amlodipine showed two bound ligand molecules,
      one in the active site and one in the substrate access channel. Based on the X
      ray crystal structures, we investigated the interactions of P450 2B4 and 2B6 with
      amlodipine using absorbance spectroscopy, and determined the steady-state
      kinetics of 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin
      oxidation by some access channel mutants to evaluate the functional role of these
      residues in substrate turnover. The results of absorbance titrations are
      consistent with a simple mechanism with two parallel binding events that result
      in the formation of the enzyme complex with two molecules of amlodipine. Using
      this model we were able to resolve two separate ligand-binding events, which are
      characterized by two distinct KD values in each enzyme. The access channel
      mutants R73K in P450 2B6 and R73K, V216W, L219W, and F220W in P450 2B4 showed a
      significant decrease in kcat/KM with the both substrates. Overall, the results
      suggest that P450 2B4 and 2B6 form an enzyme complex with two molecules of
      amlodipine in solution, and R73, V216, L219 and F220 in P450 2B4 may play an
      important role in substrate metabolism. 

PMID- 24445072
TI  - Exercise modifies amphetamine relapse: behavioral and oxidative markers in rats.
AB  - Exercise has been reported to attenuate rewarding symptoms related to addictive
      drugs mainly by affecting the brain neuroplasticity and neurotransmission. In
      this study, we investigated the influence of physical exercise on the behavioral
      and enzymatic status related to drug relapse in rats. Animals were primarily
      treated with amphetamine (AMPH; 4.0 mg/kg, i.p.) or vehicle (C; NaCl 0.9%
      solution) in the conditioned place preference (CPP) paradigm for 14 days. Half of
      each experimental group was then submitted to swimming sessions (60 min/day, 5
      days/week) for 5 weeks. Animals were re-exposed to AMPH- or vehicle-CPP paradigm
      for another 3 days, in order to observe drug relapse and anxiety-like symptoms,
      which were observed 24h after AMPH reconditioning in CPP, and elevated plus maze
      (EPM), respectively, and brain biochemical evaluations were carried out
      subsequently. While AMPH was related to place preference and anxiety, indicating
      drug addiction and abstinence symptoms, respectively, physical activity was able
      to prevent relapse symptoms after AMPH reconditioning, as observed through
      consecutive decreased CPP and anxiety-like symptoms. In addition, AMPH exposure
      increased reactive species (RS) generation and protein carbonyl (PC) levels
      together with decreased activity of catalase- and Na(+)K(+)-ATPase in
      hippocampus. On the other hand, while all AMPH-induced effects were prevented by
      physical activity, there was a negative correlation between PC levels (r=0.65;
      p<0.003) and CAT activity, and a positive correlation between RS generation and
      PC levels (r=0.54; r=0.52, p<0.05) with AMPH-CPP after exercise. These results
      indicate that exercise has a clear beneficial influence on the prevention of
      psychostimulant drug relapse.

PMID- 24445074
TI  - Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial
      recognition memory in ovariectomized rats.
AB  - In ovariectomized rats, administration of estradiol, or selective estrogen
      receptor agonists that activate either the alpha or beta isoforms, have been
      shown to enhance spatial cognition on a variety of learning and memory tasks,
      including those that capitalize on the preference of rats to seek out novelty.
      Although the effects of the putative estrogen G-protein-coupled receptor 30
      (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks,
      the effects of activation of GPR30 receptors on tasks that depend on the
      preference of rats to seek out spatial novelty remain to be determined.
      Therefore, the aim of the current study was to determine if short-term treatment
      of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on
      spatial recognition memory observed following short-term estradiol treatment. In
      Experiment 1, ovariectomized rats treated with a low dose (1 MUg) of estradiol 48
      h and 24 h prior to the information trial of a Y-maze task exhibited a preference
      for the arm associated with the novel environment on the retention trial
      conducted 48 h later. In Experiment 2, treatment of ovariectomized rats with G-1
      (25 MUg) 48 h and 24 h prior to the information trial of a Y-maze task resulted
      in a greater preference for the arm associated with the novel environment on the
      retention trial. Collectively, the results indicated that short-term treatment of
      ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial
      recognition memory, an effect that also occurred following short-term treatment
      with a low dose of estradiol.

PMID- 24445073
TI  - Effects of kappa opioid receptors on conditioned place aversion and social
      interaction in males and females.
AB  - The effects of kappa opioid receptors (KOR) on motivated behavior are well
      established based on studies in male rodents, but relatively little is known
      about the effects of KOR in females. We examined the effects of KOR activation on
      conditioned place aversion and social interaction in the California mouse
      (Peromyscus californicus). Important differences were observed in long-term
      (place aversion) and short-term (social interaction) effects. Females but not
      males treated with a 2.5 mg/kg dose of U50,488 formed a place aversion, whereas
      males but not females formed a place aversion at the 10 mg/kg dose. In contrast
      the short term effects of different doses of U50,488 on social interaction
      behavior were similar in males and females. Acute injection with 10 mg/kg of
      U50,488 (but not lower doses) reduced social interaction behavior in both males
      and females. The effects of U50,488 on phosphorylated extracellular signal
      regulated kinase (pERK) and p38 MAP kinase were cell type and region specific.
      Higher doses of U50,488 increased the number of pERK neurons in the ventrolateral
      bed nucleus of the stria terminals in males but not females, a nucleus implicated
      in male aggressive behavior. In contrast, both males and females treated with
      U50,488 had more activated p38 cells in the nucleus accumbens shell.
      Unexpectedly, cells expressing activated p38 co-expressed Iba-1, a widely used
      microglia marker. In summary we found strong sex differences in the effects of
      U50,488 on place aversion whereas the acute effects on U50,488 induced similar
      behavioral effects in males and females.

PMID- 24445075
TI  - [Procalcitonin and C-reactive protein as early indicators of postoperative intra
      abdominal infection after surgery for gastrointestinal cancer].
AB  - AIM: to evaluate the association between serum levels of procalcitonin and C
      reactive protein, on the first 3 postoperative days, and the appearance of
      postoperative intra-abdominal infection. METHOD: Prospective observational study
      including 67 patients operated on for colo-rectal, gastric and pancreatic cancer.
      Serum levels of procalcitonin and C-reactive protein were analyzed before surgery
      and daily until the third postoperative day. Values of procalcitonin (PCT) and C
      reactive protein (CRP) were recorded as well as their accuracy for detection of
      postoperative intra-abdominal infection (PIAI). RESULTS: The incidence of
      postoperative intra-abdominal infection was 13.4%. CRP serum levels at 72h, PCT
      serum levels at 24, 48 and 72h and the ratio between serum levels of CRP at
      72hours and serum levels of CRP at 48hours (CRP D3/CRP D2) were significantly
      associated with the appearance of postoperative intra-abdominal infection. The
      highest sensitivity corresponded to PCT at 72hours (88.9%); the highest
      specificity and positive predictive value corresponded to the ratio CRP D3/CRP D2
      (96.49% and 71.4%, respectively); the highest negative predictive value to
      procalcitonin at 72h and 24h. CONCLUSIONS: Serum levels of PCT are significantly
      associated with the appearance of postoperative intra-abdominal infection.
      Sensitivity and predictive positive values are low, but negative predictive value
      is high, even at 24h after surgery.

PMID- 24445076
TI  - Childbirth fear in Swedish fathers is associated with parental stress as well as
      poor physical and mental health.
AB  - OBJECTIVE: to compare self-rated health and perceived difficulties during
      pregnancy as well as antenatal attendance, birth experience and parental stress
      in fathers with and without childbirth related fear. DESIGN: a longitudinal
      regional survey. Data were collected by three questionnaires. SETTING: three
      hospitals in the middle-north part of Sweden. PARTICIPANTS: 1047 expectant
      fathers recruited in mid-pregnancy and followed up at two months and one year
      after birth. MEASUREMENTS: childbirth fear was assessed using the Fear of Birth
      Scale (FOBS). Self-rated physical and mental health and perceived difficulties
      were assessed in mid pregnancy. Two months after birth antenatal attendance, mode
      of birth and the birth experience were investigated. Parental stress was measured
      using the Swedish Parental Stress Questionnaire (SPSQ). Crude and adjusted odds
      ratios were calculated between expectant fathers who scored 50 and above
      (childbirth fear) and those that did not (no fear). FINDINGS: expectant fathers
      with childbirth related fear (13.6%) reported poorer physical (OR 1.8; 95% CI 1.2
      2.8) and mental (OR 3.0; 1.8-5.1) health than their non-fearful counterparts. The
      fearful fathers were more likely to perceive difficulties in pregnancy (OR 2.1;
      1.4-3.0), and the forthcoming birth (OR 4.3; 2.9-6.3) compared to fathers without
      childbirth fear. First-time fathers with fear attended fewer antenatal classes.
      Fathers with high fear reported higher mean scores in four of the five subscales
      of the SPSQ. Childbirth related fear was not associated with mode of birth or
      fathers' birth experience. KEY CONCLUSIONS: expectant fathers with childbirth
      related fear had poorer health, viewed the pregnancy, birth and the forthcoming
      parenthood with more difficulties. They were less often present during antenatal
      classes and had higher parental stress. IMPLICATIONS FOR PRACTICE: this study
      provides insight into the health of expectant fathers during pregnancy and
      highlights the importance of understanding how childbirth fear may affect
      expectant fathers in both the short and longer term.

PMID- 24445077
TI  - Australian women's perception of their preparation for and actual experience of a
      recent scheduled caesarean birth.
AB  - OBJECTIVE: to add to knowledge around women's perceptions of their preparation
      for and actual experience of a recent scheduled caesarean birth. DESIGN,
      PARTICIPANTS AND SETTING: a mixed method study incorporating a postal survey and
      one-on-one interviews was used. The survey provided feedback on resources to
      prepare women for their caesarean birth such as a positive birth class, DVD and
      birth plan. Women were also invited to participate in an interview to share
      perceptions of their preparation and actual birth experience. Participants
      attended the only public obstetric tertiary hospital in Western Australia and
      experienced their caesarean birth between August and December 2012 (n=256).
      Frequency distributions and univariate comparisons were employed for categorical
      data, whereas thematic analysis was undertaken with transcripts to extract common
      themes. FINDINGS: data reflect 46% (117 out of 256) of women returned a postal
      survey. The interview option was removed after three months of data collection,
      when 38 women were interviewed and data saturation was reached. Of the 61% (71 of
      117) who completed a birth plan, 59% (42 of 71) felt it was used to guide their
      care. Only 38% (44 of 117) were able to stay together with their (baby and
      partner) in recovery. Thematic analysis revealed a positive theme suggesting
      their experience 'couldn't have been 'better' with sub-themes: 'involved in
      care'; 'informed the whole way through'; 'magical for him to be near me' and
      'everything was done brilliantly'. Negative reflections centred around 'we were
      just a number' and included four sub-themes: 'no option'; 'still had questions';
      'separated from him and her' and 'none of it happened'. CONCLUSION:
      acknowledgement that a scheduled caesarean section is more than a surgical
      procedure, but a birth is paramount. For women to have a positive birth
      experience we must respect their wishes within their birth plan and embrace a
      family friendly model, where mothers, partners and babies can stay together.

PMID- 24445078
TI  - Sesame oil attenuates nutritional fibrosing steatohepatitis by modulating matrix
      metalloproteinases-2, 9 and PPAR-gamma.
AB  - Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It
      contains sesamin, sesamol, and sesamolin, all of which contribute to its improved
      liver function in various animal model studies. However, its effect on
      nutritional fibrosing steatohepatitis is unclear. We investigated therapeutic
      sesame oil on matrix metalloproteinases-2, 9 (MMP-2, 9) in nutritional fibrosing
      steatohepatitic mice. C57BL/6 J mice were fed with methionine-choline deficient
      (MCD) diet for 35 days to induce fibrosing steatohepatitis. Sesame oil was
      treated from 29-35th day. Body weight, steatosis, aspartate transaminase, alanine
      transaminase, peroxisome proliferator-activated receptor (PPAR)-gamma, alpha
      smooth muscle actin (alpha-SMA), MMP-2, 9, and tissue inhibitor of matrix
      metalloproteinases (TIMP)-1 were assessed after 35 days. All tested parameters
      except TIMP-1 and PPAR-gamma were higher in MCD fed mice than in normal control
      mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with
      steatosis, necrotic-inflammation, and fibrosis. In sesame-oil (4 ml)-treated
      mice, all tested parameters except TIMP-1, alpha-SMA, and PPAR-gamma were
      significantly attenuated compared with MCD fed mice. Sesame oil inhibited MMP-2,
      9 activities, but up-regulated TIMP-1 expression in MCD fed mice. In addition, a
      histological analysis of liver tissue samples showed that sesame oil provided
      significant protection against fibrosis. We conclude that therapeutic sesame oil
      protects against fibrosing steatohepatitis by inhibiting MMP-2, 9 activities, up
      regulating TIMP-1 expression, and PPAR-gamma. 

PMID- 24445079
TI  - Push-pull farming systems.
AB  - Farming systems for pest control, based on the stimulo-deterrent diversionary
      strategy or push-pull system, have become an important target for sustainable
      intensification of food production. A prominent example is push-pull developed in
      sub-Saharan Africa using a combination of companion plants delivering
      semiochemicals, as plant secondary metabolites, for smallholder farming cereal
      production, initially against lepidopterous stem borers. Opportunities are being
      developed for other regions and farming ecosystems. New semiochemical tools and
      delivery systems, including GM, are being incorporated to exploit further
      opportunities for mainstream arable farming systems. By delivering the push and
      pull effects as secondary metabolites, for example, (E)-4,8-dimethyl-1,3,7
      nonatriene repelling pests and attracting beneficial insects, problems of high
      volatility and instability are overcome and compounds are produced when and where
      required. 

PMID- 24445081
TI  - A test of the Lamendin method of age estimation in South African canines.
AB  - Age estimation in unknown adult skeletons remains a considerable problem in
      forensic anthropology. In 1992, Lamendin et al. published a non-destructive
      method of age estimation on single rooted teeth. With this method, periodontosis
      and root transparency are judged against root height, and these are then used in
      regression formulae to estimate age. The aim of this study was to test the
      accuracy of the Lamendin method on a large sample of canines of South Africans,
      and if necessary to adapt the formulae for this population. A sample of known
      sex, age and population group was used. This included 537 upper and lower canines
      from 498 skulls, and included black males, black females, white males and white
      females. The age of the individuals ranged from 20 to 90 years. The original
      formulae gave relatively poor results, and in an attempt to obtain better
      accuracy the formulae were adapted with the current data. Even after adaptation
      of the formulae, the highest correlation between estimated age and actual age
      remained low (R(2)=0.41), with mean errors ranging between 12 and 15 years.
      Periodontosis was better correlated with age than root transparency. The accuracy
      of the method was found to be much lower than what was originally published, but
      probably reflects biological reality and is on a par with other methods of adult
      age estimation. 

PMID- 24445080
TI  - Synaptic gene dysregulation within hippocampal CA1 pyramidal neurons in mild
      cognitive impairment.
AB  - Clinical neuropathologic studies suggest that the selective vulnerability of
      hippocampal CA1 pyramidal projection neurons plays a key role in the onset of
      cognitive impairment during the early phases of Alzheimer's disease (AD).
      Disruption of this neuronal population likely affects hippocampal pre- and
      postsynaptic efficacy underlying episodic memory circuits. Therefore, identifying
      perturbations in the expression of synaptic gene products within CA1 neurons
      prior to frank AD is crucial for the development of disease modifying therapies.
      Here we used custom-designed microarrays to examine progressive alterations in
      synaptic gene expression within CA1 neurons in cases harvested from the Rush
      Religious Orders Study who died with a clinical diagnosis of no cognitive
      impairment (NCI), mild cognitive impairment (MCI, a putative prodromal AD stage),
      or mild/moderate AD. Quantitative analysis revealed that 21 out of 28 different
      transcripts encoding regulators of synaptic function were significantly
      downregulated (1.4-1.8 fold) in CA1 neurons in MCI and AD compared to NCI,
      whereas synaptic transcript levels were not significantly different between MCI
      and AD. The downregulated transcripts encoded regulators of presynaptic vesicle
      trafficking, including synaptophysin and synaptogyrin, regulators of vesicle
      docking and fusion/release, such as synaptotagmin and syntaxin 1, and regulators
      of glutamatergic postsynaptic function, including PSD-95 and synaptopodin.
      Clinical pathologic correlation analysis revealed that downregulation of these
      synaptic markers was strongly associated with poorer antemortem cognitive status
      and postmortem AD pathological criteria such as Braak stage, NIA-Reagan, and
      CERAD diagnosis. In contrast to the widespread loss of synaptic gene expression
      observed in CA1 neurons in MCI, transcripts encoding beta-amyloid precursor
      protein (APP), APP family members, and regulators of APP metabolism were not
      differentially regulated in CA1 neurons across the clinical diagnostic groups.
      Taken together, these data suggest that CA1 synaptic gene dysregulation occurs
      early in the cascade of pathogenic molecular events prior to the onset of AD,
      which may form the basis for novel pharmacological treatment approaches for this
      dementing disorder. This article is part of a Special Issue entitled
      'Neurodegenerative Disorders'. 

PMID- 24445082
TI  - External validation of the "walking estimated limitation calculated by history"
      (WELCH) questionnaire in patients with claudication.
AB  - OBJECTIVE: To externally validate the recently proposed "Walking Estimated
      Limitation Calculated by History" (WELCH) questionnaire. METHODS: A prospective
      study was performed on 450 new patients referred to our laboratory for treadmill
      testing (constant load 3.2 km/h and 10% slope for 15 minutes and then incremental
      increases). Results are presented as mean +/- SD or median [25th-75th
      percentiles] or number (percentage). An ankle brachial index <0.90 defined the
      presence of peripheral artery disease (PAD). Typical "vascular-type claudication"
      is a lower-limb pain or discomfort that is absent at rest, appears at exercise,
      forces stopping, and disappears within 10 minutes of exercise stopping. The
      Spearman r coefficient of correlation between maximal walking time (MWT) on
      treadmill and WELCH scores was calculated for patients with (PAD+) or without
      (PAD-) PAD, and reporting typical vascular-type claudication (VTC+) or not (VTC
      ). RESULTS: The WELCH score was obtained in all included patients. The number (%)
      of patients with a WELCH score <25 was 37 (54%), 198 (65%), 14 (44%), and 18
      (38%), and the Spearman correlation coefficient between WELCH score and treadmill
      MWT was 0.588, 0.609, 0.581, and 0.591 in the VTC-/PAD+, VTC+/PAD+, VTC-/PAD-,
      and VTC+/PAD- groups respectively (all p < .001). In PAD+/VTC+ patients, the
      WELCH positive predictive value for the inability to walk for 5 minutes on the
      treadmill was 79%. CONCLUSION: The WELCH score correlates moderately with
      treadmill-walking capacity in patients with or without PAD, and with or without
      typical VTC. It appears to be a simple to complete and easily scored instrument
      to help clinicians standardise the subjective estimation of walking capacity in
      their patients.

PMID- 24445083
TI  - Reliability of laser Doppler flowmetry curve reading for measurement of toe and
      ankle pressures: intra- and inter-observer variation.
AB  - OBJECTIVES: To assess the intra- and inter-observer variation in laser Doppler
      flowmetry curve reading for measurement of toe and ankle pressures. METHODS: A
      prospective single blinded diagnostic accuracy study was conducted on 200
      patients with known or suspected peripheral arterial disease (PAD), with a total
      of 760 curve sets produced. The first curve reading for this study was performed
      by laboratory technologists blinded to clinical clues and previous readings at
      least 3 months after the primary data sampling. The pressure curves were later
      reassessed following another period of at least 3 months. Observer agreement in
      diagnostic classification according to TASC-II criteria was quantified using
      Cohen's kappa. Reliability was quantified using intra-class correlation
      coefficients, coefficients of variance, and Bland-Altman analysis. RESULTS: The
      overall agreement in diagnostic classification (PAD/not PAD) was 173/200 (87%)
      for intra-observer (kappa = .858) and 175/200 (88%) for inter-observer data
      (kappa = .787). Reliability analysis confirmed excellent correlation for both
      intra- and inter-observer data (ICC all >=.931). The coefficients of variance
      ranged from 2.27% to 6.44% for intra-observer and 2.39% to 8.42% for inter
      observer data. Subgroup analysis showed lower observer-variation for reading of
      toe pressures in patients with diabetes and/or chronic kidney disease than
      patients not diagnosed with these conditions. Bland-Altman plots showed higher
      variation in toe pressure readings than ankle pressure readings. CONCLUSIONS:
      This study shows substantial intra- and inter-observer agreement in diagnostic
      classification and reading of absolute pressures when using laboratory
      technologists as observers. The study emphasises that observer variation for
      curve reading is an important factor concerning the overall reproducibility of
      the method. Our data suggest diabetes and chronic kidney disease have an
      influence on toe pressure reproducibility.

PMID- 24445084
TI  - A randomised controlled trial of supervised exercise regimens and their impact on
      walking performance, skeletal muscle mass and calpain activity in patients with
      intermittent claudication.
AB  - OBJECTIVES: Supervised exercise training (SET) is recommended for patients with
      intermittent claudication (IC). The optimal exercise programme has not been
      identified, and the potential adverse effects of exercise on these patients
      warrant consideration. Calpain proteases have been linked with tissue atrophy
      following ischaemia-reperfusion injury. High calpain activity may therefore cause
      muscle wasting in claudicants undergoing SET, and skeletal muscle mass (SMM) is
      integral to healthy ageing. This study assesses the impact of (1) treadmill-based
      SET alone; and (2) treadmill-based SET combined with resistance training on pain
      free walking distance (PFWD), SMM, and calpain activity. METHODS: Thirty-five
      patients with IC were randomised to 12 weeks of treadmill only SET (group A), or
      combined treadmill and lower-limb resistance SET (group B). PFWD via a 6-minute
      walking test, SMM via dual energy X-ray absorptiometry, and calpain activity via
      biopsies of gastrocnemius muscles were analysed. RESULTS: Intention-to-treat
      analyses revealed PFWD improved within group A (160 m to 204 m, p = .03), but not
      group B (181 m to 188 m, p = .82). There was no between group difference (p =
      .42). Calpain activity increased within group A (1.62 * 10(5) fluorescent units
      [FU] to 2.21 * 10(5) FU, p = .05), but not group B. There was no between group
      difference (p = .09). SMM decreased within group A (-250 g, p = .11) and
      increased in group B (210 g, p = .38) (p = .10 between groups). Similar trends
      were evident for per protocol analyses, but, additionally, change in SMM was
      significantly different between groups (p = .04). CONCLUSIONS: Neither exercise
      regimen was superior in terms of walking performance. Further work is required to
      investigate the impact of the calpain system on SMM in claudicants undertaking
      SET.

PMID- 24445085
TI  - Displacement forces in iliac landing zones and stent graft interconnections in
      endovascular aortic repair: an experimental study.
AB  - OBJECTIVES: Stent graft migration influences the long-term durability of
      endovascular aortic repair. Flow-induced displacement forces acting on the
      attachment zones may contribute to migration. Proximal fixation of aortic stent
      grafts has been improved by using hooks, while distal fixation and stent graft
      interconnections depend on self-expansion forces only. We hypothesized that flow
      induced displacement forces would be significant at the distal end, and would
      correlate with graft movements. METHODS: As part of an experimental study, an
      iliac limb stent graft was inserted in a pulsatile flow model similar to aortic
      in vivo conditions, and fixed-mounted at its proximal and distal ends to strain
      gauge load cells. Peak displacement forces at both ends and pulsatile graft
      movement were recorded at different graft angulations (0-90 degrees ), perfusion
      pressures (145/80, 170/90, or 195/100 mmHg), and stroke frequencies (60-100
      b.p.m.). RESULTS: Flow-induced forces were of the same magnitude at the proximal
      and distal end of the stent graft (peak 1.8 N). Both the forces and graft
      movement increased with angulation and perfusion pressure, but not with stroke
      rate. Graft movement reached a maximum of 0.29 +/- 0.01 mm per stroke despite
      fixed ends. There were strong correlations between proximal and distal
      displacement forces (r = 0.97, p < .001), and between displacement forces and
      graft movement (r = 0.98, p < .001). CONCLUSIONS: Pulsatile flow through a
      tubular untapered stent graft causes forces of similar magnitude at both ends and
      induces pulsatile graft movements in its unsupported mid-section. Peak forces are
      close to those previously reported to be required to extract a stent graft. The
      forces and movements increase with increasing graft angulation and perfusion
      pressure. Improved anchoring of the distal end of stent grafts may be considered.

PMID- 24445086
TI  - Delay to carotid endarterectomy in patients with symptomatic carotid artery
      stenosis.
AB  - OBJECTIVE: In patients with recently symptomatic carotid artery stenosis,
      guidelines recommend carotid revascularization within 2 weeks of the index event.
      The "index event" may be defined as either the first or the most recent event.
      The delay between the index event and carotid endarterectomy (CEA) over a period
      of 6 years in a single centre was evaluated and the effect of defining the index
      event as either the first or the most recent event was assessed. DESIGN:
      Observational study. METHODS: 555 consecutive patients with symptomatic carotid
      stenosis >= 50% treated with CEA between 2007 and 2012 were assessed. In 2010,
      changes to the in-hospital process of care to reduce delays in referral and CEA
      were introduced. These changes included, for example, improving access to
      physicians, imaging, and operating rooms. The delay from symptoms to surgery was
      expressed in days. RESULTS: The median time between the first event and surgery
      was reduced from 53 days (interquartile range [IQR] 30-78) in 2007 to 21 days
      (IQR 12-45) in 2012, and between the most recent event and CEA from 45 days (IQR
      28-67) to 17 days (IQR 9-28). Patients referred directly by their general
      practitioner more often underwent CEA within 2 weeks than patients referred by
      specialists from other hospitals. Compared to patients with transient ischaemic
      attack or ocular symptoms, patients with ischaemic stroke more often underwent
      CEA within 2 weeks. CONCLUSIONS: A small change in the process of care
      significantly reduced the delay from the index event to CEA, but in 2012 it still
      exceeded 14 days in the majority of patients. The definition of the "index event"
      has a large impact on the total duration of delay, and should therefore be
      uniform across studies.

PMID- 24445087
TI  - Editor's choice--Use of disposable radiation-absorbing surgical drapes results in
      significant dose reduction during EVAR procedures.
AB  - OBJECTIVES: Because of the increasing number of interventional endovascular
      procedures with fluoroscopy and the corresponding high annual dose for
      interventionalists, additional dose-protecting measures are desirable. The
      purpose of this study was to evaluate the effect of disposable radiation
      absorbing surgical drapes in reducing scatter radiation exposure for
      interventionalists and supporting staff during an endovascular aneurysm repair
      (EVAR) procedure. MATERIALS: This was a randomized control trial in which 36 EVAR
      procedures were randomized between execution with and without disposable
      radiation-absorbing surgical drapes (Radpad: Worldwide Innovations &
      Technologies, Inc., Kansas City, US, type 5511A). Dosimetric measurements were
      performed on the interventionalist (hand and chest) and theatre nurse (chest)
      with and without the use of the drapes to obtain the dose reduction and effect on
      the annual dose caused by the drapes. RESULTS: Use of disposable radiation
      absorbing surgical drapes resulted in dose reductions of 49%, 55%, and 48%,
      respectively, measured on the hand and chest of the interventionalist and the
      chest of the theatre nurse. CONCLUSIONS: The use of disposable radiation
      absorbing surgical drapes significantly reduces scatter radiation exposure for
      both the interventionalist and the supporting staff during EVAR procedures.

PMID- 24445088
TI  - Postural response latencies are related to balance control during standing and
      walking in patients with multiple sclerosis.
AB  - OBJECTIVE: To understand and examine the relation between postural response
      latencies obtained during postural perturbations and representative measures of
      balance during standing (sway variables) and walking (trunk motion). DESIGN:
      Cross-sectional. SETTING: University medical center. PARTICIPANTS: Persons with
      multiple sclerosis (MS) (n=40) were compared with similar aged control subjects
      (n=20). There were 20 subjects with MS in the normal walking velocity group and
      20 subjects with MS who had slow walking velocity based on a timed 25-foot walk
      (T25FW) of <5 seconds. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Postural
      response latency, sway variables, trunk motion variables. RESULTS: We found that
      subjects with MS with both slow or normal walking velocities had significantly
      longer postural response latencies than the healthy control group. Postural
      response latency was not correlated with the T25FW. Postural response latency was
      significantly correlated with center of pressure sway variables during quiet
      standing (root mean square: rho=.334, P=.04; range: rho=.385, P=.017; mean
      velocity: rho=.337, P=.038; total sway area: rho=.393, P=.015). Postural response
      latency was also significantly correlated with motion of the trunk during walking
      (sagittal plane range of motion: rho=.316, P=.05; SD of transverse plane range of
      motion: rho=-.43, P=.006). CONCLUSIONS: These findings clearly indicate that slow
      postural responses to external perturbations in patients with MS contribute to
      disturbances in balance control during both standing and walking.

PMID- 24445089
TI  - Investigating the role of backward walking therapy in alleviating plantar
      pressure of patients with diabetic peripheral neuropathy.
AB  - OBJECTIVE: To investigate the effect of combination therapy of backward walking
      training and alpha-lipoic acid (ALA) treatment on the distribution of plantar
      pressure in patients with diabetic peripheral neuropathy (DPN). DESIGN: This
      study is a double-blinded, randomized controlled trial. The test group was
      treated with combination therapy of backward walking exercise and ALA (ALA for
      2wk, backward walking exercise for 12wk), and the control group only received ALA
      treatment. SETTING: Clinical and laboratory setting. PARTICIPANTS: Patients with
      DPN (N=60) were divided into the test group (n=30) or control group (n=30).
      INTERVENTIONS: Backward walking exercise with ALA treatment for the test group;
      lipoic acid treatment for the control group. MAIN OUTCOME MEASURE: Plantar
      pressure before and after treatment was tested and analyzed with the flatbed
      plantar pressure measurement system. RESULTS: After treatment, peak plantar
      pressure in the forefoot dropped for both the test and control groups; peak
      plantar pressure for the test group dropped significantly. Peak plantar pressure
      in the medial foot slightly increased for the test group, suggesting a more even
      distribution of plantar pressure in the test group after treatment. CONCLUSIONS:
      The combination therapy of ALA and backward walking proved to be more effective
      than ALA monotherapy. Backward walking also proved to have an ameliorating effect
      on balance ability and muscle strength of patients with DPN.

PMID- 24445090
TI  - Performance metrics for power wheelchairs: a pipe dream?
AB  - Power wheelchair (PWC) users depend on their equipment to reliably transport them
      throughout daily activities and allow them to participate fully in community
      life. However, as reported by Worobey and colleagues, PWCs frequently require
      repairs and cause users a variety of problems, which can range from annoying to
      catastrophic. These authors suggest that comparing the performance of individual
      PWC makes and models--a PWC Consumer Reports--might be helpful to inform users
      and others about the relative quality of different products. Although a
      comparative report is an appealing idea, we suggest that producing meaningful
      comparisons of specific PWCs, especially complex rehabilitation PWCs, confronts
      significant methodologic and practical hurdles. Challenges include dealing with
      small sample sizes for individual products, risk-adjusting outcomes to account
      for systematic differences in patterns of use, specifying meaningful outcome
      metrics, distinguishing the contributions of manufacturers and PWC suppliers to
      suboptimal performance, and disentangling the myriad components of complex
      rehabilitation PWCs, which often carry parts from multiple manufacturers. In any
      case, most users have little control over their PWC selections, with the policies
      of health insurers and other factors largely dictating equipment choices.
      Considering these various concerns, we argue that producing a valid and useful
      Consumer Reports for PWCs will be difficult and, at least for complex
      rehabilitation chairs, will be of limited value.

PMID- 24445091
TI  - Is there a need for MRI within 24 hours after CT-guided percutaneous
      thermoablation of the liver?
AB  - BACKGROUND: Radiofrequency (RFA) and microwave ablation (MWA) are established
      minimally invasive techniques for treatment of hepatic tumors. PURPOSE: To
      compare technical success and accuracy of hepatic thermoablation using computed
      tomography (CT) and magnetic resonance imaging (MRI) acquired 24 h after ablation
      with regard to evaluation of the post-interventional ablation zone and local
      tumor recurrence (LTR), and to assess whether additional MRI within 24 h is
      beneficial. MATERIAL AND METHODS: Thirty-two patients (23 men, 9 women; mean age,
      60 years) with 48 lesions were included in this retrospective study. CT was
      performed immediately and MRI was performed 24 h after ablation. Diameter and
      volume calculations of the ablation zone were compared (T-Test). Technical
      success and ablation margin distinction, shape, and configuration were evaluated
      (kappa-statistic). Local effectiveness was calculated based on follow-up imaging.
      Technical success and ablation margin features were correlated with LTR (log-rank
      test, Fisher's exact test). RESULTS: Ablation zone volumes were significantly
      higher with MRI compared to CT (P < 0.05; mean volume, 55.19 and 45.97 mL).
      Agreement between CT and MRI for technical success was good (kappa = 0.801) and
      for margin conspicuity fair (kappa = 0.289). LTR was 26.1% (mean follow-up, 11.7
      months). LTR showed no correlation with technical success or margin conspicuity.
      CONCLUSION: CT and MRI are suited for early evaluation of technical success after
      thermoablation. Within 24 h a significant increase of the ablation volume is
      observed, which has to be taken into account when interpreting immediate
      postprocedural imaging and treating lesions near critical structures. Additional
      MRI 24 h after ablation seems of limited value regarding prognosis of LTR,
      especially with regards to evaluation of ablation margin shape and conspicuity.

PMID- 24445092
TI  - Contrast-enhanced ultrasound using real-time contrast harmonic imaging in
      invasive breast cancer: comparison of enhancement dynamics with three different
      doses of contrast agent.
AB  - BACKGROUND: In the last few years new potential applications have been developed
      for contrast-enhanced ultrasound (CEUS) and the management of breast diseases,
      but there is still some debate concerning the optimal dose to evaluate breast
      lesions, especially as a diagnostic tool. PURPOSE: To compare different CEUS
      doses of injected contrast agent in order to establish an optimal dose for the
      diagnosis of invasive breast cancer. MATERIAL AND METHODS: In Group A we compared
      the bolus dose of 1.2 mL vs. 2.4 mL and in Group B we compared the bolus dose of
      2.4 mL vs. 4.8 mL (26 and 25 invasive carcinomas, respectively). CEUS was
      performed in real-time contrast harmonic imaging (CHI) using a L9-3 MHz probe.
      All examinations were recorded in a contrast side/side imaging mode loop for 120
      s. Wash-in and wash-out patterns of the contrast agent were analyzed with
      advanced US quantification software and kinetic curves were used for statistical
      analysis. RESULTS: In Group B (2.4 mL vs. 4.8 mL), more and stronger correlation
      was found among kinetic parameters (area under the curve, P < 0.00001; lognormal
      model parameters, MU, P = 0.0007 and sigma, P < 0.0001; mean transit time, P <
      0.0001; model-based wash-out ratios, W21m, P = 0.0002; W50m, P = 0.0001; time-to
      peak, P = 0.005) as compared to Group A (1.2 mL vs. 2.4 mL). CONCLUSION: The
      optimal way to evaluate kinetic features of invasive breast tumors using real
      time CEUS is with an injection of contrast agent of either 2.4 mL or 4.8 mL.

PMID- 24445093
TI  - Quantitative measurement to evaluate morphological changes of the corpus callosum
      in patients with subcortical ischemic vascular dementia.
AB  - BACKGROUND: Subcortical ischemic vascular dementia (SIVD) is a subtype of
      dementia associated with abnormalities in the subcortical white matter regions.
      Recent imaging techniques can be used to detect such abnormalities in vivo.
      PURPOSE: To examine morphological changes of the corpus callosum in patients with
      SIVD by using magnetic resonance imaging (MRI) and diffusion tensor imaging
      (DTI). MATERIAL AND METHODS: MRI was performed to explore changes of cerebral
      white matter, especially corpus callosum. Brain matter diffusivity was examined
      with DTI by measuring the fractional anisotropy (FA). Results of 30 patients
      diagnosed with SIVD and 30 healthy subjects were analyzed and compared. RESULTS:
      The thicknesses of the genu, the anterior third, middle, and posterior third of
      the body, and the splenium of the corpus callosum were smaller in SIVD patients
      compared to healthy controls (0.54 +/- 0.08 vs. 0.68 +/- 0.09 cm, P = 0.0011;
      0.27 +/- 0.06 vs. 0.38 +/- 0.07 cm, P = 0.002; 0.28 +/- 0.05 vs. 0.38 +/- 0.08
      cm, P = 0.009; 0.18 +/- 0.04 vs. 0.26 +/- 0.06 cm, P = 0.013; 0.54 +/- 0.07 vs.
      0.72 +/- 0.09 cm, P = 0.003, respectively). The FA values of the genu and
      splenium of the corpus callosum in patients with SIVD were decreased compared to
      healthy controls (0.664 +/- 0.042 vs. 0.778 +/- 0.041, P < 0.001; 0.691 +/- 0.038
      vs. 0.786 +/- 0.039, P = 0.001, respectively). CONCLUSION: Patients with SIVD
      exhibit corpus callosum atrophy and morphological changes, and these
      characteristics may be useful for diagnosis.

PMID- 24445094
TI  - Rotator cuff tears: correlation between geometric tear patterns on MRI and
      arthroscopy and pre- and postoperative clinical findings.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is considered to be the best non
      invasive procedure for the evaluation of rotator cuff (RC) tendon tears.
      Burkhart's classification is a geometric classification of full-thickness RC
      tears on MRI. PURPOSE: To correlate MRI and arthroscopic geometric full-thickness
      RC tears according to the Burkhart's classification with pre- and postoperative
      clinical findings. MATERIAL AND METHODS: Patients who underwent arthroscopic RC
      repair between 2006 and 2010 were retrospectively evaluated. Preoperative MRI and
      arthroscopic surgical reports were reviewed for tear geometry (Burkhart's) by
      three (1 radiologist, 2 surgeons) and two (surgeons) readers. MRIs were also
      evaluated for tear size and change of tear size in successive sagittal sections
      and for muscle mass and fatty infiltration. Clinical examinations were performed
      preoperatively and at least 12 months afterwards. Postoperative function
      questionnaires were filled in by the patients. RESULTS: Forty-six patients (35
      men, 11 women; mean age, 57 years; range, 41-72 years) were evaluated. Tears
      depicted on MRIs were classified as crescent in 11 patients (24%), longitudinal
      in three (6.5%), massive contracted in 29 (63%), and cuff arthropathy in three
      (6.5%). Muscle changes were noted almost exclusively in patients with massive
      tears and cuff arthropathy (16/32 patients, P = 0.013). MRIs and arthroscopic
      geometric classifications were in close agreement. Tear type did not correlate
      with pre- and postoperative physical examination or with postoperative clinical
      questionnaires scores. CONCLUSION: Geometric RC tear characterizations on
      preoperative MRIs were closely associated with arthroscopic findings.
      Postoperative results were not affected by the geometric pattern of the tears.

PMID- 24445095
TI  - The changing world of family medicine: the new view from Cheyenne Mountain.

PMID- 24445096
TI  - Unresolved intergenerational issues.

PMID- 24445097
TI  - The voice of the new generation of family physicians.

PMID- 24445098
TI  - Practice facilitation to improve diabetes care in primary care: a report from the
      EPIC randomized clinical trial.
AB  - PURPOSE: We investigated 3 approaches for implementing the Chronic Care Model to
      improve diabetes care: (1) practice facilitation over 6 months using a reflective
      adaptive process (RAP) approach; (2) practice facilitation for up to 18 months
      using a continuous quality improvement (CQI) approach; and (3) providing self
      directed (SD) practices with model information and resources, without
      facilitation. METHODS: We conducted a cluster-randomized trial, called Enhancing
      Practice, Improving Care (EPIC), that compared these approaches among 40 small to
      midsized primary care practices. At baseline and 9 months and 18 months after
      enrollment, we assessed practice diabetes quality measures from chart audits and
      Practice Culture Assessment scores from clinician and staff surveys. RESULTS:
      Although measures of the quality of diabetes care improved in all 3 groups (all P
      <.05), improvement was greater in CQI practices compared with both SD practices
      (P <.0001) and RAP practices (P <.0001); additionally, improvement was greater in
      SD practices compared with RAP practices (P <.05). In RAP practices, Change
      Culture scores showed a trend toward improvement at 9 months (P = .07) but
      decreased below baseline at 18 months (P <.05), while Work Culture scores
      decreased from 9 to 18 months (P <.05). Both scores were stable over time in SD
      and CQI practices. CONCLUSIONS: Traditional CQI interventions are effective at
      improving measures of the quality of diabetes care, but may not improve practice
      change and work culture. Short-term practice facilitation based on RAP principles
      produced less improvement in quality measures than CQI or SD interventions and
      also did not produce sustained improvements in practice culture.

PMID- 24445099
TI  - Family physicians' quality interventions and performance improvement through the
      ABFM diabetes performance in practice module.
AB  - PURPOSE: Practice performance assessment is the fourth requirement of Maintenance
      of Certification for Family Physicians (MC-FP). American Board of Family Medicine
      (ABFM) diplomates have many options for completing Part 4 requirements, including
      Web-based Performance in Practice Modules (PPMs) developed by the ABFM. Our
      objective was to describe the actions and outcomes of family physicians who
      completed the ABFM diabetes PPM. METHODS: We undertook a descriptive study of all
      diabetes PPMs completed by physicians in the 50 United States and Washington, DC,
      from 2005 to October 2012. Successful completion required quality measure
      abstraction from 10 patient charts before and after a plan-do-study-act cycle
      improvement effort. We used descriptive statistics to assess physician
      demographics and quality outcomes. RESULTS: Family physicians completed 7,924
      diabetes qualitative improvement modules. Their mean age was 48.2 years, they had
      practiced a mean of 13.8 years, and three-fourths lived in urban areas (76.9%).
      Nearly one-half selected diabetic foot examination or eye examination as their
      quality improvement measure. Performance on all quality measures improved.
      Significant improvement was seen in rates of hemoglobin A1c control (<7.0%; 57.4%
      to 61.3%), blood pressure control (<130/90 mm Hg; 53.3% to 56.3%), foot
      examinations (68.0% to 85.8%); and retina examinations (55.5% to 71.1%). The most
      common interventions were standing orders (51.6%) and patient education (37.1%).
      CONCLUSIONS: Family physicians participating in MC-FP implemented improvement
      projects and showed quality improvements in caring for patients with diabetes.
      Emphasis on quality of care by payers will increasingly require physicians to
      embrace quality measurement and improvement.

PMID- 24445100
TI  - Targeted melanoma prevention intervention: a cluster randomized controlled trial.
AB  - PURPOSE: Targeted interventions to reduce the risk and increase the early
      detection of melanoma have the potential to save lives. We aimed to assess the
      effect of such an intervention on patient prevention behavior. METHODS: We
      conducted a pilot clustered randomized controlled trial, comparing a targeted
      screening and education intervention with a conventional information-based
      campaign in 20 private surgeries in western France. In the intervention group, 10
      general practitioners identified patients at elevated risk for melanoma with a
      validated assessment tool, the Self-Assessment Melanoma Risk Score (SAMScore),
      examined their skin, and counseled them using information leaflets. In the
      control group, 10 general practitioners displayed a poster and the leaflets in
      their waiting room and examined patients' skin at their own discretion. The main
      outcome measures were sunbathing and skin self-examinations among patients at
      elevated risk, assessed 5 months later with a questionnaire. RESULTS: Analyses
      were based on 173 patients. Compared with control patients, intervention patients
      were more likely to remember the campaign (81.4% vs 50.0%, P = .0001) and to
      correctly identify their elevated risk of melanoma (71.1% vs 42.1%, P = .001).
      Furthermore, intervention patients had higher levels of prevention behaviors:
      they were less likely to sunbathe in the summer (24.7% vs 40.8%, P = .048) and
      more likely to have performed skin self-examinations in the past year (52.6% vs
      36.8%, P = .029). The intervention was not associated with any clear adverse
      effects, although there were trends whereby intervention patients were more
      likely to worry about melanoma and to consult their general practitioner again
      about the disease. CONCLUSIONS: The combination of use of the SAMScore and
      general practitioner examination and counseling during consultations is an
      efficient way to promote patient behaviors that may reduce melanoma risk.
      Extending the duration of follow-up and demonstrating an impact on morbidity and
      mortality remain major issues for further research.

PMID- 24445101
TI  - Managing expectations of antibiotics for upper respiratory tract infections: a
      qualitative study.
AB  - PURPOSE: Communication experts have suggested that it is good practice to ask
      patients' directly whether they expect to receive antibiotics as part of asking
      about the triad of ideas, concerns, and expectations for health care. Our aim was
      to explore the views and experiences of family physicians about using this
      strategy with their patients, focusing the interview on the problem of eliciting
      expectations of antibiotics as a possible treatment for upper respiratory tract
      infections. METHODS: We conducted a qualitative study using semistructured
      interviews with 20 family physicians in South Wales, United Kingdom, and
      performing thematic analysis. RESULTS: Family physicians assumed most patients or
      parents wanted antibiotics, as well as wanting to be "checked out" to make sure
      the illness was "nothing serious." Physicians said they did not ask direct
      questions about expectations, as that might lead to confrontation. They preferred
      to elicit expectations for antibiotics in an indirect manner, before performing a
      physical examination. The majority described reporting their findings of the
      examination as a "running commentary" so as to influence expectations and help
      avoid generating resistance to a soon-to-be-made-explicit plan not to prescribe
      antibiotics. The physicians used the running commentary to preserve and enhance
      the physician-patient relationship. CONCLUSIONS: Real-world family physicians use
      indirect methods to explore expectations for treatment and, on the basis of their
      physical examination, build an argument for reassuring the patient or parent. In
      contrast to proposed models in the communication literature, interventions to
      promote appropriate antibiotic prescribing might include a focus on training in
      communication skills that (1) integrates these indirect methods as part of
      building collaborative physician-patient relationships and (2) uses the running
      commentary of examination findings to facilitate participation in clinical
      decisions.

PMID- 24445102
TI  - Strategies for achieving whole-practice engagement and buy-in to the patient
      centered medical home.
AB  - PURPOSE: The current model of primary care in the United States limits
      physicians' ability to offer high-quality care. The patient-centered medical home
      (PCMH) shows promise in addressing provision of high-quality care, but achieving
      a PCMH practice model often requires comprehensive organizational change. Guided
      by Solberg's conceptual framework for practice improvement, which argues for
      shared prioritization of improvement and change, we describe strategies for
      obtaining organizational buy-in to and whole-staff engagement of PCMH
      transformation and practice improvement. METHODS: Semistructured interviews with
      136 individuals and 7 focus groups involving 48 individuals were conducted in 20
      small- to mid-sized medical practices in Pennsylvania during the first regional
      rollout of a statewide PCMH initiative. For this study, we analyzed interview
      transcripts, monthly narrative reports, and observer notes from site visits to
      identify discourse pertaining to organizational buy-in and strategies for
      securing buy-in from personnel. Using a consensual qualitative research approach,
      data were reduced, synthesized, and managed using qualitative data management and
      analysis software. RESULTS: We identified 13 distinct strategies used to obtain
      practice buy-in, reflecting 3 overarching lessons that facilitate practice buy
      in: (1) effective communication and internal PCMH campaigns, (2) effective
      resource utilization, and (3) creation of a team environment. CONCLUSION: Our
      study provides a list of strategies useful for facilitating PCMH transformation
      in primary care. These strategies can be investigated empirically in future
      research, used to guide medical practices undergoing or considering PCMH
      transformation, and used to inform health care policy makers. Our study findings
      also extend Solberg's conceptual framework for practice improvement to include
      buy-in as a necessary condition across all elements of the change process.

PMID- 24445103
TI  - Measuring capability for healthy diet and physical activity.
AB  - PURPOSE: Patterns of diet and physical activity, major drivers of morbidity and
      mortality, are contingent on people's feasible opportunities to pursue healthy
      behaviors. Our objective for this mixed methods study was to develop measures of
      feasible opportunities for diet and activity. METHODS: The Capability Approach
      framework for evaluating people's real freedoms to pursue their values guided the
      research. A community-based participatory model was applied to conduct focus
      groups of adults with obesity or diabetes mellitus from an economically
      disadvantaged Latino community. Focus group themes were developed into survey
      items that assess how individual circumstances and neighborhood contexts
      influence opportunities for diet and activity. The prevalence of different
      influences was explored in a sample of 300 patients from a primary care safety
      net clinic. Scales measuring different aspects of opportunity were created
      through principal components analysis. RESULTS: Availability, convenience,
      safety, cost of food, and activity resources interact with individual
      circumstances, such as illness, depression, family and nonfamily supports, and
      scope of personal agency, to shape practical opportunities. Multiple
      vulnerabilities in availability of resources and moderators of resource use
      commonly occur together, intensifying challenges and creating difficult trade
      offs. Only one-half of participants reported that physicians understood their
      difficulties pursuing activity, and just one-third for diet. CONCLUSIONS: Our
      results suggest that practical opportunities for healthy behavior can be measured
      as a primary target for clinical and public health assessment and intervention.
      The Capability Approach holds promise as a framework for developing interventions
      responsive to both personal and environmental determinants.

PMID- 24445104
TI  - Self-rated health and long-term prognosis of depression.
AB  - PURPOSE: Indicators of prognosis should be considered to fully inform clinical
      decision making in the treatment of depression. This study examines whether self
      rated health predicts long-term depression outcomes in primary care. METHODS: Our
      analysis was based on the first 5 years of a prospective 10-year cohort study
      underway since January 2005 conducted in 30 randomly selected Australian primary
      care practices. Participants were 789 adult patients with a history of depressive
      symptoms. Main outcome measures include risks, risk differences, and risk ratios
      of major depressive syndrome (MDS) on the Patient Health Questionnaire. RESULTS:
      Retention rates during the 5 years were 660 (84%), 586 (74%), 560 (71%), 533
      (68%), and 517 (66%). At baseline, MDS was present in 27% (95% CI, 23%-30%).
      Cross-sectional analysis of baseline data showed participants reporting poor or
      fair self-rated health had greater odds of chronic illness, MDS, and lower
      socioeconomic status than those reporting good to excellent self-rated health.
      For participants rating their health as poor to fair compared with those rating
      it good to excellent, risk ratios of MDS were 2.10 (95% CI, 1.60-2.76), 2.38 (95%
      CI, 1.77-3.20), 2.22 (95% CI, 1.70-2.89), 1.73 (95% CI, 1.30-2.28), and 2.15 (95%
      CI, 1.59-2.90) at 1, 2, 3, 4, and 5 years, after accounting for missing data
      using multiple imputation. After adjusting for age, sex, multimorbidity, and
      depression status and severity, self-rated health remained a predictor of MDS up
      to 5 years. CONCLUSIONS: Self-rated health offers family physicians an efficient
      and simple way to identify patients at risk of poor long-term depression outcomes
      and to inform therapeutic decision making.

PMID- 24445105
TI  - Systems and complexity thinking in the general practice literature: an
      integrative, historical narrative review.
AB  - PURPOSE: Over the past 7 decades, theories in the systems and complexity sciences
      have had a major influence on academic thinking and research. We assessed the
      impact of complexity science on general practice/family medicine. METHODS: We
      performed a historical integrative review using the following systematic search
      strategy: medical subject heading [humans] combined in turn with the terms
      complex adaptive systems, nonlinear dynamics, systems biology, and systems
      theory, limited to general practice/family medicine and published before December
      2010. A total of 16,242 articles were retrieved, of which 49 were published in
      general practice/family medicine journals. Hand searches and snowballing
      retrieved another 35. After a full-text review, we included 56 articles dealing
      specifically with systems sciences and general/family practice. RESULTS: General
      practice/family medicine engaged with the emerging systems and complexity
      theories in 4 stages. Before 1995, articles tended to explore common
      phenomenologic general practice/family medicine experiences. Between 1995 and
      2000, articles described the complex adaptive nature of this discipline. Those
      published between 2000 and 2005 focused on describing the system dynamics of
      medical practice. After 2005, articles increasingly applied the breadth of
      complex science theories to health care, health care reform, and the future of
      medicine. CONCLUSIONS: This historical review describes the development of
      general practice/family medicine in relation to complex adaptive systems
      theories, and shows how systems sciences more accurately reflect the discipline's
      philosophy and identity. Analysis suggests that general practice/family medicine
      first embraced systems theories through conscious reorganization of its
      boundaries and scope, before applying empirical tools. Future research should
      concentrate on applying nonlinear dynamics and empirical modeling to patient
      care, and to organizing and developing local practices, engaging in community
      development, and influencing health care reform.

PMID- 24445106
TI  - A view from Cheyenne Mountain: Generation III's perspective of Keystone III.
AB  - In October 2000 the family of family medicine convened the Keystone III
      conference at Cheyenne Mountain Resort. Keystone III participants included
      members of Generation I (entered practice before 1970), Generation II (entered
      1970-1990), and Generation III (entered after 1990). They represented a wide
      range of family physicians, from medical students to founders of the discipline,
      and from small-town solo practice to academic medicine. During the conference,
      the three generations worked together and separately thinking about the past,
      present, and future of family medicine, our roles in it, and how the
      understanding of a family physician and our discipline had and would continue to
      evolve. After the conference, the 10 Generation III members wrote the article
      published here, reflecting on our experiences as new physicians and physicians in
      training, and the similarities and differences between our experiences and those
      of physicians in Generations I and II. Key similarities included commitment to
      whole-person care, to a wide scope of practice, to community health, and to
      ongoing engagement with our discipline. Key differences included our
      understanding of availability, the need for work-life balance, the role of
      technology in the physician-patient relationship, and the perceptions of the
      relationship between medicine and a range of outside forces such as insurance and
      government. This article, presented with only minor edits, thus reflects
      accurately our perceptions in late 2000. The accompanying editorial reflects our
      current perspective. 

PMID- 24445107
TI  - AHRQ updates on primary care research: upcoming webinar on multiple chronic
      conditions.

PMID- 24445109
TI  - Pisacano leadership foundation names 2013 Pisacano scholars.

PMID- 24445108
TI  - Building more medical schools won't solve patient access issues.

PMID- 24445110
TI  - The four pillars for primary care physician workforce reform: a blueprint for
      future activity.

PMID- 24445112
TI  - Effects of seductive details evidenced by gaze duration.
AB  - According to a meta-analysis of empirical studies, seductive details such as
      emotionally interesting text segments and attention-grabbing pictures have
      significant negative effects on the reader's recall, reading comprehension, and
      learning of important textual information. This study investigates the negative
      effects of seductive details on recall of main ideas and reading comprehension by
      using an eye-tracking technique. In the experiment, a total of 56 undergraduate
      students read a block of expository text with seductive details, and the spatial
      and temporal distribution of attention was measured by gaze duration and recorded
      by an eye tracker. Then recall and reading comprehension tests were employed. Two
      multiple regression analyses were conducted to investigate the relationship
      between attention allocation and reading performance. The results indicate that
      increased attention to seductive sentences, not to seductive pictures, was a
      major determinant of poor performance in terms of both recall and reading
      comprehension, suggesting that increased attentional allocation to seductive
      sentences may hinder information retrieval and produce a less coherent mental
      representation of given text. 

PMID- 24445111
TI  - Comparison of the classically conditioned withdrawal reflex in cerebellar
      patients and healthy control subjects during stance: 2. Biomechanical
      characteristics.
AB  - This study addresses cerebellar involvement in classically conditioned
      nociceptive lower limb withdrawal reflexes in standing humans. A preceding study
      compared electromyographic activities in leg muscles of eight patients with
      cerebellar disease (CBL) and eight age-matched controls (CTRL). The present study
      extends and completes that investigation by recording biomechanical signals from
      a strain-gauge-equipped platform during paired auditory conditioning stimuli (CS)
      and unconditioned stimuli (US) trials and during US-alone trials. The withdrawal
      reflex performance-lifting the stimulated limb (decreasing the vertical force
      from that leg, i.e. 'unloading') and transferring body weight to the supporting
      limb (increasing the vertical force from that leg, i.e. 'loading')-was quantified
      by the corresponding forces exerted onto the platform. The force changes were not
      simultaneous but occurred as a sequence of multiple force peaks at different
      times depending on the specific limb task (loading or unloading). Motor learning,
      expressed by the occurrence of conditioned responses (CR), is characterized by
      this sequence beginning already within the CSUS window. Loading and unloading
      were delayed and prolonged in CBL, resulting in incomplete rebalancing during the
      analysis period. Trajectory loops of the center of vertical pressure-derived from
      vertical forces-were also incomplete in CBL within the recording period. However,
      exposing CBL to a CS resulted in motor improvement reflected by shortening the
      time of rebalancing and by optimizing the trajectory loop. In summary,
      associative responses in CBL are not absent although they are less frequent and
      of smaller amplitude than in CTRL. 

PMID- 24445113
TI  - Mind the gap: delayed manifestation of long-term object memory improvement by
      phosphodiesterase inhibitors.
AB  - We examined the temporal profile of pharmacologically enhanced episodic memory,
      using the object recognition task. Male Wistar rats were tested at different
      retention intervals ranging from 1 h to 24 h. The object discrimination
      performance of all groups (untreated, placebo, drug treatment) gradually
      decreased up to an interval (8 h). Interestingly, only after this 8 h interval
      the memory improving effects of vardenafil and rolipram started to emerge. This
      time-dependent memory performance shows similarities with the Kamin effect. The
      delayed manifestation of drug-enhanced memory suggests that two separate memory
      mechanisms are at play, a quick transient form of memory and a more stable memory
      form that requires several hours to develop. It is important to take this into
      account when testing treatments intended for long-term memory enhancement.

PMID- 24445114
TI  - Use of sodium lauroyl sarcosinate (sarkosyl) in viable real-time PCR for
      enumeration of Escherichia coli.
AB  - The cell membranes of inactivated Escherichia coli are not always permeable to
      propidium monoazide (PMA). This limits the use of PMA real-time PCR (PMA-qPCR)
      for quantification of DNA from only viable cells for enumeration of E. coli. The
      aim of this study was to develop PMA-qPCR procedures for E. coli with improved
      selectivity for viable cells. E. coli inactivated by incubation at 52 degrees C
      were treated with 12 detergents before PMA treatment, and DNA was quantified by
      real-time PCR. Treatment with each of the 12 detergents and PMA increased the
      cycle threshold (Ct) values for heat inactivated E. coli suspensions. The
      greatest increase, of 10.68 Ct was obtained with sarkosyl. Treatment with sodium
      deoxycholate (NaDC) increased the Ct value by 8.99 Ct. Treatment with sarkosyl or
      NaDC of 16 heat treated 5-strain cocktails of verotoxigenic E. coli (VTEC)
      increased the mean Ct values by 8.15 or 6.82 Ct, respectively. Those mean values
      were significantly (p<0.05) different. When used to enumerate viable E. coli in
      suspensions treated with lactic acid or in mixtures of viable E. coli and E. coli
      inactivated by peroxyacetic acid, the slopes relating the Ct values from sarkosyl
      treated samples to the numbers of viable E. coli were 2.24 and 2.47,
      respectively, with regression coefficient values >=0.85. The findings show that
      sarkosyl was more effective than NaDC for dissipation of PMA-barrier properties
      of membranes of inactivated E. coli cells. Viable E. coli in mixtures of viable
      E. coli and E. coli inactivated by heat, lactic acid or peroxyacetic acid could
      be reliably enumerated by sarkosyl PMA-qPCR. 

PMID- 24445115
TI  - An aptamer-based electrochemical biosensor for the detection of Salmonella.
AB  - Salmonella is one of the most common causes of food-associated disease. An
      electrochemical biosensor was developed for Salmonella detection using a
      Salmonella-specific recognition aptamer. The biosensor was based on a glassy
      carbon electrode modified with graphene oxide and gold nanoparticles. Then, the
      aptamer ssDNA sequence could be linked to the electrode. Each assembly step was
      accompanied by changes to the electrochemical parameters. After incubation of the
      modified electrode with Salmonella, the electrochemical properties between the
      electrode and the electrolyte changed accordingly. The electrochemical impedance
      spectrum was measured to quantify the Salmonella. The results revealed that, when
      more Salmonella were added to the reaction system, the current between the
      electrode and electrolyte decreased; in other words, the impendence gradually
      increased. A detection limit as low as 3 cfu/mL was obtained. This novel method
      is specific and fast, and it has the potential for real sample detection.

PMID- 24445116
TI  - Insight in adults with obsessive-compulsive disorder.
AB  - The present study examined the clinical correlates of insight among adults with
      obsessive-compulsive disorder (OCD). One hundred and thirty treatment-seeking
      adults with a primary diagnosis of OCD, aged 18 to 68 years (mean 31.4 years)
      participated. Measures of clinical severity, obsessive-compulsive symptom
      dimensions, anxiety symptoms, depressive symptoms, and ability to resist and
      control OCD symptoms were obtained. Results indicated that poor insight was
      positively related to greater OCD symptom severity and poorer ability to resist
      and control OCD symptoms; this pattern of associations held when insight was
      examined continuously and categorically (i.e., high versus low insight). Insight
      was generally not associated with other clinical characteristics, except for a
      relationship with mental neutralizing behaviors. Insight did not mediate the
      relationship between the ability to resist and control OCD symptoms and obsessive
      compulsive symptom severity. Overall, this study provides further information
      into the nature and role of insight in adults with OCD. 

PMID- 24445117
TI  - Self-reported quality of life and clinician-rated functioning in mood and anxiety
      disorders: relationships and neuropsychological correlates.
AB  - This study aimed to investigate 1) the relationship between subjective perception
      of quality of life (QoL) and clinician-rated levels of psychosocial functioning
      and 2) the relationship of these indicators with neuropsychological performances,
      in a sample of 117 subjects with mood and anxiety disorders hospitalized for a 4
      week psychiatric rehabilitation program. At the beginning of the hospitalization,
      QoL and clinician-rated functioning were respectively measured by the World
      Health Organization Quality of Life Assessment-Brief Form (WHOQOL-BREF) and the
      Global Assessment of Functioning (GAF) scale, and subjects were administered a
      neuropsychological battery evaluating verbal and visual memory, working memory,
      attention, visual-constructive ability, language fluency and comprehension. We
      did not find any association between WHOQOL-BREF and GAF scores and between
      cognitive impairment and lower QoL or clinician-rated functioning. Our results
      suggest that 1) the individuals' condition encompasses different dimensions that
      are not fully captured by using only clinician-rated or self-administered
      evaluations; 2) the GAF scale seems unable to indicate the cognitive impairments
      of our subjects and the WHOQOL-BREF does not appear to be influenced by these
      deficits. Overall, our findings suggest the need of simultaneously use of
      multiple assessment tools, including objective evaluations of functioning and
      different measures of QoL, in order to obtain a more complete clinical picture of
      the patients. This may allow to identify more specific targets of therapeutic
      interventions and more reliable measures of outcome. 

PMID- 24445118
TI  - Urban segregation and the US heroin market: a quantitative model of
      anthropological hypotheses from an inner-city drug market.
AB  - BACKGROUND: We hypothesize that the location of highly segregated Hispanic and in
      particular Puerto Rican neighborhoods can explain how Colombian-sourced heroin,
      which is associated with a large-scale decade long decline in heroin price and
      increase in purity, was able to enter and proliferate in the US. METHODS: Our
      multidisciplinary analysis quantitatively operationalizes participant-observation
      ethnographic hypotheses informed by social science theory addressing complex
      political economic, historical, cultural and social processes. First, we
      ethnographically document the intersection of structural forces shaping
      Philadelphia's hypersegregated Puerto Rican community as a regional epicenter of
      the US heroin market. Second, we estimate the relationship between segregation
      and: (a) the entry of Colombian heroin into the US, and (b) the retail price per
      pure gram of heroin in 21 Metropolitan Statistical Areas. RESULTS: Ethnographic
      evidence documents how poverty, historically-patterned antagonistic race
      relations, an interstitial socio-cultural political and geographic linkage to
      both Caribbean drug trafficking routes and the United States and kinship
      solidarities combine to position poor Puerto Rican neighborhoods as commercial
      distribution centers for high quality, low cost Colombian heroin. Quantitative
      analysis shows that heroin markets in cities with highly segregated Puerto Rican
      communities were more quickly saturated with Colombian-sourced heroin. The level
      of Hispanic segregation (specifically in cities with a high level of Puerto Rican
      segregation) had a significant negative association with heroin price from 1990
      to 2000. By contrast, there is no correlation between African-American
      segregation and Colombian-sourced heroin prevalence or price. CONCLUSION: Our
      iterative mixed methods dialogue allows for the development and testing of
      complex social science hypotheses and reduces the limitations specific to each
      method used in isolation. We build on prior research that assumes geographic
      proximity to source countries is the most important factor in determining illicit
      drug prices and purity, while we find more complex, potentially modifiable
      determinants of geographic variation in retail drug markets. We show that
      specific patterns of ethnic segregation, racism, poverty and the political
      economy of socio-cultural survival strategies combined to facilitate the entry of
      pure, inexpensive Colombian-sourced heroin.

PMID- 24445119
TI  - Neighbourhood structural characteristics and crack cocaine use: exploring the
      impact of perceived neighbourhood disorder on use among African Americans.
AB  - BACKGROUND: Crack cocaine use and associated negative social and health
      consequences remain a significant public health problem. Research that expands
      beyond the individual by considering the environmental context as a determinant
      of cocaine use is growing. The main objectives of this paper are to examine the
      effects of perceived neighbourhood disorder as an independent correlate of the
      frequency of recent crack cocaine use and whether its impact is mediated by use
      related practices and social context of use among an African American adult
      sample in Atlanta (GA). METHODS: Cross-sectional data were collected from 461
      respondents who were recruited through active and passive community outreach from
      70 disadvantaged urban neighbourhoods across Atlanta. Multivariable negative
      binomial regression was performed to assess the independent association of
      perceived neighbourhood disorder with crack cocaine use frequency and to explore
      potential mediation by use-related practices and social context of use. RESULTS:
      Perceived neighbourhood disorder did not remain statistically significant after
      accounting for use-related practices and social context of use. Involvement in
      drug distribution and having traded sex were associated with increases in
      frequency of drug use, while using in safer places and using alone were
      associated with decreases in frequency of use. CONCLUSION: The results show that
      perceived neighbourhood disorder is associated with frequency of crack cocaine
      use independently of socio-demographics. However, its significance was eliminated
      when controlling for use-related practices and the social context of use. Such
      practices and the social context of use may mediate the relationship between
      neighbourhood disorder and crack cocaine use. Future research is needed to more
      fully elucidate the links between individual and neighbourhood characteristics
      that are related to crack cocaine use and strategies to reduce use must consider
      the salience of use-related practices and the social context of use.

PMID- 24445120
TI  - Transdermal delivery of flurbiprofen from surfactant-based vesicles: particle
      characterization and the effect of water on in vitro transport.
AB  - Flurbiprofen loaded rigid and elastic vesicles comprising the bilayer-forming
      surfactant sucrose-ester laurate were prepared by the film rehydration and
      extrusion method. The charge-inducing agent sodium dodecyl sulfate, and the
      micelle-forming surfactants, sorbitan monolaurate, polyethylene glycol
      monolaurate, and polysorbate 20, were used to enhance elasticity. Vesicle
      formulations were evaluated for size, zeta potential, (1)H and (19)F nuclear
      magnetic resonance (NMR) spectra, and in vitro skin permeation across Yucatan
      micropig (YMP) skin. Vesicle formulations were stable for 2 weeks and their mean
      sizes were 95-135 nm. NMR spectroscopy showed that flurbiprofen molecular
      mobility was restricted by interaction with vesicle components because of
      entrapment in vesicle bilayers. Moreover, sorbitan monolaurate-containing
      vesicles strongly retained flurbiprofen molecules. After non-occlusive
      application to YMP skin, flurbiprofen transport from all vesicle formulations was
      superior to that of flurbiprofen alone and remarkably decreased after water
      vaporization. Polarization microscopy and small-angle X-ray diffraction analysis
      showed that the vesicle formulation was transferred to liquid crystalline state.
      Suppression of vesicle transition to the liquid crystalline state was observed
      with applications of both large quantities and diluted samples. The presence of
      water in the formulations was associated with maintenance of the vesicle
      structure and greater flurbiprofen transport across YMP skin.

PMID- 24445121
TI  - The effects of heat on skin barrier function and in vivo dermal absorption.
AB  - Enhanced delivery of ingredients across the stratum corneum (SC) is of great
      interest for improving the efficacy of topically applied formulations. Various
      methods for improving dermal penetration have been reported including galvanic
      devices and micro-needles. From a safety perspective it is important that such
      approaches do not compromise SC barrier function. This study investigates the
      influence of topically applied heat in vivo on the dermal uptake and penetration
      of a model active, allantoin from gel and lotion formulations. A custom designed
      device was used to deliver 42 degrees C for 30s daily to human subjects after
      application of two formulations containing allantoin. The results were compared
      with sites treated with formulations containing no active and no heat, and a
      control site. In addition to penetration of allantoin, the integrity of the SC
      was monitored using trans-epidermal water loss (TEWL) measurements. The results
      showed that just 30s of 42 degrees C topically applied heat was enough to cause
      significantly more penetration of allantoin from the lotion formulation compared
      with no application of heat. TEWL data indicated that the integrity of the skin
      was not compromised by the treatment. However, the application of heat did not
      promote enhanced penetration of the active from the gel formulation. Vehicle
      composition is therefore an important factor when considering thermal enhancement
      strategies for targeting actives to the skin.

PMID- 24445122
TI  - Effects of C358A polymorphism of the endocannabinoid degrading enzyme fatty acid
      amide hydrolase (FAAH) on weight loss, adipocytokines levels, and insulin
      resistance after a high polyunsaturated fat diet in obese patients.
AB  - BACKGROUND AND AIMS: The C385A polymorphism of FAAH gene (rs324420C>A) has been
      associated with obesity. We investigate the role of this polymorphism on
      anthropometric and insulin resistance responses to a high polyunsaturated fat
      hypocaloric diet. METHODS: Obese individuals (no.=99) were assessed at baseline
      and after 3 months of a high polyunsaturated fat hypocaloric diet. RESULTS:
      Seventy-one patients (71.7%) had the genotype C385C and 28 (28.3%) patients had
      the C385A (26 patients, 26.3%) or A358A (2 patients, 2.0%) (A allele carriers
      group) genotype. In A allele carriers and after dietary intervention, total
      cholesterol (-16.3 +/- 37.4 mg/dl) and LDL-cholesterol (-12.9 +/- 6.5 mg/dl)
      levels decreased. In subjects with C385C genotype, the decreases were significant
      in total cholesterol (-12.3 +/- 27.4 mg/dl), LDL-cholesterol (-7.5 +/- 20.5
      mg/dl), insulin (-2.2 +/- 6.2 mUI/l), and homeostasis model assessment of insulin
      resistance (HOMA-R) (-0.79 +/- 1.15 units) levels. The weight loss was similar in
      both genotype groups (-4.1 +/- 3.8 kg vs -4.2 +/- 3.2 kg). Only leptin levels had
      a significant similar decrease in both genotypes. CONCLUSION: Subjects with C385C
      genotype of the FAAH showed an improvement on insulin and HOMA-R levels with a
      high polyunsaturated fat hypocaloric diet after weight loss during 3 months.

PMID- 24445123
TI  - Risk factors of sexual dysfunction after transurethral resection of the prostate
      (TURP): a 12 months follow-up.
AB  - The aim of this study was to evaluate the impact of risk factors of erectile
      dysfunction (ED) after transurethral resection of the prostate (TURP) in men with
      lower urinary tract symptoms caused by bladder outlet obstruction secondary to
      benign prostatic hyperplasia. The study was conducted prospectively on 178
      consecutive patients (normal IIEF-5 before surgery, >= 22) who underwent TURP.
      Patients were assessed before surgery and at 12 months. At 12 months, the IIEF-5
      score significantly decreased from24 to 18 (p<0.0001). No statistical
      associations were found between hypertension, diabetes, dyslipidemia and capsular
      perforation and the development of ED after TURP. Operating time, duration of
      catheterization, and BMI did not determine a significant decrease of the IIEF-5
      score after TURP. On univariable and multivariable linear regression analysis,
      age was the only risk factor associated with newly-reported ED 12 months after
      TURP (p<0.0001). On univariable andmultivariable logistic regression analysis,
      patients older than 65 yr had an higher risk of developing ED after TURP
      (p<0.0001) and they developed a lower IIEF-5 score (p<0.0001) at followup when
      compared with those <= 65 yr. These results suggest that age of patients
      represents an independent risk factor of ED at 12 months follow-up after TURP.

PMID- 24445124
TI  - Industrial endocrine disruptors and polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex and enigmatic syndrome of unknown
      origin and etiology enclosing a broad spectrum of phenotypic manifestations. PCOS
      pathophysiology combines reproductive and metabolic abnormalities into a
      heterogeneous disorder that has pervasive and devastating health consequences.
      Inquiring the generative roots of the syndrome, it has become increasingly
      apparent the role of the environment as a determinant factor. Experimental
      exposure to industrial endocrine disruptors has been related with the impairment
      of normal reproductive function and metabolic regulation possibly favoring the
      development of or aggravating PCOS-resembling clinical disorders. Industrial
      chemicals may reflect the contributing role of an unfavorable environment to
      unveil PCOS characteristics in genetically predisposed individuals or further
      deteriorate the hormonal and fertility imbalances of PCOS-affected females. 

PMID- 24445125
TI  - Use of parathyroid hormone in hypoparathyroidism.
AB  - Hypoparathyroidism is a disorder characterized by hypocalcemia, deficient PTH,
      and abnormal bone remodeling. Standard treatment of hypoparathyroidism consists
      of oral calcium and vitamin D supplementation. However, maintaining serum calcium
      levels can be a challenge. In addition, concerns exist regarding hypercalciuria
      and ectopic calcifications that can be associated with such treatment.
      Hypoparathyroidism is the only classic endocrine deficiency disease for which the
      missing hormone, PTH, is not yet an approved treatment. This review focuses on
      the use of PTH in the treatment of hypoparathyroidism, in the form of
      teriparatide [PTH(1-34)] and the full-length molecule, PTH(1-84). Studies in
      hypoparathyroid subjects demonstrate that PTH(1-34) and PTH(1-84) lower or
      abolish supplemental calcium and vitamin D requirements as well as increase
      markers of bone turnover. Densitometric and histomorphometric studies in some
      subjects treated with PTH(1- 34) and PTH(1-84) show an improvement in bone
      remodeling dynamics and return of bone metabolism toward normal levels. Given the
      chronic nature of hypoparathyroidism, and the expectation that PTH will be used
      for extended periods of time in hypoparathyroidism, further studies are needed to
      determine the long-term safety of PTH therapy in this population. 

PMID- 24445126
TI  - Effects of supramalleolar osteotomies for ankle osteoarthritis on foot kinematics
      and lower leg muscle activation during walking.
AB  - BACKGROUND: Early stages of asymmetric ankle osteoarthritis can be treated by
      joint preserving supramalleolar osteotomies that surgically realign the ankle and
      unload degenerated cartilage. While studies have already shown pain relief and
      functional improvements, the effects on gait biomechanics are largely unknown.
      This study investigated patients' gait pattern after supramalleolar osteotomies
      by focusing on foot kinematics and lower leg muscle activation. METHODS: An
      instrumented three-dimensional gait analysis with simultaneous electromyography
      of gastrocnemius medialis and lateralis, soleus, peroneus longus, and tibialis
      anterior muscles was performed on 12 patients with ankle osteoarthritis, seven of
      which were followed up 12-18months postoperatively. Additionally, seven different
      long-term follow-up patients (8-9years postoperatively) and 15 healthy control
      subjects were measured. The waveforms of the foot kinematics and muscle
      activation were analyzed using principal component analysis. FINDINGS: Compared
      to healthy controls, principal component scores that affected the sagittal range
      of motion of the hindfoot and hallux were lower in all patient groups, while
      scores that affected the timing of the peaks in the sagittal forefoot motion were
      mainly altered in short-term follow-up patients. Lower principal component scores
      in patients with ankle osteoarthritis and short-term follow-up patients resulted
      in a less pronounced peak activation of gastrocnemius medialis and soleus.
      INTERPRETATION: Both postoperative patient groups showed similar adaptations in
      their gait pattern as those observed in patients with ankle osteoarthritis. These
      changes are probably related to the lower ankle mobility. However, the reduced
      mobility seems to affect the patients' well-being less than a painful joint.

PMID- 24445127
TI  - Additive modelling reveals spatiotemporal PCBs trends in marine sediments.
AB  - We developed generalised additive mixed models (GAMMs) to infer spatiotemporal
      trends of environmental PCB concentrations from an extensive dataset (n=1219) of
      PCB concentrations measured between 1991 and 2010 in sediments of the Belgian
      Coastal Zone (BCZ) and the Western Scheldt estuary. A GAMM with time,
      geographical zone, periodicity and the organic carbon - water partition
      coefficient as covariates explained 49% of the variability in the log transformed
      PCB sediment concentrations. The time trends unraveled two to threefold PCB
      concentration decreases in the BCZ during the last 20 years. However, in the
      Western Scheldt estuary, time trends were spatially heterogeneous and not
      significantly decreasing. These results demonstrate that international efforts to
      cut down emissions of PCBs have been effective to reduce concentrations in open
      water ecosystems like the BCZ but had little effect in the urbanised and
      industrialised area of the Scheldt estuary.

PMID- 24445128
TI  - Photoproduction of hydrogen peroxide in aqueous solution from model compounds for
      chromophoric dissolved organic matter (CDOM).
AB  - To explore whether quinone moieties are important in chromophoric dissolved
      organic matter (CDOM) photochemistry in natural waters, hydrogen peroxide (H2O2)
      production and associated optical property changes were measured in aqueous
      solutions irradiated with a Xenon lamp for CDOM model compounds (dihydroquinone,
      benzoquinone, anthraquinone, napthoquinone, ubiquinone, humic acid HA, fulvic
      acid FA). All compounds produced H2O2 with concentrations ranging from 15 to 500
      MUM. Production rates were higher for HA vs. FA (1.32 vs. 0.176 mM h(-1)); values
      ranged from 6.99 to 0.137 mM h(-1) for quinones. Apparent quantum yields (Theta
      app; measure of photochemical production efficiency) were higher for HA vs. FA
      (0.113 vs. 0.016) and ranged from 0.0018 to 0.083 for quinones. Dihydroquinone,
      the reduced form of benzoquinone, had a higher production rate and efficiency
      than its oxidized form. Post-irradiation, quinone compounds had absorption
      spectra similar to HA and FA and 3D-excitation-emission matrix fluorescence
      spectra (EEMs) with fluorescent peaks in regions associated with CDOM.

PMID- 24445129
TI  - Behavioral responses by grey seals (Halichoerus grypus) to high frequency sonar.
AB  - The use of high frequency sonar is now commonplace in the marine environment.
      Most marine mammals rely on sound to navigate, and for detecting prey, and there
      is the potential that the acoustic signals of sonar could cause behavioral
      responses. To investigate this, we carried out behavioral response tests with
      grey seals to two sonar systems (200 and 375 kHz systems). Results showed that
      both systems had significant effects on the seals behavior; when the 200 kHz
      sonar was active, seals spent significantly more time hauled out and, although
      seals remained swimming during operation of the 375 kHz sonar, they were
      distributed further from the sonar. The results show that although peak sonar
      frequencies may be above marine mammal hearing ranges, high levels of sound can
      be produced within their hearing ranges that elicit behavioral responses; this
      has clear implications for the widespread use of sonar in the marine environment.

PMID- 24445130
TI  - Pre-loss symptoms related to risk of complicated grief in caregivers of
      terminally ill cancer patients.
AB  - PURPOSE: A number of studies have underlined a 10-20% prevalence of complicated
      grief (CG) among caregivers of cancer patients. The study aimed at examining the
      relationship between pre-loss criteria for CG and post-loss diagnosis of CG and
      at evaluating the validity and factor structure of a predictive tool, the
      Inventory of Complicated Grief (ICG), in order to identify the risk of developing
      CG in a sample of Italian caregivers. METHODS: Sixty family members of terminally
      ill patients admitted to hospice and receiving a Palliative Prognostic Score
      (PaP) predictive 30 day survival time <30% completed the Pre-Death ICG (ICG-PL)
      (T0). Family members were met again 6 months after the death of their loved one
      (T1) and submitted to the interview for Complicated Grief (Post-loss interview
      PLI). RESULTS: Caseness for CG was shown in 18.3% of caregivers at T1. ICG-PL
      score (T0) were higher among those who developed CG at T1 than non-cases. A cut
      off score >=49 on the ICG-PL (AUC=0.98) maximized sensitivity (92%) and
      specificity (98%) on caseness at T1. Pre-loss criteria related to traumatic
      distress, separation distress and emotional symptoms in general were
      significantly related to a post-loss diagnosis of CG, while no effect was shown
      on duration of pre-loss distress. CONCLUSIONS: The use of short screening tools,
      like the ICG-PL, may help health care professionals to identify subjects at risk
      for CG.

PMID- 24445131
TI  - Cognitive emotion regulation in euthymic bipolar disorder.
AB  - BACKGROUND: Based on findings indicating increased stress reactivity and
      prolonged stress recovery in individuals with bipolar disorder (BD), it has been
      proposed that emotion regulation (ER) deficits lie at the core of this disorder.
      Recent studies show an increased use of maladaptive ER strategies and a decreased
      use of adaptive ER strategies in BD. Whether this pattern is merely a correlate
      of affective episodes or might be a stable characteristic of BD, however, remains
      to be explored. In addition, it is unclear whether these deficits in ER are
      specific to people with a history of BD. METHODS: We examined whether euthymic BD
      individuals differ from healthy controls (HC) and individuals with a history of
      Major Depressive Disorder (MDD) with respect to the cognitive ER strategies they
      habitually use (CERQ) in response to negative affect. The sample consisted of 42
      bipolar patients, 43 patients with MDD and 39 HC. RESULTS: Compared to HC,
      euthymic BD and MDD individuals reported increased use of rumination,
      catastrophizing, and self-blame alongside decreased use of positive reappraisal,
      and putting into perspective. No differences were found between BD and MDD
      groups. LIMITATIONS: These findings are based on self-reports reflecting the
      habitual use of ER-strategies. The use of more objective methods and the
      examination of the spontaneous use of ER-strategies in euthymic BD would be
      desirable. CONCLUSIONS: Deficits in the habitual use of ER strategies may
      characterize BD and MDD individuals even outside of an acute episode and thereby
      play a role in the recurrence of affective disorders.

PMID- 24445132
TI  - Psychometric validation of the Hopkins Symptom Checklist (SCL-90) subscales for
      depression, anxiety, and interpersonal sensitivity.
AB  - BACKGROUND: The psychometric validity of many subscales of the 90-item Hopkins
      Symptom Checklist (SCL-90) remains largely unknown. Therefore, the aim of the
      present study was to evaluate the psychometric properties of the "Hamilton
      subscales" for depression (SCL-D16), anxiety (SCL-A14), their 6-item core
      measures (SCL-D6 and SCL-A6), the anxiety symptom scale (SCL-ASS8) and the
      interpersonal sensitivity scale (IPS5). METHODS: The psychometric properties of
      the SCL-D16, SCL-A14, SCL-D6, SCL-A6, SCL-ASS8, and the IPS5 were evaluated based
      on SCL-90 ratings from 850 day patients from a Danish psychiatric day hospital.
      The factor structure of the SCL-D16 and the SCL-A14 was investigated by means of
      principal component analysis (PCA) and the unidimensionality of all scales was
      estimated by Mokken analysis. Finally, the discriminant validity of the scales,
      i.e. their ability to distinguish between patients with various diagnoses, was
      tested. RESULTS: The PCA of the SCL-D16 and the SCL-A14 separated the core
      depression items from the arousal items on the SCL-D16 and the psychic anxiety
      items from the somatic anxiety items on the SCL-A14. According to the Mokken
      analyses, only the SCL-D6, the SCL-ASS8 and the IPS5 were unidimensional.
      Interestingly, the same three scales displayed discriminant validity for
      depression, anxiety disorders and personality disorders, respectively.
      LIMITATIONS: The study is based on data from Denmark. This may limit the validity
      of the results. CONCLUSIONS: Three unidimensional SCL-90 subscales were
      identified. Using these scales it is possible to perform a psychometrically valid
      evaluation of psychiatric patients regarding the severity of depression (HAM-D6),
      specific anxiety (SCL-ASS8) and interpersonal sensitivity (IPS5).

PMID- 24445133
TI  - Frontal-insula gray matter deficits in first-episode medication-naive patients
      with major depressive disorder.
AB  - OBJECTIVE: This study is designed to investigate the gray matter volume (GMV)
      deficits in patients with first-episode medication-naive major depressive
      disorder (MDD). METHODS: We enrolled 38 patients with first-episode medication
      naive MDD and 27 controls in this project. Voxel-based morphometry was used to
      compare GMV differences between two groups. Besides, the relationship between GMV
      of patients and the severity of clinical symptoms was estimated to confirm the
      role of GMV deficits in clinical symptoms. The correlation between total GMV and
      illness duration was also performed to elucidate the impacts of untreated
      duration on the GMV. RESULTS: We found that first-episode medication-naive MDD
      patients had significant GMV deficits in bilateral superior frontal gyri, left
      middle frontal gyrus, left medial frontal gyrus and left insula. The GMV of
      patient group was negatively correlated with the severity of clinical symptoms
      and the illness duration. CONCLUSION: A pattern of GMV deficits in fronto-insula
      might represent the biomarker for first-episode medication-naive MDD.

PMID- 24445134
TI  - Olfaction as a marker for depression in humans.
AB  - BACKGROUND: Animal studies show a strong link between the loss of olfactory
      function and depressive behavior. We analyzed, whether olfactory function is a
      marker for depression in humans. If so, reduced olfactory function can be
      expected in depression that improves to level of normality after successful
      antidepressive treatment. METHODS: Twenty-seven female in-patients with
      depression were compared to 28 healthy age-matched women at the beginning and at
      the end of antidepressive therapy or at two visits, respectively. Olfactory
      function was assessed comprehensively including threshold, discrimination and
      identification testing, chemosensory event related potentials and olfactory
      functional magnetic resonance imaging. RESULTS: At the beginning of psychotherapy
      the patients exhibited reduced olfactory discrimination, prolonged latencies of
      the event-related potential and reduced activation in secondary olfactory
      structures (thalamus, insula, and left middle orbitofrontal). After therapy,
      patients improved significantly in all of the parameters and consequently the
      differences between control group and patients vanished. LIMITATIONS AND
      CONCLUSION: We conclude that olfaction is a marker for depression. However, the
      results are limited to a relatively selective sample of depressed women.

PMID- 24445135
TI  - Potential use of point shear wave elastography for the pancreas: a single center
      prospective study.
AB  - AIM: Clinical use of point shear wave elastography for the liver has been
      established, however, few studies demonstrated its usefulness for the pancreas. A
      prospective study was conducted to clarify its feasibility for the pancreas and
      its usefulness for the identification of high risk group for pancreatic cancer.
      PATIENTS AND METHODS: Consecutive eighty-five patients underwent point shear wave
      elastography for the pancreas. The success rate of shear wave velocity (SWV)
      measurement, that is the number of successful measurements over total 10
      measurements, was recorded. The SWV of the pancreas measured at non-tumorous area
      was compared between patients with and without pancreatic cancer. Factors
      associated with high SWV were determined by logistic regression model. RESULTS:
      Sixty patients were included, of these 18 had pancreatic cancer. The success rate
      of 100% was achieved at the head, the body and the tail of the pancreas in 80%,
      83%, and 68% of the patients, respectively. The success rate of >=80% was
      achieved in 100%, 100%, and 96% of the patients, respectively. Although mean SWV
      of the pancreas harboring pancreatic cancer tended to be higher compared with
      that of the pancreas without cancer (1.51 +/- 0.45 m/s vs 1.43 +/- 0.28 m/s),
      they did not reach statistical significance. Multivariate analysis showed that
      increased amount of alcohol intake was associated with high SWV. CONCLUSION: The
      SWV of the pancreas was measured with excellent success rate. However, tendency
      of higher SWV obtained from the pancreas harboring pancreatic cancer needed to be
      further investigated.

PMID- 24445136
TI  - Prevalence of intestinal parasites in shelter and hunting dogs in Catalonia,
      Northeastern Spain.
AB  - To compare the prevalence of intestinal parasites in shelter and hunting dogs in
      Catalonia, Northeastern Spain, fresh faecal samples from 81 shelter dogs and 88
      hunting dogs were collected and analysed by faecal flotation. The overall
      prevalence of intestinal parasites was 71.6% in each population. In the shelter
      dog group, 67.9% of dogs were positive for intestinal protozoa and 9.8% were
      positive for helminths. In the hunting dog group, 20.4% of dogs were positive for
      intestinal protozoa and 63.6% were positive for helminths. A subset of Giardia
      positive samples was evaluated by PCR; Giardia assemblages C or D were detected.
      These results suggest that comprehensive parasite control measures should be
      implemented in both shelter and hunting dogs in Catalonia. 

PMID- 24445137
TI  - Optimal proportion of studded tyres in traffic flow to prevent polishing of an
      icy road.
AB  - Studded tyres can significantly wear the road surface and increase particle
      emissions from the road surface, which has a negative impact on air quality in
      urban areas. However, road wear might have a positive aspect by roughening the
      road surface and thus preventing polishing. As a consequence, other vehicles than
      the ones using studded tyres might also benefit from the usage of studded tyres.
      The impact of the proportion of studded tyres in the traffic flow on the tyre-ice
      friction coefficient was studied with a fleet of real cars in a closed
      environment under strict procedural control. The results show that a proportion
      of 25-50% studded tyres in the traffic flow is enough to prevent ice from
      developing in a manner that is critically slippery for non-studded winter tyres.
      It was also observed that the visual appearance of the ice surface does not
      indicate if the ice has become more slippery or not. 

PMID- 24445138
TI  - Arrival-time judgments on multiple-lane streets: The failure to ignore irrelevant
      traffic.
AB  - How do road users decide whether or not they have enough time to cross a multiple
      lane street with multiple approaching vehicles? Temporal judgments have been
      investigated for single cars approaching an intersection; however, close to
      nothing is known about how street crossing decisions are being made when several
      vehicles are simultaneously approaching in two adjacent lanes. This task is
      relatively common in urban environments. We report two simulator experiments in
      which drivers had to judge whether it would be safe to initiate street crossing
      in such cases. Matching traffic gaps (i.e., the temporal separation between two
      consecutive vehicles) were presented either with cars approaching on a single
      lane or with cars approaching on two adjacent lanes, either from the same side
      (Experiment 1) or from the opposite sides (Experiment 2). The stimuli were
      designed such that only the shortest gap was decision-relevant. The results
      showed that when the two gaps were in sight simultaneously (Experiment 1), street
      crossing decisions were also influenced by the decision-irrelevant longer gap.
      Observers were more willing to cross the street when they had access to
      information about the irrelevant gap. However, when the two gaps could not be
      seen simultaneously but only sequentially (Experiment 2), only the shorter and
      relevant gap influenced the street-crossing decisions. The results are discussed
      within the framework of perceptual averaging processes, and practical
      implications for road safety are presented. 

PMID- 24445139
TI  - The relationship between visibility aid use and motor vehicle related injuries
      among bicyclists presenting to emergency departments.
AB  - BACKGROUND: Little is known about the effectiveness of visibility aids (VAs;
      e.g., reflectors, lights, fluorescent clothing) in reducing the risk of a
      bicyclist-motor-vehicle (MV) collision. PURPOSE: To determine if VAs reduce the
      risk of a bicyclist-MV collision. METHODS: Cases were bicyclists struck by a MV
      and assessed at Calgary and Edmonton, Alberta, Canada, emergency departments
      (EDs) from May 2008 to October 2010. Controls were bicyclists with non-MV
      injuries. Participants were interviewed about their personal and injury
      characteristics, including use of VAs. Injury information was collected from
      charts. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for
      VAs during daylight and dark conditions, and adjusted for confounders using
      logistic regression. Missing values were imputed using chained equations and
      adjusted OR estimates from the imputed data were calculated. RESULTS: There were
      2403 injured bicyclists including 278 cases. After adjusting for age, sex, type
      of bicycling (commuting vs. recreational) and bicyclist speed, white compared
      with black (OR 0.52; 95% CI 0.28, 0.95), and bicyclist self-reported light
      compared with dark coloured (OR 0.67; 95% CI 0.49, 0.92) upper body clothing
      reduced the odds of a MV collision during daylight. After imputing missing
      values, white compared with black (OR 0.57; 95% CI: 0.32, 0.99) and bicyclist
      self-reported light compared with dark coloured (OR 0.71; 95% CI 0.52, 0.97)
      upper body clothing remained protective against MV collision in daylight
      conditions. During dark conditions, crude estimates indicated that reflective
      clothing or other items, red/orange/yellow front upper body clothing compared
      with black, fluorescent clothing, headlights and tail lights were estimated to
      increase the odds of a MV collision. An imputed adjusted analysis revealed that
      red/orange/yellow front upper body clothing colour (OR 4.11; 95% CI 1.06, 15.99)
      and tail lights (OR 2.54; 95% CI: 1.06, 6.07) remained the only significant risk
      factors for MV collisions. One or more visibility aids reduced the odds of a
      bicyclist MV collision resulting in hospitalization. CONCLUSIONS: Bicyclist
      clothing choice may be important in reducing the risk of MV collision. The
      protective effect of visibility aids varies based on light conditions, and non
      bicyclist risk factors also need to be considered.

PMID- 24445140
TI  - MicroRNA-451 suppresses tumor cell growth by down-regulating IL6R gene
      expression.
AB  - The miR-451 was found to be frequently down-regulated in tumors, indicating that
      miR-451 could play an important role in carcinogenesis. This study uncovered the
      mechanism by which the miR-451 functions as a tumor suppressor. The target genes
      of miR-451 were determined using target gene prediction softwares. Then the miR
      451 mimics were introduced into RKO and Hela cells respectively. The
      proliferation and invasion of cells were monitored by MTT, cell cycle and in
      vitro extracellular matrix invasion assays. Also the angiogenesis of HUVEC cells
      transfected with miR-451 mimics was examined. Subsequently, IL6R, a predicted
      target gene of miR-451, was studied by real time PCR, Western blotting, and siRNA
      technologies. The mRNA and protein levels of IL6R gene were found to be down
      regulated in the RKO and Hela cells transfected with miR-451 mimics.
      Consequently, the cell proliferation was inhibited. Also, the invasion of RKO
      cells was suppressed. Furthermore, the angiogenesis of HUVEC cells transfected
      with miR-451 mimics was assayed and the decreased angiogenic ability was detected
      compared to the controls. All these results were validated by IL6R siRNA
      experiments. The IL6R gene is a target gene of miR-451. The miR-451 behaves as a
      tumor suppressor, probably by targeting the IL6R pathway. 

PMID- 24445141
TI  - Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and
      trends in New Zealand and Queensland, Australia.
AB  - BACKGROUND: Increases in the incidence of squamous cell oropharyngeal cancer
      (OPC) have been reported from some countries, but have not been assessed in
      Australia or New Zealand. This study examines trends for squamous cell OPC and
      squamous cell oral cavity cancer (OCC) in two similarly sized populations, New
      Zealand and Queensland, Australia. METHODS: Incidence data for 1982-2010 were
      obtained from the respective population-based cancer registries for squamous cell
      OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes
      (APCs) were assessed by joinpoint regression. RESULTS: The incidence rates of
      squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006
      have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends
      were greatest at ages 50-69 and followed more gradual increases previously. In
      females, rates increased by 2.1% per year in New Zealand from 1982, but by only
      0.9% (not significant) in Queensland. In contrast, incidence rates for OCC
      decreased by 1.2% per year in males in Queensland since 1982, but remained stable
      for females in Queensland and for both sexes in New Zealand. Overall, incidence
      rates for both OCC and OPC were substantially higher in Queensland than in New
      Zealand. In males in both areas, OPC incidence is now higher than that of OCC.
      CONCLUSIONS: Incidence rates of squamous cell OPC have increased rapidly in men,
      while rates of OCC have been stable or reducing, showing distinct etiologies.
      This has both clinical and public health importance, including implications for
      the extension of human papilloma virus (HPV) vaccination to males.

PMID- 24445142
TI  - 12th International Congress on Toxoplasmosis.

PMID- 24445143
TI  - IRF5 is a target of BCR-ABL kinase activity and reduces CML cell proliferation.
AB  - Interferon regulatory factor 5 (IRF5) modulates the expression of genes
      controlling cell growth and apoptosis. Previous findings have suggested a lack of
      IRF5 transcripts in both acute and chronic leukemias. However, to date, IRF5
      expression and function have not been investigated in chronic myeloid leukemia
      (CML). We report that IRF5 is expressed in CML cells, where it interacts with the
      BCR-ABL kinase that modulates its expression and induces its tyrosine
      phosphorylation. Tyrosine-phosphorylated IRF5 displayed reduced transcriptional
      activity that was partially restored by imatinib mesylate (IM). Interestingly, a
      mutant devoid of a BCR-ABL consensus site (IRF5(Y104F)) still presented
      significant tyrosine phosphorylation. This finding suggests that the oncoprotein
      phosphorylates additional tyrosine residues or induces downstream signaling
      pathways leading to further IRF5 phosphorylation. We also found that ectopic
      expression of IRF5 decreases the proliferation of CML cell lines by slowing their
      S-G2 transition, increasing the inhibition of BCR-ABL signaling and enhancing the
      lethality effect observed after treatment with IM, alpha-2-interferon and a DNA
      damaging agent. Furthermore, IRF5 overexpression successfully reduced the
      clonogenic ability of CML CD34-positive progenitors before and after exposure to
      the above-indicated cytotoxic stimuli. Our data identify IRF5 as a downstream
      target of the BCR-ABL kinase, suggesting that its biological inactivation
      contributes to leukemic transformation. 

PMID- 24445145
TI  - Ubiquitin-specific protease 2a stabilizes MDM4 and facilitates the p53-mediated
      intrinsic apoptotic pathway in glioblastoma.
AB  - The mouse double minute 4 (MDM4) oncoprotein may inhibit tumorigenesis by
      regulating the apoptotic mediator p53. Ubiquitin-specific protease 2a (USP2a) is
      a deubiquitinating enzyme that protects MDM4 against degradation, so USP2-MDM4
      interaction may be a key determinant of the malignant potential of human cancers.
      MDM4 and USP2a, as well as the MDM4-USP2a complex, were more highly expressed in
      glioblastoma multiforme tissue samples from patients with good prognosis compared
      with patients with poor prognosis. Analysis of the prognostic parameters
      indicated that MDM4 expression was positively correlated with an increased
      likelihood for survival. Compared with the poor prognosis patients, mitochondria
      from good prognosis glioma patients contained higher levels of both MDM4 and the
      proapoptotic protein p53Ser46(P). In U87MG glioma cell line, the overexpression
      of MDM4 enhanced ultraviolet (UV)-induced cytochrome c release and apoptosis. In
      contrast, MDM4 knockdown decreased mitochondrial p53Ser46(P) levels and rescued
      cells from UV-induced apoptosis. The expression of MDM4 and USP2a were positively
      correlated with each other. MDM4-USP2a complexes were found only in the
      cytoplasmic fraction, whereas the mitochondrial fraction contained MDM4
      p53Ser46(P) and MDM4-Bcl-2 complexes. Overexpression of USP2a increased p53 and
      p53Ser46(P) levels in the mitochondria, whereas simultaneous MDM4 knockdown
      completely reversed this effect. UV-induced apoptosis was reduced by USP2a
      knockdown but restored by the simultaneous overexpression of MDM4. This apoptotic
      response was reduced by knockdown of p53 but not p21. Our results suggest that
      USP2a binds to and stabilizes MDM4; thus in turn, it enhances the mitochondrial
      localization of p53 and promotes apoptosis in glioma cells.

PMID- 24445144
TI  - The FGFR/MEK/ERK/brachyury pathway is critical for chordoma cell growth and
      survival.
AB  - Recent evidence suggests that the expression of brachyury is necessary for
      chordoma growth. However, the mechanism associated with brachyury-regulated cell
      growth is poorly understood. Fibroblast growth factor (FGF), a regulator of
      brachyury expression in normal tissue, may also play an important role in
      chordoma pathophysiology. Using a panel of chordoma cell lines, we explored the
      role of FGF signaling and brachyury in cell growth and survival. Western blots
      showed that all chordoma cell lines expressed fibroblast growth factor receptor 2
      (FGFR2), FGFR3, mitogen-activated protein kinase kinase (MEK) and extracellular
      signal-regulated kinase (ERK), whereas no cell lines expressed FGFR1 and FGFR4.
      Results of enzyme-linked immunosorbent assay indicated that chordoma cells
      produced FGF2. Neutralization of FGF2 inhibited MEK/ERK phosphorylation,
      decreased brachyury expression and induced apoptosis while reducing cell growth.
      Activation of the FGFR/MEK/ERK/brachyury pathway by FGF2-initiated
      phosphorylation of FGFR substrate 2 (FRS2)-alpha (Tyr196) prevented apoptosis
      while promoting cell growth and epithelial-mesenchymal transition (EMT).
      Immunofluorescence staining showed that FGF2 promoted the translocation of
      phosphorylated ERK to the nucleus and increased brachyury expression. The
      selective inhibition of FGFR, MEK and ERK phosphorylation by PD173074, PD0325901
      and PD184352, respectively, decreased brachyury expression, induced apoptosis,
      and inhibited cell growth and EMT. Moreover, knockdown of brachyury by small
      hairpin RNA reduced FGF2 secretion, inhibited FGFR/MEK/ERK phosphorylation and
      blocked the effects of FGF2 on cell growth, apoptosis and EMT. Those findings
      highlight that FGFR/MEK/ERK/brachyury pathway coordinately regulates chordoma
      cell growth and survival and may represent a novel chemotherapeutic target for
      chordoma.

PMID- 24445146
TI  - Referential framework for transcranial anatomical correspondence for fNIRS based
      on manually traced sulci and gyri of an infant brain.
AB  - Functional near infrared spectroscopy (fNIRS), which is compact, portable, and
      tolerant of body movement, is suitable for monitoring infant brain functions.
      Nevertheless, fNIRS also poses a technical problem in that it cannot provide
      structural information. Supplementation with structural magnetic resonance images
      (MRI) is not always feasible for infants who undergo fNIRS measurement.
      Probabilistic registration methods using an MRI database instead of subjects' own
      MRIs are optimized for adult studies and offer only limited resources for infant
      studies. To overcome this, we used high-quality infant MRI data for a 12-month
      old infant and manually delineated segmented gyri from among the highly visible
      macroanatomies on the lateral cortical surface. These macroanatomical regions are
      primarily linked to the spherical coordinate system based on external cranial
      landmarks, and further to traditional 10-20-based head-surface positioning
      systems. While macroanatomical structures were generally comparable between adult
      and infant atlases, differences were found in the parietal lobe, which was
      positioned posteriorly at the vertex in the infant brain. The present study
      provides a referential framework for macroanatomical analyses in infant fNIRS
      studies. With this resource, multichannel fNIRS functional data could be analyzed
      in reference to macroanatomical structures through virtual and probabilistic
      registrations without acquiring subject-specific MRIs. 

PMID- 24445147
TI  - Capecitabine and streptozocin +/- cisplatin in advanced gastroenteropancreatic
      neuroendocrine tumours.
AB  - BACKGROUND: Cytotoxic chemotherapy is widely used for advanced, unresectable
      pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and
      the most commonly used regimen combines 5-fluorouracil with streptozocin. The
      NET01 trial was designed to investigate whether capecitabine combined with
      streptozocin was an acceptable regimen with or without adding cisplatin. METHODS:
      Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut
      or unknown primary site were randomised to receive three-weekly capecitabine
      (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2)
      intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously
      on day 1. The primary outcome measure was objective response. Secondary outcome
      measures included progression-free and overall survival, quality of life,
      toxicity and biochemical response. RESULTS: 86 (44 CapStrep, 42 CapStrepCis)
      patients were randomised. Best objective response rate was 12% (95% confidence
      interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis.
      Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The
      estimated median progression-free and overall survival were 10.2 and 26.7 months
      for CapStrep and 9.7 and 27.5 months for CapStrepCis. 44% of CapStrep and 68% of
      CapStrepCis patients experienced grade >=3 adverse events. INTERPRETATION: The
      efficacies of the novel CapStrep+/-Cis regimens were very similar. CapStrep was
      better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004
      005202-71 and ISRCTN: 35124268.

PMID- 24445148
TI  - Performance of formulae based estimates of glomerular filtration rate for
      carboplatin dosing in stage 1 seminoma.
AB  - BACKGROUND: Single cycle carboplatin, dosed by glomerular filtration rate (GFR),
      is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is
      essential for correct dosing. Isotopic methods remain the gold standard for the
      determination of GFR. Formulae to estimate GFR have improved the assessment of
      renal function in non-oncological settings. We assessed the utility of these
      formulae for carboplatin dosing. METHODS: We studied consecutive subjects
      receiving adjuvant carboplatin for stage 1 seminoma at our institution between
      2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA)
      measurement of GFR with carboplatin dose calculated using the Calvert formula.
      Theoretical carboplatin doses were calculated from estimated GFR using Chronic
      Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD)
      and Cockcroft-Gault (CG) formulae with additional correction for actual body
      surface area (BSA). Carboplatin doses calculated by formulae were compared with
      dose calculated by isotopic GFR; a difference <10% was considered acceptable.
      RESULTS: 115 patients were identified. Mean isotopic GFR was 96.9 ml/min/1.73
      m(2). CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to
      underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI
      formula, corrected for actual BSA, performed best; 45.9% of patients received
      within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%)
      by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of
      the 40.5% receiving an excess dose. CONCLUSIONS: Our data support further
      evaluation of the CKD-EPI formula in this patient population but clinically
      significant variances in carboplatin dosing occur using non-isotopic methods of
      GFR estimation. Isotopic determination of GFR should remain the recommended
      standard for carboplatin dosing when accuracy is essential.

PMID- 24445149
TI  - The layering of auditory experiences in driving experience-dependent subcortical
      plasticity.
AB  - In this review article, we focus on recent studies of experiential influences on
      brainstem function. Using these studies as scaffolding, we then lay the initial
      groundwork for the Layering Hypothesis, which explicates how experiences combine
      to shape subcortical auditory function. Our hypothesis builds on the idea that
      the subcortical auditory system reflects the collective auditory experiences of
      an individual, including interactions with sound that occurred in the distant
      past. Our goal for this article is to begin to shift the field away from
      examining the effect of single experiences to examining how different auditory
      experiences layer or superimpose on each other. This article is part of a Special
      Issue entitled <Annual Reviews 2014>. 

PMID- 24445150
TI  - Cervical cancer screening: on the way to a shift from cytology to full molecular
      screening.
AB  - Cytology-based nation-wide cervical screening has led to a substantial reduction
      of the incidence of cervical cancer in western countries. However, the
      sensitivity of cytology for the detection of high-grade precursor lesions or
      cervical cancer is limited; therefore, repeated testing is necessary to achieve
      program effectiveness. Additionally, adenocarcinomas and its precursors are often
      missed by cytology. Consequently, there is a need for a better screening test.
      The insight that infection with high-risk human papillomavirus (hrHPV) is the
      causal agent of cervical cancer and its precursors has led to the development of
      molecular tests for the detection of hrHPV. Strong evidence now supports the use
      of hrHPV testing in the prevention of cervical cancer. In this review, we will
      discuss the arguments in favor of, and concerns on aspects of implementation of
      hrHPV testing in primary cervical cancer screening, such as the age to start
      hrHPV-based screening, ways to increase screening attendance, requirements for
      candidate hrHPV tests to be used, and triage algorithms for screen-positive
      women. 

PMID- 24445151
TI  - Association between palliative case management and utilization of inpatient,
      intensive care unit, emergency department, and hospice in Medicaid beneficiaries.
AB  - Association between palliative case management (PCM) and the utilization of major
      health services during the last 30 days of life in Medicaid patients with cancer
      was assessed using retrospective cohort analysis. There were 132 PCM enrollees in
      the intervention group and 54 non-PCM enrollees in the comparison group. The
      intervention group had lower inpatient admission rate than that of the comparison
      group (56.8% vs 74.1%), lower ICU admission rate (12.9% vs 24.1%), longer mean
      hospice days (45.8 vs 31.1 days), and lower percentage of persons with death in
      hospital (24.2% vs 35.9%). No statistically significant differences were found in
      mean intensive care unit days (8.7 vs 9.7 days), treat-and-release emergency
      department visit rate (22.0% vs 16.7%), or hospice election rate (65.9% vs
      70.4%). Palliative case management may reduce hospitalization and increase
      hospice use in patients nearing death. 

PMID- 24445152
TI  - Introduction to the special issue on structural stigma and health.

PMID- 24445153
TI  - [Severe idiopathic scoliosis. Does the approach and the instruments used modify
      the results?].
AB  - OBJECTIVE: The aim of this work is to evaluate and compare the radiographic
      results and complications of the surgical treatment of adolescents with
      idiopathic scoliosis greater than 75 degrees, using a double approach (DA) or an
      isolated posterior approach with hybrid instruments (posterior hybrid [PH]), or
      with "all-pedicle screws" (posterior screws [PS]). MATERIAL AND METHOD: A
      retrospective review was performed on 69 patients with idiopathic scoliosis
      greater than 75 degrees , with a follow-up of more than 2 years, to analyze the
      flexibility of the curves, the correction obtained, and the complications
      depending on the type of surgery. The Kruskal-Wallis test for non-parametric
      variables was used for the statistical analysis. RESULTS: There were no
      statistically significant differences between the 3 patient groups in the pre
      surgical Cobb angle values (DA=89 degrees , PH=83 degrees , PS=83 degrees ), in
      the immediate post-surgical (DA=34 degrees , PH=33 degrees , PS=30 degrees ), nor
      at the end of follow-up (DA=36 degrees , PH=36 degrees , PS=33 degrees ) (P>.05).
      The percentage correction (DA=60%, PH=57%, PS=60%) was similar between groups
      (P>.05). The percentage of complications associated with the procedure was 20.8%
      in DA, 10% in PH and 20% in PS. Two patients in the PS group showed changes, with
      no neurological lesions, in the spinal cord monitoring, and one patient in the
      same group suffered a delayed and transient incomplete lesion. DISCUSSION AND
      CONCLUSIONS: No significant differences were observed in the correction of severe
      idiopathic scoliosis between patients operated using the double or isolated
      posterior approach, regardless of the type of instrumentation used.

PMID- 24445155
TI  - Exopolysaccharide-producing Bifidobacterium animalis subsp. lactis strains and
      their polymers elicit different responses on immune cells from blood and gut
      associated lymphoid tissue.
AB  - The effect of exopolysaccharide (EPS) producing bifidobacteria, and the EPS
      derived thereof, on the modulation of immune response was evaluated. Cells
      isolated from gut associated lymphoid tissue (GALT) and from peripheral blood
      mononuclear cells (PBMC) of naive rats were used. The proliferation and cytokine
      production of these immune cells in the presence of the three isogenic
      Bifidobacterium animalis subsp. lactis strains (A1, A1dOx and A1dOxR), as well as
      their purified polymers, were in vitro analysed. The cytokine pattern produced by
      immune cells isolated from GALT showed that most levels remained stable in the
      presence of the three strains or their corresponding polymers. However, in PBMC
      the UV-inactivated bacteria induced higher levels of the ratios IFNgamma/IL-17,
      TNFalpha/IL-10 and TNFalpha/TGFbeta, and no variation in the ratio IFNgamma/IL-4.
      Thus, B. animalis subsp. lactis strains were able to activate blood monocytes as
      well as T lymphocytes towards a mild inflammatory Th1 response. Furthermore, only
      the EPS-A1dOxR was able to stimulate a response in a similar way than its EPS
      producing bacterium. Our work supports the notion that some bifidobacterial EPS
      could play a role in mediating the dialog of these microorganisms with the immune
      system. In addition, this study emphasizes the effect that the origin of the
      immune cells has in results obtained; this could explain the great amount of
      contradiction found in literature about the immunomodulation capability of EPS
      from probiotic bacteria. 

PMID- 24445154
TI  - [Can epidemiological factors affect the 2-year outcomes after surgery for
      degenerative lumbar disease in terms of quality of life, disability and post
      surgical pain?].
AB  - PURPOSE: To evaluate the influence of epidemiological factors on the outcomes of
      surgery for degenerative lumbar disease in terms of quality of life, disability
      and chronic pain. MATERIAL AND METHOD: A total of 263 patients who received
      surgery for degenerative lumbar disease (2005-2008) were included in the study.
      The epidemiological data collected were age, gender, employment status, and co
      morbidity. The SF-36, Oswestry Disability Index (ODI), Core Outcomes Measures
      Index (COMI), and VAS score for lumbar and sciatic pain were measure before and 2
      years after surgery. The correlation between epidemiological data and
      questionnaire results, as well as any independent prognostic factors, were
      assessed in the data analysis. RESULTS: The mean age of the patients was 54.0
      years (22-86), and 131 were female (49.8%). There were 42 (16%) lost to follow
      up. Statistically significant correlations (P<.05) were observed between age,
      gender, co-morbidity, permanent sick leave, and pre-operative pain with changes
      in the ODI, COMI, physical and SF-36 mental scales, and lumbar and sciatic VAS.
      Linear regression analysis showed permanent sick leave and age as predictive
      factors of disability (beta=14.146; 95% CI: 9.09 - 29.58; P<.01 and beta=0.334;
      95% CI: 0.40 - 0.98, P<.05, respectively), and change in quality of life (beta=
      8.568; 95% CI: -14.88 - -2.26; p<.01 and beta=-0.228, IC 95% CI: -0.40 - -0.06,
      P<.05, respectively). CONCLUSION: Based on our findings, age and permanent sick
      leave have to be considered as negative epidemiologic predictive factors of the
      outcome of degenerative lumbar disease surgery.

PMID- 24445156
TI  - Profile of anaerobic bacteriology of middle ear aspirates in a developing
      country: does immunocompromise play a role?
AB  - OBJECTIVES: The study intends to report the profiles of anaerobic bacteria
      isolated and attempts to evaluate the impact of immunocompromised status of
      patients on the disease. STUDY DESIGN: A cross-sectional prospective study.
      SETTING: ENT clinic, University of Ilorin Teaching Hospital, Nigeria; a 450-bed
      tertiary health facility. SUBJECTS: 104 consecutive consenting participants with
      clinical evidence of CSOM >=12 weeks. METHODS: A hospital-based study conducted
      over a seven (7) month period. The middle ear aspirate was obtained with the aid
      of a micropipette and sent immediately for Microscopy, Culture and Sensitivity of
      both anaerobic and aerobic bacterial isolates. RESULTS: A total of 11 patients
      with chronically discharging ears, of the 104 studied had anaerobic bacteria
      cultured from their middle ear aspirates. Age ranged from 4 to 50 years with a
      male:female ratio of 1:1.8. A total of 32 isolates (11 anaerobic and 21 aerobic)
      were recovered. All anaerobic organisms were mixed and included both
      Peptostreptococcus and Bacteroides. Metronidazole had 100% sensitivity to gram
      negative and 62.5% to gram positive anaerobic organisms tested. Five (5) patients
      had immunocompromised states of 11 patients with anaerobic bacteria isolated in
      middle ear aspirates (group I), while 13 immunocompromised patients of the
      remaining 93 patients with no anaerobic bacteria isolated (group II). The
      proportion of anaerobic isolates in group I is higher (p < 0.05) than in group
      II. CONCLUSION: Immunocompromised state and age appear to play key role in
      presence of the anaerobic organisms recovered from the middle ear of the patients
      studied.

PMID- 24445157
TI  - Evaluation of nested polymerase chain reaction for the early detection of
      Leptospira spp. DNA in serum samples from patients with leptospirosis.
AB  - The aim of this study was to analyse the nested polymerase chain reaction (nested
      PCR) in human serum samples of patients with clinical manifestations of
      leptospirosis. The cases of leptospirosis were defined by the microagglutination
      test (MAT). The samples were collected in 2010. Of 1042 serum samples collected
      from 521 patients, 28 (5.4%) were considered positive cases of leptospirosis, and
      493 (94.6%) were negative. Twenty-three confirmed cases had no MAT-detectable
      antibodies in the acute sample (mean of 5.6 days after onset). Nested PCR was
      positive in 22/23 (95.7%) patients during the acute phase of the disease, with
      negative results by MAT. Nested PCR was negative in all convalescent serum
      samples with positive results by MAT. All negative cases of leptospirosis were
      negative by nested PCR. The nested PCR is an alternative diagnostic tool for
      early detection of leptospires in sera during the first 7 days of the disease. 

PMID- 24445159
TI  - Multiplex quantitative polymerase chain reaction assay for the identification and
      quantitation of major vaginal lactobacilli.
AB  - Lactobacilli play a key role in promoting vaginal health. Depletion of these
      bacteria is associated with bacterial vaginosis (BV), the most common vaginal
      disorder. Here we describe the development and laboratory validation of a novel
      single-tube multiplex TaqMan quantitative polymerase chain reaction (qPCR) assay
      for the identification and quantitative assessment of the four major vaginal
      Lactobacillus species: L. crispatus, L. jensenii, L. gasseri, and L. iners. The
      assay utility was evaluated by the analysis of lactobacilli in non-cultured
      clinical vaginal swab specimens collected from BV patients and healthy
      individuals. As confirmed by the assay, L. crispatus, L. jensenii, and to a
      lesser extent L. gasseri, are common in the vagina of healthy women, whereas L.
      iners dominance is associated with BV. The major assay limitation was
      preferential detection of dominant Lactobacillus species in samples with mixed
      lactobacilli resulting in lower sensitivity for minor species. The multiplex qPCR
      assay described here is an advance in the detection and quantitation of the major
      vaginal lactobacilli, potentially facilitating the molecular diagnosis of BV and
      post-therapy restoration of the vaginal microflora. 

PMID- 24445158
TI  - Ceftaroline activity against bacterial organisms isolated from acute bacterial
      skin and skin structure infections in United States medical centers (2009-2011).
AB  - Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a new
      cephalosporin with bactericidal activity against resistant Gram-positive
      organisms including methicillin-resistant Staphylococcus aureus (MRSA) and
      multidrug-resistant strains of Streptococcus pneumoniae, and commonly isolated
      Gram-negative organisms, including ceftriaxone-susceptible Enterobacteriaceae. We
      evaluated the in vitro activity of ceftaroline and selected comparator agents
      against bacterial isolates collected from patients with acute bacterial skin and
      skin structure infections (ABSSSIs) in the USA. A total of 6222 isolates were
      collected from 67 medical centers distributed across all nine USA census regions
      between 2009 and 2011 and tested for susceptibility by reference broth
      microdilution methods. Ceftaroline was very active against S. aureus (MIC50/90,
      0.5/1 MUg/mL; 99.6% susceptible), including MRSA (MIC50/90, 0.5/1 MUg/mL; 99.1%
      susceptible). Against beta-hemolytic streptococci, the activity of ceftaroline
      (MIC50/90, <=0.015/0.03 MUg/mL; 100.0% susceptible) was comparable to that of
      both penicillin (MIC50/90, <=0.06/<=0.06 MUg/mL; 100.0% susceptible) and
      ceftriaxone (MIC50/90, <=0.25/<=0.25 MUg/mL; 100.0% susceptible). Ceftaroline was
      also highly active against viridans group streptococci (MIC50/90, 0.03/0.06
      MUg/mL). Similar to ceftriaxone and ceftazidime, ceftaroline was active against
      wild-type strains of Escherichia coli (MIC50/90, 0.12/0.25 MUg/mL; 94.0%
      susceptible) and Klebsiella pneumoniae (MIC50/90, 0.12/0.25 MUg/mL; 96.8%
      susceptible); however, the ceftaroline activity was compromised among strains
      with an extended-spectrum beta-lactamase-phenotype (MIC50/90, >32/>32 MUg/mL for
      both E. coli and K. pneumoniae). In summary, ceftaroline showed potent activity
      against a large contemporary collection (6222) of bacterial isolates associated
      with ABSSSI in the USA. 

PMID- 24445160
TI  - A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of
      infancy.
AB  - Benign paroxysmal torticollis of infancy (BPTI) is a rare paroxysmal disorder
      characterized by recurrent episodes of head tilt and accompanying general
      symptoms which remit spontaneously. The rare association with gain-of-function
      CACNA1A mutations, similar to hemiplegic migraine, has been reported. We report
      here two new BPTI patients from the same family carrying a heterozygous mutation
      in the CACNA1A gene leading to the change p.Glu533Lys. Functional analysis
      revealed that this mutation induces a loss of channel function due to impaired
      gating by voltage and much lower current density. Our data suggest that BPTI, a
      periodic syndrome commonly considered a migraine precursor, constitutes an age
      specific manifestation of defective neuronal calcium channel activity. 

PMID- 24445161
TI  - Assessment of cardiac autonomic function in patients with Duchenne muscular
      dystrophy using short term heart rate variability measures.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular
      disorder frequently associated with progressive cardiac dysfunction, and is one
      of the common causes of death in these children. Early diagnostic markers of
      cardiac involvement might help in timely intervention. In this study we compared
      the short term HRV measures of DMD children with that of healthy subjects.
      METHOD: One hundred and twenty-four genetically confirmed boys with DMD and 50
      age matched controls were recruited. Error-free, electrocardiogram was recorded
      in all subjects at rest in the supine position. HRV parameters were computed in
      time and frequency domains. Time domain measures included standard deviation of
      NN interval (SDNN), and root of square mean of successive NN interval (RMSSD).
      Frequency domain consisted of total, low frequency and high frequency power
      values. Ratio of low frequency and high frequency power values (LF/HF) was
      determined using customized software. RESULTS: HRV parameters were significantly
      altered in DMD children as compared to healthy controls. Following parameters
      [mean (SD)] were reduced in DMD as compared to controls; RMSSD (in ms) [52.14
      (33.2) vs 64.64 (43.2); p = 0.038], High frequency component (nu) [38.77 (14.4)
      vs 48.02 (17.1); p = 0.001] suggesting a loss of vagal tone. In contrast, measure
      of sympathovagal balance LF/HF [1.18 (0.87) vs 0.89 (0.79); p = 0.020] was
      increased in DMD group. CONCLUSION: In this cross sectional study we have
      demonstrated alteration in autonomic tone in DMD. Loss of vagal tone and an
      increase in sympathetic tone were observed in DMD children. Further prospective
      studies are required to confirm the utility of these measures as predictors of
      adverse cardiac outcome in DMD.

PMID- 24445163
TI  - Genetic and environmental bases of the interplay between magical ideation and
      personality.
AB  - Sub-threshold psychotic symptoms are quite commonly present in general
      population. Among these, Magical Ideation (MI) has been proved to be a valid
      predictor of psychosis. However, the genetic and environmental influences on the
      interplay between MI and personality have not fully been explored. A total of 534
      adult twins from the population-based Italian Twin Register were assessed for MI
      using the MI Scale (MIS) and for personality with the temperament and character
      inventory (TCI). A Multivariate Cholesky model was applied with Mx statistical
      program. The best-fitting model showed that additive genetic and unshared
      environmental factors explain approximately the same proportion of variance in
      MI, whereas a less strong genetic influence on personality traits emerged.
      Relevant correlations between MI and specific personality traits (novelty
      seeking, cooperativeness, self-directedness, self-transcendence) were found,
      suggesting shared influences for MI and these traits. Both genetic and
      environmental factors explained these correlations, with genetic factors playing
      a predominant role. Moderate-to-substantial genetic effects on MI and personality
      were found. Shared genetic and environmental effects underlie the phenotypic
      correlation between MI (psychosis-proneness) and personality traits, i.e. self
      directedness (negative association) and self-transcendence (positive
      association), potentially representing predictive markers of psychosis liability
      related to schizotypy and personality. 

PMID- 24445164
TI  - Mood-congruent memory in depression - the influence of personal relevance and
      emotional context.
AB  - The investigation of veridical mood-congruent memory (MCM) in major depressive
      disorder (MDD) has been subject of many studies, whereas mood-congruent false
      memory has received comparatively little attention. The present study examined
      the influence of valence, personal relevance and the valence of the context of
      the learning material on true and false MCM in 20 inpatients with MDD and 20
      healthy controls. Sixty positive, negative, neutral or personally relevant nouns
      were either combined with a positive, negative or neutral adjective. Word pairs
      were presented to participants in a learning trial. In a recognition task,
      participants had to identify the previously studied word pairs. A MCM effect
      could not be found for hits. However, in exploratory analyses, word pairs
      containing personally relevant nouns were more rated towards old by the patient
      relative to the control group. Furthermore, depressed patients tended to rate
      items more towards old than controls when the words were presented in a negative
      new context. Results are in line with previous findings in depression research
      emphasizing the role of mood-congruent false memories for mood disorders. 

PMID- 24445162
TI  - Microglial dysfunction in brain aging and Alzheimer's disease.
AB  - Microglia, the immune cells of the central nervous system, have long been a
      subject of study in the Alzheimer's disease (AD) field due to their dramatic
      responses to the pathophysiology of the disease. With several large-scale genetic
      studies in the past year implicating microglial molecules in AD, the potential
      significance of these cells has become more prominent than ever before. As a
      disease that is tightly linked to aging, it is perhaps not entirely surprising
      that microglia of the AD brain share some phenotypes with aging microglia. Yet
      the relative impacts of both conditions on microglia are less frequently
      considered in concert. Furthermore, microglial "activation" and
      "neuroinflammation" are commonly analyzed in studies of neurodegeneration but are
      somewhat ill-defined concepts that in fact encompass multiple cellular processes.
      In this review, we have enumerated six distinct functions of microglia and
      discuss the specific effects of both aging and AD. By calling attention to the
      commonalities of these two states, we hope to inspire new approaches for
      dissecting microglial mechanisms. 

PMID- 24445165
TI  - Theory of mind and hypomanic traits in general population.
AB  - Theory of Mind (ToM) is the ability to assign a set of mental states to yourself
      and others. In bipolar disorders, alteration of social relationship can be
      explained by the impairment of the functioning of ToM. Deficit in ToM could be a
      trait marker of bipolar disorder and people in the general population with high
      hypomanic personality scores would be more likely to develop bipolar disorders.
      This study examined 298 participants. Measures of hypomanic personality were
      evaluated using the Hypomanic Personality Scale. ToM was explored using the Yoni
      task. Participants also completed the BDI-II. Forward multiple regressions were
      performed to examine the effect of components of the HPS on the total score in
      the ToM task. In the women's group, no subscales of the HPS were included in the
      model. Conversely, the analyses performed on men revealed that the mood vitality
      and excitement subscale was a significant predictor of ToM abilities. Our study
      is the first to show the impact of certain dimensions of hypomanic personality on
      performance in ToM in a male sample. This result supports the idea that deficits
      in ToM can be a trait marker of bipolar disorder in a healthy male population. 

PMID- 24445166
TI  - Health care reform and its impact on radiology practice.
AB  - CMS is testing a range of payment policy options, including pay for performance,
      bundled payments, and shared savings through accountable care organizations.
      Radiologists can anticipate that the basis for how they are paid by Medicare will
      change and that they will need to play a greater role than has been required of
      them in the traditional fee-for-service payment system to demonstrate that
      imaging studies are used safely and efficiently. 

PMID- 24445168
TI  - Effect of pressure on refolding of recombinant pentameric cholera toxin B.
AB  - The production of recombinant proteins is an essential tool for the expansion of
      modern biological research and biotechnology. The expression of heterologous
      proteins in Escherichia coli often results in an incomplete folding process that
      leads to the accumulation of inclusion bodies (IB), aggregates that hold a
      certain degree of native-like secondary structure. High hydrostatic pressure
      (HHP) impairs intermolecular hydrophobic and electrostatic interactions, leading
      to dissociation of aggregates under non-denaturing conditions and is therefore a
      useful tool to solubilize proteins for posterior refolding. Cholera toxin (CT) is
      composed of a non-toxic pentamer of B subunits (CTB), a useful adjuvant in
      vaccines, and a toxic subunit A (CTA). We studied the process of refolding of CTB
      using HHP. HHP was shown to be effective for dissociation of CTB monomers from
      IB. Posterior incubation at atmospheric pressure of concentrated CTB (1mg/ml) is
      necessary for the association of the monomers. Pentameric CTB was obtained when
      suspensions of CTB IB were compressed at 2.4kbar for 16h in the presence of Tween
      20 and incubated at 1bar for 120h. Soluble and biologically active pentameric CTB
      was obtained, with a yield of 213mg CTB/liter of culture. The experience gained
      in this study can be important to improve the refolding of proteins with
      quaternary structure. 

PMID- 24445167
TI  - A brain basis for musical hallucinations.
AB  - The physiological basis for musical hallucinations (MH) is not understood. One
      obstacle to understanding has been the lack of a method to manipulate the
      intensity of hallucination during the course of experiment. Residual inhibition,
      transient suppression of a phantom percept after the offset of a masking
      stimulus, has been used in the study of tinnitus. We report here a human subject
      whose MH were residually inhibited by short periods of music.
      Magnetoencephalography (MEG) allowed us to examine variation in the underlying
      oscillatory brain activity in different states. Source-space analysis capable of
      single-subject inference defined left-lateralised power increases, associated
      with stronger hallucinations, in the gamma band in left anterior superior
      temporal gyrus, and in the beta band in motor cortex and posteromedial cortex.
      The data indicate that these areas form a crucial network in the generation of
      MH, and are consistent with a model in which MH are generated by persistent
      reciprocal communication in a predictive coding hierarchy. 

PMID- 24445169
TI  - Transcriptional profiling of biomass degradation-related genes during Trichoderma
      reesei growth on different carbon sources.
AB  - To identify all the gene products involved in cellulosic biomass degradation, we
      employed RNA sequencing technology to perform a genome-wide comparison of gene
      expression during growth of Trichoderma reesei QM9414 on cellulose or glucose.
      Due to their important role in lignocellulose decomposition, we focused on
      CAZymes and other secreted proteins. In total, 122 CAZymes showed at least a two
      fold change in mRNA abundance, and 97 of those were highly induced by cellulose.
      Compared to the well-characterized cellulases and hemicellulases, a majority of
      the other upregulated CAZymes showed lower transcriptional levels. In addition,
      64 secreted proteins, including oxidoreductases, exhibited at least two-fold
      upregulation on cellulose medium. To better understand the potential roles of low
      abundance CAZymes in cellulose breakdown, we compared the expression patterns of
      25 glycoside hydrolase genes under different conditions via real-time PCR.
      Substantial differences for the 25 genes were observed for individual strains
      grown on different carbon sources, and between QM9414 and RUTC30 when grown on
      the same carbon source. Moreover, we identified 3 genes that are coregulated with
      known cellulases. Collectively, this study highlights a comprehensive
      transcriptional profile for biomass degradation-related proteins and provides a
      first step toward the identification of candidates to construct optimized enzyme
      cocktails. 

PMID- 24445170
TI  - A thiol functionalized cryogel as a solid phase for selective reduction of a
      cysteine residue in a recombinant human growth hormone variant.
AB  - Site selective chemical modification is a preferred method, employed to prolong
      the circulation half-life of biopharmaceuticals. Cysteines have been used as
      attachment point for such modification, however, to be susceptible for chemical
      modification the involved thiol must be in its reduced form. Proteins often
      contain disulfides, which aid to maintain their tertiary structure and therefore
      must remain intact. Thus, methods for selectively reducing cysteine residues,
      introduced through site-directed mutagenesis, are of interest. In this study a
      macroporous, polymeric monolith was designed for selectively reducing a single
      cysteine residue inserted in recombinant human growth hormone (hGH). Advantages
      of such a material are the circumvention of the need to remove the reducing agent
      after reaction, as well as milder reduction conditions and a concomitant lower
      risk of reducing the native disulfides. The designed monolith showed very high
      capacity towards the selective reduction of an unpaired cysteine residue in a
      recombinant hGH variant. Factors influencing the selectivity and rate of reaction
      were investigated and it was found that monolith thiol loading, and buffer pH had
      an effect on the rate of reduction, whereas hGH variant concentration and buffer
      conductivity influenced both rate of reduction and selectivity. The developed
      system constitutes the basis for the development of a scalable platform for
      selective reduction of a capped cysteine residue in hGH. 

PMID- 24445171
TI  - Bioleaching waste printed circuit boards by Acidithiobacillus ferrooxidans and
      its kinetics aspect.
AB  - In this paper, H(+) consumption and metal recovery, during the process of
      bioleaching waste printed circuit boards (WPCBs) by Acidithiobacillus
      ferrooxidans (A. ferrooxidans), were discussed in detail. When the WPCBs
      concentration was 15g/L, Cu (96.8%), Zn (83.8%), and Al (75.4%) were recovered
      after 72h by A. ferrooxidans. Experimental results indicated that metal recovery
      rate was significantly influenced by acid. Based on experimental results, the
      kinetics of the H(+) consumption and metal recovery on bioleaching WPCBs were
      represented by reaction kinetic equations. The kinetic of H(+) consumption could
      be described by the second-order kinetic model. The metal recovery belongs to the
      second-order model with adding acid, which was changed to the shrinking core
      model with precipitate production. 

PMID- 24445172
TI  - Characterization of tobermolite as a bed material for selective growth of
      methanotrophs in biofiltration.
AB  - Tobermolite was characterized as a bed material for methanotrophic biofiltration.
      A lab-scale biofilter packed with tobermolite was operated for different
      operation times under identical conditions. The three different runs showed
      similar acclimation patterns of methane oxidation, with methane removal
      efficiency increasing rapidly for the first few days and peaking within three
      weeks, after which the efficiency remained stable. The mean methane removal
      capacities ranged from 766gm(-3)d(-1) to 974gm(-3)d(-1) after acclimation.
      Pyrosequencing indicated that the methanotrophic proportion
      (methanotroph/bacteria) increased to 71-94% within three weeks. Type I
      methanotrophs Methylocaldum and Methylosarcina were dominant during the initial
      growth period, then Methylocaldum alone dominated the methanotrophic community. A
      community comparison showed that total bacterial and methanotrophic communities
      were temporally stable after the initial growth period. Quantitative PCR showed
      that methanotrophic density increased during the first 3-4 weeks, then remained
      stable over 120 days. Tobermolite can provide a special habitat for the selective
      growth of methanotrophs, resulting in rapid acclimation. Tobermolite also allows
      the microbial community and methanotrophic density to remain stable, resulting in
      stable methane biofiltration. 

PMID- 24445174
TI  - Growth performance of early-weaned pigs is enhanced by feeding epidermal growth
      factor-expressing Lactococcus lactis fermentation product.
AB  - We have previously generated epidermal growth factor expressing Lactococcus
      lactis (EGF-LL) using bioengineering approach, and shown that feeding newly
      weaned piglets EGF-LL improves digestive function. To address concerns over the
      use of genetically modified organisms (GMO), the objective of the current study
      was to investigate the effect of feeding the EGF-LL fermentation product, after
      removal of the genetically modified EGF-LL, on growth performance and intestine
      development of newly-weaned piglets. One hundred and twenty newly-weaned piglets
      were fed ad libitum according to a 2-phase feeding program. Four pens were
      assigned to each of three treatments: (1) complete EGF-LL fermentation product
      (Ferm), (2) supernatant of EGF-LL fermentation product, after removal of EGF-LL
      (Supern), or (3) blank M17GE media (Control). EGF-LL or its fermented supernatant
      was administrated to piglets in the first 3 weeks post-weaning; their growth
      performance was monitored throughout treatment, and for the following week. Daily
      body weight gain (254.8g vs. 200.5g) and Gain:Feed (0.541kg/kg vs. 0.454kg/kg) of
      pigs on the Supern group were significantly improved compared to that of Control,
      although no difference was observed between the Ferm and Control pigs. Intestinal
      sucrase activity was increased in Supern- compared to Control group (166.3+/-62.1
      vs. 81.4+/-56.5nmol glucose released/mg protein; P<0.05). The lack of growth
      response with Ferm pigs may be attributed to an overload of bacteria (daily dose
      included 4.56*10(10)CFU/kg BW/day EGF-LL). These results suggest that GMO-free
      EGF-LL fermentation product is effective in increasing growth performance of
      early-weaned piglets. 

PMID- 24445173
TI  - Optimization of eGFP expression using a modified baculovirus expression system.
AB  - The baculovirus gene expression system is an efficient and safe protein
      expression system, since baculoviruses cannot replicate in mammalian cells. In
      order to improve the transduction efficiency and increase the reporter gene
      expression levels delivered by baculoviruses, we tested in the baculovirus
      expression cassette the Woodchuck hepatitis virus response element (WPRE), and
      AAV-derived inverted terminal repeats (ITRs) and the truncated vesicular
      stomatitis virus G protein (VSV-GED). The results showed that WPRE and VSV-GED
      have synergistic effects and could enhance the expression efficiency of enhanced
      green fluorescence protein (eGFP), and that ITRs effectively extended the
      duration of eGFP expression. We also demonstrated that the efficiency of eGFP
      expression varied under the control of the CMV, CBA, EF1-alpha or WSSV ie1
      promoters in different cell lines. 

PMID- 24445175
TI  - Bortezomib-induced lung toxicity.

PMID- 24445176
TI  - Reply to the letter "care mechanisms to avoid readmission of patients with
      chronic obstructive pulmonar disease".

PMID- 24445177
TI  - Detection of an O-methyltransferase synthesising acetosyringone in methyl
      jasmonate-treated tobacco cell-suspensions cultures.
AB  - Acetosyringone (3',5'-dimethoxy-4'-hydroxyacetophenone) is a well-known and very
      effective inducer of the virulence genes of Agrobacterium tumefaciens but the
      precise pathway of its biosynthesis in plants is still unknown. We have used two
      tobacco cell lines, cultured in suspension and exhibiting different patterns of
      accumulation of acetosyringone in their culture medium upon treatment with methyl
      jasmonate, to study different steps of acetosyringone biosynthesis. In the two
      cell lines studied, treatment with 100 MUM methyl jasmonate triggered a rapid and
      transient increase in acetovanillone synthase activity followed by a progressive
      increase in S-adenosyl-L-methionine: 5-hydroxyacetovanillone 5-O
      methyltransferase activity which paralleled the rise in acetosyringone
      concentration in the culture medium. This O-methyltransferase displayed Michaelis
      Menten kinetics with an apparent Km value of 18 MUM for 5-hydroxyacetovanillone
      and its activity was magnesium-independent. Its molecular mass was estimated by
      gel permeation on an FPLC column and was found to be of ca. 81 kDa. 5
      Hydroxyacetovanillone was the best substrate among the different o-diphenolic
      compounds tested as methyl acceptors in the O-methyltransferase assay. No
      formation of 5-hydroxyacetovanillone could be detected in vitro from 5
      hydroxyferuloyl-CoA and NAD in the extracts used to measure acetovanillone
      synthase activity, indicating that 5-hydroxyacetovanillone is probably formed by
      direct hydroxylation of acetovanillone rather than by beta-oxidation of 5
      hydroxyferulic acid. Taken together our results strongly support the hypothesis
      that acetosyringone biosynthesis in tobacco proceeds from feruloyl-CoA via
      acetovanillone and 5-hydroxyacetovanillone.

PMID- 24445178
TI  - Research is needed to determine optimal screening methods to lessen the burden of
      type 2 diabetes in youth.

PMID- 24445179
TI  - Adolescent susceptibility to smoking: the importance of an international
      perspective.

PMID- 24445181
TI  - Influenza vaccine: an updated position statement of the Society for Adolescent
      Health and Medicine.

PMID- 24445180
TI  - Behavioral and psychosocial effects of two middle school sexual health education
      programs at tenth-grade follow-up.
AB  - PURPOSE: An earlier randomized controlled trial found that two middle school
      sexual education programs-a risk avoidance (RA) program and a risk reduction (RR)
      program-delayed initiation of sexual intercourse (oral, vaginal, or anal sex) and
      reduced other sexual risk behaviors in ninth grade. We examined whether these
      effects extended into 10th grade. METHODS: Fifteen middle schools were randomly
      assigned to RA, RR, or control conditions. Follow-up surveys were conducted with
      participating students in 10th grade (n = 1,187; 29.2% attrition). RESULTS:
      Participants were 60% female, 50% Hispanic, and 39% black; seventh grade mean age
      was 12.6 years. In 10th grade, compared with the control condition, both programs
      significantly delayed anal sex initiation in the total sample (RA: adjusted odds
      ratio [AOR], .64, 95% confidence interval [CI], .42-.99; RR: AOR, .65, 95% CI,
      .50-.84) and among Hispanics (RA: AOR, .53, 95% CI, .31-.91; RR: AOR, .82, 95%
      CI, .74-.93). Risk avoidance students were less likely to report unprotected
      vaginal sex, either by using a condom or by abstaining from sex (AOR: .61, 95%
      CI, .45-.85); RR students were less likely to report recent unprotected anal sex
      (AOR: .34, 95% CI, .20-.56). Both programs sustained positive impact on some
      psychosocial outcomes. CONCLUSIONS: Although both programs delayed anal sex
      initiation into 10th grade, effects on the delayed initiation of oral and vaginal
      sex were not sustained. Additional high school sexual education may help to
      further delay sexual initiation and reduce other sexual risk behaviors in later
      high school years.

PMID- 24445182
TI  - Should local anesthetic bladder cocktails include sodium bicarbonate? No.

PMID- 24445183
TI  - Should local anesthetic bladder cocktails include sodium bicarbonate? Yes.

PMID- 24445184
TI  - Determinants of nocturia: pathophysiology and assessment.

PMID- 24445185
TI  - Impact of statins on genitourinary cancer outcomes: the promise and the
      challenge.

PMID- 24445186
TI  - Multiple myeloma and second malignancies.

PMID- 24445187
TI  - Ibrutinib and indolent B-cell lymphomas.
AB  - Most patients with indolent B-cell lymphomas fail to achieve complete remission
      with current treatment approaches and invariably relapse. During the past decade,
      innovative immunochemotherapy strategies have substantially improved disease
      control rates but not survival, thus providing the rationale for development of
      novel agents targeting dysregulated pathways that are operable in these
      hematological malignancies. Ibrutinib, a novel first-in-human Bruton's tyrosine
      kinase (BTK) inhibitor, has progressed into phase III trials after early-phase
      clinical studies demonstrated effective target inhibition, increased tumor
      response rates, and significant improvement in survival, particularly in patients
      with indolent B-cell lymphomas. Recently, the compound was designated a
      "breakthrough therapy" by the United States Food and Drug Administration for the
      treatment of patients with relapsed or refractory mantle cell lymphoma and
      Waldenstrom macroglobulinemia. This review summarizes recent achievements of
      ibrutinib, with a focus on its emerging role in the treatment of patients with
      indolent B-cell lymphoid malignancies.

PMID- 24445188
TI  - BRAF V600E mutation and clonal evolution in a patient with relapsed refractory
      myeloma with plasmablastic differentiation.

PMID- 24445190
TI  - Analysis of traditional knowledge for wild edible mushrooms consumed by residents
      living in Jirisan National Park (Korea).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study aims to record and analyze the
      traditional knowledge of wild edible mushrooms utilized by residents living in
      Jirisan National Park (Korea). MATERIALS AND METHODS: Data was collected through
      participant observations and in-depth interviews with semi-structured
      questionnaires. Quantitative comparative analyses were accomplished through
      informant consensus factor (ICF), fidelity level (FL), and inter-network analysis
      (INA). RESULTS: The amounts of traditional knowledge recorded from the
      communities were 158 practices classified within 22 families, 33 genera, and 38
      species. The representative families were Tricholomataceae (23.20%) followed by
      Pleurotaceae (13.10%), Polyporaceae (8.21%), and Hymenochaetaceae (6.33%). The
      results revealed 24 modes of preparation for the mushrooms, with the most common
      methods being for preparing them as, seasoned cooked mushrooms (40.75%), soups
      (13.84%), teas (12.18%), simmered (9.19%), and roasted (6.20%). The informant
      consensus factor (ICF) values in the ailment categories were birth-related
      disorders (1.00), genitourinary system disorders (1.00), other conditions (0.91),
      circulatory system disorders (0.76), and diabetes (0.33). In terms of fidelity
      levels, five mushroom species showed 100% of fidelities. Regarding the inter
      network analysis (INA) of mushrooms and ailments, the positions of medicinal
      mushrooms is distributed into three main groups. Also, regarding the network of
      mushrooms and foods, the location of edible mushrooms is distributed into two
      main food groups. CONCLUSION: The utilization of the inter-network analysis has
      been used typically within the social sciences for the analysis of social trends
      and phenomena through the interrelationship of specific social components, from
      this study it is being applied for the interpretation of traditional knowledge
      utilizing mushrooms in the local communities. Through this study, we are
      confident that the useful application of the inter-network analysis has been
      successfully proven.

PMID- 24445192
TI  - Direct hydro-liquefaction of sawdust in petroleum ether and comprehensive bio-oil
      products analysis.
AB  - The effect of temperature, time, hydrogen pressure and amount of catalyst on
      production distribution and the bio-oil yield obtained from the direct
      liquefaction of sawdust in the petroleum ether (60-90 degrees C) are
      investigated. The highest sawdust conversion obtained was 72.32% with a bio-oil
      yield of 47.69% were obtained at 370 degrees C, 40min and 5wt.% catalyst content
      with the initial H2 pressure of 3.0MPa. Fourier transform ion cyclotron resonance
      mass spectrometry (FTICR-MS) approach was utilized to analyze the non-volatile
      fraction. In this study, the composition of bio-oil could be analyzed in an
      unprecedented detail through a combination of GC-MS and FT-ICR MS techniques. 

PMID- 24445191
TI  - Interaction among multiple microorganisms and effects of nitrogen and carbon
      supplementations on lignin degradation.
AB  - The mutual interactions among the consortium constructed by four indigenous
      bacteria and five inter-kingdom fusants and the effects of nitrogen and carbon
      supplementations on lignin degradation and laccase activity were investigated.
      Analyzed by Plackett-Burman and central composite design, the microbial
      consortium were optimized, Bacillus sp. (B) and PE-9 and Pseudomonas putida (Pp)
      and PE-9 had significant interactions on lignin degradation based on a 5% level
      of significance. The nitrogen and carbon supplementations played an important
      role in lignin degradation and laccase production. The ultimate lignin
      degradation efficiency of 96.0% and laccase activity of 268U/L were obtained with
      0.5g/L of ammonium chloride and 2g/L of sucrose. Results suggested that a stable
      and effective microbial consortium in alkalescent conditions was successfully
      achieved through the introduction of fusants, which was significant for its
      industrial application. 

PMID- 24445193
TI  - Heterotrophic growth and lipid accumulation of Chlorella protothecoides in whey
      permeate, a dairy by-product stream, for biofuel production.
AB  - This study proposes a novel alternative for the utilization of whey permeate, a
      by-product stream from the dairy industry, as the feedstock for the biomass and
      lipid production of the microalgae Chlorella protothecoides. Glucose and
      galactose from the pre-hydrolyzed whey permeate were used as main carbon sources
      in a base mineral media for establishing batch and fed batch cultures. Batch
      cultures reached a biomass production of 9.1+/-0.2g/L with a total lipid
      accumulation of 42.0+/-6.6% (dry weight basis), while in the fed batch cultures
      17.2+/-1.3g/L of biomass with 20.5+/-0.3% lipid accumulation (dry weight basis)
      were obtained. A third strategy for the direct utilization of whey permeate was
      investigated by simultaneous saccharification and fermentation (SSF), wherein,
      7.3+/-1.3g/L of biomass with 49.9+/-3.3% lipid accumulation (dry weight basis)
      was obtained in batch mode using immobilized enzyme. 

PMID- 24445189
TI  - Stromal regulation of embryonic and postnatal mammary epithelial development and
      differentiation.
AB  - The stroma, which is composed of supporting cells and connective tissue,
      comprises a large component of the local microenvironment of many epithelial cell
      types, and influences several fundamental aspects of cell behaviour through both
      tissue interactions and niche regulation. The significance of the stroma in
      development and disease has been increasingly recognised. Whereas normal stroma
      is essential for various developmental processes during vertebrate organogenesis,
      it can be deregulated and become abnormal, which in turn can initiate or promote
      a disease process, including cancer. The mouse mammary gland has emerged in
      recent years as an excellent model system for understanding stromal function in
      both developmental and cancer biology. Here, we take a systematic approach and
      focus on the dynamic interactions that the stroma engages with the epithelium
      during mammary specification, cell differentiation, and branching morphogenesis
      of both the embryonic and postnatal development of the mammary gland. Similar
      stromal-epithelial interactions underlie the aetiology of breast cancer, making
      targeting the cancer stroma an increasingly important and promising therapeutic
      strategy to pursue for breast cancer treatment. 

PMID- 24445194
TI  - Integrated simultaneous desulfurization and denitrification (ISDD) process at
      various COD/sulfate ratios.
AB  - The integrated simultaneous desulfurization and denitrification (ISDD) is a novel
      treatment process to handle sulfate and nitrate-laden wastewaters of high
      loadings. This study experimentally explored the effect of COD/SO4(2-) ratio on
      the performance of ISDD process, particularly considering the complex
      interactions between sulfate-reducing bacteria (SRB), heterotrophic denitrifiers
      (hNRB) and autotrophic denitrifiers (aNRB). There existed an optimal COD/SO4(2-)
      ratio (=1.5:1 in the present study) to reach 100% SO4(2-) and NO3(-) removals and
      42.6% S(0) recovery. At COD/SO4(2-)=1.5:1, the functional strains could form
      granules with high retention in the ISDD reactor. The microbial community
      analysis identified the SRB, hNRB and aNRB in the studied system, whose shifts
      correlated well with the noted ISDD performance change at different COD/SO4(2-)
      ratio. Interactions between different groups of bacteria and the possible
      strategy to enhance the ISDD performance were discussed. 

PMID- 24445195
TI  - Cannabinoid type-1 receptor ligands, alone or in combination with cocaine, affect
      vigilance-related behaviors of marmoset monkeys.
AB  - Endocannabinoids (eCB) have been functionally linked to cocaine's rewarding
      effects. However, results differ at the behavioral level, with few reports in
      nonhuman primates (NHPs). Here we analyzed whether repeatedly administered
      cannabinoid type-1 receptor (CB1r) agonist WIN 55-212,2 (WIN) or antagonist AM
      251 (AM) induce effects per se and if concurrent pre-treatments affect cocaine
      induced changes in marmoset behavior. Six groups were tested: WIN-saline; WIN
      cocaine; AM-saline; AM-cocaine; vehicle-cocaine; and vehicle-saline. Subjects
      were pre-treated with either WIN (1mg/kg), AM (2mg/kg) or vehicle and then
      injected with cocaine (5mg/kg) or saline. Six exposures were held at 48 h
      intervals. Behaviors were scored during 15-min in an open-field on days 1 and 6,
      as well as a withdrawal (WD) trial. Marmosets became hypervigilant during cocaine
      exposures, which did not condition to the injection context. CB1r activation
      induced an equivalent response, whereas AM had no effect on its own. However,
      when given as a pre-treatment to cocaine, CB1r blockade enhanced the former's
      hypervigilance effect and potentially conditioned this response to the exposure
      context. Enhancement may have resulted from AM's inhibition of eCB-potentiated
      cocaine-induced anxiogenesis and/or its action independent of the eCB system, or
      even CB1r-mediated changes in synaptic plasticity involved in cocaine reward
      learning. All effects were independent of motor function. Thus, changes in CB1r
      function - alone and in combination with cocaine - affected stereotyped vigilance
      related behaviors in this NHP, further implicating the eCB system in the
      neurobiological mechanisms of cocaine addiction.

PMID- 24445196
TI  - Assessment of the safety and immunogenicity of Rhodococcus equi-secreted proteins
      combined with either a liquid nanoparticle (IMS 3012) or a polymeric (PET GEL A)
      water-based adjuvant in adult horses and foals--identification of promising new
      candidate antigens.
AB  - Rhodococcus equi is the most common infectious cause of mortality in foals
      between 1 and 6 months of age. Because of an increase in the number of antibiotic
      resistant strains, the optimization of a prophylactic strategy is a key factor in
      the comprehensive management of R. equi pneumonia. The objectives of this study
      were to assess the safety and immunogenicity of R. equi-secreted proteins (ReSP)
      co-administered with either the nanoparticular adjuvant MontanideTM IMS 3012 VG,
      or a new polymeric adjuvant MontanideTM PET GEL A, and to further investigate the
      most immunogenic proteins for subsequent immunization/challenge experiments in
      the development of a vaccine against rhodoccocal pneumonia. The approach involved
      two phases. The first phase aimed to investigate the safety of vaccination in six
      adult horses. The second phase aimed to determine the safety and immunogenicity
      of vaccination in twelve 3-week-old foals. We set out to develop a method based
      on ultrasound measurements for safety assessment in adult horses in order to
      evaluate any in situ changes at the injection site, in the skin or the underlying
      muscle, with quantitative and qualitative data revealing that administration of
      ReSP combined with the Pet Gel A adjuvant led to an increase in local
      inflammation, associated with 4- to 7-fold higher levels of anti-R. equi IgGa,
      IgGb and IgGT, compared to administration of ReSP associated with IMS 3012
      adjuvant, but without any impact on animal demeanor. Investigations were then
      performed in foals with serological and clinical follow-up until 6 months of age.
      Interestingly, we observed in foals a much lower incidence of adverse local
      tissue reactions at the injection site than in adult horses, with transient and
      moderate swelling for the group that received ReSP combined with Pet Gel A.
      Immunized foals with Pet Gel A adjuvant exhibited a similar response in both IgGa
      and IgGT levels, but a lower response in IgGb levels, compared to adult horses,
      with a subisotype profile that may however reflect a bias favorable to R. equi
      resistance. From the crude extract of secreted proteins, dot-blot screening
      enabled identification of cholesterol oxidase, mycolyl transferase 3, and PSP
      (probable secreted protein) as the most immunogenic candidates. Taken together,
      these results are encouraging in developing a vaccine for foals.

PMID- 24445197
TI  - Cluster headache: Is age of onset important for clinical presentation?
AB  - BACKGROUND: The age of onset of cluster headache (CH) attacks most commonly is
      between 20 and 40 years old, although CH has been reported in all age groups.
      There is increasing evidence of CH with early or late onset and a different
      course of the disorder. The aim of the study was to analyze the influence of the
      age of onset on clinical features, disorder course, and therapy effectiveness in
      CH patients. METHODS: A retrospective and cross-sectional analysis was performed
      on 182 CH patients divided into three groups according to the age of onset. The
      first group consisted of patients with the first CH attack before 20 years of
      age, the second group was patients with age of onset between 20 and 40 years of
      age, and the third group was patients with age of onset after 40 years of age.
      Demographic data, features of CH periods and attacks, and the response to
      standardized treatment were compared among the groups. RESULTS: Patients with CH
      onset after 40 years of age reported a lower number of autonomic features and
      less frequently had conjunctival injection and nasal congestion/rhinorrhea
      phenomena during their attacks. Diagnostic delay was the longest in the patients
      with CH onset before 20 years of age. CONCLUSION: The influence of the age of
      onset of CH is intriguing for further studies and could possibly extend the
      knowledge about CH pathophysiology. From a clinical point of view, the
      differences in CH presentation are insufficient to preclude a correct diagnosis
      and treatment because the same criteria could be applied regardless of patient
      age.

PMID- 24445198
TI  - Effects of malnutrition on children's immunity to bacterial antigens in Northern
      Senegal.
AB  - To evaluate immunity to vaccine-preventable diseases according to nutritional
      status, a longitudinal study was conducted in Senegalese children ages 1-9 years
      old. A linear regression analysis predicted that weight for age was positively
      associated with immunoglobulin G (IgG) response to tetanus toxoid in children
      born during the rainy season or at the beginning of the dry season. A
      relationship between village, time of visits, and levels of antibodies to tetanus
      showed that environmental factors played a role in modulating humoral immunity to
      tetanus vaccine over time. Moreover, a whole-blood stimulation assay highlighted
      that the production of interferon-gamma (IFN-gamma) in response to tetanus toxoid
      was compromised in stunted children. However, the absence of cytokine modulation
      in response to Mycobacterium tuberculosis-purified protein derivatives and
      phytohemagglutinin suggests that the overall ability to produce IFN-gamma was
      preserved in stunted children. Therefore, these results show that nutritional
      status can specifically alter the efficacy of long-lasting immunity to tetanus.

PMID- 24445199
TI  - Logistics of Guinea worm disease eradication in South Sudan.
AB  - From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new
      Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial
      programmatic challenges. Program logistics have played a key role in program
      achievements to date. The program uses disease surveillance and program
      performance data and integrated technical-logistical staffing to maintain
      flexible and effective logistical support for active community-based surveillance
      and intervention delivery in thousands of remote communities. Lessons learned
      from logistical design and management can resonate across similar complex
      surveillance and public health intervention delivery programs, such as mass drug
      administration for the control of neglected tropical diseases and other disease
      eradication programs. Logistical challenges in various public health scenarios
      and the pivotal contribution of logistics to Guinea worm case reductions in South
      Sudan underscore the need for additional inquiry into the role of logistics in
      public health programming in low-income countries.

PMID- 24445200
TI  - Unusual genotypic distribution of Orientia tsutsugamushi strains causing human
      infections on Jeju Island.
AB  - We investigated the clinical characteristics and serologic types of tsutsugamushi
      disease on the largest island of South Korea. There were 141 patients with
      tsutsugamushi disease at Jeju National University Hospital and Seogwipo Medical
      Center between November of 2003 and December of 2012. Median age of patients was
      61 years, and 59% were women. The major clinical manifestations were fever
      (80.5%) and skin rash (55.7%), with eschars evident in 75.8% of the patients.
      Genotype analysis of Orientia tsutsugamushi was conducted in 33 specimens. The
      genotype was identified as Boryong type in 17 of 33 patients and Taguchi type in
      15 of 33 patients. In our study, although the Taguchi genotype is rarely reported
      in the endemic area, it was common on Jeju Island. This genotype may be
      associated with mild and moderate forms of tsutsugamushi disease.

PMID- 24445201
TI  - Anticomplementary activity of horse IgG and F(ab')2 antivenoms.
AB  - Envenomation by poisonous animals is a neglected condition according to the World
      Health Organization (WHO). Antivenoms are included in the WHO Essential Medicines
      List. It has been assumed that immunoglobulin G (IgG) antivenoms could activate
      the complement system through Fc and induce early adverse reactions (EARs).
      However, data in the literature indicate that F(ab')2 fragments can also activate
      the complement system. Herein, we show that several batches of IgG and F(ab')2
      antivenoms from the Butantan, Vital Brazil, and Clodomiro Picado Institutes
      activated the complement classical pathway and induced the production of C3a;
      however, only those antivenoms from Clodomiro Picado generated C5a. Different
      protein profiles (IgG heavy chain, protein contaminants, and aggregates) were
      observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and Western blot analyses. Our results show that various antivenoms from
      different producers are able to activate the classical pathway of the complement
      system and generate anaphylatoxins, and these findings suggest that factors, such
      as composition, contaminant proteins, and aggregates, may influence the
      anticomplementary activity of antivenoms in vitro. Therefore, there is a need to
      further improve antivenom production methods to reduce their anticomplementary
      activity and potential to cause EARs.

PMID- 24445202
TI  - High prevalence of Rickettsia typhi and Bartonella species in rats and fleas,
      Kisangani, Democratic Republic of the Congo.
AB  - The prevalence and identity of Rickettsia and Bartonella in urban rat and flea
      populations were evaluated in Kisangani, Democratic Republic of the Congo (DRC)
      by molecular tools. An overall prevalence of 17% Bartonella species and 13%
      Rickettsia typhi, the agent of murine typhus, was found in the cosmopolitan rat
      species, Rattus rattus and Rattus norvegicus that were infested by a majority of
      Xenopsylla cheopis fleas. Bartonella queenslandensis, Bartonella elizabethae, and
      three Bartonella genotypes were identified by sequencing in rat specimens, mostly
      in R. rattus. Rickettsia typhi was detected in 72% of X. cheopis pools, the main
      vector and reservoir of this zoonotic pathogen. Co-infections were observed in
      rodents, suggesting a common mammalian host shared by R. typhi and Bartonella
      spp. Thus, both infections are endemic in DRC and the medical staffs need to be
      aware knowing the high prevalence of impoverished populations or
      immunocompromised inhabitants in this area.

PMID- 24445203
TI  - Pre-travel preparation of US travelers going abroad to provide humanitarian
      service, Global TravEpiNet 2009-2011.
AB  - We analyzed characteristics of humanitarian service workers (HSWs) seen pre
      travel at Global TravEpiNet (GTEN) practices during 2009-2011. Of 23,264
      travelers, 3,663 (16%) travelers were classified as HSWs. Among HSWs, 1,269 (35%)
      travelers were medical workers, 1,298 (35%) travelers were non-medical service
      workers, and 990 (27%) travelers were missionaries. Median age was 29 years, and
      63% of travelers were female. Almost one-half (49%) traveled to 1 of 10
      countries; the most frequent destinations were Haiti (14%), Honduras (8%), and
      Kenya (6%). Over 90% of travelers were vaccinated for or considered immune to
      hepatitis A, typhoid, and yellow fever. However, for hepatitis B, 292 (29%) of
      990 missionaries, 228 (18%) of 1,298 non-medical service workers, and 76 (6%) of
      1,269 medical workers were not vaccinated or considered immune. Of HSWs traveling
      to Haiti during 2010, 5% of travelers did not receive malaria chemoprophylaxis.
      Coordinated efforts from HSWs, HSW agencies, and clinicians could reduce vaccine
      coverage gaps and improve use of malaria chemoprophylaxis.

PMID- 24445204
TI  - Molecular detection of Rickettsia felis and Bartonella henselae in dog and cat
      fleas in Central Oromia, Ethiopia.
AB  - Fleas are important vectors of several Rickettsia and Bartonella spp. that cause
      emerging zoonotic diseases worldwide. In this study, 303 fleas collected from
      domestic dogs and cats in Ethiopia and identified morphologically as
      Ctenocephalides felis felis, C. canis, Pulex irritans, and Echidnophaga
      gallinacea were tested for Rickettsia and Bartonella DNA by using molecular
      methods. Rickettsia felis was detected in 21% of fleas, primarily C. felis, with
      a similar prevalence in fleas from dogs and cats. A larger proportion of flea
      infested dogs (69%) than cats (37%) harbored at least one C. felis infected with
      R. felis. Rickettsia typhi was not detected. Bartonella henselae DNA was detected
      in 6% (2 of 34) of C. felis collected from cats. Our study highlights the
      likelihood of human exposure to R. felis, an emerging agent of spotted fever, and
      B. henselae, the agent of cat-scratch disease, in urban areas in Ethiopia.

PMID- 24445205
TI  - Importance of cholera and other etiologies of acute diarrhea in post-earthquake
      Port-au-Prince, Haiti.
AB  - We estimated the proportion of diarrhea attributable to cholera and other
      pathogens during the rainy and dry seasons in patients seen in two urban health
      settings: a cholera treatment center (CTC) and oral rehydration points (ORPs).
      During April 1, 2011-November 30, 2012, stool samples were collected from 1,206
      of 10,845 patients who came to the GHESKIO CTC or to the community ORPs with
      acute diarrhea, cultured for Vibrio cholerae, and tested by multiplex polymerase
      reaction. Vibrio cholerae was isolated from 409 (41.8%, 95% confidence interval
      [CI] = 38.7-44.9%) of the 979 specimens from the CTC and in 45 (19.8%, 95% CI =
      14.8-25.6%) of the 227 specimens from the ORPs. Frequencies varied from 21.4%
      (95% CI = 16.6-26.7%) during the dry season to 46.8% (95% CI = 42.9-50.7%) in the
      rainy season. Shigella, enterotoxigenic Escherichia coli, rotavirus, and
      Cryptosporidium were frequent causes of diarrhea in children less than five years
      of age.

PMID- 24445206
TI  - Improving global health education: development of a Global Health Competency
      Model.
AB  - Although global health is a recommended content area for the future of education
      in public health, no standardized global health competency model existed for
      master-level public health students. Without such a competency model, academic
      institutions are challenged to ensure that students are able to demonstrate the
      knowledge, skills, and attitudes (KSAs) needed for successful performance in
      today's global health workforce. The Association of Schools of Public Health
      (ASPH) sought to address this need by facilitating the development of a global
      health competency model through a multistage modified-Delphi process.
      Practitioners and academic global health experts provided leadership and guidance
      throughout the competency development process. The resulting product, the Global
      Health Competency Model 1.1, includes seven domains and 36 competencies. The
      Global Health Competency Model 1.1 provides a platform for engaging educators,
      students, and global health employers in discussion of the KSAs needed to improve
      human health on a global scale.

PMID- 24445207
TI  - Alteration of the phenotypic and pathogenic patterns of Burkholderia pseudomallei
      that persist in a soil environment.
AB  - Melioidosis is caused by the soil-borne pathogen Burkholderia pseudomallei. To
      investigate whether the distinct phenotypic and virulent characteristics result
      from environmental adaptations in the soil or from the host body, two pairs of
      isogenic strains were generated by passages in soil or mice. After cultivation in
      soil, the levels of 3-hydroxytetradecanoic acid, biofilm formation, flagellar
      expression, and ultrastructure were altered in the bacteria. Uniformly fatal
      melioidosis developed as a result of infection with mouse-derived strains;
      however, the survival rates of mice infected with soil-derived strains prolonged.
      After primary infection or reinfection with soil-derived strains, the mice
      developed a low degree of bacterial hepatitis and bacterial colonization in the
      liver and bone marrow compared with mice that were infected with isogenic or
      heterogenic mouse-derived strains. We suggest that specific phenotypic and
      pathogenic patterns can be induced through infection with B. pseudomallei that
      has been cultured in different (soil versus mouse) environments.

PMID- 24445208
TI  - Effect of dengue-2 virus infection on protein expression in the salivary glands
      of Aedes aegypti mosquitoes.
AB  - Dengue virus (DENV) is the most important mosquito-transmitted flavivirus that is
      transmitted throughout the tropical and subtropical regions of the world. The
      primary mosquito vector of DENV in urban locations is Aedes aegypti. Key to
      understanding the transmission of DENV is the relationship between pathogen and
      vector. Accordingly, we report our preliminary characterization of the
      differentially expressed proteins from Ae. aegypti mosquitoes after DENV
      infection. We investigated the virus-vector interaction through changes in the
      proteome of the salivary glands of mosquitoes with disseminated DENV serotype 2
      (DENV-2) infections using two-dimensional gel electrophoresis and identification
      by mass spectrometry. Our findings indicate that DENV-2 infection in the Ae.
      aegypti salivary gland alters the expression of structural, secreted, and
      metabolic proteins. These changes in the salivary gland proteome highlight the
      virally influenced environment caused by a DENV-2 infection and warrant
      additional investigation to determine if these differences extend to the
      expectorated saliva.

PMID- 24445209
TI  - Household characteristics associated with rodent presence and Leptospira
      infection in rural and urban communities from Southern Chile.
AB  - Rodents are well-recognized reservoirs of Leptospira, contributing to its
      maintenance in endemic areas and playing a role in the public health risk
      associated with the infection. This study sought to provide some insights into
      rodent populations from Chile and their Leptospira carriage. In total, 393
      rodents were trapped in 177 households. Higher rodent counts were associated with
      year 2 of the study, rainfall, and number of rodent signs. There was an inverse
      correlation with the number of cats. The number of rodents was higher in villages
      compared with slums (rate ratio = 3.23) but modified by average household age.
      Eighty rodents (20.4%) tested positive for Leptospira: 19.7% on the farms, 25.9%
      in villages, and 12.3% in the slums. Prevalence was 22.5% in Mus musculus, 20.7%
      in Rattus rattus, 21.1% in wild rodents, and 10.3% in R. norvegicus. Seasonal and
      temporal effects were the major determinants of Leptospira infection in rodent
      populations.

PMID- 24445210
TI  - Physicochemical factors affecting the growth of Burkholderia pseudomallei in soil
      microcosm.
AB  - Burkholderia pseudomallei causes melioidosis, the third most common cause of
      death from infectious diseases in northeast Thailand. Four physicochemical
      factors were set so that their values covered the range of the northeast, which
      is an endemic area. The soil pH was set at pH 4-10, soil salinity was 0.0-5.0%
      NaCl, total iron was 50-150 mg/kg soil, and carbon to nitrogen ratio (C/N) was
      10:1 to 40:1. The experiments were carried out at 37 degrees C, and soil moisture
      was maintained for 7 days. The number of viable bacterial cells was counted
      daily. Soil pH, salinity, Fe, and C/N ratio affected the bacterial growth. The
      bacterial colony was significantly (P < 0.05) reduced at soil pH > 8, soil
      salinity > 1% NaCl, and C/N ratio > 40:1. However, the growth of B. pseudomallei
      was enhanced by increasing the concentrations of iron significantly (P < 0.05).
      We propose using these findings to control B. pseudomallei in situ.

PMID- 24445215
TI  - Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty
      liver disease.
AB  - BACKGROUND & AIMS: A third of the population are estimated to have NAFLD of
      varying severity. Serum immunoglobulins are frequently elevated in patients with
      chronic liver disease, but little is known about serum immunoglobulin levels in
      patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin
      levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD
      and determine if immunoglobulin levels are associated with clinical or
      histological features. METHODS: Patients seen in a tertiary fatty liver clinic
      between 1999 and 2009 were included. Liver biopsies were assessed using the
      Kleiner score. Immunoglobulin levels and other blood tests were taken at time of
      biopsy. RESULTS: 285 patients (110 simple steatosis and 175 NASH) had serum
      immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had
      elevated (>1* upper limit of normal) serum IgA levels, 28 (10%) patients had
      elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more
      frequently in patients with NASH compared with subjects with simple steatosis
      (55% vs. 31%, p<0.001). Overall, 55 (19%) patients had advanced liver fibrosis
      (Kleiner stage 3-4). There was a significant positive association between serum
      IgA levels and the stage of fibrosis (p<0.001). Serum IgA, age, platelets,
      AST/ALT ratio and BMI were all independently with advanced fibrosis following
      multivariate analysis. A model constructed from these independent predictors
      accurately predicted advanced fibrosis (AUROC 0.87). CONCLUSIONS: The serum IgA
      level was frequently elevated in patients with NAFLD and was an independent
      predictor of advanced fibrosis.

PMID- 24445212
TI  - Bail-out transcatheter aortic valve implantation to reduce severe acute aortic
      regurgitation in a failing homograft secondary to HeartMate II ventricular
      assistance device.
AB  - Left ventricular assistance with surgically implanted pump devices like the
      HeartMate may be crucial in selected patient with end-stage heart failure.
      However, mainly due to its high aortic output, the pump itself may induce severe
      aortic regurgitation that could result in paradoxycal worsening of the
      anterograde perfusion after the initiation of the support. Surgical or
      percutaneous occlusion of the aortic valve has proved useful in these kinds of
      patients. Here we present a successful case of bail-out CoreValve implantation
      after HeartMate II positioning complicated by acute severe aortic regurgitation
      in a patient with a failing homograft and end-stage ventricular dysfunction,
      ineligible for heart transplanation. 

PMID- 24445211
TI  - Diagnostic accuracy of Kato-Katz, FLOTAC, Baermann, and PCR methods for the
      detection of light-intensity hookworm and Strongyloides stercoralis infections in
      Tanzania.
AB  - Sensitive diagnostic tools are crucial for an accurate assessment of helminth
      infections in low-endemicity areas. We examined stool samples from Tanzanian
      individuals and compared the diagnostic accuracy of a real-time polymerase chain
      reaction (PCR) with the FLOTAC technique and the Kato-Katz method for hookworm
      and the Baermann method for Strongyloides stercoralis detection. Only FLOTAC had
      a higher sensitivity than the Kato-Katz method for hookworm diagnosis; the
      sensitivities of PCR and the Kato-Katz method were equal. PCR had a very low
      sensitivity for S. stercoralis detection. The cycle threshold values of the PCR
      were negatively correlated with the logarithm of hookworm egg and S. stercoralis
      larvae counts. The median larvae count was significantly lower in PCR false
      negatives than true positives. All methods failed to detect very low-intensity
      infections. New diagnostic approaches are needed for monitoring of progressing
      helminth control programs, confirmation of elimination, or surveillance of
      disease recrudescence.

PMID- 24445217
TI  - Renal impairment and anemia during triple therapy.

PMID- 24445216
TI  - Mindin/Spondin 2 inhibits hepatic steatosis, insulin resistance, and obesity via
      interaction with peroxisome proliferator-activated receptor alpha in mice.
AB  - BACKGROUND & AIMS: Obesity and its related pathologies, such as hepatic
      steatosis, are associated with chronic inflammation and insulin resistance (IR),
      which contribute to cardiovascular disease. Our previous studies indicated that
      Spondin 2 has a protective role in the context of cardiovascular and
      cerebrovascular diseases. Whether Spondin 2 is also associated with the
      development of hepatic steatosis and IR remains unclear. METHODS: Wild-type mice,
      Spondin 2-knockout (KO) mice, hepatic-specific Spondin 2 transgenic (Spondin 2
      TG) mice, high fat diet (HFD)-induced obese mice injected with an adenovirus
      expressing Spondin 2-specific shRNA or a Spondin 2 mutant and genetically obese
      (ob/ob) mice injected with an adenovirus expressing Spondin 2 were fed normal
      chow (NC) or HFD for indicated time to induce obesity, hepatic steatosis,
      inflammation, and IR. Biomedical, histological, and metabolic analyses were
      conducted to identify pathologic alterations in these mice. The molecular
      mechanisms of Spondin 2 functions were explored in mice and in hepatocytes or
      cell lines. RESULTS: Consistent with Spondin 2 repression in the livers of HFD
      induced and ob/ob mice, the Spondin 2-KO or hepatic-specific Spondin 2 knockdown
      mice exhibited more severe obesity, hepatic steatosis, inflammation, and IR upon
      HFD. Conversely, these pathological conditions were significantly improved in the
      Spondin 2-TG mice or Spondin 2-overexpressing ob/ob mice. Spondin 2 interacts
      with PPARalpha to regulate PPARalpha-target genes, thereby improving the
      pathological phenotypes. In contrast, the hepatic overexpression of mutant
      Spondin 2 without the PPARalpha-interacting domain failed to improve the
      aggravated phenotypes observed in the Spondin 2-KO mice. CONCLUSION: Spondin 2
      regulates hepatic lipid metabolism and alleviates hepatic steatosis, obesity,
      inflammation, and IR in mice via its interaction with PPARalpha.

PMID- 24445218
TI  - Reply to: "Renal impairment and anemia during triple therapy".

PMID- 24445220
TI  - Reply to: 'Evidence recommending antiviral therapy in hepatitis C'.

PMID- 24445219
TI  - Development of new fatty liver, or resolution of existing fatty liver, over five
      years of follow-up, and risk of incident hypertension.
AB  - BACKGROUND & AIMS: Approximately 50% of hypertensive patients have non-alcoholic
      fatty liver disease (NAFLD), but whether change in fatty liver status over time
      modifies risk of developing hypertension is uncertain. Our aim was to determine
      whether a change in fatty liver status (either development of new fatty liver, or
      resolution of existing fatty liver) over five years modified risk of incident
      hypertension at five year follow-up. METHODS: 11,448 patients without
      hypertension were examined at baseline and at five year follow-up, using a
      retrospective cohort study design. Fatty liver status (absent or present) was
      assessed at baseline and follow-up using standard ultrasound criteria. Adjusted
      odds ratios (aOR) and 95% confidence intervals (CIs) for incident hypertension at
      follow-up were estimated controlling for potential confounders, compared to the
      reference group (patients who did not have fatty liver at either baseline or
      follow-up). RESULTS: 911 patients developed incident hypertension. Incident fatty
      liver developed during follow-up in 1418 patients and fatty liver at baseline
      resolved during follow-up in 684 patients. Developing incident fatty liver was
      associated with incident hypertension, even after adjustment for multiple
      confounders (aOR=1.60 (95% CI 1.30, 1.96; p<0.001). Further adjustment for change
      in body mass index between baseline and follow-up only slightly attenuated this
      association (aOR=1.36 (95% CI 1.10, 1.67; p=0.004). With resolution of fatty
      liver at follow-up, risk of incident hypertension was not different from the
      reference group (aOR=1.21 (95% CI 0.90, 1.63; p=0.21). CONCLUSIONS: Development
      of incident fatty liver is associated with increased risk of hypertension.

PMID- 24445221
TI  - Evidence recommending antiviral therapy in hepatitis C.

PMID- 24445222
TI  - Regulation of pH attenuates toxicity of a byproduct produced by an ethanologenic
      strain of Sphingomonas sp. A1 during ethanol fermentation from alginate.
AB  - Marine macroalgae is a promising carbon source that contains alginate and
      mannitol as major carbohydrates. A bioengineered ethanologenic strain of the
      bacterium Sphingomonas sp. A1 can produce ethanol from alginate, but not
      mannitol, whereas the yeast Saccharomyces paradoxus NBRC 0259-3 can produce
      ethanol from mannitol, but not alginate. Thus, one practical approach for
      converting both alginate and mannitol into ethanol would involve two-step
      fermentation, in which the ethanologenic bacterium initially converts alginate
      into ethanol, and then the yeast produces ethanol from mannitol. In this study,
      we found that, during fermentation from alginate, the ethanologenic bacterium
      lost viability and secreted toxic byproducts into the medium. These toxic
      byproducts inhibited bacterial growth and killed bacterial cells and also
      inhibited growth of S. paradoxus NBRC 0259-3. We discovered that adjusting the pH
      of the culture supernatant or the culture medium containing the toxic byproducts
      to 6.0 attenuated the toxicity toward both bacteria and yeast, and also extended
      the period of viability of the bacterium. Although continuous adjustment of pH to
      6.0 failed to improve the ethanol productivity of this ethanologenic bacterium,
      this pH adjustment worked very well in the two-step fermentation due to the
      attenuation of toxicity toward S. paradoxus NBRC 0259-3. These findings provide
      information critical for establishment of a practical system for ethanol
      production from brown macroalgae. 

PMID- 24445224
TI  - N-terminal prohormone of brain natriuretic peptide--how far can we extrapolate?

PMID- 24445223
TI  - Traditional nurse triage vs physician telepresence in a pediatric ED.
AB  - OBJECTIVES: The objective of the study is to compare traditional nurse triage
      (TNT) in a pediatric emergency department (PED) with physician telepresence
      (PTP). METHODS: This is a prospective 2 * 2 crossover study with random
      assignment using a sample of walk-in patients seeking care in a PED at a large,
      tertiary care children's hospital, from May 2012 to January 2013. Outcomes of
      triage times, documentation errors, triage scores, and survey responses were
      compared between TNT and PTP. Comparison between PTP to actual treating PED
      physicians regarding the accuracy of ordering blood and urine tests, throat
      cultures, and radiologic imaging was also studied. RESULTS: Paired samples t
      tests showed a statistically significant difference in triage time between TNT
      and PTP (P = .03) but no significant difference in documentation errors (P =
      .10). Triage scores of TNT were 71% accurate, compared with PTP, which were 95%
      accurate. Both parents and children had favorable scores regarding PTP, and most
      indicated that they would prefer PTP again at their next PED visit. Physician
      telepresence diagnostic ordering was comparable with the actual PED physician
      ordering, showing no statistical differences. CONCLUSIONS: Using PTP technology
      to remotely perform triage is a feasible alternative to traditional nurse triage,
      with no clinically significant differences in time, triage scores, errors, and
      patient and parent satisfaction.

PMID- 24445225
TI  - High levels of serum macrophage migration inhibitory factor and interleukin 10
      are associated with a rapidly fatal outcome in patients with severe sepsis.
AB  - OBJECTIVES: The aim of this study was to delineate the association between high
      macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in
      the early phase of sepsis and rapidly fatal outcome. METHODS: One hundred and
      fifty-three adult subjects with the main diagnosis of severe sepsis (including
      septic shock) admitted directly from the emergency department of two tertiary
      medical centers and one regional teaching hospital between January 2009 and
      December 2011, were included prospectively. MIF and IL-10 levels were measured
      and outcomes were analyzed by Cox regression analysis according to the following
      outcomes: rapidly fatal outcome (RFO, death within 48 h), late fatal outcome
      (LFO, death between 48 h and 28 days), and survival at 28 days. RESULTS: Among
      the three outcome groups, IL-10 levels were significantly higher in the RFO group
      (p < 0.001) and no significant differences were seen between the LFO and survivor
      groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml
      in both IL-10 and MIF was independently associated with RFO in patients with
      severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the
      RFO risk by a factor of 1.312 (95% confidence interval 1.094-1.575; p=0.003);
      this was the most significant factor leading to RFO in patients with severe
      sepsis. CONCLUSIONS: Patients with RFO exhibited simultaneously high MIF and IL
      10 levels in the early phase of severe sepsis. Incremental increases in both IL
      10 and MIF levels were associated with RFO in this patient group, and of the two,
      IL-10 was the most significant factor linked to RFO.

PMID- 24445226
TI  - Molecular epidemiology and genetic characterization of hepatitis B virus in the
      Indian subcontinent.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a gradually evolving virus. The aim of
      this study was to characterize the distribution pattern of HBV genotypes and
      subgenotypes and HBsAg subtypes in chronic hepatitis B subjects from the Indian
      subcontinent. We also sought to investigate the genetic diversity of HBV
      genotypes and its influence on the therapeutic response. METHODS: A total of 295
      chronic hepatitis B subjects were studied. HBV genotypes and subgenotypes were
      determined using the generated HBV reverse transcriptase (rt) sequences. HBsAg
      subtypes were predicted using a newly developed automated program in Microsoft
      Visual Basic (VB6). Genetic diversity was characterized by calculating the mean
      genetic distance (d), the number of synonymous substitutions per synonymous site
      (dS), and the number of non-synonymous substitutions per non-synonymous site
      (dN). The virological response was measured by HBV DNA levels. RESULTS: In
      southern India, the predominant HBV subgenotype/subtype was D2/ayw3 (79.1%). In
      eastern India, C1/adr (28.2%) was found to be the predominant
      subgenotype/subtype, followed by A1/adw2 (25.4%). In the north-eastern region,
      C2/adr, D2/ayw3, and D5/ayw3 were predominant and were each identified in 20.8%
      of subjects. In treatment-naive subjects, the d, dS, and dN of genotype D
      sequences were higher compared to genotypes C and A. Additionally, the d, dS, and
      dN of HBV rt sequence were higher in subjects who subsequently showed a
      virological response to nucleos(t)ide analogues as compared to non-responders,
      irrespective of the genotypes tested (p=0.014 to p<0.0001). CONCLUSIONS: We have
      described the distribution of HBV genotypes and subgenotypes and HBsAg subtypes
      in three major regions of the Indian subcontinent. HBV genetic diversity may play
      a pivotal role in the clinical outcome of chronic hepatitis B.

PMID- 24445227
TI  - Relation between the expression of mitotic centromere-associated kinesin and the
      progression of squamous cell carcinoma of the tongue.
AB  - OBJECTIVE: Mitotic centromere-associated kinesin (MCAK) is a microtubule
      depolymerase indispensable for microtubule binding during spindle formation. The
      purpose of this study was to investigate the association of MCAK expression with
      squamous cell carcinoma of the oral tongue (SCCOT). STUDY DESIGN:
      Immunohistochemistry was used in 47 cases of SCCOT. Determination of
      proliferation and migratory capabilities was performed with 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell
      chamber assay, respectively, on cells from the human tongue squamous cell
      carcinoma cell line Tca8113 that were transfected with MCAK small interfering RNA
      (siRNA). RESULTS: MCAK expression level in oral tongue cancer tissue is
      significantly higher (P < .01) than that of corresponding normal tissue. In
      addition, high expression of MCAK is significantly associated with lymph node
      metastasis (P < .05) and tumor staging (P < .01). Moreover, gene silencing of
      MCAK suppresses proliferation and migration of Tca8113 cells (P < .05; P < .01).
      CONCLUSIONS: The expression of MCAK may be associated with the progression of
      SCCOT.

PMID- 24445228
TI  - Sudden cardiac death risk stratification in patients with nonischemic dilated
      cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to provide a meta-analysis to estimate
      the performance of 12 commonly reported risk stratification tests as predictors
      of arrhythmic events in patients with nonischemic dilated cardiomyopathy.
      BACKGROUND: Multiple techniques have been assessed as predictors of death due to
      ventricular tachyarrhythmias/sudden death in patients with nonischemic dilated
      cardiomyopathy. METHODS: Forty-five studies enrolling 6,088 patients evaluating
      the association between arrhythmic events and predictive tests (baroreflex
      sensitivity, heart rate turbulence, heart rate variability, left ventricular end
      diastolic dimension, left ventricular ejection fraction, electrophysiology study,
      nonsustained ventricular tachycardia, left bundle branch block, signal-averaged
      electrocardiogram, fragmented QRS, QRS-T angle, and T-wave alternans) were
      included. Raw event rates were extracted, and meta-analysis was performed using
      mixed effects methodology. We also used the trim-and-fill method to estimate the
      influence of missing studies on the results. RESULTS: Patients were 52.8 +/- 14.5
      years of age, and 77% were male. Left ventricular ejection fraction was 30.6 +/-
      11.4%. Test sensitivities ranged from 28.8% to 91.0%, specificities from 36.2% to
      87.1%, and odds ratios from 1.5 to 6.7. Odds ratio was highest for fragmented QRS
      and TWA (odds ratios: 6.73 and 4.66, 95% confidence intervals: 3.85 to 11.76 and
      2.55 to 8.53, respectively) and lowest for QRS duration (odds ratio: 1.51, 95%
      confidence interval: 1.13 to 2.01). None of the autonomic tests (heart rate
      variability, heart rate turbulence, baroreflex sensitivity) were significant
      predictors of arrhythmic outcomes. Accounting for publication bias reduced the
      odds ratios for the various predictors but did not eliminate the predictive
      association. CONCLUSIONS: Techniques incorporating functional parameters,
      depolarization abnormalities, repolarization abnormalities, and arrhythmic
      markers provide only modest risk stratification for sudden cardiac death in
      patients with nonischemic dilated cardiomyopathy. It is likely that combinations
      of tests will be required to optimize risk stratification in this population.

PMID- 24445229
TI  - Successful treatment of cardiogenic shock with an intraaortic  balloon pump
      following aluminium phosphide  poisoning.
AB  - Aluminium phosphide (AlP) is a highly toxic pesticide that inhibits cytochrome
      oxidase c and causes oxidative stress. Death results from refractory cardiogenic
      shock due to myocardial dysfunction. There is very little information regarding
      extracorporeal life support in severe AlP poisoning. Although several therapies
      are available, none are curative. We report on the use of an intra-aortic balloon
      pump (IABP) in a 24-year-old woman brought to our hospital after an intentional
      ingestion of a tablet of AlP (3 g), which caused refractory AlP-induced
      cardiogenic shock and acute respiratory distress syndrome (ARDS). The patient
      underwent gastric lavage with potassium permanganate, received sodium bicarbonate
      intravenously, and was admitted to the intensive care unit. Echocardiography at
      36 h post ingestion showed a left ventricular ejection fraction (LVEF) of <20 %.
      An IABP was inserted and the patient's vital signs stabilised. After eight days,
      the IABP was removed and on day 20, the patient's LVEF increased to 50 %. IABP
      was successfully used and may improve future prognoses for severely poisoned AlP
      patients with refractory cardiogenic shock. We encourage clinical toxicologists
      to examine this new treatment.

PMID- 24445230
TI  - The Telemedical Rescue Assistance System "TemRas"--development, first results,
      and impact.
AB  - German emergency medical services (EMS) face the challenge of ensuring high
      quality emergency care against a background of continuously increasing numbers of
      emergency missions, resource shortages concomitant with greatly increased arrival
      times, particularly in rural areas. Because German EMS physicians are at maximum
      capacity, an immediate response is not always possible, and thus delays in
      commencing advanced life support measures sometimes occur. In such scenarios,
      paramedics start the initial treatment until the EMS physician arrives. The
      delayed availability of a physician can defer the decision process of the
      paramedics and thus postpone the start of the patient's essential treatment,
      which is particularly dangerous during the care of cardiovascular emergencies.
      Therefore, the project Telemedical Rescue Assistance System (TemRas) has
      developed an innovative concept to improve quality of emergency care. The
      objective is to introduce so-called tele-EMS physicians providing remote medical
      support for the emergency team on site by transmitting audio and video data as
      well as vital signs and 12-lead-ECG from the emergency site to a teleconsultation
      center. In this article, the development process as well as the first results of
      the evaluation phase and the impact for further use of telemedicine in EMS are
      presented.

PMID- 24445231
TI  - Inductive coupling links for lowest misalignment effects in transcutaneous
      implanted devices.
AB  - Use of transcutaneous inductive links is a widely known method for the wireless
      powering of bio-implanted devices such as implanted microsystems. The design of
      the coil for inductive links is generally not optimal. In this study, inductive
      links were used on the basis of the small loop antenna theory to reduce the
      effects of lateral coil misalignments on the biological human tissue model at
      13.56 MHz. The tissue, which measures 60 mm*70 mm*5 mm, separates the reader and
      the implanted coils. The aligned coils and the lateral misalignment coils were
      investigated in different parametric x-distance misalignments. The optimal coil
      layout was developed on the basis of the layout rules presented in previous
      studies. Results show that the gain around the coils, which were separated by wet
      and dry skin, was constant and confirmed the omnidirectional radiation pattern
      even though the lateral misalignment between coils was smaller or greater than
      the implanted coil radius. This misalignment can be <4 mm or >6 mm up to 8 mm.
      Moreover, coil misalignments and skin condition do not affect the efficient
      performance of the coil.

PMID- 24445232
TI  - Differences between external and internal fetal heart rate monitoring during the
      second stage of labor: a prospective observational study.
AB  - OBJECTIVE: To compare fetal heart rate (FHR) signals acquired simultaneously by
      an external ultrasound probe and a scalp electrode during the second stage of
      labor. METHODS: This was a prospective observational study in a labor ward of a
      tertiary care university hospital. The population was women in labor with
      uneventful singleton pregnancies at term. Simultaneous external and internal FHR
      monitoring was performed in 67 consecutively recruited women during the second
      stage of labor. Cases were subsequently excluded if the trace length was under 40
      min, cesarean birth occurred, or the interval between trace-end and birth
      exceeded 5 min, leaving a total of 33 traces for analysis. The last 40-60 min of
      these traces were analyzed by a computer system (Omniview-SisPorto 3.5; Speculum,
      Lisbon, Portugal) to quantify cardiotocographic parameters. Paired sample t-test
      and Bland-Altman limits of agreement (LoA) were used for statistical analysis,
      setting significance at 0.05. The main outcome measures were signal loss, FHR
      baseline, periodic events, and percentage of periodic events coinciding with
      contractions. RESULTS: A higher signal loss was observed with external monitoring
      [10% vs. 4%; P<0.001, LoA=(-6, 18)]. No differences were found in mean FHR
      baseline [129 bpm vs. 130 bpm, P=0.245, LoA=(-15, 12)], but more accelerations
      [12 vs. 8, P<0.001, LoA=(-5, 13)] and less decelerations [8 vs. 10, P<0.001,
      LoA=(-8, 4)] were detected with external monitoring. With this method there were
      also more accelerations (66% vs. 55%, P=0.036) and less decelerations (68% vs.
      81%, P=0.017) coinciding with contractions. CONCLUSIONS: External FHR monitoring
      during the second stage of labor results in higher signal loss, increased number
      of accelerations, and decreased number of decelerations when compared with
      internal monitoring.

PMID- 24445233
TI  - Reference range for amniotic fluid index measurements in a Brazilian population.
AB  - OBJECTIVE: The aim of this study was to determine the reference range for
      amniotic fluid index (AFI) measurements in a large sample of the Brazilian
      population. METHODS: This was a retrospective cross-sectional study on 3837
      normal singleton pregnancies between 18+0 and 38+6 weeks of pregnancy. The AFI
      was measured from the largest vertical pockets of amniotic fluid in the four
      quadrants of the uterine cavity. To assess the correlation between AFI and
      gestational age (GA), polynomial equations were calculated, with adjustments
      using the determination coefficient (R2). RESULTS: The mean maternal age and
      gestational age were 27.01+/-6.57 years and 30.43+/-5.29 weeks, respectively. The
      mean AFI ranged from 12.2+/-2.6 cm at 18 weeks to 11.6+/-6.0 cm at 38 weeks of
      pregnancy. The correlation between AFI and GA was best represented by a linear
      equation: AFI=17.78-0.153*GA (R2=0.027). CONCLUSION: We established the reference
      range for the AFI in a large sample of the Brazilian population. This reference
      range can be used to monitor deviations in the volume of amniotic fluid in
      fetuses at high risk for intrauterine growth disturbances.

PMID- 24445234
TI  - Prenatal diagnosis of sex chromosome aneuploidies and disorders of sex
      development--a retrospective analysis of 11-year data.
AB  - OBJECTIVE: Analysis of prenatally diagnosed sex chromosome aneuploidies and
      disorders of sex development (DSDs). METHODS: This study includes a retrospective
      data analysis of 46 prenatally detected sex chromosome aneuploidies and one case
      of 46,XY DSD diagnosed during an 11-year period (2002-2012) at our department.
      RESULTS: Of the 46 sex chromosome aneuploidies, 29 cases (63.0%) were in the
      group of a selected population of women according to abnormal first-/second
      trimester ultrasound and 17 (37.0%) cases in an unselected population of women
      who underwent fetal karyotyping because of advanced maternal age. The most common
      aneuploidy was Turner syndrome in full and mosaic form (50%). Complete androgen
      insensitivity syndrome was diagnosed in the case of 46,XY DSD. CONCLUSIONS: Sex
      chromosome aneuploidies must be taken into consideration if, in the first or
      second trimester, abnormalities are revealed on ultrasound, mainly Turner
      syndrome in full or mosaic form and 47,XYY.

PMID- 24445235
TI  - Umbilical vein volume flow in monochorionic twin pairs at 11-14 weeks.
AB  - We investigated the umbilical vein volume flow (UVVF) at 11-14 weeks in
      monochorionic-diamniotic (MCDA) twins, focusing on the occurrence of
      complications. We considered 87 MCDA pregnancies. We used "E-flow" to detect the
      umbilical vein and measured the mean velocities and diameters of veins, also
      calculating the UVVF. Pregnancies were divided into four groups: a (twin-to-twin
      transfusion, TTTS); b (selective intrauterine growth restriction, sIUGR); c
      (discordance of fluid, DF); and d (with "normal" outcome). The main outcome of
      the study was the assessment of the difference of UVVF between twin 1 and twin 2
      (larger and smaller twin). In eight of eight pairs of group a and seven of seven
      pairs of group b, the UVVF of fetuses 1 were significantly different than fetuses
      2 (P<0.05). The UVVFs of fetuses 2 of group a were significantly lower in respect
      to the UVVFs of fetuses 2 of group d (P<0.05). We provide evidence of an
      important difference in UVVF in pairs that successively developed TTTS or sIUGR.
      The smaller fetuses of group a (TTTS) showed a lower venous return than fetuses 2
      of group d (normal). First-trimester UVVF is lower in fetuses with a smaller
      crown-rump length in twin pairs at risk of TTTS or IUGR.

PMID- 24445236
TI  - Establishment of neurogenic microenvironment in the neurovascular unit: the
      connexin 43 story.
AB  - Connexins (Cx) play an important role in the coordination of intercellular
      communication, and autocrine and paracrine regulation of cells within the
      neurovascular unit (NVU). Gap junctional mechanisms control proliferation and
      differentiation processes underlying neurogenesis and angiogenesis in the brain.
      Cx43 possesses some unique properties [the ability to form either intercellular
      channels permeable for regulatory molecules and ions or hemichannels open to the
      extracellular space to provide release of cell metabolites; functional coupling
      with nicotinamide adenine dinucleotide (NAD+)-consuming and NAD+-dependent
      enzymatic processes] which may be of great importance for the fate of the stem
      cells. Dynamic changes in Cx43 expression are associated with different stages of
      brain cells development either at embryonic or adult periods of ontogenesis. This
      review summarizes recent data on Cx43-controlled neurogenesis in the context of
      NVU development and functioning. Understanding the molecular mechanisms of gap
      junctional intercellular communication will support translational studies focused
      on the development of regeneration-based approaches for the therapy of central
      nervous system pathology.

PMID- 24445237
TI  - Citrate--new functions for an old metabolite.
AB  - Citrate is an important substrate in cellular energy metabolism. It is produced
      in the mitochondria and used in the Krebs cycle or released into cytoplasm
      through a specific mitochondrial carrier, CIC. In the cytosol, citrate and its
      derivatives, acetyl-CoA and oxaloacetate, are used in normal and pathological
      processes. Beyond the classical role as metabolic regulator, recent studies have
      highlighted that citrate is involved in inflammation, cancer, insulin secretion,
      histone acetylation, neurological disorders, and non-alcoholic fatty liver
      disease. Monitoring changes in the citrate levels could therefore potentially be
      used as diagnostic tool. This review highlights these new aspects of citrate
      functions.

PMID- 24445238
TI  - Analytical evaluation of the automated galectin-3 assay on the Abbott ARCHITECT
      immunoassay instruments.
AB  - BACKGROUND: Galectin-3 is secreted from macrophages and binds and activates
      fibroblasts forming collagen. Tissue fibrosis is central to the progression of
      chronic heart failure (CHF). We performed a European multicentered evaluation of
      the analytical performance of the two-step routine and Short Turn-Around-Time
      (STAT) galectin-3 immunoassay on the ARCHITECT i1000SR, i2000SR, and i4000SR
      (Abbott Laboratories). METHODS: We evaluated the assay precision and dilution
      linearity for both routine and STAT assays and compared serum and plasma, and
      fresh vs. frozen samples. The reference interval and biological variability were
      also assessed. Measurable samples were compared between ARCHITECT instruments and
      between the routine and STAT assays and also to a galectin-3 ELISA (BG Medicine).
      RESULTS: The total assay coefficient of variation (CV%) was 2.3%-6.2% and 1.7%
      7.4% for the routine and STAT assays, respectively. Both assays demonstrated
      linearity up to 120 ng/mL. Galectin-3 concentrations were higher in plasma
      samples than in serum samples and correlated well between fresh and frozen
      samples (R=0.997), between the routine and STAT assays, between the ARCHITECT
      i1000 and i2000 instruments and with the galectin-3 ELISA. The reference interval
      on 627 apparently healthy individuals (53% male) yielded upper 95th and 97.5th
      percentiles of 25.2 and 28.4 ng/mL, respectively. Values were significantly lower
      in subjects younger than 50 years. CONCLUSIONS: The galectin-3 routine and STAT
      assays on the Abbott ARCHITECT instruments demonstrated good analytical
      performance. Further clinical studies are required to demonstrate the diagnostic
      and prognostic potential of this novel marker in patients with CHF.

PMID- 24445239
TI  - High prevalence of anti-thyroid antibodies associated with a low vitamin D status
      in a pediatric cohort.

PMID- 24445240
TI  - Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide 2
      antibody and anti-cyclic citrullinated peptide 3 antibody in rheumatoid
      arthritis.
AB  - The aim of this work was to assess the diagnostic value of anti-CCP-3 and anti
      CCP-2 for the diagnosis of rheumatoid arthritis (RA) and determine whether anti
      CCP-3 more accurately identifies patients with rheumatoid arthritis than anti-CCP
      2. PubMed and CNKI databases were searched for studies published in English and
      Chinese that examined the use of anti-CCP-3 and anti-CCP-2 in the diagnosis of
      known or suspected rheumatoid arthritis from January 2006 to July 2013. Seventeen
      included studies of methodological quality were rated by using the Quality
      Assessment of Diagnostic Accuracy Studies (QUADAS) tools A random-effects method
      was used to summarize sensitivities, specificities, positive and negative
      likelihood ratio (LR+ and LR-, respectively), and diagnostic odds ratio from 17
      studies. The pooled sensitivity, specificity, LR+, LR- and diagnostic odds ratio
      for anti-CCP-3 were 0.737 (95% CI, 0.717-0.757), 0.933 (95% CI, 0.924-0.942),
      11.096 (95% CI, 8.876-13.870), 0.274 (95% CI, 0.231-0.326), and 42.908 (95% CI,
      33.828-54.426), respectively. For anti-CCP-2, the values were 0.719 (95% CI,
      0.699-0.739), 0.960 (95% CI, 0.953-0.966), 17.485 (95% CI, 11.960-25.562), 0.294
      (95% CI, 0.258-0.335) and 63.458 (95% CI, 44.214-91.078), respectively. With high
      specificity and moderate sensitivity, anti-CCP-2 and anti-CCP-3 played an
      important role in confirming the diagnosis of RA. Anti-CCP-3 did not have better
      diagnostic performances than anti-CCP-2, but anti-CCP-2 had evident heterogeneity
      compared to anti-CCP-3, especially in American patients.

PMID- 24445241
TI  - Vitamin D, atopy, immunity.

PMID- 24445242
TI  - Quantification of teicoplanin in plasma by LC-MS with online sample clean-up and
      comparison with QMS assay.
AB  - BACKGROUND: Teicoplanin is a glycopeptide antibiotic used for the treatment of
      infections caused by Gram-positive bacteria. There is a good correlation between
      trough levels and clinical outcome, therefore therapeutic drug monitoring is
      recommended. Here we present a liquid chromatography-mass spectrometry (LC-MS)
      method with online extraction based on turbulent flow chromatography for the
      quantification of the five main components of teicoplanin, A2-1, A2-2, A2-3, A2
      4, and A2-5. METHODS: After online extraction, analytical chromatography was
      performed on a Hypersil Gold C8 column under acidic conditions. As mass
      spectrometer, a Q Exactive hybrid instrument was used. Samples were prepared by
      adding internal standard and subsequent centrifugation. Patient samples (n=125)
      that had previously been analyzed using a commercially available immunoassay (QMS
      teicoplanin) were re-analyzed by LC-MS. RESULTS: The imprecision was <6.9%,
      inaccuracy between 99.6% and 109%, for both, within- and between-day analysis.
      The method was shown to be free of matrix effects in the relevant time ranges and
      was compared to a commercially available immunoassay, QMS(r) teicoplanin from
      Thermo Fisher Scientific. The LC-MS assay produced comparable results to the QMS
      assay, the correlation coefficient was 0.856 (95% confidence interval 0.800
      0.896). LC-MS yielded lower concentrations than the immunoassay as could be
      demonstrated by the bias of -1.16 mg/L (95% confidence interval -1.90-0.43 mg/L)
      in the Bland-Altman analysis. CONCLUSIONS: This specific, automated, LC-MS assay
      for teicoplanin is suitable for therapeutic drug monitoring.

PMID- 24445243
TI  - Characterization of a complex CYP2D6 genotype that caused an AmpliChip CYP450
      Test no-call in the clinical setting.
AB  - BACKGROUND: CYP2D6, a major drug-metabolizing enzyme, is encoded by a highly
      polymorphic and complex gene locus. We have identified a patient who failed to
      produce a CYP2D6 genotype with the AmpliChip P450 Test (AmpliChip), whereas his
      CYP2C19 genotype was readily determined. The aim of this investigation was to
      fully characterize the patient's CYP2D6 gene locus to resolve the AmpliChip no
      call. METHODS: The case, a brother, and son were genotyped with the AmpliChip and
      subsequently characterized using long-range (XL)-PCR coupled with TaqMan assay
      technology. Copy number variation was assessed by XL-PCR and quantitative PCR.
      Selected XL-PCR products were sequenced. RESULTS: The AmpliChip also produced a
      no-call for the son; the brother produced a result. The two alleles of the case
      were subsequently found to carry additional gene units that likely caused the
      AmpliChip no-calls. One was characterized as a CYP2D6*68+*4 tandem (CYP2D6*68 is
      a hybrid gene composed of 2D6 and 2D7), the other as a rare CYP2D6*13+*2 tandem
      (CYP2D6*13 is a 2D7/2D6 hybrid formerly known as CYP2D6*77). A novel CYP2D6*2
      subvariant was identified in the son; the brother also carried the CYP2D6*68+*4
      tandem. CONCLUSIONS: The implementation of pharmacogenetics-guided drug therapy
      relies on accurate clinical-grade genotype analysis. Although the AmpliChip is
      deemed to be a reliable platform, numerous more recently discovered allelic
      variants and gene arrangements are not detected or trigger no-calls. Although
      such cases may be rare, the clinical/genetic testing community must be aware of
      the challenges of CYP2D6 testing on the AmpliChip platform and implications
      regarding accuracy of test results.

PMID- 24445244
TI  - The effect of error-in-confounders on the estimation of the causal parameter when
      using marginal structural models and inverse probability-of-treatment weights: a
      simulation study.
AB  - We performed an empirical study to evaluate the effect of mismeasured continuous
      confounders on the estimation of the causal parameter when using marginal
      structural models and inverse probability-of-treatment weighting. By executing an
      extensive simulation using 500 randomly generated parameter value combinations
      within a defined space, we observed the well-understood effects of attenuation
      and augmentation, and two unanticipated effects: null effects and sign reversals.
      We implemented a secondary empirical study to further investigate the sign
      reversal effect. We use the results of our study to identify conceptual
      similarities between the analytic and empirical results for multivariable linear
      and logistic regression, and our empirical results. Through this synthesis, we
      have been able to suggest feasible directions of research as well as outline the
      form of expected results.

PMID- 24445245
TI  - [Efficacy of aripiprazole for the treatment of schizophrenia: what dose is
      required?].
AB  - OBJECTIVE: Problem of the choice of antipsychotic dose is a key issue in clinical
      practice. It determines the efficacy and safety of treatment. Aripiprazole is
      recommended at a dose of between 10 and 15 mg/day in the treatment of
      schizophrenia, with a dose range considered to be effective, between 10 and 30
      mg/day. This wide therapeutic range prompted us to investigate the existence of a
      possible dose-effect relationship for aripiprazole in the treatment of
      schizophrenia. METHOD: We conducted a literature review from PubMed and EMBASE
      database, with the keywords: aripiprazole, schizophrenia. We limited it to
      studies published in English and French, with the main objective to assess the
      efficacy of aripiprazole in patients with schizophrenia. We selected only
      randomized clinical trials, double-blind, controlled against placebo or against
      an active comparator. Studies in which aripiprazole was studied added to another
      antipsychotic were not retained. RESULTS: Twenty-two randomized, double-blind,
      controlled studies were selected. Three studies assessed the efficacy of
      aripiprazole on agitation symptoms in patients with schizophrenia and for which a
      dose of aripiprazole between 1 and 15mg showed significant efficacy compared to
      placebo. Seven clinical trials focused on the effect of aripiprazole short term
      (less than 12weeks). For the primary endpoint (PANSS scores), aripiprazole was
      superior to placebo or equivalent to active comparators (risperidone, olanzapine
      or haloperidol). These short-term studies revealed a range of effective doses
      from 10 mg/day to 20 mg/day. Five studies, lasting between 16 and 52 weeks, with
      a primary endpoint being the time to discontinuation for any cause for two
      studies, the time before relapse in one study, and the improvement in PANSS
      scores for the two other studies. On these different endpoints, aripiprazole was
      effective at average doses between 15 and 28.1 mg/day. The safety of aripiprazole
      was particularly favourable in these trials. Finally, we listed seven post-hoc
      analyses. In support of these long-term analyses on different endpoints,
      aripiprazole showed significant efficacy at higher doses (20 and 30 mg/day) than
      those used in the agitation treatment. CONCLUSIONS: No study was designed to
      compare aripiprazole doses in schizophrenia. Nevertheless, efficacy on agitation
      and hostility components had been observed for doses of 10mg/day, or lower;
      whereas the antipsychotic effect in acute or maintenance phase appeared optimal
      for doses ranging from 10 to 25 mg/day. Only one study retained a minimum
      effective dose of 10mg/day on the PANSS scores. This literature review reveals an
      effective dose range between 10 and 25 mg/day for aripiprazole in schizophrenia.
      Less than 10 mg/day did not show significant efficacy on symptoms of
      schizophrenia, apart from a specific short-term effect on agitation, at very low
      doses (starting at 1mg). Optimization of treatment, at doses above 25 mg/day,
      cannot be the subject of evidence-based recommendations.

PMID- 24445248
TI  - Transnasal endoscopic treatment of bilateral choanal atresia in newborns using
      balloon dilatation: own results and review of literature.
AB  - OBJECTIVES: Congenital choanal atresia is a complete obliteration of the
      posterior nasal aperture leading to life-threatening airway emergencies. Several
      surgical options including sublabial, transpalatal, transseptal or external
      approaches have been developed for the repair of choanal atresia. So far, no gold
      standard has been established, but transnasal endoscopic approaches have been
      favored by many surgeons in recent years. METHODS: Since 2008 a standard
      procedure for bilateral choanal atresia repair in neonates using an endoscopic
      transnasal approach supported by balloon dilatation has been established at the
      Department of Otorhinolaryngology at Ulm University Medical Center. During the
      last five years, six cases of bilateral choanal atresia were diagnosed and
      treated, including two male and four female patients aged between three days and
      two months, at the date of surgery. All interventions were performed in
      transnasal endoscopic technique. In all patients the abnormally thick posterior
      vomer and the atretic bony plate were resected and the mucosa was perforated. A
      balloon dilator was used to dilate the neochoanae and prevent restenosis. All six
      patients were intraoperatively stented for at least six weeks. RESULTS: All six
      neonates with bilateral choanal atresia, who were operated in endoscopic
      transnasal technique had patent neo-choanae on both sides. No severe
      postoperative complications were found. The number of revisions depends on the
      age at primary surgery. CONCLUSIONS: Endonasal endoscopic approach and balloon
      dilatation is a safe, reproducible technique for surgical repair of choanal
      atresia. We recommend the use of bilateral stents, especially in very young
      patients, as a prerequisite to prevent early restenosis.

PMID- 24445247
TI  - Upper airway cough syndrome in children and two inflammatory factors: TRPV1 and
      TGF-beta2.
AB  - OBJECTIVES: The aim of the study was to investigate upper airway cough syndrome
      (UACS) in children and to determine alternative methods to explore the
      relationships among TRPV1, TGF-beta2, and UACS. METHODS: In 2012, 104 children
      with adenoid hypertrophy aged 2-13 years who were admitted to the otolaryngology
      department, Capital Institute of Pediatrics-affiliated children's hospital, were
      included in this study. Enzyme-linked immunosorbent assay (ELISA) and
      immunohistochemical (IHC) studies for TRPV1 and TGF-beta2 were performed to
      understand the relationship between the two inflammatory factors, and the
      correlations among the indices and UACS. The research was divided into three
      stages. In stage 1, 72 children (24 UACS and 48 controls) were enrolled in the
      study, and ELISAs for TRPV1 and TGF-beta2 were performed. In stage 2, 32 children
      (16 UACS and 16 controls) were enrolled in the study and both ELISA and IHC for
      TRPV1 and TGF-beta2 were performed. In stage 3, 41 children were enrolled in this
      research who had thick mucus secretions in the posterior nasal apertures in stage
      1 and 2 (23 cases with chief complaint (or history) of chronic cough and 18 cases
      without). The difference between the TRPV1 and TGF-beta2 serum values and the
      clinical factors was determined. RESULTS: The levels of TRPV1 and TGF-beta2 were
      significantly increased in the UACS cases. OSAHS and thick mucus secretions
      correlated with a diagnosis of UACS. A history of asthma and thick mucus
      secretions correlated with elevation of the two inflammatory factors. There was
      no statistical correlation between ELISA and IHC testing. Among the children with
      thick mucus secretions, some had a higher possibility of chronic coughing
      including those who had higher levels of the two indices, larger tonsils and a
      history of chronic tonsillitis. CONCLUSION: The detections of TRPV1 and TGF-beta2
      from serum and adenoid body specimens are valuable for UACS auxiliary diagnosis.
      Tonsil hypertrophy and chronic tonsillitis history are independent risk factors
      of UACS.

PMID- 24445249
TI  - Extensive necrotizing fasciitis associated with sunitinib therapy.

PMID- 24445250
TI  - Less satisfaction with information in patients with prostate cancer treated with
      surgery and salvage radiotherapy compared with patients treated with curative
      radiotherapy alone, despite similar health-related quality of life.
AB  - BACKGROUND: This study examined patient perception of information received,
      satisfaction with that information, and its relation to health-related quality of
      life (HRQoL) and clinical and demographic variables before, during, and after
      radiotherapy (RT) for localized prostate cancer. PATIENTS AND METHODS: In 2010, 2
      questionnaires (European Organisation for Research and Treatment of Cancer
      Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and EORTC QLQ information
      module [QLQ-INFO25]) were sent to 660 consecutive patients with prostate cancer
      who had undergone or were to undergo RT with curative intent between December
      2006 and March 2010. RESULTS: The response rate was 92%. Although most patients
      (69%) were satisfied with the information they received, statistically
      significant differences were found for all but 2 EORTC QLQ-INFO25 variables,
      favoring those who were treated with RT alone compared with those treated with
      both prostatectomy and salvage RT. Statistically significant associations between
      all HRQoL variables and satisfaction with information were found; higher levels
      of satisfaction were associated with better functioning and lower levels of
      symptoms and problems. CONCLUSION: Satisfaction with the information received was
      studied in patients with prostate cancer with localized disease. Despite the fact
      that the majority of patients reported being satisfied with the information
      received, there is room for improvement, especially regarding "the disease,"
      "other services," "different places of care," and "things you can do to help
      yourself." Patients treated with both prostatectomy and salvage RT reported
      significantly lower levels of satisfaction with information received and of
      having received significantly less information than did patients treated with RT
      alone.

PMID- 24445246
TI  - The functions of cardiolipin in cellular metabolism-potential modifiers of the
      Barth syndrome phenotype.
AB  - The phospholipid cardiolipin (CL) plays a role in many cellular functions and
      signaling pathways both inside and outside of mitochondria. This review focuses
      on the role of CL in energy metabolism. Many reactions of electron transport and
      oxidative phosphorylation, the transport of metabolites required for these
      processes, and the stabilization of electron transport chain supercomplexes
      require CL. Recent studies indicate that CL is required for the synthesis of iron
      sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways.
      Activation of carnitine shuttle enzymes that are required for fatty acid
      metabolism is CL dependent. The presence of substantial amounts of CL in the
      peroxisomal membrane suggests that CL may be required for peroxisomal functions.
      Understanding the role of CL in energy metabolism may identify physiological
      modifiers that exacerbate the loss of CL and underlie the variation in symptoms
      observed in Barth syndrome, a genetic disorder of CL metabolism. 

PMID- 24445251
TI  - Wistar rats from different suppliers have a different response in an acute
      myocardial infarction model.
AB  - The Wistar rat is a commonly used strain for experimental animal models. Recently
      it was shown that results vary between studies using Wistar rats of different
      suppliers. Therefore we studied whether Wistar rats obtained from Harlan
      Laboratories (Ha, n=24) and Charles River (CR, n=22) had a different outcome in
      an acute myocardial infarction (AMI) model. AMI was induced in both Ha and CR
      Wistar rats by one operator. This resulted in a significantly higher survival
      rate for Ha (79.2+/-10.2%) compared with CR rats (54.2+/-10.2%, p<0.05).
      Furthermore, CR rats had lost significantly more weight after 7 days (-5.9+/
      3.1%) compared with Ha rats (-0.8+/-1.7%; p<0.001), indicating a worse health
      status of the CR rats. Paradoxically, the induced infarct was smaller in CR rats
      (7.3+/-3.6% of the heart) compared with Ha rats (12.1+/-4.7%, p<0.05). This
      indicates that CR rats were less sensitive for the cardiomyocyte damage
      subsequent to AMI induction, but remarkably showed more clinical side effects
      indicating that Wistar rats from two suppliers had a different response within
      the same AMI model.

PMID- 24445252
TI  - In vivo metabolic flux profiling with stable isotopes discriminates sites and
      quantifies effects of mitochondrial dysfunction in C. elegans.
AB  - Mitochondrial respiratory chain (RC) disease diagnosis is complicated both by an
      absence of biomarkers that sufficiently divulge all cases and limited capacity to
      quantify adverse effects across intermediary metabolism. We applied high
      performance liquid chromatography (HPLC) and mass spectrometry (MS) studies of
      stable-isotope based precursor-product relationships in the nematode, C. elegans,
      to interrogate in vivo differences in metabolic flux among distinct genetic
      models of primary RC defects and closely related metabolic disorders. METHODS: C.
      elegans strains studied harbor single nuclear gene defects in complex I, II, or
      III RC subunits (gas-1, mev-1, isp-1); enzymes involved in coenzyme Q
      biosynthesis (clk-1), the tricarboxylic acid cycle (TCA, idh-1), or pyruvate
      metabolism (pdha-1); and central nodes of the nutrient-sensing signaling network
      that involve insulin response (daf-2) or the sirtuin homologue (sir-2.1).
      Synchronous populations of 2000 early larval stage worms were fed standard
      Escherichia coli on nematode growth media plates containing 1,6-(13)C2-glucose
      throughout their developmental period, with samples extracted on the first day of
      adult life in 4% perchloric acid with an internal standard. Quantitation of whole
      animal free amino acid concentrations and isotopic incorporation into amino and
      organic acids throughout development was performed in all strains by HPLC and
      isotope ratio MS, respectively. GC/MS analysis was also performed to quantify
      absolute isotopic incorporation in all molecular species of key TCA cycle
      intermediates in gas-1 and N2 adult worms. RESULTS: Genetic mutations within
      different metabolic pathways displayed distinct metabolic profiles. RC complex I
      (gas-1) and III (isp-1) subunit mutants, together with the coenzyme Q
      biosynthetic mutant (clk-1), shared a similar amino acid profile of elevated
      alanine and decreased glutamate. The metabolic signature of the complex II mutant
      (mev-1) was distinct from that of the other RC mutants but resembled that of the
      TCA cycle mutant (idh-1) and both signaling mutants (daf-2 and sir-2.1). All
      branched chain amino acid levels were significantly increased in the complex I
      and III mutants but decreased in the PDH mutant (pdha-1). The RC complex I,
      coenzyme Q, TCA cycle, and PDH mutants shared significantly increased relative
      enrichment of lactate+1 and absolute concentration of alanine+1, while
      glutamate+1 enrichment was significantly decreased uniquely in the RC mutants.
      Relative intermediary flux analyses were suggestive of proximal TCA cycle
      disruption in idh-1, completely reduced TCA cycle flux in sir-2.1, and apparent
      distal TCA cycle alteration in daf-2. GC/MS analysis with universally-labeled
      (13)C-glucose in adult worms further showed significantly increased isotopic
      enrichment in lactate, citrate, and malate species in the complex I (gas-1)
      mutant. CONCLUSIONS: Stable isotopic/mass spectrometric analysis can sensitively
      discriminate primary RC dysfunction from genetic deficiencies affecting either
      the TCA cycle or pyruvate metabolism. These data are further suggestive that
      metabolic flux analysis using stable isotopes may offer a robust means to
      discriminate and quantify the secondary effects of primary RC dysfunction across
      intermediary metabolism.

PMID- 24445254
TI  - Combined inhibition of morphogen pathways demonstrates additive antifibrotic
      effects and improved tolerability.
AB  - OBJECTIVES: The morphogen pathways Hedgehog, Wnt and Notch are attractive targets
      for antifibrotic therapies in systemic sclerosis. Interference with stem cell
      regeneration, however, may complicate the use of morphogen pathway inhibitors. We
      therefore tested the hypothesis that combination therapies with low doses of
      Hedgehog, Wnt and Notch inhibitors maybe safe and effective for the treatment of
      fibrosis. METHODS: Skin fibrosis was induced by bleomycin and by overexpression
      of a constitutively active TGF-beta receptor type I. Adverse events were assessed
      by clinical monitoring, pathological evaluation and quantification of Lgr5
      positive intestinal stem cells. RESULTS: Inhibition of Hedgehog, Wnt and Notch
      signalling dose-dependently ameliorated bleomycin-induced and active TGF-beta
      receptor type I-induced fibrosis. Combination therapies with low doses of
      Hedgehog/Wnt inhibitors or Hedgehog/Notch inhibitors demonstrated additive
      antifibrotic effects in preventive as well as in therapeutic regimes. Combination
      therapies were well tolerated. In contrast with high dose monotherapies,
      combination therapies did not reduce the number of Lgr5 positive intestinal stem
      cells. CONCLUSIONS: Combined inhibition of morphogen pathways exerts additive
      antifibrotic effects. Combination therapies are well tolerated and, in contrast
      to high dose monotherapies, may not impair stem cell renewal. Combined targeting
      of morphogen pathways may thus help to overcome dose-limiting toxicity of
      Hedgehog, Wnt and Notch signalling.

PMID- 24445253
TI  - SAMHD1 prevents autoimmunity by maintaining genome stability.
AB  - OBJECTIVES: The HIV restriction factor, SAMHD1 (SAM domain and HD domain
      containing protein 1), is a triphosphohydrolase that degrades deoxyribonucleoside
      triphosphates (dNTPs). Mutations in SAMHD1 cause Aicardi-Goutieres syndrome
      (AGS), an inflammatory disorder that shares phenotypic similarity with systemic
      lupus erythematosus, including activation of antiviral type 1 interferon (IFN).
      To further define the pathomechanisms underlying autoimmunity in AGS due to
      SAMHD1 mutations, we investigated the physiological properties of SAMHD1.
      METHODS: Primary patient fibroblasts were examined for dNTP levels,
      proliferation, senescence, cell cycle progression and DNA damage. Genome-wide
      transcriptional profiles were generated by RNA sequencing. Interaction of SAMHD1
      with cyclin A was assessed by coimmunoprecipitation and fluorescence cross
      correlation spectroscopy. Cell cycle-dependent phosphorylation of SAMHD1 was
      examined in synchronised HeLa cells and using recombinant SAMHD1. SAMHD1 was
      knocked down by RNA interference. RESULTS: We show that increased dNTP pools due
      to SAMHD1 deficiency cause genome instability in fibroblasts of patients with
      AGS. Constitutive DNA damage signalling is associated with cell cycle delay,
      cellular senescence, and upregulation of IFN-stimulated genes. SAMHD1 is
      phosphorylated by cyclin A/cyclin-dependent kinase 1 in a cell cycle-dependent
      manner, and its level fluctuates during the cell cycle, with the lowest levels
      observed in G1/S phase. Knockdown of SAMHD1 by RNA interference recapitulates
      activation of DNA damage signalling and type 1 IFN activation. CONCLUSIONS:
      SAMHD1 is required for genome integrity by maintaining balanced dNTP pools. dNTP
      imbalances due to SAMHD1 deficiency cause DNA damage, leading to intrinsic
      activation of IFN signalling. These findings establish a novel link between DNA
      damage signalling and innate immune activation in the pathogenesis of
      autoimmunity.

PMID- 24445255
TI  - The specificity of ultrasound-detected bone erosions for rheumatoid arthritis.
AB  - BACKGROUND: Bone erosion is one of the hallmarks of rheumatoid arthritis (RA),
      but also seen in other rheumatic diseases. The objective of this study was to
      determine the specificity of ultrasound (US)-detected bone erosions (including
      their size) in the classical 'target' joints for RA. METHODS: Patients fulfilling
      the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in
      addition to healthy volunteers were included. The following areas were examined
      by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd
      and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP)
      joints. All joints were scanned in four quadrants using both semiquantitative (0
      3) and quantitative (erosion diameter) scoring systems. RESULTS: 310 subjects
      were recruited. The inter-reader and intrareader agreements were good to
      excellent. US-detected bone erosions were more frequent but not specific for RA
      (specificity 32.9% and sensitivity 91.4%). The presence of erosions with
      semiquantitative score >=2 in four target joints (2nd, 5rd MCP, 5th MTP joints
      and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity
      41.4%). Size of erosion was found to be associated with RA. Erosions of any size
      in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4%
      and sensitivity 68.6%). CONCLUSIONS: The presence of US-detected erosions is not
      specific for RA. However, larger erosions in selected joints, especially 2nd and
      5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive
      of RA.

PMID- 24445256
TI  - Clinical evaluation of extracellular ADMA concentrations in human blood and
      adipose tissue.
AB  - Circulating asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of
      nitric oxide synthesis, has been proposed as a biomarker for clinical outcome.
      Dimethylarginine dimethylaminohydrolase (DDAH) is the main enzyme responsible for
      ADMA metabolism and elimination. Adipose tissue ADMA concentrations and DDAH
      activity and their role in diabetes and obesity have not yet been investigated.
      In this study, we evaluated clinical microdialysis in combination with a
      sensitive analytical method (GC-MS/MS) to measure ADMA concentrations in
      extracellular fluid. Adipose tissue ADMA concentrations were assessed before and
      during an oral glucose tolerance test in lean healthy subjects and subjects with
      diabetes (n = 4 each), and in morbidly obese subjects before and after weight
      loss of 30 kg (n = 7). DDAH activity was determined in subcutaneous and visceral
      adipose tissue obtained during laparoscopic surgery (n = 5 paired samples). Mean
      interstitial ADMA concentrations did not differ between study populations
      (healthy 0.17 +/- 0.03 uM; diabetic 0.21 +/- 0.03 uM; morbidly obese 0.16 +/-
      0.01 and 0.17 +/- 0.01 uM before and after weight loss, respectively). We did not
      observe any response of interstitial ADMA concentrations to the oral glucose
      challenge. Adipose tissue DDAH activity was negligible compared to liver tissue.
      Thus, adipose tissue ADMA plays a minor role in NO-dependent regulation of
      adipose tissue blood flow and metabolism. 

PMID- 24445257
TI  - Hispolon decreases melanin production and induces apoptosis in melanoma cells
      through the downregulation of tyrosinase and microphthalmia-associated
      transcription factor (MITF) expressions and the activation of caspase-3, -8 and 
      9.
AB  - Hispolon is one of the most important functional compounds that forms Phellinus
      linteus (Berkeley & Curtis) Teng. Hispolon has antioxidant, anti-inflammatory,
      antiproliferative and anticancer effects. In this study, we analyzed the
      functions of hispolon on melanogenesis and apoptosis in B16-F10 melanoma cells.
      The results demonstrated that hispolon is not an enzymatic inhibitor for
      tyrosinase; rather, it represses the expression of tyrosinase and the
      microphthalmia-associated transcription factor (MITF) to reduce the production of
      melanin in alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated B16-F10
      cells at lower concentrations (less than 2 MUM). In contrast, at higher
      concentration (greater than 10 MUM), hispolon can induce activity of caspase-3, 
      8 and -9 to trigger apoptosis of B16-F10 cells but not of Detroit 551 normal
      fibroblast cells. Therefore, we suggest that hispolon has the potential to treat
      hyperpigmentation diseases and melanoma skin cancer in the future. 

PMID- 24445259
TI  - Synthesis and antimicrobial evaluation of some novel thiazole, pyridone,
      pyrazole, chromene, hydrazone derivatives bearing a biologically active
      sulfonamide moiety.
AB  - This study aimed for the synthesis of new heterocyclic compounds incorporating
      sulfamoyl moiety suitable for use as antimicrobial agents via a versatile,
      readily accessible N-[4-(aminosulfonyl)phenyl]-2-cyanoacetamide (3). The 2
      pyridone derivatives were obtained via reaction of cyanoacetamide with
      acetylacetone or arylidenes malononitrile. Cycloaddition reaction of
      cyanoacetamide with salicyaldehyde furnished chromene derivatives. Diazotization
      of 3 with the desired diazonium chloride gave the hydrazone derivatives 13a-e.
      Also, the reactivity of the hydrazone towards hydrazine hydrate to give Pyrazole
      derivatives was studied. In addition, treatment of 3 with elemental sulfur and
      phenyl isothiocyanate or malononitrile furnished thiazole and thiophene
      derivatives respectively. Reaction of 3 with phenyl isothiocyanate and KOH in DMF
      afforded the intermediate salt 17 which reacted in situ with 3-(2-bromoacetyl)-2H
      chromen-2-one and methyl iodide afforded the thiazole and ketene N,S-acetal
      derivatives respectively. Finally, reaction of 3 with carbon disulfide and 1,3
      dibromopropane afforded the N-[4-(aminosulfonyl) phenyl]-2-cyano-2-(1,3-dithian-2
      ylidene)acetamide product 22. All newly synthesized compounds were elucidated by
      considering the data of both elemental and spectral analysis. The compounds were
      evaluated for both their in vitro antibacterial and antifungal activities and
      showed promising results. 

PMID- 24445258
TI  - Neuroprotective strategies for traumatic brain injury: improving clinical
      translation.
AB  - Traumatic brain injury (TBI) induces secondary biochemical changes that
      contribute to delayed neuroinflammation, neuronal cell death, and neurological
      dysfunction. Attenuating such secondary injury has provided the conceptual basis
      for neuroprotective treatments. Despite strong experimental data, more than 30
      clinical trials of neuroprotection in TBI patients have failed. In part, these
      failures likely reflect methodological differences between the clinical and
      animal studies, as well as inadequate pre-clinical evaluation and/or trial design
      problems. However, recent changes in experimental approach and advances in
      clinical trial methodology have raised the potential for successful clinical
      translation. Here we critically analyze the current limitations and translational
      opportunities for developing successful neuroprotective therapies for TBI. 

PMID- 24445260
TI  - The bioconcentration and degradation of nonylphenol and nonylphenol
      polyethoxylates by Chlorella vulgaris.
AB  - Nonylphenol polyethoxylates (NPnEOs), a major class of nonionic surfactants, can
      easily enter into aquatic environments through various pathways due to their wide
      applications, which leads to the extensive existence of their relative stable
      metabolites, namely nonylphenol (NP) and mono- to tri-ethoxylates. This study
      investigated the bioconcentration and degradation of NP and NPnEO oligomers (n =
      1-12) by a green algae, Chlorella vulgaris. Experimental results showed that C.
      vulgaris can remove NP from water phase efficiently, and bioconcentration and
      degradation accounted for approximately half of its loss, respectively, with a 48
      h BCF (bioconcentration factor) of 2.42 * 10(3). Moreover, C. vulgaris could
      concentrate and degrade NPnEOs, distribution profiles of the series homologues of
      the NPnEOs in algae and water phase were quite different from the initial
      homologue profile. The 48 h BCF of the NPnEO homologues increased with the length
      of the EO chain. Degradation extent of total NPnEOs by C. vulgaris was 95.7%, and
      only 1.1% remained in water phase, and the other 3.2% remained in the algal
      cells. The algae removed the NPnEOs mainly through degradation. Due to rapid
      degradation, concentrations of the long chain NPnEO homologous in both water (n
      >= 2) and the algal phase (n >= 5) was quite low at the end of a 48 h experiment.

PMID- 24445262
TI  - Rapid and efficient functionalized ionic liquid-catalyzed aldol condensation
      reactions associated with microwave irradiation.
AB  - Five quaternary ammonium ionic liquid (IL) and two tetrabutylphosphonium ILs were
      prepared and characterized. An environmentally benign and convenient
      functionalized ionic liquid catalytic system was thus explored in the aldol
      condensation reactions of aromatic aldehydes with acetone. The aldol reactions
      proceeded more efficiently through microwave-assisted heating than through
      conventional thermal heating. The yield of products obtained under microwave
      heating for 30 min was approximately 90%, and the ILs can be recovered and reused
      at least five times without apparent loss of activity. In addition, this
      catalytic system can be successfully extended to the Henry reactions. 

PMID- 24445261
TI  - Re-evaluation of binding properties of recombinant lymphocyte receptors NKR-P1A
      and CD69 to chemically synthesized glycans and peptides.
AB  - The binding of monosaccharides and short peptides to lymphocyte receptors (human
      CD69 and rat NKR-P1A) was first reported in 1994 and then in a number of
      subsequent publications. Based on this observation, numerous potentially high
      affinity saccharide ligands have been synthesized over the last two decades in
      order to utilize their potential in antitumor therapy. Due to significant
      inconsistencies in their reported binding properties, we decided to re-examine
      the interaction between multiple ligands and CD69 or NKR-P1A. Using NMR titration
      and isothermal titration calorimetry we were unable to detect the binding of the
      tested ligands such as N-acetyl-D-hexosamines and oligopeptides to both
      receptors, which contradicts the previous observations published in more than
      twenty papers over the last fifteen years.

PMID- 24445263
TI  - Elevations in time-varying resting heart rate predict subsequent all-cause
      mortality in older adults.
AB  - BACKGROUND: An increased resting heart rate (RHR) has long been associated with
      unhealthy life. Nevertheless, it remains uncertain whether time-varying
      measurements of RHR are predictive of mortality in older persons. DESIGN: The
      purpose of this study was to assess the relationship between repeated
      measurements of RHR and risk of death from all causes among older adults.
      METHODS: We evaluated repeat measurements of resting heart rate among 5691 men
      and women (aged 65 years or older) enrolled in the Cardiovascular Health Study.
      RHR was measured annually for six consecutive years by validated
      electrocardiogram. All-cause mortality was confirmed by a study-wide Mortality
      Review Committee using reviews of obituaries, death certificates and hospital
      records, interviews with attending physicians, and next-of-kin. RESULTS: Of the
      study cohort, 974 (17.1%) participants died. Each 10 beat/min increment in RHR
      increased the risk of death by 33% (adjusted hazard ratio, 95% confidence
      interval (CI) = 1.33, 1.26-1.40). Similar results were observed (adjusted hazard
      ratio, 95% CI = 2.21, 1.88-2.59) when comparing the upper-most quartile of RHR
      (mean = 81 beats/min) with the lowest (mean = 53 beats/min). Compared with
      participants whose RHR was consistently <=65 beats/min during the study period,
      the risk of death increased monotonically for each 10 beat/min (consistent)
      increment in RHR, with adjusted hazard ratios (95% CI) ranging from 1.30 (1.23
      1.37) for 75 beats/min to 4.78 (3.49-6.52) for 125 beats/min. CONCLUSIONS:
      Elevations in the RHR over the course of six years are associated with an
      increased risk of all-cause mortality among older adults.

PMID- 24445264
TI  - The importance of upright posture in exercise testing and training for patients
      with hypertrophic cardiomyopathy.

PMID- 24445265
TI  - Anisotropic energy flow and allosteric ligand binding in albumin.
AB  - Allosteric interactions in proteins generally involve propagation of local
      structural changes through the protein to a remote site. Anisotropic energy
      transport is thought to couple the remote sites, but the nature of this process
      is poorly understood. Here, we report the relationship between energy flow
      through the structure of bovine serum albumin and allosteric interactions between
      remote ligand binding sites of the protein. Ultrafast infrared spectroscopy is
      used to probe the flow of energy through the protein backbone following
      excitation of a heater dye, a metalloporphyrin or malachite green, bound to
      different binding sites in the protein. We observe ballistic and anisotropic
      energy flow through the protein structure following input of thermal energy into
      the flexible ligand binding sites, without local heating of the rigid helix
      bundles that connect these sites. This efficient energy transport mechanism
      enables the allosteric propagation of binding energy through the connecting helix
      structures. 

PMID- 24445266
TI  - Induced pluripotent stem cell-derived myeloid phagocytes: disease modeling and
      therapeutic applications.
AB  - Myeloid phagocytes (neutrophils, monocytes, macrophages and dendritic cells) have
      key roles in immune defense, as well as in tissue repair and remodeling.
      Defective or dysregulated myeloid phagocyte production or function can cause
      immune dysfunction, blood cell malignancies and inflammatory diseases. The tumor
      microenvironment can also condition myeloid phagocytes to promote tumor growth.
      Studies of their physiological and pathophysiological roles and the mechanisms
      regulating their production and function are crucial for the identification of
      novel therapeutic targets. In this review, we examine the use of induced
      pluripotent stem cells to study myeloid phagocytes in human diseases and develop
      future therapeutic strategies. 

PMID- 24445268
TI  - Use of 111In-pentetreotide scan in a subject with treatment refractory atypical
      meningioma.
AB  - A 57-year-old man with a history of multiple recurrent atypical meningiomas
      (World Health Organization grade II) had several surgical resections including
      gamma knife resection of the parafalcine meningioma, followed with a stereotactic
      radiosurgical ablation. Despite these treatments, an MRI scan performed 7 months
      later showed progression of the disease. The patient remained symptomatic with
      intermittent severe headaches associated with nausea, vomiting, and visual
      disturbance. He had a positive In-pentetreotide indicating the presence of
      somatostatin receptors. Therefore, he was placed on systemic Sandostatin
      (octreotide acetate) treatment, and at follow-up, he was clinically responsive to
      treatment. 

PMID- 24445267
TI  - Role of BRD4 in hematopoietic differentiation of embryonic stem cells.
AB  - The bromodomain and extra terminal (BET) protein family member BRD4 is a
      transcriptional regulator, critical for cell cycle progression and cellular
      viability. Here, we show that BRD4 plays an important role in embryonic stem cell
      (ESC) regulation. During differentiation of ESCs, BRD4 expression is upregulated
      and its gene promoter becomes demethylated. Disruption of BRD4 expression in ESCs
      did not induce spontaneous differentiation but severely diminished
      hematoendothelial potential. Although BRD4 regulates c-Myc expression, our data
      show that the role of BRD4 in hematopoietic commitment is not exclusively
      mediated by c-Myc. Our results indicate that BRD4 is epigenetically regulated
      during hematopoietic differentiation ESCs in the context of a still unknown
      signaling pathway. 

PMID- 24445269
TI  - Pituitary macroadenoma on 99mTc-TRODAT-1 brain SPECT.
AB  - Dopamine transporter (DAT) radiopharmaceuticals are capable of binding to the DAT
      with high selectivity, especially in the corpora striata, and have been widely
      used to evaluate parkinsonian disorder. However, only a few reports have
      mentioned about the extrastriatal pathologic DAT uptake. Herein we present an
      interesting case about the incidental discovery of pituitary macroadenoma with
      intense uptake of 99mTc-TRODAT-1.

PMID- 24445270
TI  - Avastin scintigraphy in surveillance of bevacizumab treatment in a patient with
      neurofibromatosis type 2: a case report.
AB  - A patient with neurofibromatosis type 2 (bilateral vestibular schwannomas) was
      treated with bevacizumab (anti-vascular endothelial growth factor [VEFG]
      monoclonal antibody). The left-sided tumor showed intense uptake on pretreatment
      In-bevacizumab scintigraphy, indicating VEGF production in the tumor, and no
      uptake 4 weeks later, demonstrating effective binding of nonradiolabeled
      bevacizumab to the VEGF produced in the tumor. The right-sided tumor showed no
      tracer uptake at any time point. Significant tumor volume reduction (assessed
      with MRI) and hearing improvement were observed on the left side. In-bevacizumab
      scintigraphy may be a promising upfront patient selection tool to identify
      patients who may benefit from expensive bevacizumab treatment. 

PMID- 24445271
TI  - Multifocal epithelioid hemangioendothelioma of the lower limbs detected by 18F
      FDG PET/MRI.
AB  - A 38-year-old man underwent surgical excision of a 1.5-cm subcutaneous nodule of
      the left leg. Histologic evaluation demonstrated the presence of an epithelioid
      hemangioendothelioma (EHE). The patient underwent 18F-FDG PET/MRI for staging.
      This examination demonstrated the presence of several soft tissue and bone
      lesions in the left lower limb without evidence of distant metastatic disease.
      The final diagnosis was multifocal EHE of the left lower limb. In this case, 18F
      FDG PET/MRI has been very useful in the correct staging of this rare presentation
      of EHE of the lower limbs.

PMID- 24445272
TI  - Invasive ductal carcinoma arising from dense accessory breast visualized with
      99mTc-MIBI breast-specific gamma imaging.
AB  - Primary accessory breast cancer is extremely rare, and the diagnostic efficacy of
      Tc-MIBI breast-specific gamma imaging (BSGI) has not been reported elsewhere. We
      present a case of primary carcinoma arising from dense accessory breast that was
      visualized with BSGI. A 43-year-old female patient with a palpable axillary mass
      underwent mammography, which showed dense parenchyma on both of the anatomic and
      accessory breasts with no abnormality. Subsequent BSGI showed no abnormal uptake
      in bilateral anatomic breasts, but focal abnormal uptake was noted in the
      accessory breast. Permanent pathologic evaluation confirmed invasive ductal
      carcinoma (not otherwise specified type) of the accessory breast. 

PMID- 24445273
TI  - 18F-FDG PET rarely provides additional information to 11C-methionine PET imaging
      in hyperparathyroidism.
AB  - AIM: The aim of this study was to assess the utility of combined C-methionine and
      F-FDG PET/CT imaging in hyperparathyroidism. PATIENTS AND METHODS: We reviewed
      all scans performed for hyperparathyroidism with both C-methionine and F-FDG
      PET/CT or PET in our institution since 1993. Forty-three patients (47 pairs of
      scans) were included (13 men and 30 women) with a mean age of 63 years. C
      methionine and F-FDG PET/CT scans were classified as positive or negative for
      localization of abnormal parathyroid tissue, and the site of uptake was noted in
      the positive scans. Other concurrent imaging (Tc-MIBI scintigraphy,
      ultrasonography, CT, or MRI) findings were also noted when performed. Clinical
      follow-up information was available in 27 patients (30 episodes). RESULTS: Of the
      47 PET scan episodes, 23 (49%) were positive. Twenty-two C-methionine scans
      showed abnormal focal localization of which 10 also showed concordant abnormal F
      FDG uptake. One patient was positive with F-FDG and negative with C-methionine.Of
      the 16 patients who underwent subsequent surgery, 6 had concordant C-methionine,
      F-FDG, and surgical findings; 6 had concordant C-methionine and surgical
      findings; 1 had concordant F-FDG and surgical findings; and 3 had both PET scans
      negative but had adenomas excised during surgery.Of the 3 with both PET scans
      negative and discordant surgical findings, 1 had mediastinal parathyroid
      lipoadenoma excised and 2 had normally sited parathyroid adenoma excised.
      CONCLUSIONS: F-FDG PET/CT rarely provides additional information and could be
      saved for patients in whom C-methionine PET/CT is negative.

PMID- 24445274
TI  - Pulmonary venous stenosis on ventilation-perfusion scintigraphy: a correlation
      with dynamic magnetic resonance pulmonary angiography.
AB  - A case of pulmonary vein stenosis as a result of prior atrial fibrillation focus
      procedures for atrial fibrillation, correlated with magnetic resonance (MR)
      pulmonary angiography, is presented. Restricted flow to the right lung in similar
      quantities measured by nuclear medicine and MR techniques is observed, with
      perfusion scintigraphy demonstrating decreased but not absent flow to the right
      lung and left lower lobe and with MRI demonstrating restriction of flow through
      the right and left lower pulmonary veins. The sharp differences in venous outflow
      can be seen by MR, whereas their effects are visible by scintigraphy. 

PMID- 24445275
TI  - MRI, enhanced CT, and FDG PET/CT in primary retroperitoneal mucinous
      cystadenocarcinoma.
AB  - Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare
      neoplasm. We present a case of PRMC with MRI, enhanced CT, and FDG PET/CT
      findings. Abdominal MRI showed a cystic lesion in the retroperitoneum with a
      mural nodule. The mural nodule showed progressive enhancement on enhanced CT and
      intense FDG uptake on early PET/CT with increased SUVmax on delayed PET/CT.
      Laparoscopy was performed. Retroperitoneal mucinous cystadenocarcinoma was
      confirmed histopathologically. Metastasis from gastrointestinal tract or ovary
      was excluded. This case indicates, although rare, PRMC should be considered when
      a hypermetabolic retroperitoneal cystic lesion with bilateral normal ovaries is
      found on FDG PET/CT. 

PMID- 24445276
TI  - 18F-FDG imaging of a rare cutaneous infection by Mycobacterium avium complex.
AB  - A 17-year-old male patient was admitted into our hospital with granulomatous
      eruption (primarily on the lower extremities), diarrhea, fever, and weight loss
      for 6 months. F-FDG PET/CT scan was performed to rule out the possibility of
      malignant metastasis or paraneoplastic syndromes. F-FDG PET/CT scan showed
      multiple bone and skin lesions with significantly intense FDG uptakes and lymph
      nodes with moderate FDG uptake. A biopsy of the skin lesions was performed, and
      the tissue was sent for a broad-range polymerase chain reaction amplification,
      which showed that the pathogenic organism was Mycobacterium avium complex. 

PMID- 24445277
TI  - FDG PET is a robust tool for the diagnosis of spondylodiscitis: a meta-analysis
      of diagnostic data.
AB  - PURPOSE: Spondylodiscitis is a rare infectious entity that requires multimodal
      diagnostic procedures. We evaluated the diagnostic performance of 18F-FDG PET on
      suspected spondylodiscitis based on published literature. PATIENTS AND METHODS:
      We searched the PubMed and EMBASE for pertinent studies up to July 2013. We
      implemented a patient-based meta-analysis of diagnostic data for FDG PET (the
      index test) against clinical, laboratory, and/or radiologic evidence of disease
      (the reference standard). A bivariate analysis was implemented to account for
      variability beyond the threshold effect. The individual patient data analysis was
      used to assess confounding factors that moderate diagnostic performance. RESULTS:
      Twelve studies provided the diagnostic data on FDG PET and spondylodiscitis,
      comprising 224 patients. The combined sensitivity across studies was 0.97 [95%
      confidence interval (CI), 0.83-1.00], the specificity was 0.88 (95% CI, 0.74
      0.95), and the area under the curve was 0.98 (95% CI, 0.96-0.99). For prior
      probabilities greater than 0.50, the corresponding positive predictive value was
      0.96 (0.93-0.98), and the negative predictive value was 0.85 (0.82-0.88). In the
      individual patient data analysis, metallic implants, dual PET/CT scanners and the
      addition of other imaging modalities to confirm disease were significant outcome
      moderators; only PET/CT remained significant in the adjusted analysis. PET/CT
      scanners improved the diagnostic performance, as opposed to the clinical data
      (age, sex, lesion site), which did not alter outcome. CONCLUSIONS: FDG PET is a
      robust diagnostic test when spondylodiscitis is suspected and is excellent for
      exclusion of infectious spondylodiscitis given its low likelihood ratio negative
      (<0.1). Importantly, this diagnostic test is unaffected by other confounders,
      including the presence of implants, when PET/CT is used.

PMID- 24445278
TI  - Effects of tadalafil once daily on maximum urinary flow rate in men with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia.
AB  - PURPOSE: Tadalafil significantly improves lower urinary tract symptoms suggestive
      of benign prostatic hyperplasia. We post hoc characterized changes in the maximum
      urinary flow rate using integrated data from 4 international, placebo controlled
      studies of tadalafil once daily for lower urinary tract symptoms suggestive of
      benign prostatic hyperplasia. MATERIALS AND METHODS: After a 4-week placebo lead
      in period 1,500 men were randomized to tadalafil 5 mg or placebo for 12 weeks.
      Data were analyzed using ANCOVA. Maximum urinary flow rate values were rank
      transformed for analysis. RESULTS: Baseline maximum urinary flow rate data were
      available on 1,371 men with a mean age of 63.1 years and end point data were
      available on 1,197. Tadalafil 5 mg significantly increased maximum urinary flow
      vs placebo (median 1.1 vs 0.4 ml per second, p = 0.003). At a baseline voided
      volume of 125 to less than 250 ml the median change in the maximum urinary flow
      rate was 0.9 and 1.2 ml per second (p = 0.142) in 731 patients, at a baseline of
      250 to 450 ml the change was -0.3 and 0.7 ml per second (p = 0.011) in 428, and
      at a baseline of greater than 450 ml the change was -0.2 and 2.0 ml per second (p
      = 0.186) in 38 for placebo and tadalafil, respectively. The difference was 0.3,
      1.0 and 2.2 ml per second, respectively. At a baseline maximum urinary flow rate
      of greater than 15 ml per second in 128 patients the median flow rate change was 
      2.1 and -0.8 ml per second (p = 0.246), at a maximum of 10 to 15 ml per second in
      522 the change was 0.2 and 0.8 ml per second (p = 0.044), and at a maximum of
      less than 10 ml per second in 547 the change was 1.2 and 1.8 ml per second (p =
      0.189) for placebo and tadalafil, respectively. Tadalafil improved I-PSS
      (International Prostate Symptom Score) voiding subscores significantly vs placebo
      across all baseline maximum urinary flow subgroups (each p <0.001). CONCLUSIONS:
      This integrated analysis revealed a small but statistically significant median
      maximum urinary flow rate improvement for tadalafil vs placebo. The numerical
      difference in the maximum urinary flow change from baseline between tadalafil and
      placebo increased with increased voided volume.

PMID- 24445280
TI  - Model for high-throughput screening of drug immunotoxicity--study of the anti
      microbial G1 over peritoneal macrophages using flow cytometry.
AB  - Quantitative Structure-Activity (mt-QSAR) techniques may become an important tool
      for prediction of cytotoxicity and High-throughput Screening (HTS) of drugs to
      rationalize drug discovery process. In this work, we train and validate by the
      first time mt-QSAR model using TOPS-MODE approach to calculate drug molecular
      descriptors and Linear Discriminant Analysis (LDA) function. This model correctly
      classifies 8258 out of 9000 (Accuracy = 91.76%) multiplexing assay endpoints of
      7903 drugs (including both train and validation series). Each endpoint correspond
      to one out of 1418 assays, 36 molecular and cellular targets, 46 standard type
      measures, in two possible organisms (human and mouse). After that, we determined
      experimentally, by the first time, the values of EC50 = 21.58 MUg/mL and
      Cytotoxicity = 23.6% for the anti-microbial/anti-parasite drug G1 over Balb/C
      mouse peritoneal macrophages using flow cytometry. In addition, the model
      predicts for G1 only 7 positive endpoints out 1251 cytotoxicity assays (0.56% of
      probability of cytotoxicity in multiple assays). The results obtained complement
      the toxicological studies of this important drug. This work adds a new tool to
      the existing pool of few methods useful for multi-target HTS of ChEMBL and other
      libraries of compounds towards drug discovery. 

PMID- 24445281
TI  - Paracrine effects of embryo-derived FGF4 and BMP4 during pig trophoblast
      elongation.
AB  - The crosstalk between the epiblast and the trophoblast is critical in supporting
      the early stages of conceptus development. FGF4 and BMP4 are inductive signals
      that participate in the communication between the epiblast and the extraembryonic
      ectoderm (ExE) of the developing mouse embryo. Importantly, however, it is
      unknown whether a similar crosstalk operates in species that lack a discernible
      ExE and develop a mammotypical embryonic disc (ED). Here we investigated the
      crosstalk between the epiblast and the trophectoderm (TE) during pig embryo
      elongation. FGF4 ligand and FGFR2 were detected primarily on the plasma membrane
      of TE cells of peri-elongation embryos. The binding of this growth factor to its
      receptor triggered a signal transduction response evidenced by an increase in
      phosphorylated MAPK/ERK. Particular enrichment was detected in the periphery of
      the ED in early ovoid embryos, indicating that active FGF signalling was
      operating during this stage. Gene expression analysis shows that CDX2 and ELF5,
      two genes expressed in the mouse ExE, are only co-expressed in the Rauber's
      layer, but not in the pig mural TE. Interestingly, these genes were detected in
      the nascent mesoderm of early gastrulating embryos. Analysis of BMP4 expression
      by in situ hybridisation shows that this growth factor is produced by nascent
      mesoderm cells. A functional test in differentiating epiblast shows that CDX2 and
      ELF5 are activated in response to BMP4. Furthermore, the effects of BMP4 were
      also demonstrated in the neighbouring TE cells, as demonstrated by an increase in
      phosphorylated SMAD1/5/8. These results show that BMP4 produced in the
      extraembryonic mesoderm is directly influencing the SMAD response in the TE of
      elongating embryos. These results demonstrate that paracrine signals from the
      embryo, represented by FGF4 and BMP4, induce a response in the TE prior to the
      extensive elongation. The study also confirms that expression of CDX2 and ELF5 is
      not conserved in the mural TE, indicating that although the signals that
      coordinate conceptus growth are similar between rodents and pigs, the gene
      regulatory network of the trophoblast lineage is not conserved in these species.

PMID- 24445279
TI  - A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits
      atherosclerotic plaque inflammation.
AB  - Inflammation is a key feature of atherosclerosis and a target for therapy.
      Statins have potent anti-inflammatory properties but these cannot be fully
      exploited with oral statin therapy due to low systemic bioavailability. Here we
      present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle
      carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate
      the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is
      mediated through the inhibition of the mevalonate pathway. We also apply statin
      rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of
      atherosclerosis and show that they accumulate in atherosclerotic lesions in which
      they directly affect plaque macrophages. Finally, we demonstrate that a 3-month
      low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression,
      while a 1-week high-dose regimen markedly decreases inflammation in advanced
      atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis
      nanotherapy that directly affects plaque inflammation. 

PMID- 24445282
TI  - Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity
      of gata1 and spi1 in primitive hematopoiesis.
AB  - Studies implicate a potential role for EAF1 in MLL-ELL induced leukemogenesis;
      however the biological function of EAF1 in this process remains unknown. In this
      study, we show that knockdown of zebrafish eaf1 by morpholinos caused serious
      defects in both primitive and definitive hematopoiesis. Using microarray
      analysis, we identified foxo3b as a target gene suppressed by eaf1. Ectopic
      expression of foxo3b in embryos mimicked the phenotypes exhibited in eaf1
      morphants, except that foxo3b had no effect on runx1 and c-myb expression while
      eaf1 morphants did not express these markers in the ventral wall of dorsal aorta.
      Subsequent experiments showed that a dominant negative form of Foxo3b (dn-foxo3b)
      partially restored primitive hematopoietic defects in eaf1 morphants, suggesting
      that foxo3b might serve as a key factor for mediating eaf1 function in primitive
      hematopoiesis. Furthermore, we observed that foxo3b inhibited the transcriptional
      activity of gata1 and spi1 through protein-protein interaction. Our findings not
      only suggest a function of eaf1 on hematopoiesis in vivo, but also reveal a novel
      regulatory pathway, eaf1-foxo3b-gata1/spi1, that may shed light on the role of
      EAF1 in MLL-ELL induced leukemogenesis.

PMID- 24445283
TI  - New triterpenoid saponins from the aerial parts of Schefflera kwangsiensis.
AB  - Eight new oleanane-type triterpenoid saponins, named schefflesides A-H (1-8),
      were isolated from the aerial parts of Schefflera kwangsiensis. The structures of
      these new compounds were established on the basis of hydrolysis and spectroscopic
      evidence, including 1D- and 2D-NMR (HSQC, HMBC, ROESY and TOCSY) and HR-MS
      analyses.

PMID- 24445284
TI  - Free energy landscape of G-protein coupled receptors, explored by accelerated
      molecular dynamics.
AB  - G-protein coupled receptors (GPCRs) mediate cellular responses to various
      hormones and neurotransmitters and are important targets for treating a wide
      spectrum of diseases. They are known to adopt multiple conformational states
      (e.g., inactive, intermediate and active) during their modulation of various cell
      signaling pathways. Here, the free energy landscape of GPCRs is explored using
      accelerated molecular dynamics (aMD) simulations as demonstrated on the M2
      muscarinic receptor, a key GPCR that regulates human heart rate and contractile
      forces of cardiomyocytes. Free energy profiles of important structural motifs
      that undergo conformational transitions upon GPCR activation and allosteric
      signaling are analyzed in detail, including the Arg(3.50)-Glu(6.30) ionic lock,
      the Trp(6.48) toggle switch and the hydrogen interactions between Tyr(5.58)
      Tyr(7.53). 

PMID- 24445285
TI  - A layer-nanostructured assembly of PbS quantum dot/multiwalled carbon nanotube
      for a high-performance photoswitch.
AB  - A layered nanostructure of a lead sulfide (PbS) quantum dot (QD)/multi-walled
      carbon nanotube (MWNT) hybrid was prepared by the electrostatic assembly after
      the phase transfer of PbS QDs from an organic to an aqueous phase. Well
      crystallized PbS QDs with a narrow diameter (5.5 nm) was mono-dispersed on the
      sidewalls of MWNT by the electrostatic adsorption. Near-infrared absorption of
      PbS/MWNT nanostructures was improved and controlled by the packing density of PbS
      QDs. Efficient charge transfer between PbS and MWNT at the interface resulted in
      a remarkable quenching of photoluminescence up to 28.6% and a blue-shift of
      emission band by 300 nm. This feature was facilitated by band energy levels based
      on the intimate contact through the electrostatic interaction. Two-terminal
      devices using PbS/MWNT nanostructures showed an excellent on/off switching
      photocurrent and good stability during 20 cycles under light illumination due to
      electron transfer from PbS to MWNT. The photoswitch exhibited a high photo
      sensitivity up to 31.3% with the photocurrent of 18.3 MUA under the light of 3.85
      mW/cm(2), which outperformed many QD/carbon-based nanocomposites. Results
      indicate that the electrostatic layered assembly of QD/MWNT nanostructure is an
      excellent platform for the fabrication of high-performance optoelectronic
      devices. 

PMID- 24445286
TI  - Integrating genomics into clinical oncology: ethical and social challenges from
      proponents of personalized medicine.
AB  - INTRODUCTION: The use of molecular tools to individualize health care, predict
      appropriate therapies, and prevent adverse health outcomes has gained significant
      traction in the field of oncology under the banner of "personalized medicine"
      (PM). Enthusiasm for PM in oncology has been fueled by success stories of
      targeted treatments for a variety of cancers based on their molecular profiles.
      Though these are clear indications of optimism for PM, little is known about the
      ethical and social implications of personalized approaches in clinical oncology.
      OBJECTIVE: The objective of this study is to assess how a range of stakeholders
      engaged in promoting, monitoring, and providing PM understand the challenges of
      integrating genomic testing and targeted therapies into clinical oncology.
      METHODS AND MATERIALS: The study involved the analysis of in-depth interviews
      with 117 stakeholders whose experiences and perspectives on PM span a wide
      variety of institutional and professional settings. RESULTS: Despite their
      considerable enthusiasm for this shift, promoters, monitors, and providers of PM
      identified 4 domains that provoke heightened ethical and social concerns: (1)
      informed consent for cancer genomic testing, (2) privacy, confidentiality, and
      disclosure of genomic test results, (3) access to genomic testing and targeted
      therapies in oncology, and (4) the costs of scaling up pharmacogenomic testing
      and targeted cancer therapies. CONCLUSIONS: These specific concerns are not
      unique to oncology, or even genomics. However, those most invested in the success
      of PM view oncologists' responses to these challenges as precedent setting
      because oncology is farther along the path of clinical integration of genomic
      technologies than other fields of medicine. This study illustrates that the rapid
      emergence of PM approaches in clinical oncology provides a crucial lens for
      identifying and managing potential frictions and pitfalls that emerge as health
      care paradigms shift in these directions.

PMID- 24445287
TI  - "Use it or lose it" as an alternative approach to protect genetic privacy in
      personalized medicine.

PMID- 24445288
TI  - Just caring: assessing the ethical and economic costs of personalized medicine.
AB  - Personalized medicine has been touted as a revolutionary form of cancer care. It
      has been portrayed as precision medicine, targeting with deadly accuracy cancer
      cells and sparing patients the debilitating broad-spectrum side effects of more
      traditional forms of cancer therapy. But personalized medicine still has its
      costs to patients and society, both moral and economic costs. How to recognize
      and address those issues will be the focus of this essay. We start with these
      questions: Does everyone faced with cancer have a moral right to the most
      effective cancer care available, no matter what the cost, no matter whether a
      particular individual has the personal ability to pay for that care or not? Or
      are there limits to the cancer care that anyone has a right to at social expense?
      If so, what are those limits and how are those limits to be determined? Are those
      limits a matter of both morality and economics? I will answer this last question
      in the affirmative. This is what I refer to as the "Just Caring" problem in
      health care. 

PMID- 24445289
TI  - Commentary on "initial management of prostate-specific antigen-detected, low-risk
      prostate cancer and the risk of death from prostate cancer." Aizer AA, Chen MH,
      Hattangadi J, D'Amico AV. Harvard Radiation Oncology program, Boston, MA.: BJU
      Int 2013. doi: 10.1111/j.1464-410X.2012.11789.x. [Epub ahead of print].
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The recently published
      Prostate Cancer Intervention versus Observation Trial (PIVOT) did not identify
      differences in prostate cancer-specific mortality or all-cause mortality among
      patients with low-risk disease managed conservatively vs those managed
      definitively; however, recently published data suggest that older men may harbour
      more aggressive disease than is identified at biopsy owing to sampling error and
      undergrading. Whether older men with apparent low-risk disease are placed at risk
      of prostate cancer-specific mortality when managed conservatively remains
      unknown. The study used population-level data to show that non-curative
      approaches for older men with low-risk prostate cancer do result in an increased
      risk of prostate cancer-specific mortality. Differences between our study and the
      PIVOT trial include the fact that we included a larger sample size, analysed the
      data using an 'as-treated' approach, and included a healthier cohort of men as
      evinced by lower 4-year all-cause mortality estimates in our study than in the
      PIVOT. Our results suggest that older men with apparent low-risk prostate cancer
      are at risk of undergrading, which probably explains the differences in prostate
      cancer-specific mortality observed between men managed conservatively vs those
      managed definitively. Our study suggests that alternative approaches to excluding
      occult, high grade prostate cancer are needed in such men. OBJECTIVE: To evaluate
      whether older age in men with low-risk prostate cancer increases the risk of
      prostate cancer-specific mortality (PCSM) when non-curative approaches are
      selected as initial management. PATIENTS AND METHODS: The study cohort consisted
      of 27 969 men, with a median age of 67 years, with prostate-specific antigen
      (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason
      score<=6, and PSA<=10) identified by the Surveillance, Epidemiology and End
      Results programme between 2004 and 2007. Fine and Gray's competing risk
      regression analysis was used to evaluate whether management with non-curative vs
      curative therapy was associated with an increased risk of PCSM after adjusting
      for PSA level, age at diagnosis and year of diagnosis. RESULTS: After a median
      follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer. Both
      older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02
      1.08; P<0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97-5.67; P<0.001)
      were significantly associated with an increased risk of PCSM. Men>the median age
      experienced increased estimates of PCSM when treated with non-curative as opposed
      to curative intent (P<0.001); this finding was not seen in men<=the median age (P
      = 0.17). CONCLUSION: Pending prospective validation, our study suggests that non
      curative approaches for older men with 'low-risk' prostate cancer result in an
      increased risk of PCSM, suggesting the need for alternative approaches to exclude
      occult, high grade prostate cancer in these men.

PMID- 24445290
TI  - Commentary on "secondary cancers after intensity-modulated radiotherapy,
      brachytherapy, and radical prostatectomy for the treatment of prostate cancer:
      incidence and cause-specific survival outcomes according to the initial treatment
      intervention." Zelefsky MJ, Pei X, Teslova T, Kuk D, Magsanoc JM, Kollmeier M,
      Cox B, Zhang Z. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer
      Center, New York, NY.: BJU Int 2012;110:1696-701. doi: 10.1111/j.1464
      410X.2012.11385.x. [Epub 2012 Aug 13].
AB  - Study Type-Therapy (case series) Level of Evidence 4 What's known on the subject?
      and What does the study add? Radiation Therapy for prostate cancer can increase
      the risk for the development of second cancers after treatment. This study
      highlights the fact that such second cancers within the pelvis do occur but are
      not as common as previously reported. In this report we also note that even among
      patients who develop second cancers, if detected earlier, the majority are alive
      5 years after the diagnosis. OBJECTIVE: To report on the incidence of secondary
      malignancy (SM) development after external-beam radiotherapy (EBRT) and
      brachytherapy (BT) for prostate cancer and to compare this with a cohort
      contemporaneously treated with radical prostatectomy (RP). MATERIALS AND METHODS:
      Between 1998 and 2001, 2658 patients with localized prostate cancer were treated
      with RP (n = 1348), EBRT (n = 897) or BT (n = 413). Using the RP cohort as a
      control we compared the incidence of SMs, such as rectal or bladder cancers noted
      within the pelvis, and the incidence of extrapelvic SMs. RESULTS: The 10-year SM
      free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%,
      respectively (RP vs EBRT, P = 0.002; RP vs BT, P = 0.37). The 10-year likelihoods
      for bladder or colorectal cancer SM development in the RP, BT and EBRT groups
      were 3%, 2% and 4%, respectively (P = 0.29). Multivariate analysis of predictors
      for development of all SMs showed that older age (P = 0.01) and history of
      smoking (P<0.001) were significant predictors for the development of a SM, while
      treatment intervention was not found to be a significant variable. Among 243
      patients who developed a SM, the 5-year likelihood of SM-related mortality among
      patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively,
      compared with 26.3% in the RP cohort; (P = 0.052). CONCLUSIONS: The incidence of
      SM after radiotherapy was not significantly different from that after RP when
      adjusted for patient age and smoking history. The incidence of bladder and rectal
      cancers was low for both EBRT- and BT-treated patients. Among patients who
      developed a SM, the likelihood of mortality related to the SM was not
      significantly different among the treatment cohorts.

PMID- 24445291
TI  - Commentary on "randomized clinical trial of vitamin D3 doses on prostatic vitamin
      D metabolite levels and Ki67 labeling in prostate cancer patients." Wagner D,
      Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo
      S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R, Department of Nutritional
      Sciences, University of Toronto, Ontario, Canada.: J Clin Endocrinol Metab
      2013;98(4):1498-507 [Epub 2013 Mar 5].
AB  - CONTEXT: Vitamin D3 might benefit prostate cancer (PCa) patients because prostate
      cells can locally synthesize the active hormone calcitriol. OBJECTIVE: Our
      objective was to determine the effects of oral vitamin D3 on vitamin D
      metabolites and PCa proliferative activity in prostate tissue. DESIGN AND
      SETTING: We conducted a double-blind randomized clinical trial at surgical
      oncology clinics in Toronto, Canada. PATIENTS: PCa patients (Gleason 6 or 7)
      participated in the study. Of 66 subjects who were enrolled, 63 completed the
      dosing protocol. INTERVENTION: Vitamin D3 (400, 10000, or 40000 IU/d) was orally
      administered before radical prostatectomy. MAIN OUTCOME MEASURES: We evaluated
      vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety
      measures, PTH, and prostate-specific antigen (PSA) were also assessed. RESULTS:
      Prostate tissue and serum levels of vitamin D metabolites, including calcitriol,
      increased dose dependently (P<.03) and were significantly higher in the 40000
      IU/d group than in every other dose group (P<.03). Prostate vitamin D metabolites
      correlated positively with serum levels (P<.0001). Ki67 measures did not differ
      significantly among vitamin D dose groups. However, cross-sectional analysis
      indicated that the calcitriol level attained in prostate was inversely associated
      with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign
      tissue (P<.05). Safety measures did not change adversely with dosing. Compared
      with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose
      groups at the end of the study (P< .02). CONCLUSIONS: Oral vitamin D3 raised
      prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and
      PTH. Although Ki67 expression did not differ among dose groups, its levels
      correlated inversely with prostate calcitriol. These suggestions of clinical
      benefit justify continued clinical research.

PMID- 24445292
TI  - Commentary on "the E3 ubiquitin ligase Siah2 contributes to castration-resistant
      prostate cancer by regulation of androgen receptor transcriptional activity." Qi
      J, Tripathi M, Mishra R, Sahgal N, Fazli L, Ettinger S, Placzek WJ, Claps G,
      Chung LW, Bowtell D, Gleave M, Bhowmick N, Ronai ZA, Signal Transduction Program,
      Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.:
      Cancer Cell 2013;23(6):332-46.
AB  - Understanding the mechanism underlying the regulation of the androgen receptor
      (AR), a central player in the development of castration-resistant prostate cancer
      (CRPC), holds promise for overcoming the challenge of treating CRPC. We
      demonstrate that the ubiquitin ligase Siah2 targets a select pool of NCOR1-bound,
      transcriptionally-inactive AR for ubiquitin-dependent degradation, thereby
      promoting expression of select AR target genes implicated in lipid metabolism,
      cell motility, and proliferation. Siah2 is required for prostate cancer cell
      growth under androgen-deprivation conditions in vitro and in vivo, and Siah2
      inhibition promotes prostate cancer regression upon castration. Notably, Siah2
      expression is markedly increased in human CRPCs. Collectively, we find that
      selective regulation of AR transcriptional activity by the ubiquitin ligase Siah2
      is important for CRPC development. 

PMID- 24445293
TI  - Commentary on "identification of 23 new prostate cancer susceptibility loci using
      the iCOGS custom genotyping array." Eeles RA, Olama AA, Benlloch S, Saunders EJ,
      Leongamornlert DA, Tymrakiewicz M, Ghoussaini M, Luccarini C, Dennis J,
      Jugurnauth-Little S, Dadaev T, Neal DE, Hamdy FC, Donovan JL, Muir K, Giles GG,
      Severi G, Wiklund F, Gronberg H, Haiman CA, Schumacher F, Henderson BE, Le
      Marchand L, Lindstrom S, Kraft P, Hunter DJ, Gapstur S, Chanock SJ, Berndt SI,
      Albanes D, Andriole G, Schleutker J, Weischer M, Canzian F, Riboli E, Key TJ,
      Travis RC, Campa D, Ingles SA, John EM, Hayes RB, Pharoah PD, Pashayan N, Khaw
      KT, Stanford JL, Ostrander EA, Signorello LB, Thibodeau SN, Schaid D, Maier C,
      Vogel W, Kibel AS, Cybulski C, Lubinski J, Cannon-Albright L, Brenner H, Park JY,
      Kaneva R, Batra J, Spurdle AB, Clements JA, Teixeira MR, Dicks E, Lee A, Dunning
      AM, Baynes C, Conroy D, Maranian MJ, Ahmed S, Govindasami K, Guy M, Wilkinson RA,
      Sawyer EJ, Morgan A, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van
      As NJ, Woodhouse CJ, Thompson A, Dudderidge T, Ogden C, Cooper CS, Lophatananon
      A, Cox A, Southey MC, Hopper JL, English DR, Aly M, Adolfsson J, Xu J, Zheng SL,
      Yeager M, Kaaks R, Diver WR, Gaudet MM, Stern MC, Corral R, Joshi AD, Shahabi A,
      Wahlfors T, Tammela TL, Auvinen A, Virtamo J, Klarskov P, Nordestgaard BG, Roder
      MA, Nielsen SF, Bojesen SE, Siddiq A, Fitzgerald LM, Kolb S, Kwon EM, Karyadi DM,
      Blot WJ, Zheng W, Cai Q, McDonnell SK, Rinckleb AE, Drake B, Colditz G,
      Wokolorczyk D, Stephenson RA, Teerlink C, Muller H, Rothenbacher D, Sellers TA,
      Lin HY, Slavov C, Mitev V, Lose F, Srinivasan S, Maia S, Paulo P, Lange E, Cooney
      KA, Antoniou AC, Vincent D, Bacot F, Tessier DC; COGS-Cancer Research UK GWAS
      ELLIPSE (part of GAME-ON) Initiative; Australian Prostate Cancer Bioresource; UK
      Genetic Prostate Cancer Study Collaborators/British Association of Urological
      Surgeons' Section of Oncology; UK ProtecT (Prostate testing for cancer and
      Treatment) Study
AB  - Prostate cancer is the most frequently diagnosed cancer in males in developed
      countries. To identify common prostate cancer susceptibility alleles, we
      genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from
      25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL
      Consortium. Twenty-three new prostate cancer susceptibility loci were identified
      at genome-wide significance (P<5*10(-8)). More than 70 prostate cancer
      susceptibility loci, explaining ~30% of the familial risk for this disease, have
      now been identified. On the basis of combined risks conferred by the new and
      previously known risk loci, the top 1% of the risk distribution has a 4.7-fold
      higher risk than the average of the population being profiled. These results will
      facilitate population risk stratification for clinical studies. 

PMID- 24445294
TI  - Commentary on "integrative genomic analyses reveal an androgen-driven somatic
      alteration landscape in early-onset prostate cancer." Weischenfeldt J, Simon R,
      Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz HJ, Stehr H,
      Rausch T, Jager N, Gu L, Bogatyrova O, Stutz AM, Claus R, Eils J, Eils R,
      Gerhauser C, Huang PH, Hutter B, Kabbe R, Lawerenz C, Radomski S, Bartholomae CC,
      Falth M, Gade S, Schmidt M, Amschler N, Habeta T, Galal R, Gjoni J, Kuner R, Baer
      C, Masser S, von Kalle C, Zichner T, Benes V, Raeder B, Mader M, Amstislavskiy V,
      Avci M, Lehrach H, Parkhomchuk D, Sultan M, Burkhardt L, Graefen M, Huland H,
      Kluth M, Krohn A, Sirma H, Stumm L, Steurer S, Grupp K, Sultmann H, Sauter G,
      Plass C, Brors B, Yaspo ML, Korbel JO, Schlomm T, Genome Biology Unit, European
      Molecular Biology Laboratory (EMBL), Heidelberg, Germany.: Cancer Cell
      2013;23(2):159-70.
AB  - Early-onset prostate cancer (EO-PCA) represents the earliest clinical
      manifestation of prostate cancer. To compare the genomic alteration landscapes of
      EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based
      genomics analyses in 11 tumors diagnosed at young age, and pursued comparative
      assessments with seven elderly-onset PCA genomes. Remarkable age-related
      differences in structural rearrangement (SR) formation became evident, suggesting
      distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of
      balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions
      including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen
      associated SRs. Data from a validation cohort of>10,000 patients showed age
      dependent androgen receptor levels and a prevalence of SRs affecting androgen
      regulated genes, further substantiating the activity of a characteristic
      "androgen-type" pathomechanism in EO-PCA. 

PMID- 24445295
TI  - Commentary on "age-related alterations in T-lymphocytes modulate key pathways in
      prostate tumorigenesis." De Angulo A, Faris R, Cavazos D, Jolly C, Daniel B,
      DeGraffenried L, Department of Nutritional Sciences, Dell Pediatric Research
      Institute, University of Texas, Austin, TX, USA.: Prostate 2013;73(8):855-64
      [Epub 2013 Mar 26].
AB  - BACKGROUND: The primary risk for prostate cancer is aging, often associated with
      inflammation. Evidence implicates progressive age-related immune dysfunction with
      increased prostate cancer incidence and mortality. The aged T-cell response is
      characterized by increased production of pro-inflammatory cytokines, which could
      significantly contribute to prostate tumorigenesis through induction of key
      inflammation-mediated pro-survival factors. METHODS: T-cell function of the young
      (<6 month-old) glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock-out mouse
      mimics many of the hallmarks observed in an aged (>22-month-old) mouse. Serum and
      splenic T-lymphocytes from young GPAT-1(-/-) (6 months) and aged wild type (22
      months) mice were collected for in vitro studies, including a cytokine
      immunoarray for serum cytokine levels, luciferase assays for NF-kappaB activation
      and Western blot analyses for protein expression. RESULTS: The T-cell cytokine
      profile of the GPAT-1(-/-) mice mirrored that observed in aged wild type mice,
      including higher expression levels of IL-17. Serum- and T-cell-derived factors
      induced NF-kappaB activity in normal, non-transformed and prostate cancer
      epithelial cells, correlating with re-localization of NF-kappaB and increased
      protein expression of downstream targets of NF-kappaB. CONCLUSION: The aging and
      aging-mimic mice produced circulating factors that induce pro-inflammatory
      pathways in prostate cells, most notably NF-kappaB. These findings provide
      evidence that an aged T-cell may directly contribute to the increased risk for
      prostate cancer in the elderly and establish that the GPAT-1(-/-) model, which
      mimics many of the characteristics of an aged immune system, is a viable tool for
      investigating this novel area of cancer risk.

PMID- 24445296
TI  - Commentary on "ETV1 directs androgen metabolism and confers aggressive prostate
      cancer in targeted mice and patients." Baena E, Shao Z, Linn DE, Glass K, Hamblen
      MJ, Fujiwara Y, Kim J, Nguyen M, Zhang X, Godinho FJ, Bronson RT, Mucci LA, Loda
      M, Yuan GC, Orkin SH, Li Z, Division of Hematology and Oncology, Boston
      Children's Hospital, Boston, MA, USA.: Genes Dev 2013;27(6):683-98.
AB  - Distinguishing aggressive from indolent disease and developing effective therapy
      for advanced disease are the major challenges in prostate cancer research.
      Chromosomal rearrangements involving ETS transcription factors, such as ERG and
      ETV1, occur frequently in prostate cancer. How they contribute to tumorigenesis
      and whether they play similar or distinct in vivo roles remain elusive. Here we
      show that in mice with ERG or ETV1 targeted to the endogenous Tmprss2 locus,
      either factor cooperated with loss of a single copy of Pten, leading to localized
      cancer, but only ETV1 appeared to support development of invasive adenocarcinoma
      under the background of full Pten loss. Mechanistic studies demonstrated that ERG
      and ETV1 control a common transcriptional network but largely in an opposing
      fashion. In particular, while ERG negatively regulates the androgen receptor (AR)
      transcriptional program, ETV1 cooperates with AR signaling by favoring activation
      of the AR transcriptional program. Furthermore, we found that ETV1 expression,
      but not that of ERG, promotes autonomous testosterone production. Last, we
      confirmed the association of an ETV1 expression signature with aggressive disease
      and poorer outcome in patient data. The distinct biology of ETV1-associated
      prostate cancer suggests that this disease class may require new therapies
      directed to underlying programs controlled by ETV1. 

PMID- 24445297
TI  - Commentary on "common genetic polymorphisms modify the effect of smoking on
      absolute risk of bladder cancer." Garcia-Closas M, Rothman N, Figueroa JD,
      Prokunina-Olsson L, Han SS, Baris D, Jacobs EJ, Malats N, De Vivo I, Albanes D,
      Purdue MP, Sharma S, Fu YP, Kogevinas M, Wang Z, Tang W, Tardon A, Serra C,
      Carrato A, Garcia-Closas R, Lloreta J, Johnson A, Schwenn M, Karagas MR, Schned
      A, Andriole G Jr., Grubb R 3rd, Black A, Gapstur SM, Thun M, Diver WR, Weinstein
      SJ, Virtamo J, Hunter DJ, Caporaso N, Landi MT, Hutchinson A, Burdett L, Jacobs
      KB, Yeager M, Fraumeni JF Jr., Chanock SJ, Silverman DT, Chatterjee N, Division
      of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD,
      USA.: Cancer Res 2013;73(7):2211-20 [Epub 2013 Mar 27].
AB  - Bladder cancer results from the combined effects of environmental and genetic
      factors, smoking being the strongest risk factor. Evaluating absolute risks
      resulting from the joint effects of smoking and genetic factors is critical to
      assess the public health relevance of genetic information. Analyses included up
      to 3,942 cases and 5,680 controls of European background in seven studies. We
      tested for multiplicative and additive interactions between smoking and 12
      susceptibility loci, individually and combined as a polygenic risk score (PRS).
      Thirty-year absolute risks and risk differences by levels of the PRS were
      estimated for U.S. males aged 50 years. Six of 12 variants showed significant
      additive gene-environment interactions, most notably NAT2 (P = 7*10(-4)) and
      UGT1A6 (P = 8*10(-4)). The 30-year absolute risk of bladder cancer in U.S. males
      was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers
      in the lowest quartile of the PRS to 9.9% for current smokers in the upper
      quartile. Risk difference estimates indicated that 8,200 cases would be prevented
      if elimination of smoking occurred in 100,000 men in the upper PRS quartile
      compared with 2,000 cases prevented by a similar effort in the lowest PRS
      quartile (P(additive) = 1*10(-4)). Thus, the potential impact of eliminating
      smoking on the number of bladder cancer cases prevented is larger for individuals
      at higher than lower genetic risk. Our findings could have implications for
      targeted prevention strategies. However, other smoking-related diseases, as well
      as practical and ethical considerations, need to be considered before any
      recommendations could be made.

PMID- 24445298
TI  - Commentary on "tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl)
      nitrosamine as the basis for urothelial cell carcinogenesis." He Z, Kosinska W,
      Zhao ZL, Wu XR, Guttenplan JB, Department of Basic Science, New York University
      Dental College, NY, USA.: Mutat Res 2012;742(1-2):92-5 [Epub 2011 Dec 4].
AB  - Bladder cancer is one of the few cancers that have been linked to carcinogens in
      the environment and tobacco smoke. Of the carcinogens tested in mouse chemical
      carcinogenesis models, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is one that
      reproducibly causes high-grade, invasive cancers in the urinary bladder, but not
      in any other tissues. However, the basis for such a high-level tissue-specificity
      has not been explored. Using mutagenesis in lacI (Big BlueTM) mice, we show here
      that BBN is a potent mutagen and it causes high-level of mutagenesis specifically
      in the epithelial cells (urothelial) of the urinary bladder. After a 2-6-week
      treatment of 0.05% BBN in the drinking water, mutagenesis in urothelial cells of
      male and female mice was about two orders of magnitude greater than the
      spontaneous mutation background. In contrast, mutagenesis in smooth muscle cells
      of the urinary bladder was about five times lower than in urothelial tissue. No
      appreciable increase in mutagenesis was observed in kidney, ureter, liver or
      forestomach. In lacI (Big BlueTM) rats, BBN mutagenesis was also elevated in
      urothelial cells, albeit not nearly as profoundly as in mice. This provides a
      potential explanation as to why rats are less prone than mice to the formation of
      aggressive form of bladder cancer induced by BBN. Our results suggest that the
      propensity to BBN-triggered mutagenesis of urothelial cells underlies its
      heightened susceptibility to this carcinogen and that mutagenesis induced by BBN
      represents a novel model for initiation of bladder carcinogenesis. 

PMID- 24445299
TI  - Commentary on "circulating angiostatin, bFGF, and Tie2/TEK levels and their
      prognostic impact in bladder cancer." Szarvas T, Jager T, Laszlo V, Kramer G,
      Klingler HC, vom Dorp F, Romics I, Ergun S, Rubben H, Department of Urology,
      University of Duisburg-Essen, Germany.: J Urol 2012;80(3):13-8 [Epub 2012 May
      17].
AB  - PURPOSE: A study was performed to assess the role and prognostic significance of
      angiostatin, basic fibroblast growth factor (bFGF), and tyrosine endothelial
      kinase (TEK/Tie2) in transitional cell bladder carcinoma. MATERIALS AND METHODS:
      Angiostatin, bFGF, and TEK serum concentrations were measured in 82 bladder
      cancer patients and 20 age-matched healthy controls using enzyme-linked
      immunosorbent assay. Results were compared with clinicopathologic and follow-up
      data with the Mann-Whitney U test and Kaplan-Meier, univariate and multivariate
      Cox regression analyses. RESULTS: We found significantly decreased angiostatin
      and TEK serum levels and mildly elevated bFGF concentrations in samples of
      bladder cancer patients compared with controls (P<.001, P<.001, and P = .083,
      respectively). Furthermore, high TEK serum levels were correlated with poor
      disease-specific and metastasis-free survival in muscle-invasive bladder cancer
      (P = .013, P = .018), whereas angiostatin and bFGF concentrations did not show
      any correlation with patients' prognosis. Multivariate analysis revealed high TEK
      levels (<1.60ng/mL) as borderline significant independent risk-factor of disease
      specific survival (HR 1.83, 95% CI 0.97-3.44, P = .061) and metastasis-free
      survival (HR 2.65, 95% CI 0.93-7.55, P = .069). CONCLUSION: The characteristic
      differences in the circulating levels of angiostatin, TEK, and bFGF between
      patients and controls, suggest the presence of a tumor-induced proangiogenic
      milieu in bladder cancer. Serum TEK levels may contribute to a more reliable
      preoperative risk stratification in muscle-invasive bladder cancer and therefore
      may help to optimize therapeutic decisions.

PMID- 24445301
TI  - Maternal sucrose-rich diet and fetal programming: changes in hepatic lipogenic
      and oxidative enzymes and glucose homeostasis in adult offspring.
AB  - Nutritional insults during pregnancy and lactation (P + L) are often associated
      with offspring health risks. We investigated the effect of maternal exposure to a
      sucrose-rich diet (SRD) during P + L on glucose and lipid metabolism of adult
      offspring regardless of post-weaning diet. Dams were fed an SRD or a control diet
      (CD) during P + L. After weaning, male offspring from SRD and CD dams were
      divided into two groups and fed a CD or SRD until 150 days old forming CD-CD, CD
      SRD, SRD-SRD and SRD-CD groups. Offspring where SRD was fed at any period of life
      showed: (1) increased adipose tissue weight without changes in the final body
      weight; (2) dyslipidemia as a result of increased very low density lipoprotein
      triglyceride secretion rate and decreased triglyceride clearance; (3) hepatic
      steatosis associated with increased activity of key enzymes involved in liver de
      novo lipogenesis and significant decrease of the activity of mitochondrial fatty
      acid oxidation enzyme. These results were more pronounced in CD-SRD and SRD-SRD
      groups. (4) Hyperglycemia without changes in insulin levels, plus a deterioration
      of intravenous glucose tolerance and intraperitoneal insulin tolerance test. We
      hypothesized that SRD during P + L could be associated with a programming effect
      on glucose homeostasis and hepatic lipid metabolism that predispose offspring to
      develop later-life insulin resistance and metabolic disorders, regardless of post
      natal diet. 

PMID- 24445300
TI  - Manipulation of monoubiquitin improves chilling tolerance in transgenic tobacco
      (Nicotiana tabacum).
AB  - Ubiquitin (Ub) is a multifunctional protein that mainly functions to tag proteins
      for selective degradation by the 26S proteasome. We cloned an Ub gene TaUb2 from
      wheat (Triticum aestivum L.) previously. To study the function of TaUB2 in
      chilling stress, sense and antisense Ub transgenic tobacco plants (Nicotiana
      tabacum L.), as well as wild type (WT) and vector control beta-glucuronidase (T
      GUS) plants, were used. Under stress, leaf wilting in sense plants was
      significantly less than in controls, but more severe in antisense plants.
      Meanwhile, the net photosynthetic rate (Pn) and the maximal photochemical
      efficiency of PSII (Fv/Fm) in sense plants were greater than controls, but lower
      in antisense plants during chilling stress and recovery. Less wilting in sense
      plants resulted from improved water status, which may be related to the
      accumulation of proline and solute sugar. Furthermore, as indicated by
      electrolyte leakage, membrane damage under stress was less in sense plants and
      more severe in antisense plants than controls. Consistent with electrolyte
      leakage, the malondialdehyde (MDA) content was less in sense plants, but more in
      antisense plants compared to controls. Meanwhile, the less accumulation of
      reactive oxygen species (ROS) and the greater antioxidant enzyme activity in
      sense plants implied the improved antioxidant competence by the overexpression of
      monoubiquitin gene Ta-Ub2 from wheat. We suggest that overexpressing Ub is a
      useful strategy to promote chilling tolerance. The improvement of ROS scavenging
      may be an important mechanism underlying the role of Ub in promoting plants
      tolerant to chilling stress. 

PMID- 24445302
TI  - Valacyclovir treatment of chronic fatigue in adolescents.
AB  - Chronic fatigue syndrome (CFS) presents with fatigue, low motivation, diminished
      mood, and reduced activity, all symptoms having extensive diagnostic overlaps
      with depression. Studies have linked chronic viral infections with CFS, and
      antiviral therapy has effectively treated CFS in adult patients. In a
      retrospective case series, 15 adolescents and preteens referred to the author for
      treatment-resistant depression or mood disorder were evaluated and found to have
      met the Fukuda diagnostic criteria for CFS. While a subset (4/15) had been
      diagnosed in the past with CFS, the majority had a current diagnosis of
      depression or a mood disorder. The Diagnostic and Statistical Manual-IV Text
      Revision (DSM-IV TR) criteria for depression were not met in all patients,
      although 3 cases of mood disorder not otherwise specified (MD-NOS) and 1 case of
      Tourette syndrome (TS) plus MD-NOS were diagnosed. Baseline scores on the
      Children's Depression Inventory (CDI) were below the cutoff for depression in all
      but 1 patient. Baseline self-assessment scales for CFS or fatigue were obtained
      and sleep was evaluated with sleep logs. All patients were treated subsequently
      with valacyclovir, with 93% having a positive response. At the end of treatment,
      scores on fatigue self-assessment scales improved significantly (P < .001). Vigor
      subscale scores also improved significantly (P < .001). Some patients experienced
      complete resolution of symptoms. Although not every patient was tested, available
      laboratory testing revealed increased counts of natural killer (NK) cells and
      decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who
      responded to valacyclovir. This article discusses the significance of infectious
      agents in the pathogenesis of psychiatric symptoms. The study's data support an
      intriguing hypothesis that a portion of treatment-resistant depression in fact
      may be undiagnosed CFS or other chronic viral infection. 

PMID- 24445303
TI  - Joel Robertson, PharmD: the critical role of the brain in health and how this
      leads medicine to one size fits one by Craig Gustafson.

PMID- 24445305
TI  - Haloperoxidase mediated quorum quenching by Nitzschia cf pellucida: study of the
      metabolization of N-acyl homoserine lactones by a benthic diatom.
AB  - Diatoms are known to produce a variety of halogenated compounds, which were
      recently shown to have a role in allelopathic interactions between competing
      species. The production of these compounds is linked to haloperoxidase activity.
      This research, has shown that this system may also be involved in diatom-bacteria
      interactions via the H2O2 dependent inactivation of a type of quorum sensing (QS)
      molecule, i.e., N-beta-ketoacylated homoserine lactones (AHLs), by a natural
      haloperoxidase system from the benthic diatom Nitzschia cf pellucida. The AHL
      degradation pathway towards corresponding halogenated derivatives was elucidated
      via HPLC-MS analysis and the synthesis of a broad series of novel halogenated AHL
      analogues as reference compounds. Furthermore, their biological activity as
      quorum sensing modulators was directly compared and evaluated against a series of
      naturally occurring beta-keto-AHLs. It has been demonstrated that the loss of the
      QS activity results from the final cleavage of the halogenated N-acyl chain of
      the signal molecules. 

PMID- 24445304
TI  - Thiopeptide antibiotics: retrospective and recent advances.
AB  - Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics
      that already counts with more than one hundred different entities. Although they
      are mainly isolated from soil bacteria, during the last decade, new members have
      been isolated from marine samples. Far from being limited to their innate
      antibacterial activity, thiopeptides have been found to possess a wide range of
      biological properties, including anticancer, antiplasmodial, immunosuppressive,
      etc. In spite of their ribosomal origin, these highly posttranslationally
      processed peptides have posed a fascinating synthetic challenge, prompting the
      development of various methodologies and strategies. Regardless of their limited
      solubility, intensive investigations are bringing thiopeptide derivatives closer
      to the clinic, where they are likely to show their veritable therapeutic
      potential. 

PMID- 24445306
TI  - Oxylipin diversity in the diatom family Leptocylindraceae reveals DHA derivatives
      in marine diatoms.
AB  - Marine planktonic organisms, such as diatoms, are prospective sources of novel
      bioactive metabolites. Oxygenated derivatives of fatty acids, generally referred
      to as oxylipins, in diatoms comprise a highly diverse and complex family of
      secondary metabolites. These molecules have recently been implicated in several
      biological processes including intra- and inter-cellular signaling as well as in
      defense against biotic stressors and grazers. Here, we analyze the production and
      diversity of C20 and C22 non-volatile oxylipins in five species of the family
      Leptocylindraceae, which constitute a basal clade in the diatom phylogeny. We
      report the presence of species-specific lipoxygenase activity and oxylipin
      patterns, providing the first demonstration of enzymatic production of
      docosahexaenoic acid derivatives in marine diatoms. The differences observed in
      lipoxygenase pathways among the species investigated broadly reflected the
      relationships observed with phylogenetic markers, thus providing functional
      support to the taxonomic diversity of the individual species. 

PMID- 24445307
TI  - Discovery of novel diterpenoids from Sinularia arborea.
AB  - Two novel diterpenoids, sinularbols A (1) and B (2), which were found to possess
      a new carbon skeleton were isolated from the soft coral Sinularia arborea. The
      structures of compounds 1 and 2 were elucidated by spectroscopic methods and 2
      displayed a moderately inhibitory effect on the generation of superoxide anion by
      human neutrophils. 

PMID- 24445309
TI  - Data for a common clinical dilemma.

PMID- 24445308
TI  - [Trauma bay haemoglobin level. Predictor of coagulation disorder in major
      trauma].
AB  - BACKGROUND: Trauma-induced coagulopathy is common in patients with major trauma
      and requires early and appropriate treatment for bleeding control. Even in
      emergency laboratory, the availability of standard coagulation tests is
      associated with certain latencies and devices for viscoelastic haemostasis
      diagnosis (thromboelastometry) are not routinely established in major trauma
      centres. PURPOSE: We searched for a laboratory parameter with fast availability
      by point of care blood gas analysis and reliable correlation with coagulation
      parameters. METHODS: We analyzed the trauma patients of a single level one trauma
      centre from 2005-2011 and particularly evaluated the correlation between
      haemoglobin (Hb) and coagulation parameters and the correlation of Hb and
      parameters indicating tissue perfusion. All patients who were directly admitted
      from the scene of an accident to the trauma centre had an injury severity score
      (ISS) > 9, had a complete revised injury severity classification (RISC) and blood
      samples that were taken in the emergency department (ED) immediately after
      admission were included. Correlations were tested using the Pearson test (r) with
      a two-tailed significance level of p < 0.05. RESULTS: A total of 425 patients met
      inclusion criteria presenting with a mean age of 43 years, 76% male gender and
      mean ISS of 30.4. Significant correlation (p < 0.01) between Hb and prothrombin
      time (Quick) (r = 0.652), Hb and partial thromboplastin time (PTT) (r = - 0.434),
      Hb and platelet count (r = 0.501) and Hb and base excess (BE) (0.408) was found.
      No significant correlation between Hb and lactate was found. CONCLUSION: We found
      a robust correlation of Hb and Quick in a single centre trauma population. These
      data suggest that especially severely injured trauma patients with persistent
      bleeding might benefit from an Hb-based algorithm for early correction of
      coagulation disorders. Further studies with larger trauma populations are
      required to confirm our findings.

PMID- 24445310
TI  - Design, synthesis, biological evaluation, and comparative docking study of 1,2,4
      triazolones as CB1 receptor selective antagonists.
AB  - Cannabinoids are potentially useful for the treatment of several diseases. In the
      present work, we report the syntheses and biological evaluations of 1,2,4
      triazolone derivatives designed using a combined approach of scaffold hopping and
      pharmacophore-oriented method. These compounds exhibited interesting antagonistic
      activity to the cannabinoid CB1 receptor. The preliminary structure-activity
      relationships were further discussed. In addition, docking simulations were
      performed on the good bioactive compound 5c and the low potent compound 5d,
      respectively, on the basis of homology models of the CB1 and CB2 receptors, which
      were constructed based on human beta2-adrenoreceptor and optimized in a membrane
      environment by MD simulations. Calculation of the binding modes gave us insights
      into the structural requirements for improving the cannabinoid receptor
      bioactivity and selectivity. 

PMID- 24445311
TI  - Benzofuran derivatives as a novel class of inhibitors of mTOR signaling.
AB  - High-throughput screening (HTS) hit 1 was previously identified as an inhibitor
      of the Akt/mTOR (Akt/mammalian target of rapamycin) signaling, which is a major
      target in oncology. The cytotoxicity of 1 was determined on a panel of human
      cancer cells lines with an IC50 comprised between 30 and 140 MUM. Subsequent
      structure--activity relationship (SAR) studies led us to the identification of
      compounds that displayed an enhanced cytotoxicity. We demonstrated also that
      these molecules directly bind to mTOR complex 1 (mTORC1) and inhibit its kinase
      activity.

PMID- 24445312
TI  - Novel spirooxindole-pyrrolidine compounds: synthesis, anticancer and molecular
      docking studies.
AB  - Novel spirooxindole-pyrrolidine compounds have been synthesised through 1,3
      dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or
      thioproline with the dipolarophile 3-(1H-imidazol-2-yl)-2-(1H-indole-3
      carbonyl)acrylonitrile under the optimised reaction condition. Synthesised
      compounds were evaluated for their anticancer activity against A549 human lung
      adenocarcinoma cancer cell line. Among the 29 tested compounds 4j, 6b and 6h
      showed very high activity 66.3%, 64.8% and 66.3% at 25 MUg/mL concentration
      against A549 lung adenocarcinoma cancer cell line. These spirooxindole
      pyrrolidine compounds can be promising therapeutic agents for A549 lung
      adenocarcinoma cancer cell line.

PMID- 24445313
TI  - Novel bronchodilatory quinazolines and quinoxalines: synthesis and biological
      evaluation.
AB  - A series of heterocyclic derivatives analogous to (-)vasicinone, in which the
      vasicinone C-ring was replaced with alkyl chain terminated by tertiary amine was
      prepared. N3, C4-O, C4-S or C4-N were used as the sites of attachment. The 4-[3
      (1-piperidyl)propylsulfanyl]derivatives displayed bronchodilatory effect at low
      micromolar concentrations on isolated rat trachea, and low toxicity both on
      Balb/c 3T3 mouse fibroblast cells and in mice. 

PMID- 24445314
TI  - Acute pancreatitis decreases the sensitivity of pancreas-projecting dorsal motor
      nucleus of the vagus neurones to group II metabotropic glutamate receptor
      agonists in rats.
AB  - Recent studies have shown that pancreatic exocrine secretions (PES) are modulated
      by dorsal motor nucleus of the vagus (DMV) neurones, whose activity is finely
      tuned by GABAergic and glutamatergic synaptic inputs. Group II metabotropic
      glutamate receptors (mGluR) decrease synaptic transmission to pancreas-projecting
      DMV neurones and increase PES. In the present study, we used a combination of in
      vivo and in vitro approaches aimed at characterising the effects of caerulein
      induced acute pancreatitis (AP) on the vagal neurocircuitry modulating pancreatic
      functions. In control rats, microinjection of bicuculline into the DMV increased
      PES, whereas microinjections of kynurenic acid had no effect. Conversely, in AP
      rats, microinjection of bicuculline had no effect, whereas kynurenic acid
      decreased PES. DMV microinjections of the group II mGluR agonist APDC and whole
      cell recordings of excitatory currents in identified pancreas-projecting DMV
      neurones showed a reduced functional response in AP rats compared to controls.
      Moreover, these changes persisted up to 3 weeks following the induction of AP.
      These data demonstrate that AP increases the excitatory input to pancreas
      projecting DMV neurones by decreasing the response of excitatory synaptic
      terminals to group II mGluR agonist. 

PMID- 24445315
TI  - Shank2 mutant mice display a hypersecretory response to cholera toxin.
AB  - Shank2 is a PDZ (PSD-95/discs large/ZO-1)-based adaptor that has been suggested
      to regulate membrane transporting proteins in the brain and epithelial tissues.
      Here, we report that Shank2 mutant (Shank2(-/-)) mice exhibit aberrant fluid and
      ion transport in the intestine. Molecular characterization using epithelial
      tissues from Shank2(+/+) and Shank2(-/-) mice revealed that a long spliceoform of
      Shank2 (Shank2E) is predominantly expressed in the pancreatic, renal and
      intestinal epithelia. In functional assays, deletion of Shank2 increased the
      cystic fibrosis transmembrane conductance regulator (CFTR)-dependent short
      circuit currents by 84% (P < 0.05) and 101% (P < 0.05) in the mouse colon and
      rectum, respectively. Disruption of the CFTR-Shank2-phosphodiesterase 4D protein
      complex appeared to be mostly responsible for the changes in CFTR activities.
      Notably, Shank2 deletion profoundly increased cholera toxin-induced fluid
      accumulation in the mouse intestine (~90%, P < 0.01). Analyses with chemical
      inhibitors confirmed that the hyperactivation of CFTR channel function is
      responsible for the increased response to cholera toxin. These results suggest
      that Shank2 is a key molecule that participates in epithelial homeostasis, in
      particular to prevent overt secretory responses caused by epithelial pathogens.

PMID- 24445316
TI  - Purinergic signalling contributes to chemoreception in the retrotrapezoid nucleus
      but not the nucleus of the solitary tract or medullary raphe.
AB  - Several brain regions are thought to function as important sites of
      chemoreception including the nucleus of the solitary tract (NTS), medullary raphe
      and retrotrapezoid nucleus (RTN). In the RTN, mechanisms of chemoreception
      involve direct H(+)-mediated activation of chemosensitive neurons and indirect
      modulation of chemosensitive neurons by purinergic signalling. Evidence suggests
      that RTN astrocytes are the source of CO2-evoked ATP release. However, it is not
      clear whether purinergic signalling also influences CO2/H(+) responsiveness of
      other putative chemoreceptors. The goals of this study are to determine if
      CO2/H(+)-sensitive neurons in the NTS and medullary raphe respond to ATP, and
      whether purinergic signalling in these regions influences CO2 responsiveness in
      vitro and in vivo. In brain slices, cell-attached recordings of membrane
      potential show that CO2/H(+)-sensitive NTS neurons are activated by focal ATP
      application; however, purinergic P2-receptor blockade did not affect their
      CO2/H(+) responsiveness. CO2/H(+)-sensitive raphe neurons were unaffected by ATP
      or P2-receptor blockade. In vivo, ATP injection into the NTS increased
      cardiorespiratory activity; however, injection of a P2-receptor blocker into this
      region had no effect on baseline breathing or CO2/H(+) responsiveness. Injections
      of ATP or a P2-receptor blocker into the medullary raphe had no effect on
      cardiorespiratory activity or the chemoreflex. As a positive control we confirmed
      that ATP injection into the RTN increased breathing and blood pressure by a P2
      receptor-dependent mechanism. These results suggest that purinergic signalling is
      a unique feature of RTN chemoreception. 

PMID- 24445317
TI  - Deficiency of slow skeletal muscle troponin T causes atrophy of type I slow
      fibres and decreases tolerance to fatigue.
AB  - The total loss of slow skeletal muscle troponin T (ssTnT encoded by TNNT1 gene)
      due to a nonsense mutation in codon Glu(180) causes a lethal form of recessively
      inherited nemaline myopathy (Amish nemaline myopathy, ANM). To investigate the
      pathogenesis and muscle pathophysiology of ANM, we studied the phenotypes of
      partial and total loss of ssTnT in Tnnt1 gene targeted mice. An insertion of
      neomycin resistance cassette in intron 10 of Tnnt1 gene caused an approximately
      60% decrease in ssTnT protein expression whereas cre-loxP-mediated deletion of
      exons 11-13 resulted in total loss of ssTnT, as seen in ANM muscles. In diaphragm
      and soleus muscles of the knockdown and knockout mouse models, we demonstrated
      that ssTnT deficiency resulted in significantly decreased levels of other slow
      fibre-specific myofilament proteins whereas fast fibre-specific myofilament
      proteins were increased correspondingly. Immunohistochemical studies revealed
      that ssTnT deficiency produced significantly smaller type I slow fibres and
      compensatory growth of type II fast fibres. Along with the slow fibre atrophy and
      the changes in myofilament protein isoform contents, ssTnT deficiency
      significantly reduced the tolerance to fatigue in soleus muscle. ssTnT-deficient
      soleus muscle also contains significant numbers of small-sized central nuclei
      type I fibres, indicating active regeneration. The data provide strong support
      for the essential role of ssTnT in skeletal muscle function and the causal effect
      of its loss in the pathology of ANM. This observation further supports the
      hypothesis that the function of slow fibres can be restored in ANM patients if a
      therapeutic supplement of ssTnT is achieved. 

PMID- 24445318
TI  - Muscle contraction increases interstitial nitric oxide as predicted by a new
      model of local blood flow regulation.
AB  - The prevailing metabolic theory of local blood flow regulation suggests the
      dilatation of arterioles in response to tissue hypoxia via the emission of
      multiple metabolic vasodilators by parenchymal cells. We have proposed a
      mechanism of regulation, built from well-known components, which assumes that
      arterioles are normally dilated in metabolically active tissues, due to the
      emission of NO by the endothelium of microvessels. Regulation of local blood flow
      aims at preventing an excessive supply of oxygen (O2) and glucose to the tissue
      and thus provides an adequate supply, in contrast to the metabolic regulation
      theory which requires permanent hypoxia to generate the metabolic vasodilators.
      The mediator of the restrictive signal is superoxide anion (O2(-)) released by
      membrane NAD(P)H oxidases into the interstitial space, where it neutralizes NO at
      a diffusion-limited rate. This model predicts that the onset of muscle
      contraction will lead to the cessation of O2(-) production, which will cause an
      elevation of interstitial NO concentration and an increase in fluorescence of the
      NO probe DAF-FM after its conversion to DAF-T. The time course of DAF-T
      fluorescence in contracting muscle is predicted by also considering the washout
      from the muscle of the interstitially loaded NO indicator. Experiments using
      pulse fluorimetry confirmed an increase in the interstitial concentration of NO
      available for reaction with DAF-FM during bouts of muscle contraction. The sharp
      increase in interstitial [NO] is consistent with the hypothesis that the
      termination of the neutralizing superoxide flow into the interstitium is
      associated with the activation of mitochondria and a reduction of the
      interstitial oxygen tension. The advantage of the new model is its ability to
      explain the interaction of metabolic activity and local blood flow through the
      adequate delivery of glucose and oxygen. 

PMID- 24445319
TI  - Adult spinal motoneurones are not hyperexcitable in a mouse model of inherited
      amyotrophic lateral sclerosis.
AB  - In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is
      progressive degeneration of motoneurones, it has been suggested that an intrinsic
      hyperexcitability of motoneurones (i.e. an increase in their firing rates),
      contributes to excitotoxicity and to disease onset. Here we show that there is no
      such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried
      out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1
      around the time of the first muscle fibre denervations. We showed that the
      recruitment current, the voltage threshold for spiking and the frequency
      intensity gain in the primary range are all unchanged in most spinal
      motoneurones, despite an increased input conductance. On its own, increased input
      conductance would decrease excitability, but the homeostasis for excitability is
      maintained due to an upregulation of a depolarizing current that is activated
      just below the spiking threshold. However, this homeostasis failed in a
      substantial fraction of motoneurones, which became hypoexcitable and unable to
      produce sustained firing in response to ramps of current. We found similar
      results both in lumbar motoneurones recorded in anaesthetized mice, and in
      sacrocaudal motoneurones recorded in vitro, indicating that the lack of
      hyperexcitability is not caused by anaesthetics. Our results suggest that, if
      excitotoxicity is indeed a mechanism leading to degeneration in ALS, it is not
      caused by the intrinsic electrical properties of motoneurones but by extrinsic
      factors such as excessive synaptic excitation. 

PMID- 24445320
TI  - Vasoactive agonists exert dynamic and coordinated effects on vascular smooth
      muscle cell elasticity, cytoskeletal remodelling and adhesion.
AB  - In this study, we examined the ability of vasoactive agonists to induce dynamic
      changes in vascular smooth muscle cell (VSMC) elasticity and adhesion, and tested
      the hypothesis that these events are coordinated with rapid remodelling of the
      cortical cytoskeleton. Real-time measurement of cell elasticity was performed
      with atomic force microscopy (AFM) and adhesion was assessed with AFM probes
      coated with fibronectin (FN). Temporal data were analysed using an Eigen
      decomposition method. Elasticity in VSMCs displayed temporal oscillations with
      three components at approximately 0.001, 0.004 and 0.07 Hz, respectively.
      Similarly, adhesion displayed a similar oscillatory pattern. Angiotensin II (ANG
      II, 10(-6) M) increased (+100%) the amplitude of the oscillations, whereas the
      vasodilator adenosine (ADO, 10(-4) M) reduced oscillation amplitude (-30%). To
      test whether the oscillatory changes were related to the architectural
      alterations in cortical cytoskeleton, the topography of the submembranous actin
      cytoskeleton (100-300 nm depth) was acquired with AFM. These data were analysed
      to compare cortical actin fibre distribution and orientation before and after
      treatment with vasoactive agonists. The results showed that ANG II increased the
      density of stress fibres by 23%, while ADO decreased the density of the stress
      fibres by 45%. AFM data were supported by Western blot and confocal microscopy.
      Collectively, these observations indicate that VSMC cytoskeletal structure and
      adhesion to the extracellular matrix are dynamically altered in response to
      agonist stimulation. Thus, vasoactive agonists probably invoke unique mechanisms
      that dynamically alter the behaviour and structure of both the VSMC cytoskeleton
      and focal adhesions to efficiently support the normal contractile behaviour of
      VSMCs.

PMID- 24445321
TI  - Genetic ablation of ryanodine receptor 2 phosphorylation at Ser-2808 aggravates
      Ca(2+)-dependent cardiomyopathy by exacerbating diastolic Ca2+ release.
AB  - Phosphorylation of the cardiac ryanodine receptor (RyR2) by protein kinase A
      (PKA) at Ser-2808 is suggested to mediate the physiological 'fight or flight'
      response and contribute to heart failure by rendering the sarcoplasmic reticulum
      (SR) leaky for Ca(2+). In the present study, we examined the potential role of
      RyR2 phosphorylation at Ser-2808 in the progression of Ca(2+)-dependent
      cardiomyopathy (CCM) by using mice genetically modified to feature elevated SR
      Ca(2+) leak while expressing RyR2s that cannot be phosphorylated at this site
      (S2808A). Surprisingly, rather than alleviating the disease phenotype,
      constitutive dephosphorylation of Ser-2808 aggravated CCM as manifested by
      shortened survival, deteriorated in vivo cardiac function, exacerbated SR Ca(2+)
      leak and mitochondrial injury. Notably, the deteriorations of cardiac function,
      myocyte Ca(2+) handling, and mitochondria integrity were consistently worse in
      mice with heterozygous ablation of Ser-2808 than in mice with complete ablation.
      Wild-type (WT) and CCM myocytes expressing unmutated RyR2s exhibited a high level
      of baseline phosphorylation at Ser-2808. Exposure of these CCM cells to protein
      phosphatase 1 caused a transitory increase in Ca(2+) leak attributable to partial
      dephosphorylation of RyR2 tetramers at Ser-2808 from more fully phosphorylated
      state. Thus, exacerbated Ca(2+) leak through partially dephosphorylated RyR2s
      accounts for the prevalence of the disease phenotype in the heterozygous S2808A
      CCM mice. These results do not support the importance of RyR2
      hyperphosphorylation in Ca(2+)-dependent heart disease, and rather suggest roles
      for the opposite process, the RyR2 dephosphorylation at this residue in
      physiological and pathophysiological Ca(2+) signalling. 

PMID- 24445322
TI  - Hypermuscular mice with mutation in the myostatin gene display altered calcium
      signalling.
AB  - Myostatin, a member of the transforming growth factor beta family, is a potent
      negative regulator of skeletal muscle growth, as myostatin-deficient mice show a
      great increase in muscle mass. Yet the physical performance of these animals is
      reduced. As an explanation for this, alterations in the steps in excitation
      contraction coupling were hypothesized and tested for in mice with the 12 bp
      deletion in the propeptide region of the myostatin precursor (Mstn(Cmpt-dl1Abc)
      or Cmpt). In voluntary wheel running, control C57BL/6 mice performed better than
      the mutant animals in both maximal speed and total distance covered. Despite the
      previously described lower specific force of Cmpt animals, the pCa-force
      relationship, determined on chemically permeabilized fibre segments, did not show
      any significant difference between the two mouse strains. While resting
      intracellular Ca(2+) concentration ([Ca(2+)]i) measured on single intact flexor
      digitorum brevis (FDB) muscle fibres using Fura-2 AM was similar to control (72.0
      +/- 1.7 vs. 78.1 +/- 2.9 nM, n = 38 and 45), the amplitude of KCl-evoked calcium
      transients was smaller (360 +/- 49 vs. 222 +/- 45 nM, n = 22) in the mutant
      strain. Similar results were obtained using tetanic stimulation and Rhod-2 AM,
      which gave calcium transients that were smaller (2.42 +/- 0.11 vs. 2.06 +/- 0.10
      DeltaF/F0, n = 14 and 13, respectively) on Cmpt mice. Sarcoplasmic reticulum (SR)
      calcium release flux calculated from these transients showed a reduced peak (23.7
      +/- 3.0 vs. 15.8 +/- 2.1 mM s(-1)) and steady level (5.7 +/- 0.7 vs. 3.7 +/- 0.5
      mM s(-1)) with no change in the peak-to-steady ratio. The amplitude and spatial
      spread of calcium release events detected on permeabilized FDB fibres were also
      significantly smaller in mutant mice. These results suggest that reduced SR
      calcium release underlies the reduced muscle force in Cmpt animals.

PMID- 24445324
TI  - Self-assembled tunable networks of sticky colloidal particles.
AB  - Surfaces decorated with dense arrays of microscopic fibres exhibit unique
      materials properties, including superhydrophobicity and low friction. Nature
      relies on 'hairy' surfaces to protect blood capillaries from wear and infection
      (endothelial glycocalyx). Here we report on the discovery of self-assembled
      tunable networks of microscopic polymer fibres ranging from wavy colloidal 'fur'
      to highly interconnected networks. The networks emerge via dynamic self-assembly
      in an alternating electric field from a non-aqueous suspension of 'sticky'
      polymeric colloidal particles with a controlled degree of polymerization. The
      resulting architectures are tuned by the frequency and amplitude of the electric
      field and surface properties of the particles. We demonstrate, using atomic layer
      deposition, that the networks can serve as a template for a transparent
      conductor. These self-assembled tunable materials are promising candidates for
      large surface area electrodes in batteries and organic photovoltaic cells, as
      well as for microfluidic sensors and filters. 

PMID- 24445323
TI  - Autotransporters but not pAA are critical for rabbit colonization by Shiga toxin
      producing Escherichia coli O104:H4.
AB  - The outbreak of diarrhoea and haemolytic uraemic syndrome that occurred in
      Germany in 2011 was caused by a Shiga toxin-producing enteroaggregative
      Escherichia coli (EAEC) strain. The strain was classified as EAEC owing to the
      presence of a plasmid (pAA) that mediates a characteristic pattern of aggregative
      adherence on cultured cells, the defining feature of EAEC that has classically
      been associated with virulence. Here we describe an infant rabbit-based model of
      intestinal colonization and diarrhoea caused by the outbreak strain, which we use
      to decipher the factors that mediate the pathogen's virulence. Shiga toxin is the
      key factor required for diarrhoea. Unexpectedly, we observe that pAA is
      dispensable for intestinal colonization and development of intestinal pathology.
      Instead, chromosome-encoded autotransporters are critical for robust colonization
      and diarrhoeal disease in this model. Our findings suggest that conventional
      wisdom linking aggregative adherence to EAEC intestinal colonization is false for
      at least a subset of strains. 

PMID- 24445325
TI  - Cervical osteoid osteoma progression to osteoblastoma.

PMID- 24445326
TI  - Traumatic atlantoaxial dislocation with type II odontoid fracture.

PMID- 24445327
TI  - Holospinal epidural abscess complicated with bilateral psoas muscle abscess.

PMID- 24445328
TI  - Short bowel syndrome and small bowel transplantation.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update of recent
      advances in the areas of short bowel syndrome (SBS) and small bowel
      transplantation (SBT). RECENT FINDINGS: Recent reports from two of the largest
      multicenter randomized, controlled trials in patients with SBS support the safety
      and efficacy of teduglutide as an aid to parenteral nutrition weaning. In well
      selected SBS patients, outcomes as diverse as survival, macronutrient absorption
      and parenteral nutrition weaning are improved after autologous gastrointestinal
      reconstructive surgery. SBT is no longer considered investigational and given
      improved outcomes noted in recent reports, indications for transplantation are
      expanding. Although SBT early survival rates are approaching those of other organ
      allografts, long-term graft survival remains suboptimal. SUMMARY: Recently
      available trophic factors hold promise as aids in restoring freedom from
      parenteral nutrition support; however, their long-term benefits, preferred timing
      of administration in relation to the onset of SBS, optimal patient selection for
      use, duration of treatment and cost effectiveness require further study. Despite
      recent evidence of improved early survival after SBT, more dedicated research is
      needed to design more effective strategies to better tolerize small bowel grafts,
      prevent rejection and, ultimately, improve long-term outcomes. Reserved for well
      selected patients, autologous gastrointestinal reconstruction should be
      considered complementary and not antagonistic to SBT.

PMID- 24445329
TI  - Proteases and small intestinal barrier function in health and disease.
AB  - PURPOSE OF REVIEW: To summarize the recent knowledge regarding intestinal
      proteases and the gut barrier. RECENT FINDINGS: It is now well established that
      intestinal proteases, such as matrix metalloproteinase (MMP)-1, MMP-3, MMP-10 and
      MMP-12, are key players in the development of ulcers in inflammatory bowel
      disease, have direct effects on epithelial barrier function and are involved in
      epithelial restitution. However, more recent work has suggested that the membrane
      anchored epithelial cell serine protease matriptase is critical in maintaining
      the gut barrier, and roles have also been described for elastase, MMP-13,
      gelatinases, mast cell proteases and proteases derived from parasites and gut
      bacteria. Interestingly, epithelial proteases often co-localize with epithelial
      adherens junctions, and nonepithelial-derived proteases have junctional proteins
      as targets. SUMMARY: The role of proteases in controlling normal barrier function
      in the gut is now becoming very clear, to go alongside their role in intestinal
      inflammation.

PMID- 24445330
TI  - The sustained trajectory of small bowel research.

PMID- 24445331
TI  - Towards the determination of the nutritional needs of the body and its microbiome
      in sickness and in health.

PMID- 24445332
TI  - Spatial demonstratives and perceptual space: describing and remembering object
      location.
AB  - Spatial demonstratives - terms including this and that - are among the most
      common words across all languages. Yet, there are considerable differences
      between languages in how demonstratives carve up space and the object
      characteristics they can refer to, challenging the idea that the mapping between
      spatial demonstratives and the vision and action systems is universal. In seven
      experiments we show direct parallels between spatial demonstrative usage in
      English and (non-linguistic) memory for object location, indicating close
      connections between the language of space and non-linguistic spatial
      representation. Spatial demonstrative choice in English and immediate memory for
      object location are affected by a range of parameters - distance, ownership,
      visibility and familiarity - that are lexicalized in the demonstrative systems of
      some other languages. The results support a common set of constraints on language
      used to talk about space and on (non-linguistic) spatial representation itself.
      Differences in demonstrative systems across languages may emerge from basic
      distinctions in the representation and memory for object location. In turn, these
      distinctions offer a building block from which non-spatial uses of demonstratives
      can develop. 

PMID- 24445333
TI  - Antibiofilm and antimicrobial efficacy of DispersinB(r)-KSL-W peptide-based wound
      gel against chronic wound infection associated bacteria.
AB  - The medical importance of bacterial biofilms has increased with the recognition
      of biofilms as one of the major contributors to the slow or non-healing chronic
      wounds such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers.
      Being a protected community of microorganisms, biofilms are notoriously
      refractory to antibiotic treatments. As the conventional treatment modalities
      have proven ineffective, this study provides the in vitro evidence to support the
      use of a novel combination of DispersinB((r)) antibiofilm enzyme that inhibits
      biofilm formation and disperses preformed biofilm, and thus making the biofilm
      bacteria more susceptible to a broad-spectrum KSL-W antimicrobial peptide. The
      combination of DispersinB((r)) and KSL-W peptide showed synergistic antibiofilm
      and antimicrobial activity against chronic wound infection associated biofilm
      embedded bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA),
      Staphylococcus epidermidis, Coagulase-negative Staphylococci (CoNS), and
      Acinetobacter baumannii. In addition, the wound gel formulation comprising
      DispersinB((r)), KSL-W peptide, and a gelling agent Pluronic F-127 showed a broad
      spectrum and enduring antimicrobial activity against test organisms. Furthermore,
      as compared to commercial wound gel Silver-SeptTM, DispersinB((r))-KSL-W peptide
      based wound gel was significantly more effective in inhibiting the biofilm
      embedded MRSA, S. epidermidis, CoNS, Vancomycin-resistant Enterococci, A.
      baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa (P < 0.05). Thus,
      this study provides promising evidence for the potential application of
      antibiofilm-antimicrobial DispersinB((r))-KSL-W wound gel in chronic wound
      management.

PMID- 24445334
TI  - Localization of polysaccharides in isolated and intact cuticles of eucalypt,
      poplar and pear leaves by enzyme-gold labelling.
AB  - The presence and characteristics of cuticle polysaccharides have been
      demonstrated by staining and spectroscopic methods, but their location in the
      cuticle remains unclear. Furthermore, according to the prevailing model,
      polysaccharides are believed to be restricted to the cuticular layer and absent
      in the cuticle proper. With the aim of gaining insight into cuticular ultra
      structure focussing on polysaccharides, cellulose and pectins have been
      identified and located in the transversal sections of isolated and intact adaxial
      leaf cuticles of Eucalyptus globulus, Populus * canescens and Pyrus communis by
      means of enzyme gold-labelling (Au-cellulase, EC 3.2.1.4, and -pectinase, EC
      3.2.1.15) and transmission electron microscopy (TEM). The structure of the
      interface between the cuticle and the cell wall underneath was observed to
      influence the process of enzymatic isolation of leaf cuticles. Cellulose and
      pectins were detected for the first time in enzymatically isolated cuticles,
      sometimes appearing closely underneath the epicuticular wax layer. The location
      and presence of polysaccharides in intact and isolated leaf cuticles may have
      multiple implications, such as when estimating the bi-directional transport of
      substances between plant organs and the surrounding environment, or when
      interpreting organ ontogeny. The results are discussed within a plant ontological
      and ecophysiological context.

PMID- 24445336
TI  - Assessment of different carbohydrates as exogenous carbon source in cultivation
      of cyanobacteria.
AB  - Glucose is the substrate most widely used as exogenous carbon source for
      heterotrophic cultivation of cyanobacteria. Due to limited information about the
      use of different carbohydrates as carbon sources to support cyanobacterial
      heterotrophic metabolism, the objective of this work was to evaluate different
      monosaccharides (arabinose, fructose, galactose, glucose, mannose and xylose),
      disaccharides (lactose, maltose, sucrose and trehalose) and polysaccharides
      (carboxymethylcellulose, cassava starch, Hi-maize((r)), maltodextrin Corn Globe
      1805((r)) and xylan) as exogenous carbon source for heterotrophic culture of
      cyanobacterium Phormidium sp. The batch cultivation using fructose as organic
      carbon source resulted in the highest (p < 0.05) cell biomass (5,540 mg/L) in
      parallel with the highest (p < 0.05) substrate yield coefficient (0.67
      mg(biomass)/mg(fructose)). Mannose was the carbon source with the highest (p <
      0.05) substrate consumption rate (3,185.7 mg/L/day) and maltodextrin was the
      carbohydrate with major potential to produce biomass (1,072.8 mg(biomass)/L/day)
      and lipids (160.8 mg(lipids)/L/day). Qualitatively, the fatty acid profiles of
      the lipid extract from Phormidium sp. showed predominance of saturated chains for
      the cultures grown with most of the carbon sources, with the exception of the
      ones grown with xylose and maltodextrin.

PMID- 24445335
TI  - Atomic structure of luminescent centers in high-efficiency Ce-doped w-AlN single
      crystal.
AB  - Rare-earth doped wurtzite-type aluminum nitride (w-AlN) has great potential for
      high-efficiency electroluminescent applications over a wide wavelength range.
      However, because of their large atomic size, it has been difficult to stably dope
      individual rare-earth atoms into the w-AlN host lattice. Here we use a reactive
      flux method under high pressure and high temperature to obtain cerium (Ce) doped
      w-AlN single crystals with pink-colored luminescence. In order to elucidate the
      atomic structure of the luminescent centers, we directly observe individual Ce
      dopants in w-AlN using annular dark-field scanning transmission electron
      microscopy. We find that Ce is incorporated as single, isolated atoms inside the
      w-AlN lattice occupying Al substitutional sites. This new synthesis method
      represents a new alternative strategy for doping size-mismatched functional atoms
      into wide band-gap materials. 

PMID- 24445337
TI  - Effects of ultrasonic and microwave pretreatments on lipid extraction of
      microalgae.
AB  - The extraction of lipids from microalgal cells using ultrasonic and microwave
      pretreatments is mechanistically evaluated based on the distribution of cell
      fragments, the lipid content analysis, the scanning electron microscopic (SEM)
      observation of ruptured microalgal cells, and the analysis of fatty acids. The
      results indicate that microwave pretreatment extracts lipids more rapidly and
      efficiently as compared to ultrasonic pretreatment. The rupture of cells in the
      microwave process is due to the tremendous pressure caused by the rapid heating
      of the moisture inside the microalgal cells, whereas in the ultrasonic process
      the microalgal cells are ruptured by shock waves from cavitation bubbles outside
      the cells. The fatty acid composition of the respective lipids extracted via the
      two types of pretreatment did not vary significantly from one another. These
      results demonstrate that the microwave process is rapid and more effective than
      the ultrasonic process for lipid extraction from microalgae. 

PMID- 24445339
TI  - Concerted halogen bonding and orthogonal metal-halogen interactions in dimers of
      lithium formamidinate and halogenated formamidines: an ab initio study.
AB  - Dimers of lithium formamidinate, CH(NH)2Li, and halogenated formamidines,
      HN=CHNHX, (X=Cl, Br, or I) are used as model systems to investigate simultaneous
      N-X...N and N-Li...N interactions, in tandem with orthogonal Li...X interactions.
      Geometry optimizations and energy calculations for the dimers are examined with
      the MP2 method and the M06-2X hybrid functional and the aug-cc-pVTZ basis set
      (the aug-cc-pVTZ-PP basis set is used for the iodine atom). Both methods predict
      the formation of a planar structure of C2v symmetry, regardless of the identity
      of the halogen atom. In this structure, the identities of the constituent
      monomers are essentially lost. Accordingly, the N-X...N interactions emerge as a
      rather symmetric quasi-linear N...X...N, where the covalent N-X bond in the
      halogenated formamidine is replaced by a partly covalent N...X interaction.
      Formation of the C2v structure is also driven by a fairly linear N...Li...N
      interaction parallel to the N...X...N interaction, and a Li...X interaction
      orthogonal to both the N...X...N and N...Li...N interactions. The strength of the
      interactions increases with the size of the halogen. The robustness of the
      interactions suggests that the dimers studied here or suitable analogues may find
      diverse applications including their use as novel polymeric synthons. 

PMID- 24445340
TI  - Invasive fungal infections in the ICU: how to approach, how to treat.
AB  - Invasive fungal infections are a growing problem in critically ill patients and
      are associated with increased morbidity and mortality. Most of them are due to
      Candida species, especially Candida albicans. Invasive candidiasis includes
      candidaemia, disseminated candidiasis with deep organ involvement and chronic
      disseminated candidiasis. During the last decades rare pathogenic fungi, such as
      Aspergillus species, Zygomycetes, Fusarium species and Scedosporium have also
      emerged. Timely diagnosis and proper treatment are of paramount importance for a
      favorable outcome. Besides blood cultures, several laboratory tests have been
      developed in the hope of facilitating an earlier detection of infection. The
      antifungal armamentarium has also been expanded allowing a treatment choice
      tailored to individual patients' needs. The physician can choose among the old
      class of polyenes, the older and newer azoles and the echinocandins. Factors
      related to patient's clinical situation and present co-morbidities, local
      epidemiology data and purpose of treatment (prophylactic, pre-emptive, empiric or
      definitive) should be taken into account for the appropriate choice of antifungal
      agent. 

PMID- 24445338
TI  - Prevalence and incidence of HIV infection, trends, and risk factors among persons
      aged 15-64 years in Kenya: results from a nationally representative study.
AB  - BACKGROUND: Enhanced HIV surveillance using demographic, behavioral, and biologic
      data from national surveys can provide information to evaluate and respond to HIV
      epidemics efficiently. METHODS: From October 2012 to February 2013, we conducted
      a 2-stage cluster sampling survey of persons aged 18 months to 64 years in 9
      geographic regions in Kenya. Participants answered questionnaires and provided
      blood for HIV testing. We estimated HIV prevalence, HIV incidence, described
      trends in HIV prevalence over the past 5 years, and identified factors associated
      with HIV infection. This analysis was restricted to persons aged 15-64 years.
      RESULTS: HIV prevalence was 5.6% [95% confidence interval (CI): 4.9 to 6.3] in
      2012, a significant decrease from 2007, when HIV prevalence, excluding the North
      Eastern region, was 7.2% (95% CI: 6.6 to 7.9). HIV incidence was 0.5% (95% CI:
      0.2 to 0.9) in 2012. Among women, factors associated with undiagnosed HIV
      infection included being aged 35-39 years, divorced or separated, from urban
      residences and Nyanza region, self-perceiving a moderate risk of HIV infection,
      condom use with the last partner in the previous 12 months, and reporting 4 or
      more lifetime number of partners. Among men, widowhood, condom use with the last
      partner in the previous 12 months, and lack of circumcision were associated with
      undiagnosed HIV infection. CONCLUSIONS: HIV prevalence has declined in Kenya
      since 2007. With improved access to treatment, HIV prevalence has become more
      challenging to interpret without data on new infections and mortality. Correlates
      of undiagnosed HIV infection provide important information on where to prioritize
      prevention interventions to reduce transmission of HIV in the broader population.

PMID- 24445341
TI  - Gold nanoparticles decorated with mannose-6-phosphate analogues.
AB  - Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate
      analogues is described by: (a) synthesis of a cyclic sulfate precursor to access
      the carbohydrate head-group by nucleophilic displacement with an appropriate
      nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via
      Huisgen's cycloaddition, the Julia reaction, or the thiol-ene reaction under
      ultrasound activation. With the resulting compounds in hand, gold nanoparticles
      could be functionalized with various carbohydrate derivatives (glycoconjugates)
      and then tested for angiogenic activity. It was observed that the length and
      flexibility of the spacer separating the sugar analogue from the nanoparticle
      have little influence on the biological response. One particular nanoparticle
      system substantially inhibits blood vessel growth in contrast to activation by
      the corresponding monomeric glycoconjugate, thereby demonstrating the importance
      of multivalency in angiogenic activity. 

PMID- 24445342
TI  - A greener, efficient approach to Michael addition of barbituric acid to
      nitroalkene in aqueous diethylamine medium.
AB  - An efficient method for the synthesis of a variety of pyrimidine derivatives 3a-t
      by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2a-k as
      Michael acceptor using an aqueous medium and diethylamine is described. This 1,4
      addition strategy offers several advantages, such as using an economic and
      environmentally benign reaction media, high yields, versatility, and shorter
      reaction times. The synthesized compounds were identified by 1H-NMR, 13C-NMR,
      CHN, IR, and MS. The structure of compound 3a was further confirmed by single
      crystal X-ray structure determination. 

PMID- 24445343
TI  - Design and synthesis of some new 1,3,4-thiadiazines with coumarin moieties and
      their antioxidative and antifungal activity.
AB  - A series of newly disubstituted (compounds 4a,b) and trisubstituted 1,3,4
      thiadiazines 5a-l with various substituents was prepared utilizing different
      thiosemicarbazides and 3-alpha-bromoacetylcoumarins as starting compounds. The
      structures of the synthesized 1,3,4-thiadiazines are elucidated and confirmed
      utilizing the corresponding analytical and spectroscopic data. All of the new
      thiadiazine derivatives were tested for their antioxidant activity, employing
      different antioxidant assays (DPPH scavenging activity, iron chelating activity,
      power reducing activity). Compounds 5b, 5f, 5j and 4b were proven to be the best
      DPPH radical scavengers, while compounds 5h and 5j have shown the best iron
      chelating activity. Thiadiazine derivatives were also tested on their antifungal
      activity against four mycotoxicogenic fungi, Aspergillus flavus, A. ochraceus,
      Fusarium graminearum and F. verticillioides. The best antifungal against A.
      flavus was proven to be compound 5e, while compounds 4a and 5c were the best
      antifungals on A. ochraceus, and compound 5g showed the best antifungal activity
      on F. verticillioides. 

PMID- 24445344
TI  - A new sesquilignan glucoside from Uraria sinensis.
AB  - A new sesquilignan glucoside, urariasinoside A (1), together with eight known
      compounds, including two lignans, a sesquilignan, a dilignan, and four flavonoid
      derivatives were isolated from the aerial parts of Uraria sinensis. Their
      structures were determined on the basis of extensive spectroscopic analyses and
      comparison with literature data. Compound 1 was evaluated for in vitro
      cytotoxicity activity against HL-60, SMMC-7721, A549, MCF-7, SW480, and BEAS-2B
      cell lines. 

PMID- 24445345
TI  - Validation of a liquid chromatography-electrospray ionization-tandem mass
      spectrometry method for determination of all-trans retinoic acid in human plasma
      and its application to a bioequivalence study.
AB  - A sensitive, reliable and specific LC-MS-MS method was developed and validated
      for the identification and quantitation of all-trans retinoic acid (ATRA) in
      human plasma. Acitretin was used as the internal standard (IS). After liquid
      liquid extraction of 500 MUL plasma with methyl tert-butyl ether (MTBE), ATRA and
      the IS were chromatographed on a HyPURITY C18 column (150 mm*2.1 mm, 5 MUm) with
      the column temperature set at 40  degrees C. The mobile phase was consisted of
      40% phase A (MTBE-methanol-acetic acid, 50:50:0.5, v/v) and 60% phase B (water
      methanol-acetic acid, 50:50:0.5, v/v) with a flow rate of 0.3 mL/min. The API
      4000 triple quadrupole mass spectrometer was operated in multiple reaction
      monitoring (MRM) mode via the positive electrospray ionization interface using
      the transition m/z 301.4->123.1 for ATRA and m/z 326.9->177.1 for IS,
      respectively. The calibration curve was linear over the range of 0.45-217.00
      ng/mL (r>=0.999) with a lower limit of quantitation (LLOQ) of 0.45 ng/mL. The
      intra- and inter-day precisions values were below 8% relative standard deviation
      and the accuracy was from 98.98% to 106.19% in terms of relative error. The
      validated method was successfully applied in a bioequivalence study of ATRA in
      Chinese healthy volunteers.

PMID- 24445346
TI  - Comment on "Volume shrinkage of a metal-organic framework host induced by the
      dispersive attraction of guest gas molecules".

PMID- 24445348
TI  - Retrospective observational study on the incidence of incisional hernias after
      colorectal carcinoma resection with follow-up CT scan.
AB  - BACKGROUND: Incisional hernia (IH) is the most frequent complication after
      colorectal carcinoma (CRC) resection. The incidence depends on the method of
      follow-up, where ultrasound yields a significant number of additional hernias
      compared to clinical examination alone. Not many studies have evaluated the value
      of computed tomography (CT) to diagnose IH. METHODS: The CorreCT study is a
      retrospective cohort study of IH after CRC surgery by clinical examination and by
      CT, as reported in the medical files. Additional independent reviewing of all CTs
      by two radiologists was performed. RESULTS: From the oncological database (2004
      2008) of the hospital, 598 patients with CRC were identified. The data of 448
      consecutive patients who underwent surgery were analyzed. Tumors were resected by
      laparotomy in 366 patients (81.7 %), by laparoscopy in 76 patients (17.0 %) and
      by laparotomy after conversion in 6 patients (1.3 %). A clinical follow-up by the
      surgeon in 282 patients (62.9 %) with a mean duration of 33 months, yielded 49
      patients with IH (17.4 %). The mean time of IH diagnosis (T1) was 19 months. Only
      16 patients (33 %) underwent a hernia repair. For 363 patients (81.0 %), CT
      follow-up was available for a mean period of 30 months. In 84 patients (23.1 %),
      an IH was diagnosed with a mean T1 of 21 months. The review of all CTs by two
      independent radiologists yielded additional IH in 19 and 21 patients,
      respectively, increasing the IH rate to 29.1 and 29.7 %, respectively, and with a
      decrease in mean T1 to 14 months. The inter-observer agreement between the
      radiologists had a Kappa-statistic of 0.73 (95 % CI 0.65-0.81). For those
      patients with disagreement between the radiologists, a final agreement was made
      during an additional reviewing session of both radiologists, increasing the IH
      rate to 35.0 %. Comparing clinical follow-up, routine CT follow-up, and
      reassessed CT follow-up we found a statistically significant difference between
      the three methods of IH detection (p < 0.0001). CONCLUSION: CT follow-up can
      identify significantly more IH than clinical examination alone, in particular if
      the radiologist focuses on IH development. Furthermore, we showed that focused CT
      evaluation diagnosed IH 7 months earlier than routine CT and 5 months earlier
      than clinical follow-up alone.

PMID- 24445347
TI  - Non-invasive mapping of deep-tissue lymph nodes in live animals using a
      multimodal PET/MRI nanoparticle.
AB  - The invasion status of tumour-draining lymph nodes (LNs) is a critical indicator
      of cancer stage and is important for treatment planning. Clinicians currently use
      planar scintigraphy and single-photon emission computed tomography (SPECT) with
      (99m)Tc-radiocolloid to guide biopsy and resection of LNs. However, emerging
      multimodality approaches such as positron emission tomography combined with
      magnetic resonance imaging (PET/MRI) detect sites of disease with higher
      sensitivity and accuracy. Here we present a multimodal nanoparticle, (89)Zr
      ferumoxytol, for the enhanced detection of LNs with PET/MRI. For genuine
      translational potential, we leverage a clinical iron oxide formulation, altered
      with minimal modification for radiolabelling. Axillary drainage in naive mice and
      from healthy and tumour-bearing prostates was investigated. We demonstrate that
      (89)Zr-ferumoxytol can be used for high-resolution tomographic studies of
      lymphatic drainage in preclinical disease models. This nanoparticle platform has
      significant translational potential to improve preoperative planning for nodal
      resection and tumour staging. 

PMID- 24445349
TI  - Homoepitaxial tunnel barriers with functionalized graphene-on-graphene for charge
      and spin transport.
AB  - The coupled imperatives for reduced heat dissipation and power consumption in
      high-density electronics have rekindled interest in devices based on tunnelling.
      Such devices require mating dissimilar materials, raising issues of
      heteroepitaxy, layer uniformity, interface stability and electronic states that
      severely complicate fabrication and compromise performance. Two-dimensional
      materials such as graphene obviate these issues and offer a new paradigm for
      tunnel barriers. Here we demonstrate a homoepitaxial tunnel barrier structure in
      which graphene serves as both the tunnel barrier and the high-mobility transport
      channel. We fluorinate the top layer of a graphene bilayer to decouple it from
      the bottom layer, so that it serves as a single-monolayer tunnel barrier for both
      charge and spin injection into the lower graphene channel. We demonstrate high
      spin injection efficiency with a tunnelling spin polarization >60%, lateral
      transport of spin currents in non-local spin-valve structures and determine spin
      lifetimes with the Hanle effect. 

PMID- 24445350
TI  - Epigenetic modulators mitigate angiogenesis through a complex transcriptomic
      network.
AB  - In this review, we summarize the knowledge pertaining to the role of epigenetics
      in the regulation of angiogenesis. In particular, we show that lysine acetylation
      and cytosine methylation are important transcriptional regulators of angiogenic
      genes in endothelial cells. Lysine acetylation and cytosine methylation
      inhibitors idiosyncratically tune the transcriptome and affect expression of key
      modulators of angiogenesis such as VEGF and eNOS. Transcriptomic profiling also
      reveals a series of novel genes that are concomitantly affected by epigenetic
      modulators. The reversibility and overall tolerability of currently available
      epigenetic inhibitors open up the prospect of therapeutic intervention in
      pathologies where angiogenesis is exacerbated. This type of multitargeted
      strategy has the major advantage of overcoming the compensatory feedback
      mechanisms that characterize single anti-angiogenic factors. 

PMID- 24445351
TI  - Pharmaceutical drugs-the good and the not so good: together, we can make it
      better.

PMID- 24445352
TI  - Attitudes toward and use of complementary and alternative medicine among Hispanic
      and white mothers.
AB  - CONTEXT: Complementary and alternative medicine (CAM) use has become more
      prevalent in the United States. Little is known, however, regarding the ethnic
      and language differences of mothers as related to their beliefs about and use of
      CAM. OBJECTIVE: This study intended to examine the differences in CAM beliefs and
      use in English- and Spanish-speaking Hispanic and white mothers of children
      undergoing surgery. DESIGN: The research team employed a cross-sectional survey
      design. SETTING: Mothers were recruited from the Children's Hospital of Orange
      County (CHOC) in Southern California, and they completed the study's surveys on
      the day of their children's outpatient surgery. PARTICIPANTS: A total of 206
      mothers participated: (1) 42 English-speaking, non-Hispanic white (ESW) women;
      (2) 92 English-speaking Hispanic (ESH) women; and (3) 72 Spanish-speaking
      Hispanic (SSH) women. OUTCOME MEASURES: Participants completed (1) the Holistic
      and Complementary and Alternative Medicine Questionnaire (HCAMQ), which captured
      beliefs about holistic health measures and about the validity of CAM; and (2) a
      checklist identifying past and present use of 27 different CAM therapies.
      RESULTS: The research team analyzed and controlled for demographic differences
      using linear regression, and the analysis revealed significant group differences
      in CAM use (P < .0001). ESW mothers and ESH mothers used more CAM than SSH
      mothers (P = .02). No significant differences were observed between groups for
      CAM related beliefs. CONCLUSIONS: After controlling for socioeconomic status, the
      research team found that SSH mothers used less CAM compared to ESH and ESW
      mothers. Employment of culturally specific measures of CAM use may be necessary
      to understand fully the differences in CAM use between Spanish- and English
      speaking mothers as well as to understand the medical conditions that prompt CAM
      use.

PMID- 24445353
TI  - Effectiveness of biofield therapy for individuals with sickle cell disease in
      Africa.
AB  - CONTEXT: Individuals with sickle cell disease (SCD) in Africa have to manage most
      of their painful episodes at home, mainly due to insufficient medical services.
      In the past, the research team had observed that some individuals with SCD had
      experienced symptomatic improvement after administration of biofield therapy.
      OBJECTIVE: The research team intended to evaluate the influence of repeated
      administration of biofield therapy on clinical outcomes for individuals with SCD
      in Africa. DESIGN: The research team designed a prospective, open label,
      nonrandomized, case-control study. SETTING: This study was performed at Le Centre
      de Medecine Mixte d'Anemie SS (CMMASS) in Kinshasa, Democratic Republic of Congo
      (DRC). PARTICIPANTS: Participants were individuals with SCD who received
      treatments at CMMASS. INTERVENTION: Twenty participants aged 3-36 y underwent
      Okada purifying therapy (OPT), a form of biofield therapy, every weekday for 1 y
      (OPT group). OPT was administered by certified practitioners approved by the MOA
      International Corporation. The research team also constructed an age- and gender
      matched control group (n = 20) from regular patients at the clinic. OUTCOME
      MEASURES: Participants in both groups received blood tests at baseline, after 6
      mo, and at end of the 1-y intervention period. A follow-up survey was also
      conducted 33 mo after the 1-y administration of OPT. RESULTS: The OPT group
      showed a significant improvement in its blood data, including hemoglobin, total
      bilirubin, alanine aminotransferase (ALT), creatinine, and white blood cell (WBC)
      count (P < .001). The control group had less improvement in hemoglobin (P < .001)
      and total bilirubin (P < .001) than the OPT group. Its creatinine level increased
      significantly (P < .001), and ALT and WBC count remained at the same level after
      1 y. For the OPT group, SCD-related episodes, such as painful crises, blood
      transfusions, and hospitalizations, decreased more significantly than for the
      control group (P < .001). The follow-up survey revealed that those who continued
      using OPT regularly had remained in better condition for approximately 3 y after
      the intervention period than those who did not (P = .0014). CONCLUSION: Repeated
      administration of biofield therapy is considered effective for individuals with
      SCD who have various symptoms, although the care given by the practitioners may
      have had some influence on the clinical outcomes.

PMID- 24445354
TI  - Chronic fatigue syndrome: a personalized integrative medicine approach.
AB  - Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a relatively
      common illness, yet despite considerable investigation, current treatments have
      modest benefits, and the prognosis remains poor. Because CFS/ME is a
      heterogeneous disorder with diverse etiological factors and pathological
      features, a patient-centered integrative framework based on modifiable
      physiological and environmental factors may offer hope for more effective
      management and better clinical outcomes. An individualized approach may also help
      target interventions for subgroups most likely to respond to specific treatments.
      This review summarizes a number of avenues for integrative management, including
      dietary modification, functional nutritional deficiencies, physical fitness,
      psychological and physical stress, environmental toxicity, gastrointestinal
      disturbances, immunological aberrations, inflammation, oxidative stress, and
      mitochondrial dysfunction. A personalized, integrative approach to CFS/ME
      deserves further consideration as a template for patient management and future
      research. 

PMID- 24445355
TI  - Chronic fatigue syndrome, fibromyalgia, and myalgic encephalomyelitis: a clinical
      perspective.

PMID- 24445357
TI  - Edward Kondrot, MD: addressing the root causes of vision impairment through an
      energetic and holistic paradigm. Interview by Craig Gustafson.

PMID- 24445356
TI  - An innovative acupuncture treatment for primary dysmenorrhea: a randomized,
      crossover pilot study.
AB  - CONTEXT: Dysmenorrhea, the occurrence of painful menstrual cramping of the
      uterus, is a major cause of activity restriction and absences from school and
      work among young women. Standard pharmaceuticals used to treat dysmenorrhea are
      not effective for all women and have side effects that limit their use. Studies
      elsewhere have shown beneficial effects for use of vitamin K1 as an acupoint
      treatment, but the acceptability of this treatment to women in the United States
      has been unknown. OBJECTIVE: The study intended to examine the feasibility,
      acceptability, and preliminary effects of acupuncture point injection of vitamin
      K1 as an alternative treatment for primary dysmenorrhea among US women. DESIGN:
      The research team conducted a pilot study using a blinded, randomized, crossover
      trial design. SETTING: The study took place at the University of California, San
      Francisco (UCSF). PARTICIPANTS: The study was conducted in the San Francisco Bay
      Area among women 18 to 25 y of age who had been diagnosed with primary
      dysmenorrhea. Fourteen women completed all of the study's visits. INTERVENTION:
      Women with primary dysmenorrhea were randomized into 2 groups to receive
      bilateral injections of vitamin K1 in the Spleen-6 (SP-6) acupuncture point at
      the start of menstruation and then, following a 2-mo washout period, saline in a
      nonacupuncture point at the start of menstruation. One group received the vitamin
      K1 injection first, while the other group received the saline injection first.
      OUTCOME MEASURE: Dysmenorrhea pain intensity was measured using a 0-10 numeric
      rating scale (NRS), before and after injections. RESULTS: Women had an average
      2.5-point decrease in pain after a vitamin K1 injection in the SP-6 acupoint (P <
      .001), as compared with a 1.8-point decrease after a saline injection (P < .001).
      Change scores for vitamin K1, as compared with a saline injection, approached
      statistical significance (P < .10). Intensity and duration of menstrual symptoms,
      as measured by the Cox retrospective symptom scale, also decreased following
      injections. After participating, 94% of the women remained agreeable to receiving
      the injection therapy, and 77% reported they would come every month were the
      treatment available. CONCLUSIONS: Findings suggested high acceptability for an
      acupuncture point injection of vitamin K1 as treatment for primary dysmenorrhea
      among young women in San Francisco. Pain decreased with both treatments, with a
      trend toward greater pain reduction for the vitamin K1/SP-6 injection. This
      finding is consistent with outcomes from the Obstetrics and Gynecology Hospital
      in Shanghai, China, where the protocol was developed.

PMID- 24445358
TI  - A Royal Army Medical Corps doctor in World War I: the story of Captain John
      Clifford Metcalfe, MC.

PMID- 24445359
TI  - Biogenic catalysis in sulphide minerals' weathering processes and acid mine
      drainage genesis.
AB  - Bioleaching and biogenesis are the main outputs from a large group of
      environmental processes participating in the natural material cycle, used in raw
      materials processing. Bio-oxidation reactions are the main basis for bioleaching
      procedures, often participating in parallel leaching processes. During the
      leaching processes of polycomponent sulphide substrates, the factor of process
      selection also plays an important role, being in direct relation to the electric
      properties and galvanic effect occurring between the individual components of the
      leaching substrate. This work gives a summary of the results of a research
      focused on the possibilities of using biotechnological procedures for treatment
      of Slovak sulphide ores. The object of the research is extraction of valuable
      metals, undesirable admixtures and degradation of crystal lattice of sulphides
      for subsequent chemical leaching processing of precious metals. The results of
      experiments on the existence of biogenic processes in situ on waste dumps from
      exploitation containing residual sulphides are also presented. The processes
      result in acid mine drainage water generation. These waters are strongly
      mineralised (over 48 g/L) and of low pH; that is why they are very caustic. The
      arsenic content (2.558 mg/L) in outflowing waters from old mines is high and over
      the limits set by the law. 

PMID- 24445360
TI  - Expanding support for "upstream" surrogate decision making in the hospital.

PMID- 24445361
TI  - Genetic mutations in acute myeloid leukemia that influence clinical decisions.
AB  - PURPOSE OF REVIEW: A plethora of studies over the past two decades have
      identified many genes that are recurrently mutated in acute myeloid leukemia
      (AML). Although great advances have been made in understanding the role of these
      mutated genes in AML disease pathogenesis, to date relatively few have been
      demonstrated to have direct clinical relevance. RECENT FINDINGS: Genomic
      techniques have allowed for the identification of many mutated genes that appear
      to drive disease pathogenesis and prognosis in AML. Integrated analyses examining
      the co-occurrence of these genes in well annotated AML patient cohorts has helped
      to significantly refine prognostic models, allowing for a more nuanced selection
      of patients for optimal postremission therapies. Furthermore, there are emerging
      data that gene mutations may be useful to select patients for optimal doses
      and/or modalities of upfront AML therapy. Finally, mutated genes themselves hold
      promise as therapeutic targets, as supported by strong preclinical studies.
      SUMMARY: Recent advances in our knowledge of the molecular genetics of AML have
      significantly improved our tools for clinical decision-making and promise to
      identify new therapies for patients.

PMID- 24445362
TI  - Oscillatory shear stress induced calcium flickers in osteoblast cells.
AB  - The dynamic physical microenvironment of bone affects the activity of osteoblast
      cells, yet little is known about how osteoblast mechanotransduction depends on
      different features of a dynamic stimulus. Here we investigated the effect of
      physiologically relevant oscillatory flow shear stress on the calcium mobility in
      osteoblast cells within a microfluidic platform that mimics the confined
      environment of bone matrix. We characterized the spatiotemporal evolution of
      intracellular calcium 'flickers', an important signature of cell activation, in
      response to steady, pulsatile, and oscillatory shear stress. We found that
      oscillatory flow induces surprisingly higher flicker activity than other flow
      types. We could further attribute this phenomenon to the opening of a stretch
      activated ion channel, namely TRPM7. We also found that localization of TRPM7
      within the cholesterol-enriched lipid raft domains of plasma membranes is
      essential for its activity. Collectively our findings elucidated a candidate
      mechanism for the flow mediated stimulation of osteoblast cells. They therefore
      have implications towards unveiling various facets of bone formation and
      remodelling in healthy and diseased conditions, including bone-metastasis of
      various cancer types, diabetes, and inflammatory autoimmune diseases. 

PMID- 24445364
TI  - Trusting internal medicine in hard times.

PMID- 24445363
TI  - Effects of antioxidants on the quality and genomic stability of induced
      pluripotent stem cells.
AB  - Effects of antioxidants on the quality and genomic stability of induced
      pluripotent stem (iPS) cells were investigated with two human iPS cell lines
      (201B7 and 253G1). Cells used in this study were expanded from a single colony of
      each cell line with the addition of proprietary antioxidant supplement or
      homemade antioxidant cocktail in medium, and maintained in parallel for 2 months.
      The cells grew well in all culture conditions and kept "stemness". Although
      antioxidants modestly decreased the levels of intracellular reactive oxygen
      species, there were no differences in the expression of 53BP1 and pATM, two
      critical molecules related with DNA damage and repair, under various culture
      conditions. CGH analysis showed that the events of genetic aberrations were
      decreased only in the 253G1 iPS cells with the addition of homemade antioxidant
      cocktail. Long-term culture will be necessary to confirm whether low dose
      antioxidants improve the quality and genomic stability of iPS cells. 

PMID- 24445365
TI  - Role of protease inhibitor 9 in survival and replication of Mycobacterium
      tuberculosis in mononuclear phagocytes from HIV-1-infected patients.
AB  - OBJECTIVE AND DESIGN: Predisposition to opportunistic infections by Mycobacterium
      tuberculosis (MTB) is a concomitant of HIV-1 infection and occurrence of
      tuberculosis is independent of circulating CD4(+) T-cell count in HIV-1-infected
      patients. Infection of mononuclear phagocytes from healthy individuals by
      virulent MTB is associated with expression of the antiapoptotic molecule protease
      inhibitor 9 (PI-9), and PI-9 contributes to successful parasitism of macrophages
      by MTB. Here we studied the contribution of PI-9 to successful MTB infection of
      monocytes from HIV-1-infected patients. METHODS: Blood monocytes obtained from
      HAART-treated HIV-1-infected patients (HIV+) and healthy controls were assessed
      for support of MTB H37Rv growth by assessment of MTB 16S ribosomal (r)RNA in cell
      lysates on day 1 and day 7 by real-time reverse transcription-PCR. PI-9
      expression in monocyte cell lysates was assessed by ELISA and by reverse
      transcription-PCR. Inhibition of intracellular PI-9 was achieved by siRNA to PI-9
      and compared to control constructs. RESULTS: Monocytes from HIV-infected patients
      supported higher MTB growth [MTB 16S rRNA (d7/d1)] as compared with monocytes
      from healthy controls. Both PI-9 protein and mRNA were significantly higher in
      monocytes from HIV-infected patients as compared with healthy controls. PI-9
      protein levels prior to MTB infection correlated with MTB replication on day 7,
      and with plasma soluble CD14 levels. Silencing of PI-9 by transfection of
      monocytes from HIV-1-infected patients with PI-9-specific siRNA prior to
      infection improved intracellular containment of MTB. CONCLUSION: Increased
      intracellular PI-9 activity in mononuclear phagocytes from HIV-infected patients
      contributes to successful intracellular infection by virulent MTB.

PMID- 24445366
TI  - The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and
      other retroviruses.
AB  - Many microorganisms including retroviruses suppress the immune system of the
      infected host in order to maintain infection. Unfortunately, it is still unclear
      how retroviruses induce immunosuppression. There is increasing evidence of a
      common mechanism based on their transmembrane envelope proteins. This review
      therefore summarizes evidence of the involvement of the transmembrane envelope
      proteins in the immunopathogenesis of different retroviruses including HIV-1.
      Mutations in the immunosuppressive (isu) domain of the transmembrane envelope
      protein of several retroviruses abrogate the immunosuppressive activities in
      vitro and in vivo. Most importantly, virus sequences with such abrogating
      mutations were never found in HIV-1-infected individuals despite the fact that
      the mutated viruses are replication-competent. However, there is also evidence
      for additional, perhaps even divergent, strategies for each retrovirus. For
      example, in contrast to many other retroviruses, the HIV directly interacts with
      immune cells and infects them. In addition, HIV uses several accessory proteins
      to evade the immune response. Furthermore, the possible contribution of the
      transmembrane envelope proteins of endogenous retroviruses to immunosuppression
      when expressed on tumor cells or in the placenta is analyzed. 

PMID- 24445367
TI  - Renal events among women treated with tenofovir/emtricitabine in combination with
      either lopinavir/ritonavir or nevirapine.
AB  - OBJECTIVES: Tenofovir disoproxil fumarate (TDF) has been associated with renal
      insufficiency. Co-administration with boosted protease inhibitors, which
      increases its exposure, may further increase the risk of renal insufficiency.
      METHODS: We compared the incidence of renal events among women taking TDF co
      administered with lopinavir/ritonavir (LPV/r) versus those co-administering TDF
      with nevirapine (NVP). Renal events were defined as a confirmed drop in
      creatinine clearance associated with a serum creatinine grade 2 or higher, or
      that leading to treatment modification. RESULTS: Overall, 741 HIV-infected women
      were enrolled into the study. Of these, 24 (3.2%) had reportable renal events (18
      in LPV/r arm, six in NVP arm). In multivariate analysis, renal events were
      significantly associated with the LPV/r arm [odds ratio (OR) 3.12, 95% confidence
      interval (CI) 1.21, 8.05; P = 0.019], baseline HIV-1 RNA (OR 2.65, 95% CI 1.23,
      5.69 per 1 log10 copies/ml higher; P = 0.013) and baseline creatinine clearance
      (OR 0.83, 95% CI 0.70-0.98 per 10 ml/min higher; P = 0.030). In multivariate
      analysis evaluating renal events requiring treatment modification, only baseline
      HIV-1 RNA and creatinine clearance were significantly associated (OR 4.41, 95% CI
      1.65, 11.78 per 1 log10 copies/ml higher; P = 0.003 and OR 0.80, 95% CI 0.64,
      0.99 per 10 ml/min higher; P = 0.040, respectively). CONCLUSION: The rates of
      renal events were relatively low in the two treatment arms. However, patients
      taking TDF co-administered with LPV/r had significantly more renal events
      compared to those co-administered with NVP. Furthermore, higher baseline HIV RNA
      and lower creatinine clearance were associated with the development of renal
      insufficiency requiring treatment modification.

PMID- 24445368
TI  - Specific loss of cellular L-selectin on CD4(+) T cells is associated with
      progressive multifocal leukoencephalopathy development during HIV infection.
AB  - HIV(+) progressive multifocal leukoencephalopathy (PML) patients had a
      significantly lower expression of CD62L on CD4(+) T cells (P < 0.001) when
      compared with HIV(+) patients who did not develop PML. CD62L expression on CD4(+)
      T cells did not correlate with parameters such as CDC stage, CD4(+) cell
      percentage (of total CD3(+) T cells), CD4(+) cell counts, virus count, or
      clinical parameters. Measurement of CD62L might provide a biomarker for PML risk
      and could prompt a treatment change and/or close monitoring.

PMID- 24445369
TI  - RASP: rapid and robust backbone chemical shift assignments from protein
      structure.
AB  - Chemical shift prediction has an unappreciated power to guide backbone resonance
      assignment in cases where protein structure is known. Here we describe Resonance
      Assignment by chemical Shift Prediction (RASP), a method that exploits this power
      to derive protein backbone resonance assignments from chemical shift predictions.
      Robust assignments can be obtained from a minimal set of only the most sensitive
      triple-resonance experiments, even for spectroscopically challenging proteins.
      Over a test set of 154 proteins RASP assigns 88 % of residues with an accuracy of
      99.7 %, using only information available from HNCO and HNCA spectra. Applied to
      experimental data from a challenging 34 kDa protein, RASP assigns 90 % of
      manually assigned residues using only 40 % of the experimental data required for
      the manual assignment. RASP has the potential to significantly accelerate the
      backbone assignment process for a wide range of proteins for which structural
      information is available, including those for which conventional assignment
      strategies are not feasible. 

PMID- 24445370
TI  - The global north: HIV epidemiology in high-income countries.
AB  - PURPOSE OF REVIEW: The epidemiology of HIV epidemics provides the roadmap for
      prioritization of programmes and serves over time to evaluate broadly the
      successes and challenges in prevention. The purpose of this review was to
      summarize recent information about the epidemiology of HIV in high-income
      countries with concentrated HIV epidemics. RECENT FINDINGS: Data from 26
      countries were organized and analysed, and a systematic review of published
      literature relating to epidemiology in these countries was conducted. Our major
      findings illustrated strong patterns in epidemiology by mode of HIV acquisition:
      in most high-income countries, new HIV diagnoses attributable to male-female sex
      have been stable or decreasing, whereas new HIV diagnoses attributable to male
      male sex have been stable or increasing. Late diagnoses of HIV infection are
      common. Prevalence of HIV in high-income countries has risen over the past 5
      years as death rates have been stable or decreasing. Reports of the epidemiology
      of HIV among sex workers and transgendered persons are rare. SUMMARY: The
      epidemiology of HIV in high-income countries in 2013 depicts both the successes
      and challenges of HIV prevention. The stable to decreasing death rates and stable
      or declining trends in heterosexual populations are likely attributable, at least
      in part, to the broader availability of effective treatments for HIV and
      relatively broad availability of antiretroviral treatment in these countries.
      However, late diagnoses undermine the individual and public health value of
      antiretroviral treatment, and epidemics of HIV among MSM remain largely
      uncontrolled despite broad availability and coverage of treatment.

PMID- 24445371
TI  - The epidemiology of HIV among men who have sex with men in countries with
      generalized HIV epidemics.
AB  - PURPOSE OF REVIEW: Key populations at high risk for HIV acquisition and
      transmission, such as MSM, have long been identified as essential subpopulations
      for epidemiological surveillance of the HIV epidemic. However, surveillance
      systems in the context of generalized and widespread HIV epidemics have
      traditionally excluded these men. RECENT FINDINGS: Emerging and consistent data
      highlight the disproportionate burden of HIV among MSM that exists when compared
      with other men of reproductive age across countries with generalized epidemics.
      Correlates of prevalent HIV infection include individual-level determinants of
      HIV acquisition and transmission similar to that found in concentrated HIV
      epidemics and community-level structural factors, such as stigma, being
      blackmailed, and history of homophobic abuse. HIV incidence was only available
      from two countries (Kenya, Thailand) with generalized HIV epidemics, but in both
      settings was an order of magnitude higher than that of other populations.
      SUMMARY: The data presented here suggest that the dynamics of HIV infection among
      men are more similar across the world than they are different. Many HIV epidemics
      among average-risk reproductive age adults are slowing across both generalized
      and concentrated settings. It is in this context that high HIV incidence is
      observed among MSM, especially young MSM. This trend suggests a change in the
      trajectory of these HIV epidemics, a change that we may miss if we continue to
      understudy these populations based on unproved and dated assumptions.

PMID- 24445372
TI  - The emerging face of the HIV epidemic in the Middle East and North Africa.
AB  - PURPOSE OF REVIEW: A volume of quality HIV data has materialized recently in the
      Middle East and North Africa (MENA). This review provides a thematic narrative of
      the patterns of HIV infection transmission in this region in light of these data.
      RECENT FINDINGS: Tens of integrated bio-behavioral surveillance surveys among
      hard-to-reach key populations at higher risk have been conducted in MENA in the
      recent years. Many of the studies reported appreciable and growing HIV
      prevalence. A few studies found alarming prevalence of as much as 87.2% HIV
      prevalence among people who inject drugs in Tripoli, Libya. The discovery of
      these hitherto hidden epidemics was unsettling to some authorities after years in
      which the importance of a focus on HIV prevention among key populations was not
      recognized. SUMMARY: The new data from MENA indicate growing HIV epidemics among
      key populations across the region. There is heterogeneity, however, as to which
      key populations are affected and in what proportions in different countries. In a
      few countries, HIV appears to affect only one key population and often there is
      substantial geographical heterogeneity in HIV transmission. Data are indicative
      of a growing HIV disease burden in this part of the globe, in contrast with the
      declining epidemics in most other regions.

PMID- 24445373
TI  - A performance improvement initiative to determine the impact of increasing the
      time interval between changing centrally placed intravascular catheters.
AB  - Existing practice guidelines designed to minimize invasive catheter infections
      and insertion-related complications in general intensive care unit patients are
      difficult to apply to the burn population. Burn-specific guidelines for optimal
      frequency for catheter exchange do not exist, and great variation exists among
      institutions. Previously, the authors' practice was to follow a new site
      insertion at 48 hours by an exchange over a guidewire, which was followed 48
      hours later by a second guidewire exchange (48h group). As a performance
      improvement initiative, the authors attempted to determine whether there would be
      any advantage or disadvantage to extending these intervals to 72 hours (72h). All
      patients with centrally placed intravascular catheters from October 2007 to
      August 2008 were included in the 48h group, and all patients with catheters
      placed from September 2008 to December 2009 comprised the 72h group. Catheter
      infection rates were determined using the National Healthcare Safety Network
      definition for central line-associated bloodstream infections (CLABSIs) and
      calculated as CLABSIs/1000 catheter days. The two groups were not significantly
      different for age, sex, burn etiology, total burn size, or percent third-degree
      burn. There were 3.1 CLABSIs/1000 catheter days for the 48h group and 2.8
      CLABSIs/1000 catheter days for the 72h group (NS). The authors conclude that
      increasing the central catheter change interval from 48 to 72 hours did not
      result in any increase in their CLABSI rate. Implementation of this change in
      practice is expected to decrease supply costs by $28,000 annually in addition to
      reducing clinical support services needed to perform these procedures.

PMID- 24445374
TI  - Differential parsing of EGFR endocytic flux among parallel internalization
      pathways in lung cancer cells with EGFR-activating mutations.
AB  - Due to the existence of parallel pathways for receptor endocytosis and their
      complexities, a quantitative understanding of receptor endocytosis in normal and
      pathological settings requires computational analysis. Here, we develop a
      mechanistic model of epidermal growth factor receptor (EGFR) endocytosis to
      determine the relative contributions of three parallel pathways: clathrin
      dependent internalization mediated by mitogen-inducible gene 6 (MIG6), an
      endogenous EGFR kinase inhibitor that links EGFR to endocytic proteins; clathrin
      dependent internalization mediated by the ubiquitin ligase CBL, which can be
      sequestered by the regulatory protein Sprouty2; or alternative pathways that may
      be non-clathrin mediated. We applied the model to interpret our previous
      measurements of EGFR endocytosis in lung cancer cells. Interestingly, our results
      suggest that MIG6 is responsible for at least as much wild-type EGFR
      internalization as CBL, indicating that a significant fraction of internalizing
      EGFR may be incapable of driving signaling. Model results also suggest that
      MIG6's endocytic function is reduced for the kinase-activated and internalization
      impaired EGFR mutants found in some lung cancers. Analysis of Sprouty2 knockdown
      data indicates that Sprouty2 regulates EGFR endocytosis primarily by controlling
      EGFR expression, rather than by sequestering CBL, and supports the notion that
      CBL-mediated internalization is impaired for EGFR mutants. We further demonstrate
      that differences in internalization between wild-type and mutant EGFR cannot
      explain differences in EGF-mediated EGFR degradation without concomitant changes
      in EGFR recycling, which we previously quantified. This work provides new
      quantitative insights into EGFR trafficking in lung cancer and provides a
      framework for studying parallel endocytosis pathways for other receptors. 

PMID- 24445375
TI  - Scope and outcomes of surrogate decision making among hospitalized older adults.
AB  - IMPORTANCE: Hospitalized older adults often lack decisional capacity, but outside
      of the intensive care unit and end-of-life care settings, little is known about
      the frequency of decision making by family members or other surrogates or its
      implications for hospital care. OBJECTIVE: To describe the scope of surrogate
      decision making, the hospital course, and outcomes for older adults. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective, observational study conducted in medicine
      and medical intensive care unit services of 2 hospitals in 1 Midwestern city in
      1083 hospitalized older adults identified by their physicians as requiring major
      medical decisions. MAIN OUTCOMES AND MEASURES: Clinical characteristics, hospital
      outcomes, nature of major medical decisions, and surrogate involvement. RESULTS:
      According to physician reports, at 48 hours of hospitalization, 47.4% (95% CI,
      44.4%-50.4%) of older adults required at least some surrogate involvement,
      including 23.0% (20.6%-25.6%) with all decisions made by a surrogate. Among
      patients who required a surrogate for at least 1 decision within 48 hours, 57.2%
      required decisions about life-sustaining care (mostly addressing code status),
      48.6% about procedures and operations, and 46.9% about discharge planning.
      Patients who needed a surrogate experienced a more complex hospital course with
      greater use of ventilators (2.5% of patients who made decisions and 13.2% of
      patients who required any surrogate decisions; P < .001), artificial nutrition
      (1.7% of patients and 14.4% of surrogates; P < .001), and length of stay (median,
      6 days for patients and 7 days for surrogates; P < .001). They were more likely
      to be discharged to an extended-care facility (21.2% with patient decisions and
      40.9% with surrogate decisions; P < .001) and had higher hospital mortality (0.0%
      patients and 5.9% surrogates; P < .001). Most surrogates were daughters (58.9%),
      sons (25.0%), or spouses (20.6%). Overall, only 7.4% had a living will and 25.0%
      had a health care representative document in the medical record. CONCLUSIONS AND
      RELEVANCE: Surrogate decision making occurs for nearly half of hospitalized older
      adults and includes both complete decision making by the surrogate and joint
      decision making by the patient and surrogate. Surrogates commonly face a broad
      range of decisions in the intensive care unit and the hospital ward setting.
      Hospital functions should be redesigned to account for the large and growing role
      of surrogates, supporting them as they make health care decisions.

PMID- 24445376
TI  - The influence of obesity and overweight on medical costs: a panel data
      perspective.
AB  - This paper estimates the increase of direct medical costs of both severe and
      moderate obesity and overweight with respect to a normal-weight individual using
      a two-part generalised linear model and a longitudinal dataset of medical and
      administrative records of patients in primary and secondary healthcare centres
      followed up over seven consecutive years (2004-2010) in Spain. Our findings
      indicate that severe and moderate obesity imposes a substantial burden on the
      Spanish healthcare system. Specifically, being severely obese is associated with
      increases in medical costs of 26 % (instrumental variables (IV) estimate, 34 %)
      compared to a normal-weight individual. The effects of moderate obesity and
      overweight are more modest, raising medical costs by 16 % (IV estimate, 29 %) and
      8.5 % (IV estimate, 23 %), respectively. These changes in costs are slightly
      higher for those patients below the median age and for the women.
      Notwithstanding, the effects found in this study are comparatively much lower
      than that reported for the USA, based basically on a private healthcare system
      and characterised by a more obese population.

PMID- 24445377
TI  - Dietary proteins and angiogenesis.
AB  - Both defective and persistent angiogenesis are linked to pathological situations
      in the adult. Compounds able to modulate angiogenesis have a potential value for
      the treatment of such pathologies. Several small molecules present in the diet
      have been shown to have modulatory effects on angiogenesis. This review presents
      the current state of knowledge on the potential modulatory roles of dietary
      proteins on angiogenesis. There is currently limited available information on the
      topic. Milk contains at least three proteins for which modulatory effects on
      angiogenesis have been previously demonstrated. On the other hand, there is some
      scarce information on the potential of dietary lectins, edible plant proteins and
      high protein diets to modulate angiogenesis. 

PMID- 24445378
TI  - [Room tilt illusion: when everything seems to be upside down].

PMID- 24445379
TI  - An oral mixed fat load is followed by a modest anti-inflammatory adipocytokine
      response in overweight patients with metabolic syndrome.
AB  - We investigated the postprandial changes in plasma levels of adipocytokines in
      overweight patients with metabolic syndrome after an oral fat load. After an oral
      fat load and during a prolonged fast, blood was drawn at 0, 2, 3, 4 and 8 h for
      measurement of adiponectin, adipsin, cathepsin S, chemerin, hepatic growth
      factor, interferon-gamma-inducible protein-10, leptin, macrophage chemoattractant
      protein-1, macrophage migration inhibitory factor, nerve growth factor, retinol
      binding protein-4, resistin, serum amyloid A1, tissue inhibitor of
      metalloproteinase-1 and thrombopoietin using a microbead-based Luminex assay.
      Area under the curves (AUC) were calculated and compared. Plasma adiponectin
      levels were higher after an oral fat load compared to fasting at t = 2 h (950 +/-
      513 vs. -1,881 +/- 713 ng/ml) while the plasma levels for adipsin (-9 +/- 5 vs.
      16 +/- 5 ng/ml), chemerin (-122 +/- 35 vs. 13 +/- 21 ng/ml), SAA-1 (-391 +/- 213
      vs. 522 +/- 173 ng/ml) and TPO (-335 +/- 144 vs. 622 +/- 216 ng/ml) were lower
      after an oral fat load compared to fasting. The baseline corrected AUC for IP-10
      was higher after fat load compared to fasting (median -116 pg h/ml; IQR -270 to
      10 vs. -21 pg h/ml; IQR -136 to 418 (p = 0.047). In conclusion, in overweight
      male subjects with the metabolic syndrome, an oral fat load is accompanied with a
      modest anti-inflammatory response of adipose tissue-derived adipocytokines. 

PMID- 24445381
TI  - Kinematic and temporal factors associated with penetration-aspiration in
      swallowing liquids.
AB  - In this study we undertook careful analysis of 13 quantitative physiological
      variables related to oropharyngeal swallowing from a sample of 42 subacute
      patients referred for dysphagia assessment. Each patient underwent a
      videofluoroscopic swallowing examination in which they swallowed up to five
      boluses of 22 % w/v ultrathin liquid barium suspension administered by teaspoon.
      Our goal was to determine whether scores on 13 kinematic or temporal parameters
      of interest were independently associated with the presence of penetration
      aspiration in the final compiled dataset of 178 swallows. Participants were
      classified as aspirators based on the presence of at least one swallow that
      demonstrated a Penetration-Aspiration Scale score of >=3. The parameters of
      interest included six kinematic parameters for capturing hyoid position, three
      swallow durations [laryngeal closure duration, hyoid movement duration, and upper
      esophageal sphincter (UES) opening duration], and four swallow intervals
      (laryngeal closure to UES opening, bolus dwell time in the pharynx prior to
      laryngeal closure, stage transition duration, and pharyngeal transit time). Mixed
      model repeated-measures ANOVAs were conducted to determine the association
      between each parameter and aspiration status. Only 1 of the 13 parameters tested
      distinguished aspirators from nonaspirators: aspirators demonstrated
      significantly shorter UES opening duration. In addition, a trend toward reduced
      maximum superior position of the hyoid was seen in aspirators. Limitations and
      future considerations are discussed. 

PMID- 24445383
TI  - Direct force measurements on peeling heteropolymer ssDNA from a graphite surface
      using single-molecule force spectroscopy.
AB  - We report here a systematic investigation of the interactions between two
      heteropolymer DNA single-strands (ssDNA) and graphite surfaces using AFM-based
      single-molecule force spectroscopy (SMFS). For this purpose, force-displacement
      (FD) curves are recorded by peeling single-molecule ssDNA from graphite. We find
      that the unbinding forces are affected both by the DNA sequences and the ionic
      strength of the liquid environment. In particular, the unbinding force decreases
      with the increase of ionic strength. Dynamic force measurements indicate that the
      unbinding force increases nonlinearly with the logarithm of the applied loading
      rate. The force data at different loading rates can be fitted with a recently
      developed single-barrier adsorption model, which is used here as a mean of
      quantifying the differences in the adsorption between different sequences. In
      addition, we investigate the effect of DNA hybridization and the presence of
      mismatch pairing defects and find that flawless hybridization to a complementary
      oligomer significantly decreases the unbinding force but mismatched hybridization
      has no obvious effect on it. These results can help optimize a recently envisaged
      SMFS-based biosensing technology for label-free DNA detection. 

PMID- 24445382
TI  - Respiratory infections in acute stroke: nasogastric tubes and immobility are
      stronger predictors than dysphagia.
AB  - Swallowing problems occur in 37-78 % of stroke patients. Evidence points to
      multiple factors contributing to the development of pneumonia in the first week
      post stroke, of which the presence of dysphagia is one. A heightened
      understanding of the very acute phase (first 7 days post stroke) is required to
      improve management of this population. We conducted a retrospective review of 536
      stroke patients admitted to Australian hospitals in 2010. Data were collected on
      37 clinical and demographic parameters. Descriptive statistics and univariate and
      multivariate logistic regression analyses were performed. Dysphagia was present
      in 58.5 % of admissions. For those patients remaining in the study for the full
      week there was a recovery rate from dysphagia of 30.5 %. Overall incidence of
      respiratory infection was 11 %. Respiratory infections developed in 17 % of
      patients with dysphagia. Impaired Glasgow Coma Scale, ischemic stroke, and
      significantly impaired mobility were associated with swallowing difficulties.
      Being nil by mouth and insertion of a nasogastric tube were significant
      predictors for respiratory infections. This study of a large cohort of acute
      stroke patients supports research indicating that aspiration pneumonia is
      multifactorial in nature and the incidence of respiratory infection is
      significant in the very acute stroke period.

PMID- 24445384
TI  - Investigation of clinical characteristics as predictive factors for the humoral
      immune response to the influenza vaccine in patients with rheumatoid arthritis.
AB  - The objective of this observational study is to determine characteristics as
      predictive factors for the humoral immune response to the influenza vaccine in
      patients with rheumatoid arthritis (RA). Fifty-seven RA patients who visited our
      department between 2011 and 2012 were recruited for the present study. The anti
      influenza antibody titers of a trivalent influenza subunit vaccine
      (A/California/7/2009 (H1N1)-like strain (A/H1N1 strain), A/Victoria/210/2009
      (H3N2)-like strain (A/H3N2 strain), and B/Brisbane/60/2008-like strain (B
      strain)) were measured at baseline and 4 weeks after the vaccination using the
      hemagglutination inhibition assay. Associations between the immune response to
      the influenza vaccine and clinical characteristics such as background, clinical
      parameters, and "having treatments or not" were examined to determine predictive
      factors for the immune response to the influenza vaccine. The titers of the three
      strains were significantly increased in all RA patients after the influenza
      vaccination. Concerning predictive factors of the immune response, no significant
      differences were observed in background (age and sex) or clinical parameters
      (peripheral lymphocyte count, C-reactive protein, erythrocyte sedimentation rate,
      rheumatoid factor, matrix metalloproteinase-3, and disease activity score-28). No
      significant differences were observed in the titers of anti-influenza antibodies
      between the treatment (methotrexate, prednisolone, salazosulfapyridine, or
      tacrolimus) and no-treatment groups. In contrast, there was a significant
      difference in A/H3N2 strain between the patients with biologics and without
      biologics. The only factor that affected anti-influenza antibody titers was
      "having biologics or not"; therefore, the immune response to the influenza
      vaccine may not be predicted from the viewpoints of background and clinical
      parameters.

PMID- 24445385
TI  - Factors influencing the quality of life of Moroccan patients with juvenile
      idiopathic arthritis.
AB  - The aim of our study is to investigate the factors influencing the quality of
      life, assessed by the Pediatric Quality of Life Inventory 4.0 (PedsQL4) Generic
      Score Scales, in Moroccan patients with juvenile idiopathic arthritis. This is a
      cross-sectional study conducted between January and June 2012, covering children
      with juvenile idiopathic arthritis (JIA) seen at the consultations of El Ayachi
      Hospital and Children's Hospital of the University Hospital of Rabat. Quality of
      life is assessed by the PedsQL4 which is a questionnaire composed of 23 items,
      completed by the child and the parent; the response to each item ranges from 0 to
      100, so that higher scores indicate a better quality of life. The functional
      impact is assessed by the Childhood Health Assessment Questionnaire (CHAQ), and
      the disease activity by the number of tender and swollen joints, visual analogue
      scale (VAS) activity, erythrocyte sedimentation rate (ESR), and C-reactive
      protein. Forty-seven patients are included; the average age of the patients is 11
      +/- 3.35 years, and 40.4 % are females, with a median disease duration of 4 (2;
      6) years. The oligoarticular form presents 26.7 %, the systemic form 24.4 %, and
      the enthesic form 22.2 %. The median of PedsQL4 is 80.43 (63.19; 92.93), and the
      median of the CHAQ is 0 (0; 1). Our study shows that some clinical and biological
      characteristics have significant effects on PedsQL by both parent and child
      reports. This study suggests that the achievement of the quality of life of our
      patients with JIA depends on the disease activity measured by swollen joints, the
      number of awakenings, parent VAS, physician VAS, patient VAS, and the ESR. 

PMID- 24445387
TI  - Incidence and determinants of severe morbidity among HIV-infected patients from
      Rio de Janeiro, Brazil, 2000-2010.
AB  - BACKGROUND: Reliable information on severe morbidity is essential for identifying
      priorities for case management and to guide resource allocation within the health
      sector. METHODS: This study describes overall, AIDS- and non-AIDS-related severe
      morbidity as well as mortality and its determinants in an urban cohort of HIV
      infected individuals from a public healthcare institution, the Evandro Chagas
      Research Institute (IPEC) of the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
      Severe morbid events were defined as all clinical diagnoses listed in
      hospitalization discharge records; all diagnoses were checked and validated.
      Generalized estimating equation models were used to estimate incidence rates
      while adjusting for within-subject correlation. RESULTS: Between 2000 and 2010,
      3,537 patients were followed for a total of 16,960 person-years (PY) of follow
      up. Over the years, annual incidence rate of severe morbid events, AIDS-related
      events, non-AIDS-related events, and deaths significantly decreased from,
      respectively, 36.6, 12.9, 23.7 and 3.2 per 100 PY in 2000 to 25.3, 7.9, 17.4 and
      1.9 per 100 PY in 2010. Patients' immunological profiles significantly improved
      with time; 84% of the patients used combination antiretroviral therapy (cART) per
      year. Immunodeficiency was associated with a higher incidence rate of AIDS- and
      non-AIDS-related events as well as with the incidence rate of specific non-AIDS
      events (bacterial infections, toxicities, cardiovascular, renal and respiratory
      diseases). CONCLUSIONS: Our results show that in a middle income country with
      access to cART, non-AIDS-related events represent an important cause of severe
      morbidity alongside a still high incidence rate of AIDS-related events.

PMID- 24445386
TI  - Early-onset sarcoidosis caused by a rare CARD15/NOD2 de novo mutation and
      responsive to infliximab: a case report with long-term follow-up and review of
      the literature.
AB  - Granulomatous autoinflammatory diseases are monogenic syndromes caused by
      mutations in the region encoding for the nucleotide-binding domain region of the
      NOD2/CARD15 gene with subsequent dysregulation of the inflammatory response and
      formation of noncaseous granulomas. They include Blau syndrome (BS) and early
      onset sarcoidosis (EOS); both are clinically and genetically indistinguishable
      between them and they are the familial (autosomal dominantly inherited) and
      sporadic forms of the same disease, respectively. We describe a case of EOS,
      misdiagnosed for 30 years such as "juvenile rheumatoid arthritis" before and
      "classic sarcoidosis" later. In our patient, we found a new de novo mutation
      (E383G) in NOD2 that has been reported only in a family of Japanese patients with
      BS. After long-term follow-up (42 months), infliximab maintained good efficacy
      and safety without any sign of disease relapse and side effects.

PMID- 24445388
TI  - Electrofluorochromism in pi-conjugated ionic liquid crystals.
AB  - Materials in which photoluminescence is modulated by redox processes are known as
      electrofluorochromic. Intrinsically switchable fluorophores, incorporating both
      redox and fluorescent moieties, could be ideal electrofluorochromic materials if
      they possess high fluorescence quantum yields in at least one of their redox
      states. Fluorescent liquid crystals with redox active centres could combine the
      above requirements with the advantage to work in bulk anisotropic phases.
      However, electrofluorochromic liquid crystals have not been reported yet because
      their synthesis is challenging due to aggregation-caused fluorescent quenching.
      Here we show the first examples of electrofluorochromic pi-conjugated ionic
      liquid crystals based on thienoviologens. These ordered materials, combining
      ionic and electronic functions, are highly fluorescence in the bulk state
      (quantum yield>60%). Their direct electrochemical reduction leads to fast and
      reversible bulk electrofluorochromic response in both columnar and smectic phases
      allowing for fluorescence intensity modulation and colour tuning. 

PMID- 24445389
TI  - Transcervical intrauterine levobupivacaine or lidocaine infusion for pain control
      during endometrial biopsy.
AB  - BACKGROUND: Endometrial biopsy is a common procedure for the investigation of
      many gynecological disorders including abnormal uterine bleeding, postmenopausal
      bleeding, abnormal cytology and infertility. Most women experience some degree of
      discomfort and pain during the procedure. Pain may occur during dilation of the
      cervix for insertion of the catheter and during endometrial biopsy, which further
      aggravates pain by inducing uterine contraction. OBJECTIVES: To determine pain
      levels during endometrial biopsy by comparing intrauterine instillation of
      levobupivacaine or lidocaine with placebo in a randomized, double-blinded trial
      in pre- and postmenopausal women. METHODS: Ninety patients were allocated to
      either control or experimental groups before endometrial biopsy. The trial
      medication was intrauterine anesthesia, either 5 mL 0.9% saline (control group),
      or 5 mL 0.5% levobupivacaine or 2% lidocaine (experimental groups). Resident
      doctors used the same endometrial biopsy technique to minimize the risk of
      technical variation. All tissue specimens were sent for cytopathological
      examination. The pathologists, who were blinded to the study solution, analyzed
      all tissue specimens. The primary outcome measure was pain experienced during the
      procedure. Pain was assessed using a 10 cm visual analogue pain scale. All
      observed adverse effects were recorded until the patients were discharged.
      RESULTS: Pain scores of the intrauterine lidocaine and levobupivacaine groups
      were found to be significantly lower than the control group. There was no
      difference between the levobupivacaine and lidocaine groups with regard to pain
      scores. There was a moderately positive correlation between pain scores and
      endometrial thickness. No complications were observed due to the procedure. Most
      of the biopsy results were proliferative and secretory endometrium. Insufficient
      material causing inconclusive results was observed mostly in the control group.
      CONCLUSION: Transcervical intrauterine topical instillation of levobupivacaine or
      lidocaine causes pain relief during endometrial biopsy. However, further studies
      are needed to evaluate the effectiveness of intrauterine anesthesia, to determine
      optimal concentration, volume and waiting time according to the type of local
      anesthetic agent, and to assess the applicability of the method to other
      intrauterine procedures.

PMID- 24445390
TI  - Hypertension and overweight/obesity in Ghanaians and Nigerians living in West
      Africa and industrialized countries: a systematic review.
AB  - CONTEXT: There is a growing prevalence of cardiovascular disease (CVD) risk
      factors in West Africa and among its migrants to industrialized countries.
      Despite this, no study has reviewed CVD risk factor prevalence among West
      Africans in Africa and industrialized countries. OBJECTIVE: To appraise studies
      on the prevalence of two CVD risk factors (hypertension and overweight/obesity)
      among two major West African populations (Ghanaians and Nigerians) in Africa and
      industrialized countries. METHODS: A comprehensive literature search from 1996 to
      July 2012 was undertaken to identify quantitative studies on hypertension and
      overweight/obesity among adult Ghanaians and Nigerians in West Africa and
      industrialized countries. RESULTS: Twenty studies were included with 10 conducted
      in Ghana, six conducted in Nigeria and four in industrialized countries. Studies
      in Ghana and Nigeria reported a hypertension prevalence of 19.3-54.6% with
      minimal differences between rural, urban, semi-urban, and mixed populations. Of
      the hypertensive patients, 14-73% were aware of their condition, 3-86% were on
      treatment, and 2-13% had controlled blood pressures. Overweight/obesity
      prevalence in Ghana and Nigeria ranged from 20 to 62% and 4 to 49%, respectively.
      The four studies in industrialized countries reported a hypertension prevalence
      of 8.4-55% and overweight/obesity prevalence of 65.7-90%. CONCLUSION:
      Hypertension and overweight/obesity are highly prevalent conditions in West
      Africa and in its migrants residing in industrialized countries. Urgent measures
      are needed to prevent CVD risk factors and halt the clinical sequelae.

PMID- 24445391
TI  - Measurement of plasma renin concentration instead of plasma renin activity
      decreases the positive aldosterone-to-renin ratio tests in treated patients with
      essential hypertension.
AB  - BACKGROUND: The plasma aldosterone-to-renin ratio (ARR) for the diagnosis of
      primary aldosteronism is normally calculated with plasma renin activity (PRA) as
      denominator. However, new direct renin assays that measure plasma renin
      concentration (PRC) are progressively replacing PRA because these are faster,
      simpler, and more reproducible. OBJECTIVE: To assess whether the calculation of
      ARR with a direct assay (ARRD, ng/dl/mU/l) instead of PRA (ARRP, ng/dl/ng/ml/h)
      affects the rate of positive tests in patients on liberal antihypertensive
      treatment. DESIGN AND PARTICIPANTS: PRA, PRC, and plasma aldosterone
      concentration (PAC) were measured in 88 patients with essential hypertension,
      both in the supine position and after 60 min of active standing while on
      treatment with a variety of antihypertensive medications. The same measurements
      were carried out, for comparison, in 10 patients with proven aldosterone
      producing adenoma. SETTING: Single center, outpatient hypertension clinic in a
      tertiary care hospital. RESULTS: In patients with essential hypertension, median
      ARRP was 12 (range 0-71) in the supine position and 13 (range 0-80) after
      standing. The corresponding values of ARRD were 0.4 (range 0.01-3) and 0.5 (range
      0.02-7.8). Between ARRP and ARRD, there was a linear, highly significant
      relationship both in supine and standing position (r=0.88 and r=0.92,
      respectively). Using as threshold of normalcy for ARRP a value less than 30, as
      it is recommended by guidelines, there were 13 (15%) and 18 (20%) false
      positives, respectively in supine and standing position, whereas with the
      threshold of 3.7 for ARRD, there were no false positives in recumbent position
      and four (5%) after standing. Accordingly, the specificity of ARRP was 0.85 and
      0.78 and that of ARRD 1 and 0.95. In 10 patients with primary aldosteronism,
      median supine ARRP was 298 (range 48-1222) and ARRD 34 (range 2.8-244). Among
      these patients, no false negatives were found with ARRP and just one with ARRD.
      CONCLUSION: The rate of positive tests calculating ARR with PRC is lower than
      with PRA, the lower rate being found in patients studied in the recumbent
      position and apparently it is not affected by ongoing antihypertensive treatment.

PMID- 24445392
TI  - Oscillometric 24-h ambulatory blood pressure reference values in Hong Kong
      Chinese children and adolescents.
AB  - OBJECTIVES: We aimed to establish community-based normal reference values of 24-h
      ambulatory blood pressure monitoring (ABPM) for Chinese children and adolescents.
      Furthermore, we investigated how excluding overweight children affects BP
      percentiles and compared them with German references. METHODS: In this territory
      wide cross-sectional prospective cohort study, 1445 Hong Kong Chinese children
      and adolescents aged 8-17 years with body height between 119 and 185 cm were
      recruited. Their ABPM assessment was performed using validated arm oscillometric
      recorders (A&D TM-2430) and complied with American Heart Association's
      recommendations. The reference tables were constructed using the LMS method to
      normalize skewed distribution of ABP data to sex and age or height. RESULTS: The
      ambulatory BP was higher among boys and the difference between boys and girls
      progressively widened with age. An increasing trend in daytime and night-time SBP
      and DBP with age and height was observed in both sexes. The age-specific and sex
      specific 95th percentiles from nonoverweight children (n=1147; 79%) were lower
      than the whole cohort by up to 2.5 and 1 mmHg for SBP and DBP, respectively. In
      comparison, our overall and nonoverweight reference standards were generally
      higher than corresponding German references. CONCLUSION: The study provides
      ambulatory BP standards for Chinese children, with sex-related age-specific and
      height-specific percentiles. Further longitudinal studies are required for
      investigating its clinical utility in Chinese.

PMID- 24445393
TI  - A reduced heart rate variability is independently associated with a blunted
      nocturnal blood pressure fall in patients with resistant hypertension.
AB  - BACKGROUND: A blunted nocturnal blood pressure (BP) fall is a marker of worse
      cardiovascular outcomes, and autonomic imbalance may be involved. The objective
      was to evaluate the associations between the nocturnal BP fall and heart rate
      variability (HRV) parameters in resistant hypertension. DESIGN AND METHODS: In a
      cross-sectional analysis, 424 resistant hypertensive patients performed 24-h
      ambulatory BP and Holter monitoring, and 221 patients also performed
      polysomnography. Time-domain HRV parameters evaluated were the standard deviation
      of all normal RR intervals (SDNN), the standard deviation of the averaged normal
      RR intervals for all 5-min segments (SDANN), the root mean square of differences
      between adjacent R-R intervals (rMSSD) and the percentage of adjacent R-R
      intervals that varied by more than 50 ms (pNN50). Multivariate linear and
      logistic regressions assessed associations between the nocturnal BP fall and HRV
      parameters. RESULTS: Two hundred and sixty-six patients (63%) presented a
      nondipping pattern. These patients had lower SDNN and SDANN than normal dipping
      patients, but equal rMSSD and pNN50. On multivariate analysis, after adjustments
      for several confounders, a reduced SDNN (<70 ms) implied a 2.9 to 3.4-fold [95%
      confidence interval (CI) 1.2-8.5] and a reduced SDANN (<50 ms) a 3.7 to 4.2-fold
      (95% CI 1.5-11.4) higher odds of having a nondipping pattern. Further adjustment
      for the presence and severity of obstructive sleep apnoea did not change the
      results. CONCLUSION: Reduced SDNN and SDANN, two HRV parameters that mainly
      reflect sympathetic overactivity, were independently associated with a blunted
      nocturnal BP fall in resistant hypertension. These relationships offer insight
      into physiopathological mechanisms linking the circadian BP variability to
      cardiovascular outcomes.

PMID- 24445394
TI  - Chiral-like tunneling of electrons in two-dimensional semiconductors with Rashba
      spin-orbit coupling.
AB  - The unusual tunneling effects of massless chiral fermions (mCF) and massive
      chiral fermions (MCF) in a single layer graphene and bilayer graphene represent
      some of the most bizarre quantum transport phenomena in condensed matter system.
      Here we show that in a two-dimensional semiconductor with Rashba spin-orbit
      coupling (R2DEG), the real-spin chiral-like tunneling of electrons at normal
      incidence simultaneously exhibits features of mCF and MCF. The parabolic branch
      of opposite spin in R2DEG crosses at a Dirac-like point and has a band turning
      point. These features generate transport properties not found in usual two
      dimensional electron gas. Albeit its pi Berry phase, electron backscattering is
      present in R2DEG. An electron mimics mCF if its energy is in the vicinity of the
      subband crossing point or it mimics MCF if its energy is near the subband minima.

PMID- 24445395
TI  - Strong ferromagnetism at the surface of an antiferromagnet caused by buried
      magnetic moments.
AB  - Carrying a large, pure spin magnetic moment of 7 MUB per atom in the half-filled
      4f shell, divalent europium is an outstanding element for assembling novel
      magnetic devices in which a two-dimensional electron gas may be polarized due to
      exchange interaction with an underlying magnetically-active Eu layer. Here we
      show that the Si-Rh-Si surface trilayer of the antiferromagnet EuRh2Si2 bears a
      surface state, which exhibits an unexpected and large spin splitting controllable
      by temperature. The splitting sets in below ~32.5 K, well above the ordering
      temperature of the Eu 4f moments (~24.5 K) in the bulk, indicating a larger
      ordering temperature in the topmost Eu layers. The driving force for the
      itinerant ferromagnetism at the surface is the aforementioned exchange
      interaction. Such a splitting may also be induced into states of functional
      surface layers deposited onto the surface of EuRh2Si2 or similarly ordered
      magnetic materials with metallic or semiconducting properties. 

PMID- 24445396
TI  - High-level managers' considerations for RFID adoption in hospitals: an empirical
      study in Taiwan.
AB  - Prior researches have indicated that an appropriate adoption of information
      technology (IT) can help hospitals significantly improve services and operations.
      Radio Frequency Identification (RFID) is believed to be the next generation
      innovation technology for automatic data collection and asset/people tracking.
      Based on the Technology-Organization-Environment (TOE) framework, this study
      investigated high-level managers' considerations for RFID adoption in hospitals.
      This research reviewed literature related IT adoption in business and followed
      the results of a preliminary survey with 37 practical experts in hospitals to
      theorize a model for the RFID adoption in hospitals. Through a field survey of
      102 hospitals and hypotheses testing, this research identified key factors
      influencing RFID adoption. Follow-up in-depth interviews with three high-level
      managers of IS department from three case hospitals respectively also presented
      an insight into the decision of RFID's adoption. Based on the research findings,
      cost, ubiquity, compatibility, security and privacy risk, top management support,
      hospital scale, financial readiness and government policy were concluded to be
      the key factors influencing RFID adoption in hospitals. For practitioners, this
      study provided a comprehensive overview of government policies able to promote
      the technology, while helping the RFID solution providers understand how to
      reduce the IT barriers in order to enhance hospitals' willingness to adopt RFID. 

PMID- 24445397
TI  - TGF-beta upregulates miR-182 expression to promote gallbladder cancer metastasis
      by targeting CADM1.
AB  - Transforming growth factor beta (TGF-beta) plays important roles in tumor
      metastasis by regulating miRNAs expression. miR-182 is an important molecule in
      the regulation of cancer progression. The aim of the study is to assess the role
      of miR-182 in TGF-beta-induced cancer metastasis. In the present study, we found
      that miR-182 levels are significantly upregulated in GBC tissues compared with
      normal controls, and miR-182 expression is remarkably increased in primary tumors
      that subsequently metastasized, when compared to those primary tumors that did
      not metastasize. TGF-beta induces miR-182 expression in GBC cells, and
      overexpression of miR-182 promotes GBC cell migration and invasion, whereas miR
      182 inhibition suppresses TGF-beta-induced cancer cell migration and invasion.
      The blockage of miR-182 by a specific inhibitor effectively inhibits pulmonary
      metastases in vivo. We further identified that the cell adhesion molecule1
      (CADM1) is a new target gene of miR-182. miR-182 negatively regulates CADM1
      expression in vitro and in vivo. Importantly, re-expression of CADM1 in GBC cells
      partially abrogates miR-182-induced cell invasion. CONCLUSIONS: miR-182 is an
      important mediator of GBC metastasis, thus offering a new target for the
      development of therapeutic agents against GBC.

PMID- 24445398
TI  - An assessment of the dementia CQUIN--an audit of improving compliance.
AB  - The Department of Health has increased the emphasis on earlier detection of
      dementia among patients aged over 75 admitted to hospital in an emergency in
      England. Introduction of a Commissioning for Quality and Innovation (CQUIN)
      payment provides an incentive for NHS Trusts to screen patients for memory
      problems on admission. This article reports on how improvements were made to the
      screening process across three wards in a large university teaching hospital.

PMID- 24445399
TI  - Implementation of advanced practice nurse clinic for management of behavioral
      symptoms in dementia: a dyadic intervention (innovative practice).
AB  - Behavioral symptoms are common in all types of dementia and often result in
      significant caregiver stress and illness, institutionalization of the patient,
      and reduced quality of life for the patient and caregiver. Health care
      practitioners often lack the expertise or time to adequately assess behavioral
      symptoms or counsel caregivers about interventions. Our goal was to implement a
      specialty clinic managed by advanced practice nurses to assess and manage
      behavioral symptoms associated with dementia. The clinic evaluations consisted of
      an assessment of the patient by the Nurse Practitioner during the time that the
      family caregiver(s) was interviewed by the Clinical Nurse Specialist and focused
      on an assessment of the cognitive and functional abilities of the patient,
      identification of triggers for the problematic behaviors, and assessment of
      caregiver coping. We evaluated 66 dyads since implementation in February 2010.
      The patients were primarily female, Caucasian, 74.3 years of age with Alzheimer's
      disease. The majority of caregivers were spouses (n = 44) followed by adult
      children (n = 20) and then siblings (n = 2). Targeted interventions were
      developed and caregiver counseling, support, and education were an integral part
      of the consultation and included written information, video instruction, and
      internet resources. Evaluations indicated caregivers and referring providers
      found the appointment helpful in managing behavioral symptoms and caregiver
      stress. 

PMID- 24445400
TI  - Foetal alcohol spectrum disorder: identifying the neurobehavioural phenotype and
      effective interventions.
AB  - PURPOSE OF REVIEW: Since the first description of the foetal damage of alcohol in
      1967, numerous studies have outlined different aspects of neurodevelopmental
      dysfunction, adversely affecting the lives of children worldwide. Although the
      cause of the syndrome is sorted out, the pathogenesis of brain damage is far from
      being clear. In contrast to children exhibiting the full facial dysmorphology,
      who are relatively easy to diagnose, in those presenting only with alcohol
      related neurodevelopmental damage diagnosis is much more challenging due to poor
      specificity of the brain dysfunction. Hence, identifying the neurodevelopmental
      phenotype of foetal alcohol spectrum disorder (FASD) is a major challenge. RECENT
      FINDINGS: Recently, a behavioural phenotype of FASD has been described and
      validated using items from the Child Behaviour Checklist. This tool has high
      sensitivity and specificity in separating children with FASD from those with ADHD
      and from healthy controls. In parallel, a number of intervention studies show
      promise in improving the abilities of children and adolescents with the syndrome
      to cope with daily tasks and improve their quality of life. SUMMARY: The
      neurobehavioural screening test can facilitate screening for FASD and is an
      official screening tool in the FASD toolkit of the Public Health Agency of
      Canada. Promising new interventions may attenuate the long-term outcome of these
      children.

PMID- 24445401
TI  - Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease?
AB  - PURPOSE OF REVIEW: We reviewed clinical trials on active and passive anti-beta
      amyloid (Abeta) immunotherapy for the treatment of Alzheimer's disease with a
      particular focus on monoclonal antibodies against Abeta. RECENT FINDINGS: Studies
      on anti-Alzheimer's disease immunotherapy published in the period from January
      2012 to October 2013 were reviewed. SUMMARY: Both active and passive anti-Abeta
      immunotherapies were shown to clear brain Abeta deposits. However, an active anti
      Abeta vaccine (AN1792) has been discontinued because it caused
      meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive
      immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's
      disease patients with bapineuzumab, a humanized monoclonal antibody directed at
      the N-terminal sequence of Abeta, were disappointing. Another antibody,
      solanezumab, directed at the mid-region of Abeta, failed in two Phase III
      clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase
      III study with solanezumab is ongoing in mildly affected Alzheimer's disease
      patients based on encouraging results in this subgroup of patients. Second
      generation active Abeta vaccines (ACC-001, CAD106, and Affitope AD02) and new
      passive anti-Abeta immunotherapies (gantenerumab and crenezumab) are being tested
      in prodromal Alzheimer's disease patients, in presymptomatic individuals with
      Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of
      developing Alzheimer's disease to definitely test the Abeta cascade hypothesis of
      Alzheimer's disease.

PMID- 24445402
TI  - Lifetime requirement of the methionine cycle for neuronal development and
      maintenance.
AB  - PURPOSE OF REVIEW: Nutrition exerts a pervasive impact on normal and pathological
      conditions of the nervous system. One critical pathway is the methionine cycle,
      in which folate and B12 convert homocysteine to methionine, which is in turn
      converted to S-adenosyl methionine (SAM; the major methyl donor). As a
      consequence of methylation, however, SAM is converted to the neurotoxin
      homocysteine and must be excreted or drawn back into the methionine cycle, which
      requires additional folate and B12. Dietary or genetic folate deficiency impairs
      this cycle, leading to developmental disorders, including those of the nervous
      system. RECENT FINDINGS: Folate and SAM exert profound epigenetic effects via DNA
      and histone methylation. Maternal supplementation during pregnancy has fostered
      an increase in individuals harboring genetic polymorphisms that compromise folate
      usage. Such individuals harbor a lifetime requirement for additional dietary
      folate, often not met beyond peri/postnatal periods. Herein, we consider the
      potential link of failure to meet this additional requirement to early and age
      related cognitive compromise. SUMMARY: Compromises in the methionine cycle can
      manifest as a spectrum of disorders throughout life. These considerations
      underscore how prenatal nutritional supplementation can alleviate developmental
      disorders by inadvertently establishing latent conditions that, in the absence of
      continued supplementation, may lead to age-related cognitive decline.

PMID- 24445403
TI  - Evaluation of indigenous microalgal isolate Chlorella sp. FC2 IITG as a cell
      factory for biodiesel production and scale up in outdoor conditions.
AB  - The present study reports evaluation of an indigenous microalgal isolate
      Chlorella sp. FC2 IITG as a potential candidate for biodiesel production.
      Characterization of the strain was performed under photoautotrophic,
      heterotrophic, and mixotrophic cultivation conditions. Further, an open-pond
      cultivation of the strain under outdoor conditions was demonstrated to evaluate
      growth performance and lipid productivity under fluctuating environmental
      parameters and in the presence of potential contaminants. The key findings were:
      (1) the difference in cultivation conditions resulted in significant variation in
      the biomass productivity (73-114 mg l-1 day-1) and total lipid productivity
      (35.02-50.42 mg l-1 day-1) of the strain; (2) nitrate and phosphate starvation
      were found to be the triggers for lipid accumulation in the cell mass; (3) open
      pond cultivation of the strain under outdoor conditions resulted in biomass
      productivity of 44 mg l-1 day-1 and total lipid productivity of 10.7 mg l-1 day
      1; (4) a maximum detectable bacterial contamination of 7 % of the total number of
      cells was recorded in an open-pond system; and (5) fatty acid profiling revealed
      abundance of palmitic acid (C16:0), oleic acid (C18:1) and linoleic acid (C18:2),
      which are considered to be the key elements for suitable quality biodiesel.

PMID- 24445404
TI  - Warfarin interactions with antibiotics in the ambulatory care setting.
AB  - IMPORTANCE: The effect of antibiotic coadministration on the international
      normalized ratio (INR) in a relatively stable, real-world warfarin population has
      not been adequately described. Case reports and studies of healthy volunteers do
      not account for the potential contribution of acute illness to INR variability.
      OBJECTIVE: To compare the risk of excessive anticoagulation among patients with
      stable warfarin therapy purchasing an antibiotic (antibiotic group) with the risk
      in patients purchasing a warfarin refill (stable controls) and patients with
      upper respiratory tract infection but not receiving an antibiotic (sick
      controls). DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal
      cohort study evaluated patients receiving warfarin between January 1, 2005, and
      March 31, 2011, at Kaiser Permanente Colorado, an integrated health care delivery
      system. Continuous data were expressed as mean (SD) or median (interquartile
      range). Multivariable logistic regression analysis was used to identify factors
      independently associated with a follow-up INR of 5.0 or more. A total of 5857
      (48.8%), 5579 (46.5%), and 570 (4.7%) patients were included in the antibiotic,
      stable control, and sick control groups, respectively. Mean age was 68.3 years,
      and atrial fibrillation was the most common (44.4%) indication for
      anticoagulation. EXPOSURES: Warfarin therapy with a medical visit for upper
      respiratory tract infection or coadministration of antibiotics. MAIN OUTCOMES AND
      MEASURES: Primary outcomes were the proportion of patients experiencing a follow
      up INR of 5.0 or more and change between the last INR measured before the index
      date and the follow-up INR. RESULTS: The proportion of patients experiencing an
      INR of 5.0 or more was 3.2%, 2.6%, and 1.2% for the antibiotic, sick, and stable
      groups, respectively (P < .001, antibiotic vs stable control group; P < .017,
      sick vs stable control group; P = .44, antibiotic vs sick control group). Cancer
      diagnosis, elevated baseline INR, and female sex predicted a follow-up INR of 5.0
      or more. Among antibiotics, those interfering with warfarin metabolism posed the
      greatest risk for an INR of 5.0 or more. CONCLUSIONS AND RELEVANCE: Acute upper
      respiratory tract infection increases the risk of excessive anticoagulation
      independent of antibiotic use. Antibiotics also increase the risk; however, most
      patients with previously stable warfarin therapy will not experience clinically
      relevant increases in INR following antibiotic exposure or acute upper
      respiratory tract infection.

PMID- 24445405
TI  - Modeling protein assemblies in the proteome.
AB  - Most (if not all) proteins function when associated in multimolecular assemblies.
      Attaining the structures of protein assemblies at the atomic scale is an
      important aim of structural biology. Experimentally, structures are increasingly
      available, and computations can help bridge the resolution gap between high- and
      low-resolution scales. Existing computational methods have made substantial
      progress toward this aim; however, current approaches are still limited. Some
      involve manual adjustment of experimental data; some are automated docking
      methods, which are computationally expensive and not applicable to large-scale
      proteome studies; and still others exploit the symmetry of the complexes and thus
      are not applicable to nonsymmetrical complexes. Our study aims to take steps
      toward overcoming these limitations. We have developed a strategy for the
      construction of protein assemblies computationally based on binary interactions
      predicted by a motif-based protein interaction prediction tool, PRISM (Protein
      Interactions by Structural Matching). Previously, we have shown its power in
      predicting pairwise interactions. Here we take a step toward multimolecular
      assemblies, reflecting the more prevalent cellular scenarios. With this method we
      are able to construct homo-/hetero-complexes and symmetric/asymmetric complexes
      without a limitation on the number of components. The method considers
      conformational changes and is applicable to large-scale studies. We also exploit
      electron microscopy density maps to select a solution from among the predictions.
      Here we present the method, illustrate its results, and highlight its current
      limitations. 

PMID- 24445406
TI  - A quantitative chemical proteomics approach to profile the specific cellular
      targets of andrographolide, a promising anticancer agent that suppresses tumor
      metastasis.
AB  - Drug target identification is a critical step toward understanding the mechanism
      of action of a drug, which can help one improve the drug's current therapeutic
      regime and expand the drug's therapeutic potential. However, current in vitro
      affinity-chromatography-based and in vivo activity-based protein profiling
      approaches generally face difficulties in discriminating specific drug targets
      from nonspecific ones. Here we describe a novel approach combining isobaric tags
      for relative and absolute quantitation with clickable activity-based protein
      profiling to specifically and comprehensively identify the protein targets of
      andrographolide (Andro), a natural product with known anti-inflammation and anti
      cancer effects, in live cancer cells. We identified a spectrum of specific
      targets of Andro, which furthered our understanding of the mechanism of action of
      the drug. Our findings, validated through cell migration and invasion assays,
      showed that Andro has a potential novel application as a tumor metastasis
      inhibitor. Moreover, we have unveiled the target binding mechanism of Andro with
      a combination of drug analog synthesis, protein engineering, and mass
      spectrometry-based approaches and determined the drug-binding sites of two
      protein targets, NF-kappaB and actin. 

PMID- 24445407
TI  - Hepatitis E in liver transplant recipients in the Rhone-Alpes region in France.
AB  - PURPOSE: In developed countries, hepatitis E virus (HEV) is considered an
      emerging pathogen, but prevalence seems highly variable according to previous
      European studies. As HEV can lead to chronic infections in immunosuppressed
      patients, it is thus essential to evaluate the prevalence and incidence of this
      infection. METHODS: We determined retrospectively, in a cohort of 206 pediatric
      and adult liver transplant recipients from the Rhone-Alpes region in France, pre
      transplant anti-HEV-IgG prevalence and incidence of HEV infections during post
      transplant follow-up (HEV IgG and IgM +/- HEV-RNA). RESULTS: Transplantations
      were carried out between 2005 and 2012 and mean post-transplant follow-up was
      32.8 months. Global pre-transplant prevalence of anti-HEV IgG was 29%, increasing
      regularly with age from 7% for children under 15 to 49% for patients older than
      60. From the 142 seronegative patients before transplant, 11 seroconversions
      (7.7%) were observed during follow-up (incidence of 2.83 cases per 100 person
      years). HEV RNA-tested at transaminases peak or randomly-was detected in only one
      case of seroconversion. For at least 2 HEV-seropositive patients, who had
      negative RNAemia before transplantation, viral RNA was detected chronically
      during follow-up, suggesting reinfection with HEV. CONCLUSION: Acute infections
      were largely more frequent than chronic infections and were asymptomatic or
      misdiagnosed, suggesting that liver transplant patients may not be particularly
      prone to developing severe HEV hepatitis. In addition, the presence of IgG anti
      HEV may not protect against re-infection. Serological testing, therefore, appears
      to be of limited interest for the diagnosis of HEV infections in liver transplant
      recipients.

PMID- 24445408
TI  - [Importance of nuclear medicine diagnostics in CUP syndrome].
AB  - CLINICAL/METHODICAL ISSUE: The diagnostic work-up in patients with carcinoma of
      unknown primary (CUP) syndrome is extensive, highly time-consuming and cost
      intensive and ultimately often fails to detect a primary site. STANDARD
      RADIOLOGICAL METHODS: In this context chest X-ray and computed tomography (CT)
      have been used as standard imaging modalities in CUP syndrome. METHODOLOGICAL
      INNOVATIONS: Since the introduction of positron emission tomography (PET)
      evaluation of tumor vitality has become possible. Furthermore, PET-CT hybrid
      scanners allow the combination of functional and morphological imaging.
      PERFORMANCE: Several meta-analyses have reported an additional overall detection
      rate between 24.5 % and 44 % by either PET or PET-CT. Metastatic localization
      (cervical versus extracervical) did not influence the performance. The
      sensitivity was usually high (> 80 %) but specificity was moderate ranging from
      68 % to 88 % at best. If mentioned, the results obtained by fluorodeoxyglucose
      (FDG)-PET significantly changed the clinical management in approximately one
      third of the patients studied. In a direct comparison with PET alone, PET-CT did
      not depict significantly more primary tumors but was able to reduce false
      positive findings. ACHIEVEMENTS: To determine the real additional value of PET-CT
      in the diagnosis of CUP syndrome large prospective studies with more uniform
      inclusion criteria are needed. Despite the capabilities of FDG-PET-CT there is as
      yet no evidence that a potentially improved diagnostic algorithm is translated
      into a better patient outcome. PRACTICAL RECOMMENDATIONS: Nevertheless, FDG-PET
      CT should be performed in all CUP patients where conventional imaging failed to
      detect a primary site or the results are equivocal. In CUP patients with cervical
      lymph node metastases PET-CT should be carried out prior to panendoscopy to
      reduce the number of false negative biopsies.

PMID- 24445409
TI  - [Passive smoking: 6 years of the Non-smoker Protection Act in Germany and the
      consequences].

PMID- 24445410
TI  - An exploratory study of adolescent pimping relationships.
AB  - In the last decade, public attention to the problem of commercially sexually
      exploited children (CSEC) has grown. This exploratory qualitative study examines
      adolescent pimping relationships, including how urban youth perceive these types
      of relationships. Study data stem from interviews with three young adult
      informants with first-hand knowledge of adolescent pimping, as well as three
      gender-specific focus group discussions with a convenience sample of 26 urban
      high school students who have first- or second-hand knowledge of adolescent
      pimping. Findings indicate that respondents believe teen pimping exists in their
      schools and communities, and that those exploited typically do not self-identify
      as victims. Respondents also believed that younger pimps are more likely to use
      violence to induce compliance among the girls they exploit, whereas older pimps
      are more likely to emotionally manipulate young women into exploitation. Further,
      respondents indicated that some young people agreed to exchange or sell sex for
      money as a favor to their boyfriends or girlfriends, and some young people
      believed that selling sex is acceptable under certain circumstances. The growing
      attention to CSEC provides an important opportunity to expand prevention efforts
      to reach those most affected and at risk for exploitation. The findings highlight
      critical areas for augmenting traditional content in school-based HIV/STI and
      sexuality education classes. 

PMID- 24445411
TI  - Ontology-driven monitoring of patient's vital signs enabling personalized medical
      detection and alert.
AB  - A major challenge related to caring for patients with chronic conditions is the
      early detection of exacerbations of the disease. Medical personnel should be
      contacted immediately in order to intervene in time before an acute state is
      reached, ensuring patient safety. This paper proposes an approach to an ambient
      intelligence (AmI) framework supporting real-time remote monitoring of patients
      diagnosed with congestive heart failure (CHF). Its novelty is the integration of:
      (i) personalized monitoring of the patients health status and risk stage; (ii)
      intelligent alerting of the dedicated physician through the construction of
      medical workflows on-the-fly; and (iii) dynamic adaptation of the vital signs'
      monitoring environment on any available device or smart phone located in close
      proximity to the physician depending on new medical measurements, additional
      disease specifications or the failure of the infrastructure. The intelligence
      lies in the adoption of semantics providing for a personalized and automated
      emergency alerting that smoothly interacts with the physician, regardless of his
      location, ensuring timely intervention during an emergency. It is evaluated on a
      medical emergency scenario, where in the case of exceeded patient thresholds,
      medical personnel are localized and contacted, presenting ad hoc information on
      the patient's condition on the most suited device within the physician's reach. 

PMID- 24445412
TI  - A smart kitchen for ambient assisted living.
AB  - The kitchen environment is one of the scenarios in the home where users can
      benefit from Ambient Assisted Living (AAL) applications. Moreover, it is the
      place where old people suffer from most domestic injuries. This paper presents a
      novel design, implementation and assessment of a Smart Kitchen which provides
      Ambient Assisted Living services; a smart environment that increases elderly and
      disabled people's autonomy in their kitchen-related activities through context
      and user awareness, appropriate user interaction and artificial intelligence. It
      is based on a modular architecture which integrates a wide variety of home
      technology (household appliances, sensors, user interfaces, etc.) and associated
      communication standards and media (power line, radio frequency, infrared and
      cabled). Its software architecture is based on the Open Services Gateway
      initiative (OSGi), which allows building a complex system composed of small
      modules, each one providing the specific functionalities required, and can be
      easily scaled to meet our needs. The system has been evaluated by a large number
      of real users (63) and carers (31) in two living labs in Spain and UK. Results
      show a large potential of system functionalities combined with good usability and
      physical, sensory and cognitive accessibility. 

PMID- 24445413
TI  - Incorporating beta-cyclodextrin with ZnO nanorods: a potentiometric strategy for
      selectivity and detection of dopamine.
AB  - We describe a chemical sensor based on a simple synthesis of zinc oxide nanorods
      (ZNRs) for the detection of dopamine molecules by a potentiometric approach. The
      polar nature of dopamine leads to a change of surface charges on the ZNR surface
      via metal ligand bond formation which results in a measurable electrical signal.
      ZNRs were grown on a gold-coated glass substrate by a low temperature aqueous
      chemical growth (ACG) method. Polymeric membranes incorporating beta-cyclodextrin
      (beta-CD) and potassium tetrakis (4-chlorophenyl) borate was immobilized on the
      ZNR surface. The fabricated electrodes were characterized by X-ray diffraction
      (XRD) and scanning electron microscopy (SEM) techniques. The grown ZNRs were well
      aligned and exhibited good crystal quality. The present sensor system displays a
      stable potential response for the detection of dopamine in 10(-2) mol.L(-1)
      acetic acid/sodium acetate buffer solution at pH 5.45 within a wide concentration
      range of 1 * 10(-6) M(-1) * 10(-1) M, with sensitivity of 49 mV/decade. The
      electrode shows a good response time (less than 10 s) and excellent
      repeatability. This finding can contribute to routine analysis in laboratories
      studying the neuropharmacology of catecholamines. Moreover, the metal-ligand
      bonds can be further exploited to detect DA receptors, and for bio-imaging
      applications.

PMID- 24445414
TI  - Statistical tools applied in the characterisation and evaluation of a thermo
      hygrometric corrective action carried out at the Noheda archaeological site
      (Noheda, Spain).
AB  - The Noheda archaeological site is unique and exceptional for its size, and the
      quality and conservation condition of the Roman mosaic pavement covering its
      urban pars. In 2008 a tent was installed as protection from rain and sun. Being
      of interest to characterise the microclimate of the remains, six probes with
      relative humidity and temperature sensors were installed in 2013 for this
      purpose. Microclimate monitoring allowed us to check relative humidity
      differences resulting from the groundwater level, as well as inner sensors
      reaching maximum temperatures higher than the outdoors ones as a consequence of
      the non-ventilated tent covering the archaeological site. Microclimatic
      conditions in the archaeological site were deemed detrimental for the
      conservation of the mosaics. Thus, in summer 2013, expanded clay and geotextile
      were installed over the mosaics as a corrective action. The outcomes of this
      study have proven the effectiveness of this solution to control temperature and
      relative humidity, helping to configure a more stable microclimate suitable for
      preservation of the mosaic. 

PMID- 24445415
TI  - Manufacture of radio frequency micromachined switches with annealing.
AB  - The fabrication and characterization of a radio frequency (RF) micromachined
      switch with annealing were presented. The structure of the RF switch consists of
      a membrane, coplanar waveguide (CPW) lines, and eight springs. The RF switch is
      manufactured using the complementary metal oxide semiconductor (CMOS) process.
      The switch requires a post-process to release the membrane and springs. The post
      process uses a wet etching to remove the sacrificial silicon dioxide layer, and
      to obtain the suspended structures of the switch. In order to improve the
      residual stress of the switch, an annealing process is applied to the switch, and
      the membrane obtains an excellent flatness. The finite element method (FEM)
      software CoventorWare is utilized to simulate the stress and displacement of the
      RF switch. Experimental results show that the RF switch has an insertion loss of
      0.9 dB at 35 GHz and an isolation of 21 dB at 39 GHz. The actuation voltage of
      the switch is 14 V. 

PMID- 24445416
TI  - Wireless displacement sensing enabled by metamaterial probes for remote
      structural health monitoring.
AB  - We propose and demonstrate a wireless, passive, metamaterial-based sensor that
      allows for remotely monitoring submicron displacements over millimeter ranges.
      The sensor comprises a probe made of multiple nested split ring resonators
      (NSRRs) in a double-comb architecture coupled to an external antenna in its near
      field. In operation, the sensor detects displacement of a structure onto which
      the NSRR probe is attached by telemetrically tracking the shift in its local
      frequency peaks. Owing to the NSRR's near-field excitation response, which is
      highly sensitive to the displaced comb-teeth over a wide separation, the wireless
      sensing system exhibits a relatively high resolution (<1 um) and a large dynamic
      range (over 7 mm), along with high levels of linearity (R2 > 0.99 over 5 mm) and
      sensitivity (>12.7 MHz/mm in the 1-3 mm range). The sensor is also shown to be
      working in the linear region in a scenario where it is attached to a standard
      structural reinforcing bar. Because of its wireless and passive nature, together
      with its low cost, the proposed system enabled by the metamaterial probes holds a
      great promise for applications in remote structural health monitoring. 

PMID- 24445417
TI  - Wearable gait measurement system with an instrumented cane for exoskeleton
      control.
AB  - In this research we introduce a wearable sensory system for motion intention
      estimation and control of exoskeleton robot. The system comprises wearable
      inertial motion sensors and shoe-embedded force sensors. The system utilizes an
      instrumented cane as a part of the interface between the user and the robot. The
      cane reflects the motion of upper limbs, and is used in terms of human inter-limb
      synergies. The developed control system provides assisted motion in coherence
      with the motion of other unassisted limbs. The system utilizes the instrumented
      cane together with body worn sensors, and provides assistance for start, stop and
      continuous walking. We verified the function of the proposed method and the
      developed wearable system through gait trials on treadmill and on ground. The
      achievement contributes to finding an intuitive and feasible interface between
      human and robot through wearable gait sensors for practical use of assistive
      technology. It also contributes to the technology for cognitively assisted
      locomotion, which helps the locomotion of physically challenged people. 

PMID- 24445418
TI  - Actomyosin contractility rotates the cell nucleus.
AB  - The cell nucleus functions amidst active cytoskeletal filaments, but its response
      to their contractile stresses is largely unexplored. We study the dynamics of the
      nuclei of single fibroblasts, with cell migration suppressed by plating onto
      micro-fabricated patterns. We find the nucleus undergoes noisy but coherent
      rotational motion. We account for this observation through a hydrodynamic
      approach, treating the nucleus as a highly viscous inclusion residing in a less
      viscous fluid of orientable filaments endowed with active stresses. Lowering
      actin contractility selectively by introducing blebbistatin at low concentrations
      drastically reduced the speed and coherence of the angular motion of the nucleus.
      Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the
      nucleus, with profile and magnitude consistent with the results of our
      theoretical approach. Coherent intracellular flows and consequent nuclear
      rotation thus appear to be an intrinsic property of cells. 

PMID- 24445419
TI  - Identification of QTL affecting resistance/susceptibility to acute Actinobacillus
      pleuropneumoniae infection in swine.
AB  - Actinobacillus pleuropneumoniae is among the most important pathogens worldwide
      in pig production. The agent can cause severe economic losses due to decreased
      performance, acute or chronic pleuropneumonia and an increased incidence of
      death. Therapeutics cannot be used in a sustainable manner, and vaccination is
      not always available, but discovering more about host defence and disease
      mechanisms might lead to new methods of prophylaxis. The aim of the present study
      was to detect quantitative trait loci (QTL) associated with
      resistance/susceptibility to A. pleuropneumoniae. Under controlled conditions,
      170 F2 animals of a Hampshire/Landrace family, with known differences in founder
      populations regarding A. pleuropneumoniae resistance, were challenged with an A.
      pleuropneumoniae serotype 7 aerosol followed by a detailed clinical,
      radiographic, ultrasonographic, pathological and bacteriological examination. F2
      pigs were genotyped with 159 microsatellite markers. Significant QTL were
      identified on Sus scrofa chromosomes (SSC) 2, 6, 12, 13, 16, 17 and 18. They
      explained 6-22% of phenotypic variance. One QTL on SSC2 reached significance on a
      genome-wide level for five associated phenotypic traits. A multiple regression
      analysis revealed a combinatory effect of markers SWR345 (SSC2) and S0143 (SSC12)
      on Respiratory Health Score, Clinical Score and the occurrence of death. The
      results indicate the genetic background of A. pleuropneumoniae resistance in
      swine and provide new insights into the genetic architecture of
      resistance/susceptibility to porcine pleuropneumonia. The results will be helpful
      in identifying the underlying genes and mechanisms.

PMID- 24445420
TI  - A genetic map of Peromyscus with chromosomal assignment of linkage groups (a
      Peromyscus genetic map).
AB  - The rodent genus Peromyscus is the most numerous and species-rich mammalian group
      in North America. The naturally occurring diversity within this genus allows
      opportunities to investigate the genetic basis of adaptation, monogamy,
      behavioral and physiological phenotypes, growth control, genomic imprinting, and
      disease processes. Increased genomic resources including a high quality genetic
      map are needed to capitalize on these opportunities. We produced interspecific
      hybrids between the prairie deer mouse (P. maniculatus bairdii) and the oldfield
      mouse (P. polionotus) and scored meiotic recombination events in backcross
      progeny. A genetic map was constructed by genotyping of backcross progeny at 185
      gene-based and 155 microsatellite markers representing all autosomes and the X
      chromosome. Comparison of the constructed genetic map with the molecular maps of
      Mus and Rattus and consideration of previous results from interspecific
      reciprocal whole chromosome painting allowed most linkage groups to be
      unambiguously assigned to specific Peromyscus chromosomes. Based on genomic
      comparisons, this Peromyscus genetic map covers ~83% of the Rattus genome and 79%
      of the Mus genome. This map supports previous results that the Peromyscus genome
      is more similar to Rattus than Mus. For example, coverage of the 20 Rattus
      autosomes and the X-chromosome is accomplished with only 28 segments of the
      Peromyscus map, but coverage of the 19 Mus autosomes and the X-chromosome
      requires 40 chromosomal segments of the Peromyscus map. Furthermore, a single
      Peromyscus linkage group corresponds to about 91% of the rat and only 76% of the
      mouse X-chromosomes.

PMID- 24445421
TI  - Heritability and coefficient of genetic variation analyses of phenotypic traits
      provide strong basis for high-resolution QTL mapping in the Collaborative Cross
      mouse genetic reference population.
AB  - Most biological traits of human importance are complex in nature; their
      manifestation controlled by the cumulative effect of many genetic factors
      interacting with one another and with the individual's life history. Because of
      this, mouse genetic reference populations (GRPs) consisting of collections of
      inbred lines or recombinant inbred lines (RIL) derived from crosses between
      inbred lines are of particular value in analysis of complex traits, since massive
      amounts of data can be accumulated on the individual lines. However, existing
      mouse GRPs are derived from inbred lines that share a common history, resulting
      in limited genetic diversity, and reduced mapping precision due to long-range
      gametic disequilibrium. To overcome these limitations, the Collaborative Cross
      (CC) a genetically highly diverse collection of mouse RIL was established. The
      CC, now in advanced stages of development, will eventually consist of about 500
      RIL derived from reciprocal crosses of eight divergent founder strains of mice,
      including three wild subspecies. Previous studies have shown that the CC indeed
      contains enormous diversity at the DNA level, that founder haplotypes are
      inherited in expected frequency, and that long-range gametic disequilibrium is
      not present. We here present data, primarily from our own laboratory, documenting
      extensive genetic variation among CC lines as expressed in broad-sense
      heritability (H(2)) and by the well-known "coefficient of genetic variation,"
      demonstrating the ability of the CC resource to provide unprecedented mapping
      precision leading to identification of strong candidate genes. 

PMID- 24445422
TI  - Structure and kinetics of chemically cross-linked protein gels from small-angle X
      ray scattering.
AB  - Glutaraldehyde (GA) reacts with amino groups in proteins, forming intermolecular
      cross-links that, at sufficiently high protein concentration, can transform a
      protein solution into a gel. Although GA has been used as a cross-linking reagent
      for decades, neither the cross-linking chemistry nor the microstructure of the
      resulting protein gel have been clearly established. Here we use small-angle X
      ray scattering (SAXS) to characterise the microstructure and structural kinetics
      of gels formed by cross-linking of pancreatic trypsin inhibitor, myoglobin or
      intestinal fatty acid-binding protein. By comparing the scattering from gels and
      dilute solutions, we extract the structure factor and the pair correlation
      function of the gels. The protein gels are spatially heterogeneous, with dense
      clusters linked by sparse networks. Within the clusters, adjacent protein
      molecules are almost in contact, but the protein concentration in the cluster is
      much lower than in a crystal. At the ~1 nm SAXS resolution, the native protein
      structure is unaffected by cross-linking. The cluster radius is in the range 10
      50 nm, with the cluster size determined mainly by the availability of lysine
      amino groups on the protein surface. The development of structure in the gel, on
      time scales from minutes to hours, appears to obey first-order kinetics. Cross
      linking is slower at acidic pH, where the population of amino groups in the
      reactive deprotonated form is low. These results support the use of cross-linked
      protein gels in NMR studies of protein dynamics and for modeling NMR relaxation
      in biological tissue. 

PMID- 24445423
TI  - A new colorimetric strategy for monitoring caspase 3 activity by HRP-mimicking
      DNAzyme-peptide conjugates.
AB  - A new method for caspase 3 activity assay has been developed based on HRP
      mimicking DNAzyme-peptide conjugates. The mechanism of detection was based on the
      specific cleavage of DEVD-peptides by active caspase 3 for recognition and the
      catalytic properties of HRP-mimicking DNAzymes for signal amplification. Under
      optimal conditions, the detection limit of caspase 3 was 0.89 nM. The proposed
      method was also successfully applied for the detection of caspase 3 in apoptosis
      cell lysates. 

PMID- 24445424
TI  - Phosphate management in chronic kidney disease.
AB  - PURPOSE OF REVIEW: The review focuses on the rationale and evidence behind
      management strategies for hyperphosphatemia in patients with chronic kidney
      disease (CKD). RECENT FINDINGS: Optimal management of phosphate in CKD remains an
      area of uncertainty, but multiple studies now point to a clinical benefit from
      the use of phosphate binders. Evidence of improved survival is particularly
      strong with sevelamer, though it remains unclear whether the absence of calcium
      or other properties of sevelamer are responsible for this relationship. Newer
      agents, such as iron-based binders or niacin compounds to inhibit phosphorus
      absorption, may have additional benefits which will be better defined with
      additional experience. A reduced pill count may be a particularly beneficial
      characteristic of newer agents, and has been associated with improved response to
      therapy. Increased use of frequent, nocturnal hemodialysis is an additional tool
      to help ameliorate phosphate control. Data on the reduction of fibroblast growth
      factor 23 through use of phosphate binders remain weak. SUMMARY: An improved
      understanding of phosphate regulation and the development of new therapeutic
      agents have reinvigorated a once stagnant field, but significant changes to
      practice cannot yet be justified. There is increasing support for using sevelamer
      in place of calcium-based binders, though economic practicability remains
      challenging.

PMID- 24445425
TI  - False elevation of bispectral index with a mandibular position in a patient
      undergoing craniotomy.

PMID- 24445426
TI  - Antagonistic interaction of selenomethionine enantiomers on methylmercury
      toxicity in the microalgae Chlorella sorokiniana.
AB  - The protective effect of selenium against mercury toxicity is well known
      especially between selenomethionine and methylmercury and it has been studied in
      several living organisms, however information is lacking about the interaction of
      these species in Chlorella. Investigation into which chiral form of
      selenomethionine effectively acts against the toxic effects of methylmercury has
      not previously been carried out. In the present work, two control cultures and
      two cultures of C. sorokiniana were grown in standard medium with D,L-SeMet, L
      SeMet or D-SeMet. After the experiment was started up MeHg(+) was added
      periodically to the cultures containing D,L-SeMet, L-SeMet, D-SeMet and to one of
      the control batches. The results show that both SeMet enantiomers counteract the
      toxicity of MeHg(+), by markedly increasing the total content of chlorophyll,
      carotenoids, as well as the dry weight and light dependent oxygen production,
      compared to the culture which is non pre-treated with SeMet and is only exposed
      to MeHg(+). The levels of MeHg(+) measured in cells are lower in the cultures pre
      treated with SeMet indicating that the passage of MeHg(+) into the cells is
      negligible when carried out in the presence of SeMet, or that SeMet enhances the
      release of MeHg(+). On the other hand, L-SeMet is directly involved in the
      detoxification of MeHg(+), but the involvement of D-SeMet occurs only indirectly
      since it has been neither identified in the medium nor in C. sorokiniana after
      supplementation with this enantiomer. It may be that D-SeMet is transformed into
      SeMeSec and L-SeMet. Moreover, SeMeSec is almost totally released from the cells
      after 72 hours. No mercury-selenium complex was detected but, since the summation
      of the different species identified accounted only for 77% of the total selenium
      and mercury measured directly after sample digestion, it is possible that they
      are present in the form of an undetected Se-Hg complex. This hypothesis is
      supported by the decrease of inorganic selenium during the experiment. The
      present paper reports new data about the relationship between the mechanism of
      detoxification of methylmercury and selenomethionine enantiomers through the
      study of the metabolic intermediates by means of speciation analysis.

PMID- 24445427
TI  - Planar hexagonal B(36) as a potential basis for extended single-atom layer boron
      sheets.
AB  - Boron is carbon's neighbour in the periodic table and has similar valence
      orbitals. However, boron cannot form graphene-like structures with a honeycomb
      hexagonal framework because of its electron deficiency. Computational studies
      suggest that extended boron sheets with partially filled hexagonal holes are
      stable; however, there has been no experimental evidence for such atom-thin boron
      nanostructures. Here, we show experimentally and theoretically that B36 is a
      highly stable quasiplanar boron cluster with a central hexagonal hole, providing
      the first experimental evidence that single-atom layer boron sheets with
      hexagonal vacancies are potentially viable. Photoelectron spectroscopy of B36(-)
      reveals a relatively simple spectrum, suggesting a symmetric cluster. Global
      minimum searches for B36(-) lead to a quasiplanar structure with a central
      hexagonal hole. Neutral B36 is the smallest boron cluster to have sixfold
      symmetry and a perfect hexagonal vacancy, and it can be viewed as a potential
      basis for extended two-dimensional boron sheets. 

PMID- 24445428
TI  - Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition
      of prion protein.
AB  - IMPORTANCE: Human transmission of bovine spongiform encephalopathy causes the
      fatal neurodegenerative condition variant Creutzfeldt-Jakob disease (vCJD) and,
      based on recent human prevalence studies, significant subclinical prion infection
      of the UK population. To date, all clinical cases have been fatal, totaling 228
      mostly young adults residing in the United Kingdom. OBSERVATIONS: Here we
      describe the investigation and case history of a patient recently diagnosed as
      having vCJD in the United Kingdom. Although his presentation, imaging findings,
      cerebrospinal fluid investigation results, and clinical progression were typical
      of other cases, tonsillar biopsy and subsequent examination of multiple tissues
      at autopsy showed minimal deposition of disease-associated prion protein in
      peripheral lymphoreticular tissue. The result of a blood test for vCJD, the
      Direct Detection Assay for vCJD, was negative. CONCLUSIONS AND RELEVANCE: These
      findings suggest that some patients with vCJD have very low peripheral prion
      colonization and therefore may not have detectable prion deposition in diagnostic
      tonsillar biopsy or markers of prion infection in blood. These results have
      implications for accurate interpretation of diagnostic tests and prevalence
      studies based on lymphoreticular tissue or blood.

PMID- 24445429
TI  - [From pediatricians to urologists: the consultation hour for adolescent males:
      urological care in puberty].
AB  - In order to adequately serve adolescent males concerning educational and
      informational needs and in order to compensate for the lack of male role models
      who are able to answer questions adolescents may have concerning physical
      maturation, sexual development and orientation accompanied by possible inner
      conflicts, it is recommended that the urologist establish a "consultation for
      young men" as a form of medical guidance during this difficult phase of life. 

PMID- 24445430
TI  - Chronic cortical and electromyographic recordings from a fully implantable
      device: preclinical experience in a nonhuman primate.
AB  - OBJECTIVE: Analysis of intra- and perioperatively recorded cortical and basal
      ganglia local field potentials in human movement disorders has provided great
      insight into the pathophysiology of diseases such as Parkinson's, dystonia, and
      essential tremor. However, in order to better understand the network
      abnormalities and effects of chronic therapeutic stimulation in these disorders,
      long-term recording from a fully implantable data collection system is needed.
      APPROACH: A fully implantable investigational data collection system, the
      Activa(r) PC + S neurostimulator (Medtronic, Inc., Minneapolis, MN), has been
      developed for human use. Here, we tested its utility for extended intracranial
      recording in the motor system of a nonhuman primate. The system was attached to
      two quadripolar paddle arrays: one covering sensorimotor cortex, and one covering
      a proximal forelimb muscle, to study simultaneous cortical field potentials and
      electromyography during spontaneous transitions from rest to movement. MAIN
      RESULTS: Over 24 months of recording, movement-related changes in physiologically
      relevant frequency bands were readily detected, including beta and gamma signals
      at approximately 2.5 MUV/[Formula: see text] and 0.7 MUV/[Formula: see text],
      respectively. The system architecture allowed for flexible recording
      configurations and algorithm triggered data recording. In the course of
      physiological analyses, sensing artifacts were observed (~1 MUVrms stationary
      tones at fixed frequency), which were mitigated either with post-processing or
      algorithm design and did not impact the scientific conclusions. Histological
      examination revealed no underlying tissue damage; however, a fibrous capsule had
      developed around the paddles, demonstrating a potential mechanism for the
      observed signal amplitude reduction. SIGNIFICANCE: This study establishes the
      usefulness of this system in measuring chronic brain and muscle signals. Use of
      this system may potentially be valuable in human trials of chronic brain
      recording in movement disorders, a next step in the design of closed-loop
      neurostimulation paradigms.

PMID- 24445431
TI  - Understanding and controlling plasmon-induced convection.
AB  - The heat generation and fluid convection induced by plasmonic nanostructures is
      attractive for optofluidic applications. However, previously published
      theoretical studies predict only nanometre per second fluid velocities that are
      inadequate for microscale mass transport. Here we show both theoretically and
      experimentally that an array of plasmonic nanoantennas coupled to an optically
      absorptive indium-tin-oxide (ITO) substrate can generate >micrometre per second
      fluid convection. Crucially, the ITO distributes thermal energy created by the
      nanoantennas generating an order of magnitude increase in convection velocities
      compared with nanoantennas on a SiO2 base layer. In addition, the plasmonic array
      alters absorption in the ITO, causing a deviation from Beer-Lambert absorption
      that results in an optimum ITO thickness for a given system. This work elucidates
      the role of convection in plasmonic optical trapping and particle assembly, and
      opens up new avenues for controlling fluid and mass transport on the micro- and
      nanoscale. 

PMID- 24445432
TI  - Renal artery stenosis in children: therapeutic percutaneous balloon and stent
      angioplasty.
AB  - BACKGROUND: Renal artery stenosis (RAS) accounts for 10 % of cases of systemic
      hypertension in children. Initial management involves anti-hypertensive therapy.
      Percutaneous interventions are documented for the treatment of RAS in the adult
      population. In children, case reports suggest benefit. METHODS: This is a
      retrospective analysis of consecutive patients referred for catheterization for
      RAS between 2002 and 2010 at a single institution. Recorded variables included:
      age, weight, systemic blood pressure, minimal luminal diameter, interventional
      devices, antihypertensive medications, contrast volume, and complications.
      RESULTS: Twelve patients (median age 8.2, IQR 6-12.4 years); median weight 42.8
      kg, IQR: 25-47.4 kg) were referred for renal artery catheterization and underwent
      percutaneous intervention. Overall, minimal luminal diameter (MLD) increased by
      1.2 +/- 0.9 mm for all patients (p < 0.05) and by 1.3 +/- 0.9 mm for post-renal
      transplant patients (p < 0.05). Only stent angioplasty patients demonstrated
      significant improved blood pressure (p < 0.05). One patient had stent thrombosis
      requiring re-intervention with repeat balloon angioplasty. CONCLUSIONS: This
      retrospective analysis suggests that percutaneous intervention might play a role
      in the management of RAS, with an improvement in MLD in children with RAS.
      Transcatheter intervention is technically feasible with low morbidity. A
      prospective, longitudinal study is warranted to compare standard medical therapy
      with percutaneous interventions.

PMID- 24445433
TI  - Coordination of kidney organogenesis by Wnt signaling.
AB  - Several Wnt proteins are expressed in the embryonic kidney during various stages
      of development. Gene knockout models and ex vivo studies have provided strong
      evidence that Wnt-mediated signals are essential in renal ontogeny. Perhaps the
      most critical factors, Wnt9b and Wnt4, function during the early phase when the
      cap mesenchyme is induced to undergo morphogenesis into a nephron. Wnt11 controls
      early ureteric bud branching and contributes to the final kidney size. In
      addition to its inductive role, later on Wnt9b plays a significant role in the
      convergent extension of the tubular epithelial cells, while Wnt4 signaling
      controls smooth muscle cell fates in the medulla. Wnt7b has a specific function
      together with its likely antagonist Dkk1 in controlling the morphogenesis of the
      renal medulla. The signal-transduction mechanisms of the Wnts in kidney ontogeny
      have not been resolved, but studies characterizing the downstream signaling
      pathways are emerging. Aberrant Wnt signaling may lead to kidney diseases ranging
      from fatal kidney agenesis to more benign phenotypes. Wnt-mediated signaling
      regulates several critical aspects of kidney development from the early inductive
      stages to later steps of tubular epithelial maturation. 

PMID- 24445434
TI  - Evaluation of the microleakage of different class V cavities prepared by using
      Er:YAG laser, ultrasonic device, and conventional rotary instruments with two
      dentin bonding systems (an in vitro study).
AB  - This study aimed to evaluate the extent of microleakage in class V cavities
      prepared with bur, Er:YAG laser, and ultrasonic, hybridized with two different
      bonding agents ("Single bonding" solvent-free bonding agent and "Swiss TEC SL
      bond" alcohol-based solvent). Thirty freshly extracted human premolars were
      divided into three groups (n = 10), on each tooth, two cavities were prepared on
      the buccal and the lingual surfaces, and each group was subdivided into two
      subgroups (n = 5). Group 1: 20 cavities were prepared by using Er:YAG laser (500
      mJ, 10 Hz, 63.69 J/cm(2)) (subgroup1a: Single bonding was used with 10 cavities;
      subgroup 1b: Swiss TEC SL bond was used with 10 cavities). Group 2: 20 cavities
      were prepared by using ultrasonic (subgroup 2a: Single bonding was used with 10
      cavities; subgroup 2b: Swiss TEC SL bond was used with 10 cavities). Group 3: 20
      cavities were prepared by using burs (subgroup 3a: Single bonding was used with
      10 cavities; subgroup 3b: Swiss TEC SL bond was used with 10 cavities). Cavities
      were restored with a micro-hybrid composite resin. After thermocycling, the
      specimens were immersed in 2 % methylene blue solution for 4 h and then sectioned
      in the bucco-lingual direction. Dye penetration was scored based upon the extent
      of the dye using a stereomicroscope. The two-way ANOVA test and paired t-test
      revealed no statistically significant differences among the methods of
      preparation (conventional, laser, and ultrasonic). However, statistical
      differences were found between the adhesives tested: the "Single bonding", which
      represented the solvent-free bonding agent, had lower microleakage values than
      "Swiss TEC SL bond", which represented the alcohol-based bonding agent. Based on
      the results of this study, it can be concluded that the Erbium:Yttrium-Aluminum
      Garnet (Er:YAG) laser and ultrasonic are as effective as the conventional method
      for preparing cavities and the extent of microleakage depends on the type of the
      bonding agents.

PMID- 24445435
TI  - Evaluation of the antipsychotic potential of aqueous fraction of Securinega
      virosa root bark extract in mice.
AB  - Securinega virosa (Roxb ex. Willd) Baill. is a plant which is commonly used in
      African traditional medicine in management of mental illness. Previous study
      showed that the crude methanolic root bark extract of the plant possesses
      antipsychotic activity. In this study, the antipsychotic potential of the
      residual aqueous fraction of the plant was evaluated using two experimental
      models, apomorphine induced stereotypic climbing behaviour and swim induced
      grooming, all in mice. The effect of the fraction on haloperidol-induced
      catalepsy was also evaluated. The fraction significantly reduced the mean
      climbing score at the highest dose tested (500 mg/kg). In the swim-induced
      grooming test, the fraction significantly and dose-dependently (125-500 mg/kg)
      decreased the mean number and mean duration of swim-induced grooming activity in
      mice. Similarly, the standard haloperidol (1 mg/kg) significantly (p < 0.001)
      decreased the mean grooming episodes and duration. However, the fraction did not
      significantly potentiate haloperidol-induced catalepsy. These results suggest
      that the residual aqueous fraction of methanol root bark extract of Securinega
      virosa contains biological active principle with antipsychotic potential.

PMID- 24445436
TI  - Leaning in and holding on: team support with unexpected death.
AB  - Integral to the care of medically fragile infants and children is the sobering
      reality that not all will survive. Supporting children and families through the
      dying process requires knowledge, skill, compassion, and a willingness to be
      present to the suffering of others. As healthcare professionals journey with a
      dying child, they experience an ongoing dual nature of their own grief, shifting
      between focusing on the loss at hand or avoiding the loss and refocusing their
      attention elsewhere. This internal conflict may be potentiated with the sudden,
      unexpected death of a patient, which affords little time for caregivers to
      process their own experience of the loss. When an unanticipated death occurs, a
      palpable grief ripples through the entire unit, impacting caregivers, the
      bereaved parents, and other patients and families. Such an event holds the
      potential for either team disorganization or growth. This article presents a case
      study of one unit's response to the unexpected death of a long-term patient,
      which caused caregivers to lean in to support each other. Using a case study
      approach, the author identifies strategies to best guide teams when death arrives
      without warning, and provides ideas for cocreating ritual to honor relationship
      in the midst of tragedy.

PMID- 24445437
TI  - The free energy landscape in translational science: how can somatic mutations
      result in constitutive oncogenic activation?
AB  - The free energy landscape theory has transformed the field of protein folding.
      The significance of perceiving function in terms of conformational heterogeneity
      is gradually shifting the interest in the community from folding to function.
      From the free energy landscape standpoint the principles are unchanged: rather
      than considering the entire protein conformational landscape, the focus is on the
      ensemble around the bottom of the folding funnel. The protein can be viewed as
      populating one of two states: active or inactive. The basins of the two states
      are separated by a surmountable barrier, which allows the conformations to switch
      between the states. Unless the protein is a repressor, under physiological
      conditions it typically populates the inactive state. Ligand binding (or post
      translational modification) triggers a switch to the active state. Constitutive
      allosteric mutations work by shifting the population from the inactive to the
      active state and keeping it there. This can happen by either destabilizing the
      inactive state, stabilizing the active state, or both. Identification of the
      mechanism through which they work is important since it may assist in drug
      discovery. Here we spotlight the usefulness of the free energy landscape in
      translational science, illustrating how oncogenic mutations can work in key
      proteins from the EGFR/Ras/Raf/Erk/Mek pathway, the main signaling pathway in
      cancer. Finally, we delineate the key components which are needed in order to
      trace the mechanism of allosteric events. 

PMID- 24445438
TI  - Novel hydrated graphene ribbon unexpectedly promotes aged seed germination and
      root differentiation.
AB  - It is well known that graphene (G) induces nanotoxicity towards living organisms.
      Here, a novel and biocompatible hydrated graphene ribbon (HGR) unexpectedly
      promoted aged (two years) seed germination. HGR formed at the normal temperature
      and pressure (120 days hydration), presented 17.1% oxygen, 0.9% nitrogen groups,
      disorder-layer structure, with 0.38 nm thickness ribbon morphology.
      Interestingly, there were bulges around the edges of HGR. Compared to G and
      graphene oxide (GO), HGR increased seed germination by 15% root differentiation
      between 52 and 59% and enhanced resistance to oxidative stress. The metabonomics
      analysis discovered that HGR upregulated carbohydrate, amino acid, and fatty
      acids metabolism that determined secondary metabolism, nitrogen sequestration,
      cell membrane integrity, permeability, and oxidation resistance. Hexadecanoic
      acid as a biomarker promoted root differentiation and increased the germination
      rate. Our discovery is a novel HGR that promotes aged seed germination,
      illustrates metabolic specificity among graphene-based materials, and inspires
      innovative concepts in the regulation of seed development. 

PMID- 24445439
TI  - Reproduction and growth of the terebratulid brachiopod Liothyrella neozelanica
      Thomson, 1918 From Doubtful Sound, New Zealand.
AB  - The reproductive cycle and growth of the temperate New Zealand rhynchonelliform
      brachiopod Liothyrella neozelanica was examined over 12 months (December 2010 and
      December 2011). The research aimed to clarify the spawning cycle, life history,
      population size, and age structure of L. neozelanica and to enable more direct
      comparisons with the Antarctic brachiopod Liothyrella uva. Reproduction over the
      course of a year was quantified by monthly examination of gonad size and
      gametogenesis. Histological examination indicated a seasonal cycle with
      prolonged, potentially asynchronous spawning. Increased numbers of large oocytes
      in July followed by a significant decrease in September suggest that female
      spawning takes place in early austral spring. A decrease in the proportion of the
      gonad area occupied by sperm during September suggests a level of spawning
      synchrony between sexes. Somatic growth was modeled from 60 tagged individuals. A
      maximum size of ~ 50-mm shell length is achieved at 17 years of age, and
      instantaneous growth is highest in juveniles (9.7 mm yr(-1)). Mortality rate was
      estimated from the age distribution at an instantaneous rate of 0.14 yr(-1). A
      left-skewed size-frequency distribution implies high mortality in juveniles. 

PMID- 24445440
TI  - Sublethal behavioral and physiological effects of the biomedical bleeding process
      on the American horseshoe crab, Limulus polyphemus.
AB  - The hemolymph of the American horseshoe crab, Limulus polyphemus, is harvested
      from over 500,000 animals annually to produce Limulus amebocyte lysate (LAL), a
      medically important product used to detect pathogenic bacteria. Declining
      abundance of spawning Limulus females in heavily harvested regions suggests
      deleterious effects of this activity, and while mortality rates of the harvest
      process are known to be 10%-30%, sublethal behavioral and physiological effects
      are not known. In this study, we determined the impact of the harvest process on
      locomotion and hemocyanin levels of 28 female horseshoe crabs. While mortality
      rates after bleeding (18%) were similar to previous studies, we found significant
      decreases in the linear and angular velocity of freely moving animals, as well as
      changes in their activity levels and expression of circatidal behavioral rhythms.
      Further, we found reductions in hemocyanin levels, which may alter immune
      function and cuticle integrity. These previously unrecognized behavioral and
      physiological deficits suggest that the harvest of LAL may decrease female
      fitness, and thus may contribute to the current population decline. 

PMID- 24445441
TI  - Ink from longfin inshore squid, Doryteuthis pealeii, as a chemical and visual
      defense against two predatory fishes, summer flounder, Paralichthys dentatus, and
      sea catfish, Ariopsis felis.
AB  - Chemical and visual defenses are used by many organisms to avoid being approached
      or eaten by predators. An example is inking molluscs-including gastropods such as
      sea hares and cephalopods such as squid, cuttlefish, and octopus-which release a
      colored ink upon approach or attack. Previous work showed that ink can protect
      molluscs through a combination of chemical, visual, and other effects. In this
      study, we examined the effects of ink from longfin inshore squid, Doryteuthis
      pealeii, on the behavior of two species of predatory fishes, summer flounder,
      Paralichthys dentatus, and sea catfish, Ariopsis felis. Using a cloud assay, we
      found that ink from longfin inshore squid affected the approach phase of
      predation by summer flounder, primarily through its visual effects. Using a food
      assay, we found that the ink affected the consummatory and ingestive phase of
      predation of both sea catfish and summer flounder, through the ink's chemical
      properties. Fractionation of ink showed that most of its deterrent chemical
      activity is associated with melanin granules, suggesting that either compounds
      adhering to these granules or melanin itself are the most biologically active.
      This work provides the basis for a comparative approach to identify deterrent
      molecules from inking cephalopods and to examine neural mechanisms whereby these
      chemicals affect behavior of fish, using the sea catfish as a chemosensory model.

PMID- 24445442
TI  - Defensive responses of cuttlefish to different teleost predators.
AB  - We evaluated cuttlefish (Sepia officinalis) responses to three teleost predators:
      bluefish (Pomatomus saltatrix), summer flounder (Paralichthys dentatus), and
      black seabass (Centropristis striata). We hypothesized that the distinct body
      shapes, swimming behaviors, and predation tactics exhibited by the three fishes
      would elicit markedly different antipredator responses by cuttlefish. Over the
      course of 25 predator-prey behavioral trials, 3 primary and 15 secondary defense
      behaviors of cuttlefish were shown to predators. In contrast, secondary defenses
      were not shown during control trials in which predators were absent. With seabass
      a benthic, sit-and-pursue predator-cuttlefish used flight and spent more time
      swimming in the water column than with other predators. With bluefish-an active,
      pelagic searching predator-cuttlefish remained closely associated with the
      substrate and relied more on cryptic behaviors. Startle (deimatic) displays were
      the most frequent secondary defense shown to seabass and bluefish, particularly
      the Dark eye ring and Deimatic spot displays. We were unable to evaluate
      secondary defenses by cuttlefish to flounder-a lie-and-wait predator-because
      flounder did not pursue cuttlefish or make attacks. Nonetheless, cuttlefish used
      primary defense during flounder trials, alternating between cryptic still and
      moving behaviors. Overall, our results suggest that cuttlefish may vary their
      behavior in the presence of different teleost predators: cryptic behaviors may be
      more important in the presence of active searching predators (e.g., bluefish),
      while conspicuous movements such as swimming in the water column and startle
      displays may be more prevalent with relatively sedentary, bottom-associated
      predators (e.g., seabass). 

PMID- 24445443
TI  - Shell hardness and compressive strength of the Eastern oyster, Crassostrea
      virginica, and the Asian oyster, Crassostrea ariakensis.
AB  - The valves of oysters act as a physical barrier between tissues and the external
      environment, thereby protecting the oyster from environmental stress and
      predation. To better understand differences in shell properties and predation
      susceptibilities of two physiologically and morphologically similar oysters,
      Crassostrea virginica and Crassostrea ariakensis, we quantified and compared two
      mechanical properties of shells: hardness (resistance to irreversible
      deformation; GPa) and compressive strength (force necessary to produce a crack;
      N). We found no differences in the hardness values between foliated layers
      (innermost and outermost foliated layers), age class (C. virginica: 1, 4, 6, 9
      years; C. ariakensis: 4, 6 years), or species. This suggests that the foliated
      layers have similar properties and are likely composed of the same material. The
      compressive force required to break wet and dry shells was also not different.
      However, the shells of both six- and nine-year-old C. virginica withstood higher
      compressive force than C. virginica shells aged either one or four, and the
      shells of C. ariakensis at both ages studied (4- and 6-years-old). Differences in
      ability to withstand compressive force are likely explained by differences in
      thickness and density between age classes and species. Further, we compared the
      compressive strength of differing ages of these two species to the crushing force
      of common oyster predators in the Chesapeake Bay. By studying the physical
      properties of shells, this work may contribute to a better understanding of the
      mechanical defenses of oysters as well as of their predation vulnerabilities. 

PMID- 24445444
TI  - Sole smooth muscle states determine gliding rate in the freshwater snail Lymnaea
      stagnalis.
AB  - The sole of crawling gastropods is a unique model for studying the function of
      smooth muscles and ciliated epithelium. The gastropod snail Lymnaea stagnalis
      glides over the substratum without visible muscular contraction in its sole;
      consequently, the gliding was thought to be due to sole cilia. However, we have
      shown that the sole muscles in Lymnaea are phasic smooth muscles. They contribute
      extensively to gliding rate, which is directly correlated with the sole length
      (longitudinal sole muscle tonus) that varies widely during gliding. Here, we show
      that the linear relationship between gliding rate and sole length in Lymnaea may
      be modified. Serotonin increases gliding rate and has no effect on sole length.
      Dopamine contracts the sole and, consequently, slows the gliding rate, while
      ergometrine (a blocker of dopamine receptors) relaxes the sole and increases
      gliding rate. These influences on locomotion rate and sole length are similar to
      those obtained earlier for Helix lucorum, in which the substances changed the
      number and contraction force of muscle cells involved in peristaltic locomotory
      waves. Taken together, the data obtained here for Lymnaea and earlier for Helix
      describe the fundamental mechanisms for controlling phasic smooth muscles. 

PMID- 24445445
TI  - Hemichordate molecular phylogeny reveals a novel cold-water clade of harrimaniid
      acorn worms.
AB  - Hemichordates are instrumental to understanding early deuterostome and chordate
      evolution, yet diversity and relationships within the group have been
      understudied. Recently, there has been renewed interest in hemichordate diversity
      and taxonomy, although current findings suggest that much hemichordate diversity
      remains to be discovered. Herein, we present a molecular phylogenetic study based
      on nuclear 18S rDNA sequence data, which includes 35 previously unsampled taxa
      and represents all recognized hemichordate families. We include mitochondrial 16S
      rDNA data from 66 enteropneust taxa and three pterobranch Rhabdopleura species,
      and recover colonial pterobranchs and solitary enteropneusts as reciprocally
      monophyletic taxa. Our phylogenetic results also reveal a previously unknown
      clade of at least four species of harrimaniid enteropneusts from cold waters,
      including Antarctica, the North Atlantic around Iceland and Norway, and the deep
      sea off Oregon. These small worms (1-5 mm in length), occur from 130 to 2950 m
      and are not closely related to other deep-sea harrimaniids, indicating that
      diversity of enteropneusts within the deep sea is broader than previously
      described in the literature. Discovery of this clade, as well as larger
      torquaratorids from Antarctica, strengthens hypotheses of close associations
      between Antarctic and deep-sea fauna. 

PMID- 24445447
TI  - Location, extent, and multifocality of positive surgical margins for biochemical
      recurrence prediction after radical prostatectomy.
AB  - PURPOSE: To study the prognostic value of extent, number, and location of
      positive surgical margins (PSM). METHODS: A total of 1,504 consecutive adjuvant
      treatment naive and node-negative radical prostatectomy men were included in a
      prospective database including extent, number, and location of PSM. Mean follow
      up was 33 months. Endpoint was biochemical progression-free (bPFS) survival. The
      impact of margin status and characteristics was assessed in time-dependent
      analyses using Cox regression and Kaplan-Meier methods. RESULTS: PSM was reported
      in 26.7 % of patients. The predominant PSM locations were apex and posterior
      locations. Median PSM length was 4.0 mm. The 2-year bPFS was 73.7 % in PSM
      patients as compared to 93.0 % in NSM patients (p < 0.001). The rate and extent
      of PSM increased significantly with pathologic stage (p < 0.001). The extent of
      PSM length was linearly correlated with bPFS (p = 0.017, coefficient: -0.122). In
      univariable analysis, extent and number of PSM were significantly linked to
      outcomes. None of PSM subclassifications significantly influenced the bPFS rates
      in the subgroup of pT2 disease patients. Conversely, stratification by PSM
      location (apex vs. other locations, p = 0.008), by PSM number (p = 0.006), and by
      PSM length (p < 0.001) showed significant differences in pT3-4 cancer patients.
      In that subgroup, PSM length also added to bPFS prediction using PSM status only
      in multivariable models (p = 0.005). CONCLUSIONS: PSM subclassifications do not
      improve the biochemical recurrence prediction in organ-confined disease. In non
      organ-confined disease, PSM length (>=3 mm), multifocality (>=3 sites), and
      apical location are significantly linked to poorer outcomes and could justify a
      more aggressive adjuvant treatment approach.

PMID- 24445448
TI  - Neuromuscular activity of Micrurus laticollaris (Squamata: Elapidae) venom in
      vitro.
AB  - In this work, we have examined the neuromuscular activity of Micrurus
      laticollaris (Mexican coral snake) venom (MLV) in vertebrate isolated nerve
      muscle preparations. In chick biventer cervicis preparations, the MLV induced an
      irreversible concentration- and time-dependent (1-30 ug/mL) neuromuscular
      blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures
      evoked by exogenous acetylcholine were completely abolished by MLV, whereas those
      of KCl were also significantly altered (86% +/- 11%, 53% +/- 11%, 89% +/- 5% and
      89% +/- 7% for one, three, 10 and 30 ug of venom/mL, respectively; n = 4; p <
      0.05). In mouse phrenic nerve-diaphragm preparations, MLV (1-10 ug/mL) promoted a
      slight increase in the amplitude of twitch-tension (3 ug/mL), followed by
      neuromuscular blockade (n = 4); the highest concentration caused complete
      inhibition of the twitches (time for 50% blockade = 26 +/- 3 min), without
      exhibiting a previous neuromuscular facilitation. The venom (3 ug/mL) induced a
      biphasic modulation in the frequency of miniature end-plate potentials
      (MEPPs)/min, causing a significant increase after 15 min, followed by a decrease
      after 60 min (from 17 +/- 1.4 (basal) to 28 +/- 2.5 (t15) and 12 +/- 2 (t60)).
      The membrane resting potential of mouse diaphragm preparations pre-exposed or not
      to d-tubocurarine (5 ug/mL) was also significantly less negative with MLV (10
      ug/mL). Together, these results indicate that M. laticollaris venom induces
      neuromuscular blockade by a combination of pre- and post-synaptic activities. 

PMID- 24445451
TI  - Abstracts from the Cardiovascular Research: Bench to Bedside and Back Again. A
      40th Anniversary Celebration of the BSCR. September 9-10, 2013, London, UK.

PMID- 24445449
TI  - Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase
      susceptibility to Clostridium difficile infection.
AB  - Antibiotics can have significant and long-lasting effects on the gastrointestinal
      tract microbiota, reducing colonization resistance against pathogens including
      Clostridium difficile. Here we show that antibiotic treatment induces substantial
      changes in the gut microbial community and in the metabolome of mice susceptible
      to C. difficile infection. Levels of secondary bile acids, glucose, free fatty
      acids and dipeptides decrease, whereas those of primary bile acids and sugar
      alcohols increase, reflecting the modified metabolic activity of the altered gut
      microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can
      exploit specific metabolites that become more abundant in the mouse gut after
      antibiotics, including the primary bile acid taurocholate for germination, and
      carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for
      growth. Our results indicate that antibiotic-mediated alteration of the gut
      microbiome converts the global metabolic profile to one that favours C. difficile
      germination and growth. 

PMID- 24445477
TI  - Mechanisms of autoimmunity in human diseases: a critical review of current dogma.
AB  - PURPOSE OF REVIEW: Autoimmune diseases such as rheumatoid arthritis (RA) pose an
      increasing, worldwide economic and health burden. Significantly, no cure exists
      for the majority of autoimmune diseases and consequently treatment is largely
      aimed at controlling disease symptoms. Therefore, there exists a critical need to
      develop new approaches that directly address the cause of disease, leading to
      disease remission and ultimately cure. RECENT FINDINGS: The organs, cells and
      molecules involved in the breach of self-tolerance have been partially defined in
      experimental models of autoimmunity. However, the broad applicability of this
      dogma in clinical disease is only partially understood. This gap between analyses
      of established disease and investigating early disease pathogenesis argues for
      the need for complementary studies in mice and humans. SUMMARY: Through a
      combination of clinical and experimental systems, novel autoantigens and
      neoepitopes involved in RA have been revealed. These have clear utility in
      predisease diagnosis and offer the possibility of antigen-specific immunotherapy.
      Ongoing experimental and clinical studies, for example using dendritic cell
      transfer, will facilitate a clearer understanding of the molecules, cells and
      organs that should be targeted to reinstate immunological tolerance. Antigen
      specific immunotherapy therefore offers disease intervention without broad
      immunosuppression, and most importantly increases the likelihood of achieving
      true disease remission and cure.

PMID- 24445478
TI  - T cell subsets and their role in the pathogenesis of rheumatic disease.
AB  - PURPOSE OF REVIEW: T lymphocytes are critical to the pathogenesis of systemic
      rheumatic diseases. Understanding of the roles of T cells in disease has been
      enriched by the description of highly distinct effector subsets of CD4 T
      lymphocytes. The purpose of this review is to describe selected advances in the
      biology of T lymphocytes that are pertinent to the pathogenesis or treatment of
      rheumatic diseases. RECENT FINDINGS: Knowledge is expanding about not only
      pathogenic effector T cell subsets, such as the TH17 cells, but also of
      regulatory T cells (Treg), the functions of which are defective, but correctable,
      in several rheumatic diseases. Although the initial agent that demonstrated a
      role for T cells in rheumatoid arthritis was CTLA4-Ig (abatacept), use of this
      biologic is now expanding to other rheumatic diseases. Moreover, effects of other
      biologics are now understood to in part be mediated by effects on T cell subsets.
      Experimental model systems in rodents continue to be valuable testing grounds for
      future approaches to treatment of human disease. Meanwhile, the roles of effector
      T cell subsets are becoming clearer in conditions such as Sjogren's syndrome and
      scleroderma. Finally, rheumatic diseases, including rheumatoid arthritis and
      spondyloarthropathies, have been critical for identification of new innate-like T
      cell subsets. SUMMARY: Imbalances in the numbers and functions of specific T cell
      subsets are key pathogenic derangements in systemic rheumatic diseases, and these
      insights are leading to changes in clinical practice.

PMID- 24445480
TI  - Clinical research in rheumatology 2012-2013: methodologic considerations in study
      design.

PMID- 24445479
TI  - Uricosuric drugs: the once and future therapy for hyperuricemia?
AB  - PURPOSE OF REVIEW: Although uricosuric agents provide the most time-honoured
      approach to the control of hyperuricemia, their place in the armamentarium has
      been eclipsed by that of xanthine oxidase inhibitors. This review considers the
      potential for uricosuric agents from the perspective of recent progress in the
      understanding of urate transport systems. RECENT FINDINGS: No new agents have yet
      become available, but promising new drugs are under development. Better
      understanding of the transporters URAT1 and ABCG2 in particular would appear to
      provide opportunities for more selective, better tolerated agents to increase the
      renal clearance of uric acid and thereby control hyperuricemia. SUMMARY:
      Conceptually, modest inhibition of renal tubular reabsorption should provide
      effective relief for the millions of individuals who are now hyperuricemic and
      who suffer from its principal consequence, gout.

PMID- 24445481
TI  - Crystal deposition diseases.

PMID- 24445482
TI  - Optogenetic micro-electrocorticography for modulating and localizing cerebral
      cortex activity.
AB  - OBJECTIVE: Spatial localization of neural activity from within the brain with
      electrocorticography (ECoG) and electroencephalography remains a challenge in
      clinical and research settings, and while microfabricated ECoG (micro-ECoG) array
      technology continues to improve, complementary methods to simultaneously modulate
      cortical activity while recording are needed. APPROACH: We developed a neural
      interface utilizing optogenetics, cranial windowing, and micro-ECoG arrays
      fabricated on a transparent polymer. This approach enabled us to directly
      modulate neural activity at known locations around micro-ECoG arrays in mice
      expressing Channelrhodopsin-2. We applied photostimuli varying in time, space and
      frequency to the cortical surface, and we targeted multiple depths within the
      cortex using an optical fiber while recording micro-ECoG signals. MAIN RESULTS:
      Negative potentials of up to 1.5 mV were evoked by photostimuli applied to the
      entire cortical window, while focally applied photostimuli evoked spatially
      localized micro-ECoG potentials. Two simultaneously applied focal stimuli could
      be separated, depending on the distance between them. Photostimuli applied within
      the cortex with an optical fiber evoked more complex micro-ECoG potentials with
      multiple positive and negative peaks whose relative amplitudes depended on the
      depth of the fiber. SIGNIFICANCE: Optogenetic ECoG has potential applications in
      the study of epilepsy, cortical dynamics, and neuroprostheses.

PMID- 24445483
TI  - A practical guide to prevention for forensic nursing.
AB  - Interpersonal violence (IPV) is a pervasive issue across the United States,
      affecting one in five women and costing the nation up to $750 billion per year in
      additional healthcare spending. Prevention of IPV by forensic nurses may be an
      underrecognized and underutilized activity as forensic nursing emphasizes
      collection of evidence and provision of acute care to victims of violence. The
      "Upstream Adage" parable has been used to identify activities that can be applied
      to the care of victims. Forensic nurses can expand their practice activities into
      an "upstream" focus by targeting communities and individuals at different levels
      of risk and participating in key interventions before violence occurs. The role
      for forensic nurses to inform, participate, and implement primary, secondary, and
      tertiary prevention activities can have positive influences on the problem of IPV
      that extends well beyond the provision of direct care. 

PMID- 24445484
TI  - The impact of heat, cold, and heat waves on hospital admissions in eight cities
      in Korea.
AB  - Although the impact of temperature on mortality is well documented, relatively
      fewer studies have evaluated the associations of temperature with morbidity
      outcomes such as hospital admissions, and most studies were conducted in North
      America or Europe. We evaluated weather and hospital admissions including
      specific causes (allergic disease, asthma, selected respiratory disease, and
      cardiovascular disease) in eight major cities in Korea from 2003 to 2008. We also
      explored potential effect modification by individual characteristics such as sex
      and age. We used hierarchical modeling to first estimate city-specific
      associations between heat, cold, or heat waves and hospitalizations, and then
      estimated overall effects. Stratified analyses were performed by cause of
      hospitalization, sex, and age (0-14, 15-64, 65-74, and >=75 years).
      Cardiovascular hospitalizations were significantly associated with high
      temperature, whereas hospitalizations for allergic disease, asthma, and selected
      respiratory disease were significantly associated with low temperature. The
      overall heat effect for cardiovascular hospitalization was a 4.5% (95% confidence
      interval 0.7, 8.5%) increase in risk comparing hospitalizations at 25 to 15 
      degrees C. For cold effect, the overall increase in risk of hospitalizations
      comparing 2 with 15  degrees C was 50.5 (13.7, 99.2%), 43.6 (8.9, 89.5%), and
      53.6% (9.8, 114.9%) for allergic disease, asthma, and selected respiratory
      disease, respectively. We did not find statistically significant effects of heat
      waves compared with nonheat wave days. Our results suggest susceptible
      populations such as women and younger persons. Our findings provide suggestive
      evidence that both high and low ambient temperatures are associated with the risk
      of hospital admissions, particularly in women or younger person, in Korea.

PMID- 24445485
TI  - Phase I trials in patients with relapsed, advanced upper gastrointestinal
      carcinomas: experience in a specialist unit.
AB  - BACKGROUND: Conventional therapeutic options for patients with advanced upper
      gastrointestinal cancers (UGIC) are limited. Following first-line treatments,
      some patients are offered experimental therapies, including participation in
      Phase I trials. This study aims to describe the experience of UGIC patients
      treated in a dedicated Phase I unit. METHODS: Patient, tumour and treatment
      characteristics, and clinical outcomes of UGIC patients treated consecutively at
      the Drug Development Unit, Royal Marsden Hospital, between 2005 and 2009, were
      recorded. RESULTS: Ninety-six patients who previously received a median of 2
      (range 1-4) lines of chemotherapies were treated in 30 Phase I trials. Of 81
      evaluable patients, 9 achieved RECIST-objective response (11 %) with a 6-month
      clinical benefit rate of 14 %. Median progression free and overall survival were
      7.7 weeks [95 %CI 7.7 (6.4-9.0)] and 19.1 weeks (95 %CI 17.5-20.8), respectively.
      Grade 3 or 4 toxicities were observed in 37 patients (39 %) and led to trial
      discontinuation in 9 (9 %); no toxicity-related death was recorded. In the
      multivariate analysis, serum albumin (<35 g/dl, HR2.0, p = 0.002) and lactate
      dehydrogenase (>192 MUmol/l, HR1.7, p = 0.016) were prognostic of overall
      survival. CONCLUSION: Phase I clinical trials can be considered a reasonable
      option in selected patients with relapsed UGIC. The use of objective
      prognosticators may improve selection and risk/benefit profile of patients.

PMID- 24445486
TI  - New devices for TAVI: technologies and initial clinical experiences.
AB  - Treatment of aortic stenosis in high-risk surgical patients has been modified in
      the past 10 years owing to the introduction of transcatheter aortic valve
      implantation (TAVI). Several issues affecting outcomes with implantation of the
      first-generation TAVI devices remain unresolved, including haemorrhagic and
      vascular complications, neurological events, rhythm disturbances, and
      paravalvular leakage. Further technological improvements are, therefore, required
      before the indications for TAVI can be extended to young and low-risk patients
      with aortic stenosis. Many new-generation TAVI devices are currently in the early
      stages of clinical evaluation. Modifications in the new devices include the
      ability to reposition the valve before final deployment, features to reduce
      paravalvular leakage, and the introduction of low-profile delivery systems. The
      aim of this Review is to provide an overview of the new-generation transcatheter
      valvular technologies, including initial clinical reports. 

PMID- 24445488
TI  - Emerging advances in nanomedicine with engineered gold nanostructures.
AB  - Gold nanostructures possess unique characteristics that enable their use as
      contrast agents, as therapeutic entities, and as scaffolds to adhere functional
      molecules, therapeutic cargo, and targeting ligands. Due to their ease of
      synthesis, straightforward surface functionalization, and non-toxicity, gold
      nanostructures have emerged as powerful nanoagents for cancer detection and
      treatment. This comprehensive review summarizes the progress made in nanomedicine
      with gold nanostructures (1) as probes for various bioimaging techniques
      including dark-field, one-photon and two-photon fluorescence, photothermal
      optical coherence tomography, photoacoustic tomography, positron emission
      tomography, and surface-enhanced Raman scattering based imaging, (2) as
      therapeutic components for photothermal therapy, gene and drug delivery, and
      radiofrequency ablation, and (3) as a theranostic platform to simultaneously
      achieve both cancer detection and treatment. Distinct from other published
      reviews, this article also discusses the recent advances of gold nanostructures
      as contrast agents and therapeutic actuators for inflammatory diseases including
      atherosclerotic plaque and arthritis. For each of the topics discussed above, the
      fundamental principles and progress made in the past five years are discussed.
      The review concludes with a detailed future outlook discussing the challenges in
      using gold nanostructures, cellular trafficking, and translational considerations
      that are imperative for rapid clinical viability of plasmonic nanostructures, as
      well as the significance of emerging technologies such as Fano resonant gold
      nanostructures in nanomedicine. 

PMID- 24445489
TI  - Relapsing-remitting tumefactive demyelination.

PMID- 24445487
TI  - Potential drug targets for calcific aortic valve disease.
AB  - Calcific aortic valve disease (CAVD) is a major contributor to cardiovascular
      morbidity and mortality and, given its association with age, the prevalence of
      CAVD is expected to continue to rise as global life expectancy increases. No drug
      strategies currently exist to prevent or treat CAVD. Given that valve replacement
      is the only available clinical option, patients often cope with a deteriorating
      quality of life until diminished valve function demands intervention. The
      recognition that CAVD results from active cellular mechanisms suggests that the
      underlying pathways might be targeted to treat the condition. However, no such
      therapeutic strategy has been successfully developed to date. One hope was that
      drugs already used to treat vascular complications might also improve CAVD
      outcomes, but the mechanisms of CAVD progression and the desired therapeutic
      outcomes are often different from those of vascular diseases. Therefore, we
      discuss the benchmarks that must be met by a CAVD treatment approach, and
      highlight advances in the understanding of CAVD mechanisms to identify potential
      novel therapeutic targets. 

PMID- 24445490
TI  - Responsive materials: a novel design for enhanced machine-augmented composites.
AB  - The concept of novel responsive materials with a displacement conversion
      capability was further developed through the design of new machine-augmented
      composites (MACs). Embedded converter machines and MACs with improved geometry
      were designed and fabricated by multi-material 3D printing. This technique proved
      to be very effective in fabricating these novel composites with tuneable elastic
      moduli of the matrix and the embedded machines and excellent bonding between
      them. Substantial improvement in the displacement conversion efficiency of the
      new MACs over the existing ones was demonstrated. Also, the new design trebled
      the energy absorption of the MACs. Applications in energy absorbers as well as
      mechanical sensors and actuators are thus envisaged. A further type of MACs with
      conversion ability, viz. conversion of compressive displacements to torsional
      ones, was also proposed. 

PMID- 24445491
TI  - Indole-3-acetic acid in plant-microbe interactions.
AB  - Indole-3-acetic acid (IAA) is an important phytohormone with the capacity to
      control plant development in both beneficial and deleterious ways. The ability to
      synthesize IAA is an attribute that many bacteria including both plant growth
      promoters and phytopathogens possess. There are three main pathways through which
      IAA is synthesized; the indole-3-pyruvic acid, indole-3-acetamide and indole-3
      acetonitrile pathways. This chapter reviews the factors that effect the
      production of this phytohormone, the role of IAA in bacterial physiology and in
      plant-microbe interactions including phytostimulation and phytopathogenesis. 

PMID- 24445495
TI  - What makes zeolitic imidazolate frameworks hydrophobic or hydrophilic? The impact
      of geometry and functionalization on water adsorption.
AB  - We demonstrate, by means of Grand Canonical Monte Carlo simulation on different
      members of the ZIF family, how topology, geometry, and linker functionalization
      drastically affect the water adsorption properties of these materials, tweaking
      the ZIF materials from hydrophobic to hydrophilic. We show that adequate
      functionalization of the linkers allows one to tune the host-guest interactions,
      even featuring dual amphiphilic materials whose pore space features both
      hydrophobic and hydrophilic regions. Starting from an initially hydrophobic
      material (ZIF-8), various degrees of hydrophilicity could be obtained, with a
      gradual evolution from a type V adsorption isotherm in the liquid phase to a type
      I isotherm in the gas phase. This behavior is similar to what was described
      earlier in families of hydrophobic all-silica zeolites, with hydrophilic
      "defects" of various strength, such as silanol nests or the presence of extra
      framework cations. 

PMID- 24445496
TI  - Timing of determining axillary lymph node status when neoadjuvant chemotherapy is
      used.
AB  - Neoadjuvant chemotherapy is the standard of care for patients with locally
      advanced breast cancer and is a reasonable alternative to adjuvant chemotherapy
      for those with large operable disease. Potential clinical advantages of
      neoadjuvant chemotherapy include the conversion of some patients requiring
      mastectomy to candidates for breast-conserving surgery, the potential for
      downstaging axillary nodes and thus reducing the extent of axillary surgery, and
      the ability to correlate clinical and pathologic response to neoadjuvant
      chemotherapy with improved long-term outcomes. An important and controversial
      locoregional therapy issue in patients who are candidates for neoadjuvant
      chemotherapy relates to the timing of sentinel lymph node biopsy - i.e., either
      before or after neoadjuvant chemotherapy. This review will focus on the
      performance characteristics of sentinel lymph node biopsy before vs. after
      neoadjuvant chemotherapy and on the pros and cons of each approach. 

PMID- 24445497
TI  - Endoglin for targeted cancer treatment.
AB  - Endoglin is a homodimeric cell membrane glycoprotein receptor for transforming
      growth factor beta and bone morphogenetic proteins. Endoglin is essential for
      angiogenesis, being densely expressed on proliferating endothelial cells and
      upregulated during hypoxia. Its expression is implicated in development of
      resistance to vascular endothelial growth factor (VEGF) inhibition. TRC105 is an
      antibody that binds endoglin and prevents endothelial cell activation. Targeting
      endoglin and the VEGF pathway concurrently improves treatment in vitro and
      appears to reverse resistance to bevacizumab in some refractory cancer patients.
      Randomized trials are under way to assess the clinical benefit of adding TRC105
      therapy to bevacizumab therapy. Further trials are under way to assess the
      activity of TRC105 with small-molecule inhibitors of the VEGF pathway in renal
      cell carcinoma, hepatocellular carcinoma, and soft tissue sarcoma. Stratification
      of soft tissue sarcomas based on endoglin expression levels is proposed to
      identify patients most likely to benefit from TRC105 treatment. The development
      of a TRC105 antibody-drug conjugate is also described.

PMID- 24445498
TI  - Resectable, borderline resectable, and locally advanced pancreatic cancer: what
      does it matter?
AB  - Pancreatic adenocarcinoma represents a significant cause of morbidity and
      mortality in the modern era. Despite advances in the management of unresectable
      and advanced disease, the only potential avenue for cure at this time is
      resection. As our radiographic and surgical techniques have improved, we are
      better able to select patients who are the best candidates for a margin-negative
      resection, with or without the use of preoperative therapy. There is an emerging
      consensus on the definition of borderline resectable pancreatic cancer, but much
      work still needs to be done given the heterogeneous patient population,
      intervention, and outcome metrics used in previous retrospective and prospective
      studies. When designing future prospective trials of novel preoperative
      approaches, standardization of the stage of disease for the study population is
      essential to allow for accurate interpretation of study results. Ultimately, to
      make significant progress in localized pancreatic cancer, we urgently need
      effective novel therapeutic agents used in an optimal sequence with surgery. 

PMID- 24445499
TI  - Etirinotecan pegol: development of a novel conjugated topoisomerase I inhibitor.
AB  - Irinotecan is a very active chemotherapeutic agent used for the treatment of
      several malignancies, including colorectal cancer, gastroesophageal tumors, lung
      cancer, breast cancer, ovarian cancer, and primary brain tumors. Irinotecan
      exerts its antineoplastic effects through its active metabolite 7-ethyl-10
      hydroxycamptothecin. This metabolite is also responsible for the classic side
      effects associated with irinotecan that include diarrhea and neutropenia. A
      pegylated form of this agent, etirinotecan pegol, is undergoing clinical
      development with the main goal of increasing its therapeutic efficacy and its
      safety. This agent decreases the maximal exposure to 7-ethyl-10
      hydroxycamptothecin while providing continuous exposure to the treated tumor. The
      half-life of etirinotecan pegol is 50 days and it has been studied in different
      schedules: weekly, every other week, and once every 3 weeks. The maximum
      tolerated dose of etirinotecan pegol was found to be 145 mg/m(2). There have
      already been two phase II clinical trials published showing the efficacy of this
      novel agent in the treatment of metastatic ovarian and breast cancer. The side
      effect profile was acceptable for most patients, with a number of patients
      experiencing diarrhea and even neutropenia.

PMID- 24445500
TI  - Aflibercept--a decoy VEGF receptor.
AB  - Aflibercept (known as ziv-aflibercept in the USA and sold under the trade name
      Zaltrap(r)) is a human recombinant fusion protein with antiangiogenic effects
      that functions as a decoy receptor to bind vascular endothelial growth factors A
      and B and placental growth factor. Its unique mechanism of action with respect to
      other agents targeting angiogenesis led investigators to speculate that it may be
      more ubiquitously efficacious in tumors highly dependent on pathologic
      angiogenesis for their growth. Despite encouraging preclinical studies in various
      tumor types, aflibercept has not been proven efficacious in most later-phase
      clinical studies. In fact, its only currently held US Food and Drug
      Administration indication is in metastatic colorectal cancer in combination with
      5-fluorouracil, leucovorin, and irinotecan for those patients previously treated
      with an oxaliplatin-containing chemotherapy regimen. Given aflibercept's toxicity
      profile and cost, further investigation is needed to better understand its
      mechanism of action and to discover predictive biomarkers for optimization of its
      appropriate use in treatment of cancer patients.

PMID- 24445502
TI  - Naptumomab estafenatox: targeted immunotherapy with a novel immunotoxin.
AB  - Improvement of cancer therapy by introducing new concepts is still urgent even
      though there have been major advancements lately. Immunotherapy is well on the
      way to becoming an established tool in the cancer treatment armory. It seems that
      a combination of (1) activation of immune effector cells and selective targeting
      of them to tumors and (2) the inhibition of immune suppression often induced by
      the tumor itself are necessary to achieve the therapeutic goal. The immunotoxin
      naptumomab estafenatox was developed in an effort to activate and target the
      patient's own T cells to their tumor, by fusing a superantigen (SAg) variant that
      activates T lymphocytes to the Fab moiety of a tumor-reactive monoclonal
      antibody. Naptumomab estafenatox targets the 5T4 tumor antigen, a 72-kDa
      oncofetal trophoblast protein expressed on many carcinomas, including renal cell
      carcinoma. The therapeutic effect is associated with activation of SAg-binding T
      cells. The SAg-binding T lymphocytes expand, differentiate to effector cells, and
      infiltrate the tumor. The therapeutic efficacy is most likely related to the dual
      mechanism of tumor cell killing: (1) direct lysis by cytotoxic T lymphocytes of
      tumor cells expressing the antigen recognized by the antibody moiety of the
      fusion protein and (2) secretion of cytokines eliminating antigen-negative tumor
      cell variants. Naptumomab estafenatox has been clinically tested in a range of
      solid tumors with focus on renal cell carcinoma. This review looks at the
      clinical experience with the new immunotoxin and its potential.

PMID- 24445501
TI  - Endoscopic resection of sinonasal cancers.
AB  - Sinonasal malignancies, a rare group of tumors, are characterized by histological
      heterogeneity and poor survival. As improvements in image-guidance and endoscopic
      technologies became incorporated into head and neck oncologic and neurosurgical
      practice, the application of these technologies and techniques to the surgical
      management of sinonasal malignancy began. Over the past decade, there has been
      increasing evidence regarding the safety and oncological effectiveness of these
      techniques. Several institutions have reported their experience with endoscopic
      surgery and have shown reduced morbidity, better quality of life, and survival
      outcomes equivalent to those of open surgery in carefully selected patients.
      Endoscopic cranial base surgery is a rapidly evolving field. We review the
      literature on oncological outcomes, safety, quality of life, and recent
      technological advances. 

PMID- 24445503
TI  - Direct measurement of a 27-dimensional orbital-angular-momentum state vector.
AB  - The measurement of a quantum state poses a unique challenge for experimentalists.
      Recently, the technique of 'direct measurement' was proposed for characterizing a
      quantum state in situ through sequential weak and strong measurements. While this
      method has been used for measuring polarization states, its real potential lies
      in the measurement of states with a large dimensionality. Here we show the
      practical direct measurement of a high-dimensional state vector in the discrete
      basis of orbital angular momentum. Through weak measurements of orbital angular
      momentum and strong measurements of angular position, we measure the complex
      probability amplitudes of a pure state with a dimensionality, d=27. Further, we
      use our method to directly observe the relationship between rotations of a state
      vector and the relative phase between its orbital-angular-momentum components.
      Our technique has important applications in high-dimensional classical and
      quantum information systems and can be extended to characterize other types of
      large quantum states. 

PMID- 24445504
TI  - Vitamin B(12) status in children with cystic fibrosis and pancreatic
      insufficiency.
AB  - OBJECTIVES: Unexpectedly high serum B12 concentrations were noted in most study
      subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI)
      participating in a nutrition intervention at the baseline evaluation. The
      objectives of this study were to determine dietary, supplement-based, and enzyme
      based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status
      in children with CF and PI. STUDY DESIGN: Serum B12 status was assessed in
      subjects (5-18 years) and categorized as elevated (serum B12 above reference
      range for age and sex [Hi-B12]) or within reference range (serum B12 within
      reference range for age and sex) for age and sex. Serum homocysteine, plasma B6,
      red blood cell folate, height, weight, and body mass index z scores, pulmonary
      function, energy, and dietary and supplement-based vitamin intake were assessed.
      RESULTS: A total of 106 subjects, mean age 10.4 +/- 3.0 years, participated in
      the study. Median serum B12 was 1083 pg/mL, with 56% in the Hi-B12 group. Dietary
      and supplement-based B12 intakes were both high representing 376% and 667%
      recommended dietary allowance (RDA), respectively. The Hi-B12 group had
      significantly greater supplement-based B12 intake than the serum B12 within
      reference range for age and sex group (1000% vs 583% RDA, P < 0.001). Multiple
      logistic regression analysis showed that high supplement-based B12 intake and age
      >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume
      at 1 second (FEV1) decreased the risk (pseudo-R = 0.18, P < 0.001). CONCLUSIONS:
      Serum B12 was elevated in the majority of children with CF and PI. Supplement
      based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum
      B12 status. The health consequences of lifelong high supplement-based B12 intake
      and high serum B12 are unknown and require further study, as does the inversed
      correlation between serum B12 and forced expiratory volume at 1 second.

PMID- 24445505
TI  - Infantile intussusception.

PMID- 24445506
TI  - Origin of nanohole formation by etching based on droplet epitaxy.
AB  - Creating and manipulating materials at the nanoscale with controllable size,
      shape and nucleation site is an important task to meet the urgent demands for
      quantum structures with designed properties. In the last ten years, droplet
      epitaxy has been emerging as a versatile fabrication method for various complex
      nanostructures, such as quantum dots, quantum rings, double-rings, and so on.
      However, there is a lack of understanding of the deep nanohole formation based on
      droplet epitaxy at a high substrate temperature. Here we fabricate self-organized
      GaAs nanoholes by Ga droplet etching at high temperature based on droplet
      epitaxy, and they present good optoelectronic properties and have promising
      applications in fabrication of nanodevices due to their unique topology. A
      theoretical model is correspondingly proposed to explain the basic mechanism and
      simulate the time evolution of the nanohole structures. Our analysis shows that
      the morphology of the nanohole nanostructures can be well controlled through
      regulating experimental conditions. 

PMID- 24445507
TI  - Surgical considerations in locally advanced breast cancer patients receiving
      neoadjuvant chemotherapy.
AB  - PURPOSE OF REVIEW: The definition of locally advanced breast cancer (LABC)
      includes patients with large tumors, extensive regional lymph node involvement,
      or direct involvement of the skin or underlying chest wall. Neoadjuvant
      chemotherapy followed by surgery has become the standard of care and a valuable
      strategy in the multimodality management of LABC. Variations in practice exist
      and the purpose of this article is to explore the surgical considerations in the
      management of LABC. RECENT FINDINGS: There exist various diagnostic and treatment
      considerations in LABC patients that help guiding clinicians in the optimal
      management of LABC. The evolving concepts of breast conservation, immediate
      breast reconstruction and optimal management of the axilla are addressed.
      SUMMARY: LABC represents a heterogenous cohort of patients for whom a
      multidisciplinary care team is critical. A more detailed understanding of the
      surgical considerations will facilitate the optimal diagnostic evaluation and
      management of these patients.

PMID- 24445508
TI  - Paediatric oropharyngeal and cutaneous candidiasis with special reference to
      Candida dubliniensis.
AB  - Mucocutaneous and cutaneous candidiasis, though common in children, is often
      under-reported. The prevalence of Candida dubliniensis in causing these
      infections in this age group is also largely unknown. A prospective
      epidemiological cross-sectional study for candidiasis was performed in paediatric
      patients clinically suspected of candidiasis with oropharyngeal lesions (75
      patients), cutaneous lesions (18 patients) and lesions at both sites (2
      patients). Candida species were identified by conventional tests. For C.
      dubliniensis, chlamydospore production, growth on tobacco agar and growth at 45 
      degrees C were performed. Nine isolates were confirmed at a reference centre. The
      rates of candidiasis were 77.3 % (58 out of 75 patients clinically suspected of
      candidiasis) and 83.3 % (15/18) in oropharyngeal and cutaneous lesions
      respectively, and 1 of the 2 children with lesions at both sites was diagnosed as
      having chronic mucocutaneous candidiasis due to C. dubliniensis. The commonest
      species isolated was Candida albicans, in 41 (70.7 %) patients with oropharyngeal
      candidiasis and 11 (73.3 %) with cutaneous lesions; C. dubliniensis was isolated
      from 11 and 3 children respectively. In the paediatric population, C. albicans
      predominates in mucocutaneous and cutaneous candidiasis, with C. dubliniensis
      also contributing substantially.

PMID- 24445509
TI  - Characterization and antigenicity of recombinant Campylobacter jejuni flagellar
      capping protein FliD.
AB  - Campylobacter jejuni, a flagellated, spiral-rod, Gram-negative bacterium, is the
      leading pathogen of human acute bacterial gastroenteritis worldwide, and chickens
      are regarded as a major reservoir of this micro-organism. Bacterial flagella,
      composed of more than 35 proteins, play important roles in colonization and
      adhesion to the mucosal surface of chicken caeca. In this study, the flagellar
      capping protein, FliD, encoded by the fliD gene, from the Campylobacter jenuni D1
      39 isolate was expressed and characterized, and its antigenicity determined. The
      fliD gene comprised 1929 nt, potentially encoding a 642 aa peptide with a
      calculated molecular mass of 69.6 kDa. This gene was PCR amplified and
      overexpressed in Escherichia coli. The recombinant FliD protein was purified by
      cobalt-chelating affinity chromatography and confirmed by nucleotide sequencing
      of the expression plasmid, SDS-PAGE analysis, His tag detection and matrix
      assisted laser desorption/ionization time of flight mass spectrometry. The
      immunoblot data showed that the purified recombinant FliD protein reacted
      strongly to sera from broiler chickens older than 4 weeks, indicating that anti
      FliD antibody may be prevalent in the poultry population. These results provide a
      rationale for further evaluation of the FliD protein as a vaccine candidate for
      broiler chickens to improve food safety for poultry.

PMID- 24445510
TI  - Predictive value of direct nitrate reductase assay and its clinical performance
      in the detection of multi- and extensively drug-resistant tuberculosis.
AB  - Conventional culture and drug susceptibility testing (DST) methods for
      Mycobacterium tuberculosis are laborious and time consuming. For this reason
      alternative rapid culture and DST techniques are urgently needed to shorten the
      time for drug-resistance detection. A total of 222 smear-positive sputum samples
      were evaluated by the direct nitrate reductase assay (D-NRA) on Lowenstein-Jensen
      medium, for the rapid and simultaneous detection of resistance to isoniazid,
      rifampicin, kanamycin and ofloxacin. p-Nitrobenzoic acid was also included for
      identification of the M. tuberculosis complex. Results were compared with the
      BACTEC MGIT 960 as gold standard. The general performance of the D-NRA was very
      good, reaching a global value of 97 %. D-NRA had a turn-around time of 16.9 days
      to obtain results while that of the indirect MGIT 960 system was 29 days. D-NRA
      is a low-cost technology, easy to set up in clinical laboratories and suitable to
      be used for DST of M. tuberculosis in all smear-positive samples.

PMID- 24445511
TI  - Chlamydia psittaci exposure in pet birds.
AB  - Chlamydia psittaci is a zoonotic pathogen with a wide range of avian hosts and
      may be transmitted to humans and cause severe disease. To assess the risk of
      psittacosis posed by pet birds, the seroprevalence of Chlamydia psittaci
      antibodies in 360 Eurasian siskins (Carduelis spinus), 289 oriental skylarks
      (Alauda arvensis) and 36 black-tailed grosbeaks (Coccothraustes migratorius) in
      Gansu province, north-western China was detected by an indirect haemagglutination
      assay. Twenty-seven out of 289 (9.34 %) Alauda arvensis, 45 out of 360 (12.50 %)
      Carduelis spinus and 2 out of 36 (5.56 %) Coccothraustes migratorius were
      positive for Chlamydia psittaci infection at a cut-off dilution of 1 : 16. The
      prevalence of Chlamydia psittaci was higher in Carduelis spinus (12.5 %) than in
      Alauda arvensis (9.34 %) and Coccothraustes migratorius (5.56 %); however, the
      differences were not statistically significant (P>0.05). Statistical analysis
      indicated that Chlamydia psittaci seroprevalence in adult pet birds (12.4 %,
      67/540) was significantly higher than that in juvenile pet birds (4.83 %, 7/145)
      (P<0.01). There was no statistical difference in Chlamydia psittaci
      seroprevalence between male (12.4 %) and female (8.27 %) birds. To our knowledge,
      this is the first report indicating the seroprevalence of Chlamydia psittaci
      exposure in pet birds in China. Our results indicate that close contact with pet
      birds poses the risk of zoonotic transmission of Chlamydia psittaci.

PMID- 24445512
TI  - Comparative proteomic analysis of Clostridium difficile isolates of varying
      virulence.
AB  - The soluble proteome of three Clostridium difficile strains of varying pathogenic
      potential, designated B-1, Tra 5/5 and 027 SM, were compared using differential
      in-gel electrophoresis in which the proteins of each strain were labelled with
      CyDyes. This enabled visual inspection of the 2D profiles of strains and
      identification of differentially expressed proteins using image analysis
      software. Unlabelled protein reference maps of the predominant proteins were then
      generated for each strain using 2D gel electrophoresis followed by protein
      sequencing of each spot using a Reflectron matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. Increased
      coverage of the proteome was achieved using 1D gel electrophoresis in a bottom-up
      approach using LC-MS/MS of 1 cm gel slices. A total of 888 different proteins
      were detected by comparative analysis of isolates grown in parallel for 64 h on
      blood agar plates. Of these, only 38 % were shared between all isolates. One
      hundred and ten proteins were identified as showing >=2-fold difference in
      expression between strains. Differential expression was shown in a number of
      potential virulence and colonization factors. Toxin B was detected in the more
      virulent strains B-1 and 027 SM, but not in the lower virulent strain Tra 5/5,
      despite all strains possessing an intact pathogenicity locus. The S-layer protein
      (Cwp2) was identified in strains 027 SM and Tra 5/5 but not strain B-1, and
      differences in the post-translational modification of SlpA were noted for strain
      B-1. The variant S-layer profile of strain B-1 was confirmed by genomic
      comparison, which showed a 58 kb insertion in the S-layer operon of strain B-1.
      Differential post-translation modification events were also noted in flagellar
      proteins, thought to be due to differential glycosylation. This study highlights
      genomic and proteomic variation of different Clostridium difficile strains and
      suggests a number of factors may play a role in mediating the varying virulence
      of these different strains.

PMID- 24445513
TI  - Comparison of relapse and treatment failure rates among patients with
      neuromyelitis optica: multicenter study of treatment efficacy.
AB  - IMPORTANCE: Neuromyelitis optica (NMO) is an inflammatory disease of the optic
      nerves and spinal cord that leads to blindness and paralysis. Effective
      immunosuppression is the standard of care for relapse prevention. OBJECTIVE: To
      compare the relapse and treatment failure rates among patients receiving the 3
      most common forms of immunosuppression for NMO: azathioprine, mycophenolate
      mofetil, and rituximab. DESIGN, SETTING, AND PARTICIPANTS: We performed a
      retrospective, multicenter analysis of relapses in 90 patients with NMO and NMO
      spectrum disorder treated with azathioprine, mycophenolate, and/or rituximab at
      the Mayo Clinic and the Johns Hopkins Hospital during the past 10 years. MAIN
      OUTCOME AND MEASURE: Annualized relapse rates. RESULTS: Rituximab reduced the
      relapse rate up to 88.2%, with 2 in 3 patients achieving complete remission.
      Mycophenolate reduced the relapse rate by up to 87.4%, with a 36% failure rate.
      Azathioprine reduced the relapse rate by 72.1% but had a 53% failure rate despite
      concurrent use of prednisone. CONCLUSIONS AND RELEVANCE: Initial treatment with
      rituximab, mycophenolate, and, to a lesser degree, azathioprine significantly
      reduces relapse rates in NMO and NMO spectrum disorder patients. Patients for
      whom initial treatment fails often achieve remission when treatment is switched
      from one to another of these drugs.

PMID- 24445514
TI  - Rapid learning for precision oncology.
AB  - The emerging paradigm of Precision Oncology 3.0 uses panomics and sophisticated
      methods of statistical reverse engineering to hypothesize the putative networks
      that drive a given patient's tumour, and to attack these drivers with
      combinations of targeted therapies. Here, we review a paradigm termed Rapid
      Learning Precision Oncology wherein every treatment event is considered as a
      probe that simultaneously treats the patient and provides an opportunity to
      validate and refine the models on which the treatment decisions are based.
      Implementation of Rapid Learning Precision Oncology requires overcoming a host of
      challenges that include developing analytical tools, capturing the information
      from each patient encounter and rapidly extrapolating it to other patients,
      coordinating many patient encounters to efficiently search for effective
      treatments, and overcoming economic, social and structural impediments, such as
      obtaining access to, and reimbursement for, investigational drugs. 

PMID- 24445515
TI  - Skin cancer: Setting the stage for cutaneous SCC.

PMID- 24445516
TI  - Mitigating the toxic effects of anticancer immunotherapy.
AB  - Advances in our understanding of the regulatory mechanisms of the immune system
      have led to the development of novel approaches for cancer therapy, including
      inhibition of immune checkpoints with anti-CTLA-4 and anti-PD-1 antibodies. An
      increasing number of immunomodulatory treatments are under investigation, and are
      beginning to show promise in clinical trials. As more-effective therapies become
      available based on modulation of the immune system in order to trigger or enhance
      antitumour immune responses, clinicians will need to become familiar with
      recognizing and controlling the adverse effects arising from immune therapy. This
      Review describes the toxicity profiles for various anticancer therapies based on
      the use of agents that block immune checkpoints, immunostimulatory agents, and
      adoptive T-cell therapy (that is, infusion of modified autologous T cells). The
      management of patients receiving these treatments presents unique challenges for
      clinicians. Nevertheless, many of the adverse effects associated with these
      treatments are reversible and can be managed with supportive care either with or
      without cessation of therapy. This final point is extremely important given the
      continued development of new cancer immunotherapies, and the importance of safe
      and effective use of existing effective FDA-approved agents. 

PMID- 24445518
TI  - Cervical cancer in 2013: Screening comes of age and treatment progress continues.

PMID- 24445519
TI  - Lung cancer in 2013: Refining standard practice and admitting uncertainty.

PMID- 24445520
TI  - Colorectal cancer in 2013: Towards improved drugs, combinations and patient
      selection.

PMID- 24445517
TI  - Molecular analysis of circulating tumour cells-biology and biomarkers.
AB  - Growing evidence for intratumour heterogeneity informs us that single-site
      biopsies fall short of revealing the complete genomic landscape of a tumour. With
      an expanding repertoire of targeted agents entering the clinic, screening tumours
      for genomic aberrations is increasingly important, as is interrogating the
      tumours for resistance mechanisms upon disease progression. Multiple biopsies
      separated spatially and temporally are impractical, uncomfortable for the patient
      and not without risk. Here, we describe how circulating tumour cells (CTCs),
      captured from a minimally invasive blood test-and readily amenable to serial
      sampling-have the potential to inform intratumour heterogeneity and tumour
      evolution, although it remains to be determined how useful this will be in the
      clinic. Technologies for detecting and isolating CTCs include the validated
      CellSearch((r)) system, but other technologies are gaining prominence. We also
      discuss how recent CTC discoveries map to mechanisms of haematological spread,
      previously described in preclinical models, including evidence for epithelial
      mesenchymal transition, collective cell migration and cells with tumour
      initiating capacity within the circulation. Advances in single-cell molecular
      analysis are enhancing our ability to explore mechanisms of metastasis, and the
      combination of CTC and cell-free DNA assays are anticipated to provide invaluable
      blood-borne biomarkers for real-time patient monitoring and treatment
      stratification. 

PMID- 24445521
TI  - Haematological malignancies: Double act in follicular lymphoma.

PMID- 24445522
TI  - Polypharmacy and excessive polypharmacy in octogenarians and older acutely
      hospitalized patients.
AB  - AIM: The aim of this study was to assess the occurrence of polypharmacy and
      excessive polypharmacy in very old hospitalized patients based on their
      comorbidities. METHODS: The documentation of patients aged 80 years or older
      admitted to our department in the year 2010 was analyzed. Based on the Charlson
      index of comorbidity, a multiple logistic regression model with stepwise backward
      elimination was performed. Patients were stratified by gender and four age
      groups, and factors of a change in the number of medications during the hospital
      stay were assessed. RESULTS: Chronic pulmonary disease [odds ratio (OR): 2.40],
      diabetes mellitus with (OR: 4.65) or without (OR: 1.65) microvascular
      complications, congestive heart failure (OR: 2.37), connective tissue disease
      (OR: 3.02), and peripheral vascular disease (OR: 2.30) were statistically
      significantly associated with polypharmacy, while some of these diseases were
      also associated with excessive polypharmacy. The number of medications showed a
      gradual decrease with age, which was concordant with a decrease in total Charlson
      index score. "Admission for myocardial infarction" was associated with an
      increase in pharmaceuticals during hospital stay, whereas a known diagnosis of
      dementia or metastatic malignant disease was protective against a further
      increase in medications. CONCLUSIONS: Several medical conditions seem to
      predispose to polypharmacy in very old patients. To attain old age seems to be
      associated with few comorbidities, which reduces the need for a high number of
      pharmaceuticals. Physicians should pay attention to the identified predictors in
      very old patients, as polypharmacy may lead to adverse events and unnecessary
      hospitalization.

PMID- 24445523
TI  - [Research of the month].

PMID- 24445526
TI  - Analysis of surface EMG baseline for detection of hidden muscle activity.
AB  - OBJECTIVE: This study explored the feasibility of detecting hidden muscle
      activity in surface electromyogram (EMG) baseline. APPROACH: Power spectral
      density (PSD) analysis and multi-scale entropy (MSE) analysis were used. Both
      analyses were applied to computer simulations of surface EMG baseline with the
      presence (representing activity data) or absence (representing reference data) of
      hidden muscle activity, as well as surface electrode array EMG baseline
      recordings of healthy control and amyotrophic lateral sclerosis (ALS) subjects.
      MAIN RESULTS: Although the simulated reference data and the activity data yielded
      no distinguishable difference in the time domain, they demonstrated a significant
      difference in the frequency and signal complexity domains with the PSD and MSE
      analyses. For a comparison using pooled data, such a difference was also observed
      when the PSD and MSE analyses were applied to surface electrode array EMG
      baseline recordings of healthy control and ALS subjects, which demonstrated no
      distinguishable difference in the time domain. Compared with the PSD analysis,
      the MSE analysis appeared to be more sensitive for detecting the difference in
      surface EMG baselines between the two groups. SIGNIFICANCE: The findings implied
      the presence of a hidden muscle activity in surface EMG baseline recordings from
      the ALS subjects. To promote the presented analysis as a useful diagnostic or
      investigatory tool, future studies are necessary to assess the pathophysiological
      nature or origins of the hidden muscle activity, as well as the baseline
      difference at the individual subject level.

PMID- 24445527
TI  - Matrix Gla protein (MGP) promoter polymorphic variants and its serum level in
      stenosis of coronary artery.
AB  - Although the role of matrix Gla protein (MGP) is not completely known but, its
      expression within subendothelial macrophages and vascular smooth muscle cells is
      suggested to be involved in vascular calcification. In this study, we
      investigated the associations between the serum MGP levels and the MGP promoter
      high minor allele frequency (MAF) variants with the development of stenosis in
      coronary arteries. Moreover, we evaluated the allele changes within predicted
      transcription factor elements with bioinformatics tools. 182 subjects were
      recruited from who underwent coronary angiography. The MGP promoter rs1800801,
      rs1800802 and rs1800799 genotypes and haplotypes were detected by ARMS-RFLP PCR
      techniques. The serum MGP concentration was measured using ELISA method. Jaspar
      profiles were used for scoring the polymorphic variations within the
      transcription factor elements. The genotype and two-allelic haplotype
      distributions were not significant between the patient and control groups (P >
      0.05). The serum MGP levels had not significant differences between the genotypes
      (P > 0.1) and haplotypes (P > 0.4). Based on the prediction studies, we did not
      observe significant differences between the polymorphic scores in the predicted
      elements (P > 0.05). We concluded that the genotype and haplotype distributions
      of the MGP promoter high-MAF polymorphisms, as confirmed in the prediction
      studies and the serum MGP level are not significantly associated with the
      coronary artery disease. Based on the study results, the MGP protein did not play
      an important role in the development of stenosis of coronary arteries. 

PMID- 24445528
TI  - Transcriptional activation of p21(WAF1/CIP1) is mediated by increased DNA binding
      activity and increased interaction between p53 and Sp1 via phosphorylation during
      replicative senescence of human embryonic fibroblasts.
AB  - Although p21(WAF1/CIP1) is known to be elevated during replicative senescence of
      human embryonic fibroblasts (HEFs), the mechanism for p21 up-regulation has not
      been elucidated clearly. In order to explore the mechanism, we analyzed
      expression of p21 mRNA and protein and luciferase activity of full-length p21
      promoter. The result demonstrated that p21 up-regulation was accomplished largely
      at transcription level. The promoter assay using serially-deleted p21 promoter
      constructs revealed that p53 binding site was the most important site and Sp1
      binding sites were necessary but not sufficient for transcriptional activation of
      p21. In addition, p53 protein was shown to interact with Sp1 protein. The
      interaction was increased in aged fibroblasts and was regulated by
      phosphorylation of p53 and Sp1. DNA binding activity of p53 was significantly
      elevated in aged fibroblasts but that of Sp1 was not. DNA binding activities of
      p53 and Sp1 were also regulated by phosphorylation. Phosphorylation of p53 at
      serine-15 and of Sp1 at serines appears to be involved. Taken together, the
      result demonstrated that p21 transcription during replicative senescence of HEFs
      is up-regulated by increase in DNA binding activity and interaction between p53
      and Sp1 via phosphorylation.

PMID- 24445529
TI  - Authentication of animal signatures in traditional Chinese medicine of Lingyang
      Qingfei Wan using routine molecular diagnostic assays.
AB  - Lingyang Qingfei Wan produced by Beijing TongRenTang is a long-standing and
      popular medicine in China and international pharmaceutical markets. Concerns
      continue to be raised about the legality of usage of saiga antelope, which was
      defined as endangered species by Convention on International Trade in Endangered
      Species of Wild Fauna and Flora legislation and internal legislation in China.
      Therefore, the alternative pill in which substitutes saiga antelope with goat in
      the formula of Lingyang Qingfei Wan was developed. In order to authenticate the
      origin of animal contents in Lingyang Qingfei Wan and its alternative pill,
      molecular diagnostic assay was utilized by mtDNA polymorphism analysis. Four
      universal primer pairs containing mtDNA 12SrRNA, 16SrRNA, cytochrome b gene and
      cytochrome oxidase I were employed to obtain species-specific sequences of saiga
      antelope and goat, and multiple species-specific primer pairs for saiga antelope
      and goat were used to identify the animal origin in patent pills according to
      nucleotide polymorphisms between the two species. In additions, alternative
      techniques were attempted surrounding dilemmas of low concentration of target
      DNAs and presence of PCR-inhibitory substances in organic ingredients within
      complex pill. Results revealed that all species-specific primers could be
      successfully used for authentication of animal origin within complex pill, and
      sample preprocessing was critical during experimental manipulation. Internal
      positive control was an efficient and cost-effective way to assist in monitoring
      the potential interference from inhibitory substances which existed in the highly
      processed pills.

PMID- 24445530
TI  - Evaluation of TRPM (transient receptor potential melastatin) genes expressions in
      myocardial ischemia and reperfusion.
AB  - In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5,
      TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after
      ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were
      equally divided into three groups as follows: Group 1: control group (n:10),
      Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR
      (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The
      expression levels of the TRPM genes were analyzed by semi-quantitative reverse
      transcriptase-PCR. When compared to the ischemia control, the expression levels
      of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased.
      However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue.
      Histopathological analysis of the myocardial tissues showed that the structures
      that were most damaged were those exposed to IR. The findings showed that there
      is a positive relationship between TRPM7 expression and myocardial IR injury. 

PMID- 24445531
TI  - Changing trends in newly licensed RNs.
AB  - OBJECTIVE: Recent changes in U.S. health care and economics may influence the
      demand for nurses and the work choices of newly licensed RNs (NLRNs). We sought
      to compare the work lives of two cohorts of NLRNs licensed six years apart.
      METHODS: Data were collected from two groups of NLRNs in 14 states via mailed
      surveys. The first group consisted of a subset of NLRNs surveyed for a larger
      study in 2004-05; the second group was surveyed by similar methods in 2010-11.
      Responses were weighted to adjust for differences in response rates according to
      geographic area. RESULTS: Response rates were 58% and 47%, respectively, for the
      2004-05 cohort (N = 774) and the 2010-11 cohort (N = 1,613). The NLRNs in the
      later cohort were less likely to work in hospitals, special-care units, and
      direct care and more likely to work as managers, be enrolled in formal education
      programs, and view their work environments positively, resulting in more
      commitment to the organization. Also, those in the later cohort reported fewer
      local job opportunities, and a greater number held a second job CONCLUSIONS: :
      These findings indicate a shift from the traditional work patterns of NLRNs, who
      often began their careers in hospitals. Employers' heightened awareness of such
      changing trends among NLRNs may help them in planning for RN recruitment and
      retention.

PMID- 24445532
TI  - Posttonsillectomy pain in children.
AB  - Tonsillectomy, used to treat a variety of pediatric disorders, including
      obstructive sleep apnea, peritonsillar cellulitis or abscesses, and very frequent
      throat infection, is known to produce nausea, vomiting, and prolonged, moderate
      to-severe pain. The authors review the causes of posttonsillectomy pain, current
      findings on the efficacy of various pharmacologic and nonpharmacologic
      interventions in pain management, recommendations for patient and family teaching
      regarding pain management, and best practices for improving medication adherence.

PMID- 24445533
TI  - To each according to its degree: the meritocracy and topocracy of embedded
      markets.
AB  - A system is said to be meritocratic if the compensation and power available to
      individuals is determined by their abilities and merits. A system is topocratic
      if the compensation and power available to an individual is determined primarily
      by her position in a network. Here we introduce a model that is perfectly
      meritocratic for fully connected networks but that becomes topocratic for sparse
      networks-like the ones in society. In the model, individuals produce and sell
      content, but also distribute the content produced by others when they belong to
      the shortest path connecting a buyer and a seller. The production and
      distribution of content defines two channels of compensation: a meritocratic
      channel, where individuals are compensated for the content they produce, and a
      topocratic channel, where individual compensation is based on the number of
      shortest paths that go through them in the network. We solve the model
      analytically and show that the distribution of payoffs is meritocratic only if
      the average degree of the nodes is larger than a root of the total number of
      nodes. We conclude that, in the light of this model, the sparsity and structure
      of networks represents a fundamental constraint to the meritocracy of societies. 

PMID- 24445535
TI  - The structure of hyperalkaline aqueous solutions containing high concentrations
      of gallium--a solution X-ray diffraction and computational study.
AB  - Highly concentrated alkaline NaOH-Ga(OH)3 solutions with 1.18 M <= [Ga(III)]T <=
      2.32 M and 2.4 M <= [NaOH]T <= 4.9 M (where the subscript T denotes total or
      analytical concentrations) have been prepared and investigated by solution X-ray
      diffraction and also by ab initio quantum chemical calculations. The data
      obtained are consistent with the presence of only one predominant Ga(III)-bearing
      species in these solutions, which is the tetrahedral hydroxo complex Ga(OH)4(-).
      This finding is in stark contrast to that found for Al(III)-containing solutions
      of similar concentrations, in which, besides the monomeric complex, an oxo
      bridged dimer was also found to form. From the solution X-ray diffraction
      measurements, the formation of the dimeric (OH)3Ga-O-Ga(OH)3(2-) could not
      unambiguously be shown, however, from the comparison of experimental IR, Raman
      and (71)Ga NMR spectra with calculated ones, its formation can be safely
      excluded. Moreover, higher mononuclear stepwise hydroxo complexes, like Ga(OH)6(3
      ), which have been claimed to exist by others in the literature, were not
      possible to experimentally detect in these solutions with any of the
      spectroscopic techniques used.

PMID- 24445536
TI  - Human movement analysis as a measure for fatigue: a hidden Markov-based approach.
AB  - Fatigue influences the way a training exercise is performed and alters the
      kinematics of the movement. Monitoring the increase of fatigue during
      rehabilitation and sport exercises is beneficial to avoid the risk of injuries.
      This study investigates the use of a parametric hidden Markov model (PHMM) to
      estimate fatigue from observing kinematic changes in the way the exercise is
      performed. The PHMM is compared to linear regression. A top-level hidden Markov
      model with variable state transitions incorporates knowledge about the progress
      of fatigue during the exercise and the initial condition of a subject. The
      approach is tested on a squat database recorded with optical motion capture. The
      estimates of fatigue for a single squat, a set of squats, and an entire exercise
      correlate highly with subjective ratings. 

PMID- 24445534
TI  - A randomised, controlled trial of self-monitoring of blood glucose in patients
      with type 2 diabetes receiving conventional insulin treatment.
AB  - AIMS/HYPOTHESIS: We evaluated whether self-monitoring of blood glucose (SMBG)
      leads to better glycaemic control (HbA(1c)) in patients with type 2 diabetes on
      conventional insulin regimens. METHODS: Patients with type 2 diabetes on a
      conventional insulin regimen (basal or premixed insulin with or without
      additional oral glucose-lowering agents) were recruited at study centres led by
      members of the German Diabetes Association. In a randomised, prospective, open 2
      * 2 factorial design, the once-weekly performance of four-point glucose profiles
      (SMBG +; n = 151 patients) was compared with no SMBG (SMBG -; n = 149), and the
      measuring and transmitting of HbA1c results to the study centres (HbA(1c) +; n =
      158, of these 82 SMBG - and 76 SMBG +) was compared with HbA1c measurement
      without disclosure of results (HbA(1c) -; n = 142, of these 67 SMBG - and 75 SMBG
      +). Randomised allocation was carried out by a central office, using sequentially
      numbered, sealed envelopes. The primary endpoint was the reduction of HbA(1c)
      compared with baseline after 12 months. Secondary analyses were of therapy
      intensification in response to higher blood or urinary glucose or HbA(1c).
      Participants and caregivers were not blinded as to the allocation of
      interventions, whereas the laboratory determining HbA(1c) remained blinded.
      RESULTS: Patient characteristics were balanced across groups. A total of 56
      patients dropped out. In completers, HbA(1c) was reduced in the SMBG + group from
      7.3% to 7.0%, i.e. by 0.3% (0.1%, 0.5%) vs SMBG - from 7.3% to 7.0% and 0.3%
      (0.2%, 0.5%), respectively, the difference being 0.0% (-0.2%, 0.2%) (p = 0.93).
      The disclosure of HbA(1c) results had no significant influence, with a difference
      of 0.1% (-0.1%, 0.4%) (p = 0.28). Values above are mean (95% CI). The ORs for
      therapy intensification significantly rose as the following increased:
      proportions of urine samples testing positive for glucose, HbA1c concentrations,
      and fasting or postprandial glucose concentrations. No important adverse events
      were associated with the interventions. CONCLUSIONS/INTERPRETATION: SMBG profiles
      once weekly or the disclosure of HbA(1c) results did not improve glycaemic
      control in patients with type 2 diabetes on conventional insulin treatment,
      although indicators of hyperglycaemia increased the likelihood of therapy
      intensification. Greater intensification may be necessary to impact on glycaemic
      control. TRIAL REGISTRATION: www.clinicaltrials.gov (registration code
      NCT00688363) FUNDING: Deutsche Diabetes-Gesellschaft, Deutsche Diabetes-Stiftung,
      Bayer Vital GmbH.

PMID- 24445537
TI  - Successful closed reduction after adductor tenotomy in a 14-year-old boy with
      chronic hip dislocation in Down syndrome.
AB  - Dislocation or subluxation of the hip is considered as the most common hip
      problem in patients with Down syndrome. Recommended treatment of chronic
      dislocation treatment is open reduction combined with femoral and/or pelvis
      osteotomies. We report a Down syndrome child with chronic hip dislocation who was
      successfully treated with adductor tenotomy and closed reduction, which has not
      been reported previously. 

PMID- 24445539
TI  - The effect of anxiety about falling on selected physiological parameters with
      different rope protocols in sport rock climbing.
AB  - BACKGROUND: The aim of this study was to examine the effect of anxiety about
      falling on selected physiological parameters on the lead (LC) and top-rope
      climbing (TRC) methods. For this purpose the physical differences between the two
      methods have been eliminated and the effect of only the anxiety about falling on
      the physiological parameters has been studied. METHODS: A total of 26
      intermediate level sport rock climbers, 22 male and 4 female with an average age
      of 27.73 +/- 6.67 yr have participated as volunteers in the study. The average
      height of the participants was 177 +/- 8.01 cm and body weight was 71.38 +/-
      13.19 kg. Their average climbing age was 6.61 +/- 4.84 and lead climbing age was
      5.71 +/- 4.35 yr. The participants have climbed the same route, one with LC and
      the other with the TRC method. 20 minutes before the climbing The Competitive
      State Anxiety Inventory - 2 (CSAI-2) was completed by each participant. The
      physiological parameters measured on both of the two climbing days were the HR,
      VE, VO2 mL.kg-1.min-1, RER and MET with a mobile gas analyzer. RESULTS: The
      difference between the results obtained in all the three subscales of the CSAI-2
      average comparisons was found to be statistically significant. The cognitive
      anxiety and somatic anxiety points were found to be high in LC and self
      confidence points to be low in LC. No statistically significant difference was
      found between the two climbing times. It suggests that the physical conditions
      could be equalized between the two methods. A statistically significant
      difference was found in the average comparisons of the VE, VO2 mL.kg-1.min-1, RER
      and MET values. Even though HR values are higher during lead climbing, HR
      difference between the two methods was not statistically significant. CONCLUSION:
      Energy and oxygen consumption and the level of anxiety are greater during LC as
      compared to TRC.

PMID- 24445540
TI  - Ground reaction force patterns represent the level of training.
AB  - BACKGROUND: Hopping dependent on speed causes different characteristics of ground
      reaction force pattern. Strongly set training-specific stimuli equally induce a
      corresponding characteristic of the force shape that is widely independent of
      hopping frequency. Thus it could be shown that 'jumpers' still generate a single
      modal force pattern with slow frequencies. Concerning other athletes, it only
      exists around the preferential frequency of motion. On this account we raised the
      question whether different types of sports are differentiated by the ground
      reaction force pattern and whether conclusions on the level of training could be
      made. METHODS: Twenty-one athletes took part in the study. They had to perform
      speed depending hopping series. Since only the shape of force course was of
      interest, a normalisation was conducted. Additionally, this force shape was
      compared with a so-called 'standard-course'. The degree of variance was formed by
      the sum of residuals. RESULTS: The ground reaction force differs from the
      standard course significantly with the reduction of the frequency of motion. The
      analysis of the test persons resulted in five different highly-significant
      clusters which are directly related to the contents of training (strength,
      endurance, etc.). With increasing performance level, the sum of residuals
      decreases most significantly. With the underlying method athletes from different
      types of sport can be classified. Furthermore, the item obtained by the analysis
      allows statements about the particular level of performance. CONCLUSION: On the
      basis of the presented results this procedure can be seen as a simple possibility
      for performance diagnostics.

PMID- 24445538
TI  - Kinase fusions are frequent in Spitz tumours and spitzoid melanomas.
AB  - Spitzoid neoplasms are a group of melanocytic tumours with distinctive
      histopathological features. They include benign tumours (Spitz naevi), malignant
      tumours (spitzoid melanomas) and tumours with borderline histopathological
      features and uncertain clinical outcome (atypical Spitz tumours). Their genetic
      underpinnings are poorly understood, and alterations in common melanoma
      associated oncogenes are typically absent. Here we show that spitzoid neoplasms
      harbour kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%) and RET
      (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively
      active, stimulate oncogenic signalling pathways, are tumourigenic and are found
      in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz
      naevi, 56% of atypical Spitz tumours and 39% of spitzoid melanomas. Kinase
      inhibitors suppress the oncogenic signalling of the fusion proteins in vitro. In
      summary, kinase fusions account for the majority of oncogenic aberrations in
      spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid
      melanomas. 

PMID- 24445541
TI  - Predictors of competitive achievement among pubescent synchronized swimmers: an
      analysis of the solo-figure competition.
AB  - AIM: This study examined the applicability of sport-specific fitness tests
      (SSTs), anthropometrics, and respiratory parameters in predicting competitive
      results among pubescent synchronized swimmers. METHODS: A total of 25
      synchronized swimmers (16-17 years; 166.2 +/- 5.4 cm; and 58.4 +/- 4.3 kg)
      volunteered for this study. The independent variables were body mass, body
      height, Body Mass Index (BMI), body fat percentage (BF%), lean body mass
      percentage, respiratory variables, and four SSTs (two specific power tests plus
      one aerobic- and one anaerobic-endurance test). The dependent variable was
      competitive achievement in the solo figure competition. The reliability analyses,
      Pearson's correlation coefficient and forward stepwise regression were
      calculated. RESULTS: The SSTs were reliable for testing fitness status among
      pubescent synchronized swimmers. The forward stepwise regression retained two
      SSTs, BF% and forced vital capacity (FVC, relative for age and stature) in a set
      of predictors of competitive achievement. Significant Beta coefficients are found
      for aerobic-endurance, SST and FVC. CONCLUSION: The sport-specific measure of
      aerobic endurance and FVC appropriately predicted competitive achievement with
      regard to the figures used in the competition when competitive results (the
      dependent variable) were obtained. Athletes and coaches should be aware of the
      probable negative influence of very low body fat levels on competitive
      achievement.

PMID- 24445542
TI  - Detraining in young soccer players.
AB  - BACKGROUND: Two types of detraining can be described: short-term detraining with
      a period of less than 4 weeks, and long-term detraining (period longer than 4
      weeks). The purpose of this study is to verify the presence and eventually the
      magnitude of physiological cardiorespiratory changes in young team sport players
      after a period of long-term detraining. METHODS: Fourteen young soccer players
      (15 +/- 1 year) were studied with two incremental tests at the end of the regular
      season and after a six-week total break period from training activities.
      Physiological variables were evaluated: heart rate (HR), oxygen uptake (VO2),
      volume of ventilation (VE), aerobic (VA) and anaerobic (Van) running speed at
      thresholds and maximum effort were recorded. RESULTS: This study shows the
      magnitude of the physiological changes in young players after a period of long
      term detraining. The results showed significant decreases at the end of the
      detraining period of VO2 at VA of 22.7% (44.54 +/- 4.56 vs. 34.41 +/- 4.57
      mL/kg/min, P<0.05), of 25.8% of VO2 at VAn (54.60 +/- 5.81 vs. 40.48 +/- 5.07
      mL/kg/min, P<0.05) and of 21.2% in VO2 max (62.83 +/- 5.77 vs. 49.46 +/- 6.51
      mL/kg/min, P<0.05). Speed at VA (11.5 +/- 0.96 vs. 10.7 +/- 0.97 km/h; P<0.05),
      speed at VAn (15.3 +/- 1.05 vs. 14.2 +/- 1.48 km/h; P<0.05), peak running speed
      (18.8 +/- 1.20 vs. 17.2 +/- 1.1 km/h; P<0.05). CONCLUSION: It is likely that
      alteration of metabolic parameters may significantly affect the range of physical
      condition and especially, aerobic-anaerobic resistance and maintenance training
      would be advisable in young athletes during the transition period. Given the
      relevance of worsening demonstrated by our data, coaches should avoid very long
      periods of complete rest (no more than 15 days) at the end of the season.

PMID- 24445543
TI  - Preparation for and physiological responses to competing in the Marathon des
      Sables: a case report.
AB  - A case study into the preparation and physiological responses of competing in the
      Marathon des Sables (MDS) was conducted by preparing a male competitor for, and
      monitoring him during, his first attempt at the race. The aims of this case
      report were to (a) prepare and monitor an ex-Olympic, male rower (S1) during the
      2010 race and; (b) compare his physiological responses and race performance to
      that of the current MDS record holder (S2). S1 (age 37 y; body mass 94.0 kg;
      height 1.92 m; VO(2peak) 66.0 ml.kg-1.min-1) and S2 (age 37 y; body mass 60.8 kg;
      height 1.68 m; VO(2peak) 65.9 ml.kg-1.min-1) completed a heat test and S1
      subsequently underwent 7 d of heat acclimation prior to the MDS. Gastro
      intestinal temperature (Tgi) and heart rate (HR) were measured for S1 during
      Stages 2, 4, and 5 of the MDS and pre- and post-stage body mass, and urine
      specific gravity were measured for all stages. Race time and average speeds were
      collected for S1 and S2. Total race times for S1 and S2 were 25:29:35 and
      19:45:08 h:min:s. S1's mean (+/- 1 SD) percentage HR range (%HRR=[HR
      HRmin]/[HRmax-HRmin]x100) was 66.1 +/- 13.4% and Tgi ranged between 36.63-39.65
      degrees C. The results provide a case report on the physiological responses of a
      highly aerobically-trained, but novice ultra-endurance runner competing in the
      MDS, and allow for a comparison with an elite performer.

PMID- 24445544
TI  - Self-paced cycling performance and recovery under a hot and highly humid
      environment after cooling.
AB  - AIM: This study investigated the effects of pre- and post-cooling on self-paced
      time-trial cycling performance and recovery of cyclists exercising under a hot
      and highly humid environment (29.92  degrees C-78.52% RH). METHODS: Ten male
      cyclists performed a self-paced 20-min time trial test (TT20) on a cyclo
      ergometer while being cooled by a cooling vest and a refrigerating headband
      during the warm-up and the recovery period. Heart rate, power output, perceived
      exertion, thermal comfort, skin and rectal temperatures were recorded. RESULTS:
      Compared to control condition (222.78 +/- 47 W), a significant increase (P<0.05)
      in the mean power output during the TT20 (239.07 +/- 45 W; +7.31%) was recorded
      with a significant (P<0.05) decrease in skin temperature without affecting
      perceived exertion, heart rate, or rectal temperature at the end of the TT20.
      However, pace changes occurred independently of skin or rectal temperatures
      variations but a significant difference (P<0.05) in the body's heat storage was
      observed between both conditions. This result suggests that a central programmer
      using body's heat storage as an input may influence self-paced time-trial
      performance. During the recovery period, post-cooling significantly decreased
      heart rate, skin and rectal temperatures, and improved significantly (P<0.05)
      thermal comfort. CONCLUSION: Therefore, in hot and humid environments, wearing a
      cooling vest and a refrigerating headband during warm-up improves self-paced
      performance, and appears to be an effective mean of reaching skin rest
      temperatures more rapidly during recovery.

PMID- 24445545
TI  - Effects of a 25-km trial on psychological, physiological and stroke
      characteristics of short- and mid-distance swimmers.
AB  - AIM: The aim of this paper was to evaluate the effects of a very long distance
      swimming task on psychological, biomechanical and physiological responses. Eight
      swimmers (age 21.0 +/- 1.2 years; stature 1.80 +/- 0.07 m; body mass 76.7 +/-
      11.0 kg; means +/- SD) participated in a 25-km trial in a swimming pool. METHODS:
      Before and immediately after the trial, swimmers underwent a 50-m sprint test,
      during which we assessed velocity, stroke rate (SR), stroke length (SL) and
      psychological condition (rate of perceived exertion [RPE] and profile of mood
      state [POMS] questionnaire). During the 25-km trial we determined also elbow
      angle, heart rate (HR) and lactate concentration ([La]). RESULTS: Velocity, SR
      and SL during the sprint test after the trial decreased compared to before from
      1.91 +/- 0.01 m.s-1, 0.94 +/- 0.01 cycles.s-1 and 1.99 +/- 0.02 m.cycle-1 to 1.45
      +/- 0.01 m.s-1, 0.78 +/- 0.01 cycles.s-1 and 1.84 +/- 0.03 m.cycle-1,
      respectively (P<0.05). During the 25-km trial, velocity and SL decreased
      significantly, while SR and elbow angle did not change. Velocity and SR during
      the sprint test after the trial were significantly higher than those during the
      trial. RPE and fatigue (POMS subscale) increased significantly, while the other
      negative POMS subscales and vigor decreased significantly. HR decreased
      significantly at 20 km, then increasing significantly at 25 km, while [La] did
      not change. CONCLUSION: These results suggest that, despite the occurrence of
      fatigue, as evidenced by the drop in velocity and changes in psychological
      profile, swimmers were able to complete the 25-km trial by adopting a
      conservative pacing, unveiling also a reserve in maximum performance.

PMID- 24445546
TI  - An antioxidant and multivitamin supplement reduced improvements in VO2max.
AB  - The aim of this study was to investigate the effect of an antioxidant supplement
      on training induced changes in VO2max in well-trained subjects. In a double
      blinded placebo controlled design, a total of 40 amateur soccer players and 14
      multi sports athletes were block-randomised into a placebo group or an
      antioxidant supplemented group (SUP). The SUP group consumed two commercially
      available antioxidant/vitamin supplements for 6 weeks according to manufacturer
      instructions (LifePak(r) Essentials Super A) and the placebo group took a similar
      amount of placebo tablets. Before and after the supplementation period, the
      athletes were tested for skin carotenoid score and VO2max. During the
      supplementation period all subjects continued their normal training in the
      preparation phase of the season. Six week supplementation with the antioxidant
      vitamin/mineral supplement increased skin carotenoid score by 27 +/- 6% while no
      change was observed in the placebo group. VO2max increased by 5.6 +/- 2.0% in the
      placebo group while no change was observed in the SUP group. The relative
      increase in VO2max was significantly higher in the placebo group than in the SUP
      group. In conclusion, the antioxidant vitamin/mineral supplement used in this
      study seemed to reduce training efficiency indicated by the lack of increase in
      VO2max in the SUP group.

PMID- 24445547
TI  - The King-Devick test as a concussion screening tool administered by sports
      parents.
AB  - BACKGROUND: Sports-related concussion has received increasing awareness due to
      short- and long-term neurologic sequelae seen among athletes. The King-Devick (K
      D) test captures impairment of eye movements and other correlates of suboptimal
      brain function. We investigated the K-D test as a screening for concussion when
      administered by layperson sports parents in a cohort of amateur boxers. METHODS:
      The K-D test was administered pre-fight and post-fight by laypersons masked to
      the head trauma status of each athlete. Matches were watched over by a ringside
      physician and boxing trainer. Athletes with suspected head trauma received
      testing with the Military Acute Concussion Evaluation (MACE) by the ringside
      physician to determine concussion status. Athletes sustaining concussion were
      compared to the athletes screened using the K-D test. RESULTS: Post-fight K-D
      scores were lower (better) than the best baseline score (41 vs. 39.3 s, P=0.34,
      Wilcoxon signed-rank test), in the absence of concussion. One boxer sustained a
      concussion as determined by the ringside physician. This boxer was accurately
      identified by the layperson K-D testers due to a worsening in K-D test compared
      to baseline (3.2 seconds) and an increased number of errors. High levels of test
      retest reliability were observed (intraclass correlation coefficient 0.90 [95% CI
      0.84-0.97]). Additionally, 6 boxers who participated in multiple bouts showed no
      worsening of their K-D times further supporting that scores are not affected by
      the fatigue associated with sparring. CONCLUSION: The K-D test is a rapid
      sideline screening tool for concussion that can be effectively administered by
      non-medically trained laypersons.

PMID- 24445548
TI  - Training-related risk factors in the etiology of overuse injuries in endurance
      sports.
AB  - AIM: The purpose of this study was to clarify training-related risk factors for
      overuse injuries. METHODS: This was twelve-month retrospective study which was
      done by self-reported postal questionnaire. The study group consisted of 446 men
      and women top-level Finnish athletes representing three different endurance
      sports (cross-country skiing, swimming, long-distance running) between the ages
      of 15-35. Self-reported anthropometric and training-related variables (such as
      starting age of training, years of active training, hours trained yearly,
      competition hours and weekly resting days) and occurrence of overuse injuries.
      RESULTS: Athletes with less than 2 rest days per week during the training season
      had 5.2-fold risk (95% confidence intervals [CI] 1.89-14.06, P=0.001) for an
      overuse injury, and athletes who trained more than 700 hours during a year had
      2.1-fold risk (95% CI 1.21-3.61, P=0.008) for an overuse injury compared to the
      others. Athletes who reported a tendon injury were on average two years older
      than athletes without such an injury (P<0.001). CONCLUSION: We found that low
      number of recovery days and a high amount of training are training-related risk
      factors for overuse injuries in top-level endurance athletes. The higher number
      of tendon overuse injuries in older than younger athletes may indicate that age
      related degeneration plays an important role in the etiology of tendon injuries.
      These findings should be taken into account when planning exercise programs for
      endurance athletes.

PMID- 24445549
TI  - Humeral fracture in arm wrestling: bone morphology as a permanent risk factor.
      Indications for safety measures in arm wrestling.
AB  - BACKGROUND: Arm wrestling has been recognized as a popular and potentially
      dangerous competition. Reports on injuries related to arm wrestling are
      increasing. The most important of these injuries are humeral shaft fractures. The
      generally accepted theory states that the shoulder joint is actively internally
      rotated against the opponent while the elbow is fixed in flexion resulting in
      enormous violent torque forces across the humeral shaft. METHODS: The reported
      fracture morphology seems similar so we theorized that the basis of this fracture
      type is the bone structure. There is no experimental model of the arm wrestling
      fracture other than a virtual one. We assess morphology of the humeral bone by
      means of the bone cutting procedures and to verify the theory that the structure
      of humeral bone is a basis of the arm-wrestling fracture by means of newly
      developed model on human bones. RESULTS: Results of the study suggest that the
      humeral shaft fracture morphology during arm wrestling is based on the spiral
      structure of the bone combined with the direction of the revolving, rotational
      force during the match. CONCLUSION: The safety rules of the arm-wrestling match
      based on results of our experimental study and the literature metaanalysis are
      also formulate.

PMID- 24445550
TI  - Impact of exercise intensity on cardiac function in adolescent runners.
AB  - BACKGROUND: Prolonged exercise may induce a transient reduction in the left
      ventricular (LV) function (exercise-induced cardiac fatigue) in adults. However,
      data related to the cardiovascular consequences of prolonged exercise in
      adolescents are extremely limited. This study examined the impact of exercise
      intensity adopted in routine long-distance run training on LV function in trained
      adolescent runners in a laboratory-based setting. METHODS: Twelve male adolescent
      runners (14.5 +/- 1.5 years) performed two 90-min treadmill runs with intensity
      set at the running speeds that corresponded to either 80% (T1) or 100% (T2)
      ventilatory threshold. LV function was examined echocardiographically pre- and
      post-exercise. RESULTS: The two-factor repeated-measures ANOVA revealed no
      significant (P>0.05) main effects for the intensity and the interaction of
      intensityI pre- and postexercise in ejection fraction (EF), systolic blood
      pressure/end systolic volume ratio (SBP/ESV) and early to atrial diastolic flow
      velocity ratio (E:A). Nevertheless, the main effect for time course in EF was
      significant (P<0.05). Pre-exercise EF in T1 (74 +/- 5 vs. 70 +/- 5%, P<0.05), but
      not in T2 (75 +/- 4 vs. 72 +/- 7%, P>0.05), decreased significantly post
      exercise, yet this did not reach clinical levels. Further, no difference (P>0.05)
      was found between pre- and post-exercise in SBP/ESV (T1: 3.9 +/- 0.9 vs. 3.7 +/-
      1.1; T2: 4.0 +/- 0.7 vs. 4.6 +/- 1.9 mmHg.ml-1) and E:A (T1: 1.87 +/- 0.11 vs.
      1.87 +/- 0.11; T2: 1.83 +/- 0.11 vs. 1.87 +/- 0.09) in both trials. CONCLUSION:
      These findings suggest that the training intensities adopted in routine long
      distance run training in the adolescent runners do not seem to induce cardiac
      fatigue. Adolescent hearts appear to cope well with prolonged run performed on
      training.

PMID- 24445551
TI  - Aerobic power and muscle strength of individuals living with HIV/AIDS.
AB  - AIM: We wished to evaluate any continuing adverse effects upon peak aerobic power
      and muscle strength associated with either HAART therapy or persistently low CD4+
      counts in men living with HIV/AIDS. METHODS: We studied 39 HIV/AIDS patients with
      an average disease history of 6.1 years, and 28 normal sedentary volunteers. All
      subjects performed tests of peak aerobic power and isokinetic muscle force, and
      the HIV/AIDS group also completed the Profile of Mood States (POMS) and WHO
      Quality of Life questionnaires. Blood was sampled for standard measures of immune
      function (CD4+ and CD8+ counts) and viral load. RESULTS: Patient values were
      generally as in the normal subjects and appeared to be uninfluenced by the CD4+
      nadir or the use of HAART therapy. However, the isokinetic muscle strength was
      lower in individuals with a low current CD4+ count. Isokinetic strength was also
      negatively correlated with current CD4+ and CD8+ counts. CONCLUSION: HAART
      therapy does not appear to have an adverse long-term effect on either aerobic
      power or muscle strength. Many ambulatory volunteers living with HIV/AIDS have a
      normal peak aerobic power. However, isokinetic strength can remain low,
      particularly in those with low current T-cell counts.

PMID- 24445552
TI  - A reliable unipedal stance test for the assessment of balance using a force
      platform.
AB  - BACKGROUND: The aim was to develop a unipedal stance test for the assessment of
      balance using a force platform. METHODS: A single-leg balance test was conducted
      in 23 students (mean +/- SD) age: 23 +/- 3 years) in a standard position limiting
      the movement of the arms and non-supporting leg. Six attempts, with both the
      jumping (JL) and the contralateral leg (CL), were performed under 3 conditions:
      1) eyes opened; 2) eyes closed; 3) eyes opened and executing a precision task.
      The same protocol was repeated two-week apart. RESULTS: The mean and the best
      result of the six attempts performed each day were taken as representative of
      balance. The speed of the centre of pressure (CP-Speed) showed excellent
      reliability for the "best result" analysis in all tests (ICCs 0.87-0.97), except
      in the test with the eyes closed performed on the CL (ICC<0.4). The CP-Speed had
      better reliability with the "best result" than with the "mean result" analysis
      (P<0.05), whilst no significant differences were observed between the JL and the
      CL (P=0.71 and P=0.96 for mean and best results analysis, respectively). A lower
      dispersion in the Bland and Altman graph was observed with the eyes opened than
      closed, and the dynamic test. CONCLUSION: The single-leg stance balance test
      proposed is a reliable method to assess balance, especially when performed in a
      static position, with the eyes opened and using the best result of six attempts
      as reference, independently of the stance leg.

PMID- 24445553
TI  - A pre-post performance comparison of the long head of the biceps brachii muscle
      oxygenation in young baseball pitchers.
AB  - AIM: The role of the long head of the biceps brachii (LHBB) is vital in
      maintaining stability of the glenohumeral joint during baseball pitching.
      Unfortunately the impact of extended pitching on the ability of the LHBB to
      maintain its function is not currently known. Thus, the purpose of this study was
      to examine the magnitude of muscle oxyhemoglobin saturation in the biceps
      brachii, indicated as tissue saturation index (TSI%), before and following an
      extended pitching performance. METHODS: Data describing the magnitude of TSI% in
      the long head of the biceps brachii (LHBB) were collected from 20 pitchers (12.5
      +/- 2.1 years; 151.2 +/- 11 cm; 46.7 +/- 11.4 kg). TSI% was determined using a
      wireless muscle oximeter based on near-infrared spectroscopy (NIRS). The oximeter
      utilized in this study measured oxy, de-oxy, and total hemoglobin as well as
      tissue saturation. RESULTS: Results revealed that at the conclusion of the
      simulated game, participants experienced an 11.8% decrease in TSI% at contraction
      onset (P<0.05), a 5.9% decrease in TSI% at contraction offset (P<0.05), but no
      difference in TSI% utilized throughout the 5 s isometric contraction.
      Participants demonstrated a 5.9% decrease in change score for TSI% following the
      conclusion of the simulated game which did not differ significantly when compared
      to the beginning of the simulated game (P>0.05). CONCLUSION: These results
      indicate that young pitchers are not at risk of decreased LHBB function due to
      lower TSI%. However, the observation of significantly lower levels associated
      with TSI% following the simulated game reveal that further study into these
      parameters is warranted in older pitchers as they commonly throw greater than 85
      pitches.

PMID- 24445554
TI  - Determining activity energy expenditure from heart rate and physiological
      characteristics.

PMID- 24445555
TI  - Contemporary lymphadenectomy templates: kidney, prostate and bladder cancer.
AB  - PURPOSE OF REVIEW: Lymph node dissection (LDN) at the time of a primary malignant
      resection varies in therapeutic and staging outcomes between organs of origin.
      The purpose of our review is to provide new updates and a key summary on the
      developments in lymphadenectomy templates in kidney, prostate and bladder cancer.
      RECENT FINDINGS: There are still evolving definitions for LDN templates, means of
      pathologic diagnosis of lymph nodes, as well as implications on staging/cancer
      free survival after LND though trends are still emerging. SUMMARY: Routine
      lymphadenectomy does not appear to yield benefit in kidney cancer but maybe
      helpful in those with grossly identifiable disease. For high-risk prostate cancer
      as well as bladder cancer, extended lymphadenectomy with resection of external
      and internal iliac and obturator nodes as well as some common iliac nodes can
      yield survival benefit.

PMID- 24445556
TI  - Postpercutaneous nephrolithotomy bleeding: aetiology and management.
AB  - PURPOSE OF REVIEW: Postpercutaneous nephrolithotomy (PCNL) bleeding is the most
      dreaded complication following PCNL. In this article, we refer to risk factors
      contributing to post-PCNL bleeding and the criteria to decide the line of
      management in such cases. We further discuss the treatment algorithm for the
      management of the complication. RECENT FINDINGS: A perfect puncture is a 'key' to
      avoid post-PNL bleeding. Superselective angioembolization (SAE) is an efficacious
      and well tolerated method of controlling post-PCNL bleeding, and the success rate
      of SAE is found to be greater than 80%. Pseudoaneurysm is the commonest finding
      of SAE, which is responsible for post-PCNL bleeding. A recent study suggested
      that multiple percutaneous accesses, more than two bleeding sites identified
      during renal angiography, and the use of gelatine sponge alone as the embolic
      material were high-risk factors for the failure of SAE. A significant number of
      patients experience postinfarction syndrome in varying degree of severity after
      SAE. SUMMARY: Post-PCNL bleeding is a life-threatening complication. Most of the
      post-PCNL bleeds subside with conservative management, and SAE is an effective
      means of controlling post-PCNL bleeding. A skilled interventionist can achieve
      successful control of bleeding with a variety of agents available. Multiple
      punctures and evidence of more than two lesions predict high risk of failure of
      SAE.

PMID- 24445557
TI  - Laparoscopic and robotic postchemotherapy retroperitoneal lymph node dissection.
AB  - PURPOSE OF REVIEW: Open surgical postchemotherapy retroperitoneal lymph node
      dissection remains the standard of care. On the contrary, laparoscopy is an
      emerging technique and reports of laparoscopic lymph node dissection
      postchemotherapy are increasing. Our purpose is to present indications, technique
      and outcomes of laparoscopic postchemo retroperitoneal lymph node dissection.
      RECENT FINDINGS: With growing expertise and knowledge the morbidity of the
      laparoscopic approach is much reduced compared with open surgery with the same
      oncological outcome. Robotic surgery is a more recent approach with growing usage
      in urology. However, no reports of robotic postchemotherapy lymph node dissection
      are available. SUMMARY: In expert hands laparoscopic lymph node dissection is a
      feasible technique, offering less morbidity to patients with good oncological
      results.

PMID- 24445558
TI  - Vitamin D as an early predictor of multiple sclerosis activity and progression.
AB  - IMPORTANCE: It remains unclear whether vitamin D insufficiency, which is common
      in individuals with multiple sclerosis (MS), has an adverse effect on MS
      outcomes. OBJECTIVES: To determine whether serum concentrations of 25
      hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease
      activity and prognosis in patients with a first event suggestive of MS
      (clinically isolated syndrome). DESIGN, SETTING, AND PARTICIPANTS: The
      Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment
      study was a randomized trial originally designed to evaluate the impact of early
      vs delayed interferon beta-1b treatment in patients with clinically isolated
      syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and
      24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D
      measurement, and 334 patients had them at both the 6- and 12-month (seasonally
      asynchronous) measurements. Patients were followed up for 5 years clinically and
      by magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: New active lesions,
      increased T2 lesion volume, and brain volume on magnetic resonance imaging, as
      well as MS relapses and disability (Expanded Disability Status Scale score).
      RESULTS: Higher 25(OH)D levels predicted reduced MS activity and a slower rate of
      progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels
      within the first 12 months predicted a 57% lower rate of new active lesions (P <
      .001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion
      volume (P < .001), and 0.41% lower yearly loss in brain volume (P = .07) from
      months 12 to 60. Similar associations were found between 25(OH)D measured up to
      12 months and MS activity or progression from months 24 to 60. In analyses using
      dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL)
      at up to 12 months predicted lower disability (Expanded Disability Status Scale
      score, -0.17; P = .004) during the subsequent 4 years. CONCLUSIONS AND RELEVANCE:
      Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels
      early in the disease course are a strong risk factor for long-term MS activity
      and progression.

PMID- 24445559
TI  - Long-term changes in renal function outcomes following radical cystectomy and
      urinary diversion.
AB  - BACKGROUND: We analyzed long-term changes in the renal function of patients
      undergoing radical cystectomy and urinary diversion (UD). METHODS: This study
      included 169 patients who underwent radical cystectomy and UD (42, cutaneous
      ureterostomy; 40, ileal conduit; 87, neobladder substitution), and were followed
      for at least 60 months (median 106 months). Renal deterioration was defined as a
      >25 % decrease in the estimated glomerular filtration rate (eGFR) relative to
      that prior to surgery. We determined the associations between several parameters
      and postoperative renal deterioration. RESULTS: Despite the significantly younger
      age and more favorable renal function of patients with neobladder substitution
      than of those with other types of UD, no significant differences were observed in
      the remaining preoperative clinical parameters among the three different UD
      groups. The mean eGFR of the 169 patients decreased from 69.6 to 55.9 mL/min/1.73
      m(2), and renal deterioration was observed in 24 (57.1 %), 20 (50.0 %) and 34
      (39.0 %) patients in the cutaneous ureterostomy, ileal conduit and neobladder
      substitution groups, respectively. Multivariate analysis of several parameters
      identified the presence of baseline hypertension and an episode of acute
      pyelonephritis, but not the type of UD, as significant predictors of
      postoperative renal deterioration. CONCLUSIONS: The incidence of renal
      deterioration was comparatively high following radical cystectomy, irrespective
      of the type of UD. Special attention should be paid to the long-term preservation
      of renal function in these patients, particularly those with hypertension and/or
      episodes of acute pyelonephritis.

PMID- 24445560
TI  - Methadone patient-controlled analgesia for postoperative pain: a randomized,
      controlled, double-blind study.
AB  - PURPOSE: Postoperative pain is an important health-care issue. Patient-controlled
      analgesia (PCA) is considered the gold standard for systemic postoperative pain
      treatment. Methadone PCA is used for patients with chronic pain and those in the
      palliative care setting. However, its efficacy as a first-line drug for acute
      postoperative pain is unknown. This study evaluated the use of postoperative
      methadone PCA after total hip arthroplasty (THA) compared with morphine PCA.
      METHODS: This was a randomized, double-blind, controlled, parallel-group study.
      Patients were randomized into two groups: group methadone--methadone PCA, and
      group morphine--morphine PCA, for postoperative analgesia. Drugs were delivered
      through PCA pumps throughout the first 24 h after surgery (T1:6, T2:12, T3:18,
      T4:24 h). RESULTS: Opioid consumption in 24 h was significantly lower for group
      methadone than for group morphine. Group methadone patients experienced
      significantly less pain than group morphine at rest. Pain after movement was
      significantly lower in group methadone at T1 and T3 and marginally lower at T2
      and T4. Adverse events more frequently reported were sleepiness, nausea, and
      vomiting, but no statistical difference between groups was found. CONCLUSION:
      This study demonstrated that methadone PCA prompted less opioid consumption and
      lower pain scores at rest and at motion in comparison with morphine PCA as
      postoperative analgesia after THA.

PMID- 24445562
TI  - Biosimilar competition: lessons from Europe.

PMID- 24445564
TI  - Nickel-catalyzed cross-coupling of aryltrimethylammonium triflates and amines.
AB  - Nickel-catalyzed cross-coupling of aryltrimethylammonium triflates and amines was
      carried out under mild conditions. The reaction has a broad scope of substrates
      and can be performed by a one-pot procedure from an aryldimethylamine. 

PMID- 24445565
TI  - Metastatic involvement of the pituitary gland: a systematic review with pooled
      individual patient data analysis.
AB  - PURPOSE: To report a rare case of pituitary metastasis (PM) from hepatocellular
      carcinoma (HCC) and help better understand the incidence of PM and its most
      common presenting symptoms through a pooled individual patient data analysis.
      METHODS: Literature regarding PM was systematically reviewed with a pooled
      individual patient data analysis conducted. Pooled individual data analysis
      result is also compared with the result in a most recent systematic review.
      RESULTS: Our results demonstrate that the incidence of PM among all intracranial
      metastases is 0.87% (95% CI 0.56, 1.18); it is 1.9% (95% CI 1.46, 2.34) among all
      autopsied cancer cases; it is 11.56% (95% CI 7.08, 16.04) among all breast cancer
      patients who had hypophysectomies and 12.83% (95% CI 10.5, 15.16) among all
      autopsied breast cancer patients. The fixed effect model showed that the
      incidence of PM in breast cancer patients group is significantly higher (p <
      0.001) with an odds ratio of 6.71 (95% CI 4.24, 10.61). Breast and lung cancer
      are the most common primary cancer of PM with a percentage of 37.2 and 24.2
      respectively. The next most common primary sites are prostate and kidney
      respectively, although the percentages for each are only about 5. Diabetes
      insipidus (DI) remains the most common symptom among all reported PM cases with a
      pooled incidence of 42.34% (95% CI 36.15, 48.53). Although not significant
      (chi(2) = 2.846, df = 1, p = 0.061), it is less common in the most recent
      reported cases which has a pooled incidence of 32.76% (95% CI 20.31, 45.21). DI
      is extremely rare in the reported PM cases from HCC (none of the eight cases
      presented with DI). The symptoms of anterior hypopituitarism (23.68 vs 39.66%, p
      = 0.015), visual deterioration (27.89 vs 41.38%, p = 0.039), cranial nerve
      palsies (21.58 vs 41.38%, p = 0.003) and headaches (15.79 vs 32.76%, p = 0.005)
      were reported significantly higher than previously described in the literature.
      CONCLUSIONS: Pituitary metastasis is rare in patients with cancer, and the
      pituitary gland is an uncommonly involved location in patients with intracranial
      metastases. With advanced diagnostic imaging techniques and increased awareness
      about the manifestation of sellar lesions, the incidence of cranial nerve palsies
      and anterior pituitarism are higher than reported. This information may allow
      earlier diagnosis of PM.

PMID- 24445566
TI  - Long-term impact of the 70-gene signature on breast cancer outcome.
AB  - Several studies have validated the prognostic value of the 70-gene prognosis
      signature (MammaPrint(R)), but long-term outcome prediction of these patients has
      not been previously reported. The follow-up of the consecutively treated cohort
      of 295 patients (<53 years) with invasive breast cancer (T1-2N0-1M0; n = 151 N0,
      n = 144 N1) diagnosed between 1984 and 1995, in which the 70-gene signature was
      previously validated, was updated. The median follow-up for this series is now
      extended to 18.5 years. A significant difference is seen in long-term distant
      metastasis-free survival (DMFS) for the patients with a low- and a high-risk 70
      gene signature (DMFS p < 0.0001), as well as separately for node-negative (DMFS p
      < 0.0001) and node-positive patients (DMFS p = 0.0004). The 25-year hazard ratios
      (HRs) for all patients for DMFS and OS were 3.1 (95 % CI 2.02-4.86) and 2.9 (95 %
      CI 1.90-4.28), respectively. The HRs for DMFS and OS were largest in the first 5
      years after diagnosis: 9.6 (95 % CI 4.2-22.1) and 11.3 (95 % CI 3.5-36.4),
      respectively. The 25-year HRs in the subgroup of node-negative patients for DMFS
      and OS were 4.57 (95 % CI 2.31-9.04) and 4.73 (95 % CI 2.46-9.07), respectively,
      and for node-positive patients for DMFS and OS were 2.24 (95 % CI 1.25-4.00) and
      1.83 (95 % CI 1.07-3.11), respectively. The 70-gene signature remains prognostic
      at longer follow-up in patients <53 years of age with stage I and II breast
      cancer. The 70-gene signature's strongest prognostic power is seen in the first 5
      years after diagnosis.

PMID- 24445563
TI  - Herpesvirus-encoded GPCRs: neglected players in inflammatory and proliferative
      diseases?
AB  - Herpesviruses encode membrane-associated G protein-coupled receptors (GPCRs) in
      their viral genomes that are structurally similar to chemokine receptors. These
      GPCRs hijack GPCR-mediated cellular signalling networks of the host for survival,
      replication and pathogenesis. In particular the herpesvirus-encoded chemokine
      receptors ORF74, BILF1 and US28, which are present at inflammatory sites and
      tumour cells, provide important virus-specific targets for directed therapies.
      Given the high druggability of GPCRs in general, these viral GPCRs can be
      considered promising antiviral drug targets. 

PMID- 24445567
TI  - Mortality and Productivity Losses From Alzheimer Disease Among US Adults Aged 40
      to 64 Years, 1999 to 2010.

PMID- 24445568
TI  - Gastrointestinal effects of eating quinoa (Chenopodium quinoa Willd.) in celiac
      patients.
AB  - OBJECTIVES: Celiac disease is an enteropathy triggered by dietary gluten found in
      wheat, rye, and barley. Treatment involves a strict gluten-free diet (GFD).
      Quinoa is a highly nutritive plant from the Andes that has been recommended as
      part of a GFD. However, in-vitro data suggested that quinoa prolamins can
      stimulate innate and adaptive immune responses in celiac patients. Therefore, we
      aimed to evaluate the in-vivo effects of eating quinoa in adult celiac patients.
      METHODS: Nineteen treated celiac patients consumed 50 g of quinoa every day for 6
      weeks as part of their usual GFD. We evaluated diet, serology, and
      gastrointestinal parameters. Furthermore, we carried out detail histological
      assessment of 10 patients before and after eating quinoa. RESULTS:
      Gastrointestinal parameters were normal. The ratio of villus height to crypt
      depth improved from slightly below normal values (2.8:1) to normal levels (3:1),
      surface-enterocyte cell height improved from 28.76 to 29.77 MUm and the number of
      intra-epithelial lymphocytes per 100 enterocytes decreased from 30.3 to 29.7.
      Median values for all the blood tests remained within normal ranges, although
      total cholesterol (n=19) decreased from 4.6 to 4.3 mmol/l, low-density
      lipoprotein decreased from 2.46 to 2.45 mmol/l, high-density lipoprotein
      decreased from 1.8 to 1.68 mmol/l and triglycerides decreased from 0.80 to 0.79
      mmol/l. CONCLUSIONS: Addition of quinoa to the GFD of celiac patients was well
      tolerated and did not exacerbate the condition. There was a positive trend toward
      improved histological and serological parameters, particularly a mild
      hypocholesterolemic effect. Overall, this is the first clinical data suggesting
      that daily 50 g of quinoa for 6 weeks can be safely tolerated by celiac patients.
      However, further studies are needed to determine the long-term effects of quinoa
      consumption.

PMID- 24445569
TI  - The optimal number of biopsy fragments to establish a morphologic diagnosis of
      eosinophilic esophagitis.
AB  - OBJECTIVES: Eosinophilic esophagitis (EoE) is characterized clinically by
      dysphagia, chest pain, and food impaction, and morphologically by increased
      numbers of intraepithelial eosinophils and marked basal hyperplasia of the
      squamous mucosa. The consensus criteria for a diagnosis of EoE include the
      presence of >=15 eosinophils/HPF in biopsies from both proximal and distal
      esophagus in the absence of other causes of esophageal eosinophilia, and the lack
      of clinical response to proton pump inhibitor therapy. Because of the variability
      in the distribution of intraepithelial eosinophils among biopsy fragments and the
      lack of standardized biopsy practices, we sought to determine the optimal number
      of esophageal biopsies from the mid and distal esophagus needed to reach the
      minimum morphologic criteria of >=15 eosinophils/HPF. METHODS: From 5 January
      2009 to 26 September 2011, 771 patients were diagnosed with EoE at our
      institution. From that patient population, 102 sequential cases were chosen for
      further study, all of whom had biopsies taken from the mid and distal esophagus.
      Cases with only gastric mucosa present and biopsies taken from patients with a
      previous diagnosis of EoE were excluded. The original H&E-stained slides were
      reviewed, and the number of biopsy fragments containing squamous mucosa was
      recorded. By using a * 40 objective and * 10 oculars (field diameter=0.52 mm,
      field area=0.21 mm(2)), the number of eosinophils per high power field (EOS/HPF)
      in up to three HPFs was counted in each biopsy fragment. RESULTS: The EOS/HPF
      were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained
      from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained
      from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no
      significant difference between the mean number of EOS/HPF from the mid (26) and
      lower (25) esophagus or between the mean peak number of EOS/HPF from the mid
      (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six
      biopsy fragments containing >15 EOS/HPF was 0.63, 0.98, 0.99, and >0.99,
      respectively. CONCLUSIONS: From these data, at least four biopsy fragments should
      be submitted from the mid and/or proximal esophagus to optimize the chances of a
      positive diagnosis of EoE in populations not known to have undergone previous
      proton pump inhibitor therapy. However, the yield is not increased beyond six
      biopsy fragments. In order to morphologically exclude a diagnosis of reflux
      esophagitis as the cause of intraepithelial eosinophilia, distal esophageal
      biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid
      esophagus or higher).

PMID- 24445570
TI  - The contribution of viral hepatitis to the burden of chronic liver disease in the
      United States.
AB  - OBJECTIVES: Chronic liver disease (CLD) is increasingly recognized as a major
      public health problem. However, in the United States, there are few nationally
      representative data on the contribution of viral hepatitis as an etiology of CLD.
      METHODS: We applied a previously used International Classification of Diseases,
      Ninth Revision, Clinical Modification-based definition of CLD cases to the
      National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical
      Care Survey databases for 2006-2010. We estimated the mean number of CLD visits
      per year, prevalence ratio of visits by patient characteristics, and the
      percentage of CLD visits attributed to viral hepatitis and other selected
      etiologies. RESULTS: An estimated 6.0 billion ambulatory care visits occurred in
      the United States from 2006 to 2010, of which an estimated 25.8 million (0.43%)
      were CLD-related. Among adults aged 45-64 years, Medicaid and Medicare recipients
      were 3.9 (prevalence ratio (PR)=3.9, 95% confidence limit (CL; 2.8, 5.4)) and 2.3
      (PR=2.3, 95% CL (1.6, 3.4)) times more likely to have a CLD-related ambulatory
      visit than those with private insurance, respectively. In the United States, from
      2006 to 2010, an estimated 49.6% of all CLD-related ambulatory visits were
      attributed solely to viral hepatitis B and C diagnoses. CONCLUSIONS: In this
      unique application of health-care utilization data, we confirm that viral
      hepatitis is an important etiology of CLD in the United States, with hepatitis B
      and C contributing approximately one-half of the CLD burden. CLD ambulatory
      visits in the United States disproportionately occur among adults, aged 45-64
      years, who are primarily minorities, men, and Medicare or Medicaid recipients.

PMID- 24445571
TI  - Host and viral determinants of the outcome of exposure to HCV infection genotype
      4: a large longitudinal study.
AB  - OBJECTIVES: The objective of this study was to characterize the factors that
      influence the outcome of exposure to hepatitis C virus (HCV) genotype 4 (HCV-G4)
      and the course of recent infection. METHODS: In this longitudinal study, we
      prospectively assessed the clinical, genetic, virological, and immunological
      parameters and retrospectively determined single-nucleotide polymorphisms at
      interleukin-28B (IL-28B) rs12979860 in a well-characterized large cohort recently
      exposed to HCV-G4. RESULTS: A total of 136 subjects with acute HCV (new viremia,
      seroconversion, and HCV-specific T-cell responses) were identified. Forty-eight
      subjects (35%) had spontaneous viral clearance and 88 subjects developed chronic
      HCV of which 42 subjects were treated with pegylated interferon monotherapy, with
      a sustained virologic response (SVR) rate of 88%. Twenty-six subjects developed
      HCV-specific T-cell immune responses without detectable viremia or
      seroconversion. IL-28B-CC (odds ratio (OR) 14.22; P<0.0001), multispecific T-cell
      responses (OR=11.66; P<0.0001), >300 IU/l alanine aminotransferase (ALT) decline
      within 4 weeks (OR=6.83; P<0.0001), jaundice (OR=3.54; P=0.001), female gender
      (OR=2.39; P=0.007), and >2.5 log10 HCV-RNA drop within 8 weeks (OR=2.48; P=0.016)
      were independently associated with spontaneous clearance. ALT normalization and
      undetectable HCV-RNA predicted SVR. Exposed apparently uninfected participants
      had a higher frequency of IL-28B-CC than patients with unresolved acute HCV
      (P<0.001). IL-28B-CC was associated with multispecific T-cell response
      (r(2)=0.0.835; P<0.001). CONCLUSIONS: IL-28B-CC genotype, multispecific HCV T
      cell responses, rapid decline in ALT, and viral load predict spontaneous
      clearance and response to acute HCV-G 4 therapy. IL-28B-CC genotype correlates
      with developing early multispecific T-cell responses. These findings have
      important implications for predicting the outcome of HCV exposure and acute
      infection and identifying patients likely to benefit from therapy.

PMID- 24445572
TI  - Validation of a CT-derived method for osteoporosis screening in IBD patients
      undergoing contrast-enhanced CT enterography.
AB  - OBJECTIVES: Osteoporosis and bone fractures are of particular concern in patients
      with inflammatory bowel disease (IBD). Biomechanical computed tomography (BCT) is
      an image-analysis technique that can measure bone strength and dual-energy X-ray
      absorptiometry (DXA)-equivalent bone mineral density (BMD) from noncontrast CT
      images. This study seeks to determine whether this advanced technology can be
      applied to patients with IBD undergoing CT enterography (CTE) with IV contrast.
      METHODS: Patients with IBD who underwent a CTE and DXA scan between 2007 and 2011
      were retrospectively identified. Femoral neck BMD (g/cm(2)) and T-scores were
      measured and compared between DXA and BCT analysis of the CTE images. Femoral
      strength (Newtons) was also determined from BCT analysis. RESULTS: DXA- and CTE
      generated BMD T-score values were highly correlated (R(2)=0.84, P<0.0001) in this
      patient cohort (n=136). CTE identified patients with both osteoporosis
      (sensitivity, 85.7%; 95% confidence interval (CI), 48.7-97.4 and specificity,
      98.5%; 95% CI, 94.5-99.6) and osteopenia (sensitivity, 85.1%; 95% CI, 72.3-92.6
      and specificity, 85.4%; 95% CI, 76.6-91.3). Of the 16 patients who had "fragile"
      bone strength by BCT (placing them at the equivalent high risk of fracture as for
      osteoporosis), 6 had osteoporosis and 10 had osteopenia by DXA. CONCLUSIONS: CTE
      scans can provide hip BMD, T-scores, and clinical classifications that are
      comparable to those obtained from DXA; when combined with BCT analysis, CTE can
      identify a subset of patients with osteopenia who have clinically relevant
      fragile bone strength. This technique could markedly increase bone health
      assessments in IBD patients already undergoing CTE to evaluate small bowel
      disease.

PMID- 24445573
TI  - Psychosocial characteristics and pain burden of patients with suspected sphincter
      of Oddi dysfunction in the EPISOD multicenter trial.
AB  - OBJECTIVES: Patients with several painful functional gastrointestinal disorders
      (FGIDs) are reported to have a high prevalence of psychosocial disturbance. These
      aspects have not been studied extensively in patients with suspected Sphincter of
      Oddi dysfunction (SOD). METHODS: A total of 214 patients with post
      cholecystectomy pain and suspected SOD were enrolled in seven US centers in a
      multicenter-randomized trial (Evaluating Predictors and Interventions in
      Sphincter of Oddi Dysfunction). Baseline assessments included pain descriptors
      and burden, structured psychosocial assessments of anxiety/depression, coping,
      trauma, and health-related quality of life. Patients with high levels of
      depression, suicidal ideation, or psychosis were excluded. RESULTS: The study
      population (92% female, mean age 38) reported anxiety (9%), depression (8%), past
      sexual trauma (18%), and physical abuse (10%). Of the total screened population
      (n=1460), 3.9% of the patients were excluded because of the presence of defined
      severe psychological problems. The mean medical outcomes study short-form-36 (SF
      36) physical and mental composite scores were 38.70 (s.d.=7.89) and 48.74
      (s.d.=9.60), respectively. Most subjects reported symptoms of other FGIDs. There
      were no correlations between the extent of the pain burden in the 3 months before
      enrollment and the baseline anxiety scores or victimization history. However,
      those with greater pain burden were significantly more depressed. There were no
      meaningful differences in the psychosocial parameters in subjects with or without
      irritable bowel, and those who had cholecystectomy for stones or functional
      gallbladder disease. Those declining randomization were comparable to those
      randomized. CONCLUSIONS: Psychosocial comorbidity in SOD is high. However, it
      does not appear to differ significantly from that reported in surveys of age- and
      gender-matched general populations, and may be lower than reported with other
      FGIDs.

PMID- 24445574
TI  - The effect of PNPLA3 on fibrosis progression and development of hepatocellular
      carcinoma: a meta-analysis.
AB  - OBJECTIVES: The PNPLA3 rs738409 single-nucleotide polymorphism is known to
      promote nonalcoholic steatohepatitis (NASH), but its association with fibrosis
      severity and hepatocellular carcinoma (HCC) risk is less well-defined. The
      objectives of this study were to determine the association between PNPLA3 and
      liver fibrosis severity, HCC risk, and HCC prognosis among patients with liver
      disease. METHODS: We performed a systematic literature review using the Medline,
      PubMed, Scopus, and Embase databases through May 2013 and a manual search of
      national meeting abstracts from 2010 to 2012. Two investigators independently
      extracted data on patient populations, study methods, and results using
      standardized forms. Pooled odds ratios (ORs), according to PNPLA3 genotype, were
      calculated using the DerSimonian and Laird method for a random effects model.
      RESULTS: Among 24 studies, with 9,915 patients, PNPLA3 was associated with
      fibrosis severity (OR 1.32, 95% confidence interval (CI) 1.20-1.45), with a
      consistent increased risk across liver disease etiologies. Among nine studies,
      with 2,937 patients, PNPLA3 was associated with increased risk of HCC in patients
      with cirrhosis (OR 1.40, 95% CI 1.12-1.75). On subgroup analysis, increased risk
      of HCC was demonstrated in patients with NASH or alcohol-related cirrhosis (OR
      1.67, 95% CI 1.27-2.21) but not in those with other etiologies of cirrhosis (OR
      1.33, 95% CI 0.96-1.82). Three studies, with 463 patients, do not support an
      association between PNPLA3 and HCC prognosis but are limited by heterogeneous
      outcome measures. For all outcomes, most studies were conducted in homogenous
      Caucasian populations, and studies among racially diverse cohorts are needed.
      CONCLUSIONS: PNPLA3 is associated with an increased risk of advanced fibrosis
      among patients with a variety of liver diseases and is an independent risk factor
      for HCC among patients with nonalcoholic steatohepatitis or alcohol-related
      cirrhosis.

PMID- 24445576
TI  - Internal iliac and uterine arteries Doppler ultrasound in the assessment of
      normotensive and chronic hypertensive pregnant women.
AB  - The objective of this work was to compare Doppler flows pulsatility index (PI)
      and resistance indexes (RI) of uterine and internal iliac arteries during
      pregnancy in low risk women and in those with stage-1 essential hypertension.
      From January 2010 and December 2012, a longitudinal and prospective study was
      carried out in 103 singleton uneventful pregnancies (72 low-risk pregnancies and
      31 with stage 1 essential hypertension)at the 1(st), 2(nd) and 3(rd) trimesters.
      Multiple linear regression models, fitted using generalized least squares and
      whose errors were allowed to be correlated and/or have unequal variances, were
      employed; a model for the relative differences of both arteries impedance was
      utilized. In both groups, uterine artery PI and RI exhibited a gestational age
      related decreasing trend whereas internal iliac artery PI and RI increased. The
      model testing the hemodynamic adaptation in women with and without hypertension
      showed similar trend. Irrespective of blood pressure conditions, the internal
      iliac artery resistance pattern contrasts with the capacitance pattern of its
      immediate pelvic division, suggesting a pregnancy-related regulatory mechanism in
      the pelvic circulation. 

PMID- 24445575
TI  - TRPA1 channels mediate acute neurogenic inflammation and pain produced by
      bacterial endotoxins.
AB  - Gram-negative bacterial infections are accompanied by inflammation and somatic or
      visceral pain. These symptoms are generally attributed to sensitization of
      nociceptors by inflammatory mediators released by immune cells. Nociceptor
      sensitization during inflammation occurs through activation of the Toll-like
      receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by
      product of bacterial lysis. Here we show that LPS exerts fast, membrane
      delimited, excitatory actions via TRPA1, a transient receptor potential cation
      channel that is critical for transducing environmental irritant stimuli into
      nociceptor activity. Moreover, we find that pain and acute vascular reactions,
      including neurogenic inflammation (CGRP release) caused by LPS are primarily
      dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop
      independently of TLR4 activation. The identification of TRPA1 as a molecular
      determinant of direct LPS effects on nociceptors offers new insights into the
      pathogenesis of pain and neurovascular responses during bacterial infections and
      opens novel avenues for their treatment. 

PMID- 24445577
TI  - Detection of the edible ectomycorrhizal fungus Lyophyllum shimeji colonising
      seedlings of cultivated conifer species in New Zealand.
AB  - Lyophyllum shimeji is an edible ectomycorrhizal fungus that is widely distributed
      in East Asia and also present in the northern regions of Europe. In Japan, L.
      shimeji is a culinary delicacy, considered amongst all edible mushrooms to have
      the best taste and to be second only to Tricholoma matsutake in price.
      Traditionally, fruiting bodies of L. shimeji have been collected from the wild
      but fruiting of L. shimeji is now relatively uncommon and cannot keep up with
      increasing consumer demand. As a result, methods for its cultivation are being
      developed for commercial production in Japan and other countries. In this work,
      techniques were developed to cultivate L. shimeji on coniferous seedlings using a
      pure culture inoculum. They resulted in successful mycorrhization of Pinus
      pinaster and Picea abies in only 8 to 10 months. As ectomycorrhizae of L. shimeji
      are difficult to identify morphologically, mycorrhization was confirmed using an
      L. shimeji-specific PCR diagnostic, which was designed following a phylogenetic
      analysis of the Lyophyllum section Difformia using DNA sequences of the internal
      transcribed spacer (ITS), intergenic spacer (IGS) and elongation factor 1-alpha
      (EF1-alpha) gene. L. shimeji is a member of the Lyophyllum decastes complex in
      section Difformia, which also includes Lyophyllum fumosum and L. decastes. This
      analysis confirmed the separation of L. shimeji from closely related Lyophyllum
      spp. and enabled its unambiguous detection using an IGS-based PCR diagnostic.
      This is the first report of successful mycorrhization of L. shimeji on P.
      pinaster and P. abies and provides an opportunity for its commercial cultivation
      on conifers in New Zealand.

PMID- 24445578
TI  - Short-term effects of the 2008 Great Recession on the health of the Italian
      population: an ecological study.
AB  - PURPOSE: To report on the effects on health that the 2008 Great Recession is
      producing in Italy, by comparing the consistency of Italian data with general
      observations reported in the scientific literature, and by pointing out
      consequences on the rates of all-cause mortality, cardiovascular mortality, male
      suicidal behaviours, daytime alcohol drinking and traffic fatalities. METHODS:
      This is an ecological study in which MEDLINE, PsycINFO and PubMed were searched
      for the literature with combinations of the following keywords: economic
      recession, financial crisis, unemployment, health, suicide and mental health.
      Data from two Italian government agencies (Italian Institute of Statistics,
      ISTAT, and Italian Agency of Drugs, AIFA) in the years from 2000 to 2010 were
      obtained and analysed, by producing models of multiple linear regressions.
      RESULTS: After the recession onset, all-cause mortality remained stable, and was
      not associated with the economic fluctuations. Differently, cardiovascular
      mortality was associated with the rate of unemployment, and showed a significant
      increase in 2010. Alcohol consumption increased in 2009, the year with the worst
      real GDP decrease (-5.1 %). Though the total rate of suicide was not associated
      with the economic situation, male completed and attempted suicides due to
      financial crisis were significantly associated with the rate of unemployment and
      the real GDP. The increasing diffusion of antidepressants was not associated with
      a lowering of the rate of suicide. CONCLUSIONS: The data on the Italian situation
      here discussed are sufficiently reliable to conclude that a link exists between
      the ongoing economic recession and health and mental health of Italians. Further
      research is needed to understand more in detail and with stronger reliability
      such link, to support primary and secondary preventive interventions and orient
      the development of effective sociopolitical interventions.

PMID- 24445579
TI  - The co-occurrence of PTSD and dissociation: differentiating severe PTSD from
      dissociative-PTSD.
AB  - PURPOSE: A dissociative-posttraumatic stress disorder (PTSD) subtype has been
      included in the DSM-5. However, it is not yet clear whether certain socio
      demographic characteristics or psychological/clinical constructs such as comorbid
      psychopathology differentiate between severe PTSD and dissociative-PTSD. The
      current study investigated the existence of a dissociative-PTSD subtype and
      explored whether a number of trauma and clinical covariates could differentiate
      between severe PTSD alone and dissociative-PTSD. METHODS: The current study
      utilized a sample of 432 treatment seeking Canadian military veterans.
      Participants were assessed with the Clinician Administered PTSD Scale (CAPS) and
      self-report measures of traumatic life events, depression, and anxiety. CAPS
      severity scores were created reflecting the sum of the frequency and intensity
      items from each of the 17 PTSD and 3 dissociation items. The CAPS severity scores
      were used as indicators in a latent profile analysis (LPA) to investigate the
      existence of a dissociative-PTSD subtype. Subsequently, several covariates were
      added to the model to explore differences between severe PTSD alone and
      dissociative-PTSD. RESULTS: The LPA identified five classes: one of which
      constituted a severe PTSD group (30.5 %), and one of which constituted a
      dissociative-PTSD group (13.7 %). None of the included, demographic, trauma, or
      clinical covariates were significantly predictive of membership in the
      dissociative-PTSD group compared to the severe PTSD group. CONCLUSIONS: In
      conclusion, a significant proportion of individuals report high levels of
      dissociation alongside their PTSD, which constitutes a dissociative-PTSD subtype.
      Further investigation is needed to identify which factors may increase or
      decrease the likelihood of membership in a dissociative-PTSD subtype group
      compared to a severe PTSD only group.

PMID- 24445580
TI  - Frontotemporal dementia associated with the C9ORF72 mutation: a unique clinical
      profile.
AB  - IMPORTANCE: While advances have been made in characterizing the C9ORF72 clinical
      phenotype, the hallmark features that discriminate between carriers and
      noncarriers remain unclear. OBJECTIVES: To determine the frequency of the C9ORF72
      mutation in a frontotemporal dementia (FTD) cohort and to define the clinical,
      neuropsychological, behavioral, and imaging features of C9ORF72 mutation carriers
      in comparison with noncarriers in a well-defined behavioral-variant (bv)-FTD
      cohort. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of patients
      assessed during a 5-year period from January 1, 2008, to December 31, 2012, at an
      FTD specialist referral center (FRONTIER). A total of 114 consecutive patients
      with FTD, FTD-amyotrophic lateral sclerosis (ALS), and corticobasal syndrome were
      assessed at FRONTIER. Patients with bvFTD who carried the C9ORF72 mutation (n =
      10) were compared with noncarriers (n = 19) and a healthy control group (n = 35).
      These were matched for age, sex, and education history. Blood sampling for gene
      analysis was performed after informed consent was obtained. MAIN OUTCOMES AND
      MEASURES: Clinical, behavioral, cognitive, and neuropsychological deficits,
      cortical atrophy on a magnetic resonance imaging visual rating scale, and family
      history as quantified by the Goldman Scale. RESULTS: In a cohort of 114 FTD
      cases, 14 patients expressed the C9ORF72 mutation, representing a frequency rate
      of 34% in bvFTD and 17% in FTD-ALS. Family histories of ALS (P = .001) and
      psychiatric disorders (P = .02) were significantly more common in mutation
      carriers. The C9ORF72 carriers were also more likely to experience psychotic
      symptoms (P = .03). The degree of brain atrophy was significantly less in the
      C9ORF72 cohort, and in many the progression was slow. Presenting features of
      C9ORF72 carriers were compared against International Consensus Diagnostic
      Criteria for bvFTD, and most cases failed to satisfy criteria for probable bvFTD.
      CONCLUSIONS AND RELEVANCE: The C9ORF72 mutation appears to be a common cause of
      bvFTD. Many of the C9ORF72 carriers have a family history of ALS or psychiatric
      illness. Psychotic features emerged as the most discriminating clinical feature
      between mutation carriers and noncarriers. Progression is often slow and brain
      atrophy is less pronounced than in nonmutation cases of bvFTD. These findings
      have clinical relevance for both diagnosis and selection of patients for genetic
      testing.

PMID- 24445581
TI  - Carbon black anchored vanadium oxide nanobelts and their post-sintering
      counterpart (V2O5 nanobelts) as high performance cathode materials for lithium
      ion batteries.
AB  - Carbon black (CB) anchored vanadium oxide (C-VOx) nanobelts are successfully
      prepared by a simple sol-gel route and subsequent hydrothermal treatment. The
      synthesized C-VOx nanobelts display high specific capacity and good cycling
      stability as a cathode material for lithium ion batteries (LIBs) (232 mA h g(-1)
      at initial discharge and 195 mA h g(-1) during 50th discharge at a current
      density of 100 mA g(-1) between 1.5-4 V versus Li) due to the nano-belted
      morphology and closely attached CB. The orthorhombic V2O5 nanobelts can be
      obtained by post-sintering of C-VOx nanobelts in air. These V2O5 nanobelts, which
      maintain their previous belted morphology and possess higher vanadium valence,
      exhibit superior electrochemical properties, especially the higher specific
      capacity (406 mA h g(-1) and 220 mA h g(-1) during the 1st and 50th discharge at
      a current density of 100 mA g(-1), and 146 mA h g(-1) at a current density of
      1000 mA g(-1) between 1.5-4 V versus Li). Both of them can be used as high
      performance cathode materials for LIB application. Furthermore, a full-cell using
      V2O5 nanobelts as the cathode and lithiated graphite as the anode is assembled
      and its electrochemical performance is measured in the voltage range of 1.5-3.8
      V. 

PMID- 24445586
TI  - Pharmacotherapy: Novel antibody therapy demonstrates potential for building bone
      in osteoporosis.

PMID- 24445587
TI  - The obesity paradox in chronic heart failure: what does it mean?
AB  - Heart failure (HF) is a growing health problem, at least in part due to the
      concurrent obesity epidemic plaguing developed countries. However, once a patient
      develops HF, an elevated BMI appears to confer a survival benefit--a phenomenon
      termed the "obesity paradox." The exact explanation for this paradox has been
      difficult to ascertain. Numerous plausible mechanisms have been asserted,
      including the fact that obese patients tend to be younger and more symptomatic,
      leading them to seek medical attention earlier in the course of their HF. Obese
      patients may also have larger energy reserves that help to offset the catabolic
      changes seen with HF. Other hypotheses highlight the limitations of BMI as an
      obesity classifier. The purpose of this review is to examine the various theories
      for the obesity paradox in HF and discuss the implications for the clinical
      management of obese patients with HF.

PMID- 24445588
TI  - Growth morphology of thin films on  metallic and oxide surfaces.
AB  - In this work we briefly review recent investigations concerning the growth
      morphology of thin metallic films on the Mo(110) and Ni3Al(111) surfaces, and Fe
      and copper phthalocyanine (C32H16N8Cu) on the Al2O3/Ni3Al(111) surface.
      Comparison of Ag, Au, Sn, and Pb growth on the Mo(110) surface has shown a number
      of similarities between these adsorption systems, except that surface alloy
      formation has only been observed in the case of Sn and Au. In the Pb/Mo(110) and
      Pb/Ni3Al(111) adsorption systems selective formation of uniform Pb island heights
      during metal thin film growth has been observed and interpreted in terms of
      quantum size effects. Furthermore, our studies showed that Al2O3 on Ni3Al(111)
      exhibits a large superstructure in which the unit cell has a commensurate
      relation with the substrate lattice. In addition, copper phthalocyanine
      chemisorbed weakly onto an ultra-thin Al2O3 film on Ni3Al(111) and showed a poor
      template effect of the Al2O3/Ni3Al(111) system. In the case of iron cluster
      growth on Al2O3/Ni3Al(111) the nucleation sites were independent of deposition
      temperature, yet the cluster shape showed a dependence. In this system, Fe
      clusters formed a regular hexagonal lattice on the Al2O3/Ni3Al(111).

PMID- 24445589
TI  - 5-epi-Torrubiellutin C shows antiproliferative activity on DU145 prostate cancer
      cells through inactivation of the AKT/mTOR pathway.
AB  - Cell-based assays for evaluation of the anticancer potential of a focused small
      molecule library have identified a few potential hit molecules. Among the hits
      identified, Torrubiellutins (3a) showed good anticancer potential across the
      cells used in screening assays. Torrubiellutins are isolated from fungal insects
      Torrubiella luteorostrata and diverse pharmacological effects for these have been
      reported. However, it is not known as to how Torrubiellutins act through
      signaling pathways inhibiting the growth of eukaryotic cells. The current study
      aimed to determine the anticancer potential of Torrubiellutins by defining the
      molecular mechanism of cytotoxicity using DU145 cells. The results showed that
      the inhibition of prostate cancer cell growth by 3a was associated with
      inhibition of anchorage-independent growth, cell migration, and, to a small
      extent, apoptosis-mediated cell death by caspase activation. The growth
      inhibitory effects of 3a are supported by inactivation of prosurvival pathways.
      Immunoblot analysis showed that the treatment of DU145 cells with 3a resulted in
      specific downregulation of AKT/mammalian target of rapamycin (mTOR) and its
      downstream effector proteins p70S6K, GSK3beta, and STAT3. On the basis of these
      findings, we propose that the changes observed in the AKT/mTOR signaling axis are
      new targets of 3a that are involved in its inhibitory activity on the
      proliferation of prostate cancer cells, suggesting its potential for further
      investigation as a promising anticancer agent. 

PMID- 24445590
TI  - Pigmentation in sand pear (Pyrus pyrifolia) fruit: biochemical characterization,
      gene discovery and expression analysis with exocarp pigmentation mutant.
AB  - Exocarp color of sand pear is an important trait for the fruit production and has
      caused our concern for a long time. Our previous study explored the different
      expression genes between the two genotypes contrasting for exocarp color, which
      indicated the different suberin, cutin, wax and lignin biosynthesis between the
      russet- and green-exocarp. In this study, we carried out microscopic observation
      and Fourier transform infrared spectroscopy analysis to detect the differences of
      tissue structure and biochemical composition between the russet- and green
      exocarp of sand pear. The green exocarp was covered with epidermis and cuticle
      which was replaced by a cork layer on the surface of russet exocarp, and the
      chemicals of the russet exocarp were characterized by lignin, cellulose and
      hemicellulose. We explored differential gene expression between the russet
      exocarp of 'Niitaka' and its green exocarp mutant cv. 'Suisho' using Illumina RNA
      sequencing. A total of 559 unigenes showed different expression between the two
      types of exocarp, and 123 of them were common to the previous study. The
      quantitative real time-PCR analysis supports the RNA-seq-derived gene with
      different expression between the two types of exocarp and revealed the
      preferential expression of these genes in exocarp than in mesocarp and fruit
      core. Gene ontology enrichment analysis revealed divorced expression of lipid
      metabolic process genes, transport genes, stress responsive genes and other
      biological process genes in the two types of exocarp. Expression changes in
      lignin metabolism-related genes were consistent with the different pigmentation
      of russet and green exocarp. Increased transcripts of putative genes involved the
      suberin, cutin and wax biosynthesis in 'Suisho' exocarp could facilitate
      deposition of the chemicals and take a role in the mutant trait responsible for
      the green exocarp. In addition, the divorced expression of ATP-binding cassette
      transporters involved in the trans-membrane transport of lignin, cutin, and
      suberin precursors suggests that the transport process could also affect the
      composition of exocarp and take a role in the regulation of exocarp pigmentation.
      Results from this study provide a base for the analysis of the molecular
      mechanism underlying sand pear russet/green exocarp mutation, and presents a
      comprehensive list of candidate genes that could be used to further investigate
      the trait mutation at the molecular level. 

PMID- 24445593
TI  - Fast nanomechanical spectroscopy of soft matter.
AB  - A method that combines high spatial resolution, quantitative and non-destructive
      mapping of surfaces and interfaces is a long standing goal in nanoscale
      microscopy. The method would facilitate the development of hybrid devices and
      materials made up of nanostructures of different properties. Here we develop a
      multifrequency force microscopy method that enables simultaneous mapping of
      nanomechanical spectra of soft matter surfaces with nanoscale spatial resolution.
      The properties include the Young's modulus and the viscous or damping
      coefficients. In addition, it provides the peak force and the indentation. The
      method does not limit the data acquisition speed nor the spatial resolution of
      the force microscope. It is non-invasive and minimizes the influence of the tip
      radius on the measurements. The same tip is used to measure in air heterogeneous
      interfaces with near four orders of magnitude variations in the elastic modulus,
      from 1 MPa to 3 GPa. 

PMID- 24445592
TI  - Preventive or curative postoperative noninvasive ventilation after thoracic
      surgery: still a grey zone?

PMID- 24445591
TI  - The modified rice alphaAmy8 promoter confers high-level foreign gene expression
      in a novel hypoxia-inducible expression system in transgenic rice seedlings.
AB  - Expression of alpha-amylase genes in rice is induced not only by sugar starvation
      and gibberellin (GA) but also by O2 deficiency. Promoters of two rice alpha
      amylase genes, alphaAmy3 and alphaAmy8, have been shown to direct high-level
      production of recombinant proteins in rice suspension cells and germinated seeds.
      In the present study, we modified the cis-acting DNA elements within the sugar/GA
      response complex (SRC/GARC) of alphaAmy8 promoter. We found that addition of a G
      box and duplicated TA box leads to high-level expression of alphaAmy8 SRC/GARC
      and significantly enhances alphaAmy8 promoter activity in transformed rice cells
      and germinated transgenic rice seeds. We also show that these modifications have
      drastically increased the activity of alphaAmy8 promoter in rice seedlings under
      hypoxia. Our results reveal that the G box and duplicated TA box may play
      important roles in stimulating promoter activity in response to hypoxia in rice.
      The modified alphaAmy8 promoter was used to produce the recombinant human
      epidermal growth factor (hEGF) in rice cells and hypoxic seedlings. We found that
      the bioactive recombinant hEGF are stably produced and yields are up to 1.8% of
      total soluble protein (TSP) in transformed rice cells. The expression level of
      synthetic hEGF containing preferred rice codon usage comprises up to 7.8% of TSP
      in hypoxic transgenic seedlings. Our studies reveal that the modified alphaAmy8
      promoter can be applicable in establishing a novel expression system for the high
      level production of foreign proteins in transgenic rice cells and seedlings under
      hypoxia.

PMID- 24445594
TI  - Bilateral radial nerve compression neuropathy in the newborn.
AB  - PURPOSE: This study aims to discuss the diagnosis and management of radial nerve
      compression neuropathy in the newborn. METHODS: A personal case is presented,
      followed by a review and analysis of clinically similar cases identified via a
      PubMed search of published medical literature. RESULTS: We report a case of a
      term newborn with bilateral radial neuropathy at the humerus level. Despite
      severe axonal involvement in the electrophysiological evaluation, the patient
      showed complete bilateral recovery after 3 months of follow-up. CONCLUSIONS:
      Isolated radial nerve palsy is a rare event in the newborn. The condition does
      not require surgical treatment and usually proceeds to full and rapid spontaneous
      recovery.

PMID- 24445595
TI  - A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy:
      the "SMART" approach for resectable malignant pleural mesothelioma.
AB  - INTRODUCTION: We developed an innovative approach for malignant pleural
      mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic
      intensity-modulated radiation therapy (IMRT) followed by extrapleural
      pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery
      for Mesothelioma After Radiation Therapy (SMART). METHODS: All resectable
      clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible.
      Patients received 25 Gy in five daily fractions during 1 week to the entire
      ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by
      EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was
      offered to ypN2 patients on final pathologic findings. The primary end point was
      treatment-related mortality and secondary end points were overall survival,
      disease-free survival, treatment-related morbidity, and patterns of failure.
      RESULTS: Targeted accrual of 25 patients was completed between November 2008 and
      October 2012. All patients completed SMART. IMRT was well tolerated with no grade
      3+ toxicities. EPP was performed 6 +/- 2 days after completing IMRT without any
      perioperative mortality. Thirteen patients developed grade 3+ surgical
      complications. One patient (4%) died from treatment-related toxicity (empyema)
      during follow-up. All but one patient had stage III or IV disease on final
      pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy.
      After a median follow-up of 23 months (range, 6-51), the cumulative 3-year
      survival reached 84% in epithelial subtypes compared with 13% in biphasic
      subtypes (p = 0.0002). CONCLUSIONS: SMART is feasible in resectable MPM patients.
      This innovative protocol presents encouraging results and supports future studies
      looking at long-term outcome in patients with epithelial subtypes.

PMID- 24445596
TI  - Childhood and parental diagnostic radiological procedures and risk of childhood
      brain tumors.
AB  - PURPOSE: Childhood brain tumors (CBT) are the second most common type of
      childhood cancer and the leading cause of childhood cancer mortality. Few causes
      of CBT are known, but parental, fetal, and early life exposures are likely to be
      important given the early age at diagnosis of many cases. We aimed to investigate
      whether parents' diagnostic radiological procedures before conception, in the
      mother during pregnancy or the child's procedures were associated with an
      increased risk of CBT. METHODS: This population-based case-control study was
      conducted between 2005 and 2010. Cases were identified through all ten Australian
      pediatric oncology centers, and controls via nationwide random-digit dialing;
      frequency-matched to cases on age, sex and state of residence. Information on
      radiological exposures in the time periods of interest was obtained for 306 case
      and 950 control families through mailed questionnaires. Analysis used
      unconditional logistic regression, adjusting for matching variables and potential
      confounders. RESULTS: We found no evidence of positive associations between risk
      of CBT overall and childhood or parental pre-pregnancy radiological procedures.
      Increased ORs for high-grade gliomas associated with childhood radiological
      procedures were based on small numbers and may be due to chance. CONCLUSIONS:
      Given the evidence for an increased risk of CBT in cohort studies of computed
      tomography (CT) in childhood, the lack of such an association in our study may be
      due to the reduced intensity of CTs after 2001. Future research to investigate
      the safety of fetal exposure to more intense procedures like CT scans is needed.

PMID- 24445597
TI  - Disparities in survival improvement for metastatic colorectal cancer by
      race/ethnicity and age in the United States.
AB  - PURPOSE: Previous studies documented significant increase in overall survival for
      metastatic colorectal cancer (CRC) since the late 1990s coinciding with the
      introduction and dissemination of new treatments. We examined whether this
      survival increase differed across major racial/ethnic populations and age groups.
      METHODS: We identified patients diagnosed with primary metastatic colorectal
      cancer during 1992-2009 from 13 population-based cancer registries of the
      National Cancer Institute's Surveillance, Epidemiology, and End Results Program,
      which cover about 14 % of the US population. The 5-year cause-specific survival
      rates were calculated using SEER*Stat software. RESULTS: From 1992-1997 to 2004
      2009, 5-year cause-specific survival rates increased significantly from 9.8 % (95
      % CI 9.2-10.4) to 15.7 % (95 % CI 14.7-16.6) in non-Hispanic whites and from 11.4
      % (95 % CI 9.4-13.6) to 17.7 % (95 % CI 15.1-20.5) in non-Hispanic Asians, but
      not in non-Hispanic blacks [from 8.6 % (95 % CI 7.2-10.1) to 9.8 % (95 % CI 8.1
      11.8)] or Hispanics [from 14.0 % (95 % CI 11.8-16.3) to 16.4 % (95 % CI 14.0
      19.0)]. By age group, survival rates increased significantly for the 20-64-year
      age group and 65 years or older age group in non-Hispanic whites, although the
      improvement in the older non-Hispanic whites was substantially smaller. Rates
      also increased in non-Hispanic Asians for the 20-64-year age group although
      marginally nonsignificant. In contrast, survival rates did not show significant
      increases in both younger and older age groups in non-Hispanic blacks and
      Hispanics. CONCLUSION: Non-Hispanic blacks, Hispanics, and older patients
      diagnosed with metastatic CRC have not equally benefitted from the introduction
      and dissemination of new treatments.

PMID- 24445598
TI  - Residential treatment for individuals with substance use disorders: assessing the
      evidence.
AB  - OBJECTIVE: Residential treatment is a commonly used direct intervention for
      individuals with substance use or co-occurring mental and substance use disorders
      who need structured care. Treatment occurs in nonhospital, licensed residential
      facilities. Models vary, but all provide safe housing and medical care in a 24
      hour recovery environment. This article describes residential treatment and
      assesses the evidence base for this service. METHODS: Authors evaluated research
      reviews and individual studies from 1995 through 2012. They searched major
      databases: PubMed, PsycINFO, Applied Social Sciences Index and Abstracts,
      Sociological Abstracts, and Social Services Abstracts. They chose from three
      levels of evidence (high, moderate, and low) and described the evidence of
      service effectiveness. RESULTS: On the basis of eight reviews and 21 individual
      studies not included in prior reviews, the level of evidence for residential
      treatment for substance use disorders was rated as moderate. A number of
      randomized controlled trials were identified, but various methodological
      weaknesses in study designs-primarily the appropriateness of the samples and
      equivalence of comparison groups-decreased the level of evidence. Results for the
      effectiveness of residential treatment compared with other types of treatment for
      substance use disorders were mixed. Findings suggested either an improvement or
      no difference in treatment outcomes. CONCLUSIONS: Residential treatment for
      substance use disorders shows value and merits ongoing consideration by policy
      makers for inclusion as a covered benefit in public and commercially funded
      plans. However, research with greater specificity and consistency is needed.

PMID- 24445599
TI  - Gene silencing associated with SWI/SNF complex loss during NSCLC development.
AB  - The SWI/SNF chromatin-remodeling complex regulates gene expression and alters
      chromatin structures in an ATP-dependent manner. Recent sequencing efforts have
      shown mutations in BRG1 (SMARCA4), one of two mutually exclusive ATPase subunits
      in the complex, in a significant number of human lung tumor cell lines and
      primary non-small cell lung carcinoma (NSCLC) clinical specimens. To determine
      how BRG1 loss fuels tumor progression in NSCLC, molecular profiling was performed
      after restoration of BRG1 expression or treatment with a histone deacetylase
      inhibitor or a DNA methyltransferase (DNMT) inhibitor in a BRG1-deficient NSCLC
      cells. Importantly, validation studies from multiple cell lines revealed that
      BRG1 reexpression led to substantial changes in the expression of CDH1, CDH3,
      EHF, and RRAD that commonly undergo silencing by other epigenetic mechanisms
      during NSCLC development. Furthermore, treatment with DNMT inhibitors did not
      restore expression of these transcripts, indicating that this common mechanism of
      gene silencing did not account for their loss of expression. Collectively, BRG1
      loss is an important mechanism for the epigenetic silencing of target genes
      during NSCLC development. IMPLICATIONS: Inactivation of the SWI/SNF complex
      provides a novel mechanism to induce gene silencing during NSCLC development.

PMID- 24445601
TI  - Advances in NKG2D ligand recognition and responses by NK cells.
AB  - The natural killer (NK) group 2 member D (NKG2D) is an activating immune receptor
      expressed on NK cells, cytotoxic T cells and a subset of other T cells. It has an
      important role in the recognition and lysis of a variety of infected and tumor
      cells. Despite significant gains in our understanding of NKG2D, the relevance of
      NKG2D and its ligands in human diseases has only recently started to emerge.
      Here, we present an overview of the recent advances in NKG2D biology, discuss the
      expression of NKG2D ligands in cancer patients and evaluate the diagnostic and
      prognostic potential of NKG2D ligands.

PMID- 24445600
TI  - Divergent outcomes following transcytosis of IgG targeting intracellular and
      extracellular chlamydial antigens.
AB  - Antibodies can have a protective but non-essential role in natural chlamydial
      infections dependent on antigen specificity and antibody isotype. IgG is the
      dominant antibody in both male and female reproductive tract mucosal secretions,
      and is bi-directionally trafficked across epithelia by the neonatal Fc receptor
      (FcRn). Using pH-polarized epididymal epithelia grown on Transwells, IgG
      specifically targeted at an extracellular chlamydial antigen; the major outer
      membrane protein (MOMP), enhanced uptake and translocation of infection at pH 6
      6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely,
      FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion
      membrane protein A (IncA), induced aberrant inclusion morphology, recruited
      autophagic proteins independent of lysosomes and significantly reduced infection.
      Challenge of female mice with MOMP-specific IgG-opsonized Chlamydia muridarum
      delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP
      IgG elicited by immunization afforded no protection against testicular chlamydial
      infection, whereas the transcytosis of IncA-IgG significantly reduced testicular
      chlamydial burden. Together these data show that the protective and pathological
      effects of IgG are dependent on FcRn-mediated transport as well as the
      specificity of IgG for intracellular or extracellular antigens. 

PMID- 24445603
TI  - Differential effects of propranolol on conditioned hyperactivity and locomotor
      sensitization induced by morphine in rats.
AB  - According to memory reconsolidation theory, when long-term memory is reactivated
      by relevant clues, the memory traces become labile, which can be altered by
      pharmacological manipulations. Accumulating evidence reveals that memory related
      to drug abuse can be erased by disrupting reconsolidation process. We used an
      animal model that could simultaneously measure conditioned hyperactivity and
      locomotor sensitization induced by morphine. beta-Adrenoceptor antagonist
      propranolol or saline were administered following conditioned stimuli (CS) or a
      small dose of morphine reactivation. The results showed that the conditioned
      hyperactivity could be disrupted by propranolol treatment following CS
      reactivation. However, the expression of locomotor sensitization could not be
      disrupted by propranolol administration following CS or morphine reactivation.
      Furthermore, morphine injection and propranolol intervention enhanced the
      locomotor sensitization effect. These data suggest that blocking the
      reconsolidation process can disrupt the conditioned hyperactivity induced by
      environmental cues associated with morphine treatment, but not morphine-induced
      locomotor sensitization.

PMID- 24445604
TI  - Defective autophagosome trafficking contributes to impaired autophagic flux in
      coronary arterial myocytes lacking CD38 gene.
AB  - AIM: Autophagic flux is an important process during autophagy maturation in
      smooth muscle cells. However, the molecular mechanisms underlying autophagic flux
      in these cells are largely unknown. Here, we revealed a previously undefined role
      of CD38, an enzyme that metabolizes NADP(+) into NAADP, in the regulation of
      autophagic flux in coronary arterial myocytes (CAMs). METHODS AND RESULTS: In
      vivo CD38 gene knockout mice (CD38(-/-)) fed the high-fat Western diet showed
      increased accumulation of autophagosomes in coronary arterial media compared with
      that in wild-type (CD38(+/+)) mice, suggesting that CD38 gene deletion results in
      a defective autophagic process in CAMs of coronary arteries. In primary cultured
      CAMs, CD38 gene deletion markedly enhanced 7-ketocholesterol (7-Ket, an
      atherogenic stimulus and autophagy inducer)-induced accumulation of
      autophagosomes and increased expression of an autophagic marker, LC3B. However,
      no difference in autophagosome formation was observed between CD38(+/+) and CD38(
      /-) CAMs when autophagic flux was blocked, which indicates that CD38 regulates
      autophagic flux rather than induction of autophagosome formation. Further, 7-Ket
      induced formation of autophagolysosomes was markedly attenuated in CD38(-/-) CAMs
      compared with CD38(+/+) CAMs. Mechanistically, CD38 gene deletion markedly
      inhibited 7-Ket-induced dynein activation and autophagosome trafficking, which
      were associated with attenuated lysosomal Ca(2+) release. Importantly, coronary
      arterial smooth muscle from CD38(-/-) mice fed the Western diet exhibited
      phenotypic changes towards a more dedifferentiated state with abnormal
      extracellular matrix metabolism. CONCLUSION: Taken together, these results
      suggest that CD38 plays a critical role in autophagosome trafficking and fusion
      with lysosomes, thus controlling autophagic flux in CAMs under atherogenic
      stimulation.

PMID- 24445602
TI  - Cell biological steps and checkpoints in accessing NK cell cytotoxicity.
AB  - Natural killer (NK) cell-mediated cytotoxicity is governed by the formation of a
      lytic immune synapse in discrete regulated steps, which give rise to an extensive
      array of cellular checkpoints in accessing NK cell-mediated cytolytic defense.
      Appropriate progression through these cell biological steps is critical for the
      directed secretion of specialized secretory lysosomes and subsequent target cell
      death. Here we highlight recent discoveries in the formation of the NK cell
      cytolytic synapse as well as the molecular steps and cell biological checkpoints
      required for this essential host defense process.

PMID- 24445605
TI  - beta(IV)-Spectrin regulates TREK-1 membrane targeting in the heart.
AB  - AIMS: Cardiac function depends on the highly regulated and co-ordinate activity
      of a large ensemble of potassium channels that control myocyte repolarization.
      While voltage-gated K(+) channels have been well characterized in the heart, much
      less is known about regulation and/or targeting of two-pore K(+) channel (K(2P))
      family members, despite their potential importance in modulation of heart
      function. METHODS AND RESULTS: Here, we report a novel molecular pathway for
      membrane targeting of TREK-1, a mechano-sensitive K(2P) channel regulated by
      environmental and physical factors including membrane stretch, pH, and
      polyunsaturated fatty acids (e.g. arachidonic acid). We demonstrate that beta(IV)
      spectrin, an actin-associated protein, is co-localized with TREK-1 at the myocyte
      intercalated disc, associates with TREK-1 in the heart, and is required for TREK
      1 membrane targeting. Mice expressing beta(IV)-spectrin lacking TREK-1 binding
      (qv(4J)) display aberrant TREK-1 membrane localization, decreased TREK-1
      activity, delayed action potential repolarization, and arrhythmia without
      apparent defects in localization/function of other cardiac potassium channel
      subunits. Finally, we report abnormal beta(IV)-spectrin levels in human heart
      failure. CONCLUSIONS: These data provide new insight into membrane targeting of
      TREK-1 in the heart and establish a broader role for beta(IV)-spectrin in
      organizing functional membrane domains critical for normal heart function.

PMID- 24445606
TI  - Can unilateral-approach minimally invasive transforaminal lumbar interbody fusion
      attain indirect contralateral decompression? A preliminary report of 66 MRI
      analysis.
AB  - PURPOSE: Few studies have measured the amount of indirect decompression at the
      contralateral neural foramen after unilateral-approach minimally invasive
      transforaminal lumbar interbody fusion (MITLIF). This study examined the amount
      of intraoperative indirect decompression at the contralateral neural foramen
      after a unilateral-approach MITLIF in patients with bilateral foraminal stenosis.
      METHODS: From February 2009 to October 2012, 66 consecutive patients with
      bilateral foraminal stenosis underwent unilateral-approach MITLIF and
      postoperative magnetic resonance imaging (MRI). Direct decompression was
      performed at the central canal and approach-side neural foramen, while indirect
      decompression using cage distraction was pursued at the contralateral neural
      foramen. Qualitative parameters of the central canal (dural sac morphology) and
      neural foramen (foramen morphology) were analyzed using pre- and post-operative
      MRI. Quantitative measurement on the central canal (dural sac cross-sectional
      area) and neural foramen (foramen height and width) were also measured. RESULTS:
      A total of 69 intervertebral levels in the 66 patients were analyzed. Qualitative
      parameters of the central canal and contralateral neural foramen improved
      significantly after unilateral-approach MITLIF (both P < 0.001). The mean dural
      sac cross-sectional area increased from 51.1 +/- 28.8 to 84.8 +/- 30.2 mm(2) (P <
      0.001). The mean preoperative contralateral foramen height, maximum foramen
      width, and minimum foramen width were 11.8 +/- 2.0, 4.9 +/- 1.5, and 1.5 +/- 0.7
      mm, respectively, and these values increased postoperatively to 14.7 +/- 2.5, 6.5
      +/- 1.8, and 2.4 +/- 1.0 mm, respectively (all P < 0.001). CONCLUSION:
      Quantitative and qualitative parameters of the central canal and contralateral
      neural foramen increased significantly after unilateral-approach MITLIF.

PMID- 24445607
TI  - Cationic lipophosphoramidates with two different lipid chains: synthesis and
      evaluation as gene carriers.
AB  - Cationic lipids constitute a family of synthetic vectors commonly used for
      nucleic acids delivery. We herein report the results of a systematic study that
      aimed to compare the transfection efficacies of cationic lipophosphoramidates
      possessing either two identical lipid chains (termed symmetric cationic lipids)
      or two different lipid chains (non-symmetric cationic lipids). In addition, we
      also compared the transfection results of such a 'molecular approach' (the two
      different lipid chains being included in the same molecule) with those of a
      'supramolecular approach' in which two types of symmetrical cationic lipids were
      mixed in one liposomal formulation. Thus, the present work allowed us first to
      optimize the methods used to synthesize non-symmetric cationic
      lipophosphoramidates. In addition, we could also identify two non-symmetric
      cationic lipids exhibiting high transfection efficiencies with a series of
      mammalian cell lines, both vectors being characterized by a single phytanyl chain
      and either an oleyl or a lauryl lipid chain. 

PMID- 24445608
TI  - Traumatic brain injury carries long term health risks, finds study.

PMID- 24445609
TI  - Reply to the 'Comment on "Volume shrinkage of a metal-organic framework host
      induced by the dispersive attraction of guest gas molecules"' by F.-X. Coudert,
      A. H. Fuchs, and A. V. Neimark, Phys. Chem. Chem. Phys.

PMID- 24445610
TI  - Atomistic amorphous/crystalline interface  modelling for superlattices and
      core/shell  nanowires.
AB  - In this paper we present a systematic and well controlled procedure for building
      atomistic amorphous/crystalline interfaces in silicon, dedicated to the molecular
      dynamics simulations of superlattices and core/shell nanowires. The obtained
      structures depend on the technique used to generate the amorphous phase and their
      overall quality is estimated through comparisons with structural information and
      interfacial energies available from experimental and theoretical results. While
      most of the related studies focus on a single planar interface, we consider here
      both the generation of multiple superlattice planar interfaces and core/shell
      nanowire structures. The proposed method provides periodic homogeneous and
      reproducible, atomically sharp and defect free interface configurations at low
      temperature and pressure. We also illustrate how the method may be used to
      predict the thermal transport properties of composite crystalline/amorphous
      superlattices.

PMID- 24445613
TI  - Mechanisms and efficacy of dietary FODMAP restriction in IBS.
AB  - IBS is a debilitating condition that markedly affects quality of life. The
      chronic nature, high prevalence and associated comorbidities contribute to the
      considerable economic burden of IBS. The pathophysiology of IBS is not completely
      understood and evidence to guide management is variable. Interest in dietary
      intervention continues to grow rapidly. Ileostomy and MRI studies have
      demonstrated that some fermentable carbohydrates increase ileal luminal water
      content and breath hydrogen testing studies have demonstrated that some
      carbohydrates also increase colonic hydrogen production. The effects of
      fermentable carbohydrates on gastrointestinal symptoms have also been well
      described in blinded, controlled trials. Dietary restriction of fermentable
      carbohydrates (popularly termed the 'low FODMAP diet') has received considerable
      attention. An emerging body of research now demonstrates the efficacy of
      fermentable carbohydrate restriction in IBS; however, limitations still exist
      with this approach owing to a limited number of randomized trials, in part due to
      the fundamental difficulty of placebo control in dietary trials. Evidence also
      indicates that the diet can influence the gut microbiota and nutrient intake.
      Fermentable carbohydrate restriction in people with IBS is promising, but the
      effects on gastrointestinal health require further investigation. 

PMID- 24445614
TI  - Pancreatic cancer: pancreatic tumour formation and recurrence after radiotherapy
      are blocked by targeting CD44.

PMID- 24445617
TI  - Achilles tendon allograft for augmentation of the Hanssen patellar bone grafting.
AB  - PURPOSE: Severe patellar bone loss precludes the insertion of another patellar
      implant in revision total knee arthroplasty (TKA) and weakens the attachment of
      the patella to the quadriceps tendon. Hanssen described securing a tissue flap to
      the patellar rim allows the delivery of cancellous bone graft into the patellar
      bone defect. The purpose of this study is to describe the surgical technique and
      early clinical results of a modified Hanssen patelloplasty with an Achilles
      tendon allograft. METHODS: The modified technique described in three patients
      undergoing revision TKA aims to augment the extensor mechanism by securing an
      Achilles tendon allograft to the proximal part of the patellar tendon and the
      distal quadriceps tendon using mattress sutures. This serves to reinforce the
      extensor mechanism and decrease the risk of a tear of its patellar attachment.
      The patellar bone defect is grafted using corticocancellous bone chips. RESULTS:
      Over a 12- to 48-month follow-up, all reconstructions healed with an increase in
      patellar bone thickness. No patient had any extensor lag, and all patients
      achieved 110 degrees -125 degrees  of flexion. The Western Ontario and McMaster
      University knee scores improved from 53 (23-88) preoperatively to 88.5 (66-100)
      at last follow-up, with no reported complications. CONCLUSIONS: Augmentation of
      the extensor mechanism with an Achilles tendon allows for early mobilization and
      excellent postoperative range of motion in patients with large patella bone
      defects and imminent patella fracture. LEVEL OF EVIDENCE: IV.

PMID- 24445619
TI  - Antitumor efficacy of argon-helium cryoablation-generated dendritic cell vaccine
      in glioma.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that play a critical
      role in priming tumor immune responses. We investigated the mechanisms of
      antitumor efficacy of DCs pulsed with argon-helium-cryotreated glioma cells.
      There was significant upregulation of maturation markers (CD80, CD86, MHC-I, and
      MHC-II) in argon-helium freeze-thawed lysate-pulsed DCs. The concentration of
      interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha, and IL-12 secreted
      by lysate-pulsed DCs was increased. The concentration of interferon-gamma
      secreted by T cells stimulated by lysate-pulsed DCs was increased. The
      cytotoxicity assay showed that T cells stimulated by lysate-pulsed DCs could kill
      glioma cells significantly more effectively. Our results suggest that argon
      helium freeze-thawed lysate-pulsed DCs in vitro can promote DC maturation and
      enhance DC antigen-presenting function, and induce cytotoxic T lymphocytes to
      kill tumor cells. Therefore, the combination of argon-helium cryoablation and DC
      vaccine may represent a novel treatment method for glioma. 

PMID- 24445618
TI  - Photosynthetic responses of sun- and shade-grown barley leaves to high light: is
      the lower PSII connectivity in shade leaves associated with protection against
      excess of light?
AB  - In this study, we have compared photosynthetic performance of barley leaves
      (Hordeum vulgare L.) grown under sun and shade light regimes during their entire
      growth period, under field conditions. Analyses were based on measurements of
      both slow and fast chlorophyll (Chl) a fluorescence kinetics, gas exchange,
      pigment composition; and of light incident on leaves during their growth. Both
      the shade and the sun barley leaves had similar Chl a/b and Chl/carotenoid
      ratios. The fluorescence induction analyses uncovered major functional
      differences between the sun and the shade leaves: lower connectivity among
      Photosystem II (PSII), decreased number of electron carriers, and limitations in
      electron transport between PSII and PSI in the shade leaves; but only low
      differences in the size of PSII antenna. We discuss the possible protective role
      of low connectivity between PSII units in shade leaves in keeping the excitation
      pressure at a lower, physiologically more acceptable level under high light
      conditions. 

PMID- 24445620
TI  - Substance abuse intensive outpatient programs: assessing the evidence.
AB  - OBJECTIVE: Substance abuse intensive outpatient programs (IOPs) are direct
      services for people with substance use disorders or co-occurring mental and
      substance use disorders who do not require medical detoxification or 24-hour
      supervision. IOPs are alternatives to inpatient and residential treatment. They
      are designed to establish psychosocial supports and facilitate relapse management
      and coping strategies. This review assessed the evidence base for IOPs. METHODS:
      Authors searched major databases: PubMed, PsycINFO, Applied Social Sciences Index
      and Abstracts, Sociological Abstracts, Social Services Abstracts, Published
      International Literature on Traumatic Stress, ERIC, and CINAHL. They identified
      12 individual studies and one review published between 1995 and 2012. They chose
      from three levels of research evidence (high, moderate, and low) based on
      benchmarks for the number of studies and quality of their methodology. They also
      described evidence of service effectiveness. RESULTS: Based on the quality of
      trials, diversity of settings, and consistency of outcomes, the level of evidence
      for IOPs was rated high. Multiple randomized trials and naturalistic analyses
      that compared IOPs with inpatient or residential care found comparable outcomes.
      All studies reported reductions in alcohol and drug use. However, substantial
      variability in the operationalization of IOPs and outcome measures was apparent.
      CONCLUSIONS: IOPs are an important part of the continuum of care for substance
      use disorders. They are as effective as inpatient treatment for most individuals.
      Public and commercial health plans should consider IOP services as a covered
      health benefit. Standardization of the elements included in IOPs may improve
      their quality and effectiveness.

PMID- 24445621
TI  - Initiation of ECMO for ventilator-dependent respiratory failure in an infant with
      Pompe's.
AB  - We present a 7-month-old male with Pompe's disease with respiratory failure
      requiring extracorporeal membrane oxygenation that received enzyme replacement
      therapy. There are no published cases of the use of extracorporeal membrane
      oxygenation in a patient with Pompe's disease, or the use of enzyme replacement
      therapy in the setting of acute respiratory failure. 

PMID- 24445622
TI  - Hot on the trail of "I know it when I see it!".

PMID- 24445623
TI  - Airway evaluation: thin sliced and packaged.

PMID- 24445624
TI  - Hope for the best, but prepare for the worst.

PMID- 24445625
TI  - Postoperative complications associated with obstructive sleep apnea: time to wake
      up!

PMID- 24445626
TI  - Platelet dysfunction as measured by a point-of-care monitor is an independent
      predictor of high blood loss in cardiac surgery.
AB  - BACKGROUND: Excessive bleeding carries a heavy burden of illness in cardiac
      surgery. Although platelet dysfunction is considered to be an important cause, it
      is not routinely measured. Our objective was to explore the relationship between
      platelet dysfunction and blood loss in cardiac surgery. METHODS: In 100
      consenting patients undergoing cardiac surgery requiring cardiopulmonary bypass,
      platelet function was measured before, during, and after bypass with a point-of
      care device that compares platelet counts before and after exposure to an
      agonist. Clinicians were blinded to the results of testing. Patients whose
      calculated blood loss was part of the highest quartile for the cohort were
      classified as having had high blood loss. The independent relationship between
      platelet function and high blood loss was measured with the aid of multivariable
      Poisson regression modeling (with a robust error variance) that controlled for
      patients' overall risk of high blood loss. RESULTS: Calculated blood loss was
      negatively skewed with a median of 798 mL (25th and 75th percentiles of 380 and
      1775 mL). Patients whose blood loss exceeded 1770 mL were classified as having
      had high blood loss, and 25 patients met this criterion. There was 1 death in the
      high blood loss group unrelated to hemorrhage. After adjusting for bleeding risk,
      each 10 * 10/L increase in collagen-activated functional platelet count during
      rewarming and postprotamine, respectively, was associated with a relative risk of
      0.89 (95% confidence interval, 0.82-0.97; P = 0.006) and 0.87 (95% confidence
      interval, 0.78-0.98; P = 0.02) for high blood loss. CONCLUSIONS: Platelet
      dysfunction, as measured by a point-of-care method during rewarming and
      postprotamine, is independently associated with high blood loss in cardiac
      surgery. Additional studies are needed to determine whether the incorporation of
      this assay into blood management algorithms might help rationalize blood
      transfusion therapy, potentially reducing blood loss and improving clinical
      outcomes.

PMID- 24445627
TI  - Stationary versus agitated storage of whole blood during acute normovolemic
      hemodilution.
AB  - BACKGROUND: Acute normovolemic hemodilution is an intraoperative technique to
      reduce the number of red blood cells lost in shed blood during surgery. Standard
      guidelines for storage of platelets recommend constant gentle agitation to
      maintain gas exchange for the metabolically active platelets. The collected whole
      blood (WB) for acute normovolemic hemodilution remains stationary for as long as
      8 hours before reinfusion. We hypothesized that gentle agitation of WB throughout
      storage would improve the coagulation properties of the WB at the time of
      reinfusion. METHODS: WB was collected from 10 volunteer donors and control
      samples taken. The units were split in 2 storage groups: agitated (rocked) and
      stationary (unrocked). Cell counts and fibrinogen levels, as well as
      thromboelastography (TEG(r)) measurements, including TEG(r) PlateletMapping(r)
      assays, were performed on the control sample and the test samples after 8 hours
      of rocked or unrocked storage at room temperature. RESULTS: Nine units WB from 9
      different healthy volunteers were tested. There were no significant differences
      in hematocrit, hemoglobin, red blood cells counts, platelet counts, or fibrinogen
      levels between the control samples and the rocked and unrocked WB samples. WB
      coagulation as measured by TEG(r) was preserved during the 8-hour storage period
      in both the rocked and unrocked samples. There were no significant differences
      between the control, rocked, and unrocked samples in time to initiate clotting,
      time of clot formation, rate of clot formation, or maximum strength of clot
      values. There were also no significant differences in the fibrin contribution to
      clot strength between the control, rocked, and unrocked samples, and no
      significant difference between the platelet activation from adenosine diphosphate
      or arachidonic acid among any of the 3 groups. CONCLUSIONS: Given the small
      sample size, there is no statistical evidence on which to reject the null
      hypothesis of there being no difference in the changes from the baseline between
      coagulation function as measured by TEG(r) between WB that is either agitated or
      kept stationary for 8 hours. These findings need to be confirmed in a larger
      study.

PMID- 24445628
TI  - The effectiveness of different functional fibrinogen polymerization assays in
      eliminating platelet contribution to clot strength in thromboelastometry.
AB  - BACKGROUND: Viscoelastic tests such as functional fibrinogen polymerization
      assays (FFPAs) in thrombelastography (TEG(r)) or thromboelastometry (ROTEM(r))
      measure clot elasticity under platelet inhibition. Incomplete platelet inhibition
      influences maximum clot firmness (MCF) of FFPAs. We compared the ability of
      existing and newly developed FFPAs to eliminate the platelet contribution to clot
      strength. METHODS: MCF of whole blood (WB), platelet-rich plasma (PRP), and
      platelet-poor plasma samples was recorded using a ROTEM device with different
      FFPAs, including the TEG functional fibrinogen test (FFTEG) and different ROTEM
      based assays: the standard fib-tem reagent (FIBTEM), a lyophilized single-portion
      reagent fib-tem S (FIBTEM-S), a newly developed reagent FIBTEM PLUS, as well as
      FIBTEM or the standard extrinsic activation reagent ex-tem(r) (EXTEM) combined
      with 10-MUg abciximab (FIBTEM-ABC/EXTEM-ABC). RESULTS: In WB (platelet count
      [mean +/- SD], 183 +/- 37 * 10/MUL; plasma fibrinogen concentration, 2.49 +/-
      0.58 g/L), FFTEG and EXTEM-ABC showed higher MCF (15.7 +/- 2.8 mm) than FIBTEM or
      FIBTEM-S (11.4 +/- 3.3 mm, P < 0.001), whereas FIBTEM-ABC and FIBTEM PLUS
      resulted in lower MCF (9.3 +/- 2.8 mm, P < 0.001). In 2 different PRP samples,
      with platelet counts of 407 +/- 80 * 10/MUL and 609 +/- 127 * 10/MUL, FIBTEM-ABC
      and FIBTEM PLUS reduced platelet contribution to clot strength within 95%
      confidence interval limits of -1.4 to 0.1 mm and -1.2 to 0.4 mm, respectively.
      Using all FFPAs it was observed that the Pearson correlation coefficient between
      plasma fibrinogen concentration and WB MCF was high (range, 0.75-0.93) and
      significant, regardless of the underlying platelet inhibiting component.
      Evaluating differences in the interception of regression lines by using analysis
      of covariance, we compared platelet-poor plasma and both PRP samples within the
      same assays and found that in contrast to the FIBTEM-ABC and FIBTEM PLUS assays,
      the FFTEG, EXTEM-ABC, FIBTEM, and FIBTEM-S methods still detected residual
      platelet activity and grossly overestimated fibrin clot strength in samples with
      high platelet counts. CONCLUSIONS: FFPAs based solely on glycoprotein-IIb/IIIa
      inhibition, such as FFTEG or EXTEM-ABC, are less effective than cytochalasin D
      based assays, such as FIBTEM or FIBTEM-S, at inhibiting the platelet component of
      clot strength. The FIBTEM PLUS assay, and the combination of FIBTEM and
      abciximab, sufficiently inhibits platelet contribution to clot elasticity. The
      combination of a glycoprotein-IIb/IIIa receptor blocker and cytochalasin D allows
      evaluation of functional fibrinogen polymerization without platelet "noise." In a
      clinical setting, the significance of potent platelet inhibition ensures a more
      accurate assessment of MCF and therefore the need for fibrinogen supplementation
      therapy. Further studies are necessary to investigate the application and impact
      of these tests in a clinical situation.

PMID- 24445629
TI  - Increased glycemic variability in patients with elevated preoperative HbA1C
      predicts adverse outcomes following coronary artery bypass grafting surgery.
AB  - BACKGROUND: In the setting of protocolized glycemic control, the relationship
      between postoperative glycemic variability on major adverse events (MAEs) after
      cardiac surgery is unknown for patients with increased preoperative hemoglobin
      A1C (HbA1C >6.5%). In this study, we sought to establish (a) whether
      postoperative glycemic variability is associated with MAEs after CABG surgery and
      (b) whether preoperative HbA1C could identify patients at increased risk of
      postoperative glycemic variability. METHODS: Patients undergoing coronary artery
      bypass grafting with or without valvular surgery from January 2008 to May 2011
      were enrolled in this prospective, single-center, observational cohort study.
      Demographic, intraoperative, and postoperative outcome data were obtained from
      institutional data collected for the Society of Thoracic Surgery (STS) database.
      The primary outcome, MAE was a composite of in-hospital death, myocardial
      infarction (MI), reoperations, sternal infection, cardiac tamponade, pneumonia,
      stroke, or renal failure. Glycemic variability in the postoperative period was
      assessed by the coefficient of variation (CV). CV was used as quartiles for the
      multivariate logistic regression. Variable selection in multivariable modeling
      was based on clinical and statistical significance and was performed in a
      hierarchical fashion. RESULTS: Of the 1461 patients enrolled, 9.8% had an MAE.
      Based on the established target of HbA1C <6.5% for the diagnosis of diabetes
      mellitus, we considered HbA1C as a binary variable (<6.5% and >=6.5%) in our
      primary analysis. Multivariate logistic regression analyses for the preoperative
      variables only revealed that preoperative HbA1C (odds ratio [OR], 1.6; 95%
      confidence interval [CI], 1.1-2.3; P = 0.02), history of MI (OR, 1.9; 95% CI, 1.3
      2.8; P = 0.001), and STS risk score per quartile (OR, 1.7; 95% CI, 1.4-2.1; P <
      0.001) were associated with MAEs. When postoperative variables were included in
      the analyses, postoperative glycemic variability (CV per quartile) in the
      intensive care unit (OR, 1.3; 95% CI, 1.1-1.5; P = 0.03), mean glucose levels
      averaged over the first 4 postoperative hours (OR, 1.2; 95% CI, 1.0-1.4; P =
      0.03), history of MI (OR, 1.8; 95% CI, 1.2-2.6; P = 0.004), and STS risk score
      per quartile (OR, 1.6; 95% CI, 1.3-2.0; P < 0.001) were associated with MAEs.
      Glycemic variability as assessed by CV was increased postoperatively in patients
      with preoperative HbA1C >=6.5% (0.20 +/- 0.09 vs 0.16 +/- 0.07, P < 0.001).
      CONCLUSIONS: Postoperative glycemic variability is associated with MAEs after
      cardiac surgery. Glycemic variability is only measured when the patient leaves
      the intensive care unit, and there is no opportunity to intervene earlier.
      Preoperative HbA1C identifies risk for postoperative glycemic variability and may
      provide a more rational guide for targeting measures to reduce variability.

PMID- 24445630
TI  - Brachial artery catheterization: an assessment of use patterns and associated
      complications.
AB  - BACKGROUND: Although studies have compared safety and outcomes of radial artery
      cannulation with other arterial catheterization locations, there is insufficient
      information describing brachial artery catheterization. In this study, we
      characterized the perioperative use patterns and the complication rates
      associated with brachial arterial catheterization and compared these outcomes
      with radial artery catheterization. METHODS: We performed a retrospective
      analysis of adult patients (age >=18 years) undergoing surgical procedures at an
      academic medical center from January 1, 2008, to December 31, 2011. An
      institutional database containing information on anesthetic care was queried to
      identify all brachial artery catheterizations. Baseline characteristics, details
      relating to the surgical and catheterization procedures, and catheter-related
      complications were collected and compared with a random sample of patients
      receiving radial artery catheterization. RESULTS: We identified 858 patients
      receiving brachial catheterization perioperatively. An additional 3432 patients
      receiving radial catheterization were identified. Patients receiving brachial
      catheterization were more often women, had a lower body mass index, had more
      comorbidities, and had longer anesthetic and catheterization durations. Three
      vascular complications were identified in the cohort receiving brachial artery
      catheterization compared with 1 patient with a peripheral neuropathy in the
      radial artery catheterization cohort (unadjusted complication incidence [95%
      confidence intervals] brachial artery catheterization, 0.35% [0.12%-1.02%] vs
      radial artery catheterization, 0.03% [0.005%-0.16%], respectively; P = 0.030;
      relative risk [95% confidence interval] = 12.0 [1.7-83.4]). There were no
      catheter-related bloodstream infections. CONCLUSIONS: We found that brachial
      artery catheterization is used in more medically complex patients and for longer
      duration than radial artery catheterizations. Although the limited number of
      adverse outcomes precluded statistical adjustments in this investigation, the
      observed differences in complication rates between cannulation methods suggest
      that brachial artery catheterization may be a suitable alternative to radial
      artery catheterization in patients with complex medical comorbidities.

PMID- 24445631
TI  - The effect of propofol on intrathecal morphine-induced pruritus and its
      mechanism.
AB  - BACKGROUND: Previous studies have shown that a low dose of propofol IV bolus had
      a beneficial effect on intrathecal morphine-induced pruritus in humans. However,
      its exact mechanism has not been fully understood. In this study, we hypothesized
      that propofol relieved intrathecal morphine-induced pruritus in rats by
      upregulating the expression of cannabinoid-1 (CB[1]) receptors in anterior
      cingulate cortex (ACC). METHODS: Twenty-four Sprague-Dawley rats were divided
      into a control group and 20, 40, 80 MUg/kg morphine groups to create an
      intrathecal morphine-induced scratching model. The effects of propofol on
      intrathecal 40 MUg/kg morphine-induced scratching responses were then evaluated.
      Sixty rats were randomly assigned to control, normal saline, intralipid, and
      propofol groups, with pruritus behavior observation or killed 8 minutes after
      venous injection of normal saline, intralipid, or propofol, and brain tissues
      were then collected for assay. Immunohistochemistry was then performed to
      identify the expression of CB (1) receptor in ACC, and the concentration of CB(1)
      receptor in ACC was determined by Western blot analysis. RESULTS: Compared with
      the control group, rats in the 20, 40, 80 MUg/kg morphine groups had higher mean
      scratching response rates after intrathecal morphine injection (P =0.020, 0.005,
      and 0.002, respectively). There was a statistical difference between 20 and 40
      MUg/kg morphine groups at 10 to 15 and 15 to 20 timepoints after intrathecal
      morphine injection (P = 0.049 and 0.017, respectively). Propofol almost abolished
      the scratching response that was induced by 40 MUg/kg intrathecal morphine
      injection (F[2, 15] = 46.87, P < 0.001; F[22, 165] = 2.37, P = 0.001). Compared
      with the intralipid and normal saline groups, the scratching behavior was
      significantly attenuated in the propofol group (P < 0.001). Compared with
      control, normal saline, and intralipid groups, the protein expression of CB(1)
      receptor in ACC (Western blot) in the propofol group increased (0.86 +/- 0.21,
      0.94 +/- 0.18, 0.86 +/- 0.13, and 1.34 +/- 0.32, respectively, P < 0.001). There
      was no significant difference among control, normal saline, and intralipid
      groups. Compared with the control, normal saline, and intralipid groups, the
      average number of neurons of CB(1) receptor in the ACC area were higher in the
      propofol group (21.0 +/- 1.4, 19.3 +/- 1.8, 24.8 +/- 7.7, and 37.2 +/- 3.3,
      respectively, P < 0.001). CONCLUSIONS: Morphine elicits dose-independent
      scratching responses after intrathecal injection in rats. Morphine 40 MUg/kg
      intrathecal injection-induced scratching responses can be prevented by propofol.
      Increased protein expression of CB(1) receptors in ACC may contribute to the
      reversal of intrathecal morphine-induced scratching.

PMID- 24445632
TI  - Emulsified isoflurane increases convulsive thresholds of lidocaine and produces
      neural protection after convulsion in rats.
AB  - BACKGROUND: Local anesthetic-induced convulsions remain a concern of
      anesthesiologists when performing regional anesthesia. Our previous study found
      that the lidocaine requirement for IV regional anesthesia was reduced with
      coadministration of emulsified isoflurane. We designed this study to examine
      whether emulsified isoflurane could increase the convulsive threshold of
      lidocaine and produce protection after a lidocaine-induced convulsion. METHODS:
      In experiment 1, the median convulsive dose of lidocaine with or without the
      addition of emulsified isoflurane was determined using the up-and-down method. In
      experiment 2, emulsified isoflurane (0.032 mL/kg for isoflurane), midazolam (1.6
      mg/kg), 30% Intralipid (solvent of emulsified isoflurane) or saline was infused
      to treat lidocaine-induced convulsions, respectively. Convulsive behavior was
      scored by the modified Racine scale. Cognitive function and the pathology of
      hippocampus cornu ammonis 3 pyramid neurons of rats were evaluated on days 1, 3,
      5, and 7 after convulsions. RESULTS: In experiment 1, the median convulsive dose
      of lidocaine alone producing convulsions was 18.7 +/- 2.6 mg/kg, and it was
      increased to 22.7 +/- 2.6 (P = 0.010) and 26.7 +/- 2.6 mg/kg (P < 0.001) with
      coadministration of emulsified isoflurane at doses of 0.016 and 0.032 mL/kg
      isoflurane, respectively. In experiment 2, both emulsified isoflurane and
      midazolam significantly suppressed lidocaine-induced tonic-clonic seizures. Rats
      treated with emulsified isoflurane regained full consciousness (convulsive score
      = 0) significantly earlier than rats treated with midazolam (8.7 +/- 2.4 vs 19.5
      +/- 3.9 minutes, P < 0.001). Cognitive impairment and hippocampus cornu ammonis 3
      pyramid neuron abnormalities were found after convulsions and improved with the
      administration of both emulsified isoflurane and midazolam. CONCLUSION:
      Emulsified isoflurane increased the convulsive threshold of lidocaine and
      preserved neurological function in rats experiencing lidocaine-induced
      convulsions.

PMID- 24445633
TI  - Up-regulation of NaV1.7 sodium channels expression by tumor necrosis factor-alpha
      in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is not only a key regulator
      of inflammatory response but also an important pain modulator. TNF-alpha enhances
      both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant Na channel
      currents in dorsal root ganglion (DRG) neurons. However, it remains unknown
      whether TNF-alpha affects the function and expression of the TTX-S NaV1.7 Na
      channel, which plays crucial roles in pain generation. METHODS: We used cultured
      bovine adrenal chromaffin cells expressing the NaV1.7 Na channel isoform and
      compared them with cultured rat DRG neurons. The expression of TNF receptor 1 and
      2 (TNFR1 and TNFR2) in adrenal chromaffin cells was studied by Semiquantitative
      reverse transcription-polymerase chain reaction. The effects of TNF-alpha on the
      expression of NaV1.7 were examined with reverse transcription-polymerase chain
      reaction and Western blot analysis. Results were expressed as mean +/- SEM.
      RESULTS: TNFR1 and TNFR2 were expressed in adrenal chromaffin cells, as well as
      reported in DRG neurons. TNF-alpha up-regulated NaV1.7 mRNA by 132% +/- 9% (N =
      5, P = 0.004) in adrenal chromaffin cells, as well as 117% +/- 2% (N = 5, P <
      0.0001) in DRG neurons. Western blot analysis showed that TNF-alpha increased
      NaV1.7 protein up to 166% +/- 24% (N = 5, corrected P < 0.0001) in adrenal
      chromaffin cells, concentration- and time-dependently. CONCLUSIONS: TNF-alpha up
      regulated NaV1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In
      addition, TNF-alpha up-regulated the protein expression of the TTX-S NaV1.7
      channel in adrenal chromaffin cells. Our findings may contribute to understanding
      the peripheral nociceptive mechanism of TNF-alpha.

PMID- 24445635
TI  - Low-dose hydrocortisone therapy attenuates septic shock in adult patients but
      does not reduce 28-day mortality: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The role of low-dose hydrocortisone in attenuating septic shock and
      reducing short-term mortality in adult patients with septic shock is unclear. We
      conducted a meta-analysis of previous studies to determine whether hydrocortisone
      could ameliorate the effects of septic shock at 7 and 28 days and reduce 28-day
      morality. METHODS: Randomized controlled trials (RCTs) of corticosteroids versus
      placebo (or supportive treatment alone) were retrieved from electronic searches
      (Medline, Embase, and Cochrane Library databases; LILACS; and Web of Knowledge)
      and manual searches (up to May 2012). From a pool of 1949 potentially relevant
      articles, duplicate independent review identified 10 relevant, RCTs of low-dose
      hydrocortisone therapy in septic shock. Four pairs of reviewers agreed on the
      criteria for trial eligibility. One reviewer entered the data into the computer,
      and 3 reviewers checked the data. Missing data were obtained from the authors of
      the relevant trials. The primary outcome analyzed was an estimate of 28-day
      mortality. RESULTS: Eight publications were included in the meta-analysis. Low
      dose hydrocortisone therapy did not reduce 28-day mortality (N = 1063; odds ratio
      (OR) = 0.891, 95% confidence interval (CI), 0.69-1.15). Low-dose hydrocortisone
      therapy ameliorated shock at 7 days (6 RCTs, N = 964, OR = 2.078, 95% CI, 1.58
      2.73, P < 0.0001, and I = 26.9%) and 28 days (6 RCTs, N = 947, OR = 1.495, 95%
      CI, 1.12-1.99, P = 0.006, and I = 0.0%). CONCLUSIONS: Although low-dose
      hydrocortisone therapy ameliorates septic shock at 7 and 28 days, it does not
      reduce 28-day mortality.

PMID- 24445634
TI  - Universal intravenous access cleaning device fails to sterilize stopcocks.
AB  - BACKGROUND: Contamination of a central venous catheter may occur through use of
      conventional open-lumen stopcock devices (COLDs), or disinfectable, needleless,
      closed connectors (DNCCs). We investigated the effectiveness of a new universal
      IV access cleaning device (Site-Scrub) compared with 70% isopropyl alcohol prep
      pads for sanitizing COLDs or DNCCs inoculated with common catheter-associated
      pathogens. METHODS: Site-Scrub was compared with 70% alcohol prep pads for
      sanitizing contaminated female Luer lock COLD or DNCC filled with sterile saline
      or propofol and 2 common bacterial central venous catheter contaminants
      (Staphylococcus epidermidis or Pseudomonas aeruginosa). Devices were contaminated
      using a glove touch (COLD and DNCC) or syringe tip (COLD). The primary end point
      of the study was colony-forming units (CFU) after 24 hours. RESULTS: The use of
      glove touch contamination, the contaminants, S epidermidis and P aeruginosa,
      produced CFU in saline-filled COLDs treated with the Site-Scrub, but not in those
      treated with alcohol pads (P < 0.001). Similar results were observed with
      propofol-filled COLDs (P < 0.001). For DNCCs filled with saline or propofol, both
      alcohol and Site-Scrub effectively reduced CFU growth compared with contaminated
      controls (P < 0.001). When COLDs were contaminated by treated syringe tips, there
      was no significant evidence of reduction in CFU growth by using either alcohol
      pads or Site-Scrub compared with contaminated controls. CONCLUSIONS: These data
      suggest that when the inner surface of the COLD is contaminated, both alcohol
      pads and Site-Scrub were not significantly effective in decontaminating the COLD.
      When the COLD rim is contaminated, however, alcohol pads outperform Site-Scrub.
      DNCCs were uniformly decontaminated with either treatment. Future work should
      focus on better access systems because current COLDs are difficult to
      decontaminate.

PMID- 24445636
TI  - What's new in Obstetric Anesthesia? The 2013 Gerard W. Ostheimer lecture.
AB  - The "What's New in Obstetric Anesthesia?" keynote lecture was established by the
      Society for Obstetric Anesthesia and Perinatology in memory of the eminent
      obstetric anesthesiologist, Dr. Gerard W. Ostheimer. From a wide selection of
      journals encompassing the fields of obstetric anesthesia, obstetrics, and
      perinatology, the designated lecturer identifies articles of significant impact
      and interest published in the preceding year. The Ostheimer lecture, delivered
      this year at the annual meeting of the Society in April 2013 in San Juan, Puerto
      Rico, included highly relevant papers that have the potential to change obstetric
      anesthesia practice or impact public health. This review summarizes 5 categories
      of pertinent articles that were published in 2012 and discussed in the 2013
      Ostheimer lecture: maternal diseases, labor and delivery, advances in obstetric
      anesthesia, obstetric complications, and anesthesia-related complications. 

PMID- 24445637
TI  - Anesthetic drugs and onset of malignant hyperthermia.
AB  - BACKGROUND: The time between the beginning of anesthetic administration and
      recognition of the first sign of malignant hyperthermia (MH) (MH onset time)
      could differ among anesthetic drugs. METHODS: We examined the time of the first
      signs of suspected MH, anesthetic drugs administered, subject age, and year of
      event in Adverse Metabolic/Musculoskeletal Reaction to Anesthesia reports in the
      North American Malignant Hyperthermia Registry. Inclusion criteria were judgment
      by the reporting clinician that the event was possible or fulminant MH,
      documentation of the time when anesthetic administration began, and the time when
      the first MH sign was noted. Descriptive statistics, Kruskal-Wallis analysis, and
      nonparametric correlation were used to assess the difference in MH onset times
      under different conditions. RESULTS: Four hundred seventy-seven cases met
      inclusion criteria; 58.5% were possible MH and 41.5% fulminant MH. Inhaled
      anesthetic and succinylcholine were given in 53.9% of cases, inhaled anesthetic
      only in 41.7%, and succinylcholine without inhaled anesthetics in 2.9%. No
      causative anesthetic drugs were reported in 7 MH cases. In 394 patients exposed
      to only 1 of the 4 inhaled anesthetics, without regard for subject age, MH onset
      time was shorter in the presence of halothane than any of the other anesthetics
      and shorter after succinylcholine in all anesthetics. If succinylcholine was not
      given, MH onset was shorter during sevoflurane anesthesia than during desflurane
      or isoflurane. In 322 cases, 1 rather than multiple first signs of MH were
      reported with masseter spasm as the earliest MH sign. In 339 cases in which
      masseter spasm was not reported, there was no difference in MH onset time with or
      without succinylcholine. In 146 cases in which masseter spasm was not reported
      and succinylcholine was not given, MH onset was shorter during halothane
      anesthesia, than during exposure to desflurane, or isoflurane. MH onset time
      during sevoflurane was shorter than during desflurane or isoflurane. MH was
      reported later in the course of anesthesia after 1998, when halothane and
      succinylcholine were less often reported. MH occurred after succinylcholine
      administration in the absence of inhaled anesthetics. We could not separate an
      effect of age from that of other variables. CONCLUSION: The onset of MH has been
      observed later during desflurane and isoflurane anesthesia than during exposure
      to sevoflurane. Since 1998, MH signs have more often appeared later, in the
      second or third hour of anesthesia, than they did before 1998.

PMID- 24445638
TI  - DNA testing for malignant hyperthermia: the reality and the dream.
AB  - The advent of the polymerase chain reaction and the availability of data from
      various global human genome projects should make it possible, using a DNA sample
      isolated from white blood cells, to diagnose rapidly and accurately almost any
      monogenic condition resulting from single nucleotide changes. DNA-based diagnosis
      for malignant hyperthermia (MH) is an attractive proposition, because it could
      replace the invasive and morbid caffeine-halothane/in vitro contracture tests of
      skeletal muscle biopsy tissue. Moreover, MH is preventable if an accurate
      diagnosis of susceptibility can be made before general anesthesia, the most
      common trigger of an MH episode. Diagnosis of MH using DNA was suggested as early
      as 1990 when the skeletal muscle ryanodine receptor gene (RYR1), and a single
      point mutation therein, was linked to MH susceptibility. In 1994, a single point
      mutation in the alpha 1 subunit of the dihydropyridine receptor gene (CACNA1S)
      was identified and also subsequently shown to be causative of MH. In the
      succeeding years, the number of identified mutations in RYR1 has grown, as has
      the number of potential susceptibility loci, although no other gene has yet been
      definitively associated with MH. In addition, it has become clear that MH is
      associated with either of these 2 genes (RYR1 and CACNA1S) in only 50% to 70% of
      affected families. While DNA testing for MH susceptibility has now become
      widespread, it still does not replace the in vitro contracture tests. Whole exome
      sequence analysis makes it potentially possible to identify all variants within
      human coding regions, but the complexity of the genome, the heterogeneity of MH,
      the limitations of bioinformatic tools, and the lack of precise
      genotype/phenotype correlations are all confounding factors. In addition, the
      requirement for demonstration of causality, by in vitro functional analysis, of
      any familial mutation currently precludes DNA-based diagnosis as the sole test
      for MH susceptibility. Nevertheless, familial DNA testing for MH susceptibility
      is now widespread although limited to a positive diagnosis and to those few
      mutations that have been functionally characterized. Identification of new
      susceptibility genes remains elusive. When new genes are identified, it will be
      the role of the biochemists, physiologists, and biophysicists to devise
      functional assays in appropriate systems. This will remain the bottleneck unless
      high throughput platforms can be designed for functional work. Analysis of entire
      genomes from several individuals simultaneously is a reality. DNA testing for MH,
      based on current criteria, remains the dream. 

PMID- 24445639
TI  - The impact of sleep apnea on postoperative utilization of resources and adverse
      outcomes.
AB  - BACKGROUND: Despite the concern that sleep apnea (SA) is associated with
      increased risk for postoperative complications, a paucity of information is
      available regarding the effect of this disorder on postoperative complications
      and resource utilization in the orthopedic population. With an increasing number
      of surgical patients suffering from SA, this information is important to
      physicians, patients, policymakers, and administrators alike. METHODS: We
      analyzed hospital discharge data of patients who underwent total hip or knee
      arthroplasty in approximately 400 U.S. Hospitals between 2006 and 2010. Patient,
      procedure, and health care system-related demographics and outcomes such as
      mortality, complications, and resource utilization were compared among groups.
      Multivariable logistic regression models were fit to assess the association
      between SA and various outcomes. RESULTS: We identified 530,089 entries for
      patients undergoing total hip and knee arthroplasty. Of those, 8.4% had a
      diagnosis code for SA. In the multivariate analysis, the diagnosis of SA emerged
      as an independent risk factor for major postoperative complications (OR 1.47; 95%
      confidence interval [CI], 1.39-1.55). Pulmonary complications were 1.86 (95% CI,
      1.65-2.09) times more likely and cardiac complications 1.59 (95% CI, 1.48-1.71)
      times more likely to occur in patients with SA. In addition, SA patients were
      more likely to receive ventilatory support, use more intensive care, stepdown and
      telemetry services, consume more economic resources, and have longer lengths of
      hospitalization. CONCLUSIONS: The presence of SA is a major clinical and economic
      challenge in the postoperative period. More research is needed to identify SA
      patients at risk for complications and develop evidence-based practices to aid in
      the allocation of clinical and economic resources.

PMID- 24445640
TI  - Prediction of intraoperative transfusion requirements during orthotopic liver
      transplantation and the influence on postoperative patient survival.
AB  - BACKGROUND: Predicting blood product transfusion requirements during orthotopic
      liver transplantation (OLT) remains difficult. Our primary aim in this study was
      to determine which patient variables best predict recipient risk for large blood
      transfusion requirements during OLT. The secondary aim was to determine whether
      the amount of blood products transfused during OLT impacted patient survival.
      METHODS: Eight hundred four primary adult OLTs performed during a 9-year period
      were retrospectively analyzed, and predictive models were developed for blood
      product usage, usage >20 and usage >30 units of red blood cells (RBCs) plus cell
      salvage (CS). For survival analysis, potential predictors included all blood
      products administered during OLT. RESULTS: For analyses of RBC + CS usage, we
      used several statistical techniques: regression analysis, logistic regression,
      and classification and regression tree analysis. Several preoperative factors
      were highly statistically significant predictors of intraoperative blood product
      usage in each of the analyses, namely lower platelet count and higher Model for
      End-Stage Liver Disease Score or one or more of its components (creatinine, total
      bilirubin, international normalized ratio). Despite these highly significant
      associations, the models were unable to predict reliably that patients might
      require the largest amount of blood products during OLT. For example, the
      classification and regression tree analyses were able to predict only 32% and 11%
      of patients requiring >20 and >30 units of RBC + CS, respectively. Survival
      analysis demonstrated poorer survival among patients receiving larger amounts of
      RBC + CS during OLT. CONCLUSION: Prediction of intraoperative blood product
      requirements based on preoperatively available variables is unreliable; however,
      there is a strong measurable association between transfusion and postoperative
      mortality.

PMID- 24445641
TI  - Alternate methods to teach history of anesthesia.
AB  - Residency programs in anesthesiology in the United States struggle to balance the
      conflicting needs of formal didactic sessions, clinical teaching, and clinical
      service obligations. As a consequence of the explosion in knowledge about basic
      and applied sciences related to our specialty, residents and fellows are expected
      to make substantial efforts to supplement formal lectures with self-study. There
      is strong evidence to suggest that members of the younger generation use
      nontraditional methods to acquire information. Although training programs are not
      required to include topics related to history of anesthesia (HOA) in the didactic
      curriculum, and despite the fact that such knowledge does not directly impact
      clinical care, many programs include such lectures and discussions. We describe
      and discuss our experience with 3 alternate modalities of teaching HOA.First, we
      provide brief descriptions of HOA-related historical narratives and novels within
      the domain of popular literature, rather than those that might be considered
      textbooks. Second, we analyze content in movies and videodiscs dealing with HOA
      and determine their utility as educational resources. Third, we describe HOA
      tours to sites in close proximity to our institutions, as well as those in
      locations elsewhere in the United States and abroad.We suggest that informal HOA
      teaching can be implemented by every residency program without much effort and
      without taking away from the traditional curriculum. Participating in this unique
      and enriching experience may be a means of academic advancement. It is our hope
      and expectation that graduates from programs that incorporate such exposure to
      HOA become advocates of history and may choose to devote a part of their academic
      career toward exploration of HOA. 

PMID- 24445642
TI  - The case for collaboration among humanitarian surgical programs in low resource
      countries.

PMID- 24445643
TI  - Transversus abdominis plane block to ameliorate postoperative pain outcomes after
      laparoscopic surgery: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Transversus abdominis plane (TAP) block has been used as a multimodal
      strategy to optimize postoperative pain outcomes; however, it remains unclear
      which type of surgical procedures can benefit from the administration of a TAP
      block. Several studies have examined the effect of the TAP block on postoperative
      pain outcomes after laparoscopic surgical procedures and generated conflicting
      results. Our main objective in the current investigation was to evaluate the
      effect of TAP block on postoperative analgesia outcomes for laparoscopic surgical
      procedures. METHODS: A search was performed to identify randomized controlled
      trials that evaluated the effects of the TAP block compared with an inactive
      group (placebo or "no treatment") on postoperative pain outcomes in laparoscopic
      surgical procedures. Primary outcomes included early (0-4 hours) and late (24
      hours) postoperative pain at rest and on movement and postoperative opioid
      consumption (up to 24 hours). Meta-analysis was performed using a random-effects
      model. Publication bias was evaluated by examining the presence of asymmetric
      funnel plots using Egger regression test. Meta-regression analysis was performed
      to establish an association between the local anesthetic dose and the evaluated
      outcomes. RESULTS: Ten randomized clinical trials with 633 subjects were included
      in the analysis. The weighted mean difference (99% confidence interval) of the
      combined effects favored TAP block over control for pain at rest (<=4 hours, 
      2.41 [-3.6 to -1.16]) and (at 24 hours, -1.33 [-2.19 to -0.48]) (0-10 numerical
      scale). Postoperative opioid consumption was decreased in the TAP block group
      compared with control, weighted mean difference (99% confidence interval) of 
      5.74 (-8.48 to -2.99) mg morphine IV equivalents. Publication bias was not
      present in any of the analysis. Preoperative TAP block administration resulted in
      greater effects on early pain and opioid consumption compared with postoperative
      administration. Meta-regression analysis revealed an association between local
      anesthetic dose and the TAP block effect on late pain at rest and postoperative
      opioid consumption. None of the studies reported symptoms of local anesthetic
      toxicity. CONCLUSIONS: TAP block is an effective strategy to improve early and
      late pain at rest and to reduce opioid consumption after laparoscopic surgical
      procedures. In contrast, the TAP block was not superior compared with control to
      reduce early and late pain during movement. Preoperative administration of a TAP
      block seems to result in greater effects on postoperative pain outcomes. We also
      detected a local anesthetic dose response on late pain and postoperative opioid
      consumption.

PMID- 24445644
TI  - Locally injected dexmedetomidine inhibits carrageenin-induced inflammatory
      responses in the injected region.
AB  - BACKGROUND: Dexmedetomidine, a highly selective agonist of alpha2-adrenoceptors,
      is a commonly used sedative; however, a potent anti-inflammatory effect has also
      been found. In the present study we evaluated the inhibitory effect of locally
      injected dexmedetomidine on inflammatory responses in the injected region.
      METHODS: Local inflammation was induced in the hindpaws of male mice (aged 6-8
      weeks) by intraplantar injection of lambda-carrageenin. To offset the central
      effect of tested agents, different agents were blindly injected into the left and
      right paws in the pairs of comparison. The effect of dexmedetomidine on edema
      (increase in paw volume), the accumulation of leukocytes, and production of tumor
      necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX-2) were evaluated
      after carrageenin injection, using water displacement plethysmometry,
      histological imaging, immunohistochemistry, and Western blotting analysis.
      Furthermore, we also evaluated the effect of yohimbine, a full antagonist of
      alpha2-adrenoceptors, and phenylephrine, an agonist of the alpha1-adrenoceptor,
      on dexmedetomidine's action on inflammatory responses. RESULTS: Paw volume and
      amount of leukocytes in the injected region significantly increased after the
      injection of carrageenin. Similarly, TNF-alpha and COX-2 production was found in
      the subcutaneous region injected with carrageenin, 4 hours after injection.
      Dexmedetomidine significantly inhibited all increases in paw volume, leukocytes,
      and production of TNF-alpha and COX-2. Furthermore, yohimbine significantly
      antagonized the anti-inflammatory effects of dexmedetomidine, whereas
      phenylephrine did not significantly alter them. CONCLUSIONS: The findings suggest
      that locally injected dexmedetomidine exhibits an anti-inflammatory effect
      against local acute inflammatory responses, mediated by alpha2-adrenoceptors.

PMID- 24445645
TI  - Perioperative calibration of noninvasive hemoglobin monitoring.

PMID- 24445646
TI  - In response.

PMID- 24445647
TI  - In response.

PMID- 24445648
TI  - Anesthesiology resident burnout-an Irish perspective.

PMID- 24445649
TI  - In response.

PMID- 24445650
TI  - Hypnotic effect of propofol and hypothalamic nuclei: are we barking up the right
      neurocircuitry?

PMID- 24445651
TI  - In response.

PMID- 24445652
TI  - Capnometry versus acoustic device for monitoring respiration.

PMID- 24445653
TI  - In response.

PMID- 24445654
TI  - Emerging roles of radioresistance in prostate cancer metastasis and radiation
      therapy.
AB  - Radiation therapy (RT) continues to be one of the most popular treatment options
      for localized prostate cancer (CaP). Local CaP recurrence after RT is a pattern
      of treatment failure attributable to radioresistance of cancer cells. One major
      obstacle to RT is that there is a limit to the amount of radiation that can be
      safely delivered to the target organ. Recent results indicate that
      phosphoinositide 3-kinase (PI3K)/Akt/phosphatase and tensin homolog
      (PTEN)/mammalian target of rapamycin (mTOR) signaling pathway, autophagy,
      epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are involved
      in CaP metastasis and radioresistance. Emerging evidence also suggests that
      combining a radiosensitizer with RT increases the efficacy of CaP treatment.
      Understanding the mechanisms of radioresistance will help to overcome recurrence
      after RT in CaP patients and prevent metastasis. In this review, we discuss the
      novel findings of PI3K/Akt/PTEN/mTOR signaling pathway, autophagy, EMT and CSCs
      in the regulation of CaP metastasis and radioresistance, and focus on combination
      of radiosensitizers with RT in the treatment of CaP in preclinical studies to
      explore novel approaches for future clinical trials. 

PMID- 24445655
TI  - Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and
      biofuel production.
AB  - Economic feasibility of biosynthetic fuel and chemical production hinges upon
      harnessing metabolism to achieve high titre and yield. Here we report a thorough
      genotypic and phenotypic optimization of an oleaginous organism to create a
      strain with significant lipogenesis capability. Specifically, we rewire Yarrowia
      lipolytica's native metabolism for superior de novo lipogenesis by coupling
      combinatorial multiplexing of lipogenesis targets with phenotypic induction. We
      further complete direct conversion of lipid content into biodiesel. Tri-level
      metabolic control results in saturated cells containing upwards of 90% lipid
      content and titres exceeding 25 g l(-1) lipids, which represents a 60-fold
      improvement over parental strain and conditions. Through this rewiring effort, we
      advance fundamental understanding of lipogenesis, demonstrate non-canonical
      environmental and intracellular stimuli and uncouple lipogenesis from nitrogen
      starvation. The high titres and carbon-source independent nature of this
      lipogenesis in Y. lipolytica highlight the potential of this organism as a
      platform for efficient oleochemical production. 

PMID- 24445656
TI  - The effect of glargine versus glimepiride on pancreatic beta-cell function in
      patients with type 2 diabetes uncontrolled on metformin monotherapy: open-label,
      randomized, controlled study.
AB  - The aim of present study is to assess whether if basal insulin, glargine, could
      improve insulin secretory function of beta-cells compared with glimepiride when
      metformin alone was failed. This was an open-label and multi-center study for 52
      weeks in Korean patients with uncontrolled type 2 diabetes by metformin
      monotherapy. Subjects were randomized to glargine or glimepiride groups (n = 38
      vs. 36, respectively). The primary endpoint was to compare changes in c-peptide
      via glucagon test after 48 weeks. Glycemic efficacy and safety endpoints
      (glycated hemoglobin (HbA1c), HOMA-B, fasting plasma glucose (FPG), lipid
      profiles, and hypoglycemic events) were also checked. The mean disease duration
      of all subjects was 88.2 months. Changes in C-peptide was no significant
      different between groups (P = 0.73), even though insulin secretion was not
      worsened in both groups at the endpoint. Glargine was not superior to glimepiride
      in other beta-cell function indexes such as HOMA-B (P = 0.28). HbA1c and FPG
      reduced significantly in each groups but not different between two groups.
      Although, severe hypoglycemia did not occur, symptomatic hypoglycemia was more
      frequent in glimepiride group (P = 0.01). Insulin glargine was as effective as
      glimepiride in controlling hyperglycemia and maintaining beta-cell function in
      Korean patients with type 2 diabetes during 48 weeks study period, after failure
      of metformin monotherapy. Hypoglycemic profile was favorable in the insulin
      glargine group and less weight gain was observed in the glimepiride group. Our
      results suggest that glargine and glimepiride can be considered after failure of
      metformin monotherapy.

PMID- 24445657
TI  - [Partial breast irradiation].
AB  - Owing to breast cancer screening, breast cancer is more and more diagnosed at
      early stage. For those breast cancer women, breast conserving treatment (breast
      conserving surgery followed by whole breast irradiation) is commonly used since
      many years. New radiation modalities have been recently developed in early breast
      cancers particularly accelerated partial breast irradiation (APBI). Among all
      techniques of radiotherapy, 3D-conformal APBI and intraoperative radiotherapy
      (IORT) are the main modalities of radiotherapy used. The present review states on
      indications, treatment modalities and updated results of local control and side
      effects of partial breast irradiation. 

PMID- 24445658
TI  - Organocatalytic photoreduction of Zn(II) to zinc metal.
AB  - The photoreduction of Zn(II) to Zn metal catalyzed by 8-hydroxyquinoline
      derivatives is reported. Structure-activity relationships, ideal reaction
      conditions, and the reaction kinetics are described and a mechanism involving an
      in situ formed quinolate complex is portrayed.

PMID- 24445659
TI  - Contrasting trends in light pollution across Europe based on satellite observed
      night time lights.
AB  - Since the 1970s nighttime satellite images of the Earth from space have provided
      a striking illustration of the extent of artificial light. Meanwhile, growing
      awareness of adverse impacts of artificial light at night on scientific
      astronomy, human health, ecological processes and aesthetic enjoyment of the
      night sky has led to recognition of light pollution as a significant global
      environmental issue. Links between economic activity, population growth and
      artificial light are well documented in rapidly developing regions. Applying a
      novel method to analysis of satellite images of European nighttime lights over 15
      years, we show that while the continental trend is towards increasing brightness,
      some economically developed regions show more complex patterns with large areas
      decreasing in observed brightness over this period. This highlights that
      opportunities exist to constrain and even reduce the environmental impact of
      artificial light pollution while delivering cost and energy-saving benefits. 

PMID- 24445661
TI  - UV-Vis reflection spectroscopy under variable angle incidence at the air-liquid
      interface.
AB  - The UV-Vis reflection spectroscopy (UV-Vis-RS) in situ at the air-liquid
      interface provides information about tilt and aggregation of chromophores in
      Langmuir monolayers. This information is particularly important given in most
      cases the chromophore is located at the polar region of the Langmuir monolayer.
      This region of the Langmuir monolayers has been hardly accessible by other
      experimental techniques. In spite of its enormous potential, the application of
      UV-Vis-RS has been limited mainly to reflection measurements under light normal
      incidence or at lower incidence angles than the Brewster angle. Remarkably, this
      technique is quite sensitive to the tilt of the chromophores at values of
      incidence angles close to or larger than the Brewster angle. Therefore, a novel
      method to obtain the order parameter of the chromophores at the air-liquid
      interface by using s- and p-polarized radiation at different incidence angles is
      proposed. This method allowed for the first time the experimental observation of
      the two components with different polarization properties of a single UV-Vis band
      at the air-liquid interface. The method of UV-Vis spectroscopy under variable
      angle incidence is presented as a new tool for obtaining rich detailed
      information on Langmuir monolayers. 

PMID- 24445660
TI  - Adipocyte fatty acid-binding protein is released from adipocytes by a non
      conventional mechanism.
AB  - Adipocyte fatty acid-binding protein (AFABP) is an adipokine, which induces
      insulin resistance. However, AFABP does not possess any secretion-directed
      signals and the mechanisms for AFABP release have not been thoroughly assessed so
      far. In the current study, mechanisms for AFABP secretion were elucidated in 3T3
      L1 adipocytes in vitro in the presence or absence of hormonal stimulation,
      calcium ionophore and secretion inhibitors by cell fractionation experiments,
      immunoblotting and ELISAs. We demonstrate that AFABP secretion is upregulated
      during adipocyte differentiation. AFABP secretion is not influenced by treatment
      with protein secretion inhibitors that block vesicular traffic at the endoplasmic
      reticulum and the Golgi apparatus. AFABP is secreted partially by adipocyte
      derived microvesicles (ADMs), an established mechanism for unconventional
      secretion from adipocytes. Both total and ADM-secreted AFABP are downregulated by
      insulin and upregulated by the calcium ionophore ionomycin. Furthermore, murine
      RAW 264.7 macrophages secrete AFABP and AFABP release from these cells is
      upregulated by lipopolysaccharide treatment. Taken together, these results
      suggest that AFABP is actively released by unconventional mechanisms and by ADMs
      from 3T3-L1 adipocytes. Furthermore, AFABP secretion from fat cells is regulated
      by insulin and intracellular calcium. 

PMID- 24445662
TI  - Magnetoelectric Fe2TeO6 thin films.
AB  - We demonstrate that Fe2TeO6 is a magnetoelectric antiferromagnet with voltage
      controllable boundary magnetization. This provides experimental evidence of the
      theoretical prediction that boundary magnetization is a universal property of
      magnetoelectric antiferromagnets including boundary magnetization at a surface
      orthogonal to the polar direction. Highly (110) textured Fe2TeO6 thin films were
      grown by pulsed laser deposition, terminating in Te-O at the (110) surface due to
      a surface reconstruction. Magnetic dc susceptibility measurements of both Fe2TeO6
      powder and thin film samples confirm antiferromagnetic long-range order. Finally,
      measurements of x-ray magnetic circular dichroism combined with photoemission
      electron microscopy (XMCD-PEEM) provide a lower bound to the spin and angular
      magnetic moment of the surface Fe ions.

PMID- 24445663
TI  - Deproto-metallation using a mixed lithium-zinc base and computed CH acidity of 1
      aryl 1H-benzotriazoles and 1-aryl 1H-indazoles.
AB  - 1-Aryl-1H-benzotriazoles and -1H-indazoles were synthesized, and their deproto
      metallation using the base prepared by mixing LiTMP with ZnCl2.TMEDA (1/3 equiv.)
      was studied. In the indazole series, reactions occurring at the 3 position were
      followed by ring opening, and functionalization of the substrate was only found
      possible (on the sulfur ring) using 2-thienyl as aryl group. In the benzotriazole
      series, either mono- or bis-deprotonation (depending on the amount of base
      employed) was achieved with phenyl, 4-methoxyphenyl and 2-thienyl as aryl group,
      and bis-deprotonation in the case of 4-chlorophenyl and 4-trifluoromethylphenyl.
      The experimental results were analyzed with the help of the CH acidities of the
      substrates, determined in THF solution using the DFT B3LYP method. 

PMID- 24445664
TI  - Autoimmunity: a new clue to sleepiness.

PMID- 24445665
TI  - The function of Fcgamma receptors in dendritic cells and macrophages.
AB  - Dendritic cells (DCs) and macrophages use various receptors to recognize foreign
      antigens and to receive feedback control from adaptive immune cells. Although it
      was long believed that all immunoglobulin Fc receptors are universally expressed
      by phagocytes, recent findings indicate that only monocyte-derived DCs and
      macrophages express high levels of activating Fc receptors for IgG (FcgammaRs),
      whereas conventional and plasmacytoid DCs express the inhibitory FcgammaR. In
      this Review, we discuss how the uptake, processing and presentation of antigens
      by DCs and macrophages is influenced by FcgammaR recognition of immunoglobulins
      and immune complexes in the steady state and during inflammation. 

PMID- 24445669
TI  - US budget bill includes modest boost to NIH funding.

PMID- 24445668
TI  - Validation of the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor
      Impact Questionnaire (PFIQ-7) in a Dutch population.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to validate the
      Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire
      (PFIQ-7) in Dutch women. METHODS: Patients with pelvic floor dysfunction
      completed the Dutch questionnaires at (1) inclusion to evaluate internal
      consistency, (2) 1 week later to assess test-retest reliability, and (3) 6 months
      later to assess responsiveness and interpretability of change. To assess
      validity, floor and ceiling effects and construct validity were tested. A
      population-based sample (reference group) completed the questionnaires once.
      RESULTS: Data of 111 patients and 283 reference group participants were analyzed.
      Internal consistency of baseline scores in patient and reference groups was
      moderate (Cronbach's alpha 0.52-0.60) to adequate in the PFDI-20 (Cronbach's
      alpha 0.71-0.84) and adequate in the PFIQ-7 (Cronbach's alpha 0.88-0.94). Both
      measures presented adequate test-retest reliability (intraclass correlation
      coefficient 0.79-0.91) and adequate responsiveness (area under the receiver
      operating characteristic curve both 0.77). Interpretability was adequate for PFDI
      20 and acceptable for PFIQ-7 with a clinically relevant minimally important
      change of -23 and -29 points, respectively. At baseline, the scales of the PFIQ-7
      showed floor effects (44-55 %) in patients, though the PFIQ-7 summary score did
      not. No ceiling effects were observed. Construct validity was adequate with all
      predefined hypotheses confirmed regarding subgroup discrimination using pooled
      patient and reference group baseline data. CONCLUSIONS: For assessing distress
      and health-related quality of life of pelvic floor dysfunction, the Dutch PFDI-20
      and PFIQ-7 are reliable and valid in the general Dutch population, and also
      responsive and interpretable among tertiary care-seeking women.

PMID- 24445666
TI  - Alveolar macrophages: plasticity in a tissue-specific context.
AB  - Alveolar macrophages exist in a unique microenvironment and, despite historical
      evidence showing that they are in close contact with the respiratory epithelium,
      have until recently been investigated in isolation. The microenvironment of the
      airway lumen has a considerable influence on many aspects of alveolar macrophage
      phenotype, function and turnover. As the lungs adapt to environmental challenges,
      so too do alveolar macrophages adapt to accommodate the ever-changing needs of
      the tissue. In this Review, we discuss the unique characteristics of alveolar
      macrophages, the mechanisms that drive their adaptation and the direct and
      indirect influences of epithelial cells on them. We also highlight how airway
      luminal macrophages function as sentinels of a healthy state and how they do not
      respond in a pro-inflammatory manner to antigens that do not disrupt lung
      structure. The unique tissue location and function of alveolar macrophages
      distinguish them from other macrophage populations and suggest that it is
      important to classify macrophages according to the site that they occupy. 

PMID- 24445670
TI  - Computed tomography automatic exposure control techniques in 18F-FDG oncology PET
      CT scanning.
AB  - OBJECTIVES: Computed tomography (CT) automatic exposure control (AEC) systems are
      now used in all modern PET-CT scanners. A collaborative study was undertaken to
      compare AEC techniques of the three major PET-CT manufacturers for fluorine-18
      fluorodeoxyglucose half-body oncology imaging. MATERIALS AND METHODS: An audit of
      70 patients was performed for half-body CT scans taken on a GE Discovery 690,
      Philips Gemini TF and Siemens Biograph mCT (all 64-slice CT). Patient demographic
      and dose information was recorded and image noise was calculated as the SD of
      Hounsfield units in the liver. A direct comparison of the AEC systems was made by
      scanning a Rando phantom on all three systems for a range of AEC settings.
      RESULTS: The variation in dose and image quality with patient weight was
      significantly different for all three systems, with the GE system showing the
      largest variation in dose with weight and Philips the least. Image noise varied
      with patient weight in Philips and Siemens systems but was constant for all
      weights in GE. The z-axis mA profiles from the Rando phantom demonstrate that
      these differences are caused by the nature of the tube current modulation
      techniques applied. The mA profiles varied considerably according to the AEC
      settings used. CONCLUSION: CT AEC techniques from the three manufacturers yield
      significantly different tube current modulation patterns and hence deliver
      different doses and levels of image quality across a range of patient weights.
      Users should be aware of how their system works and of steps that could be taken
      to optimize imaging protocols.

PMID- 24445667
TI  - The roles of Pellino E3 ubiquitin ligases in immunity.
AB  - Pellino proteins were initially characterized as a family of E3 ubiquitin ligases
      that can catalyse the ubiquitylation of interleukin-1 receptor-associated kinase
      1 (IRAK1) and regulate innate immune signalling pathways. More recently,
      physiological and molecular roles for members of the Pellino family have been
      described in the regulation of innate and adaptive immune responses by
      ubiquitylation. This Review describes the emerging roles of Pellino proteins in
      innate and adaptive immunity and discusses the mechanistic basis of these
      functions. 

PMID- 24445671
TI  - Natural folates from biofortified tomato and synthetic 5-methyl-tetrahydrofolate
      display equivalent bioavailability in a murine model.
AB  - Folate deficiency is a global health problem related to neural tube defects,
      cardiovascular disease, dementia, and cancer. Considering that folic acid (FA)
      supply through industrialized foods is the most successful intervention,
      limitations exist for its complete implementation worldwide. Biofortification of
      plant foods, on the other hand, could be implemented in poor areas as a
      complementary alternative. A biofortified tomato fruit that accumulates high
      levels of folates was previously developed. In this study, we evaluated short
      term folate bioavailability in rats infused with this folate-biofortified fruit.
      Fruit from tomato segregants hyperaccumulated folates during an extended ripening
      period, ultimately containing 3.7-fold the recommended dietary allowance in a 100
      g portion. Folate-depleted Wistar rats separated in three groups received a
      single dose of 1 nmol of folate/g body weight in the form of lyophilized
      biofortified tomato fruit, FA, or synthetic 5-CH3-THF. Folate bioavailability
      from the biofortified tomato was comparable to that of synthetic 5-CH3-THF, with
      areas under the curve (AUC(0-infinity)) of 2,080 +/- 420 and 2,700 +/- 220 pmol .
      h/mL, respectively (P = 0.12). Whereas, FA was less bioavailable with an AUC(0
      infinity) of 750 +/- 10 pmol . h/mL. Fruit-supplemented animals reached maximum
      levels of circulating folate in plasma at 2 h after administration with a
      subsequent steady decline, while animals treated with FA and synthetic 5-CH3-THF
      reached maximum levels at 1 h. Pharmacokinetic parameters revealed that
      biofortified tomato had slower intestinal absorption than synthetic folate forms.
      This is the first study that demonstrates the bioavailability of folates from a
      biofortified plant food, showing its potential to improve folate deficiency.

PMID- 24445672
TI  - Effect of betulin-containing extract from birch tree bark on alpha-amylase
      activity in vitro and on weight gain of broiler chickens in vivo.
AB  - In vitro effect of betulin-containing extract from Betula pendula Roth. bark on
      alpha-amylase activity was studied, the kinetic mechanism of interaction was
      proposed and in vivo effect of betulin-containing extract on weight gain and meat
      quality of broiler chickens was evaluated. The highest level of inhibitory
      activity (20%) was detected in extract concentration of 1,000 mg/L. Increased
      extract concentration did not lead to increased enzyme inhibition. Using Dixon
      and Cornish-Bowden coordinates, the competitive mechanism of inhibition was
      demonstrated. Calculated kinetic parameters were: Km equal to 0.6 mg/mL, Vmax
      equal to 2.6 and 2.1 mM/min from Lineweaver-Burk and Dixon coordinates,
      respectively and Ki equal to 3,670 +/- 230 mg/mL. The partial inhibition of
      enzyme indicates the existence of low concentration of active inhibitory form,
      which reaches saturation level with increased extract concentration in applied
      suspension. Therefore, Ki has an apparent constant character. This partial
      inhibition of amylase activity observed in in vitro assay did not affect weight
      gain and meat quality of broiler chickens during in vivo assay. Rather, the
      tendency to increase the weight of edible parts and muscles compared to diet
      without additive suggests that the extract may be a potential food additive in
      poultry farming. Additionally, it could be a source for further pharmaceutical
      and pharmacological research.

PMID- 24445673
TI  - The short- and long-term outcomes of laparoscopic versus open surgery for
      colorectal cancer: a meta-analysis.
AB  - PURPOSE: The aim of the study was to compare short- and long-term outcomes of
      laparoscopic surgery and conventional open surgery for colorectal cancer.
      METHODS: Published randomized controlled trial (RCT) reports of laparoscopic
      surgery and open surgery for colorectal cancer were searched, and short- and long
      term factors were extracted to perform meta-analysis. RESULTS: A total of 15 RCT
      reports (6,557 colorectal cancer patients) were included in this study. Blood
      loss of laparoscopic surgery was less by 91.06 ml than open surgery (p = 0.044).
      Operation time was longer by 49.34 min (p = 0.000). The length of hospital stay
      was shorter by 2.64 days (p = 0.003). Incisional length was shorter by 9.23 cm (p
      = 0.000). Fluid intake was shorter by 0.70 day (p = 0.001). Bowel movement was
      earlier by 0.95 day (p = 0.000). Incidence of complications, blood transfusion,
      and 30 days death were significantly lower in laparoscopic surgery than in open
      surgery (p = 0.011, 0.000, 0.01). But there was no significant difference in
      lymph nodes (p = 0.535) and anastomotic leak (p = 0.924). There was also no
      significant difference in 3 and 5 years overall survival (p = 0.298, 0.966),
      disease-free survival (p = 0.487, 0.356), local recurrence (p = 0.270, 0.649),
      and no difference in 5 years distant recurrence (p = 0.838). CONCLUSIONS:
      Laparoscopic surgery is a mini-injured approach which can cure colorectal cancer
      safely and radically, and it is not different from conventional open surgery in
      long-term effectiveness, so laparoscopic surgery can be tried to widely use in
      colorectal cancer.

PMID- 24445674
TI  - Arius of Alexandria (256-336 AD): the first reported mortality from rectal
      prolapse.

PMID- 24445675
TI  - Urinary tract infections in patients with spinal injuries.
AB  - Urinary tract infection remains an important problem for patients with spinal
      cord injury. Interventions used to promote bladder emptying and maintain low
      pressure voiding have variable risks for urinary tract infection. Asymptomatic
      bacteriuria is common in this population and should not be treated. However,
      identification of symptomatic infection is compromised by difficulties in
      ascertainment of symptoms. Use of hydrophilic coated catheters for intermittent
      catheterization does not influence the frequency of symptomatic urinary tract
      infection. Botulinum toxin injection in the detrusor muscle or the urethral
      sphincter improves bladder emptying and does not influence the frequency of
      urinary infection. Asymptomatic bacteriuria is a common finding in pregnant women
      with spinal cord injury, but optimal management is not clear. Other research
      needs include further development and evaluation of interventions to decrease the
      frequency of infection, improve diagnostic precision, and limit the emergence of
      resistant organisms. 

PMID- 24445676
TI  - The right supraclavicular ultrasound view for real-time ultrasound-guided
      definite placement of a central venous catheter with a microconvex transducer.

PMID- 24445677
TI  - Breaking the needle: a rare complication on EZ-IO removal.

PMID- 24445678
TI  - Consumer and family psychoeducation: assessing the evidence.
AB  - OBJECTIVE: Psychoeducation provides adult consumers who have serious mental
      illness or co-occurring substance use disorders with information to support
      recovery. Some models also provide this service to family members. This review
      examined the evidence base for psychoeducation models in group and individual
      formats. METHODS: Authors reviewed meta-analyses, research reviews, and
      individual studies from 1995 through 2012. Databases surveyed were PubMed,
      PsycINFO, Applied Social Sciences Index and Abstracts, Sociological Abstracts,
      Social Services Abstracts, Published International Literature on Traumatic
      Stress, the Educational Resources Information Center, and the Cumulative Index to
      Nursing and Allied Health Literature. Authors chose from three levels of evidence
      (high, moderate, and low) on the basis of benchmarks for the number of studies
      and quality of their methodology. They also described service effectiveness.
      RESULTS: More than 30 randomized controlled trials (RCTs) of consumer
      psychoeducation and more than 100 RCTs of family psychoeducation provide a high
      level of evidence for the effectiveness of each model. Reviews of consumer
      psychoeducation found that experimental groups had reduced nonadherence
      (primarily with medication regimens), fewer relapses, and reduced hospitalization
      rates compared with control groups. Some studies found significant improvements
      in social and global functioning, consumer satisfaction, and quality of life.
      Multifamily psychoeducation groups (the focus of numerous studies) were
      associated with significantly improved problem-solving ability and a reduced
      burden on families, compared with control groups, among other strong outcome
      effects. CONCLUSIONS: Psychoeducation should be included in covered services.
      Group and family interventions are especially powerful. Future research should
      assess psychoeducation models with children and adolescents and with individuals
      from various racial and ethnic backgrounds.

PMID- 24445679
TI  - MafB promotes atherosclerosis by inhibiting foam-cell apoptosis.
AB  - MafB is a transcription factor that induces myelomonocytic differentiation.
      However, the precise role of MafB in the pathogenic function of macrophages has
      never been clarified. Here we demonstrate that MafB promotes hyperlipidemic
      atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is
      predominantly expressed in foam cells found within atherosclerotic lesions, where
      MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis
      inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails
      to induce the expression of AIM, a protein that is normally responsible for
      protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone
      to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells
      in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam
      cell apoptosis, which subsequently led to the attenuation of the early
      atherogenic lesion. These findings represent the first evidence that the
      macrophage-affiliated MafB transcription factor participates in the acceleration
      of atherogenesis. 

PMID- 24445680
TI  - Effect of matrine on primary human hepatocytes in vitro.
AB  - Matrine is a bioactive component of the traditional Chinese medical herb Sophora
      flavescens that has been used in China to treat various kinds of diseases
      including virus hepatitis. However, the molecular mechanisms underlying its
      hepatoprotective effects remains elusive. In the present study, primary human
      hepatocytes were employed to elucidate the protective effects and molecular
      mechanisms of matrine. We observed that low concentrations of matrine had no
      significant impact on albumin secretion, but high concentrations (>140 mg/L) of
      matrine decreased the albumin secretion in hepatocytes. Western blot data
      indicated that matrine at 140 mg/L at 72 h induced protein expression of CYP2A6,
      CYP2B6 and CYP3A4. Furthermore, high concentrations of matrine reduced LDH and
      AST levels and were cytotoxic to hepatocytes, leading to a decreased cell
      viability and total protein amount. Moreover, low concentrations of matrine,
      enhanced the ECOD activity and decreased the level of NO2 (-) induced by
      cytokines in human hepatocytes. Taken together, the present study sheds novel
      light on the molecular mechanisms of matrine and potential application of matrine
      in hepatic diseases. 

PMID- 24445681
TI  - Risk factors for maintenance hemodialysis patients undergoing elective and
      emergency abdominal surgery.
AB  - PURPOSE: To identify the risk factors for morbidity and mortality after elective
      and emergency abdominal surgeries in maintenance hemodialysis patients. METHODS:
      We retrospectively evaluated the medical records of 63 hemodialysis patients who
      underwent elective (group 1) and 24 who underwent emergency (group 2) abdominal
      surgeries, and classified them according to the presence/absence of postoperative
      complications. The clinical, laboratory and procedure-related data were obtained
      and compared between the groups. RESULTS: Group 2 had significantly higher
      morbidity and mortality rates than group 1 (58.3 and 16.6 % vs. 33.3 and 16.6 %,
      respectively, P < 0.05). The patients in group 1 with and without complications
      had significantly different blood urea nitrogen (BUN) levels of 52.3 vs. 41.6
      mg/dL (P = 0.03). There were significant differences in the patients in group 2
      in terms of the age (72.7 vs. 55.0 years old; P < 0.002), the length of the
      operation (141 vs. 107 min; P < 0.02), the total protein levels (6.2 vs. 6.7
      g/dL; P < 0.03), albumin levels (3.2 vs. 3.7 g/dL; P < 0.04) and need for intra-
      or postoperative blood transfusions (71.4 vs. 10.0 %; P < 0.005). CONCLUSIONS:
      The risk factors for a poor surgical outcome included high BUN levels in the
      elective surgery patients and hypoproteinemia, hypoalbuminemia, a longer
      operation and older age in patients undergoing emergency surgery. Perioperative
      blood transfusion was also associated with a high complication rate in the
      emergency surgery group.

PMID- 24445682
TI  - Thoracoscopic versus transsternal resection for early stage thymoma: long-term
      outcomes.
AB  - PURPOSE: This study was undertaken to investigate the efficacy of a video
      assisted thoracoscopic (VATS) approach for stage I and II thymoma through
      comparisons with the transsternal approach. METHODS: The indications for VATS
      resection were clinical stage I or II thymoma, a tumor less than 50 mm, located
      within the thymic lobes and separated from the brachiocephalic vein. Data were
      collected between 1995 and 2007. RESULTS: Twenty-seven patients underwent total
      thymectomy (15 by VATS and 12 by the transsternal approach). The mean tumor size
      was 36.3 (22-50) mm for VATS and 37.6 (15-55) mm for the transsternal group (p =
      0.7862). The mean lengths of the operation were 249.8 min and 227.9 min (p =
      0.2728), respectively. The mean intraoperative blood loss was significantly lower
      in VATS, at 92.3 ml, than the 225.1 ml lost in the transsternal group (p =
      0.0020). The morbidity rates were 13.3 and 8.3% (p = 0.6812), respectively. There
      was no mortality in either group. The mean follow-up periods were 109.0 (37-145)
      months following VATS and 102.0 (44-175) months following the transsternal
      approach. One stage II patient developed pleural dissemination three years after
      VATS resection. Other patients survived with no recurrence. CONCLUSIONS: VATS
      resection of early stage thymoma can be performed with less bleeding and with a
      comparable prognosis to the transsternal approach. VATS resection should thus be
      considered as a viable option for treatment.

PMID- 24445683
TI  - [MET signalling pathway and its therapeutic implications in gastrointestinal
      cancers].
AB  - The MET receptor tyrosine kinase and its ligand HGF regulates many signalling
      pathways involved in proliferation and cell motility, invasion and angiogenesis.
      Deregulation of HGF-MET system by different biological mechanisms may contribute
      to the tumour development in many types of cancers. Some pharmacological
      approaches have been developed to inhibit the HGF-MET signalling pathway, using
      monoclonal antibodies against HGF or MET, or using tyrosine kinase inhibitors of
      MET receptor. In digestive cancers, several clinical studies have evaluated the
      safety and efficacy of these targeted therapies, with some promising results but
      requiring confirmation in phase III trials. Moreover, it appears that MET tumour
      expression could be a predictive marker of response to these targeted therapies
      for some gastrointestinal tumours. Thus, somatic alterations in HGF-MET system
      may represent interesting therapeutic targets and help to select patients who can
      favourably respond to such targeted treatment. 

PMID- 24445684
TI  - Porous organic polymers with anchored aldehydes: a new platform for post
      synthetic amine functionalization en route for enhanced CO2 adsorption
      properties.
AB  - A novel porous organic polymer has been synthesized using the molecular building
      block approach to deliberately encompass aldehyde functionalities amenable to
      post functionalization. The resultant porous framework allows a facile, one-step
      quantitative and post-synthetic functionalization by amines, permitting enhanced
      CO2 sorption properties. 

PMID- 24445685
TI  - N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances:
      a randomized, double-blinded, placebo-controlled, clinical trial.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of oral n-acetyl
      cysteine, as a potential nephroprotective agent, in preventing and/or attenuating
      amphotericin B-induced electrolytes imbalances. METHODS: During a one year
      period, patients were to receive conventional amphotericin b for any indication
      for at least one week and were randomly allocated to receive either placebo or
      600 mg oral n-acetyl cysteine twice daily during the treatment course of
      amphotericin b. Demographic and clinical data of the study population were
      gathered. Different aspects of amphotericin b nephrotoxicity including decrease
      of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and
      potassium wasting were assessed. Each patient was monitored for any adverse
      reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine
      and placebo groups completed the study, 3incidences of hypokalemia (75 % versus
      70 %; P = 0.724) and hypomagnesemia (30 % versus 20 %; P = 0.468) did not differ
      significantly between placebo and NAC groups, respectively. Although the rate of
      AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus
      40 %), this difference was not statistically significant (P = 0.209) even after
      adjusting for probable associated factors of amphotericin b nephrotoxicity (P =
      0.206). The incidence as well as time of onset of electrolyte abnormalities also
      did not differ significantly between placebo and n-acetyl cysteine groups. About
      44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild
      unpleasant taste during the study. CONCLUSION: Oral n-acetyl cysteine during the
      amphotericin B treatment course was not significantly effective in preventing or
      mitigating different features of its nephrotoxicity including decrease of
      glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as
      well as magnesium wasting.

PMID- 24445686
TI  - Association between an excess risk of acute kidney injury and concomitant use of
      ibuprofen and acetaminophen in children, retrospective analysis of a spontaneous
      reporting system.
AB  - PURPOSE: Ibuprofen and acetaminophen are frequently alternated or simultaneously
      used to treat fever or pain in children, while the evidence for the safety of
      such a combination is lacking. In this study, we analyzed the association of
      acute kidney injury (AKI) with ibuprofen, acetaminophen, and the combination of
      both drugs in children (0-12 years) by using the FDA Adverse Event Reporting
      System (AERS) database between January 2004 and June 2012. METHODS: Adverse event
      reports in children aged 0 to <=12 years were included in the study. Cases were
      defined as reports of AKI according to the Medical Dictionary for Regulatory
      Activities (MedDRA) terminology, non-cases as all other reports. Exposure
      categories were divided into three index groups: two groups where ibuprofen or
      acetaminophen were used in absence of one another and another group where both
      drugs were used concomitantly. There was also a reference group, in which neither
      ibuprofen nor acetaminophen was used. These index groups were compared with the
      reference group using reporting odds ratios (RORs). RESULTS: In total, 47,803
      reports were included in the study. After adjusting for year of reporting, age,
      and sex, the ROR for an AKI in children who used only ibuprofen or acetaminophen
      compared with children who used neither ibuprofen nor acetaminophen was 2.14 (95
      % CI: 1.59-2.88) and 1.53 (95 % CI: 1.18-1.97), respectively, while the adjusted
      ROR was 4.01 (95 % CI: 2.96-5.43) when both drugs were concomitantly used.
      CONCLUSIONS: The results illustrate that the concomitant use of ibuprofen and
      acetaminophen in children might be associated with increased risk of AKI.

PMID- 24445689
TI  - Micro-battery development for juvenile salmon acoustic telemetry system
      applications.
AB  - The Endangered Species Act requires actions that improve the passage and survival
      rates for migrating salmonoids and other fish species that sustain injury and
      mortality when passing through hydroelectric dams. To develop a low-cost
      revolutionary acoustic transmitter that may be injected instead of surgically
      implanted into the fish, one major challenge that needs to be addressed is the
      micro-battery power source. This work focuses on the design and fabrication of
      micro-batteries for injectable fish tags. High pulse current and required service
      life have both been achieved as well as doubling the gravimetric energy density
      of the battery. The newly designed micro-batteries have intrinsically low
      impedance, leading to significantly improved electrochemical performances at low
      temperatures as compared with commercial SR416 batteries. Successful field trial
      by using the micro-battery powered transmitters injected into fish has been
      demonstrated, providing an exemplary model of transferring fundamental research
      into practical devices with controlled qualities. 

PMID- 24445690
TI  - On the inter-ring torsion potential of regioregular P3HT: a first principles
      reexamination with explicit side chains.
AB  - Poly(3-alkylthiophene) is a family of conjugated semicrystalline polymers for
      organic electronic applications. Crucial for the fine-tuning of such systems is a
      detailed understanding of the correlation between molecular structure/morphology
      and electronic properties. However, a series of a priori assumptions is commonly
      made in order to deduce macromolecular-scale geometric and energetic features
      from those of rather small homologous molecular systems. Alkyl side chains are
      routinely shortened (if not systematically removed) during such high-accuracy ab
      initio calculations in order to reduce their conformational space. We will show
      through first principles calculations on a monosubstituted bithiophene molecule
      how a full-length alkyl fragment can influence both side chain energetics and
      backbone flexibility in alkylthiophene-based polymers and copolymers. Folded side
      chains, characterized by a gauche arrangement of the second torsion angle from
      the ring, are found to be substantially favoured over extended ones, thanks to a
      network of CH-pi hydrogen-bond-like interactions with both aromatic rings. Trans
      planar (conjugated) arrangements of limit-ordered crystalline models, and cisoid
      sequences suitable for the investigation of chain-folding phenomena, are also
      discussed in detail. 

PMID- 24445691
TI  - Band alignment and optical absorption in  Ga(Sb)N alloys.
AB  - We extend the theory of band alignment proposed by Harrison to ternary and
      quaternary heteropolar semiconductors. Combining this with first-principles
      density functional theory incorporating the LDA/GGA+U formalism (LDA: local
      density approximation; GGA: generalized gradient approximation) can result in
      useful electronic structure predictions for new alloys. The practicality of this
      is demonstrated by application to the Ga(Sbx)N1-x alloys, where the feasibility
      of water splitting reaction under visible light irradiation is discussed.

PMID- 24445692
TI  - Marine microbiology: message in a bottle.

PMID- 24445693
TI  - Techniques & Applications: bacterial WGS made easy.

PMID- 24445694
TI  - E3 ubiquitin ligases and human papillomavirus-induced carcinogenesis.
AB  - Human papillomavirus (HPV) infection is clinically very common. It is usually a
      major risk factor in the development of cutaneous benign lesions, cervical cancer
      and a variety of other malignancies. The biological function of ubiquitination as
      an intracellular proteasomal-mediated form of protein degradation and an
      important modulator in the regulation of many fundamental cellular processes has
      been increasingly recognized over the last decade. HPV proteins have been
      demonstrated to evolve different strategies to utilize the ubiquitin system for
      their own purposes. The putative roles of E3 ubiquitin ligases in HPV-induced
      carcinogenesis have become increasingly apparent, although the mechanisms remain
      unclear. In this review we provide an update on the mechanisms of the involvement
      of E3 ubiquitin ligases in HPV-induced carcinogenesis, focusing on their
      interaction with HPV proteins and their roles in several signalling pathways.
      Targeting the E3 ubiquitin ligases might offer potential therapeutic strategies
      for HPV-related diseases in future. 

PMID- 24445695
TI  - Noninvasive Keratograph assessment of tear film break-up time and location in
      patients with age-related cataracts and dry eye syndrome.
AB  - OBJECTIVE: To investigate tear-film break-up time and spatial distribution via
      noninvasive Keratograph 4 in patients with cataracts and dry eye syndrome (DES).
      METHODS: Noninvasive first break-up time (NIKf-BUT) and average break-up time
      (NIKav-BUT) were evaluated via Keratograph 4 in patients with age-related
      cataracts and DES. The location and size of tear break regions were recorded and
      the distribution of first break-up areas was summarized. Patients also underwent
      conventional break-up time assessments (TBUT test and Schirmer's test). RESULTS:
      A total of 43 left and 43 right eyes were examined. There was no significant
      difference between TBUT and NIKav-BUT. NIKf-BUT was significantly shorter than
      TBUT. Both NIKf-BUT and NIKav-BUT correlated positively with TBUT. In both the
      left and right eye, the most common first break-up areas were the peripheral
      domain of the inferior precorneal surface and the central domain of the superior
      portion. CONCLUSIONS: The Keratograph 4 appears to provide an effective
      noninvasive method for assessing tear film, enabling effective preoperative
      evaluation of tear film break-up regularity, informing the location of the
      incision and reducing the probability of postoperative DES.

PMID- 24445696
TI  - Clinical and laboratory parameters associated with metabolic syndrome in Turkish
      patients with psoriasis.
AB  - OBJECTIVES: To assess clinical and laboratory parameters associated with
      metabolic syndrome in Turkish patients with moderate or severe plaque-type
      psoriasis and nonpsoriatic controls. METHODS: Patients with moderate or severe
      plaque psoriasis (patient group) or with nonpsoriatic dermatological disease
      (controls) were included. Waist circumference, weight, height and arterial blood
      pressure were measured, together with fasting blood glucose, triglyceride, high
      density lipoprotein (HDL), fibrinogen, homocysteine and adiponectin levels.
      Metabolic syndrome was diagnosed using National Cholesterol Education Program
      Adult Treatment Panel III criteria. RESULTS: Out of 90 patients (50 with
      psoriasis; 40 controls), metabolic syndrome was more frequent in the patient
      group than in controls. In terms of metabolic syndrome parameters, only
      hypertension was more frequent in patients with psoriasis compared with controls.
      There was no statistically significant difference between the patient and control
      groups for obesity, hypertriglyceridaemia, HDL levels or hyperglycaemia.
      Fibrinogen levels were increased and adiponectin levels were decreased in the
      psoriasis group. No between-group difference in homocysteine levels was found.
      CONCLUSION: In this small study, metabolic syndrome was found to be more
      frequently identified in Turkish patients with psoriasis than in controls;
      metabolic syndrome could lead to increased cardiovascular disease risk in
      patients with moderate to severe psoriasis.

PMID- 24445697
TI  - Cardiac structural and functional changes in old elderly patients with
      obstructive sleep apnoea-hypopnoea syndrome.
AB  - OBJECTIVE: To investigate cardiac structural changes in elderly patients with
      obstructive sleep apnoea-hypopnoea syndrome (OSAHS) and the impact on left
      ventricular systolic and diastolic function. METHODS: The study enrolled elderly
      patients with OSAHS and age-matched healthy control subjects. Cardiac structure,
      left ventricular diastolic function and left ventricular systolic function were
      measured using a Doppler ultrasound scanner and compared between the two groups.
      RESULTS: The study included 136 patients with OSAHS and 50 healthy control
      subjects. There were significant differences in the echocardiography indicators
      that reflect cardiac structure, including interventricular septum, left ventricle
      posterior wall thickness, and left ventricular mass and mass index between the
      two groups. There were significant differences between the two groups in the
      ventricular septal early diastolic myocardial peak velocity/late diastolic
      myocardial peak velocity (Em/Am), mitral annulus Em/Am, and left ventricle
      posterior wall Em/Am. There were also significant differences in the indicators
      of interventricular septum, mitral annulus and left ventricular posterior wall
      systolic peak velocity between the two groups. CONCLUSION: Elderly patients with
      OSAHS demonstrated cardiac structural changes and their left ventricular
      diastolic and systolic functions were significantly diminished.

PMID- 24445698
TI  - Asymmetric Mannich reaction between (S)-N-(tert-butanesulfinyl)-3,3,3
      trifluoroacetaldimine and malonic acid derivatives. Stereodivergent synthesis of
      (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids.
AB  - Inorganic as well as organic base catalysis was found to be effective for
      diastereoselective Mannich additions of malonic acid derivatives to (SS)-N-(tert
      butanesulfinyl)-3,3,3-trifluoroacetaldimine. In the presence of catalytic amounts
      of inorganic bases, n-BuLi or DMAP, the reaction gives the corresponding (R,SS)
      beta-aminomalonates in good yield and with diastereoselectivity up to 9/1 dr. In
      contrast, phosphazene bases favour the formation of the (S,SS)-diastereomer with
      selectivities as high as 99/1. Simple choosing of an appropriate base catalyst
      for the Mannich addition reaction allowed us to obtain enantiomerically pure (R)-
      or (S)-configured 3-amino-4,4,4-trifluorobutanoic acids after hydrolysis and
      decarboxylation of the corresponding beta-aminomalonates. 

PMID- 24445701
TI  - Personalized estimates of benefit from preventive care guidelines.

PMID- 24445702
TI  - Personalized estimates of benefit from preventive care guidelines.

PMID- 24445703
TI  - Absolute systolic ankle blood pressure versus ankle-brachial index.

PMID- 24445704
TI  - Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease.

PMID- 24445707
TI  - Web Exclusives. The Consult Guys - atrial fibrillation: how controlled is well
      controlled?

PMID- 24445708
TI  - ACP Journal Club. Review: sodium-glucose cotransporter 2 inhibitors reduce HbA1c
      and weight but increase infections.

PMID- 24445709
TI  - ACP Journal Club. Methylprednisolone injections reduced carpal tunnel syndrome
      symptoms at 10 weeks and surgery at 1 year.

PMID- 24445711
TI  - ACP Journal Club. In 85-year-old adults, MMSE predicted 5-year risk for first
      stroke better than Framingham score.

PMID- 24445710
TI  - ACP Journal Club. Fluconazole use during the first trimester of pregnancy was not
      associated with most major birth defects.

PMID- 24445712
TI  - ACP Journal Club. Annual or biennial FOBT screening reduced colorectal cancer
      mortality, but not all-cause mortality, at 30 years.

PMID- 24445713
TI  - ACP Journal Club. Review: new oral factor Xa inhibitors reduce DVT compared with
      standard thromboprophylaxis after THR or TKR.

PMID- 24445714
TI  - ACP Journal Club. Edoxaban was noninferior to warfarin for preventing recurrent
      venous thromboembolism, with less bleeding.

PMID- 24445715
TI  - ACP Journal Club. Review: dual-antiplatelet therapy does not reduce recurrent
      stroke but can increase ICH.

PMID- 24445716
TI  - ACP Journal Club. Review: antiplatelet therapies are more effective in smokers
      than nonsmokers.

PMID- 24445717
TI  - ACP Journal Club. Review: bariatric surgery increases weight loss and diabetes
      remission more than nonsurgical treatment.

PMID- 24445718
TI  - ACP Journal Club. Review: in type 2 diabetes, dipeptidyl peptidase-4 inhibitors
      do not increase pancreatitis.

PMID- 24445719
TI  - ACP Journal Club. In at-risk patients with type 2 diabetes, saxagliptin and
      placebo did not differ for CV events.

PMID- 24445720
TI  - Anterior and posterior corneal changes after crosslinking for keratoconus.
AB  - PURPOSE: To evaluate anterior and posterior changes in corneal topography and
      tomography after corneal crosslinking (CXL) in eyes with progressive keratoconus.
      METHODS: Scheimpflug analyses (Pentacam, Oculus) of 20 eyes with keratoconus
      performed before and after corneal CXL were included into retrospective analysis.
      Mean follow-up was 2 years. Changes in topographic, tomographic, and pachymetric
      values were statistically analyzed applying analysis of variance. Further, the
      distance and direction between the anterior maximum keratometry (K(max)) and the
      apex as well as the distance and direction between the thinnest point in corneal
      thickness (TPCT) and the corneal apex before and after CXL were studied. RESULTS:
      Two years after CXL, a statistically significant reduction of the keratometry at
      the flat meridian (-0.8 D, p < 0.05), the steep meridian (-0.5 D, p < 0.05), the
      "index of surface variance" (-5.3, p < 0.05), and the "index of highest
      decentration" (-0.05, p < 0.05) could be demonstrated. While the elevation of the
      front surface at the apex decreased (-1.5 MUm, p < 0.05), the back elevation at
      the apex (+2 MUm, p < 0.05) increased. Although not reaching statistical
      significance, the maximum front and back elevation demonstrated the same trend;
      while maximum front elevation data remained stable (-0.3 MUm, p = 0.961), maximum
      back elevation data increased (+6.7 MUm, p = 0.122). The corneal thickness at the
      apex (-22.0 MUm, p < 0.001) and the TPCT (-20.0 MUm, p < 0.001) decreased,
      leading to an increase of the corneal thickness progression from the corneal apex
      to the periphery. The position of K(max) and TPCT remained stable. CONCLUSIONS:
      Corneal topography proved to be useful in the follow-up for CXL because of
      significant changes in the keratometry. Increasing posterior elevation values,
      despite a stabilized anterior corneal surface, might be a sign of ongoing ectatic
      changes in the posterior corneal surface.

PMID- 24445721
TI  - Atropine slows myopia progression more in Asian than white children by meta
      analysis.
AB  - PURPOSE: To conduct a meta-analysis on the effects of atropine in slowing myopia
      progression and to compare Asian and white children and randomized controlled
      trials (RCTs) and observational studies. METHODS: Randomized controlled trials
      and observational studies that assessed the effects of all concentrations of
      atropine in slowing myopia progression in children were searched from MEDLINE,
      EMBASE, and the Cochrane Library up to April 2013. Jadad scoring was used to
      evaluate the quality of RCTs, and the Newcastle-Ottawa Scale was used for
      observational studies. RESULTS: Four RCTs and seven cohort studies (a kind of
      observational study) with 1815 children aged 5 to 15 years were included. The
      children had a baseline refraction of -0.50 to -9.75 diopters (D) and were
      followed up for 22.0 months (range, 12.0 to 36.5 months). The weighted mean
      differences in myopia progression in RCTs and cohort studies of Asian children
      were 0.55 D per year (p < 0.01) and 0.54 D per year (p < 0.001), respectively,
      and 0.35 D per year (p = 0.01) in cohort studies of white children. Compared with
      placebo, the risk of fast myopia progression (>1.0 D per year) using atropine was
      significantly decreased in both RCTs (odds ratio [OR], 0.14; p < 0.01) and cohort
      studies (OR, 0.08; p < 0.01), and the benefit of slow myopia progression (<0.50 D
      per year) using atropine was significantly increased in both RCTs (OR, 6.73; p <
      0.01) and cohort studies (OR, 22.10; p < 0.01). CONCLUSIONS: Atropine could
      significantly slow myopia progression in children, with greater effects in Asian
      than in white children. Randomized controlled trials and cohort studies provided
      comparable effects.

PMID- 24445722
TI  - Age, behavior, environment, and health factors in the soft contact lens risk
      survey.
AB  - PURPOSE: Previous studies have reported that the risk of corneal infectious and
      inflammatory events (CIEs) with soft contact lens (SCL) wear is highest in late
      adolescence and early adulthood. This study assesses the associations between
      patient age and other factors that may contribute to CIEs in young SCL wearers.
      METHODS: After ethics approvals and informed consent, a nonclinical population of
      young SCL wearers was surveyed in five US cities. Data from 542 SCL wearers aged
      12-33 years were collected electronically. Responses were analyzed by age bins
      (12-14, 15-17, 18-21, 22-25, 26-29, and 30-33 years) using chi-square test.
      RESULTS: The cohort was 34% male and balanced across age bins. There were several
      significant associations between survey response and age (in bins). Wearers aged
      18-21 years reported more recent nights with less than 6 hours of sleep (p <
      0.001), more colds/flu (p = 0.049), and higher stress levels (p < 0.001). Wearers
      18-21 and those 22-25 years were more likely to wear SCLs when showering (p <
      0.001) and also reported more frequent naps with SCLs (p < 0.001). They reported
      sleeping in SCLs after alcohol use (p = 0.031), when traveling (p = 0.001), and
      when away from home (p = 0.024). Lower rates of regular hand washing before lens
      application (p = 0.054) was also associated with these groups. In addition, the
      relationship between reactive replacement and recommended replacement was
      dependent on age (p < 0.0001). CONCLUSIONS: Patient age influences lens wearing
      behaviors, environmental exposures, and other determinants of health that may
      contribute to increased CIEs in younger wearers. Targeted, age-specific education
      should be considered for both new and established SCL wearers.

PMID- 24445724
TI  - High gas storage capacities and stepwise adsorption in a UiO type metal-organic
      framework incorporating Lewis basic bipyridyl sites.
AB  - A UiO type MOF with Lewis basic bipyridyl sites was synthesized and structurally
      characterized. After being activated by Soxhlet-extraction, this MOF exhibits
      high storage capacities for H2, CH4 and CO2, and shows unusual stepwise
      adsorption for liquid CO2 and solvents, indicating a sequential filling mechanism
      on different adsorption sites. 

PMID- 24445723
TI  - Effects of combining azilsartan medoxomil with amlodipine in patients with stage
      2 hypertension.
AB  - OBJECTIVE: The aim of the study was to measure the effects on blood pressure (BP)
      of the angiotensin receptor blocker azilsartan medoxomil, in 40 and 80 mg doses,
      combined with 5 mg of the calcium channel blocker amlodipine and to compare these
      effects with placebo plus amlodipine 5 mg. METHODS: This was a randomized,
      controlled, double-blind study of 6 weeks' duration in 566 patients with stage 2
      hypertension. The primary endpoint was 24-h systolic BP by ambulatory monitoring.
      RESULTS: The mean age of the participants was 58 years; men and women were
      equally represented, and baseline 24-h BP (153-154/93 mmHg) and clinic BP (165
      166/94-95 mmHg) were similar across the three treatment groups. After 6 weeks, 24
      h BP decreased by 25/15 mmHg in both the azilsartan medoxomil/amlodipine 40/5 and
      80/5 mg groups. These reductions were each greater than the 14/8 mmHg decrease
      with placebo plus amlodipine 5 mg (P<=0.001 for both comparisons). All treatments
      were well tolerated, and adverse events did not increase with the azilsartan
      medoxomil doses. Edema or fluid retention was less common in both combination
      groups (2.6 and 2.7%) than with placebo plus amlodipine (7.6%). CONCLUSION:
      Coadministration of azilsartan medoxomil with amlodipine was well tolerated and
      led to meaningful additional BP reductions compared with placebo plus amlodipine.

PMID- 24445725
TI  - Reversible severe hepatitis in anorexia nervosa: a case report and overview.
AB  - Mildly elevated transaminases are often observed in anorexia nervosa patients,
      but severe hepatitis is less common. We suggest that hypoperfusion is the
      pathogenetic factor that causes severe hepatitis in a patient with a very poor
      nutritional status and present an overview of previous case reports. In our
      patient, early initiation of intravenous fluids resulted in rapid recovery of the
      liver test abnormalities, despite minimal oral caloric intake, the refusal of
      enteral feeding and the development of a hypoglycemic coma. Two months after
      admission, transaminases had normalized. Reversible severe hepatitis has been
      described in most of the cases, with only one anorexia nervosa-related fatal
      hepatitis. In general, both adequate hydration and gradual enteral feeding with
      monitoring of electrolytes are essential in the management of anorexia patients
      with severe hepatitis. 

PMID- 24445726
TI  - PET-CT as a predictor of outcome in resectable colorectal liver metastases.
AB  - INTRODUCTION: PET-computed tomography (PET-CT) is a useful staging imaging
      modality in colorectal liver metastases (CRLM). This study aimed to determine
      whether PET-CT parameters, standardized uptake value (SUV) and reconstructed
      tumour volume (RTV), are predictors of prognosis and survival. METHODS: A study
      of all resectable CRLM patients in the regional HPB unit from 2007-2009 was
      performed. Preoperative PET-CT scans were retrospectively reviewed; SUV, diameter
      and RTV for each lesion was recorded. Correlation analysis was performed with
      other pathological and biochemical parameters, by Pearson's correlation analysis.
      Survival analysis was performed using Cox regression hazard model. A P value of
      less than 0.05 was considered statistically significant. RESULTS: A total of 79
      patients were included. SUV moderately correlated with tumour diameter, both PET
      CT (r=0.4927; P<0.0001) and histology (r=0.4513; P=0.0003); RTV (r=0.4489;
      P<0.001), preoperative carcinoembryonic antigen (CEA) (r=0.4977; P=0.0001), and
      postoperative CEA (r=0.3727; P=0.004). Multivariate analysis found that an
      independent predictor of SUVmax was preoperative CEA (P=0.03). RTV strongly
      correlated with preoperative CEA (r=0.9389; P<0.0001). SUV and RTV had a negative
      effect on survival. CONCLUSION: PET-CT, in the setting of CRLM, may have a
      prognostic role in assessing survival. Although no definite conclusions can be
      drawn regarding the prognostic role of SUV and RTV, it acts to reinforce the need
      for further prospective studies to validate these findings.

PMID- 24445727
TI  - Mucosal healing in pediatric Crohn's disease after anti-TNF therapy: a long-term
      experience at a single center.
AB  - PURPOSE: The anti-tumor necrosis factor (TNF) agents infliximab (IFX) and
      adalimumab (ADA) have been recently introduced to treat severe inflammatory bowel
      disease (IBD) that is unresponsive to other drugs. Several studies have confirmed
      the safety and efficacy of these agents for adult IBD patients, whereas there is
      less data on pediatric IBD. Mucosal healing, associated with fewer complications
      and surgeries, is considered the goal of treatment by some authors. The objective
      of this study was to evaluate the safety and efficacy (in terms of endoscopic,
      clinical, and laboratoristic response) of IFX and ADA in a cohort of pediatric
      patients with Crohn's disease (CD). METHODS: We conducted a retrospective
      analysis of prospectively collected data; we studied 33 patients (20 male, 13
      female) with a diagnosis of CD established before 18 years of age: 29/33 were
      treated with IFX and 19/33 received ADA (four of them were naive to IFX). We
      evaluated clinical, endoscopic, and laboratoristic response to IFX and ADA for
      each patient and recorded the adverse effects of these drugs. RESULTS: With
      regard to IFX treatment, 22.2% of patients achieved mucosal healing and 44.4%
      showed an endoscopic response. With regard to ADA therapy, 25% of patients
      achieved mucosal healing and 50% showed an endoscopic response. Overall clinical
      response rates for IFX and ADA were 84 and 92.3%, respectively. Both drugs were
      well tolerated. CONCLUSION: To our knowledge, this is the first study reporting
      mucosal healing after ADA therapy in pediatric CD. We found significant mucosal
      healing and response rates in our group of patients. Compared with other
      pediatric studies, we reported similar clinical response rates and longer follow
      up of patients.

PMID- 24445728
TI  - Genetic polymorphisms of proangiogenic factors seem to favor hepatocellular
      carcinoma development in alcoholic cirrhosis.
AB  - OBJECTIVE: Angiogenesis has been associated with hepatic cirrhosis and
      hepatocellular carcinoma (HCC). Alcohol promotes liver hypoxia, a trigger of
      angiogenesis. We aimed to evaluate whether the frequency of three polymorphisms
      in hypoxia-induced factor-1alpha (HIF-1alpha), vascular endothelial growth factor
      A (VEGFA), and KDR (encoding vascular endothelial growth factor receptor 2) genes
      was higher in alcoholics presenting liver disease (ALD) and ALD patients who
      developed HCC. MATERIALS AND METHODS: Functional HIF-1alpha 1744C/T, VEGFA
      2578C/A, and KDR 1416A/T single-nucleotide polymorphisms were studied in 125 ALD
      patients and 88 heavy drinkers without liver disease (NLD). ALD patients were
      followed up to 9 years or until they died; 26 patients developed HCC. RESULTS:
      ALD patients were older than NLD (56+/-11 vs. 50+/-13, P<0.001), but drank less
      (215+/-164 vs. 331+/-293 g/day, P<0.001). No differences were found between HIF
      1alpha, VEGFA, or KDR allelic frequencies or genotypes, isolated or
      simultaneously, between ALD and NLD. In ALD patients, those who developed HCC had
      a higher KDR 1416T allele frequency (36 vs. 15%, P=0.004; odds ratio 2.72; 95%
      confidence interval 1.35-5.46). There was also a progressive increase in
      genotypes with one or two T alleles in patients who developed HCC: AA 50 vs. 73%,
      AT 35 vs. 23%, and TT 15 vs. 4% (P=0.009). The simultaneous presence of KDR 1416T
      and VEGFA 2578A was associated with an increased risk of HCC (odds ratio 3.088;
      95% confidence interval 1.20-7.96). CONCLUSION: Genetic polymorphisms in
      proangiogenic factors did not associate with the risk of ALD in heavy drinkers.
      However, KDR and VEFGA polymorphisms may confer an increased risk of HCC in
      patients with ALD.

PMID- 24445729
TI  - Mast cells in irritable bowel syndrome and ulcerative colitis: function not
      numbers is what makes all the difference.

PMID- 24445730
TI  - Predicting short-term mortality and long-term survival for hospitalized US
      patients with alcoholic hepatitis.
AB  - BACKGROUND: No study has evaluated current scoring systems for their accuracy in
      predicting short and long-term outcome of alcoholic hepatitis in a US population.
      METHODS: We reviewed electronic records for patients with alcoholic liver disease
      (ALD) admitted to Parkland Memorial Hospital between January 2002 and August
      2005. Data and outcomes for 148 of 1,761 admissions meeting pre-defined criteria
      were collected. The discriminant function (DF) was revised (INRdf) to account for
      changes in prothrombin time reagents that could potentially affect identification
      of risk using the previous DF threshold of >32. Admission and theoretical peak
      scores were calculated by use of the Model for End-stage Liver Disease (MELD).
      Analysis models compared five different scoring systems. RESULTS: INRdf was
      closely correlated with the old DF (r (2) = 0.95). Multivariate analysis of the
      data showed that survival for 28 days was significantly associated with a scoring
      system using a combination of age, bilirubin, coagulation status, and creatinine
      (p < 0.001), and an elevated ammonia result within two days of admission (p =
      0.012). When peak values for MELD were included, they were the most significant
      predictor of short-term mortality (p < 0.001), followed by INRdf (p = 0.006).
      CONCLUSION: On admission, two scoring systems that identify a subset of patients
      with severe alcoholic liver disease are able to predict >50 % mortality at four
      weeks and >80 % mortality at six months without specific treatment.

PMID- 24445731
TI  - Celiac disease is diagnosed less frequently in young adult males.
AB  - BACKGROUND: The female predominance in celiac disease is difficult to explain
      because population-based screening studies reveal similar rates for celiac
      disease-specific autoantibodies in males and females. AIM: The aim of this study
      was to explore the role of age and gender in the presentation of celiac disease.
      METHODS: The frequency of presentation according to age, gender and mode of
      presentation was determined by analysis of a prospectively maintained database of
      children and adults seen at a tertiary medical center. RESULTS: Of 1,682 patients
      (68 % female) aged 3 months to 86 years who were diagnosed with celiac disease,
      age at diagnosis in females peaked at 40-45 years, whereas the age at diagnosis
      for males had two peaks: 10-15 and 35-40 years. A significantly lower percentage
      of males in early adulthood were diagnosed compared with males in all other age
      groups (P < 0.0001). The young and elderly had a more even gender distribution.
      CONCLUSIONS: Based on our analysis, males are diagnosed with celiac disease less
      frequently than females, especially in early adulthood. There should be more
      emphasis on the diagnosis of celiac disease among young adult males.

PMID- 24445732
TI  - Compliance and persistence to oral bisphosphonate therapy following initiation
      within a secondary fracture prevention program: a randomised controlled trial of
      specialist vs. non-specialist management.
AB  - Following initiation of oral bisphosphonate therapy through a secondary fracture
      prevention program, 2-year treatment compliance and persistence remained high and
      were similar in patients randomised to follow-up by either the program or primary
      care physician. Thus, community-based and specialist management are equally
      effective in supporting compliance and persistence with anti-osteoporotic
      treatments. INTRODUCTION: The purpose of this study was to determine whether
      management by a secondary fracture prevention (SFP) program (aka "fracture
      liaison service") results in better compliance and persistence to oral
      bisphosphonate therapy than follow-up by the primary care physician, after
      initiation within an SFP program. METHODS: This prospective RCT included 102
      patients with incident osteoporotic fractures referred to a SFP program in
      Sydney, Australia. Following oral bisphosphonate therapy initiation, patients
      were randomised to either 6-monthly follow-up with the SFP program (group A) or
      referral to their primary care physician with a single SFP program visit at 24
      months (group B). Compliance and persistence to treatment were measured using
      pharmaceutical claims data. Predictors of compliance and persistence and
      associations between compliance and persistence, and changes in bone mineral
      density (BMD) or bone resorption marker, urinary deoxypyridinoline over 24 months
      were analysed. RESULTS: The median medication possession ratio at 24 months was
      0.78 (IQR, 0.50-0.93) in group A and 0.79 (IQR, 0.48-0.96) in group B (p = 0.68).
      Persistence at 24 months was also similar in both groups (64 vs. 61%,
      respectively; p = 0.75). After adjusting for confounders, patients in group A
      were not more likely to be compliant (OR, 1.06; 95% CI, 0.46-2.47) or persistent
      (HR, 0.83; 95% CI, 0.27-1.67) than those randomised to group B. Time-based
      changes in BMD or bone turnover were not associated with compliance or
      persistence. CONCLUSION: Compliance and persistence to oral bisphosphonate
      therapy remain high amongst patients initiated within an SFP program, with
      community-based and SFP program management being equally effective in maintaining
      therapeutic compliance and persistence over 2 years. These results indicate that
      one of the main functions of an SFP program may be the initiation of therapy
      rather than continuous patient monitoring.

PMID- 24445733
TI  - Narrow band imaging-guided endoscopic biopsy for intraventricular and
      paraventricular brain tumors: clinical experience with 14 cases.
AB  - BACKGROUND: Narrow-band imaging (NBI) has been confirmed as a useful endoscopic
      technique to distinguish neoplasm from normal tissue, on the basis of the
      enhanced neovascularity of tumor tissue. NBI-guided tissue biopsy for
      laryngopharyngeal and digestive lesions is a novel methodology, but the
      feasibility for central nervous system tumors remains unclear. The aim of our
      study was to evaluate the feasibility of NBI-guided biopsy for intraventricular
      and paraventricular tumor. METHODS: Fourteen patients with intraventricular or
      paraventricular tumors underwent neuroendoscopic biopsy using a videoscope with
      NBI. Ventricular walls and tumors were observed using conventional imaging,
      followed by NBI. Colors of ventricle walls and tumors visualized using NBI were
      compared to those visualized under conventional imaging. Extracted specimens were
      stained using CD31 antibody and numbers of microvessels in each specimen were
      counted for analyzing vascular density. RESULTS: Normal ventricle walls were a
      similar color under conventional imaging and NBI. Tumor surfaces appeared to be
      cyan in color under NBI. Vessels on the tumor were more clearly visualized with
      NBI than with conventional imaging. NBI was able to identify tumor surfaces that
      were not perceptible on conventional imaging. All specimens in the lesion
      surfaces from cyan-colored areas under NBI contained tumor cells. Specimens
      extracted from regions that appeared cyan in color under NBI (51.0 vessels/mm(2))
      had significantly greater vascular density than regions that appeared a normal
      color (17.4 vessels/mm(2); p = 0.039). CONCLUSION: NBI-guided biopsy of
      intraventricular and paraventricular tumors is feasible for visualizing tumor
      surface-enhancing neovascularities. NBI would contribute to accurate histological
      diagnosis while minimizing injury to surrounding structures.

PMID- 24445734
TI  - Utility of 320-detector row CT for diagnosis and therapeutic strategy for
      paraclinoid and intracavernous aneurysms.
AB  - BACKGROUND: The aim of this study was (1) to assess the diagnostic accuracy of
      320-detector row computed tomography (CT) for paraclinoid and intracavernous
      aneurysms, and (2) to investigate whether this method provides sufficient
      information for surgery. METHODS: A total of 14 patients with 16 unruptured
      proximal ICA aneurysms underwent three-dimensional CT angiography (3D-CTA) fusion
      imaging, which was created by superimposing 3D-CT venography data and/or 3D-bone
      data onto 3D-CTA data using 320-detector row CT, magnetic resonance imaging
      (MRI), and 3D digital subtraction angiography (DSA). The images of each modality
      were assessed using intraoperative findings as the reference standard. RESULTS:
      All aneurysms were clearly visualized on 320-detector row CT. Bone subtraction
      and arterio-venous discrimination were accurate. On 3D-CTA fusion images, 11
      aneurysms were diagnosed as "extracavernous" and five as "intracavernous". No
      discordance in aneurysm location between the 3D-CTA fusion images and the
      intraoperative findings was found. In contrast, discordance between MRI and
      intraoperative findings were found in five of the 16 cases (31%), which was
      significantly more frequent than with 3D-CTA (p = 0.043). The findings DSA, which
      was performed in nine patients, were also in excellent agreement with the
      intraoperative findings. However, 3D-CTA fusion imaging provided more
      comprehensive information, including venous and osseous structures, than 3D-DSA.
      The 320-detector row CTA after surgery demonstrated a clear relationship between
      the clip and aneurysmal neck with notably few artifacts, which suggested the
      utility of this modality for postoperative assessment. CONCLUSIONS: The 320
      detector row CT provided high accuracy for the diagnosis of paraclinoid and
      intracavernous aneurysms. This technique also provided comprehensive depiction of
      the aneurysms and surrounding structures. Therefore, this modality might be
      useful for the diagnosis of the paraclinoid and intracavernous aneurysms and for
      developing a surgical treatment plan.

PMID- 24445735
TI  - [Locoregional breast radiotherapy and concurrent treatment with trastuzumab].
AB  - The overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2) is
      observed in 15% of breast cancers and associated with poor prognosis in terms of
      overall survival. Trastuzumab is an anti-HER2 targeted therapy, leading to a
      specific inhibition of the molecular mechanisms triggered by this receptor. In an
      adjuvant setting, trastuzumab and radiotherapy have each proved their oncologic
      efficacy in the management of the breast tumours presenting this molecular
      profile. However, both treatments expose to an increased risk of toxicities,
      particularly cardiovascular ones. Moreover, the radiosensitizing effect of
      trastuzumab has been proved in vitro and in vivo. Hence, in clinical practice,
      the benefit/risk ratio of a concurrent treatment remains to be defined. This
      literature review has for purposes to describe the rationale making conceivable
      the administration of trastuzumab concurrently with locoregional breast
      radiotherapy, and to remind the results of the clinical studies having assessed
      this therapeutic association.

PMID- 24445736
TI  - Genotyping with CRISPR-Cas-derived RNA-guided endonucleases.
AB  - Restriction fragment length polymorphism (RFLP) analysis is one of the oldest,
      most convenient and least expensive methods of genotyping, but is limited by the
      availability of restriction endonuclease sites. Here we present a novel method of
      employing CRISPR/Cas-derived RNA-guided engineered nucleases (RGENs) in RFLP
      analysis. We prepare RGENs by complexing recombinant Cas9 protein derived from
      Streptococcus pyogenes with in vitro transcribed guide RNAs that are
      complementary to the DNA sequences of interest. Then, we genotype recurrent
      mutations found in cancer and small insertions or deletions (indels) induced in
      cultured cells and animals by RGENs and other engineered nucleases such as
      transcription activator-like effector nucleases (TALENs). Unlike T7 endonuclease
      I or Surveyor assays that are widely used for genotyping engineered nuclease
      induced mutations, RGEN-mediated RFLP analysis can detect homozygous mutant
      clones that contain identical biallelic indel sequences and is not limited by
      sequence polymorphisms near the nuclease target sites. 

PMID- 24445738
TI  - Nine private hospitals should be sold to increase competition, says commission.

PMID- 24445737
TI  - UVA irradiation of human skin vasodilates arterial vasculature and lowers blood
      pressure independently of nitric oxide synthase.
AB  - The incidence of hypertension and cardiovascular disease (CVD) correlates with
      latitude and rises in winter. The molecular basis for this remains obscure. As
      nitric oxide (NO) metabolites are abundant in human skin, we hypothesized that
      exposure to UVA may mobilize NO bioactivity into the circulation to exert
      beneficial cardiovascular effects independently of vitamin D. In 24 healthy
      volunteers, irradiation of the skin with two standard erythemal doses of UVA
      lowered blood pressure (BP), with concomitant decreases in circulating nitrate
      and rises in nitrite concentrations. Unexpectedly, acute dietary intervention
      aimed at modulating systemic nitrate availability had no effect on UV-induced
      hemodynamic changes, indicating that cardiovascular effects were not mediated via
      direct utilization of circulating nitrate. UVA irradiation of the forearm caused
      increased blood flow independently of NO synthase (NOS) activity, suggesting
      involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy
      studies of human skin pre-labeled with the NO-imaging probe diaminofluorescein 2
      diacetate revealed that UVA-induced NO release occurs in a NOS-independent, dose
      dependent manner, with the majority of the light-sensitive NO pool in the upper
      epidermis. Collectively, our data provide mechanistic insights into an important
      function of the skin in modulating systemic NO bioavailability, which may account
      for the latitudinal and seasonal variations of BP and CVD. 

PMID- 24445739
TI  - Spectroscopy of the breaking bond: the diradical intermediate of the ring opening
      in oxazole.
AB  - Bond breaking is a challenging problem in both experimental and theoretical
      chemistry, due to the transient nature and multi-configurational electronic
      structure of dissociating molecules. We use anion photodetachment to probe the
      diradical interactions in the ring-opening reaction of oxazole and obtain a self
      consistent picture of the breaking bond. Starting from the closed-shell cyclic
      molecule, the reaction is launched on the anion potential, as an attached
      electron cleaves a carbon-oxygen bond. In the photodetachment, two neutral
      potential regions are sampled. One corresponds to a completely dissociated bond,
      while the other - to the bond fragments separated by approximately 3 A. At this
      chemically relevant distance, signatures of lingering through-space interactions
      between the radical centers are observed. 

PMID- 24445741
TI  - Chronic kidney disease: haemodialysis catheter care in practice.
AB  - A new haemodialysis catheter-care procedure has been reported, including exit
      site disinfection with chlorhexidine gluconate that results in a sustained
      reduction in bacteraemia rates, new intravenous antibiotic starts and sepsis
      associated and access-associated hospitalization rates compared with standard
      care. These findings have potential implications for the prevention of
      haemodialysis catheter-associated infections.

PMID- 24445742
TI  - Tubular disease: mistargeted protein disrupts mitochondrial metabolism in
      inherited Fanconi syndrome.

PMID- 24445743
TI  - Transplantation: Increased ESRD and mortality risk for kidney donors?
AB  - For most patients with end-stage renal disease (ESRD), a kidney transplant is the
      best treatment option. Compared with dialysis, a successful kidney transplant is
      associated with increased life expectancy and improved quality of life; a living
      donor transplant is associated with better long-term results than a deceased
      donor transplant.

PMID- 24445740
TI  - Biomarkers for kidney transplant rejection.
AB  - The immune management of organ transplant recipients is imperfect. Beyond general
      dosing guidelines for immunosuppressive agents and clinical diagnostic tests for
      rejection or infection, there are few objective tools to determine the aggregate
      status of a patient's alloimmune response or protective immune capacity. The lack
      of prognostic precision significantly contributes to patient morbidity and
      reduces long-term allograft survival after kidney transplantation. Noninvasive
      biomarkers that could serve as predictive tools or surrogate end points for
      rejection might help clinicians individualize immunosuppression and allow for
      early intervention, ideally prior to clinically evident organ dysfunction.
      Although the growing understanding of organ rejection has provided numerous
      candidate biomarkers, none has been confirmed in robust validation studies as
      sufficiently useful to guide clinical practice independent of traditional
      clinical methods. In this Review, the general characteristics of biomarkers and
      surrogate end points; current biomarkers under active clinical investigation; and
      the prominent barriers to the translation of biomarkers into clinical practice
      are discussed. 

PMID- 24445745
TI  - Hypertension: understanding baroreflex dysfunction in chronic kidney disease.

PMID- 24445746
TI  - Transplantation: immunoadsorption combined with membrane filtration might enhance
      desensitization.

PMID- 24445747
TI  - Molecular identification of first putative aquaporins in snails.
AB  - Aquaporins (AQPs), also known as water channel proteins, are members of a large
      protein family termed Major Intrinsic Proteins (MIP). The mammalian AQPs have
      been most comprehensively described, while knowledge about AQPs in invertebrates
      is limited mainly to insects. Not a single AQP protein has been described in
      snails to date. Consequently, we decided to search for the proteins in gastropod
      representatives, namely Lymnaea stagnalis, Catascopia occulta, and Stagnicola
      palustris (Mollusca; Gastropoda; Pulmonata; Lymnaeidae). Using the molecular
      approach, we identified L. stagnalis, C. occulta, and S. palustris open reading
      frames (ORFs) showing homology to AQP genes available in GenBank database, and
      characterized the encoded proteins, referred to as LsAQP1, CoAQP1, and SpAQP1,
      respectively. The putative snail aquaporins contain 299 amino acids, have a
      molecular mass of about 32 kDa, display the general AQP topology and three
      dimensional structure congruent with orthodox AQPs, i.e., water-specific ones.
      Due to high levels of similarity in their characteristics, LsAQP1 was chosen for
      further studies, as the obtained results were supposed to be applicable for
      CoAQP1 and SpAQP1. Expression analysis revealed the presence of LsAQP1 transcript
      in the digestive tract, the cerebral ganglia, the kidney, the reproductive
      system, and the foot, suggesting that LsAQP1 as well as CoAQP1 and SpAQP1 are
      ubiquitous proteins and may play important roles in many essential water
      transport processes. The role appears to be confirmed by results of the yeast
      growth complementation assay pointing at functionality of LsAQP1. Thus, the
      obtained results support the AQP expression in gastropod tissues for the first
      time. 

PMID- 24445744
TI  - Acute kidney injury-epidemiology, outcomes and economics.
AB  - Acute kidney injury (AKI) is a widespread problem of epidemic status. Compelling
      evidence indicates that the incidence of AKI is rapidly increasing, particularly
      among hospitalized patients with acute illness and those undergoing major
      surgery. This increase might be partially attributable to greater recognition of
      AKI, improved ascertainment in administrative data and greater sensitivity of
      consensus diagnostic and classification schemes. Other causes could be an ageing
      population, increasing incidences of cardiovascular disease, diabetes mellitus
      and chronic kidney disease (CKD), and an expanding characterization of modifiable
      risk factors, such as sepsis, administration of contrast media and exposure to
      nephrotoxins. The sequelae of AKI are severe and characterized by increased risk
      of short-term and long-term mortality, incident CKD and accelerated progression
      to end-stage renal disease. AKI-associated mortality is decreasing, but remains
      unacceptably high. Moreover, the absolute number of patients dying as a result of
      AKI is increasing as the incidence of the disorder increases, and few proven
      effective preventative or therapeutic interventions exist. Survivors of AKI,
      particularly those who remain on renal replacement therapy, often have reduced
      quality of life and consume substantially greater health-care resources than the
      general population as a result of longer hospitalizations, unplanned intensive
      care unit admissions and rehospitalizations. 

PMID- 24445748
TI  - An efficient wavelet based approximation method to steady state reaction
      diffusion model arising in mathematical chemistry.
AB  - The mathematical model of Rahamathunissa and Rajendran (J Math Chem 44:849-861,
      2008) in an amperometric biosensor response is discussed. In this paper, we have
      applied the shifted second kind Chebyshev wavelets (CW) to obtain the numerical
      solutions of reaction-diffusion equations containing a nonlinear term related to
      Michaelis-Menton kinetics of the enzymatic reaction. The application of the
      shifted second kind CW operational matrices for solving initial and boundary
      value problems is presented. The obtained numerical results demonstrate efficient
      and applicability of the proposed method. The power of the manageable method is
      confirmed. Moreover the use of shifted second kind CW method is found to be
      simple, efficient, accurate, small computation cost, and computationally
      attractive. 

PMID- 24445749
TI  - Combinatorial gene editing in mammalian cells using ssODNs and TALENs.
AB  - The regulation of gene editing is being elucidated in mammalian cells and its
      potential as well as its limitations are becoming evident. ssODNs carry out gene
      editing by annealing to their complimentary sequence at the target site and
      acting as primers for replication fork extension. To effect a genetic change, a
      large amount of ssODN molecules must be introduced into cells and as such induce
      a Reduced Proliferation Phenotype (RPP), a phenomenon in which corrected cells do
      not proliferate. To overcome this limitation, we have used TAL-Effector Nucleases
      (TALENs) to increase the frequency, while reducing the amount of ssODN required
      to direct gene correction. This strategy resolves the problem and averts the
      serious effects of RPP. The efficiency of gene editing can be increased
      significantly if cells are targeted while they progress through S phase. Our
      studies define new reaction parameters that will help guide experimental
      strategies of gene editing. 

PMID- 24445750
TI  - Lattice dynamics of the icosahedral quasicrystals i-ZnMgSc and i-ZnAgSc and the
      cubic 1/1-approximant Zn6Sc.
AB  - A comparison of periodic approximants and their quasicrystalline counterparts
      offers the opportunity to better understand the structure, physical properties
      and stabilizing mechanisms of these complex phases. We present a combined
      experimental and computational study of the lattice dynamics of the icosahedral
      quasicrystals i-ZnMgSc and i-ZnAgSc and compare these to the lattice dynamics of
      the cubic 1/1-approximant Zn6Sc. The two phases, quasicrystal and approximant,
      are built up from the same atomic clusters, which are packed either
      quasiperiodically or on a body centered cubic lattice, respectively. Using
      inelastic neutron scattering and atomic scale simulations, we show that the
      vibrational spectra of these three systems are very similar, however, they
      contain a clear signature of the increasing structural complexity from
      approximant to quasicrystal.

PMID- 24445752
TI  - Fetal heart rate during termination of maternal supraventricular tachycardia with
      adenosine.

PMID- 24445751
TI  - Valve-in-valve implantations: is this the new standard for degenerated
      bioprostheses? Review of the literature.
AB  - Transcatheter aortic valve implantation has established itself as an alternative
      treatment for patients with valvular disease. In the current context of
      increasing bioprosthetic valve implants and an ageing population with growing
      comorbidities, a less invasive approach to the treatment of bioprosthetic
      dysfunction would be an appealing alternative to the standard of care.
      Transcatheter valve-in-valve implantation could be an alternative for patients
      who are deemed to be a high surgical risk. The valve-in-valve procedure is a
      minimally invasive percutaneous procedure where a valve can be implanted directly
      within a failing bioprosthetic valve. This technique can be applied to
      dysfunctional aortic bioprosthetic valves and can also be used in the pulmonary
      and atrioventricular valve bioprosthesis. We review the current literature to
      assess whether this technique may be the new standard for degenerated
      bioposthesis. 

PMID- 24445753
TI  - Health-related quality of life in children and adolescents with celiac disease:
      patient-driven data from focus group interviews.
AB  - PURPOSE: Celiac disease (CD) is a chronic inflammatory disease requiring constant
      management with a gluten-free diet (GFD). Little is known about how CD impacts on
      health-related quality of life (HRQOL) in children and adolescents, and how they
      feel about and cope with CD and GFD. This qualitative study explores the impact
      of CD and GFD on HRQOL in everyday living of children and adolescents. METHODS:
      In focus group interviews, we investigated HRQOL in children and adolescents with
      CD in order to identify patient concerns in living with CD and on a GFD. Seven
      focus groups were formed with 23 children/adolescents and 3 parents. Interviews
      were transcribed verbatim. Grounded theory approach was applied to analyse the
      interviews. RESULTS: CD had varying impact on the children and adolescents HRQOL.
      Two major categories emerged with importance for HRQOL in children and
      adolescents with CD, having CD (constructed from the six subcategories: symptoms,
      the diagnosis-process, self-perception, awareness of CD, social and emotional
      impact of CD, and thoughts about the future) and coping with CD (constructed from
      the two subcategories: coping with food and coping with social situations). The
      complexity of coping with CD in social situations that involve food is presented
      in a flowchart. CONCLUSIONS: Children and adolescents showed large diversity in
      how much impact CD has on their HRQOL. Different ways of coping with CD and GFD
      were identified. Findings will be used to generate a patient-driven disease
      specific questionnaire to measure HRQOL in children and adolescents with CD.

PMID- 24445754
TI  - The formation mechanism and photocatalytic activity of hierarchical NiAl-LDH
      films on an Al substrate prepared under acidic conditions.
AB  - NiAl-LDH films with hierarchical morphology have been fabricated by immersion of
      an Al substrate in Ni(2+)-containing solutions under strong acidic conditions,
      and the growth processes of the films are discussed in this communication. The as
      prepared LDH films exhibit high activity in the photocatalytic degradation of
      organic contaminants. 

PMID- 24445755
TI  - A distinct variant of mixed dysarthria reflects parkinsonism and dystonia due to
      ephedrone abuse.
AB  - A distinctive alteration of speech has been reported in patients suffering from
      ephedrone-induced parkinsonism. However, an objective assessment of dysarthria
      has not been performed in ephedrone users. We studied 28 young Caucasian men from
      Georgia with a previous history of ephedrone abuse and compared them to 25 age
      matched healthy controls. Speech examination, brain MRI, and NNIPPS-Parkinson
      plus scale were performed in all patients. The accurate differential diagnosis of
      dysarthria subtypes was based on the quantitative acoustic analyses of 15 speech
      dimensions. We revealed a distinct variant of mixed dysarthria with a combination
      of hyperkinetic and hypokinetic components representing the altered motor
      programming of dystonia and bradykinesia in ephedrone-induced parkinsonism.
      According to acoustic analyses, all patients presented at least one affected
      speech dimension, whereas dysarthria was moderate in 43% and severe in 36% of
      patients. Further findings indicated relationships between motor subscores of
      dystonia and bradykinesia and speech components of loudness (r = -0.54, p <
      0.01), articulation (r = 0.40, p < 0.05), and timing (r = -0.53, p < 0.01). In
      ephedrone-induced parkinsonism a prominent mixed hyperkinetic-hypokinetic
      dysarthria occurs that appears related to marked dystonia and bradykinesia and
      probably reflects manganese induced toxic and neurodegenerative damage to the
      globus pallidus internus and substantia nigra.

PMID- 24445756
TI  - Local relapse after breast-conserving therapy for ductal carcinoma in situ: a
      European single-center experience and external validation of the Memorial Sloan
      Kettering Cancer Center DCIS nomogram.
AB  - PURPOSE: Adjuvant treatments after breast-conserving surgery (BCS) for ductal
      carcinoma in situ to prevent local relapse are considered standard of care.
      However, patient selection to prevent increased morbidity without proven survival
      benefit remains a challenge. To predict the risk of ipsilateral breast tumor
      relapse (IBTR) after BCS, the Memorial Sloan-Kettering Cancer Center (MSKCC)
      developed a nomogram. The aim of this study was to develop our own prediction
      model for IBTR and to provide an external validation of the MSKCC nomogram.
      METHODS: From 1973 to 2010, 467 patients were treated with BCS for ductal
      carcinoma in situ at the University Hospital Leuven. Clinicopathologic and
      treatment parameters of all patients were used to create a multivariable model.
      The predictive value of the model was evaluated using the concordance index (C
      index) and concordance probability estimate (CPE). Multiple imputation was used
      to account for missing data to allow the MSKCC model to be tested on 467
      patients. RESULTS: Median follow-up was 7.2 years, with 48 women who developed an
      IBTR. Omission of adjuvant endocrine therapy, younger age, and positive or close
      surgical margins were significantly associated with an increased risk of IBTR.
      The bootstrap-corrected C-index for 10-year prediction by our own model was 0.63
      and the CPE was 0.61. The C-index and CPE for the 10-year relapse probabilities
      predicted by the MSKCC nomogram were 0.66 and 0.61, respectively. CONCLUSIONS:
      Despite the small number of events, the need for multiple imputation, and few
      patients without radiation, the MSKCC nomogram performance was somewhat better
      than our model. This shows that the MSKCC nomogram is externally valid. The MSKCC
      nomogram allows users to integrate the information from 10 different variables to
      provide a more precise risk stratification than the use of conventional single
      variables or hazard ratios.

PMID- 24445757
TI  - A randomized, double-blind, 2-period, placebo-controlled crossover trial of a
      sustained-release methylphenidate in the treatment of fatigue in cancer patients.
AB  - PURPOSE: This study assessed the efficacy of methylphenidate versus placebo for
      cancer-related fatigue reduction. Other objectives were to analyze cytokine
      levels and to determine the effects of methylphenidate on other symptoms,
      cognitive function, work yield, and patients' perceptions and preferences.
      METHODS: Patients were randomly assigned (1:1) to receive methylphenidate-placebo
      or placebo-methylphenidate for 4 weeks. Patients crossed over after 2 weeks.
      Wilcoxon signed rank tests and McNemar tests were used to assess continuous and
      categorical variables. The primary efficacy endpoint was change in the level of
      worst fatigue on the Brief Fatigue Inventory (BFI) at the end of each 2-week
      period. RESULTS: The mean baseline BFI score was moderate (5.7). Methylphenidate
      treatment did not affect patients' worst level of fatigue or other symptoms.
      Results from the Wechsler Adult Intelligence Scale Digit Symbol Test and the
      Hopkins Verbal Learning Test with BFI interference questions and BFI activity
      questions showed significant improvement in the methylphenidate-treated patients'
      verbal learning, memory, visual perception, analysis, and scanning speed.
      Patients treated with methylphenidate missed significantly fewer work hours owing
      to health reasons and worked significantly more hours. After 4 weeks, 64% of
      patients reported that methylphenidate improved their cancer-related fatigue, and
      58% wanted to continue treatment. Significant difference in interleukin 6R
      (positive), interleukin 10 (negative), and tumor necrosis factor alpha (positive)
      was noted between the methylphenidate and the placebo group. CONCLUSIONS: Low
      dose methylphenidate did not improve cancer-related fatigue. Patients taking
      methylphenidate had better cognition and were able to work more hours. Patients
      tolerated methylphenidate well, and the majority felt better and wanted to
      continue treatment.

PMID- 24445758
TI  - Journey to Oz in search of a remedy for fatigue.

PMID- 24445760
TI  - Expanded use trials-are there better approaches to minimize adverse consequences
      to the clinical trials program?

PMID- 24445759
TI  - A single-arm, open-label, expanded access study of vemurafenib in patients with
      metastatic melanoma in the United States.
AB  - PURPOSE: This open-label, multicenter study was designed to allow access to
      vemurafenib for patients with metastatic melanoma, bridging the time between end
      of enrollment in the phase III registration trial (December 2010) and commercial
      availability following US Food and Drug Administration approval of vemurafenib
      for the treatment of unresectable or metastatic BRAF-mutated melanoma (August
      2011). PATIENTS AND METHODS: Eligible patients had metastatic melanoma with a
      BRAF mutation (detected by the cobas 4800 BRAF V600 Mutation Test). Unlike
      previous vemurafenib trials, patients with poor performance status (PS) and
      treated brain metastases were permitted. Enrolled patients received oral
      vemurafenib 960 mg twice daily. RESULTS: Of 374 patients enrolled at 29 US sites
      (December 2010 to October 2011), 371 patients received vemurafenib and were
      followed up for a median of 2.8 months (the study had a prespecified end upon
      vemurafenib approval and commercial availability). At baseline, most patients
      (75%) had stage M1c disease, and 19% had an Eastern Cooperative Oncology Group PS
      of 2 or 3; 72% of patients had received prior systemic therapy for metastatic
      melanoma, 27% received prior ipilimumab, and 29% radiotherapy for prior brain
      metastases. Because reassessment data to confirm response were not available for
      most patients, point estimates of objective response rate (ORR) are reported.
      Among 241 efficacy-evaluable patients, the ORR was 54% (median time to response,
      1.9 months). The ORR in non-central nervous system sites in patients with
      previously treated brain metastases (n = 68) was 53%. The ORR in prior ipilimumab
      treated patients (n = 68) was 52%. For patients with PS of 0 or 1 (n = 210) and 2
      or 3 (n = 31), the ORRs were 55%, and 42%, respectively. The safety profile
      observed was consistent with that reported in previous studies. The number of
      patients with grade 3 or 4 treatment-related adverse events was higher in
      patients with PS 2 or 3 than in those with PS 0 or 1 (10% vs. 5%, respectively).
      Adverse events requiring a dose reduction (at least 1 level) occurred in 11% of
      patients, and 9 patients (2%) experienced events leading to vemurafenib
      withdrawal, including 2 with repeated QT interval prolongation. DISCUSSION: This
      study confirmed the established rapid and high tumor response rate achievable
      with vemurafenib in BRAF mutation-positive metastatic melanoma. Several groups
      not included in previous studies, including patients with previously treated
      brain metastases, Eastern Cooperative Oncology Group PS 2 to 3, or previous
      ipilimumab treatment had benefitted from vemurafenib similar to the overall
      population. No new safety signals were detected.

PMID- 24445761
TI  - Acute palliative care units: an essential component of the science of caring.

PMID- 24445762
TI  - From the guest editor: into the era of personalized cancer diagnostics.

PMID- 24445763
TI  - Current and proposed molecular diagnostics in a genitourinary service line
      laboratory at a tertiary clinical institution.
AB  - The idea that detailed knowledge of molecular oncogenesis will drive diagnostic,
      prognostic, and therapeutic clinical decision making in an increasingly
      multidisciplinary practice of oncologic care has been anticipated for many years.
      With the recent rapid advancement in our understanding of the molecular
      underpinnings of genitourinary malignancies, this concept is now starting to take
      shape in the fields of prostate, kidney, bladder, testicular, and penile cancer.
      Such breakthroughs necessitate the development of robust clinical-grade assays
      that can be quickly made available for patients to facilitate diagnosis in
      challenging cases, risk-stratify patients for subsequent clinical management,
      select the appropriate targeted therapy from among increasingly diverse and
      numerous options, and enroll patients in advanced clinical trials. This rapid
      translation of basic and clinical cancer research requires a streamlined,
      multidisciplinary approach to clinical assay development, termed here the
      molecular diagnostics service line laboratory. In this review, we summarize the
      current state and explore the future of molecular diagnostics in genitourinary
      oncology to conceptualize a genitourinary service line laboratory at a tertiary
      clinical institution. 

PMID- 24445764
TI  - Genetics of diffuse large B-cell lymphoma: paving a path to personalized
      medicine.
AB  - Diffuse large B-cell lymphoma, the most common type of lymphoma in Western
      countries, remains incurable in approximately 40% of patients. Over the past
      decade, nascent molecular technologies have led to the discovery of many of the
      genetic events underlying the pathogenesis of this group of diseases. Whether by
      defining gene signatures that subclassify diffuse large B-cell lymphoma into
      subgroups, dysregulation of key cellular pathways, or specific mutations, we are
      approaching an era in which personalized diagnostics, prognostication, and
      therapy are imminent. 

PMID- 24445765
TI  - Molecular diagnostics of T-cell lymphoproliferative disorders.
AB  - T-cell neoplasms include both mature T-cell leukemias and lymphomas and immature
      proliferations of precursor T cells. Molecular laboratories routinely assay
      suspected T-cell proliferations for evidence of clonality. In addition, some T
      cell neoplasms are characterized by recurrent structural abnormalities that can
      be readily identified by such techniques as fluorescence in situ hybridization.
      New massively parallel sequencing technologies have led to the identification of
      numerous recurrent gene mutations in T-cell neoplasms. These findings are
      reviewed. As new technologies become implemented in molecular diagnostic
      laboratories and as targeted therapies are developed, it is anticipated that more
      extensive genomic characterization of T-cell neoplasms will be routinely
      performed in the future. 

PMID- 24445767
TI  - Molecular genetics of gliomas.
AB  - Diffusely infiltrating gliomas are the most common primary brain tumors and
      include astrocytomas, oligodendrogliomas, and oligoastrocytomas of grades II and
      III and glioblastoma (GBM), grade IV. Histologic classification is increasingly
      aided by molecular genetic studies, which assist in the diagnosis and provide
      prognostic and predictive value. Mutations in IDH1 are frequent in grades II and
      III astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary
      GBMs. IDH1-mutated diffuse gliomas are distinct from their IDH1 wild-type
      counterparts based on clinical features, growth rates, and concurrent genomic
      alterations. Grades II and III astrocytomas, as well as secondary GBMs are
      characterized by IDH1, TP53, and ATRX mutations, whereas oligodendrogliomas most
      frequently harbor codeletion of 1p/19q and mutations in CIC, FUBP1, and the TERT
      promoter. Primary GBMs frequently show molecular alterations in EGFR, PDGFRA,
      PTEN, TP53, NF1, and CDKN2A/B, as well as TERT promoter mutations, but not IDH
      mutations. Pediatric GBMs have a distinctive molecular pathogenesis, as H3F3A and
      DAXX mutations are frequent, and their gene expression profile is different than
      adult GBMs. Other lower-grade gliomas of childhood, such as pilocytic astrocytoma
      and pleomorphic xanthoastrocytoma, are characterized by BRAF mutations or
      activating gene rearrangements involving BRAF. 

PMID- 24445766
TI  - Genetics of myeloproliferative neoplasms.
AB  - In the last decade, genomic studies have identified multiple recurrent somatic
      mutations in myeloproliferative neoplasms (MPNs). Beginning with the discovery of
      the JAK2 V617F mutation, multiple additional mutations have been found that
      constitutively activate cell-signaling pathways, including MPL, CBL, and LNK.
      Furthermore, several classes of epigenetic modifiers have also been identified,
      in patients with MPN, revealing a requirement for mutations in other pathways to
      cooperate with JAK-STAT pathway mutations in MPN pathogenesis. Mutations in the
      de novo DNA methylation protein, DNMT3A, demethylation machinery, TET2 and
      related IDH1/2 production of oncometabolite 2-hydroxygluterate, and polycomb
      complex proteins EZH2 and ASXL1 have opened new pathophysiologic clues into these
      diseases. The prognostic relevance of these novel disease alleles remains an
      important area of investigation, and clinical trials are currently underway to
      determine if these findings represent tractable therapeutic targets, either
      alone, or in combination with JAK2 inhibition. 

PMID- 24445768
TI  - Molecular genetics of soft-tissue sarcomas: a brief overview for clinical
      oncologists.
AB  - Soft-tissue sarcomas (STSs) are a heterogeneous group of tumors with distinct
      lines of differentiation and biologic behavior. Currently, histological analysis
      is still the main diagnostic approach for the classification of STSs. However,
      ancillary molecular genetic methods are becoming increasingly important for
      diagnostic confirmation and therapeutic considerations. Herein, we provide a
      brief overview of clinically relevant molecular abnormalities of STSs for the
      general clinical oncologist. 

PMID- 24445769
TI  - Genetic progression of pancreatic cancer.
AB  - The progression from normal cells to invasive pancreatic ductal adenocarcinoma
      (PDAC) requires the accumulation of multiple inherited or acquired mutations.
      Activating point mutations in the KRAS oncogene are prevalent in pancreatic
      cancer and result in the stimulation of several pathways including the RAF
      mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase
      pathway. Other genetic alterations, including telomere shortening and the
      inactivation of tumor suppressor genes such as CDKN2A, TP53, and SMAD4, which
      encode p16, p53, and SMAD4, respectively, also contribute to the progression of
      pancreatic cancer. These, and other genetic events, can present at different
      stages in the development of PDAC at histologically defined precursor lesions
      known as pancreatic intraepithelial neoplasia, intraductal papillary mucinous
      neoplasms, or mucinous cystic neoplasms. Each precursor lesion represents
      alternate routes to PDAC formation and has a unique presentation and somewhat
      distinct genetic events controlling its development. Despite the advances in the
      understanding of the genetics of PDAC, the prognosis for this cancer remains
      poor, and several important aspects of its pathogenesis must be clarified to
      improve therapeutics, including the timing and method of metastases, as well as
      the relationship of the tumor cells with the desmoplastic stroma, which is a
      characteristic feature of the cancer. This review discusses the principal genetic
      alterations in PDAC and its precursor lesions, including their effects on
      promoting carcinogenesis. 

PMID- 24445770
TI  - Intellectual property and regulation of molecular pathology tests.
AB  - Legal and regulatory issues have assumed heightened importance in molecular
      pathology. Patents on relationships between human gene variants and clinical
      phenotypes, as well as on the underlying gene sequences themselves, have been
      extremely controversial. However, recent Supreme Court decisions appear to have
      rendered invalid these classes of patents. The Clinical Laboratory Improvement
      Amendments of 1988 have been the primary basis for laboratory oversight in the
      United States, whereas the Food and Drug Administration has been responsible for
      regulating in vitro test kits distributed in interstate commerce. However, the
      Food and Drug Administration has recently announced its intention to regulate
      laboratory-developed tests, raising concerns in the laboratory community. This
      article reviews recent developments impacting the legal status of gene patenting
      and oversight of molecular pathology testing in the United States. 

PMID- 24445771
TI  - Genomic oncology education: an urgent need, a new approach.
AB  - Genomic testing has entered oncology practice. With reduced cost and faster
      turnaround times, clinical applications for next-generation sequencing-based
      assays will only continue to increase. As such, there is an urgent need for
      health professional education to allow implementation of these new diagnostic
      tools. However, current medical school, residency, and fellowship training has
      had limited success in educating physicians in the fundamentals of single-gene
      testing, let alone genomic methods. In this review, we describe the novel
      approach the pathology community has taken in genomic education and the potential
      for application to oncology trainees. 

PMID- 24445772
TI  - [News in hodgkin lymphoma therapy].
AB  - Hodgkin lymphoma is a well-known clinico-pathological entity with a stable
      incidence among time accounting for 1200 new cases each year in France. The
      disease is one of the most curable cancer and occurs often in young patients with
      a median age at 33 years, the major clinical symptoms are lymph nodes mostly
      above the diaphragm (mediastinal and supra-clavicular). The diagnosis should be
      suggested with non-specific symptoms such as fever, night sweats, pruritus,
      weight-loss, lymph node, cough.. leading to prescribe routine exams like blood
      test with leucocyte count, erythrocyte sedimentation rate and chest Xray.
      Treatments always include chemotherapy and radiotherapy in localized disease and
      at a low dose only in involved fields. The usually good prognostic of Hodgkin
      lymphoma may not let us forget that there are still deaths in patients with
      refractory or early relapse of the disease. There is still an unmet need is these
      patients and the search for new drugs is essential. 

PMID- 24445773
TI  - Evaluation of menstrual blood stem cells seeded in biocompatible Bombyx mori silk
      fibroin scaffold for cardiac tissue engineering.
AB  - Recently, silk fibroin scaffolds have been introduced as novel and promising
      biomaterials in the field of cardiac tissue engineering. This study was designed
      to compare infiltration, proliferation, and cardiac differentiation potential of
      menstrual blood-derived stem cells (MenSCs) versus bone marrow-derived
      mesenchymal stem cells (BMSCs) in Bombyx mori-derived silk scaffold. Our primary
      data revealed that the fabricated scaffold has mechanical and physical qualities
      suitable for cardiac tissue engineering. The MenSCs tracking in scaffolds using
      immunofluorescent staining and scanning electron microscopy confirmed MenSCs
      attachment, penetration, and distribution within the porous scaffold matrix.
      Based on proliferation assay using propidium iodide DNA quantification, the
      significantly higher level of growth rates of both MenSCs and BMSCs was
      documented in scaffolds than that in two-dimensional culture (p < 0.01). The
      expression level of TNNT2, a bona fide cardiac differentiation marker, in BMSCs
      differentiated on silk scaffolds was markedly higher than those cultured in two
      dimensional culture indicating the improvement of cardiac differentiation in the
      silk scaffolds. Furthermore, differentiated MenSCs exhibited higher expression of
      TNNT2 compared with induced BMSCs. It seems that silk scaffold-seeded MenSCs
      could be viewed as a novel, safe, natural, and accessible construct for cardiac
      tissue engineering.

PMID- 24445774
TI  - Arginine-chitosan- and arginine-polyethylene glycol-conjugated superparamagnetic
      nanoparticles: Preparation, cytotoxicity and controlled-release.
AB  - Iron oxide magnetic nanoparticles (MNPs) can be used in targeted drug delivery
      systems for localized cancer treatment. MNPs coated with biocompatible polymers
      are useful for delivering anticancer drugs. Iron oxide MNPs were synthesized via
      co-precipitation method then coated with either chitosan (CS) or polyethylene
      glycol (PEG) to form CS-MNPs and PEG-MNPs, respectively. Arginine (Arg) was
      loaded onto both coated nanoparticles to form Arg-CS-MNP and Arg-PEG-MNP
      nanocomposites. The X-ray diffraction results for the MNPs and the Arg-CS-MNP and
      Arg-PEG-MNPs nanocomposites indicated that the iron oxide contained pure
      magnetite. The amount of CS and PEG bound to the MNPs were estimated via
      thermogravimetric analysis and confirmed via Fourier transform infrared
      spectroscopy analysis. Arg loading was estimated using UV-vis measurements, which
      yielded values of 5.5% and 11% for the Arg-CS-MNP and Arg-PEG-MNP nanocomposites,
      respectively. The release profile of Arg from the nanocomposites followed a
      pseudo-second-order kinetic model. The cytotoxic effects of the MNPs, Arg-CS
      MNPs, and Arg-PEG-MNPs were evaluated in human cervical carcinoma cells (HeLa),
      mouse embryonic fibroblast cells (3T3) and breast adenocarcinoma cells (MCF-7).
      The results indicate that the MNPs, Arg-CS-MNPs, and Arg-PEG-MNPs do not exhibit
      cytotoxicity toward 3T3 and HeLa cells. However, treatment of the MCF-7 cells
      with the Arg-CS-MNP and Arg-PEG-MNP nanocomposites reduced the cancer cell
      viability with IC50 values of 48.6 and 42.6 ug/mL, respectively, whereas the MNPs
      and free Arg did not affect the viability of the MCF-7 cells.

PMID- 24445775
TI  - Fiber in the treatment and maintenance of inflammatory bowel disease: a
      systematic review of randomized controlled trials.
AB  - BACKGROUND: Dietary fiber may favorably influence fermentation, gastrointestinal
      inflammation, and disease progression in Crohn's disease, ulcerative colitis
      (UC), and pouchitis and offer an attractive therapeutic addition to
      pharmacological treatment. This systematic review appraised data from randomized
      controlled trials of fiber in the management of inflammatory bowel disease.
      METHODS: The review followed Cochrane and PRISMA recommendations. Seven
      electronic databases were searched along with hand searching and contacting
      experts. Inclusion criteria were randomized controlled trials of the effects of
      fiber on clinical endpoints (primarily disease activity for treatment or
      maintenance) or physiological outcomes in patients with inflammatory bowel
      disease. RESULTS: In total, 23 randomized controlled trials fulfilled the
      inclusion criteria (UC, 10; Crohn's disease, 12; and pouchitis, 1) recruiting
      1296 patients. In UC, 3/10 studies reported fiber supplementation to benefit
      disease outcomes. In Crohn's disease, 0/12 studies and in pouchitis 1/1 study
      reported a benefit on disease activity. Despite this, a number of studies
      reported favorable intragroup effects on physiological outcomes including fecal
      butyrate, fecal calprotectin, inflammatory cytokines, microbiota, and
      gastrointestinal symptom indices. Meta-analysis was not possible. CONCLUSIONS:
      There is limited weak evidence for the efficacy of fiber in improving disease
      outcomes in UC and pouchitis. The potential antiinflammatory role of fiber is
      intriguing and merits further investigation in adequately powered clinical
      trials. Excluding overt gastrointestinal obstruction, there was no evidence that
      fiber intake should be restricted in patients with inflammatory bowel disease.

PMID- 24445776
TI  - Adaptive plasticity of Laguncularia racemosa in response to different
      environmental conditions: integrating chemical and biological data by
      chemometrics.
AB  - Mangroves are dynamic environments under constant influence of anthropic
      contaminants. The correlation between environmental contamination levels and
      possible changes in the morphology of plants, evaluated by multivariate
      statistics helps to highlight matching between these variables. This study aimed
      to evaluate the uptake and translocation of metals and metalloids in roots and
      leaves as well as the changes induced in both anatomy and histochemistry of roots
      of Laguncularia racemosa inhabiting two estuaries of Espirito Santo (Brazil) with
      different pollution degrees. The analysis of 14 elements in interstitial water,
      sediments and plants followed by multivariate statistics, allowed the
      differentiation of studied sites, showing good match between levels of elements
      in the environment with the corresponding in plants. L. racemosa showed
      variations in their root anatomy in different collection areas, with highest
      values of cortex/vascular cylinder ratio, periderm thickness and air gap area in
      Vitoria Bay, the most polluted sampling area. These three parameters were also
      important to differentiate the mangrove areas by linear discriminant analysis.
      The development stage of aerenchyma in roots reflected the oxygen availability in
      the water, being found a negative correlation between these variables. The
      combined use of chemical and biological analyses responded quite well to
      different pollution scenarios, matching morphological responses to physical and
      chemical parameters, measured at different partitions within the estuary. Thus,
      L. racemosa can be confirmed as a reliable sentinel plant for biomonitoring of
      estuaries impacted by anthropic pollution. 

PMID- 24445777
TI  - Maspin is not required for embryonic development or tumour suppression.
AB  - Maspin (SERPINB5) is accepted as an important tumour suppressor lost in many
      cancers. Consistent with a critical role in development or differentiation maspin
      knockout mice die during early embryogenesis, yet clinical data conflict on the
      prognostic utility of maspin expression. Here to reconcile these findings we made
      conditional knockout mice. Surprisingly, maspin knockout embryos develop into
      overtly normal animals. Contrary to original reports, maspin re-expression does
      not inhibit tumour growth or metastasis in vivo, or influence cell migration,
      invasion or survival in vitro. Bioinformatic analyses reveal that maspin is not
      commonly under-expressed in cancer, and that perturbation of genes near maspin
      may in fact explain poor survival in certain patient cohorts with low maspin
      expression. 

PMID- 24445778
TI  - Robust global microRNA expression profiling using next-generation sequencing
      technologies.
AB  - miRNAs are a class of regulatory molecules involved in a wide range of cellular
      functions, including growth, development and apoptosis. Given their widespread
      roles in biological processes, understanding their patterns of expression in
      normal and diseased states will provide insights into the consequences of
      aberrant expression. As such, global miRNA expression profiling of human
      malignancies is gaining popularity in both basic and clinically driven research.
      However, to date, the majority of such analyses have used microarrays and
      quantitative real-time PCR. With the introduction of digital count technologies,
      such as next-generation sequencing (NGS) and the NanoString nCounter System, we
      have at our disposal many more options. To make effective use of these different
      platforms, the strengths and pitfalls of several miRNA profiling technologies
      were assessed, including a microarray platform, NGS technologies and the
      NanoString nCounter System. Overall, NGS had the greatest detection sensitivity,
      largest dynamic range of detection and highest accuracy in differential
      expression analysis when compared with gold-standard quantitative real-time PCR.
      Its technical reproducibility was high, with intrasample correlations of at least
      0.95 in all cases. Furthermore, miRNA analysis of formalin-fixed, paraffin
      embedded (FFPE) tissue was also evaluated. Expression profiles between paired
      frozen and FFPE samples were similar, with Spearman's rho>0.93. These results
      show the superior sensitivity, accuracy and robustness of NGS for the
      comprehensive profiling of miRNAs in both frozen and FFPE tissues. 

PMID- 24445779
TI  - Choroid artery occlusion after treatment of ICA termination aneurysm: was it
      caused by stent induced vasospasm?

PMID- 24445781
TI  - [Not Available].

PMID- 24445780
TI  - Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with
      systemic lupus erythematosus in a Taiwanese population.
AB  - Toll-like receptors (TLRs), as innate immunity sensors, play critical roles in
      immune responses. Six SNPs of TLR3, TLR7, and TLR8 were genotyped to determine
      their associations with systemic lupus erythematosus (SLE) and clinical
      manifestations of SLE. TLR7 SNP rs3853839 was independently associated with SLE
      susceptibility in females (G vs. C: p = 0.0051). TLR7 rs3853839-G (G vs. C: p =
      0.0100) and TLR8 rs3764880-G (recessive model: p = 0.0173; additive model: p =
      0.0161) were associated with pericardial effusion in females relative to healthy
      females. Anti-SSA positive cases were more likely to have the dominant TLR7
      rs179010-T allele than normal controls (p = 0.0435). TLR3 rs3775296-T was
      associated with photosensitivity (p = 0.0020) and anemia (p = 0.0082). The "G-G"
      haplotype of TLR7 rs3853839 and TLR8 rs3764880 increased risk of SLE in females
      (age adjusted p = 0.0032). These findings suggest that TLR variations that modify
      gene expression affect risk for SLE susceptibility, clinical phenotype
      development, and production of autoantibodies. 

PMID- 24445782
TI  - [The use of cross-sectional imaging modalities in the diagnosis of valvular heart
      disease].
AB  - Exact visualization of valve morphology seems to be possible with the cross
      sectional imaging modalities, magnetic resonance imaging (MRI) and the recently
      introduced technique of multidetector computed tomography (MDCT). These
      techniques are used, if other non-invasive imaging modalities, like
      echocardiography, fail or provide only insufficient information. This commonly
      occurs in the assessment of right ventricular valves. Quantification of valve
      stenosis is possible by calculating valve orifice area, which can be performed
      with MRI and MDCT. An estimation of the instantaneous peak gradient can only be
      achieved by MR flow measurements. MR flow measurement is a reliable method to
      quantify the degree of mild to moderate stenoses. Quantification of valve
      regurgitation is possible by measurement of the regurgitation fraction with MR
      flow measurements as well as with MR volumetry/CT volumetry. But only the MR flow
      measurement is suitable for the quantification of valve regurgitation in patients
      with multiple valves involved or cardiac shunting. MRI and probably MDCT are the
      most reliable methods in the evaluation of ventricular volumes and therefore
      suitable for the follow-up in patients with valvular heart disease, because
      changes in volumes are important for therapeutic decisions in these patients. The
      crucial advantages of MRI compared to CT in the diagnostic of valvular heart
      diseases however are the absence of radiation exposure, the possibility of
      quantitative evaluation of valves function using flow measurements and the higher
      temporal resolution as compared to MDCT. 

PMID- 24445783
TI  - [Current standard in diagnosis and therapy of heart valve lesions].
AB  - We present a survey of the current standard in diagnosis and therapy of the most
      frequent heart valve lesions. During the last 50 years there has been a dramatic
      shift concerning the etiology of valve lesions with a rise of the agedependent
      degenerative towards rheumatic valve diseases. The aim of the diagnostic
      evaluation of valve lesions is primarily the clinical and hemodynamic grading of
      the severity of the valve disease, the recognition of relevant coexisting cardiac
      and extracardiac diseases and furthermore, an optimal timing of surgery in close
      correlation with the cardiac surgeons. 

PMID- 24445784
TI  - [Prophylaxis of bacterial endocarditis].
AB  - An effective prophylaxis against bacterial endocarditis is necessary in patients
      at risk. In all medical specialities, a lack of information about the importance
      concerning an antibiotic prophylaxis of bacterial endocarditis remains. Among
      other institutions the American Heart Association has updated recommendations for
      the prevention of bacterial endocarditis in order to more clearly define when
      prophylaxis is or is not recommended, improve practitioner and patient
      compliance, and reduce cost as well as potential side effects. 

PMID- 24445785
TI  - [Long-term results after surgery for acute aortic endocarditis].
AB  - Late results after surgery for acute infectious aortic endocarditis using
      allografts are compared with those achieved with bioprostheses or mechanical
      heart valves. Cryopreserved allografts were used in 74 (22 %) and prosthetic
      heart valve in 262 out of 336 (78 %) patients presenting acute aortic
      endocarditis. Prosthetic (p = 0.001) and destructive endocarditis (p = 0.001)
      were more frequent in patients receiving allografts. Mean follow-up time was 6.6
      +/- 4 years (range, 3 to 28 years). The 30-daymortality was 19 % for allograft
      patients and 6 % for those receiving prosthetic heart valves (p = 0.002). Early
      reoperation, postoperative renal failure and sepsis did not differ between
      groups. After 20 years, actuarial survival was 60 % for mechanical heart valves,
      44 % for bioprosthesis and 38 % for allografts (p = 0.003), reoperation was
      unnecessary in 52 % of mechanical heart valves and 10 % of bioprostheses and
      allografts (p = 0.0007). Acute infection at the time of operation (p = 0.0001),
      redo surgery (p = 0.0006), staphylococci (p = 0.0003), older age (p = 0.004) and
      mitral valve involvement (p = 0.004) were risk factors for late death,
      irrespective of preoperative antibiotic treatment and type of prosthesis used. A
      longer bypass and aortic cross-clamp time predicted early (p = 0.0001) and late
      survival (p = 0.0001), independently. Destructive aortic endocarditis has a poor
      long-term outcome irrespective of the use of allografts. Acute infection at the
      time of surgery predicted early and late death; however, surgery is indicated
      prior to secondary involvement of the mitral valve. The duration of preoperative
      antibiotic treatment did not affect outcome. A thorough surgical technique
      directly influences early and late survival. 

PMID- 24445786
TI  - [Etiology of degenerative disease of the tri-leaflet aortic valve: a simple
      explanation for a complex problem].
AB  - Risk factors for both atherosclerotic aortic wall disease and degenerative
      disease of the trileaflet aortic valve are very similar if not identical. This
      correlation grows even stronger as the person advances in years. Because of this,
      it is the prevailing view that sclerosis of the tri-leaflet aortic valve is a
      disease similar in etiology with sclerosis of the aortic wall. In other words,
      degenerative aortic valve disease is atherosclerosis of the aortic valve. Our
      studies challenge these views. The aortic valve is a functional assembly composed
      of the three cusps, corresponding sinuses, and the sinotubular junction,
      characterized not only by morphological features but also its functional
      properties, which together create an environment that is optimal for distribution
      of diastolic pressure load, and assures proper and timely valve opening and
      closure. Our experiments also demonstrate that loss of aortic wall compliance at
      the level of the sinuses leads to significant flexion stress in the aortic
      leaflets and it is likely to start a chain of events, which begins with
      mechanical damage to the leaflet microstructure then continues to more evident
      sclerosis, and finally ends in gross distortion and/or calcification of the
      cusps.The loss of the "pull-andrelease" process may also play a part in
      disintegration of bioprosthetic valves and in degeneration of native aortic
      valves encased in noncompliant prostheses. 

PMID- 24445787
TI  - [Mechanical versus biological heart valves].
AB  - Since the first successful heart valve replacement procedures were performed in
      the 1950s, a multitude of different heart valves have been developed and
      implanted. This review offers a structured overview of the most important
      mechanical and biological heart valves with special regard to the individual
      indications of mechanical versus biological heart valve replacement and to
      possible postoperative complications. 

PMID- 24445788
TI  - [Patient adapted valve selection: biological vs. mechanical heart valve
      replacement in aortic valve diseases].
AB  - Since the first aortic valve replacement performed by Harken in 1960, the
      operation of aortic valve disease by replacing the native valve with a heart
      valve prosthesis has become one of the most frequently performed procedures in
      cardiac surgery. For valve replacement there are biological (xenografts and
      homografts) and mechanical heart valve prostheses available. When choosing the
      most suitable prosthesis the limited durability of a biological prosthesis and
      the risks of lifelong anticoagulation for a mechanical prosthesis have to be
      balanced.In this article the indication for operation of aortic valve stenosis
      and aortic regurgitation are discussed first. Based on the literature of the last
      2 years the advantages and disadvantages of mechanical and biological heart valve
      prostheses (xenograft, homograft and ROSS procedure) are discussed. In addition
      rarely used techniques like aortic valve reconstruction are presented.Due to the
      fact that a biological prosthesis has a durability of 12-15 years and the risk of
      bleeding complications under anticoagulation grows with increasing age, the
      choice of a biological prosthesis can be recommended from the age of 65 years.
      Results of long-term studies at to whether this limit can be diminished by using
      a stentless biological prosthesis have to be awaited. 

PMID- 24445789
TI  - [Risk of perioperative mortality and complications following biological aortic
      valve replacement in elderly patients: stented vs unstented bioprotheses].
AB  - Recently published studies suggest that the hemodynamic advantage of stentless
      bioprostheses in comparison to stented bioprostheses positively influence the
      long-term survival after aortic valve replacement. However, the more complex and
      time consuming implantation technique may increase the risk of operative death.
      Between April 1996 and September 2000, 201 patients with the mean age of 75 +/- 5
      years underwent aortic valve replacement (AVR) with a stentless Medtronic
      Freestyle Bioprothesis (FP) and 166 patients with a mean age of 77 +/- 5 years
      received a stented Medtronic Mosaic Biopros thesis (MP). Patients requiring
      concomitant procedures other than coronary artery bypass grafting (CABG) were
      excluded. The operative mortality was 3.5% after AVR with the FP and 6% after AVR
      with the MP. Multiple logistic regression analysis considering the different
      patient populations revealed no increased risk of operative death after AVR with
      FB (p = 0.46). Previously heart operations (p = 0.046) and emergency operation (p
      = 0.022) were risk factors for operative death after AVR with the biological
      bioprostheses. The risk for postoperatively neurological impairment (p = 0.15)
      and other complications (p = 0.46) was furthermore not increased after
      implantation of a Freestyle stentless valve. The risk of delayed mobilization (p
      < 0.001) was 2.4-fold increased for patients after AVR with the Freestyle valve.
      A positive influence on survival due to the implantation of a stentless Freestyle
      valve could not be shown within the observed period. However, in spite of the
      more complex and time-consuming operation technique, the risk of operative death
      and postoperative complications is not increased after aortic valve replacement
      with the stentless FB. 

PMID- 24445790
TI  - [Multiple-valve disease].
AB  - After more than 40 years of heart valve surgery, the indication for double valve
      procedures still represents a problem in the presence of an obviously leading
      single valve disease. If the isolated valves do not already represent a clear
      indication for surgery then this situation is the best example for a good deal of
      thought in cardiac surgery and discussion with competent cardiologists. 

PMID- 24445791
TI  - [Timing of reoperation of degenerated aortic and mitral bioprostheses].
AB  - Reoperative surgery for degenerated aortic and mitral valve bioprostheses has a
      considerable mortality. This study compares life expectancy, mode of failure and
      predictors for emergency reoperation and reoperative mortality between
      degenerated aortic and mitral bioprostheses. A total of 265 bioprosthetic valve
      patients, 172 aortic and 93 mitral patients, were followed to assess the time
      period between first and redo valve replacement. Mean life expectancy for aortic
      bioprostheses was 10.4 +/- 4.3 (2 to 28.6) years, whereas it was 10.0 +/- 3.7
      (0.9 to 20) years for mitral bioprostheses (group M). Emergency reoperation had
      to be performed in 31/172 group A (18 %) and 16/93 group M (17 %) patients. In
      group A, the reoperative mortality was 5.2 %; it was 1.4 % for elective and 22.6
      % for emergency reoperation (p < 0.0001; OR = 20.3). Reoperative mortality in
      group M patients was 5.4 % and did not differ between elective and emergency
      surgery. Group A patients who died at reoperation had higher transvalvular
      gradients before the first operation (p = 0.007), received smaller sized
      bioprostheses (p = 0.03) and had a higher incidence of coronary artery disease (p
      = 0.001) and pulmonary artery hypertension (p = 0.009) acquired during the
      interval. Endocarditis being the reason for primary surgery (p = 0.004),
      postoperative pneumonia after the first procedure (p = 0.005), pulmonary artery
      hypertension (p = 0.0004), later recurrence of symptoms of valve degeneration (p
      = 0.04), acute onset of bioprosthetic regurgitation (p = 0.00002) and a lower
      left ventricular ejection fraction (p = 0.03) were risk factor for emergency
      surgery. There were no predictors of reoperative mortality identified in mitral
      valve patients. The life expectancy of aortic and mitral bioprostheses is
      acceptable even in a relatively young patient population (mean age 46 +/- 13 in
      group A and 45 +/- 12 years in group M patients). Patients with degenerated
      aortic bioprostheses undergoing emergency reoperation have an extraordinary high
      reoperative mortality. They can be identified as patients who had a history of
      endocarditis and higher transvalvular gradients prior to the first operation, who
      received smaller sized bioprostheses and acquired coronary artery disease and
      pulmonary artery hypertension during the interval. Thus, emergency reoperation is
      preventable, increasing overall life expectancy of patients with bioprostheses.
      There were no risk factors for reoperative mortality identified in bioprosthetic
      mitral valve patients. 

PMID- 24445792
TI  - [Mitral valve repair versus mitral valve replacement].
AB  - Over the past 40 years mitral valve surgery has changed dramatically. After
      initial enthusiasm with the introduction of valve prostheses in the 1960s, a
      renewed interest in repair techniques began in the 1970s with the introduction of
      annuloplasty rings. These repair techniques revealed that the integrity of the
      subvalvular apparatus plays an important role in left ventricular function. When
      considering the major series comparing early and late results of mitral valve
      repair versus prosthetic mitral valve replacement, operative mortality rate is
      lower for patients with mitral valve repair. Long-term results also show a
      superior survival rate after mitral valve reconstruction. In addition, several
      problems can occur with the prosthetic valve, such as thromboembolism and
      endocarditis. All of these factors favor valve repair over replacement. The
      success of mitral valve repair depends on many factors: etiology of the mitral
      valve disease and the resultant pathomorphology of the valve, patient's
      circumstances such as age or contraindication for anticoagulation, and the
      experience of the surgeon. The decision whether to repair or replace the mitral
      valve depends on these factors. Data in the literature and in large collective
      databases reflect the advantages of mitral valve repair, with over 75 % of
      current mitral valve surgeries being repairs.In the past 5 years the exposure of
      the mitral valve through a right lateral minithoracotomy using video assistance
      has developed into a widespread technique. This approach allows complex mitral
      valve repair as well as mitral valve replacement even with biological stentless
      prostheses, with decreased morbidity. The addition of radiofrequency ablation for
      restoration of sinus rhythm enhances the outcome after mitral valve surgery, and
      can also be easily performed through a minithoracotomy technique. 

PMID- 24445793
TI  - [Surgery in terminal mitral valve disease].
AB  - In the past few years both the spectrum of mitral valve diseases leading to
      surgery and the surgical techniques have changed. We present our experience with
      the preservation of the subvalvular apparatus when mitral valve replacement is
      performed. In addition to preservation of the subvalvular apparatus of the
      posterior mitral leaflet, five techniques of subvalvular preservation are
      described. We conclude that mitral valve replacement should always aim at
      preservation of the subvalvular structures. The surgical method of choice in
      cases of isolated mitral valve insufficiency is mitral valve reconstruction.
      Treatment of associated atrial fibrillation, preferably by radiofrequency
      ablation, should always be performed concomitantly. Surgery of the mitral valve
      represents a palliative operation in selected patients with terminal
      cardiomyopathy. 

PMID- 24445794
TI  - [Replacement of the ascending aorta with aortic valve reimplantation -
      indication, technique, and results].
AB  - The main cause of aortic valve insufficiency is a dilatation of the sinotubular
      junction in patients with an ascending aortic aneurysm. Morphologically preserved
      aortic valve cusps represent an ideal condition for preservation and
      reconstruction of the aortic valve with an simultaneous replacement of the
      ascending aorta with a Dacron graft. This report presents the results of 140
      patients, who underwent such surgery since 1993 in our institution. Indications
      for surgery, operative technique and different outcome parameters are discussed.
      Intra- and perioperative morbidity and mortality are low and quality of life
      excellent. Reoperation due to progressive aortic valve insufficiency was
      necessary in 2.1% of patients during follow-up. When compared with the standard
      operation (composite replacement utilizing a mechanical valve), patients with
      aortic valve reconstruction demonstrate similar results with regard to hospital
      stay and functional improvement. However, bleeding complications and
      thromboembolic events are significantly reduced in patients undergoing valve
      reconstruction. Due to these long-term results combined with excellent stress
      hemodynamics and improvement in LV function, aortic valve reconstruction
      currently represents our standard operative strategy in this patient group. 

PMID- 24445795
TI  - [Perioperative complications after heart valve replacement].
AB  - These days, the majority of perioperative complications resulting from operations
      on heart valves are more a consequence of the increasing age and morbidity of the
      patients and, despite all cardiac surgical and intensive care innovations, are
      still more the effect of the procedure on the other organ systems of the patient
      than being purely of a surgical nature. The surgical short - and long-term
      results after heart valve operations are significantly influenced by the early
      detection and adequate management of these manifold complications. 

PMID- 24445796
TI  - [Turbulence and high intensity transient signals (HITS) as a parameter for
      optimum orientation of mechanical heart valves].
AB  - BACKGROUND: In previous studies, the impact of valve orientation on the
      hemodynamic performance of mechanical aortic valves has been demonstrated. This
      study investigates Turbulence (RNS values) and High Intensity Transient Signals
      (HITS) as a new and objective parameter for hemodynamics in various orientations
      of Medtronic Hall (MH) and St. Jude Medical (SJM) aortic valves. METHODS:
      Rotation devices carrying a MH or SJM valve were implanted into four pigs. The
      device allowed valve rotation without reopening the aorta. In various
      orientations, turbulent shear stresses (RNS values) and HITS were measured.
      RESULTS: RNS and HITS changed for both valve designs in the different
      orientations, with superior results for the MH in the hemodynamically best
      orientation. Downstream turbulence (RNS) and HITS varied in the same direction,
      but a one to one correlation was not observed. CONCLUSIONS: RNS and HITS vary
      with respect to valve orientation and design with superior results for the
      tilting disc valve. Both MH and SJM valves showed lower turbulence and HITS
      counts in their hemodynamically best orientations. HITS were related to
      downstream turbulence and the hemodynamic performance of the mechanical aortic
      valves.

PMID- 24445797
TI  - [Marfan syndrome and valvular disease].
AB  - Marfan syndrome is a hereditary disease of the connective tissue with increased
      mortality mostly due to changes of the cardiovascular system. We describe our
      experience with the surgical treatment of 243 patients with Marfan syndrome and
      cardiovascular complications. We report the results of treatment of annulo-aortal
      ectasia using the classical surgical methods of Bentall DeBono and Cabrol and the
      method for preservation of the native aortic valve and concomitant surgery of the
      mitral valve. Reconstruction or replacement of the mitral valve is mainly based
      on the classical indications. Preservation of the native aortic valve and
      reconstruction of the mitral valve in patients with Marfan syndrome is possible
      but the long-term results are still unknown. 

PMID- 24445798
TI  - [Current recommendations for prevention of thromboembolic events in patients with
      heart valve prostheses].
AB  - Within the last few years, marked progress has been made in the prevention of
      thromboembolic events in patients with mechanical heart valves. Thus, therapy has
      become more effective and is associated with less risk. This includes a number of
      developments like the introduction of the internationalized, normalized ratio
      (INR) for determination of the intensity of anticoagulation, the concept of a
      risk factor-adjusted, prosthesis specific, individualized indication for and
      intensity of anticoagulation and the possibility for self-determination of
      anticoagulation intensity by the patient. Prospective, randomized studies on the
      effect of different intensities of anticoagulation allowed definitions of
      individualized anticoagulation target levels and were the basis for guidelines on
      clinical management of anticoagulation. In spite of this progress, thromboembolic
      complications and anticoagulation associated bleedings are still the most
      frequent complications after valve replacement. The guidelines published by the
      professional societies on anticoagulation should be followed more closely in
      daily clinical practice. The management of oral anticoagulant treatment can be
      improved by following the concept of a risk factor-adjusted indication for and
      intensity of oral anticoagulant treatment as well as the use of the INR for
      monitoring the intensity of anticoagulation. Intensive education of the patient,
      implementation of self-testing by suitable patients and increasing the frequency
      of testing can further contribute to improvement. 

PMID- 24445799
TI  - [INR Self-management after mechanical heart valve replacement: ESCAT (Early Self
      Controlled Anticoagulation Trial)].
AB  - Severe thromboembolic and hemorrhagic complications following mechanical heart
      valve replacement essentially occur due to intense oral anticoagulation and
      fluctuating individual INR values around the target range. INR self-management
      can help to minimize these fluctuations. Beginning this therapeutic control
      immediately after mechanical heart valve replacement further reduces
      anticoagulant-induced complications. Included in the study were 1200 patients.
      The quality of oral anticoagulation also improved through INR self-management.
      Over an observation period of two years, nearly 80 % of INR values recorded by
      the patients themselves were within the target therapeutic range of 2.5-4.5. This
      corresponds to a high significance of p < = 0.001 in favor of INR self
      management. Only 64.9 % of INR values monitored by family practitioners were
      within the desired range. The results differed slightly in quality between
      patient groups with different levels of training (comprehensive, secondary
      modern, grammar with or without university). Of patients trained in INR self
      management following mechanical heart valve replacement, 91.7 % maintained their
      competence in this technique throughout the entire follow-up period. Only 8.3 %
      of those trained immediately after surgery were unable to continue with INR self
      management. 

PMID- 24445800
TI  - [Anticoagulation of pregnant women with a mechanical heart valve prosthesis].
AB  - Patients with a mechanical heart valve prosthesis (MHVP) are usually
      anticoagulated with oral anticoagulants (OAC) to prevent thromboembolic
      complications. Considering the paucity of published data, the management of women
      with MHVP of childbearing age, who wish to become pregnant, still remains
      difficult and complicated. OAC may cause embryopathy during the first trimester,
      while neurologic complications, stillbirth and fetal death may appear during the
      second and third trimester. While the application of unfractionated heparin (UFH)
      in pregnant patients with MHVP may fail to prevent thromboembolic complications
      even with therapeutic dosage, only little is known about the application of body
      weight adjusted therapeutic dosages of low molecular weight heparin (LMWH). We
      report on 8 female patients, 7 with MHVP, one with atrial fibrillation, who were
      treated with LMWH during the whole pregnancy. No malformations or major bleeding
      complications were observed, no valve thrombosis or thromboembolic complications
      occurred. Three patients developed moderate heart failure during the third
      trimester, which resolved after treatment. In three patients, cesarean section
      was necessary, while the other five patients delivered spontaneously.Therefore,
      anticoagulation with body weight adjusted LMWH seems to be an alternative, safe
      and efficient treatment for pregnant women with MHVP. Prospective, randomized
      studies are needed to further evaluate this new therapeutic approach. The
      underlying heart disease represents a serious comorbid condition that requires
      continuous interdisciplinary monitoring. 

PMID- 24445801
TI  - Alzheimer disease: chaperone protein clusterin is involved in amyloid-beta
      associated entorhinal atrophy in early AD.

PMID- 24445802
TI  - Predicting DNA methylation level across human tissues.
AB  - Differences in methylation across tissues are critical to cell differentiation
      and are key to understanding the role of epigenetics in complex diseases. In this
      investigation, we found that locus-specific methylation differences between
      tissues are highly consistent across individuals. We developed a novel
      statistical model to predict locus-specific methylation in target tissue based on
      methylation in surrogate tissue. The method was evaluated in publicly available
      data and in two studies using the latest IlluminaBeadChips: a childhood asthma
      study with methylation measured in both peripheral blood leukocytes (PBL) and
      lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with
      methylation in PBL, atrium and artery. We found that our method can greatly
      improve accuracy of cross-tissue prediction at CpG sites that are variable in the
      target tissue [R(2) increases from 0.38 (original R(2) between tissues) to 0.89
      for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81
      to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and
      confirmed using cross-study prediction]. An extended model with multiple CpGs
      further improved performance. Our results suggest that large-scale epidemiology
      studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated
      to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium)
      and might enable non-invasive disease screening using epigenetic profiles. 

PMID- 24445803
TI  - The amino terminal extension of mammalian mitochondrial RNA polymerase ensures
      promoter specific transcription initiation.
AB  - Mammalian mitochondrial transcription is executed by a single subunit
      mitochondrial RNA polymerase (Polrmt) and its two accessory factors,
      mitochondrial transcription factors A and B2 (Tfam and Tfb2m). Polrmt is
      structurally related to single-subunit phage RNA polymerases, but it also
      contains a unique N-terminal extension (NTE) of unknown function. We here
      demonstrate that the NTE functions together with Tfam to ensure promoter-specific
      transcription. When the NTE is deleted, Polrmt can initiate transcription in the
      absence of Tfam, both from promoters and non-specific DNA sequences.
      Additionally, when in presence of Tfam and a mitochondrial promoter, the NTE
      deleted mutant has an even higher transcription activity than wild-type
      polymerase, indicating that the NTE functions as an inhibitory domain. Our
      studies lead to a model according to which Tfam specifically recruits wild-type
      Polrmt to promoter sequences, relieving the inhibitory effect of the NTE, as a
      first step in transcription initiation. In the second step, Tfb2m is recruited
      into the complex and transcription is initiated. 

PMID- 24445804
TI  - Synthetic biology tools for programming gene expression without nutritional
      perturbations in Saccharomyces cerevisiae.
AB  - A conditional gene expression system that is fast-acting, is tunable and achieves
      single-gene specificity was recently developed for yeast. A gene placed directly
      downstream of a modified GAL1 promoter containing six Zif268 binding sequences
      (with single nucleotide spacing) was shown to be selectively inducible in the
      presence of beta-estradiol, so long as cells express the artificial transcription
      factor, Z3EV (a fusion of the Zif268 DNA binding domain, the ligand binding
      domain of the human estrogen receptor and viral protein 16). We show the strength
      of Z3EV-responsive promoters can be modified using straightforward design
      principles. By moving Zif268 binding sites toward the transcription start site,
      expression output can be nearly doubled. Despite the reported requirement of
      estrogen receptor dimerization for hormone-dependent activation, a single binding
      site suffices for target gene activation. Target gene expression levels correlate
      with promoter binding site copy number and we engineer a set of inducible
      promoter chassis with different input-output characteristics. Finally, the
      coupling between inducer identity and gene activation is flexible: the ligand
      specificity of Z3EV can be re-programmed to respond to a non-hormone small
      molecule with only five amino acid substitutions in the human estrogen receptor
      domain, which may prove useful for industrial applications. 

PMID- 24445805
TI  - A highly divergent archaeo-eukaryotic primase from the Thermococcus nautilus
      plasmid, pTN2.
AB  - We report the characterization of a DNA primase/polymerase protein (PolpTN2)
      encoded by the pTN2 plasmid from Thermococcus nautilus. Sequence analysis
      revealed that this protein corresponds to a fusion between an N-terminal domain
      homologous to the small catalytic subunit PriS of heterodimeric archaeal and
      eukaryotic primases (AEP) and a C-terminal domain related to their large
      regulatory subunit PriL. This unique domain configuration is not found in other
      virus- and plasmid-encoded primases in which PriS-like domains are typically
      fused to different types of helicases. PolpTN2 exhibited primase, polymerase and
      nucleotidyl transferase activities and specifically incorporates dNTPs, to the
      exclusion of rNTPs. PolpTN2 could efficiently prime DNA synthesis by the T.
      nautilus PolB DNA polymerase, suggesting that it is used in vivo as a primase for
      pTN2 plasmid replication. The N-terminal PriS-like domain of PolpTN2 exhibited
      all activities of the full-length enzyme but was much less efficient in priming
      cellular DNA polymerases. Surprisingly, the N-terminal domain possesses reverse
      transcriptase activity. We speculate that this activity could reflect an
      ancestral function of AEP proteins in the transition from the RNA to the DNA
      world. 

PMID- 24445806
TI  - Scp160p is required for translational efficiency of codon-optimized mRNAs in
      yeast.
AB  - The budding yeast multi-K homology domain RNA-binding protein Scp160p binds to
      >1000 messenger RNAs (mRNAs) and polyribosomes, and its mammalian homolog vigilin
      binds transfer RNAs (tRNAs) and translation elongation factor EF1alpha. Despite
      its implication in translation, studies on Scp160p's molecular function are
      lacking to date. We applied translational profiling approaches and demonstrate
      that the association of a specific subset of mRNAs with ribosomes or heavy
      polysomes depends on Scp160p. Interaction of Scp160p with these mRNAs requires
      the conserved K homology domains 13 and 14. Transfer RNA pairing index analysis
      of Scp160p target mRNAs indicates a high degree of consecutive use of iso
      decoding codons. As shown for one target mRNA encoding the glycoprotein Pry3p,
      Scp160p depletion results in translational downregulation but increased
      association with polysomes, suggesting that it is required for efficient
      translation elongation. Depletion of Scp160p also decreased the relative
      abundance of ribosome-associated tRNAs whose codons show low potential for
      autocorrelation on mRNAs. Conversely, tRNAs with highly autocorrelated codons in
      mRNAs are less impaired. Our data indicate that Scp160p might increase the
      efficiency of tRNA recharge, or prevent diffusion of discharged tRNAs, both of
      which were also proposed to be the likely basis for the translational fitness
      effect of tRNA pairing. 

PMID- 24445808
TI  - Editor's page.

PMID- 24445809
TI  - Nine in 10 GPs believe they are being criticised for political gain, poll shows.

PMID- 24445810
TI  - H-bond and pi-pi stacking directed self-assembly of two-component supramolecular
      nanotubes: tuning length, diameter and wall thickness.
AB  - A series of supramolecular nanotubes with fine-tuned length, diameter and wall
      thickness were obtained from co-assembly of an L-glutamic acid based
      bolaamphiphile (HDGA) and melamine with different molar ratios. The changes in
      tubular nanostructures were found to be dependent on different self-assembly
      mechanisms.

PMID- 24445807
TI  - Engineering of a conditional allele reveals multiple roles of XRN2 in
      Caenorhabditis elegans development and substrate specificity in microRNA
      turnover.
AB  - Although XRN2 proteins are highly conserved eukaryotic 5'->3' exonucleases,
      little is known about their function in animals. Here, we characterize
      Caenorhabditis elegans XRN2, which we find to be a broadly and constitutively
      expressed nuclear protein. An xrn-2 null mutation or loss of XRN2 catalytic
      activity causes a molting defect and early larval arrest. However, by generating
      a conditionally mutant xrn-2ts strain de novo through an approach that may be
      also applicable to other genes of interest, we reveal further functions in
      fertility, during embryogenesis and during additional larval stages. Consistent
      with the known role of XRN2 in controlling microRNA (miRNA) levels, we can
      demonstrate that loss of XRN2 activity stabilizes some rapidly decaying miRNAs.
      Surprisingly, however, other miRNAs continue to decay rapidly in xrn-2ts animals.
      Thus, XRN2 has unanticipated miRNA specificity in vivo, and its diverse
      developmental functions may relate to distinct substrates. Finally, our global
      analysis of miRNA stability during larval stage 1 reveals that miRNA passenger
      strands (miR*s) are substantially less stable than guide strands (miRs),
      supporting the notion that the former are mostly byproducts of biogenesis rather
      than a less abundant functional species. 

PMID- 24445811
TI  - NK cells in hepatitis B virus infection: a potent target for immunotherapy.
AB  - Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious
      agents that lead to liver disease in humans. Hepatocellular carcinoma (HCC) and
      cirrhosis of the liver are the most serious complications arising from prolonged
      forms of hepatitis B. Previous studies demonstrated that patients suffering from
      long-term HBV infections are unable to eradicate HBV from hepatocytes completely.
      The mechanisms responsible for progression of these forms of infection have not
      yet been clarified. However, it seems that there are differences in genetic and
      immunological parameters when comparing patients to subjects who successfully
      clear HBV infections, and these may represent the causes of long-term infection.
      Natural killer (NK) cells, the main innate immune cells that target viral
      infections, play important roles in the eradication of HBV from hepatocytes. NK
      cells carry several stimulatory and inhibitor receptors, and binding of receptors
      with their ligands results in activation and suppression of NK cells,
      respectively. The aim of this review is to address the recent information
      regarding NK cell phenotype, functions and modifications in hepatitis B. This
      review addresses the recent data regarding the roles of NK cells as novel targets
      for immunotherapies that target hepatitis B infection. It also discusses the
      potential to reduce the risk of HCC or cirrhosis of the liver by targeting NK
      cells. 

PMID- 24445812
TI  - Detection and characterization of porcine bocavirus in the United States.
AB  - We screened pigs (n = 203) presenting with respiratory illness or diarrhea for
      porcine bocavirus (PBoV); 88 (43.30 %) were positive by PCR. More positives were
      seen in diarrhea cases (48.7 %) than in respiratory cases (29.1 %). Based on
      phylogenetic analysis of 540 nucleotides of the NS1 gene, the viruses could be
      divided into four possible groups. Group IV sequences did not match any GenBank
      sequences, while groups I, II and III gave matches with PBoV3, PBoV4 and PBoV5,
      respectively. The wide range (70 % to 100 %) of nucleotide (nt) sequence identity
      among strains in this study indicates high genetic diversity among porcine
      bocaviruses.

PMID- 24445813
TI  - Recombinant soybean mosaic virus is prevalent in Chinese soybean fields.
AB  - Recombinant soybean mosaic virus (SMV-R) is a novel strain that has recently been
      identified. SMV-R was first isolated from Chongqing, China, and exhibits
      different pathogenicity on soybeans and common beans compared with normal soybean
      mosaic virus (SMV-N). SMV-R arose from a recombination event between SMV and bean
      common mosaic virus (BCMV) or a BCMV-like virus. In this study, we assessed the
      prevalence of SMV-R in Chinese soybean fields. Polymerase chain reaction results
      showed that SMV-R was common (16.7-60 %) in the central and southern provinces of
      China, based on 206 isolates collected from across China. Furthermore, the
      results from three provinces suggest that SMV-R strains are present in mixed
      infections with other SMV strains. Additionally, the phylogenetic status of SMV-R
      strongly supports a previous hypothesis that watermelon mosaic virus arose from a
      recombination event between SMV and a BCMV-like virus. 

PMID- 24445814
TI  - Epigenetics and memigenetics.
AB  - The field of epigenetics is expanding rapidly, yet there is persistent
      uncertainty in the definition of the term. The word was coined in the mid
      twentieth century as a descriptor of how intrinsic, yet largely unknown, forces
      act with genes to channel progenitor cells along pathways of differentiation.
      Near the end of the twentieth century, epigenetics was defined more specifically
      as the study of changes in gene activity states. In some definitions, only those
      activity states that are inherited across cell division were considered. Other
      definitions were broader, also including activity states that are transient, or
      occurring in non-dividing cells. The greatest point of disagreement in these
      current definitions, is if the term should concern only inherited activity
      states. To alleviate this disparity, an alternative term, 'memigenetics', could
      be used in place of epigenetics to describe inherited chromatin activity states.
      The advantage of this term is that it is self-defining, and would serve to
      emphasize the important concept of cell memory. It would also free the term
      epigenetics to be used in a broader sense in accord with the meaning of the
      prefix 'epi', that is, as a descriptor of what is 'over' DNA at any point in
      time. 

PMID- 24445815
TI  - Pathogenesis of skin ulcers: lessons from the Mycobacterium ulcerans and
      Leishmania spp. pathogens.
AB  - Skin ulcers are most commonly due to circulatory or metabolic disorders and are a
      major public health concern. In developed countries, chronic wounds affect more
      than 1 % of the population and their incidence is expected to follow those
      observed for diabetes and obesity. In tropical and subtropical countries, an
      additional issue is the occurrence of ulcers of infectious origins with diverse
      etiologies. While the severity of cutaneous Leishmaniasis correlates with
      protective immune responses, Buruli ulcers caused by Mycobacterium ulcerans
      develop in the absence of major inflammation. Based on these two examples, this
      review aims to demonstrate how studies on microorganism-provoked wounds can
      provide insight into the molecular mechanisms controlling skin integrity. We
      highlight the potential interest of a mouse model of non-inflammatory skin
      ulceration caused by intradermal injection of mycolactone, an original lipid
      toxin with ulcerative and immunosuppressive properties produced by M. ulcerans.

PMID- 24445816
TI  - Molecular cloning of Pcc-dmrt1s and their specific expression patterns in Pengze
      crucian carp (Carassius auratus var. Pengze) affected by 17alpha
      methyltestosterone.
AB  - Dmrt1, an important transcription factor associated with testicular
      differentiation, is conserved among teleost, which could also be detected in
      ovaries. In the present study, three isoforms of Pcc-dmrt1s (Pcc-dmrt1a, Pcc
      dmrt1b and Pcc-dmrt1c) resulting from alternative splicing of the dmrt1 gene were
      cloned and characterized in the triploid gynogenetic fish, the Pengze crucian
      carp. Their mRNA expression profiling was investigated in juvenile developmental
      stages, tissues of the adult fish, and the juveniles under 84.2 ng/L 17alpha
      methyltestosterone (MT) treatments. Results showed that their putative proteins
      shared high identities to Dmrt1 in cyprinid fish species. Gene expression
      profiling in the developmental stages showed that all the three target genes had
      a highest/lowest expression at 56/40 days post-hatching (dph), respectively. The
      period of 40 dph appeared to be a key time during the process of the ovary
      development of Pengze crucian carp. The tissue distribution results indicated
      that Pcc-dmrt1s were predominantly expressed in hepatopancreas, brain, spleen and
      ovary of the female fish. MT significantly increased the mRNA expression of Pcc
      dmrt1a (all 4-week exposures) and Pcc-dmrt1b (except for week 2), while repressed
      Pcc-dmrt1c transcripts at all exposure period except for week 2. MT extremely
      significant repressed cyp19a1a transcripts for 1 week. The present study
      indicated that MT could influence the ovary development of Pengze crucian carp by
      disturbing gene expressions of Pcc-dmrt1s and cyp19a1a. Furthermore, the present
      study will be of great significance to broaden the understanding of masculinizing
      pathway during ovary development in gynogenetic teleost. 

PMID- 24445819
TI  - Gynecologic cancers in pregnancy: guidelines of a second international consensus
      meeting.
AB  - OBJECTIVES: This study aimed to provide timely and effective guidance for
      pregnant women and health care providers to optimize maternal treatment and fetal
      protection and to promote effective management of the mother, fetus, and neonate
      when administering potentially teratogenic medications. New insights and more
      experience were gained since the first consensus meeting 5 years ago. METHODS:
      Members of the European Society of Gynecological Oncology task force "Cancer in
      Pregnancy" in concert with other international experts reviewed the existing
      literature on their respective areas of expertise. The summaries were
      subsequently merged into a complete article that served as a basis for discussion
      during the consensus meeting. All participants approved the final article.
      RESULTS: In the experts' view, cancer can be successfully treated during
      pregnancy in collaboration with a multidisciplinary team, optimizing maternal
      treatment while considering fetal safety. To maximize the maternal outcome,
      cancer treatment should follow a standard treatment protocol as for nonpregnant
      patients. Iatrogenic prematurity should be avoided. Individualization of
      treatment and effective psychologic support is imperative to provide throughout
      the pregnancy period. Diagnostic procedures, including staging examinations and
      imaging, such as magnetic resonance imaging and sonography, are preferable.
      Pelvic surgery, either open or laparoscopic, as part of a treatment protocol, may
      reveal beneficial outcomes and is preferably performed by experts. Most standard
      regimens of chemotherapy can be administered from 14 weeks gestational age
      onward. Apart from cervical and vulvar cancer, as well as important vulvar
      scarring, the mode of delivery is determined by the obstetrician. Term delivery
      is aimed for. Breast-feeding should be considered based on individual drug safety
      and neonatologist-breast-feeding expert's consult. CONCLUSIONS: Despite limited
      evidence-based information, cancer treatment during pregnancy can succeed. State
      of-the-art treatment should be provided for this vulnerable population to
      preserve maternal and fetal prognosis. SUPPLEMENTARY INFORMATION: Supplementary
      data on teratogenic effects, ionizing examinations, sentinel lymph node biopsy,
      tumor markers during pregnancy, as well as additional references and tables are
      available at the extended online version of this consensus article, go to
      http://links.lww.com/IGC/A197.

PMID- 24445820
TI  - Abdominal radical trachelectomy: a Romanian series.
AB  - OBJECTIVE: Abdominal radical trachelectomy (ART) is one of the fertility-sparing
      procedures in women with early-stage cervical cancer. The published results of
      ART, in comparison with vaginal radical trachelectomy, so far are limited.
      MATERIALS AND METHODS: This retrospective study comprises all cases of female
      patients referred to ART with early-stage cervical cancer from 2 gynecologic
      oncology centers in Romania. RESULTS: A total of 29 women were referred for ART,
      but subsequently, fertility could not be preserved in 3 of them. Eleven women had
      stage IA2 disease (42.3%), 14 (53.8%) women had stage IB1 disease, and 1 (3.8%)
      woman had stage IB2 disease. Histologic subtypes were 15 (57.6%) squamous, 8
      (30.7%) adenocarcinoma, and 3 (11.5%) adenosquamous. There were no major
      intraoperative complications in both hospitals. Early postoperative complications
      were mainly related to the type C parametrectomy-bladder dysfunction for more
      than 7 days (8 [30.7%] women) and prolonged constipation (6 [23.0%] women). Other
      complications consisted in symptomatic lymphocele in 2 (7.6%) patients, which
      were drained. Median follow-up time was 20 months (range, 4-43 months). Up to the
      present time, there has been 1 (3.8%) recurrence in our series. Most patients did
      not experience late postoperative complications. Three (11.5%) women are
      amenorrheic, and 1 (3.8%) woman developed a cervical stenosis. Of the 23 women
      who have normal menstruation and maintained their fertility, a total of 7 (30.4%)
      women have attempted pregnancy, and 3 (42.8%) of them achieved pregnancy
      spontaneously. These pregnancies ended in 2 first trimester miscarriages and 1
      live birth at term by cesarean delivery. CONCLUSIONS: Our results demonstrate
      that ART preserves fertility and maintains excellent oncological outcomes with
      low complication rates.

PMID- 24445817
TI  - PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX
      pathway.
AB  - Mixed lineage leukemia (MLL) fusion proteins directly activate the expression of
      key downstream genes such as MEIS1, HOXA9 to drive an aggressive form of human
      leukemia. However, it is still poorly understood what additional transcriptional
      regulators, independent of the MLL fusion pathway, contribute to the development
      of MLL leukemia. Here we show that the transcription factor PU.1 is essential for
      MLL leukemia and is required for the growth of MLL leukemic cells via the
      promotion of cell-cycle progression and inhibition of apoptosis. Importantly,
      PU.1 expression is not under the control of MLL fusion proteins. We further
      identified a PU.1-governed 15-gene signature, which contains key regulators in
      the MEIS-HOX program (MEIS1, PBX3, FLT3, and c-KIT). PU.1 directly binds to the
      genomic loci of its target genes in vivo, and is required to maintain active
      expression of those genes in both normal hematopoietic stem and progenitor cells
      and in MLL leukemia. Finally, the clinical significance of the identified PU.1
      signature was indicated by its ability to predict survival in acute myelogenous
      leukemia patients. Together, our findings demonstrate that PU.1 contributes to
      the development of MLL leukemia, partially via crosstalk with the MEIS/HOX
      pathway.

PMID- 24445821
TI  - Co-infection with Anaplasma platys, Bartonella henselae, Bartonella koehlerae and
      'Candidatus Mycoplasma haemominutum' in a cat diagnosed with splenic
      plasmacytosis and multiple myeloma.
AB  - Anaplasma platys (Apl), 'Candidatus Mycoplasma haemominutum' (CMh), Bartonella
      henselae (Bh) and Bartonella koehlerae (Bk) were confirmed by polymerase chain
      reaction (PCR) amplification and DNA sequencing in a cat diagnosed with multiple
      myeloma. Other inconsistently documented hematologic abnormalities included
      anemia, thrombocytopenia, eosinophilia and hypoglycemia. Persistent Apl infection
      was confirmed for the first time in a North American cat by sequencing three
      bacterial genes (16S rRNA, p44 and GroEL) in peripheral blood samples collected
      100 days apart. Following doxycycline treatment for Apl, multiple myeloma was
      diagnosed based upon a monoclonal gammopathy and splenic plasmacytosis, and the
      cat was treated with melphalan, chlorambucil and prednisolone. Apl DNA was not
      amplified from post-treatment blood samples and the hyperglobulinemia resolved
      temporarily following chemotherapy. Retrospective PCR analysis of stored DNA
      extracts identified CMh, Bk and Bh infections. Retrospective PCR for antigen
      receptor rearrangements (PARR) of splenic aspirates did not confirm B- or T-cell
      clonality. Co-infection with multiple vector-borne pathogens should be a
      diagnostic consideration in cats with chronic hypergammaglobulinemia, monoclonal
      gammopathy and splenic plasmacytosis. 

PMID- 24445822
TI  - Pediatric invasive Haemophilus influenzae infections in Israel in the era of
      Haemophilus influenzae type b vaccine: a nationwide prospective study.
AB  - BACKGROUND: The conjugated Haemophilus influenzae (Hi) type b vaccine caused a
      marked decrease in invasive Hi disease rates. Nonencapsulated Hi infection now
      constitutes most invasive Hi morbidity and mortality. This study examines
      invasive Hi infection incidence in Israel in the postvaccine era years, 2003
      2012, and characterizes the epidemiology, clinical diagnosis and case fatality
      rates of invasive Hi disease in children <15 years of age. METHODS: An ongoing,
      nationwide prospective surveillance program for invasive Hi infections in Israel.
      Epidemiologic and clinical data were collected. Diagnoses were classified as
      meningitis, pneumonia, bacteremia/sepsis and other clinical foci. RESULTS:
      Overall, 389 cases of invasive Hi infections were identified; 242 (62%)
      nontypable Hi (NTHi), 103 (26%) Hi type b (Hib) and 41 (11%) encapsulated non-b
      Hi (enbHi). Children <1 year of age accounted for 51% of the overall disease.
      Invasive Hi disease incidence in children <15 years of age was stable with a mean
      annual incidence (per 100,000) of 2.0 +/- 0.4. The highest incidence of invasive
      Hi infections was among infants <1 year with rates of 6.2, 4.9, 1.6 and 12.7 for
      NTHi, Hib, enbHi and total Hi, respectively. The clinical diagnoses of NTHi and
      enbHi were similar, but differed from Hib with the former presenting mostly as
      isolated sepsis/bacteremia and the latter primarily as meningitis. Among children
      with invasive Hib infection, 40% were classified as vaccine failure. CONCLUSIONS:
      In the post-Hib vaccination era, invasive Hi morbidity and mortality are largely
      attributed to NTHi sepsis. Still, with the changing epidemiology of invasive Hi,
      continued surveillance of all Hi strains is justified.

PMID- 24445823
TI  - Occurrence of 3 Bordetella species during an outbreak of cough illness in Ohio:
      epidemiology, clinical features, laboratory findings and antimicrobial
      susceptibility.
AB  - BACKGROUND: An increase in laboratory diagnosis of pertussis was noted in central
      Ohio during 2010. Diagnosis was made using a polymerase chain reaction assay
      targeting the multicopy insertion sequence IS481, which is found in both
      Bordetella pertussis (Bp) and Bordetella holmesii (Bh). An increase in specimens
      testing positive for Bordetella parapertussis (Bpp) using insertion sequence
      IS1001 was also noted. METHODS: Nasopharyngeal swab specimens submitted April 1,
      2010, to March 31, 2011, were tested using a multiplex polymerase chain reaction
      assay for Bp/Bh (IS481) and Bpp followed by singleplex assays for Bp and Bh. A
      subgroup of specimens was also cultured for Bordetella species, and antimicrobial
      susceptibility testing was performed on recovered organisms. Demographic and
      clinical features were compared for patients with Bp, Bh and Bpp. RESULTS: Of 520
      IS481-positive specimens, 214 (41.1%) were positive for Bp, 79 (15.2%) were
      positive for Bh and 5 (1.0%) were positive for both Bp and Bh; 222 (42.7%) were
      negative for both targets. An additional 220 specimens were positive for Bpp.
      Among a sample of 155 IS481-positive specimens, 40, 15 and 0 were culture
      positive for Bp, Bh and Bpp, respectively. Among a sample of 55 BparaIS1001
      positive (Bpp) specimens, 22, 0 and 0 were culture positive for Bpp, Bp and Bh,
      respectively. All Bordetella species were susceptible to macrolide antibiotics.
      Patients with Bh were older than patients with Bp, who were older than those
      positive for Bpp (mean ages: 12.0, 8.0 and 4.2 years, respectively; P < 0.001).
      One or more classic signs of pertussis (ie, paroxysmal cough, whoop, post-tussive
      emesis) were seen in 55.9% of 263 patients (59 Bp, 24 Bh, 80 Bpp and 100 negative
      for Bordetella species), but did not differ statistically among the groups (chi =
      5.1, P = 0.17). CONCLUSIONS: All 3 Bordetella species, Bp, Bh and Bpp, were
      detected during on outbreak of pertussis-like cough illness. There were noted
      differences in age and seasonality, but clinical features at the time of
      presentation did not allow clear differentiation of these infections. All
      Bordetella species recovered from culture and tested were susceptible in vitro to
      macrolide antibiotics. Additional study is necessary to further characterize
      epidemiologic and clinical characteristics of Bh-associated cough illness and to
      determine potential co-occurrence of Bordetella species with other bacterial and
      viral respiratory tract pathogens.

PMID- 24445824
TI  - Rhinoscleroma in a 5-year-old Portuguese Child.
AB  - Rhinoscleroma is a chronic granulomatous infectious disease that is rare in
      Western Europe. We report the case of a 5-year-old Portuguese boy diagnosed with
      rhinoscleroma in the context of recurrent epistaxis. He had a 6-month course of
      antibiotic (amoxicillin plus clavulanate) therapy with full recovery. 

PMID- 24445825
TI  - Chronic granulomatous disease presenting with salmonella brain abscesses.
AB  - Chronic granulomatous disease is a rare primary immunodeficiency caused by
      phagocytic cell defect. We describe the case of 43-month-old boy with chronic
      granulomatous disease presenting with Salmonella spp brain abscesses, together
      with a review of the 13 cases reported in the literature. 

PMID- 24445826
TI  - Sequential influenza B viral load and susceptibility in children treated with
      oseltamivir and zanamivir.
AB  - BACKGROUND: The objective of this study was to estimate the efficacy of the
      neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir for decreasing
      viral load and to investigate whether NAI treatment decreases viral
      susceptibility to NAIs over time in children with influenza B virus infection.
      METHODS: Of 27 patients with influenza B virus infection, 8 and 9 were treated
      with oseltamivir and zanamivir, respectively, whereas 10 received no NAI. Nasal
      aspiration samples, collected every morning until negative antigen results in 2
      consecutive samples were observed, were subjected to viral load measurements by
      quantitative real-time reverse transcription polymerase chain reaction and viral
      susceptibility to NAI by NA inhibition assays. RESULTS: Viral load decreased in
      both the oseltamivir and zanamivir groups by day 2 but increased in the no-NAI
      treatment group. Viral load in the oseltamivir and zanamivir groups on day 5 was
      2.6% and 9.2% of that on day 0, respectively, whereas it was 26.4% in the no-NAI
      treatment group. Mean 50% inhibitory concentration (IC50) values of oseltamivir
      and zanamivir in the no-NAI treatment group were 5.0-6.6 and 1.3-1.8 nM,
      respectively. Mean IC50 values of oseltamivir and zanamivir in patients treated
      with oseltamivir and zanamivir were 3.9-8.8 and 1.3-1.8 nM, respectively. No
      major decrease in viral susceptibility to NAIs was observed during or after NAI
      treatment. CONCLUSIONS: NAI treatment was effective for inhibiting viral
      replication during the early days of illness and did not decrease viral
      susceptibility to NAIs in patients with influenza B virus infection.

PMID- 24445827
TI  - Changes in childhood pneumonia and infant mortality rates following introduction
      of the 13-valent pneumococcal conjugate vaccine in Nicaragua.
AB  - BACKGROUND: In 2010, Nicaragua became the first developing nation to add 13
      valent pneumococcal conjugate vaccine (PCV-13) to its national immunization
      schedule, using a "3+0" dosing schedule. We assessed changes in incidence rates
      of health facility visits for childhood pneumonia and infant mortality after PCV
      13 introduction in the Department of Leon, Nicaragua. METHODS: We collected visit
      diagnoses from all 107 public health facilities in Leon between 2008 and 2012. We
      compared rates of pneumonia hospitalizations, ambulatory visits for pneumonia and
      infant mortality during the prevaccine (2008-2010) and vaccine (2011-2012)
      periods among different age groups of children using generalized estimating
      equations, accounting for clustering by municipality. Exposure time was estimated
      by official municipality population estimates. RESULTS: The adjusted incidence
      rate ratio for pneumonia hospitalization in the vaccine versus prevaccine period
      was 0.67 (0.59-0.75) among infants and 0.74 (0.67-0.81) among 1-year olds. The
      adjusted incidence rate ratio for ambulatory visits for pneumonia was 0.87 (0.75
      1.01) among infants, and 0.84 (0.74, 0.95) among 1-year olds. The adjusted
      incidence rate ratio for infant mortality was 0.67 (0.57-0.80). We also observed
      lower rates of health facility visits for pneumonia among age groups (2- to 4
      year old and 5- to 14-year old) not eligible to receive PCV-13. CONCLUSIONS:
      Within the first 2 years of a PCV-13 immunization program in Nicaragua, we
      observed lower rates of hospitalizations and ambulatory visits for pneumonia
      among children of all ages and a lower infant mortality rate. Lower rates of
      pneumonia among age groups not eligible to receive PCV-13 suggest an indirect
      effect of the vaccine.

PMID- 24445828
TI  - Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital
      toxoplasmosis.
AB  - BACKGROUND: Congenital toxoplasmosis can result in visual impairment, hearing
      loss, serious neurologic sequelae and death in the infant. We studied the
      potential of the polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) for
      diagnosis of congenital toxoplasmosis. METHODS: For this purpose, we studied both
      congenitally infected (diagnosed clinically and serologically) and noninfected
      infants born to untreated mothers. RESULTS: The infants ranged in age from 0 to
      180 days. CSF PCR was positive in 27 of the 58 (46.5%) congenitally infected
      infants and was negative in each of the 103 infants without congenital
      toxoplasmosis. The frequency of positive CSF PCR varied according to whether
      infants had major clinical signs of the disease; PCR was positive in 70.9%, 53.3%
      and 50.9% of those with hydrocephalus, cerebral calcifications and/or eye
      disease, respectively. Of 6 infants who were negative for both IgM and IgA
      antibodies, 3 had a positive PCR in their CSF as the confirmatory test for
      diagnosis of congenital toxoplasmosis. IgM and IgA antibodies and CSF PCR, when
      combined, yielded a higher sensitivity for diagnosis of congenital toxoplasmosis
      when compared with the performance of each test alone. CONCLUSIONS: Our findings
      reveal that in infants with clinical and serologic findings suggestive of
      congenital toxoplasmosis and born to untreated mothers, CSF PCR has the potential
      to increase the frequency of cases in which the diagnosis is confirmed.

PMID- 24445829
TI  - First trimester exposure to antiretroviral therapy and risk of birth defects.
AB  - BACKGROUND: Use of antiretroviral (ARV) drugs during pregnancy has been
      associated with an increased risk of birth defects, but the evidence remains
      inconclusive. METHODS: We identified infants born to human immunodeficiency virus
      (HIV)-infected mothers between 1994 and 2009 using Tennessee Medicaid data linked
      to vital records. Maternal HIV status was based on diagnosis codes, prescriptions
      for ARVs and HIV-related laboratory testing. ARV exposure was identified from
      pharmacy claims. Birth defects diagnoses during the first year of life were
      identified from maternal and infant claims and vital records and were confirmed
      through medical record review. Multivariate logistic regression models were used
      to evaluate associations between first trimester ARV dispensing and birth
      defects. RESULTS: Of 806 infants included in the study, 32 (4.0%) had at least 1
      major birth defect, most (44%) in the cardiac system. There was no increased risk
      for infants exposed in the first trimester to ARVs compared with unexposed
      infants (odds ratio = 1.07; 95% confidence interval: 0.50-2.31). Of the 20
      infants exposed to efavirenz, none had a birth defect (0%; 95% confidence
      interval: 0.0-13.2). CONCLUSIONS: There was no significant association between
      first trimester ARV dispensing and the risk of birth defects in this Medicaid
      cohort of HIV-positive women.

PMID- 24445830
TI  - Clinical evaluation of vancomycin dosage in pediatric oncology patients.
AB  - Vancomycin trough serum concentrations were below therapeutic range (8-15 mg/L)
      in 58% of 124 pediatric oncology patients receiving 60 mg/kg/d divided qid.
      Patients <6 and between 6 and 12 years had significantly lower trough
      concentrations than patients >12 years. A vancomycin dosage of 60 mg/kg/d is
      inadequate for pediatric oncology patients >12 years. 

PMID- 24445831
TI  - Predictive value of cerebrospinal fluid matrix metalloproteinase-9 and tissue
      inhibitor of metalloproteinase-1 concentrations in childhood bacterial
      meningitis.
AB  - BACKGROUND: Increased concentrations of matrix metalloproteinases (MMP) in
      cerebrospinal fluid are part of the host response in bacterial meningitis (BM).
      We investigated whether the concentrations of MMP-9 and the tissue inhibitor of
      metalloproteinase (TIMP)-1 predict the outcome in childhood BM. METHODS:
      Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      were quantified by an enzyme-linked immunosorbent assay from 264 and 335
      patients, respectively; 43 children without BM served as controls. The results
      were compared with previously known independent predictors of death and sequelae.
      RESULTS: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM
      patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent
      predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09
      7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma
      Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP
      1 levels correlated with the severity of sequelae (rho: 0.30; P < 0.0001), but
      not with death. Its concentration above 390 ng/mL increased the likelihood of
      sequelae 3.43-fold (95% CI: 1.73-6.79; P = 0.0004), and up to 31.18-fold (95% CI:
      4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12.
      CONCLUSIONS: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2
      important outcomes in childhood BM. Combined with a clinical evaluation,
      quantification of these indices augments the chances to identify the patients in
      greatest need of better treatment modalities.

PMID- 24445832
TI  - Quality of life after surgery for recurrent otitis media in a randomized
      controlled trial.
AB  - BACKGROUND: Tympanostomy with or without adenoidectomy is effective in preventing
      recurrences of acute otitis media (RAOM), but little is known about the effect of
      these operations on the quality of life (QOL). We evaluated the efficacy of
      insertion of tympanostomy tubes with and without adenoidectomy for improving QOL
      in young children in a controlled, randomized trial. METHODS: QOL was evaluated
      in the 159 children aged 10 months to 2 years participating in our larger study
      in which children with RAOM were randomly assigned to receive tympanostomy tubes,
      tympanostomy tubes with adenoidectomy or neither. The caregiver of the child
      completed otitis media-specific QOL questionnaires (Otitis Media-6) at entry and
      after 4 months and 12 months of follow up. RESULTS: Scores on the global ear
      related QOL and the subsets of caregiver concern, emotional distress and physical
      suffering in the questionnaires improved with time during the follow up, but the
      groups did not differ from each other. CONCLUSIONS: QOL in children with RAOM
      improves with time when the subjects are closely followed. Tympanostomy with
      adenoidectomy does not provide any additional QOL benefit for children with RAOM,
      even though these operations are effective in preventing further otitis media
      episodes.

PMID- 24445833
TI  - Safety and immunogenicity of an inactivated quadrivalent influenza vaccine in
      children 6 months through 8 years of age.
AB  - BACKGROUND: Strains of 2 distinct influenza B lineages (Victoria and Yamagata)
      have cocirculated in the United States for over a decade, but trivalent influenza
      vaccines (TIVs) contain only 1 B-lineage strain. Each season, some or most
      influenza B disease is caused by the B lineage not represented in that season's
      TIV. Quadrivalent influenza vaccines (QIVs) containing a strain from each B
      lineage should resolve this problem. METHODS: This was a Phase III, randomized,
      multicenter trial in the United States among children 6 months to <9 years of age
      to evaluate the safety and immunogenicity of inactivated QIV compared with
      inactivated control TIVs containing opposite B-lineage strains. Participants were
      randomized at a ratio of approximately 4:1:1 to receive QIV, TIV containing a
      Victoria-lineage B strain or TIV containing a Yamagata-lineage B strain. Sera
      were collected pre- and 28-days post-final vaccination and safety was assessed
      for 6 months after the last injection. RESULTS: A total of 4363 participants were
      enrolled. QIV induced noninferior antibody responses to all A strains and
      corresponding B strains compared with the control TIVs and superior antibody
      responses to the noncorresponding B strain in each TIV. Rates of solicited
      reactions and unsolicited and serious adverse events were similar in all groups.
      CONCLUSIONS: This study demonstrated that QIV is safe and immunogenic among
      children 6 months to <9 years of age. These findings, along with data from 2
      other studies of this QIV in adults, suggest that QIV should offer protection
      against both B lineages with a safety profile similar to TIV across all ages.

PMID- 24445834
TI  - The association of genetic variants in toll-like receptor 2 subfamily with
      allergy and asthma after hospitalization for bronchiolitis in infancy.
AB  - BACKGROUND: Toll-like receptors (TLRs) are a pivotal part of the innate immunity
      system. Variations in TLR genes have been connected to autoimmune conditions,
      such as allergy and asthma. The TLR2 subfamily comprises TLR1, TLR2, TLR6 and TLR
      10. We hypothesized that polymorphism of the TLR2 subfamily may be associated
      with prevalence of post-bronchiolitic asthma and/or atopy. METHODS:
      TLR1rs5743618, TLR2rs5743708 and TLR6rs5743810 single nucleotide polymorphisms of
      133 children who had been hospitalized for bronchiolitis at <6 months of age were
      analyzed. Doctor-diagnosed asthma and atopy as well as their occurrence during
      the first 6 years of life were evaluated during a follow-up visit. RESULTS: At
      the mean age of 6.4 years, asthma was present in 17 (13%) patients, there was
      asthma diagnosis during the first 6 years of life in 39 (29%) and current doctor
      diagnosed allergic rhinitis in 57 (43%) patients. Twenty-four (24%) children with
      G/G genotype in TLR1 rs5743618 were diagnosed to have asthma between 1 and 6
      years of age (vs. 13 (38%) of those with G/T or T/T genotypes; P = 0.04). In
      addition, 11/60 (18%) children with TLR6 rs5743810 C/T versus 36/73 (49%)
      children of other genotypes had atopic eczema at follow up. Only 2 children (8%)
      with wild genotype in all investigated single nucleotide polymorphisms had asthma
      during the first 6 years of life (vs. 30% in those with variant genotype of TLR1,
      TLR2 and/or TLR6). CONCLUSION: In this study, we demonstrated that TLR1 rs5743618
      was associated with asthma and atopic eczema during the first 6 years of life
      after early bronchiolitis. In addition, TLR6 rs5743810 was associated with
      present atopy at preschool age.

PMID- 24445835
TI  - Respiratory syncytial virus surveillance in the United States, 2007-2012: results
      from a national surveillance system.
AB  - BACKGROUND: Annual respiratory syncytial virus (RSV) outbreaks throughout the US
      exhibit variable patterns in onset, peak month of activity and duration of
      season. RSVAlert, a US surveillance system, collects and characterizes RSV test
      data at national, regional, state and local levels. METHODS: RSV test data from
      296 to 666 laboratories from 50 states, the District of Columbia and Puerto Rico
      (as of 2010) were collected during the 2007-2008 to 2011-2012 RSV seasons. Data
      were collected in early August/September to the following August/September each
      season. Participating laboratories provided the total number and types of RSV
      tests performed each week and test results. RSV season onset and offset were
      defined as the first and last, respectively, of 2 consecutive weeks during which
      the mean percentage of specimens testing positive for RSV was >=10%. RESULTS:
      Nationally, the RSV season onset occurred in October/November of each year with
      offset occurring in March/April of the following year. The RSV season averaged 20
      weeks and typically occurred earliest in the South and latest in the West. The
      onset, offset and duration varied considerably within the U.S. Department of
      Health and Human Services regions. RSV activity in Puerto Rico was elevated
      throughout the 2-year period studied. Median onset in core-based statistical
      areas ranged from 2 weeks earlier to 5 weeks later than those in their
      corresponding states. CONCLUSIONS: Substantial variability existed in the timing
      of RSV activity at all geographic strata analyzed. RSV actively circulated (ie,
      >=10%) in many areas outside the traditionally defined RSV epidemic period of
      November to March.

PMID- 24445836
TI  - Association between pulmonary ureaplasma colonization and bronchopulmonary
      dysplasia in preterm infants: updated systematic review and meta-analysis.
AB  - BACKGROUND: Previous meta-analyses have reported a significant association
      between pulmonary colonization with Ureaplasma and development of
      bronchopulmonary dysplasia (BPD). However, because few studies reporting oxygen
      dependency at 36 weeks corrected gestation were previously available, we updated
      the systematic review and meta-analyses to evaluate the association between
      presence of pulmonary Ureaplasma and development of BPD. METHODS: Five databases
      were searched for articles reporting the incidence of BPD at 36 weeks
      postmenstrual age (BPD36) and/or BPD at 28 days of life (BPD28) in Ureaplasma
      colonized and noncolonized groups. Pooled estimates were produced using random
      effects meta-analysis. Meta-regression was used to assess the influence of
      difference in gestational age between the Ureaplasma-positive and Ureaplasma
      negative groups. The effects of potential sources of heterogeneity were also
      investigated. RESULTS: Of 39 studies included, 8 reported BPD36, 22 reported
      BPD28 and 9 reported both. The quality of studies was assessed as moderate to
      good. There was a significant association between Ureaplasma and development of
      BPD36 (odds ratio = 2.22; 95% confidence intervals: 1.42-3.47) and BPD28 (odds
      ratio = 3.04; 95% confidence intervals: 2.41-3.83). Sample size influenced the
      odds ratio, but no significant association was noted between BPD28 rates and
      difference in gestational age between Ureaplasma colonized and noncolonized
      infants (P = 0.96). CONCLUSIONS: Pulmonary colonization with Ureaplasma continues
      to be significantly associated with development of BPD in preterm infants at both
      36 weeks postmenstrual age and at 28 days of life. This association at BPD28
      persists regardless of difference in gestational age.

PMID- 24445837
TI  - Management of latent tuberculosis infection in child contacts of multidrug
      resistant tuberculosis.
AB  - After exposure to a teacher with multidrug-resistant pulmonary tuberculosis, 31
      children developed latent infection. Twenty-six were treated with levofloxacin
      and pyrazinamide. Twelve required a change in therapy secondary to adverse
      effects. The most common adverse effects included abdominal pain,
      arthralgias/myalgias and elevated transaminases. All children reported at least 1
      adverse effect. Fifteen children completed treatment. All adverse effects were
      transient. 

PMID- 24445838
TI  - The effect of birth month on the risk of respiratory syncytial virus
      hospitalization in the first year of life in the United States.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of severe
      respiratory illness in infants. To help direct targeted interventions and future
      RSV vaccine programs, we examined risk of RSV-related hospitalization by infant
      age and birth month. METHODS: We conducted Poisson regression analyses to
      evaluate birth month as a risk factor for RSV-related pediatric hospitalizations
      (identified by any mention of ICD-9-CM diagnosis codes: 466.11, 480.1 or 079.6)
      from State Inpatient Data in Arizona, Iowa, New York, Oregon and Wisconsin
      between July 1996 and June 2006. We used an age cohort approach to compute total
      relative risk of RSV during the first year of life. RESULTS: We identified 82,296
      RSV-related infant hospital admissions, corresponding to 13.9 per 1000 person
      years among infants <12 months of age. Of these, 42% of the patients were female
      and 73% were <6 months old. One-month-old infants born in January were ~10 times
      more at risk for RSV-related hospitalization than 1-month-old infants born in
      October [relative risk: 9.8 (7.8-12.4)]. Across the first year of life, infants
      born in December and January had a 2- and 3-fold higher risk, respectively, of an
      RSV-related hospitalization event than infants born in July. CONCLUSIONS: Birth
      month and age at admission impacted the risk of RSV-related hospitalization
      within the first year of life in 5 states we investigated. As RSV vaccine
      candidates are currently under investigation in clinical trials, our findings
      help identify ideal RSV vaccine schedules to prevent early and severe events
      while improving the use of expensive prophylactic drugs.

PMID- 24445839
TI  - Antibody and cell-mediated immunity to pertussis 4 years after monovalent
      acellular pertussis vaccine at birth.
AB  - BACKGROUND: In a previous study, we found that monovalent acellular pertussis
      (aP) vaccine at birth and 1 month achieves higher IgG antibody (Ab) levels to
      pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin by 8 weeks,
      when compared with controls. Here, we report antibody and cell-mediated immune
      responses to 4 years of age. METHODS: IgG Ab to PT, filamentous hemagglutinin and
      pertactin, diphtheria (D) and tetanus (T) was measured in the 3 groups (aP
      vaccine at birth and 1 month, aP birth only and no aP) at 2 years of age and
      before and after DTaP-inactivated polio vaccine (DTaP-IPV) at 4 years of age.
      Cell-mediated immune responses to pertussis vaccine antigens were measured at 2
      years of age. Adverse events following DTaP-IPV were recorded. RESULTS: Of 74
      subjects, 52 (70%) were available for follow up. Overall, 11 (21%) had detectable
      PT IgG at 2 years, decreasing to 10% before 4-year-old booster compared with 100%
      at 8 months of age. After the 4-year booster, pertussis antigen IgG levels were
      similar, but there was a trend to lower PT IgG levels in birth aP infants
      (geometric mean concentrations: 28.7 EI.U/mL) compared with controls (geometric
      mean concentrations: 53.6 EI.U/mL). The cytokine responses to pertussis antigen
      stimulation were higher in aP recipients at 2 years of age. There was no
      difference in injection site reactions among groups following the DTaP-IPV
      booster at 4 years of age. CONCLUSIONS: In the longest reported follow-up of
      infants who received aP vaccine at birth, we found a trend to lower PT IgG
      antibodies post booster compared with receipt of first dose of aP-containing
      vaccine at 8 weeks of age. Short- and long-term antibody responses with and
      without prior maternal pertussis vaccination are crucial for further evaluation
      of this strategy for preventing severe early pertussis.

PMID- 24445840
TI  - Thermotropic phase boundaries in classic ferroelectrics.
AB  - High-performance piezoelectrics are lead-based solid solutions that exhibit a so
      called morphotropic phase boundary, which separates two competing phases as a
      function of chemical composition; as a consequence, an intermediate low-symmetry
      phase with a strong piezoelectric effect arises. In search for environmentally
      sustainable lead-free alternatives that exhibit analogous characteristics, we use
      a network of competing domains to create similar conditions across thermal inter
      ferroelectric transitions in simple, lead-free ferroelectrics such as BaTiO3 and
      KNbO3. Here we report the experimental observation of thermotropic phase
      boundaries in these classic ferroelectrics, through direct imaging of low
      symmetry intermediate phases that exhibit large enhancements in the existing
      nonlinear optical and piezoelectric property coefficients. Furthermore, the
      symmetry lowering in these phases allows for new property coefficients that
      exceed all the existing coefficients in both parent phases. Discovering the
      thermotropic nature of thermal phase transitions in simple ferroelectrics thus
      presents unique opportunities for the design of 'green' high-performance
      materials. 

PMID- 24445841
TI  - Kinetically controlled phenomena in dynamic combinatorial libraries.
AB  - Dynamic combinatorial libraries (DCLs) are collections of structurally related
      compounds that can interconvert through reversible chemical reaction(s). Such
      reversibility endows DCLs with adaptability to external stimuli, as rapid
      interconversion allows quick expression of those DCL components which best
      respond to the disturbing stimulus. This Tutorial Review focuses on the
      kinetically controlled phenomena that occur within DCLs. Specifically, it will
      describe dynamic chiral resolution of DCLs, their self-sorting under the
      influence of irreversible chemical and physical stimuli, and the autocatalytic
      behaviours within DCLs which can result in self-replicating systems. A brief
      discussion of precipitation-induced phenomena will follow and the review will
      conclude with the presentation of covalent organic frameworks (COFs)-porous
      materials whose synthesis critically depends on the fine tuning of the crystal
      growth and error correction rates within large DCLs. 

PMID- 24445842
TI  - Variation in cyanobacterial hepatotoxin (microcystin) content of water samples
      and two species of fishes collected from a shallow lake in Algeria.
AB  - Microcystins (MCs) produced from cyanobacteria can accumulate in freshwater fish
      tissues. In this study, variations in these toxins content were examined monthly
      in water samples and two species of fish in Lake Oubeira, Algeria, from April
      2010 to March 2011. During the study period, MCs were analyzed using protein
      phosphatase type 2A (PP2A) inhibition assay. In lake water, total (dissolved and
      intracellular toxins) MC concentrations by PP2A ranged from 0.028 to 13.4 MUg
      equivalent MC-LR/l, with a peak in September 2010. MC-LR was the dominant variant
      (90 % of the total) in water samples, followed by MC-YR and MC-(H4)YR. The
      highest MC concentration in the omnivorous common carp (Cyprinus carpio) was
      found in the order intestine > hepatopancreas > muscle; however, in the
      carnivorous European eel (Anguilla anguilla) the order was liver > intestine >
      muscle. Highest MC concentrations in the intestine tissue of the common carp were
      found between August and November 2010 where high MC concentrations were detected
      in water samples, whereas high levels of MCs in the liver of the European eel
      were found later between January and February 2011. During the entire period of
      study, the World Health Organization (WHO) lifetime limit for tolerable daily
      intake was exceeded only in common carp muscle. 

PMID- 24445844
TI  - Anatomical aberrations in root canals of maxillary first and second molar teeth:
      an endodontic challenge.
AB  - Root canal anatomy variations present a constant challenge in successful
      diagnosis and endodontic treatment, especially the multirooted teeth. Maxillary
      first molar is the most commonly treated tooth yet with frequent failures because
      of undetected canals, especially the mesiobuccal second canal (MB2) with more
      frequency and distobuccal second canal (DB2) with quite a less frequency. Also,
      there are limited chances to find MB2 in maxillary second molars. We present two
      such cases, each of maxillary first and second molar with extra distobuccal and
      mesiobuccal canals, respectively. 

PMID- 24445845
TI  - Type I aortopulmonary window presenting with very early onset Eisenmenger's
      syndrome.

PMID- 24445843
TI  - Perturbation of mitiglinide metabolism by chronic unpredicted mild stress in
      rats.
AB  - Many diabetic patients complicated with wild to severe depression. It is unclear
      in diabetic medication whether depression perturbs the drug metabolic process of
      the hypoglycemic agents or not. The present study was designed to investigate the
      impact of chronic unpredicted mild stress (CUMS) -induced depression on
      mitiglinide (MGN) pharmacokinetics in rats. Adult female Sprague-Dawley rats in
      CUMS group were subjected to different types of stressors and the stress
      procedures lasted for 8 weeks. Control group without receiving stress had free
      access to food and water. Open-field test and 5-HT levels were assayed to
      evaluate the depression. After CUMS all rats were given 2.5 mg/kg of mitiglinide
      per os. The blood samples were collected at different time and mitiglinide plasma
      concentration was measured by high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS). Non-compartmental statistical moment analysis was
      processed with DAS software. In CMUS-induced depression group, peak concentration
      (Cmax), peak time (Tmax), area under curve (AUC0 -> infinity), mean residence
      time (MRT0 -> infinity), and half-life (T1/2z) were reduced while total plasma
      clearance (CLz/F) was increased compared to control group. These preliminary
      results indicated that CUMS-induced depression alter the drug metabolic process
      of mitiglinide in rats. This finding will be significant in clinic. 

PMID- 24445846
TI  - Non-traumatic, bilateral subcapital femoral fractures postpartum.
AB  - A 28-year-old Romanian woman, presented 2 weeks postnatally with pain in her left
      hip. Plain radiography suggested a left intracapsular, subcapital hip fracture. A
      CT scan of the pelvis showed diffuse osteopaenia with bilateral subcapital
      fractures of both femurs. From this imaging and subsequent investigation, a
      diagnosis of transient osteoporosis of pregnancy was made. The patient was
      treated with a closed reduction and cannulated screw fixation. Rehabilitative
      treatment, vitamin D, calcium and bisphosphonate therapy were initiated. She
      remains under close follow-up from orthopaedic, rheumatological and endocrine
      teams. Multiple opportunities were missed to identify the source of the patient's
      pain and inability to weight bear. Early detection and management of this
      condition is crucial because of the associated morbidity, including debilitating
      pain, reduced mobility, fractures and avascular necrosis. Cessation of
      breastfeeding, adequate pain relief, early use of bisphosphonates and
      rehabilitative treatment are essential. 

PMID- 24445847
TI  - Unilateral iatrogenic ptosis.

PMID- 24445848
TI  - Left renal vein thrombosis: a rare cause of acute scrotal pain.

PMID- 24445849
TI  - Surgical therapy of a large pancreatic solid-pseudopapillary neoplasm during
      pregnancy.
AB  - Solid-pseudopapillary neoplasms (SPNs) of the exocrine pancreas are rare,
      accounting for only 2% of pancreatic tumours. These tumours predominantly affect
      women during the second and third decades of life. They frequently present with
      vague symptoms and can pose a diagnostic challenge. Surgical resection remains
      the treatment of choice that can cure up to 95% of patients when negative
      resection margins are obtained. SPNs diagnosed during pregnancy are exceptional
      and with profound implications on the mother and fetus. The authors present a
      case of an asymptomatic SPN in a 24-year-old woman diagnosed at 14 weeks of
      gestation on a routine prenatal ultrasound. Distal pancreatectomy, splenectomy
      and cholecystectomy were successfully performed at 18 weeks of gestation. A
      healthy full-term male child was born 5 months following surgery without
      complications. 

PMID- 24445850
TI  - Resolution of neurological deficits secondary to spontaneous intracranial
      haemorrhage and posterior reversible encephalopathy syndrome (PRES) in a patient
      with hepatitis C-associated cryoglobulinaemia: a role for plasmapheresis.
AB  - Essential mixed cryoglobulinaemia or type II cryoglobulinaemia is an important
      extrahepatic manifestation of chronic hepatitis C. Cryoglobulinaemia results in
      the deposition of immune complexes in small or medium-sized blood vessels leading
      to palpable purpura, arthralgia, renal disease and peripheral neuropathy.
      Posterior reversible encephalopathy syndrome (PRES) is a distinct phenomenon
      characterised by vasogenic oedema in the posterior circulation of brain.
      Cryoglobulinaemic vasculitis leading to spontaneous intracranial haemorrhage and
      PRES syndrome is rarely reported in the medical literature. In this report, we
      present an unusual case of spontaneous intracranial haemorrhage and PRES
      secondary to hepatitis C-associated cryoglobulinaemia presenting as right dense
      hemiplegia. Prompt institution of plasmapheresis resulted in successful
      resolution of symptoms in our patient, followed by full neurological recovery. To
      the best of our knowledge, this case describes the first successful use of
      plasmapheresis in alleviating neurological complications resulting from
      cryoglobulinaemic vasculitis and PRES secondary to chronic hepatitis C. 

PMID- 24445851
TI  - Lung abscess in a young patient.

PMID- 24445852
TI  - Congenital asymptomatic absence of unilateral sternocleidomastoid muscle.

PMID- 24445853
TI  - Inferolateral ST-segment elevation associated with a gastric variceal bleed and
      the use of a Minnesota tube.
AB  - The use of Minnesota and modified Sengstaken-Blakemore tubes for balloon
      tamponade in acute variceal haemorrhage has declined with the availability of
      modern endoscopic techniques. However, in massive uncontrolled haemorrhage their
      use may still be required. They are very effective in controlling acute bleeding,
      but are associated with a range of potentially serious complications. This case
      demonstrates an unusual complication of the use of a Minnesota tube in a
      gentleman with a large gastric variceal bleed. The patient developed
      inferolateral ST-segment elevation on a 12-lead ECG which resolved rapidly
      following aspiration of 2000 mL of blood from the gastric port of the Minnesota
      tube. It was thought that the distension of the stomach, along with the traction
      applied to the Minnesota tube, resulted in external compression of the
      diaphragmatic surface of the heart and the observed ECG changes. 

PMID- 24445854
TI  - Extensive disseminated cysticercosis.

PMID- 24445855
TI  - Gastric epithelioid-cell granuloma in a paediatric patient with Crohn's disease.

PMID- 24445856
TI  - Effect of farm management practices in the Bt toxin production by Bt cotton:
      evidence from farm fields in China.
AB  - Based on farm field plot level survey data and laboratory test, we examine the
      determinants of the expression of Bt toxin in China's Bt cotton production. The
      results show that the expression of Bt toxin differs significantly among
      varieties. Even for the same variety the expression of Bt toxin also varies
      substantially among villages and among farmers in the same village. Econometric
      analyses show that after controlling for the effects of varieties and locations
      (or villages), farm management, particular applications of phosphate and potash
      fertilizers, and manure, has significant positive effects on Bt toxin expression
      in farmer's fields. In contrast to previous studies which showed that nitrogen
      fertilizer has a positive impact on expression of Bt toxin, this study shows that
      nitrogen fertilizer has no significant impact on expression of Bt toxin in
      farmer's fields. On the other hand, the expression of Bt toxin has a positive
      relationship with phosphate fertilizer, potash fertilizer and manure application.

PMID- 24445857
TI  - NICE to set out how it will judge social benefits of drugs.

PMID- 24445858
TI  - Genetic association of IL-21 polymorphisms with dilated cardiomyopathy in a Han
      Chinese population.
AB  - BACKGROUND: Autoimmune abnormalities appear to be major predisposing factors for
      dilated cardiomyopathy (DCM). Interleukin-21 (IL-21) gene polymorphisms have been
      previously found to be associated with autoimmune diseases. This study aimed to
      assess the role of IL-21 in DCM in a Han Chinese population. PATIENTS AND
      METHODS: A total of 364 independent DCM patients and 384 unrelated healthy
      controls were recruited for this case-control association study. rs2055979 and
      rs12508721 were genotyped by PCR-RFLP. IL-21 plasma levels in samples from DCM
      and control individuals were evaluated by ELISA. The association between the SNPs
      and overall survival (OS) was evaluated by Kaplan-Meier analysis. Hazard ratios
      and 95 % confidence intervals (CIs) were assessed in a Cox regression analysis
      with adjustment for sex and age. RESULTS: The T allele frequencies of both SNPs
      were higher in DCM patients than in controls (p < 0.001). The genotypic
      frequencies of rs2055979 G > T and rs12508721 C > T were associated with DCM in
      the codominant, dominant, and recessive models (p < 0.05). IL-21 plasma levels in
      patients were higher than those of the control subjects (p = 0.009). The TT
      genotypes of both SNPs were associated with significantly higher plasma levels
      (prs2055979 = 0.03, prs12508721 < 0.001). Kaplan-Meier analysis showed that the
      genotypic frequencies of both SNPs were associated with OS in the dominant and
      the recessive models (p < 0.001). The TT genotypes of both SNPs were associated
      with the worst OS (p < 0.001). CONCLUSION: Our findings suggest that theIL-21
      gene plays an important role in susceptibility to DCM as well as in the clinical
      outcome of this ailment in the Han Chinese population.

PMID- 24445859
TI  - A high-energy-density sugar biobattery based on a synthetic enzymatic pathway.
AB  - High-energy-density, green, safe batteries are highly desirable for meeting the
      rapidly growing needs of portable electronics. The incomplete oxidation of sugars
      mediated by one or a few enzymes in enzymatic fuel cells suffers from low energy
      densities and slow reaction rates. Here we show that nearly 24 electrons per
      glucose unit of maltodextrin can be produced through a synthetic catabolic
      pathway that comprises 13 enzymes in an air-breathing enzymatic fuel cell. This
      enzymatic fuel cell is based on non-immobilized enzymes that exhibit a maximum
      power output of 0.8 mW cm(-2) and a maximum current density of 6 mA cm(-2), which
      are far higher than the values for systems based on immobilized enzymes.
      Enzymatic fuel cells containing a 15% (wt/v) maltodextrin solution have an energy
      storage density of 596 Ah kg(-1), which is one order of magnitude higher than
      that of lithium-ion batteries. Sugar-powered biobatteries could serve as next
      generation green power sources, particularly for portable electronics.

PMID- 24445860
TI  - A direct, versatile route to functionalized trialkoxysilanes.
AB  - The peroxide initiated radical addition of dithiocarbonates (xanthates) to
      trialkoxy vinylsilanes leads to functionalized trialkoxysilanes. Prior addition
      of the dithiocarbonates to an alkene before reaction with the vinylsilane can be
      used to increase the complexity of the final product. 

PMID- 24445861
TI  - Public health practice course using Google Plus.
AB  - In recent years, mobile device-assisted clinical education has become popular
      among nursing school students. The introduction of mobile devices saves manpower
      and reduces errors while enhancing nursing students' professional knowledge and
      skills. To respond to the demands of various learning strategies and to maintain
      existing systems of education, the concept of Cloud Learning is gradually being
      introduced to instructional environments. Cloud computing facilitates learning
      that is personalized, diverse, and virtual. This study involved assessing the
      advantages of mobile devices and Cloud Learning in a public health practice
      course, in which Google+ was used as the learning platform, integrating various
      application tools. Users could save and access data by using any wireless
      Internet device. The platform was student centered and based on resource sharing
      and collaborative learning. With the assistance of highly flexible and convenient
      technology, certain obstacles in traditional practice training can be resolved.
      Our findings showed that the students who adopted Google+ were learned more
      effectively compared with those who were limited to traditional learning systems.
      Most students and the nurse educator expressed a positive attitude toward and
      were satisfied with the innovative learning method. 

PMID- 24445862
TI  - Osteoporosis: Novel antibody therapy shows potential for building bone.

PMID- 24445863
TI  - Validity and reliability of the Nintendo Wii Balance Board to assess standing
      balance and sensory integration in highly functional older adults.
AB  - Standing balance is an important motor task. Postural instability associated with
      age typically arises from deterioration of peripheral sensory systems. The
      modified Clinical Test of Sensory Integration for Balance and the Tandem test
      have been used to screen for balance. Timed tests present some limitations,
      whereas quantification of the motions of the center of pressure (CoP) with
      portable and inexpensive equipment may help to improve the sensitivity of these
      tests and give the possibility of widespread use. This study determines the
      validity and reliability of the Wii Balance Board (Wii BB) to quantify CoP
      motions during the mentioned tests. Thirty-seven older adults completed three
      repetitions of five balance conditions: eyes open, eyes closed, eyes open on a
      compliant surface, eyes closed on a compliant surface, and tandem stance, all
      performed on a force plate and a Wii BB simultaneously. Twenty participants
      repeated the trials for reliability purposes. CoP displacement was the main
      outcome measure. Regression analysis indicated that the Wii BB has excellent
      concurrent validity, and Bland-Altman plots showed good agreement between devices
      with small mean differences and no relationship between the difference and the
      mean. Intraclass correlation coefficients (ICCs) indicated modest-to-excellent
      test-retest reliability (ICC=0.64-0.85). Standard error of measurement and
      minimal detectable change were similar for both devices, except the 'eyes closed'
      condition, with greater standard error of measurement for the Wii BB. In
      conclusion, the Wii BB is shown to be a valid and reliable method to quantify CoP
      displacement in older adults. 

PMID- 24445864
TI  - [Granulosa cell tumors of the ovary].
AB  - Ovarian granulosa cell tumors (TGO) are rare neoplasms. They arise from sex cord
      stromal cells of the ovaries. They are characterized by their slow natural
      history, and their tendency to relapse long time after the initial diagnosis.
      Complete staging surgery of the disease is the cornerstone of treatment.
      Chemotherapy is indicated for localized tumors with a high risk of recurrence,
      and for recurrent or advanced tumors. Prolonged follow-up is recommended. 

PMID- 24445865
TI  - Efficacy of cyclin-dependent-kinase 9 inhibitors in a murine model of mixed
      lineage leukemia.
AB  - Mixed-lineage leukemia fusion proteins activate their target genes predominantly
      by stimulating transcriptional elongation. A core component necessary for this
      activity is cyclin-dependent kinase 9. Here we explored the effectiveness of
      small molecules targeting this enzyme as potential therapeutics. A screen of
      seven compounds with anti-CDK9 activity applied to a panel of leukemia cell lines
      identified flavopiridol and the experimental inhibitor PC585 as superior in
      efficacy with inhibitory concentrations in the submicromolar range. Both
      substances induced rapid dephosphorylation of the RNA polymerase II C-terminal
      domain, accompanied by downregulation of CDK9-dependent transcripts for MYC and
      HOXA9. Global gene expression analysis indicated the induction of a general
      stress response program, culminating in widespread apoptosis. Importantly, colony
      forming activity in leukemia lines and primary patient samples could be
      completely inhibited under conditions that did not affect native precursors from
      bone marrow. In vivo application in a mouse transplant model significantly
      delayed disease with PC585 showing also oral activity. These results suggest CDK9
      inhibition as novel treatment option for mixed-lineage leukemia. 

PMID- 24445866
TI  - MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host
      disease.

PMID- 24445869
TI  - Graphdiyne and graphyne: from theoretical predictions to practical construction.
AB  - Flat carbon (sp(2) and sp) networks endow the graphdiyne and graphyne families
      with high degrees of pi-conjunction, uniformly distributed pores, and tunable
      electronic properties; therefore, these materials are attracting much attention
      from structural, theoretical, and synthetic scientists wishing to take advantage
      of their promising electronic, optical, and mechanical properties. In this
      Review, we summarize a state-of-the-art research into graphdiynes and graphynes,
      with a focus on the latest theoretical and experimental results. In addition to
      the many theoretical predictions of the potential properties of graphdiynes and
      graphynes, we also discuss experimental attempts to synthesize and apply
      graphdiynes in the areas of electronics, photovoltaics, and catalysis. 

PMID- 24445868
TI  - Chronic neutrophilic leukemia with concurrent CSF3R and SETBP1 mutations: single
      colony clonality studies, in vitro sensitivity to JAK inhibitors and lack of
      treatment response to ruxolitinib.

PMID- 24445867
TI  - The CD37-targeted antibody-drug conjugate IMGN529 is highly active against human
      CLL and in a novel CD37 transgenic murine leukemia model.
AB  - Therapeutic regimens for chronic lymphocytic leukemia (CLL) have increasingly
      utilized monoclonal antibodies since the chimeric anti-CD20 antibody rituximab
      was introduced. Despite improved clinical outcomes, current CLL therapies are not
      curative. Therefore, antibodies with greater efficacy and novel targets are
      desirable. One promising target is CD37, a tetraspanin protein highly expressed
      on malignant B-cells in CLL and non-Hodgkin lymphoma. Although several novel CD37
      directed therapeutics are emerging, detailed preclinical evaluation of these
      agents is limited by lack of appropriate animal models with spontaneous leukemia
      expressing the human CD37 (hCD37) target. To address this, we generated a murine
      CLL model that develops transplantable hCD37+ leukemia. Subsequently, we
      engrafted healthy mice with this leukemia to evaluate IMGN529, a novel hCD37
      targeting antibody-drug conjugate. IMGN529 rapidly eliminated peripheral blood
      leukemia and improved overall survival. In contrast, the antibody component of
      IMGN529 could not alter disease course despite exhibiting substantial in vitro
      cytotoxicity. Furthermore, IMGN529 is directly cytotoxic to human CLL in vitro,
      depletes B-cells in patient whole blood and promotes killing by macrophages and
      natural killer cells. Our results demonstrate the utility of a novel mouse model
      for evaluating anti-human CD37 therapeutics and highlight the potential of
      IMGN529 for treatment of CLL and other CD37-positive B-cell malignancies. 

PMID- 24445870
TI  - Room temperature triplet state spectroscopy of organic semiconductors.
AB  - Organic light-emitting devices and solar cells are devices that create,
      manipulate, and convert excited states in organic semiconductors. It is crucial
      to characterize these excited states, or excitons, to optimize device performance
      in applications like displays and solar energy harvesting. This is complicated if
      the excited state is a triplet because the electronic transition is 'dark' with a
      vanishing oscillator strength. As a consequence, triplet state spectroscopy must
      usually be performed at cryogenic temperatures to reduce competition from non
      radiative rates. Here, we control non-radiative rates by engineering a solid
      state host matrix containing the target molecule, allowing the observation of
      phosphorescence at room temperature and alleviating constraints of cryogenic
      experiments. We test these techniques on a wide range of materials with
      functionalities spanning multi-exciton generation (singlet exciton fission),
      organic light emitting device host materials, and thermally activated delayed
      fluorescence type emitters. Control of non-radiative modes in the matrix
      surrounding a target molecule may also have broader applications in light
      emitting and photovoltaic devices. 

PMID- 24445871
TI  - A BODIPY-embedding miltefosine analog linked to cell-penetrating Tat(48-60)
      peptide favors intracellular delivery and visualization of the antiparasitic
      drug.
AB  - Therapeutic application of many drugs is often hampered by poor or denied access
      to intracellular targets. A case in point is miltefosine (MT), an orally active
      antiparasitic drug, which becomes ineffective when parasites develop
      dysfunctional uptake systems. We report here the synthesis of a fluorescent
      BODIPY-embedding MT analogue with appropriate thiol functionalization allowing
      linkage to the cell-penetrating Tat(48-60) peptide through disulfide or thioether
      linkages. The resulting constructs are efficiently internalized into the
      otherwise MT-invulnerable R40 Leishmania strain, resulting in fast parasite
      killing, and hence successful avoidance of the resistance. In the disulfide
      linked conjugate, an additional fluoro tag on the Tat moiety allows to monitor
      its reductive cleavage within the cytoplasm. Terminally differentiated cells such
      as peritoneal macrophages, impervious to MT unless infected by Leishmania, can
      uptake the drug in its Tat-conjugated form. The results afford proof-of-principle
      for using CPP vectors to avert drug resistance in parasites, and/or for tackling
      leishmaniasis by modulating macrophage uptake. 

PMID- 24445872
TI  - Sources of federal funding in plastic and reconstructive surgery research.
AB  - BACKGROUND: In the last several years, federal funding has become increasingly
      difficult to obtain. The purpose of this project was to define the level of
      federal funding among plastic surgeons in the modern era. METHODS: The authors
      evaluated members of the Plastic Surgery Research Council because of their
      expected invested interested in research. The authors collected information from
      1998 to 2012 on funding using curricula vitae and publically available online
      tools. Data on Plastic Surgery Foundation funding was also collected to determine
      its role in supporting federally funded investigators. RESULTS: Of 256
      individuals, the authors found 41 to be primary investigators on federally funded
      grants, with the majority receiving one to two awards. Common subtypes of awards
      included National Institutes of Health R01 (n = 15), K08 (n = 9), and R21 (n =
      6). Limited funding from the National Science Foundation and the Department of
      Defense was identified. Despite a steady number of available National Institutes
      of Health awards, plastic surgery recipients have grown in number over the past
      15 years. In a review of 20 years of Plastic Surgery Foundation awards, 113
      Plastic Surgery Research Council members (44.1 percent) were awardees, averaging
      1.8 awards per person. Twenty-nine Plastic Surgery Foundation awardees were also
      recipients of federal funding; 12 individuals received federal funding without
      prior Plastic Surgery Foundation funding. CONCLUSIONS: A search of plastic
      surgeons indicates a limited but increasing number of individuals receive federal
      funding. Plastic Surgery Foundation awards appear to be helpful in supporting
      investigators as they move to larger federal awards.

PMID- 24445873
TI  - Surgical treatment of nipple malposition in nipple-sparing mastectomy device
      based reconstruction.
AB  - BACKGROUND: This article discusses the senior author's (M.T.) experience with
      nipple-areola complex malposition following nipple-sparing mastectomy, surgical
      options for treatment, and an analysis of risk factors. METHODS: A retrospective
      review was conducted on a prospectively collected institutional review board
      approved database of nipple-sparing mastectomy cases with immediate device-based
      reconstruction performed between July of 2006 and October of 2012. Malposition
      was graded as mild (1 cm), moderate (2 cm), or severe (>3 cm) displacement.
      RESULTS: Three hundred nineteen nipple-sparing mastectomies were reviewed.
      Malposition occurred in 44 (13.79 percent). Significant factors were age (p <
      0.0001), diabetes mellitus (p = 0.0025), body mass index (p = 0.0093),
      preoperative sternal notch-to-nipple distance (p = 0.015), preoperative breast
      base width (p = 0.0001), periareolar mastectomy incision with lateral extension
      (p < 0.0001), prior radiation (p = 0.0004), prior lumpectomy (p = 0.0125),
      unilateral nipple-sparing mastectomy (p = 0.0004), and postoperative nipple
      areola complex ischemia (p = 0.0174). Smoking status, breast volume resected,
      implant size, ablative surgeon, acellular dermal matrix, and single-stage
      reconstruction were not significant. Nineteen patients were satisfied. Eight were
      not offered surgical correction because of an inadequate skin envelope. Eight had
      crescent mastopexy, three had implant exchange and pocket revision, four had free
      nipple grafts, and two had pedicled nipple transposition. There were no
      incidences of necrosis or malposition after surgical correction. CONCLUSIONS:
      Nipple-sparing mastectomy followed by immediate device-based reconstruction has a
      risk of nipple malposition. Various surgical procedures are available to correct
      nipple malposition based on clinical presentation and are safe in certain
      populations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24445874
TI  - New anatomical insights on the course and branching patterns of the facial
      artery: clinical implications of injectable treatments to the nasolabial fold and
      nasojugal groove.
AB  - BACKGROUND: Improper manipulation of injectable treatments to the face can result
      in disastrous vascular complications. The aim of the present study was to
      elucidate the detoured course of the facial artery and to provide detailed metric
      data regarding facial artery location with a view to helping physicians avoid
      iatrogenic vascular accidents during injectable treatments. METHODS: Sixty
      specimens from 35 embalmed cadavers (24 male and 11 female cadavers; mean age,
      70.0 years) and one fresh male cadaver (age, 62 years) were used for this study.
      RESULTS: In 56 cases (93.3 percent), the branches of the facial artery were
      observed at the vicinity of the nasolabial fold. The facial artery was located
      3.2 +/- 4.5 mm (mean +/- SD) lateral to the ala of the nose and 13.5 +/- 5.4 mm
      lateral to the oral commissure. It crossed the nasolabial fold in 33.9 percent of
      cases, and ascended within 5 mm of the nasolabial fold in 42.9 percent. The
      facial artery and detoured branches were found in 18 cases (30.0 percent). In the
      cases with detoured branches, the facial artery turned medially over the
      infraorbital area at 39.2 +/- 5.8 mm lateral to the facial midsagittal line and
      35.2 +/- 8.2 mm inferior to the plane connecting the medial epicanthi of both
      sides. The nasojugal portion of the detoured branch traveled along the inferior
      border of the orbicularis oculi and then ascended toward the forehead, forming
      the angular artery. CONCLUSION: This detailed vascular anatomy of the facial
      artery will promote safe clinical manipulations during injectable treatments to
      the nasolabial fold and nasojugal groove.

PMID- 24445875
TI  - The differing adipocyte morphologies of deep versus superficial midfacial fat
      compartments: a cadaveric study.
AB  - BACKGROUND: Anatomical studies show that facial fat is partitioned into distinct
      compartments, with the nasolabial fat pad in a superficial compartment and the
      deep medial cheek fat in a deep compartment. Gross morphologic differences may
      exist between these fat depots, but this has never been established at the
      cellular level. METHODS: Adipose tissue specimens from nasolabial fat and deep
      medial cheek fat pads were obtained from 63 cadaveric specimens (38 female and 25
      male cadavers) aged 47 to 101 years (mean, 71 years). Thirty-seven cadavers had a
      normal body mass index (<=25 kg/m) and 26 cadavers had a high body mass index
      (>25 kg/m). Cross-sectional areas of individual adipocytes were calculated
      digitally and averaged from histologic sections of the adipose tissue samples.
      RESULTS: The average adipocyte size of nasolabial fat is significantly (p <
      0.0001) larger than that of deep medial cheek fat. The average adipocyte size in
      both nasolabial and deep medial cheek fat is significantly (p < 0.0001) larger in
      subjects with high compared with low body mass index. Although the overall
      average adipocyte size is significantly (p < 0.0001) larger in female than in
      male subjects, this sexual dimorphism is lost in the nasolabial fat depots of
      overweight subjects and in the deep medial cheek depots of normal-weight
      subjects. CONCLUSIONS: The significantly smaller adipocyte size in deep medial
      cheek fat relative to nasolabial fat in elderly subjects supports the theory that
      deep and superficial facial fat pads are morphologically different. Future
      investigation of the metabolic and structural properties of these fat
      compartments will help us understand the different patterns of volumetric facial
      aging.

PMID- 24445876
TI  - The effects of biological lubricating molecules on flexor tendon reconstruction
      in a canine allograft model in vivo.
AB  - BACKGROUND: Using allograft is an attractive alternative for flexor tendon
      reconstruction because of the lack of donor-site morbidity, and better matching
      to the intrasynovial environment. The purpose of this study was to use biological
      lubricant molecules to modify the graft surface to decrease adhesions and improve
      digit function. METHODS: Twenty-eight flexor digitorum profundus tendons from the
      second and fifth digits of 14 dogs were lacerated and repaired to create a model
      with repair failure and scar digit for tendon reconstruction. Six weeks after the
      initial operation, the tendons were reconstructed with flexor digitorum profundus
      allograft tendons obtained from canine cadavers. One graft tendon in each dog was
      treated with saline as a control and the other was treated with carbodiimide
      derivatized hyaluronic acid and gelatin plus lubricin. Six weeks postoperatively,
      digit function, graft mechanics, and biology were analyzed. RESULTS: Allograft
      tendons treated with carbodiimide-derivatized hyaluronic acid-lubricin had
      decreased adhesions at the proximal tendon/graft repair and within the flexor
      sheath, improved digit function, and increased graft gliding ability. The
      treatment also reduced the strength at the distal tendon-to-bone repair, but the
      distal attachment rupture rate was similar for both graft types. Histologic
      evaluation showed that viable cells migrated to the allograft, but these were
      limited to the tendon surface. CONCLUSIONS: Carbodiimide-derivatized hyaluronic
      acid-lubricin treatment of tendon allograft improves digit functional outcomes
      after flexor tendon reconstruction. However, delayed bone-to-tendon healing
      should be a caution. Furthermore, the cell infiltration into the allograft tendon
      substance should be a target for future studies, to shorten the allograft self
      regeneration period.

PMID- 24445878
TI  - Effects of hypotensive anesthesia on blood transfusion rates in craniosynostosis
      corrections.
AB  - BACKGROUND: Hypotensive anesthesia is routinely used during craniosynostosis
      corrections to reduce blood loss. Noting that cerebral oxygenation levels often
      fell below recommended levels, the authors sought to measure the effects of
      hypotensive versus standard anesthesia on blood transfusion rates. METHODS: One
      hundred children undergoing craniosynostosis corrections were randomized
      prospectively into two groups: a target mean arterial pressure of either 50 mm Hg
      or 60 mm Hg. Aside from anesthesiologists, caregivers were blinded and strict
      transfusion criteria were followed. Multiple variables were analyzed, and
      appropriate statistical testing was performed. RESULTS: The hypotensive and
      standard groups appeared similar, with no statistically significant differences
      in mean age (46.5 months versus 46.5 months), weight (19.25 kg versus 19.49 kg),
      procedure [anterior remodeling (34 versus 31) versus posterior (19 versus 16)],
      or preoperative hemoglobin level (13 g/dl versus 12.9 g/dl). Intraoperative mean
      arterial pressures differed significantly (56 mm Hg versus 66 mm Hg; p < 0.001).
      The captured cell saver amount was lower in the hypotensive group (163 cc versus
      204 cc; p = 0.02), yet no significant differences were noted in postoperative
      hemoglobin levels (8.8 g/dl versus 9.3 g/dl). Fifteen of 100 patients (15
      percent) received allogenic transfusions, but no statistically significant
      differences were noted in transfusion rates between the hypotensive [nine of 53
      (17.0 percent)] and standard anesthesia [six of 47 (13 percent)] group (p =
      0.056). CONCLUSIONS: No significant difference in transfusion requirements was
      found between hypotensive and standard anesthesia during craniosynostosis
      corrections. Considering potential benefits of improved cerebral blood flow and
      total body perfusion, surgeons might consider performing craniosynostosis
      corrections without hypotension. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 24445877
TI  - Fat grafting to the hand in patients with Raynaud phenomenon: a novel therapeutic
      modality.
AB  - BACKGROUND: Raynaud phenomenon causes progressively decreasing blood flow to the
      extremities, resulting from an imbalance between vasoconstriction and
      vasodilation. Treatment options include biofeedback, phosphodiesterase
      inhibitors, calcium channel inhibitors, botulinum toxin injection, or surgical
      sympathectomy. The authors propose fat grafting to the hands as a method to delay
      progression of the disease. METHODS: Indications included symptomatic Raynaud
      phenomenon with failure of previous management. Fat is harvested from abdominal
      depots. Approximately 30 ml of decanted fat is injected by means of blunt
      cannulae: 10 to 15 ml in the dorsum of the hand, 2 to 3 ml in the snuffbox, 1 to
      2 ml in each dorsal webspace, 3 to 4 ml along the superficial palmar arch, 1 to 2
      ml in volar webspaces 2 to 4, and 2 to 3 ml in the first webspace. Patients
      underwent preoperative and postoperative laser speckle imaging study to assess
      changes in perfusion. RESULTS: A total of 13 patients were treated (21 hands).
      Twelve patients had undergone prior botulinum toxin injection, and 11 patients
      had prior sympathectomies. Findings included reduced pain (average reduction,
      6.86 of 10 to 2.38 of 10), fewer cold attacks, improved skin and soft-tissue
      texture, decrease in ulcerations, and patient-reported improved function. Three
      patients had no changes. Increased blood flow per imaging was noted in five of 11
      hands tested. Six patients had decreased readings on laser imaging. None of the
      laser speckle imaging changes were statistically significant, and they did not
      correlate clinically. There were no major complications. CONCLUSIONS: Preliminary
      results of fat grafting to the hands of patients with Raynaud phenomenon revealed
      improved symptomatology with evidence suggestive of measurably increased
      perfusion in some cases. Fat grafting may benefit the management of this patient
      population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24445879
TI  - Establishing cephalometric landmarks for the translational study of Le Fort-based
      facial transplantation in Swine: enhanced applications using computer-assisted
      surgery and custom cutting guides.
AB  - BACKGROUND: Le Fort-based, maxillofacial allotransplantation is a reconstructive
      alternative gaining clinical acceptance. However, the vast majority of single-jaw
      transplant recipients demonstrate less-than-ideal skeletal and dental
      relationships, with suboptimal aesthetic harmony. The purpose of this study was
      to investigate reproducible cephalometric landmarks in a large-animal model,
      where refinement of computer-assisted planning, intraoperative navigational
      guidance, translational bone osteotomies, and comparative surgical techniques
      could be performed. METHODS: Cephalometric landmarks that could be translated
      into the human craniomaxillofacial skeleton, and that would remain reliable
      following maxillofacial osteotomies with midfacial alloflap inset, were sought on
      six miniature swine. Le Fort I- and Le Fort III-based alloflaps were harvested in
      swine with osteotomies, and all alloflaps were either autoreplanted or
      transplanted. Cephalometric analyses were performed on lateral cephalograms
      preoperatively and postoperatively. Critical cephalometric data sets were
      identified with the assistance of surgical planning and virtual prediction
      software and evaluated for reliability and translational predictability. RESULTS:
      Several pertinent landmarks and human analogues were identified, including
      pronasale, zygion, parietale, gonion, gnathion, lower incisor base, and
      alveolare. Parietale-pronasale-alveolare and parietale-pronasale-lower incisor
      base were found to be reliable correlates of sellion-nasion-A point angle and
      sellion-nasion-B point angle measurements in humans, respectively. CONCLUSIONS:
      There is a set of reliable cephalometric landmarks and measurement angles
      pertinent for use within a translational large-animal model. These
      craniomaxillofacial landmarks will enable development of novel navigational
      software technology, improve cutting guide designs, and facilitate exploration of
      new avenues for investigation and collaboration.

PMID- 24445880
TI  - Vascularization of the facial bones by the facial artery: implications for full
      face allotransplantation.
AB  - BACKGROUND: The maxillary artery is recognized as the main vascular supply of the
      facial bones; nonetheless, clinical evidence supports a codominant role for the
      facial artery. This study explores the extent of the facial skeleton within a
      facial allograft that can be harvested based on the facial artery. METHODS:
      Twenty-three cadaver heads were used in this study. In 12 heads, the facial,
      superficial temporal, and maxillary arteries were injected. In one head, facial
      artery angiography was performed. Ten facial allografts were raised. The soft
      tissues were dissected to show the arterial anastomotic connections. Radiographs
      and computed tomographic scans were obtained. RESULTS: Constant anastomosis
      between the facial, inferior alveolar, and infraorbital arteries at the mental
      and infraorbital foramina were found. The facial artery vascularized the
      homolateral mandibular symphysis, body, and ramus. The condylar and coronoid
      processes were vascularized in 67 percent of the allografts. The homolateral
      maxilla was contrasted in all allografts. The alveolar and palatine processes
      contained the contrast in 83 percent of specimens. The maxillary process of the
      zygomatic bone was perfused in all allografts, followed by the body, frontal (83
      percent), and temporal processes (67 percent). The nasal lateral wall and septum
      were vascularized in 83 percent of the allografts. The medial and lateral orbital
      walls and the orbital floor were stained in all specimens. The zygomatic process
      of the temporal bone was the least perfused bone. CONCLUSION: A composite
      allograft containing 90 to 95 percent of the facial bones can be based on
      bilateral facial arteries.

PMID- 24445881
TI  - The thin gluteal artery perforator free flap to resurface the posterior aspect of
      the leg and foot.
AB  - BACKGROUND: The authors evaluated the clinical application of the gluteal artery
      perforator free flap harvested above the superficial fascia as a new approach to
      reconstruct soft-tissue defects of the posterior aspect of the lower limb.
      METHODS: Between September of 2010 and August of 2013, 27 thin flaps were used to
      reconstruct lower extremity defects in 27 patients. All flaps were elevated on
      the superficial fascia plane and based on a single perforator from either the
      superior or inferior gluteal artery. RESULTS: With the exception of two flaps
      that healed secondarily after partial loss, all flaps survived completely.
      Average flap thickness was 8.5 mm (range, 5 to 11 mm). The average flap size was
      125 cm (range, 9 * 4 cm to 25 * 12 cm). The average pedicle length was 5.5 cm
      (range, 3 to 8 cm.). The average artery diameter was 0.65 mm (range, 0.4 to 1.3
      mm). During the average follow-up of 13 months (range, 2 to 35 months), all flaps
      showed good contour and did not require any secondary revisions. CONCLUSIONS: The
      gluteal artery perforator free flap provides a thin flap for ideal contour,
      minimizes the operative risks of changing the patient's position
      intraoperatively, and conceals the donor site with minimal morbidity. However,
      the pedicle can be short and supermicrosurgery skills may be needed to
      accommodate the short pedicle. Overall, this new approach of using a thin gluteal
      artery perforator free flap to reconstruct the posterior aspect of the leg and
      foot can be considered a feasible option. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 24445882
TI  - The influence manufacturers have on negative-pressure wound therapy research.
AB  - BACKGROUND: Studies investigating the effects of negative-pressure wound therapy
      using the Chariker-Jeter system (gauze-based interface) and the vacuum-assisted
      closure system often have outcomes that favor one particular system. This study
      attempts to examine whether manufacturer involvement could be related to the
      outcomes of these scientific studies. METHODS: A literature review was undertaken
      to identify a cohort of studies that compared these two forms of negative
      pressure wound therapy. Clinical outcomes studies, basic research studies, and
      published conference abstracts were included. Allthe articles' abstracts and
      conclusions were given to five surgeons, who were blinded to the titles and
      authors. They were individually asked to record what they would consider to be
      the take-home message of each article (in terms of which system is superior).
      After categorizing each study according to the system that it appears to favor,
      the level of manufacturer involvement in each study was evaluated. The
      relationship between the outcome of a study and the level of manufacturer
      involvement in that study was then investigated. RESULTS: Of the total of 24
      studies found to match the inclusion criteria, 22 were considered to favor a
      particular system (the other two were categorized as impartial). Of the 24
      studies, 19 had some form of manufacturer involvement. Of the 19 that had some
      form of manufacturer involvement, 18 had outcomes that were deemed beneficial to
      the involved manufacturer, whereas one was deemed to have an impartial outcome.
      CONCLUSIONS: This study suggests that manufacturer involvement in these studies
      (regardless of level) correlates with the outcomes being beneficial to the
      involved manufacturer in almost all cases. Potential reasons for this and the
      implications thereof are discussed.

PMID- 24445883
TI  - Diagnostic errors in interpretation of pediatric musculoskeletal radiographs at
      common injury sites.
AB  - BACKGROUND: Extremity pain represents one of the most common reasons for
      obtaining conventional radiographs in childhood. Despite the frequency of these
      examinations little is known about the incidence of diagnostic errors by
      interpreting pediatric radiologists. OBJECTIVE: The purpose of this study was to
      develop a standard error rate of pediatric radiologists by double-reading of
      extremity radiographs (elbow, wrists, knees and ankles) in children presenting
      with a history of trauma or pain. MATERIALS AND METHODS: During a 6-month period
      all major extremity radiographs (excluding digits) obtained at a large pediatric
      referral hospital for evaluation of pain or trauma were reviewed by two senior
      pediatric radiologists and compared to the official interpretation. All
      radiographs were interpreted initially by a board-certified pediatric radiologist
      with a Certificate of Added Qualification (CAQ). We reviewed 3,865 radiographic
      series in children and young adults 2-20 years of age. We tabulated misses and
      overcalls. We did not assess the clinical significance of the errors. RESULTS:
      There were 61 miss errors and 44 overcalls in 1,235 abnormal cases and 2,630
      normal cases, for a 1.6% miss rate and a 1.1% overcall rate. Misses and overcalls
      were most common in the ankle. CONCLUSION: Interpretive errors by pediatric
      radiologists reviewing certain musculoskeletal radiographs are relatively
      infrequent. Diagnostic errors in the form of a miss or overcall occurred in 2.7%
      of the radiographs.

PMID- 24445885
TI  - Update on colistin in clinical practice.
AB  - Considerable progress has been made in the last decade towards better
      understanding of the optimal clinical use of colistin. It has become evident that
      higher intravenous (iv) colistin methanesulfonate (CMS) doses are important,
      probably with the addition of a loading dose in critically ill patients. Higher
      CMS doses lead to increased risk of nephrotoxicity, which seems reversible in
      most cases. Intravenous colistin is reasonably efficacious, but should continue
      to be considered only in the absence of safer alternatives. Although
      theoretically appealing, there is insufficient evidence to support inhaled
      colistin mono-therapy in non-cystic fibrosis patients. Moreover, the balance of
      evidence available at present is not in favor of adjunctive inhaled colistin
      therapy. Intrathecal or intra-ventricular colistin administration are appropriate
      options for neurosurgical meningitis caused by colistin-susceptible, multidrug
      resistant gram-negative bacteria. Ongoing randomized, controlled trials will
      hopefully help decide if combining colistin with a carbapenem, fosfomycin, or
      rifampicin is of clinical advantage. 

PMID- 24445886
TI  - Effectiveness and complication rates of tension-free vaginal tape, transobturator
      tape, and tension-free vaginal tape-obturator in the treatment of female stress
      urinary incontinence in a medium- to long-term follow up. Meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: To evaluate the effectiveness and complications of tension-free
      vaginal tape (TVT), transobturator tape (TOT), and tension-free vaginal tape
      obturator (TVT-O) in a medium- to long-term follow up. METHODS: We searched
      PubMed, EMBASE, Cochrane database, ClinicalTrials.gov, Google Scholar, and the
      International Continence Society (ICS) website from August to December 2012 in
      Guangzhou First People's Hospital, Guangzhou, China. Randomized controlled trials
      (RCTs) comparing the effectiveness and complications of TVT, TOT, and TVT-O were
      selected. RESULTS: Forty RCTs were included. The TVT and TOT had similar
      subjective (risk ratio [RR]: 0.99; 95% confidence interval [CI]: 0.93-1.04), and
      objective cure rates (RR: 0.96; 95% CI: 0.70-1.32). However, TVT had a reduced
      risk of groin/thigh pain (RR: 0.33; 95% CI: 0.18-0.59). The subjective (RR: 1.02;
      95% CI: 0.97-1.06) and objective cure rates (RR: 1.02; 95% CI: 0.99-1.06) of TVT
      O were similar to TVT, but TVT had a higher risk of bladder perforations (RR:
      2.29; 95% CI: 1.18-4.45). The TVT-O and TOT had similar subjective (RR: 0.99; 95%
      CI: 0.93-1.06), and objective cure rates (RR: 1.01; 95% CI: 0.95-1.07). However,
      TVT-O had a lower risk of vaginal erosion rates (RR: 0.16; 95% CI: 0.03-0.89).
      CONCLUSION: The subjective and objective cure rates of stress urinary
      incontinence were similar among TVT, TOT, and TVT-O in a medium- to long-term
      follow up. The TVT had a higher risk of bladder perforation than TVT-O, and a
      lower risk of groin/thigh pain than TOT, and TVT-O had a lower risk of vaginal
      erosion rates than TOT.

PMID- 24445887
TI  - Comparison of herbal-based and synthetic hemostatic agents for efficacy on a rat
      partial nephrectomy model. Experimental study.
AB  - OBJECTIVE: To compare the efficacy of herbal based and synthetic hemostatic
      agents in partial nephrectomy. METHODS: Our experimental study was carried out at
      the Ankara Training and Research Hospital, Ankara, Turkey between May and
      November 2012. Twenty rats were randomly divided into 4 groups. Intracorporeal
      sutures (group K), TachoSil (group T), HaemoCer (group H), and Ankaferd Blood
      Stopper (group A) were used to achieve hemostasis in partial nephrectomy. Warm
      ischemia time (WIT), hemostasis time (HT), and blood loss for all groups were
      measured. The specimens were examined histopathologically and electron
      microscopically after sacrificing the rats. RESULTS: The fastest hemostasis was
      detected in group T, followed by group H, and group A. The WIT and HT were
      significantly different for all groups (p<0.001). The greatest blood loss was
      found in group K. The histopathologic examination revealed that the giant cell
      reaction in group K was significantly more than in group H and group A (p<0.001).
      No pathologic findings were observed in the ultrastructural examination of
      specimens taken from group K. On ultrastructural examination of group T, tubule
      cells had many vacuoles in their cytoplasm with marked intracellular edema.
      Ultrastructural findings for groups H and A were similar. CONCLUSION: At the
      histopathologic and ultrastructural levels, herbal-based hemostatic agents had a
      positive impact on renal tissue and glomerular function when applied during
      partial nephrectomy.

PMID- 24445888
TI  - The rates of sputum conversion among new smear positive open pulmonary
      tuberculosis patients treated under directly observed treatment, short course
      strategy.
AB  - OBJECTIVE: To evaluate effectiveness of directly observed treatment short course
      (DOTS) by monthly sputum conversion rates at first, second, and third month in
      newly diagnosed patients of pulmonary tuberculosis (TB) (category-1), and to
      study patterns of lesions on chest radiographs and their correlation to smear
      sputum positivity, also to record reaction to Mantoux tuberculin skin test (TST)
      in active TB patients. METHODS: This prospective cohort study was conducted among
      100 newly diagnosed patients of open pulmonary tuberculosis CAT-1, admitted and
      treated under DOTS, at the Tuberculosis Center, Dammam Medical Complex, Dammam,
      Kingdom of Saudi Arabia between July to December 2010. Chest radiographs were
      studied for the patterns of lesions and their correlation to the grades of sputum
      positivity. Three fasting state sputum specimens were tested on 3 consecutive
      days by direct smear microscopy at first, second, and third month. As per DOTS,
      intensive phase treatment was extended for another 4 weeks in those still
      positive at the end of 2 months. Mantoux TST was performed on all patients with
      tuberculin purified protein derivative-RT-23 2TU. RESULTS: The overall sputum
      conversion rate observed at the first month was 56%, 76% on the second month, and
      94% on the third month. Reaction to TST of more than 10 mm was recorded in most
      of the studied patients (97%). CONCLUSION: The DOTS is an appropriate strategy
      for early and progressive conversion of smear positive patients to break the
      chain of infection, which is epidemiologically important for the control,
      elimination, and eradication of TB.

PMID- 24445889
TI  - Determination of the median effective dose for motor block of intrathecally
      administered different concentrations of bupivacaine in younger patients. The
      influence of solution concentration.
AB  - OBJECTIVE: To determine the median effective dose (ED50) for motor block of
      intrathecally administered different concentrations of bupivacaine in younger
      patients. METHODS: This study was conducted at the Department of Anesthesiology,
      The First College of Clinical Medical Science, China Three Gorges University,
      China, on 40 American Society of Anaesthesiologists (ASA) I-II younger patients
      (18-40 years) undergoing lower limb surgery. These patients were classified into
      2 groups according to a computer-generated random number table (Group A - 0.375%
      bupivacaine, and Group B - 0.75% bupivacaine). Spinal anesthesia was established
      by bolus administration of various up-and-down doses of 0.375%, or 0.75% plain
      bupivacaine. These up-and-down doses were determined by Dixon's up-and-down
      method. The first patient of each group was given 7.5 mg bupivacaine, and the
      testing interval was set at 0.75 mg. The dose was up, or down, 0.75 mg increments
      according to the failure or success of the preceding patient's motor block. The
      degree of motor block after intrathecal administration of bupivacaine was
      evaluated by the modified Bromage and Hip motor function score. The ED50 were
      estimated from the up-down sequences using the method of Dixon and Massey.
      RESULTS: Our results showed that ED50 for motor block of intrathecal bupivacaine
      was 8.890 mg in Group A, and 9.998 mg in Group B, and the relative motor blocking
      potency ratio was 1.12. CONCLUSION: The ED50 for motor block of intrathecally
      administered bupivacaine with higher concentration was slightly higher than that
      of a lower concentration.

PMID- 24445890
TI  - Transpedicular intracorporeal grafting for patients with thoracolumbar burst
      fractures.
AB  - OBJECTIVE: To evaluate the efficacy of reinforcing short-segment fixation with
      transpedicular intracorporeal grafting in restoring vertebral body height and
      preventing loss of correction in patients with thoracolumbar burst fractures.
      METHODS: This retrospective study was carried out from the Affiliated Hospital of
      Jiangsu University, Jiangsu, China. Forty-six patients with thoracolumbar burst
      fractures without neurological deficit were operatively treated between July 2008
      and June 2011. Patients in group A (n=21) were treated by short-segment fixation
      with transpedicular intracorporeal grafting, whereas patients in group B (n=25)
      were treated by short-segment fixation without bone grafting. The preoperative,
      postoperative, and follow-up radiographs (anterior, middle, posterior vertebral
      height, and local kyphosis angle) were evaluated. RESULTS: All 46 patients in
      both groups obtained satisfactory reduction of fractured vertebrae. There were no
      significant differences between the 2 groups according to the improvement of body
      height and local kyphosis angle. However, correction losses were observed in both
      groups. Less losses of anterior body height (p=0.0007), middle body height
      (p<0.0001), and local kyphosis angle (p=0.0447) were detected in group A than
      group B. The rate of failure in group A (4.8%) was significantly lower than that
      in group B (28.0%) (p=0.0383). CONCLUSION: Reinforcement of short-segment
      fixation with transpedicular intracorporeal grafting can effectively restore
      vertebral body height and prevent loss of correction for patients with
      thoracolumbar burst fractures.

PMID- 24445891
TI  - Central corneal pachymetry in Yemeni patients undergoing refractive surgery.
AB  - OBJECTIVE: To assess the preoperative central corneal thickness (CCT) of myopic
      and/or astigmatism patients presenting for refractive surgery in a tertiary
      hospital in Yemen. METHODS: In this hospital-based cross-sectional study, 2,304
      subjects aged 18-50 years with myopia and myopic astigmatism who presented to the
      refractive surgery unit were recruited. Data for the current study was collected
      from our electronic pool of patients presenting to the refractive surgery clinics
      in Yemen Magrabi Hospital, Sana'a, Yemen, between January 2006 and December 2008.
      The inclusion criteria were absence of corneal or anterior segment disease,
      glaucoma, and any ocular surgery. Central corneal thickness was assessed by
      ultrasound pachymetry. Data from the right eye only was analyzed. RESULTS: All
      patients were Yemeni citizens, where the majority (1248; 54.2%) were women with a
      mean (+/-SD) age of 26.74 (+/-6.1), range 18-50 years. The mean (+/-SD) CCT was
      521.7 (+/-31.62), range 432-643 um. The measured CCT was independent of gender
      (p=0.567) and did not differ between both eyes (p=0.371). Corneal thickness
      increased with age, correlated to vision (p=0.027), keratometric readings (K1 ,
      K2) (p<0.001 for both), and increased with the increase in severity of myopia
      (p=0.026). CONCLUSION: Yemeni patients have thinner CCT compared to other
      populations. Refractive surgeons should be careful in choosing the suitable
      procedures. The available cornea for ablation in Laser-Assisted in situ
      Keratomileusis (LASIK) is very limited. Possible alternative treatments; namely
      photorefractive keratectomy (PRK) and phakic intraocular lens implantation
      options should be discussed with patients prior to surgery.

PMID- 24445892
TI  - Self-reported comfort with tracheostomy tube care. Cross-sectional survey of non
      ear, nose and throat health care professionals.
AB  - OBJECTIVE: To assess self-reported comfort of non-ear, nose and throat (ENT)
      health professionals in tracheostomy care and identify its associated factors.
      METHODS: This was a cross-sectional survey of non-ENT health care professionals,
      carried out from December 2011 to February 2013 at the Prince Sultan Military
      Medical City, and King Faisal Specialist Hospital & Research Centre, Riyadh,
      Kingdom of Saudi Arabia. A self-administered questionnaire was used to collect
      data on self-rated comfort levels in performing tracheostomy tube change and
      factors, such as speciality, duration of dedicated ENT rotation in medical
      school, and years of experience as a practicing consultant. RESULTS: A total of
      71 non-ENT health professionals participated in the survey. The response rate was
      100%. Overall, one out of every 4 participants (26.8%) rated their comfort level
      in tracheostomy tube change as 'fair or poor', 38% as good, and only 35.2% as
      excellent. Comfort level was the highest among anesthesiologists (94.1%), and
      intensivists (78.9%). In the multivariate analysis, physicians who reported ever
      performing tracheostomy tube change as a resident were significantly more likely
      to report comfort than their counterparts without such exposure (adjusted odds
      ratio: 7.09; 95% confidence interval: 1.90-26.40; p=0.003). When asked if there
      should be a mandatory course on tracheostomy care in tertiary care hospitals,
      most of the participants (60-72%), irrespective of their speciality, training and
      experience, replied in the affirmative. CONCLUSION: Non-ENT health professionals
      involved in airway care had a low level of self-rated comfort with tracheostomy
      tube care suggesting the need for periodic refresher training to address this
      gap.

PMID- 24445893
TI  - Poor vitamin D supplementation in infants. Cross-sectional study of maternal
      practices and awareness of vitamin D supplementation in infants in Al-Ahsa,
      Eastern Saudi Arabia.
AB  - OBJECTIVE: To describe the maternal practices and awareness of vitamin D
      supplementation in infants, and factors affecting these practices in Eastern
      Saudi Arabia. METHODS: A cross-sectional study was conducted with 606 mothers
      attending community-based primary health centers in Al-Ahsa, Eastern Saudi Arabia
      between March and April 2012. A 22-item questionnaire was used to assess the
      socio-demographic data of both infants and mothers, feeding methods, nursing
      practices including vitamin D supplementation, and mothers' awareness regarding
      vitamin D supplementation in infants by face-to-face interview. Chi-squared test
      was used to assess significant differences among these practices. Significant
      variables were subjected to multiple logistic regression. A p-value of 0.05 was
      used to indicate statistical significance. RESULTS: The response was 91%. Forty
      percent of mothers were not giving their infants vitamin D at the time of
      contact. More than 40% of the mothers were not aware of, and they were not
      offered advice on the need to give vitamin D to their infants. Lack of physician
      advice (odds ratio 42), and poor maternal awareness of the necessity to give
      vitamin D to their infants (odds ratio - 2.676) are the most significant factors
      related to the absence of vitamin D supplementation in infants (p<0.05).
      CONCLUSION: Vitamin D supplementation during the first year of infancy is low.
      This is most likely due to the lack of maternal awareness and physician neglect
      in providing advice to mothers regarding vitamin D supplementation in infants.

PMID- 24445894
TI  - Relationship between head posture and anterior-posterior skeletal patterns in a
      group of female patients.
AB  - OBJECTIVE: To evaluate the relationship between head posture and anteroposterior
      skeletal patterns in female adult patients. METHODS: The study included 75
      lateral cephalograms of orthodontic patients in the age range of 18-25 years. The
      study was conducted from May 2012 to January 2013 at the College of Dentistry,
      King Saud University, Riyadh, Kingdom of Saudi Arabia. The lateral cephalograms
      were divided into 3 groups based on the anterior-posterior skeletal relationship
      angle: skeletal class I, II, and III. Twenty-three craniofacial morphological
      variables were identified and used. The Kruskal-Wallis and Mann-Whitney U tests
      were used to determine significant differences among the 3 skeletal
      classifications. The Spearman correlation coefficient between the cervical
      lordosis angle and the cervical curvature with the postural variables were
      estimated. Significance was set at the p<0.05 level. RESULTS: Significant
      differences were observed in the mandibular plane inclination between class I and
      II (p<0.04), and between class II and III (p<0.028). Cervical curvature showed a
      significance difference between class I and II, and between class I and III
      (p<0.000). In Class I, II, and III the cervical lordosis angle positively
      correlated with the upper and middle parts of the cervical column. Cervical
      curvature correlated negatively with the upper part of the cervical column in
      class I, while positively correlated in class II and III. The class III group
      showed a more forward head posture, while the class II group showed a greater
      head extension. CONCLUSION: No clear relationship was found between head posture
      and the different skeletal patterns, and it does not seem to play a significant
      role in the development of different anteroposterior skeletal relationships.

PMID- 24445895
TI  - Community pharmacists' knowledge of isotretinoin safety.
AB  - OBJECTIVE: To explore the practice and knowledge of community pharmacists in
      Saudi Arabia regarding dispensing isotretinoin-containing products. METHODS: This
      was a cross-sectional study conducted in 2012 that included community pharmacists
      from 3 cities in Saudi Arabia. A validated and piloted self-administered survey
      collected demographics and information on the pharmacist's knowledge regarding
      isotretinoin precautions, as well as his dispensing, and counseling practices.
      RESULTS: One hundred and sixteen questionnaires were returned with a 72.5%
      response rate. Only around half of the participants (56%) knew the correct
      pregnancy risk classification category for oral isotretinoin. Most participants
      (78%) correctly identified teratogenicity as the most serious risk associated
      with the use of oral isotretinoin. However, only 6.2% of the pharmacists
      recommended using 2 methods of contraception. Almost one-fifth of the pharmacists
      dispensed isotretinoin without a prescription. Finally, 11% of the pharmacists
      did not ask whether the patient performed a pregnancy test prior to dispensing
      oral isotretinoin. CONCLUSION: Pharmacists at community pharmacies are not
      adequately aware of the risks for female patients using isotretinoin.
      Additionally, an alarming proportion of pharmacists dispense isotretinoin without
      a prescription. It is essential to implement risk minimization plans for certain
      medications to limit and prevent adverse drug reactions.

PMID- 24445896
TI  - Salmonella bacilli negative image recognized on Diff-Quik stain from pleural
      fluid cytology.
AB  - Understanding the significance of cytopathological tests in evaluating various
      infectious processes have become very essential nowadays, as it is a safe, fast,
      and cost-effective procedure. We present a case of a 52-year-old male with
      Salmonella empyema where the causative organisms were initially identified on
      cytology, and subsequently confirmed by microbiological culture. Diff-Quik
      stained smears showed many colorless, slender, fat short bacilli, which were
      visualized against the blue-gray background of the smear. These bacilli were
      identified both intracellularly inside the histiocytes and neutrophils cytoplasm
      as well as extracellularly in the smear background. We consider that this
      negative image represents the organism and its capsule creating an area that did
      not take the Diff-Quik stain. The patient was treated accordingly with suitable
      antibiotics. A brief discussion of this interesting finding in such a rare
      infection with pertinent literature review is presented. 

PMID- 24445897
TI  - Maxillary sinus nodular fasciitis.
AB  - Nodular fasciitis is a rare and benign inflammatory condition; however, it can be
      misdiagnosed as a malignant lesion. We report a unique case of nodular fasciitis
      arising from the maxillary sinus in a 2-year-old child. Our English literature
      review (PubMed search), revealed a total of 3 cases published as nodular
      fasciitis in the para-nasal sinuses, each with a different management approach. 

PMID- 24445898
TI  - The cost of dental caries in Saudi Arabia. Putting numbers into context.

PMID- 24445899
TI  - Quality of undergraduate critical care medical education in the Kingdom of Saudi
      Arabia. Where do we stand?

PMID- 24445900
TI  - Comment on biomedical research in Saudi Arabia.

PMID- 24445901
TI  - DNA-A of a highly pathogenic Indian cassava mosaic virus isolated from Jatropha
      curcas causes symptoms in Nicotiana benthamiana.
AB  - Jatropha curcas mosaic disease (JcMD) is a newly emerging disease that has been
      reported in Africa and India. Here, we report the complete nucleotide sequence of
      a new Indian cassava mosaic virus isolate (ICMV-SG) from Singapore. Infection of
      ICMV-SG showed more severe JcMD in Jatropha curcas and Nicotiana benthamiana than
      the other ICMV isolates reported previously, though ICMV-SG shares high sequence
      identity with the other ICMV isolates. Agroinfectious DNA-A alone sufficiently
      induced systemic symptoms in N. benthamiana, but not in J. curcas. Results from
      agroinfection assays showed that systemic infection of ICMV-SG in J. curcas
      required both DNA-A and DNA-B components.

PMID- 24445903
TI  - Early dipeptide repeat pathology in a frontotemporal dementia kindred with
      C9ORF72 mutation and intellectual disability.
AB  - Familial cases of frontotemporal dementia (FTD) provide an opportunity to study
      the pathophysiology of this clinically diverse condition. The C9ORF72 mutation is
      the most common cause of familial FTD, recent pathological descriptions challenge
      existing TDP-43 based hypotheses of sporadic FTD pathogenesis. Non-ATG dependent
      translation of the hexanucleotide expansion into aggregating dipeptide repeat
      (DPR) proteins may represent a novel pathomechanism. We report detection of the
      DPR aggregates very early in C9ORF72 FTD development and also describe childhood
      intellectual disability as a clinical feature preceding dementia. The index case
      presented with psychiatric symptoms, progressing into typical FTD. Autopsy
      revealed extensive neuronal DPR aggregates but only minimal TDP-43 pathology. Her
      intellectually disabled elder son, also carrying the C9ORF72 mutation, died aged
      26 years and at autopsy only DPR aggregates without TDP-43 were found. A second
      son also has intellectual disability, his C9ORF72 status is unknown, but
      chromosomal microarray revealed no other cause of disability. These cases both
      extend the existing phenotype of C9ORF72 mutation and highlight the potential
      significance of DPR translation early in disease development. 

PMID- 24445904
TI  - Room temperature decarboxylative trifluoromethylation of alpha,beta-unsaturated
      carboxylic acids by photoredox catalysis.
AB  - A visible-light-induced decarboxylative trifluoromethylation of alpha,beta
      unsaturated carboxylic acids, which uses the Togni reagent as the CF3 source is
      disclosed. The corresponding trifluoromethylated alkenes were obtained in
      moderate to high yields with excellent functional group tolerance at ambient
      temperature. Preliminary mechanistic analyses suggest a radical-type mechanism. 

PMID- 24445902
TI  - Plant miRNAome and antiviral resistance: a retrospective view and prospective
      challenges.
AB  - MicroRNAs (miRNAs) are small regulatory RNAs that play a defining role in post
      transcriptional gene silencing of eukaryotes by either mRNA cleavage or
      translational inhibition. Plant miRNAs have been implicated in innumerable growth
      and developmental processes that extend beyond their ability to respond to biotic
      and abiotic stresses. Active in an organism's immune defence response, host
      miRNAs display a propensity to target viral genomes. During viral invasion, these
      virus-targeting miRNAs can be identified by their altered expression. All the
      while, pathogenic viruses, as a result of their long-term interaction with
      plants, have been evolving viral suppressors of RNA silencing (VSRs), as well as
      viral-encoded miRNAs as a counter-defence strategy. However, the gene silencing
      attribute of miRNAs has been ingeniously manipulated to down-regulate the
      expression of any gene of interest, including VSRs, in artificial miRNA (amiRNA)
      based transgenics. Since we currently have a better understanding of the
      intricacies of miRNA-mediated gene regulation in plant-virus interactions, the
      majority of miRNAs manipulated to confer antiviral resistance to date are in
      plants. This review will share the insights gained from the studies of plant
      virus combat and from the endeavour to manipulate miRNAs, including prospective
      challenges in the context of the evolutionary dynamics of the viral genome. Next
      generation sequencing technologies and bioinformatics analysis will further
      delineate the molecular details of host-virus interactions. The need for
      appropriate environmental risk assessment principles specific to amiRNA-based
      virus resistance is also discussed.

PMID- 24445905
TI  - Metabolic basis of ethnic differences in diabetes risk in overweight and obese
      youth.
AB  - The global pandemic of childhood obesity has led to increased risk for
      prediabetes and type 2 diabetes mellitus (T2DM). Studies have shown decreased
      insulin sensitivity and/or secretion with increasing adiposity and consistently
      observed greater risk for T2DM in obese, non-Caucasian youth. In the current
      review we describe recent advances in understanding how obesity and metabolic
      status in children and adolescents confers various risk profiles for T2DM among
      Latinos, African Americans, Caucasians, Asians, and Native Americans. These
      possible determinants include ectopic fat distribution, adipose tissue
      inflammation and fibrosis, and elevated plasma levels of nonesterified free fatty
      acids. Future work should aim to elucidate the ethnic-specific pathophysiology of
      T2DM in order to develop and implement appropriate prevention and treatment
      strategies based on different ethnic profiles of diabetes risk. 

PMID- 24445906
TI  - Psychotomimetic effects at initiation of cannabis use are associated with
      cannabinoid receptor 1 (CNR1) variants in healthy students.

PMID- 24445908
TI  - Chiral [NaMnIIMnIII3] and [Na2MnII2MnIII6] clusters constructed by chiral
      multidentate Schiff-base ligands: synthesis, structures, CD spectra and magnetic
      properties.
AB  - Two pairs of novel enantiomerically chiral clusters R/S-[NaMn(II)Mn(III)3L3(MU3
      O)] (R/S-1) and R/S-[Na2Mn(II)2Mn(III)6L6(MU3-O)2] (R/S-2) have been obtained via
      the self-assembly of R/S-H2L Schiff base ligands and different auxiliary ligands
      (N3(-), dca(-)) with divalent manganese salt in an air-exposed methanol-ethanol
      solution. The structures of R/S-1 and R/S-2 were characterized by single-crystal
      X-ray diffraction analysis and powder X-ray diffraction. When the dicyanamide
      anion serves as an auxiliary ligand in the assembling reaction system, a pair of
      enantiomeric clusters R/S-[NaMn(II)Mn(III)3L3(MU3-O)] (R-1 and S-1) with a
      trigonal bipyramid configuration were obtained, while another pair of
      enantiomeric clusters R/S-[Na2Mn(II)2Mn(III)6L6(MU3-O)2] (R-2 and S-2) were
      formed in the case of the azide. Interestingly, the skeleton configuration of R/S
      2 can be described as a 3-fold EO-azide bridging double trigonal bipyramid of
      [NaMn(II)Mn(III)3L3(MU3-O)]2via Mn(II) vertices. Circular dichroism (CD) spectra
      demonstrated the enantiomeric nature of the two pairs of clusters. Detailed
      direct current (DC) magnetic susceptibility studies in the temperature range 2
      300 K suggested that R-1 and R-2 showed predominantly antiferromagnetic
      interactions between the manganese centers.

PMID- 24445907
TI  - Neurocognitive development in 22q11.2 deletion syndrome: comparison with youth
      having developmental delay and medical comorbidities.
AB  - The 22q11.2 deletion syndrome (22q11DS) presents with medical and
      neuropsychiatric manifestations including neurocognitive deficits. Quantitative
      neurobehavioral measures linked to brain circuitry can help elucidate genetic
      mechanisms contributing to deficits. To establish the neurocognitive profile and
      neurocognitive 'growth charts', we compared cross-sectionally 137 individuals
      with 22q11DS ages 8-21 to 439 demographically matched non-deleted individuals
      with developmental delay (DD) and medical comorbidities and 443 typically
      developing (TD) participants. We administered a computerized neurocognitive
      battery that measures performance accuracy and speed in executive, episodic
      memory, complex cognition, social cognition and sensorimotor domains. The
      accuracy performance profile of 22q11DS showed greater impairment than DD, who
      were impaired relative to TD. Deficits in 22q11DS were most pronounced for face
      memory and social cognition, followed by complex cognition. Performance speed was
      similar for 22q11DS and DD, but 22q11DS individuals were differentially slower in
      face memory and emotion identification. The growth chart, comparing
      neurocognitive age based on performance relative to chronological age, indicated
      that 22q11DS participants lagged behind both groups from the earliest age
      assessed. The lag ranged from less than 1 year to over 3 years depending on
      chronological age and neurocognitive domain. The greatest developmental lag
      across the age range was for social cognition and complex cognition, with the
      smallest for episodic memory and sensorimotor speed, where lags were similar to
      DD. The results suggest that 22q11.2 microdeletion confers specific vulnerability
      that may underlie brain circuitry associated with deficits in several
      neuropsychiatric disorders, and therefore help identify potential targets and
      developmental epochs optimal for intervention. 

PMID- 24445909
TI  - [Complications of hernia surgery].

PMID- 24445910
TI  - [Melanomas of the female genital tract: state of the art].
AB  - Melanoma of the female genital tract is a rare location (less than 2% of
      melanomas all sites combined). These cancers have a very poor prognosis, due to
      the delay in diagnosis. Vulvar location is about 1% of melanomas then the vaginal
      location, uterine and ovarian. There is no consensus to date regarding their
      care, due to the rarity of the lesions. Their treatment must however be based on
      the current data concerning gynaecological cancers as well as standard management
      of cutaneous melanoma. The treatment is often based on conservative surgery,
      because radical resection does not improve survival. For the vulva and vagina,
      reconstructive surgery is possible. Treatment is sometimes supplemented by
      chemotherapy or radiotherapy, which could improve local control. The interest in
      the use of targeted therapy in these locations is not well known because of their
      rarity, but the study of genes c-Kit and BRAF provides new prospects for
      treatment. The objective of this review is to describe and report the current
      state of knowledge about gynaecologic melanomas. 

PMID- 24445911
TI  - Recapitulating the urinary bladder--where are we heading?

PMID- 24445913
TI  - Prostate cancer: How to manage prostate cancer with lymph node metastases?

PMID- 24445912
TI  - Landmarks in BPH--from aetiology to medical and surgical management.
AB  - Clinicians treat the symptoms associated with BPH on a daily basis. Although BPH
      is nearly universal with age, not all men develop lower urinary tract symptoms.
      Over the past 100 years, several notable advances in the field of urology have
      not only improved our understanding of the aetiology and natural history of this
      common disease, but have also facilitated the development of therapeutics to
      effectively manage BPH-related symptoms. The high quality of modern-day
      diagnosis, as well as medical and surgical treatment for BPH, is a testimony to
      centuries of observation and decades of scientific research.

PMID- 24445914
TI  - Should we give metformin to all men with CRPC?

PMID- 24445915
TI  - Age of onset should guide germline mutation testing.

PMID- 24445916
TI  - PTPN2 attenuates T-cell lymphopenia-induced proliferation.
AB  - When the peripheral T-cell pool is depleted, T cells undergo homoeostatic
      expansion. This expansion is reliant on the recognition of self-antigens and/or
      cytokines, in particular interleukin-7. The T cell-intrinsic mechanisms that
      prevent excessive homoeostatic T-cell responses and consequent overt
      autoreactivity remain poorly defined. Here we show that protein tyrosine
      phosphatase N2 (PTPN2) is elevated in naive T cells leaving the thymus to
      restrict homoeostatic T-cell proliferation and prevent excess responses to self
      antigens in the periphery. PTPN2-deficient CD8(+) T cells undergo rapid
      lymphopenia-induced proliferation (LIP) when transferred into lymphopenic hosts
      and acquire the characteristics of antigen-experienced effector T cells. The
      enhanced LIP is attributed to elevated T-cell receptor-dependent, but not
      interleukin-7-dependent responses, results in a skewed T-cell receptor repertoire
      and the development of autoimmunity. Our results identify a major mechanism by
      which homoeostatic T-cell responses are tuned to prevent the development of
      autoimmune and inflammatory disorders. 

PMID- 24445917
TI  - Ralph V. McKinney, Jr. award in basic and clinical research for 2013.

PMID- 24445918
TI  - Comparative histomorphometric analysis of maxillary sinus augmentation with
      absorbable collagen membrane and osteoinductive replaceable bony window in
      rabbits.
AB  - PURPOSE: The aim of this animal study was to evaluate, through histomorphometric
      evaluation, bone regeneration in rabbit maxillary sinuses with absorbable
      collagen membranes and osteoinductive replaceable bony windows over bone grafts.
      MATERIALS AND METHODS: Bilateral sinus augmentation procedures were performed in
      16 adult male rabbits. The rabbits were randomly assigned to 4 groups of 4
      rabbits each. Rectangular replaceable bony windows were made with a piezoelectric
      thin saw insert. In control group, grafted beta-tricalcium phosphate (beta-TCP)
      was covered by absorbable collagen membranes. In experimental groups, beta-TCP
      was grafted and covered by replaceable bony windows. The rabbits were killed at
      1, 2, 4, and 8 weeks postoperatively. The augmented sinuses were stained with
      hematoxylin-eosin and Masson trichrome stains and examined, under light
      microscopy, for newly formed bone and soft tissue changes in the maxillary
      sinuses. RESULTS: Histologically, significantly higher and faster new bone
      formation was observed in the augmented sinuses of the experimental groups,
      receiving homologous replaceable bony windows than in those of the control group
      receiving collagen membranes. CONCLUSION: This study demonstrates that, for
      augmentation, the use of the homologous replaceable bony window over bone graft
      material on the maxillary sinus accelerates bone regeneration.

PMID- 24445919
TI  - Cellular response of calcium phosphate bone substitute containing hydroxyapatite
      and tricalcium phosphate.
AB  - PURPOSE: This study developed calcium phosphate bone substitutes and their
      microstucture and in vitro cell response were evaluated in comparison with
      commercial hydroxyapatite (HA). MATERIALS: HA powder was ball-milled and then
      sintered to transfer into the calcium phosphate bulks (CPB). The density,
      hardness, and microstructure of the CPB were investigated. The viability and
      proliferation of MG63 osteoblast-like cells on the commercial HA and the CPB were
      evaluated. RESULTS: The x-ray diffraction confirmed that the CPB consisted of
      alpha-tricalcium phosphate (alpha-TCP), CaO, and HA. The hardness, density, and
      alpha-TCP-to-HA ratio of the CPB decreased when increasing the sintering
      duration. Cell tests demonstrated that the CPB exhibited an earlier cell-spread
      response than the commercial HA. CONCLUSIONS: This study demonstrated that a
      phase transformation of HA into alpha-TCP and CaO was achieved by sintering. The
      cell tests indicated that the CPB has favorable in vitro cellular performance,
      which implied that it presented potential as bone substitute.

PMID- 24445920
TI  - Current state and perspectives of penicillin G acylase-based biocatalyses.
AB  - In the course of more than 60-year history, penicillin G acylase (PGA) gained a
      unique position among enzymes used by pharmaceutical industry for production of
      beta-lactam antibiotics. Kinetically controlled enzymatic syntheses of
      cephalosporins of novel generations in which PGA catalyzes coupling of activated
      acyl donor with nucleophile belong among the latest large-scale applications.
      Contrary to rather specific roles of other enzymes involved in beta-lactam
      biocatalyses, the PGA seems to have the greatest potential. On the laboratory
      scale, other applications with industrial potential were described, e.g.,
      directed evolution of the enzyme to meet specific demands of industrial processes
      or its modification into the enzyme catalyzing reactions with novel substrates.
      The fact that beta-lactams represent the most important group of antibiotics
      comprising 65 % of the world antibiotic market explains such a tremendous and
      continuous interest in this enzyme. Indeed, the annual consumption of PGA has
      recently been estimated to range from 10 to 30 million tons. The application
      potential of the enzyme goes beyond the beta-lactam biocatalysis due to its
      enantioselectivity and promiscuity: the PGA can be used for the production of
      achiral and chiral compounds convenient for the preparation of synthons and
      active pharmaceutical ingrediences, respectively. These biocatalyses, however,
      still wait for large-scale application.

PMID- 24445921
TI  - Construction and application of an expression vector from the new plasmid pLAtc1
      of Acidithiobacillus caldus.
AB  - In this study, a recently sequenced 9.8-kb plasmid, pLAtc1, from
      Acidithiobacillus caldus strain SM-1 was characterized and developed into an
      expression vector. The pLAtc1 backbone carried an oriV, three rep genes, five mob
      genes, a Nic site, and an addiction system. Multilocus sequence analysis
      indicated that pLAtc1 was phylogenetically more related to the IncQ-like broad
      host range plasmids than to other IncQ plasmids. pLAtc1 was able to replicate and
      reside in Gram-negative Escherichia coli, Comamonas testosteroni, but not in Gram
      positive Corynebacterium glutamicum. pLAtc1 was mobilized via conjugation into E.
      coli BL21 and A. caldus SM-1 from E. coli S17-1. Quantitative PCR revealed seven
      and four copies of plasmid in A. caldus and E. coli cells, respectively. The
      expression vector pLAtcE was constructed from pLAtc1 by introducing a regulatable
      promoter (P tetH ), a transcriptional terminator, a multiple cloning site, a
      kanamycin resistance gene, and a streptomycin resistance gene. The functionality
      of pLAtcE was demonstrated by expressing a gene encoding enhanced green
      fluorescence protein in E. coli and in A. caldus. pLAtcE was used to express
      alpha-ketoglutarate dehydrogenase (sucAB) and succinate dehydrogenase (sdhA)
      genes in A. caldus. The newly engineered strain that harbored sucAB and sdhA on a
      plasmid pLAtcE-sucA-sucB-sdhA grew better than the parent strain SM-1/pLAtcE in
      tetrathionate and glucose-supplemented medium and produced more acidity and
      resulted in a more oxidative environment. This study created a useful molecular
      tool for genetic manipulation of the thermoacidophilic and autotrophic A. caldus.

PMID- 24445922
TI  - Directed evolution of the CpcA biosynthetic pathway and optimization of
      conditions for CpcA production and its properties.
AB  - To improve the production of phycocyanin holo-alpha-subunit (CpcA) from Spirulina
      maxima, five genes and their spacer region sequences involved in its biosynthesis
      were subject to the directed evolution by error-prone PCR using the plasmid
      pETDuet-6 as the template. Mutants were screened by determining the CpcA yield in
      96-well plates directly. A mutant strain CPCA713 with the highest CpcA yield of
      17.36 mg/l in 96-well plates was obtained, and this yield was 29.7 % higher than
      that from the control strain ZJGSU09 containing pETDuet-6 (13.38 mg/l). Sequence
      alignments indicated that 10 nucleotides and 5 amino acids were mutated. Glycerol
      and beef extract were found to be the best carbon and nitrogen sources for
      accumulating CpcA in the screened CPCA713 strain, respectively. The
      concentrations of the key factors that affected the CpcA yield were optimized by
      response surface methodology with a Box-Behnken design and were as follows:
      glycerol, 16.0 g/l; yeast extract, 18.2 g/l; and beef extract, 4.8 g/l. Under the
      optimal conditions, the CpcA yield was up to 71.21 mg/l in the shake flask. Time
      course of the CpcA production before and after optimization were performed and
      compared. After being purified by a Hi-Trap metal chelating affinity column
      loaded with 100 mM nickel sulfate, CpcA presented a single protein band with an
      estimated molecular weight of 29 kDa in the sodium dodecyl sulfate polyacrylamide
      gel electrophoresis gel. The purified CpcA had the maximal absorptive and
      fluorescent emission wavelengths at 623 and 650.8 nm, respectively, and was
      stable at temperatures of 40  degrees C below and pHs of 5.5-8.0, and in the dark
      or in the dim light. It had also a strong scavenging ability to three free
      radicals .OH, .O2 (-), and di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH).
      The IC50 values of .OH, .O2 (-), and DPPH free radicals by purified CpcA were
      0.08, 0.46, and 0.48 mg/ml, respectively. This study lays a good foundation for
      the industrial production of CpcA by engineered Escherichia coli in future. 

PMID- 24445923
TI  - Exogenous surfactant attenuates lung injury from gastric-acid aspiration during
      ex vivo reconditioning in pigs.
AB  - BACKGROUND: Lung injury (LI) due to gastric-acid aspiration is associated with
      poor posttransplantation outcomes. We investigated the effects of ex vivo lung
      perfusion (EVLP) reconditioning and surfactant administration on LI due to
      gastric-acid aspiration. METHODS: Thirty piglets were allocated at random to five
      groups: the lungs were studied 24 hr after gastric juice-induced LI of the left
      lower lobe (LLL), LI followed by EVLP (4 hr), or LI followed by LLL surfactant
      lavage immediately before EVLP; sham animals were studied 24 hr after saline
      infusion alone or followed by EVLP. Gross anatomy, hemodynamics, and aerodynamics
      were evaluated; neutrophil and bacterial counts were determined in
      bronchoalveolar lavage (BAL) fluid and blood. LLLs were evaluated based on a semi
      quantitative histologic score, apoptotic cell death (TUNEL), and inflammatory
      cytokine levels. RESULTS: The sham and sham-EVLP groups were not significantly
      different. Compared with sham, LI animals had irreversible atelectasis, higher
      lung infection rates (P<0.0001) and BAL neutrophil percentages (P<0.0001), lower
      PaO2 (P=0.0006), higher IL-1 (P=0.022) and IL-8 (P=0.006), higher apoptotic cell
      percentages (P=0.007), and worse histologic severity scores (P<0.0001). EVLP
      alone did not improve these findings. Adding surfactant before EVLP returned
      PaO2, pulmonary vascular resistance, and apoptotic-cell percentage to sham-EVLP
      values but only partially improved the histologic severity score. CONCLUSION:
      Local surfactant infusion immediately before EVLP improved the function of donor
      lungs injured by gastric juice aspiration. This strategy may hold promise for
      decreasing the shortage of donor lungs.

PMID- 24445924
TI  - Comparative analysis of drug action on B-cell proliferation and differentiation
      for mycophenolic acid, everolimus, and prednisolone.
AB  - BACKGROUND: Although more attention has been paid recently to B-cell immunity,
      assay for B-cell analysis has yet to be clinically applicable because, unlike T
      cell, a B-cell culture system has not been well established. METHODS: We
      attempted to develop an in vitro culture system for the proliferation and
      differentiation of peripheral B cells into plasma cells, and to analyze the
      action of everolimus (EVR), mycophenolic acid (MPA), and prednisolone (PRD).
      RESULTS: Using a three-step culture system, peripheral CD19 B cells could
      differentiate into plasma cells and produce IgG antibody. Activated B cells
      (CD19(hi)CD38(lo)IgD(-)), plasmablasts (CD19(hi)CD38(hi)IgD(-)), and plasma cells
      (CD19(lo/-)CD38(hi)IgD(-)) were observed as a main cell subset in step 1 (day 0
      4), 2 (day 4-7), and 3 (day 7-10), respectively. IgG production on day 10 was
      significantly suppressed by EVR, MPA, and PRD, but not cyclosporine. Although
      both EVR and MPA inhibited B-cell proliferation and differentiation in step 1,
      EVR suppressed B-cell differentiation in step 2. Only a high concentration of PRD
      significantly inhibited B-cell proliferation, differentiation, and IgG production
      in step 3. CONCLUSIONS: Although both MPA and EVR efficiently suppressed cell
      proliferation during the early phase of B-cell immune reaction, EVR could act in
      a later phase than MPA. PRD at a high concentration worked even in the last
      phase. An in vitro B-cell culture system would clarify the mode of drug action
      during B-cell differentiation and provide useful information on the effective
      selection or combination of immunosuppressive agents.

PMID- 24445925
TI  - A human-specific mutation limits nonhuman primate efficacy in preclinical
      xenotransplantation studies.
AB  - BACKGROUND: Patients diagnosed with fulminant hepatic failure face high mortality
      rates. A potential therapeutic approach for these patients is the use of
      extracorporeal porcine liver perfusion, to serve as a form of "liver dialysis."
      Previously, our laboratory has shown that, during a 72-hour extracorporeal
      perfusion with human blood, porcine Kupffer cells bind to and phagocytose human
      erythrocytes causing the hematocrit to fall to 2.5% of the original value.
      Subsequently, erythrocyte binding has been shown to involve N-acetylneuraminic
      acid (Neu5Ac) on the surface of human erythrocytes and sialoadhesin on the
      surface of the porcine Kupffer cells. METHODS: Given that no primate other than
      the human is known to express the majority of its sialic acid as Neu5Ac, we
      evaluated whether nonhuman primates would provide adequate evaluation of the loss
      of erythrocytes that might be expected in a clinical trial of extracorporeal
      porcine liver perfusion. RESULTS: We found that while porcine macrophages readily
      bound human erythrocytes, binding of nonhuman primate erythrocytes was
      significantly reduced (P<0.001). CONCLUSIONS: This study suggests that nonhuman
      primates may fail to serve as an adequate model for studying extracorporeal
      porcine liver perfusion because of the fact that porcine macrophages do not bind
      nonhuman primate erythrocytes.

PMID- 24445926
TI  - Graft failure due to noncompliance among 628 kidney transplant recipients with
      long-term follow-up: a single-center observational study.
AB  - BACKGROUND: In adult kidney transplantation, there is no clear consensus on the
      incidence of graft failure-due-to noncompliance (GFNC), with some reporting it as
      relatively uncommon and others as a major cause of late graft failure. We
      suspected that GFNC was a major cause of late graft loss at our center but did
      not know the extent of this problem. METHODS: In our prospectively followed
      cohort of 628 adult, primary kidney-alone transplant recipients with long-term
      follow-up, GFNC and other graft loss causes were determined from our ongoing
      clinical evaluations. Using competing risks methodology, we determined the
      overall percentage of patients developing GFNC and the significant prognostic
      factors for its hazard rate and cumulative incidence (via Cox regression).
      RESULTS: Cumulative incidence estimates (+/- standard error) of GFNC (n=29), GF
      with-compliance (n=46), receiving a never-functioning graft (n=7), and death-with
      a-functioning-graft (n=53) at 101 months after transplant (last-observed-graft
      loss) were as follows: 9.8%+/- 2.4%, 10.9%+/- 1.7%, 1.1%+/- 0.4%, and 13.0%+/-
      1.9%, respectively. Only three patients experienced GFNC during the first 24
      months; GFNC represented 48.1% (26/54) of death-censored GFs beyond 24 months.
      Two baseline variables were jointly associated with a significantly higher GFNC
      hazard and cumulative incidence: younger recipient age (P<0.000001 each) and non
      white recipient (P=0.004 and P=0.02). Estimated percentages of ever developing
      GFNC were 28.4%+/- 6.5% among 79 non-whites younger than 35 years versus 0.0%
      (0/144) among whites 50 years or older. Among 302 recipients younger than 50
      years, 18.1%+/- 4.1% developed GFNC, representing 67.6% (25/37) of its death
      censored graft failures observed beyond 24 months after transplant. CONCLUSIONS:
      GFNC is a major cause of late GF at our center, with younger and non-white
      recipients at a significantly greater GFNC risk. Interventional approaches to
      eliminate GFNC could dramatically improve long-term kidney graft survival.

PMID- 24445928
TI  - Metastasis of e-mail at an academic medical center.

PMID- 24445927
TI  - Pre-seizure state identified by diffuse optical tomography.
AB  - In epilepsy it has been challenging to detect early changes in brain activity
      that occurs prior to seizure onset and to map their origin and evolution for
      possible intervention. Here we demonstrate using a rat model of generalized
      epilepsy that diffuse optical tomography (DOT) provides a unique functional
      neuroimaging modality for noninvasively and continuously tracking such brain
      activities with high spatiotemporal resolution. We detected early hemodynamic
      responses with heterogeneous patterns, along with intracranial
      electroencephalogram gamma power changes, several minutes preceding the
      electroencephalographic seizure onset, supporting the presence of a "pre-seizure"
      state. We also observed the decoupling between local hemodynamic and neural
      activities. We found widespread hemodynamic changes evolving from local regions
      of the bilateral cortex and thalamus to the entire brain, indicating that the
      onset of generalized seizures may originate locally rather than diffusely.
      Together, these findings suggest DOT represents a powerful tool for mapping early
      seizure onset and propagation pathways. 

PMID- 24445929
TI  - Applications to restrict elderly people without mental capacity rose 70% in three
      years.

PMID- 24445930
TI  - In situ sensing of subsurface contamination--part I: near-infrared spectral
      characterization of alkanes, aromatics, and chlorinated hydrocarbons.
AB  - There is an imperative need for a chemical sensor capable of remote, in situ,
      long-term monitoring of chemical species at sites containing toxic chemical
      spills, specifically at chemical waste dumps, landfills, and locations with
      underground storage tanks. In the current research, a series of experiments were
      conducted measuring the near-infrared optical absorption of alkanes, aromatics,
      and chlorinated hydrocarbons. A spectral library was then developed to
      characterize the optical spectra of liquid hydrocarbons. Near-infrared analysis
      was chosen due to compatibility with optical fibers. The goal was to
      differentiate between classes of hydrocarbons and to also discriminate between
      compounds within a class of similar molecular structures. It was observed that
      unique absorption spectra can be obtained for each hydrocarbon, and this
      uniqueness can be used to discriminate between hydrocarbons from different
      families. Statistical analyses, namely, principal component analysis (PCA) and
      correlation coefficient (Spearman and Pearson methods), were attempted to match
      absorption spectra from an unknown hydrocarbon with the database with limited
      success. An algorithm was subsequently written to identify the characteristic
      peaks of each hydrocarbon that could be used to match data from an unknown
      chemical species with the database. 

PMID- 24445931
TI  - Biosorption of antimony(V) by freshwater cyanobacteria Microcystis from Lake
      Taihu, China: effects of pH and competitive ions.
AB  - There is limited knowledge available on metalloid biosorption by freshwater
      algae. In this study, biosorption properties of anionic Sb(OH) 6 (-) by naturally
      occurring cyanobacteria Microcystis were investigated as a function of initial
      pH, biosorbent dosage, contact time, and addition sequences of competitive ions,
      and their binding mechanisms were discussed. The biosorption process was fast and
      equilibrium was reached at 2 h. Sb(V) biosorption decreased with the increase of
      pH and the optimum pH range was 2.5-3.0, which corresponded with the changes of
      surface charges of the cell wall of Microcystis. The biosorption data
      satisfactorily followed the Freundlich model. The simultaneous addition of H2PO4
      (-) and Ca(2+) enhanced Sb(V) biosorption, while NO3 (-) greatly inhibited the
      biosorption, compared with single Sb(V) addition. The initial addition of the
      competitive ions reduced Sb(V) biosorption at higher Sb(V) concentrations,
      compared with simultaneous addition. A fraction of biosorbed Sb(V) was replaced
      by the competitive ions which were added subsequently, and the exchange only
      occurred at higher concentrations of Sb(V). 1.0 mol/L HCl demonstrated the
      highest desorption efficiency. Speciation analyses indicated that no reduction of
      Sb(V) into Sb(III) occurred. Based on the results of zeta potential and
      attenuated total reflection infrared spectroscopy spectra, Sb(OH) 6 (-) bound to
      the biomass through electrostatic attraction and surface complexation, and amino,
      carboxyl, and hydroxyl groups were involved in the biosorption process. The study
      suggest that Microcystis from cyanobacteria blooms could be used as a potential
      biosorbent to remove Sb(V) from effluents at environmentally relevant
      concentrations (<=10.0 mg/L). 

PMID- 24445933
TI  - Hydrosilylation catalysis by an earth alkaline metal silyl: synthesis,
      characterization, and reactivity of bis(triphenylsilyl)calcium.
AB  - Bis(triphenylsilyl)calcium [Ca(SiPh3)2(thf)] obtained in high yield as a
      crystalline ether adduct catalyzes the hydrosilylation of activated C-C double
      bonds efficiently and regioselectively. 

PMID- 24445932
TI  - Biological effects of ammonia released from a composting plant assessed with
      lichens.
AB  - In this study, we investigated whether ammonia emissions from industrial
      composting of organic waste may influence the surrounding environment, using
      lichens as bioindicators. To this purpose, samples of N-tolerant and N-sensitive
      lichens, namely Xanthoria parietina and Evernia prunastri, were transplanted for
      1-3 months along transects at increasing distance (0-400 m) from a composting
      facility in Tuscany, Italy. Atmospheric concentrations of ammonia were measured
      using passive samplers. The physiological response of lichen transplants was
      investigated by means of the photosynthetic efficiency (measured as chlorophyll a
      fluorescence emission), the integrity of cell membranes (measured as electrolyte
      leakage), and sample viability (measured as enzymatic activity of dehydrogenase).
      Epiphytic lichen communities were investigated using biodiversity indices. The
      results showed decreasing concentrations of ammonia, from 48.7 MUg/m(3) at the
      composting facility to 2.7 MUg/m(3) at 400 m. The N-tolerant X. parietina was not
      affected and some physiological parameters even showed a higher performance,
      while the N-sensitive E. prunastri showed a reduced performance with increasing
      atmospheric concentrations approaching the source. A shift from lichen
      communities composed by meso-acidophilous species (actual condition) to more
      nitrophilous communities in the near future, approaching the composting facility
      is suggested. It is concluded that lichens can provide useful data for decision
      makers to establish correct science-based environmentally sustainable waste
      management policies. 

PMID- 24445934
TI  - Letter from the editors.

PMID- 24445935
TI  - Expression of ZNF396 in basal cell carcinoma.
AB  - Zfp191 represses differentiation and keeps various cells in the stem/progenitor
      stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in
      basal cell carcinoma (BCC) and possibly represses the expression of a Notch
      system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC
      cells from undergoing Notch-mediated squamous cell differentiation. ZNF396
      immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74
      squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues,
      ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing
      of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC
      cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited
      the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress
      Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous
      differentiation in BCC. 

PMID- 24445936
TI  - Atrial fibrillation in heart failure: stroke risk stratification and
      anticoagulation.
AB  - For an individual patient with both atrial fibrillation and heart failure, stroke
      risk is one of the most prominent mitigating factors for subsequent morbidity and
      mortality. Although the CHADS2 stroke risk score is the most widely used score
      for risk stratification, it does not take into account the risk factors of
      vascular disease, female gender, or the age group 65-74 years, for which there is
      increasing evidence. There is also evidence that diastolic heart failure is as
      much a risk factor for stroke as systolic heart failure. The new oral
      anticoagulants dabigatran, rivaroxaban and apixaban appear to be appropriate
      agents in the heart failure population with atrial fibrillation and risk factors
      for stroke although there are dose-adjustments for renal insufficiency and these
      medications are contraindicated in advanced renal disease. As with the atrial
      fibrillation population as a whole, bleeding risk should be considered for every
      patient with heart failure prior to making recommendations regarding
      anticoagulation.

PMID- 24445937
TI  - MicroRNA-29b inhibits diabetic nephropathy in db/db mice.
AB  - Inflammation and its consequent fibrosis are two main features of diabetic
      nephropathy (DN), but target therapy on these processes for DN remains yet
      ineffective. We report here that miR-29b is a novel therapeutic agent capable of
      inhibiting progressive renal inflammation and fibrosis in type 2 diabetes in
      db/db mice. Under diabetic conditions, miR-29b was largely downregulated in
      response to advanced glycation end (AGE) product, which was associated with
      upregulation of collagen matrix in mesangial cells via the transforming growth
      factor-beta (TGF-beta)/Smad3-dependent mechanism. These pathological changes were
      reversed by overexpressing miR-29b, but enhanced by knocking-down miR-29b.
      Similarly, loss of renal miR-29b was associated with progressive diabetic kidney
      injury, including microalbuminuria, renal fibrosis, and inflammation. Restored
      renal miR-29b by the ultrasound-based gene therapy was capable of attenuating
      diabetic kidney disease. Further studies revealed that inhibition of Sp1
      expression, TGF-beta/Smad3-dependent renal fibrosis, NF-kappaB-driven renal
      inflammation, and T-bet/Th1-mediated immune response may be mechanisms associated
      with miR-29b treatment in db/db mice. In conclusion, miR-29b may play a
      protective role in diabetic kidney disease and may have therapeutic potential for
      diabetic kidney complication. 

PMID- 24445939
TI  - [Circulating tumor cells: liquid biopsy].
AB  - The detection and molecular characterization of circulating tumor cells (CTCs)
      are one of the most active areas of translational cancer research, with more than
      400 clinical studies having included CTCs as a biomarker. The aims of research on
      CTCs include: a) estimation of the risk for metastatic relapse or metastatic
      progression (prognostic information); b) stratification and real-time monitoring
      of therapies; c) identification of therapeutic targets and resistance mechanisms;
      and d) understanding metastasis development in cancer patients. This review
      focuses on the technologies used for the enrichment and detection of CTCs. We
      outline and discuss the current technologies that are based on exploiting the
      physical and biological properties of CTCs. A number of innovative technologies
      to improve methods for CTC detection have recently been developed, including CTC
      microchips, filtration devices, quantitative reverse-transcription PCR assays,
      and automated microscopy systems. Molecular characterization studies have
      indicated, however, that CTCs are very heterogeneous, a finding that underscores
      the need for multiplex approaches to capture all of the relevant CTC subsets. We
      therefore emphasize the current challenges of increasing the yield and detection
      of CTCs that have undergone an epithelial-mesenchymal transition. Increasing
      assay analytical sensitivity may lead, however, to a decrease in analytical
      specificity (e.g., through the detection of circulating normal epithelial cells).
      A considerable number of promising CTC detection techniques have been developed
      in recent years. The analytical specificity and clinical utility of these methods
      must be demonstrated in large prospective multicenter studies to reach the high
      level of evidence required for their introduction into clinical practice. 

PMID- 24445938
TI  - In vivo proof of concept of adoptive immunotherapy for hepatocellular carcinoma
      using allogeneic suicide gene-modified killer cells.
AB  - Cell therapy based on alloreactivity has completed clinical proof of concept
      against hematological malignancies. However, the efficacy of alloreactivity as a
      therapeutic approach to treat solid tumors is unknown. Using cell culture and
      animal models, we aimed to investigate the efficacy and safety of allogeneic
      suicide gene-modified killer cells as a cell-based therapy for hepatocellular
      carcinoma (HCC), for which treatment options are limited. Allogeneic killer cells
      from healthy donors were isolated, expanded, and phenotypically characterized.
      Antitumor cytotoxic activity and safety were studied using a panel of human or
      murine HCC cell lines engrafted in immunodeficient or immunocompetent mouse
      models. Human allogeneic suicide gene-modified killer cells (aSGMKCs) exhibit a
      high, rapid, interleukin-2-dependent, and non-major histocompatibility complex
      class I-restricted in vitro cytotoxicity toward human hepatoma cells, mainly
      mediated by natural killer (NK) and NK-like T cells. In vivo evaluation of this
      cell therapy product demonstrates a marked, rapid, and sustained regression of
      HCC. Preferential liver homing of effector cells contributed to its marked
      efficacy. Calcineurin inhibitors allowed preventing rejection of allogeneic
      lymphocytes by the host immune system without impairing their antitumor activity.
      Our results demonstrate proof of concept for aSGMKCs as immunotherapy for HCC and
      open perspectives for the clinical development of this approach. 

PMID- 24445940
TI  - [Infections in dermatology].

PMID- 24445941
TI  - [Persistent and recurrent skin and soft tissue infections by Staphylococcus
      aureus. Impact of the small colony-variant (SCV) phenotype and of Panton
      Valentine leukocidin (PVL)-positive S. aureus isolates].
AB  - Staphylococcus aureus is one of the major pathogens causing chronic skin and soft
      tissue infections. Particularly isolates producing Panton-Valentine leukocidin
      (PVL) comprising methicillin-susceptible and community-associated methicillin
      resistant S. aureus (CA-MRSA) have been associated with more aggressive and
      persistent or relapsing courses. Beyond classical resistance mechanisms,
      functional resistance as shown by the small colony-variant (SCV) phenotype could
      be also responsible for treatment failures, despite the administration of
      antibiotics tested in vitro as susceptible. Also this phenotype has been
      associated with chronic courses of infections often with multiple exacerbations.
      Due to their ability to persist intracellularly, SCVs are protected from host
      defense and antibiotic treatment if only extracellularly active agents are
      administered. Reduced growth, abnormal colony morphology and changes in the
      metabolism of the SCVs aggravate drastically their identification,
      differentiation and susceptibility testing. The diagnostic and therapeutic
      challenges of PVL-positive and SCV isolates necessitate close collaboration with
      microbiological and infectious disease specialists. 

PMID- 24445942
TI  - [Significance and prevention of post-operative wound complications].
AB  - Although surgical site infections (SSI) in dermatologic operative procedures are
      extremely rare, it is important to understand risks and etiological factors to
      initiate risk assessment and specific preventive measures. SSI commonly are
      associated with a complicated, long-term and expensive outcome. Typical wound
      pathogens of these infections include a variety of multiresistant organisms along
      with Staphylococcus aureus, Staphylococcus epidermidis, hemolytic streptococci
      and the gram-negative bacilli Escherichia coli and Pseudomonas aeruginosa.
      Effective hygienic measures as part of an adequate quality management system
      should consider the critical points in the development of SSI, particularly in
      the setting of an outpatient dermatologic unit, such as preparation of the
      operative area, preoperative skin antisepsis, hand hygiene, safe and skilled
      technique by surgeons, and barrier nursing to prevent spread of pathogens. The
      baseline infection incidence in dermatologic surgery inherently is low;
      nevertheless significant improvements can be achieved by implementation of risk
      adapted infection control measures. 

PMID- 24445944
TI  - [The skin's own antibiotics. Important features of antimicrobial peptides for
      clinical practice].
AB  - Despite permanent confrontation with a potentially harmful environment, its own
      microbiota and the fact that minor injuries occur frequently in everyday life,
      skin infections are a rare event. A chemical barrier of antimicrobial peptides
      (AMP), some of them constitutively expressed, others inducible by various
      stimuli, contributes to the integument's resistance. AMP are evolutionarily old
      components of the innate immunity which became the focus of interest due to their
      broad spectrum of activity against microorganisms and the rare occurrence of
      antimicrobial resistance. These attributes make them promising alternative
      candidates for future antibiotics. Furthermore various dermatological diseases
      are associated with an altered expression of these molecules, which might then
      play a pathogenetic role. In addition to their antimicrobial activity, some AMP
      have immunomodulatory effects and can promote wound healing, properties which
      currently are under intensive research. 

PMID- 24445943
TI  - [Microbial stress of skin and wounds in clinical aspects and practice. Between
      search and destroy and monitor and relax].
AB  - The antibiotic treatment of microbial pathogens of the skin and wounds could so
      far not fulfil the expectations of an effective and permanent elimination of
      pathogens so that local treatment with antiseptic agents as a flanking measure to
      wound cleansing and debridement has become increasingly more established. Because
      an antiseptic treatment does not actually represent a treatment of infections,
      the current antimicrobial treatment strategy for infections in skin and wound
      areas consists of combined antibiotic and flanking antiseptic administration
      following debridement. However, the combined therapy is not always successful.
      There is an urgent need for new forms of therapy particularly to combat
      multiresistant pathogens in biofilms in infections of chronic and other
      complicated wounds. 

PMID- 24445945
TI  - [Secondary generalized brachioradial pruritus. An uncommon but easy-to-use
      differential diagnostic approach to generalized pruritus].
AB  - Brachioradial pruritus is a neuropathic form of chronic pruritus and mostly
      localized on the forearms. We report on a patient whose pruritus generalized 4
      months after beginning on the forearms. The mechanism that leads to
      generalization is still unknown; multiplier factors may be involved. Systemic
      therapy with anticonvulsants and physical therapy measures produced improvement.
      This form of pruritus requires a focused, interdisciplinary diagnostic approach
      and therapy. 

PMID- 24445946
TI  - [Basic or maintenance therapy in dermatology. Appropriate vehicles, possibilities
      and limitations].
AB  - Topical therapy of dermatological diseases includes treatment with active
      ingredients in combination with basic or maintenance therapy. An appropriate
      basic therapy can be used as prophylaxis to avoid or decrease occurrence of
      disease episodes and therefore counteract chronic disease manifestations. Long
      term basic therapy is suitable especially for chronic dermatoses to prevent the
      onset of symptoms. This also makes basic therapy a type of preventive therapy. At
      the same time, adequate basic therapy leads to an increased quality of life,
      which is often considerably reduced in patients with a chronic dermatologic
      disease. Choosing the right vehicle for basic therapy is an important criterion
      along with the choice of appropriate active ingredients for successful treatment.
      This should be done using established standard vehicles recommended in the
      various pharmacopeia. 

PMID- 24445947
TI  - One-pot synthesis of iron doped mesoporous silica catalyst for propane
      ammoxidation.
AB  - Iron doped hexagonal mesoporous silica (Fe-HMS) was successfully prepared by one
      pot direct synthesis at ambient temperature by using dodecylamine as a templating
      agent. The catalyst has been characterized by various techniques including XRD,
      DR-UV-Vis, FTIR, SEM and N2 adsorption. The obtained material exhibits very large
      surface area (above 1000 m(2) g(-1)), mesoporosity with narrow distribution of
      pores (around 4 nm) and nano-crystallites with the 20-30 nm in size. The
      concentration of iron in the catalyst was 0.95 wt%. The prepared material was
      tested in the direct ammoxidation of propane. It was shown that direct synthesis
      leads to better dispersion of the metal compared to the material prepared by
      impregnation of pure HMS silica. It is also demonstrated that this material is
      able to catalyze the direct ammoxidation of propane and shows quite high
      selectivity to acrylonitrile (52% at 11% conversion of propane). 

PMID- 24445948
TI  - The effect of testosterone replacement therapy on prostate cancer: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Testosterone replacement therapy (TRT) is a widely accepted form of
      treatment worldwide for aging men with late-onset hypogonadism syndrome.
      Urologists have been concerned about the possibility of TRT causing prostate
      cancer. The aim of this study was to assess the relationship between TRT and
      prostate cancer. METHODS: A literature review was performed to identify all
      published, randomized controlled trials (RCTs) of testosterone treatment for
      hypogonadism. The search included the MEDLINE, Embase and the Cochrane Controlled
      Trials Register databases. Fixed-effect model was chosen for homogeneous studies;
      otherwise, a random-effect model was used. Inconsistency was quantified by using
      the I2 statistic, which tests the proportion of heterogeneity across studies.
      RESULTS: Results of 22 RCTs involving a total of 2351 patients were analyzed.
      Eleven RCTs were short-term (<12 months) and 11 were long-term (12-36 months)
      comparisons of TRT with a placebo; TRT was administered transdermally, orally or
      by injection. Respective odds ratio (OR) and 95% confidence interval (CI) values
      for injection, transdermal administration and oral administration of short-term
      TRT were as follows: prostate cancer: 0.39 (0.06-2.45), 1.10 (0.26-4.65) and no
      oral; biopsy: 5.28 (0.24-113.87), 2.11 (0.32-13.73) and no oral; and prostate
      nodule: 1.01 (0.13-7.60), no injection and oral. Respective OR and 95% CI values
      for injection, transdermal administration and oral administration of long-term
      TRT were as follows: prostate cancer: 2.09 (0.18-24.73), 3.06 (0.12-76.70) and
      0.19 (0.01-4.03); biopsy: 2.09 (0.18-24.73), 3.65 (0.88-15.20) and 0.97 (0.13
      7.03); and prostate nodule: 3.13 (0.12-80.68), 1.00 (0.06-16.41) and 0.97 (0.13
      7.03). Though for some routes of administration and some end points, the OR
      associated with testosterone administration were >1 indicating increased risk,
      none of these reached or even approached statistical significance (all P>0.10),
      which was consistent with the results of subgroup analyses and sensitivity
      analysis. Besides, sensitivity analysis indicated that short-term TRT was more
      likely to increase PSA levels than treatment with placebo (P<0.00001).
      CONCLUSIONS: This meta-analysis shows that regardless of the administration
      method, TRT is the short-term safety and does not promote prostate cancer
      development or progression but long-term data are warranted with justifiable end
      points.

PMID- 24445949
TI  - Quantum computing on encrypted data.
AB  - The ability to perform computations on encrypted data is a powerful tool for
      protecting privacy. Recently, protocols to achieve this on classical computing
      systems have been found. Here, we present an efficient solution to the quantum
      analogue of this problem that enables arbitrary quantum computations to be
      carried out on encrypted quantum data. We prove that an untrusted server can
      implement a universal set of quantum gates on encrypted quantum bits (qubits)
      without learning any information about the inputs, while the client, knowing the
      decryption key, can easily decrypt the results of the computation. We
      experimentally demonstrate, using single photons and linear optics, the
      encryption and decryption scheme on a set of gates sufficient for arbitrary
      quantum computations. As our protocol requires few extra resources compared with
      other schemes it can be easily incorporated into the design of future quantum
      servers. These results will play a key role in enabling the development of secure
      distributed quantum systems. 

PMID- 24445950
TI  - PAS kinase is a nutrient and energy sensor in hypothalamic areas required for the
      normal function of AMPK and mTOR/S6K1.
AB  - The complications caused by overweight, obesity and type 2 diabetes are one of
      the main problems that increase morbidity and mortality in developed countries.
      Hypothalamic metabolic sensors play an important role in the control of feeding
      and energy homeostasis. PAS kinase (PASK) is a nutrient sensor proposed as a
      regulator of glucose metabolism and cellular energy. The role of PASK might be
      similar to other known metabolic sensors, such as AMP-activated protein kinase
      (AMPK) and the mammalian target of rapamycin (mTOR). PASK-deficient mice resist
      diet-induced obesity. We have recently reported that AMPK and mTOR/S6K1 pathways
      are regulated in the ventromedial and lateral hypothalamus in response to
      nutritional states, being modulated by anorexigenic glucagon-like peptide-1 (GLP
      1)/exendin-4 in lean and obese rats. We identified PASK in hypothalamic areas,
      and its expression was regulated under fasting/re-feeding conditions and
      modulated by exendin-4. Furthermore, PASK-deficient mice have an impaired
      activation response of AMPK and mTOR/S6K1 pathways. Thus, hypothalamic AMPK and
      S6K1 were highly activated under fasted/re-fed conditions. Additionally, in this
      study, we have observed that the exendin-4 regulatory effect in the activity of
      metabolic sensors was lost in PASK-deficient mice, and the anorexigenic
      properties of exendin-4 were significantly reduced, suggesting that PASK could be
      a mediator in the GLP-1 signalling pathway. Our data indicated that the PASK
      function could be critical for preserving the nutrient effect on AMPK and
      mTOR/S6K1 pathways and maintain the regulatory role of exendin-4 in food intake.
      Some of the antidiabetogenic effects of exendin-4 might be modulated through
      these processes.

PMID- 24445953
TI  - On robust methodologies for managing public health care systems.
AB  - Authors focus on ontology-based multidimensional data warehousing and mining
      methodologies, addressing various issues on organizing, reporting and documenting
      diabetic cases and their associated ailments, including causalities. Map and
      other diagnostic data views, depicting similarity and comparison of attributes,
      extracted from warehouses, are used for understanding the ailments, based on
      gender, age, geography, food-habits and other hereditary event attributes. In
      addition to rigor on data mining and visualization, an added focus is on values
      of interpretation of data views, from processed full-bodied diagnosis, subsequent
      prescription and appropriate medications. The proposed methodology, is a robust
      back-end application, for web-based patient-doctor consultations and e-Health
      care management systems through which, billions of dollars spent on medical
      services, can be saved, in addition to improving quality of life and average life
      span of a person. Government health departments and agencies, private and
      government medical practitioners including social welfare organizations are
      typical users of these systems. 

PMID- 24445952
TI  - Inflammation and programmed cell death in Alzheimer's disease: comparison of the
      central nervous system and peripheral blood.
AB  - Although the central nervous system (CNS) has been defined as a privileged site
      in Alzheimer's disease (AD), periphery can be more than simply witness of events
      leading to neurodegeneration. The CNS and peripheral blood can mutually
      communicate through cells and factors trafficking from the circulation into the
      brain and vice versa. A number of articles have reviewed inflammatory profiles
      and programmed cell death (PCD) in AD, separately in the CNS and at the
      peripheral level. This review does not provide an exhaustive account of what has
      been published on inflammation and PCD in AD. Rather, the aim of this review is
      to focus on possible linkages between the central and the peripheral compartments
      during AD progression, by critically analyzing, in a comparative manner,
      phenomena occurring in the CNS as well as the peripheral blood. In fact, growing
      evidence suggests that CNS and peripheral inflammation might present common
      features in the disease. Microarrays and metabolomics revealed that dysfunction
      of the glycolytic and oxidative pathways is similar in the brain and in the
      periphery. Moreover, dysregulated autophagosome/lysosomal molecular machinery,
      both at the CNS and the peripheral level, in AD-related cell damage, has been
      observed. Possible implications of these observations have been discussed. 

PMID- 24445951
TI  - Cocaine-induced changes in NMDA receptor signaling.
AB  - Addictive states are often thought to rely on lasting modification of signaling
      at relevant synapses. A long-standing theory posits that activity at N-methyl-D
      aspartate receptors (NMDARs) is a critical component of long-term synaptic
      plasticity in many brain areas. Indeed, NMDAR signaling has been found to play a
      role in the etiology of addictive states, in particular, following cocaine
      exposure. However, no consensus is apparent with respect to the specific effects
      of cocaine exposure on NMDARs. Part of the difficulty lies in the fact that
      NMDARs interact extensively with multiple membrane proteins and intracellular
      signaling cascades. This allows for highly heterogeneous patterns of NMDAR
      regulation by cocaine in distinct brain regions and at distinct synapses. The
      picture is further complicated by findings that cocaine effects on NMDARs are
      sensitive to the behavioral history of cocaine exposure such as the mode of
      cocaine administration. This review provides a summary of evidence for cocaine
      induced changes in NMDAR expression, cocaine-induced alterations in NMDAR
      function, and cocaine effects on NMDAR control of intracellular signaling
      cascades. 

PMID- 24445954
TI  - Characterizing and controlling the inflammatory network during influenza A virus
      infection.
AB  - To gain insights into the pathogenesis of influenza A virus (IAV) infections,
      this study focused on characterizing the inflammatory network and identifying key
      proteins by combining high-throughput data and computational techniques. We
      constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1
      infections through integrating high-throughput data. We demonstrated that better
      discrimination between normal and inflammatory networks by network entropy than
      by other topological metrics. Moreover, we identified different dynamical
      interactions among TLR2, IL-1beta, IL10 and NFkappaB between normal and
      inflammatory networks using optimization algorithm. In particular, good
      robustness and multistability of inflammatory sub-networks were discovered.
      Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play
      important roles in controlling inflammation, and demonstrated that changes in
      network entropy of this complex negatively correlated to those of three proteins:
      TNFalpha, NFkappaB and COX-2. These findings provide significant hypotheses for
      further exploring the molecular mechanisms of infectious diseases and developing
      control strategies. 

PMID- 24445955
TI  - Effects of caffeine on intermittent hypoxia in infants born prematurely: a
      randomized clinical trial.
AB  - IMPORTANCE: Preterm infants have immature respiratory control and resulting
      intermittent hypoxia (IH). The extent of IH after stopping routine caffeine
      treatment and the potential for reducing IH with extended caffeine treatment are
      unknown. OBJECTIVES: To determine (1) the frequency of IH in premature infants
      after discontinuation of routine caffeine treatment and (2) whether extending
      caffeine treatment to 40 weeks' postmenstrual age (PMA) reduces IH. DESIGN,
      SETTING, AND PARTICIPANTS: A prospective randomized clinical study was conducted
      at 16 neonatal intensive care units in the United States, with an 18-month
      enrollment period. Preterm infants (<32 weeks' gestation) previously treated with
      caffeine were randomized to extended caffeine treatment or usual care (controls)
      at a PMA of at least 34 weeks but less than 37 weeks. Continuous pulse oximeter
      recordings were obtained through 40 weeks' PMA. Oximeter data were analyzed by
      persons masked to patient group. INTERVENTION: Continued treatment with caffeine.
      MAIN OUTCOMES AND MEASURES: Number of IH events and seconds with less than 90%
      hemoglobin oxygen saturation (Sao2) per hour of recording. RESULTS: Our analysis
      included 95 preterm infants. In control infants, the mean (SD) time at less than
      90% Sao2 at 35 and 36 weeks' PMA was 106.3 (89.0) and 100.1 (114.6) s/h,
      respectively. The number of IH events decreased significantly from 35 to 39
      weeks' PMA (P = .01). Extended caffeine treatment reduced the mean time at less
      than 90% Sao2 by 47% (95% CI, -65% to -20%) to 50.9 (48.1) s/h at 35 weeks and by
      45% (95% CI, -74% to -17%) to 49.5 (52.1) s/h at 36 weeks. CONCLUSIONS AND
      RELEVANCE: Substantial IH persists after discontinuation of routine caffeine
      treatment and progressively decreases with increasing PMA. Extended caffeine
      treatment decreases IH in premature infants. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01875159.

PMID- 24445956
TI  - Atypical vertebral Paget's disease.
AB  - A 40-year-old Mauritanian man consulted for back pain. A computed tomography of
      the spine showed patchy sclerosis of the fifth and seventh thoracic vertebral
      bodies with normal neural arch of T5 and sclerosis and hypertrophy of the neural
      arch of T7, as well as diffuse sclerosis of the T11 vertebral body with a normal
      neural arch. At MRI, low signal-intensity on T1-weighted images and high signal
      intensity on T2-weighted images involved the whole T5 and T7 vertebrae and the
      vertebral body of T11. Working diagnoses included metastatic disease and
      lymphoma, and a biopsy of T7 and then T11 was carried out. Both showed
      pathological findings very suggestive of Paget's disease. Since CT is usually the
      more specific radiological examination in vertebral Paget's disease, we thought
      it could be useful to report this atypical CT presentation (patchy sclerosis of
      the vertebral body without diffuse bone texture changes and isolated involvement
      of the vertebral body) of vertebral Paget's disease. 

PMID- 24445957
TI  - Dual-energy CT in vertebral compression fractures: performance of visual and
      quantitative analysis for bone marrow edema demonstration with comparison to MRI.
AB  - OBJECTIVE: To prospectively evaluate the performance of virtual non-calcium (VNC)
      dual-energy CT (DECT) images for the demonstration of trauma-related abnormal
      marrow attenuation in collapsed and non-collapsed vertebral compression fractures
      (VCF) with MRI as a reference standard. MATERIALS AND METHODS: Twenty patients
      presenting with non-tumoral VCF were consecutively and prospectively included in
      this IRB-approved study, and underwent MRI and DECT of the spine. MR examination
      served as a reference standard. Two independent readers visually evaluated all
      vertebrae for abnormal marrow attenuation ("CT edema") on VNC DECT images;
      specificity, sensitivity, predictive values, intra and inter-observer agreements
      were calculated. A last reader performed a quantitative evaluation of CT numbers;
      cut-off values were calculated using ROC analysis. RESULTS: In the visual
      analysis, VNC DECT images had an overall sensitivity of 84%, specificity of 97%,
      and accuracy of 95%, intra- and inter-observer agreements ranged from k = 0.74 to
      k = 0.90. CT numbers were significantly different between vertebrae with edema on
      MR and those without (p < 0.0001). Cut-off values provided sensitivity of 85%
      (77%) and specificity of 82% (74%) for "CT edema" on thoracic (lumbar) vertebrae.
      CONCLUSIONS: VNC DECT images allowed an accurate demonstration of trauma-related
      abnormal attenuation in VCF, revealing the acute nature of the fracture, on both
      visual and quantitative evaluation.

PMID- 24445958
TI  - Copper-mediated C3-cyanation of indoles by the combination of amine and ammonium.
AB  - A copper-promoted C3-cyanation of both the free N-H and N-protected indoles by
      N,N,N',N'-tetramethyl-ethane-1,2-diamine (TMEDA) and ammonium is achieved. The
      iminium ion acts as the intermediate in this transformation, which is
      sequentially electrophilically attacked by indole and H2O followed by
      hydrolyzation to form the aldehyde. Then the reaction between the aldehyde and
      ammonium afforded nitriles. The reaction employs O2 as a clean oxidant with good
      efficiency and functional group tolerance. Thus, it represents a facile and safe
      procedure leading to 3-cyano indoles. 

PMID- 24445959
TI  - NLRC5 mediates cytokine secretion in RAW264.7 macrophages and modulated by the
      JAK2/STAT3 pathway.
AB  - The nucleotide-binding domain leucine-rich repeat proteins (NLRs), a class of
      innate immune receptors that respond to pathogen attack or cellular stress, have
      gained increasing attention. NLRC5 is the largest member of NLR family, which has
      recently been identified as a critical regulator of immune responses. In this
      study, we explore the role of NLRC5 in cytokine secretion and the role of the
      JAK2/STAT3 signaling pathway in lipopolysaccharide-induced NLRC5 expression in
      RAW264.7 cells. We demonstrated that overexpression of NLRC5 results in a
      downregulation of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) secretion; on the other hand, knockdown of NLRC5 by transfecting siRNA
      enhanced IL-6 and TNF-alpha secretion in RAW264.7 cells. These results indicated
      that NLRC5 plays a negative role in the regulation of IL-6 and TNF-alpha.
      Meanwhile, AG490 (a specific inhibitor of the JAK2/STAT3 signaling pathway) and
      JAK2 siRNA were used to manipulate JAK2/STAT3 activity. Finally, the results
      showed that AG490 and JAK2 siRNA inhibited NLRC5 expression and the expression
      levels of p-JAK2 and p-STAT3. We, for the first time, demonstrate that the
      inhibition of the JAK2/STAT3 signaling pathway results in decrease of NLRC5
      expression. 

PMID- 24445960
TI  - Inhibition of PI3Kdelta improves systemic lupus in mice.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease accompanying
      excessive inflammatory responses. Phosphoinositide 3-kinase p110delta (PI3Kdelta)
      is reported to associate with autoimmune conditions. We here aimed to determine
      whether selective inhibition of PI3Kdelta is effective in a lupus model of BXSB
      mice, using the selective PI3Kdelta inhibitor IC87114, which was
      intraperitoneally administrated to BXSB mice aged from 14 to 22 weeks. We showed
      that IC87114 improved renal function by decreasing the levels of proteinuria and
      serum creatinine, ameliorating the pathologic changes of kidneys and IgG and C3
      deposition. Serum anti-autoantibody to nuclear antigen, anti-dsDNA, IL-1beta, and
      IL-17 were markedly reduced by IC87114 therapy. Hepatic damage was also inhibited
      by administration of IC87114. Expression of phosphorylated AKT (p-AKT) and
      monocyte chemoattractant protein-1 was inhibited and mouse survival improved. In
      sum, PI3Kdelta activation may be a critical factor for escalating autoimmune
      renal and hepatic damage, and its inhibition may alleviate the autoimmune damage.
      Our study reveals that the selective blockade of PI3Kdelta is effective for mouse
      SLE. 

PMID- 24445961
TI  - Current developments in the use of biomarkers for juvenile idiopathic arthritis.
AB  - Use of biomarkers in clinical practice has proved extremely valuable and is a
      rapidly expanding field. However, despite the huge potential of biomarkers, for
      juvenile idiopathic arthritis (JIA) there are currently no validated paediatric
      biomarkers available to help with setting up a more tailored approach on which
      drug choice could be based, to achieve remission early in the course of disease.
      Early remission reduces burden of disease, limits side effects from toxic and
      unnecessary medication, and, most importantly, enhances quality of life. Several
      studies have suggested promising biomarkers: these may be a protein, cellular
      component, mRNA, or genetic component, for example a single nucleotide
      polymorphism (SNP). Here we describe recent developments in the use of biomarkers
      for JIA and their potential to assist in management of disease by predicting
      disease phenotype, severity, progression, and response to treatment, and
      determining when patients have reached stable remission and can safely
      discontinue treatment. 

PMID- 24445962
TI  - Is co-contraction responsible for the decline in maximal knee joint torque in
      older males?
AB  - While it is often reported that muscular coactivation increases with age, the
      mechanical impact of antagonist muscles, i.e., the antagonist torque, remains to
      be assessed. The aim of this study was to determine if the mechanical impact of
      the antagonist muscles may contribute to the age-related decline in the resultant
      torque during maximal voluntary contraction in knee flexion (KF) and knee
      extension (KE). Eight young (19-28 years old) and eight older (62-81 years old)
      healthy males participated in neuromuscular testing. Maximal resultant torque was
      simultaneously recorded with the electromyographic activity of quadriceps and
      hamstring muscles. The torque recorded in the antagonist muscles was estimated
      using a biofeedback technique. Resultant torques significantly decreased with age
      in both KF (-41 %, p < 0.005) and KE (-35 %, p < 0.01). Agonist and antagonist
      torques were significantly reduced in KF (-44 %, p < 0.05; -57 %, p < 0.05) and
      in KE (-37 %, p < 0.01; -50 %, p < 0.05). The torque elicited by double twitch
      stimulation (-37 %, p < 0.01) and the activation level (-12 %, p < 0.05) of
      quadriceps was significantly lower in older men compared to young men. This study
      showed that antagonist torques were not responsible for age-related declines in
      KF and KE resultant torques. Therefore, decreased resultant torques with age, in
      particular in KE, can primarily be explained by impairments of the peripheral
      factors (excitation-contraction coupling) as well as by decreased neural agonist
      activation. 

PMID- 24445963
TI  - Methodology developed for the simultaneous measurement of bone formation and bone
      resorption in rats based on the pharmacokinetics of fluoride.
AB  - This paper describes a novel methodology for the simultaneous estimation of bone
      formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive
      bone-seeker ion. The pharmacokinetics of flouride have been extensively studied
      in rats; its constants have all been characterized. This knowledge was the
      cornerstone for the underlying mathematical model that we used to measure bone
      fluoride uptake and elimination rate after a dose of fluoride. Bone resorption
      and formation were estimated by bone fluoride uptake and elimination rate,
      respectively. ROC analysis showed that sensitivity, specificity and area under
      the ROC curve were not different from deoxypiridinoline and bone alkaline
      phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone
      remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment)
      were used to validate the values obtained with this methodology. The results of
      BF and BR obtained with this technique were as expected for each biological
      model. Although the method should be performed under general anesthesia, it has
      several advantages: simultaneous measurement of BR and BF, low cost, and the use
      of compounds with no expiration date. 

PMID- 24445964
TI  - Evaluation of serum mesothelin in malignant and benign ovarian masses.
AB  - PURPOSE: To evaluate the diagnostic accuracy of serum mesothelin levels in
      patients with ovarian masses in comparison to serum cancer antigen (CA) 125
      levels. METHODS: This diagnostic accuracy study was conducted in a gynecological
      oncology unit at Ain Shams University Maternity hospital. Based on radiological
      and clinical findings, a total of 110 patients were consecutively recruited.
      Preoperative serum mesothelin levels were assessed using enzyme-linked
      immunosorbent assay (ELISA) technique, while CA125 levels were determined using
      electrochemiluminescence immunoassay. All patients underwent exploratory
      laparotomy. Preoperative serum levels of both markers were correlated to
      histopathological reports obtained from each patient. RESULTS: A total of 96
      patients were finally analyzed. Of the included 96 patients, 58 (60.4 %) had a
      benign ovarian lesion, while 38 (39.6 %) had a malignant lesion. The median serum
      CA125 levels were significantly higher in patients with malignant ovarian lesions
      than in patients with benign ovarian lesions [335.5 mIU/mL (range 60-1,127
      mIU/mL) versus 33.65 mIU/mL (range 10.36-174 mIU/mL), P < 0.001]. The median
      serum mesothelin level was significantly higher in patients with malignant
      ovarian lesions than in patients with benign ovarian lesions [104.1 nmol/L (range
      6.5-215.4 nmol/L) versus 12.65 nmol/L (range 6.5-102 nmol/L), P < 0.001]. The
      diagnostic sensitivity and specificity for mesothelin and CA125 were 97.4 and
      98.3 % and 97.4 and 56.9 %, respectively. The combination of mesothelin with
      CA125 did not add predictive value to mesothelin compared with mesothelin alone
      [same sensitivity (97.4 %) and same specificity (98.3 %)]. Serum mesothelin
      levels rather than serum CA125 levels were a significant predictor of early-stage
      ovarian malignancy [Area under the curve = 0.732, 95 % confidence interval (0.543
      0.921), P = 0.031]. CONCLUSION: In ovarian cancer, mesothelin seemed to have the
      same sensitivity, but a higher specificity than CA125. Combination of mesothelin
      and CA125 had no advantage over mesothelin alone. Mesothelin rather than CA125
      was a significant predictor of early-stage ovarian cancer (stage I/II).

PMID- 24445966
TI  - Triarylborane conjugated acacH ligands and their BF2 complexes: facile synthesis
      and intriguing optical properties.
AB  - A facile synthetic route for a new class of organoborane compounds (Mes)2B-arene
      acacH and (Mes)2B-arene-acacBF2 (Mes = mesityl and arene = C6H4 or C6Me4) is
      reported. The new dyads exhibit intriguing photophysical properties. A small
      structural change in spacer connecting the two chromophores leads to fine tuning
      of photophysical properties. The dyad containing 2,3,5,6-tetramethyl phenyl
      spacer acts as a selective "turn-on" chemodosimetric sensor for cyanide ion.
      Steric crowding around the boron centre significantly alters anion binding
      events. From NMR titration studies it is established that fluoride and cyanide
      follow different binding mechanisms which lead to intriguing optical properties
      in the reported probes. 

PMID- 24445967
TI  - Dramatic reduction of clindamycin plasma concentration in hidradenitis
      suppurativa patients treated with the rifampin-clindamycin combination.

PMID- 24445968
TI  - Blurred vision and epistaxis.

PMID- 24445969
TI  - The role of advanced lipid testing in the prediction of cardiovascular disease.
AB  - Advanced lipid testing has been suggested by some experts to identify patients
      with substantial residual risk for more aggressive targeting of lifestyle and
      pharmacologic therapies. It measures the subpopulation of lipoproteins and
      apolipoproteins, which include lipoprotein (a), apolipoprotein A-I, and
      apolipoprotein B, and measures of lipoprotein particle composition such as LDL
      particle (LPL-P) and HDL particle (HDL-P) number and size. Obesity is associated
      with smaller LDL-P and HDL-P sizes. Moderate weight loss via fasting/calorie
      restriction is associated with LDL-P size increase, whereas moderate weight loss
      via endurance exercise is associated with HDL-P size increase. Diets high in
      carbohydrates are associated with a more atherogenic advanced lipoprotein profile
      characterized by smaller LDL-P and HDL-P sizes. In summary, lifestyle changes
      such as weight loss, exercise, and dietary modification correlate with
      improvement in the profile of advanced lipoproteins. Regrettably, therapies
      targeting HDL and HDL composition have been disappointing to date. 

PMID- 24445970
TI  - Neural and muscular mechanisms of electrically induced fatigue in patients with
      spinal cord injury.
AB  - STUDY DESIGN: Intervention study. OBJECTIVES: The present study aimed at
      examining whether spinal and/or peripheral alterations are in the origin of
      neuromuscular fatigue development induced by intermittent neuromuscular
      electrical stimulation (NMES) in subjects with complete spinal cord injury (SCI).
      SETTING: Neurological Rehabilitation Center CMN Propara, Montpellier, France.
      METHODS: Thirteen volunteers with complete SCI participated in the study. The
      right triceps surae muscle was fatigued using a 30-Hz NMES protocol (2 s ON-2 s
      OFF) composed of three series of five trains. Spinal excitability (assessed by
      the H-reflex), muscle excitability (assessed by the M-wave), muscle contractile
      properties (assessed by mechanical response parameters) and torque evoked by NMES
      were tested before and after each five-train series. RESULTS: NMES-evoked torque
      significantly decreased throughout the protocol (P<0.001). This decrease was
      accompanied by a significant increase in M-wave amplitude (P<0.001), whereas H
      reflex and the Hmax/Mmax ratio were not significantly modified. The amplitude of
      the mechanical response was significantly decreased at the end of the protocol
      (P<0.05). CONCLUSION: The results indicate significant fatigue development, which
      was attributed to impaired cross-bridge force-generating capacity, without
      modification of spinal excitability nor muscle excitability.

PMID- 24445971
TI  - Epidemiology of traumatic spinal cord injuries in The Netherlands in 2010.
AB  - STUDY DESIGN: Retrospective files study. OBJECTIVE: To update epidemiological
      data on the incidence of traumatic spinal cord injury (TSCI) in The Netherlands.
      SETTING: The Netherlands. METHODS: From the Dutch National acute-care hospital
      database, all records of patients discharged with International Classification of
      Diseases 9th edition codes 806 or 952 in 2010 were selected. For each record, we
      requested an anonymised copy of the hospital discharge letter. We analysed the
      received letters for TSCI, defined as a newly acquired traumatic transverse
      lesion of the spinal cord or cauda equina, resulting in loss of motor, sensory,
      bladder or bowel function below the level of the lesion, lasting longer than 2
      weeks. We further extracted data on demographic and SCI characteristics and
      discharge destination. RESULTS: We received 372 discharge letters or a
      confirmation that the patient did not have TSCI. A total of 185 patients with
      TSCI were identified, of whom 30 died during acute-care hospital stay. We
      estimated the incidence of TSCI as 14.0 per million per annum including patients
      and 11.7 per million per annum excluding patients who did not survive the acute
      phase. Most patients were male (74%), had tetraplegia (69%) and an motor
      incomplete lesion (62%). Median age was 62 years (range 13-96). Discharge
      destination was a rehabilitation centre specialized in SCI in 78% of patients
      with motor complete TSCI and 47% of patients with motor incomplete TSCI.
      CONCLUSION: The estimated incidence of TSCI surviving the acute phase was 11.7
      per million per annum in the Netherlands in 2010. A substantial proportion of
      these patients was not referred to a specialized rehabilitation centre.

PMID- 24445972
TI  - Concurrent validity of the 10-meter walk test as compared with the 6-minute walk
      test in patients with spinal cord injury at various levels of ability.
AB  - STUDY DESIGN: Cross-sectional design. OBJECTIVES: To evaluate the concurrent
      validity of the 10-meter walk test (10MWT) as compared with the 6-minute walk
      test (6MinWT) in patients with spinal cord injury (SCI) at various levels of
      walking ability, as determined using the criteria from the functional
      independence measure locomotor (FIM-L) scores. SETTING: A major tertiary referral
      hospital in Thailand. METHODS: Ninety-four independent ambulatory subjects with
      SCI (FIM-L scores 5-7) were assessed for their functional abilities using the
      10MWT and 6MinWT. RESULTS: The data of the 10MWT and the 6MinWT had excellent
      correlation in subjects with FIM-L 7 (r=0.83, P<0.001), good correlation in
      subjects with FIM-L 6 (r=0.74, P<0.001), but poor correlation in subjects with
      FIM-L 5 (r=0.31, P>0.05). CONCLUSION: The 6MinWT is a thorough assessment to
      reflect functional endurance, but it requires a long time and a large area to
      administer. The findings confirm the utility of the 10MWT as an alternative
      monitoring tool to the 6MinWT, but only for the patients with rather good walking
      ability.

PMID- 24445973
TI  - Delayed spinal epidural hematoma following spinal anesthesia, far from needle
      puncture site.
AB  - STUDY DESIGN: Case report. OBJECTIVES: We report a case of spinal epidural
      hematoma (SEH) that appeared on the third postoperative day after lumbar spinal
      anesthesia, far from the needle puncture site. Possible mechanisms and
      etiological relation to patient's risk factors as well as diagnosis and
      management of SEH are briefly discussed. SETTING: Asklepieion General Hospital of
      Voula, Athens, Greece. METHODS AND RESULTS: A 64-year-old woman underwent an
      uneventful total knee arthroplasty operation under a spinal anesthetic. A lumbar
      puncture was performed in the L2-L3 interspace, that was atraumatic and
      successful on the first attempt. The operation was uneventful. On the third
      postoperative day, the patient developed a SEH that expanded from C2 to T3
      levels. She was presented with bilateral shoulder pain, muscle weakness of the
      upper extremities with normal sensation, followed by paraparesis. The magnetic
      resonance imaging (MRI) revealed a large vascular malformation, partially
      ruptured forming a hematoma compressing the spinal cord toward the vertebral
      bodies The patient was treated conservatively and full recovery was achieved.
      CONCLUSION: The possibility of SEH must be considered whenever neurological
      symptoms occur in the postoperative period, especially after a neuraxial
      blockade. The causes are multiple, a not-known lesion predisposing to bleeding
      and hematoma formation may preexist and the anesthetic technique can be directly
      or indirectly connected to this complication. MRI is the preferred diagnostic
      method.

PMID- 24445974
TI  - Breastfeeding by women with tetraplegia: some evidence for optimism.

PMID- 24445975
TI  - Response to 'Breastfeeding by women with tetraplegia: some evidence for
      optimism'.

PMID- 24445976
TI  - Oral erlotinib, but not rapamycin, causes modest acceleration of bladder and
      hindlimb recovery from spinal cord injury in rats.
AB  - OBJECTIVES: Erlotinib and Rapamycin are both in clinical use and experimental
      inhibition of their respective molecular targets, EGFR and mTORC1, has improved
      recovery from spinal cord injury. Our aim was to determine if daily Erlotinib or
      Rapamycin treatment started directly after spinal contusion injury in rats
      improves locomotion function or recovery of bladder function. SETTING: Stockholm,
      Sweden. METHODS: Rats were subjected to contusion injuries and treated during the
      acute phase with either Erlotinib or Rapamycin. Recovery of bladder function was
      monitored by measuring residual urine volume and hindlimb locomotion assessed by
      open-field observations using the BBB rating scale as well as by automated
      registration of gait parameters. Body weights were monitored. To determine
      whether Erlotinib and Rapamycin inhibit the same signaling pathway, a cell
      culture system and western blots were used. RESULTS: Erlotinib accelerated
      locomotor recovery and slightly improved bladder recovery; however, we found no
      long-term improvements of locomotor function. Rapamycin did neither improved
      locomotor function nor bladder recovery. In vitro studies confirmed that
      Erlotinib and Rapamycin both inhibit the EGFR-mTORC1 signaling pathway.
      CONCLUSION: We conclude that none of these two drug regimes improved long-term
      functional outcome in our current model of spinal cord injury. Nevertheless, oral
      treatment with Erlotinib may offer modest temporary advantages, whereas treatment
      with Rapamycin does not.

PMID- 24445978
TI  - Applanation tonometry: a reliable technique to assess aortic pulse wave velocity
      in spinal cord injury.
AB  - STUDY DESIGN: Within-subject repeated measures. OBJECTIVES: To determine the
      intra- and inter-tester reliability of aortic pulse wave velocity (aPWV)
      measurements collected using applanation tonometry in individuals with spinal
      cord injury (SCI). SETTING: Inpatient Rehabilitation Centre and outpatient Clinic
      in Vancouver, BC, Canada. METHODS: Fifteen men and three women with traumatic SCI
      (age: 46+/-16 years; C3-L1; American Spinal Injury Association Impairment Scale A
      D; 2-284 months post injury) participated in two testing sessions separated by an
      average of 2 days. During each testing session, aPWV measurements were collected
      in the supine position following 10 min of rest. Arterial blood pressure
      waveforms were collected simultaneously by two trained raters at the carotid and
      femoral arterial sites using applanation tonometry. Heart rate was continuously
      measured using a single-lead electrocardiogram, whereas brachial blood pressures
      were measured at 5-min intervals using an automated device. RESULTS: Intra- and
      inter-tester aPWV measurements demonstrated almost perfect reliability with
      intraclass correlation coefficients of 0.91 and 0.98 (P<0.001), and coefficients
      of variation of 5.9% and 3.4%, respectively. The smallest detectable differences
      (SDDs) for intra- and inter-tester measurements were 0.9 m s(-1) and 0.6 m s(-1),
      respectively. There were no significant differences in heart rate or blood
      pressure between intra- and inter-testing sessions. CONCLUSION: Applanation
      tonometry measurements of aPWV are reliable in individuals with SCI. In addition,
      the SDDs were smaller than a clinically relevant value, suggesting that this
      measurement is suitable for repeated measures study designs in SCI.

PMID- 24445977
TI  - Urologic health condition of spinal cord-injured patients living in Turkey.
AB  - OBJECTIVES: To determine the urologic health condition of spinal cord-injured
      (SCI) patients living in Turkey, and to analyze the relationship between the
      prevalence of urologic health condition parameters and the patient's
      characteristics. METHODS: Telephone call survey was conducted with a structured
      questionnaire among all members of Turkish Society of Spinal Cord Injured
      Patients. RESULTS: Data were obtained from 300 patients. Mean age was 42 years
      with a male/female ratio of 2.3, while the most common cause of injury was
      transport (35.3%). Although 70% were aware of potential kidney and bladder
      problems after injury >60% of the patients were not under regular urologic follow
      up. Secondary health problems experienced as being most important was urination
      problems (50%). Of the patients 72.7% (83% in females vs 68% in males) had
      urinary incontinence (UI) during last 3 months, and 64.3% used clean intermittent
      catheterization (CIC) (68% in males vs. 56% in females), while 73%, 57% and 26%
      of incontinent patients used diaper/pad, medication and condom catheter,
      respectively, and the use of CIC decreased with time. Surgical procedures on
      urinary tract were performed in 22.6% of the patients; stone surgeries were the
      most frequent ones. CONCLUSION: This study demonstrated that the UI rate was high
      among SCI patients, and more common in females with fairly good proportion of
      patients using incontinence medication. Main bladder management method was CIC
      and more prevalent in males, although the use of CIC decreased with time. Urinary
      stone surgery was the leading surgical procedure.

PMID- 24445979
TI  - Thirteen Patients with MAT1A Mutations Detected Through Newborn Screening: 13
      Years' Experience.
AB  - BACKGROUND: Methionine adenosyltransferase I/III (MATI/III) deficiency is the
      most common genetic cause of persistent isolated hypermethioninemia. Patients and
      Methods : This is a retrospective data analysis of 62 newborns with elevated
      methionine detected by newborn screening between January 2000 and June 2013. The
      clinical, biochemical, and molecular findings of a subset of these children with
      MAT1A mutations associated with MATI/III deficiency are presented. RESULTS: Of
      the 62 newborns with elevated methionine, 12 were identified as having classical
      homocystinuria; 37 were false-positives; and 13 were found to have isolated
      persistent hypermethioninemia in the absence of biochemical markers of
      homocystinuria, abnormal liver function studies, or other causes of elevated
      methionine. These 13 individuals underwent genetic testing for changes in the
      MAT1A gene, associated with MATI/III deficiency. Three of 13 were found to have
      the common autosomal dominant R264H mutation, one was found to be a compound
      heterozygote for two novel pathogenic mutations, and three were found to be
      heterozygotes for previously reported mutations shown to cause autosomal
      recessive MATI/III deficiency when present in homozygous or a compound
      heterozygous configuration. The remaining six patients had variants of unknown
      clinical significance or novel mutations. For the majority of individuals,
      methionine persisted above the normal range but trended downward over time. None
      of these 13 individuals was started on a low-methionine diet, and all have age
      appropriate growth and development. CONCLUSION: These cases show that individuals
      with even single changes in the MAT1A gene may have elevations in methionine
      identified by newborn screening, which may persist for months after birth without
      any clinical consequences.

PMID- 24445980
TI  - Comparison of high-frequency oscillatory ventilation and conventional mechanical
      ventilation in pediatric respiratory failure.
AB  - IMPORTANCE: Outcomes associated with use of high-frequency oscillatory
      ventilation (HFOV) in children with acute respiratory failure have not been
      established. OBJECTIVE: To compare the outcomes of HFOV with those of
      conventional mechanical ventilation (CMV) in children with acute respiratory
      failure. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective,
      observational study using deidentified data obtained from all consecutive
      patients receiving mechanical ventilation aged 1 month to 18 years in the Virtual
      PICU System database from January 1, 2009, through December 31, 2011. The study
      population was divided into 2 groups: HFOV and CMV. The HFOV group was further
      divided into early and late HFOV. Propensity score matching was performed as a 1
      to-1 match of HFOV and CMV patients. A similar matching process was performed for
      early HFOV and CMV patients. EXPOSURE: High-frequency oscillatory ventilation.
      MAIN OUTCOMES AND MEASURES: Length of mechanical ventilation, intensive care unit
      (ICU) length of stay, ICU mortality, and standardized mortality ratio (SMR).
      RESULTS: A total of 9177 patients from 98 hospitals qualified for inclusion. Of
      these, 902 (9.8%) received HFOV, whereas 8275 (90.2%) received CMV. A total of
      1764 patients were matched to compare HFOV and CMV, whereas 942 patients were
      matched to compare early HFOV and CMV. Length of mechanical ventilation (CMV vs
      HFOV: 14.6 vs 20.3 days, P < .001; CMV vs early HFOV: 14.6 vs 15.9 days, P <
      .001), ICU length of stay (19.1 vs 24.9 days, P < .001; 19.3 vs 19.5 days, P =
      .03), and mortality (8.4% vs 17.3%, P < .001; 8.3% vs 18.1%, P < .001) were
      significantly higher in HFOV and early HFOV patients compared with CMV patients.
      The SMR in the HFOV group was 2.00 (95% CI, 1.71-2.35) compared with an SMR in
      the CMV group of 0.85 (95% CI, 0.68-1.07). The SMR in the early HFOV group was
      1.62 (95% CI, 1.31-2.01) compared with an SMR in the CMV group of 0.76 (95% CI,
      0.62-1.16). CONCLUSIONS AND RELEVANCE: Application of HFOV and early HFOV
      compared with CMV in children with acute respiratory failure is associated with
      worse outcomes. The results of our study are similar to recently published
      studies in adults comparing these 2 modalities of ventilation for acute
      respiratory distress syndrome.

PMID- 24445981
TI  - Chloral hydrate, chloral hydrate--promethazine and chloral hydrate -hydroxyzine
      efficacy in electroencephalography sedation.
AB  - OBJECTIVE: To compare efficacy and safety of chloral hydrate (CH), chloral
      hydrate and promethazine (CH + P) and chloral hydrate and hydroxyzine (CH + H) in
      electroencephalography (EEG) sedation. METHODS: In a parallel single-blinded
      randomized clinical trial, ninety 1-7 y-old uncooperative kids who were referred
      to Pediatric Neurology Clinic of Shahid Sadoughi University, Yazd, Iran from
      April through August 2012, were randomly assigned to receive 40 mg/kg of chloral
      hydrate or 40 mg/kg of chloral hydrate and 1 mg/kg of promethazine or 40 mg/kg of
      chloral hydrate and 2 mg/kg of hydroxyzine. The primary endpoint was efficacy in
      sufficient sedation (obtaining four Ramsay sedation score) and successful
      completion of EEG. Secondary endpoint was clinical adverse events. RESULTS:
      Thirty nine girls (43.3 %) and 51 boys (56.7 %) with mean age of 3.34 +/- 1.47 y
      were assessed. Sufficient sedation and completion of EEG were achieved in 70 % (N
      = 21) of chloral hydrate group, in 83.3 % (N = 25) of CH + H group and in 96.7 %
      (N = 29) of CH + P group (p = 0.02). Mild clinical adverse events including
      vomiting [16.7 % (N = 5) in CH, 6.7 % (N = 2) in CH + P, 6.7 % (N = 2) in CH +
      H], agitation in 3.3 % of CH + P (N = 1) group and mild transient hypotension in
      3.3 % of CH + H (N = 1) group occurred. Safety of these three sedation regimens
      was not statistically significant different (p = 0.14). CONCLUSIONS: Combination
      of chloral hydrate-antihistamines can be used as the most effective and safe
      sedation regimen in drug induced sleep electroencephalography of kids.

PMID- 24445982
TI  - Serum 25 hydroxy vitamin D insufficiency associated with bronchial asthma in
      Lucknow, India.
AB  - OBJECTIVES: To assess the association between serum 25 hydroxy vitamin D levels
      and asthma and its control in Indian children. METHODS: This was a prospective
      case-control study conducted in tertiary care hospital. Cases of asthma and
      healthy age-matched controls were included, aged 1-15 y, who had not received any
      vitamin D supplementation in the last year and had no other co-morbidity, after
      obtaining written informed parental consent. 25 hydroxy vitamin D insufficiency
      was taken below level of <= 30 ng/mL. RESULTS: Fifty asthmatics and 25 age
      matched controls were recruited from August 2011-July 2012. 25 hydroxy vitamin D
      insufficiency was associated with occurrence of asthma (OR = 13.5; 95 % CI = 4.25
      42.85: p = 0.000). With decreasing level of asthma control there was increasing
      strength of association with 25 hydroxy vitamin D insufficiency [chi (2) for
      trend = 24.96 (p = 0.000)]. CONCLUSIONS: 25 hydroxy vitamin D insufficiency is
      associated with bronchial asthma as well as its level of control.

PMID- 24445983
TI  - Meromelia in a newborn- a rare congenital anomaly.

PMID- 24445984
TI  - Bed wetting--silent suffering: an approach to enuresis and voiding disorders in
      children: authors' reply.

PMID- 24445985
TI  - Bed wetting--silent suffering: an approach to enuresis and voiding disorders in
      children: correspondence.

PMID- 24445986
TI  - Catalytic metal-free Si-N cross-dehydrocoupling.
AB  - The metal-free B(C6F5)3 catalyzed dehydrocoupling of hydrosilanes with anilines,
      carbazoles and indoles is reported. For anilines and carbazoles the reaction
      proceeds by the liberation of H2 as the sole Si-N coupling byproduct. Indoles
      react with diphenyl(methyl) hydrosilane to give N-silyl indolines with high
      diastereoselectivity (d.r. 10 : 1) in excellent yields. A mechanism for this Si-N
      coupling/hydrogenation sequence is proposed. 

PMID- 24445988
TI  - Biocompatibility of nano-hydroxyapatite/Mg-Zn-Ca alloy composite scaffolds to
      human umbilical cord mesenchymal stem cells from Wharton's jelly in vitro.
AB  - Seeding cells and scaffolds play pivotal roles in bone tissue engineering and
      regenerative medicine. Wharton's jelly-derived mesenchymal stem cells (WJCs) from
      human umbilical cord represent attractive and promising seeding cells in tissue
      regeneration and engineering for treatment applications. This study was carried
      out to explore the biocompatibility of scaffolds to seeding cells in vitro. Rod
      like nano-hydroxyapatite (RN-HA) and flake-like micro-hydroxyapatite (FM-HA)
      coatings were prepared on Mg-Zn-Ca alloy substrates using micro-arc oxidation and
      electrochemical deposition. WJCs were utilized to investigate the cellular
      biocompatibility of Mg-Zn-Ca alloys after different surface modifications by
      observing the cell adhesion, morphology, proliferation, and osteoblastic
      differentiation. The in vitro results indicated that the RN-HA coating group was
      more suitable for cell proliferation and cell osteoblastic differentiation than
      the FM-HA group, demonstrating better biocompatibility. Our results suggested
      that the RN-HA coating on Mg-Zn-Ca alloy substrates might be of great potential
      in bone tissue engineering. 

PMID- 24445987
TI  - The metabolic signature of C9ORF72-related ALS: FDG PET comparison with
      nonmutated patients.
AB  - PURPOSE: Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene,
      located on chromosome 9p21 has been demonstrated to be the commonest cause of
      familial amyotrophic lateral sclerosis (ALS) and to account for 5 to 10 % of
      apparently sporadic ALS. Relatively little is known about the brain metabolism
      profile of patients carrying the expansion. Our aim was to identify the
      [(18)F]FDG PET profile in ALS patients with the C9ORF72 expansion (C9ORF72-ALS).
      METHODS: Fifteen C9ORF72-ALS patients were compared with 12 patients with ALS and
      comorbid frontotemporal dementia (FTD) without the C9ORF72 expansion (ALS-FTD)
      and 30 cognitively normal patients with ALS without mutations of ALS-related
      genes (sALS). The three groups were then cross-matched to 40 neurologically
      normal controls. All patients underwent FDG PET within 4 months of diagnosis.
      RESULTS: The C9ORF72-ALS patients compared with the sALS patients showed
      significant hypometabolism in the anterior and posterior cingulate cortex,
      insula, caudate and thalamus, the left frontal and superior temporal cortex, and
      hypermetabolism in the midbrain, bilateral occipital cortex, globus pallidus and
      left inferior temporal cortex. The ALS-FTD patients compared with the sALS
      patients showed more limited hypometabolic areas, including the orbitofrontal,
      prefrontal, anterior cingulate and insular cortex, and hypermetabolic areas,
      including the bilateral occipital cortex, the left precentral and postcentral
      cortex and superior temporal gyrus. The C9ORF72-ALS patients compared with the
      ALS-FTD patients showed hypometabolism in the left temporal cortex. CONCLUSION:
      ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more
      widespread central nervous system involvement than ALS patients without genetic
      mutations, with or without comorbid FTD, consistent with their more severe
      clinical picture.

PMID- 24445989
TI  - Collagen scaffolds modified with collagen-binding bFGF promotes the neural
      regeneration in a rat hemisected spinal cord injury model.
AB  - Nerve conduit is one of strategies for spine cord injury (SCI) treatment.
      Recently, studies showed that biomaterials could guide the neurite growth and
      promote axon regeneration at the injury site. However, the scaffold by itself was
      difficult to meet the need of SCI functional recovery. The basic fibroblast
      growth factor (bFGF) administration significantly promotes functional recovery
      after organ injuries. Here, using a rat model of T9 hemisected SCI, we aimed at
      assessing the repair capacity of implantation of collagen scaffold (CS) modified
      by collagen binding bFGF (CBD-bFGF). The results showed that CS combined with CBD
      bFGF treatment improved survival rates after the lateral hemisection SCI. The
      CS/CBD-bFGF group showed more significant improvements in motor than the simply
      CS-implanted and untreated control group, when evaluated by the 21-point Basso
      Beattie-Bresnahan (BBB) score and footprint analysis. Both hematoxylin and eosin
      (H&E) and immunohistochemical staining of neurofilament (NF) and glial fibrillary
      acidic protein (GFAP) demonstrated that fibers were guided to grow through the
      implants. These findings indicated that administration of CS modified with CBD
      bFGF could promote spinal cord regeneration and functional recovery. 

PMID- 24445990
TI  - Copy number variants and therapeutic response to antidepressant medication in
      major depressive disorder.
AB  - It would be beneficial to find genetic predictors of antidepressant response to
      help personalise treatment of major depressive disorder (MDD). Rare copy number
      variants (CNVs) have been implicated in several psychiatric disorders, including
      MDD, but their role in antidepressant response has yet to be investigated. CNV
      data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods
      leading to New Medications in Depression and Schizophrenia) consortium with
      prospective data on treatment outcome with either a serotonergic or noradrenergic
      antidepressant. No association was seen between the presence of CNV (rare or
      common), the overall number of CNVs or genomic CNV 'burden' and antidepressant
      response. Specific CNVs were nominally associated with antidepressant response,
      including 15q13.3 duplications and exonic NRXN1 deletions. These were associated
      with poor response to antidepressants. Overall burden of CNVs is unlikely to
      contribute to personalising antidepressant treatment. Specific CNVs associated
      with antidepressant treatment require replication and further study to confirm
      their role in the therapeutic action of antidepressant. 

PMID- 24445991
TI  - A rare loss-of-function SCN5A variant is associated with lidocaine-induced
      ventricular fibrillation.
AB  - The human genome contains over 4 million variant sites, as compared with the
      reference genome, including rare sequence variants, which have the potential to
      exert large phenotypic effects, such as susceptibility to drug toxicity. We
      report identification and functional characterization of a rare non-synonymous
      (p.A1427S) variant in the SCN5A gene that was associated with incessant and
      lethal ventricular tachycardia and fibrillation after administration of lidocaine
      to a patient with acute myocardial infarction. The variant, located in a highly
      conserved domain distinct from the predicted lidocaine-binding site, decreased
      peak current density of the sodium channel. With the increasing availability of
      the whole exome and whole genome sequencing data, it would be possible to
      identify and characterize rare variants in SCN5A that might predispose to lethal
      ventricular arrhythmias. 

PMID- 24445992
TI  - High-temperature antiferromagnetism in molecular semiconductor thin films and
      nanostructures.
AB  - The viability of dilute magnetic semiconductors in applications is linked to the
      strength of the magnetic couplings, and room temperature operation is still
      elusive in standard inorganic systems. Molecular semiconductors are emerging as
      an alternative due to their long spin-relaxation times and ease of processing,
      but, with the notable exception of vanadium-tetracyanoethylene, magnetic
      transition temperatures remain well below the boiling point of liquid nitrogen.
      Here we show that thin films and powders of the molecular semiconductor cobalt
      phthalocyanine exhibit strong antiferromagnetic coupling, with an exchange energy
      reaching 100 K. This interaction is up to two orders of magnitude larger than in
      related phthalocyanines and can be obtained on flexible plastic substrates, under
      conditions compatible with routine organic electronic device fabrication. Ab
      initio calculations show that coupling is achieved via superexchange between the
      singly occupied a1g () orbitals. By reaching the key milestone of magnetic
      coupling above 77 K, these results establish quantum spin chains as a potentially
      useable feature of molecular films. 

PMID- 24445993
TI  - [Recreational and competitive alpine skiing. Typical injury patterns and
      possibilities for prevention].
AB  - Alpine skiing is the most popular winter sport discipline in Germany and is
      performed by more than 4 million recreational sportsmen and ski racing athletes.
      Compared to other sports, however, the injury rate in alpine skiing is quite
      high. Especially the knee joint is the most commonly injured area of the
      musculoskeletal system. Knee injuries are classified as severe in a high
      percentage of cases. In this review article, epidemiologic data and typical
      injury patterns in recreational alpine skiing and in competitive alpine ski
      racing are compared. In addition, the potentials of preventive methods in alpine
      skiing are presented and evaluated with a special focus on orthotic devices and
      protection wear as injury prevention equipment. 

PMID- 24445994
TI  - [Flaps for soft tissue defect closure in the distal lower leg].
AB  - Soft tissue defects in the distal lower leg region are challenging to treat,
      especially in trauma cases. To achieve early closure of the defect, pediculated
      adipofascial or muscle flaps can be used as well as free flaps. The pediculated
      adipofascial suralis flap has a reliable blood supply and a broad radius so this
      flap can be used for almost every defect location on the distal lower leg except
      for defects larger than 10 * 10 cm. The donor site defect does not lead to major
      problems and is well tolerated. The soleus flap can cover defects in the middle
      third and proximal distal third of the lower leg with its muscle. The donor site
      defect is occasionally associated with reduced calf functioning but is tolerated
      well most of the time. Because of these advantages, the pediculated adipofacial
      suralis flap and the soleus muscle flap can be used instead a microvascular free
      flap for the closure of defects in the distal lower leg region. 

PMID- 24445995
TI  - [Trauma room time out (TRTO). New safety checklist to improve patient safety and
      employee satisfaction in the emergency room].

PMID- 24445996
TI  - Chitosan-modified cobalt oxide nanoparticles stimulate TNF-alpha-mediated
      apoptosis in human leukemic cells.
AB  - The objective of this study was to develop chitosan-based delivery of cobalt
      oxide nanoparticles to human leukemic cells and investigate their specific
      induction of apoptosis. The physicochemical properties of the chitosan-coated
      cobalt oxide nanoparticles were characterized using transmission electron
      microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform
      infrared spectroscopy. The solubility of chitosan-coated cobalt oxide
      nanoparticles was higher at acidic pH, which helps to release more cobalt ions
      into the medium. Chitosan-coated cobalt oxide nanoparticles showed good
      compatibility with normal cells. However, our results showed that exposure of
      leukemic cells (Jurkat cells) to chitosan-coated cobalt oxide nanoparticles
      caused an increase in reactive oxygen species generation that was abolished by
      pretreatment of cells with the reactive oxygen species scavenger N-acetyl-L
      cysteine. The apoptosis of Jurkat cells was confirmed by flow-cytometric
      analysis. Induction of TNF-alpha secretion was observed from stimulation of
      Jurkat cells with chitosan-coated cobalt oxide nanoparticles. We also tested the
      role of TNF-alpha in the induction of Jurkat cell death in the presence of TNF
      alpha and caspase inhibitors. Treatment of leukemic cells with a blocker had a
      greater effect on cancer cell viability. From our findings, oxidative stress and
      caspase activation are involved in cancer cell death induced by chitosan-coated
      cobalt oxide nanoparticles. 

PMID- 24445997
TI  - Roles of Atox1 and p53 in the trafficking of copper-64 to tumor cell nuclei:
      implications for cancer therapy.
AB  - Owing to its cytotoxicity, free copper is chelated by protein side chains and
      does not exist in vivo. Several chaperones transport copper to various cell
      compartments, but none have been identified that traffic copper to the nucleus.
      Copper-64 decays by beta (+) and beta (-) emission, allowing positron emission
      tomography and targeted radionuclide therapy for cancer. Because the delivery of
      (64)Cu to the cell nucleus may enhance the therapeutic effect of copper
      radiopharmaceuticals, elucidation of the pathway(s) involved in transporting
      copper to the tumor cell nucleus is important for optimizing treatment. We
      identified Atox1 as one of the proteins that binds copper in the nucleus. Mouse
      embryonic fibroblast cells, positive and negative for Atox1, were used to
      determine the role of Atox1 in (64)Cu transport to the nucleus. Mouse embryonic
      fibroblast Atox1(+/+) cells accumulated more (64)Cu in the nucleus than did
      Atox1(-/-) cells. HCT 116 colorectal cancer cells expressing p53 (+/+) and not
      expressing p53 (-/-) were used to evaluate the role of this tumor suppressor
      protein in (64)Cu transport. In cells treated with cisplatin, the uptake of
      (64)Cu in the nucleus of HCT 116 p53(+/+) cells was greater than that in HCT 116
      p53(-/-) cells. Atox1 expression increased in HCT 116 p53(+/+) and p53(-/-) cells
      treated with cisplatin; however, Atox1 localized to the nuclei of p53(+/+) cells
      more than in the p53(-/-) cells. The data presented here indicate that Atox1 is
      involved in copper transport to the nucleus, and cisplatin affects nuclear
      transport of (64)Cu in HCT 116 cells by upregulating the expression and the
      nuclear localization of Atox1. 

PMID- 24445998
TI  - Synthesis, characterization, and binding properties towards CT-DNA and
      lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its
      derivatives and triphenylphosphine.
AB  - Mixed-ligand silver(I) complexes of formulae [AgCl(TPP)2(MTZD)] (1),
      {[AgCl(TPP)2(MBZT)].(MBZT).2(toluene)} (2), and [AgCl(TPP)2(CMBZT)] (3) were
      obtained by refluxing toluene solutions of silver(I) chloride with
      triphenylphosphine (TPP) and the appropriate heterocyclic thioamides 2
      mercaptothiazolidine (MTZD), 2-mercaptobenzothiazole (MBZT), and 5-chloro-2
      mercaptobenzothiazole (CMBZT). The complexes were characterized by the melting
      point, vibrational spectroscopy (Fourier transform mid-IR), (1)H-NMR
      spectroscopy, UV-vis spectroscopy, and X-ray crystallography. DNA binding tests
      indicate the ability of complexes 1-3 to modify the activity of cells. The
      binding constants of 1-3 towards calf-thymus DNA (CT-DNA) [(3.5 +/- 8.5) * 10(4)
      M(-1) for 1, (10.0 +/- 0.0) * 10(4) M(-1) for 2, and (46.4 +/- 7.0) * 10(4) M(-1)
      for 3] indicate strong interaction of 3. Changes in the fluorescence of ethidium
      bromide in the presence of DNA suggest intercalation into or electrostatic
      interactions with DNA. The corresponding apparent binding constants (K app)
      towards CT-DNA calculated through fluorescence spectra are (3.5 +/- 0.7) * 10(4)
      M(-1) for 1, (10.0 +/- 0.0) * 10(4) M(-1) for 2, and (46.4 +/- 7.0) * 10(4) M(-1)
      for 3. Docking studies on DNA complexes confirm the binding of 1 and 2 in the
      major groove of CT-DNA and of 3 in the minor groove. Moreover, the influence of 1
      3 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by
      the enzyme lipoxygenase was studied kinetically and theoretically. The
      antibacterial effect of 1-3 against the bacterial species Pseudomonas aeruginosa
      and Escherichia coli was evaluated. Complex 1 exhibits the strongest activity. 

PMID- 24445999
TI  - A dual role for autophagy in a murine model of lung cancer.
AB  - Autophagy is a mechanism by which starving cells can control their energy
      requirements and metabolic states, thus facilitating the survival of cells in
      stressful environments, in particular in the pathogenesis of cancer. Here we
      report that tissue-specific inactivation of Atg5, essential for the formation of
      autophagosomes, markedly impairs the progression of KRas(G12D)-driven lung
      cancer, resulting in a significant survival advantage of tumour-bearing mice.
      Autophagy-defective lung cancers exhibit impaired mitochondrial energy
      homoeostasis, oxidative stress and a constitutively active DNA damage response.
      Genetic deletion of the tumour suppressor p53 reinstates cancer progression of
      autophagy-deficient tumours. Although there is improved survival, the onset of
      Atg5-mutant KRas(G12D)-driven lung tumours is markedly accelerated.
      Mechanistically, increased oncogenesis maps to regulatory T cells. These results
      demonstrate that, in KRas(G12D)-driven lung cancer, Atg5-regulated autophagy
      accelerates tumour progression; however, autophagy also represses early
      oncogenesis, suggesting a link between deregulated autophagy and regulatory T
      cell controlled anticancer immunity. 

PMID- 24446001
TI  - [New Year - Everything remains the same?].

PMID- 24446003
TI  - [Residual relaxant block due to pseudocholinesterase deficiency - First
      manifestation in an elderly patient].
AB  - Pseudocholinesterase or butyrylcholinesterase (BChE) inactivates the relaxant
      drugs mivacurium and suxamethonium. A deficiency in plasma activity of this
      enzyme may result in prolonged muscular paralysis and subsequently the need for
      an extended duration of mechanical ventilation. We report the case of a 65-year
      old patient who was diagnosed with butyrylcholinesterase deficiency for the first
      time during elective surgery. Neuromuscular monitoring constitutes a central
      diagnostic asset in ensuring patient safety. 

PMID- 24446004
TI  - [Anaesthesia for extrathoracal vascular surgery - Part 2: anaesthesiological
      management].
AB  - The anaesthesiological management in patients undergoing vascular surgical
      procedure need an individual approach, because of the high incidence of
      coexisting diseases with an increased risk of cardiovascular complications. The
      choice of anaesthesiogical method und perioperative monitoring depends on planned
      vascular procedures. 

PMID- 24446005
TI  - [Nausea and vomiting after anaesthesia for children - Big problems for little
      patients].
AB  - Postoperative nausea and vomiting are undesirable and unpleasant side effects
      after surgery and anaesthesia associated with delayed oral intake and
      postoperative recovery, and impaired parental satisfaction. Since current
      modalities against PONV are cheap, highly effective, and almost free from
      relevant side-effects - providing contraindications are appropriately considered 
      , recommendations tend to move away from risk-score guided administration of
      antiemetic towards a more liberal administration policy or even favour routine
      administration to children undergoing general anaesthesia for surgery combined
      with total-intrevanous anaesthesia using propfol and reduction of perioperative
      opioid administration. 

PMID- 24446006
TI  - [Hospital hygiene - Where are we in the sixth year of "Operation Clean Hands"?].
AB  - The national German hand hygiene campaign is implementing the WHO patient safety
      initiative "Clean Care is Safer Care". After 6 years over 1400 health care
      institutions are participating in the campaign on a voluntary basis. The
      implementation of the multimodal intervention concept including improvement of
      alcohol based hand rub availability, the introduction of 2 surveillance methods
      and of the WHO "My 5 Moments of Hand Hygiene Model" in those health care
      facilities, participating for several years, increased median hand hygiene
      compliance by 11% and alcohol based hand rub availability by 61%. 

PMID- 24446007
TI  - [Cardiac and thoracic vascular surgery - "More exciting than a thriller!"].

PMID- 24446008
TI  - [Indications, risk factors, specialities and after-care of surgical treatment for
      cardiac and thoracic vascular diseases].
AB  - Despite a known high risk and complexity in the operative therapy of cardio
      thoracic patients, cardiac surgery is medical routine activity today. The German
      Society of Cardiothoracic Surgery regularly analyses the more than 100.000 cases
      a year in Germany. Fixing procedural statics, it gives us the knowledge of
      individual risk factors and success rates for surgical therapy of our
      patients.Following we want to shortly summarize indications, risk factors,
      specialities and after-care of surgical treatment for cardiac and thoracic
      vascular diseases in adults. 

PMID- 24446009
TI  - [Coagulation disorders in the context of cardiac surgery - Clinical basics and
      mechanism based therapy].
AB  - Intra- and postoperative bleeding disorders are common in cardiac surgery. The
      etiology of perioperative coagulopathy frequently becomes apparent as a
      combination of several acquired and inherited disorders. Differential diagnosis
      of microvascular bleeding include altered homeostasis (e.g. anemia, hypothermia,
      acidosis, hypocalcemia), impaired primary hemostasis, antithrombotic medication,
      dilutive and consumptive coagulopathy, fibrinolysis and the absence or deficiency
      of coagulation factors. Timely detection of underlying pathology and subsequent
      rigorous treatment has the potential to minimize perioperative transfusion
      requirements, prevent resternotomy and improve patient outcome remarkably. Point
      of-care-systems can provide fast bed-sided analysis, which contribute to early
      diagnosis and intervention. Individual and regularly revised algorithms, adapted
      to the individualized institutional infrastructure, may facilitate resource
      saving treatment of perioperative coagulopathy.

PMID- 24446010
TI  - [Vascular cannulation and hemodynamic monitoring for cardiac and thoracic
      vascular surgery - a review].
AB  - Cardiac surgery requires cardiopulmonary bypass (CPB) with extracorporeal
      circulation (ECC) for intracardiac procedures. The surgical strategy determines
      access for monitoring and insertion sites with high-flow cannulas. The
      perioperative care of cardiac surgical patients requires adequate hemodynamic
      monitoring for reasonable catecholamine therapy and fluid management. Therefore,
      the knowledge of the vascular anatomy is essential to provide professional care
      to patients undergoing ECC during thoracic vascular and cardiac surgery. This
      article is a review of hemodynamic monitoring and access for ECC in patients for
      adult cardiac surgery for anaesthesiologists and intensivists. 

PMID- 24446013
TI  - A singly bonded amido-distannyne: H(2) activation and isocyanide coordination.
AB  - The first amido-distannyne, L(?)SnSnL(?) (L(?) = -N(Ar(?))(SiPr(i)3), Ar(?) =
      C6H2{C(H)Ph2}2Pr(i)-2,6,4), has been prepared and shown to possess a very long Sn
      Sn single bond; the compound activates dihydrogen under ambient conditions to
      give L(?)Sn(MU-H)2SnL(?), and reacts with Bu(t)NC to give a stable adduct
      complex, L(?)(Bu(t)NC)SnSn(CNBu(t))L(?). 

PMID- 24446014
TI  - Characterizing solid renal neoplasms with MRI in adults.
AB  - Until recently, most solid renal neoplasms without macroscopic fat were presumed
      to represent renal cell carcinoma and were indiscriminately treated with
      nephrectomy. Expanding surgical options and ablative technologies, a growing
      acceptance of renal mass biopsy, the advent of targeted molecular agents, and
      advances in our understanding of tumor biology have challenged the wisdom of this
      approach and are ushering in a potential new era in which therapy is linked to
      histologic subtype and cytogenetics. This approach mandates evolution of our
      diagnostic algorithm beyond the distinction between solid and cystic and
      enhancing and nonenhancing. Computed tomography (CT) has traditionally been the
      imaging technique of choice for evaluating potential solid renal tumors, in large
      part due to its widespread availability, high spatial resolution, calcium
      discrimination, and multiphase, enhanced imaging capabilities. For the most part,
      however, CT is limited to characterization based upon the attenuation and
      enhancement characteristics of a lesion and necessitates exposure of patients to
      ionizing radiation. For these latter reasons, multiparametric magnetic resonance
      imaging (MRI) is being increasingly used to characterize solid renal masses. The
      purpose of this manuscript is to review our imaging approach to solid renal
      masses in adults utilizing MRI with an emphasis on a multiparametric approach
      augmented by clinical data. 

PMID- 24446015
TI  - Sentinel node biopsy in papillary thyroid cancer--what is the potential?
AB  - PURPOSE: Sentinel node biopsy (SNB) may identify lymph node metastases in
      patients with papillary thyroid cancer (PTC), enabling selective application of
      central node dissection (CND). The aim of this study was to assess the
      feasibility of implementing SNB in patients undergoing thyroidectomy for a
      cytologically indeterminate/suspicious/malignant thyroid nodule and to determine
      the potential improvement in clinical outcomes and the costs associated with the
      SNB technique. METHODS: The treatment strategies and clinical and pathological
      outcomes of two retrospective cohorts of patients who underwent preoperative
      thyroid FNA over a 5-year period in two different centres were studied. The
      potential for implementing the SNB technique and the benefits and costs
      associated with implementation were estimated. RESULTS: In centre 1, in 819 adult
      patients who had thyroid fine-needle aspiration cytology, the final cytology was
      indeterminate, suspicious and diagnostic of malignancy in 113, 29 and 28
      patients, respectively. One hundred eight patients were 'suitable' for SNB.
      Twenty-three of these patients had PTC, six of whom underwent CND. Of these six
      patients, node metastasis was absent in five--the cohort in whom prophylactic CND
      may have been avoided consequent to a negative 'sentinel node' biopsy. Morbidity
      attributable to CND may have been avoided in up to four patients over a 5-year
      period. Costs associated with implementation of SNB outweighed any potential
      savings. Analysis of 491 patients in centre 2 confirmed that the benefit of SNB
      in PTC was similarly limited; morbidity attributable to CND may have been avoided
      in up to seven patients over a 5-year period. CONCLUSIONS: Even under ideal
      conditions (assuming 100 % node identification rate and 0 % false negative rate),
      the potential short- to medium-term benefit of sentinel node biopsy in patients
      with thyroid cancer in centres implementing a policy of selective or routine
      prophylactic CND is low.

PMID- 24446016
TI  - Use of 2940-nm Erbium-Yag fractional laser for treating the skin texture changes
      in stabilized Parry Romberg syndrome.

PMID- 24446017
TI  - Determination of chemical affinity of graphene oxide nanosheets with
      radionuclides investigated by macroscopic, spectroscopic and modeling techniques.
AB  - The chemical affinity of graphene oxide (GO) nanosheets with radionuclides
      (Eu(III) and U(VI)) was determined by macroscopic, spectroscopic and modeling
      techniques. The macroscopic results showed that the adsorption of Eu(III) and
      U(VI) on GO nanosheets was independent of ionic strength, indicating that inner
      sphere surface complexation predominated their adsorption. The maximum adsorption
      capacities calculated from a Langmuir model at pH 4.0 and T = 303 K were 208.33
      mg U(VI) and 28.70 mg Eu(III) per gram of GO nanosheets, respectively. No
      hysteresis was observed for both Eu(III) and U(VI) on GO nanosheets when
      desorption was initiated by lowering solution pH. While desorption was induced by
      replacing the radionuclide supernatant liquid with radionuclide-free electrolyte
      solution, the adsorption-desorption hysteresis was observed for U(VI) but not for
      Eu(III), indicating that the chemical affinity of GO nanosheets with U(vi) was
      stronger than that of GO nanosheets with Eu(III). The adsorption behaviors of
      Eu(III) and U(VI) on GO nanosheets can be fitted by a double diffuse layer
      surface complexation model with the mononuclear monodentate >SOM((n-1)+) and
      >SOMOH((n-2)+) complexes, and larger log K values of U(vi) was observed as
      compared to those of Eu(iii). According to the spectroscopic analysis, the
      irreversible adsorption of U(vi) on GO nanosheets at variable radionuclide
      concentrations was attributed to the oxygen-containing functional groups.

PMID- 24446018
TI  - Concussion among female middle-school soccer players.
AB  - IMPORTANCE: Despite recent increased awareness about sports concussions, little
      research has evaluated concussions among middle-school athletes. OBJECTIVES: To
      evaluate the frequency and duration of concussions in female youth soccer players
      and to determine if concussions result in stopping play and seeking medical care.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study from March 2008
      through May 2012 among 4 soccer clubs from the Puget Sound region of Washington
      State, involving 351 elite female soccer players, aged 11 to 14 years, from 33
      randomly selected youth soccer teams. Of the players contacted, 83.1%
      participated and 92.4% completed the study. MAIN OUTCOMES AND MEASURES:
      Concussion cumulative incidence, incidence rate, and description of the number,
      type, and duration of symptoms. We inquired weekly about concussion symptoms and,
      if present, the symptom type and duration, the event resulting in symptom onset,
      and whether the player sought medical attention or played while symptomatic.
      RESULTS: Among the 351 soccer players, there were 59 concussions with 43 742
      athletic exposure hours. Cumulative concussion incidence was 13.0% per season,
      and the incidence rate was 1.2 per 1000 athletic exposure hours (95% CI, 0.9
      1.6). Symptoms lasted a median of 4.0 days (mean, 9.4 days). Heading the ball
      accounted for 30.5% of concussions. Players with the following symptoms had a
      longer recover time than players without these symptoms: light sensitivity (16.0
      vs 3.0 days, P = .001), emotional lability (15.0 vs 3.5 days, P = .002), noise
      sensitivity (12.0 vs 3.0 days, P = .004), memory loss (9.0 vs 4.0 days, P = .04),
      nausea (9.0 vs 3.0 days, P = .02), and concentration problems (7.0 vs 2.0 days, P
      = .02). Most players (58.6%) continued to play with symptoms, with almost half
      (44.1%) seeking medical attention. CONCLUSIONS AND RELEVANCE: Concussion rates in
      young female soccer players are greater than those reported in older age groups,
      and most of those concussed report playing with symptoms. Heading the ball is a
      frequent precipitating event. Awareness of recommendations to not play and seek
      medical attention is lacking for this age group.

PMID- 24446019
TI  - Microwave conductivity of sorted CNT assemblies.
AB  - Recent progress with tailored growth and post-process sorting enables carbon
      nanotube (CNT) assemblies with predominantly metallic or semi-conducting
      concentrations. Cryogenic and microwave measurements performed here show
      transport dimensionality and overall order increasing with increasing metallic
      concentration, even in atmospheric doping conditions. By 120 GHz, the
      conductivity of predominantly semi-conducting assemblies grew to 400% its DC
      value at an increasing growth rate, while other concentrations a growth rate that
      tapered off. A generalized Drude model fits to the different frequency dependent
      behaviors and yields useful quality control parameters such as plasma frequency,
      mean free path, and degree of localization. As one of the first demonstrations of
      waveguides fabricated from this material, sorted CNTs from both as-made and post
      process sources were inserted into sections of practical micro-strip. With both
      sources, sorted CNT micro-strip increasingly outperformed the unsorted with
      increasing frequency-- illustrating that sorted CNT assemblies will be important
      for high frequency applications. 

PMID- 24446020
TI  - Acute haematogenous osteomyelitis in children.

PMID- 24446021
TI  - Secretory myoepithelial carcinoma: a histologic and molecular survey and a
      proposed nomenclature for mucin producing signet ring tumors.
AB  - Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary
      gland malignancy. While currently designated as an adenocarcinoma, myoepithelial
      differentiation has been implied in previously reported cases. We herein perform
      a survey of our cases of signet ring cell adenocarcinoma and review the
      literature in order to refine categorization of this rare tumor. Five cases were
      retrieved. One was reclassified as a mammary analogue secretory carcinoma,
      leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the
      presence of prominent signet ring or vacuolated cells arranged in islands,
      interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools
      of mucin. An extensive panel of histochemical and immunohistochemical stains and
      fluorescence in situ hybridization (FISH) (modeled after common phenotypes and
      molecular alterations seen in signet ring and myoepithelial tumors at other
      sites) was performed. The male-to-female ratio was 3:1. The mean age was 56 years
      (range 18-81). Sites involved included buccal mucosa (2), soft palate (1) and
      deep parotid (1). Perineural and angiolymphatic invasion were present in three
      and two cases respectively. One patient was lost to follow up and the remainder
      were alive and without disease at time of last follow up (mean 38 months). All
      cases showed mucicarmine positive vacuolated/signet ring cells embedded in a
      myxoid stroma. Three cases showed at least focal p63 staining and two cases
      showed positivity for calponin. Membranous E-cadherin was retained in all cases.
      FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases.
      Based on the current series and the previously reported cases, it is evident that
      signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and
      thus as a whole more appropriately designated as 'secretory myoepithelial
      carcinoma.' They behave in a fairly indolent fashion and do not share the major
      molecular alterations seen in other signet ring and myoepithelial tumor types. 

PMID- 24446023
TI  - Impact of programming strategies aimed at reducing nonessential implantable
      cardioverter defibrillator therapies on mortality: a systematic review and meta
      analysis.
AB  - BACKGROUND: Patients who receive implantable cardioverter defibrillator therapies
      are at higher risk of death versus those who do not. Programmed settings to
      reduce nonessential implantable cardioverter defibrillator therapies (therapy
      reduction programming) have been developed but may have adverse effects. This
      systematic review and meta-analysis assessed the relationship between therapy
      reduction programming with the risks of death from any cause, implantable
      cardioverter defibrillator shocks, and syncope. METHODS AND RESULTS: MEDLINE,
      EMBASE, and clinicaltrials.gov databases were searched to identify relevant
      studies. Those that followed patients for >=6 months and reported mortality were
      included. Six met the inclusion criteria; 4 randomized (Comparison of Empiric to
      Physician-Tailored Programming of ICDs [EMPIRIC], Multicenter Automatic
      Defibrillator Implantation Trial-Reduce Inappropriate Therapy [MADIT-RIT], Avoid
      Delivering Therapies for Non-sustained Arrhythmias in ICD Patients III [ADVANCE
      III], and Programming Implantable Cardioverter-Defibrillators in Patients with
      Primary Prevention Indication to Prolong Time to First Shock [PROVIDE]) and 2
      prospective studies (Role of Long Detection Window Programming in Patients With
      Left Ventricular Dysfunction, Non-ischemic Etiology in Primary Prevention Treated
      with a Biventricular ICD [RELEVANT] and Primary Prevention Parameters Evaluation
      [PREPARE]). These 6 studies included 7687 (3598 conventional and 4089 therapy
      reduction programming) patients. Most (77%) participants were men, had a history
      of ischemic heart disease (56%), and were prescribed beta-blockers (84%). Therapy
      reduction programming was associated with a 30% relative reduction in mortality
      (95% confidence interval, 16%-41%; P<0.001). No significant heterogeneity among
      studies was observed (P=0.6). A similar 26% reduction in mortality was observed
      when only the 4 randomized trials were included (95% confidence interval, 11%
      40%; P=0.002). These results were not significantly altered after adjustment for
      baseline characteristics. No significant difference in the risk of syncope was
      observed with conventional versus therapy reduction programming (P=0.5).
      CONCLUSIONS: Therapy reduction programming results in a large, significant, and
      consistent reduction in mortality, with no apparent increase in the risk of
      syncope.

PMID- 24446022
TI  - Incidence and significance of early recurrences of atrial fibrillation after
      cryoballoon ablation: insights from the multicenter Sustained Treatment of
      Paroxysmal Atrial Fibrillation (STOP AF) Trial.
AB  - BACKGROUND: Early recurrence of atrial fibrillation (ERAF) is common after
      radiofrequency catheter ablation for AF. We sought to determine the incidence and
      prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit
      of early reablation for ERAF after cryoballoon ablation is undetermined. METHODS
      AND RESULTS: The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF)
      trial randomized 245 patients with paroxysmal AF to medical therapy versus
      cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months.
      ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of
      follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds
      between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84
      patients experienced ERAF (51.5%). The only significant factor associated with
      ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03
      4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly
      related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among
      patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82-8.11;
      P<0.001) was associated with LR. Conversely, early reablation was associated with
      greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR,
      0.04; 95% CI, 0.01-0.32; P=0.002). CONCLUSIONS: ERAF after cryoballoon ablation
      occurs in ~50% of patients and is strongly associated with LR. Early reablation
      for ERAF is associated with excellent long-term freedom from recurrent AF.

PMID- 24446024
TI  - Time course of inflammation, myocardial injury, and prothrombotic response after
      radiofrequency catheter ablation for atrial fibrillation.
AB  - BACKGROUND: Inflammation has been linked to the genesis of stroke in atrial
      fibrillation (AF) and is implicated in early recurrent arrhythmia after AF
      ablation. We aimed to define the time course of inflammation, myocardial injury,
      and prothrombotic markers after radiofrequency ablation for AF and its relation
      to AF recurrence. METHODS AND RESULTS: Ninety consecutive AF patients (53%
      paroxysmal) undergoing radiofrequency ablation were recruited. High-sensitivity C
      reactive protein (hs-CRP), Troponin-T, creatine kinase-MB, fibrinogen, and D
      Dimer concentrations were measured at baseline, at 1, 2, 3, 7 days, and at 1
      month after ablation. AF recurrence was documented at 3 days and at 1, 3, and 6
      months follow-up. Troponin-T and creatine kinase-MB peaked at day 1 after
      procedure (both P<0.05). Hs-CRP peaked at day 3 after procedure (P<0.05).
      Fibrinogen (P<0.05) and D-Dimer (P<0.05) concentrations were significantly
      elevated at 1 week after procedure. Ln hs-CRP elevation correlated with Ln
      Troponin-T and fibrinogen elevation. The extent of Ln hs-CRP, Ln Troponin-T, and
      fibrinogen elevation predicted early AF recurrence within 3 days after procedure
      (P<0.05, respectively), but not at 3 and 6 months. CONCLUSIONS: Patients
      undergoing radiofrequency ablation for AF exhibit an inflammatory response within
      3 days. The extent of inflammatory response predicts early AF recurrence but not
      late recurrence. Prothrombotic markers are elevated at 1 week after ablation and
      may contribute to increased risk of early thrombotic events after AF ablation.

PMID- 24446025
TI  - Effect of radiofrequency catheter ablation for atrial fibrillation on morbidity
      and mortality: a nationwide cohort study and propensity score analysis.
AB  - BACKGROUND: This study examined the effect of radiofrequency catheter ablation
      (RFA) on reducing morbidity and mortality among patients with atrial fibrillation
      (AF). METHODS AND RESULTS: A retrospective cohort of patients with AF without
      prior stroke or heart failure (HF) who underwent RFA between 2003 and 2009 was
      identified using Taiwan's National Health Insurance claims database. Outpatients
      with AF who met the same enrollment criteria but did not receive RFA were matched
      (<=1:20) by hospitals and dates to serve as controls. Outcomes of interest were
      death, stroke, or hospitalization for HF. A proportional hazard Cox regression
      model adjusted by propensity scores (based on age, sex, hypertension, diabetes
      mellitus, comorbidities, medications, and medical resource utilization) was
      applied to estimate the hazard ratio and 95% confidence interval. A total of 846
      patients with AF who received RFA and 11 324 matched AF controls were included,
      with a mean follow-up of 3.74 and 3.96 years, respectively. RFA was associated
      with a lower hazard for stroke (hazard ratio, 0.57; 95% confidence interval, 0.35
      0.94; P=0.026). The reduction in the hazard for death and HF did not reach
      statistical significance (hazard ratio, 0.88; 95% confidence interval, 0.62-1.23;
      P=0.451 and hazard ratio, 0.78; 95% confidence interval, 0.55-1.12; P=0.185,
      respectively). Additional analysis using death as a competing risk showed similar
      results for stroke and HF. CONCLUSIONS: RFA did not reduce mortality or
      hospitalization for HF during the immediate 3.5-year follow-up. Although a
      beneficial effect on stroke prevention associated with RFA was suggested,
      residual confounding attributable to unmeasured factors remains a concern.

PMID- 24446026
TI  - A phase II study of cediranib as palliative treatment in patients with
      symptomatic malignant ascites or pleural effusion.
AB  - Malignant ascites and pleural effusion are challenging clinical problems, with a
      major impact on quality of life. We conducted a randomized phase II trial to
      assess the palliative value of cediranib, an oral vascular endothelial growth
      factor tyrosine kinase inhibitor (VEGF TKI). After a baseline paracentesis or
      thoracentesis (on day 0), patients with symptomatic malignant ascites and/or
      pleural effusion were randomized between immediate treatment with cediranib
      (Immediate Cediranib) or delayed treatment with cediranib (Delayed Cediranib) on
      day 29, or after a new puncture was needed. The primary objective of the study
      was the puncture-free survival, defined as the time from study start (day 1) to
      the first need for paracentesis or thoracentesis, or time to death, whichever
      event occurred first. Twelve patients were enrolled. The median puncture-free
      survival was 45 days (range 10-368) in the Immediate Cediranib patients and 7
      days (range 4-13) in the Delayed Cediranib patients (P = 0.011). The change in
      puncture-free interval (the puncture-free survival after study start minus the
      puncture-free interval before study start) increased with a median of 31 days in
      the Immediate Cediranib patients and shortened with a median of 3 days in the
      Delayed Cediranib patients (P = 0.015). The most common adverse events were
      fatigue and anorexia. In conclusion, cediranib increased the puncture-free
      survival and puncture-free interval with an acceptable toxicity profile. This is
      the first study in which an oral VEGFR TKI showed beneficial palliative effects
      in patients with malignant effusions. 

PMID- 24446027
TI  - Understanding the neuro-developmental pathogenesis of social disability: towards
      a cross-disorder approach.

PMID- 24446032
TI  - Fetal cardiac disease and fetal lung volume: an in utero MRI investigation.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) is a powerful, noninvasive tool to
      study fetal lung volumes after 18 weeks of gestation in vivo. In neonates with
      congenital heart disease (CHD), proper lung function is essential for postnatal
      survival. Antenatal detection of abnormal pulmonary development may help to
      optimize prenatal and perinatal management of at-risk fetuses. We aimed to
      investigate lung volumes in fetuses with prenatally diagnosed heart disease.
      METHODS: A cross-sectional, retrospective study of 105 consecutive singleton
      pregnancies with CHD and a control, non-CHD group (n = 115), that underwent fetal
      MRI was performed. The heart defects detected were divided into four groups. Lung
      volumes of fetuses with heart disease were compared with control, non-CHD
      fetuses. In addition, z-scores of lung volumes were calculated for the CHD group
      (normal range z-scores from -2-+2). RESULTS: As a group, fetuses with CHD have
      significantly smaller lung volumes compared with control fetuses when corrected
      by gestational age (GA) (p = 0.049). Of the 105 CHD fetuses studied, 18 had lung
      volumes with a z-score < -2. Fetuses with different types of CHD showed similar
      lung volumes. CONCLUSION: Our data indicate that postpartum pulmonary symptoms
      and outcome in neonates with congenital heart disease may be attributed to the
      cardiac disease itself and in part to smaller lung volumes.

PMID- 24446033
TI  - Switching plastic crystals of colloidal rods with electric fields.
AB  - When a crystal melts into a liquid both long-ranged positional and orientational
      order are lost, and long-time translational and rotational self-diffusion appear.
      Sometimes, these properties do not change at once, but in stages, allowing states
      of matter such as liquid crystals or plastic crystals with unique combinations of
      properties. Plastic crystals/glasses are characterized by long-ranged positional
      order/frozen-in-disorder but short-ranged orientational order, which is dynamic.
      Here we show by quantitative three-dimensional studies that charged rod-like
      colloidal particles form three-dimensional plastic crystals and glasses if their
      repulsions extend significantly beyond their length. These plastic phases can be
      reversibly switched to full crystals by an electric field. These new phases
      provide insight into the role of rotations in phase behaviour and could be useful
      for photonic applications. 

PMID- 24446034
TI  - Correlation of metabolic tumor volume and 11C-choline uptake with the pathology
      of prostate cancer: evaluation by use of simultaneously recorded MR and PET
      images.
AB  - PURPOSE: This study was conducted to assess the relationship between (11)C
      choline uptake and pathologic findings obtained by combined use of magnetic
      resonance (MR) and positron emission tomography (PET) imaging of patients with
      prostate cancer. MATERIALS AND METHODS: We retrospectively evaluated 69 patients
      with prostate cancer who underwent (11)C-choline PET-CT and magnetic resonance
      imaging before radical prostatectomy. Combined MR-PET images were acquired to
      obtain precise anatomic information. The maximum standardized uptake value
      (SUVmax) and metabolic tumor volume (MTV) were compared with pathologic findings
      from resected specimens as the reference standard. RESULTS: The mean and standard
      deviation of tumor SUVmax and MTV were 3.9 +/- 1.8 and 12.9 +/- 16.4,
      respectively. Tumors with high MTV (?8.2) were more likely to be admixed with
      prostatic intraepithelial neoplasia (PIN) (p < 0.0001) or hyperplasia (p <
      0.0001) in the background than those without these findings. Multiple regression
      analysis also revealed that the presence of hyperplasia (OR; 4.25, 95% CI 1.25
      14.4, p = 0.02) and PIN (OR; 9.22, 95% CI 2.60-32.7, p = 0.001) were associated
      with tumors with high MTV. CONCLUSION: We have demonstrated, by pathologic
      evaluation of patients with prostate cancer, that (11)C-choline uptake volume is
      greater for prostate cancer admixed with PIN and hyperplasia than that without.

PMID- 24446036
TI  - [Role of imaging modalities in the diagnosis of acute coronary syndrome (ACS):
      echocardiography, MRI, and CT].

PMID- 24446035
TI  - Clinicopathological and prognostic significance of EZH2 expression in upper
      urinary tract carcinoma.
AB  - Evidence suggests that overexpression of enhancer of zeste homologue 2 (EZH2) is
      associated with aggressive behavior in various cancers. However, the clinical,
      pathological, and prognostic associations of EZH2 expression in the upper urinary
      tract carcinoma have not been reported. This study aimed to investigate the
      significance of EZH2 expression in the upper urinary tract carcinoma by
      immunohistochemical analysis using a tissue microarray. High EZH2 expression was
      observed in 94 of 171 (55 %) cases and was significantly associated with several
      adverse prognostic factors, including sessile architecture, high histological
      grade, presence of lymphovascular invasion, concomitant carcinoma in situ, higher
      tumor stage, and higher Ki-67 expression (all P < 0.01). EZH2 expression status
      in primary and metastatic lesions was concordant in all 13 cases examined.
      Survival analyses were performed using the Kaplan-Meier method and multivariate
      Cox proportional hazards regression models. High EZH2 expression was
      significantly associated with a shorter metastasis-free survival (log-rank P =
      0.005; multivariate hazard ratio, 1.85; 95 % confidence interval, 0.93-3.71) and
      cancer-specific survival (log-rank P = 0.006; multivariate hazard ratio, 3.08; 95
      % confidence interval, 1.30-7.32) after nephroureterectomy. Our results suggest
      that EZH2 may serve as a novel prognostic biomarker and a potential therapeutic
      target in upper urinary tract carcinoma.

PMID- 24446037
TI  - [Antithrombotic treatment in acute coronary syndrome].

PMID- 24446038
TI  - [Interventional treatment in acute coronary syndrome].

PMID- 24446039
TI  - [Monitoring of anticoagulation--management in practice].

PMID- 24446040
TI  - [Acute coronary syndrome].

PMID- 24446041
TI  - [Myocardial infarction and cardiogenic shock].

PMID- 24446042
TI  - [Device therapy after acute coronary syndrome].
AB  - Acute coronary syndromes are seldom accompanied by high degree AV blocks.
      Implantation of a permanent pacemaker is rarely necessary.There is a high
      incidence of ventricular tachyarrhythmias during the acute phase of myocardial
      infarctions. Sustained VT or VF beyond 48 hours of the infarction indicate the
      need for an implantable cardioverter-defibrillator. If left ventricular ejecion
      fraction remains <=35 % for >40 days an ICD might be indicated for primary
      prophylaxis.If early after infarction a device implantation becomes necessary,
      biventricular stimulation should be used if ventricular pacing is necessary or
      LBBB with markedly increased QRS-duration is present.

PMID- 24446043
TI  - [New insights in pathogenesis and etiology of coronary artery disease].
AB  - In clinical practice the non-invasive diagnosis of "coronary heart disease" is
      based on the clinical findings, the detection of ischemia at rest or during
      exercise, and elevations of cardiac enzymes. However, due to the compensatory
      enlargement of the vessel diameter at the beginning of plaque growth, the so
      called Glagov effect, early stages of plaque development are missed by the
      angiography. By means of coronary angiography, changes of the coronary arteries
      become visible only in patients with angiographically recognizable lumen
      narrowing compared to the reference vessel segment. Thus, early or diffuse stages
      of atherosclerosis cannot be detected by ECG, stress-tests or coronary
      angiography. This limitation explains discrepancies, like positive troponin-test
      and even transmural ischemia, without angiographic visible coronary lumen
      narrowing. Diagnostic procedures such as intravascular ultrasound, optical
      coherence tomography, measurements of vasomotion and computed tomography can, in
      contrast, detect earlier stages of coronary artery disease and thus contribute to
      clarification in these patients. In addition, plaque rupture and plaque-erosion
      lead to acute or recurrent microembolism to distal myocardium with subsequent
      myocardial necrosis. In patients with formerly unexplained cardiovascular events,
      intravascular ultrasound, optical coherence tomography, and measurements of
      vasomotion help to understand the underlying pathophysiology. In the report after
      cardiac catheterization, the term "ruled out coronary heart disease" should be
      replaced by "No signs of obstructive coronary heart disease" and additional
      testing should be performed as necessary.

PMID- 24446044
TI  - [Peripheral artery disease as supplemental diagnosis in coronary heart disease-
      influence on diagnostics, treatment and prognosis].
AB  - Peripheral arterial disease (PAD) increases cardiovascular event rate in patients
      with coronary artery disease (CAD). Therefore PAD should be considered in
      patients with CAD with regard to diagnostic and therapeutic strategies. PAD may
      difficult diagnostic tests in CAD patients. Patients with PAD and CAD may be
      limited in stress testing by decreased leg perfusion. In addition, arterial
      puncture can be more difficult in sclerotic femoral arteries. Cardiovascular risk
      factors should be treated carefully in all manifestations of atherosclerosis.
      Target values from current guidelines are similar for PAD and CAD. Inhibitors of
      platelet aggregation are indication in both CAD and PAD. Exercise not only
      improves walking distance in patients with intermittent claudication but also
      improves cardiovascular prognosis in patients with atherosclerosis. 

PMID- 24446045
TI  - [Prevention after acute coronary syndrome].
AB  - Mortality is increased in acute coronary syndrome (ACS) related to the extent of
      myocardial injury even if percutaneous coronary intervention (PCI) was
      successful. The development of congestive heart failure (CHF) after PCI in ACS is
      of prognostic interest. Non-invasive imaging plays a major role for determination
      of structural myocardial damage and loss of function. Secondary prevention
      regarding pharmacologic and non-pharmacologic therapy is dependent on myocardial
      function and the presence or absence of CHF. Exercise training as part of the non
      pharmacological therapy plays an important role in rehabilitation after ACS
      according to the severity of injury. 

PMID- 24446046
TI  - [Diagnosis of acute coronary syndrome].
AB  - The acute coronary syndrome (ACS) is one of the most frequent differential
      diagnoses in emergency medicine. The causal mechanism of the ACS most often is an
      atherosclerotic plaque rupture. The differential diagnosis of ACS is guided by
      the clinical symptom of chest discomfort. The diagnosis is based on the
      electrocardiographic, biomarker and imaging findings before targeted therapy can
      be initiated. Over the last years we have witnessed breakthroughs in imaging
      techniques and the application of biomarkers such as highly sensitive or
      ultrasensitive cardiac troponin assays. They permit an early and sensitive
      diagnosis of ACS. Furthermore, they exhibit a high negative predictive value for
      a safe rule-out. Trained personnel and optimized structures in chest pain units
      constitute optimal conditions for a guideline conform therapy of patients with
      ACS. The number of certified chest pain units in Germany has constantly been
      increasing.

PMID- 24446047
TI  - Two novel mutations in the DSRAD gene in two Chinese pedigrees with
      dyschromatosis symmetrica hereditaria.
AB  - BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a highly penetrant
      autosomal dominant cutaneous disorder characterized by a mixture of
      hyperpigmented and hypopigmented macules localized on the back of the
      extremities. Genetic studies have identified pathogenic mutations in the double
      stranded RNA-specific adenosine deaminase (DSRAD) gene as responsible for this
      disorder. OBJECTIVES: To identify additional gene mutations of DSRAD in patients
      with DSH. METHODS: Two Chinese families with typical DSH were subjected to
      mutation detection in DSRAD. All DSRAD exons and their flanking intronic
      sequences were amplified and sequenced. RESULTS: Two novel mutations in the
      functional domains of the DSRAD gene were identified in two pedigrees. The c.
      3140G>A(p.G1047D) mutation was found in all patients but not in the healthy
      individuals from the same family (I) and c.1760 A>G(p.Y587C) mutation was found
      in all the patients but not in the healthy family members (II). CONCLUSIONS: Two
      novel DSRAD mutations, p.G1047D and p.Y587C, were found in Chinese patients with
      DSH and our data add new variants to the knowledge of DSRAD mutations in DSH.

PMID- 24446048
TI  - Engagement, peer production, and the learning healthcare system.

PMID- 24446049
TI  - Addressing the particular recordkeeping needs of infertile Orthodox Jewish
      couples considering the use of donated eggs.
AB  - Infertility counseling is a specialized field that will continue to grow in
      coming years as the impact of infertility and its treatment is documented more
      and more in terms of emotional, physical, social and life consequences.
      Counselors should anticipate issues that may arise in the future and assist
      couples in their efforts to address them. We report here on recordkeeping issues
      of possible future concern that should be addressed when Orthodox Jewish couples
      make use of donor eggs. Good medical practice values the importance of
      understanding the patient's individual concerns and values, including the complex
      psychological, sociological and cultural context in which they experience their
      infertility. Good counseling anticipates and addresses future problems about
      which patients might not currently be aware. 

PMID- 24446051
TI  - Unprecedented bistability domain and interplay between spin crossover and
      polymorphism in a mononuclear iron(II) complex.
AB  - A mononuclear complex, [FeL2](BF4)2.xH2O (1LS?xH2O), where L is 4-(3,5-dimethyl
      1H-pyrazol-1-yl)-2-(pyridin-2-yl)-6-methylpyrimidine, can be converted into
      several phases showing different spin crossover regimes. In the first heating
      1LS?xH2O loses water molecules and converts into a mixture of two high spin
      phases, 1A/HS and 1C/HS. Further cycling produces the low spin phase 1A/LS. The
      transition 1A/LS<->1A/HS is accompanied by a 130 K wide hysteresis loop (Tc? =
      490 K, Tc? = 360 K). Annealing the complex 1LS?xH2O at 500 K yields a high spin
      phase 1C/HS. The phase 1C/HS undergoes spin conversion to the corresponding low
      spin phase 1C/LS on cooling, T1/2 ~ 320 K. Dehydration of 1LS?xH2O at 370 or 400
      K yields a certain low spin phase, 1X/LS, which irreversibly transforms into a
      high spin phase 1B/HS, which, in turn, reversibly transforms to the low spin
      phase 1B/LS on cooling, T1/2 ~ 320 K.

PMID- 24446050
TI  - Long-term influence of biochar on native organic carbon mineralisation in a low
      carbon clayey soil.
AB  - Biochar can influence native soil organic carbon (SOC) mineralisation through
      "priming effects". However, the long-term direction, persistence and extent of
      SOC priming by biochar remain uncertain. Using natural (13)C abundance and under
      controlled laboratory conditions, we show that biochar-stimulated SOC
      mineralisation ("positive priming") caused a loss of 4 to 44 mg C g(-1) SOC over
      2.3 years in a clayey, unplanted soil (0.42% OC). Positive priming was greater
      for manure-based or 400 degrees C biochars, cf. plant-based or 550 degrees C
      biochars, but was trivial relative to recalcitrant C in biochar. From 2.3 to 5.0
      years, the amount of positively-primed soil CO2-C in the biochar treatments
      decreased by 4 to 7 mg C g(-1) SOC. We conclude that biochar stimulates native
      SOC mineralisation in the low-C clayey soil but that this effect decreases with
      time, possibly due to depletion of labile SOC from initial positive priming,
      and/or stabilisation of SOC caused by biochar-induced organo-mineral
      interactions. 

PMID- 24446053
TI  - Model-based selection of areas for the restoration of Acrocephalus paludicola
      habitats in NE Germany.
AB  - The global Aquatic Warbler (Acrocephalus paludicola, Vieillot, 1817) population
      has suffered a major decline due to the large-scale destruction of its natural
      habitat (fen mires). The species is at risk of extinction, especially in NE
      Germany/NW Poland. In this study, we developed habitat suitability models based
      on satellite and environmental data to identify potential areas for habitat
      restoration on which further surveys and planning should be focused. To create a
      reliable model, we used all Aquatic Warbler presences in the study area since
      1990 as well as additional potentially suitable habitats identified in the field.
      We combined the presence/absence regression tree algorithm Cubist with the
      presence-only algorithm Maxent since both commonly outperform other algorithms.
      To integrate the separate model results, we present a new way to create a
      metamodel using the initial model results as variables. Additionally, a histogram
      approach was applied to further reduce the final search area to the most
      promising sites. Accuracy increased when using both remote sensing and
      environmental data. It was highest for the integrated metamodel (Cohen's Kappa of
      0.4, P < 0.001). The final result of this study supports the selection of the
      most promising sites for Aquatic Warbler habitat restoration. 

PMID- 24446054
TI  - Toward a cultural-historical perspective on the selection task.
AB  - Independently of their age, individuals produce weak logical responses when they
      solve the Wason selection task. Many studies describe conditional reasoning,
      focusing on intra-individual and general processes. The role of meaning
      attributed to the situation or the linguistic interpretation of the rules have
      nevertheless been stressed by pragmatic studies. Few scattered studies show the
      role of collective situations, of subjects' prior knowledge and of objects in
      solving the selection task. This paper goes back to the questions raised by the
      selection task and attempts to place past results into a cultural-historical
      theoretical framework, which defines a complex and evolving cognitive system,
      where human beings rely on social exchanges, equip themselves with cultural
      instruments, create intellectual tools, and give meaning to their experiences.
      Taking into account such a system is necessary to shed light upon the
      possibilities for the development of human thinking processes in order to solve
      selection tasks. 

PMID- 24446055
TI  - 99Tc NMR as a promising technique for structural investigation of biomolecules:
      theoretical studies on the solvent and thermal effects of phenylbenzothiazole
      complex.
AB  - The phenylbenzothiazole compounds show antitumor properties and are highly
      selective. In this paper, the (99)Tc chemical shifts based on the ((99m)Tc)(CO)3
      (NNO) complex conjugated to the antitumor agent 2-(4'-aminophenyl)benzothiazole
      are reported. Thermal and solvent effects were studied computationally by quantum
      chemical methods, using the density functional theory (DFT) (DFT level BPW91/aug
      cc-pVTZ for the Tc and BPW91/IGLO-II for the other atoms) to compute the NMR
      parameters for the complex. We have calculated the (99)Tc NMR chemical shifts of
      the complex in gas phase and solution using different solvation models
      (polarizable continuum model and explicit solvation). To evaluate the thermal
      effect, molecular dynamics simulations were carried, using the atom-centered
      density matrix propagation method at the DFT level (BP86/LanL2dz). The results
      highlight that the (99)Tc NMR spectroscopy can be a promising technique for
      structural investigation of biomolecules, at the molecular level, in different
      environments.

PMID- 24446056
TI  - Texas hospital sued for keeping pregnant woman on life support despite family's
      objections.

PMID- 24446057
TI  - Major contribution of the medial amygdala to hypertension in BPH/2J genetically
      hypertensive mice.
AB  - BPH/2J mice are recognized as a neurogenic model of hypertension primarily based
      on overactivity of the sympathetic nervous system and greater neuronal activity
      in key autonomic cardiovascular regulatory brain regions. The medial amygdala
      (MeAm) is a forebrain region that integrates the autonomic response to stress and
      is the only region found to have greater Fos during the night and daytime in
      BPH/2J compared with BPN/3J mice. To determine the contribution of the MeAm to
      hypertension, the effect of neuronal ablation on blood pressure (BP) was assessed
      in BPH/2J (n=7) and normotensive BPN/3J mice (n=7). Mice were preimplanted with
      radiotelemetry devices to measure 24-hour BP and cardiovascular responses to
      stress, before and 1 to 3 weeks after bilateral lesions of the MeAm. Baseline BP
      was 121+/-4 mm Hg in BPH/2J and 101+/-2 mm Hg in BPN/3J mice (Pstrain<0.001).
      MeAm lesions reduced BP by 11+/-2 mm Hg in BPH/2J mice (Plesion<0.001) but had no
      effect in BPN/3J mice. The hypotensive effect of lesions in BPH/2J mice was
      similar during both day and night, suggesting that the MeAm has tonic effects on
      BP, but the pressor response to stress was maintained in both strains.
      Midfrequency BP power was attenuated in both strains (Plesion<0.05) and the
      depressor responses to pentolinium after enalaprilat pretreatment was attenuated
      after lesions in BPH/2J mice (Plesion<0.001; n=3). These findings indicate that
      the MeAm provides a tonic contribution to hypertension in BPH/2J mice, which is
      independent of its role in stress reactivity or circadian BP influences. 

PMID- 24446058
TI  - Inhibition of mammalian target of rapamycin with rapamycin reverses hypertrophic
      cardiomyopathy in mice with cardiomyocyte-specific knockout of PTEN.
AB  - The role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) in
      the maintenance of cardiac homeostasis still remains controversial. This study
      was designed to evaluate the role of cardiomyocyte-specific PTEN in the
      maintenance of cardiac homeostasis and the underlying mechanisms involved with a
      focus on autophagy, an evolutionarily conserved pathway for protein degradation.
      Cardiomyocyte-specific PTEN((flox/flox))/alpha-myosin heavy chain Cre mice,
      henceforth referred to as CM-PTENKO, were generated by crossing the floxed PTEN
      mice with alpha-myosin heavy chain Cre mice driven by a Cre recombinase promoter.
      The adult PTEN(-/-) mice displayed the phenotype of established hypertrophic
      cardiomyopathy, including unfavorable geometric, functional, and histological
      changes. Furthermore, cardiomyocyte-specific PTEN knockout mice exhibited
      increased cardiac mammalian target of rapamycin although suppressed autophagy.
      Treatment with rapamycin (2 mg/kg per day, IP), an inhibitor of mammalian target
      of rapamycin, for 1 month effectively reversed the established hypertrophic
      cardiomyopathy in CM-PTENKO mice. With rapamycin treatment, autophagy activity
      was significantly restored in the heart of CM-PTENKO mice. Taken together, our
      results demonstrate an essential role for cardiomyocyte PTEN in maintaining
      cardiac homeostasis under physiological condition. Cardiomyocyte-specific
      deletion of PTEN results in the development of hypertrophic cardiomyopathy
      possibly through a mechanism associated with mammalian target of rapamycin
      hyperactivation and autophagy suppression. 

PMID- 24446059
TI  - Bidirectional adherence changes and associated factors in patients switched from
      free combinations to equivalent single-pill combinations of antihypertensive
      drugs.
AB  - There are no reported studies assessing the effects of fixed-dose single-pill
      combinations (SPCs) of antihypertensive drugs on adherence in real-world patients
      with hypertension switched from free combinations to the corresponding SPCs. In
      this retrospective cohort study with a 1-year mirror-image design, a total of 896
      patients who had been prescribed with an angiotensin-converting enzyme inhibitor
      or angiotensin receptor blocker and a thiazide-type diuretic within the preceding
      12 months of the index (switching) date and the corresponding SPC within 12
      months after the index date were included by using the Taiwan National Health
      Insurance database from January 2001 to December 2007. Adherence was measured by
      medication possession ratio (MPR). For patients switched to SPCs, the MPR
      increased significantly from 42% in the preindex period to 69% in the postindex
      period (relative difference, 75%; 95% confidence interval, 58%-100%; P<0.001).
      However, for switched patients with high adherence (MPR >=0.8) in the preindex
      period, the MPR unexpectedly decreased in the postindex period (absolute
      difference, -13%; 95% confidence interval, -17% to -9%; P<0.001). In multivariate
      analysis, MPR difference was inversely related to the preindex MPR, the number of
      other antihypertensive drugs, and congestive heart failure. In summary, despite
      of the dramatic effect of SPCs on improving adherence, this strategy is not
      effective or even worse in patients adequately adhering to their free-combined
      antihypertensive regimens. The inverse association between adherence improvement
      and number of concurrent antihypertensive drugs suggests early use of SPCs to
      curtail the nonadherence gap. 

PMID- 24446060
TI  - Characterization of antibody specificities associated with preeclampsia.
AB  - The presence of maternal autoantibodies has been previously associated with
      preeclampsia, although the composition of the antibody repertoire in preeclampsia
      has not been well characterized. Given this, we applied a bacterial display
      peptide library to identify peptides that preferentially react with plasma
      antibodies from patients with preeclampsia (n=15) versus healthy-outcome
      pregnancies (n=18). Screening using fluorescence-activated cell sorting
      identified 38 peptides that preferentially bind to antibodies from individuals
      with preeclampsia. These preeclampsia-specific peptides possessed similar motifs
      of R(G)/S(G)/-WW(G)/S, RWW(G)/S, or WGWGXX(R)/K distinct from the angiotensin II
      type 1 receptor epitope AFHYESQ. Seven library-isolated peptides and a cell
      surface-displayed angiotensin II type 1 receptor epitope were used to construct a
      diagnostic algorithm with a training set of 18 new preeclamptic and 22 healthy
      outcome samples from geographically distinct cohorts. Cross-validation within the
      training group resulted in averaged areas underneath a receiver operating
      characteristic curve of 0.78 and 0.72 with and without the known receptor
      epitope, respectively. In a small validation set (12 preeclamptic; 8 healthy),
      the algorithm consisting only of library-isolated peptides correctly classified
      10 preeclamptic and 6 healthy samples using a predefined cutoff that achieved 61%
      sensitivity (95% confidence interval, 36%-83%) at 95% specificity (95% confidence
      interval, 77%-100%) in training set (n=40) cross-validation. Our results indicate
      that antibodies with specificities other than anti-angiotensin II type 1 receptor
      are prevalent in preeclampsia patients and may be useful as diagnostic
      biomarkers. 

PMID- 24446061
TI  - Angiotensin-converting enzyme 2-independent action of presumed angiotensin
      converting enzyme 2 activators: studies in vivo, ex vivo, and in vitro.
AB  - Angiotensin (Ang)-converting enzyme 2 (ACE2) is a key enzyme in the metabolism of
      Ang II. XNT (1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4
      methylphenyl) sulfonyl oxy]-9H-xanthene-9-one) and diminazene have been reported
      to exert various organ-protective effects, which are attributed to the activation
      of ACE2. To test the effect of these compounds, we studied Ang II degradation in
      vivo and in vitro as well as their effect on ACE2 activity in vivo and in vitro.
      In a model of Ang II-induced acute hypertension, blood pressure (BP) recovery was
      markedly enhanced by XNT (slope with XNT, -3.26+/-0.2 versus -1.6+/-0.2 mm Hg/min
      without XNT; P<0.01). After Ang II infusion, neither plasma nor kidney ACE2
      activity was affected by XNT. Plasma Ang II and Ang (1-7) levels also were not
      significantly affected by XNT. The BP-lowering effect of XNT seen in wild-type
      animals was also observed in ACE2 knockout mice (slope with XNT, -3.09+/-0.30
      versus -1.28+/-0.22 mm Hg/min without XNT; P<0.001). These findings show that the
      BP-lowering effect of XNT in Ang II-induced hypertension cannot be because of the
      activation of ACE2. In vitro and ex vivo experiments in both mice and rat kidney
      confirmed a lack of enhancement of ACE2 enzymatic activity by XNT and diminazene.
      Moreover, Ang II degradation in vitro and ex vivo was unaffected by XNT and
      diminazene. We conclude that the biological effects of these compounds are ACE2
      independent and should not be attributed to the activation of this enzyme. 

PMID- 24446062
TI  - Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin
      inhibitor, in Asian patients with hypertension: a randomized, double-blind,
      placebo-controlled study.
AB  - LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in
      class angiotensin receptor neprilysin inhibitor, concomitantly inhibits
      neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind,
      placebo-controlled study, the first in Asia for this drug, evaluated the dose
      related efficacy and safety of LCZ696 in patients with hypertension using 24-hour
      ambulatory blood pressure (BP) monitoring. Asian patients aged >=18 years (n=389)
      with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg
      (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was
      mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus
      placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy
      variables included changes in clinic systolic BP and pulse pressure and changes
      in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety
      assessments included recording all adverse events and serious adverse events. A
      total of 362 patients completed the study. Reductions in clinic systolic BP,
      diastolic BP (P<0.0001), and pulse pressure (P<0.001) were significantly greater
      with all doses of LCZ696 than with placebo. There were also significant
      reductions in 24-hour, daytime, and nighttime ambulatory systolic BP, diastolic
      BP, and pulse pressure for all doses of LCZ696 compared with placebo (P<0.0001).
      LCZ696 was well tolerated, and no cases of angioedema were reported. In
      conclusion, LCZ696 is effective for the treatment of hypertension in Asian
      population and, in general, is safe and well tolerated. Clinical Trial
      Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101. 

PMID- 24446063
TI  - Features of cardiac remodeling, associated with blood pressure and fibrosis
      biomarkers, are frequent in subjects with abdominal obesity.
AB  - Incidence and prevalence of abdominal obesity (AO) are growing exponentially.
      Subjects with AO are at higher risk of developing heart failure. The purpose of
      the study was to investigate early changes in cardiac and arterial structure and
      function and extracellular matrix biomarkers in normotensive healthy subjects
      with AO. Subjects with AO and age- and sex-matched controls underwent
      echocardiography, MRI (cardiac remodeling index), carotid intima-media thickness,
      pulse wave velocity, and blood fibrosis biomarkers measurements. We enrolled 87
      subjects with AO and 53 controls. Although normotensive, subjects with AO had
      higher systolic blood pressure (BP; 122+/-11 versus 116+/-11 mm Hg; P=0.003),
      left ventricular mass (94+/-24 versus 84+/-21 g; P=0.034), and cardiac remodeling
      index (0.67+/-0.16 versus 0.60+/-0.10 g/mL; P=0.026) but unchanged carotid intima
      media thickness and pulse wave velocity. Diastolic dysfunction (E' <10 cm/s)
      could be detected in 38% of subjects with AO (4% in controls). Left ventricular
      remodeling, as assessed by cardiac remodeling index, was positively and
      independently associated with higher BP (systolic BP and mean arterial pressure
      but not diastolic BP) and AO. Higher BP, AO, and procollagen-III-N-terminal
      peptide (>=2.4 ng/mL) concentrations (odds ratio, 4.15 [1.42-12.2]; P=0.01) were
      positively associated with diastolic dysfunction. Early cardiac structural
      remodeling, fibrosis, and diastolic dysfunction were detectable in healthy
      subjects with AO. Higher BP, procollagen-III-N-terminal peptide, and AO were
      independently associated with early cardiac structural and functional changes. It
      is to be investigated whether in subjects with AO, an early BP reduction, even if
      normotensive, combined with weight loss may avoid adverse cardiac remodeling and
      protect against progression to heart failure. 

PMID- 24446064
TI  - Prostaglandin E2 mediates connecting tubule glomerular feedback.

PMID- 24446065
TI  - Microbial diversity in Los Azufres geothermal field (Michoacan, Mexico) and
      isolation of representative sulfate and sulfur reducers.
AB  - Los Azufres spa consists of a hydrothermal spring system in the Mexican Volcanic
      Axis. Five samples (two microbial mats, two mud pools and one cenote water),
      characterized by high acidity (pH between 1 and 3) and temperatures varying from
      27 to 87  degrees C, were investigated for their microbial diversity by Terminal
      Restriction Fragment Length Polymorphism (T-RFLP) and 16S rRNA gene library
      analyses. These data are the first to describe microbial diversity from Los
      Azufres geothermal belt. The data obtained from both approaches suggested a low
      bacterial diversity in all five samples. Despite their proximity, the sampling
      points differed by their physico-chemical conditions (mainly temperature and
      matrix type) and thus exhibited different dominant bacterial populations:
      anoxygenic phototrophs related to the genus Rhodobacter in the biomats, colorless
      sulfur oxidizers Acidithiobacillus sp. in the warm mud and water samples, and
      Lyzobacter sp.-related populations in the hot mud sample (87  degrees C).
      Molecular data also allowed the detection of sulfate and sulfur reducers related
      to Thermodesulfobium and Desulfurella genera. Several strains affiliated to both
      genera were enriched or isolated from the mesophilic mud sample. A feature common
      to all samples was the dominance of bacteria involved in sulfur and iron
      biogeochemical cycles (Rhodobacter, Acidithiobacillus, Thiomonas, Desulfurella
      and Thermodesulfobium genera). 

PMID- 24446066
TI  - Cellular and molecular stimulation of adipose-derived stem cells under hypoxia.
AB  - Cultivation under hypoxia has beneficial effects on adipose-derived stem cells
      (ASCs). Despite a history of extensive research on the responses of ASCs to
      hypoxia, investigations have focused on functional alterations of ASCs.
      Therefore, we provide novel insight in this review into the cellular and
      molecular changes that occur in ASCs under hypoxic conditions. Hypoxia increases
      the proliferation and migration of ASCs by the generation of reactive oxygen
      species (ROS) and downstream phosphorylation of platelet-derived growth factor
      receptor-beta, ERK1/2, and Akt. Chronically, activation of these signaling
      pathways upregulates miR-210 via phosphorylation of NF-kappaB and Elk1. Protein
      tyrosine phosphatase, non-receptor type 2 (PTPN2) is a direct miR-210 target, and
      downregulation of PTPN2 mediates the proliferation and migration of ASCs during
      hypoxia. In addition, the paracrine effect of ASCs is enhanced under hypoxic
      conditions, irrespective of whether ROS are generated. Hypoxic preconditioning
      stabilizes hypoxia inducible factor-1alpha under hypoxic conditions and increases
      secretion of vascular endothelial growth factor, thereby improving the
      regenerative potential of ASCs. Therefore, understanding the cellular and
      molecular changes that occur during hypoxia is highly relevant for the
      development of novel ASC therapies. 

PMID- 24446067
TI  - Rhodium(I)-catalyzed decarbonylative spirocyclization through C-C bond cleavage
      of benzocyclobutenones: an efficient approach to functionalized spirocycles.
AB  - The rhodium-catalyzed formation of all-carbon spirocenters involves a
      decarbonylative coupling of trisubstituted cyclic olefins and benzocyclobutenones
      through C?C activation. The metal-ligand combination [{Rh(CO)2 Cl}2 ]/P(C6 F5 )3
      catalyzed this transformation most efficiently. A range of diverse spirocycles
      were synthesized in good to excellent yields and many sensitive functional groups
      were tolerated. A mechanistic study supports a hydrogen-transfer process that
      occurs through a beta-H elimination/decarbonylation pathway. 

PMID- 24446068
TI  - Clinicopathological features of 25 patients with acquired perforating dermatosis.
AB  - BACKGROUND: Acquired perforating dermatosis (APD) is a rare group of skin
      disorders characterized by transepidermal elimination of dermal tissue material.
      There are only a few studies of APD. OBJECTIVE: We aimed to review the
      clinicopathologic features of patients with APD and evaluate the outcomes of
      treatments. MATERIAL AND METHODS: The medical records of 25 patients who were
      clinically and histopathologically diagnosed as having APD between 2006 and 2013
      were retrospectively reviewed. The histopathologic sections and the results of
      elastic, trichrome and periodic acid Shiff (PAS) staining were evaluated.
      RESULTS: Of the patients, 17 (68%) had ARPC, 7 (28%) had perforating
      folliculitis, 1 (4%) had Kyrle's disease. Male/female ratio was 1.3. The mean age
      was 51.8 +/- 12.8 years. The disease duration ranged between 15 days and 96
      months. Diabetes mellitus was the most common disease associated with APD (48%).
      The walls of vessels were PAS positive in the lesions of 6 of 13 diabetic
      patients. After various treatments, almost all lesions regressed in 15 (60%)
      patients. CONCLUSION: Acquired perforating dermatosis may present with various
      clinical features and is mostly associated with diabetes mellitus. Diabetes
      mellitus may be involved in the pathogenesis of APD via microangiopathy and other
      mechanisms.

PMID- 24446069
TI  - Exendin-4 attenuates endoplasmic reticulum stress through a SIRT1-dependent
      mechanism.
AB  - Accumulation of excess hepatic lipids contributes to insulin resistance and liver
      disease associated with endoplasmic reticulum (ER) stress. Exendin-4 is an
      agonist of the glucagon-like peptide 1 receptor and plays a role in improving
      insulin resistance and liver disease by increasing silent mating type information
      regulation 2 homolog (SIRT) 1. However, the effects and mechanism of action of
      exendin-4 on responses to palmitic acid (PA)-induced ER stress in hepatocytes
      have not been clearly defined. We investigated whether exendin-4 attenuates PA
      induced ER stress via SIRT1 in HepG2 cells. PA treatment induced increased
      expression of PRKR-like endoplasmic reticulum kinase, inositol-requiring kinase
      1alpha (IRE1alpha), activating transcription factor 6 (ATF6), and C/EBP
      homologous protein (CHOP) mRNA. Exendin-4 decreased the expression of P
      IRE1alpha, ATF6, X-box binding protein-1 and CHOP, and increased the expression
      of SERCA2b. A significant decrease in the hepatic expression of PUMA, BAX,
      cytochrome c, and cleaved caspase-3 were observed in hepatocytes treated with
      exendin-4. The TUNEL assay consistently showed that exendin-4 reversed hepatocyte
      apoptosis induced by treatment with PA. Inhibition of SIRT1 by nicotinamide and
      siRNA significantly increased the expression of ER stress marker genes in cells
      treated with both PA and exendin-4. In conclusion, increased SIRT1 by exendin-4
      attenuates PA-induced ER stress and mitochondrial dysfunction in hepatocytes.

PMID- 24446071
TI  - What is the relationship between soil methane oxidation and other C compounds?

PMID- 24446070
TI  - An intron-containing, heat-inducible stress-70 gene in the millipede
      Tachypodoiulus niger (Julidae, Diplopoda).
AB  - The highly conserved part of the nucleotide-binding domain of the hsp70 gene
      family was amplified from the soil diplopod Tachypodoiulus niger (Julidae,
      Diplopoda). Genomic DNA yielded 701, 549 and 540 bp sequences, whereas cDNA from
      heat shocked animals produced only one distinct fragment of 543 bp. The sequences
      could be classified as a 70 kDa heat shock protein (hsp70), the corresponding 70
      kDa heat shock cognate (hsc70) and a glucose-related hsp70 homologue (grp78).
      Comparisons of genomic and cDNA sequences of hsc70 identified two introns within
      the consensus sequence. Generally, stress-70 expression levels were low, which
      hampered successful RT-PCR and subsequent subcloning. Following experimental heat
      shock, however, the spliced hsc70 was amplified predominantly, instead of its
      inducible homologue hsp70. This finding suggests that microevolution in this soil
      dwelling arthropod is directed towards low constitutive stress-70 levels and that
      the capacity for stress-70 induction presumably is limited. hsc70, albeit having
      introns, apparently is inducible and contributes to the stress-70 response.

PMID- 24446072
TI  - Bayesian modeling of cost-effectiveness studies with unmeasured confounding: a
      simulation study.
AB  - Unmeasured confounding is a common problem in observational studies. Failing to
      account for unmeasured confounding can result in biased point estimators and poor
      performance of hypothesis tests and interval estimators. We provide examples of
      the impacts of unmeasured confounding on cost-effectiveness analyses using
      observational data along with a Bayesian approach to correct estimation. Assuming
      validation data are available, we propose a Bayesian approach to correct cost
      effectiveness studies for unmeasured confounding. We consider the cases where
      both cost and effectiveness are assumed to have a normal distribution and when
      costs are gamma distributed and effectiveness is normally distributed. Simulation
      studies were conducted to determine the impact of ignoring the unmeasured
      confounder and to determine the size of the validation data required to obtain
      valid inferences.

PMID- 24446073
TI  - Erratum to: Onset-related differences in neural substrates of tinnitus-related
      distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal
      cortex in early-onset tinnitus.

PMID- 24446074
TI  - Persistent changes in neuronal structure and synaptic plasticity caused by proton
      irradiation.
AB  - Cranial radiotherapy is used routinely to control the growth of primary and
      secondary brain tumors, but often results in serious and debilitating cognitive
      dysfunction. In part due to the beneficial dose depth distributions that may
      spare normal tissue damage, the use of protons to treat CNS and other tumor types
      is rapidly gaining popularity. Astronauts exposed to lower doses of protons in
      the space radiation environment are also at risk for developing adverse CNS
      complications. To explore the consequences of whole body proton irradiation, mice
      were subjected to 0.1 and 1 Gy and analyzed for morphometric changes in
      hippocampal neurons 10 and 30 days following exposure. Significant dose-dependent
      reductions (~33 %) in dendritic complexity were found, when dendritic length,
      branching and area were analyzed 30 days after exposure. At equivalent doses and
      times, significant reductions in the number (~30 %) and density (50-75 %) of
      dendritic spines along hippocampal neurons of the dentate gyrus were also
      observed. Immature spines (filopodia, long) exhibited the greatest sensitivity
      (1.5- to 3-fold) to irradiation, while more mature spines (mushroom) were more
      resistant to changes over a 1-month post-irradiation timeframe. Irradiated
      granule cell neurons spanning the subfields of the dentate gyrus showed
      significant and dose-responsive reductions in synaptophysin expression, while the
      expression of postsynaptic density protein (PSD-95) was increased significantly.
      These findings corroborate our past work using photon irradiation, and
      demonstrate for the first time, dose-responsive changes in dendritic complexity,
      spine density and morphology and synaptic protein levels following exposure to
      low-dose whole body proton irradiation. 

PMID- 24446075
TI  - Combining in silico and in cerebro approaches for virtual screening and pose
      prediction in SAMPL4.
AB  - The SAMPL challenges provide an ideal opportunity for unbiased evaluation and
      comparison of different approaches used in computational drug design. During the
      fourth round of this SAMPL challenge, we participated in the virtual screening
      and binding pose prediction on inhibitors targeting the HIV-1 integrase enzyme.
      For virtual screening, we used well known and widely used in silico methods
      combined with personal in cerebro insights and experience. Regular docking only
      performed slightly better than random selection, but the performance was
      significantly improved upon incorporation of additional filters based on
      pharmacophore queries and electrostatic similarities. The best performance was
      achieved when logical selection was added. For the pose prediction, we utilized a
      similar consensus approach that amalgamated the results of the Glide-XP docking
      with structural knowledge and rescoring. The pose prediction results revealed
      that docking displayed reasonable performance in predicting the binding poses.
      However, prediction performance can be improved utilizing scientific experience
      and rescoring approaches. In both the virtual screening and pose prediction
      challenges, the top performance was achieved by our approaches. Here we describe
      the methods and strategies used in our approaches and discuss the rationale of
      their performances. 

PMID- 24446076
TI  - Treatment of weight regain following roux-en-Y gastric bypass: revision of pouch,
      creation of new gastrojejunostomy and placement of proximal pericardial patch
      ring.
AB  - In the literature, weight regain or failure of weight loss has been reported in
      up to 35% of patients after Roux-en-Y gastric bypass (RYGB). Several revisional
      procedures have been suggested to reinitiate further weight loss in this group of
      patients, and placing a silastic ring around the pouch proximal to the
      gastrojejunostomy is one among those procedures. The aim of our study is to
      evaluate and compare the safety and efficacy of salvage banding using a
      pericardial patch after RYGB for further weight loss. Between December 2009 and
      April 2013, a total of 46 patients underwent revision with pericardial patch ring
      after RYGB for weight regain/failure of weight loss. A retrospective review of a
      prospectively collected database was performed, noting the outcomes and
      complications of the procedure. The mean body mass index at the time of revision
      was 40.1 +/- 6.8 kg/m2. Mean percentage of excess weight loss was 23.4 +/- 15.7%,
      39.0 +/- 27.4%, and 18.9 +/- 20.5% at 6, 12 and 24 months after revision,
      respectively. Eight (17.4%) patients required a total of 11 readmissions due to
      nausea, vomiting, dysphagia and abdominal pain. Six (13.0%) patients underwent a
      total of six reoperations, including four patients with laparoscopic removal of
      the pericardial patch and another revision of RYGB, and two patients with repair
      of perforated ulcers. Revision with pericardial patch ring after gastric bypass
      for weight regain or failure of weight loss may not be feasible, safe and
      effective.

PMID- 24446077
TI  - [7th revision of the declaration of Helsinki: more than a recommendation?].

PMID- 24446078
TI  - Economic burden of time lost due to injury in NHL hockey players.
AB  - OBJECTIVE: To determine the economic burden of salary costs lost due to injury in
      the National Hockey League (NHL). METHODS: All NHL players who engaged in at
      least one regular season game during the 2009-2010 to 2011-2012 seasons comprised
      the study population. We performed a retrospective cross-sectional analysis of
      publically available media sources to collect injury and salary data. Outcome
      measurements were games missed during regular season play due to hockey-related
      injury and lost salary. RESULTS: A total of 50.9% of all NHL players missed at
      least one game within a season of play, and injuries represented a total salary
      cost of approximately US$218 million per year. Concussions alone amounted to a
      salary loss of US$42.8 million a year. Head/neck injuries and leg/foot injuries
      were the most expensive in terms of overall cost, while head/neck and shoulder
      injuries had the highest mean cost. CONCLUSIONS: NHL players commonly miss time
      due to injury, which creates a substantial burden in lost salary costs.

PMID- 24446079
TI  - Case report of sarcoma of the sella caused by postoperative radiotherapy for a
      prolactin-producing pituitary adenoma.
AB  - We report a case of sarcomatous transformation of a prolactin (PRL)-producing
      pituitary adenoma in a 27-year-old man. He originally presented with bitemporal
      visual disturbance, headache, and hyperprolactinemia 8 years earlier. Tumor
      shrinkage was confirmed by magnetic resonance imaging (MRI) during treatment with
      dopamine-receptor agonist. However, 3 years later transsphenoidal surgery had to
      be performed because of tumor re-growth. Histopathological examination revealed a
      PRL-producing adenoma with fibrotic changes. One year later, he presented with
      right-sided visual disturbance, and tumor re-growth was confirmed using MRI. He
      underwent transcranial surgery, followed by radiation therapy (50 Gy in 25
      fractions). The histological and immunostaining features were similar in both
      specimens obtained from the two operations. Four years later, he presented with
      left-sided visual disturbance, and tumor re-growth was confirmed using MRI. The
      mass lesion dramatically increased in size within 2 months, and partial removal
      of the tumor by craniotomy was performed. The specimen was histologically
      diagnosed as malignant fibrous histiocytoma (MFH). Regardless of aggressive
      chemotherapy, his clinical symptoms and imaging findings worsened rapidly. He
      died 7 months after the diagnosis of MFH. Because patients with pituitary tumor
      undergoing radiotherapy face the possibility of developing such neoplasm, long
      term follow-up is required.

PMID- 24446080
TI  - Residents'corner December 2013. sQUIZ your knowledge!

PMID- 24446082
TI  - Intra-arterial intervention chemotherapy for sarcoma and cancerous ulcer via an
      implanted pump.
AB  - To observe the efficacy of intra-arterial chemotherapy with subcutaneously
      implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31
      patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities
      who received treatment during the period from July 2003 to November 2011 at our
      hospital were recruited, including 15 male and 16 female patients, aging between
      14 and 83 with average age of 49 years old. 10 patients had tumor in upper
      extremities and 21 patients in lower extremities. The pathological types of
      studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with
      synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with
      liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases
      with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of
      cancerous ulcer were pain, infection and hemorrhage; All the studied patients
      were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy
      pump, and the patients with squamous cell carcinoma were additionally applied
      with bleomycin and patients with malignant melanoma were additionally applied
      with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of
      intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and
      total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing
      spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers.
      19 patients underwent surgery after chemotherapy, in which 16 cases had limb
      salvage surgery and 3 cases underwent lower leg amputation after chemotherapy,
      and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous
      intra-arterial targeting chemotherapy could be applied to treat refractory
      sarcoma and cancerous ulcer in extremities to significantly increase the
      chemotherapeutic concentration at tumor area so as to effectively constrain the
      tumor rupture induced main symptoms including pain, infection and bleeding, which
      would help to make a decreased blood supplied and well defined tumor boundary to
      finally decrease the recurrence rate.

PMID- 24446083
TI  - Tumor prevention in HPV8 transgenic mice by HPV8-E6 DNA vaccination.
AB  - The genus beta human papillomavirus 8 (HPV8) is involved in the development of
      cutaneous squamous cell carcinomas (SCCs) in individuals with epidermodysplasia
      verruciformis. Immunosuppressed transplant recipients are prone to harbor
      particularly high betapapillomavirus DNA loads, which may contribute to their
      highly increased risk of SCC. Tumor induction in HPV8 transgenic mice correlates
      with increased expression of viral oncogenes E6 and E2. In an attempt to prevent
      skin tumor development, we evaluated an HPV8-E6-DNA vaccine, which was able to
      stimulate a detectable HPV8-E6-specific cell-mediated immune response in 8/15
      immunized mice. When skin of HPV8 transgenic mice was grafted onto non-transgenic
      littermates, the grafted HPV8 transgenic tissue was not rejected and papillomas
      started to grow within 14 days all over the transplant of 9/9 non-vaccinated and
      7/15 not successfully vaccinated mice. In contrast, no papillomas developed in
      6/8 successfully vaccinated mice. In the other two of these eight mice, a large
      ulcerative lesion developed within the initial papilloma growth or papilloma
      development was highly delayed. As the vaccine completely or partially prevented
      papilloma development without rejecting the transplanted HPV8 positive skin, the
      immune system appears to attack only keratinocytes with increased levels of E6
      protein, which would give rise to papillomas.

PMID- 24446084
TI  - Preoperative serum hyaluronic acid level as a prognostic factor in patients
      undergoing hepatic resection for hepatocellular carcinoma.
AB  - BACKGROUND: Hyaluronic acid (HA) probably plays a critical role in tumorigenesis.
      The clinical significance of serum HA concentration in patients with
      hepatocellular carcinoma (HCC) remains to be elucidated. This study analysed the
      relationship between preoperative serum HA levels and prognosis after hepatic
      resection in patients with HCC. METHODS: Consecutive patients who underwent
      hepatic resection for HCC between September 1999 and March 2012 were included in
      this retrospective study. Serum HA levels were measured within 4 weeks before
      surgery by an immunoturbidimetric automated latex assay. The cut-off level for
      preoperative serum HA was validated using a time-dependent receiver operating
      characteristic (ROC) curve analysis. The prognostic impact of preoperative serum
      HA levels was analysed using Cox proportional hazards models. RESULTS: A total of
      506 patients of median age 66 years (405 men, 80.0 per cent) were analysed. The
      median length of follow-up was 32 months. High serum HA levels (100 ng/ml or
      above) were associated with shorter recurrence-free survival (P < 0.001) (hazard
      ratio (HR) 1.50, 95 per cent confidence interval 1.17 to 1.93; P = 0.002) and
      overall survival (P = 0.001) (HR 1.46, 1.03 to 2.07; P = 0.033). In patients with
      HCC without severe liver fibrosis, serum HA level was correlated with multiple
      tumours (P = 0.039), early recurrence (P = 0.033), and poor recurrence-free (P <
      0.001) and overall (P = 0.024) survival. CONCLUSION: High preoperative serum HA
      levels predict poor prognosis in patients with HCC after hepatic resection, and
      may serve as a future biomarker.

PMID- 24446086
TI  - Mercury and pregnancy.

PMID- 24446085
TI  - Epigenetic programing of depression during gestation.
AB  - Gestational factors play a role in the development of several neuropsychiatric
      disorders including schizophrenia and autism. In utero conditions influence
      future mental health through epigenetic mechanisms, which alter gene expression
      without affecting DNA coding sequence. Environmental factors account for at least
      60% of the risk for developing major depression, and earlier onset of depressive
      illness has been observed over the past decades. I speculate that gestational
      factors may play a greater role in programing depression than previously
      recognized. Here, I examine recent evidence for a role for gestational factors in
      programing mood disorders, and how epigenetic mechanisms mediate this effect. 

PMID- 24446087
TI  - Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or
      without cleft palate in the Brazilian population.
AB  - BACKGROUND: Although genome-wide association studies have identified several
      susceptibility loci for nonsyndromic cleft lip with or without cleft palate
      (NSCL/P) in populations around the world, the role of most loci is unknown in the
      highly heterogeneous Brazilian population. METHODS: To determine the association
      of 7 markers that showed genome-wide significant association in Brazilians with
      NSCL/P, we conducted a structured association study conditioned upon the
      individual ancestry proportions to evaluate markers at 1p36 (rs742071), 2p21
      (rs7590268), 3p11.1 (rs7632427), 8q21.3 (rs12543318), 13q31.1 (rs8001641),
      15q22.2 (rs1873147), and 17q22 (rs227731) in 505 patients with NSCL/P and 594
      healthy controls recruited from 2 different geographical regions of Brazil. The
      polymorphisms were genotyped by TaqMan 5'-exonuclease allelic discrimination
      assay, and each sample was independently typed for 40 biallelic short
      insertion/deletion markers to characterize the genomic ancestry. RESULTS: After
      Bonferroni correction for multiple tests, significant associations with NSCL/P
      were observed for rs742071, rs1873147, and rs227731. However, the frequency of
      the risk alleles varied between the geographical regions, according to the
      proportions of European and African genomic ancestry. The group enriched by
      European ancestry showed significant association with rs227731 (p = 0.001),
      whereas the group with high African ancestry was significantly associated with
      rs1873147 polymorphism (p = 0.005). The significant association with rs742071 was
      only detected in the combined sample (p = 0.005). CONCLUSION: The findings of the
      present study revealed the associations of 1p36 (rs742071), 15q22 (rs1873147),
      and 17p22 (rs227731) with NSCL/P in the Brazilian population, and further
      confirmed that the genetic heterogeneity of NSCL/P may be related to the
      different ethnic background of the affected individuals.

PMID- 24446090
TI  - The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase
      domain, is fused to KAT6A in therapy-related acute myeloid leukemia with
      t(8;19)(p11;q13).
AB  - The monocytic leukemia zinc finger protein KAT6A (formerly MOZ) gene is
      recurrently rearranged by chromosomal translocations in acute myeloid leukemia
      (AML). KAT6A is known to be fused to several genes, all of which have histone
      acetyltransferase (HAT) activity and interact with a number of transcription
      factors as a transcriptional coactivator. The present study shows that the
      leucine twenty homeobox (LEUTX) gene on 19q13 is fused to the KAT6A gene on 8p11
      in a therapy-related AML with t(8;19)(p11;q13) using the cDNA bubble PCR method.
      The fusion transcripts contained 83 nucleotides upstream of the first ATG of
      LEUTX and are presumed to create in-frame fusion proteins. LEUTX is known to have
      a homeobox domain. Expression of the LEUTX gene was only detected in placenta RNA
      by RT-PCR, but not in any tissues by Northern blot analysis. The putative LEUTX
      protein does not contain any HAT domain, and this is the first study to report
      that KAT6A can fuse to the homeobox gene. The current study, with identification
      of a new partner gene to KAT6A in a therapy-related AML, does not elucidate the
      mechanisms of leukemogenesis in KAT6A-related AML but describes a new gene with a
      different putative function.

PMID- 24446091
TI  - Factors impacting the use of antenatal care and hospital child delivery services:
      a case study of rural residents in the Enshi Autonomous Prefecture, Hubei
      Province, China.
AB  - This study was undertaken to understand the factors that impact whether rural
      women obtain antenatal care (ANC) and choose to use hospital delivery services in
      central and western China. We chose to conduct field research with the rural
      residents in Hubei Province through a combination of random sampling and
      purposive sampling methods. A mixed method approach was taken to analyze the
      factors impacting the use of ANC and hospital delivery services from the
      perspective of the villagers. Our results indicate that the quality of the
      available ANC services is poor. In particular, women who have special
      circumstances and unplanned pregnancies or who become pregnant prior to marriage
      are confronted with inadequate ANC and hospital child delivery services. The
      factors that impact whether women use or not use ANC and hospital delivery
      services and that cause women to choose hospital or home delivery can be
      understood at three levels: macro, middle, and micro. We strongly suggest that
      the policies and projects that promote maternal healthcare in rural areas be
      sustained with an added focus on including women with special circumstances.
      Village doctors can be enlisted to regularly visit pregnant women at home and to
      provide extra explanation about the ANC services available and the purpose of
      maternal healthcare. These findings and suggestions can be used by local health
      providers and decision-makers to improve the quality of ANC and hospital delivery
      services.

PMID- 24446093
TI  - Changing climate and the altitudinal range of avian malaria in the Hawaiian
      Islands - an ongoing conservation crisis on the island of Kaua'i.
AB  - Transmission of avian malaria in the Hawaiian Islands varies across altitudinal
      gradients and is greatest at elevations below 1500 m where both temperature and
      moisture are favorable for the sole mosquito vector, Culex quinquefasciatus, and
      extrinsic sporogonic development of the parasite, Plasmodium relictum. Potential
      consequences of global warming on this system have been recognized for over a
      decade with concerns that increases in mean temperatures could lead to expansion
      of malaria into habitats where cool temperatures currently limit transmission to
      highly susceptible endemic forest birds. Recent declines in two endangered
      species on the island of Kaua'i, the 'Akikiki (Oreomystis bairdi) and 'Akeke'e
      (Loxops caeruleirostris), and retreat of more common native honeycreepers to the
      last remaining high elevation habitat on the Alaka'i Plateau suggest that
      predicted changes in disease transmission may be occurring. We compared
      prevalence of malarial infections in forest birds that were sampled at three
      locations on the Plateau during 1994-1997 and again during 2007-2013, and also
      evaluated changes in the occurrence of mosquito larvae in available aquatic
      habitats during the same time periods. Prevalence of infection increased
      significantly at the lower (1100 m, 10.3% to 28.2%), middle (1250 m, 8.4% to
      12.2%), and upper ends of the Plateau (1350 m, 2.0% to 19.3%). A concurrent
      increase in detections of Culex larvae in aquatic habitats associated with stream
      margins indicates that populations of the vector are also increasing. These
      increases are at least in part due to local transmission because overall
      prevalence in Kaua'i 'Elepaio (Chasiempis sclateri), a sedentary native species,
      has increased from 17.2% to 27.0%. Increasing mean air temperatures, declining
      precipitation, and changes in streamflow that have taken place over the past 20
      years are creating environmental conditions throughout major portions of the
      Alaka'i Plateau that support increased transmission of avian malaria.

PMID- 24446094
TI  - Fitz-Hugh-Curtis syndrome in a man.

PMID- 24446095
TI  - Peroral endoscopic myotomy (POEM) for achalasia after Roux-en-Y gastric bypass.

PMID- 24446096
TI  - In vivo appearances of gallbladder carcinoma under magnifying endoscopy and probe
      based confocal laser endomicroscopy after endosonographic gallbladder drainage.

PMID- 24446097
TI  - Hemoperitoneum after endoscopic mucosal resection for Barrett's esophagus.

PMID- 24446098
TI  - Treatment of complete esophageal stenosis using endoscopic ultrasound-guided
      puncture: a novel technique for access to the distal lumen.

PMID- 24446099
TI  - Palliation of a malignant gastrocolic fistula with the use of an atrial septal
      defect occlusion device.

PMID- 24446100
TI  - Endoscopic ultrasound diagnosis of a small splenic vein aneurysm.

PMID- 24446101
TI  - Sessile serrated lesion misdiagnosed as a hyperplastic polyp.

PMID- 24446102
TI  - Extensive intramural hematoma of the esophagus following endoscopic mucosal
      resection.

PMID- 24446103
TI  - Forest cover reduces thermally suitable habitats and affects responses to a
      warmer climate predicted in a high-elevation lizard.
AB  - Warmer climates have affected animal distribution ranges, but how they may
      interact with vegetation patterns to affect habitat use, an important
      consideration for future wildlife management, has received little attention.
      Here, we use a biophysical model to investigate the potential thermal impact of
      vegetation pattern on the habitat quality of a high-elevation grassland lizard,
      Takydromus hsuehshanensis, and to predict the thermal suitability of vegetation
      for this species in a future warmer climate (assuming 3  degrees C air
      temperature increase). We assess the thermal quality of vegetation types in our
      study area (Taroko National Park in areas >1,800 m) using three ecologically
      relevant estimates of reptiles: body temperature (T b), maximum active time, and
      maximum digestive time. The results show that increasing forest canopy gradually
      cools the microclimates, hence decreasing these estimates. In the current
      landscape, sunny mountain-top grasslands are predicted to serve as high quality
      thermal habitat, whereas the dense forests that are dominant as a result of
      forest protection are too cold to provide suitable habitat. In simulated warmer
      climates, the thermal quality of dense forests increases slightly but remains
      inferior to that of grasslands. We note that the impact of warmer climates on
      this reptile will be greatly affected by future vegetation patterns, and we
      suggest that the current trend of upslope forest movement found in many other
      mountain systems could cause disadvantages to some heliothermic lizard species.

PMID- 24446104
TI  - Residents'corner December 2013. DeRmpath & Clinic: Dermatoscopic
      dermatopathologic correlation in melanoma.

PMID- 24446105
TI  - 3-D structure, volume, and DNA content of erythrocyte nuclei of polyploid fish.
AB  - We have explored the potential relationship between ploidy level, DNA content (pg
      DNA nucleus(-1)), and dimensional characteristics, such as volume (MUm(3)),
      surface area (MUm(2)), and 3-D structure of erythrocyte nuclei in a series of
      fish ploidy level models using Feulgen image analysis densitometry, flow
      cytometry, and confocal laser scanning microscopy. The species were diploid tench
      (Tinca tinca) (2n), Cuban gar (Atractosteus tristoechus) (2n), triploid tench
      (3n), evolutionary tetraploid sterlet (Acipenser ruthenus) (4n), evolutionary
      octaploid Siberian sturgeon (A. baerii) (8n), triploid Siberian sturgeon
      exhibiting dodecaploidy (12n), evolutionary 12n shortnose sturgeon (A.
      brevirostrum), and experimentally obtained sturgeon hybrids that were tetraploid,
      hexaploid (6n), heptaploid (7n), octaploid, decaploid (10n), dodecaploid and/or
      tetradecaploid (14n). Increase in ploidy was accompanied by growth of the nucleus
      and an increase in the number of flattened ellipsoid nuclei with increased
      transverse diameter. The volume (Vvoxel ) of erythrocyte nuclei, as the sum of
      voxels calculated from live cells, seems more accurate than volume (Vaxis )
      calculated from measuring the major and minor axis, especially at higher and odd
      ploidy levels. Data of absolute and relative DNA content were in agreement with
      previously published reports. Species of the same ploidy level, but differing in
      DNA content, had a similar mean erythrocyte nuclear volume (Vvoxel ), as
      demonstrated in sterlet and a hybrid of sterlet and beluga (48.3 and 48.9 MUm(3),
      respectively), with a respective mean DNA content of 3.74 and 3.10 pg DNA
      nucleus(-1). A similar relationship was found for the ploidy 6n, 10n, 12n. The
      surface-to-volume ratio decreased non-linearly with increasing ploidy. The DNA in
      erythrocyte nuclei appeared to be more densely packed with increase in ploidy
      level.

PMID- 24446106
TI  - Police commissioners call for rethink on minimum pricing of alcohol.

PMID- 24446107
TI  - Prevalence of venous thromboembolism at diagnosis of upper gastrointestinal
      cancer.
AB  - BACKGROUND: Venous thromboembolism (VTE) in patients with upper gastrointestinal
      (GI) cancer increases morbidity and mortality. This study aimed to determine the
      prevalence of VTE at diagnosis of upper GI cancer. METHODS: Patients admitted
      between February 2008 and February 2011 with upper GI cancer (pancreatic,
      extrahepatic biliary, lower oesophageal, gastro-oesophageal junction or gastric
      cancer) were investigated in a cross-sectional cohort study. At cancer diagnosis,
      all patients were examined for deep vein thrombosis (DVT) by means of bilateral
      compression ultrasonography. From February 2009 and onwards, computed tomographic
      pulmonary angiography (CTPA) was also performed for the diagnosis of pulmonary
      embolism (PE). RESULTS: Some 250 patients had ultrasonography; CTPA was performed
      in 143 patients on admission. DVT was detected in 13 (5.2 per cent) of the 250
      patients, eight (3.2 per cent) of whom were asymptomatic. DVT was correlated with
      tumour location in the pancreaticobiliary tract (odds ratio (OR) 6.27, 95 per
      cent confidence interval 1.18 to 33.38; P = 0.031) and tumour stage IV (OR 19.34,
      2.33 to 160.70; P = 0.006). PE was detected in 11 (7.7 per cent) of 143 patients,
      eight (5.6 per cent) of whom were asymptomatic. PE embolism was also
      significantly more common in patients with pancreaticobiliary tract cancer (OR
      7.81, 1.28 to 47.62; P = 0.026) and in those with stage IV disease (OR 17.19,
      1.83 to 161.50; P = 0.013). CONCLUSION: The prevalence of VTE at cancer diagnosis
      was significantly higher in patients with pancreaticobiliary tract cancer than in
      those with other forms of upper GI cancer, and in patients with advanced cancer
      stage.

PMID- 24446108
TI  - Temporal and visual source memory deficits among ecstasy/polydrug users.
AB  - OBJECTIVES: We wished to investigate whether source memory judgements are
      adversely affected by recreational illicit drug use. METHOD: Sixty-two
      ecstasy/polydrug users and 75 non ecstasy users completed a source memory task,
      in which they tried to determine whether or not a word had been previously
      presented and if so, attempted to recall the format, location and temporal
      position in which the word had occurred. RESULTS: While not differing in terms of
      the number of hits and false positive responses, ecstasy/polydrug users adopted a
      more liberal decision criterion when judging if a word had been presented
      previously. With regard to source memory, users were less able to determine the
      format in which words had been presented (upper versus lower case). Female users
      did worse than female nonusers in determining which list (first or second) a word
      was from. Unexpectedly, the current frequency of cocaine use was negative
      associated with list and case source memory performance. CONCLUSIONS: Given the
      role that source memory plays in everyday cognition, those who use cocaine more
      frequently might have more difficulty in everyday tasks such as recalling the
      sources of crucial information or making use of contextual information as an aid
      to learning.

PMID- 24446110
TI  - Metabolite profiling of enzymatically hydrolyzed and fermented forms of Opuntia
      ficus-indica and their effect on UVB-induced skin photoaging.
AB  - Fermentation of natural products is emerging as an important processing method
      and is attracting a lot of attention because it may have the advantage of having
      a new biological function. In this study, fruits of Opuntia ficus-indica were
      enzymatically hydrolyzed and then fermented with two species of yeast. We
      identified novel prominent markers in enzymatically hydrolyzed O. ficus-indica
      (EO) and fermented O. ficus-indica (FO) samples by using an ultra-performance
      liquid chromatography/quadrupole time-of-flight mass spectrometry. We also
      evaluated the effect of EO and FO on photoaging of skin cells exposed to
      ultraviolet radiation. We identified the major fermented metabolite in the FO as
      ferulic acid. Our in vitro study indicated that FO significantly enhanced the
      concentration of pro-collagen type 1 than the EO, by increasing the TGF-beta1
      production. 

PMID- 24446112
TI  - Identification and quantification of the doping agent GHRP-2 in seized unlabelled
      vials by NMR and MS: a case-report.

PMID- 24446111
TI  - ALK inhibitors of bis-ortho-alkoxy-para-piperazinesubstituted-pyrimidines and 
      triazines for cancer treatment.
AB  - Syntheses of various bis-ortho-alkoxy-para-piperazineanilino-pyrimidines and 
      triazines of KRCA-0008 analogs are described and their structure-activity
      relationship to anaplastic lymphoma kinase (ALK) is discussed. 5-trifluoromethyl
      2,4-pyrimidine analog (2) seems to be most potent in both biochemical and
      cellular assay in this study, however it shows inferior mice xenograft activity
      to Crizotinib presumably due to its sub-optimal PK parameters. 4,6-disubstituted
      pyrimidine and 2,4-disubstituted triazine derivatives of KRCA-0008 are less
      potent or inactive to ALK wt., and this observation is explained with their
      molecular modeling compared to KRCA-0008. 

PMID- 24446113
TI  - Tissue engineering scaffold for sequential release of vancomycin and rhBMP2 to
      treat bone infections.
AB  - The ability of silica calcium phosphate nanocomposite (SCPC75) for the controlled
      sequential delivery of vancomycin (Vanc) and rhBMP2 was evaluated. Fourier
      transform infrared spectroscopy analyses of the SCPC75 showed an increase in the
      bond energy of the PO4 (-3) due to the interactions with negatively charged
      moieties of Vanc. Furthermore, a decrease in the bond energy of the Si-O-Si
      functional groups was observed after rhBMP2 adsorption. In conjunction with the
      differences in bond site and bond energy at the ceramic/drug interface,
      significant differences in drug release kinetics and bioceramic dissolution rate
      were found. UV-vis spectrometry showed a burst release of Vanc in the first 8 h
      followed by a sustained release stage for up to 28 days. ELISA showed first-order
      release kinetics of rhBMP2 without burst release. The rhBMP2 release from SCPC75
      was associated with a significantly lower rate of Ca and a higher rate of Si
      dissolutions when compared with Vanc release over identical time periods.
      Differences in the release kinetic profiles of Vanc and rhBMP2 from the SCPC75
      Vanc/SCPC75-rhBMP2 scaffolds at 70/30, 50/50, or 20/80 ratios allowed for
      sequential drug release profiles that could be exploited to customize doses and
      release duration of each drug. The released rhBMP2 significantly upregulated
      MC3T3-E1 expression of collagen type I, osteopontin, and osteocalcin mRNA by 12.6
      , 3.3-, and 2.4-fold, respectively. The released Vanc demonstrated bactericidal
      effects on Staphylococcus aureus in vitro. These results suggest the potential of
      SCPC75-Vanc-rhBMP2 scaffolds in the treatment of damaged and/or infected bone.

PMID- 24446114
TI  - ["Die Fortschritte Neurologie - Psychiatrie" in 2013].

PMID- 24446115
TI  - [Neurobiology of attention deficit hyperactivity disorder].
AB  - The origin of ADHD is multifactorial and both the aetiology and pathophysiology
      of ADHD are as yet incompletely understood. The monoamine deficit hypothesis of
      ADHD postulates a dysbalance in the interaction of the neurotransmitters
      dopamine, noradrenaline and serotonin. Pathophysiological mechanisms involved in
      ADHD include alterations in fronto-striatal circuits. The currently proposed
      animal models of ADHD are heterogeneous with regard to their pathophysiological
      alterations and their ability to mimic behavioural symptoms and to predict
      response to medication. Some evidence points to a genetic basis for ADHD which is
      likely to involve many genes of small individual effects. In summary, specific
      neurobiological substrates of ADHD are unknown and multiple genetic and
      environmental factors appear to act together to create a spectrum of
      neurobiological liability. 

PMID- 24446116
TI  - [The new reimbursement for psychiatry and psychosomatics - challenges,
      opportunities and risks of the new financing system].
AB  - With the implementation of S 17 d KHG which provides for the introduction of a
      new, much more performance-based and transparent reimbursement system for
      psychiatric and psychosomatic hospitals, the Federal Ministry of Health sends the
      psychiatric and psychosomatic facilities in Germany into a previously unexplored
      area. Since 2013, there is the possibility of voluntary participation in the new
      system. Valid from 2015, every other institution will have to deal with the new
      challenges, opportunities and risks coming along with the structural changes,
      even though this fact will not have any impact on the individual hospital revenue
      budget until the end of 2016. There is still some time left to get used to the
      new system. This paper summarises the key data on the new reimbursement system
      and explains its content as well as how it works. In addition to that this paper
      goes into the classification system and clarifies what is essential for a solid
      preparation. Finally, it comments on the most common criticisms emerging since
      2009. How the new system will develop remains to be seen. The fact that it will
      evolve seems to be certain in terms of a "learning system". It is up to all
      parties to promote the learning process so as to make effective use of existing
      potential and keep risks to a minimum. 

PMID- 24446117
TI  - [Botulinum toxin injections for chronic migraine in adolescents - an early
      therapeutic option in the transition from neuropaediatrics to neurology].
AB  - BACKGROUND: The prevalence of chronic headaches in children and adolescents is up
      to 2 % resulting in the beginning of the later typical headache careers of
      adults. The therapy for chronic migraine with botulinum toxin is now established
      in adults. However, there is only limited experience in the use of botulinum
      toxin in paediatric patients. METHODS: 10 patients aged 13 - 17 years who
      suffered from chronic migraine according to the IHS criteria were injected at 31
      specific injection points of the head and neck muscles with a total amount of 150
      IE of botulinum toxin A (Botox(r)) according to the approved scheme. The number
      of headache days per month over the following 9 months was recorded and side
      effects were retrospectively determined. RESULTS: The responder rate (that is
      reduction of headache days per month more than 50 %) was 7/10 at three months
      after the injection. On average the number of headache days per month was reduced
      from 19.2 days to a minimum of 10.1 days. After three to six months the number of
      headache days increased again in all responders. Slight local side effects such
      as redness or temporary pain were observed in all patients, but severe side
      effects such as infections, fever, ptosis or allergic reactions did not occur.
      DISCUSSION: This small case series shows that the therapy for chronic migraine
      with botulinum toxin A can also be effective and safe in adolescents. As many
      adolescents still suffer from headaches later as adults a link between
      neuropaediatricians and neurologists is justifiable. An early botulinum toxin
      therapy followed by the transition of the adolescents would be helpful.

PMID- 24446118
TI  - [Work rehabilitation for people with severe mental illness].

PMID- 24446119
TI  - [78% of stroke patients treated on 534 stroke units - (still?) fiction!].

PMID- 24446120
TI  - [Position statement: Thrombolysis for acute stroke--regional healthcare in
      Germany].

PMID- 24446121
TI  - Residents'corner December 2013. PhotogRaphic Clues: Choosing the best camera for
      dermatologic photography.

PMID- 24446122
TI  - Recurrent mutation of JAK3 in T-cell prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL) is an aggressive post-thymic T-cell
      malignancy characterized by the recurrent inv(14)(q11q32)/t(14;14)(q11;q32) or
      t(X;14)(q28;q11) leading to activation of either the TCL1 or MTCP1 gene,
      respectively. However, these primary genetic events are insufficient to drive
      leukemogenesis. Recently, activating mutations in JAK3 have been identified in
      other T-cell malignancies. Since JAK3 is essential for T-cell maturation, we
      analyzed a cohort of 32 T-PLL patients for mutational hot spots in the JAK3 gene
      using a step-wise screening approach. We identified 14 mutations in 11 of 32
      patients (34%). The most frequently detected mutation in our cohort was M511I
      (seen in 57% of cases) previously described as an activating change in other T
      cell malignancies. Three patients carried two mutations in JAK3. In two patients
      M511I and R657Q were simultaneously detected and in another patient V674F and
      V678L. In the latter case we could demonstrate that the mutations were on the
      same allele in cis. Protein modeling and homology analyses of mutations present
      in other members of the JAK family suggested that these mutations likely activate
      JAK3, possibly by disrupting the activation loop and the interface between N and
      C lobes, increasing the accessibility of the catalytic loop. In addition, four of
      the 21 patients lacking a JAK3 point mutation presented an aberrant karyotype
      involving the chromosomal band 19p13 harboring the JAK3 locus. The finding of
      recurrent activating JAK3 mutations in patients with T-PLL could enable the use
      of JAK3 inhibitors to treat patients with this unfavorable malignancy who
      otherwise have a very poor prognosis.

PMID- 24446123
TI  - Somatic cells with a heavy mitochondrial DNA mutational load render induced
      pluripotent stem cells with distinct differentiation defects.
AB  - It has become increasingly clear that several age-associated pathologies
      associate with mutations in the mitochondrial genome. Experimental modeling of
      such events has revealed that acquisition of mitochondrial DNA (mtDNA) damage can
      impair respiratory function and, as a consequence, can lead to widespread decline
      in cellular function. This includes premature aging syndromes. By taking
      advantage of a mutator mouse model with an error-prone mtDNA polymerase, we here
      investigated the impact of an established mtDNA mutational load with regards to
      the generation, maintenance, and differentiation of induced pluripotent stem
      (iPS) cells. We demonstrate that somatic cells with a heavy mtDNA mutation burden
      were amenable for reprogramming into iPS cells. However, mutator iPS cells
      displayed delayed proliferation kinetics and harbored extensive differentiation
      defects. While mutator iPS cells had normal ATP levels and glycolytic activity,
      the induction of differentiation coincided with drastic decreases in ATP
      production and a hyperactive glycolysis. These data demonstrate the differential
      requirements of mitochondrial integrity for pluripotent stem cell self-renewal
      versus differentiation and highlight the relevance of assessing the mitochondrial
      genome when aiming to generate iPS cells with robust differentiation potential.

PMID- 24446126
TI  - Comment on "synthesis, characterization, and structures of persistent aniline
      radical cation": it is a protonated aniline and not an aniline radical cation.
AB  - The same, but different: The reaction of tri-tert-butylaniline (TBA) with AgSbF6
      in CH2 Cl2 produces a green-colored intermediate which undergoes decomposition to
      form a protonated aniline (TBAH(+) SbF6 (-) ). Crystals of the protonated aniline
      salt were analyzed by X-ray diffraction and found to have the same crystal
      characteristics as the crystals of the supposed cation radical first identified
      in 2012. 

PMID- 24446127
TI  - Systematic review of tibial nerve stimulation to treat faecal incontinence.
AB  - BACKGROUND: Two forms of tibial nerve stimulation are used to treat faecal
      incontinence (FI): percutaneous (PTNS) and transcutaneous (TTNS) tibial nerve
      stimulation. This article critically appraises the literature on both procedures.
      METHODS: A systematic review was performed adhering to the PRISMA framework. A
      comprehensive literature search was conducted, with systematic methodological
      quality assessment and data extraction. Summary measures for individual outcome
      variables are reported. RESULTS: Twelve articles met eligibility criteria; six
      related to PTNS, five to TTNS, and one to both procedures. These included ten
      case series and two randomized clinical trials (RCTs). Case series were evaluated
      using the National Institute for Health and Care Excellence quality assessment
      for case series, scoring 3-6 of 8. RCTs were evaluated using the Jadad score,
      scoring 4 of a possible 5 marks, and the Cochrane Collaboration bias assessment
      tool. From one RCT and case series reports, the success rate of PTNS, based on
      the proportion of patients who achieved a reduction in weekly FI episodes of at
      least 50 per cent, was 63-82 per cent, and that of TTNS was 0-45 per cent. In an
      RCT of TTNS versus sham, no patient had a reduction in weekly FI episodes of 50
      per cent or more, whereas in an RCT of PTNS versus TTNS versus sham, 82 per cent
      of patients undergoing PTNS, 45 per cent of those having TTNS, and 13 per cent of
      patients in the sham group had treatment success. CONCLUSION: PTNS and TTNS
      result in significant improvements in some outcome measures; however, TTNS was
      not superior to sham stimulation in a large, adequately powered, RCT. As no
      adequate RCT of PTNS versus sham has been conducted, conclusions cannot be drawn
      regarding this treatment.

PMID- 24446129
TI  - A mass spectrometric approach for probing the stability of bioorganic radicals.
AB  - Glycyl radicals are important bioorganic radical species involved in enzymatic
      catalysis. Herein, we demonstrate that the stability of glycyl-type radicals (X
      (.) CH-Y) can be tuned on a molecular level by varying the X and Y substituents
      and experimentally probed by mass spectrometry. This approach is based on the gas
      phase dissociation of cysteine sulfinyl radical (X-Cys SO .-Y) ions through
      homolysis of a Calpha ?Cbeta bond. This fragmentation produces a glycyl-type
      radical upon losing CH2 SO, and the degree of this loss is closely tied to the
      stability of the as-formed radical. Theoretical calculations indicate that the
      energy of the Calpha ?Cbeta bond homolysis is predominantly affected by the
      stability of the glycyl radical product through the captodative effect, rather
      than that of the parent sulfinyl radical. This finding suggests a novel
      experimental method to probe the stability of bioorganic radicals, which can
      potentially broaden our understanding of these important reactive intermediates. 

PMID- 24446128
TI  - Upregulation of androgen-responsive genes and transforming growth factor-beta1
      cascade genes in a rat model of non-bacterial prostatic inflammation.
AB  - BACKGROUND: Prostatic inflammation is associated with the development of
      prostatic hyperplasia. We investigated the effects of prostatic inflammation on
      expression levels of androgen-responsive genes and growth factors in the
      prostate. METHODS: Prostatic inflammation was induced by formalin injection into
      bilateral ventral lobes of the prostate of male SD rats. After 28 days, the
      prostate was harvested for analyses of proinflammatory cytokines, androgen
      responsive genes in the epithelium, and TGF-beta1 cascade genes in the stroma.
      Some rats were given a COX-2 inhibitor (celecoxib; 10 mg/kg/day) by oral gavage
      for 28 days. RESULTS: The formalin-injected prostate exhibited widespread low
      grade inflammation (<50 leukocytes/10,000 MUm(2) ) along with focal high-grade
      inflammation (>100 leukocytes/10,000 MUm(2) ) in limited areas. Compared to
      control, formalin-injected prostate exhibited a 2.5-fold to sixfold increased
      protein expression of IL-1alpha, IL-1beta, and IL-6. In the low-grade
      inflammatory regions, threefold to ninefold and twofold to threefold
      upregulations of mRNA levels of androgen receptors/androgen-responsive genes and
      TGF-beta1 cascade genes were respectively, observed in the epithelium and stroma
      obtained by laser-capture microdissection. Positive staining for androgen
      receptors in the epithelial nuclei, and TGF-beta1, IL-6, and COX-2 in the stroma
      was increased in the low-grade inflammation area. COX-2 inhibitor treatment
      suppressed these upregulations of cytokines, androgen-responsive, and TGF-beta1
      cascade genes. CONCLUSIONS: Prostatic inflammation induced increased expression
      of androgen-responsive genes in the epithelium and TGF-beta1 cascade genes in the
      stroma, which were suppressed by COX-2 inhibitors, suggesting that activation of
      these genes in the low-grade inflammatory region might be involved in the
      development of symptomatic BPH.

PMID- 24446130
TI  - Cell cultures in uterine leiomyomas: rapid disappearance of cells carrying MED12
      mutations.
AB  - Uterine leiomyomas (UL) are the most frequent symptomatic human tumors.
      Nevertheless, their molecular pathogenesis is not yet fully understood. To learn
      more about the biology of these common neoplasms and their response to treatment,
      cell cultures derived from UL are a frequently used model system, but until
      recently appropriate genetic markers confirming their origin from the tumor cell
      population were lacking for most UL, i.e., those not displaying karyotypic
      abnormalities. The identification of MED12 mutations in the majority of UL makes
      it possible to trace the tumor cell population during in vitro passaging in the
      absence of cytogenetic abnormalities. The present study is addressing the in
      vitro survival of cells carrying MED12 mutations and its association with
      karyotypic alterations. The results challenge numerous in vitro studies into the
      biology and behavior of leiomyomas. Cells of one genetic subtype of UL, i.e.,
      those with rearrangements of the high mobility AT-hook 2 protein gene (HMGA2),
      seem to be able to proliferate in vitro for many passages whereas tumor cells
      from the much more frequent MED12-mutated lesions barely survive even the first
      passages. Apparently, for the most frequent type of human UL no good in vitro
      model seems to exist because cells do not survive culturing. On the other hand,
      this inability may point to an Achilles' heel of this type of UL.

PMID- 24446131
TI  - Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem
      cells: a model of molecular convergence for stemness.
AB  - The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells
      (HSCs) without overriding the normal stem cell pool size. A similar enhancement
      of HSC self-renewal occurs when signal transducer and activator of transcription
      3 (STAT3) is activated in HSCs. In this study, to gain insight into the
      functional organization of individual transcription factors (TFs) that have
      similar effects on HSCs, we investigated the molecular interplay between HoxB4
      and STAT3 in the regulation of HSC self-renewal. We found that while STAT3-C or
      HoxB4 similarly enhanced the in vitro self-renewal and in vivo repopulating
      activities of HSCs, simultaneous transduction of both TFs did not have additive
      effects, indicating their functional redundancy in HSCs. In addition, activation
      of STAT3 did not cause changes in the expression levels of HoxB4. In contrast,
      the inhibition of STAT3 activity in HoxB4-overexpressing hematopoietic cells
      significantly abrogated the enhancing effects of HoxB4, and the upregulation of
      HoxB4 caused a ligand-independent Tyr-phosphorylation of STAT3. Microarray
      analysis revealed a significant overlap of the transcriptomes regulated by STAT3
      and HoxB4 in undifferentiated hematopoietic cells. Moreover, a gene set
      enrichment analysis showed significant overlap in the candidate TFs that can
      recapitulate the transcriptional changes induced by HoxB4 or STAT3.
      Interestingly, among these common TFs were the pluripotency-related genes Oct-4
      and Nanog. These results indicate that tissue-specific TFs regulating HSC self
      renewal are functionally organized to play an equivalent role in transcription
      and provide insights into the functional convergence of multiple entries of TFs
      toward a conserved transcription program for the stem cell state.

PMID- 24446132
TI  - Inference concerning a common dispersion of several treatment groups in the
      analysis of over/underdispersed count data.
AB  - Over/underdispersed count data arise in many biostatistical practices in which a
      number of different treatment groups are compared in an experiment. In the
      analysis of several treatment groups of such count data, a very common
      statistical inference problem is to test whether these data come from the same
      population. The usual practice for testing homogeneity of several treatment
      groups in terms of means and dispersions is first to test the equality of
      dispersions and then to test the equality of the means based on the result of the
      test for equality of dispersions. Previous studies reported test procedures for
      testing the homogeneity of the means of several treatment groups with an
      assumption of equal or unequal dispersions. This article develops test procedures
      for testing the validity of the equal or unequal dispersions assumption of
      several treatment groups in the analysis of over/underdispersed count data. We
      consider the C(alpha) test based on the maximum likelihood (ML) method using the
      negative binomial model as well as the three other C(alpha) tests based on the
      method of moments, extended quasi-likelihood, and double extended quasi
      likelihood using the models specified by the first two moments of counts. Monte
      Carlo simulations are then used to study the comparative behavior of these
      C(alpha) tests along with the likelihood ratio test in terms of size and power.
      The simulation results demonstrate that all four statistics hold the nominal
      level reasonably well in most of the data situations studied here, and the
      C(alpha) test based on ML shows some edge in power over the other three C(alpha)
      tests. Finally, applications to biostatistical practices are analyzed. 

PMID- 24446133
TI  - Lessons learned in breast cancer surgery.

PMID- 24446134
TI  - New drug combination for execution in US leaves hospitals in short supply.

PMID- 24446135
TI  - [From national strategic plans to operational implementation: opportunities and
      risks].
AB  - Currently, all countries in Africa are - to various degrees - involved in reform
      and planning programs, either because they chose to or at the behest of
      international institutions working with them. Here we present an operational
      definition of a strategic plan and then analyze the factors that promote and
      constrain the planning process and the implementation of the plan thus developed.

PMID- 24446136
TI  - [What causes regional differences?].

PMID- 24446139
TI  - [A formula for health].

PMID- 24446140
TI  - [Development costs, regulation and audit in the German SHI Drug Sector].

PMID- 24446141
TI  - Integrated antimicrobial and nonfouling zwitterionic polymers.
AB  - Zwitterionic polymers are generally viewed as a new class of nonfouling
      materials. Unlike their poly(ethylene glycol) (PEG) counterparts, zwitterionic
      polymers have a broader chemical diversity and greater freedom for molecular
      design. In this Minireview, we highlight recent microbiological applications of
      zwitterionic polymers and their derivatives, with an emphasis on several unique
      molecular strategies to integrate antimicrobial and nonfouling properties. We
      will also discuss our insights into the bacterial nonfouling performance of
      zwitterionic polymers and one example of engineering zwitterionic polymer
      derivatives for antimicrobial wound-dressing applications. 

PMID- 24446142
TI  - Involvement of cdc42/Rho kinase in apoA-I-mediated cholesterol efflux through
      interaction between cytosolic lipid-protein particles and microtubules in rat
      astrocytes.
AB  - Activation of cdc42 reportedly enhances apoA-I-mediated cholesterol release
      through ATP-binding cassette transporter A1 (ABCA1). We examined the involvement
      of cdc42 and Rho kinase in intracellular cholesterol transport for release of
      cholesterol after the interaction between apoA-I and ABCA1 in astrocytes.
      Exogenously added apoA-I increased the GTP-bound form of cdc42 and enhanced Rho
      kinase activity in rat astrocytes. Suppression of ABCA1 expression by siRNA
      substantially repressed both cellular level of GTP-bound cdc42 and Rho kinase
      activity, indicating that these reactions require ABCA1. ApoA-I-mediated lipid
      release and Rho kinase activation were inhibited by not only Rho kinase inhibitor
      but also cdc42 siRNA. These findings suggest that cdc42 is activated by the
      interaction between apoA-I and ABCA1 and enhances cholesterol release through the
      activation of Rho kinase. ApoA-I increased the binding of Rock1, one of the Rho
      kinases, to reconstituted microtubule-like filaments (rMT). Y-27632 suppressed
      not only the association of rMT with the cytosolic lipid-protein particles (CLPP)
      related proteins and lipids but also the intracellular transport of newly
      synthesized cholesterol to the plasma membrane in rat astrocytes treated with
      apoA-I without inhibiting cholesterol synthesis. Finally, cdc42 siRNA reduced
      apoA-I-induced interaction between rMT and major players in intracellular
      cholesterol trafficking, such as caveolin-1 and Rock1, suggesting a regulatory
      role of Rho family proteins in the apoA-I-mediated intracellular cholesterol
      transport. We conclude that ABCA1/cdc42/Rho kinase signaling is involved in apoA
      I-induced intracellular cholesterol transport and apoA-I-mediated cholesterol
      release in rat astrocytes.

PMID- 24446147
TI  - Genome-wide analysis of esophageal adenocarcinoma yields specific copy number
      aberrations that correlate with prognosis.
AB  - The incidence of esophageal adenocarcinoma (EAC) has been increasing rapidly for
      the past 3 decades in Western (Caucasian) populations. Curative treatment is
      based around esophagectomy, which has a major impact on quality of life. For
      those suitable for treatment with curative intent, 5-year survival is ~30%. More
      accurate prognostic tools are therefore needed, and copy number aberrations
      (CNAs) may offer the ability to act as prospective biomarkers in this regard. We
      performed a genome-wide examination of CNAs in 54 samples of EAC using single
      nucleotide polymorphism (SNP) arrays. Our aims were to describe frequent regions
      of CNA, to define driver CNAs, and to identify CNAs that correlated with
      survival. Regions of frequent amplification included oncogenes such as EGFR, MYC,
      KLF12, and ERBB2, while frequently deleted regions included tumor suppressor
      genes such as CDKN2A/B, PTPRD, FHIT, and SMAD4. The genomic identification of
      significant targets in cancer (GISTIC) algorithm identified 24 regions of gain
      and 28 regions of loss that were likely to contain driver changes. We discovered
      61 genes in five regions that, when stratified by CNA type (gain or loss),
      correlated with a statistically significant difference in survival. Pathway
      analysis of the genes residing in both the GISTIC and prognostic regions showed
      they were significantly enriched for cancer-related networks. Finally, we
      discovered that copy-neutral loss of heterozygosity is a frequent mechanism of
      CNA in genes currently targetable by chemotherapy, potentially leading to under
      reporting of cases suitable for such treatment.

PMID- 24446148
TI  - PbS colloidal quantum-dot-sensitized inorganic-organic hybrid solar cells with
      radial-directional charge transport.

PMID- 24446149
TI  - Macrophage-inducing FasL on chondrocytes forms immune privilege in cartilage
      tissue engineering, enhancing in vivo regeneration.
AB  - To obtain stable outcomes in regenerative medicine, controlling inflammatory
      reactions is a requirement. Previously, auricular chondrocytes in tissue
      engineered cartilage have been shown to express factors related to immune
      privilege including Fas ligand (FasL) in mice. Since elucidation of mechanism on
      immune privilege formed in cartilage regeneration may contribute to suppression
      of excessive inflammation, in this study, we investigated the function of FasL
      and induction of immune privilege in tissue-engineered cartilage using a mouse
      subcutaneous model. When cocultured, auricular chondrocytes of FasL-dysfunctional
      mice, C57BL/6JSlc-gld/gld (gld), induced less cell death and apoptosis of
      macrophage-like cells, RAW264, compared with chondrocytes of C57BL/6 mice (wild),
      suggesting that FasL on chondrocytes could induce the apoptosis of macrophages.
      Meanwhile, the viability of chondrocytes was hardly affected by cocultured
      RAW264, although the expression of type II collagen was decreased, indicating
      that macrophages could hamper the maturation of chondrocytes. Tissue-engineered
      cartilage containing gld chondrocytes exhibited greater infiltration of
      macrophages, with less accumulation of proteoglycan than did wild constructs.
      Analysis of the coculture medium identified G-CSF as an inducer of FasL on
      chondrocytes, and G-CSF-treated tissue-engineered cartilage showed less
      infiltration of macrophages, with increased formation of cartilage after
      transplantation. The interactions between chondrocytes and macrophages may
      increase G-CSF secretion in macrophages and induce FasL on chondrocytes, which in
      turn induce the apoptosis of macrophages and suppress tissue reactions, promoting
      the maturation of tissue-engineered cartilage. These findings provide scientific
      insight into the mechanism of autologous chondrocyte transplantation, which could
      be applied as a novel strategy for cartilage tissue engineering.

PMID- 24446150
TI  - An empirically informed critique of Habermas' argument from human nature.
AB  - In a near-future world of bionics and biotechnology, the main ethical and
      political issue will be the definition of who we are. Could biomedical
      enhancements transform us to such an extent that we would be other than human?
      Habermas argues that any genetic enhancement intervention that could potentially
      alter 'human nature' should be morally prohibited since it alters the child's
      nature or the very essence that makes the child who he is. This practice also
      commits the child to a specific life project or, in any case, it puts specific
      restrictions on his freedom to choose a life of his own. Ultimately, genetic
      enhancement jeopardizes the very foundations of moral equality. I contend that
      Habermas' argument is based either on a series of presuppositions that imply a
      gross misunderstanding of evolution or the relevant factual information
      concerning the action we are about to morally assess is not empirically
      supported. Hence, the argument from human nature is based on a series of false or
      problematic assumptions, and, as such, it fails to play the normative role
      intended by Habermas.

PMID- 24446151
TI  - Protecting human health and security in digital Europe: how to deal with the
      "privacy paradox"?
AB  - This article is the result of an international research between law and ethics
      scholars from Universities in France and Switzerland, who have been closely
      collaborating with technical experts on the design and use of information and
      communication technologies in the fields of human health and security. The
      interdisciplinary approach is a unique feature and guarantees important new
      insights in the social, ethical and legal implications of these technologies for
      the individual and society as a whole. Its aim is to shed light on the tension
      between secrecy and transparency in the digital era. A special focus is put from
      the perspectives of psychology, medical ethics and European law on the
      contradiction between individuals' motivations for consented processing of
      personal data and their fears about unknown disclosure, transferal and sharing of
      personal data via information and communication technologies (named the "privacy
      paradox"). Potential benefits and harms for the individual and society resulting
      from the use of computers, mobile phones, the Internet and social media are being
      discussed. Furthermore, the authors point out the ethical and legal limitations
      inherent to the processing of personal data in a democratic society governed by
      the rule of law. Finally, they seek to demonstrate that the impact of information
      and communication technology use on the individuals' well-being, the latter being
      closely correlated with a high level of fundamental rights protection in Europe,
      is a promising feature of the socalled "e-democracy" as a new way to collectively
      attribute meaning to large-scale online actions, motivations and ideas.

PMID- 24446152
TI  - Cellular interactions and biological responses to titanium dioxide nanoparticles
      in HepG2 and BEAS-2B cells: role of cell culture media.
AB  - We showed previously that exposure of human lung cells (BEAS-2B) to TiO2
      nanoparticles (nano-TiO2 ) produced micronuclei (MN) only when the final
      concentration of protein in the cell-culture medium was at least 1%.
      Nanoparticles localize in the liver; thus, we exposed human liver cells (HepG2)
      to nano-TiO2 and found the same requirement for MN induction. Nano-TiO2 also
      formed small agglomerates in medium containing as little as 1% protein and caused
      cellular interaction as measured by side scatter by flow cytometry and DNA damage
      (comet assay) in HepG2 cells. Nano-TiO2 also increased the activity of the
      inflammatory factor NFkB but not of AP1 in a reporter-gene HepG2 cell line.
      Suspension of nano-TiO2 in medium containing 0.1% protein was sufficient for
      induction of MN by the nanoparticles in either BEAS-2B or HepG2 cells as long the
      final concentration of protein in the cell-culture medium was at least 1%.

PMID- 24446154
TI  - Differential impact of changes in adiposity distribution on insulin resistance
      and adiponectin variations over 4 years in normal weight young adults.
AB  - The aim of the study was to evaluate the influence of weight gain and changes in
      adiposity distribution on insulin resistance and circulating adiponectin
      variations over 4 years in free-living normal weight young adults. In this
      prospective observational cohort (n=42 women, 18 men), anthropometric
      measurements and blood samples were collected in the fasting state at baseline
      and at 4 years. Insulin resistance was estimated using the homeostatic model
      assessment (HOMA-IR). Circulating adiponectin levels were determined by
      radioimmunoassay. To investigate increase in adiposity more specifically,
      subsidiary analyses were performed in a subgroup of individuals (n=31) who gained
      adiposity over the course of the 4-year follow-up (defined as gain >1% in percent
      body fat). Regression analyses were performed to adjust for sex, age, parental
      education, lifestyle, and fitness levels. At baseline, the participants were
      young adults (age=20.0 years old) in the normal weight range [body mass index
      (BMI)=22.7 kg/m2 (IQR=21.1-24.4)]. Median change in body fat percentage was +1.4%
      (IQR=-0.3-3.4; p=0.01) and in waist circumference was +1.2 cm (IQR=-2.6-5.3;
      p=0.05). In the subgroup of individuals who gained more than 1% body fat,
      increase in HOMA-IR was associated with an increase in BMI (r=0.44; p=0.01;
      p<0.01 in fully adjusted model), while decrease in adiponectin levels was
      associated with an increase in waist circumference (r=-0.38; p=0.03) but this was
      no longer significant after adjustment for sex and other potential confounders
      (p=0.14). In a population of young adults, small variations in adiposity within
      the normal weight range were associated with increase in insulin resistance. 

PMID- 24446153
TI  - The Mediterranean diet adoption improves metabolic, oxidative, and inflammatory
      abnormalities in Algerian metabolic syndrome patients.
AB  - This study was aimed to explore the effects of Mediterranean diet (MD) adoption
      on insulin resistance, oxidative, and inflammatory status in metabolic syndrome
      (MS) patients. Eighty four patients with MS were randomly recruited in the
      medical centers of Oran, Algeria. Eighteen healthy participants were selected as
      a control group. Among these 84 patients, only 36 patients completed the
      nutritional advices for 3 months. Patients were instructed to follow a
      Mediterranean-style diet and received some other selected nutritional and
      physical activity instructions. Anthropometric measurements were performed and a
      questionnaire was used to assess dietary intake. Blood samples were drawn at
      baseline and after 3 months of nutritional intervention from all subjects. At
      baseline, the MS patients were obese and had altered anthropometric parameters,
      higher systolic and diastolic blood pressure, plasma lipids, glucose, insulin,
      HOMA-IR, HbA1c, urea, creatinine, uric acid, and lower albumin compared to
      healthy subjects. A decrease in plasma, erythrocyte, and platelet antioxidant
      enzymes, and a rise in lipid and protein oxidation, plasma CRP, and fibrinogen
      were noted in the MS patients. Moreover, they had an unbalanced dietary pattern
      when compared to Mediterranean recommendations. Patients following the
      Mediterranean-style diet had significantly reduced weight, BMI, waist
      circumference, waist/hip circumference ratio, decreased systolic and diastolic
      blood pressure, plasma glucose, insulin, HOMA-IR, HbA1c, cholesterol,
      triacylglycerols, CRP, urea, creatinine, creatinine clearance, lipid and protein
      oxidation, and higher plasma, erythrocyte, and platelet antioxidant enzymes. In
      conclusion, a lifestyle intervention based mainly on nutritional advices improves
      metabolic, oxidative, and inflammatory abnormalities of metabolic syndrome. 

PMID- 24446155
TI  - Color flow Doppler sonography for the etiologic diagnosis of thyrotoxicosis.
AB  - The objective of this prospective study was to compare the results of color flow
      Doppler sonography (CFDS) and radioiodine scintigraphy in patients with
      thyrotoxicosis. A total of 176 patients, 102 with clinical thyrotoxicosis and 74
      with subclinical dysfunction, were included. Pregnant and breast-feeding women,
      patients using amiodarone or recently exposed to iodinated contrast, and patients
      treated with antithyroid drugs were excluded. Total T3, free T4, TSH, and anti
      TSH receptor antibodies were measured before scintigraphy and CFDS. Excluding one
      patient whose etiology of thyrotoxicosis remained undefined, CFDS showed 100%
      specificity. In fact, in all 10 cases in which scintigraphy and CFDS provided
      discordant results, the diagnosis suggested by the latter was correct. In
      patients with clinical thyrotoxicosis, the sensitivity of CFDS was 96% for
      diffuse toxic goiter, 95% for the absence of hyperfunction, and 100% for toxic
      nodular disease. In patients with subclinical dysfunction, the sensitivity of
      CFDS was 72.7% for diffuse toxic goiter, 90% for toxic adenoma, and 86.6% for
      toxic multinodular disease. CFDS was inconclusive in patients with parenchymal
      blood flow with patchy uneven distribution or with macronodules in which nodule
      vascularity compared to the remaining parenchyma did not permit to establish the
      diagnosis with certainty. CFDS can be used instead of scintigraphy not only in
      situations in which the latter is contraindicated or of limited value to define
      the etiology of thyrotoxicosis. 

PMID- 24446156
TI  - miRNAs with the potential to distinguish follicular thyroid carcinomas from
      benign follicular thyroid tumors: results of a meta-analysis.
AB  - The detection of somatic mutations in indeterminate or follicular proliferation
      fine-needle aspiration cytologies (FNACs) is able to clarify only a subgroup of
      those FNACs. Therefore, further markers to differentiate this problematic FNAC
      category by the identification of mutation negative thyroid cancers and benign
      nodules are urgently needed. Our objective was to evaluate previously published
      miRNA markers and discover novel ones from all publicly available miRNA
      expression profiling data sets. By literature review and data repository search
      we gathered 3 data sets describing human miRNA expression profiles of follicular
      thyroid cancer (FTC) and follicular adenoma (FA) samples. Literature review
      summarized 27 previously published miRNAs, which were validated in the 3
      available data sets. By means of uniform statistical analysis 6 further miRNAs
      were identified and tested in an independent, previously published microarray
      data set. Meta-analysis confirmed 7 out of 27 previously published, and 4 out of
      6 de novo identified miRNAs. The low confirmation rate of previously published
      miRNA markers was induced by low numbers of samples in the analyzed studies and
      high false discovery rates that were higher than 0.2. Finally, miR-637, miR-181c
      3p, miR-206, and miR-7-5p were discovered as de novo potential FTC markers and
      validated in at least one independent, previously published data set. Two out of
      these new identified miRNAs (miR-7-5p and miR-206) were validated by qPCR in an
      independent sample set of 32 FTC and 46 FA samples. Especially miR-7-5p was able
      to differentiate benign and malignant thyroid tumors in several datasets. 

PMID- 24446157
TI  - Estrogen withdrawal from osteoblasts and osteocytes causes increased
      mineralization and apoptosis.
AB  - Recent studies have demonstrated increased bone mineral heterogeneity following
      estrogen withdrawal in vivo. Such changes likely contribute to fracture risk
      during post-menopausal osteoporosis since tissue mineralization is correlated
      with bone strength and stiffness. However, the cellular mechanisms responsible
      for increased mineral variability have not yet been distinguished. The objective
      of this study is to elucidate how alterations in mineral distribution are
      initiated during estrogen depletion. Specifically, we tested two separate
      hypotheses; (1) estrogen deficiency directly alters osteoblast mineralization and
      (2) estrogen deficiency increases bone cell apoptosis. Osteoblast-like cells
      (MC3T3-E1) and osteocyte-like cells (MLO-Y4) were pretreated with or without
      estrogen (17beta-estradiol) for 14 days. Estrogen deficiency was subsequently
      induced by either withdrawing estrogen from cells or blocking estrogen receptors
      using an estrogen antagonist, fulvestrant (ICI 182,780). Cell number (Hoechst
      DNA), alkaline phosphatase activity (p-NPP), mineralization (alizarin red) and
      apoptosis (Caspase 3/7) were evaluated. Whether estrogen withdrawal altered
      apoptosis rates in the presence of an apoptosis promoting agent (etoposide) was
      also determined. Interestingly, estrogen withdrawal from cells accustomed to
      estrogen exposure caused significantly increased osteoblast mineralization and
      osteocyte apoptosis compared with continued estrogen treatment. In contrast,
      blocking estrogen receptors with fulvestrant abrogated the mineralization induced
      by estrogen treatment. When apoptosis was induced using etoposide, cells
      undergoing estrogen withdrawal increased apoptosis compared to cells with
      continued estrogen treatment. Recognizing the underlying mechanisms regulating
      bone cell mineralization and apoptosis during estrogen deficiency and their
      consequences is necessary to further our knowledge of osteoporosis. 

PMID- 24446158
TI  - TSH prevents bone resorption and with calcitriol synergistically stimulates bone
      formation in rats with low levels of calciotropic hormones.
AB  - Thyroid-stimulating hormone exerts both antiresorptive and anabolic effects on
      bone remodeling in aged ovariectomized rats and thyroid stimulating hormone
      receptor null mice, supported by clinical results demonstrating that low thyroid
      stimulating hormone level is associated with increased bone loss. To further
      explore the effect of thyroid-stimulating hormone on bone metabolism we
      introduced here a rat model with removed thyroid and parathyroid glands to obtain
      low serum concentrations of thyroid and parathyroid hormone, calcitonin and
      1,25(OH)2D3. Surgery resulted in hypocalcemia, low parathyroid and thyroid
      hormone, 1,25(OH)2D3, C-telopeptide, and osteocalcin serum level. Intermittent
      administration of thyroid-stimulating hormone resulted in a further decrease of
      serum calcium and decreased level of serum C-telopeptide due to the suppression
      of bone resorption, while in the same animals osteocalcin in serum was higher
      indicating an increased bone formation rate. A combination of thyroid-stimulating
      hormone and 1,25(OH)2D3 significantly increased the serum Ca2+, C-telopeptide and
      serum osteocalcin values. MicroCT analyses of the distal femur and proximal tibia
      showed that rats treated with 1,25(OH)2D3 alone or in a combination with thyroid
      stimulating hormone had an increased trabecular bone volume, and enhanced
      trabecular bone quality. Biomechanical testing of the trabecular bone showed an
      increased maximal load for 105% and 235%, respectively, in rats treated with
      1,25(OH)2D3 alone, or in a combination with thyroid-stimulating hormone. We
      suggest that thyroid-stimulating hormone independently of calciotropic hormones
      suppressed bone resorption and stimulated bone formation, while in combination
      with 1,25(OH)2D3 acted synergistically on bone formation resulting in an
      increased bone volume. 

PMID- 24446159
TI  - The metabolic response to postnatal leptin in rats varies with age and may be
      litter dependent.
AB  - Hyperleptinemia during postnatal life induces long-term effects on metabolism.
      However, these effects are controversial as both increased and decreased
      propensity towards obesity has been reported. To further analyze the effects of
      chronic neonatal hyperleptinemia on the subsequent metabolic profile, male Wistar
      rats proceeding from 18 different litters (8 pups/litter) received a daily
      subcutaneous injection of either saline (10 ml/kg, n=36) or leptin (3 MUg/g,
      n=36) from postnatal day (PND) 2 to PND9. Rats were sacrificed at 10, 40, or 150
      days of age. At 10 days of age, leptin treated rats had decreased body weight
      (p<0.001) and body fat (p<0.05). Leptin levels and glycemia were increased
      (p<0.01), whereas insulin, total lipids, triglycerides and glycerol levels were
      decreased (p<0.05). At PND40 rats receiving leptin had increased glycemia
      (p<0.01) and plasma HDL and LDL levels, but decreased total lipids (p<0.05). At
      PND150 neonatal leptin treatment induced different effects in rats raised in
      different litters. Rats from litter 1 had increased body weight (p<0.05), body
      fat (p<0.01), and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride
      (p<0.001), total lipid (p<0.001), LDL (p<0.05), and glycerol (p<0.001) levels. In
      rats from litter 2 these parameters did not differ from controls. Rats from
      litter 3 had decreased body weight (p<0.05), visceral fat (p<0.01) and plasma
      leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), glycerol
      (p<0.001), and HDL (p<0.001) levels. In conclusion, the metabolic response to
      postnatal leptin varies with age, with the response in adulthood being variable
      and most likely influenced by other factors, including the genetic make-up.

PMID- 24446160
TI  - Influence of chronic exposure to cold environment on thyroid gland function in
      rabbits.
AB  - Chronic exposure to cold can affect the thyroid gland. However, the effect on
      thyroid gland perfusion images and the ratio between thyroid hormones secretion
      were not addressed in any previous study. The present study investigates the
      effects of chronic cold exposure on thyroid gland function using radionuclide
      tracer and thyroid hormones secretion concentration. New Zealand white rabbits
      weighing approximately 1.8-2 kg were kept in a cold room (4 degrees C) for 7
      weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control
      rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m
      pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera
      equipped with a low energy, high resolution, pinhole collimator interfaced with a
      computer. Static images were acquired 20 min after administration of the
      radiotracer. Rabbits chronically exposed to cold had less body weights than
      control. Thyroid gland uptake is higher in rabbits chronically exposed to cold
      than controls using radionuclide perfusion study. The increase was proportional
      to the time period, so the increase after 7 weeks was greater than 5 weeks. There
      is also an increase in free triiodothyronine (FT3) and a decrease in free
      thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher
      in rabbits chronically exposed to cold than control and the increase was
      proportional to the duration. The decrease in rabbit body weights may be related
      to the increase in metabolism due to the increase of thyroid hormones. Chronic
      cold exposure also increased the conversion of T4 to T3, which is more potent in
      thermogenic effect. 

PMID- 24446161
TI  - Insulin stimulates the expression of the SHARP-1 gene via multiple signaling
      pathways.
AB  - The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is a basic helix
      loop-helix transcription factor. An issue of whether SHARP-1 is an insulin
      inducible transcription factor was examined. Insulin rapidly increased the level
      of SHARP-1 mRNA both in vivo and in vitro. Then, signaling pathways involved with
      the increase of SHARP-1 mRNA by insulin were determined in H4IIE rat hepatoma
      cells. Pretreatments with LY294002, wortmannin, and staurosporine completely
      blocked the induction effect, suggesting the involvement of both phosphoinositide
      3-kinase (PI 3-K) and protein kinase C (PKC) pathways. In fact, overexpression of
      a dominant negative form of atypical protein kinase C lambda (aPKClambda)
      significantly decreased the induction of the SHARP-1 mRNA. In addition,
      inhibitors for the small GTPase Rac or Jun N-terminal kinase (JNK) also blocked
      the induction of SHARP-1 mRNA by insulin. Overexpression of a dominant negative
      form of Rac1 prevented the activation by insulin. Furthermore, actinomycin D and
      cycloheximide completely blocked the induction of SHARP-1 mRNA by insulin.
      Finally, when a SHARP-1 expression plasmid was transiently transfected with
      various reporter plasmids into H4IIE cells, the promoter activity of PEPCK
      reporter plasmid was specifically decreased. Thus, we conclude that insulin
      induces the SHARP-1 gene expression at the transcription level via a both PI 3
      K/aPKClambda/JNK- and a PI 3-K/Rac/JNK-signaling pathway; protein synthesis is
      required for this induction; and that SHARP-1 is a potential repressor of the
      PEPCK gene expression. 

PMID- 24446163
TI  - Osteoprotegerin in primary hyperparathyroidism.

PMID- 24446162
TI  - Circulating and urinary adrenal corticosterone, progesterone, and estradiol in
      response to acute stress in female mice (Mus musculus).
AB  - In studies of stress, it can be difficult to obtain blood rapidly enough to avoid
      confounding steroid measures. Noninvasive urinary steroid measures may provide an
      alternative insofar as they reflect systemic steroids. In Experiment 1, we
      profiled urinary corticosterone, progesterone, and estradiol in ovariectomized
      female mice following 1 h on an elevated platform. This increased urinary
      corticosterone for 3 h and progesterone for 4 h. In Experiment 2, blood and urine
      samples were obtained at 0-6 h following stressor offset. Females showed
      increased serum corticosterone and progesterone immediately after stressor
      offset. Urinary corticosterone was increased at both 0 and 2 h post-stress, while
      an increase in progesterone 2-6 h after stressor offset was not significant.
      Estradiol was not influenced by this mild stressor. In Experiment 3, mice were
      exposed to a more severe 1 h stressor, a rat across a wire-mesh grid. In serum,
      both corticosterone and progesterone were elevated immediately after stressor
      offset and returned to baseline within 2 h. In urine, this severe stressor
      elevated corticosterone immediately and 2 h after stressor offset, and in
      progesterone 2 h after stressor offset. Estradiol in serum was not dynamic, but
      it was significantly elevated in urine 4 h after stressor offset. Urinary
      measures generally reflected systemic measures; however, with a different time
      course resulting in a longer return to baseline. We suggest that the relative
      value of serum or urinary steroid measures in mice depends upon the experimental
      design, and that estradiol may only respond when the stressor is severe. 

PMID- 24446164
TI  - Quinones as dienophiles in the Diels-Alder reaction: history and applications in
      total synthesis.
AB  - In the canon of reactions available to the organic chemist engaged in total
      synthesis, the Diels-Alder reaction is among the most powerful and well
      understood. Its ability to rapidly generate molecular complexity through the
      simultaneous formation of two carbon-carbon bonds is almost unrivalled, and this
      is reflected in the great number of reported applications of this reaction.
      Historically, the use of quinones as dienophiles is highly significant, being the
      very first example investigated by Diels and Alder. Herein, we review the
      application of the Diels-Alder reaction of quinones in the total synthesis of
      natural products. The highlighted examples span some 60 years from the landmark
      syntheses of morphine (1952) and reserpine (1956) by Gates and Woodward,
      respectively, through to the present day examples, such as the tetracyclines.

PMID- 24446165
TI  - Paranodal dysmyelination in peripheral nerves of Trembler mice.
AB  - Subtle defects in paranodes of myelinated nerve fibers can cause significant
      physiological malfunction. We have investigated myelinated fibers in the
      peripheral nervous system (PNS) of the Trembler mouse, a model of CMT-1A
      neuropathy, for evidence of such defects. Ultrastructural analysis shows that the
      "transverse bands," which attach the myelin sheath to the axon at the paranodal
      axoglial junction, are grossly diminished in number in Trembler nerve fibers.
      Although paranodes often appear to be greatly elongated, it is only a short
      region immediately adjacent to the node of Ranvier that displays transverse
      bands. Where transverse bands are missing, the junctional gap widens, thus
      reducing resistance to short circuiting of nodal action currents during saltatory
      conduction and increasing the likelihood that axonal K(+) channels under the
      myelin sheath will be activated. In addition, we find evidence that structural
      domains in Trembler axons are incompletely differentiated, consistent with
      diminution in nodal Na channel density, which could further compromise
      conduction. Deficiency of transverse bands may also increase susceptibility to
      disruption of the paranodal junction and retraction of the myelin sheath. We
      conclude that Trembler PNS myelinated fibers display subtle defects in paranodal
      and nodal regions that could contribute significantly to conduction defects and
      increased risk of myelin detachment.

PMID- 24446166
TI  - Using Google AdWords for international multilingual recruitment to health
      research websites.
AB  - BACKGROUND: Google AdWords, the placement of sponsored links in Google search
      results, is a potent method of recruitment to Internet-based health studies and
      interventions. However, the performance of Google AdWords varies considerably
      depending on the language and the location of the target audience. OBJECTIVE: Our
      goal was to describe differences in AdWords performance when recruiting
      participants to the same study conducted in four languages and to determine
      whether AdWords campaigns can be optimized in order to increase recruitment while
      decreasing costs. METHODS: Google AdWords were used to recruit participants to
      the Mood Screener, a multilingual online depression screening tool available in
      English, Russian, Spanish, and Chinese. Two distinct recruitment periods are
      described: (1) "Unmanaged", a 6-month period in which ads were allowed to run
      using only the AdWords tool itself, with no human intervention, and (2)
      "Managed", a separate 7-week period during which we systematically sought to
      optimize our recruitment campaigns. RESULTS: During 6 months of unmanaged
      recruitment, our ads were shown over 1.3 million times, resulting in over 60,000
      site visits. The average click-through rate (ratio of ads clicked to ads
      displayed) varied from 1.86% for Chinese ads to 8.48% for Russian ads, as did the
      average cost-per-click (from US $0.20 for Chinese ads to US $0.50 for English
      ads). Although Chinese speakers' click-through rate was lowest, their rate of
      consenting to participate was the highest, at 3.62%, with English speakers
      exhibiting the lowest consent rate (0.97%). The conversion cost (cost to recruit
      a consenting participant) varied from US $10.80 for Russian speakers to US $51.88
      for English speakers. During the 7 weeks of "managed" recruitment, we attempted
      to improve AdWords' performance in regards to the consent rate and cost by
      systematically deleting underperforming ads and adjusting keywords. We were able
      to increase the number of people who consent after coming to the site by 91.8%
      while also decreasing per-consent cost by 23.3%. CONCLUSIONS: Our results
      illustrate the need to linguistically and culturally adapt Google AdWords
      campaigns and to manage them carefully to ensure the most cost-effective results.

PMID- 24446167
TI  - A community-based collaborative approach to improve breast cancer screening in
      underserved African American women.
AB  - Although African American women in the United States have a lower incidence of
      breast cancer compared with white women, those younger than 40 years actually
      have a higher incidence rate; additionally, African American women are more
      likely to die from breast cancer at every age compared with white women. Racial
      disparities in breast cancer mortality rates are especially significant in
      Maryland, which ranks fifth in the nation for breast cancer mortality, and in
      Baltimore City, which has the second highest annual death rate for African
      American women in Maryland. To address this disparity in care, Med-IQ, an
      accredited provider of CME, collaborated with Sisters Network Baltimore
      Metropolitan, Affiliate Chapter of Sisters Network(r) Inc., the only national
      African American breast cancer survivorship organization, to sponsor their
      community-based educational outreach initiative. The collaborative mission was to
      engage at-risk African American women, their families, local organizations,
      healthcare professionals, and clinics, with the goals of increasing awareness,
      addressing fears that affect timely care and diagnosis, and encouraging women to
      obtain regular mammograms. Intervention strategies included (1) a "Survivor
      Stories" video, (2) patient outreach consisting of neighborhood walks and an
      educational luncheon, and (3) a community outreach utilizing direct mailings to
      local businesses, community groups, and healthcare professionals. Trusted and
      well-known community resources were presented as mediums to promote the
      initiative, yielding achievement of broader and more effective outcomes. As a
      result of this patient-friendly initiative, two (2) of the women who sought
      screening were diagnosed with breast cancer and underwent treatment.

PMID- 24446168
TI  - Exchanged cations and water during reactions in polypyrrole macroions from
      artificial muscles.
AB  - The movement of the bilayer (polypyrrole-dodecylbenzenesulfonate/tape) during
      artificial muscle bending under flow of current square waves was studied in
      aqueous solutions of chloride salts. During current flow, polypyrrole redox
      reactions result in variations in the volumes of the films and macroscopic
      bending: swelling by reduction with expulsion of cations and shrinking by
      oxidation with the insertion of cations. The described angles follow a linear
      function, different in each of the studied salts, of the consumed charge: they
      are faradaic polymeric muscles. The linearity indicates that cations are the only
      exchanged ions in the studied potential range. By flow of the same specific
      charge in every electrolyte, different angles were described by the muscle. The
      charge and the angle allow the number and volume of both the exchanged cations
      and the water molecules (related to a reference) between the film to be
      determined, in addition to the electrolyte per unit of charge during the driving
      reaction. The attained apparent solvation numbers for the exchanged cations were:
      0.8, 0.7, 0.6, 0.5, 0.5, 0.4, 0.25, and 0.0 for Na(+), Mg(2+), La(3+), Li(+),
      Ca(2+), K(+), Rb(+), and Cs(+), respectively.

PMID- 24446169
TI  - Imperfect beginnings: incoming residents vary in their ability to interpret basic
      electrocardiogram findings.

PMID- 24446170
TI  - MicroRNA screen of human embryonic stem cell differentiation reveals miR-105 as
      an enhancer of megakaryopoiesis from adult CD34+ cells.
AB  - MicroRNAs (miRNAs) can control stem cell differentiation by targeting mRNAs.
      Using 96-well plate electroporation, we screened 466 human miRNA mimics by four
      color flow cytometry to explore differentiation of common myeloid progenitors
      (CMP) derived from human embryonic stem cells (hESCs). The transfected cells were
      then cultured in a cytokine cocktail that supported multiple hematopoietic
      lineages. At 4-5 days post-transfection, flow cytometry of erythroid
      (CD235(+)CD41(-)), megakaryocyte (CD41(+)CD42(+)), and myeloid (CD18(+)CD235(-))
      lineages revealed miR-105 as a novel enhancer of megakaryocyte production during
      in vitro primitive hematopoiesis. In hESC-derived CMPs, miR-105 caused a sixfold
      enhancement in megakaryocyte production. miR-513a, miR-571, and miR-195 were
      found to be less potent megakaryocyte enhancers. We confirmed the relevance of
      miR-105 in adult megakaryopoiesis by demonstrating increased megakaryocyte yield
      and megakaryocyte colony forming potential in human adult CD34(+) cells derived
      from peripheral blood. In addition, adult CD34(+) cells express endogenous miR
      105 during megakaryocyte differentiation. siRNA knockdown of the hematopoietic
      transcription factor c-Myb caused a similar enhancement of megakaryocyte
      production as miR-105. Finally, a luciferase/c-Myb-3'UTR construct and Western
      blot analysis demonstrated that the hematopoietic transcription factor c-Myb mRNA
      was a target of miR-105. We report a novel hESC-based miR screening platform and
      demonstrate that miR-105 is an enhancer of megakaryopoiesis in both primitive and
      definitive hematopoiesis.

PMID- 24446172
TI  - A dynamic model for cellulosic biomass hydrolysis: a comprehensive analysis and
      validation of hydrolysis and product inhibition mechanisms.
AB  - The objective of this study is to perform a comprehensive enzyme kinetics
      analysis in view of validating and consolidating a semimechanistic kinetic model
      consisting of homogeneous and heterogeneous reactions for enzymatic hydrolysis of
      lignocellulosic biomass proposed by the U.S. National Renewable Energy Laboratory
      (Kadam et al., Biotechnol Prog 20(3):698-705, 2004) and its variations proposed
      in this work. A number of dedicated experiments were carried out under a range of
      initial conditions (Avicel(r) versus pretreated barley straw as substrate,
      different enzyme loadings and different product inhibitors such as glucose,
      cellobiose and xylose) to test the hydrolysis and product inhibition mechanisms
      of the model. A nonlinear least squares method was used to identify the model and
      estimate kinetic parameters based on the experimental data. The suitable
      mathematical model for industrial application was selected among the proposed
      models based on statistical information (weighted sum of square errors). The
      analysis showed that transglycosylation plays a key role at high glucose levels.
      It also showed that the values of parameters depend on the selected experimental
      data used for parameter estimation. Therefore, the parameter values are not
      universal and should be used with caution. The model proposed by Kadam et al.
      (Biotechnol Prog 20(3):698-705, 2004) failed to predict the hydrolysis phenomena
      at high glucose levels, but when combined with transglycosylation reaction(s),
      the prediction of cellulose hydrolysis behaviour over a broad range of substrate
      concentrations (50-150 g/L) and enzyme loadings (15.8-31.6 and 1-5.9 mg protein/g
      cellulose for Celluclast and Novozyme 188, respectively) was possible. This is
      the first study introducing transglycosylation into the semimechanistic model. As
      long as these type of models are used within the boundary of their validity
      (substrate type, enzyme source and substrate concentration), they can support
      process design and technology improvement efforts at pilot and full-scale
      studies.

PMID- 24446171
TI  - Dysbindin-1 loss compromises NMDAR-dependent synaptic plasticity and contextual
      fear conditioning.
AB  - Genetic variants in DTNBP1 encoding the protein dysbindin-1 have often been
      associated with schizophrenia and with the cognitive deficits prominent in that
      disorder. Because impaired function of the hippocampus is thought to play a role
      in these memory deficits and because NMDAR-dependent synaptic plasticity in this
      region is a proposed biological substrate for some hippocampal-dependent memory
      functions in schizophrenia, we hypothesized that reduced dysbindin-1 expression
      would lead to impairments in NMDAR-dependent synaptic plasticity and in
      contextual fear conditioning. Acute slices from male mice carrying 0, 1, or 2
      null mutant alleles of the Dtnbp1 gene were prepared, and field recordings from
      the CA1 striatum radiatum were obtained before and after tetanization of Schaffer
      collaterals of CA3 pyramidal cells. Mice homozygous for the null mutation in
      Dtnbp1 exhibited significantly reduced NMDAR-dependent synaptic potentiation
      compared to wild type mice, an effect that could be rescued by bath application
      of the NMDA receptor coagonist glycine (10 MUM). Behavioral testing in adult mice
      revealed deficits in hippocampal memory processes. Homozygous null mice exhibited
      lower conditional freezing, without a change in the response to shock itself,
      indicative of a learning and memory deficit. Taken together, these results
      indicate that a loss of dysbindin-1 impairs hippocampal plasticity which may, in
      part, explain the role dysbindin-1 plays in the cognitive impairments of
      schizophrenia.

PMID- 24446173
TI  - Cloning, expression, purification and refolding of microtubule affinity
      regulating kinase 4 expressed in Escherichia coli.
AB  - Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4)
      is a member of the family Ser/Thr kinase and involved in numerous biological
      functions including microtubule bundle formation, nervous system development,
      positive regulation of programmed cell death, cell cycle control, cell polarity
      determination, cell shape alterations, cell division etc. For various biophysical
      and structural studies, we need this protein in adequate quantity. In this paper,
      we report a novel cloning strategy for MARK4. We have cloned MARK4 catalytic
      domain including 59 N-terminal extra residues with unknown function and catalytic
      domain alone in PQE30 vector. The recombinant MARK4 was expressed in the
      inclusion bodies in M15 cells. The inclusion bodies were solubilized effectively
      with 1.5% N-lauroylsarcosine in alkaline buffer and subsequently purified using
      Ni-NTA affinity chromatography in a single step with high purity and good
      concentration. Purity of protein was checked on sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and identified by using mass spectrometry
      immunoblotting. Refolding of the recombinant protein was validated by ATPase
      assay. Our purification procedure is quick, simple and produces adequate quantity
      of proteins with high purity in a limited step.

PMID- 24446174
TI  - Diffuse cerebral petechial hemorrhage in an 8-year-old girl with MRSA pneumonia
      and sepsis.
AB  - An 8-year-old girl in septic shock due to necrotizing methicillin-resistant
      Staphylococcus aureus (MRSA) pneumonia developed signs of end-organ damage, new
      right hemiplegia, and left gaze preference. Susceptibility-weighted MRI
      demonstrated extensive multifocal petechial hemorrhage preferentially at the gray
      white matter interface due to septic microemboli (figure). Mechanisms of
      hemorrhage include small-vessel occlusion leading to mycotic aneurysm formation
      with rupture or pyogenic arteritis without aneurysm formation.(1) Intracranial
      hemorrhage associated with metastatic staphylococcal infections is rarely
      described(2) and is especially noteworthy with diffuse cerebral petechial
      hemorrhage in the setting of metastatic MRSA. 

PMID- 24446175
TI  - The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for
      Parkinson disease.

PMID- 24446176
TI  - Restless legs syndrome and daytime sleepiness are prominent in myotonic dystrophy
      type 2.

PMID- 24446177
TI  - International issues: expanding neurologic education to resource-poor countries.
      Lessons from Moi Teaching Hospital.

PMID- 24446178
TI  - Right brain: humor completes the neurologic examination.

PMID- 24446179
TI  - Teaching neuroimages: neonatal parechovirus encephalitis: typical MRI findings.
AB  - A full-term 9-day-old girl presented with fever, irritability, and seizures. The
      routine CSF examination, cranial ultrasound, and laboratory tests were normal.
      Brain MRI showed diffuse white matter abnormality (figure). Human parechovirus
      (HPeV) type 3 was isolated in both CSF and blood. The neurodevelopmental outcome
      at 4 months is poor, and MRI shows an extensive cystic leukomalacia in the
      frontal white matter. 

PMID- 24446180
TI  - Gene-environment interactions on the risk of esophageal cancer among Asian
      populations with the G48A polymorphism in the alcohol dehydrogenase-2 gene: a
      meta-analysis.
AB  - The aim of this study is to investigate the gene-environment interactions between
      the G48A polymorphism in the alcohol dehydrogenase-2 (ADH2) gene and
      environmental factors in determining the risk of esophageal cancer (EC). A
      literature search was conducted in the PubMed, Embase, Web of Science, Cochrane
      Library, and Google Scholar databases to indentify eligible studies published
      before November 1, 2013. We performed a meta-analysis of 18 case-control studies
      with a total of 8,906 EC patients and 13,712 controls. The overall analysis
      suggested that individuals with the GG genotype were associated with a 2.77-fold
      increased risk of EC, compared with carriers of the GA and AA genotypes. In a
      stratified analysis by ethnic group, Japanese, Mainland Chinese, and Taiwan
      Chinese with the GG genotype had a significantly higher risk of EC, compared with
      Thai and Iranian populations, indicating ethnic variance in EC susceptibility. An
      analysis of combined effect indicated that GG genotype of ADH2 G48A was
      associated with the highest risk of EC in heavy drinkers and smokers. A striking
      difference was found to exist between males and females, showing gender variance
      for the association between ADH2 G48A and EC risk. This meta-analysis shows that
      the GG genotype of ADH2 G48A may be associated with an increased risk of EC in
      Asian populations. In addition, significant gene-environment interactions were
      found. Heavy drinkers, smokers, and males with the GG genotype may have a higher
      EC risk. Thus, our results shed new light on the complex gene-environment
      interactions that exist between environmental factors and ADH2 G48A polymorphism
      in EC risk. 

PMID- 24446181
TI  - MicroRNA-21 is a novel promising target in cancer radiation therapy.
AB  - MicroRNAs (miRNAs) represent an important nonprotein part of the human genome in
      tumor biology. Among the several types of miRNAs, microRNA-21 (miR-21) is
      dysregulated in several types of cancer and plays a key role in carcinogenesis,
      recurrence, and metastasis. Thus, it can be a potential target for cancer therapy
      including radiation therapy. In this review, we focus on miR-21, which has been
      identified in human cancer tissues, to suggest reasonable strategies for future
      research. miR-21 may have an influence on cell cycle, DNA damage repair,
      apoptosis, autophagy, and hypoxia of cancer during irradiation. We review the use
      of miR-21 in cancer radiation therapy and describe the known functions and
      possible underlying molecular mechanisms of miR-21 in radiosensitivity and
      radioresistance. Furthermore, the current and potential future applications of
      miR-21 in cancer radiation therapy are also discussed. 

PMID- 24446182
TI  - Correlation between genetic polymorphisms within IL-1B and TLR4 genes and cancer
      risk in a Russian population: a case-control study.
AB  - In the last decade, a growing interest has been devoted to the evaluation of the
      impact of single nucleotide polymorphisms (SNP) on cancer risk. According to the
      results of multiple studies, among the genes that have a considerable influence
      on cancer risk are those encoding pattern recognition receptors, cytokines, and
      antioxidant defense enzymes. Nonetheless, the effect of numerous SNPs within
      these genes on cancer risk has been scarcely investigated. A case-control study
      of 401 cases and 300 sex- and age-matched controls was performed in order to
      explore the role of IL1B_1473G/C (rs1143623), SOD1_7958A/G (rs4998557),
      TLR4_1196C/T (rs4986791), IL10_1082A/G (rs1800896), IL17A_197G/A (rs2275913), and
      TLR4_896A/G (rs4986790) polymorphisms in the susceptibility to colorectal cancer
      (n = 244), gastric carcinoma (n = 72), and ovarian cancer (n = 85). The analysis
      revealed a significant relationship between the presence of heterozygous
      genotypes for IL1B_1473G/C and TLR4_896A/G polymorphisms and higher risk of
      rectal cancer (codominant model, OR = 1.67; 95% CI, 1.06-2.63; p = 0.048 and OR =
      2.25; 95% CI, 1.26-4.02; p = 0.014, respectively). In addition, the variant G/G
      genotype of the IL10_1082A/G SNP was associated with a 2.5-fold increase in
      ovarian cancer risk with a borderline significance (codominant model, OR = 2.45;
      95% CI, 1.14-5.25; p = 0.069). Similarly, the carriers of the C/T genotype for
      the TLR4_1196C/T polymorphism were more susceptible to rectal cancer with a
      borderline significance (codominant model, OR = 1.42; 95% CI, 0.80-2.51 p =
      0.06). No statistically significant associations were found when stratifying the
      sample by subgroups of age, sex, and clinicopathological characteristics.
      Finally, we observed six combinations of haplotypes for the examined SNPs, each
      of which either profoundly increased or decreased cancer risk. The results from
      our study provided evidence that IL1B_1473G/C and TLR4_896A/G SNPs are implicated
      in rectal cancer development in a Russian population. Further research should be
      addressed to clarify the role of the abovementioned polymorphisms in cancer
      etiology.

PMID- 24446184
TI  - [Managing emotions--emotions under control].
AB  - Emotion regulation processes are of central importance to mental and physical
      health. Based on this relationship we developed the group intervention "Managing
      Emotions: Emotions under control" (German: "Gefuhle im Griff"), which
      systematically teaches participants specific emotion regulation strategies.
      Structure and content of the intervention program as well as preliminary results
      of efficacy are presented (n=18). Using the H-FERST, large effect sizes resulted
      for the increase of reappraisal and acceptance and for the reduction of
      rumination, a medium effect size could be shown for the reduction of avoidance,
      and a small effect size resulted for the increase of activity and social support.
      Overall psychopathology by means of the BSI was reduced with an effect size of
      d=0.63 in participants with more severe mental strain (GSI >= 0.6).

PMID- 24446185
TI  - [Interpersonal patterns in obese patients].
AB  - In the last decades the number of obese and pre-obese patients in Western
      industrial nations increased. Obese patients have been largely unsuccessful in
      losing weight over time, but the causes of their difficulties and the causes of
      their obesity have remained unclear. We examined whether the attachment style and
      its interaction with interpersonal processes would shed light on this question.
      We analyzed 107 obese or pre-obese patients before the start of a weight loss
      intervention program. We used the Adult Attachement Prototype Rating (AAPR)
      interview and related questionnaires (Helping Alliance Questionnaire (HAQ),
      Inventory of Interpersonal Problems (IIP-D), Brief Symptom Inventory (BSI)).
      According to the AAPR-rating 54% of the patients were secure and 46% insecure
      attached. The results suggest that insecure attachment style has an impact on
      psychic strain in obese patients unrelated to weight, gender and age.
      Additionally the insecure attachment style influences the therapeutic alliance
      experienced by patients and the therapist.

PMID- 24446183
TI  - Alterations of the lung methylome in allergic airway hyper-responsiveness.
AB  - Asthma is a chronic airway disorder characterized by recurrent attacks of
      breathlessness and wheezing, affecting 300 million people around the world
      (available at: www.who.int). To date, genetic factors associated with asthma
      susceptibility have been unable to explain the full etiology of asthma. Recent
      studies have demonstrated that the epigenetic disruption of gene expression plays
      an equally important role in the development of asthma through interaction with
      our environment. We sensitized 6-week-old C57BL/6J mice with house-dust-mite
      (HDM) extracts intraperitoneally followed by 5 weeks of exposure to HDM
      challenges (three times a week) intratracheally. HDM-exposed mice showed an
      increase in airway hyper-responsiveness (AHR) and inflammation together with
      structural remodeling of the airways. We applied methylated DNA
      immunoprecipitation-next generation sequencing (MeDIP-seq) for profiling of DNA
      methylation changes in the lungs in response to HDM. We observed about 20 million
      reads by a single-run of massive parallel sequencing. We performed bioinformatics
      and pathway analysis on the raw sequencing data to identify differentially
      methylated candidate genes in HDM-exposed mice. Specifically, we have revealed
      that the transforming growth factor beta signaling pathway is epigenetically
      modulated by chronic exposure to HDM. Here, we demonstrated that a specific
      allergen may play a role in AHR through an epigenetic mechanism by disrupting the
      expression of genes in lungs that might be involved in airway inflammation and
      remodeling. Our findings provide new insights into the potential mechanisms by
      which environmental allergens induce allergic asthma and such insights may assist
      in the development of novel preventive and therapeutic options for this
      debilitative disease.

PMID- 24446186
TI  - [The role of stress axes in cancer incidence and proliferation].
AB  - Psychosocial stressors can modulate the different stages of neoplastic events. It
      is established that there is activation of 2 well-known stress axes under stress,
      the hypothalamic-pituitary-adrenal axis and sympatho-adrenal-medullary axis,
      where especially the proliferating promoting effects on the malignant tumor
      events are known to depend on beta-adrenergic receptors. A new model focuses on
      the positive activating stress, which leads through the activation of the
      sympathetic hypothalamic-adipocyte axis to inhibition of tumor growth and
      reduction of obesity. This leads in mice to increased gene expression of the
      neurotrophin BDNF, which activates the sympathetic fibers of the white adipose
      tissue. Over consecutive stimulation of the beta-adrenergic receptors and thus
      the release of leptin, its promotional effect on the tumor growth is inhibited.
      In the clinical context, these results support the role of complex beta
      adrenergic signal transduction pathways. 

PMID- 24446187
TI  - A role for microglial cells in reshaping neuronal circuitry of the adult rat
      auditory brainstem after its sensory deafferentation.
AB  - Cochlear ablation triggers cellular and molecular reactions in the adult
      mammalian central auditory system, leading to complex rearrangements in the
      cellular networks of the auditory brainstem. The role of microglial cells in
      these processes is largely unknown. We analyzed morphological and molecular
      responses as well as cellular affiliations of microglia in the auditory brainstem
      1 and 7 days after unilateral sensory deafferentation of the cochlear nucleus. In
      the ventral cochlear nucleus (VCN), morphological changes of microglial cells
      were evident following cochlear ablation. Microglial activation preceded
      astroglial hypertrophy in VCN and lateral superior olive (LSO). During axonal
      degeneration in VCN early after cochlear ablation, p-ERK1/2- and p-p38
      immunoreactive microglia displayed a hypertrophied phenotype, with processes
      partially surrounding glutamatergic but not GABAergic synapses. During the peak
      of VCN reinnervation 1 week after cochlear ablation, the number of microglial
      cells increased massively. Microglia now displayed dense ramifications juxtaposed
      to Gap43-immunoreactive axons and their terminals. Moreover, we identified lesion
      dependent changes in the populations of microglia and astrocytes in LSO and
      inferior colliculus. By covisualizing cytological markers such as NeuN, GFAP,
      CD11b, vGluT-1, GAD-65, and Gap43 with the prominent MAP kinases ERK1/2 and p38,
      we show that MAPK signaling is affected by sensory deafferentation in microglia
      but not in astroglia or in neurons. In conclusion, microglia displaying MAPK
      signaling appear to contribute to an adaptive response in central auditory
      regions that was directly or indirectly affected by sensory deafferentation.
      Moreover, microglial cells are temporally and spatially in place to participate
      in synaptogenesis inside VCN.

PMID- 24446188
TI  - One-pot semisynthesis of exon 1 of the Huntingtin protein: new tools for
      elucidating the role of posttranslational modifications in the pathogenesis of
      Huntington's disease.
AB  - The natural enzymes involved in regulating many of the posttranslational
      modifications (PTMs) within the first 17 residues (Nt17) of Huntingtin exon 1
      (Httex1) remain unknown. A semisynthetic strategy that allows the site-specific
      introduction of PTMs within Nt17 by using expressed protein ligation (EPL) was
      developed. This strategy was used to produce untagged wild-type (wt) and T3
      phosphorylated (pT3) Httex1 containing 23 glutamine residues (Httex1-23Q). Our
      studies show that pT3 significantly slows the oligomerization and fibrillization
      of Httex1-23Q and that Httex1 variants containing polyQ repeats below the
      pathogenic threshold readily aggregate and form fibrils in vitro. These findings
      suggest that crossing the polyQ pathogenic threshold is not essential for Httex1
      aggregation. The ability to produce wt or site-specifically modified tag-free
      Httex1 should facilitate determining its structure and the role of N-terminal
      PTMs in regulating the functions of Htt in health and disease. 

PMID- 24446189
TI  - Interface stability of a TiO2/3-methoxypropionitrile-based electrolyte: first
      evidence for solid electrolyte interphase formation and implications.
AB  - We report an in-depth study focusing on the stability of a benchmark electrolyte
      composition based on a low-volatile 3-methoxypropionitrile (MPN) solvent employed
      in dye-sensitized solar cells. In the presence of TiO2, the semi-conductor
      surface plays a catalytic role in the thermal degradation of the electrolyte,
      which induces, among other effects, the nucleation and growth of a uniform solid
      electrolyte interphase (SEI) layer that wraps TiO2. On the basis of our actual
      understanding, we argue that SEI formation is responsible for triiodide depletion
      in the electrolyte during ageing and also has a simultaneous impact on TiO2
      optoelectronic properties through the onset of a visible-light absorption tail,
      energy modification of intraband trap states, and the induction of an increase in
      both electron lifetime and transport time in TiO2. In-depth characterization of
      this layer by using XPS and ToF-SIMS indicates that the chemical composition of
      this SEI results from solvent and additive degradation, that is, iodide, sulfur,
      cyano, nitrogen, carbon, and imidazolium rings. The SEI thickness, its content,
      and the concentration profile strongly vary depending on the ageing conditions.
      The outcome of this new finding is discussed in comparison with literature
      observations and stresses the difficulties in reaching long-term stability at 85 
      degrees C by using MPN-based electrolytes unless new interfacial engineering is
      accomplished to impede pinholes between dye molecules on TiO2.

PMID- 24446190
TI  - Hematopoietic stem/progenitor cells express myoglobin and neuroglobin: adaptation
      to hypoxia or prevention from oxidative stress?
AB  - Oxidative metabolism and redox signaling prove to play a decisional role in
      controlling adult hematopoietic stem/progenitor cells (HSPCs) biology. However,
      HSPCs reside in a hypoxic bone marrow microenvironment raising the question of
      how oxygen metabolism might be ensued. In this study, we provide for the first
      time novel functional and molecular evidences that human HSPCs express myoglobin
      (Mb) at level comparable with that of a muscle-derived cell line. Optical
      spectroscopy and oxymetry enabled to estimate an O2-sensitive heme-containing
      protein content of approximately 180 ng globin per 10(6) HSPC and a P50 of
      approximately 3 uM O2. Noticeably, expression of Mb mainly occurs through a HIF-1
      induced alternative transcript (Mb-V/Mb-N = 35 +/- 15, p < .01). A search for
      other Mb-related globins unveiled significant expression of neuroglobin (Ngb) but
      not of cytoglobin. Confocal microscopy immune detection of Mb in HSPCs strikingly
      revealed nuclear localization in cell subsets expressing high level of CD34
      (nuclear/cytoplasmic Mb ratios 1.40 +/- 0.02 vs. 0.85 +/- 0.05, p < .01) whereas
      Ngb was homogeneously distributed in all the HSPC population. Dual-color
      fluorescence flow cytometry indicated that while the Mb content was homogeneously
      distributed in all the HSPC subsets that of Ngb was twofold higher in more
      immature HSPC. Moreover, we show that HSPCs exhibit a hypoxic nitrite reductase
      activity releasing NO consistent with described noncanonical functions of
      globins. Our finding extends the notion that Mb and Ngb can be expressed in
      nonmuscle and non-neural contexts, respectively, and is suggestive of a
      differential role of Mb in HSPC in controlling oxidative metabolism at different
      stages of commitment.

PMID- 24446191
TI  - Effects of supplemental vitamin C and chromium on metabolic and hormonal
      responses, antioxidant status, and tonic immobility reactions of transported
      broiler chickens.
AB  - Three hundred female broilers were assigned to five groups with six replicates
      and were fed with either a basal diet (two control groups) or the basal diet
      supplemented with 800-mg vitamin C/kg (Vit C group), 1,200-MUg Cr(+3) from
      chromium (Cr) chloride/kg (Cr group) or 800-mg Vit C and 1,200-MUg Cr(+3) from Cr
      chloride/kg (Vit C + Cr group) from 42 to 49 days of age. Treatments did not
      affect performance. Transport decreased insulin level in the control and Cr
      groups and increased glucose/insulin (G/I) ratio in the groups. The level of
      insulin was higher in the Vit C + Cr group than those in the control and Cr
      groups after the transport. The G/I ratio was lowest in the Vit C + Cr group
      after the transport. The transport significantly decreased triiodothyronine (T3)
      concentration in the groups except the Vit C + Cr group and only increased
      thyroxin (T4) concentration in the Vit C + Cr group. The T3/T4 ratio was
      significantly decreased in the groups except the Cr group by transport. The T3/T4
      ratio was greatest in the Vit C + Cr group before the transport. Alkaline
      phosphatase activity was decreased in the Vit C + Cr group due to transport.
      Transport decreased triglyceride levels in the groups and also decreased low
      density lipoprotein cholesterol levels in the Vit-C-supplemented groups.
      Transport increased malondialdehyde concentration in the control and Vit C groups
      and also increased glutathione peroxidase (GPx) activity in the Cr-fed groups.
      The GPx activity was higher in the Vit C + Cr group than those in the control and
      Cr groups after the transport. Ferric reducing/antioxidant power (FRAP) value was
      decreased in the Vit C and Cr groups by transport. Either alone or in
      combination, Cr increased the FRAP value before the transport. Neither transport
      nor treatments had significant effects on the duration of tonic immobility (TI)
      and number of inductions to induce TI.

PMID- 24446192
TI  - Is the hypoglycemic action of vanadium compounds related to the suppression of
      feeding?
AB  - Vanadium compounds exhibit effective hypoglycemic activity in both type I and
      type II diabetes mellitus. However, there was one argument that the hypoglycemic
      action of vanadium compounds could be attributable to the suppression of feeding
      one common toxic aspect of vanadium compounds. To clarify this question, we
      investigated in this work the effect of a vanadyl complex, BSOV (bis((5-hydroxy-4
      oxo-4H-pyran-2-yl)methyl-2-hydroxy-benzoatato) oxovanadium (IV)), on diabetic
      obese (db/db) mice at a low dose (0.05 mmol/kg/day) when BSOV did not inhibit
      feeding. The experimental results showed that this dose of BSOV effectively
      normalized the blood glucose level in diabetic mice without affecting the body
      weight growth. Western blotting assays on the white adipose tissue of db/db mice
      further indicated that BSOV treatment significantly improved expression of
      peroxisome proliferator-activated receptor gamma (PPARgamma) and activated AMP
      activated protein kinase (AMPK). In addition, vanadium treatment caused a
      significant suppression of phosphorylation of c-Jun N-terminal protein kinase
      (JNK), which plays a key role in insulin-resistance in type II diabetes. This is
      the first evidence that the mechanism of insulin enhancement action involves
      interaction of vanadium compounds with JNK. Overall, the present work indicated
      that vanadium compounds exhibit antidiabetic effects irrelevant to food intake
      suppression but by modulating the signal transductions of diabetes and other
      metabolic disorders.

PMID- 24446193
TI  - Mineral levels in Pyrenean chamois (Rupicapra pyrenaica).
AB  - The effects of mineral deficiencies are often sub-clinical, and the importance of
      mineral status is often underestimated in wildlife populations. To our knowledge,
      this is the first study that gives reference intervals of hepatic minerals for
      Pyrenean chamois (Rupicapra pyrenaica). We determined macro and trace mineral
      concentrations in liver samples from 100 animals (44 healthy and 56 sick)
      collected in the Catalan Pyrenees (NE Spain) from 1995 to 2008. After wet
      digestion, we determined Na, K, Ca, P, Mg, S, and Fe concentrations by
      inductively coupled plasma optical emission spectrometry (ICP-OES) and Cu, Zn,
      and Mo concentrations by inductively coupled plasma mass spectrometry (ICP-MS).
      We observed low hepatic concentrations of Cu in a considerable percentage of
      chamois, without evidences that these low concentrations increased their
      susceptibility to infectious diseases. The group of sick chamois had very similar
      percentage of animals (10/56) with low concentration of Cu (<20 ppm DW) than the
      group of healthy chamois (9/44). On the other hand, we observed that infectious
      diseases increased significantly the hepatic concentrations of Na, Ca, Mg, Fe and
      Zn, very likely, as a consequence of processes associated with the acute phase
      inflammatory response. The obtained values of liver mineral levels and their
      sources of variation, such as sex, age and disease, mostly fall within the range
      of those described for other ruminants, but possible deficiencies and differences
      between individuals and populations require further study.

PMID- 24446194
TI  - Dielectric pads and low- B1+ adiabatic pulses: complementary techniques to
      optimize structural T1 w whole-brain MP2RAGE scans at 7 tesla.
AB  - PURPOSE: To evaluate the combination of low-B1 (+) adiabatic pulses and high
      permittivity (epsilonr ~ 165) dielectric pads effectiveness to reproducibly
      improve the inversion efficiency for whole-brain MP2RAGE scans, at ultra-high
      field. MATERIALS AND METHODS: Two low-B1 (+) adiabatic pulses, HS8 and TR-FOCI,
      were compared with the conventional HS1 adiabatic pulse in MP2RAGE acquisitions
      of four subjects at 7 Tesla. The uniform MP2RAGE images were qualitatively
      assessed for poor inversion artifacts by trained observers. Each subject was
      rescanned using dielectric pads. Eight further subjects underwent two MP2RAGE
      scan sessions using dielectric pads and the TR-FOCI adiabatic pulse. RESULTS: The
      HS8 and TR-FOCI pulses improved inversion coverage in all subjects compared with
      the HS1 pulse. However, in subjects whose head lengths are large (>=136 mm)
      relative to the coil's z-coverage, the B1 (+) field over the cerebellum was
      insufficient to cause inversion. Dielectric pads increase the B1 (+) field, by
      ~50%, over the cerebellum, which in conjunction with the TR-FOCI pulse,
      reproducibly improves the inversion efficiency over the whole brain for subjects
      with head lengths <=155 mm. Minor residual inversion artifacts were present in
      three of eight subjects (head lengths >=155 mm). CONCLUSION: The complementary
      techniques of low-B1 (+) adiabatic RF pulses and high permittivity dielectric
      pads allow whole-brain structural T1 w images to be reliably acquired at ultra
      high field. J. Magn. Reson. Imaging 2014;40:804-812. (c) 2013 Wiley Periodicals,
      Inc.

PMID- 24446195
TI  - How do supervising physicians decide to entrust residents with unsupervised
      tasks? A qualitative analysis.
AB  - BACKGROUND: Medical supervisors struggle to find meaningful ways to evaluate the
      preparedness of trainees to independently perform patient care tasks. The aim of
      this study was to describe the factors that influence how attending and resident
      physician perceptions of trust impact decision making. METHODS: Internal medicine
      residents and attending physicians at a tertiary academic medical center were
      interviewed during a single academic year. Participants were asked to describe,
      using the critical incident technique, entrustment decisions made during their
      clinical rotations. A deductive qualitative analysis using the entrustable
      professional activities framework was used. The inter-rater reliability was
      calculated using a generalized kappa statistic. RESULTS: Eighty-four percent
      (46/50) of residents and 88% (44/50) of attending physicians participated. The
      analysis yielded 535 discrete mentions of entrusting factors that were mapped to
      the following domains deductively, with inductively derived subthemes: trainee
      factors (eg, confidence, specialty plans), supervisor factors (eg,
      approachability), task factors (eg, situational characteristics) and systems
      factors (eg, workload). The inter-rater kappa between the 2 raters was 0.84.
      CONCLUSIONS: Factors influencing trust in a trainee are related to the
      supervisor, trainee, their relationship, task, and the environment. Attending
      physicians note early interactions and language cues as markers of
      trustworthiness. Attending physicians reported using perceived confidence as a
      gauge of the trainee's true ability and comfort. Attendings noted trainee
      absences, even those that comply with regulation, negatively affected willingness
      to entrust. Future studies are needed to develop better assessment instruments to
      understand how entrustment decisions for independent practice are made.

PMID- 24446196
TI  - Mathematical model of liver regeneration in human live donors.
AB  - Liver regeneration after injury occurs in many mammals. Rat liver regenerates
      after partial hepatectomy over a period of 2 weeks while human liver regeneration
      takes several months. Notwithstanding this enormous difference in time-scales,
      with new data from five human live liver transplant donors, we show that a
      mathematical model of rat liver regeneration can be transferred to human, with
      all biochemical interactions and signaling unchanged. Only six phenomenological
      parameters need change, and three of these parameter changes are rescalings of
      rate constants by the ratio of human lifespan to rat lifespan. Data from three
      donor subjects with approximately equal resections were used to fit the three
      parameters and the data from the other two donor subjects was used to
      independently verify the fit.

PMID- 24446198
TI  - Endocan elicits severe vascular inflammatory responses in vitro and in vivo.
AB  - Endocan is a proteoglycan secreted by endothelial cells under the control of
      inflammatory cytokines. The aim of this study was to evaluate the effects of
      endocan on proinflammatory responses and on septic mice and underlying
      mechanisms. Human umbilical vein endothelial cells (HUVECs) or mice were exposed
      to lipopolysaccharide (LPS) or endocan with or without neutralizing endocan
      antibody. Mice were subjected to cecal ligation and puncture (CLP) surgery with
      or without neutralizing endocan antibody. Endocan was highly released by LPS and
      it enhanced proinflammatory responses. In a CLP-induced sepsis model, endocan was
      also highly released, but this release was prevented by administration of
      neutralizing endocan antibody. Circulating levels of endocan measured in patients
      admitted to the intensive care unit with sepsis were significantly elevated
      compared with control donors. Furthermore, the administration of endocan antibody
      reduced CLP-induced sepsis mortality. This study shows endocan can elicit severe
      inflammatory responses and inhibiting endocan release offers a potential strategy
      for treating sepsis.

PMID- 24446197
TI  - Adaptive responses of mitochondria to mild copper deprivation involve changes in
      morphology, OXPHOS remodeling and bioenergetics.
AB  - Copper is an essential cofactor of complex IV of the electron transfer chain, and
      it is directly involved in the generation of mitochondrial membrane potential.
      Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus,
      there is a connection between copper metabolism and bioenergetics, mitochondrial
      dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or
      necrosis. However, before entering into those irreversible processes,
      mitochondria may execute a series of adaptive responses. Mitochondrial adaptive
      responses (MAR) may involve multiple and diverse mechanisms for preserving cell
      life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output.
      In this study, a mild copper deficiency was produced in an animal model through
      intraperitoneal injections of bathocuproine disulfonate in order to study the
      MAR. Under these conditions, a new type of mitochondrial morphology was
      discovered in the liver. Termed the "butternut squash" mitochondria, it coexisted
      with normal and swollen mitochondria. Western blot analyses of mitochondrial
      dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins.
      Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a
      decrease in supercomplex activity with a concomitant increase at an individual
      level of complexes I and IV, higher respiratory rates at complex I and II levels,
      higher oligomycin-insensitive respiration, and lower respiratory control ratio
      values when compared to the control group. As expected, total ATP and ATP/ADP
      values were not significantly different, since animal's health was not
      compromised. As a whole, these results describe a compensatory and adaptive
      response of metabolism and bioenergetics under copper deprivation.

PMID- 24446199
TI  - TNF-alpha upregulates sclerostin expression in obese mice fed a high-fat diet.
AB  - Sclerostin decreases bone mass by antagonizing the Wnt signaling pathway. We
      examined whether obesity-induced bone loss is associated with the expression of
      sclerostin. Five-week-old male mice were assigned to one of two groups (n = 10
      each) and fed either a control diet (10% kcal from fat; CON) or a high-fat diet
      (60% kcal from fat; HF) for 12 weeks. Thex final body weight and whole body fat
      mass of the HF mice were higher than those of the CON mice. The distal femur
      cancellous bone mineral density and bone formation rate was lower in HF mice than
      in CON mice. The percent erosion surface was higher in the HF mice than the CON
      mice. The serum levels and femoral osteocytic protein expression levels of tumor
      necrosis factor-alpha (TNF-alpha) were significantly higher in HF mice than in
      CON mice. Sclerostin mRNA levels and osteocytic sclerostin protein levels in
      femoral cortex were also higher in HF mice than in CON mice. Sclerostin
      expression in MLO-Y4 osteocytes increased with TNF-alpha treatment, and TNF-alpha
      induced sclerostin expression was blocked by the inhibition of NF-kappaB
      activation. Chromatin immunoprecipitation and a luciferase reporter assay
      demonstrated that NF-kappaB directly binds to the NF-kappaB binding elements on
      the mouse sost promoter and stimulates sclerostin expression. These results
      support a model in which, in the context of obesity or other inflammatory
      diseases that increase the production of TNF-alpha, TNF-alpha upregulates the
      expression of sclerostin through NF-kappaB signaling pathway, thus contributing
      to bone loss.

PMID- 24446200
TI  - Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.
AB  - Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic
      liver disease and Wnt/beta-catenin signaling plays a crucial role in the
      expansion of HPCs. However, the molecular mechanisms that regulate the activation
      of Wnt/beta-catenin signaling in the liver, especially in HPCs, remain largely
      elusive. Here, we reported that ectopic expression of Smad6 suppressed the
      proliferation and self-renewal of WB-F344 cells, a HPC cell line.
      Mechanistically, we found that Smad6 inhibited Wnt/beta-catenin signaling through
      promoting the interaction of C-terminal binding protein (CtBP) with beta
      catenin/T-cell factor (TCF) complex to inhibit beta-catenin mediated
      transcriptional activation in WB-F344 cells. We used siRNA targeting beta-catenin
      to demonstrate that Wnt/beta-catenin signaling was required for the proliferation
      and self-renewal of HPCs. Taken together, these results suggest that Smad6 is a
      regulatory molecule which regulates the proliferation, self-renewal and Wnt/beta
      catenin signaling in HPCs.

PMID- 24446204
TI  - Synthesis and antinociception activity of new substituted phenothiazines and
      ethylenediamines as antihistaminic drugs.
AB  - Antihistamines play an important role in medicine when it comes to relieving
      seasonal or non-seasonal rhinitis, the common cold, and itching. They have also
      shown many various combinations of pharmacological properties such as anti
      inflammatory and analgesic activities. Phenothiazines and ethylenediamines are 2
      important classes of antihistamines with analgesic activities in addition to
      other pharmacological effects. In this study, some new derivatives of these
      compounds (V-IX) were synthesized and their antinociceptive behaviors were
      examined by pharmacological tests. The results indicated that new analogue with
      methyl groups produced a better analgesic activity than chlorine atoms but less
      than III (without any substitutions) in ethylenediamine class. Also in
      phenothiazine class, adding pyrimidine and pyridine substituted showed the better
      analgesic activity compared to other groups. Moreover, the analgesic activities
      proved that dimethylamine is the best group in amino alkyl side chain of these
      molecules relative to the substituted piperazines in new analogues. 

PMID- 24446205
TI  - Synthesis and antitubercular activity of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole
      derivatives.
AB  - Novel 3,5-diaryl-4,5-dihydro-1H-pyrazole derivatives were efficiently synthesized
      and evaluated for their in vitro antitubercular activity against Mycobacterium
      tuberculosis H37Rv (MTB). The chemical structures of the compound were elucidated
      by elemental analysis, FTIR, (1)H NMR, and mass spectral data. Most of the title
      compounds have exhibited significant antitubercular activity. Compounds 4g, 4h,
      4l, 4n and 4o showed pronounced antitubercular activity comparable to the
      reference isoniazid, whereas, compounds 4a, 4c, 4j, 4k, and 4p displayed good
      antitubercular activity. 5-(4-chlorophenyl)-4,5-dihydro-3-p-tolylpyrazol-1-yl-(6
      methylimidazo[2,1-b]thiazol-5-yl)methanone (4g) was found to be the most
      promising compound with MIC values of 0.39 ug/ml. 

PMID- 24446206
TI  - Non-carboxylic analogues of aryl propionic acid: synthesis, anti-inflammatory,
      analgesic, antipyretic and ulcerogenic potential.
AB  - As a part of ongoing studies in developing new potent anti-inflammatory and
      analgesic agents, a series of novel 6-methoxy naphthalene derivatives was
      efficiently synthesized and characterized by spectral and elemental analyses. The
      newly synthesized compounds were evaluated for their anti-inflammatory activities
      using carrageenin-induced rat paw edema model, analgesic activities using acetic
      acid induced writhing model in mice and anti-pyretic activity using yeast induced
      hyperpyrexia method as well as ulcerogenic effects. Among the synthesized
      compounds, thiourea derivative (6a, e) exhibited higher anti-inflammatory
      activity than the standard drug naproxen in reduction of the rat paw edema
      (88.71, 89.77%) respectively. All of the non-carboxylic tested compounds were
      found to have promising anti-inflammatory, analgesic and antipyretic activity,
      while were devoid of any ulcerogenic effects.

PMID- 24446207
TI  - Exchange of methyl- and azobenzene-terminated alkanethiols on polycrystalline
      gold studied by tip-enhanced Raman mapping.
AB  - Mixed thiol self-assembled monolayers (SAMs) presenting methyl and azobenzene
      head groups were prepared by chemical substitution from the original single
      component n-decanethiol or [4-(phenylazo)phenoxy]hexane-1-thiol SAMs on
      polycrystalline gold substrates. Static contact-angle measurements were carried
      out to confirm a change in the hydrophobicity of the functionalized surfaces
      following the exchange reaction. The mixed SAMs presented contact-angle values
      between those of the more hydrophobic n-decanethiol and the more hydrophilic [4
      (phenylazo)phenoxy]hexane-1-thiol single-component SAMs. By means of tip-enhanced
      Raman spectroscopy (TERS) mapping experiments, it was possible to highlight that
      molecular replacement takes place easily and first at grain boundaries: for two
      different mixed SAM compositions, TERS point-by-point maps with <50 nm step sizes
      showed different spectral signatures in correspondence to the grain boundaries.
      An example of the substitution extending beyond grain boundaries and affecting
      flat areas of the gold surface is also shown. 

PMID- 24446208
TI  - Fluorine in shark teeth: its direct atomic-resolution imaging and strengthening
      function.
AB  - Atomic-resolution imaging of beam-sensitive biominerals is extremely challenging,
      owing to their fairly complex structures and the damage caused by electron
      irradiation. Herein, we overcome these difficulties by performing aberration
      corrected electron microscopy with low-dose imaging techniques, and report the
      successful direct atomic-resolution imaging of every individual atomic column in
      the complex fluorapatite structure of shark tooth enameloid, which can be of
      paramount importance for teeth in general. We demonstrate that every individual
      atomic column in shark tooth enameloid can be spatially resolved, and has a
      complex fluorapatite structure. Furthermore, ab initio calculations show that
      fluorine atoms can be covalently bound to the surrounding calcium atoms, which
      improves understanding of their caries-reducing effects in shark teeth. 

PMID- 24446209
TI  - Influence of APOE genotype and the presence of Alzheimer's pathology on synaptic
      membrane lipids of human brains.
AB  - The APOE genotype is the major risk factor for Alzheimer's disease (AD); however,
      it remains unclarified how the epsilon4 allele accelerates whereas the epsilon2
      allele suppresses AD development, compared with the more common epsilon3 allele.
      On the basis of the previous finding that the assembly of the amyloid-beta
      protein (Abeta) into fibrils in the brain, an early and invariable pathological
      feature of AD, depends on the lipid environment, we determined the levels of
      synaptic membrane lipids in aged individuals of different APOE genotypes. In the
      comparison between amyloid-free epsilon2/epsilon3 and epsilon3/epsilon3 brains,
      the presence of the epsilon2 allele significantly decreased the level of
      cholesterol. Alternatively, in the comparison among epsilon3/epsilon3 brains, the
      presence of AD pathology substantially decreased the levels of cholesterol. This
      study suggests that the epsilon2 allele suppresses the initiation of AD
      development by lowering the cholesterol levels in synaptic membranes.

PMID- 24446210
TI  - Bone environment is essential for osteosarcoma development from transformed
      mesenchymal stem cells.
AB  - The cellular microenvironment plays a relevant role in cancer development. We
      have reported that mesenchymal stromal/stem cells (MSCs) deficient for p53 alone
      or together with RB (p53(-/-)RB(-/-)) originate leiomyosarcoma after subcutaneous
      (s.c.) inoculation. Here, we show that intrabone or periosteal inoculation of
      p53(-/-) or p53(-/-)RB(-/-) bone marrow- or adipose tissue-derived MSCs
      originated metastatic osteoblastic osteosarcoma (OS). To assess the contribution
      of bone environment factors to OS development, we analyzed the effect of the
      osteoinductive factor bone morphogenetic protein-2 (BMP-2) and calcified
      substrates on p53(-/-)RB(-/-) MSCs. We show that BMP-2 upregulates the expression
      of osteogenic markers in a WNT signaling-dependent manner. In addition, the s.c.
      coinfusion of p53(-/-)RB(-/-) MSCs together with BMP-2 resulted in appearance of
      tumoral osteoid areas. Likewise, when p53(-/-)RB(-/-) MSCs were inoculated
      embedded in a calcified ceramic scaffold composed of hydroxyapatite and
      tricalciumphosphate (HA/TCP), tumoral bone formation was observed in the
      surroundings of the HA/TCP scaffold. Moreover, the addition of BMP-2 to the
      ceramic/MSC implants further increased the tumoral osteoid matrix. Together,
      these data indicate that bone microenvironment signals are essential to drive OS
      development.

PMID- 24446213
TI  - 2013: that was the year that was.
AB  - In caring for older people, geriatricians have always adopted a multi-domain
      approach, and this article reflects on the diverse aspects covered by journals in
      general medicine, geriatric medicine and gerontology in 2013. Topics were
      selected that represented developing or controversial areas that are important to
      care of increasingly frail older people. These include the increasing use of
      single physical performance measures in assessment, optimal body mass index,
      assessment of frailty and sarcopenia, dementia, diabetes treatment goals, end-of
      life care, management of complexity and design of health and social services to
      meet complexity. The increasingly important role of patient and carer engagement
      in management of disease and syndromes is highlighted. In particular, two
      eloquent articles from prominent physicians who have been experiencing the ageing
      process and demands of being a dementia carer provide a timely reminder of what
      the reality is in grappling with the inexorable decline that occurs with ageing,
      and caregiving as the central core to what medicine is all about. Looking towards
      the future, the potential of robotic technology, modifying the physical and
      social living environment in improving quality of care and quality of life is
      described.

PMID- 24446211
TI  - Three-dimensional through-time radial GRAPPA for renal MR angiography.
AB  - PURPOSE: To achieve high temporal and spatial resolution for contrast-enhanced
      time-resolved MR angiography exams (trMRAs), fast imaging techniques such as non
      Cartesian parallel imaging must be used. In this study, the three-dimensional
      (3D) through-time radial generalized autocalibrating partially parallel
      acquisition (GRAPPA) method is used to reconstruct highly accelerated stack-of
      stars data for time-resolved renal MRAs. MATERIALS AND METHODS: Through-time
      radial GRAPPA has been recently introduced as a method for non-Cartesian GRAPPA
      weight calibration, and a similar concept can also be used in 3D acquisitions. By
      combining different sources of calibration information, acquisition time can be
      reduced. Here, different GRAPPA weight calibration schemes are explored in
      simulation, and the results are applied to reconstruct undersampled stack-of
      stars data. RESULTS: Simulations demonstrate that an accurate and efficient
      approach to 3D calibration is to combine a small number of central partitions
      with as many temporal repetitions as exam time permits. These findings were used
      to reconstruct renal trMRA data with an in-plane acceleration factor as high as
      12.6 with respect to the Nyquist sampling criterion, where the lowest root mean
      squared error value of 16.4% was achieved when using a calibration scheme with 8
      partitions, 16 repetitions, and a 4 projection * 8 read point segment size.
      CONCLUSION: 3D through-time radial GRAPPA can be used to successfully reconstruct
      highly accelerated non-Cartesian data. By using in-plane radial undersampling, a
      trMRA can be acquired with a temporal footprint less than 4s/frame with a spatial
      resolution of approximately 1.5 mm * 1.5 mm * 3 mm.

PMID- 24446214
TI  - Measuring and defining orthostatic hypotension in the older person.

PMID- 24446215
TI  - Faculty development for hospitalists: structured peer observation of teaching.
AB  - BACKGROUND: Hospitalists provide much of the clinical teaching in internal
      medicine, yet formative feedback to improve their teaching is rare. METHODS: We
      developed a peer observation, assessment, and feedback program to improve
      attending hospitalist teaching. Participants were trained to identify 10 optimal
      teaching behaviors using a structured observation tool that was developed from
      the validated Stanford Faculty Development Program clinical teaching framework.
      Participants joined year-long feedback dyads and engaged in peer observation and
      feedback on teaching. Pre- and post-program surveys assessed confidence in
      teaching, performance of teaching behaviors, confidence in giving and receiving
      feedback, attitudes toward peer observation, and overall satisfaction with the
      program. RESULTS: Twenty-two attending hospitalists participated, averaging 2.2
      years (+/- 2.1 years standard deviation [SD]) experience; 15 (68%) completed pre-
      and post-program surveys. Confidence in giving feedback, receiving feedback, and
      teaching efficacy increased (1 = strongly disagree, 5 = strongly agree, mean +/-
      SD): "I can accurately assess my colleagues' teaching skills," (pre = 3.2 +/- 0.9
      vs post = 4.1 +/- 0.6, P < 0.01), "I can give accurate feedback to my colleagues"
      (pre = 3.4 +/- 0.6 vs post = 4.2 +/- 0.6, P < 0.01), and "I am confident in my
      ability to teach students and residents" (pre = 3.2 +/- 0.9 vs post = 3.7 +/-
      0.8, P = 0.026). CONCLUSIONS: Peer observation and feedback of teaching increases
      hospitalist confidence in several domains that are essential for optimizing
      teaching. Further studies are needed to examine if educational outcomes are
      improved by this program.

PMID- 24446216
TI  - A randomized and controlled multicenter prospective study of the Chinese
      medicinal compound Fufang Xuelian Burn Ointment for the treatment of superficial
      and deep second-degree burn wounds.
AB  - The objective of this study was to evaluate the efficacy and safety of a
      traditional Chinese medicine, Fufang Xuelian Burn Ointment (FXBO), to treat
      superficial and deep second-degree burn wounds. A four-center, randomized,
      controlled, and prospective study was conducted. Overall, 240 patients with
      either superficial or deep second-degree burn wounds were enrolled consecutively
      in this study. Patients who were randomly assigned to the control group
      (superficial: 72, deep: 48) underwent common burn wound therapy, whereas those
      randomized to the treatment group (superficial: 72, deep: 48) received common
      burn wound therapy plus topical FXBO. The healing rate, healing time, effective
      rate, and safety data were compared between the two groups. The baseline
      characteristics were comparable for the two groups. The healing rate was 94.79(+/
      7.50) in the control group and 98.60(+/-5.69) in the FXBO group after 14 days for
      patients with superficial second-degree burn wounds (P = 0.000), and 95.17(+/
      9.68) versus 97.44(+/-9.81) at 28 for deep second-degree burn wounds (P = 0.025).
      The median healing time in the FXBO group were 9 and 21 days for superficial and
      deep second-degree burns, respectively, compared to 10.5 and 22.5 days,
      respectively, in control group (P(superficial) = 0.000 and P(deep) = 0.009). The
      results of the effective rate showed that comprehensive efficacy of the FXBO
      group was improved compared to the control group for either superficial or deep
      second-degree burns (P(superficial) = 0.035 and P deep = 0.003). There were no
      reported drug-related adverse events in both groups. Therefore, FXBO was well
      tolerated and more effective than control group for treating superficial and deep
      second-degree burn wounds.

PMID- 24446217
TI  - Enzymatic and regulatory attributes of trehalose-6-phosphate phosphatase from
      Candida utilis and its role during thermal stress.
AB  - Trehalose-6-phosphate phosphatase (TPP) catalyzes the final step in the
      biosynthesis of the anti-stress sugar trehalose. An 82 kDa TPP enzyme was
      isolated from Candida utilis with 61% yield and 43-fold purification. The protein
      sequence, determined by N-terminal sequencing and MALDI-TOF analysis, showed
      significant homology with known TPP sequences from related organisms. The full
      length gene sequence of TPP of C. utilis was identified using rapid amplification
      of cDNA ends-PCR reaction (RACE-PCR). The gene was cloned and expressed in
      Escherichia coli BL21. Recombinant TPP enzyme was isolated using affinity
      chromatography. CD spectroscopy and steady-state fluorescence revealed that the
      structural and conformational aspects were identical in both native and
      recombinant forms. The biochemical properties of the two forms were also similar.
      Km was determined to be ~0.8 mM. Optimum temperature and pH were found to be 30 
      degrees C and 8.5, respectively. Activity was dependent on the presence of
      divalent cations and inhibited by metal chelators. Methylation-mediated
      regulation of TPP enzyme and its effect on the overall survival of the organism
      under stress were investigated. The results indicated that enhancement of TPP
      activity by methylation at the Cysteine residues increased resistance of Candida
      cells against thermal stress. This work involves extensive investigations toward
      understanding the physico-chemical properties of the first TPP enzyme from any
      yeast strain. The mechanism by which methylation regulates its activity has also
      been studied. A correlation between regulation of trehalose synthesis and
      survivability of the organism under thermal stress was established.

PMID- 24446219
TI  - [The Journal of Psychiatry. A makeover].

PMID- 24446220
TI  - [Outsider].

PMID- 24446218
TI  - Time lapse microscopy observation of cellular structural changes and image
      analysis of drug treated cancer cells to characterize the cellular heterogeneity.
AB  - The effect of Calotropis gigantea latex (CGLX) on human mammary carcinoma cells
      is not well established. We present the results of this drug activity at total
      population and single cell level. CGLX inhibited the growth of MCF7 cancer cells
      at lower IC50 concentration (17 uL/mL). Microscopy of IC50 drug treated cells at
      24 hr confirming the appearance of morphological characteristics of apoptotic and
      necrotic cells, associated with 70% of DNA damage. FACS analysis confirmed that,
      10 and 20% of the disruption of cellular mitochondrial nature by at 24 and 48 h,
      respectively. Microscopic image analysis of total population level proved that
      MMP changes were statistically significant with P values. The cell to cell
      variation was confirmed by functional heterogeneity analysis which proves that
      CGLX was able to induce the apoptosis without the contribution of mitochondria.
      We conclude that CGLX inhibits cell proliferation, survival, and heterogeneity of
      pathways in human mammary carcinoma cells.

PMID- 24446221
TI  - [Farewell].

PMID- 24446222
TI  - [Prevalence, persistency and consequences of ADHD in the Dutch adult population].
AB  - BACKGROUND: Little is known about the prevalence and the consequences of
      attention-deficit hyperactivity disorder (ADHD) among adults in the general Dutch
      population. AIM: To ascertain the prevalence of ADHD in childhood and adulthood,
      to investigate characteristics associated with the prevalence and persistency of
      ADHD and to draw a number of comparisons: to compare the functioning of adults
      with ADHD with that of people with a different mental disorder and to compare the
      extent to which these groups make use of treatment facilities. METHOD: Data were
      derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS
      2), in which the occurrence of ADHD was determined in a representative sample of
      the Dutch population (n = 3,309; aged 18-44). RESULTS: 2.9% of the respondents
      had had ADHD in childhood, 70.0% of them still had the disorder in adulthood. An
      anxiety disorder before the age of 16 increased the risk of ADHD persistency,
      whereas an impulse-control disorder decreased this risk. ADHD in adulthood was
      associated with lower socio-economic status, mental disorders, poor functioning
      and increased use of treatment facilities. ADHD adults and adults with an anxiety
      or substance use disorder showed very similar functional limitations and used
      treatment facilities to approximately the same extent. CONCLUSION: More than two
      thirds of the adults who had had childhood ADHD still had the disorder in
      adulthood. The consequences of this in terms of functioning and use of treatment
      facilities are substantial.

PMID- 24446223
TI  - [ADHD in adults as severe as an anxiety or substance use disorder].

PMID- 24446224
TI  - [The Leiden Routine Outcome Monitoring Study: mood, anxiety and somatoform
      disorders in patients attending a day clinic].
AB  - BACKGROUND: Routine outcome monitoring (rom) is a method for the systematic
      monitoring of treatment-progression. Because rom data are collected regularly and
      systematically, we believe it should be possible to use these data in clinical
      epidemiological research. AIM: To describe, on the basis of publications of the
      Leiden Routine Outcome Monitoring Study, a number of potential research topics in
      which rom data can play a role. METHOD: We used rom data of patients referred,
      between 2004 and 2009, to secondary or tertiary care for treatment of a mood,
      anxiety or somatoform disorder. RESULTS: We describe three cross-sectional
      studies and one prospective study in which we aimed to identify predictors of
      outcome. CONCLUSION: These studies demonstrate clearly that it is feasible to use
      rom data to supplement clinical epidemiological research done on patients.
      Together these findings can be a useful addition to data derived from randomised
      clinical trials.

PMID- 24446225
TI  - [Substance use and criminality: a review].
AB  - BACKGROUND: Substance use regularly co-occurs with many types of criminality,
      including violent behaviour. AIM: To review the relationships between substance
      abuse and criminality, which can involve violent behaviour. METHOD: We searched
      the literature for meta-analyses, reviews and empirical articles about
      relationships between the problematic use of and addiction to psychoactive
      substances on the one hand and antisocial and aggressive behaviour and recidivism
      on the other hand. RESULTS: In the case of both men and women there are
      significant relationships between substance abuse and criminal behavior. The
      majority of substance users, however, are not criminals and most of the offences
      they commit can be termed 'acquisitive offences'. The relationship between
      alcohol and violence is stronger than the relationship between substance abuse
      and violence. Furthermore, it is only in cocaine users that we find indications
      that psychopharmacological effects stimulate violent behaviour. A number of
      factors, particularly interactions, determine whether substance abusers are
      criminal and are violent. Violent behaviour can result from interactions between
      the severity of illness caused by substance abuse, individual psychological,
      social and neurobiological characteristics, situational factors and expectancies
      regarding the psychopharmacological effects of a particular substance.
      CONCLUSION: Substance abuse, particularly the combination of alcohol and drugs,
      is a predictor of criminality and criminal recidivism.

PMID- 24446226
TI  - [Social dysfunction of young persons with an ultra high risk of developing first
      episode psychosis].
AB  - BACKGROUND: Schizophrenia is associated with severe social deficits. Social
      dysfunction is common in young persons with an ultra high risk (UHR) of
      developing a psychotic disorder. AIM: To present an overview of the literature on
      social deficits in the uhr phase, and to find out what role these deficits play
      in the prediction of a first psychotic episode. METHOD: We searched the
      literature using Psycinfo (covering the period from 1995 to January 2013) in
      order to locate articles relating to the role of social dysfunction in the UHR
      phase. RESULTS: Young persons who meet one or more UHR criteria face more social
      constraints than the general population. Effect-sizes indicate differences
      ranging from medium to substantial (range Cohen's d = .63 - 4.18). Impairments in
      both social and role functioning contribute to the prediction of a first
      psychotic episode in UHR young persons. CONCLUSION: Research conducted on UHR
      adolescents shows, without exception, that functional limitations are already
      manifest in the phase preceding a clinical psychotic disorder. The experiencing
      of UHR symptoms is itself associated with (severe) social deficits that require
      treatment, regardless of whether the help-seeking uhr individual eventually
      develops a psychosis.

PMID- 24446227
TI  - [Hidden diseases: tuberculosis in a woman with a severe mental illness].
AB  - Patients with severe mental illness often have only limited access to health care
      for physical symptoms. They have difficulty in organising their thoughts and
      articulating their requests for medical help; in addition, they often have a
      reduced perception of stimuli like physical pain. There may also be a language
      barrier and sometimes a cultural barrier. The case that we present demonstrates
      that these are not separate causes but they are interrelated in a complex manner.
      Screening for a latent disease such as tuberculosis reduces the risk of a delayed
      diagnosis stemming from the patient's inability to articulate a request for
      medical help. The physical symptoms of patients with severe mental illness can
      only be reliably interpreted when there is close cooperation between physicians
      and psychiatrists.

PMID- 24446228
TI  - [Body integrity identity disorder, relief after amputation].
AB  - Body integrity identity disorder (BIID) is a rare condition in which a person,
      for no apparent physical reason, is tormented by the experience that a body-part,
      such as a limb, does not really belong to the body. Patients experience an
      intense desire for the limb to be amputated (a 'desire' formerly referred to as
      'apotemnophilia'). We report on a 58-year-old male patient with BIID who froze
      one of his legs so that he could amputate it himself. A surgeon ultimately
      intervened and amputated the leg professionally. The patient was extremely
      relieved and was still experiencing relief at a follow-up three years later.

PMID- 24446229
TI  - Palmitic acid affects proliferation and differentiation of neural stem cells in
      vitro.
AB  - High-lipid diet composed of saturated fatty acids (SFAs) has significant
      detrimental effects on brain homeostasis, and deleterious effects of SFAs on
      various cells have been well documented. However, the effects of SFAs on neural
      stem Cells (NSCs) function have not been fully explored. The aim of this study
      was to determine whether palmitic acid (PA) affected the proliferation and
      differentiation of murine-derived NSCs. The results showed that PA dose
      dependently suppressed viability of NSCs and was cytotoxic at high
      concentrations. The toxic levels of PA inhibited the proliferation of NSCs as
      shown by reduced bromodeoxyuridine labeling of NSCs, which is correlated with
      reactive oxygen species generation. Pretreatment of the cells with the
      antioxidant N-acetyl-L-cysteine inhibitor significantly attenuated the effects of
      PA on the proliferation of NSCs. Furthermore, nontoxic levels of PA promoted
      astrocytogenesis in the differentiated NSCs, associated with Stat3 activation and
      altered expression of serial of basic helix-loop-helix transcription factor
      genes. Altogether, our data have demonstrated that PA has a significant impact on
      proliferation and differentiation of NSCs in vitro and may be useful for
      elucidating the role of SFAs in regulating NSCs fate in physiological and
      pathological settings.

PMID- 24446230
TI  - Does MRI breast "density" (degree of background enhancement) correlate with
      mammographic breast density?
AB  - PURPOSE: To investigate whether mammographic breast densities and the respective
      degree of MRI background enhancement would correlate. Mammographic breast density
      is coded to communicate how likely a cancer is obscured by parenchyma. Similarly,
      background enhancement in breast MRI could obscure enhancing cancer tissue.
      MATERIALS AND METHODS: A total of 468 women underwent standard full-field digital
      mammography and dynamic contrast-enhanced breast MRI in our institution.
      Mammographic breast density was scored according to the American College of
      Radiology-classification; background enhancement in MRI was scored on a 4-point
      scale from absent to severe. Breast "density classes" were retrospectively
      compared by analyzing the differences between scores for mammography and MRI.
      Statistical correlation was calculated using the Spearman coefficient. RESULTS:
      Scores matched in 19% of women (90/468) but differed in 81% (378/468). A
      deviation by 1 point was observed in 33% (157/468), by 2 points in 38% (179/468),
      by 3 in 9% (42/468). Scores for background enhancement were lower than
      mammographic scores in 371/468 (79.3%), equivalent in 90/468 (19.2%), and higher
      in 7/468 (1.5%). CONCLUSION: Mammographic breast density does not correlate with
      the degree of background enhancement in MRI. In the majority of women, scores for
      background enhancement in MRI will be lower than the respective mammographic
      density scores.

PMID- 24446231
TI  - Apolipoproteins E and J interfere with amyloid-beta uptake by primary human
      astrocytes and microglia in vitro.
AB  - Defective clearance of the amyloid-beta peptide (Abeta) from the brain is
      considered a strong promoter in Alzheimer's disease (AD) pathogenesis. Astrocytes
      and microglia are important mediators of Abeta clearance and Abeta aggregation
      state and the presence of amyloid associated proteins (AAPs), such as
      Apolipoproteins E and J (ApoE and ApoJ), may influence Abeta clearance by these
      cells. Here we set out to investigate whether astrocytes and microglia differ in
      uptake efficiency of Abeta oligomers (Abetaoligo ) and Abeta fibrils (Abetafib ),
      and whether the Abeta aggregation state and/or presence of AAPs affect Abeta
      uptake in these cells in vitro. Adult human primary microglia and astrocytes,
      isolated from short delay post-mortem brain tissue, were exposed to either
      Abetaoligo or Abetafib alone or combined with a panel of certain AAPs whereafter
      Abeta-positive cells were quantified using flow cytometry. Upon exposure to Abeta
      combined with ApoE, ApoJ, alpha1-antichymotrypsin (ACT) and a combination of
      serum amyloid P and complement C1q (SAP-C1q), a clear reduction in astrocytic but
      not microglial Abetaoligo uptake, was observed. In contrast, Abetafib uptake was
      strongly reduced in the presence of AAPs in microglia, but not in astrocytes.
      These data provide the first evidence of distinct roles of microglia and
      astrocytes in Abeta clearance. More importantly we show that Abeta clearance by
      glial cells is negatively affected by AAPs like ApoE and ApoJ. Thus, targeting
      the association of Abeta with AAPs, such as ApoE and ApoJ, could serve as a
      therapeutic strategy to increase Abeta clearance by glial cells.

PMID- 24446232
TI  - Discharge before noon: an achievable hospital goal.
AB  - BACKGROUND: Late afternoon hospital discharges are thought to contribute to
      admission bottlenecks, overcrowding, and increased length of stay (LOS). In
      January 2012, the discharge before noon (DBN) percentage on 2 medical units was
      7%, below the organizational goal of 30%. OBJECTIVE: To sustainably achieve a DBN
      rate of 30% and to evaluate the effect of this intervention on observed-to
      expected (O/E) LOS and 30-day readmission rate. DESIGN: Pre-/post-intervention
      retrospective analysis. SETTING: Two acute care inpatient medical units in an
      urban, academic medical center. PATIENTS: All inpatients discharged from the
      units. INTERVENTION: All staff helped create a checklist of daily
      responsibilities at a DBN kickoff event. We initiated afternoon interdisciplinary
      rounds to identify next-day DBNs and created a website for enhanced
      communication. We provided daily feedback on the DBN percentage, rewards for
      success, and real-time opportunities for case review. MEASUREMENTS: Calendar
      month DBN percentage, O/E LOS, and 30-day readmission rate. RESULTS: The DBN
      percentage increased from 11% in the 8-month baseline period to an average of 38%
      over the 13-month intervention (P = 0.0002). The average discharge time moved 1
      hour and 31 minutes earlier in the day. The O/E LOS declined from 1.06 to 0.96 (P
      = 0.0001), and the 30-day readmission rate declined from 14.3% to 13.1% (P =
      0.1902). CONCLUSIONS: Our study demonstrates that increased DBN is an achievable
      and sustainable goal for hospitals. Future work will allow for better
      understanding of the full effects of such an intervention on patient outcomes and
      hospital metrics.

PMID- 24446233
TI  - Outcome-related co-factors in 105 cases of vertebral osteomyelitis in a tertiary
      care hospital.
AB  - PURPOSE: Vertebral osteomyelitis (VO) is an infection of the vertebral body and
      the adjacent disc space. The aim of our study was to identify outcome-related co
      factors of patients with VO treated in the last decade. METHODS AND RESULTS: We
      retrospectively identified 105 patients with VO (mean age 66.1 years) who had
      been treated at our institution from 2004 to 2011. The median time of
      hospitalization at our institution was 31.5 days, and 44 patients required
      intensive medical care. Back pain and fever were documented in 66.7 and 33.3 % of
      cases, respectively. The radiologic diagnosis of VO was made in 94.8 % of all
      obtained magnetic resonance imaging scans and in 66.2 % of all computed
      tomography (CT) scans. Biopsies were taken in 71 patients, and the causative
      organisms were identified in 56.2 % of patients, with Staphylococcus aureus being
      the predominant pathogen. Fifty-six patients underwent surgical treatment. During
      hospitalization, infectious complications were observed in 63 patients (60.0 %).
      The most common complications were psoas, paravertebral and epidural abscesses.
      Patients with S. aureus infections had a significantly higher rate of infectious
      complications than those without (76.5 vs. 40.3 %, respectively), and were more
      frequently treated in intensive care units (58.8 vs. 34.7 %, respectively).
      Overall in-hospital mortality rate was 12.4 %. Elevated C-reactive protein levels
      at admission, advanced age and a Charlson Comorbidity Index of >=2 were
      associated with higher mortality. CONCLUSIONS: Magnetic resonance imaging
      currently is the imaging procedure of choice for the radiologic diagnosis of VO.
      Mortality is attributable in part to co-morbidities. However, infections with S.
      aureus are frequent in this patient population and are associated with a higher
      rate of complications and a trend towards higher mortality.

PMID- 24446235
TI  - The existence of hexafluoroarsenic(V) acid.
AB  - The homogeneous mixture of anhydrous hydrogen fluoride aHF and antimony
      pentafluoride AsF5 is known as a superacidic system. The high acidity is derived
      from the formation of [H2F](+) [AsF6](-). No experimental evidence exists for the
      existence of the free acid molecule HAsF6. The reaction of trimethylsilyl N,N
      dimethylcarbamate in the binary system aHF/AsF5 led to decomposition of
      trimethylsilyl N,N-dimethylcarbamate at -50  degrees C to dimethylammonium
      hexafluoridoarsenate and cocrystallization of HAsF6. The single-crystal X-ray
      structure displays an HAsF6 molecule involved in an asymmetric hydrogen bridge to
      the hexafluoridoarsenate anion. As a result of the incalculable situation in the
      crystal lattice, the molecular structure of HAsF6 is calculated by quantum
      chemical structure optimization of the extreme cases of [FHF-AsF5](-) (strong
      hydrogen bond) and HAsF6 (no hydrogen bond) at the PBE1PBE/6-311G(3df,3pd) level
      of theory.

PMID- 24446234
TI  - Structure-based neuron retrieval across Drosophila brains.
AB  - Comparing local neural structures across large sets of examples is crucial when
      studying gene functions, and their effect in the Drosophila brain. The current
      practice of aligning brain volume data to a joint reference frame is based on the
      neuropil. However, even after alignment neurons exhibit residual location and
      shape variability that, together with image noise, hamper direct quantitative
      comparison and retrieval of similar structures on an intensity basis. In this
      paper, we propose and evaluate an image-based retrieval method for neurons,
      relying on local appearance, which can cope with spatial variability across the
      population. For an object of interest marked in a query case, the method ranks
      cases drawn from a large data set based on local neuron appearance in confocal
      microscopy data. The approach is based on capturing the orientation of neurons
      based on structure tensors and expanding this field via Gradient Vector Flow.
      During retrieval, the algorithm compares fields across cases, and calculates a
      corresponding ranking of most similar cases with regard to the local structure of
      interest. Experimental results demonstrate that the similarity measure and
      ranking mechanisms yield high precision and recall in realistic search scenarios.

PMID- 24446237
TI  - Retinal injury by industrial laser burn.
AB  - The following case study describes an injury sustained to the fovea of the right
      eye of a senior en gineer engaged in the repair of a neodymium-doped yttrium
      aluminium garnet (Nd:YAG) laser. Our patient presented with sudden loss of vision
      in his right eye following accidental exposure to an intense beam of light after
      the laser's xenon flash-lamp fired unexpectedly. This accident occurred while the
      patient was aligning the optical coupler mirror parallel to Nd:YAG laser rod ends
      using an L-CAT alignment aid. We describe the mechanism of retinal injury,
      outcome and important issues regarding the safe use of lasers. 

PMID- 24446238
TI  - Ventilator Settings Can Substantially Impact Patients' Comfort.
AB  - BACKGROUND: With increasing realization that sedatives may complicate care of
      mechanically ventilated patients, greater emphasis might turn to promoting
      comfort by titration of ventilator settings. HYPOTHESIS: Patients with acute on
      chronic respiratory failure (ACRF) with underlying chronic obstructive pulmonary
      disease (COPD) demonstrate different levels of comfort in response to varying
      ventilator settings compared to those with underlying obesity hypoventilation
      syndrome (OHS). METHODS: Patients recovering from ACRF with underlying COPD or
      OHS were randomized to varying combinations of ventilator modes (assist control
      and pressure support), tidal volumes, and inspiratory flows for 3
      minutes/setting. For each ventilator setting, physiologic variables were recorded
      and patients indicated their level of comfort using a 10-point Borg scale.
      RESULTS: In all, 20 patients, aged 68 +/- 13 years (standard deviation) and
      ventilated for 4.9 days, were enrolled. Of 20 patients, 13 had COPD and 7 had
      OHS. No ventilator mode, flow, or tidal volume provided consistently greater
      comfort between the groups, but patients reported substantial ranges of comfort
      (up to 8 Borg points) across the ventilator settings studied. There were no
      significant differences in heart rate, blood pressure, or airway pressures within
      patients across ventilator settings or between the groups, but patients with OHS
      were more tachypneic compared to patients with COPD while breathing on assist
      control of 6 mL/kg (constant flow 60 L/min) and 8 mL/kg (decelerating flow 40
      L/min). There was no correlation between comfort and systolic blood pressure,
      heart rate, or respiratory rate. CONCLUSION: Ventilator parameters may impact
      patients' comfort substantially. Future studies may help identify evidence-based
      methodology for gauging comfort following changes in ventilator settings and the
      settings that are most likely to positively impact various groups of patients.

PMID- 24446239
TI  - Functional role of connexins and pannexins in the interaction between vascular
      and nervous system.
AB  - The microvascular network of the microcirculation works in tight communication
      with surrounding tissues to control blood supply and exchange of solutes. In
      cerebral circulation, microvascular endothelial cells constitute a selective
      permeability barrier that controls the environment of parenchymal brain tissue,
      which is known as the blood-brain barrier (BBB). Connexin- and pannexin-formed
      channels (gap junctions and hemichannels) play a central role in the coordination
      of endothelial and smooth muscle cell function and connexin-mediated signaling in
      endothelial cells is essential in the regulation of BBB permeability. Likewise,
      gap junction communication between astrocyte end-feet also contributes to
      maintain the BBB integrity, but the participation of hemichannels in this process
      cannot be discarded. Sympathetic and sensory perivascular nerves are also
      involved in the control and coordination of vascular function through the release
      of vasoconstrictor or vasodilator signals and by the regulation of gap junction
      communication in the vessel wall. Conversely, ATP release through pannexin-1
      formed channels mediates the alpha1-adrenergic signaling. Furthermore, here we
      show that capsaicin-induced CGRP release from mesenteric perivascular sensory
      nerves induces pannexin-1-formed channel opening, which in turn leads to
      reduction of pannexin-1 and endothelial nitric oxide synthase (eNOS) expression
      along the time. Interestingly, blockade of CGRP receptors with CGRP8-37 increased
      eNOS expression by ~5-fold, suggesting that capsaicin-sensitive sensory nerves
      are involved in the control of key signaling proteins for vascular function. In
      this review, we discuss the importance of connexin-based channels in the control
      of BBB integrity and the functional interaction of vascular connexins and
      pannexins with the peripheral nervous system.

PMID- 24446236
TI  - Tracking the elusive fibrocyte: identification and characterization of collagen
      producing hematopoietic lineage cells during murine wound healing.
AB  - Fibrocytes are a unique population of circulating cells reported to exhibit
      characteristics of both hematopoietic and mesenchymal cells, and play an
      important role in wound healing. However, putative fibrocytes have been found to
      lose expression of hematopoietic surface markers such as CD45 during
      differentiation, making it difficult to track these cells in vivo with
      conventional methodologies. In this study, to distinguish hematopoietic and
      nonhematopoietic cells without surface markers, we took advantage of the gene vav
      1, which is expressed solely on hematopoietic cells but not on other cell types,
      and established a novel transgenic mouse, in which hematopoietic cells are
      irreversibly labeled with green fluorescent protein and nonhematopoietic cells
      with red fluorescent protein. Use of single-cell transcriptional analysis in this
      mouse model revealed two discrete types of collagen I (Col I) expressing cells of
      hematopoietic lineage recruited into excisional skin wounds. We confirmed this
      finding on a protein level, with one subset of these Col I synthesizing cells
      being CD45+ and CD11b+, consistent with the traditional definition of a
      fibrocyte, while another was CD45- and Cd11b-, representing a previously
      unidentified population. Both cell types were found to initially peak, then
      reduce posthealing, consistent with a disappearance from the wound site and not a
      loss of identifying surface marker expression. Taken together, we have
      unambiguously identified two cells of hematopoietic origin that are recruited to
      the wound site and deposit collagen, definitively confirming the existence and
      natural time course of fibrocytes in cutaneous healing.

PMID- 24446240
TI  - Implementation of a quality improvement initiative in Belgian diabetic foot
      clinics: feasibility and initial results.
AB  - BACKGROUND: This article aims to describe the implementation and initial results
      of an audit-feedback quality improvement initiative in Belgian diabetic foot
      clinics. METHODS: Using self-developed software and questionnaires, diabetic foot
      clinics collected data in 2005, 2008 and 2011, covering characteristics, history
      and ulcer severity, management and outcome of the first 52 patients presenting
      with a Wagner grade >= 2 diabetic foot ulcer or acute neuropathic
      osteoarthropathy that year. Quality improvement was encouraged by meetings and by
      anonymous benchmarking of diabetic foot clinics. RESULTS: The first audit
      feedback cycle was a pilot study. Subsequent audits, with a modified methodology,
      had increasing rates of participation and data completeness. Over 85% of diabetic
      foot clinics participated and 3372 unique patients were sampled between 2005 and
      2011 (3312 with a diabetic foot ulcer and 111 with acute neuropathic
      osteoarthropathy). Median age was 70 years, median diabetes duration was 14 years
      and 64% were men. Of all diabetic foot ulcers, 51% were plantar and 29% were both
      ischaemic and deeply infected. Ulcer healing rate at 6 months significantly
      increased from 49% to 54% between 2008 and 2011. Management of diabetic foot
      ulcers varied between diabetic foot clinics: 88% of plantar mid-foot ulcers were
      off-loaded (P10-P90: 64-100%), and 42% of ischaemic limbs were revascularized
      (P10-P90: 22-69%) in 2011. CONCLUSIONS: A unique, nationwide quality improvement
      initiative was established among diabetic foot clinics, covering ulcer healing,
      lower limb amputation and many other aspects of diabetic foot care. Data
      completeness increased, thanks in part to questionnaire revision. Benchmarking
      remains challenging, given the many possible indicators and limited sample size.
      The optimized questionnaire allows future quality of care monitoring in diabetic
      foot clinics.

PMID- 24446241
TI  - Nonredundant function of two highly homologous octopamine receptors in food
      deprivation-mediated signaling in Caenorhabditis elegans.
AB  - It is common for neurotransmitters to possess multiple receptors that couple to
      the same intracellular signaling molecules. This study analyzes two highly
      homologous G-protein-coupled octopamine receptors using the model animal
      Caenorhabditis elegans. In C. elegans, the amine neurotransmitter octopamine
      induces activation of cAMP response element-binding protein (CREB) in the
      cholinergic SIA neurons in the absence of food through activation of the Gq
      coupled octopamine receptor SER-3 in these neurons. We also analyzed another Gq
      coupled octopamine receptor, SER-6, that is highly homologous to SER-3. As seen
      in ser-3 deletion mutants, octopamine- and food-deprivation-mediated CREB
      activation was decreased in ser-6 deletion mutants compared with wild-type
      animals, suggesting that both SER-3 and SER-6 are required for signal
      transduction. Cell-specific expression of SER-6 in the SIA neurons was sufficient
      to restore CREB activation in the ser-6 mutants, indicating that SER-6, like SER
      3, functions in these neurons. Taken together, these results demonstrate that two
      similar G-protein-coupled receptors, SER-3 and SER-6, function in the same cells
      in a nonredundant manner.

PMID- 24446242
TI  - Elevation in multiple serum inflammatory biomarkers predicts survival of
      pancreatic cancer patients with inoperable disease.
AB  - PURPOSE: Cancer-associated inflammation plays a driver role in pancreatic tumor
      development and progression. Moreover, recent studies have implicated the
      inflammatory tumor microenvironment in modulating therapy response and inducing
      resistance. The aim of this study is to investigate the prognostic and predictive
      value of the inflammatory biomarkers serum ferritin and C-reactive protein (CRP)
      in advanced pancreatic cancer patients. METHODS: We measured pretreatment serum
      ferritin and CRP levels in 159 patients with inoperable pancreatic cancer
      participating in a phase III trial. RESULTS: Serum ferritin and CRP levels were
      examined for correlations with overall survival using Kaplan-Meier analysis. When
      analyzed on a categorical basis, patients with higher ferritin (>median) or CRP
      (>25th percentile) had shorter overall survival. Moreover, the two biomarkers
      were not correlated suggesting independent mechanisms of production and release.
      However, when patients were evaluated by their ferritin and CRP levels, only
      patients with elevation in both inflammatory biomarkers showed a significant
      decrease in overall survival. CONCLUSIONS: Serum ferritin and CRP are independent
      prognostic factors for shorter survival in patients with inoperable pancreatic
      tumors. Moreover, the evaluation of patients based on both biomarkers suggested
      that their prognostic value, although independent, reflected the broader state of
      cancer-associated inflammation. Thus, serum ferritin and CRP should be further
      explored as clinical biomarkers.

PMID- 24446243
TI  - Mitochondrial but not plasmalemmal BK channels are hypoxia-sensitive in human
      glioma.
AB  - Tumor cells are resistant to hypoxia but the underlying mechanism(s) of this
      tolerance remain poorly understood. In healthy brain cells, plasmalemmal Ca(2+)
      activated K(+) channels ((plasma)BK) function as oxygen sensors and close under
      hypoxic conditions. Similarly, BK channels in the mitochondrial inner membrane
      ((mito)BK) are also hypoxia sensitive and regulate reactive oxygen species
      production and also permeability transition pore formation. Both channel
      populations are therefore well situated to mediate cellular responses to hypoxia.
      In tumors, BK channel expression increases with malignancy, suggesting these
      channels contribute to tumor growth; therefore, we hypothesized that the
      sensitivity of (plasma)BK and/or (mito)BK to hypoxia differs between glioma and
      healthy brain cells. To test this, we examined the electrophysiological
      properties of (plasma)BK and (mito)BK from a human glioma cell line during
      normoxia and hypoxia. We observed single channel activities in whole cells and
      isolated mitoplasts with slope conductance of 199 +/- 8 and 278 +/- 10 pA,
      respectively. These currents were Ca(2+)- and voltage-dependent, and were
      inhibited by the BK channel antagonist charybdotoxin (0.1 MUM). (plasma)BK could
      only be activated at membrane potentials >+40 mV and had a low open probability
      (NPo) that was unchanged by hypoxia. Conversely, (mito)BK were active across a
      range of membrane potentials (-40 to +40 mV) and their NPo increased during
      hypoxia. Activating (plasma)BK, but not (mito)BK induced cell death and this
      effect was enhanced during hypoxia. We conclude that unlike in healthy brain
      cells, glioma (mito)BK channels, but not (plasma)BK channels are oxygen
      sensitive.

PMID- 24446244
TI  - Process evaluation of the MOSAIC Trial, Part I: Therapist experiences of
      delivering two psychological therapies for treatment of anorexia nervosa.
AB  - OBJECTIVES: Forming part of a process evaluation of a large randomised controlled
      trial (the Maudsley Outpatient Study of Treatments for Anorexia Nervosa and
      Related conditions, MOSAIC) comparing two outpatient therapies for Anorexia
      Nervosa (AN), the Maudsley Model for Treatment of Adults with Anorexia Nervosa
      (MANTRA) and Specialist Supportive Clinical Management (SSCM), this study adopted
      a qualitative approach to examine therapist experiences of treatment delivery.
      METHOD: Twenty MOSAIC therapists completed semi-structured interviews. Interviews
      were recorded, transcribed and analysed thematically. RESULTS: Themes of positive
      aspects, challenges and therapeutic fit emerged. MANTRA was seen as structured
      and flexible but could feel demanding on therapist time and skill. The slow pace
      and narrower focus of SSCM gave patients space to talk, but the lack of
      psychological tools and nutritional emphasis could create frustration. Views on
      the therapeutic relationship and patient-therapy fit differed across treatments.
      DISCUSSION: Findings provide testable hypotheses about what works for whom, ideas
      for therapist training, treatment development and delivery.

PMID- 24446245
TI  - Single-layered ultrasmall nanoplates of MoS2 embedded in carbon nanofibers with
      excellent electrochemical performance for lithium and sodium storage.
AB  - The preparation and electrochemical storage behavior of MoS2 nanodots--more
      precisely single-layered ultrasmall nanoplates--embedded in carbon nanowires has
      been studied. The preparation is achieved by an electrospinning process that can
      be easily scaled up. The rate performance and cycling stability of both lithium
      and sodium storage were found to be outstanding. The storage behavior is,
      moreover, highly exciting from a fundamental point of view, as the differences
      between the usual storage modes--insertion, conversion, interfacial storage--are
      beneficially blurred. The restriction to ultrasmall reaction domains allows for
      an almost diffusion-less and nucleation-free "conversion", thereby resulting in a
      high capacity and a remarkable cycling performance.

PMID- 24446246
TI  - The effect of polyglycerol sulfate branching on inflammatory processes.
AB  - In this study, the extent to which the scaffold architecture of polyglycerol
      sulfates affects inflammatory processes and hemocompatibility is investigated.
      Competitive L-selectin binding assays, cellular uptake studies, and blood
      compatibility readouts are done to evaluate distinct biological properties. Fully
      glycerol based hyperbranched polyglycerol architectures are obtained by either
      homopolymerization of glycidol (60% branching) or a new copolymerization strategy
      of glycidol with ethoxyethyl glycidyl ether. Two polyglycerols with 24 and 42%
      degree of branching (DB) are synthesized by using different monomer feed ratios.
      A perfectly branched polyglycerol dendrimer is synthesized according to an
      iterative two-step protocol based on allylation of the alcohol and subsequent
      catalytic dihydroxylation. All the polyglycerol sulfates are synthesized with a
      comparable molecular weight and degree of sulfation. The DB make the different
      polymer conjugates perform different ways. The optimal DB is 60% in all
      biological assays. 

PMID- 24446247
TI  - The Puralpha/Purbeta single-strand DNA-binding proteins attenuate smooth-muscle
      actin gene transactivation in myofibroblasts.
AB  - Expression of smooth muscle alpha-actin (SMalphaA) is essential for myofibroblast
      mediated wound contraction following tissue injury. The Pur alpha/beta and YB-1
      transcriptional repressors govern the DNA-binding activity of serum response
      factor (SRF) and phosphorylated Smad3 (pSmad3) transcriptional activators during
      induction of SMalphaA gene expression in human pulmonary myofibroblasts. In
      quiescent fibroblasts, Pur alpha exhibited a novel function in enhancing
      stability of pre-existing SRF complexes with SMalphaA core promoter DNA, whereas
      Pur beta was more effective in disrupting SRF-DNA interaction. Pur proteins were
      less efficient competitors of pre-existing, core-promoter complexes containing
      both SRF and pSmad3 in nuclear extracts from TGFbeta1-activated myofibroblasts.
      TGFbeta1 signaling dissociated a SRF/Pur protein complex with concurrent
      formation of a transient pSmad3/MRTF-A/Pur beta complex during early phase
      myofibroblast differentiation. Pur beta was replaced by Pur alpha in the
      pSmad3/MRTF-A complex in mature myofibroblasts. Combining all three repressors
      potently inhibited SRF and pSmad3 binding to promoter DNA in quiescent
      fibroblasts and TGFbeta1-activated myofibroblasts, respectively. The results
      point to dynamic interplay between transcriptional activators and repressors in
      regulating SMalphaA gene output during myofibroblast differentiation. Therapeutic
      targeting of nucleoprotein complexes regulating the SMalphaA promoter may prevent
      excessive myofibroblast accumulation associated with chronic cardiopulmonary
      fibrosis and dysfunctional tissue remodeling.

PMID- 24446249
TI  - Chemical shift encoding-based water-fat separation methods.
AB  - The suppression of signal from fat constitutes a basic requirement in many
      applications of magnetic resonance imaging. To date, this is predominantly
      achieved during data acquisition, using fat saturation, inversion recovery, or
      water excitation methods. Postponing the separation of signal from water and fat
      until image reconstruction holds the promise of resolving some of the problems
      associated with these methods, such as failure in the presence of field
      inhomogeneities or contrast agents. In this article, methods are reviewed that
      rely on the difference in chemical shift between the hydrogen atoms in water and
      fat to perform such a retrospective separation. The basic principle underlying
      these so-called Dixon methods is introduced, and some fundamental implementations
      of the required chemical shift encoding in the acquisition and the subsequent
      water-fat separation in the reconstruction are described. Practical issues, such
      as the selection of key parameters and the appearance of typical artifacts, are
      illustrated, and a broad range of applications is demonstrated, including
      abdominal, cardiovascular, and musculoskeletal imaging. Finally, advantages and
      disadvantages of these Dixon methods are summarized, and emerging opportunities
      arising from the availability of information on the amount and distribution of
      fat are discussed.

PMID- 24446250
TI  - Establishing a multidisciplinary diabetic foot team in a large tertiary hospital:
      a workshop.
AB  - Every year, over 1 million people with diabetes lose a leg due to diabetic foot
      disease. Most amputations are preceded by a foot ulcer. Causes for the
      development of foot ulcers are generally multifactorial and may include
      neuropathy, peripheral vasculopathy, abnormal foot mechanics and infection.
      Multidisciplinary approach to the patient with acute diabetic foot is mandatory
      and has been shown to reduce amputation rate. In our article we describe the
      establishment of a multidisciplinary diabetic foot team in a large tertiary
      hospital and its outcomes.

PMID- 24446248
TI  - Clinical relevance of brain volume measures in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic disease with an inflammatory and
      neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in
      the disease course and may lead to irreversible neurological impairment. Changes
      in brain volume, observed from the earliest stage of MS and proceeding throughout
      the disease course, may be an accurate measure of neurodegeneration and tissue
      damage. There are a number of magnetic resonance imaging-based methods for
      determining global or regional brain volume, including cross-sectional (e.g.
      brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural
      Image Evaluation using Normalization of Atrophy]). Although these methods are
      sensitive and reproducible, caution must be exercised when interpreting brain
      volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding
      effect on measurements, especially in a disease with complex pathological
      substrates such as MS. Brain volume loss has been correlated with disability
      progression and cognitive impairment in MS, with the loss of grey matter volume
      more closely correlated with clinical measures than loss of white matter volume.
      Preventing brain volume loss may therefore have important clinical implications
      affecting treatment decisions, with several clinical trials now demonstrating an
      effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In
      clinical practice, it may therefore be important to consider the potential impact
      of a therapy on reducing the rate of brain volume loss. This article reviews the
      measurement of brain volume in clinical trials and practice, the effect of DMTs
      on brain volume change across trials and the clinical relevance of brain volume
      loss in MS.

PMID- 24446251
TI  - The benefits of e-health support for older family caregivers in rural areas.
AB  - We conducted a pragmatic, mixed methods study comparing rural family caregivers
      receiving e-health caregiver support (n = 35) with a control group (n = 21)
      receiving conventional, non-e-health, caregiver support. After 18 months, the
      benefits of support were evaluated using the Care Effectiveness Scale (40-items
      exploring the domains of preparedness, enrichment and predictability). In all
      domains the e-health group scored significantly higher than the control group.
      The adjusted difference for overall benefits was 3.0 (P = 0.02) on the scale 0
      10. In addition, semi structured interviews were conducted with a sub-sample of
      the caregivers. For the e-health group flexibility, availability and being able
      to individualise the support were essential factors. All caregivers in the
      control group found conventional support to be beneficial, but also stressed
      unmet needs related to the conventional support being standardised and non
      flexible. The study suggests that providers of caregiver support should offer e
      health support as an alternative to conventional caregiver support, as it can be
      more beneficial to family caregivers. 

PMID- 24446252
TI  - Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression
      in breast cancer patients.
AB  - The goal of this study was to determine the diagnostic and prognostic potential
      of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer. We
      analyzed a tissue microarray comprised of 100 breast cancer cases and 70 matched
      normal samples. Analysis of an online database, which included 2,977 patients,
      was also performed. There was a significant difference in cytoplasmic expression
      of XIAP (XIAP-C) between breast cancer tissue and matched normal (p<0.001).
      Staining of XIAP-C was defined as negative (breast cancer 8.42% vs. normal
      30.91%), slight (40.0 vs. 45.45%), moderate (43.16 vs. 23.64%), or high (8.42 vs.
      0%). High XIAP-C protein expression correlated with human epidermal growth factor
      receptor 2 (HER-2) status (p=0.010) and with human p53 mutant-type (P53) status
      (p=0.039). We found that XIAP expression did not correlate with disease-free
      survival (p=0.706) and overall survival (p=0.496) of breast cancer patients. An
      Internet-based system analysis confirmed our results. In the subgroup analysis,
      basal-like breast cancer patients with high XIAP levels in the tumor had a
      significantly increased risk of relapse; thus, the up-regulation of XIAP appeared
      to be predictive of poor relapse-free survival (p=0.013). Kaplan-Meier curves
      also identified a significant correlation between distant metastasis-free
      survival and XIAP expression in patients with lymph-node-negative disease
      (p=0.030). In summary, expression of XIAP-C was significantly higher in breast
      cancer compared to normal tissue. XIAP-C expression correlated with HER-2 status
      and may be considered a prognostic biomarker for basal-like breast cancer
      patients.

PMID- 24446253
TI  - VHL and HIF-1alpha: gene variations and prognosis in early-stage clear cell renal
      cell carcinoma.
AB  - Von Hipple-Lindau gene (VHL) inactivation represents the most frequent
      abnormality in clear cell renal cell carcinoma (ccRCC). Hypoxia-inducible factor
      1alpha (HIF-1alpha) expression is regulated by O2 level. In normal O2 conditions,
      VHL binds HIF-1alpha and allows HIF-1alpha proteasomal degradation. A single
      nucleotide polymorphism (SNP) has been found located in the oxygen-dependent
      degradation domain at codon 582 (C1772T, rs11549465, Pro582Ser). In hypoxia,
      VHL/HIF-1alpha interaction is abolished and HIF-1alpha activates target genes in
      the nucleus. This study analyzes the impact of genetic alterations and protein
      expression of VHL and the C1772T SNP of HIF-1alpha gene (HIF-1alpha) on prognosis
      in early-stage ccRCC (pT1a, pT1b, and pT2). Mutational analysis of the entire VHL
      sequence and the genotyping of HIF-1alpha C1772T SNP were performed together with
      VHL promoter methylation analysis and loss of heterozygosis (LOH) analysis at
      (3p25) locus. Data obtained were correlated with VHL and HIF-1alpha protein
      expression and with tumor-specific survival (TSS). VHL mutations, methylation
      status, and LOH were detected in 51, 11, and 12% of cases, respectively. Our
      results support the association between biallelic alterations and/or VHL
      silencing with a worse TSS. Moreover, we found a significant association between
      the HIF-1alpha C1772C genotype and a worse TSS. The same association was found
      when testing the presence of HIF-1alpha protein in the nucleus. Our results
      highlight the role of VHL/HIF-1alpha pathway in RCC and support the molecular
      heterogeneity of early-stage ccRCC. More important, we show the involvement of
      HIF-1alpha C1772T SNP in ccRCC progression.

PMID- 24446254
TI  - Alterations of oxidative phosphorylation complexes in astrocytomas.
AB  - The shift in cellular energy production from oxidative phosphorylation (OXPHOS)
      to glycolysis, even under aerobic conditions, called the Warburg effect, is a
      feature of most solid tumors. The activity levels of OXPHOS complexes and citrate
      synthase were determined in astrocytomas. A gradual decrease of citrate synthase
      and OXPHOS complexes was observed depending on tumor grade. In low-grade
      astrocytomas (WHO grade II), enzyme activities of citrate synthase, complex I,
      and complex V were comparable to those of normal brain tissue. A trend to reduced
      activities was observed for complexes II-IV. In glioblastoma (WHO grade IV),
      activities of citrate synthase and complexes I-IV were decreased by 56-92% as
      compared with normal brain. Immunohistochemical staining for porin revealed that
      the tumorpil of low-grade astrocytomas displays characteristics of the
      mitochondria-rich neuropil of normal brain tissue. In high-grade tumors (WHO
      grades III and IV), the tumorpil was characterized by severe morphologic
      alterations as well as loss of "pilem" structures. Specific alterations of OXPHOS
      complexes were observed in all astrocytic tumors by immunohistochemical analysis:
      80% of astrocytomas exhibited severe deficiency of complex IV; complex I showed a
      gradual reduction in amount with increasing tumor grade, whereas complex II
      showed reduced levels only in high-grade (WHO grade IV) tumors (9/12); complexes
      III and V did not show significant alterations compared with normal brain tissue.
      OXPHOS defects were present not only in the cell bodies of tumor cells but also
      in the pilem structures, indicating that the ramifications/protuberances
      (tumorpil) in general originate from tumor cells.

PMID- 24446255
TI  - Multifunctional core-shell silica nanoparticles for highly sensitive (19)F
      magnetic resonance imaging.
AB  - 19F magnetic resonance imaging (19F MRI) is useful for monitoring particular
      signals from biological samples, cells, and target tissues, because background
      signals are missing in animal bodies. Therefore, highly sensitive 19F MRI
      contrast agents are in great demand for their practical applications. However, we
      have faced the following challenges: 1) increasing the number of fluorine atoms
      decreases the solubility of the molecular probes, and 2) the restriction of the
      molecular mobility attenuates the 19F MRI signals. Herein, we developed novel
      multifunctional core-shell nanoparticles to solve these issues. They are composed
      of a core micelle filled with liquid perfluorocarbon and a robust silica shell.
      These core-shell nanoparticles have superior properties such as high sensitivity,
      modifiability of the surface, biocompatibility, and sufficient in vivo stability.
      By the adequate surface modifications, gene expression in living cells and tumor
      tissue in living mice were successfully detected by 19F MRI.

PMID- 24446256
TI  - Practical approaches to the ESI-MS analysis of catalytic reactions.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is a soft ionization technique
      commonly coupled with liquid or gas chromatography for the identification of
      compounds in a one-time view of a mixture (for example, the resulting mixture
      generated by a synthesis). Over the past decade, Scott McIndoe and his research
      group at the University of Victoria have developed various methodologies to
      enhance the ability of ESI-MS to continuously monitor catalytic reactions as they
      proceed. The power, sensitivity and large dynamic range of ESI-MS have allowed
      for the refinement of several homogenous catalytic mechanisms and could
      potentially be applied to a wide range of reactions (catalytic or otherwise) for
      the determination of their mechanistic pathways. In this special feature article,
      some of the key challenges encountered and the adaptations employed to counter
      them are briefly reviewed.

PMID- 24446257
TI  - Detection of histamine in beer by nano extractive electrospray ionization mass
      spectrometry.
AB  - In this study, rapid quantitative detection of histamine in beer was achieved by
      using nano extractive electrospray ionization mass spectrometry (nano EESI-MS)
      coupling with standard addition method. Based on the MS(2) experiment, histamine
      concentrations in three beer samples were determined to be 1.10 +/- 0.12 ug/ml,
      0.81 +/- 0.09 ug/ml and 0.79 +/- 0.09 ug/ml. The limit of detection for this
      method was calculated to be 0.02 ug/ml. These results show that this novel method
      can be used for direct, rapid and sensitive detection of histamine in beer
      without any tedious sample pretreatment.

PMID- 24446258
TI  - Quantification of intact covalently metal labeled proteins using ESI-MS/MS.
AB  - Mass spectrometric methods matured from the successful qualitative
      characterization of proteins in complex mixtures into methods for quantitative
      proteomics often based on chemical tags with stable isotope labeling. In the
      study presented here, we extended the application of lanthanide-ion-based tags
      from the quantification using inductively coupled plasma-MS into the
      quantification of labeled intact proteins using electrospray ionization (ESI)-MS
      and ESI-MS/MS. We applied the metal chelate tag MeCAT-iodoacetamide (IA)
      (1,4,7,10-tetraazacyclododecane N,N',N",N" '-tetra acetic acid with a IA reactive
      site). Labeled proteins were separated using C3-reversed phase-high-performance
      liquid chromatography interfaced to ESI-MS. We could prove that even large
      proteins were completely labeled at all available cysteine residues using MeCAT
      IA with only a small excess of reagent. Fragmentation of labeled proteins either
      using infrared multiphoton dissociation in Fourier transform ion cyclotron
      resonance-MS or higher-energy collision dissociation with an Orbitrap gave
      characteristic fragments. We used these fragments to quantify several intact
      proteins avoiding digestion. To demonstrate the applicability, human serum
      albumin was quantified in blood serum. The high-performance liquid
      chromatography/ESI-MS/MS quantification data were validated using inductively
      coupled plasma-MS. Because the metal within the tag may be any of the
      lanthanides, multiplexing capabilities are inherent.

PMID- 24446259
TI  - HPLC-MS/MS method for quantitative determination of the novel dual inhibitor of
      FGF and VEGF receptors E-3810 in tumor tissues from xenograft mice and human
      biopsies.
AB  - We developed and validated a high-performance liquid chromatography-tandem mass
      spectrometry analytical method to measure E-3810, a novel dual inhibitor of
      fibroblast growth factor receptor 1 and vascular endothelial growth factor
      receptor 1-3 in tissues and determined the drug concentration in a biopsy of
      human breast cancer for the first time. The method is a modification of our
      previous one in plasma to study the clinical pharmacokinetics of the drug during
      the phase I/II trial. In view of the changes in matrix, we applied a partial
      validation protocol to determine recovery, sensitivity, range of linearity,
      precision, accuracy and stability of the method over three runs in a mouse tumor
      tissue and liver. The recovery of E-3810 from liver or tumor homogenate was >69%,
      and the lower limit of quantification was 5 ng/ml. The method was linear in the
      concentration range 5.0-500.0 ng/ml, as demonstrated by a determination
      coefficient R(2) >= 0.9955. The range of the calibration curve was appropriate
      for the analysis, as demonstrated by the accuracy, which was between 91.4% and
      106.7%. Interday precision and accuracy on quality control samples at 9, 30 and
      300 ng/ml were 3.1-11.2% and 98.3-111.4%, respectively. The assay was applied
      successfully to determine the intratumor concentration of E-3810 in different
      mouse xenograft tumor models and in a biopsy of a patient with breast cancer
      included in the phase I/II trial of the drug. In mouse tumors, the concentrations
      of E-3810 were higher than necessary to exert antitumor activity in vitro (1 uM).
      Even more of interest was the result obtained in a human biopsy of few
      milligrams, where E-3810 reached 4.9 ug/g (11 uM).

PMID- 24446260
TI  - Wide-scope analysis of pesticide and veterinary drug residues in meat matrices by
      high resolution MS: detection and identification using Exactive-Orbitrap.
AB  - A multiresidue and multiclass method for the simultaneous determination of more
      than 350 compounds including pesticides, biopesticides and veterinary drugs in
      different meat matrices (beef, pork and chicken) by ultra-high performance liquid
      chromatography coupled to Orbitrap MS has been developed. In the present study,
      the determination of fragments was accomplished as an essential tool for a
      reliable identification of compounds using high resolution MS. To obtain these
      fragments, different strategies have been carried out in order to ensure an
      appropriate fragment assignment and identification. The analytical method is
      suitable for qualitative analysis, and it was also evaluated for quantitative
      analysis. Generic extraction conditions were optimized, obtaining adequate
      recovery and precision values for most of the studied analytes (>290). The limits
      of detection ranged from 2 to 16 ug kg(-1). Limits of quantification were 10 ug
      kg(-1) with the exception of few compounds with a higher value (50 or 100 ug kg(
      1)). Limits of identification were also established, and they ranged from 2 to
      150 ug kg(-1). This method was applied to the analysis of 18 meat samples and
      some veterinary drugs as enrofloxacin and sulfadiazine were detected and further
      identified/quantified (with triple quadrupole) in two different samples at 33 ug
      kg(-1) and trace levels, respectively. No pesticides were detected in the
      analyzed samples.

PMID- 24446261
TI  - MASSyPup--an 'out of the box' solution for the analysis of mass spectrometry
      data.
AB  - Mass spectrometry has evolved to a key technology in the areas of metabolomics
      and proteomics. Centralized facilities generate vast amount of data, which
      frequently need to be processed off-site. Therefore, the distribution of data and
      software, as well as the training of personnel in the analysis of mass
      spectrometry data, becomes increasingly important. Thus, we created a
      comprehensive collection of mass spectrometry software which can be run directly
      from different media such as DVD or USB without local installation. MASSyPup is
      based on a Linux Live distribution and was complemented with programs for
      conversion, visualization and analysis of mass spectrometry (MS) data. A special
      emphasis was put on protein analysis and proteomics, encompassing the measurement
      of complete proteins, the identification of proteins based on Peptide Mass
      Fingerprints (PMF) or LC-MS/MS data, and de novo sequencing. Another focus was
      directed to the study of metabolites and metabolomics, covering the detection,
      identification and quantification of compounds, as well as subsequent statistical
      analyses. Additionally, we added software for Mass Spectrometry Imaging (MSI),
      including hardware support for self-made MSI devices. MASSyPup represents a
      'ready to work' system for teaching or MS data analysis, but also represents an
      ideal platform for the distribution of MS data and the development of related
      software. The current Live DVD version can be downloaded free of charge from
      http://www.bioprocess.org/massypup.

PMID- 24446262
TI  - The unusual hydrogen-deuterium exchange of alpha-carbon protons in N-substituted
      glycine-containing peptides.
AB  - Hydrogens connected to alpha-carbon (alpha-C) of amino acid residues are usually
      resistant to hydrogen-deuterium exchange (HDX) unless reaction conditions promote
      racemization. Although N-methylglycine (sarcosine) residue has been found in
      biologically active peptide such as cyclosporine, to the best of our knowledge,
      the HDX of alpha-C protons of this residue was not explored yet. Here, we
      presented a new and efficient methodology of alpha-C deuteration in sarcosine
      residues under basic aqueous conditions. The deuterons, introduced at alpha-C
      atom, do not undergo back-exchange in acidic aqueous solution. The electrospray
      ionization-MS and MS/MS experiments on proposed model peptides confirmed the HDX
      at alpha-C and revealed the unexpected hydrogen scrambling in sarcosine
      containing peptides. Although the observed HDX of alpha-C protons is only
      successful in N-acylglycine when the amide possesses a certain degree of
      alkylation, it offers a new approach to the analysis of sarcosine-containing
      peptides such as cyclosporine.

PMID- 24446263
TI  - Real time monitoring of accelerated chemical reactions by ultrasonication
      assisted spray ionization mass spectrometry.
AB  - Ultrasonication has been used to accelerate chemical reactions. It would be ideal
      if ultrasonication-assisted chemical reactions could be monitored by suitable
      detection tools such as mass spectrometry in real time. It would be helpful to
      clarify reaction intermediates/products and to have a better understanding of
      reaction mechanism. In this work, we developed a system for ultrasonication
      assisted spray ionization mass spectrometry (UASI-MS) with an ~1.7 MHz ultrasonic
      transducer to monitor chemical reactions in real time. We demonstrated that
      simply depositing a sample solution on the MHz-based ultrasonic transducer, which
      was placed in front of the orifice of a mass spectrometer, the analyte signals
      can be readily detected by the mass spectrometer. Singly and multiply charged
      ions from small and large molecules, respectively, can be observed in the UASI
      mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup
      accelerates the chemical reactions while being monitored via UASI-MS. The
      feasibility of using this approach for real-time acceleration/monitoring of
      chemical reactions was demonstrated. The reactions of Girard T reagent and
      hydroxylamine with steroids were used as the model reactions. Upon the deposition
      of reactant solutions on the ultrasonic transducer, the intermediate/product ions
      are readily generated and instantaneously monitored using MS within 1 s.
      Additionally, we also showed the possibility of using this reactive UASI-MS
      approach to assist the confirmation of trace steroids from complex urine samples
      by monitoring the generation of the product ions.

PMID- 24446264
TI  - Detection of efaproxiral (RSR13) and its metabolites in equine by liquid
      chromatography tandem mass spectrometry.
AB  - Efaproxiral (RSR 13) is an experimental synthetic allosteric modifier of
      haemoglobin (Hb) that acts by increasing the release of oxygen from Hb to the
      surrounding tissues. It has been shown to increase maximum oxygen uptake
      (VO(2max)) in a canine skeletal muscle model. The ability to increase maximal
      muscle oxygen uptake makes efaproxiral a potential performance-enhancing agent
      and is therefore prohibited by the World Anti-Doping Agency. In this study, a
      method for the detection and elimination of efaproxiral in equine plasma and
      urine after a 2.5 g intravenous administration of efaproxiral is described. Post
      administration plasma and urine samples were collected up to 120 h. Efaproxiral
      was detected up to 120 h in urine and up to 78 h in plasma. In plasma, the peak
      concentration was 42 ug/ml and detected at 5 min post administration. In urine,
      the peak concentration was 2.8 mg/ml and detected at 0-1 h post administration. A
      validated liquid chromatography tandem mass spectrometry method was used for the
      quantitation of efaproxiral in equine plasma and urine. The limit of detection of
      the method is 0.05 ng/ml in plasma and 0.1 ng/ml in urine. The method is highly
      sensitive and specific with good precision, accuracy and recovery. The manuscript
      also describes the systematic identification of efaproxiral metabolites detected
      in post administration equine urine samples. The metabolites were identified by
      use of enhanced mass spectra and enhanced product ion scans. Both positive and
      negative mode ionizations were utilized for metabolite identification and
      plausible fragmentation pathways were proposed for the phase 1 metabolite
      identified. In addition to free efaproxiral, one phase 1 metabolite and two phase
      2 metabolites were identified in post administration urine.

PMID- 24446265
TI  - Novel glutathione conjugates of phenyl isocyanate identified by ultra-performance
      liquid chromatography/electrospray ionization mass spectrometry and nuclear
      magnetic resonance.
AB  - Phenyl isocyanate is a highly reactive compound that is used as a reagent in
      organic synthesis and in the production of polyurethanes. The potential for
      extensive occupational exposure to this compound makes it important to elucidate
      its reactivity towards different nucleophiles and potential targets in the body.
      In vitro reactions between glutathione and phenyl isocyanate were studied. Three
      adducts of glutathione with phenyl isocyanate were identified using ultra
      performance liquid chromatography/electrospray ionization mass spectrometry and
      nuclear magnetic resonance (NMR). Mass spectrometric data for these adducts have
      not previously been reported. Nucleophilic attack on phenyl isocyanate occurred
      via either the cysteinyl thiol group or the glutamic acid alpha-amino group of
      glutathione. In addition, a double adduct was formed by the reaction of both
      these moieties. NMR analysis confirmed the proposed structure of the double
      adduct, which has not previously been described. These results suggest that
      phenyl isocyanate may react with free cysteines, the alpha-amino group and also
      with lysine residues whose side chain contains a primary amine.

PMID- 24446266
TI  - Separation and fragmentation study of isocoproporphyrin derivatives by UHPLC-ESI
      exact mass MS/MS and identification of a new isocoproporphyrin sulfonic acid
      metabolite.
AB  - Isocoproporphyrin and its derivatives are commonly used as biomarkers of
      porphyria cutanea tarda, heavy metal toxicity and hexachlorobenzene (HCB)
      intoxication in humans and animals. However, most are isobaric with other
      porphyrins and reference materials are unavailable commercially. The structural
      characterisation of these porphyrins is important but very little data is
      available. We report here the separation and characterisation of
      isocoproporphyrin, deethylisocoproporphyrin, hydroxyisocoproporphyrin and
      ketoisocoproporphyrin, isolated in the faeces of rats fed with a diet containing
      HCB, by ultra high performance liquid chromatography-exact mass tandem mass
      spectrometry (UHPLC-MS/MS). Furthermore, we report the identification and
      characterisation of a previously unreported porphyrin metabolite,
      isocoproporphyrin sulfonic acid isolated in the rat faeces. The measured mass-to
      charge ratio (m/z) of the precursor ion was m/z 735.2338, corresponding to a
      molecular formula of C36H39N4O11S with an error of 0.3 ppm from the calculated
      m/z 735.2336. The MS/MS data was consistent with an isocoproporphyrin sulfonic
      acid structure, derived from dehydroisocoproporphyrinogen by sulfonation of the
      vinyl group. The metabolite was present in a greater abundance than other
      isocoproporphyrin derivatives and may be a more useful biomarker for HCB
      intoxication.

PMID- 24446267
TI  - Mass spectrometry imaging: a new vision in differentiating Schistosoma mansoni
      strains.
AB  - Schistosomiasis is a neglected disease with large geographic distribution
      worldwide. Among the several different species of this parasite, S. mansoni is
      the most common and relevant one; its pathogenesis is also known to vary
      according to the worms' strain. High parasitical virulence is directly related to
      granulomatous reactions in the host's liver, and might be influenced by one or
      more molecules involved in a specific metabolic pathway. Therefore, better
      understanding the metabolic profile of these organisms is necessary, especially
      for an increased potential of unraveling strain virulence mechanisms and
      resistance to existing treatments. In this report, MALDI-MSI and the metabolomic
      platform were employed to characterize and differentiate two Brazilian S. mansoni
      strains: males and females from Belo Horizonte (BH) and from Sergipe (SE). By
      performing direct analysis, it is possible to distinguish the sex of adult worms,
      as well as identify the spatial distribution of chemical markers. Phospholipids,
      diacylglycerols and triacylglycerols were located in specific structures of the
      worms' bodies, such as tegument, suckers, reproductive and digestive systems.
      Lipid profiles were found to be different both between strains and males or
      females, giving specific metabolic fingerprints for each group. This indicates
      that biochemical characterization of adult S. mansoni may help narrowing-down the
      investigation of new therapeutic targets according to worm composition, molecule
      distribution and, therefore, aggressiveness of disease.

PMID- 24446268
TI  - Origins of the reassortant 2009 pandemic influenza virus through proteotyping
      with mass spectrometry.
AB  - The application of a proteotyping approach employing high resolution mass
      spectrometry based is shown to be able to determine the gene origin of all major
      viral proteins in a triple reassortant pandemic 2009 influenza strain. Key to
      this approach is the identification of unique swine-host-specific signature and
      indicator peptides that are characteristic of influenza viruses circulating in
      North American and Eurasian swine herds in the years prior to the 2009 influenza
      pandemic. These swine-and human pandemic-specific signatures enable the origins
      of viral proteins in a clinical virus specimen to be determined and such strains
      to be rapidly and directly differentiated from other co-circulating seasonal
      influenza viruses from the same period. The proteotyping strategy offers
      advantages over traditional RT-PCR-based approaches that are currently the
      mainstay of influenza surveillance at the molecular level.

PMID- 24446269
TI  - Ionic strength of electrospray droplets affects charging of DNA oligonucleotides.
AB  - The fundamental aspects of charging in electrospray ionization (ESI) are hotly
      debated. In the present study, ESI charging of DNA oligonucleotides was explored
      in both positive (ESI+) and negative (ESI-) polarity using mass spectrometry
      detection. Single-stranded 12-mer CCCCAATTCCCC in buffer solution (aqueous NH4Ac,
      100 mM) produced similar charge state distribution (CSD) in either ESI+ or ESI-.
      Similarity of CSD in ESI+ and ESI- was also observed for the double-stranded 12
      mer CGCGAATTCGCG. By adding typical low-vapor reagents (e.g. m-nitro benzyl
      alcohol, m-NBA; sulfolane) into the same buffer solution (<0.5% w/v), both
      CCCCAATTCCCC and CGCGAATTCGCG revealed strong supercharging (SC) effect in ESI-,
      while very little or no SC effect was observed in ESI+. With either sulfolane or
      m-NBA, the CGCGAATTCGCG duplex dissociated into single strands in ESI-. No SC was
      observed in both ESI+ and ESI- for thermally denatured CGCGAATTCGCG duplex in NH4
      Ac buffer without the reagents. These findings are difficult to reconcile with
      the earlier model, which attributes SC in aqueous buffer solution to the
      conformational changes of analytes. Our observations suggest that the ionic
      strength of ESI droplets strongly affects the CSD of biopolymers such as DNA
      oligonucleotides and that SC effect is related to the depletion of ionic strength
      during the ESI process.

PMID- 24446270
TI  - Enantiomeric differentiation of beta-amino alcohols under electrospray ionization
      mass spectrometric conditions.
AB  - The enantiomeric differentiation of a series of chiral beta-amino alcohols (A) is
      attempted, for the first time, by applying the kinetic method using L-proline, L
      tryptophan, 4-iodo-L-phenylalanine or 3, 5-diiodo-L-tyrosine as the chiral
      references (Ref) and Cu(2+) or Ni(2+) ion (M) as the central metal ion. The
      trimeric diastereomeric adduct ions, [M+(Ref)2+A-H](+), formed under electrospray
      ionization conditions, are subjected for collision-induced dissociation (CID)
      experiments. The products ions, formed by the loss of either a reference or an
      analyte, detected in the CID spectra are evaluated for the enantiomeric
      differentiation. All the references showed enantiomeric differentiation and the
      R(chiral) values are better for the aromatic alcohols than for aliphatic
      alcohols. Notably, the R(chiral) values of the aliphatic amino alcohols enhanced
      when Ni(2+) is used as the central metal ion. The experimental results are well
      supported by computational studies carried out on the diastereomeric dimeric
      complexes. The computational data of amino alcohols is correlated with that of
      amino acids to understand the structural interaction of amino alcohols with
      reference molecule and central metal ion and their role on the stabilization of
      the dimeric complexes. Application of flow injection MS/MS method is also
      demonstrated for the enantiomeric differentiation of the amino alcohols.

PMID- 24446273
TI  - Estradiol administration to ovariectomized rats potentiates mephedrone-induced
      disruptions of nonspatial learning.
AB  - Mephedrone (4-methylmethcathinone) has been found in several over-the-counter
      products that are abused by humans, but very little is known about its behavioral
      effects and abuse liability. The present study examined the effects of mephedrone
      (1-10 mg/kg) on learning in female rats, as well as its interaction with the
      ovarian hormone estradiol. More specifically, female rats were trained to respond
      under a multiple schedule of repeated acquisition and performance of response
      sequences and then ovariectomized. Following ovariectomy, mephedrone dose-effect
      curves were obtained during periods of 17beta-estradiol administration and
      periods without estradiol administration. Unlike mephedrone, which was
      administered acutely (i.p.) before the experimental sessions, 17beta-estradiol
      was administered via subcutaneous Silastic capsules containing 25% 17beta
      estradiol and 75% cholesterol. In general, mephedrone produced dose-dependent
      rate-decreasing and error-increasing effects in the acquisition and performance
      components of the schedule in all subjects. However, when estradiol was present,
      three of the four rats were more sensitive to the rate-decreasing effects of
      mephedrone, and all of the subjects were more sensitive to its error-increasing
      effects. These data indicate that estradiol can potentiate the disruptive effects
      of mephedrone on both the acquisition and performance of complex behavior in
      female rats. 

PMID- 24446274
TI  - Shape-memory effect by specific biodegradable polymer blending for biomedical
      applications.
AB  - Specific biodegradable polymers having shape-memory properties through "polymer
      blend" method are investigated and their shape-switching in body temperature (37 
      degrees C) is characterized. Poly(L-lactide-co-caprolactone) (PLCL) and poly(L
      lactide-co-glycolide) (PLGA) are dissolved in chloroform and the films of several
      blending ratios of PLCL/PLGA are prepared by solvent casting. The shape-memory
      properties of films are also examined using dynamic mechanical analysis (DMA).
      Among the blending ratios, the PLCL50/PLGA50 film shows good performance of shape
      fixity and shape-recovery based on glass transition temperature. It displays that
      the degree of shape recovery is 100% at 37  degrees C and the shape recovery
      proceeds within only 15 s. In vitro biocompatibility studies are shown to have
      good blood compatibility and cytocompatibility for the PLCL50/PLGA50 films. It is
      expected that this blended biodegradable polymer can be potentially used as a
      material for blood-contacting medical devices such as a self-expended vascular
      polymer stents and vascular closure devices in biomedical applications.

PMID- 24446275
TI  - Towards new response criteria in neuroendocrine tumors: which changes in MRI
      parameters are associated with longer progression-free survival after
      radioembolization of liver metastases?
AB  - PURPOSE: To evaluate the association of therapy-related changes in imaging
      parameters with progression-free survival (PFS) of patients with unresectable
      liver metastases from neuroendocrine tumors (NETLMs). MATERIALS AND METHODS:
      Forty-five radioembolized patients (median age: 62 years; range: 43-75) received
      a pre- and 3 months posttherapeutic magnetic resonance imaging (MRI) examination.
      The latter were evaluated for tumor size, arterial enhancement, and necrosis
      pattern. Influences of therapy-related changes on PFS were analyzed. Statistical
      analysis included Student's t-test, Wilcoxon test, Cox regression analysis, and
      Kaplan-Meier curves. RESULTS: The median percentage decrease in sum of diameters
      was 9.7% (range: 43.9% decrease to 15.4% increase). Twenty-one patients (47%)
      showed increased necrosis. Three parameters were associated with significantly
      longer PFS: a decrease of diameter (hazard ratio [HR]: 0.206; 95% confidence
      interval [CI]: 0.058-0.725; P = 0.0139), a decrease in tumor arterial enhancement
      (HR: 0.143; 95% CI: 0.029-0.696; P = 0.0160), and an increase in necrosis after 3
      months (HR: 0.321; 95% CI: 0.104-0.990; P = 0.0480). Multivariate analysis
      revealed that changes in diameter and arterial enhancement have complementary
      information and are associated independently with long PFS. CONCLUSION: A
      decrease both in sum of diameters and arterial enhancement of metastases, as well
      as an increase in necrosis, are associated with significantly longer PFS after
      radioembolization.

PMID- 24446276
TI  - Signal detection of potentially drug-induced acute liver injury in children using
      a multi-country healthcare database network.
AB  - BACKGROUND: Data mining in spontaneous reporting databases has shown that drug
      induced liver injury is infrequently reported in children. OBJECTIVES: Our
      objectives were to (i) identify drugs potentially associated with acute liver
      injury (ALI) in children and adolescents using electronic healthcare record (EHR)
      data; and (ii) to evaluate the significance and novelty of these associations.
      METHODS: We identified potential cases of ALI during exposure to any
      prescribed/dispensed drug for individuals <18 years old from the EU-ADR network,
      which includes seven databases from three countries, covering the years 1996
      2010. Several new methods for signal detection were applied to identify all
      statistically significant associations between drugs and ALI. A drug was
      considered statistically significantly associated with ALI, using all other time
      as a reference category, if the 95% CI lower band of the relative risk was >1 and
      in the presence of at least three exposed cases of ALI. Potentially new signals
      were distinguished from already known associations concerning ALI (whether in
      adults and/or in the paediatric population) through manual review of published
      literature and drug product labels. RESULTS: The study population comprised
      4,838,146 individuals aged <18 years, who contributed an overall 25,575,132
      person-years of follow-up. Within this population, we identified 1,015 potential
      cases of ALI. Overall, 20 positive drug-ALI associations were detected. The
      associations between ALI and domperidone, flunisolide and human insulin were
      considered as potentially new signals. Citalopram and cetirizine have been
      previously described as hepatotoxic in adults but not in children, while all
      remaining associations were already known in both adults and children.
      CONCLUSIONS: Data mining of multiple EHR databases for signal detection confirmed
      known associations between ALI and several drugs, and identified some potentially
      new signals in children that require further investigation through formal
      epidemiologic studies. This study shows that EHRs may complement traditional
      spontaneous reporting systems for signal detection and strengthening.

PMID- 24446277
TI  - Pharmacovigilance for children's sake.
AB  - Child age-specific information on efficacy and risk of medicines can be limited
      for healthcare professionals and patients. It is therefore very important to make
      the best use of a risk planned approach to the pharmacological treatment of
      children. This means pharmacovigilance in the broadest sense of gaining the best
      data from the use of medicines in clinical practice. We consider issues that
      complicate safe medication use in paediatric care, as well as current progress
      and provide suggestions for building knowledge within paediatric
      pharmacovigilance to be used to minimise patient harm. The continuous development
      in children constitutes a challenge to prescribing and administering age-suitable
      doses for individual children. Children are not only different from adults but
      differ vastly within their own age group. Physical growth during childhood is
      apparent to the eye, but less obvious is the ongoing maturation of organ function
      important for drug disposition and action. Systematic issues such as medication
      errors, off-label use and the lack of age-suitable formulations are considerable
      obstacles for safe medication use in paediatrics. The recognition of emerging
      adverse drug reactions could be more challenging in developing children.
      Initiatives to improve the situation have been made by the WHO and regulators in
      the USA and EU. Age-specific changes in physiology, pharmacology and psychology,
      as well as systematic issues specific for children need to be considered in the
      work of assessing spontaneous reports in children. Pharmacovigilance needs to
      broaden its aims considerably beyond merely capturing new associations between
      drugs and events, and encompass careful collection on patient characteristics and
      circumstances around the reported adverse drug reaction to provide essential
      information that will give clues on how to prevent harm to children. 

PMID- 24446278
TI  - The new insights from DPP-4 inhibitors: their potential immune modulatory
      function in autoimmune diabetes.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents
      that are widely used in clinical practice to improve glycemic control and protect
      beta-cell function in patients with type 2 diabetes. DPP-4 is also known as
      lymphocyte cell surface protein CD26 and plays an important role in T-cell
      immunity. Autoimmune diabetes, a T-cell mediated organ-specific disease, is
      initiated by the imbalance between pathogenic and regulatory T-lymphocytes. DPP-4
      inhibitors can suppress pathogenic effects of Th1 and Th17 cells and up-regulate
      Th2 cells and regulatory T cells, which play a critical role in ameliorating
      autoimmune diabetes. This provides a basis for the potential use of DPP-4
      inhibitors in the treatment of autoimmune diabetes. Recent studies suggest that
      DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1
      diabetic mouse models. However, there are few clinical studies on the treatment
      of autoimmune diabetes with DPP-4 inhibitors. Further studies are warranted to
      confirm the therapeutic effects of DPP-4 inhibitors on autoimmune diabetes in
      humans.

PMID- 24446279
TI  - The translational biology of remyelination: past, present, and future.
AB  - Amongst neurological diseases, multiple sclerosis (MS) presents an attractive
      target for regenerative medicine. This is because the primary pathology, the loss
      of myelin-forming oligodendrocytes, can be followed by a spontaneous and
      efficient regenerative process called remyelination. While cell transplantation
      approaches have been explored as a means of replacing lost oligodendrocytes, more
      recently therapeutic approaches that target the endogenous regenerative process
      have been favored. This is in large part due to our increasing understanding of
      (1) the cell types within the adult brain that are able to generate new
      oligodendrocytes, (2) the mechanisms and pathways by which this achieved, and (3)
      an emerging awareness of the reasons why remyelination efficiency eventually
      fails. Here we review some of these advances and also highlight areas where
      questions remain to be answered in both the biology and translational potential
      of this important regenerative process.

PMID- 24446280
TI  - Dental stem cells--characteristics and potential.
AB  - Soft dental tissues have been identified as easily accessible sources of
      multipotent postnatal stem cells. Dental stem cells are mesenchymal stem cells
      (MSC) capable of differentiating into at least three distinct cell lineages:
      osteo/odontogenic, adipogenic and neurogenic. They express various markers
      including those specific for MSC, embryonic stem cells and neural cells. Five
      different types of dental stem cells have been isolated from mature and immature
      teeth: dental pulp stem cells, stem cells from exfoliated deciduous teeth,
      periodontal ligament stem cells, stem cells from apical papilla and dental
      follicle progenitor cells. Dental stem cells may be used in dental tissue
      engineering including dental, enamel and periodontal tissue regeneration. They
      could also be used as a promising tool in potential treatment of
      neurodegenerative, ischemic and immune diseases.

PMID- 24446281
TI  - Rational perturbation of the fluorescence quantum yield in emission-tunable and
      predictable fluorophores (Seoul-Fluors) by a facile synthetic method involving C
      H activation.
AB  - Fluorescence imaging enables the uniquely sensitive observation of functional-
      and molecular-recognition events in living cells. However, only a limited range
      of biological processes have been subjected to imaging because of the lack of a
      design strategy and difficulties in the synthesis of biosensors. Herein, we
      report a facile synthesis of emission-tunable and predictable Seoul-Fluors, 9
      aryl-1,2-dihydrolopyrrolo[3,4-b]indolizin-3-ones, with various R(1) and R(2)
      substituents by coinage-metal-catalyzed intramolecular 1,3-dipolar cycloaddition
      and subsequent palladium-mediated C?H activation. We also showed that the quantum
      yields of Seoul-Fluors are controlled by the electronic nature of the
      substituents, which influences the extent of photoinduced electron transfer. On
      the basis of this understanding, we demonstrated our design strategy by the
      development of a Seoul-Fluor-based chemosensor 20 for reactive oxygen species
      that was not accessible by a previous synthetic route. 

PMID- 24446282
TI  - Eliciting preferences to inform patient-centred policies: the case of psoriasis.
AB  - OBJECTIVE: To assess patient preferences for psoriasis treatment features and to
      investigate the heterogeneity of preferences among patients with different socio
      demographic and disease-related characteristics. METHODOLOGY: A discrete choice
      experiment was conducted on adult patients with moderate to severe plaque-type
      psoriasis during a routine visit to their physician at 15 centres in Italy. We
      investigated the preferences of patients with respect to five treatment
      attributes: (1) mode and frequency of administration; (2) time to improvement;
      (3) time free of symptoms; (4) unintended life expectancy reduction resulting
      from treatment; and (5) monthly treatment cost. The heterogeneity of preferences
      was investigated in a mixed logit model with normally distributed random
      coefficients. RESULTS: Overall, patients preferred the subcutaneous or
      intravenous route of administration (versus oral administration) and treatments
      that took less time to show improvement, ensured a longer time free of symptoms,
      involved a lesser reduction in life expectancy and had lower costs. There was
      significant preference heterogeneity for all attributes. The cost attribute was
      found to be significantly more important to females and to older patients (above
      60 years of age). Older patients placed significantly greater emphasis on reduced
      life expectancy, whereas the time free of symptoms was significantly less
      important to them than to patients under 60 years of age. Patients with higher
      scores on the Dermatology Life Quality Index (DLQI) placed higher value on the
      time free of symptoms than those with lower DLQI scores. For the overall sample,
      the marginal willingness to pay (WTP) for a month's reduction in the time to
      improvement was <euro>32.4, whereas the WTP for one additional month without
      symptoms was significantly higher (<euro>68.2). CONCLUSION: Patient-centred
      policies should consider the heterogeneity of patients' expectations to identify
      individualized treatments that would aid in optimizing patient satisfaction and
      wellbeing, as well as overall treatment effectiveness.

PMID- 24446283
TI  - Behavioral functions of stimuli signaling transitions across rich and lean
      schedules of reinforcement.
AB  - On multiple fixed-ratio schedules, pausing is extended at the start of a
      component ending in a small reinforcer (a lean component) but only when this
      component follows a component ending in a large reinforcer (a rich component). In
      two experiments, we assessed whether a stimulus correlated with a lean component
      is aversive and how its function is affected by the preceding component. In
      Experiment 1, pigeons responded on mixed fixed-ratio schedules ending in large or
      small reinforcers. Observing responses converted the mixed schedule to a multiple
      one by producing a stimulus correlated with the current component. Overall, the
      lean stimulus did not suppress observing, suggesting that it was not sufficiently
      aversive. In Experiment 2, an escape procedure was used, and pigeons could
      convert a multiple schedule to a mixed one by pecking a key to remove the
      discriminative stimuli. Pigeons escaped from the lean-schedule stimulus more than
      they did from the rich one. For two pigeons, this effect was enhanced when a rich
      component preceded the lean stimulus. The results indicate that a stimulus
      correlated with the leaner of two reinforcement schedules can acquire aversive
      functions, but observing and escape procedures may differ in their abilities to
      detect this effect. 

PMID- 24446284
TI  - Gender flip-flop association between genetic variations of NEDD4L and metabolic
      syndrome in the Kazakh general population.
AB  - Genetic variation is thought to contribute to etiology of metabolic syndrome
      (MS). Neural precursor cell expressed developmentally downregulated 4-like gene
      (NEDD4L) is a candidate gene for MS. This study investigated the relationship
      between variations of NEDD4L and MS in the Kazakh, which is an ideal population
      to study the genetic mechanisms of complex diseases such as MS. We screened the
      promoter and exons of NEDD4L in 48 Kazakh individuals with MS to identify
      representative variations. By genotyping the representative variations [271420T>C
      (rs2288774), 271454A>G (rs2288775), and 296921-296923delTTG] in the Kazakh
      general population, we conducted a case-control study. In female subjects, the
      distribution of genotypes and alleles of rs2288775 and 296921-296923delTTG
      differed significantly between the MS pacients and controls. In male subjects,
      the genotype distributions of 296921-296923delTTG were significantly different
      between the MS pacients and controls in the dominant model (P = 0.047). After
      adjustment for age, smoking, and drinking, multivariate logistic regression
      analysis showed that rs2288775 was significantly associated with MS [for the A/A
      genotype, odds ratio (OR) = 3.296, P = 0.011] in female subjects. For 296921
      296923delTTG, the I/D+D/D genotype was the high-risk genotype for MS in female
      subjects (OR = 2.791, P = 0.035) and was a protective factor for MS in male
      subjects (OR = 0.580, P = 0.045). The 296921-296923delTTG variation of NEDD4L is
      a gender flip-flop associated with MS in Kazakh individuals. The A allele of
      rs2288775 may be an independent risk factor for MS in Kazakh women. The results
      suggest that the genetic variations of NEDD4L might be involved in the
      pathogenesis of MS. 

PMID- 24446285
TI  - Efficient identification of ornamental peach cultivars using RAPD markers with a
      manual cultivar identification diagram strategy.
AB  - One of the most important uses of DNA markers is cultivar identification.
      However, no DNA fingerprint analysis strategy is available for making DNA markers
      helpful in practical plant cultivar identification, especially for the
      identification of a large number of cultivars. We developed a manual cultivar
      identification diagram strategy for efficient identification of plant cultivars,
      from which a cultivar identification diagram (CID) of genotyped plant individuals
      can be constructed manually. This CID could be used as a reference for quick
      identification of plant cultivars of interest. We used 11-mer RAPD primers to
      amplify DNA samples of 32 ornamental peach genotypes; all the cultivars were well
      distinguished by fingerprints from 6 primers. The utility of this CID was
      verified by identification of three randomly chosen groups of cultivars among the
      32 ones that we selected. This CID generated will be useful for the
      identification of commercially important ornamental peach cultivars. 

PMID- 24446286
TI  - Genetic diversity and relationships among different tomato varieties revealed by
      EST-SSR markers.
AB  - The genetic diversity and relationship of 42 tomato varieties sourced from
      different geographic regions was examined with EST-SSR markers. The genetic
      diversity was between 0.18 and 0.77, with a mean of 0.49; the polymorphic
      information content ranged from 0.17 to 0.74, with a mean of 0.45. This indicates
      a fairly high degree of diversity among these tomato varieties. Based on the
      cluster analysis using unweighted pair-group method with arithmetic average
      (UPGMA), all the tomato varieties fell into 5 groups, with no obvious
      geographical distribution characteristics despite their diverse sources. The
      principal component analysis (PCA) supported the clustering result; however,
      relationships among varieties were more complex in the PCA scatterplot than in
      the UPGMA dendrogram. This information about the genetic relationships between
      these tomato lines helps distinguish these 42 varieties and will be useful for
      tomato variety breeding and selection. We confirm that the EST-SSR marker system
      is useful for studying genetic diversity among tomato varieties. The high degree
      of polymorphism and the large number of bands obtained per assay shows that SSR
      is the most informative marker system for tomato genotyping for purposes of
      rights/protection and for the tomato industry in general. It is recommended that
      these varieties be subjected to identification using an SSR-based manual cultivar
      identification diagram strategy or other easy-to-use and referable methods so as
      to provide a complete set of information concerning genetic relationships and a
      readily usable means of identifying these varieties. 

PMID- 24446287
TI  - An efficient regeneration protocol for Agrobacterium-mediated transformation of
      melon (Cucumis melo L.).
AB  - An efficient selection and plant regeneration protocol for Agrobacterium-mediated
      transformation, using cotyledon node zone-stem connection region of melon, has
      been developed. The new Agrobacterium-mediated transformation methodology,
      independent of organ culture, used the entire germinated seed as explants. The
      transformation system was maximized to maintain the integrity of melon itself,
      thus avoiding the limitations of traditional tissue culture methods. The
      transformation was carried out under a non-sterile environment. The incorporation
      of a selectable marker (neomycin phosphotransferase II) into the genome of
      transgenic plants was confirmed by PCR and Southern blot analyses. The
      transformation frequency based on the PCR was 13%. Transgenic melon plants were
      usually detected by PCR in less than 1 month after Agrobacterium inoculation, and
      seeds could be harvested in 3 months. The growth characteristics and morphology
      of the transgenic plants were identical to the untransformed wild-type plants.
      This method would be beneficial for facilitating the characteristics of gene
      functions and for boosting the manipulation of melon transformation for
      commercial purposes. 

PMID- 24446288
TI  - Identification and functional analysis of differentially expressed genes related
      to obesity using DNA microarray.
AB  - We looked for differentially expressed genes at different stages of preadipocyte
      differentiation and examined their functions, based on DNA microarrays of
      preadipocytes obtained from healthy subjects undergoing cosmetic liposuction. We
      downloaded gene expression profile GSE25910 from the Gene Expression Omnibus
      database and identified the differentially expressed genes with packages in R
      language. The selected differentially expressed genes were further analyzed using
      bioinformatics methods. Comparing gene expression at different stages of
      preadipocytes differentiation, we found that expression of 668 and 1007 genes
      were altered in middle and late stages compared with the early stage,
      respectively. Function analysis revealed that the differentially expressed genes
      were mainly related to fatty acid metabolic processes in the former two stages. 

PMID- 24446289
TI  - Quaternary origin and genetic divergence of the endemic cactus Mammillaria
      pectinifera in a changing landscape in the Tehuacan Valley, Mexico.
AB  - The endemic Mexican cactus, Mammillaria pectinifera, shows low dispersal
      capabilities and isolated populations within the highly dissected landscape of
      Tehuacan Valley. These characteristics can restrict gene flow and act upon the
      genetic divergence and speciation in arid plants. We conducted a phylogeographic
      study to determine if the origin, current distribution, and genetic structure of
      M. pectinifera were driven by Quaternary geomorphic processes. Sequences of the
      plastids psbA-trnH and trnT-trnL obtained from 66 individuals from seven
      populations were used to estimate genetic diversity. Population differentiation
      was assessed by an analysis of molecular variance. We applied a stepwise
      phylogenetic calibration test to determine whether species origin and genetic
      divergence among haplotypes were temporally concordant with recognizable episodes
      of geomorphic evolution. The combination of plastid markers yielded six
      haplotypes, with high levels of haplotype diversity (h = 0.622) and low
      nucleotide diversity (pi = 0.00085). The populations were found to be genetically
      structured (F(ST) = 0.682; P < 0.00001), indicating that geographic isolation and
      limited dispersal were the primary causes of genetic population differentiation.
      The estimated origin and divergence time among haplotypes were 0.017-2.39 and
      0.019-1.237 mya, respectively, which correlates with Pleistocene tectonics and
      erosion events, supporting a hypothesis of geomorphically-driven geographical
      isolation. Based on a Bayesian skyline plot, these populations showed long term
      demographic stability, indicating that persistence in confined habitats has been
      the main response of this species to landscape changes. We conclude that the
      origin and haplotype divergence of M. pectinifera were a response to local
      Quaternary geomorphic evolution.

PMID- 24446290
TI  - Genetic diversity of Angiopolybia pallens (Lepeletier) (Hymenoptera, Vespidae,
      Polistinae) explained by the disjunction of South American rainforests.
AB  - Angiopolybia pallens is a swarm-founding wasp that occurs in Atlantic and
      Amazonian rainforests, which have been isolated from each other by a large arid
      corridor in central Brazil since the Tertiary. In this study, we used data from
      polymerase chain reaction-restriction fragment length polymorphism of 16S rDNA to
      infer some aspects of the genetic diversity and evolutionary history of this
      social wasp population. Samples collected across the species range in both
      rainforests showed remarkable differences that separated them into two distinct
      haplogroups. However, some samples from isolated areas in northeastern Bahia were
      more related to Amazonian lineages than to southern Bahia populations. Vicariant
      divergenc is discussed under South American rainforests biogeographical
      proposals. 

PMID- 24446291
TI  - Identifying differentially expressed genes and pathways in two types of non-small
      cell lung cancer: adenocarcinoma and squamous cell carcinoma.
AB  - Non-small cell lung carcinoma, NSCLC, accounts for 80-85% of lung cancers. NSCLC
      can be mainly divided into two types: adenocarcinoma (ADC) and squamous cell
      carcinoma (SCC). The purpose of our study was to identify and differentiate the
      pathogenesis of ADC and SCC at the molecular level. The gene expression profiles
      of ADC and SCC were downloaded from Gene Expression Omnibus under accession No.
      GSE10245. Accordingly, differentially expressed genes (DEGs) were identified by
      the limma package in R language. In addition, DEGs were functionally analyzed by
      Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A
      total of 4124 DEGs were identified, including CDK1, CDK2, CDK4, and SKP2. The
      DEGs were mainly involved in 16 pathways related to cell proliferation, cell
      signal transduction and metabolism. We conclude that the molecular mechanisms of
      ADC and SCC are considerably different, and that they are involved in immune
      response, cell signal transduction, metabolism, cell division, and cell
      proliferation. Therefore, the two diseases should be treated differently. This
      study offers new insight into the diagnosis and therapy of these two types of
      lung cancer. 

PMID- 24446292
TI  - Meta-analysis of associations between the TP53 Arg72Pro polymorphism with risk of
      head and neck carcinomas based on case-control studies.
AB  - Genetic factors have been shown to play a role in the development of head and
      neck cancers (HNCs). However, studies investigating the association between the
      TP53 Arg72Pro polymorphism and HNCs susceptibility have yielded conflicting
      results. Hence, we performed a meta-analysis of all eligible studies (up to
      January 1, 2012) to derive a more precise estimation of this association in order
      to increase understanding of the possible risk factors of HNCs. Twenty-seven case
      control studies involving 3966 cases and 4387 controls were included in our
      analysis. Overall, no evidence of association was observed between the TP53
      Arg72Pro single nucleotide polymorphism (SNP) and the risk of HNCs in any genetic
      model (Arg/Arg vs Pro/Pro: odds ratio (OR) = 0.83, 95% confidence interval (CI):
      0.65-1.06; Arg/Pro vs Pro/Pro: OR = 0.88, 95%CI= 0.70-1.10; Arg/Arg+Arg/Pro vs
      Pro/Pro: OR = 0.87, 95%CI= 0.70-1.09; Arg/Arg vs Arg/Pro+Pro/Pro: OR = 0.95,
      95%CI= 0.82-1.11). Nevertheless, the TP53 Arg72Pro polymorphism shows diverse
      effects across different subtypes of HNCs. For example, there was a lack of
      association of this polymorphism with oral cavity cancer, whereas a significant
      association with nasopharyngeal cancer was observed. Results of this meta
      analysis suggest that the TP53 Arg72Pro polymorphism might have different effects
      on the risk of various subtypes of HNCs. 

PMID- 24446294
TI  - Molecular cloning, expression, and regulation of the ovalbumin gene in pigeon
      oviduct epithelial cells.
AB  - The full-length pigeon ovalbumin (OVA) gene cDNA was cloned and sequenced by
      reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification
      of cDNA ends. A 386-amino acid protein was predicted for the obtained sequence,
      which had 67% identity with the chicken protein. Similar to chicken OVA, the
      pigeon OVA gene is a non-inhibitory serine protease inhibitor. Quantitative PCR
      analysis revealed that pigeon OVA mRNA was highly expressed in the oviduct, and
      trace amounts were detected in other tissues. During the reproductive cycle,
      pigeon oviduct OVA mRNA expression reached its peak during the egg-laying stage,
      decreased with brooding, and then increased again during the squab-feeding
      period. Moreover, the relative OVA expression level in pigeon oviduct epithelial
      cells could be upregulated by a constant concentration of steroid hormones. 

PMID- 24446295
TI  - No association between FGD1 gene polymorphisms and intellectual developmental
      disability in the Qinba mountain area.
AB  - FGD1 encoding a guanine nucleotide exchange factor, specifically activates Rho
      GTPase cell division cycle 42 (Cdc42). Dysfunction of FGD1 causes Aarskog-Scott
      syndrome (MIM #305400), an X-linked disorder that may affect bone and
      intellectual development. However, the relationship between FGD1 and intellectual
      developmental disorders (IDD) remains unclear. The purpose of this study was to
      investigate the genetic association between the FGD1 polymorphism and IDD.
      Working with families from the Qinba mountain area where the occurrence of IDD is
      higher than the average in China, we analyzed 456 samples from 130 nuclear
      families, effectively controlling for stratification and environmental factors.
      Five SNP loci (rs2230265, rs7881608, rs2239809, rs6614244, and rs2284710) were
      selected that were well distributed within the FGD1 gene. Genotyping was
      performed through single-strand conformation polymorphism and restriction
      fragment length polymorphism. The data were analyzed with transmission
      disequilibrium tests. In the Qinba mountain area, no significant association was
      observed between IDD and allele or genotype frequencies, or the haplotype of the
      5 SNP loci of the FGD1 gene. The results indicate that FGD1 may not be a
      monogenetic X-linked factor in IDD. Further studies are required to investigate
      its role in intellectual development based on its specific interactions with
      Cdc42 or other partner proteins contributing to IDD. 

PMID- 24446296
TI  - Polymorphic microsatellite markers in the false kelpfish Sebastiscus marmoratus:
      isolation, characterization, and cross-species amplification.
AB  - A (GT/CA)13-microsatellite-enriched genomic library of the false kelpfish
      Sebastiscus marmoratus was constructed, and 20 polymorphic microsatellite loci
      were isolated and characterized. The polymorphisms were investigated in 48 wild
      individuals from a single population collected from the northern Yellow Sea. The
      numbers of alleles per locus varied from 4-22 with an average of 9. The observed
      and expected heterozygosities of each locus ranged from 0.196-0.958 and from
      0.487-0.942, with an average of 0.693 and 0.765, respectively. One locus
      significantly deviated from Hardy-Weinberg equilibrium, and one pair of loci was
      in linkage disequilibrium determined by Bonferroni's correction. Cross-species
      amplification was also conducted in the related species Inimicus japonicus,
      collected from East China Sea. The result showed that six loci could be amplified
      from I. japonicus DNAs. These polymorphic markers would be useful for assessment
      of genetic variation and population structure of scorpionfish. 

PMID- 24446298
TI  - Biochip analysis of prostate cancer.
AB  - Microarray expression analysis was used to forecast the roles of differentially
      co-expressed genes (DCG) and DCG and links in the pathogenesis of prostate
      cancer. In addition, we demonstrate that the relationship between transcriptional
      factors (TFs) and their targets can be considered a key factor in determining the
      difference between primary and metastatic prostate cancer. Regulatory impact
      factors were adopted to calculate the impact of TF. We identified 5 TFs and 29
      target genes important in the transition between normal prostate and primary
      prostate cancer and 2 TFs and 7 target genes important in the transition between
      primary and metastatic prostate cancer. These results suggest that it may be
      possible to predict the clinical behavior of prostate cancer based on gene
      expression analysis. 

PMID- 24446297
TI  - -174G/C polymorphism in the interleukin-6 promoter is differently associated with
      prostate cancer incidence depending on race.
AB  - Interleukin-6 (IL-6), a pro-inflammatory cytokine, is involved in prostate cancer
      progression, including androgen independence. Serum IL-6 levels also correlate
      with prostate tumor burden, prostate-specific antigen levels and metastasis.
      Since circulating cytokine levels vary considerably inter-individually, such
      variation could be linked to genetic factors, including genetic polymorphism. The
      -174G>C/rs1800795 polymorphism in the IL-6 promoter is functionally relevant in
      terms of transcriptional regulation and disease association. We investigated a
      possible association of the -174G/C polymorphism with prostate cancer. Since
      significant racial disparities exist in prostate cancer incidence, we also
      investigated this association between the -174G/C polymorphism and prostate
      cancer in Caucasians and African-Americans, separately. Direct sequencing of the
      PCR amplicon from genomic DNA was used for genotyping rs1800795 in all subjects
      [age-matched controls (N = 140) and prostate cancer patients (N = 164)]. Sample
      size and power was calculated using the PGA software. We found the GG genotype to
      be associated with increased risk of prostate cancer in Caucasian subjects,
      whereas the CC genotype was associated with increased risk in the African
      American sample set. Such a dimorphic genotypic association with cancer and race
      is unique and suggests a complex gene-gene and gene-environment interaction. 

PMID- 24446299
TI  - Association between a single nucleotide polymorphism of the XRCC1 gene and
      hepatocellular carcinoma susceptibility in the Chinese Han population.
AB  - The human X-ray repair cross-complementing protein 1 (XRCC1) gene is a
      potentially gene determining hepatocellular carcinoma (HCC) susceptibility. The
      purpose of this study was to evaluate the association between XRCC1 and
      susceptibility to HCC. The association of XRCC1 polymorphisms with HCC
      susceptibility was investigated in 460 HCC patients and 463 controls using the
      created restriction site-polymerase chain reaction method. Our results indicate
      that the c.1471G>A variant could be detected and that the allele and genotype
      frequencies were statistically different between cases and controls. The AA
      genotype was strongly associated with increased HCC susceptibility as compared
      with the GG wild genotype (OR = 2.214, 95%CI = 1.493-3.283, chi(2) = 15.97, P <
      0.0001). In addition, significantly increased HCC susceptibility was also found
      in a dominant and recessive model (P < 0.01). The allele A could contribute to
      HCC susceptibility compared with the G allele (OR = 1.480, 95%CI = 1.224-1.789,
      chi(2) = 16.44, P = 0.0001). Results from this study indicate that the XRCC1
      c.1471G>A polymorphism is associated with HCC susceptibility in the Chinese Han
      population. Future studies on larger populations are essential to confirm this
      association. 

PMID- 24446300
TI  - Movement patterns and genetic diversity of wild and reintroduced common dormice,
      Muscardinus avellanarius.
AB  - Movement is an important life history trait that can have an impact on local
      adaptation, and other evolutionary phenomena. We used a combination of nestbox
      survey data and genetic techniques (genotyping at 10 microsatellite loci) to
      quantify patterns of movement in common dormice Muscardinus avellanarius at two
      distinct sites in the UK: 1) Bontuchel (a natural population) and 2) Wych
      (captive-bred individuals that were reintroduced to this site), over three
      consecutive years (2006-2008). Both methods revealed a consistent pattern of sex
      biased movement (movements by adult males and females) in both populations that
      allowed isolation-by-distance genetic structure to develop within 1 km. The
      similarity of data from captive-bred and natural individuals indicated that ex
      situ programing has not significantly altered the natural movement behavior of
      common dormice; consequently, the two populations could be managed with the same
      conservation strategies. We also found that the reintroduced dormice in Wych
      maintained relatively high levels of genetic diversity. This first report of
      movement patterns in reintroduced and natural populations of M. avellanarius
      combining genetic and field-survey data highlights the role of genetic studies in
      the investigation of ecological behaviour and for conservation management. 

PMID- 24446301
TI  - A single nucleotide polymorphism of the TNRC9 gene associated with breast cancer
      risk in Chinese Han women.
AB  - A single nucleotide polymorphism (SNP) in the TNRC9 gene was identified as a
      breast cancer susceptibility genetic variant in recent genome-wide association
      studies of women of European ancestry. We investigated whether TNRC9
      polymorphisms are associated with risk of breast cancer in Chinese women of the
      Han nationality. We genotyped the SNPs rs3803662, rs1362548, rs1123428 in 870
      women, including 388 breast cancer patients and 482 healthy controls, via the PCR
      single strand conformation polymorphism procedure and by sequence detection. We
      found that the T allele and the TT genotype of the SNP rs38033662 is
      significantly associated with risk for breast cancer in Chinese Han women;
      however, no significant association was found for rs1362548 or rs1123428. We
      conclude that SNP rs3803662 is a putative risk factor for breast cancer in
      Chinese Han women. 

PMID- 24446302
TI  - Molecular cloning and expression pattern of the DjStag gene in the planarian
      Dugesia japonica during embryonic development.
AB  - We examined STAG-related gene (DjStag) expression in the planarian Dugesia
      japonica. This species is common in Far Eastern countries. The DjStag cDNA
      includes 1362 bp and contains a 489-bp open reading frame corresponding to a
      deduced protein of 162 amino acids, with a 170-bp 5'-UTR and a 703-bp 3'-UTR.
      Phylogenetic analysis showed that DjStag is an STAG/STAG-like member. We examined
      the expression pattern of DjStag in this planarian during embryonic development
      by whole-mount in situ hybridization. DjStag was detected in embryonic cells in
      the germ band at early embryo stages. The number of DjStag-positive embryonic
      cells increased in stage 5. Later, it was mainly expressed in lateral region
      parenchyma. In juveniles, extensive expression of DjStag was observed not only in
      the head and tail regions, but also in the parenchyma between the epidermis and
      the gastrodermis. We conclude that DjStag is expressed in the cellular subset
      that will become the neoblast cells of the adult flatworm. DjStag may play an
      essential role in spatial and temporal regulation during planarian embryonic
      development. 

PMID- 24446303
TI  - Application of genomics and proteomics in drug target discovery.
AB  - Gene medicine is making breakthroughs in health questions that have baffled
      humanity for centuries. To understand and utilize gene medicine, it is necessary
      to realize its action against targets at the molecular level. Currently, many
      methods can be used to discover drug targets; among these, genomic and proteomic
      methods are the two most important. In this study, we introduced how to discover
      drug targets by genomic and proteomic methods in detail. These contents are
      beneficial for understanding and utilizing the two methods to discover new drug
      targets of gene medicine. 

PMID- 24446304
TI  - Thunbergia laurifolia extract minimizes the adverse effects of toxicants by
      regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression
      in HepG2 cells.
AB  - Thunbergia laurifolia (TL) is widely used as an antidote in Thai traditional
      medicine against toxic substances such as alcohol, pesticides, arsenic, and
      strychnine. We found that the lyophilized form of TL in 80% ethanol possessed the
      antioxidant levels within the range 23,163.9 +/- 1457.4 Trolox equivalents mM/kg
      dry mass and 899.8 +/- 14.5 gallic acid equivalents mM/kg dry mass using the
      oxygen radical absorbance capacity assay and the Folin Ciocalteu phenol assay,
      respectively. TL extract (TLE) at a high dose (3000 mg/L) induced cytotoxicity
      according to the neutral red assay and the MTT assay. However, TLE doses of 800
      3000 mg/L could reduce intracellular oxidative stress in a dose-dependent manner
      (P < 0.05) using the dichlorodihydrofluorescein diacetate assay. TLE
      significantly enhanced the mRNA expression of CYP1A1, CYP1A2, CYP2B6, CYP3A4, and
      PPARg, but it significantly inhibited the mRNA expression of CYP3A7, CYP2D6, and
      CYP2E1 (P < 0.05) by reverse transcription-polymerase chain reaction. Moreover,
      TLE could increase the activity of a multidrug transporter, P-glycoprotein, which
      accelerated the excretion of toxic substances from HepG2 cells. It is suggested
      that TLE may be beneficial for detoxification by reducing oxidative stress,
      minimizing toxicity by regulating the expression CYP450 mRNAs for suitable
      production of CYP450 isoenzymes, and increasing PPARgamma mRNA expression and P
      glycoprotein activity in HepG2 cells, thereby maintaining xenobiotic
      biotransformation balance. 

PMID- 24446305
TI  - An SLE patient with prolactinoma and recurrent granulomatous mastitis
      successfully treated with hydroxychloroquine and bromocriptine.
AB  - Granulomatous mastitis (GM) is a rare benign mammary lesion in which autoimmunity
      and hyperprolactinemia are considered possible etiological factors. GM has a high
      frequency of relapse and may lead to chronic ulceration and fistula if not
      treated properly. Here we report a case of a 22-year-old systemic lupus
      erythematosus (SLE) patient with three years' disease duration, stable on
      prednisone and hydroxychloroquine, who was found to have prolactinoma and
      recurrent GM after she discontinued medication on her own accord. The patient
      subsequently recovered and remained free of GM relapse under treatment of
      prednisone, hydroxychloroquine and bromocriptine. Though autoimmune disorders and
      prolactinoma were reported in GM, a coexisting condition of SLE, prolactinoma,
      and granulomatous mastitis has rarely been observed in one patient. We suggest
      our case as an illustrative example of the complex interaction between
      autoimmunity, neuroendocrine dysfunction, and manifestations in the breast:
      Immunological disturbances in the background of SLE, coupled with elevated
      prolactin levels secondary to a prolactinoma, may have predisposed the patient to
      the development of GM. The mammary lesion recovered and maintained free of
      relapse under immunosuppressive and antiprolactinemic therapy. 

PMID- 24446307
TI  - Arthropods on plants in a fragmented Neotropical dry forest: a functional
      analysis of area loss and edge effects.
AB  - Loss and fragmentation of natural ecosystems are widely recognized as the most
      important threats to biodiversity conservation, with Neotropical dry forests
      among the most endangered ecosystems. Area and edge effects are major factors in
      fragmented landscapes. Here, we examine area and edge effects and their
      interaction, on ensembles of arthropods associated to native vegetation in a
      fragmented Chaco Serrano forest. We analyzed family richness and community
      composition of herbivores, predators, and parasitoids on three native plant
      species in 12 fragments of varying size and at edge/interior positions. We also
      looked for indicator families by using Indicator Species Analysis. Loss of family
      richness with the reduction of forest fragment area was observed for the three
      functional groups, with similar magnitude. Herbivores were richer at the edges
      without interaction between edge and area effects, whereas predators were not
      affected by edge/interior position and parasitoid richness showed an interaction
      between area and position, with a steeper area slope at the edges. Family
      composition of herbivore, predator, and parasitoid assemblages was also affected
      by forest area and/or edge/interior situation. We found three indicator families
      for large remnants and five for edges. Our results support the key role of forest
      area for conservation of arthropods taxonomic and functional diversity in a
      highly threatened region, and emphasize the need to understand the interactions
      between area and edge effects on such diversity. 

PMID- 24446308
TI  - Processing, signaling, and physiological function of chemerin.
AB  - Chemerin is an immunomodulating factor secreted predominantly by adipose tissue
      and skin. Processed by a variety of proteases linked to inflammation, it
      activates the G-protein coupled receptor chemokine-like receptor 1 (CMKLR1) and
      induces chemotaxis in natural killer cells, macrophages, and immature dendritic
      cells. Recent developments revealed the role of the nonsignaling chemerin
      receptor C-C chemokine receptor-like 2 (CCRL2) in inflammation. Besides further
      research establishing its link to inflammatory skin conditions such as psoriasis,
      functions in healthy skin have also been reported. Here, the current
      understanding of chemerin processing, signaling and physiological function has
      been summarized, focusing on the regulation of its activity, its different
      receptors and its controversially discussed role in diseases.

PMID- 24446306
TI  - The anatomic basis for ventricular arrhythmia in the normal heart: what the
      student of anatomy needs to know.
AB  - The traditional route for teaching cardiac anatomy involves didactic instruction,
      cadaver dissections, and familiarization with the main structure and
      relationships of the cardiac chambers, valves, and vasculature. In contemporary
      cardiac electrophysiology, however, a very different view of anatomy is required
      including details rarely appreciated with a general overview. In this review, we
      discuss the critical advances in cardiac electrophysiology that were possible
      only because of understanding detailed anatomic relationships. While we briefly
      discuss the clinical relevance, we explain in depth the necessary structural
      information for the student of clinical anatomy. Interspersed through the text
      are boxes that highlight and summarize the critical pieces of knowledge to be
      borne in mind while studying the fascinating structural anatomy of the human
      heart.

PMID- 24446309
TI  - Immune mechanisms in hypertension.
AB  - Low grade inflammation may have a key role in the pathogenesis of hypertension
      and cardiovascular disease. Several studies showed that both innate and adaptive
      immune systems may be involved, being T cells the most important players.
      Particularly, the balance between Th1 effector lymphocytes and Treg lymphocytes
      may be crucial for blood pressure elevation and related organ damage development.
      In the presence of a mild elevation of blood pressure, neo-antigens are produced.
      Activated Th1 cells may then contribute to the persistent elevation of blood
      pressure by affecting vasculature, kidney and perivascular fat. On the other
      hand, Tregs represent a lymphocyte subpopulation with an anti-inflammatory role,
      being their activity crucial for the maintenance of cardiovascular homeostasis.
      Indeed, Tregs were demonstrated to be able to protect from blood pressure
      elevation and from the development of organ damage, including micro and
      macrovascular alterations, in different animal models of genetic or experimental
      hypertension. In the vasculature, inflammation leads to vascular remodeling
      through cytokine activity, smooth muscle cell proliferation and oxidative stress.
      It is also known that a consistent part of ischemia-reperfusion-induced acute
      kidney injury is mediated by inflammatory infiltration and that Treg cell
      infusion have a protective role. Also the central nervous system has an important
      role in the maintenance of cardiovascular homeostasis. In conclusion,
      hypertension development involves chronic inflammatory process. Knowledge of
      cellular and molecular players in the progression of hypertension has
      dramatically improved in the last decade, by assessing the central role of innate
      and adaptive immunity cells and proinflammatory cytokines driving the development
      of target organ damage. The new concept of role of immunity, especially
      implicating T lymphocytes, will eventually allow discovery of new therapeutic
      targets that may improve outcomes in hypertension and cardiovascular or renal
      disease in humans and uncover an entirely novel approach in the treatment of
      hypertension and vascular disease.

PMID- 24446310
TI  - Identification of living Legionella pneumophila using species-specific metabolic
      lipopolysaccharide labeling.
AB  - Legionella pneumophila is a pathogenic bacterium involved in regular outbreaks
      characterized by a relatively high fatality rate and an important societal
      impact. Frequent monitoring of the presence of this bacterium in environmental
      water samples is necessary to prevent these epidemic events, but the traditional
      culture-based detection and identification method requires up to 10 days.
      Reported herein is a method allowing identification of Legionella pneumophila by
      metabolic lipopolysaccharide labeling which targets, for the first time, a
      precursor to monosaccharides that are specifically present within the O-antigen
      of the bacterium. This new approach allows easy detection of living Legionella
      pneumophila, while other Legionella species are not labeled. 

PMID- 24446312
TI  - Tunable mesoporous bilayer photonic resins with chiral nematic structures and
      actuator properties.
AB  - Chiral nematic structures with different helical pitch from layer to layer are
      embedded into phenol-formaldehyde bilayer resin composite films using cellulose
      nanocrystals (CNCs) as templates. Selective removal of CNCs results in mesoporous
      resins with different pore size and helical pitch between the layers.
      Consequently, these materials exhibit photonic properties by selectively
      reflecting lights of two different wavelengths and concomitant actuation
      properties. 

PMID- 24446311
TI  - BRAF kinase domain mutations are present in a subset of chronic myelomonocytic
      leukemia with wild-type RAS.
AB  - The frequency of RAS mutations in chronic myelomonocytic leukemia (CMML) suggests
      that activation of the MAPK pathway is important in CMML pathogenesis.
      Accordingly, we hypothesized that mutations in other members of the MAPK pathway
      might be overrepresented in RAS(wt) CMML. We performed targeted next generation
      sequencing analysis on 70 CMML patients with known RAS mutation status. The study
      group included 37 men and 33 women with a median age of 67.8 years (range, 28-86
      years). Forty patients were RAS(wt) and 30 were RAS(mut) ; the latter included
      KRAS = 17; NRAS = 12; KRAS + NRAS = 1. Five patients (7.1% of total group; 12.5%
      of RAS(wt) group) with RAS(wt) had kinase domain BRAF mutations. The BRAF
      mutations were of missense type and involved exon 11 in one patient and exon 15
      in four patients. All BRAF(mut) patients had CMML-1 with low-risk cytogenetic
      findings. Two (40%) of the five patients with BRAF(mut) patients transformed to
      acute myeloid leukemia during follow-up. In summary, we demonstrate that a subset
      of patients with RAS(wt) CMML harbors BRAF kinase domain mutations that are
      potentially capable of activating the MAPK signaling pathway.

PMID- 24446313
TI  - Response to Epstein's comment on "heterogeneity in action".

PMID- 24446314
TI  - Effects of the ginkgo biloba extract on the superoxide dismutase activity and
      apoptosis of endothelial progenitor cells from diabetic peripheral blood.
AB  - Although ginkgo biloba extract (GBE) was shown to have antioxidant effects,
      little has been reported on the ability to GBE to help endothelial progenitor
      cells (EPCs) resist oxidative stress. The present study evaluated the influence
      of different concentrations of GBE on superoxide dismutase (SOD) and apoptosis of
      diabetic peripheral blood EPCs. Twenty-five diabetic patients without any
      vascular complications were included in the experimental group, while 15 healthy
      adults made up the control group. Peripheral blood mononuclear cells were
      isolated with density gradient centrifugation, and, after in vitro
      differentiation, were determined to be EPCs using FITC-UEA-I and Dil-Ac-LDL dual
      staining. After the colony and fusiform adherent cells were observed, on day 7,
      various concentrations of ginkgo biloba extract (0, 10, 25, 50 mg/L) were added
      to the culture medium for a 24-h incubation. EPC-SOD activity and apoptosis were
      subsequently detected. We found that within the experimental group, GBE
      significantly improved SOD activity within EPCs and reduced the rate of
      apoptosis. These effects became more obvious with increasing GBE concentrations
      (25 mg/L, P < 0.05; 50 mg/L, P < 0.01). GBE also improved SOD activity and
      reduced the rate of apoptosis within EPCs of the control group; however, the
      changes were not statistically significant. We conclude that GBE can improve SOD
      activity and reduce the rate of apoptosis of EPCs within the peripheral blood of
      diabetic patients, effects that are dose-dependent. 

PMID- 24446315
TI  - Pharmacogenetics of DNA repair gene polymorphisms in non-small-cell lung
      carcinoma patients on platinum-based chemotherapy.
AB  - Individual differences in chemosensitivity and clinical outcome of non-small-cell
      lung carcinoma (NSCLC) patients can be influenced by host-inherited factors. We
      investigated the impact of XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPD
      Arg156Arg, XPD Asp312Asn, XPD Asp711Asp, and XPD Lys751Gln gene polymorphisms on
      treatment efficacy in 375 NSCLC patients on platinum-based chemotherapy. We also
      examined progression-free survival and overall survival. The gene polymorphisms
      were analyzed by duplex PCR. The patients with XRCC1 399A/A had a significantly
      better response to chemotherapy. Individuals with XPD 711 Asp and XPD 312 Asn
      alleles responded poorly to chemotherapy when compared with the wide-type
      genotype. The adjusted hazard ratio (HR) in the Cox regression model was
      calculated. The XRCC1 399A/A polymorphism was associated with better progression
      free survival and overall survival of NSCLC patients (HR=0.61 and 0.55). On the
      other hand, the XPD 711 Asp allele was associated with poorer progression free
      survival and overall survival compared to the C/C genotype, with HRs of 1.89 and
      1.90. The XPD 312 Asn allele was found to be associated with non-significantly
      reduced survival of NSCLC patients (HR = 1.73). In conclusion, we found the
      polymorphisms of XRCC1 and XPD to be related to the efficacy of platinum-based
      chemotherapy in NSCLC patients. This information should aid in therapeutic
      decisions for individualized therapy in NSCLC cases. 

PMID- 24446316
TI  - Transcriptomic response of cowpea bruchids to N-acetylglucosamine-specific
      lectins.
AB  - Griffonia simplicifolia lectin II (GSII) and wheat germ agglutinin (WGA) are N
      acetylglucosamine-binding lectins. Previous studies demonstrated that they have
      anti-insect activity, a property potentially useful in pest control. To gain some
      insight into the insect response to dietary lectins, we performed transcriptomic
      analysis using the cowpea bruchid (Callosobruchus maculatus) midgut microarray
      platform we built. Compared to the nonnutritional cellulose treatment, dietary
      lectins induced more profound changes in gene expression. Ingestion of relatively
      high doses of lectins for 24 h resulted in alteration of gene expression involved
      in sugar and lipid metabolism, transport, development, defense, and stress
      tolerance. Metabolic genes were largely downregulated. Moreover, we observed
      disorganized microvilli resulting from ingestion of WGA. This morphological
      change is consistent with the lectin-induced changes in genes related to midgut
      epithelial cell repair. In addition, suboptimal nutrient conditions may serve as
      a stress signal to trigger senescence processes, leading to growth arrest and
      developmental delay. 

PMID- 24446317
TI  - Studies on the preparative isolation and stability of seven main anthocyanins
      from Yan 73 grape.
AB  - BACKGROUND: [corrected] Seven anthocyanin monomers of Yan 73 grape were separated
      using preparative HPLC and identified by UPLC-ESI-MS/MS. The stabilities of the
      seven isolated anthocyanins to light, temperature and pH were also investigated.
      RESULTS: Seven anthocyanin monomers were successfully isolated with an Xbridge
      Prep C18 column on a preparative scale. The pigments delphinidin-3-O-glucoside,
      malvidin-3-O-acetylglucoside and malvidin-3-O-coumarylglucoside were yielded in a
      one-step separation by preparative HPLC, with purities up to 99.9%, 91.7% and
      95.5%, respectively. The pigments cyanidin-3-O-glucoside, petunidin-3-O
      glucoside, peonidin-3-O-glucoside, and malvidin-3-O-glucoside were further
      purified with another elution method and their purities were all improved up to
      99.9%. Monomeric anthocyanin degradation fitted a first-order reaction model. The
      seven isolated anthocyanins were significantly more stable in the dark than under
      light. High temperature was also unfavourable for the stability of anthocyanins.
      The anthocyanins were more stable at lower pH than at higher pH. In addition,
      among these anthocyanins, delphinidin-3-O-glucoside, malvidin-3-O-acetylglucoside
      and malvidin-3-O-coumarylglucoside were more susceptible to light, heat, and pH
      than the others. CONCLUSION: A simple and clean isolation method of seven
      anthocyanin monomers from Yan 73 grape was established. The stabilities of the
      seven anthocyanin monomers to light, temperature and pH were different, but the
      trends in changes were similar.

PMID- 24446318
TI  - Atom-economic, regiodivergent, and stereoselective coupling of imidazole
      derivatives with terminal allenes.
AB  - New Rh- and Pd-catalyzed regiodivergent and stereoselective intermolecular
      coupling reactions of imidazole derivatives with mono-substituted allenes are
      herein reported. Using a Rh(I)/Josiphos system, perfect regioselectivities and
      high enantiomeric excess were obtained, while a Pd(II)/dppf system gave linear
      products with high regioselectivities and high E/Z selectivities. This method
      permits the atom economic synthesis of valuable branched and linear allylic
      imidazole derivatives.

PMID- 24446319
TI  - Bleeding, a call to action.

PMID- 24446320
TI  - The real world?

PMID- 24446321
TI  - An ounce of prevention....

PMID- 24446322
TI  - Balloon-assisted tracking for transradial catheterization: beating the curve.

PMID- 24446323
TI  - Vascular access closure--size still matters.

PMID- 24446324
TI  - Transcatheter occlusion of the patent ductus arteriosus in infants: experimental
      testing of a new Amplatzer device.
AB  - OBJECTIVES: This study assessed the feasibility and efficacy of implanting a new
      miniaturized nitinol device to occlude the patent ductus arteriosus (PDA) in a
      newborn porcine model. BACKGROUND: Transcatheter device closure is the standard
      of care for PDA in older children and adults. Currently available technology is
      not designed for the newborn infant. METHODS: The Amplatzer Duct Occluder II 0.5
      is a new transcatheter Nitinol device without fabric designed to close the PDA
      with small aortic and pulmonary artery structures. The device was implanted in 8
      infant pigs (average weight 2,400 g) after balloon dilation of PDA (average
      diameter 2.7 mm, average length 5.8 mm) with immediate, ~ 7, ~ 30, and ~ 90 day
      follow-up by echocardiography, angiography, and final pathological examination.
      Half were implanted arterial, and half venous. RESULTS: The device was
      successfully implanted in all animals. There was complete occlusion of the PDA in
      all cases without obstruction of the pulmonary arteries or aorta. There was
      complete late endothelialization without thrombus. The only complication was
      transection of a femoral artery accessed by cutdown. CONCLUSIONS: The success of
      this animal study confirms safety and feasibility of the Amplatzer Duct Occluder
      II 0.5 (now known as the ADO II AS) for use when the aorta and pulmonary arteries
      are small. Consideration can be given to transcatheter closure of the PDA in
      preterm and other small infants with this device.

PMID- 24446325
TI  - Alcohol septal ablation versus surgical myectomy for HCM--the controversy
      continues.

PMID- 24446326
TI  - Have we found the ideal plug for post-TAVR paravalvular leaks?

PMID- 24446327
TI  - Mitral stenosis following MitraClip procedure: is it preventable?

PMID- 24446328
TI  - Decompressing the left atrium to relieve the right ventricle.

PMID- 24446329
TI  - A pilot study evaluating the efficacy of a group social skills program for
      survivors of childhood central nervous system tumors using a comparison group and
      teacher reports.

PMID- 24446330
TI  - Trends in aggregate cancer incidence rates in relation to screening and possible
      overdiagnosis: a word of caution.
AB  - BACKGROUND: Overdiagnosis in breast cancer screening is a topic of debate.
      Researchers often estimate trends in incidence prior to screening and project
      these to predict incidence during the screening epoch. METHODS: Data was obtained
      from the Cancer Registry of Norway and the Norwegian Breast Cancer Screening
      Programme. Using breast cancer incidence prior to screening in Norway (1976
      1995), incidence trends were estimated from age-period and age-cohort models.
      These estimates were used to predict the incidence of breast cancer in five-year
      age and period groups in the screening epoch (1996-2009). RESULTS: Excess numbers
      of cancers in the screening age range (6,876 cancers), and deficits in women
      above and below the screening age range (1,947 cancers) were observed. However,
      only part of the observed differences between the observed and the expected
      incidence can be explained by screening, as evidenced by numbers of excess
      cancers greater than the numbers of screen-detected cancers in some age groups
      and time periods. CONCLUSION: There are potential errors in estimation of
      overdiagnosis from screening if individual data on screening exposure and
      detection mode are not taken into account. For reliable estimates of
      overdiagnosis, it is necessary to compare excess incidence in the screening
      period in those actually screened with the corresponding excess in those not
      screened. This is the subject of ongoing research.

PMID- 24446331
TI  - Highly active aluminium catalysts for the formation of organic carbonates from
      CO2 and oxiranes.
AB  - Al(III) complexes of amino-tris(phenolate) ligand scaffolds have been prepared to
      attain highly Lewis acidic catalysts. Combination of the aforementioned systems
      with ammonium halides provides highly active catalysts for the synthesis of
      organic carbonates through addition of carbon dioxide to oxiranes with initial
      turnover frequencies among the highest reported to date within the context of
      cyclic carbonate formation. Density functional theory (DFT) studies combined with
      kinetic data provides a rational for the relative high activity found for these
      Al(III) complexes, and the data are consistent with a monometallic mechanism. The
      activity and versatility of these Al(III) complexes has also been evaluated
      against some state-of-the-art catalysts and the combined results compare
      favorably in terms of catalyst construction, stability, activity, and
      applicability. 

PMID- 24446332
TI  - Cytotoxic triosmium carbonyl clusters: a structure-activity relationship study.
AB  - A structure-activity relationship (SAR) study of the triosmium carbonyl cluster
      Os3 (CO)10 (NCCH3 )2 was carried out with a series of clusters of the general
      formula Os3 (CO)12-n Ln , cationic osmium clusters and a hemi-labile maltolato-Os
      cluster. The SAR results showed that good solubility in DMSO and at least one
      vacant site are required for cytotoxicity. In vitro evaluation of these new
      compounds showed that some are selectively active against estrogen receptor (ER)
      independent MDA-MB-231 breast cancer cell lines relative to ER-dependent MCF-7
      breast cancer cells, suggesting that the compounds have a different biological
      target specific to MDA-MB-231 cells. In particular, the maltolato cluster
      exhibits strong antiproliferative activity, with an IC50 value of 3 MUM after
      only 24 h incubation. Additionally, biochemical assays conducted with the
      cationic cluster show that it induces apoptosis, although a biological target has
      not yet been identified. Further research to establish the molecular targets of
      these compounds and to develop improved organometallic clusters as potential
      breast cancer therapeutics is underway. 

PMID- 24446333
TI  - Food cravings among bariatric surgery candidates.
AB  - PURPOSE: Food cravings are common, more prevalent in the obese, and may differ in
      those who pursue surgical treatment for obesity. Food craving tools are most
      often validated in non-clinical, non-obese samples. METHODS: In this
      retrospective study, 227 bariatric surgery candidates at a large medical center
      completed the Food Cravings Questionnaire-Trait (FCQ-T). The aim was to explore
      the factor structure of the FCQ-T. RESULTS: Principal components analysis with
      varimax rotation revealed a seven-factor structure that explained 70.89 % of the
      variance. The seven factors were: (1) preoccupation with food, (2) emotional
      triggers, (3) environmental cues, (4) loss of control, (5) relief from negative
      emotions, (6) guilt, and (7) physiological response. The preoccupation with food
      factor accounted for 49.46 % of the variance in responses. CONCLUSIONS: Unlike
      other populations, food cravings in bariatric surgery candidates appear to be
      related most to preoccupations with food.

PMID- 24446334
TI  - Synthesis and pharmacological evaluation of novel 1'-[2-(difluoromethoxy)benzyl]
      2'H,5'H-spiro[8-azabicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-diones and
      their derivatives.
AB  - A series of novel 1'-[2-(difluoromethoxy)benzyl]-2'H,5'H-spiro[8
      azabicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-dione substituted hydantoins (5
      32) were synthesized using an appropriate synthetic route and characterized by
      elemental analysis and spectral data. The novel molecules were screened for
      anticonvulsant activity in mice by maximal electroshock (MES) and subcutaneous
      pentylenetetrazol (ScPTZ)-induced seizure tests. The neurotoxicity was assessed
      using the rotarod method. Compounds 9, 10, 18, 30, and 31 exhibited
      anticonvulsant potency against MES seizure and in the ScPTZ model, with lesser
      neurotoxicity. Some title compounds showed lesser central nervous system
      depression compared to phenytoin. 

PMID- 24446335
TI  - The receptor-like kinases GSO1 and GSO2 together regulate root growth in
      arabidopsis through control of cell division and cell fate specification.
AB  - COVER PHOTOGRAPH: Confocal image of a median optical section through a heart
      stage Arabidopsis embryo expressing the epidermalmarker pATML1:: HTA6-GFP and
      counterstained with propidium iodide. From The receptor-like kinases GSO1 and
      GSO2 together regulate root growth in Arabidopsis through control of cell
      division and cell fate specification; Racolta et al, Developmental Dynamics
      243:257-278.

PMID- 24446336
TI  - Toxoplasma gondii rhoptry protein 38 gene: sequence variation among isolates from
      different hosts and geographical locations.
AB  - Toxoplasma gondii is an obligate intracellular parasite that is able to infect
      almost all mammalian species, and may lead to toxoplasmosis of the host. In the
      present study, we examined sequence variation in rhoptry protein 38 (ROP38) genes
      among T. gondii isolates collected from different hosts and geographical regions.
      The complete ROP38 gene from 13 T. gondii isolates was amplified and sequenced.
      The results of sequence alignments showed that the lengths of the entire ROP38
      gene ranged from 2646 to 2650 bp, with a sequence variation of 0.2-1.1%, among
      the 13 T. gondii isolates. This result indicated low sequence variation in the
      ROP38 gene. Phylogenetic analysis of ROP38 sequences using Bayesian inference
      showed that the clustering of the 13 T. gondii isolates was not consistent with
      their respective genotypes. This result indicates that the ROP38 gene is not a
      suitable genetic marker for population genetic studies of different T. gondii
      genotypes from different hosts and geographical locations, but may represent a
      potential vaccine candidate against toxoplasmosis, and hence worthy of further
      research. 

PMID- 24446337
TI  - Molecular and morphological characterization of pomegranate (Punica granatum L.)
      genotypes sampled from Coruh Valley in Turkey.
AB  - The pomegranate is one of the oldest fruits that are traditionally consumed by
      the local inhabitants of the Coruh Valley, Turkey. In this study, the molecular
      and morphological characteristics of 19 promising pomegranate genotypes selected
      from the Coruh Valley were evaluated. For the morphological evaluation, 22
      quantitative fruit characteristics were used. For the molecular evaluation, 47
      random amplified polymorphic DNA (RAPD) primers were used for polymerase chain
      reaction analysis. The principle component analysis of 22 quantitative fruit
      characteristics revealed that fruit weight and skin color are dominant traits for
      genotype discrimination. The unweighted average distance cluster of fruit
      characteristics revealed 3 distinct groups. Among the 47 RAPD primers, 9
      exhibited reliable polymorphic patterns, and generated a total of 63 RAPD bands,
      of which 49.2% were polymorphic. The similarity matrix showed that the highest
      (0.920) and lowest (0.556) genetic similarities occurred between the APS13 and
      APS28 genotypes and the APS12 and APS42 genotypes, respectively. We determined
      clear discrepancies between the morphological and molecular data; consequently,
      the differences obtained among genotypes for fruit characteristics did not
      support genetic relationships among genotypes. In conclusion, molecular data
      provided the most reliable results at the DNA level. 

PMID- 24446338
TI  - Comparative analyses of histone H3K9 trimethylations in the heart and spleen of
      normal humans.
AB  - The global features of trimethylations of histone 3 at lysine 9 (H3K9me3) have
      been well studied in recent years; however, most of these studies were performed
      in mammalian cell lines. In this study, we generated genome-wide maps of H3K9me3
      of the human heart and spleen using chromatin immunoprecipitation followed by
      high-throughput sequencing (ChIP-seq) technology. We examined the global patterns
      of H3K9me3 in both tissues and found that modifications were closely associated
      with tissue-specific expression, function, and development. In addition, we found
      that 169 genes displayed significant H3K9me3 differences between the heart and
      spleen. Among these genes, 64 were heart-H3K9me3-specific, 87 genes were spleen
      H3K9me3-specific, and 18 were shared in both heart- and spleen-H3K9me3. In
      conclusion, we observed significant differences in H3K9me3 in the heart and
      spleen, which may help to explain epigenetic differences between these tissues.
      Such novel findings highlight the significance of H3K9me3 as a potential
      biomarker or promising target for epigenetic-based disease treatment. 

PMID- 24446339
TI  - miR-34a targets the inhibin beta B gene, promoting granulosa cell apoptosis in
      the porcine ovary.
AB  - During ovarian follicular growth and development, only a few follicles actually
      ovulate. Recently, it was found that follicular atresia is triggered by granulosa
      cell apoptosis, but the molecular mechanism of follicular atresia was not
      understood. Using flow cytometry, we found that miR-34a promotes granulosa cell
      apoptosis in pig ovarian follicles. In addition, inhibin beta B was found to be a
      miR-34a target gene, based on luciferase reporter assays, quantitative RT-PCR and
      Western blotting. Taken together, our data indicate that miR-34a plays an
      important role in granulosa cell apoptosis by targeting the INHBB gene in the
      porcine ovary. 

PMID- 24446340
TI  - Correlation analysis between starch properties and single nucleotide
      polymorphisms of waxy genes in common rye (Secale cereale L.).
AB  - To understand the relationships between single nucleotide polymorphisms (SNPs) in
      the waxy gene and starch parameters in common rye, we performed sequence
      characterization, enzyme activity testing, amylopectin/amylose ratio evaluation,
      starch property testing, and correlation analysis. Specific primers were used to
      clone waxy from 20 rye cultivars. Sequence analysis showed that waxy was 2852 bp,
      including 11 exons, and sequence similarity across the 20 cultivars was over 98%.
      The Waxy protein showed >95% similarity with those from wheat, rice, and barley,
      the closest genetic relationship being with wheat Wx-A type. Waxy had multiple
      SNPs, most of which were located in the exons. Amino acid variants were found to
      be mainly distributed in the catalytic domain in an imbalanced state. Multi
      factor correlation analysis revealed significant correlation among starch pasting
      parameters in rye flour. The Waxy protein activity was significantly negatively
      correlated with the amylose content and amylopectin/amylose ratio. However,
      pasting parameters, Waxy enzyme activity, and amylopectin/amylose content ratio
      were not correlated. The correlation of SNPs, the key catalytic site of Waxy,
      with starch parameters and enzyme activity suggested that both starch pasting
      parameters and Waxy protein activity were influenced by No. 260 amino acid (aa).
      Further, the 141 and 152 aa loci were found in the enzyme-catalyzing domain of
      Waxy. Interestingly, Waxy enzyme activity was also influenced by the 363 aa locus
      in the pliable region. These results provide important theoretical regarding the
      high-throughput quality identification of noodle starch, functional studies,
      directional selection, and molecular markers of wheat Wx subunits. 

PMID- 24446341
TI  - Identification and characterization of RFRP gene in pigs and its association with
      reproductive traits.
AB  - RFamide-related peptide (RFRP) gene is a crucial gene of the hypothalamo
      pituitary-gonadal axis and plays an important role in reproduction regulation.
      This study aimed to clone and characterize the pig RFRP gene. We obtained a 645
      bp cDNA of pig RFRP gene comprising a 546-bp open reading frame, which encoded a
      peptide of 188 amino acids. The pig RFRP coding sequences have the identities of
      81, 68.8, and 76.1% with their counterparts in humans, mice, and rats,
      respectively. Real-time polymerase chain reaction showed that the pig RFRP gene
      was expressed predominantly in the stomach and testis of males, and large
      intestine and uterus of females. It was also found to be abundantly expressed in
      the cerebrum and liver tissues of both male and female pigs. The pig RFRP gene is
      4.6 kb long and contains 3 exons and 2 introns. We further identified a total of
      25 single nucleotide polymorphisms and 2 insertion/deletion (indel) polymorphisms
      across the whole RFRP gene, and 9 of them were in the exons. Marker trait
      association analysis in Yorkshire and Landrace populations showed that
      g.45859759C>T was significantly associated with the total number born of second
      parity (TBA2; P < 0.05). In conclusion, the pig RFRP gene was cloned and
      characterized in this study, and its polymorphism g.45859759C>T showed
      significant associations with reproductive traits. 

PMID- 24446342
TI  - Development of a cyclic voltammetry method for the detection of Clostridium novyi
      in black disease.
AB  - Black disease is an acute disease of sheep and cattle. The pathogen is the
      obligate anaerobe, Clostridium novyi. Due to difficulties of anaerobic culturing
      in the country or disaster sites, a simple, rapid, and sensitive method is
      required. In this study, an electrochemical method, the cyclic voltammetry
      method, basing on loop-mediated isothermal amplification (LAMP), electrochemical
      ion bonding (positive dye, methylene blue), was introduced. DNA extracted from C.
      novyi specimens was amplified through the LAMP reaction. Then the products
      combined were with methylene blue, which lead to a reduction in the oxidation
      peak current (ipA) and the reduction peak current (ipC) of the cyclic
      voltammetry. The changes of ipA/ipC were real-time measured by special designed
      electrode, so the DNA was quantitatively detected. The results displayed that
      this electrochemical detection of C. novyi could be completed in 1-2 h with the
      lowest bacterial concentration of 10(2) colony forming units/mL, and high
      accuracy (96.5%), sensitivity (96%), and specificity (97%) compared to polymerase
      chain reation. The cyclic voltammetry method was a simple and fast method, with
      high sensitivity and high specificity, and has great potential to be a usable
      molecular tool for fast diagnosis of Black disease. 

PMID- 24446343
TI  - PTGS2 gene polymorphism -765G>C is associated with coronary artery disease: a
      meta-analysis.
AB  - Previous studies focusing on the association of PTGS2 polymorphism -765G>C with
      coronary artery disease (CAD) have failed to reach the same conclusion. In the
      present study, we performed a meta-analysis to systematically summarize the
      possible association between PTGS2 polymorphism -765G>C and the risk of CAD. We
      conducted a search of case-control studies on the associations of PTGS2 with
      susceptibility to CAD in PubMed, EMBASE, and Chinese National Knowledge
      Infrastructure databases. Data from eligible studies were extracted for meta
      analysis. CAD risk associated with PTGS2 -765G>C was estimated by pooled odds
      ratios (ORs) and 95% confidence intervals (95%CI) with the RevMan 5.2 software.
      Eleven independent case-control studies on PTGS2 -765G>C were included in our
      meta-analysis. Our results showed that PTGS2 -765G>C was associated with a
      decreased risk of CAD (OR = 0.66, 95%CI = 0.56-0.79; P < 0.001). This meta
      analysis suggests that PTGS2 -765G>C is associated with a decreased risk of CAD.

PMID- 24446344
TI  - Allergenicity of an enzymatic hydrolysate of soybean 2S protein.
AB  - BACKGROUND: This study was performed to examine how the characteristics of
      soybean 2S protein influence allergenicity after enzymatic hydrolysis. Soybean 2S
      protein was extracted and enzymatic hydrolysis was performed using pepsin and
      chymotrypsin. Allergenicity was observed using soybean-sensitive patients' sera.
      RESULTS: Only 13.3% (6/45) of soybean-sensitive patients reacted to soybean
      Kunitz trypsin inhibitor (SKTI), known as the major allergen of soybean 2S
      protein. After peptic hydrolysis for 90 min at pH 1.2, the intensity of SKTI
      decreased to 25% but was still visible on SDS-PAGE. Chymotryptic hydrolysis
      following peptic hydrolysis at pH 8 for 60 min showed a limited hydrolytic effect
      on soybean 2S protein. Peptic hydrolysis of soybean 2S protein partially reduced
      the allergenicity of soybean 2S protein, while chymotryptic hydrolysis following
      peptic hydrolysis increased slightly the allergenicity. CONCLUSION: Food allergy
      caused by soybean 2S protein occurred in part of the soybean-sensitive patients.
      SKTI was partially digested after peptic hydrolysis for 90 min. The allergenicity
      was decreased with peptic hydrolysis, while subsequent treatment of chymotrypsin
      increased slightly the allergenicity.

PMID- 24446345
TI  - Rational design of substrate-based multivalent inhibitors of the histone
      acetyltransferase Tip60.
AB  - Tip60, the 60 kDa HIV-1 Tat-interactive protein, is a key member of the MYST
      family of histone acetyltransferases (HATs) and plays critical roles in apoptosis
      and DNA repair. Potent and selective inhibitors of Tip60 are valuable tools for
      studying the functions of this potential drug target. In this work, we designed,
      synthesized and evaluated a new set of substrate-based inhibitors containing
      multiple binding modalities. In addition to the coenzyme A (CoA) moiety and the
      histone H3 peptide backbone, mono- and tri-methyl marks were incorporated at Lys
      4 and/or Lys 9 sites in the H3 peptide substrate. The biochemical assay results
      showed that the presence of methyl group(s) on the substrate resulted in more
      potent inhibitors of Tip60, relative to the parent H3-CoA bisubstrate inhibitor.
      Importantly, by comparing the inhibitory properties of the ligands against full
      length Tip60 and the HAT domain, we determined that the K4me1 and K9me3 marks
      contributed to the potency augmentation by interacting with the catalytic region
      of the enzyme. 

PMID- 24446346
TI  - Early stage of obesity potentiates nitric oxide reduction during the development
      of renal failure.
AB  - BACKGROUND: Obesity is a serious health problem associated with the pathogenesis
      of various metabolic diseases. Nitric Oxide (NO) plays an important role in
      kidney function and altered NO levels have been associated with the pathogenesis
      of obesity. Therefore, we aimed to study whether an early stage of obesity
      contributes with progression of renal failure through further NO impairment.
      METHODS: Male C57BL/6 mice were fed with a high-fat diet (HFD) or a normal diet
      (ND) during 2 weeks. All mice underwent either sham surgery (sham) or 5/6
      nephrectomy (Np). One group of HFD Np mice was treated with antioxidants plus L
      arginine. Kidney damage parameters were assessed and eNOS metabolism was
      evaluated. RESULTS: Mice on a HFD increased body weight, eNOS protein and mRNA
      expression, and radical oxygen species (ROS). Urine nitrites excretion, urine
      volume, and plasma BH4 were decreased. In HFD mice, 5/6 Np further increased BH2
      and urine protein concentration, ROS levels, and eNOS mRNA expression. The
      decrease in BH4 plasma levels and urine nitrites excretion was accentuated. NO
      synthesis stimulation with the antioxidants + L-arginine treatment prevented all
      these changes. CONCLUSIONS: The early changes in NO metabolism are associated
      with an early stage of obesity. This effect on NO potentiates kidney damage
      development.

PMID- 24446347
TI  - Relationships of clinic size, geographic region, and race/ethnicity to the
      frequency of missed/shortened dialysis treatments.
AB  - BACKGROUND: Significant international differences abound in the adherence of
      hemodialysis (HD) patients to prescribed treatments. Unfortunately, factors
      influencing adherence within the United States (US) are not well understood. This
      study explores the hypothesis that race/ethnicity, geographic region and clinic
      size are associated with differences in the frequency of missed/shortened
      treatments. METHODS: A retrospective analysis on all prevalent chronic HD
      patients treated at Dialysis Clinics Inc. facilities between January 2007 and
      June 2008. Logistic regression models were computed in which the outcome measures
      were the odds for missing or shortening treatments. RESULTS: The cohort consisted
      of 15,340 HD patients of whom 48% were non-Hispanic whites (NHW), 41% African
      Americans (AA), 6% Hispanics, 2% Native Americans, 2% Asians, and 1% unknown.
      Patients were older in the Northeast than in the South (p < 0.001) or West (p =
      0.0052). The frequency of missed and shortened treatments was lower in the
      Northeast than other regions, p < 0.0001. Hospitalization rates were lower in the
      West than the Northeast (p < 0.01) but mortality rates were similar across all
      regions. The odds ratio and 95% confidence interval for missed [1.31 (1.14-1.52)]
      and shortened treatments [1.86 (1.73-2.0)] were greater in clinics with >100
      patients than in those with <50 patients. Compared to NHW, the frequencies of
      missed and shortened treatments were higher in AA, Hispanics and Native Americans
      (p < 0.001) but lower among Asians (p < 0.001). CONCLUSION: The frequency of
      missed and shortened HD varies significantly by race/ethnicity, geographic region
      and clinic size. The relationship of clinic size to missed/shortened treatments
      may warrant consideration when planning new HD facilities.

PMID- 24446348
TI  - Accuracy of the estimation of glomerular filtration rate within a population of
      critically ill patients.
AB  - BACKGROUND: Accuracy of glomerular filtration rate (GFR) estimates has been
      questioned and several authors recommend routine use of measured renal creatinine
      clearance (CLCR) as a surrogate of GFR in the intensive care unit (ICU). Our
      purpose was to compare estimates of GFR using Cockroft-Gault (CG), Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal
      Disease Study (MDRD) equations with 8h-CLCR, within a population of critically
      ill patients with a wide range of measured CLCR. METHODS: Through a prospective,
      observational study of 54 patients with normal serum creatinine (sCr) admitted to
      ICU, daily 8h-CLCR (reference method) and GFR estimates (644 paired samples) were
      matched and compared. Augmented renal clearance (ARC) was defined as 8h-CLCR >130
      ml/min/1.73 m(2). RESULTS: No significant difference was found between mean 8h
      CLCR (135.5 ml/min/1.73 m(2)) and CG equation (135.7 ml/min/1.73 m(2)), but
      significant differences (p < 0.01) were found for the MDRD (124.4 ml/min/1.73
      m(2)) and CKD-EPI (107.6 ml/min/1.73 m(2)) equations. Correlation between 8h-CLCR
      and all estimates was weak (R = 0.2, 0.19 and 0.34, respectively). We observed
      poor agreement in terms of precision (40.9, 39.8 and 33.4%, respectively).
      Analysing subgroups, we observed that all equations significantly underestimated
      8h-CLCR >120 ml/min/1.73 m(2) and overestimated 8h-CLCR <120 ml/min/1.73 m(2) (p
      < 0.05). The incidence of ARC patients was 55.6%. CONCLUSIONS: Estimates of GFR
      using CG, CKD-EPI and MDRD formulae are flawed in the critically ill with normal
      sCr, significantly underestimating renal function in those with ARC and
      overestimating it in those with normal or decreased 8h-CLCR. Globally, the
      population exhibited ARC on more than half of the ICU admission days.

PMID- 24446349
TI  - Chronic kidney disease and the aging population.

PMID- 24446350
TI  - Photoresponsive hybrid raspberry-like colloids based on cucurbit[8]uril host
      guest interactions.
AB  - Hybrid raspberry-like colloids (HRCs) were prepared by employing cucurbit[8]uril
      (CB[8]) as a supramolecular linker to assemble functional polymeric nanoparticles
      onto a silica core. The formed HRCs are photoresponsive and can be reversibly
      disassembled upon light irradiation. This facile supramolecular approach provides
      a platform for the synthesis of colloids with sophisticated structures and
      properties. 

PMID- 24446351
TI  - MicroRNA-190 regulates hypoxic pulmonary vasoconstriction by targeting a voltage
      gated K+ channel in arterial smooth muscle cells.
AB  - Pulmonary arterial hypertension (PAH) is associated with sustained
      vasoconstriction, profound structural remodeling of vasculatures and alterations
      in Ca(2+) homeostasis in arterial smooth muscle cells (SMCs), while the
      underlying mechanisms are still elusive. By regulating the expression of
      proteins, microRNAs (miRNAs) are known to play an important role in cell fates
      including differentiation, apoptosis and proliferation, and may be involved in
      the development of PAH. Based on our previous study, hypoxia produced a
      significant increase of the miR-190 level in the pulmonary artery (PA), here, we
      used synthetic miR-190 to mimic the increase in hypoxic conditions and showed
      evidence for the effects of miR-190 on pulmonary arterial vasoconstriction and
      Ca(2+) influx in arterial SMCs. Synthetic miR-190 remarkably enhanced the
      vasoconstriction responses to phenylephrine (PE) and KCl. The voltage-gated K(+)
      channel subfamily member, Kcnq5, mRNA was shown to be a target for miR-190.
      Meanwhile, miR-190 antisense oligos can partially reverse the effects of miR-190
      on PASMCs and PAs. Therefore, these results suggest that miR-190 appears to be a
      positive regulator of Ca(2+) influx, and plays an important role in hypoxic
      pulmonary vascular constriction.

PMID- 24446352
TI  - Immunohistochemical detection of GnRH-like peptides in the neural ganglia and
      testis of Haliotis asinina.
AB  - Gonadotropin releasing hormone (GnRH) is a peptide that is conserved in both
      vertebrate and invertebrate species. In this study, we have demonstrated the
      distribution pattern of two isoforms of GnRH-like peptides in the neural ganglia
      and testis of reproductively mature male abalone, H. asinina, by
      immunohistochemistry and whole mount immunofluorescence. We found octopus (oct)
      GnRH and tunicate-I (t) GnRH-I immunoreactivities (ir) in type 1 neurosecretory
      cells (NS1) and they were expressed mostly within the ventral horn of the
      cerebral ganglion, whereas in pleuropedal ganglia they were localized primarily
      in the dorsal horn. Furthermore, tGnRH-I-ir were strongly detected in fibers at
      the caudal part of the cerebral ganglia and both ventral and dorsal horns of the
      pleuropedal ganglia. In the testis, only octGnRH-ir was found primarily in the
      granulated cell and central capillaries within the trabeculae. These results
      suggest that multiple GnRH-like peptides are present in the neural ganglia which
      could be the principal source of their production, whereas GnRH may also be
      synthesized locally in the testis and act as the paracrine control of testicular
      maturation.

PMID- 24446353
TI  - Ontogeny of mouthpart sensilla of Muga silkworm: a scanning electron microscopic
      study.
AB  - Scanning electron microscopy on the postembryonic development of the mouthpart
      sensory structures of the Muga silk moth, Antheraea assamensis revealed the
      presence of a variety of sensilla. The types, distribution pattern of the
      sensilla remained almost the same in the different larval stages except for the
      number and dimension in some cases. The findings of the study assumes
      significance because the silk moth, Antheraea assamensis is a species endemic to
      the North Eastern part of India and very few reports are available on it. In
      fact, the present study provides the first report on the ontogeny of the mouth
      part sensilla of the silk moth species. Since mouth part sensilla and their
      surface micro structural characteristics are extremely important in understanding
      their roles in searching behavior during feeding, the present study will
      certainly help in developing strategies for proper rearing of this economically
      important insect species.

PMID- 24446354
TI  - Loss of sulfur dioxide and changes in some chemical properties of Malatya
      apricots (Prunus armeniaca L.) during sulfuring and drying.
AB  - BACKGROUND: This study was conducted to determine the differences in some
      analytical properties of four apricot cultivars and to determine the changes in
      these analytical properties during sulfuring and sun-drying. RESULTS: There were
      significant differences in the contents of polyphenols, carotenoids and organic
      acids (OA) as well as antioxidant activities (AOAs) of the cultivars (P < 0.05).
      After sulfuring and drying, considerable reductions were detected in the contents
      of total polyphenols (TPCs, 11-26%), OAs (4-32%) and beta-carotene (6-21%), and
      AOAs (2-21%) of the samples. Sun-drying resulted in 71-83% decreases in sulfur
      dioxide (SO2 ) contents of sulfured-dried apricots (SDAs) in comparison with
      apricots immediately after sulfuring. As the TPCs increased, the SO2 absorption
      by the samples also increased. In contrast, the OA contents had no effect on SO2
      absorption, but an increase in OA content resulted in an increase in the browning
      values of the SDAs. As expected, increases in contents of ferulic acid (r =
      0.932), chlorogenic acid (r = 0.850), epicatechin (r = 0.804) and quercetin (r =
      0.750) led to an increase in browning values of the SDAs. CONCLUSION: There were
      significant effects of cultivar and processing on the physico-chemical properties
      investigated in the study, and with the absorption of SO2 and the formation of a
      brown colour in the samples.

PMID- 24446355
TI  - Protein folding simulations by generalized-ensemble algorithms.
AB  - In the protein folding problem, conventional simulations in physical statistical
      mechanical ensembles, such as the canonical ensemble with fixed temperature, face
      a great difficulty. This is because there exist a huge number of local-minimum
      energy states in the system and the conventional simulations tend to get trapped
      in these states, giving wrong results. Generalized-ensemble algorithms are based
      on artificial unphysical ensembles and overcome the above difficulty by
      performing random walks in potential energy, volume, and other physical
      quantities or their corresponding conjugate parameters such as temperature,
      pressure, etc. The advantage of generalized-ensemble simulations lies in the fact
      that they not only avoid getting trapped in states of energy local minima but
      also allows the calculations of physical quantities as functions of temperature
      or other parameters from a single simulation run. In this article we review the
      generalized-ensemble algorithms. Four examples, multicanonical algorithm, replica
      exchange method, replica-exchange multicanonical algorithm, and multicanonical
      replica-exchange method, are described in detail. Examples of their applications
      to the protein folding problem are presented. 

PMID- 24446356
TI  - Application of Markov State Models to simulate long timescale dynamics of
      biological macromolecules.
AB  - Conformational changes of proteins are an*Author contributed equally with all
      other contributors. essential part of many biological processes such as: protein
      folding, ligand binding, signal transduction, allostery, and enzymatic catalysis.
      Molecular dynamics (MD) simulations can describe the dynamics of molecules at
      atomic detail, therefore providing a much higher temporal and spatial resolution
      than most experimental techniques. Although MD simulations have been widely
      applied to study protein dynamics, the timescales accessible by conventional MD
      methods are usually limited to timescales that are orders of magnitude shorter
      than the conformational changes relevant for most biological functions. During
      the past decades great effort has been devoted to the development of theoretical
      methods that may enhance the conformational sampling. In recent years, it has
      been shown that the statistical mechanics framework provided by discrete-state
      and -time Markov State Models (MSMs) can predict long timescale dynamics from a
      pool of short MD simulations. In this chapter we provide the readers an account
      of the basic theory and selected applications of MSMs. We will first introduce
      the general concepts behind MSMs, and then describe the existing procedures for
      the construction of MSMs. This will be followed by the discussions of the
      challenges of constructing and validating MSMs, Finally, we will employ two
      biologically-relevant systems, the RNA polymerase and the LAO-protein, to
      illustrate the application of Markov State Models to elucidate the molecular
      mechanisms of complex conformational changes at biologically relevant timescales.

PMID- 24446357
TI  - Understanding protein dynamics using conformational ensembles.
AB  - Conformational ensembles are powerful tools to represent the range of
      conformations that can be sampled by proteins. They can be generated by using
      purely theoretical methods or, as is most often the case, by fitting ensembles of
      conformations to experimental data that report on the amplitude of protein
      dynamics. Conformational ensembles have been useful instruments to study
      fundamental properties of proteins such as the mechanism of molecular
      recognition, the early stages of protein folding and the mechanism by which
      structural information propagates through the structures of globular proteins
      structures via correlated backbone motions. In this chapter I will review the
      various approaches that have been put forward in the literature to generate
      conformation ensembles for proteins and present a selection of examples of how
      such representations of the structural heterogeneity of proteins have been used
      to explore the fundamental properties of these macromolecules. Finally, I will
      look ahead at likely future developments in this area, which is important for
      structural and chemical biology as well as for biophysics. 

PMID- 24446358
TI  - Generative models of conformational dynamics.
AB  - Atomistic simulations of the conformational dynamics of proteins can be performed
      using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three
      dimensional structures produced during simulation can be analyzed in a number of
      ways to elucidate the thermodynamic and kinetic properties of the system. The
      goal of this chapter is to review both traditional and emerging methods for
      learning generative models from atomistic simulation data. Here, the term
      'generative' refers to a model of the joint probability distribution over the
      behaviors of the constituent atoms. In the context of molecular modeling,
      generative models reveal the correlation structure between the atoms, and may be
      used to predict how the system will respond to structural perturbations. We begin
      by discussing traditional methods, which produce multivariate Gaussian models. We
      then discuss GAMELAN (GRAPHICAL MODELS OF ENERGY LANDSCAPES), which produces
      generative models of complex, non-Gaussian conformational dynamics (e.g.,
      allostery, binding, folding, etc.) from long timescale simulation data. 

PMID- 24446359
TI  - Generalized spring tensor models for protein fluctuation dynamics and
      conformation changes.
AB  - BACKGROUND: In the last decade, various coarse-grained elastic network models
      have been developed to study the large-scale motions of proteins and protein
      complexes where computer simulations using detailed all-atom models are not
      feasible. Among these models, the Gaussian Network Model (GNM) and Anisotropic
      Network Model (ANM) have been widely used. Both models have strengths and
      limitations. GNM can predict the relative magnitudes of protein fluctuations
      well, but due to its isotropy assumption, it cannot be applied to predict the
      directions of the fluctuations. In contrast, ANM adds the ability to do the
      latter, but loses a significant amount of precision in the prediction of the
      magnitudes. RESULTS: In this book chapter, we present a single model, called
      generalized spring tensor model (STeM), that is able to predict well both the
      magnitudes and the directions of the fluctuations. Specifically, STeM performs
      equally well in B-factor predictions as GNM and has the ability to predict the
      directions of fluctuations as ANM. This is achieved by employing a physically
      more realistic potential, the Go-like potential. The potential, which is more
      sophisticated than that of either GNM or ANM, though adds complexity to the
      derivation process of the Hessian matrix (which fortunately has been done once
      for all and the MATLAB code is freely available electronically at
      http://www.cs.iastate.edu/~gsong/STeM ), causes virtually no performance
      slowdown. In addition, we show that STeM can be further extended to an all-atom
      model and protein fluctuation dynamics computed by all-atom STeM matches closely
      with that by Normal Mode Analysis (NMA). CONCLUSIONS: Derived from a physically
      more realistic potential, STeM proves to be a natural solution in which
      advantages that used to exist in two separate models, namely GNM and ANM, are
      achieved in one single model. It thus lightens the burden to work with two
      separate models and to relate the modes of GNM with those of ANM at times. By
      examining the contributions of different interaction terms in the Go potential to
      the fluctuation dynamics, STeM reveals, (i) a physical explanation for why the
      distance-dependent, inverse distance square (i.e., 1/r (2)) spring constants
      perform better than the uniform ones, and (ii), the importance of three-body and
      four-body interactions to properly modeling protein dynamics.STeM is not limited
      to coarse-grained protein models that use a single bead, usually the alpha
      carbon, to represent each residue. The core idea of STeM, deriving the Hessian
      matrix directly from a physically realistic potential, can be extended to all
      atom models as well. We did this and discovered that all-atom STeM model
      represents a highly close approximation of NMA, yet without the need for energy
      minimization.

PMID- 24446360
TI  - The joys and perils of flexible fitting.
AB  - While performing their functions, biological macromolecules often form large,
      dynamically changing macromolecular assemblies. Only a relatively small number of
      such assemblies have been accessible to the atomic-resolution techniques X-ray
      crystallography and NMR. Electron microscopy in conjunction with image
      reconstruction has become the preferred alternative for revealing the structures
      of such macromolecular complexes. However, for most assemblies the achievable
      resolution is too low to allow accurate atomic modeling directly from the data.
      Yet, useful models often can be obtained by fitting atomic models of individual
      components into a low-resolution reconstruction of the entire assembly. Several
      algorithms for achieving optimal fits in this context were developed recently,
      many allowing considerable degrees of flexibility to account for binding-induced
      conformational changes of the assembly components. This chapter describes the
      advantages and potential pitfalls of these methods and puts them into perspective
      with alternative approaches such as iterative modular fitting of rigid-body
      domains. 

PMID- 24446361
TI  - Coarse-grained models of the proteins backbone conformational dynamics.
AB  - Coarse-grained models are more and more frequently used in the studies of the
      proteins structural and dynamic properties, since the reduced number of degrees
      of freedom allows to enhance the conformational space exploration. This chapter
      attempts to provide an overview of the various coarse-grained models that were
      applied to study the functional conformational changes of the polypeptides main
      chain around their native state. It will more specifically discuss the methods
      used to represent the protein backbone flexibility and to account for the physico
      chemical interactions that stabilize the secondary structure elements.

PMID- 24446362
TI  - Simulating protein folding in different environmental conditions.
AB  - Molecular dynamics simulations have become an invaluable tool in investigating
      the dynamics of protein folding. However, most computational studies of protein
      folding assume dilute aqueous simulation conditions in order to reduce the
      complexity of the system under study and enhance the efficiency. Nowadays, it is
      evident that environmental conditions encountered in vivo (or even in vitro) play
      a major role in regulating the dynamics of protein folding especially when one
      considers the highly condensed environment in the cellular cytoplasm. In order to
      factor in these conditions, we can utilize the high efficiency of well-designed
      low resolution (coarse-grained) simulation models to reduce the complexity of
      these added protein-milieu interactions involving different time and length
      scales. The goal of this chapter is to describe some recently developed coarse
      grained simulation techniques that are specifically designed to go beyond
      traditional aqueous solvent conditions. The chapter also gives the reader a
      flavor of the things that we can study using such "smart" low resolution models. 

PMID- 24446363
TI  - Simulating the peptide folding kinetic related spectra based on the Markov State
      Model.
AB  - Optical spectroscopic tools are used to monitor protein folding/unfolding
      dynamics after a fast triggering such as the laser induced temperature jump.
      These techniques provide new opportunities for comparison between theory and
      simulations and atom-level understanding protein folding mechanism. However, the
      direct comparison still face two main challenges: a gap between folding relevant
      timescales (microseconds or above) and length of molecular dynamics simulations
      (typically tens to hundreds of nanoseconds), and difficulty in directly
      calculating spectroscopic observables from simulation configurations. Markov
      State Model (MSM) approach is one of the most powerful means which can increase
      simulations timescale up to microsecond or even millisecond. We address progress
      on modeling infrared and fluorescence spectroscopic signals of temperature jump
      induced unfolding dynamics for a few small proteins. The harmoniousness between
      experiment and theoretical can both improve our understanding of protein folding
      mechanisms and provide direct validation of those theoretical models. 

PMID- 24446364
TI  - The dilemma of conformational dynamics in enzyme catalysis: perspectives from
      theory and experiment.
AB  - The role of protein dynamics in catalysis is a contemporary issue that has
      stirred intense debate in the field. This chapter provides a brief overview of
      the approaches and findings of a wide range of experimental, computational and
      theoretical studies that have addressed this issue. We summarize the results of
      our recent atomistic molecular dynamic studies on cis-trans isomerase. Our
      results help to reconcile the disparate perspectives regarding the complex role
      of enzyme dynamics in the catalytic step and emphasize the major contribution of
      transition state stabilization in rate enhancement. 

PMID- 24446365
TI  - Exploiting protein intrinsic flexibility in drug design.
AB  - Molecular recognition in biological systems relies on the existence of specific
      attractive interactions between two partner molecules. Structure-based drug
      design seeks to identify and optimize such interactions between ligands and their
      protein targets. The approach followed in medicinal chemistry follows a
      combination of careful analysis of structural data together with experimental
      and/or theoretical studies on the system. This chapter focuses on the fact that a
      protein is not fully characterized by a single structure, but by an ensemble of
      states, some of them represent "hidden conformations" with cryptic binding sites.
      We highlight case studies where both experimental and computational methods have
      been used to mutually drive each other in an attempt to improve the success of
      the drug design approaches.Advances in both experimental techniques and
      computational methods have greatly improved our physico-chemical understanding of
      the functional mechanisms in biomolecules and opened a debate about the interplay
      between molecular structure and biomolecular function. The beautiful static
      pictures of protein structures may have led to neglecting the intrinsic protein
      flexibility, however we are entering a new era where more sophisticated methods
      are used to exploit this ability of macromolecules, and this will definitely lead
      to the inclusion of the notion in the pharmaceutical field of drug design. 

PMID- 24446366
TI  - NMR and computational methods in the structural and dynamic characterization of
      ligand-receptor interactions.
AB  - The recurrent failures in drug discovery campaigns, the asymmetry between the
      enormous financial investments and the relatively scarce results have fostered
      the development of strategies based on complementary methods. In this context in
      recent years the rigid lock-and-key binding concept had to be revisited in favour
      of a dynamic model of molecular recognition accounting for conformational changes
      of both the ligand and the receptor. The high level of complexity required by a
      dynamic description of the processes underlying molecular recognition requires a
      multidisciplinary investigation approach. In this perspective, the combination of
      nuclear magnetic resonance spectroscopy with molecular docking, conformational
      searches along with molecular dynamics simulations has given new insights into
      the dynamic mechanisms governing ligand receptor interactions, thus giving an
      enormous contribution to the identification and design of new and effective
      drugs. Herein a succinct overview on the applications of both NMR and
      computational methods to the structural and dynamic characterization of ligand
      receptor interactions will be presented. 

PMID- 24446367
TI  - Molecular dynamics simulation of membrane proteins.
AB  - Membrane proteins play crucial roles in a range of biological processes. High
      resolution structures provide insights into the functional mechanisms of membrane
      proteins, but detailed biophysical characterization of membrane proteins is
      difficult. Complementary to experimental techniques, molecular dynamics
      simulations is a powerful tool in providing more complete description of the
      dynamics and energetics of membrane proteins with high spatial-temporal
      resolution. In this chapter, we provide a survey of the current methods and
      technique issues for setting up and running simulations of membrane proteins. The
      recent progress in applying simulations to understanding various biophysical
      properties of membrane proteins is outlined. 

PMID- 24446368
TI  - Free-energy landscape of intrinsically disordered proteins investigated by all
      atom multicanonical molecular dynamics.
AB  - We introduce computational studies on intrinsically disordered proteins (IDPs).
      Especially, we present our multicanonical molecular dynamics (McMD) simulations
      of two IDP-partner systems: NRSF-mSin3 and pKID-KIX. McMD is one of enhanced
      conformational sampling methods useful for conformational sampling of
      biomolecular systems. IDP adopts a specific tertiary structure upon binding to
      its partner molecule, although it is unstructured in the unbound state (i.e. the
      free state). This IDP-specific property is called "coupled folding and binding".
      The McMD simulation treats the biomolecules with an all-atom model immersed in an
      explicit solvent. In the initial configuration of simulation, IDP and its partner
      molecules are set to be distant from each other, and the IDP conformation is
      disordered. The computationally obtained free-energy landscape for coupled
      folding and binding has shown that native- and non-native-complex clusters
      distribute complicatedly in the conformational space. The all-atom simulation
      suggests that both of induced-folding and population-selection are coupled
      complicatedly in the coupled folding and binding. Further analyses have
      exemplified that the conformational fluctuations (dynamical flexibility) in the
      bound and unbound states are essentially important to characterize IDP
      functioning. 

PMID- 24446369
TI  - Coordination and control inside simple biomolecular machines.
AB  - Biomolecular machines can achieve physiological functions precisely and
      efficiently, though they always operate under fluctuations and noises. We review
      two types of simple machinery that we have recently studied. The machinery can be
      regarded as molecular motors. They transform chemical free energy from NTP
      hydrolysis to mechanical work. One type belongs to small monomeric helicases that
      move directionally along single-stranded nucleic acid, and may further unwind the
      duplex part for gene replication or repair. The other type belongs to ring-shaped
      NTPase motors that also move or transport nucleic acid or protein substrate in a
      directional manner, such as for genome packaging or protein degradation. The
      central issue in this review is on how the machinery coordinates essential
      degrees of freedom during the mechanochemical coupling process. Further concerns
      include how the coordination and control are manifested in experiments, and how
      they can be captured well in modeling and computational research. We employed
      atomistic molecular dynamics simulations, coarse-grained analyses, and stochastic
      modeling techniques to examine the molecular machines at multiple resolutions and
      timescales. Detailed descriptions on how the protein interacts with its substrate
      at interface, as well as how multiple protein subunits are coordinated are
      summarized. 

PMID- 24446370
TI  - Multi-state targeting machinery govern the fidelity and efficiency of protein
      localization.
AB  - Proper localization of newly synthesized proteins is essential to cellular
      function. Among different protein localization modes, the signal recognition
      particle (SRP) and SRP receptor (SR) constitute the conserved targeting machinery
      in all three life kingdoms and mediate about one third of the protein targeting
      reactions. Based on experimental and computational studies, a detailed molecular
      model is proposed to explain how this molecular machinery governs the efficiency
      and fidelity of protein localizations. In this targeting machinery, two distinct
      SRP GTPases are contained into the SRP and SR that are responsible to the
      interactions between SRP and SR. These two GTPases can interact with one another
      through a series of sequential and discrete interaction states that are the early
      intermediate formation, stable complex association, and GTPase activation. In
      contrast to canonical GTPases, a floppy and open conformation adopted in free SRP
      GTPases can facilitate efficient GTP/GDP exchange without the aid of any external
      factors. As the apo-form free SRP GTPases can adopt the conformational states of
      GDP- or GTP-bound form, the binding of GTP/GDP follows a mechanism of
      conformational selection. In the first step of complex formation, the two SRP
      GTPases can rapidly assemble into an unstable early intermediate by selecting and
      stabilizing one another's primed states from the equilibrium conformational
      ensemble. Subsequently, extensive inter- and intra-domain changes rearrange the
      early complex into a tight and closed state of stable complex through induced fit
      mechanism. Upon stable complex association, further tune of several important
      interaction networks activates the SRP GTPase for GTP hydrolysis. These different
      conformational states are coupled to corresponding protein targeting events, in
      which the complex formation deliveries the translating ribosome to the target
      membrane and the GTPase activation couples to the cargo release from SRP-SR
      machinery to the translocation channel. It is thus suggested that the SRP GTPases
      constitute a self-sufficient system to execute exquisite spatial and temporal
      control of the complex targeting process. The working mechanism of the SRP and SR
      provides a novel paradigm of how the protein machinery functions in controlling
      diverse biological processes efficiently and faithfully. 

PMID- 24446371
TI  - Molecular dynamics simulations of F1-ATPase.
AB  - F1-ATPase is a rotary motor enzyme. Despite many theoretical and experimental
      studies, the molecular mechanism of the motor rotation is still not fully
      understood. However, plenty of available data provide a clue as to how this
      molecular motor rotates: with nucleotide perturbations, the catalytically active
      beta subunit propagates its structural changes to the entire alpha3beta3 complex
      via both sides of the subunits, resulting that asymmetry is created in the
      alpha3beta3 hexamer ring. In the sequential reaction step, the structure of the
      asymmetrical alpha3beta3 complex changes from one state to the other due to the
      nucleotide perturbations, and the gamma subunit axis follows the sequentially
      changing alpha3beta3 structure. Therefore, there are mainly two essential
      elements for motor rotation: the conformational change of the beta subunit and
      the asymmetrical structure of the alpha3beta3 subunit complex. Therefore, this
      chapter reports a series of studies focused on these two elements via
      combinational approaches of molecular dynamics (MD) simulations and experimental
      or other theoretical studies. In addition to the motor rotation factors, the
      combined study also revealed other important elements of F1-ATPase, such as
      torque transmission and the chemical reaction pathway, which is described in the
      later part of this chapter. All of these results provide insight into the
      rotational mechanism and deepen the understanding of this molecular motor. 

PMID- 24446372
TI  - Chemosensorial G-proteins-coupled receptors: a perspective from computational
      methods.
AB  - G-protein coupled receptors (GPCRs) constitute the targets of about 40 % of all
      the pharmaceutical drugs in the market and, among other functions, a large
      portion of the family detects odorants and a variety of tastant molecules.
      Computational techniques are instrumental to understand structure, dynamics and
      function of the cascades triggered by these receptors. As an example, here we
      report our own computational work aimed to dissect GPCR molecular mechanisms for
      chemical senses. The implications of our work for systems biology and for
      pharmacology are discussed. 

PMID- 24446373
TI  - Discovery of heterocyclic nonacetamide synaptic vesicle protein 2A (SV2A) ligands
      with single-digit nanomolar potency: opening avenues towards the first SV2A
      positron emission tomography (PET) ligands.
AB  - The role of the synaptic vesicle protein 2A (SV2A) protein, target of the
      antiepileptic drug levetiracetam, is still mostly unknown. Considering its
      potential to provide in vivo functional insights into the role of SV2A in
      epileptic patients, the development of an SV2A positron emission tomography (PET)
      tracer has been undertaken. Using a 3D pharmacophore model based on close
      analogues of levetiracetam, we report the rationale design of three heterocyclic
      non-acetamide lead compounds, UCB-A, UCB-H and UCB-J, the first single-digit
      nanomolar SV2A ligands with suitable properties for development as PET tracers.

PMID- 24446374
TI  - Vinculin regulates assembly of talin: beta3 integrin complexes.
AB  - Vinculin is a talin-binding protein that promotes integrin-mediated cell
      adhesion, but the mechanisms are not understood. Because talin is a direct
      activator of integrins, we asked whether and how vinculin regulates the formation
      of integrin: talin complexes. We report that VD1 (aa 1-258) and its talin-binding
      mutant, VD1A50I, bind directly and equally to several beta integrin cytoplasmic
      tails (betaCT). Results from competition assays show that VD1, but not VD1A50I,
      inhibits the interaction of talin (Tn) and talin rod (TnR), but not talin head
      (TnH) with beta3CT. The inhibition observed could be the result of VD1 binding to
      one or more of the 11 vinculin binding sites (VBSs) in the TnR domain. Our
      studies demonstrate that VD1 binding to amino acids 482-911, a VBS rich region,
      in TnR perturbs the interaction of rod with beta3CT. The integrin activation
      assays done using CHOA5 cells show that activated vinculin enhances alphaIIbbeta3
      integrin activation and that the effect is dependent on talin. The TnR domain
      however shows no integrin activation unlike TnH that shows enhanced integrin
      activation. The overall results indicate that activated vinculin promotes talin
      mediated integrin activation by binding to accessible VBSs in TnR and thus
      displacing the TnR from the beta3 subunit. The study presented, defines a novel
      direct interaction of VD1 with beta3CT and provides an attractive explanation for
      vinculin's ability to potentiate integrin-mediated cell adhesion through directly
      binding to both TnR and the integrin cytoplasmic tail.

PMID- 24446375
TI  - Purification, characterization and partial sequence of a pro-inflammatory lectin
      from seeds of Canavalia oxyphylla Standl. & L. O. Williams.
AB  - Recent studies have shown that lectins are promising tools for use in various
      biotechnological processes, as well as studies of various pathological
      mechanisms, isolation, and characterization of glycoconjugates and understanding
      the mechanisms underlying pathological mechanisms conditions, including the
      inflammatory response. This study aimed to purify, characterize
      physicochemically, and predict the biological activity of Canavalia oxyphylla
      lectin (CoxyL) in vitro and in vivo. CoxyL was purified by a single-step affinity
      chromatography in Sephadex(r) G-50 column. Sodium dodecyl sulfate polyacrylamide
      gel electrophoresis showed that the pure lectin consists of a major band of 30
      kDa (alpha-chain) and two minor components (beta-chain and gamma-chain) of 16 and
      13 kDa, respectively. These data were further confirmed by electrospray
      ionization mass spectrometry, suggesting that CoxyL is a typical ConA-like
      lectin. In comparison with the average molecular mass of alpha-chain, the partial
      amino acid sequence obtained corresponds to approximately 45% of the total CoxyL
      sequence. CoxyL presented hemagglutinating activity that was specifically
      inhibited by monosaccharides (D-glucose, D-mannose, and alpha-methyl-D-mannoside)
      and glycoproteins (ovalbumin and fetuin). Moreover, CoxyL was shown to be
      thermostable, exhibiting full hemagglutinating activity up to 60 degrees C, and
      it was pH-sensitive for 1 h, exhibiting maximal activity at pH 7.0. CoxyL caused
      toxicity to Artemia nauplii and induced paw edema in rats. This biological
      activity highlights the importance of lectins as important tools to better
      understand the mechanisms underlying inflammatory responses.

PMID- 24446376
TI  - Binding of azurin to cytochrome c 551 as investigated by surface plasmon
      resonance and fluorescence.
AB  - The interaction between azurin (Az) and cytochrome c 551 (CytC551) from
      Pseudomonas aeruginosa deserves particular interest for both its physiological
      aspects and their possible applications in bionano devices. Here, the kinetics of
      the interaction has been studied by surface plasmon resonance and fluorescence
      quenching. Surface plasmon resonance data have been successfully interpreted by
      the heterogeneous ligand model, which predicts the existence of two binding sites
      on the immobilized Az for CytC551 molecules in solution. On the other hand, the
      fluorescence study indicates the formation of a complex, with the involvement of
      the lone Az tryptophan (Trp) at position 48. The two different techniques point
      out the occurrence of an encounter complex between Az and CytC551 that evolves
      toward the formation of a more stable complex characterized by an equilibrium
      dissociation constant KD typical of transient interactions.

PMID- 24446377
TI  - Spectroscopic studies on the interaction mechanisms of safranin T with herring
      sperm DNA using acridine orange as a fluorescence probe.
AB  - Under the condition of physiological pH environment (pH = 7.40), the interactions
      of safranin T (ST) with herring sperm DNA were studied by means of spectral
      methods using acridine orange (AO) as a fluorescence probe. The spectroscopic
      characteristics of DNA-AO in the case of ST (along with the increase of
      concentration) were observed in an aqueous medium. The binding constants for ST
      stranded DNA and competitive bindings of ST interacting with DNA-AO systems were
      examined by fluorescence spectra, and the binding mechanism of ST with DNA was
      researched via viscosity measurements. All the testimony manifested that bonding
      modes between ST and DNA were evidenced to be intercalative binding and
      electrostatic binding, and the combining constant of ST with DNA was obtained.
      The binding of ST to DNA was driven by entropy and enthalpy through the
      calculated thermodynamic parameters (Deltar Hm (?), Deltar Sm and Deltar Gm (?)).

PMID- 24446378
TI  - Molecular dynamics simulation studies for DNA sequence recognition by reactive
      metabolites of anticancer compounds.
AB  - The discovery of novel anticancer molecules 5F-203 (NSC703786) and 5-aminoflavone
      (5-AMF, NSC686288) has addressed the issues of toxicity and reduced efficacy by
      targeting over expressed Cytochrome P450 1A1 (CYP1A1) in cancer cells. CYP1A1
      metabolizes these compounds into their reactive metabolites, which are proven to
      mediate their anticancer effect through DNA adduct formation. However, the drug
      metabolite-DNA binding has not been explored so far. Hence, understanding the
      binding characteristics and molecular recognition for drug metabolites with DNA
      is of practical and fundamental interest. The present study is aimed to model
      binding preference shown by reactive metabolites of 5F-203 and 5-AMF with DNA in
      forming DNA adducts. To perform this, three different DNA crystal structures
      covering sequence diversity were selected, and 12 DNA-reactive metabolite
      complexes were generated. Molecular dynamics simulations for all complexes were
      performed using AMBER 11 software after development of protocol for DNA-reactive
      metabolite system. Furthermore, the MM-PBSA/GBSA energy calculation, per
      nucleotide energy decomposition, and Molecular Electrostatic Surface Potential
      analysis were performed. The results obtained from present study clearly indicate
      that minor groove in DNA is preferable for binding of reactive metabolites of
      anticancer compounds. The binding preferences shown by reactive metabolites were
      also governed by specific nucleotide sequence and distribution of electrostatic
      charges in major and minor groove of DNA structure. Overall, our study provides
      useful insights into the initial step of mechanism of reactive metabolite binding
      to the DNA and the guidelines for designing of sequence specific DNA interacting
      anticancer agents.

PMID- 24446379
TI  - Naked eye sensing of toxic metal ions in aqueous medium using thiophene-based
      ligands and its application in living cells.
AB  - Thiophene-based diimine (R1) and monoimine (R2) were synthesized in a single
      step, and their cation binding affinity was tested using colorimetric and UV-vis
      spectral studies. R1 selectively shows a colorimetric turn-on response for
      Pb(2+), Hg(2+) ions and colorimetric turn-off with Sn(2+) ions, and R2 shows
      visual response for Cu(2+) and Hg(2+) over other examined metal ions in aqueous
      medium. R1 forms 1:1 complex with Pb(2+), Hg(2+), and Sn(2+) and exhibits
      fluorescence quenching, whereas R2 shows 2:1 complex with Hg(2+), Cu(2+) and
      shows fluorescence enhancement. The structural and electronic properties of the
      sensors and their metal complexes were also investigated using Density Functional
      Theory calculations. R2 was also successfully demonstrated as a fluorescent probe
      for detecting Cu(2+) ions in living cells.

PMID- 24446380
TI  - Thermodynamics of ligand binding to histone deacetylase like amidohydrolase from
      Bordetella/Alcaligenes.
AB  - Thermodynamic studies on ligand-protein binding have become increasingly
      important in the process of drug design. In combination with structural data and
      molecular dynamics simulations, thermodynamic studies provide relevant
      information about the mode of interaction between compounds and their target
      proteins and therefore build a sound basis for further drug optimization. Using
      the example of histone deacetylases (HDACs), particularly the histone deacetylase
      like amidohydrolase (HDAH) from Bordetella/Alcaligenes, a novel sensitive
      competitive fluorescence resonance energy transfer-based binding assay was
      developed and the thermodynamics of interaction of both fluorescent ligands and
      inhibitors to histone deacetylase like amidohydrolase were investigated. The
      assay consumes only small amounts of valuable target proteins and is suitable for
      fast kinetic and mechanistic studies as well as high throughput screening
      applications. Binding affinity increased with increasing length of aliphatic
      spacers (n = 4-7) between the hydroxamate moiety and the dansyl head group of
      ligand probes. Van't Hoff plots revealed an optimum in enthalpy contribution to
      the free energy of binding for the dansyl-ligand with hexyl spacer. The
      selectivity in the series of dansyl-ligands against human class I HDAC1 but not
      class II HDACs 4 and 6 increased with the ratio of DeltaH(0)/DeltaG(0). The data
      clearly emphasize the importance of thermodynamic signatures as useful general
      guidance for the optimization of ligands or rational drug design.

PMID- 24446382
TI  - NecroX-5 suppresses sodium nitroprusside-induced cardiac cell death through
      inhibition of JNK and caspase-3 activation.
AB  - Although sodium nitroprusside (SNP) is an effective hypotensive drug and is often
      used in pediatric intensive care units and to treat acute heart failure, clinical
      application of SNP is limited by its cardiotoxicity. NecroX-5 (NX-5) was recently
      developed and has the capacity to inhibit necrotic cell death. No current
      literature addresses whether NX-5 suppresses SNP-induced cell death or its
      mechanism of action. We have investigated the protective role of NX-5 against SNP
      induced cell death in cardiomyocyte-like H9c2 cells. SNP treatment induced severe
      cell death, possibly through phosphorylation of stress-activated protein kinase/c
      Jun NH2-terminal kinase (JNK) and activation of the apoptotic signaling pathway,
      including downregulation of Bcl-2 and cleavage of caspase-3. However, NX-5
      suppresses SNP-induced cell death through inhibition of JNK activation and
      suppression of both downregulation of Bcl-2 protein expression and caspase-3
      cleavage. These findings will provide insights and facilitate development of
      antidotes to SNP toxicity in cardiac cells.

PMID- 24446383
TI  - Xanthomonins I-III: a new class of lasso peptides with a seven-residue
      macrolactam ring.
AB  - Lasso peptides belong to the class of ribosomally synthesized and post
      translationally modified peptides. Their common distinguishing feature is an N
      terminal macrolactam ring that is threaded by the C-terminal tail. This lasso
      fold is maintained through steric interactions. The isolation and
      characterization of xanthomonins I-III, the first lasso peptides featuring
      macrolactam rings consisting of only seven amino acids, is now presented. The
      crystal structure of xanthomonin I and the NMR structure of xanthomonin II were
      also determined. A total of 25 variants of xanthomonin II were generated to probe
      different aspects of the biosynthesis, stability, and fold maintenance. These
      mutational studies reveal the limits such a small ring imposes on the threading
      and show that every plug amino acid larger than serine is able to maintain a heat
      stable lasso fold in the xanthomonin II scaffold. 

PMID- 24446384
TI  - Subcutaneous closure versus no subcutaneous closure after non-caesarean surgical
      procedures.
AB  - BACKGROUND: Most surgical procedures involve a cut in the skin that allows the
      surgeon to gain access to the surgical site. Most surgical wounds are closed
      fully at the end of the procedure, and this review focuses on these. The human
      body has multiple layers of tissues, and the skin is the outermost of these
      layers. The loose connective tissue just beneath the skin is called subcutaneous
      tissue, and this generally contains fat. There is uncertainty about closure of
      subcutaneous tissue after surgery: some surgeons advocate closure of subcutaneous
      tissue, as they consider this closes dead space and leads to a decrease in wound
      complications; others consider closure of subcutaneous tissue to be an
      unnecessary step that increases operating time and involves the use of additional
      suture material without offering any benefit. OBJECTIVES: To compare the benefits
      (such as decreased wound-related complications) and consequences (such as
      increased operating time) of subcutaneous closure compared with no subcutaneous
      closure in participants undergoing non-caesarean surgical procedures. SEARCH
      METHODS: In August 2013 we searched the following databases: Cochrane Wounds
      Group Specialised Register (searched 29 August, 2013); The Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7);
      Ovid MEDLINE (1946 to August Week 3 2013); Ovid MEDLINE (In-Process & Other Non
      Indexed Citations August 28, 2013); Ovid EMBASE (1974 to 2013 Week 34); and EBSCO
      CINAHL (1982 to 23 August 2013). We did not restrict studies with respect to
      language, date of publication or study setting. SELECTION CRITERIA: We included
      only randomised controlled trials (RCTs) comparing subcutaneous closure with no
      subcutaneous closure irrespective of the nature of the suture material(s) or
      whether continuous or interrupted sutures were used. We included all RCTs in the
      analysis, regardless of language, publication status, publication year, or sample
      size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified
      the trials and extracted data. We calculated the risk ratio (RR) with 95%
      confidence intervals (CI) for comparing binary (dichotomous) outcomes between the
      groups and calculated the mean difference (MD) with 95% CI for continuous
      outcomes. We performed meta-analysis using the fixed-effect model and random
      effects model. We performed intention-to-treat analysis whenever possible. MAIN
      RESULTS: Eight RCTs met the inclusion criteria. Six of the trials provided data
      for this review and all of these were at high risk of bias. Six trials randomised
      a total of 815 participants to subcutaneous closure (410 participants) or no
      subcutaneous closure (405 participants). Overall, 7.7% of participants (63/815 of
      participants) developed superficial surgical site infections and there was no
      clear evidence of a difference between the two intervention groups (RR 0.84; 95%
      CI 0.53 to 1.33; very low quality evidence). Only two trials reported superficial
      wound dehiscence, with 7.9% (17/215) of participants developing the problem. It
      is not clear whether the lack of reporting of this outcome in other trials was
      because it did not occur, or was not measured. There was no clear evidence of a
      between-group difference in the proportion of participants who developed
      superficial wound dehiscence in the trials that reported this outcome (RR 0.56;
      95% CI 0.22 to 1.41; very low quality evidence). Only one trial reported deep
      wound dehiscence, which occurred in 8.3% (5/60) of participants. There was no
      clear evidence of a difference in the proportion of participants who developed
      deep wound dehiscence between the two groups (RR 0.25; 95% CI 0.03 to 2.11; very
      low quality evidence). Three trials reported the length of hospital stay and
      found no significant difference between groups (MD 0.10 days; 95% CI -0.45 to
      0.64; very low quality evidence). We do not know whether this review reveals a
      lack of effect or lack of evidence of effect. The confidence intervals for these
      outcomes were wide, and significant benefits or harms from subcutaneous closure
      cannot be ruled out. In addition, none of the trials assessed the impact of
      subcutaneous closure on quality of life, long-term patient outcomes (the follow
      up period in the trials varied between one week and two months after surgery) or
      financial implications to the healthcare provider. AUTHORS' CONCLUSIONS: There is
      currently evidence of very low quality which is insufficient to support or refute
      subcutaneous closure after non-caesarean operations. The use of subcutaneous
      closure has the potential to affect patient outcomes and utilisation of
      healthcare resources. Further well-designed trials at low risk of bias are
      necessary.

PMID- 24446385
TI  - Modeling of 24-hour glucose and insulin profiles in patients with type 2 diabetes
      mellitus treated with biphasic insulin aspart.
AB  - Insulin therapy for diabetes patients is designed to mimic the endogenous insulin
      response of healthy subjects and thereby generate normal blood glucose levels. In
      order to control the blood glucose in insulin-treated diabetes patients, it is
      important to be able to predict the effect of exogenous insulin on blood glucose.
      A pharmacokinetic/pharmacodynamic model for glucose homoeostasis describing the
      effect of exogenous insulin would facilitate such prediction. Thus the aim of
      this work was to extend the previously developed integrated glucose-insulin (IGI)
      model to predict 24-hour glucose profiles for patients with Type 2 diabetes
      following exogenous insulin administration. Clinical data from two trials were
      included in the analysis. In both trials, 24-hour meal tolerance tests were used
      as the experimental setup, where exogenous insulin (biphasic insulin aspart) was
      administered in relation to meals. The IGI model was successfully extended to
      include the effect of exogenous insulin. Circadian variations in glucose
      homeostasis were assessed on relevant parameters, and a significant improvement
      was achieved by including a circadian rhythm on the endogenous glucose production
      in the model. The extended model is a useful tool for clinical trial simulation
      and for elucidating the effect profile of new insulin products. 

PMID- 24446386
TI  - Interferon beta-related nephropathy and interstitial lung disease: a new
      association and a long-term warning.
AB  - We report on a so-far never described association between glomerulonephritis and
      sarcoid-like lung disease after long-term interferon beta (IFNb) treatment for
      relapsing-remitting multiple sclerosis. The interest in this case resides in the
      documented remission after IFNb discontinuation. The history of IFNb-related
      adverse events is probably not yet completely written. The rapid reversal of the
      pathological signs in our patient underlines the importance of careful clinical
      and laboratory surveillance, including kidney functional parameters, for an early
      diagnosis of IFNb-related diseases.

PMID- 24446388
TI  - Herbicides and plant hormesis.
AB  - Herbicide hormesis is commonly observed at subtoxic doses of herbicides and other
      phytotoxins. The occurrence and magnitude of this phenomenon are influenced by
      plant growth stage and physiological status, environmental factors, the endpoint
      measured and the timing between treatment and endpoint measurement. The mechanism
      in some cases of herbicide hormesis appears to be related to the target site of
      the herbicide, whereas in other examples hormesis may be by overcompensation to
      moderate stress induced by the herbicides or a response to disturbed homeostasis.
      Theoretically, herbicide hormesis could be used in crop production, but this has
      been practical only in the case of the use of herbicides as sugar cane 'ripeners'
      to enhance sucrose accumulation. The many factors that can influence the
      occurrence, the magnitude and the dose range of hormetic increases in yield for
      most crops make it too unpredictable and risky as a production practice with the
      currently available knowledge. Herbicide hormesis can cause undesired effects in
      situations in which weeds are unintentionally exposed to hormetic doses (e.g. in
      adjacent fields, when shielded by crop vegetation). Some weeds that have evolved
      herbicide resistance may have hormetic responses to recommended herbicide
      application rates. Little is known about such effects under field conditions. A
      more complete understanding of herbicide hormesis is needed to exploit its
      potential benefits and to minimize its potential harmful effects in crop
      production.

PMID- 24446387
TI  - Pregnancy, sex and hormonal factors in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is influenced by pregnancy, sex and hormonal
      factors. OBJECTIVES: A comprehensive understanding of the role of pregnancy, sex
      and hormonal factors can provide insights into disease mechanisms, and new
      therapeutic developments and can provide improved patient care and treatment.
      METHODS: Based on an international conference of experts and a comprehensive
      PubMed search for publications on these areas in MS, we provide a review of what
      is known about the impact of these factors on disease demographics, etiology,
      pathophysiology and clinical course and outcomes. RESULTS AND CONCLUSIONS:
      Recommendations are provided for counseling and management of people with MS
      before conception, during pregnancy and after delivery. The use of disease
      modifying and symptomatic therapies in pregnancy is problematic and such
      treatments are normally discontinued. Available knowledge about the impact of
      treatment on the mother, fetus and newborn is discussed. Recommendations for
      future research to fill knowledge gaps and clarify inconsistencies in available
      data are made.

PMID- 24446389
TI  - The relationship between water loss, mechanical stress, and molecular structure
      of human stratum corneum ex vivo.
AB  - Proper hydration of the stratum corneum (SC) is important for maintaining skin's
      vital functions. Water loss causes development of drying stresses, which can be
      perceived as 'tightness', and plays an important role in dry skin damage
      processes. However, molecular structure modifications arising from water loss and
      the subsequent development of stress has not been established. We investigated
      the drying stress mechanism by studying, ex vivo, the behaviors of the SC
      components during water desorption from initially fully hydrated samples using
      Raman spectroscopy. Simultaneously, we measure the SC mechanical stress with a
      substrate curvature instrument. Very good correlations of water loss to the
      mechanical stress of the stratum corneum were obtained, and the latter was found
      to depend mainly on the unbound water fraction. In addition to that, the water
      loss is accompanied with an increase of lipids matrix compactness characterized
      by lower chain freedom, while protein structure showed an increase in amount of
      alpha-helices, a decline in alpha-sheets, and an increase in folding in the
      tertiary structure of keratin. The drying process of SC involves a complex
      interplay of water binding, molecular modifications, and mechanical stress. This
      article provides a better understanding of the molecular mechanism associated to
      SC mechanics.

PMID- 24446390
TI  - A novel estrogen receptor GPER mediates proliferation induced by 17beta-estradiol
      and selective GPER agonist G-1 in estrogen receptor alpha (ERalpha)-negative
      ovarian cancer cells.
AB  - G protein-coupled estrogen receptor (GPER) is recently identified as a membrane
      associated estrogen receptor that mediates non-genomic effects of estrogen. Our
      previous immunohistochemistry study found an association between GPER and the
      proliferation of epithelial ovarian cancer. However, the contributions and
      mechanisms of GPER in the proliferation of ovarian cancers are not clear. We have
      examined the role of GPER in estrogen receptor alpha (ERalpha)-negative/GPER
      positive OVCAR5 ovarian cancer cell line. MTT assay was used to detect cell
      proliferation. BrdU incorporation assay was used to measure the cells in S-phase.
      Protein expression of marker genes of proliferation, cell cycle and apoptosis
      were examined by Western blot. The results showed that 17beta-estradiol and
      selective GPER agonist G-1 stimulated the proliferation of OVCAR5 cells and
      increased the cells in S-phase. Both ligands upregulated the protein levels of c
      fos and cyclin D1. Small interfering RNA targeting GPER or G protein inhibitor
      pertussin toxin (PTX) inhibited basal cell proliferation and attenuated 17beta
      estradiol- or G-1-induced cell proliferation. GPER mediated cell growth was also
      associated with the apoptosis of OVCAR5 cells. These findings suggest that GPER
      has an important function in the proliferation of ovarian cancer cells lacking
      ERalpha. GPER might be a promising therapeutic target in ovarian cancer. 

PMID- 24446392
TI  - Flavoenzyme-catalyzed formation of disulfide bonds in natural products.
AB  - Nature provides a rich source of compounds with diverse chemical structures and
      biological activities, among them, sulfur-containing metabolites from bacteria
      and fungi. Some of these compounds bear a disulfide moiety that is indispensable
      for their bioactivity. Specialized oxidoreductases such as GliT, HlmI, and DepH
      catalyze the formation of this disulfide bridge in the virulence factor
      gliotoxin, the antibiotic holomycin, and the anticancer drug romidepsin,
      respectively. We have examined all three enzymes by X-ray crystallography and
      activity assays. Despite their differently sized substrate binding clefts and
      hence, their diverse substrate preferences, a unifying reaction mechanism is
      proposed based on the obtained crystal structures and further supported by
      mutagenesis experiments. 

PMID- 24446393
TI  - Analysis of new biomarkers for cholangiocarcinoma.
AB  - Cholangiocarcinoma is one of the most serious diseases in northeast Thailand,
      where its incidence is reported to be the highest in the world. We tried to
      develop a new method to detect cholangiocarcinoma in the early stages using serum
      proteins. We found that after fluorescent labeling of the sugar moiety of serum
      proteins, a new peak was identified, which might be a promising marker for
      cholangiocarcinoma. 

PMID- 24446394
TI  - Artesunate exerts an anti-immunosuppressive effect on cervical cancer by
      inhibiting PGE2 production and Foxp3 expression.
AB  - Artesunate (ART), derived from a common traditional Chinese medicine, has beeen
      used an antimalarial for several years. In this study, the effect and mechanism
      of ART on anti-human cervical cancer cells was examined. The level of
      prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells
      (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor
      activity was investigated in mice with cervical cancer by the subcutaneous
      injection of various concentrations of ART. The concentrations of PGE2 in the
      supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2
      (COX-2) and Foxp3 expression were determined using quantitative polymerase chain
      reaction (qPCR) and western blot analysis. The effect of ART on the viability of
      CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and
      the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were
      significantly higher in cervical cancer patients and mice with cervical cancer.
      ART was capable of inhibiting orthotopic tumor growth, which correlated with a
      decrease in the level of PGE2 and the percentage of Treg cells in mice with
      cervical cancer. Furthermore, ART decreased COX-2 expression and the production
      of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated
      with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of
      being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti
      tumor effect against cervical cancer by inhibition of PGE2 production in CaSki
      and Hela cells, which resulted in the decrease of Foxp3 expression in T cells.
      Therefore, ART may be an effective drug for immunotherapy of cervical cancer. 

PMID- 24446395
TI  - Current state of herbicides in herbicide-resistant crops.
AB  - Current herbicide and herbicide trait practices are changing in response to the
      rapid spread of glyphosate-resistant weeds. Growers urgently needed glyphosate
      when glyphosate-resistant crops became available because weeds were becoming
      widely resistant to most commonly used selective herbicides, making weed
      management too complex and time consuming for large farm operations. Glyphosate
      made weed management easy and efficient by controlling all emerged weeds at a
      wide range of application timings. However, the intensive use of glyphosate over
      wide areas and concomitant decline in the use of other herbicides led eventually
      to the widespread evolution of weeds resistant to glyphosate. Today, weeds that
      are resistant to glyphosate and other herbicide types are threatening current
      crop production practices. Unfortunately, all commercial herbicide modes of
      action are over 20 years old and have resistant weed problems. The severity of
      the problem has prompted the renewal of efforts to discover new weed management
      technologies. One technology will be a new generation of crops with resistance to
      glyphosate, glufosinate and other existing herbicide modes of action. Other
      technologies will include new chemical, biological, cultural and mechanical
      methods for weed management. From the onset of commercialization, growers must
      now preserve the utility of new technologies by integrating their use with other
      weed management technologies in diverse and sustainable systems.

PMID- 24446396
TI  - Interobserver variability of radiographic pulmonary nodule diameter measurements
      in dogs and cats.
AB  - The purpose of this study was to determine the interobserver variability of
      radiographic pulmonary nodule diameter measurements among readers with varying
      levels of experience. Because interobserver variability may lead to inaccurate
      estimations of nodule growth on repeat radiographic assessment, an incorrect
      presumption of malignant etiology or misclassification of tumor response to
      treatment may result. The maximum diameters of 47 pulmonary nodules from 22 dogs
      and 7 cats were measured. Measurements were performed using one digital thoracic
      radiographic projection by eight clinicians. The eight clinicians included two
      interns, two residents, two board-certified veterinary specialists, and two board
      certified veterinary radiologists. A mixed-effect analysis of variance model was
      used to evaluate the contribution of reader, experience level, patient, nodule,
      and nodule size to the overall variability in mean pulmonary nodule diameter. The
      interobserver variability in diameter measurement for any given nodule was 16%,
      and experience level and nodule size classification did not contribute to
      measurement variability. Linear measurements of the diameter of a pulmonary
      nodule can vary significantly among a group of clinicians; however, depending on
      the criteria used to evaluate nodule growth or tumor response, the 16%
      interobserver variability reported here is likely not clinically significant. 

PMID- 24446397
TI  - Canine keratomycosis in 11 dogs: a case series (2000-2011).
AB  - Keratomycosis is rarely reported in dogs. The purpose of this study was to review
      the signalment, clinical characteristics, predisposing factors, and outcome of 11
      cases of canine keratomycosis. Medical records of included dogs were reviewed and
      follow-up information was obtained by re-examination of patients following their
      initial diagnosis. All 11 patients possessed predisposing factors for fungal
      keratitis, including an underlying endocrinopathy, pre-existing corneal disease,
      intraocular surgery, and/or prolonged use of either topical antibiotics or
      corticosteroids at the time of initial examination. Diagnostic techniques
      included corneal cytology demonstrating yeast or hyphae in 6 of 11 eyes, and
      fungal cultures with positive results in 7 of 11 eyes. Fungal organisms isolated
      included Cladosporium spp. (n = 1), Chrysosporium spp. (n = 1), Curvularia spp.
      (n = 2), Aspergillus spp. (n = 1), Penicillium spp. (n = 1), and Phialemonium
      spp. (n = 1). Of the 11 patients, 6 responded to medical management alone. Two
      resolved after a superficial keratectomy, and three were enucleated due to either
      endophthalmitis or progression of corneal disease. This study identified
      potential risk factors for developing fungal keratitis. 

PMID- 24446398
TI  - Upper thoracic disc disease (T1-T9) in large-breed dogs.
AB  - The purpose of this study was to identify large-breed dogs with intervertebral
      disc disease (IVDD) in the upper thoracic region (thoracic vertebrae 1-9 [T1
      T9]). Medical records of all dogs that were diagnosed with IVDD on MRI between
      February 2008 and September 2011 were reviewed. Of 723 dogs diagnosed with IVDD
      based on MRI, 527 (72.9%) were small-breed dogs. There were 21 (10.7%) large
      breed dogs with IVDD in the T1-T9 region, whereas no small-breed dogs were
      identified with lesions in that region. The most common upper thoracic lesion
      sites were T2-T3 (33.3%) and T4-T5 (25.9%). The majority of dogs with T1-T9
      lesions were German shepherd dogs (52.4%). Larger, older dogs were more likely to
      have T1-T9 lesions and more likely to have multiple regions with IVDD, in
      particular German shepherd dogs (35.1%). Dogs with T1-T9 IVDD were more likely to
      have IVDD in another region (66.7%). All large-breed dogs presenting with T3-L3
      myelopathy should have diagnostic imaging performed of their entire thoracic and
      lumbar spine. 

PMID- 24446399
TI  - Treatment of ibuprofen toxicosis in a dog with IV lipid emulsion.
AB  - A 3 yr old spayed female mixed-breed dog weighing 19.4 kg was evaluated for
      ingestion of 1,856 mg/kg (180 tablets) of ibuprofen, a human formulated
      nonsteroidal anti-inflammatory drug (NSAID). At the time of presentation, the
      patient was alert and hypersalivating, but her mental status rapidly declined to
      obtunded, stuporous, and then comatose within 30 min of presentation. Initial
      treatment included supportive therapy with prostaglandin analogs and antiemetics.
      An IV lipid emulsion (ILE) was administered as a bolus, followed by a constant
      rate infusion. Clinical signs began to improve approximately 3 hr after
      completion of the lipid infusion. The patient required supportive care for 3 days
      before discharge. This case report demonstrates the use of ILE for treatment of
      ibuprofen toxicosis in a dog. ILE infusion may be a therapeutic option for
      patients with toxicosis due to lipid-soluble drugs. 

PMID- 24446400
TI  - The prognostic value of lymph node metastasis with grade 2 MCTs in dogs: 55 cases
      (2001-2010).
AB  - This study evaluates a series of dogs diagnosed with grade 2 cutaneous mast cell
      tumors (MCTs) with concurrent lymph node (LN) metastasis. All dogs had surgical
      excision of the primary tumor. The presence of metastasis was confirmed with
      either histopathology (n = 35) or cytology (n = 20). There was no significant
      difference in survival times (STs) between dogs with and without LN metastasis.
      Median survival time (MST) was not reached at 65.9 mo. LN palpation was a poor
      predictor of metastasis (sensitivity, .71; specificity, .54). Tumor location was
      the only prognostic factor for survival in this series of dogs. ST was greater
      for dogs that had removal of their metastatic LN. This study suggests that in
      dogs with grade 2 MCTs, outcome may not be affected by the presence of LN
      metastasis; however, removal of the metastatic LN may prolong survival. 

PMID- 24446401
TI  - Emphysematous cystitis and pyelonephritis in a nondiabetic dog and a diabetic
      cat.
AB  - Emphysematous cystitis (EC) and emphysematous pyelonephritis (EPN) are the result
      of infection of the urinary bladder and kidneys by gas-producing microorganisms.
      Those infections are most often reported in diabetic patients and rarely occur
      concurrently. This article describes two cases of concurrent EC and EPN, one in a
      nondiabetic dog and the other in a diabetic cat. The use of diagnostic imaging is
      necessary in the diagnosis of emphysematous infections. Both radiography and
      ultrasonography were used in the diagnosis of EC and EPN in the patients
      described in this report. 

PMID- 24446402
TI  - Use of an image-guided robotic radiosurgery system for the treatment of canine
      nonlymphomatous nasal tumors.
AB  - An image-guided robotic stereotactic radiosurgery (SRS) system can be used to
      deliver curative-intent radiation in either single fraction or hypofractionated
      doses. Medical records for 19 dogs with nonlymphomatous nasal tumors treated with
      hypofractionated image-guided robotic stereotactic body radiotherapy (SBRT),
      either with or without adjunctive treatment, were retrospectively analyzed for
      survival and prognostic factors. Median survival time (MST) was evaluated using
      Kaplan-Meier survival curves. Age, breed, tumor type, stage, tumor size,
      prescribed radiation dose, and heterogeneity index were analyzed for prognostic
      significance. Dogs were treated with three consecutive-day, 8-12 gray (Gy)
      fractions of image-guided robotic SBRT. Overall MST was 399 days. No significant
      prognostic factors were identified. Acute side effects were rare and mild. Late
      side effects included one dog with an oronasal fistula and six dogs with
      seizures. In three of six dogs, seizures were a presenting complaint prior to
      SBRT. The cause of seizures in the remaining three dogs could not be definitively
      determined due to lack of follow-up computed tomography (CT) imaging. The
      seizures could have been related to either progression of disease or late
      radiation effect. Results indicate that image-guided robotic SBRT, either with or
      without adjunctive therapy, for canine nonlymphomatous nasal tumors provides
      comparable survival times (STs) to daily fractionated megavoltage radiation with
      fewer required fractions and fewer acute side effects. 

PMID- 24446403
TI  - Pollakiuria and stranguria in a Labrador retriever with penile HSA.
AB  - An approximately 8 yr old castrated male Labrador retriever presented for
      evaluation of weight loss, stranguria, and pollakiuria. Lysis of the proximal one
      third of the os penis was diagnosed on abdominal radiographs, and a positive
      contrast urethrography revealed a smoothly marginated filling defect along the
      dorsal aspect of the urethra at the level of the radiographically observed
      osteolysis. Regional ultrasound revealed an echogenic mass at the proximal aspect
      of the os penis with a severely irregular and discontinuous periosteal surface. A
      penile hemangiosarcoma (HSA) was confirmed on histopathologic evaluation after a
      penile amputation and scrotal urethrostomy were performed. Although HSA is a
      common malignant neoplasm in dogs, lysis of the os penis has not previously been
      documented. Adjunctive chemotherapy, although recommended, was declined, and the
      patient survived 236 days postoperatively. That survival time is considerably
      longer than the average survival time for patients with HSA, other than cutaneous
      forms of HSA. Although an uncommon presentation, HSA of the penis should be
      considered a differential diagnosis in older canines with signs of lower urinary
      tract disease, especially in breeds that have been documented to be predisposed
      to HSA. 

PMID- 24446404
TI  - Emergent presentation of a cat with dystrophin-deficient muscular dystrophy.
AB  - This report describes a case of feline dystrophin-deficient muscular dystrophy
      (DDMD) with an atypical clinical presentation. A novel gene mutation is reported
      to be responsible for dystrophin-deficient hypertrophic muscular dystrophy. In an
      emergency setting, clinicians should be aware of muscular dystrophy in young cats
      and the importance of elevated creatine kinase (CK) activity. Muscular dystrophy
      is rare but can present both a diagnostic and therapeutic challenge in an
      emergency setting. Patients with muscular dystrophy have a progressive disease
      with no specific treatment and have an increased risk for death during their
      hospital stay. 

PMID- 24446405
TI  - Evaluation of extraction sites for evidence of retained tooth roots and
      periapical pathology.
AB  - The objective of this retrospective clinical study was to determine the frequency
      and pathogenicity of unintentional retained tooth root fragments after extraction
      of the maxillary fourth premolar (108 and 208) and mandibular first molar teeth
      (309 and 409) in 74 canine and 42 feline client-owned patients. Radiographs of
      client-owned animals with historical evidence of extraction of teeth 309 and 409
      were reviewed. All patients had dental extraction(s) for clinical reasons, and
      all extractions were deemed successful by the practitioners. Extraction sites
      were radiographed to identify tooth root fragments and pathology. Twenty-five
      canine and 25 feline patients that had extractions utilizing preoperative and
      postoperative radiography were also included. Sixty-one of 74 canine patients
      (82.4%; P < 0.0001) and 39 of 42 feline patients (92.8%; P < 0.0001) had evidence
      of retained tooth root fragments. In total, 100 of 116 cases (86.4%; P < 0.0001)
      had retained tooth root fragments, and periapical pathology was found in 66 of
      116 (56.8%; P = 0.000000743) radiographs, including 39 of 74 canine cases (52.7%;
      P = 0.00002765) and 27 of 42 feline cases (64.3%; P = 0.01589). The control group
      had no evidence of retained root fragments. Further veterinary dental training
      and routine use of pre- and postoperative dental radiology are recommended.

PMID- 24446406
TI  - Chronic liver lobe torsion in a cat.
AB  - A 13 yr old castrated male blue British shorthair with a 3 mo history of vomiting
      was diagnosed with a left lateral liver lobe mass following abdominal
      ultrasonography. At the time of celiotomy, liver lobe torsion (LLT) of the left
      lateral lobe was also present. Histopathologic evaluation of the liver mass and
      associated lobe revealed extensive necrosis secondary to chronic torsion. This is
      the second reported case of LLT in a cat. Both cases were associated with liver
      masses. The cat presented in this case remained clinically normal 8 mo
      postoperatively following lobectomy of the affected lobe. 

PMID- 24446408
TI  - Present guidelines for device implantation: clinical considerations and clinical
      challenges from pacing, implantable cardiac defibrillator, and cardiac
      resynchronization therapy.

PMID- 24446407
TI  - Role of fluid dynamics and inflammation in intracranial aneurysm formation.

PMID- 24446410
TI  - An unusual case of cardiomegaly.

PMID- 24446411
TI  - Executive summary: heart disease and stroke statistics--2014 update: a report
      from the American Heart Association.

PMID- 24446412
TI  - Coronary stent fracture complicated multiple aneurysms confirmed by 3-dimensional
      reconstruction of intravascular-optical coherence tomography in a patient treated
      with open-cell designed drug-eluting stent.

PMID- 24446413
TI  - Self-care guide for the heart failure patient.

PMID- 24446415
TI  - Letter by Stollberger and Finsterer regarding article, "mortality and sudden
      death in pediatric left ventricular noncompaction in a tertiary referral center".

PMID- 24446416
TI  - Response to letter regarding article, "mortality and sudden death in pediatric
      left ventricular noncompaction in a tertiary referral center".

PMID- 24446418
TI  - SpinPhox/iridium(I)-catalyzed asymmetric hydrogenation of cyclic alpha-alkylidene
      carbonyl compounds.
AB  - Optically active medium-sized cyclic carbonyl compounds bearing an alpha-chiral
      carbon center are of interest in pharmaceutical sciences and asymmetric
      synthesis. Herein, SpinPhox/Ir(I) catalysts have been demonstrated to be highly
      enantioselective in the asymmetric hydrogenation of the C?C bonds in the
      exocyclic alpha,beta-unsaturated cyclic carbonyls, including a broad range of
      alpha-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is
      noteworthy that the procedure can be successfully used in the asymmetric
      hydrogenation of the challenging alpha-alkylidenelactam substrates with six- or
      seven-membered rings, thus affording the corresponding optically active carbonyl
      compounds with an alpha-chiral carbon center in generally excellent enantiomeric
      excesses (up to 98 % ee). Synthetic utility of the protocol has also been
      demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen
      and its analogue, as well as biologically important epsilon-aminocaproic acid
      derivatives. 

PMID- 24446419
TI  - Analysis, structural characterization, and bioactivity of oligosaccharides
      derived from lactose.
AB  - The increasing interest for prebiotic carbohydrates as functional food
      ingredients has promoted the synthesis of galactooligosaccharides and new lactose
      derivatives. This review provides a comprehensive overview on the chromatographic
      analysis, structural characterization, and bioactivity studies of lactose-derived
      oligosaccharides. The most common chromatographic techniques used for the
      separation and structural characterization of this type of oligosaccharides,
      including GC and HPLC in different operational modes, coupled to various
      detectors are discussed. Insights on oligosaccharide MS fragmentation patterns,
      using different ionization sources and mass analyzers, as well as data on
      structural analysis by NMR spectroscopy are also described. Finally, this article
      deals with the bioactive effects of galacto oligosaccharides and oligosaccharides
      derived from lactulose on the gastrointestinal and immune systems, which support
      their consumption to provide significant health benefits. 

PMID- 24446417
TI  - A robust method for genome-wide association meta-analysis with the application to
      circulating insulin-like growth factor I concentrations.
AB  - Genome-wide association studies (GWAS) offer an excellent opportunity to identify
      the genetic variants underlying complex human diseases. Successful utilization of
      this approach requires a large sample size to identify single nucleotide
      polymorphisms (SNPs) with subtle effects. Meta-analysis is a cost-efficient means
      to achieve large sample size by combining data from multiple independent GWAS;
      however, results from studies performed on different populations can be variable
      due to various reasons, including varied linkage equilibrium structures as well
      as gene-gene and gene-environment interactions. Nevertheless, one should expect
      effects of the SNP are more similar between similar populations than those
      between populations with quite different genetic and environmental backgrounds.
      Prior information on populations of GWAS is often not considered in current meta
      analysis methods, rendering such analyses less optimal for the detecting
      association. This article describes a test that improves meta-analysis to
      incorporate variable heterogeneity among populations. The proposed method is
      remarkably simple in computation and hence can be performed in a rapid fashion in
      the setting of GWAS. Simulation results demonstrate the validity and higher power
      of the proposed method over conventional methods in the presence of
      heterogeneity. As a demonstration, we applied the test to real GWAS data to
      identify SNPs associated with circulating insulin-like growth factor I
      concentrations. 

PMID- 24446420
TI  - Differentiation potential of menstrual blood- versus bone marrow-stem cells into
      glial-like cells.
AB  - Menstrual blood is easily accessible, renewable, and inexpensive source of stem
      cells that have been interested for cell therapy of neurodegenerative diseases.
      In this study, we showed conversion of menstrual blood stem cells (MenSCs) into
      clonogenic neurosphere- like cells (NSCs), which can be differentiated into glial
      like cells. Moreover, differentiation potential of MenSCs into glial lineage was
      compared with bone marrow stem cells (BMSCs). Differentiation potential of
      individual converted NSCs derived from MenSCs or BMSCs into glial-like cells was
      investigated using immunofluorescence staining and real-time polymerase chain
      reaction.The fibroblastic morphology of both MenSCs and BMSCs was turned into
      NSCs shape during first step of differentiation. NSCs derived from both BMSCs and
      MenSCs expressed higher levels of Olig-2 and Nestin markers compared to
      undifferentiated cells. The expression levels of myelin basic protein (MBP) mRNA
      up regulated only in BMSCs-NSCs no in MenSCs-NSCs. However, outgrowth of
      individual NSCs derived from both MenSCs and BMSCs into glial-like cells led to
      significant up regulation of glial fibrillary acidic protein,Olig-2 and MBP at
      mRNA and protein level accompanied with down regulation of Nestin protein.This is
      the first study demonstrating that MenSCs can be converted to NSCs with
      differentiation ability into glial-like cells. Accumulative data show different
      expression pattern of glial markers in differentiated MenSCs compared to BMSCs.
      The comparable differentiation potential, more accessibility and no invasive
      technique for sample collection of MenSCs in comparison with BMSCs introduce
      MenSCs as an apt, consistent and safe alternative to BMSCs for cell therapy of
      neurodegenerative diseases. 

PMID- 24446421
TI  - Hilar cholangiocarcinoma is pathologically similar to pancreatic duct
      adenocarcinoma: suggestions of similar background and development.
AB  - Routine experiences suggest that cholangiocarcinomas (CCAs) show different
      clinicopathological behaviors along the biliary tree, and hilar CCA apparently
      resembles pancreatic duct adenocarcinoma (PDAC). Herein, the backgrounds for
      these similarities were reviewed. While all cases of PDAC, hilar CCA,
      intrahepatic CCA (ICCA) and CCA components of combined hepatocellular
      cholangiocarcinoma (cHC-CCA) were adenocarcinomas, micropapillary patterns and
      columnar carcinoma cells were common in PDAC and hilar CCA, and trabecular
      components and cuboidal carcinoma cells were common in ICCA and CCA components of
      cHC-CCA. Anterior gradient protein-2 and S100P were frequently expressed in
      perihilar CCA and PDAC, while neural cell adhesion molecule and luminal
      epithelial membrane antigen were common in CCA components of c-HC-CCA. Pdx1 and
      Hes1 were frequently and markedly expressed aberrantly in PDAC and perihilar CCA,
      although their expression was rare and mild in CCA components in cHC-CCA and
      ICCA. Hilar CCA showed a similar postoperative prognosis to PDAC but differed
      from ICCA and cHC-CCA. Taken together, hilar CCA may differ from ICCA and CCA
      components of cHC-CCA but have a similar development to PDAC. These similarities
      may be explained by the unique anatomical, embryological and reactive nature of
      the pancreatobiliary tract. Further studies of these intractable malignancies are
      warranted. 

PMID- 24446422
TI  - Evolution of resistance to phytoene desaturase and protoporphyrinogen oxidase
      inhibitors--state of knowledge.
AB  - Two major classes of herbicides include inhibitors of protoporphyrinogen oxidase
      (PPO) and phytoene desaturase (PDS). Plants can evolve resistance to PPO and PDS
      inhibitors via several mechanisms that include physical changes, resulting in
      reduced uptake, physiological changes, resulting in compartmentalization or
      altered translocation, and biochemical changes, resulting in enhanced metabolic
      degradation or alterations of protein structures, leading to loss of sensitivity
      to the herbicides. This review discusses the involvement of some of these
      mechanisms in the various cases of resistance to PDS- and PPO-inhibiting
      herbicides, and highlights unique aspects of target-site resistance to these
      herbicides.

PMID- 24446423
TI  - Staphylococcus aureus ST398 detected in pigs in Australia.

PMID- 24446425
TI  - 17O and 33S nuclear magnetic shielding of sulfur trioxides from the experimental
      measurements and theoretical calculations.
AB  - In a recent (17)O NMR spectra of liquid sulfur trioxide, several unexpected peaks
      appeared with the temperature-dependent integrated peak ratio. In order to
      interpret NMR spectra and assign peaks to possible molecular structures, the
      theoretical quantum mechanical density functional theory and Moller-Plesset
      second-order perturbation theory calculations were performed. It is suggested
      that in the liquid sulfur trioxide, apart from monomeric SO3, a significant
      amount of (SO3)3 cyclic trimers should appear. No theoretical data support
      hypothesis on (SO3)2 dimers formation.

PMID- 24446426
TI  - Sentinel lymph node status in Merkel cell carcinoma of the head and neck: not a
      predictor of survival.
AB  - BACKGROUND: The effect of sentinel lymph node status on survival in patients with
      Merkel cell carcinoma (MCC) of the head and neck is uncertain. METHODS: We used
      the Surveillance Epidemiology and End Results (SEER) database to identify
      patients with MCC who underwent sentinel lymph node biopsy (SLNB).
      Clinicopathologic data and disease-specific survival (DSS) were compared among
      patients with positive and negative sentinel lymph nodes. RESULTS: We identified
      721 patients with cutaneous MCC who underwent SLNB, of which 173 (24%) had head
      and neck MCC. The rate of sentinel lymph node positivity in patients with head
      and neck MCC was 23.1%. Sentinel lymph node metastasis did not significantly
      affect survival in head and neck MCC (p = .139). CONCLUSION: Using the SEER
      database, we report what we believe to be the largest head and neck MCC study to
      date. Our results suggest that sentinel lymph node status does not predict
      survival in head and neck MCC. Independent predictors of MCC-related mortality
      seem to be unique in the head and neck region.

PMID- 24446424
TI  - Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian
      subjects on nevirapine-containing antiretroviral therapy.
AB  - OBJECTIVES: Artesunate plus amodiaquine is used for malaria treatment in regions
      with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with
      antiretroviral therapy (ART) may result in drug-drug interactions, but minimal
      data exist. This study evaluated the impact of nevirapine-based ART, containing a
      backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its
      active metabolite, desethylamodiaquine (DEAQ). METHODS: This was an open-label,
      parallel-group pharmacokinetic comparison between HIV-infected, adult subjects
      receiving steady-state nevirapine-based ART (n = 10) and ART-naive subjects
      (control group, n = 11). All subjects received a loose formulation of
      artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic
      sampling over 96 h following the final dose of artesunate/amodiaquine.
      Amodiaquine and DEAQ were quantified using a validated HPLC method with UV
      detection. Pharmacokinetic parameters were determined using standard non
      compartmental methods. RESULTS: Exposures to both amodiaquine and DEAQ were
      significantly lower in the nevirapine-based ART group compared with the control
      group (amodiaquine AUC0-24 145 versus 204 ng.h/mL, P = 0.02; DEAQ AUC0-96 14,571
      versus 21,648 ng.h/mL, P < 0.01). The AUCDEAQ/AUC(amodiaquine) ratio was not
      different between groups (ART group 116 versus control group 102, P = 0.67).
      CONCLUSIONS: Subjects on nevirapine-based ART had lower exposure to both
      amodiaquine and DEAQ (28.9% and 32.7%, respectively). Consequently, this may
      negatively impact the effectiveness of artesunate/amodiaquine in HIV-infected
      individuals on this ART combination.

PMID- 24446427
TI  - Ambient lithium-SO2 batteries with ionic liquids as electrolytes.
AB  - Li-SO2 batteries have a high energy density but bear serious safety problems that
      are associated with pressurized SO2 and flammable solvents in the system. Herein,
      a novel ambient Li-SO2 battery was developed through the introduction of ionic
      liquid (IL) electrolytes with tailored basicities to solvate SO2 by reversible
      chemical absorption. By tuning the interactions of ILs with SO2, a high energy
      density and good discharge performance with operating voltages above 2.8 V were
      obtained. This strategy based on reversible chemical absorption of SO2 in IL
      electrolytes enables the development of the next generation of ambient Li-SO2
      batteries.

PMID- 24446428
TI  - Histological features of precancerous and early cancerous lesions of biliary
      tract carcinoma.
AB  - Biliary tract carcinoma develops within the intrahepatic or extrahepatic biliary
      tree and gallbladder. Primary sclerosing cholangitis, hepatolithiasis, congenital
      choledochal cyst, liver fluke infection, pancreatobiliary maljunction, toxic
      exposures and hepatitis virus infection are risk factors for the development of
      human biliary carcinoma. The precise molecular abnormalities of biliary
      carcinogenesis are still unknown, but chronic inflammatory conditions induce the
      production of reactive oxygen or nitrogen species leading to DNA damage. Recent
      studies indicate that cholangiocarcinoma of the large bile duct may arise in
      premalignant lesions such as biliary intraepithelial neoplasm (BilIN) and
      intraductal papillary neoplasm of the bile duct (IPNB). BilIN and IPNB are
      generally confined to the large and septal-sized bile duct. BilINs are
      occasionally observed in non-biliary liver cirrhosis as well as chronic biliary
      disease. In contrast, the precursor lesion of intrahepatic cholangiocarcinoma of
      the small bile duct type remains unclear. We herein demonstrated the histological
      characteristics of different tumor development pathways from premalignant lesion
      to carcinoma in different sites of the biliary tree. 

PMID- 24446429
TI  - Predicting plant invasions under climate change: are species distribution models
      validated by field trials?
AB  - Climate change may facilitate alien species invasion into new areas, particularly
      for species from warm native ranges introduced into areas currently marginal for
      temperature. Although conclusions from modelling approaches and experimental
      studies are generally similar, combining the two approaches has rarely occurred.
      The aim of this study was to validate species distribution models by conducting
      field trials in sites of differing suitability as predicted by the models, thus
      increasing confidence in their ability to assess invasion risk. Three recently
      naturalized alien plants in New Zealand were used as study species
      (Archontophoenix cunninghamiana, Psidium guajava and Schefflera actinophylla):
      they originate from warm native ranges, are woody bird-dispersed species and of
      concern as potential weeds. Seedlings were grown in six sites across the country,
      differing both in climate and suitability (as predicted by the species
      distribution models). Seedling growth and survival were recorded over two summers
      and one or two winter seasons, and temperature and precipitation were monitored
      hourly at each site. Additionally, alien seedling performances were compared to
      those of closely related native species (Rhopalostylis sapida, Lophomyrtus
      bullata and Schefflera digitata). Furthermore, half of the seedlings were sprayed
      with pesticide, to investigate whether enemy release may influence performance.
      The results showed large differences in growth and survival of the alien species
      among the six sites. In the more suitable sites, performance was frequently
      higher compared to the native species. Leaf damage from invertebrate herbivory
      was low for both alien and native seedlings, with little evidence that the alien
      species should have an advantage over the native species because of enemy
      release. Correlations between performance in the field and predicted suitability
      of species distribution models were generally high. The projected increase in
      minimum temperature and reduced frosts with climate change may provide more
      suitable habitats and enable the spread of these species. 

PMID- 24446430
TI  - Costs and effectiveness of on-farm measures to reduce aquatic risks from
      pesticides in the Netherlands.
AB  - BACKGROUND: The European Union requires growers to implement the principles of
      integrated pest management (IPM) by 2014. This paper provides a quantitative
      overview of the costs and effectiveness of voluntary IPM measures in 15 crops in
      the Netherlands. The authors will focus on aquatic risks and define effectiveness
      as the potential to reduce the risks posed to aquatic organisms. They further
      identify which of these measures have actually been adopted by growers and why
      certain measures have not been adopted. RESULTS: Of the 105 measures evaluated,
      the most effective measures with respect to risk reduction were emission
      reduction and replacement of high-risk pesticides (each up to 80% reduction). IPM
      measures directed towards lowering pesticide use generally showed a smaller risk
      reducing potential. However, 40% of these measures reduced the overall cost of
      pest management. About 60% of all 105 measures were voluntarily implemented by
      growers. The most commonly adopted measures were pest prevention, low-dose
      spraying and spray drift reduction. Cost appeared to be an important incentive
      for adoption; however, other factors such as risk perception, education and
      practicability were equally important. CONCLUSIONS: Voluntary IPM measures have
      significantly contributed to reducing aquatic risks (15-50% risk reduction,
      depending on crop type). Further risk reduction could be achieved if more growers
      were to adopt the most effective measures, such as spray drift reduction and
      replacement of high-risk pesticides. However, IPM has hardly reduced the number
      of pesticide applications, and therefore the dependence on chemical crop
      protection continues to be high.

PMID- 24446431
TI  - Pseudilins: halogenated, allosteric inhibitors of the non-mevalonate pathway
      enzyme IspD.
AB  - The enzymes of the non-mevalonate pathway for isoprenoid biosynthesis have been
      identified as attractive targets with novel modes of action for the development
      of herbicides for crop protection and agents against infectious diseases. This
      pathway is present in many pathogenic organisms and plants, but absent in
      mammals. By using high-throughput screening, we identified highly halogenated
      marine natural products, the pseudilins, to be inhibitors of the third enzyme,
      IspD, in the pathway. Their activity against the IspD enzymes from Arabidopsis
      thaliana and Plasmodium vivax was determined in photometric and NMR-based assays.
      Cocrystal structures revealed that pseudilins bind to an allosteric pocket by
      using both divalent metal ion coordination and halogen bonding. The allosteric
      mode of action for preventing cosubstrate (CTP) binding at the active site was
      elucidated. Pseudilins show herbicidal activity in plant assays and
      antiplasmodial activity in cell-based assays. 

PMID- 24446432
TI  - Clinical relevance of frozen diagnosis of ductal margins in surgery of bile duct
      cancer.
AB  - It is anticipated that free surgical margin is crucial for curative resection of
      bile duct cancer. However, the clinical relevance of the ductal margin is
      somewhat controversial. A role of frozen section diagnosis used for evaluation of
      the ductal margin during surgery is also ambiguous. We reviewed the current
      knowledge about frozen section diagnosis and the clinical relevance of the margin
      status in surgery of the bile duct cancer. Frozen section diagnosis of the ductal
      margin of bile duct cancer is necessary to ensure free margins; however, it is
      quite challenging even for experienced pathologists because the bile duct
      involved with bile duct cancer is often inflamed severely due to obstruction
      and/or insertion of a draining tube, which induces epithelial regeneration with
      atypia. Also accessory ducts/peribiliary glands and their conduits in ductal wall
      can mimic invasive ductal components, which requires careful examination to
      evaluate regenerative change, carcinoma in situ, or invasive carcinoma. Published
      studies assessing an association between the ductal margin state and prognosis in
      relatively large cohorts of patients undergoing surgery for bile duct cancer
      indicate that the ductal margin status is an independent prognostic factor; and
      the ductal margin with carcinoma in situ is comparable to free margin; however,
      the margin with invasive carcinoma is significantly adverse for patients'
      prognoses. 

PMID- 24446433
TI  - Biomimetic RNA-silencing nanocomplexes: overcoming multidrug resistance in cancer
      cells.
AB  - RNA interference (RNAi) is an RNA-dependent gene silencing approach controlled by
      an RNA-induced silencing complex (RISC). Herein, we present a synthetic RISC
      mimic nanocomplex, which can actively cleave its target RNA in a sequence
      specific manner. With high enzymatic stability and efficient self-delivery to
      target cells, the designed nanocomplex can selectively and potently induce gene
      silencing without cytokine activation. These nanocomplexes, which target
      multidrug resistance, are not only able to bypass the P-glycoprotein (Pgp)
      transporter, due to their nano-size effect, but also effectively suppress Pgp
      expression, thus resulting in successful restoration of drug sensitivity of
      OVCAR8/ADR cells to Pgp-transportable cytotoxic agents. This nanocomplex approach
      has the potential for both functional genomics and cancer therapy. 

PMID- 24446435
TI  - WITHDRAWN: Fibulin 2, a tyrosine o-sulfated protein, is up-regulated following
      retinal detachment.
AB  - The manuscript has been withdrawn by the author.

PMID- 24446434
TI  - Sirt2 deacetylase is a novel AKT binding partner critical for AKT activation by
      insulin.
AB  - AKT/PKB kinases transmit insulin and growth factor signals downstream of
      phosphatidylinositol 3-kinase (PI3K). AKT activation involves phosphorylation at
      two residues, Thr(308) and Ser(473), mediated by PDK1 and the mammalian target of
      rapamycin complex 2 (mTORC2), respectively. Impaired AKT activation is a key
      factor in metabolic disorders involving insulin resistance, whereas
      hyperactivation of AKT is linked to cancer pathogenesis. Here, we identify the
      cytoplasmic NAD(+)-dependent deacetylase, Sirt2, as a novel AKT interactor,
      required for optimal AKT activation. Pharmacological inhibition or genetic down
      regulation of Sirt2 diminished AKT activation in insulin and growth factor
      responsive cells, whereas Sirt2 overexpression enhanced the activation of AKT and
      its downstream targets. AKT was prebound with Sirt2 in serum or glucose-deprived
      cells, and the complex dissociated following insulin treatment. The binding was
      mediated by the pleckstrin homology and the kinase domains of AKT and was
      dependent on AMP-activated kinase. This regulation involved a novel AMP-activated
      kinase-dependent Sirt2 phosphorylation at Thr(101). In cells with constitutive
      PI3K activation, we found that AKT also associated with a nuclear sirtuin, Sirt1;
      however, inhibition of PI3K resulted in dissociation from Sirt1 and increased
      association with Sirt2. Sirt1 and Sirt2 inhibitors additively inhibited the
      constitutive AKT activity in these cells. Our results suggest potential
      usefulness of Sirt1 and Sirt2 inhibitors in the treatment of cancer cells with up
      regulated PI3K activity and of Sirt2 activators in the treatment of insulin
      resistant metabolic disorders. 

PMID- 24446436
TI  - The expression of Fn14 via mechanical stress-activated JNK contributes to
      apoptosis induction in osteoblasts.
AB  - Bone mass is maintained by the balance between the activities of bone-forming
      osteoblasts and bone-resorbing osteoclasts. It is well known that adequate
      mechanical stress is essential for the maintenance of bone mass, whereas excess
      mechanical stress induces bone resorption. However, it has not been clarified how
      osteoblasts respond to different magnitudes of mechanical stress. Here we report
      that large-magnitude (12%) cyclic stretch induced Ca(2+) influx, which activated
      reactive oxygen species generation in MC3T3-E1 osteoblasts. Reactive oxygen
      species then activated the ASK1-JNK/p38 pathways. The activated JNK led to
      transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF
      receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently
      acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of
      apoptosis, and underwent apoptosis. On the other hand, the ASK1-p38 pathway
      induced expression of the monocyte chemoattractant protein 3 (MCP-3) gene, which
      promoted chemotaxis of preosteoclasts. In contrast, the ERK pathway was activated
      by small-magnitude stretching (1%) and induced expression of two osteogenic
      genes, collagen Ia (Col1a) and osteopontin (OPN). Moreover, activated JNK
      suppressed Col1a and OPN induction in large-magnitude mechanical stretch-loaded
      cells. The enhanced expression of Fn14 and MCP-3 by 12% stretch and the enhanced
      expression of Col1a and OPN by 1% stretch were also observed in mouse primary
      osteoblasts. These results suggest that differences in the response of
      osteoblasts to varying magnitudes of mechanical stress play a key role in
      switching the mode of bone metabolism between formation and resorption. 

PMID- 24446437
TI  - Mechanism and function of monoclonal antibodies targeting siglec-15 for
      therapeutic inhibition of osteoclastic bone resorption.
AB  - The use of monoclonal antibodies to target functionally important cell-surface
      proteins on bone-resorbing osteoclasts represents a promising approach for
      treatment of cancer-associated bone loss and other skeletal pathologies.
      Previously, we identified Siglec-15, a little studied sialic acid-binding
      receptor, as a candidate target that is highly up-regulated during osteoclast
      differentiation induced by the cytokine receptor activator of NF-kappaB ligand
      (RANKL). In this report, we confirm that Siglec-15 is localized to the plasma
      membrane where it can be targeted by monoclonal antibodies to inhibit
      differentiation of functional osteoclasts in vitro. Furthermore, we found that
      treatment of mice with these antibodies led to a marked increase in bone mineral
      density, consistent with inhibition of osteoclast activity. Interestingly,
      osteoblast numbers were maintained despite the anti-resorptive activity. At the
      molecular level, Siglec-15 interacts with the adapter protein DAP12 and can
      induce Akt activation when clustered on the osteoclast cell surface, which likely
      represents its normal signaling function. Importantly, we discovered that
      monoclonal antibodies induce rapid internalization, lysosomal targeting, and
      degradation of Siglec-15 by inducing receptor dimerization. This study defines a
      key regulatory node that controls osteoclast differentiation and activity
      downstream of RANKL and supports further development of Siglec-15 antibodies as a
      novel class of bone loss therapeutics. 

PMID- 24446438
TI  - Cotinine in children admitted for asthma and readmission.
AB  - OBJECTIVE: To explore the relationship between tobacco smoke exposure (reported
      versus biomarker) and rates of readmission for children hospitalized for asthma.
      METHODS: We enrolled a prospective cohort of 774 children aged 1 to 16 years
      admitted for asthma or bronchodilator-responsive wheezing. The primary outcome
      was at least 1 asthma- or wheeze-related readmission within 1 year. Caregivers
      reported any tobacco exposure at home, in a secondary residence, or in the car.
      We measured serum and saliva cotinine levels with mass spectrometry. We used
      logistic regression to evaluate associations between tobacco exposure and
      readmissions. RESULTS: A total of 619 children had complete tobacco exposure
      data; 57% were African American and 76% had Medicaid. Seventeen percent of
      children were readmitted within 1 year. Tobacco exposure rates were 35.1%, 56.1%,
      and 79.6% by report, serum, and saliva measures, respectively. Caregiver report
      of any tobacco exposure was not associated with readmission (adjusted odds ratio:
      1.18; 95% confidence interval: 0.79-1.89), but having detectable serum or
      salivary cotinine was associated with increased odds of readmission (adjusted
      odds ratio [95% confidence interval]: 1.59 [1.02-2.48] and 2.35 [1.22-4.55],
      respectively). Among children whose caregivers reported no tobacco exposure,
      39.1% had detectable serum cotinine and 69.9% had detectable salivary cotinine.
      Of the children with reported exposure, 87.6% had detectable serum cotinine and
      97.7% had detectable salivary cotinine. CONCLUSIONS: Detectable serum and
      salivary cotinine levels were common among children admitted for asthma and were
      associated with readmission, whereas caregiver report of tobacco exposure was
      not.

PMID- 24446440
TI  - Treatment of congenital generalized lymphangiectasia with propranolol in a
      preterm infant.
AB  - Generalized lymphangiectasia is a rare congenital disorder characterized by
      dilated lymphatic vessels with a fatal prognosis, especially in cases with
      thoracic involvement. We describe the use of propranolol in the therapy of
      generalized lymphangiectasia in a preterm infant with hydrops fetalis.
      Propranolol was well tolerated and effective within the first months. It remains
      to be shown whether propranolol is a treatment option for infants with
      generalized lymphangiectasia. 

PMID- 24446441
TI  - Changes in the incidence of candidiasis in neonatal intensive care units.
AB  - OBJECTIVE: Neonatal invasive candidiasis is associated with significant morbidity
      and mortality. We describe the association between invasive candidiasis and
      changes in use of antifungal prophylaxis, empirical antifungal therapy, and broad
      spectrum antibacterial antibiotics over time. METHODS: We examined data from
      709,325 infants at 322 NICUs managed by the Pediatrix Medical Group from 1997 to
      2010. We determined the cumulative incidence of invasive candidiasis and use of
      antifungal prophylaxis, broad-spectrum antibacterial antibiotics, and empirical
      antifungal therapy by year. RESULTS: We identified 2063 (0.3%) infants with 2101
      episodes of invasive candidiasis. Over the study period, the annual incidence of
      invasive candidiasis decreased from 3.6 episodes per 1000 patients to 1.4
      episodes per 1000 patients among all infants, from 24.2 to 11.6 episodes per 1000
      patients among infants with a birth weight of 750-999 g, and from 82.7 to 23.8
      episodes per 1000 patients among infants with a birth weight <750 g. Fluconazole
      prophylaxis use increased among all infants with a birth weight <1000 g (or <1500
      g), with the largest effect on birth weights <750 g, increasing from 3.8 per 1000
      patients in 1997 to 110.6 per 1000 patients in 2010. The use of broad-spectrum
      antibacterial antibiotics decreased among all infants from 275.7 per 1000
      patients in 1997 to 48.5 per 1000 patients in 2010. The use of empirical
      antifungal therapy increased over time from 4.0 per 1000 patients in 1997 to 11.5
      per 1000 patients in 2010. CONCLUSIONS: The incidence of invasive candidiasis in
      the NICU decreased over the 14-year study period. Increased use of fluconazole
      prophylaxis and empirical antifungal therapy, along with decreased use of broad
      spectrum antibacterial antibiotics, may have contributed to this observation.

PMID- 24446442
TI  - 2010 perinatal GBS prevention guideline and resource utilization.
AB  - OBJECTIVES: To quantify differences in early-onset sepsis (EOS) evaluations,
      evaluation-associated resource utilization, and EOS cases detected, when
      comparing time periods before and after the implementation of an EOS algorithm
      based on the Centers for Disease Control and Prevention (CDC) 2010 guidelines for
      prevention of perinatal Group B Streptococcus (GBS) disease. METHODS:
      Retrospective cohort study of infants born at >=36 weeks' gestation from 2009 to
      2012 in a single tertiary care center. One 12-month period during which EOS
      evaluations were based on the CDC 2002 guideline was compared with a second 12
      month period during which EOS evaluations were based on the CDC 2010 guideline. A
      cost minimization analysis was performed to determine the EOS evaluation
      associated costs and resources during each time period. RESULTS: During the study
      periods, among well-appearing infants >=36 weeks' gestation, EOS evaluations for
      inadequate GBS prophylaxis decreased from 32/1000 to <1/1000 live births; EOS
      evaluation-associated costs decreased by $6994 per 1000 live births; and EOS
      evaluation-associated work hours decreased by 29 per 1000 live births. We found
      no increase in EOS evaluations for other indications, total NICU admissions,
      frequency of infants evaluated for symptoms before hospital discharge, or
      incidence of EOS during the 2 study periods. CONCLUSIONS: Implementation of an
      EOS algorithm based on CDC 2010 GBS guidelines resulted in a 25% decrease in EOS
      evaluations performed among well-appearing infants >=36 weeks' gestation,
      attributable to decreased evaluation of infants born in the setting of inadequate
      indicated GBS prophylaxis. This resulted in significant changes in EOS evaluation
      associated resource expenditures.

PMID- 24446439
TI  - Mortality and morbidity of VLBW infants with trisomy 13 or trisomy 18.
AB  - OBJECTIVE: Little is known about how very low birth weight (VLBW) affects
      survival and morbidities among infants with trisomy 13 (T13) or trisomy 18 (T18).
      We examined the care plans for VLBW infants with T13 or T18 and compared their
      risks of mortality and neonatal morbidities with VLBW infants with trisomy 21 and
      VLBW infants without birth defects. METHODS: Infants with birth weight 401 to
      1500 g born or cared for at a participating center of the Eunice Kennedy Shriver
      National Institute of Child Health and Human Development Neonatal Research
      Network during the period 1994-2009 were studied. Poisson regression models were
      used to examine risk of death and neonatal morbidities among infants with T13 or
      T18. RESULTS: Of 52,262 VLBW infants, 38 (0.07%) had T13 and 128 (0.24%) had T18.
      Intensity of care in the delivery room varied depending on whether the trisomy
      was diagnosed before or after birth. The plan for subsequent care for the
      majority of the infants was to withdraw care or to provide comfort care. Eleven
      percent of infants with T13 and 9% of infants with T18 survived to hospital
      discharge. Survivors with T13 or T18 had significantly increased risk of patent
      ductus arteriosus and respiratory distress syndrome compared with infants without
      birth defects. No infant with T13 or T18 developed necrotizing enterocolitis.
      CONCLUSIONS: In this cohort of liveborn VLBW infants with T13 or T18, the timing
      of trisomy diagnosis affected the plan for care, survival was poor, and death
      usually occurred early.

PMID- 24446443
TI  - Diagnostic and prognostic value of procalcitonin and C-reactive protein in
      malnourished children.
AB  - BACKGROUND: Early recognition of bacterial infections is crucial for their proper
      management, but is particularly difficult in children with severe acute
      malnutrition (SAM). The objectives of this study were to evaluate the accuracy of
      C-reactive protein (CRP) and procalcitonin (PCT) for diagnosing bacterial
      infections and assessing the prognosis of hospitalized children with SAM, and to
      determine the reliability of CRP and PCT rapid tests suitable for remote
      settings. METHODS: From November 2007 to July 2008, we prospectively recruited
      311 children aged 6 to 59 months hospitalized with SAM plus a medical
      complication in Maradi, Niger. Blood, urine, and stool cultures and chest
      radiography were performed systematically on admission. CRP and PCT were measured
      by rapid tests and by reference quantitative methods using frozen serum sent to a
      reference laboratory. RESULTS: Median CRP and PCT levels were higher in children
      with bacteremia or pneumonia than in those with no proven bacterial infection (P
      < .002). However, both markers performed poorly in identifying invasive bacterial
      infection, with areas under the curve of 0.64 and 0.67 before and after excluding
      children with malaria, respectively. At a threshold of 40 mg/L, CRP was the best
      predictor of death (81% sensitivity, 58% specificity). Rapid test results were
      consistent with those from reference methods. CONCLUSIONS: CRP and PCT are not
      sufficiently accurate for diagnosing invasive bacterial infections in this
      population of hospitalized children with complicated SAM. However, a rapid CRP
      test could be useful in these settings to identify children most at risk for
      dying.

PMID- 24446444
TI  - Improving the timeliness of procedures in a pediatric endoscopy suite.
AB  - BACKGROUND AND OBJECTIVE: Pediatric endoscopic procedures are essential in the
      evaluation and treatment of gastrointestinal diseases in children. Although
      pediatric endoscopists are greatly interested in increasing efficiency and
      through-put in pediatric endoscopy units, there is scarcely any literature on
      this critical process. The goal of this study was to improve the timeliness of
      pediatric endoscopy procedures at Children's Hospital at Montefiore. METHODS: In
      June 2010, a pediatric endoscopy quality improvement initiative was formed at
      Children's Hospital at Montefiore. We identified patient-, equipment-, and
      physician-related causes for case delays. Pareto charts, cause and effect
      diagrams, process flow mapping, and statistical process control charts were used
      for analysis. RESULTS: From June 2010 to December 2012, we were able to
      significantly decrease the first case endoscopy delay from an average of 17 to 10
      minutes (P < .001), second case delay from 39 to 25 minutes (P = .01), third case
      delay from 61 to 45 minutes (P = .05), and fourth case delay from 79 to 51
      minutes (P = .05). Total delay time decreased from 196 to 131 minutes, resulting
      in a reduction of 65 minutes (P = .02). From June 2010 to August 2011
      (preintervention period), an average of 36% of first endoscopy cases started
      within 5 minutes, 51% within 10 minutes, and 61% within 15 minutes of the
      scheduled time. From September 2011 to December 2012 (postintervention period),
      the percentage of cases starting within 5 minutes, 10 minutes, and 15 minutes
      increased to 47% (P = .07), 61% (P = .04), and 79% (P = .01), respectively.
      CONCLUSIONS: Applying quality improvement methods and tools helped improve
      pediatric endoscopy timeliness and significantly decreased total delays.

PMID- 24446445
TI  - Diversity and inclusion: strategies to improve pediatrics and pediatric health
      care delivery.

PMID- 24446446
TI  - Variation in quality of tonsillectomy perioperative care and revisit rates in
      children's hospitals.
AB  - OBJECTIVE: To describe the quality of care for routine tonsillectomy at US
      children's hospitals. METHODS: We conducted a retrospective cohort study of low
      risk children undergoing same-day tonsillectomy between 2004 and 2010 at 36 US
      children's hospitals that submit data to the Pediatric Health Information System
      Database. We assessed quality of care by measuring evidence-based processes
      suggested by national guidelines, perioperative dexamethasone and no antibiotic
      use, and outcomes, 30-day tonsillectomy-related revisits to hospital. RESULTS: Of
      139,715 children who underwent same-day tonsillectomy, 10,868 (7.8%) had a 30-day
      revisit to hospital. There was significant variability in the administration of
      dexamethasone (median 76.2%, range 0.3%-98.8%) and antibiotics (median 16.3%,
      range 2.7%-92.6%) across hospitals. The most common reasons for revisits were
      bleeding (3.0%) and vomiting and dehydration (2.2%). Older age (10-18 vs 1-3
      years) was associated with a greater standardized risk of revisits for bleeding
      and a lower standardized risk of revisits for vomiting and dehydration. After
      standardizing for differences in patients and year of surgery, there was
      significant variability (P < .001) across hospitals in total revisits (median
      7.8%, range 3.0%-12.6%), revisits for bleeding (median 3.0%, range 1.0%-8.8%),
      and revisits for vomiting and dehydration (median 1.9%, range 0.3%-4.4%).
      CONCLUSIONS: Substantial variation exists in the quality of care for routine
      tonsillectomy across US children's hospitals as measured by perioperative
      dexamethasone and antibiotic use and revisits to hospital. These data on evidence
      based processes and relevant patient outcomes should be useful for hospitals'
      tonsillectomy quality improvement efforts.

PMID- 24446447
TI  - Patient health questionnaire for school-based depression screening among Chinese
      adolescents.
AB  - OBJECTIVE: The aim of this study was to determine the reliability and validity of
      a Chinese version of the Patient Health Questionnaire-9 item (PHQ-9) and its 2
      subscales (1 item and 2 items) for the screening of major depressive disorder
      (MDD) among adolescents in Taiwan. METHODS: A total of 2257 adolescents were
      recruited from high schools in Taipei. The participants completed assessments
      including demographic information, the Chinese version of the PHQ-9, and the
      Rosenberg Self-Esteem Scale, and data on the number of physical illnesses and
      mental health service utilizations were recorded. Among them, 430 were retested
      using the PHQ-9 within 2 weeks. Child psychiatrists interviewed a subsample of
      the adolescents (n = 165) using the Kiddie-Schedule for Affective Disorder and
      Schizophrenia Epidemiological Version as the criterion standard. RESULTS: The PHQ
      9 had good internal consistency (alpha = 0.84) and acceptable test-retest
      reliability (0.80). The participants with higher PHQ-9 scores were more likely to
      have MDD. Principal component factor analysis of the PHQ-9 yielded a 1-factor
      structure, which accounted for 45.3% of the variance. A PHQ-9 score >=15 had a
      sensitivity of 0.72 and a specificity of 0.95 for recognizing MDD. The area under
      the receiver operating characteristic curve was 0.90. The screening accuracy of
      the 2 subscales was also satisfactory, with a Patient Health Questionnaire-2 item
      cutoff of >=3 being 94.4% sensitive and 82.5% specific and a Patient Health
      Questionnaire-1 item cutoff of >=2 being 61.1% sensitive and 87.7% specific.
      CONCLUSIONS: The PHQ-9 and its 2 subscales appear to be reliable and valid for
      detecting MDD among ethnic Chinese adolescents in Taiwan.

PMID- 24446448
TI  - Asymptomatic tonsillar herniation in a neonate with cleidocranial dysplasia.
AB  - A male neonate was antenatally diagnosed with cleidocranial dysplasia on the
      basis of prenatal ultrasound findings and molecular testing of the RUNX2 gene.
      The patient presented with urosepsis at 24 days of life and subsequently
      developed apneas after endoscopic examination of the vocal cords. Computed
      tomography and MRI studies of the head revealed crowding of the posterior fossa
      with tonsillar and uncal herniation. Apneas were initially thought to be related
      to brainstem compression; however, the patient responded immediately to caffeine
      and subsequently stabilized with antibiotic therapy. To our knowledge, this is
      the first published MRI study of the brain of a neonate with cleidocranial
      dysplasia to demonstrate the striking posterior fossa findings seen secondary to
      the reduced bony skull structures. However, despite the dramatic herniation,
      brainstem function was not compromised. 

PMID- 24446449
TI  - Long-term cardiovascular outcomes in survivors of Kawasaki disease.
AB  - BACKGROUND AND OBJECTIVE: Kawasaki disease (KD) may result in coronary aneurysm
      formation, but there is incomplete knowledge regarding its long-term effects. Our
      objective was to quantify the longer-term rates of adverse cardiac events in a
      modern North American KD cohort. METHODS: Using the Kaiser Permanente Northern
      California population, we performed a retrospective cohort study in patients with
      a history of KD versus matched patients without KD. Chart review was used to
      confirm the diagnosis of KD and all outcomes of interest, including acute
      coronary syndrome, coronary revascularization, heart failure, ventricular
      arrhythmia, valve disease, aortic aneurysm, and all-cause mortality. All outcomes
      occurring at age >=15 years were included in the primary analysis. Outcome rates
      were compared between the 2 groups by using Cox proportional hazards analysis.
      RESULTS: The study included 546 KD patients and 2218 matched patients without KD.
      Seventy-nine percent of the KD patients received intravenous immunoglobulin and
      5% had persistent coronary aneurysm. The average follow-up time was 14.9 years.
      Only 2 KD patients experienced outcomes after age 15 (0.246 events per 1000
      person-years) compared with 7 events in the non-KD group (0.217 events per 1000
      person-years), a nonsignificant difference (hazard ratio: 0.81; 95% confidence
      interval: 0.16-4.0). Within the KD subgroup, persistent coronary aneurysm
      predicted the occurrence of adverse events (P = .007). CONCLUSIONS: This is the
      largest US study of longer-term cardiac outcomes after KD and reveals a low rate
      of adverse cardiovascular events through age 21. Additional validation studies,
      including studies with longer-term follow-up, should be performed.

PMID- 24446450
TI  - Key elements of highly effective teams.

PMID- 24446454
TI  - Proteomic analysis of the sheep caruncular and intercaruncular endometrium
      reveals changes in functional proteins crucial for the establishment of
      pregnancy.
AB  - The expression and regulation of endometrial proteins are crucial for conceptus
      implantation and development. However, little is known about site-specific
      proteome profiles of the mammalian endometrium during the peri-implantation
      period. We utilised a two-dimensional gel electrophoresis/mass spectrometry-based
      proteomics approach to compare and identify differentially expressed proteins in
      sheep endometrium. Caruncular and intercaruncular endometrium were collected on
      days 12 (C12) and 16 (C16) of the oestrous cycle and at three stages of pregnancy
      corresponding to conceptus pre-attachment (P12), implantation (P16) and post
      implantation (P20). Abundance and localisation changes in differentially
      expressed proteins were determined by western blot and immunohistochemistry. In
      caruncular endometrium, 45 protein spots (5% of total spots) altered between day
      12 of pregnancy (P12) and P16 while 85 protein spots (10% of total spots) were
      differentially expressed between P16 and C16. In intercaruncular endometrium, 31
      protein spots (2% of total spots) were different between P12 and P16 while 44
      protein spots (4% of total spots) showed differential expression between C12 and
      C16. The pattern of protein changes between caruncle and intercaruncle sites was
      markedly different. Among the protein spots with implantation-related changes in
      volume, 11 proteins in the caruncular endometrium and six proteins in the
      intercaruncular endometrium, with different functions such as protein synthesis
      and degradation, antioxidant defence, cell structural integrity, adhesion and
      signal transduction, were identified. Our findings highlight the different but
      important roles of the caruncular and intercaruncular proteins during early
      pregnancy. 

PMID- 24446455
TI  - Canada behind in regulating farmyard antibiotics.

PMID- 24446451
TI  - Benzothiazinones mediate killing of Corynebacterineae by blocking decaprenyl
      phosphate recycling involved in cell wall biosynthesis.
AB  - Benzothiazinones (BTZs) are a new class of sulfur containing heterocyclic
      compounds that target DprE1, an oxidoreductase involved in the epimerization of
      decaprenyl-phosphoribose (DPR) to decaprenyl-phosphoarabinose (DPA) in the
      Corynebacterineae, such as Corynebacterium glutamicum and Mycobacterium
      tuberculosis. As a result, BTZ inhibition leads to inhibition of cell wall
      arabinan biosynthesis. Previous studies have demonstrated the essentiality of
      dprE1. In contrast, Cg-UbiA a ribosyltransferase, which catalyzes the first step
      of DPR biosynthesis prior to DprE1, when genetically disrupted, produced a viable
      mutant, suggesting that although BTZ biochemically targets DprE1, killing also
      occurs through chemical synthetic lethality, presumably through the lack of
      decaprenyl phosphate recycling. To test this hypothesis, a derivative of BTZ,
      BTZ043, was examined in detail against C. glutamicum and C. glutamicum::ubiA. The
      wild type strain was sensitive to BTZ043; however, C. glutamicum::ubiA was found
      to be resistant, despite possessing a functional DprE1. When the gene encoding C.
      glutamicum Z-decaprenyl-diphosphate synthase (NCgl2203) was overexpressed in wild
      type C. glutamicum, resistance to BTZ043 was further increased. This data
      demonstrates that in the presence of BTZ, the bacilli accumulate DPR and fail to
      recycle decaprenyl phosphate, which results in the depletion of decaprenyl
      phosphate and ultimately leads to cell death. 

PMID- 24446457
TI  - Children as young as six sniffing gas in Pikangikum.

PMID- 24446456
TI  - Interpretation of cerebrospinal fluid protein tests in the diagnosis of sporadic
      Creutzfeldt-Jakob disease: an evidence-based approach.

PMID- 24446458
TI  - "And you, my father, there on the sad height".

PMID- 24446459
TI  - High H1N1 prevalence and mortality rates a concern.

PMID- 24446460
TI  - Canada owes refugees adequate health coverage.

PMID- 24446461
TI  - Legal storm brewing over Texas forced life-support case.

PMID- 24446462
TI  - Amyloid imaging in atypical dementia.

PMID- 24446463
TI  - Enjoyment of life and declining physical function at older ages: a longitudinal
      cohort study.
AB  - BACKGROUND: Positive affective well-being (i.e., feelings of happiness and
      enjoyment) has been associated with longer survival and reduced incidence of
      serious illness. Our objective was to discover whether enjoyment of life also
      predicted a reduced risk of functional impairment over an 8-year period in a
      large population sample. METHODS: We carried out a prospective analysis involving
      3199 men and women aged 60 years or older from the English Longitudinal Study of
      Ageing. Enjoyment of life was assessed by questionnaire. Outcomes were impairment
      in 2 or more activities of daily living and changes in gait speed on a walking
      test. Covariates included sociodemographic factors, baseline health, depressive
      symptoms, impairment of mobility and health behaviours. RESULTS: Two or more
      impaired activities of daily living developed among 4.4%, 11.7% and 16.8% of
      participants in the high, medium and low enjoyment-of-life tertiles,
      respectively. After adjustment for covariates, the odds of impaired activities of
      daily living developing were 1.83 (95% confidence interval 1.13-2.96) in the low
      compared with high tertile. Gait speed after 8 years was also related to baseline
      enjoyment of life after adjustment for gait speed and other covariates at
      baseline (p < 0.001). We obtained similar results when we limited analyses to
      participants younger than 70 years at baseline. INTERPRETATION: This is an
      observational study, so causal conclusions cannot be drawn. But our results
      provide evidence that reduced enjoyment of life may be related to the future
      disability and mobility of older people.

PMID- 24446464
TI  - Nunavut calls inquest into record number of suicides.

PMID- 24446465
TI  - Ten health stories that mattered: Jan. 13-17.

PMID- 24446466
TI  - Tuning of rigid ankle-foot orthoses is essential.

PMID- 24446468
TI  - Bidirectional optimization of the melting spinning process.
AB  - A bidirectional optimizing approach for the melting spinning process based on an
      immune-enhanced neural network is proposed. The proposed bidirectional model can
      not only reveal the internal nonlinear relationship between the process
      configuration and the quality indices of the fibers as final product, but also
      provide a tool for engineers to develop new fiber products with expected quality
      specifications. A neural network is taken as the basis for the bidirectional
      model, and an immune component is introduced to enlarge the searching scope of
      the solution field so that the neural network has a larger possibility to find
      the appropriate and reasonable solution, and the error of prediction can
      therefore be eliminated. The proposed intelligent model can also help to
      determine what kind of process configuration should be made in order to produce
      satisfactory fiber products. To make the proposed model practical to the
      manufacturing, a software platform is developed. Simulation results show that the
      proposed model can eliminate the approximation error raised by the neural network
      based optimizing model, which is due to the extension of focusing scope by the
      artificial immune mechanism. Meanwhile, the proposed model with the corresponding
      software can conduct optimization in two directions, namely, the process
      optimization and category development, and the corresponding results outperform
      those with an ordinary neural network-based intelligent model. It is also proved
      that the proposed model has the potential to act as a valuable tool from which
      the engineers and decision makers of the spinning process could benefit. 

PMID- 24446469
TI  - Maintenance of rituximab treatment in a patient with primary Sjogren's syndrome.

PMID- 24446470
TI  - The ill endothelium: how atherosclerosis begins in lupus.

PMID- 24446471
TI  - Increased Notch pathway activation in Behcet's disease.
AB  - OBJECTIVE: Behcet's disease (BD) is a refractory inflammatory disorder with
      unknown causes. Since the Notch pathway is critically involved in the immune
      response, the present study was undertaken to investigate the role of this
      pathway in BD. METHODS: Hes-1, Notch 1-4, Jagged-1, DLL-1 and DLL-4 expression,
      frequency of IFN-gamma and IL-17 expressing Th cells, Notch intracellular domain
      (NICD), phosphorylation of signal transducer and activator of transcription 3
      (STAT3) and the production of IFN-gamma and IL-17 were examined by real-time PCR,
      flow cytometry and ELISA. Notch blockade was performed using the gamma-secretase
      inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester
      (DAPT). Transfection with miR-23b mimics and inhibitor was used to examine the
      effect of miR-23b on Notch pathway activation. RESULTS: Active BD patients showed
      an increased activation of the Notch pathway in association with a higher Th17
      response. Notch blockade preferentially inhibited Th17 responses. The effect of
      Notch blockade on the Th17 response was associated with a lower level of STAT3
      phosphorylation. miR-23b was significantly decreased in CD4(+) T cells from
      active BD patients. CD4(+) T cells transfected with miR-23b showed a reduced
      expression of NICD and a reduced frequency of IL-17- and IFN-gamma-expressing T
      cells. CONCLUSION: The present study suggests that an increased activation of the
      Notch pathway may contribute to the pathogenesis of BD. Decreased expression of
      miR-23b may be involved in activation of the Notch pathway in BD. Manipulation of
      the Notch pathway may offer a novel therapeutic approach for BD.

PMID- 24446472
TI  - Surgical treatment of atrial fibrillation: an updated review.
AB  - The first Cox-maze procedure was performed in 1987, demonstrating the feasibility
      of a non-pharmacological treatment for atrial fibrillation (AF). Since then,
      surgery for AF has changed over time, in parallel with technological advances.
      Replacement of surgical incisions with linear ablation lines made a previously
      cumbersome procedure accessible to most surgeons, without compromising success.
      On the other hand, new ablation technologies paved the way for the development of
      minimally invasive surgery, which may potentially extend the scope of surgery to
      patients who would otherwise be deemed unsuitable. Nonetheless, literature on
      minimally invasive surgery is still scarce and randomized clinical trials
      currently under way are expected to shed light on some controversial issues.
      Moreover, successful AF treatment will probably rely on close collaboration
      between surgery and electrophysiology. Indeed, the hybrid procedure, though still
      in its very beginning, seems to combine the best of catheter and surgical
      ablation. However, further studies are warranted to determine the effectiveness
      of this promising strategy, especially in patients with persistent and
      longstanding persistent AF. Better understanding of AF pathophysiology as well as
      more accurate preoperative localization of AF triggers will bring about the
      possibility of tailoring specific lesion sets and ablation modalities to
      individual patients. This, in turn, will increase recovery and maintenance of
      sinus rhythm, with significant benefits in long-term outcomes. 

PMID- 24446473
TI  - Tracheobronchial obstruction: follow-up study of 100 children treated with airway
      stenting.
AB  - OBJECTIVE: We described a cohort of 100 children with a wide variety of airway
      obstruction who underwent stent positioning in the last 7 years. The study
      examined the outcomes of this treatment in the largest series of paediatric
      patients reported in the literature with special concern over safety and clinical
      effectiveness. METHODS: We performed a retrospective analysis of 100 consecutive
      paediatric patients who underwent stent insertions between January 2005 and May
      2012. Statistical analysis was performed and exact likelihood was used. RESULTS:
      A total of 235 stents were placed for severe airway obstruction. One hundred and
      twelve silicone stents (cylinder, hourglass or Y-shaped), 120 metallic stents
      (covered Nitinol stents, expandable coronary and vascular stents) and 3
      biodegradable polydioxanone (PDS) stents were used. Eighty patients presented
      clinical improvement after stent insertion, 17 were weaned off mechanical
      ventilation and 3 showed no significant clinical improvement [95% confidence
      interval (CI) 0.1-8.0%]. Complications were different according to stent type. In
      our cohort, no fatal stent-related complications have been observed. At follow-up
      (median 41.4 months, range 1.1-145.4) complete resolution was registered for 60
      patients (66%; 95% CI 55-76%), 17 are still under treatment, 9 were lost to
      follow-up, 8 underwent surgery and 6 died of causes not stent related.
      CONCLUSION: Airway stenting represents a conservative treatment before more
      invasive surgical procedures and can be very effective when performed in selected
      children and in specialized centres by physicians experienced in rigid and
      flexible bronchoscopy.

PMID- 24446475
TI  - Vertebral artery variations in thoracic aortic patients.
AB  - OBJECTIVES: Arterial variation is common in the vertebral artery, and simple
      occlusion of the left subclavian artery may result in brain infarction,
      especially when it terminates in the posterior inferior cerebellar artery (PICA).
      We report the results of preoperative vertebral artery evaluation by magnetic
      resonance angiography (MRA) and its impact upon operative strategy. METHODS:
      Among the 214 patients who underwent thoracic aortic surgery from 2009 through
      2012, 159 patients with preoperative MRA were retrospectively analysed. Patients'
      age ranged from 35 to 88 (median 72), 122 were male and 115 had degenerative
      aneurysms. Prevalence rates of vertebral artery variations and occlusive lesions
      were reported, together with operative strategies and outcomes. RESULTS: There
      were 19 hypoplasia (12%), 10 PICA termination (6%) and 12 occlusive lesion (8%)
      on the right vertebral artery and 10 hypoplasia (6%), 5 PICA termination (3%), 7
      direct arch origin (4%) and 3 occlusive lesion (2%) on the left. Two of the seven
      arch-originated arteries terminated in the PICA. In aortic arch replacement,
      these were reconstructed together with the left subclavian artery while
      hypothermia was maintained. During thoracic endovascular aortic repair with Zone
      2 proximal landing, debranching bypass was employed to preserve left subclavian
      perfusion when there was PICA termination, hypoplasia or occlusive lesion. In 1
      patient with hypoplasia between the basilar artery and the left PICA, bypass was
      added immediately after deployment because radial pressure dropped critically. No
      brain infarction occurred with this strategy. CONCLUSIONS: PICA termination and
      right side hypoplasia/occlusive lesion, where left subclavian perfusion is
      important for brain protection, is present in ~ 30%. Left vertebral artery that
      originated from the arch should be managed with care, because PICA termination is
      highly prevalent.

PMID- 24446474
TI  - Safety and feasibility of concomitant surgical ablation of atrial fibrillation in
      patients with severely reduced left ventricular ejection fraction.
AB  - OBJECTIVES: Concomitant surgical ablation of atrial fibrillation (AF) is a safe
      and feasible procedure. However, many surgeons are reluctant to perform it in
      patients with heart failure. We investigated the safety and efficacy of AF
      ablation in patients with a severely reduced left ventricular ejection fraction
      (LVEF <35%). METHODS: Between July 2003 and August 2011, 59 patients with
      severely reduced LVEF underwent concomitant surgical AF ablation, by either left
      atrial (LA) lesion set or bilateral pulmonary vein isolation in patients with
      paroxysmal AF, and biatrial lesion set in patients with persistent AF. Follow-up
      echocardiography (ECG) was conducted after 12 months; rhythm monitoring was
      accomplished by either 24-h Holter echocardiography or event recorder monitoring.
      RESULTS: The patients' mean age was 68 +/- 9 years (male patients, 71%).
      Paroxysmal AF was present in 24 (41%) and persistent AF in 35 (59%) patients. No
      ablation-related adverse events occurred. The one-year survival rate was 95%
      without differences in patients with and without restoration of sinus rhythm
      (SR). The overall rate of SR was 54% after 1 year, showing a superior result in
      patients with preoperative paroxysmal AF compared with those with preoperative
      persistent AF (70 vs 41%, P < 0.001). LVEF improved from 29 +/- 8% preoperatively
      to 39 +/- 7% after 12 months of follow-up. The improvement in LVEF was
      significantly higher in patients with restored SR than in those with AF (16 vs
      5%; P < 0.001). Only patients with restoration of SR showed a statistically
      significant reduction in New York Heart Association functional class at the 12
      month follow-up (P = 0.0013). CONCLUSIONS: Surgical AF ablation was safe and
      feasible in patients with severely reduced LVEF. The restoration of SR led to a
      significantly higher improvement in LVEF and alleviation of clinical heart
      failure symptoms, not observed if AF persisted postoperatively.

PMID- 24446476
TI  - A new surgical procedure for palmar hyperhidrosis: is it possible to perform
      endoscopic sympathectomy under deep sedation without intubation?
AB  - OBJECTIVES: Palmar hyperhidrosis (PH) is a common dysfunctional disorder, with
      endoscopic thoracic sympathectomy (ETS) being the most popular treatment method.
      However, until now, there is little improvement to this technique. In this paper,
      we present a new alternative to the conventional surgical method. METHODS: We
      performed ETS with flexible thoracoscopy under deep sedation without intubation
      in 13 patients. All patients were followed up until today. RESULTS: During
      surgery, the vital signs of the patients remained stable and no intubation was
      necessary. The operative times ranged between 30 and 40 min. The symptom of PH
      disappeared postoperatively, and no complications occured. All patients were
      discharged from the hospital on the second postoperative day. CONCLUSIONS: ETS
      with flexible thoracoscopy under deep sedation without intubation is a safe and
      effective method.

PMID- 24446477
TI  - Treatment strategies in the management of severe complications following slide
      tracheoplasty in children.
AB  - OBJECTIVES: This study focuses on the different surgical and endoscopical
      treatment alternatives when dealing with severe complications after slide
      tracheoplasty (STP). METHODS: Retrospective study of patients with symptomatic
      congenital tracheal stenosis (CTS) admitted to a single institution, between
      January 1997 and January 2013, surgically treated by means of STP. The following
      variables were evaluated: demographics, preoperative tracheal stenosis
      characteristics, associated anomalies and outcome measures. RESULTS: Cohort
      included 14 patients (8 males and 6 females) with a mean age of 8.7 months when
      treated (range, 1-43 m). Eleven patients (78%) showed a long segment CTS (>30% of
      total tracheal length) and 9 (64%) had associated cardiac or great vessel
      anomalies (left pulmonary artery sling). Three patients (21%) showed severe
      postoperative complications that required significant airway reintervention:
      tracheal resection of a restenotic segment, laser division with balloon
      dilatation of a residual stenosis and placement of a biodegradable endotracheal
      stent in an extensive tracheal narrowing. All patients are in good clinical
      condition with a mean follow-up of 6.3 years (range, 2 months to 16 years).
      CONCLUSIONS: STP has become the procedure of choice when dealing with CTS.
      Although it shows clear advantages compared with other surgical techniques,
      severe and difficult to manage complications may occur. Surgeons involved in
      their treatment should be familiar with diverse surgical and endoscopical
      procedures. Biodegradable airway stenting is a new and promising technique when
      long and severe post-surgical tracheal stenosis is present.

PMID- 24446478
TI  - Ministernotomy versus conventional sternotomy for aortic valve replacement:
      matched propensity score analysis of 808 patients.
AB  - OBJECTIVES: The proportion of minimally invasive approaches is rising in cardiac
      surgery, in part driven by increasing patient demand. This study aimed to perform
      a risk-adjusted comparison of mortality, rate of stroke and perioperative
      morbidity of aortic valve replacement (AVR) conducted through either partial mini
      sternotomy or conventional sternotomy. METHODS: Between July 2009 and July 2012,
      data from 984 consecutive patients undergoing isolated AVR were prospectively
      recorded. In 44.3% (n = 436), the less invasive partial mini-sternotomy was used.
      Propensity score matching was performed based on 15 preoperative risk factors to
      correct for selection bias. In-hospital mortality, stroke rate as well as other
      major complications in the minimally invasive group and conventional sternotomy
      group were compared in 404 matched patient pairs (total 808). RESULTS: In
      hospital mortality and rate of postoperative intra-aortic balloon pump use were
      identical for propensity-matched patients, 1.0% (4 in each group). The rate of
      stroke [OR (95% confidence interval (CI)): 0.80 (0.22-2.98)], perioperative
      myocardial infarction [OR (95% CI): 2.00 (0.18-22.06)], low-output syndrome [OR
      (95% CI): 0.90 (0.37-2.22)], new onset of dialysis [OR (95% CI): 1.25 (0.49
      3.17)] and re-exploration for bleeding [OR (95% CI): 0.88 (0.50-1.56)] were
      similar. Likewise, resource utilization (operation time, duration of stay in the
      intensive care unit and in-hospital stay) and valve selection (type and size) was
      not affected by the surgical approach either. CONCLUSIONS: AVR can be safely
      conducted through a partial mini-sternotomy. This approach is not associated with
      an increased rate of complications. However, wide CIs reflect the still
      prevailing statistical uncertainty in estimates, not excluding patient-relevant
      differences between approaches. Large trials, which also address end points, such
      as postoperative pain, duration of postoperative recovery and quality of life,
      are needed to clarify the role of minimally invasive AVR.

PMID- 24446479
TI  - Stereolithographic biomodelling of pulmonary hilum by multislice computed
      tomography imaging.

PMID- 24446480
TI  - Jonathon Howard: motor proteins go walkabout. Interview by Caitlin Sedwick.

PMID- 24446481
TI  - Quality control: Genome maintenance in pluripotent stem cells.
AB  - Pluripotent stem cells (PSCs) must maintain their proper genomic content in order
      to preserve appropriate self-renewal and differentiation capacities. However,
      their prolonged in vitro propagation, as well as the environmental culture
      conditions, present serious challenges to genome maintenance. Recent work has
      been focused on potential means to alleviate the genomic insults experienced by
      PSCs, and to detect them as soon as they arise, in order to prevent the
      detrimental consequences of these genomic aberrations on PSC application in basic
      research and regenerative medicine. 

PMID- 24446482
TI  - TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK
      supramolecular structures.
AB  - Nuclear factor kappaB (NF-kappaB) essential modulator (NEMO), a regulatory
      component of the IkappaB kinase (IKK) complex, controls NF-kappaB activation
      through its interaction with ubiquitin chains. We show here that stimulation with
      interleukin-1 (IL-1) and TNF induces a rapid and transient recruitment of NEMO
      into punctate structures that are anchored at the cell periphery. These
      structures are enriched in activated IKK kinases and ubiquitinated NEMO
      molecules, which suggests that they serve as organizing centers for the
      activation of NF-kappaB. These NEMO-containing structures colocalize with
      activated TNF receptors but not with activated IL-1 receptors. We investigated
      the involvement of nondegradative ubiquitination in the formation of these
      structures, using cells deficient in K63 ubiquitin chains or linear ubiquitin
      chain assembly complex (LUBAC)-mediated linear ubiquitination. Our results
      indicate that, unlike TNF, IL-1 requires K63-linked and linear ubiquitin chains
      to recruit NEMO into higher-order complexes. Thus, different mechanisms are
      involved in the recruitment of NEMO into supramolecular complexes, which appear
      to be essential for NF-kappaB activation. 

PMID- 24446483
TI  - Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing
      barrier function.
AB  - Pharmacological focal adhesion kinase (FAK) inhibition prevents tumor growth and
      metastasis, via actions on both tumor and stromal cells. In this paper, we show
      that vascular endothelial cadherin (VEC) tyrosine (Y) 658 is a target of FAK in
      tumor-associated endothelial cells (ECs). Conditional kinase-dead FAK knockin
      within ECs inhibited recombinant vascular endothelial growth factor (VEGF-A) and
      tumor-induced VEC-Y658 phosphorylation in vivo. Adherence of VEGF-expressing
      tumor cells to ECs triggered FAK-dependent VEC-Y658 phosphorylation. Both FAK
      inhibition and VEC-Y658F mutation within ECs prevented VEGF-initiated
      paracellular permeability and tumor cell transmigration across EC barriers. In
      mice, EC FAK inhibition prevented VEGF-dependent tumor cell extravasation and
      melanoma dermal to lung metastasis without affecting primary tumor growth. As
      pharmacological c-Src or FAK inhibition prevents VEGF-stimulated c-Src and FAK
      translocation to EC adherens junctions, but FAK inhibition does not alter c-Src
      activation, our experiments identify EC FAK as a key intermediate between c-Src
      and the regulation of EC barrier function controlling tumor metastasis. 

PMID- 24446484
TI  - A genome-wide screen identifies conserved protein hubs required for cadherin
      mediated cell-cell adhesion.
AB  - Cadherins and associated catenins provide an important structural interface
      between neighboring cells, the actin cytoskeleton, and intracellular signaling
      pathways in a variety of cell types throughout the Metazoa. However, the full
      inventory of the proteins and pathways required for cadherin-mediated adhesion
      has not been established. To this end, we completed a genome-wide (~14,000 genes)
      ribonucleic acid interference (RNAi) screen that targeted Ca(2+)-dependent
      adhesion in DE-cadherin-expressing Drosophila melanogaster S2 cells in suspension
      culture. This novel screen eliminated Ca(2+)-independent cell-cell adhesion,
      integrin-based adhesion, cell spreading, and cell migration. We identified 17
      interconnected regulatory hubs, based on protein functions and protein-protein
      interactions that regulate the levels of the core cadherin-catenin complex and
      coordinate cadherin-mediated cell-cell adhesion. Representative proteins from
      these hubs were analyzed further in Drosophila oogenesis, using targeted germline
      RNAi, and adhesion was analyzed in Madin-Darby canine kidney mammalian epithelial
      cell-cell adhesion. These experiments reveal roles for a diversity of cellular
      pathways that are required for cadherin function in Metazoa, including
      cytoskeleton organization, cell-substrate interactions, and nuclear and
      cytoplasmic signaling.

PMID- 24446485
TI  - MicroRNA expression patterns associated with hyperfunctioning and non
      hyperfunctioning phenotypes in adrenocortical adenomas.
AB  - BACKGROUND: The adrenocortical adenoma (ACA) entity includes aldosterone
      producing adenoma (APA), cortisol-producing adenoma (CPA), and non
      hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA
      expression profiles have been partly characterized, less is known about the
      alterations involving microRNA (miRNA) expression. AIM: To characterize miRNA
      expression profile in relation to the subtypes of ACAs. SUBJECTS AND METHODS:
      miRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and
      seven NHFAs) and four adrenal references using microarray-based screening.
      Significance analysis of microarrays (SAM) was carried out to identify
      differentially expressed miRNAs between ACA and adrenal cortices or between tumor
      subtypes. Selected differentially expressed miRNAs were validated in an extended
      series of 43 ACAs and ten adrenal references by quantitative RT-PCR. RESULTS: An
      hierarchical clustering revealed separate clusters for APAs and CPAs, while the
      NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded,
      the clustering analysis showed a better separation between APA and CPA. SAM
      analysis identified 40 over-expressed and three under-expressed miRNAs in the
      adenomas as compared with adrenal references. Fourteen miRNAs were common among
      the three ACA subtypes. Furthermore, we found specific miRNAs associated with
      different tumor phenotypes. CONCLUSION: The results suggest that miRNA expression
      profiles can distinguish different subtypes of ACA, which may contribute to a
      deeper understanding of ACA development and potential therapeutics.

PMID- 24446486
TI  - Parkin and PINK1 function in a vesicular trafficking pathway regulating
      mitochondrial quality control.
AB  - Mitochondrial dysfunction has long been associated with Parkinson's disease (PD).
      Parkin and PINK1, two genes associated with familial PD, have been implicated in
      the degradation of depolarized mitochondria via autophagy (mitophagy). Here, we
      describe the involvement of parkin and PINK1 in a vesicular pathway regulating
      mitochondrial quality control. This pathway is distinct from canonical mitophagy
      and is triggered by the generation of oxidative stress from within mitochondria.
      Wild-type but not PD-linked mutant parkin supports the biogenesis of a population
      of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a
      specific repertoire of cargo proteins. These MDVs require PINK1 expression and
      ultimately target to lysosomes for degradation. We hypothesize that loss of this
      parkin- and PINK1-dependent trafficking mechanism impairs the ability of
      mitochondria to selectively degrade oxidized and damaged proteins leading, over
      time, to the mitochondrial dysfunction noted in PD. 

PMID- 24446487
TI  - E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during
      pathogenesis.
AB  - Pathogenic bacteria introduce effector proteins directly into the cytosol of
      eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp.
      effector kinase, plays a role in this process by helping to suppress the host
      inflammatory response. OspG has been reported to bind host E2 ubiquitin
      conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in
      ubiquitin transfer pathways. A co-crystal structure of the OspG/UbcH5c~Ub complex
      reveals that complex formation has important ramifications for the activity of
      both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing
      only essential elements required for catalysis. UbcH5c~Ub binding stabilizes an
      active conformation of the kinase, greatly enhancing OspG kinase activity. In
      contrast, interaction with OspG stabilizes an extended, less reactive form of
      UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten
      distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub
      conjugates act as novel regulators of OspG effector kinase function in eukaryotic
      host cells. 

PMID- 24446488
TI  - Muller glia cells regulate Notch signaling and retinal angiogenesis via the
      generation of 19,20-dihydroxydocosapentaenoic acid.
AB  - Cytochrome P450 (CYP) epoxygenases generate bioactive lipid epoxides which can be
      further metabolized to supposedly less active diols by the soluble epoxide
      hydrolase (sEH). As the role of epoxides and diols in angiogenesis is unclear, we
      compared retinal vasculature development in wild-type and sEH(-/-) mice. Deletion
      of the sEH significantly delayed angiogenesis, tip cell, and filopodia formation,
      a phenomenon associated with activation of the Notch signaling pathway. In the
      retina, sEH was localized in Muller glia cells, and Muller cell-specific sEH
      deletion reproduced the sEH(-/-) retinal phenotype. Lipid profiling revealed that
      sEH deletion decreased retinal and Muller cell levels of 19,20
      dihydroxydocosapentaenoic acid (DHDP), a diol of docosahexenoic acid (DHA). 19,20
      DHDP suppressed endothelial Notch signaling in vitro via inhibition of the gamma
      secretase and the redistribution of presenilin 1 from lipid rafts. Moreover,
      19,20-DHDP, but not the parent epoxide, was able to rescue the defective
      angiogenesis in sEH(-/-) mice as well as in animals lacking the Fbxw7 ubiquitin
      ligase, which demonstrate strong basal activity of the Notch signaling cascade.
      These studies demonstrate that retinal angiogenesis is regulated by a novel form
      of neuroretina-vascular interaction involving the sEH-dependent generation of a
      diol of DHA in Muller cells. 

PMID- 24446490
TI  - Clonal expansion capacity defines two consecutive developmental stages of long
      term hematopoietic stem cells.
AB  - Long-term hematopoietic stem cells (HSCs [LT-HSCs]) are well known to display
      unpredictable differences in their clonal expansion capacities after
      transplantation. Here, by analyzing the cellular output after transplantation of
      stem cells differing in surface expression levels of the Kit receptor, we show
      that LT-HSCs can be systematically subdivided into two subtypes with distinct
      reconstitution behavior. LT-HSCs expressing intermediate levels of Kit receptor
      (Kit(int)) are quiescent in situ but proliferate extensively after
      transplantation and therefore repopulate large parts of the recipient's
      hematopoietic system. In contrast, metabolically active Kit(hi) LT-HSCs display
      more limited expansion capacities and show reduced but robust levels of
      repopulation after transfer. Transplantation into secondary and tertiary
      recipient mice show maintenance of efficient repopulation capacities of Kit(int)
      but not of Kit(hi) LT-HSCs. Initiation of differentiation is marked by the
      transit from Kit(int) to Kit(hi) HSCs, both of which precede any other known stem
      cell population. 

PMID- 24446489
TI  - Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in
      humans and mice to exacerbate pulmonary hypertension.
AB  - Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and
      potentially fatal disease linked to a mutation or reduced expression of bone
      morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory
      cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2
      enhances production of the potent chemokine granulocyte macrophage colony
      stimulating factor (GM-CSF) in response to an inflammatory perturbation. When
      human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated
      with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and
      related to enhanced messenger RNA (mRNA) translation. The mechanism was
      associated with disruption of stress granule formation. Specifically, loss of
      BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in
      response to TNF, and this increased GADD34-PP1 phosphatase activity,
      dephosphorylating eukaryotic translation initiation factor (eIF2alpha), and
      derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused
      donor controls revealed heightened PA expression of GM-CSF co-distributing with
      increased TNF and expanded populations of hematopoietic and endothelial GM-CSF
      receptor alpha (GM-CSFRalpha)-positive cells. Moreover, a 3-wk infusion of GM-CSF
      in mice increased hypoxia-induced PAH, in association with increased perivascular
      macrophages and muscularized distal arteries, whereas blockade of GM-CSF
      repressed these features. Thus, reduced BMPR2 can subvert a stress granule
      response, heighten GM-CSF mRNA translation, increase inflammatory cell
      recruitment, and exacerbate PAH. 

PMID- 24446491
TI  - High c-Kit expression identifies hematopoietic stem cells with impaired self
      renewal and megakaryocytic bias.
AB  - Hematopoietic stem cells (HSCs) are heterogeneous with respect to their self
      renewal, lineage, and reconstitution potentials. Although c-Kit is required for
      HSC function, gain and loss-of-function c-Kit mutants suggest that even small
      changes in c-Kit signaling profoundly affect HSC function. Herein, we demonstrate
      that even the most rigorously defined HSCs can be separated into functionally
      distinct subsets based on c-Kit activity. Functional and transcriptome studies
      show HSCs with low levels of surface c-Kit expression (c-Kit(lo)) and signaling
      exhibit enhanced self-renewal and long-term reconstitution potential compared
      with c-Kit(hi) HSCs. Furthermore, c-Kit(lo) and c-Kit(hi) HSCs are hierarchically
      organized, with c-Kit(hi) HSCs arising from c-Kit(lo) HSCs. In addition, whereas
      c-Kit(hi) HSCs give rise to long-term lymphomyeloid grafts, they exhibit an
      intrinsic megakaryocytic lineage bias. These functional differences between c
      Kit(lo) and c-Kit(hi) HSCs persist even under conditions of stress hematopoiesis
      induced by 5-fluorouracil. Finally, our studies show that the transition from c
      Kit(lo) to c-Kit(hi) HSC is negatively regulated by c-Cbl. Overall, these studies
      demonstrate that HSCs exhibiting enhanced self-renewal potential can be isolated
      based on c-Kit expression during both steady state and stress hematopoiesis.
      Moreover, they provide further evidence that the intrinsic functional
      heterogeneity previously described for HSCs extends to the megakaryocytic
      lineage. 

PMID- 24446492
TI  - Repositioning therapy for thyroid cancer: new insights on established
      medications.
AB  - Repositioning of established non-cancer pharmacotherapeutic agents with well
      known activity and side-effect profiles is a promising avenue for the development
      of new treatment modalities for multiple cancer types. We have analyzed some of
      the medications with mechanism of action that may have relevance to thyroid
      cancer (TC). Experimental in vitro and in vivo evidences, as well as results of
      clinical studies, have indicated that molecular targets for medications currently
      available for the treatment of mood disorders, sexually transmitted diseases,
      metabolic disorders, and diabetes may be active and relevant in TC. For instance,
      the derivatives of cannabis and an anti-diabetic agent, metformin, both are able
      to inhibit ERK, which is commonly activated in TC cells. We present here several
      examples of well-known medications that have the potential to become new
      therapeutics for patients with TC. Repositioning of established medications for
      the treatment of TC could broaden the scope of current therapeutic strategies.
      These diverse treatment choices could allow physicians to provide an
      individualized approach to optimize treatment for patients with TC. 

PMID- 24446493
TI  - What is all the noise about in interval timing?
AB  - Cognitive processes such as decision-making, rate calculation and planning
      require an accurate estimation of durations in the supra-second range-interval
      timing. In addition to being accurate, interval timing is scale invariant: the
      time-estimation errors are proportional to the estimated duration. The origin and
      mechanisms of this fundamental property are unknown. We discuss the computational
      properties of a circuit consisting of a large number of (input) neural
      oscillators projecting on a small number of (output) coincidence detector
      neurons, which allows time to be coded by the pattern of coincidental activation
      of its inputs. We showed analytically and checked numerically that time-scale
      invariance emerges from the neural noise. In particular, we found that errors or
      noise during storing or retrieving information regarding the memorized criterion
      time produce symmetric, Gaussian-like output whose width increases linearly with
      the criterion time. In contrast, frequency variability produces an asymmetric,
      long-tailed Gaussian-like output, that also obeys scale invariant property. In
      this architecture, time-scale invariance depends neither on the details of the
      input population, nor on the distribution probability of noise. 

PMID- 24446495
TI  - Time-based reward maximization.
AB  - Humans and animals time intervals from seconds to minutes with high accuracy but
      limited precision. Consequently, time-based decisions are inevitably subjected to
      our endogenous timing uncertainty, and thus require temporal risk assessment. In
      this study, we tested temporal risk assessment ability of humans when
      participants had to withhold each subsequent response for a minimum duration to
      earn reward and each response reset the trial time. Premature responses were not
      penalized in Experiment 1 but were penalized in Experiment 2. Participants tried
      to maximize reward within a fixed session time (over eight sessions) by pressing
      a key. No instructions were provided regarding the task rules/parameters. We
      evaluated empirical performance within the framework of optimality that was based
      on the level of endogenous timing uncertainty and the payoff structure.
      Participants nearly tracked the optimal target inter-response times (IRTs) that
      changed as a function of the level of timing uncertainty and maximized the reward
      rate in both experiments. Acquisition of optimal target IRT was rapid and abrupt
      without any further improvement or worsening. These results constitute an example
      of optimal temporal risk assessment performance in a task that required finding
      the optimal trade-off between the 'speed' (timing) and 'accuracy' (reward
      probability) of timed responses for reward maximization. 

PMID- 24446494
TI  - Timing as an intrinsic property of neural networks: evidence from in vivo and in
      vitro experiments.
AB  - The discrimination and production of temporal patterns on the scale of hundreds
      of milliseconds are critical to sensory and motor processing. Indeed, most
      complex behaviours, such as speech comprehension and production, would be
      impossible in the absence of sophisticated timing mechanisms. Despite the
      importance of timing to human learning and cognition, little is known about the
      underlying mechanisms, in particular whether timing relies on specialized
      dedicated circuits and mechanisms or on general and intrinsic properties of
      neurons and neural circuits. Here, we review experimental data describing timing
      and interval-selective neurons in vivo and in vitro. We also review theoretical
      models of timing, focusing primarily on the state-dependent network model, which
      proposes that timing in the subsecond range relies on the inherent time-dependent
      properties of neurons and the active neural dynamics within recurrent circuits.
      Within this framework, time is naturally encoded in populations of neurons whose
      pattern of activity is dynamically changing in time. Together, we argue that
      current experimental and theoretical studies provide sufficient evidence to
      conclude that at least some forms of temporal processing reflect intrinsic
      computations based on local neural network dynamics. 

PMID- 24446496
TI  - Zebrafish forebrain and temporal conditioning.
AB  - The rise of zebrafish as a neuroscience research model organism, in conjunction
      with recent progress in single-cell resolution whole-brain imaging of larval
      zebrafish, opens a new window of opportunity for research on interval timing. In
      this article, we review zebrafish neuroanatomy and neuromodulatory systems, with
      particular focus on identifying homologies between the zebrafish forebrain and
      the mammalian forebrain. The neuroanatomical and neurochemical basis of interval
      timing is summarized with emphasis on the potential of using zebrafish to reveal
      the neural circuits for interval timing. The behavioural repertoire of larval
      zebrafish is reviewed and we demonstrate that larval zebrafish are capable of
      expecting a stimulus at a precise time point with minimal training. In
      conclusion, we propose that interval timing research using zebrafish and whole
      brain calcium imaging at single-cell resolution will contribute to our
      understanding of how timing and time perception originate in the vertebrate brain
      from the level of single cells to circuits. 

PMID- 24446497
TI  - Prospective and retrospective duration memory in the hippocampus: is time in the
      foreground or background?
AB  - Psychologists have long distinguished between prospective and retrospective
      timing to highlight the difference between our sense of duration during an
      experience in passing and our sense of duration in hindsight. Humans and other
      animals use prospective timing in the seconds-to-minutes range in order to learn
      durations, and can organize their behaviour based upon this knowledge when they
      know that duration information will be important ahead of time. By contrast, when
      durations are estimated after the fact, thus precluding the subject from
      consciously attending to temporal information, duration information must be
      extracted from other memory representations. The accumulated evidence from
      prospective timing research has generally led to the hippocampus (HPC) being
      casted in a supporting role with prefrontal-striatal, cortical or cerebellar
      circuits playing the lead. Here, I review findings from the animal and human
      literature that have led to this conclusion and consider that the contribution of
      the HPC to duration memory is understated because we have little understanding
      about how we remember duration. 

PMID- 24446498
TI  - Cognitive assessment of mice strains heterozygous for cell-adhesion genes reveals
      strain-specific alterations in timing.
AB  - We used a fully automated system for the behavioural measurement of
      physiologically meaningful properties of basic mechanisms of cognition to test
      two strains of heterozygous mutant mice, Bfc (batface) and L1, and their wild
      type littermate controls. Both of the target genes are involved in the
      establishment and maintenance of synapses. We find that the Bfc heterozygotes
      show reduced precision in their representation of interval duration, whereas the
      L1 heterozygotes show increased precision. These effects are functionally
      specific, because many other measures made on the same mice are unaffected,
      namely: the accuracy of matching temporal investment ratios to income ratios in a
      matching protocol, the rate of instrumental and classical conditioning, the
      latency to initiate a cued instrumental response, the trials on task and the
      impulsivity in a switch paradigm, the accuracy with which mice adjust timed
      switches to changes in the temporal constraints, the days to acquisition, and
      mean onset time and onset variability in the circadian anticipation of food
      availability. 

PMID- 24446499
TI  - Minutes, days and years: molecular interactions among different scales of
      biological timing.
AB  - Biological clocks are genetically encoded oscillators that allow organisms to
      keep track of their environment. Among them, the circadian system is a highly
      conserved timing structure that regulates several physiological, metabolic and
      behavioural functions with periods close to 24 h. Time is also crucial for
      everyday activities that involve conscious time estimation. Timing behaviour in
      the second-to-minutes range, known as interval timing, involves the interaction
      of cortico-striatal circuits. In this review, we summarize current findings on
      the neurobiological basis of the circadian system, both at the genetic and
      behavioural level, and also focus on its interactions with interval timing and
      seasonal rhythms, in order to construct a multi-level biological clock. 

PMID- 24446500
TI  - Comparison of interval timing behaviour in mice following dorsal or ventral
      hippocampal lesions with mice having delta-opioid receptor gene deletion.
AB  - Mice with cytotoxic lesions of the dorsal hippocampus (DH) underestimated 15 s
      and 45 s target durations in a bi-peak procedure as evidenced by proportional
      leftward shifts of the peak functions that emerged during training as a result of
      decreases in both 'start' and 'stop' times. In contrast, mice with lesions of the
      ventral hippocampus (VH) displayed rightward shifts that were immediately present
      and were largely limited to increases in the 'stop' time for the 45 s target
      duration. Moreover, the effects of the DH lesions were congruent with the scalar
      property of interval timing in that the 15 s and 45 s functions superimposed when
      plotted on a relative timescale, whereas the effects of the VH lesions violated
      the scalar property. Mice with DH lesions also showed enhanced reversal learning
      in comparison to control and VH lesioned mice. These results are compared with
      the timing distortions observed in mice lacking delta-opioid receptors (Oprd1(-/
      )) which were similar to mice with DH lesions. Taken together, these results
      suggest a balance between hippocampal-striatal interactions for interval timing
      and demonstrate possible functional dissociations along the septotemporal axis of
      the hippocampus in terms of motivation, timed response thresholds and encoding in
      temporal memory. 

PMID- 24446501
TI  - Reading spike timing without a clock: intrinsic decoding of spike trains.
AB  - The precise timing of action potentials of sensory neurons relative to the time
      of stimulus presentation carries substantial sensory information that is lost or
      degraded when these responses are summed over longer time windows. However, it is
      unclear whether and how downstream networks can access information in precise
      time-varying neural responses. Here, we review approaches to test the hypothesis
      that the activity of neural populations provides the temporal reference frames
      needed to decode temporal spike patterns. These approaches are based on comparing
      the single-trial stimulus discriminability obtained from neural codes defined
      with respect to network-intrinsic reference frames to the discriminability
      obtained from codes defined relative to the experimenter's computer clock.
      Application of this formalism to auditory, visual and somatosensory data shows
      that information carried by millisecond-scale spike times can be decoded robustly
      even with little or no independent external knowledge of stimulus time. In
      cortex, key components of such intrinsic temporal reference frames include
      dedicated neural populations that signal stimulus onset with reliable and precise
      latencies, and low-frequency oscillations that can serve as reference for
      partitioning extended neuronal responses into informative spike patterns. 

PMID- 24446502
TI  - Timing in reward and decision processes.
AB  - Sensitivity to time, including the time of reward, guides the behaviour of all
      organisms. Recent research suggests that all major reward structures of the brain
      process the time of reward occurrence, including midbrain dopamine neurons,
      striatum, frontal cortex and amygdala. Neuronal reward responses in dopamine
      neurons, striatum and frontal cortex show temporal discounting of reward value.
      The prediction error signal of dopamine neurons includes the predicted time of
      rewards. Neurons in the striatum, frontal cortex and amygdala show responses to
      reward delivery and activities anticipating rewards that are sensitive to the
      predicted time of reward and the instantaneous reward probability. Together these
      data suggest that internal timing processes have several well characterized
      effects on neuronal reward processing. 

PMID- 24446503
TI  - Towards an integrated understanding of the biology of timing.

PMID- 24446504
TI  - Parent-of-origin genetic background affects the transcriptional levels of
      circadian and neuronal plasticity genes following sleep loss.
AB  - Sleep homoeostasis refers to a process in which the propensity to sleep increases
      as wakefulness progresses and decreases as sleep progresses. Sleep is tightly
      organized around the circadian clock and is regulated by genetic and epigenetic
      mechanisms. The homoeostatic response of sleep, which is classically triggered by
      sleep deprivation, is generally measured as a rebound effect of
      electrophysiological measures, for example delta sleep. However, more recently,
      gene expression changes following sleep loss have been investigated as biomarkers
      of sleep homoeostasis. The genetic background of an individual may affect this
      sleep-dependent gene expression phenotype. In this study, we investigated whether
      parental genetic background differentially modulates the expression of genes
      following sleep loss. We tested the progeny of reciprocal crosses of AKR/J and
      DBA/2J mouse strains and we show a parent-of-origin effect on the expression of
      circadian, sleep and neuronal plasticity genes following sleep deprivation. Thus,
      we further explored, by in silico, specific functions or upstream mechanisms of
      regulation and we observed that several upstream mechanisms involving signalling
      pathways (i.e. DICER1, PKA), growth factors (CSF3 and BDNF) and transcriptional
      regulators (EGR2 and ELK4) may be differentially modulated by parental effects.
      This is the first report showing that a behavioural manipulation (e.g. sleep
      deprivation) in adult animals triggers specific gene expression responses
      according to parent-of-origin genomic mechanisms. Our study suggests that the
      same mechanism may be extended to other behavioural domains and that the
      investigation of gene expression following experimental manipulations should take
      seriously into account parent-of-origin effects. 

PMID- 24446505
TI  - Relative timing: from behaviour to neurons.
AB  - Processing of temporal information is critical to behaviour. Here, we review the
      phenomenology and mechanism of relative timing, ordinal comparisons between the
      timing of occurrence of events. Relative timing can be an implicit component of
      particular brain computations or can be an explicit, conscious judgement.
      Psychophysical measurements of explicit relative timing have revealed clues about
      the interaction of sensory signals in the brain as well as in the influence of
      internal states, such as attention, on those interactions. Evidence from human
      neurophysiological and functional imaging studies, neuropsychological examination
      in brain-lesioned patients, and temporary disruptive interventions such as
      transcranial magnetic stimulation (TMS), point to a role of the parietal cortex
      in relative timing. Relative timing has traditionally been modelled as a 'race'
      between competing neural signals. We propose an updated race process based on the
      integration of sensory evidence towards a decision threshold rather than simple
      signal propagation. The model suggests a general approach for identifying brain
      regions involved in relative timing, based on looking for trial-by-trial
      correlations between neural activity and temporal order judgements (TOJs).
      Finally, we show how the paradigm can be used to reveal signals related to TOJs
      in parietal cortex of monkeys trained in a TOJ task. 

PMID- 24446506
TI  - Action, time and the basal ganglia.
AB  - The ability to control the speed of movement is compromised in neurological
      disorders involving the basal ganglia, a set of subcortical cerebral nuclei that
      receive prominent dopaminergic projections from the midbrain. For example,
      bradykinesia, slowness of movement, is a major symptom of Parkinson's disease,
      whereas rapid tics are observed in patients with Tourette syndrome. Recent
      experimental work has also implicated dopamine (DA) and the basal ganglia in
      action timing. Here, I advance the hypothesis that the basal ganglia control the
      rate of change in kinaesthetic perceptual variables. In particular, the
      sensorimotor cortico-basal ganglia network implements a feedback circuit for the
      control of movement velocity. By modulating activity in this network, DA can
      change the gain of velocity reference signals. The lack of DA thus reduces the
      output of the velocity control system which specifies the rate of change in body
      configurations, slowing the transition from one body configuration to another. 

PMID- 24446508
TI  - Measurement of air kerma rates for 6- to 7-MeV high-energy gamma-ray field by
      ionisation chamber and build-up plate.
AB  - The 6- to 7-MeV high-energy gamma-ray calibration field by the (19)F(p,
      alphagamma)(16)O reaction is to be served at the Japan Atomic Energy Agency. For
      the determination of air kerma rates using an ionisation chamber in the 6- to 7
      MeV high-energy gamma-ray field, the establishment of the charged particle
      equilibrium must be achieved during measurement. In addition to measurement of
      air kerma rates by the ionisation chamber with a thick build-up cap, measurement
      using the ionisation chamber and a build-up plate (BUP) was attempted, in order
      to directly determine air kerma rates under the condition of regular calibration
      for ordinary survey meters and personal dosemeters. Before measurements, Monte
      Carlo calculations were made to find the optimum arrangement of BUP in front of
      the ionisation chamber so that the charged particle equilibrium could be well
      established. Measured results imply that air kerma rates for the 6- to 7-MeV high
      energy gamma-ray field could be directly determined under the appropriate
      condition using an ionisation chamber coupled with build-up materials. 

PMID- 24446507
TI  - On the regulation and function of secondary metabolism during fruit development
      and ripening.
AB  - The maturation and development of tomato fruit has received much attention due
      both to the complexity and intricacy of the changes which occur during this
      process and to the importance of these fruits as a component of the human diet.
      Whilst great advances have been made in understanding molecular genetic aspects
      of fruit development, our knowledge concerning the metabolic shifts underpinning
      this process remains largely confined to primary metabolism. Conversely, the
      majority of the metabolites considered to have health benefits are secondary or
      specialized metabolites. Prior to assessing the role (if any) of these
      metabolites in tomato fruit development, considerable effort will be required in
      order to better describe the complement of secondary metabolites in the tomato
      and to elucidate the metabolic pathways involved in their synthesis and
      degradation. Advances in tomato secondary metabolism will be reviewed here
      focusing on the use of metabolomics strategies and, where applicable, the
      enabling of these strategies by their coupling to information resident in the
      tomato genome sequence. 

PMID- 24446509
TI  - Amiodarone reduces the amount of ablation during catheter ablation for persistent
      atrial fibrillation.
AB  - AIMS: The step-wise approach to catheter ablation for persistent atrial
      fibrillation (AF) requires considerable substrate modification targeting at
      complex fractionated atrial electrograms (CFAEs) in addition to pulmonary vein
      (PV) isolation. An alternative strategy that minimizes the amount of ablation
      would be desirable. The aim of this study was to investigate whether the use of
      pre-procedural amiodarone affects: (i) the amount of ablation required to achieve
      procedural success, and (ii) long-term outcomes. METHODS AND RESULTS: We studied
      121 consecutive patients with persistent AF who underwent catheter ablation. The
      patients were divided into two groups: Group 1, amiodarone (n = 31); Group 2,
      other antiarrhythmic drugs or rate control (n = 90). All the patients underwent a
      step-wise ablation procedure beginning with PV isolation, then proceeding with
      ablation of the CFAEs and linear lesions until sinus rhythm was achieved. Mean
      left atrial cycle length of AF (AFCL) was recorded at each step. The number of
      CFAE ablation sites was recorded. The number of CFAE sites in Group 1 was
      significantly less than that in Group 2 (P = 0.0121). The AFCLs after each step
      in Group 1 were significantly longer than those in Group 2. The procedure time
      and the radiofrequency time of CFAE ablation in Group 1 were significantly
      shorter than that in Group 2 (P = 0.0276 and P = 0.0458, respectively). There was
      no significant difference between the two groups in early and long-term outcomes.
      CONCLUSION: Use of pre-procedural amiodarone prolongs AFCL during catheter
      ablation and reduces the number of CFAE sites requiring ablation to achieve
      procedural success while maintaining equivalent long-term results.

PMID- 24446510
TI  - Incidence of cerebral thromboembolic events during long-term follow-up in
      patients treated with transcatheter ablation for atrial fibrillation.
AB  - AIMS: Net clinical benefit of long-term oral anticoagulation therapy (OAT)
      continuation after successful atrial fibrillation (AF) ablation is still
      controversial. To evaluate long-term thromboembolic (TE) and haemorrhagic events
      incidence according to OAT strategy used after AF transcatheter ablation. METHODS
      AND RESULTS: Three months after AF ablation, OAT was discontinued in patients
      with CHADS2 <= 1 if no recurrences were documented, while OAT was maintained in
      patients with CHADS2 >= 2 regardless of AF recurrences. CHA2DS2VASc and HAS-BLED
      scores have been retrospectively evaluated. Seven hundred and sixty-six patients
      were followed for a median of 60.5 months. Six (6/267 = 2.2%) and five (5/499 =
      1%) TE events occurred in the ON and the OFF-OAT patients, respectively (P =
      0.145), all in concomitance with the AF recurrence. CHADS2 and CHA2DS2VASc >= 2
      were associated with high TE incidence (P = 0.047 and P = 0.020). Among patients
      with a CHADS2 score of 0 or 1, a CHA2DS2VASc score >= 2 was predictive of TE
      events (P = 0.014). Overall, the incidence of the TE events in patients with
      CHA2DS2VASc >= 2 was 0.6 per 100 patient-years whereas seven haemorrhagic events
      occurred, all of them in the ON-OAT patients (7/267 = 2.6%). CONCLUSION: Patients
      with AF undergoing transcatheter ablation have a lower incidence of TE events as
      compared with the general AF population, regardless of OAT maintenance. The
      unpredictable risk of AF recurrence, mandate the routine use of the CHADS2,
      CHA2DS2VASc, and HAS-BLED scores to guide clinical decision regarding OAT
      management in this peculiar setting of patients. The potential protective role of
      rhythm control strategy in the TE events needs to be confirmed by future large
      randomized trials.

PMID- 24446511
TI  - Improved lesion formation using the novel 28 mm cryoballoon in atrial
      fibrillation ablation: analysis of biomarker release.
AB  - AIMS: Recently, a novel second-generation (G2) cryoballoon (CB) was introduced.
      Comparative analysis of lesion formation in terms of myocardial biomarker release
      [first-generation CB (G1) vs. G2] has not been studied. To compare myocardial
      biomarker release using the 28 mm G1 vs. G2 CB. METHODS AND RESULTS: In patients
      (patients) treated with the simplified single big CB (SBCB) strategy for
      pulmonary vein isolation (PVI), myocardial biomarkers [troponin T (TnT), creatine
      kinase, lactic dehydrogenase (LDH)] were measured at 12, 24, and 48 h after PVI.
      Two groups were defined: Group 1 (G1; freezing time: 300 s), Group 2 (G2;
      freezing time: 240 s). Mean biomarker peak values were compared. To correct for
      between-group differences in cumulative freezing time, an index calculated as
      peak biomarker release divided by cumulative freezing time was calculated. Sixty
      six CB PVI procedures (G1: 33 patients, G2: 33 patients) were analysed. Pulmonary
      vein isolation was achieved in all the patients using the simplified SBCB
      technique only. Mean freezing time (51 +/- 10 vs. 33 +/- 6 min, P < 0.01) was
      significantly shorter in G2. All biomarker levels tended to be higher in G2 vs.
      G1. The indexed biomarkers values were significantly higher in G2: TnT: 18.8 +/-
      8.5 vs. 32.3 +/- 13.6 pg/L/min (P < 0.01); creatinephosphokinase: 6.7 +/- 2.7 vs.
      11.7 +/- 3.9 U/L/min (P < 0.01); LDH: 5.2 +/- 1.0 vs. 9.1 +/- 2.7 U/L/min (P <
      0.01). On a 6-month follow-up (180 days), G2 revealed a significantly higher
      success rate (20/33 vs. 28/33; P = 0.027). CONCLUSION: Pulmonary vein isolation
      using the G2 CB increased the myocardial biomarker release index and is linked to
      a significantly improved 6 months success rate.

PMID- 24446512
TI  - Ventricular fibrillation associated with multi-vessel coronary spasms following
      radiofrequency ablation of atrial fibrillation and atrial flutter.

PMID- 24446513
TI  - Dual-chamber pacemaker implantation with left ventricular pacing in a patient
      with a right ventricular assist device.

PMID- 24446514
TI  - Role of Th1/Th17 balance regulated by T-bet in a mouse model of Mycobacterium
      avium complex disease.
AB  - Th1 immune responses are thought to be important in protection against
      intracellular pathogens. T-bet is a critical regulator for Th1 cell
      differentiation and Th1 cytokine production. The aim of this study was to
      determine the role of T-bet in host defense against Mycobacterium avium complex
      (MAC) infection. Wild-type mice, T-bet-deficient mice, and T-bet-overexpressing
      mice were infected with MAC via intratracheal inoculation. Macrophages and
      dendritic cells obtained from these mice were incubated with MAC. T-bet-deficient
      mice were highly susceptible to MAC, compared with wild-type mice and T-bet
      overexpressing mice. Neutrophilic pulmonary inflammation was also enhanced in T
      bet-deficient mice, but attenuated in T-bet-overexpressing mice, following MAC
      infection. Cytokine expression shifted toward Th1 in the lung and spleen of T-bet
      overexpressing mice, but toward Th17 in T-bet-deficient mice. IFN-gamma
      supplementation to T-bet-deficient mice reduced systemic MAC growth but did not
      reduce pulmonary inflammation. In contrast, neutralization of IL-17 in T-bet
      deficient mice reduced pulmonary inflammation but did not affect mycobacterial
      growth in any organs tested. T-bet-deficient T cells tended to differentiate
      toward Th17 cells in vitro following exposure to MAC. Treatment with NO donor
      suppressed MAC-induced Th17 cell differentiation of T-bet-deficient T cells. This
      study identified that the fine balance between Th1 and Th17 responses is
      essential in defining the outcome of MAC disease. T-bet functions as a regulator
      for Th1/Th17 balance and is a critical determinant for host resistance to MAC
      infection by controlling cytokine and NO levels. 

PMID- 24446515
TI  - Mechanism of neutrophil dysfunction: neutrophil serine proteases cleave and
      inactivate the C5a receptor.
AB  - Neutrophil dysfunction, resulting in inefficient bacterial clearance, is a
      feature of several serious medical conditions, including cystic fibrosis (CF) and
      sepsis. Poorly controlled neutrophil serine protease (NSP) activity and
      complement activation have been implicated in this phenomenon. The capacity for
      excess NSP secretion and complement activation to influence the expression and
      function of the important neutrophil-activating receptor C5aR was investigated.
      Purified NSPs cathepsin G (CG), neutrophil elastase (NE), and proteinase 3
      cleaved C5aR to a 26- to 27-kDa membrane-bound fragment, thereby inactivating its
      C5a-induced signaling ability. In a supernatant transfer assay, NSPs released
      from neutrophils in response to C5a induced the cleavage of the C5aR on
      unstimulated cells. Stimulation of myeolomonocytic U937 cells and purified
      neutrophils with C5a resulted in downregulation of the C5aR on these cells,
      which, in the case of U937 cells, was largely caused by NSP-mediated cleavage of
      C5aR, but in the case of neutrophils, intracellular degradation was likely the
      main mediator in addition to a small role for NSPs. CG and NE in bronchoalveolar
      lavage fluid from CF patients both contributed to C5aR cleavage. We propose two
      converging models for C5a- and NSP-mediated neutrophil dysfunction whereby C5aR
      cleavage is induced by NSPs, secreted in response to: 1) excess C5a generation or
      other stimuli; or 2) necrosis. The consequent impairment of C5aR activity
      contributes to suboptimal local neutrophil priming and bacterial clearance. NSP
      inhibitors with specificity for both CG and NE may aid the treatment of
      pathologies associated with neutrophil dysfunction including sepsis and CF. 

PMID- 24446516
TI  - IL-21 contributes to fatal inflammatory disease in the absence of Foxp3+ T
      regulatory cells.
AB  - The cytokine IL-21 has been shown to influence immune responses through both
      costimulatory effects on effector T cells and opposing inhibitory effects on T
      regulatory cells (Tregs). To distinguish the effect of IL-21 on the immune system
      from that of its effect on Tregs, we analyzed the role of IL-21/IL-21R signaling
      in mice made genetically deficient in IL-2, which exhibit a deficit in IL-2
      dependent Foxp3 regulatory T cells and suffer from a fatal multiorgan
      inflammatory disease. Our findings demonstrate that in the absence of IL-21/IL
      21R signaling, Il2(-/-) mice retained a deficiency in Tregs yet exhibited a
      reduced and delayed inflammatory disease. The improved health of Il2(-/-)Il21r(-/
      ) mice was reflected in reduced pancreatitis and hemolytic anemia and this was
      associated with distinct changes in lymphocyte effector populations, including
      the reduced expansion of both T follicular helper cells and Th17 cells and a
      compensatory increase in IL-22 in the absence of IL-21R. IL-21/IL-21R
      interactions were also important for the expansion of effector and memory CD8(+)
      T cells, which were critical for the development of pancreatitis in Il2(-/-)
      mice. These findings demonstrate that IL-21 is a major target of immune system
      regulation. 

PMID- 24446517
TI  - Islet antigen-specific Th17 cells can induce TNF-alpha-dependent autoimmune
      diabetes.
AB  - Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic beta
      cells. Although Th1 cells are key orchestrators of T1D, the function(s) of the
      more recently identified Th17 subset are unclear due to inherent plasticity. In
      this study, we analyzed Th17 cells for stability and diabetogenicity in NOD mice.
      We found that like Th1 cells, Th17 are a distinct population throughout the
      prediabetic phase. At diabetes onset, there were marked increases in IL-17
      producing Th17 cells and IFN-gamma-producing Th1 cells in the pancreas as well as
      in the serum levels of these cytokines, indicating that these proinflammatory
      mediators serve as biomarkers of advanced autoimmunity. Although naturally
      occurring Th17 cells in diabetic mice did not contribute to diabetes development
      in transfer models, islet-specific Th17 cells were diabetogenic independently of
      IL-17 and displayed inflammation-induced Th17-to-Th1 reprogramming that could be
      elicited by Th1 cells. However, an inability to generate Th1 cells because of
      Stat4, Ifngr, and Ifng deficiencies did not prevent diabetes. Instead, TNF-alpha
      could mediate diabetes in response to either Th17 cells or Th1 cells. The results
      identify a previously unknown mechanism by which Th17 cells can contribute to
      T1D. Our studies also suggest that when developing interventions for T1D, it will
      be potentially advantageous to focus on mechanisms common to effector T cells
      rather than on the signature cytokines of various subsets. 

PMID- 24446518
TI  - IL-17A promotes the exacerbation of IL-33-induced airway hyperresponsiveness by
      enhancing neutrophilic inflammation via CXCR2 signaling in mice.
AB  - Neutrophilic airway inflammation is a hallmark of patients with severe asthma.
      Although we have reported that both IL-33 and IL-17A contributed to IgE-mediated
      neutrophilic inflammation in mice, the relationship remains unclear. In this
      article, we examined how IL-17A modifies IL-33-induced neutrophilic inflammation
      and airway hyperresponsiveness (AHR). IL-33 was intratracheally administered to
      BALB/c mice on days 0-2; furthermore, on day 7, the effect of the combination of
      IL-33 and IL-17A was evaluated. Compared with IL-33 or IL-17A alone, the
      combination exacerbated neutrophilic inflammation and AHR, associated with more
      increased levels of lung glutamic acid-leucine-arginine(+) CXC chemokines,
      including CXCL1, CXCL2, and CXCL5, and infiltration by alveolar macrophages
      expressing CXCR2. Treatment with anti-CXCR2 mAb or depletion of alveolar
      macrophages repressed neutrophilic inflammation and AHR; in addition, depletion
      of neutrophils suppressed AHR. These findings prompted us to examine the role of
      CXCR2 in IgE-sensitized mice; a single treatment with anti-CXCR2 mAb in the
      seventh Ag challenge inhibited late-phase airway obstruction, AHR, and
      neutrophilic inflammation. In addition to inhibition, multiple treatments during
      the fourth to seventh challenge attenuated early-phase airway obstruction,
      eosinophilic inflammation, and goblet cell hyperplasia associated with the
      reduction of Th2 cytokine production, including IL-4, IL-5, and IL-13.
      Collectively, IL-33 cooperated with IL-17A to exacerbate AHR by enhancing
      neutrophilic inflammation via CXCR2 signaling; furthermore, CXCR2 signaling
      derived Th2 responses. We thus suggest the underlying mechanisms of IL-33 and IL
      17A in allergic asthma and CXCR2 as potential therapeutic targets for the
      disease. 

PMID- 24446519
TI  - CD8+ T cells are activated in an antigen-independent manner in HIV-infected
      individuals.
AB  - Hyperactivation of T cells, particularly of CD8(+) T cells, is a hallmark of
      chronic HIV 1 (HIV-1) infection. Little is known about the antigenic
      specificities and the mechanisms by which HIV-1 causes activation of CD8(+) T
      cells during chronic infection. We report that CD8(+) T cells were activated
      during in vivo HIV-1 replication irrespective of their Ag specificity. Cytokines
      present during untreated HIV-1 infection, most prominently IL-15, triggered
      proliferation and expression of activation markers in CD8(+) T cells, but not
      CD4(+) T cells, in the absence of TCR stimulation. Moreover, LPS or HIV-1
      activated dendritic cells (DCs) stimulated CD8(+) T cells in an IL-15-dependent
      but Ag-independent manner, and IL-15 expression was highly increased in DCs
      isolated from viremic HIV-1 patients, suggesting that CD8(+) T cells are
      activated by inflammatory cytokines in untreated HIV-1 patients independent of Ag
      specificity. This finding contrasts with CD4(+) T cells whose in vivo activation
      seems biased toward specificities for persistent Ags. These observations explain
      the higher abundance of activated CD8(+) T cells compared with CD4(+) T cells in
      untreated HIV-1 infection. 

PMID- 24446521
TI  - Streptococcus suis adenosine synthase functions as an effector in evasion of PMN
      mediated innate immunit.
AB  - Streptococcus suis serotype 2 (S. suis 2) is a highly invasive pathogen in pigs
      and humans that can cause severe systemic infection. Sepsis and meningitis are
      the most common clinical manifestations of S. suis 2 infection. However, the
      mechanisms of S. suis 2 surviving in human blood remains unclear, so to identify
      novel virulence factors in evasion of polymorphonuclear leukocyte (PMN)-mediated
      innate immunity play important roles in developing therapies against S. suis 2
      infection. Here, we found that S. suis 2 can escape phagocytic clearance by
      adenosine synthesis in blood. Through bioinformatics-based analyses we identified
      a cell wall-anchored protein harbors a 5'-nucleotidase signature sequence and
      evidence strongly indicated that it can convert adenosine monophosphate (AMP) to
      adenosine. It was designated as Ssads (the adenosine synthase of S. suis 2).
      Furthermore, we found that Ssads could impair PMN's defense against S. suis 2
      with decreasing of oxidative activity and degranulation of PMNs in human blood
      via A2a receptors. Additionally, this enzyme-deficient mutant was found to have
      diminished virulence in the piglet infection model. Taken together, these results
      indicate that Ssads play an important role in S. suis 2 escaping human innate
      immunity in the context of inhibiting PMN's activity by synthesis of adenosine.

PMID- 24446520
TI  - TNF-alpha-dependent hematopoiesis following Bcl11b deletion in T cells restricts
      metastatic melanoma.
AB  - Using several tumor models, we demonstrate that mice deficient in Bcl11b in T
      cells, although having reduced numbers of T cells in the peripheral lymphoid
      organs, developed significantly less tumors compared with wild-type mice. Bcl11b(
      /-) CD4(+) T cells, with elevated TNF-alpha levels, but not the Bcl11b(-/-)
      CD8(+) T cells, were required for the reduced tumor burden, as were NK1.1(+)
      cells, found in increased numbers in Bcl11b(F/F)/CD4-Cre mice. Among NK1.1(+)
      cells, the NK cell population was predominant in number and was the only
      population displaying elevated granzyme B levels and increased degranulation,
      although not increased proliferation. Although the number of myeloid-derived
      suppressor cells was increased in the lungs with metastatic tumors of
      Bcl11b(F/F)/CD4-Cre mice, their arginase-1 levels were severely reduced. The
      increase in NK cell and myeloid-derived suppressor cell numbers was associated
      with increased bone marrow and splenic hematopoiesis. Finally, the reduced tumor
      burden, increased numbers of NK cells in the lung, and increased hematopoiesis in
      Bcl11b(F/F)/CD4-Cre mice were all dependent on TNF-alpha. Moreover, TNF-alpha
      treatment of wild-type mice also reduced the tumor burden and increased
      hematopoiesis and the numbers and activity of NK cells in the lung. In vitro
      treatment with TNF-alpha of lineage-negative hematopoietic progenitors increased
      NK and myeloid differentiation, further supporting a role of TNF-alpha in
      promoting hematopoiesis. These studies reveal a novel role for TNF-alpha in the
      antitumor immune response, specifically in stimulating hematopoiesis and
      increasing the numbers and activity of NK cells. 

PMID- 24446522
TI  - One lesion, one virus: individual components of high-grade anal intraepithelial
      neoplasia in HIV-positive men contain a single HPV type.
AB  - BACKGROUND: High-grade anal intraepithelial neoplasia (AIN) is present in many
      human immunodeficiency virus (HIV)-positive men who have sex with men. The major
      etiologic factor is infection with an oncogenic human papillomavirus (HPV)
      genotype. We investigated whether individual components of high-grade AIN are
      caused by single HPV types. METHODS: DNA was isolated from whole-tissue sections
      of 31 high-grade AIN that were recovered from 21 HIV-positive men who have sex
      with men. The SPF10 PCR/LiPA25 HPV genotyping system was used for DNA analysis.
      In whole-tissue sections with multiple HPV types, polymerase chain reaction was
      repeated in regions of AIN sampled by laser-capture microdissection. The results
      were compared with HPV types in anal swabs. RESULTS: A single HPV type was
      observed in 15 (48%) of 31 whole-tissue sections. In an additional 14 whole
      tissue sections, 1 HPV type was found in each lesion sample evaluated by laser
      capture microdissection. Consequently, in 29 of 31 biopsy specimens (94%), a
      single HPV type was found in each lesional component studied. Two whole-tissue
      sections contained collision regions, each with 2 HPV types. HPV16 was presumed
      to be causative in 14 of 31 biopsy specimens (45%). More than half of the anal
      swabs did not contain all causative HPV types. CONCLUSIONS: Individual components
      of high-grade AIN are caused by single HPV types (the so-called one lesion, one
      virus concept). HPV16 is causative in <50% of cases. Anal swabs are not useful
      for detecting lesion-specific HPV types.

PMID- 24446524
TI  - Differential prevalence of transporter polymorphisms in symptomatic and
      asymptomatic falciparum malaria infections in Uganda.
AB  - We explored associations between Plasmodium falciparum drug resistance-mediating
      polymorphisms and clinical presentations in parasitemic children enrolled in a
      cross-sectional survey in Tororo, Uganda, using a retrospective case-control
      design. All 243 febrile children (cases) and 243 randomly selected asymptomatic
      children (controls) were included. In a multivariate analysis adjusting for age,
      complexity of infection, and parasite density, the prevalence of wild-type
      genotypes was significantly higher in febrile children compared to asymptomatic
      children (pfcrt K76T: odds ratio [OR] 4.41 [95% confidence interval {CI}, 1.28
      15.1]; pfmdr1 N86Y: OR 4.08 [95% CI, 2.01-8.31], and pfmdr1 D1246Y: OR 4.90 [95%
      CI, 1.52-15.8]), suggesting greater virulence for wild-type parasites.

PMID- 24446525
TI  - Multiyear persistence of 2 pandemic A/H1N1 influenza virus lineages in West
      Africa.
AB  - Our understanding of the global ecology of influenza viruses is impeded by
      historically low levels of viral surveillance in Africa. Increased genetic
      sequencing of African A/H1N1 pandemic influenza viruses during 2009-2013 revealed
      multiyear persistence of 2 viral lineages within West Africa, raising questions
      about the roles of reduced air traffic and the asynchrony of seasonal influenza
      epidemics among West African countries in the evolution of independent lineages.
      The potential for novel influenza virus lineages to evolve within Africa warrants
      intensified influenza surveillance in Africa and other understudied areas.

PMID- 24446526
TI  - Association of IL1B -31C/T and IL1RA variable number of an 86-bp tandem repeat
      with dengue shock syndrome in Thailand.
AB  - BACKGROUND: Dengue patients present a range of symptoms: dengue fever (DF),
      dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It is not clear
      whether this variability is due to their genetic background. Here we tested
      polymorphisms of interleukin 1 beta (IL1B) and interleukin 1 receptor antagonist
      (IL1RA) genes for association with DSS in the Thai population. METHODS:
      Polymorphisms of IL1B -31C/T (rs1143627) and IL1RA 86-base-pair tandem repeat
      were analyzed in 871 patients (DF = 384, DHF = 413, and DSS = 74). RESULTS: IL1B 
      31C and IL1RA 2/4 genotype were associated with DSS (IL1B -31C: DSS vs DHF: P =
      .0061, odds ratio [OR, 95% confidence interval {CI}], 3.49 [1.36-8.95]; DSS vs
      DF: P = .027, OR [95% CI], 2.81 [1.12-7.06]; IL1RA 2/4: DSS vs DHF: P = .017, OR
      [95% CI], 1.94 [1.12-3.40]; DSS vs DF: P = .024, OR [95% CI], 1.90 [1.07-3.4]).
      No difference was found between DF and DHF. Logistic regression analysis revealed
      that IL1B -31C and IL1RA 2/4 genotypes were each independently associated with
      DSS. CONCLUSIONS: Patients with IL1B -31C carrier, or IL1RA 2/4 genotype carry a
      risk for DSS, implying that IL1B may play a role in pathogenesis of DSS.

PMID- 24446523
TI  - Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or
      elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.
AB  - BACKGROUND: The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a
      human immunodeficiency virus (HIV) integrase inhibitor (INI), would be
      efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose.
      METHODS: VIKING-3 is a single-arm, open-label phase III study in which therapy
      experienced adults with INI-resistant virus received DTG 50 mg BID while
      continuing their failing regimen (without raltegravir or elvitegravir) through
      day 7, after which the regimen was optimized with >=1 fully active drug and DTG
      continued. The primary efficacy endpoints were the mean change from baseline in
      plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL
      at week 24. RESULTS: Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and
      69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated
      a strong association between baseline DTG susceptibility and response. Response
      was most reduced in subjects with Q148 + >=2 resistance-associated mutations. DTG
      50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to
      INI-naive subjects receiving DTG 50 mg once daily. CONCLUSIONS: DTG 50 mg BID
      based therapy was effective in this highly treatment-experienced population with
      INI-resistant virus. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov
      (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com
      (112574).

PMID- 24446528
TI  - Is there evidence for resistance of ocular Chlamydia trachomatis to azithromycin
      after mass treatment for trachoma control?
AB  - BACKGROUND: Trachoma, caused by repeated infections with ocular Chlamydia
      trachomatis, is targeted for elimination using multiple annual rounds of mass
      drug administration (MDA) in endemic communities. Infection rates do not decline
      as expected in some communities, leading to concerns about azithromycin
      resistance. METHODS: After 3 yearly MDAs in 32 communities in Tanzania, 107
      children were identified 1 year later with infection. All were provided MDA
      again, and 90 were seen again at 2 months, of whom 30 had infection. Chlamydia
      trachomatis isolates were obtained before and after MDA in 15 paired samples and
      were tested for antimicrobial susceptibility. The infectious load of C.
      trachomatis before MDA was determined in 30 children who had infection at both
      times and 60 whose infection cleared. RESULTS: The median load was 8.6 genome
      copies per polymerase chain reaction in the consistently infected, and 8.4 in
      those whose infection cleared (P = .86). For the consistently infected, the
      average minimum inhibitory concentration was 0.26 ug/mL for azithromycin before
      and 0.20 ug/mL after MDA. All isolates had minimum inhibitory concentration
      <=0.50 ug/mL. CONCLUSIONS: There is no evidence that continued infection after
      MDA was due either to resistance to azithromycin or to a heavier load of organism
      before treatment. Other potential causes of persistent infection need to be
      evaluated.

PMID- 24446527
TI  - Transferrin iron starvation therapy for lethal bacterial and fungal infections.
AB  - New strategies to treat antibiotic-resistant infections are urgently needed. We
      serendipitously discovered that stem cell conditioned media possessed broad
      antimicrobial properties. Biochemical, functional, and genetic assays confirmed
      that the antimicrobial effect was mediated by supra-physiological concentrations
      of transferrin. Human transferrin inhibited growth of gram-positive
      (Staphylococcus aureus), gram-negative (Acinetobacter baumannii), and fungal
      (Candida albicans) pathogens by sequestering iron and disrupting membrane
      potential. Serial passage in subtherapeutic transferrin concentrations resulted
      in no emergence of resistance. Infected mice treated with intravenous human
      transferrin had improved survival and reduced microbial burden. Finally,
      adjunctive transferrin reduced the emergence of rifampin-resistant mutants of S.
      aureus in infected mice treated with rifampin. Transferrin is a promising, novel
      antimicrobial agent that merits clinical investigation. These results provide
      proof of principle that bacterial infections can be treated in vivo by attacking
      host targets (ie, trace metal availability) rather than microbial targets. 

PMID- 24446530
TI  - Karl Jaspers: 100 years of General Psychopathology.

PMID- 24446529
TI  - Influenza A/subtype and B/lineage effectiveness estimates for the 2011-2012
      trivalent vaccine: cross-season and cross-lineage protection with unchanged
      vaccine.
AB  - BACKGROUND: We estimate vaccine effectiveness (VE) against both influenza
      A/subtypes and B/lineages in Canada for the 2011-2012 trivalent inactivated
      influenza vaccine (TIV) with components entirely unchanged from the 2010-2011 TIV
      and in the context of phenotypic and genotypic characterization of circulating
      viruses. METHODS: In a test-negative case-control study VE was estimated as [1
      (adjusted)OddsRatio] * 100 for RT-PCR-confirmed influenza in vaccinated vs
      nonvaccinated participants. Viruses were characterized by hemagglutination
      inhibition (HI) and sequencing of antigenic sites of the hemagglutinin (HA) gene.
      RESULTS: There were 1507 participants. VE against A(H1N1)pdm09 was 80% (95%
      confidence interval [CI], 52%-92%): circulating viruses were HI-characterized as
      vaccine-matched and bore just 2 aminoacid (AA) differences from vaccine. VE
      against A/H3N2 was 51% (95% CI, 10%-73%): circulating viruses were HI
      characterized as vaccine-related but bore >=11AA differences from vaccine. VE
      against influenza B was 51% (95% CI, 26%-67%) in total: 71% (95% CI, 40%-86%) for
      lineage-matched B/Victoria and 27% (95% CI, -21% to 56%) for lineage-mismatched
      B/Yamagata. For both influenza A and B types, VE was similar among recipients of
      either 2010-2011 or 2011-2012 TIV alone, higher when vaccinated both seasons.
      CONCLUSIONS: Phenotypic and genotypic characterization of circulating and vaccine
      viruses enhances understanding of TIV performance, shown in 2011-2012 to be
      substantial against well-conserved A(H1N1)pdm09 and lineage-matched influenza B,
      suboptimal against genetic-variants of A/H3N2, and further reduced against
      lineage-mismatched influenza B. With unchanged vaccine components, protection may
      extend beyond a single season.

PMID- 24446531
TI  - Hip-hop and psychiatry: a fair rap?

PMID- 24446532
TI  - Obsessive-compulsive disorder.

PMID- 24446534
TI  - RETRACTED: Ten years of experience with microsurgical treatment of large and
      giant petroclival meningiomas.

PMID- 24446533
TI  - [Suicide prevention: speech is golden].

PMID- 24446535
TI  - Report of Task Group on the implications of the implementation of the ICRP
      recommendations for a revised dose limit to the lens of the eye.
AB  - This report was commissioned by the IRPA President to provide an assessment of
      the impact on members of IRPA Associate Societies of the introduction of ICRP
      recommendations for a reduced dose limit for the lens of the eye. The report
      summarises current practice and considers possible changes that may be required.
      Recommendations for further collaboration, clarification and changes to working
      practices are suggested.

PMID- 24446536
TI  - Prediction of remission of depression with clinical variables, neuropsychological
      performance, and serotonergic/dopaminergic gene polymorphisms.
AB  - OBJECTIVE: The aim of our work is to study the possible role of clinical
      variables, neuropsychological performance, and the 5HTTLPR, rs25531, and
      val108/58Met COMT polymorphisms on the prediction of depression remission after
      12 weeks' treatment with fluoxetine. These variables have been studied as
      potential predictors of depression remission, but they present poor prognostic
      sensitivity and specificity by themselves. METHODS: Seventy-two depressed
      patients were genotyped according to the aforementioned polymorphisms and were
      clinically and neuropsychologically assessed before a 12-week fluxetine
      treatment. RESULTS: Only the La allele of rs25531 polymorphism and the GG and AA
      forms of the val 108/158 Met polymorphism predict major depressive disorder
      remission after 12 weeks' treatment with fluoxetine. None of the clinical and
      neuropsychological variables studied predicted remission. CONCLUSIONS: Our
      results suggest that clinical and neuropsychological variables can initially
      predict early response to fluoxetine and mask the predictive role of genetic
      variables; but in remission, where clinical and neuropsychological symptoms
      associated with depression tend to disappear thanks to the treatment
      administered, the polymorphisms studied are the only variables in our model
      capable of predicting remission. However, placebo effects that are difficult to
      control require cautious interpretation of the results.

PMID- 24446537
TI  - Next day effects of naturalistic alcohol consumption on tasks of attention.
AB  - OBJECTIVES: The aim of this study was to examine the next day effects of alcohol
      consumption on a range of attention tasks. METHODS: The study followed a
      counterbalanced repeated measure design, with participants tested the morning
      following normal/usual alcohol consumption and again the morning after no alcohol
      consumption. Participants were 48 social drinkers (15 men and 33 women), who
      performed attention tests at 9 am, 11 am, or 1 pm. Performance was assessed by
      tasks measuring sustained attention, divided attention, selective attention, and
      spatial attention and by the Stroop test. RESULTS: The morning after alcohol
      consumption, a significantly higher proportion of missed targets was observed
      (F(1, 40) = 6.43, p < 0.05) in the sustained attention task. In the Stroop test,
      participants responded significantly slower (F(1, 42) = 8.72, p < 0.005) in the
      interference condition (when naming the color of the ink of the words) the
      morning after alcohol consumption. In the selective attention task, the
      consumption of alcohol the night before eliminated the robust distance by
      compatibility interaction, which was observed the morning after no alcohol
      consumption (F(1, 43) = 10.41, p < 0.01). No influence of alcohol was observed in
      the divided attention test nor in the spatial attention task. CONCLUSION: Alcohol
      consumption has a negative impact on some but not all facets of attentional
      processing the morning after a normal nights drinking.

PMID- 24446538
TI  - The loudness dependence of auditory evoked potentials and effects of
      psychopathology and psychopharmacotherapy in psychiatric inpatients.
AB  - OBJECTIVE: Many studies have provided evidence for the loudness dependence of
      auditory evoked potentials (LDAEP) as a marker for central serotonergic activity
      but remained inconclusive for its suitability in clinical use. METHODS: A cross
      sectional sample of 162 psychiatric inpatients (major depression N = 86, bipolar
      disorder N = 12, schizophrenia N = 50, and schizoaffective disorder N = 14) and
      40 healthy subjects was retrospectively examined for LDAEP and effects of
      psychopathology and psychopharmacology. RESULTS: The LDAEP was weaker in patients
      with affective disorders than in healthy subjects but did not differentiate
      between the total patient sample and healthy controls. LDAEP correlated
      significantly with dimensions of the Brief Symptom Inventory in the total patient
      sample (depression, paranoid ideation, psychoticism, Global Symptom Index, and
      Positive Symptom Distress Index), in patients with affective disorders
      (depression) and with schizophrenia spectrum disorders (depression, psychoticism,
      Global Symptom Index, and Positive Symptom Distress Index). Similar correlations
      were found in depressed patients with a single noradrenergic and specific
      serotonergic antidepressant or serotonin-norepinephrine reuptake inhibitor. There
      was a negative correlation between dosage of typical antipsychotics and LDAEP.
      Hypnotics generally led to a lower LDAEP. CONCLUSION: The LDAEP in patients is
      related to severity of psychopathologic syndromes irrespective of diagnosis.
      Chronic psychopharmacologic treatment may also differentially modulate the LDAEP,
      but longitudinal studies are needed.

PMID- 24446539
TI  - Efficacy and metabolic influence of paliperidone ER, aripiprazole and ziprasidone
      to patients with first-episode schizophrenia through 52 weeks follow-up in China.
AB  - BACKGROUND: There are no direct comparisons of paliperidone extended-release
      (ER), aripiprazole and ziprasidone in efficacy and metabolic influence in
      patients with first-episode schizophrenia. OBJECTIVE: The present study examined
      the efficacy and metabolic influence of paliperidone ER, aripiprazole and
      ziprasidone in patients with first-episode schizophrenia in China. METHODS:
      Subjects were recruited from outpatient and 254 patients entered the trial. These
      patients received treatment randomly with paliperidone ER, aripiprazole and
      ziprasidone and were assessed at baseline, 13, 26 and 52 weeks, respectively with
      Positive and Negative Syndrome Scale (PANSS), 7-item Clinical Global Impressions
      Severity (CGI-S), anthropometric (weight, body mass index and waist
      circumference) and metabolic (fasting blood glucose, HbA1c, cholesterol, high
      density lipoproteins (HDL), low density lipoproteins and triglycerides) measures.
      RESULTS: A total of 203 patients completed the trial. Paliperidone group had
      significant greater reduction in PANSS than aripiprazole group and ziprasidone
      group from 13 weeks, although the a reduction in PANSS of each group was more
      than 20%. There was no difference in CGI-S among the three groups, and all three
      groups had a significant reduction from baseline in CGI-S. Aripiprazole group
      increased in weight and body mass index despite no statistical change in waist
      circumference. Other two groups showed no changes in anthropometric measure. At
      the end of the study, two glucose metabolic indices (fasting blood glucose and
      HbA1c) of aripiprazole group were significantly higher than that of baseline. In
      lipid metabolism, aripiprazole group reduced triglycerides significantly and had
      no changes in other indices. Paliperidone group reduced HDL and increased
      triglycerides despite no changes in glucose metabolism. Ziprasidone group also
      had no significant changes in glucose metabolism, but reduced cholesterol, low
      density lipoproteins and increased HDL. Furthermore, 22 subjects in three groups
      reached the diagnostic criteria of metabolic syndrome. CONCLUSIONS: Paliperidone
      ER, aripiprazole and ziprasidone are effective in treating first-episode
      schizophrenia, and the ranking of efficacy from high to low is paliperidone ER >
      aripiprazole > ziprasidone. Paliperidone ER can impair lipid metabolism
      potentially but had no influence on glucose metabolism. Aripiprazole can damage
      glucose metabolism and has little influence on lipid metabolism. Ziprasidone is
      considered an atypical antipsychotic with no evidence of harm to glucose and
      lipid metabolism.

PMID- 24446540
TI  - In memorium: Herbert Eguda Nieburgs, M.D. 1913-2013.

PMID- 24446541
TI  - Differentiating bipolar I and II disorders and the likely contribution of DSM-5
      classification to their cleavage.
AB  - Current diagnostic criteria define bipolar I (BP I) and bipolar II (BP II)
      disorders as distinct conditions, differing only slightly by clinical features.
      This review seeks to identify commonalities and differentiating features across
      the two sub-types, and emphasize that differences in causes and treatments are
      likely to be highly dependent on the diagnostic criteria used to define and
      differentiate the two conditions. We undertake a literature review of candidate
      clinical features that might be anticipated to vary or be shared across BP I and
      BP II disorders, and consider the impact of DSM definition on such applied
      findings. Studies respecting DSM-IV differentiation of BP I and BP II disorders
      have generated relatively few differences across the conditions, which may
      reflect definitional similarity or commonalities across the two conditions. As
      DSM-5 decision rules are similar to those used by DSM-IV to differentiate BP I
      and BP II disorders, we argue for application studies employing DSM-5 decisions
      to examine the differential impact of three features that weight BP I assignment
      (i.e. psychosis, hospitalization and/or impairment) and examine other sets of
      differentiating criteria.

PMID- 24446542
TI  - The use of NARX neural network for modeling of adsorption of zinc ions using
      activated almond shell as a potential biosorbent.
AB  - In this study, nonlinear autoregressive model processes with exogenous input
      (NARX) are applied for the prediction of percentage adsorption efficiency for the
      removal of zinc ions from wastewater by activated almond shell. The effect of
      operational parameters such as pH, dosage, particle size and initial metal ions
      concentration are studied to optimize the conditions for maximum removal of zinc
      ions. The model is first developed using a two layer NARX network. A comparison
      between the model results and experimental data showed that the NARX model is
      able to predict the removal of zinc ions from wastewater. The outcomes of
      suggested NARX modeling were then compared to batch experimental studies. The
      results show that activated almond shell is an efficient sorbent and NARX
      network, which is easy to implement and is able to model the batch experimental
      system.

PMID- 24446543
TI  - Amino acid discrimination by the nuclear encoded mitochondrial arginyl-tRNA
      synthetase of the larva of a bruchid beetle (Caryedes brasiliensis) from
      northwestern Costa Rica.
AB  - L-canavanine, the toxic guanidinooxy analogue of L-arginine, is the product of
      plant secondary metabolism. The need for a detoxifying mechanism for the producer
      plant is self-evident but the larvae of the bruchid beetle Caryedes brasiliensis,
      that is itself a non-producer, have specialized in feeding on the Lcanavanine
      containing seeds of Dioclea megacarpa. The evolution of a seed predator that can
      imitate the enzymatic abilities of the host permits us to address the question of
      whether the same problem of amino acid recognition in two different kingdoms has
      been solved by the same mechanism. A discriminating arginyl-tRNA synthetase,
      detected in a crude C. brasiliensis larval extract, was proposed to be
      responsible for insect's ability to survive the diet of L-canavanine (Rosenthal,
      G. A., Dahlman, D. L., and Janzen, D. H. (1976) A novel means for dealing with L
      canavanine, a toxic metabolite. Science 192, 256e258). Since the arginyl-tRNA
      synthetase of at least three genetic compartments (insect cytoplasmic, insect
      mitochondrial and insect gut microflora) may participate in conferring L
      canavanine resistance, we investigated whether the nuclear-encoded C.
      brasiliensis mitochondrial arginyl-tRNA synthetase plays a role in this
      discrimination. Steady state kinetics of the cloned, recombinant enzyme have
      revealed and quantified an amino acid discriminating potential of the
      mitochondrial enzyme that is sufficient to account for the overall L-canavanine
      misincorporation rate observed in vivo. As in the cytoplasmic enzyme of the L
      canavanine producer plant, the mitochondrial arginyl-tRNA synthetases from a
      specialist seed predator relies on a kinetic discrimination that prevents L
      canavanine misincorporation into proteins.

PMID- 24446544
TI  - Novel aquatic silk genes Simulium (Psilozia) vittatum (Zett) Diptera: Simuliidae.
AB  - The silks of arthropods have an elementary role in the natural history of the
      organisms that spin them, yet they are coded by rapidly evolving genes leading
      some authors to speculate that silk proteins are non-homologous proteins co-opted
      multiple times independently for similar functions. However, some general
      structural patterns are emerging. In this work we identified three major silk
      gland proteins using a combined biochemical, proteomic, next-generation
      sequencing and bioinformatic approach. Biochemical characterization determined
      that they were phosphorylated with multiple isoforms and potentially differential
      phosphorylation. Structural characterization showed that their structure was more
      similar to silk proteins from distantly related aquatic Trichopteran species than
      more closely related terrestrial or aquatic Diptera. Overall, our approach is
      easily transferable to any non-model species and if used across a larger number
      of aquatic species, we will be able to better understand the processes involved
      in linking the secondary structure of silk proteins with their function between
      in an organisms and its habitat.

PMID- 24446545
TI  - Reorganization of the plant cortical microtubule array.
AB  - The interphase microtubule arrays in flowering plant cells assemble at the cell
      cortex into patterns that affect cellular morphogenesis. A decade of live cell
      imaging studies has provided significant information about the in vivo properties
      of the microtubule polymers. Efforts to extrapolate individual properties to
      larger roles in organizing or patterning the microtubule array have produced
      models focused on self-organization and local levels of biological control.
      Recent studies looking at cortical microtubule arrays as they transition from an
      existing pattern to a new pattern have re-emerged as a testbed for examining
      these models and the molecular hypotheses underpinning them. The evidence
      suggests that microtubule patterning is locally controlled on the scale of a cell
      face, using or circumventing self-organizating properties as necessary.

PMID- 24446546
TI  - Understanding myosin functions in plants: are we there yet?
AB  - Myosins are motor proteins that drive movements along actin filaments and have
      long been assumed to be responsible for cytoplasmic streaming in plant cells.
      This conjecture is now firmly established by genetic analysis in the reference
      species, Arabidopsis thaliana. This work and similar approaches in the moss,
      Physcomitrella patens, also established that myosin-driven movements are
      necessary for cell growth and polarity, organelle distribution and shape, and
      actin organization and dynamics. Identification of a mechanistic link between
      intracellular movements and cell expansion has proven more challenging, not the
      least because of the high level of apparent genetic redundancy among myosin
      family members. Recent progress in the creation of functional complementation
      constructs and identification of interaction partners promises a way out of this
      dilemma.

PMID- 24446547
TI  - The actin cytoskeleton in root hairs: all is fine at the tip.
AB  - Filamentous actin forms characteristic bundles in plant cells that facilitate
      cytoplasmic streaming. In contrast, networks of actin exhibiting fast turnover
      are found especially near sites of rapid cell expansion. These networks may serve
      various functions including delivering and retaining vesicles while preventing
      penetration of organelles into the area where cell growth occurs thereby allowing
      fast turnover of vesicles to and from the plasma membrane. Root hairs elongate by
      polarized growth at their tips and the local accumulation of fine F-actin near
      the tip has provided valuable insight into the organization of these networks.
      Here we will sequentially focus on the role of the actin cytoskeleton in root
      hair tip growth and on how activities of different actin binding proteins in the
      apical part of growing root hairs contribute to build the fine F-actin
      configuration that correlates with tip growth.

PMID- 24446549
TI  - The strengths and limitations of the Ukrainian healthcare system.

PMID- 24446548
TI  - fMRI response to negative words and SSRI treatment outcome in major depressive
      disorder: a preliminary study.
AB  - Clinically useful predictors of treatment outcome in major depressive disorder
      (MDD) remain elusive. We examined associations between functional magnetic
      resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active
      negative word processing and subsequent selective serotonin reuptake inhibitor
      (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an
      emotional word processing fMRI task, and then received eight weeks of
      standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD
      responses to negative words in midbrain, dorsolateral prefrontal cortex,
      paracingulate, anterior cingulate, thalamus and caudate nuclei correlated
      significantly with greater improvement following escitalopram treatment.
      Activation of these regions in response to negative words correlated
      significantly with reaction time for rating word relevance. Maximally predictive
      clusters of voxels identified using a cross-validation approach predicted 48% of
      the variance in response to treatment. This study provides preliminary evidence
      that SSRIs may be most beneficial in patients who are less able to engage
      cognitive control networks while processing negative stimuli. Differences between
      these findings and previous fMRI studies of SSRI treatment outcome may relate to
      differences in task design. Regional BOLD responses to negative words predictive
      of SSRI outcome in this study were both overlapping and distinct from those
      predictive of outcome with cognitive behavioral therapy (CBT) in previous studies
      using the same task. Future studies may examine prediction of differential
      outcome across treatments in the context of a randomized controlled trial.

PMID- 24446550
TI  - The regional differences in the contribution of nitric oxide synthase to skin
      blood flow at forearm and lower leg sites in response to local skin warming.
AB  - We investigated the role of nitric oxide synthase (NOS) on regional cutaneous
      vascular function at rest (thermoneutral conditions) and during the vasodilator
      response to increased local skin temperature (Tloc). Dorsal forearm and lateral
      leg sites were instrumented with microdialysis fibers, local heaters, and laser
      Doppler probes. All sites were heated from 33  degrees C to 42  degrees C. Each
      limb had 1 skin site treated with l-NAME to inhibit NOS, and 1 site infused with
      lactated Ringer's to serve as a control. Basal cutaneous vascular conductance
      (CVC) was measured at 33  degrees C, forearm sites averaged 14 +/- 1%max and 17
      +/- 1%max at l-NAME and control sites, respectively (P = 0.26). CVC sites in the
      leg were different between l-NAME (17 +/- 1%max) and control (27 +/- 2%max) (P =
      0.04). CVC between the forearm and the leg across control sites differed (P <
      0.05). In contrast, at l-NAME treated sites, there was no difference between the
      forearm and leg sites (P = 0.23). When Tloc was increased to 42  degrees C, CVC
      at the control sites differed between the forearm 93 +/- 1%max and leg 98 +/-
      1%max (P = 0.02). There were no differences between the arm and leg at l-NAME
      treated sites at 42  degrees C (P = 0.45). The findings of the current study were
      that the contribution of nitric oxide (NO) to the vasodilator response to an
      elevated Tloc is consistent between the arm and the leg, and, under thermoneutral
      conditions (33  degrees C), NO plays a larger role in the basal vascular function
      in the legs than that of the forearm. Accordingly, these data suggest, in part,
      that the differences in basal CVC between the forearm and leg are due to NOS
      activity.

PMID- 24446551
TI  - The crystal structure of novel chondroitin lyase ODV-E66, a baculovirus envelope
      protein.
AB  - Chondroitin lyases have been known as pathogenic bacterial enzymes that degrade
      chondroitin. Recently, baculovirus envelope protein ODV-E66 was identified as the
      first reported viral chondroitin lyase. ODV-E66 has low sequence identity with
      bacterial lyases at <12%, and unique characteristics reflecting the life cycle of
      baculovirus. To understand ODV-E66's structural basis, the crystal structure was
      determined and it was found that the structural fold resembled that of
      polysaccharide lyase 8 proteins and that the catalytic residues were also
      conserved. This structure enabled discussion of the unique substrate specificity
      and the stability of ODV-E66 as well as the host specificity of baculovirus.

PMID- 24446552
TI  - The 2014 version of the gene table of monogenic neuromuscular disorders (nuclear
      genome).

PMID- 24446553
TI  - Mood disorders and parity - a clue to the aetiology of the postpartum trigger.
AB  - BACKGROUND: Episodes of postpartum psychosis have been associated with first
      pregnancies in women with bipolar I disorder. It is unclear, however, if the
      effect extends to episodes at other times in relation to childbirth and to women
      with other mood disorders such as major depression and bipolar II disorder. This
      primiparity effect, which is also seen in other pregnancy related conditions such
      as pre-eclampsia, is a potentially important clue to the aetiology of childbirth
      related mood episodes. METHODS: Participants were interviewed and case notes
      reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. Data on
      the occurrence of episodes in pregnancy and the postpartum were available on 3345
      full term deliveries from 1667 participants, 934 with bipolar I disorder (BD-I),
      278 with bipolar II disorder (BD-II) and 455 with recurrent major depression
      (RMD). RESULTS: Onsets of psychosis/mania within 6 weeks of childbirth were
      overrepresented in primiparae (p=0.007) with BD-I. Although primiparity was not
      associated with perinatal bipolar depression, there was an association with the
      onset of depression within 6 weeks in women with RMD (p=0.035). Whilst women
      experiencing a postpartum episode were less likely to go on to have further
      children, this did not account for the association with primiparity. LIMITATIONS:
      Data were collected retrospectively. Information on pharmacological treatment was
      not available. CONCLUSIONS: Primiparity is associated not only with postpartum
      psychosis/mania in BD-I, but also with postpartum depression in RMD. Psychosocial
      factors and biological differences between first and subsequent pregnancies may
      play a role and are candidates for examination in further studies.

PMID- 24446554
TI  - High prevalence of Borrelia burgdorferi s.l. in the European red   squirrel 
      Sciurus vulgaris in France.
AB  - The European red squirrel (Sciurus vulgaris) has long been suspected to be a
      reservoir host of the agents of Lyme borreliosis, in particular B. burgdorferi
      sensu stricto (s.s.). However, very few data support this hypothesis. Hereafter,
      we investigated the infections with B. burgdorferi genospecies in road-killed red
      squirrels collected across France. We also characterized the diversity of hard
      tick species collected from a subsample of hosts. DNA of B. burgdorferi
      genospecies were detected and identified from PCR products in ear biopsies using
      reverse line blot hybridization. Variation in prevalence was investigated accord
      ing to biogeographic areas (Mediterranean, Atlantic, Continental, and Alpine),
      season, sex, relative age, and body mass from 273 squirrels collected 2003-2010.
      Among the 746 identified tick specimens, no adult was observed, 63% were nymphs,
      and 37% were larvae all belonging to the species Ixodes ricinus except one nymph
      identified as I. trianguliceps. Overall, no squirrels of Mediterranean origin and
      no unweaned juveniles were found infested by hard ticks. Only season explained
      variation in I. ricinus abundance on squirrels, with more ticks present in spring
      to summer than in autumn to winter. Squirrels of Mediterranean origin (n = 20)
      were not found infected with B. burgdorferi sensu-lato (s.l.), which is almost
      certainly related to the low occurrence of I. ricinus in this region. Based on
      individuals analyzed in the other regions of France, 11.5% (n = 26) unweaned
      young harboured B. burgdorferi s.l., which indicates that infection occurred
      already in the nest. In adults (n = 227), the prevalence of infection with B.
      burgdorferi s.l. was 27.3%, with 18.9% B. burgdorferi s.s., 11.9% B. afzelii, and
      3.5% B. garinii. The season and the body mass, sex, and geographic origin of
      adults had no effect on the frequency of infection. Infection prevalence of S.
      vulgaris is among the highest found in rodents in Europe, particularly for B.
      burgdorferi s.s. supporting the hypothesis that sciurids are particularly
      suitable hosts for this genospecies.

PMID- 24446555
TI  - Molecular characterization of an alanine-, proline-, glycine-,  threonine-, and
      serine-rich protein of the hard tick Haemaphysalis  qinghaiensis and its effect
      as a vaccine against tick infestation in  sheep.
AB  - An immunological tick control approach has been proved to be the most promising
      alternative strategy compared to the current usage of acaricides that suffers
      from a number of serious limitations. The success of this method is mainly
      dependent on the identification of tick antigen candidates. Here, the complete
      sequence of a positive clone Hq15 that we screened from a cDNA library of
      Haemaphysalis qinghaiensis was cloned by using rapid amplification of cDNA ends.
      Hq15 contains an open reading frame (ORF) of 1851 bp that codes for 616 amino
      acid residues with a coding capacity of 61 kDa. The deduced Hq15 amino acid
      sequence was characterized by a high content of alanine (13.80%), proline
      (12.82%), glycine (12.18%), threonine (10.71%), and serine (10.06%). Sequence
      similarity and phylogenetic analyses indicated that Hq15 might encode a novel
      protein of the tick. Expression analysis by reverse transcription polymerase
      chain reaction indicated that the gene was expressed in every developmental stage
      of the tick in its salivary glands, but not in the midgut. The cDNA was expressed
      as glutathione S-transferase-fused protein in a prokaryotic system. Vaccination
      of sheep with rHq15 conferred a significant protective immunity in sheep,
      resulting in a reduction of the amount of eggs laid by each tick compared to the
      controls. These results show that rHq15 might be one of the candidate vaccine
      molecules for the control of ticks.

PMID- 24446556
TI  - Phylogenetic relationships of Francisella-like endosymbionts detected  in two
      species of Amblyomma from snakes in Thailand.
AB  - Ticks are important vectors of several bacterial pathogens, including
      Francisella. In this study, a total of 24 adult ticks (Amblyomma varanense and
      Amblyomma helvolum) collected from 4 species of snake from 3 provinces of
      Thailand was screened for the presence of Francisella-like endosymbionts (FLEs)
      by PCR. FLEs were detected in 46% (11/24) of all ticks examined. A phylogenetic
      analysis of the 16S rDNA sequence indicated that the 11 distinct genotypes of
      FLEs amplified from A. varanense and A. helvolum (from Khon Kaen and Pichit
      provinces, respectively) are in the same group, along with other FLEs amplified
      from the other tick genera. Interestingly, these FLEs are closely related to, but
      distinct (different clade) from, the FLEs isolated from different tick species
      previously reported. This work represents the first report of Francisella spp. in
      snake ticks from Thailand.

PMID- 24446557
TI  - Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy
      in rats.
AB  - Melanocortins are endogenous peptides that exert protective actions on the host
      physiology. The broad modulatory effects of these molecules suggest that they
      might influence the mediator network induced during liver regeneration. The
      research aim was to determine if melanocortin treatment alters liver molecular
      changes induced by partial hepatectomy (PH). Rats under isoflurane anesthesia
      were subjected to standard 70% PH or sham surgery. Animals received a single i.v.
      injection of Nle4, DPhe7-alpha-melanocyte stimulating hormone (NDP-MSH) or saline
      30 min before surgery. Sacrifice was performed at time intervals between 4 and 72
      h. A preliminary screening based on TaqMan low-density array (TLDA) identified 71
      transcripts altered by PH. Real-time PCR analysis revealed that NDP-MSH modulated
      the expression of a substantial proportion of these transcripts including several
      chemokines and their receptors. The critical signaling pathway interleukin-6 (IL
      6)/signal transducer and activator of transcription (STAT)/suppressor of cytokine
      signaling (SOCS) was significantly enhanced by NDP-MSH. Further, peptide
      treatment considerably reduced the decline of IkappaBalpha protein caused by PH.
      Although the final organ regeneration was not substantially affected, NDP-MSH
      modulated expression of cell cycle mediators and exerted subtle influences on
      hepatocyte replication. Most of the changes brought about by NDP-MSH, a peptide
      approved for clinical use, should be salutary during liver regeneration.

PMID- 24446559
TI  - Consultation on global influenza surveillance, Geneva,10-12 July 2013.

PMID- 24446558
TI  - Schistosomiasis: number of people receiving preventive chemotherapy in 2012.

PMID- 24446560
TI  - Monthly report on dracunculiasis cases, January-November 2013.

PMID- 24446561
TI  - Status quo of hybrid coronary revascularization for multi-vessel coronary artery
      disease.
AB  - Hybrid coronary revascularization (HCR) combines bypass grafting of the left
      anterior descending (LAD) coronary artery with percutaneous coronary intervention
      (PCI) of non-LAD vessels. HCR has been performed as an alternative to CABG or
      multi-vessel PCI in thousands of patients since the late 1990s. In this review
      article, we provide an overview on patient selection, procedural sequence and
      timing, use of surgical techniques and anti-platelet agents. Additionally,
      patient recovery, satisfaction, costs and clinical outcomes of individual studies
      after HCR are evaluated. Future directions are also discussed, including the need
      for adequately powered randomized trials.

PMID- 24446563
TI  - Behavioral and language variants of frontotemporal dementia: a review of key
      symptoms.
AB  - While recent advances in the development of neuroimaging and molecular biomarkers
      for studying neurodegenerative conditions have revolutionized the field, dementia
      remains a clinical diagnosis. No component of the diagnostic process is more
      crucial than obtaining a good history. Getting to know the first manifestations
      of the disease, tracking their evolution and functional impact, combined with a
      targeted neurological examination, further guides differential diagnosis. This
      paper summarizes the key symptoms of the behavioral and language variants of
      frontotemporal dementia. The behavioral variant of frontotemporal dementia
      (bvFTD) is characterized by severe changes in behavior and personality such as
      disinhibition, apathy, loss of empathy, or stereotypic behavior, leading to a
      loss of social competence. Executive functions are impaired, while memory and
      visuospatial skills are relatively better preserved. By contrast, the language
      variants or primary progressive aphasias (PPAs) are marked by prominent language
      disturbances that can be subclassified into a non-fluent/agrammatic variant
      (naPPA), a semantic variant (svPPA), and a logopenic variant (lvPPA). Although
      combined characterization of clinical, imaging, biological and genetic biomarkers
      is essential to establish a detailed diagnosis of such heterogeneous conditions,
      the author emphasizes the importance of accurate recognition of key symptoms that
      can lead to better identification of underlying neuropathology and appropriate
      treatment approaches.

PMID- 24446562
TI  - Cerebral blood flow autoregulation is preserved after hypothermic circulatory
      arrest.
AB  - BACKGROUND: Patients undergoing aortic operations with hypothermic circulatory
      arrest (HCA) may require prolonged rewarming, a maneuver associated with impaired
      cerebral blood flow (CBF) autoregulation. The purpose of this study was to
      determine the effects of HCA on CBF autoregulation with a validated method based
      on near-infrared spectroscopy. METHODS: Regional cerebral oxygen saturation
      (rSco2) was monitored in 25 patients undergoing aortic reconstructive operations.
      HCA was used in 13 patients. Autoregulation was measured continuously during the
      operation by calculating the linear correlation coefficient between low-frequency
      changes in rSco2 and mean arterial pressure (MAP), generating the variable
      cerebral oximetry index (COx). When CBF autoregulation is functional, COx is near
      0, because CBF and MAP are not correlated, but approaches 1 when autoregulation
      is impaired (ie, CBF is pressure passive). On the basis of prior studies,
      impaired autoregulation was defined as COx exceeding 0.3. RESULTS: COx did not
      differ between HCA and non-HCA groups before cardiopulmonary bypass or during the
      cooling phase of the operation, although the lower limit of autoregulation tended
      to be lower in patients before HCA (p = 0.053). During patient rewarming, COx was
      lower in the HCA group (p = 0.045), and abnormal COx was less frequent (31% vs
      75%, p = 0.047) compared with the non-HCA group. CONCLUSIONS: During aortic
      reconstructive operations, CBF autoregulation is preserved during the cooling
      phase of the procedure in patients undergoing HCA. Perfusion maneuvers associated
      with HCA may be protective against impaired autoregulation during rewarming
      compared with the non-HCA group.

PMID- 24446564
TI  - Age-related increases in human lymphocyte DNA damage: is there a role of aerobic
      fitness?
AB  - Oxidative stress has been advanced as one of the major causes of damage to DNA
      and other macromolecules. Although physical exercise may also increase oxidative
      stress, an important role has been recognized for regular exercise in improving
      the overall functionality of the body, as indicated by an increase in maximal
      aerobic uptake ((V)O2max), and in resistance to cell damage. The aims of this
      study were 1) to evaluate the association between DNA damage in human lymphocytes
      and age and 2) to evaluate the association between DNA damage in human
      lymphocytes and ((V)O2max. The sample was composed of 36 healthy and nonsmoking
      males, aged from 20 to 84 years. ((V)O2max was evaluated through the Bruce
      protocol with direct measurement of oxygen consumption. The comet assay was used
      to evaluate the DNA damage, strand breaks and formamidopyrimidine DNA glycosylase
      (FPG)-sensitive sites. We found a positive correlation of age with DNA strand
      breaks but not with FPG-sensitive sites. ((V)O2max was significantly inversely
      related with DNA strand breaks, but this relation disappeared when adjusted for
      age. A significantly positive relation between ((V)O2max and FPG-sensitive sites
      was verified. In conclusion, our results showed that younger subjects have lower
      DNA strand breaks and higher (V)O2max compared with older subjects and FPG
      sensitive sites are positively related with ((V)O2max, probably as transient
      damage due to the acute effects of daily physical activity.

PMID- 24446565
TI  - The evolution of landscape genetics.
AB  - The main objective of this special section is not to review the broad field of
      landscape genetics, but to provide a glimpse of how the developing landscape
      genetics perspective has the potential to change the way we study evolution.
      Evolutionary landscape genetics is the study of how migration and population
      structure affects evolutionary processes. As a field it dates back to Sewall
      Wright and the origin of theoretical population genetics, but empirical tests of
      adaptive processes of evolution in natural landscapes have been rare. Now, with
      recent developments in technology, methodology, and modeling tools, we are poised
      to trace adaptive genetic variation across space and through time. Not only will
      we see more empirical tests of classical theory, we can expect to see new
      phenomena emerging, as we reveal complex interactions among evolutionary
      processes as they unfold in natural landscapes.

PMID- 24446566
TI  - Winter wisdom.

PMID- 24446567
TI  - In good company.

PMID- 24446568
TI  - Shop, eat, love.

PMID- 24446569
TI  - Eating expertise.

PMID- 24446570
TI  - Proceedings of the 56th International Meeting of Clinical Endocrinology, June 6
      7, 2013, Paris, France.

PMID- 24446571
TI  - Limb transplantation: from a concept to reality over the last 50 years.

PMID- 24446573
TI  - Toward a child-centered approach to evaluating claims of alienation in high
      conflict custody disputes.
AB  - Theories of parental alienation abound in high-conflict custody cases. The image
      of one parent brainwashing a child against the other parent fits with what we
      think we know about family dynamics during divorce. The concept of a diagnosable
      "Parental Alienation Syndrome" ("PAS") developed as an attempt to explain this
      phenomenon, but it has been widely discredited by mental health professionals and
      thus fails the standard for evidentiary admissibility. Nevertheless, PAS and
      related theories continue to influence the decisions of family courts, and even
      in jurisdictions that explicitly reject such theories, judges still face the
      daunting task of resolving these volatile cases. In the midst of this highly
      adversarial process, children deserve independent representation to ensure that
      their interests remain front and center. Mandating the appointment of guardians
      ad litem in cases involving allegations of abuse or alienation will assist courts
      in conducting individualized, fact-specific investigations into such allegations
      to craft custody orders that serve the best interests of children.

PMID- 24446572
TI  - Comparative effectiveness research as choice architecture: the behavioral law and
      economics solution to the health care cost crisis.
AB  - With the Patient Protection and Affordable Care Act ("ACA") set to dramatically
      increase access to medical care, the problem of rising costs will move center
      stage in health law and policy discussions. "Consumer directed health care"
      proposals, which provide patients with financial incentives to equate marginal
      costs and benefits of care at the point of treatment, demand more decisionmaking
      ability from consumers than is plausible due to bounded rationality. Proposals
      that seek to change the incentives of health care providers threaten to create
      conflicts of interest between doctors and patients. New approaches are
      desperately needed. This Article proposes a government-facilitated but market
      based approach to improving efficiency in the private market for medical care
      that I call "relative value health insurance." This approach focuses on the
      "choice architecture" necessary to enable even boundedly rational patients to
      contract for an efficient level of health care services through their health
      insurance purchase decisions. It uses comparative effectiveness research, which
      the ACA funds at a significant level for the first time, to rate medical
      treatments on a scale of one to ten based on their relative value, taking into
      account expected costs and benefits. These relative value ratings would enable
      consumers to contract with insurers for different levels of medical care at
      different prices, reflecting different cost-quality trade-offs. The Article
      describes both the benefits of relative value health insurance and the
      impediments to its implementation. It concludes with a brief discussion of how
      relative value ratings could also help to rationalize expenditures on public
      health insurance programs.

PMID- 24446574
TI  - The silver tsunami: states have a fairly long to-do list to get ready for the
      health care needs of an aging America.

PMID- 24446575
TI  - A wealth of public health: there's renewed effort to integrate the many public
      health programs into the overall health system.

PMID- 24446576
TI  - Preventable deaths on the rise: growing numbers of overdoses, suicides, and brain
      injuries have lawmakers searching for solutions.

PMID- 24446577
TI  - The value of Medicaid to older households.

PMID- 24446578
TI  - Do financial incentives induce disability insurance recipients to return to work?

PMID- 24446579
TI  - In reply.

PMID- 24446581
TI  - Narcissistic grandiosity and narcissistic vulnerability in psychotherapy.
AB  - This article briefly summarizes the empirical and clinical literature underlying
      a contemporary clinical model of pathological narcissism. Unlike the DSM
      Narcissistic Personality Disorder (NPD), this clinical model identifies and
      differentiates between two phenotypic themes of dysfunction-narcissistic
      grandiosity and narcissistic vulnerability-that can be expressed both overtly and
      covertly in patients' ways of thinking, feeling, behaving, and participating in
      treatment. Clinical recognition that narcissistic patients can and often do
      present for psychotherapy in vulnerable states of depression, anxiety, shame, and
      even suicidality increases the likelihood of accurate diagnosis and effective
      treatment planning. This article provides case examples derived from
      psychotherapies with narcissistic patients to demonstrate how narcissistic
      grandiosity and narcissistic vulnerability concurrently present in patients who
      seek treatment.

PMID- 24446580
TI  - Antibody-free detection of Mycobacterium tuberculosis antigen using customized
      nanotraps.
AB  - Rapid screening and diagnosis of tuberculosis disease (TB) is still challenging
      and critically needed for global TB control efforts. In this study, we present a
      rapid and streamlined technology, using precisely engineered silica nanopore thin
      films, which are optimized for pore size, structure, capillary force, and film
      thickness, to isolate Mycobacterium tuberculosis (MTB) antigens in laboratory and
      clinical samples for rapid TB screening. This technology, referred to here as on
      chip fractionation, is integrated with high-throughput matrix-assisted laser
      desorption/ionization time-of flight mass spectrometry to screen and identify
      fragments of the MTB antigen, CFP-10, from complex biological samples, without
      use of immunoaffinity agents. With the use of this comprehensive approach, we
      were able to clearly distinguish a clinical isolate of MTB from a nonTB species
      of the genus Mycobacterium avium grown in liquid culture media. This assay can
      reach a detection limit of 10 fmol and an isolation rate of 90% for the antigen
      CFP-10. Our strategy has significant potential to fill the conceptual and
      technical gaps in rapid diagnosis of active TB disease. 

PMID- 24446582
TI  - Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of
      allergic asthma.
AB  - OBJECTIVE: Interleukin (IL)-33 is involved in the development of lung
      inflammation by inducing or amplifying Th2 type-mediated responses in various
      animal models of allergic asthma. The ST2 gene is a member of the IL-1 receptor
      family, producing a transmembrane form (ST2L) and a soluble secreted form (sST2).
      sST2 has been shown to block this IL-33/ST2 signaling pathway. This study aimed
      to investigate whether anti-IL-33 and sST2 reduced airway inflammation in a
      murine model of asthma. METHODS: BALB/c mice were sensitized and challenged with
      ovalbumin (OVA), and the effect of sST2 and anti-IL-33 antibody on airway
      inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we
      measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid
      when treated with sST2 or anti-IL-33. RESULTS: We observed that anti-IL-33
      antibody and sST2 exert a negative regulation on OVA-mediated allergic airway
      inflammation. Both treatments reduced total cell counts and eosinophil counts in
      BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5, and IL
      13 in BAL fluid were also significantly decreased after both treatments. However,
      there were no changes in the level of TGF- beta1 and IL-10 after each treatment.
      CONCLUSIONS: These results suggest that anti-IL-33 as well as sST2 have
      therapeutic potential for allergic asthma through inhibition of Th2 cytokine
      production.

PMID- 24446583
TI  - Profiling oil sands mixtures from industrial developments and natural
      groundwaters for source identification.
AB  - The objective of this study was to identify chemical components that could
      distinguish chemical mixtures in oil sands process-affected water (OSPW) that had
      potentially migrated to groundwater in the oil sands development area of northern
      Alberta, Canada. In the first part of the study, OSPW samples from two different
      tailings ponds and a broad range of natural groundwater samples were assessed
      with historically employed techniques as Level-1 analyses, including
      geochemistry, total concentrations of naphthenic acids (NAs) and synchronous
      fluorescence spectroscopy (SFS). While these analyses did not allow for reliable
      source differentiation, they did identify samples containing significant
      concentrations of oil sands acid-extractable organics (AEOs). In applying Level-2
      profiling analyses using electrospray ionization high resolution mass
      spectrometry (ESI-HRMS) and comprehensive multidimensional gas chromatography
      time-of-flight mass spectrometry (GC * GC-TOF/MS) to samples containing
      appreciable AEO concentrations, differentiation of natural from OSPW sources was
      apparent through measurements of O2:O4 ion class ratios (ESI-HRMS) and diagnostic
      ions for two families of suspected monoaromatic acids (GC * GC-TOF/MS). The
      resemblance between the AEO profiles from OSPW and from 6 groundwater samples
      adjacent to two tailings ponds implies a common source, supporting the use of
      these complimentary analyses for source identification. These samples included
      two of upward flowing groundwater collected <1 m beneath the Athabasca River,
      suggesting OSPW-affected groundwater is reaching the river system. 

PMID- 24446585
TI  - Determination of energy level alignment and coupling strength in 4,4'-bipyridine
      single-molecule junctions.
AB  - We measure conductance and thermopower of single Au-4,4'-bipyridine-Au junctions
      in distinct low and high conductance binding geometries accessed by modulating
      the electrode separation. We use these data to determine the electronic energy
      level alignment and coupling strength for these junctions, which are known to
      conduct through the lowest unoccupied molecular orbital (LUMO). Contrary to
      intuition, we find that, in the high-conductance junction, the LUMO resonance
      energy is further away from the Au Fermi energy than in the low-conductance
      junction. However, the LUMO of the high-conducting junction is better coupled to
      the electrode. These results are in good quantitative agreement with self-energy
      corrected zero-bias density functional theory calculations. Our calculations show
      further that measurements of conductance and thermopower in amine-terminated
      oligophenyl-Au junctions, where conduction occurs through the highest occupied
      molecular orbitals, cannot be used to extract electronic parameters as their
      transmission functions do not follow a simple Lorentzian form. 

PMID- 24446588
TI  - Photoresponsive smectic liquid crystalline multipods and hyperbranched azo
      polymers.
AB  - Liquid crystalline azobenzene containing triped and tetraped monomers were
      designed and synthesized and further used as B3 and B4 type monomers to form
      hyperbranched polymers with tetraethylene glycol as the A2 type comonomer. The
      mesophase characteristics of the multiarm-star mesogens and hyperbranched
      polymers were analyzed using various instrumentation techniques like differential
      scanning calorimetry (DSC), polarized light microscopy (PLM) and variable
      temperature XRD. The multipod monomers as well as hyperbranched polymers
      exhibited thermotropic smectic liquid crystalline characteristics with a tendency
      toward higher ordered smectic LC phases with increased branching. The
      hyperbranched polymers exhibited lamellar organization even in the as-solvent
      precipitated powder sample indicating higher extent of nanosegregation. Their
      potential application as fast switching photochromic materials was highlighted by
      carrying out isothermal photoswitching experiments in the LC state. Reversible
      isothermal smectic-isotropic phase transition could be achieved by UV irradiation
      in <1 s in the multipod monomers, while it required >2 s UV irradiation in the
      case of the hyperbranched polymers. 

PMID- 24446586
TI  - Systemic myositis due to Campylobacter infection.

PMID- 24446589
TI  - New universal strain software accurately assesses cardiac systolic and diastolic
      function using speckle tracking echocardiography.
AB  - BACKGROUND: We have developed new universal strain software (USS) that can be
      used to perform speckle tracking of any Digital Imaging and Communications in
      Medicine (DICOM) image, regardless of the ultrasound system used to obtain it.
      METHODS: Fifty patients prospectively underwent echocardiography immediately
      prior to cardiac catheterization. Biplane peak global longitudinal strain (GLS),
      peak systolic longitudinal strain rate (SSR), peak early diastolic longitudinal
      strain rate (DSR), and peak early diastolic circumferential strain rate (DCSR)
      were determined using conventional strain software (CSS) that uses raw data, and
      using the new USS applied to DICOM images. RESULTS: Universal strain software
      correlated with CSS for GLS (r = 0.78, P < 0.001), SSR (r = 0.78, P < 0.001), DSR
      (r = 0.54, P < 0.001), and DCSR (r = 0.43, P = 0.019). GLS and SSR using USS
      correlated with left ventricular ejection fraction (LVEF) (r = -0.67 and -0.71,
      respectively) as well as using CSS (r = -0.66 and -0.71). Patients with diastolic
      dysfunction had significantly lower DSR (0.61 vs. 0.87/sec, P = 0.02) and DCSR
      (0.89 vs. 1.23/sec, P = 0.03), and less negative GLS (-10.8 vs. -16.1%, P =
      0.002) using USS in all patients, as well as among those with LVEF >= 50%.
      Receiver-operating characteristic (ROC) analysis for detection of diastolic
      dysfunction revealed a sensitivity and specificity of 82% and 83% for DCSR <
      1.09/sec (area under the curve [AUC = 0.80]) and 85% and 83% for GLS > -13.7%
      (AUC = 0.84) using USS. CONCLUSION: Universal strain software can be used to
      accurately assess LV systolic and diastolic function using speckle tracking
      echocardiography.

PMID- 24446590
TI  - A double-blind randomised clinical trial of two techniques for gingival
      displacement.
AB  - Knowledge about security and the potential damage originated by the gingival
      displacement techniques has not been described through randomised clinical
      studies. This crossover, double-blind, randomised clinical trial evaluated
      clinical and immunological factors related to conventional and cordless gingival
      displacement (GD) techniques, and patients' perceptions in 12 subjects with the
      employment of 2 GD techniques: conventional (gingival cord + 25% AlCl3 astringent
      gel) and cordless (15% AlCl3 astringent-based paste). In each subject, two
      anterior teeth were treated and a 10-day wash-out period separated the two
      treatments. Periodontal indices were evaluated before (baseline) and 1 and 10
      days after GD. Interleukin 1beta, interleukin 6 and tumour necrosis factor alpha
      concentrations in gingival crevicular fluid were measured before and 1 day after
      GD. Subjective parameters (pain, unpleasant taste and stress) were also
      evaluated. Data were analysed by one-way repeated-measures analysis of variance
      and Tukey's test (immunological factors), the Friedman test (periodontal
      parameters) and Fisher's exact or chi-squared test (subjective parameters), with
      a significance level of 95%. Gingival bleeding index, probing depth and plaque
      index values did not differ significantly between groups at any timepoint.
      Neither technique resulted in worse periodontal indices. Both techniques yielded
      similar results for pain and unpleasant taste, but conventional GD was
      significantly more stressful than cordless GD for volunteers. Both treatments
      significantly increased mean concentrations of the three cytokines, with the
      conventional technique producing the highest cytokine levels. Cordless GD is less
      stressful for patients and results in lower post-treatment levels of inflammatory
      cytokines compared with conventional GD. 

PMID- 24446591
TI  - Presence of cytomegalovirus DNA in leucocytes is associated with increased
      oxidative stress and subclinical atherosclerosis in healthy adults.
AB  - OBJECTIVE: Investigate the latent cytomegalovirus (CMV) infection as a biomarker
      of oxidative stress and atherosclerosis. METHODS: Latent CMV infection was
      diagnosed in healthy individuals with PCR-evidence of CMV DNA in peripheral
      leucocytes. Oxidative stress and atherosclerosis were measured by mitochondrial
      DNA oxidative damage index (mtDNA(DeltaCT)) and intima media thickness (IMT).
      RESULTS: The CMV DNA positive subjects had a higher mean mtDNA(DeltaCT) and
      greater IMT than subjects in the control group. CONCLUSIONS: Presence of CMV DNA
      in leucocytes, as a marker of latent CMV infection, was associated with increased
      levels of oxidative stress and subclinical atherosclerosis in healthy adults.

PMID- 24446592
TI  - When will the message begin to hit home?

PMID- 24446593
TI  - BME representation at senior nurse level is getting worse, says ex-chief.

PMID- 24446594
TI  - RCN works with trust on discrimination.

PMID- 24446595
TI  - Cut-out boosted fruit sales by 20 per cent.

PMID- 24446596
TI  - Lancet commission to tackle the poor perception of UK nursing.

PMID- 24446597
TI  - Knighted nurse is removed from the nursing register.

PMID- 24446598
TI  - One third of staff feel bullied at largest NHS organisation.

PMID- 24446599
TI  - Call to increase staff engagement as a way of improving satisfaction and care.

PMID- 24446600
TI  - Supporting role to self-manage gout.

PMID- 24446601
TI  - Respiratory conditions seen as health care's 'poor relation'.

PMID- 24446603
TI  - Nursing staff could play a major part in detecting heart disorders.

PMID- 24446604
TI  - Care pathway must meet needs of diverse communities.

PMID- 24446607
TI  - Rise in student numbers could fail to plug the retirement gap.

PMID- 24446608
TI  - School nurse retirement is being underestimated, unions warn.

PMID- 24446609
TI  - Disciplinary risk for smoking in uniform.

PMID- 24446610
TI  - Sorry need not be the hardest word for healthcare staff to say.

PMID- 24446611
TI  - Nurses of my generation must admit to misdeeds.

PMID- 24446617
TI  - Lung cancer.

PMID- 24446618
TI  - Not special enough?
AB  - The rejection of the Francis report's call for specialist registered status for
      older people's nursing disappointed many, who say it was a missed opportunity to
      declare that older people, and the nurses who care for them, are valued. Others
      believe that the government was correct to focus on all nurses, not just
      specialists.

PMID- 24446619
TI  - Understanding CHARGE.
AB  - Children and young people with rare genetic condition CHARGE can have complex and
      serious problems that nurses may know little about. A new guidance pack produced
      by the charity Sense includes valuable information that will help nurses,
      particularly health visitors, support these families.

PMID- 24446632
TI  - A home from home for older people - even if it is in the Far East.

PMID- 24446633
TI  - Nurses are being undervalued and our good name tarnished.

PMID- 24446634
TI  - As champions of good care, it is our duty to defend the NHS.

PMID- 24446635
TI  - Morbid obesity is exploited for pleasure of armchair voyeurs.

PMID- 24446637
TI  - Our most intimate data must be allowed to remain confidential.

PMID- 24446641
TI  - Meeting the psychological care needs of patients with cancer.
AB  - This article aims to explore the psychological aspects of cancer care from the
      time of diagnosis to treatment cessation. It reviews some of the main
      psychological issues associated with cancer, such as depression, anxiety, fear of
      recurrence and lack of hope, as well as identifying interventions that aim to
      improve the mental health of patients with cancer. The article discusses the
      advantages of providing such support, as well as the importance of managing a
      patient's expectations and hope trajectories. Finally, the limitations of
      providing psychological support and the implications for nursing practice are
      considered. 

PMID- 24446642
TI  - Prescribing in prison: complexities and considerations.
AB  - Prescribing in prison is challenging because of environmental constraints, drug
      seeking behaviour and the potential for drug trafficking. Risk management is,
      therefore, a fundamental part of the non-medical prescriber's role as he or she
      attempts to balance health needs with security requirements. This article
      highlights the need for an insightful, yet impartial, approach to prescribing for
      offenders. 

PMID- 24446643
TI  - Deep vein thrombosis: diagnosis and treatment.
AB  - This article aims to give nurses an insight into proximal deep vein thrombosis
      (DVT). DVT is relatively common and is associated with significant morbidity and
      mortality. Complications such as post-thrombotic syndrome, venous leg ulcers,
      recurrent venous thromboembolism (VTE) - pulmonary embolism (PE) or DVT - and
      pulmonary hypertension can develop following DVT diagnosis. There is also a risk
      that a large PE could prove fatal. While VTE prevention is a clinical priority,
      nurses should also have appropriate skills and knowledge to care for patients
      with suspected DVT. Nurses need to be aware of the signs and symptoms of DVT,
      common diagnostic tests, pharmacological and mechanical treatments, and the
      follow-up investigations patients should be offered. 

PMID- 24446644
TI  - Late-stage dementia.

PMID- 24446645
TI  - Present and correct.

PMID- 24446649
TI  - Never be too busy to care.

PMID- 24446647
TI  - Ticket to a learning opportunity.

PMID- 24446650
TI  - What caring is all about.

PMID- 24446651
TI  - Intraoperative ultrasonography with a surgeon-manipulated microtransducer during
      robotic radical prostatectomy.
AB  - Intraoperative transrectal ultrasonography during laparoscopic radical
      prostatectomy has been reported to lead to a reduction in surgical margin rates.
      However, the use of a surgeon-controlled ultrasound probe that allows for precise
      manipulation and direct interpretation of the image by a console surgeon has yet
      to be studied. The aim of the present study was to show initial feasibility using
      the microtransducer with 9-mm scan length controlled by the console surgeon
      during robot-assisted radical prostatectomy in 10 patients. The transducer is
      designed as a drop-in probe with a flexible cord for insertion through a
      laparoscopic port, and is controlled by a robotic arm with the ultrasonographic
      image shown as a console Tile-pro display. Intraoperative localization of the
      biopsy-proven cancerous hypoechoic lesion was feasible in four out of four cases.
      The microtransducer facilitated identification of the bladder neck as well as the
      appropriate level of neurovascular bundle release. Negative surgical margin was
      achieved in all 10 cases (100%), even though five of 10 patients (50%) had
      extraprostatic (pT3) disease. Recovery of erectile function and continence was
      encouraging. In conclusion, intraoperative ultrasound navigation using a drop
      type microtransducer is a novel technique that could enhance the incremental
      value of the standard information. 

PMID- 24446652
TI  - Euract: European Academy of Teachers in General Practice 22nd International
      Euract Bled Course Bled, Slovenia: 24-28 September 2013.

PMID- 24446654
TI  - Impact of sex on insulin secretion in cystic fibrosis.
AB  - CONTEXT: Cystic fibrosis-related diabetes is primarily due to a defect in insulin
      secretion. Women with cystic fibrosis (CF) are at higher risk of developing CF
      related diabetes. OBJECTIVE: The objective of the study was to examine sex
      differences in insulin and glucose homeostasis. We hypothesized that in CF, women
      would display lower insulin secretion than men. DESIGN: This was a study based on
      an ongoing observational CF cohort with a mean follow-up of 19.9 +/- 5.2 months.
      SETTING: The study was conducted at the CF clinic of the Centre Hospitalier de
      l'Universite de Montreal (Quebec, Canada). PATIENTS: From 230 adults with CF (123
      men, 107 women) of similar age and functional pulmonary status, 104 retested
      after the follow-up. Age-matched healthy individuals (25 men, 19 women) were
      included in the study. INTERVENTIONS: Participants underwent a 2-hour oral
      glucose tolerance test with 30-minute interval sample measurements. MAIN OUTCOME
      MEASURE: Plasma insulin and glucose levels were measured. RESULTS: Women with CF
      had higher overall insulin secretion as compared with men with CF (P <= .05) but
      similar to healthy women (P = .606). Men with CF had lower overall insulin
      secretion than healthy men (P = .020) and higher insulin sensitivity (P = .009)
      than women with CF. PATIENTS with CF displayed higher overall glucose excursions
      than healthy patients. Sex-related differences were still observed in the CF
      cohort after follow-up. CONCLUSIONS: Surprisingly, in CF, adult women presented
      higher insulin secretion than adult men at a comparable level with what is
      observed in healthy individuals. Potential implications of this sex dimorphism in
      CF remain to be established.

PMID- 24446655
TI  - C-type natriuretic peptide in complicated pregnancy: increased secretion precedes
      adverse events.
AB  - CONTEXT: C-type natriuretic peptide (CNP), a vasoactive product of the
      endothelium, is markedly increased during placentation in ovine pregnancy and is
      further stimulated by nutrient restriction. Whether CNP products change in human
      pregnancy is unknown. OBJECTIVES: The objective of the study was to compare
      serial changes in maternal plasma CNP peptides during normal pregnancy with
      changes in pregnancy complicated by adverse events and relate these to fetal
      growth and placental CNP content. DESIGN: This was a prospective observational
      study undertaken in a tertiary care center. METHODS: We studied changes in
      maternal plasma aminoterminal proCNP (NTproCNP) and CNP at monthly intervals,
      fetal growth, and placental and umbilical plasma CNP peptides in 51 women, 28 of
      whom experienced an adverse event and 23 were uneventful. Age matched healthy
      nonpregnant women served as a reference range for NTproCNP. RESULTS: Compared
      with nonpregnant women, maternal plasma NTproCNP in an uneventful pregnancy was
      significantly reduced from first sampling (16 wk gestation) until 36 weeks. In
      contrast, in complicated pregnancy, levels did not decline and were significantly
      higher (P < .001 by ANOVA) than in normal pregnancy from 20 weeks. Highest values
      occurred in women later developing hypertension and fetal growth disorders.
      Placental concentration of NTproCNP was unrelated to maternal NTproCNP but
      strongly correlated with cord plasma levels. CONCLUSIONS: Maternal NTproCNP is
      significantly raised in women who later exhibit a range of obstetric adverse
      events. Lack of association with placental concentrations suggests that these
      changes represent an adaptive response within the maternal circulation to a
      threatened nutrient supply to the fetus.

PMID- 24446656
TI  - A functional amino acid substitution in the glucose-dependent insulinotropic
      polypeptide receptor (GIPR) gene is associated with lower bone mineral density
      and increased fracture risk.
AB  - CONTEXT: Food ingestion decreases bone resorption, and glucose-dependent
      insulinotropic polypeptide (GIP) may mediate this effect. Mice overexpressing GIP
      have increased osteoblast activity and are rescued from age-related bone loss,
      whereas GIPR knockout mice have decreased cortical bone mass and compromised bone
      quality. Carriers of the functional variant GIPR Glu354Gln (rs1800437) have
      higher plasma glucose 2 hours after glucose ingestion, suggesting that the
      variant encoding GIPR 354Gln decreases the effect of GIP. OBJECTIVE: The
      objective of the study was to investigate the effect of GIPR Glu354Gln on bone
      mineral density (BMD) and fracture risk. DESIGN: This was a prospective,
      comprehensive, cohort study (number NCT00252408). PARTICIPANTS: A total of 1686
      perimenopausal women were included. MAIN OUTCOME MEASURES: Dual-energy X-ray
      absorptiometry was performed at baseline and after 10 years. Incident fractures
      were recorded during the follow-up and were obtained from the Danish National
      Patient Registry, giving a total follow-up time of a minimum 16 years. RESULTS:
      After 10 years, women with the minor frequency C allele of rs1800437 (354Gln) had
      significantly lower BMD at the femoral neck compared with carriers of the major G
      allele (CC: 0.755 +/- 0.015 g/cm(2) vs CG: 747 +/- 0.005 g/cm(2); GG: 0.766 +/-
      0.004 g/cm(2), P < .001). Correspondingly, total hip BMD was significantly lower
      among C allele carriers (CC: 0.881 +/- 0.016 g/cm(2); CG: 0.884 +/- 0.005
      g/cm(2); and GG: 0.906 +/- 0.004 g/cm(2), P < .001). Finally, women homozygous
      for the variant C allele had an increased risk (hazard ratio 1.6, confidence
      interval 1.0-2.6, P < .05) of nonvertebral fractures. CONCLUSION: This study
      demonstrates an association between a functional GIPR polymorphism Glu354Gln
      (rs1800437) and BMD and fracture risk. These findings further establish GIP to be
      involved in the regulation of bone density.

PMID- 24446653
TI  - European Society for Paediatric Endocrinology consensus guidelines on screening,
      diagnosis, and management of congenital hypothyroidism.
AB  - OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and
      management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature
      search was conducted to identify key articles relating to the screening,
      diagnosis, and management of CH. The evidence-based guidelines were developed
      with the Grading of Recommendations, Assessment, Development and Evaluation
      (GRADE) system, describing both the strength of recommendations and the quality
      of evidence. In the absence of sufficient evidence, conclusions were based on
      expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the
      European Society for Paediatric Endocrinology and five other major scientific
      societies in the field of pediatric endocrinology were allocated to working
      groups with assigned topics and specific questions. Each group searched the
      literature, evaluated the evidence, and developed a draft document. These papers
      were debated and finalized by each group before presentation to the full assembly
      for further discussion and agreement. RECOMMENDATIONS: The recommendations
      include: worldwide neonatal screening, approaches to assess the cause (including
      genotyping) and the severity of the disorder, the immediate initiation of
      appropriate L-T4 supplementation and frequent monitoring to ensure dose
      adjustments to keep thyroid hormone levels in the target ranges, a trial of
      treatment in patients suspected of transient CH, regular assessments of
      developmental and neurosensory functions, consulting health professionals as
      appropriate, and education about CH. The harmonization of diagnosis, management,
      and routine health surveillance would not only optimize patient outcomes, but
      should also facilitate epidemiological studies of the disorder. Individuals with
      CH require monitoring throughout their lives, particularly during early childhood
      and pregnancy.

PMID- 24446658
TI  - Oxytocin, a new determinant of bone mineral density in post-menopausal women:
      analysis of the OPUS cohort.
AB  - INTRODUCTION: Oxytocin (OT), a neurohypophysial hormone regulated by estrogen and
      leptin, may play a role in bone metabolism in humans as suggested by animal
      studies. This study assessed the relationship between OT and bone status in a
      large population of postmenopausal women. SUBJECTS AND METHODS: Subjects were
      included in the Osteoporosis and Ultrasound study, a 6-year prospective study in
      a population-based cohort. Final visit data were used for this cross-sectional
      study. OT, leptin, and estradiol serum levels were measured in 1097
      postmenopausal women and compared with bone mineral density (BMD), fractures, and
      the bone turnover markers (BTMs) procollagen type 1 N-terminal propeptide, bone
      alkaline phosphatase, and C-telopeptide of type 1 collagen. RESULTS: The median
      age was 70.8 years, 16% were osteoporotic, 48% were osteopenic, and 29% had at
      least one fracture. The OT serum level was related to spine (r = +0.12, P =
      .0002) and total hip BMD (r = +0.21, P < .0001) and with BTM (procollagen type 1
      N-terminal propeptide: r = -0.13, P < .0001, bone alkaline phosphatase: r = 
      0.07, P = .02, C-telopeptide of type 1 collagen: r = -0.18, P < .0001). The
      relationship of OT with BMD was independent of BTM. After adjustment for
      confounding factors, the correlation between OT serum level and BMD remains
      significant at the hip in women with unmeasurable estradiol or leptin above the
      median value. There was no significant relationship between OT serum levels and
      fractures. CONCLUSION: High OT levels are associated with high BMD, especially at
      the hip in women with low estradiol or high leptin serum levels. The mechanism
      may be explained by the effect of OT on bone turnover.

PMID- 24446657
TI  - Regulation of IL-1 receptor antagonist by TSH in fibrocytes and orbital
      fibroblasts.
AB  - CONTEXT: The IL-1 family plays important roles in normal physiology and mediates
      inflammation. The actions of IL-1 are modulated by multiple IL-1 receptor
      antagonists (IL-1RA), including intracellular and secreted forms. IL-1 has been
      implicated in autoimmunity, such as that occurring in Graves' disease (GD) and
      its inflammatory orbital manifestation, thyroid-associated ophthalmopathy (TAO).
      We have previously reported that CD34(+) fibrocytes, monocyte-lineage bone marrow
      derived cells, express functional TSH receptor, the central antigen in GD. When
      activated by TSH, they produce IL-6, IL-8, and TNF-alpha. Moreover, they
      infiltrate the orbit in TAO in which they transition into CD34(+) fibroblasts and
      comprise a population of orbital fibroblasts (OFs). Little is known currently
      about any relationship between TSH, TSH receptor, and the IL-1 pathway.
      OBJECTIVE: The objective of the study was to determine whether TSH regulates IL
      1RA in fibrocytes and OFs. DESIGN/SETTING/PARTICIPANTS: Fibrocytes and OFs were
      collected and analyzed from healthy individuals and those with GD in an academic
      clinical practice. MAIN OUTCOME MEASURES: Real-time PCR, Western blot analysis,
      reporter gene assays, and cell transfections were performed. RESULTS: TSH induces
      the expression of IL-1RA in fibrocytes and GD-OFs. The patterns of induction
      diverge quantitatively and qualitatively in the two cell types. This results from
      relatively small effects on gene transcription-related events but a greater
      influence on secreted IL-1RA and intracellular IL-1RA mRNA stabilities. These
      actions of TSH are dependent on the intermediate induction of IL-1alpha and IL
      1beta. CONCLUSIONS: Our findings for the first time directly link activities of
      the TSH and IL-1 pathways. Furthermore, they identify novel molecular
      interactions that could be targeted as therapy for TAO.

PMID- 24446659
TI  - Inverse correlation between circulating levels of TNF-related apoptosis-inducing
      ligand and 17beta-estradiol.
AB  - CONTEXT: The regulation of the circulating levels of TNF-related apoptosis
      inducing ligand (TRAIL), a cytokine of the TNF family, playing a key role in the
      immune surveillance against cancer, is incompletely understood. OBJECTIVE: The
      objective of the study was to investigate the potential link between TRAIL and
      17beta-estradiol. DESIGN, SETTING, AND PARTICIPANTS: Circulating TRAIL levels
      were measured by an ELISA in plasma samples (n = 246) of healthy, age-matched
      (range 30-70 y) men and women and in the sera (n = 180) of females belonging to
      different physiopathological conditions (childhood, pregnancy, under gonadotropin
      treatment, menopause) characterized by different levels of circulating 17beta
      estradiol. RESULTS: TRAIL plasma levels in women with aged younger than 50 years
      were significantly lower compared with age-matched men, whereas in woman 50 years
      old or older, TRAIL levels were significantly higher compared with the age
      matched men and with the younger women. Moreover, an analysis of women with
      different conditions revealed a significant inverse correlation between the serum
      levels of TRAIL and 17beta-estradiol, with the lowest levels of TRAIL being
      observed during pregnancy and the highest in childhood and in postmenopausal
      women. Moreover, gonadotropin treatment in women undergoing assisted reproduction
      was accompanied by an acute decrease of serum TRAIL levels. Finally, in vitro
      treatment with 17beta-estradiol decreased the TRAIL expression levels in
      peripheral blood mononuclear cells. CONCLUSIONS: Our data suggest that 17beta
      estradiol plays a role in regulating TRAIL circulating levels. The demonstration
      that postmenopausal women exhibit the highest TRAIL levels is of particular
      interest in light of a previous large study population showing that TRAIL is
      positively correlated to the overall survival.

PMID- 24446660
TI  - Advances in target-specific therapy for osteoporosis.

PMID- 24446661
TI  - Copper sulfide self-assembly architectures with improved photothermal
      performance.
AB  - Copper chalcogenide nanomaterials are promising photothermal materials for
      establishing novel diagnostic and therapeutic methods owing to the low cost but
      high photothermal transduction efficiency. Further progresses of the correlated
      technologies greatly depend on the efforts on design and construction of novel
      nanostructures. In this paper, we demonstrate a facile one-pot route for
      constructing CuS nanostructures in aqueous media via a spontaneous assembly
      process. In the presence of polyvinylpyrrolidone (PVP) as the capping agents, a
      decomposition of Cu(CH3COSH)x precursors is induced by ammonia, which produces
      hexagonal CuS nanoparticles (NPs) with the diameter around 22 nm. The primary CuS
      NPs greatly tend to self-assembly into one-dimensional structures, which are
      triggered by short-range anisotropic dipolar attraction and enforced by long
      range isotropic electrostatic repulsion. The further fusion of the assembled NPs
      generates 480 * 50 nm(2) CuS nanorods. Because the formation of nanorods enhances
      the internanorod van der Waals attraction, the nanorods finally self-assembly
      into shuttle-like bundles in micrometer size. In comparison to isolated NPs, the
      regular CuS assembly structures exhibit improved molar extinction coefficient up
      to 9.7 * 10(16) cm(-1) M(-1) by shortening the distance of neighboring CuS NPs
      and therewith generating new electronic structures of the CuS indirect
      transition. Consequently, better photothermal performance is achieved. 

PMID- 24446662
TI  - Ontogenetic and spatiotemporal variability in anchoveta Engraulis ringens diet
      off Peru.
AB  - In this study, historical data available since 1954 were used to get new insight
      to ontogenetic and spatiotemporal variability in Peruvian anchovy or anchoveta
      Engraulis ringens diet. Whatever the period, E. ringens foraged mainly on
      macrozooplankton and the importance of euphausiids in E. ringens diet appears
      directly related to euphausiids abundance. This bottom-up effect is also observed
      at smaller scale because the euphausiids fraction increased with E. ringens total
      length and euphausiids accessibility. Selecting the largest prey, the
      euphausiids, provides an energetic advantage for E. ringens in its ecosystem
      where oxygen depletion imposes strong metabolic constraints on pelagic fishes.
      This study illustrates the plasticity of E. ringens that allows it to cope with
      its highly variable environment. 

PMID- 24446664
TI  - 2,4-Diaminothienopyrimidines as orally active antimalarial agents.
AB  - A novel series of 2,4-diaminothienopyrimidines with potential as antimalarials
      was identified from whole-cell high-throughput screening of a SoftFocus ion
      channel library. Synthesis and structure-activity relationship studies identified
      compounds with potent antiplasmodial activity and low in vitro cytotoxicity.
      Several of these analogues exhibited in vivo activity in the Plasmodium berghei
      mouse model when administered orally. However, inhibition of the hERG potassium
      channel was identified as a liability for this series. 

PMID- 24446663
TI  - Human-facilitated metapopulation dynamics in an emerging pest species, Cimex
      lectularius.
AB  - The number and demographic history of colonists can have dramatic consequences
      for the way in which genetic diversity is distributed and maintained in a
      metapopulation. The bed bug (Cimex lectularius) is a re-emerging pest species
      whose close association with humans has led to frequent local extinction and
      colonization, that is, to metapopulation dynamics. Pest control limits the
      lifespan of subpopulations, causing frequent local extinctions, and human
      facilitated dispersal allows the colonization of empty patches. Founder events
      often result in drastic reductions in diversity and an increased influence of
      genetic drift. Coupled with restricted migration, this can lead to rapid
      population differentiation. We therefore predicted strong population structuring.
      Here, using 21 newly characterized microsatellite markers and approximate
      Bayesian computation (ABC), we investigate simplified versions of two classical
      models of metapopulation dynamics, in a coalescent framework, to estimate the
      number and genetic composition of founders in the common bed bug. We found very
      limited diversity within infestations but high degrees of structuring across the
      city of London, with extreme levels of genetic differentiation between
      infestations (FST  = 0.59). ABC results suggest a common origin of all founders
      of a given subpopulation and that the numbers of colonists were low, implying
      that even a single mated female is enough to found a new infestation
      successfully. These patterns of colonization are close to the predictions of the
      propagule pool model, where all founders originate from the same parental
      infestation. These results show that aspects of metapopulation dynamics can be
      captured in simple models and provide insights that are valuable for the future
      targeted control of bed bug infestations. 

PMID- 24446665
TI  - The role of ultrasound in severity assessment in hidradenitis suppurativa.

PMID- 24446666
TI  - Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary
      alkyl halides at room temperature.
AB  - The development of a mild and general method for the alkylation of amides with
      relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is
      an ongoing challenge in organic synthesis. We describe herein a versatile
      transition-metal-catalyzed approach: in particular, a photoinduced, copper
      catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl
      amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated
      secondary (and hindered primary) alkyl bromides and iodides using a single set of
      comparatively simple and mild conditions: inexpensive CuI as the catalyst, no
      separate added ligand, and C-N bond formation at room temperature. The method is
      compatible with a variety of functional groups, such as an olefin, a carbamate, a
      thiophene, and a pyridine, and it has been applied to the synthesis of an opioid
      receptor antagonist. A range of mechanistic observations, including reactivity
      and stereochemical studies, are consistent with a coupling pathway that includes
      photoexcitation of a copper-amidate complex, followed by electron transfer to
      form an alkyl radical. 

PMID- 24446667
TI  - Longitudinal study of spherical refractive error in infantile nystagmus syndrome.
AB  - PURPOSE: To explore the onset and progression of spherical refractive error in a
      population with infantile nystagmus syndrome. METHODS: Retrospective refractive
      error data were obtained from 147 medical records of children with infantile
      nystagmus syndrome (albinism n = 98; idiopathic infantile nystagmus n = 49),
      attending a low vision clinic in Northern Ireland, over a 24 year period (1986
      2010). Data were categorised by age to allow for comparisons with published
      studies. A prospective group of participants with Infantile nystagmus syndrome
      (INS) [n = 22 (albinism n = 18, idiopathic infantile nystagmus n = 4)] (aged 0-4)
      were also recruited. Cycloplegic streak retinoscopy was performed biannually,
      over a 3 year period. Spherical equivalent refractive error and most ametropic
      meridian were analysed. RESULTS: The mean spherical equivalent refractive errors
      for albinism and idiopathic infantile nystagmus groups (across all age
      categories) were hypermetropic, with highest levels demonstrated by the
      participants with albinism aged 1 <= 4 years (Mann-Whitney U test, p = 0.013).
      Mean most ametropic meridian was highest in the albinism group aged 1 <= 12 years
      (Mann-Whitney U test, p < 0.05). Individual data demonstrated relatively static
      spherical equivalent refractive errors over time. Prospective participants were
      hypermetropic at all visits and those with albinism had, on average, higher
      refractive errors than those with idiopathic infantile nystagmus (IIN). No
      significant correlations were noted between visual acuity and spherical
      equivalent refractive errors or most ametropic meridian. CONCLUSIONS:
      Hypermetropia is the most prevalent spherical refractive error in the INS
      population, irrespective of level of visual acuity. Individuals with infantile
      nystagmus syndrome fail to demonstrate typical patterns of emmetropisation,
      particularly in the presence of albinism.

PMID- 24446668
TI  - Estimation of stage duration distributions and mortality under repeated cohort
      censuses.
AB  - Many processes in nature can be viewed as arising from subjects progressing
      through sequential stages and may be described by multistage models. Examples
      include disease development and the physiological development of plants and
      animals. We develop a multistage model for sampling designs where a small set of
      subjects is followed and the number of subjects in each stage is assessed
      repeatedly for a sequence of time points, but for which the subjects cannot be
      identified. The motivating problem is the laboratory study of developing
      arthropods through stage frequency data. Our model assumes that the same
      individuals are censused at each time, introducing among sample dependencies.
      This type of data often occur in laboratory studies of small arthropods but their
      detailed analysis has received little attention. The likelihood of the model is
      derived from a stochastic model of the development and mortality of the
      individuals in the cohort. We present an MCMC scheme targeting the posterior
      distribution of the times of development and times of death of individuals. This
      is a novel type of MCMC that uses customized proposals to explore a posterior
      with disconnected support arising from the fact that individual identities are
      unknown. The MCMC algorithm may be used for inference about parameters governing
      stage duration distributions and mortality rates. The method is demonstrated by
      fitting the development model to stage frequency data of a mealybug cohort placed
      on a grape vine.

PMID- 24446669
TI  - Hair iodine for human iodine status assessment.
AB  - BACKGROUND: Today, human iodine deficiency is, after iron, the most common
      nutritional deficiency in developed European and underdeveloped third world
      countries. A current biological indicator of iodine status is urinary iodine,
      which reflects very recent iodine exposure; a long-term indicator of iodine
      status remains to be identified. METHODS: We analyzed hair iodine in a
      prospective, observational, cross-sectional, and exploratory study involving 870
      apparently healthy Croatians (270 men and 600 women). Hair iodine was analyzed
      with inductively coupled plasma mass spectrometry. RESULTS: The hair iodine
      median was 0.499 MUg/g, and was 0.482 and 0.508 MUg/g for men and women
      respectively, suggesting no sex-related difference. We studied hair iodine uptake
      by analyzing the logistic sigmoid saturation curve of the median derivatives to
      assess iodine deficiency, adequacy, and excess. We estimated overt iodine
      deficiency to occur when hair iodine concentration was below 0.1-0.15 MUg/g. Then
      there was a saturation range interval of about 0.1-2.0 MUg/g where the deposition
      of iodine in the hair was linearly increasing (R(2)=0.994). Eventually, the
      sigmoid curve became saturated at about 2.0 MUg/g and upward, suggesting
      excessive iodine exposure. CONCLUSION: Hair appears to be a valuable and robust
      biological indicator tissue for assessing long-term iodine status. We propose
      that an adequate iodine status corresponds with hair iodine uptake saturation of
      0.565-0.739 MUg/g (55-65%).

PMID- 24446670
TI  - Preservation of the patent umbilical vein during a recipient hepatectomy: case
      report.
AB  - Clamping of the portal vein during a recipient hepatectomy during the anhepatic
      phase causes venous stagnation and hemodynamic instability. To prevent this, a
      temporary portocaval shunt is placed at some centers. This case report shows the
      patent umbilical vein of a patient undergoing a recipient hepatectomy, leading to
      a 20% reduction of pressure in the portal vein. Preservation of a patent
      umbilical vein may help prevent complications of high portal vein pressure during
      a recipient hepatectomy. 

PMID- 24446672
TI  - The Posttraumatic Growth Inventory: factor structure and invariance among persons
      with chronic diseases.
AB  - OBJECTIVE: The Posttraumatic Growth Inventory (PTGI) assesses positive changes
      after a traumatic or serious life crisis. However, there are differing views
      regarding its factor structure and little understanding if it captures the
      positive changes experienced among individuals diagnosed with a chronic disease.
      Using confirmatory factor analysis (CFA), the proposed five-factor structure and
      measurement invariance of the PTGI was examined using two chronic illness
      samples: arthritis and inflammatory bowel disease (IBD). METHOD: Individuals
      diagnosed with arthritis (n = 301) or IBD (n = 544) recruited from the community
      and the Internet completed the PTGI. Using a pooled sample, CFA tested five
      hypothesized models of the underlying factors structure of the PTGI. A stepwise
      procedure for testing the measurement invariance across the two groups evaluated
      the factor structure, factorial invariance, and latent mean invariance. RESULTS:
      Using the pooled sample, the CFA supported the hypothesized five-factor model,
      revealing the PTGI is multidimensional. Multigroup CFA supported invariance of
      the PTGI across the two groups although there were significant differences in
      latent means. CONCLUSIONS: The findings support that the PTGI assesses five
      related dimensions of PTG and that different chronic disease groups experience
      different types of positive changes. PTG may therefore be relevant as a
      meaningful treatment goal for people with chronic diseases as it is for people
      affected by other traumatic events.

PMID- 24446671
TI  - The rational patient and beyond: implications for treatment adherence in people
      with psychiatric disabilities.
AB  - OBJECTIVE: Many people with psychiatric disabilities do not benefit from evidence
      based practices because they often do not seek out or fully adhere to them. One
      way psychologists have made sense of this rehabilitation and health decision
      process and subsequent behaviors (of which adherence might be viewed as one) is
      by proposing a "rational patient"; namely, that decisions are made deliberatively
      by weighing perceived costs and benefits of intervention options. Social
      psychological research, however, suggests limitations to a rational patient
      theory that impact models of health decision making. DESIGN: The research
      literature was reviewed for studies of rational patient models and alternative
      theories with empirical support. Special focus was on models specifically related
      to decisions about rehabilitation strategies for psychiatric disability. RESULTS:
      Notions of the rational patient evolved out of several psychological models
      including the health belief model, protection motivation theory, and theory of
      planned behavior. A variety of practice strategies evolved to promote rational
      decision making. However, research also suggests limitations to rational
      deliberations of health. (1) Rather than carefully and consciously considered,
      many health decisions are implicit, potentially occurring outside awareness. (2)
      Decisions are not always planful; often it is the immediate exigencies of a
      context rather than an earlier balance of costs and benefits that has the
      greatest effects. (3) Cool cognitions often do not dictate the process; emotional
      factors have an important role in health decisions. Each of these limitations
      suggests additional practice strategies that facilitate a person's health
      decisions. CONCLUSION: Old models of rational decision making need to be
      supplanted by multiprocess models that explain supradeliberative factors in
      health decisions and behaviors.

PMID- 24446673
TI  - Physical activity among adults with obesity: testing the Health Action Process
      Approach.
AB  - OBJECTIVE: This study tested the applicability of the Health Action Process
      Approach (HAPA) in a sample of obese adults in the context of physical activity.
      METHOD: Physical activity was assessed along with motivational and volitional
      variables specified in the HAPA (motivational self-efficacy, outcome
      expectancies, risk perception, intention, maintenance self-efficacy, action
      planning, coping planning, recovery self-efficacy, social support) in a sample of
      484 obese men and women (body mass index >= 30 kg/m2). RESULTS: Applying
      structural equation modeling, the fit of the HAPA model was satisfactory
      chi2(191) = 569.93, p < .05, chi2/df = 2.98, comparative fit index = .91, normed
      fit index = .87, and root mean square error of approximation = .06 (90% CI = .06,
      .07)-explaining 30% of the variance in intention and 18% of the variance in
      physical activity. Motivational self-efficacy, outcome expectancies, and social
      support were related to intention. An association between maintenance self
      efficacy and coping planning was found. Recovery self-efficacy and social support
      were associated with physical activity. No relationships were found between risk
      perception and intention and between planning and physical activity. The
      assumptions derived from the HAPA were partly confirmed and the HAPA may,
      therefore, constitute a theoretical backdrop for intervention designs to promote
      physical activity in adults with obesity.

PMID- 24446674
TI  - Characterization and classification of pseudo-stationary phases in micellar
      electrokinetic chromatography using chemometric methods.
AB  - Two types of chemometric methods, principal component analysis (PCA) and cluster
      analysis, are employed to characterize and classify a total of 70
      pseudostationary phases (54 distinct systems and 16 decoy systems) in micellar
      electrokinetic chromatography (MEKC). PCA excels at removing redundant
      information for micellar phase characterization and retaining principal
      determinants for phase classification. While PCA is useful in the
      characterization of micelle selectivities, it is ineffective in defining the
      grouping of micellar phases. Hierarchical clustering yields a complete dendrogram
      of cluster structures but provides only limited cluster characterizations. The
      combination of these two chemometric methods leads to a comprehensive
      interpretation of the micellar phase classification. Moreover, the k-means
      analysis can further discern subtle differences among those closely located
      micellar phases. All three chemometric methods result in similar classifications
      with respect to the similarities and differences of the 70 micelle systems
      investigated. These systems are categorized into 3 major clusters: fluoro
      surfactants represent cluster I, identified as strong hydrogen bond donors and
      dipolar but weak hydrogen bond acceptors. Cluster II includes sulfonated
      acrylamide/acrylate copolymers and surfactants with trimethylammonium head
      groups, characterized by strong hydrophobicity (v) and weak hydrogen bond acidity
      (b). The last cluster consists of two subclusters: clusters III and IV. Cluster
      III includes siloxane-based polymeric micelles, exhibiting weak hydrophobicity
      and medium hydrogen bond acidity and basicity (a), and the cluster IV micellar
      systems are characterized by their strong hydrophobicity and medium hydrogen bond
      acidity and basicity but rather weak dipolarity. Cluster III differs from cluster
      IV by its slightly weaker hydrophobicity and hydrogen bond donating capability.
      The classification by chemometric methods is in good agreement with the
      classification by the micellar selectivity triangle (MST) ( Fu, C.; Khaledi, M.
      G. J. Chromatogr., A 2009 , 1216 , 1891 - 1900 ). 

PMID- 24446675
TI  - Evaluating charge transfer in epicocconone analogues: toward a targeted design of
      fluorophores.
AB  - Through-space charge transfers upon photon absorption in aminated epicocconone
      analogues, which serve as promising proteins markers, are investigated within
      time-dependent density functional theory using total densities differences and
      various point-charge models (with a special emphasis on Bader's atoms-in
      molecules theory). In particular, the distances and the amounts of charge
      transfer, as well as the transition dipole moments, are discussed from a
      methodological point of view, and their values are subsequently linked with the
      chemical structures of these efficient fluorophores. Finally, on the basis of
      these theoretical findings, several hints for the future improvement of the
      photochemical properties of these analogues are advanced. 

PMID- 24446676
TI  - A heteroleptic bis(tridentate) ruthenium(II) platform featuring an anionic 1,2,3
      triazolate-based ligand for application in the dye-sensitized solar cell.
AB  - A series of bis(tridentate) ruthenium(II) complexes featuring new anionic 1,2,3
      triazolate-based tridentate ligands and 2,2':6',2''-terpyridine is presented. For
      a complex equipped with carboxy anchoring groups, the performance in a dye
      sensitized solar cell is evaluated. The title complexes are readily synthesized
      and can be decorated with alkyl chains utilizing azide-alkyne cycloaddition
      methods, in order to improve the device stability and allow the use of
      alternative electrolytes. On account of the strong electron donation from the
      1,2,3-triazolates, the complexes exhibit a broad metal-to-ligand charge-transfer
      absorption (up to 700 nm), leading to an electron transfer toward the anchoring
      ligand. The lifetimes of the charge-separated excited states are in the range of
      50 to 80 ns. In addition, the ground- and excited-state redox potentials are
      appropriate for the application in dye-sensitized solar cells, as demonstrated by
      power conversion efficiencies of up to 4.9% (vs 6.1% for N749). 

PMID- 24446677
TI  - Interleukin-17A antagonist attenuates radiation-induced lung injuries in mice.
AB  - OBJECTIVE: To investigate the effect of interleukin-17A (IL-17A) antibodies on
      radiation-induced lung injuries in mice. METHODS: The thorax of 135 mice were
      divided into Sham (n = 30), radiation control (RC, n = 35), treatment (n = 35, IL
      17A-neutralizing antibody, 4 MUg/mouse, IV, 4 days per month for 4 months) and
      placebo group (n = 35) before a single dose irradiation (15 Gy) to the thorax.
      Inflammation and collagen contents in the lung tissues were examined, and the
      concentration of IL-17A, TGF-beta1, and IL-6 in bronchoalveolar lavage fluid
      (BALF) were measured. In another 50 animals, 180-day survival rate following the
      irradiation and treatment was calculated by Kaplan-Meier method. RESULTS: Sixteen
      weeks after the irradiation and treatment, there was significant inflammatory
      cell infiltration and interstitial collagen depositions in the radiation control
      and placebo groups, whereas these changes were relatively mild in the treatment
      group. The percentage of grade II and III alveolitis in the treatment group (16%,
      P < .05) was lower than in the RC (72%) or placebo group (64%). The mean
      Aschcroft fibrosis scores were 2.8 (treatment group), 5.2 (RC), and 4.8 (placebo
      group), respectively. The scores of treatment group was lower than that of RC (P
      < .001) or placebo group (P < .001). The IL-17A, TGF-beta, and IL-6
      concentrations in the treatment group were lower than in the RC and placebo group
      (P < .01) following the irradiation. The 180-day mortality rate in the treatment
      group was lower than in the RC group 16.7% versus 75.0%, P < .05). CONCLUSION: IL
      17A antibody treatment alleviates radiation-induced pneumonitis and subsequent
      fibrosis, and improvise postirradiation survival.

PMID- 24446682
TI  - Coarse-graining poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
      (PEO-PPO-PEO) block copolymers using the MARTINI force field.
AB  - The MARTINI coarse-grain (CG) force field is extended for a class of triblock
      block copolymers known as Pluronics. Existing MARTINI bead types are used to
      model the non-bonded part of the potential while single chain properties for both
      homopolymers, poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), are
      used to develop the bonded interactions. The new set of force field parameters
      reproduces structural and dynamical properties of high molecular weight homo- and
      copolymers. The CG model is moderately transferable in solvents of different
      polarity and concentration; however, the PEO homopolymer model presents a reduced
      thermodynamic transferability especially in water probably due to the lack of
      hydrogen bonds with the solvent. Our simulations of a monolayer of Pluronic L44
      show polymer-brush-like characteristics for the PEO segments which protrude into
      the aqueous phase. Other membrane properties not easily accessible using
      experimental techniques such as its membrane thickness are also calculated. 

PMID- 24446678
TI  - Studies toward communesin F: a Diels-Alder approach.
AB  - A Diels-Alder reaction is used as a key step in a synthetic study toward
      communesin F, in order to simultaneously introduce both of the all-carbon
      quaternary stereocenters with complete control of relative stereochemistry.
      Further manipulations of the cycloadduct, toward the hexacyclic core-structure of
      communesin F, are also disclosed. 

PMID- 24446683
TI  - Venous plasma serotonin is not a proper biomarker for pulmonary arterial
      hypertension.
AB  - OBJECTIVES: Serotonin (5-HT) most likely plays an important role in the
      pathogenesis of pulmonary arterial hypertension (PAH). We aimed to test if venous
      plasma 5-HT is a potential biomarker of PAH. We also measured venous blood beta
      thromboglobulin (beta-TG) in all participants to ensure that any increase in
      serotonin levels measured is due to platelet release. DESIGN: Blood samples from
      patients (n = 9) with pulmonary arterial hypertension (Group 1 of the World
      Health Organization classification of pulmonary hypertension) as well as healthy
      volunteers (n = 9) were analyzed. We used enzyme-linked immunosorbent assay
      (ELISA) to measure venous platelet-poor plasma 5-HT and beta-TG in patients with
      pulmonary arterial hypertension (PAH) and in age-matched normal controls.
      RESULTS: Venous platelet-free plasma 5-HT and beta-TG were almost similar in
      patients with PAH and healthy controls with only a slight trend toward increased
      5-HT levels in patients with PAH. No correlation was found between venous
      platelet-poor plasma 5-HT and disease severity. There was no association between
      venous plasma 5-HT and the mean pulmonary artery pressure. CONCLUSIONS: Our data
      suggest that 5-HT is not significantly elevated in venous platelet-free plasma in
      patients with PAH and may accordingly not be a useful biomarker in this
      condition.

PMID- 24446685
TI  - The role of action and coping planning in the relationship between intention and
      physical activity: a moderated mediation analysis.
AB  - OBJECTIVE: Using a moderated mediation model, the present study investigated
      whether the mediation of intention into physical activity (PA) behaviour via
      action planning depends on the level of coping planning. METHOD: A four-month
      prospective study was conducted among 157 French adults, who were recruited
      through a web-based survey. They were administrated measures of behavioural
      intention and sociodemographic variables at baseline and action and coping
      planning and PA four months later. RESULTS: Action planning partially mediated
      the contribution of intention on PA level. However, this indirect effect was
      conditional on the level of coping planning, insofar as action planning acted as
      a mediator of the intention-PA relationship only for individuals with high level
      of coping planning. CONCLUSION: The results highlight the complexity of the
      relationship between intention and behaviour and provide evidence for the
      distinct role of both forms of planning.

PMID- 24446686
TI  - Role of proinflammatory cytokines (interferon gamma) and anti-inflammatory
      cytokine (interleukin-10) gene polymorphisms in chronic hepatitis B infection: an
      Indian scenario.
AB  - Immune-mediated mechanisms have been found to play an important role in the
      progression of hepatitis B virus (HBV) infection. The outcomes of infection do
      not appear to be determined by viral strains. Instead, allelic variants in human
      genome are likely to affect the disease progression. Allelic variation of
      proinflammatory cytokines such as interferon gamma (IFN-gamma) participates in
      the elimination of HBV, and interleukin-10 (IL-10) helps in inhibition of Th1
      effector mechanisms for host defense. The aim of this study was to determine the
      influence of host genetic factors in chronic HBV infection and gene promoter
      polymorphism or single-nucleotide polymorphism analysis of IFN-gamma+874 and IL
      10 (-1082, -592, and -819) on disease progression and persistence. A total of 232
      patients along with 76 healthy controls were included. Allele-specific primers
      for IFN-gamma and restriction fragment length polymorphism for IL-10 were used.
      The study indicated that low IFN-gamma expression probably impairs host immune
      response to HBV, rendering these subjects more prone to HBV infection. No
      significant differences were detected between the 2 groups in the distributions
      of IL-10 genotype at the -1082, -819, and -592 positions. Odds ratio indicated
      that heterozygosity of genotypes -819 CT and -592 AC was more strongly associated
      with liver chronicity. Significantly, AA homozygous genotype was dominant in
      chronic hepatitis B cases in IFN-gamma+874 and IL-10 (-1082 and -592) and is
      associated with increased risk of persistent infection. 

PMID- 24446687
TI  - Development of a particle nanoimprinting technique by core-shell particles.
AB  - We developed a particle nanoimprinting technique assisted by the array of core
      shell particles. Core-shell particles composed of a solid core of polystyrene and
      a soft shell were prepared by soap-free emulsion polymerization and subsequently
      seeded polymerization. By the Langmuir-Blodgett method, particles were arranged
      into a closely packed 2D array over the water surface and transferred onto a
      polystyrene (PS) substrate at a regular interval. The PS substrate was heated up
      above its glass transition temperature (Tg) by either UV irradiation using a high
      pressure Hg lamp or heat treatment in a temperature-controlled incubator. It
      could be observed that a nanopatterned indented surface was formed through the
      denting of particles into the PS substrate (particle nanoindenting). By the
      detachment of particles from the substrate by ultrasonication in ethanol,
      nanoholes were produced over the surface (particle nanoimprinting). The depth and
      the wall of nanoholes and their interval were tunable by the shell thickness and
      the 2D packing ratio of core-shell particle monolayers. The contact angle
      decreased from 70 degrees of the pristine particle monolayer to 13 degrees by the
      particle nanoindenting, and again increased to 50 degrees by detaching the
      particles from the substrate to create the nanoholes. The use of nanoholes as
      zepto-litter volume vessels enabled us to produce and arrange nanocrystals, such
      as NaCl and CaCO3 (zepto-reactor). 

PMID- 24446688
TI  - Discovery and development of simeprevir (TMC435), a HCV NS3/4A protease
      inhibitor.
AB  - Hepatitis C virus is a blood-borne infection and the leading cause of chronic
      liver disease (including cirrhosis and cancer) and liver transplantation. Since
      the identification of HCV in 1989, there has been an extensive effort to identify
      and improve treatment options. An important milestone was reached in 2011 with
      the approval of the first-generation HCV NS3/4A protease inhibitors. However, new
      therapies are needed to improve cure rates, shorten treatment duration, and
      improve tolerability. Here we summarize the extensive medicinal chemistry effort
      to develop novel P2 cyclopentane macrocyclic inhibitors guided by HCV NS3
      protease assays, the cellular replicon system, structure-based design, and a
      panel of DMPK assays. The selection of compound 29 (simeprevir, TMC435) as
      clinical candidate was based on its excellent biological, PK, and safety
      pharmacology profile. Compound 29 has recently been approved for treatment of
      chronic HCV infection in combination with pegylated interferon-alpha and
      ribavirin in Japan, Canada, and USA. 

PMID- 24446689
TI  - Carbonic anhydrase-related protein VIII antibodies and paraneoplastic cerebellar
      degeneration.

PMID- 24446690
TI  - Left ventricular remodeling and dysfunction in systemic lupus erythematosus: a
      three-dimensional speckle tracking study.
AB  - OBJECTIVE: To analyze left ventricular (LV) global structure and systolic
      function in patients with systemic lupus erythematosus (SLE) using the three
      dimensional (3D) speckle tracking imaging. METHODS: Thirty-four SLE patients and
      34 healthy subjects underwent 3D echocardiography to obtain LV ejection fraction
      (LVEF), sphericity index, 3D LV mass, 3D global longitudinal strain (GLS), global
      circumferential strain (GCS), global area strain (GAS), and global radial strain
      (GRS). Disease activity was evaluated for all SLE patients by SLEDAI 2000 (SLEDAI
      2K) score. RESULTS: Age, gender, height, weight, diastolic blood pressure, and
      two-dimensional (2D) LVEF were similar between the 2 groups. Despite no
      difference was found for sphericity index between the groups, 3D LV mass was
      increased in SLE patients. All components of strain were significantly reduced in
      SLE patients. Peak systolic GLS, GCS, GAS, and GRS in SLE patients and controls
      were -18.2 +/- 2.9% versus -21.4 +/- 2.5%, -18.4 +/- 3.1% versus -20.6 +/- 2.5%, 
      32.2 +/- 4.4% versus -36.6 +/- 3.4%, and 51.4 +/- 10.2% versus 61.9 +/- 10.0%,
      respectively (all P < 0.01). In multivariable regression analysis, SLE was
      independently associated with GAS (P < 0.001). In SLE patients, peak systolic
      GLS, GAS, GRS was significantly decreased in those with severe disease activity
      than among inactivity/mildly activity (all P < 0.05). GLS was independently
      correlated with SLEDAI score (P = 0.001). CONCLUSION: Three-dimensional speckle
      tracking imaging is a new simple, rapid method to indentify early abnormalities
      in SLE patients who may have normal LV systolic function with 2D
      echocardiography.

PMID- 24446691
TI  - Editorial comment from Dr Hsiao to Prognostic impact of young age on stage IV
      prostate cancer treated with primary androgen deprivation therapy.

PMID- 24446693
TI  - Viral suppression in HIV studies: combining times to suppression and rebound.
AB  - In HIV-1 clinical trials the interest is often to compare how well treatments
      suppress the HIV-1 RNA viral load. The current practice in statistical analysis
      of such trials is to define a single ad hoc composite event which combines
      information about both the viral load suppression and the subsequent viral
      rebound, and then analyze the data using standard univariate survival analysis
      techniques. The main weakness of this approach is that the results of the
      analysis can be easily influenced by minor details in the definition of the
      composite event. We propose a straightforward alternative endpoint based on the
      probability of being suppressed over time, and suggest that treatment differences
      be summarized using the restricted mean time a patient spends in the state of
      viral suppression. A nonparametric analysis is based on methods for multiple
      endpoint studies. We demonstrate the utility of our analytic strategy using a
      recent therapeutic trial, in which the protocol specified a primary analysis
      using a composite endpoint approach.

PMID- 24446694
TI  - The effect of loading palladium on zinc oxide on the photocatalytic degradation
      of methyl tert-butyl ether (MTBE) in water.
AB  - A series of heterogeneous catalysts was prepared by doping zinc oxide with
      different palladium loadings in the range of 0.5%-1.5%. The prepared catalysts
      were characterized by SEM, TEM and XRD. These catalysts were applied to study the
      degradation of Methyl tert-Butyl Ether (MTBE). An amount of 100 mg of each of
      these catalysts was added to an aqueous solution of 100 ppm of MTBE. The
      resulting mixtures were irradiated with UV light for a period of 5 h. A 99.7%
      removal of MTBE was achieved in the case of the zinc oxide photocatalyst
      particles doped with 1% Pd. The photoreaction was found to be a first-order one. 

PMID- 24446695
TI  - Comparison of the prevalence of surgical site infection with use of sterile
      versus nonsterile gloves for resection and reconstruction during Mohs surgery.
AB  - BACKGROUND: The prevalence of surgical site infection (SSI) is low with Mohs
      micrographic surgery (MMS). It has not been determined whether sterile gloves
      (SG) or nonsterile gloves (NSG) should be used for resection and reconstruction
      during MMS. OBJECTIVE: To compare the SSI rate with the use of SG and NSG for
      MMS, including reconstruction, and to determine whether SG help prevent SSI.
      MATERIALS & METHODS: Data were collected and recorded for Mohs cases in which SG
      or NSG were used. Infected cases and SSI rate for SG and NSG were also recorded.
      Chi-square analysis was performed to compare SSI. RESULTS: There were 1,004
      tumors in 942 patients in the SG group and 1,021 tumors in 941 patients in the
      NSG group. The prevalence of infection was 0.50% in the SG group and 0.49% in the
      NSG group (p = .82). The cost of gloves was $5.66 for one SG case and $1.63 for
      one NSG case. CONCLUSION: The prevalence of infection with SG and NSG was almost
      identical. The cost to use SG was 3.5 times as great as for NSG. The use of NSG
      for MMS and reconstruction is safe and cost effective.

PMID- 24446696
TI  - Comparative demography of commercially important parrotfish species from
      Micronesia.
AB  - Fishery-independent sampling was used to determine growth patterns, life span,
      mortality rates and timing of maturation and sex change in 12 common parrotfishes
      (Labridae: tribe Scarinae) from five genera (Calotomus, Cetoscarus, Chlorurus,
      Hipposcarus and Scarus) in Micronesia. Interspecific variation in life-history
      traits was explored using multivariate analysis. All species displayed strong sex
      specific patterns of length-at-age among which males reached larger asymptotic
      lengths. There was a high level of correlation among life-history traits across
      species. Relationships between length-based and age-based variables were weakest,
      with a tenuous link between maximum body size and life span. Cluster analysis
      based on similarities among life-history traits demonstrated that species were
      significantly grouped at two major levels. The first grouping was driven by
      length-based variables (lengths at maturity and sex change and maximum length)
      and separated the small- and large-bodied species. Within these, species were
      grouped by age-based variables (age at maturity, mortality and life span).
      Groupings based on demographic and life-history features were independent of
      phylogenetic relationships at the given taxonomic level. The results reiterate
      that body size is an important characteristic differentiating species, but
      interspecific variation in age-based traits complicates its use as a life-history
      proxy. Detailed life-history metrics should facilitate future quantitative
      assessments of vulnerability to overexploitation in multispecies fisheries. 

PMID- 24446697
TI  - Gamna-Gandy bodies: a case of mistaken identity in the spleen of a cat.
AB  - A 4-year-old, female spayed Domestic Shorthair cat was presented for a 2-day
      history of lethargy, anorexia, and vomiting. Diagnostic assessments revealed a
      severe, regenerative anemia and the presence of a solitary, 3 * 4 cm splenic
      mass. Cytologic examination of fine-needle aspirates of the splenic mass showed
      sheets of pleomorphic histiocytic cells with numerous intracellular and
      extracellular, negatively staining to deeply basophilic, branching structures.
      These structures were typically of thin uniform thickness with random angled
      branching that formed geometrical shapes and fragments, occasionally with
      sharpened ends and a crystalline appearance. Septal-like divisions were
      irregularly spaced along some of the linear branches. The cytology was
      interpreted as a probable histiocytic inflammatory response to the unidentified
      foreign material with histiocytic sarcoma as a differential diagnosis.
      Histopathologic evaluation of the splenic mass resulted in a diagnosis of
      histiocytic sarcoma. The branching material stained positively for both iron and
      calcium, indicating that the material was compatible with Gamna-Gandy bodies
      present secondary to tumor-associated hemorrhage and the formation of calcium
      iron complexes.

PMID- 24446698
TI  - Nickel-catalyzed site-selective alkylation of unactivated C(sp3)-H bonds.
AB  - The direct alkylation of unactivated sp(3) C-H bonds of aliphatic amides was
      achieved via nickel catalysis with the assist of a bidentate directing group. The
      reaction favors the C-H bonds of methyl groups over the methylene C-H bonds and
      tolerates various functional groups. Moreover, this reaction shows a predominant
      preference for sp(3) C-H bonds of methyl groups via a five-membered ring
      intermediate over the sp(2) C-H bonds of arenes in the cyclometalation step. 

PMID- 24446699
TI  - Sampling capacity underlies individual differences in human associative learning.
AB  - Though much work has studied how external factors, such as stimulus properties,
      influence generalization of associative strength, there has been limited
      exploration of the influence that internal dispositions may contribute to
      stimulus processing. Here we report 2 studies using a modified negative
      patterning discrimination to test the relationship between global processing and
      generalization. Global processing was associated with stronger negative
      patterning discrimination, indicative of limited generalization between distinct
      stimulus compounds and their constituent elements. In Experiment 2, participants
      pretrained to adopt global processing similarly showed strong negative patterning
      discrimination. These results demonstrate considerable individual difference in
      capacity to engage in negative patterning discrimination and suggest that the
      tendency toward global processing may be one factor explaining this variability.
      The need for models of learning to account for this variability in learning is
      discussed.

PMID- 24446700
TI  - Polylactide-graft-doxorubicin nanoparticles with precisely controlled drug
      loading for pH-triggered drug delivery.
AB  - Nanoparticles (NPs) with high drug loading and pH-responsivity were prepared by
      nanoprecipitation of a hydrophobic polymer-drug conjugate (PDC). The PDC,
      polylactide-graft-doxorubicin (PLA-g-DOX), was synthesized by azide-alkyne click
      reaction to transform acetylene-functionalized PLA into PLA-graft-aldehyde (PLA-g
      ALD), followed by DOX conjugation to form acid-sensitive Schiff base linkage
      between drug moieties and polymer scaffold. The DOX loading amount in PLA-g-DOX
      PDC was determined to be 32 wt % by (1)H NMR and UV-vis spectroscopies. PLA-g-DOX
      PDC was further used to prepare NPs with precisely controlled drug loading by
      nanoprecipitation in the presence of a PEGylated surfactant. The effects of
      organic solvent, PLA-g-DOX PDC concentration and PLA-g-DOX/surfactant mass ratio
      on size and size distribution of NPs were systematically examined based on
      analysis by dynamic light scattering (DLS) and transmission electron microscopy
      (TEM). NPs prepared under the optimal conditions exhibited well-defined spherical
      morphology with volume-average hydrodynamic diameter (Dh) around 100 nm. Due to
      the Schiff base conjugation linkage in PLA-g-DOX PDC, acid-sensitive drug release
      behavior of the NPs was observed. In vitro studies against MCF-7 breast cancer
      cells showed that the NPs can be readily taken up and result in enhanced
      therapeutic efficiency as compared to DOX.HCl, indicating their promising
      potential applications as anticancer nanomedicines. 

PMID- 24446701
TI  - 193 nm ultraviolet photodissociation mass spectrometry for the structural
      elucidation of lipid A compounds in complex mixtures.
AB  - Here we implement ultraviolet photodissociation (UVPD) in an online liquid
      chromatographic tandem mass spectrometry (MS/MS) strategy to support analysis of
      complex mixtures of lipid A combinatorially modified during development of
      vaccine adjuvants. UVPD mass spectrometry at 193 nm was utilized to characterize
      the structures and fragment ion types of lipid A from Escherichia coli, Vibrio
      cholerae, and Pseudomonas aeruginosa using an Orbitrap mass spectrometer. The
      fragment ions generated by UVPD were compared to those from collision induced
      dissociation (CID) and higher energy collision dissociation (HCD) with respect to
      the precursor charge state. UVPD afforded the widest array of fragment ion types
      including acyl chain C-O, C-N, and C-C bond cleavages and glycosidic C-O and
      cross ring cleavages, thus providing the most comprehensive structural analysis
      of the lipid A. UVPD exhibited virtually no dependence on precursor ion charge
      state and was best at determining lipid A structure including acyl chain length
      and composition, giving it an advantage over collision based methods. UVPD was
      incorporated into an LC-MS/MS methodology for the analysis of a number of
      structural variants in a complex mixture of combinatorially engineered
      Escherichia coli lipid A. 

PMID- 24446703
TI  - Conjugate-base-stabilized Bronsted acids: catalytic enantioselective Pictet
      Spengler reactions with unmodified tryptamine.
AB  - A conjugate-base-stabilized Bronsted acid facilitates catalytic enantioselective
      Pictet-Spengler reactions with unmodified tryptamine. The chiral carboxylic acid
      catalyst is readily assembled in just two steps and enables the formation of beta
      carbolines with up to 92% ee. Achiral acid additives or in situ Boc-protection
      facilitate catalyst turnover. 

PMID- 24446704
TI  - Reversible switching of coordination mode of ansa bis(amidinate) ligand in
      ytterbium complexes driven by oxidation state of the metal atom.
AB  - Reaction of bisamidine C6H4-1,2-{NC(t-Bu)NH(2,6-Me2C6H3)}2 (1) and
      [(Me3Si)2N]2Yb(THF)2 (THF = tetrahydrofuran) (toluene; room temperature) in a 1:1
      molar ratio afforded a bis(amidinate) Yb(II) complex [C6H4-1,2-{NC(t-Bu)N(2,6
      Me2C6H3)}2]Yb(THF) (2) in 65% yield. Complex 2 features unusual kappa(1)amide,
      eta(6)-arene coordination of both amidinate fragments to the ytterbium ion,
      resulting in the formation of a bent bis(arene) structure. Oxidation of 2 by
      Ph3SnCl (1:1 molar ratio) or (PhCH2S)2 (1:0.5) leads to the Yb(III) species [C6H4
      1,2-{NC(t-Bu)N(2,6-Me2C6H3)}2]YbCl(1,2-dimethoxyethane) (3) and {[C6H4-1,2-{NC(t
      Bu)N(2,6-Me2C6H3)}2]Yb(MU-SCH2Ph)}2 (4), performing "classic" kappa(2)N,N'
      chelating coordination mode of ansa bis(amidinate) ligand. By the reduction of 3
      with equimolar amount of sodium naphthalide [C10H8(*-)][Na(+)] in THF, complex 2
      can be recovered and restored to a bent bis(arene) structure. Complex 3 was also
      synthesized by the salt metathesis reaction of equimolar amounts of YbCl3 and the
      dilithium derivative of 1 in THF. 

PMID- 24446702
TI  - Titer dynamic analysis of D29 within MTB-infected macrophages and effect on
      immune function of macrophages.
AB  - The use of mycobacteriophage D29 to treat Mycobacterium tuberculosis (MTB)
      infected macrophages results in significant inhibitory activity. This study aims
      to explore the novel treatment strategy of intracellular mycobacterial infection
      from the point of view of phages. We investigated the dynamic phagocytosis and
      elimination of D29 by macrophages, measured the titer of D29 inside and outside
      MTB within macrophages by fluorescence quantitative PCR, and detected the levels
      of interleukin 12 (IL-12) and nitric oxide (NO) in the culture supernatants of
      D29-infected macrophages by ELISA. Results showed that the activity of D29
      phagocytosed by macrophages was significantly lower than that of D29 phagocytosed
      by MTB-infected macrophages. The titer of D29 that infected intracellular MTB
      ranged from 10(9) pfu to 10(4) pfu. The titer of D29 inside and outside
      intracellular MTB transiently increased when MTB-infected macrophages were
      incubated with D29 for 40 and 50 min; then, a large number of D29 were eliminated
      by macrophages. The levels of IL-12 and NO had no significant differences versus
      the negative control but were significantly lower compared with the
      lipopolysaccharide (LPS) positive control. These results suggest D29 has no
      effect on the immune function of macrophages and that high phage titer must be
      administered repeatedly if D29 is applied to treat intracellular MTB infection.

PMID- 24446706
TI  - En bloc kidney transplant from young pediatric donors: a scope to increase the
      donor pool.
AB  - We report 2 cases of en bloc kidney transplants from young pediatric donors with
      successful outcomes. We underscore the underuse of this significant donor source,
      and discuss the factors that may be related to the reasons for reluctance in
      accepting these kidneys for transplant. 

PMID- 24446705
TI  - Pharmacokinetics of equol, a soy isoflavone metabolite, changes with the form of
      equol (dietary versus intestinal production) in ovariectomized rats.
AB  - Recent findings indicate that soy isoflavones and their metabolites may play a
      role in mitigating postmenopausal bone loss. Equol, a metabolite of the soy
      isoflavone daidzein produced by intestinal bacteria, has shown some potential,
      but only 30-50% of the U.S. population is capable of converting dietary daidzein
      to equol. There are limited data on the pharmacokinetics of dietary racemic equol
      and its metabolites. This study was conducted to assess the levels of equol and
      its conjugates in plasma for a 24 h period resulting from oral administration of
      dietary daidzein and racemic equol in ovariectomized Sprague-Dawley rats. Plasma
      samples were analyzed for conjugated and free forms of equol using LC-MS/MS. The
      maximum plasma concentration (C(max)) and time to reach it (t(max)) for total
      equol (conjugated and unconjugated) were 8815 +/- 2988 nmol/L and 2.17 +/- 2.91 h
      and 3682 +/- 2675 nmol/L and 20.67 +/- 4.67 h, for dietary equol and daidzein,
      respectively. Although the majority of equol metabolites present were glucuronide
      conjugates (>=99%), there were low levels of equol monosulfate present. The
      changes in equol metabolism, specifically equol conjugates, due to the form of
      equol may play a role in the potential health benefits of equol.

PMID- 24446708
TI  - Immune-mediated necrotizing myopathies are serologically heterogeneous and
      autoantibodies may predict their clinical phenotype: two cases associated with
      anti-Pl7 antibodies.

PMID- 24446709
TI  - The role of the cation in the solvation of cellulose by imidazolium-based ionic
      liquids.
AB  - We present a systematic molecular dynamics study examining the roles of the
      individual ions of different alkylimidazolium-based ionic liquids in the
      solvation of cellulose. We examine combinations of chloride, acetate, and
      dimethylphosphate anions paired with cations of increasing tail length to
      elucidate the precise role of the cation in solvating cellulose. In all cases we
      find that the cation interacts with the nonpolar domains of cellulose through
      dispersion interactions, while interacting electrostatically with the anions
      bound at the polar domains of cellulose. Furthermore, the structure and
      dimensions of the imidazolium head facilitate the formation of large chains and
      networks of alternating cations and anions that form a patchwork, satisfying both
      the polar and nonpolar domains of cellulose. A subtle implication of increasing
      tail length is the dilution of the anion concentration in the bulk and at the
      cellulose surface. We show how this decreased concentration of anions in the bulk
      affects hydrogen bond formation with cellulose and how rearrangements from single
      hydrogen bonds to multiple shared hydrogen bonds can moderate the loss in overall
      hydrogen bond numbers. Additionally, for the tail lengths examined in this study
      we observe only a very minor effect of tail length on the solvation structure and
      overall interaction energies. 

PMID- 24446710
TI  - The echocardiographic paradox index in patients with a repaired tetralogy of
      Fallot.
AB  - OBJECTIVES: Right ventricular (RV) volume is very important for pulmonary valve
      replacement after the total correction of tetralogy of Fallot (TOF), and we
      attempted to identify a convenient echocardiographic index that is well
      correlated with the volumetric data obtained through magnetic resonance imaging
      (MRI). DESIGN: All patients who underwent cardiac MRI and echocardiography at
      Sejong General Hospital for evaluating pulmonary regurgitation after TOF total
      correction were included. The paradox index is the amount of paradoxical motion
      of the interventricular septum on the short-axis echocardiographic view. The
      paradox index was compared to several cardiac MRI indices. RESULTS: Fifty-four
      patients were included. The paradox index for all patients was 1.22 +/- 0.12
      (1.06-1.67), and the index of the operation group was significantly higher than
      that of the non-operation group (1.26 +/- 1.12 vs 1.16 +/- 1.12, P = 0.009). The
      paradox index was well correlated with the RV systolic and diastolic volumes, as
      measured by cardiac MRI (P = 0.002 and 0.003). Using a simple linear regression
      analysis, a paradox index of 1.24 corresponded to a RV diastolic volume of 160
      ml/m(2). CONCLUSIONS: The paradox index could help to indicate the time for an
      MRI analysis of the RV volume in patients after TOF total correction.

PMID- 24446711
TI  - Cytotoxicity of coated and uncoated fibre-reinforced composites.
AB  - OBJECTIVE: Currently, there are many fibre-reinforced composites (FRCs) available
      which differ in the type and volume fraction of fibres, pre-treatment of fibres
      and matrix composition. The aims of this in vitro investigation were to determine
      whether there is a difference in biocompatibility of FRCs and if coating FRCs
      with resin composites influences their cytotoxic potential. MATERIALS AND
      METHODS: Five different FRC materials were tested which were either uncoated or
      coated with flowable or viscous resin composite. Artificial saliva extracts were
      prepared according to USP-XXIII and ISO-10993 to determine cytotoxicity by
      testing cell viability and growth of primary human gingival fibroblasts (HGF)
      using MTT assay, LIVE/DEAD((r)) assay and cell proliferation assay. The influence
      of eluates on fibres of the cytoskeleton was investigated by vimentin, tubulin
      and actinin immunostainings. A two-way ANOVA followed by Scheffe's post-hoc test,
      which included the factors FRC material and coating procedure, was performed to
      assess cytotoxicity. RESULTS: All extracts of FRC materials displayed minor
      cytotoxic potential on HGF cell viability, cell proliferation and integrity of
      the cytoskeleton. The type of FRC material significantly influenced cell
      viability (MTT assay) (p < 0.0001), whereas neither the presence of a coating nor
      the type of coating material resulted in altered cell viability. Distribution and
      organization of cytosolic fibres was not affected after HGF exposure to eluates.
      CONCLUSIONS: There is a lack of knowledge about the leaching behaviour of
      commonly available fully pre-impregnated FRCs and their interactions with coating
      materials. The coating of FRCs with resin composite materials did not impact
      biocompatibility.

PMID- 24446712
TI  - Interactions in mixed micellar systems of an amphoteric chelating surfactant and
      ionic surfactants.
AB  - Mixtures of ionic surfactants and the chelating surfactant 2
      dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) have been examined in
      terms of interactions in mixed micellar systems. The amphoteric 4-C12-DTPA is
      zwitterionic with a negative net charge at the studied pH levels. The
      investigated ionic surfactants were the cationic dodecyltrimethylammonium
      chloride (DoTAC), the anionic sodium dodecyl sulfate (SDS), and the zwitterionic
      dimethyldodecylamine-N-oxide (DDAO). The surfactants all have the same
      hydrophobic chain lengths, and the results are evaluated in terms of headgroup
      interactions. 4-C12-DTPA interacts with different ionic surfactants by accepting
      or donating protons to the aqueous solution to increase the attractive
      interactions between the two surfactants; i.e., the protonation equilibrium of 4
      C12-DTPA is shifted in different directions depending on whether there are
      predominant repulsions between positively or negatively charged groups in the
      mixed micelles. This was monitored by measuring pH vs concentration in the mixed
      systems. By measuring the pH, it was also possible to study the shift in the
      protonation equilibrium at increasing concentration, as the composition in the
      micelles approaches the composition in the total solution. Following the approach
      of Rubingh's regular solution theory, the interaction parameter beta for mixed
      micelle formation was calculated from the cmc values determined by NMR
      diffusometry. Synergism in mixed micelle formation and negative beta parameters
      were found in all of the investigated systems. As expected, the most negative
      beta parameter was found in the mixture with DoTAC, followed by DDAO and SDS. The
      self-diffusion in the 4-C12-DTPA/DoTAC system was also discussed. The self
      diffusion coefficient vs concentration plots show two distinctly different
      curves, depending on the surfactant that is present in excess. 

PMID- 24446713
TI  - The psychosocial predictors of long-term distress in partners of patients with
      acute coronary syndrome.
AB  - OBJECTIVE: Partners of acute coronary syndrome (ACS) patients are at risk of
      experiencing long-term distress and the purpose of this study was to identify its
      predictors. DESIGN: Using an observational design, 80 partners of ACS patients
      completed validated questionnaires at three time points. The predictor variables,
      marital satisfaction and optimism were assessed three weeks after patient
      hospital discharge (T1). The outcomes, depressive symptoms and physical health
      status (from a quality of life scale) were measured 6 (T2) and 12 (T3) months
      post-discharge, and scores were combined to indicate the long-term response. MAIN
      OUTCOME MEASURES: Depressive symptoms and physical health status. RESULTS:
      Partner depressive symptoms increased and physical health status deteriorated
      over the months following the patients' ACS. After controlling for demographics,
      clinical severity of ACS and T1 levels of the outcome variable, partners' long
      term depressive symptoms were predicted by poor marital satisfaction and low
      optimism at T1, and poor physical health status was predicted by low T1 optimism.
      CONCLUSION: Psychosocial factors are predictors of long-term distress for ACS
      partners. Partners in an unhappy marriage or with low optimism after ACS are at
      an increased risk of depression and low physical health status, and should be the
      target of additional support.

PMID- 24446716
TI  - Cor triatriatum dexter, atrial septal defects, and pulmonary stenosis-a rare
      association.
AB  - Cor triatriatum dexter (CTD) is an extremely rare congenital anomaly in which the
      right atrium is divided into 2 chambers by a membrane. The estimated incidence of
      cor triatriatum has been reported as 0.1% of congenital cardiac malformations.
      The septation of the right atrium in the setting of CTD is the result of failed
      resorption of the right valve of the sinus venosus. This results in anterolateral
      and posteromedial portions of the divided right atrium. CTD can be diagnosed at
      any age, especially if it is incidentally discovered. 

PMID- 24446717
TI  - From sound to shape: auditory perception of drawing movements.
AB  - This study investigates the human ability to perceive biological movements
      through friction sounds produced by drawings and, furthermore, the ability to
      recover drawn shapes from the friction sounds generated. In a first experiment,
      friction sounds, real-time synthesized and modulated by the velocity profile of
      the drawing gesture, revealed that subjects associated a biological movement to
      those sounds whose timbre variations were generated by velocity profiles
      following the 1/3 power law. This finding demonstrates that sounds can adequately
      inform about human movements if their acoustic characteristics are in accordance
      with the kinematic rule governing actual movements. Further investigations of our
      ability to recognize drawn shapes were carried out in 2 association tasks in
      which both recorded and synthesized sounds had to be associated to both distinct
      and similar visual shapes. Results revealed that, for both synthesized and
      recorded sounds, subjects made correct associations for distinct shapes, although
      some confusion was observed for similar shapes. The comparisons made between
      recorded and synthesized sounds lead to conclude that the timbre variations
      induced by the velocity profile enabled the shape recognition. The results are
      discussed in the context of the ecological and ideomotor frameworks.

PMID- 24446718
TI  - Attention on the source of influence reverses the impact of cross-contextual
      imitation.
AB  - Recent investigations of imitation have demonstrated that individuals imitate a
      primed movement across contexts. For example, when tasting a drink, individuals
      who observe an athlete lifting a barbell raise their arms to their mouths more
      often, thus increasing their drink intake because both actions (i.e., weight
      lifting and drinking) involve the same movements. Other research on semantic
      priming suggests that individuals often act in the opposite direction of the
      primed information when their attention is directed toward the source of
      influence. In one experiment, we tested whether focusing participants' attention
      on the source of influence leads to such correction processes in a cross
      contextual imitation setting as well. Replicating the basic cross-contextual
      imitation effect, we found that participants whose attention was not directed
      toward the source of influence drank more when observing an athlete lifting a
      barbell than when observing an athlete pushing a barbell. However, when
      participants' attention was directed toward the source of influence, they acted
      in the opposite direction so strongly that they drank more when watching the
      pushing movement than when watching the lifting movement.

PMID- 24446721
TI  - Two-photon circular dichroism of an axially dissymmetric diphosphine ligand with
      strong intramolecular charge transfer.
AB  - In this article we report on the study of the polarization dependent two-photon
      absorption (TPA) of (S)-(+)-(1,1'-binaphthalene-2,2'-diyl)bis(diphenylphosphine)
      (S-BINAP) in solution, and the theoretical-experimental analysis of its two
      photon circular dichroism (TPCD) spectrum. The comparative examination of the
      following two correlation functionals, using the 6-31G* basis set, showed that
      the Coulomb attenuated method variant of the Becke's three-parameter exchange and
      the Lee-Yang-Parr (CAM-B3LYP) is more reliable than B3LYP in molecules such as S
      BINAP, a heteroaromatic diphosphine chiral ligand with strong intramolecular
      charge transfer. To access the theoretical TPCD spectra, we employed time
      dependent density functional theory (TD-DFT) at the mentioned level of theory and
      over the first 40 electronic excited states including solvent effects by means of
      the polarizable continuum model (PCM). The extended calculation on twice as many
      electronic excited states in vacuo proved to be crucial for the correct
      assignment of the experimental bands. TPA measurements were performed in the
      femtosecond regime and over a broad spectral range using the double L-scan
      technique. 

PMID- 24446719
TI  - Measuring psychometric functions with the diffusion model.
AB  - The diffusion decision model (Ratcliff, 1978) was used to examine discrimination
      for a range of perceptual tasks: numerosity discrimination, number
      discrimination, brightness discrimination, motion discrimination, speed
      discrimination, and length discrimination. The model produces a measure of the
      quality of the information that drives decision processes, a measure termed drift
      rate in the model. As drift rate varies across experimental conditions that
      differ in difficulty, a psychometric function that plots drift rate against
      difficulty can be constructed. Psychometric functions for the tasks in this
      article usually plot accuracy against difficulty, but for some levels of
      difficulty, accuracy can be at ceiling. The diffusion model extends the range of
      difficulty that can be evaluated because drift rates depend on response times
      (RTs) as well as accuracy, and when RTs decrease across conditions that are all
      at ceiling in accuracy, then drift rates will distinguish among the conditions.
      Signal detection theory assumes that the variable driving performance is the z
      transform of the accuracy value, and, somewhat surprisingly, this closely matches
      drift rate extracted from the diffusion model when accuracy is not at ceiling,
      but not sometimes when accuracy is high. Even though the functions are similar in
      the middle of the range, the interpretations of the variability in the models
      (e.g., perceptual variability, decision process variability) are incompatible.

PMID- 24446722
TI  - Multiple highly and moderately differentiated squamous cell carcinomas of the
      skin during vismodegib treatment of inoperable basal cell carcinoma.

PMID- 24446720
TI  - Collective variable approaches for single molecule flexible fitting and enhanced
      sampling.

PMID- 24446723
TI  - A phase II, randomized, placebo-controlled, double-blind, multi-dose study of
      SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.
AB  - AIM: SRT2104 is a selective activator of SIRT1. In animal models, SRT2104
      improves glucose homeostasis and increases insulin sensitivity. We evaluated the
      tolerability and pharmacokinetics of SRT2104, and its effects on glycaemic
      control, in adults with type 2 diabetes mellitus. METHOD: Type 2 diabetics with
      glycosylated haemoglobin (HbA1c) >= 7.5% and <=10.5%, fasting glucose >=160 and
      <=240 mg dl(-1) , and on stable doses of metformin were evenly randomized to
      placebo or SRT2104 0.25 g, 0.5 g, 1.0 g or 2.0 g, administered orally once daily
      for 28 days. Changes in fasting and post-prandial glucose and insulin were
      analyzed. RESULTS: Safety evaluation found no major differences between groups in
      the frequency of adverse events. SRT2104 concentrations did not increase in a
      dose-proportional fashion. Significant variability in exposure was observed.
      Treatment with SRT2104 did not lead to any consistent, dose-related changes in
      glucose or insulin. Day 28 change from baseline (mean (SD)): fasting glucose
      (mmol l(-1) ) = -1.17 (2.42), -1.11 (3.45), -0.52 (2.60), -0.97 (2.83) and -0.15
      (2.38) for placebo, 0.25 g, 0.5 g, 1.0 g and 2.0 g, respectively. Day 28 change
      from baseline (mean (SD)): fasting insulin (mmol l(-1) ) = 1.0 (51.66), 8.9
      (95.04), -6.9 (41.45), 4.1 (57.16) and 15.2 (138.79) for placebo, 0.25 g, 0.5 g,
      1.0 g and 2.0 g, respectively) Treatment with SRT2104 was associated with
      improvement in lipid profiles. CONCLUSION: Treatment with SRT2104 for 28 days did
      not result in improved glucose or insulin control which is likely due to the
      observed pharmacokinetics which were not dose proportional and had large between
      subject variability.

PMID- 24446724
TI  - Analysis of photoexcitation energy dependence in the photoluminescence of firefly
      luciferin.
AB  - The whole pathways for photoluminescence, which include absorption, relaxation
      and emission, of firefly luciferin in aqueous solutions of different pH values
      with different photoexcitation energies were theoretically investigated by
      considering protonation/deprotonation. It is experimentally known that the color
      of fluorescence changes from green to red with a decrease in the photoexcitation
      energy. We confirmed with the theoretical analysis that the peak energy shift in
      the fluorescence spectra with varying photoenergies is due to a change in
      photoluminescence pathway. When the photoexcitation energy is decreased, the red
      emission from a monoanion form of firefly luciferin with carboxylate and
      phenolate groups and N-protonated thiazoline ring occurs irrespective of the pH
      values. However, because the species abundant in the solution and those excited
      by the photon depend on the solution pH, the pathway leading to the monoanion
      form changes with the solution pH. 

PMID- 24446725
TI  - Effect of mechanical forces on finger nail curvature: an analysis of the effect
      of occupation on finger nails.
AB  - BACKGROUND: We studied the relationship between mechanical force and nail
      curvature. METHODS: The effect of different frequencies and strengths of
      mechanical force on nail curvature was assessed. In Study 1, 63 carpenters and 63
      office workers were enrolled, and the configurations of their thumb nails were
      assessed by measuring the curve index (defined as nail height/width) and pinch
      strength. In Study 2, nail curvature and pinch strength of jazz bassists, who
      characteristically do not use the right fourth and fifth fingers but use the left
      fifth finger a lot, were compared. In Study 3, the thumb nail curvature and pinch
      strength of the dominant and nondominant sides of the 126 participants from Study
      1 were compared. RESULTS: Study 1: Carpenters had a significantly lower mean
      thumb nail curve index and higher mean pinch strength. Study 2: The nails of the
      unused right fourth and fifth fingers were much more curved than the nails of the
      frequently used left fourth and fifth fingers. The pinch strength of the right
      fifth finger was much weaker than the pinch strength of the left fifth finger.
      Study 3: The dominant side had a significantly lower nail curve index and higher
      pinch strength. CONCLUSION: The frequency and strength of mechanical forces on
      finger nails significantly affect nail appearance.

PMID- 24446726
TI  - Association between interleukin 18 polymorphisms and alopecia areata in Koreans.
AB  - Interleukin 18 (interferon gamma-inducing factor) (IL18) is an important
      proinflammatory cytokine that belongs to the IL1 family. This study investigated
      whether IL18 single-nucleotide polymorphisms (SNPs) are associated with the
      susceptibility to alopecia areata (AA) in a Korean population. Two hundred thirty
      three AA patients and 243 healthy control subjects were recruited. One promoter
      SNP (rs187238, -137G/C) and exonic SNP (rs549908, Ser35Ser) in IL18 were
      genotyped using direct sequencing. SNPStats, SPSS 18.0, and Haploview version 4.2
      programs were used to evaluate genetic data. Multiple logistic regression models
      were used to determine odds ratios, 95% confidence intervals, and P values.
      Tested 2 SNPs (rs187238 and rs549908) were associated with the development of AA
      (rs187238, P=0.002 in a codominant model 1, P=0.0048 in a dominant model, P=0.02
      in a log-additive model, P=0.023 in allele distribution; rs549908, P=0.003 in a
      codominant model 1, P=0.0052 in a dominant model, P=0.016 in a log-additive
      model, P=0.015 in allele distribution). Our data suggest that the IL18 may be a
      risk factor for AA susceptibility.

PMID- 24446727
TI  - Carboxymethyl cellulose film as a substrate for microarray fabrication.
AB  - Magnetic beads (MB) are widely used for quick and highly sensitive signal
      detection in microarray-based assays. However, this technique imposes stringent
      requirements for smoothness and adhesive properties of the surface, which most
      common substrates do not satisfy. We report here a new type of substrate for
      microarrays with a low adhesion to MB-thermally cross-linked carboxymethyl
      cellulose (CMC) film. This substrate can be readily fabricated on a conventional
      glass slide. A highly cross-linked CMC film (~1 cross-link per monomer unit)
      possesses a surface smooth on a nanometer scale and a low adhesion to protein
      coated MB, which partly originates from electrostatic repulsion of MB from
      negatively charged CMC surface. The efficiency of the CMC substrate is
      demonstrated hereby in fabrication of microarrays for the detection of three
      bacterial toxins: cholera toxin, staphylococcal enterotoxin A, and toxic shock
      syndrome toxin. The assay employing a primary antibodies arrayed on a CMC surface
      and detection of the bound bacterial toxins with a biotinylated secondary
      antibodies and streptavidin-coated MB resulted in a limits of detection as low as
      0.1 ng/mL. The CMC-based microarrays demonstrated very high storage stability;
      their activity did not change after one year storage at room temperature. 

PMID- 24446728
TI  - Glucocorticoid receptor modulators informed by crystallography lead to a new
      rationale for receptor selectivity, function, and implications for structure
      based design.
AB  - The structural basis of the pharmacology enabling the use of glucocorticoids as
      reliable treatments for inflammation and autoimmune diseases has been augmented
      with a new group of glucocorticoid receptor (GR) ligands. Compound 10, the
      archetype of a new family of dibenzoxepane and dibenzosuberane sulfonamides, is a
      potent anti-inflammatory agent with selectivity for the GR versus other steroid
      receptors and a differentiated gene expression profile versus clinical
      glucocorticoids (lower GR transactivation with comparable transrepression). A
      stereospecific synthesis of this chiral molecule provides the unique topology
      needed for biological activity and structural biology. In vivo activity of 10 in
      acute and chronic models of inflammation is equivalent to prednisolone. The
      crystal structure of compound 10 within the GR ligand binding domain (LBD)
      unveils a novel binding conformation distinct from the classic model adopted by
      cognate ligands. The overall conformation of the GR LBD/10 complex provides a new
      basis for binding, selectivity, and anti-inflammatory activity and a path for
      further insights into structure-based ligand design. 

PMID- 24446729
TI  - The clinical utility of two human portable blood glucose meters in canine and
      feline practice.
AB  - BACKGROUND: Portable blood glucose meters (PBGMs) are useful for serial
      measurements of blood glucose and creation of blood glucose curves in veterinary
      practice. However, it is necessary to validate PBGMs designed for people for
      veterinary use. OBJECTIVES: Our objective was to evaluate the accuracy of 2 PBGMs
      designed for people for use in dogs and cats. METHODS: The blood glucose levels
      were determined in blood samples collected from 69 dogs and 26 cats admitted to
      the Kagoshima University Veterinary Teaching Hospital, using a MEDISAFE [PBGM-T]
      and an Antsense III [PBGM-H], and a FUJI DRI-CHEM 7000V as reference method. The
      correlations and agreements among the results were statistically analyzed.
      RESULTS: Simple regression analyses revealed a high correlation between values
      from both PBGMs and the reference method in both dogs and cats. However, Passing
      Bablok regression and Bland-Altman analyses revealed that the data from both
      PBGMs did not show statistical agreement with the reference values. Concordance
      correlated coefficients were moderate for the PBGM-T and almost perfect for the
      PBGM-H for canine samples, and were poor for the PBGM-T and substantial for the
      PBGM-H for feline samples. Hematocrit values significantly affected the results
      of the PBGM-T, but not the PBGM-H. Error grid analyses revealed that all
      measurements from both PBGMs would lead to acceptable treatment decisions.
      CONCLUSIONS: Our findings suggest that both PBGMs, especially the PBGM-H, would
      be clinically useful in small animal practice, although there was a bias between
      each PBGM and the reference method.

PMID- 24446730
TI  - A new species of Astyanax Baird & Girard (Characiformes: Characidae) from the Rio
      Paraguacu basin, Chapada Diamantina, Bahia, Brazil, with comments on bony hooks
      on all fins.
AB  - A new species of Astyanax from the Rio Paraguacu basin, Bahia, Brazil, is
      described. This new species is distinguished from its congeners known to occur in
      Brazilian drainages by the presence of small bony hooks on all fins of mature
      males. Furthermore, the new species can be diagnosed by its colour pattern, which
      consists of a unique vertically elongated humeral blotch, a conspicuous dark drop
      shaped horizontal blotch over the caudal peduncle, tapering anteriorly and not
      extending to the median caudal-fin rays, and by the absence of a conspicuous
      broad dark midlateral stripe. The new species differs further by having the
      greatest body depth just anterior to the dorsal-fin origin, 32-35 perforated
      scales in the lateral line and a reduced number of branched anal-fin rays (16
      20). Apparently, the new species does not fit into any species complex of
      Astyanax. The occurrence of bony hooks on all fins of Astyanax is discussed. 

PMID- 24446731
TI  - To B or not to B? Glucocorticoid impact on B lymphocyte fate and function.

PMID- 24446734
TI  - Alternating 2,6-/3,5-substituted pyridine-acetylene macrocycles: pi-stacking self
      assemblies enhanced by intermolecular dipole-dipole interaction.
AB  - Macrocyclic compounds consisting of three 2,6-pyridylene and three 3,5-pyridylene
      units linked by acetylene bonds were synthesized by a Sonogashira reaction. The X
      ray structures showed pi-stacked pairs of two macrocycles, in which a 2,6
      pyridylene unit of the one molecule overlaps a 3,5-pyridylene of the other
      molecule because of dipole-dipole interaction. Atomic force microscope (AFM)
      measurements revealed fibril structures indicating the stacking of the rigid
      planar macrocycles. Hydrogen-bonding ability of the macrocyclic inside was
      demonstrated by the addition of octyl beta-D-glucopyranoside.

PMID- 24446735
TI  - Control of L-type ferrimagnetism by the Ce/vacancy ordering in the A-site-ordered
      perovskite Ce(1/2)Cu3Ti4O12.
AB  - A-site-ordered perovskite Ce1/2Cu3Ti4O12 has been found to crystallize in two
      different forms, one with random and the other with ordered Ce/vacancy
      distribution at the A site of the prototype AA'3B4O12 structure. The random phase
      is isostructural with CaCu3Ti4O12, and the ordered phase is a new ordered
      derivative of the AA'3B4O12-type perovskite with two crystallographically
      distinct Cu sites. Although both phases form a G-type antiferromagnetic
      arrangement of Cu(2+) spins below 24 K, their magnetisms are quite different. A
      typical antiferromagnetic transition is observed in the random phase, whereas a
      small ferromagnetic moment appears below 24 K in the ordered phase, which rapidly
      decreases upon further cooling. A mean-field approximation approach revealed that
      this unusual behavior in the ordered phase is an L-type ferrimagnetism driven by
      the nonequivalent magnetizations of the two ferromagnetic Cu(2+) spin sublattices
      in the G-type spin structure. This unusual ferrimagnetism is a direct consequence
      of the Ce/vacancy ordering. 

PMID- 24446738
TI  - Change in CXCL10 on treatment with methotrexate similar to that reported with
      infliximab: comments on the article by Eriksson et al.

PMID- 24446736
TI  - Induction of lung cancer cell apoptosis through a p53 pathway by [6]-shogaol and
      its cysteine-conjugated metabolite M2.
AB  - Dietary chemoprevention of cancer offers the possibility to suppress or inhibit
      cancer growth before it develops into more advanced and lethal stages. To this
      end, identification of novel compounds and their mechanisms of action is
      constantly needed. In this study, we describe that a major component of dry
      ginger (Zingiber officinalis), [6]-shogaol (6S), can be quickly metabolized in
      A549 human lung cancer cell line. One of the resulting metabolites, the cysteine
      conjugated 6S (M2), exhibits toxicity to cancer cells similar to the parent
      compound 6S, but is relatively less toxic toward normal cells than 6S. We further
      demonstrate that both compounds can cause cancer cell death by activating the
      mitochondrial apoptotic pathway. Our results show that the cancer cell toxicity
      is initiated by early modulation of glutathione (GSH) intracellular content. The
      subsequently generated oxidative stress activates a p53 pathway that ultimately
      leads to the release of mitochondria-associated apoptotic molecules such as
      cytochrome C, and cleaved caspases 3 and 9. In a xenograft nude mouse model, a
      dose of 30 mg/kg of 6S or M2 was able to significantly decrease tumor burden,
      without any associated toxicity to the animals. This effect was correlated with
      an induction of apoptosis and reduction of cell proliferation in the tumor
      tissues. Taken together, our results show that 6S metabolism is an integral part
      of its anticancer activities in vitro and in vivo. This allows us to characterize
      M2 as a novel compound with superior in vivo chemopreventive properties that
      targets similar anticancer mechanisms as 6S. 

PMID- 24446739
TI  - BRAF inhibitor therapy for melanoma, thyroid and colorectal cancers: development
      of resistance and future prospects.
AB  - BRAF is a major oncoprotein and oncogenic mutations in BRAF are found in a
      significant number of cancers, including melanoma, thyroid cancer, colorectal
      cancer and others. Consequently, BRAF inhibitors have been developed as treatment
      options for cancers with BRAF mutations which have shown some success in
      improving patient outcomes in clinical trials. Development of resistance to BRAF
      kinase inhibitors is common, however, overcoming this resistance is an area of
      significant concern for clinicians, patients and researchers alike. In this
      review, we identify the mechanisms of BRAF kinase inhibitor resistance and
      discuss the implications for strategies to overcome this resistance in the
      context of new approaches such as multi-kinase targeted therapies and emerging
      RNA interference based technologies. 

PMID- 24446740
TI  - Optimizing electrostatic field calculations with the Adaptive Poisson-Boltzmann
      Solver to predict electric fields at protein-protein interfaces II: explicit near
      probe and hydrogen-bonding water molecules.
AB  - We have examined the effects of including explicit, near-probe solvent molecules
      in a continuum electrostatics strategy using the linear Poisson-Boltzmann
      equation with the Adaptive Poisson-Boltzmann Solver (APBS) to calculate electric
      fields at the midpoint of a nitrile bond both at the surface of a monomeric
      protein and when docked at a protein-protein interface. Results were compared to
      experimental vibrational absorption energy measurements of the nitrile
      oscillator. We examined three methods for selecting explicit water molecules: (1)
      all water molecules within 5 A of the nitrile nitrogen; (2) the water molecule
      closest to the nitrile nitrogen; and (3) any single water molecule hydrogen
      bonding to the nitrile. The correlation between absolute field strengths with
      experimental absorption energies were calculated and it was observed that method
      1 was only an improvement for the monomer calculations, while methods 2 and 3
      were not significantly different from the purely implicit solvent calculations
      for all protein systems examined. Upon taking the difference in calculated
      electrostatic fields and comparing to the difference in absorption frequencies,
      we typically observed an increase in experimental correlation for all methods,
      with method 1 showing the largest gain, likely due to the improved absolute
      monomer correlations using that method. These results suggest that, unlike with
      quantum mechanical methods, when calculating absolute fields using entirely
      classical models, implicit solvent is typically sufficient and additional work to
      identify hydrogen-bonding or nearest waters does not significantly impact the
      results. Although we observed that a sphere of solvent near the field of interest
      improved results for relative field calculations, it should not be consider a
      panacea for all situations. 

PMID- 24446742
TI  - Conducting-interlayer SiOx memory devices on rigid and flexible substrates.
AB  - SiOx memory devices that offer significant improvement in switching performance
      were fabricated at room temperature with conducting interlayers such as Pd, Ti,
      carbon, or multilayer graphene. In particular, the Pd-interlayer SiOx memory
      devices exhibited improvements in lowering the electroforming voltages and
      threshold voltages as the number of inserted Pd layers was increased, as compared
      to a pure SiOx memory structure. In addition, we demonstrated that the Pd
      interlayer SiOx junction fabricated on a flexible substrate maintained low
      electroforming voltage and mechanically stable switching properties. From these
      observations, a possible switching mechanism is discussed based on the formation
      of individual conducting paths at the weakest edge regions of each SiOx film,
      where the normalized bond-breaking probability of SiOx is influenced by the
      voltage and the thickness of SiOx. This fabrication approach offers a useful
      structural platform for next-generation memory applications for enhancement of
      the switching properties while maintaining a low-temperature fabrication method
      that is even amenable with flexible substrates. 

PMID- 24446744
TI  - Administration of adjuvant oxaliplatin to patients with stage III colon cancer is
      affected by age and hospital.

PMID- 24446743
TI  - Human papilloma virus detection and typing in 334 lung cancer patients.
AB  - BACKGROUND: Unlike cervical, anogenital and oropharyngeal cancers, where high
      risk human papillomavirus (hrHPV) has long been known to play a major role, a
      causative link between HPV and lung cancer has been investigated for decades with
      discrepant results. METHODS: Lung cancer patients eligible for surgical treatment
      were tested for the presence of HPV-DNA in excised, fresh frozen lung tumor
      tissue. Patients that tested positive were further examined for the presence of
      HPV-DNA in adjacent normal lung parenchyma. HPV detection and genotyping was
      performed using a polymerase chain reaction (PCR)-based approach and allowed the
      typing of 13 "high-risk"-HPV-types and 2 "low-risk"-HPV-types. RESULTS: Of the
      334 tumor-DNA samples tested, 13 (3.9%) showed presence of HPV-DNA, of which 12
      were of a high-risk HPV type (16, 33, 66). In those tested positive, HPV-DNA was
      not found in adjacent normal lung tissue. No correlation with smoking or
      EGFR/KRAS mutation status was seen, and only one of 84 squamous cell carcinomas
      was HPV-positive. CONCLUSION: We conclude that HPV is rarely associated with lung
      cancer in a Northern European population and in those tested positive, more
      functional studies are required to determine the role HPV plays in lung cancer
      oncogenesis.

PMID- 24446745
TI  - Severe dental erosion associated with imatinib mesylate therapy.

PMID- 24446747
TI  - Poly(dimethylsiloxane)-stabilized polymer particles from radical dispersion
      polymerization in nonpolar solvent:influence of stabilizer properties and monomer
      type [corrected].
AB  - Particles used in electrophoretic display applications (EPD) must possess a
      number of specific properties ranging from stability in a nonaqueous solvent,
      high reflectivity, low polydispersity, and high charge density to name but a few.
      The manufacture of such particles is best carried out in the solvent of choice
      for the EPD. This opens up new interests in the study of nonaqueous dispersion
      polymerization methods, which deliver polymer particles suspended in low
      dielectric constant solvents. We explore in this article the use of a
      poly(dimethylsiloxane) macromonomer for the stabilization of poly(methyl
      methacrylate) polymer particles in dodecane, a typical solvent of choice for
      EPDs. The use of this stabilizer is significant for this method as it is directly
      soluble in the reaction medium as opposed to traditionally used poly(12
      hydroxystearic acid)-based stabilizers. Additionally, the present study serves as
      a baseline for subsequent work, where nonaqueous dispersion polymerization will
      be used to create polymer particles encapsulating liquid droplets and solid
      pigment particles. In this article, the influence of the macromonomer molecular
      weight and concentration on the properties of the synthesized particles is
      studied. In addition, we investigate the possibility of synthesizing polymer
      particles from other monomers both as a comonomer for methyl methacrylate and as
      the only monomer in the process. The influence of macromonomer concentration is
      also studied throughout all experiments. 

PMID- 24446748
TI  - Multifaceted roles of disulfide bonds. Peptides as therapeutics.

PMID- 24446749
TI  - Prospective study of formalin-fixed Mohs surgery and haematoxylin and eosin
      stains with control contralateral biopsies for lentigo maligna: 5-year follow-up
      results.
AB  - BACKGROUND: There is little consensus on the optimum form of surgical management
      for lentigo maligna (LM). Currently, because malignant melanocytes spread down
      adnexal structures, full-thickness skin removal is the only surgical option.
      Interpretation of Mohs histological specimens is difficult because of the
      presence of abnormal melanocytes in otherwise normal sun-damaged skin.
      OBJECTIVES: To investigate Slow Mohs for surgical excision of LM, to see whether
      the use of control contralateral skin biopsies would enable the end point of
      excision to be more easily interpreted and to investigate factors that influence
      the subclinical amelanotic extensions of LM. METHODS: The Slow Mohs technique for
      formalin-fixed tissue was used in 74 patients with LM. Before surgery LMs were
      classified as well defined, poorly defined, incompletely excised or recurrent.
      Control biopsies were taken from healthy skin of the contralateral side.
      Specimens were processed in formalin, stained with haematoxylin and eosin (H&E)
      and the results read at 24-48 h. The excision margin required for complete
      excision was measured and patients were followed for a minimum of 5 years to
      exclude recurrence. RESULTS: On average the final excision margin required was
      6.7 mm. Margins were significantly greater for ill-defined, recurrent and
      incompletely excised LM compared with well-defined LM. The presence of
      depigmented patches preoperatively did not correlate with the excision margin,
      but LMs showing nesting required significantly wider excision margins. There were
      seven (12%) recurrences at a mean 4.4 years after surgery in the group with 5
      year follow-up. Recurrence occurred only in recurrent and ill-defined primary LM.
      CONCLUSIONS: The use of Slow Mohs formalin-fixed tissue and H&E section staining,
      even with comparator biopsies, does not provide sufficient discrimination to
      identify residual disease confidently.

PMID- 24446750
TI  - Coexisting bicuspid aortic and pulmonary valves with normally related great
      vessels diagnosed by live/real time three-dimensional transesophageal
      echocardiography.
AB  - Coexistence of bicuspid aortic and pulmonary valves in the same patient is a very
      rare entity identified mainly during surgery and postmortem. To the best of our
      knowledge, only one case has been diagnosed by two-dimensional echocardiography
      in a newborn with malposition of the great arteries but no images were presented.
      Here, we are reporting the first case of bicuspid pulmonary and aortic valves
      diagnosed by live/real time three-dimensional transesophageal echocardiography in
      an adult with normally related great arteries. 

PMID- 24446751
TI  - Quantum mechanical basis for kinetic diameters of small gaseous molecules.
AB  - Kinetic diameters are often invoked in discussing gas adsorption and permeation
      in porous and polymeric materials. However, how these empirical kinetic diameters
      relate to the size and shape of the molecules as manifested by their "electron
      cloud" is unclear. In this paper, we obtain the quantum mechanical (QM) diameters
      of several common gaseous molecules by determining the cross-sectional sizes of
      their iso-electronic density surfaces at a predetermined small value. We show
      that the QM diameters are in good agreement with the kinetic diameters. For
      example, the trends for important gas pairs such as O2 versus N2 and CO2 versus
      N2 are consistent between the QM diameters and the most often quoted kinetic
      diameters. Hence, our work now provides a quantum mechanical basis for the
      empirical kinetic diameters and will be useful for designing separation media for
      small gaseous molecules according to their sizes. 

PMID- 24446752
TI  - Working memory updating latency reflects the cost of switching between
      maintenance and updating modes of operation.
AB  - Updating and maintenance of information are 2 conflicting demands on working
      memory (WM). We examined the time required to update WM (updating latency) as a
      function of the sequence of updated and not-updated items within a list.
      Participants held a list of items in WM and updated a variable subset of them in
      each trial. Four experiments that vary the number of to-be-updated and to-be
      maintained items, as well as their positions in the list, are reported. The
      pattern of latencies was best explained by a model assuming forward scanning of
      the list, updating modified items, and maintaining nonmodified items. Switching
      between updating and maintenance incurred a response time cost, which increased
      with overall set-size. The formation of new item-position associations accounted
      for an additional response time component. The finding of an update-switch cost
      provides novel behavioral support for a class of physiologically inspired
      computational models, in which updating and maintenance require 2 different
      states of WM.

PMID- 24446753
TI  - Evidence evaluation: measure Z corresponds to human utility judgments better than
      measure L and optimal-experimental-design models.
AB  - Evidence evaluation is a crucial process in many human activities, spanning from
      medical diagnosis to impression formation. The present experiments investigated
      which, if any, normative model best conforms to people's intuition about the
      value of the obtained evidence. Psychologists, epistemologists, and philosophers
      of science have proposed several models to account for people's intuition about
      the utility of the obtained evidence with respect either to a focal hypothesis or
      to a constellation of hypotheses. We pitted against each other the so-called
      optimal-experimental-design models (i.e., Bayesian diagnosticity, log10
      diagnosticity, information gain, Kullback-Leibler distance, probability gain, and
      impact) and measures L and Z to compare their ability to describe humans'
      intuition about the value of the obtained evidence. Participants received words
      and-numbers scenarios concerning 2 hypotheses and binary features. They were
      asked to evaluate the utility of "yes" and "no" answers to questions about some
      features possessed in different proportions (i.e., the likelihoods) by 2 types of
      extraterrestrial creatures (corresponding to 2 mutually exclusive and exhaustive
      hypotheses). Participants evaluated either how an answer was helpful or how an
      answer decreased/increased their beliefs with respect either to a single
      hypothesis or to both hypotheses. We fitted mixed-effects models and used the
      Akaike information criterion and the Bayesian information criterion values to
      compare the competing models of the value of the obtained evidence. Overall, the
      experiments showed that measure Z was the best fitting model of participants'
      judgments of the value of obtained answers. We discussed the implications for the
      human hypothesis-evaluation process.

PMID- 24446754
TI  - Executive control modulates cross-language lexical activation during L2 reading:
      evidence from eye movements.
AB  - Models of bilingual reading such as Bilingual Interactive Activation Plus
      (Dijkstra & van Heuven, 2002) do not predict a central role for domain-general
      executive control during bilingual reading, in contrast with bilingual models
      from other domains, such as production (e.g., the Inhibitory Control Model;
      Green, 1998). We thus investigated whether individual differences among
      bilinguals in domain-general executive control modulate cross-language activation
      during L2 sentence reading, over and above other factors such as L2 proficiency.
      Fifty French-English bilinguals read L2-English sentences while their eye
      movements were recorded, and they subsequently completed a battery of executive
      control and L2 proficiency tasks. High- and low-constraint sentences contained
      interlingual homographs (chat = "casual conversation" in English, "a cat" in
      French), cognates (piano in English and French), or L2-specific control words.
      The results showed that greater executive control among bilinguals but not L2
      proficiency reduced cross-language activation in terms of interlingual homograph
      interference. In contrast, increased L2 proficiency but not executive control
      reduced cross-language activation in terms of cognate facilitation. These results
      suggest that models of bilingual reading must incorporate mechanisms by which
      domain-general executive control can alter the earliest stages of bilingual
      lexical activation.

PMID- 24446755
TI  - A randomized controlled study of the effects of different modalities of narrow
      band ultraviolet B therapy on the outcome of cultured autologous melanocytes
      transplantation in treating vitiligo.
AB  - BACKGROUND: Vitiligo is an acquired skin disorder with great social impact. It
      can be successfully treated using cultured autologous melanocytes
      transplantation. OBJECTIVE: To evaluate the effect of different modalities of
      narrow-band ultraviolet B (NB-UVB) therapy on the outcome of cultured autologous
      melanocyte transplantation in treating vitiligo. METHODS: Patients undergoing
      cultured autologous melanocyte transplantation were randomly assigned to four
      different study groups. Group 1 underwent 20 sessions of NB-UVB treatment before
      transplantation; Group 2 underwent 30 sessions of NB-UVB treatment after
      transplantation; Group 3 underwent 20 sessions of NB-UVB treatment before
      transplantation and 30 sessions after transplantation; Group 4 underwent only
      transplantation. RESULTS: Four hundred thirty-seven patients were enrolled. Group
      3 responded best, more than 90% repigmentation was achieved in 81.3% of patients,
      and 94.8% patients experienced 50% or greater repigmentation. Statistical
      analysis showed that there was a highly significant difference between the four
      groups (chi(2) = 35.56, p < .001). Homogeneous skin color was obtained on the
      repigmentation areas, and no scarring or other serious side effects were
      observed. CONCLUSIONS: Cultured autologous melanocyte transplantation is an
      effective treatment for stable vitiligo. Combination of NB-UVB therapy with
      melanocyte transplantation can accelerate repigmentation of transplanted
      vitiliginous areas, especially if NB-UVB is given before and after
      transplantation.

PMID- 24446756
TI  - Accumulation, selection and covariation of amino acids in sieve tube sap of tansy
      (Tanacetum vulgare) and castor bean (Ricinus communis): evidence for the function
      of a basic amino acid transporter and the absence of a gamma-amino butyric acid
      transporter.
AB  - Sieve tube sap was obtained from Tanacetum by aphid stylectomy and from Ricinus
      after apical bud decapitation. The amino acids in sieve tube sap were analyzed
      and compared with those from leaves. Arginine and lysine accumulated in the sieve
      tube sap of Tanacetum more than 10-fold compared to the leaf extracts and they
      were, together with asparagine and serine, preferably selected into the sieve
      tube sap, whereas glycine, methionine/tryptophan and gamma-amino butyric acid
      were partially or completely excluded. The two basic amino acids also showed a
      close covariation in sieve tube sap. The acidic amino acids also grouped
      together, but antagonistic to the other amino acids. The accumulation ratios
      between sieve tube sap and leaf extracts were smaller in Ricinus than in
      Tanacetum. Arginine, histidine, lysine and glutamine were enriched and
      preferentially loaded into the phloem, together with isoleucine and valine. In
      contrast, glycine and methionine/tryptophan were partially and gamma-amino
      butyric acid almost completely excluded from sieve tube sap. The covariation
      analysis grouped arginine together with several neutral amino acids. The acidic
      amino acids were loaded under competition with neutral amino acids. It is
      concluded from comparison with the substrate specificities of already
      characterized plant amino acid transporters, that an AtCAT1-like transporter
      functions in phloem loading of basic amino acids, whereas a transporter like
      AtGAT1 is absent in phloem. Although Tanacetum and Ricinus have different minor
      vein architecture, their phloem loading specificities for amino acids are
      relatively similar. 

PMID- 24446757
TI  - Initial responses to the first dose of nicotine in novel smokers: the role of
      exposure to environmental smoking and genetic predisposition.
AB  - BACKGROUND: Sensitivity to initial smoking constitutes an early predictor of the
      risk of dependence. We investigated the role of exposure to smoking (by parents,
      siblings, and peers) and reward-related candidate gene polymorphisms (OPRM1
      A118G, DRD2 TaqlA and DRD4 bp VNTR) in adolescents' responses to initial smoking.
      METHODS: We used cross-sectional survey data and saliva samples from 171 Dutch
      students who had never inhaled on a cigarette (mean age: 13.9 years). The outcome
      measure was adolescents' self-reported responses to initial smoking. RESULTS:
      Exposure to peer smoking was associated with increased liking (OR = 1.74, CI =
      1.13-2.70) and more pleasant sensations (beta = .21, p = .01). Exposure to
      maternal smoking was associated with less unpleasant sensations (beta = -.20, p =
      .01). Adolescents carrying the G-variant of the OPRM1 A118G polymorphism were
      more likely to report liking (OR = 2.50, CI = 1.09-5.73) and adolescents
      homozygous for the C-variant of the DRD2 TaqlA polymorphism reported less
      unpleasant sensations (beta = .18, p = .04). CONCLUSION: Although preliminary,
      these findings suggest that exposure to environmental smoking and polymorphisms
      in the OPRM1 and DRD2 gene may affect initial sensitivity to nicotine, an early
      phenotype of the risk of dependence. In the future, collaborative efforts to
      combine data from multiple studies in meta-analyses are needed to improve
      accuracy of estimated effects in genetic studies.

PMID- 24446758
TI  - Highly sensitive and selective strategy for microRNA detection based on WS2
      nanosheet mediated fluorescence quenching and duplex-specific nuclease signal
      amplification.
AB  - MicroRNAs (miRNAs) play vital roles in physiologic and pathologic processes and
      are significant biomarkers for disease diagnostics and therapeutics. However,
      rapid, low-cost, sensitive, and selective detection of miRNAs remains a challenge
      because of their short length, sequence homology, and low abundance. Herein, we
      report for the first time that WS2 nanosheet can exhibit differential affinity
      toward short oligonucleotide fragment versus ssDNA probe and act as an efficient
      quencher for adsorbed fluorescent probes. This finding is utilized to develop a
      new strategy for simple, sensitive, and selective detection of miRNA by combining
      WS2 nanosheet based fluorescence quenching with duplex-specific nuclease signal
      amplification (DSNSA). This assay exhibits highly sensitive and selective with a
      detection limit of 300 fM and even discriminate single-base difference between
      the miRNA family members. The result indicates that this simple and cost
      effective strategy holds great potential application in biomedical research and
      clinical diagnostics. 

PMID- 24446759
TI  - Predicting health: the interplay between interpersonal communication and health
      campaigns.
AB  - The present study experimentally investigated the interplay between interpersonal
      communication and health message exposure in relation to alcohol consumption
      intentions. Participants were 174 students who took part in a study on the
      effects of an antialcohol message. At baseline, the authors assessed intention to
      refrain from binge drinking. At the second wave (2 weeks later), participants
      were assigned to the conditions of a 2 (antialcohol message or no-alcohol
      message) * 2 (alcohol conversation or control conversation) between-subjects
      design, after which intention was again assessed. Results showed that when
      participants talked about alcohol (instead of the control topic) and were not
      exposed to an antialcohol message, they were less inclined to refrain from binge
      drinking, an effect that was not visible when participants talked about alcohol
      after viewing an antialcohol message. These findings suggest that health campaign
      exposure moderates the influence of interpersonal communication on health
      variables. 

PMID- 24446760
TI  - Our recommendations for avoiding exposure to fungi outside the hospital for
      patients with haematological cancers.
AB  - Despite several chemotherapeutic and preventative advances, opportunistic fungal
      infections remain common unintended consequences of cancer treatment. Currently,
      cancer patients spend most of their time between treatments at home, where they
      can inadvertently come across potential hazards from environmental and food
      sources. Therefore, infection prevention measures are of the utmost importance
      for these patients. Although clinicians closely observe patients throughout their
      treatment courses in the hospital, the focus of clinical visits is predominantly
      on cancer care, and clinicians seldom provide recommendations for prevention of
      such infections. Herein, we provide practical recommendations for busy clinicians
      to help them educate patients regarding potential sources of fungal infections
      outside the hospital. 

PMID- 24446761
TI  - CYP2D6 genotyping and tamoxifen in the treatment of post-menopausal breast
      cancer.

PMID- 24446762
TI  - Dolutegravir: an exciting new kid on the block.
AB  - INTRODUCTION: Dolutegravir is the first second-generation integrase inhibitor
      approved for the treatment of naive as well as experienced HIV-infected
      individuals. AREAS COVERED: Data from pharmacokinetics, efficacy, safety,
      tolerability and resistance are reviewed from in vitro studies, Phase II and III
      clinical trials published in PubMed (Dolutegravir; S/GSK1349572) or presented in
      international meetings. EXPERT OPINION: Data from studies and clinical trials
      indicate that dolutegravir is safe, well tolerated and highly efficacious in the
      treatment of both antiretroviral-naive and treatment-experienced patients and
      appears to have a higher genetic barrier to resistance than first-generation
      integrase inhibitors.

PMID- 24446763
TI  - The secular growth acceleration: does it appear during fetal life?
AB  - OBJECTIVE: To test if secular growth acceleration occurs during fetal life.
      METHODS: ANOVA Kruskal-Wallis and Mann-Whitney U-test have been used for the
      biometric characteristics comparison of nowadays fetal population with those
      three decades ago and to test the hypothesis about the existence of secular
      growth acceleration during fetal life. For this purpose, we first calculated mean
      values of particular biometric parameters for the whole pregnancy. During the
      period 2002-2009 biparietal diameter, fetal length and abdominal circumference
      measurements in singleton uncomplicated pregnancies between 22 and 41 gestational
      weeks were obtained. Gestational age was estimated according to Naegele's rule
      and confirmed with an early ultrasound examination. Pregnancies with fetal
      cromosomopathies and malformations were excluded as well as those resulting in
      perinatal death. RESULTS: There were no statistically significant differences of
      the examined fetal biometric parameters measured by ultrasound between
      contemporary fetal population and those from 35 years ago. CONCLUSION: Our
      investigation did not undoubtedly prove that significant changes of fetal
      biometric parameters occurred in the last three decades. It is possible that
      secular growth acceleration does not exist in prenatal period but also the
      observed time period could have been short for this phenomenon to manifest.

PMID- 24446764
TI  - High-risk lead removal by planned sequential transvenous laser extraction and
      minimally invasive right thoracotomy.
AB  - INTRODUCTION: Transvenous pacemaker or implantable cardioverter defibrillator
      (ICD) lead extraction via mechanical or excimer laser sheath is typically safe
      and effective. Longer duration from implant, presence of large vegetations or
      thrombi, fractured leads, and prior failed extraction are risk factors predicting
      higher complication rates or incomplete or failed lead removal. Techniques
      developed for minimally invasive valve surgery were used in conjunction with
      laser extraction to refine a "hybrid" technique for lead extraction. We assessed
      the outcomes of high-risk lead extraction using this hybrid lead extraction
      technique. METHODS AND RESULTS: Retrospective assessment of clinical parameters
      and procedural outcomes in patients undergoing planned hybrid lead extraction
      from February 2008 to September 2012 was performed. We report 8 cases of hybrid
      lead extraction performed at our institution. We extracted 21 leads with average
      lead age of 13.8 years since implant. All leads were removed with complete
      clinical and radiographic success. There were no intraprocedure complications.
      One patient died of continued sepsis and 1 other had symptoms consistent with
      pulmonary embolism. CONCLUSIONS: Hybrid lead extraction using this technique is a
      safe and effective approach for removal of high-risk chronic pacemaker or ICD
      leads. This method extends the range of approachable leads resulting in complete
      removal without median sternotomy. Hybrid lead extraction can be scheduled
      electively facilitating complete lead removal with a low complication rate and
      short postoperative recovery time, mitigating the risks inherent in midline
      sternotomy or emergent cardiac surgical rescue.

PMID- 24446765
TI  - Platelet count and plateletcrit in Cavalier King Charles Spaniels and Greyhounds
      using the Advia 120 and 2120.
AB  - BACKGROUND: Models for the regulation of thrombopoiesis predict that platelet
      mass is the biologically regulated variable, yet clinical evaluations of
      thrombopoiesis are often based on platelet number. When thrombocytopenia and
      variation in platelet size occur concurrently, platelet count may poorly estimate
      total platelet mass, confounding clinical decision making. OBJECTIVE: We
      hypothesized that plateletcrit (PCT) provides clinically important information
      when platelet number is an incomplete representation of platelet mass, such as in
      genetic macrothrombocytopenia. METHODS: We retrospectively compared platelet
      count and PCTs with general reference intervals for 4 groups of dogs: sick
      Cavalier King Charles Spaniels (CKCS) and Greyhounds, presented for
      nonhematopoietic disease to the University of Minnesota (measured using an Advia
      2120) and Auburn University Teaching Hospitals (measured using an Advia 120) over
      a 3-year period. RESULTS: A canine PCT reference interval of 0.129-0.403% was
      established. None of the 4 sample groups had significantly more individuals below
      the reference interval for plateletcrit. For platelet count, only the 2 CKCS
      groups had significantly more individuals below the reference interval than
      predicted. CONCLUSION: Use of the PCT as determined by the Advia 120/2120
      appeared to avoid overestimation of low platelet mass in sick CKCS in a clinical
      setting. In contrast, the PCT performed similarly to the platelet count in
      evaluation of platelet mass in sick Greyhounds. Evaluation of the PCT should be
      considered in other conditions associated with increased mean platelet volume.

PMID- 24446766
TI  - Associations of oxidative stress status parameters with traditional
      cardiovascular disease risk factors in patients with schizophrenia.
AB  - BACKGROUND: The purpose of this study was to assess oxidative stress status
      parameters and their possible associations with traditional cardiovascular risk
      factors in patients with schizophrenia, as well as their potential for patient
      control discrimination. METHODS: Fasting glucose, lipid profile and oxidative
      stress status parameters were assessed in 30 schizophrenic patients with atypical
      antipsychotic therapy and 60 control subjects. RESULTS: Malondialdehyde (MDA),
      pro-oxidant/antioxidant balance (PAB) and total anti-oxidant status (TAS) were
      significantly higher whereas total sulfhydryl (SH) groups were significantly
      lower in schizophrenic patients vs. control group. Higher serum PAB values showed
      an independent association with schizophrenia. The addition of PAB to
      conventional risk factors improved discrimination between healthy control
      subjects and patients. CONCLUSION: Increased oxidative stress and changed lipid
      profile parameters are associated in schizophrenic patients and may indicate risk
      for atherosclerosis. The serum PAB level may reflect the levels of oxidative
      stress in schizophrenia and improve discrimination of patients from controls.

PMID- 24446767
TI  - Mechanistic insight into the spirocyclopropane isoxazolidine ring contraction.
AB  - A mechanistic study of the ring contraction of spirocyclopropane isoxazolidines
      to form beta-lactams is reported. Based on experimental and computational
      investigations, we propose a concerted mechanism that proceeds with retention of
      configuration during cyclopropane cleavage. 

PMID- 24446768
TI  - Toward metal complexes that can directionally walk along tracks: controlled
      stepping of a molecular biped with a palladium(II) foot.
AB  - We report on the design, synthesis, and operation of a bimetallic molecular biped
      on a three-foothold track. The "walker" features a palladium(II) complex "foot"
      that can be selectively stepped between 4-dimethylaminopyridine and pyridine
      ligand sites on the track via reversible protonation while the walker remains
      attached to the track throughout by means of a kinetically inert platinum(II)
      complex foot. The substitution pattern of the three ligand binding sites,
      together with the kinetic stability of the metal-ligand coordination bonds,
      affords the two positional isomers a high degree of metastability, meaning that
      altering the chemical state of the track does not automatically instigate
      stepping in the absence of an additional stimulus (heat in the presence of a
      coordinating solvent). The use of metastable metal complexes for foot-track
      interactions offers a promising alternative to dynamic covalent chemistry for the
      design of small-molecule synthetic molecular walkers. 

PMID- 24446769
TI  - Blueberry supplementation improves memory in middle-aged mice fed a high-fat
      diet.
AB  - Consuming a high-fat diet may result in behavioral deficits similar to those
      observed in aging animals. It has been demonstrated that blueberry
      supplementation can allay age-related behavioral deficits. To determine if
      supplementation of a high-fat diet with blueberries offers protection against
      putative high-fat diet-related declines, 9-month-old C57Bl/6 mice were maintained
      on low-fat (10% fat calories) or high-fat (60% fat calories) diets with and
      without 4% freeze-dried blueberry powder. Novel object recognition memory was
      impaired by the high-fat diet; after 4 months on the high-fat diet, mice spent
      50% of their time on the novel object in the testing trial, performing no greater
      than chance performance. Blueberry supplementation prevented recognition memory
      deficits after 4 months on the diets, as mice on this diet spent 67% of their
      time on the novel object. After 5 months on the diets, mice consuming the high
      fat diet passed through the platform location less often than mice on low-fat
      diets during probe trials on days 2 and 3 of Morris water maze testing, whereas
      mice consuming the high-fat blueberry diet passed through the platform location
      as often as mice on the low-fat diets. This study is a first step in determining
      if incorporating more nutrient-dense foods into a high-fat diet can allay
      cognitive dysfunction. 

PMID- 24446770
TI  - Genetic evidence and new morphometric data as essential tools to identify the
      Patagonian seahorse Hippocampus patagonicus (Pisces, Syngnathidae).
AB  - A genetic study to support morphometric analyses was used to improve the
      description and validate the Patagonian seahorse Hippocampus patagonicus
      (Syngnathidae) on the basis of a large number of specimens collected in the type
      locality (San Antonio Bay, Patagonia, Argentina). DNA sequence data (from the
      cytochrome b region of the mitochondrial genome) were used to differentiate this
      species from its relatives cited for the west Atlantic Ocean. Both phylogenetic
      and genetic distance analyses supported the hypothesis that H. patagonicus is a
      species clearly differentiated from others, in agreement with morphometric
      studies. Hippocampus patagonicus can be distinguished from Hippocampus erectus by
      the combination of the following morphometric characteristics: (1) in both sexes
      and all sizes of H. patagonicus, the snout length is always less than the
      postorbital length, whereas the snout length of H. erectus is not shorter than
      the postorbital length in the largest specimens; (2) in both sexes of H.
      patagonicus, the trunk length:total length (LTr :LT ) is lower than in H. erectus
      (in female H. patagonicus: 0.27-0.39, H. erectus: 0.36-0.40 and in male H.
      patagonicus: 0.24-0.34, H. erectus: 0.33-0.43) and (3) in both sexes, tail
      length:total length (LTa :LT ) in H. patagonicus is larger than in H. erectus
      (0.61-0.78 v. 0.54-0.64). 

PMID- 24446771
TI  - Selective DNA purine base photooxidation by bis-terdentate iridium(III)
      polypyridyl and cyclometalated complexes.
AB  - Two bis-terdentate iridium(III) complexes with polypyridyl and cyclometalated
      ligands have been prepared and characterized. Their spectroscopic and
      electrochemical properties have been studied, and a photophysical scheme
      addressing their properties is proposed. Different types of excited states have
      been considered to account for the deactivation processes in each complex.
      Interestingly, in the presence of mono- or polynucleotides, a photoinduced
      electron-transfer process from a DNA purine base (i.e., guanine or adenine) to
      the excited complex is shown through luminescence quenching experiments. For the
      first time, this work reports evidence for selective DNA purine bases oxidation
      by excited iridium(III) bis-terdentate complexes. 

PMID- 24446772
TI  - A coarse-grained model for epoxy molding compound.
AB  - We present a coarse-grained model for molecular dynamics simulations of an epoxy
      system composed of epoxy phenol novolac as epoxy monomer and bisphenol-A as the
      cross-linking agent. The epoxy and hardener molecules are represented as short
      chains of connected beads, and cross-linking is accomplished by introducing bonds
      between reactive beads. The interbead potential, composed of Lennard-Jones, bond
      stretching, and angle bending terms, is parametrized through an optimization
      process based on a particle swarm optimization method to fit certain key
      thermomechanical properties of the material obtained from experiments and
      previous full atomistic simulations. The newly developed coarse-grained model is
      capable of predicting a number of thermomechanical properties of the epoxy
      system. The predictions are in very good agreement with available data in the
      literature. More importantly, our coarse-grained model is capable of predicting
      tensile failure of the epoxy system, a capability that no other conventional
      molecular dynamic simulation model has. Finally, our coarse-grained model can
      speed up the simulations by more than an order of magnitude when compared with
      traditional molecular dynamic simulations. 

PMID- 24446773
TI  - Cognitive correlates of psychosis in patients with Parkinson's disease.
AB  - INTRODUCTION: Psychosis and hallucinations occur in 20-30% of patients with
      Parkinson's disease (PD). In the current study, we investigate cognitive
      functions in relation to the occurrence of psychosis in PD patients. METHODS: We
      tested three groups of subjects - PD with psychosis, PD without psychosis and
      healthy controls - on working memory, learning and transitive inference tasks,
      which are known to assess prefrontal, basal ganglia and hippocampal functions.
      RESULTS: In the working memory task, results show that patients with and without
      psychosis were more impaired than the healthy control group. In the transitive
      inference task, we did not find any difference among the groups in the learning
      phase performance. Importantly, PD patients with psychosis were more impaired
      than both PD patients without psychosis and controls at transitive inference. We
      also found that the severity of psychotic symptoms in PD patients [as measured by
      the Unified Parkinson Disease Rating Scale Thought Disorder (UPDRS TD) item] is
      directly associated with the severity of cognitive impairment [as measured by the
      mini-mental status exam (MMSE)], sleep disturbance [as measured by the Scales for
      Outcome in Parkinson Disease (SCOPA) sleep scale] and transitive inference
      (although the latter did not reach significance). CONCLUSIONS: Although
      hypothetical, our data may suggest that the hippocampus is a neural substrate
      underlying the occurrence of psychosis, sleep disturbance and cognitive
      impairment in PD patients.

PMID- 24446774
TI  - Near-infrared excited state dynamics of melanins: the effects of iron content,
      photo-damage, chemical oxidation, and aggregate size.
AB  - Ultrafast pump-probe measurements can discriminate the two forms of melanin found
      in biological tissue (eumelanin and pheomelanin), which may be useful for
      diagnosing and grading melanoma. However, recent work has shown that bound iron
      content changes eumelanin's pump-probe response, making it more similar to that
      of pheomelanin. Here we record the pump-probe response of these melanins at a
      wider range of wavelengths than previous work and show that with shorter pump
      wavelengths the response crosses over from being dominated by ground-state
      bleaching to being dominated by excited-state absorption. The crossover
      wavelength is different for each type of melanin. In our analysis, we found that
      the mechanism by which iron modifies eumelanin's pump-probe response cannot be
      attributed to Raman resonances or differences in melanin aggregation and is more
      likely caused by iron acting to broaden the unit spectra of individual
      chromophores in the heterogeneous melanin aggregate. We analyze the dependence on
      optical intensity, finding that iron-loaded eumelanin undergoes irreversible
      changes to the pump-probe response after intense laser exposure. Simultaneously
      acquired fluorescence data suggest that the previously reported "activation" of
      eumelanin fluorescence may be caused in part by the dissociation of metal ions or
      the selective degradation of iron-containing melanin. 

PMID- 24446778
TI  - Morphological and morphometric study of the androgenetic alopecic scalp using two
      and three-dimensional analysis comparing regional differences.
AB  - BACKGROUND: Androgenetic (male-type) alopecia (AGA) is caused by genetic and
      androgenetic effects. The progression of baldness results in smaller hair
      papillae, thinner hair and a shortened hair cycle. Alopecia occurs mainly in the
      frontal region and, to a lesser extent, in the occipital region. OBJECTIVES: The
      morphological differences in the hair follicular units between the alopecic
      frontal scalp and the vertex and occipital regions were compared using cross
      sectional histology and three-dimensional reconstruction. METHODS: Skin specimens
      were obtained from the frontal, vertex and occipital regions of 24 male human
      cadavers with fully progressed AGA, and from the frontal region of 32 normal
      cadaveric scalps. These specimens were fixed, processed using routine
      histological methods, serially sectioned at a thickness of 10 MUm and then
      stained with Masson's trichrome. The serial sections were reconstructed three
      dimensionally using 'Reconstruct' software. RESULTS: The ratios between the
      numbers of terminal and vellus hairs in the frontal and occipital regions in the
      AGA scalps were 0.2 : 1 and 3.5 : 1, respectively. Almost all of the hair
      follicles in the frontal region were vellus hair follicles. The sebaceous gland
      and arrector pili muscle were larger in the frontal region than in the occipital
      region. CONCLUSIONS: The morphology of the AGA scalp has been characterized. The
      terminal-to-vellus hair ratio in the occipital (normal) region was different from
      that in the frontal (alopecic) region. Moreover, sebaceous glands were larger in
      the frontal alopecic region than in the occipital region. These larger glands may
      be associated with other dermatological pathologies, such as seborrhoeic
      dermatitis.

PMID- 24446777
TI  - Systems toxicology: from basic research to risk assessment.
AB  - Systems Toxicology is the integration of classical toxicology with quantitative
      analysis of large networks of molecular and functional changes occurring across
      multiple levels of biological organization. Society demands increasingly close
      scrutiny of the potential health risks associated with exposure to chemicals
      present in our everyday life, leading to an increasing need for more predictive
      and accurate risk-assessment approaches. Developing such approaches requires a
      detailed mechanistic understanding of the ways in which xenobiotic substances
      perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology
      approaches offer modern strategies for gaining such mechanistic knowledge by
      combining advanced analytical and computational tools. Furthermore, Systems
      Toxicology is a means for the identification and application of biomarkers for
      improved safety assessments. In Systems Toxicology, quantitative systems-wide
      molecular changes in the context of an exposure are measured, and a causal chain
      of molecular events linking exposures with adverse outcomes (i.e., functional and
      apical end points) is deciphered. Mathematical models are then built to describe
      these processes in a quantitative manner. The integrated data analysis leads to
      the identification of how biological networks are perturbed by the exposure and
      enables the development of predictive mathematical models of toxicological
      processes. This perspective integrates current knowledge regarding bioanalytical
      approaches, computational analysis, and the potential for improved risk
      assessment.

PMID- 24446780
TI  - Near full-length genome identification of a novel HIV-1 recombinant form
      (CRF01_AE/B'/C) among heterosexuals in Jilin, China.
AB  - Recombinant forms contribute significantly to the genetic diversity of HIV-1.
      Here we report a novel HIV-1 recombinant form (CRF01_AE/B'/C) detected from a
      comprehensive HIV-1 molecular epidemiologic study among heterosexuals in Jilin
      province of northeastern China. Recombinant analyses of the near full-length
      genome (NFLG) of the novel HIV-1 recombinant isolate (JL.RF01) showed that the
      backbone of the genome was CRF01_AE, and three insertions of subtype B' (242,
      370, and 233 bp) and C (1142, 230, and 271 bp), respectively, were inserted along
      the genome. Phylogenetic analyses revealed that the novel HIV-1 recombinant form
      (CRF01_AE/B'/C) more likely originated from Thailand subtype B' and CRF01_AE and
      India subtype C. We report a unique mosaic structure that is distinct to HIV-1
      CRF01_AE/B'/C recombinant viruses reported to date. The emergence of this novel
      recombinant form (CRF01_AE/B'/C) suggests the increasing significance of
      heterosexual transmission contributing to the complexity of the HIV-1 epidemic in
      northeastern China.

PMID- 24446779
TI  - Comparison of tissue-engineered and artificial dermis grafts after removal of
      basal cell carcinoma on face--a pilot study.
AB  - BACKGROUND: Planning reconstruction for facial defects should include the safest
      and least-invasive methods, with a goal of achieving optimal functional and
      cosmetic outcomes. OBJECTIVE: To compare tissue-engineered dermis grafts with
      artificial dermis grafts after removal of basal cell carcinoma (BCC) on the face.
      MATERIALS AND METHODS: A tissue-engineered dermis composed of autologous cultured
      dermal fibroblasts seeded on a hyaluronic acid sheet was applied to 16 patients.
      Grafting of hyaluronic acid sheets that did not contain fibroblasts (artificial
      dermis group) was performed in 13 patients. Healing time, scar condition, and
      patient satisfaction were compared. RESULTS: The wounds of the tissue-engineered
      dermis group reepithelialized after 31.4 +/- 5.3 days and those of the artificial
      dermis group after 34.2 +/- 4.9 days. The tissue-engineered dermis graft was
      superior in scar quality. In particular, statistically significant differences
      were detected in the height and contracture of scars, although there were no
      significant differences in terms of scar texture or color match. Patient
      satisfaction in the tissue-engineered dermis graft group (8.3 +/- 1.0) was also
      statistically superior to that in the artificial dermis group (6.9 +/- 1.4).
      CONCLUSION: The tissue-engineered dermis graft is superior to the artificial
      dermis graft for covering defects after removal of BCC on the face.

PMID- 24446781
TI  - Hypertrophic cardiomyopathy with intermittent free mitral regurgitation-a
      surgical dilemma.
AB  - We describe the case of a 52-year-old woman presenting with non-ST elevation
      myocardial infarction, atrial fibrillation, and a new diagnosis of hypertrophic
      cardiomyopathy. Transesophageal echocardiography following hemodynamic
      deterioration revealed completely restricted mitral leaflet motion with free
      mitral regurgitation, and severe left ventricular outflow tract (LVOT)
      obstruction. Surgical intervention was considered; however, repeat imaging
      following a period of clinical stability revealed resolution of the findings
      suggesting a transient ischemic etiology. The case is supported by clinical and
      echocardiographic images with movie clips, and a discussion of the likely
      pathology in the context of the underlying condition. 

PMID- 24446784
TI  - "Old friends in new guise": exploiting privileged structures for scaffold re
      evolution/refining.
AB  - The attempts to increase novel drug productivity through creative discovery
      technologies have fallen short of producing the satisfactory results. For these
      reasons, evolved from the concept of drug repositioning, "privileged structure"
      guided scaffold re-evolution/refining is a primary strategy to identify
      structurally novel chemotypes by modifying the central core structure and the
      side-chain of the existing active compounds, or to exploit undescribed
      bioactivites by making full use of readily derivatized motifs with well
      established synthetic protocols. Herein, we review the basic tricks of exploiting
      privileged structures for scaffold re-evolution/refining. The power of this
      strategy is exemplified in the discovery of other new therapeutic applications by
      refining privileged structures in anti-viral agents. 

PMID- 24446785
TI  - Commenting on health: a framing analysis of user comments in response to health
      articles online.
AB  - Public health officials have continually urged journalists and other members of
      the news media to ease off health frames that focus on individuals and to instead
      promote broader societal frames. Although some scholarly research has reinforced
      these pleas, none has examined the interplay between frames of health news
      coverage and resulting public comments. The current online environment invites
      such an analysis, allowing news organizations to post articles online and the
      public to comment on those articles. Using a content analysis, this study reveals
      thematic frames in online health stories may drive down gain-oriented responses,
      while episodic frames may prompt the public to share more personal comments.
      Furthermore, the findings examine other textual factors--gain and loss frames and
      mobilizing information--that may be driving the volume and frames of user
      comments to health stories online.

PMID- 24446786
TI  - The natural killer-activating receptor, NKG2D, on CD3+CD8+ T cells plays a
      critical role in identifying and killing autologous myeloma cells.
AB  - BACKGROUND: The NKG2D receptor, one of the natural killer (NK) cell-activating
      receptors, is expressed on the surface of CD3+CD8+ T cells, gammadelta+ T cells,
      NK cells, NKT cells, and a few CD4+ T cells. We show, for the first time, a
      critical role for the NKG2D receptor on CD3+CD8+ T cells isolated from myeloma
      patients, in identifying and killing autologous myeloma cells isolated from the
      same patients' marrow. We also show that blocking NKG2D using anti-NKG2D reverses
      the cytotoxicity while blocking HLA-I using antibodies does not have the same
      effect, showing that the autologous cytotoxicity is NKG2D dependent and major
      histocompatibility complex (MHC)-I independent. We further confirmed the NKG2D
      specificity by small interfering RNA (siRNA) down regulation of NKG2D receptor.
      STUDY DESIGN AND METHODS: Using ex vivo expansion methods that enrich for
      NKG2D+CD3+CD8+ T cells, we investigated whether these ex vivo expanded
      NKG2D+CD3+CD8+ T cells would recognize and lyse autologous and allogeneic myeloma
      cells, independent of T-cell receptor or MHC-I expression. RESULTS: Myeloma cell
      lysis by the NKG2D+CD3+CD8+ T cells correlated with the amount of NKG2D ligand
      expression. With receptor-ligand interaction, interferon-gamma and tumor necrosis
      factor-alpha were released. Blocking the NKG2D receptor by using either
      monoclonal antibodies or siRNAs inhibited the receptor's function and prevented
      myeloma cell lysis. CONCLUSION: Clinical trials are ongoing to determine a
      correlation with the number and function of NKG2D+CD3+CD8+ T cells and clinical
      outcomes in transplanted myeloma patients, including lymphocyte recovery
      following transplant and overall survival.

PMID- 24446789
TI  - The electrophysiologist's new clothes and the cardiac MRI that told the truth.

PMID- 24446790
TI  - Changing fit and fat bias using an implicit retraining task.
AB  - OBJECTIVE: To change implicit and explicit bias so that active obese people are
      regarded as more fit and normal weight sedentary people as less fit. DESIGN:
      Study one created a questionnaire that measured perceptions of active obese
      persons and sedentary normal weight persons on fitness-related items. Study two
      used a modified visual probe task to retrain perceptions regarding active obese
      persons and sedentary normal weight persons. MAIN OUTCOME MEASURES: Self-reported
      explicit bias was measured with a questionnaire and implicit bias was measured
      with response times collected during a visual probe task. RESULTS: The
      questionnaire reliably measured 'fitness and fatness' perceptions. In study two,
      pairing images of active obese persons with positive activity-related words
      resulted in active obese persons being explicitly rated more fit; pairing images
      of normal weight sedentary persons with negative words associated with sedentary
      lifestyles increased endorsement of normal weight people as unfit. There were no
      changes in implicit bias. CONCLUSIONS: Bias regarding how body weight is thought
      of relative to fitness can be altered by pairing images of obese persons being
      active with words such as 'health' and 'fit'. This is evidence that
      representations of persons of all body weight should be used when promoting
      physical activity.

PMID- 24446791
TI  - Osseous metaplasia within a canine insulinoma.
AB  - An 11-year-old male castrated mixed-breed dog was presented for exercise
      intolerance, tetraparesis, and persistent hypoglycemia. Abdominal ultrasound
      examination revealed 2 nodules within the right limb of the pancreas. Cytology
      from one nodule was consistent with a carcinoma of neuroendocrine origin, with a
      primary differential diagnosis of insulinoma. Histologic evaluation and
      immunohistochemistry for synaptophysin and insulin confirmed the diagnosis of
      insulinoma. Additionally, there was a solitary nodule of mineralized compact bone
      composing approximately 60% of the mass. To the authors' knowledge, this is the
      first report of osseous metaplasia within an insulinoma (islet cell carcinoma). 

PMID- 24446792
TI  - CYP2D6 genotyping and tamoxifen in the treatment of post-menopausal breast cancer
      - a reply.

PMID- 24446793
TI  - Electrostatic spray ionization mass spectrometry imaging.
AB  - Imaging samples on a surface by mass spectrometry (MS) requires the combination
      of MS detection with a scanning mode that enables localized desorption and
      ionization and/or detection of sample analytes with good spatial resolution. We
      have developed a new mass spectrometry imaging (MSI) method based on
      electrostatic spray ionization. It works under ambient conditions and can be
      applied to a wide range of molecules providing quantitative MS analysis even in
      the presence of salts in excess. 2D MS images of protein and peptide spots,
      inkjet-printed black dye patterns, and cells were obtained. The presented novel
      ambient ionization mass spectrometry imaging method can find many applications in
      analytical and bioanalytical chemistry. 

PMID- 24446794
TI  - Stachybotrys eucylindrospora isolated from foreign material following a traumatic
      eye injury.
AB  - Stachybotrys eucylindrospora was characterised as a new species in 2007, and we
      present the first report of this organism isolated from foreign material
      recovered from a patient. It is probable that isolates of this species have been
      previously identified as either Stachybotrys chartarum or Stachybotrys
      cylindrospora. 

PMID- 24446795
TI  - Linguistic and pragmatic aspects of narration in Finnish typically developing
      children and children with specific language impairment.
AB  - This study investigates narratives of Finnish children with specific language
      impairment (SLI) from linguistic and pragmatic perspectives, in order to get a
      comprehensive overview of these children's narrative abilities. Nineteen children
      with SLI (mean age 6;1 years) and 19 typically developing age-matched children
      participated in the study. Their picture-elicited narrations were analysed for
      linguistic productivity and complexity, grammatical and referential accuracy,
      event content, the use of mental state expressions and narrative comprehension.
      Children with SLI showed difficulties in every aspect of narration in comparison
      to their peers. Only one measure of productivity, the number of communication
      units, did not reach statistical significance. Not only was linguistic structure
      fragile but also pragmatic aspects of storytelling (referencing, event content,
      mental state expressions and inferencing) were demanding for children with SLI.
      Results suggest that pragmatic aspects of narration should be taken into account
      more often when assessing narrative abilities of children with SLI.

PMID- 24446796
TI  - Consonant acquisition in the Malay language: a cross-sectional study of preschool
      aged Malay children.
AB  - To date, there has been little research done on phonological acquisition in the
      Malay language of typically developing Malay-speaking children. This study serves
      to fill this gap by providing a systematic description of Malay consonant
      acquisition in a large cohort of preschool-aged children between 4- and 6-years
      old. In the study, 326 Malay-dominant speaking children were assessed using a
      picture naming task that elicited 53 single words containing all the primary
      consonants in Malay. Two main analyses were conducted to study their consonant
      acquisition: (1) age of customary and mastery production of consonants; and (2)
      consonant accuracy. Results revealed that Malay children acquired all the
      syllable-initial and syllable-final consonants before 4;06-years-old, with the
      exception of syllable-final /s/, /h/ and /l/ which were acquired after 5;06-years
      old. The development of Malay consonants increased gradually from 4- to 6 years
      old, with female children performing better than male children. The accuracy of
      consonants based on manner of articulation showed that glides, affricates,
      nasals, and stops were higher than fricatives and liquids. In general, syllable
      initial consonants were more accurate than syllable-final consonants while
      consonants in monosyllabic and disyllabic words were more accurate than
      polysyllabic words. These findings will provide significant information for
      speech-language pathologists for assessing Malay-speaking children and designing
      treatment objectives that reflect the course of phonological development in
      Malay.

PMID- 24446797
TI  - Voice onset time and speakers' age: data from Hungarian.
AB  - The aim of this paper was to investigate the VOT of voiceless plosives (/p, t,
      k/) in the speech of Hungarian-speaking elderly. Read speech of 25 old (70 to 90
      years) and 25 young (21 to 32 years) was analyzed. In each recording, the VOT of
      phonologically short [p, t, k] was measured. Our data show that VOT values of all
      three types of voiceless plosives would exhibit significant differences both in
      old and in young Hungarians' speech. Bilabial and alveolar plosives had
      significantly longer VOT in old subjects' speech than in that of young subjects,
      while old subjects produced significantly shorter VOTs in pronouncing [k] than
      their younger peers. We argue that these results are attributable to (1)
      significantly slower rate of articulation (yielding longer speech sounds in
      general), and (2) the articulatory and aerodynamic background of the production
      of plosives.

PMID- 24446798
TI  - Conversational topics in transsexual persons.
AB  - Abstract In general, speech language therapy for transsexual persons focuses on
      pitch and pitch variation and more recently also on resonance. Other
      communicative aspects are dealt with far less often, especially language. This
      study investigated to what extent conversational topics might need attention in
      therapy for transsexual persons. A total of 111 males, 116 females, 28 male-to
      female and 18 female-to-male transsexuals were asked to indicate on a list with
      34 topics how often they speak about each topic (never, sometimes, often) in
      conversations with males, with females and in a gender mixed group. Results
      showed that transsexual persons behave in accordance with the desired gender.
      However, they also tend to adopt a position depending on the gender of their
      conversational partner. It can be concluded that in general it is not necessary
      to pay attention to conversational topics in therapy for transsexual persons. 

PMID- 24446799
TI  - Changes in voice onset time and motor speech skills in children following motor
      speech therapy: Evidence from /pa/ productions.
AB  - This study evaluated changes in motor speech control and inter-gestural
      coordination for children with speech sound disorders (SSD) subsequent to Prompts
      for Restructuring Oral and Muscular Phonetic Targets (PROMPT) intervention. We
      measured the distribution patterns of voice onset time (VOT) for a voiceless stop
      (/p/) to examine the changes in inter-gestural coordination. Two standardized
      tests were used (Verbal Motor Production Assessment for Children (VMPAC), GFTA-2)
      to assess the changes in motor speech skills and articulation. Data showed
      positive changes in patterns of VOT with a lower pattern of variability. All
      children showed significantly higher scores for VMPAC, but only some children
      showed higher scores for GFTA-2. Results suggest that the proprioceptive feedback
      provided through PROMPT had a positive influence on speech motor control and
      inter-gestural coordination in voicing behavior. This set of VOT data for
      children with SSD adds to our understanding of the speech characteristics
      underlying speech motor control. Directions for future studies are discussed.

PMID- 24446800
TI  - Modelling convection-enhanced delivery in normal and oedematous brain.
AB  - Convection-enhanced delivery (CED) could have clinical applications in the
      delivery of neuroprotective agents in brain injury states, such as ischaemic
      stroke. For CED to be safe and effective, a physician must have accurate
      knowledge of how concentration distributions will be affected by catheter
      location, flow rate and other similar parameters. In most clinical applications
      of CED, brain microstructures will be altered by pathological injury processes.
      Ischaemic stroke and other acute brain injury states are complicated by formation
      of cytotoxic oedema, in which cellular swelling decreases the fractional volume
      of the extracellular space (ECS). Such changes would be expected to significantly
      alter the distribution of neuroprotective agents delivered by CED. Quantitative
      characterization of these changes will help confirm this prediction and assist in
      efforts to model the distribution of therapeutic agents. Three-dimensional
      computational models based on a Nodal Point Integration (NPI) scheme were
      developed to model infusions in normal brain and brain with cytotoxic oedema.
      These models were compared to experimental data in which CED was studied in
      normal brain and in a middle cerebral artery (MCA) occlusion model of cytotoxic
      oedema. The computational models predicted concentration distributions with
      reasonable accuracy.

PMID- 24446801
TI  - The effect of probe placement on inter-trial variability when using the Cutometer
      MPA 580.
AB  - There is limited data independently assessing the optimal use of the Cutometer
      MPA580. The purpose of this study is to test the hypothesis that the assessment
      of elastic recoil is significantly different when utilizing two different probe
      placement protocols. In protocol A, four trials were performed, in which the
      probe was removed from the skin between trials. In protocol B, the probe was not
      removed from the skin between trials. Fifty-four patients were enrolled and all
      completed the testing. When assessing elasticity (Ua/Uf), the inter-class
      correlation was 0.83 for protocol A and 0.48 for protocol B (p <0.001). There was
      no significant difference between individual trials for protocol A. Trial one of
      protocol B was significantly different (p < 0.001) than trials 2-4 for protocol
      B. Trial one of protocol B was not significantly different than any trial in
      protocol A. The results of this study suggest that the method in which a
      clinician performs repeated measure testing has a significant effect on the
      outcome measures when using the Cutometer. Removing the probe between trials
      appears to result in measures with higher reliability.

PMID- 24446802
TI  - Handheld real-time volumetric imaging of the spine: technology development.
AB  - Technical difficulties, poor image quality and reliance on pattern
      identifications represent some of the drawbacks of two-dimensional ultrasound
      imaging of spinal bone anatomy. To overcome these limitations, this study sought
      to develop real-time volumetric imaging of the spine using a portable handheld
      device. The device measured 19.2 cm * 9.2 cm * 9.0 cm and imaged at 5 MHz centre
      frequency. 2D imaging under conventional ultrasound and volumetric (3D) imaging
      in real time was achieved and verified by inspection using a custom spine
      phantom. Further device performance was assessed and revealed a 75-min battery
      life and an average frame rate of 17.7 Hz in volumetric imaging mode. The results
      suggest that real-time volumetric imaging of the spine is a feasible technique
      for more intuitive visualization of the spine. These results may have important
      ramifications for a large array of neuraxial procedures.

PMID- 24446804
TI  - Rapid identification of cholinesterase inhibitors from the seedcases of
      mangosteen using an enzyme affinity assay.
AB  - Enzyme binding affinity has been recently introduced as a selective screening
      method to identify bioactive substances within complex mixtures. We used an assay
      which identified small molecule binders of acetylcholinesterase (AChE) using the
      following series of steps: incubation of enzyme with extract; centrifugation and
      filtration; identification of small molecule content in the flow through. The
      crude extract contained 10 peaks in the UPLC chromatogram. However, after
      incubation the enzyme, six peaks were reduced, indicating these compounds bound
      AChE. All these isolated compounds (2, 3, and 5-8) significantly inhibited human
      AChE with IC50s = 5.4-15.0 MUM and butyrylcholinsterase (IC50s = 0.7-11.0 MUM).
      All compounds exhibited reversible mixed kinetics. Consistent with the binding
      screen and fluorescence quenching, gamma-mangostin 6 had a much higher affinity
      for AChE than 9-hydroxycalabaxanthone 9. This validates this screening protocol
      as a rapid method to identify inhibitors of AChE.

PMID- 24446805
TI  - Characterization of the lipid fraction of wild sea urchin from the Sardinian Sea
      (western Mediterranean).
AB  - The fatty acid (FA) composition of Spatangus purpureus, Echinus melo,
      Sphaerechinus granularis, and Paracentrotus lividus, sea urchins, has been
      studied. Sea urchins were collected at different depth along Sardinia coast in
      the Mediterranean sea, and their gonad was measured, separated, and analyzed for
      FA composition by gas chromatography-mass spectrometry. A total of 53 FAs were
      detected, 16 saturated (SFA), 10 monounsaturated (MUFA), 9 polyunsaturated
      (PUFA), and 13 highly unsaturated (HUFA). Moreover, 5 furan FAs (FFAs) were
      revealed for the first time in sea urchin. The HUFA and PUFA classes were the
      most represented accounting for almost 80% of total FAs. Among these compounds,
      C20:4 n6 (19.64, 20.52, 23.37, and 8.48 mg/g, respectively) and C22:6 n3 (19.68,
      20.05, 3.83, and 1.78 mg/g, respectively) were the most abundant. The results of
      principal component analysis indicated that the sea urchin samples could be
      clearly discriminated with respect to their FAs composition. 

PMID- 24446806
TI  - Two dimensional molecular electronics spectroscopy for molecular fingerprinting,
      DNA sequencing, and cancerous DNA recognition.
AB  - Laser-driven molecular spectroscopy of low spatial resolution is widely used,
      while electronic current-driven molecular spectroscopy of atomic scale resolution
      has been limited because currents provide only minimal information. However,
      electron transmission of a graphene nanoribbon on which a molecule is adsorbed
      shows molecular fingerprints of Fano resonances, i.e., characteristic features of
      frontier orbitals and conformations of physisorbed molecules. Utilizing these
      resonance profiles, here we demonstrate two-dimensional molecular electronics
      spectroscopy (2D MES). The differential conductance with respect to bias and gate
      voltages not only distinguishes different types of nucleobases for DNA sequencing
      but also recognizes methylated nucleobases which could be related to cancerous
      cell growth. This 2D MES could open an exciting field to recognize single
      molecule signatures at atomic resolution. The advantages of the 2D MES over the
      one-dimensional (1D) current analysis can be comparable to those of 2D NMR over
      1D NMR analysis. 

PMID- 24446807
TI  - TMSCN/DBU-mediated facile redox transformation of alpha,beta-unsaturated
      aldehydes to carboxylic acid derivatives.
AB  - Redox transformation of an alpha,beta-unsaturated aldehyde to a carboxylic acid
      derivative by means of a combination of TMSCN and DBU was investigated. In
      addition to the wide use of the carboxylic acid derivatives provided by this
      reaction, temperature-dependent control of the kinetic or thermodynamic
      protonation pattern was found to selectively switch the stereochemistry of the
      acyl group in the product. 

PMID- 24446808
TI  - Epitaxial self-assembly of binary molecular components into branched nanowire
      heterostructures for photonic applications.
AB  - We report a sequential epitaxial growth to prepare organic branched nanowire
      heterostructures (BNwHs) consisting of a microribbon trunk of 1,4-dimethoxy-2,5
      di[4'-(cyano)styryl]benzene (COPV) with multiple nanowire branches of 2,4,5
      triphenylimidazole (TPI) in a one-pot solution synthesis. The synthesis involves
      a seeded-growth process, where COPV microribbons are grown first as a trunk
      followed by a seeded-growth of TPI nanowire branches at the pregrown trunk
      surfaces. Selected area electron diffraction characterizations reveal that
      multiple hydrogen-bonding interactions between TPI and COPV components play an
      essential role in the epitaxial growth as a result of the structural matching
      between COPV and TPI crystals. A multichannel optical router was successfully
      realized on the basis of the passive waveguides of COPV green photoluminescence
      (PL) along TPI nanowire branches in a single organic BNwH. 

PMID- 24446809
TI  - Ab initio studies on the photophysics of uric acid and its monohydrates: role of
      the water molecule.
AB  - The photophysical behavior of three lowest-energy tautomers of uric acid and
      seven most stable isomers of uric acid monohydrate is comprehensively studied by
      ab initio calculations. Ground-state energies are calculated with the CCSD(T)
      method, while excitation and ionization energies as well as excited-state
      potential energy profiles of photoinduced processes are calculated with the CC2
      method. For the (1)pipi* state, it is found that the excitation energy of the
      monohydrate cluster is significantly lower than that of isolated uric acid when
      the water molecule is hydrogen-bonded at a specific carbonyl group. The
      calculated excited-state potential energy profiles suggest that some monohydrate
      isomers can undergo a migration of the water molecule from one site to another
      site in the (1)pipi* state with a small energy barrier. It is also found for both
      uric acid and its monohydrate that nonradiative decay via the NH bond
      dissociation in the (1)pisigma* state is likely to occur at higher excitation
      energies. On the basis of the computational results, possible mechanisms for the
      absence of specific isomers of uric acid monohydrate from the resonant two-photon
      ionization spectrum are discussed. 

PMID- 24446810
TI  - Delivery of polysaccharides using polymer particles: implications on size
      dependent immunogenicity, opsonophagocytosis, and protective immunity.
AB  - Bacterial capsular polysaccharides are components of many modern vaccines, but
      they are weakly immunogenic. Herein, we describe the delivery of pneumococcal
      capsular polysaccharide serotype-1 (PCP-1) in polylactide polymeric particles to
      enhance its immunogenicity. Immunization with PCP-1-entrapped particles elicited
      long-term memory antibody responses from a single intramuscular injection. PCP-1
      entrapped nanoparticles (NPs) elicited significantly higher anti-PCP-1 IgG
      responses than that observed with soluble and microparticles (MPs) formulations.
      Delivering PCP-1 and pneumococcal proteins in same particles did not improve the
      IgG response. The sera of animals immunized with PCP-1-entrapped particles
      promoted efficient opsonophagocytosis of pneumococci by macrophages. Single-dose
      immunization with PCP-1-entrapped particles conferred a long-term serotype
      specific protection against lethal pneumococcal challenge. The higher
      immunogenicity of PCP-1 nanoparticles showed correlation with enhanced uptake by
      antigen-presenting cells. The results highlight the potential of polymeric
      nanoparticles as an efficient means of presenting polysaccharide antigens to the
      immune system. 

PMID- 24446812
TI  - Correction to Synthesis of 2-N/S/C-substituted Benzothiazoles via Intramolecular
      Cyclative Cleavage of Benzotriazole Ring.

PMID- 24446811
TI  - Combined vestibular mucosal advancement and island pedicle flaps for the repair
      of a defect involving the cutaneous and vermilion upper lip.

PMID- 24446813
TI  - Sea-blue histiocytes in the bone marrow of a boy with severe congenital
      neutropenia associated with G6PC3 mutation.

PMID- 24446814
TI  - Public estimates of cancer frequency: cancer incidence perceptions mirror
      distorted media depictions.
AB  - Compared with incidence rates, certain cancers are over- or underrepresented in
      news coverage. Past content analytic research has consistently documented these
      news distortions, but no study has examined whether they are related to public
      perception of cancer incidence. Adults (N = 400) completed a survey with
      questions about perceived cancer incidence, news consumption, and attention to
      health news. Cancer incidence perceptions paralleled previously documented news
      distortions. Overrepresented cancers were overestimated (e.g., blood, head/brain)
      and underrepresented cancers were underestimated (e.g., male reproductive,
      lymphatic, thyroid, and bladder). Self-reported news consumption was related to
      perceptual distortions such that heavier consumers were more likely to
      demonstrate distorted perceptions of four cancers (bladder, blood, breast, and
      kidney). Distortions in risk perception and news coverage also mirrored
      discrepancies in federal funding for cancer research. Health care professionals,
      journalists, and the public should be educated about these distortions to reduce
      or mitigate potential negative effects on health behavior and decision making. 

PMID- 24446816
TI  - Synthesis, crystal and electronic structure of the quaternary magnetic EuTAl4Si2
      (T = Rh and Ir) compounds.
AB  - Single crystals of the quaternary europium compounds EuRhAl4Si2 and EuIrAl4Si2
      were synthesized by using the Al-Si binary eutectic as a flux. The structure of
      the two quaternary compounds has been refined by single crystal X-ray
      diffraction. Both compounds are stoichiometric and adopt an ordered derivative of
      the ternary KCu4S3 structure type (tetragonal tP8, P4/mmm). The two compounds
      reported here represent the first example of a quaternary and truly
      stoichiometric 1:1:4:2 phase crystallizing with this structure type. In light of
      our present results, the structure of the BaMg4Si3 compound given in literature
      as representing a new prototype is actually isotypic with the KCu4S3 structure.
      Local spin density approximation including the Hubbard U parameter (LSDA + U)
      calculations show that Eu ions are in the divalent state, with a significant
      hybridization between the Eu 5d, Rh (Ir) 4d (5d), Si 3p and Al 3p states.
      Magnetic susceptibility measured along the [001] direction confirms the divalent
      nature of the Eu ions in EuRhAl4Si2 and EuIrAl4Si2, which order magnetically near
      ~11 and ~15 K, respectively. 

PMID- 24446817
TI  - Measures of stored red blood cell quality.
AB  - Blood banking underpins modern medical care, but blood storage, necessary for
      testing and inventory management, reduces the safety and efficacy of individual
      units of red blood cells (RBCs). Stored RBCs are damaged by the accumulation of
      their own waste products, by enzymatic and oxidative injury, and by metabolically
      programmed cell death. These chemical activities lead to a complex RBC storage
      lesion that includes haemolysis, reduced in vivo recovery, energy and membrane
      loss, altered oxygen release, reduced adenosine tri-phosphate and nitric oxide
      secretion, and shedding of toxic products. These toxic products include
      lysophospholipids that can cause transfusion-related acute lung injury, free iron
      that can potentiate infections and cause inflammation, and shed microvesicles
      that can scavenge nitric oxide and potentiate inflammation and thrombosis.
      However, most of the obvious negative outcomes of RBC storage are uncommon and
      appear to be related to exceptionally bad units. Generally, the quality of stored
      RBCs is highly related to the conditions of storage, so refrigerator temperature,
      intact bags, residual leucocyte counts and visible haemolysis remain excellent
      general measures. Specific biochemical measures, such as adenosine 5'
      triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) concentrations, calcium and
      potassium content or lipid breakdown products, require specialized measures that
      are not widely available, involve destructive testing and generally reflect only
      a part of the storage lesion. This review describes a number of components of the
      storage lesion and their measurement and attempts to access the utility of the
      measures. 

PMID- 24446821
TI  - Increases in heart rate and serum cortisol concentrations in healthy dogs are
      positively correlated with an indoor waiting-room environment.
AB  - BACKGROUND: Few studies have investigated the effect of veterinary clinical
      procedures on the welfare of dogs, with specific emphasis on the veterinary
      practice environment. Clinicopathologic variables have also not been assessed in
      these potentially stressful situations. Similar to human clinical studies, the
      veterinary clinical waiting room could present a significant stress factor for
      dogs. OBJECTIVES: The present study was designed to investigate the effect of
      waiting-room environment on serum cortisol and glucose alterations as well as
      heart rate in privately owned healthy dogs. METHODS: The clinical trial included
      24 healthy dogs that were divided into 2 groups: the clinical waiting-room group
      (A) and the control group (B) that waited outside in a garden. During the entire
      experiment, 18 dogs (9 dogs per group) were monitored with a human heart rate
      monitor fastened around the chest. After 20 minutes of waiting, blood samples
      were collected from all of the dogs (24 dogs) to determine serum cortisol
      concentration. RESULTS: Serum cortisol concentration and mean, maximum, and
      minimum heart rate were significantly higher in group A compared with group B,
      but there was no statistical difference in serum glucose concentrations between
      the 2 study groups. CONCLUSIONS: Results of this study suggest that the waiting
      room is a potentially stressful situation for dogs in clinical veterinary
      practice, when compared with a garden, based on the assessment of adrenal cortex
      function and heart rate evaluation.

PMID- 24446820
TI  - Outcome evaluation results of school-based cybersafety promotion and
      cyberbullying prevention intervention for middle school students.
AB  - Guided largely by the Extended Parallel Process Model, the Arizona Attorney
      General's Social Networking Safety Promotion and Cyberbullying Prevention
      presentation attempts to shape, change, and reinforce middle school students'
      perceptions, attitudes, and intentions related to these important social issues.
      This study evaluated the short-term effects of this presentation in a field
      experiment using a posttest-only control-group design with random assignment to
      conditions. A total of 425 sixth, seventh, and eighth graders at a public middle
      school in a large Southwestern city participated in this study. Results reveal
      several interesting trends across grade levels regarding cyberbullying
      perpetration and victimization, and concerning access to various communication
      technologies. The intervention had the hypothesized main effect on eight of the
      dependent variables under investigation. Examination of condition by grade
      interaction effects offered further support for an additional four hypotheses
      (i.e., the intervention positively affected or reversed a negative trend on four
      dependent variables in at least one grade). Ideas and implications for future
      social networking safety promotion and cyberbullying prevention interventions are
      discussed.

PMID- 24446822
TI  - Infrarenal origin of the superior mesenteric artery challenges the procurement
      surgeon.

PMID- 24446824
TI  - Pulmonary vein in pathogenesis of persistent atrial fibrillation: an unsettled
      controversy.

PMID- 24446823
TI  - A predictive processing theory of sensorimotor contingencies: Explaining the
      puzzle of perceptual presence and its absence in synesthesia.
AB  - Normal perception involves experiencing objects within perceptual scenes as real,
      as existing in the world. This property of "perceptual presence" has motivated
      "sensorimotor theories" which understand perception to involve the mastery of
      sensorimotor contingencies. However, the mechanistic basis of sensorimotor
      contingencies and their mastery has remained unclear. Sensorimotor theory also
      struggles to explain instances of perception, such as synesthesia, that appear to
      lack perceptual presence and for which relevant sensorimotor contingencies are
      difficult to identify. On alternative "predictive processing" theories,
      perceptual content emerges from probabilistic inference on the external causes of
      sensory signals, however, this view has addressed neither the problem of
      perceptual presence nor synesthesia. Here, I describe a theory of predictive
      perception of sensorimotor contingencies which (1) accounts for perceptual
      presence in normal perception, as well as its absence in synesthesia, and (2)
      operationalizes the notion of sensorimotor contingencies and their mastery. The
      core idea is that generative models underlying perception incorporate explicitly
      counterfactual elements related to how sensory inputs would change on the basis
      of a broad repertoire of possible actions, even if those actions are not
      performed. These "counterfactually-rich" generative models encode sensorimotor
      contingencies related to repertoires of sensorimotor dependencies, with
      counterfactual richness determining the degree of perceptual presence associated
      with a stimulus. While the generative models underlying normal perception are
      typically counterfactually rich (reflecting a large repertoire of possible
      sensorimotor dependencies), those underlying synesthetic concurrents are
      hypothesized to be counterfactually poor. In addition to accounting for the
      phenomenology of synesthesia, the theory naturally accommodates phenomenological
      differences between a range of experiential states including dreaming,
      hallucination, and the like. It may also lead to a new view of the
      (in)determinacy of normal perception.

PMID- 24446825
TI  - Effect of risk information exposure on consumers' responses to foods with insect
      contamination.
AB  - This study explores the impact that scientific information about insect
      contamination of food has on consumer perceptions. Participants (n = 320,
      Japanese consumers) were randomly assigned to 1 of 8 information-type conditions:
      (1) information about insect type, (2) information about contamination processes,
      (3) information about the safety of contaminated food, (4, 5, 6) combinations of
      2 of (1), (2), and (3) above, (7) all information, and (8) no-information, and
      asked to rate their valuation, behavioral intention, and attitude toward food
      with insect contamination. Results demonstrated that some combinations of
      scientific information that include the safety of the contaminated food are
      effective to reduce consumers' compulsive rejection of insect contamination in
      food, whereas the single presentation of information about insect type increases
      consumers' explicit rejection of both the contaminated product and the
      manufacturer. These findings have implications for the coordination of risk
      communication strategies. 

PMID- 24446827
TI  - Non-receptor protein tyrosine kinases signaling pathways in normal and cancer
      cells.
AB  - Protein tyrosine kinases (PTKs) are enzymes that transfer phosphate groups to
      tyrosine residues on protein substrates. Phosphorylation of proteins causes
      changes in their function and/or enzymatic activity resulting in specific
      biological responses. There are two classes of PTKs: the transmembrane receptor
      PTKs and the cytoplasmic non-receptor PTKs (NRTKs). NRTKs are involved in
      transduction of signals originating from extracellular clues, which often
      interact with transmembrane receptors. Thus, they are important components of
      signaling pathways which regulate fundamental cellular functions such as cell
      differentiation, apoptosis, survival, and proliferation. The activity of NRTKs is
      tightly regulated, and de-regulation and/or overexpression of NRTKs has been
      implicated in malignant transformation and carcinogenesis. Research on NRTKs has
      shed light on the mechanisms of a number of cellular processes including those
      involved in carcinogenesis. Not surprisingly, several tyrosine kinase inhibitors
      are in use as treatment for a number of malignancies, and more are under
      investigation. This review deals with the structure, function, and signaling
      pathways of nine main families of NRTKs in normal and cancer cells.

PMID- 24446826
TI  - High temperature SELMA: evolution of DNA-supported oligomannose clusters which
      are tightly recognized by HIV bnAb 2G12.
AB  - SELMA (SELection with Modified Aptamers) is a directed evolution method which can
      be used to develop DNA-supported clusters of carbohydrates in which the geometry
      of clustering is optimized for strong recognition by a lectin of interest.
      Herein, we report a modification of SELMA which results in glycoclusters which
      achieve dramatically stronger target recognition (100-fold) with dramatically
      fewer glycans (2-3-fold). Our first applications of SELMA yielded clusters of 5
      10 oligomannose glycans which were recognized by broadly neutralizing HIV
      antibody 2G12 with moderate affinities (150-500 nM Kd's). In the present
      manuscript, we report glycoclusters containing just 3-4 glycans, which are
      recognized by 2G12 with Kd's as low as 1.7 nM. These glycoclusters are recognized
      by 2G12 as tightly as is the HIV envelope protein gp120, and they are the first
      constructs to achieve this tight recognition with the minimal number of Man9
      units (3-4) necessary to occupy the binding sites on 2G12. They are thus of great
      interest as immunogens which might elicit broadly neutralizing antibodies against
      HIV. 

PMID- 24446828
TI  - Knockdown of E2F2 inhibits tumorigenicity, but preserves stemness of human
      embryonic stem cells.
AB  - Tumorigenicity of human pluripotent stem cells is a major threat limiting their
      application in cell therapy protocols. It remains unclear, however, whether
      suppression of tumorigenic potential can be achieved without critically affecting
      pluripotency. A previous study has identified hyperexpressed genes in cancer stem
      cells, among which is E2F2, a gene involved in malignant transformation and stem
      cell self-renewal. Here we tested whether E2F2 knockdown would affect the
      proliferative capacity and tumorigenicity of human embryonic stem cells (hESC).
      Transient E2F2 silencing in hESC significantly inhibited expression of the proto
      oncogenes BMI1 and HMGA1, in addition to proliferation of hESC, indicated by a
      higher proportion of cells in G1, fewer cells in G2/M phase, and a reduced
      capacity to generate hESC colonies in vitro. Nonetheless, E2F2-silenced cells
      kept expression of typical pluripotency markers and displayed differentiation
      capacity in vitro. More importantly, E2F2 knockdown in hESC significantly
      inhibited tumor growth in vivo, which was considerably smaller than tumors
      generated from control hESC, although displaying typical teratoma traits, a major
      indicator of pluripotency retention in E2F2-silenced cells. These results suggest
      that E2F2 knockdown can inhibit hESC proliferation and tumorigenicity without
      significantly harming stemness, providing a rationale to future protocols aiming
      at minimizing risks related to therapeutic application of cells and/or products
      derived from human pluripotent cells. 

PMID- 24446829
TI  - A physiologically based modeling strategy during preclinical CNS drug
      development.
AB  - Physiologically based pharmacokinetic (PBPK) modeling of the central nervous
      system (CNS) provides the opportunity to predict the relevant drug concentrations
      at the therapeutic target site during preclinical and clinical development. In
      order to successfully interpret model results, and to provide confidence in the
      subsequent human predictions, it is essential that an appropriate model structure
      is chosen at the preclinical stage which takes into account both physiological
      and drug-specific knowledge. However, the models published to date in the
      literature show significant variation in the approaches applied by different
      authors, which can lead to difficulties in the interpretation of model parameter
      estimates. We aimed to develop a coherent PBPK modeling approach in the rat,
      which would also be adaptable depending on the quantity and quality of in vivo
      data obtained during drug development. Based on a sensitivity analysis of the
      model parameters, and using three CNS drugs as case studies (atomoxetine,
      acetaminophen, and S 18986), we proposed a decision tree to aid in the
      appropriate parametrization and structure of the model according to the data
      available. We compared our parameter estimates to those originally published, and
      considered the impact of the respective approaches on the mechanistic
      interpretation of the parameter values. Since the measurement of brain
      extracellular fluid (ECF) concentrations using microdialysis is not routinely
      performed in the industrial environment, we also evaluated the bottom-up scaling
      of in vitro permeability data from the Caco-2 cell line to predict BBB passive
      permeability in the absence of measured ECF concentrations. Our strategy
      demonstrates the value of PBPK as a prediction tool throughout the development
      process of CNS-targeting drugs. 

PMID- 24446830
TI  - The onset of depression during the great recession: foreclosure and older adult
      mental health.
AB  - OBJECTIVES: We examined neighborhood-level foreclosure rates and their
      association with onset of depressive symptoms in older adults. METHODS: We linked
      data from the National Social Life, Health, and Aging Project (2005-2006 and 2010
      2011 waves), a longitudinal, nationally representative survey, to data on zip
      code-level foreclosure rates, and predicted the onset of depressive symptoms
      using logit-linked regression. RESULTS: Multiple stages of the foreclosure
      process predicted the onset of depressive symptoms, with adjustment for
      demographic characteristics and changes in household assets, neighborhood
      poverty, and visible neighborhood disorder. A large increase in the number of
      notices of default (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.14,
      2.67) and properties returning to ownership by the bank (OR = 1.62; 95% CI =
      1.06, 2.47) were associated with depressive symptoms. A large increase in
      properties going to auction was suggestive of such an association (OR = 1.45; 95%
      CI = 0.96, 2.19). Age, fewer years of education, and functional limitations also
      were predictive. CONCLUSIONS: Increases in neighborhood-level foreclosure
      represent an important risk factor for depression in older adults. These results
      accord with previous studies suggesting that the effects of economic crises are
      typically first experienced through deficits in emotional well-being.

PMID- 24446831
TI  - Whole-genome amplification for the detection of molecular targets and minimal
      residual disease monitoring in acute lymphoblastic leukaemia.
AB  - Accurate genomic characterization requires sufficient amounts of optimal quality
      DNA. An approach for increasing the DNA amount is the whole-genome amplification
      (WGA) method. We applied WGA to the molecular quantification and minimal residual
      disease (MRD) evaluation of acute lymphoblastic leukaemia (ALL), aiming to
      compare the results obtained from genomic DNA and amplified DNA with WGA, and to
      evaluate the applicability and the reliability of WGA-DNA. Twenty paired samples
      from adult ALL patients were sequenced to identify the functional germline V-D-J
      segment at diagnosis; real-time quantitative polymerase chain reaction (RQ-PCR)
      quantitative analysis was performed both at diagnosis and follow-up. Genomic DNA
      and WGA-DNA screening identified equivalent 87 rearrangements. At diagnosis, the
      quantitative evaluation of genomic DNA samples showed 1 logarithm difference to
      WGA-DNA samples; these levels are comparable, being within the degree of
      acceptability and confidence. In the follow-up samples, RQ-PCR analysis on
      genomic DNA and WGA showed concordant MRD results in 16/18 samples, while 2/18
      were MRD-positive outside the quantitative range by RQ-PCR (i.e. <5 * 10(-5)) on
      genomic DNA and MRD-negative on WGA-DNA. WGA-DNA enables: (i) the design of
      accurate targets for MRD evaluation in ALL patients, (ii) accurate disease
      quantification at diagnosis, (iii) MRD quantification comparable to genomic DNA.

PMID- 24446833
TI  - 3D amorphous silicon on nanopillar copper electrodes as anodes for high-rate
      lithium-ion batteries.
AB  - We present an amorphous Si anode deposited on a Cu nanopillar current collector,
      fabricated using a thermal roll-to-roll process followed by electroformation and
      LPCVD, for application in high-rate Li-ion batteries. Cu nanopillar current
      collectors with diameters of 250 and 500 nm were patterned periodically with 1
      MUm pitch and 2 MUm height to optimize the diameters of the pillars for better
      electrochemical performance. Void spaces between Cu nanopillars allowed not only
      greater effective control of the strain caused by the Si expansion during
      lithiation than that allowed by a nonpatterned electrode but also significantly
      improved cycle performance even at 20 C measured after the same rate test: After
      100 cycles at 0.5 C, the patterned electrodes with 250 and 500 nm diameter
      nanopillars showed high capacity retentions of 86% and 84%, respectively. These
      electrodes retained discharge capacities of 1057 and 780 mAh/g even at 20 C,
      respectively. 

PMID- 24446832
TI  - Influence of aqueous phase emulsifiers on lipid oxidation in water-in-walnut oil
      emulsions.
AB  - Effects of selected aqueous phase emulsifiers on lipid oxidative stability of
      water-in-walnut oil (W/O) emulsions stabilized by polyglycerol polyricinoleate
      (PGPR) were evaluated. The formation of primary oxidation products (lipid
      hydroperoxides) and secondary oxidation products (headspace hexanal) increased
      with increasing dodecyltrimethylammonium bromide (DTAB) concentration (0.1-0.2 wt
      % of emulsions). In contrast, the addition of sodium dodecyl sulfate (SDS) in the
      aqueous phase reduced lipid hydroperoxide and hexanal formation. In addition, the
      presence of Tween 20 in the aqueous phase did not significantly influence lipid
      oxidation rates in W/O emulsions compared to the control (without Tween 20). Whey
      protein isolate (WPI) was observed to inhibit lipid oxidation in the W/O
      emulsions (0.05-0.2 wt % of emulsions). Aqueous phase pH had an important impact
      on the antioxidant capability of WPI, with higher pH improving its ability to
      inhibit lipid oxidation. The combination of WPI and DTAB in the aqueous phase
      suppressed the prooxidant effect of DTAB. The combination of WPI and SDS resulted
      in improved antioxidant activity, with inhibition being greater at pH 7.0 than at
      pH 3.0. These results suggest that the oxidative stability of W/O emulsions could
      be improved by the use of suitable emulsifiers in the aqueous phase. 

PMID- 24446834
TI  - Systems toxicology approach to understand the kinetics of benzo(a)pyrene uptake,
      biotransformation, and DNA adduct formation in a liver cell model.
AB  - Cell-based models are important for deriving mechanistic information about stress
      response pathways that have evolved to protect cells from toxic insult, such as
      exposure to environmental pollutants. One determinant of the stress response is
      the amount of chemical entering the cell and the cell's ability to detoxify and
      remove the chemical. If the stress response is overwhelmed, an adverse outcome
      will ensue. It was the goal of our study to quantify uptake and elimination rates
      of benzo(a)pyrene (BaP), a ubiquitous environmental pollutant, in a murine liver
      cell line. We evaluated the kinetic behavior in the context of BaP uptake,
      biotransformation, DNA adduct formation and repair along with the transcriptional
      and cell proliferation response. A low (50 nM) and a high (5 MUM) BaP
      concentration were chosen in order to differentiate the role of exposure
      concentration in the time-resolved interaction of BaP with cells. While rates of
      uptake and the initial transcriptional response were similar for both BaP
      concentrations, cells exposed to 50 nM BaP completely recovered from exposure
      within 24 h, whereas cells exposed to 5 MUM BaP did not. Biotransformation
      proceeded faster on 50 nM BaP, and the few DNA adducts formed were completely
      repaired after transient cell cycle arrest. In contrast, DNA adducts greatly
      accumulated in cells exposed to 5 MUM BaP, despite significant biotransformation;
      complete cell cycle arrest and toxicity evolved. On the basis of the kinetic rate
      constants and cellular response, we conclude that at least short-term, pulsed
      exposures to 50 nM BaP, which we consider environmentally relevant, can be
      handled by cells without adverse outcome. Further studies are needed to determine
      the ability of cells to recover from repeated exposure. Our study emphasizes the
      importance of quantifying chemical uptake and fate in cell models to
      differentiate a stress response from an adverse outcome for better risk
      assessment.

PMID- 24446836
TI  - Meprobamate-induced fixed drug eruption.
AB  - Meprobamate is usually a safe drug prescribed for anxiety disorders. Fixed drug
      eruption (FDE) is an exceptional cutaneous adverse effect of this drug. We report
      a case of FDE induced by meprobamate with positive patch test. A 22-year-old
      woman was prescribed for depression meprobamate, aceprometazine, valpromide and
      lorazepam. On the second day of treatment, the patient presented red erythematous
      and pruriginous plaques in the limbs and the face. After stopping the previous
      treatment, the patient's lesions resolved completely within 3 weeks with residual
      pigmentation. One month later, patch tests were performed and were positive to
      meprobamate. Exceptional cases of FDE were reported in literature with
      meprobamate. None has reported the use of patch test to confirm the diagnosis. 

PMID- 24446837
TI  - Nursing practice in nutritional care: a comparison between a residential aged
      care setting and a hospital setting.
AB  - AIM: To explore the similarities and differences in the nursing practice in
      nutritional care between a residential aged care setting and a hospital setting.
      BACKGROUND: Despite being preventable and treatable, undernutrition remains a
      problem for many older people in residential aged care and hospital settings.
      Nurses have a crucial role in assisting people who are unable to eat
      independently and are uniquely positioned to implement solutions that will lead
      to better nutritional care. DESIGN: During 2007-2010, an action research study
      was conducted, underpinned by the principles of the participatory world view to
      address undernutrition in a residential aged care setting and a hospital setting.
      METHODS: The multimethod approach of data and between-method triangulation were
      used to collect and analyse qualitative non-participant observations and action
      research group data. Non-participant observations and action research group data
      were qualitatively analysed using the Analytic Hierarchy. FINDINGS: How nurses
      chose to participate in the provision of nutritional care and assert their
      autonomy when changing practice to nutritional care affected the quality of the
      resident/patient mealtime experience. Operational efficiency influenced the
      choices that nurses made about the type of intervention to implement to improve
      nursing practice in nutritional care. Nurses required management approval to
      change practice in nutritional care. CONCLUSION: The reasons for undernutrition
      are multifactorial and more research is needed to investigate the organizational
      structures and processes that affect the delivery of nutritional care across role
      functions, how these affect the continuity of care and the nurses' role in
      defining the culture around resident/patient mealtimes.

PMID- 24446838
TI  - Tunable "nano-shearing": a physical mechanism to displace nonspecific cell
      adhesion during rare cell detection.
AB  - We report a tunable alternating current electro-hydrodynamic (ac-EHD) force which
      drives lateral fluid motion within a few nanometers of an electrode surface.
      Because the magnitude of this fluid shear force can be tuned externally (e.g.,
      via the application of an ac electric field), it provides a new capability to
      physically displace weakly (nonspecifically) bound cellular analytes. To
      demonstrate the utility of the tunable nanoshearing phenomenon, we present data
      on purpose-built microfluidic devices that employ ac-EHD force to remove
      nonspecific adsorption of molecular and cellular species. Here, we show that an
      ac-EHD device containing asymmetric planar and microtip electrode pairs resulted
      in a 4-fold reduction in nonspecific adsorption of blood cells and also captured
      breast cancer cells in blood, with high efficiency (approximately 87%) and
      specificity. We therefore feel that this new capability of externally tuning and
      manipulating fluid flow could have wide applications as an innovative approach to
      enhance the specific capture of rare cells such as cancer cells in blood. 

PMID- 24446839
TI  - Assessing the cultural in culturally sensitive printed patient-education
      materials for Chinese Americans with type 2 diabetes.
AB  - Type 2 diabetes affects Chinese Americans at an alarming rate. To address this
      health disparity, research in the area of cultural sensitivity and health
      literacy provides useful guidelines for creating culturally appropriate health
      education. In this article, we use discourse analysis to examine a group of
      locally available, Chinese- and English-language diabetes print documents from a
      surface level and deep structure level of culture. First, we compared these
      documents to research findings about printed health information to determine
      whether and how these documents apply current best practices for health literacy
      and culturally appropriate health communication. Second, we examined how diabetes
      as a disease and diabetes management is being constructed. The printed materials
      addressed surface level culture through the use of Chinese language, pictures,
      foods, and exercises. From a deeper cultural level, the materials constructed
      diabetes management as a matter of measurement and control that contrasted with
      previous research suggesting an alternative construction of balance. A nuanced
      assessment of both surface and deeper levels of culture is essential for creating
      health education materials that are more culturally appropriate and can lead to
      increased health literacy and improved health outcomes.

PMID- 24446840
TI  - Calpha-H carries information of a hydrogen bond involving the geminal hydroxyl
      group: a case study with a hydrogen-bonded complex of 1,1,1,3,3,3-hexafluoro-2
      propanol and tertiary amines.
AB  - Experimental measurement of the contribution of H-bonding to intermolecular and
      intramolecular interactions that provide specificity to biological complex
      formation is an important aspect of macromolecular chemistry and structural
      biology. However, there are very few viable methods available to determine the
      energetic contribution of an individual hydrogen bond to binding and catalysis in
      biological systems. Therefore, the methods that use secondary deuterium isotope
      effects analyzed by NMR or equilibrium or kinetic isotope effect measurements are
      attractive ways to gain information on the H-bonding properties of an alcohol
      system, particularly in a biological environment. Here, we explore the anharmonic
      contribution to the C-H group when the O-H group of 1,1,1,3,3,3-hexafluoro-2
      propanol (HFP) forms an intermolecular H-bond with the amines by quantum
      mechanical calculations and by experimentally measuring the H/D effect by NMR.
      Within the framework of density functional theory, ab initio calculations were
      carried out for HFP in its two different conformational states and their H-bonded
      complexes with tertiary amines to determine the (13)C chemical shielding, change
      in their vibrational equilibrium distances, and the deuterium isotope effect on
      (13)C2 (secondary carbon) of HFP upon formation of complexes with tertiary
      amines. When C2-OH was involved in hydrogen bond formation (O-H as hydrogen
      donor), it weakened the geminal C2-H bond; it was reflected in the NMR chemical
      shift, coupling constant, and the equilibrium distances of the C-H bond. The
      first derivative of nuclear shielding at C2 in HFP was -48.94 and -50.73 ppm A(
      1) for anti and gauche conformations, respectively. In the complex, the values
      were -50.28 and -50.76 ppm A(-1), respectively. The C-H stretching frequency was
      lower than the free monomer, indicating enhanced anharmonicity in the C-H bond in
      the complex form. In chloroform, HFP formed a complex with the amine; deltaC2 was
      69.107 ppm for HFP-triethylamine and 68.766 ppm for HFP-d2-triethylamine and the
      difference in chemical shift, the DeltadeltaC2 was 341 ppb. The enhanced
      anharmonicity in the hydrogen-bonded complex resulted in a larger vibrational
      equilibrium distance in C-H/D bonds. An analysis with the Morse potential
      function indicated that the enhanced anharmonicity encountered in the bond was
      the origin of a larger isotope effect and the equilibrium distances. Change in
      vibrational equilibrium distance and the deuterium isotope effect, as observed in
      the complex, could be used as parameters in monitoring the strength of the H-bond
      in small model systems with promising application in biomacromolecules. 

PMID- 24446841
TI  - Guidelines for psychological practice with older adults.
AB  - The "Guidelines for Psychological Practice With Older Adults" are intended to
      assist psychologists in evaluating their own readiness for working with older
      adults and in seeking and using appropriate education and training to increase
      their knowledge, skills, and experience relevant to this area of practice. The
      specific goals of these professional practice guidelines are to provide
      practitioners with (a) a frame of reference for engaging in clinical work with
      older adults and (b) basic information and further references in the areas of
      attitudes, general aspects of aging, clinical issues, assessment, intervention,
      consultation, professional issues, and continuing education and training relative
      to work with this group. The guidelines recognize and appreciate that there are
      numerous methods and pathways whereby psychologists may gain expertise and/or
      seek training in working with older adults. This document is designed to offer
      recommendations on those areas of awareness, knowledge, and clinical skills
      considered as applicable to this work, rather than prescribing specific training
      methods to be followed. The guidelines also recognize that some psychologists
      will specialize in the provision of services to older adults and may therefore
      seek more extensive training consistent with practicing within the formally
      recognized specialty of Professional Geropsychology (APA, 2010c).

PMID- 24446842
TI  - Irwin L. Goldstein (1937-2013).
AB  - Irwin L. Goldstein-known as Irv by everyone-was born in New York City on October
      4, 1937 and died on March 18, 2013. Irv loved ideas, especially good theoretical
      ideas that had practical applications. He was both a scholar and a practitioner
      of industrial psychology. At various times, he was associate editor of both the
      Journal of Applied Psychology and Human Factors, and his very influential book
      Training in Organizations (1974) went through four editions. The Society for
      Industrial and Organizational Psychology (SIOP) benefited enormously from his
      efforts on its behalf. If you chatted with Irv about any of his administrative
      positions, but especially about this last one, you would hear how much he felt,
      once again, that he was learning and how excited he was about what was actually
      possible in higher education. Irv retired from this position in 2012. In his many
      academic administrative roles, Irv was a mentor to all-graduate students,
      faculty, department chairs, and deans as well. Irv had had excellent role models
      to work from, and he cared for excellence and hard work-always with a twinkle in
      his eyes.

PMID- 24446843
TI  - J. Richard Hackman (1940-2013).
AB  - When J. Richard Hackman died in Cambridge, Massachusetts, on January 8, 2013,
      psychology lost a giant. Six-and-a-half feet tall, with an outsize personality to
      match, Richard was the leading scholar in two distinct areas: work design and
      team effectiveness. In both domains, his work is foundational. Throughout his
      career, Richard applied rigorous methods to problems of great social importance,
      tirelessly championing multilevel analyses of problems that mattered. His impact
      on our field has been immense. Richard rescued the field of groups research from
      a state of stagnation. Although embarrassed by awards, Richard received many of
      them. For decades to come, our field will be uplifted by Richard's example, to
      better see how we can all strive for excellence in research, in teaching, and in
      having an impact on the world.

PMID- 24446844
TI  - Eugene Irvine Taylor Jr. (1946-2013).
AB  - Eugene Irvine Taylor Jr. was born on October 28, 1946 and died on January 30,
      2013. Eugene systematically applied the techniques of historical scholarship in
      comparative religions to archival reconstructions in the history of American
      psychology and psychiatry. Eugene regarded the history and philosophy of
      psychology as a vocation, devoting himself to the neglected histories of clinical
      and folk psychology.

PMID- 24446845
TI  - Joseph F. Rychlak (1928-2013).
AB  - Joseph Frank Rychlak was born on December 17, 1928 and passed away on April 16,
      2013. Joe's major contributions to psychology vary widely, as mentioned, but they
      are all carefully connected to a rigorously humanistic understanding of the
      person. It may be stretching it to use the phrase "one of the last grand
      theorists" to describe him and his contribution to psychology. There are still
      many important living theorists in the field. However, it is not an exaggeration
      to use the term "grand" because Rychlak's work is nothing if not subsuming,
      spanning not only the personality and psychotherapy literatures but also works on
      cognition, humanism, and the philosophy of science. Throughout his long and
      productive examination of these ideas, Joe remained a man of the highest
      integrity, vision, and caring.

PMID- 24446846
TI  - Maurice J. Zemlick (1924-2013).
AB  - Maurice J. Zemlick was born on March 8, 1924 and passed away March 1, 2013. He
      will be remembered as a master clinician who was strongly committed to
      excellence, competence, and accountability in the training of psychologists. He
      was a Navy veteran who was one of the founders of the California School of
      Professional Psychology (CSPP). Maury was the recipient of many awards and
      honors. Maury was instrumental in the growth and development of psychology as a
      profession and particularly in the professional school movement. He was also
      committed to providing quality professional services to the community. As a
      mentor, Maury was known for his personal and professional integrity.

PMID- 24446847
TI  - Jacob Max Rabbie (1927-2013).
AB  - Jacob Max Rabbie, an internationally renowned social psychologist and a founding
      member of the European Association of Social Psychology (EASP), died on June 29,
      2013. Jaap was born in Haarlem, the Netherlands, on October 4, 1927. Jaap studied
      social psychology at the University of Amsterdam and became the face of Dutch
      social psychology. His later research focused on aggression between individuals
      and groups, his early work attempted to isolate the minimal conditions that
      suffice to generate discriminatory ingroup-outgroup attitudes. Jaap was a
      dedicated and passionate scientist, oriented to getting things right even when
      this meant going against the current stream.

PMID- 24446848
TI  - Vigilance phenomena, cognitive workload, and fatigue.
AB  - Comments on the original record by Hancock (see record 2012-28202-001) regarding
      the problem of iatrogenically created psychological phenomena. This comment
      offers a solution to two of the problems that Hancock identified in his
      integrative review of vigilance research. First, the performance decrement over
      time that can set in within a half hour of performing a vigilance task in the
      laboratory is much less likely to occur in real-world conditions; performance
      improvements have also been noted. Second, a paradigm shift in the framing of
      questions and experimental designs is probably required to further research on
      these phenomena, which appear to grow in complexity (Hancock, 2013, p. 107).

PMID- 24446849
TI  - Finding vigilance through complex explanations for complex phenomena.
AB  - Replies to comments by Guastello (see record 2014-01475-008) on the original
      article by the current author (see record 2012-28202-001) regarding the problem
      of iatrogenically created psychological phenomena. Guastello offered a
      sympathetic, meaningful, and potentially explanatory account of several of the
      issues raised in the recent article. The purpose of this reply is to evaluate his
      offered hypotheses and to see where this intriguing line of development might
      lead in terms of theoretical and practical understanding of the critical real
      world capacity of vigilance. What Guastello correctly identified is that
      vigilance, or more correctly, the application of human sustained attention to an
      external task, represents one facet of what Freeman (1948) identified generally
      as the "energetic" dimensions of human behavioral capacity.

PMID- 24446850
TI  - A phenomenologist's response to Alan Waterman.
AB  - Comments on the article "The humanistic psychology-positive psychology divide:
      Contrasts in philosophical foundations" by Waterman (see record 2013-12501-001).
      Distancing positive psychology from humanistic psychology, Alan Waterman wishes
      to close the conversation between the two cognate psychological paradigms. It's
      true that strong fences can make good neighbors, and a desire for amicable
      separation on the basis of irreconcilable differences is understandable. The
      current author believes that Waterman's gracious style is an exemplary model for
      respectful disagreement. However, in distancing positive psychology from
      humanistic psychology generally, Waterman represented phenomenology as the
      philosophical foundation to humanistic psychology in a way that is seriously
      mistaken at worst and problematic at best. Putting aside the issue of the
      relationship between phenomenology and humanistic psychology (as well as positive
      psychology), this brief commentary will limit itself to those points where
      Waterman invoked the term phenomenological with broad strokes that invite
      friendly clarification.

PMID- 24446851
TI  - A therapist's response to Alan Waterman.
AB  - Comments on the article "The humanistic psychology-positive psychology divide:
      Contrasts in philosophical foundations" by Waterman (see record 2013-12501-001).
      Alan Waterman's article brought a useful discerning eye to the differences
      between humanistic and positive psychology and their different theoretical and
      methodological assumptions. It is important that these differences not be glossed
      over too quickly by those who seek complementarity or integration of the two.
      However, Waterman also polarized them unnecessarily, which is unfortunate.

PMID- 24446852
TI  - Are humanistic and positive psychology really incommensurate?
AB  - Comments on the article "The humanistic psychology-positive psychology divide:
      Contrasts in philosophical foundations" by Waterman (see record 2013-12501-001).
      Waterman has provided some broad-brush generalizations about differences between
      humanistic psychology and positive psychology, many of which do not hold in all
      cases, and he has pointed out some difficulties that would be involved in
      reconciling them. However, he has not presented any convincing argument that the
      two are irreconcilable. Essentially, Waterman has confounded difficulties with
      impossibilities by concluding these are incommensurate.

PMID- 24446853
TI  - Practicing what we preach in humanistic and positive psychology.
AB  - Comments on the article "The humanistic psychology-positive psychology divide:
      Contrasts in philosophical foundations" by Waterman (see record 2013-12501-001).
      With a largely backward glance cast toward humanistic psychology's early
      successes, Waterman's article concluded by turning toward positive psychology's
      "vibrant" future and pointed to irreconcilable differences that would limit
      further dialogue between the two fields. From the current authors' perspective,
      such an assessment results in premature closure on the relationship between the
      two subdisciplines, as we in the humanistic tradition continue to appreciate and
      place our trust in the power of dialogue. Psychologists on both sides of this
      epistemological boundary might therefore benefit from focusing on the
      possibilities offered by an interface between the two approaches rather than on a
      divide that is far more likely to push us apart.

PMID- 24446854
TI  - Humanistic and positive psychology need each other, and to advance, our field
      needs both.
AB  - Comments on the article "The humanistic psychology-positive psychology divide:
      Contrasts in philosophical foundations" by Waterman (see record 2013-12501-001).
      Alan Waterman's article is an illuminating contribution that will be reviewed and
      debated for years to come. The current author is appreciative of Waterman for
      raising key questions about the respective worldviews of humanistic and positive
      psychology and their potential for rapprochement. That said, the current author
      thinks Waterman's conclusion that both perspectives are better off pursuing their
      own independent agendas is a short-sighted one that is likely to have
      debilitating, if not dire, effects on the future of our profession. The current
      author believes that there are many ways for existential-humanistic and positive
      psychology researchers to collaborate.

PMID- 24446855
TI  - Further reflections on the humanistic psychology-positive psychology divide.
AB  - Replies to comments by Morley (see record 2014-01475-010), Serlin (see record
      2014-01475-011), Friedman (see record 2014-01475-012), Churchill and Mruk (see
      record 2014-01475-013), and Schneider (see record 2014-01475-014) on the current
      author's original article "The humanistic psychology-positive psychology divide:
      Contrasts in philosophical foundations" (see record 2013-12501-001). The article
      contrasting humanistic psychology and positive psychology with respect to their
      ontological, epistemological, and practical philosophical foundations has
      generated commentaries from leading proponents of varying perspectives within
      humanistic psychology. There is a great deal of material within those
      commentaries with which the current author is in full accord. It is worth noting
      at the outset that no one appears to be challenging the observations (a) that
      published exchanges between proponents of humanistic and positive psychology have
      been marked by tension and ambivalence, albeit with occasional efforts at
      reconciliation and rapprochement; (b) that proponents of the two perspectives
      differ with respect to the philosophers they most frequently cite in their
      writings; or (c) that such citations reflect the philosophical assumptions
      serving as foundations for the theoretical, research, and counseling/therapeutic
      endeavors of psychologists in both groups. The principal points of concurrence in
      the critiques published here are that the current underestimates the extent to
      which mutually supportive, collaborative work can be accomplished across the
      philosophical divide and that the recommendations the current author has made has
      advanced serious potential negative consequences for the field. The current
      author will address these points here in the reply, although space does not
      permit him to address other substantive points raised by individual commentators.

PMID- 24446856
TI  - Sub-Saharan Africa's HIV pandemic.
AB  - Longitudinal studies and household surveys suggest that sub-Saharan Africa's
      (SSA's) HIV/AIDS crisis is not a pandemic of the poor but rather one of
      inequalities, where wealthier individuals are more likely to be infected as a
      result of greater mobility and multiple relationships (Fox, 2012). This is in
      sharp contrast to the situation in the United States, where HIV infections "are
      concentrated among the poor with very few people in the middle and upper social
      strata contracting HIV" (Pellowski, Kalichman, Matthews, & Adler, May-June 2013,
      p. 199). Yet from a global perspective, wherein SSA is the poorest region in the
      world, the pandemic is of course one of poverty as well as one with pronounced
      racial and gender disparities. Both the May-June 2013 special issue of the
      American Psychologist ("HIV/AIDS: Social Determinants and Health Disparities")
      and another American Psychologist special issue 25 years earlier ("Psychology and
      AIDS," November 1988) help shed light on Africa's HIV/AIDS crisis.

PMID- 24446857
TI  - Iron(II) complexes containing unsymmetrical P-N-P' pincer ligands for the
      catalytic asymmetric hydrogenation of ketones and imines.
AB  - After their treatment with LiAlH4 and then alcohol, new iron dicarbonyl complexes
      mer-trans-[Fe(Br)(CO)2(P-CH?N-P')][BF4] (where P-CH?N-P' = R2PCH2CH?NCH2CH2PPh2
      and R = Cy or iPr or P-CH?N-P' = (S,S)- Cy2PCH2CH?NCH(Me)CH(Ph)PPh2) are
      catalysts for the hydrogenation of ketones in THF solvent with added KOtBu at 50 
      degrees C and 5 atm H2. Complexes with R = Ph are not active. With the
      enantiopure complex, alcohols are produced with an enantiomeric excess of up to
      85% (S) at TOF up to 2000 h(-1), TON of up to 5000, for a range of ketones. An
      activated imine is hydrogenated to the amine in 90% ee at a TOF 20 h(-1)and TON
      99. This is a significant advance in asymmetric pressure hydrogenation using
      iron. The complexes are prepared in two steps: (1) a one-pot reaction of
      phosphonium dimers ([cyclo-(PR2CH2CH(OH)(-))2][Br]2), KOtBu, FeBr2, and
      Ph2PCH2CH2NH2 (or (S,S)-Ph2PCH(Ph)CH(Me)NH2 for the enantiopure complex) in THF
      under a CO atmosphere to produce the complexes cis- and trans-[Fe(Br)2(CO)(P-CH?N
      P')]; (2) the reaction of these with AgBF4 under CO(g) to afford the dicarbonyl
      complexes in high yield (50-90%). NMR and DFT studies of the process of
      precatalyst activation show that the dicarbonyl complexes are converted first to
      hydride-aluminum hydride complexes where the imine of the P-CH?N-P' ligand is
      reduced to an amide [P-CH2N-P'](-) with aluminum hydrides still bound to the
      nitrogen. These hydride species react with alcohol to give monohydride amine iron
      compounds FeH(OR')(CO)(P-CH2NH-P'), R' = Me, CMe2Et as well as the iron(0)
      complex Fe(CO)2(P-CH2NH-P') under certain conditions. 

PMID- 24446858
TI  - What is your diagnosis? Cerebrospinal fluid from a dog.

PMID- 24446859
TI  - Automation of blood component preparation from whole blood collections.
AB  - BACKGROUND AND OBJECTIVES: Automation of blood component preparation (BCP) from
      whole blood (WB) collections is increasingly being widespread implemented. This
      review summarizes the quality of blood components obtained with new automated
      devices. MATERIALS AND METHODS: We reviewed available literature on the quality
      of blood components obtained with new automated devices developed in the 2000s.
      RESULTS: Blood components obtained with the new devices met European standards.
      Of note, compared with platelet concentrates obtained with manual methods,
      automation of BCP improved the consistency of the final products. CONCLUSION: The
      complete automation of BCP from WB collections is still in development and it
      represents a huge change in paradigm.

PMID- 24446860
TI  - Preparation and characterization of novel lipid carriers containing microalgae
      oil for food applications.
AB  - This work investigated the suitability of lipid carriers as potential
      encapsulation method to improve the physical and chemical stability of microalgae
      oil high in docosahexaenoic acid (DHA). Lipid carriers with various oil contents
      were successfully prepared by a microfluidization method using stearic acid as
      solid lipid, microalgae oil as liquid lipid, and poloxamer 188 as surfactant.
      Results show that the mean particle diameter of the lipid carriers was in the
      range of 300 to 350 nm with the polydispersity index below 0.2. The lipid
      carriers were found to have spherical shape when examined under the transmission
      electron microscope. Data from the encapsulation efficiency and loading capacity
      indicate high distribution of microalgae oil throughout the lipid carriers and
      good physical stability as reflected by the particle size and size distribution
      during storage. Furthermore, the lower DPPH scavenging activity of lipid carriers
      compared with that of free microalgae oil suggests better chemical stability of
      microalgae oil encapsulated in lipid carriers. The addition of microalgae oil
      into lipid phase could disturb the crystalline order and form lattice defects to
      enable encapsulation of DHA as revealed by the results from differential scanning
      calorimetery. Current results suggest that this type of novel lipid carriers
      could be an efficient and promising carrier system for delivery of microalgae
      oil. 

PMID- 24446861
TI  - An unusual onset of supraventricular tachycardia with 2:1 atrioventricular block:
      what is the mechanism?

PMID- 24446862
TI  - Functional characterization of kinetochore protein, Ctf19 in meiosis I: an
      implication of differential impact of Ctf19 on the assembly of mitotic and
      meiotic kinetochores in Saccharomyces cerevisiae.
AB  - Meiosis is a specialized cell division process through which chromosome numbers
      are reduced by half for the generation of gametes. Kinetochore, a multiprotein
      complex that connects centromeres to microtubules, plays essential role in
      chromosome segregation. Ctf19 is the key central kinetochore protein that
      recruits all the other non-essential proteins of the Ctf19 complex in budding
      yeast. Earlier studies have shown the role of Ctf19 complex in enrichment of
      cohesin around the centromeres both during mitosis and meiosis, leading to sister
      chromatid cohesion and meiosis II disjunction. Here we show that Ctf19 is also
      essential for the proper execution of the meiosis I specific unique events, such
      as non-homologous centromere coupling, homologue pairing, chiasmata resolution
      and proper orientation of homologues and sister chromatids with respect to the
      spindle poles. Additionally, this investigation reveals that proper kinetochore
      function is required for faithful chromosome condensation in meiosis. Finally,
      this study suggests that absence of Ctf19 affects the integrity of meiotic
      kinetochore differently than that of the mitotic kinetochore. Consequently,
      absence of Ctf19 leads to gross chromosome missegregation during meiosis as
      compared with mitosis. Hence, this study reports for the first time the
      differential impact of a non-essential kinetochore protein on the mitotic and
      meiotic kinetochore ensembles and hence chromosome segregation. 

PMID- 24446863
TI  - Umbilical laparoendoscopic urological surgery with a novel reusable device.
AB  - OBJECTIVE: The aims of this study were to present cumulative experience with
      umbilical laparoendoscopic urological surgery using a reusable device and to
      evaluate outcomes and complications in the first 100 patients. MATERIAL AND
      METHODS: Patients undergoing umbilical surgery with the KeyPort system and
      DuoRotate instruments (Richard Wolf, Knittlingen, Germany) were evaluated
      prospectively. Demographic, intraoperative and postoperative data were assessed.
      RESULTS: Between October 2011 and July 2012, 79 pelvic (66 radical prostatectomy,
      10 radical cystectomy, one diverticulectomy, one bilateral orchiectomy, one
      ureter reimplantation) and 21 renal (seven radical nephrectomy, six partial
      nephrectomy, five nephroureterectomy, two pyeloplasty, one pyelolithotomy)
      surgeries were performed through the umbilicus using this platform. Follow-up was
      56.7 +/- 12.6 weeks (mean +/- SD). Mean age was 64.3 +/- 10.3 years, body mass
      index 29 +/- 4.6 kg/m(2), operative time 232 +/- 106 min and estimated blood loss
      260 +/- 95 ml. Conversion to standard multiport laparoscopy was not necessary. An
      accessory port was used in 87 cases to facilitate suturing and conduct drainage
      extraction. Postoperative complications occurred in 24 cases (six Clavien grade
      I, 12 grade II, one grade IIIa, two grade IIIb, two grade IVa, one grade IVb).
      Mean hospital stay was 4.2 +/- 4 days. Total transfusion rate was 10%. Mean
      visual analogue pain scale at day 2 was 2.1 +/- 1.3 (0-10). Visual analogue wound
      satisfaction scale at month 1 was 9.2 +/- 0.6 (0-10). No cancer-related events
      occurred during follow-up. Late complications (4%) were not related to the
      surgical approach. CONCLUSIONS: Umbilical KeyPort surgery is technically feasible
      for a great variety of procedures, both ablative and reconstructive. This access
      offers adequate surgical outcomes, scarce postoperative pain and security for the
      patient in the short term. Its reusable nature implies a noticeable economic
      advantage.

PMID- 24446864
TI  - Phenolic compounds of apple cultivars resistant or susceptible to Venturia
      inaequalis.
AB  - CONTENT: Phenolic compounds play an important role in the plant defense mechanism
      and are responsible for antioxidant capacity in fruits and vegetables. It is
      known that the phenolics can determine in the leaves of plants which are
      resistant/susceptible to fungal infections. OBJECTIVE: This study investigated
      the total phenolic compounds, content of shikimic acid from 33 different apple
      cultivars leaves infected with Venturia inaequalis [(Cke). Wint.] cultured in
      Fruit Research Station, in Egirdir, Isparta, Turkey. MATERIALS AND METHODS:
      Leaves of apple cultivars were collected three times in an interval of 30 d from
      July to September in 2010, and analyzed using HPLC methods to detect changes in
      the amount of the phenolic compounds and shikimic acid. RESULTS: Total phenolic
      compounds and shikimic acid in resistant/moderate susceptible apple cultivars
      were higher than susceptible apple cultuvars, although not statistically
      different between resistant and susceptible apples. The content of shikimic acid
      was statistically higher only in the leaves of the domestic cultivar Ankara
      guzeli on all three dates. DISCUSSION AND CONCLUSION: Recently, there have been
      increased studies trying to explain the resistance mechanism in plants. Natural
      resistance genes are investigated in some apple cultivars and new resistance
      varieties which have resistant genes are identified daily. Our study hold to
      determine the relationship between the phenolic compounds and the expression of
      resistance seems to be promising.

PMID- 24446865
TI  - A novel enzyme-dependent melatonin metabolite in humans.
AB  - Exogenous melatonin is widely used in humans for multiple pharmacologic purposes.
      The metabolic pathways of melatonin reflect the fate and functions of melatonin
      in vivo. This study was designed to re-profile melatonin metabolism in humans
      using a metabolomic approach. In the urine of healthy subjects treated with 10 mg
      melatonin, sulfate- or glucuronide-conjugated metabolites of melatonin were
      detected, including 6-hydroxymelatonin sulfate, 6-hydroxymelatonin glucuronide, N
      acetylserotonin glucuronide, N-acetylserotonin sulfate, and an unknown sulfated
      metabolite (X). The molecular weight of metabolite X was 14 Da smaller than 6
      hydroxymelatonin sulfate, but 16 Da larger than N-acetylserotonin sulfate.
      Further studies suggest that metabolite X was produced via O-demethylation, 6
      hydroxylation, and sulfation. The antioxidant products of melatonin, N(1)-acetyl
      N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxy-kynuramine, were not
      detected in human urine. In summary, this study provided a global view of
      melatonin metabolism in humans and extended our knowledge of enzyme-dependent
      pathways of melatonin metabolism.

PMID- 24446866
TI  - Long-term Abeta exposure augments mCa2+-independent mROS-mediated depletion of
      cardiolipin for the shift of a lethal transient mitochondrial permeability
      transition to its permanent mode in NARP cybrids: a protective targeting of
      melatonin.
AB  - Mitochondrial dysfunction is a hallmark of amyloid beta-peptide (Abeta)-induced
      neurodegeneration of Alzheimer's disease (AD). This study investigated whether
      mtDNA T8993G mutation-induced complex V inhibition, clinically associated with
      neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP), is a
      potential risk factor for AD and the pathological link for long-term exposure of
      Abeta-induced mitochondrial toxicity and apoptosis in NARP cybrids. Using
      noninvasive fluorescence probe-coupled laser scanning imaging microscopy and NARP
      cybrids harboring 98% mutant genes along with its parental 143B osteosarcoma
      cells, we demonstrated that Abeta-augmented mitochondrial Ca(2+) (mCa(2+))
      independent mitochondrial reactive oxygen species (mROS) formation for a
      cardiolipin (CL, a major mitochondrial protective phospholipid)-dependent lethal
      modulation of the mitochondrial permeability transition (MPT). Abeta augmented
      not only the amount but also the propagation rate of mROS-induced mROS formation
      to significantly depolarize mitochondrial membrane potential (?Psi(m)) and reduce
      mCa(2+) stress. Abeta-augmented mROS oxidized and depleted CL, thereby enhances
      mitochondrial fission and movement retardation, which promoted the NARP-augmented
      lethal transient-MPT (t-MPT) to switch to its irreversible mode of permanent-MPT
      (p-MPT). Interestingly, melatonin, a multiple mitochondrial protector, markedly
      reduced Abeta-augmented mROS formation and therefore significantly reduced mROS
      mediated depolarization of ?Psi(m), fission of mitochondria and retardation of
      mitochondrial movement to stabilize CL and hence the MPT. In the presence of
      melatonin, Abeta-promoted p-MPT was reversed to a protective t-MPT, which
      preserved ?Psi(m) and lowered elevated mCa(2+) to sublethal levels for an
      enhanced mCa(2+)-dependent O(2) consumption. Thus, melatonin may potentially
      rescue AD patients associated with NARP symptoms.

PMID- 24446867
TI  - Intravascular haemolysis secondary to Clostridium perfringens in a patient with
      acute myeloid leukaemia undergoing allogeneic stem cell transplantation.

PMID- 24446870
TI  - Best practices for intrathecal drug delivery for pain.
AB  - OBJECTIVE: The objective of this study was to identify best practices and provide
      guidance to clinicians to ensure safety and optimize intrathecal drug delivery
      for chronic intractable pain. METHODS: Twelve experienced pain medicine
      practitioners-eight anesthesiologists, one neurosurgeon, one physiatrist, one
      clinical psychologist, and one advanced practice registered nurse-from the United
      States, Australia, and Europe gathered to identify and publish consensus on best
      practices in three areas related to safe intrathecal therapy for pain: safety and
      monitoring, patient and device management, and patient selection and trialing.
      CONCLUSIONS: Intrathecal drug delivery is a valuable alternative drug delivery
      system for many patients with severe chronic or end-of-life pain. While device
      related complications (mostly with catheters) and surgical-site infections can
      occur, the main therapy-related safety issues associated with intrathecal drug
      delivery arise primarily with inadequate patient monitoring (e.g., respiratory
      depression), inflammatory mass (e.g., high doses and concentrations of opioids),
      wound healing, dosing errors (e.g., medication concentration and pump
      programming), pump fills or refills (e.g., pocket fills), and interaction with
      concomitant systemic medications (e.g., opioids and benzodiazepines). Many of the
      reported adverse events and complications of intrathecal drug delivery can be
      prevented by adequate clinician training, implementation of best practices, and
      experience. In adopting the therapy, patients must be apprised of its risks and
      benefits. Physicians and patients must partner to achieve both safety and
      effectiveness.

PMID- 24446871
TI  - Self-assembling micelle-like nanoparticles with detachable envelopes for enhanced
      delivery of nucleic acid therapeutics.
AB  - In spite of the great potential of nucleic acids as therapeutic agents, the
      clinical application of nucleic acid therapeutics requires the development of
      effective systemic delivery strategies. In an effort to develop effective nucleic
      acid delivery systems suitable for clinical application, we previously reported a
      self-assembling micelle-like nanoparticle that was based on phospholipid
      polyethylenimine conjugates, i.e., "micelle-like nanoparticles" (MNPs). In this
      study, we aimed to improve the system by enhancing the efficiency of
      intracellular delivery of the payload via pH-responsive detachment of the
      monolayer envelope and release of the nucleic acid therapeutics upon reaching the
      target tissues with an acidic pH, e.g., tumors. The acid-cleavable phospholipid
      polyethylenimine conjugate was synthesized via hydrazone bond, and acid-cleavable
      MNPs were then prepared and characterized as before. We evaluated the acid
      cleavable MNP construct for in vitro and in vivo nucleic acid delivery efficiency
      using cultured tumor cells and tumor-bearing mice. The acid-cleavable nanocarrier
      showed an enhanced cellular delivery at pH 6.5 as compared to pH 7.4, whereas the
      noncleavable nanocarrier did not show any differences. Tail vein injections also
      led to enhanced intracellular uptake of the acid-cleavable nanocarrier compared
      to the noncleavable nanocarrier into tumor cells of tumor-bearing mice although
      no significant difference was observed in total tumor accumulation. 

PMID- 24446872
TI  - Phagocyte depletion inhibits AA amyloid accumulation in AEF-induced huIL-6
      transgenic mice.
AB  - OBJECTIVE: Determine the role of phagocytosis in the deposition of acute phase
      SAA protein in peripheral organs as AA amyloid. METHODS: AA amyloidosis was
      induced by injection of amyloid enhancing factor (AEF) in huIL-6 transgenic mice.
      Clodronate liposomes were injected at different times, and the amyloid load
      evaluated by Congo red birefringence staining and monitoring with the amyloid
      specific probe (125)I-labeled peptide p5R. RESULTS: Injection of clodronate
      containing liposomes depleted Iba-1 positive and F4/80 positive phagocytic cells
      in liver and spleen for up to 5 days. Treatment prior to administration of
      intravenous AEF did not alter the pattern of deposition of the AEF in spleen, but
      inhibited the catabolism of the (125)I-labeled AEF. Clodronate treatment 1 day
      before or 1 day after AEF administration had little effect on AA amyloid
      accumulation at 2 weeks; however, mice treated with clodronate liposomes 5 days
      after AEF induction and evaluated at 2 weeks post-AEF induction showed reduced
      amyloid load relative to controls. At 6 weeks post-AEF there was no significant
      effect on amyloid load following a single clodronate treatment. CONCLUSION:
      Macrophages have been shown to be instrumental in both accumulation and clearance
      of AA amyloid after cessation of inflammation. Our data indicate that when SAA
      protein is continuously present, depletion of phagocytic cells during the early
      course of the disease progression temporarily reduces amyloid load.

PMID- 24446874
TI  - Anti-frameshifting ligand reduces the conformational plasticity of the SARS virus
      pseudoknot.
AB  - Programmed -1 ribosomal frameshifting (-1 PRF) stimulated by mRNA pseudoknots
      regulates gene expression in many viruses, making pseudoknots potential targets
      for anti-viral drugs. The mechanism by which pseudoknots trigger -1 PRF, however,
      remains controversial, with several competing models. Recent work showed that
      high -1 PRF efficiency was linked to high pseudoknot conformational plasticity
      via the formation of alternate conformers. We tested whether pseudoknots bound
      with an anti-frameshifting ligand exhibited a similar correlation between
      conformational plasticity and -1 PRF efficiency by measuring the effects of a
      ligand that was found to inhibit -1 PRF in the SARS coronavirus on the
      conformational dynamics of the SARS pseudoknot. Using single-molecule force
      spectroscopy to unfold pseudoknots mechanically, we found that the ligand binding
      effectively abolished the formation of alternate conformers. This result extends
      the connection between -1 PRF and conformational dynamics and, moreover, suggests
      that targeting the conformational dynamics of pseudoknots may be an effective
      strategy for anti-viral drug design. 

PMID- 24446873
TI  - Identification of clinically important chromosomal aberrations in acute myeloid
      leukemia by array-based comparative genomic hybridization.
AB  - Array-based comparative genomic hybridization (aCGH) chromosomal analysis
      facilitates rapid detection of cytogenetic abnormalities previously undetectable
      by conventional cytogenetics. In this study, we analyzed 48 uniformly treated
      patients with acute myeloid leukemia (AML) by 44K aCGH and correlated the
      findings with clinical outcome. aCGH identified previously undetected
      aberrations, as small as 5 kb, of currently unknown significance. The 36.7 Mb
      minimally deleted region on chromosome 5 lies between 5q14.3 and 5q33.3 and
      contains 634 genes and 15 microRNAs, whereas loss of chromosome 17 spans 3194 kb
      and involves 342 genes and 12 microRNAs. Loss of a 155 kb region on 5q33.3 (p <
      0.05) was associated with achievement of complete remission (CR). In contrast,
      loss of 17p11.2-q11.1 was associated with a lower CR rate and poorer overall
      survival (Kaplan-Meier analysis, p < 0.0096). aCGH detected loss of 17p in 12/48
      patients as compared to 9/48 by conventional karyotyping. In conclusion, aCGH
      analysis adds to the prognostic stratification of patients with AML.

PMID- 24446875
TI  - MoS2/graphene composite paper for sodium-ion battery electrodes.
AB  - We study the synthesis and electrochemical and mechanical performance of layered
      free-standing papers composed of acid-exfoliated few-layer molybdenum disulfide
      (MoS2) and reduced graphene oxide (rGO) flakes for use as a self-standing
      flexible electrode in sodium-ion batteries. Synthesis was achieved through vacuum
      filtration of homogeneous dispersions consisting of varying weight percent of
      acid-treated MoS2 flakes in GO in DI water, followed by thermal reduction at
      elevated temperatures. The electrochemical performance of the crumpled composite
      paper (at 4 mg cm(-2)) was evaluated as counter electrode against pure Na foil in
      a half-cell configuration. The electrode showed good Na cycling ability with a
      stable charge capacity of approximately 230 mAh g(-1) with respect to total
      weight of the electrode with Coulombic efficiency reaching approximately 99%. In
      addition, static uniaxial tensile tests performed on crumpled composite papers
      showed high average strain to failure reaching approximately 2%. 

PMID- 24446876
TI  - Production of monoclonal antibody for okadaic acid and its utilization in an
      ultrasensitive enzyme-linked immunosorbent assay and one-step
      immunochromatographic strip.
AB  - Okadaic acid (OA) is a common marine biotoxin that accumulates in bivalves and
      causes diarrhetic shellfish poisoning (DSP). This study generated a monoclonal
      antibody (mAb) specific to OA from a hybridoma cell line, 6B1A3, which was
      obtained by fusion of myeloma cells (P3/NS1/1-AG4-1) with spleen cells isolated
      from a BALB/c mouse immunized with OA-gamma-globulin. The 6B1A3 mAb belongs to
      the immunoglobulin G1 (kappa chain) isotype. Both competitive direct and indirect
      enzyme-linked immunosorbent assays (ELISAs) were established for characterization
      of the antibody. The concentrations causing 50% inhibition of binding of OA
      horseradish peroxidase to the antibody by OA were calculated to be 0.077 ng/mL in
      the cdELISA. A rapid and sensitive mAb-based gold nanoparticle
      immunochromatographic strip was also established. This proposed strip has a
      detection limit of 5 ng/mL for OA and can be finished in 10 min. Extensive
      analyses of 20 seafood samples with ELISA revealed that 10 were slightly
      contaminated with OA, with a mean concentration of 0.892 ng/g. Analysis of OA in
      shellfish samples showed that data acquired by the immunochromatographic strip
      agreed well with those acquired by the ELISA. The mAb-based ELISA and
      immunochromatographic strip assay developed in this study have adequate
      sensitivity and accuracy for rapid screening of OA in shellfish samples.

PMID- 24446878
TI  - Anisotropic adhesion of micropillars with spatula pads.
AB  - Natural gecko adhesive structures consisting of angled setae, branched into thin
      spatulas, have remarkable properties including easily attachable and releasable
      anisotropic adhesion. The geometrically asymmetric structures lead to anisotropic
      adhesive properties. Inspired by the gecko, we fabricated an array of
      micropillars with asymmetric spatula pads from elastomeric materials. This paper
      describes the anisotropic properties of the micropillars with spatula pads as
      established by experimental measurements and observation together with finite
      element analysis. The results indicate that the structural difference of the
      spatula pad at one edge of the micropillar provides the anisotropic adhesive
      properties. 

PMID- 24446877
TI  - Conformational ordering of biomolecules in the gas phase: nitrogen collision
      cross sections measured on a prototype high resolution drift tube ion mobility
      mass spectrometer.
AB  - Ion mobility-mass spectrometry measurements which describe the gas-phase scaling
      of molecular size and mass are of both fundamental and pragmatic utility.
      Fundamentally, such measurements expand our understanding of intrinsic
      intramolecular folding forces in the absence of solvent. Practically,
      reproducible transport properties, such as gas-phase collision cross-section
      (CCS), are analytically useful metrics for identification and characterization
      purposes. Here, we report 594 CCS values obtained in nitrogen drift gas on an
      electrostatic drift tube ion mobility-mass spectrometry (IM-MS) instrument. The
      instrument platform is a newly developed prototype incorporating a uniform-field
      drift tube bracketed by electrodynamic ion funnels and coupled to a high
      resolution quadrupole time-of-flight mass spectrometer. The CCS values reported
      here are of high experimental precision (+/-0.5% or better) and represent four
      chemically distinct classes of molecules (quaternary ammonium salts, lipids,
      peptides, and carbohydrates), which enables structural comparisons to be made
      between molecules of different chemical compositions for the rapid "omni-omic"
      characterization of complex biological samples. Comparisons made between helium
      and nitrogen-derived CCS measurements demonstrate that nitrogen CCS values are
      systematically larger than helium values; however, general separation trends
      between chemical classes are retained regardless of the drift gas. These results
      underscore that, for the highest CCS accuracy, care must be exercised when
      utilizing helium-derived CCS values to calibrate measurements obtained in
      nitrogen, as is the common practice in the field. 

PMID- 24446879
TI  - Cultural dilemmas of choice: Deconstructing consumer choice in health
      communication between maternity-care providers and ethnic Chinese mothers in New
      Zealand.
AB  - This article critically analyses the discourse of consumer choice embedded in
      health communication interactions between maternity-care providers and migrant
      ethnic Chinese mothers in New Zealand. Findings indicate that Chinese mothers, as
      the customers of the New Zealand maternity and health care services, are
      encouraged to "fit in" with the Western discourse of choice. However, the
      mothers' cultural predispositions for childbirth and communication have a
      significant impact on the ways in which they respond to and resist this
      discourse. Drawing on theoretical insights from postcolonialism and Third World
      feminism, this article contributes to the study of intercultural health
      communication by examining cultural dilemmas in the discourse of choice that is
      often taken for granted in Western health contexts. In doing so, it builds a
      platform for an inclusive maternity care and health environment in multicultural
      societies.

PMID- 24446882
TI  - Rutile (beta-)MnO2 surfaces and vacancy formation for high electrochemical and
      catalytic performance.
AB  - MnO2 is a technologically important material for energy storage and catalysis.
      Recent investigations have demonstrated the success of nanostructuring for
      improving the performance of rutile MnO2 in Li-ion batteries and supercapacitors
      and as a catalyst. Motivated by this we have investigated the stability and
      electronic structure of rutile (beta-)MnO2 surfaces using density functional
      theory. A Wulff construction from relaxed surface energies indicates a rod-like
      equilibrium morphology that is elongated along the c-axis, and is consistent with
      the large number of nanowire-type structures that are obtainable experimentally.
      The (110) surface dominates the crystallite surface area. Moreover, higher index
      surfaces than considered in previous work, for instance the (211) and (311)
      surfaces, are also expressed to cap the rod-like morphology. Broken coordinations
      at the surface result in enhanced magnetic moments at Mn sites that may play a
      role in catalytic activity. The calculated formation energies of oxygen vacancy
      defects and Mn reduction at key surfaces indicate facile formation at surfaces
      expressed in the equilibrium morphology. The formation energies are considerably
      lower than for comparable structures such as rutile TiO2 and are likely to be
      important to the high catalytic activity of rutile MnO2. 

PMID- 24446880
TI  - Young adult follow-up of adolescent girls in juvenile justice using the Columbia
      suicide severity rating scale.
AB  - This study focused on the reliability and validity of the Columbia Suicide
      Severity Scale (C-SSRS). Severely delinquent adolescent girls (n = 166)
      participated in a treatment trial and repeated assessments over time. Lifetime
      suicide attempt history was measured using the C-SSRS in early adulthood (n =
      144; 7-12 years postbaseline). Nonclinician raters showed strong interrater
      reliability using the C-SSRS. Self-reports, caseworker reports, and caregiver
      reports of girls' suicide attempt histories collected at baseline correlated with
      adult participants' recollections of their baseline attempt histories. Suicidal
      ideation measured prospectively across a 7- to -12-year period was associated
      with retrospectively reported suicide attempt across the same period. 

PMID- 24446885
TI  - Theoretical study of hydrogen permeation through mixed NiO-MgO films supported on
      Mo(100): role of the oxide-metal interface.
AB  - This work presents a periodic density functional study of the adsorption and
      permeation of atomic H on Ni-doped MgO oxide thin films supported on a Mo(100)
      surface. We find that the binding of atomic H is affected by the presence of a
      metallic support. The chemisorption energies increase considerably when the oxide
      film is supported. The H permeation through the NiO-MgO oxide was also studied. H
      migration through the unsupported NiO-MgO oxide is thermodynamically inhibited,
      while the presence of the metallic Mo makes permeation thermodynamically favored.
      We attribute the promoting effect to the different character of adsorbed H at the
      unsupported Ni-doped MgO oxide and at the oxide-Mo interface. In the former case,
      H forms hydroxyl groups, whereas in the latter case it appears as hydride due to
      the formation of strong metal-hydrogen bonds. These results illustrate the
      important role that the oxide-metal interface could play in the mechanism for
      pure and mixed oxides reduction. 

PMID- 24446886
TI  - Post-transcriptional silencing of UIS4 in Plasmodium berghei sporozoites is
      important for host switch.
AB  - Plasmodium sporozoites are transmitted by mosquitoes and first infect hepatocytes
      of their mammalian host, wherein they develop as liver stages, surrounded by the
      parasitophorous vacuole membrane (PVM). The parasite must rapidly adapt to its
      changing environment after switching host. Shortly after invasion, the PVM is
      remodelled by insertion of essential parasite proteins of the early transcribed
      membrane protein family such as UIS4. Here, using the rodent malaria model
      Plasmodium berghei, we show that transcripts encoding UIS4 are stored in a
      translationally repressed state in sporozoites, allowing UIS4 protein synthesis
      only after host cell invasion. Using a series of reporter transgenic parasite
      lines we could demonstrate that the open reading frame of UIS4 mRNA is critical
      for gene silencing, whereas the 5' and 3' untranslated regions are dispensable.
      Our data further indicate that the UIS4 translational repression machinery is
      present only in mature sporozoites in the mosquito salivary glands, and that
      premature expression of UIS4 protein results in a loss of parasite infectivity.
      Our findings reveal the importance of specific post-transcriptional control in
      sporozoites, and establish that host switch requires high levels of
      translationally silent UIS4 RNA, which permits stage conversion, yet avoids
      premature expression of this liver stage-specific protein. 

PMID- 24446887
TI  - Electrochemical impedance spectroscopy as an alternative to determine dielectric
      constant of potatoes at various moisture contents.
AB  - The dielectric (DE) properties, specifically the DE constant (epsilon') and loss
      factor (epsilon''), were measured for vacuum-dried and freeze-dried potato
      samples at a microwave frequency of 2.45 GHz over a range of different moisture
      contents (MCs) using a DE probe and also a 2-probe electrochemical impedance
      spectroscopy (EIS). Third-order polynomial models (epsilon' = f1(MC); and
      epsilon'' = f2(MC)) at room temperature were developed for regression analysis.
      Additionally, at various temperatures (T), biphasic 3rd-order polynomial models
      (epsilon' = f1(MC, T); and epsilon'' = f2(MC, T)) were obtained to determine
      epsilon' and epsilon'' as a function of MC and T using measured data. The vacuum
      dried potato sample showed a good fitness of epsilon' and epsilon'' (R2 = 0.95
      and 0.96, respectively) to the regression model with the range of MCs from 18% to
      80% (w/w), while the freeze-dried potato sample showed a good fitness of epsilon'
      and epsilon'' to the 1st-phase regression model with MC < 50% w/w (R2 = 0.95 and
      0.96, respectively) and the 2nd-phase regression model with MC > 50% w/w (R2 =
      0.94 to 0.96). EIS measurements were also used to obtain correlation impedances
      for epsilon' and epsilon'' determined by the DE probe method. The resulted
      regression analysis meets the demands for simple, rapid, and accurate assessment
      for transient values of epsilon' and epsilon'' of food products during
      dehydration/drying processes. The EIS method was verified to be a successful
      alternative to direct measurements of epsilon' and epsilon''.

PMID- 24446888
TI  - Selective serotonin reuptake inhibitors for premature ejaculation: review of
      erectile and ejaculatory side effects.
AB  - Premature ejaculation is one of the most prevalent sexual disorders affecting men
      today. The lack of approved therapies has resulted in the prescription of many
      'off-label' treatments to manage the condition. Selective serotonin reuptake
      inhibitors have an interesting side effect of prolonging ejaculatory latency.
      Consequently, these agents are often considered a first line treatment for
      patients suffering from premature ejaculation. Erectile dysfunction is another
      common side effect reported by men treated with selective serotonin reuptake
      inhibitors. Nitric oxide is the primary mediator of erectile function.
      Preclinical studies have provided evidence that selective serotonin reuptake
      inhibitors decrease nitric oxide bioavailability. This invited mini-review aims
      to examine the physiology of the erectile and ejaculatory responses, discuss the
      indicated and 'off-label' clinical utility of selective serotonin reuptake
      inhibitors, and to summarize evidence from basic science and clinical studies
      pertaining to mechanisms of how selective serotonin reuptake inhibitor therapy
      modifies ejaculatory and erectile function. 

PMID- 24446889
TI  - Safety of canagliflozin in patients with type 2 diabetes.
AB  - Canagliflozin is a newly approved drug for the treatment of type 2 diabetes. This
      agent lowers blood glucose mainly by increasing urinary glucose excretion through
      inhibition of sodium glucose co-transporter 2 (SGLT2) in the kidneys. Data
      derived from randomized clinical trials lasting up to 52 weeks suggest that
      canagliflozin is generally well tolerated. The most common adverse effects are
      genital mycotic infections occurring in 11-15% of women exposed to canagliflozin
      versus 2-4% of those randomized to glimepiride or sitagliptin. In men,
      corresponding proportions are 8-9% versus 0.5-1%. Urinary tract infections (UTI)
      are slightly increased (5-7%) with the use of canagliflozin compared with placebo
      (4%). The risk of hypoglycemia associated with canagliflozin is marginally higher
      than placebo, but markedly increases when the drug is used in conjunction of
      insulin or sulfonylureas (SU), in patients with chronic kidney disease (CKD), and
      in the elderly. Worsening renal function and hyperkalemia may occur in patients
      using canagliflozin, particularly in patients with underlying CKD. Mild weight
      loss (mean 2-4 kg) and lowering of blood pressure represent 2 advantages of
      canagliflozin owing to its osmotic diuretic effect. However, the latter action
      may lead to postural hypotension and dizziness in susceptible subjects. Another
      concerning adverse effect of canagliflozin is an average 8% increase in plasma
      levels of low-density lipoprotein cholesterol (LDL-C) compared with placebo.
      Overall, canagliflozin is a useful addition for treatment of type 2 diabetes, but
      its safety needs to be established in long-term clinical trials. 

PMID- 24446890
TI  - Antibiotics and non-steroidal anti-inflammatory drugs in outpatient practice:
      indications and unwanted effects in a gastroenterological setting.
AB  - OBJECTIVE: To explore the type and frequency of the unwanted effects following
      use of non-steroidal antiinflammatory drugs (NSAIDs) and antibiotics in a
      gastroenterological out-patient setting. METHODS: We analyzed a
      gastroenterological database which includes 151 inflammatory bowel disease (IBD)
      patients followed between January 2008 and December 2009. The key-words included
      NSAIDs and antibiotics. RESULTS: Of 19 cases treated with NSAIDs, 8 displayed
      convincing evidence linking them with the subsequent development of IBD. Of 44
      antibiotic mentions, 7 documents alluded to macrolide prescriptions, which were
      followed by induction or relapse of IBD in 5; all of the newly diagnosed cases of
      IBD were endoscopically proven, and one ran a fulminant course requiring
      emergency colectomy; 4 of 5 prescriptions of amoxycillin/clavulanic acid were
      accompanied by toxicity (three hepatitides and one reactivated IBD). Overall, the
      frequency of unwanted effects was 36% for both NSAIDs and antibiotics.
      CONCLUSION: We suggest that NSAIDs and antibiotics (specifically of the macrolide
      structure) can induce gut and hepatic damage, significantly enhancing co
      morbidities in gastroenterologic out-patients, with break of cost-containment
      guidelines. Therefore, caution is advisable in prescribing NSAIDs and antibiotics
      in this setting. Though retrospective and possibly biased, the current data
      coincide with both bench work and epidemiological evidence.

PMID- 24446891
TI  - The effect of left ventricular electrical delay on the acute hemodynamic response
      with cardiac resynchronization therapy.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) improves hemodynamic
      function, as well as reduces hospitalizations and mortality among patients with
      systolic dysfunction, QRS prolongation, and heart failure. The magnitude of the
      hemodynamic response is associated with improved outcomes, so optimization of
      this parameter is a goal of therapy. The purpose of this study was to evaluate
      the effect of left ventricular (LV) electrical delay, as assessed by the QLV
      interval, on the acute hemodynamic response to CRT. METHODS AND RESULTS: This
      study included 31 patients undergoing biventricular ICD placement. At implant,
      invasive LV dP/dt was measured by a micromanometer catheter during biventricular
      (BV) or LV only pacing. Both atrial sensing (AS) and atrial pacing (AP) modes
      were evaluated at 5 different AV delays, tested in randomized order. The QLV
      interval was measured at the LV pacing site. Compared with intrinsic rhythm, CRT
      increased LV dP/dtmax by 9.5 +/- 8.8% with BV pacing and 10.0 +/- 9.2% with LV
      pacing (P = 0.38) during AS. With AP, CRT increased LV dP/dtmax by 16.0 +/- 10.8%
      and 15.3 +/- 11.1%, respectively (P = 0.47). QLV was strongly correlated with the
      hemodynamic response in all pacing configurations. Multivariate analysis showed
      that with BV pacing QLV was an independent predictor of the hemodynamic response
      with a 1.7% increase in %LV dP/dt for every 10 milliseconds prolongation of QLV.
      CONCLUSIONS: LV electrical delay is a strong predictor of the acute hemodynamic
      response to CRT. This relationship is independent of pacing mode.

PMID- 24446892
TI  - The prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1)
      gene in central serous chorioretinopathy and its association with plasma PAI-1
      levels.
AB  - CONTEXT: Central serous chorioretinopathy (CSCR) is a poorly understood disease
      and the choroidal circulation abnormality induced by the plasminogen activator
      inhibitor type 1 (PAI-1) seems to be associated with the pathogenesis. There are
      many reports indicating that 4 G/5 G polymorphism of the PAI-1 gene is a risk
      factor for several diseases related to the elevated serum levels of PAI-1.
      OBJECTIVE: To evaluate the 4 G/5 G polymorphism of the PAI-1 gene and its
      association with serum levels of PAI-1 in acute CSCR patients. MATERIALS AND
      METHODS: Sixty CSCR patients and 50 healthy control patients were included. The
      PAI-1 4 G/5 G was genotyped using the polymerase chain reaction-restriction
      technique. Serum PAI-1 level was measured using enzyme-linked immunosorbent
      assay. Demographic data consisting of age, sex, body mass index (BMI) as well as
      genotype disturbances and serum PAI-1 levels were compared between the groups.
      Statistical significance for differences in the serum PAI-1 levels of each group
      with different genotypes was also analyzed. RESULTS: The CSCR group consisted of
      40 male (66.7%) and 20 female (33.3%) patients with a mean age of 46.7 +/- 8.39
      years. The control group consisted of 32 male (64%) and 18 female (36%) healthy
      subjects with a mean age of 45.8 +/- 8.39 years. There was no statistically
      significant difference between the groups in terms of age, sex and BMI. In the
      CSCR group the genotype frequencies were 4 G/4G: 30% (n = 18), 4G/5 G: 50% (n =
      30), 5 G/5G: 20% (n = 12) and in the control group genotype frequencies were 34%
      (n = 17), 42% (n = 21) and 24% (n = 12), respectively. There was no statistically
      significant difference in the distribution of genotypes among the groups (chi
      squared, p = 0.70). The CSCR group had a significantly higher serum PAI-1
      concentration than the control group (p = 0.001). In both groups the mean plasma
      PAI-1 concentration did not vary significantly among the different genotypes (p >
      0.05). DISCUSSION AND CONCLUSION: Although our results demonstrated that the
      patients with acute CSCR have higher serum PAI-1 concentrations than the
      controls, no significant difference was found in the genotype disturbances of the
      PAI-1 gene between the groups. The current study indicates that 4 G/5 G
      polymorphism in the promoter of the PAI-1 gene cannot be considered a risk factor
      for the elevated serum PAI-1 levels and consequent development of CSCR.

PMID- 24446893
TI  - A questionnaire-based survey of dry eye disease among leather tannery workers in
      Kanpur, India: a case-control study.
AB  - CONTEXT: Kanpur is a major leather processing center in India, where a large
      number of tanneries are situated. During tanning process, workers are constantly
      exposed to heat, leather dust produced in buffering operations and a wide range
      of chemicals. All these factors are known to cause dry eye. Being
      ophthalmologists of a tertiary health care center in Kanpur, we used to notice
      over a period of time that a considerable number of patients with dry eye
      symptoms, attending our out-patient department, were related to leather tanning
      industries. But, no published data is available on the prevalence of and risk
      factors for dry eye disorders among tannery worker. OBJECTIVE: To estimate the
      prevalence of dry eye problem and its severity among the workers of leather
      tanneries in the industrial belt of Kanpur and to evaluate various risk factors
      related to it. METHODS: In this cross-sectional case-control study, Ocular
      Surface Disease Index (OSDI) Questionnaire was presented to randomly selected
      tannery workers and control group. OSDI score was calculated based on subjects'
      response, and was evaluated with OSDI chart to assess the magnitude of dry eye
      symptoms and to grade its severity. RESULTS were analyzed statistically to
      evaluate the significance level. RESULTS: A total of 800 workers were selected by
      simple random sampling, out of which 72 workers were excluded from the study.
      Thus the questionnaire was presented to a total of 728 workers, while control
      group included 260 individuals. All the workers as well as controls were male
      with age ranging from 20 to 59 years. The mean age for tannery workers was 34.05
      +/- 8.96 years and that for control group was 32.97 +/- 10.59 years (p = 0.14).
      The tannery workers had mean duration of work at tanneries for 6.99 +/- 4.86
      years. The prevalence of dry eye symptoms among tannery workers was 33.79% (95%
      CI: 30.35-37.24), while that in control group was 15.77% (95% CI: 11.31-20.23) (p
      < 0.0001). Among symptomatic workers, 47.96% (95% CI: 41.68-54.26) workers had
      mild, 36.99% (95% CI: 30.91-43.07) workers had moderate and 15.04% (95% CI: 10.54
      19.54) workers had severe dry eye symptoms. Severe symptoms were more prevalent
      among symptomatic workers of age >= 40 years in comparison to those <40 years
      (34.72% versus 6.90%, p < 0.0001). With increase in duration of work (1-5, 6-15
      and 16-25 years), both prevalence and severity of dry eye symptoms increased
      significantly (p = 0.036 and <0.0001, respectively). CONCLUSION: Dry eye is a
      significantly prevalent occupational hazard among tannery workers, severity of
      which increases with the age and the duration of work in tannery. Chemical
      exposure in hot and dusty working environment of a tannery may have a causative
      role. Tannery workers should be motivated to use various preventive measures to
      reduce chemical and dust exposure such as wearing protective glasses, and their
      ocular health should be monitored periodically for adequate and timely treatment,
      if required.

PMID- 24446894
TI  - Determining a core curriculum in surgical infections for fellowship training in
      acute care surgery using the Delphi technique.
AB  - BACKGROUND: Recent data highlight the educational, financial, and healthcare
      benefits of acute care surgery (ACS). These data serve as the impetus to create
      ACS fellowships, which now are accredited by the American Association for the
      Surgery of Trauma. However, the core components of a curriculum fundamental for
      ACS training and that yield competence and proficiency have yet to be determined.
      METHODS: Experts in ACS from the United States (n=86) were asked to propose
      topics in surgical infectious diseases of potential importance in developing a
      core curriculum for ACS fellowship training. They were then required to rank
      these topics in order of importance to identify those considered most
      fundamental. RESULTS: Thirty-one filters ranking in the highest tertile are
      proposed as topics of surgical infectious diseases that are fundamental to any
      curriculum of ACS fellowship training. The majority pertains to aspects of
      thoracic infections (n=8), although topics of soft tissue infections (n=5)
      comprised four of the top 10 (40%) filters. Abdominal infections (n=6), the
      biology of sepsis (n=6), and risk, prevention, and prophylaxis (n=6) completed
      the list. CONCLUSION: This study identifies the most important topics of surgical
      infectious disease that merit consideration for incorporation into a core
      curriculum of ACS training. Hopefully, this information will assist in the
      development of ACS fellowships that optimize the training of future ACS surgeons.

PMID- 24446895
TI  - Poly-epsilon-caprolactone mesh as a scaffold for in vivo tissue engineering in
      rabbit esophagus.
AB  - Repair of long-gap esophageal atresia is associated with a high degree of
      complications. Tissue engineering on a scaffold of a bioresorbable material could
      be a solution. The aim of the present study was to investigate the in vivo tissue
      engineering of smooth muscle cells and epithelium on a poly-epsilon-caprolactone
      mesh in rabbit esophagus. Twenty female rabbits had a window of 0.6 * 1 cm cut in
      the abdominal part of the esophagus. The defect was covered with a poly-epsilon
      caprolactone mesh. The rabbits were killed on postoperative day 28-30, and mesh
      with surrounding esophagus was removed for histological examination. Fifteen
      rabbits survived the trial period. Six had no complications and had the mesh in
      situ. They all had ingrowth of epithelial and smooth muscle cells and an almost
      completely degraded mesh. Nine rabbits developed pseudo-diverticula. It proved
      possible to engineer both epithelial and smooth muscle cells on the poly-epsilon
      caprolactone mesh in spite of a fast mesh degradation. The latter may be the
      explanation to the development of pseudo-diverticula; this is a problem that
      needs attention in future experimental trials.

PMID- 24446896
TI  - Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide
      administration.
AB  - Protein and peptide drugs administered subcutaneously, such as insulin can be
      amyloidogenic and result in localized amyloid deposits at the sites of medication
      injections. These iatrogenic amyloidoses typically present as a localized
      subcutaneous nodule or skin reaction at the site of administration, and often
      pose diagnostic challenges. We have analyzed the amyloid proteome in 52 cases of
      insulin and enfuvirtide associated amyloidosis using laser microdissection/tandem
      mass spectrometry. We show that the deposits are composed of the drug, as well as
      other amyloid precursor proteins such as apolipoproteins A-I, A-IV, E and serum
      amyloid protein. Mass spectrometry-based amyloid sub-typing allows for accurate
      amyloid diagnosis with resultant therapeutic and prognostic implications. This
      insight into the amyloid proteome in drug-induced amyloidosis may help further
      understand pathogenesis of amyloid fibril formation.

PMID- 24446897
TI  - Plasma antibody profiles in non-human primate tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) in non-human primates (NHPs) is highly contagious,
      requiring efficient identification of animals infected with Mycobacterium
      tuberculosis. Tuberculin skin test is usually used but lacks desirable
      sensitivity/specificity and efficiency. METHODS: We aimed to develop an
      immunoassay for plasma antibodies against M. tuberculosis. A key challenge is
      that not all infected animals contain antibodies against the same M. tuberculosis
      antigen. Therefore, a multiplex panel of 28 antigens (Luminex((r)) -Platform) was
      developed. RESULTS: Data revealed antibodies against eight antigens (Rv3875,
      Rv3875-Rv3874 fusion, Rv3874, Rv0934, Rv3881, Rv1886c, Rv2031, Rv3841) in
      experimentally infected (M. tuberculosis strains: Erdman and H37Rv) NHPs (rhesus
      and cynomolgus macaques). In a naturally acquired M. tuberculosis infection,
      rhesus macaques (n = 15) with lung TB pathology (n = 10) contained antibodies to
      five additional antigens (Rv0831, Rv2220, Rv0054, Rv1099, and Rv0129c).
      CONCLUSIONS: Results suggest that this user-friendly and easily implementable
      multiplex panel, containing 13 M. tuberculosis antigens, may provide a high
      throughput alternative for NHP TB screening.

PMID- 24446899
TI  - Estimation and interpretation of fermentation in the gut: coupling results from a
      24 h batch in vitro system with fecal measurements from a human intervention
      feeding study using fructo-oligosaccharides, inulin, gum acacia, and pea fiber.
AB  - Gut bacteria ferment fiber at different rates to primarily short chain fatty
      acids (SCFA) and gas while proteins are metabolized to SCFA, branched chain fatty
      acids (BCFA), gas, and undesirable metabolites. Large volumes of gas produced in
      vivo may contribute to bloating and flatulence in an individual. The objectives
      of this trial were to (1) compare the in vitro fermentation profiles of fructo
      oligosaccharides (FOS), inulin, gum acacia, and pea fiber alone or blended using
      a 24 h batch model and (2) relate these findings to a human study that fed
      enteral formula fortified with fiber blend (FB) or no fiber (FF). The in vitro
      fermentation of the fiber blend resulted in a delayed pH decrease and gas and
      SCFA production compared to the FOS and inulin. Human samples had higher SCFA on
      FB compared to FF (p = 0.029). BCFA were not different between formulas. By using
      a blend of fibers, we observed a slower fermentation in vitro but still increased
      fecal SCFA when fed to human subjects. 

PMID- 24446898
TI  - Long-term effects of maternal separation on the responsiveness of the circadian
      system to melatonin in the diurnal nonhuman primate (Macaca mulatta).
AB  - Depression is often linked to early-life adversity and circadian disturbances.
      Here, we assessed the long-term impact of early-life adversity, particularly
      preweaning mother-infant separation, on the circadian system's responsiveness to
      a time giver or synchronizer (Zeitgeber). Mother-reared (MR) and peer-reared (PR)
      rhesus monkeys were subjected to chronic jet-lag, a forced desynchrony protocol
      of 22 hr T-cycles [11:11 hr light:dark (LD) cycles] to destabilize the central
      circadian organization. MR and PR monkeys subjected to the T-cycles showed split
      locomotor activity rhythms with periods of ~22 hr (entrained) and ~24 hr (free
      running), simultaneously. Continuous melatonin treatment in the drinking water
      (20 MUg/mL) gradually increased the amplitude of the entrained rhythm at the
      expense of the free-running rhythm, reaching complete entrainment by 1 wk. Upon
      release into constant dim light, a rearing effect on anticipation for both the
      predicted light onset and food presentation was observed. In MR monkeys,
      melatonin did not affect the amplitude of anticipatory behavior. Interestingly,
      however, PR macaques showed light onset and food anticipatory activities in
      response to melatonin treatment. These results demonstrate for the first time a
      rearing-dependent effect of maternal separation in macaques, imprinting long-term
      plastic changes on the circadian system well into late adulthood. These effects
      could be counteracted by the synchronizer molecule melatonin. We conclude that
      the melatonergic system is targeted by early-life adversity of maternal
      separation and that melatonin supplementation ameliorates the negative impact of
      stress on the circadian system.

PMID- 24446900
TI  - Predicting continuance-findings from a longitudinal study of older adults using
      an eHealth newsletter.
AB  - While eHealth technologies are promisingly efficient and widespread, theoretical
      frameworks capable of predicting long-term use, termed continuance, are lacking.
      Attempts to extend prominent information technology (IT) theories to the area of
      eHealth have been limited by small sample sizes, cross-sectional designs, self
      reported as opposed to actual use measures, and a focus on technology adoption
      rather than continuance. To address these gaps in the literature, this analysis
      includes empirical evidence of actual use of an eHealth technology over the
      course of one year. This large (n = 4,570) longitudinal study focuses on older
      adults, a population with many health needs and among whom eHealth use may be
      particularly important. With three measurement points over the course of a year,
      this study examined the effects of utilitarian and hedonic beliefs on the
      continued use of an eHealth newsletter using constructs from IT adoption and
      continuance theories. Additional analyses compared the relative strength of
      intentions compared to earlier use in predicting later use. Usage intention was
      strongly predicted by both hedonic beliefs and utilitarian beliefs. In addition,
      utilitarian beliefs had both direct effects on intention and indirect effects,
      mediated by hedonic beliefs. While intention predicted subsequent use, earlier
      use was a significantly stronger predictor of use than intention. These findings
      make a theoretical contribution to an emerging literature by shedding light on
      the complex interplay of reasoned action and automaticity in the context of
      eHealth continuance. 

PMID- 24446901
TI  - Polarization-control of the potential barrier at the electrode interfaces in
      epitaxial ferroelectric thin films.
AB  - Electrode interface is a key element in controlling the macroscopic electrical
      properties of the ferroelectric capacitors based on thin films. In the case of
      epitaxial ferroelectrics, the electrode interface is essential in controlling the
      leakage current and the polarization switching, two important elements in the
      read/write processes of nonvolatile memories. However, the relation between the
      polarization bound charges and the electronic properties of the electrode
      interfaces is not yet well understood. Here we show that polarization charges are
      controlling the height of the potential barriers at the electrode interfaces in
      the case of Pb(Zr,Ti)O3 and BaTiO3 epitaxial films. The results suggest that the
      height is set to a value allowing rapid compensation of the depolarization field
      during the polarization switching, being almost independent of the metals used
      for electrodes. This general behavior open a new perspective in engineering
      interface properties and designing new devices based on epitaxial ferroelectrics.

PMID- 24446902
TI  - On the dual roles of ligands in the synthesis of colloidal metal nanostructures.
AB  - Eloquent routes to colloidal metal nanostructures have emerged in recent years,
      and a central component to any successful nanosynthesis is the initial selection
      of metal complexes with an appropriate ligand environment. This local ligand
      environment may be predetermined by the coordination complex selected as the
      metal precursor; however, recent studies reveal that the ligand environment of
      coordination complexes can be modified through exchange with other components for
      the synthesis that include solvent molecules, capping agents, anions, and even
      reducing agents. Importantly, ligands can often play multiple roles in a
      synthesis and direct the outcome by manipulating the rates of precursor reduction
      and particle coalescence, providing colloidal and facet stabilization and even
      serving as reducing agents themselves. This Feature Article highlights examples
      in which the ligand environments of metal precursors and nanoparticles contribute
      to product formation in multiple ways. Acknowledgment of the dual roles of
      ligands in nanomaterial synthesis will enable new strategies for nanostructures
      by decoupling the often contradictory roles of ligands. 

PMID- 24446910
TI  - Chemically bonded TiO2-bronze nanosheet/reduced graphene oxide hybrid for high
      power lithium ion batteries.
AB  - Although Li-ion batteries have attracted significant interest due to their higher
      energy density, lack of high rate performance electrode materials and intrinsic
      safety issues challenge their commercial applications. Herein, we demonstrate a
      simple photocatalytic reduction method that simultaneously reduces graphene oxide
      (GO) and anchors (010)-faceted mesoporous bronze-phase titania (TiO2-B)
      nanosheets to reduced graphene oxide (RGO) through Ti(3+)-C bonds. Formation of
      Ti(3+)-C bonds during the photocatalytic reduction process was identified using
      electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS)
      techniques. When cycled between 1-3 V (vs Li(+/0)), these chemically bonded TiO2
      B/RGO hybrid nanostructures show significantly higher Li-ion storage capacities
      and rate capability compared to bare TiO2-B nanosheets and a physically mixed
      TiO2-B/RGO composite. In addition, 80% of the initial specific (gravimetric)
      capacity was retained even after 1000 charge-discharge cycles at a high rate of
      40C. The improved electrochemical performance of TiO2-B/RGO nanoarchitectures is
      attributed to the presence of exposed (010) facets, mesoporosity, and efficient
      interfacial charge transfer between RGO monolayers and TiO2-B nanosheets. 

PMID- 24446903
TI  - Correlation of plasma trough levels of imatinib with molecular response in
      patients with chronic myeloid leukemia.
AB  - The present study looked at the correlation between mean trough Imatinib plasma
      levels and molecular response in 131 CML patients on imatinib. Patients receiving
      Glivec versus generic Imatinib were also compared. A ROC curve was constructed to
      estimate a threshold level that correlates with a favourable response. Patients
      were grouped into Responders (bcr/abl ration by RQ-PCR less than 1) and Non
      Responders (ration >= 1). The mean trough imatinib plasma level in the responders
      was significantly higher than in the non responders (p = 0.001). The area under
      ROC curve was 0.733, with best sensitivity (51.85%) and specificity (89.42%) at a
      plasma threshold of 0.988 g/ml [1.675 M]. Levels in the patients on Glivec versus
      generic drug (p > 0.05) were comparable. Trough Imatinib plasma levels may be a
      marker for suboptimal response and may identify patients in whom increase of drug
      dose or change in therapy may be indicated.

PMID- 24446911
TI  - Empirical and theoretical insights into the structural features and host-guest
      chemistry of M8L4 tube architectures.
AB  - We demonstrate a general method for the construction of M8L4 tubular complexes
      via subcomponent self-assembly, starting from Cu(I) or Ag(I) precursors together
      with suitable elongated tetraamine and 2-formylpyridine subcomponents. The
      tubular architectures were often observed as equilibrium mixtures of
      diastereomers having two different point symmetries (D2d or D2 ? D4) in solution.
      The equilibria between diastereomers were influenced through variation in ligand
      length, substituents, metal ion identity, counteranion, and temperature. In the
      presence of dicyanoaurate(I) and Au(I), the D4-symmetric hosts were able to bind
      linear Au(Au(CN)2)2(-) (with two different configurations) as the best-fitting
      guest. Substitution of dicyanoargentate(I) for dicyanoaurate(I) resulted in the
      formation of Ag(Au(CN)2)2(-) as the optimal guest through transmetalation.
      Density functional theory was employed to elucidate the host-guest chemistries of
      the tubes. 

PMID- 24446913
TI  - The good and bad of being fair: effects of procedural and interpersonal justice
      behaviors on regulatory resources.
AB  - The justice literature has paid considerable attention to the beneficial effects
      of fair behaviors for recipients of such behaviors. It is possible, however, that
      exhibiting fair behaviors may come at a cost for actors. In this article, we
      integrate ego depletion theory with organizational justice research in order to
      examine the consequences of justice behaviors for actors. We used an experience
      sampling method in a sample of managerial employees to examine the relations of
      performing procedural justice and interpersonal justice behaviors with subsequent
      changes in actors' regulatory resources. Our results indicate that procedural
      justice behaviors are draining, whereas interpersonal justice behaviors are
      replenishing for actors. Depletion, in turn, adversely affected the performance
      of citizenship behavior, and depletion mediated relations of justice behavior
      with citizenship. Furthermore, 2 traits that impact self-regulatory skills-
      extraversion and neuroticism--moderated the replenishing effects of engaging in
      interpersonal justice behaviors. We conclude by discussing implications and
      avenues for future research.

PMID- 24446915
TI  - Clinical and molecular findings of chronic granulomatous disease in Oman: family
      studies.
AB  - Chronic granulomatous disease (CGD), a rare inherited disorder of the innate
      immune system, results from mutations in any one of the five genes encoding the
      subunits of the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH)
      oxidase enzyme, and is characterized by recurrent life-threatening bacterial and
      fungal infections. Molecular analysis of 14 Omani CGD patients from 10 families,
      diagnosed to have CGD on clinical (recurrent infections) and biochemical grounds
      (positive for both the nitroblue tetrazolium (NBT) test and the dihydrorhodamine
      (DHR-1,2,3 assay), revealed that only one patient had X-linked CGD, with a large
      deletion involving both the gp91-phox gene (CYBB) and the McLeod gene (XK). The
      remaining 13 patients were all homozygotes from a previously described c.579G>A
      (p.Trp193X) mutation in the NCF1 gene on chromosome 7, responsible for autosomal
      recessive CGD (AR-CGD). Although X-linked CGD is the most common type of CGD
      disorder in most population groups, AR-CGD is the most prevalent type in Oman. 

PMID- 24446916
TI  - Determination of caffeine, myosmine, and nicotine in chocolate by headspace solid
      phase microextraction coupled with gas chromatography-tandem mass spectrometry.
AB  - The occurrence of the bioactive components caffeine (xanthine alkaloid), myosmine
      and nicotine (pyridine alkaloids) in different edibles and plants is well known,
      but the content of myosmine and nicotine is still ambiguous in milk/dark
      chocolate. Therefore, a sensitive method for determination of these components
      was established, a simple separation of the dissolved analytes from the matrix,
      followed by headspace solid-phase microextraction coupled with gas chromatography
      tandem mass spectrometry (HS-SPME-GC-MS/MS). This is the first approach for
      simultaneous determination of caffeine, myosmine, and nicotine with a convenient
      SPME technique. Calibration curves were linear for the xanthine alkaloid (250 to
      3000 mg/kg) and the pyridine alkaloids (0.000125 to 0.003000 mg/kg). Residuals of
      the calibration curves were lower than 15%, hence the limits of detection were
      set as the lowest points of the calibration curves. The limits of detection
      calculated from linearity data were for caffeine 216 mg/kg, for myosmine 0.000110
      mg/kg, and for nicotine 0.000120 mg/kg. Thirty samples of 5 chocolate brands with
      varying cocoa contents (30% to 99%) were analyzed in triplicate. Caffeine and
      nicotine were detected in all samples of chocolate, whereas myosmine was not
      present in any sample. The caffeine content ranged from 420 to 2780 mg/kg
      (relative standard deviation 0.1 to 11.5%) and nicotine from 0.000230 to 0.001590
      mg/kg (RSD 2.0 to 22.1%). 

PMID- 24446917
TI  - Effect of receptor occupancy on folate receptor internalization.
AB  - The folate receptor (FR) is a GPI anchored cell surface glycoprotein that
      functions to facilitate folic acid uptake and mediate signal transduction. With
      the introduction of multiple folate-targeted drugs into the clinic, the question
      has arisen regarding how frequently a patient can be dosed with a FR-targeted
      drug or antibody and whether dosing frequency exerts any impact on the
      availability of FR for subsequent rounds of FR-mediated drug uptake. Although the
      rate of FR recycling has been examined in murine tumor models, little or no
      information exists on the impact of FR occupancy on its rate of endocytosis. The
      present study quantitates the number of cell surface FR-alpha and FR-beta
      following exposure to saturating concentrations of a variety of folate-linked
      molecules and anti-FR antibodies, including the unmodified vitamin, folate-linked
      drug mimetics, multifolate derivatized nanoparticles, and monoclonal antibodies
      to FR. We report here that FR occupancy has no impact on the rate of FR
      internalization. We also demonstrate that multivalent conjugates that bind and
      cross-link FRs at the cell surface internalize at the same rate as monovalent
      folate conjugates that have no impact on FR clustering, even though the
      multivalent conjugates traffic through a different endocytic pathway. 

PMID- 24446918
TI  - Effects of maternal care on the development of midbrain dopamine pathways and
      reward-directed behavior in female offspring.
AB  - Variation within mesolimbic dopamine (DA) pathways has significant implications
      for behavioral responses to rewards, and previous studies have indicated long
      term programming effects of early life stress on these pathways. In the current
      study, we examined the impact of natural variations in maternal care in Long
      Evans rats on the development of DA pathways in female offspring and the
      consequences for reward-directed behaviors. We found that tyrosine hydroxylase
      (TH) immunoreactivity in the ventral tegmental area was elevated by postnatal day
      6 in response to maternal licking/grooming (LG), and that these effects were
      sustained into adulthood. Increased TH immunoreactivity was not found to be
      associated with altered epigenetic regulation or transcriptional activation of
      Th, but probably involved LG-associated changes in the differentiation of
      postnatal DA neurons through increased expression of Cdkn1c, and enhanced
      survival of DA projections through LG-associated increases in Lmx1b and brain
      derived neurotrophic factor. At weaning, high-LG offspring had elevated DA
      receptor mRNA levels within the nucleus accumbens and increased conditioned place
      preference for a high-fat diet. In contrast, high-LG, as compared with low-LG,
      juvenile offspring had a reduced preference for social interactions with
      siblings, and haloperidol administration abolished group differences in
      conditioned place preference through a shift towards increased social preferences
      in high-LG offspring. The effects of maternal care on developing DA pathways and
      reward-directed behavior of female offspring that we have observed may play a
      critical role in the behavioral transmission of maternal LG from mother to
      daughter, and account for individual differences in the mesolimbic DA system. 

PMID- 24446919
TI  - Rhinitis is associated with a greater risk of intermittent claudication in
      adults.
AB  - BACKGROUND: Chronic inflammatory airway disorders have been reported to be
      associated with vascular diseases of the heart and central nervous system, but
      their association with peripheral arterial disease (PAD), a high-prevalence
      vascular illness, has not been investigated. OBJECTIVE: To evaluate the
      association of asthma and rhinitis with intermittent claudication, which is a
      typical symptom of PAD. METHODS: The data were collected in the gene-environment
      interaction in respiratory disease survey, a population-based, multicase-control
      study. Participants underwent a standardized interview, skin prick tests and
      pulmonary function tests. The associations between respiratory diseases and
      intermittent claudication (i.e. pain in the leg during walking that disappears
      within 10 min when standing still) were estimated through relative risk ratios
      (RRR) by multinomial logistic regression models. RESULTS: 1174 subjects (aged 20
      64 years, of which 52% were females) underwent clinical examinations and were
      classified into four groups: asthma only (n = 81), asthma-rhinitis overlap (n =
      292), rhinitis only (n = 299) and controls (n = 345). The prevalence of
      intermittent claudication in these groups was, respectively, 2.5%, 3.4%, 6.4% and
      2.3%. After adjusting for smoking habits and a wide range of established and
      potential vascular risk factors, rhinitis without asthma was associated with
      intermittent claudication (RRR:4.63, 95% CI:1.72-12.5), whereas no significant
      association was found with asthma alone (RRR:1.45, 95% CI:0.27-7.76) or asthma
      rhinitis overlap (RRR:2.89, 95% CI:0.91-9.18). Atopy did not modify the observed
      association between intermittent claudication and rhinitis. CONCLUSIONS: Our
      findings suggest that rhinitis is associated with PAD, a predictor of future
      cerebrovascular and cardiovascular events, independently of the presence of
      atopy.

PMID- 24446921
TI  - Congenital esophageal stenosis associated with esophageal atresia.
AB  - Congenital esophageal stenosis (CES) is a rare clinical condition but is
      frequently associated with esophageal atresia (EA). The aim of this study is to
      report the diagnosis, management, and outcome of CES associated with EA. Medical
      charts of CES-EA patients from Lille University Hospital, Sainte-Justine
      Hospital, and Montreal Children's Hospital were retrospectively reviewed.
      Seventeen patients (13 boys) were included. The incidence of CES in patients with
      EA was 3.6%. Fifteen patients had a type C EA, one had a type A EA, and one had
      an isolated tracheoesophageal fistula. Seven patients had associated additional
      malformations. The mean age at diagnosis was 11.6 months. All but two patients
      had non-specific symptoms such as regurgitations or dysphagia. One CES was
      diagnosed at the time of surgical repair of EA. In 12 patients, CES was suspected
      based on abnormal barium swallow. In the remaining four, the diagnostic was
      confirmed by esophagoscopy. Eleven patients were treated by dilation only (1-3
      dilations/patient). Six patients underwent surgery (resection and anastomosis)
      because of failure of attempted dilations (1-7 dilations/patient). Esophageal
      perforation was encountered in three patients (18%). Three patients had
      histologically proven tracheobronchial remnants. CES associated with EA is
      frequent. A high index of suspicion for CES must remain in the presence of EA.
      Dilatation may be effective to treat some of them, but perforation is frequent.
      Surgery may be required, especially in CES secondary to ectopic tracheobronchial
      remnants. 

PMID- 24446920
TI  - Effects of surface treatment and artificial aging on the shear bond strength of
      orthodontic brackets bonded to four different provisional restorations.
AB  - OBJECTIVE: To evaluate the combined effects of material type, surface treatment,
      and thermocycling on the bond strength of orthodontic brackets to materials used
      for the fabrication of provisional crowns. MATERIALS AND METHODS: Four materials
      were included in this study (ProTemp, Trim Plus, Trim II, and Superpont C+B).
      Sixty cylindrical specimens (1 * 3 cm) were prepared from each material and
      equally divided into three groups. The first group was ground with silica carbide
      paper, the second was polished with pumice, and the last group was sandblasted
      with 50-um aluminum oxide particles. Stainless-steel maxillary central incisor
      brackets (Victory Series, 3M) were bonded to the provisional material specimens
      with Transbond XT light-cured composite resin, and half of the specimens from
      each group were thermocycled 500 times in 5 degrees C and 55 degrees C water
      baths. Then the brackets were debonded with shear testing, and the results were
      statistically analyzed by three-way analysis of variance and Tukey's multiple
      comparison tests at alpha  =  0.05. Adhesive Remnant Index (ARI) was also
      identified. RESULTS: Before and after thermocycling, ProTemp materials showed the
      highest shear bond strength with orthodontic brackets (10.3 and 13.1 MPa,
      respectively). The statistical analysis indicated an interaction among the three
      independent variables (P < .05) and statistically significant differences in bond
      strength among provisional materials (P < .001), surface treatments (P < .001),
      and thermocycling (P < .05). According to the ARI, most groups demonstrated
      adhesive failure. CONCLUSIONS: The provisional material type, surface treatment,
      and artificial aging have a significant effect on bond strength. Sandblasting
      treatment exerts a beneficial effect on shear bond strength.

PMID- 24446922
TI  - Fabrication of self-assembled (-)-epigallocatechin gallate (EGCG) ovalbumin
      dextran conjugate nanoparticles and their transport across monolayers of human
      intestinal epithelial Caco-2 cells.
AB  - Nanoparticles have the potential to increase bioavailability of nutraceutical
      compounds such as (-)-epigallocatechin gallate (EGCG). Ovalbumin was conjugated
      with dextran using the Maillard reaction. The resultant ovalbumin-dextran (O-D)
      conjugates were self-assembled with EGCG to form EGCG O-D conjugate nanoparticles
      at pH 5.2 after heating at 80  degrees C for 60 min. Ovalbumin in EGCG O-D
      conjugate nanoparticles was further cross-linked by glutaraldehyde for 24 h at
      room temperature. EGCG O-D conjugate nanoparticles and cross-linked EGCG O-D
      conjugate nanoparticles in aqueous suspension had particle sizes of 285 and 339
      nm, respectively, and showed a spherical morphology. The loading efficiencies of
      EGCG in these two nanoparticles were 23.4 and 30.0%, whereas the loading
      capacities were 19.6 and 20.9%, respectively. These nanoparticles showed positive
      zeta-potentials in a pH range from 2.5 to 4.0 but had negative charges at pH
      >=5.0. EGCG O-D conjugate nanoparticles maintained a particle size of 183-349 nm
      in simulated gastric fluid (SGF) and 188-291 nm in simulated intestinal fluid
      (SIF) at 37  degrees C for 2 h, whereas cross-linked nanoparticles had particle
      sizes of 294-527 nm in SGF and 206-300 nm in SIF. Limited release of EGCG was
      observed in both nanoparticle systems in simulated gastric and intestinal fluids
      without and with digestive enzymes. EGCG O-D conjugate nanoparticles
      significantly enhanced the apparent permeability coefficient (Papp) of EGCG on
      Caco-2 monolayers compared with EGCG solution, suggesting that these
      nanoparticles may improve the absorption of EGCG. 

PMID- 24446923
TI  - Plus ca change: selected papers on speech research from the 1964 issue of the
      Cleft Palate Journal.
AB  - This review is part of a series of papers by the editorial board reflecting on
      the 1964 volume of the journal, thereby marking the 50th anniversary of the Cleft
      Palate Craniofacial Journal. Twelve speech-related contributions from that year
      are reviewed. The papers are sorted into four broad thematic categories:
      quantitative assessment of hypernasality, perceptual assessment of speech,
      radiological imaging of velopharyngeal function, and speech prosthetics. The 1964
      contributions are discussed with regards to their relevance to today's research
      and clinical practice. 

PMID- 24446927
TI  - Using the integrative model of behavioral prediction to identify promising
      message strategies to promote healthy sleep behavior among college students.
AB  - This research used the Integrative Model of Behavioral Prediction (IMBP) to
      examine cognitive predictors of intentions to engage in healthy sleep behavior
      among a population of college students. In doing so, we identify promising
      message strategies to increase healthy sleep behavior during college. In Phase 1,
      members of a small sample of undergraduates (n = 31) were asked to describe their
      beliefs about expected outcomes, norms, and perceived behavioral control
      associated with sleep on an open-ended questionnaire. We analyzed these
      qualitative responses to create a closed-ended survey about sleep-related
      attitudes, perceived norms, control beliefs, behavioral intentions, and behavior.
      In Phase 2, a larger sample of undergraduate students (n = 365) completed the
      survey. Attitudes and perceived behavioral control were the strongest predictors
      of both intentions to engage in sleep behavior and self-reported sleep behavior.
      Control beliefs associated with time management and stress also had substantial
      room to change, suggesting their potential as message strategies to better
      promote healthy sleep behavior in college. We conclude with a broader discussion
      of the study's implications for message design and intervention.

PMID- 24446929
TI  - Ni3S2/Ni-P bilayer coated on polyimide as a Pt- and TCO-free flexible counter
      electrode for dye-sensitized solar cells.
AB  - In this study, we reported an efficient, flexible, and low-cost (Pt-free and
      transparent conducting oxide (TCO)-free) counter electrode (CE) made of a
      polyimide (PI) substrate coated with a Ni3S2/Ni-P bilayer for dye-sensitized
      solar cells (DSCs). The bilayer Ni3S2/Ni-P hybrid film was deposited on a PI
      plastic substrate via a series of wet chemical/electrochemical processes. The
      bottom Ni-P layer was deposited on a PI to replace conventional TCO as a
      conductive layer, and the top Ni3S2 layer was employed as the electrocatalyst for
      I3(-) reduction. On the basis of the extensive electrochemical measurments, the
      as-prepared Ni3S2/Ni-P coated PI flexible CE demonstrated a Pt-like
      electrocatalytic for I3(-) reduction. As a result, the DSC assembled with the
      Ni3S2/Ni-P coated PI flexible CE exhibited an impressive photovoltaic conversion
      efficiency of 6.28% accompanied by a fill factor of 0.63 under 1 sun illumination
      (100 mW cm(-2), AM 1.5), which is comparative to that of the DSC based on the Pt
      coated indium tin oxide/polyethylene naphthalate (ITO/PEN) CE. 

PMID- 24446928
TI  - Does the size-illusion effect on prehensile movements depend on preview duration
      for visuomotor process?
AB  - Given that visual estimation of an object's size is affected by an illusory
      figure, the present study investigates the Ebbinghaus size-illusion effect on
      visuomotor performance within different preview durations for viewing an object
      (no preview, 300, 700, 1500, and 3000 ms) before initiating the movement. Twenty
      participants performed the following actions: (a) grasping the object and (b)
      matching the perceived object size with the finger aperture configuration as in
      the grasping task. The illusion affected the grasping aperture size only in the
      no- and 300-ms preview durations, while the matching aperture was affected across
      all preview conditions. These results suggest that the preview duration
      influences the size illusion to affect the grasping performance, and subjects
      adopt different visuomotor processes, depending on preview duration.

PMID- 24446932
TI  - Characteristics of miniature Cheddar-type cheese made by microbial rennet from
      Bacillus amyloliquefaciens: a comparison with commercial calf rennet.
AB  - Miniature Cheddar-type cheeses were produced using microbial rennet from Bacillus
      amyloliquefaciens (milk-clotting enzyme [MCE]) or calf rennet (CAR). With the
      exception of pH, there were no significant differences in gross composition
      between MCE-cheese (MCE-C) and CAR-cheese (CAR-C). The pH value of CAR-C was
      significantly higher than that of MCE-C at 40 and 60 d of ripening. The total
      nitrogen content of the pH 4.6-soluble fraction obtained from MCE-C was higher
      than that obtained from CAR-C. However, nitrogen content of the 12% TCA-soluble
      fraction was similar between CAR-C and MCE-C. The extent of alpha(s1)-casein and
      beta-casein hydrolysis, measured by urea-PAGE, was similar in both cheese
      samples. The hydrolysis of beta-casein was lower than that of alpha(s1)-casein.
      Different reverse phase-high-performance liquid chromatography peptide profiles
      of ethanol-soluble and ethanol-insoluble fractions were obtained from CAR-C and
      MCE-C. The peptide content in the 2 cheese samples increased throughout ripening;
      the ratio of hydrophobic to hydrophilic peptides was lower in MCE-C than in CAR
      C. Compared with CAR-C, MCE-C was softer as a result of higher protein
      hydrolysis. Microbial rennet from B. amyloliquefaciens contributed to higher
      proteolytic rates, which reduced ripening time.

PMID- 24446933
TI  - The experience and technique in laparoscopic portoenterostomy for biliary
      atresia.
AB  - BACKGROUND: The laparoscopic Kasai operation has been under debate for a long
      time. In this study, we described our experience in laparoscopic portoenterostomy
      for biliary atresia SUBJECTS AND METHODS: The operative experience in 25 cases of
      laparoscopic portoenterostomy for biliary atresia since January 2011 was
      reviewed. For the procedure, operative cholangiography was first performed for
      diagnosis. Laparoscopic Kasai portoenterostomy was performed as in the open
      manner. Electrocoagulation hemostasis was avoided at the porta, where bleeding
      was controlled with direct compression only. The Roux loop was fashioned outside
      of the abdominal cavity through the umbilical incision, and portoenterostomy was
      performed with absorbable sutures. RESULTS: All cases underwent the operation
      successfully without conversion to open surgery. The average time of operation
      was 180-285 minutes (mean, 208 minutes), and the blood loss was 15-30 mL. Twenty
      two (88%) patients had bile drainage postoperatively as indicated by their stool
      color. Jaundice was alleviated in 21 (84%) patients, with total bilirubin
      decreased by a third. Follow-up extended from 3 months to 2 years after the
      operation. Jaundice had completely subsided in 14 (56%) cases, with a normal
      level of bilirubin. Seven patients had an initial decrease in bilirubin, but
      jaundice returned because of cholangitis. Two patients died because their parents
      refused liver transplantation. Two cases underwent successful liver transplants.
      CONCLUSIONS: Laparoscopic portoenterostomy for biliary atresia is safe and
      feasible. It has the advantage of clearer vision, precise operation, and less
      operative trauma. In our experience, the outcome of this surgery is as good as
      open surgery if the surgeons are well experienced.

PMID- 24446934
TI  - Social participation is an important basic right: it demands from all members of
      society adequate action. Introduction.

PMID- 24446935
TI  - Is inclusive education a human right?
AB  - In this article, I question the general idea that inclusive education--i.e., to
      teach all students in one class--is a moral human right. The following discussion
      shows that the widespread view in disability studies that there is a moral human
      right to inclusive education can be reasonably called into question by virtue of
      the proposed counter arguments, but without denying that inclusive education is
      of utmost importance. Practically speaking, the legal human right to inclusive
      education is of great practical value for impaired students, and for their basic
      right to be free from discrimination in education, since their concern thereby
      gains great legal and moral force. But, theoretically speaking, this particular
      human right lacks an attainable consensus concerning proper moral justification.

PMID- 24446936
TI  - Disability and capability: exploring the usefulness of Martha Nussbaum's
      capabilities approach for the UN disability rights convention.
AB  - I explore the usefulness of Martha Nussbaum's capabilities approach in regard to
      the UN Convention on the Rights of Persons with Disabilities (CRPD). The CRPD
      aims at empowering people with disabilities by granting them a number of civil
      and political, but also economic, social and cultural rights. Implementing the
      CRPD will clearly be politically challenging and also very expensive for states.
      Thus, questions might arise as to whether the requirements set in the CRPD can be
      justified from an ethical perspective. I will first investigate if Nussbaum's
      capabilities approach provides support for the rights claimed in the CRPD.
      Second, I will investigate to what extent Nussbaum's capabilities approach is a
      useful tool to set priorities among rights in the course of the implementation of
      the convention. This is an urgent question because seen realistically, it will
      not be possible to realize all rights at once and thus some rights need to
      receive greater priority than others. I will argue that the capabilities approach
      can be regarded as supporting the rights specified in the CRPD, but that it
      proves unable to guide the implementation process due to an insufficient
      grounding of the capabilities. Employing the capabilities approach thus leads to
      only limited results. 

PMID- 24446937
TI  - Human rights, civil rights: prescribing disability discrimination prevention in
      packaging essential health benefits.
AB  - This article explores rights-based approaches to protecting disabled people
      against inequities in access to health care services. Understanding health care
      as a human right, as is found in the UN Convention on the Rights of People with
      Disabilities (CRPD), fails to provide theoretical machinery for responding to
      certain pressing challenges. An alternative account, understanding health care as
      a civil right, proves more promising. This latter approach then is applied to the
      right to health care under the U.S. Affordable Care Act (ACA), which contains
      provisions that could be antithetical to, and thus fail to comply with, the
      nondiscrimination standard of meaningful access to health care benefits. 

PMID- 24446938
TI  - Supported decision-making and personal autonomy for persons with intellectual
      disabilities: article 12 of the UN convention on the rights of persons with
      disabilities.
AB  - Making decisions is an important component of everyday living, and issues
      surrounding autonomy and self-determination are crucial for persons with
      intellectual disabilities. Article 12 (Equal Recognition before the Law) of the
      UN Convention on the Rights of Persons with Disabilities addresses this issue of
      decision-making for persons with disabilities: the recognition of legal capacity.
      Legal capacity means recognizing the right to make decisions for oneself. Article
      12 is also moving in the direction of supported decision-making, as an
      alternative to substituted decision-making. The objective of this paper is to
      show conceptually the connection between supported decisionmaking and the
      preservation of personal autonomy for persons with intellectual disabilities.
      This paper discusses supported decision-making based on Bach and Kerzner's model:
      (a) legally independent status, (b) supported decision- making status, and (c)
      facilitated decision-making status. Arguments will be made based on John Stuart
      Mill's concept of autonomy and arguments against it using Sarah Conly's argument
      for paternalism. 

PMID- 24446939
TI  - Expanding the horizons of disability law in India: a study from a human rights
      perspective.
AB  - Disabled/"differently abled" persons by virtue of being human have the right to
      enjoy human rights to life, liberty, equality, security, and dignity. However,
      due to social indifference, psychological barriers, a limited definition of
      "disability" entitling protection of law, and a lack of proper data, disabled
      persons in India remain an invisible category. Although several laws exit to
      ensure their full and effective participation in society, they remain
      insufficient as they are primarily based on the government's discretion. At the
      same time, whenever the judiciary finds an opportunity, it acts as a real
      protector of disabled persons, but it is not feasible to knock on the door of the
      judiciary for every request. Interestingly, various civil societies and human
      rights activists have occasionally asserted the rights of the disabled. However,
      unless the foundation stones of law are fortified, disabled persons cannot fully
      realize their rights. It is high time to enact effective laws, with timely
      implementation, to protect their interests and empower their capabilities that
      are based on a "rights-based approach" rather than on the charity, medical, or
      social approaches. Thus, the horizons of law must be expanded to provide a "human
      friendly environment" for all of the disabled to overcome the barriers that
      impair their development. 

PMID- 24446940
TI  - Disability, "being unhealthy," and rights to health.
AB  - Often advocates for persons with disabilities strongly object to the claim that
      disability essentially involves a decrement in health. Yet, it is a mystery why
      anyone with an impairment would ever deny, or feel uncomfortable being told that,
      their impairment is at bottom a health problem. In this paper, I investigate the
      conceptual linkages between health and disability, relying on robust
      conceptualizations of both notions, and conclude it makes no conceptual sense to
      insist that a person can be seriously impaired yet still be, or become,
      "perfectly healthy." But that cannot be the end of it since this kind of error is
      commonly made, and I try to tease out the reason why not only disability
      advocates but agencies like the WHO and the CDC fall victim to it. I conclude by
      conceding that there are indeed sound political reasons for being cautious about
      the alignment of disability and ill-health, but suggest that the price we pay in
      conceptual confusion may be too high to allow those reasons to dictate policy. 

PMID- 24446941
TI  - Subversive subjects: rule-breaking and deception in clinical trials.
AB  - Research subjects do not always conform to research requirements. When their
      personal interests conflict with the demands of participation, some subjects
      surreptitiously break the rules. These subjects are subversive--they undermine
      the research endeavor. In rejecting the restrictions research imposes, subversive
      subjects diminish the value of research results. From one vantage point,
      subversive subjects engage in unethical behavior. They create risks to themselves
      and others; they also disregard ethical responsibilities to adhere to research
      agreements and tell the truth. At the same time, subversive subjects expose
      ethical problems in the design and conduct of clinical trials. Features of the
      research environment create fertile ground for subject subversion. Intensified
      policing and guidance are two common strategies for reducing subject subversion,
      but collaborative reforms are more consistent with the partnership model of
      clinical research.

PMID- 24446942
TI  - The ethics of intellectual property rights in an era of globalization.
AB  - Since the 1980s, developed countries, led by the United States and the countries
      of the European Union, have sought to incorporate intellectual property rights
      provisions into global trade agreements. These countries successfully negotiated
      the World Trade Organization's 1994 Agreement on Trade-Related Aspects of
      Intellectual Property Rights (TRIPS), which required developing countries to
      adopt intellectual property provisions comparable to developed countries. In this
      manuscript, we review the policy controversy surrounding TRIPS and examine the
      two main ethical arguments articulated in its support--a theory of natural rights
      and a utilitarian argument. We contend that these theories provide insufficient
      bases for an intellectual property rights regime that compromises access to
      essential medicines in the developing world. While the policy community has
      engaged in active debate around the policy effects of TRIPS, scholars have not
      thoroughly considered the full ethical underpinnings of those policy arguments.
      We believe that a more robust understanding of the ethical implications of the
      agreement should inform policy discussions in the future.

PMID- 24446943
TI  - Supporting second victims of patient safety events: shouldn't these
      communications be covered by legal privilege?
AB  - Adverse events that harm patients can also have a harmful impact on health care
      workers. A few health care organizations have begun to provide psychological
      support to these Second Victims, but there is uncertainty over whether these
      discussions are admissible as evidence in malpractice litigation or disciplinary
      proceedings. We examined the laws governing the admissibility of these
      communications in 5 states, and address how the laws might affect participation
      in programs designed to support health care workers involved in adverse events.
      We found that privilege is uneven from state-to-state, and also unclear.
      Ambiguity alone could have a chilling effect on Second Victim programs. We
      propose legislation to protect volunteer and health care worker communications
      provided by peer counselors, or failing this, updating of statutory provisions to
      explicitly include these communications within the ambit of existing protections.
      Enhancing protections could help to foster an environment of healing for both
      patients and caregivers.

PMID- 24446944
TI  - Another look at the legal and ethical consequences of pharmacological memory
      dampening: the case of sexual assault.
AB  - Research on the use of propranolol as a pharmacological memory dampening
      treatment for post-traumatic stress disorder is continuing and justifies a second
      look at the legal and ethical issues raised in the past. We summarize the general
      ethical and legal issues raised in the literature so far, and we select two for
      in-depth reconsideration. We address the concern that a traumatized witness may
      be less effective in a prosecution emerging from the traumatic event after memory
      dampening treatment. We analyze this issue in relation to sexual assault, where
      the suggestion that corroborating evidence may remedy any memory defects is less
      likely to be helpful. We also consider the clinical ethical question about a
      physician's obligation to discuss potential legal consequences of memory
      dampening treatment. We conclude that this latter question reflects a general
      problem related to novel medical treatments where the broader socio-legal
      consequences may be poorly understood, and suggest that issues of this sort could
      usefully be addressed through the promulgation of practice guidelines. 

PMID- 24446945
TI  - The right to language.
AB  - We argue for the existence of a state constitutional legal right to language. Our
      purpose here is to develop a legal framework for protecting the civil rights of
      the deaf child, with the ultimate goal of calling for legislation that requires
      all levels of government to fund programs for deaf children and their families to
      learn a fully accessible language: a sign language. 

PMID- 24446946
TI  - Adherence to the request criterion in jurisdictions where assisted dying is
      lawful? A review of the criteria and evidence in the Netherlands, Belgium,
      Oregon, and Switzerland.
AB  - Some form of assisted dying (voluntary euthanasia and/or assisted suicide) is
      lawful in the Netherlands, Belgium, Oregon, and Switzerland. In order to be
      lawful in these jurisdictions, a valid request must precede the provision of
      assistance to die. Non-adherence to the criteria for valid requests for assisted
      dying may be a trigger for civil and/or criminal liability, as well as
      disciplinary sanctions where the assistor is a medical professional. In this
      article, we review the criteria and evidence in respect of requests for assisted
      dying in the Netherlands, Belgium, Oregon, and Switzerland, with the aim of
      establishing whether individuals who receive assisted dying do so on the basis of
      valid requests. We conclude that the evidence suggests that individuals who
      receive assisted dying in the four jurisdictions examined do so on the basis of
      valid requests and third parties who assist death do not act unlawfully. However,
      further research on the elements that may undermine the validity of requests for
      assisted dying is warranted. More research on the reasons why requests for
      assisted dying are refused is also desirable. 

PMID- 24446947
TI  - Predictive genetic testing of children and the role of the best interest
      standard.
AB  - The "best interest standard" is the guidance principle for pediatric healthcare
      in the United States (US) and the United Kingdom (UK). In the UK, the best
      interest standard may also be used as an intervention principle when parents make
      good but non-ideal decisions whereas intervention in the US requires a
      determination of abuse or neglect. I examine whether and how the different uses
      of the best interest standard influence predictive genetic testing of children. 

PMID- 24446948
TI  - A place for all at the global health table: a case study about creating an
      interprofessional global health project.
AB  - This essay is a reflection on the "why" and "how" of creating an
      interprofessional global health project, with specific focus on the challenges of
      incorporating law students into this type of educational activity. 

PMID- 24446951
TI  - High precision fabrication and positioning of nanoelectrodes in a nanopore.
AB  - A simple and versatile method for the direct fabrication of tunneling electrodes
      with controllable gap distance by using electron-beam-induced deposition (EBID)
      is presented. We show that tunneling nanogaps smaller than the minimum feature
      size realizable by conventional EBID can be achieved with a standard scanning
      electron microscope. These gaps can easily be embedded in nanopores with high
      accuracy. The controllability of this fabrication method and the nanogap geometry
      was verified by SEM and TEM imaging. Furthermore, tunneling spectroscopy in a
      group of solvents with different barrier heights was used to determine the
      nanogap functionality. Ultimately, the presented fabrication method can be
      further applied for the fabrication of arrays of nanogap/nanopores or nanogap
      electrodes with tunable electrode materials. Additionally, this method can also
      offer direct fabrication of nanoscale electrode systems with tunable spacing for
      redox cycling and plasmonic applications, which represents an important step in
      the development of tunneling nanopore structures and in enhancing the
      capabilities of nanopore sensors. 

PMID- 24446953
TI  - Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults:
      a phase III randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE: Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A
      ligand currently being investigated for the treatment of epilepsy. The purpose of
      this phase III study was to evaluate the efficacy and safety/tolerability of
      adjunctive BRV in adults with uncontrolled partial-onset (focal) seizures.
      METHODS: This was a prospective, multicenter, randomized, double-blind, placebo
      controlled, parallel-group, fixed-dose trial (N01253; NCT00464269). Adults aged
      16-70 years with well-characterized partial epilepsy not fully controlled despite
      treatment with one or two antiepileptic drugs (AEDs) were enrolled. Patients who
      experienced eight or more partial-onset seizures, whether or not secondarily
      generalized, during the 8-week prospective baseline period were randomized
      (1:1:1:1) to receive twice-daily placebo (PBO) or BRV (5, 20, or 50 mg/day)
      without titration. The primary efficacy endpoint was percent reduction over PBO
      in baseline-adjusted partial-onset seizure frequency/week during the 12-week
      treatment period. Comparison of BRV with PBO was sequential (50, 20 mg/day, then
      5 mg/day). Secondary endpoints included >=50% responder rate and median percent
      reduction from baseline in partial-onset seizure frequency/week. Post hoc
      analyses included the primary efficacy endpoint evaluated over 28 days and
      exploratory subanalyses of efficacy by seizure subtype. Safety and tolerability
      assessments included treatment-emergent adverse events (TEAEs), laboratory tests,
      electrocardiography, vital signs, and physical and neurologic examinations. KEY
      FINDINGS: Of 400 patients randomized, 396 were included in the intent-to-treat
      (ITT) population (PBO n = 98, BRV 5 mg/day n = 97, BRV 20 mg/day n = 100, BRV 50
      mg/day n = 101) and 392 comprised the modified ITT (mITT) population. A total of
      361 (91.2%) of 396 patients completed the study. Most patients (78.3%) were
      receiving two concomitant AEDs. Percent reduction in partial-onset seizure
      frequency/week over PBO was -0.9% (p = 0.885) for BRV 5 mg/day, 4.1% (p = 0.492)
      for BRV 20 mg/day, and 12.8% (p = 0.025) for BRV 50 mg/day (mITT population).
      Statistical significance was also achieved for the percent reduction over PBO in
      baseline-adjusted partial-onset seizure frequency/28 days for BRV 50 mg/day
      (22.0%; p = 0.004) but not for the other BRV dose groups. In the BRV 50 mg/day
      group, statistical significance was also seen for the >=50% responder rate (BRV
      32.7% vs. PBO 16.7%; p = 0.008) and median percent reduction from baseline in
      partial-onset seizure frequency/week (BRV 30.5% vs. PBO 17.8%; p = 0.003). In the
      exploratory subanalysis by seizure subtype, median percent reduction from
      baseline in seizure frequency/week and >=50% responder rate were numerically
      greater than PBO in the BRV 20 and 50 mg/day groups for simple partial, complex
      partial, and secondarily generalized seizures. BRV was generally well tolerated,
      with the majority of TEAEs being mild-to-moderate in intensity. Of the TEAEs
      reported by >=5% patients, those with a frequency >3% higher than PBO for any
      dose of BRV compared with PBO were somnolence, dizziness, fatigue, influenza,
      insomnia, nasopharyngitis, vomiting, diarrhea, urinary tract infection, and
      nausea. SIGNIFICANCE: Adjunctive BRV at a daily dose of 50 mg was associated with
      statistically significant reductions in seizure frequency compared with PBO. All
      doses of BRV showed good tolerability throughout the study.

PMID- 24446952
TI  - Cyclooxygenase-2 in epilepsy.
AB  - Epilepsy is one of the more prevalent neurologic disorders in the world,
      affecting approximately 50 million people of different ages and backgrounds.
      Epileptic seizures propagating through both lobes of the forebrain can have
      permanent debilitating effects on a patient's cognitive and somatosensory brain
      functions. Epilepsy, defined by the sporadic occurrence of spontaneous recurrent
      seizures (SRS), is often accompanied by inflammation of the brain. Pronounced
      increases in the expression of key inflammatory mediators (e.g., interleukin 
      1beta [IL-1beta], tumor necrosis factor alpha [TNFalpha], cyclooxygenase-2 [COX
      2], and C-X-C motif chemokine 10 [CXCL10]) after seizures may cause secondary
      damage in the brain and increase the likelihood of repetitive seizures. The COX-2
      enzyme is induced rapidly during seizures. The increased level of COX-2 in
      specific areas of the epileptic brain can help to identify regions of seizure
      induced brain inflammation. A good deal of effort has been expended to determine
      whether COX-2 inhibition might be neuroprotective and represent an adjunct
      therapeutic strategy along with antiepileptic drugs used to treat epilepsy.
      However, the effectiveness of COX-2 inhibitors on epilepsy animal models appears
      to depend on the timing of administration. With all of the effort placed on
      making use of COX-2 inhibitors as therapeutic agents for the treatment of
      epilepsy, inflammation, and neurodegenerative diseases there has yet to be a
      selective and potent COX-2 inhibitor that has shown a clear therapeutic outcome
      with acceptable side effects.

PMID- 24446954
TI  - Treatment of infantile spasms with very high dose prednisolone before high dose
      adrenocorticotropic hormone.
AB  - PURPOSE: This study investigated the short-term response to a standardized
      hormonal therapy protocol for treatment of infantile spasms. METHODS: Twenty
      seven children with video electroencephalography (EEG)-confirmed infantile spasms
      received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2
      weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was
      ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks
      and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day)
      intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks.
      Response was again determined by overnight video-EEG after ACTH therapy. KEY
      FINDINGS: Sixty-three percent (17/27) of patients responded completely to
      prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a
      complete response after an additional 2-week course with ACTH. Among 27 subjects
      with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12%
      (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a
      relapse between 2 and 9 months after initial response. SIGNIFICANCE: Very high
      dose prednisolone demonstrated significantly higher efficacy than previously
      reported for lower doses in prior studies. High dose ACTH may be superior to very
      high dose prednisolone, and in lieu of a definitive clinical trial, the choice
      between prednisolone and ACTH for initial treatment of infantile spasms remains
      controversial.

PMID- 24446955
TI  - Brief group psychoeducation for psychogenic nonepileptic seizures: a neurologist
      initiated program in an epilepsy center.
AB  - OBJECTIVE: To evaluate therapeutic efficacy upon augmenting the initial
      communication to patients regarding the diagnosis of psychogenic nonepileptic
      seizures (PNES) with a novel, brief group psychoeducation administered by the
      same team that provided the video-electroencephalography (VEEG) confirmed
      diagnosis and within 4 weeks of the diagnosis. METHODS: Prior to discharge from
      the epilepsy monitoring unit (EMU), a standardized communication strategy was
      utilized to explain the diagnosis of PNES to all patients prior to enrollment.
      Enrolled patients were then randomized to either participation in three
      successive and monthly group psychoeducational sessions (intervention group), or
      routine seizure clinic follow-up visits (control group). Both groups completed
      questionnaires at time of enrollment, and then at approximately 3 months (follow
      up 1) and 6 months (follow-up 2) after discharge, assessing for: (1) primary
      outcomes that include a measure of psychosocial functioning, as well as interval
      difference in seizure frequency/intensity; and (2) secondary outcomes that
      include interval seizure-related emergency room visits or hospitalizations,
      development of new and medically unexplained symptoms, and results of an internal
      measure of knowledge and perception outcomes. RESULTS: The majority (73%) of
      patients from the intervention group commenced on therapy sessions within 4 weeks
      after learning of the diagnosis. Although we did not observe significant group
      difference in seizure frequency/intensity, patients from the intervention group
      showed significant improvement on the Work and Social Adjustment Scale (WSAS)
      scores at both follow-up 1 (p = 0.013) and follow-up 2 (p = 0.038) after
      discharge from the EMU. In addition, we observed a trend toward lesser likelihood
      for seizure-related emergency room visits or hospitalizations for the
      intervention group (p = 0.184), as well as meaningful insights from an internal
      measure of intervention outcomes. SIGNIFICANCE: These findings suggest that our
      cost/resource effective, brief group psychoeducational program, when administered
      early and by the same team who confirmed and communicated the diagnosis of PNES,
      may contribute to significant functional improvement among participating
      patients.

PMID- 24446957
TI  - A meta-analysis of complications of subdural electrode placement.

PMID- 24446958
TI  - In response to comments on Adverse events related to extraoperative invasive EEG
      monitoring with subdural grid electrodes: a systematic review and meta-analysis.

PMID- 24446959
TI  - Parietal seizures mimicking psychogenic nonepileptic seizures.

PMID- 24446960
TI  - In response to comments on Parietal seizures mimicking psychogenic nonepileptic
      seizures.

PMID- 24446961
TI  - Combined effect of three types of biophysical stimuli for bone regeneration.
AB  - Pretreatment using various types of biophysical stimuli could provide appropriate
      potential to cells during construction of the engineered tissue in vitro. We
      hypothesized that multiple combinations of these biophysical stimuli could
      enhance osteogenic differentiation in vitro and bone formation in vivo. Cyclic
      strain, an electromagnetic field, and ultrasound were selected and combined as
      effective stimuli for osteogenic differentiation using a developed bioreactor.
      Here we report the experimental evaluation of the osteogenic effects of various
      combinations of three different biophysical stimuli in vitro and in vivo using
      human adipose-derived stem cells (ASCs). Osteogenic differentiation of ASCs was
      accelerated by multiple-combination biophysical stimulation in vitro. However,
      both single stimulation and double-combination stimulation were sufficient to
      accelerate bone regeneration in vivo, while the osteogenic marker expression of
      those groups was not as high as that of triple-combination stimulation in vitro.
      We inferred from these data that ASCs appropriately differentiated into the
      osteogenic lineage by biophysical stimulation could be a better option for
      accelerating bone formation in vivo than relatively undifferentiated or
      completely differentiated ASCs. Although many questions remain about the
      mechanisms of combined effects of various biophysical stimuli, this approach
      could be a more powerful tool for bone tissue regeneration. 

PMID- 24446962
TI  - Fever survey highlights significant variations in how infants aged <=60 days are
      evaluated and underline the need for guidelines.
AB  - AIM: To assess the common practices for evaluating and treating febrile infants
      aged <=60 days in a nationwide survey. METHODS: Questionnaires were administrated
      to inpatient paediatric departments in all 25 hospitals in Israel. RESULTS: Of
      the 25 centres surveyed (100% response rate), only 36% had written protocols
      concerning the approach to young febrile infants. The existence of a written
      protocol was significantly associated with the level of medical centre (tertiary
      versus primary and secondary, p = 0.041) and with the number of local paediatric
      infectious disease specialists (p = 0.034). In 13 (52%) hospitals, a normal white
      blood cell count was defined as 5000-15 000 cells/mL and 20 (80%) centres use C
      reactive protein. Hospitalisation was mandatory in most (96%) centres for all
      neonates aged <=28 days. Low-risk infants aged 29-60 days were hospitalised in
      68.4% of the primary and secondary hospitals, compared with 33.3% tertiary
      centres. Ampicillin and gentamicin was the routine empiric antibiotic treatment
      for febrile infant in 92% of centres. CONCLUSION: Significant differences exist
      among centres in the evaluation of febrile infants aged <=60 days exist. These
      differences reflect the lack of, and highlight the need for, national or
      international guidelines for the evaluation of fever in this age group.

PMID- 24446964
TI  - In situ live observation of nucleation and dissolution of sodium chlorate
      nanoparticles by transmission electron microscopy.
AB  - The formation of crystals from solution requires the initial self-assembly of
      units of matter into stable periodic structures reaching a critical size. The
      early stages of this process , called nucleation, are very difficult to
      visualize. Here we describe a novel method that allows real time observation of
      the dynamics of nucleation and dissolution of sodium chlorate clusters in an
      ionic liquid solution using in situ transmission electron microscopy. Using ionic
      liquids as solvent circumvents the problem of evaporation and charging, while the
      nucleation frequency was reduced by using saturated solutions. We observe
      simultaneous formation and dissolution of prenucleation clusters, suggesting that
      high-density fluctuations leading to solid cluster formation exist even under
      equilibrium conditions. In situ electron diffraction patterns reveal the
      simultaneous formation of crystalline nuclei of two polymorphic structures, the
      stable cubic phase and the metastable monoclinic phase, during the earliest
      stages of nucleation. These results demonstrate that molecules in solution can
      form clusters of different polymorphic phases independently of their respective
      solubility. 

PMID- 24446963
TI  - A reduction in Ptprq associated with specific features of the deafness phenotype
      of the miR-96 mutant mouse diminuendo.
AB  - miR-96 is a microRNA, a non-coding RNA gene which regulates a wide array of
      downstream genes. The miR-96 mouse mutant diminuendo exhibits deafness and
      arrested hair cell functional and morphological differentiation. We have
      previously shown that several genes are markedly downregulated in the diminuendo
      organ of Corti; one of these is Ptprq, a gene known to be important for
      maturation and maintenance of hair cells. In order to study the contribution that
      downregulation of Ptprq makes to the diminuendo phenotype, we carried out
      microarrays, scanning electron microscopy and single hair cell electrophysiology
      to compare diminuendo mutants (heterozygous and homozygous) with mice homozygous
      for a functional null allele of Ptprq. In terms of both morphology and
      electrophysiology, the auditory phenotype of mice lacking Ptprq resembles that of
      diminuendo heterozygotes, while diminuendo homozygotes are more severely
      affected. A comparison of transcriptomes indicates there is a broad similarity
      between diminuendo homozygotes and Ptprq-null mice. The reduction in Ptprq
      observed in diminuendo mice appears to be a major contributor to the
      morphological, transcriptional and electrophysiological phenotype, but does not
      account for the complete diminuendo phenotype. 

PMID- 24446965
TI  - An unusual swollen dermal lesion in a 14-month-old child.
AB  - A 14-month-old child was brought to the pediatric emergency unit in the morning,
      after his parents discovered inflammatory lesion on his left thigh. Three hours
      later, he was admitted to our unit, his vital signs were normal and his physical
      examination revealed a round swollen lesion of 7-8 cm in diameter with blisters
      on the surface and an additional inflammatory reaction of his left thigh ( Figs.
      1 and 2 ). The parental interview provides the cause. The child was discharged
      after the lesion was dressed and a follow-up scheduled.

PMID- 24446967
TI  - Review of acute chemical incidents as a first step in evaluating the usefulness
      of physiologically based pharmacokinetic models in such incidents.
AB  - CONTEXT. Acute chemical incidents can have substantial public health consequences
      in terms of morbidity and mortality. OBJECTIVE. We aimed to characterize acute
      chemical incidents and near-misses in the Netherlands and compare the results
      with previous studies. This review is a first step in evaluating whether
      Physiologically Based Pharmacokinetic (PBPK) models can be of value in acute
      chemical incidents. MATERIAL AND METHODS. Government, regional, municipal and
      University Hospital Institutes involved in the management of acute chemical
      incidents in the Netherlands were contacted, and they provided data between 2008
      and 2010 on the characteristics and consequences of the incidents. The study is a
      retrospective epidemiological study based on data from five institutes. Incidents
      involving biological agents or radiation were excluded. RESULTS. A total of 764
      reports were available which involved 722 incidents after cross-matching the
      different sources of data. Forty incidents were excluded, leaving 682 incidents
      for which information was available in accordance with the inclusion criteria. Of
      the 682 incidents included in this study, most occurred in non-industrial
      buildings (37%) or industrial sites (34%). The most frequently observed event
      types were loss of containment (60%) and fire (36%), leading to gas emission
      (54%), followed by spill of liquid or solid chemicals (36%). The chemicals
      involved were most often products of combustion (e.g. smoke, soot, particles,
      25%) and volatile organic compounds (e.g. solvents, styrene, xylene, 23%),
      followed by inorganic gases (e.g. carbon monoxide, hydrogen, hydrogen sulphide,
      13%). A minimum of 847 people experienced adverse health effects following
      exposure during a chemical incident, and 10 fatalities were reported. The most
      frequently reported symptoms were respiratory (27%), due to irritant chemicals.
      The number of incidents related to fire and the number of injured people were
      higher in this study than in previous studies; 49% of the injured were
      transported to hospital. DISCUSSION. This study helps to identify which chemicals
      are frequently involved in acute chemical incidents in the Netherlands. The
      results will be used in future to assess whether PBPK models may be useful for
      risk assessment of chemicals often involved in acute chemical incidents and for
      which human toxicological and kinetic data are scarce.

PMID- 24446968
TI  - Change in methadone syrups needs to consider different aspects.

PMID- 24446969
TI  - IFN-gamma release assay conversions and reversions. Challenges with serial
      testing in U.S. health care workers.
AB  - RATIONALE: IFN-gamma release assays (IGRAs) including the QuantiFERON-TB gold in
      tube test (QFT-GIT) are increasingly used in place of the tuberculin skin test
      (TST) in surveillance programs for Mycobacterium tuberculosis infection in the
      United States. However, data on conversions, reversions, and predictive value of
      QFT in such programs for health care workers (HCWs) are limited. OBJECTIVES: The
      purpose of this study is to assess long-term reproducibility and conversion and
      reversion rates of QFT-GIT among HCWs who underwent serial testing at a tertiary
      care center in the United States. METHODS: Retrospective chart review of HCWs at
      the Central Arkansas Veterans Healthcare System (CAVHS) who underwent serial
      testing with QFT-GIT as a part of their employee screening between November 1,
      2008 and January 31, 2011. MEASUREMENTS AND MAIN RESULTS: A total of 2,303 HCWs
      had at least 2 QFT-GITs 1 year apart. The initial QFT-GIT was positive for 69 and
      2 were indeterminate. Of these 69 HCWs, 31 (45%) reverted on repeat testing, and
      25 of 31 (80.6%) HCWs who reverted had a negative look-back TST. Of the 2,232
      HCWs with an initial negative QFT-GIT, 71 (3.2%) converted on repeat testing. A
      third QFT-GIT assay was performed in 41 of the 71 converters and 90% (37 of 41)
      reverted back to negative. Only two HCWs had TST and QFT-GIT conversion.
      CONCLUSIONS: Poor IGRA reproducibility and a low predictive value of QFT-GIT
      conversions indicate that QFT-GIT with current interpretation criteria should not
      be used for serial screening of U.S. HCWs. Negative TSTs have higher
      reproducibility than QFT-GIT for serial testing of HCWs in low tuberculosis
      incidence settings.

PMID- 24446970
TI  - An insight into the skin penetration enhancement mechanism of N
      methylpyrrolidone.
AB  - This work aims to elucidate the mechanism by which N-methylpyrrolidone (NMP)
      enhances the skin permeation of a compound by combining experimental data with
      molecular dynamic (MD) simulations. The addition of 10% NMP significantly
      increased the propranolol (PR) permeation through the human epidermis (~ 15
      MUg/cm(2) vs ~ 30 MUg/cm(2)) while resulting inefficacious on hydrocortisone (HC)
      diffusion. No significant alterations in the stratum corneum structure were found
      after the in vitro treatment of human epidermis with NMP dispersed in mineral oil
      or water by attenuated total reflectance Fourier transform infrared (ATR-FTIR)
      analyses. MD simulations revealed the formation of a complex by H-bonds and the
      pi-pi stacking interactions between the NMP's amido group and the drug's aromatic
      systems. The size of the depicted NMP/PR clusters was in line with the
      hydrodynamic radius derived by dynamic light scattering analyses (~ 2.00 nm).
      Conversely, no interaction, and consequently cluster formation, between NMP and
      HC occurred. These results suggest that NMP is effective in enhancing the drug
      permeation through human epidermis by a cotransport mechanism when NMP/drug
      interaction occurs.

PMID- 24446971
TI  - Evaluation of aortopexy in the management of severe tracheomalacia after
      esophageal atresia repair.
AB  - Severe tracheomalacia (TM) is a difficult problem in esophageal atresia (EA)
      patients. We reviewed our experience with aortopexy and other interventions for
      severe TM in this population. With review ethics board approval, a retrospective
      review of TM in postoperative EA patients was conducted (1989-2010).
      Demographics, perinatal, and surgical information regarding EA repair was
      collected. TM infants were analyzed for symptomatology, clinical severity,
      investigations, interventions, and outcomes. Data are presented as proportions or
      median(range). One hundred and thirty-two EA patients were reviewed. Most had
      type C atresia (87.3%), and 18 patients (13.6%) died. Twenty-five patients
      (18.9%) had TM of whom five (20%) died. Median symptom onset was 18 days (0-729)
      after EA repair, with stridor (64%) or retractions/distress (44%) being most
      frequent. Four and two patients had airway obstruction or cardiorespiratory
      arrest, respectively. Median time from symptom onset to investigations was 11
      days; these were most commonly rigid bronchoscopy (56%) and fluoroscopy (36%).
      Ten patients (40%) had severe TM on bronchoscopy. Six underwent aortopexy, one
      fundoplication, and three were treated medically. Length of hospital stay (LOS)
      post-aortopexy was 13 days (5-60), and ventilation time was 2 days (0-9). LOS was
      60.5 (1-69) days postdiagnosis in non-aortopexy patients. Readmission rates for
      respiratory issues were significantly less in the aortopexy (median 0 vs. 5; P =
      0.048) group over 2-year follow up after discharge. Complications of aortopexy
      included transfusion (1) and temporary diaphragmatic paresis (1), and one
      mortality secondary to severe congenital cardiac anomalies. Our experience
      suggests that aortopexy is safe and effective for the treatment of severe TM. It
      is associated with reduced LOS compared with other treatment strategies and few
      complications or long-term sequelae.

PMID- 24446972
TI  - Homoisoflavanone prevents mast cell activation and allergic responses by
      inhibition of Syk signaling pathway.
AB  - BACKGROUND: Mast cells play important roles in allergic inflammatory responses
      because they produce leukotrienes (LTs), prostaglandins (PGs), and a variety of
      inflammatory cytokines. Thus, pharmacological interventions for allergies have
      focused on inhibiting mast cell activation. Homoisoflavanone (HIF), isolated from
      Cremastra appendiculata Makino, has anti-angiogenic activities; however, its
      effects on allergic reactions have not been determined. The aim of this study was
      to assess the inhibitory effects of HIF on mast cell activation, which is
      critical for anti-allergic reaction and the underlying mechanisms. METHODS:
      Enzyme-linked immunosorbent assays, quantitative real-time PCR, western blot
      analyses, and degranulation assay were performed to measure pro-inflammatory and
      allergic mediators in PMA/A23187- or IgE/antigen-stimulated mouse bone marrow
      derived mast cells (BMMCs), HMC-1, RBL-1, or human PBMC-derived mast cells
      treated with or without HIF. The anti-allergic effects of HIF were determined in
      mouse models using dinitrophenol-immunoglobulin E-induced passive cutaneous
      anaphylaxis (PCA) and compound 48/80-induced ear swelling. RESULTS:
      Homoisoflavanone down-regulated PGD2 , LTB4 , and LTC4 production and inhibited
      the production of pro-inflammatory cytokines, such as interleukin-6 and tumor
      necrosis factor-alpha in PMA/A23187- or IgE/antigen-stimulated mast cells. The
      molecular mechanisms by which HIF caused these inhibitory effects were determined
      to be the inactivation of spleen tyrosine kinase (Syk) signaling and the
      concurrent suppression of cPLA2 . HIF inhibited IgE-mediated PCA and compound
      48/80-induced ear swelling in mouse. CONCLUSIONS: Homoisoflavanone inhibited mast
      cell activation through the suppression of Syk pathway together with the
      inhibition of cPLA2 . Thus, it might be a good candidate molecule for allergic
      diseases.

PMID- 24446973
TI  - The life course, care pathways and elements of vulnerability. A picture of health
      needs in a vulnerable population.
AB  - OBJECTIVE: This paper presents a contextual approach to the assessment of dental
      health needs based on a life course approach with vulnerability integrated within
      the assessment of need. BACKGROUND: Life course approaches to needs
      assessment,health care planning and commissioning of services are gaining
      popularity as there is a move away from simpler assessments of need based purely
      on population demographics such as age. The use of an assessment of vulnerability
      will be essential in the development of care pathways that are based on patient
      and population need rather than demand. METHODS: As an example of the health
      needs of a vulnerable population data are presented on an oral health needs
      assessment within nursing and residential homes in the North West of England.
      FINDINGS: These data serve to demonstrate the challenges of the disease burden
      within such a population but also the complexities of commissioning and
      delivering services to this group of patients. CONCLUSIONS: Care pathways
      designed to assist such patients should consider not only prevention and
      treatment modalities but also the means of implementing such therapies in varying
      settings and utilising the whole dental team.

PMID- 24446974
TI  - Epidemiology of oral health conditions in older people.
AB  - The main conditions of interest when considering the epidemiology of oral
      diseases among older people are tooth loss, dental caries, periodontitis, dry
      mouth and oral pre-cancer/cancer, along with oral-health-related quality of life
      (OHRQoL). This article presents an overview of what is known about the
      epidemiology of each of the main conditions of interest among older populations. 

PMID- 24446975
TI  - Poor oral health, a potential new geriatric syndrome.
AB  - This article presents a brief introduction to the medical aspects of ageing and
      age-related diseases, and to some geriatric syndromes, followed by a discussion
      on their impact on general and oral healthcare provision to community-dwelling
      older people. Recent investigations suggest that inflammation constitutes a
      biological foundation of ageing and the onset of age-related diseases.
      Multimorbidity and polypharmacy, together with alterations in pharmacokinetics
      and pharmacodynamics, make older people at risk of adverse medication reactions.
      A side effect of several medications is causing xerostomia and hyposalivation,
      and both the type and number of medications used are relevant. New options of
      general healthcare provision to community-dwelling older people are the use of
      mobility aids and assistive technology devices, domiciliary health care, respite
      care and telecare. Their oral health status may be jeopardised by frailty,
      disability, care dependency and limited access to professional oral health care.
      Recommendations for improvement are the following: better integrating oral health
      care into general health care, developing and implementing an oral healthcare
      guideline, providing customised oral hygiene care aids, domiciliary oral
      healthcare provision, visiting dental hygienists and/or nurses, oral hygiene
      telecare, easily and safely accessible dental offices, transforming dentistry
      into medical oral health care and upgrading dentists to oral physicians. In case
      oral healthcare providers do not take the responsibility of persuading society of
      the importance of adequate oral health, weakened oral health of community
      dwelling older people will become a potential new geriatric syndrome. 

PMID- 24446976
TI  - Developing pathways for oral care in elders: challenges in care for the dentate
      the subject?
AB  - OBJECTIVE: This paper reviews potential age-associated risk factors for
      satisfactory oral function and oral disease to inform the development of care
      pathways for the older person. BACKGROUND: Alterations in dental status or both
      physical and biological change associated with age can impact on oral disease and
      oral function. MATERIALS AND METHODS: Older people tend to have fewer teeth and
      some are edentulous. Physical and biological changes in bodily function with age
      can also affect oral health care either directly or indirectly. RESULTS:
      Reductions in chewing ability impact on the foods people choose to eat because of
      perceived difficulty with chewing, with a potentially deleterious affect on
      dietary quality. This is worse in people with xerostomia where chewing and
      swallowing are impaired anyway. Change in the cell-mediated inflammatory response
      impacts on gingival and periodontal disease manifestation and progression.
      Sarcopenia makes the physical act of toothbrushing more challenging. Caries
      remains a clinical problem that affects both the crowns and the roots of teeth.
      Coronal lesions tend to be around existing restorations where there is no
      evidence base about care/prevention. CONCLUSION: The physical and clinical
      changes that occur with ageing require an altered pattern of care for older
      people which is adjusted to their disease risk and encourage diversity of foods
      consumption.

PMID- 24446977
TI  - Developing pathways for oral care in elders: evidence-based interventions for
      dental caries prevention in dentate elders.
AB  - BACKGROUND: Dental caries is becoming an ever-growing challenge as the number of
      elders maintaining their teeth increases. There is a need for low-cost, effective
      preventive interventions to retain natural teeth for elders. OBJECTIVE: The
      purpose of this article is to evaluate evidence based interventions for dentate
      elders, specifically the adjunct therapies of fluoride, chlorhexidine, xylitol,
      casein phosphopeptide-amorphous calcium phosphate, ozone, and herbal liquorice.
      RESULTS: Fluoride interventions have demonstrated prevention and remineralization
      of dental caries in elders. Systematic reviews of the literature are unable to
      establish definitive conclusions regarding the effectiveness of other adjunct
      therapies in dental caries prevention. CONCLUSIONS: Further research with elders
      requires improved study design with well designed multi-center trials.
      Considerations for new strategies for research of the effectiveness of therapies
      to reduce dental caries include the development and evaluation of combinations of
      therapeutic interventions and dental caries management by risk assessment.

PMID- 24446978
TI  - Confronting dental uncertainty in old age.
AB  - OBJECTIVE: To provide an overview of the literature about uncertainty in health
      care and how it relates to the oral health care of older people. BACKGROUND: The
      medical literature describes uncertainty in health care from the initial informed
      consent to its impact on a patient's ability to cope with undesirable outcomes.
      METHODS: A narrative review of the medical, dental and psychological literature
      was conducted to identify pertinent information on the theory and implications of
      uncertainty in healthcare. The findings are infused into a case-report
      illustrating the recurrence of uncertainty experienced by an older woman who had
      multiple treatments over several years to restore her dentition damaged severely
      by dental caries. RESULTS: Uncertainty originates from inadequate understanding,
      incomplete information and undifferentiated alternatives leading to unnecessary
      diagnostic tests and healthcare costs. A conceptual taxonomy clarifies the
      characteristics of uncertainty in the context of scientific, practical or
      personal sources and offers management possibilities through effective
      communications to identify choices and probabilities that help patients to adapt
      and cope with adverse events. CONCLUSIONS: Uncertainty pervades healthcare. It
      can lead patients to self-blame, anger and withdrawal from care unless it is
      communicated effectively so that they can adapt and cope with the disappointment
      of adversity and continue with alternative approaches to care.

PMID- 24446979
TI  - Interventions for edentate elders--what is the evidence?
AB  - Demographic developments indicate an increasing proportion of elderly persons in
      the population as well as longer life expectancies. Furthermore, the prevalence
      of edentulism is decreasing, and natural teeth are being retained until later in
      life. Geriatric patients are more frequently fragile with multiple co
      morbidities, including frequent medication-related side effects such as
      xerostomia. Cognitive impairment also increases with age and presents a
      considerable challenge to oral hygiene and dental treatment. Edentulous patients
      present a particular challenge, as muscle skill and the ability to adapt to a new
      denture diminish with age. Duplication techniques reduce the adaptation of
      replacement dentures, and implants are increasingly used to stabilise lower
      complete dentures, significantly improving chewing efficiency and preventing peri
      implant bone loss. Implant overdentures may reverse some of the functional,
      psychological and psychosocial effects of tooth loss and thus increase the oral
      health-related quality of life until late in life. Evidence from RCTs exists on
      the 10-year survival of implants and implant overdentures, but few studies have
      investigated the problems and survival rates when the patient loses autonomy. The
      standard of care in geriatric patients has to be adapted to the patient's
      motivation, functional and cognitive impairment, and medical condition as well as
      his/her socio-economic context. 

PMID- 24446980
TI  - Developing care pathways--lessons from the Steele Review implementation in
      England.
AB  - OBJECTIVE: This paper sets out to discuss the concept of care pathways, review
      their definition, features and implementation and using an example from the NHS
      dental system in England guide the development of an elder care pathway.
      BACKGROUND: Care pathways have developed from quality management approaches in
      industry and focus on a number of steps which are intended to lead to expected
      outcomes. The existing definition and descriptors of care pathways serve well,
      but miss the complex process underlying the development of pathways, their
      structure, implementation and evaluation. FINDINGS: The literature identifies key
      features of clinical pathways and from the developing field of implementation
      science, the factors likely to support pathway implementation. Pathways must be
      generic enough to enable them to be applicable broadly, but specific enough for
      them to be locally relevant and population specific. The development of care
      pathways in the National Health Service (NHS) Dental Service in England is
      described and when compared with the implementation science literature exhibits
      features identified as positive factors for implementation. As a result a
      contribution to the pathway definition literature is offered. CONCLUSIONS:
      Learning from the literature and the practical experience described from England,
      the process for developing dental care pathways for dependent elders should begin
      with the creation of a high level pathway, which is cognisant of the clinical and
      implementation science evidence base.

PMID- 24446981
TI  - Delivering the evidence--skill mix and education for elder care.
AB  - OBJECTIVES: To review the current status of dental curricula on elder care, and
      the current curricula regarding elder care, and it's effect on altering
      practitioner behaviors while addressing the needs of a growing North American
      elder population. BACKGROUND: An impending crisis is looming over the oral
      healthcare of our aging population. At the same moment that life expectancy is
      being extended through increasingly complex healthcare improvements, the numbers
      of trained dental providers capable and interested in delivering the needed care
      is failing to grow at an adequate rate. DISCUSSION: The skills necessary to
      manage these increasingly complex patients require an interprofessional approach
      capable of delivering care to sicker patients, in a variety of living
      accommodations, while managing a variety of care givers. The dental skills
      necessary to treat these elderly are modifications of skills students routinely
      learn in dental school. As a matter of fact, the skills students acquire to treat
      an adult patient population may be contrary to the basic skills necessary to
      manage the elderly dependent adult patient. Teaching students the nuance
      differences needed to properly diagnose and care for this population is a
      difficult task that must be taught in a contextual environment. CONCLUSION:
      Significant changes in the teaching of dental management of the elderly are
      critical within much of the education community. Just as teaching students to
      care for the pediatric population as general dentists, the clinical education
      must involve a sufficient number of quality experiences to address issues of both
      competency, that of the graduate to perform care independently, and attitudes,
      the actually willingness to treat the elderly.

PMID- 24446982
TI  - The elderly as a market--challenges to evidence.
AB  - OBJECTIVE: To review the role of the oral care industry in the oral health of
      elders and opportunities for partnership with other key stakeholders. BACKGROUND:
      The elder population is growing at a faster rate than any other segment of the
      population. This is coupled with a greater probability of maintaining the
      dentition into later life and an increase in complex restorative work. If an
      elder's situation changes, they are highly vulnerable to a rapid onset of oral
      disease that can be devastating and extremely difficult to address. MATERIALS AND
      METHODS: This manuscript reviews the role of the oral care industry in
      understanding this population as a market and the different approaches that might
      be used in promoting health. RESULTS: Two key market segments were identified,
      the vulnerable elders with high levels of chronic oral disease, systemic
      complications, medications and often inability to maintain good standards of oral
      hygiene and a wealthier, health and beauty conscious group with a keen interest
      in maintaining a healthy, aesthetically pleasing and functional dentition
      throughout their lives. CONCLUSIONS: It is likely that within current healthcare
      models, the oral care of elders will be unsustainable, with a smaller working
      population funding ever-increasing health care needs. 'Home care' combined with
      effective professional preventive and effective therapeutic options are
      essential. Partnerships between the oral care industry and oral care providers,
      to deliver education and engagement of care workers, medical practitioners,
      pharmacists and social services, are essential over the next few decades.

PMID- 24446983
TI  - Cultural challenges to oral healthcare implementation in elders.
AB  - For successful implementation of oral healthcare services for elders, there is a
      need to understand and respond to their oral health beliefs, perceived needs and
      preferred type of care services, all of which are shaped by their cultural
      beliefs and values. This poses challenges to oral healthcare providers,
      especially when serving a diverse elderly population with people coming from
      different cultural backgrounds. The general principles of oral healthcare
      provision and their adaptation to serve culturally diverse elderly populations
      are discussed. The oral health beliefs and behaviours of Chinese, an ethnic group
      that can be found in many countries across the world, are highlighted and used as
      examples. Chinese elders generally attach a higher value to the physical
      functions than to the appearance of their dentition and prefer to use traditional
      self-care methods to deal with their oral health problems rather than to seek
      professional services. There is need to incorporate into the training of oral
      healthcare providers the competence to adapt their services to the beliefs and
      practices of culturally diverse elderly population groups in different settings. 

PMID- 24446984
TI  - The Seattle Care Pathway for securing oral health in older patients.
AB  - There is a need for a structured, evidence based approach to care for older
      dental patients. The following article describes the development of the Seattle
      Care Pathway based upon a workshop held in 2013. An overview is provided on the
      key issues of older persons dental care including the demography shift, the
      concept of frailty, the need for effective prevention and treatment to be linked
      to levels of dependency and the need for a varied and well educated work force.
      The pathway is presented in tabular form and further illustrated by the examples
      in the form of clinical scenarios. The pathway is an evidence based, pragmatic
      approach to care designed to be globally applicable but flexible enough to be
      adapted for local needs and circumstances. Research will be required to evaluate
      the pathways application to this important group of patients.

PMID- 24446985
TI  - Workshop as a tribute to Asuman Kiyak.

PMID- 24446986
TI  - The unique manuka effect: why New Zealand manuka honey fails the AOAC 998.12 C-4
      sugar method.
AB  - Conversion of dihydroxyacteone (DHA) to methylglyoxal (MGO) has been shown to be
      the key mechanism for the growth in "apparent" C-4 sugar content in nonperoxide
      activity (NPA) manuka honey. This reaction is enhanced by heating and storage
      time and is demonstrated for the first time in clover honey adulterated with DHA
      purchased from a chemical supplier and in manuka honey containing naturally
      occurring DHA and MGO. After heating at 37  degrees C for 83 days, pure clover
      honey with no added DHA has the same apparent C-4 sugar content as at t = 0 days.
      The same clover honey adulterated with synthetic DHA added at t = 0 days and
      heated at 37  degrees C over the same time scale shows a change in apparent C-4
      sugars from 2.8 to 5.0%. Four NPA manuka honeys heated over longer periods show
      an increase in apparent C-4 sugars of up to 280% after 241 days. This study
      strongly suggests that a protein fractionation effect occurs in the conversion of
      DHA to MGO in higher NPA manuka honey, rendering the remaining delta(13)C protein
      value more negative and falsely indicating C-4 sugar addition when using the AOAC
      998.12 method. 

PMID- 24446987
TI  - Poly(ethylene glycol)-modified PAMAM-Fe3O4-doxorubicin triads with the potential
      for improved therapeutic efficacy: generation-dependent increased drug loading
      and retention at neutral pH and increased release at acidic pH.
AB  - Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles are a promising
      drug-delivery system that can enhance the therapeutic effects of chemotherapy
      drugs, such as doxorubicin (DOX), with minimized side effects. This work explores
      the optimization of the potential therapeutic efficiency of PAMAM-Fe3O4-DOX
      triads. Different generations (G3, G5, and G6) of PAMAMs were synthesized and
      modified with poly(ethylene glycol) (PEG) and then used to encapsulate glutamic
      acid-modified Fe3O4 nanoparticles. The Fe3O4-dendrimer carriers (Fe3O4-DGx where
      x = the generation 3, 5, or 6 of dendrimers) were electrostatically conjugated
      with drug DOX. The loading and releasing efficiencies of DOX increased with the
      PAMAM generation from 3 to 6. The loading efficiencies of DOX molecules were 87,
      93, and 96% for generations 3, 5, and 6, respectively. At pH 5, the DOX release
      efficiencies within 24 h were approximately 60, 68, and 80% for generations 3, 5,
      and 6, respectively. At pH 7.4, the DOX releasing efficiency was as low as ~ 15%.
      Compared to the negative control, the PAMAM-Fe3O4-DOX triads showed only mild
      toxicity against human cervical adenocarcinoma cell line HeLa at pH 7.4, which
      indicated that DOX can be fairly benignly carried and sparingly released until
      PAMAM-Fe3O4-DOX is taken up into the cell.

PMID- 24446988
TI  - Sample entropy-based analysis of differential and traditional training effects on
      dynamic balance in healthy people.
AB  - The authors applied algorithms based on the sample entropy (SampEn) measurements
      to analyze the evolution of regularity in center of pressure displacements on the
      medialateral (ML) and anteroposterior (AP) axes after the application of 2
      balance training methods: differential and traditional. A total of 14 young
      healthy participants took part in this study undertaking 5 SampEn measurements, a
      pre- and posttest, and 3 retests on dynamic balance and monopodal support.
      Results show a SampEn increase in the ML axis over the medium term (4 weeks) with
      both training methods. Over the short term (1 week), only traditional training
      shows a SampEn increase in the ML axis. In the AP axis, the traditional training
      method also shows a SampEn increase over the medium and short terms. A higher
      irregularity of the COP displacements is also present in the same axis, far from
      the higher regularity observed in the AP axis. These findings suggest a
      variability strategy related with the postural control during supports.

PMID- 24446991
TI  - Potential of medicinal plants as antimicrobial and antioxidant agents in food
      industry: a hypothesis.
AB  - Many food preservation strategies can be used for the control of microbial
      spoilage and oxidation; however, these quality problems are not yet controlled
      adequately. Although synthetic antimicrobial and antioxidant agents are approved
      in many countries, the use of natural safe and effective preservatives is a
      demand of food consumers and producers. This paper proposes medicinal plants,
      traditionally used to treat health disorders and prevent diseases, as a source of
      bioactive compounds having food additive properties. Medicinal plants are rich in
      terpenes and phenolic compounds that present antimicrobial and antioxidant
      properties; in addition, the literature revealed that these bioactive compounds
      extracted from other plants have been effective in food systems. In this context,
      the present hypothesis paper states that bioactive molecules extracted from
      medicinal plants can be used as antimicrobial and antioxidant additives in the
      food industry. 

PMID- 24446992
TI  - Weight of the Nation - moving forward, reversing the trend: editorial note.

PMID- 24446993
TI  - Obesity prevention in the early care and education setting: successful
      initiatives across a spectrum of opportunities.
AB  - With an estimated 12.1% of children aged 2-5 years already obese, prevention
      efforts must target our youngest children. One of the best places to reach young
      children for such efforts is the early care and education setting (ECE). More
      than 11 million U.S. children spend an average of 30 hours per week in ECE
      facilities. Increased attention at the national, state, and community level on
      the ECE setting for early obesity prevention efforts has sparked a range of
      innovative efforts. To assist these efforts, CDC developed a technical assistance
      and training framework - the Spectrum of Opportunities for Obesity Prevention in
      the ECE setting - which also served as the organizing framework for the Weight of
      the Nation ECE track. Participants highlighted their efforts at national, state,
      and local levels pursuing opportunities on the Spectrum, the standards and best
      practices that had been the emphasis of their efforts, and common steps for
      developing, implementing, and evaluating initiatives. Strong leadership and
      collaboration among a broad group of stakeholders; systematic assessment of
      needs, opportunities and resources; funding sources; and training and
      professional development were reported to be integral for successful
      implementation of standards and best practices, and sustainability. 

PMID- 24446994
TI  - Improving the Weight of the Nation by engaging the medical setting in obesity
      prevention and control.
AB  - This manuscript highlights examples of strategies that have made strides in
      improving the quality of health care environments, systems-level improvements to
      support self-management, and collaborations between primary care and public
      health to support effective approaches to prevent obesity among children and
      adults in the U.S. 

PMID- 24446995
TI  - Preventing obesity through schools.
AB  - This paper describes highlights from the Weight of the Nation 2012 Schools Track.
      Included is a summary of 16 presentations. Presenters shared key actions for
      obesity prevention through schools. The information provided at the Weight of the
      Nation can help school health practitioners access tools, apply evidence-based
      strategies, and model real-world examples to successfully start obesity
      prevention initiatives in their jurisdiction. 

PMID- 24446996
TI  - The role of community, state, territorial, and tribal public health in obesity
      prevention.
AB  - This article explores how governmental public health authorities can contribute
      to public health efforts to address obesity by monitoring the prevalence of
      obesity and associated risk factors, investigating the contributing factors,
      informing the public, and working with the citizens in their jurisdiction to
      develop solutions that fit the needs and sensibilities of the people. 

PMID- 24446997
TI  - Workplace health: engaging business leaders to combat obesity.
AB  - This article explores how employers can be part of the solution to obesity by
      offering workplace wellness programs and facilitating opportunities for physical
      activity, access to healthier foods and beverages, and incentives for disease
      management and prevention to help prevent weight gain among their employees. 

PMID- 24446998
TI  - Built environment and physical activity promotion: place-based obesity prevention
      strategies.
AB  - This paper seeks to encourage continued innovation in translating built
      environment and transportation-focused physical activity research into practice.
      Successful strategies, policies, and tools from across the U.S. and globally that
      demonstrate potential for wider-scale implementation are highlighted. The
      importance of building practice and translational research partnerships with
      groups and organizations outside traditional public health spheres, such as those
      who work in real estate and land-use development, is also discussed. 

PMID- 24446999
TI  - The food and water system: impacts on obesity.
AB  - The Weight of the NationTM (WON) conference was held in Washington, D.C. This
      article presents the issues and topics presented and discussed within the Food
      and Water System: Agriculture, Access and Sustainability track. Areas for
      opportunity are outlined in this article. 

PMID- 24447000
TI  - Beyond the code book: legal tools for accelerating progress in obesity
      prevention.
AB  - This paper highlights methods - other than legislative and regulatory directives 
      through which decision-makers may use law and the legal system to facilitate the
      systems-wide change that the IOM calls for. 

PMID- 24447002
TI  - Efficacy of alcohol interventions for first-year college students: a meta
      analytic review of randomized controlled trials.
AB  - OBJECTIVE: Alcohol use established during the first-year of college can result in
      adverse consequences during the college years and beyond. In this meta-analysis,
      we evaluated the efficacy of interventions to prevent alcohol misuse by first
      year college students. METHOD: Studies were included if the study reported an
      individual- or group-level intervention using a randomized controlled trial,
      targeted 1st-year college students, and assessed alcohol use. Forty-one studies
      with 62 separate interventions (N = 24,294; 57% women; 77% White) were included.
      Independent raters coded sample, design, methodological features, and
      intervention content. Weighted mean effect sizes, using fixed- and random-effects
      models, were calculated. Potential moderators, determined a priori, were examined
      to explain variability in effect sizes. RESULTS: Relative to controls, students
      receiving an intervention reported lower quantity and frequency of drinking and
      fewer problems (d(+)s = 0.07-0.14). These results were more pronounced when the
      interventions were compared with an assessment-only control group (d(+)s = 0.11
      0.19). Intervention content (e.g., personalized feedback) moderated the efficacy
      of the intervention. CONCLUSIONS: Behavioral interventions for 1st-year college
      students reduce alcohol consumption and alcohol-related problems. Interventions
      that include personalized feedback, moderation strategies, expectancy challenge,
      identification of risky situations, and goal-setting optimize efficacy.
      Strategies to prevent alcohol misuse among first-year students are recommended.

PMID- 24447003
TI  - Therapeutic alliance in face-to-face and telephone-administered cognitive
      behavioral therapy.
AB  - OBJECTIVE: Telephone-administered therapies have emerged as an alternative method
      of delivery for the treatment of depression, yet concerns persist that the use of
      the telephone may have a deleterious effect on therapeutic alliance. The purpose
      of this study was to compare therapeutic alliance in clients receiving cognitive
      behavioral therapy (CBT) for depression by telephone (T-CBT) or face-to-face (FtF
      CBT). METHOD: We randomized 325 participants to receive 18 sessions of T-CBT or
      FtF-CBT. The Working Alliance Inventory (WAI) was administered at Weeks 4 and 14.
      Depression was measured during treatment and over 1 year posttreatment follow-up
      using the Hamilton Rating Scale for Depression and Patient Health Questionnaire
      9. RESULTS: There were no significant differences in client or therapist WAI
      between T-CBT or FtF-CBT (Cohen's f2 ranged from 0 to .013, all ps > .05). All
      WAI scores predicted depression end of treatment outcomes (Cohen's f2 ranged from
      .009 to .06, all ps < .02). The relationship between the WAI and depression
      outcomes did not vary by treatment group (Cohen's f2 ranged from 0 to .004, ps >
      .07). The WAI did not significantly predict depression during posttreatment
      follow-up (all ps > .12). CONCLUSIONS: Results from this analysis do not support
      the hypothesis that the use of the telephone to provide CBT reduces therapeutic
      alliance relative to FtF-CBT.

PMID- 24447004
TI  - Patterns of early change and their relationship to outcome and early treatment
      termination in patients with panic disorder.
AB  - OBJECTIVE: Recently, innovative statistical tools have been used to model
      patterns of change in psychological treatments. These tools can detect patterns
      of change in patient progress early in treatment and allow for the prediction of
      treatment outcomes and treatment length. METHOD: We used growth mixture modeling
      to identify different latent classes of early change in patients with panic
      disorder (N = 326) who underwent a manualized cognitive-behavioral treatment.
      RESULTS: Four latent subgroups were identified, showing clusters of change
      trajectories over the first 5 sessions. One of the subgroups consisted of
      patients whose symptoms rapidly decreased and also showed the best outcomes. This
      information improved treatment prediction by 16.1% over patient intake
      characteristics. Early change patterns also significantly predicted patients'
      early treatment termination. Patient intake characteristics that significantly
      predicted class membership included functional impairment and separation anxiety.
      CONCLUSIONS: These findings suggest that early treatment changes are uniquely
      predictive of treatment outcome.

PMID- 24447005
TI  - Pathways from teacher depression and child-care quality to child behavioral
      problems.
AB  - OBJECTIVE: The purpose of this study was to examine the associations among
      teacher depression, global child-care quality, and child internalizing and
      externalizing behavioral problems in early child-care settings. METHOD: We
      analyzed data from 3-year-old children (N = 761) and their mothers, primarily of
      disadvantaged socioeconomic status in urban areas, in the late 1990s using the
      Fragile Families and Child Wellbeing Study. We also had data from the children's
      teachers, who reported their own depressed moods. Child behavioral problems were
      reported by both teachers and parents, and global environmental quality of child
      care was observed. Path analysis tested direct and indirect effects of teacher
      depression on children's behavioral problems via global child-care quality.
      RESULTS: Teacher depression was directly and indirectly linked to teacher
      reported externalizing and internalizing problems through observed global child
      care quality, whereas for parent-reported outcomes, teacher depression was only
      directly related to children's internalizing problems. CONCLUSIONS: Results of
      this study suggest that teachers' depressive symptoms can be a contributor to
      global environmental child-care quality and to child externalizing and
      internalizing behavioral problems. Practical implications are that programs and
      policies must take into account effects of teacher depression on child-care
      quality and young children's school readiness regarding behavioral problems.
      Future research should further explore these relationships.

PMID- 24447007
TI  - A 10-year randomized controlled trial of the Early Risers conduct problems
      preventive intervention: effects on externalizing and internalizing in late high
      school.
AB  - OBJECTIVE: The purpose of this study was to examine the long-term effects of the
      Early Risers "Skills for Success" Conduct Problems Prevention Program (ER;
      August, Bloomquist, Realmuto, & Hektner, 2007), a multifaceted program targeting
      social, emotional, behavioral, and academic risk and protective factors to
      promote adaptive psychological development. METHOD: Based on the random
      assignment of their school, 245 kindergartners (mean age = 6.6 years, SD = 0.57;
      68.6% male) with elevated teacher-rated aggressive behavior either participated
      in ER for 3 intensive years plus 2 booster years or served as controls.
      Participants were assessed annually during the intervention with teacher and
      parent reports and at 2 follow-up points. In the current study, 129 of the
      original participants were reassessed with diagnostic interviews in late high
      school (mean age = 16.3, SD = 0.52), and multiple imputation was used to deal
      appropriately with missing data. RESULTS: Program participants had significantly
      fewer symptoms of conduct disorder, oppositional defiant disorder, and major
      depressive disorder than did controls. The program's effect on increasing social
      skills and parent discipline effectiveness by Grade 3 mediated these effects.
      CONCLUSIONS: The results of this study provide further evidence of the long-term
      positive effects of multicomponent, elementary-age, targeted conduct problems
      prevention programs. Training children in social skills and parents in effective
      discipline are possible mechanisms to divert maladaptive developmental cascades.

PMID- 24447008
TI  - The "trust" heuristic: arguments from authority in public health.
AB  - The work of public health depends on a relationship of trust between health
      workers and members of the public. This relationship is one in which the public
      must trust the advice of health experts, even if that advice is not always
      readily understood or judged to be agreeable. However, it will be argued in this
      article that the pact of trust between public health workers and members of the
      public has been steadily eroded over many years. The reasons for this erosion are
      examined as are attempts to characterize the concept of trust in empirical
      studies. The discussion then considers how a so-called informal fallacy, known as
      the "argument from authority," might contribute to attempts to understand the
      trust relationship between the public and health experts. Specifically, this
      argument enables the lay person to bridge gaps in knowledge and arrive at
      judgements about public health problems by attending to certain logical and
      epistemic features of expertise. The extent to which lay people are able to
      discern these features is considered by examining the results of a study of
      public health reasoning in 879 members of the public. 

PMID- 24447006
TI  - Effect of cognitive-behavioral therapy for anxiety disorders on quality of life:
      a meta-analysis.
AB  - OBJECTIVE: Although cognitive-behavioral therapy (CBT) is effective for treating
      anxiety disorders, little is known about its effect on quality of life. To
      conduct a meta-analysis of CBT for anxiety disorders on quality of life, we
      searched for relevant studies in PubMed, PsycINFO, and the Cochrane Library and
      conducted manual searches. METHOD: The search identified 44 studies that included
      59 CBT trials, totaling 3,326 participants receiving CBT for anxiety disorders.
      We estimated the controlled and within-group random effects of the treatment
      changes on quality of life. RESULTS: The pre-post within-group and controlled
      effect sizes were moderately strong (Hedges's g = 0.54 and Hedges's g = 0.56,
      respectively). Improvements were greater for physical and psychological domains
      of quality of life than for environmental and social domains. The overall effect
      sizes decreased with publication year and increased with treatment duration. Face
      to-face treatments delivered individually and in groups produced significantly
      higher effect sizes than Internet-delivered treatments. CONCLUSION: CBT for
      anxiety disorders is moderately effective for improving quality of life,
      especially in physical and psychological domains. Internet-delivered treatments
      are less effective than face-to-face treatments in improving quality of life.

PMID- 24447011
TI  - Effect of antioxidant extract from cherries on diabetes.
AB  - Diabetes is a chronic metabolic disorder in humans constituting a major health
      concern today whose prevalence has continuously increased worldwide over the past
      few decades. Production of reactive oxygen species (ROS) and disturbed capacity
      of antioxidant defense in diabetic subjects have been reported. It has been
      suggested that enhanced production of free radicals and oxidative stress is the
      central event for the development of diabetic complications. Antioxidants can
      play an important role in the improvement of diabetes. There are many reports on
      the effects of antioxidants in the management of diabetes. This study aimed at
      evaluating the effect of antioxidant extract and purified sweet and sour Cherries
      on hyperglycemia, microalbumin and creatinine level in alloxan-induced diabetic
      rats. Thirty six adult Male Wistar rats were divided equally into six groups.
      Diabetes was induced in the rats by an intraperitoneal injection with 120 mg/kg
      body weight of alloxan. Oral administration of cherry extract at a concentration
      of 200 mg/kg body weight for 30 days significantly reduced the levels of blood
      glucose, and urinary microalbumin. Also an increase in the creatinine secretion
      level in urine was observed in the diabetic rats treated with the cherry extract
      as compared to untreated diabetic rats. In this paper, the most recent patent on
      the identification and treatment of diabetes is used. In conclusion, cherry
      antioxidant extract proved to have a beneficial effect on the diabetic rats in
      this study. In light of these advantageous results, it is advisable to broaden
      the scale of use of sweet and sour cherries extract in a trial to alleviate the
      adverse effects of diabetes. 

PMID- 24447012
TI  - Enhanced charge transfer kinetics of CdSe quantum dot-sensitized solar cell by
      inorganic ligand exchange treatments.
AB  - Enhancement of the charge transfer rate in CdSe quantum dot (QD) sensitized solar
      cells is one of the most important criteria determining cell efficiency. We
      report a novel strategy for enhancing charge transfer by exchanging the native,
      long organic chain to an atomic ligand, S(2-), with a simple solid exchange
      process. S(2-)-ligand exchange is easily executed by dipping the CdSe QDs
      sensitized photoanode into a formamide solution of K2S. The results show that
      this exchange process leads to an enhancement of the electronic coupling between
      CdSe QD and TiO2 by removing the insulating organic barrier to charge transfer,
      while maintaining its quantum confined band structure. This treatment
      significantly increases the charge transfer rate at the interfacial region
      between CdSe QDs and TiO2 as well as between the CdSe QDs and Red/Ox coupling
      electrolyte, as verified by time-resolved photoluminescence and electrochemical
      impedance spectroscopy measurements. Finally, the S(2-)-treated photoanode
      exhibits a much higher photovoltaic performance than the conventional MPA or TGA
      capped CdSe QDs sensitized solar cell. The findings reported herein propose an
      innovative route toward harvesting energy from solar light by enhancing the
      carrier charge transfer rate. 

PMID- 24447013
TI  - Analysis of continuous glucose monitoring data to assess outpatient closed-loop
      studies: considerations for different sensors.

PMID- 24447015
TI  - State policies and practices in behavior supports for persons with intellectual
      and developmental disabilities in the United States: a national survey.
AB  - Providing effective behavioral supports to decrease challenging behavior and
      replace it with appropriate alternative skills is essential to meeting the needs
      of many individuals with intellectual and developmental disabilities (IDD). It is
      also necessary for fulfilling the requirements of Medicaid-funded individual
      support plans and is important for moral, ethical, and societal reasons.
      Unfortunately, there is no national standard for behavioral support practices or
      source of information on the status of behavior support policies, practices, and
      services for adults with IDD at either state or national levels. The collection
      of comprehensive data on state behavior support definitions, provider
      qualifications, training, and oversight requirements is a necessary starting
      point for the development of plans to address needed policy and practice changes.
      This survey is the first national assessment of state policies and practices
      regarding the definition and delivery of behavior support services to people with
      intellectual and developmental disabilities receiving publicly financed supports
      in the United States.

PMID- 24447017
TI  - Effectiveness of responsive teaching with children with Down syndrome.
AB  - A randomized control study was conducted to evaluate Responsive Teaching (RT)
      with a sample of 15 Turkish preschool-aged children with Down syndrome (DS) and
      their mothers over a six-month period of time. RT is an early intervention
      curriculum that attempts to promote children's development by encouraging parents
      to engage in highly responsive interactions with them. Subjects were randomly
      assigned to treatment conditions: the control group consisted of standard
      preschool classroom services; the RT group received bi-weekly RT parent-child
      sessions in addition to standard services. RT mothers made significantly greater
      increases in their Responsiveness and Affect as wellas decreases in Directiveness
      than control group mothers. There were also significant group differences in
      children's interactive engagement and development. Children in the RT group
      improved their developmental quotient scores by an average of 47% compared to 7%
      for children in the control group. Results are described in terms of the effects
      of parental responsive interaction on the developmental functioning of children
      with DS.

PMID- 24447016
TI  - Receiving the initial Down syndrome diagnosis: a comparison of prenatal and
      postnatal parent group experiences.
AB  - This study explored the preliminary experiences of parents upon learning of their
      child's diagnosis of Down syndrome. Qualitative data from a web-based, national
      survey were analyzed based on two groups: prenatal (n  =  46) or postnatal (n  = 
      115) diagnosis. Three primary categories emerged from the data analysis: prenatal
      screening/testing decisions by parents, the adjustment process for parents, and
      postdiagnosis resources and support for parents. Participants' rationale behind
      pursuing testing ranged from wanting to be better prepared to not pursuing
      testing because it was not a factor in continuing the pregnancy. Participant
      reactions to the diagnosis involved a range of intense preliminary emotions;
      participants described their extreme grief and loss experience at the initial
      news of the diagnosis, which also was ambiguous in nature and required differing
      timelines of adjustment. Finally, participants described experiences with medical
      professionals, information/education, and faith/religion as resources and areas
      of support, although not all were described as positive in nature. Participants
      in both groups identified having negative experiences with medical professionals
      during the diagnosis process. The results indicated the importance of these early
      experiences for parents of children with Down syndrome and emphasize providing
      effective education, resources, and practical information from reliable sources.

PMID- 24447018
TI  - Management, leadership, and user control in self-advocacy: an english case study.
AB  - This paper presents findings from a qualitative research project on an English
      self-advocacy organization. In light of recent political and economic
      developments that have threatened the sustainability of a number of self-advocacy
      groups for people with intellectual disability, I seek to explore how one
      particular organization managed to survive and grow. In particular, the paper
      explores themes of management, leadership, and user control, linking these to
      external perceptions about self-advocacy organizations. The organization in my
      study developed an "interdependent" governance model based on key organizational
      roles for nondisabled advisors and self-advocates, which proved popular with
      external funders. Despite the organization's notable achievements, its success
      raises questions for the wider self-advocacy movement, notably how leadership
      capacity can be developed among self-advocates.

PMID- 24447019
TI  - Reciprocity and social capital in sibling relationships of people with
      disabilities.
AB  - Sibling relationships are some of the longest-lasting relationships people
      experience, providing ample opportunities to build connections across the life
      span. For siblings and people with intellectual and developmental disabilities
      (IDD), these connections take on an increased significance as their families age
      and parents can no longer provide care. This article presents findings from a
      qualitative study that addresses the question, "How do siblings support each
      other after parents no longer can provide care to the person with IDD?" Findings
      in this study suggest that siblings with and without disabilities experience
      reciprocity as a transitive exchange, which occurs through the creation of social
      capital in their families and community, and that nondisabled siblings mobilize
      their social capital to provide support to their sibling after parents pass away.
      Implications for future research as well as policy and practice are discussed.

PMID- 24447020
TI  - A social-ecological analysis of the self-determination literature.
AB  - This paper uses a social-ecological lens to examine self-determination research,
      attempting to organize what is known (and unknown) about contextual factors that
      have the potential to impact the development and expression of self-determined
      behavior in people with disabilities across multiple ecological systems.
      Identifying and categorizing the contextual factors that researchers suggest
      influence self-determination have the potential to allow for the development of a
      framework that promotes systematic consideration of contextual factors when
      designing, implementing, and evaluating supports to promote self-determination.
      Directions for future research and practice are discussed.

PMID- 24447021
TI  - Presidential address 2013-race to catch the future.

PMID- 24447024
TI  - Clinical and muscle biopsy findings in Norwegian paediatric patients with limb
      girdle muscular dystrophy 2I.
AB  - AIM: To describe patients diagnosed with limb girdle muscular dystrophy 2I
      (LGMD2I) in our paediatric departments between 2004 and 2012. METHODS: The
      hospital charts of 17 patients presenting for evaluation at a mean age of 7.8
      years (range 1-13 years) were retrospectively reviewed. RESULTS: With one
      exception, all patients were homozygous for the common mutation c.826C>A in the
      FKRP gene. Three patients experienced transient pronounced weakness as toddlers.
      Fatigue and muscle pain were most prominent, weakness less so, in children
      presenting at an older age. The degree of severity varied substantially. In
      certain cases, increased creatine kinase was an incidental finding. All walked
      independently by 18 months. When last evaluated at a mean age of 14.3 years
      (range 3.5-18 years), five patients were part-time wheelchair users. One patient
      was then treated for a cardiomyopathy. Creatine kinase was consistently
      increased, except presymptomatic in one patient. Muscle biopsies showed focal
      acute and chronic myopathic changes and pathological expression of alpha
      dystroglycan. No consistent relationship between clinical function and the degree
      of morphological pathology was found. CONCLUSION: LGMD2I is a relevant
      differential diagnosis when creatine kinase is increased in children presenting
      with fatigue, muscle pain and sometimes weakness.

PMID- 24447025
TI  - The pH in the microenvironment of human mesenchymal stem cells is a critical
      factor for optimal osteogenesis in tissue-engineered constructs.
AB  - The present study aimed at elucidating the effect of local pH in the
      extracellular microenvironment of tissue-engineered (TE) constructs on bone cell
      functions pertinent to new tissue formation. To this aim, we evaluated the
      osteogenicity process associated with bone constructs prepared from human Bone
      marrow-derived mesenchymal stem cells (hBMSC) combined with 45S5 bioactive glass
      (BG), a material that induces alkalinization of the external medium. The pH
      measured in cell-containing BG constructs was around 8.0, that is, 0.5 U more
      alkaline than that in two other cell-containing materials
      (hydroxyapatite/tricalcium phosphate [HA/TCP] and coral) constructs tested. When
      implanted ectopically in mice, there was no de novo bone tissue in the BG cell
      containing constructs, in contrast to results obtained with either HA/TCP or
      coral ceramics, which consistently promoted the formation of ectopic bone. In
      addition, the implanted 50:50 composites of both HA/TCP:BG and coral:BG
      constructs, which displayed a pH of around 7.8, promoted 20-30-fold less amount
      of bone tissue. Interestingly, hBMSC viability in BG constructs was not affected
      compared with the other two types of material constructs tested both in vitro and
      in vivo. Osteogenic differentiation (specifically, the alkaline phosphatase [ALP]
      activity and gene expression of RUNX2, ALP, and BSP) was not affected when hBMSC
      were maintained in moderate alkaline pH (<=7.90) external milieu in vitro, but
      was dramatically inhibited at higher pH values. The formation of mineralized
      nodules in the extracellular matrix of hBMSC was fully inhibited at alkaline
      (>7.54) pH values. Most importantly, there is a pH range (specifically, 7.9-8.27)
      at which hBMSC proliferation was not affected, but the osteogenic differentiation
      of these cells was inhibited. Altogether, these findings provided evidence that
      excessive alkalinization in the microenvironment of TE constructs (resulting, for
      example, from material degradation) affects adversely the osteogenic
      differentiation of osteoprogenitor cells. 

PMID- 24447026
TI  - Functional parcellation of the human primary somatosensory cortex to natural
      touch.
AB  - Despite the significance of human touch, brain responses to interpersonal manual
      touch have been rarely investigated. We used functional magnetic resonance
      imaging to study brain activity in eight healthy adults whose left hand was
      touched by two individuals, in separate runs and in 20-s blocks, either by
      holding, smoothing, or poking. Acceleration was measured from both the subject's
      and the touching person's hands for postimaging control of the stimuli.
      Independent component analysis of the functional magnetic resonance imaging data
      unraveled three functional networks involving the primary somatosensory cortex
      (SI). One network comprised the contralateral and another the ipsilateral
      Brodmann area 3. The third network included area 2 bilaterally, left-hemisphere
      middle temporal gyrus and dorsolateral prefrontal regions, ventral prefrontal
      cortices bilaterally, and middle cingulate cortex. The response shapes and
      polarities varied between the three networks. The contralateral area 3
      differentiated the responses between the three types of touch stimuli, and the
      response magnitudes depended on the variability of the touch within each block.
      However, the responses of the other two networks were strikingly similar to all
      stimuli. The subjects' reports on the pleasantness of the touch did not correlate
      with the characteristics of the SI responses. These findings imply area-specific
      processing of the natural human touch in three networks including the SI cortex,
      with only area 2 connected to a functional network of brain areas that may
      support social interaction. 

PMID- 24447027
TI  - Electronic chemical potentials of porous metal-organic frameworks.
AB  - The binding energy of an electron in a material is a fundamental characteristic,
      which determines a wealth of important chemical and physical properties. For
      metal-organic frameworks this quantity is hitherto unknown. We present a general
      approach for determining the vacuum level of porous metal-organic frameworks and
      apply it to obtain the first ionization energy for six prototype materials
      including zeolitic, covalent, and ionic frameworks. This approach for valence
      band alignment can explain observations relating to the electrochemical, optical,
      and electrical properties of porous frameworks. 

PMID- 24447028
TI  - Propofol administration is safe in adult eosinophilic esophagitis patients
      sensitized to egg, soy, or peanut.
AB  - BACKGROUND: Sedation might improve tolerability and adherence to endoscopic
      procedures in patients with eosinophilic esophagitis (EoE). Propofol
      administration is often contraindicated in patients with hypersensitivity to egg,
      soy, or peanut. OBJECTIVE: To investigate the safety of propofol administration
      for procedural sedation in EoE patients sensitized/allergic to egg, soy, peanut.
      METHODS: A retrospective observational study in adult EoE patients undergoing
      esophagogastroduodenoscopy with propofol sedation was conducted between January
      2009 and March 2013. Food-specific serum IgE and skin prick tests for egg, soy,
      peanut, and cross-reactant foods were performed in all patients. RESULTS: Sixty
      EoE adult patients, mostly on food elimination diets (91%), were evaluated (age:
      28 years (14-56), male gender (90%)). Atopy was present in 88% of patients, being
      the most prevalent comorbidities rhinoconjunctivitis (78%) and asthma (67%).
      Fifty-two patients (86%) were sensitized to either egg, soy, or peanut. Eighteen
      patients (28%) had a history of allergic reactions to egg, legumes, and nuts and
      strictly avoided these foods. A total of 404 upper endoscopies were performed
      under propofol sedation. No allergic adverse events were reported, except a
      transient bronchospasm after orotracheal intubation in an asthmatic adolescent
      receiving multiple drugs for anesthesia, in whom no sensitization to either
      propofol or its lipid vehicle was confirmed. CONCLUSIONS: Propofol was safely
      administered for procedural sedation in a large series of adult EoE patients
      multisensitized to egg, soy, peanut, showing one-third clinical allergy to these
      foods.

PMID- 24447029
TI  - Domain-specific self-efficacy is associated with measures of functional capacity
      and quality of life among patients with moderate to severe chronic obstructive
      pulmonary disease.
AB  - RATIONALE: The relationship between self-efficacy and health behaviors is well
      established. However, little is known about the relationship between self
      efficacy and health-related indicators among patients with chronic obstructive
      pulmonary disease (COPD). OBJECTIVES: The purpose of this cross-sectional cohort
      study was to test the hypothesis that the total score and specific subdomain
      scores of the COPD Self-Efficacy Scale (CSES) are associated with functional
      capacity and quality of life in a group of patients with moderate to severe COPD.
      METHODS: Relationships were examined in a cross-sectional study of baseline data
      collected as part of a randomized trial. Self-efficacy was measured using the
      five domains of the CSES: negative affect, emotional arousal, physical exertion,
      weather/environment, and behavioral. Measures of quality of life and functional
      capacity included SF-12: physical and mental composite scores, Chronic
      Respiratory Questionnaire dyspnea domain, and the 6-minute-walk test. Statistical
      analyses included Spearman correlation and categorical analyses of self-efficacy
      ("confident" vs. "not confident") using general linear models adjusting for
      potential confounders. MEASUREMENTS AND MAIN RESULTS: There were 325 patients
      enrolled with a mean age (standard deviation) of 68.5 (9.48) years, 49.5% male,
      and 91.69% non-Hispanic white. The negative affect, emotional arousal, and
      physical exertion domains were moderately correlated (range, 0.3-0.7) with the SF
      12 mental composite score and Chronic Respiratory Questionnaire dyspnea domain.
      In models exploring each CSES domain as "confident" versus "not confident" and
      adjusting for age, sex, race, pack-years, and airflow obstruction severity, there
      were multiple clinically and statistically significant associations between the
      negative affect, emotional arousal, and physical exertion domains with functional
      capacity and quality of life. CONCLUSIONS: The aggregated total CSES score was
      associated with better quality of life and functional capacity. Our analysis of
      subdomains revealed that the physical exertion, negative affect, and emotional
      arousal subdomains had the largest associations with functional capacity and
      quality of life indicators. These findings suggest that interventions to enhance
      self-efficacy may improve the functional capacity and quality of life of patients
      with moderate to severe COPD.

PMID- 24447030
TI  - Improved plant growth and Zn accumulation in grains of rice (Oryza sativa L.) by
      inoculation of endophytic microbes isolated from a Zn Hyperaccumulator, Sedum
      alfredii H.
AB  - This study is to investigate the possibility of zinc (Zn) biofortification in the
      grains of rice (Oryza sativa L.) by inoculation of endophytic strains isolated
      from a Zn hyperaccumulator, Sedum alfredii Hance. Five endophytic strains,
      Burkholderia sp. SaZR4, Burkholderia sp. SaMR10, Sphingomonas sp. SaMR12,
      Variovorax sp. SaNR1, and Enterobacter sp. SaCS20, isolated from S. alfredii,
      were inoculated in the roots of Japonica rice Nipponbare under hydroponic
      condition. Fluorescence images showed that endophytic strains successfully
      colonized rice roots after 72 h. Improved root morphology and plant growth of
      rice was observed after inoculation with endophytic strains especially SaMR12 and
      SaCS20. Under hydroponic conditions, endophytic inoculation with SaMR12 and
      SaCS20 increased Zn concentration by 44.4% and 51.1% in shoots, and by 73.6% and
      83.4% in roots, respectively. Under soil conditions, endophytic inoculation with
      SaMR12 and SaCS20 resulted in an increase of grain yields and elevated Zn
      concentrations by 20.3% and 21.9% in brown rice and by 13.7% and 11.2% in
      polished rice, respectively. After inoculation of SaMR12 and SaCS20, rhizosphere
      soils of rice plants contained higher concentration of DTPA-Zn by 10.4% and
      20.6%, respectively. In situ micro-X-ray fluorescence mapping of Zn confirmed the
      elevated Zn content in the rhizosphere zone of rice treated with SaMR12 as
      compared with the control. The above results suggested that endophytic microbes
      isolated from S. alfredii could successfully colonize rice roots, resulting in
      improved root morphology and plant growth, increased Zn bioavailability in
      rhizosphere soils, and elevated grain yields and Zn densities in grains. 

PMID- 24447032
TI  - Barriers to performing stretching exercises among Korean-Chinese female migrant
      workers in Korea.
AB  - OBJECTIVE: The purpose of this study was to investigate the barriers to
      performing stretching exercise experienced by Korean-Chinese female migrant
      workers during a community-based 12-week stretching exercise intervention trial.
      DESIGN AND SAMPLE: Qualitative secondary data analysis was conducted using
      telephone counseling interview transcripts from 27 middle-aged, Korean-Chinese
      migrant women workers. MEASURES: A semistructured interview question asking
      barriers to performing stretching exercise was given to women who did not adhere
      to recommended stretching exercise. During the 12-week home-based stretching
      exercise intervention trial, six telephone calls were made to participants
      biweekly to elicit barriers to performing stretching exercise. Directed content
      analysis approach was utilized using three barrier categories: intrapersonal,
      interpersonal, and work-related environmental factors based on the ecological
      model. RESULTS: Participants experienced an average of 2.5 barriers during the
      study period. Intrapersonal barriers included lack of time and lack of
      motivation, and interpersonal barriers included no family to provide support and
      also a feeling resistance from coworkers. Work-related environmental barriers
      included frequent job changes, long working hours, lack of rest time, and
      unpredictable job demands. CONCLUSIONS: The findings highlight that migrant
      workers in Korea face unique work-related difficulties which present barriers to
      exercise.

PMID- 24447033
TI  - Evaluation of attentional demands during motor learning: validity of a dual-task
      probe paradigm.
AB  - The aim of this study was to examine the validity of a 2-choice audio-vocal
      reaction time (RT) probe task for measuring the changes in attentional demand
      during practice and learning of a discrete motor task. Twenty participants
      practiced the motor task across 3 days and were probed with the RT task during
      either the preparation or execution phase of the primary task. As practice
      progressed, participants improved in the primary task performance and shortened
      the RTs to the probe task. This indicated that less attention was required to
      plan and execute the movement and suggested that the RT probe task was a
      sensitive and valid tool to measure changes in attentional demands across
      practice. The authors implemented several additional experimental controls to
      address possible confounders including unintentional learning of the probe task,
      primary-secondary task trade-off effects, and compliance with task priority
      instructions. These experimental controls further ensured the validity of the
      probe paradigm and interpretability of the dual-task cost findings. Our
      experimental methods provided confirmatory evidence for the validity of the 2
      choice RT task as a means to assess attentional demands during motor learning.

PMID- 24447031
TI  - Differences in paracingulate connectivity associated with epileptiform discharges
      and uncontrolled seizures in genetic generalized epilepsy.
AB  - OBJECTIVE: Patients with genetic generalized epilepsy (GGE) frequently continue
      to have seizures despite appropriate clinical management. GGE is associated with
      changes in the resting-state networks modulated by clinical factors such as
      duration of disease and response to treatment. However, the effect of generalized
      spike and wave discharges (GSWDs) and/or seizures on resting-state functional
      connectivity (RSFC) is not well understood. METHODS: We investigated the effects
      of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and
      seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation
      in simultaneous electroencephalography (EEG) and resting-state functional
      magnetic resonance imaging (fMRI) (EEG/fMRI) data from 72 GGE patients (23 with
      uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate
      cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes
      in cortical-subcortical resting-state networks and the default mode network
      (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible
      contamination of the resting state. RESULTS: (1) Higher frequency of GSWDs was
      associated with an increase in seed-based voxel correlation with cortical and
      subcortical brain regions associated with executive function, attention, and the
      DMN; (2) RSFC in patients with GGE, when compared to healthy controls, was
      increased between paracingulate cortex and anterior, but not posterior, thalamus;
      and (3) GGE patients with uncontrolled seizures exhibited decreased cerebellar
      RSFC. SIGNIFICANCE: Our findings in this large sample of patients with GGE (1)
      demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide
      evidence that different thalamic nuclei may be affected differently by GGE, and
      (3) suggest that cerebellum is a modulator of ictogenic circuits.

PMID- 24447036
TI  - Rated measures of narrative structure for written smoking-cessation texts.
AB  - This article describes the effect of a series of rated measures of narrative
      structure on recognition memory, agreement on story-relevant beliefs, and
      intention to engage in a health-related behavior-in this case smoking cessation.
      Using short smoking-cessation stories as stimuli, data were collected in a
      nationally representative sample of adult smokers (n = 1,312). Results suggested
      that messages rated as more sequential improved encoding and messages rated as
      containing more context decreased encoding. Messages rated high in transportation
      were associated with increased recognition, agreement with story-relevant
      beliefs, and intention to quit. Both positive and negative emotion were
      positively associated with intention to quit, but were negatively associated with
      recognition memory.

PMID- 24447037
TI  - Serum uric acid, the metabolic syndrome, and the risk of chronic kidney disease
      in patients with type 2 diabetes.
AB  - BACKGROUND: Serum uric acid (SUA) has been suggested as a potentially modifiable
      mediator associated with the metabolic syndrome. Hyperuricemia and metabolic
      syndrome were both associated with adverse renal outcome. However, epidemiologic
      data are limited regarding this relationship in patients with type 2 diabetes
      mellitus (T2DM). This study aims to determine whether elevated SUA is associated
      with an increased prevalence of metabolic risk factors, albuminuria, and chronic
      kidney disease (CKD) in a large sample of patients with T2DM. It also examines
      the combined effect of SUA and metabolic syndrome components on the odds of CKD.
      METHODS: A total of 1463 patients with T2DM were recruited. Blood samples were
      obtained to measure metabolic parameters. Patients with macroalbuminuria or an
      estimated glomerular filtration rate of <60 mL/min per 1.73 m(2) were considered
      as CKD cases. RESULTS: The prevalence of metabolic syndrome, central obesity,
      hypertension, high triglycerides (TGs), CKD, and macroalbuminuria was
      significantly higher in patients with hyperuricemia than those in the lowest
      tertile of SUA (T1). One standard deviation (SD) increment of SUA was
      significantly associated with metabolic syndrome, central obesity, and high TGs
      after adjustment for age, sex, estimated glomerular filtration rate (eGFR), and
      albuminuria. The odds of CKD went up to 1.37-fold with every 1 SD increment of
      SUA, independent of age, sex, and components of metabolic syndrome. There was a
      significant, graded increase in odds of CKD by increasing SUA levels and the
      number of metabolic syndrome risk factors (P<0.001). CONCLUSION: This study
      proposed a synergistic effect between SUA and metabolic syndrome components on
      the odds of CKD.

PMID- 24447039
TI  - Multiple pathways to identification: exploring the multidimensionality of
      academic identity formation in ethnic minority males.
AB  - Empirical trends denote the academic underachievement of ethnic minority males
      across various academic domains. Identity-based explanations for this persistent
      phenomenon describe ethnic minority males as disidentified with academics,
      alienated, and oppositional. The present work interrogates these theoretical
      explanations and empirically substantiates a multidimensional lens for discussing
      academic identity formation within 330 African American and Latino early
      adolescent males. Both hierarchical and iterative person-centered methods were
      utilized and reveal 5 distinct profiles derived from 6 dimensions of academic
      identity. These profiles predict self-reported classroom grades, mastery
      orientation, and self-handicapping in meaningful and varied ways. The results
      demonstrate multiple pathways to motivation and achievement, challenging previous
      oversimplified stereotypes of marginalized males. This exploratory study
      triangulates unique interpersonal and intrapersonal attributes for promoting
      healthy identity development and academic achievement among ethnic minority
      adolescent males.

PMID- 24447040
TI  - Promotion of oxygen reduction reaction durability of carbon-supported PtAu
      catalysts by surface segregation and TiO2 addition.
AB  - Highly effective carbon supported-Pt75Au25 catalysts for oxygen reduction
      reaction (ORR) are prepared though titanium dioxide modification and post heat
      treatment. After accelerated durability test (ADT) of 1700 cycles, the ORR
      activity of PtAu/C catalysts modified by TiO2 and air heat treatment is 3 times
      higher than that of the commercial Pt/C. The enhancement of ORR activity is
      attributed to surface and structural alteration by air-induced Pt surface
      segregation and lower unfilled d states. On the contrary, for TiO2 modified and
      H2 treated PtAu/C catalysts, the deterioration of the ORR activity may be due to
      the loss of electrochemical surface area after ADT and the increase of d-band
      vacancy. 

PMID- 24447041
TI  - Is graphene a promising nano-material for promoting surface modification of
      implants or scaffold materials in bone tissue engineering?
AB  - Bone tissue engineering promises to restore bone defects that are caused by
      severe trauma, congenital malformations, tumors, and nonunion fractures. How to
      effectively promote the proliferation and osteogenic differentiation of
      mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field.
      Many researchers are studying the ways of conferring a pro-osteodifferentiation
      or osteoinductive capability on implants or scaffold materials, where
      osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of
      coating material that may confer the pro-osteodifferentiation capability on
      implants and scaffold materials by surface modification. Here, we review recent
      studies on the effects of graphene on surface modifications of implants or
      scaffold materials. The ability of graphene to improve the mechanical and
      biological properties of implants or scaffold materials, such as nitinol and
      carbon nanotubes, and its ability to promote the adhesion, proliferation, and
      osteogenic differentiation of MSCs or osteoblasts have been demonstrated in
      several studies. Most previous studies were performed in vitro, but further
      studies will explore the mechanisms of graphene's effects on bone regeneration,
      its in vivo biocompatibility, its ability to promote osteodifferentiation, and
      its potential applications in bone tissue engineering. 

PMID- 24447042
TI  - Formation of microvascular networks: role of stromal interactions directing
      angiogenic growth.
AB  - In the adult, angiogenesis leads to an expanded microvascular network as new
      vessel segments are added to an existing microcirculation. Necessarily, growing
      neovessels must navigate through tissue stroma as they locate and grow toward
      other vessel elements. We have a growing body of evidence demonstrating that
      angiogenic neovessels reciprocally interact with the interstitial matrix of the
      stroma resulting in directed neovascular growth during angiogenesis. Given the
      compliance and the viscoelastic properties of collagen, neovessel guidance by the
      stroma is likely due to compressive strain transverse to the direction of primary
      tensile forces present during active tissue deformation. Similar stromal strains
      control the final network topology of the new microcirculation, including the
      distribution of arterioles, capillaries, and venules. In this case, stromal
      derived stimuli must be present during the post-angiogenesis remodeling and
      maturation phases of neovascularization to have this effect. Interestingly, the
      preexisting organization of vessels prior to the start of angiogenesis has no
      lasting influence on the final, new network architecture. Combined, the evidence
      describes interplay between angiogenic neovessels and stroma that is important in
      directed neovessel growth and invasion. This dynamic is also likely a mechanism
      by which global tissue forces influence vascular form and function.

PMID- 24447044
TI  - Serum microRNA levels in patients with Crohn's disease during induction therapy
      by infliximab.
AB  - BACKGROUND AND AIM: microRNAs (miRNAs) have been suggested to be candidates for
      biomarkers in various diseases including Crohn's disease (CD). To identify
      possible biomarkers predictive of the therapeutic effect of infliximab in CD, we
      investigated serum miRNA levels during the induction therapy by the medication.
      METHODS: Nineteen CD patients who were applied to the induction therapy by
      infliximab were enrolled. Serum samples for miRNA analyses were obtained at weeks
      0 and 6, and the therapeutic efficacy by infliximab was assessed according to the
      Crohn's disease activity index value at week 14. Exploratory miRNA profiling by
      low-density array was initially performed in three patients. The levels of
      candidate miRNA were subsequently determined by real-time polymerase chain
      reaction (PCR) assays in the remaining 16 patients. The miRNA levels during the
      induction therapy were compared between the two groups classified by the clinical
      response to infliximab at week 14. RESULTS: Low-density array analysis identified
      14 miRNAs that showed twofold or more altered expression during the induction
      therapy by infliximab. Subsequent analysis by real-time PCR demonstrated
      significantly increased levels of five miRNAs (let-7d, let-7e, miR-28-5p, miR
      221, and miR-224) at week 6 when compared with those at week 0 (P < 0.05 each).
      In addition, miRNA levels of let-7d and let-7e were significantly increased in
      the group of patients who achieved clinical remission by infliximab (P = 0.001
      and P = 0.002, respectively). CONCLUSION: let-7d and let-7e might be possible
      therapeutic biomarkers in patients with CD, who are treated by infliximab.

PMID- 24447043
TI  - Effect of brown rice, white rice, and brown rice with legumes on blood glucose
      and insulin responses in overweight Asian Indians: a randomized controlled trial.
AB  - BACKGROUND: Improving the carbohydrate quality of the diet by replacing the
      common cereal staple white rice (WR) with brown rice (BR) could have beneficial
      effects on reducing the risk for diabetes and related complications. Hence we
      aimed to compare the effects of BR, WR, and BR with legumes (BRL) diets on 24-h
      glycemic and insulinemic responses among overweight Asian Indians. SUBJECTS AND
      METHODS: Fifteen overweight (body mass index, >=23 kg/m(2)) Asian Indians without
      diabetes who were 25-45 years old participated in a randomized crossover study.
      Test meals (nonisocaloric, ad libitum) were identical except for the type of rice
      and the addition of legumes (50 g/day) and were provided for 5 consecutive days.
      Glucose profiles were assessed using the Medtronic MiniMed (Northridge, CA)
      iProTM2 continuous glucose monitoring device. The mean positive change from
      baseline glucose concentration was calculated as the daily incremental area under
      the curve (IAUC) on each test day for 5 days and averaged. Fasting serum insulin
      was measured prior to and at the end of each test diet. RESULTS: The percentage
      difference in 5-day average IAUC was 19.8% lower in the BR group than in the WR
      group (P=0.004). BRL further decreased the glycemic response (22.9% lower
      compared with WR (P=0.02). The 5-day percentage change in fasting insulin was 57%
      lower (P=0.0001) for the BR group and 54% lower for the BRL group compared with
      the 5-day percentage change observed in the WR group. The glycemic and
      insulinemic responses to the BR and BRL diets were not significantly different.
      CONCLUSIONS: Consumption of BR in place of WR can help reduce 24-h glucose and
      fasting insulin responses among overweight Asian Indians.

PMID- 24447045
TI  - Evolution of granuloma annulare to mid-dermal elastolysis: report of a case and
      review of the literature.
AB  - A 55-year-old healthy Caucasian female, on no medication, was seen by a
      dermatologist because of a patchy, slightly indurated and violaceous eruption
      involving her neck and trunk. The clinical impression was of granuloma annulare
      (GA). Over a period of several months the violaceous lesions became atrophic with
      loss of colour and eventual wrinkling of lesional skin. Sequential skin biopsies
      were obtained, which revealed a spectrum of changes. Those from early violaceous
      lesional zones displayed perivascular lymphocytic infiltrates and interstitial
      granulomatous inflammation, characteristic of interstitial GA. Samples from
      atrophic lesional areas appeared normal on routine sections but an Orcein-Giemsa
      (OG) stain, prompted by the clinical history of atrophy, revealed absence of
      elastic fibers in the mid-reticular dermis. The combined clinicopathologic
      findings pointed to development of mid-dermal elastolysis (MDE) at involutional
      sites of GA. Owing to consideration of a cutaneous T-cell lymphoma in the
      differential diagnosis, genotyping in search of T-cell monoclonality was
      performed and yielded a negative result. Our case supports the existing but scant
      evidence in the literature that the rare, enigmatic condition termed MDE is an
      end-result of inflammatory destruction of dermal elastic fibers. GA is one form
      of dermatitis capable of culminating in this entity, but others have also been
      implicated. 

PMID- 24447046
TI  - Environmental pollutants: downgrading the fish food stock affects chronic disease
      risk.

PMID- 24447047
TI  - Chemical composition, properties, and antimicrobial activity of the water-soluble
      pigments from Castanea mollissima shells.
AB  - Agricultural residues Castanea mollissima shells represent a promising resource
      for natural pigments for the food industry. This study provides a comprehensive
      and systematic evaluation of water-soluble pigments (CSP) from C. mollissima
      shells, which were obtained by 50% ethanol with microwave-assisted extraction.
      Spectroscopic techniques (UV, FT-IR, (13)C NMR), elemental analysis, and
      chromatographic techniques (HPAEC, GPC) revealed that the main components in the
      CSP were flavonoids procyanidin B3 (condensed tannin), quercetin-3-O-glycoside,
      and steroidal sapogenins. As a consequence, CSP was water-soluble and presented
      significant DPPH scavenge capacity (EC50 value was 0.057 mg/mL). Specially, CSP
      gave excellent antibacterial activity, and even better than 5% aqueous phenol in
      some case. Moreover, CSP was practically nontoxic and exhibited good stability
      with temperature, natural light, and metal ions. These outstanding properties
      will enlarge the application of CSP for natural food additives production. 

PMID- 24447048
TI  - Inherited blistering skin diseases: underlying molecular mechanisms and emerging
      therapies.
AB  - A key function of human skin is the formation of a structural barrier against the
      external environment. In part, this is achieved through the formation of a
      cornified cell envelope derived from a stratified squamous epithelium attached to
      an epithelial basement membrane. Resilient in health, the structural integrity of
      skin can become impaired or break down in a collection of inherited skin
      diseases, referred to as the blistering genodermatoses. These disorders arise
      from inherited gene mutations in a variety of structural and signalling proteins
      and manifest clinically as blisters or erosions following minor skin trauma. In
      some patients, blistering can be severe resulting in significant morbidity.
      Furthermore, a number of these conditions are associated with debilitating extra
      cutaneous manifestations including gastro-intestinal, cardiac, and ocular
      complications. In recent years, an improved understanding of the molecular basis
      of the blistering genodermatoses has led to better disease classification and
      genetic counselling. For patients, this has also advanced translational research
      with the advent of new clinical trials of gene, protein, cell, drug, and small
      molecule therapies. Although curing inherited blistering skin diseases still
      remains elusive, significant improvements in patients' quality of life are
      already being achieved.

PMID- 24447049
TI  - Selective sensitization to Penicillin V with tolerance to other betalactams.
AB  - BACKGROUND: Penicillin G and V have the same betalactam ring. Penicillin V
      (phenoxymethylpenicillin) results from the substitution of the phenyl acetic acid
      of benzylpenicillin by the phenoxy methyl side chain. METHODS: Our patient was a
      34-year-old man who experienced generalized urticaria after ingestion of
      Penicillin V. We performed skin prick tests and intradermal tests with a battery
      of betalactams including Penicillin V. We also determined specific IgE against
      penicillin V, penicillin G, amoxicillin, and ampicillin and performed a single
      blind oral challenge with Penicillin V, amoxicillin, cefuroxime, and ceftazidime.
      RESULTS: The results of skin prick and intradermal tests with the betalactams
      included were negative. Specific IgE with betalactams was < 0.10 IU/L. The result
      of a single-blind oral challenge with Penicillin V was positive: 40 minutes after
      receiving 125 mg of Penicillin V, the patient presented generalized pruritus with
      hives on his back and chest. He tolerated oral administration of amoxicillin,
      cefuroxime, and ceftazidime. CONCLUSION: We report an exceptional case of
      sensitization to Penicillin V with negative results in the allergy workup.
      Diagnosis was based on a positive single-blind oral challenge result. The patient
      tolerated other betalactams. We provide a brief summary of the most relevant
      recent patents.

PMID- 24447050
TI  - Modifying anti-inflammatory effect of Diclofenac with Murraya koenigii.
AB  - Murraya koenigii (Curry leaves) has been widely used in Asian countries for the
      treatment of some ailments such as diabetes and hypertension. In the present
      study, leaves of Murraya koenigii were extracted with ethanol and evaluated for
      anti-inflammatory activity in rats using carrageenan induced paw edema method.
      Ethanolic extract showed a potent anti-inflammatory activity at third hour after
      carrageenan administration when compared with the standard drug, Diclofenac. The
      percent inhibition of paw volume was found to be 84.75% for 50 mg/kg of extract
      whereas it was found to be 80.86% for 50 mg/kg extract in combination with
      Diclofenac 10 mg/kg. Thus, the present study suggests that the combination
      therapy potentiates the anti-inflammatory effect of diclofenac and may help in
      reducing the dose of the synthetic drug. Some relevant patents are also outlined
      in this article. 

PMID- 24447051
TI  - Double jeopardy in the echocardiography laboratory: coexistence of two distinct
      cardiomyopathies?
AB  - BACKGROUND: In our Hypertrophic Cardiomyopathy (HCM) Center, we identified 6
      patients each with what appeared to be the occurrence of 2 rare diseases that
      prompted investigation for a common derivative. METHODS: We reviewed our
      database, searching for all patients with a diagnosis of HCM, amyloid heart
      disease and left ventricular noncompaction (LVNC). RESULTS: Using transthoracic
      echocardiography and magnetic resonance imaging, we identified 6 patients with
      apical hypertrabeculations and myocardium suggestive of LVNC; 4 of the patients
      had HCM and 2 of the patients had cardiac amyloidosis. CONCLUSIONS: The
      significance of these possible concomitant cardiomyopathies is not presently well
      understood. We did not identify a common derivative when looking for a genetic
      link, but it is most likely hidden in the genetic substrate, yet to be
      identified.

PMID- 24447052
TI  - Reply to the letter to the editor by George et Al.

PMID- 24447053
TI  - Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from
      subgenual anterior cingulate functional connectivity.
AB  - OBJECTIVES: Intensified repetitive transcranial magnetic stimulation (rTMS)
      applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast
      clinical responses in treatment resistant depression (TRD). In these kinds of
      patients, subgenual anterior cingulate cortex (sgACC) functional connectivity
      (FC) seems to be consistently disturbed. So far, no de novo data on the
      relationship between sgACC FC changes and clinical efficacy of accelerated rTMS
      were available. METHODS: Twenty unipolar TRD patients, all at least stage III
      treatment resistant, were recruited in a randomized sham-controlled crossover
      high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans
      were collected at baseline and at the end of treatment. RESULTS: HF-rTMS
      responders showed significantly stronger resting-state functional connectivity
      (rsFC) anti-correlation between the sgACC and parts of the left superior medial
      prefrontal cortex. After successful treatment an inverted relative strength of
      the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC).
      No effects on sgACC rsFC were observed in non-responders. CONCLUSIONS: Strong
      rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex
      could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment
      designs have the potential to acutely adjust deregulated sgACC neuronal networks
      in TRD patients.

PMID- 24447054
TI  - Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve
      cognition in psychiatric disorders?
AB  - OBJECTIVES: Since the discovery of psychopharmacological treatments in the early
      1950s, followed by the development of second-generation antidepressants and
      antipsychotics, biological psychiatry has not achieved much progress. Recent
      technological advances in the field of non-invasive brain stimulation open new
      perspectives in the treatment of psychiatric disorders. Amongst them,
      transcranial direct current stimulation (tDCS) modulates cortical excitability
      and induces long-lasting effects. Here, we aimed at evaluating whether tDCS has
      potential to be developed as an innovative treatment in psychiatry. METHODS: We
      conducted a systematic review of the current state of development and application
      of tDCS in psychiatric disorders, exploring clinical and cognitive effects,
      especially in major depressive disorder (MDD), schizophrenia and substance use
      disorder. RESULTS: Systematic literature search yielded 40 publications: 22 in
      MDD, nine in schizophrenia, seven in substance use disorder, one in obsessive
      compulsive disorder and one in mania. Our findings indicated beneficial clinical
      effects of tDCS for MDD and a promising literature in schizophrenia and substance
      use disorder. CONCLUSIONS: Despite methodological differences, the data published
      to date are promising and supports the use of tDCS as a treatment for psychiatric
      disorders. However, its place regarding other treatments still has to be
      determined before becoming a routine clinical treatment.

PMID- 24447055
TI  - Structure and function of the genomically encoded fosfomycin resistance enzyme,
      FosB, from Staphylococcus aureus.
AB  - The Gram-positive pathogen Staphylococcus aureus is a leading cause of global
      morbidity and mortality. Like many multi-drug-resistant organisms, S. aureus
      contains antibiotic-modifying enzymes that facilitate resistance to a multitude
      of antimicrobial compounds. FosB is a Mn(2+)-dependent fosfomycin-inactivating
      enzyme found in S. aureus that catalyzes nucleophilic addition of either l
      cysteine (l-Cys) or bacillithiol (BSH) to the antibiotic, resulting in a modified
      compound with no bactericidal properties. The three-dimensional X-ray crystal
      structure of FosB from S. aureus (FosB(Sa)) has been determined to a resolution
      of 1.15 A. Cocrystallization of FosB(Sa) with either l-Cys or BSH results in a
      disulfide bond between the exogenous thiol and the active site Cys9 of the
      enzyme. An analysis of the structures suggests that a highly conserved loop
      region of the FosB enzymes must change conformation to bind fosfomycin. While two
      crystals of FosB(Sa) contain Zn(2+) in the active site, kinetic analyses of
      FosB(Sa) indicated that the enzyme is inhibited by Zn(2+) for l-Cys transferase
      activity and only marginally active for BSH transferase activity. Fosfomycin
      treated disk diffusion assays involving S. aureus Newman and the USA300 JE2
      methicillin-resistant S. aureus demonstrate a marked increase in the sensitivity
      of the organism to the antibiotic in either the BSH or FosB null strains,
      indicating that both are required for survival of the organism in the presence of
      the antibiotic. This work identifies FosB as a primary fosfomycin-modifying
      pathway of S. aureus and establishes the enzyme as a potential therapeutic target
      for increased efficacy of fosfomycin against the pathogen. 

PMID- 24447056
TI  - Translating the link between social identity and health behavior into effective
      health communication strategies: An experimental application using antismoking
      advertisements.
AB  - Social identity is a construct that has been linked to health behavior. Yet,
      limited research has attempted to translate this relationship into health
      communication strategies. The current study addresses this gap by examining the
      efficacy of social identity targeting (constructing ads so that they target a
      specific group with which an individual identifies) to increase anti-cigarette
      smoking beliefs among adolescents. Two hundred and fifty one adolescents aged 12
      15, randomly selected from a nationally representative sample, completed an
      online survey. Participants indicated which of 11 peer groups (determined in pre
      testing) they most identified with. Each participant was then randomly assigned
      to view an ad that either did or did not target that group. One week later
      participants reported level of agreement with two key antismoking beliefs
      presented in the ad. Multiple regression analyses indicated that if an individual
      identified with the group targeted by the ad, antismoking beliefs were more
      strongly endorsed. Based on these findings, we conclude that social identity
      targeting has the potential to increase the effectiveness of antismoking messages
      and should be considered when designing antismoking campaigns.

PMID- 24447057
TI  - Staying 'in the zone' but not passing the 'point of no return': embodiment,
      gender and drinking in mid-life.
AB  - Public health approaches have frequently conceptualised alcohol consumption as an
      individual behaviour resulting from rational choice. We argue that drinking
      alcohol needs to be understood as an embodied social practice embedded in
      gendered social relationships and environments. We draw on data from 14 focus
      groups with pre-existing groups of friends and work colleagues in which men and
      women in mid-life discussed their drinking behaviour. Analysis demonstrated that
      drinking alcohol marked a transitory time and space that altered both women's and
      men's subjective embodied experience of everyday gendered roles and
      responsibilities. The participants positioned themselves as experienced drinkers
      who, through accumulated knowledge of their own physical bodies, could achieve
      enjoyable bodily sensations by reaching a desired level of intoxication (being in
      the zone). These mid-life adults, particularly women, discussed knowing when they
      were approaching their limit and needed to stop drinking. Experiential and
      gendered embodied knowledge was more important in regulating consumption than
      health promotion advice. These findings foreground the relational and gendered
      nature of drinking and reinforce the need to critically interrogate the concept
      of alcohol consumption as a simple health behaviour. Broader theorising around
      notions of gendered embodiment may be helpful for more sophisticated
      conceptualisations of health practices. 

PMID- 24447060
TI  - Advancing complex explanatory conceptualizations of daily negative and positive
      affect: trigger and maintenance coping action patterns.
AB  - The present study addressed a fundamental gap between research and clinical work
      by advancing complex explanatory conceptualizations of coping action patterns
      that trigger and maintain daily negative affect and (low) positive affect. One
      hundred ninety-six community adults completed measures of perfectionism, and then
      6 months later completed questionnaires at the end of the day for 14 consecutive
      days to provide simultaneous assessments of appraisals, coping, and affect across
      different stressful situations in everyday life. Multilevel structural equation
      modeling (MSEM) supported complex explanatory conceptualizations that
      demonstrated (a) disengagement trigger patterns consisting of several distinct
      appraisals (e.g., event stress) and coping strategies (e.g., avoidant coping)
      that commonly operate together across many different stressors when the typical
      individual experiences daily increases in negative affect and drops in positive
      affect; and (b) disengagement maintenance patterns composed of different
      appraisal and coping maintenance factors that, in combination, can explain why
      individuals with higher levels of self-critical perfectionism have persistent
      daily negative affect and low positive mood 6 months later. In parallel,
      engagement patterns (triggers and maintenance) composed of distinct appraisals
      (e.g., perceived social support) and coping strategies (e.g., problem-focused
      coping) were linked to compensatory experiences of daily positive affect. These
      findings demonstrate the promise of using daily diary methodologies and MSEM to
      promote a shared understanding between therapists and clients of trigger and
      maintenance coping action patterns that explain what precipitates and perpetuates
      clients' difficulties, which, in turn, can help achieve the 2 overarching therapy
      goals of reducing clients' distress and bolstering resilience.

PMID- 24447061
TI  - Developing a comprehensive scale to assess college multicultural programming.
AB  - A barrier to assessing effectiveness of multicultural programming is lack of a
      relatively brief instrument to measure the wide range of intended outcomes. A
      frequent goal of programming is to increase cultural empathy, but this is rarely
      the only intended outcome. We conducted focus groups of campus administrators,
      student affairs staff, and undergraduate instructors who identified a full range
      of racial/ethnic multicultural competencies that undergraduates should possess.
      An 84-item pool generated from these focus groups was combined with the 31-item
      Scale of Ethnocultural Empathy (SEE; Wang et al., 2003). These 115 items,
      together with instruments used to gauge concurrent validity, were administered to
      White undergraduate students in introductory psychology courses at the midpoint
      (n = 602) and end (n = 676) of fall semester. Exploratory factor analysis
      suggested 6 subscales for the Everyday Multicultural Competencies/Revised SEE
      (EMC/RSEE): (a) Cultural Openness and Desire to Learn; (b) Resentment and
      Cultural Dominance; (c) Anxiety and Lack of Multicultural Self-Efficacy; (d)
      Empathic Perspective-Taking; (e) Awareness of Contemporary Racism and Privilege;
      and (f) Empathic Feeling and Acting as an Ally. Item response theory principles
      guided final selection of subscale items. Analyses suggested good factor
      stability, reliability, and discriminant validity of the 48-item EMC/RSEE in
      these undergraduate samples. EMC/RSEE subscales were not strongly correlated with
      a measure of impression management and were significantly associated with
      measures of Openness to Diversity Challenge, and Universal-Diverse Orientation.

PMID- 24447063
TI  - Evaluation of Kilifi epilepsy education programme: a randomized controlled trial.
AB  - OBJECTIVES: The epilepsy treatment gap is largest in resource-poor countries. We
      evaluated the efficacy of a 1-day health education program in a rural area of
      Kenya. The primary outcome was adherence to antiepileptic drugs (AEDs) as
      measured by drug levels in the blood, and the secondary outcomes were seizure
      frequency and Kilifi Epilepsy Beliefs and Attitudes Scores (KEBAS). METHODS:
      Seven hundred thirty-eight people with epilepsy (PWE) and their designated
      supporter were randomized to either the intervention (education) or
      nonintervention group. Data were collected at baseline and 1 year after the
      education intervention was administered to the intervention group. There were 581
      PWE assessed at both time points. At the end of the study, 105 PWE from the
      intervention group and 86 from the nonintervention group gave blood samples,
      which were assayed for the most commonly used AEDs (phenobarbital, phenytoin, and
      carbamazepine). The proportions of PWE with detectable AED levels were determined
      using a standard blood assay method. The laboratory technicians conducting the
      assays were blinded to the randomization. Secondary outcomes were evaluated using
      questionnaires administered by trained field staff. Modified Poisson regression
      was used to investigate the factors associated with improved adherence
      (transition from nonoptimal AED level in blood at baseline to optimal levels at
      follow-up), reduced seizures, and improved KEBAS, which was done as a post hoc
      analysis. This trial is registered in ISRCTN register under ISRCTN35680481.
      RESULTS: There was no significant difference in adherence to AEDs based on
      detectable drug levels (odds ratio [OR] 1.46, 95% confidence interval [95% CI]
      0.74-2.90, p = 0.28) or by self-reports (OR 1.00, 95% CI 0.71-1.40, p = 1.00)
      between the intervention and nonintervention group. The intervention group had
      significantly fewer beliefs about traditional causes of epilepsy, cultural
      treatment, and negative stereotypes than the nonintervention group. There was no
      difference in seizure frequency. A comparison of the baseline and follow-up data
      showed a significant increase in adherence-intervention group (36-81% [p <
      0.001]) and nonintervention group (38-74% [p < 0.001])-using detectable blood
      levels. The number of patients with less frequent seizures (<=3 seizures in the
      last 3 months) increased in the intervention group (62-80% [p = 0.002]) and in
      the nonintervention group (67-75% [p = 0.04]). Improved therapeutic adherence
      (observed in both groups combined) was positively associated with positive change
      in beliefs about risks of epilepsy (relative risk [RR] 2.00, 95% CI 1.03-3.95)
      and having nontraditional religious beliefs (RR 2.01, 95% CI 1.01-3.99). Reduced
      seizure frequency was associated with improved adherence (RR 1.72, 95% CI 1.19
      2.47). Positive changes in KEBAS were associated with having tertiary education
      as compared to none (RR 1.09, 95% CI 1.05-1.14). SIGNIFICANCE: Health education
      improves knowledge about epilepsy, but once only contact does not improve
      adherence. However, sustained education may improve adherence in future studies.

PMID- 24447065
TI  - Dual matrix-based immobilized trypsin for complementary proteolytic digestion and
      fast proteomics analysis with higher protein sequence coverage.
AB  - In an age of whole-genome analysis, the mass spectrometry-based bottom-up
      strategy is now considered to be the most powerful method for in-depth proteomics
      analysis. As part of this strategy, highly efficient and complete proteolytic
      digestion of proteins into peptides is crucial for successful proteome profiling
      with deep coverage. To achieve this goal, prolonged digestion time and the use of
      multiple proteases have been adopted. The long digestion time required and
      tedious sample treatment steps severely limit the sample processing throughput.
      Though utilization of immobilized protease greatly reduces the digestion time,
      highly efficient proteolysis of extremely complex proteomic samples remains a
      challenging task. Here, we propose a dual matrix-based complementary digestion
      method using two types of immobilized trypsin with opposite matrix hydrophobicity
      prepared by attaching trypsin on hydrophobic or hydrophilic polymer-brush
      modified nanoparticles. The polymer brushes on the nanoparticles serve as three
      dimensional supports for a large amount of trypsin immobilization and lead to
      ultrafast and highly efficient protein digestion. More importantly, the two types
      of immobilized trypsin show high complementarity in protein digestion with only
      ~60% overlap in peptide identification for yeast and membrane protein of mouse
      liver. Complementary digestion by applying these two types of immobilized trypsin
      together leads to obviously enhanced protein and peptide identification.
      Furthermore, the dual matrix-based complementary digestion shows particular
      advantage in the digestion of membrane proteins, as twice the number of
      identified peptides is obtained compared with solution digestion using free
      proteases, demonstrating its potential as a promising alternative to promote
      proteomics analysis with higher protein sequence coverage. 

PMID- 24447064
TI  - Remodeling natural products: chemistry and serine hydrolase activity of a
      rocaglate-derived beta-lactone.
AB  - Flavaglines are a class of natural products with potent insecticidal and
      anticancer activities. beta-Lactones are a privileged structural motif found in
      both therapeutic agents and chemical probes. Herein, we report the synthesis,
      unexpected light-driven di-epimerization, and activity-based protein profiling of
      a novel rocaglate-derived beta-lactone. In addition to in vitro inhibition of the
      serine hydrolases ABHD10 and ACOT1/2, the most potent beta-lactone enantiomer was
      also found to inhibit these enzymes, as well as the serine peptidases CTSA and
      SCPEP1, in PC3 cells. 

PMID- 24447068
TI  - Metabolic syndrome in Turner syndrome and relation between body composition and
      clinical, genetic, and ultrasonographic characteristics.
AB  - BACKGROUND: An increased relative risk of diabetes, ischemic heart disease,
      atherosclerosis, and hypertension have been reported in Turner syndrome (TS)
      patients. No data are currently available on the prevalence of metabolic syndrome
      in TS subjects. We evaluated the frequency of metabolic syndrome in obese and
      nonobese patients with TS. PATIENTS AND METHODS: We evaluated 85 TS patients
      (27.05 +/- 11.17 years). Obesity was defined as standard deviation score body
      mass index (SDS-BMI) >= 2 or BMI >= 30 kg/m(2) in adult patients. We classified
      metabolic syndrome according to the International Diabetes Federation (IDF).
      Hepatic ultrasound was performed in all girls. RESULTS: The prevalence of
      metabolic syndrome was 4.7% (12.5% obese and 4.3% nonobese, P=0.16) and
      associated with visceral adiposity (P=0.008). Abnormalities in glucose metabolism
      and hypertension were not associated with genetic or therapeutic factors. The
      karyotype 45,X was associated with atherogenic profile. Pathological waist
      circumference was more frequent in girls treated with estro-progestin (P=0.03).
      Evidence of fatty liver was associated with metabolic syndrome (P=0.03) and
      insulin resistance (P=0.05). Elevated liver enzymes were found in 15 subjects and
      were not related to treatment or ultrasound abnormalities. CONCLUSIONS:
      Prevalence of each component of metabolic syndrome in TS patients is partially
      influenced by genetic makeup and treatment. Hepatosteatosis was associated with
      metabolic syndrome and insulin resistance, but not to elevated liver enzymes.

PMID- 24447069
TI  - A polymerase chain reaction-based method for isolating clones from a
      complimentary DNA library in sheep.
AB  - The sheep (Ovis aries) is favored by many musculoskeletal tissue engineering
      groups as a large animal model because of its docile temperament and ease of
      husbandry. The size and weight of sheep are comparable to humans, which allows
      for the use of implants and fixation devices used in human clinical practice. The
      construction of a complimentary DNA (cDNA) library can capture the expression of
      genes in both a tissue- and time-specific manner. cDNA libraries have been a
      consistent source of gene discovery ever since the technology became commonplace
      more than three decades ago. Here, we describe the construction of a cDNA library
      using cells derived from sheep bones based on the pBluescript cDNA kit. Thirty
      clones were picked at random and sequenced. This led to the identification of a
      novel gene, C12orf29, which our initial experiments indicate is involved in
      skeletal biology. We also describe a polymerase chain reaction-based cDNA clone
      isolation method that allows the isolation of genes of interest from a cDNA
      library pool. The techniques outlined here can be applied in-house by smaller
      tissue engineering groups to generate tools for biomolecular research for large
      preclinical animal studies and highlights the power of standard cDNA library
      protocols to uncover novel genes.

PMID- 24447071
TI  - Facile preparation of ultra-large pore mesoporous silica nanoparticles and their
      application to the encapsulation of large guest molecules.
AB  - Pore-enlarged mesoporous silica nanoparticles (MSNs) were prepared directly from
      as-prepared MSNs through a new, simple method using divalent Ca or Mg salts as
      both efficient silica etching reagents and as ion exchangers in methanolic
      solution under mild conditions. The resultant MSNs became almost template-free
      simultaneously during this etching process. The pore-enlarged MSNs, referred to
      as Ca-MSN or Mg-MSN, maintained their original hexagonal pore symmetry and
      particle sizes, but several ultra-large mesopores were generated inside and
      outside the MSNs together with regular mesopores having expanded pore dimension
      of around 4-5 nm. The average pore diameters for ultra-large pores were 47.5 nm
      for Ca-MSN and 52.4 nm for Mg-MSN. The generation of ultra-large pores can be
      regarded as the collapse of several mesopores into an ultra-large pore. Both Ca
      MSN and Mg-MSN were good sorbents for positively charged porphyrin molecules.
      Additionally, these ultra-large pore MSNs exhibited better adsorption ability
      than calcined MSN for large proteins and antibodies, such as bovine serum albumin
      (BSA) and immunoglobulin G (IgG). 

PMID- 24447070
TI  - Effects of a novel orally administered calpain inhibitor SNJ-1945 on
      immunomodulation and neurodegeneration in a murine model of multiple sclerosis.
AB  - Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin
      specific T cells into the CNS. Hallmarks of T helper (Th) cells during active
      disease are pro-inflammatory Th1/Th17 cells that predominate over
      immunoregulatory Th2/Treg cells. Neurodegeneration, a major factor in progressive
      MS, is often overlooked when considering drug prescription. Here, we show that
      oral dosing with SNJ-1945, a novel water-soluble calpain inhibitor, reduces
      experimental autoimmune encephalomyelitis clinical scores in vivo and has a two
      pronged effect via anti-inflammation and protection against neurodegeneration. We
      also show that SNJ-1945 treatment down-regulates Th1/Th17 inflammatory responses,
      and promotes regulatory T cells (Tregs) and myeloid-derived suppressor cells in
      vivo, which are known to have the capacity to suppress helper as well as
      cytotoxic T cell functions. Through analysis of spinal cord samples, we show a
      reduction in calpain expression, decreased infiltration of inflammatory cells,
      and signs of inhibition of neurodegeneration. We also show a marked reduction in
      neuronal cell death in spinal cord (SC) sections. These results suggest that
      calpain inhibition attenuates experimental autoimmune encephalomyelitis pathology
      by reducing both inflammation and neurodegeneration, and could be used in
      clinical settings to augment the efficacy of standard immunomodulatory agents
      used to treat MS. Multiple sclerosis (MS) pathology is marked by inflammation and
      infiltration of myelin-specific T cells into the central nervous system.
      Inflammation leads to neurodegeneration in progressive MS which also leads to
      epitope spreading, feedback looping to more inflammation. Calpain can play a role
      in both arms of the disease. Here, oral dosing with SNJ-1945, a novel water
      soluble calpain inhibitor, reduces experimental autoimmune encephalomyelitis
      clinical scores in vivo and has a two-pronged effect via anti-inflammation and
      protection against neurodegeneration. 

PMID- 24447072
TI  - Exercise training-induced adaptations in mediators of sustained endothelium
      dependent coronary artery relaxation in a porcine model of ischemic heart
      disease.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that exercise
      training enhances sustained relaxation to persistent endothelium-dependent
      vasodilator exposure via increased nitric oxide contribution in small coronary
      arteries of control and ischemic hearts. METHODS: Yucatan swine were designated
      to a control group or a group in which an ameroid constrictor was placed around
      the proximal LCX. Subsequently, pigs from both groups were assigned to exercise
      (five days/week; 16 weeks) or SED regimens. Coronary arteries (~100-350 MUm) were
      isolated from control pigs and from both nonoccluded and collateral-dependent
      regions of chronically-occluded hearts. RESULTS: In arteries from control pigs,
      training significantly enhanced relaxation responses to increasing concentrations
      of bradykinin (10(-10) -10(-7) M) and sustained relaxation to a single bradykinin
      concentration (30 nM), which were abolished by NOS inhibition. Training also
      significantly prolonged bradykinin-mediated relaxation in collateral-dependent
      arteries of occluded pigs, which was associated with more persistent increases in
      endothelial cellular Ca(2+) levels, and reversed with NOS inhibition. Protein
      levels for eNOS and p-eNOS-(Ser1179), but not caveolin-1, Hsp90, or Akt, were
      significantly increased with occlusion, independent of training state.
      CONCLUSIONS: Exercise training enhances sustained relaxation to endothelium
      dependent agonist stimulation in small arteries of control and ischemic hearts by
      enhanced nitric oxide contribution and endothelial Ca(2+) responses.

PMID- 24447074
TI  - The PILGRIM study: in silico modeling of a predictive low glucose management
      system and feasibility in youth with type 1 diabetes during exercise.
AB  - BACKGROUND: Predictive low glucose management (PLGM) may help prevent
      hypoglycemia by stopping insulin pump delivery based on predicted sensor glucose
      values. MATERIALS AND METHODS: Hypoglycemic challenges were simulated using the
      Food and Drug Administration-accepted glucose simulator with 100 virtual
      patients. PLGM was then tested with a system composed of a Paradigm((r)) insulin
      pump (Medtronic, Northridge, CA), an EnliteTM glucose sensor (Medtronic), and a
      BlackBerry((r)) (Waterloo, ON, Canada)-based controller. Subjects (n=22) on
      continuous subcutaneous insulin infusion (five females, 17 males; median [range]
      age, 15 [range, 14-20] years; median [range] diabetes duration, 7 [2-14] years;
      median [range] glycated hemoglobin, 8.0% [6.7-10.4%]) exercised until the PLGM
      system suspended insulin delivery or until the reference blood glucose value
      (HemoCue((r)); HemoCue GmbH, Grobetaostheim, Germany) reached the predictive
      suspension threshold setting. RESULTS: PLGM reduced hypoglycemia (<70 mg/dL) in
      silico by 26.7% compared with no insulin suspension, as opposed to a 5.3%
      reduction in hypoglycemia with use of low glucose suspend (LGS). The median
      duration of hypoglycemia (time spent <70 mg/dL) with PLGM was significantly less
      than with LGS (58 min vs. 101 min, respectively; P<0.001). In the clinical trial
      the hypoglycemic threshold during exercise was reached in 73% of the patients,
      and hypoglycemia was prevented in 80% of the successful experiments. The mean (+/
      SD) sensor glucose at predictive suspension was 92+/-7 mg/dL, resulting in a
      postsuspension nadir (by HemoCue) of 77+/-22 mg/dL. The suspension lasted for
      90+/-35 (range, 30-120) min, resulting in a sensor glucose level at insulin
      resumption of 97+/-19 mg/dL. CONCLUSIONS: In silico modeling and early
      feasibility data demonstrate that PLGM may further reduce the severity of
      hypoglycemia beyond that already established for algorithms that use a threshold
      based suspension.

PMID- 24447075
TI  - Nodular secondary syphilis with associated granulomatous inflammation: case
      report and literature review.
AB  - A 62-year-old male presented with a 10-day history of a diffuse, erythematous
      papular rash sparing the palms and soles. Histopathologic examination of a skin
      lesion showed loose non-caseating granulomas in a lymphoplasmacytic background.
      Scattered spirochetes were identified by Treponema pallidum immunohistochemistry,
      in keeping with a diagnosis of secondary syphilis. Granulomatous inflammation in
      secondary syphilis is uncommon. A review of the literature reveals that the
      majority of prior reported cases of granulomatous secondary syphilis share
      similar characteristics to this case; namely, a papular or nodular clinical
      presentation, sparing of the palms and soles, and collections of epithelioid
      histiocytes with associated lymphocytes and variable numbers of plasma cells. 

PMID- 24447076
TI  - Identification and analysis of novel R308K mutation in glucokinase of type 2
      diabetic patient and its kinetic correlation.
AB  - Glucokinase (GK) plays a critical role in glucose homeostasis and the mutations
      in GK gene result in pathogenic complications known as Maturity Onset Diabetes of
      the Young 2, an autosomal dominant form of diabetic condition. In the present
      study, GK was purified from human liver tissue and the pure enzyme showed single
      band in SDS-PAGE with a molecular weight of 50 kDa. The kinetics of pure GK
      showed enzyme activity of 0.423+/-0.02 uM glucose-6-phosphate (G6P)/mL/Min and Km
      value of 6.66+/-0.02 uM. These values were compared in the liver biopsy of a
      clinically proven type 2 diabetic patient, where GK kinetics showed decreased
      enzyme activity of 0.16+/-0.025 uM G6P/mL/Min and increased Km of 23+/-0.9 uM,
      indicating the hyperglycemic condition in the patient. The genetic analysis of
      10th exon of GK gene from this patient showed a R308K mutation. To substantiate
      these results, comparative molecular dynamics and docking studies were carried
      out where a higher docking score (-10.218 kcal/mol) was observed in the mutated
      GK than wild-type GK structure (-12.593 kcal/mol) indicating affinity variations
      for glucose. During the simulation process, glucose was expelled out from the
      mutant conformation but not from wild-type GK, making glucose unavailable for
      phosphorylation. Therefore, these results conclusively explain hyperglycemic
      condition in this patient.

PMID- 24447078
TI  - Exacerbation-prone asthma--intrinsic to severe disease or a unique phenotype?

PMID- 24447079
TI  - Too much of a good thing: beta-chain overexpression blocks FcepsilonRI signalling
      by capturing Lyn in the cytosol.

PMID- 24447080
TI  - Carrying peptides towards the ideal allergen-specific immunotherapy.

PMID- 24447081
TI  - Mapping of TLR5 and TLR7 in central and distal human airways and identification
      of reduced TLR expression in severe asthma.
AB  - BACKGROUND: The toll-like receptors, TLR5 and TLR7, have recently been proposed
      in asthma immunopathogenesis. While supporting data come from animal or in vitro
      studies, little is known about TLR5 and TLR7 expression in human asthmatic
      airways. METHODS: Advanced immunohistochemical mapping of TLR5 and TLR7 was
      performed on bronchial and transbronchial biopsies from healthy individuals and
      patients with moderate and severe asthma. RESULTS: TLR5 was identified in
      multiple structural cells; bronchial epithelium, alveolar type II pneumocytes,
      plasma cells, macrophages and neutrophils. Contrary to bronchial TLR5, which had
      a basolateral expression, alveolar TLR5 had polarized apical localization.
      Patients with severe asthma had decreased total and epithelial TLR5 expression
      compared to controls and moderate asthmatics (P < 0.001). TLR7 expression was
      found in several structural cells and asthma-related immune cells. Whereas TLR7
      expression was decreased in severe asthmatics (P < 0.001), nerve-associated TLR7
      increased (P = 0.035). Within the asthma groups, both TLR5 and TLR7 expression
      correlated with multiple lung function parameters. CONCLUSIONS: Our results
      reveal broad expression patterns of TLR5 and TLR7 in the lung and that the
      expression is decreased in severe asthma. Hence, severe asthmatics may suffer
      from insufficient TLR signalling during viral or bacterial infections leading to
      poor and impaired defence mechanisms.

PMID- 24447082
TI  - Differential expression of 11beta-hydroxysteroid dehydrogenase type 1 and 2 in
      mild and moderate/severe persistent allergic nasal mucosa and regulation of their
      expression by Th2 cytokines: asthma and rhinitis.
AB  - BACKGROUND: Glucocorticoids are used to treat allergic rhinitis, but the
      mechanisms by which they induce disease remission are unclear. 11beta
      hydroxysteroid dehydrogenase (11beta-HSD) is a tissue-specific regulator of
      glucocorticoid responses, inducing the interconversion of inactive and active
      glucocorticoids. OBJECTIVE: We analysed the expression and distribution patterns
      of 11beta-HSD1, 11beta-HSD2, and steroidogenic enzymes in normal and allergic
      nasal mucosa, and cytokine-driven regulation of their expression. The production
      levels of cortisol in normal, allergic nasal mucosa and in cultured epithelial
      cells stimulated with cytokines were also determined. METHODS: The expression
      levels of 11beta-HSD1, 11beta-HSD2, steroidogenic enzymes (CYP11B1, CYP11A1), and
      cortisol in normal, mild, and moderate/severe persistent allergic nasal mucosa
      were assessed by real-time PCR, Western blot, immunohistochemistry, and ELISA.
      The expression levels of 11beta-HSD1, 11beta-HSD2, CYP11B1, CYP11A1, and cortisol
      were also determined in cultured nasal epithelial cell treated with IL-4, IL-5,
      IL-13, IL-17A, and IFN-gamma. Conversion ratio of cortisone to cortisol was
      evaluated using siRNA technique, 11beta-HSD1 inhibitor, and the measurement of
      11beta-HSD1 activity. RESULTS: The expression levels of 11beta-HSD1, CYP11B1, and
      cortisol were up-regulated in mild and moderate/severe persistent allergic nasal
      mucosa. By contrast, 11beta-HSD2 expression was decreased in allergic nasal
      mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A,
      11beta-HSD1 expression and activity increased in parallel with the expression
      levels of CYP11B1 and cortisol, but the production of 11beta-HSD2 decreased.
      CYP11A1 expression level was not changed in allergic nasal mucosa or in response
      to stimulation with cytokines. SiRNA technique or the measurement of 11beta-HSD1
      activity showed that nasal epithelium activates cortisone to cortisol in a 11beta
      HSD-dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate
      that the localized anti-inflammatory effects of glucocorticoids are regulated by
      inflammatory cytokines, which can modulate the expression of 11beta-HSD1, 11beta
      HSD2, and CYP11B1, and by the intracellular concentrations of bioactive
      glucocorticoids.

PMID- 24447084
TI  - Quantification of circulating house dust mite-specific IL-4- and IL-13-secreting
      T cells correlates with rhinitis severity in asthmatic children and varies with
      the seasons.
AB  - BACKGROUND: Defining suitable markers to diagnose and monitor allergy and its
      severity is essential to correctly assign patients for specific immunotherapy.
      Circulating levels of specific IgE are good markers of sensitization, but not of
      clinically symptomatic allergy. OBJECTIVE: To quantify circulating interleukin
      (IL)-4- and IL-13-secreting T cells specific for house dust mite (HDM) in
      children presenting HDM-allergic asthma associated or not with rhinitis and
      correlate results with clinical symptoms. METHODS: We analysed 26 children with
      HDM respiratory disease (allergic rhinitis and asthma) together with six children
      with non-allergic asthma. Peripheral blood mononuclear cells were stimulated with
      HDM extract in a 24-h ELISpot assay to quantify the number of HDM-specific IL-4-
      and IL-13-secreting T cells. Asthma severity and control, and rhinitis severity
      were scored according to the Global Initiative for Asthma (GINA) and the Allergic
      Rhinitis and its Impact on Asthma (ARIA) Guidelines. RESULTS: The number of HDM
      specific IL-4- and IL-13-secreting T cells was higher in patients with allergic
      asthma as compared to patients with non-allergic asthma. It varied with the
      season of blood sampling with two peaks in the fall and early spring.
      Independently of the season, the number of HDM-specific IL-4-secreting T cells
      correlated with rhinitis severity (OR = 2; 95% IC:1.1-3.8; P = 0.04). CONCLUSIONS
      AND CLINICAL RELEVANCE: Allergen-specific IL-4- and IL-13-producing T cells were
      only detected in HDM-allergic asthmatic children (not in patients with non
      allergic asthma). Their numbers correlated with clinical severity of allergic
      rhinitis.

PMID- 24447083
TI  - Frequent exacerbators--a distinct phenotype of severe asthma.
AB  - BACKGROUND: Exacerbations represent a major source of morbidity and mortality in
      asthma and are a prominent feature of poorly controlled, difficult-to-treat
      disease. OBJECTIVE: The goal of our study was to provide a detailed
      characterization of the frequent exacerbator phenotype and to identify risk
      factors associated with frequent and seasonal exacerbations. METHODS: Ninety
      three severe asthmatics (SA) and 76 mild-to-moderate patients (MA) were screened
      and prospectively followed up for 1 year (NCT00555607). Medical history, baseline
      clinical data and biomarkers were used to assess risk factors for frequent
      exacerbations. RESULTS: During the study, 104 exacerbations were recorded in the
      SA group and 18 in the MA. Frequent exacerbators were characterized by use of
      higher doses of inhaled (1700 vs. 800 MUg) and oral (6.7 vs. 1.7 mg)
      glucocorticosteroids, worse asthma control (ACQ score 2.3 vs. 1.4), lower quality
      of life (SGRQ score 48.5 vs. 33.3), higher sputum eosinophils (25.7% vs. 8.2%)
      and a more rapid decline in FEV1 /FVC ratio (-0.07 vs. -0.01 DeltaFEV1 /FVC,
      frequent vs. non-frequent, respectively, P < 0.05). Exhaled NO > 45 p.p.b. and a
      history of smoking were associated with an increased risk of frequent
      exacerbations (odds ratios: 4.32 and 2.90 respectively). CONCLUSION AND CLINICAL
      RELEVANCE: We were able to distinguish and characterize a subphenotype of asthma
      subjects--frequent exacerbators--who are significantly more prone to
      exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at
      increased risk of frequent exacerbations and require careful monitoring in
      clinical practice.

PMID- 24447085
TI  - Vitamin D-binding protein haplotype is associated with hospitalization for RSV
      bronchiolitis.
AB  - BACKGROUND: Between 75 000 and 125 000 U.S. infants are hospitalized for
      respiratory syncytial virus (RSV) bronchiolitis every year. Up to half will be
      diagnosed with asthma in later childhood. Vitamin D deficiency has been
      associated with susceptibility to asthma and respiratory infections. Measured
      vitamin D is largely bound to vitamin D-binding protein (VDBP); VDBP levels are
      influenced by its gene (GC) haplotype. OBJECTIVE: We assessed the relationship
      between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and
      GC2, and RSV bronchiolitis susceptibility and subsequent asthma. METHODS: We
      retrospectively recruited 198 otherwise healthy children (93% White) hospitalized
      for severe RSV bronchiolitis in Boston and 333 parents into a follow-up study to
      assess asthma diagnosis. Data were analysed using family-based genetic
      association tests. We independently validated our results in 465 White children
      hospitalized with RSV bronchiolitis and 930 White population controls from the
      Netherlands. RESULTS: The rs7041_C allele (denoting haplotype GC1s) was
      overtransmitted (P = 0.02, additive model) in the entire Boston cohort, in Whites
      (P = 0.03), and especially in children subsequently diagnosed with asthma (P =
      0.006). The GC1f haplotype was undertransmitted in the asthma subgroups (all
      races and White, both P < 0.05). The rs7041_C allele was also more frequent in
      the RSV bronchiolitis group compared with controls (OR 1.12, 95% CI 1.02, 1.4, P
      = 0.03) in the Netherlands, especially in mechanically ventilated patients (P =
      0.009). CONCLUSION AND CLINICAL RELEVANCE: GC1s haplotype carriage may increase
      the risk of RSV bronchiolitis in infancy and subsequent asthma development. The
      GC1s haplotype is associated with higher VDBP levels, resulting in less freely
      available vitamin D. KEY MESSAGES: Vitamin D-binding protein (VDBP) haplotypes
      influence free vitamin D levels. We report an association between a VDBP
      haplotype and hospitalization for RSV bronchiolitis in infancy in two independent
      cohorts.

PMID- 24447089
TI  - Functional role of evolutionarily highly conserved residues, N-glycosylation
      level and domains of the Leishmania miltefosine transporter-Cdc50 subunit.
AB  - Cdc50 (cell-cycle control protein 50) is a family of conserved eukaryotic
      proteins that interact with P4-ATPases (phospholipid translocases). Cdc50
      association is essential for the endoplasmic reticulum export of P4-ATPases and
      proper translocase activity. In the present study, we analysed the role of
      Leishmania infantum LiRos3, the Cdc50 subunit of the P4-ATPase MLF (miltefosine)
      transporter [LiMT (L. infantum MLF transporter)], on trafficking and complex
      functionality using site-directed mutagenesis and domain substitution. We
      identified 22 invariant residues in the Cdc50 proteins from L. infantum, human
      and yeast. Seven of these residues are found in the extracellular domain of
      LiRos3, the conservation of which is critical for ensuring that LiMT arrives at
      the plasma membrane. The substitution of other invariant residues affects complex
      trafficking to a lesser extent. Furthermore, invariant residues located in the N
      terminal cytosolic domain play a role in the transport activity. Partial N
      glycosylation of LiRos3 reduces MLF transport and total N-deglycosylation
      completely inhibits LiMT trafficking to the plasma membrane. One of the N
      glycosylation residues is invariant along the Cdc50 family. The transmembrane and
      exoplasmic domains are not interchangeable with the other two L. infantum Cdc50
      proteins to maintain LiMT interaction. Taken together, these findings indicate
      that both invariant and N-glycosylated residues of LiRos3 are implicated in LiMT
      trafficking and transport activity. 

PMID- 24447087
TI  - Human IgE against the major allergen Bet v 1--defining an epitope with limited
      cross-reactivity between different PR-10 family proteins.
AB  - BACKGROUND: The interaction between IgE and allergen is a key event at the
      initiation of an allergic response, and its characteristics have substantial
      effects on the clinical manifestation. Despite this, the molecular details of the
      interaction between human IgE and the major birch allergen Bet v 1, one of the
      most potent tree allergens, still remain poorly investigated. OBJECTIVE: To
      isolate Bet v 1-specific human monoclonal IgE and characterize their interaction
      with the allergen. METHODS: Recombinant human IgE were isolated from a
      combinatorial antibody fragment library and their interaction with Bet v 1
      assessed using various immunological assays. The structure of one such IgE in the
      single-chain fragment variable format was determined using X-ray crystallography.
      RESULTS: We present four novel Bet v 1-specific IgE, for one of which we solve
      the structure, all with their genetic origin in the IGHV5 germline gene, and
      demonstrate that they target two non-overlapping epitopes on the surface of Bet v
      1, thereby fulfilling the basic criteria for FcepsilonRI cross-linkage. We
      further define these epitopes and for one epitope pinpoint single amino acid
      residues important for the interaction with human IgE. This provides a potential
      explanation, at the molecular level, for the differences in recognition of
      isoforms of Bet v 1 and other allergens in the PR-10 protein family displayed by
      IgE targeting this epitope. Finally, we present the first high-resolution
      structure of a human allergen-specific IgE fragment in the single-chain fragment
      variable (scFv) format. CONCLUSIONS AND CLINICAL RELEVANCE: We here display the
      usefulness of allergen-specific human monoclonal IgE as a tool in studies of the
      crucial molecular interaction taking place at the initiation of an allergic
      response. Such studies may aid us in development of better diagnostic tools and
      guide us in the development of new therapeutic compounds.

PMID- 24447090
TI  - Associations of the Baltic Sea diet with obesity-related markers of inflammation.
AB  - INTRODUCTION: Inflammation is an important contributor to the development of
      chronic diseases. We examined whether a healthy Nordic diet, also called the
      Baltic Sea diet, associates with lower concentrations of inflammatory markers.
      METHODS: We used two independent cross-sectional studies: the DILGOM study
      including Finnish participants aged 25-74 years (n = 4579), and the Helsinki
      Birth Cohort Study including individuals born at Helsinki University Central
      Hospital between 1934 and 1944 and who participated in a clinical examination in
      2001-2004 (n = 1911). Both studies measured anthropometrics, drew blood, and
      assessed concentrations of leptin, high-molecular-weight adiponectin, tumor
      necrosis factor alpha, interleukin 6, and high-sensitivity C-reactive protein (hs
      CRP). A food frequency questionnaire was used to measure dietary intake over the
      past year and calculate the Baltic Sea Diet Score (BSDS). RESULTS: In both
      studies, linear regression adjusting for age, sex, energy intake, lifestyle
      factors, obesity, statin medication, and upstream inflammatory markers revealed
      an inverse association between the BSDS and hs-CRP concentrations (P < 0.01).
      Especially, high intake of Nordic fruits and cereals, low intake of red and
      processed meat, and moderate intake of alcohol contributed to the emerged
      association (P < 0.05). The BSDS did not associate with other inflammatory
      markers. CONCLUSION: The Baltic Sea diet is associated with lower hs-CRP
      concentrations.

PMID- 24447086
TI  - Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides
      lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell
      responses via blocking antibodies in a murine model for birch pollen allergy.
AB  - BACKGROUND: Vaccines consisting of allergen-derived peptides lacking IgE
      reactivity and allergen-specific T cell epitopes bound to allergen-unrelated
      carrier molecules have been suggested as candidates for allergen-specific
      immunotherapy. OBJECTIVE: To study whether prophylactic and therapeutic
      vaccination with carrier-bound peptides from the major birch pollen allergen Bet
      v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T
      cell responses. METHODS: Three Bet v 1-derived peptides, devoid of Bet v 1
      specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide
      to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were
      immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet
      v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and
      cytokine responses to Bet v 1, KLH, and the peptides were studied in
      proliferation assays. The effects of peptide-specific and allergen-specific
      antibodies on T cell responses and allergic lung inflammation were studied using
      specific antibodies. RESULTS: Prophylactic and therapeutic vaccination with
      carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response
      without priming/boosting of Bet v 1-specific T cells. Prophylactic and
      therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific
      antibodies which suppressed Bet v 1-specific T cell responses and allergic lung
      inflammation. CONCLUSION AND CLINICAL RELEVANCE: Vaccination with carrier-bound
      allergen-derived peptides lacking allergen-specific T cell epitopes induces
      allergen-specific IgG antibodies which suppress allergen-specific T cell
      responses and allergic lung inflammation.

PMID- 24447091
TI  - Identification and characterization of the phenolic glycosides of Lagenaria
      siceraria Stand. (bottle gourd) fruit by liquid chromatography-tandem mass
      spectrometry.
AB  - Bottle gourd, Lagenaria siceraria Stand. (Cucurbitaceae), fruit is used in folk
      medicines and for culinary purposes in Asia. The phenolics of bottle gourd fruit
      were investigated qualitatively by LC-MS(n). Twenty-two phenolic glycosides were
      detected and characterized on the basis of their unique fragmentation pattern in
      the negative ion mode tandem MS spectra. Twenty of them were extracted for the
      first time from this source, and twelve of them have not been reported previously
      in nature. It was also possible to distinguish between the individual classes of
      isobaric phenolic glycosides by tandem and high-resolution mass spectrometry. In
      this study we also discuss the mass spectrometric fragmentation mechanism of 6
      (hydroxycinnamoyl)glucoses. This is the first report of the full characterization
      of phenolic glycosides of bottle gourd fruit by LC-MS2-4.

PMID- 24447092
TI  - Development and implementation of a formalized geriatric surgery curriculum for
      general surgery residents.
AB  - Despite the growth of the elderly population, most surgical training programs
      lack formalized geriatric education. The authors' aim was to implement a
      formalized geriatric surgery curriculum at an academic medical center. Surgery
      residents were surveyed on attitudes toward the care of elderly patients and the
      importance of various geriatric topics to daily practice. A curriculum consisting
      of 16 didactic sessions was created with faculty experts moderating. After
      curriculum completion, residents were surveyed to assess curriculum impact.
      Residents expressed increased comfort in accessing community resources. A greater
      percentage of residents recognized the significance of delirium and acute renal
      failure in elderly patients. Implementing a geriatric surgery curriculum geared
      toward surgery residents is feasible and can increase resident comfort with
      multidisciplinary care and recognition of clinical conditions pertinent to
      elderly surgical patients. This initiative also provided valuable experience for
      geriatric surgery curriculum development. 

PMID- 24447093
TI  - Chronic kidney disease is independently associated with alterations in left
      atrial function.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased
      cardiovascular morbidity and mortality; hence detection of early cardiovascular
      involvement in CKD is important to prevent future adverse cardiovascular events.
      Left atrial (LA) enlargement and dysfunction has been reported in end stage renal
      disease. However, there is a paucity of published data regarding the evaluation
      of LA function in CKD using noninvasive imaging parameters. In this study, we
      evaluated biplane LA volume as well as LA function (LA global systolic strain
      (GS) and strain rate [SR]) in stage 3 CKD patients (eGFR 30-59 mL/min per 1.73
      m(2) ) to determine if LA function parameters are more significantly altered by
      the presence of CKD in addition to changes due to hypertension alone. METHODS:
      Thirty-three CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) with hypertension
      were compared to 33 normal controls and 34 hypertensive (HT) subjects with normal
      renal function; all participants underwent a detailed transthoracic
      echocardiogram. Indexed biplane LA volume (LAVI), LA segmental function, and GS
      and SR (systolic, early, and late diastole) derived from tissue Doppler imaging
      (TDI) were measured. Univariate predictors of LA strain were determined. Multiple
      logistic regression analysis was used to examine the effect of patient group
      (i.e. CKD) on GS and SR as well as LAVI. RESULTS: Left atrial volume indexed was
      significantly increased in both the HT and CKD with HT group compared to normal
      controls (28 +/- 9 mL/m(2) vs. 28 +/- 9 mL/m(2) vs. 23 +/- 5 mL/m(2) ,
      respectively, P = 0.02). However, LAVI was similar in the HT and CKD with HT
      group (28 +/- 9 mL/m(2) vs. 28 +/- 9 mL/m(2) ; P = NS). LA GS and SR were reduced
      in both the CKD with HT and HT group, compared to controls. However, a
      significantly lower LA GS was present in the CKD with HT group (Controls vs. HT
      vs. CKD with HT: 54.9 +/- 14.5% vs. 34.5 +/- 6.2% vs. 25.7 +/- 9.3%,
      respectively; P = 0.001). To examine the effect of group, (i.e. presence of CKD)
      multiple logistic regression analysis was performed with univariate predictors
      including indexed left ventricular mass (LVMI), LV diastolic grade, LAVI, peak A
      wave velocity, beta-blocker therapy, GS and SR; this demonstrated that CKD had an
      independent effect on LA GS and SR (systolic, early, and late diastole). GS
      demonstrated moderate correlation with systolic blood pressure (r = -0.5, P =
      0.01), diastolic grade (r = -0.5, P = 0.01), E' velocity (r = 0.6, P = 0.0001),
      peak A velocity (r = -0.5, P = 0.004), and LAVI (r = -0.6, P = 0.002).
      CONCLUSIONS: Left atrial dysfunction is evident in stage 3 CKD with associated LA
      enlargement. This study demonstrates that LA GS and SR were reduced in the CKD
      group despite similar LAVI in the CKD with HT and HT group. Hence LA GS and SR
      may be a more sensitive noninvasive tool to detect cardiovascular involvement in
      CKD.

PMID- 24447094
TI  - PPARalpha activation sensitizes cancer cells to epigallocatechin-3-gallate (EGCG)
      treatment via suppressing heme oxygenase-1.
AB  - Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green
      tea, is a potent antioxidant that may have potential therapeutic applications for
      the treatment of many disorders, including cancer. Peroxisome proliferator
      activated receptor-alpha (PPARalpha) has been shown to play a key role in diverse
      metabolic and cellular functions. PPARalpha modulates target gene expression by
      binding to specific regions on the DNA of target genes. The effects and
      mechanisms of PPARalpha activation on EGCG efficacy have not yet been analyzed in
      cancer cells. We found that when cancer cells were exposed to EGCG, the
      expression of PPARalpha was increased at the protein level in a dose-dependent
      manner. The PPARalpha agonist clofibrate blocked cytoprotective heme oxygenase-1
      (HO-1) induction and sensitized multiple types of cancer cells to EGCG-induced
      cell death. Conversely, the PPARalpha inhibitor G6471 and PPARalpha siRNA
      increased HO-1 expression. Electro-mobility shift assays (EMSA) and in vivo
      chromatin immunoprecipitation (ChIP) confirmed that PPARalpha interacts with the
      peroxisome proliferator-responsive element of the HO-1 promoter. Moreover, cell
      death induced by EGCG plus clofibrate was partially reversed by HO-1
      overexpression in PANC1 cells. These results indicate that PPARalpha is a direct
      and negative regulator of HO-1 induced by EGCG and confers cell susceptibility to
      EGCG. 

PMID- 24447099
TI  - Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of
      structure, integrity, and connectivity.
AB  - OBJECTIVE: Thalamic abnormality in temporal lobe epilepsy (TLE) is well known
      from imaging studies, but evidence is lacking regarding connectivity profiles of
      the thalamus and their involvement in the disease process. We used a novel
      multisequence magnetic resonance imaging (MRI) protocol to elucidate the
      relationship between mesial temporal and thalamic pathology in TLE. METHODS: For
      23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for
      analysis of tissue structure), diffusion tensor imaging (tissue connectivity),
      and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used
      connectivity-based segmentation to determine connectivity patterns of thalamus to
      ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral,
      precentral, and temporal). We subsequently determined volumes, mean tractography
      streamlines, and mean T1 and T2 relaxometry values for each thalamic segment
      preferentially connecting to a given cortical region, and of the hippocampus and
      entorhinal cortex. RESULTS: As expected, patients had significant volume
      reduction and increased T2 relaxation time in ipsilateral hippocampus and
      entorhinal cortex. There was bilateral volume loss, mean streamline reduction,
      and T2 increase of the thalamic segment preferentially connected to temporal
      lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with
      no evidence of significant change in any other thalamic segments. Left and right
      thalamotemporal segment volume and T2 were significantly correlated with volume
      and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic),
      mesial temporal structures. SIGNIFICANCE: These convergent and robust data
      indicate that thalamic abnormality in TLE is restricted to the area of the
      thalamus that is preferentially connected to the epileptogenic temporal lobe. The
      degree of thalamic pathology is related to the extent of mesial temporal lobe
      damage in TLE.

PMID- 24447098
TI  - Protein and enzyme gated supramolecular disassembly.
AB  - An amphiphilic nanoassembly was designed to respond to the concurrent presence of
      a protein and an enzyme. We present herein a system, where in the presence of
      these two stimuli supramolecular disassembly and molecular release occur. This
      molecular release arises in the form a fluorescence response that has been shown
      to be specific. We also show that this system can be modified to respond only if
      light stimulus is also present in addition to the protein and the enzyme.
      Demonstration of such supramolecular disassembly principles could have broad
      implications in a variety of biological applications. 

PMID- 24447104
TI  - Hybridization between periodic mesoporous organosilica and a Ru(II) polypyridyl
      complex with phosphonic acid anchor groups.
AB  - A new method for the hybridization of a ruthenium(II) polypyridyl complex
      ([Ru(bpy)2((CH2PO3H2)2-bpy)](2+) (RuP2(2+): bpy =2,2'-bipyridine; (CH2PO3H2)2-bpy
      =2,2'-bipyridine-4,4'di(metylphosphonic acid)) with biphenylene-bearing periodic
      mesoporous organosilica (Bp-PMO made from 4,4'bis(triethoxysilyl)biphenyl
      [(C2H5O)3Si-(C6H4)2-Si(OC2H5)3]) was developed. Efficient and secure fixation of
      the ruthenium(II) complex with methylphosphonic acid groups (RuP2(2+)) in the
      mesopores of Bp-PMO occurred. This method introduced up to 660 MUmol of RuP2(2+)
      in 1 g of Bp-PMO. Two modes of adsorption of RuP2(2+) in the mesopores of Bp-PMO
      were observed: one is caused by the chemical interaction between the
      methylphosphonic acid groups of RuP2(2+) and the silicate moieties of Bp-PMO and
      the other is attributed to aggregation of the RuP2(2+) complexes. In the case of
      the former mode, adsorbed RuP2(2+) (up to 80-100 MUmol g(-1)) did not detach from
      Bp-PMO after washing with acetonitrile, dimethylformamide, or even water.
      Emission from the excited biphenylene (Bp) units was quantitatively quenched by
      the adsorbed RuP2(2+) molecules in cases where more than 60 MUmol g(-1) of
      RuP2(2+) was adsorbed, and emission from RuP2(2+) was observed. Quantitative
      emission measurements indicated that emission from approximately 100 Bp units can
      be completely quenched by only one RuP2(2+) molecule in the mesopore, and photons
      absorbed by approximately 400 Bp units are potentially accumulated in one
      RuP2(2+) molecule. 

PMID- 24447103
TI  - Profiling the genes affected by pathogenic TDP-43 in astrocytes.
AB  - Mutation in TAR DNA binding protein 43 (TDP-43) is a causative factor of
      amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
      Neurodegeneration may not require the presence of pathogenic TDP-43 in all types
      of relevant cells. Rather, expression of pathogenic TDP-43 in neurons or
      astrocytes alone is sufficient to cause cell-autonomous or non-cell-autonomous
      neuron death in transgenic rats. How pathogenic TDP-43 in astrocytes causes non
      cell-autonomous neuron death, however, is not clear. Here, we examined the effect
      of pathogenic TDP-43 on gene expression in astrocytes. Microarray assay revealed
      that pathogenic TDP-43 in astrocytes preferentially altered expression of the
      genes encoding secretory proteins. Whereas neurotrophic genes were down
      regulated, neurotoxic genes were up-regulated. Representative genes Lcn2 and
      chitinase-3-like protein 1 were markedly up-regulated in astrocytes from primary
      culture and intact transgenic rats. Furthermore, synthetic chitinase-3-like
      protein 1 induced neuron death in a dose-dependent manner. Our results suggest
      that TDP-43 pathogenesis is associated with the simultaneous induction of
      multiple neurotoxic genes in astrocytes, which may synergistically produce
      adverse effects on neuronal survival and contribute to non-cell-autonomous neuron
      death. Restricted expression of pathogenic TDP-43 in astrocytes causes non-cell
      autonomous motor neuron death in transgenic rats. As revealed by microarray
      assay, pathogenic TDP-43 in astrocytes preferentially altered expression of the
      genes encoding secretory proteins. Whereas neurotrophic genes were down
      regulated, neurotoxic genes were up-regulated. Therefore, TDP-43 pathogenesis is
      associated with simultaneous induction of neurotoxic genes and repression of
      neurotrophic genes in astrocytes. 

PMID- 24447105
TI  - Current evidence for transurethral en bloc resection of non-muscle-invasive
      bladder cancer.
AB  - INTRODUCTION: Despite today's standard procedure for staging and treating non
      muscle-invasive bladder cancer by transurethral resection via a wire loop
      (TURBT), several other publications have dealt with a different concept of en
      bloc resection of bladder tumors using different energy sources. MATERIAL AND
      METHODS: MEDLINE and the Cochrane central register were searched for the
      following terms: en bloc, mucosectomy, laser, resection, ablation, Neodym,
      Holmium, Thulium, transitional cell carcinoma. RESULTS: Fourteen research
      articles dealing with en bloc resection of non-muscle-invasive bladder cancer
      could be identified (modified resection loops: six, laser: six, waterjet
      hydrodissection: two). CONCLUSION: En bloc resection of bladder tumors >1 cm can
      be performed safely with very low complication rates independent of the power
      source. By using laser, complication rates might even be decreased, based on
      their good hemostatic effect and by avoiding the obturator nerve reflex. A
      further advantage seems to be accurate pathologic staging of en bloc tumors.
      Randomized controlled trials are still needed to support the assumed advantages
      of en bloc resection over the standard TURBT with regard to primary targets:
      First-time clearance of disease, accurate staging and recurrence rates.

PMID- 24447106
TI  - Sensor-based surgical activity recognition in unconstrained environments.
AB  - INTRODUCTION: Automatic surgical activity recognition in the operating room (OR)
      is mandatory to enable assistive surgical systems to manage the information
      presented to the surgical team. Therefore the purpose of our study was to develop
      and evaluate an activity recognition model. MATERIAL AND METHODS: The system was
      conceived as a hierarchical recognition model which separated the recognition
      task into activity aspects. The concept used radio frequency identification
      (RFID) for instrument recognition and accelerometers to infer the performed
      surgical action. Activity recognition was done by combining intermediate results
      of the aspect recognition. A basic scheme of signal feature generation,
      clustering and sequence learning was replicated in all recognition subsystems.
      Hidden Markov models (HMM) were used to generate probability distributions over
      aspects and activities. Simulated functional endoscopic sinus surgeries (FESS)
      were used to evaluate the system. RESULTS AND DISCUSSION: The system was able to
      detect surgical activities with an accuracy of 95%. Instrument recognition
      performed best with 99% accuracy. Action recognition showed lower accuracies with
      81% due to the high variability of surgical motions. All stages of the
      recognition scheme were evaluated. The model allows distinguishing several
      surgical activities in an unconstrained surgical environment. Future improvements
      could push activity recognition even further.

PMID- 24447107
TI  - Clinical experience with a simple retraction device in single-port laparoscopic
      cholecystectomy: technical description and initial results.
AB  - BACKGROUND: Performing single-port laparoscopic cholecystectomy (SPLC) is
      challenging as triangulation is limited and the critical view is difficult to
      obtain. We present our initial experience using a simple retraction device to
      reduce these problems. MATERIAL AND METHODS: In January 2012 a novel lifter was
      introduced at our department and subsequently used in SPLC for suspension of the
      gallbladder. Perioperative data were collected prospectively. In addition, all
      videos were reviewed to assess any adverse events caused by the lifter. RESULTS:
      Thirty (20 female and 10 male) patients at a median age of 48.4 years (range: 23
      83) were operated using this novel retraction device. Median BMI accounted for
      26.0 kg/m(2) (median; range: 14.0-36.9). Retraction of the gallbladder using the
      lifter was possible in all patients. In four cases (13.3 %) spillage of bile
      caused by the lifter was recorded. In addition, perforation of the gallbladder
      was seen once (3.3 %), caused by electrocautery. No inflammation, induration or
      visible scars were seen in the right upper quadrant at six weeks postoperatively
      in any patient. CONCLUSIONS: Gallbladder retraction in SPLC using this novel
      device is feasible and safe without leaving any apparent scar. Rate of bile
      spillage is (at least) comparable to that reported for conventional laparoscopic
      cholecystectomy.

PMID- 24447108
TI  - Who described Civatte bodies?
AB  - Eosinophilic apoptotic (necrotic) keratinocytes in the lower epidermis and at the
      dermoepidermal junction are a feature of many interface dermatoses but are most
      reliably found in lichen planus. These structures are universally known as
      Civatte bodies. Nonetheless, they were first described by Raymond Sabouraud in
      1912. Even after Achille Civatte discussed and beautifully illustrated them a
      decade later, it took until the late 1960s for the term Civatte body to win
      acceptance. 

PMID- 24447109
TI  - Induced pluripotent stem cells from human placental chorion for perinatal tissue
      engineering applications.
AB  - The reliable derivation of induced pluripotent stem cells (iPSCs) from a
      noninvasive autologous source at birth would facilitate the study of patient
      specific in vitro modeling of congenital diseases and would enhance ongoing
      efforts aimed at developing novel cell-based treatments for a wide array of fetal
      and pediatric disorders. Accordingly, we have successfully generated iPSCs from
      human fetal chorionic somatic cells extracted from term pregnancies by ectopic
      expression of OCT4, SOX2, KLF4, and cMYC. The isolated parental somatic cells
      exhibited an immunophenotypic profile consistent with that of chorionic
      mesenchymal stromal cells (CMSCs). CMSC-iPSCs maintained pluripotency in feeder
      free systems for more than 15 passages based on morphology, immunocytochemistry,
      and gene expression studies and were capable of embryoid body formation with
      spontaneous trilineage differentiation. CMSC-iPSCs could be selectively
      differentiated in vitro into various germ layer derivatives, including neural
      stem cells, beating cardiomyocytes, and definitive endoderm. This study
      demonstrates the feasibility of term placental chorion as a novel noninvasive
      alternative to dermal fibroblasts and cord blood for human perinatal iPSC
      derivation and may provide additional insights regarding the reprogramming
      capabilities of extra-embryonic tissues as they relate to developmental ontogeny
      and perinatal tissue engineering applications. 

PMID- 24447110
TI  - Clinical evaluation of glycolic acid chemical peeling in patients with acne
      vulgaris: a randomized, double-blind, placebo-controlled, split-face comparative
      study.
AB  - BACKGROUND: Glycolic acid (GA) peels are frequently performed as adjuvants to the
      treatment of facial acne. There have been few clinical trials reported of GA
      peels for acne in people with darker skin. OBJECTIVES: To determine the safety
      and efficacy of GA peels in the treatment of moderate acne vulgaris in Asian
      skin. METHODS: In this prospective, randomized, double-blind, placebo-controlled,
      split-face clinical trial, 26 patients with moderate acne were treated with 40%
      GA (pH 2.0) on half of the face and placebo on the other half. The procedure was
      performed five times at 2-week intervals. RESULTS: The GA sides had statistically
      significant reductions in acne lesions at each time point from baseline values.
      There were statistically significant differences between the GA and placebo
      sides. The GA sides had better responses for noninflammatory lesions than for
      inflammatory lesions. In bioengineering measurements, sebum levels were
      statistically significantly reduced after the initiation of therapy on both sides
      at weeks 8 and 10, but there were no statistically significant differences
      between the two sides. CONCLUSION: Forty percent GA peels significantly improved
      moderate acne in this study. It is effective and safe in Asians.

PMID- 24447111
TI  - Development of a drug delivery system for the inner ear using poly(amino acid)
      based nanoparticles.
AB  - CONTEXT: Local delivery systems for treatment of intractable inner ear disorders
      have been attempted by many investigators. OBJECTIVE: To evaluate the
      permeability and safety of a drug delivery system for the inner ear using a
      poly(2-hydroxyethyl aspartamide) (PHEA) polymersome. MATERIALS AND METHODS: One
      month-old male C57/BL6 mice were used. We administered the same amount of the
      fluorescent dye, Nile red, into the middle ear in two forms: loaded in PHEA
      polymersomes (NP group) or diluted in ethanol (NR group). At 1 day after
      administration, we harvested the cochlea and counted visible red particles in the
      tissues of cochlea under confocal microscopy and compared the groups. In a safety
      evaluation, 1 week after the same surgery, we conducted hearing tests and
      histological evaluations of the bulla and cochlea, and compared the results with
      those of the sham operation and negative control groups. RESULTS: In terms of
      permeability, the number of red particles in the organ of Corti was increased
      significantly in the NP group, and three subjects in the NP group showed uptake
      of red particles in inner hair cells. However, there was no statistically
      significant difference in the observations in the lateral wall or modiolus. In
      safety tests, the NP and sham-operation groups showed decreased DPOAE responses
      and mildly swollen middle ear mucosa, compared with the negative control group,
      which was thought to be the result of postoperative changes. CONCLUSIONS: PHEA
      nanoparticles may have utility as a drug carrier into the inner ear in terms of
      both permeability and safety.

PMID- 24447112
TI  - Effect of tumour necrosis factor-alpha inhibitor on serum level of dickkopf-1
      protein and bone morphogenetic protein-7 in ankylosing spondylitis patients with
      high disease activity.
AB  - OBJECTIVES: To examine changes in serum levels of the bone remodelling molecules
      dickkopf-1 (Dkk-1), sclerostin, wingless-type protein-3a (Wnt-3a), and bone
      morphogenetic protein-7 (BMP-7) during 6 months of anti-tumour necrosis factor
      (anti-TNF) treatment in ankylosing spondylitis (AS) patients with high disease
      activity. METHOD: We included 40 patients with axial AS: 20 patients with high
      disease activity were assigned to treatment with TNF inhibitor and 20 with low
      disease activity were assigned to non-steroidal anti-inflammatory drug (NSAID)
      treatment. Markers of bone remodelling and inflammation were assessed at baseline
      and after 6 months. RESULTS: In the TNF inhibitor-treated group Dkk-1 decreased
      significantly from 196.8 pg/mL [95% confidence interval (CI) 94.1-399.0] to 116.3
      pg/mL (95% CI 38.0-301.6) and BMP-7 increased significantly from 1.4 pg/mL (95%
      CI 0-23.0) to 20.3 pg/mL (95% CI 4.9-41.3). There was a significant negative
      correlation between Dkk-1 and BMP-7 at 6 months (r = -0.64, p = 0.004) in this
      group. Non-parametric regression analysis adjusted for disease duration, age,
      sex, baseline modified Stoke's Ankylosing Spondylitis Spine Score (mSASSS), and
      baseline C-reactive protein (CRP) confirmed a statistically significant effect of
      treatment on time-related changes of Dkk-1 and BMP-7. Erythrocyte sedimentation
      rate (ESR), CRP, and also the Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI) score decreased significantly in the anti-TNF-treated group.
      CONCLUSIONS: Among the potential biomarkers of bone remodelling in AS, Dkk-1 and
      BMP-7 displayed significant time alterations and correlative interactions during
      anti-TNF treatment.

PMID- 24447113
TI  - Relation between QRS duration and atrial synchronicity in patients with systolic
      heart failure.
AB  - OBJECTIVES: The association of QRS duration (QRSd) with ventricular dyssynchrony
      is well-known in systolic heart failure (HF). However, there are no data
      regarding the relationship between QRSd and atrial dyssynchrony in patients with
      HF. We aimed to investigate the association of QRSd with intra-atrial and inter
      atrial dyssynchrony in patients with systolic HF by using color tissue Doppler
      imaging (TDI). METHODS: The study consisted of 70 systolic HF patients and 35
      healthy controls. According to QRSd, HF patients were categorized into 2
      subgroups as narrow QRS (n = 35) and wide QRS (n = 35) groups. Time intervals
      between the onset of P-wave and the onset of A-wave on color TDI from the right
      atrium (P-RA), inter-atrial septum (P-IAS) and left atrium (P-LA) were measured.
      Atrial dyssynchrony was defined as differences between P-RA and P-IAS (RA
      dyssynchrony), between P-LA and P-IAS (LA dyssynchrony) and between P-RA and P-LA
      (inter-atrial dyssynchrony). RESULTS: In patients with either HF groups, we
      observed significant impairment in intra-atrial and inter-atrial synchronicity
      compared with the controls (P < 0.001). Moreover, LA, RA and inter-atrial
      synchrony were found to be significantly impaired in the wide QRS group compared
      to narrow QRS group. There was also a positive and strong correlation between
      atrial and ventricular dyssynchrony parameters. In stepwise multivariate
      analysis, QRSd was found to be the independent predictor of intra-atrial and
      inter-atrial dyssynchrony in systolic HF. CONCLUSION: Among patients with
      systolic HF, prolonged QRSd is associated with impaired intra-atrial and inter
      atrial synchrony. Atrial and ventricular dyssynchrony parameters were well
      correlated with each other.

PMID- 24447114
TI  - Predictors of clinical effectiveness of Hymenoptera venom immunotherapy.
AB  - BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated
      with a variety of risk factors, of which the relative importance is unknown.
      OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase
      concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with
      the frequency of objective systemic reactions during in-hospital sting challenge
      (SC). METHODS: In this observational retrospective study, we enrolled 1532
      patients (1609 cases due to double SC) with established honeybee or vespid venom
      allergy who had undergone VIT and a subsequent SC. Data were collected on various
      putative risk factors. Adult-onset MIS and/or a BTC > 20.0 MUg/L was defined as
      clinical indicators of systemic mastocytosis. Relative rates were calculated with
      logistic regression models. RESULTS: Ninety-eight patients (6.4%) presented with
      MIS and/or BTC > 20.0 MUg/L. 104 cases (6.5%) developed objective generalized
      symptoms during SC. In the absence of MIS, a BTC <= 20 MUg/L did not increase the
      risk for VIT failure. The most important factors associated with a worse outcome
      were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P < 0.001), honeybee
      venom allergy (OR 5.09, 95% CI 3.17-8.15, P < 0.001), systemic allergic reaction
      during VIT (OR 3.07, 95% CI 1.79-5.14, P < 0.001), and a substantial likelihood
      to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT
      (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68
      per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate.
      CONCLUSION: The magnitude of therapeutic success correlates with type of venom,
      duration of therapy, and venom dose. Adult-onset MIS and/or a BTC > 20 MUg/L is a
      significant, albeit not the strongest determinant for VIT failure. According to
      its odds ratio, ACE inhibitor therapy appears to be associated with the highest
      risk for VIT failure.

PMID- 24447115
TI  - Impaired decoding of fear and disgust predicts utilitarian moral judgment in
      alcohol-dependent individuals.
AB  - BACKGROUND: Recent studies of moral reasoning in patients with alcohol use
      disorders have indicated a "utilitarian" bias, whereby patients are more likely
      to endorse emotionally aversive actions in favor of aggregate welfare (e.g.,
      throwing a dying person into the sea to keep a lifeboat of survivors afloat).
      Here, we investigate the underlying psychological and neuropsychological
      processes. METHODS: Alcohol-dependent individuals (n = 31) and healthy comparison
      participants (n = 34) completed a validated moral judgment task, as well as
      measures of impulsivity, mood symptoms (anxiety and depression), and emotional
      face recognition. RESULTS: Alcohol-dependent individuals were more likely to
      endorse utilitarian choices in personal moral dilemmas compared with controls and
      rated these choices as less difficult to make. Hierarchical regression models
      showed that poorer decoding of fear and disgust significantly predicted
      utilitarian biases in personal moral dilemmas, over and above alcohol
      consumption. Impulsivity and mood symptoms did not predict moral decisions.
      CONCLUSIONS: These findings suggest that impaired fear and disgust decoding
      contributes to utilitarian moral decision-making in alcohol-dependent
      individuals.

PMID- 24447116
TI  - "My Baby & Me": effects of an early, comprehensive parenting intervention on at
      risk mothers and their children.
AB  - This study examined the efficacy of a multimodule parenting intervention, "My
      Baby & Me," that began prenatally and continued until children reached 2.5 years
      of age. The intervention targeted specific parenting skills designed to alter
      trajectories of maternal and child development. Of 361 high-risk mothers (193
      adolescents, 168 adults) enrolled across 4 states, half were randomly assigned to
      the high-intensity (HI) home visitation coaching program (55 sessions), and half
      to a low-intensity (LI) condition that included monthly phone calls from a coach,
      printed informational materials, and community resource referrals. Videotaped
      observations of mother-child play were coded at 5 time points for multiple
      maternal and child behaviors and skills. Compared to mothers in the LI group,
      mothers in the HI group showed higher levels of contingent responsiveness, higher
      quality verbal stimulation, and more verbal scaffolding by 30 months, with higher
      levels of warmth and greater decreases in physical intrusiveness and negativity
      when their children were 24 months. By 30 months, children in the HI group showed
      more rapid increases and higher levels of engagement with the environment,
      expressive language skills, and social engagement, as well as more complex toy
      play and fewer problem behaviors than those in the LI group. Gains in maternal
      responsive behaviors mediated the effects of the intervention on child outcomes.
      Results were comparable for adolescent and adult mothers. A strong theoretical
      framework, consistent focus on maternal responsiveness, high dosage, and trusting
      relationships with coaches are thought to explain the positive outcomes.

PMID- 24447117
TI  - The relation between television exposure and executive function among
      preschoolers.
AB  - This study investigated the relations between television exposure during the
      preschool years and the development of executive function (EF). Data were
      gathered from 107 parents of preschoolers who provided information on children's
      television viewing, background television exposure, exposure to specific
      televised content, and the age at which children began watching television.
      Preschoolers' EF was assessed via one-on-one interviews. We found that several
      indicators of television exposure were significantly related to EF. These
      findings suggest that EF may be an important construct for continued research on
      the effects of media on young children.

PMID- 24447118
TI  - Peers increase adolescent risk taking even when the probabilities of negative
      outcomes are known.
AB  - The majority of adolescent risk taking occurs in the presence of peers, and
      recent research suggests that the presence of peers may alter how the potential
      rewards and costs of a decision are valuated or perceived. The current study
      further explores this notion by investigating how peer observation affects
      adolescent risk taking when the information necessary to make an informed
      decision is explicitly provided. We used a novel probabilistic gambling task in
      which participants decided whether to play or pass on a series of offers for
      which the reward and loss outcome probabilities were made explicit. Adolescent
      participants completed the task either alone or under the belief that they were
      being observed by an unknown peer in a neighboring room. Participants who
      believed a peer was observing them chose to gamble more often than participants
      who completed the task alone, and this effect was most evident for decisions with
      a greater probability of loss. These results suggest that the presence of peers
      can increase risk taking among adolescents even when specific information
      regarding the likelihood of positive and negative outcomes is provided. The
      findings expand our understanding of how peers influence adolescent decision
      making and have important implications regarding the value of educational
      programs aimed at reducing risky behaviors during adolescence.

PMID- 24447120
TI  - Methylation and miRNA effects of resveratrol on mammary tumors vs. normal tissue.
AB  - We reported that resveratrol decreased DNA methyltransferase (DNMT) 1 and 3b
      expression in vitro and demethylates tumor suppressor RASSF-1a in women at
      increased breast cancer risk. We investigated the effects of resveratrol on DNMT
      and miRNA expression in normal and tumor mammary tissue in a rodent model of
      estrogen dependent mammary carcinoma. Eighty-nine female ACI rats received
      estradiol plus: low dose (lo) resveratrol, high dose (hi) resveratrol, 5-aza-2
      deoxycytidine (Aza), a known inhibitor of DNMTs, or control (no additional
      treatment). After 21 wk of treatment, animals were sacrificed and mammary glands
      harvested. Matched tumor/normal tissues were available from 36 rats. DMNT3b (but
      not DNMT1) differed in tumor vs. normal tissue after lo (P = .04) and hi (P =
      .007) resveratrol and Aza treatment. With hi resveratrol, DNMT3b decreased in
      tumor but increased normal tissue. Hi resveratrol increased miR21, -129, -204,
      and -489 >twofold in tumor and decreased the same miRs in normal tissue 10-50%
      compared to control. There was an inverse association between DNMT3b and miR129, 
      204, and -489 in normal and/or tumor tissue. Treatment with resveratrol
      differentially influences tumor vs. normal tissue DNMT3b and miRNA expression.
      This mechanism of action of resveratrol to influence mammary carcinogenesis
      warrants further investigation. 

PMID- 24447123
TI  - Highly sensitive biofunctionalized mesoporous electrospun TiO(2) nanofiber based
      interface for biosensing.
AB  - The surface modified and aligned mesoporous anatase titania nanofiber mats (TiO2
      NF) have been fabricated by electrospinning for esterified cholesterol detection
      by electrochemical technique. The electrospinning and porosity of mesoporous TiO2
      NF were controlled by use of polyvinylpyrrolidone (PVP) as a sacrificial carrier
      polymer in the titanium isopropoxide precursor. The mesoporous TiO2-NF of
      diameters ranging from 30 to 60 nm were obtained by calcination at 470  degrees C
      and partially aligned on a rotating drum collector. The functional groups such as
      -COOH, -CHO etc. were introduced on TiO2-NF surface via oxygen plasma treatment
      making the surface hydrophilic. Cholesterol esterase (ChEt) and cholesterol
      oxidase (ChOx) were covalently immobilized on the plasma treated surface of NF
      (cTiO2-NF) via N-ethyl-N0-(3-dimethylaminopropyl carbodiimide) and N
      hydroxysuccinimide (EDC-NHS) chemistry. The high mesoporosity (~61%) of the
      fibrous film allowed enhanced loading of the enzyme molecules in the TiO2-NF mat.
      The ChEt-ChOx/cTiO2-NF-based bioelectrode was used to detect esterified
      cholesterol using electrochemical technique. The high aspect ratio, surface area
      of aligned TiO2-NF showed excellent voltammetric and catalytic response resulting
      in improved detection limit (0.49 mM). The results of response studies of this
      biosensor show excellent sensitivity (181.6 MUA/mg dL(-1)/cm(2)) and rapid
      detection (20 s). This proposed strategy of biomolecule detection is thus a
      promising platform for the development of miniaturized device for biosensing
      applications. 

PMID- 24447126
TI  - Contralateral auricular composite graft for ear reconstruction.

PMID- 24447124
TI  - Antiseizure drugs differentially modulate theta-burst induced long-term
      potentiation in C57BL/6 mice.
AB  - OBJECTIVE: Cognitive comorbidities are increasingly recognized as an equal (or
      even more disabling) aspect of epilepsy. In addition, the actions of some
      antiseizure drugs (ASDs) can impact learning and memory. Accordingly, the
      National Institute of Neurological Disorders and Stroke (NINDS) epilepsy research
      benchmarks call for the implementation of standardized protocols for screening
      ASDs for their amelioration or exacerbation of cognitive comorbidities. Long-term
      potentiation (LTP) is a widely used model for investigating synaptic plasticity
      and its relationship to learning and memory. Although the effects of some ASDs on
      LTP have been examined, none of these studies employed physiologically relevant
      induction stimuli such as theta-burst stimulation (TBS). To systematically
      evaluate the effects of multiple ASDs in the same preparation using
      physiologically relevant stimulation protocols, we examined the effects of a
      broad panel of existing ASDs on TBS-induced LTP in area CA1 of in vitro brain
      slices, prepared in either normal or sucrose-based artificial cerebrospinal fluid
      (ACSF), from C57BL/6 mice. METHODS: Coronal brain slices containing the dorsal
      hippocampus were made using either standard or sucrose-based ACSF. Recordings
      were obtained from four slices at a time using the Scientifica Slicemaster high
      throughput recording system. Slices exposed to ASDs were paired with slices from
      the opposite hemisphere that served as controls. Field excitatory postsynaptic
      potentials (fEPSPs) were recorded, and all ASDs were applied to slices by bath
      perfusion for 20 min prior to the induction stimulus. LTP was induced by TBS or
      by high-frequency stimulation (HFS). The following ASDs were examined: 100 MUM
      phenobarbital (PB), 80 MUM phenytoin (PHT), 50 MUM carbamazepine (CBZ), 600 MUM
      valproate (VPA), 60 MUM topiramate (TPM), 60 MUM lamotrigine (LTG), 100 MUM
      levetiracetam (LEV), 10 MUM ezogabine (EZG), and 30 MUM tiagabine (TGB). RESULTS:
      Among voltage-gated sodium channel inhibitors, CBZ significantly attenuated TBS
      induced LTP, PHT attenuated both TBS-induced LTP and post-tetanic potentiation
      (PTP), and LTG failed to affect LTP but did attenuate PTP. ASDs that modulate
      gamma-aminobutyric acid (GABA)ergic synaptic transmission, such as PB and TGB,
      significantly attenuated LTP in brain slices prepared in sucrose-based ACSF but
      not standard ACSF. Third generation ASDs, such as LEV and TPM, did not affect LTP
      in ACSF- or sucrose-prepared brain slices. Although EZG failed to affect LTP, it
      did significantly attenuate PTP under both slicing conditions. VPA failed to
      affect LTP in area CA1, both in C57BL/6 mice and Sprague-Dawley rats, using TBS
      or HFS. However, VPA did attenuate TBS-induced LTP in the dentate gyrus (DG).
      SIGNIFICANCE: The results of experiments describe herein provide a comprehensive
      summary of the effects of many commonly used ASDs on short- and long-term
      synaptic plasticity while, for the first time, using physiologically relevant LTP
      induction protocols and slice preparations from mice. Furthermore, methodologic
      variables, such as brain slice preparation protocols, were explored. These
      results provide comparative knowledge of ASD effects on synaptic plasticity in
      the mouse hippocampus and may ultimately contribute to an understanding of the
      differences in the cognitive side effect profiles of ASDs and the prediction of
      cognitive dysfunction associated with novel investigational ASDs.

PMID- 24447127
TI  - "Nok": a phytosterol-based amphiphile enabling transition-metal-catalyzed
      couplings in water at room temperature.
AB  - The third-generation designer amphiphile/surfactant, "Nok" (i.e., SPGS-550-M;
      beta-sitosterol methoxypolyethyleneglycol succinate), soon to be commercially
      available from Aldrich, can be prepared in two steps using an abundant plant
      feedstock and beta-sitosterol, together with succinic anhydride and PEG-550-M.
      Upon dissolution in water, it forms nanomicelles that serve as nanoreactors,
      which can be characterized by both cryo-TEM and dynamic light scattering
      analyses. Several transition-metal-catalyzed reactions have been run under
      micellar conditions to evaluate this surfactant relative to results obtained in
      nanoparticles composed of TPGS-750-M (i.e., a second-generation surfactant). It
      is shown that Nok usually affords yields that are, in general, as good or better
      than those typically obtained with TPGS-750-M, and yet is far less costly. 

PMID- 24447128
TI  - Evaluation of the non-functional tooth contact in patients with temporomandibular
      disorders by using newly developed electronic system.
AB  - The aims of this study were to introduce a novel electronic system for reliable
      evaluation of the non-functional tooth contact in patients with temporomandibular
      disorders (TMDs) and investigate the possible associations between the non
      functional tooth contact and some characteristics of the patients with TMD. We
      designed and installed a software program to send emails regarding the non
      functional tooth contact to the subjects' preregistered cellular phones at
      intervals of 20 +/- 9 min daily for 10 consecutive days. Twelve patients with TMD
      and 12 gender- and age-matched healthy subjects responded via emails to one of 3
      choices: no tooth contact, tooth contact during oral functions or tooth contact
      not associated with oral functions. The influence of subjective stress, anxiety,
      depression, personality and daily activities on tooth contact was then assessed.
      The frequency of the non-functional tooth contact was significantly higher in the
      patients with TMD than in the healthy subjects (35.0% vs. 9.6%, P < 0.001), while
      no significant group difference was found for the frequency of functional tooth
      contact, the stress, anxiety, depression and personality. 

PMID- 24447129
TI  - Entropy-driven pattern formation of hybrid vesicular assemblies made from
      molecular and nanoparticle amphiphiles.
AB  - Although an analogy has been drawn between them, organic molecular amphiphiles
      (MAMs) and inorganic nanoparticle (NP) amphiphiles (NPAMs) are significantly
      different in dimension, geometry, and composition as well as their assembly
      behavior. Their concurrent assembly can synergetically combine the inherent
      properties of both building blocks, thus leading to new hybrid materials with
      increasing complexity and functionality. Here we present a new strategy to
      fabricate hybrid vesicles with well-defined shape, morphology, and surface
      pattern by coassembling MAMs of block copolymers (BCPs) and NPAMs comprising
      inorganic NPs tethered with amphiphilic BCPs. The assembly of binary mixtures
      generated unique hybrid Janus-like vesicles with different shapes, patchy
      vesicles, and heterogeneous vesicles. Our experimental and computational studies
      indicate that the different nanostructures arise from the delicate interplay
      between the dimension mismatch of the two types of amphiphiles, the entanglement
      of polymer chains, and the mobility of NPAMs. In addition, the entropic
      attraction between NPAMs plays a dominant role in controlling the lateral phase
      separation of the two types of amphiphiles in the membranes. The ability to
      utilize multiple distinct amphiphiles to construct discrete assemblies represents
      a promising step in the self-assembly of structurally complex functional
      materials. 

PMID- 24447130
TI  - A novel drug delivery gel of terbinafine hydrochloride with high penetration for
      external use.
AB  - CONTEXT: Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor
      permeability of its external preparation leads to poor curative effect.
      Transfersomes, also known as flexible liposome, could improve transmission of
      drug for local external use. Terbinafine hydrochloride-loaded liposome is
      expected to become a breakthrough on the treatment of onychomycosis. OBJECTIVE:
      This study is aimed to prepare high skin penetration terbinafine hydrochloride
      transfersomes with high encapsulation efficiency, appropriate drug loading and
      good stability. MATERIALS AND METHODS: Taking entrapment efficiency as the main
      indicator, the formulations and the processes of preparation were investigated.
      Transfersomes with different surfactants were prepared in the optimization
      processes, and the formulations were optimized through the transdermal test in
      vitro. As a result, a gel contained transfersomes was obtained with a brief
      evaluation. Its pharmacokinetic properties of going through the skin were studied
      by using the micro dialysis technology and liquid chromatography-mass
      spectrometry to assay the penetration behavior of terbinafine. RESULTS: Mean
      particle size of the terbinafine hydrochloride transfersomes was 69.6 +/- 1.23
      nm, and the entrapment efficiency was 95.4% +/- 0.51. The content of the gel was
      4.45 +/- 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h
      was 88.52 +/- 4.06 ug cm-2 and the intracutaneous drug detention was 94.38 +/-
      5.26 ug cm-2. The results of pharmacokinetic studies showed the Cmax and area
      under the curve (AUC) were apparently higher than the commercial cream.
      DISCUSSION AND CONCLUSION: The terbinafine hydrochloride transfersomes was highly
      absorbed by the skin. The absorption rate was significantly higher than that of
      the commercial cream either in the transdermal test in vitro or in the
      pharmacokinetic studies in vivo.

PMID- 24447131
TI  - A systematic review of sexual dysfunction measures for gay men: how do current
      measures measure up?
AB  - The measurement of subjective components of sexual functioning is of increasing
      importance in clinical research and practice. Differences have been reported in
      prevalence rates and experiences of sexual difficulties between heterosexual and
      gay men. The aim of this article is to identify reliable and valid measures of
      sexual dysfunction suitable for use with gay men. Seven measures were reviewed;
      details about item development, dimensionality, reliability, and validity are
      provided. Heteronormative and heterosexist wording were evident throughout.
      Several areas of concern emerged in relation to psychometric properties (e.g.,
      questionable validity). No psychometrically robust sexual function measure was
      identified for use with gay populations. 

PMID- 24447133
TI  - Coronary artery bypass grafting versus drug-eluting stents in patients with end
      stage renal disease.
AB  - BACKGROUND: The optimal treatment for multivessel coronary artery disease in
      patients with end-stage renal disease (ESRD) is unresolved. AIM OF STUDY: Compare
      clinical adverse events after percutaneous intervention with drug-eluting stents
      (DESs) and coronary artery bypass grafting (CABG) in patients with ESRD. METHODS:
      MEDLINE, Web of Science, and Scopus were searched for appropriate studies
      published in the English language (between January 2000 and August 2013). The
      pooled odds ratio (OR) was estimated by the Peto method with a random effect
      model. Data are presented with 95% confidence interval; p<0.05 is significant.
      RESULTS: Five observational studies (12,035 DES patients; 6317 CABG) with a
      follow-up period of 27.4 +/- 6.3 months were included. Early mortality (CABG 8%
      and DES 2.6%) was less in the DES cohort (OR 0.29 [0.14-0.59]; p=0.0006;
      I(2)=18%). Repeat intervention (DES 29% and CABG 12%) was more likely in the DES
      cohort (OR 3.72 [2.24-6.18]: p<0.0001). Late mortality (27.4 +/- 7.3 months) was
      comparable in both cohorts (OR 0.72 [0.40-1.29]; p=0.27). While DES cohort (32%)
      patients suffered a slightly higher incidence of major adverse cardiac and
      cerebrovascular events (MACCE) as compared to CABG (25%), this was not
      significant (1.35 [0.72-2.53]; p=0.35; I(2)=30%). CONCLUSION: Data regarding this
      topic are limited to small retrospective studies. Early mortality is lower with
      DESs compared with coronary artery bypass in patients with ESRD. Rate of
      reintervention is significantly higher in the DES cohort. At a mean pooled follow
      up of two years, both mortality and MACCE are comparable in both cohorts.

PMID- 24447134
TI  - Seamlessly rewriting the lab cloning manual.

PMID- 24447135
TI  - Quantitative analysis of colony morphology in yeast.
AB  - Microorganisms often form multicellular structures such as biofilms and
      structured colonies that can influence the organism's virulence, drug resistance,
      and adherence to medical devices. Phenotypic classification of these structures
      has traditionally relied on qualitative scoring systems that limit detailed
      phenotypic comparisons between strains. Automated imaging and quantitative
      analysis have the potential to improve the speed and accuracy of experiments
      designed to study the genetic and molecular networks underlying different
      morphological traits. For this reason, we have developed a platform that uses
      automated image analysis and pattern recognition to quantify phenotypic
      signatures of yeast colonies. Our strategy enables quantitative analysis of
      individual colonies, measured at a single time point or over a series of time
      lapse images, as well as the classification of distinct colony shapes based on
      image-derived features. Phenotypic changes in colony morphology can be expressed
      as changes in feature space trajectories over time, thereby enabling the
      visualization and quantitative analysis of morphological development. To
      facilitate data exploration, results are plotted dynamically through an
      interactive Yeast Image Analysis web application (YIMAA; http://yimaa.cs.tut.fi)
      that integrates the raw and processed images across all time points, allowing
      exploration of the image-based features and principal components associated with
      morphological development. 

PMID- 24447136
TI  - AG-NGS: a powerful and user-friendly computing application for the semi-automated
      preparation of next-generation sequencing libraries using open liquid handling
      platforms.
AB  - Next-generation sequencing (NGS) is becoming one of the most widely used
      technologies in the field of genomics. Library preparation is one of the most
      critical, hands-on, and time-consuming steps in the NGS workflow. Each library
      must be prepared in an independent well, increasing the number of hours required
      for a sequencing run and the risk of human-introduced error. Automation of
      library preparation is the best option to avoid these problems. With this in
      mind, we have developed automatic genomics NGS (AG-NGS), a computing application
      that allows an open liquid handling platform to be transformed into a library
      preparation station without losing the potential of an open platform.
      Implementation of AG-NGS does not require programming experience, and the
      application has also been designed to minimize implementation costs. Automated
      library preparation with AG-NGS generated high-quality libraries from different
      samples, demonstrating its efficiency, and all quality control parameters fell
      within the range of optimal values. 

PMID- 24447137
TI  - A technique to increase protein yield in a rabbit reticulocyte lysate translation
      system.
AB  - Rabbit reticulocyte lysate (RRL) is a mammalian cell-free system for protein
      production. However, one of the limitations of this system is its low protein
      yield. Inclusion of recombinant virus proteins and specific viral structures on
      target mRNA could enhance protein production in RRL. Here we show that
      simultaneous addition of influenza A virus NS1 protein and inclusion of the
      encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) in the
      target mRNA facilitate translation initiation and increase protein yield over 10
      fold, improving the translation capacity of RRL. 

PMID- 24447138
TI  - Robust and artifact-free mounting of tissue samples for atomic force microscopy.
AB  - Immobilization of tissue-samples for atomic for microscopy (AFM) is typically
      done using either semi-dry tissue or by gluing the tissue sample down, both of
      which can introduce artifacts. Here, we describe the design of a Soft- Clamping
      Immobilizing Retainer of Tissue (SCIRT) for consistent and nondestructive
      immobilization of tissues for AFM analysis. We compare the performance of our
      SCIRT method with glue-immobilization for two difficult to handle tissue types:
      human trabecular meshwork (HTM) and rabbit cornea (RC). Our results demonstrate
      that the SCIRT method has several advantages, including: (i) allowing for small
      sample sizes, (ii) enabling continuous hydration, (iii) eliminating contact with
      glue or associated solvents, (iv) permitting sample recovery following
      measurement, and (v) ease of use. In conclusion, the SCIRT method is a simple and
      effective means of immobilizing soft, hydrated tissue samples consistently and
      without artifacts. 

PMID- 24447139
TI  - Educational intervention to reduce inappropriate transthoracic echocardiograms:
      the need for sustained intervention.
AB  - BACKGROUND: We previously demonstrated that an Appropriate Use Criteria (AUC)
      based educational intervention reduced inappropriate transthoracic
      echocardiograms (TTE) on an inpatient medical service. Whether improved TTE
      ordering is sustained after discontinuation of the intervention is unknown.
      METHODS: We conducted a prospective, time series analysis of an educational
      intervention designed to reduce inappropriate TTE. Ordering patterns during the
      intervention were compared with a preintervention control period and a
      postintervention period. The goal of the present analysis was to determine the
      TTE ordering patterns after discontinuation of the educational intervention. The
      primary outcome was the proportion of inappropriate TTEs. RESULTS: Using the 2011
      AUC 99.2% of all TTEs were classifiable. Compared to the control, there was a 26%
      reduction in the number of TTEs ordered per day during the intervention (3.9 vs.
      2.9 TTEs, P < 0.001), but no significant difference between the intervention and
      postintervention periods (2.9 vs. 3.1, P = 0.23). The intervention produced a
      decrease in the inappropriate TTE rate and an increase in the appropriate TTE
      rate. Compared to the intervention, in the postintervention period the rate of
      inappropriate TTEs increased (5% vs. 11%, P = 0.01) and appropriate TTEs
      decreased (93% vs. 86%, P = 0.008). The postintervention rate of inappropriate
      TTEs was similar to the preintervention control period (11% vs. 13%, P = 0.23).
      CONCLUSIONS: Following completion of an AUC-based educational intervention the
      proportion of inappropriate TTEs increased to the preintervention level. The long
      term success of an intervention designed to improve appropriate utilization of
      TTE requires a sustained effort of education and feedback.

PMID- 24447140
TI  - Inhibition of interleukin-1beta production by extracellular acidification through
      the TDAG8/cAMP pathway in mouse microglia.
AB  - Interleukin-1beta (IL-1beta) is released from activated microglia and involved in
      the neurodegeneration of acute and chronic brain disorders, such as stroke and
      Alzheimer's disease, in which extracellular acidification has been shown to
      occur. Here, we examined the extracellular acidic pH regulation of IL-1beta
      production, especially focusing on TDAG8, a major proton-sensing G-protein
      coupled receptor, in mouse microglia. Extracellular acidification inhibited
      lipopolysaccharide -induced IL-1beta production, which was associated with the
      inhibition of IL-1beta cytoplasmic precursor and mRNA expression. The IL-1beta
      mRNA and protein responses were significantly, though not completely, attenuated
      in microglia derived from TDAG8-deficient mice compared with those from wild-type
      mice. The acidic pH also stimulated cellular cAMP accumulation, which was
      completely inhibited by TDAG8 deficiency. Forskolin and a cAMP derivative, which
      specifically stimulates protein kinase A (PKA), mimicked the proton actions, and
      PKA inhibitors reversed the acidic pH-induced IL-1beta mRNA expression. The
      acidic pH-induced inhibitory IL-1beta responses were accompanied by the
      inhibition of extracellular signal-related kinase and c-Jun N-terminal kinase
      activities. The inhibitory enzyme activities in response to acidic pH were
      reversed by the PKA inhibitor and TDAG8 deficiency. We conclude that
      extracellular acidic pH inhibits lipopolysaccharide-induced IL-1beta production,
      at least partly, through the TDAG8/cAMP/PKA pathway, by inhibiting extracellular
      signal-related kinase and c-Jun N-terminal kinase activities, in mouse microglia.

PMID- 24447145
TI  - Active silicon integrated nanophotonics: ferroelectric BaTiO3 devices.
AB  - The integration of complex oxides on silicon presents opportunities to extend and
      enhance silicon technology with novel electronic, magnetic, and photonic
      properties. Among these materials, barium titanate (BaTiO3) is a particularly
      strong ferroelectric perovskite oxide with attractive dielectric and electro
      optic properties. Here we demonstrate nanophotonic circuits incorporating
      ferroelectric BaTiO3 thin films on the ubiquitous silicon-on-insulator (SOI)
      platform. We grow epitaxial, single-crystalline BaTiO3 directly on SOI and
      engineer integrated waveguide structures that simultaneously confine light and an
      RF electric field in the BaTiO3 layer. Using on-chip photonic interferometers, we
      extract a large effective Pockels coefficient of 213 +/- 49 pm/V, a value more
      than six times larger than found in commercial optical modulators based on
      lithium niobate. The monolithically integrated BaTiO3 optical modulators show
      modulation bandwidth in the gigahertz regime, which is promising for broadband
      applications. 

PMID- 24447144
TI  - Angiotensin-converting enzyme inhibitors do not impair the safety of Hymenoptera
      venom immunotherapy build-up phase.
AB  - BACKGROUND: There is an ongoing debate on whether angiotensin-converting enzyme
      inhibitors (ACEI) should be substituted prior to initiation of venom
      immunotherapy (VIT) for safety reasons. OBJECTIVE: We aimed to assess the
      influence of ACEI medication on the incidence of systemic reactions (SR) during
      the build-up phase of VIT in a large and homogeneous cohort of patients. METHODS:
      The frequency of SR during 775 consecutive cycles of VIT initiation was analyzed
      in relation to cardiovascular medication, age, sex, venom, reactivity in
      diagnostic tests, severity of preceding sting-induced anaphylaxis, comorbidities,
      latency before the initiation of VIT, and treatment protocols. ACEI were
      routinely maintained throughout VIT, beta-blockers replaced if appropriate.
      RESULTS: During VIT-initiation, 190 (24.5%) patients were on some kind of
      cardiovascular treatment, 90 (11.6%) on ACEI, 23 (3.0%) on beta-blockers. VIT
      related SR rates were 11.7% (any documented reactions including subjective
      symptoms) and 3.0% (reactions fulfilling objective diagnostic criteria of
      anaphylaxis). Medication with ACEI (P = 0.097) or beta-blockers (P = 1.0) was not
      significantly related to the incidence of SR. A reduced rate of SR in patients
      taking cardiovascular drugs was not statistically significant in the final
      multivariate regression model. A prolonged latency before the initiation of VIT
      (P = 0.018, odds ratio = 1.010), and use of 5-day compared to 3-day rush
      protocols (P = 0.008, odds ratio = 3.522) increased the frequency of SR.
      CONCLUSIONS AND CLINICAL RELEVANCE: Study data do not provide evidence of an ACEI
      mediated increase of VIT-related SR, supporting the continued use of these
      valuable and hard-to-replace substances throughout VIT.

PMID- 24447148
TI  - Methylseleninic acid suppresses pancreatic cancer growth involving multiple
      pathways.
AB  - As a potential novel agent for treating pancreatic cancer, methylseleninic acid
      (MSeA) was evaluated in cell culture and xenograft models. Results showed that
      MSeA induced G1 cell cycle arrest and apoptosis in a majority of human and mouse
      pancreatic cancer cell lines, but G2 arrest in human PANC-1 and PANC-28 cell
      lines. In contrast to our previous finding in human prostate cancer LNCaP cells
      having a lack of P53 activation by MSeA, induction of G2 arrest in PANC-1 cells
      was accompanied by increased mutant P53 Ser15 phosphorylation, upregulation of
      P53-targets P21Cip1 and GADD45 and G2 checkpoint kinase (Chk2) activation,
      suggestive of DNA damage responses. A rapid inhibition of AKT phosphorylation was
      followed by reduced mTOR signaling and increased autophagy in PANC-1 cells
      attenuating caspase-mediated apoptosis execution. Furthermore, daily oral
      treatment with MSeA (3 mg Se/kg body weight) significantly suppressed growth of
      subcutaneously inoculated PANC-1 xenograft in SCID mice. Immunohistochemical
      analyses detected increased p-Ser15 P53, P21Cip1, pS139-H2AX (DNA damage
      responses), and caspase-3 cleavage and decreased pSer473AKT and Ki67
      proliferative index and reduced intratumor vascular density in MSeA-treated
      xenograft. These results provide impetus for further research of MSeA in the
      therapy and/or chemoprevention of pancreatic cancer.

PMID- 24447149
TI  - Fabrication of monodisperse porous zirconia microspheres and their
      phosphorylation for Friedel-Crafts alkylation of indoles.
AB  - Monodisperse porous zirconia (ZrO2) microspheres with nanocrystallized framework
      were fabricated by impregnation of porous polymer microspheres as a novel hard
      template with zirconia precursors followed by calcination to remove the template.
      Porous phosphorylated zirconia (PhZr) microspheres were prepared by further
      treating porous zirconia microspheres with phosphoric acid. The morphology,
      structure, and properties of these microspheres were studied by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), N2
      adsorption/desorption measurement, FT-IR, and X-ray powder diffraction. The as
      prepared zirconia and phosphorylated zirconia microspheres showed uniform
      particle size and well-defined morphology. The phosphorylated zirconia
      microspheres served as highly active solid acid catalysts for Friedel-Crafts
      alkylation of indoles with chalcones and could be reused for 22 cycles with
      negligible loss of activity. In situ pyridine-adsorbed FT-IR analysis of the best
      performing PhZr microspheres suggested the presence of both Lewis and Bronsted
      acid sites, and the total acidity as measured by temperature-programmed
      desorption of ammonia (NH3-TPD) was 328 MUmol.g(-1). 

PMID- 24447150
TI  - Shared decision-making, stigma, and child mental health functioning among
      families referred for primary care-located mental health services.
AB  - There is growing emphasis on shared decision making (SDM) to promote family
      participation in care and improve the quality of child mental health care. Yet,
      little is known about the relationship of SDM with parental perceptions of child
      mental health treatment or child mental health functioning. The objectives of
      this preliminary study were to examine (a) the frequency of perceived SDM with
      providers among minority parents of children referred to colocated mental health
      care in a primary care clinic, (b) associations between parent-reported SDM and
      mental health treatment stigma and child mental health impairment, and (c)
      differences in SDM among parents of children with various levels of mental health
      problem severity. Participants were 36 Latino and African American parents of
      children (ages 2-7 years) who were referred to colocated mental health care for
      externalizing mental health problems (disruptive, hyperactive, and aggressive
      behaviors). Parents completed questions assessing their perceptions of SDM with
      providers, child mental health treatment stigma, child mental health severity,
      and level of child mental health impairment. Descriptive statistics demonstrated
      the majority of the sample reported frequent SDM with providers. Correlation
      coefficients indicated higher SDM was associated with lower stigma regarding
      mental health treatment and lower parent-perceived child mental health
      impairment. Analysis of variance showed no significant difference in SDM among
      parents of children with different parent-reported levels of child mental health
      severity. Future research should examine the potential of SDM for addressing
      child mental health treatment stigma and impairment among minority families.

PMID- 24447151
TI  - Reliability and normative data for the Behavioral Health Measure (BHM) in primary
      care behavioral health settings.
AB  - The Behavioral Health Measure (BHM) is a brief self-report measure of general
      psychological distress and functioning developed for the tracking of mental
      health outcomes in outpatient psychotherapy settings (Kopta & Lowry, 2002).
      Although the BHM is used in integrated primary care behavioral health clinics,
      the scale's psychometric properties have not been evaluated in these settings.
      The current study investigated the BHM's psychometric properties, including its
      factor structure and reliability, and presents normative data from 3 large
      integrated primary care clinics. Mean scores for each of the BHM's 4 scales were
      significantly lower (i.e., more distress) for women than men, with scores being
      stable across the 3 primary care samples. Confirmatory factor analysis
      demonstrated adequate fit for the 3-factor and 1-factor models, with fit
      improving when 3 items were omitted. Internal consistency estimates for the BHM's
      4 scales ranged from adequate to very good (alpha range: .72-.93). The 4 scales
      were highly intercorrelated, suggesting they measure similar constructs. Results
      suggest a revised, 17-item version of the BHM has adequate structure and
      reliability estimates, and is appropriate for use in primary care settings.

PMID- 24447152
TI  - Older couples with and without cardiovascular disease: testing associations
      between and among affective communication, marital satisfaction, physical and
      mental health.
AB  - The American Heart Association (Go et al., 2013) estimated that about 2,150
      Americans die each day from cardiovascular disease (CVD). For those 65 years of
      age or older, the total cost of heart related services in 2009 was $121.2 billion
      (Go et al., 2013). Many people live with the chronic conditions of cardiovascular
      disease (Petersen et al., 2005). Researchers have identified the genetic,
      medical, and lifestyle habits of those with CVD, yet there is a dearth of
      literature focusing on the relational/social aspects of cardiovascular disease
      and how such factors are associated with the risk, presentation, and maintenance
      of cardiovascular illness. Considering that men have a higher lifetime risk for
      developing CVD than women (51.7% to 39.2%; Roger et al., 2012), the purpose of
      this study was to compare various aspects of the couple relationship among and
      between couples with a husband who reports CVD and couples in which neither
      report CVD.

PMID- 24447154
TI  - Including students with disabilities in urban public schools: community
      psychology theory and research.

PMID- 24447155
TI  - Two ecological models of academic achievement among diverse students with and
      without disabilities in transition.
AB  - School experiences can have positive effects on student academic achievement, yet
      less is known about intermediary processes that contribute to these positive
      effects. We examined pathways between school experiences and academic achievement
      among 117 low-income urban students of color, many with disabilities, who
      transitioned to other schools following a school closure. Using structural
      equation modeling, we tested two ecological models that examined the
      relationships among self-reported school experiences, school support, academic
      self-efficacy, and school-reported academic achievement. The model in which the
      relationship between school experiences and academic achievement is mediated by
      both school support and academic self-efficacy, and that takes previous academic
      achievement into account, was an excellent fit with the data. The roles of
      contextual and individual factors as they relate to academic achievement, and the
      implications of these findings, are discussed. 

PMID- 24447156
TI  - Student-teacher relationships matter for school inclusion: school belonging,
      disability, and school transitions.
AB  - For students with disabilities, the process of school inclusion often begins with
      a move from segregated settings into general education classrooms. School
      transitions can be stressful as students adjust to a new environment. This study
      examines the adjustment of 133 students with and without disabilities who moved
      from a school that served primarily students with disabilities into 23 public
      schools in a large urban school district in the Midwest. These students and 111
      of their teachers and other school staff rated the degree that students felt they
      belonged in their new schools and the quality of their social interactions.
      Results show that students who experienced more positive and fewer negative
      social interactions with school staff had higher school belonging. Teachers
      accurately noted whether students felt they belonged in their new settings, but
      were not consistently able to identify student perceptions of negative social
      interactions with staff. Implications for inclusion and improving our educational
      system are explored. 

PMID- 24447157
TI  - Transportation and socioemotional well-being of urban students with and without
      disabilities.
AB  - This study explored the extent to which transportation difficulties were
      associated with social, psychological, and academic experiences of urban, at-risk
      students who recently experienced a school transition. Participants included 165
      predominantly African American and Latino/a high school youth with and without
      disabilities, a critical population for community psychology to address given
      their likelihood of multiple marginalizations. Results suggested transportation
      problems within school predicted more school stressors and aggressive behavior.
      Transportation problems to and from school predicted fewer school resources, less
      school belonging, and more school stressors, anxiety, and depression. Greater
      time to get to school predicted fewer school resources, less school belonging,
      and more depressive symptoms. This study demonstrates the importance of including
      transportation in how the school day is conceptualized, and offers several
      implications for how transportation services can be best addressed. 

PMID- 24447158
TI  - Transportation challenges for urban students with disabilities: parent
      perspectives.
AB  - This qualitative study explored parent perspectives of the transportation
      difficulties students with disabilities experienced getting to and around school.
      Participants were parents of predominantly African American and Latino/a high
      school youth with disabilities from low income neighborhoods. Content analysis of
      14 meetings with 5 to 12 parents sponsored by the school district revealed five
      primary themes concerning transportation: the role of aides, exclusion from
      school programming, scheduling problems, equipment problems, and physical safety
      issues. Findings are discussed in regard to students' social and emotional
      experiences at school. Implications for school policy include improving the
      integration of transportation within inclusion best practice models.
      Incorporating parent perspectives can help school administrators and staff enrich
      the quality of inclusive, socially just education for students with disabilities.

PMID- 24447159
TI  - School problems and solutions for students with disabilities: a qualitative
      examination.
AB  - The inclusion of students with disabilities is a process that requires
      collaboration among multiple individuals, with teachers, aides, parents,
      students, and school systems playing important roles in resolving student
      problems. In the current study, we examined data from 75 teachers concerning 126
      students about problems that students with disabilities had following a
      transition from a school primarily serving students with disabilities to more
      inclusive schools. Reported problems were reviewed and five major themes emerged:
      academic, behavioral, mobility/accessibility, social, and transportation issues.
      Teachers typically resolved academic problems by working directly with the
      student or collaborating with school staff. Social problems were resolved through
      student and teacher initiatives. Behavioral, transportation, and
      mobility/accessibility problems were resolved through collaboration among many
      key school figures and family members. Implications for theory, research, and
      inclusive school practices related to academic curricula, resources, services,
      and architectural accommodations for students with disabilities are discussed. 

PMID- 24447160
TI  - Collaborative teaching: school implementation and connections with outcomes among
      students with disabilities.
AB  - Collaborative teaching is a widely used method of including and supporting
      students with disabilities to provide all students equal access to education.
      Yet, there is a dearth of research on its implementation and outcomes, and the
      few existing studies are limited to academic and testing outcomes. This study
      assesses the degree to which schools are implementing co-teaching practices and
      the relation between co-teaching and student psychosocial outcomes using a mixed
      method design. Data from 12 schools, which included 16 school leaders and staff,
      13 teachers, and 56 students with disabilities, were examined. Schools achieved 0
      75% of the co-teaching best-practices criteria, with the majority achieving 25%
      50% of the criteria. Higher levels of teacher-reported co-teaching were related
      to higher levels of student-reported school belonging, school satisfaction, and
      self-efficacy for new experiences. The benefits and challenges of co-teaching, as
      well as implications for intervention and research are addressed. 

PMID- 24447161
TI  - Clinician survey of language sampling practices in Australia.
AB  - A national online survey was used to investigate spontaneous language sampling
      and analysis practices by speech-language pathologists working with children and
      adolescents. A total of 257 responses were received from clinicians around
      Australia. Results indicated that spontaneous language samples are collected on a
      routine basis in elicitation contexts deemed appropriate to the clients' age or
      developmental stage. However, language samples were generally short, often not
      recorded, and analysed informally. Consistent with previous research into
      language sampling practices, the main barrier to more detailed language sample
      analysis appears to be the time needed for transcription. Despite rapid
      technological advances in the last two decades, only 12.5% of the respondents
      reported using computer-assisted transcription and analysis procedures.
      Suggestions are made on how to promote change in clinical practice to ensure
      spontaneous language samples are transcribed and analysed in more detail. By
      transcribing the samples, detailed analysis of children's language performance
      can be undertaken, allowing for effective goal-setting and assisting in objective
      progress measuring during and following intervention.

PMID- 24447162
TI  - Acute evaluation of conversational discourse skills in traumatic brain injury.
AB  - This study looked at performance on the conversational discourse checklist of the
      Protocole Montreal d'evaluation de la communication (D-MEC) in 195 adults with
      TBI of all severity hospitalized in a Level 1 Trauma Centre. To explore validity,
      results were compared to findings on tests of memory, mental flexibility,
      confrontation naming, semantic and letter category naming, verbal reasoning, and
      to scores on the Montreal Cognitive Assessment. The relationship to outcome as
      measured with the Disability Rating Scale (DRS), the Extended Glasgow Outcome
      Scale (GOS-E), length of stay, and discharge destinations was also determined.
      Patients with severe TBI performed significantly worse than mild and moderate
      groups (chi(2)(KW2df) = 24.435, p = .0001). The total D-MEC score correlated
      significantly with all cognitive and language measures (p < .05). It also had a
      significant moderate correlation with the DRS total score (r = -.6090, p < .0001)
      and the GOS-E score (r = .539, p < .0001), indicating that better performance on
      conversational discourse was associated with a lower disability rating and better
      global outcome. Finally, the total D-MEC score was significantly different
      between the discharge destination groups (F(3,90) = 20.19, p < .0001). Thus,
      early identification of conversational discourse impairment in acute care post
      TBI was possible with the D-MEC and could allow for early intervention in speech
      language pathology.

PMID- 24447163
TI  - A geographical analysis of speech-language pathology services to support
      multilingual children.
AB  - The speech-language pathology workforce strives to provide equitable, quality
      services to multilingual people. However, the extent to which this is being
      achieved is unknown. Participants in this study were 2849 members of Speech
      Pathology Australia and 4386 children in the Birth cohort of the Longitudinal
      Study of Australian Children (LSAC). Statistical and geospatial analyses were
      undertaken to identify the linguistic diversity and geographical distribution of
      Australian speech-language pathology services and Australian children. One fifth
      of services offered by Speech Pathology Australia members (20.2%) were available
      in a language other than English. Services were most commonly offered in
      Australian Sign Language (Auslan) (4.3%), French (3.1%), Italian (2.2%), Greek
      (1.6%), and Cantonese (1.5%). Among 4-5-year-old children in the nationally
      representative LSAC, 15.3% regularly spoke and/or understood a language other
      than English. The most common languages spoken by the children were Arabic
      (1.5%), Italian (1.2%), Greek (0.9%), Spanish (0.9%), and Vietnamese (0.9%).
      There was a mismatch between the location of and languages in which multilingual
      services were offered, and the location of and languages spoken by children.
      These findings highlight the need for SLPs to be culturally competent in
      providing equitable services to all clients, regardless of the languages they
      speak.

PMID- 24447164
TI  - Comparative pharmacokinetics of a marker compound, baicalin in KOB extract after
      oral administration to normal and allergic-induced rats.
AB  - KOB extracts are a polyherbal medicine had been prescribed for the treatment of
      hyperhydrosis and allergic diseases such as allergic asthma and rhinitis in
      oriental clinics. Therefore, the pharmacokinetic studies of the KOB extract
      administered orally to normal rats and rhinitis-induced rats to understand the
      correlation of the efficacy and plasma concentration of KOB in patients of
      allergic rhinitis in future were performed. The study was conducted according to
      administration for pure baicalin in normal rats, baicalin in KOB extract in
      normal rats and rhinitis-induced rats. Baicalin in rat plasma was analyzed and
      validated by HPLC analysis. The interday precision based on the standard
      deviation of replicates of quality control samples ranged from 3.6% to 7.9% with
      accuracy ranging from 92.9% to 101.2% for baicalin. Based on validated analysis,
      pharmacokinetic study was carried out. Pure baicalin in normal rats and baicalin
      in KOB extract in normal rats showed bimodal curves due to direct absorption and
      glucuronidation. The Tmax, Cmax and AUC of pure baicalin in normal rats or
      baicalin in KOB extract in normal rats were 12 h, 0.68 ug/ml and 9.85 ug h/ml,
      respectively, or 12 h, 0.46 ug/ml and 6.36 ug h/ml, respectively. The analytical
      method showed excellent sensitivity, precision and accuracy, being successfully
      employed in a pharmacokinetic study of polyherbal medicine, KOB extract. Allergic
      induced condition did not affect the pharmacokinetics of KOB extracts, suggesting
      KOB extracts did not require dosage adjustment in subjects with allergic-induced
      diseases.

PMID- 24447165
TI  - Image analysis of food particles can discriminate deficient mastication of mixed
      foodstuffs simulating daily meal.
AB  - Because food texture is regarded as an important factor for smooth deglutition,
      identification of objective parameters that could provide a basis for food
      texture selection for elderly or dysphagic patients is of great importance. We
      aimed to develop an objective evaluation method of mastication using a mixed test
      food comprising foodstuffs, simulating daily dietary life. The particle size
      distribution (>2 mm in diameter) in a bolus was analysed using a digital image
      under dark-field illumination. Ten female participants (mean age +/- s.d., 27.6
      +/- 2.6 years) masticated a mixed test food comprising prescribed amounts of
      rice, sausage, hard omelette, raw cabbage and raw cucumber with 100%, 75%, 50%
      and 25% of the number of their masticatory strokes. A single set of coefficient
      thresholds of 0.10 for the homogeneity index and 1.62 for the particle size index
      showed excellent discrimination of deficient masticatory conditions with high
      sensitivity (0.90) and specificity (0.77). Based on the results of this study,
      normal mastication was discriminated from deficient masticatory conditions using
      a large particle analysis of mixed foodstuffs, thus showing the possibility of
      future application of this method for objective decision-making regarding the
      properties of meals served to dysphagic patients. 

PMID- 24447166
TI  - Incidence and correlates in the development of iatrogenic femoral pseudoaneurysm
      after percutaneous coronary interventions.
AB  - OBJECTIVE: We aimed to identify the correlates in the development of post
      percutaneous coronary intervention (PCI) iatrogenic femoral pseudoaneurysm (IFP).
      BACKGROUND: IFP is one of the more common vascular complications of PCI. METHODS:
      From February 2008 to June 2012, 10,169 consecutive patients who underwent PCI
      were retrospectively studied. Patients who developed postprocedural IFP were
      identified at a single, large tertiary PCI center. RESULTS: One hundred thirty
      nine patients developed IFP (1.38%) and were compared to the cohort that did not.
      Baseline characteristics were comparable, although patients in the IFP group were
      older and had a higher incidence of insulin-requiring diabetes mellitus and
      chronic renal insufficiency (68.4 +/- 12.9 vs. 65.4 +/- 12.3 years, P = 0.004;
      23.9% vs. 14.6%, P = 0.002; and 26.6% vs. 17.3%, P = 0.004, respectively). The
      non-IFP group had more men and a higher use of vascular closure devices,
      respectively (64.7% vs. 49.6%, P < 0.001; and 54.1% vs. 26.5%, P < 0.001). There
      was no significant difference in the use of dual antiplatelet or anticoagulation
      therapies between the 2 cohorts. Univariable correlates for the development of
      IFP were female gender, insulin-requiring diabetes mellitus, chronic renal
      insufficiency, and use of manual compression to achieve hemostasis. On
      multivariable analysis, the successful deployment of vascular closure device for
      hemostasis reduced the occurrence of IFP (odds ratio 0.31, 95% confidence
      interval 0.21-0.46, P < 0.0001). CONCLUSION: The development of IFP following PCI
      is not uncommon and the appropriate use of vascular closure devices to achieve
      hemostasis should be encouraged to minimize this vascular complication.

PMID- 24447167
TI  - Design and synthesis of a FlAsH-type Mg2+ fluorescent probe for specific protein
      labeling.
AB  - Although the magnesium ion (Mg(2+)) is one of the most abundant divalent cations
      in cells and is known to play critical roles in many physiological processes, its
      mobilization and underlying mechanisms are still unknown. Here, we describe a
      novel fluorescent Mg(2+) probe, "KMG-104-AsH", composed of a highly selective
      fluorescent Mg(2+) probe, "KMG-104", and a fluorescence-recoverable probe,
      "FlAsH", bound specifically to a tetracysteine peptide tag (TCtag), which can be
      genetically incorporated into any protein. This probe was developed for molecular
      imaging of local changes in intracellular Mg(2+) concentration. KMG-104-AsH was
      synthesized, and its optical properties were investigated in solution. The
      fluorescence intensity of KMG-104-AsH (at lambda(em/max) = 540 nm) increases by
      more than 10-fold by binding to both the TCtag peptide and Mg(2+), and the probe
      is highly selective for Mg(2+) (K(d/Mg) = 1.7 mM, K(d/Ca) ? 100 mM). Application
      of the probe for imaging of Mg(2+) in HeLa cells showed that this FlAsH-type
      Mg(2+) sensing probe is membrane-permeable and binds specifically to tagged
      proteins, such as TCtag-actin and mKeima-TCtag targeted to the cytoplasm and the
      mitochondrial intermembrane space. KMG-104-AsH bound to TCtag responded to an
      increase in intracellular Mg(2+) concentration caused by the release of Mg(2+)
      from mitochondria induced by FCCP, a protonophore that eliminates the inner
      membrane potential of mitochondria. This probe is expected to be a strong tool
      for elucidating the dynamics and mechanisms of intracellular localization of
      Mg(2+).

PMID- 24447171
TI  - Immunomodulatory effects of licochalcone A on experimental autoimmune
      encephalomyelitis.
AB  - OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) is a murine
      autoimmune disease used to study multiple sclerosis. Herein, we have investigated
      the immunomodulatory effect of licochalcone A (LicoA) on NO, H2 O2 , tumour
      necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma) and IL-17
      production in cultured cells from EAE mice. METHODS: EAE was induced in C57Bl/6
      mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55 ). LicoA was
      isolated from the roots of Glycyrrhiza inflata. Splenocytes were obtained from
      EAE mice and incubated with LicoA (4, 20 and 40 MUm). Peritoneal cells were
      obtained from EAE mice treated with LicoA (15 and 30 mg/kg/day. p.o.). H2 O2 ,
      NO, IFN-gamma, TNF-alpha and IL-17 production was determined in the presence or
      absence of concanavalin (ConA) or MOG35-55 stimulation. KEY FINDINGS: LicoA (40
      MUm) inhibited H2 O2 , NO, IFN-gamma, TNF-alpha and IL-17 production in
      splenocytes spontaneously or after both ConA and MOG35-55 stimulation. LicoA (30
      mg/kg/day) reduced clinical score and severity of EAE mice, and inhibited TNF
      alpha, IFN-gamma and IL-17 production in peritoneal cells. CONCLUSIONS: LicoA
      possesses immunomodulatory effects on H2 O2 , NO, IFN-gamma, TNF-alpha and IL-17
      production in cells from EAE mice. It is suggested that LicoA acts on the
      mechanism of development of EAE by IFN-gamma, IL-17 and TNF-alpha inhibition,
      modulating the immune response on both Th1 and Th17 cells.

PMID- 24447172
TI  - Extensive amplification of the E2F transcription factor binding sites by
      transposons during evolution of Brassica species.
AB  - Transposable elements (TEs) are major players in genome evolution. The effects of
      their movement vary from gene knockouts to more subtle effects such as changes in
      gene expression. It has recently been shown that TEs may contain transcription
      factor binding sites (TFBSs), and it has been proposed that they may rewire new
      genes into existing transcriptional networks. However, little is known about the
      dynamics of this process and its effect on transcription factor binding. Here we
      show that TEs have extensively amplified the number of sequences that match the
      E2F TFBS during Brassica speciation, and, as a result, as many as 85% of the
      sequences that fit the E2F TFBS consensus are within TEs in some Brassica
      species. We show that these sequences found within TEs bind E2Fa in vivo, which
      indicates a direct effect of these TEs on E2F-mediated gene regulation. Our
      results suggest that the TEs located close to genes may directly participate in
      gene promoters, whereas those located far from genes may have an indirect effect
      by diluting the effective amount of E2F protein able to bind to its cognate
      promoters. These results illustrate an extreme case of the effect of TEs in TFBS
      evolution, and suggest a singular way by which they affect host genes by
      modulating essential transcriptional networks. 

PMID- 24447173
TI  - Tannin-rich fraction from pomegranate rind damages membrane of Listeria
      monocytogenes.
AB  - Pomegranate rind has been reported to inhibit several foodborne pathogens, and
      its antimicrobial activity has been attributed mainly to its tannin fraction.
      This study aimed to investigate the antimicrobial activity of the tannin-rich
      fraction from pomegranate rind (TFPR) against Listeria monocytogenes and its
      mechanism of action. The tannin-related components of TFPR were analyzed by high
      performance liquid chromatography and liquid chromatography-mass spectrometry,
      and the minimum inhibitory concentration (MIC) of TFPR was determined using the
      agar dilution method. Extracellular potassium concentration, the release of cell
      constituents, intra- and extracellular ATP concentrations, membrane potential,
      and intracellular pH (pHin) were measured to elucidate a possible antibacterial
      mechanism. Punicalagin (64.2%, g/g) and ellagic acid (3.1%, g/g) were detected in
      TFPR, and the MICs of TFPR were determined to be 1.25-5.0 mg/mL for different L.
      monocytogenes strains. Treatment with TFPR induced a decrease of the
      intracellular ATP concentration, an increase of the extracellular concentrations
      of potassium and ATP, and the release of cell constituents. A reduction of pHin
      and cell membrane hyperpolarization were observed after treatment. Electron
      microscopic observations showed that the cell membrane structures of L.
      monocytogenes were apparently impaired by TFPR. It is concluded that TFPR could
      destroy the integrity of the cell membrane of L. monocytogenes, leading to a loss
      of cell homeostasis. These findings indicate that TFPR has the potential to be
      used as a food preservative in order to control L. monocytogenes contamination in
      food and reduce the risk of listeriosis.

PMID- 24447174
TI  - HLA typing by next-generation sequencing - getting closer to reality.
AB  - Next generation sequencing (NGS) denotes novel sequencing technologies that
      enable the generation of a large number of clonal sequences in a single
      sequencing run. NGS was initially introduced for whole genome sequencing and for
      quantitation of viral variants or genetic mutations in tumor tissues; more
      recently, the potential for high resolution HLA typing and high throughput
      analyses has been explored. It became clear that the complexity of the HLA system
      implicates new challenges, especially for bioinformatics. From an economical
      point of view, NGS is becoming increasingly attractive for HLA typing
      laboratories currently relying on Sanger based sequencing. Realizing the full
      potential of NGS will require the development of specifically adapted typing
      strategies and software algorithms. In the present review, three laboratories
      that were among the first to perform HLA-typing using different NGS platforms,
      the Roche 454, the Illumina Miseq and the Ion Torrent system, respectively, give
      an overview of these applications and point out advantages and limitations. 

PMID- 24447175
TI  - Improved pan-specific MHC class I peptide-binding predictions using a novel
      representation of the MHC-binding cleft environment.
AB  - Major histocompatibility complex (MHC) molecules play a key role in cell-mediated
      immune responses presenting bounded peptides for recognition by the immune system
      cells. Several in silico methods have been developed to predict the binding
      affinity of a given peptide to a specific MHC molecule. One of the current state
      of-the-art methods for MHC class I is NetMHCpan, which has a core ingredient for
      the representation of the MHC class I molecule using a pseudo-sequence
      representation of the binding cleft amino acid environment. New and large MHC
      peptide-binding data sets are constantly being made available, and also new
      structures of MHC class I molecules with a bound peptide have been published. In
      order to test if the NetMHCpan method can be improved by integrating this novel
      information, we created new pseudo-sequence definitions for the MHC-binding cleft
      environment from sequence and structural analyses of different MHC data sets
      including human leukocyte antigen (HLA), non-human primates (chimpanzee, macaque
      and gorilla) and other animal alleles (cattle, mouse and swine). From these
      constructs, we showed that by focusing on MHC sequence positions found to be
      polymorphic across the MHC molecules used to train the method, the NetMHCpan
      method achieved a significant increase in the predictive performance, in
      particular, of non-human MHCs. This study hence showed that an improved
      performance of MHC-binding methods can be achieved not only by the accumulation
      of more MHC-peptide-binding data but also by a refined definition of the MHC
      binding environment including information from non-human species. 

PMID- 24447176
TI  - Description of a novel KIR3DL1*0050104 allele identified using sequence-based
      techniques.
AB  - KIR3DL1*0050104 allele differs from KIR3DL1*0050101 at nucleotide positions
      6709C>T (intron 5) and 11365A>G (intron 6). 

PMID- 24447177
TI  - Identification of KIR3DL1*0200101 by long-range sequence-based techniques.
AB  - The new KIR3DL1*0200101 differs from KIR3DL1*01502 with 12 single nucleotide
      polymorphisms (SNPs) in two exons and seven introns. 

PMID- 24447178
TI  - Amphoteric nature of Sn in CdS nanowires.
AB  - High-quality CdS nanowires with uniform Sn doping were synthesized using a Sn
      catalyzed chemical vapor deposition method. X-ray diffraction and transmission
      electron microscopy demonstrate the single crystalline wurtzite structure of the
      CdS/Sn nanowires. Both donor and acceptor levels, which originate from the
      amphoteric nature of Sn in II-VI semiconductors, are identified using low
      temperature microphotoluminescence. This self-compensation effect was cross
      examined by gate modulation and temperature-dependent electrical transport
      measurement. They show an overall n-type behavior with relatively low carrier
      concentration and low carrier mobilities. Moreover, two different donor levels
      due to intrinsic and extrinsic doping could be distinguished. They agree well
      with both the electrical and optical data. 

PMID- 24447179
TI  - Dermoscopy to identify biopsy sites before Mohs surgery.

PMID- 24447181
TI  - Hemodynamic benefit of rest and exercise optimization of cardiac
      resynchronization therapy.
AB  - The optimal method of cardiac resynchronization therapy (CRT) optimization is as
      yet unknown. We sought to investigate the responses of optimization at rest and
      on exercise. This 2 stage study involved 59 patients (age 65 +/- 10, 75% male),
      who had all recently undergone successful CRT implantation. In the first stage,
      the 6-month response was compared between 30 individuals who underwent resting
      echocardiographic optimization of CRT [atrioventricular (AV delay) plus
      ventriculo-ventricular delays (VV delay)], compared with the 29 who did not. In
      the second stage, a subset of 37 patients from the original cohort were
      randomized (double-blind) to either resting echocardiographic optimization (n =
      20) or exercise echocardiographic optimization (n = 17) and followed for a
      further 6 months. Clinical and echocardiographic data were collected at each
      stage. Patients undergoing rest optimization demonstrated improvement in almost
      all variables and significantly in B-type natriuretic peptide (BNP) in contrast
      to those without optimization. In a linear regression model, the only significant
      predictor of BNP change was whether an individual underwent resting optimization
      or not (beta = 0.38, P = 0.04). In those undergoing resting optimization, the
      degree of change in AV delay was correlated with improvement in left ventricle
      (LV) end-diastolic volume (r(2)  = 0.33, P < 0.01). Optimization on exercise was
      associated with a significant decrease in 6-minute walk test compared to those
      randomized to rest optimization possibly due to inducing nonoptimization at rest.
      In conclusion, echocardiographic optimization of CRT at rest is superior to no
      optimization or optimization on exercise. Patients with the greatest change in AV
      delay to reach optimal may undergo greater LV remodeling. 

PMID- 24447182
TI  - Benzyl isothiocyanate inhibits HNSCC cell migration and invasion, and sensitizes
      HNSCC cells to cisplatin.
AB  - Metastasis and chemoresistance represent two detrimental events that greatly
      hinder the outcome for those suffering with head and neck squamous cell carcinoma
      (HNSCC). Herein, we investigated benzyl isothiocyanate's (BITC) ability to
      inhibit HNSCC migration and invasion and enhance chemotherapy. Our data suggests
      that treatment with BITC 1) induced significant reductions in the viability of
      multiple HNSCC cell lines tested (HN12, HN8, and HN30) after 24 and 48 h, 2)
      decreased migration and invasion of the HN12 cells in a dose dependent manner,
      and 3) inhibited expression and altered localization of the epithelial
      mesenchymal transition (EMT) marker, vimentin. We also observed that a
      pretreatment of BITC followed by cisplatin treatment 1) induced a greater
      decrease in HN12, HN30, and HN8 cell viability and total cell count than either
      treatment alone and 2) significantly increased apoptosis when compared to either
      treatment alone. Taken together these data suggest that BITC has the capacity to
      inhibit processes involved in metastasis and enhance the effectiveness of
      chemotherapy. Consequently, the results indicate that further investigation,
      including in vivo studies, are warranted.

PMID- 24447183
TI  - A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA
      vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular
      electroporation.
AB  - Haemorrhagic fever with renal syndrome (HFRS) is endemic in Asia, Europe and
      Scandinavia, and is caused by infection with the hantaviruses Hantaan (HTNV),
      Seoul (SEOV), Puumala (PUUV), or Dobrava (DOBV) viruses. We developed candidate
      DNA vaccines for HFRS expressing the Gn and Gc genes of HTNV or PUUV and
      evaluated them in an open-label, single-centre Phase 1 study. Three groups of
      nine participants each were vaccinated on days 0, 28 and 56 with the DNA vaccines
      for HTNV, PUUV, or a mixture of both vaccines using the Ichor Medical Systems
      TriGrid Intramuscular Delivery System. All vaccinations consisted of a total dose
      of 2.0 mg DNA in an injected volume of 1 mL saline. For the combined vaccine, the
      mixture contained equal amounts (1.0 mg) of each DNA vaccine. There were no study
      related serious adverse events. Neutralizing antibody responses were measured by
      a plaque reduction neutralization test. Neutralizing antibody responses were
      detected in five of nine and seven of nine individuals who completed all three
      vaccinations with the HTNV or PUUV DNA vaccines, respectively. In the combined
      vaccine group, seven of the nine volunteers receiving all three vaccinations
      developed neutralizing antibodies to PUUV. The three strongest responders to the
      PUUV vaccine also had strong neutralizing antibody responses to HTNV. These
      results demonstrate that the HTNV and PUUV DNA vaccines delivered by
      electroporation separately or as a mixture are safe. In addition, both vaccines
      were immunogenic, although when mixed together, more participants responded to
      the PUUV than to the HTNV DNA vaccine.

PMID- 24447185
TI  - The early steps in the photocycle of a photosensor protein sensory rhodopsin I
      from Salinibacter ruber.
AB  - Light absorption by the photoreceptor microbial rhodopsin triggers trans-cis
      isomerization of the retinal chromophore surrounded by seven transmembrane alpha
      helices. Sensory rhodopsin I (SRI) is a dual functional photosensory rhodopsin
      both for positive and negative phototaxis in microbes. By making use of the
      highly stable SRI protein from Salinibacter ruber (SrSRI), the early steps in the
      photocycle were studied by time-resolved spectroscopic techniques. All of the
      temporal behaviors of the Sn<-S1 absorption, ground-state bleaching, K
      intermediate absorption, and stimulated emission were observed in the femto- to
      picosecond time region by absorption spectroscopy. The primary process exhibited
      four dynamics similar to other microbial rhodopsins. The first dynamics (tau1 ~
      54 fs) corresponds to the population branching process from the Franck-Condon
      region to the reactive (S1(r)) and nonreactive (S1(nr)) S1 states. The second
      dynamics (tau2 = 0.64 ps) is the isomerization process of the S1(r) state to
      generate the ground-state 13-cis form, and the third dynamics (tau3 = 1.8 ps)
      corresponds to the internal conversion of the S1(nr) state. The fourth component
      (tau3' = 2.5 ps) is assignable to the J-decay (K-formation). This reaction scheme
      was further supported by the results of fluorescence spectroscopy. To investigate
      the protein response(s), the spectral changes of the tryptophan bands were
      monitored by ultraviolet resonance Raman spectroscopy. The intensity change
      following the K formation in the chromophore structure (tau ~ 17 ps) was
      significantly small in SrSRI as compared with other microbial rhodopsins. We also
      analyzed the effect(s) of Cl(-) binding on the ultrafast dynamics of SrSRI.
      Compared with a chloride pump Halorhodopsin, Cl(-) binding to SrSRI was less
      effective for the excited-state dynamics, whereas the binding altered the
      structural changes of tryptophan following the K-formation, which was the
      characteristic feature for SrSRI. On the basis of these results, a primary
      photoreaction scheme of SrSRI together with the role of chloride binding is
      proposed. 

PMID- 24447186
TI  - Social relationships and allostatic load in the MIDUS study.
AB  - OBJECTIVE: This study examines how the social environment is related to
      allostatic load (AL), a multisystem index of biological risk. METHOD: A national
      sample of adults (N = 949) aged 34-84 rated their relationships with spouse,
      family, and friends at 2 time points 10 years apart. At the second time point,
      participants completed a biological protocol in which indices of autonomic,
      hypothalamic-pituitary-adrenal axis, cardiovascular, inflammatory, and metabolic
      function were obtained and used to create an AL summary score. Generalized
      estimating equations were used to examine the associations among 3 aspects of
      social relationships-social support, social negativity, and frequency of social
      contact-and AL. RESULTS: Higher levels of spouse negativity, family negativity,
      friend contact, and network level contact were each associated with higher AL,
      and higher levels of spouse support were associated with lower AL, independent of
      age, sociodemographic factors, and health covariates. Tests for age interactions
      suggested that friend support and network support were each associated with
      higher AL among older adults, but at younger ages there appeared to be no
      association between friend support and AL and a negative association between
      network support and AL. For network negativity, there was a marginal interaction
      such that network negativity was associated with higher AL among younger adults
      but there was no association among older adults. CONCLUSIONS: These findings
      demonstrate that structural and functional aspects of the social environment are
      associated with AL, and extend previous work by demonstrating that these
      associations vary based on the type of relationship assessed and by age.

PMID- 24447187
TI  - Teaching children to cross streets safely: a randomized, controlled trial.
AB  - OBJECTIVE: Child pedestrian injury is a global public health challenge. This
      randomized, controlled trial considered comparative efficacy of individualized
      streetside training, training in a virtual pedestrian environment, training using
      videos and Web sites, plus no-training control, to improve children's street
      crossing ability. METHODS: Pedestrian safety was evaluated among 231 7- and 8
      year-olds using both streetside (field) and laboratory-based (virtual
      environment) trials before intervention group assignment, immediately
      posttraining, and 6 months posttraining. All training groups received 6 30-min
      sessions. Four outcomes assessed pedestrian safety: start delay (temporal lag
      before initiating crossing), hits/close calls (collisions/near-misses with
      vehicles in simulated crossings), attention to traffic (looks left and right,
      controlled for time), and missed opportunities (safe crossing opportunities that
      were missed). RESULTS: Results showed training in the virtual pedestrian
      environment and especially individualized streetside training resulted in safer
      pedestrian behavior postintervention and at follow-up. As examples, children
      trained streetside entered safe traffic gaps more quickly posttraining than
      control group children and children trained streetside or in the virtual
      environment had somewhat fewer hits/close calls in postintervention VR trials.
      Children showed minimal change in attention to traffic posttraining. Children
      trained with videos/websites showed minimal learning. CONCLUSION: Both
      individualized streetside training and training within virtual pedestrian
      environments may improve 7- and 8-year-olds' street-crossing safety.
      Individualized training has limitations of adult time and labor. Virtual
      environment training has limitations of accessibility and cost. Given the public
      health burden of child pedestrian injuries, future research should explore
      innovative strategies for effective training that can be broadly disseminated.

PMID- 24447188
TI  - New English and Spanish social health measures will facilitate evaluating health
      determinants.
AB  - OBJECTIVE: To develop psychometrically sound, culturally relevant, and
      linguistically equivalent English and Spanish self-report measures of social
      health guided by a comprehensive conceptual model and applicable across chronic
      illnesses. METHODS: The Patient-Reported Outcomes Measurement Information System
      (PROMIS) Social Health Workgroup implemented a mixed methods approach to evaluate
      earlier results (v1.0); expand and refine domain definitions and items; translate
      items into Spanish; and obtain qualitative feedback. Computer-based and
      paper/pencil questionnaire administration was conducted with a variety of U.S.
      respondent samples during 2009-2012. Analyses included exploratory factor
      analysis (EFA), confirmatory factor analysis (CFA), two-parameter logistic item
      response theory (IRT) modeling, evaluation of differential item functioning
      (DIF), and evaluation of criterion and construct validity. RESULTS: Qualitative
      feedback supported the conceptualization of the Social Health domain framework
      (Social Function and Social Relationships subcomponents). Validation testing
      participants (n = 2,208 English; n = 644 Spanish) were diverse in terms of
      gender, age, education, and ethnicity/race. EFA, CFA, and IRT identified 7
      unidimensional factors with good model fit. There was no DIF by language, and
      good evidence of criterion and construct validity. CONCLUSIONS: PROMIS English
      and Spanish language instruments (v2.0), including computer-adaptive tests and
      fixed-length short forms, are publicly available for assessment of Social
      Function (Ability to Participate in Social Roles and Activities, and Satisfaction
      with Social Roles and Activities) and Social Relationships (Companionship;
      Emotional, Informational and Instrumental Support; and Social Isolation).
      Measures of social health will play a key role in applications that use ecologic
      (or determinants of health) models that emphasize how patients' social
      environments influence their health.

PMID- 24447190
TI  - Trait and state disgust: an experimental investigation of disgust and avoidance
      in colorectal cancer decision scenarios.
AB  - OBJECTIVE: To evaluate whether trait and experimentally manipulated state disgust
      independently and/or interactively predict immediate and anticipated avoidance in
      decision scenarios related to colorectal cancer (CRC). METHOD: Eighty
      participants, aged 18 to 66 years, completed questionnaires assessing trait
      disgust prior to a laboratory session. Participants were gender block randomized
      to disgust or control conditions before completing tasks assessing immediate
      avoidance of a CRC disgust elicitor (stoma bag) and anticipated avoidance in
      hypothetical CRC scenarios. RESULTS: Manipulation checks confirmed the
      elicitation of disgust in the experimental condition. Persons in the experimental
      condition were more likely to exhibit immediate avoidance behaviors in response
      to a commonly used bowel disease device (stoma bag), and trait disgust predicted
      time to touch the device. Trait disgust also moderated the influence of state
      disgust on anticipated avoidance, namely delay in help seeking for bowel symptoms
      and predicted rating disgusting side effects as more deterring to adherence.
      CONCLUSIONS: The current report suggests the importance of examining disgust in
      CRC contexts and provides the first empirical demonstration that state and trait
      aspects of disgust may interactively operate to deter certain types of decisions.
      It thus furthers understanding of emotions and avoidance in a health context that
      has had surprisingly little focus to date.

PMID- 24447189
TI  - Pregnancy-specific stress, preterm birth, and gestational age among high-risk
      young women.
AB  - OBJECTIVE: There is evidence that pregnancy-specific stress is associated with
      preterm birth. The purpose of this study is to examine the association between
      change in pregnancy-specific stress over the course of pregnancy and birth
      outcomes (i.e., preterm birth and gestational age) in an understudied but
      vulnerable group using a theoretically derived model. METHODS: Multivariate
      linear and logistic regression techniques were used to examine the association
      between pregnancy-specific stress (measured in second and third trimester) and
      length of gestation (i.e., preterm birth and gestational age) among a sample of
      920 Black and/or Latina adolescent and young women. RESULTS: Second trimester
      pregnancy-specific stress was not associated with preterm birth or gestational
      age. Third trimester pregnancy-specific stress was associated with preterm birth
      but not with gestational age. Change in pregnancy-specific stress between second
      and third trimester was significantly associated with increased likelihood of
      preterm delivery and shortened gestational age, even after controlling for
      important biological, behavioral, psychological, interpersonal, and sociocultural
      risk factors. CONCLUSIONS: Findings emphasize the importance of measuring
      pregnancy-specific stress across pregnancy, as the longitudinal change from
      second to third trimester was significantly associated with length of gestation
      measured both as a dichotomous variable (preterm birth) and a continuous variable
      (gestational age). Furthermore, this is the first study to observe the
      association of pregnancy-specific stress with length of gestation in this
      understudied population-unique in age, race, and ethnicity.

PMID- 24447191
TI  - Activity disruption and depressive symptoms in women living with metastatic
      breast cancer.
AB  - OBJECTIVE: Women with breast cancer are at increased risk of depression, and the
      extent to which valued activities are disrupted by one's illness has been
      correlated with depressive symptoms in women with early stage breast cancer. This
      association has not been examined in women with Stage IV (metastatic) cancer, and
      the temporal directionality of this relationship remains unclear. The goal of the
      current study was to examine longitudinal, reciprocal relationships between
      illness-related disruption of social and recreational activities and self
      reported symptoms of depression in a sample of women living with Stage IV breast
      cancer. METHOD: Participants were 103 women diagnosed with metastatic breast
      cancer. Women completed measures of depressive symptoms and activity disruption
      at study entry (T1) and at 3-month follow-up (T2). RESULTS: Activity disruption
      at study entry did not significantly predict changes in total depressive symptoms
      or in negative affective or somatic symptoms but did predict reductions in
      positive affect. Total depressive symptoms at study entry predicted increases in
      activity disruption, as did negative affective symptoms. CONCLUSIONS: Depressive
      symptoms, specifically negative affective symptoms such as sadness, may
      exacerbate social and recreational activity disruption in women with metastatic
      breast cancer. Cancer-related activity disruption may, in turn, result in
      reductions in positive affect. These results highlight the importance of
      examining specific constellations of depressive symptoms and suggest that
      maintaining valued activities may help to preserve enjoyment of life for patients
      with Stage IV cancer.

PMID- 24447192
TI  - Spousal protective buffering and type 2 diabetes outcomes.
AB  - OBJECTIVE: Guided by the developmental-contextual model of couples coping with
      chronic illness (Berg & Upchurch, 2007), the purpose of this study is to explore
      moderated associations between spousal protective buffering and illness outcomes
      for partners diagnosed with type 2 diabetes (dietary adherence, frequency of
      exercise, and HbA1c level). Patient diabetes appraisals (distress, control, self
      efficacy, and consequences) were explored as potential moderators. METHODS:
      Participants were 117 married couples in which one member had been diagnosed with
      type 2 diabetes. Data were gathered from spouses and patients through a survey
      instrument and analyzed with path analysis. RESULTS: Protective buffering was
      associated with fewer days of exercise when patients reported low diabetes
      distress and diabetes consequences. Additionally, protective buffering was
      associated with higher HbA1c when patients reported high diabetes control.
      CONCLUSIONS: Protective buffering did not exhibit a uniform association with the
      type 2 diabetes outcomes. Rather, the association between spousal protective
      buffering and patient illness adjustment was dependent on patient appraisal of
      the illness. These findings contribute a nuanced addition to the literature
      documenting the role of couple coping in chronic illness management and also
      provide impetus for further, longitudinal investigation of the ways healthy
      spouses cope with partner illness.

PMID- 24447193
TI  - The phoenix rises: a new science of in vivo drug metabolism. Preface.

PMID- 24447194
TI  - Complete chemical shift assignment of the ssDNA in the filamentous bacteriophage
      fd reports on its conformation and on its interface with the capsid shell.
AB  - The fd bacteriophage is a filamentous virus consisting of a circular single
      stranded DNA (ssDNA) wrapped by thousands of copies of a major coat protein
      subunit (the capsid). The coat protein subunits are mostly alpha-helical and
      curved, and are arranged in the capsid in consecutive pentamers related by a
      translation along the main viral axis and a rotation of ~36 degrees  (C5S2
      symmetry). The DNA is right-handed and helical, but information on its structure
      and on its interface with the capsid is incomplete. We present here an approach
      for assigning the DNA nucleotides and studying its interactions with the capsid
      by magic-angle spinning solid-state NMR. Capsid contacts with the ssDNA are
      obtained using a two-dimensional (13)C-(13)C correlation experiment and a proton
      mediated (31)P-(13)C polarization transfer experiment, both acquired on an
      aromatic-unlabeled phage sample. Our results allow us to map the residues that
      face the interior of the capsid and to show that the ssDNA-capsid interactions
      are sustained mainly by electrostatic interactions between the positively charged
      lysine side chains and the phosphate backbone. The use of natural abundance
      aromatic amino acids in the growth media facilitated the complete assignment of
      the four nucleotides and the observation of internucleotide contacts. Using
      chemical shift analysis, our study shows that structural features of the
      deoxyribose carbons reporting on the sugar pucker are strikingly similar to those
      observed recently for the Pf1 phage. However, the ssDNA-protein interface is
      different, and chemical shift markers of base pairing are different. This
      experimental approach can be utilized in other filamentous and icosahedral
      bacteriophages, and also in other biomolecular complexes involving structurally
      and functionally important DNA-protein interactions.

PMID- 24447195
TI  - Influence of different narrative instructions to record the occlusal contact with
      silicone registration materials.
AB  - This study examined the influence of narrative instructions on the occlusal
      contact area, occlusal contact point and masticatory muscle activities in normal
      subjects. Twelve healthy men and 12 healthy women with no more than one missing
      tooth per quadrant participated. Surface EMG was recorded from the masseter and
      temporal muscle. As a control measurement, intercuspal position was maintained to
      produce a habitual clenching record (NCR) while the occlusal contact area and
      occlusal contact point was recorded by means of silicone material. Subsequently,
      the occlusal contact area was recorded with the narrative instruction for minimum
      clenching record (MCR), light clenching record (LCR) and strong clenching record
      (HCR). While the EMG activity (%MVC) increased modestly from MCR to LCR (from 9.3
      +/- 2.0% to 11.5 +/- 1.5%), the occlusal contact area increased rapidly (from
      17.2 +/- 11.3 mm(2) to 26.8 +/- 15.6 mm(2) ) (P < 0.05). Both EMG activity and
      occlusal contact area increased gradually from LCR to NCR (to 17.7 +/- 2.0% and
      to 31.4 +/- 14.2 mm(2) , respectively). Finally, EMG activity still increased
      from NCR to HCR (to 44.5 +/- 3.7%) (P < 0.05), but the occlusal contact area
      remained stable (to 36.8 +/- 16.6 mm(2) ). Occlusal contact points at left
      posterior, right posterior, anterior and total area were not significantly
      different between each task. This study showed that narrative instructions while
      recording the bite can result in largely stable occlusal contact area. An
      adequate narrative instruction may therefore contribute to taking a stable
      occlusal recording in natural dentition. 

PMID- 24447196
TI  - Stereoselective synthesis of indoline, tetrahydroquinoline, and
      tetrahydrobenzazepine derivatives from o-bromophenyl N-tert-butylsulfinyl
      aldimines.
AB  - The diastereoselective addition of an allylic indium intermediate to chiral o
      bromophenyl sulfinyl imine 4 proceeded with good levels of diastereoselectivity.
      The resulting homoallylic amine derivatives were transformed into lactams 7 and
      12, which upon copper-mediated intramolecular N-arylation led to the formation of
      benzo-fused 1-azabicyclo[j.k.0]alkanes 8 and 13. Benzo-fused 2-allyl-substituted
      heterocycles 14 could also be prepared by means of a palladium-catalyzed N
      arylation of the corresponding free amines. The synthesis of the alkaloid (-)
      angustureine was easily accomplished from (S)-2-allyltetrahydroquinoline (14b).

PMID- 24447198
TI  - Omega-3 fatty acids influence mood in healthy and depressed individuals.
AB  - Depression is one of the most prevalent disorders in the United States, and rates
      of depression are higher for women than men. Despite their widespread use, drugs
      used in the treatment of depression are only moderately more effective than
      placebo in treating the disorder. Effective treatment of perinatal depression is
      of particular concern as treatment can influence both the mother and the
      developing child. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation
      may reduce symptoms of major depressive disorder and perinatal depression. The
      aim of the present review was to evaluate epidemiological studies examining PUFA
      intake and depressive symptoms in the general population, as well as double
      blind, placebo-controlled trials assessing the influence of n-3 PUFA in healthy
      individuals and those with depression; specific consideration was given to
      perinatal depression and potential gender differences in the relationship.
      Although there is some evidence to suggest that n-3 PUFA intake is associated
      with reduced depressive symptoms, particularly in females, these results are
      generally limited to epidemiological studies, whereas results from randomized
      controlled trials are mixed. 

PMID- 24447197
TI  - Designing inhibitors of anthrax toxin.
AB  - INTRODUCTION: Present-day rational drug design approaches are based on exploiting
      unique features of the target biomolecules, small- or macromolecule drug
      candidates and physical forces that govern their interactions. The 2013 Nobel
      Prize in chemistry awarded 'for the development of multiscale models for complex
      chemical systems' once again demonstrated the importance of the tailored drug
      discovery that reduces the role of the trial-and-error approach to a minimum. The
      intentional dissemination of Bacillus anthracis spores in 2001 via the so-called
      anthrax letters has led to increased efforts, politically and scientifically, to
      develop medical countermeasures that will protect people from the threat of
      anthrax bioterrorism. AREAS COVERED: This article provides an overview of the
      recent rational drug design approaches for discovering inhibitors of anthrax
      toxin. The review also directs the readers to the vast literature on the
      recognized advances and future possibilities in the field. EXPERT OPINION:
      Existing options to combat anthrax toxin lethality are limited. With the only
      anthrax toxin inhibiting therapy (protective antigen-targeting with a monoclonal
      antibody, raxibacumab) approved to treat inhalational anthrax, the situation, in
      our view, is still insecure. Further, the FDA's animal rule for drug approval,
      which clears compounds without validated efficacy studies on humans, creates a
      high level of uncertainty, especially when a well-characterized animal model does
      not exist. Better identification and validation of anthrax toxin therapeutic
      targets at the molecular level as well as elucidation of the parameters
      determining the corresponding therapeutic windows are still necessary for more
      effective therapeutic options.

PMID- 24447201
TI  - Growth of large single-crystalline two-dimensional boron nitride hexagons on
      electropolished copper.
AB  - Hexagonal-boron nitride (h-BN) or "white graphene" has many outstanding
      properties including high thermal conductivity, high mechanical strength,
      chemical inertness, and high electrical resistance, which open up a wide range of
      applications such as thermal interface material, protective coatings, and
      dielectric in nanoelectronics that easily exceed the current advertised benefits
      pertaining to the graphene-based applications. The development of h-BN films
      using chemical vapor deposition (CVD) has thus far led into nucleation of
      triangular or asymmetric diamond shapes on different metallic surfaces.
      Additionally, the average size of the triangular domains has remained relatively
      small (~ 0.5 MUm(2)) leading to a large number of grain boundaries and defects.
      While the morphology of Cu surfaces for CVD-grown graphene may have impacts on
      the nucleation density, domain sizes, thickness, and uniformity, the effects of
      the decreased roughness of Cu surface to develop h-BN films are unknown. Here, we
      report the growth and characterization of novel large area h-BN hexagons using
      highly electropolished Cu substrate under atmospheric pressure CVD conditions. We
      found that the nucleation density of h-BN is significantly reduced while domain
      sizes increase. In this study, the largest hexagonal-shape h-BN domain observed
      is 35 MUm(2), which is an order of magnitude larger than a typical triangular
      domain. As the domains coalesce to form a continuous film, the larger grain size
      offers a more pristine and smoother film with lesser grain boundaries induced
      defects.

PMID- 24447199
TI  - Global nutrition research: nutrition and breast cancer prevention as a model.
AB  - The gene-environment interaction is paramount in light of the worldwide rise in
      incidence of chronic diseases, with cancers in the pole position. Diet is an
      environmental factor with potential to influence cancer onset by shaping the
      epigenome (i.e., the genome organization that controls the differential
      expression of genes). Yet, there is no consensus regarding how diet might help
      prevent breast cancer, the second most frequent malignancy globally. The
      complexity of breast cancers requires working on a global and multidisciplinary
      scale to further understand the relationship between breast cancer type, diet,
      and the epigenome. This article describes the International Breast Cancer &
      Nutrition collaboration as one such approach. A global endeavor brings the
      diversity necessary to pinpoint important diet-gene relationships. Being
      developed are models, detection and assessment tools, and funding and public
      policy frameworks necessary to advance primary prevention research for the
      benefit of all populations affected by breast cancer. This paradigm can be
      adapted to understanding diet-gene relationships for other chronic diseases. 

PMID- 24447202
TI  - Sudden visual loss and multiple cerebral infarction after autologous fat
      injection into the glabella.

PMID- 24447203
TI  - Lymphadenectomy in surgical stage I epithelial ovarian cancer.
AB  - OBJECTIVE: To identify the extent of lymphadenectomy performed in women
      presenting with epithelial ovarian cancer macroscopically confined to the ovary.
      Furthermore, the effect of lymphadenectomy on overall survival is evaluated.
      DESIGN: A prospective nationwide case-only study. SETTING: Denmark 2005-2011.
      SAMPLE: All women registered in the nationwide Danish Gynecologic Cancer Database
      from 1 January 2005 to 1 May 2011, presenting with a tumor macroscopically
      confined to the ovary without visible evidence of abdominal spread at the time of
      the initial exploration (surgical stage I). METHOD: Descriptive and survival
      analyses of data from Danish Gynecologic Cancer Database. MAIN OUTCOME MEASURES:
      The annual proportion of women with surgical stage I disease who received
      lymphadenectomy and the survival in the two groups. RESULTS: Of 2361 women with
      epithelial ovarian cancer, 627 were identified with surgical stage I.
      Lymphadenectomy was performed in 216 women (34%) of whom 13 (6%) had lymph node
      metastases. At 5-year follow up 85% remained alive in the lymphadenectomy group
      compared with 80% in the control group (p = 0.064). The lymphadenectomy fraction
      increased from 24% in 2005 to 55% in 2011. When univariate and multivariate
      analyses were conducted only an insignificant difference in the survival
      probability was found between lymphadenectomy and no lymphadenectomy in women
      presenting with tumor macroscopically confined to the ovary. CONCLUSION: Although
      increasing, the number of women with surgical stage I disease in Denmark who
      receive lymphadenectomy remains low, but this did not seem to make a difference
      to survival.

PMID- 24447206
TI  - Exploring postoperative outcomes for ingrown toenails. NaOH vs wedge resection
      techniques.
AB  - BACKGROUND: Ingrown (or ingrowing) toenail is a commonly used term for
      onychocryptosis, in which the nail becomes inserted into the lateral fold of the
      toe. The resulting effect on a person's health, well-being, and ability to work
      suggests the importance of clear treatment guidance, but little consensus exists.
      OBJECTIVE: To explore postoperative recovery after surgery for ingrown toenails
      using chemical (sodium hydroxide (NaOH)) or mechanical (wedge resection)
      matricectomy and thus contribute to understanding within the field on which to
      base treatment guidelines. METHODS: One hundred sixty-one procedures were
      undertaken, 94 using NaOH and 67 using wedge resection. Four measures of
      postoperative recovery were recorded: recurrence, infection, time to discharge,
      and number of postoperative visits. RESULTS: Patients treated with NaOH had lower
      rates of recurrence (p = .048) and infection (p = .03) than those treated with
      wedge resection, and time to discharge was shorter (p = .02), but they had more
      postoperative visits (p = .003). CONCLUSION: Low rates of recurrence and
      infection and short postoperative recovery time were found after both procedures,
      with a small advantage with treatment with NaOH. The authors argue for the value
      of clinical intervention using matricectomy in early stages to avoid
      complications resulting from granulation tissue growth.

PMID- 24447207
TI  - Potential intakes of total polyols based on UK usage survey data.
AB  - Polyols are approved for use as sweeteners in specific foods but they may be used
      for other technological purposes in a wider range of foods, all on a quantum
      satis basis. The European Polyols Association (EPA) has identified 24 categories
      of food where polyols are used and it has been able to establish the levels at
      which the polyols are used in each type of food and whether for sweetening or non
      sweetening purposes. The UK National Dietary and Nutrition survey database was
      used to estimate potential exposures to total polyols based on reported use
      levels. It was possible to express potential polyol intake on the basis of
      exposure relating to a single eating occasion, a meal period, 1 day and the
      average over 4 days of the survey. Potential intakes of polyols were
      approximately twice that found on a per-item or a meal-period basis when
      estimated on a daily basis. Apparent intakes were lower when averaged over the 4
      days of the survey. It was felt that intake expressed on a per-meal occasion
      basis was most relevant to the development of digestive discomfort. On the basis
      of maximum use levels of polyols in all food categories, adults had the highest
      intake of total polyols up to 5.6 g per meal period at the 95th percentile.
      However, when expressed on a bodyweight basis, children had higher intakes, up to
      0.15 g kg(-1) bw per meal period. Distributions of potential polyol exposures
      were highly skewed towards lower values with higher levels of exposure relating
      to sweetener uses occurring relatively infrequently.

PMID- 24447208
TI  - Design, synthesis, and conformational analysis of trispyrimidonamides as alpha
      helix mimetics.
AB  - The straightforward synthesis of trispyrimidonamides as a new class of alpha
      helix mimetics is reported. Because of the versatility of our synthetic protocol,
      a variety of side chains including aliphatic, basic, aromatic, and heteroaromatic
      residues were included. A comprehensive conformational analysis revealed that in
      polar solvents a trimeric compound adopts conformations that can lead to i, i +
      4, i + 8, or i, i + 8 patterns of side chain orientation. This suggests that
      trispyrimidonamides could be promising alpha-helix mimetics to target hot spots
      that are distributed over a wider angular range of an alpha-helix interface than
      in the classical i, i + 4, i + 7 case.

PMID- 24447209
TI  - Mini-review: impact and dynamics of surface fouling by solitary and compound
      ascidians.
AB  - Globally, ascidians are a significant contributor to benthic marine fouling
      communities, but have remained poorly studied in this context. In some cases,
      such as in shellfish and finfish aquaculture, ascidians are the most problematic
      of all fouling organisms. The disproportionate impact of ascidian fouling in some
      specific geographic locations has been related directly to anthropogenic
      translocation of these organisms around the globe. In the case of ascidians,
      therefore, the economic issue of biofouling and the ecological ramifications of
      invasion are inextricably linked. This mini-review briefly discusses the
      introduction of non-native ascidians to areas where they have subsequently proven
      to be a significant fouling pest. The elements of ascidian reproductive ecology
      that support their aggressive fouling character are discussed and the scant
      information pertaining to their adhesion and adhesives is presented. Finally,
      strategies for mitigating ascidian fouling are examined. It is suggested that
      sufficient working knowledge currently exists to support the inclusion of one or
      more common ascidian species as 'standard' test organisms used for evaluation of
      novel fouling-resistant surfaces. 

PMID- 24447210
TI  - Lung response after subchronic glass fiber intratracheal instillation: an
      experimental study on rats.
AB  - The aim of the study was to identify the effects on the lung after subchronic
      glass fiber intratracheal instillation study on rats. We evaluated the
      toxicological effects on the lung: persistent inflammatory reaction, cell
      proliferation, and pulmonary fibrosis on histopathological examination. We
      performed a glass fiber intratracheal instillation study on total 32 Wistar rats.
      The animals were divided into four groups: three test groups exposed to different
      doses of glass fiber and one control group. One week after the end of the
      exposure period, all animals were euthanized. The histopathological examination
      of the lung performed in this study followed both distribution of the lesions
      through the multilevel biopsies that were taken and the inflammatory profile
      using both hematoxilin-eozin and Sirius red staining. The inflammatory lesions
      described for the first group were minimal/slight (grade I) and the total score
      was between 0 and 10 points (mean value = 3). For the second group, the
      inflammatory lesions were moderate/marked (grade II) with discrete collagen
      proliferation and discrete fibrosis and the total score ranged between 11 and 20
      points (mean value = 11,250). For the third group, the described inflammatory
      lesions were massive with total score ranging between 21 and 30 points with
      collagen deposition, pulmonary and pleural fibrosis, and lung emphysema (mean
      value = 21,750) and no lesion in control group (with statistically significant
      difference P <= .001). This study of fiber glass intratracheal instillation of
      three different doses demonstrates that exposure to fiber glass is responsible
      for the development of persistent inflammatory response and a large range of
      hystopathological lesions which correlate to the administered dose.

PMID- 24447211
TI  - The global burden of conduct disorder and attention-deficit/hyperactivity
      disorder in 2010.
AB  - OBJECTIVE: The Global Burden of Disease Study 2010 (GBD 2010) is the first to
      include conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD)
      for burden quantification. METHOD: A previous systematic review pooled the
      available epidemiological data for CD and ADHD, and predicted prevalence by
      country, region, age and sex for each disorder. Prevalence was then multiplied by
      a disability weight to calculate years lived with disability (YLDs). As no
      evidence of deaths resulting directly from either CD or ADHD was found, no years
      of life lost (YLLs) were calculated. Therefore, the number of disability-adjusted
      life years (DALYs) was equal to that of YLDs. RESULTS: Globally, CD was
      responsible for 5.75 million YLDs/DALYs with ADHD responsible for a further
      491,500. Collectively, CD and ADHD accounted for 0.80% of total global YLDs and
      0.25% of total global DALYs. In terms of global DALYs, CD was the 72nd leading
      contributor and among the 15 leading causes in children aged 5-19 years. Between
      1990 and 2010, global DALYs attributable to CD and ADHD remained stable after
      accounting for population growth and ageing. CONCLUSIONS: The global burden of CD
      and ADHD is significant, particularly in male children. Appropriate allocation of
      resources to address the high morbidity associated with CD and ADHD is necessary
      to reduce global burden. However, burden estimation was limited by data lacking
      for all four epidemiological parameters and by methodological challenges in
      quantifying disability. Future studies need to address these limitations in order
      to increase the accuracy of burden quantification.

PMID- 24447214
TI  - Microwave synthesis, photoluminescence, and photocatalytic activity of PVA
      functionalized Eu3+-doped BiOX (X = Cl, Br, I) nanoflakes.
AB  - We report a facile microwave-assisted green synthetic route for colloidal
      poly(vinyl alcohol) (PVA)-coated europium (Eu(3+))-doped luminescent heavy metal
      bismuth oxyhalide (BiOX; X = Cl, Br, I) nanoflakes at low temperature and examine
      their structural, optical, and photocatalytic characteristics. PVA coating onto
      the surface of the nanoflakes endows them with hydrophilic nature. Both Eu(3+)
      doped BiOCl and BiOBr nanoflakes exhibit strong optical properties related to
      Eu(3+) and Bi(3+) which are quenched in case of Eu(3+)-doped BiOI matrix. These
      results are supported by Eu(3+) photoluminescence lifetime values of 0.61 ms,
      0.59 ms, and 8.9 MUs, respectively. The former two matrices have quite similar
      crystal field environments as deduced from the asymmetric ratios of (5)D0 ->
      (7)F2 (614 nm) and (5)D0 -> (7)F1 (591 nm) transitions. In addition to possessing
      interesting photoluminescence properties, a comparison of the photocatalytic
      activity of Eu(3+)-doped BiOX (X = Cl, Br, I) nanoflakes, with corresponding
      estimated band gaps of 3.36, 2.74, and 1.67 eV has been evaluated using Rhodamine
      B (RhB) dye under visible light irradiation. The nanoflakes exhibited 100% dye
      degradation under visible light irradiation. Eu(3+)-doped BiOCl nanoflakes
      manifested higher photocatalytic efficiency compared to the other matrices
      following apparent first-order kinetics. Such a boost in efficiency is attributed
      to their high surface area to volume ratios, layered crystalline structures,
      indirect band gap nature, and ability to utilize broad bands in the solar
      spectrum. 

PMID- 24447212
TI  - Comparison of porcine endogenous retroviruses infectious potential in
      supernatants of producer cells and in cocultures.
AB  - BACKGROUND: Porcine endogenous retroviruses (PERV) pose a zoonotic risk potential
      in pig-to-human xenotransplantation given that PERV capacity to infect different
      human cell lines in vitro has been clearly shown in the past. However, PERV
      infectious potential for human peripheral blood mononuclear cells (huPBMC) has
      been also demonstrated, albeit with controversial results. As productive PERV
      infection of huPBMC involves immune suppression that may attract opportunistic
      pathogens as shown for other retroviruses, it is crucial to ascertain
      unequivocally huPBMC susceptibility for PERV. To address this question, we first
      investigated in vitro infectivity of PERV for huPBMC using supernatants
      containing highly infectious PERV-A/C. Second, huPBMC were cocultivated with PERV
      A/C producer cells to come a step closer to the in vivo situation of
      xenotransplantation. In addition, cocultivation of huPBMC with porcine PBMC
      (poPBMC) isolated from German landrace pigs was performed to distinguish PERV
      replication competence when they were constitutively produced by immortalized
      cells or by primary poPBMC. METHODS: Supernatants containing recombinant highly
      infectious PERV-A/C were used to infect PHA-activated huPBMC in the presence or
      absence of polybrene. Next, PERV-producing cell lines such as human 293/5 degrees
      and primary mitogenically activated poPBMC of three German landrace pigs were
      cocultivated with huPBMC as well as with susceptible human and porcine cell lines
      as controls. PERV infection was monitored by using three test approaches. The
      presence of provirus DNA in putatively infected cells was detected via sensitive
      nested PCR. Viral expression was determined by screening for the activity of
      gammaretroviral reverse transcriptase (RT) in cell-free supernatants of infected
      cells. Virus release was monitored by counting the number of packaged RNA
      particles in supernatants via PERV-specific quantitative one-step real-time
      reverse transcriptase PCR. RESULTS: Porcine endogenous retroviruses-A/C in
      supernatants of human producer 293/5 degrees  cells was not able to infect
      huPBMC. Neither RT activity nor PERV copies were detected. Even provirus could
      not be detected displaying the inability of PERV-A/C to induce a productive
      infection in huPBMC. In cocultivation experiments only non-productive infection
      of huPBMC with PERV derived from 293/5 degrees  cell line and from PHA-activated
      poPBMC was observed by detection of provirus DNA in infected cells. CONCLUSION:
      Recombinant PERV-A/C in supernatants of producer cells failed to infect huPBMC,
      whereas coculture experiments with producer cell lines lead to non-productive
      infection of huPBMC. PERV in supernatants seem to have not sufficient infectious
      potential for huPBMC. However, extensive PERV exposure to huPBMC via
      cocultivation enabled at least virus cell entry as provirus was detected by
      nested PCR. Furthermore, results presented support previous data showing German
      landrace pigs as low producers with negligible infectious potential due to the
      absence of replication-competent PERV in the genome. The low PERV expression
      profile and the lack of significant replication competence of German landrace
      pigs raise hope for considering these animals as putative donor animals in future
      pig-to-human xenotransplantation. Nonetheless, data imply that PERV still
      represent a virological risk in the course of xenotransplantation, as the
      presence of PERV provirus in host cells may lead to a provirus integration
      resulting in insertional mutagenesis and chromosomal rearrangements.

PMID- 24447215
TI  - Surface freezing and molecular miscibility of binary alkane-alkane and
      fluoroalkane-alkane liquid mixtures.
AB  - The surface freezing (SF) of liquid n-heptadecane (C17)-n-octadecane (C18) and 1
      perfluorooctyl decane (F8H10)-C18 mixtures were studied by surface tension and
      external reflection absorption FTIR (ERA-FTIR) measurements. The surface tension
      versus temperature curves of all pure liquids show a sharp break point at Ts
      corresponding to a surface liquid (SL)-SF transition. The entropy of surface
      formation is very negative, indicating a well-ordered structure of the SF layer.
      The ERA-FTIR spectra in the SF state suggested that the C18 molecules are densely
      packed in the solid state, while the packing of the hydrocarbon (HC) part of
      F8H10 is a little looser than the fluorocarbon (FC) part because of the
      difference in the cross-sectional area. In the C17-C18 mixture, the SL-SF
      transition was found at all bulk compositions. The estimation of the surface
      composition suggested that two components are miscible both in SL and SF states.
      The excess entropy of the surface is almost zero in both states, and thus, it was
      concluded that the two components are mixed almost ideally at the surface. In the
      case of the F8H10-C18 system, on the other hand, the SL layer is enriched in
      F8H10 with lower surface tension than C18 compared to bulk liquid. The surface
      composition in the SF state is almost zero or unity, indicating that F8H10 and
      C18 molecules are practically immiscible mainly due to the weak interaction
      between different components. Furthermore, the negative excess entropy in the SL
      layer suggests domain formation of F8H10 molecules at the surface. 

PMID- 24447216
TI  - A metabolic approach to study algal-bacterial interactions in changing
      environments.
AB  - Increasing evidence exists that bacterial communities interact with and shape the
      biology of algae and that their evolutionary histories are connected. Despite
      these findings, physiological studies were and still are generally carried out
      with axenic or at least antibiotic-treated cultures. Here, we argue that
      considering interactions between algae and associated bacteria is key to
      understanding their biology and evolution. To deal with the complexity of the
      resulting 'holobiont' system, a metabolism-centred approach that uses combined
      metabolic models for algae and associated bacteria is proposed. We believe that
      these models will be valuable tools both to study algal-bacterial interactions
      and to elucidate processes important for the acclimation of the holobiont to
      environmental changes. 

PMID- 24447217
TI  - Motivating and hindering factors during the reemployment process: the added value
      of employment counselors' assessment.
AB  - Because unemployment negatively affects people's well-being, it is of crucial
      importance that unemployed individuals move back to work. The process of getting
      reemployed, however, is difficult and complex. Therefore, many unemployed job
      seekers are assisted by employment counselors. The present study focuses on
      motivating and hindering factors in the reemployment process, examining the added
      value of the counselors' assessment of job seekers' attitudes, perceptions, and
      behaviors. The results of a 3-wave study with job seeker self-ratings and
      counselor-ratings indicated that perceived health problems is the most consistent
      predictor of job search and reemployment status. The findings further provide
      some convergent validity evidence for self- and counselor-rated situational-level
      motivators (i.e., attitude, social pressure, self-efficacy) and job search
      intensity. Although method effects did not seem to threaten the validity of the
      prediction of job search intensity and procrastination, employment counselors'
      assessments of job seekers' job search intensity and procrastination were
      significantly more strongly related to reemployment success than job seekers'
      self-ratings. Future research should therefore include other-reports, in addition
      to job seeker self-reports, to get a more complete view of people's job search
      behavior. Also reemployment counseling firms may want to use the expert knowledge
      of their employment counselors more systematically.

PMID- 24447218
TI  - Achievement goals and autonomy: how person--context interactions predict
      effective functioning and well-being during a career transition.
AB  - This study examined how achievement goals interact with autonomy to explain
      mastery of a challenging career transition. In a sample of women who were
      returning from maternity leave, we examined how autonomy interacted with
      achievement goals to explain two types of outcomes: effective functioning (i.e.,
      self-rated work adjustment, coworker-rated work adjustment, and coworker-rated
      learning competence) and well-being at work (i.e., positive affect and life
      satisfaction). In a longitudinal design (249 employees), we found that
      achievement goals and autonomy had direct effects on successful return to work.
      Moreover, maladaptive motivational states hindered the effective use of workplace
      resources: Autonomy moderated the consequences associated with performance-prove
      and -avoidance goals. Among those who adopted performance-prove goals, autonomy
      improved work adjustment and learning. However, women who adopted performance
      avoidance goals experienced a trade-off between effective functioning and well
      being, when equipped with high autonomy.

PMID- 24447219
TI  - A short and valid measure of work-family enrichment.
AB  - The stream of research concerning work-family enrichment has generated a
      significant body of research because it plays an important role in occupational
      health (Masuda, McNall, Allen, & Nicklin, 2012). work-family enrichment has been
      defined as "the extent to which experiences in one role improve the quality of
      life in the other role" (Greenhaus & Powell, 2006, p. 73). Within work-family
      enrichment, there are two directions: work to family and family to work. Carlson,
      Kacmar, Wayne, and Grzywacz (2006) developed an 18-item scale to measure this
      construct. Although the scale has been shown to be both reliable and valid, it
      also requires work-family researchers to include a proportionally large number of
      items to capture this construct in a study. The goal of the current study was to
      isolate a subset of the items in this measure that produces results similar to
      the full version thereby providing a more streamlined scale for researchers.
      Using a five-sample study that follows the scale reduction procedures offered by
      Stanton, Sinar, Balzer, and Smith (2002), we provide evidence that scales
      containing only three items for each direction of enrichment produce results
      equivalent to the full scale with respect to reliability and discriminant,
      convergent, and predictive validity. Reducing the original scale by two thirds,
      without losing explanatory power, allows scholars to measure enrichment in the
      work and family domains more efficiently, which should help minimize survey time,
      lower refusal rates, and generate less missing data.

PMID- 24447220
TI  - Development and initial validation of a measure of work, family, and school
      conflict.
AB  - This study reports the development and initial validation of a theoretically
      based measure of conflict between work, family, and college student roles. The
      measure was developed through the assessment of construct definitions and an
      assessment of measurement items by subject matter experts. Then, the measurement
      items were assessed with data from 500 college students who were engaged in work
      and family responsibilities. The results indicate that conflict between work,
      family, and school are effectively measured by 12 factors assessing the direction
      of conflict (e.g., work-to-school conflict, and school-to-work conflict) as well
      as the form of conflict (i.e., time, strain, and behavior based conflict). Sets
      of exploratory and confirmatory factor analyses demonstrated that the 12 factors
      of the new measure are distinct from the 6 factors of the Carlson, Kacmar, and
      Williams (2000) work-family conflict measure. Criterion validity of the measure
      was established through a series of regression analyses testing hypothesized
      relationships between antecedent and outcome variables with role conflict.
      Results indicate that role demand was a robust predictor of role conflict. To
      extend the literature, core self-evaluations and emotional stability were
      established as predictors of role conflict. Further, work, family, and school
      role satisfaction were significantly impacted with the presence of role conflict
      between work, family, and school.

PMID- 24447221
TI  - Does being a mom help or hurt? Workplace incivility as a function of motherhood
      status.
AB  - The purpose of the present study was to examine the extent to which motherhood
      status predicts being a target of workplace incivility and moderates the
      relationship between incivility and negative outcomes among employed women.
      Participants included a nationwide sample of law school faculty members (N =
      1,234; 48% female, 85% White) who completed measures of workplace incivility,
      parenting status, job satisfaction, turnover intentions, and depression. Results
      showed that mothers with 3 children were treated more uncivilly than women with
      fewer children and that mothering mitigated negative outcomes associated with
      being the target of incivility. Exploratory analyses examining fatherhood status
      as a predictor of workplace incivility and moderator of incivility and outcomes
      showed that fathers reported experiencing more workplace incivility than
      nonfathers, but being a father did not attenuate the negative outcomes of
      incivility. In addition, mothers reported more incivility than fathers and
      childless women reported more incivility than childless men. Childless women were
      also the most negatively affected by incivility at work. This study advances our
      understanding of how motherhood status affects women's experiences at work.

PMID- 24447222
TI  - A diary study on work-related smartphone use, psychological detachment and
      exhaustion: examining the role of the perceived segmentation norm.
AB  - In this diary study, we examined the associations between daily work-related
      smartphone use and daily psychological detachment and daily work-related
      exhaustion within a group of smartphone owners. In addition, we studied the role
      of the perceived segmentation norm at the workplace as a moderator of the link
      between work-related smartphone use and detachment. A total of 70 employees using
      smartphones on initiative of their employer completed a diary questionnaire on 4
      successive workdays (N = 268 data points). We hypothesized that work-related
      smartphone use is negatively related to psychological detachment and that
      psychological detachment, in turn, is negatively related to work-related
      exhaustion. Finally, we expected that especially employees who perceive a high
      segmentation norm at their workplace have difficulties to psychologically detach
      from work on days that they use their smartphone more intensively. Overall, the
      results of multilevel analyses supported these hypotheses. The findings emphasize
      the importance of a clear organizational policy regarding work-related smartphone
      use outside of work hours.

PMID- 24447223
TI  - Social stressors at work and sleep during weekends: the mediating role of
      psychological detachment.
AB  - Social stressors at work may result in long-term health impairments if recovery
      is insufficient. In the present psychophysiological field study, we tested
      whether the inability to psychologically detach from work issues mediates the
      negative effect of social stressors at work on sleep during weekends. Sixty full
      time employees participated in the study. Daily assessment included diaries on
      psychological detachment and continuous ambulatory actigraphy to assess
      psychophysiological indicators of sleep. Hierarchical regression analyses
      revealed that enduring social stressors at work were negatively related with
      psychological detachment on Sunday evening and negatively related with various
      sleep indicators on Sunday night. Furthermore, psychological detachment from work
      on Sunday evening partially mediated the effect of social stressors at work on
      two sleep indicators. Social stressors at work may threaten recovery processes
      just before the working week starts.

PMID- 24447224
TI  - Burnout and job performance: the moderating role of selection, optimization, and
      compensation strategies.
AB  - The present study aims to explain why research thus far has found only low to
      moderate associations between burnout and performance. We argue that employees
      use adaptive strategies that help them to maintain their performance (i.e., task
      performance, adaptivity to change) at acceptable levels despite experiencing
      burnout (i.e., exhaustion, disengagement). We focus on the strategies included in
      the selective optimization with compensation model. Using a sample of 294
      employees and their supervisors, we found that compensation is the most
      successful strategy in buffering the negative associations of disengagement with
      supervisor-rated task performance and both disengagement and exhaustion with
      supervisor-rated adaptivity to change. In contrast, selection exacerbates the
      negative relationship of exhaustion with supervisor-rated adaptivity to change.
      In total, 42% of the hypothesized interactions proved to be significant. Our
      study uncovers successful and unsuccessful strategies that people use to deal
      with their burnout symptoms in order to achieve satisfactory job performance.

PMID- 24447225
TI  - The role of punishment and reward sensitivity in the emotional labor process: a
      within-person perspective.
AB  - In this diary study, we tested the possibility that dispositional reward and
      punishment sensitivity, two central constructs of reinforcement sensitivity
      theory, would modify the relationship between emotional labor and job-related
      well-being (i.e., work engagement, emotional exhaustion, depersonalization).
      Specifically, based on a social functional account of emotion, we hypothesized
      that surface acting entails the risk of social disapproval and therefore may be
      more detrimental for high than for low punishment-sensitive individuals. In
      contrast, deep acting is hypothesized to hold the promise of social approval and
      therefore may be more beneficial for high than for low reward-sensitive
      individuals. Hypotheses were tested in a sample of 237 service workers (N = 1,584
      daily reports) who completed a general survey and daily surveys over the course
      of 10 working days. Multilevel analyses showed that surface acting was
      detrimental to well-being, and more strongly so for high than for low punishment
      sensitive individuals. The results are consistent with the idea that heightened
      sensitivity to social disapproval aggravates the negative effects of surface
      acting.

PMID- 24447226
TI  - The unique case of foot drop secondary to a large ovarian cyst.
AB  - We describe the unique case of a 58-year-old woman who presented with right leg
      radiculopathy caused by an ovarian cyst mimicking lumbar pathology. A review of
      the literature shows that this is a rare case where a histologically confirmed
      benign ovarian cystadenoma (of indeterminate type) is shown to cause foot drop
      and radiculopathy.

PMID- 24447227
TI  - Is basiliximab induction, a novel risk factor for new onset diabetes after
      transplantation for living donor renal allograft recipients?
AB  - AIM: It was found that, by affecting populations of T lymphocytes and regulatory
      T cells, basiliximab also indirectly affects pancreatic beta-cell function and
      glucose homeostasis. METHODS: In this prospective observational study, we
      included all renal transplant recipients from 1 July 2007 to 31 July 2011. The
      overall incidence of hyperglycaemia (transient hyperglycaemia, impaired fasting
      glucose (IFG), impaired glucose tolerance (IGT) and new onset diabetes after
      transplantation (NODAT)) was compared between patients with and without
      basiliximab induction. RESULTS: Of the 439 eligible study patients, 105 patients
      received basiliximab induction and 334 patients did not. Overall hyperglycaemia
      (transient hyperglycaemia, IFG, IGT and NODAT) was detected in 102/334 (30.5%)
      patients without induction and 44/105 (41.9%) patients with induction (P = 0.03).
      Of the 102 patients with hyperglycaemia in patients without basiliximab, 46
      (45.1%) patients improved, while only 10 (22.7%) of the 44 patients with
      basiliximab improved (P = 0.016) at the end of 3 months. Finally, NODAT was
      observed in 56/334 (16.7%) patients without induction and 102/334 (30.5%)
      patients with induction. Relative risk of NODAT with basiliximab was 2.3 (95% CI
      1.4-3.9) compared to that of patients without induction. Basiliximab and
      hepatitis C virus infection were independent risk factors for NODAT. Risk of
      NODAT remained high with basiliximab despite adjusting the acute rejections
      episodes. CONCLUSIONS: Basiliximab induction prevents acute rejection; however,
      it is associated with increased risk of NODAT.

PMID- 24447228
TI  - Tethering of tricuspid valve resulting from aberrant tendinous cords mimic
      ebstein's anomaly, three-dimensional echocardiography approach.

PMID- 24447229
TI  - Fortification: new findings and implications.
AB  - This article reviews the current landscape regarding food fortification in the
      United States; the content is based on a workshop sponsored by the North American
      Branch of the International Life Sciences Institute. Fortification of the food
      supply with vitamins and minerals is a public health strategy to enhance nutrient
      intakes of the population without increasing caloric intake. Many individuals in
      the United States would not achieve recommended micronutrient intakes without
      fortification of the food supply. The achievement and maintenance of a desirable
      level of nutritional quality in the nation's food supply is, thus, an important
      public health objective. While the addition of nutrients to foods can help
      maintain and improve the overall nutritional quality of diets, indiscriminate
      fortification of foods could result in overfortification or underfortification in
      the food supply and nutrient imbalances in the diets of individuals. Any changes
      in food fortification policy for micronutrients must be considered within the
      context of the impact they will have on all segments of the population and of
      food technology and safety applications and their limitations. This article
      discusses and evaluates the value of fortification, the success of current
      fortification efforts, and the future role of fortification in preventing or
      reversing nutrient inadequacies. 

PMID- 24447230
TI  - Direct observation of a long-lived single-atom catalyst chiseling atomic
      structures in graphene.
AB  - Fabricating stable functional devices at the atomic scale is an ultimate goal of
      nanotechnology. In biological processes, such high-precision operations are
      accomplished by enzymes. A counterpart molecular catalyst that binds to a solid
      state substrate would be highly desirable. Here, we report the direct observation
      of single Si adatoms catalyzing the dissociation of carbon atoms from graphene in
      an aberration-corrected high-resolution transmission electron microscope (HRTEM).
      The single Si atom provides a catalytic wedge for energetic electrons to chisel
      off the graphene lattice, atom by atom, while the Si atom itself is not consumed.
      The products of the chiseling process are atomic-scale features including
      graphene pores and clean edges. Our experimental observations and first
      principles calculations demonstrated the dynamics, stability, and selectivity of
      such a single-atom chisel, which opens up the possibility of fabricating certain
      stable molecular devices by precise modification of materials at the atomic
      scale. 

PMID- 24447231
TI  - An Australian survey of audiologists' preferences for patient-centredness.
AB  - OBJECTIVE: Patient-centredness is becoming a core value of health services
      worldwide, however it remains largely unexplored in audiology. This study
      investigated audiologists' preferences for patient-centredness and identified
      factors that explain audiologists' preferences for patient-centredness. DESIGN:
      All members of the Audiological Society of Australia received two questionnaires:
      (1) a descriptive questionnaire (e.g. age, gender, place of residence, years in
      practice, employment characteristics), and (2) a modified patient-practitioner
      orientation scale (PPOS; Krupat et al, 2000) which measures preferences for two
      aspects of patient-centredness, sharing and caring. STUDY SAMPLE: In total 663
      (46%) audiologists returned both questionnaires fully completed. RESULTS: Mean
      PPOS scores indicated that audiologists prefer patient-centredness. Linear
      regression modelling identified that older audiologists, that had practiced
      longer, and who worked in community education, industrial audiology, or teaching
      had a significantly greater preference for patient-centredness than their peers.
      In contrast, audiologists who practiced in a private environment and who worked
      in the area of assessment of adults had a significantly lesser preference for
      patient-centredness than their peers. CONCLUSIONS: Audiologists prefer client
      centredness and age, years of experience, and employment characteristics can
      partly explain preferences for patient-centredness. Future research should
      explore the relationships between patient-centredness and intervention outcomes
      in audiology.

PMID- 24447232
TI  - Hearing aid user guides: suitability for older adults.
AB  - OBJECTIVE: The aim of this study was to analyse the content, design, and
      readability of printed hearing aid user guides to determine their suitability for
      older adults, who are the main users of hearing aids. DESIGN: Hearing aid user
      guides were assessed using four readability formulae and a standardized tool to
      assess content and design (SAM - Suitability Assessment of Materials). STUDY
      SAMPLE: A sample of 36 hearing aid user guides (four user guides from nine
      different hearing aid manufacturers) were analysed. RESULTS: Sixty nine percent
      of user guides were rated 'not suitable' and 31% were rated 'adequate' for their
      suitability. Many scored poorly for scope, vocabulary, aspects of layout and
      typography, and learning stimulation and motivation. The mean reading grade level
      for all user guides was grade 9.6 which is too high for older adults. CONCLUSION:
      The content, design, and readability of hearing aid user guides are not optimal
      for older adults and thus may serve as a barrier to successful hearing aid
      outcomes for this population.

PMID- 24447233
TI  - Factors associated with success with hearing aids in older adults.
AB  - OBJECTIVE: To examine associations between audiological and non-audiological
      factors and successful hearing aid use in older adults. DESIGN: In a
      retrospective study, audiological factors, attitudinal beliefs (as derived from
      the health belief model), client demographics, psychological factors, and age
      related factors were evaluated. STUDY SAMPLE: Participants included 160
      individuals, 60 years or older, with unilateral or bilateral hearing impairment
      (HI), fitted with hearing aids for the first time in the previous two years.
      Participants were assigned to either an unsuccessful hearing aid owner group
      (n=75) or a successful hearing aid owner group (n=85) based on their self
      reported hearing aid use and benefit. RESULTS: A multivariate, binomial logistic
      regression model indicated five factors associated with group membership:
      participants who had greater support from significant others; more difficulties
      with hearing and communication in everyday life before getting hearing aids; more
      positive attitudes to hearing aids; coupled with greater perceived self-efficacy
      for advanced handling of hearing aids; or who were receiving more gain from their
      devices; were more likely to be successful hearing aid owners. CONCLUSIONS: These
      findings highlight the importance of addressing non-audiological factors in order
      to assist older adults achieve success with hearing aids.

PMID- 24447234
TI  - An Australian version of the acceptable noise level test and its predictive value
      for successful hearing aid use in an older population.
AB  - OBJECTIVE: The acceptable noise level (ANL), a measure of noise tolerance, has
      been proposed as a predictor for successful hearing aid use. The aims of this
      study were to obtain normative data, and to evaluate the clinical feasibility and
      predictive value of an Australian version of the ANL test in an older population.
      DESIGN: Repeated ANL measurements were presented diotically using earphones. All
      participants provided demographic information and hearing aid owners were asked
      about their aid use. STUDY SAMPLE: A total of 290 older adults were assessed; 166
      participants had a hearing impairment and 96 owned a hearing aid. RESULTS: The
      mean ANL was lower than previously reported. While age and gender had no effect
      on ANL, a significant, but weak, correlation was found between ANL and hearing
      loss. The test-retest reliability showed the results were clinically unreliable.
      In addition, the ANL did not predict hours or pattern of hearing aid use.
      CONCLUSIONS: While the Australian ANL test showed several similar characteristics
      to previous versions of the test, low test-retest reliability raised questions
      about its clinical value as a predictor for long-term hearing aid use.

PMID- 24447235
TI  - Identifying the barriers and facilitators to optimal hearing aid self-efficacy.
AB  - OBJECTIVE: Many older adults with hearing impairment are not confident in their
      ability to use hearing aids (i.e. experience low hearing aid self-efficacy),
      which has been found to be a barrier to hearing help-seeking and hearing aid use.
      This study aimed to determine what factors were associated with achieving
      adequate hearing aid self-efficacy. DESIGN: A retrospective research design was
      employed wherein hearing aid self-efficacy was the primary outcome. Explanatory
      variables included personal demographics, visual disability, and experiences
      related to participants' hearing ability and hearing aids. STUDY SAMPLE: A total
      of 307 older adults with hearing impairment participated in the study (147 non
      hearing aid owners and 160 hearing aid owners). RESULTS: Non-hearing aid owners
      were more likely to report adequate hearing aid self-efficacy if they reported no
      visual disability, had experienced hearing loss for longer, reported more
      positive support from a significant other, and were not anxious about wearing
      hearing aids. Hearing aid owners were more likely to report adequate hearing aid
      self-efficacy if they had had a positive hearing aid experience and no visual
      disability. CONCLUSIONS: More research is needed to develop and evaluate
      intervention approaches that promote optimal levels of hearing aid self-efficacy
      among older adults with hearing impairment.

PMID- 24447236
TI  - Patient-centred care: a review for rehabilitative audiologists.
AB  - OBJECTIVE: This discussion paper aims to synthesise the literature on patient
      centred care from a range of health professions and to relate this to the field
      of rehabilitative audiology. Through review of the literature, this paper
      addresses five questions: What is patient-centred care? How is patient-centred
      care measured? What are the outcomes of patient-centred care? What are the
      factors contributing to patient-centred care? What are the implications for
      audiological rehabilitation? DESIGN: Literature review and synthesis. STUDY
      SAMPLE: Publications were identified by structured searches in PubMed, Cinahl,
      Web of Knowledge, and PsychInfo, and by inspecting the reference lists of
      relevant articles. RESULTS: Few publications from within the audiology profession
      address this topic and consequently a review and synthesis of literature from
      other areas of health were used to answer the proposed questions. CONCLUSION:
      This paper concludes that patient-centred care is in line with the aims and scope
      of practice for audiological rehabilitation. However, there is emerging evidence
      that we still need to inform the conceptualisation of patient-centred
      audiological rehabilitation. A definition of patient-centred audiological
      rehabilitation is needed to facilitate studies into the nature and outcomes of it
      in audiological rehabilitation practice.

PMID- 24447237
TI  - General population norms of the Swedish short forms of oral health impact
      profile.
AB  - We reported the development and psychometric evaluation of a Swedish 14-item and
      a five-item short form of the Oral Health Impact Profile. The 14-item version was
      derived from the English-language short form developed by Slade in1997. The five
      item version was derived from the German-language short form developed by John et
      al. in 2006. Validity, reliability and normative values for the two short form
      summary scores were determined in a random sample of the adult Swedish population
      (response rate: 46%, N = 1366 subjects). Subjects with sufficient OHRQoL
      information to calculate a summary score (N = 1309) were on average 50.1 +/- 17.4
      years old, and 54% were women. Short form summary scores correlated highly with
      the 49-item OHIP-S (r >= 0.97 for OHIP-S14, r >= 0.92 for OHIP-S5) and with self
      report of oral health (r >= 0.41). Reliability, measured with Cronbach's alpha
      (0.91 for OHIP-S14, 0.77 for OHIP-S5), was sufficient. In the general population,
      50% of the subjects had >=2 OHIP-S14 score points and 10% had >=11 points,
      respectively. Among subjects with their own teeth only and/or fixed dental
      prostheses and with partial removable dental prostheses, 50% of the population
      had >=2 OHIP-S14 score points, and 10% had >=11 points. For subjects with
      complete dentures, the corresponding figures were 3 and 24 points. OHIP-S5
      medians for subjects in the three population groups were 1, 1 and 2 points.
      Swedish 14-item and 5-item short forms of the OHIP have sufficient psychometric
      properties and provide a detailed overview about impaired OHRQoL in Sweden. The
      norms will serve as reference values for future studies.

PMID- 24447241
TI  - A homochiral metal-organic framework as an effective asymmetric catalyst for
      cyanohydrin synthesis.
AB  - A homochiral metal-organic framework (MOF) of an enantiopure 2,2'-dihydroxy-1,1'
      biphenyl ligand was constructed. After exchanging one proton of the dihydroxyl
      group for Li(I) ions, the framework is shown to be a highly efficient and
      recyclable heterogeneous catalyst for asymmetric cyanation of aldehydes with up
      to >99% ee. Compared with the homogeneous counterpart, the MOF catalyst exhibits
      significantly enhanced catalytic activity and enantioselectivity, especially at a
      low catalyst/substrate ratio, due to that the rigid framework could stabilize the
      catalytically active monolithium salt of biphenol against its free transformation
      to catalytically inactive and/or less active assemblies in reactions. The
      synthetic utility of the cyanation was demonstrated in the synthesis of (S)
      bufuralol (a nonselective beta-adrenoceptor blocking agent) with 98% ee. 

PMID- 24447238
TI  - Homocysteine levels and treatment effect in the PROspective Study of Pravastatin
      in the Elderly at Risk.
AB  - OBJECTIVES: To assess the effect of preventive pravastatin treatment on coronary
      heart disease (CHD) morbidity and mortality in older persons at risk for
      cardiovascular disease (CVD), stratified according to plasma levels of
      homocysteine. DESIGN: A post hoc subanalysis in the PROspective Study of
      Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double
      blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.
      SETTING: Primary care setting in two of the three PROSPER study sites
      (Netherlands and Scotland). PARTICIPANTS: Individuals (n = 3,522, aged 70-82,
      1,765 male) with a history of or risk factors for CVD were ranked in three groups
      depending on baseline homocysteine level, sex, and study site. INTERVENTION:
      Pravastatin (40 mg) versus placebo. MEASUREMENTS: Fatal and nonfatal CHD and
      mortality. RESULTS: In the placebo group, participants with a high homocysteine
      level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2-2.5, P
      = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n =
      597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin
      treatment was 1.6% (95% CI = -1.6 to 4.7%) in the low homocysteine group and 6.7%
      (95% CI = 2.7-10.7%) in the high homocysteine group (difference 5.2%, 95% CI =
      0.11-10.3, P = .046). Therefore, the number needed to treat (NNT) with
      pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events
      was 14.8 (95% CI = 9.3-36.6) for high homocysteine and 64.5 (95% CI = 21.4
      infinity) for low homocysteine. CONCLUSION: In older persons at risk of CVD,
      those with high homocysteine are at highest risk for fatal and nonfatal CHD. With
      pravastatin treatment, this group has the highest absolute risk reduction and the
      lowest NNT to prevent fatal and nonfatal CHD.

PMID- 24447242
TI  - Lobe-specific calmodulin binding to different ryanodine receptor isoforms.
AB  - Ryanodine receptors (RyRs) are large ion channels that are responsible for the
      release of Ca(2+) from the sarcoplasmic/endoplasmic reticulum. Calmodulin (CaM)
      is a Ca(2+) binding protein that can affect the channel open probability at both
      high and low Ca(2+) concentrations, shifting the Ca(2+) dependencies of channel
      opening in an isoform-specific manner. Here we analyze the binding of CaM and its
      individual domains to three different RyR regions using isothermal titration
      calorimetry. We compared binding to skeletal muscle (RyR1) and cardiac (RyR2)
      isoforms, under both Ca(2+)-loaded and Ca(2+)-free conditions. CaM can bind all
      three regions in both isoforms, but the binding modes differ appreciably in two
      segments. The results highlight a Ca(2+)/CaM and apoCaM binding site in the C
      terminal fifth of the channel. This binding site is the target for malignant
      hyperthermia and central core disease mutations in RyR1, which affect the
      energetics and mode of CaM binding. 

PMID- 24447243
TI  - Resolving biodegradation patterns of persistent saturated hydrocarbons in
      weathered oil samples from the Deepwater Horizon disaster.
AB  - Biodegradation plays a major role in the natural attenuation of oil spills.
      However, limited information is available about biodegradation of different
      saturated hydrocarbon classes in surface environments, despite that oils are
      composed mostly of saturates, due to the limited ability of conventional gas
      chromatography (GC) to resolve this compound group. We studied eight weathered
      oil samples collected from four Gulf of Mexico beaches 12-19 months after the
      Deepwater Horizon disaster. Using comprehensive two-dimensional gas
      chromatography (GC * GC), we successfully separated, identified, and quantified
      several distinct saturates classes in these samples. We find that saturated
      hydrocarbons eluting after n-C22 dominate the GC-amenable fraction of these
      weathered samples. This compound group represented 8-10%, or 38-68 thousand
      metric tons, of the oil originally released from Macondo well. Saturates in the n
      C22 to n-C29 elution range were found to be partly biodegraded, but to different
      relative extents, with ease of biodegradation decreasing in the following order:
      n-alkanes > methylalkanes and alkylcyclopentanes+alkylcyclohexanes > cyclic and
      acyclic isoprenoids. We developed a new quantitative index designed to
      characterize biodegradation of >n-C22 saturates. These results shed new light
      onto the environmental fate of these persistent, hydrophobic, and mostly
      overlooked compounds in the unresolved complex mixtures (UCM) of weathered oils.

PMID- 24447245
TI  - Evaluation of the migration of 15 photo-initiators from cardboard packaging into
      Tenax((r)) using ultra-performance liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS).
AB  - Photo-initiators are widely used to cure ink on packaging materials used in food
      applications such as plastic films or cartonboards. In migration studies, food
      simulants are very often used to simulate food, like Tenax((r)), which is the
      simulant for dry foodstuffs. In this paper a fast and reliable confirmation
      method for the determination of the following photo-initiators in Tenax((r)) is
      described: benzophenone (BP), 4,4'-bis(diethylamino)benzophenone (DEAB), 2-chloro
      9H-thioxanthen-9-one (CTX), 1-chloro-4-propoxy-9H-thioxanthen-9-one (CPTX), 2,4
      diethyl-9H-thioxanthen-9-one (DETX), 2,2-dimethoxy-2-phenyl acetophenone (DMPA),
      4-(dimethylamino)benzophenone (DMBP), 2-ethylanthraquinone (EA), ethyl-4
      dimethylaminobenzoate (EDMAB), 1-hydroxylcyclohexyl phenyl ketone (HCPK), 2
      hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (HMMP), 2-isopropyl-9H
      thioxanthen-9-one (ITX), 4-methylbenzophenone (MBP), Michler's ketone (MK), and 4
      phenylbenzophenone (PBZ). After the migration study was completed, the simulant
      Tenax((r)) was extracted using acetonitrile, followed by analysis on ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
      Quantification was carried out using benzophenone-d10 (BP-d10) as internal
      standard. The presented method is validated in terms of matrix effect,
      specificity, linearity, recovery, precision and sensitivity, showing the method
      can detect all photo-initiators at very low concentrations (LOD < 0.125 ug g(-1)
      for all substances). Finally, the procedure was applied to real samples, proving
      the capabilities of the presented method.

PMID- 24447246
TI  - Analysis of localized diabatic states beyond the condon approximation for
      excitation energy transfer processes.
AB  - In a previous paper [ Fatehi , S. ; et al. J. Chem. Phys. 2013 , 139 , 124112 ],
      we demonstrated a practical method by which analytic derivative couplings of Boys
      localized CIS states can be obtained. In this paper, we now apply that same
      method to the analysis of triplet-triplet energy transfer systems studied by
      Closs and collaborators [ Closs , G. L. ; et al. J. Am. Chem. Soc. 1988 , 110 ,
      2652 ]. For the systems examined, we are able to conclude that (i) the derivative
      coupling in the BoysOV basis is negligible, and (ii) the diabatic coupling will
      likely change little over the configuration space explored at room temperature.
      Furthermore, we propose and evaluate an approximation that allows for the
      inexpensive calculation of accurate diabatic energy gradients, called the
      "strictly diabatic" approximation. This work highlights the effectiveness of
      diabatic state analytic gradient theory in realistic systems and demonstrates
      that localized diabatic states can serve as an acceptable approximation to
      strictly diabatic states. 

PMID- 24447247
TI  - Natural extracts stimulate membrane-associated mechanisms of resistance in Gram
      negative bacteria.
AB  - Several mechanisms are involved in the bacterial resistance towards antimicrobial
      agents. The membrane-associated mechanisms of resistance were studied in
      Escherichia coli strains after incubation with Thymus maroccanus essential oil,
      its major components (carvacrol and thymol) or with certain antibiotics. The
      minimum inhibitory concentration (MIC) and the expression of membrane proteins,
      porins and efflux pumps were determined in wild type and derivative strains.
      Derivative strains adapted to different compounds displayed a high level of
      resistance to all tested antibiotics. The MIC increase is associated with an
      overexpression of an efflux pump immunorelated to AcrAB-TolC in various variants.
      Interestingly, the expression of outer membrane proteins slightly decreases in
      these strains. We demonstrate that the increase in antibiotic resistance
      correlates with membrane changes observed in the variants. This type of bacterial
      adaptation to natural compounds can occur in vivo providing the
      emergence/selection of bacteria less susceptible to clinically used antibiotics.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Thymus maroccanus essential oil and some
      major components are able to select variants that modify the expression of
      transporters involved in the influx (porins) and in the efflux (AcrAB family) of
      various drugs. Importantly, these membrane proteins are involved in the transport
      of natural compounds and several antibiotic families. This special 'membrane
      adaptation' can explain the persistence of less susceptible/tolerant bacteria in
      the environment where natural compounds are present and the continuous
      stimulation of efflux systems in these bacteria.

PMID- 24447248
TI  - Structure-based optimization of tyrosine kinase inhibitor CLM3. Design,
      synthesis, functional evaluation, and molecular modeling studies.
AB  - Recent advances in the knowledge of thyroid carcinomas development identified
      receptor tyrosine kinases, like VEGFR2 and RET, as viable and promising targets.
      Accordingly, their inhibition is emerging as the major therapeutic strategy to
      treat these pathologies. In this study we describe the synthesis and the
      functional evaluation of three different series of 4-substituted pyrazolo[3,4
      d]pyrimidine derivatives, 8a-g, 9a-g, and 10a-g, designed exploiting a structure
      based optimization of the previously developed inhibitor CLM3. Compared to the
      lead, the novel compounds markedly improved both their inhibitory profile against
      the target proteins, VEGFR2 and RET, and their antiproliferative efficacy against
      the medullary thyroid cancer cell line TT. Significantly, compounds 8b, 9c, and
      10c proved to block the kinase activity of the mutant RET(V804L), which still
      lacks effective inhibitors. 

PMID- 24447250
TI  - Ventilator-associated pneumonia due to carbapenem-resistant Gram-negative bacilli
      in an intensive care unit without carbapenemase-producing Enterobacteriaceae or
      epidemic Acinetobacter baumannii.
AB  - Risk factors for ventilator-associated pneumonia (VAP) caused by carbapenem
      resistant Gram-negative bacilli (CR-GNB) have rarely been evaluated in intensive
      care units (ICU) without epidemic carbapenemase-producing Acinetobacter baumannii
      or Enterobacteriaceae. We addressed this issue in a cohort of 141 patients
      (previous antimicrobial exposure, n = 131) with a first episode of VAP in a
      medico-surgical ICU. Twenty-six VAP (18.4%) involved a CR-GNB (Pseudomonas
      aeruginosa, n = 14, Stenotrophomonas maltophilia, n = 11, and A. baumannii, n =
      1), without previous carbapenem exposure in 12 (46.1%) cases. GNB resistant to
      all beta-lactams except carbapenems were equally isolated in CR-GNB VAP (co
      infections, 23%) and other episodes (30%). Previous exposure to aminoglycosides
      (odds ratio (OR) 1.14 per day, 95% confidence interval (CI) 1.02-1.30, p = 0.02)
      and the number of antimicrobial classes used before VAP (OR 1.38 per class, 95%
      CI 1.10-1.73, p = 0.006) were the only independent predictors of CR-GNB. These
      results suggest that the empirical use of a carbapenem-colistin combination
      should be evaluated in late-onset VAP following broad-spectrum antimicrobial
      exposure.

PMID- 24447251
TI  - Development of macrolide resistance in Mycoplasma pneumoniae-infected Swedish
      patients treated with macrolides.
AB  - BACKGROUND: The proportion of Mycoplasma pneumoniae isolates carrying point
      mutations in the 23S region of the genome associated with macrolide resistance
      has increased. We evaluated the probability of developing M. pneumoniae macrolide
      resistance mutations during macrolide treatment. METHODS: M. pneumoniae strains
      from initial and follow-up oropharyngeal samples from 38 Swedish patients were
      tested for 23S rRNA mutations by amplifying and pyrosequencing the gene target
      region. The duration of symptoms and of M. pneumoniae carriage were recorded in
      cases with and without the macrolide resistance mutation. RESULTS: Macrolide
      resistance mutations were absent in all baseline strains. Twenty-two patients
      were prescribed macrolides; the longest M. pneumoniae carriage time in these
      patients was 7 months and the longest symptomatic period was 7.5 months.
      Macrolide resistance was detected after macrolide treatment in 1 patient
      (carriage time 3.5 months and symptomatic period 7.5 months). CONCLUSIONS: M.
      pneumoniae may develop macrolide resistance during macrolide treatment. A long
      duration of M. pneumoniae carriage and symptoms is common in patients regardless
      of the presence of resistance.

PMID- 24447252
TI  - In vitro activity of rifampicin alone and in combination with imipenem against
      multidrug-resistant Acinetobacter baumannii harboring the blaOXA-72 resistance
      gene.
AB  - BACKGROUND: The growing incidence of multidrug resistance (MDR) in bacteria is an
      emerging challenge in the treatment of infections. Acinetobacter baumannii is an
      opportunistic pathogen prone to exhibit MDR that contributes significantly to
      nosocomial infections, particularly in severely ill patients. Thus, we performed
      research on rifampicin activity against selected MDR OXA-72 carbapenemase
      producing A. baumannii strains. Since it is widely accepted that rifampicin
      should not be used as monotherapy in order to avoid the rapid development of
      rifampicin resistance, we evaluated the efficacy of combination therapy with
      imipenem. METHODS: Minimal inhibitory concentrations (MICs) of both rifampicin
      and imipenem were determined by use of the broth microdilution method.
      Evaluations of the interactions between rifampicin and imipenem were performed by
      analysis of the fractional inhibitory concentration index (?FIC), determined
      using the checkerboard titration method. RESULTS: All tested isolates showed full
      susceptibility to rifampicin. The checkerboard method revealed synergism in 5
      isolates (29%) and an additive effect in another 5 isolates (29%); no difference
      was reported in the remaining 7 isolates (41%). Strains moderately resistant to
      imipenem (MIC <= 64 mg/l) tended to show synergy or additive interaction.
      CONCLUSIONS: We conclude that in vitro synergism or an additive interaction
      between rifampicin and imipenem most likely occurs in A. baumannii strains
      showing moderate resistance to imipenem (MIC <= 64 mg/l). Moreover, utilizing
      this combination in the therapy of infections caused by strains exhibiting higher
      levels of resistance (MIC > 64 mg/l) is not recommended since in this setting
      imipenem could not prevent the development of rifampicin resistance.

PMID- 24447253
TI  - Detection of specific IgG antibodies in blood donors and tick-borne encephalitis
      virus in ticks within a non-endemic area in southeast Norway.
AB  - BACKGROUND: Tick-borne encephalitis (TBE) is an emerging tick-borne disease in
      Europe. In Norway, the first TBE case occurred in 1997, and since then 1-14 cases
      have been detected annually along the southern coast. No TBE cases have yet been
      notified from the eastern coastal area. This study was conducted to assess the
      need for diagnostic tests and vaccine recommendation for this part of Norway.
      METHODS: Four hundred and sixty-one blood donors living in the county of Ostfold
      were enrolled. After informed consent was obtained, the participants submitted a
      blood sample and filled out a questionnaire regarding tick bites, outdoor
      activities, and Flavivirus vaccines and diseases. Ixodes ricinus ticks were
      collected from the immediate vicinity and were examined in pools of 10 for TBE
      virus. RESULTS: Eight human samples were TBE virus IgG-positive by ELISA and 5 of
      these samples were confirmed positive by neutralization test. Excluding the 2
      samples from participants who had reported previous TBE vaccination, this shows a
      seroprevalence among blood donors of 0.65%. The existence of TBEV in the region
      was verified in nymphs of Ixodes ricinus by a prevalence of 0.14%. CONCLUSIONS:
      The seroprevalence of TBE virus IgG and the TBE virus detected in ticks, indicate
      that TBE cases could occasionally occur in the area. The results should be made
      available to health care personnel to raise awareness for preventative measures.

PMID- 24447254
TI  - Vascular calcification in long-term kidney transplantation.
AB  - AIM: Vascular calcification (VC) is common among patients with chronic kidney
      disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk
      factors such as diabetes mellitus (DM), hypertension and phosphate retention.
      Kidney transplantation improves kidney function and abnormal mineral metabolism
      at the same time. It remains unclear whether kidney transplantation favourably
      impacts VC in the long-term. METHODS: The present study examined VC in 132 kidney
      transplant (KT) recipients who had been transplanted for longer than one year.
      The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney
      transplant (KT) waiting list. RESULTS: The median KT vintage was 88 months. The
      prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P
      = 0.2). There were no differences in age, gender, body mass index (BMI), the
      prevalence of DM or CVD between the two groups. Among patients with
      calcification, a more severe degree was observed in KT recipients (P = 0.01).
      Aging, DM, CVD and dialysis vintage were associated with significant VC in both
      groups. The degree of VC in KT recipients was more pronounced than that in CKD
      patients among those who experienced prolonged dialysis vintage (>2 years) (P =
      0.04). Among KT recipients, the severity of VC increased with the length of time
      after transplantation and became more substantial after 5 years. CONCLUSIONS:
      Long-term KT recipients demonstrated a more severe degree of VC compared to
      matched CKD stages 5-5D patients. The severity of VC became more pronounced among
      those with longer transplant vintage and was in part influenced by past dialysis
      experience.

PMID- 24447255
TI  - Which type of atrophic acne scar (ice-pick, boxcar, or rolling) responds to
      nonablative fractional laser therapy?
AB  - BACKGROUND: Few studies have examined the role of fractional lasers in individual
      acne scars (ice-pick, box car, rolling) using objective assessment tools in
      darkly pigmented skin. OBJECTIVE: To evaluate the effect of 1,540-nm fractional
      lasers on individual acne scars. METHODS AND MATERIALS: A prospective
      interventional study was conducted in 35 patients using a 1,540-nm fractional
      laser. Six sessions were performed with four passes per session and a dose
      varying from 70 to 100 mJ to maximize the DWR. A self-devised objective
      assessment tool with dose settings to optimize the depth-to-width ratio (DWR) and
      a visual analog scale (VAS) were used to count individual atrophic scars. Final
      results were assessed 6 months after final laser treatment. RESULTS: Acne scar
      reduction efficiency was used to validate the improvement of individual scars, a
      meaningful difference was considered as 51% or greater improvement. The boxcar
      scars (52.9%) responded better than the rolling (43.1%) and ice-pick scars
      (25.9%), with statistically significant improvement (p < .05) seen in boxcar
      scars after four sessions. Overall VAS scores revealed significant improvement (p
      < .001). CONCLUSION: Using an objective evaluation tool, an erbium-doped glass
      laser was found to improve atrophic acne scars, markedly so for boxcar and
      rolling scars. The VAS score overestimated improvement because of its subjective
      nature.

PMID- 24447256
TI  - A new species of Ituglanis representing the southernmost record of the genus,
      with comments on phylogenetic relationships (Teleostei: Siluriformes:
      Trichomycteridae).
AB  - Ituglanis australis new species, is described from tributaries of the Laguna dos
      Patos and Rio Uruguay, in Brazil and Uruguay. This represents the southernmost
      record of the genus and the first occurrence of a species of Ituglanis in those
      systems. It is distinguished from all its congeners, except Ituglanis parahybae
      and Ituglanis cahyensis, by its body pigmentation with three well-defined dark
      brown stripes running along each flank. Ituglanis australis differs from I.
      parahybae and I. cahyensis in the pectoral- and pelvic-fin ray counts, the
      pattern of the cephalic laterosensory system and the number of dorsal-fin basal
      radials. The new species, as well as several other examined congeners, has the
      levator internus IV muscle attached to the dorsal face of the posttemporo
      supracleithrum; a condition that corroborates the inclusion of Ituglanis into a
      large trichomycterine clade that also includes Bullockia, Hatcheria, Scleronema
      and several species of Trichomycterus. Previous proposals of the affinities
      within Ituglanis are reviewed and, despite some advances, the phylogenetic
      relationships among species of the genus remain largely unknown. 

PMID- 24447257
TI  - Magnetic-field-induced orientational phase structure transition.
AB  - Magnetic field effect on the phase transition at high temperature (from 50 
      degrees C) inside the magnetic field has been found in C14G2 (N
      tetradecyllactobionamide)/C12EO4 (tetraethylene glycol monododecyl ether)/D2O
      system. The phase was transited quickly from lamellar phase to isotropic phases
      [bottom, micellar phase (L1 phase) and top, sponge phase (L3 phase)] induced by a
      magnetic field, which was demonstrated by (2)H NMR and FF-TEM measurements. The
      isotropic phases induced by magnetic field were not stable, and the upper L3
      phase can recover to lamellar phase after being restored in a 55  degrees C
      thermostat outside the magnetic field for about one month. During the mechanism
      study, the C12EO4 molecule was proved to be the dominant component for the phase
      transition induced by the magnetic field, while the C14G2 molecule was the
      auxiliary and just affected the transition speed. The breaking and rebuilding of
      hydrogen bonds could play an important role in the phase transition and
      recovering. Moreover, the surfactant concentration had an effect on the speed of
      phase transiting and phase recovering. These observations could provide an
      understanding of the phase transition and also the applications for the
      controlled drug delivery system of bilayer membranes driving, induced by the
      magnetic field. 

PMID- 24447258
TI  - Enamel wear caused by monolithic zirconia crowns after 6 months of clinical use.
AB  - The purpose of this study was to evaluate enamel wear caused by monolithic
      zirconia crowns and to compare this with enamel wear caused by contralateral
      natural antagonists. Twenty monolithic zirconia crowns were placed in 20 patients
      requiring full molar crowns. For measurement of wear, impressions of both jaws
      were made at baseline after crown cementation and at 6-month follow-up. Mean and
      maximum wear of the occlusal contact areas of the crowns, of their natural
      antagonists and of the two contralateral natural antagonists were measured by the
      use of plaster replicas and 3D laser scanning methods. Wear differences were
      investigated by the use of two-sided paired Student's t-tests and by linear
      regression analysis. Mean vertical loss (maximum vertical loss in parentheses)
      was 10 (43) MUm for the zirconia crowns, 33 (112) MUm for the opposing enamel, 10
      (58) MUm for the contralateral teeth and 10 (46) MUm for the contralateral
      antagonists. Both mean and maximum enamel wear were significantly different
      between the antagonists of the zirconia crowns and the contralateral antagonists.
      Gender and activity of the masseter muscle at night (bruxism) were identified as
      possible confounders which significantly affected wear. Under clinical
      conditions, monolithic zirconia crowns seem to be associated with more wear of
      opposed enamel than are natural teeth. With regard to wear behaviour, clinical
      application of monolithic zirconia crowns is justifiable because the amount of
      antagonistic enamel wear after 6 months is comparable with, or even lower than,
      that caused by other ceramic materials in previous studies. 

PMID- 24447259
TI  - In vitro and in vivo models of colorectal cancer: antigenotoxic activity of
      berries.
AB  - The etiology of colorectal cancer (CRC), a common cause of cancer-related
      mortality globally, has strong associations with diet. There is considerable
      epidemiological evidence that fruits and vegetables are associated with reduced
      risk of CRC. This paper reviews the extensive evidence, both from in vitro
      studies and animal models, that components of berry fruits can modulate
      biomarkers of DNA damage and that these effects may be potentially
      chemoprotective, given the likely role that oxidative damage plays in mutation
      rate and cancer risk. Human intervention trials with berries are generally
      consistent in indicating a capacity to significantly decrease oxidative damage to
      DNA, but represent limited evidence for anticarcinogenicity, relying as they do
      on surrogate risk markers. To understand the effects of berry consumption on
      colorectal cancer risk, future studies will need to be well controlled, with
      defined berry extracts, using suitable and clinically relevant end points and
      considering the importance of the gut microbiota. 

PMID- 24447260
TI  - IR, Raman, and NMR studies of the short-range structures of 0.5Na2S + 0.5[xGeS2 +
      (1-x)PS(5/2)] mixed glass-former glasses.
AB  - A nonlinear and nonadditive composition-dependent change of the ionic
      conductivity in mixed glass-former (MGF) glasses when one glass former, such as
      PS(5/2), is replaced by a second glass former, such as GeS2, at constant alkali
      modifier concentrations, such as Na2S, is known as the mixed glass-former effect
      (MGFE). Alkali ion conducting glasses are of particular interest for use as solid
      electrolytes in alkali-based all-solid-state batteries because sulfide amorphous
      materials have significantly higher alkali ion conductivities than their oxide
      glass counterparts. In this study of the ternary MGF system Na2S + GeS2 +
      PS(5/2), we report the careful structural characterization of these glasses using
      a combination of vibrational, infrared (IR), Raman, and nuclear magnetic
      resonance (NMR) spectroscopies. Our measurements of the 0.5Na2S + 0.5[xGeS2 + (1
      x)PS(5/2)] MGF system show that this glass system exhibits a strongly negative
      MGFE and non-Arrhenius ionic conductivities. While this negative MGFE in the
      Na(+) ion conductivity makes these glasses less attractive for use in solid-state
      Na batteries, the structural origin of this effect is important to better
      understand the mechanisms of ion conduction in the glassy state. For these
      reasons, we have examined the structures of ternary 0.5Na2S + 0.5[xGeS2 + (1
      x)PS(5/2)] glasses using Raman, IR, and (31)P MAS NMR spectroscopies. In these
      studies, it is found that the substitution of PS(5/2) by GeS2, that is,
      increasing x, leads to unequal sharing of the Na(+) in these glasses. Thus, in
      all MGF compositions, phosphorus groups are associated with a disproportionately
      larger fraction, f(Na(P)) > 0.5(1 - x), of the Na(+) ions while the germanium
      groups are found to be Na(+)-deficient relative to the total amount of Na(+)
      present in the glass, that is, f(Na(Ge)) < 0.5x. From the spectroscopic study of
      these glasses, a short-range order (SRO) structural model is developed for these
      glasses and is based on the germanium and phosphorus SRO groups in these glasses
      as a first step in understanding the unique negative MGFE and non-Arrhenius
      behavior in the Na(+) ion conductivity in these glasses.

PMID- 24447261
TI  - Endoscopic resection yields reliable outcomes for small rectal neuroendocrine
      tumors.
AB  - BACKGROUND AND AIM: We analyzed the characteristics of gastrointestinal
      neuroendocrine tumors and examined the outcomes and safety of modalities in
      rectal neuroendocrine tumors. METHODS: Between 2007 and 2011, a total of 91
      patients with gastrointestinal neuroendocrine tumors were retrospectively
      reviewed in terms of the characteristics of tumors. RESULTS: Sixty-six patients
      had rectal neuroendocrine tumors and underwent endoscopic mucosal resection (EMR,
      n = 29), endoscopic submucosal dissection (ESD, n = 23), or transanal endoscopic
      microsurgery (TEM, n = 14). The complete resection rate was higher in the ESD
      group (82.7%) and in the TEM group (100%) compared to the EMR group (65.5%) (P <
      0.046). The complication rate was higher in the ESD group (47.8%) than in the EMR
      group (18.5%) (P = 0.003). No local tumor recurrence was observed in all
      patients, regardless of the procedure, during the median follow-up period of 21.5
      +/- 13.5 months. CONCLUSIONS: ESD achieved a higher complete resection rate than
      EMR and comparable to TEM. Tumor recurrence was not observed in the endoscopic
      resection and TEM groups, regardless of the completeness of resection. Small
      neuroendocrine tumors of the gastrointestinal tract can be managed reliably with
      both endoscopic resection and TEM.

PMID- 24447262
TI  - Left ventricular rupture after embolic myocardial infarction due to mitral valve
      endocarditis.
AB  - We report a very rare case of a 43-year-old patient with fatal left ventricular
      subepicardial aneurysm rupture complicating embolic myocardial infarction due to
      mitral valve infective endocarditis. 

PMID- 24447263
TI  - Predicting muscle mass from anthropometry using magnetic resonance imaging as
      reference: a systematic review.
AB  - Identification and management of sarcopenia are limited by lack of reliable
      simple approaches to assess muscle mass. The aim of this review is to identify
      and evaluate simple methods to quantify muscle mass/volume of adults. Using
      Cochrane Review methodology, Medline (1946-2012), Embase (1974-2012), Web of
      Science (1898-2012), PubMed, and the Cochrane Library (to 08/2012) were searched
      for publications that included prediction equations (from anthropometric
      measurements) to estimate muscle mass by magnetic resonance imaging (MRI) in
      adults. Of 257 papers identified from primary search terms, 12 studies met the
      inclusion criteria. Most studies (n = 10) assessed only regional/limb muscle
      mass/volume. Many studies (n = 9) assessed limb circumference adjusted for
      skinfold thickness, which limits their practical applications. Only two included
      validation in separate subject-samples, and two reported relationships between
      whole-body MRI-measured muscle mass and anthropometry beyond linear correlations.
      In conclusion, one simple prediction equation shows promise, but it has not been
      validated in a separate population with different investigators. Furthermore, it
      did not incorporate widely available trunk/limb girths, which have offered
      valuable prediction of body composition in other studies. 

PMID- 24447264
TI  - Self-assembly of octapod-shaped colloidal nanocrystals into a hexagonal ballerina
      network embedded in a thin polymer film.
AB  - Nanoparticles with unconventional shapes may exhibit different types of assembly
      architectures that depend critically on the environmental conditions under which
      they are formed. Here, we demonstrate how the presence of polymer (polymethyl
      methacrylate, PMMA) molecules in a solution, in which CdSe(core)/CdS(pods)
      octapods are initially dispersed, affects the octapod-polymer organization upon
      solvent evaporation. We show that a fast drop-drying process can induce a
      remarkable two-dimensional (2D) self-assembly of octapods at the polymer/air
      interface. In the resulting structure, each octapod is oriented like a
      "ballerina", that is, only one pod sticks out of the polymer film and is
      perpendicular to the polymer-air interface, while the opposite pod (with respect
      to the octapod's center) is fully immersed in the film and points toward the
      substrate, like a ballerina performing a grand battement. In some areas, a
      hexagonal-like pattern is formed by the ballerinas in which the six nonvertical
      pods, which are all embedded in the film, maintain a pod-pod parallel
      configuration with respect to neighboring particles. We hypothesize that the
      mechanism responsible for such a self-assembly is based on a fast adsorption of
      the octapods from bulk solution to the droplet/air interface during the early
      stages of solvent evaporation. At this interface, the octapods maintain enough
      rotational freedom to organize mutually in a pod-pod parallel configuration
      between neighboring octapods. As the solvent evaporates, the octapods form a
      ballerina-rich octapod-polymer composite in which the octapods are in close
      contact with the substrate. Finally, we found that the resulting octapod-polymer
      composite is less hydrophilic than the polymer-only film. 

PMID- 24447265
TI  - Structure of human PIR1, an atypical dual-specificity phosphatase.
AB  - PIR1 is an atypical dual-specificity phosphatase (DSP) that dephosphorylates RNA
      with a higher specificity than phosphoproteins. Here we report the atomic
      structure of a catalytically inactive mutant (C152S) of the human PIR1
      phosphatase core (PIR1-core, residues 29-205), refined at 1.20 A resolution. PIR1
      core shares structural similarities with DSPs related to Vaccinia virus VH1 and
      with RNA 5'-phosphatases such as the baculovirus RNA triphosphatase and the human
      mRNA capping enzyme. The PIR1 active site cleft is wider and deeper than that of
      VH1 and contains two bound ions: a phosphate trapped above the catalytic cysteine
      C152 exemplifies the binding mode expected for the gamma-phosphate of RNA, and ~6
      A away, a chloride ion coordinates the general base R158. Two residues in the
      PIR1 phosphate-binding loop (P-loop), a histidine (H154) downstream of C152 and
      an asparagine (N157) preceding R158, make close contacts with the active site
      phosphate, and their nonaliphatic side chains are essential for phosphatase
      activity in vitro. These residues are conserved in all RNA 5'-phosphatases that,
      analogous to PIR1, lack a "general acid" residue. Thus, a deep active site
      crevice, two active site ions, and conserved P-loop residues stabilizing the
      gamma-phosphate of RNA are defining features of atypical DSPs that specialize in
      dephosphorylating 5'-RNA. 

PMID- 24447266
TI  - Effects of ropivacaine concentration on the spread of sensory block produced by
      continuous thoracic paravertebral block: a prospective, randomised, controlled,
      double-blind study.
AB  - Factors affecting the distribution of continuous thoracic paravertebral block
      have never been examined. We designed this prospective, double-blind study to
      check whether continuous thoracic paravertebral block with a higher ropivacaine
      concentration would provide a wider segmental sensory block spread. Sixty
      consecutive patients undergoing pulmonary lobectomy or segmentectomy were
      randomly allocated to receive continuous paravertebral infusion of either 0.2% or
      0.5% ropivacaine (6 ml.h(-1) ). The primary outcome was the number of
      anaesthetised dermatomes as determined by loss of cold sensation 24 h after
      surgery. Twenty-seven patients per group were included in the final analysis. The
      median (IQR [range]) number of anaesthetised dermatomes 24 h after surgery was 4
      (3-6 [1-9]) with ropivacaine 0.2% and 4 (3-6 [2-11]) with ropivacaine 0.5% (p =
      0.66). Contrary to our expectation, the segmental spread of sensory block
      produced by continuous thoracic paravertebral block does not depend on
      ropivacaine concentration. 

PMID- 24447267
TI  - Protective effects of melatonin and quercetin on experimental lung injury induced
      by carbon tetrachloride in rats.
AB  - INTRODUCTION: Exposure to carbon tetrachloride (CCl4), a well-known toxicant,
      causes tissue damage by inducing oxidative stress via formation of free radicals.
      The fundamental structure of the organs of rats and humans is similar, so
      administration of CCl4 to rats is an accepted experimental model to produce
      oxidative damage to various tissues including pulmonary tissue. In this study, we
      evaluated the protective capacity of melatonin and quercetin against CCl4-induced
      oxidative lung damage in rats. MATERIAL-METHODS: Rats were divided into five
      groups each containing seven rats as follows: Control group, Olive oil group CCl4
      group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were
      processed by routine histological and biochemical procedures. Sections were
      stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage
      score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and
      catalase (CAT) activities were assayed. RESULTS: The lung sections of control
      groups showed normal histological characteristics. Fibrosis, interstitial
      hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar
      edema, leukocyte, and macrophage infiltration were observed in lung sections of
      rats exposed to CCl4 alone. The findings were reduced in the treatments groups.
      The MDA level in the CCI4 group were significantly higher than in the other
      groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer
      groups were significantly higher than in the CCI4 group (p < .05). CONCLUSION: In
      conclusion, we suggest that agents with antioxidant properties such as melatonin
      and quercetin may have positive effects in the treatment of pulmonary diseases
      characterized by especially edema, inflammation, and fibrosis.

PMID- 24447268
TI  - Molecular logic gates on DNA origami nanostructures for microRNA diagnostics.
AB  - Molecular computing holds great promise for diagnosis and treatment of diseases
      at the molecular level; nevertheless, designing molecular logic gates to operate
      programmably and autonomously for molecular diagnostics still remains
      challenging. We designed logic gates on DNA Origami for microRNA analysis. As a
      demonstration, two indicators of heart failure, microRNA-21 and microRNA-195,
      were selected as the logic inputs. The logic gates contain two main modules:
      computation module and output module, performing in a single DNA Origami
      nanostructure. The computation module recognizes disease indicators, while the
      output module display different nanoscale symbols, "+" (positive) or "-"
      (negative), depending on the computing results. We demonstrated that the
      molecular logic gates worked well with single and two input combinations. 

PMID- 24447269
TI  - Effects of calcineurin inhibitors on paraoxonase and arylesterase activity after
      a kidney transplant.
AB  - OBJECTIVES: Cardiovascular disease is a common cause of morbidity and mortality
      in patients with chronic kidney failure, before and after a kidney transplant.
      Oxidation of lipoproteins that contain apolipoprotein B may contribute to the
      initiation of atherosclerosis. Paraoxonase may prevent cardiovascular disease. We
      compared the effects of different calcineurin inhibitors on risk factors for
      cardiovascular disease in kidney transplant recipients. MATERIALS AND METHODS: In
      16 kidney transplant recipients, treatment included tacrolimus in 8 patients and
      cyclosporine in 8 patients. Hemoglobin, glucose, renal function, lipid
      parameters, high-sensitivity C-reactive protein, homocysteine, malondialdehyde,
      paraoxonase activity, and arylesterase activity were measured before transplant
      and at 1, 6, and 12 months after the transplant. RESULTS: The levels of
      homocysteine and malondialdehyde did not change significantly in patients who
      received either tacrolimus or cyclosporine. The high-sensitivity C-reactive
      protein was decreased (tacrolimus group, 1 mo) and increased (cyclosporine group,
      6 and 12 mo) after the kidney transplant. Paraoxonase activity was increased
      (tacrolimus group, 1 mo). Arylesterase activity was increased (tacrolimus group,
      1, 6, and 12 mo; cyclosporine group, 1 and 6 mo). The percentage of change in
      arylesterase activity was higher at 12 months in the tacrolimus than in the
      cyclosporine group. CONCLUSIONS: Tacrolimus may be more effective than
      cyclosporine in improving risk factors for cardiovascular disease after kidney
      transplant.

PMID- 24447270
TI  - Hybridization at an ecotone: ecological and genetic barriers between three
      Iberian vipers.
AB  - The formation of stable genetic boundaries between emerging species is often
      diagnosed by reduced hybrid fitness relative to parental taxa. This reduced
      fitness can arise from endogenous and/or exogenous barriers to gene flow.
      Although detecting exogenous barriers in nature is difficult, we can estimate the
      role of ecological divergence in driving species boundaries by integrating
      molecular and ecological niche modelling tools. Here, we focus on a three-way
      secondary contact zone between three viper species (Vipera aspis, V. latastei and
      V. seoanei) to test for the contribution of ecological divergence to the
      development of reproductive barriers at several species traits (morphology,
      nuclear DNA and mitochondrial DNA). Both the nuclear and mitochondrial data show
      that all taxa are genetically distinct and that the sister species V. aspis and
      V. latastei hybridize frequently and backcross over several generations. We find
      that the three taxa have diverged ecologically and meet at a hybrid zone
      coincident with a steep ecotone between the Atlantic and Mediterranean
      biogeographical provinces. Integrating landscape and genetic approaches, we show
      that hybridization is spatially restricted to habitats that are suboptimal for
      parental taxa. Together, these results suggest that niche separation and
      adaptation to an ecological gradient confer an important barrier to gene flow
      among taxa that have not achieved complete reproductive isolation. 

PMID- 24447273
TI  - Psychometric goodness of the Mini Sleep Questionnaire.
AB  - AIM: The current study was conducted to evaluate the psychometric properties and
      analyze the convergent validity of the Italian version of the Mini Sleep
      Questionnaire (MSQ). In addition, it was aimed to put forward cut-off values to
      be used in screening protocols. METHODS: The MSQ was administered to 1830
      participants (age range 18-87 years), of whom 1208 also completed the Sleep
      Disorder Questionnaire (age range 18-87 years). A subgroup of 187 (age range 18
      71 years) participants was randomly chosen to test the test-retest reliability. A
      complete psychometric evaluation was performed on the MSQ. To study the validity
      of the tool, the Sleep Disorder Questionnaire was used as an external criterion
      to validate the MSQ. Using the Youden index, we calculated the cut-off values
      that performed best. Finally, we created receiver-operator curves to test the
      accuracy of each cut-off value identified. RESULTS: For the MSQ, Cronbach's alpha
      score was 0.77 while homogeneity was 0.26. Factorial analyses confirmed the
      presence of two dimensions: sleep (Cronbach's alpha 0.75; homogeneity 0.37) and
      wake (Cronbach's alpha 0.75; homogeneity 0.44). For each dimension, a cut-off
      value was identified (>16 and >14, respectively). Both cut-off values obtained an
      area under the curve higher than 0.80. CONCLUSIONS: Psychometric evaluation of
      the MSQ was satisfactory. The cut-off values analyzed in the present study showed
      good performance. On the whole, the results of this study suggest that the MSQ
      can be a useful screening tool.

PMID- 24447274
TI  - Prolonged morphometric study of barnacles grown on soft substrata of hydrogels
      and elastomers.
AB  - A long-term investigation of the shell shape and the basal morphology of
      barnacles grown on tough, double-network (DN) hydrogels and polydimethylsiloxane
      (PDMS) elastomer was conducted in a laboratory environment. The elastic modulus
      of these soft substrata varied between 0.01 and 0.47 MPa. Polystyrene (PS)
      (elastic modulus, 3 GPa) was used as a hard substratum control. It was found that
      the shell shape and the basal plate morphology of barnacles were different on the
      rigid PS substratum compared to the soft substrata of PDMS and DN hydrogels.
      Barnacles on the PS substratum had a truncated cone shape with a flat basal plate
      while on soft PDMS and DN gels, barnacles had a pseudo-cylindrical shape and
      their basal plates showed curvature. In addition, a large adhesive layer was
      observed under barnacles on PDMS, but not on DN gels. The effect of substratum
      stiffness is discussed in terms of barnacle muscle contraction, whereby the
      relative stiffness of the substratum compared to that of the muscle is considered
      as the key parameter. 

PMID- 24447275
TI  - Potent and selective double-headed thiophene-2-carboximidamide inhibitors of
      neuronal nitric oxide synthase for the treatment of melanoma.
AB  - Selective inhibitors of neuronal nitric oxide synthase (nNOS) are regarded as
      valuable and powerful agents with therapeutic potential for the treatment of
      chronic neurodegenerative pathologies and human melanoma. Here, we describe a
      novel hybrid strategy that combines the pharmacokinetically promising thiophene-2
      carboximidamide fragment and structural features of our previously reported
      potent and selective aminopyridine inhibitors. Two inhibitors, 13 and 14, show
      low nanomolar inhibitory potency (Ki = 5 nM for nNOS) and good isoform
      selectivities (nNOS over eNOS [440- and 540-fold, respectively] and over iNOS
      [260- and 340-fold, respectively]). The crystal structures of these nNOS
      inhibitor complexes reveal a new hot spot that explains the selectivity of 14 and
      why converting the secondary to tertiary amine leads to enhanced selectivity.
      More importantly, these compounds are the first highly potent and selective nNOS
      inhibitory agents that exhibit excellent in vitro efficacy in melanoma cell
      lines. 

PMID- 24447276
TI  - Peptides derived from phage display libraries as potential neutralizers of Shiga
      toxin-induced cytotoxicity in vitro and in vivo.
AB  - AIMS: To use the phage display technique to develop peptides with the capability
      to neutralize the cytotoxicity induced by Stx1 and Stx2 toxins produced by Shiga
      toxin-producing Escherichia coli (STEC). METHODS AND RESULTS: The phage display
      technique permitted the development of three peptides, named PC7-12, P12-26 and
      PC7-30, which bind to the globotriaosylceramide (Gb3) receptor for Shiga toxins
      produced by STEC. Moreover, these peptides were capable of competing efficiently
      with the Shiga toxins for binding to Gb3. The peptides described herein partially
      inhibited the Stx-induced cytotoxicity of cell-free filtrates of STEC O157 : H7
      and purified Stx toxins in Vero cells. The inhibition of lethality induced by Stx
      toxins in mice indicated that peptide PC7-30 inhibited the lethality caused by
      Stx1 (2LD50) in mice. CONCLUSIONS: The phage display technique permitted the
      development of peptides that inhibited the cytotoxicity induced by Stx toxins in
      vitro. Peptide PC7-30 inhibited the lethality of Stx1 in vivo; this molecule
      would be a promising candidate for the development of therapeutic agents for STEC
      related diseases in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: The selection
      of Gb3, the common receptor for Stx1 and Stx2, may contribute to the development
      of efficient neutralizers for both toxins, and our approach would be an
      interesting alternative for the development of therapeutic molecules for the
      treatment of diseases caused by STEC strains.

PMID- 24447279
TI  - Press CRTT to measure aggressive behavior: the unstandardized use of the
      competitive reaction time task in aggression research.
AB  - The competitive reaction time task (CRTT) is the measure of aggressive behavior
      most commonly used in laboratory research. However, the test has been criticized
      for issues in standardization because there are many different test procedures
      and at least 13 variants to calculate a score for aggressive behavior. We
      compared the different published analyses of the CRTT using data from 3 different
      studies to scrutinize whether it would yield the same results. The comparisons
      revealed large differences in significance levels and effect sizes between
      analysis procedures, suggesting that the unstandardized use and analysis of the
      CRTT have substantial impacts on the results obtained, as well as their
      interpretations. Based on the outcome of our comparisons, we provide suggestions
      on how to address some of the issues associated with the CRTT, as well as a
      guideline for researchers studying aggressive behavior in the laboratory.

PMID- 24447283
TI  - Plasma levels of leptin in reproductive-aged women with mild depressive and
      anxious states.
AB  - AIMS: Recent studies suggest that leptin may have an effect on emotion and mood.
      Low levels of leptin in depression and anxiety have been reported in many animal
      models; however in humans, it has yet to be elucidated as to whether plasma
      leptin levels are low in similar states. Therefore, in this study we investigated
      how plasma leptin level and salivary stress markers of reproductive-aged women,
      who constitute the majority of patients with mild depression and anxiety in our
      clinic, are different from those of healthy women. METHODS: We compared the
      results of the Medical Outcome Study 36-Item Short-Form Health Survey, the Self
      rating Questionnaire for Depression, the State-Trait Anxiety Inventory, plasma
      leptin levels, and salivary stress markers in 29 depressive and anxious
      reproductive-aged female patients with those in 26 age- and body-mass-index
      matched healthy female volunteers. RESULTS: The Short-Form 36, Self-rating
      Questionnaire for Depression and State-Trait Anxiety Inventory scores in the
      patients were worse and their leptin levels were lower than those in the healthy
      volunteers. There were no significant differences in salivary stress markers,
      such as chromogranin A and cortisol, between the patients and healthy volunteers.
      CONCLUSION: This study suggests that leptin might play a pathophysiological role
      in reproductive-aged female patients for mild depression and anxiety.

PMID- 24447280
TI  - Development and validation of Triarchic construct scales from the psychopathic
      personality inventory.
AB  - The Triarchic model of psychopathy describes this complex condition in terms of
      distinct phenotypic components of boldness, meanness, and disinhibition. Brief
      self-report scales designed specifically to index these psychopathy facets have
      thus far demonstrated promising construct validity. The present study sought to
      develop and validate scales for assessing facets of the Triarchic model using
      items from a well-validated existing measure of psychopathy-the Psychopathic
      Personality Inventory (PPI). A consensus-rating approach was used to identify PPI
      items relevant to each Triarchic facet, and the convergent and discriminant
      validity of the resulting PPI-based Triarchic scales were evaluated in relation
      to multiple criterion variables (i.e., other psychopathy inventories, antisocial
      personality disorder features, personality traits, psychosocial functioning) in
      offender and nonoffender samples. The PPI-based Triarchic scales showed good
      internal consistency and related to criterion variables in ways consistent with
      predictions based on the Triarchic model. Findings are discussed in terms of
      implications for conceptualization and assessment of psychopathy.

PMID- 24447284
TI  - High sputum total adiponectin is associated with low odds for asthma.
AB  - OBJECTIVE: Adipose tissue produces adiponectin, an anti-inflammatory protein.
      High systemic total adiponectin is associated with a low risk for incident asthma
      but the association with lung adiponectin is not known. Our objective was to
      evaluate the association between sputum total adiponectin and asthma. METHODS:
      This case-control study included 44 cases with objectively-confirmed asthma and
      an equal number of body mass index (BMI) and sex-matched controls. Serum and
      sputum adiponectin were estimated by ELISA and Western Blot technique,
      respectively. While Fisher's exact test, t-test and Spearman's correlations were
      used for univariate analyses, Spearman and regression analyses were performed for
      multivariable analyses. RESULTS: While high-molecular-weight adiponectin was the
      dominant isoform in serum, medium-molecular-weight isoform was dominant in
      sputum. Sputum total adiponectin was not correlated with serum adiponectin or
      BMI. Sputum total adiponectin was lower among asthmatics than controls (p =
      0.03), although individual sputum isoforms were not similarly associated. High
      sputum total adiponectin was associated with lower odds for asthma (OR 0.33, 95%
      C.I. 0.12, 0.91), even after adjustment for systemic adiposity measures including
      serum adiponectin. CONCLUSIONS: High sputum total adiponectin predicted lower
      odds for asthma, even after adjustment for serum adiponectin. Although not
      studied, it is possible that pharmacological modulation of sputum adiponectin may
      suggest new ways to prevent and/or treat asthma.

PMID- 24447285
TI  - The Portuguese DISABKIDS Asthma Module: a global index of asthma-specific quality
      of life for children and adolescents.
AB  - BACKGROUND: The KIDSCREEN and DISABKIDS questionnaires constitute a modular
      system for assessing the health-related quality of life (HrQoL) of
      children/adolescents. OBJECTIVE: This study was aimed at examining the factorial
      structure of the Portuguese patient- and parent-reported versions of the
      DISABKIDS-Asthma Module (AsM) and its invariance across age groups and
      informants, as well as to examine their reliability and construct validity.
      METHODS: The sample included 140 children/adolescents aged 8-18 years, who were
      diagnosed with asthma, and one of their parents. Both family members assessed
      HrQoL at the generic (KIDSCREEN-10), chronic-generic (DISABKIDS-12) and asthma
      specific (DISABKIDS-AsM) levels. Asthma severity was classified by physicians
      using Global Initiative for Asthma (GINA) guidelines. RESULTS: Confirmatory
      factor analysis attested the factorial validity of the correlated two-factor
      model of the DISABKIDS-AsM, but the low average variance extracted by each factor
      (Impact and Worry) suggested that a one-factor structure would better fit the
      Portuguese data. The one-factor model had an acceptable fit (chi(2)/df = 1.97;
      comparative fit index = 0.94; root mean square error of approximation = 0.08) and
      was invariant between age groups (children vs. adolescents) and informants
      (patient-reports vs. parent-reports). The resulting global index of asthma
      specific HrQoL presented good reliability and convergent validity with the
      generic and chronic-generic measures. The DISABKIDS instruments also detected
      significant differences in HrQoL regarding asthma severity groups. CONCLUSIONS:
      The DISABKIDS-AsM may be regarded as a specific one-dimensional questionnaire,
      which, besides suiting pediatric patients in different developmental stages and
      enabling reliable proxy-reports, is sensitive to asthma clinical characteristics
      and is cross-culturally comparable, thus representing a valuable tool for
      assessing asthma-specific HrQoL as a primary health outcome in clinical practice
      and research contexts.

PMID- 24447286
TI  - In vivo reflectance confocal microscopy to optimize the spaghetti technique for
      defining surgical margins of lentigo maligna.
AB  - BACKGROUND: Lentigo maligna (LM) is a therapeutic challenge for surgeons because
      of its location in aesthetic areas and the difficulty in determining margins.
      OBJECTIVE: To investigate a new procedure combining the "spaghetti" technique
      described by Gaudy-Marqueste and colleagues in 2011 with in vivo reflectance
      confocal microscopy (RCM) to define the margins of LM more accurately and allow
      strict histologic control. METHODS AND MATERIALS: Thirty-three consecutive
      patients with LM of the head underwent a RCM-guided delineation of the margins
      followed by the "spaghetti" technique. RESULTS: The excision of the first
      "spaghetti" in a tumor-free area was obtained in 28 of 33 patients. In the other
      five cases, persistence of LM foci was found in <5% of the length of spaghetti.
      The average number of pieces of "spaghetti" was 1.2 (range 1-3). Definitive
      histologic examination of the lesion showed a minimum average margin of 2.7 mm.
      Follow-up in 27 patients after an average of 10 months (range 4-25 months) did
      not show any recurrence. CONCLUSION: This procedure allows accurate definition of
      the surgical margins of LM, with a low rate of multiple excisions, sparing tissue
      in functional and aesthetic areas. These results should be confirmed on the basis
      of a larger series with longer follow-up.

PMID- 24447287
TI  - Volitional chewing with a conscious effort alters and facilitates swallowing
      during feeding sequence.
AB  - The key objective of mastication is to form a food bolus suitable for smooth
      swallowing. However, chewing is usually performed without a conscious effort.
      Poor bolus formation can cause pharyngeal residue and suffocation in elderly
      individuals with reduced swallowing function. Therefore, chewing with a conscious
      effort may help the bolus to more easily pass the pharynx. This study aimed to
      clarify the impact of mastication with a conscious effort on the feeding
      sequence. Subjects included 25 dentulous volunteers who were informed and
      provided written consent. Lateral videofluoroscopy was performed during the
      feeding of solid agar jelly under two conditions: chewing naturally in their
      usual manner (without volition) and chewing with a conscious effort (with
      volition). Temporal evaluation was performed for mastication, stage II transport
      (STII), swallow onset and oropharyngeal transit time. Moreover, bolus volume at
      swallow onset and subjective evaluation of swallowing easiness were measured.
      Volitional chewing with a conscious effort lengthened the duration of the chewing
      sequence before and after STII and delayed the swallow onset despite the fact
      that the bolus volume in the vallecula and hypopharynx (HYP) had significantly
      increased. Furthermore, with volition, the bolus transit time from swallow onset
      in the oral cavity, upper oropharynx and HYP was reduced, and subjective
      evaluation of swallowing easiness demonstrated significant improvement. These
      results suggest that volitional chewing with a conscious effort can alter bolus
      transport and swallowing, resulting in easier swallowing. 

PMID- 24447288
TI  - Controlled particle collision leads to direct observation of docking and fusion
      of lipid droplets in an optical trap.
AB  - As an intracellular organelle, phospholipid-coated lipid droplets have shown
      increasing importance due to their expanding biological functions other than the
      lipid storage. The growing biological significance necessitates a close scrutiny
      on lipid droplets, which have been proposed to mature in a cell through processes
      such as fusion. Unlike phospholipid vesicles that are well-known to fuse through
      docking and hemifusion steps, little is known on the fusion of lipid droplets.
      Herein, we used laser tweezers to capture two micrometer-sized 1,2,3
      trioleoylglycerol (triolein) droplets coated with 1-palmitoyl-2-oleoyl-sn-glycero
      3-phosphocholine (POPC) that closely resemble intracellular lipid droplets. We
      started the fusion processes by a well-controlled collision between the two lipid
      droplets in phosphate buffer at pH 7.4. By monitoring the change in the pathway
      of a trapping laser that captures the collided lipid droplets, docking and
      physical fusion events were clearly distinguished for the first time and their
      lifetimes were determined with a resolution of 10 MUs after postsynchronization
      analysis. Our method revealed that the rate-limiting docking process is affected
      by anions according to a Hofmeister series, which sheds light on the important
      role of interfacial water shedding during the process. During the physical
      fusion, the kinetics between bare triolein droplets is faster than lipid
      droplets, suggesting that breaking of phospholipid coating is involved in the
      process. This scenario was further supported by direct observation of a short
      lived hemifusion state with ~46 ms lifetime in POPC-coated lipid droplets, but
      not in bare triolein droplets. 

PMID- 24447289
TI  - Optimization of carbon and nitrogen medium components for biomass production
      using non-Saccharomyces wine yeasts.
AB  - The impact of different nitrogen and carbon sources on biomass production of the
      non-Saccharomyces wine yeast species Lachancea thermotolerans, Metschnikowia
      pulcherrima and Issatchenkia orientalis was assessed. Using a molasses-based
      medium, yeast extract and corn steep liquor as well as ammonium sulphate and di
      ammonium phosphate (DAP) as nitrogen sources were compared in shake-flask
      cultures. A medium with 20 g l-1 sugar (diluted molasses) and 500 mg l-1 total
      yeast assimilable nitrogen, from yeast extract, gave the highest biomass
      concentrations and yields. Invertase pretreatment was required for cultures of M.
      pulcherrima and I. orientalis, and respective biomass yields of 0.7 and 0.8 g g-1
      were achieved in aerobic bioreactor cultures. The absence of ethanol production
      suggested Crabtree-negative behaviour by these yeasts, whereas Crabtree-positive
      behaviour by L. thermotolerans resulted in ethanol and biomass concentrations of
      5.5 and 11.1 g l-1, respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: Recent
      studies demonstrate that non-Saccharomyces yeasts confer positive attributes to
      the final composition of wine. However, optimal process conditions for their
      biomass production have not been described, thereby limiting commercial
      application. In this study, industrial media and methods of yeast cultivation
      were investigated to develop protocols for biomass production of non
      Saccharomyces yeast starter cultures for the wine industry.

PMID- 24447290
TI  - Impact of pain intensity on relationship quality between couples where one has
      back pain.
AB  - OBJECTIVES: To investigate associations of pain intensity in those with long-term
      back pain, with their partners' rating of key constructs of relationship quality:
      cohesion (activities together), consensus (affection, sexual relations),
      satisfaction (conflict, regrets). METHODS: Self-report questionnaires on
      relationship quality (partner-rated), depression (partner-rated), relationship
      length, and pain intensity (patient-rated) were collected from back pain patients
      and their partners (N = 71). Linear regression was carried out to test for
      associations, standardized coefficients (beta) and 95% confidence intervals (95%
      CI) are reported. RESULTS: There was no main effect between patient pain
      intensity and partner rating of relationship quality. However, partner ratings of
      relationship quality were lower if the partner reported increasing depressive
      symptoms. Adjusting for the effects of partner depression show that ratings of
      consensus (affection, sexual relations) from partners were actually higher with
      increasing levels of pain intensity in patients (beta 0.54, 95% CI 0.17 to 0.90,
      P < 0.01). Furthermore lower ratings of consensus were reported where patient
      pain intensity interacted with partner depression (beta -0.11, 95% CI-0.19 to 
      0.03, P < 0.05). CONCLUSIONS: These findings illustrate the association of pain
      outcomes beyond the patient within a primary care sample. Moderators of the
      responses about the relationship construct of consensus generated by partners
      appear to be partners' own level of depressive symptoms and whether their
      depressive symptoms are associated with the patients' pain intensity.
      Consultations should consider the social context of patients with pain.

PMID- 24447291
TI  - Evaluating the effectiveness of teeth and dorsal fin spines for non-lethal age
      estimation of a tropical reef fish, coral trout Plectropomus leopardus.
AB  - This study investigated whether teeth and dorsal fin spines could be used as non
      lethal methods of age estimation for a vulnerable and highly valued tropical
      fisheries species, coral trout Plectropomus leopardus. Age estimation of
      individuals from 2 to 9 years old revealed that dorsal spines represent an
      accurate ageing method (90% agreement with otoliths) that was more precise
      [average per cent error (APE) = 4.1, coefficient of variation (c.v.) = 5.8%] than
      otoliths (APE = 6.2, c.v. = 8.7%). Of the three methods for age estimation
      (otoliths, dorsal spines and teeth), spines were the most time and cost
      efficient. An aquarium-based study also found that removing a dorsal spine or
      tooth did not affect survivorship or growth of P. leopardus. No annuli were
      visible in teeth despite taking transverse and longitudinal sections throughout
      the tooth and trialling several different laboratory methods. Although teeth may
      not be suitable for estimating age of P. leopardus, dorsal spines appear to be an
      acceptably accurate, precise and efficient method for non-lethal ageing of
      individuals from 2 to 9 years old in this tropical species. 

PMID- 24447292
TI  - Enigma of urethral pain syndrome: why are there so many ascribed etiologies and
      therapeutic approaches?
AB  - Urethral pain syndrome has had several sobriquets, which have led to much
      confusion over the existence of this pathological condition and the useful
      options in the care of the afflicted patient. Our aim was to explore the proposed
      etiologies of this syndrome, and to provide a critical analysis of each proposed
      etiology and present a balanced argument on the plausibility of the proposed
      etiology and therapeutic approaches. We carried out an English language
      electronic search in the following databases: Medline, Embase, Amed, Cinahl,
      Pubmed, Cochrane Library, Trip Database and SUMSearch using the following search
      terms: urethral syndrome, urethral diseases, urethra, urologic diseases
      etiology/etiology, presentation, treatment, outcome, therapeutics and treatment
      from 1951 to 2011. In excess of 200 articles were recovered. With the clearly
      defined objectives of analyzing the proposed etiologies and therapeutic regimes,
      two author(s) (HP and IO) perused the abstracts of all the recovered articles,
      selecting those that addressed the etiologies and therapeutic approaches to
      treating the urethral pain syndrome. The number of articles was reduced to 25.
      The full text of all 25 articles were retrieved and reviewed. Through the present
      article, we hope to elucidate the most probable etiology of this condition whilst
      simultaneously, advance a logical explanation for the apparent success in the
      treatment of this condition using a range of different therapeutic modalities. We
      have carried out a narrative review, which we hope will reduce some of the
      confusion around this clinical entity by combining the known facts about the
      disease. 

PMID- 24447293
TI  - Impact of three-dimensional imaging and pressure recovery on echocardiographic
      evaluation of severe aortic stenosis: a pilot study.
AB  - AIMS: In patients with aortic stenosis (AS), echocardiographic grading of
      stenosis severity is important, in particular for transcatheter aortic valve
      implantation (TAVI). Three-dimensional (3D) echocardiography and correction for
      pressure recovery (PR) by energy loss index (ELI) may improve aortic valve area
      (AVA) calculation. METHODS AND RESULTS: Thirty-nine patients with severe AS
      evaluated for TAVI were included. Left ventricular outflow tract (LVOT) and
      ascending aorta (AA) cross-sectional area were determined in transthoracic two
      dimensional echocardiography (2DTTE), 2D transesophageal echocardiography (TEE),
      3DTEE, and multislice computed tomography (MSCT). AVA was calculated by the
      continuity equation and corrected for PR. ELI was determined as [(AVA * AA)/(AA -
      AVA)]/body surface area. LVOT area was 2.41 +/- 0.17 cm(2) calculated using
      2DTTE, 2.82 +/- 0.16 cm(2) calculated using 2DTEE, 3.96 +/- 0.14 cm(2)
      planimetered in 3DTEE, and 4.47 +/- 0.18 cm(2) planimetered in MSCT (P < 0.001).
      AA area was 4.62 +/- 0.23 cm(2) calculated using 2DTTE, 4.64 +/- 0.23 cm(2)
      calculated using 2DTEE, 5.35 +/- 0.25 cm(2) planimetered in 3DTEE, and 6.56 +/-
      0.31 cm(2) planimetered in MSCT (P < 0.001). Indexed aortic valve area (AVAI)
      calculated by 2DTTE and 2DTEE was smaller (0.27 +/- 0.02 cm(2) /m(2) and 0.32 +/-
      0.02 cm(2) /m(2) ) compared to 3DTEE (0.45 +/- 0.02 cm(2) /m(2) ; P < 0.001).
      When AVAI determined by 3DTEE was corrected for PR by calculation of ELI, there
      was a further increase (0.52 +/- 0.03 cm(2) /m(2) ; P < 0.001), and 10/36 (27.8%)
      patients were reclassified to moderate AS. CONCLUSION: Three-dimensional TEE is
      more accurate than 2DTTE and 2DTEE for determining LVOT and AA dimensions. When
      AS severity is determined by 3DTEE and corrected for PR using the 3D values, it
      needs to be reclassified from severe to moderate in almost a third of patients.

PMID- 24447294
TI  - Inactivation of Bacillus subtilis spores using various combinations of
      ultraviolet treatment with addition of hydrogen peroxide.
AB  - This study aims at comparing the inactivation of Bacillus subtilis spores by
      various combinations of UV treatment and hydrogen peroxide (H2O2) addition. The
      combinations included sequential (UV-H2O2, H2O2-UV) and simultaneous (UV/H2O2)
      processes. Results showed that B. subtilis spores achieved a certain inactivation
      effect through UV treatment. However, hardly any inactivation effect by H2O2
      alone was observed. H2O2 had a significant synergetic effect when combined with
      UV treatment, while high irradiance and H2O2 concentration both favored the
      reaction. When treated with 0.60 mm H2O2 and 113.0 MUW/cm(2) UV irradiance for 6
      min, the simultaneous UV/H2O2 treatment showed significantly improved
      disinfection effect (4.13 log) compared to that of UV-H2O2 (3.03 log) and H2O2-UV
      (2.88 log). The relationship between the inactivation effect and the exposure
      time followed a typical pseudo-first-order kinetics model. The pseudo-first-order
      rate constants were 0.478, 0.447 and 0.634 min(-1), for the UV-H2O2, H2O2-UV and
      UV/H2O2 processes, respectively, further confirming the optimal disinfection
      effect of the UV/H2O2 process. The disinfection could be ascribed to the OH
      radicals, as verified by the level of para-chlorobenzoic acid (pCBA).

PMID- 24447295
TI  - Raman scattering in molecular junctions: a pseudoparticle formulation.
AB  - We present a formulation of Raman spectroscopy in molecular junctions based on a
      many-body state representation of the molecule. The approach goes beyond the
      previous effective single orbital formalism and provides a convenient way to
      incorporate computational methods and tools proven for equilibrium molecular
      spectroscopy into the realm of current carrying junctions. The presented
      framework is illustrated by first principle simulations of Raman response in a
      three-ring oligophenylene vinylene terminating in amine functional groups (OPV3)
      junction. The calculated shift in Stokes lines and estimate of vibrational
      heating by electric current agree with available experimental data. In
      particular, our results suggest that participation of the OPV3 cation in Raman
      scattering under bias may be responsible for the observed shift, and that the
      direction of the shift depends on renormalization of normal modes. This work is a
      step toward atomistic quantum ab initio modeling of the optical response of
      nonequilibrium electronic dynamics in molecular junctions. 

PMID- 24447296
TI  - Intranasal dexmedetomidine following failed chloral hydrate sedation in children.
AB  - Chloral hydrate is the most commonly used sedative for paediatric diagnostic
      procedures in China with a success rate of around 80%. Intranasal dexmedetomidine
      is used for rescue sedation in our centre. This prospective investigation
      evaluated 213 children aged one month to 10 years who were not adequately sedated
      following administration of chloral hydrate. Children were randomly assigned to
      receive rescue intranasal dexmedetomidine at 1 MUg.kg(-1) (group 1), 1.5 MUg.kg(
      1) (group 2) or 2 MUg.kg(-1) (group 3). The sedation level was assessed every 10
      min using a modified observer's assessment of alertness/sedation scale.
      Successful rescue sedation in groups 1, 2 and 3 were 56 (83.6%), 66 (89.2%) and
      51 (96.2%), respectively. Increasing the rescue dose was associated with an
      increased success rate with an odds ratio of 4.12 (95% CI 1.13-14.98), p = 0.032.
      We conclude that intranasal dexmedetomidine is effective for sedation in children
      who do not respond to chloral hydrate. 

PMID- 24447297
TI  - Mycobacterium tuberculosis type II NADH-menaquinone oxidoreductase catalyzes
      electron transfer through a two-site ping-pong mechanism and has two quinone
      binding sites.
AB  - Type II NADH-quinone oxidoreductase (NDH-2) catalyzes the transfer electrons from
      NADH to the quinone pool and plays an essential role in the oxidative
      phosphorylation system of Mycobacterium tuberculosis (Mtb). The absence of NDH-2
      in the mammalian mitochondrial electron transport chain makes this enzyme an
      attractive target for antibiotic development. To fully establish the kinetic
      properties of this enzyme, we studied the interaction of Mtb NDH-2 with
      substrates, NADH, and various quinone analogues and their products in both
      membrane and soluble environments. These studies, and comparative analyses of the
      kinetics with thio-NAD(+) and quinone electron acceptors, provided evidence that
      Mtb NDH-2 catalyzes the transfer electrons from NADH to quinone substrates by a
      nonclassical, two-site ping-pong kinetic mechanism whereby substrate quinones
      bind to a site that is distinct from the NADH-binding site. Furthermore, the
      effects of quinols on Mtb NDH-2 catalytic activity demonstrate the presence of
      two binding sites for quinone ligands, one favoring the reduced form and the
      other favoring the oxidized form. 

PMID- 24447298
TI  - LDL receptor/lipoprotein recognition: endosomal weakening of ApoB and ApoE
      binding to the convex face of the LR5 repeat.
AB  - The molecular mechanism of lipoprotein binding by the low-density lipoprotein
      (LDL) receptor (LDLR) is poorly understood, one reason being that structures of
      lipoprotein-receptor complexes are not available. LDLR uses calcium-binding
      repeats (LRs) to interact with apolipoprotein B and apolipoprotein E (ApoB and
      ApoE). We have used NMR and SPR to characterize the complexes formed by LR5 and
      three peptides encompassing the putative binding regions of ApoB (site A and site
      B) and ApoE. The three peptides bind at the hydrophilic convex face of LR5,
      forming complexes that are weakened at low [Ca(2+) ] and low pH. Thus, endosomal
      conditions favour dissociation of LDLR/lipoprotein complexes regardless of
      whether active displacement of bound lipoproteins by the beta-propeller in LDLR
      takes place. The multiple ApoE copies in beta very low density lipoproteins (beta
      VLDLs), and the presence of two competent binding sites (A and B) in LDLs,
      suggest that LDLR chelates lipoproteins and enhances complex affinity by using
      more than one LR.

PMID- 24447301
TI  - Bacteria and diatom resistance of silicones modified with PEO-silane amphiphiles.
AB  - Silicone coatings with enhanced antifouling behavior towards bacteria, diatoms,
      and a diatom dominated slime were prepared by incorporating PEO-silane
      amphiphiles with varied siloxane tether lengths (a-c): alpha-(EtO)3Si(CH2)2
      oligodimethylsiloxanen-block-poly(ethylene oxide)8-OCH3 [n = 0 (a), 4 (b), and 13
      (c)]. Three modified silicone coatings (A-C) were prepared by the acid-catalyzed
      sol-gel cross-linking of a-c, respectively, each with a stoichiometric 2:3 M
      ratio of alpha, omega-bis(Si-OH)polydimethylsiloxane (Mn = 3,000 g mol(-1)). The
      coatings were exposed to the marine bacterium Bacillus sp.416 and the diatom
      (microalga) Cylindrotheca closterium, as well as a mixed community of Bacillus
      sp. and C. closterium. In addition, in situ microfouling was assessed by
      maintaining the coatings in the Atlantic Ocean. Under all test conditions,
      biofouling was reduced to the highest extent on coating C which was prepared with
      the PEO-silane amphiphile having the longest siloxane tether length (c).

PMID- 24447299
TI  - Ultraviolet photodissociation for characterization of whole proteins on a
      chromatographic time scale.
AB  - Intact protein characterization using mass spectrometry thus far has been
      achieved at the cost of throughput. Presented here is the application of 193 nm
      ultraviolet photodissociation (UVPD) for top down identification and
      characterization of proteins in complex mixtures in an online fashion. Liquid
      chromatographic separation at the intact protein level coupled with fast UVPD and
      high-resolution detection resulted in confident identification of 46 unique
      sequences compared to 44 using HCD from prepared Escherichia coli ribosomes.
      Importantly, nearly all proteins identified in both the UVPD and optimized HCD
      analyses demonstrated a substantial increase in confidence in identification (as
      defined by an average decrease in E value of ~40 orders of magnitude) due to the
      higher number of matched fragment ions. Also shown is the potential for high
      throughput characterization of intact proteins via liquid chromatography (LC)
      UVPD-MS of molecular weight-based fractions of a Saccharomyces cerevisiae lysate.
      In total, protein products from 215 genes were identified and found in 292
      distinct proteoforms, 168 of which contained some type of post-translational
      modification. 

PMID- 24447302
TI  - Evaluation of P300 components for emotion-loaded visual event-related potential
      in elderly subjects, including those with dementia.
AB  - AIM: In the present study, the P300 component of the emotion-loaded visual event
      related potential in response to photographs of babies crying or smiling was
      measured to evaluate cognitive function in elderly subjects, including those with
      dementia. METHODS: The subjects were 48 elderly people who consulted a memory
      disorder clinic. The visual event-related potential was measured using oddball
      tasks. Brain waves were recorded from four sites. We analyzed the P300 amplitude
      and latency. Subjects were divided into three groups (the dementia with
      Alzheimer's disease group [ADG]; the intermediate group [MG], and the healthy
      group [HG]) based on the Revised Hasegawa Dementia Scale, Mini-mental State
      Examination scores and the Clinical Dementia Rating. RESULTS: For all subjects,
      there was a significant positive correlation between P300 latency and Z-score of
      voxel-based specific regional analysis for Alzheimer's disease for crying or
      smiling faces. There was a negative correlation between P300 amplitude and Z
      score for the crying face. MG subjects were divided into two groups (high risk:
      HRMG, low risk: LRMG) based on Z-scores (HRMG >= 2.0). The P300 amplitude of ADG
      was significantly smaller than that of HG, and the P300 latency of ADG was
      significantly longer than those of other groups for crying or smiling faces. The
      P300 latency of HRMG was significantly longer than that of LRMG for the smiling
      face. Furthermore, the P300 latency for the crying face was significantly shorter
      than that for the smiling face in HG and ADG. CONCLUSION: These findings suggest
      that analysis of P300 components of the emotion-loaded visual event-related
      potential may be a useful neuropsychological index for the diagnosis of
      Alzheimer's disease and high-risk subjects.

PMID- 24447303
TI  - Genetic and phenotypic divergence in an island bird: isolation by distance, by
      colonization or by adaptation?
AB  - Discerning the relative roles of adaptive and nonadaptive processes in generating
      differences among populations and species, as well as how these processes
      interact, is a fundamental aim in biology. Both genetic and phenotypic divergence
      across populations can be the product of limited dispersal and gradual genetic
      drift across populations (isolation by distance), of colonization history and
      founder effects (isolation by colonization) or of adaptation to different
      environments preventing migration between populations (isolation by adaptation).
      Here, we attempt to differentiate between these processes using island
      populations of Berthelot's pipit (Anthus berthelotii), a passerine bird endemic
      to three Atlantic archipelagos. Using microsatellite markers and approximate
      Bayesian computation, we reveal that the northward colonization of this species
      ca. 8500 years ago resulted in genetic bottlenecks in the colonized archipelagos.
      We then show that high levels of genetic structure exist across archipelagos and
      that these are consistent with a pattern of isolation by colonization, but not
      with isolation by distance or adaptation. Finally, we show that substantial
      morphological divergence also exists and that this is strongly concordant with
      patterns of genetic structure and bottleneck history, but not with environmental
      differences or geographic distance. Overall, our data suggest that founder
      effects are responsible for both genetic and phenotypic changes across
      archipelagos. Our findings provide a rare example of how founder effects can
      persist over evolutionary timescales and suggest that they may play an important
      role in the early stages of speciation. 

PMID- 24447305
TI  - Engineering in situ cross-linkable and neurocompatible hydrogels.
AB  - Physical injuries of the central nervous system (CNS) are prevalent and very
      severe because the CNS has limited capacity to replace neuronal loss from the
      injury. A growing body of evidence has suggested that exogenous cell
      transplantation is one promising strategy to promote CNS regeneration. Direct
      injection of neural stem cells (NSCs) to the lesion site, however, may not be an
      optimal therapeutic strategy because of poor viability and functionality of
      transplanted cells resulting from the local hostile tissue environment. The
      overall objective of this study is to engineer an injectable and biocompatible
      hydrogel system as a supportive niche to provide a regeneration permissive
      microenvironment for transplanted NSCs to survive, functionally differentiate,
      and integrate with host tissues for CNS regeneration. A highly biocompatible
      hydrogel, based on thiol functionalized hyaluronic acid and thiol functionalized
      gelatin (Gtn-SH), which can be cross-linked by poly(ethylene glycol) diacrylate
      (PEGDA), was used. By controlling the cross-linking density via varying the
      amount of cross-linker (PEGDA) and the concentration of the adhesive component
      gelatin, an optimal microenvironment for the survival, proliferation, and
      neuronal differentiation of NSCs was created in vitro. The soft hydrogel of less
      than 10 Pa with Gtn-SH content (50%) is one of the optimal conditions to support
      NSCs growth and neuronal differentiation in vitro. The optimized hydrogel holds
      great potential as a carrier of stem cells to treat CNS injuries and diseases in
      which cell therapies may be essential.

PMID- 24447304
TI  - Novel treatment option for MUC16-positive malignancies with the targeted TRAIL
      based fusion protein Meso-TR3.
AB  - BACKGROUND: The targeted delivery of cancer therapeutics represents an ongoing
      challenge in the field of drug development. TRAIL is a promising cancer drug but
      its activity profile could benefit from a cancer-selective delivery mechanism,
      which would reduce potential side effects and increase treatment efficiencies. We
      recently developed the novel TRAIL-based drug platform TR3, a genetically fused
      trimer with the capacity for further molecular modifications such as the addition
      of tumor-directed targeting moieties. MUC16 (CA125) is a well characterized
      biomarker in several human malignancies including ovarian, pancreatic and breast
      cancer. Mesothelin is known to interact with MUC16 with high affinity. In order
      to deliver TR3 selectively to MUC16-expressing cancers, we investigated the
      possibility of targeted TR3 delivery employing the high affinity mesothelin/MUC16
      ligand/receptor interaction. METHODS: Using genetic engineering, we designed the
      novel cancer drug Meso-TR3, a fusion protein between native mesothelin and TR3.
      The recombinant proteins were produced with mammalian HEK293T cells. Meso-TR3 was
      characterized for binding selectivity and killing efficacy against MUC16-positive
      cancer cells and controls that lack MUC16 expression. Drug efficacy experiments
      were performed in vitro and in vivo employing an intraperitoneal xenograft mouse
      model of ovarian cancer. RESULTS: Similar to soluble mesothelin itself, the
      strong MUC16 binding property was retained in the Meso-TR3 fusion protein. The
      high affinity ligand/receptor interaction was associated with a selective
      accumulation of the cancer drug on MUC16-expressing cancer targets and directly
      correlated with increased killing activity in vitro and in a xenograft mouse
      model of ovarian cancer. The relevance of the mesothelin/MUC16 interaction for
      attaching Meso-TR3 to the cancer cells was verified by competitive blocking
      experiments using soluble mesothelin. Mechanistic studies using soluble DR5-Fc
      and caspase blocking assays confirmed engagement of the extrinsic death receptor
      pathway. Compared to non-targeted TR3, Meso-TR3 displayed a much reduced killing
      potency on cells that lack MUC16. CONCLUSIONS: Soluble Meso-TR3 targets the
      cancer biomarker MUC16 in vitro and in vivo. Following attachment to the tumor
      via surface bound MUC16, Meso-TR3 acquires full activation with superior killing
      profiles compared to non-targeted TR3, while its bioactivity is substantially
      reduced on cells that lack the tumor marker. This prodrug phenomenon represents a
      highly desirable property because it has the potential to enhance cancer killing
      with fewer side-effects than non-targeted TRAIL-based therapeutics. Thus, further
      exploration of this novel fusion protein is warranted as a possible therapeutic
      for patients with MUC16-positive malignancies.

PMID- 24447306
TI  - Recovery of neurological function of ischemic stroke by application of
      conditioned medium of bone marrow mesenchymal stem cells derived from normal and
      cerebral ischemia rats.
AB  - BACKGROUND: Several lines of evidence have demonstrated that bone marrow-derived
      mesenchymal stem cells (BM-MSC) release bioactive factors and provide
      neuroprotection for CNS injury. However, it remains elusive whether BM-MSC
      derived from healthy donors or stroke patients provides equal therapeutic
      potential. The present work aims to characterize BM-MSC prepared from normal
      healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine
      the effects of their conditioned medium (Cm) on ischemic stroke animal model.
      RESULTS: Isolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology
      and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker
      CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC
      than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated
      mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC
      was further examined in cultures and in middle cerebral artery occlusion (MCAo)
      animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal
      connection and survival in mixed neuron-glial cultures. In vivo, intravenous
      infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably
      improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm
      increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo
      rat brains. CONCLUSIONS: Our data suggest equal effectiveness of BM-MSC Cm
      derived from ischemic animals or from a normal population. Our results thus
      revealed the potential of BM-MSC Cm on treatment of ischemic stroke.

PMID- 24447307
TI  - Inpatient hyperglycaemia improvement quality program.
AB  - BACKGROUND: Poorly controlled hyperglycaemia is associated with increased
      morbidity and mortality in hospitalised patients. Based on the view that
      hospitalisation provides a window of opportunity to improve patient quality of
      care and health status, a comprehensive program for treating hospitalised
      diabetic patients was initiated. This study assessed the effectiveness of the
      Inpatient Hyperglycaemia Improvement Quality Program (IHIQP) over a 4-year
      period. METHODS: Pre-test post-test design. In the pre-intervention period
      (August-December 2007), an institution-wide blood glucose monitoring system was
      introduced in August 2007. The remaining program components were introduced in
      January 2008, including implementing a hospital care protocol based on the 2007
      American Diabetes Association Standards, a multidisciplinary team that
      participates in patient care and arranges continuing care after discharge and
      comprehensive patient education prior to discharge. Program results from January
      2008 through October 2011 were evaluated. RESULTS: During follow-up, more than
      600,000 blood glucose tests were performed. Blood glucose values declined from
      196.4 +/- 98.4 mg/dl pre-IHIQP (August-December 2007) to 174.5 +/- 82.0 mg/dl
      post-IHIQP (January-October 2011) (p < 0.0001). Prevalence of glucose values
      lower than 60 mg/dl declined from 2% to 1.3% (p < 0.004). Prevalence of glucose
      values >= 300 mg/dl declined from 13.6% to 8.4% (p < 0.0001). Concomitantly, the
      proportion of in-target values of 80-180 mg/dl increased from 47.7% to 58.1% (p <
      0.0001). CONCLUSION: This in-patient hyperglycaemia quality improvement program
      led to improvements in-patient glycaemic control, which continued over time. The
      effect of this improvement on in-patient mortality and morbidity needs additional
      follow-up.

PMID- 24447308
TI  - Acidosis and hyperkalemia caused by losartan and enalapril in pediatric kidney
      transplant recipients.
AB  - OBJECTIVES: To evaluate the efficacy and safety of losartan and enalapril in
      pediatric kidney transplant recipients. MATERIALS AND METHODS: A retrospective
      review was performed in 31 pediatric kidney transplant recipients who were
      treated with losartan (50 mg/d, oral) for 1 to 6 months because of mild
      hypertension and persistent proteinuria. All patients were treated concurrently
      with enalapril (5 or 10 mg daily, oral), and 12 patients (39%) also were treated
      with amlodipine (5 or 10 mg daily, oral). Demographic and clinical
      characteristics of the patients were reviewed. RESULTS: Losartan use was
      associated with a significant decrease in mean systolic (before losartan was
      started, 123 +/- 14 mm Hg; before losartan was stopped, 111 +/- 10 mm Hg; P <=
      .001) and diastolic blood pressure (before losartan was started, 78 +/- 11 mm Hg;
      before losartan was stopped, 69 +/- 10 mm Hg; P <= .001) and urinary protein
      excretion (before losartan was started, 51 +/- 45 mg/m2/h; before losartan was
      stopped, 28 +/- 34 mg/m2/h; P <= .001). However, losartan therapy was associated
      with a significant mean increase in serum potassium level (before losartan was
      started, 4.0 +/- 0.4 mmol/L; before losartan was stopped, 5.7 +/- 0.5 mmol/L; P
      <= .001) and decrease in pH (before losartan was started, 7.35 +/- 0.0; before
      losartan was stopped, 7.23 +/- 0.0; P <= .001). Losartan was stopped because of
      hyperkalemia and acidosis earlier in patients who were on tacrolimus than
      cyclosporine immunosuppression (tacrolimus, 3 +/- 1 mo; cyclosporine, 4.7 +/- 0.8
      mo; P <= .001). CONCLUSIONS: Losartan and enalapril may be beneficial in
      pediatric kidney transplant recipients by decreasing blood pressure and
      proteinuria, with maintenance of stable graft function, but may be associated
      with serious adverse events including hyperkalemia and life-threatening acidosis.

PMID- 24447309
TI  - Substandard urological care of elderly patients with spinal cord injury: an
      unrecognized epidemic?
AB  - BACKGROUND: We report the anecdotal observation of substandard urological care of
      elderly paraplegic patients in the community suffering from long-term sequelae of
      spinal cord injuries. This article is designed to increase awareness of a problem
      that is likely underreported and may represent the 'tip of the iceberg' related
      to substandard care provided to the vulnerable population of elderly patients
      with chronic neurological impairment. FINDINGS: A registered Nurse changed the
      urethral catheter of an 80-year-old-male with paraplegia; patient developed
      profuse urethral bleeding and septicaemia. Ultrasound revealed balloon of Foley
      catheter located in membranous urethra. Flexible cystoscopy was performed and a
      catheter was inserted over a guide wire. Urethral bleeding recurred 12 days
      later. This patient was discharged after protracted stay in spinal unit. A nurse
      changed urethral catheter in an 82-year-old male with paraplegia. The catheter
      did not drain urine; patient developed pain in lower abdomen. The balloon of
      Foley catheter was visible behind the urethral meatus, which indicated that the
      balloon had been inflated in penile urethra. The catheter was removed and a 16
      French Foley catheter was inserted per urethra. About 1300 ml of urine was
      drained. A 91-year-old lady with paraplegia underwent routine ultrasound
      examination of urinary tract by a Consultant Radiologist, who reported a 4 cm * 3
      cm soft tissue mass in the urinary bladder. Cystoscopy was performed without
      anaesthesia in lithotomy position. Cystoscopy revealed normal bladder mucosa; no
      stones; no tumour. Following cystoscopy, the right knee became swollen and there
      was deformity of lower third of right thigh. X-ray revealed fracture of lower
      third of right femur. Femoral fracture was treated by immobilisation in full
      plaster cast. Follow-up ultrasound examination of urinary tract, performed by a
      senior Radiologist, revealed normal outline of urinary bladder with no tumour or
      calculus. CONCLUSION: The adverse outcomes can be averted if elderly spinal cord
      injury patients are treated by senior, experienced health professionals, who are
      familiar with changes in body systems due to old age, compounded further by
      spinal cord injury.

PMID- 24447310
TI  - Cost-effective length and timing of school closure during an influenza pandemic
      depend on the severity.
AB  - BACKGROUND: There has been a variation in published opinions toward the
      effectiveness of school closure which is implemented reactively when substantial
      influenza transmissions are seen at schools. Parameterizing an age-structured
      epidemic model using published estimates of the pandemic H1N1-2009 and accounting
      for the cost effectiveness, we examined if the timing and length of school
      closure could be optimized. METHODS: Age-structured renewal equation was employed
      to describe the epidemic dynamics of an influenza pandemic. School closure was
      assumed to take place only once during the course of the pandemic, abruptly
      reducing child-to-child transmission for a fixed length of time and also
      influencing the transmission between children and adults. Public health
      effectiveness was measured by reduction in the cumulative incidence, and cost
      effectiveness was also examined by calculating the incremental cost effectiveness
      ratio and adopting a threshold of 1.0 * 107 Japanese Yen/life-year. RESULTS:
      School closure at the epidemic peak appeared to yield the largest reduction in
      the final size, while the time of epidemic peak was shown to depend on the
      transmissibility. As the length of school closure was extended, we observed
      larger reduction in the cumulative incidence. Nevertheless, the cost
      effectiveness analysis showed that the cost of our school closure scenario with
      the parameters derived from H1N1-2009 was not justifiable. If the risk of death
      is three times or greater than that of H1N1-2009, the school closure could be
      regarded as cost effective. CONCLUSIONS: There is no fixed timing and duration of
      school closure that can be recommended as universal guideline for different types
      of influenza viruses. The effectiveness of school closure depends on the
      transmission dynamics of a particular influenza virus strain, especially the
      virulence (i.e. the infection fatality risk).

PMID- 24447311
TI  - Improving the dielectric properties of ethylene-glycol alkanethiol self-assembled
      monolayers.
AB  - Self-assembled monolayers (SAMs) can be formed at the interface between solids
      and fluids, and are often used to modify the surface properties of the solid. One
      of the most widely employed SAM systems is exploiting thiol-gold chemistry,
      which, together with alkane-chain-based molecules, provides a reliable way of SAM
      formation to modify the surface properties of electrodes. Oligo ethylene-glycol
      (OEG) terminated alkanethiol monolayers have shown excellent antifouling
      properties and have been used extensively for the coating of biosensor electrodes
      to minimize nonspecific binding. Here, we report the investigation of the
      dielectric properties of COOH-capped OEG monolayers and demonstrate a strategy to
      improve the dielectric properties significantly by mixing the OEG SAM with small
      concentrations of 11-mercaptoundecanol (MUD). The monolayer properties and
      composition were characterized by means of impedance spectroscopy, water contact
      angle, ellipsometry and X-ray photoelectron spectroscopy. An equivalent circuit
      model is proposed to interpret the EIS data and to determine the conductivity of
      the monolayer. We find that for increasing MUD concentrations up to about 5% the
      resistivity of the SAM steadily increases, which together with a considerable
      decrease of the phase of the impedance, demonstrates significantly improved
      dielectric properties of the monolayer. Such monolayers will find widespread use
      in applications which depend critically on good dielectric properties such as
      capacitive biosensor. 

PMID- 24447312
TI  - Penetration approach for repeat vertebroplasty through the previously impacted
      bone cement.

PMID- 24447314
TI  - Commentary: Individual vs. weight-based dosing of azathioprine in Crohn's
      disease.

PMID- 24447313
TI  - Increased anxiety in corticotropin-releasing factor type 2 receptor-null mice
      requires recent acute stress exposure and is associated with dysregulated
      serotonergic activity in limbic brain areas.
AB  - BACKGROUND: Corticotropin-releasing factor type 2 receptors (CRFR2) are suggested
      to facilitate successful recovery from stress to maintain mental health. They are
      abundant in the midbrain raphe nuclei, where they regulate serotonergic neuronal
      activity and have been demonstrated to mediate behavioural consequences of
      stress. Here, we describe behavioural and serotonergic responses consistent with
      maladaptive recovery from stressful challenge in CRFR2-null mice. RESULTS: CRFR2
      null mice showed similar anxiety levels to control mice before and immediately
      after acute restraint stress, and also after cessation of chronic stress.
      However, they showed increased anxiety by 24 hours after restraint, whether or
      not they had been chronically stressed.Serotonin (5-HT) and 5-hydroxyindoleacetic
      acid (5-HIAA) contents were quantified and the level of 5-HIAA in the caudal
      dorsal raphe nucleus (DRN) was increased under basal conditions in CRFR2-null
      mice, indicating increased 5-HT turnover. Twenty-four hours following restraint,
      5-HIAA was decreased only in CRFR2-null mice, suggesting that they had not fully
      recovered from the challenge. In efferent limbic structures, CRFR2-null mice
      showed lower levels of basal 5-HT in the lateral septum and subiculum, and again
      showed a differential response to restraint stress from controls.Local cerebral
      glucose utilization (LCMRglu) revealed decreased neuronal activity in the DRN of
      CRFR2-null mice under basal conditions. Following 5-HT receptor agonist
      challenge, LCMRglu responses indicated that 5-HT1A receptor responses in the DRN
      were attenuated in CRFR2-null mice. However, postsynaptic 5-HT receptor responses
      in forebrain regions were intact. CONCLUSIONS: These results suggest that CRFR2
      are required for proper functionality of 5-HT1A receptors in the raphe nuclei,
      and are key to successful recovery from stress. This disrupted serotonergic
      function in CRFR2-null mice likely contributes to their stress-sensitive
      phenotype. The 5-HT content in lateral septum and subiculum was notably altered.
      These areas are important for anxiety, and are also implicated in reward and the
      pathophysiology of addiction. The role of CRFR2 in stress-related
      psychopathologies deserves further consideration.

PMID- 24447315
TI  - Letter: Azathioprine-induced pancreatitis and subsequent tolerance of
      mercaptopurine.

PMID- 24447316
TI  - Letter: Azathioprine-induced pancreatitis and subsequent tolerance of
      mercaptopurine--authors' reply.

PMID- 24447317
TI  - Letter: Treatment for small intestinal bacterial overgrowth--where are we now?
      Authors' reply.

PMID- 24447318
TI  - Letter: Treatment for small intestinal bacterial overgrowth--where are we now?

PMID- 24447319
TI  - Letter: Pitavastatin supplementation of PEG-IFN/ribavirin improves sustained
      virological response against HCV.

PMID- 24447320
TI  - Letter: The feasibility and safety of accelerated infliximab infusions in
      patients with inflammatory bowel disease.

PMID- 24447321
TI  - Barriers and facilitators in the provision of post-abortion care at district
      level in central Uganda - a qualitative study focusing on task sharing between
      physicians and midwives.
AB  - BACKGROUND: Abortion is restricted in Uganda, and poor access to contraceptive
      methods result in unwanted pregnancies. This leaves women no other choice than
      unsafe abortion, thus placing a great burden on the Ugandan health system and
      making unsafe abortion one of the major contributors to maternal mortality and
      morbidity in Uganda. The existing sexual and reproductive health policy in Uganda
      supports the sharing of tasks in post-abortion care. This task sharing is taking
      place as a pragmatic response to the increased workload. This study aims to
      explore physicians' and midwives' perception of post-abortion care with regard to
      professional competences, methods, contraceptive counselling and task
      shifting/sharing in post-abortion care. METHODS: In-depth interviews (n = 27)
      with health care providers of post-abortion care were conducted in seven health
      facilities in the Central Region of Uganda. The data were organized using
      thematic analysis with an inductive approach. RESULTS: Post-abortion care was
      perceived as necessary, albeit controversial and sometimes difficult to provide.
      Together with poor conditions post-abortion care provoked frustration especially
      among midwives. Task sharing was generally taking place and midwives were
      identified as the main providers, although they would rarely have the proper
      training in post-abortion care. Additionally, midwives were sometimes forced to
      provide services outside their defined task area, due to the absence of doctors.
      Different uterine evacuation skills were recognized although few providers knew
      of misoprostol as a method for post-abortion care. An overall need for further
      training in post-abortion care was identified. CONCLUSIONS: Task sharing is
      taking place, but providers lack the relevant skills for the provision of quality
      care. For post-abortion care to improve, task sharing needs to be scaled up and
      in-service training for both doctors and midwives needs to be provided. Post
      abortion care should further be included in the educational curricula of nurses
      and midwives. Scaled-up task sharing in post-abortion care, along with
      misoprostol use for uterine evacuation would provide a systematic approach to
      improving the quality of care and accessibility of services, with the aim of
      reducing abortion-related mortality and morbidity in Uganda.

PMID- 24447322
TI  - Trophic size-structure of sailfish Istiophorus platypterus in eastern Taiwan
      estimated by stable isotope analysis.
AB  - To examine trophic dynamics over different size classes, an isotopic study of
      sailfish Istiophorus platypterus life-history stages was carried out. Samples
      were collected from eastern Taiwan and the South China Sea during April 2009 and
      February 2012. A total of 263 samples (111-245 cm, lower jaw fork length, LLJFL )
      were examined for changes in trophic structure in relation to LLJFL by using
      stable isotope analysis of carbon (delta(13) C) and nitrogen (delta(15) N). The
      delta(15) N values for I. platypterus ranged from 7.51 to 14.190/00 (mean +/-
      s.d. = 12.06 +/- 1.160/00) and the delta(13) C values ranged from -22.04 to 
      15.480/00 (mean +/- s.d. = -17.62 +/- 1.100/00). The delta(15) N values were
      positively dependent on LLJFL (r(2)  = 0.377), whereas delta(13) C were
      negatively dependent on LLJFL (r(2)  = 0.063). There were significantly different
      seasonal changes in nitrogen and carbon isotopic concentration, but no
      significant differences in concentrations between eastern Taiwan and the South
      China Sea were reported. The trophic level (TL ) of each LLJFL class was
      correlated, starting from 2.84 TL for size class I (LLJFL  < 140 cm) and reaching
      5.03 TL for size class VI (LLJFL > 221 cm). The mean +/- s.d. TL was 4.43 +/-
      0.19 for all samples. The results reveal that I. platypterus occupies a wide
      range of trophic levels and different size classes occupy different trophic
      positions in the pelagic ecosystem. 

PMID- 24447323
TI  - Right atrial appendage aneurysm: a systematic review.
AB  - BACKGROUND: Right atrial appendage aneurysm (RAAA) is rare with fewer than 20
      cases reported in the literature. We sought to systematically review the
      published cases of RAAA in terms of demographics, clinical characteristics,
      treatment, complications, and outcome. METHODOLOGY: Electronic search for case
      reports, case series, and related articles published until July 2013 was carried
      out and clinical data were extracted and analyzed. RESULTS: Seventeen cases of
      RAAA were identified with equal sex distribution and commonly presenting in the
      third decades of life. Dyspnea and palpitation were the most common clinical
      presentations. Echocardiography was the most common diagnostic modality. The mean
      size of aneurysm was 8.83 +/- 4.84 * 6.05 +/- 2.99 cm. Most of the patients were
      treated medically with close follow-up. The mean follow-up period was 10 months.
      Atrial tachyarrhythmias and heart failure were the most common complications.
      CONCLUSION: Right atrial appendage aneurysm although rare may be associated with
      significant morbidity. Surgical resection is indicated in symptomatic patients.

PMID- 24447324
TI  - Force of removal for untunnelled, tunnelled and double-tunnelled peripheral nerve
      catheters.
AB  - We compared the force of extraction for peripheral nerve catheters under three
      different situations in a porcine model using untunnelled, tunnelled and double
      tunnelled catheters. Following insertion of the catheter into the porcine model,
      the catheters were either left untunnelled or a single or double tunnel was
      created for the catheter. The force required to displace the catheter by one
      centimetre was then measured in each of the three groups. The mean (SD) force
      required for displacement of the catheter was 0.23 (0.06) N for the untunnelled
      catheters, 1.16 (0.51) N for the single-tunnelled catheters, and 4.00 (1.70) N
      for the double-tunnelled catheters (p < 0.0001). Tunnelling a peripheral nerve
      catheter leads to a significant increase in the force required for dislodgement.
      This is increased further by introducing a second tunnel. 

PMID- 24447325
TI  - Chemical constituents of Rhododendron formosanum show pronounced growth
      inhibitory effect on non-small-cell lung carcinoma cells.
AB  - The aim of the present study was to investigate whether Rhododendron formosanum
      Hemsl. (Ericaceae), an endemic species in Taiwan, exhibits antineoplastic
      potential against non-small-cell lung carcinoma (NSCLC). R. formosanum was
      successively extracted with methanol and then separated into dichloromethane (RFL
      DCM), ethyl acetate (RFL-EA), n-butanol (RFL-BuOH), and water (RFL-H2O)
      fractions. Among these extracts, RFL-EA exhibited the most effective
      antineoplastic effect. This study also demonstrated that fractions 2 and 3 from
      the RFL-EA extract (RFL-EA-2, RFL-EA-3) possessed the strongest antineoplastic
      potential against NSCLC cells. The major phytochemical constituents of RFL-EA-2
      and RFL-EA-3 were ursolic acid, oleanolic acid, and betulinic acid. This study
      indicated that ursolic acid demonstrated the most efficient antineoplastic
      effects on NSCLC cells. Ursolic acid inhibited growth of NSCLC cells in a dose-
      and time-dependent manner and stimulated apoptosis. Apoptosis was substantiated
      by activation of caspase-3 and -9, and a decrease in Bcl-2 and an elevation of
      the Bax were also observed following ursolic acid treatment. Ursolic acid
      activated AMP-activated protein kinase (AMPK) and then inhibited the mammalian
      target of rapamycin (mTOR), which controls protein synthesis and cell growth.
      Moreover, ursolic acid decreased the expression and/or activity of lipogenic
      enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) via
      AMPK activation. Collectively, these data provide insight into the chemical
      constituents and anticancer activity of R. formosanum against NSCLC cells, which
      are worthy of continued study. 

PMID- 24447326
TI  - High prevalence of Chlamydophila psittaci subclinical infection in Italian
      patients with Sjogren's syndrome and parotid gland marginal zone B-cell lymphoma
      of MALT-type.
AB  - OBJECTIVES: To assess Chlamydophila psittaci (Cp) subclinical infection in
      patients with Sjogren's syndrome (SS). METHODS: Seventy-four SS patients (55.4 +/
      13.4 yrs; 94.6% females) were studied. Among them, 18 had salivary gland mucosa
      associated lymphoid tissue (MALT) B-cell lymphoma, 20 myoepithelial sialoadenitis
      (MESA), and 36 no lymphoproliferative disorders (LPD). The presence of Cp DNA was
      assessed in peripheral blood of all patients by specific PCR protocols. Paired
      salivary gland samples were also investigated whenever available (34 cases),
      including lymphomatous and non-lymphomatous samples, as well as major and minor
      salivary gland tissues. As controls, 225 blood donors were analysed in the
      peripheral blood. RESULTS: Overall, Cp DNA was detected in 11/74 (14.9%) SS
      patients vs. 1/225 (0.4%) controls (p<0.0001). Cp was detected at higher
      frequency in MALT lymphoma patients (6/18, 33.3%), as compared with MESA (3/20,
      15%) or patients without LPD (2/36, 5.6%), (MALT lymphomas vs. others: p=0.02). A
      similar Cp prevalence was observed in blood vs. salivary gland tissues, however
      with a higher frequency in the major than in the minor salivary glands (5/18,
      27.8%, vs. 1/17, 5.9%, p=0.18). Cp-positive patients were all rheumatoid factor
      positive (11/11, 100% vs. 40/63, 63.5% Cp-negative; p=0.014), while no difference
      was noticed for anti-SSA/SSB positivity. CONCLUSIONS: In the light of accepted
      models of MALT B-cell lymphomagenesis and considering previous data implicating
      Cp infection in ocular adnexa MALT lymphoma, our results suggest that Cp
      infection could be involved also in a fraction of patients with SS developing
      lymphoma. The potential therapeutic implications of these findings appear
      worthwhile.

PMID- 24447328
TI  - Is 2014 the year of the wound?

PMID- 24447331
TI  - Mitochondrial DNA variation and increased oxidative damage in euthymic patients
      with bipolar disorder.
AB  - AIM: The aim of this study was to compare alterations of mitochondrial DNA
      (mtDNA) copy number, single nucleotide polymorphisms, and oxidative damage of
      mtDNA in clinically stable patients with bipolar I disorder (BD). METHODS:
      Patients meeting DSM-IV diagnostic criteria for BD were recruited from the
      psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were
      clinically stable and their medications had not changed for at least the
      preceding 2 months. Exclusion criteria were substance-induced psychotic disorder,
      eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects
      did not have any history of major psychiatric disorders and they were non
      smokers. By analyzing peripheral blood leukocytes, copy number, single nucleotide
      polymorphisms and oxidative damage of mtDNA were compared between the two groups.
      RESULTS: The median age of the subjects was 38 years and 41.5 years in the
      comparison and BD groups, respectively. The leukocyte mtDNA copy number of the BD
      group was significantly lower than that of the comparison group (P < 0.001). BD
      patients had significantly higher mitochondrial oxidative damage than the
      comparison group (6.1 vs 3.9, P < 0.001). After generalized linear model
      adjusting with age, sex, smoking, family history, and psychotropic use, mtDNA
      copy number was still significantly lower in the BD group (P < 0.001). MtDNA
      oxidative damage was positively correlated with age (P = 0.034), although mtDNA
      oxidative damage was similar between these two groups. CONCLUSION: Possible
      involvement of oxidative stress and mitochondria in the pathophysiology of BD
      needs more large-scale studies. It is important that psychiatrists retain a high
      level of suspicion for mitochondrial dysfunction in patients with bipolar
      disorder.

PMID- 24447332
TI  - MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City
      firefighters.
AB  - RATIONALE: After 9/11/2001, most FDNY workers had persistent lung function
      decline but some exposed workers recovered. We hypothesized that the
      protease/anti-protease balance in serum soon after exposure predicts subsequent
      recovery. METHODS: We performed a nested case-control study measuring biomarkers
      in serum drawn before 3/2002 and subsequent forced expiratory volume at one
      second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix
      metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of
      metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte
      distribution and a concentration above 75th percentile defined elevated biomarker
      expression. An FEV1 one standard deviation above the mean defined resistance to
      airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and
      exposure intensity modeled the association between elevated biomarker expression
      and above average FEV1. RESULTS: FEV1 in cases and controls declined 10% of after
      9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while
      decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of
      resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.
      CONCLUSIONS: Resistant cases displayed healing, returning to 99% of pre-exposure
      values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects
      independent pathways to airway injury and repair after WTC exposure.

PMID- 24447333
TI  - Kinome and mRNA expression profiling of high-grade osteosarcoma cell lines
      implies Akt signaling as possible target for therapy.
AB  - BACKGROUND: High-grade osteosarcoma is a primary malignant bone tumor mostly
      occurring in adolescents and young adults, with a second peak at middle age.
      Overall survival is approximately 60%, and has not significantly increased since
      the introduction of neoadjuvant chemotherapy in the 1970s. The genomic profile of
      high-grade osteosarcoma is complex and heterogeneous. Integration of different
      types of genome-wide data may be advantageous in extracting relevant information
      from the large number of aberrations detected in this tumor. METHODS: We analyzed
      genome-wide gene expression data of osteosarcoma cell lines and integrated these
      data with a kinome screen. Data were analyzed in statistical language R, using
      LIMMA for detection of differential expression/phosphorylation. We subsequently
      used Ingenuity Pathways Analysis to determine deregulated pathways in both data
      types. RESULTS: Gene set enrichment indicated that pathways important in genomic
      stability are highly deregulated in these tumors, with many genes showing
      upregulation, which could be used as a prognostic marker, and with kinases
      phosphorylating peptides in these pathways. Akt and AMPK signaling were
      identified as active and inactive, respectively. As these pathways have an
      opposite role on mTORC1 signaling, we set out to inhibit Akt kinases with the
      allosteric Akt inhibitor MK-2206. This resulted in inhibition of proliferation of
      osteosarcoma cell lines U-2 OS and HOS, but not of 143B, which harbors a KRAS
      oncogenic transformation. CONCLUSIONS: We identified both overexpression and
      hyperphosphorylation in pathways playing a role in genomic stability. Kinome
      profiling identified active Akt signaling, which could inhibit proliferation in
      2/3 osteosarcoma cell lines. Inhibition of PI3K/Akt/mTORC1 signaling may be
      effective in osteosarcoma, but further studies are required to determine whether
      this pathway is active in a substantial subgroup of this heterogeneous tumor.

PMID- 24447334
TI  - Rift Valley fever outbreak, southern Mauritania, 2012.
AB  - After a period of heavy rainfall, an outbreak of Rift Valley fever occurred in
      southern Mauritania during September-November 2012. A total of 41 human cases
      were confirmed, including 13 deaths, and 12 Rift Valley fever virus strains were
      isolated. Moudjeria and Temchecket Departments were the most affected areas. 

PMID- 24447335
TI  - Predictors of uropathogens other than Escherichia coli in patients with community
      onset acute pyelonephritis.
AB  - AIM: A constant reduction in the incidence of community-onset acute
      pyelonephritis (CO-APN) caused by Escherichia coli has been shown with a parallel
      increase incidence caused by other organisms. Therefore, we evaluated the risk
      factors and outcome of non-E. coli as uropathogens in patients with community
      onset APN. METHODS: As a part of a nationwide multicentre surveillance study
      conducted in Korea, a total of 416 patients with CO-APN were collected with their
      epidemiological, antibiotic treatment and outcome data. RESULTS: The risk factors
      and outcomes of non-E. coli as uropathogens were evaluated in a total of 416
      patients with culture-confirmed CO-APN. Non-E. coli caused 127 cases (30.5%) of
      CO-APN. CO-APN caused by non-E. coli resulted in higher inappropriate empirical
      therapy (38.6% vs. 20.1%, p < 0.001), longer hospital stay (12.6 days vs. 6.7
      days, p = 0.005) and higher 30-day mortality (9.4% vs. 3.8% p = 0.020) compared
      with CO-APN caused by E. coli. Multivariate analyses showed that male gender (OR,
      3.48; CI, 2.13-5.67; p < 0.001), underlying haematological disease (OR, 5.32; CI,
      1.17-24.254; p = 0.031), underlying benign prostate hyperplasia (OR, 2.61; CI,
      1.02-6.74; p = 0.046), chronic indwelling urethral catheter (OR, 6.34; CI, 1.26
      31.84; p = 0.025) and admission history in the previous 6 months (OR, 2.12; CI,
      1.23-3.58; p = 0.005) were predictors for CO-APN caused by a non-E. coli isolate.
      CONCLUSIONS: Community-onset APN caused by non-E. coli represents a distinct
      subset of urinary tract infections with worse outcomes. The defined risk factors
      related with non-E. coli should be taken into consideration when empirical
      antibiotic therapy is prescribed in patients with community-onset APN.

PMID- 24447336
TI  - A case study of a real-time evaluation of the risk of disease transmission
      associated with a failure to follow recommended sterilization procedures.
AB  - BACKGROUND: Failures to follow recommendations for reprocessing of surgical
      instruments may place patients at risk for exposure to pathogenic microorganisms.
      When such failures occur, medical facilities often face considerable uncertainty
      and challenges in assessing the actual risks of disease transmission. METHODS: In
      2011, staff at an Ohio hospital determined that surgical instruments inside a
      Steriset Container had inadvertently been autoclaved on a gravity cycle rather
      than on the recommended pre-vacuum cycle, potentially exposing 72 patients who
      underwent surgery with the instruments to risk of infection. To provide an
      assessment of the level of risk, we tested the effectiveness of the machine
      washer/disinfector step and of the sterilization process inside the Steriset
      Container on the gravity cycle for killing of Geobacillus stearothermophilus
      spores, Clostridium difficile spores, and methicillin-resistant Staphylococcus
      aureus (MRSA). Based on the test results, the risk of transmission of MRSA by the
      instruments was calculated and the risk of transmission of hepatitis B virus was
      estimated. RESULTS: The machine washer/disinfector consistently reduced MRSA
      recovery by a factor of 1:100,000. The sterilization process inside the Steriset
      Container consistently reduced MRSA concentrations by a factor of >1:10,000,000
      and killed 105C. difficile spores and 105G. stearothermophilus spores. The risk
      of MRSA transmission due to the incident was calculated to be 1 in 100 trillion.
      CONCLUSIONS: The risk for transmission of infection due to the failure to follow
      recommended sterilization processes was negligible based upon complete killing of
      G. stearothermophilus biological indicator spores, C. difficile spores, and MRSA
      under conditions that replicated the incident where proper procedures were not
      followed. Such real-time assessments of the risks associated with specific
      incidents may provide evidence-based information that can be used to inform
      decisions regarding disclosure of the incident to patients.

PMID- 24447338
TI  - The phosphorylation of HIV-1 Gag by atypical protein kinase C facilitates viral
      infectivity by promoting Vpr incorporation into virions.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) Gag is the main
      structural protein that mediates the assembly and release of virus-like particles
      (VLPs) from an infected cell membrane. The Gag C-terminal p6 domain contains
      short sequence motifs that facilitate virus release from the plasma membrane and
      mediate incorporation of the viral Vpr protein. Gag p6 has also been found to be
      phosphorylated during HIV-1 infection and this event may affect virus
      replication. However, the kinase that directs the phosphorylation of Gag p6
      toward virus replication remains to be identified. In our present study, we
      identified this kinase using a proteomic approach and further delineate its role
      in HIV-1 replication. RESULTS: A proteomic approach was designed to
      systematically identify human protein kinases that potently interact with HIV-1
      Gag and successfully identified 22 candidates. Among this panel, atypical protein
      kinase C (aPKC) was found to phosphorylate HIV-1 Gag p6. Subsequent LC-MS/MS and
      immunoblotting analysis with a phospho-specific antibody confirmed both in vitro
      and in vivo that aPKC phosphorylates HIV-1 Gag at Ser487. Computer-assisted
      structural modeling and a subsequent cell-based assay revealed that this
      phosphorylation event is necessary for the interaction between Gag and Vpr and
      results in the incorporation of Vpr into virions. Moreover, the inhibition of
      aPKC activity reduced the Vpr levels in virions and impaired HIV-1 infectivity of
      human primary macrophages. CONCLUSION: Our current results indicate for the first
      time that HIV-1 Gag phosphorylation on Ser487 is mediated by aPKC and that this
      kinase may regulate the incorporation of Vpr into HIV-1 virions and thereby
      supports virus infectivity. Furthermore, aPKC inhibition efficiently suppresses
      HIV-1 infectivity in macrophages. aPKC may therefore be an intriguing therapeutic
      target for HIV-1 infection.

PMID- 24447340
TI  - Dynamics of follicular growth and progesterone concentrations in cyclic and
      anestrous suckling Nelore cows (Bos indicus) treated with progesterone, equine
      chorionic gonadotropin, or temporary calf removal.
AB  - The objective of this study was to investigate the effects of eCG and temporary
      calf removal (TCR) associated with progesterone (P4) treatment on the dynamics of
      follicular growth, CL size, and P4 concentrations in cyclic (n = 36) and
      anestrous (n = 30) Nelore cows. Cyclic (C) and anestrous (A) cows were divided
      into three groups. The control group received 2 mg of estradiol benzoate via
      intramuscular (IM) injection and an intravaginal device containing 1.9 g of P4 on
      Day 0. On Day 8, the device was removed, and the animals received 12.5 mg of
      dinoprost tromethamine IM. After 24 hours, the animals received 1 mg of estradiol
      benzoate IM. In the eCG group, cows received the same treatment described for the
      control group but also received 400 UI of eCG at the time of device removal. In
      the TCR group, calves were separated from the cows for 56 hours after device
      removal. Ultrasound exams were performed every 24 hours after device removal
      until the time of ovulation and 12 days after ovulation to measure the size of
      the CL. On the same day as the CL measurement, blood was collected to determine
      the plasma P4 level. Statistical analyses were performed with a significance
      level of P <= 0.05. In cyclic cows, the presence of the CL at the beginning of
      protocol resulted in a smaller follicle diameter at the time of device removal
      (7.4 +/- 0.3 mm in cows with CL vs. 8.9 +/- 0.4 mm in cows without CL; P = 0.03).
      All cows ovulated within 72 hours after device removal. Anestrous cows treated
      with eCG or TCR showed follicle diameter at fixed-timed artificial insemination
      (A-eCG 10.2 +/- 0.3 and A-TCR 10.3 +/- 0.5 mm) and follicular growth rate (A-eCG
      1.5 +/- 0.2 and A-TCR 1.3 +/- 0.1 mm/day) similar to cyclic cows (C-eCG 11.0 +/-
      0.6 and C-TCR 12.0 +/- 0.5 mm) and (C-eCG 1.4 +/- 0.2 and C-TCR 1.6 +/- 0.2
      mm/day, respectively; P <= 0.05). Despite the similarities in CL size, the
      average P4 concentration was higher in the A-TCR (9.6 +/- 1.4 ng/mL) than in the
      A-control (4.0 +/- 1.0 ng/mL) and C-TCR (4.4 +/- 1.0 ng/mL) groups (P < 0.05).
      From these results, we conclude that eCG treatment and TCR improved the fertility
      of anestrous cows by providing follicular growth rates and size of dominant
      follicles similar to cyclic cows. Additionally, TCR increases the plasma
      concentrations of P4 in anestrous cows. 

PMID- 24447339
TI  - PMA synergistically enhances apicularen A-induced cytotoxicity by disrupting
      microtubule networks in HeLa cells.
AB  - BACKGROUND: Combination therapy is key to improving cancer treatment efficacy.
      Phorbol 12-myristate 13-acetate (PMA), a well-known PKC activator, increases the
      cytotoxicity of several anticancer drugs. Apicularen A induces cytotoxicity in
      tumor cells through disrupting microtubule networks by tubulin down-regulation.
      In this study, we examined whether PMA increases apicularen A-induced
      cytotoxicity in HeLa cells. METHODS: Cell viability was examined by thiazolyl
      blue tetrazolium (MTT) assays. To investigate apoptotic potential of apicularen
      A, DNA fragmentation assays were performed followed by extracting genomic DNA,
      and caspase-3 activity assays were performed by fluorescence assays using
      fluorogenic substrate. The cell cycle distribution induced by combination with
      PMA and apicularen A was examined by flow cytometry after staining with propidium
      iodide (PI). The expression levels of target proteins were measured by Western
      blotting analysis using specific antibodies, and alpha-tubulin mRNA levels were
      assessed by reverse transcription polymerase chain reaction (RT-PCR). To examine
      the effect of combination of PMA and apicularen A on the microtubule
      architecture, alpha-tubulin protein and nuclei were visualized by
      immunofluorescence staining using an anti-alpha-tubulin antibody and PI,
      respectively. RESULTS: We found that apicularen A induced caspase-dependent
      apoptosis in HeLa cells. PMA synergistically increased cytotoxicity and apoptotic
      sub-G1 population induced by apicularen A. These effects were completely blocked
      by the PKC inhibitors Ro31-8220 and Go6983, while caspase inhibition by Z-VAD-fmk
      did not prevent cytotoxicity. RNA interference using siRNA against PKCalpha, but
      not PKCbeta and PKCgamma, inhibited cytotoxicity induced by combination PMA and
      apicularen A. PMA increased the apicularen A-induced disruption of microtubule
      networks by further decreasing alpha- and beta-tubulin protein levels in a PKC
      dependent manner. CONCLUSIONS: These results suggest that the synergy between PMA
      and apicularen A is involved by PKCalpha activation and microtubule disruption,
      and that may inform the development of novel approaches to treat cancer.

PMID- 24447341
TI  - Occurrence of invasive cancer after endoscopic treatment of Barrett's esophagus
      with high-grade dysplasia and intramucosal cancer in physiologically fit
      patients: time for a review of surveillance and treatment guidelines.

PMID- 24447342
TI  - Age- and sex-related emotional and behavioral problems in children with autism
      spectrum disorders: comparison with control children.
AB  - AIM: Children with autism spectrum disorders (ASD) often present with emotional
      and behavioral problems, which could change the clinical course, especially
      during childhood, and affect future quality of life. The aim of this study was to
      clarify the age- and sex-related differences of these problems in ASD. METHODS:
      The study subjects were 173 patients with ASD (age: 4-16 years) and 173 age- and
      sex-matched community children (control group). The parent version of the
      Strengths and Difficulties Questionnaire was used for comparison of the emotional
      and behavioral problems between the two groups. RESULTS: The Strengths and
      Difficulties Questionnaire scores were significantly higher in children with ASD
      than controls at all ages. The score of total difficulties was significantly
      higher in girls with ASD than in boys, while the score in male controls was
      significantly higher than in female controls. Age-related differences in
      emotional and behavioral problems were observed both in children with ASD and
      controls, but the characteristics were different: in children with ASD, emotional
      symptoms and peer problems in both sexes and conduct problems in girls increased
      significantly with age, while none of the problems in the controls changed with
      age except for a decrease in the score of hyperactivity/inattention
      developmentally in both sexes. Prosocial behaviors of children with ASD and
      controls showed small changes with age. CONCLUSION: Emotional and behavioral
      problems are common in children with ASD and showed age- and sex-related
      differences. Our study emphasizes the importance of recognizing those differences
      among children with ASD for early intervention.

PMID- 24447343
TI  - Neutrophil-to-lymphocyte ratio may predict subclinical atherosclerosis in
      patients with psoriasis.
AB  - BACKGROUND: Systemic inflammation beyond the skin may provide an explanation of
      the increased cardiovascular risk observed in psoriasis. It was hypothesized that
      neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are
      potential predictors of subclinical atherosclerosis measured by aortic velocity
      propagation (AVP) and carotid intima-media thickness (CIMT) in psoriasis.
      METHODS: Fifty-one patients with psoriasis taking no antipsoriatic therapy and 37
      age- and sex-matched healthy controls were prospectively enrolled. The Psoriasis
      Area and Severity Index (PASI) was calculated. Complete blood counts were
      obtained. Measurements of AVP and CIMT were performed. RESULTS: The baseline
      clinical and demographic features, and white blood cell, platelet, neutrophil,
      lymphocyte, monocyte, and PLR were similar in both groups. NLR and high
      sensitivity C-reactive protein (hs-CRP) were higher in the psoriasis group than
      the control group (P = 0.001, P < 0.001; respectively). The psoriasis group had
      lower AVP and higher CIMT values than those of controls (AVP: 48.9 +/- 18.1 vs.
      64.3 +/- 14.5 cm/sec; P < 0.001, CIMT: 0.84 +/- 0.29 vs. 0.63 +/- 0.27 mm; P =
      0.001, respectively). PASI was positively correlated with NLR and hs-CRP (r =
      0.423, P = 0.002; r = 0.315, P = 0.024, respectively). There was an inverse
      association between AVP and CIMT (r = -0.749, P < 0.001). Binary logistic
      regression analysis demonstrated that NLR was the only variable able to predict
      lower AVP (<=41 cm/sec) and higher CIMT (>0.9 mm) values (P = 0.024 and 0.023;
      respectively). CONCLUSION: NLR is potentially an unrecognized predictor of
      subclinical atherosclerosis in patients with psoriasis. Future studies assessing
      the prognostic significance of NLR on cardiovascular event rates in psoriasis
      patients would be of great interest.

PMID- 24447344
TI  - Prevalence of neurological conditions across the continuum of care based on
      interRAI assessments.
AB  - BACKGROUND: Although multiple studies have estimated the prevalence of
      neurological conditions in the general Canadian population, limited research
      exists regarding the proportion affected with these conditions in non-acute
      health care settings in Canada. Data from standardized clinical assessments based
      on the interRAI suite of instruments were used to estimate the prevalence of
      eight neurological conditions across the continuum of care including Alzheimer's
      disease, Parkinson's disease, epilepsy, traumatic brain injury, multiple
      sclerosis, cerebral palsy, Huntington's disease, and amyotrophic lateral
      sclerosis. METHODS: Cohorts of individuals receiving care in nursing homes
      (N=103,820), home care (N=91,021), complex continuing care (N=10,581), and
      psychiatric hospitals (N=23,119) in Canada were drawn based on their most recent
      interRAI assessment within each sector for a six-month period in 2010. These data
      were linked to the Discharge Abstract Database and National Ambulatory Care
      Reporting System data sets to develop five different case definition scenarios
      for estimating prevalence. RESULTS: The conditions with the highest estimated
      prevalences in these care settings in Canada were Alzheimer's disease and related
      dementias, Parkinson's disease, epilepsy, and traumatic brain injury. However,
      there were notable cross-sector differences in the prevalence of each condition,
      and regional variations. Prevalence estimates based on acute hospital
      administrative data alone were substantially lower for all conditions evaluated.
      CONCLUSIONS: The proportion of persons with neurological conditions in non-acute
      health care settings in Canada is substantially higher than is generally reported
      for the general population. It is essential for these care settings to have the
      expertise and resources to respond effectively to the strengths, preferences, and
      needs of the growing population of persons with neurological conditions. The use
      of hospital or emergency department records alone is likely to substantially
      underestimate the true prevalence of neurological conditions across the continuum
      of care. However, interRAI assessment records provide a helpful source of
      information for obtaining these estimates in nursing home, home care, and mental
      health settings.

PMID- 24447345
TI  - Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer
      development.
AB  - IL-6 signaling is of central importance for the maintenance of chronic intestinal
      inflammation in inflammatory bowel diseases (IBD) such as Crohn's disease and
      ulcerative colitis. IL-6 regulates T cell differentiation, activation and
      resistance against apoptosis and thereby controls the balance between pro
      inflammatory T cell subsets such as Th1 or Th17 cells and immunosuppressive
      regulatory T cells. Furthermore, IL-6 has been implicated in the pathogenesis of
      colorectal cancer (CRC). In fact, IL-6 directly promotes tumor cell proliferation
      and survival through STAT3 activation. Due to its role in both types of diseases,
      IL-6 has been proposed as a missing link between inflammation and tumor
      development. During recent years, several therapeutics targeting IL-6 dependent
      pathways have been developed. Although clinical data about anti-IL-6 treatment in
      intestinal diseases are currently scarce, targeting this pathway might be a
      promising strategy in IBD and CRC. 

PMID- 24447346
TI  - Microbial diversity in fecal samples depends on DNA extraction method: easyMag
      DNA extraction compared to QIAamp DNA stool mini kit extraction.
AB  - BACKGROUND: There are challenges, when extracting bacterial DNA from specimens
      for molecular diagnostics, since fecal samples also contain DNA from human cells
      and many different substances derived from food, cell residues and medication
      that can inhibit downstream PCR. The purpose of the study was to evaluate two
      different DNA extraction methods in order to choose the most efficient method for
      studying intestinal bacterial diversity using Denaturing Gradient Gel
      Electrophoresis (DGGE). FINDINGS: In this study, a semi-automatic DNA extraction
      system (easyMag(r), BioMerieux, Marcy I'Etoile, France) and a manual one (QIAamp
      DNA Stool Mini Kit, Qiagen, Hilden, Germany) were tested on stool samples
      collected from 3 patients with Inflammatory Bowel disease (IBD) and 5 healthy
      individuals. DNA extracts obtained by the QIAamp DNA Stool Mini Kit yield a
      higher amount of DNA compared to DNA extracts obtained by easyMag(r) from the
      same fecal samples. Furthermore, DNA extracts obtained using easyMag(r) seemed to
      contain inhibitory compounds, since in order to perform a successful PCR
      analysis, the sample should be diluted at least 10 times. DGGE performed on PCR
      from DNA extracted by QIAamp DNA Stool Mini Kit DNA was very successful.
      CONCLUSION: QIAamp DNA Stool Mini Kit DNA extracts are optimal for DGGE runs and
      this extraction method yields a higher amount of DNA compared to easyMag(r).

PMID- 24447347
TI  - Congenital unilateral maxillomandibular fusion.

PMID- 24447350
TI  - [Examination and knowledge seeking: the first obligatory course for medical
      students].

PMID- 24447348
TI  - Folic acid pathway single nucleotide polymorphisms associated with methotrexate
      significant adverse events in United States veterans with rheumatoid arthritis.
AB  - OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of
      rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms
      (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase
      [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase
      [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients
      (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were
      genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503,
      rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR
      (rs1801131, rs1801133). AE were abstracted from the medical record using a
      structured instrument. SigAE were defined as an AE leading to MTX
      discontinuation. Covariates included: age, gender, race, RA antibody status,
      tobacco, RA disease duration between diagnosis and MTX course, Charlson-Deyo
      comorbidity index, glucocorticoids, use of prior RA medications, and mean 4
      variable disease activity score. Cox regression was performed to determine
      factors associated with time-to-SigAE. A p-value <= 0.005 established
      significance in the final model. RESULTS: The presence of >= 1 copy of the minor
      allele in MTHFR rs1801131 was associated with an increased hazard ratio (HR) of
      SigAE (HR 3.05, 95% CI 1.48-6.29, p-value 0.003 and HR 3.88, 95% CI 1.62-9.28, p
      value 0.002 for heterozygotes and homozygotes for the minor allele,
      respectively). An interaction term, between FPGS rs7033913 heterozygotes and GGH
      rs11988534 homozygotes for the minor allele, had a p-value <0.0001. CONCLUSIONS:
      RA subjects taking MTX may have decreased time-to-SigAE with >= 1 copy of the
      minor allele in MTHFR rs1801131. Further investigation is warranted, as these
      SNPs may indicate susceptibility to MTX toxicity.

PMID- 24447351
TI  - [Role of caveolin-1 in pulmonary microvascular endothelial cells injury induced
      by lipopolysaccharide in rat].
AB  - OBJECTIVE: To investigate the role of caveolin-1 (Cav-1) in the modulation of rat
      pulmonary microvascular endothelial cells (RPMVEC) injury induced by
      lipopolysaccharide (LPS). METHODS: Cultured RPMVEC were randomly divided into
      time-dependent injury group induced by LPS and intervention group in which cells
      were pretreated by protein kinase A inhibitor (PKI). In the time-dependent injury
      group, monolayers of cells were constructed to determine permeability changes
      after 10 MUg/mL LPS challenge for 0, 1, 3, 6, 12 and 24 hours with the method of
      Evans blue-labeled albumin flux across the monolayer (Pd). Western blotting was
      used to determine the Cav-1 expression after LPS stimulation and the
      phosphorylation-Cav-1 (p-Cav-1) expression after LPS challenge for 0, 10, 30, 60,
      90, 120 minutes. In the intervention group, after pre-treatment with 10 MUmol/L
      PKI for 30 minutes, RPMVECs were challenged with 10 MUg/mL LPS, and the
      expression of p-Cav-1 was determined 30 minutes after LPS challenge, the
      permeability and the Cav-1 protein expression were assessed by Pd and Western
      blotting, respectively. Non-stimulation group and single PKI simulation group
      served as controls. RESULTS: Western blotting revealed that the expression of Cav
      1 protein was elevated at 1 hour (2.97 +/- 0.07), peaking at 3 hours (3.77 +/-
      0.37), then it lowered gradually, but it was still higher at 24 hours (1.45 +/-
      0.18) when compared with 0 hour group (1.12+/-0.08) with significant differences
      (F=178.047, P=0.000). After RPMVEC monolayers were challenged by LPS for
      different periods (0, 1, 3, 6, 12 and 24 hours), there were significant increases
      in a time-dependent manner in Cav-1 expression in the permeability as measured by
      Pd [(99.67 +/- 4.32)%, (118.17 +/- 2.32)%, (159.00 +/- 2.61)%, (141.17 +/-
      2.64)%, (120.17 +/- 2.79)% and (108.83 +/- 2.04)%, F=345.869, P=0.000] which was
      similar to the changes in Cav-1 expression. LPS also increased Cav-1
      phosphorylation in a time-dependent manner occurring at 10 minutes (2.41 +/-
      0.11), peaking at 30 minutes (2.83 +/- 0.10), and then it decreased gradually,
      finally returned to basal levels (1.03+/-0.04) at 120 minutes (1.04 +/- 0.04)
      after LPS treatment with significant difference (F=519.417, P=0.000). When PKI
      was pre-treated with RPMVEC the expression of Cav-1 was significantly increased
      (5.07 +/- 0.22 vs. 3.81 +/- 0.23, P<0.01), and p-Cav-1 (3.93 +/- 0.23 vs. 2.77+/
      0.10, P<0.01), and RPMVEC monolayers permeability was enhanced [(184.17 +/-
      5.49)% vs. (151.50 +/- 3.08)%, P<0.01] after being challenged. CONCLUSIONS: Up
      regulated expression of Cav-1 and phosphorylation-Cav-1 that may be modulated by
      protein kinase A signal pathway plays an important role in RPMVEC permeability
      injury as induced by LPS.

PMID- 24447352
TI  - [Relationship between early coagulability parameters at admission and outcome in
      patients with severe heatstroke].
AB  - OBJECTIVE: To discuss the relationship between early coagulability parameters at
      admission in patients with severe heatstroke and their outcome. METHODS: The data
      from 176 patients with severe heatstroke admitted to Guangzhou General Hospital
      of Guangzhou Military Command from January 1st, 2002 to August 31st, 2013 were
      retrospectively analyzed. The patients were divided into survival group (n=150)
      and non-survival group (n=26) according to the outcome. The incipient values of
      coagulability function indexes within 24 hours after admission were collected,
      and prothrombin time (PT), activated partial thromboplastin time (APTT) and
      platelet count (PLT) were compared between two groups to assess the statistically
      significant indexes for the analysis of the relationship between coagulability
      parameters and outcome with receiver operator characteristic curve (ROC curve).
      RESULTS: Compared with those in survival group, PT and APTT were significantly
      prolonged in non-survival group [PT: 34.0 (18.8, 45.6) s vs. 18.4 (13.8, 18.0) s,
      Z=-6.09, P=0.000; APTT: 79.7 (41.0, 91.2) s vs. 60.8 (33.4, 41.0) s, Z=-5.08,
      P=0.000]. The PLT counts were significantly lower in the non-survival group than
      those in survival group [ 60.8(4.7, 95.3) * 109/L vs. 128.4(79.8, 180.8) * 109/L,
      Z=-4.34, P=0.000]. ROC curve analysis showed that the area under ROC curve (AUC)
      for PT in predicting the death of patients with severe heatstroke was 0.874, with
      standard error of 0.028 and 95% confidence interval (95%CI) of 0.819-0.927
      (P=0.000). The best cut-off was 18.5 s, with sensitivity of 76.9% and specificity
      of 20.0%. AUC for APTT in predicting the death of patients with severe heatstroke
      was 0.812, with standard error of 0.047 and 95%CI of 0.740-0.903 (P=0.000). The
      best cut-off was 46.55 s, with sensitivity of 69.2% and specificity of 14.0%. AUC
      for PLT in predicting the death of patients with severe heatstroke was 0.767,
      with standard error of 0.040 and 95%CI of 0.688-0.845 (P=0.000). The best cut-off
      was 86.5 * 109/L, with sensitivity of 68.0% and specificity of 36.8%.
      CONCLUSIONS: Early prolonged PT and APTT and reduced PLT count are associated
      with increased risk of death, and it can predict a poor outcome in patients with
      severe heatstroke.

PMID- 24447353
TI  - [Value of a model based on PIRO conception in predicting the prognosis in
      critical patients].
AB  - OBJECTIVE: To investigate the values of factors based on PIRO conception in
      predicting the prognosis of critical patients. METHODS: The clinical data of
      critical patients admitted to Hainan Branch of PLA General Hospital from December
      2011 to August 2013 were retrospectively analyzed. The patients were randomly
      divided into non-survivors and survivors groups according to 28-day outcome.
      Predisposition (P), injury (I), response (R) and organ dysfunction induced by
      injury (O) were compared between two groups. The indexes with statistical
      significance (P<0.2) by univariate analysis were included in multivariate
      logistic regression analysis, and the receiver operating characteristic curve
      (ROC curve) was plotted to evaluate the values of factors based on PIRO
      conception in predicting the prognosis of critical patients. RESULTS: One hundred
      and eighty-seven critical patients were enrolled, and among them 75 (40.1%)
      patients died. Univariate analysis showed that the age, underlying disease
      scores, history of cardiovascular disease, diabetes mellitus, and cerebrovascular
      disease, positive blood culture, whether or not complicated with acute
      respiratory distress syndrome (ARDS) or severe sepsis/septic shock, procalcitonin
      (PCT), acute physiology and chronic health evaluation II (APACHE II), acute
      pathophysiology score (APS) and sequential organ failure assessment (SOFA) were
      found to be the factors related with the prognosis (all P<0.2). Multivariate
      logistic regression analysis showed that the underlying disease scores [odds
      ratio (OR)=1.874, 95% confidence interval (95%CI) 1.138-3.084, P=0.014], whether
      patients occurrence of severe sepsis/septic shock (OR=0.167, 95%CI 0.064-0.435,
      P=0.000) and SOFA scores (OR=1.498, 95%CI 1.283-1.750, P=0.000) were independent
      factors for predicting 28-day mortality. The new model combined with above
      factors had more prognostic value in predicting the mortality than a single
      variable. The area under ROC curve (AUC) for PIRO model based on indexes with
      statistical significance by univariate analysis was 0.877 (0.821-0.934), P=0.000.
      AUC for PIRO model based on underlying disease scores, severe sepsis/septic
      shock, SOFA scores was 0.871 (0.814-0.928), P=0.000. AUC for SOFA was 0.762
      (0.687-0.837), P=0.000. AUC for APS was 0.726 (0.647-0.805), P=0.000. AUC for
      underlying disease scores was 0.678 (0.593-0.763), P=0.000. AUC for PCT was 0.636
      (0.548-0.724), P=0.004. AUC for age was 0.618 (0.532-0.705), P=0.013].
      CONCLUSIONS: The multivariate regression analysis based on PIRO system may help
      to predict 28 days mortality in critical patients.

PMID- 24447354
TI  - [The effect of low molecular heparin on the prognosis of severe pneumonia in
      elderly patients].
AB  - OBJECTIVE: To investigate the effect of low molecular heparin on degree of
      severity and prognosis of severe pneumonia in elderly patients. METHODS: A
      prospective randomized control study was conducted. During October 2009 to July
      2013, 63 patients over 65 years old and suffering from severe pneumonia were
      enrolled. Patients were grouped into control or treatment group randomly. The
      control group (n=36) received routine treatment, while low molecular heparin 4 kU
      once a day was added in treatment group (n=39) for 7 days. Acute physiology and
      chronic health evaluationII(APACHEII) score, coagulation function indexes, blood
      gas analysis, arterial lactic acid at 1, 3, 7 days after treatment, and length of
      mechanical ventilation, days of stay in ICU, and 7-day mortality were compared
      between both groups. RESULTS: The basic data and APACHEII score had no difference
      between two groups (all P>0.05). Bleeding events occurred on day 1, 3, 7 in 1, 1,
      2 patients in control group, respectively, and 0, 1, 3 cases in treatment group.
      There was no difference in APACHEII score on day 1 and day 3 between control
      group and treatment group (1 day: 19.33 +/- 5.90 vs. 20.31 +/- 4.97, t=0.775,
      P=0.441; 3 days: 18.69 +/- 4.88 vs. 17.41 +/- 3.83, t=1.272, P=0.207). APACHEII
      score on day 7 in treatment group was significantly lower than that in control
      group (13.92 +/- 3.61 vs. 16.20 +/- 4.23, t=2.480, P=0.016). There was no
      significant difference in coagulation function indexes during observation period
      between two groups (all P>0.05). The blood gas analysis showed that only arterial
      partial pressure of oxygen (PaO2) 7 days after treatment in treatment group was
      significantly higher than that in control group (110.52 +/- 28.57 mm Hg vs. 95.47
      +/- 24.17 mm Hg, t=-2.354, P=0.022). There was no significant difference in 7-day
      mortality between two groups. The mechanical ventilation time in treatment group
      was slightly shorter than that in control group (147.45 +/- 111.45 hours vs.
      192.20 +/- 115.57 hours, t=1.704, P=0.093). The length of stay in ICU in
      treatment group was significantly shorter than that in control group (13.77 +/-
      5.77 days vs. 17.22 +/- 6.21 days, t=2.497, P=0.015). CONCLUSIONS: In elderly
      patients suffering from severe pneumonia, low molecular heparin may reduce
      APACHEII score, shorten mechanical ventilation time and length of ICU stay, and
      the prognosis may be improved.

PMID- 24447355
TI  - [Clinical experience of double plasma molecular absorption with a combination of
      two hemoperfusion machines in treatment of liver failure].
AB  - OBJECTIVE: To evaluate the effect of the double plasma molecular adsorption
      system (DPMAS) with a combination of two hemoperfusion machines in treatment of
      liver failure. METHODS: A retrospective analysis was conducted. The clinical data
      from 42 patients with liver failure admitted to Tianjin Second People's Hospital
      from September 2012 to September 2013 were enrolled. Patients received 166
      courses of blood purification treatment, including 97 courses of plasmapheresis
      (PE) and 69 courses of DPMAS. The DPMAS treatment was performed with a
      combination of two hemoperfusion machines, with one a blood pump and the other a
      plasma pump, for 2-3 hours. Liver function, tumor necrosis factor-alpha (TNF
      alpha), electrolytes and blood routine were determined before and after
      treatment. Adverse reactions were observed and the nursing experiences were
      summarized. RESULTS: The survival rate of 42 liver failure patients was 64.29%,
      and the total bilirubin (TBil), NH3, total bile acid (TBA) and TNF-alpha were
      decreased and the albumin (ALB) was increased after PE and DPMAS. Further
      analysis of the rate of changes after treatment (after treatment/before
      treatment*100%) showed that when compared with that in DPMAS, the TBil and TBA
      were decreased significantly in PE [TBil: (62.21 +/- 5.51)% vs. (64.39 +/-
      4.61)%, t=2.683, P=0.008; TBA: (77.10 +/- 4.44)% vs. (85.91 +/- 6.95)%, t=9.952,
      P=0.000], and the level of ALB was elevated significantly in PE when compared
      with that in DPMAS [(113.12 +/- 2.90)% vs. (101.87 +/- 2.91)%, t=24.602,
      P=0.000]. NH3 and TNF-alpha were decreased in both groups withe no statistical
      significance [NH3: (79.59 +/- 5.72)% vs. (80.56 +/- 7.56)%, t=0.934, P=0.351; TNF
      alpha: (61.66 +/- 4.67)% vs. (62.73 +/- 3.67)%, t=1.638, P=0.108]. The blood
      electrolytes and routine blood test showed that there was no significant change
      before and after treatments in DPMAS group (K+: 3.92 +/- 0.83 mmol/L vs. 3.91 +/-
      0.82 mmol/L, t=0.501, P=0.618; Na+: 136.89 +/- 5.69 mmol/L vs. 136.74 +/- 5.83
      mmol/L, t=1.077, P=0.285; Cl-: 96.58 +/- 3.33 mmol/L vs. 96.55 +/- 3.27 mmol/L,
      t=0.245, P=0.807; white cell count: 5.22 +/- 0.93 * 109/L vs. 5.43 +/- 1.11 *
      109/L, t=1.125, P=0.265; hemoglobin: 110.97 +/- 19.20 g/L vs. 112.69 +/- 19.67
      g/L, t=0.643, P=0.522; platelet count: 105.28 +/- 26.82 * 109/L vs. 101.96 +/-
      3.08 * 109/L, t=0.727, P=0.470). Sixty-four out of the 69 courses of DPMAS
      treatment were successfully completed, and 5 times were ended because of line
      coagulation. There was no uncomfortable symptom complained by 53 patients during
      the treatment. Hypotension occurred for 3 times, and discomfort and nausea during
      treatment were complained for 9 times. Low fever occurred 4 times after
      treatment. Those uncomfortable symptoms were relieved spontaneously or by
      symptomatic treatment. Psychological nursing care should be given to the patients
      before and after DPMAS to relieve anxiety. Circulating tubes should be well
      rinsed to prevent line coagulation. General condition of the patient should be
      closely monitored in order to adjust therapeutic measures. CONCLUSIONS: DPMAS
      could be effectively performed with a combination of two hemoperfusion machines
      without inadvertent side reactions, and it is safe in operation with smaller
      amount of plasma.

PMID- 24447356
TI  - [Aortic sinus aneurysm misdiagnosed as severe pneumonia, a case report].

PMID- 24447357
TI  - [The relationship between the levels and variability of blood glucose and the
      prognosis of massive cerebral infarction].
AB  - OBJECTIVE: To investigate the relationship between the levels and variability of
      blood glucose and the prognosis of massive cerebral infarction. METHODS: A
      retrospective study involving 72 massive cerebral infarction patients without
      diabetes mellitus admitted to Taizhou Enze Medical Centre Luqiao Hospital from
      January 2012 to June 2013 was conducted. The mean blood glucose level (GluAve),
      standard deviation of blood glucose level (GluSD), and coefficient of variation
      of blood glucose level (GluCV) during the first 72 hours were monitored.
      Complications such as cerebrocardiac syndrome, pulmonary infection, stress ulcer
      bleeding, urinary system infection, decubitus sore, electrolyte disturbances, and
      epileptic seizures were also recorded. According to the 28-day outcome after
      admission, patients were divided into survivor group (n=60) and non-survivor
      group (n=12). The values of GluAve, GluSD and GluCV were compared between the two
      groups. The patients were again divided into three groups based on the level of
      GluAve (<7.8, 7.8-11.1, >11.1 mmol/L). Finally, patients were divided into four
      groups based on the level of GluCV (<15%, 15%-30%, 30%-50%, >50%). Acute
      physiology and chronic health evaluation II (APACHEII) score, mortality, and
      complications were compared among groups. RESULTS: The levels of GluAve, GluSD
      and GluCV in non-survivor group were significantly higher than those in survivor
      group [GluAve: 17.91 +/- 5.33 mmol/L vs. 12.41 +/- 3.12 mmol/L, t=3.145, P=0.002;
      GluSD:2.87 +/- 1.96 mmol/L vs. 1.83 +/- 1.08 mmol/L, t=2.611, P=0.017; GluCV:
      (27.56 +/- 14.73)% vs. (20.12+/-10.97)%, t=2.020, P=0.043]. With the gradual
      increase of GluAve level, the mortality and total complication rate were elevated
      significantly [28-day mortality: 5.00% (1/20), 13.89% (5/36), 37.50% (6/16),
      chi2=7.16, P=0.028; total complication rate: 35.00% (7/20), 55.56% (20/36),
      93.75% (15/16), chi2=12.85, P=0.002]. But there was no significant difference in
      APACHEII score (9.80 +/- 4.17, 12.11 +/- 5.81, 13.69 +/- 6.57, F=2.241, P=0.114)
      and stress ulcer incidence rate [5.00% (1/20), 11.11% (4/36), 31.25% (5/16),
      chi2=5.59, P=0.061]. With the gradual increase of GluCV level, APACHEII score, 28
      day mortality, the incidence of various complications, and total complication
      rate were all raised significantly [APACHEII score: 7.00 +/- 1.56, 10.08 +/-
      1.88, 13.14 +/- 5.76, 16.76 +/- 7.17, F=12.486, P=0.000; mortality: 0 (0/15),
      8.70% (2/23), 23.81% (5/21), 38.46% (5/13), chi2=9.27, P=0.026; total
      complication rate: 40.00% (6/15), 47.83% (11/23), 57.14% (12/21), 100.00%
      (13/13), chi2=12.42, P=0.006]. CONCLUSIONS: Both the GluAve level and GluCV level
      are significantly correlated with the outcome of patients suffering from massive
      cerebral infarction. The change in GluCV level seems to be more sensitive in
      predicting the prognosis of massive cerebral infarction than GluAve.

PMID- 24447358
TI  - [A case of POEMS syndrome patient with main clinical manifestation of multiple
      acute cerebral infarction].

PMID- 24447359
TI  - [A study of visual expression on ulinastatin usage].
AB  - OBJECTIVE: To comprehensively understand the situation of research of the use of
      ulinastatin in clinical treatment, and to display the results with visual images.
      METHODS: The keywords of Bikunin, Ulinastatin, Urinastatin, urinary trypsin
      inhibitor in association with disease, treatment, therapy were searched with
      search engine from several academic websites with June 30th, 2012 (for English
      literature) or January 31st, 2013 (for Chinese literature) as the deadline.
      Bibexcel extracting keywords of diseases and that involving pathophysiology and
      biology accompanying the diseases and treatment mechanism of the diseases were
      used. Diseases were classified by ICD10, and the keywords of treatment mechanism
      were classified according to researchers' understanding and therapist suggestion.
      Word co-occurrence matrix of diseases and treatment mechanism words were
      constructed, and were expressed more accurately and intuitively by analyzing
      multidimensional scaling (MDS). Data were analyzed and charts were produced
      respectively using UCINET, SPSS 20.0 and Excel 2013 software. RESULTS: A total of
      3 660 articles were included for the analysis, including 1 428 in English and 2
      232 in Chinese. In English literature, 97 diseases with 796 times were analyzed
      and 17 disease categories distributed in ICD10. In Chinese literature, 220
      diseases with 2 153 times were analyzed and 14 disease categories distributed in
      ICD10. Seventy-four and 33 words involving treatment mechanism were respectively
      from English and Chinese literature, respectively, which could be roughly divided
      into three categories: immunity/inflammation, coagulation and genetic/metabolic.
      The word co-occurrence matrix analysis and MDS showed that the key word for
      mechanism of treatment appeared widely in different diseases, and a single
      disease might be expressed with different terms, while different diseases might
      have common foundation for ulinastatin treatment, though the foci of indication
      were also different. All data were found to be able to form visual images
      according to the aim of investigation. CONCLUSIONS: According to the data
      retrieved in this study, the field of ulinastatin treatment was quite widespread,
      involving hundreds of diseases, which were distributed in more than 10 categories
      of ICD10, and almost 100 keywords involving treatment mechanism were found.
      Although those diseases were varied, they have a common therapeutic foundation
      based on the word co-occurrence matrix analysis. All the present data were
      successfully transformed into visual image expression to achieve the goal of this
      study. On the other hand, the resolving methods and problems used in this study
      will be helpful for further similar studies.

PMID- 24447360
TI  - [Impact of time of initiation of renal replacement therapy for hypernatremia in
      patients with craniocerebral injury].

PMID- 24447361
TI  - [Treatment of sepsis and severe multiple organ dysfunction syndrome as a result
      of intestinal perforation subsequent to typhoid fever, a case report].

PMID- 24447362
TI  - [Research advance in CD147 and acute lung injury].

PMID- 24447363
TI  - Oleosins (24 and 18 kDa) are hydrolyzed not only in extracted soybean oil bodies
      but also in soybean germination.
AB  - After oil bodies (OBs) were extracted from ungerminated soybean by pH 6.8
      extraction, it was found that 24 and 18 kDa oleosins were hydrolyzed in the
      extracted OBs, which contained many OB extrinsic proteins (i.e., lipoxygenase,
      beta-conglycinin, gamma-conglycinin, beta-amylase, glycinin, Gly m Bd 30K (Bd
      30K), and P34 probable thiol protease (P34)) as well as OB intrinsic proteins. In
      this study, some properties (specificity, optimal pH and temperature) of the
      proteases of 24 and 18 kDa oleosins and the oleosin hydrolysis in soybean
      germination were examined, and the high relationship between Bd 30K/P34 and the
      proteases was also discussed. The results showed (1) the proteases were OB
      extrinsic proteins, which had high specificity to hydrolyze 24 and 18 kDa
      oleosins, and cleaved the specific peptide bonds to form limited hydrolyzed
      products; (2) 24 and 18 kDa oleosins were not hydrolyzed in the absence of Bd 30K
      and P34 (or some Tricine-SDS-PAGE undetectable proteins); (3) the protease of 24
      kDa oleosin had strong resistance to alkaline pH while that of 18 kDa oleosin had
      weak resistance to alkaline pH, and Bd 30K and P34, resolved into two spots on
      two-dimensional electrophoresis gel, also showed the same trend; (4) 16 kDa
      oleosin as well as 24 and 18 kDa oleosins were hydrolyzed in soybean germination,
      and Bd 30K and P34 were always contained in the extracted OBs from germinated
      soybean even when all oleosins were hydrolyzed; (5) the optimal temperature and
      pH of the proteases were respectively determined as in the ranges of 35-50 
      degrees C and pH 6.0-6.5, while 60  degrees C or pH 11.0 could denature them. 

PMID- 24447364
TI  - Mass spectrometric determination of prostanoids in rat hypothalamic
      paraventricular nucleus microdialysates.
AB  - The hypothalamic paraventricular nucleus (PVN) is one of the most important
      autonomic control centers in the brain. Several kinds of prostanoids, such as
      prostaglandin (PG) E2, are considered to act in the PVN as mediators of autonomic
      responses. In the present study, we used liquid chromatography ion trap tandem
      mass spectrometry (LC-ITMS(n)) to simultaneously quantify four prostanoids,
      thromboxane (Tx) B2, PGE2, PGD2 and 15-deoxy-?(12,14) (15d)-PGJ2 in PVN
      microdialysates from urethane-anesthetized rats. The quantification limits were
      estimated to be 0.05ng/mL for TxB2, 0.025ng/mL for PGE2, 0.1ng/mL for PGD2, and
      0.5ng/mL for 15d-PGJ2. The RSD% obtained from all prostanoids was <15%,
      indicating an acceptable level of reproducibility. LC-ITMS(n) analysis of rat PVN
      microdialysates revealed that TxA2 may play an important role in adrenomedullary
      outflow evoked by centrally administered N-methyl-d-aspartate, corticotrophin
      releasing factor and glucagon-like peptide-1. This is the first study to use LC
      ITMS(n) to analyze prostanoid levels in rat PVN microdialysates. This LC-ITMS(n)
      method will be useful for investigating the potential involvement of prostanoids
      in brain function. 

PMID- 24447365
TI  - Novel fragment-based QSAR modeling and combinatorial design of pyrazole-derived
      CRK3 inhibitors as potent antileishmanials.
AB  - The CRK3 cyclin-dependent kinase of Leishmania plays an important role in
      regulating the cell-cycle progression at the G2/M phase checkpoint transition,
      proliferation, and viability inside the host macrophage. In this study, a novel
      fragment-based QSAR model has been developed using 22 pyrazole-derived compounds
      exhibiting inhibitory activity against Leishmanial CRK3. Unlike other QSAR
      methods, this fragment-based method gives flexibility to study the relationship
      between molecular fragments of interest and their contribution for the variation
      in the biological response by evaluating cross-term fragment descriptors. Based
      on the fragment-based QSAR model, a combinatorial library was generated, and top
      two compounds were reported after predicting their activity. The QSAR model
      showed satisfactory statistical parameters for the data set (r(2) = 0.8752, q(2)
      = 0.6690, F-ratio = 30.37, and pred_r(2) = 0.8632) with four descriptors
      describing the nature of substituent groups and the environment of the
      substitution site. Evaluation of the model implied that electron-rich
      substitution at R1 position improves the inhibitory activity, while decline in
      inhibitory activity was observed in presence of nitrogen at R2 position. The
      analysis carried out in this study provides a substantial basis for consideration
      of the designed pyrazole-based leads as potent antileishmanial drugs.

PMID- 24447366
TI  - Identification of causal effects in the presence of nonignorable missing outcome
      values.
AB  - We consider a new approach to identify the causal effects of a binary treatment
      when the outcome is missing on a subset of units and dependence of nonresponse on
      the outcome cannot be ruled out even after conditioning on observed covariates.
      We provide sufficient conditions under which the availability of a binary
      instrument for nonresponse allows us to derive tighter identification intervals
      for causal effects in the whole population and to partially identify causal
      effects in some latent subgroups of units, named Principal Strata, defined by the
      nonresponse behavior in all possible combinations of treatment and instrument. A
      simulation study is used to assess the benefits of the presence versus the
      absence of an instrument for nonresponse. The simulation design is based on real
      health data, coming from a randomized trial on breast self-examination (BSE)
      affected by a large proportion of missing outcome data. An instrument for
      nonresponse is simulated considering alternative scenarios to discuss the key
      role of the instrument for nonresponse in identifying average causal effects in
      presence of nonignorable missing outcomes. We also investigate the potential
      inferential gains from using an instrument for nonresponse adopting a Bayesian
      approach for inference. In virtue of our theoretical and empirical results, we
      provide some recommendations on study designs for causal inference.

PMID- 24447367
TI  - Is thrombophilia associated with placenta-mediated pregnancy complications? A
      prospective cohort study.
AB  - BACKGROUND: Case control studies suggest that genetic thrombophilias increase the
      risk of placenta-mediated pregnancy complications (pregnancy loss, small for
      gestational age (SGA), preeclampsia and/or placental abruption). Cohort studies
      have not supported this association but were underpowered to detect small
      effects. OBJECTIVE: To determine if factor V Leiden (FVL) or the prothrombin gene
      mutation (PGM) were associated with placenta-mediated pregnancy complications.
      PATIENTS/METHODS: A prospective cohort of unselected, consenting pregnant women
      at three Canadian tertiary care hospitals had blood drawn in the early second
      trimester and were genotyped for FVL and PGM after delivery. The main outcome
      measure was a composite of pregnancy loss, SGA < 10th percentile, preeclampsia or
      placental abruption. RESULTS: Complete primary outcome and genetic data were
      available for 7343 women. Most were Caucasian (77.7%, n = 5707), mean age was
      30.4 (+/- 5.1) years, and half were nulliparous. There were 507 (6.9%) women with
      FVL and/or PGM; 11.64% had a placenta-mediated pregnancy complication. Of the
      remaining 6836 women, 11.23% experienced a complication. FVL and/or PGM was
      associated with a relative risk of 1.04 (95% CI, 0.81-1.33) for the composite
      outcome, with similar results after adjustment for important covariates.
      CONCLUSIONS: Carriers of FVL or PGM are not at significantly increased risk of
      these pregnancy complications.

PMID- 24447368
TI  - Distinct patterns of spread of prion infection in brains of mice expressing
      anchorless or anchored forms of prion protein.
AB  - BACKGROUND: In humans and animals, prion protein (PrP) is usually expressed as a
      glycophosphatidylinositol (GPI)-anchored membrane protein, but anchorless PrP may
      be pathogenic in humans with certain familial prion diseases. Anchored PrP
      expressed on neurons mediates spread of prions along axons in the peripheral and
      central nervous systems. However, the mechanism of prion spread in individuals
      expressing anchorless PrP is poorly understood. Here we studied prion spread
      within brain of mice expressing anchorless or anchored PrP. RESULTS: To create a
      localized initial point of infection, we microinjected scrapie in a 0.5
      microliter volume in the striatum. In this experiment, PrPres and gliosis were
      first detected in both types of mice at 40 days post-inoculation near the needle
      track. In mice with anchored PrP, PrPres appeared to spread via neurons to
      distant connected brain areas by the clinical endpoint at 150 days post
      inoculation. This PrPres was rarely associated with blood vessels. In contrast,
      in mice with anchorless PrP, PrPres spread did not follow neuronal circuitry, but
      instead followed a novel slower pattern utilizing the drainage system of the
      brain interstitial fluid (ISF) including perivascular areas adjacent to blood
      vessels, subependymal areas and spaces between axons in white matter tracts.
      CONCLUSIONS: In transgenic mice expressing anchorless PrP small amyloid-seeding
      PrPres aggregates appeared to be transported in the ISF, thus spreading
      development of cerebral amyloid angiopathy (CAA) throughout the brain. Spread of
      amyloid seeding by ISF may also occur in multiple human brain diseases involving
      CAA.

PMID- 24447369
TI  - Gene expression and nucleotide composition are associated with genic methylation
      level in Oryza sativa.
AB  - BACKGROUND: The methylation of cytosines at CpG dinucleotides, which plays an
      important role in gene expression regulation, is one of the most studied
      epigenetic modifications. Thus far, the detection of DNA methylation has been
      determined mostly by experimental methods, which are not only prone to bench
      effects and artifacts but are also time-consuming, expensive, and cannot be
      easily scaled up to many samples. It is therefore useful to develop computational
      prediction methods for DNA methylation. Our previous studies highlighted the
      existence of correlations between the GC content of the third codon position
      (GC3), methylation, and gene expression. We thus designed a model to predict
      methylation in Oryza sativa based on genomic sequence features and gene
      expression data. RESULTS: We first derive equations to describe the relationship
      between gene methylation levels, GC3, expression, length, and other gene
      compositional features. We next assess gene compositional features involving
      sixmers and their association with methylation levels and other gene level
      properties. By applying our sixmer-based approach on rice gene expression data we
      show that it can accurately predict methylation (Pearson's correlation
      coefficient r = 0.79) for the majority (79%) of the genes. Matlab code with our
      model is included. CONCLUSIONS: Gene expression variation can be used as
      predictors of gene methylation levels.

PMID- 24447370
TI  - The prevalence of osteoporosis in an older population with very high body mass
      index: evidence for an association.
AB  - BACKGROUND: Studies have demonstrated the beneficial effect of normal and high
      body mass index (BMI) upon risk of osteoporosis (OP). No study has investigated
      the prevalence of OP in an older population with a very high BMI (higher than 40
      kg/m(2) ). METHODS: Data of patients aged over 50 years that attended for a dual
      energy X-ray absorptiometry scan at a UK district general hospital were collated.
      The population was divided according to BMI increments of 5 kg/m(2) . The
      prevalence of OP for each BMI category was ascertained. Logistic regression
      analysis was used to investigate for significant associations between BMI and OP
      prevalence, adjusted for age, sex and number of OP risk factors. RESULTS: Data of
      10,796 study subjects were collated. Mean age was 67.34 years. Decreasing
      prevalence of OP was associated with increasing BMI up to 40 kg/m(2) , above
      which increasing BMI was associated with increasing prevalence of OP.
      CONCLUSIONS: The protective effect of increasing BMI exists up to 40 kg/m(2) . A
      BMI higher than 40 kg/m(2) is associated with increased prevalence of OP. This
      finding may be attributable to reduced level of bone weight bearing in
      individuals with a very high BMI.

PMID- 24447371
TI  - Social determinants of maternal self-rated health in South Western Sydney,
      Australia.
AB  - BACKGROUND: From 2000 a routine survey of mothers with newborn infants was
      commenced in South Western Sydney. The aim of this study is to examine the
      relationship of maternal self-rated health, as a measure of well-being, to
      various socio-demographic factors including measures of social capital, country
      of birth, financial status and employment. RESULTS: The sample consisted of
      23,534 mothers who delivered in South Western Sydney between 2004 and 2006. The
      data were collected as part of a routine post-partum assessment at 2-4 weeks
      postpartum. We examined the relationship of self-rated health with socio
      demographic variables using binary logistic regression. Worse self-rated health
      was reported in 4% of women. Variables which were found to be significantly
      associated with worse self-rated health were: poor financial situation, public
      housing accommodation, fathers employment, no car access, unplanned pregnancy,
      maternal smoking, poor emotional and social support, and motherhood being more
      difficult than expected. CONCLUSION: We confirmed the importance of social
      disadvantage and social isolation as independent risk factors for poor self
      reported health. The findings reported here provide further justification for
      public health interventions which increase support for socially excluded mothers
      and strengthen their connection to their community.

PMID- 24447372
TI  - Multiple mechanisms underlying acquired resistance to taxanes in selected
      docetaxel-resistant MCF-7 breast cancer cells.
AB  - BACKGROUND: Chemoresistance is a major factor involved in a poor response and
      reduced overall survival in patients with advanced breast cancer. Although
      extensive studies have been carried out to understand the mechanisms of
      chemoresistance, many questions remain unanswered. METHODS: In this research, we
      used two isogenic MCF-7 breast cancer cell lines selected for resistance to
      doxorubicin (MCF-7DOX) or docetaxel (MCF-7TXT) and the wild type parental cell
      line (MCF-7CC) to study mechanisms underlying acquired resistance to taxanes in
      MCF-7TXT cells. Cytotoxicity assay, immunoblotting, indirect immunofluorescence
      and live imaging were used to study the drug resistance, the expression levels of
      drug transporters and various tubulin isoforms, apoptosis, microtubule formation,
      and microtubule dynamics. RESULTS: MCF-7TXT cells were cross resistant to
      paclitaxel, but not to doxorubicin. MCF-7DOX cells were not cross-resistant to
      taxanes. We also showed that multiple mechanisms are involved in the resistance
      to taxanes in MCF-7TXT cells. Firstly, MCF-7TXT cells express higher level of
      ABCB1. Secondly, the microtubule dynamics of MCF-7TXT cells are weak and
      insensitive to the docetaxel treatment, which may partially explain why docetaxel
      is less effective in inducing M-phase arrest and apoptosis in MCF-7TXT cells in
      comparison with MCF-7CC cells. Moreover, MCF-7TXT cells express relatively higher
      levels of beta2- and beta4-tubulin and relatively lower levels of beta3-tubulin
      than both MCF-7CC and MCF-7DOX cells. The subcellular localization of various
      beta-tubulin isoforms in MCF-7TXT cells is also different from that in MCF-7CC
      and MCF-7DOX cells. CONCLUSION: Multiple mechanisms are involved in the
      resistance to taxanes in MCF-7TXT cells. The high expression level of ABCB1, the
      specific composition and localization of beta-tubulin isoforms, the weak
      microtubule dynamics and its insensitivity to docetaxel may all contribute to the
      acquired resistance of MCF-7TXT cells to taxanes.

PMID- 24447373
TI  - Retrospective analysis of the outcome of patients with idiopathic inflammatory
      myopathy: a long-term follow-up study.
AB  - OBJECTIVES: Several factors have been implicated in the prognosis of idiopathic
      inflammatory myopathies, including age, gender, delay in diagnosis, neoplasia,
      creatine kinase levels and some autoantibodies. We have reviewed the main factors
      contributing to mortality in patients with idiopathic inflammatory myopathy (IIM)
      diagnosed between 1976 and 2007 who were followed for at least 5 years in the
      Rheumatology Unit at University College Hospital in London. METHODS: An
      observational retrospective study was carried out on patients with IIM diagnosed
      between 1976 and 2007. All the patients fullfilled at least three out of four of
      the Bohan and Peter criteria. The subjects were divided into the following
      groups: adult-onset polymyositis (APM); adult-onset dermatomyositis (ADM);
      juvenile dermatomyositis (JDM); Overlap syndromes with another autoimmune
      rheumatic disease. RESULTS: 90 patients were identified. The female to male ratio
      was 2.5:1 and the mean age at diagnosis was 38.5 years (SD 15.03). 47.8% of the
      patients had APM, 30% adult-onset ADM, 15.6% Overlap and 6.7% JDM. Among the
      extramuscular features, 18.9% had pulmonary involvement. In 70% the highest CK
      was >5 times the upper normal. Prednisolone was prescribed in 98.9%. 11.1%
      received rituximab. 34.4% had monophasic, 31.1% relapsing and remitting and 34.4%
      continuous progressive course of the disease. The median follow-up was 11.5 years
      (IQR 12.00). 14.4% of the patients died, 30.8% due to infection, 30.8% from a
      cardiovascular event and 23.1% due to neoplasia. The 1, 5 and 10-year survival
      was 100%, 97.8% and 91%, respectively. Male gender (Hazards Ratio (HR) 3.222;
      p=0.037), pulmonary involvement (HR 5.247; p=0.009), chronic progressive course
      (HR 3.711; p=0.030) and use of rituximab (HR 3.562; p=0.036) were the only risk
      factors to be statistically significantly associated (p<0.05) with death.
      CONCLUSIONS: We conclude that long-term survival in these patients is generally
      quite good with an estimated 10-year survival >90% in our cohort, which is even
      higher than previously reported.

PMID- 24447374
TI  - Turkish health system reform from the people's perspective: a cross sectional
      study.
AB  - BACKGROUND: Since 2003, Turkey has implemented major health care reforms to
      develop easily accessible, high-quality, efficient, and effective healthcare
      services for the population. The purpose of this study was to bring out opinions
      of the Turkish people on health system reform process, focusing on several
      aspects of health system and assessing whether the public prefer the current
      health system or that provided a decade ago. METHODS: A cross sectional survey
      study was carried out in Turkey to collect data on people's opinions on the
      healthcare reforms. Data was collected via self administered household's
      structured questionnaire. A five-point Likert-type scale was used to score the
      closed comparative statements. Each statement had response categories ranging
      from (1) "strongly agree" to (5) "strongly disagree." A total of 482 heads of
      households (response rate: 71.7%) with the mean age of (46.60 years) were
      selected using a multi stage sampling technique from seven geographical regions
      in Turkey from October 2011 to January 2012. Multiple logistic regressions were
      performed to identify significant contributing factors in this study. RESULTS:
      Employing descriptive statistics it is observed that among the respondents, more
      than two third of the population believes that the changes have had positive
      effects on the health system. A vast majority of respondents (82.0%) believed
      that there was an increase in accessibility, 73.7% thought more availability of
      health resources, 72.6% alleged improved quality of care, and 72.6% believed
      better attitude of politician/mass media due to the changes in the last 10 years.
      Indeed, the majority of respondents (77.6%) prefer the current health care system
      than the past. In multivariate analysis, there was a statistically significant
      relationship between characteristics and opinions of the respondents. The
      elderly, married females, perceived themselves healthy and those who believe that
      people are happier now than 10 years ago have a more positive opinion of the
      changes. While, the single unemployed from rural region who perceived themselves
      as unhealthy and believe that people are unhappy now compare to ten years ago
      showed less positive opinions. CONCLUSIONS: Hence, we conclude that from the
      people's perspective overall the health system reforms were most likely
      successful.

PMID- 24447375
TI  - Brain biopsy in AIDS patients: diagnostic yield and treatment applications.
AB  - OBJECTIVE: Central nervous system involvement in AIDS patients can present at any
      stage of the disease. Brain lesions detected in imaging studies are usually
      treated empirically. A brain biopsy is indicated in the absence of clinical and
      radiologic improvement. In the present study, 16 AIDS patients underwent brain
      biopsy. We evaluated the diagnostic yield of the brain biopsy and the changes in
      the disease course. MATERIALS AND METHODS: Sixteen consecutive AIDS patients (12
      men, 4 women; mean age 40.8 years) underwent a brain biopsy at Sheba Medical
      Center between 1997 and 2009. A retrospective analysis was performed and the
      clinical outcome was recorded. RESULTS: Median CD4 count before biopsy was 62.6.
      Magnetic resonance images revealed multiple lesions in 12 patients and enhancing
      lesions in 12 patients. A total of 19 biopsies were performed in 16 patients. In
      the present series, the initial procedures provided a diagnostic yield of 81.25%
      (13 diagnostic cases from 16 procedures in 16 patients). Two of these patients
      underwent repeated biopsies that were eventually diagnostic . If repeated
      biopsies were taken into consideration, the diagnostic yield was 93.75% (15
      diagnostic cases in 16 patients). The rate of hemorrhagic complications was 10.5%
      (2 hemorrhages in 19 procedures).Pathologic examination revealed parasitic and
      fungal infections in 6 patients (6/16; 38%), progressive multifocal
      leukoencephalopathy in 4 patients (4/16; 25%), AIDS encephalopathy in 4 patients
      (4/16; 25%), and lymphoma in 1 patient (1/16; 6%). One patient had a nonspecific
      inflammatory process (6%). The treatment modality was modified in 12 patients and
      led to clinical and radiologic improvement in 8 patients. CONCLUSIONS: Brain
      biopsy should be considered when empiric treatment of central nervous system
      lesions in AIDS patients fails. Biopsy is diagnostic in the majority of patients.
      The diagnosis allows for treatment modifications, which lead to clinical and
      radiologic improvement in some patients.

PMID- 24447376
TI  - Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients
      with schizophrenia.
AB  - AIM: Patients with schizophrenia have been reported to perform worse than non
      schizophrenic populations on neuropsychological tests, which may be affected by
      cultural factors. The aim of this study was to examine the performance of a
      sizable number of patients with schizophrenia on the Japanese version of the
      Wechsler Adult Intelligence Scale-III (WAIS-III) compared with healthy controls.
      METHODS: Performance on the WAIS-III was evaluated in 157 Japanese patients with
      schizophrenia and in 264 healthy control subjects. RESULTS: All IQ scores and
      four indices from the WAIS-III were impaired for patients with schizophrenia
      compared with healthy controls. Processing Speed was markedly disturbed,
      approximately 2 SD below that of the healthy control group. Among the 13
      subtests, Comprehension (z = -1.70, d = 1.55), Digit Symbol Coding (z = -1.84, d
      = 1.88), and Symbol Search (z = -1.85, d = 1.77) were profoundly impaired
      relative to the healthy controls. CONCLUSION: These results indicate that the
      pattern and degree of impairment, as evaluated by the WAIS-III, in Japanese
      patients are similar to those previously reported in English-speaking patients
      and that the deficits of some neuropsychological domains relevant to functional
      outcomes are universally characteristic of schizophrenia.

PMID- 24447377
TI  - Evaluation of the reproductive and developmental toxicity of 6:2 fluorotelomer
      alcohol in rats.
AB  - 6:2 Fluorotelomer alcohol (6:2 FTOH) was evaluated for potential developmental
      and reproductive toxicity. 6:2 FTOH was administered by oral gavage to Sprague
      Dawley rats as a suspension in 0.5% aqueous methylcellulose at dosages of 5, 25,
      125, or 250 mg/kg/day. The developmental toxicity study was performed in
      accordance with the Organization for Economic Development (OECD) Test Guideline
      414, and the one-generation reproductive toxicity study was performed in
      accordance with the OECD Test Guideline 415. For the developmental toxicity
      study, adverse maternal toxicity observed at 250 mg/kg/day included reductions in
      body weight parameters and food consumption. Evidence of developmental toxicity
      was limited to increases in skeletal variations (ossification delays in the skull
      and rib alterations) at 250 mg/kg/day. There were no adverse maternal or
      developmental effects observed at 5, 25, or 125 mg/kg/day and there were no
      effects on reproductive outcome or quantitative litter data at any dose level.
      For the one-generation reproduction toxicity study, systemic parental and
      developmental toxicity were observed at 125 and 250 mg/kg/day. At 250 mg/kg/day,
      there was increased mortality among male and female parental rats, effects on
      body weight parameters, food consumption, and clinical signs, and there were
      effects on offspring survival indices and body weights. At 125 mg/kg/day, there
      was an increase in mortality in parental males only, and parental toxicity was
      limited to effects on body weight gain, food consumption (lactation), and
      clinical signs. Uterine weights were decreased at 125 and 250 mg/kg/day, although
      there were no corroborative histopathological changes. At 125 mg/kg/day, pup
      mortality was increased on lactation day 1, and body weights of the offspring
      were decreased during the second half of lactation. There was no evidence of
      either parental or developmental toxicity at 5 or 25mg/kg/day, and there were no
      effects on reproductive outcome at any dose level. Based on these data, 6:2 FTOH
      is not a selective reproductive or developmental toxicant at dosages that induce
      clear maternal/parental toxicity. Therefore, 6:2 FTOH would not be classified for
      reproductive/developmental toxicity under the United Nations' Globally Harmonized
      System of Classification and Labeling of Chemicals.

PMID- 24447379
TI  - A sit-down with Dr. Denton Cooley.

PMID- 24447380
TI  - A sit-down with Dr. Denton Cooley. Interview by Douglas S. Moodie and Ericka S.
      McLaughlin.

PMID- 24447378
TI  - Use of OpdA, an organophosphorus (OP) hydrolase, prevents lethality in an African
      green monkey model of acute OP poisoning.
AB  - Organophosphorus (OP) pesticides are a diverse class of acetylcholinesterase
      (AChE) inhibitors that are responsible for tremendous morbidity and mortality
      worldwide, killing approximately 300,000 people annually. Enzymatic hydrolysis of
      OPs is a potential therapy for acute poisoning. OpdA, an OP hydrolase isolated
      from Agrobacterium radiobacter, has been shown to decrease lethality in rodent
      models of OP poisoning. This study investigated the effects of OpdA on AChE
      activity, plasma concentrations of OP, and signs of toxicity after administration
      of dichlorvos to nonhuman primates. A dose of 75 mg/kg dichlorvos given orally
      caused apnea within 10 min with a progressive decrease in heart rate. Blood AChE
      activity decreased to zero within 10 min. Respirations and AChE activity did not
      recover. The mean dichlorvos concentration rose to a peak of 0.66 MUg/ml. Treated
      monkeys received 1.2mg/kg OpdA iv immediately after poisoning with dichlorvos. In
      Opda-treated animals, heart and respiratory rates were unchanged from baseline
      over a 240-minute observation period. AChE activity slowly declined, but remained
      above 25% of baseline for the entire duration. Dichlorvos concentrations reached
      a mean peak of 0.19 MUg/ml at 40 min after poisoning and decreased to a mean of
      0.05 MUg/ml at 240 min. These results show that OpdA hydrolyzes dichlorvos in an
      African green monkey model of lethal poisoning, delays AChE inhibition, and
      prevents lethality.

PMID- 24447381
TI  - Reemergence of Rift Valley fever, Mauritania, 2010.
AB  - A Rift Valley fever (RVF) outbreak in humans and animals occurred in Mauritania
      in 2010. Thirty cases of RVF in humans and 3 deaths were identified. RVFV
      isolates were recovered from humans, camels, sheep, goats, and Culex antennatus
      mosquitoes. Phylogenetic analysis of isolates indicated a virus origin from
      western Africa. 

PMID- 24447382
TI  - Poxvirus viability and signatures in historical relics.
AB  - Although it has been >30 years since the eradication of smallpox, the unearthing
      of well-preserved tissue material in which the virus may reside has called into
      question the viability of variola virus decades or centuries after its original
      occurrence. Experimental data to address the long-term stability and viability of
      the virus are limited. There are several instances of well-preserved corpses and
      tissues that have been examined for poxvirus viability and viral DNA. These
      historical specimens cause concern for potential exposures, and each situation
      should be approached cautiously and independently with the available information.
      Nevertheless, these specimens provide information on the history of a major
      disease and vaccination against it. 

PMID- 24447383
TI  - The reach, transferability, and impact of the Evidence-Based Practice
      Questionnaire: a methodological and narrative literature review.
AB  - BACKGROUND: Since the 1990s, evidence-based practice (EBP) has been increasingly
      emphasized in nursing, but its implementation is still sometimes met with
      confusion and resistance. Therefore, identifying factors affecting its
      implementation is crucial. The Evidence-Based Practice Questionnaire (EBPQ) was
      published in 2006, addressing a need for a robust measure of nurses' practice of,
      attitudes toward, and knowledge of EBP. The growing body of professionals using
      the questionnaire means that a review of its reach, transferability, and impact
      is timely. AIMS: The aims of this review were threefold: (a) identify the
      situations in which the EBPQ has been used in both published and unpublished
      research internationally (Reach); (b) collate the psychometric properties of the
      EBPQ from the research reviewed (Transferability); and (c) discuss the study's
      findings to shed new light on issues facing professionals in implementing EBP,
      and possible future directions for research (Impact). METHODS: Literature
      searches on studies reported between 2006 and July 2012 inclusive were conducted
      using the terms "Evidence-Based Practice Questionnaire" and "EBPQ." Green,
      Johnson and Adams's guidelines for completing narrative literature reviews and
      Terwee et al.'s framework for reporting questionnaires' psychometric properties
      were adopted to ensure rigor. FINDINGS: Twenty-seven studies were reviewed in
      which the EBPQ had been translated into five different languages and used with a
      variety of professional groups. The questionnaire demonstrated convergent and
      discriminant validity and good internal reliability. Research adopting the
      questionnaire identified a range of variables related to EBP implementation,
      including qualification route and job role. LINKING EVIDENCE TO ACTION:
      Assessment of organizational culture and workforce training needs prior to
      developing educational interventions is crucial. The EBPQ has the potential to
      provide further understanding of these and other issues faced by professionals
      when implementing EBP.

PMID- 24447385
TI  - Phytoremediation of cyanophos insecticide by Plantago major L. in water.
AB  - Cyanophos is commonly used in Egypt to control various agricultural and
      horticultural pests. It is not easily hydrolyzed and thus they are highly
      persistent and accumulate in various aquatic compartments such as rivers and
      lakes. Such issues may be solved by phytoremediation, which is the use of plants
      for the cleanup of pollutants. Here, we tested Plantago major L. to clean water
      polluted with cyanophos insecticide under laboratory conditions.The biosorption
      capacity (KF) of cyanophos were 76.91, 26.18 and 21.09 MUg/g for dry roots, fruit
      (seeds with shells) and leaves of the Plantago major L., respectively. Viable
      Plantago major L. in water significantly reduced cyanophos by 11.0% & 94.7%
      during 2 hours & 9 days of exposure as compared with 0.8% & 36.9% in water
      without the plantain. In water with plantain, cyanophos significantly accumulated
      in plantain roots and leaves to reach maximum levels after two and four hours of
      treatment, respectively. After 1 day, the concentration of cyanophos decreased in
      roots and shoots until the end of testing. Three major degradation products were
      detected at roots and leaf samples. Here we demonstrate that plantago major L.
      removes efficiently cyanophos residue in water and has a potential activity for
      pesticide phytoremediation. 

PMID- 24447384
TI  - Hydroxyapatite and calcified elastin induce osteoblast-like differentiation in
      rat aortic smooth muscle cells.
AB  - Vascular calcification can be categorized into two different types. Intimal
      calcification related to atherosclerosis and elastin-specific medial arterial
      calcification (MAC). Osteoblast-like differentiation of vascular smooth muscle
      cells (VSMCs) has been shown in both types; however, how this relates to
      initiation of vascular calcification is unclear. We hypothesize that the initial
      deposition of hydroxyapatite-like mineral in MAC occurs on degraded elastin first
      and that causes osteogenic transformation of VSMCs. To test this, rat aortic
      smooth muscle cells (RASMCs) were cultured on hydroxyapatite crystals and
      calcified aortic elastin. Using RT-PCR and specific protein assays, we
      demonstrate that RASMCs lose their smooth muscle lineage markers like alpha
      smooth muscle actin (SMA) and myosin heavy chain (MHC) and undergo
      chondrogenic/osteogenic transformation. This is indicated by an increase in the
      expression of typical chondrogenic proteins such as aggrecan, collagen type II
      alpha 1(Col2a1) and bone proteins such as runt-related transcription factor 2
      (RUNX2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, when
      calcified conditions are removed, cells return to their original phenotype. Our
      data supports the hypothesis that elastin degradation and calcification precedes
      VSMCs' osteoblast-like differentiation. 

PMID- 24447386
TI  - Temporal genetic structure in a poecilogonous polychaete: the interplay of
      developmental mode and environmental stochasticity.
AB  - BACKGROUND: Temporal variation in the genetic structure of populations can be
      caused by multiple factors, including natural selection, stochastic environmental
      variation, migration, or genetic drift. In benthic marine species, the
      developmental mode of larvae may indicate a possibility for temporal genetic
      variation: species with dispersive planktonic larvae are expected to be more
      likely to show temporal genetic variation than species with benthic or brooded
      non-dispersive larvae, due to differences in larval mortality and dispersal
      ability. We examined temporal genetic structure in populations of Pygospio
      elegans, a poecilogonous polychaete with within-species variation in
      developmental mode. P. elegans produces either planktonic, benthic, or
      intermediate larvae, varying both among and within populations, providing a
      within-species test of the generality of a relationship between temporal genetic
      variation and larval developmental mode. RESULTS: In contrast to our
      expectations, our microsatellite analyses of P. elegans revealed temporal genetic
      stability in the UK population with planktonic larvae, whereas there was
      variation indicative of drift in temporal samples of the populations from the
      Baltic Sea, which have predominantly benthic and intermediate larvae. We also
      detected temporal variation in relatedness within these populations. A large
      temporal shift in genetic structure was detected in a population from the
      Netherlands, having multiple developmental modes. This shift could have been
      caused by local extiction due to extreme environmental conditions and
      (re)colonization by planktonic larvae from neighboring populations. CONCLUSIONS:
      In our study of P. elegans, temporal genetic variation appears to be due to not
      only larval developmental mode, but also the stochastic environment of adults.
      Large temporal genetic shifts may be more likely in marine intertidal habitats
      (e.g. North Sea and Wadden Sea) which are more prone to environmental
      stochasticity than the sub-tidal Baltic habitats. Sub-tidal and/or brackish (less
      saline) habitats may support smaller P. elegans populations and these may be more
      susceptible to the effects of random genetic drift. Moreover, higher frequencies
      of asexual reproduction and the benthic larval developmental mode in these
      populations leads to higher relatedness and contributes to drift. Our results
      indicate that a general relationship between larval developmental mode and
      temporal genetic variation may not exist.

PMID- 24447388
TI  - Acupuncture for surgical conditions: an overview of systematic reviews.
AB  - AIM: Several systematic reviews (SRs) of acupuncture for surgical conditions have
      recently been published with sometimes contradicting results. The aim of this
      overview was to summarise recent SRs of acupuncture for surgical conditions.
      METHOD: Thirteen electronic databases were searched for relevant reviews
      published since 2000. Data were extracted by two independent reviewers according
      to predefined criteria. RESULTS: Twelve SRs met our inclusion criteria. They
      related to the prevention or treatment of postoperative nausea and vomiting as
      well as to surgical or postoperative pain. Their results were far from uniform,
      and several caveats need to be considered. CONCLUSION: The evidence is
      insufficient to suggest that acupuncture is an effective intervention in surgical
      settings. More rigorous research seems warranted. This protocol was registered
      with PROSPERO database (registration number: CRD42013004817).

PMID- 24447387
TI  - Effectiveness of option B highly active antiretroviral therapy (HAART) prevention
      of mother-to-child transmission (PMTCT) in pregnant HIV women.
AB  - BACKGROUND: Ensuring that no baby is born with HIV is an essential step towards
      achieving an AIDS-free generation. To achieve this, strategies that decouple
      links between childbirth and HIV transmission are necessary. Traditional forms of
      prevention of mother-to-child transmission of HIV (PMTCT), has been recommended.
      Recognizing the importance and challenges of combination of methods to achieve
      rapid PMTCT, the World Health Organization (WHO) recommended option B Highly
      Active Antiretroviral Therapy (HAART) for all HIV-positive pregnant women. This
      study aimed to evaluate the effectiveness of the HAART in PMTCT. A cohort of HIV
      infected pregnant women in Kenya were obtained from the DREAM Center, Nairobi.
      The study participants underwent adherence counselling and Option B of HAART
      [Nevirapine(NVP) + Lamivudine + Zidovudine] at the fourth week of gestation
      followed by an intravenous NVP administration intrapartum and postpartum NVP
      syrup to the respective infants for six weeks. Absolute pre-HAART and post-HAART
      CD4 counts and viral loads counts were determined. Comparison of the CD4 counts
      and viral loads before and after administration of HAART were done using
      Wilcoxon's Matched Pairs Signed-Ranks Test. FINDINGS: The mean absolute CD4 cell
      counts in mothers after administration of HAART was significantly higher (Z =
      15.664, p < 0.001) than before the administration of HAART). Also the viral load
      of the mothers significantly (Z = 11.324, p < 0.001) reduced following HAART
      treatment. Following the HAART administration in mothers, up to 90% of children
      were confirmed to be HIV negative. CONCLUSION: Administration of HAART to mothers
      and children demonstrated an effective mechanism of PMTCT. However, other aspects
      of HAART such as adherence, costs, mothers behaviour during HAART, and the child
      feeding programme during the therapy should further be evaluated and ascertained
      how they can affect the overall efficacy of option B HAART in PMTCT.

PMID- 24447390
TI  - The origin of Behcet's disease geoepidemiology: possible role of a dual microbial
      driven genetic selection.
AB  - It is recognised that the genetic profiles that give rise to chronic inflammatory
      diseases, under the influence of environmental agents, might have been implicated
      in the host defence mechanism against lethal infections in the past. Behcet's
      disease (BD) is an immune-mediated inflammatory disease, expressed as vasculitis,
      triggered by environmental factors in genetically susceptible individuals. We
      carried out a review of published data to draw up an evolutionary adaptation
      model, as Author's perspective, for genetic susceptibility factors and
      inflammatory immune response involved in BD pathogenesis. Two lethal infectious
      agents, Plasmodium Falciparum and Yersinia Pestis, are proposed as the putative
      driving forces that favoured the fixing of the major genetic susceptibility
      factors to BD, thus determining its geoepidemiology. Further studies are needed
      to confirm the validity of this evolutionary model which includes and integrates
      the key insights of previous hypotheses. 

PMID- 24447389
TI  - Efficacy and safety of widely used treatments for macular oedema secondary to
      retinal vein occlusion: a systematic review.
AB  - BACKGROUND: Macular oedema secondary to retinal vein occlusion (RVO) can cause
      vision loss due to blockage of the central retinal vein (CRVO) or a branch
      retinal vein (BRVO). This systematic review assessed the efficacies of widely
      used treatments for macular oedema secondary to RVO and the feasibility of
      conducting indirect comparisons between these therapies. METHODS: A systematic
      review was undertaken in November 2010, including a literature search for trials
      in medical databases and relevant websites. Abstracts, conference presentations
      and unpublished studies were considered. Studies were data-extracted and quality
      assessed by two independent researchers. Outcome measures included the mean
      change in best corrected visual acuity (BCVA) from baseline in the study eye
      and/or number of patients gaining at least 10 letters from baseline to 6 months
      or the nearest equivalent time point. RESULTS: Fourteen unique randomized
      controlled trials (RCTs) were identified. Ranibizumab 0.5 mg produced greater
      improvements in BCVA at 6 months than sham in BRVO (mean difference 11.0 letters,
      95% confidence interval [CI] 7.83, 14.17) and CRVO (mean difference 14.10
      letters, 95% CI 10.51, 17.69) in two double-blind sham-controlled RCTs. Pooled
      data from two double-blind, sham-controlled RCTs showed that improvements in BCVA
      were also significantly better for dexamethasone intravitreal (IVT) implant 0.7
      mg compared with sham in patients with BRVO or CRVO (mean difference 2.5 letters,
      95% CI 0.7, 4.3); the difference was significant for BRVO alone, but not CRVO
      alone. A significantly greater proportion of patients with BRVO gained >=15
      letters with laser therapy vs. no treatment at 36 months in a large prospective
      RCT (odds ratio 3.16, 95% CI 1.25, 8.00), whereas no difference was observed at 9
      months in a smaller study. Three studies reported no benefit for laser therapy in
      CRVO. No indirect comparisons with ranibizumab were feasible due to differences
      in study design and baseline characteristics. CONCLUSIONS: Data from RCTs for
      ranibizumab and dexamethasone IVT demonstrate that both new agents constitute
      significant improvements over the previously widely accepted standard of care
      (laser therapy) for the treatment of BRVO and CRVO. However, head-to-head studies
      are needed to assess the relative efficacies of licensed therapies for RVO.

PMID- 24447391
TI  - Introduction to causal diagrams for confounder selection.
AB  - In respiratory health research, interest often lies in estimating the effect of
      an exposure on a health outcome. If randomization of the exposure of interest is
      not possible, estimating its effect is typically complicated by confounding bias.
      This can often be dealt with by controlling for the variables causing the
      confounding, if measured, in the statistical analysis. Common statistical methods
      used to achieve this include multivariable regression models adjusting for
      selected confounding variables or stratification on those variables. Therefore, a
      key question is which measured variables need to be controlled for in order to
      remove confounding. An approach to confounder-selection based on the use of
      causal diagrams (often called directed acyclic graphs) is discussed. A causal
      diagram is a visual representation of the causal relationships believed to exist
      between the variables of interest, including the exposure, outcome and potential
      confounding variables. After creating a causal diagram for the research question,
      an intuitive and easy-to-use set of rules can be applied, based on a foundation
      of rigorous mathematics, to decide which measured variables must be controlled
      for in the statistical analysis in order to remove confounding, to the extent
      that is possible using the available data. This approach is illustrated by
      constructing a causal diagram for the research question: 'Does personal smoking
      affect the risk of subsequent asthma?'. Using data taken from the Tasmanian
      Longitudinal Health Study, the statistical analysis suggested by the causal
      diagram approach was performed. 

PMID- 24447393
TI  - A new sensory organ in "primitive" molluscs (Polyplacophora: Lepidopleurida), and
      its context in the nervous system of chitons.
AB  - INTRODUCTION: Chitons (Polyplacophora) are molluscs considered to have a simple
      nervous system without cephalisation. The position of the class within Mollusca
      is the topic of extensive debate and neuroanatomical characters can provide new
      sources of phylogenetic data as well as insights into the fundamental biology of
      the organisms. We report a new discrete anterior sensory structure in chitons,
      occurring throughout Lepidopleurida, the order of living chitons that retains
      plesiomorphic characteristics. RESULTS: The novel "Schwabe organ" is clearly
      visible on living animals as a pair of streaks of brown or purplish pigment on
      the roof of the pallial cavity, lateral to or partly covered by the mouth
      lappets. We describe the histology and ultrastructure of the anterior nervous
      system, including the Schwabe organ, in two lepidopleuran chitons using light and
      electron microscopy. The oesophageal nerve ring is greatly enlarged and displays
      ganglionic structure, with the neuropil surrounded by neural somata. The Schwabe
      organ is innervated by the lateral nerve cord, and dense bundles of nerve fibres
      running through the Schwabe organ epithelium are frequently surrounded by the
      pigment granules which characterise the organ. Basal cells projecting to the
      epithelial surface and cells bearing a large number of ciliary structures may be
      indicative of sensory function. The Schwabe organ is present in all genera within
      Lepidopleurida (and absent throughout Chitonida) and represents a novel
      anatomical synapomorphy of the clade. CONCLUSIONS: The Schwabe organ is a
      pigmented sensory organ, found on the ventral surface of deep-sea and shallow
      water chitons; although its anatomy is well understood, its function remains
      unknown. The anterior commissure of the chiton oesophagial nerve ring can be
      considered a brain. Our thorough review of the chiton central nervous system, and
      particularly the sensory organs of the pallial cavity, provides a context to
      interpret neuroanatomical homology and assess this new sense organ.

PMID- 24447392
TI  - Long term liver specific glucokinase gene defect induced diabetic cardiomyopathy
      by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK.
AB  - BACKGROUND: The liver-specific glucokinase knockout (gckw/-) mouse experiences
      long-term hyperglycemia and insulin resistance. This study was designed to
      evaluate the functional and structural changes in the myocardium of 60 week-old
      gckw/- mice, and to investigate the effect of rosiglitazone on the myocardium in
      this model. METHODS: 60 week-old gckw/- mice were randomly divided into 3 groups:
      gckw/-, gckw/- mice treated with insulin (1 U/kg) and gckw/- mice treated with
      rosiglitazone (18 mg/kg). Insulin or rosiglitazone treatment was for 4 weeks.
      Gckw/w litermates were used as controls. Echocardiography, electrocardiogram,
      biochemical, histopathological, ultrastructural, real time PCR and Western blot
      studies were performed to examine for structural and functional changes. RESULTS:
      Long-term liver-specific gck knockout in mice elicits hyperglycaemia and insulin
      resistance. Compared to age matched gckw/w mice, 60 week-old gckw/- mice showed
      decreased LV internal dimension, increased posterior wall thickness, lengthened
      PR and QRS intervals, up-regulated MLC2 protein expression, decreased SOD
      activity, increased MDA levels and up-regulated Cyba mRNA. Morphological studies
      revealed that there was an increase in the amount of PAS and Masson positively
      stained material, as did the number and proportion of the cell occupied by
      mitochondria in the gckw/- mice. Western blot analysis revealed that the levels
      of the insulin receptor, Akt, phosphorylated AMPK beta and phosphorylated ACC
      were reduced in gckw/- mice. These effects were partly attenuated or ablated by
      treatment with rosiglitazone. CONCLUSIONS: Our results indicate that changes in
      the myocardium occur in the liver-specific glucokinase knockout mouse and suggest
      that reduced glucokinase expression in the liver may induce diabetic
      cardiomyopathy by up regulating NADPH oxidase and down regulating insulin
      receptor and p-AMPK protein levels. Rosiglitazone treatment may protect against
      diabetic cardiomyopathy by altering the levels of a set of proteins involved in
      cardiac damage.

PMID- 24447394
TI  - Burkholderia pseudomallei isolates in 2 pet iguanas, California, USA.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, was isolated from
      abscesses of 2 pet green iguanas in California, USA. The international trade in
      iguanas may contribute to importation of this pathogen into countries where it is
      not endemic and put persons exposed to these animals at risk for infection. 

PMID- 24447395
TI  - Adiposity and hand osteoarthritis: the Netherlands Epidemiology of Obesity study.
AB  - INTRODUCTION: Obesity, usually characterized by the body mass index (BMI), is a
      risk factor for hand osteoarthritis (OA). We investigated whether adipose tissue
      and abdominal fat distribution are associated with hand OA. METHODS: The
      Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged
      45 to 65 years, including 5315 participants (53% women, median BMI 29.9 kg/m2).
      Fat percentage and fat mass (FM) (kg) were estimated using bioelectrical
      impedance analysis. The waist-to-hip ratio (WHR) was calculated. In 1721
      participants, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)
      (cm2) were assessed using abdominal MR imaging. Hand OA was defined according to
      the ACR criteria. RESULTS: Hand OA was present in 8% of men and 20% of women. Fat
      percentage was associated with hand OA in men (OR 1.34 (95% CI 1.11 to 1.61)) and
      women (OR 1.26 (1.05 to 1.51)), as was FM. WHR was associated with hand OA in men
      (OR 1.45 (1.13 to 1.85)), and to a lesser extent in women (OR 1.17 (1.00 to
      1.36)). Subgroup analysis revealed that VAT was associated with hand OA in men
      (OR1.33 (1.01 to 1.75)). This association increased after additional adjustment
      for FM (OR 1.51 (1.13 to 2.03)). CONCLUSIONS: Fat percentage, FM and WHR were
      associated with hand OA. VAT was associated with hand OA in men, suggesting
      involvement of visceral fat in hand OA.

PMID- 24447396
TI  - Proliferator-activated receptor gamma Pro12Ala interacts with the insulin
      receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and
      diabetes in the mixed ancestry population from South Africa.
AB  - BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARG),
      Pro12Ala and the insulin receptor substrate (IRS1), Gly972Arg confer opposite
      effects on insulin resistance and type 2 diabetes mellitus (T2DM). We
      investigated the independent and joint effects of PPARG Pro12Ala and IRS1
      Gly972Arg on markers of insulin resistance and T2DM in an African population with
      elevated risk of T2DM. In all 787 (176 men) mixed-ancestry adults from the
      Bellville-South community in Cape Town were genotyped for PPARG Pro12Ala and IRS1
      Gly972Arg by two independent laboratories. Glucose tolerance status and insulin
      resistance/sensitivity were assessed. RESULTS: Genotype frequencies were 10.4%
      (PPARG Pro12Ala) and 7.7% (IRS1 Gly972Arg). Alone, none of the polymorphisms
      predicted prevalent T2DM, but in regression models containing both alleles and
      their interaction term, PPARG Pro12 conferred a 64% higher risk of T2DM.
      Furthermore PPARG Pro12 was positively associated in adjusted linear regressions
      with increased 2-hour post-load insulin in non-diabetic but not in diabetic
      participants. CONCLUSION: The PPARG Pro12 is associated with insulin resistance
      and this polymorphism interacts with IRS1 Gly972Arg, to increase the risk of T2DM
      in the mixed-ancestry population of South Africa. Our findings require
      replication in a larger study before any generalisation and possible application
      for risk stratification.

PMID- 24447397
TI  - Refractive change in the adult rabbit eye after corneal relaxation with the
      femtosecond laser.
AB  - BACKGROUND: A new procedure to correct myopia that does not disturb the cornea in
      the optical zone and avoids injuring the corneal epithelium could be a key
      advance in corneal refractive surgery. The aim of this study is to observe the
      refractive change in the adult rabbits undergoing femtosecond laser-assisted
      multilayer intrastromal ablation in the mid-periphery of the cornea without
      injury of epithelium. METHOD: The right eyes of 8 New Zealand White adult rabbits
      were used for the experiments. A 60-kHz femtosecond laser delivery system was
      used, and three lamellar layers of laser pulses were focused starting at a
      corneal depth of 180 MUm and ending at 90 MUm from the surface, with each
      successive layer placed 45 MUm anterior to the previous layer. In the interface
      of the applanation contact lens cone, a 6-mm diameter aluminum circle was placed
      at the center to block the laser, limiting ablation to the mid-periphery of the
      cornea. The laser settings were as follows: spot/line separation, 10 MUm;
      diameter, 8.0 mm; energy for ablating the stroma, 1.3 MUJ. An authorefractor was
      used to assess the manifest refraction. RESULTS: Mean spherical equivalent (SE)
      (mean +/- SD, SD: standard deviation) was significantly increased at
      postoperative week 1 (1.67 +/- 0.26 D, p < 0.0001), month 1 (1.65 +/- 0.23 D, p <
      0.0001), and month 3 (1.60 +/- 0.22 D, p < 0.0001) compared to baseline (0.68 +/-
      0.27 D). Mean spherical equivalent showed no significant change between
      postoperative week 1 and month 3 (p = 0.1168). CONCLUSION: Femtosecond laser
      assisted multilayer corneal intrastromal ablation in the mid-periphery may cause
      a consequent hyperopic shift with no refractive regression.

PMID- 24447398
TI  - Anncaliia algerae microsporidial myositis.
AB  - The insect microsporidian Anncaliia algerae was first described in 2004 as a
      cause of fatal myositis in an immunosuppressed person from Pennsylvania, USA. Two
      cases were subsequently reported, and we detail 2 additional cases, including the
      only nonfatal case. We reviewed all 5 case histories with respect to clinical
      characteristics, diagnosis, and management and summarized organism life cycle and
      epidemiology. Before infection, all case-patients were using immunosuppressive
      medications for rheumatoid arthritis or solid-organ transplantation. Four of the
      5 case-patients were from Australia. All diagnoses were confirmed by skeletal
      muscle biopsy; however, peripheral nerves and other tissues may be infected. The
      surviving patient received albendazole and had a reduction of immunosuppressive
      medications and measures to prevent complications. Although insects are the
      natural hosts for A. algerae, human contact with water contaminated by spores may
      be a mode of transmission. A. algerae has emerged as a cause of myositis,
      particularly in coastal Australia. 

PMID- 24447399
TI  - The establishment of evidence-based practice competencies for practicing
      registered nurses and advanced practice nurses in real-world clinical settings:
      proficiencies to improve healthcare quality, reliability, patient outcomes, and
      costs.
AB  - BACKGROUND: Although it is widely known that evidence-based practice (EBP)
      improves healthcare quality, reliability, and patient outcomes as well as reduces
      variations in care and costs, it is still not the standard of care delivered by
      practicing clinicians across the globe. Adoption of specific EBP competencies for
      nurses and advanced practice nurses (APNs) who practice in real-world healthcare
      settings can assist institutions in achieving high-value, low-cost evidence-based
      health care. AIM: The aim of this study was to develop a set of clear EBP
      competencies for both practicing registered nurses and APNs in clinical settings
      that can be used by healthcare institutions in their quest to achieve high
      performing systems that consistently implement and sustain EBP. METHODS: Seven
      national EBP leaders developed an initial set of competencies for practicing
      registered nurses and APNs through a consensus building process. Next, a Delphi
      survey was conducted with 80 EBP mentors across the United States to determine
      consensus and clarity around the competencies. FINDINGS: Two rounds of the Delphi
      survey resulted in total consensus by the EBP mentors, resulting in a final set
      of 13 competencies for practicing registered nurses and 11 additional
      competencies for APNs. LINKING EVIDENCE TO ACTION: Incorporation of these
      competencies into healthcare system expectations, orientations, job descriptions,
      performance appraisals, and clinical ladder promotion processes could drive
      higher quality, reliability, and consistency of healthcare as well as reduce
      costs. Research is now needed to develop valid and reliable tools for assessing
      these competencies as well as linking them to clinician and patient outcomes.

PMID- 24447400
TI  - Repair of tetralogy of Fallot in or beyond the fourth decade of life.
AB  - OBJECTIVE: Patients with tetralogy of Fallot (TOF) undergoing surgery in
      adulthood represent a challenge. We report our experience with such patients in
      or beyond the fourth decade of life. DESIGN: Retrospective cohort. SETTING:
      Multispeciality tertiary level referral center PATIENTS: Forty-one (age 30-52
      years) with TOF undergoing surgery between January 2002 and March 2013. The
      hospital records of these patients were analyzed. INTERVENTIONS: None. OUTCOME
      MEASURES: Early and late morbidity and mortality, duration of mechanical
      ventilatory support, inotropic score, intensive care unit and hospital stay, and
      correlation with various parameters. RESULTS: Significant aortopulmonary
      collaterals were present in 28 patients; these were occluded in cardiac
      catheterization laboratory prior to repair. Median intraoperative right:left
      ventricular pressure ratio was 0.40 (range 0.2-0.8). Median inotropic score was
      10 (range 5-30). Median duration of mechanical ventilation was 12 hours (range 6
      48 hours). Preoperative oxygen saturation was negatively correlated with
      inotropic score (P = .001, r = -0.485), mechanical ventilatory support (P = .003,
      r = -0.460), intensive care unit stay (P = .004, r = -0.442), and hospital stay
      (P = .028, r = -353). Inotropic score was higher in patients with aortopulmonary
      collaterals (n = 28, P = .03), high preoperative hematocrit (n = 29, P = .029),
      and with right ventricular dysfunction (n = 6, P = .05). Patients with right
      ventricular outflow tract gradient >80 mm Hg (n = 19) had prolonged hospital stay
      (P = .002). Patients undergoing pure transatrial repair (n = 24) showed lower
      inotropic score (P = .045), less intensive care unit (P = .04), and hospital stay
      (P = .031). There were two early and two late deaths (one from trauma and one
      from unknown etiology). Median follow-up was 42 months. Thirty-one patients were
      in New York Heart Association class II and six were in class III. CONCLUSION:
      Repair of TOF in and beyond the fourth decade of life is feasible with acceptable
      results. Patients with high hematocrit, lower oxygen saturation, right
      ventricular dysfunction, aortopulmonary collaterals, and high preoperative right
      ventricular outflow tract gradients have a prolonged postoperative course.

PMID- 24447401
TI  - The European Organization for Research and Treatment of Cancer quality of life
      questionnaire-BR23 Breast Cancer-Specific Quality of Life Questionnaire:
      psychometric properties in a Moroccan sample of breast cancer patients.
AB  - BACKGROUND: Quality of life (QOL) and its measurement in cancer patients is
      becoming increasingly important. Breast cancer diagnosis and treatment are often
      associated with psychological distress and reduced QoL. In Arabic-speaking
      countries, QoL of patients with cancer is inadequately studied.The aim of this
      study was to test the reliability and validity of the Moroccan Arabic version of
      the European Organization for Research and Treatment of Cancer (EORTC) Breast
      Cancer-Specific Quality of Life Questionnaire (QLQ-BR23). METHODS: After
      translation and cross-cultural adaptation, the questionnaire was tested on breast
      cancer patients. The participants' number for the test and the retest were 105
      and 37 respectively. Internal consistency was tested using Cronbach's alpha
      coefficient (alpha), the test-retest reliability using intraclass correlation
      coefficients (ICC). Construct validity was assessed by examining item-convergent
      and divergent validity. RESULTS: The questionnaire was administered to 105
      patients. The mean age of patients was 48 years (SD: 16), 62.9% were married.
      68.6% of all participants lived in urban area.The average time to complete the
      QLQ- BR23 was 15 min. Cronbach's alpha coefficient, were all >0.7, with the
      exception of breast symptoms and arm symptoms. All items exceeded the 0.4
      criterion for convergent validity except item 20 and 23 related to pain and skin
      problems in the affected breast respectively. CONCLUSION: In general, the
      findings of this study indicated that the Moroccan Arabic version of the EORTC
      QLQ-BR23 is a reliable and valid supplementary measure of the QOL in breast
      cancer patients and can be used in clinical trials and studies of outcome
      research in oncology.

PMID- 24447402
TI  - TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing
      vasculature?
AB  - AIMS: We sought to identify the determinants of orthostatic hypotension (OH)
      among patients referred to the transient ischaemic attack (TIA) clinic. METHODS:
      We conducted a retrospective analysis of prospectively collected data on patients
      who attended the TIA clinic in a UK hospital between January 2006 and September
      2009. Each patient had their supine and standing or sitting blood pressure
      measured. Logistic regression was used to estimate the univariate and
      multivariate odds of OH for the subgroups of patients based on their diagnosis. A
      10% significance level for the univariate analysis was used to identify variables
      in the multivariate model. RESULTS: A total of 3222 patients were studied of whom
      1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of
      either systolic or diastolic OH in the TIA, stroke and patients with other
      diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292),
      respectively. Multivariate analyses showed age, prior history of TIA, and
      diabetes were independently significantly associated with systolic OH alone or
      diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56
      (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the
      diagnosis of stroke, peripheral vascular disease (PVD) was significantly
      associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a
      significantly lower odds of OH (0.61, 0.42-0.88). In patients with other
      diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated
      with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH.
      CONCLUSION: Orthostatic hypotension is prevalent among patients presenting to TIA
      clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be
      a significant associate of OH in this patient population.

PMID- 24447403
TI  - TLR4 polymorphism is not associated with biopsy proven giant cell arteritis.
AB  - OBJECTIVES: Giant cell arteritis (GCA) is a systemic inflammatory vasculitis
      affecting the elderly. It primarily affects medium and large arteries of the head
      and neck and can cause stroke and blindness. The cause of GCA is unknown; however
      both genetic and environmental factors are likely to be involved. TLR4 is
      implicated in the pathogenesis of GCA, however previous studies, examining the
      association between GCA and two TLR4 single nucleotide polymorphisms (SNPs), have
      reported conflicting results. The aim of this study was to determine the
      association between GCA and range of SNPs spanning the TLR4 gene sequence.
      METHODS: A case-control genetic study was performed using DNA from Australian
      biopsy proven GCA patients (n=139) and population controls (n=130). Samples were
      genotyped for 8 SNPs tagging common variation across TLR4. These SNPs included
      rs4986790 (+896A/G, Asp299Gly) and rs4986791 (+1196C/T) which have been
      previously studied in GCA. Allelic and haplotypic variation was analysed by
      logistic regression assuming an additive genetic model. A random effects meta
      analysis of the association between GCA and rs4986790 was performed utilising
      data from three previous studies. RESULTS: rs4986790 and rs4986791 are in strong
      linkage disequilbrium and tag one of the five common TLR4 haplotypes identified.
      No associations were observed between TLR4 SNPs and/or haplotypes and GCA. A meta
      analysis, comprising 577 GCA patients and 1153 controls, did not confirm an
      association between GCA and rs4986790 (OR 1.29, 95% CI 0.86, 1.92, p=0.22).
      CONCLUSIONS: There is no evidence of an association between TLR4 polymorphism and
      susceptibility to GCA.

PMID- 24447404
TI  - Comparison of high-dose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for
      intermediate-risk prostate cancer.
AB  - OBJECTIVE: To compare tumour control and toxicity outcomes with the use of high
      dose intensity-modulated radiation therapy (IMRT) alone or brachytherapy combined
      with IMRT (combo-RT) for patients with intermediate-risk prostate cancer.
      PATIENTS AND METHODS: Between 1997 and 2010, 870 consecutive patients with
      intermediate-risk prostate cancer were treated at our institution with either
      86.4 Gy of IMRT alone (n = 470) or combo-RT consisting of brachytherapy combined
      with 50.4 Gy of IMRT (n = 400). Brachytherapy consisted of low-dose-rate
      permanent interstitial implantation in 260 patients and high-dose-rate temporary
      implantation in 140 patients. The median (range) follow-up for the entire cohort
      was 5.3 (1-14) years. RESULTS: For IMRT alone vs combo-RT, 7-year actuarial
      prostate-specific antigen (PSA)-relapse-free survival (PSA-RFS) rates were 81.4
      vs 92.0% (P < 0.001), and distant metastases-free survival (DMFS) rates were 93.0
      vs 97.2% (P = 0.04), respectively. Multivariate analysis showed that combo-RT was
      associated with better PSA-RFS (hazard ratio [HR], 0.40 [95% confidence interval,
      0.24-0.66], P < 0.001), and better DMFS (HR, 0.41 [0.18-0.92], P = 0.03). A
      higher incidence of acute genitourinary (GU) grade 2 (35.8 vs 18.9%; P < 0.01)
      and acute GU grade 3 (2.3 vs 0.4%; P = 0.03) toxicities occurred in the combo-RT
      group than in the IMRT-alone group. Most acute toxicity resolved. Late toxicity
      outcomes were similar between the treatment groups. The 7-year actuarial late
      toxicity rates for grade 2 gastrointestinal (GI) toxicity were 4.6 vs 4.1% (P =
      0.89), for grade 3 GI toxicity 0.4 vs 1.4% (P = 0.36), for grade 2 GU toxicity
      19.4 vs 21.2% (P = 0.14), and grade 3 GU toxicity 3.1 vs 1.4% (P = 0.74) for the
      IMRT vs the combo-RT group, respectively. CONCLUSIONS: Enhanced dose escalation
      using combo-RT was associated with superior PSA-RFS and DMFS outcomes for
      patients with intermediate-risk prostate cancer compared with high-dose IMRT
      alone at a dose of 86.4 Gy. While acute GU toxicities were more prevalent in the
      combo-RT group, the incidence of late GI and GU toxicities was similar between
      the treatment groups.

PMID- 24447405
TI  - Association between common genetic variants in the opioid pathway and smoking
      behaviors in Chinese men.
AB  - BACKGROUND: There is biological evidence that the brain opioidergic system plays
      a critical role in the addictive properties of nicotine. The purpose of the
      present study was to examine the associations of single nucleotide polymorphisms
      (SNPs) in the genes encoding mu-opioid receptor (MOR) and the MOR-interacting
      proteins (including OPRM1, ARRB2, and HINT1) with smoking behaviors in Chinese
      men. METHODS: A total of 284 subjects (including current and ex-smokers) were
      recruited. Special questionnaires were used to assess smoking behaviors including
      age of smoking initiation, daily cigarette consumption, and Fagerstrom test for
      nicotine dependence (FTND) score. Participant samples were genotyped for six SNPs
      in the opioid pathway genes: rs1799971 in OPRM1, rs1045280, rs2036657 and
      rs3786047 in ARRB2, rs3852209 and rs2278060 in HINT1. Linear and logistic
      regression models were used to determine single-locus and haplotype-based
      association analyses. RESULTS: There was no significant association between any
      of SNPs analyzed and smoking behaviors. Logistic regression analyses under
      dominant, recessive, and additive models showed no significant associations of
      the six SNPs with smoking status (current vs. ex-smokers). After adjustment for
      age at enrollment and smoking initiation age, HINT1 rs3852209 was significantly
      associated with smoking status with an OR of 0.54 (95% CI, 0.31-0.95; P = 0.03)
      under dominant inheritance model. No haplotypes in ARRB2 or HINT1 were related to
      smoking status. CONCLUSIONS: The present study indicates no significant
      association between common genetic variations in MOR and MOR-interacting proteins
      and smoking behaviors in Chinese men, and gives suggestive evidence that HINT1
      rs3852209 may be related to smoking status. The findings require confirmation
      from further studies in additional larger samples.

PMID- 24447406
TI  - Associations of metabolic syndrome and diabetes mellitus with 16-year survival
      after CABG.
AB  - BACKGROUND: The associations of metabolic syndrome (MetS) or diabetes mellitus
      (DM) on long-term survival after coronary artery bypass grafting (CABG) have not
      been extensively evaluated. The aim of the present study was to assess the impact
      of MetS and DM on the 16-year survival after CABG. METHODS: Diabetic and
      metabolic status together with relevant cardiovascular data was established in
      910 CABG patients operated in 1993-94. They were divided in three groups as
      follows: neither DM nor MetS (375 patients), MetS alone (279 patients) and DM
      with or without MetS (256 patients). The 16-year follow-up of patient survival
      was carried out using national health databases. The relative survival rates were
      analyzed using the Life Table method comparing the observed survival rates of
      three patient groups to the rates based on age-, sex- and time-specific life
      tables for the whole population in Finland. To study the independent significance
      of MetS and DM for clinical outcome, multivariate analysis was made using an
      optimizing stepwise procedure based on the Bayesian approach. RESULTS: Bayesian
      multivariate analysis revealed together six variables to predict clinical outcome
      (2 months to 16 years) in relation to the national background population, i.e.
      age, diabetes, left ventricular ejection fraction, BMI, perfusion time during the
      CABG and peripheral arterial disease. Our principal finding was that after
      postoperative period the 16-year prognosis of patients with neither DM nor MetS
      was better than that of the age-, sex-and time-matched background population
      (relative survival against background population 1.037, p < 0.0001). The overall
      survival of MetS patients resembled that of the matched background population
      (relative survival 0.998, NS). DM was associated with significantly increased
      mortality (relative survival 0.86, p < 0.0001). Additionally, mortality was even
      higher in patients receiving insulin treatment than in those without. Excess
      death rate of DM patients was predominantly caused by cardiovascular causes.
      CONCLUSION: In this long-term follow-up study patient groups without diabetes had
      at least equal 16 years' survival after CABG than their matched background
      populations. Survival of DM patients started to deteriorate already few years
      after the operation.

PMID- 24447407
TI  - Wilms tumor: experience of a hospital in southern Brazil.
AB  - BACKGROUND: Wilms tumor (WT) is the most common renal malignancy of childhood.
      The aim of this study was to verify the epidemiological profile and prognosis of
      a sample of patients from Brazil and compare them to similar data from other
      Latin American studies. METHOD: The sample consisted of consecutive patients
      diagnosed with WT in an oncohematology service of a referral hospital in Southern
      Brazil, between 1989 and 2009. Clinical, radiological, pathological and survival
      data were collected from the medical records. Analysis was done using Excel and
      SPSS version 18.0. The significance level was set at P < 0.05. RESULTS: The final
      sample consisted of 45 patients. The male/female ratio was 1.25:1. Mean age at
      diagnosis was 43.9 months and all patients were of European descent. Thirty-three
      patients (73.3%) had both signs/symptoms of abdominal mass and hypertension.
      Malformation was observed in nine patients (20%) and there was one case of
      Fanconi's anemia (2.2%). Three patients had bilateral disease (6.7%). The
      majority of patients had stage III and IV (62.2%). Patients with malformation had
      an earlier age at diagnosis (P = 0.018) and a higher prevalence of bilateral
      disease (P = 0.044). Overall survival was 75%. Age at diagnosis was the only
      significant independent predictor associated with death. CONCLUSION: Death is
      closely related to late diagnosis in WT. Oncologic services should also be
      concerned about morbidity caused by therapeutic options in cases of late
      diagnosis, and the consequences for quality of life.

PMID- 24447409
TI  - Congenital rubella syndrome in child of woman without known risk factors, New
      Jersey, USA.
AB  - We report a case of congenital rubella syndrome in a child born to a vaccinated
      New Jersey woman who had not traveled internationally. Although rubella and
      congenital rubella syndrome have been eliminated from the United States,
      clinicians should remain vigilant and immediately notify public health
      authorities when either is suspected. 

PMID- 24447408
TI  - Interplay of choline metabolites and genes in patient-derived breast cancer
      xenografts.
AB  - INTRODUCTION: Dysregulated choline metabolism is a well-known feature of breast
      cancer, but the underlying mechanisms are not fully understood. In this study,
      the metabolomic and transcriptomic characteristics of a large panel of human
      breast cancer xenograft models were mapped, with focus on choline metabolism.
      METHODS: Tumor specimens from 34 patient-derived xenograft models were collected
      and divided in two. One part was examined using high-resolution magic angle
      spinning (HR-MAS) MR spectroscopy while another part was analyzed using gene
      expression microarrays. Expression data of genes encoding proteins in the choline
      metabolism pathway were analyzed and correlated to the levels of choline (Cho),
      phosphocholine (PCho) and glycerophosphocholine (GPC) using Pearson's correlation
      analysis. For comparison purposes, metabolic and gene expression data were
      collected from human breast tumors belonging to corresponding molecular
      subgroups. RESULTS: Most of the xenograft models were classified as basal-like (N
      = 19) or luminal B (N = 7). These two subgroups showed significantly different
      choline metabolic and gene expression profiles. The luminal B xenografts were
      characterized by a high PCho/GPC ratio while the basal-like xenografts were
      characterized by highly variable PCho/GPC ratio. Also, Cho, PCho and GPC levels
      were correlated to expression of several genes encoding proteins in the choline
      metabolism pathway, including choline kinase alpha (CHKA) and
      glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5). These
      characteristics were similar to those found in human tumor samples. CONCLUSION:
      The higher PCho/GPC ratio found in luminal B compared with most basal-like breast
      cancer xenograft models and human tissue samples do not correspond to results
      observed from in vitro studies. It is likely that microenvironmental factors play
      a role in the in vivo regulation of choline metabolism. Cho, PCho and GPC were
      correlated to different choline pathway-encoding genes in luminal B compared with
      basal-like xenografts, suggesting that regulation of choline metabolism may vary
      between different breast cancer subgroups. The concordance between the metabolic
      and gene expression profiles from xenograft models with breast cancer tissue
      samples from patients indicates that these xenografts are representative models
      of human breast cancer and represent relevant models to study tumor metabolism in
      vivo.

PMID- 24447410
TI  - Thrifty metabolic programming in rats is induced by both maternal undernutrition
      and postnatal leptin treatment, but masked in the presence of both: implications
      for models of developmental programming.
AB  - BACKGROUND: Maternal undernutrition leads to an increased risk of metabolic
      disorders in offspring including obesity and insulin resistance, thought to be
      due to a programmed thrifty phenotype which is inappropriate for a subsequent
      richer nutritional environment. In a rat model, both male and female offspring of
      undernourished mothers are programmed to become obese, however postnatal leptin
      treatment gives discordant results between males and females. Leptin treatment is
      able to rescue the adverse programming effects in the female offspring of
      undernourished mothers, but not in their male offspring. Additionally, in these
      rats, postnatal leptin treatment of offspring from normally-nourished mothers
      programmes their male offspring to develop obesity in later life, while there is
      no comparable effect in their female offspring. RESULTS: We show by microarray
      analysis of the female liver transcriptome that both maternal undernutrition and
      postnatal leptin treatment independently induce a similar thrifty transcriptional
      programme affecting carbohydrate metabolism, amino acid metabolism and oxidative
      stress genes. Paradoxically, however, the combination of both stimuli restores a
      more normal transcriptional environment. This demonstrates that "leptin reversal"
      is a global phenomenon affecting all genes involved in fetal programming by
      maternal undernourishment and leptin treatment. The thrifty transcriptional
      programme was associated with pro-inflammatory markers and downregulation of
      adaptive immune mediators, particularly MHC class I genes, suggesting a deficit
      in antigen presentation in these offspring. CONCLUSIONS: We propose a revised
      model of developmental programming reconciling the male and female observations,
      in which there are two competing programmes which collectively drive liver
      transcription. The first element is a thrifty metabolic phenotype induced by
      early life growth restriction independently of leptin levels. The second is a
      homeostatic set point calibrated in response to postnatal leptin surge, which is
      able to over-ride the metabolic programme. This "calibration model" for the
      postnatal leptin surge, if applicable in humans, may have implications for
      understanding responses to catch-up growth in infants. Additionally, the
      identification of an antigen presentation deficit associated with metabolic
      thriftiness may relate to a previously observed correlation between birth season
      (a proxy for gestational undernutrition) and infectious disease mortality in
      rural African communities.

PMID- 24447411
TI  - Challenges to implementation of developmental screening in urban primary care: a
      mixed methods study.
AB  - BACKGROUND: Research is needed to identify challenges to developmental screening
      and strategies for screening in an urban pediatric setting. METHODS: Parents of
      young children and clinicians at four urban pediatric practices participated in
      focus groups prior to implementation of screening. Participants were queried
      regarding attitudes, social norms, and barriers to developmental screening. Using
      information from the focus groups, workflow strategies were developed for
      implementing screening. Referral rates and satisfaction with screening were
      gathered at the conclusion. RESULTS: Six focus groups of parents and clinicians
      were conducted. Major themes identified included 1) parents desired greater input
      on child development and increased time with physicians, 2) physicians did not
      fully trust parental input, 3) physicians preferred clinical acumen over
      screening tools, and 4) physicians lacked time and training to conduct screening.
      For the intervention, developmental screening was implemented at the 9-, 18-, 24
      , and 30-month well visits using the Ages & Stages Questionnaire-II and the
      Modified Checklist for Toddlers. 1397 (98% of eligible) children under 36 months
      old were enrolled, and 1184 (84%) were screened at least once. 1002 parents (85%)
      completed a survey at the conclusion of the screening trial. Most parents
      reported no difficulty completing the screens (99%), felt the screens covered
      important areas of child development (98%), and felt they learned about their
      child's strengths and limitations (88%). CONCLUSIONS: Developmental screening in
      urban low-income practices is feasible and acceptable, but requires strategies to
      capture parental input, provide training, facilitate referrals, and develop
      workflow procedures and electronic decision support.

PMID- 24447412
TI  - Facilitating women's access to misoprostol through community-based advocacy in
      Kenya and Tanzania.
AB  - OBJECTIVE: To explore the feasibility of educating communities about gynecologic
      uses for misoprostol at the community level through community-based organizations
      in countries with restrictive abortion laws. METHODS: In 2012, the Public Health
      Institute and Ipas conducted an operations research study, providing small grants
      to 28 community-based organizations in Kenya and Tanzania to disseminate
      information on the correct use of misoprostol for both abortion and postpartum
      hemorrhage. These groups were connected to pharmacies selling misoprostol. The
      primary outcomes of the intervention were reports from the community-based
      organizations regarding the health education strategies that they had developed
      and implemented to educate their communities. RESULTS: The groups developed
      numerous creative strategies to reach diverse audiences and ensure access to
      misoprostol pills. Given the restrictive environment, the groups attributed their
      success to having addressed the use of misoprostol for both indications (abortion
      and postpartum hemorrhage) and to using a harm reduction approach to frame the
      advocacy. CONCLUSION: This initiative proves that, even where abortion is legally
      restricted and socially stigmatized, community-based organizations can publicly
      and openly share information about misoprostol and refer it to women by using
      innovative and effective strategies, without political backlash. Furthermore, it
      shows that communities are eager for this information.

PMID- 24447413
TI  - Comparison of urine and self-collected vaginal samples for detecting human
      papillomavirus DNA in pregnant women.
AB  - OBJECTIVE: To investigate the utility of urine sampling for detecting human
      papillomavirus (HPV) DNA among pregnant women and to compare HPV DNA detection in
      urine with detection in vaginal samples. METHODS: In a cross-sectional study,
      urine and vaginal samples were self-collected from pregnant women attending
      prenatal care at Hospital Divina Providencia, Frederico Westphalen, Brazil,
      between October 2006 and August 2007. Part of the L1 region of the HPV genome was
      amplified via GP5(+)/bioGP6(+) primers. Positive urine was genotyped for high
      risk HPV genotypes (HPV16, HPV18, HPV31, HPV33, HPV39, HPV45, and HPV59).
      RESULTS: During the study period, urine samples were obtained from 133 pregnant
      women, 63 of whom also self-collected vaginal samples. HPV DNA was detected in
      54.0% (34/63) and 61.9% (39/63) of urine and vaginal samples, respectively. HPV
      infection was significantly associated with first intercourse at younger than 20
      years of age (P=0.008). There was substantial agreement in HPV DNA test results
      between the urine and vaginal samples (kappa value, 77.3%; P<0.0001). HPV31 and
      HPV16 accounted for 80.7% of the oncogenic types identified. CONCLUSION:
      Detection of HPV DNA in urine showed good agreement with detection in self
      collected vaginal samples, indicating that urine might be a reliable sample for
      HPV testing among pregnant women.

PMID- 24447414
TI  - Obstetric complications and cesarean delivery in Nepal.
AB  - OBJECTIVE: To determine the incidence of obstetric complications, the stillbirth
      rate, and the factors associated with cesarean delivery in central Nepal.
      METHODS: A community-based prospective cohort study was undertaken in the Kaski
      district during 2011-2012. In total, 701 women who were at least 5 months
      pregnant were recruited and interviewed. Participants were followed-up and
      interviewed again within 45 days after delivery. RESULTS: Of the 658 women who
      remained in the cohort after 43 were lost to follow-up, 12 (1.8%) had
      stillbirths. Cesareans accounted for 13.3% of the total deliveries. Age, urban
      residency, college-level education, and particularly presence of intrapartum
      symptoms significantly increased the likelihood of cesarean delivery. Prepartum,
      intrapartum, and postpartum symptoms were reported by 21.1%, 24.4%, and 10.2% of
      women, respectively. Common danger signs included prolonged labor, severe
      abdominal pain, swollen hand and body, and heavy bleeding. CONCLUSION: Obstetric
      complications and stillbirth rates were relatively high in central Nepal.
      Cesarean delivery appeared to meet obstetric need and was performed with medical
      indication, particularly after the onset of labor.

PMID- 24447415
TI  - Robotic technology for pelvic exenteration in cases of cervical cancer.
AB  - BACKGROUND: Cervical cancer represents one of the most common types of neoplasia
      among women; the use of minimally invasive techniques in the treatment of
      cervical cancer is a challenge. OBJECTIVES: To present evidence regarding robotic
      technology in the performance of pelvic exenteration in cases of cervical cancer.
      SEARCH STRATEGY: PubMed and Scopus databases were searched. SELECTION CRITERIA:
      Articles examining the use of robotic technology for pelvic exenteration in cases
      of cervical cancer were included. DATA COLLECTION AND ANALYSIS: Four studies were
      included. MAIN RESULTS: Most cancers treated with robotic-assisted pelvic
      exenteration were squamous cell carcinomas of the cervix. The stage of primary
      cancer ranged from IB2 to IVA. In 7 of the 8 patients, anterior pelvic
      exenteration was performed; the other patient underwent total pelvic
      exenteration. Procedure duration ranged from 375 to 600 minutes; blood loss was
      200-550 mL. Postoperative complications occurred in 2 of the 8 patients and
      included perineal abscess, Miami pouch fistula, and ureteral stenosis.
      Postoperative hospital stay ranged from 3 to 53 days, and postoperative follow-up
      ranged from 2 to 31 months. CONCLUSIONS: The gold standard for pelvic
      exenteration remains the open surgical approach; however, the application of
      robotic technology could be an alternate choice associated with excellent
      results.

PMID- 24447416
TI  - High-temperature high-pressure polymerized urethane dimethacrylate-mechanical
      properties and monomer release.
AB  - OBJECTIVE: This study was conducted to determine selected mechanical/physical
      properties of and monomer release from high-temperature high-pressure (HT/HP)
      polymerized urethane dimethacrylate (UDMA). METHODS: Flexural strength (sigmaf),
      hardness, fracture toughness (KIC), and density (rho) were determined for five
      UDMA resin blocks produced via different polymerization protocols. High
      performance liquid chromatography (HPLC) was used to determine monomer release
      from the five polymers. One way ANOVA, Scheffe multiple means comparisons
      (alpha=0.05), and Weibull statistics (for sigmaf) were used to analyze the
      results. RESULTS: The results showed that HT/HP polymerization resulted in a
      significant (p<0.05) increase in sigmaf and rho, along with an increase in
      Weibull modulus. No significant differences were found in hardness and KIC
      between the two HT/HP polymerized materials. A significantly lower (p<0.05)
      monomer release was detected for the HT/HP polymerized groups. SIGNIFICANCE: The
      results of this study suggest that HT/HP polymerization affects the network
      structure and leads to UDMA polymers with improved mechanical/physical properties
      and with dramatically reduced monomer release. The low elution of monomers from
      HT/HP and HP polymerized materials suggests the achievement of a higher degree of
      conversion and a lesser degree of inhomogeneity with regards to microgel domains.
      The results, however, cannot fully explain the dramatic increase in
      mechanical/physical properties reported previously for RCB, improvements that may
      be due to a better filler-matrix interaction afforded by HT/HP polymerization.

PMID- 24447417
TI  - Activity progression for anterior cruciate ligament injured individuals.
AB  - BACKGROUND: Functional exercises are important in the rehabilitation of anterior
      cruciate ligament deficient and reconstructed individuals but movement
      compensations and incomplete recovery persist. This study aimed to identify how
      tasks pose different challenges; and evaluate if different activities challenge
      patient groups differently compared to controls. METHODS: Motion and force data
      were collected during distance hop, squatting and gait for 20 anterior cruciate
      ligament deficient, 21 reconstructed and 21 controls. FINDINGS: Knee range of
      motion was greatest during squatting, intermediate during hopping and smallest
      during gait (P < 0.01). Peak internal knee extensor moments were greatest during
      distance hop (P < 0.01). The mean value of peak knee moments was reduced in
      squatting and gait (P < 0.01) compared to hop. Peak internal extensor moments
      were significantly larger during squatting than gait and peak external adductor
      moments during gait compared to squatting (P < 0.01). Fluency was highest during
      squatting (P < 0.01). All patients demonstrated good recovery of gait but
      anterior cruciate ligament deficient adopted a strategy of increased fluency (P <
      0.01). During squatting knee range of motion and peak internal knee extensor
      moment were reduced in all patients (P < 0.01). Both anterior cruciate ligament
      groups hopped a shorter distance (P < 0.01) and had reduced knee range of motion
      (P < 0.025). Anterior cruciate ligament reconstructed had reduced fluency (P <
      0.01). INTERPRETATION: Distance hop was most challenging; squatting and gait were
      of similar difficulty but challenged patients in different ways. Despite
      squatting being an early, less challenging exercise, numerous compensation
      strategies were identified, indicating that this may be more challenging than
      gait.

PMID- 24447418
TI  - Initial stability of an uncemented femoral stem with modular necks. An
      experimental study in human cadaver femurs.
AB  - BACKGROUND: Uncemented implants are dependent upon initial postoperative
      stability to gain bone ingrowth and secondary stability. The possibility to vary
      femoral offset and neck angles using modular necks in total hip arthroplasty
      increases the flexibility in the reconstruction of the geometry of the hip joint.
      The purpose of this study was to investigate and evaluate initial stability of an
      uncemented stem coupled to four different modular necks. METHODS: A cementless
      femoral stem was implanted in twelve human cadaver femurs and tested in a hip
      simulator with patient specific load for each patient corresponding to single leg
      stance and stair climbing activity. The stems were tested with four different
      modular necks; long, short, retro and varus. The long neck was used as reference
      in statistical comparisons. A micromotion jig was used to measure bone-implant
      movements, at two predefined levels. FINDINGS: A femoral stem coupled to a varus
      neck had the highest value of micromotion measured for stair climbing at the
      distal measurement level (60MUm). The micromotions measured with varus and retro
      necks were significantly larger than motions observed with the reference modular
      neck, P<0.001. INTERPRETATION: The femoral stem evaluated in this study showed
      acceptable micromotion values for the investigated loading conditions when
      coupled to modular necks with different lengths, versions and neck-shaft angles.

PMID- 24447419
TI  - Distinctive MRI features of the epileptogenic zone in children with tuberous
      sclerosis.
AB  - OBJECTIVE: Localization of the epileptogenic zone (EZ) is challenging in children
      with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI
      could identify the EZ in TSC patients independent of the clinical and diagnostic
      data. METHODS: Presurgical MRI's of 34 children with TSC who underwent epilepsy
      surgery at Miami Children's Hospital were retrospectively reevaluated by experts
      blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic
      changes) and abnormalities of the perituberal cortex typical of focal cortical
      dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle
      change, gray/white matter junction blurring) were identified and their
      localization was compared with the resection site. Sensitivity, specificity and
      accuracy of individual MRI features to localize the EZ were determined and
      statistically compared between postoperatively seizure-free and non-seizure-free
      patients as well as clusters of features typical of FCD and TSC. RESULTS: MRI
      alone correctly localized the resection cavity in all 19 postoperatively seizure
      free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity
      and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%,
      respectively) were superior to those typical of TCS (79%, 75% and 75%, p<0.0001).
      Increased cortical thickness and abnormal gyral formation outside tubers occurred
      only in the resection site. Resection sites were better predicted by MRI in
      seizure-free than in non-seizure-free patients. CONCLUSION: Thorough MRI
      evaluation identifies the EZ in a significant proportion of TSC patients.
      Epileptogenic regions were mostly characterized by "FCD-like" changes outside
      cortical tubers. The findings may have important practical consequences for
      surgical planning in TSC.

PMID- 24447420
TI  - Single-energy low-voltage arterial phase MDCT scanning increases conspicuity of
      adenocarcinoma of the pancreas.
AB  - PURPOSE: To test a single-energy low-voltage CT protocol for pancreatic
      adenocarcinoma. METHODS AND MATERIALS: A total of 30 patients with pathology
      proven pancreatic adenocarcinoma underwent 64-row MDCT with arterial phase at 80
      kV and were compared to a similar group of 30 patients scanned with a 120 kV
      protocol. Scans were compared for quantitative image parameters (attenuation and
      standard deviation in the pancreas, tumor, aorta), CTDI and DLP using an unpaired
      t-test. Image noise values for each protocol (SD of the psoas) were compared
      using an unpaired t-test. Effective dose was calculated for each protocol. CNR
      (=conspicuity/SDnoise) and FOM (CNR2/ED) were calculated. The Catphan600 phantom
      was used to evaluate image non-uniformity, noise, spatial resolution, and low
      contrast detectability. RESULTS: Mean patient weight was 68 kg in the study group
      and 73 kg in the control group (p=0.0355), while patient diameters at the celiac
      axis were not significantly different. Mean attenuation was significantly higher
      at 80 kV in the aorta (517.5+/-116.4 vs 290.3+/-76.4 HU) and normal pancreas
      (154.0+/-39.95 vs 90.02+/-19.01 HU) (all p<0.0001), while no significant
      difference was observed for adenocarcinoma (61.43+/-35.61 vs 47.45+/-18.95;
      p=n.s.). CTDI and DLP were significantly lower at 80 kV (6.00+/-0.90 mGy vs
      10.24+/-2.93 mGy, and 180.4+/-35.49 mGy cm vs 383.8+/-117 mGy cm, respectively;
      all p<0.0001). Tumor conspicuity (HUpancreas-HUtumor) was significantly higher at
      80 kV (94.2+/-39.3 vs 39.5+/-22 HU; p<0.0001). Mean image noise was significantly
      higher at 80kV (28.32+/-10.06 vs 19.7+/-7.1HU; p<0.0001). Effective dose was
      significantly lower at 80 kV (1.984+/-0.39 vs 5.75+/-1.75 mSv; p<0.0001). The
      total DLP for the exam was 1024+/-31.86 mGy cm for the 80 kV protocol and 1357+/
      62.60 mGy cm for the 120 kV protocol (p<0.0001). Phantoms showed higher non
      uniformity, slightly higher noise, slightly lower MTF (50%) and slightly higher
      percentage contrast for the 80 kV protocol. CONCLUSION: Single-source 80 kV
      pancreatic phase scanning results in higher conspicuity of pancreatic
      adenocarcinoma and FOM and in significant dose reduction while maintaining
      acceptable image quality.

PMID- 24447421
TI  - Anticlockwise swirl of mesenteric vessels: a normal CT appearance, retrospective
      analysis of 200 pediatric patients.
AB  - OBJECTIVE: The counterclockwise rotation of the SMV on SMA is a normal and non
      specific finding, which results in an incomplete swirl formation on CT scans.
      However, it has a potential to be misinterpreted as 'midgut volvulus' resulting
      in serious clinical implications. The study was done to determine the frequency
      and degree of counterclockwise rotation of the SMV on SMA on CT in normal
      otherwise asymptomatic pediatric patients undergoing CT scan. METHODS: In this
      IRB approved study, we retrospectively analyzed abdominal CT scan examinations of
      200 consecutive pediatric patients (age range of 11 days to 18 years), which were
      performed for different clinical indications over a period of 10 months. They
      were evaluated for the absence or presence and degree of counterclockwise
      rotation of the mesenteric vessels. RESULTS: Of the 200 patients, 128 (64%)
      patients showed no clockwise or anticlockwise rotation of mesenteric vessels.
      Counterclockwise rotation of SMV on SMA was seen in 72 (36%) patients. Further,
      the degree of rotation of vessels was also calculated, based on the criteria
      proposed by the authors. CONCLUSIONS: The counterclockwise rotation of SMV on SMA
      gives an appearance of mesenteric whirlpool in otherwise normal mesenteric
      vessels and can be misinterpreted as midgut volvulus. It is a normal CT
      appearance and is due to a variation in branching pattern of mesenteric vessels.
      Awareness of this normal branching pattern of mesenteric vessels is important to
      avoid an inadvertent laparotomy.

PMID- 24447422
TI  - Three modes of cardiac compressions in a single patient: a comparison of usual
      manual compressions, automated compressions, and open cardiac massage.

PMID- 24447423
TI  - Human antibody responses to avian influenza A(H7N9) virus, 2013.
AB  - Understanding host antibody response is crucial for predicting disease severity
      and for vaccine development. We investigated antibody responses against influenza
      A(H7N9) virus in 48 serum samples from 21 patients, including paired samples from
      15 patients. IgG against subtype H7 and neutralizing antibodies (NAbs) were not
      detected in acute-phase samples, but ELISA geometric mean titers increased in
      convalescent-phase samples; NAb titers were 20-80 (geometric mean titer 40).
      Avidity to IgG against subtype H7 was significantly lower than that against H1
      and H3. IgG against H3 was boosted after infection with influenza A(H7N9) virus,
      and its level in acute-phase samples correlated with that against H7 in
      convalescent-phase samples. A correlation was also found between hemagglutinin
      inhibition and NAb titers and between hemagglutinin inhibition and IgG titers
      against H7. Because of the relatively weak protective antibody response to
      influenza A(H7N9), multiple vaccinations might be needed to achieve protective
      immunity.

PMID- 24447424
TI  - Acute inactivation of the contralesional hemisphere for longer durations improves
      recovery after cortical injury.
AB  - A rapidly growing number of studies using inhibition of the contralesional
      hemisphere after stroke are reporting improvement in motor performance of the
      paretic hand. These studies have used different treatment onset time, duration
      and non-invasive methods of inhibition. Whereas these results are encouraging,
      several questions regarding the mechanisms of inhibition and the most effective
      treatment parameters are currently unanswered. In the present study, we used a
      rat model of cortical lesion to study the effects of GABA-mediated inactivation
      on motor recovery. In particular, we were interested in understanding better the
      effect of inactivation duration when it is initiated within hours following a
      cortical lesion. Cortical lesions were induced with endothelin-1 microinjections.
      The contralesional hemisphere was inactivated with continuous infusion of the
      GABA-A agonist Muscimol for 3, 7 or 14days in three different groups of animals.
      In a fourth group, Muscimol was infused at slower rate for 14days to provide
      additional insights on the relation between the effects of inactivation on the
      non-paretic forelimb behavior and the recovery of the paretic forelimb. In
      spontaneously recovered animals, the lesion caused a sustained bias to use the
      non-paretic forelimb and long-lasting grasping deficits with the paretic
      forelimb. Contralesional inactivation produced a general decrease of behavioral
      activity, affected the spontaneous use of the forelimbs and caused a specific
      reduction of the non-paretic forelimb function. The intensity and the duration of
      these behavioral effects varied in the different experimental groups. For the
      paretic forelimb, increasing inactivation duration accelerated the recovery of
      grasping function. Both groups with 14days of inactivation had similar recovery
      profiles and performed better than animals that spontaneously recovered. Whereas
      the plateau performance of the paretic forelimb correlated with the duration of
      contralesional inactivation, it was not correlated with the spontaneous use of
      the forelimbs or with grasping performance of the non-paretic hand. Our results
      support that contralesional inactivation initiated within hours after a cortical
      lesion can improve recovery of the paretic forelimb. In our model, increasing the
      duration of the inactivation improved motor outcomes but the spontaneous use and
      motor performance of the non-paretic forelimb had no impact on recovery of the
      paretic forelimb. 

PMID- 24447425
TI  - Effect of pegloticase on renal function in patients with chronic kidney disease:
      a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3
      clinical trials.
AB  - BACKGROUND: Pegloticase is approved in the US for treatment of refractory chronic
      gout. Since chronic kidney disease (CKD) is common in these patients, we
      conducted a post-hoc analysis of 2 replicate phase 3 trials and the subsequent
      open-label extension study to determine the effects of pegloticase on renal
      function in patients with CKD stages 3 and 4, as well as the effects of renal
      dysfunction on pegloticase efficacy and safety. FINDINGS: Patients with renal
      insufficiency were randomized to pegloticase 8 mg every 2 weeks (n = 42),
      pegloticase 8 mg every 4 weeks (n = 41), or placebo (n = 20) for 6 months as
      defined by the study protocols. Renal function was assessed by estimated
      glomerular filtration rate (eGFR). All patients completing the randomized trials
      could participate in an open-label extension study for a further 2.5 years. Uric
      acid response, the primary end point in the trials, was plasma uric acid <6.0
      mg/dl for 80% of months 3 and 6.Mean eGFR in both pegloticase dosing cohorts
      remained constant over the randomized treatment phase and long-term open-label
      extension study. The number of patients achieving uric acid response was similar
      across CKD stages (32% stage 1, 23% stage 2, 35% stage 3, and 39% stage 4,
      respectively, P = 0.3). There was no difference in the pegloticase safety profile
      based on CKD stage. CONCLUSIONS: Pegloticase treatment does not impact eGFR in
      CKD patients and response to pegloticase is independent of CKD stage. TRIAL
      REGISTRATION: Clinical trial identifier: NCT00325195.

PMID- 24447427
TI  - Combination therapy with anticoagulants, corticosteroids and intravenous
      immunoglobulin for women with severe obstetric antiphospholipid syndrome.

PMID- 24447426
TI  - The potential use of chickpeas in development of infant follow-on formula.
AB  - BACKGROUND: Undernutrition during childhood is a common disorder in the
      developing countries, however most research has focussed much on its treatment
      rather than its prevention. OBJECTIVE: We investigated the potential of using
      chickpeas in infant follow-on formula production against the requirements of
      WHO/FAO on complementary foods and EU regulations on follow-on formula. METHODS:
      Chickpeas were germinated for 72 hours followed by boiling, drying and dehulling
      in order to minimise associated anti-nutrition factors. Saccharifying enzymes
      were used to hydrolyse starch to maltose and the resulting flours were analysed
      for their protein content and amino acid profile. RESULTS: The protein content
      (percentage) increased from 16.66 +/- 0.35 and 20.24 +/- 0.50 to 20.00 +/- 0.15
      and 21.98 +/- 0.80 for the processed desi and kabuli cultivar compared to raw
      chickpeas, respectively (P < 0.05). There was insignificant change (P = 0.05) in
      amino acid profile following processing and the resulting flour was found to meet
      the amino acid requirements of WHO/FAO protein reference for 0-24 month's
      children. CONCLUSION: The designed chickpea based infant follow-on formula meets
      the WHO/FAO requirements on complementary foods and also the EU regulations on
      follow-on formula with minimal addition of oils, minerals and vitamins. It uses
      chickpea as a common source of carbohydrate and protein hence making it more
      economical and affordable for the developing countries without compromising the
      nutrition quality.

PMID- 24447428
TI  - Mobile phone text message reminders of antipsychotic medication: is it time and
      who should receive them? A cross-sectional trust-wide survey of psychiatric
      inpatients.
AB  - BACKGROUND: Poor adherence to antipsychotic medication is a widespread problem,
      and the largest predictor of relapse in patients with psychosis. Electronic
      reminders are increasingly used to improve medication adherence for a variety of
      medical conditions, but have received little attention in the context of
      psychotic disorders. We aimed to explore the feasibility and acceptability of
      including short message service (SMS) medication reminders in the aftercare plan
      of service users discharged from inpatient care on maintenance antipsychotic
      medication. METHODS: We conducted a cross-sectional, trust-wide survey in the
      inpatient units of the Oxleas National Health Service (NHS) Foundation Trust in
      the UK between June 29 and August 3, 2012. Using a self-report questionnaire and
      the Drug Attitude Inventory, we examined inpatient attitudes towards
      antipsychotic drugs, past adherence to antipsychotic medication, frequency of
      mobile phone ownership, and interest in receiving SMS medication reminders upon
      discharge from the ward. Predictors of a patient's interest in receiving
      electronic reminders were examined using simple logistic regression models.
      RESULTS: Of 273 inpatients, 85 met eligibility criteria for the survey, showed
      decisional capacity, and agreed to participate. Of the 85 respondents, over a
      third (31-35%) admitted to have forgotten to take/collect their antipsychotic
      medication in the past, and approximately half (49%) to have intentionally
      skipped their antipsychotics or taken a smaller dose than prescribed. Male
      patients (55%), those with negative attitudes towards antipsychotics (40%), and
      those unsatisfied with the information they received on medication (35%) were
      approximately 3 to 4 times more likely to report past intentional poor adherence.
      The large majority of respondents (80-82%) reported having a mobile phone and
      knowing how to use SMS, and a smaller majority (59%) expressed an interest in
      receiving SMS medication reminders after discharge. No variable predicted a
      patient's interest in receiving electronic reminders of antipsychotics.
      CONCLUSIONS: Automatic SMS reminders of antipsychotic medication were acceptable
      to the majority of the survey respondents as an optional service offered upon
      discharge from inpatient care. Automatic electronic reminders deserve further
      investigation as a flexible, minimally invasive, cost-effective and broadly
      applicable tool that can potentially improve antipsychotic adherence and clinical
      outcomes.

PMID- 24447429
TI  - The role of vitamin D in chronic obstructive pulmonary disease, asthma and other
      respiratory diseases.
AB  - There has been growing interest in recent years in the extraosseous effects of
      vitamin D. In this article, we review the physiology of vitamin D, the
      physiopathological effects associated with vitamin D deficit and the available
      evidence on its etiopathogenic role in respiratory diseases. Given the
      pleiotropic actions of vitamin D, it is biologically plausible that the deficit
      of this vitamin could play a pathogenic role of in the development of various
      respiratory diseases. However, the many epidemiological studies that have shown
      an association between low vitamin D levels and a higher risk of developing
      various respiratory diseases or a poorer prognosis if they do appear, were unable
      to show causality. Post-hoc analyses of some clinical trials, particularly in
      chronic obstructive pulmonary disease (COPD) and asthma, appear to suggest that
      some patient subtypes may benefit from correction of a vitamin D deficit. In this
      respect, it would be interesting to determine if the interindividual differences
      found in the effect of vitamin D deficit and responses to correcting this deficit
      could be explained by the genetic variants involved in vitamin D metabolism.
      Ultimately, only appropriately designed clinical trials will determine whether 25
      OHD supplements can prevent or improve the course of the various respiratory
      diseases in which an epidemiological association between prognosis and vitamin D
      deficit has been described.

PMID- 24447430
TI  - Prediction of bacterial type IV secreted effectors by C-terminal features.
AB  - BACKGROUND: Many bacteria can deliver pathogenic proteins (effectors) through
      type IV secretion systems (T4SSs) to eukaryotic cytoplasm, causing host diseases.
      The inherent property, such as sequence diversity and global scattering
      throughout the whole genome, makes it a big challenge to effectively identify the
      full set of T4SS effectors. Therefore, an effective inter-species T4SS effector
      prediction tool is urgently needed to help discover new effectors in a variety of
      bacterial species, especially those with few known effectors, e.g., Helicobacter
      pylori. RESULTS: In this research, we first manually annotated a full list of
      validated T4SS effectors from different bacteria and then carefully compared
      their C-terminal sequential and position-specific amino acid compositions,
      possible motifs and structural features. Based on the observed features, we set
      up several models to automatically recognize T4SS effectors. Three of the models
      performed strikingly better than the others and T4SEpre_Joint had the best
      performance, which could distinguish the T4SS effectors from non-effectors with a
      5-fold cross-validation sensitivity of 89% at a specificity of 97%, based on the
      training datasets. An inter-species cross prediction showed that T4SEpre_Joint
      could recall most known effectors from a variety of species. The inter-species
      prediction tool package, T4SEpre, was further used to predict new T4SS effectors
      from H. pylori, an important human pathogen associated with gastritis, ulcer and
      cancer. In total, 24 new highly possible H. pylori T4S effector genes were
      computationally identified. CONCLUSIONS: We conclude that T4SEpre, as an
      effective inter-species T4SS effector prediction software package, will help find
      new pathogenic T4SS effectors efficiently in a variety of pathogenic bacteria.

PMID- 24447432
TI  - Multidisciplinary management of pregnancy in complex congenital heart disease: a
      model for coordination of care.
AB  - With advancements in medical care, many women with complex congenital heart
      disease (CHD) are now living into adulthood and childbearing years. The strains
      of pregnancy and parturition can be dangerous in such patients, and careful
      interdisciplinary plans must be made to optimize maternal and fetal health
      through this process. Several large studies have been published regarding risk
      prediction and medical management of pregnancy in complex CHD, though few case
      studies detailing clinical care plans have been published. The objective of this
      report is to describe the process of developing a detailed pregnancy and delivery
      care plan for three women with complex CHD, including perspectives from the
      multidisciplinary specialists involved in the process. This article demonstrates
      that collaboration between specialists in the fields of cardiology,
      anesthesiology, high-risk obstetrics, maternal fetal medicine, and neonatology
      results in clinically successful individualized treatment plans for the
      management of pregnancy in complex CHD. Multidisciplinary collaboration is a
      crucial element in the management of pregnancy in complex CHD. We provide a
      template used in three cases which can serve as a model for the design of future
      care plans. 

PMID- 24447433
TI  - Recolonization of macrozoobenthos on defaunated sediments in a hypertrophic
      brackish lagoon: effects of sulfide removal and sediment grain size.
AB  - Influences of sediment types on recolonization of estuarine macrozoobenthos were
      tested using enclosures in a hypertrophic lagoon. Three types of azoic sediment,
      sand (S), sulfide-rich mud (M), and mud removed of sulfide through iron addition
      (MFe), were set in field for 35 days during a hypoxic period. A total of 14 taxa
      including opportunistic polychaetes and amphipods occurred. Infaunal community in
      S treatment was characterized by highest diversity, total density and biomass,
      and population density of five dominant taxa, while those parameters were lowest
      in M treatment. Sulfide removal in MFe treatment achieved much higher density,
      biomass, and population densities of several taxa in the sediment. Multivariate
      analyses demonstrated that the established community structure was unique to each
      treatment. These imply that dissolved sulfide level as well as sediment grain
      size is a key determinant for the community composition and recolonization speed
      of early colonists in estuarine soft-bottom habitats. 

PMID- 24447435
TI  - DNA based computing for understanding complex shapes.
AB  - This study deals with a computing method called DNA based computing (DBC) that
      takes inspiration from the Central Dogma of Molecular Biology. The proposed DBC
      uses a set of user-defined rules to create a DNA-like sequence from a given piece
      of problem-relevant information (e.g., image data) in a dry-media (i.e., in an
      ordinary computer). It then uses another set of user-defined rules to create an
      mRNA-like sequence from the DNA. Finally, it uses the genetic code to translate
      the mRNA (or directly the DNA) to a protein-like sequence (a sequence of amino
      acids). The informational characteristics of the protein (entropy, absence,
      presence, abundance of some selected amino acids, and relationships among their
      likelihoods) can be used to solve problems (e.g., to understand complex shapes
      from their image data). Two case studies ((1) fractal geometry generated shape of
      a fern-leaf and (2) machining experiment generated shape of the worn-zones of a
      cutting tool) are presented elucidating the shape understanding ability of the
      proposed DBC in the presence of a great deal of variability in the image data of
      the respective shapes. The implication of the proposed DBC from the context of
      Internet-aided manufacturing system is also described. Further study can be
      carried out in solving other complex computational problems by using the proposed
      DBC and its derivatives. 

PMID- 24447434
TI  - Phosphorylated p-70S6K predicts tamoxifen resistance in postmenopausal breast
      cancer patients randomized between adjuvant tamoxifen versus no systemic
      treatment.
AB  - INTRODUCTION: Activation of the phosphatidylinositol-3-kinase (PI3K) and/or
      mitogen-activated protein kinase (MAPK) pathways results in anti-estrogen
      resistance in vitro, but a biomarker with clinical validity to predict intrinsic
      resistance has not been identified. In metastatic breast cancer patients with
      previous exposure to endocrine therapy, the addition of a mammalian target of
      rapamycine (mTOR) inhibitor has been shown to be beneficial. Whether or not
      patients on adjuvant endocrine treatment might benefit from these drugs is
      currently unclear. A biomarker that predicts intrinsic resistance could
      potentially be used as companion diagnostic in this setting. We tested the
      clinical validity of different downstream-activated proteins in the PI3K and/or
      MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary
      breast cancer patients. METHODS: We recollected primary tumor tissue from
      patients who participated in a randomized trial of adjuvant tamoxifen (1-3 years)
      versus observation. After constructing a tissue micro-array, cores from 563
      estrogen receptor alpha positive were immunostained for p-AKT(Thr308), p
      AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for
      recurrence free interval were used to assess hazard ratios and interactions
      between these markers and tamoxifen treatment efficacy. RESULTS: Interactions
      were identified between tamoxifen and p-AKT(Thr308), p-mTOR, p-p70S6K and p
      ERK1/2. Applying a conservative level of significance, p-p70S6K remained
      significantly associated with tamoxifen resistance. Patients with p-p70S6K
      negative tumors derived significant benefit from tamoxifen (HR 0.24, P < 0.0001),
      while patients whose tumor did express p-p70S6K did not (HR = 1.02, P =0.95), P
      for interaction 0.004. In systemically untreated breast cancer patients, p-p70S6K
      was associated with a decreased risk for recurrence. CONCLUSIONS: Patients whose
      tumor expresses p-p70S6K, as a marker of downstream PI3K and/or MAPK pathway
      activation, have a favorable prognosis, but do not benefit from adjuvant
      tamoxifen. A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in
      these patients needs to be further explored.

PMID- 24447436
TI  - Medication prescription by nurses and the case of the Brazil: what can we learn
      from international research?

PMID- 24447437
TI  - Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in
      healthy children.
AB  - Seven-valent pneumococcal conjugate vaccine (PCV-7) is effective against vaccine
      serotype disease and carriage. Nevertheless, shifts in colonization and disease
      toward nonvaccine serotypes and other potential pathogens have been described. To
      understand the extent of these shifts, we analyzed nasopharyngeal microbial
      profiles of 97 PCV-7-vaccinated infants and 103 control infants participating in
      a randomized controlled trial in the Netherlands. PCV-7 immunization resulted in
      a temporary shift in microbial community composition and increased bacterial
      diversity. Immunization also resulted in decreased presence of the pneumococcal
      vaccine serotype and an increase in the relative abundance and presence of
      nonpneumococcal streptococci and anaerobic bacteria. Furthermore, the abundance
      of Haemophilus and Staphylococcus bacteria in vaccinees was increased over that
      in controls. This study illustrates the much broader effect of vaccination with
      PCV-7 on the microbial community than currently assumed, and highlights the need
      for careful monitoring when implementing vaccines directed against common
      colonizers. 

PMID- 24447438
TI  - Dietary trends and management of hyperphosphatemia among patients with chronic
      kidney disease: an international survey of renal care professionals.
AB  - OBJECTIVE: The objective of this study was to review the opinions and experiences
      of renal care professionals to examine dietary trends among patients with chronic
      kidney disease (CKD) and problems associated with the clinical management of
      hyperphosphatemia. DESIGN: This was an online survey comprising open and closed
      questions requesting information on patient dietary trends and the clinical
      management of hyperphosphatemia. The study was conducted in 4 European countries
      (the Netherlands, Spain, Sweden, and the United Kingdom). SUBJECTS: Participants
      were 84 renal care professionals. INTERVENTION: This was an online survey. MAIN
      OUTCOME MEASURE: Responder-reported experiences and perceptions of patient
      dietary trends and hyperphosphatemia management were assessed. RESULTS: Most
      survey responders (56%) observed an increase in the consumption of processed
      convenience food, 48% noticed an increase in the consumption of foods rich in
      phosphorus-containing additives, and 60% believed that there has been a trend of
      increasing patient awareness of the phosphorus content of food. Patients
      undergoing hemodialysis (HD) were most likely to experience difficulties in
      following advice on dietary phosphorus restriction (38% of responders estimated
      that 25-50% of their patients experienced difficulties, and 29% estimated that 51
      75% experienced difficulties). Maintaining protein intake and restricting dietary
      phosphorus were perceived as being equally important by at least half of
      responders for predialysis patients (56%) and for those undergoing peritoneal
      dialysis and HD (54% and 50%, respectively). There were international variations
      in dietary trends and hyperphosphatemia management. CONCLUSION: Although most
      responders have observed a trend of increasing awareness of the phosphorus
      content of food among patients with CKD, the survey results indicate that many
      patients continue to experience difficulties when attempting to restrict dietary
      phosphorus. The survey responses reflect the global trend of increasing
      consumption of processed convenience foods and phosphorus-containing additives,
      which has implications for the management of hyperphosphatemia in patients with
      CKD.

PMID- 24447439
TI  - Management of advanced primary urethral carcinomas.
AB  - Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of
      genitourinary cancers, with a predilection for men and African-Americans. The
      sites and histology of urethral carcinoma vary by gender and anatomical location.
      Squamous cell carcinoma is most common among both genders but adenocarcinomas are
      noted in 15-35% of cases among women. Obstructive or irritative symptoms and
      haematuria are common modes of presentation. Clinical evaluation includes
      cystourethroscopy with biopsy and examination under anaesthesia. Magnetic
      resonance imaging provides a highly effective method to image the primary tumour
      while defining the potential involvement of surrounding structures. Most tumours
      are localised, with regional metastases to nodal sites seen in up to 30% of cases
      in both genders, while distant metastases at presentation are rare (0-6%), but
      occur in up to 40% of cases with recurrent disease. Among men, the two most
      important prognostic factors are disease location and stage. Low-stage tumours
      (T1-2) and tumours involving the fossa navicularis or the penile urethra have a
      better prognosis than higher stage tumours (>T2 or N+) and lesions involving the
      bulbomembranous urethra. In women, in addition to stage and location, the size of
      the tumour has also prognostic implications. While surgery and radiation therapy
      (RT) are of benefit in early stage disease, advanced stage PUC requires
      multimodal treatment strategies to optimise local control and survival. These
      include induction chemotherapy followed by surgery or RT and concurrent
      chemoradiation with or without surgery. The latter strategy has been used
      successfully to treat other human papillomavirus-related cancers of the vagina,
      cervix and anus and may be of value in achieving organ preservation. Given the
      rarity of PUC, prospective multi-institutional studies are needed to better
      define the optimal treatment approach for this disease entity. 

PMID- 24447440
TI  - Response to commentary on a trial comparing krill oil versus fish oil.
AB  - Nichols et al. (Lipids Health Dis13:2, 2014) raised concern about the higher n-6
      concentration in fish oil used in our recent study which is different from
      typical commercial fish oils (Ramprasath et al. Lipids Health Dis12:178, 2013).
      The aim of our study was to compare the effect of consumption of similar amount
      of n-3 PUFA from krill and fish oil with placebo on plasma and RBC fatty acids.
      As the concentration of n-3 PUFA in the fish oil utilised was higher than that in
      krill oil, we deemed it important to keep consistent the concentration of n-3
      PUFA and volumes to be administered to participants between krill versus fish
      oils. As such, the fish oil used in the study was diluted with corn oil. Although
      the n-6 PUFA concentration in fish oil was higher compared to traditionally used
      fish oil, consumption of the fish oil used in our study actually reduced the
      total n-6 PUFA in plasma and RBC to a similar extent as did krill oil. Overall,
      our conclusion was that the increases in plasma and RBC concentrations of EPA and
      DHA along with improvement in the omega-3 index observed with consumption of
      krill oil compared with fish oil are due to differences in absorption and
      bioavailability based on the structural difference of the two oils rather than
      their n-6 PUFA content. 

PMID- 24447441
TI  - Certolizumab for rheumatoid arthritis.
AB  - This is a review of the pharmacology of certolizumab pegol and its efficacy and
      safety in the treatment of patients with rheumatoid arthritis refractory to
      synthetic disease-modifying anti-rheumatic drugs (DMARDs). Certolizumab is a new
      anti-TNF-alpha biologic agent injected subcutaneously with an innovative
      molecular structure and unique pharmacodynamic and pharmacokinetic properties.
      Data from controlled clinical trials indicate that the drug is effective in
      reducing disease activity and disability. It also inhibits radiographic
      progression. Certolizumab administration has an acceptable safety profile. The
      clinical data available suggest that the nature of adverse events is generally
      comparable to that of other TNF-alpha blockers. Given its rapid onset of action
      certolizumab presents an attractive alternative therapeutic option for patients
      with moderate to severe RA refractory to DMARDs. 

PMID- 24447442
TI  - Reducing the risk of false discovery enabling identification of biologically
      significant genome-wide methylation status using the HumanMethylation450 array.
AB  - BACKGROUND: The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA
      methylation of 485,512 CpGs in the human genome. The technology relies on
      hybridization of genomic fragments to probes on the chip. However, certain
      genomic factors may compromise the ability to measure methylation using the array
      such as single nucleotide polymorphisms (SNPs), small insertions and deletions
      (INDELs), repetitive DNA, and regions with reduced genomic complexity. Currently,
      there is no clear method or pipeline for determining which of the probes on the
      HM450K bead array should be retained for subsequent analysis in light of these
      issues. RESULTS: We comprehensively assessed the effects of SNPs, INDELs, repeats
      and bisulfite induced reduced genomic complexity by comparing HM450K bead array
      results with whole genome bisulfite sequencing. We determined which CpG probes
      provided accurate or noisy signals. From this, we derived a set of high-quality
      probes that provide unadulterated measurements of DNA methylation. CONCLUSIONS:
      Our method significantly reduces the risk of false discoveries when using the
      HM450K bead array, while maximising the power of the array to detect methylation
      status genome-wide. Additionally, we demonstrate the utility of our method
      through extraction of biologically relevant epigenetic changes in prostate
      cancer.

PMID- 24447443
TI  - Transcriptomics profiling and steroid production in mummichog (Fundulus
      heteroclitus) testes after treatment with 5alpha-dihydrotestosterone.
AB  - 5alpha-Dihydrotestosterone (DHT) is a potent androgen in mammals with multiple
      roles; however the physiological actions of DHT in male fishes are not well
      known. To address this knowledge gap, male mummichog (Fundulus heteroclitus) were
      continuously exposed to 0, 5, and 50 MUg/L DHT for 21 days. Following exposure,
      testes were separated for histology, ex vivo incubation to measure steroidogenic
      capacity, and gene expression analyses (real-time PCR and microarray). DHT
      significantly decreased ex vivo 11-ketotestosterone (11KT) production in males
      exposed to 50 MUg/L DHT but not 5 MUg/L DHT, and DHT exposure did not affect ex
      vivo testosterone production. Histological examination revealed that the amount
      of interlobular and connective tissue present in the testes was increased in the
      50 MUg/L DHT treatment. Despite reductions in the production of 11KT, DHT did not
      affect the expression of targeted genes in the steroidogenic pathway such as
      steroidogenic acute regulatory protein (star), P450 side chain cleavage (cyp11a1)
      and 11beta-hydroxysteroid dehydrogenase (hsd11b3). Microarray analysis in the
      testes of individuals from control and 50 MUg/L DHT revealed that males exposed
      to 50 MUg/L DHT showed regulated transcriptional sub-networks that were related
      to immunity, regulation of blood flow, lipids and xenobiotic clearance,
      suggesting that DHT may be involved in the physiological regulation of these
      processes in the fish testes. A second objective of this study was to determine
      the feasibility of measuring mRNA levels in tissues used for ex vivo steroid
      production by comparing RNA integrity and transcript levels in testes of both
      immediately flash frozen tissue and incubated tissue. There was no significant
      difference in RNA quality between the two time points, indicating RNA integrity
      can remain intact for at least 18 h in ex vivo assays, thereby providing a viable
      option for researchers assessing multi-level biological reproductive endpoints
      when limited tissue is available. While the gene expression levels of actb, efla,
      rps12, rps18, star, and hsd11b3 remained unchanged, esr2a (esrba), esr2b (esrbb)
      and cyp11a1 were significantly lower in incubated tissue compared to flash frozen
      tissue. Therefore caution must be used as the steady-state levels of select genes
      may change over time. This study improves our understanding of DHT action in the
      teleostean testis and generates new hypotheses regarding cell processes that are
      regulated by this underexplored and potent androgen.

PMID- 24447444
TI  - A framework for selecting analytical techniques in profiling authentic and
      counterfeit Viagra and Cialis.
AB  - Several analytical techniques aimed at profiling drugs are deemed costly and time
      consuming, and may not be promptly available for analysis when required. This
      paper proposes a method for identifying the analytical techniques providing the
      most relevant data for classification of drug samples into authentic and
      unauthentic categories. For that matter, we integrate principal components
      analysis (PCA) to k-Nearest Neighbor (KNN) and Support Vector Machine (SVM)
      classification tools. PCA is first applied to data from five techniques, i.e.,
      physical profile, X-ray fluorescence (XRF), direct infusion electrospray
      ionization mass spectrometry (ESI-MS), active pharmacological ingredients profile
      (ultra performance liquid chromatography, UPLC-MS), and infrared spectroscopic
      profile (ATR-FTIR). Subsets of PCA scores are then combined with a "leave one
      subset out at a time" approach, and the classification accuracy using KNN and SVM
      evaluated after each subset is omitted. Subsets yielding the maximum accuracy
      indicate the techniques to be prioritized in profiling applications. When applied
      to data from Viagra and Cialis, the proposed method recommended using the data
      from UPLC-MS, physical profile and ATR-FTIR techniques, which increased the
      categorization accuracy. In addition, the SVM classification tool is suggested as
      more accurate when compared to the KNN. 

PMID- 24447445
TI  - Real time quantitative colourimetric test for methamphetamine detection using
      digital and mobile phone technology.
AB  - The Simon presumptive color test was used in combination with the built-in
      digital camera on a mobile phone to detect methamphetamine. The real-time Red
      Green-Blue (RGB) basic color data was obtained using an application installed on
      the mobile phone and the relationship profile between RGB intensity, including
      other calculated values, and the colourimetric product was investigated. A wide
      linear range (0.1-2.5mg mL(-1)) and a low detection limit (0.0110+/-0.0001
      0.044+/-0.002mg mL(-1)) were achieved. The method also required a small sample
      size (20MUL). The results obtained from the analysis of illicit methamphetamine
      tablets were comparable to values obtained from gas chromatograph-flame
      ionization detector (GC-FID) analysis. Method validation indicated good intra-
      and inter-day precision (2.27-4.49%RSD and 2.65-5.62%RSD, respectively). The
      results suggest that this is a powerful real-time mobile method with the
      potential to be applied in field tests.

PMID- 24447446
TI  - Postmortem genetic screening of SNPs in RyR2 gene in sudden unexplained nocturnal
      death syndrome in the southern Chinese Han population.
AB  - To investigate the genetic variants of the RyR2 gene in sudden unexplained
      nocturnal death syndrome (SUNDS) in the southern Chinese Han population, we
      genetically screened 29 of the 105 coding exons of the RyR2 gene associated with
      catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic
      right ventricular cardiomyopathy (ARVC) in sporadic SUNDS victims using
      polymerase chain reaction (PCR) and direct sequencing methods. Genomic DNA was
      extracted from blood samples of 127 SUNDS cases and 165 healthy unrelated
      controls. None of the published or novel RyR2 missense mutations were found in
      127 SUNDS cases. A total of sixteen genetic variants of the RyR2 gene were
      identified, comprised of: one novel synonymous coding mutation (c.13710C>A), one
      novel synonymous rare polymorphism (c.14871C>T), and fourteen previously reported
      polymorphisms. The genotype and allele frequency of previously reported missense
      polymorphism c.5656G>A (G1886S) was of no statistical difference between SUNDS
      cases and controls (x(2)=0.390, P>0.05; x(2)=0.271, P>0.05). This is the first
      report of genetic phenotype of RyR2 gene of SUNDS in the southern Chinese Han
      population. Previously reported plausible pathogenic missense polymorphism G1886S
      may not be an independent predisposition factor of SUNDS in the southern Chinese
      Han population. The association of genetic variants of the RyR2 gene with SUNDS
      needs further elucidation. 

PMID- 24447447
TI  - Application of cross-ratio in traffic accident reconstruction.
AB  - Nowadays, video recording devices such as CCTV, digital cameras, mobile phones
      and car video recorders are ubiquitous. It becomes more and more frequent that
      traffic accident scenarios are captured by such video recording devices in one
      form or another. The present study focuses on the direct extraction of vehicle
      speeds from video footages by cross-ratio, a well known invariant under specific
      conditions in projective geometry. The minimum requirements for an accurate and
      direct determination of vehicle speed by cross-ratio are 2 image frames of the
      video footage containing the subject vehicle which by and large moves along a
      straight path from one frame to the other and the time lapsed between the 2 image
      frames are known. With the aid of a calibrated Doppler radar, a control study has
      been carried out to validate the method and determine the baseline uncertainty.
      The validated method has been applied to a small number of real world cases and
      the results are promising. Experimental results indicate that it is possible to
      extend its application in speed determination by a car camera. 

PMID- 24447448
TI  - Chemometric classification of casework arson samples based on gasoline content.
AB  - Detection and identification of ignitable liquids (ILs) in arson debris is a
      critical part of arson investigations. The challenge of this task is due to the
      complex and unpredictable chemical nature of arson debris, which also contains
      pyrolysis products from the fire. ILs, most commonly gasoline, are complex
      chemical mixtures containing hundreds of compounds that will be consumed or
      otherwise weathered by the fire to varying extents depending on factors such as
      temperature, air flow, the surface on which IL was placed, etc. While methods
      such as ASTM E-1618 are effective, data interpretation can be a costly bottleneck
      in the analytical process for some laboratories. In this study, we address this
      issue through the application of chemometric tools. Prior to the application of
      chemometric tools such as PLS-DA and SIMCA, issues of chromatographic alignment
      and variable selection need to be addressed. Here we use an alignment strategy
      based on a ladder consisting of perdeuterated n-alkanes. Variable selection and
      model optimization was automated using a hybrid backward elimination (BE) and
      forward selection (FS) approach guided by the cluster resolution (CR) metric. In
      this work, we demonstrate the automated construction, optimization, and
      application of chemometric tools to casework arson data. The resulting PLS-DA and
      SIMCA classification models, trained with 165 training set samples, have provided
      classification of 55 validation set samples based on gasoline content with 100%
      specificity and sensitivity. 

PMID- 24447449
TI  - Development and validation of an HPLC-DAD method for simultaneous determination
      of cocaine, benzoic acid, benzoylecgonine and the main adulterants found in
      products based on cocaine.
AB  - Here, an HPLC-DAD method was developed and validated for simultaneous
      determination of cocaine, two cocaine degradation products (benzoylecgonine and
      benzoic acid), and the main adulterants found in products based on cocaine
      (caffeine, lidocaine, phenacetin, benzocaine and diltiazem). The new method was
      developed and validated using an XBridge C18 4.6mm*250mm, 5MUm particle size
      column maintained at 60 degrees C. The mobile phase consisted of a gradient of
      acetonitrile and ammonium formate 0.05M - pH 3.1, eluted at 1.0mL/min. The volume
      of injection was 10MUL and the DAD detector was set at 274nm. Method validation
      assays demonstrated suitable sensitivity, selectivity, linearity, precision and
      accuracy. For selectivity assay, a MS detection system could be directly adapted
      to the method without the need of any change in the chromatographic conditions.
      The robustness study indicated that the flow rate, temperature and pH of the
      mobile phase are critical parameters and should not be changed considering the
      conditions herein determined. The new method was then successfully applied for
      determining cocaine, benzoylecgonine, benzoic acid, caffeine, lidocaine,
      phenacetin, benzocaine and diltiazem in 115 samples, seized in Brazil (2007
      2012), which consisted of cocaine paste, cocaine base and salt cocaine samples.
      This study revealed cocaine contents that ranged from undetectable to 97.2%, with
      97 samples presenting at least one of the degradation products or adulterants
      here evaluated. All of the studied degradation products and adulterants were
      observed among the seized samples, justifying the application of the method,
      which can be used as a screening and quantification tool in forensic analysis. 

PMID- 24447450
TI  - Differentiation of the 1-(methylenedioxyphenyl)-2-piperazinopropanes and 1
      (methoxyphenyl)-2-piperazinopropanones by GC-IRD and GC-MS.
AB  - Two amphetamine-like piperazine-containing compounds, 1-(3,4
      methylenedioxyphenyl)-2-piperazinopropane (3,4-MDPPP), its positional isomer 1
      (2,3-methylenedioxyphenyl)-2-piperazinopropane (2,3-MDPPP) and three
      methcathinone-like piperazine-containing regioisomeric ring substituted 1
      (methoxyphenyl)-2-piperazinopropanones (OMePPPOs) have identical elemental
      composition and no marked differences in their mass spectra. Perfluoroacylation
      of the secondary amine nitrogen of these isomeric piperazines gave mass spectra
      with differences in the relative abundance of some fragment ions but did not
      alter the fragmentation pathway to provide unique ions for discrimination among
      these isomers. Gas chromatography coupled to infrared detection (GC-IRD) provides
      direct confirmatory data for the identification of the carbonyl containing
      compounds and the differentiation of the 3,4-MDPPP from its direct (2,3-MDPPP)
      and indirect (OMePPPOs) regioisomers. The vapor phase infrared spectra provide
      for specific confirmation of each of the isomeric piperazines. The perfluoroacyl
      derivative forms of the five piperazines involved in this study were resolved on
      two stationary phases, the first is composed of 100% dimethyl polysiloxane (Rtx
      1) and the second of 5% diphenyl and 95% dimethyl polysiloxane (Rtx-5). 

PMID- 24447451
TI  - Investigation of the l-phenylacetylcarbinol process to substituted benzaldehydes
      of interest.
AB  - The large scale industrial manufacture of the nasal decongestant pseudoephedrine
      is typically carried out by the reductive amination of l-phenylacetylcarbinol (l
      PAC), which in turn is produced via the biotransformation of benzaldehyde using
      yeast. In recent years there has been increasing legislative control of the
      supply of pseudoephedrine due to it being diverted for the clandestine production
      of methylamphetamine and there is some evidence that a number of clandestine drug
      laboratory chemists have considered the application of the l-PAC process to
      manufacture their own pseudoephedrine. This work examined the use of a number of
      substituted benzaldehydes for the manufacture of the corresponding substituted l
      PAC analogue followed by reductive amination to the corresponding substituted
      pseudoephedrine/ephedrine analogues. These substituted pseudoephedrine/ephedrine
      analogues were either reduced or oxidised to determine the feasibility of
      producing the corresponding methylamphetamine or methcathinone analogues. As a
      result, the l-PAC process was identified as a viable route for synthesis of
      substituted methylamphetamines and methcathinones. 

PMID- 24447452
TI  - Detection of constitutive and inducible HSP70 proteins in formalin fixed human
      brain tissue.
AB  - The investigation of formalin fixed and paraffin embedded tissue is a routine
      method in forensic histology. Since these samples are usually stored for decades
      they provide a unique tissue bank for different scientific issues. In the past,
      numerous studies were conducted using different kinds of paraffin embedded
      tissues. However, it is well known that formalin affects macromolecules and thus
      might hamper reliable and reproducible molecular experiments. The aim of this
      study was to find out if the treatment with formalin has a negative effect on
      different protein detection methods and additionally to define the dimension of
      those possible deleterious effects. We incubated brain tissue samples in formalin
      for up to three months. After incubation, the samples were analyzed using
      immunohistochemistry (IHC) and Western blotting to specifically detect and
      quantify members of the HSP70 superfamily (heat shock proteins). Our study shows
      that the Western blot analysis of formalin fixed tissues does not allow a
      reliable detection of proteins at all, while a reproducible detection by IHC was
      still possible after one month of incubation. 

PMID- 24447453
TI  - Chemical analysis of pharmaceuticals and explosives in fingermarks using matrix
      assisted laser desorption ionization/time-of-flight mass spectrometry.
AB  - Chemical analysis of latent fingermarks, "touch chemistry," has the potential of
      providing intelligence or forensically relevant information. Matrix-assisted
      laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS) was
      used as an analytical platform for obtaining mass spectra and chemical images of
      target drugs and explosives in fingermark residues following conventional
      fingerprint development methods and MALDI matrix processing. There were two main
      purposes of this research: (1) develop effective laboratory methods for detecting
      drugs and explosives in fingermark residues and (2) determine the feasibility of
      detecting drugs and explosives after casual contact with pills, powders, and
      residues. Further, synthetic latent print reference pads were evaluated as mimics
      of natural fingermark residue to determine if the pads could be used for method
      development and quality control. The results suggest that artificial amino acid
      and sebaceous oil residue pads are not suitable to adequately simulate natural
      fingermark chemistry for MALDI/TOF MS analysis. However, the pads were useful for
      designing experiments and setting instrumental parameters. Based on the natural
      fingermark residue experiments, handling whole or broken pills did not transfer
      sufficient quantities of drugs to allow for definitive detection. Transferring
      drugs or explosives in the form of powders and residues was successful for
      preparing analytes for detection after contact with fingers and deposition of
      fingermark residue. One downfall to handling powders was that the analyte
      particles were easily spread beyond the original fingermark during development.
      Analyte particles were confined in the original fingermark when using transfer
      residues. The MALDI/TOF MS was able to detect procaine, pseudoephedrine, TNT, and
      RDX from contact residue under laboratory conditions with the integration of
      conventional fingerprint development methods and MALDI matrix. MALDI/TOF MS is a
      nondestructive technique which provides chemical information in both the mass
      spectra and chemical images. 

PMID- 24447454
TI  - Recovery and identification of bacterial DNA from illicit drugs.
AB  - Bacterial infections, including Bacillus anthracis (anthrax), are a common risk
      associated with illicit drug use, particularly among injecting drug users. There
      is, therefore, an urgent need to survey illicit drugs used for injection for the
      presence of bacteria and provide valuable information to health and forensic
      authorities. The objectives of this study were to develop a method for the
      extraction of bacterial DNA from illicit drugs and conduct a metagenomic survey
      of heroin and methamphetamine seized in the Australian Capital Territory during
      2002-2011 for the presence of pathogens. Trends or patterns in drug contamination
      and their health implications for injecting drug users were also investigated.
      Methods based on the ChargeSwitch((r))gDNA mini kit (Invitrogen), QIAamp DNA
      extraction mini kit (QIAGEN) with and without bead-beating, and an organic
      phenol/chloroform extraction with ethanol precipitation were assessed for the
      recovery efficiency of both free and cellular bacterial DNA. Bacteria were
      identified using polymerase chain reaction and electrospray ionization-mass
      spectrometry (PCR/ESI-MS). An isopropanol pre-wash to remove traces of the drug
      and diluents, followed by a modified ChargeSwitch((r)) method, was found to
      efficiently lyse cells and extract free and cellular DNA from Gram-positive and
      Gram-negative bacteria in heroin and methamphetamine which could then be
      identified by PCR/ESI-MS. Analysis of 12 heroin samples revealed the presence of
      DNA from species of Comamonas, Weissella, Bacillus, Streptococcus and
      Arthrobacter. No organisms were detected in the nine methamphetamine samples
      analysed. This study develops a method to extract and identify Gram-positive and
      Gram-negative bacteria from illicit drugs and demonstrates the presence of a
      range of bacterial pathogens in seized drug samples. These results will prove
      valuable for future work investigating trends or patterns in drug contamination
      and their health implications for injecting drug users as well as enabling
      forensic links between seizures to be examined. 

PMID- 24447455
TI  - Evidence evaluation in fingerprint comparison and automated fingerprint
      identification systems--Modeling between finger variability.
AB  - In the context of the investigation of the use of automated fingerprint
      identification systems (AFIS) for the evaluation of fingerprint evidence, the
      current study presents investigations into the variability of scores from an AFIS
      system when fingermarks from a known donor are compared to fingerprints that are
      not from the same source. The ultimate goal is to propose a model, based on
      likelihood ratios, which allows the evaluation of mark-to-print comparisons. In
      particular, this model, through its use of AFIS technology, benefits from the
      possibility of using a large amount of data, as well as from an already built-in
      proximity measure, the AFIS score. More precisely, the numerator of the LR is
      obtained from scores issued from comparisons between impressions from the same
      source and showing the same minutia configuration. The denominator of the LR is
      obtained by extracting scores from comparisons of the questioned mark with a
      database of non-matching sources. This paper focuses solely on the assignment of
      the denominator of the LR. We refer to it by the generic term of between-finger
      variability. The issues addressed in this paper in relation to between-finger
      variability are the required sample size, the influence of the finger number and
      general pattern, as well as that of the number of minutiae included and their
      configuration on a given finger. Results show that reliable estimation of between
      finger variability is feasible with 10,000 scores. These scores should come from
      the appropriate finger number/general pattern combination as defined by the mark.
      Furthermore, strategies of obtaining between-finger variability when these
      elements cannot be conclusively seen on the mark (and its position with respect
      to other marks for finger number) have been presented. These results immediately
      allow case-by-case estimation of the between-finger variability in an operational
      setting. 

PMID- 24447456
TI  - Lethal factor and anti-protective antigen IgG levels associated with inhalation
      anthrax, Minnesota, USA.
AB  - Bacillus anthracis was identified in a 61-year-old man hospitalized in Minnesota,
      USA. Cooperation between the hospital and the state health agency enhanced prompt
      identification of the pathogen. Treatment comprising antimicrobial drugs, anthrax
      immune globulin, and pleural drainage led to full recovery; however, the role of
      passive immunization in anthrax treatment requires further evaluation. 

PMID- 24447457
TI  - Seroepidemiology of chronic hepatitis B and C in the French Caribbean Island of
      Guadeloupe.
AB  - BACKGROUND: The prevalence of chronic hepatitis B and C was evaluated some twenty
      years ago among specific populations in Guadeloupe. The present study was
      designed to update these data and determine epidemiological features of chronic
      hepatitis B and C infections in the French Caribbean island of Guadeloupe.
      FINDINGS: The present study was carried out at the Sainte Genevieve Health and
      Prevention Center (Guadeloupe), between May 2006 and July 2007. This is a medical
      center where patients can attend a free medical check-up paid for by the Social
      Security system. Data on hepatitis B (HBV) and C (HCV) status and epidemiological
      factors were collected for this study.A total of 2,200 patients were included in
      the study. The prevalence of HBV surface antigen was 1.41% (95% CI: 1.0-2.0), and
      0.55% (95% CI: 0.28-0.96) for HCV. The vaccination rate against HBV was 42.0%.
      HBV transmission was associated with piercing (12.9%, p = 0.014) and familial
      exposure (6.4%, p < 0.001) and HCV transmission with gynecological surgery
      (50.0%, p = 0.01). The HBV profile was generally hepatitis B e antigen-negative
      (94.5%). No hepatitis delta was found. For HCV, genotype 1 was predominant (80%).
      CONCLUSIONS: This is the first study on the prevalence of HBV and HCV among a
      general clinic based population in Guadeloupe and the Caribbean islands. This
      study reveals that Guadeloupe is an area of low endemicity for HBV and low HCV
      prevalence. The reasons for these low prevalence rates are mainly related to the
      vaccination campaigns carried out during the past twenty years for HBV and the
      decrease of nosocomial transmission for HCV.

PMID- 24447458
TI  - Mechanical ventilation during extracorporeal membrane oxygenation.
AB  - The timing of extracorporeal membrane oxygenation (ECMO) initiation and its
      outcome in the management of respiratory and cardiac failure have received
      considerable attention, but very little attention has been given to mechanical
      ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have
      been shown to have an effect on survival and may also have contributed to a
      treatment effect in ECMO trials. Protective lung ventilation strategies
      established for non-ECMO-supported respiratory failure patients may not be
      optimal for more severe forms of respiratory failure requiring ECMO support. The
      influence of positive end-expiratory pressure on the reduction of the left
      ventricular compliance may be a matter of concern for patients receiving ECMO
      support for cardiac failure. The objectives of this review were to describe
      potential mechanisms for lung injury during ECMO for respiratory or cardiac
      failure, to assess the possible benefits from the use of ultra-protective lung
      ventilation strategies and to review published guidelines and expert opinions
      available on mechanical ventilation-specific management of patients requiring
      ECMO, including mode and ventilator settings. Articles were identified through a
      detailed search of PubMed, Ovid, Cochrane databases and Google Scholar.
      Additional references were retrieved from the selected studies. Growing evidence
      suggests that mechanical ventilation settings are important in ECMO patients to
      minimize further lung damage and improve outcomes. An ultra-protective
      ventilation strategy may be optimal for mechanical ventilation during ECMO for
      respiratory failure. The effects of airway pressure on right and left ventricular
      afterload should be considered during venoarterial ECMO support of cardiac
      failure. Future studies are needed to better understand the potential impact of
      invasive mechanical ventilation modes and settings on outcomes. 

PMID- 24447459
TI  - Promotion of a healthy lifestyle among 5-year-old overweight children: health
      behavior outcomes of the 'Be active, eat right' study.
AB  - BACKGROUND: This study evaluates the effects of an intervention performed by
      youth health care professionals on child health behaviors. The intervention
      consisted of offering healthy lifestyle counseling to parents of overweight (not
      obese) 5-year-old children. Effects of the intervention on the child having
      breakfast, drinking sweet beverages, watching television and playing outside were
      evaluated. METHODS: Data were collected with the 'Be active, eat right' study, a
      cluster randomized controlled trial among nine youth health care centers in the
      Netherlands. Parents of overweight children received lifestyle counseling
      according to the intervention protocol in the intervention condition (n = 349)
      and usual care in the control condition (n = 288). Parents completed
      questionnaires regarding demographic characteristics, health behaviors and the
      home environment at baseline and at 2-year follow-up. Cluster adjusted regression
      models were applied; interaction terms were explored. RESULTS: The population for
      analysis consisted of 38.1% boys; mean age 5.8 [sd 0.4] years; mean BMI SDS 1.9
      [sd 0.4]. There were no significant differences in the number of minutes of
      outside play or television viewing a day between children in the intervention and
      the control condition. Also, the odds ratio for having breakfast daily or
      drinking two or less glasses of sweet beverages a day showed no significant
      differences between the two conditions. Additional analyses showed that the odds
      ratio for drinking less than two glasses of sweet beverages at follow-up compared
      with baseline was significantly higher for children in both the intervention (p <
      0.001) and the control condition (p = 0.029). CONCLUSIONS: Comparison of the
      children in the two conditions showed that the intervention does not contribute
      to a change in health behaviors. Further studies are needed to investigate
      opportunities to adjust the intervention protocol, such as integration of
      elements in the regular well-child visit. The intervention protocol for youth
      health care may become part of a broader approach to tackle childhood overweight
      and obesity. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04965410.

PMID- 24447461
TI  - Three gene expression vector sets for concurrently expressing multiple genes in
      Saccharomyces cerevisiae.
AB  - Yeast has the potential to be used in bulk-scale fermentative production of fuels
      and chemicals due to its tolerance for low pH and robustness for autolysis.
      However, expression of multiple external genes in one host yeast strain is
      considerably labor-intensive due to the lack of polycistronic transcription. To
      promote the metabolic engineering of yeast, we generated systematic and
      convenient genetic engineering tools to express multiple genes in Saccharomyces
      cerevisiae. We constructed a series of multi-copy and integration vector sets for
      concurrently expressing two or three genes in S. cerevisiae by embedding three
      classical promoters. The comparative expression capabilities of the constructed
      vectors were monitored with green fluorescent protein, and the concurrent
      expression of genes was monitored with three different fluorescent proteins. Our
      multiple gene expression tool will be helpful to the advanced construction of
      genetically engineered yeast strains in a variety of research fields other than
      metabolic engineering. 

PMID- 24447460
TI  - Cost and outcome of behavioural activation versus cognitive behaviour therapy for
      depression (COBRA): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Cognitive behaviour therapy (CBT) is an effective treatment for
      depression. However, CBT is a complex therapy that requires highly trained and
      qualified practitioners, and its scalability is therefore limited by the costs of
      training and employing sufficient therapists to meet demand. Behavioural
      activation (BA) is a psychological treatment for depression that may be an
      effective alternative to CBT and, because it is simpler, might also be delivered
      by less highly trained and specialised mental health workers. METHODS/DESIGN:
      COBRA is a two-arm, non-inferiority, patient-level randomised controlled trial,
      including clinical, economic, and process evaluations comparing CBT delivered by
      highly trained professional therapists to BA delivered by junior professional or
      para-professional mental health workers to establish whether the clinical
      effectiveness of BA is non-inferior to CBT and if BA is cost effective compared
      to CBT. Four hundred and forty patients with major depressive disorder will be
      recruited through screening in primary care. We will analyse for non-inferiority
      in per-protocol and intention-to-treat populations. Our primary outcome will be
      severity of depression symptoms (Patient Health Questionnaire-9) at 12 months
      follow-up. Secondary outcomes will be clinically significant change and severity
      of depression at 18 months, and anxiety (General Anxiety Disorder-7
      questionnaire) and health-related quality of life (Short-Form Health Survey-36)
      at 12 and 18 months. Our economic evaluation will take the United Kingdom
      National Health Service/Personal Social Services perspective to include costs of
      the interventions, health and social care services used, plus productivity
      losses. Cost-effectiveness will explored in terms of quality-adjusted life years
      using the EuroQol-5D measure of health-related quality of life. DISCUSSION: The
      clinical and economic outcomes of this trial will provide the evidence to help
      policy makers, clinicians and guideline developers decide on the merits of
      including BA as a first-line treatment of depression. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN27473954.

PMID- 24447462
TI  - Facilitated brain delivery of poly (ethylene glycol)-poly (lactic acid)
      nanoparticles by microbubble-enhanced unfocused ultrasound.
AB  - Nanotechnology plays a unique instrumental role in the revolutionary development
      of brain-specific drug delivery, imaging, and diagnosis, but is highly limited by
      the existence of blood-brain barrier (BBB). In this study, microbubble-enhanced
      unfocused ultrasound (MEUUS) was developed as an approach to mediate an extensive
      brain delivery of poly (ethylene glycol) - poly (lactic acid) (PEG-PLA)
      nanoparticles. Following the MEUUS treatment, the nanoparticles signals were
      found to penetrate through the vascular walls and distributed deeply into the
      parenchyma at a significantly higher level (more than 250%) than those of the non
      MEUUS treated control. Such effect was reversible and dependent on nanoparticles
      injection timing, sonication mode and mechanical index. Together with the
      transmission electron microscopy analysis, the increased brain accumulation of
      nanoparticles was claimed to be largely mediated by an ultrasound-induced stable
      cavitation of the microbubble which resulted in mechanical stretching of the
      vessel wall and consequently induced cellular transcytosis of the nanoparticles.
      The MEUUS technique was also used to facilitate the brain delivery of PEG-PLA
      nanoparticles functionalized with amyloid beta-specific antibody 6E10 for
      enabling the recognition of the hallmarks of Alzheimer's disease that widely
      distributed in the brain. No erythrocytes extravasation and other visible damages
      in the brain were detected following the MEUUS treatment. These findings together
      indicated that unfocused ultrasound with the aid of microbubble could effectively
      improve the brain delivery of nanoparticles, and this approach might serve as a
      safe and flexible platform for the potential application of nanoparticles in the
      diagnosis and therapy of brain diseases. 

PMID- 24447463
TI  - A hydrogel-based tumor model for the evaluation of nanoparticle-based cancer
      therapeutics.
AB  - Three-dimensional (3D) tissue-engineered tumor models have the potential to
      bridge the gap between monolayer cultures and patient-derived xenografts for the
      testing of nanoparticle (NP)-based cancer therapeutics. In this study, a hydrogel
      derived prostate cancer (PCa) model was developed for the in vitro evaluation of
      doxorubicin (Dox)-loaded polymer NPs (Dox-NPs). The hydrogels were synthesized
      using chemically modified hyaluronic acid (HA) carrying acrylate groups (HA-AC)
      or reactive thiols (HA-SH). The crosslinked hydrogel networks exhibited an
      estimated pore size of 70-100 nm, similar to the spacing of the extracellular
      matrices (ECM) surrounding tumor tissues. LNCaP PCa cells entrapped in the HA
      matrices formed distinct tumor-like multicellular aggregates with an average
      diameter of 50 MUm after 7 days of culture. Compared to cells grown on two
      dimensional (2D) tissue culture plates, cells from the engineered tumoroids
      expressed significantly higher levels of multidrug resistance (MDR) proteins,
      including multidrug resistance protein 1 (MRP1) and lung resistance-related
      protein (LRP), both at the mRNA and the protein levels. Separately, Dox-NPs with
      an average diameter of 54 +/- 1 nm were prepared from amphiphilic block
      copolymers based on poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone)
      (PCL) bearing pendant cyclic ketals. Dox-NPs were able to diffuse through the
      hydrogel matrices, penetrate into the tumoroid and be internalized by LNCaP PCa
      cells through caveolae-mediated endocytosis and macropinocytosis pathways.
      Compared to 2D cultures, LNCaP PCa cells cultured as multicellular aggregates in
      HA hydrogel were more resistant to Dox and Dox-NPs treatments. Moreover, the NP
      based Dox formulation could bypass the drug efflux function of MRP1, thereby
      partially reversing the resistance to free Dox in 3D cultures. Overall, the
      engineered tumor model has the potential to provide predictable results on the
      efficacy of NP-based cancer therapeutics.

PMID- 24447464
TI  - Identification of novel 11beta-HSD1 inhibitors by combined ligand- and structure
      based virtual screening.
AB  - 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone to
      cortisol in a NADPH dependent manner. Overexpression of 11beta-HSD1 in key
      metabolic tissues is related to the development of type 2 diabetes, obesity,
      hypertension and metabolic syndrome. Using crystal structures of human 11beta
      HSD1 in complex with inhibitors as source of structural information, a combined
      ligand and structure-based virtual screening approach was implemented to identify
      novel 11beta-HSD1 inhibitors. A selected group of compounds was identified in
      silico and further evaluated in cell-based assays for cytotoxicity and 11beta
      HSD1 mediated cortisol production inhibitory capacity. The expression of 11beta
      HSD1 and 11beta-HSD2 in human LS14 adipocytes was assessed during
      differentiation. Biological evaluation of 39 compounds in adipocytes and steroids
      quantification by HPLC-MS/MS identify 4 compounds that exhibit 11beta-HSD1
      mediated cortisol production inhibitory activity with potencies in the micromolar
      range. Two compounds showed to be selective for the 11beta-HSD1 reductase
      activity and over 11beta-HSD2 isoform, and thus represent novel leads for the
      development of more active derivatives with higher efficacies targeting
      intracellular cortisol levels in type 2 diabetes and metabolic syndrome. 

PMID- 24447466
TI  - Novel paramyxovirus associated with severe acute febrile disease, South Sudan and
      Uganda, 2012.
AB  - In 2012, a female wildlife biologist experienced fever, malaise, headache,
      generalized myalgia and arthralgia, neck stiffness, and a sore throat shortly
      after returning to the United States from a 6-week field expedition to South
      Sudan and Uganda. She was hospitalized, after which a maculopapular rash
      developed and became confluent. When the patient was discharged from the hospital
      on day 14, arthralgia and myalgia had improved, oropharynx ulcerations had
      healed, the rash had resolved without desquamation, and blood counts and hepatic
      enzyme levels were returning to reference levels. After several known suspect
      pathogens were ruled out as the cause of her illness, deep sequencing and
      metagenomics analysis revealed a novel paramyxovirus related to rubula-like
      viruses isolated from fruit bats. 

PMID- 24447467
TI  - Practical observations on the performance of bare silica in hydrophilic
      interaction compared with C18 reversed-phase liquid chromatography.
AB  - The kinetic performance of a bare silica and C18 phase prepared from the same sub
      2MUm and 3.5MUm base materials were compared in the HILIC and RP mode using both
      charged and neutral solutes. The HILIC column was characterised using the neutral
      solute 5-hydroxymethyluridine, the weak base cytosine, and the strong base
      nortriptyline, the latter having sufficient retention also in the RP mode to
      allow comparison of performance. Naphthalene was also used as a simple neutral
      substance to evaluate the RP column alone. The retention factors of all
      substances were adjusted to give similar values (k'~5.5) at their respective
      optimum linear velocities. Reduced van Deemter b-coefficients (determined by
      curve fitting and by the peak parking method, using a novel procedure involving
      switching to a dummy column) were significantly lower in HILIC for all substances
      compared with those found under RP conditions. Against expectation, c
      coefficients were always lower in RP when compared with HILIC using sub-2MUm
      particles. While measurement of these coefficients is complicated by retention
      shifts caused by the influence of high pressure and by frictional heating
      effects, broadly similar results were obtained on larger particle (3.5MUm)
      phases. The mechanism of the separations was further investigated by examining
      the effect of buffer concentration on retention. It was concluded that HILIC can
      sometimes show somewhat inferior performance to RP for fast analysis at high
      mobile phase velocity, but clearly shows advantages when high column
      efficiencies, using longer columns at low flow velocity, are employed. The latter
      result is attributable to the lower viscosity of the mobile phase in HILIC and
      the reduced pressure requirement as well as the lower b-coefficients. 

PMID- 24447465
TI  - Astrocyte-derived growth factors and estrogen neuroprotection: role of
      transforming growth factor-alpha in estrogen-induced upregulation of glutamate
      transporters in astrocytes.
AB  - Extensive studies from the past decade have completely revolutionized our
      understanding about the role of astrocytes in the brain from merely supportive
      cells to an active role in various physiological functions including synaptic
      transmission via cross-talk with neurons and neuroprotection via releasing
      neurotrophic factors. Particularly, numerous studies have reported that
      astrocytes mediate the neuroprotective effects of 17beta-estradiol (E2) and
      selective estrogen receptor modulators (SERMs) in various clinical and
      experimental models of neuronal injury. Astrocytes contain two main glutamate
      transporters, glutamate aspartate transporter (GLAST) and glutamate transporter-1
      (GLT-1), that play a key role in preventing excitotoxic neuronal death, a process
      associated with most neurodegenerative diseases. E2 has been shown to increase
      expression of both GLAST and GLT-1 mRNA and protein and glutamate uptake in
      astrocytes. Growth factors such as transforming growth factor-alpha (TGF-alpha)
      appear to mediate E2-induced enhancement of these transporters. These findings
      suggest that E2 exerts neuroprotection against excitotoxic neuronal injuries, at
      least in part, by enhancing astrocytic glutamate transporter levels and function.
      Therefore, the present review will discuss proposed mechanisms involved in
      astrocyte-mediated E2 neuroprotection, with a focus on glutamate transporters. 

PMID- 24447468
TI  - Profiling gene expression to distinguish the likely active diazotrophs from a sea
      of genetic potential in marine sediments.
AB  - Nitrogen (N) cycling microbial communities in marine sediments are extremely
      diverse, and it is unknown whether this diversity reflects extensive functional
      redundancy. Sedimentary denitrifiers remove significant amounts of N from the
      coastal ocean and diazotrophs are typically regarded as inconsequential.
      Recently, N fixation has been shown to be a potentially important source of N in
      estuarine and continental shelf sediments. Analysis of expressed genes for
      nitrite reductase (nirS) and a nitrogenase subunit (nifH) was used to identify
      the likely active denitrifiers and nitrogen fixers in surface sediments from
      different seasons in Narragansett Bay (Rhode Island, USA). The overall diversity
      of diazotrophs expressing nifH decreased along the estuarine gradient from the
      estuarine head to an offshore continental shelf site. Two groups of sequences
      related to anaerobic sulphur/iron reducers and sulphate reducers dominated
      libraries of expressed nifH genes. Quantitative polymerase chain reaction (qPCR)
      and quantitative reverse transcription polymerase chain reaction (qRT-PCR) data
      shows the highest abundance of both groups at a mid bay site, and the highest
      nifH expression at the head of the estuary, regardless of season. Several
      potential environmental factors, including water temperature, oxygen
      concentration and metal contamination, may influence the abundance and nifH
      expression of these two bacterial groups.

PMID- 24447469
TI  - First versus second stage C/S maternal and neonatal morbidity: a systematic
      review and meta-analysis.
AB  - The rates of cesarean section at full cervical dilatation (second stage cesarean
      sections) are currently increasing. The purpose of the present study is to
      compare maternal and neonatal morbidity and mortality among cases offered
      cesarean section at full dilatation to those offered cesarean section prior to
      full dilatation. We searched Medline, Scopus, Clinicaltrials.org, Popline,
      Cochrane CENTRAL, and Google Scholar search engines, along with reference lists
      from all included studies. The RevMan 5.0 software was used for all analyses.
      Primary maternal outcomes were defined as death, ICU admission and need for
      transfusion, while primary neonatal outcomes were defined as death, neonatal unit
      admission and 5min Apgar score less than 7. Ten studies were finally retrieved
      involving 23,104 singleton childbearing women (18,160 operated in the first stage
      and 4944 in the second stage of labor). Second stage cesarean section seems to
      lead to higher maternal admissions to ICU (OR 7.41, 95% CI 2.47-22.5) and higher
      transfusion rates (OR 2.60, 95% CI 1.49-2.54). Neonatal death rates were also
      increased (OR 5.20, 95% CI 2.49-10.85) along with admissions to neonatal unit (OR
      1.63, 95% CI 0.91-2.91) and rates of Apgar score less than 7 in 5min (OR 2.77,
      95% CI 1.02-7.50). Second stage cesarean section seems to result significantly
      increased morbidity for both mothers and neonates. It seems that a direct
      evaluation with forceps and vacuum extractors is imperative in order to establish
      its place in modern evidence-based practice. 

PMID- 24447470
TI  - Effect of oxytocin treatment on explant size, plasma and peritoneal levels of MCP
      1, VEGF, TNF-alpha and histopathological parameters in a rat endometriosis model.
AB  - OBJECTIVE: To determine the effects of oxytocin (OT) on surgically induced
      endometriosis in a rat model. STUDY DESIGN: Twelve female Sprague-Dawley rats
      were included. After the implantation and establishment of autologous endometrium
      onto the abdominal wall peritoneum, the rats were randomly divided into two
      groups, treated with intramuscular oxytocin (OT group, 160MUgkg/day, n=6) or
      isotonic NaCl solution (control group, 1mLkg/day, n=6) for 28 days. To evaluate
      the therapeutic effects of OT, the explant volumes were calculated and the levels
      of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and
      TNF-alpha were measured in plasma and peritoneal fluid. Endometriotic explants
      were examined histologically by semiquantitative analysis. RESULTS: After
      treatment, the mean endometriotic explant volume was decreased in the OT group
      (p=0.016). The histopathological score and VEGF immunoexpression of endometriotic
      explants were significantly lower in the OT group (p=0.007) than in controls
      (p=0.000). Inflammatory cytokine levels in plasma and peritoneal fluid were
      considerably decreased in the OT group. Moreover, TUNEL immunohistochemistry
      clearly demonstrated more apoptotic changes in the mononuclear cells of the OT
      group compared with controls. CONCLUSION: We suggest that oxytocin might be
      considered as a potential candidate therapeutic agent for endometriosis.

PMID- 24447471
TI  - Postoperative nomogram to predict cancer-specific survival after radical
      nephroureterectomy in patients with localised and/or locally advanced upper tract
      urothelial carcinoma without metastasis.
AB  - OBJECTIVE: To propose and validate a nomogram to predict cancer-specific survival
      (CSS) after radical nephroureterectomy (RNU) in patients with pT1-3/N0-x upper
      tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: The international and
      the French national collaborative groups on UTUC pooled data from 3387 patients
      treated with RNU. Only 2233 chemotherapy naive pT1-3/N0-x patients were included
      in the present study. The population was randomly split into the development
      cohort (1563) and the external validation cohort (670). To build the nomogram,
      logistic regressions were used for univariable and multivariable analyses.
      Different models were generated. The most accurate model was assessed using
      Harrell's concordance index and decision curve analysis (DCA). Internal
      validation was then performed by bootstrapping. Finally, the nomogram was
      calibrated and externally validated in the external dataset. RESULTS: Of the 1563
      patients in the nomogram development cohort, 309 (19.7%) died during follow-up
      from UTUC. The actuarial CSS probability at 5 years was 75.7% (95% confidence
      interval [CI] 73.2-78.6%). DCA revealed that the use of the best model was
      associated with benefit gains relative to prediction of CSS. The optimised
      nomogram included only six variables associated with CSS in multivariable
      analysis: age (P < 0.001), pT stage (P < 0.001), grade (P < 0.02), location (P <
      0.001), architecture (P < 0.001) and lymphovascular invasion (P < 0.001). The
      accuracy of the nomogram was 0.81 (95% CI, 0.78-0.85). Limitations included the
      retrospective study design and the lack of a central pathological review.
      CONCLUSION: An accurate postoperative nomogram was developed to predict CSS after
      RNU only in locally and/or locally advanced UTUC without metastasis, where the
      decision for adjuvant treatment is controversial but crucial for the oncological
      outcome.

PMID- 24447473
TI  - Detection of branch retinal artery occlusions in Susac's syndrome.
AB  - BACKGROUND: We report an interesting case of asymptomatic retinal involvement in
      an encephalopathic patient enabling early identification of Susac's syndrome.
      CASE PRESENTATION: A 39-year-old Caucasian lady with hearing loss and
      encephalopathy was referred for ophthalmic assessment, including screening for
      branch retinal artery occlusions characteristic of Susac's syndrome. Clinical
      features included severe headaches, right-sided hypoacusis, dysphasia and poor
      memory. Routine blood tests were normal. MRI brain showed numerous hyperintense
      lesions mainly in corpus callosum. Although she was visually asymptomatic,
      dilated funduscopy detected bilateral multiple peripheral branch retinal artery
      occlusions which were confirmed on fluorescein angiography. She was subsequently
      started on intravenous steroids and pulsed cyclophosphamide which improved her
      symptoms within 48 hours. Full recovery was made with no new arterial occlusions
      on four months follow-up. CONCLUSION: The case further establishes the crucial
      role of a detailed ophthalmic examination supported by fluorescein angiography in
      the assessment of these patients, who are at risk of being misdiagnosed and
      undertreated.

PMID- 24447474
TI  - [Relationship between genetic polymorphism of long non-coding RNA and cancer
      susceptibility].

PMID- 24447475
TI  - [Effects of the Chinese herbal extract Songyou Yin on the residual hepatocellular
      carcinoma after chemotherapy in nude mice].
AB  - OBJECTIVE: To investigate the effects of a Chinese herbal extract Songyou Yin on
      residual hepatocellular carcinoma after chemotherapy in nude mice and the
      relevant mechanisms. METHODS: Orthotopic nude mouse models bearing residual
      hepatocellular carcinoma after chemotherapy was established using human liver
      carcinoma MHCC97L cells. Three different doses of Songyon Yin (2.1 g/kg, 4.2 g/kg
      and 8.4 g/kg) were administered to the mice in the trial groups by intragastric
      gavage, respectively. The mice in the control group were administered
      physiological saline. The tumor growth, metastasis and survival in the mice of
      each group were recorded. The corresponding mechanisms were studied. RESULTS: The
      pulmonary metastasis rates of the control group and 2.1g/kg, 4.2g/kg, 8.4g/kg
      Songyou Yin treatment group were 86.7%, 73.3%, 40.0%, and 20.0%, respectively,
      and the survivals of these groups were 53.83 +/- 4.71, 56.50 +/- 6.09, 66.67 +/-
      5.61, 81.17 +/- 7.36 days, respectively. Compared with the mice in the control
      group, mice in the 4.2 g/kg, 8.4 g/kg Songyou Yin treatment groups had a lower
      pulmonary metastasis rate (P = 0.021 and P = 0.001, respectively) and longer
      survival (P = 0.002 and P = 0.001, respectively). A restoration of E-cadherin
      expression and a concomitant reduction of N-cadherin expression were detected in
      the tumors of the 4.2 g/kg and 8.4 g/kg Songyou Yin treatment groups.
      CONCLUSIONS: Songyou Yin effectively inhibits the invasion and metastasis of the
      residual hepatocellular carcinoma after chemotherapy in nude mice through
      attenuating the epithelia-mesenchymal transition and prolongs the survival.
      Songyon Yin may have potential to promote the efficacy of chemotherapy in
      hepatocellular carcinoma.

PMID- 24447476
TI  - [Construction of RGD10-NGR9 dual-targeting superparamagnetic iron oxide and its
      magnetic resonance imaging features in nude mice].
AB  - OBJECTIVE: To construct angiogenesis-specific RGD10-NGR9 dual-targeting
      superparamagnetic iron oxide nanoparticles, and to evaluate its magnetic
      resonamce imaging (MRI) features in nude mice and potential diagnostic value in
      tumor MRI. METHODS: Dual-targeting peptides RGD10-NGR9 were designed and
      synthesized. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were
      synthesized by chemical co-precipitation method and the surface was modified to
      be hydrophilic by coating with dextran. The dual-targeting peptides RGD10-NGR9
      were conjugated to USPIO. Cell binding affinity and up-taking ability of the dual
      targeting USPIO nanoparticles to integrin alphanubeta3-APN positive cells were
      subsequently tested by Prussian blue staining and phenanthroline colorimetry in
      vitro. The RGD10-NGR9 conjugated with USPIO was injected intravenously into
      xenograft mice, which were scanned by MRI at predetermined time points. The MRI
      and contrast-to-noise ratio (CNR) values were calculated to evaluate the ability
      of dual-targeting USPIO as a potential contrast agent in nude mice. RESULTS: P
      CLN-Dextran-USPIO nanoparticles with stable physical properties were successfully
      constructed. The average diameter of Fe3O4 nanoparticles was 8-10 nm, that of
      Dextran-USPIO was about 20 nm and P-CLN-Dextran-USPIO had an average diameter
      about 30 nm. The in vitro studies showed a better specificity of dual-targeting
      USPIO nanoparticles on proliferating human umbilical vein endothelia cells
      (HUVEC). In vivo, RGD10-NGR9-USPIO showed a significantly reduced contrast in
      signal intensity and 2.83-times increased the CNR in the tumor MRI in xenograft
      mice. CONCLUSION: This novel synthesized RGD10-NGR9 dual-targeting USPIO is with
      better specific affinity in vitro and in vivo, and might be used as a molecular
      contrast agent for tumor angiogenesis MRI.

PMID- 24447477
TI  - [Inhibitory effect of a novel histone deacetylases inhibitor FK228 on human colon
      cancer HCT-116 cells in vitro and in vivo].
AB  - OBJECTIVE: To investigate the inhibitory effects of a novel histone deacetylases
      inhibitor FK228 on human colon cancer HCT-116 cells in vitro and in vivo, and
      evaluate its toxicity and side effects. METHODS: The in vitro growth inhibitions
      of HCT-116 cells by different concentrations of FK228 and 5-Fu for 24, 48 and 72
      h were assessed by CCK-8 assay. BALB/c nude mouse models of tumor xenografts were
      prepared by subcutaneous implantation of tumor tissue, and 4 mg/kg FK228 and 50
      mg/kg 5-Fu were i.p. injected, respectively. The inhibitory effects on tumor
      growth, hematology, and liver and kidney function were evaluated. RESULTS: CCK-8
      assay indicated that FK228 had an obvious growth inhibitory effect on HCT-116
      cells in a dose- and time-dependent manner. The IC50 of FK228 in HCT-116 cells
      was 12.05 ng/ml for 48 h, while the IC50 of 5-Fu was 18.92 ug/ml. At 20 days
      after FK228 and 5-Fu treatment, the tumor volume of the FK228 group was (139.71
      +/- 44.54)mm(3), significantly lower than that of the 5-Fu group [(282.28 +/-
      58.81)mm(3)] and that of the model group [(520.65 +/- 39.73)mm(3), P < 0.01 for
      both]. The average tumor weight was (0.07 +/- 0.02)g in the FK228 group,
      significantly lower than that of the 5-Fu group [(0.20 +/- 0.08)g, P < 0.01]. The
      tumor growth inhibition rate of the FK228 group was 73.2%, significantly higher
      than that of the 5-Fu group (45.8%, P < 0.01). The ALT levels of the FK228 and 5
      Fu groups were significantly higher than that of the model group (P < 0.01). The
      BUN of 5-Fu group was significantly higher than that of the model group (P <
      0.01), but the BUN of FK228 group was not significantly different from that of
      the blank and control groups (P > 0.05 for both). Routine blood test showed that
      WBC, RBC, Hb and PLT of the 5-Fu group were significantly lower than those of the
      model group (P < 0.05 for all), but only WBC of the FK228 group was significantly
      lower than that of the model group (P < 0.05). The pathological examination using
      HE staining revealed that in the FK228 group, there were fibrosis and
      inflammatory cell infiltration in the liver tissue, and mild edema of the renal
      tubules in the kidney. However, in the 5-Fu group there were extensive hepatocyte
      edema and necrosis in the liver, and evident deformation and necrosis of
      glomeruli and tubules, and tubular wall thinning in the kidney. CONCLUSIONS: The
      results of this study indicate that FK228 can more effectively than 5-Fu inhibit
      the growth of HCT-116 cells in vitro and vivo, and without obvious toxic effect
      on the kidney and hematology. Its clinical value in colon cancer treatment
      deserves further investigation.

PMID- 24447478
TI  - [Radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line
      A549].
AB  - OBJECTIVE: To explore the radiosensitizing effect of erlotinib on human lung
      adenocarcinoma cell line A549 cells and the related mechanisms. METHODS: The
      inhibitory effect of erlotinib on A549 cells was assessed by MTT assay, and its
      IC50 concentration was calculated. The radiosensitization was evaluated by the
      method of clone forming assay. Flow cytometry was used to analyze the effect of
      erlotinib on cell cycle and apoptosis. RESULTS: The growth of A549 cells was
      inhibited after the cells were exposed to erlotinib for 48 hours. Moreover, the
      inhibitory rates increased with the increase of erlotinib concentrations, and
      IC50 was 19.26 umol/L. In contrast to the irradiation alone group, the survival
      rates of the cells in erlotinib plus irradiation groups decreased, and erlotinib
      enhanced the radiosensitivity of the A549 cells. This effect was further
      increased as cells were exposed to erlotinib for a longer time. In the
      irradiation alone group and the two groups exposed to erlotinib for 24 hours and
      48 hours before irradiation, D0 values were 3.01 Gy, 2.58 Gy and 2.45 Gy
      respectively, and Dq values were 2.16 Gy, 1.94 Gy and 1.61 Gy, respectively. In
      the last two groups, SERD0 values were 1.17 and 1.23, respectively. The flow
      cytometry analysis showed that erlotinib induced G2/M phase arrest and increased
      the apoptosis rate in A549 cells. With the increase of exposure time, the effects
      were more significant. CONCLUSIONS: Erlotinib inhibits the A549 cell growth and
      enhances the radiosensitivity of A549 cells in vitro. The radiosensitizing
      mechanisms might be related to inhibiting repair of sublethal injury and inducing
      G2/M phase arrest and apoptosis.

PMID- 24447472
TI  - Acute and chronic effects of ethanol on learning-related synaptic plasticity.
AB  - Alcoholism is associated with acute and long-term cognitive dysfunction including
      memory impairment, resulting in substantial disability and cost to society. Thus,
      understanding how ethanol impairs cognition is essential for developing treatment
      strategies to dampen its adverse impact. Memory processing is thought to involve
      persistent, use-dependent changes in synaptic transmission, and ethanol alters
      the activity of multiple signaling molecules involved in synaptic processing,
      including modulation of the glutamate and gamma-aminobutyric acid (GABA)
      transmitter systems that mediate most fast excitatory and inhibitory transmission
      in the brain. Effects on glutamate and GABA receptors contribute to ethanol
      induced changes in long-term potentiation (LTP) and long-term depression (LTD),
      forms of synaptic plasticity thought to underlie memory acquisition. In this
      paper, we review the effects of ethanol on learning-related forms of synaptic
      plasticity with emphasis on changes observed in the hippocampus, a brain region
      that is critical for encoding contextual and episodic memories. We also include
      studies in other brain regions as they pertain to altered cognitive and mental
      function. Comparison of effects in the hippocampus to other brain regions is
      instructive for understanding the complexities of ethanol's acute and long-term
      pharmacological consequences. 

PMID- 24447479
TI  - [Effects of 5-Aza-dC on 5-Fu chemosensitivity by modulating TIP30 gene expression
      in human colorectal cancer cells].
AB  - OBJECTIVE: To investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC) on
      TIP30 gene expression and the relationship between TIP30 expression and the
      sensitivity to 5-fluouracil (5-Fu) in colorectal cancer cells. METHODS: The
      methylation profile of TIP30 gene in HCT116 colorectal cancer cells was
      determined by methylation-specific PCR. The levels of TIP30 mRNA and protein were
      determined by RT-PCR and Western blot after the 5-Aza-dC treatment. MTT assay was
      used to detect the chemosensitivity of HCT116 cells to 5-Fu. RESULTS: TIP30 gene
      displayed complete DNA methylation in the HCT116 cells without 5-Aza-dC
      pretreatment. After the 5-Aza-dC treatment for 3 days, only demethylating PCR
      amplification product was detected and TIP30 gene showed DNA demethylation. With
      the prolongation of the time of removal of 5-Aza-dC treatment, methylated and
      demethylated PCR amplification products were observed and TIP30 gene displayed
      both DNA methylation and DNA demethylation in the colorectal cancer cells. At the
      day 10 after removal of 5-Aza-dC, methylating PCR amplification product appeared
      and TIP30 gene showed DNA methylation. No expressions of TIP30 mRNA and protein
      were detected in the HCT116 cells untreated with 5-Aza-dC. After the treatment of
      5-Aza-dC for 3 d and then removed the 5-Aza-dC, the expressions of TIP30 mRNA and
      protein were increased obviously. With the prolonged time after 5-Aza-dC removal,
      the expressions of TIP30 mRNA and protein decreased and reached the lowest level
      on day 10. The IC50 values of 5-Fu were 41.62, 33.17 and 4.96 ug/ml in the HCT116
      cells pretreated with 5-Aza-dC, d0 and d10 with the drug removal after drug
      treatment for 3 d, respectively. CONCLUSIONS: The results of this study show that
      the expression of TIP30 gene may be associated with its DNA methylation status
      and may affect the sensitivity of colorectal cancer cells to 5-Fu.

PMID- 24447480
TI  - [Effect of downregulation of prostate cancer antigen-1 expression on malignant
      biological behavior of prostate cancer LNCaP cells].
AB  - OBJECTIVE: To detect the expression of prostate cancer antigen-1 (PCA-1) in
      prostate cancer, and to analyze the effects of downregulation of PCA-1 expression
      on malignant biological behavior of prostate cancer LNCaP cells, and to explore
      their possible molecular mechanisms. METHODS: PCA-1-siRNA and control siRNA were
      transfected into LNCaP cells with lipofectamine 2000. The cell cycle,
      proliferation and migration were determined by methyl thiazolyl tetrazolium (MTT)
      assay, flow cytometry and Transwell chambers, respectively. Western blotting was
      used to detect the expression of cyclin E, matrix metallopeptidase 9 (MMP-9) and
      p21. Immunohistochemistry was used to detect the expression of PCA-1 protein in
      126 cases of prostate cancer and 88 cases of benign prostatic hyperplasia (BPH).
      RESULTS: The positive rate of PCA-1 expression was 77.8% (98/126) in prostate
      cancer, and 10.2% (9/88) in BPH, and its expression was not significantly related
      to age, prostate specific antigen (PSA), Eastern Cooperative Oncology Group
      (ECOG) score (P > 0.05), and was associated with Gleason score, TNM staging and
      bone metastasis (P < 0.05). Downregulation of PCA-1 expression inhibited cell
      proliferation, arrested cell cycle at S phase and decreased cell migration of
      LNCaP cells. The downregulation of PCA-1 expression decreased the expression of
      Bcl-xl, cyclin E and MMP-9 proteins, but increased the expression of p21
      proteins. CONCLUSIONS: PCA-1 may play an important role in the development of
      prostate cancer. The downregulation of PCA-1 expression can lead to changes in
      the proliferation, cell cycle and migration of prostate cancer LNCaP cells, and
      these effects may be associated with the decrease of Bcl-xl, cyclin E and MMP-9
      proteins and increase of p21 protein.

PMID- 24447481
TI  - [Aberrant methylation of hMLH1 gene promoter in papillary thyroid cancer and its
      clinical significance].
AB  - OBJECTIVE: To investigate the aberrant promoter methylation of hMLH1 gene
      promoter and its clinical significance in papillary thyroid cancer (PTC).
      METHODS: methylation of hMLH1 gene promoter in the cancer tissue and matched
      tumor-adjacent normal tissue of 152 PTC patients were detected by real-time
      methylation specific PCR (qMSP). The relationship between the methylation of
      hMLH1 gene promoter and clinicopathological features was analyzed. RESULTS: The
      methylation rate of hMLH1 gene promoter in cancer tissues was 37.5% (57/152), of
      which 33 cases were totally methylated and 24 cases were partially methylated.
      The methylation rate of adjacent normal tissues was 5.3% (8/152)(all were
      partially methylated). The methylation rate of PTC tissues was significantly
      higher than that in the tumor-adjacent normal tissue (P < 0.01). The promoter
      methylation of hMLH1 gene in PTC was significantly correlated with age, size and
      number of the primary lesion, local invasion, T stage and lymph node metastasis
      (P < 0.05) , but not correlated with gender and clinical stage (P > 0.05).
      CONCLUSION: Promoter methylation of hMLH1 gene is a common molecular event in PTC
      tissue, and it is significantly correlated with the progression of PTC.

PMID- 24447482
TI  - [GRP78 expression in gastric cancer and its clinical significance].
AB  - OBJECTIVE: To investigate the clinical value of the expression of glucose
      regulated protein 78 (GRP78) for assessment of severity, chemoresistance and
      prognosis in patients with gastric adenocarcinoma ( GC) . METHODS: A cohort of
      237 patients with gastric cancer was included in this study. 160 patients of them
      were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78
      expression was detected by immunohistochemistry and 80 patients of them were
      tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay
      (ATP-TCA). In addition, the relationships were analyzed between GRP78 and age,
      gender, tumor differentiation, invasion, disease stage, lymph node metastasis and
      chemoresistance as well as disease-free survival (DFS). RESULTS: The positive
      rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the
      initiation of chemotherapy. The positive GRP78 expression was significantly
      correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph
      node metastasis (all P < 0.05), not correlated with gender and age, and high
      GRP78 expression was associated with the chemoresistance of the gastric cancer
      cells to chemotherapeutic agents. Negative GRP78 expression was associated with
      higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group
      and GRP78-negative group was (53.6 +/- 0.9) months and (38.3 +/- 0.8) months,
      respectively (P = 0.041). Interestingly, subgroup analysis revealed that the DFS
      in GRP78-negative and-positive patients treated with taxane-containing
      chemotherapy was (58.6 +/- 2.6) months and (49.1 +/- 2.7) months, respectively,
      but the difference was statistically not significant (P = 0.111). In contrast, in
      the subset of GRP78-negative and- positive patients treated with taxane
      containing regimens, the DFS was (45.5 +/- 1.9) months and (35.1 +/- 2.2) months,
      respectively, showing a significant difference (P = 0.038). In the group of
      patients with positive GRP78 expression, the patients treated with taxane
      containing chemotherapy had a longer DFS [(49.1 +/- 2.7) months] than those
      without that treatment [(35.1 +/- 2.2) months], showing a significant difference
      (P = 0.017). Univariate analysis revealed that DFS was correlated with
      histological grade, GRP78 expression and lymph node metastasis (all P < 0.05).
      Multivariate analysis showed that GRP78 expression and TNM staging were
      independent influencing factors for gastric cancer (both P < 0.05). CONCLUSIONS:
      The results of our study suggest that GRP78 may be a novel biomarker for
      assessment of malignant degree and prediction of chemoresistance in gastric
      cancer, and may be helpful to chemotherapy planning and prognosis prediction in
      patients with gastric cancer.

PMID- 24447483
TI  - [Expression of activin A in tissue and serum of patients with esophageal squamous
      cell carcinoma and its clinical significance].
AB  - OBJECTIVE: The aim of this study was to explore the expression of activin A in
      esophageal squamous cell carcinoma and its clinical significance. METHODS:
      Immunohistochemical (IHC) staining was used for detecting the expression of
      tissue activin A in sixty-four patients with esophageal squamous cell carcinoma,
      and enzyme-linked immunosorbent assay (ELISA) was used for detecting the serum
      activin A in the patients before and after surgery. The relationship between
      expression of activin A in the esophageal cancer tissue with clinicopathological
      features and its influence on prognosis were analyzed. RESULTS: The positive
      expression rate of activin A in esophageal squamous cell carcinoma was 82.8%
      (53/64), and that of normal esophageal epithelium was 6.7% (2/30), showing a very
      significant difference between them (P < 0.001). Expression of activin A was
      correlated with both lymph node metastasis and invasion depth of the tumor (all P
      < 0.05), and the expression of activin A was positively correlated with lymph
      node metastasis (r = 0.321, P < 0.05) and invasion depth of the tumor (r = 0.417,
      P < 0.05). The serum activin A of the patients before and after surgery was (911
      +/- 276) pg/ml and (667 +/- 236) pg/ml, respectively, showing a significant
      difference (P = 0.005). Univariate and multivariate analyses indicated that
      expression of activin A and lymph node metastasis were independent influencing
      factors for prognosis in patients with esophageal squamous cell carcinoma (all P
      < 0.05). CONCLUSIONS: Activin A may play an important role in the pathogenesis
      and development of esophageal squamous cell carcinoma, and it has an important
      reference value in the estimation of diagnosis and prognosis for esophageal
      squamous cell carcinoma.

PMID- 24447484
TI  - [Prognostic analysis of esophageal carcinoma patients with stump carcinoma and
      atypical hyperplasia after esophagectomy].
AB  - OBJECTIVE: To analyze the prognostic factors for esophageal carcinoma patients
      with stump carcinoma and atypical hyperplasia after esophagectomy. METHODS: From
      August 2006 to December 2010, 182 esophageal carcinoma patients with stump
      carcinoma and atypical hyperplasia after esophagectomy treated in our hospital
      were involved in this study, including 60 cases with grade I-II atypical
      hyperplasia, 23 cases with grade III atypical hyperplasia, 37 cases with
      carcinoma in situ, and 62 cases with invasive carcinoma. Prognostic factors for
      these patients were analyzed. RESULTS: The 1-, 2-, 3- and 4-year locoregional
      control rates of these 182 patients were 77.1%, 63.3%, 60.3% and 60.3%,
      respectively, and the over-all cumulative survival rates were 78.6%, 63.9%, 46.3%
      and 41.0%, respectively. A total of 56 cases suffered from locoregional
      recurrence (56/182, 30.8%), including anastomotic recurrence and lymph node
      metastasis. The number of locoregional recurrence patients of grade I-II of
      atypical hyperplasia was 13(13/60, 21.7%), grade III atypical hyperplasia and
      carcinoma in situ 21 (21/60, 35.0%), and invasive carcinoma 22 (22/62, 35.5%).
      There were no significant differences among the three groups(chi(2) = 3.485, P =
      0.175). There were significant differences in locoregional control rate and
      survival rate among the four treatment groups (P < 0.05). For patients with stump
      grade I~II atypical hyperplasia and different stage positive stump margin, the 1
      , 2-, 3- and 4-year survival rates of the four treatment groups had significant
      differences (P < 0.05). As for locoregional control rates, there were no
      significant differences in the four groups (P > 0.05). Univariate analysis showed
      that tumor length, depth of invasion, number of metastatic lymph nodes, number of
      lymph node metastatic fields, pTNM stage, stump pathological grade and treatment
      modality were main influencing factors for survival rate (P < 0.05);invasion
      depth, stump pathological grade and treatment modality were important factors for
      locoregional control. Multivariate Cox regression analysis showed that tumor
      length, number of metastatic lymph nodes, stump pathological grade and treatment
      modality were independent influencing factors for survival (all P <
      0.05);invasion depth, stump pathological grade and treatment modality were
      independent influencing factors for locoregional control (all P < 0.05).
      CONCLUSIONS: For the patients with stump carcinoma and atypical hyperplasia after
      esophagectomy, tumor length, number of metastatic lymph nodes, stump pathological
      grade and treatment modality are independent influencing factors for long-term
      survival, and invasion depth, stump pathological grade and treatment modality are
      independent influencing factors for locoregional control.

PMID- 24447485
TI  - [Clinical analysis of 34 patients with adrenal metastasis from breast cancer].
AB  - OBJECTIVE: To evaluate the clinical characteristics and prognosis of adrenal
      metastasis from breast cancer, and to explore methods to improve prognosis.
      METHODS: Thirty-four breast cancer patients with adrenal metastasis were
      diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was
      used for survival analysis. RESULTS: During the Jan. 1999 to Dec. 2010 period, 13
      595 patients with breast cancer were treated in our hospital. Among them, 34
      cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The
      median time to progression (TTP) and overall survival of the 34 patients was 6.2
      months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months),
      respectively. Eleven patients (34.4%) achieved partial response among 32 patients
      who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who
      achieved best response of PR or SD were superior in TTP and OS than patients with
      disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P <
      0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or
      2nd line chemotherapy were superior in TTP than patients who received over 2nd
      line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005). CONCLUSIONS: The
      incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based
      systemic therapy should be recommended to improve the prognosis for these
      patients.

PMID- 24447486
TI  - [A novel technique for scintigraphic visualization of internal mammary sentinel
      lymph nodes in breast cancer patients].
AB  - OBJECTIVE: To explore the effects of different injection techniques of
      radiotracer on the visualization rate of internal mammary sentinel lymph nodes
      (IMSLN) in breast cancer patients. METHODS: A series of 137 consecutive breast
      cancer patients was included in this prospective study. Fifty-eight patients
      (group A) received the radiotracer (99)Tc(m)-sulphur colloid injected only into 1
      2 points in the breast parenchyma in one quadrant, and seventy-nine patients
      (group B) received the radiotracer injection into the breast parenchyma in two
      quadrants of the breast. The differences of IMSLN visualization rates of the two
      groups were compared and the relevant affecting factors were analyzed. RESULTS:
      The IMSLN visualization rate of the group B (70.9%, 56/79) was significantly
      higher than that of the group A (13.8%, 8/58) (P < 0.001). Both techniques seemed
      to be reliable to identify sentinel lymph node in the axilla (98.7% vs. 98.3%, P
      = 0.825). In addition, the visualization rate of internal mammary hotspots
      (82.2%) was more commonly seen in patients receiving injection of a larger volume
      of radiotracer ( >= 0.5 ml/point) than those receiving a smaller volume of
      radiotracer (<0.5 ml/point, 55.9%, P = 0.011). CONCLUSIONS: The modified
      injection technique (two quadrants, large volume radiotraver, and ultrasound
      guidance) can significantly improve the visualization rate of IMSLN. Our findings
      should make the biopsy of IMSLN widely implemented and provide an effective and
      minimally invasive technique to evaluate the internal mammary lymph node status.

PMID- 24447487
TI  - [Long-term outcome and analysis of prognostic factors in 114 cases of
      postoperative stage III gastric cancer].
AB  - OBJECTIVE: To analyze the results of long-term follow up of patients with
      postoperative stage III gastric cancer and the prognostic factors. METHODS: We
      retrospectively analyzed the clinicopathological data of 114 patients with stage
      III gastric cancer treated in our hospital from April 1998 to January 2006.
      Kaplan-Meier univariate analysis and Cox regression analysis were performed to
      evaluate the candidate prognostic factors, such as gender, age, pathological
      stage, histological differentiation, lymphovascular tumor thrombus, tumor
      residual and postoperative chemotherapy. RESULTS: In the 114 cases, the 5-year
      overall survival rate was 28.6% and 10-year survival rate was 22.6%. The 5-year
      survival rates of stage IIIA, IIIB and IIIC patients were 38.3%, 33.8% and 19.5%,
      respectively, and 10-year survival rates were 33.5%, 29.6% and 11.1%,
      respectively. Univariate analysis showed that pathological stage, tumor residual
      and postoperative chemotherapy were significantly correlated with prognosis (P <
      0.05). Multivariate analysis showed that pathological stage, tumor residual and
      postoperative chemotherapy were independent prognostic factors of stage III
      gastric cancer patients (P < 0.05 for all). CONCLUSIONS: The long-term survival
      of stage III gastric cancer patients remains poor. Pathological stage, tumor
      residual and postoperative chemotherapy are the most significant factors
      influencing prognosis of stage III gastric cancer after radical resection.
      Postoperative chemotherapy can improve their survival.

PMID- 24447488
TI  - [Clinical features and prognostic factors in patients with leptomeningeal
      metastases].
AB  - OBJECTIVE: To investigate the clinical characteristics and prognostic factors of
      leptomeningeal metastases (LM) from solid tumors and to develop better treatment
      strategies. METHODS: The clinical characteristics and follow-up results of 77
      cases of leptomeningeal metastases (LM) from solid tumors diagnosed and treated
      in our hospital from 2002 to 2011 were retrospectively analyzed. Clinical
      characteristics, treatment methods and overall survival were analyzed using
      Kaplan-Meier method and Cox regression model. RESULTS: The median survival time
      for all the patients was 88 days. KPS score, control of the primary tumor and
      systemic treatment were correlated with survival time for the patients (P < 0.05
      for all). The median survival time of systemic treatment was 150 d and those
      without systemic treatment (chemotherapy and/or targeted therapy) after LM was 60
      d (P = 0.001). Systemic therapy combined with local treatment (radiotherapy to
      the meninges or intrathecal chemotherapy) further improved the survival time of
      patients. Multivariate analysis showed that KPS and short-term therapeutic
      response for the LM were independent prognostic factors (P < 0.05 for both).
      CONCLUSIONS: KPS and short-term therapeutic response are independent prognostic
      factores for leptomeningeal metastases from solid tumors. Systemic chemotherapy
      or targeted therapy can prolong the survival time. Systemic treatment
      (chemotherapy and/or targeted therapy) combined with radiation therapy or
      intrathecal injection may further improve the clinical outcomes.

PMID- 24447489
TI  - [Clinical analysis of 27 cases of well differentiated carcinoma of the thyroid
      isthmus].
AB  - OBJECTIVE: Well differentiated thyroid carcinoma (WDTC) may be located in the
      isthmus. The guidelines now have not mentioned an appropriate procedure for WDTC
      in the isthmus. The aim of this study was to retrospectively analyze the outcomes
      in patients with WDTC in the isthmus treated at our institution. METHODS: Twenty
      seven patients with WDTC in the isthmus were managed by surgery in the Cancer
      Hospital of Chinese Academy of Medical Sciences from 1985-2006. Their demographic
      data, surgical procedures, pathological features, stages and outcomes were
      analyzed. RESULTS: Five patients were men and 22 were women. The median age was
      41 (range, 20-69) years. Nine patients received isthmusectomy, fourteen patients
      received extended isthmusectomy and four received isthmusectomy with unilateral
      lobectomy. There were no complications of recurrent laryngeal nerve palsy or
      hypocalcaemia. The median size of lesion was 1.0 cm(range, 0.5-4.0 cm). Sixteen
      patients had a pathologically T1a lesion (pT1a), seven patients were pT1b, two
      patients were pT2 and two pT3. Three patients had papillary carcinoma detected in
      perithyroid lymph nodes (pN1a). Among the 27 cases, 25 patients had a solitary
      malignant nodule confined to the isthmus, one had two malignant nodules confined
      to the isthmus and one had two malignant nodules located separately in the
      isthmus and right lobe. The patients were followed up with a median follow-up
      time of 85 months(range, 37-274 months). The 5-year recurrence-free survival was
      95.2% and overall survival rate was 100%. CONCLUSIONS: Our results suggest that
      isthmusectomy or extended isthmusectomy are feasible and efficient for the
      patients with WDTC located in the isthmus, and concurrent pretracheal lymph node
      dissection should be considered.

PMID- 24447490
TI  - [Expert group consensus: prevention, diagnosis and treatment of bone loss and
      osteoporosis in postmenopausal breast cancer patients after aromatase inhibitor
      therapy].

PMID- 24447491
TI  - Does a facultative precocious life cycle predispose the marine trematode
      Proctoeces cf. lintoni to inbreeding and genetic differentiation among host
      species?
AB  - Intraspecific variability in parasite life cycle complexity (number of hosts and
      species of hosts in the life cycle) may have an impact how parasite genetic
      variation is partitioned among individual parasites, host individuals or host
      species within a given area. Among digenean trematodes, a three-host life cycle
      is common. However, a few species are precocious and may reach sexual maturity in
      what is typically regarded as the second intermediate host. The objective of this
      study was to determine whether a precocious life cycle predisposes digeneans to
      possible inbreeding or genetic subdivision among host species. As a study system,
      we used the digenean Proctoeces cf. lintoni whose metacercariae precociously
      mature (facultative) without a cyst wall in the gonads of multiple sympatric
      species of keyhole limpets (Fissurella spp.), typically regarded as the second
      intermediate hosts. Genotyped parasites were collected from four species of
      limpets and the clingfish Sicyases sanguineus, the third and final host where
      sexual maturity occurs. We found very high microsatellite diversity, Hardy
      Weinberg equilibrium over all genotyped individuals, and little to no genetic
      structuring among parasites collected from the different host species. The fact
      that metacercariae do not encyst in the keyhole limpets, coupled with the high
      mixing potential of an aquatic environment, likely promote panmixia in local
      populations of P. cf. lintoni. 

PMID- 24447492
TI  - Fasting time and lipid parameters: association with hepatic steatosis--data from
      a random population sample.
AB  - BACKGROUND: Current guidelines recommend measuring plasma lipids in fasting
      patients. Recent studies, however, suggest that variation in plasma lipid
      concentrations secondary to fasting time may be minimal. Objective of the present
      study was to investigate the impact of fasting time on plasma lipid
      concentrations (total cholesterol, HDL and LDL cholesterol, triglycerides). A
      second objective was to determine the effect of non-alcoholic fatty liver disease
      exerted on the above-mentioned lipid levels. METHOD: Subjects participating in a
      population-based cross-sectional study (2,445 subjects; 51.7% females) were
      questioned at time of phlebotomy regarding duration of pre-phlebotomy fasting.
      Total cholesterol, LDL and HDL cholesterol, and triglycerides were determined and
      correlated with length of fasting. An upper abdominal ultrasonographic
      examination was performed and body-mass index (BMI) and waist-to-hip ratio (WHR)
      were calculated. Subjects were divided into three groups based on their reported
      fasting periods of 1-4 h, 4-8 h and > 8 h. After application of the exclusion
      criteria, a total of 1,195 subjects (52.4% females) were included in the study
      collective. The Kruskal-Wallis test was used for continuous variables and the chi
      square test for categorical variables. The effects of age, BMI, WHR, alcohol
      consumption, fasting time and hepatic steatosis on the respective lipid variables
      were analyzed using multivariate logistic regression. RESULTS: At multivariate
      analysis, fasting time was associated with elevated triglycerides (p = 0.0047 for
      1-4 h and p = 0.0147 for 4-8 h among females; p < 0.0001 for 1-4 h and p = 0.0002
      for 4-8 h among males) and reduced LDL cholesterol levels (p = 0.0003 for 1-4 h
      and p = 0.0327 for 4-8 h among males). Among males, hepatic steatosis represents
      an independent factor affecting elevated total cholesterol (p = 0.0278) and
      triglyceride concentrations (p = 0.0002). CONCLUSION: Total and HDL cholesterol
      concentrations are subject to slight variations in relation to the duration of
      the pre-phlebotomy fasting period. LDL cholesterol and triglycerides exhibit
      highly significant variability; the greatest impact is seen with the
      triglycerides. Fasting time represents an independent factor for reduced LDL
      cholesterol and elevated triglyceride concentrations. There is a close
      association between elevated lipids and hepatic steatosis.

PMID- 24447494
TI  - Using a color-coded ambigraphic nucleic acid notation to visualize conserved
      palindromic motifs within and across genomes.
AB  - BACKGROUND: Ambiscript is a graphically-designed nucleic acid notation that uses
      symbol symmetries to support sequence complementation, highlight biologically
      relevant palindromes, and facilitate the analysis of consensus sequences.
      Although the original Ambiscript notation was designed to easily represent
      consensus sequences for multiple sequence alignments, the notation's black-on
      white ambiguity characters are unable to reflect the statistical distribution of
      nucleotides found at each position. We now propose a color-augmented ambigraphic
      notation to encode the frequency of positional polymorphisms in these consensus
      sequences. RESULTS: We have implemented this color-coding approach by creating an
      Adobe Flash(r) application ( http://www.ambiscript.org) that shades and colors
      modified Ambiscript characters according to the prevalence of the encoded
      nucleotide at each position in the alignment. The resulting graphic helps viewers
      perceive biologically-relevant patterns in multiple sequence alignments by
      uniquely combining color, shading, and character symmetries to highlight
      palindromes and inverted repeats in conserved DNA motifs. CONCLUSION: Juxtaposing
      an intuitive color scheme over the deliberate character symmetries of an
      ambigraphic nucleic acid notation yields a highly-functional nucleic acid
      notation that maximizes information content and successfully embodies key
      principles of graphic excellence put forth by the statistician and graphic design
      theorist, Edward Tufte.

PMID- 24447493
TI  - Plasma free fatty acids and risk of stroke in the Cardiovascular Health Study.
AB  - BACKGROUND: Although free fatty acids have been positively associated with risk
      factors for stroke, the role of plasma free fatty acids in the development of
      stroke has not been elucidated in older adults. AIMS: We sought to examine the
      association between plasma free fatty acids and incident stroke. METHODS:
      Prospective cohort of 4369 men and women>=65 years of age in the Cardiovascular
      Health Study. Plasma levels of free fatty acids were measured at the 1992-1993
      examination and stroke events were adjudicated by a committee of experts
      including neurologists and neuroradiologists. Cox regression was used to estimate
      the relative risk of stroke associated with free fatty acids concentrations.
      RESULTS: The average age among participants was 75+/-5.2 years. During a median
      follow-up of 11.4 years, 732 incident strokes occurred. The crude incidence rates
      of stroke were 14.5, 14.9, and 17.6 per 1000 person-years across increasing
      tertiles of plasma free fatty acids. The adjusted hazard ratio (95% confidence
      interval) for incident stroke was 1.05 (0.97-1.14) per standard deviation
      increase in plasma free fatty acids. Restriction to ischemic stroke did not alter
      the results [hazard ratio (95% confidence interval): 1.04 (0.96-1.14) per
      standard deviation higher free fatty acids], and there was no effect modification
      by adiposity (P interaction=0.18) or by diabetes (P interaction=0.15).
      CONCLUSION: Our data did not show an association of plasma free fatty acids with
      incident stroke among community dwelling older adults.

PMID- 24447495
TI  - Molecular detection of Diphyllobothrium nihonkaiense in humans, China.
AB  - The cause of diphyllobothriosis in 5 persons in Harbin and Shanghai, China,
      during 2008-2011, initially attributed to the tapeworm Diphyllobothrium latum,
      was confirmed as D. nihonkaiense by using molecular analysis of expelled
      proglottids. The use of morphologic characteristics alone to identify this
      organism was inadequate and led to misidentification of the species. 

PMID- 24447496
TI  - Anticoagulation for critically ill cardiac surgery patients: is primary
      bivalirudin the next step?
AB  - OBJECTIVE: Anticoagulation with unfractionated heparin (UFH) in critically ill
      cardiac surgery patients has several limitations, including the risk of heparin
      induced thrombocytopenia. The use of a direct thrombin inhibitor, such as
      bivalirudin, might either treat this complication or completely eliminate it. The
      aim of the present study was to analyze the use of bivalirudin in this setting,
      as either a secondary drug switching from heparin or as the primary
      anticoagulant, and to evaluate clinical outcomes. DESIGN: Propensity-matching
      retrospective analysis. SETTING: A cardiac surgery intensive care unit.
      PARTICIPANTS: One hundred propensity-matched patients who received heparin or
      bivalirudin. INTERVENTIONS: Bivalirudin was administered as a first-line or
      second-line drug after heparin discontinuation in case of thrombocytopenia and
      suspicion of heparin-induced thrombocytopenia. Twenty-six patients (52%) received
      bivalirudin as a primary anticoagulant, while 24 patients (48%) received
      bivalirudin after switching from heparin. MEASUREMENTS AND MAIN RESULTS:
      Bivalirudin treatment was associated with a reduction of major bleeding (p=0.05)
      compared with the control group. Interestingly, in an intention-to-treat
      analysis, patients receiving primary bivalirudin showed significant reductions in
      minor bleeding (p=0.04), and mortality (p=0.01) compared with the secondary
      bivalirudin group and, similarly, compared with the rest of the study population
      (UFH and secondary bivalirudin patients, p=0.01 and p=0.05, respectively).
      Predictors of hospital mortality by multivariate analysis included urgent
      admission (odds ratio [OR]=2.7; 95 confidence interval [CI], 1.03-7.2; p=0.04),
      ;septic shock (OR=8.0; 95 CI, 2.26-28.7; p<0.005) and primary therapy with UFH
      (OR=19.2; 95 CI, 2.2-163.9; p=0.007). CONCLUSIONS: Novel anticoagulant strategies
      might play a crucial role in critically ill cardiac surgery patients. In a
      propensity-matched population, results of the present study showed that primary
      bivalirudin anticoagulation may reduce bleeding complications and mortality.

PMID- 24447497
TI  - Incidence and risk factors associated with ipsilateral shoulder pain after
      thoracic surgery.
AB  - OBJECTIVES: This study was designed to determine the incidence and risk factors
      associated with ipsilateral shoulder pain (ISP) after thoracic surgery and to
      investigate characteristics, locations, and severity of ISP. DESIGN: A
      prospective observational study. SETTING: University hospital. PARTICIPANTS: Two
      hundred five patients who underwent thoracic surgery. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Pain at the incisional site and shoulder pain were
      assessed separately using the numeric rating scale (NRS) during the patients'
      stay in the postanesthesia care unit. The overall incidence of ISP was 47.3%. The
      incidence of ISP in thoracotomy patients (58.7%) was substantially higher than in
      video-assisted thoracoscopic surgery patients (20.9%). ISP was described most
      often as a dull aching pain (87%). In approximately half of the patients, ISP was
      located at the posterior side of the shoulder. The severity of ISP was classified
      as moderate to severe in 67% of patients. The potential risk factors associated
      with ISP were surgery using the thoracotomy approach (risk ratio: 2.12, 95%
      confidence interval: 1.16-3.86, p=0.014) and surgical duration>120 minutes (risk
      ratio: 1.61, 95% confidence interval: 1.07-2.44, p=0.023). CONCLUSIONS: The
      incidence of ISP after thoracic surgery was high and the severity of pain was
      significant. The thoracotomy approach and the long duration of surgery are
      potential risk factors for ISP.

PMID- 24447498
TI  - Comparison of two tranexamic acid dose regimens in patients undergoing cardiac
      valve surgery.
AB  - OBJECTIVE: Tranexamic acid (TA), a synthetic antifibrinolytic drug, has been
      shown to reduce postoperative bleeding and the need for allogeneic blood
      transfusion in cardiac surgery. However, the optimal dose regimen of TA is still
      under debate. The aim of this study was to evaluate whether a lower-dose TA
      regimen produced equivalent efficacy to its higher-dose counterpart in reducing
      postoperative bleeding and transfusion needs. DESIGN: A prospective, randomized,
      double-blind trial. SETTING: National Center for Cardiovascular Diseases &
      University Hospital, Beijing, People's Republic of China. PARTICIPANTS: One
      hundred seventy-five patients undergoing cardiac valve surgery were enrolled in
      the study. INTERVENTIONS: All patients were divided randomly into 2 groups. The
      lower-dose TA group received a loading dose of 10 mg/kg, maintenance dose of 2
      mg/kg/h, and a cardiopulmonary bypass pump prime dose of 40 mg; the higher-dose
      TA group received a loading dose of 30 mg/kg, maintenance dose of 16 mg/kg/h, and
      a pump prime dose of 2 mg/kg. MEASUREMENTS AND MAIN RESULTS: The amount of
      postoperative bleeding, the amount and frequency of allogeneic transfusion,
      mortality, and morbidities were recorded. There was no significant difference in
      the volume of 24-hour postoperative bleeding between the lower-dose group and the
      higher-dose group. Other measurements also showed no statistical difference
      between the 2 groups, including the amount and frequency of allogeneic
      transfusion, mortality, and morbidities. CONCLUSION: Lower-dose TA regimen was as
      effective as the higher-dose regimen in reducing postoperative bleeding and
      transfusion needs in patients undergoing cardiac valve surgery.

PMID- 24447499
TI  - United States practice patterns in the use of transesophageal echocardiography
      during adult liver transplantation.
AB  - OBJECTIVE: To characterize contemporary practice patterns in the use of
      transesophageal echocardiography during adult liver transplantation and to
      identify factors preventing more frequent use. DESIGN: Online questionnaire.
      SETTING: Liver transplantation centers in the United States performing 12 or more
      adult liver transplants in 2011. PARTICIPANTS: One representative from each
      qualifying center: The transplant anesthesiology director, a transplant
      anesthesiologist personally known to the authors, or the department of
      anesthesiology chair. INTERVENTIONS: Three e-mail attempts were made to solicit
      participation in the study between June and August 2012. MEASUREMENTS AND MAIN
      RESULTS: Of the 97 institutions identified, an anesthesiologist from each of 79
      (81.4%) centers completed the questionnaire; 38.0% of centers reported routine
      use and 57.0% for special circumstances or rescue situations, yielding an overall
      use rate of 94.9%. This distribution was consistent regardless of operative
      volume, practice size, or academic affiliation. The sole factor predictive of
      routine transesophageal echocardiography use was an overlap between an
      institution's cardiac and transplant anesthesiology teams. In practices not
      routinely employing the technology, the most compelling reason was a sense that
      it was not necessary. Although 69.9% of transplant anesthesiologists reportedly
      were proficient in echocardiography, inadequate anesthesiologist training was
      also a strongly cited hindrance. CONCLUSIONS: Transesophageal echocardiography
      during adult liver transplantation in the United States has become widely
      prevalent, with notable growth in its use as a routine diagnostic and monitoring
      modality. Almost all institutions now use the technology at least occasionally,
      with the participation of cardiac anesthesiologists being predictive of a
      center's routine use.

PMID- 24447500
TI  - Adenosine diphosphate-induced single-platelet count aggregation and bleeding in
      clopidogrel-treated patients undergoing coronary artery bypass grafting.
AB  - OBJECTIVES: To investigate the association between adenosine diphosphate (ADP)
      induced platelet aggregation measured by single-platelet count testing and
      postoperative blood loss in clopidogrel-treated patients with acute coronary
      syndromes undergoing coronary artery bypass grafting (CABG). DESIGN: Prospective
      observational study. SETTING: Clinical study in one cardiac surgery center.
      PARTICIPANTS: Eighty-eight patients treated with clopidogrel (300-600 mg loading
      dose followed by 75 mg daily) within 7 days before CABG. INTERVENTIONS: Platelet
      function was assessed preoperatively by single-platelet count ADP-induced
      platelet aggregation. Postoperative blood loss and transfusion requirements were
      recorded. MEASUREMENTS AND MAIN RESULTS: There was no significant association
      between ADP-induced platelet aggregation and blood loss 12 hours postoperatively
      (estimate -7.51; 95% confidence interval [CI]: -16.9-1.9; p = 0.12). ADP-induced
      platelet aggregation was associated significantly with the number of platelet
      concentrates administered within 24 hours after surgery (incidence rate ratio
      [IRR] 0.95; 95% CI: 0.92-0.98; p<0.01), but not to the number of packed red blood
      cells (IRR 0.98; 95% CI: 0.95-1.01; p = 0.14). CONCLUSIONS: Preoperative ADP
      induced platelet aggregation measured by single-platelet count testing in
      clopidogrel-treated patients with acute coronary syndromes undergoing CABG was
      not associated with postoperative blood loss or packed red blood cells
      transfused, but was associated significantly with number of platelet concentrates
      administered during the initial 24 postoperative hours.

PMID- 24447501
TI  - Levosimendan improves renal outcome in cardiac surgery: a randomized trial.
AB  - OBJECTIVE: The effect of levosimendan on renal function in patients with low
      ejection fraction undergoing mitral valve surgery was investigated. DESIGN: A
      prospective, double-blinded, randomized clinical trial. SETTING: Tertiary
      teaching and research hospital. PARTICIPANTS: Of a total of 147 patients, 128
      patients completed the study. In the levosimendan group (n = 64), levosimendan
      was administered in addition to standard inotropic support; whereas, in the
      control group (n = 64), only standard inotropic support was given. INTERVENTIONS:
      In the levosimendan group, a loading dose of levosimendan (6 MUg/kg) was
      administered after removal of the aortic cross-clamp, followed by an infusion
      (0.1 MUg/kg/min) in addition to standard inotropic therapy for 24 hours. In the
      control group, only standard inotropic therapy was administered. Preoperative
      characteristics, serum creatinine (sCr) levels, and estimated glomerular
      filtration rate (eGFR) were determined preoperatively, on postoperative days 1,
      3, and 10. Independent risk factors for renal replacement therapy (RRT)
      requirement were investigated with stepwise multivariate logistic regression
      analysis. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the effect of
      levosimendan on postoperative renal clearance (sCr and eGFR). The secondary
      endpoint was the effect of levosimendan on clinical outcomes (length of intensive
      care unit and hospital stays, need for RRT). Preoperative characteristics and
      eGFR were similar between the groups (p>0.05). On postoperative days 1 and 3, sCr
      values were lower and eGFR values were higher in the levosimendan group in
      comparison with the control group (p = 0.0001, p = 0.009, respectively). Six
      patients (9.4%) in the levosimendan group and 10 patients (15.6%) in the control
      group required RRT therapy (p = 0.284). Independent risk factors for need of RRT
      include preoperative sCr value between 1.2 to 2.09 mg/dL and>=2.1 mg/dL (p<
      0.05). CONCLUSIONS: Perioperative treatment with levosimendan in addition to
      standard inotropic therapy in patients with a low ejection fraction undergoing
      mitral valve surgery improved immediate postoperative renal function and reduced
      need for RRT.

PMID- 24447502
TI  - Relationship between tricuspid annular excursion and velocity in cardiac surgical
      patients.
AB  - OBJECTIVES: The primary objective of this study was to establish the relationship
      among tricuspid annular velocity (S'), tricuspid annular plane systolic excursion
      (TAPSE), and stroke volume (SV) in a cardiac surgical population with and without
      right ventricular (RV) dysfunction. The secondary objective was to assess the
      effect of ephedrine on these relationships in a population without RV
      dysfunction. DESIGN: Prospective, nonrandomized, unblinded study. SETTING: Single
      tertiary-level, university-affiliated hospital. PARTICIPANTS: Twenty-seven
      patients undergoing elective coronary artery bypass grafting with no evidence of
      RV dysfunction (Group 1). Sixteen ventilated postcardiac surgical patients with
      suspected RV dysfunction (Group 2). INTERVENTIONS: Ten mg of intravenous
      ephedrine to Group 1 only. MEASUREMENTS AND MAIN RESULTS: Using transthoracic
      echocardiography, S' and TAPSE were measured using color tissue Doppler applied
      at the RV base in a 4-chamber view. SV was calculated using thermodilution. Six
      patients in Group 1 and 6 patients in Group 2 were excluded because of poor
      imaging or ineligibility. Modest correlation was found between TAPSE and SV in
      Group 1 (R = 0.50, p<0.001). There was no correlation between TAPSE and SV in
      Group 2. There was no correlation between S' and SV in both groups. In Group 1,
      the relationship between TAPSE and S' was curvilinear (R = 0.74 pre-ephedrine,
      p<0.001; R = 0.64, p = 0.009 post-ephedrine). There was no relationship between
      TAPSE and S' in Group 2. Ephedrine increased S' and TAPSE. The TAPSE-S'
      relationship was not significantly altered. CONCLUSIONS: In the presence of RV
      dysfunction, TAPSE did not correlate with cardiac output. In the absence of RV
      dysfunction, the relationship between TAPSE and S' described a curvilinear
      relationship.

PMID- 24447503
TI  - Right ventricular function during one-lung ventilation: effects of pressure
      controlled and volume-controlled ventilation.
AB  - OBJECTIVES: To test the effects of pressure-controlled (PCV) and volume
      controlled (VCV) ventilation during one-lung ventilation (OLV) for thoracic
      surgery on right ventricular (RV) function. DESIGN: A prospective, randomized,
      double-blind, controlled, crossover study. SETTING: A single university hospital.
      PARTICIPANTS: Fourteen pairs of consecutive patients scheduled for elective
      thoracotomy. INTERVENTIONS: Patients were assigned randomly to ventilate the
      dependent lung with PCV or VCV mode, each in a randomized crossover order using
      tidal volume of 6 mL/kg, I: E ratio 1: 2.5, positive end-expiratory pressure
      (PEEP) of 5 cm H2O and respiratory rate adjusted to maintain normocapnia.
      MEASUREMENTS AND MAIN RESULTS: Intraoperative changes in RV function (systolic
      and early diastolic tricuspid annular velocity (TAV), end-systolic volume (ESV),
      end-diastolic volume (EDV) and fractional area changes (FAC)), airway pressures,
      compliance and oxygenation index were recorded. The use of PCV during OLV
      resulted in faster systolic (10.1+/-2.39 vs. 5.8+/-1.67 cm/s, respectively),
      diastolic TAV (9.2+/-1.99 vs. 4.6+/-1.42 cm/s, respectively) (p<0.001) and
      compliance and lower ESV, EDV and airway pressures (p<0.05) than during the use
      of VCV. Oxygenation indices were similar during the use of VCV and PCV.
      CONCLUSIONS: The use of PCV offers more improved RV function than the use of VCV
      during OLV for open thoracotomy. These results apply specifically to younger
      patients with good ventricular and pulmonary functions.

PMID- 24447504
TI  - Subtyping Cryptosporidium ubiquitum,a zoonotic pathogen emerging in humans.
AB  - Cryptosporidium ubiquitum is an emerging zoonotic pathogen. In the past, it was
      not possible to identify an association between cases of human and animal
      infection. We conducted a genomic survey of the species, developed a subtyping
      tool targeting the 60-kDa glycoprotein (gp60) gene, and identified 6 subtype
      families (XIIa-XIIf) of C. ubiquitum. Host adaptation was apparent at the gp60
      locus; subtype XIIa was found in ruminants worldwide, subtype families XIIb-XIId
      were found in rodents in the United States, and XIIe and XIIf were found in
      rodents in the Slovak Republic. Humans in the United States were infected with
      isolates of subtypes XIIb-XIId, whereas those in other areas were infected
      primarily with subtype XIIa isolates. In addition, subtype families XIIb and XIId
      were detected in drinking source water in the United States. Contact with C.
      ubiquitum-infected sheep and drinking water contaminated by infected wildlife
      could be sources of human infections. 

PMID- 24447506
TI  - Acute kidney injury: taking aim at colistin.

PMID- 24447505
TI  - Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in
      gastric cancer cells.
AB  - RUNX3 is a tumor suppressor for a variety of cancers. RUNX3 suppresses the
      canonical Wnt signaling pathway by binding to the TCF4/beta-catenin complex,
      resulting in the inhibition of binding of the complex to the Wnt target gene
      promoter. Here, we confirmed that RUNX3 suppressed Wnt signaling activity in
      several gastric cancer cell lines; however, we found that RUNX3 increased the Wnt
      signaling activity in KatoIII and SNU668 gastric cancer cells. Notably, RUNX3
      expression increased the ratio of the Wnt signaling-high population in the
      KatoIII cells. although the maximum Wnt activation level of individual cells was
      similar to that in the control. As found previously, RUNX3 also binds to TCF4 and
      beta-catenin in KatoIII cells, suggesting that these molecules form a ternary
      complex. Moreover, the ChIP analyses revealed that TCF4, beta-catenin and RUNX3
      bind the promoter region of the Wnt target genes, Axin2 and c-Myc, and the
      occupancy of TCF4 and beta-catenin in these promoter regions is increased by the
      RUNX3 expression. These results suggest that RUNX3 stabilizes the TCF4/beta
      catenin complex on the Wnt target gene promoter in KatoIII cells, leading to
      activation of Wnt signaling. Although RUNX3 increased the Wnt signaling activity,
      its expression resulted in suppression of tumorigenesis of KatoIII cells,
      indicating that RUNX3 plays a tumor-suppressing role in KatoIII cells through a
      Wnt-independent mechanism. These results indicate that RUNX3 can either suppress
      or activate the Wnt signaling pathway through its binding to the TCF4/beta
      catenin complex by cell context-dependent mechanisms. 

PMID- 24447507
TI  - Spatial mobility and environmental effects on obesity.
AB  - In this paper, we used a randomized experiment, the Moving to Opportunity for
      Fair Housing Demonstration (MTO) study, to assess whether several environmental
      attributes are causes of obesity. To accomplish our objective, we linked the MTO
      data with several external data sources that provide information on potential
      determinants of obesity including food prices, restaurant and food store
      availability, physical activity facility availability, the prevalence of crime
      and population density. We find that the environmental factors we examined are
      unable to explain the observed decrease in obesity associated with the MTO
      experiment among low-income minority women. 

PMID- 24447508
TI  - Antibiotic susceptibility of bacteria isolated from infections in cats and dogs
      throughout Europe (2002-2009).
AB  - A monitoring program of the pre-treatment susceptibility of clinical isolates of
      bacteria from diseased dogs and cats was active between the years 2002 and 2009.
      Susceptibility of each isolated strain to a panel of nine antibiotics
      (amoxicillin/clavulanic acid, ampicillin, penicillin, clindamycin, doxycycline,
      enrofloxacin, marbofloxacin, trimethoprim and trimethoprim/sulfamethoxazole) was
      assessed. The Minimum Inhibitory Concentration (MIC) of marbofloxacin was also
      determined by a standardized microdilution technique following CLSI
      recommendations. In total, 1857 bacterial strains were collected throughout
      Europe from cases of otitis, respiratory, urinary and dermatological infections.
      Although bacterial susceptibility varied for each of the antibiotics within the
      panel, patterns of susceptibility were similar to those described in the
      literature for comparable time periods and geographical areas. With a clinical
      resistance varying from 0 to 14.48% against the isolated strains, marbofloxacin
      susceptibility was very high and remains an effective antibiotic for the
      treatment of otitis, urinary, respiratory and dermatological infections in
      companion animals. 

PMID- 24447509
TI  - Holding a country countdown to 2015 conference on Millennium Development Goals
      (MDGs) - the Zambian experience.
AB  - Initiatives such as the Country Countdown to 2015 Conference on Millennium
      Development Goals (MDGs) have provided countries with high maternal and child
      deaths like Zambia a platform to assess progress, discuss challenges and share
      lessons learnt as a conduit for national commitment to reaching and attaining the
      MDGs four and five. This paper discusses and highlights the process of holding a
      successful country countdown conference and shares Zambia's experience with other
      countries planning to organise country countdown to 2015 Conferences on MDGs. 

PMID- 24447510
TI  - Pain referral and regional deep tissue hyperalgesia in experimental human hip
      pain models.
AB  - Hip disorder patients typically present with extensive pain referral and
      hyperalgesia. To better understand underlying mechanisms, an experimental hip
      pain model was established in which pain referrals and hyperalgesia could be
      studied under standardized conditions. In 16 healthy subjects, pain was induced
      by hypertonic saline injection into the gluteus medius tendon (GMT), adductor
      longus tendon (ALT), or gluteus medius muscle (GMM). Isotonic saline was injected
      contralaterally as control. Pain intensity was assessed on a visual analogue
      scale (VAS), and subjects mapped the pain distribution. Before, during, and after
      injections, passive hip joint pain provocation tests were completed, together
      with quantitative sensory testing as follows: pressure pain thresholds (PPTs),
      cuff algometry pain thresholds (cuff PPTs), cutaneous pin-prick sensitivity, and
      thermal pain thresholds. Hypertonic saline injected into the GMT resulted in
      higher VAS scores than hypertonic injections into the ALT and GMM (P<.05).
      Referred pain areas spread to larger parts of the leg after GMT and GMM
      injections compared with more regionalized pain pattern after ALT injections
      (P<.05). PPTs at the injection site were decreased after hypertonic saline
      injections into GMT and GMM compared with baseline, ALT injections, and isotonic
      saline. Cuff PPTs from the thigh were decreased after hypertonic saline
      injections into the ALT compared with baseline, GMT injections, and isotonic
      saline (P<.05). More subjects had positive joint pain provocation tests after
      hypertonic compared with isotonic saline injections (P<.05), indicating that this
      provocation test also assessed hyperalgesia in extra-articular soft tissues. The
      experimental models may open for better understanding of pain mechanisms
      associated with painful hip disorders. 

PMID- 24447511
TI  - Involvement of RVM-expressed P2X7 receptor in bone cancer pain: mechanism of
      descending facilitation.
AB  - Patients with bone cancer commonly experience bone pain that is severe,
      intolerable, and difficult to manage. The rostral ventromedial medulla (RVM)
      plays an important role in the development of chronic pain via descending
      facilitation of spinal nociception. The compelling evidence shows that glial P2X7
      receptor (P2X7R) is involved in the induction and maintenance of chronic pain
      syndromes. The present study explored the mechanism of glial activation and P2X7R
      expression underlying the induction of bone cancer pain. The results demonstrated
      that microglia and astrocytes in the RVM were markedly activated in bone cancer
      rats, and the expression of P2X7R was significantly upregulated. Injection of
      Brilliant Blue G (BBG), an inhibitor of P2X7R, into the RVM significantly
      alleviated pain behaviors of cancer rats, which was supported by intra-RVM
      injection of RNA interference targeting the P2X7R in the RVM. It is suggested
      that activation of microglia-expressed P2X7R in the RVM contributes to bone
      cancer pain. Given that 5-HT in the RVM is involved in modulating spinal
      nociception, changes in 5-HT and Fos expression were addressed in the spinal
      cord. Inhibition of P2X7R by BBG or small-interference RNA targeting P2X7 in the
      RVM markedly reduced 5-HT level and Fos expression in the spinal cord. The data
      clearly suggest that the activation of microglial P2X7R in the RVM contributes to
      the development of bone cancer pain via upregulation of spinal 5HT levels by the
      descending pain facilitatory system. 

PMID- 24447512
TI  - Emotional modulation of placebo analgesia.

PMID- 24447513
TI  - Osteoprotegerin: a new biomarker for impaired bone metabolism in complex regional
      pain syndrome?
AB  - Osteoprotegerin (OPG) is important for bone remodeling and may contribute to
      complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the
      value of OPG as a biomarker for CRPS and a possible correlation with radiotracer
      uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS
      patients (17 women; mean age 50+/-9.0 years; disease duration: 12 weeks [IQR 8
      24]), 10 controls (6 women; mean age 58+/-9.6 years) and 21 patients after
      uncomplicated fractures (12 women; mean age: 43+/-15 years; time after fracture:
      15 weeks [IQR: 6-22]). The CRPS and control patients also underwent TPBS. OPG in
      CRPS patients was significantly increased by comparison with both control groups
      (P=0.001; Kruskal-Wallis test; CRPS patients: 74.1 pg/mL [IQR: 47.1-100.7];
      controls: 46.7 pg/mL [IQR: 35.5-55.0]; P=0.004; fracture patients: 45.9 pg/mL
      [IQR: 37.5-56.7]; P=0.001). As a diagnostic test for CRPS, OPG had a sensitivity
      of 0.74, specificity of 0.80, positive predictive value of 68% and negative
      predictive value of 84%. Receiver operating characteristic curve analysis showed
      an area under the curve of 0.80 (CI: 0.68-0.91). For the CRPS-affected hand, a
      significant correlation between OPG and TPBS region of interest analysis in phase
      III was detected (carpal bones; r=0.391; P=0.03). The persistent OPG increase in
      CRPS indicates enhanced osteoblastic activity shown by increased radiotracer
      uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology
      is likely. OPG might be useful as a biomarker for CRPS.

PMID- 24447514
TI  - Mirror-image pain is mediated by nerve growth factor produced from tumor necrosis
      factor alpha-activated satellite glia after peripheral nerve injury.
AB  - Mirror-image pain is characterized by mechanical hypersensitivity on the
      uninjured mirror-image side. Recent reports favor central mechanisms, but whether
      peripheral mechanisms are involved remains unclear. We used unilateral spinal
      nerve ligation (SNL) to induce mirror-image pain in rats. On the mirror-image
      (contralateral) side, we found that satellite glia in the dorsal root ganglion
      (DRG) were activated, whereas macrophages/Schwann cells in the DRG and
      astrocytes/oligodendrocytes/microglia in the dorsal spinal cord were not.
      Subsequently, an increase in nerve growth factor (NGF) was detected in the
      contralateral DRG, and NGF immunoreactivity was concentrated in activated
      satellite glia. These phenomena were abolished if fluorocitrate (a glial
      inhibitor) was intrathecally injected before SNL. Electrophysiological recordings
      in cultured small DRG neurons showed that exogenous NGF enhanced nociceptor
      excitability. Intrathecal injection of NGF into naive rats induced long-lasting
      mechanical hypersensitivity, similar to SNL-evoked mirror-image pain. Anti-NGF
      effectively relieved SNL-evoked mirror-image pain. In the contralateral DRG, the
      SNL-evoked tumor necrosis factor alpha (TNF-alpha) increase, which started later
      than in the ipsilateral DRG and cerebrospinal fluid, occurred earlier than
      satellite glial activation and the NGF increase. Intrathecal injection of TNF
      alpha into naive rats not only activated satellite glia to produce extra NGF in
      the DRG but also evoked mechanical hypersensitivity, which could be attenuated by
      anti-NGF injection. These results suggest that after SNL, satellite glia in the
      contralateral DRG are activated by TNF-alpha that diffuses from the injured side
      via cerebrospinal fluid, which then activates satellite glia to produce extra NGF
      to enhance nociceptor excitability, which induces mirror-image pain. 

PMID- 24447515
TI  - A gain-of-function voltage-gated sodium channel 1.8 mutation drives intense
      hyperexcitability of A- and C-fiber neurons.
AB  - Therapeutic use of general sodium channel blockers, such as lidocaine, can
      substantially reduce the enhanced activity in sensory neurons that accompanies
      chronic pain after nerve or tissue injury. However, because these general
      blockers have significant side effects, there is great interest in developing
      inhibitors that specifically target subtypes of sodium channels. Moreover, some
      idiopathic small-fiber neuropathies are driven by gain-of-function mutations in
      specific sodium channel subtypes. In the current study, we focus on one subtype,
      the voltage-gated sodium channel 1.8 (Nav1.8). Nav1.8 is preferentially expressed
      in nociceptors, and gain-of-function mutations in Nav1.8 result in painful
      mechanical hypersensitivity in humans. Here, we used the recently developed gain
      of-function Nav1.8 transgenic mouse strain, Possum, to investigate Nav1.8
      mediated peripheral afferent hyperexcitability. This gain-of-function mutation
      resulted in markedly increased mechanically evoked action potential firing in
      subclasses of Abeta, Adelta, and C fibers. Moreover, mechanical stimuli initiated
      bursts of action potential firing in specific subpopulations that continued for
      minutes after removal of the force and were not susceptible to conduction
      failure. Surprisingly, despite the intense afferent firing, the behavioral
      effects of the Nav1.8 mutation were quite modest, as only frankly noxious stimuli
      elicited enhanced pain behavior. These data demonstrate that a Nav1.8 gain-of
      function point mutation contributes to intense hyperexcitability along the
      afferent axon within distinct sensory neuron subtypes. 

PMID- 24447516
TI  - Ca(v)3.2 calcium channels: the key protagonist in the supraspinal effect of
      paracetamol.
AB  - To exert its analgesic action, paracetamol requires complex metabolism to produce
      a brain-specific lipoamino acid compound, AM404, which targets central transient
      receptor potential vanilloid receptors (TRPV1). Lipoamino acids are also known to
      induce analgesia through T-type calcium-channel inhibition (Ca(v)3.2). In this
      study we show that the antinociceptive effect of paracetamol in mice is lost when
      supraspinal Ca(v)3.2 channels are inhibited. Therefore, we hypothesized a
      relationship between supraspinal Ca(v)3.2 and TRPV1, via AM404, which mediates
      the analgesic effect of paracetamol. AM404 is able to activate TRPV1 and weakly
      inhibits Ca(v)3.2. Interestingly, activation of TRPV1 induces a strong inhibition
      of Ca(v)3.2 current. Supporting this, intracerebroventricular administration of
      AM404 or capsaicin produces antinociception that is lost in Ca(v)3.2(-/-) mice.
      Our study, for the first time, (1) provides a molecular mechanism for the
      supraspinal antinociceptive effect of paracetamol; (2) identifies the
      relationship between TRPV1 and the Ca(v)3.2 channel; and (3) suggests supraspinal
      Ca(v)3.2 inhibition as a potential pharmacological strategy to alleviate pain.

PMID- 24447517
TI  - Renal function evaluation in patients undergoing orthotopic bladder substitution:
      a systematic review of literature.
AB  - Renal function (RFn) after orthotopic bladder substitution (OBS) is a critical
      point to be assessed. We performed a systematic review of MEDLINE for full length
      peer reviewed English articles from the year 2000 till January 2013. We included
      only original articles and excluded reviews, editorials and replies and abstracts
      presented in conferences. The outcome is formulated in research questions; what
      is the status of RFn after OBS? Which is better, the direct free-refluxing or
      anti-refluxing ureteroileal anastomosis (UIA) techniques? Studies reporting RFn
      as secondary outcome were also reported. A total of 129 publications were
      reviewed for full text and only 41 were included in this review. All studies were
      of low level of evidence and grade of recommendations. Only 3 randomized
      controlled trials were included and were of poor quality. Renal function after
      OBS was poorly described in the literature with no universal definition about RFn
      deterioration or outcome with no consensus on the best evaluation method. Urinary
      obstruction, chemotherapy and pyelonephritis appeared significant factors but
      with insufficient evidence. There is a universal trend to use the free refluxing
      technique for UIA to avoid complications of anti-refluxing techniques. However,
      the anti-reflux technique proved acceptable outcome in experienced hands. There
      is marked heterogeneity and underestimation of RFn evaluation among reported
      outcomes after OBS with most publications reporting the incidence of UIA and
      pyelonephritis with paucity reporting absolute figures about RFn measurements. In
      conclusion, urinary tract obstruction remains the main factor of RFn
      deterioration after OBS. Methods evaluating RFn, definitions of RFn outcome and
      factors predicting it are poorly studied in the literature and the current
      evidence is relatively weak to draw solid conclusions. Further well-designed
      studies and consensus about method of assessment and definitions of RFn are
      warranted.

PMID- 24447518
TI  - Apelin inhibits the proliferation and migration of rat PASMCs via the activation
      of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia.
AB  - Apelin is highly expressed in the lungs, especially in the pulmonary vasculature,
      but the functional role of apelin under pathological conditions is still
      undefined. Hypoxic pulmonary hypertension is the most common cause of acute right
      heart failure, which may involve the remodeling of artery and regulation of
      autophagy. In this study, we determined whether treatment with apelin regulated
      the proliferation and migration of rat pulmonary arterial smooth muscle cells
      (SMCs) under hypoxia, and investigated the underlying mechanism and the
      relationship with autophagy. Our data showed that hypoxia activated autophagy
      significantly at 24 hrs. The addition of exogenous apelin decreased the level of
      autophagy and further inhibited pulmonary arterial SMC (PASMC) proliferation via
      activating downstream phosphatidylinositol-3-kinase (PI3K)/protein kinase B
      (Akt)/the mammalian target of Rapamycin (mTOR) signal pathways. The inhibition of
      the apelin receptor (APJ) system by siRNA abolished the inhibitory effect of
      apelin in PASMCs under hypoxia. This study provides the evidence that exogenous
      apelin treatment contributes to inhibit the proliferation and migration of PASMCs
      by regulating the level of autophagy.

PMID- 24447520
TI  - Pathway of nitrous oxide consumption in isolated Pseudomonas stutzeri strains
      under anoxic and oxic conditions.
AB  - The microbial consumption of nitrous oxide (N2O) has gained great interest since
      it was revealed that this process could mitigate the greenhouse effect of N2O.
      The consumption of N2O results from its reduction to dinitrogen gas (N2) as part
      of the denitrification process. However, there is ongoing debate regarding an
      alternative pathway, namely reduction of N2O to NH4(+), or assimilatory N2O
      consumption. To date, this pathway is poorly investigated and lacks unambiguous
      evidence. Enrichment of denitrifying activated sludge using a mineral nitrogen
      free medium rendered a mixed culture capable of anoxic and oxic N2O consumption.
      Dilution plating, isolation and deoxyribonucleic acid fingerprinting identified a
      collection of Pseudomonas stutzeri strains as dominant N2O consumers in both
      anaerobic and aerobic enrichments. A detailed isotope tracing experiment with a
      Pseudomonas stutzeri isolate showed that consumption of N2O via assimilatory
      reduction to NH4(+) was absent. Conversely, respiratory N2O reduction was
      directly coupled to N2 fixation.

PMID- 24447519
TI  - Can a combined screening/treatment programme prevent premature failure of renal
      transplants due to chronic rejection in patients with HLA antibodies: study
      protocol for the multicentre randomised controlled OuTSMART trial.
AB  - BACKGROUND: Renal transplantation is the best treatment for kidney failure, in
      terms of length and quality of life and cost-effectiveness. However, most
      transplants fail after 10 to 12 years, consigning patients back onto dialysis.
      Damage by the immune system accounts for approximately 50% of failing transplants
      and it is possible to identify patients at risk by screening for the presence of
      antibodies against human leukocyte antigens. However, it is not clear how best to
      treat patients with antibodies. This trial will test a combined screening and
      treatment protocol in renal transplant recipients. METHODS/DESIGN: Recipients>1
      year post-transplantation, aged 18 to 70 with an estimated glomerular filtration
      rate>30 mL/min will be randomly allocated to blinded or unblinded screening arms,
      before being screened for the presence of antibodies. In the unblinded arm, test
      results will be revealed. Those with antibodies will have biomarker-led care,
      consisting of a change in their anti-rejection drugs to prednisone, tacrolimus
      and mycophenolate mofetil. In the blinded arm, screening results will be double
      blinded and all recruits will remain on current therapy (standard care). In both
      arms, those without antibodies will be retested every 8 months for 3 years. The
      primary outcome is the 3-year kidney failure rate for the antibody-positive
      recruits, as measured by initiation of long-term dialysis or re-transplantation,
      predicted to be approximately 20% in the standard care group but <10% in
      biomarker-led care. The secondary outcomes include the rate of transplant
      dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of
      adherence with medication and a health economic analysis of the combined
      screening and treatment protocol. Blood samples will be collected and stored
      every 4 months and will form the basis of separately funded studies to identify
      new biomarkers associated with the outcomes. DISCUSSION: We have evidence that
      the biomarker-led care regime will be effective at preventing graft dysfunction
      and expect this to feed through to graft survival. This trial will confirm the
      benefit of routine screening and lead to a greater understanding of how to keep
      kidney transplants working longer. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN46157828.

PMID- 24447521
TI  - Auditory temporal processing deficits and language disorders in patients with
      neurofibromatosis type 1.
AB  - Previous findings from a case report led to the argument of whether other
      patients with neurofibromatosis type 1 (NF1) may have abnormal central auditory
      function, particularly auditory temporal processing. We hypothesized that it is
      associated with language and learning disabilities in this population. The aim of
      this study was to measure central auditory temporal function in NF1 patients and
      correlate it with the results of language evaluation tests. A
      descriptive/comparative study including 25 NF1 individuals and 22 healthy
      controls compared their performances on audiometric evaluation and auditory
      behavioral testing (Sequential Verbal Memory, Sequential Non-Verbal Memory,
      Frequency Pattern, Duration Pattern, and Gaps in Noise Tests). To assess language
      performance, two tests (phonological and syntactic awareness) were also
      conducted. The study showed that all participants had normal peripheral acoustic
      hearing. Differences were found between the NF1 and control groups in the
      temporal auditory processing tests [Sequential Verbal Memory (P=0.009),
      Sequential Non-Verbal Memory (P=0.028), Frequency Patterns (P=0.001), Duration
      Patterns (P=0.000), and Gaps in Noise (P=0.000)] and in language tests. The
      results of Pearson correlation analysis demonstrated the presence of positive
      correlations between the phonological awareness test and Frequency Patterns
      humming (r=0.560, P=0.001), Frequency Patterns labeling (r=0.415, P=0.022) and
      Duration Pattern humming (r=0.569, P=0.001). These results suggest that the
      neurofibromin deficiency found in NF1 patients is associated with auditory
      temporal processing deficits, which may contribute to the cognitive impairment,
      learning disabilities, and attention deficits that are common in this disorder.
      LEARNING OUTCOMES: The reader will be able to: (1) describe the auditory temporal
      processing in patients with neurofibromatosis type 1; and (2) describe the impact
      of the auditory temporal deficits in language in this population.

PMID- 24447522
TI  - Peer educator vs. respiratory therapist support: which form of support better
      maintains health and functional outcomes following pulmonary rehabilitation?
AB  - OBJECTIVE: This study examined if ongoing support delivered by telephone
      following pulmonary rehabilitation (PR) assisted chronic obstructive pulmonary
      disease (COPD) patients to maintain health outcomes. METHODS: Phase one (n=79)
      compared post-rehabilitation telephone-based support delivered by peers compared
      to usual care (UC). The second phase (n=168) compared post-rehabilitation support
      from peer educators, respiratory therapists (RT), or UC. Primary outcome
      variables were St. George's Respiratory Questionnaire (SGRQ) total score and the
      six minute walk test (6MWT). Measures were obtained at baseline, immediately
      following PR, and six-months post PR. RESULTS: Six-month follow-up data for phase
      one was collected for 66 COPD patients (n=35 peer support, n=31 UC) and 142 for
      phase two (n=42 peer support, n=52 RT support, n=48 UC). Per-protocol and
      intention to treat (ITT) analysis in both phases found no significant group by
      time differences for SGRQ or 6MWT. CONCLUSION: Providing peer or RT support via
      telephone following PR was not more effective than UC for maintaining health
      outcomes. PRACTICE IMPLICATIONS: There are concerns with using peers to provide
      ongoing support to COPD patients. Additionally, COPD patients require a higher
      level of care than telephone support can provide.

PMID- 24447523
TI  - Do cancer-specific websites meet patient's information needs?
AB  - OBJECTIVE: To evaluate commonly used cancer websites' information provision, we
      developed and applied an Information Comprehensiveness Tool to breast and
      prostate cancer websites. METHODS: We first collated questions from a systematic
      literature review on patient information needs. We then classified the questions
      in terms of spectrum of care, theme, and nature of question. "Breast cancer" and
      "prostate cancer" were typed into Google, and websites listed on the first page
      of results were selected. Two researchers, blind to each others' scores, assessed
      the same websites using the coding system. Each question was scored on a 3-point
      scale as not (0%), partially (50%) and fully (100%) answered by two researchers.
      Average scores were calculated across all questions. Inter-rater reliability was
      assessed. RESULTS: We identified 79 general, 5 breast, and 5 prostate cancer
      questions. Inter-rater reliability was good, with an intraclass coefficient of
      0.756 (95% CIs 0.729-0.781). 17 questions were not answered thoroughly by any
      website. Questions about "future planning", "monitoring", and "decision-making"
      were discussed least. Biomedical questions scored highest. CONCLUSIONS: More
      comprehensive information needs to be provided on breast and prostate cancer
      websites. PRACTICE IMPLICATIONS: This ICT can improve cancer information online
      and enable patients to engage more actively regarding their information needs.

PMID- 24447524
TI  - A patient representative's journey: working within the NHS as part of a research
      team.

PMID- 24447525
TI  - Injectional anthrax in heroin users, Europe, 2000-2012.

PMID- 24447526
TI  - Visual- spatial capacity: gender and sport differences in young volleyball and
      tennis athletes and non-athletes.
AB  - BACKGROUND: In the general population visual-spatial ability is better in males,
      due to the influence of biological and socio-cultural factors. We know that sport
      activity improves motor skills. The aim of this work is to determine if these
      gender differences exist in young athletes. The orientation test described by
      Terzi and standardized by Cesaroni, used to measure spatial ability, was carried
      out on 60 volleyball or 60 tennis athletes as well as on 60 non-sporting
      subjects. RESULTS: The data analysis revealed a worse performance for non
      athletes in comparison with athletes in both components of test (p < 0.0001; p =
      0.04), with no differences between the volleyball and tennis groups. As far as
      gender comparison is concerned, as expected in the non- sport group the males
      presented better values (p < 0.001; p = 0.006). However in both sports groups
      there weren't any gender differences in either part of the test (p = 0.18; p =
      0.056). CONCLUSIONS: These results confirm that during athletic preparation in
      volleyball and tennis the specific training is able to develop spatial ability.
      Besides, boys and girls have similar performance demands and training experience.
      It appears that this specific training could be responsible for modifying gender
      differences in performance of spatial ability during adolescence.

PMID- 24447527
TI  - CHADS2 score/CHA2 DS2 -VASc score and major artery occlusion in cardioembolic
      stroke patients with nonvalvular atrial fibrillation.
AB  - OBJECTIVE: The associations between the CHADS2 score/CHA2 DS2 -VASc score, and
      the presence of cerebral vessel occlusion on admission were examined in
      cardioembolic stroke patients with nonvalvular atrial fibrillation. METHODS: The
      subjects were 546 consecutive patients hospitalized between April 2007 and
      December 2012 with onset of cardioembolic stroke associated with nonvalvular
      atrial fibrillation within 24 h. The associations between the CHADS2 score/CHA2
      DS2 -VASc score and the presence of occluded cerebral vessels on magnetic
      resonance angiography were evaluated retrospectively. Occluded cerebral vessels
      were classified into the internal carotid artery, middle cerebral artery (M1,
      M2), basilar artery, and other (anterior cerebral artery [A1], posterior cerebral
      artery [P1], vertebral artery). RESULTS: Major artery occlusion was seen in 52%
      of patients with CHADS2 score 0, 52% of patients with score 1, 57% with score 2,
      75% with score 3, and 75% with score >=4. As for the CHA2 DS2 -VASc score, major
      artery occlusion was seen in 62% of patients with score 0, 49% with score 1, 53%
      with score 2, 53% with score 3, 65% with score 4, 71% with score 5, and 82% with
      score >=6. The incidence of concurrent major arterial occlusion increased as both
      scores rose. When classified by occluded blood vessel, the incidence of
      concurrent internal carotid artery occlusion increased as both the CHADS2 and
      CHA2 DS2 -VASc scores increased. CONCLUSION: As the CHADS2 and CHA2 DS2 -VASs
      scores increased, the incidence of concurrent major arterial occlusion,
      particularly internal carotid artery occlusion, increased in patients with
      cardioembolic stroke associated with nonvalvular atrial fibrillation.

PMID- 24447528
TI  - Safety of chronic anticoagulation therapy after endovascular abdominal aneurysm
      repair (EVAR).
AB  - OBJECTIVE: Current data supporting the effect of anticoagulation drug use on
      aneurysm sealing and the durability of endovascular abdominal aneurysm repair
      (EVAR) are conflicting. This study assessed the safety of chronic anticoagulation
      therapy after EVAR. METHODS: Records of 1409 consecutive patients having elective
      EVAR during 1997-2011 who were prospectively followed were reviewed. Survival,
      reintervention, conversion, and endoleak rates were analyzed in patients with and
      without chronic anticoagulants. Cox proportional hazards models were used to
      estimate the effect of anticoagulation therapy on outcomes. RESULTS: One-hundred
      and three (7.3%) patients were on chronic anticoagulation drugs (80 on vitamin K
      antagonists) at the time of EVAR. An additional 46 patients started on
      anticoagulants after repair were identified. Patients on chronic anticoagulation
      therapy at repair (mean age 73.6 years; 91 males) had more frequent cardiac
      disease (74.8% vs. 44.2%; p < 00001), but no other differences in demographic and
      major baseline comorbidities with respect to the others. At baseline, mean
      abdominal aortic aneurysm (AAA) diameter was 56.43 mm vs. 54.65 mm (p = .076) and
      aortic neck length 26.54 mm vs. 25.21 mm (p = .26) in patients with and without
      anticoagulants, respectively. At 5 years, freedom from endoleak rates were 55.5%
      vs. 69.9% (p < .0001), and freedom from reintervention/conversion rates were
      69.4% vs. 82.4% (p < .0001) in patients with (including those with delayed drug
      use) and without chronic anticoagulants, respectively. Controlling for covariates
      with the Cox regression method, at a mean follow-up of 64.3 +/- 45.2 months after
      EVAR, use of anticoagulation drugs was independently associated with an increased
      risk of endoleak (odds ratio, OR 1.6; 95% confidence interval, CI: 1.23-2.07; p <
      .0001) and reintervention or late conversion rates (OR 1.8; 95% CI: 1.31-2.48; p
      < .0001). CONCLUSIONS: The safety of anticoagulation therapy after EVAR is
      debatable. Chronic anticoagulation drug use risks exposure to a poor long-term
      outcome. A critical and balanced decision-making approach should be applied to
      patients with AAA and cardiac disease who may require prolonged anticoagulation
      treatment.

PMID- 24447529
TI  - Diabetes and abdominal aortic aneurysms.
AB  - Epidemiologic evidence suggests that patients with diabetes may have a lower
      incidence of abdominal aortic aneurysm (AAA); however, the link between diabetes
      and AAA development and expansion is unclear. The aim of this review is to
      analyze updated evidence to better understand the impact of diabetes on
      prevalence, incidence, clinical outcome, and expansion rate of AAA. A systematic
      review of literature published in the last 20 years using the PubMed and Cochrane
      databases was undertaken. Studies reporting appropriate data were identified and
      a meta-analysis performed using the generic inverse variance method. Sixty-four
      studies were identified. Methodological quality was "fair" in 16 and "good" in 44
      studies according to a formal assessment checklist (Newcastle-Ottawa). In 17
      large population prevalence studies there was a significant inverse association
      between diabetes and AAA: pooled odds ratio (OR) 0.80; 95% confidence intervals
      (CI) 0.70-0.90 (p = .0009). An inverse association was also confirmed by pooled
      analysis of data from smaller prevalence studies on selected populations (OR
      0.59; 95% CI 0.35-0.99; p = .05), while no significant results were provided by
      case-control studies. A significant lower pooled incidence of new AAA in
      diabetics was found over six prospective studies: OR 0.54; 95% CI 0.31-0.91; p =
      .03. Diabetic patients showed increased operative (30-day/in-hospital) mortality
      after AAA repair: pooled OR 1.26; 95% CI 1.10-1.44; p = .0008. The increased
      operative risk was more evident in studies with 30-day assessment. In the long
      term, diabetics showed lower survival rates at 2-5 years, while there was general
      evidence of lower growth rates of small AAA in patients with diabetes compared to
      non-diabetics. There is currently evidence to support an inverse relationship
      between diabetes and AAA development and enlargement, even though fair
      methodological quality or unclear risk of bias in many available studies
      decreases the strength of the finding. At the same time, operative and long-term
      survival is lower in diabetic patients, suggesting increased cardiovascular
      burden. The higher mortality in diabetics raises the question as to whether AAA
      repair should be individualized in selected diabetic populations at higher AAA
      rupture risk.

PMID- 24447530
TI  - Management of abdominal compartment syndrome and the open abdomen.
AB  - OBJECTIVES: The management of the abdominal compartment syndrome (ACS) and the
      open abdomen (OA) are important to improve survival after major vascular surgery,
      in particular ruptured abdominal aortic aneurysm (RAAA). The aim is to summarize
      contemporary knowledge in this field. METHODS: The consensus definitions of the
      World Society of the Abdominal Compartment Syndrome (WSACS) that were published
      in 2006 and the clinical practice guidelines published in 2007 were updated in
      2013. Structured clinical questions were formulated (modified Delphi method), and
      the evidence base to answer those questions was evaluated using the Grading of
      Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines.
      RESULTS: Most of the previous definitions were kept untouched, or were slightly
      modified. Four new definitions were added, including a definition of OA and of
      lateralization of the abdominal wall, an important clinical problem to approach
      during prolonged OA treatment. A classification system of the OA was added. Seven
      recommendations were formulated, in summary: Trans-bladder intra-abdominal
      pressure (IAP) should be monitored in patients at risk. Protocolized monitoring
      and management are recommended, and decompression laparotomy if ACS. When OA,
      protocolized efforts to obtain an early abdominal fascial closure, and strategies
      utilizing negative pressure wound therapy should be used, versus not. In most
      cases the evidence was graded as weak or very weak. In six of the structured
      clinical questions, no recommendation could be made. CONCLUSION: This review
      summarizes changes in definitions and management guidelines of relevance to
      vascular surgery, and data on the incidence of ACS after open and endovascular
      aortic surgery.

PMID- 24447531
TI  - MafFilter: a highly flexible and extensible multiple genome alignment files
      processor.
AB  - BACKGROUND: Sequence alignments are the starting point for most evolutionary and
      comparative analyses. Full genome sequences can be compared to study patterns of
      within and between species variation. Genome sequence alignments are complex
      structures containing information such as coordinates, quality scores and synteny
      structure, which are stored in Multiple Alignment Format (MAF) files. Processing
      these alignments therefore involves parsing and manipulating typically large MAF
      files in an efficient way. RESULTS: MafFilter is a command-line driven program
      written in C++ that enables the processing of genome alignments stored in the
      Multiple Alignment Format in an efficient and extensible manner. It provides an
      extensive set of tools which can be parametrized and combined by the user via
      option files. We demonstrate the software's functionality and performance on
      several biological examples covering Primate genomics and fungal population
      genomics. Example analyses involve window-based alignment filtering, feature
      extractions and various statistics, phylogenetics and population genomics
      calculations. CONCLUSIONS: MafFilter is a highly efficient and flexible tool to
      analyse multiple genome alignments. By allowing the user to combine a large set
      of available methods, as well as designing his/her own, it enables the design of
      custom data filtering and analysis pipelines for genomic studies. MafFilter is an
      open source software available at http://bioweb.me/maffilter.

PMID- 24447532
TI  - A cross-sectional study of the environment, physical activity, and screen time
      among young children and their parents.
AB  - BACKGROUND: To develop evidence-based interventions promoting healthy active
      lifestyles among young children and their parents, a greater understanding is
      needed of the correlates of physical activity and screen time in these dyads.
      Physical environment features within neighborhoods may have important influences
      on both children and their parents. The purpose of this study was to examine the
      associations between several features of the physical environment with physical
      activity and screen time among 511 young children (<=5 years old) and their
      parents, after adjusting for socio-demographic factors. METHODS: From May to
      September, 2011, parents of 0-5 year old children from Kingston, Canada completed
      a questionnaire that assessed socio-demographic characteristics, their physical
      activity and screen time, and their child's physical activity and screen time.
      Guided by a previously developed conceptual framework, several physical
      environment features were assessed using Geographic Information Systems
      including, function (walkability), safety (road speed), aesthetics (streetscape),
      and destination (outdoor play/activity space, recreation facilities, distance to
      closest park, yard at home). Multilevel linear regression analyses were used to
      examine the relationships while adjusting for several socio-demographic factors.
      RESULTS: The only independent association observed for the physical environment
      features was between higher outdoor play/activity space and higher screen time
      levels among parents. Several associations were observed with socio-demographic
      variables. For physical activity, child age, child care status, and family
      socioeconomic status (SES) were independent correlates for children while sex was
      an independent correlate for parents. For screen time, child age and family SES
      were independent correlates for children while neighborhood SES was an
      independent correlate for parents. CONCLUSIONS: The findings suggest that socio
      demographic factors, including social environment factors, may be more important
      targets than features of the physical environment for future interventions aiming
      to promote healthy active lifestyles in young children and their parents. Given
      this was one of the first studies to examine these associations in young child
      parent dyads, future research should confirm and build on these findings.

PMID- 24447534
TI  - Pharmacokinetics of a novel orodispersible tablet of sildenafil in healthy
      subjects.
AB  - BACKGROUND: Sildenafil citrate is indicated for the treatment of erectile
      dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate has been
      developed for the benefit of patients who have difficulty swallowing solid dosage
      forms. OBJECTIVE: The main goal of this study was to evaluate the bioequivalence
      of sildenafil ODT with and without water versus marketed sildenafil oral film
      coated tablets. A secondary objective was to evaluate the effects of a high-fat
      meal on the pharmacokinetics of sildenafil ODT. METHODS: The bioequivalence study
      of sildenafil ODT given with and without water versus marketed sildenafil citrate
      film-coated oral tablets was conducted in 36 subjects. In a food-effect study,
      the effect of a standard high-fat meal on the pharmacokinetics of sildenafil ODT
      was evaluated in 12 subjects. Both studies were randomized, open-label,
      crossover, single-dose (50 mg) studies in healthy men aged >=45 years. Plasma
      samples were collected for 14 hours postdose, and pharmacokinetics were
      determined by using noncompartmental analyses. RESULTS: All subjects in both
      studies were Asian males between the ages of 45 and 69 years. Sildenafil ODT
      without water was bioequivalent to the marketed sildenafil film-coated oral
      tablet as the 90% CI for the ratio of geometric means of Cmax, AUC0-infinity, and
      AUC0-last were contained within equivalence limits (80%-125%). When sildenafil
      ODTs were given with water, the 90% CIs for sildenafil AUC0-infinity and AUC0
      last were contained within the range of 80% to 125%; however, the 90% CI for
      sildenafil Cmax was not (79.76-92.78). This difference in Cmax is unlikely to
      have any clinically meaningful impact. High-fat meals reduced the rate but not
      the extent of absorption of sildenafil. Mean Cmax was reduced by 59%, and median
      Tmax was delayed from 0.625 hour (fasting) to 4 hours (high-fat meal). However,
      AUC values were comparable between fed and fasted treatments. CONCLUSIONS:
      Sildenafil ODT, given with or without water, provides equivalent systemic
      exposure compared with marketed sildenafil film-coated oral tablets, thus
      offering a convenient alternative method of administration. Considering the
      results of the food-effect study, sildenafil ODT should be taken on an empty
      stomach. ClinicalTrials.gov identifiers: NCT01254383 (bioequivalence) and
      NCT01254396 (food effect).

PMID- 24447533
TI  - Development of a contemporary globally diverse HIV viral panel by the EQAPOL
      program.
AB  - The significant diversity among HIV-1 variants poses serious challenges for
      vaccine development and for developing sensitive assays for screening,
      surveillance, diagnosis, and clinical management. Recognizing a need to develop a
      panel of HIV representing the current genetic and geographic diversity NIH/NIAID
      contracted the External Quality Assurance Program Oversight Laboratory (EQAPOL)
      to isolate, characterize and establish panels of HIV-1 strains representing
      global diverse subtypes and circulating recombinant forms (CRFs), and to make
      them available to the research community. HIV-positive plasma specimens and
      previously established isolates were collected through a variety of
      collaborations with a preference for samples from acutely/recently infected
      persons. Source specimens were cultured to high-titer/high-volume using well
      characterized cryopreserved PBMCs from National y donors. Panel samples were
      stored as neat culture supernatant or diluted into defibrinated plasma.
      Characterization for the final expanded virus stocks included viral load, p24
      antigen, infectivity (TCID), sterility, coreceptor usage, and near full-length
      genome sequencing. Viruses are made available to approved, interested
      laboratories using an online ordering application. The current EQAPOL Viral
      Diversity panel includes 100 viral specimens representing 6 subtypes (A, B, C, D,
      F, and G), 2 sub-subtypes (F1 and F2), 7 CRFs (01, 02, 04, 14, 22, 24, and 47),
      19 URFs and 3 group O viruses from 22 countries. The EQAPOL Viral Diversity panel
      is an invaluable collection of well-characterized reagents that are available to
      the scientific community, including researchers, epidemiologists, and commercial
      manufacturers of diagnostics and pharmaceuticals to support HIV research, as well
      as diagnostic and vaccine development. 

PMID- 24447535
TI  - The therapeutic target of estrogen receptor-alpha36 in estrogen-dependent tumors.
AB  - Estrogen receptor-alpha36 (ER-alpha36) is a new isoform of estrogen receptors
      without transcriptional activation domains of the classical ER-alpha(ER -
      alpha66). ER-alpha36 is mainly located in cytoplasm and plasma membrane. ER
      alpha36 mediates non-genomic signaling and is involved in genomic signaling of
      other ERs. Recently ER-alpha36 is found to play a critical role in the
      development of estrogen-dependent cancers and endocrine resistance of breast
      cancer. The present article overviews and updates the biological nature and
      function of ER-alpha36, potential interaction of ER-alpha36 with other estrogen
      receptors and growth factor receptors, intracellular signaling pathways,
      potential mechanism by which ER-alpha36 may play an important role in the
      development of tumor resistance to endocrine therapies. 

PMID- 24447536
TI  - Minimally invasive treatment of Peyronie's disease: evidence-based progress.
AB  - Peyronie's disease (PD) is often physically and psychologically devastating for
      patients, and the goal of treatment is to improve symptoms and sexual function
      without adding treatment-related morbidity. The potential for treatment-related
      morbidity after more invasive interventions, e.g. surgery, creates a need for
      effective minimally invasive treatments. We critically examined the available
      literature using levels of evidence to determine the reported support for each
      treatment. Most available minimally invasive treatments lack critical support for
      effectiveness due to the absence of randomised, placebo-controlled trials (RCTs)
      or non-significant results after RCTs. Iontophoresis, oral therapies (vitamin E,
      potassium para-aminobenzoate, tamoxifen, carnitine, and colchicine),
      extracorporeal shockwave therapy, and intralesional injection with verapamil or
      nicardipine have shown mixed or negative results. Treatments that have decreased
      penile curvature deformity in Level 1 or Level 2 evidence-based, placebo
      controlled studies include intralesional injection with interferon alpha-2b or
      collagenase clostridium histolyticum. 

PMID- 24447538
TI  - Automated impedance manometry analysis as a method to assess esophageal function.
AB  - BACKGROUND: Diagnostic evaluation of non-achalasia esophageal dysphagia remains
      challenging because of a lack of a clear relationship between symptoms,
      esophageal contraction patterns, and esophageal bolus flow. This study evaluates
      a novel approach to pressure-impedance analysis called automated impedance
      manometry (AIM) analysis in relation to bolus characteristics, Chicago
      classification metrics, bolus perception, and dysphagia. METHODS: AIM analysis
      was performed on esophageal high resolution manometry-impedance recordings from
      12 healthy controls and 15 patients with dysphagia. In each subject, 10 liquid,
      10 semisolid, and 10 solid swallows were analyzed using AIMplot software. KEY
      RESULTS: This study demonstrated that (i) esophageal pressure-flow parameters
      differ with bolus type (liquid, semisolid, and solids), (ii) impedance at peak
      pressure parameter can discriminate normal from dysphagic subjects with high
      accuracy on a cut-off threshold at 2400 Ohms (kappa 0.77, sensitivity 0.83, and
      specificity 0.93), and (iii) nadir impedance and impedance at peak pressure
      highly correlate with perception of esophageal bolus flow (r = -0.65, p = 0.02; r
      = -0.70, p = 0.01 resp). CONCLUSIONS & INFERENCES: This study presents novel
      esophageal pressure-flow variables in control subjects and in a cohort of
      patients with dysphagia. These variables are altered in relation to bolus
      consistency and can discriminate between subjects with and without symptoms of
      dysphagia. For the first time, we present high resolution esophageal pressure
      flow variables that accurately link in with patient perception of esophageal
      bolus hold up.

PMID- 24447537
TI  - PELP1 oncogenic functions involve alternative splicing via PRMT6.
AB  - Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a proto-oncogene
      that functions as coactivator of the estrogen receptor and is an independent
      prognostic predictor of shorter survival of breast cancer patients. The
      dysregulation of PELP1 in breast cancer has been implicated in oncogenesis,
      metastasis, and therapy resistance. Although several aspects of PELP1 have been
      studied, a complete list of PELP1 target genes remains unknown, and the molecular
      mechanisms of PELP1 mediated oncogenesis remain elusive. In this study, we have
      performed a whole genome analysis to profile the PELP1 transcriptome by RNA
      sequencing and identified 318 genes as PELP1 regulated genes. Pathway analysis
      revealed that PELP1 modulates several pathways including the molecular mechanisms
      of cancer, estrogen signaling, and breast cancer progression. Interestingly, RNA
      seq analysis also revealed that PELP1 regulates the expression of several genes
      involved in alternative splicing. Accordingly, the PELP1 regulated genome
      includes several uniquely spliced isoforms. Mechanistic studies show that PELP1
      binds RNA with a preference to poly-C, co-localizes with the splicing factor SC35
      at nuclear speckles, and participates in alternative splicing. Further, PELP1
      interacts with the arginine methyltransferase PRMT6 and modifies PRMT6 functions.
      Inhibition of PRMT6 reduced PELP1-mediated estrogen receptor activation, cellular
      proliferation, and colony formation. PELP1 and PRMT6 are co-recruited to estrogen
      receptor target genes, PELP1 knockdown affects the enrichment of histone H3R2 di
      methylation, and PELP1 and PRMT6 coordinate to regulate the alternative splicing
      of genes involved in cancer. Collectively, our data suggest that PELP1 oncogenic
      functions involve alternative splicing leading to the activation of unique
      pathways that support tumor progression and that the PELP1-PRMT6 axis may be a
      potential target for breast cancer therapy. 

PMID- 24447539
TI  - Identification of patient-derived outcomes after aortic aneurysm repair.
AB  - OBJECTIVE: Relatively few outcomes have been examined in randomized comparisons
      of endovascular and open aortic aneurysm repair, and no patient input was
      obtained in the selection of these outcomes. The aim of this study was to
      identify patient-derived, potentially novel outcomes that may be used to guide
      future clinical trials in aneurysm surgery. METHODS: Focus group interviews were
      conducted with patients who had undergone endovascular or open aortic aneurysm
      repair. The discussions were transcribed and the transcript was analyzed by two
      indexers using constant-comparison analysis and grounded theory to identify
      potentially novel, patient-derived outcomes. Other potential themes relating to
      the patients' experience and their decision-making were also sought. RESULTS: Six
      focus groups were conducted (three with endovascular aneurysm repair patients and
      three with open aortic aneurysm repair patients), with a median of six
      participants, 2 to 12 months from surgery. Functional outcomes were most commonly
      mentioned and emphasized by patients. Recovery time and energy level were most
      frequently verbalized as important in the decision-making process between
      endovascular and open aneurysm repair. Other potential outcomes identified as
      important to patients included postoperative pain, time to walking normally, loss
      of appetite, extent and location of incisions, impact on cognition, being able to
      go home after surgery, and impact on caregivers. In addition to these outcomes,
      we identified three themes relating to the patient's experience: undervaluing or
      underappreciating the risk of death during surgery, differing informational needs
      and level of involvement in decision-making, and unrealistic patient expectations
      about the risks of and recovery after the procedure. CONCLUSIONS: Functional
      outcomes emerged as most important during qualitative analysis of patients'
      experiences with aneurysm repair. Perceived differences in recovery time were
      identified as an important consideration for aneurysm patients in deciding
      between open and endovascular repair. More work needs to be done clarifying the
      concept of recovery and other related functional outcomes for the development of
      methods to assess and to evaluate these in prospective clinical trials.

PMID- 24447540
TI  - The effect of extremity vascular complications on the outcomes of cardiac support
      device recipients.
AB  - OBJECTIVE: To assess the effect of extremity vascular complications (EVCs,
      including ischemia or vessel trauma) on the outcomes of patients receiving
      cardiac support devices (CSDs, including ventricular assist device [VAD] and
      extracorporeal membrane oxygenation [ECMO]). METHODS: Institutional Review Board
      approved, retrospective review of a prospectively maintained database of all
      temporary and permanent CSD recipients from 7/1/10 to 6/30/12. Patient
      demographics, procedural data, and outcomes were analyzed. The primary endpoint
      was all-cause mortality at 30-days post-CSD initiation. RESULTS: Of 208 patients
      who received CSDs, 31 (14.9%) experienced EVC: 13 (8.9%) of the 146 permanent
      VADs, 10 (26.3%) of the 38 temporary VADs, and 8 (33.3%) of the 24 ECMO patients.
      The 30-day mortality for CSD-EVC patients was not significantly higher than that
      of the CSD patients who did not experience EVC for permanent VAD (15.4% vs 4.5%;
      P = .15) and ECMO patients (50.0% vs 68.75%; P = 1.00), but was significantly
      higher for temporary VAD patients (80.0% vs 35.7%; P = .03). Within the CSD-EVC
      cohort, patients who received a temporary VAD had a significantly higher 30-day
      mortality and decision to withdraw care after EVC compared with those who
      received a permanent VAD (P = .01 and P < .01, respectively). Looking beyond the
      30-day window, EVC was associated with higher mortality rates in the permanent
      VAD population (53.8% vs 25.6%; P = .025) but not the temporary VAD or ECMO
      groups. CONCLUSIONS: In temporary VAD recipients, EVCs result in higher 30-day
      mortality, more frequent withdrawal of care, and shortened survival time relative
      to the global temporary VAD group. EVC in permanent VAD recipients did not affect
      early (30-day) mortality rates, but strongly predicted a higher cumulative
      mortality risk for the 2-year study period. Overall ECMO mortality rates were
      high, and not significantly impacted by the occurrence of EVC. The nature of the
      EVC (cannulation site complication vs embolic injury) did not impact mortality.
      This data provides quality improvement targets for VAD programs.

PMID- 24447541
TI  - Posterior transverse plication of the internal carotid artery to correct for
      kinking.
AB  - BACKGROUND: The occasional need for shortening of the internal carotid artery
      (ICA) following carotid endarterectomy (CEA) to correct for kinking is still
      controversial. Although several technical options have been suggested, the impact
      on perioperative outcome remains unclear, and long-term clinical follow-up is
      lacking. Shortening by resection has a theoretical risk for a twisted anastomosis
      and subsequent ICA thrombosis. Posterior transverse plication (PTP) offers an
      alternative shortening technique without the need for a new anastomosis. We aimed
      to assess the safety and patency of CEA with concomitant PTP. Secondly, we aimed
      to provide an overview of different technical modalities for shortening of the
      carotid artery in current literature. METHODS: Within the time frame of 2000
      through 2011, 29 patients (mean age, 73.4 years) undergoing CEA with additional
      PTP of the ICA and standardized patchplasty were retrospectively identified.
      Patient characteristics, surgical procedural details, and both short- (<30 days)
      and long- (>30 days) term clinical and duplex ultrasound follow-up were
      retrieved. Restenosis was defined as >=50% stenosis on duplex ultrasound. In
      addition, a literature search was performed on different techniques for ICA
      shortening. RESULTS: Thirty-day outcome revealed no deaths or strokes. No
      postprocedural thrombosis or narrowing of the ipsilateral ICA was observed.
      During follow-up (mean, 34.3 months; range, 3-125 months), one patient (4%) died
      of a noncardiovascular cause. Three patients (11%) developed ipsilateral
      neurological symptoms (1 stroke, 2 transient ischemic attacks) after 5, 19, and
      66 months follow-up, respectively. Of these, two patients (7%) had restenosis at
      the site of PTP. Asymptomatic restenosis occurred in one other patient (4%) after
      16 months. CONCLUSIONS: Although the indications for additional shortening
      procedures following CEA need to be defined, in this small series, PTP as an
      additional shortening procedure of the ICA following CEA seems feasible and safe
      with no additional periprocedural risk for narrowing at the plicature or
      thrombosis of the endarterectomy plane. However, restenosis at the plicature may
      hamper the long term benefit of carotid reconstruction.

PMID- 24447542
TI  - Contemporary comparison of supra-aortic trunk surgical reconstructions for
      occlusive disease.
AB  - OBJECTIVE: Open surgical reconstruction for supra-aortic trunk occlusive disease
      persists despite advances in endovascular therapy. Although extrathoracic
      reconstructions developed as a safer alternative to transthoracic
      reconstructions, contemporary national data evaluating relative rates of
      operative outcomes are lacking. METHODS: With use of the National Surgical
      Quality Improvement Program (2005-2011), patients who underwent transthoracic or
      extrathoracic reconstruction were evaluated. Patients with nonocclusive
      indications were excluded. The primary outcome was a composite end point of
      stroke/myocardial infarction (MI)/death. Secondary outcomes were 30-day
      postoperative complications. Univariate and multivariable regression analyses
      were performed. RESULTS: Overall, 83 patients (10.7%) underwent transthoracic
      reconstructions and 692 patients (89.3%) underwent extrathoracic reconstructions.
      Vascular surgeons performed most transthoracic (96%) and extrathoracic (97%)
      reconstructions. The most common extrathoracic reconstructions were carotid
      subclavian bypass (68%), carotid-carotid bypass (14%), and subclavian
      transposition (7%). Less commonly, axillary-axillary bypass (6%), subclavian
      axillary bypass (2%), subclavian-subclavian bypass (1%), and carotid
      transposition (1%) were performed. At the time of operation, 10% (transthoracic
      reconstructions) and 8% (extrathoracic reconstructions) of patients had a
      concurrent carotid endarterectomy (P < .60). Analysis of more than 20
      characteristics showed that the groups did not differ significantly. The two
      groups had similar rates of postoperative stroke (1.2% in the transthoracic
      reconstruction group vs 2.2% in the extrathoracic reconstruction group; P > .99),
      MI (0% vs 1.3%; P = .61), death (2.4% vs 1.3%; P = .33), and stroke/MI/death
      (3.6% vs 3.8%; P > .99). Transthoracic reconstruction patients had longer
      hospital stays (6.3 days vs 4.0 days; P < .0002), received more transfusions
      (8.4% vs 2.5%; P < .0096), and had higher rates of postoperative sepsis (3.6% vs
      0.3%; P < .01) and venous thromboembolic complications (3.6% vs 0.4%; P < .02).
      After adjustment for other factors, including surgical approach, stroke/MI/death
      was significantly associated with postoperative pneumonia (odds ratio [OR], 26.0;
      95% confidence interval [CI], 6.29-108.28; P < .0001), postoperative ventilator
      dependence (OR, 12.45; 95% CI, 2.74-56.48; P = .001), and postoperative return to
      the operating room (OR, 4.75; 95% CI, 1.67-13.54; P = .004). CONCLUSIONS: At U.S.
      hospitals, extrathoracic reconstruction is the more common reconstruction for
      supra-aortic trunk occlusive disease. Both approaches carry acceptably low rates
      of death, MI, and stroke. Transthoracic reconstruction results in more resource
      utilization because of its postoperative complications and greater complexity.

PMID- 24447543
TI  - Risk score for unplanned vascular readmissions.
AB  - OBJECTIVE: Vascular surgery patients have high readmission rates, and
      identification of high-risk groups that may be amenable to targeted interventions
      is an important strategy for readmission prevention. This study aimed to
      determine predictors of unplanned readmission and develop a risk score for
      predicting readmissions after vascular surgery. METHODS: The National Surgical
      Quality Improvement Program database for 2011 was queried for major vascular
      surgical procedures. The primary end point was unplanned 30-day readmissions. The
      data were randomly split into two-thirds for development and one-third for
      validation. Multivariable logistic regression was used to create and validate a
      point score system to predict unplanned readmissions. RESULTS: Overall, 24,929
      patients were included, with 2507 readmissions (10.1%). A point-based scoring
      system was developed with the use of factors predictive for readmission,
      including procedure type; discharge destination; race; non-elective presentation;
      pulmonary, renal, and cardiac comorbidities; diabetes; steroid use;
      hypoalbuminemia; anemia; venothromboembolism before discharge; graft failure
      before discharge; and bleeding disorder. The point score stratified patients into
      3 groups: low risk (0-3 points) with a readmission rate of 5.4%, moderate risk (4
      7 points) with a readmission rate of 8.6%, and high risk (>= 8 points) with a
      readmission rate of 16.4%. The model had a C-statistic = 0.67. CONCLUSIONS:
      Through the use of patient, operative, and predischarge events, this novel
      vascular surgery-specific readmission score accurately identified patients at
      high risk for 30-day unplanned readmission. This model could help direct
      discharge and home health care resources to patients at high risk, ultimately
      reducing readmissions and improving efficiency.

PMID- 24447544
TI  - Contemporary predictors of extended postoperative hospital length of stay after
      carotid endarterectomy.
AB  - INTRODUCTION: Hospital length of stay (LOS) contributes to costs. Carotid
      endarterectomy (CEA) is performed frequently by vascular surgeons, making
      contemporary CEA LOS rates and predictors vital knowledge for quality evaluation
      and cost containment initiatives. METHODS: Using a prospective single-institution
      database, we retrospectively identified consecutive patients undergoing CEA from
      2001 to 2011. Demographic and perioperative factors were prospectively collected.
      The primary end point was extended postoperative LOS (ELOS), defined as
      postoperative LOS >=2 days. Factors associated with ELOS were analyzed in a
      multivariable logistic regression model. Rates of 1-year readmission and death
      were compared with the Kaplan-Meier method (log-rank test). RESULTS: Eight
      hundred forty patients underwent 897 CEAs with 39% of procedures among females
      and 35% for symptomatic disease. One hundred two (11.4%) patients were inpatients
      prior to the day of CEA ("preadmitted"); their preoperative days by definition
      are not included in ELOS. Median postoperative LOS was 1 day (interquartile
      range, 1-2). Four hundred fourteen patients (46.2%) had ELOS. Preadmission was
      associated with ELOS (72% vs 41%; P < .01) and ELOS patients were less likely to
      be discharged home (11.9% vs 1.5%; P < .01). There was no association between
      ELOS and unplanned 30-day postdischarge readmission (6.0% vs 7.0%; P = .59). On
      multivariable analysis, preoperative factors significantly associated with ELOS
      included preadmission (adjusted odds ratio [OR], 3.3; 95% confidence interval
      [CI], 1.9-5.7; P < .001), history of congestive heart failure (OR, 2.1; 95% CI,
      1.1-4.2; P = .03), female gender (OR, 1.9; 95% CI, 1.4-2.6; P < .001), and
      history of chronic obstructive pulmonary disease (OR, 1.7; 95% CI, 1.0-2.9; P =
      .04). Operative factors included electroencephalography change (OR, 1.9; 95% CI,
      1.2-3.2; P = .01), operating room start time after 12:00 pm (OR, 1.7; 95% CI, 1.2
      2.4; P < .01), and total operating room time (OR, 1.5 per hour; 95% CI, 1.2-2.9;
      P < .01). Postoperative factors included transfer to intensive care unit (OR,
      5.4; 95% CI, 3.1-9.4; P < .01), number of in-hospital postoperative complications
      (OR, 3.7; 95% CI, 2.2-6.5; P < .01), and Foley catheter placement (OR, 2.1; 95%
      CI, 1.3-3.4; P < .01). Over 1 year, ELOS was associated with increased hospital
      readmission (93.6% vs 84.7%; log-rank test, P < .01) and decreased survival
      (95.1% vs 98.3%; log-rank test, P < .01). CONCLUSIONS: Nearly half of CEA
      patients were discharged on or after postoperative day 2. Interventions on
      modifiable risk factors, such as early Foley catheter placement to prevent
      urinary retention and morning CEA scheduling, may decrease LOS. ELOS may identify
      a subset of patients at increased risk for long-term readmission and mortality.

PMID- 24447546
TI  - [Papillary lesions of the breast].

PMID- 24447545
TI  - RUNX3 regulates vimentin expression via miR-30a during epithelial-mesenchymal
      transition in gastric cancer cells.
AB  - Runt-related transcription factor 3 (RUNX3) is a putative tumour suppressor via
      regulating the expression of a series of target genes. Clinical studies
      demonstrated that loss of RUNX3 expression is associated with gastric cancer
      progression and poor prognosis, but the underlying mechanism is not entirely
      clear. Accumulating evidence shows that the epithelial-mesenchymal transition
      (EMT) plays an important role in cancer relapse and metastasis. Therefore, we
      addressed whether RUNX3 has a role in the EMT in gastric cancer. Knockdown of
      RUNX3 promoted cell invasion and increased the protein expression of the
      mesenchymal marker vimentin in human gastric cancer cells. Overexpression of
      RUNX3 suppressed cell invasion and decreased the protein expression of vimentin
      in the cells and inhibited gastric cancer cells colonization in nude mice.
      Furthermore, overexpression of RUNX3 increased the expression of microRNA-30a
      (miR-30a), and miR-30a directly targeted the 3' untranslated region of vimentin
      and decreased its protein level. miR-30a inhibitor abrogated RUNX3-mediated
      inhibition of cell invasion and downregulation of vimentin. Thus, RUNX3
      suppressed gastric cancer cell invasion and vimentin expression by activating miR
      30a. In gastric cancer patients, levels of RUNX3 were positively correlated with
      miR-30a and negatively associated with the levels of vimentin. Collectively, our
      data suggest a novel molecular mechanism for the tumour suppressor activity of
      RUNX3. Effective therapy targeting the RUNX3 pathway may help control gastric
      cancer cell invasion and metastasis by inhibiting the EMT. 

PMID- 24447547
TI  - [Diagnostic accuracy and significance of cytopathology in lung cancer].

PMID- 24447548
TI  - [Clinicopathologic features and prognostic factors of malignant phyllodes
      tumors].
AB  - OBJECTIVE: To study the clinicopathologic features of malignant phyllodes tumors
      (PT) by histopathologic analyses, immunohistochemical profiling and DNA content
      assay, and evaluation of the clinical outcome. METHODS: Ten patients with
      malignant PT from 1999 to 2013 who were treated by surgery were enrolled in this
      study. The morphologic characteristics were studied under light microscope,
      standard two-step EnVision method of immunohistochemical staining was used to
      assess the expression of CK5/6, CKpan, 34beta E12, desmin, p63, ER-alpha, PR, Ki
      67, CD34, SMA, p53, p16, bcl-2 and CD117 in the tumors. The corresponding
      paraffin blocks were also used for flow cytometric DNA content assay. These data
      were correlated with the follow-up results. RESULTS: The median age of onset was
      46.5 years old. The mean tumor size was 7.4 cm (2.0-25.0 cm). At the end of the
      follow-up period (22 to 125 months), there were tumor recurrences in 3/8 patients
      and the median time of recurrence was 24 months. Metastasis occurred in 3/8
      patients who all died of the tumors. PT had heterogeneous histology, with stromal
      overgrowth with leaf-like projections, periductal stromal overgrowth, and most
      commonly, diffuse stromal overgrowth with sarcomatous differentiation. The mean
      positive index of Ki-67 was 11.4%. The stromal tumor cells were positive for
      CD34, SMA, p53, p16, and bcl-2 in 3/10, 9/10, 6/10, 8/10, and 4/10 cases,
      respectively. CD117,ER-alpha and PR were negative. Interpretable DNA histograms
      were obtained in nine cases with triploidy in two cases. CONCLUSIONS: The
      diagnosis of malignant PT should be considered based on the diversity of growth
      patterns and heterogeneous histology.Ki-67 and CD34 are valuable diagnostic and
      prognostic factors in patients with malignant PT. Tumors with diffuse stromal
      overgrowth, heterologous elements, Ki-67 >= 20% or aneuploidy are more likely to
      metastasize.

PMID- 24447549
TI  - [Clinicopathologic features of collagenous spherulosis of the breast].
AB  - OBJECTIVE: To investigate the morphological features, immunohistochemical
      phenotype, diagnosis and differential diagnosis of collagenous spherulosis of the
      breast. METHODS: Clinicopathologic observation, immunohistochemistry using
      EnVision method and histochemical staining were applied in 33 cases of
      collagenous spherulosis of the breast. RESULTS: Collagenous spherulosis of the
      breast was a benign lesion, consisting of proliferative myoepithelial and ductal
      epithelial cells. These cells were arranged in a cribriform pattern with
      esinophilic, round, oval or star-shaped fibrillary spherules in the lumen.SMA,
      calponin and p63 by immunohistochemistry identified the proliferative
      myoepithelium, while E-cadherin identified the proliferative ductal epithelial
      cells. The esinophilic spherules were stained with collagen type IV, AB-PAS and
      reticulin. Collagenous spherulosis was often found in sclerosing adenosis.
      CONCLUSIONS: Collagenous spherulosis of the breast is often associated with other
      diseases. It has special morphological presentation and is easily confused with
      malignant tumors such as adenoid cystic carcinoma or cribriform carcinoma in
      situ, and needs to be differentiated from these disease entities.

PMID- 24447550
TI  - [Clinicopathologic features of gastrointestinal stromal tumor with synchronous
      carcinoma].
AB  - OBJECTIVE: To evaluate the clinicopathologic features of gastrointestinal stromal
      tumor (GIST) with synchronous carcinoma and the treatment principle. METHODS:
      Nineteen cases of GIST with synchronous carcinoma were collected from 113 cases
      of GIST from 2002 to 2008. The clinicopathologic features were studied and the
      expression of CD117, CD34, smooth muscle actin and S-100 protein were detected by
      immunohistochemistry using EliVision method. The expression of proliferation
      marker Ki-67 was also studied. GIST with synchronous carcinoma and those without
      carcinoma were compared. RESULTS: Nineteen cases (16.8%) of GIST with synchronous
      carcinoma were found, including 11 males and 8 females (male to female ratio
      1.38: 1.00). The age of the patients ranged from 43 to 66 years (median age 57
      years). Five of 19 cases were located in the inferior segment of esophagus and 14
      were in the gastric wall. The diameter ranged from 0.6 to 3.8 cm [mean (1.91 +/-
      0.92) cm]. Three of 19 cases showed low grade dysplasia, and there was no
      dysplasia in the remaining 16 cases. The number of mitosis ranged from 0 to 4/50
      HPF [mean (0.74 +/- 1.07)/50 HPF]. The Ki-67 proliferative index (number of Ki-67
      positive cell/HPF) ranged from 0 to 7.72% [mean (2.51 +/- 2.20)%]. The
      synchronous carcinomas included two esophageal carcinomas and 17 gastric
      cancers.In contrast, patients of GIST without carcinoma included 52 males and 42
      females (male to female ratio 1.24: 1.00). The age of patients ranged from 43 to
      71 years (median age 55 years). Seventy-nine of the 94 cases were located in the
      stomach, 10 were in the intestine and 5 were in the esophagus. The diameter
      ranged from 2.4 to 15.5 cm [mean (5.42 +/- 6.17) cm].Seventy-nine of the 94 cases
      showed variable degrees of dysplasia, and 12 cases were of high malignant
      potential. The number of mitosis ranged from 0 to 53/50 HPF [average (3.78 +/-
      10.22)/50 HPF]. The Ki-67 proliferative index ranged from 0 to 37.54% [mean (6.78
      +/- 12.45)%]. Comparing these two groups, the male to female ratio of GIST with
      synchronous carcinoma was higher than that of GIST without carcinoma. The average
      diameter of GIST with synchronous carcinoma was smaller than of those without
      carcinoma. The number of mitosis and Ki-67 proliferative index of GIST with
      synchronous carcinoma were significantly lower than those without carcinoma (t' =
      2.809, P < 0.05; t' = 3.095, P < 0.05, respectively). CONCLUSIONS: Sixteen point
      eight percent of GIST may be associated with synchronous carcinoma. There are no
      special clinical symptoms in most of GIST with synchronous carcinoma, as these
      GIST are usually incidental findings. The Ki-67 proliferative index of GIST with
      synchronous carcinoma is significantly lower than that of GIST without
      synchronous carcinoma. Most GIST with synchronous carcinoma can be treated by the
      standard treatment for the accompanying carcinoma, and do not require specific
      additional treatments.

PMID- 24447551
TI  - [Solid variant of angiomatoid fibrous histocytoma:report of 3 cases].
AB  - OBJECTIVE: To study the clinicopathologic features, immunophenotype, molecular
      genetics and differential diagnosis of solid variant of angiomatoid fibrous
      histocytoma. METHODS: The clinicopathologic features of 3 cases of solid variant
      of angiomatoid fibrous histocytoma were analyzed and the literature was reviewed.
      RESULTS: There were a total of 2 males and 1 female. The age of patients ranged
      from 9 to 12 years. The patients presented with a painless mass located in left
      forearm, left knee or back. The lesions were treated by complete surgical
      resection. On gross examination, the tumors varied from 1.6 cm to 4.5 cm in
      greatest dimension. They were well-circumscribed and had pale yellow to grayish
      red solid cut surface. Histologically, the tumor was composed of histocytoid
      cells arranged in sheet-like pattern. A fibrous pseudocapsule surrounded by
      lymphocytes and plasma cells was identified. Immunohistochemical study showed
      that the tumor cells in all cases were positive for vimentin and CD68. They were
      negative for S100 protein, cytokeratin, CD34, CD31, smooth muscle actin, CD35,
      CD21 and CD30. Two cases also expressed CD99 and one of them was positive for
      desmin and epithelial membrane antigen. Fluorescence in-situ hybridization was
      positive for EWSR1 gene. CONCLUSIONS: Solid type represents a variant of
      angiomatoid fibrous histocytoma and is considered as tumor of borderline
      malignant potential. Definitive diagnosis requires thorough histologic
      examination and clinical correlation. Immunohistochemistry and EWSR1 gene study
      are helpful in further delineation and differential diagnosis. Complete resection
      or wide local excision with post-operative follow up is the main modality of
      treatment.

PMID- 24447552
TI  - [Significance of microRNA-16 and bcl-2 expression in T lymphoblastic
      lymphoma/leukemia and its relation with prognosis].
AB  - OBJECTIVE: To study the expression of miR-16 and bcl-2 in T lymphoblastic
      lymphoma/leukemia (T-LBL/ALL) and its relationship to prognosis. METHODS: 70
      cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical
      EnVision method for CD1a, CD3, cCD3, CD7, CD10, CD20, CD23, CD34, CD43, CD45RO,
      CD99, TDT, MPO, bcl-2 and Ki-67. The expression levels of miR-16 were examined by
      TaqMan real-time polymerase chain reaction (RT-PCR). Thirty cases of reactive
      lymph node were selected as control. RESULTS: Among the 70 cases of T-LBL/ALL,
      the percentages of tumor cells expression of TDT, CD99, CD3, CD7, CD10, CD34,
      CD1a, cCD3, bcl-2, CD45RO and CD43 were 94.3% (66/70), 94.3% (66/70), 68.6%
      (48/70), 92.9% (65/70), 32.9% (23/70), 24.3% (17/70), 40.0% (28/70), 51.4%
      (36/70), 34.3% (24/70), 37.1% (26/70), and 48.6% (34/70). Separately, while tumor
      cells expression of MPO, CD20 and CD23 was all negative. A figure of Ki-67
      expression > 80% was found in 24 cases and <= 80% in 46 cases. The expression of
      miR-16 was up-regulated in T-LBL/ALL, and it was 5.07 times of the reactive lymph
      node(P = 0.001). The high expression group of miR-16 was significantly correlated
      with longer over survival (P = 0.041). The prognosis of negative bcl-2 group was
      better than bcl-2 positive one(P = 0.904). The relationship of miR-16 and bcl-2
      was significant(P = 0.042,chi(2) = 4.147). Survival multivariate COX proportional
      hazard regression analysis revealed that the low expression of miR-16 might be a
      independent poor prognosis factor (P = 0.049). CONCLUSIONS: While the high
      expression group of miR-16 has longer OS than that in low expression group. The
      prognosis of bcl-2 negative was better than bcl-2 positive. miR-16 may be a
      independent prognosis factor. The relationship of miR-16 and bcl-2 might
      suggested that gene regulation may be influenced by them.

PMID- 24447553
TI  - [Fibrosarcomatous dermatofibrosarcoma protuberans: a clinicopathological analysis
      of 12 cases].
AB  - OBJECTIVE: To investigate the clinical pathological features of fibrosarcomatous
      dermatofibrosarcoma protuberans (FS-DFSP). METHODS: The clinical history,
      histopathological features and immunohistochemical characteristics were analyzed
      in twelve cases of FS-DFSP from January 1997 to February 2011, and related
      literature were reviewed. RESULTS: Age of the patients (2 females, 10 males) at
      diagnosis ranged from 41 to 70 years (mean 53 years). Among the 12 cases of FS
      DFSP, 9 cases aroused in recurrent ordinary DFSP. Histologically, FS areas in FS
      DFSP were characterized by a fascicular and highly cellular histology, frequently
      showing a characteristic herringbone pattern. FS-DFSP showed diminishment of CD34
      staining in FS areas. The labeling index of Ki-67 was much higher in the FS areas
      (10%-40%) than that in the conventional DFSP areas (2%-5%). All the patients were
      treated by operation with local excision or wide excision. Postoperative
      radiotherapy and chemotherapy was administered in two cases respectively. Follow
      up information in 9 of 12 patients (9 to 86 months) revealed local recurrence in
      6 patients. Distant metastases were seen in two patients. One patient was died in
      the follow up period. CONCLUSIONS: FS-DFSP is a rare and unique subtype of DFSP
      and is associated with significant elevated risk of both local and distance
      metastasis, usually followed by poor outcome. Compared to ordinary DFSP as a
      borderline neoplasm, FS-DFSP should be considered as a malignant tumor.

PMID- 24447554
TI  - [Clinicopathologic features of lymphoepithelioma-like gastric carcinoma and
      literature review].

PMID- 24447555
TI  - [Effect of staining condition on HER2 immunohisto chemistry of breast cancer
      tissues].

PMID- 24447556
TI  - [Application of thioflavin T staining in detection of beta-amyloid].

PMID- 24447557
TI  - [Clinicopathologic characteristics of primary breast leiomyosarcoma: report of a
      case].

PMID- 24447558
TI  - [Secretory breast cancer in a 15-year-old boy: report of a case].

PMID- 24447559
TI  - [Primary cutaneous follicle centre lymphoma: report of a case].

PMID- 24447560
TI  - [Idiopathic arterial calcification of infancy:report of a case].

PMID- 24447561
TI  - [Gastric biopsy diagnosis of non-neoplastic lesions].

PMID- 24447562
TI  - [Pathology of mammary mucinous carcinoma and its molecular markers].

PMID- 24447563
TI  - [Research progress on pathology of osteogenesis imperfecta].

PMID- 24447564
TI  - [Clinicopathologic features of phyllodes tumors and their research progress].

PMID- 24447565
TI  - [Research advance on c-myc in aggressive B cell lymphomas].

PMID- 24447566
TI  - Syndecan-2 regulation of morphology in breast carcinoma cells is dependent on
      RhoGTPases.
AB  - BACKGROUND: While syndecan-2 is usually considered a mesenchymal transmembrane
      proteoglycan, it can be upregulated in some tumour cells, such as the malignant
      breast carcinoma cell line, MDA-MB231. Depletion of this syndecan by siRNA, but
      not other syndecans, has a marked effect on cell morphology, increasing
      spreading, microfilament bundle and focal adhesion formation, with reduced cell
      migration. METHODS: A combination of siRNA transfection, immunofluorescence
      microscopy, phosphoprotein analysis and migration assays was used to determine
      how syndecan-2 may influence the cytoskeleton. RESULTS: The altered adhesion upon
      syndecan-2 depletion was dependent on the RhoGTPases. p190ARhoGAP relocated to
      the margins of spreading cells, where it codistributed with syndecan-4 and active
      beta1-integrin. This was accompanied by increased RhoGAP tyrosine
      phosphorylation, indicative of activity and RhoGTPase suppression. Consistent
      with this, GTP-RhoA was strongly present at the edges of control cells, but lost
      after syndecan-2 reduction by siRNA treatments. Further, RhoA, but not RhoC was
      shown to be essential for the anchored phenotype of these breast carcinoma cells
      that accompanied siRNA-mediated loss of syndecan-2. CONCLUSIONS: Syndecan-2 has a
      key role in promoting the invasive activity of these cells, in part by regulating
      the RhoGTPases. GENERAL SIGNIFICANCE: Syndecan-2, as a cell surface receptor is
      accessible for targeting to determine whether breast tumour progression is
      altered. This article is part of a Special Issue entitled Matrix-mediated cell
      behaviour and properties.

PMID- 24447568
TI  - The energy-conserving electron transfer system used by Desulfovibrio alaskensis
      strain G20 during pyruvate fermentation involves reduction of endogenously formed
      fumarate and cytoplasmic and membrane-bound complexes, Hdr-Flox and Rnf.
AB  - The adaptation capability of Desulfovibrio to natural fluctuations in electron
      acceptor availability was evaluated by studying Desulfovibrio alaskensis strain
      G20 under varying respiratory, fermentative and methanogenic coculture conditions
      in chemostats. Transition from lactate to pyruvate in coculture resulted in a
      dramatic shift in the population structure and closer interspecies cell-to-cell
      interactions. Lower methane production rates in coculture than predicted from
      pyruvate input was attributed to redirection of electron flow to fumarate
      reduction. Without a methanogenic partner, accumulation of H2and formate resulted
      in greater succinate production. Comparative transcript and gene fitness analysis
      in concert with physiological data of G20 wildtype and mutants demonstrated that
      pyruvate fermentation involves respiration of cytoplasmically formed fumarate
      using cytoplasmic and membrane-bound energy-conserving complexes, Rnf, Hdr-Flox-1
      and Hmc. At the low H2/formate levels maintained in coculture, Rnf likely
      functions as proton-pumping ferredoxin (Fd): type-I cytochrome c oxidoreductase,
      which transitions to a proton-pumping Fd(red):  nicotinamide adenine dinucleotide
      (NAD+) oxidoreductase at high H2/formate levels during fermentation in
      monoculture. Hdr-Flox-1 is postulated to recycle Fd(red) via a flavin-based
      electron bifurcation involving NADH, Fdox and the thiol/disulphide-containing
      DsrC. In a menaquinone (MQ)-based electron confurcation reaction, the high
      molecular-weight cytochrome-c3complex, Hmc, is proposed to then couple DsrC(red)
      and periplasmic H2/formate oxidation using the MQ pool to fuel a membrane-bound
      fumarate reductase.

PMID- 24447567
TI  - Matrix regulators in neural stem cell functions.
AB  - BACKGROUND: Neural stem/progenitor cells (NSPCs) reside within a complex and
      dynamic extracellular microenvironment, or niche. This niche regulates
      fundamental aspects of their behavior during normal neural development and
      repair. Precise yet dynamic regulation of NSPC self-renewal, migration, and
      differentiation is critical and must persist over the life of an organism. SCOPE
      OF REVIEW: In this review, we summarize some of the major components of the NSPC
      niche and provide examples of how cues from the extracellular matrix regulate
      NSPC behaviors. We use proteoglycans to illustrate the many diverse roles of the
      niche in providing temporal and spatial regulation of cellular behavior. MAJOR
      CONCLUSIONS: The NSPC niche is comprised of multiple components that include;
      soluble ligands, such as growth factors, morphogens, chemokines, and
      neurotransmitters, the extracellular matrix, and cellular components. As
      illustrated by proteoglycans, a major component of the extracellular matrix, the
      NSPC, niche provides temporal and spatial regulation of NSPC behaviors. GENERAL
      SIGNIFICANCE: The factors that control NSPC behavior are vital to understand as
      we attempt to modulate normal neural development and repair. Furthermore, an
      improved understanding of how these factors regulate cell proliferation,
      migration, and differentiation, crucial for malignancy, may reveal novel anti
      tumor strategies. This article is part of a Special Issue entitled Matrix
      mediated cell behaviour and properties.

PMID- 24447569
TI  - CapR: revealing structural specificities of RNA-binding protein target
      recognition using CLIP-seq data.
AB  - RNA-binding proteins (RBPs) bind to their target RNA molecules by recognizing
      specific RNA sequences and structural contexts. The development of CLIP-seq and
      related protocols has made it possible to exhaustively identify RNA fragments
      that bind to RBPs. However, no efficient bioinformatics method exists to reveal
      the structural specificities of RBP-RNA interactions using these data. We present
      CapR, an efficient algorithm that calculates the probability that each RNA base
      position is located within each secondary structural context. Using CapR, we
      demonstrate that several RBPs bind to their target RNA molecules under specific
      structural contexts. CapR is available at
      https://sites.google.com/site/fukunagatsu/software/capr.

PMID- 24447570
TI  - A non-joint tissue biphasic synovial sarcoma in a dog.
AB  - A subcutaneous tumour was identified in the malar region of a 14-year-old
      neutered female mixed breed dog. The dog was humanely destroyed and necropsy
      examination was performed. The tumour did not invade neighbouring tissues and no
      metastasis was found. Microscopically, the tumour showed a range of features
      including the presence of multinucleated giant cells, chondrocyte differentiation
      and cystic or slit-like structures. All of these features are consistent with
      previously reported descriptions of synovial sarcomas in dogs. Mesenchymal cells
      accounted for the majority of the tumour, but cytokeratin-positive epithelioid
      components were also confirmed by immunohistochemistry. The tumour was diagnosed
      as a biphasic type of synovial sarcoma. Synovial sarcoma in man may develop in
      tissues unrelated to joints and this is the first report of a non-joint synovial
      sarcoma in a dog. 

PMID- 24447571
TI  - Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in
      hair sheep of northeastern Brazil.
AB  - This paper reports a newly described form of skeletal dysplasia affecting
      Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a
      short head and in some cases the animals are smaller and more compact than sheep
      of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that
      die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and
      three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of
      these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were
      humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face
      characteristic of the breed. Dwarf lambs were much smaller than normal, with
      short legs, a domed head with retruded muzzle and protruded mandible, sternal
      deformities and exophthalmic eyes situated more laterally in the face than
      normal. Microscopical examination of long bones of the limbs, bones of the base
      of the skull and vertebrae showed no lesions. Bones from four affected lambs and
      one control lamb were macerated for morphometric examination. Although the length
      of the spinal cord was similar, there was disproportionate shortening of the
      appendicular bones, particularly the distal segments. Thus the disease was
      defined as a skeletal dysplasia characterized by craniofacial deformity and
      disproportionate dwarfism. It is suggested that the disease is inherited as an
      incomplete dominant trait. The shortened face, which is a feature of the Cabugi
      breed, may represent the heterozygous state and the more severe, often lethal,
      dwarfism may occur in homozygotes.

PMID- 24447572
TI  - Comparative virulence of reproductive diseases caused by type 1 (European-like)
      and type 2 (North American-like) porcine reproductive and respiratory syndrome
      virus in experimentally infected pregnant gilts.
AB  - The aim of this study was to compare the virulence of type 1 and type 2 porcine
      reproductive and respiratory syndrome virus (PRRSV) as assessed by the level of
      viral replication, viral distribution and apoptosis in stillborn fetuses and live
      born piglets from infected pregnant gilts. Type 1 or type 2 PRRSV was given
      intranasally to pregnant gilts at 3 weeks before the expected date of
      parturition. Regardless of virus genotype, PRRSV-infected gilts farrowed between
      102 and 109 days of gestation, while control uninfected gilts carried the
      pregnancy to term and farrowed at 114-115 days of gestation. There were no
      significant differences in the mean number of virus-infected cells per unit area
      of tissue when type 1 and type 2 virus infections were compared between stillborn
      fetuses and live-born piglets. Stillborn fetuses from the type 1 PRRSV-infected
      pregnant gilts had a significantly higher mean number of apoptotic cells per unit
      area of thymus (P = 0.013) than those from type 2 PRRSV-infected pregnant gilts.
      Significant differences in virulence were not observed between types 1 and 2
      PRRSV in terms of female reproductive failure, although thymic apoptosis differed
      in stillborn fetuses from type 1 and type 2 PRRSV-infected pregnant gilts.

PMID- 24447573
TI  - Reply to Gianluca Giannarini, Nazareno Suardi and Alberto Briganti's letter to
      the editor re: Prasanna Sooriakumaran, Abhishek Srivastava, Shahrokh F. Shariat,
      et al. A multinational, multi-institutional study comparing positive surgical
      margin rates among 22 393 open, laparoscopic, and robot-assisted radical
      prostatectomy patients. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2013.11.018.

PMID- 24447574
TI  - Re: Prasanna Sooriakumaran, Abhishek Srivastava, Shahrokh F. Shariat, et al. A
      multinational, multi-institutional study comparing positive surgical margin rates
      among 22,393 open, laparoscopic, and robot-assisted radical prostatectomy
      patients. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.11.018.

PMID- 24447575
TI  - Predicting biochemical recurrence following salvage radiotherapy: applying
      lessons learned from primary radiotherapy.

PMID- 24447576
TI  - Expression of serum amyloid A in uterine cervical cancer.
AB  - BACKGROUND: As an acute-phase protein, serum amyloid A (SAA) is expressed
      primarily in the liver. However, its expression in extrahepatic tissues,
      especially in tumor tissues, was also demonstrated recently. In our study, we
      investigated the expression of SAA in uterine cervical carcinomas, and our
      results suggested its potential as a serum biomarker. METHODS: Quantitative real
      time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and enzyme
      linked immunosorbent assay (ELISA) were used to evaluate the SAA gene and protein
      expression levels in the tissues and sera of patients with non-neoplastic lesions
      (NNLs), cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC).
      RESULTS: Compared with NNLs, the SAA gene (SAA1 and SAA4) expression levels were
      significantly higher in uterine CC (mean copy numbers: 138.7 vs. 5.01, P < 0.000;
      and 1.8 vs. 0.079, P = 0.001, respectively) by real-time PCR. IHC revealed
      cytoplasmic SAA protein staining in tissues from adenocarcinoma and squamous cell
      carcinoma of the cervix. The median serum concentrations (MUg/ml) of SAA were
      6.02 in patients with NNLs and 10.98 in patients with CIN (P = 0.31). In
      contrast, the median serum SAA concentration was 23.7 MUg/ml in uterine CC
      patients, which was significantly higher than the SAA concentrations of the NNL
      group (P = 0.002) and the CIN group (P = 0.024). CONCLUSIONS: Our data suggested
      that SAA might be a uterine CC cell product. High SAA concentrations in the serum
      of CC patients may have a role in monitoring disease occurrence and could have
      therapeutic applications. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1433263219102962.

PMID- 24447577
TI  - Monitoring human babesiosis emergence through vector surveillance New England,
      USA.
AB  - Human babesiosis is an emerging tick-borne disease caused by the
      intraerythrocytic protozoan Babesia microti. Its geographic distribution is more
      limited than that of Lyme disease, despite sharing the same tick vector and
      reservoir hosts. The geographic range of babesiosis is expanding, but knowledge
      of its range is incomplete and relies exclusively on reports of human cases. We
      evaluated the utility of tick-based surveillance for monitoring disease expansion
      by comparing the ratios of the 2 infections in humans and ticks in areas with
      varying B. microti endemicity. We found a close association between human disease
      and tick infection ratios in long-established babesiosis-endemic areas but a
      lower than expected incidence of human babesiosis on the basis of tick infection
      rates in new disease-endemic areas. This finding suggests that babesiosis at
      emerging sites is underreported. Vector-based surveillance can provide an early
      warning system for the emergence of human babesiosis.

PMID- 24447579
TI  - Pituitary abscess: report of two cases and literature review.

PMID- 24447578
TI  - Global numbers of infection and disease burden of soil transmitted helminth
      infections in 2010.
AB  - BACKGROUND: Quantifying the burden of parasitic diseases in relation to other
      diseases and injuries requires reliable estimates of prevalence for each disease
      and an analytic framework within which to estimate attributable morbidity and
      mortality. Here we use data included in the Global Atlas of Helminth Infection to
      derive new global estimates of numbers infected with intestinal nematodes (soil
      transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the
      hookworms) and use disability-adjusted life years (DALYs) to estimate disease
      burden. METHODS: Prevalence data for 6,091 locations in 118 countries were
      sourced and used to estimate age-stratified mean prevalence for sub-national
      administrative units via a combination of model-based geostatistics (for sub
      Saharan Africa) and empirical approaches (for all other regions). Geographical
      variation in infection prevalence within these units was approximated using
      modelled logit-normal distributions, and numbers of individuals with infection
      intensities above given thresholds estimated for each species using negative
      binomial distributions and age-specific worm/egg burden thresholds. Finally, age
      stratified prevalence estimates for each level of infection intensity were
      incorporated into the Global Burden of Disease Study 2010 analytic framework to
      estimate the global burden of morbidity and mortality associated with each STH
      infection. RESULTS: Globally, an estimated 438.9 million people (95% Credible
      Interval (CI), 406.3 - 480.2 million) were infected with hookworm in 2010, 819.0
      million (95% CI, 771.7 - 891.6 million) with A. lumbricoides and 464.6 million
      (95% CI, 429.6 - 508.0 million) with T. trichiura. Of the 4.98 million years
      lived with disability (YLDs) attributable to STH, 65% were attributable to
      hookworm, 22% to A. lumbricoides and the remaining 13% to T. trichiura. The vast
      majority of STH infections (67%) and YLDs (68%) occurred in Asia. When
      considering YLDs relative to total populations at risk however, the burden
      distribution varied more considerably within major global regions than between
      them. CONCLUSION: Improvements in the cartography of helminth infection, combined
      with mathematical modelling approaches, have resulted in the most comprehensive
      contemporary estimates for the public health burden of STH. These numbers form an
      important benchmark upon which to evaluate future scale-up of major control
      efforts.

PMID- 24447580
TI  - Purinergic responses of calcium-dependent signaling pathways in cultured adult
      human astrocytes.
AB  - BACKGROUND: The properties of Ca2+ signaling mediated by purinergic receptors are
      intrinsically linked with functional activity of astrocytes. At present little is
      known concerning Ca2+-dependent purinergic responses in adult human astrocytes.
      This work has examined effects of purinergic stimulation to alter levels of
      intracellular Ca2+ in adult human astrocytes. Ca2+-sensitive spectrofluorometry
      was carried out to determine mobilization of intracellular Ca2+ following
      adenosine triphosphate (ATP) or 3'-O-(4-benzoyl)benzoyl-ATP (Bz-ATP) stimulation
      of adult human astrocytes. In some experiments pharmacological modulation of Ca2+
      pathways was applied to help elucidate mechanisms of Ca2+ signaling. RT-PCR was
      also performed to confirm human astrocyte expression of specific purinoceptors
      which were indicated from imaging studies. RESULTS: The endogenous P2 receptor
      agonist ATP (at 100 MUM or 1 mM) applied in physiological saline solution (PSS)
      evoked a rapid increase of [Ca2+]i to a peak amplitude with the decay phase of
      response exhibiting two components. The two phases of decay consisted of an
      initial rapid component which was followed by a secondary slower component. In
      the presence of Ca2+-free solution, the secondary phase of decay was absent
      indicating this prolonged component was due to influx of Ca2+. This prolonged
      phase of decay was also attenuated with the store-operated channel (SOC)
      inhibitor gadolinium (at 2 MUM) added to standard PSS, suggesting this component
      was mediated by SOC activation. These results are consistent with ATP activation
      of P2Y receptor (P2YR) in adult human astrocytes leading to respective rapid
      [Ca2+]i mobilization from intracellular stores followed by Ca2+ entry through
      SOC. An agonist for P2X7 receptor (P2X7R), BzATP induced a very different
      response compared with ATP whereby BzATP (at 300 MUM) elicited a slowly rising
      increase in [Ca2+]i to a plateau level which was sustained in duration. The BzATP
      induced increase in [Ca2+]i was not enhanced with lipopolysaccharide pre
      treatment of cells as previously found for P2X7R mediated response in human
      microglia. RT-PCR analysis showed that adult human astrocytes in vitro
      constitutively express mRNA for P2Y1R, P2Y2R and P2X7R. CONCLUSION: These results
      suggest that activation of metabotropic P2YR (P2Y1R and/or P2Y2R) and ionotropic
      P2X7R could mediate purinergic responses in adult human astrocytes.

PMID- 24447581
TI  - What next for phosphodiesterase inhibitor failures?

PMID- 24447582
TI  - Nasopharyngeal bacterial interactions in children.

PMID- 24447583
TI  - Repeated fear-induced diurnal rhythm disruptions predict PTSD-like sensitized
      physiological acute stress responses in F344 rats.
AB  - AIM: To identify objective factors that can predict future sensitized stress
      responses, thus allowing for effective intervention prior to developing
      sensitization and subsequent stress-related disorders, including post-traumatic
      stress disorder (PTSD). METHODS: Adult male F344 rats implanted with biotelemetry
      devices were exposed to repeated conditioned fear or control conditions for 22
      days followed by exposure to either no, mild or severe acute stress on day 23.
      Diurnal rhythms of locomotor activity (LA), heart rate (HR) and core body
      temperature (CBT) were biotelemetrically monitored throughout the study. In a
      subset of rat not implanted, corticosterone and indices of chronic stress were
      measured immediately following stress. RESULTS: Rats exposed to repeated fear had
      fear-evoked increases in behavioural freezing and HR/CBT during exposure to the
      fear environment and displayed indices of chronic stress. Repeated fear produced
      flattening of diurnal rhythms in LA, HR and CBT. Repeated fear did not sensitize
      the corticosterone response to acute stress, but produced sensitized HR/CBT
      responses following acute stress, relative to the effect of acute stress in the
      absence of a history of repeated fear. Greater diurnal rhythm disruptions during
      repeated fear predicted sensitized acute stress-induced physiological responses.
      Rats exposed to repeated fear also displayed flattened diurnal LA and basal
      increases in HR. CONCLUSIONS: Exposure to repeated fear produces outcomes
      consistent with those observed in PTSD. The results suggest that diurnal rhythm
      disruptions during chronic stressors may help predict sensitized physiological
      stress responses following traumatic events. Monitoring diurnal disruptions
      during repeated stress may thus help predict susceptibility to PTSD.

PMID- 24447584
TI  - miR-200b as a prognostic factor in breast cancer targets multiple members of RAB
      family.
AB  - BACKGROUND: miR-200b has been reported to be a tumor suppressor and a promising
      therapeutic target in cancer. miR-200b has been associated with epithelial
      mesenchymal transition and chemo-resistance in cancer. The aim of this study is
      to investigate the expression of miR-200b, its prognostic roles and its potential
      targets in breast cancer. METHODS: qRT-PCR was used to detect miR-200b expression
      in breast cancer tissues and cell lines. In situ hybridization of miR-200b on
      tissue microarray including 134 breast cancer samples was used to evaluate its
      prognostic role. Novel targets of miR-200b in breast cancer were predicted and
      confirmed by luciferase reporter assay and western bloting. Immunohistochemical
      staining was used for protein detection. The biological effects of miR-200b in
      breast cancer cells were further confirmed by ectopic expression of its mimics
      followed by MTT assay and invasion test. RESULTS: miR-200b was downregulated in
      breast cancer tissues and cell lines and its low-expression correlated with poor
      outcome in breast cancer patients. Members of RAB family, RAB21, RAB23, RAB18 and
      RAB3B were predicted to be the targets of miR-200b. The luciferase reporter assay
      was performed to certificate this prediction. The expressions of RAB21, RAB23,
      RAB18 and RAB3B were suppressed by transfection of miR-200b in breast cancer
      cells. Over-expression of miR-200b or knock-down of RAB21, RAB23, RAB18 and RAB3B
      inhibited breast cancer cell proliferation and invasion in vitro. CONCLUSIONS:
      Our study provides evidence that miR-200b is a prognostic factor in breast cancer
      targeting multiple members of RAB family. MiR-200b could be a potential
      therapeutic target in breast cancer.

PMID- 24447585
TI  - Two programmed replicative lifespans of Saccharomyces cerevisiae formed by the
      endogenous molecular-cellular network.
AB  - Cellular replicative capacity is a therapeutic target for regenerative medicine
      as well as cancer treatment. The mechanism of replicative senescence and cell
      immortality is still unclear. We investigated the diauxic growth of Saccharomyces
      cerevisiae and demonstrate that the replicative capacity revealed by the yeast
      growth curve can be understood by using the dynamical property of the molecular
      cellular network regulating S. cerevisiae. The endogenous network we proposed has
      a limit cycle when pheromone signaling is disabled, consistent with the
      exponential growth phase with an infinite replicative capacity. In the post
      diauxic phase, the cooperative effect of the pheromone activated mitogen
      activated protein kinase (MAPK) signaling pathway with the cell cycle leads to a
      fixed point attractor instead of the limit cycle. The cells stop dividing after
      several generations counting from the beginning of the post-diauxic growth. By
      tuning the MAPK pathway, S. cerevisiae therefore programs the number of
      offsprings it replicates. 

PMID- 24447586
TI  - A simple model of NF-kappaB dynamics reproduces experimental observations.
AB  - The mathematical modeling of the NF-kappaB oscillations has attracted
      considerable attention in recent times, but there is a lack of simple models in
      the literature that can capture the main features of the dynamics of this
      important transcription factor. For this reason we propose a simple model that
      summarizes the key steps of the NF-kappaB pathway. We show that the resulting 5
      dimensional dynamical system can reproduce different phenomena observed in
      experiments. Our model can display smooth and spiky oscillations in the amount of
      nuclear NF-kappaB and can reproduce the variety of dynamics observed when
      different stimulations such as TNF-alpha and LPS are used. Furthermore we show
      that the model can be easily extended to reproduce the expression of early,
      intermediate and late genes upon stimulation. As a final example we show that our
      simple model can mimic the different transcriptional outputs observed when cells
      are treated with two different drugs leading to nuclear localization of NF
      kappaB: Leptomycin B and Cycloheximide. 

PMID- 24447587
TI  - Associations of high sensitivity C-reactive protein levels with the prevalence of
      asymptomatic intracranial arterial stenosis.
AB  - BACKGROUND AND PURPOSE: High sensitivity C-reactive protein (hs-CRP), an
      inflammatory biomarker, has been demonstrated to contribute to the process of
      atherosclerosis and artery stenosis. The aim of this study was to evaluate
      whether hs-CRP level is associated with asymptomatic intracranial artery stenosis
      (ICAS). METHODS: A random sample of 5440 participants aged 40 years or older
      (40.1% women) were enrolled in the Asymptomatic Polyvascular Abnormalities
      Community study in 2010-2011. Information on the potential risk factors for ICAS
      was collected and the presence of ICAS was assessed by transcranial Doppler in
      5309 participants. Participants were stratified into three groups according to hs
      CRP levels. A multivariate logistic regression was used to examine the
      association between hs-CRP levels and asymptomatic ICAS. RESULTS: The prevalence
      of asymptomatic ICAS was 13.2% in this cohort. The median of hs-CRP levels was
      positively associated with the increasing numbers of ICASs. After adjusting for
      possible risk factors, hs-CRP >= 3 mg/l remained significantly associated with
      asymptomatic ICAS (odds ratio 1.28, 95% confidence interval 1.02-1.61).
      CONCLUSIONS: In this large community-based study, subjects with higher hs-CRP
      levels showed a mild increase in the prevalence of asymptomatic ICAS, independent
      of traditional vascular risk factors. hs-CRP is an independent predictor of
      asymptomatic ICAS and intracranial atherosclerotic burden.

PMID- 24447588
TI  - An argument against the focus on community resilience in public health.
AB  - BACKGROUND: It has been suggested that Public Health professionals focus on
      community resilience in tackling chronic problems, such as poverty and
      deprivation; is this approach useful? DISCUSSION: Resilience is always i) of
      something ii) to something iii) to an endpoint, as in i) a rubber ball, ii) to a
      blunt force, iii) to its original shape. "Community resilience" might be: of a
      neighbourhood, to a flu pandemic, with the endpoint, to return to normality. In
      these two examples, the endpoint is as-you-were. This is unsuitable for some
      examples of resilience. A child that is resilient to an abusive upbringing has an
      endpoint of living a happy life despite that upbringing: this is an as-you-should
      be endpoint. Similarly, a chronically deprived community cannot have the endpoint
      of returning to chronic deprivation: so what is its endpoint? Roughly, it is an
      as-you-should-be endpoint: to provide an environment for inhabitants to live
      well. Thus resilient communities will be those that do this in the face of
      challenges. How can they be identified?One method uses statistical outliers,
      neighbourhoods that do better than would be expected on a range of outcomes given
      a range of stressors. This method tells us that a neighbourhood is resilient but
      not why it is. In response, a number of researchers have attributed
      characteristics to resilient communities; however, these generally fail to
      distinguish characteristics of a good community from those of a resilient one.
      Making this distinction is difficult and we have not seen it successfully done;
      more importantly, it is arguably unnecessary.There already exist approaches in
      Public Health to assessing and developing communities faced with chronic
      problems, typically tied to notions such as Social Capital. Community resilience
      to chronic problems, if it makes sense at all, is likely to be a property that
      emerges from the various assets in a community such as human capital, built
      capital and natural capital. SUMMARY: Public Health professionals working with
      deprived neighbourhoods would be better to focus on what neighbourhoods have or
      could develop as social capital for living well, rather than on the vague and
      tangential notion of community resilience.

PMID- 24447589
TI  - The gill chamber epibiosis of deep-sea shrimp Rimicaris exoculata: an in-depth
      metagenomic investigation and discovery of Zetaproteobacteria.
AB  - The gill chamber of deep-sea hydrothermal vent shrimp Rimicaris exoculata hosts a
      dense community of epibiotic bacteria dominated by filamentous
      Epsilonproteobacteria and Gammaproteobacteria. Using metagenomics on shrimp from
      the Rainbow hydrothermal vent field, we showed that both epibiont groups have the
      potential to grow autotrophically and oxidize reduced sulfur compounds or
      hydrogen with oxygen or nitrate. For carbon fixation, the Epsilonproteobacteria
      use the reductive tricarboxylic acid cycle, whereas the Gammaproteobacteria use
      the Calvin-Benson-Bassham cycle. Only the epsilonproteobacterial epibionts had
      the genes necessary for producing ammonium. This ability likely minimizes direct
      competition between epibionts and also broadens the spectrum of environmental
      conditions that the shrimp may successfully inhabit. We identified genes likely
      to be involved in shrimp-epibiont interactions, as well as genes for nutritional
      and detoxification processes that might benefit the host. Shrimp epibionts at
      Rainbow are often coated with iron oxyhydroxides, whose origin is intensely
      debated. We identified 16S rRNA sequences and functional genes affiliated with
      iron-oxidizing Zetaproteobacteria, which indicates that biological iron oxidation
      might play a role in forming these deposits. Fluorescence in situ hybridizations
      confirmed the presence of active Zetaproteobacteria in the R. exoculata gill
      chamber, thus providing the first evidence for a Zetaproteobacteria-invertebrate
      association. 

PMID- 24447590
TI  - A simulation study into the performance of "optimal" diagnostic thresholds in the
      population:"Large" effect sizes are not enough.
AB  - OBJECTIVES: Many diagnostic studies are aimed at defining "optimal" thresholds.
      Here, we evaluate the performance of empirically defined optimal thresholds (1)
      in the sample in which they were defined and (2) in the population from which the
      sample was drawn. STUDY DESIGN AND SETTING: We simulated test results for 120,000
      samples varying the number of people without a disease (n between 20 and 500),
      number of people with a disease (m between 20 and 500), the magnitude of the
      difference between group means [effect size (ES) between 0.5 and 4], and
      distributions (normal and log-normal). The thresholds associated with the maximal
      Youden index were defined as optimal. Performance was defined as the percentage
      of correct classifications in the sample and when applied to the whole
      population. RESULTS: At the population level, the thresholds defined for the four
      ESs (0.5, 0.8, 2, and 4) yielded a median of 59%, 65%, 83%, and 97% correct
      classifications, respectively. At the sample level, the samples with similar
      characteristics yielded widely varying estimates of the performance that were
      systematically higher than at the population level. CONCLUSION: Researchers need
      to be careful defining cut points for mean differences that are traditionally
      considered "large" (ES = 0.8). The diagnostic utility of optimal thresholds needs
      to be assessed in prospective studies.

PMID- 24447591
TI  - The minimal clinically important difference determined using item response theory
      models: an attempt to solve the issue of the association with baseline score.
AB  - OBJECTIVES: Determining the minimal clinically important difference (MCID) of
      questionnaires on an interval scale, the trait level (TL) scale, using item
      response theory (IRT) models could overcome its association with baseline
      severity. The aim of this study was to compare the sensitivity (Se), specificity
      (Sp), and predictive values (PVs) of the MCID determined on the score scale (MCID
      Sc) or the TL scale (MCID-TL). STUDY DESIGN AND SETTING: The MCID-Sc and MCID-TL
      of the MOS-SF36 general health subscale were determined for deterioration and
      improvement on a cohort of 1,170 patients using an anchor-based method and a
      partial credit model. The Se, Sp, and PV were calculated using the global rating
      of change (the anchor) as the gold standard test. RESULTS: The MCID-Sc magnitude
      was smaller for improvement (1.58 points) than for deterioration (-7.91 points).
      The Se, Sp, and PV were similar for MCID-Sc and MCID-TL in both cases. However,
      if the MCID was defined on the score scale as a function of a range of baseline
      scores, its Se, Sp, and PV were consistently higher. CONCLUSION: This study
      reinforces the recommendations concerning the use of an MCID-Sc defined as a
      function of a range of baseline scores.

PMID- 24447592
TI  - Estimating a test's accuracy using tailored meta-analysis-How setting-specific
      data may aid study selection.
AB  - OBJECTIVES: To determine a plausible estimate for a test's performance in a
      specific setting using a new method for selecting studies. STUDY DESIGN AND
      SETTING: It is shown how routine data from practice may be used to define an
      "applicable region" for studies in receiver operating characteristic space. After
      qualitative appraisal, studies are selected based on the probability that their
      study accuracy estimates arose from parameters lying in this applicable region.
      Three methods for calculating these probabilities are developed and used to
      tailor the selection of studies for meta-analysis. The Pap test applied to the UK
      National Health Service (NHS) Cervical Screening Programme provides a case
      example. RESULTS: The meta-analysis for the Pap test included 68 studies, but at
      most 17 studies were considered applicable to the NHS. For conventional meta
      analysis, the sensitivity and specificity (with 95% confidence intervals) were
      estimated to be 72.8% (65.8, 78.8) and 75.4% (68.1, 81.5) compared with 50.9%
      (35.8, 66.0) and 98.0% (95.4, 99.1) from tailored meta-analysis using a binomial
      method for selection. Thus, for a cervical intraepithelial neoplasia (CIN) 1
      prevalence of 2.2%, the post-test probability for CIN 1 would increase from 6.2%
      to 36.6% between the two methods of meta-analysis. CONCLUSION: Tailored meta
      analysis provides a method for augmenting study selection based on the study's
      applicability to a setting. As such, the summary estimate is more likely to be
      plausible for a setting and could improve diagnostic prediction in practice.

PMID- 24447593
TI  - Urotensin II inhibited the proliferation of cardiac side population cells in mice
      during pressure overload by JNK-LRP6 signalling.
AB  - Cardiac side population cells (CSPs) are promising cell resource for the
      regeneration in diseased heart as intrinsic cardiac stem cells. However, the
      relative low ratio of CSPs in the heart limited the ability of CSPs to repair
      heart and improve cardiac function effectively under pathophysiological
      condition. Which factors limiting the proliferation of CSPs in diseased heart are
      unclear. Here, we show that urotensin II (UII) regulates the proliferation of
      CSPs by c-Jun N-terminal kinase (JNK) and low density lipoprotein receptor
      related protein 6 (LRP6) signalling during pressure overload. Pressure overload
      greatly upregulated UII level in plasma, UII receptor (UT) antagonist, urantide,
      promoted CSPs proliferation and improved cardiac dysfunction during chronic
      pressure overload. In cultured CSPs subjected to mechanical stretch (MS), UII
      significantly inhibited the proliferation by UT. Nanofluidic proteomic
      immunoassay showed that it is the JNK activation, but not the extracellular
      signal-regulated kinase signalling, that involved in the UII-inhibited-
      proliferation of CSPs during pressure overload. Further analysis in vitro
      indicated UII-induced-phospho-JNK regulates phosphorylation of LRP6 in cultured
      CSPs after MS, which is important in the inhibitory effect of UII on the CSPs
      during pressure overload. In conclusion, UII inhibited the proliferation of CSPs
      by JNK/LRP6 signalling during pressure overload. Pharmacological inhibition of
      UII promotes CSPs proliferation in mice, offering a possible therapeutic approach
      for cardiac failure induced by pressure overload. 

PMID- 24447595
TI  - Impact of point-of-care CD4 testing on linkage to HIV care: a systematic review.
AB  - INTRODUCTION: Point-of-care testing for CD4 cell count is considered a promising
      way of reducing the time to eligibility assessment for antiretroviral therapy
      (ART) and of increasing retention in care prior to treatment initiation. In this
      review, we assess the available evidence on the patient and programme impact of
      point-of-care CD4 testing. METHODS: We searched nine databases and two conference
      sites (up until 26 October 2013) for studies reporting patient and programme
      outcomes following the introduction of point-of-care CD4 testing. Where
      appropriate, results were pooled using random-effects methods. RESULTS: Fifteen
      studies, mainly from sub-Saharan Africa, were included for review, providing
      evidence for adults, adolescents, children and pregnant women. Compared to
      conventional laboratory-based testing, point-of-care CD4 testing increased the
      likelihood of having CD4 measured [odds ratio (OR) 4.1, 95% CI 3.5-4.9, n=2] and
      receiving a CD4 result (OR 2.8, 95% CI 1.5-5.6, n=6). Time to being tested was
      significantly reduced, by a median of nine days; time from CD4 testing to
      receiving the result was reduced by as much as 17 days. Evidence for increased
      treatment initiation was mixed. DISCUSSION: The results of this review suggest
      that point-of-care CD4 testing can increase retention in care prior to starting
      treatment and can also reduce time to eligibility assessment, which may result in
      more eligible patients being initiated on ART.

PMID- 24447597
TI  - The effects of dual tasking on handwriting in patients with Parkinson's disease.
AB  - Previous studies have shown that patients with Parkinson's disease (PD)
      experience extensive problems during dual tasking. Up to now, dual-task
      interference in PD has mainly been investigated in the context of gait research.
      However, the simultaneous performance of two different tasks is also a
      prerequisite to efficiently perform many other tasks in daily life, including
      upper limb tasks. To address this issue, this study investigated the effect of a
      secondary cognitive task on the performance of handwriting in patients with PD.
      Eighteen PD patients and 11 age-matched controls performed a writing task
      involving the production of repetitive loops under single- and dual-task
      conditions. The secondary task consisted of counting high and low tones during
      writing. The writing tests were performed with two amplitudes (0.6 and 1.0cm)
      using a writing tablet. Results showed that dual-task performance was affected in
      PD patients versus controls. Dual tasking reduced writing amplitude in PD
      patients, but not in healthy controls (p=0.046). Patients' writing size was
      mainly reduced during the small-amplitude condition (small amplitude p=0.017;
      large amplitude p=0.310). This suggests that the control of writing at small
      amplitudes requires more compensational brain-processing recourses in PD and is
      as such less automatic than writing at large amplitudes. In addition, there was a
      larger dual-task effect on the secondary task in PD patients than controls
      (p=0.025). The writing tests on the writing tablet proved highly correlated to
      daily life writing as measured by the 'Systematic Screening of Handwriting
      Difficulties' test (SOS-test) and other manual dexterity tasks, particularly
      during dual-task conditions. Taken together, these results provide additional
      insights into the motor control of handwriting and the effects of dual tasking
      during upper limb movements in patients with PD. 

PMID- 24447594
TI  - Bioinformatic analysis of beta carbonic anhydrase sequences from protozoans and
      metazoans.
AB  - BACKGROUND: Despite the high prevalence of parasitic infections, and their impact
      on global health and economy, the number of drugs available to treat them is
      extremely limited. As a result, the potential consequences of large-scale
      resistance to any existing drugs are a major concern. A number of recent
      investigations have focused on the effects of potential chemical inhibitors on
      bacterial and fungal carbonic anhydrases. Among the five classes of carbonic
      anhydrases (alpha, beta, gamma, delta and zeta), beta carbonic anhydrases have
      been reported in most species of bacteria, yeasts, algae, plants, and particular
      invertebrates (nematodes and insects). To date, there has been a lack of
      knowledge on the expression and molecular structure of beta carbonic anhydrases
      in metazoan (nematodes and arthropods) and protozoan species. METHODS: Here, the
      identification of novel beta carbonic anhydrases was based on the presence of the
      highly-conserved amino acid sequence patterns of the active site. A phylogenetic
      tree was constructed based on codon-aligned DNA sequences. Subcellular
      localization prediction for each identified invertebrate beta carbonic anhydrase
      was performed using the TargetP webserver. RESULTS: We verified a total of 75
      beta carbonic anhydrase sequences in metazoan and protozoan species by proteome
      wide searches and multiple sequence alignment. Of these, 52 were novel, and
      contained highly conserved amino acid residues, which are inferred to form the
      active site in beta carbonic anhydrases. Mitochondrial targeting peptide analysis
      revealed that 31 enzymes are predicted with mitochondrial localization; one was
      predicted to be a secretory enzyme, and the other 43 were predicted to have other
      undefined cellular localizations. CONCLUSIONS: These investigations identified 75
      beta carbonic anhydrases in metazoan and protozoan species, and among them there
      were 52 novel sequences that were not previously annotated as beta carbonic
      anhydrases. Our results will not only change the current information in
      proteomics and genomics databases, but will also suggest novel targets for drugs
      against parasites.

PMID- 24447596
TI  - Changes in the brain and plasma Abeta peptide levels with age and its
      relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of
      Alzheimer's disease.
AB  - Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and
      mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are
      widely used in experimental studies. In the present work, the relationships
      between brain and plasma amyloid-beta peptide (Abeta) levels and cognitive
      impairments were examined in male APPswe/PS1dE9 double transgenic mice at
      different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice
      exhibited significant learning deficits from the age of 6months (M6), which were
      aggravated at later stages of life (M8 and M12). Sporadic brain amyloid plaques
      were observed in mice as early as M3 and progressively increased in number and
      size up to M12. A similar increase was observed in brain insoluble Abeta levels
      as assessed by enzyme-linked immunosorbent assay (ELISA). In particular, the
      levels of brain insoluble Abeta peptides rose steeply from M4 to M6.
      Interestingly, this pronounced amyloid deposition was accompanied by a temporary
      fall in the concentration of brain soluble and membrane-bound Abeta peptides at
      M6 that rose again at M8 and M12. The plasma levels of Abeta40 and Abeta42
      decreased with advancing age up to M8, when they stabilized at M12. This decrease
      in plasma Abeta levels coincided with the observed increase in insoluble brain
      Abeta levels. These results could be useful for developing plasma Abeta levels as
      possible biomarkers of the cerebral amyloidosis and provide advances in the
      knowledge of the Abeta peptide biochemical changes that occur in the brain of
      Alzheimer's disease patients. 

PMID- 24447598
TI  - Spontaneous neuronal activity predicts intersubject variations in executive
      control of attention.
AB  - Executive control of attention regulates our thoughts, emotion and behavior.
      Individual differences in executive control are associated with task-related
      differences in brain activity. But it is unknown whether attentional differences
      depend on endogenous (resting state) brain activity and to what extent regional
      fluctuations and functional connectivity contribute to individual variations in
      executive control processing. Here, we explored the potential contribution of
      intrinsic brain activity to executive control by using resting-state functional
      magnetic resonance imaging (fMRI). Using the amplitude of low-frequency
      fluctuations (ALFF) as an index of spontaneous brain activity, we found that ALFF
      in the right precuneus (PCUN) and the medial part of left superior frontal gyrus
      (msFC) was significantly correlated with the efficiency of executive control
      processing. Crucially, the strengths of functional connectivity between the right
      PCUN/left msFC and distributed brain regions, including the left fusiform gyrus,
      right inferior frontal gyrus, left superior frontal gyrus and right precentral
      gyrus, were correlated with individual differences in executive performance.
      Together, the ALFF and functional connectivity accounted for 67% of the
      variability in behavioral performance. Moreover, the strength of functional
      connectivity between specific regions could predict more individual variability
      in executive control performance than regionally specific fluctuations. In
      conclusion, our findings suggest that spontaneous brain activity may reflect or
      underpin executive control of attention. It will provide new insights into the
      origins of inter-individual variability in human executive control processing. 

PMID- 24447599
TI  - Laboratory-acquired buffalopox virus infection, India.

PMID- 24447600
TI  - Why the MDGs need good governance in pharmaceutical systems to promote global
      health.
AB  - BACKGROUND: Corruption in the health sector can hurt health outcomes. Improving
      good governance can in turn help prevent health-related corruption. We understand
      good governance as having the following characteristics: it is consensus
      oriented, accountable, transparent, responsive, equitable and inclusive,
      effective and efficient, follows the rule of law, is participatory and should in
      theory be less vulnerable to corruption. By focusing on the pharmaceutical
      system, we explore some of the key lessons learned from existing initiatives in
      good governance. As the development community begins to identify post-2015
      Millennium Development Goals targets, it is essential to evaluate programs in
      good governance in order to build on these results and establish sustainable
      strategies. This discussion on the pharmaceutical system illuminates why.
      DISCUSSION: Considering pharmaceutical governance initiatives such as those
      launched by the World Bank, World Health Organization, and the Global Fund, we
      argue that country ownership of good governance initiatives is essential but also
      any initiative must include the participation of impartial stakeholders.
      Understanding the political context of any initiative is also vital so that
      potential obstacles are identified and the design of any initiative is flexible
      enough to make adjustments in programming as needed. Finally, the inherent
      challenge which all initiatives face is adequately measuring outcomes from any
      effort. However in fairness, determining the precise relationship between good
      governance and health outcomes is rarely straightforward. SUMMARY: Challenges
      identified in pharmaceutical governance initiatives manifest in different forms
      depending on the nature and structure of the initiative, but their regular
      occurrence and impact on population-based health demonstrates growing importance
      of addressing pharmaceutical governance as a key component of the post-2015
      Millennium Development Goals. Specifically, these challenges need to be
      acknowledged and responded to with global cooperation and innovation to establish
      localized and evidence-based metrics for good governance to promote global
      pharmaceutical safety.

PMID- 24447601
TI  - Diaphragms of the carotid and vertebral arteries: an under-diagnosed cause of
      ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: Diaphragms of the internal carotid and vertebral arteries
      as a cause of ischaemic stroke are reported and stenting of diaphragms as a
      therapeutic option in stroke secondary prevention is described. METHODS: Five
      patients were cared for in our institution from 2000 to 2011 for recurrent
      ischaemic strokes which were classified to be of undetermined aetiology after
      completion of the usual investigations. Because the patients had already had
      ischaemic strokes in the territory of the same artery, a conventional digital
      subtracted angiography was performed. A diaphragm was identified on the artery
      that supplied the territory in which the stroke occurred. The stroke was
      therefore attributed to the diaphragm. Clinical and radiological data, treatment
      and the clinical course of the patients was retrospectively reviewed. RESULTS:
      The diaphragm was located in the vertebral artery in three cases and in the bulb
      of the internal carotid artery in two. In all cases cerebral MR showed ischaemic
      strokes of different ages downstream of the diaphragm. Stenting was performed in
      four cases. No patient had a symptomatic recurrent ischaemic event after
      stenting. CONCLUSIONS: Diaphragms are a rare cause of recurrent embolic strokes
      which are often not detected with non-invasive imaging. Stenting appears to be a
      therapeutic option in stroke secondary prevention. These observations suggest
      that conventional angiography should be performed in cases of recurrent ischaemic
      strokes in the territory of a single artery and in cases of ischaemic stroke of
      undetermined aetiology in young adults when the usual investigations are
      negative.

PMID- 24447602
TI  - Peripheral spondyloarthritis in a patient with Noonan's syndrome.
AB  - Noonan's syndrome is an autosomal dominant genetic disorder with high phenotypic
      variability, characterized mainly by facial dysmorphism, congenital heart disease
      and short stature. We describe the case of a male patient diagnosed with Noonan's
      syndrome and peripheral spondyloarthritis, a previously undescribed association
      in the literature. 

PMID- 24447603
TI  - Continuing decrease in coronary heart disease mortality in Sweden.
AB  - BACKGROUND: Deaths from coronary heart disease (CHD) have been decreasing in most
      Western countries over the last few decades. In contrast, a flattening of the
      decrease in mortality has been recently reported among younger age groups in some
      countries. We aimed to determine whether the decrease in CHD mortality is
      flattening among Swedish young adults. METHODS: We examined trends in CHD
      mortality in Sweden between 1987 and 2009 among persons aged 35 to 84 years using
      CHD mortality data from the Swedish National Register on Cause of Death. Annual
      percent changes in rates were examined using Joinpoint software. RESULTS:
      Overall, CHD mortality rates decreased by 67.4% in men and 65.1% in women. Among
      men aged 35-54 years, there was a modest early attenuation from a marked initial
      decrease. In the oldest women aged 75-84 years, an attenuation in the mortality
      decrease was observed from 1989 to 1992, followed by a decrease, as in all other
      age groups. CONCLUSIONS: In Sweden, coronary heart disease deaths are still
      falling. We were unable to confirm a flattening of the decline in young people.
      Death rates continue to decline in men and women across all age groups, albeit at
      a slower pace in younger men since 1991. Continued careful monitoring of CHD
      mortality trends in Sweden is required, particularly among young adults.

PMID- 24447604
TI  - Spontaneous resolution of large acute subdural hematoma and the value of
      neurological exam in conservative management of high risk patients.

PMID- 24447605
TI  - Lymphocytic choriomeningitis virus in employees and mice at multipremises feeder
      rodent operation, United States, 2012.
AB  - We investigated the extent of lymphocytic choriomeningitis virus (LCMV) infection
      in employees and rodents at 3 commercial breeding facilities. Of 97 employees
      tested, 31 (32%) had IgM and/or IgG to LCMV, and aseptic meningitis was diagnosed
      in 4 employees. Of 1,820 rodents tested in 1 facility, 382 (21%) mice (Mus
      musculus) had detectable IgG, and 13 (0.7%) were positive by reverse
      transcription PCR; LCMV was isolated from 8. Rats (Rattus norvegicus) were not
      found to be infected. S-segment RNA sequence was similar to strains previously
      isolated in North America. Contact by wild mice with colony mice was the likely
      source for LCMV, and shipments of infected mice among facilities spread the
      infection. The breeding colonies were depopulated to prevent further human
      infections. Future outbreaks can be prevented with monitoring and management, and
      employees should be made aware of LCMV risks and prevention. 

PMID- 24447606
TI  - Detection of the index tumour and tumour volume in prostate cancer using T2
      weighted and diffusion-weighted magnetic resonance imaging (MRI) alone.
AB  - OBJECTIVE: To examine the performance of T2-weighted (T2W) and diffusion-weighted
      (DW) magnetic resonance imaging (MRI) for detecting the index tumour in patients
      with prostate cancer and to examine the agreement between MRI and histology when
      assessing tumour volume (TV) and overall tumour burden. PATIENTS AND METHODS: The
      study included 199 consecutive patients with biopsy confirmed prostate cancer
      randomised to MRI before radical prostatectomy from December 2009 to July 2012.
      MRI-detected tumours (MRTs) were ranked from 1 to 3 according to decreasing
      volume and were compared with histologically detected tumours (HTs) ranked from 1
      to 3, with HT 1 = index tumour. Whole-mount section histology was used as a
      reference standard. The TVs of true-positive MRTs (MRTVs 1-3) were compared with
      the TVs found by histology (HTVs 1-3). All tumours were registered on a 30-sector
      map and by classifying each sector as positive/negative, the rate of true
      positive and -negative sectors was calculated. RESULTS: The detection rate for
      the HT 1 (index tumour) was 92%; HT 2, 45%; and HT 3, 37%. The MRTV 1-3 vs the
      HTV 1-3 were 2.8 mL vs 4.0 mL (index tumour, P < 0.001), 1.0 mL vs 0.9 mL (tumour
      2, P = 0.413), and 0.6 mL vs 0.5 mL (tumour 3, P = 0.492). The rate of true
      positive and -negative sectors was 50% and 88%, kappa = 0.39. CONCLUSION: A
      combination of T2W and DW MRI detects the index tumour in 92% of cases, although
      MRI underestimates both TV and tumour burden compared with histology.

PMID- 24447607
TI  - Clustered precursors in bone marrow sections predict early relapse in patients
      with acute myeloid leukemia within hematologic remission.
AB  - BACKGROUND: Bone marrow (BM) aspiration is largely used for relapse assessment in
      acute myeloid leukemia (AML). It remains unclear what roles that BM trephine
      biopsy plays on relapse assessment. METHODS: Bone marrow (BM) sections during
      complete remission (CR) from 60 acute myeloid leukemia (AML) patients were
      retrospectively analyzed. Computer image processing technology was performed for
      detection of the distance between precursors and endosteum, and density of
      precursors was also calculated under light microscopic image.
      Immunohistochemistry was used to identify the immunophenotype of clustered
      precursors. RESULTS: Except for single and double precursors, there existed
      clustered precursors of 3-5 cells during CR. Here, we demonstrated that clustered
      precursors, but not single and double precursors, were useful in risk factor of
      relapse. Area under the receiving operator curve (ROC) was of 0.007 (CI 95%, from
      0.572 to 0.851). Using a standard cut-off value of >4.0/mm2 for cluster density,
      early relapse was detected with a sensitivity of 51.5% and a specificity of
      85.7%.Multivariate Cox regression analysis revealed that clustered precursor is
      an independent risk factor for early relapse (Adjusted HR: 0.325, 95% CI: 0.156
      0.679, p = 0.003). CONCLUSIONS: Cumulatively, clustered precursors in BM sections
      during CR may serve as an independent risk factor of early relapse and poor
      outcome for AML patients in cluster density > 4.0/mm2 in sections. Early
      aggressive interventions are needed to prevent hematologic relapse.

PMID- 24447609
TI  - Anterior segment angiography of the normal canine eye: a comparison between
      indocyanine green and sodium fluorescein.
AB  - The objective of this study was to assess and compare indocyanine green (IG) and
      sodium fluorescein (SF) angiographic findings in the normal canine anterior
      segment using a digital single lens reflex (dSLR) camera adaptor. Images were
      obtained from 10 brown-eyed Beagles, free of ocular and systemic disease. All
      animals received butorphanol (0.2 mg/kg IM), maropitant citrate (1.0 mg/kg SC)
      and diphenhydramine (2.0 mg/kg SC) 20 min prior to propofol (4 mg/kg IV bolus,
      0.2 mg/kg/min continuous rate infusion). Standard color imaging was performed
      prior to the administration of 0.25% IG (1 mg/kg IV). Imaging was performed using
      a full spectrum dSLR camera, dSLR camera adaptor, camera lens (Canon 60 mm f/2.8
      Macro) and an accessory flash. Images were obtained at a rate of 1/s immediately
      following IG bolus for 30 s, then at 1, 2, 3, 4 and 5 min. Ten minutes later, 10%
      SF (20 mg/kg IV) was administered. Imaging was repeated using the same adaptor
      system and imaging sequence protocol. Arterial, capillary and venous phases were
      identified during anterior segment IG angiography (ASIGA) and their time
      sequences were recorded. ASIGA offered improved visualization of the iris
      vasculature in heavily pigmented eyes compared to anterior segment SF angiography
      (ASSFA), since visualization of the vascular pattern during ASSFA was not
      possible due to pigment masking. Leakage of SF was noted in a total of six eyes.
      The use of IG and SF was not associated with any observed adverse events. The
      adaptor described here provides a cost-effective alternative to existing imaging
      systems.

PMID- 24447608
TI  - Occipital anaplastic oligodendroglioma with multiple organ metastases after a
      short clinical course: a case report and literature review.
AB  - BACKGROUND: It is generally believed that malignant gliomas never metastasize
      outside the central nervous system (CNS). However, the notion that
      oligodendrogliomas (OGDs) cells cannot spread outside CNS is being challenged.
      METHODS: We described in detail the clinical story of one patient with anaplastic
      OGD, which metastasized to lymph nodes, bone marrowand bones Genetic analyses
      included detection of 1p and 19q chromosomal arms, methylation status of MGMT
      promoter, and PTEN exon mutations. A search of worldwide literature was conducted
      for reports of metastatic OGDs using NCBI-PubMed, with the keywords
      "extracranial", "extraneural", "oligodendroglioma", "oligodendrogliomas",
      "metastatic", "metastasis", and "metastases", in different combinations. RESULTS:
      An open biopsy of the infiltrated bones in our patient revealed that malignant
      cells had replaced the patient's marrow. Moreover, the diagnosis of multiple
      organ metastases of anaplastic OGD was confirmed based on immunohistochemical
      staining. Genetic analyses showed that the tumors originated from previously
      resected brain lesions. None of the lesions had 1p and 19q deletions, but
      hypermethylation of MGMT promoter, and the G -> A transversion at codon 234 of
      PTEN exon 2 were detected. Literatures review yielded 60 reports of metastatic
      OGDs from 1951 to the present, which with our patient makes 61 cases. Concerning
      these 61 patients, there were 110 infiltrated sites correlated closely with
      primary OGDs. The most frequent metastatic sites were bone and bone marrow (n =
      47; 42.7%), lymph nodes (n = 22; 20.0%), liver (n = 7; 6.4%), scalp (n = 6;
      5.5%), lung (n = 6; 5.5%), pleura (n = 4; 3.6%), chest wall (n = 3; 2.7%),
      iliopsoas muscle (n = 2; 1.8%), soft tissue (n = 2; 1.8%), and parotid gland (n =
      2; 1.8%). CONCLUSIONS: Extracranial metastases in anaplastic OGD are very rare
      but they do occur; bone and bone marrow may be the most common sites. Detection
      of certain molecular markers such as deletion of 1p and 19q chromosomal arms,
      hypermethylation of MGMT promoter, and characteristic PTEN exon mutations may
      help differentiate subtypes which are more prone to extracranial metastases.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/8749838611478560.

PMID- 24447610
TI  - Evidence of distinct pathways for bacterial degradation of the steroid compound
      cholate suggests the potential for metabolic interactions by interspecies cross
      feeding.
AB  - The distribution and the metabolic pathways of bacteria degrading steroid
      compounds released by eukaryotic organisms were investigated using the bile salt
      cholate as model substrate. Cholate-degrading bacteria could be readily isolated
      from freshwater environments. All isolated strains transiently released steroid
      degradation intermediates into culture supernatants before their further
      degradation. Cholate degradation could be initiated via two different reaction
      sequences. Most strains degraded cholate via a reaction sequence known from the
      model organism Pseudomonas sp. strain Chol1 releasing intermediates with a 3-keto
      Delta(1,4) -diene structure of the steroid skeleton. The actinobacterium Dietzia
      sp. strain Chol2 degraded cholate via a different and yet unexplored reaction
      sequence releasing intermediates with a 3-keto-Delta(4,6) -diene-7-deoxy
      structure of the steroid skeleton such as 3,12-dioxo-4,6-choldienoic acid
      (DOCDA). Using DOCDA as substrate, two Alphaproteobacteria, strains Chol10-11,
      were isolated that produced the same cholate degradation intermediates as strain
      Chol2. With DOCDA as substrate for Pseudomonas sp. strain Chol1 only the side
      chain was degraded while the ring system was transformed into novel steroid
      compounds accumulating as dead-end metabolites. These metabolites could be
      degraded by the DOCDA-producing strains Chol10-11. These results indicate that
      bacteria with potentially different pathways for cholate degradation coexist in
      natural habitats and may interact via interspecies cross-feeding. 

PMID- 24447611
TI  - The direct medical costs of epilepsy in children and young people: a population
      based study of health resource utilisation.
AB  - We described the health resource utilisation (HRU) and associated direct medical
      costs of managing epilepsy in children and young people (CYP) using population
      level data from the United Kingdom. The study cohort were CYP born between 1988
      and 2004 who were newly diagnosed with epilepsy and identified using a nationally
      representative primary care database from the United Kingdom. Reference unit
      costs were applied to each element of HRU to calculate annual direct medical
      costs per child. We assessed whether HRU and costs differed by time from
      diagnosis, age, sex and socioeconomic deprivation. Of 798 CYP newly diagnosed
      with epilepsy, 56% were male and the mean age at diagnosis was 5.6 years. The
      highest burden of HRU was in the first year following diagnosis with a mean
      annual cost of L930 (95% confidence interval (CI) L839-1022) per child in this
      first year. This decreased to L461 (95%CI 368-551) in the second year which
      remained fairly constant each subsequent year (L413 (95% CI 282-540) in the 8th
      year). The highest contribution to the annual medical costs was from inpatient
      hospital admissions followed by the costs of AEDs. Mean annual medical costs were
      significantly higher in children under 6 years of age compared with older
      children (p<0.01), but were similar across socioeconomic groups (p=0.62). The
      direct medical costs of HRU in CYP with epilepsy are higher in the first year
      after diagnosis compared to subsequent years, reflecting HRU related to the
      diagnostic process in the first year. Medical costs did not vary substantially by
      sex or socioeconomic deprivation indicating a similar level of consultation and
      care across these groups. 

PMID- 24447612
TI  - Lack of antibodies to NMDAR or VGKC-complex in GAD and cardiolipin antibody
      positive refractory epilepsy.
AB  - BACKGROUND: Over the last few years autoantibodies against neuronal proteins have
      been identified in several forms of autoimmune encephalitis and epilepsy. NMDA
      receptor (NMDAR) and voltage gated potassium channel (VGKC) complex antibodies
      are mainly associated with limbic encephalitis (LE) whereas glutamic acid
      decarboxylase antibodies (GADA) and anticardiolipin (ACL) antibodies are more
      commonly detected in patients with chronic epilepsy. Clinical features vary
      between these antibodies suggesting the specificity of different neuronal
      antibodies in seizures. METHODS: Serum samples of 14 GADA positive and 24 ACL
      positive patients with refractory epilepsy were analyzed for the presence of VGKC
      or NMDAR antibodies. RESULTS: No positive VGKC or NMDAR antibodies were found in
      these patients. CONCLUSIONS: The results confirm the different significance of
      these neuronal antibodies in seizure disorders. Different autoantibodies have
      different significance in seizures and probably have different pathophysiological
      mechanisms of actions.

PMID- 24447613
TI  - Perinatal common mental disorders among women and the social and emotional
      development of their infants in rural Vietnam.
AB  - BACKGROUND: Little is known about the effect of common mental disorders (CMD)
      among women in the perinatal period on infant development in low-income
      countries. The aim of this study was to examine the effect of exposures to
      maternal symptoms of ante- and post-natal CMD on infant social-emotional
      development in a low-income setting. METHODS: A prospective community-based
      investigation in which a cohort of pregnant women was recruited in rural northern
      Vietnam and followed until 6 months postpartum. Psychosocial and biological data
      were collected in four assessment waves. The outcome was 6-month old infants'
      scores on the Bayley Scales of Infant and Toddler Development Social-Emotional
      Questionnaire. Direct and indirect effects of maternal CMD on the outcome were
      tested simultaneously with path analysis. RESULTS: Complete data were available
      for 378 mother-infant dyads. There were no direct effects of ante- or post-natal
      CMD on infant Social-Emotional scores. However, there was an indirect pathway
      (path coefficient -1.11, 95% CI -1.79 to -0.42) in which antenatal CMD were
      associated with increased likelihood of postnatal CMD, which were associated with
      reduced parenting self-efficacy and less affectionate and warm parenting
      practices, which were associated with lower infant social-emotional scores.
      Parenting self-efficacy and practices also mediated the adverse effects of a
      woman being young or of high parity or experiencing poverty, intimate partner
      violence, a poor relationship with her own mother, non-economic life adversity
      and insufficient breastmilk, on infant social-emotional development. LIMITATIONS:
      We acknowledge some limitations including (1) a moderate rate of attrition, (2)
      the use of a screening test for perinatal CMD, (3) the Bayley scales are not yet
      validated for use in Vietnam and (4) possible response bias in which maternal
      perceptions of their infants were influenced by their mood. CONCLUSIONS: These
      data indicate that women's antenatal and postnatal mental health is a crucial but
      currently inadequately understood determinant of the social and emotional
      development of infants in low-income settings.

PMID- 24447614
TI  - Ultrasound backscatter microscopy image-guided intraventricular gene delivery at
      murine embryonic age 9.5 and 10.5 produces distinct transgene expression patterns
      at the adult stage.
AB  - In utero injection of a retroviral vector into the embryonic telencephalon aided
      by ultrasound backscatter microscopy permits introduction of a gene of interest
      at an early stage of development. In this study, we compared the tissue
      distribution of gene expression in adult mice injected with retroviral vectors at
      different embryonic ages in utero. Following ultrasound image-guided gene
      delivery (UIGD) into the embryonic telencephalon, adult mice were subjected to
      whole-body luciferase imaging and immunohistochemical analysis at 6 weeks and 1
      year postinjection. Luciferase activity was observed in a wide range of tissues
      in animals injected at embryonic age 9.5 (E9.5), whereas animals injected at
      E10.5 showed brain-localized reporter gene expression. These results suggest that
      mouse embryonic brain creates a closed and impermeable structure around E10.
      Therefore, by injecting a transgene before or after E10, transgene expression can
      be manipulated to be local or systemic. Our results also provide information that
      widens the applicability of UIGD beyond neuroscience studies.

PMID- 24447615
TI  - Simultaneous viewing of individual cells and ambient microvasculature using
      optical absorption and fluorescence contrasts.
AB  - Viewing individual cells and ambient microvasculature simultaneously is crucial
      for understanding tumor angiogenesis and microenvironments. We developed a
      confocal fluorescence microscopy (CFM) and photoacoustic microscopy (PAM) dual
      modality imaging system that can assess fluorescent contrast and optical
      absorption contrast in biologic samples simultaneously. After staining tissues
      with fluorescent dye at an appropriate concentration, each laser pulse can
      generate not only sufficient fluorescent signals from cells for CFM but also
      sufficient photoacoustic signals from microvessels for PAM. To explore the
      potential of this system for diagnosis of bladder cancer, experiments were
      conducted on a rat bladder model. The CFM image depicts the morphology of
      individual cells, showing not only large polygonal umbrella cells but also
      intracellular components. The PAM image acquired at the same time provides
      complementary information on the microvascular distribution in the bladder wall,
      ranging from large vessels to capillaries. This device provides an opportunity to
      realize both histologic assay and microvascular characterization simultaneously.
      The combination of the information of individual cells and local microvasculature
      in the bladder offers the capability of envisioning the viability and activeness
      of these cells and holds promise for more comprehensive study of bladder cancer
      in vivo.

PMID- 24447616
TI  - Screening of a novel peptide targeting the proteoglycan-like region of human
      carbonic anhydrase IX.
AB  - The extracellular domain of human carbonic anhydrase IX (CA IX) is extended by a
      proteoglycan-like region (PGLR). The aim of the present study was the development
      of novel molecules with specificity for PGLR, which may be used for tumor
      targeting and imaging. PGLR was chemically synthesized, and phage display
      biopanning was performed. The identified ligand PGLR-P1 was labeled with 125I and
      characterized for target binding and metabolic stability. In vitro
      characterization included kinetic, competition, and internalization studies on CA
      IX-positive renal cell carcinoma SKRC 52 cells. The CA IX-negative cell lines
      HEK293 wt and BxPC3 were used as negative controls. In vitro binding experiments
      revealed an increasing affinity of 125I-PGLR-P1 to SKRC 52 cells but not to
      negative control HEK293 wt and BxPC3 cells. Internalization studies indicated an
      exclusive cell membrane binding. Biodistribution analysis demonstrated a higher
      accumulation in SKRC 52 tumors than in most normal tissues after perfusion. In
      vivo blocking led to a significant decrease in tumor uptake. Our findings
      indicate that PGLR-P1 is a promising lead structure for the development of new
      peptide-based ligands targeting the PGLR of CA IX and reveal challenges that need
      to be considered for peptide-related molecular imaging.

PMID- 24447617
TI  - The simplified reference tissue model with 18F-fallypride positron emission
      tomography: choice of reference region.
AB  - The development of high-affinity radiotracers for positron emission tomography
      (PET) has allowed for quantification of dopamine receptors in extrastriatal and
      striatal regions of the brain. As these new radiotracers have distinctly
      different kinetic properties than their predecessors, it is important to examine
      the suitability of kinetic models to represent their uptake, distribution, and in
      vivo washout. Using the simplified reference tissue model, we investigated the
      influence of reference region choice on the striatal binding potential of 18F
      fallypride, a high-affinity dopamine D2/D3 receptor ligand. We compared the use
      of the visual cortex and a white matter region (superior longitudinal fasciculus)
      to the cerebellum, a commonly used reference tissue, in a PET-fallypride study of
      healthy and methamphetamine-dependent subjects. Compared to the cerebellum, use
      of the visual cortex produced significantly greater sample variance in binding
      potential relative to nondisplaceable uptake (BP(ND)). Use of the white matter
      region was associated with BP(ND) values and sample variance similar to those
      obtained with the cerebellum and a larger effect size for the group differences
      in striatal BP(ND) between healthy and methamphetamine-dependent subjects. Our
      results do not support the use of the visual cortex as a reference region in 18F
      fallypride studies and suggest that white matter may be a reasonable alternative
      to the cerebellum as it displays similar statistical and kinetic properties.

PMID- 24447618
TI  - In vivo imaging of brain aromatase in female baboons: [11C]vorozole kinetics and
      effect of the menstrual cycle.
AB  - The aim of this work was to quantify the brain distribution of the enzyme
      aromatase in the female baboon with positron emission tomography and the tracer
      [11C]vorozole using three different quantification methods for estimating the
      total distribution volume (V(T)): a graphical method, compartment modeling, and a
      tissue to plasma ratio. The graphical model and the compartment modeling gave
      similar estimates to the data and similar values (correlation R  =  .988; p  = 
      .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively
      constant accumulation, suggesting the possibility of using the tissue to plasma
      ratio as an estimate of V(T). The highest uptake of [11C]vorozole in the baboon
      brain was measured in the amygdala, followed by the preoptic area and
      hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with
      vorozole or letrozole showed a generalized decrease in brain accumulation and
      V(T). The results suggested that the physiologic changes in gonadal hormone
      levels accompanying the menstrual cycle had a significant effect on brain
      aromatase V(T).

PMID- 24447619
TI  - Imaging of CD47 expression in xenograft and allograft tumor models.
AB  - CD47 functions as a marker of "self" by inhibiting phagocytosis of autologous
      cells. CD47 has been shown to be overexpressed by various tumor types as a means
      of escaping the antitumor immune response. The goal of this research was to
      investigate the utility of CD47 imaging using positron emission tomography (PET)
      in both human xenograft and murine allograft tumor models. Anti-CD47 antibodies
      were conjugated with p-isothiocyanatobenzyldesferrioxamine (Df-Bz-NCS) and
      labeled with 89Zr. We employed xenograft and allograft small-animal models of
      cancer in biodistribution and PET imaging studies to investigate the specificity
      and PET imaging robustness of CD47. Ab-Df-Bz-NCS conjugates were labeled with
      89Zr with specific activity of 0.9 to 1.6 MUCi/MUg. Biodistribution studies in
      the xenograft and allograft model showed similar specific tumor uptake of the
      antihuman and antimouse CD47 antibodies. However, the tracer retention in the
      liver, spleen, and kidneys was significantly higher in the allograft-bearing
      animals, suggesting uptake mediated by the CD47 normally expressed throughout the
      reticular endothelial system. CD47, a marker of "self," was evaluated as a
      diagnostic PET biomarker in xenograft and allograft cancer animal models. CD47
      imaging is feasible, warranting further studies and immunoPET tracer development.

PMID- 24447621
TI  - Evidence for instant blood-mediated inflammatory reaction in clinical autologous
      islet transplantation.
AB  - A nonspecific inflammatory and thrombotic reaction termed instant blood-mediated
      inflammatory reaction (IBMIR) has been reported when allogenic or xenogenic
      islets come into contact with blood. This reaction is known to cause significant
      loss of transplanted islets. We hypothesized that IBMIR occurs in patients
      undergoing total pancreatectomy followed by autologous islet transplantation (TP
      AIT) and tested this hypothesis in 24 patients and in an in vitro model. Blood
      samples drawn during the peritransplant period showed a significant and rapid
      increase of thrombin-anti-thrombin III complex (TAT) and C-peptide during islet
      infusion, which persisted for up to 3 h, along with a decreased platelet count. A
      concomitant increase in levels of inflammatory proteins IL-6, IL-8 and interferon
      inducible protein-10 was observed. An in vitro model composed of pure islets plus
      autologous blood also demonstrated significantly increased levels of TAT
      (p<0.05), C-peptide (p<0.05), tumor necrosis factor-alpha (p<0.05) and MCP-1
      (p<0.05), as well as strong tissue factor expression in islets. Islet viability
      decreased significantly but was rescued by the presence of low-molecular-weight
      dextran sulfate. In conclusion, AIT-induced elevation of TAT and destruction of
      islets suggests that IBMIR might occur during AIT. Modulating this process may
      help improve islet engraftment and the insulin independence rate in TP-AIT
      patients.

PMID- 24447620
TI  - A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: To assess the efficacy and safety of olesoxime, a
      molecule with neuroprotective properties, in patients with amyotrophic lateral
      sclerosis (ALS) treated with riluzole. METHODS: A double-blind, randomized,
      placebo-controlled, multicenter trial of 18 months' duration was conducted in 512
      subjects, with probable or definite ALS and a slow vital capacity (SVC) >=70%,
      receiving 330 mg olesoxime daily or matching placebo and 50 mg riluzole twice a
      day in all. The primary intention-to-treat (ITT) outcome analysis was 18 months'
      survival. Secondary outcomes were rates of deterioration of the revised ALS
      functional rating scale (ALSFRS-R), focusing on the 9-month assessment, SVC and
      manual muscle testing. Blood levels, safety and tolerability of olesoxime were
      also assessed. RESULTS: At 18 months, 154 of the 512 ITT patients had died (79 of
      253 placebo, 75 of 259 olesoxime). Estimated overall survival according to Kaplan
      Meier analysis was 67.5% (95% CI 61.0%-73.1%) in the placebo group and 69.4% (95%
      CI 63.0%-74.9%) in the olesoxime group; hence survival was not significantly
      different between treatment arms (P = 0.71, stratified bulbar/spinal log-rank).
      The other efficacy end-points evaluated were also negative, with the exception of
      a small difference in ALSFRS-R global score at 9 months in favor of olesoxime but
      not sustained after 18 months' treatment nor evident in either the stratified
      bulbar or spinal subpopulations. Treatment did not raise any safety concerns.
      CONCLUSIONS: Olesoxime, although well tolerated, did not show a significant
      beneficial effect in ALS patients treated with riluzole.

PMID- 24447622
TI  - Recurrence of animal rabies, Greece, 2012.

PMID- 24447623
TI  - Patterns of condom use by men who have sex with men before and after the Avahan
      intervention in Andhra Pradesh state of India.
AB  - BACKGROUND: Two rounds of integrated biological and behavioural assessment (IBBA)
      surveys were done among men who have sex with men (MSM) in Andhra Pradesh during
      2006 and 2009. Avahan, the India AIDS initiative, funded by the Bill and Melinda
      Gates Foundation implemented HIV prevention interventions among MSM starting
      around the time of the first round of IBBA. METHODS: Data on socio-demographic,
      sex behaviour characteristics and HIV status of MSM from the two IBBA rounds were
      used. Changes in the rates of consistent condom use over the past one month by
      MSM with various types of partners between the two rounds were assessed.
      Multivariate analysis was performed to assess associations between various
      factors and inconsistent condom use for sex with regular partners as well as HIV
      in MSM. RESULTS: A significant increase in consistent condom use by MSM was noted
      from 2006 to 2009 for paid male partners (19.5% to 93.8%), occasional male
      partners (13.2% to 86.2%), and paid female partners (25.9% to 94.2%). Consistent
      condom use with regular sex partners also increased but remained lower with
      regular male partner (75.8%) and very low with regular female partners (15.7%).
      MSM who used condoms inconsistently with their regular male partner were also
      more likely to use condoms inconsistently with their regular female partner.
      Multivariate analysis showed MSM who used condoms inconsistently with regular
      male partner had higher odds of HIV (odds ratio 1.8; 95% CI 1.2-2.7). MSM who
      received condoms from Avahan had the lowest odds (odds ratio 0.3; 95% CI 0.1-0.5)
      of inconsistent condom use with regular male partners. CONCLUSIONS: Condom use by
      MSM increased markedly after implementation of Avahan, though a causal
      association cannot be assessed with the available data. The relatively lower
      condom use with regular partners of MSM suggests that additional programme effort
      is needed to address this aspect specifically.

PMID- 24447624
TI  - Angiotensin AT2 receptors and the baroreflex control of renal sympathetic nerve
      activity.

PMID- 24447625
TI  - Treatment of complex perianal fistulas with seton and infliximab in adolescents
      with Crohn's disease.
AB  - BACKGROUND AND AIMS: Treatment of complex perianal fistulas associated with
      Crohn's disease is challenging. In adults, seton drainage combined with
      infliximab therapy has proven to be more effective than either one alone. Results
      following such treatment among pediatric patients have not been reported
      previously. The aim of this study was to describe outcomes after combined seton
      and infliximab treatment for complex perianal fistulas in adolescents with
      Crohn's disease. METHODS: We performed a retrospective medical record review of
      all consecutive Crohn's disease patients treated for perianal fistulas with seton
      drainage and infliximab between 2007 and 2013 (n=13). A follow-up interview was
      conducted at median of two years. RESULTS: Median age at fistula diagnosis was
      14years. Following seton placement in fistula tracks, infliximab induction was
      administered at weeks 0, 2, and 6 and maintenance therapy at 8-week intervals.
      Over 90% responded to seton drainage and infliximab induction. Final fistula
      response was obtained at median of 8weeks, being complete in 77% and partial in
      15%. Setons were kept in place for median of 8months. Fistulas recurred in 23%
      over a year after the final response. At last follow-up, 85% still had a response
      and 70% were free from perianal symptoms. Most were still on anti-TNF-alpha
      therapy, but one third had switched to adalimumab. Patients' anorectal function
      was well preserved and overall satisfaction with the treatment was high.
      CONCLUSIONS: The results suggest that combining seton drainage with infliximab
      therapy improves the perianal fistula response rates in pediatric patients.

PMID- 24447626
TI  - The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin as a novel allergic rhinitis
      control agent.
AB  - AIMS: The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary
      metabolite extracted from Corydalis heterocarpa, which has long been used as a
      folk medicine for various inflammatory diseases in Korea. We examined the effect
      of OMC on allergic rhinitis (AR). MAIN METHODS: We assessed the therapeutic
      effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate
      plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR
      models. KEY FINDINGS: OMC significantly decreased the releases of histamine and
      tryptase from stimulated HMC-1 cells. The degranulation process, characterized by
      morphological extension of the filopodia on the surface and membrane ruffling,
      was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the
      morphological changes in stimulated-HMC-1 cells. OMC reduced the production and
      mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were
      dependent on the regulation of mitogen-activated protein kinases, nuclear factor
      kappaB, and caspapase-1 signaling pathways. In the AR animal model, the increased
      rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized
      mice were significantly reduced by the administration of OMC. Furthermore,
      eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked
      through the regulation of macrophage-inflammatory protein and intercellular
      adhesion molecule-1 levels. SIGNIFICANCE: OMC showed the possibility to regulate
      AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC
      is a powerful and feasible new agent to suppress AR.

PMID- 24447628
TI  - Dobutamine mediates cytoprotection by induction of heat shock protein 70 in
      vitro.
AB  - AIMS: Dobutamine is cytoprotective when applied before a subsequent stress.
      However, the underlying molecular mechanism is unknown. Dobutamine also inhibits
      nuclear factor (NF)-kappaB in human T lymphocytes. Other inhibitors of NF-kappaB
      induce a so-called heat shock response. We hypothesized that dobutamine mediates
      protection from apoptotic cell death by the induction of a heat shock response.
      MAIN METHODS: Jurkat T lymphoma cells were preincubated with dobutamine (0.1, 0.5
      mM) before the induction of apoptosis (staurosporine, 2 MUM). DNA-binding of heat
      shock factor (HSF)-1 was analyzed by electrophoretic mobility shift assay, mRNA
      expression of heat shock protein (hsp)70 and hsp90 by Northern Blot, activity of
      caspase-3 by fluorogenic caspase activity assay and cleavage of pro-caspase-3 by
      Western Blot. Apoptosis was assessed by flow cytometry after annexin V
      fluorescein isothiocyanate staining. Hsp70 and hsp90 were inhibited using N
      formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam and 17-allylamino-17
      demethoxygeldana-mycin, respectively. All data are given as median and 25/75%
      percentile. KEY FINDINGS: Pre-incubation with dobutamine inhibited staurosporine
      induced annexin V-fluorescence (28 [20-32] % vs. 12 [9-15] % for dobutamine 0.1
      mM and 7 [5-12] % for dobutamine 0.5 mM, p<0.001), cleavage of pro-caspase-3 as
      well as caspase-3-like activity (0.46 [0.40-0.48] vs. 0.32 [0.27-0.39] for
      Dobutamine 0.1 mM and 0.20 [0.19-0.23] for Dobutamine 0.5 mM, p<0.01). Dobutamine
      induced DNA-binding of HSF-1 and mRNA-expression of hsp70 and hsp90. While
      inhibition of Hsp90 had no effect, inhibition of Hsp70 increased the number of
      annexin V-positive cells (33 [32-36] % vs. 18 [16-24] %) and caspase-3-like
      activity (0.21 [0.19-0.23] vs. 0.16 [0.13-0.17], p<0.05). SIGNIFICANCE:
      Dobutamine protects from apoptotic cell death via the induction of Hsp70.

PMID- 24447627
TI  - Alpha1 catalytic subunit of AMPK modulates contractile function of cardiomyocytes
      through phosphorylation of troponin I.
AB  - AIMS: The specific role of AMPKalpha1 or AMPKalpha2 in mediating cardiomyocyte
      contractile function remains elusive. The present study investigated how AMPK
      activation modulates the contractility of isolated cardiomyocytes. MAIN METHODS:
      Mechanical properties and intracellular Ca(2+) properties were measured in
      isolated cardiomyocytes. The stress signaling was evaluated using western blot
      and immunoprecipitation analysis. KEY FINDINGS: AMPK activator, A-769662 induced
      maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt), peak height
      and peak shortening (PS) amplitude in both WT and AMPKalpha2 KO cardiomyocytes,
      but did not affect time-to-90% relengthening (TR90). AMPK KD cardiomyocytes
      demonstrated contractile dysfunction compared with cardiomyocytes from WT and
      AMPKalpha2 KO hearts. However, the rise of intracellular Ca(2+) levels as well as
      intracellular ATP levels has no significant difference among WT, AMPKalpha2 KO
      and AMPK KD groups with and without the presence of A-769662. Besides, WT,
      AMPKalpha2 KO and AMPK KD group displayed a phosphorylated AMPK and downstream
      acetyl-CoA carboxylase (ACC) phosphorylation. Interestingly, A-769662 also
      triggered troponin I (cTnI) phosphorylation at Ser(149) site which is related to
      contractility of cardiomyocytes. Furthermore, the immunoprecipitation analysis
      revealed that AMPKalpha1 of cardiomyocytes was phosphorylated by A-769662.
      SIGNIFICANCE: This is the first study illustrating that activation of AMPK plays
      a significant role in mediating the contractile function of cardiomyocytes using
      transgenic animal models. AMPK activator facilitates the contractility of
      cardiomyocytes via activating AMPKalpha1 catalytic subunit. The phosphorylation
      of cTnI by AMPK could be a factor attributing to the regulation of contractility
      of cardiomyocytes.

PMID- 24447629
TI  - Effects of two lipid lowering therapies on immune responses in hyperlipidemic
      subjects.
AB  - AIMS: To compare the effects of two of the most effective lipid-lowering
      therapies with similar LDL-cholesterol reduction capacity on the innate and
      adaptive immune responses through the evaluation of autoantibodies anti-oxidized
      LDL (anti-oxLDL Abs) and electronegative LDL [LDL(-)] levels. MAIN METHODS: We
      performed a prospective, randomized, open label study, with parallel arms and
      blinded endpoints. One hundred and twelve subjects completed the study protocol
      and received rosuvastatin 40 mg or ezetimibe/simvastatin 10/40 mg for 12 weeks.
      Lipids, apolipoproteins, LDL(-), and anti-oxLDL Abs (IgG) were assayed at
      baseline and end of study. KEY FINDINGS: Main clinical and laboratory
      characteristics were comparable at baseline. Lipid modifications were similar in
      both treatment arms, however, a significant raise in anti-oxLDL Abs levels was
      observed in subjects treated with rosuvastatin (p=0.026 vs. baseline), but not in
      those receiving simvastatin/ezetimibe. (p=0.233 vs. baseline), thus suggesting
      modulation of adaptive immunity by a potent statin. Titers of LDL(-) were not
      modified by the treatments. SIGNIFICANCE: Considering atherosclerosis as an
      immune disease, this study adds new information, showing that under similar LDL
      cholesterol reduction, the choice of lipid-lowering therapy can differently
      modulate adaptive immune responses.

PMID- 24447631
TI  - Serum big endothelin-1 as a clinical marker for cardiopulmonary and neoplastic
      diseases in dogs.
AB  - AIMS: Many studies of human subjects have demonstrated the utility of assessing
      serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in
      cardiopulmonary and neoplastic diseases. In this study we explored the
      feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with
      various cardiopulmonary and neoplastic diseases. MAIN METHODS: Serum big ET-1
      levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic
      diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two
      groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured
      by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the
      dogs with the diseases were compared with levels in normal healthy dogs (n=17).
      KEY FINDINGS: Dogs with cardiopulmonary disease (4.6+/-4.6 pmol/l) showed a
      significantly (P<0.01) higher level of big ET-1 than healthy control dogs (1.1+/
      0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2+/-5.3
      pmol/l) were significantly (P<0.01) higher than those without pulmonary
      hypertension (2.0+/-0.6 pmol/l). Dogs with hemangiosarcoma (5.6+/-2.2 pmol/l),
      adenocarcinoma (2.0+/-1.8 pmol/l), histiocytic sarcoma (3.3+/-1.9 pmol/l),
      chondrosarcoma or osteosarcoma (3.0+/-1.6 pmol/l) and hepatocellular carcinoma
      (2.7+/-1.8 pmol/l) showed significantly (P<0.05) higher levels than healthy
      control dogs. SIGNIFICANCE: These findings point to the potential of serum big ET
      1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs.

PMID- 24447630
TI  - Dual endothelin receptor antagonism with bosentan reverses established vascular
      remodeling and dysfunctional angiogenesis in diabetic rats: relevance to glycemic
      control.
AB  - AIMS: We have shown that diabetes causes cerebrovascular remodeling in part by
      the activation of the endothelin (ET-1) system in a glucose-dependent manner. We
      also reported increased yet dysfunctional cerebral angiogenesis in diabetes.
      Here, we tested the hypothesis that dual ET-1 receptor antagonism or glycemic
      control can reverse already established diabetes-induced vascular remodeling and
      neovascularization. MAIN METHODS: 18-week non-obese type-2 diabetic Goto-Kakizaki
      (GK) were treated with vehicle, metformin (300 mg/kg/day) or bosentan (100
      mg/kg/day) for 4 weeks by oral gavage and compared to 10 and 18-weeks GK rats.
      Isolated middle cerebral artery (MCA) lumen diameter (LD), media thickness (MT),
      media:lumen (M:L) ratio, and cross-sectional area (CSA) were measured using
      pressurized arteriograph. Assessment of remodeling and angiogenesis in the brain
      parenchyma was achieved by three-dimensional reconstruction of fluorescently
      labeled images of the vasculature acquired by confocal microscopy, and
      measurement of neovascularization indices including vascular volume and surface
      area, branch density and tortuosity. KEY FINDINGS: MCA remodeling (increased M:L
      ratio and CSA, but decreased LD) occurred by 18 weeks and did not progress by 22
      weeks in diabetic GK rats. Metformin and bosentan partially corrected large
      artery remodeling. Both treatments significantly reduced all indices of
      neovascularization compared to untreated diabetic rats. SIGNIFICANCE: Glycemic
      control or ET-1 antagonism can partially reverse diabetes-induced cerebrovascular
      remodeling and neovascularization. These results strongly suggest that either
      approach offers a therapeutic benefit and combination treatments need to be
      tested.

PMID- 24447632
TI  - Endothelin receptor antagonist exacerbates autoimmune myocarditis in mice.
AB  - AIMS: Myocarditis and subsequent dilated cardiomyopathy are major causes of heart
      failure in young adults. Experimental autoimmune myocarditis (EAM) is a mouse
      model of post-infectious myocarditis and inflammatory cardiomyopathy. The
      pathological role of endothelin (ET) in myocarditis has not been elucidated. MAIN
      METHODS: EAM was induced by immunization of cardiac myosin peptide with complete
      Freund's adjuvant on days 0 and 7 in BALB/c mice. An ETA/ETB dual receptor
      antagonist, SB209670, was administered by a continuous infusion from a
      subcutaneous pump for 2 weeks. KEY FINDINGS: An increase in the heart-to-body
      weight ratio was observed in SB209670-treated mice compared with vehicle-treated
      mice. Heart pathology in SB209670-treated mice was remarkable for gross
      inflammatory infiltration, in contrast to the lesser inflammation in the hearts
      of vehicle-treated mice. We found that an ET blockade decreased the number of
      Foxp3(+) regulatory T cells in the heart. The ET blockade also inhibited the
      expression of the suppressor of cytokine signaling 3 that plays a key role in the
      negative regulation of both Toll-like receptor- and cytokine receptor-mediated
      signaling. EAM is a CD4(+) T cell-mediated disease. CD4(+) T cells isolated from
      SB209670-treated EAM mice produced less IL-10 and more inflammatory cytokines, IL
      6 and IL-17, than those isolated from vehicle-treated mice. SIGNIFICANCE: The ET
      receptor antagonist exacerbated autoimmune myocarditis in mice. Our novel
      findings suggest that ET may play an important role in the regulation of
      inflammation in myocarditis.

PMID- 24447634
TI  - Organic and metal contamination in marine surface sediments of Guanica Bay,
      Puerto Rico.
AB  - Land based sources of pollution have the potential to adversely impact valuable
      coral reef ecosystems. In Guanica Bay (Puerto Rico) sediment samples collected
      and analyzed in 2009 demonstrate unusually high concentrations of total
      chlordane, total PCBs, nickel and chromium. A variety of other contaminants
      (total DDT, total PAHs, As, Cu, Hg, and Zn) were also at levels which may
      indicate sediment toxicity. With the exception of chromium, all of these
      contaminants were detected in coral tissues (Porites astreoides), although it is
      unclear at what level these contaminants affect coral health. PCBs and chlordane
      are environmentally persistent and likely represent legacy pollution from
      historical uses in close geographic proximity to the Bay. We hypothesize that the
      high nickel and chromium levels are due to a combination of naturally high Ni and
      Cr in rock and soils in the watershed, and enhanced (human driven) erosional
      rates. 

PMID- 24447633
TI  - A critical analysis of test-retest reliability in instrument validation studies
      of cancer patients under palliative care: a systematic review.
AB  - BACKGROUND: Patient-reported outcome validation needs to achieve validity and
      reliability standards. Among reliability analysis parameters, test-retest
      reliability is an important psychometric property. Retested patients must be in a
      clinically stable condition. This is particularly problematic in palliative care
      (PC) settings because advanced cancer patients are prone to a faster rate of
      clinical deterioration. The aim of this study was to evaluate the methods by
      which multi-symptom and health-related qualities of life (HRQoL) based on patient
      reported outcomes (PROs) have been validated in oncological PC settings with
      regards to test-retest reliability. METHODS: A systematic search of PubMed (1966
      to June 2013), EMBASE (1980 to June 2013), PsychInfo (1806 to June 2013), CINAHL
      (1980 to June 2013), and SCIELO (1998 to June 2013), and specific PRO databases
      was performed. Studies were included if they described a set of validation
      studies. Studies were included if they described a set of validation studies for
      an instrument developed to measure multi-symptom or multidimensional HRQoL in
      advanced cancer patients under PC. The COSMIN checklist was used to rate the
      methodological quality of the study designs. RESULTS: We identified 89 validation
      studies from 746 potentially relevant articles. From those 89 articles, 31
      measured test-retest reliability and were included in this review. Upon critical
      analysis of the overall quality of the criteria used to determine the test-retest
      reliability, 6 (19.4%), 17 (54.8%), and 8 (25.8%) of these articles were rated as
      good, fair, or poor, respectively, and no article was classified as excellent.
      Multi-symptom instruments were retested over a shortened interval when compared
      to the HRQoL instruments (median values 24 hours and 168 hours, respectively; p =
      0.001). Validation studies that included objective confirmation of clinical
      stability in their design yielded better results for the test-retest analysis
      with regard to both pain and global HRQoL scores (p < 0.05). The quality of the
      statistical analysis and its description were of great concern. CONCLUSION: Test
      retest reliability has been infrequently and poorly evaluated. The confirmation
      of clinical stability was an important factor in our analysis, and we suggest
      that special attention be focused on clinical stability when designing a PRO
      validation study that includes advanced cancer patients under PC.

PMID- 24447635
TI  - Influence of tuna penning activities on soft bottom macrobenthic assemblages.
AB  - The influence of tuna penning on soft bottom habitat present in the vicinity of
      tuna pens and at distances 200 m and 1.5 km away, was assessed by comparing
      attributes of macroinvertebrate assemblages and sediment quality before (November
      2000, March 2001) and after (November 2001, April 2002) initiation of the
      activity. Results from November 2001 indicated a significant increase in sediment
      organic carbon and organic nitrogen, and a non-significant increase in the
      abundance of Capitellidae in the vicinity of the cages. Similar results were
      obtained 200 m from the cages but not 1.5 km away, where the only change was a
      significant increase in organic nitrogen in sediment. Results from April 2002
      indicated no significant change in sediment organic carbon and organic nitrogen,
      however, mean sediment grain size decreased significantly in the immediate
      vicinity of the cages. Changes in attributes of the benthic assemblages and
      sediment resulted from accumulation of uneaten feed-fish on the seabed.

PMID- 24447636
TI  - Puerarin blocks the signaling transmission mediated by P2X3 in SG and DRG to
      relieve myocardial ischemic damage.
AB  - P2X3 receptors in stellate ganglia (SG) and cervical dorsal root ganglia (DRG)
      neurons are involved in sympathoexcitatory reflex induced by myocardial ischemic
      damage. Puerarin, a major active ingredient extracted from the traditional
      Chinese plant medicine Ge-gen, has been widely used in treatment of myocardial
      and cerebral ischemia. The present study is aimed to observe the effects of
      puerarin on the signaling transmission mediated by P2X3 receptor in SG and DRG
      after myocardial ischemic damage. Our results showed that systolic blood pressure
      and heart rate increased, and the expression levels of P2X3 mRNA and protein in
      SG and DRG were up-regulated after myocardial ischemic damage. Puerarin reduced
      systolic blood pressure and heart rate, relieved pain and decreased up-regulated
      expression of P2X3 mRNA and protein in SG and DRG after myocardial ischemia.
      Puerarin inhibited the up-regulated ATP-activated currents in DRG neurons after
      myocardial ischemia. Thus, puerarin can relieve myocardial ischemic damage
      through blocking the P2X3 signaling transmission and then depressed the
      aggravated sympathoexcitatory reflex.

PMID- 24447637
TI  - Variation in performance of candidate surgical quality measures for muscle
      invasive bladder cancer by hospital type.
AB  - OBJECTIVE: To test the association between hospital type and performance of
      candidate quality measures for treatment of muscle-invasive bladder cancer (MIBC)
      using a large national tumour registry. Proposed quality measures include receipt
      of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection,
      and continent urinary diversion. PATIENTS AND METHODS: Using the National Cancer
      Database, patients with stage >=II urothelial carcinoma treated with radical
      cystectomy (RC) from 2003 to 2010 were identified. Hospitals were grouped by type
      and annual RC volume: community, comprehensive low volume (CLV), comprehensive
      high volume (CHV), academic low volume (ALV), and academic high volume (AHV)
      groups. Logistic regression models were used to test the association between
      hospital group and performance of quality measures, adjusting for year,
      demographic, and clinical/pathological characteristics; generalised estimating
      equations were fitted to the models to adjust for clustering at the hospital
      level. RESULTS: In all, 23 279 patients underwent RC at community (12.4%),
      comprehensive (CLV 38%, CHV 5%), and academic (ALV 17%, AHV 28%) hospitals. While
      only 0.8% (175) of patients met all four quality criteria, 61% of patients
      treated at AHV hospitals met two or more quality metric indicators compared with
      ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals (P < 0.001). After
      adjustment, patients were more likely to receive two or more quality measures
      when treated at AHV (odds ratio [OR] 2.4, confidence interval [CI] 2.0-2.9), ALV
      (OR 1.3, CI 1.1-1.6), and CHV (OR 1.3, CI 1.03-1.7) hospitals compared with
      community hospitals. CONCLUSIONS: Patients undergoing RC at AHV hospitals were
      more likely to meet quality criteria. However, performance remains low across
      hospital types, highlighting the opportunity to improve quality of care for MIBC.

PMID- 24447638
TI  - Assembling a geospatial database of tsetse-transmitted animal trypanosomosis for
      Africa.
AB  - BACKGROUND: African animal trypanosomosis (AAT), or nagana, is widespread within
      the tsetse-infested belt of sub-Saharan Africa. Although a wealth of information
      on its occurrence and prevalence is available in the literature, synthesized and
      harmonized data at the regional and continental scales are lacking. To fill this
      gap the Food and Agriculture Organization of the United Nations (FAO) launched
      the Atlas of tsetse and AAT, jointly implemented with the International Atomic
      Energy Agency (IAEA) in the framework of the Programme Against African
      Trypanosomosis (PAAT). METHODS: The Atlas aims to build and regularly update a
      geospatial database of tsetse species occurrence and AAT at the continental
      level. The present paper focuses on the methodology to assemble a dynamic
      database of AAT, which hinges on herd-level prevalence data as estimated using
      various diagnostic techniques. A range of ancillary information items is also
      included (e.g. trypanosome species, survey period, species and breed of animals,
      husbandry system, etc.). Input data were initially identified through a
      literature review. RESULTS: Preliminary results are presented for Ethiopia, Kenya
      and Uganda in East Africa: 122 papers were identified and analyzed, which
      contained field data collected from January 1990 to December 2013. Information on
      AAT was extracted and recorded for 348 distinct geographic locations. The
      presented distribution maps exemplify the range of outputs that can be directly
      generated from the AAT database. CONCLUSIONS: Activities are ongoing to map the
      distribution of AAT in all affected countries and to develop the tsetse component
      of the Atlas. The presented methodology is also being transferred to partners in
      affected countries, with a view to developing capacity and strengthening data
      management, harmonization and sharing. In the future, geospatial modelling will
      enable predictions to be made within and beyond the range of AAT field
      observations. This variety of information layers will inform decisions on the
      most appropriate, site-specific strategies for intervention against AAT. Data on
      the occurrence of human-infective trypanosomes in non-human hosts will also
      provide valuable information for sleeping sickness control and elimination.

PMID- 24447639
TI  - Development and characterization of 96 microsatellite markers suitable for QTL
      mapping and accession control in an Arabidopsis core collection.
AB  - BACKGROUND: To identify plant genes involved in various key traits, QTL mapping
      is a powerful approach. This approach is based on the use of mapped molecular
      markers to identify genomic regions controlling quantitative traits followed by a
      fine mapping and eventually positional cloning of candidate genes. Mapping
      technologies using SNP markers are still rather expensive and not feasible in
      every laboratory. In contrast, microsatellite (also called SSR for Simple
      Sequence Repeat) markers are technologically less demanding and less costly for
      any laboratory interested in genetic mapping. RESULTS: In this study, we present
      the development and the characterization of a panel of 96 highly polymorphic SSR
      markers along the Arabidopsis thaliana genome allowing QTL mapping among
      accessions of the Versailles 24 core collection that covers a high percentage of
      the A. thaliana genetic diversity. These markers can be used for any QTL mapping
      analysis involving any of these accessions. We optimized the use of these markers
      in order to reveal polymorphism using standard PCR conditions and agarose gel
      electrophoresis. In addition, we showed that the use of only three of these
      markers allows differentiating all 24 accessions which makes this set of markers
      a powerful tool to control accession identity or any cross between any of these
      accessions. CONCLUSION: The set of SSR markers developed in this study provides a
      simple and efficient tool for any laboratory focusing on QTL mapping in A.
      thaliana and a simple means to control seed stock or crosses between accessions.

PMID- 24447641
TI  - Interplay between intrinsic and acquired resistance to quinolones in
      Stenotrophomonas maltophilia.
AB  - To analyse whether the mutation-driven resistance-acquisition potential of a
      given bacterium might be a function of its intrinsic resistome, quinolones were
      used as selective agents and Stenotrophomonas maltophilia was chosen as a
      bacterial model. S. maltophilia has two elements - SmQnr and SmeDEF - that are
      important in intrinsic resistance to quinolones. Using a battery of mutants in
      which either or both of these elements had been removed, the apparent mutation
      frequency for quinolone resistance and the phenotype of the selected mutants were
      found to be related to the intrinsic resistome and also depended on the
      concentration of the selector. Most mutants had phenotypes compatible with the
      overexpression of multidrug efflux pump(s); SmeDEF overexpression was the most
      common cause of quinolone resistance. Whole genome sequencing showed that
      mutations of the SmeRv regulator, which result in the overexpression of the
      efflux pump SmeVWX, are the cause of quinolone resistance in mutants not
      overexpressing SmeDEF. These results indicate that the development of mutation
      driven antibiotic resistance is highly dependent on the intrinsic resistome,
      which, at least for synthetic antibiotics such as quinolones, did not develop as
      a response to the presence of antibiotics in the natural ecosystems in which S.
      maltophilia evolved. 

PMID- 24447640
TI  - Fungal endophthalmitis associated with compounded products.
AB  - Fungal endophthalmitis is a rare but serious infection. In March 2012, several
      cases of probable and laboratory-confirmed fungal endophthalmitis occurring after
      invasive ocular procedures were reported nationwide. We identified 47 cases in 9
      states: 21 patients had been exposed to the intraocular dye Brilliant Blue G
      (BBG) during retinal surgery, and the other 26 had received an intravitreal
      injection containing triamcinolone acetonide. Both drugs were produced by
      Franck's Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species
      complex mold was identified in specimens from BBG-exposed case-patients and an
      unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from
      triamcinolone-exposed case-patients. Exposure to either product was the only
      factor associated with case status. Of 40 case-patients for whom data were
      available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1
      compounding pharmacy, resulted in a product recall. Ensuring safety and integrity
      of compounded medications is critical for preventing further outbreaks associated
      with compounded products. 

PMID- 24447642
TI  - [Three-dimensional endoscopic endonasal study of skull base anatomy].
AB  - INTRODUCTION: Training in dissection of the paranasal sinuses and the skull base
      is essential for anatomical understanding and correct surgical techniques. Three
      dimensional (3D) visualisation of endoscopic skull base anatomy increases spatial
      orientation and allows depth perception. OBJECTIVE: To show endoscopic skull base
      anatomy based on the 3D technique. METHODS: We performed endoscopic dissection in
      cadaveric specimens fixed with formalin and with the Thiel technique, both
      prepared using intravascular injection of coloured material. Endonasal approaches
      were performed with conventional 2D endoscopes. Then we applied the 3D anaglyph
      technique to illustrate the pictures in 3D. RESULTS: The most important
      anatomical structures and landmarks of the sellar region under endonasal
      endoscopic vision are illustrated in 3D images. CONCLUSION: The skull base
      consists of complex bony and neurovascular structures. Experience with cadaver
      dissection is essential to understand complex anatomy and develop surgical
      skills. A 3D view constitutes a useful tool for understanding skull base anatomy.

PMID- 24447643
TI  - Non-traumatic spontaneous acute epidural hematoma in a patient with sickle cell
      disease.
AB  - A 19-year-old female with sickle cell anemia (SCD) was referred to our hospital
      after two days of hospitalization at another hospital for a headache crisis. This
      headache crisis was due to a raised intracranial pressure; these symptoms were
      noted and included in her comprehensive list of symptoms. There was an acute drop
      in the hemoglobin and hematocrit levels. The cranial CT scan demonstrated a left
      fronto-parietal acute epidural hematoma (AEH) and a calvarial bone expansion,
      which was suggestive of medullary hematopoiesis. The patient underwent emergent
      craniotomy and evacuation of the hematoma. There were no abnormal findings intra
      operatively apart from the AEH, except skull thickening and active petechial
      bleeding from the dural arteries. Repeated CT scan showed a complete evacuation
      of the hematoma. The possible underlying pathophysiological mechanisms were
      discussed. In addition to the factors mentioned in the relevant literature, any
      active petechial bleeding from the dural arteries on the separated surface of the
      dura from the skull could have contributed to the expanding of the AEH in our
      patient. Neurosurgeons and other health care providers should be aware of
      spontaneous AEH in patients with SCD. 

PMID- 24447644
TI  - A survey of software for genome-wide discovery of differential splicing in RNA
      Seq data.
AB  - Alternative splicing is a major contributor to cellular diversity. Therefore the
      identification and quantification of differentially spliced transcripts in genome
      wide transcript analysis is an important consideration. Here, I review the
      software available for analysis of RNA-Seq data for differential splicing and
      discuss intrinsic challenges for differential splicing analyses. Three approaches
      to differential splicing analysis are described, along with their associated
      software implementations, their strengths, limitations, and caveats. Suggestions
      for future work include more extensive experimental validation to assess accuracy
      of the software predictions and consensus formats for outputs that would
      facilitate visualizations, data exchange, and downstream analyses. 

PMID- 24447645
TI  - Increased expression of Dkk1 by HR is associated with alteration of hair cycle in
      hairpoor mice.
AB  - BACKGROUND: Hairless (Hr), a transcriptional corepressor expressed mainly in the
      skin, regulates hair follicle (HF) morphogenesis and hair cycling. Recently, we
      reported a new Hr mutant mouse, "Hairpoor" (Hr(Hp)), that resembles the human
      hair disorder Marie Unna hereditary hypotrichosis (MUHH) in the heterozygous
      state. The Wnt/beta-catenin signaling pathway is critical for homeostasis in
      various adult tissues including skin and HFs. One of the Wnt inhibitors, Dickkopf
      (Dkk), inhibits hair growth during the hair cycle as a catagen inducer of
      apoptosis, resulting in HF reductions. OBJECTIVE: To investigate regulation of
      Dkk1 by HR and its effect on hair formation. METHODS: The relative expression of
      Dkk1 in (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice during the hair cycle was investigated
      using real time PCR and Western blot analysis. Immunohistochemistry was performed
      in order to confirm abnormal expression of Dkk1 in HFs of (+)/Hr(HP) and
      Hr(Hp)/Hr(Hp) mice. To determine whether Dkk1 expression was also regulated by HR
      in vitro, an Hr-transient transfection experiment was performed. Alteration of
      the hair cycle in Hr(HP) heterozygous mice was identified by determination of the
      hair cycle and measurement of HF length. RESULTS: Dkk1 expression was increased
      in the skin of (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice, as well as in Hr-overexpressing
      mouse keratinocytes. Additionally, an earlier entrance of HFs into catagen and
      shortened HF length in (+)/Hr(HP) mice compared to wild-type mice was observed.
      CONCLUSION: Study results suggested that up-regulation of Dkk1 by HR contributed
      to abnormal development of HFs and failure in regeneration of HFs in
      Hr(Hp)/Hr(Hp) mice. These findings also indicated that alteration of the hair
      cycle in (+)/Hr(HP) mice was related to the up-regulation of Dkk1 by HR.

PMID- 24447646
TI  - Photodynamic diagnosis of metastatic lymph nodes using 5-aminolevulinic acid in
      mouse squamous cell carcinoma.

PMID- 24447647
TI  - On the role of sadness in the psychopathology of anorexia nervosa.
AB  - Recent models on the development and maintenance of eating disorders propose
      negative emotions to be important precursors for the occurrence of eating
      disorder symptomatology. In fact, previous research on bulimia nervosa (BN) and
      binge eating disorder provides evidence that negative emotions are an antecedent
      condition for binge eating. However, there is a lack of research examining the
      influence of negative emotions on restrictive eating and exercising in
      individuals with anorexia nervosa (AN). In an experimental study, women with AN
      (n=39) and BN (n=34) as well as a non-eating disordered control group (CG; n=34)
      watched a sadness-inducing film clip. Before and after the film clip participants
      rated their current desire to engage in dietary restriction (DTR) and desire to
      exercise (DTE). Main results reveal that DTR significantly increased after the
      film clip in women with AN only, while DTE decreased over time in all groups.
      Results are in line with the notion that negative emotions have a prominent
      influence on the core eating pathology in AN. 

PMID- 24447648
TI  - D-penicillamine versus zinc sulfate as first-line therapy for Wilson's disease.
AB  - BACKGROUND AND PURPOSE: To compare the course of treatment in patients with
      symptomatic Wilson's disease (WD) receiving either D-penicillamine (DPA) or zinc
      sulfate (ZS) as first-line therapy. METHODS: In all, 143 consecutive patients
      diagnosed with symptomatic WD from January 2005 to December 2009, followed until
      December 2010, were included. The decision about first-line therapy was made
      individually after discussion with the patient. Physicians had no clear
      preference of one drug over the other. Data were analyzed in subgroups with
      predominantly neurological (DPA, 35; ZS, 21) and hepatic (DPA, 36; ZS, 51)
      presentation of WD. RESULTS: According to Kaplan-Meier analysis, neurological WD
      patients scheduled for DPA had a similar probability of not remaining on first
      line therapy as patients receiving ZS (20% vs. 24% at the end of follow-up), with
      adjusted odds ratio (OR) of 0.9 (95% CI 0.2-3.5). In patients with hepatic WD,
      this probability was significantly higher for DPA (31% vs. 12%; adjusted OR 3.0,
      95% CI 0.9-9.9), especially in the first 6 months. Early worsening occurred only
      in neurological WD patients, with no differences between both treatment groups
      (35% vs. 19%; OR 2.8, 95% CI 0.7-10.8). Neurological improvement and decrease of
      liver enzymes were achieved with similar frequency. Compliance with DPA was
      better in hepatic (97% vs. 80%) but not in neurological patients (91% vs. 81%).
      Drug adverse effects were more common on DPA (15% vs. 3%). CONCLUSIONS: DPA and
      ZS are effective in the majority of WD patients. Neither therapy appears to be
      clearly superior. Therefore ZS may be considered a reasonable alternative to DPA
      as a first-line therapy.

PMID- 24447649
TI  - Cardiac safety of rasagiline, a selective monoamine oxidase type B inhibitor for
      the treatment of Parkinson's disease: a thorough QT/QTc study.
AB  - AIMS: Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor,
      developed for the treatment of Parkinson's disease. In compliance with current
      regulatory requirements, rasagiline underwent a thorough QT/QTc (TQT) study to
      assess its potential to prolong cardiac repolarization. The primary aim of this
      study was to evaluate the effects of clinical (1 mg/day) and supratherapeutic (2
      mg/day and 6 mg/day) multiple oral doses of rasagiline on the baseline- and
      placebo-adjusted QTc interval (delta delta QTc (ddQTc)). Other electrocardiogram
      parameters, pharmacokinetic assessments, safety and tolerability as well as vital
      signs were investigated. METHODS: This was a five-arm, randomized, double-blind,
      placebo- and active-controlled, and parallel study in healthy subjects.
      Moxifloxacin (400 mg) positive control was included to demonstrate assay
      sensitivity. RESULTS: 247 of 250 randomized subjects completed the study. Time
      matched analysis of ddQTc yielded two-sided 90% confidence intervals for all
      rasagiline doses below the 10 ms regulatory threshold, showing no effect on
      cardiac repolarization. Concentration-effect analysis demonstrated no
      relationships between rasagiline (and its metabolite 1-aminoindan), plasma
      concentrations, and ddQTc. The pharmacokinetic profile of rasagiline was
      consistent with previous studies. Adverse events were mild to moderate in
      intensity and were similar across all treatment groups. There were no clinically
      significant changes in heart rate and systolic blood pressure. CONCLUSION: This
      TQT study demonstrated a favorable cardiac safety profile of rasagiline.

PMID- 24447650
TI  - Age-distribution and genotype-phenotype correlation for N-acetyltransferase in
      Argentine children under isoniazid treatment.
AB  - INTRODUCTION: Metabolic clearance of isoniazid (INH) may be up to 10 times faster
      in individuals who are rapid acetylators compared with slow acetylators. In
      addition, the acetylation phenotype has been suggested to change with age. A
      better knowledge of the age distribution of the acetylation genotype and
      phenotype in children requiring INH for tuberculosis treatment or prevention
      could be important to optimize safety and efficacy of INH use. OBJECTIVES: The
      aim of the present study was to evaluate the genotype and phenotype of NAT2 in an
      Argentinean pediatric population rom Buenos Aires. In addition, we wanted to
      describe genotype-phenotype correlation, as well as its distribution at different
      ages. METHODOLOGY: NAT2 genotyping was performed by RFLP technique, searching for
      common polymorphisms. Acetylisoniazid and isoniazid concentrations were measured
      by HPLC and NAT2 phenotype was defined from the ratio of both concentrations
      (Metabolic Ratio, MR). RESULTS: Almost half of the patients (46.02%) possessed
      wild-type haplotype, with 17.05% of individuals having two fully functional
      alleles, 57.95% one fully functional allele and 25% with no fully functional
      allele. According to phenotype, most children (96.59%) were classified as fast
      acetylators, whereas 1.14% of the cases were intermediate and 2.27% slow
      acetylators. There was a positive association between age and MR (R = 0.52985, p
      < 0.000001) with a significant MR difference between age categories (p < 0.001).
      CONCLUSIONS: We found a high proportion of rapid acetylators compared with other
      populations. Acetylator phenotype showed a positive correlation with age, with a
      significant change around the 4th year of life.

PMID- 24447651
TI  - Effects of sugammadex on activated partial thromboplastin time and prothrombin
      time in healthy subjects.
AB  - OBJECTIVES: To assess the impact of sugammadex on activated partial
      thromboplastin time (APTT) and international normalized ratio for prothrombin
      time (PT(INR)) in healthy subjects and characterize the concentration-dependency
      of sugammadex effects on APTT and prothrombin time (PT) in normal human plasma in
      vitro. METHODS: Eight healthy subjects (18 - 45 years of age) were administered
      intravenous doses of 4 mg/kg sugammadex, 16 mg/kg sugammadex, or placebo in a
      randomized, placebo-controlled, three period cross-over trial. The primary
      endpoint was area under the curve from 2 to 60 minutes post-dose (AUC2-60min) for
      APTT and PT(INR). In vitro, the effects of sugammadex on APTT and PT were
      assessed in pooled normal human citrate plasma. RESULTS: In subjects dosed with 4
      and 16 mg/kg sugammadex, geometric mean ratios (treated vs. placebo) for AUC2
      60min were 1.085 (95% confidence interval, 0.888 - 1.325) and 1.019 (0.868 -
      1.195), respectively, for APTT, and 1.047 (0.904 - 1.213) and 1.096 (0.953 -
      1.261), respectively, for PT(INR). At individual timepoints, mean APTT and
      PT(INR) increased by up to 22% after 16 mg/kg sugammadex compared with placebo.
      All such increases occurred within 30 minutes post-dose. Sugammadex was generally
      well tolerated. In the in vitro experiments, addition of sugammadex to plasma
      resulted in limited, concentration dependent increases in both APTT and PT. At
      200 MUg/mL (the mean maximum concentration reached therapeutically), the relative
      increases were 29% and 19%, respectively. CONCLUSIONS: Administration of
      sugammadex is associated with a dose-related, limited and transient prolongation
      of APTT and PT(INR) that is unlikely to be of clinical relevance.

PMID- 24447652
TI  - Sequelae of early hospital readmission after kidney transplantation.
AB  - We recently elucidated risk factors for early hospital readmission (EHR)
      following kidney transplantation (KT). We now sought to quantify the independent
      associations between EHR and post-KT outcomes, including late hospital
      readmission (LHR: 1 year after EHR window), death-censored graft loss and
      mortality, among Medicare-primary KT recipients (2000-2005). Of 32961 KT
      recipients, 7.7% had at least one readmission within 3 days of discharge, 14.8%
      within 7 days, 22.4% within 14 days and 30.5% within 30 days of discharge after
      the initial KT hospitalization. KT recipients who experienced EHR within 30 days
      of discharge after the initial KT hospitalization were more likely to have
      experienced LHR (29.6% vs. 9.0%, p<0.001) and were at 3.02 times higher (95% CI:
      2.82-3.23, p<0.001) risk of LHR. Additionally, EHR was associated with death
      censored graft loss (deceased donor recipients hazard ratio [HR]: 1.43, 95% CI:
      1.36-1.51, p<0.001 and live donor recipients HR: 1.54, 95% CI: 1.40-1.70,
      p<0.001) and mortality (deceased donor recipients HR: 1.50, 95% CI: 1.43-1.58,
      p<0.001 and live donor recipients HR: 1.45, 95% CI: 1.32-1.60, p<0.001). Thirty
      days posttransplant represents a high-risk window for KT recipients and the
      readmissions during this window are strong predictors of adverse sequelae,
      particularly LHRs. Efforts should be made to implement and improve systems to
      reduce LHR and subsequent graft loss and mortality among recipients with EHR.

PMID- 24447653
TI  - Stable transmission of Dirofilaria repens nematodes, northern Germany.

PMID- 24447655
TI  - Dual mobility retentive acetabular liners and wear: surface analysis of 40
      retrieved polyethylene implants.
AB  - PURPOSE OF THE STUDY: Dual mobility systems with retentive acetabular liners have
      been used in clinical practice for total hip arthroplasty since 1976. The dual
      mobility system preserves a wide range of motion while providing greater
      stability. This study measured wear on the concave and convex surfaces of 40
      retrieved polyethylene liners, to evaluate the advantages of this system in
      relation to wear. MATERIAL AND METHODS: Forty polyethylene inserts that had been
      removed due to infection or mechanical failure after a mean 8 years were
      analyzed. The mean age of patients at arthroplasty was 46 years old. Macroscopic
      analysis was followed by surface analysis with direct measurement of changes in
      the curvature radii. The internal concave surface was measured in three
      dimensions using a 4-mm stylus (BNH 706). External convexity was measured by
      lateral projection. The estimated error was +/- 5 MUm for both measurement
      methods. Manufacturers' tolerance for these implants was approximately 50 MUm.
      Linear wear and wear volume was determined by comparing the measured dimensions
      with the theoretical dimensions of new liners. RESULTS: Macroscopically, all of
      the pieces studied had lost the initial machined grooves on the convex surface;
      40% of the pieces showed visible wear of the retentive collar. Mean annual convex
      surface wear was 9 MUm (SD 9MUm) and 73 MUm (SD 69 MUm) for the concave surface.
      Mean total wear, which was the sum of the wear on the convex and concave surfaces
      was 82 MUm (SD 72 MUm). Wear volume was 28.9 mm(3)/yr for the convex surface (SD
      27.6) and 25.5 for the concave surface (SD 23.2) with a mean annual total wear
      volume of 54.3 mm(3)/yr (SD 39.6). DISCUSSION: Total wear in the 40 dual mobility
      liners that had functioned in vivo was similar to that reported in metal
      polyethylene bearings with 22.2mm femoral heads. The results of wear in both the
      convex and concave surfaces show that wear with the dual mobility system was not
      increased compared to conventional metal-polyethylene bearings, while providing
      better retention and greater stability. CONCLUSION: The use of dual mobility
      acetabular liners is an attractive solution when a metal-polyethylene bearing is
      needed. The increased joint stability is not associated with increased wear.

PMID- 24447654
TI  - Adiponectin, chemerin, cytokines, and dipeptidyl peptidase 4 are released from
      human adipose tissue in a depot-dependent manner: an in vitro system including
      human serum albumin.
AB  - BACKGROUND: Adipose tissue (AT) contributes to metabolic dysfunction through
      imbalanced production of adipokines, including cytokines. Visceral AT in
      particular is associated with metabolic disorders, indicating a specific
      secretory status. The relative significance of different human AT depots in
      adipokine release is not fully known. Further, previous in vitro systems usually
      included medium containing bovine serum albumin (BSA), which may induce cytokine
      release. Our aim was to compare release of a number of adipokines/cytokines - all
      implicated in insulin resistance - from human subcutaneous and visceral AT in a
      short-term incubation system minimizing cytokine induction and including repeated
      measurements during 24 h. A prerequisite was to evaluate a potential alternative
      to BSA in the incubation medium. METHODS: Subcutaneous and/or visceral AT from 17
      patients (age 20-68 years; BMI 22.6-56.7 kg/m2) undergoing elective surgery was
      incubated for 2, 4, 6, 8, and 24 h in medium with or without 1% BSA or human
      serum albumin (HSA). Medium concentrations of adiponectin, chemerin, nine
      cytokines, dipeptidyl peptidase 4 (DPP4), and omentin were analyzed by multiplex
      immunoassay or ELISA. Adipocyte size, AT macrophage density, and medium
      concentrations of endotoxin were determined. RESULTS: Cytokine release was
      induced by BSA but not by HSA. In evaluation of the final incubation protocol
      including 1% HSA, and as expected, adiponectin release was higher from
      subcutaneous biopsies of nonobese than of obese subjects and inversely associated
      with adipocyte size; omentin was released almost exclusively from visceral AT.
      Exploratory incubations revealed more abundant release of chemerin, cytokines
      (except IL-6), and DPP4 from the visceral depot, while adiponectin release was
      higher from subcutaneous than visceral AT. Release was linear for a maximum of 2
      6 h. Macrophage density was higher in visceral than subcutaneous AT. Levels of
      endotoxin in the medium were negligible. CONCLUSIONS: Adiponectin, chemerin, many
      cytokines, and DPP4 are released from human AT in a depot-dependent manner. These
      results highlight functional differences between visceral and subcutaneous AT,
      and a mechanistic link between regional fat accumulation and metabolic disorders.
      Supplementation of human AT incubation medium with HSA rather than BSA is
      recommended to minimize induction of cytokine release.

PMID- 24447656
TI  - A new technic for segmental spinal osteosynthesis using the posterior approach.
AB  - The authors have designed a new method of instrumentation aimed at obtaining
      surgical fixation of the scoliotic curve without any postoperative external
      immobilisation. It is particularly strong and rigid and allows adequate reduction
      of the curve. This technique avoids the sublaminar space and thus prevents
      excessive blood loss and diminishes the danger of cord damage. The
      instrumentation is made of two parallel rough cylindrical rods inserted
      independently in the convexity and concavity of the curve. If necessary, they can
      be bent pre-operatively. They are attached to hooks placed on the laminae or
      pedicles, which are locked by bolts, thus allowing progressive straightening of
      the curve. They are joined by two transverse bars, one above and one below, to
      provide better rigidity to the device and to allow correction of rotation. The
      parts of the vertebrae left free by the device are denuded to allow the addition
      of grafts. Laboratory tests have demonstrated that this type of fixator is more
      rigid than the Harrington or Luque rods. Fifteen patients, either idiopathic or
      paralytic cases, were operated on without any neurological impairment. No loss of
      correction was observed since the hooks have been locked. 

PMID- 24447657
TI  - Annotated checklist and fisheries interactions of cetaceans in Togo, with
      evidence of Antarctic minke whale in the Gulf of Guinea.
AB  - Based on strandings and captures, 9 cetacean species, including 6 odontocetes and
      3 mysticetes, are documented (photos and specimens) in Togo's coastal waters
      (newly-recorded species marked with an asterisk): Antarctic minke whale
      (Balaenoptera bonaerensis*), Bryde's whale (Balaenoptera brydei or B. edeni),
      humpback whale (Megaptera novaeangliae), sperm whale (Physeter macrocephalus),
      pygmy sperm whale (Kogia breviceps*), short-finned pilot whale (Globicephala
      macrorhynchus*), pantropical spotted dolphin (Stenella attenuata*), common
      bottlenose dolphin (Tursiops truncatus) and common dolphin Delphinus sp. An
      anecdotal sighting record for killer whale (Orcinus orca) is considered reliable.
      The lack of Sousa teuszii records in Togo is consistent with its apparent
      contemporaneous absence in Ghana. The B. bonaerensis specimen, entangled in a
      purse seine set on small pelagics, is a first record for the Gulf of Guinea. The
      occurrence of this Southern Ocean species north of the equator underscores the
      severe gaps in our understanding of cetacean distribution off western Africa. The
      majority of artisanal fishermen operating in Togolese coastal waters are of
      Ghanaian origin and are thought to promote trade and consumption of cetacean
      bushmeat. Because captures are illegal, enforced with some success in the main
      fishing centers, covert landings of cetaceans are exceedingly difficult to
      monitor, quantify or sample. Concern is expressed about pollution of Togo's
      coastal waters with heavy metals due to phosphorite mining and export from the
      coastal basin near Hahotoe and Kpogame. 

PMID- 24447658
TI  - Environmental ethics: an overview, assessing the place of bioscientists in
      society, supplemented with selected Australian perspectives.
AB  - Ethics deals with moral behavior in a professional context; ideally, it leads to
      a set of governing principles through which the appropriateness of any activity
      may be determined or assessed. Environmental ethics specifically deals with how
      humans interact with the biosphere. It is clear, however, that, as a species, we
      are failing in our duty of environmental stewardship. The encroachment of human
      activity into the natural environment is inexorable, and almost always
      deleterious. Any response to mitigate loss of taxa or ecosystems will have
      economic implications, and these are often considerable. In finding effective
      solutions, a process soon becomes political. In light of this we must reflect
      upon the leadership role that biologists have, especially our impact on policy
      development that pertains to natural resource management. Although our track
      record is no worse than any other professional group, biologists by way of
      training usually have a greater understanding of natural processes and must be
      prepared to articulate these publically. We have an ethical mandate to question
      decisions, policies and legislation that impact negatively upon biological
      systems: a mandate guided through logic, grounded in empirical science, and
      hopefully coupled with a deep understanding of the true value of both the living
      world and the physical world which sustains it. This paper uses Australian
      examples to demonstrate the frequent clashes between economics and biology, in
      anticipation that we should strive to achieve the underlying principles of
      sustainability, environmental stewardship and resource management in both daily
      decision-making and in long-term planning. 

PMID- 24447659
TI  - Annual survival and site fidelity of free-ranging white-tailed deer (Odocoileus
      virginianus): comparative demography before (1983-1992) and after (1993-2005)
      spatial confinement.
AB  - Survival and movement are important demographic variables influencing the
      dynamics of large herbivores with implications for management and evolution of
      life-history strategies. Management practices such as spatial confinement and
      harvest regulation attempt to control survival and movement for the
      sustainability of harvested deer populations, but a paucity of long-term data
      exists on these management practices. We examined annual survival and site
      fidelity of free-ranging white-tailed deer (Odocoileus virginianus) over 10 years
      (1983-1992) to compare demographic parameters after spatial confinement (1993
      2005). We used capture records (n = 174; 104 females, 70 males), marked deer
      recaptures (n = 42), and dead recoveries (n = 68) to estimate sex-specific, age
      specific and time-specific parameters. We found that annual female survival was
      50% from 1983-1987 during a period of intense harvest, but increased to 93.7%
      after intense harvesting was eliminated. Prior to spatial confinement, annual
      survival of marked male deer averaged 36.7%-42.5%. After spatial confinement,
      annual survival increased on average for males (58%-99%) and females (77%-98%).
      Females showed high levels of site fidelity (>99%) prior to spatial confinement,
      whereas males showed much less site fidelity (<=4.5% for the 2 top-ranking
      models). During spatial confinement, the semi-impermeable fence effectively
      increased site fidelity of males (>=56%). These results stem from long-term study
      (23 years) of a large herbivore experiencing changes to life-history, resulting
      from changes in management that were applied to the population and aimed at
      altering population demographics, for sustainability of a harvestable population
      of deer. 

PMID- 24447660
TI  - Blue sheep in the Annapurna Conservation Area, Nepal: habitat use, population
      biomass and their contribution to the carrying capacity of snow leopards.
AB  - The Himalaya region of Nepal provides a habitat for the endangered snow leopard
      (Panthera uncia) and its principal prey species, the blue sheep (Pseudois
      nayaur). The aim of this study was to describe the habitat, the distribution and
      the population structure of blue sheep, and to estimate their contribution to the
      carrying capacity of snow leopard in the upper Mustang region of Nepal. Blue
      sheep were recorded at altitudes from 3209-5498 m on slopes with gradients of 16
      60 degrees  and aspects of 40 degrees NE to 140 degrees SE. A total of 939 blue
      sheep were counted in the upper Mustang region, and 98 were counted in the Yak
      Kharka region of Manang district; however, upper Mustang had the lowest
      population density of blue sheep recorded within their distribution range in
      Nepal (0.86 blue sheep/km(2)). The results of the study show that a higher
      density of blue sheep is associated with greater plant species diversity. The
      most important species present in the blue sheep habitat were Kobresia pygmaea,
      Artemesia spp., Lonicera spp., Lancea tibetica, Poa spp., Astragalus spp. and
      Ephedra gerardiana. It is estimated that the existing blue sheep population
      biomass of approximately 38 925 kg in the upper Mustang region could support
      approximately 19 snow leopards (1.6 snow leopards/100 km(2)).

PMID- 24447661
TI  - Ecological scale and seasonal heterogeneity in the spatial behaviors of giant
      pandas.
AB  - We report on the first study to track the spatial behaviors of wild giant pandas
      (Ailuropoda melanoleuca) using high-resolution global positioning system (GPS)
      telemetry. Between 2008 and 2009, 4 pandas (2 male and 2 female) were tracked in
      Foping Reserve, China for an average of 305 days (+/- 54.8 SE). Panda home ranges
      were larger than those of previous very high frequency tracking studies, with a
      bimodal distribution of space-use and distinct winter and summer centers of
      activity. Home range sizes were larger in winter than in summer, although there
      was considerable individual variability. All tracked pandas exhibited
      individualistic, unoriented and multiphasic movement paths, with a high level of
      tortuosity within seasonal core habitats and directed, linear, large-scale
      movements between habitats. Pandas moved from low elevation winter habitats to
      high elevation (>2000 m) summer habitats in May, when temperatures averaged 17.5 
      degrees C (+/- 0.3 SE), and these large-scale movements took <1 month to
      complete. The peak in panda mean elevation occurred in Jul, after which they
      began slow, large-scale movements back to winter habitats that were completed in
      Nov. An adult female panda made 2 longdistance movements during the mating
      season. Pandas remain close to rivers and streams during winter, possibly
      reflecting the elevated water requirements to digest their high-fiber food. Panda
      movement path tortuosity and first-passage-time as a function of spatial scale
      indicated a mean peak in habitat search effort and patch use of approximately 700
      m. Despite a high degree of spatial overlap between panda home ranges,
      particularly in winter, we detected neither avoidance nor attraction behavior
      between conspecifics. 

PMID- 24447662
TI  - Effects of larval size and hydrodynamics on the growth rates of the black fly
      Simulium tribulatum.
AB  - Black flies are ubiquitous and important members of lotic ecosystems. Size is
      known to affect many aspects of their life in the aquatic larval stage, including
      intraspecific competition for feeding sites. As filter feeders, flow affects
      their ability to feed and reach sufficiently fast flow. This, in turn, can lead
      to risky fluid-mediated dispersal behavior in search of better conditions. It is
      surprising, therefore, that little information is available regarding how
      physiological and environmental factors combine to affect larval growth rates.
      The present study determines the relative growth rates of small (0.6 mm) and
      large (approximately 4 mm) larvae in laboratory flumes designed to produce
      spatially homogeneous and temporally consistent flow regimes at ecologically
      relevant velocities (44 and 64 cm/s). Our results indicate that size and flow
      both influence growth rates and that the 2 interact significantly. Young larvae
      exhibit faster growth rates and a greater positive response to increased flow
      speed. This result might help explain why smaller larvae have a greater
      propensity to disperse than larger larvae: the benefit of increased growth rate
      that they receive from relocating to faster flow might balance the risks inherent
      in dispersal. 

PMID- 24447663
TI  - Perceptions of fishers to sea turtle bycatch, illegal capture and consumption in
      the San Ignacio-Navachiste-Macapule lagoon complex, Gulf of California, Mexico.
AB  - In this study, 10% of all registered fishermen in the coastal towns of Navachiste
      in Sinaloa, in northwestern Mexico, answered a survey designed to collect data on
      their perceptions of the following topics: the impact of turtle meat consumption;
      human health; bycatch; illegal turtle fishing; the illegal sea turtle market; the
      local economy; pollution; environmental education; the success of protective
      legislation; and sea turtle-based ecotourism. Perceptions were analyzed using the
      fuzzy logic method through classification into 5 fuzzy membership sets: VL, very
      low; L, low; M, moderate; H, high; VH, very high. The 9 topics generated decision
      areas upon applying fuzzy inference that revealed the membership level of the
      answers in each fuzzy set. The economic potential of sea turtle-based ecotourism
      and the economic profitability of the illegal turtle meat market were perceived
      as VL. Conservation legislation was perceived as H, although inefficiently
      applied due to corruption. Ecotourism and impacts on sea turtles were perceived
      as VL, because they were deemed unprofitable activities at the individual and
      community levels. Environmental education was perceived as L, because it centers
      on nesting, hatching and releasing turtles and is directed at elementary and
      middle-school students. While fishers perceive a serious negative impact of
      fishing activities on sea turtles in the San Ignacio-Navachiste-Macapule area,
      they do not see themselves individually as part of the problem. Achieving sea
      turtle conservation in this region requires: suitable ecotourism infrastructure,
      government investments in promotion, and studies to estimate the minimum number
      of tourists needed to assure profitability. 

PMID- 24447664
TI  - Phenotypic plasticity is maintained despite geographical isolation in an African
      cichlid fish, Pseudocrenilabrus multicolor.
AB  - Gene flow among populations in different selective environments should favor the
      evolution of phenotypic plasticity over local adaptation. Plasticity in
      development is a common response to long-term hypoxia in some widespread African
      fishes, including Pseudocrenilabrus multicolor, a cichlid that exploits both
      normoxic (high oxygen) rivers/lakes and hypoxic (low oxygen) swamps. Previous
      studies have shown that fish from normoxic and hypoxic sites differ in many
      traits, including gill size, brain size and body shape, and that much of this
      variation reflects developmental plasticity. However, these earlier studies
      focused on areas in Uganda where gene flow between swamp and river or lake
      populations is high. In this study we tested the hypothesis that P. multicolor
      from a relatively isolated lake population (Lake Saka, Uganda) exhibit low levels
      of plasticity in traits related to oxygen uptake. Multiple broods of P.
      multicolor from Lake Saka were reared under low and high dissolved oxygen, and
      traits related to gill size, brain mass and body shape were quantified.
      Surprisingly, both gill size and brain mass showed high levels of developmental
      plasticity. We suggest that high levels of plasticity, particularly in the gill
      size of P. multicolor, reflects low costs of maintaining the plastic response,
      even in relatively isolated populations. 

PMID- 24447665
TI  - Bird community comparisons of four plantations and conservation concerns in South
      China.
AB  - Plantations of non-native, fast-growing trees are increasing in the tropics and
      subtropics, perhaps with negative consequences for the native avifauna. We
      studied bird diversity in 4 types of plantations in South China to determine
      which plantation types are especially detrimental, and compared our findings with
      studies in nearby natural forests to assess the magnitude of the negative impact.
      A total of 57 species was recorded. The mean capture rate of understory birds was
      1.7 individuals 100-net-h(-1). Bird richness and capture rate were lower in
      plantations than in nearby natural forests. Babblers (Timaliidae), primarily
      forest-dependent species in South China, were particularly under-represented in
      plantations. Species richness, composition and bird density, particularly of
      understory birds, differed between plantation types. Plantations of Schima, which
      is native to South China, had the highest species richness according to point
      count data. Plantations of Acacia (non-native) supported the highest understory
      species richness and produced the highest capture rate of understory birds,
      probably because of their complex structure and high arthropod abundance. If bird
      diversity is to be considered, we strongly recommend that future re-afforestation
      projects in South China should, as far as possible, use mixed native tree
      species, and especially Schima, ahead of the other species.

PMID- 24447667
TI  - A common variant in pre-miR-146 is associated with coronary artery disease risk
      and its mature miRNA expression.
AB  - miRNAs are small non-coding RNAs that play an important role in numerous
      physiological processes. Common single nucleotide polymorphisms (SNPs) in pre
      miRNAs may change their property through altering miRNAs expression and/or
      maturation, resulting in diverse functional consequences. To date, the role of
      genetic variants in pre-miRNAs on coronary artery disease (CAD) risk remains
      poorly understood. Here we aimed to evaluate the influence of three common SNPs
      in pre-miRNAs (miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, miR-499
      rs3746444 T>C) on individual susceptibility to CAD in a Chinese population of 295
      CAD patients and 283 controls. Genotyping was performed using polymerase chain
      reaction-based restriction fragment length polymorphism (PCR-RFLP) method. In a
      logistic regression analysis, we detected an association of rs2910164 in pre-miR
      146a with the CAD risk; compared with the GG homozygotes, the GC heterozygotes
      [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.06-3.36, P=0.029] and the
      CC homozygotes (OR=1.83, 95% CI=1.01-3.32, P=0.046) genotype were statistically
      significantly associated with the increased risk for CADs. As we used further
      genotype association models, we found a similar trend of the association in
      recessive model (OR=1.86, 95% CI=1.09-3.19, P=0.023). We also found that the
      genotypes of miR-146a rs2910164 were associated with its mature miRNA expression
      by analyzing 23 PBMC samples from CAD patients. Individuals carrying rs11614913
      GC or CC genotypes showed 3.2-fold higher expression compared to GG genotype
      carriers (P<0.05). We observed no association of the other two SNPs in miR-196a2
      (rs11614913) and miR-499 (rs3746444) with the CAD incidence. Our data provide the
      first evidence that the miR-146a rs2910164 polymorphism is associated with
      increased risk of CAD in Chinese Han population, which may be through influencing
      the expression levels of the miRNA. 

PMID- 24447668
TI  - Tritrichomonas foetus: prevalence study in naturally mating bulls in Switzerland.
AB  - Switzerland is officially free from bovine Tritrichomonas foetus. While bulls
      used for artificial insemination (AI) are routinely examined for this pathogen,
      bulls engaged in natural mating, as well as aborted fetuses, are only very
      sporadically investigated, indicating that the disease awareness for bovine
      tritrichomoniasis is low. Natural mating in cattle is becoming increasingly
      popular in Switzerland. Accordingly, a re-introduction/re-occurrence of T. foetus
      in cattle seems possible either via resurgence from a yet unknown bovine
      reservoir, or via importation of infected cattle. The low disease awareness for
      bovine tritrichomoniasis might favor an unnoticed re-establishment of T. foetus
      in the Swiss cattle population. The aim of our study was thus to search for the
      parasite, and if found, to assess the prevalence of bovine T. foetus in
      Switzerland. We included (1) bulls over two years of age used in natural mating
      and sent to slaughter, (2) bulls used for natural service in herds with or
      without fertility problems and (3) aborted fetuses. Furthermore, the routinely
      examined bulls used for AI (4) were included in this study. In total, 1362
      preputial samples from bulls and 60 abomasal fluid samples of aborted fetuses
      were analyzed for the presence of T. foetus by both in vitro cultivation and
      molecular analyses. The parasite could not be detected in any of the samples,
      indicating that the maximal prevalence possibly missed was about 0.3% (95%
      confidence). Interestingly, in preputial samples of three bulls of category 1,
      apathogenic Tetratrichomonas sp. was identified, documenting a proof-of-principle
      for the methodology used in this study. 

PMID- 24447669
TI  - [Soft-tissue mass as a rare presentation of sarcoidosis].
AB  - BACKGROUND: The most important differential diagnosis of a soft-tissue mass is
      soft-tissue sarcoma, and the diagnostic process should be aimed at diagnosing or
      excluding this. CASE DESCRIPTION: A 28-year-old man was referred to the surgeon
      with a progressive painless swelling on the right shoulder. Diagnostic imaging
      suggested a sarcoma with axillary lymphadenopathy. Repeatedly biopsy revealed a
      non-necrotizing granulomatous inflammation. A diagnosis of sarcoidosis was
      finally made, after exclusion of malignancy and infectious causes. CONCLUSION:
      When a patient presents with a soft-tissue mass, malignant causes such as soft
      tissue sarcoma should be excluded. If pathological investigation reveals a
      granulomatous inflammation, a soft-tissue mass as a rare presentation of
      sarcoidosis should be considered. It is, however, important to first exclude a
      sarcoid-like reaction.

PMID- 24447670
TI  - [Introduction of next-generation sequencing in health care: what are the
      implications for physicians and patients?].
AB  - Next-generation sequencing (NGS) involves the laying down of the sequence of the
      entire genome or exome at one time. This technique is expected to become one of
      the approaches in diagnostic testing. The genetically determined vulnerability of
      individuals to disorder and their response to treatment can be determined at one
      go. However, this gives rise to ethical and legal questions, particularly in the
      area of the protection of patient privacy. These questions include provision of
      information to the patient about the DNA investigation and the chance of
      incidental findings, feedback to the patient concerning incidental findings and
      the storage and reuse of the genetic information. It is important to begin
      discussion of the legal and ethical consequences of NGS investigations at an
      early stage. This article may be the stimulus for this discussion. 

PMID- 24447671
TI  - [Rectal bleeding during pregnancy].
AB  - BACKGROUND: Ischaemic colitis is a relatively rare disease that predominantly
      affects elderly patients. This disorder has varying underlying causes and diverse
      clinical symptoms. CASE DESCRIPTION: A 29-year-old primigravida was admitted to
      our hospital with rectal bleeding and diffuse abdominal pain. The number of
      leucocytes and the CRP were elevated. Because the patient was pregnant a
      sigmoidoscopy without sedation was performed. The endoscopic image and
      histopathology of the biopsies revealed ischaemic colitis. Our patient recovered
      quickly under conservative treatment. CONCLUSION: Ischaemic colitis is usually
      self-limiting and a conservative treatment will suffice. Ischaemic colitis during
      pregnancy has been reported extremely rarely and the aetiology is unknown.

PMID- 24447672
TI  - [General practitioner and palliative sedation].
AB  - Recent publications in Dutch national newspapers on palliative sedation have
      raised concerns about its use in general practice. There is now evidence that
      there is no significant increase in the incidence of palliative sedation.
      Euthanasia requests were pending in 20.8% of the cases in which palliative
      sedation was performed, but the general practitioners could clearly justify why
      they made this choice. This is important because it indicates that they are aware
      of a sharp distinction between euthanasia and palliative sedation. Although the
      decision to perform palliative sedation was discussed with almost all cancer
      patients, patient involvement was less present in non-cancer conditions. This may
      be related to different disease trajectories, but it also indicates that
      attention should be devoted to earlier identification of patients in need of
      palliative care. The findings confirm that the practice of palliative sedation by
      general practitioners largely reflects the recommendations of the Dutch National
      Guideline on Palliative Sedation. 

PMID- 24447673
TI  - [The benefit of braces in adolescent idiopathic scoliosis].
AB  - Recently, the Bracing in Adolescent Idiopathic Scoliosis Trial made an important
      contribution to the continuing debate about the effectiveness of bracing for
      idiopathic scoliosis. The investigators concluded that the use of a brace
      significantly reduces the risk of progression of the curves beyond 50 degrees,
      and thus the risk of having to undergo surgery. Unfortunately, their original
      randomized trial design had to be abandoned at an early stage of the study.
      Instead, an extra arm was added in which the patients could choose between
      treatment in a brace and observation. Ultimately, 52% of the study population was
      included in this non-randomized arm, 71% of whom chose a brace. Apart from this
      criticism on the performance of the study, one may wonder whether a curve of 50
      degrees at the end of growth can really be considered a good result of treatment.

PMID- 24447675
TI  - [Consequences of next-generation sequencing: does sharing information mean
      spreading sorrow?].
AB  - With the advent of next-generation sequencing, rapid and affordable whole genome
      sequencing will become readily available in clinical practice. Considering the
      major implications of this technology in everyday clinical work, clinicians need
      to be informed and should be involved in the process of developing national
      guidelines on this subject. 

PMID- 24447676
TI  - [Payment for accepting depot medication].
AB  - Non-compliance with medication constitutes a large problem in medicine. Recently
      the results of a cluster randomised controlled trial were published in which
      financial incentives were offered to patients with psychotic disorders. The
      objective of this study was to test if financial incentives effectively improved
      adherence to maintenance treatment with depot antipsychotics. The financial
      incentives increased acceptance of depot medication but did not lead to any
      clinical benefits. Therefore, the implementation of contingency management using
      financial incentives is not yet desirable. 

PMID- 24447677
TI  - Mediation analysis of the relationship between institutional research activity
      and patient survival.
AB  - BACKGROUND: Recent studies have suggested that patients treated in research
      active institutions have better outcomes than patients treated in research
      inactive institutions. However, little attention has been paid to explaining such
      effects, probably because techniques for mediation analysis existing so far have
      not been applicable to survival data. METHODS: We investigated the underlying
      mechanisms using a recently developed method for mediation analysis of survival
      data. Our analysis of the effect of research activity on patient survival was
      based on 352 patients who had been diagnosed with advanced ovarian cancer at 149
      hospitals in 2001. All hospitals took part in a quality assurance program of the
      German Cancer Society. Patient outcomes were compared between hospitals
      participating in clinical trials and non-trial hospitals. Surgical outcome and
      chemotherapy selection were explored as potential mediators of the effect of
      hospital research activity on patient survival. RESULTS: The 219 patients treated
      in hospitals participating in clinical trials had more complete surgical
      debulking, were more likely to receive the recommended platinum-taxane
      combination, and had better survival than the 133 patients treated in non-trial
      hospitals. Taking into account baseline confounders, the overall adjusted hazard
      ratio of death was 0.58 (95% confidence interval: 0.42 to 0.79). This effect was
      decomposed into a direct effect of research activity of 0.67 and two indirect
      effects of 0.93 each mediated through either optimal surgery or chemotherapy.
      Taken together, about 26% of the beneficial effect of research activity was
      mediated through the proposed pathways. CONCLUSIONS: Mediation analysis allows
      proceeding from the question "Does it work?" to the question "How does it work?"
      In particular, we have shown that the research activity of a hospital contributes
      to superior patient survival through better use of surgery and chemotherapy. This
      methodology may be applied to analyze direct and indirect natural effects for
      almost any combination of variable types.

PMID- 24447678
TI  - Diagnostic value of biparametric magnetic resonance imaging (MRI) as an adjunct
      to prostate-specific antigen (PSA)-based detection of prostate cancer in men
      without prior biopsies.
AB  - OBJECTIVES: To determine the diagnostic yield of analysing biparametric (T2- and
      diffusion-weighted) magnetic resonance imaging (B-MRI) for prostate cancer
      detection compared with standard digital rectal examination (DRE) and prostate
      specific antigen (PSA)-based screening. PATIENTS AND METHODS: Review of patients
      who were enrolled in a trial to undergo multiparametric-prostate (MP)-MRI and
      MR/ultrasound fusion-guided prostate biopsy at our institution identified 143 men
      who underwent MP-MRI in addition to standard DRE and PSA-based prostate cancer
      screening before any prostate biopsy. Patient demographics, DRE staging, PSA
      level, PSA density (PSAD), and B-MRI findings were assessed for association with
      prostate cancer detection on biopsy. RESULTS: Men with detected prostate cancer
      tended to be older, with a higher PSA level, higher PSAD, and more screen
      positive lesions (SPL) on B-MRI. B-MRI performed well for the detection of
      prostate cancer with an area under the curve (AUC) of 0.80 (compared with 0.66
      and 0.74 for PSA level and PSAD, respectively). We derived combined PSA and MRI
      based formulas for detection of prostate cancer with optimised thresholds. (i)
      for PSA and B-MRI: PSA level + 6 x (the number of SPL) > 14 and (ii) for PSAD and
      B-MRI: 14 * (PSAD) + (the number of SPL) >4.25. AUC for equations 1 and 2 were
      0.83 and 0.87 and overall accuracy of prostate cancer detection was 79% in both
      models. CONCLUSIONS: The number of lesions positive on B-MRI outperforms PSA
      alone in detection of prostate cancer. Furthermore, this imaging criteria coupled
      as an adjunct with PSA level and PSAD, provides even more accuracy in detecting
      clinically significant prostate cancer.

PMID- 24447679
TI  - Mycoepoxydiene inhibits activation of BV2 microglia stimulated by
      lipopolysaccharide through suppressing NF-kappaB, ERK 1/2 and toll-like receptor
      pathways.
AB  - Mycoepoxydiene (MED) is a polyketide isolated from the marine fungal Diaporthe
      sp. HLY-1 associated with mangroves. Although MED has been shown to have various
      biological effects such as antimicrobial, anti-cancer, and anti-inflammatory
      activities, its activities and cellular mechanisms during microglial activation
      have yet to be elucidated. In the present study, we assessed the anti
      inflammatory effect of MED on the production of inflammatory mediators in
      lipopolysaccharide (LPS)-stimulated murine BV2 microglia. MED significantly
      inhibited LPS-induced production of pro-inflammatory mediators such as tumor
      necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6
      (IL-6), interferon-gamma (INF-gamma), and nitric oxide (NO), whereas it increased
      anti-inflammatory interleukin-10 (IL-10) and transforming growth factor-beta1
      (TGF-beta1) production in BV2 microglia in a concentration-dependent manner
      without causing cytotoxicity. Moreover, MED suppressed NF-kappaB activation by
      blocking IkappaB-alpha (IkappaB-alpha) degradation and inhibited the
      phosphorylation of ERK 1/2 and toll-like receptor 4 (TLR4) expression, but had no
      effect on the phosphorylation of JNK, and p38. Our results demonstrate that the
      inhibitory and promotion effect of MED on LPS-stimulated inflammatory mediators
      and anti-inflammatory factor production in BV2 microglia is associated with the
      suppression of the NF-kappaB, ERK1/2 and TLR signaling pathways. Therefore, MED
      may have therapeutic potential for neurodegenerative diseases by inhibiting
      inflammatory mediators and enhancing anti-inflammatory factor production in
      activated microglia. 

PMID- 24447680
TI  - Shikonin inhibits the lipopolysaccharide-induced release of HMGB1 in RAW264.7
      cells via IFN and NF-kappaB signaling pathways.
AB  - To study the anti-inflammation effect of Shikonin (Shik) and its mechanism,
      murine macrophage-like RAW264.7 cells (RAW264.7 cells) were divided into control
      group, LPS group (0.125, 0.25 and 0.5MUg/ml), LPS (0.125, 0.25 and 0.5MUg/ml)
      plus Shik (0.5, 1 and 2MUM) group, and Shik (2MUM) group. After exposure for 24h,
      the levels of Interleukin-6 (IL-6), nitric oxide (NO) and Tumor Necrosis Factor
      alpha (TNF-alpha) in supernatant were measured with ELISA, the expression of high
      mobility group box 1(HMGB1) in supernatant and cytoplasm was assayed using qRT
      PCR, western blot and immunofluorescence assays, the expression of IFN-beta in
      cellular and supernatant was assayed by qRT-PCR and ELISA, and the ratio of
      nuclear to cytoplasm for NF-kappaB protein expression was assayed using western
      blot. The results of our investigation demonstrated that Shik could reduce
      significantly the levels of IL-6, NO and TNF-alpha in RAW264.7 cells exposed to
      LPS (P<0.05 or P<0.01). The expression of HMGB1, IFN-beta and the ratio of
      nuclear to cytoplasm for NF-kappaB protein expression in LPS plus Shik group
      declined significantly as compared with LPS group (P<0.05 or P<0.01). The
      inhibitors of IFN-beta signaling molecule JAK and NF-kappaB could attenuate
      significantly the expression of HMGB1 in supernatant. It was found in the present
      study that Shik could have the anti-inflammatory effects in RAW264.7 cells
      exposed to LPS, and one of the mechanisms may be the down-regulation of HMGB
      expression, which was associated with the IFN-beta and NF-kappaB signaling
      pathways. 

PMID- 24447681
TI  - Cassane-type diterpenoids from the seed kernels of Caesalpinia bonduc.
AB  - Seven new cassane diterpenoids (1-7), along with three known compounds (8-10),
      were isolated from the seed kernels of Caesalpinia bonduc. The structures were
      elucidated by extensive 1D and 2D NMR (HSQC, HMBC and ROESY) and mass (HRESIMS)
      spectroscopic data analyses. The structure and absolute configuration of compound
      1 were confirmed by a single-crystal X-ray diffraction experiment. All isolates
      were tested for their cytotoxicity against HepG-2, MCF-7 and MG-63 cells, and 8
      10 showed weak inhibitory activities. 

PMID- 24447684
TI  - When does an enlarged cervical lymph node in a child need excision? A systematic
      review.
AB  - BACKGROUND: Palpable cervical lymphadenopathy is very common in children. The
      clinician's job is to exclude malignancy as a cause and reach a diagnosis. In
      children selected for open biopsy, reactive hyperplasia and other inflammatory
      causes are far more common as a final diagnosis than malignancy. Furthermore
      complications can occur after open biopsy. OBJECTIVE: To assess the diagnostic
      utility of clinical examination and investigations to exclude malignancy and
      other serious causes of paediatric cervical lymphadenopathy and minimise open
      biopsy. TYPE OF REVIEW: A systematic review of the literature with defined search
      strategy. SEARCH STRATEGY: A structured search of Medline, Embase, CINAHL and
      Cochrane databases. The references within standard paediatric ENT and head and
      neck textbooks were also examined. RESULTS: The quality of evidence regarding
      predictors of malignancy is poor. Large lymph nodes and supraclavicular nodes are
      potential indicators of serious pathology. Fever, weight loss and organomegaly
      may be indicators but duration of symptoms and consistency are not. Abnormalities
      on chest X-ray are associated with serious causes but the diagnostic utility of
      routine chest X-ray is unknown. Ultrasound assessment of nodal architecture,
      margins, and shape (and possibly vascularity) shows considerable promise as a
      means of differentiating reactive hyperplasia from malignancy but further studies
      in children are required. Abnormalities in the full blood count (FBC) seem to be
      uncommon but when present are associated with serious causes of cervical
      lymphadenopathy, again the diagnostic utility is unclear. Serological testing may
      identify a specific cause and therefore avoid excision biopsy in around 10% of
      cases. Cutting needle biopsy requires further evaluation before it can be
      recommended. Fine needle aspiration cytology (FNAC) is very specific, but
      sensitivity varies in different studies to the extent that it cannot yet be
      relied upon to exclude malignancy. CONCLUSIONS: Large and supraclavicular nodes
      should be biopsied. Ultrasound is likely to be useful but further study is
      required. FNAC cannot be relied upon to exclude malignancy in children. The
      diagnostic utility of chest X-ray and FBC are unclear. Work is required on
      multivariate predictive models.

PMID- 24447685
TI  - Validation of the Screening Test for Auditory Processing (STAP) on school-aged
      children.
AB  - OBJECTIVES: The present study focussed on validating the Screening Test for
      Auditory Processing (STAP) that contains four subsections: speech-in-noise,
      dichotic consonant vowel, gap detection and auditory memory. The sensitivity and
      specificity were ascertained by comparing the results of the screening test with
      that of diagnostic tests for auditory processing. METHODS: The STAP was
      administered on 500 school going children in the age range of 8-13 years. These
      consisted of 141 children who were found at-risk on the Screening Checklist for
      Auditory Processing (SCAP). Diagnostic APD tests (speech-in-noise, dichotic CV,
      gap detection and auditory memory) were administered on 152 of the children
      referred and/or passed on the screening procedures. RESULTS: The results from the
      STAP indicated that the auditory memory subsection of the STAP was the most
      affected followed by dichotic CV and speech-in-noise. Gap detection was the least
      affected among the four subsections. A high and significant correlation was noted
      between the subsections of the STAP and the APD diagnostic tests. The sensitivity
      and specificity of the STAP on comparison with the diagnostic tests was found to
      be 76.6% and 72%, respectively. It was found that when a combination of SCAP and
      STAP was used for screening, the sensitivity and specificity were higher.
      CONCLUSION: Based on the findings of the study, it is recommended that both SCAP
      and STAP be administered. Further, there was also a good test-retest reliability
      of the SCAP, STAP and the APD diagnostic tests.

PMID- 24447683
TI  - Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared
      with alpha-glucosidase inhibitor in Japanese patients with type 2 diabetes
      inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter,
      randomized, open-label, non-inferiority trial.
AB  - We assessed the efficacy and safety of sitagliptin compared with alpha
      glucosidase inhibitor (alphaGI) in 120 of Japanese patients with type 2 diabetes
      mellitus (T2DM) inadequately controlled on stable <=2 mg/day glimepiride alone
      [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non
      inferiority trial. Patients were randomly assigned to receive additional
      sitagliptin or alphaGI for 24 weeks. The primary endpoint was change in HbA1c
      from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p
      < 0.001) relative to alphaGI. At 24 weeks, the reduction was almost identical
      between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more
      common with alphaGI than with sitagliptin, but only minor hypoglycaemia occurred
      in both groups at similar frequency. These data suggested that sitagliptin was
      not inferior to alphaGI for reduction of HbA1c in Japanese T2DM patients
      receiving glimepiride alone, and well tolerated with minimum risk of
      gastrointestinal symptoms and hypoglycaemia. 

PMID- 24447686
TI  - Low dose of rFSH [100 IU] in controlled ovarian hyperstimulation response: a
      pilot study.
AB  - BACKGROUND: The initial dose of recombinant Follicle Stimulating Hormone [rFSH]
      to be used in assisted reproduction treatment depends on several factors, mainly
      the cause of the infertility and the patient's age. For young patients [<=35
      years] usually an initial dose of around 150 IU of rFSH is recommended, but there
      are no studies proving that this should actually be the standard initial dose. We
      aimed to report the experience of a low-cost Human Reproduction Center where a
      dose of 100 IU of rFSH was used for controlled ovarian hyperstimulation [COH].
      FINDINGS: An observational prospective study was performed on 212 women aged <=38
      years old that underwent high-complexity assisted reproduction treatments. The
      patients' infertility was mainly caused by tuboperitoneal, idiopathic or male
      factors. Controlled ovarian stimulation was performed using 100 IU of rFSH.
      Regarding the COH, 53.8% of the patients presented a satisfactory response, 25.9%
      low response, 14.2% hyper-response, and 6.1% developed ovarian hyperstimulation
      syndrome. Of the 55 patients with poor response, 20 started a new cycle with an
      initial dose of 200 IU of rFSH; 65% showed a satisfactory response, 10% a poor
      response, 20% a hyper-response, and 5% developed OHSS. CONCLUSION: The initial
      dose of 100 IU of rFSH was considered adequate for controlled ovarian
      hyperstimulation, meeting the aim to reduce the costs of the assisted
      reproduction treatment.

PMID- 24447687
TI  - Impedimetric sensor of bacterial toxins based on mixed (Concanavalin
      A)/polyaniline films.
AB  - In this paper, we report the use of Concanavalin A (ConA) and electrosynthesized
      polyaniline (PANI) thin films for the development of a new electrochemical sensor
      that allows the specific detection of two bacterial toxins: lipopolysaccharide
      (LPS) from Escherichia coli and lipoteichoic acid from Staphylococcus aureus. The
      impedimetric sensor is fabricated by using glutaraldehyde to self-assemble ConA
      lectin on PANI-modified steel electrodes through covalent binding. ConA acts as a
      recognition element for bacterial toxins. Electrical impedance spectroscopy (EIS)
      and scanning electron microscope (SEM) were applied to characterize the assembly
      process on the modified electrode. The EIS measurements revealed that the
      resistance charge transfer (RCT) of the electrode/electrolyte interface increases
      considerably after the ConA lectin interacts with specific carbohydrate moieties
      present in the molecule of the bacterial toxin. Our results showed that the ConA
      lectin retained its activity after immobilization on the PANI surface and also
      the existence of electrochemical impedance response of the bioelectrode which is
      linear to the extent of the lectin-toxin interaction, with maximum values of RCT
      for E. coli (14.40 kOmega), and S. aureus (17.80 kOmega). We have observed that
      electrosynthesized PANI is an excellent support layer for the covalent binding of
      lectins on the electrode surface. Thus, the recognition system provides an
      appropriate biomimetic interface for detection of specific constituents of gram
      positive and gram-negative bacteria.

PMID- 24447688
TI  - Open or laparoscopic living donor liver hepatectomy: still a challenging
      operation!

PMID- 24447689
TI  - Andes hantavirus variant in rodents, southern Amazon Basin, Peru.
AB  - We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and
      identified an Andes virus variant from Neacomys spinosus mice. This finding
      extends the known range of this virus in South America and the range of
      recognized hantaviruses in Peru. Further studies of the epizoology of
      hantaviruses in this region are warranted. 

PMID- 24447690
TI  - Observational study of regional aortic size referenced to body size: production
      of a cardiovascular magnetic resonance nomogram.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) is regarded as the gold
      standard for clinical assessment of the aorta, but normal dimensions are usually
      referenced to echocardiographic and computed tomography data and no large CMR
      normal reference range exists. As a result we aimed to 1) produce a normal CMR
      reference range of aortic diameters and 2) investigate the relationship between
      regional aortic size and body surface area (BSA) in a large group of healthy
      subjects with no vascular risk factors. METHODS: 447 subjects (208 male, aged 19
      70 years) without identifiable cardiac risk factors (BMI range 15.7-52.6 kg/m2)
      underwent CMR at 1.5 T to determine aortic diameter at three levels: the
      ascending aorta (Ao) and proximal descending aorta (PDA) at the level of the
      pulmonary artery, and the abdominal aorta (DDA), at a level 12 cm distal to the
      PDA. In addition, 201 of these subjects had aortic root imaging, allowing for
      measurements at the level of the aortic valve annulus (AV), aortic sinuses and
      sinotubular junction (STJ). RESULTS: Normal diameters (mean +/-2 SD) were; AV
      annulus male(?) 24.4 +/- 5.4, female (?) 21.0 +/- 3.6 mm, aortic sinus? 32.4 +/-
      7.7, ?27.6 +/- 5.8 mm, ST-junction ?25.0 +/- 7.4, ?21.8 +/- 5.4 mm, Ao ?26.7 +/-
      7.7, ?25.5 +/- 7.4 mm, PDA ?20.6 +/- 5.6, +18.9 +/- 4.0 mm, DDA ?17.6 +/- 5.1,
      ?16.4 +/- 4.0 mm. Aortic root and thoracic aortic diameters increased at all
      levels measured with BSA. No gender difference was seen in the degree of
      dilatation with increasing BSA (p>0.5 for all analyses). CONCLUSION: Across both
      genders, increasing body size is characterized by a modest degree of aortic
      dilatation, even in the absence of traditional cardiovascular risk factors.

PMID- 24447691
TI  - [Acute sensory-motor axonal neuropathy (Guillain-Barre syndrome) following
      vertebroplasty].

PMID- 24447692
TI  - [Tobacco consumption during pregnancy].

PMID- 24447693
TI  - [Reply].

PMID- 24447694
TI  - Ectopic pituitary adenoma associated with an empty sella presenting with hearing
      loss: case report with literature review.
AB  - Ectopic pituitary adenomas are uncommon entities that may pose substantial
      diagnostic challenges. In the majority of these cases, patients present with
      endocrine and/or nasal obstruction symptoms. We report the case of an ectopic
      pituitary adenoma in a 76-year-old man with an empty sella who initially
      presented with right-sided hearing loss progressing to bilateral hearing loss
      over the next 4 years. Neuroimaging studies revealed a large, expansile central
      skull base mass replacing the clivus and sphenoid sinus, and invading the
      internal auditory canals and inner ear bilaterally. The tumor also involved the
      floor of the middle cranial fossae and bilateral medial temporal and occipital
      bones. Histopathologic examination, including immunohistochemical studies,
      revealed a sparsely granulated lactotroph adenoma. Hearing loss in a patient with
      ectopic pituitary adenoma constitutes an extremely unusual presentation. This
      case was further complicated by the presence of an empty sella and the absence of
      symptoms related to hyperprolactinemia. 

PMID- 24447695
TI  - Relationship between the MDS-UPDRS domains and the health-related quality of life
      of Parkinson's disease patients.
AB  - BACKGROUND AND PURPOSE: The Movement Disorder Society sponsored version of the
      Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive
      instrument for assessing Parkinson's disease (PD). The present study was aimed at
      determining the relationships between MDS-UPDRS components and health-related
      quality of life (HRQoL) evaluations in PD patients. METHODS: An international,
      multicenter, cross-sectional study was carried out of 435 PD patients assessed
      with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ
      5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation
      coefficients, exploratory factor analysis and multiple linear regression models
      (dependent variables EQ-5D and PDQ-8) were performed. RESULTS: The participants'
      age was 66.71 +/- 10.32 years (51.5% men). PD duration was 8.52 +/- 6.14, and
      median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS
      UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from
      0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS
      UPDRS domains as independent variables, the main determinant for both the EQ-5D
      index and the PDQ-8 was Part II followed by Part I. After factorial grouping of
      the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for
      inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and
      fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes.
      CONCLUSIONS: The MDS-UPDRS component most tightly related with the HRQoL measures
      was a combination of motor and non-motor experiences of daily living.

PMID- 24447698
TI  - Ultrastructural morphology of the reproductive swarmers of Sphaerozoum punctatum
      (Huxley) from the East China Sea.
AB  - Reproductive swarmers of the polycystine radiolarian Sphaerozoum punctatum
      (Huxley) collected from the East China Sea were examined using light, scanning
      and transmission electron microscopy. The swarmer cells were about 8-10 MUm in
      length with a pear-like shape and a conical end with two flagella. A nucleus,
      mitochondria, Golgi body, lipid droplets and, characteristically, a single,
      large, vacuole-bound SrSO4 crystal were present in the cytoplasm. Centering on
      the crystal inclusion, swarmers swam in a rapid rotational movement both
      clockwise and anticlockwise. Small subunit (SSU) rDNA sequences obtained for the
      reproductive swarmer cells from S. punctatum show a monophyletic group together
      with colonial spumellarians and grouped with S. punctatum from Bermuda in the
      clade. The morphological features and molecular phylogeny of the reproductive
      swarmers of S. punctatum show evidence of ancestral traits of radiolarians;
      acantharians and polycystines have a common ancestry. In addition, SrSO4
      inclusion of the swarmer cell may be a form of ballast deposited by the swarmer
      to allow proper positioning in the water column. We hypothesize that radiolarian
      affiliated sequences from SSU rDNA clone libraries of marine picoeukaryotes may
      be derived from the picoplanktonic cells of radiolarians; i.e., small flagellated
      life stages such as reproductive swarmers or gametes.

PMID- 24447699
TI  - Predictors of non-participation in cervical screening in Denmark.
AB  - PURPOSE: The aims of this study were to identify demographic and socio-economic
      predictors of non-participation in cervical screening in Denmark, and to evaluate
      the influence of health care use on screening participation. METHODS: A
      population based register study was undertaken using data from the Central
      Population Register, the national Patobank, and Statistics Denmark. The study
      included women aged 25-54 years on 1st of January 2002, living in Denmark during
      the next 5 years, and without a history of total hysterectomy, N=1,052,447.
      Independent variables included age, civil status, nationality, level of
      education, and use of health care. Associations with non-participation in
      screening were determined with logistic regression. RESULTS: Main predictors of
      non-participation were limited or no contact with dental services (odds ratio
      (OR)=2.36), general practitioners (OR=1.75), and high age (OR=1.98). Other
      important factors for non-participation were primary school education only
      (OR=1.53), not being married (OR=1.49), and foreign nationality (OR=1.32).
      CONCLUSION: A 2-1.5-fold difference in non-participation in cervical screening in
      Denmark was found across various population sub-groups. Increased screening
      compliance among women with primary school education only, and limited or no use
      of primary health care services in general could potentially diminish the current
      social inequalities in cervical cancer incidence, and thus decrease the overall
      high incidence of this disease in Denmark.

PMID- 24447700
TI  - Estimating the cure proportion of malignant melanoma, an alternative approach to
      assess long term survival: a population-based study.
AB  - OBJECTIVES: A large proportion of patients with cutaneous malignant melanoma
      (CMM) do not experience excess mortality due to their disease. This group of
      patients is referred to as the cure proportion. Few studies have examined the
      possibility of cure for CMM. The aim of this study was to estimate the cure
      proportion of patients with CMM in a Swedish population. METHODS: We undertook a
      population-based study of 5850 CMM patients in two Swedish health care regions
      during 1996-2005. We used flexible parametric cure models to estimate cure
      proportions and median survival times (MSTs) of uncured by stage, sex, age and
      anatomical site. RESULTS: Disease stage at diagnosis was the most important
      factor for the probability of cure, with a cure proportion of approximately 1.0
      for stage IA. While the probability of cure decreased with older age, the
      influence of age was smaller on the MST of uncured. Differences in prognosis
      between males and females were mainly attributed to differences in cure as
      opposed to differences in MST of uncured. CONCLUSIONS: This population-based
      study showed approximately 100% cure among stage IA disease. Almost 50% of
      patients had stage IA disease and the high cure proportion for this large patient
      group is reassuring.

PMID- 24447701
TI  - Age-related bone turnover markers and osteoporotic risk in native Chinese women.
AB  - BACKGROUND: The rate of bone turnover is closely related to osteoporosis risk. We
      investigated the correlation between bone turnover markers and BMD at various
      skeletal sites in healthy native Chinese women, and to study the effect of
      changes in the levels of bone turnover markers on the risk of osteoporosis.
      METHODS: A cross-section study of 891 healthy Chinese women aged 20-80 years was
      conducted. The levels of serum osteocalcin (OC), bone-specific alkaline
      phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen
      (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary
      NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were
      determined. BMD at the posteroanterior spine and the hip was measured using DXA.
      RESULTS: Pearson's correlation coefficient found significant negative correlation
      between bone turnover marker and BMD T-score at different skeletal sites (r = 
      0.08 to -0.52, all P = 0.038-0.000). After adjustments for age and body mass
      index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and
      uCTX, and the T-scores at various skeletal sites were still significant. After
      adjustment of height and weight, the correlation coefficients between most BTMs
      and PA lumbar spine BMD were also significant. Multiple linear regression
      analysis showed that bone turnover markers were negative determinants of T
      scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores
      of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4
      21.9% of the variations in the femoral neck and total hip T-scores. The bone
      turnover marker levels were grouped as per quartile intervals, and the T-scores,
      osteoporosis prevalence and risk were found to markedly and increase with
      increase in bone turnover marker levels. CONCLUSIONS: This study clarified the
      relationship between bone turnover markers and osteoporosis risk in native
      Chinese women. Bone turnover marker levels were found to be important
      determinants of BMD T-scores. Furthermore, osteoporotic risk significantly
      increased with increase in the levels of bone turnover markers.

PMID- 24447704
TI  - Growth inhibition and coordinated physiological regulation of zebrafish (Danio
      rerio) embryos upon sublethal exposure to antidepressant amitriptyline.
AB  - Amitriptyline is a tricyclic antidepressant used for decades. It is present at
      low detectable concentrations in the aquatic environment, but relative few
      studies have focused on its ecotoxicological effects on non-target aquatic
      animals. The present study conducted an acute toxicity test of waterborne
      amitriptyline exposure using zebrafish (Danio rerio) embryos 4 to 124 h-post
      fertilization. Time-dependent lethal concentrations were firstly determined and
      at mg/L levels. Effects of amitriptyline on zebrafish embryos were then evaluated
      under amitriptyline exposure at sublethal concentrations of 1, 10, 100 ng/L, 1,
      10, 100 MUg/L and 1mg/L. Our results showed that amitriptyline significantly
      reduced the hatching time and body length of embryos after exposure in a
      concentration-dependent manner. Our study also revealed that the exposure evoked
      a coordinated modulation of physiological and biochemical parameters in exposed
      zebrafish embryos, including alterations of adrenocorticotropic hormone (ACTH)
      level, oxidative stress and antioxidant parameters, as well as nitric oxide (NO)
      production and total nitric oxide synthase (TNOS) activity. A U-shaped
      concentration-dependent response curve was observed in ACTH level in response to
      amitriptyline exposure. However, both U-shaped and inversed U-shaped curves were
      indicated in the responses of antioxidant parameters, including total antioxidant
      capacity, antioxidant enzyme activities (catalase, superoxide dismutase and
      peroxidase), glutathione content and glutathione reductase activity.
      Correspondingly, hydroxyl radical formation and lipid peroxidation indices
      changed in similar U-shaped concentration-dependent patterns, which together the
      results of antioxidant parameters suggested induction of oxidative stress in
      embryos exposed to amitriptyline at high concentrations. Moreover, NO production
      and TNOS activity were both significantly affected by amitriptyline exposure.
      Notably, significant correlations between these measured parameters were
      revealed, which suggested a dynamic adaptation process and coordinated regulation
      of multiple physiological systems in fish embryos to amitriptyline treatment.
      Furthermore, our study demonstrated that the effective concentrations of
      amitriptyline for measured parameters in zebrafish embryos were as low as 10
      ng/L, and thus revealed the potential risk of amitriptyline and other
      antidepressants to aquatic life.

PMID- 24447702
TI  - A comparison of two systems of patient immobilization for prostate radiotherapy.
AB  - BACKGROUND: Reproducibility of different immobilization systems, which may affect
      set-up errors, remains uncertain. Immobilization systems and their corresponding
      set-up errors influence the clinical target volume to planning target volume (CTV
      PTV) margins and thus may result in undesirable treatment outcomes. This study
      compared the reproducibility of patient positioning with Hipfix system and whole
      body alpha cradle with respect to localized prostate cancer and investigated the
      existing CTV-PTV margins in the clinical oncology departments of two hospitals.
      METHODS: Forty sets of data of patients with localized T1-T3 prostate cancer were
      randomly selected from two regional hospitals, with 20 patients immobilized by a
      whole-body alpha cradle system and 20 by a thermoplastic Hipfix system. Seven
      sets of the anterior-posterior (AP), cranial-caudal (CC) and medial-lateral (ML)
      deviations were collected from each patient. The reproducibility of patient
      positioning within the two hospitals was compared using a total vector error
      (TVE) parameter. In addition, CTV-PTV margins were computed using van Herk's
      formula. The resulting values were compared to the current CTV-PTV margins in
      both hospitals. RESULTS: The TVE values were 5.1 and 2.8 mm for the Hipfix and
      the whole-body alpha cradle systems respectively. TVE associated with the whole
      body alpha cradle system was found to be significantly less than the Hipfix
      system (p < 0.05). The CC axis in the Hipfix system attained the highest
      frequency of large (23.6%) and serious (7.9%) set-up errors. The calculated CTV
      to PTV margin was 8.3, 1.9 and 2.3 mm for the Hipfix system, and 2.1, 3.4 and 1.8
      mm for the whole body alpha cradle in CC, ML and AP axes respectively. All but
      one (CC axis using Hipfix) margin calculated did not exceed the corresponding
      hospital protocol. The whole body alpha cradle system was found to be
      significantly better than the Hipfix system in terms of reproducibility (p <
      0.05), especially in the CC axis. CONCLUSIONS: The whole body alpha cradle system
      was more reproducible than the Hipfix system. In particular, the difference in CC
      axis contributed most to the results and the current CC margin for the Hipfix
      system might be considered as inadequate.

PMID- 24447706
TI  - Clinical method today.

PMID- 24447705
TI  - Sequence variation among members of the miR-200 microRNA family is correlated
      with variation in the ability to induce hallmarks of mesenchymal-epithelial
      transition in ovarian cancer cells.
AB  - BACKGROUND: Epithelial-Mesenchymal Transition (EMT) is a transient and reversible
      (Mesenchymal-Epithelial Transition or MET) process by which epithelial cells
      acquire mesenchymal cell characteristics including reduced intercellular adhesion
      and increased cell motility. While EMT/MET has long been recognized as an
      essential component of early embryonic development, there is a growing body of
      evidence indicating that EMT/MET is also a key component of ovarian cancer (OC)
      metastasis. Recent findings have implicated members of the miR-200 family of
      microRNAs (miRNAs) in this process. METHODS: Individual members of the miR-200
      family of miRNAs were transiently over expressed in metastatic (mesenchymal-like)
      OC cell lines. Changes in morphology, molecular profiles and drug sensitivity
      were monitored relative to cells transfected with a negative control. RESULTS:
      Morphological hallmarks of MET were detected in cells transfected with all miR
      200 family members. Gene expression profiling demonstrated up regulation of
      epithelial biomarkers and down regulation of mesenchymal biomarkers in
      transfected cells although significant variation in molecular response and drug
      sensitivity was associated with different members of the miR-200 family.
      CONCLUSIONS: Our results indicate that although ectopic overexpression of all
      members of the miR-200 family in mesenchymal-like OC cells results in
      morphological changes characteristic of MET, the underlying molecular changes and
      induced drug sensitivities are highly variable and correlated with sequence
      variation within the seed and non-seed regions of individual family members.

PMID- 24447707
TI  - Commentary on Mercer-Jones et Al.

PMID- 24447708
TI  - A preliminary study of transcaecal ileostomy as an alternative to defunctioning
      ostomies.
AB  - AIM: To evaluate the usefulness of a transcaecal ileostomy catheter for
      protecting distal lower rectal anastomosis as an alternative to conventional
      ileostomy. METHOD: Patients with a rectal cancer located 3-10 cm from the anal
      verge were included in the study. In all cases, an open low or ultra-low anterior
      resection of the rectum was performed with total mesorectal excision. A balloon
      catheter was inserted through the caecum and ileocaecal valve, with the
      catheter's distal end placed in terminal ileum. A computed tomography (CT) scan
      was performed 7 days postoperatively to check the integrity of the anastomosis;
      the transcaecal catheter was withdrawn if no complications were detected.
      RESULTS: Eighteen patients were treated with a transcaecal catheter. Two patients
      developed cellulitis (11.1%) in the catheter exit wound. In both cases,
      successful healing was achieved within a month of surgery. One patient had
      anastomotic dehiscence (5.5%) after removal of the catheter following a normal CT
      examination. The median hospital stay was 10 days (range 8-13 days). CONCLUSION:
      A transcaecal ileostomy catheter to protect a distal rectal anastomosis is a
      potential alternative to loop ileostomy with potentially fewer complications and
      without need for a second procedure for closure.

PMID- 24447709
TI  - Re: Fluid administration in bowel surgery.

PMID- 24447714
TI  - Changes in management and outcome of patients with rectal cancer in Northern
      Ireland: 1996-2006.
AB  - AIM: This study aimed to document developments in rectal cancer services in a UK
      population and evaluate changes in outcome over a 10-year period. METHOD:
      Patients diagnosed with primary rectal carcinoma in 1996, 2001 and 2006 were
      identified by the Northern Ireland Cancer Registry. Data were retrospectively
      collected on presentation, investigation, treatment and staging. Differences over
      the period were analysed using the chi-squared test; Kaplan-Meier and Cox
      regression tests were used for survival analysis. RESULTS: After exclusions there
      were 636 patients, including 187 presenting in 1996, 203 in 2001 and 246 in 2006.
      The use of preoperative MRI of the rectum, endorectal ultrasound and abdominal CT
      increased during the study period. For patients treated by surgery, total
      mesorectal excision (TME) increased from 19% in 1996 to 64% in 2006 (P < 0.001).
      The use of radiotherapy (27% in 1996, 47% in 2006) and chemotherapy (21% in 1996,
      32% in 2006) increased. The overall 5-year survival improved significantly
      between 1996 and 2006 from 34% in 1996 to 45% in 2006 (P = 0.02). Among patients
      having surgery, 5-year survival increased from 43% in 1996 to 63% in 2006 (P <
      0.001). Multivariate analysis showed that the improvement in survival was
      associated with TME and chemotherapy, while radiotherapy was not. CONCLUSION:
      Survival of patients with rectal cancer in Northern Ireland has improved
      significantly over the last decade, probably due to the increased use of TME and
      chemotherapy.

PMID- 24447715
TI  - UWA-121, a mixed dopamine and serotonin re-uptake inhibitor, enhances L-DOPA anti
      parkinsonian action without worsening dyskinesia or psychosis-like behaviours in
      the MPTP-lesioned common marmoset.
AB  - L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective treatment for
      Parkinson's disease (PD), but its long-term administration is complicated by
      wearing-off and dyskinesia. UWA-101, a dual, equipotent inhibitor of dopamine
      (DAT) and serotonin (SERT) transporters, has previously been shown to
      successfully extend duration of anti-parkinsonian benefit of L-DOPA (ON-time),
      without exacerbating dyskinesia, in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-lesioned marmoset. However, UWA-101 is racemic and it
      is unclear whether one or both enantiomers contribute to its actions, and whether
      a better therapeutic effect might be attained by using a single antipode. In the
      current study, we synthesised the two enantiomers of UWA-101, R-101 (UWA-121) and
      S-101 (UWA-122), characterised their pharmacological profiles and administered
      them to MPTP-lesioned marmosets. Parkinsonism, dyskinesia, psychosis-like
      behaviours and duration of ON-time were evaluated. UWA-121 is a dual DAT > SERT
      inhibitor, with an approximate 10:1 DAT:SERT affinity ratio (inhibitory constants
      (Ki) of 307 and 3830 nM, respectively). In combination with L-DOPA, UWA-121
      extended duration of ON-time when compared to L-DOPA/vehicle treatment (by 40%, P
      < 0.01). UWA-121 also extended duration of ON-time without dyskinesia (by 215%, P
      < 0.05) and ON-time without psychosis-like behaviours when compared to L
      DOPA/vehicle treatment (by 345%, P < 0.01). UWA-121 did not worsen the severity
      of dyskinesia or psychosis-like behaviours (P > 0.05). UWA-122 is a selective
      SERT inhibitor (Ki 120 nM, Ki at DAT > 50 MUM) and, in combination with L-DOPA,
      had no effect on ON-time, dyskinesia or psychosis-like behaviours (P > 0.05).
      These data indicate that dual DAT and SERT inhibitors effectively enhance L-DOPA
      anti-parkinsonian action without worsening dyskinesia and that compounds with
      such a pharmacological profile represent promising agents against wearing-off in
      PD.

PMID- 24447716
TI  - Cognition and the compassion deficit: the social psychology of helping behaviour
      in nursing.
AB  - This paper discusses compassion failure and compassion deficits in health care,
      using two major reports by Robert Francis in the UK as a point of reference.
      Francis enquired into events at the Mid Staffordshire Hospital between 2005 and
      2009, events that unequivocally warrant the description 'appalling care'. These
      events prompted an intense national debate, along with proposals for significant
      changes in the regulation of nursing and nurse education. The circumstances are
      specific to the UK, but the issues are international. I suggest that social
      psychology provides numerous hints about the mechanisms that might have been
      involved at Mid Staffs and about the reasons why outsiders are blind to these
      mechanisms. However, there have been few references to social psychology in the
      post-Francis debate (the Francis Report itself makes no reference to it at all).
      It is an enormously valuable resource, and it has been overlooked. Drawing on the
      social psychology literature, I express scepticism about the idea that there was
      a compassion deficit among the Mid Staff nurses - the assumption that the
      appalling care had something to do with the character, attitudes, and values of
      nurses - and argue that the Francis Report's emphasis on a 'culture of compassion
      and caring in nurse recruitment, training and education' is misconceived. It was
      not a 'failure of compassion' that led to the events in Mid Staffs but an
      interlocking set of contextual factors that are known to affect social cognition.
      These factors cannot be corrected or compensated for by teaching ethics, empathy,
      and compassion to student nurses. 

PMID- 24447718
TI  - Promoting a research culture among junior radiation oncologists: outcomes from
      the introduction of the Australian and New Zealand research requirement in
      training.
AB  - AIM: Since 2005, radiation oncology trainees in Australia and New Zealand have
      had to undertake a piece of original research during training, and submit a
      manuscript, as first author, for senior peer-review. Satisfactory completion of
      this requirement is one component of eligibility to sit the Royal Australian and
      New Zealand College of Radiologists Fellowship examinations. The purpose of this
      study was to examine the value of this curriculum requirement, including the
      publication rates and potential barriers to trainee research. MATERIALS AND
      METHODS: An online survey was sent to 116 radiation oncologists/trainees who
      trained since the mandatory research requirement was introduced (2005-2011).
      Questions concerned research topics, publications, subsequent research activity,
      perceptions on barriers to research and aids to conducting research during
      training. A web-based search of PubMed by author name was carried out to complete
      and verify publication statistics. RESULTS: In total, 108 (93.1%) of the 116
      trainees across 20 centres who submitted their research papers to the Radiation
      Oncology Faculty Research Committee were successful in meeting the required
      standard first time. Half of these trainees ultimately published their paper in a
      peer-reviewed journal. Of trainees responding to the survey, 62% presented their
      research at a scientific meeting. Most of the studies were either retrospective
      (62.3%) or dosimetry/physics projects (10.1%). The main problems encountered in
      conducting projects were competing clinical commitments and lack of dedicated
      research time. Notably, long ethics approval processes, lack of supervision and
      statistical support for projects were not considered barriers. CONCLUSION: This
      mandatory research requirement ensures trainees initiate and complete at least
      one project during their training. Since the introduction of this curriculum
      component, half of the research projects have resulted in publication in a peer
      reviewed journal. Increased 'protected time' and training in scientific writing
      and methods may improve publication rates and quality. This first review of the
      Australian and New Zealand radiation oncology trainee research requirement
      highlights areas that need to be addressed to further support and foster a
      research culture among junior radiation oncologists.

PMID- 24447717
TI  - Upregulated miR-182 increases drug resistance in cisplatin-treated HCC cell by
      regulating TP53INP1.
AB  - Chemotherapy plays a crucial role in hepatocellular carcinoma (HCC) treatment
      especially for patients with advanced HCC. Cisplatin is one of the commonly used
      chemotherapeutic drugs for the treatment of HCC. However, acquisition of
      cisplatin resistance is common in patients with HCC, and the underlying mechanism
      of such resistance is not fully understood. In the study, we focused on
      identifying the role of miRNAs in chemotherapy resistance after cisplatin-based
      combination chemotherapy. We assayed the expression level of miR-182 after
      cisplatin-based chemotherapy in patients with advanced HCC, and defined the
      biological functions by real-time PCR analysis and CCK-8 assay. We found that miR
      182 levels were significantly increased in HCC patients treated with cisplatin
      based chemotherapy. miR-182 levels were also higher in cisplatin-resistant HepG2
      (HepG2-R) cells than in HepG2 cells. Upregulated miR-182 significantly increased
      the cell viability, whereas miR-182 knockdown reduced the cell viability during
      cisplatin treatment. miR-182 inhibition also partially overcame cisplatin
      resistance in HepG2-R cell. Furthermore, we found that upregulated miR-182
      inhibited the expression of tumor suppressor gene TP53INP1 (tumor protein 53
      induced nuclear protein 1) in vitro. In vivo, miR-182 and TP53INP1 expression was
      negatively correlated. We finally demonstrated that miR-182 increased cisplatin
      resistance of HCC cell, partly by targeting TP53INP1. These data suggest that miR
      182/TP53INP1 signaling represents a novel pathway regulating chemoresistance,
      thus offering a new target for chemotherapy of HCC.

PMID- 24447719
TI  - Detection of small (<= 2 cm) pancreatic adenocarcinoma and surrounding
      parenchyma: correlations between enhancement patterns at triphasic MDCT and
      histologic features.
AB  - BACKGROUND: The aim is to assess the time-density curves (TDCs) and correlate the
      histologic results for small (<= 2 cm) PDA and surrounding parenchyma at
      triphasic Multidetector-row CT (MDCT). METHODS: Triphasic MDCT scans of 38
      consecutive patients who underwent surgery for a small PDA were retrospectively
      reviewed. The TDCs were analyzed and compared with histologic examination of the
      PDA and pancreas upstream/downstream in all cases. Three enhancement patterns
      were identified: 1) enhancement peak during pancreatic parenchymal phase (PPP)
      followed by a rapid decline on portal venous phase (PVP) and delayed phase (DP)
      at 5 minutes (type 1 pattern: normal pancreas); 2) maximum enhancement in PVP
      that gradually decreases in DP (type 2 pattern: mild chronic pancreatitis or PDA
      with mild fibrous stroma); 3) progressive enhancement with maximum peak in DP
      (type 3 pattern: severe chronic pancreatitis or PDA with severe fibrous stroma).
      A p value less than 0.05 was considered statistically significant. Sensitivity
      was calculated for PDA detection and an attenuation difference with the
      surrounding tissue of at least 10 HU was considered. RESULTS: PDA showed type 2
      pattern in 5/38 cases (13.2%) and type 3 pattern in 33/38 cases (86,8%). Pancreas
      upstream to the tumor had type 2 pattern in 20/38 cases (52,6%) and type 3
      pattern in 18/38 cases (47,4%). Pancreas downstream to the tumor had type 1
      pattern in 19/25 cases (76%) and type 2 pattern in 6/25 cases (24%). Attenuation
      difference between tumor and parenchyma upstream was higher of 10 UH on PPP in
      31/38 patients (sensitivity = 81.6%), on PVP in 29/38 (sensitivity = 76.3%) and
      on DP in 17/38 (sensitivity = 44.7%). Attenuation difference between tumor and
      parenchyma downstream was higher of 10 UH on PPP in 25/25 patients (sensitivity =
      100%), on PVP in 22/25 (sensitivity = 88%) and on DP in 20/25 (sensitivity =
      80%). Small PDAs were isodense to the pancreas upstream to the tumor, and
      therefore unrecognizable, in 8 cases (8/38; 21%) at qualitative analysis and in 4
      cases (4/38; 10,5%) at quantitative analysis. CONCLUSIONS: The quantitative
      analysis increases the sensitivity for detection of small PDA at triphasic MDCT.

PMID- 24447720
TI  - HLA antibodies in ATGs.

PMID- 24447721
TI  - Human cutaneous anthrax, Georgia 2010-2012.
AB  - We assessed the occurrence of human cutaneous anthrax in Georgia during 2010-
      2012 by examining demographic and spatial characteristics of reported cases.
      Reporting increased substantially, as did clustering of cases near urban centers.
      Control efforts, including education about anthrax and livestock vaccination, can
      be directed at areas of high risk. 

PMID- 24447723
TI  - Validation of a new ELISA method for in vitro potency testing of hepatitis A
      vaccines.
AB  - The goal of the project was to standardise a new in vitro method in replacement
      of the existing standard method for the determination of hepatitis A virus
      antigen content in hepatitis A vaccines (HAV) marketed in Europe. This became
      necessary due to issues with the method used previously, requiring the use of
      commercial test kits. The selected candidate method, not based on commercial
      kits, had already been used for many years by an Official Medicines Control
      Laboratory (OMCL) for routine testing and batch release of HAV. After a pre
      qualification phase (Phase 1) that showed the suitability of the commercially
      available critical ELISA reagents for the determination of antigen content in
      marketed HAV present on the European market, an international collaborative study
      (Phase 2) was carried out in order to fully validate the method. Eleven
      laboratories took part in the collaborative study. They performed assays with the
      candidate standard method and, in parallel, for comparison purposes, with their
      own in-house validated methods where these were available. The study demonstrated
      that the new assay provides a more reliable and reproducible method when compared
      to the existing standard method. A good correlation of the candidate standard
      method with the in vivo immunogenicity assay in mice was shown previously for
      both potent and sub-potent (stressed) vaccines. Thus, the new standard method
      validated during the collaborative study may be implemented readily by
      manufacturers and OMCLs for routine batch release but also for in-process control
      or consistency testing. The new method was approved in October 2012 by Group of
      Experts 15 of the European Pharmacopoeia (Ph. Eur.) as the standard method for in
      vitro potency testing of HAV. The relevant texts will be revised accordingly.
      Critical reagents such as coating reagent and detection antibodies have been
      adopted by the Ph. Eur. Commission and are available from the EDQM as Ph. Eur.
      Biological Reference Reagents (BRRs). 

PMID- 24447722
TI  - Developing Effective and Efficient care pathways in chronic Pain: DEEP study
      protocol.
AB  - BACKGROUND: Pain affecting the face or mouth and lasting longer than three months
      ("chronic orofacial pain", COFP) is relatively common in the UK. This study aims
      to describe and model current care pathways for COFP patients, identify areas
      where current pathways could be modified, and model whether these changes would
      improve outcomes for patients and use resources more efficiently. METHODS/DESIGN:
      The study takes a prospective operations research approach. A cohort of primary
      and secondary care COFP patients (n = 240) will be recruited at differing stages
      of their care in order to follow and analyse their journey through care. The
      cohort will be followed for two years with data collected at baseline 6, 12, 18,
      and 24 months on: 1) experiences of the care pathway and its impacts; 2) quality
      of life; 3) pain; 4) use of health services and costs incurred; 5) illness
      perceptions. Qualitative in-depth interviews will be used to collect data on
      patient experiences from a purposive sub-sample of the total cohort (n = 30) at
      baseline, 12 and 24 months. Four separate appraisal groups (public, patient,
      clincian, service manager/commissioning) will then be given data from the pathway
      analysis and asked to determine their priority areas for change. The proposals
      from appraisal groups will inform an economic modelling exercise. Findings from
      the economic modelling will be presented as incremental costs, Quality Adjusted
      Life Years (QALYs), and the incremental cost per QALY gained. At the end of the
      modelling a series of recommendations for service change will be available for
      implementation or further trial if necessary. DISCUSSION: The recent white paper
      on health and the report from the NHS Forum identified chronic conditions as
      priority areas and whilst technology can improve outcomes, so can simple,
      appropriate and well-defined clinical care pathways. Understanding the
      opportunity cost related to care pathways benefits the wider NHS. This research
      develops a method to help design efficient systems built around one condition
      (COFP), but the principles should be applicable to a wide range of other chronic
      and long-term conditions.

PMID- 24447724
TI  - Collaborative study for the establishment of the 3rd international standard for
      neomycin.
AB  - An international collaborative study was organised to establish the World Health
      Organization (WHO) 3(rd) International Standard (IS) for neomycin. Ten
      laboratories from different countries participated in the collaborative study.
      The potency of the candidate material, a freeze-dried preparation, was estimated
      by microbiological assays with sensitive micro-organisms. To ensure continuity
      between consecutive batches, the 2(nd) IS for neomycin was used as a standard.
      Based on the results of the study, the 3(rd) IS for neomycin was adopted at the
      meeting of the WHO Expert Committee on Biological Standardization (ECBS) in 2012
      with an assigned potency of 19,050 IU per vial. The 3(rd) IS for neomycin is
      available from the European Directorate for the Quality of Medicines & HealthCare
      (EDQM).

PMID- 24447725
TI  - Type 2 diabetes prevalence, health status and quality of care among the North
      African immigrant population living in France.
AB  - AIM: This report is an overview of type 2 diabetes (DT2) in the North African
      immigrant population living in France. METHODS: Data were collected in two
      separate cross-sectional national surveys. DT2 prevalence was estimated using a
      population-based survey involving 13 959 people aged >= 45 years (EDS), while
      health status and quality of care were evaluated using a sample of 3894 DT2
      patients (ENTRED). RESULTS: Prevalence of DT2 and obesity was 14.0% [CI 95%: 9.9;
      18.0] and 20.5% [15.7; 25.3], respectively, in participants born in North Africa
      (BNA) and 7.5% [7.0; 8.0] and 15.8% [14.7; 16.8], respectively, in those born in
      France (BIF). DT2 was associated with region of birth in women after adjusting
      for age, body mass index and income or occupation, but not after adjusting for
      education level. In men, DT2 was not associated with region of birth. BNA and BIF
      patients with diabetes frequently benefited from free medical coverage (88% vs.
      84%, respectively), although BNA diabetic patients visited a general practitioner
      less frequently than BIF (8.5 vs. 9.0 visits/year, respectively). The percentage
      of BNA vs. BIF diabetes patients tested three times a year for HbA1c was lower
      (39% vs. 44%), while HbA1c was higher in BNA vs. BIF diabetics (> 8%: 30% vs.
      15%). Ophthalmological complications were also more frequent in BNA vs. BIF
      patients with diabetes (25% vs. 18%, respectively). CONCLUSION: The greater
      prevalence of DT2 in BNA women and the poorer glycaemic control observed in the
      BNA population overall both probably contribute to disparity in diabetes
      mortality compared with BIF diabetics, a fact that has been observed in previous
      studies.

PMID- 24447726
TI  - Cardiovascular and ride time-to-exhaustion effects of an energy drink.
AB  - BACKGROUND: Currently, there are few studies on the cardiovascular and fatigue
      effects of commercially available energy drinks. This study investigated the
      effects of Monster energy drink (Monster Beverage Corporation, Corona,
      California), on resting heart rate (HR), heart rate variability (HRV), ride time
      to-exhaustion, peak exercise HR, respiratory exchange ratio (RER), and peak
      rating of perceived exertion (RPE). METHODS: The study used a double-blind,
      randomized, placebo controlled, crossover design. After an 8-hr fast, 15 subjects
      consumed Monster Energy Drink (ED standardized to 2.0 mg * kg-1 caffeine) or a
      flavor-matched placebo preexercise. Resting HR and HRV were determined. After an
      initial submaximal workload for 30 minutes, subjects completed 10 min at 80%
      ventilatory threshold (VT) and rode until volitional fatigue at 100% VT. RESULTS:
      Resting HR was significantly different (ED: 65+/-10 bpm vs. placebo: 58+/-8 bpm,
      p = 0.02), but resting HRV was not different between the energy drink and placebo
      trials. Ride time-to-exhaustion was not significantly different between trials
      (ED: 45.5+/- 9.8 vs. placebo: 43.8+/-9.3 min, p = 0.62). No difference in peak
      RPE (ED: 9.1 +/- 0.5 vs. placebo: 9.0 +/- 0.8, p = 1.00) nor peak HR (ED: 177 +/-
      11 vs. placebo: 175 +/- 12, p = 0.73) was seen. The RER at 30% of VT was
      significantly different (ED: 0.94 +/- 0.06 vs. placebo: 0.91 +/- 0.05, p =
      0.046), but no difference between the two conditions were seen at the other
      intensities. CONCLUSION: Although preexercise ingestion of the energy drink does
      increase resting HR there was no alteration in HRV parameters. Ride time-to
      exhaustion was not enhanced.

PMID- 24447727
TI  - Higher baseline international normalized ratio value correlates with higher
      mortality in intracerebral hemorrhage during warfarin use.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most feared
      complication of oral anticoagulation (OAC). Our aim was to investigate the impact
      of the international normalized ratio (INR) level on mortality in OAC-associated
      ICH compared with non-OAC-associated ICH. METHODS: A retrospective chart review
      of consecutive ICH patients treated at the Helsinki University Central Hospital
      from January 2005 to March 2010 (n = 1013) was performed. An ICH was considered
      to be OAC-associated if the patient was on warfarin at ICH onset. The association
      of INR with 3-month mortality was adjusted in a multivariable logistic regression
      model for factors influencing the crude odds ratios (ORs) in bivariable logistic
      regression by more than 5%. RESULTS: One in eight ICHs was OAC-associated (n =
      132). Of these, 50% had therapeutic INR (2.0-3.0), 7% had INR <2.0 and 43% had
      high INR (>3.0) on admission. Patients on OAC were older (median 76 vs. 66 years;
      P < 0.001) with more severe symptoms (median National Institutes of Health Stroke
      Scale 14 vs. 10; P < 0.001) and larger hematomas (median 11.4 vs. 9.7 ml; P <
      0.001) on admission than patients not on OAC. After adjustment for confounders, 3
      month mortality in the whole cohort was associated with higher baseline INR (OR
      1.06; CI 1.03-1.09 per 0.1 increment). Mortality was higher with both therapeutic
      (51% at 3 months; OR 3.59; CI 1.50-8.60) and high (61%; OR 5.26; CI 1.94-14.27)
      INR values compared with non-OAC-associated ICH (29%). CONCLUSIONS: Patients with
      OAC-associated ICH had more severe strokes and higher mortality compared with
      patients with ICH not related to OAC. Higher baseline INR was associated with
      increased 3-month mortality.

PMID- 24447729
TI  - Immune response of Chilo suppressalis Walker (Lepidoptera: Crambidae) larvae to
      different entomopathogenic fungi.
AB  - The current study reports mortality and effects on cellular immune response of
      several entomopathogenic fungi including isoleates BB1, BB2 and BB3 of Beauveria
      bassiana, Metarhizium anisopliae, Isaria fumosoroseus and Lecanicilium lecanii
      against larvae of Chilo suppressalis. Prohemocytes, granulocytes, plasmatocytes
      and oenocytoids were identified as the main circulating hemocytes in the
      hemolymph of larvae using Giemsa staining solution. Entomopathogenic fungi caused
      differential mortality on larvae: BB1, BB3, M. anisopliae lead to the highest
      mortality on larvae and L. lecanii caused the lowest mortality. The highest
      numbers of total hemocytes were observed 3 h post-injection of B. bassiana
      isolates and 6 h for the other treatments. The highest numbers of plasmatocytes
      were observed 3 h post-injection of BB1 and Tween 80, whereas BB2, BB3, M.
      anisopliae, I. fumosoroseus and L. lecani caused plasmatocyte increase 6 h post
      injection. Similar results were obtained in case of granulocytes but only Tween
      80 showed the highest number of hemocytes 3 h post-injection. The highest numbers
      of nodules were found at various time intervals after injection of fungal
      isolates and latex bead. The highest activities of phenoloxidase were observed 12
      h post-injection by BbB1, BbB3, M. anisopliae and latex bead; 3-6 h post
      injection by BbB2, 6 h post-injection by I. fumosoroseus and 3-6 h post-injection
      by L. lecanii. Our data demonstrate the possibility of utilizing different fungal
      extracts in the field to help reduce the risk of resistance evolution in C.
      suppressalis and encourage experimentations aimed to increase the number of
      biological control agent for insect pests such as the striped rice stem borer C.
      suppressalis.

PMID- 24447728
TI  - Acute myeloid leukemia after myelodysplastic syndrome and failure of therapy with
      hypomethylating agents: an emerging entity with a poor prognosis.
AB  - We assessed the outcomes of 63 patients with acute myeloid leukemia (AML) arising
      from myelodysplastic syndrome (MDS) after hypomethylating agent failure. Their
      median age was 63 years. All 63 patients had received >= 1 salvage regimens for
      AML, and 35 patients (55%) had received >= 2. Of the 31 patients (49%) who had
      received high-dose cytarabine (HDAC) at first relapse, 2 (6%) achieved complete
      remission (CR) and 4 (13%) CR with incomplete platelet recovery (overall response
      rate, 19%). Of the 32 patients (51%) who had received other treatments, including
      investigational agents, 4 (12%) achieved CR and 4 (12%) CR with incomplete
      platelet recovery (overall response rate, 24%). The median response duration was
      20 weeks. With a median follow-up of 42 months from the AML diagnosis, the median
      survival (21 weeks) was similar between the 2 groups. The 1- and 2-year survival
      rate was 19% and 8%, respectively. Multivariate analysis identified low albumin,
      HDAC treatment, and platelet count < 50 * 10(9)/L as independent adverse factors
      for CR and a platelet count < 50 * 10(9)/L and age > 65 years as independent
      adverse factors for survival. Thus, the outcome of AML evolving from MDS after
      hypomethylating agent failure is poor and not improved with HDAC. Novel therapies
      directed toward this emerging entity are urgently needed.

PMID- 24447730
TI  - Oesophageal injuries: Position paper, WSES, 2013.
AB  - The oesophagus is a difficult challenge for the surgeon because of its lack of
      serosal covering, the tenuous, segmental blood supply and the common delay in the
      diagnosis of injury. Early diagnosis is the key to successful management. Recent
      introduction of newer, minimally invasive techniques have provided management
      alternatives for both the normal and the diseased organ that is injured with both
      early and delayed diagnosis. 

PMID- 24447731
TI  - Brugada phenocopy or Brugada ECG pattern in patients characterized by early
      repolarization pattern and additional arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 24447732
TI  - Coronary flow reserve is associated with tissue ischemia and is an additive
      predictor of intensive care unit mortality to traditional risk scores in septic
      shock.
AB  - BACKGROUND: Reduced coronary velocity flow reserve (CFR) is associated with poor
      outcome in patients with cardiovascular disease. We investigated whether CFR is
      associated with tissue ischemia and acidosis, impaired myocardial deformation and
      adverse outcome in patients with septic shock. METHODS: In 70 mechanically
      ventilated patients with septic shock, we examined: a) S' and E' mitral annular
      velocities using tissue Doppler imaging (TDI), b) CFR of the left anterior
      descending artery after adenosine infusion using transesophageal Doppler
      echocardiography and c) lactate, pyruvate and glycerol in tissue by means of a
      microdialysis (MD) catheter inserted into the subcutaneous adipose tissue as
      markers of tissue ischemia and acidosis. SOFA and APACHE II prognostic scores and
      mortality in the intensive care unit (ICU) were recorded. RESULTS: Reduced CFR,
      S' and E' as well as increased E/E' correlated with increased SOFA, APACHE II and
      MD lactate to pyruvate ratio (p<0.05 for all correlations). Impaired TDI markers
      also correlated with increased MD glycerol (p<0.05). Reduced CFR correlated with
      decreased E' (p<0.05). CFR was 1.8 +/- 0.42 in non-survivors (n=34) versus 2.08
      +/- 0.44 in survivors (p=0.007). A CFR<1.90 predicted mortality with sensitivity
      of 70% and specificity of 69% (area under the curve 77%; p=0.003). CFR had an
      additive value to APACHE (chi-square change: 4.358, p=0.03) and SOFA (chi-square
      change: 3.692, p=0.04) for the prediction of mortality. CONCLUSION: Tissue
      ischemia and acidosis is a common pathophysiological link between decreased CFR
      and impaired LV myocardial deformation in septic shock. CFR is an additive
      predictor of ICU mortality to traditional risk scores in septic shock.

PMID- 24447733
TI  - Bioresorbable vascular scaffold implantation for treatment of recurrent in-stent
      restenosis: insights from optical coherence tomography.

PMID- 24447734
TI  - Renal denervation: the potential causes of non-response.

PMID- 24447735
TI  - Circulating serum levels of growth differentiation factor-15 and neuregulin-1 in
      patients with paroxysmal non-valvular atrial fibrillation.

PMID- 24447736
TI  - Saline vs contrast infusion during optical coherence tomography imaging of
      peripheral percutaneous intervention.

PMID- 24447737
TI  - Stress status and ventricular fibrillation in long QT syndrome.

PMID- 24447738
TI  - QTc interval prolongation with high dose energy drink consumption in a healthy
      volunteer.

PMID- 24447739
TI  - Congenital heart disease may hurt men more than women in job participation.

PMID- 24447740
TI  - Relationship between repolarization heterogeneity and abnormal myocardial
      mechanics.

PMID- 24447741
TI  - Morphology of the heart associated with its function as conceived by ancient
      Greeks.
AB  - According to their writings, ancient Greek physicians had explored the anatomy of
      the heart. Although pre-Hippocratic medicine, which relied on religion and
      mysticism, has nothing more to present than implausible theories and
      speculations, younger physicians thanks to their animal dissections were able to
      depict the heart with detail. Hippocratic "On the Heart", Aristotle's,
      Herophilus', Erasistratus' and Galen's writings provide us with the necessary
      data to take a look at the anatomy of the heart as it was described back then.
      Despite of some confusing passages in their writings and some erroneous notions,
      the heart was described with relative accuracy. In the years after antiquity and
      in the Middle Age the only information about the anatomy of the heart could be
      derived from the ancient Greek works and only anatomists of the Renaissance
      managed to displace them. In this paper we present the knowledge of all known
      ancient Greek physicians about the heart, with emphasis on its anatomy.

PMID- 24447742
TI  - Aortic excess pressure and arterial stiffness in subjects with subclinical white
      matter lesions.

PMID- 24447743
TI  - Myocardial infarction secondary to 5-fluorouracil: not an absolute
      contraindication to rechallenge?

PMID- 24447744
TI  - Comparison of non-cardiac findings by a cardiologist with those by a radiologist
      team in 320 slice CT heart images.

PMID- 24447745
TI  - Asymmetric dimethylarginine is not associated with subendocardial viability ratio
      in Rheumatoid Arthritis.

PMID- 24447746
TI  - Impact of pulmonary artery catheter on outcome in patients with acute heart
      failure syndromes with hypotension or receiving inotropes: from the ATTEND
      Registry.
AB  - BACKGROUND: Randomized controlled trials concerning pulmonary artery catheters
      (PACs) use have yielded little evidence of their beneficial effects on survival.
      This study aimed to evaluate the association between PACs and in-hospital
      mortality in patients with acute heart failure syndromes (AHFS). METHODS: The
      Acute Decompensated Heart Failure Syndromes (ATTEND) Registry is a prospective,
      observational, multicenter cohort study performed in Japan, since April 2007. We
      analyzed data from the ATTEND Registry and evaluated the effectiveness of PAC in
      AHFS treatment using propensity score-matching and the Cox proportional hazards
      model. RESULTS: Final follow-up examinations of the 4842 patients were conducted
      in December 2012. During the study period, 813 patients (16.8%) were managed with
      PACs, of which 502 patients (PAC group) were propensity score-matched with 502
      controls (Control group). Of the 1004 score-matched patients, 22 (4.4%) patients
      from the Control group and 7 (1.4%) from the PAC group died. The risk of all
      cause death was lower in the PAC group than that in the Control group [hazard
      ratio (HR), 0.3; 95% confidence interval (CI), 0.13-0.70; p=0.006]. PAC-guided
      therapy decreased all-cause mortality in patients with lower systolic blood
      pressure (SBP <= 100 mm Hg; HR, 0.09; 95% CI, 0.01-0.70; p=0.021) or inotropic
      therapy (HR, 0.22; 95% CI, 0.08-0.57; p=0.002). CONCLUSIONS: This study revealed
      that appropriate PAC use effectively decreases in-hospital mortality in AHFS
      patients, particularly those with lower SBP or receiving inotropic therapy,
      suggesting that real-world PAC use could improve AHFS management.

PMID- 24447747
TI  - Tachycardia mediated cardiomyopathy: pathophysiology, mechanisms, clinical
      features and management.
AB  - Tachycardia mediated cardiomyopathy (TMC) is a reversible form of dilated
      cardiomyopathy that can occur with most supraventricular and ventricular
      arrhythmias. Despite the plethora of literature describing this entity in animal
      models, as well as humans, it remains poorly understood. Over the last decade,
      new etiologies of TMC, such as frequent premature ventricular complexes in normal
      hearts, have been identified. Recent advances in catheter-based ablation
      therapies, particularly for atrial fibrillation and ventricular arrhythmias, have
      added a new dimension to the treatment of this condition. This review describes
      the pathophysiology, proposed mechanisms, clinical features and management in
      various arrhythmic conditions. 

PMID- 24447748
TI  - Arrhythmogenic right ventricular cardiomyopathy--an update.

PMID- 24447749
TI  - Simple reaction time and the risk of cardiovascular mortality.

PMID- 24447750
TI  - Tailoring of antiplatelet therapy in a patient with bleeding and PCI: a double
      edged sword?

PMID- 24447751
TI  - Prevalence, clinical profile and 3-year survival of acute myocardial infarction
      patients with and without obstructive coronary lesions: the FAST-MI 2005
      registry.

PMID- 24447752
TI  - Renal function estimation and one-year mortality in elderly patients with non-ST
      segment elevation acute coronary syndromes.

PMID- 24447753
TI  - Haemodynamic measurements before and after angioplasty in post-ablation pulmonary
      vein stenosis.

PMID- 24447754
TI  - Clinical impact of fractional flow reserve in a real-world cohort of patients.

PMID- 24447755
TI  - Transient right ventricular dysfunction consequent to acute pulmonary embolism as
      a pathophysiological model of Takotsubo syndrome.

PMID- 24447756
TI  - Unilateral renal denervation: is the 'fragmentary' procedure 'disabled'?

PMID- 24447757
TI  - 3D heart model guides complex stent angioplasty of pulmonary venous baffle
      obstruction in a Mustard repair of D-TGA.

PMID- 24447758
TI  - Absorb bioresorbable scaffold implantation for the treatment of an ostial chronic
      total occlusion.

PMID- 24447759
TI  - The risk of infection with new oral anticoagulants: a meta-analysis.

PMID- 24447760
TI  - Impact of therapeutic hypothermia on coronary flow.

PMID- 24447761
TI  - Minimal and deep sedation during ablation of ventricular tachycardia.
AB  - BACKGROUND: Catheter ablation is a curative treatment option for ventricular
      premature contractions (VPC) and ventricular tachycardia (VT). Procedures require
      different sedation levels, depending on duration, ablation approach and patient
      characteristics. The aim of our study was to evaluate feasibility of minimal and
      deep sedation for ablation of VPC/VT. METHODS: Patients underwent catheter
      ablation of VPC/VT under minimal or deep sedation. Events of hypotension,
      hypoxia, bradycardia, procedural complications and VT inducibility were compared
      between the groups. RESULTS: 120 patients were included. In 42 patients (53.6 +/-
      17.1 years, 47.6% male) ablation was performed under minimal sedation with
      midazolam, and in 78 patients (54.2 +/- 17.5 years, 67.9% male) ablation was
      performed under deep sedation with propofol/midazolam. There were significantly
      fewer patients with idiopathic VT (62.8 vs. 88.1%, p=0.011) in the deep sedation
      group, LVEF was significantly lower (47 +/- 14.4 vs. 53.1 +/- 11.7) and the
      procedure duration was significantly longer (201.9 +/- 85.9 vs. 137.9 +/- 98.7).
      No significant differences in procedural complications or sedation related events
      (hypotension: 0 vs. 3.8%, p=0.2, no hypoxia, no bradycardia) were detected.
      CONCLUSIONS: Minimal sedation and deep sedation are both feasible during VPC/VT
      ablation procedures. Propofol does not increase complications even in a
      collective with pre-existing impairment of LVEF. Adequate monitoring and trained
      personnel should be present.

PMID- 24447762
TI  - Left ventricular hypertrophy in asymptomatic individuals without overt heart
      disease.

PMID- 24447763
TI  - Geometrical characteristics of interventricular electrical delay.

PMID- 24447764
TI  - Rabies in Henan province, China, 2010-2012.

PMID- 24447765
TI  - Nanoindentation experiments for single-layer rectangular graphene films: a
      molecular dynamics study.
AB  - A molecular dynamics study on nanoindentation experiments is carried out for some
      single-layer rectangular graphene films with four edges clamped. Typical load
      displacement curves are obtained, and the effects of various factors including
      indenter radii, loading speeds, and aspect ratios of the graphene film on the
      simulation results are discussed. A formula describing the relationship between
      the load and indentation depth is obtained according to the molecular dynamics
      simulation results. Young's modulus and the strength of the single-layer graphene
      film are measured as about 1.0 TPa and 200 GPa, respectively. It is found that
      the graphene film ruptured in the central point at a critical indentation depth.
      The deformation mechanisms and dislocation activities are discussed in detail
      during the loading-unloading-reloading process. It is observed from the
      simulation results that once the loading speed is larger than the critical
      loading speed, the maximum force exerted on the graphene film increases and the
      critical indentation depth decreases with the increase of the loading speed. 

PMID- 24447766
TI  - Prevalence of antibiotic resistance in lactic acid bacteria isolated from the
      faeces of broiler chicken in Malaysia.
AB  - BACKGROUND: Probiotics are commonly used as feed additive to substitute
      antibiotic as growth promoter in animal farming. Probiotic consists of lactic
      acid bacteria (LAB), which enhance the growth and health of the animal. Probiotic
      also have higher possibility to become pathogenic bacteria that may carry
      antibiotic resistant gene that can be transmitted to other LAB species. The aim
      of this study was to identify the LAB species in the faeces of broiler chicken
      and to determine the prevalence of antibiotic resistant in LAB of broiler
      chicken. METHODS: Sixty faeces samples were collected from wet markets located in
      Klang Valley of Malaysia for the isolation of LAB using de-Mann Rogosa Sharpe
      medium. Thirteen species of LAB were obtained in this study and the
      identification of LAB was performed by using API test kit on the basis of
      carbohydrate fermentation profile. Antibiotic susceptibility assay was then
      carried out to determine the prevalence of LAB antibiotic resistance. RESULTS:
      Lactococcus lactis subsp lactis was found in nine out of sixty faecal samples.
      Lactobacillus paracasei was the second common LAB species isolated from chicken
      faecal. No significant difference (P > 0.05) was found between the occurrence of
      Lactobacillus brevis, Lactobacillus curvatus, Lactobacillus plantarum,
      Leuconostoc lactis mesenteroides subsp mesenteroides/dectranium and Pediococcus
      pentosaceus isolated from 5 different locations. Most of the isolated LAB was
      resistant to antibiotic and high variability of the antibiotic resistance was
      observed among the LAB against 15 types of antibiotics. Penicillin, amoxicillin,
      chloramphenicol, and ampicillin had significant higher (P< 0.05) inhibitory zone
      than nalidixic acid, gentamycin, sulphamethoxazole, kanamycin, and streptomycin.
      CONCLUSIONS: Many species of LAB were isolated from the faecal samples of broiler
      chicken that resistance to the common antibiotics used in the farm. The
      development of resistant against antibiotics in LAB can be attributed to the long
      term exposure of antibiotic as growth promoter and therapeutic agents. Thus, it
      is essential to advise farmer the safety measure of antibiotic application in
      animal farming. Additionally, the supplementation of probiotic in animal feeding
      also needs more attention and close monitoring.

PMID- 24447767
TI  - Development of SNP-genotyping arrays in two shellfish species.
AB  - Use of SNPs has been favoured due to their abundance in plant and animal genomes,
      accompanied by the falling cost and rising throughput capacity for detection and
      genotyping. Here, we present in vitro (obtained from targeted sequencing) and in
      silico discovery of SNPs, and the design of medium-throughput genotyping arrays
      for two oyster species, the Pacific oyster, Crassostrea gigas, and European flat
      oyster, Ostrea edulis. Two sets of 384 SNP markers were designed for two Illumina
      GoldenGate arrays and genotyped on more than 1000 samples for each species. In
      each case, oyster samples were obtained from wild and selected populations and
      from three-generation families segregating for traits of interest in aquaculture.
      The rate of successfully genotyped polymorphic SNPs was about 60% for each
      species. Effects of SNP origin and quality on genotyping success (Illumina
      functionality Score) were analysed and compared with other model and nonmodel
      species. Furthermore, a simulation was made based on a subset of the C. gigas SNP
      array with a minor allele frequency of 0.3 and typical crosses used in shellfish
      hatcheries. This simulation indicated that at least 150 markers were needed to
      perform an accurate parental assignment. Such panels might provide valuable tools
      to improve our understanding of the connectivity between wild (and selected)
      populations and could contribute to future selective breeding programmes.

PMID- 24447768
TI  - Cross-linguistic variation in the neurophysiological response to semantic
      processing: evidence from anomalies at the borderline of awareness.
AB  - The N400 event-related brain potential (ERP) has played a major role in the
      examination of how the human brain processes meaning. For current theories of the
      N400, classes of semantic inconsistencies which do not elicit N400 effects have
      proven particularly influential. Semantic anomalies that are difficult to detect
      are a case in point ("borderline anomalies", e.g. "After an air crash, where
      should the survivors be buried?"), engendering a late positive ERP response but
      no N400 effect in English (Sanford, Leuthold, Bohan, & Sanford, 2011). In three
      auditory ERP experiments, we demonstrate that this result is subject to cross
      linguistic variation. In a German version of Sanford and colleagues' experiment
      (Experiment 1), detected borderline anomalies elicited both N400 and late
      positivity effects compared to control stimuli or to missed borderline anomalies.
      Classic easy-to-detect semantic (non-borderline) anomalies showed the same
      pattern as in English (N400 plus late positivity). The cross-linguistic
      difference in the response to borderline anomalies was replicated in two
      additional studies with a slightly modified task (Experiment 2a: German;
      Experiment 2b: English), with a reliable LANGUAGE*ANOMALY interaction for the
      borderline anomalies confirming that the N400 effect is subject to systematic
      cross-linguistic variation. We argue that this variation results from differences
      in the language-specific default weighting of top-down and bottom-up information,
      concluding that N400 amplitude reflects the interaction between the two
      information sources in the form-to-meaning mapping.

PMID- 24447769
TI  - Dynamic stimuli demonstrate a categorical representation of facial expression in
      the amygdala.
AB  - Face-selective regions in the amygdala and posterior superior temporal sulcus
      (pSTS) are strongly implicated in the processing of transient facial signals,
      such as expression. Here, we measured neural responses in participants while they
      viewed dynamic changes in facial expression. Our aim was to explore how facial
      expression is represented in different face-selective regions. Short movies were
      generated by morphing between faces posing a neutral expression and a
      prototypical expression of a basic emotion (either anger, disgust, fear,
      happiness or sadness). These dynamic stimuli were presented in block design in
      the following four stimulus conditions: (1) same-expression change, same
      identity, (2) same-expression change, different-identity, (3) different
      expression change, same-identity, and (4) different-expression change, different
      identity. So, within a same-expression change condition the movies would show the
      same change in expression whereas in the different-expression change conditions
      each movie would have a different change in expression. Facial identity remained
      constant during each movie but in the different identity conditions the facial
      identity varied between each movie in a block. The amygdala, but not the
      posterior STS, demonstrated a greater response to blocks in which each movie
      morphed from neutral to a different emotion category compared to blocks in which
      each movie morphed to the same emotion category. Neural adaptation in the
      amygdala was not affected by changes in facial identity. These results are
      consistent with a role of the amygdala in category-based representation of facial
      expressions of emotion. 

PMID- 24447770
TI  - Hemoglobin adducts as biomarkers of estrogen homeostasis: elevation of
      estrogenquinones as a risk factor for developing breast cancer in Taiwanese
      women.
AB  - The aim of this study was to establish a methodology to analyze estrogen quinone
      derived adducts, including 17beta-estradiol-2,3-quinone (E2-2,3-Q) and 17beta
      estradiol-3,4-quinone (E2-3,4-Q), in human hemoglobin (Hb). The methodology was
      then used to measure the levels of these adducts in Hb derived from female breast
      cancer patients (n=143) as well as controls (n=147) in Taiwan. Our result
      confirmed that both E2-2,3-Q- and E2-3,4-Q-derived adducts, including E2-2,3-Q-4
      S-Hb and E2-3,4-Q-2-S-Hb, were detected in all breast cancer patients with median
      levels at 434 (215-1472) and 913 (559-2384) (pmol/g), respectively. Levels of E2
      2,3-Q-4-S-Hb correlated significantly with those of E2-3,4-Q-2-S-Hb (r=0.622
      0.628, p<0.001). By contrast, median levels of these same estrogen quinone
      derived adducts in healthy controls were 71.8 (35.7-292) and 139 (69.1-453)
      (pmol/g). This translated to ~6-fold increase in mean values of E2-2,3-Q-4-S-Hb
      and E2-3,4-Q-2-S-Hb in breast cancer patients compared to those in the controls
      (p<0.001). Our findings add further support to the theme that cumulative body
      burden of estrogen quinones is an important indicator of breast cancer risk. We
      hypothesize that combination of genetic events and environmental factors may
      modulate estrogen homeostasis and enhance the production of estrogen quinones
      which lead to subsequent generation of pro-mutagenic DNA lesions in breast cancer
      patients.

PMID- 24447771
TI  - Melioidosis caused by Burkholderia pseudomallei in drinking water, Thailand,
      2012.
AB  - We identified 10 patients in Thailand with culture-confirmed melioidosis who had
      Burkholderia pseudomallei isolated from their drinking water. The multilocus
      sequence type of B. pseudomallei from clinical specimens and water samples were
      identical for 2 patients. This finding suggests that drinking water is a
      preventable source of B. pseudomallei infection. 

PMID- 24447772
TI  - Effects of pulsed fluid lens capsule washing following phacoemulsification on
      lens epithelial cells and posterior capsule opacification formation ex vivo.
AB  - BACKGROUND: The aim of the study was to evaluate ex vivo the effects of using a
      custom tip to direct a pulsed stream of fluid to remove residual lens epithelial
      cells (LECs) and reduce posterior capsule opacification (PCO) formation following
      phacoemulsification. METHODS: Twenty-four canine cadaver eyes were assigned to
      one of three treatment groups. Six eyes (Control Group) had standard
      phacoemulsification only, nine eyes (Group 1) had standard phacoemulsification
      followed by capsular washing using intermediate settings (power = 40%, pulses per
      second [PPS] = 50, 30 s washing per capsule hemisphere), and nine eyes (Group 2)
      had standard phacoemulsification followed by aggressive capsular washing (power =
      60%, PPS = 50, 60 s washing per capsule hemisphere). RESULTS: Control lens
      capsules had diffuse LECs remaining following standard phacoemulsification and
      complete ex vivo PCO formation (confluent LECs on the posterior capsule) within 4
      +/- 2 days (range 2-8 days). Group 1 lens capsules had focal, equatorial LEC
      clusters remaining following treatment, and complete PCO formation within 9 +/- 2
      days (range 5-11 days). Group 2 lens capsules had little to no LECs observed
      following treatment; 5 of 9 capsules had complete PCO formation within 13 +/- 2
      days (range 9-14 days), and 4 of 9 capsules had no PCO formation by 24 days post
      treatment. CONCLUSIONS: Pulsed fluid lens capsule washing is capable of removing
      LECs and delaying PCO formation in canine eyes following phacoemulsification ex
      vivo. Use of more aggressive capsular washing settings resulted in more effective
      LEC removal and subsequent delay of ex vivo PCO.

PMID- 24447773
TI  - A one-pot three-component synthesis of 4,6-diarylpyrimidin-2(1H)-ones (DAPMs)
      using atomized sodium in THF under sonic condition.
AB  - A simple and an efficient procedure for the synthesis of 4,6-diarylpyrimidin
      2(1H)-ones using atomized sodium/THF via a one-pot three-component Biginelli-like
      cyclocondensation of an aldehyde, a methyl ketone and urea under ultrasonic
      condition is developed. The method is mild and inexpensive; yields are high and
      the reactions go to completion within 10-15 min.

PMID- 24447774
TI  - Primitive intrapericardial teratoma associated with yolk sac tumour.
AB  - An intrapericardial vacuolated mass compressing and displacing the heart was
      diagnosed by echocardiography in a foetus of 22 weeks gestation. The birth was
      induced for early signs of foetal distress at 29 weeks and, after two initial
      pericardial evacuation procedures, the tumour was resected radically 7 days after
      birth at a weight of 1.55 kg. Mass histology showed teratoma associated with yolk
      sac tumour. We comment on the overall approach adopted after foetal diagnosis and
      the histopathological features of the tumour, and try to draw conclusions on
      patient outcome data.

PMID- 24447775
TI  - Weight loss composition is one-fourth fat-free mass: a critical review and
      critique of this widely cited rule.
AB  - Maximizing fat loss while preserving lean tissue mass and function is a central
      goal of modern obesity treatments. A widely cited rule guiding expected loss of
      lean tissue as fat-free mass (FFM) states that approximately one-fourth of weight
      loss will be FFM (i.e. DeltaFFM/DeltaWeight = ~0.25), with the remaining three
      fourths being fat mass. This review examines the dynamic relationships between
      FFM, fat mass and weight changes that follow induction of negative energy balance
      with hypocaloric dieting and/or exercise. Historical developments in the field
      are traced with the 'Quarter FFM Rule' used as a framework to examine evolving
      concepts on obesity tissue, excess weight and what is often cited as 'Forbes'
      Rule'. Temporal effects in the fractional contribution of FFM to changes in body
      weight are examined as are lean tissue moderating effects such as ageing,
      inactivity and exercise that frequently accompany structured low-calorie diet
      weight loss protocols. Losses of lean tissue with dieting typically tend to be
      small, raising questions about study design, power and applied measurement method
      reliability. Our review elicits important questions related to the fractional
      loss of lean tissues with dieting and provides a foundation for future research
      on this topic. 

PMID- 24447777
TI  - Is rheumatoid arthritis a B-cell haematological disease with a predilection for
      the joints? Following the B cell thread to its logical conclusion.
AB  - B-cell depleting therapy (BCDT) is effective in suppressing synovitis and
      erosions in rheumatoid arthritis suggesting that a cell of the B-lymphocyte
      lineage is critical in the pathogenesis of this disease. Non-Hodgkins lymphoma
      (NHL) also responds to BCDT but multiple myeloma (MM), does not as cells have
      differentiated beyond the CD20-bearing stage. However, there are similarities
      between B-NHL, MM and RA that suggest all 3 conditions could be initiated and
      perpetuated by the same cellular players. Numerous plasma cells and B cells are
      present within rheumatoid synovial membrane, and subarticular bone where they
      contribute to osteitis. On MRI scans this appears as bone oedema, which has been
      demonstrated to precede the development of bone erosions. Plasma cell clonality
      has been detected within RA synovial membrane and bone marrow. It is proposed
      that RA could represent a "forme fruste" of a B cell neoplastic condition, with
      production of autoantibodies that target a self-antigen within the joint. The
      activation of rheumatoid bone osteoclasts by anticitrullinated protein antibodies
      supports this theory. The erosions of RA would have parallels with the lytic
      lesions of MM but autoantigen targeting dictates that erosions occur at joint
      margins. This theory is discussed from rheumatologic and haematologic
      perspectives. 

PMID- 24447776
TI  - Aqueous extract of dioscorea opposita thunb. normalizes the hypertension in 2K1C
      hypertensive rats.
AB  - BACKGROUND: Dioscorea opposita Thunb. (Huai Shan Yao, DOT), a common staple food
      in China, has been used for more than 2000 years in traditional Chinese medicine
      (TCM) to treat different systemic diseases including hypertension. The objective
      of this study was to investigate the possible antihypertensive effects of the
      aqueous extract of (DOT) in renovascular hypertensive rats as well as the
      mechanism in reducing blood pressure. METHODS: The two-kidney one-clip (2K1C)
      Goldblatt model of renovascular hypertension was used in Wistar rats. Rats with
      captopril, low-dose DOT and high-dose DOT treated 2K1C groups for 6 weeks. The
      blood pressure, cardiac mass index (heart weight/body weight), plasma level of
      angiotensin-II (Ang-II), endothelin-1(ET-1), superoxide dismutase (SOD) and
      malondialdehyde (MDA) were evaluated. RESULTS: DOT significantly reduced mean
      systolic and diastolic blood pressure after treatment. DOT also significantly
      increased plasma SOD activity but decreased plasma MDA concentration. Renal
      function was improved with captopril and DOT. DOT reduced plasma Ang-II activity
      and plasma ET concentration. They couldalso significantly reduce the left
      ventricular hypertrophy and cardiac mass index. CONCLUSIONS: Our results suggest
      that DOT may have an antihypertensive effect on hypertension by inhibit ET
      converting enzyme and antioxidant activity, which warrant further exploration.

PMID- 24447778
TI  - BMC Medicine editorial board members on open access publishing.
AB  - In recognition of Open Access week (21st-27th October 2013), we asked some BMC
      Medicine Editorial Board Members to share their views and experiences on open
      access publishing. In this short video, they highlight the benefits of visibility
      and dissemination of their research, and discuss the future directions for this
      model of publishing. 

PMID- 24447779
TI  - ATG brands and DSA.

PMID- 24447780
TI  - Poorly processed reusable surface disinfection tissue dispensers may be a source
      of infection.
AB  - BACKGROUND: Reusable surface disinfectant tissue dispensers are used in hospitals
      in many countries because they allow immediate access to pre-soaked tissues for
      targeted surface decontamination. On the other hand disinfectant solutions with
      some active ingredients may get contaminated and cause outbreaks. We determined
      the frequency of contaminated surface disinfectant solutions in reusable
      dispensers and the ability of isolates to multiply in different formulations.
      METHODS: Reusable tissue dispensers with different surface disinfectants were
      randomly collected from healthcare facilities. Solutions were investigated for
      bacterial contamination. The efficacy of two surface disinfectants was determined
      in suspension tests against two isolated species directly from a contaminated
      solution or after 5 passages without selection pressure in triplicate. Freshly
      prepared use solutions were contaminated to determine survival of isolates.
      RESULTS: 66 dispensers containing disinfectant solutions with surface-active
      ingredients were collected in 15 healthcare facilities. 28 dispensers from nine
      healthcare facilities were contaminated with approximately 107 cells per mL of
      Achromobacter species 3 (9 hospitals), Achromobacter xylosoxidans or Serratia
      marcescens (1 hospital each). In none of the hospitals dispenser processing had
      been adequately performed. Isolates regained susceptibility to the disinfectants
      after five passages without selection pressure but were still able to multiply in
      different formulations from different manufacturers at room temperature within 7
      days. CONCLUSIONS: Neglecting adequate processing of surface disinfectant
      dispensers has contributed to frequent and heavy contamination of use-solutions
      based on surface active ingredients. Tissue dispenser processing should be taken
      seriously in clinical practice.

PMID- 24447781
TI  - Peste des petits ruminants virus, Mauritania.

PMID- 24447783
TI  - Age-related vascular gene expression profiling in mice.
AB  - Increasing age involves a number of detrimental changes in the cardiovascular
      system and particularly on the large arteries. It deteriorates vascular integrity
      and leads to increased vascular stiffness entailing hypertension with increased
      cardiovascular morbidity and mortality. The consequences of continuous oxidative
      stress and damages to biomolecules include altered gene expression, genomic
      instability, mutations, loss of cell division and cellular responses to increased
      stress. Many studies have been performed in aged C57BL/6 mice; however, analyses
      of the age-related changes that occur at a gene expression level and
      transcriptional profile in vascular tissue have not been elucidated in depth. To
      determine the changes of the vascular transcriptome, we conducted gene expression
      microarray experiments on aortas of adult and old mice, in which age-related
      vascular dysfunction was confirmed by increased stiffness and associated systolic
      hypertension. Our results highlight differentially expressed genes
      overrepresented in Gene Ontology categories. Molecular interaction and reaction
      pathways involved in vascular functions and disease, within the transforming
      growth factor-beta (TGF-beta) pathway, the renin-angiotensin system and the
      detoxification systems are displayed. Our results provide insight to an altered
      gene expression profile related to age, thus offering useful clues to counteract
      or prevent vascular aging and its detrimental consequences. 

PMID- 24447784
TI  - Stress and aging at the nuclear gateway.
AB  - The nuclear pore complex (NPC) is a massive molecular machine embedded in the
      nuclear envelope and controlling traffic into and out of the cell nucleus. Here,
      we describe some of the outstanding research questions concerning the NPC, its
      assembly and functions. We also discuss recent findings that link the NPC and its
      immediate surroundings to the process of cellular aging. Scaffold and barrier
      nucleoporins are two major types of protein building blocks that make up the NPC.
      Surprisingly, these two groups of nucleoporins differ dramatically in their
      turnover rates. Recent work identifies some of the scaffold nucleoporins as the
      most extremely long-lived proteins in rat brain. Some of the consequences of
      these findings and new open questions arising from them are discussed. We also
      consider the evidence for a perturbed permeability barrier in nuclei from old
      cells and the alteration of nuclear transport pathways under stress conditions.
      Finally, we describe the connection between premature aging syndromes and the
      nuclear lamina, a filamentous protein network which underlies the nuclear
      envelope. 

PMID- 24447786
TI  - Retinal oxygen metabolism in exudative age-related macular degeneration.
AB  - PURPOSE: To determine whether retinal vessel oxygen saturation in patients with
      exudative age-related macular degeneration (AMD) is different from that of a
      healthy population. METHODS: Oxygen saturation was measured in retinal arterioles
      and venules in 46 eyes of 46 treatment-naive exudative AMD patients and 120 eyes
      of 120 healthy controls. Simple and multiple linear regression analyses were used
      to compare the two study groups. RESULTS: Oxygen saturation in retinal venules
      increases with age in patients with exudative AMD (0.45 +/- 0.19% per year; p =
      0.026), while it decreases with age in healthy individuals (-0.13 +/- 0.03% per
      year; p = 0.0002). The slopes are statistically different (ANCOVA; p = 0.0003).
      The reverse is true for the arteriovenous difference in oxygen saturation, which
      decreases with age in AMD patients (-0.29 +/- 0.16% per year; p = 0.065) and
      increases in healthy individuals (0.12 +/- 0.03% per year; p < 0.0001). At age 80
      years, AMD patients have 2.7 percentage points higher venous oxygen saturation
      than healthy persons and 4.2 percentage points less arteriovenous difference.
      CONCLUSIONS: The data suggest that retinal oxygen metabolism may be altered in
      exudative AMD. The arteriovenous difference is smaller in exudative AMD than in a
      healthy cohort, consistent with reduced oxygen extraction by retinal vessels in
      AMD patients. Further studies are needed to fully understand the role of retinal
      oxygen metabolism in the pathophysiology of exudative AMD.

PMID- 24447788
TI  - Formulation parameters of crystalline nanosuspensions on spray drying processing:
      a DoE approach.
AB  - Nanocrystalline suspensions offer a promising approach to improve dissolution of
      BCS class II/IV compounds. Spray drying was utilized as a downstream process to
      improve the physical and chemical stability of dried nanocrystals. The effect of
      nanocrystalline suspension formulation variables on spray-drying processing was
      investigated. Naproxen and indomethacin nanocrystalline formulations were
      formulated with either Dowfax 2A1 (small molecule) or HPMC E15 (high molecular
      weight polymer) and spray drying was performed. A DoE approach was utilized to
      understand the effect of critical formulation variables, i.e. type of stabilizer,
      type of drug, ratio of drug-to-stabilizer and drug concentration. The powders
      were analyzed for particle size, moisture content, powder X-ray diffraction and
      dissolution. A dialysis sac adapter for USP apparatus II was developed which
      provided good discrimination between aggregated and non-aggregated formulations.
      Nanocrystal aggregation was dependent on the drug-to-stabilizer ratio. The glass
      transition temperature and the charge effect played a dominant role on spray
      dried powder yield. Those formulations with low drug-to-excipient ratios were
      less aggregating and showed faster dissolution compared to those formulations
      with high drug-to-excipient ratios. All stable (less aggregated) formulations
      were subjected to accelerated storage stability testing. The Flory-Huggins
      interaction parameter (between drug and excipients) correlated with the spray
      dried nanocrystal formulations stability. 

PMID- 24447790
TI  - Sequential sub-passage decreases the differentiation potential of canine adipose
      derived mesenchymal stem cells.
AB  - Adipose-derived mesenchymal stem cells (AD-MSCs) are abundant in adipose tissue
      from animals of all ages, are easily isolated, can differentiate into multi
      lineage cells, and have a clinical application. This promising potential may only
      be achieved if the cells are expanding in a large number while maintaining their
      stemness in sequential passages. In this study, canine AD-MSCs (cAD-MSCs) were
      individually isolated from five dogs and subjected to proliferative culture with
      seven sub-passages. The cells at each sub-passage were characterized for
      properties associated with multipotent MSCs such as proliferation kinetics,
      expression of MSCs-specific surface markers, expression of molecules associated
      with self-renewal and differentiation capabilities into mesodermal lineage cells.
      Proliferation of the cells plateaued at passage 5 by cumulative population
      doubling level, while cell doubling time gradually increased with passage. MSCs
      surface markers (CD44, CD90, and CD105) and molecules (Oct 3/4, Sox-2, Nanog and
      HMGA2) associated with self-renewal were all expressed in the cells between
      passages 1 to 6 by RT-PCR. In addition, the cells at passage 1, 3 or 6 underwent
      adipogenic and chondrogenic differentiation under specific induction conditions.
      However, the level of adipogenic and chondrogenic differentiation was negatively
      correlated with the number of sub-passage. The present study suggests that
      sequential sub-passages affect multipotent properties of cAD-MSCs, which should
      be considered in their therapeutic application in regenerative medicine. 

PMID- 24447791
TI  - Fos and pERK immunoreactivity in spinal cord slices: Comparative analysis of in
      vitro models for testing putative antinociceptive molecules.
AB  - To detect central neuron activation, expression of the transcription factor Fos
      and phosphorylation of the protein kinase ERK (pERK) can be visualized by
      immunocytochemistry. These approaches have been extensively used to quantify the
      activation of nociceptive neurons in the spinal dorsal horn (DH) following
      peripheral stimulation in vivo. Here we propose an alternative and simplified in
      vitro model to investigate Fos and pERK expression based on the stimulation of
      acutely dissected spinal cord slices to mimic acute inflammatory changes in DH.
      Transverse slices were obtained from postnatal (P8-P12) CD1 mice and were treated
      for 5 min with capsaicin (CAP, 2 MUM). CAP induces a strong release of glutamate
      from primary afferent terminals which, in turn, excites spinal DH neurons. Since
      ERK phosphorylation and Fos expression occur following different time frames, two
      distinct protocols were used to detect their activation. Thus, for studying Fos
      immunoreactivity CAP-treated slices were left for 3h in Krebs solution after
      stimulation. Instead, for studying pERK immunoreactivity slices were maintained
      in Krebs solution for only 15 min after stimulation. Both Fos and pERK were
      significantly up-regulated following CAP challenge. To validate our model we
      tested the efficacy of octreotide (OCT, 1 MUM) in preventing the CAP effect on
      Fos and pERK expression. OCT is a synthetic antinociceptive analog of
      somatostatin, one of the neuropeptides involved in the negative modulation of
      pain signals in DH. After CAP, OCT reduced the response to both Fos and pERK. Our
      data validate the use of Fos and pERK immunoreactivity in vitro to investigate
      the activation of spinal nociceptive pathways and testing potentially
      antinociceptive molecules.

PMID- 24447792
TI  - Fatal systemic morbillivirus infection in bottlenose dolphin, canary islands,
      Spain.
AB  - A systemic morbillivirus infection was diagnosed postmortem in a juvenile
      bottlenose dolphin stranded in the eastern North Atlantic Ocean in 2005. Sequence
      analysis of a conserved fragment of the morbillivirus phosphoprotein gene
      indicated that the virus is closely related to dolphin morbillivirus recently
      reported in striped dolphins in the Mediterranean Sea. 

PMID- 24447793
TI  - A comparative study of the prevalence of domestic violence in women requesting a
      termination of pregnancy and those attending the antenatal clinic.
AB  - OBJECTIVE: To compare the prevalence of domestic violence (DV) in women
      requesting antenatal care (ANC) and termination of pregnancy (TOP) in North East
      England. DESIGN: This was a cross-sectional comparative prevalence study using
      self-administered questionnaires, with women selected as opportunistic samples
      over a concurrent period. SETTING: The participants were screened anonymously and
      confidentially in the ANC and TOP clinics. SAMPLE: Pregnant women in the first
      trimester requesting a TOP or ANC. METHODS: The participants were screened for a
      history of DV using a modified version of the Abuse Assessment Screening tool.
      MAIN OUTCOME MEASURES: Prevalence of DV between ANC and TOP populations, and any
      differences in the characteristics of the women, such as age, level of education,
      or marital status. We aimed to determine the reasons for requesting a TOP.
      RESULTS: There were 507 respondents, with 233 attending ANC and 274 requesting a
      TOP. Of the ANC population, 219 completed the questionnaire. In the TOP
      population, all the questionnaires were fully or partially completed. Women
      requesting a TOP were six times as likely to suffer physical abuse in the current
      relationship (5.8 versus 0.9%; chi(2) = 10.2 (2); P < 0.05), and were five times
      as likely to suffer emotional abuse (9.9 versus 1.8%; chi(2) = 13.6 (2); P <
      0.0001), than those attending ANC. Of the 274 women requesting a TOP, only ten
      mentioned DV as a contributing factor. CONCLUSIONS: There is a higher prevalence
      of DV in the TOP population than in the ANC population, but very few women stated
      that DV influenced their request for a TOP.

PMID- 24447794
TI  - Partial esophageal transplantation is possible as part of a multivisceral graft.
AB  - We report a case of a 9-year-old female with inflammatory myofibroblastic tumor
      (IMT), which involved the upper retroperitoneum, visceral vessels, stomach and
      distal esophagus. Complete resection of the tumor required a multivisceral (MV)
      transplant. Due to tumor involvement, resection of the distal third of recipient
      esophagus was necessary. Gastrointestinal continuity was subsequently established
      via esophagoesophagostomy to donor esophagus en bloc with a standard MV graft.
      After 1.9 years of follow-up, the patient has no symptoms of dysphagia or reflux.
      This case illustrates the feasibility of including the distal donor esophagus as
      part of an MV graft. 

PMID- 24447795
TI  - Electroacupuncture decreases cognitive impairment and promotes neurogenesis in
      the APP/PS1 transgenic mice.
AB  - BACKGROUND: Alzheimer's disease (AD) is a severe neurodegenerative disease for
      which there is currently no effective treatment. The purpose of this study was to
      investigate whether repeated electroacupuncture (EA) stimulation would improve
      cognitive function and the pathological features of AD in amyloid precursor
      protein (APP)/presenilin 1 (PS1) double transgenic mice. METHODS: Cognitive
      function of APP/PS1 double transgenic mice was assessed using the Morris water
      maze test before and after EA treatment. Levels of amyloid beta-peptide (Abeta)
      deposits in the hippocampus and cortex were evaluated by immunofluorescence,
      western blot and enzyme-linked immunosorbent assay. Expression of brain-derived
      neurotrophic factor (BDNF) was also examined by immunofluorescence and western
      blot. The neurogenesis was labeled by the DNA marker bromodeoxyuridine. RESULTS:
      EA stimulation significantly ameliorated the learning and memory deficits of AD
      mice by shortening escape latency and increasing the time spent in the target
      zone during the probe test. Additionally, decreased Abeta deposits and increased
      BDNF expression and neurogenesis in the hippocampus and cortex of EA-treated AD
      mice were detected. The same change was detected in wild-type mice after EA
      treatment compared with wild-type mice without EA treatment. CONCLUSIONS:
      Repeated EA stimulation may improve cognitive function, attenuate Abeta deposits,
      up-regulate the expression of BDNF and promote neurogenesis in the APP/PS1 double
      transgenic mice. This suggests that EA may be a promising treatment for AD.

PMID- 24447797
TI  - Novel bunyavirus in domestic and captive farmed animals, Minnesota, USA.

PMID- 24447796
TI  - Ecological, biological and social dimensions of dengue vector breeding in five
      urban settings of Latin America: a multi-country study.
AB  - BACKGROUND: Dengue is an increasingly important public health problem in most
      Latin American countries and more cost-effective ways of reducing dengue vector
      densities to prevent transmission are in demand by vector control programs. This
      multi-centre study attempted to identify key factors associated with vector
      breeding and development as a basis for improving targeted intervention
      strategies. METHODS: In each of 5 participant cities in Mexico, Colombia,
      Ecuador, Brazil and Uruguay, 20 clusters were randomly selected by grid sampling
      to incorporate 100 contiguous households, non-residential private buildings
      (businesses) and public spaces. Standardized household surveys, cluster
      background surveys and entomological surveys specifically targeted to obtain
      pupal indices for Aedes aegypti, were conducted in the dry and wet seasons.
      RESULTS: The study clusters included mainly urban low-middle class populations
      with satisfactory infrastructure and -except for Uruguay- favourable climatic
      conditions for dengue vector development. Household knowledge about dengue and
      "dengue mosquitoes" was widespread, mainly through mass media, but there was less
      awareness around interventions to reduce vector densities. Vector production
      (measured through pupal indices) was favoured when water containers were outdoor,
      uncovered, unused (even in Colombia and Ecuador where the large tanks used for
      household water storage and washing were predominantly productive) and 
      particularly during the dry season- rainwater filled. Larval infestation did not
      reflect productive container types. All productive container types, including
      those important in the dry season, were identified by pupal surveys executed
      during the rainy season. CONCLUSIONS: A number of findings are relevant for
      improving vector control: 1) there is a need for complementing larval surveys
      with occasional pupal surveys (to be conducted during the wet season) for
      identifying and subsequently targeting productive container types; 2) the need to
      raise public awareness about useful and effective interventions in productive
      container types specific to their area; and 3) the motivation for control
      services that-according to this and similar studies in Asia- dedicated, targeted
      vector management can make a difference in terms of reducing vector abundance.

PMID- 24447798
TI  - Dirofilaria repens infection in a dog imported to Norway.
AB  - Dirofilaria repens infection was diagnosed in a dog that had been imported to
      Norway from Hungary three years previously. The dog was a four-year-old castrated
      male mixed-breed dog and presented for examination of two masses on the right
      thoracic wall. Fine needle sampling from the subcutaneous nodules and subsequent
      cytological examination revealed a high number of microfilariae and a
      pyogranulomatous inflammation. At re-examination approximately 3 weeks later,
      both masses had apparently disappeared spontaneously, based on both inspection
      and palpation. However, examination of peripheral blood by a modified Knott's
      test revealed a high number of unsheathed microfilariae with mean length of 360
      MUm and mean width of 6-7 MUm, often with the classic umbrella handle appearance
      of D. repens. Polymerase chain reaction and sequencing confirmed the D. repens
      diagnosis. Subcutaneous dirofilariosis caused by D. repens is probably the most
      common cause of human zoonotic dirofilariosis in Europe, but currently is rarely
      encountered in northern countries such as Norway. However, travelling, import and
      relocation of dogs have increased, and thus the geographical range of these
      parasites is likely to increase from traditionally endemic southern regions.
      Increasing numbers of autochthonous cases of D. repens infections in dogs have
      been reported in eastern and central Europe. Although infection with D. repens
      often induces only mild signs or subclinical infections in dogs, they
      nevertheless represent a reservoir for zoonotic transmission and thus a public
      health concern, and, in addition, due to the long prepatent period and the high
      frequency of subclinical infections or infections with unspecific clinical signs,
      could easily be missed. Lack of experience and expectation of these parasites may
      mean that infection is underdiagnosed in veterinary clinics in northern
      countries. Also, predicted climate changes suggest that conditions in some
      countries where this infection is currently not endemic are likely to become more
      suitable for development in the intermediate host, and thus the establishment of
      the infection in new areas.

PMID- 24447799
TI  - Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of
      metformin HCl.
AB  - Jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)
      gellan gum (GG) mucoadhesive beads containing metformin HCl were developed
      through ionotropic gelation technique. The effect of GG to JFSS ratio and CaCl2
      concentration on the drug encapsulation efficiency (DEE, %) and cumulative drug
      release at 10h (R10h, %) was optimized and analyzed using response surface
      methodology based on 3(2) factorial design. The optimized JFSS-GG beads
      containing metformin HCl showed DEE of 92.67+/-4.46%, R10h of 61.30+/-2.37%, and
      mean diameter of 1.67+/-0.27 mm. The optimized beads showed pH-dependent swelling
      and mucoadhesivity with the goat intestinal mucosa. The in vitro drug release
      from all these JFSS-GG beads containing metformin HCl was followed zero-order
      pattern (R(2)=0.9907-0.9975) with super case-II transport mechanism over a period
      of 10 h. The beads were also characterized by SEM and FTIR. The optimized JFSS-GG
      beads containing metformin HCl exhibited significant hypoglycemic effect in
      alloxan-induced diabetic rats over prolonged period after oral administration.

PMID- 24447800
TI  - A series of collision tumors in the genitourinary tract with a review of the
      literature.
AB  - Collision tumors, characterized by the coexistence of phenotypically and
      genotypically distinct tumors at the same site, are distinctly rare in the
      genitourinary tract and pose a diagnostic challenge. The goal of this study is to
      present a series of such cases from a single institution highlighting the unusual
      clinicopathologic features of these tumors. Six cases were retrospectively
      identified from our surgical pathology files and included internal and
      consultation cases (2006-2012). All tumors were identified by H&E and selected
      immunohistochemistry. There were 5 males and 1 female patients ranging in age
      from 57 to 84 years (average 73 years). The sites of these collision tumors were
      located in the kidney (3 cases), bladder (2 cases), and prostate. All collision
      tumors involved at least one malignant neoplasm. The diagnosis of collision
      tumors in the genitourinary tract is a perplexing task. Awareness of these rare
      entities, thorough sampling of the tumor mass, and appropriate use of ancillary
      techniques to demonstrate the different tumor components can help avoid an
      incorrect diagnosis, as well as with pathologic staging. 

PMID- 24447801
TI  - Prostate epithelium-specific deletion of the selenocysteine tRNA gene Trsp leads
      to early onset intraepithelial neoplasia.
AB  - Although various lines of evidence suggest that oxidative stress plays a role in
      human prostate cancer initiation and progression, there is a paucity of direct
      evidence for its role in tumor initiation. To begin to address this issue, we
      developed a novel tumorigenesis model by reducing the expression of multiple
      selenoproteins (SPs) in mouse prostatic epithelium. This was accomplished via the
      prostate-specific deletion of Trsp, a gene that encodes a transfer RNA (Sec tRNA)
      required for the insertion of selenocysteine residues into SPs during their
      translation. By 6 weeks of age, Trsp-deficient mice exhibited widespread
      prostatic intraepithelial neoplasia lesions in all prostatic lobes, which then
      progressed to high-grade dysplasia and microinvasive carcinoma by 24 weeks. In
      contrast to other murine prostate cancer models, Trsp-deficient mice required
      neither the deletion of a tumor suppressor nor the transgenic introduction of an
      oncogene for prostatic intraepithelial neoplasia lesion development. In keeping
      with the antioxidant functions of several SPs, we found increases in lipid
      peroxidation markers in Trsp-deficient epithelial cells. This novel model of
      prostate neoplasia provides evidence for the existence of a selenoprotein or
      selenoproteins capable of acting as a tumor suppressor in the murine prostate. 

PMID- 24447802
TI  - Empirical validation of the "Pediatric Asthma Hospitalization Rate" indicator.
AB  - BACKGROUND: Quality assessment in pediatric care has recently gained momentum.
      Although many of the approaches to indicator development are similar regardless
      of the population of interest, few nationwide sets of indicators specifically
      designed for assessment of primary care of children exist. We performed an
      empirical analysis of the validity of "Pediatric Asthma Hospitalization Rate"
      indicator under the assumption that lower admission rates are associated with
      better performance of primary health care. METHODS: The validity of "Pediatric
      Asthma Hospitalization Rate" indicator proposed by the Agency for Healthcare
      Research and Quality in the Italian context was investigated with a focus on
      selection of diagnostic codes, hospitalization type, and risk adjustment.
      Seasonality and regional variability of hospitalization rates for asthma were
      analyzed for Italian children aged 2-17 years discharged between January 1, 2009,
      and December 31, 2011 using the hospital discharge records database. Specific
      rates were computed for age classes: 2-4, 5-9, 10-14, 15-17 years. RESULTS: In
      the years 2009-2011 the number of pediatric hospitalizations for asthma was
      14,389 (average annual rate: 0.52 per 1,000) with a large variability across
      regions. In children aged 2-4 years, the risk of hospitalization for asthma was
      14 times higher than in adolescents, then it dropped to 4 in 5- to 9-year-olds
      and to 1.1 in 10- to 14-year-olds. The inclusion of diagnoses of bronchitis
      revealed that asthma and bronchitis are equally represented as causes of hospital
      admissions and have a similar seasonality in preschool children, while older age
      groups experience hospital admissions mainly in spring and fall, this pattern
      being consistent with a diagnosis of atopic asthma. Rates of day hospital
      admissions for asthma were up to 5 times higher than the national average in
      Liguria and some Southern regions, and close to zero in some Northern regions.
      CONCLUSIONS: The patterns of hospitalization for pediatric asthma in Italy showed
      that at least two different indicators are needed to measure accurately the
      quality of care provided to children. The candidate indicators should also
      include day hospital admissions to better assess accessibility. Future evaluation
      by a structured clinical panel review at the national level might be helpful to
      refine indicator definitions and risk groupings, to determine appropriate
      application for such measures, and to make recommendations to policy makers.

PMID- 24447803
TI  - Targeted 16S rRNA high-throughput sequencing to characterize microbial
      communities during composting of livestock mortalities.
AB  - AIM: A comprehensive understanding of the microbial community is necessary to
      ensure a significant reduction in pathogens during the composting process.
      METHODS AND RESULTS: Two biosecure, static composting systems containing cattle
      mortalities were constructed at subzero temperatures. Temperature at each
      sampling site was measured continuously and samples were grouped as either <=50
      or >=55 degrees C, based on temperature exposure required for effective pathogen
      inactivation during composting. High-throughput 454 sequencing was used to
      characterize the bacterial communities within each sample. Clustering of
      bacterial communities was observed according to temperature. However, neither
      richness nor diversity differed between temperature groups. Firmicutes was the
      most abundant phylum within both temperature groups but was more pronounced
      (63.6%) in samples >=55 degrees C (P < 0.05). Similarly, members of Clostridia,
      Clostridium sensu stricto (3.64%), Clostridium XI (0.59%), UF (Clostridiaceae 1)
      (5.29%) and UF (Clostridiales Incertae Sedis XI) (6.20%), were prominent at >=55
      degrees C (P < 0.05), likely a reflection of spore survival and/or anaerobic
      microenvironments within passively aerated compost piles. Members of Thermobifida
      (3.54%), UO (Actinomycetales) (12.29%) and UO (Bacillales) (19.49%) were also
      prominent at >=55 degrees C (P < 0.05). CONCLUSION: Substantial spatial diversity
      exists within bacterial communities in field-scale compost piles. Localized
      temperature at the site of sampling may be one of the factors contributing to
      this phenomenon. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to
      describe the microbial community profile with the use of targeted 16S rRNA high
      throughput sequencing in passively aerated composted livestock mortalities.

PMID- 24447804
TI  - Validation of early risk-prediction models for gestational diabetes based on
      clinical characteristics.
AB  - AIMS: Gestational diabetes (GDM) is generally diagnosed late in pregnancy,
      precluding early preventive interventions. This study aims to validate, in a
      large Caucasian population of pregnant women, models based on clinical
      characteristics proposed in the literature to identify, early in pregnancy, those
      at high risk of developing GDM in order to facilitate follow up and prevention.
      METHODS: This is a cohort study including 7929 pregnant women recruited
      prospectively at their first prenatal visit. Clinical information was obtained by
      a self-administered questionnaire and extraction of data from the medical
      records. The performance of four proposed clinical risk-prediction models was
      evaluated for identifying women who developed GDM and those who required insulin
      therapy. RESULTS: The four models yielded areas under the receiver operating
      characteristic curve (AUC) between 0.668 and 0.756 for the identification of
      women who developed GDM, a performance similar to those obtained in the original
      studies. The best performing model, based on ethnicity, body-mass index, family
      history of diabetes and past history of GDM, resulted in sensitivity, specificity
      and AUC of 73% (66-79), 81% (80-82) and 0.824 (0.793-0.855), respectively, for
      the identification of GDM cases requiring insulin therapy. CONCLUSIONS: External
      validation of four risk-prediction models based exclusively on clinical
      characteristics yielded a performance similar to those observed in the original
      studies. In our cohort, the strategy seems particularly promising for the early
      prediction of GDM requiring insulin therapy. Addition of recently proposed
      biochemical markers to such models has the potential to reach a performance
      justifying clinical utilization.

PMID- 24447805
TI  - Pruritus induced self injury behavior: an overlooked risk factor for amputation
      in diabetic neuropathy?
AB  - Pruritus is a risk factor for self-injury behavior (SIB) in sensory
      polyneuropathies. Although diabetes patients have elevated risk for pruritus,
      there are no reports of SIB in diabetic neuropathy. We present the case of a
      diabetes patient with neuropathy, whose pruritus induced SIB, resulted in partial
      amputation of a toe. 

PMID- 24447806
TI  - The effects of urokinase-type plasminogen activator (uPA) on cell proliferation
      and phenotypic transformation of rat mesangial cells induced by high glucose.
AB  - AIMS: To investigate the effects of urokinase-type plasminogen activator (uPA) on
      proliferation and phenotypic transformation of rat mesangial cells (MCs) under
      high glucose conditions and its possible signal transduction pathway. METHODS:
      Rat MC were divided into 4 groups: the control group, the high glucose group, the
      high glucose and wortmannin group, and the high glucose and uPA group. MC
      proliferation in all groups was detected by the 3-(4,5-dimethylthiazol-)-2,5
      diphenyltetrazolium bromide (MTT) method. MC cell cycle was analyzed by flow
      cytometry. Expression of cyclin dependent kinase 2 (CDK2), and activity of the
      signaling protein Akt in MC were detected by Western blot. Expression pattern and
      quantity of alpha-smooth muscle actin (alpha-SMA) in MC were examined using laser
      confocal microscopy. The expression of plasminogen activator inhibitor-1 (PAI-1),
      and collagen IV in renal tissues in rats was tested with immunohistochemistry and
      Western blotting methods. RESULTS: Activation of Akt induced by high glucose can
      be reduced significantly by wortmannin and uPA. There was no obvious change in
      CDK2 protein expression in different groups (P>0.05). Expression of alpha-SMA in
      MC cytoplasm increased dramatically (P<0.01). Expression of alpha-SMA decreased
      significantly in the high glucose and wortmannin group and the high glucose and
      uPA group compared with that of the high glucose group (P<0.01). In diabetic
      rats, uPA down-regulated PAI-1 and collagen IV expression in mesangial matrix
      (P<0.05). CONCLUSION: uPA antagonizes cell proliferation and phenotypic
      transformation of MCs induced by high glucose through inhibiting Akt signaling
      pathway.

PMID- 24447807
TI  - Severe acute renal failure in patients treated with glucagon-like peptide-1
      receptor agonists.
AB  - We report two patients with diabetes in whom acute renal failure requiring
      hemodialysis occurred while on treatment with glucagon-like peptide-1 receptor
      agonists. We discuss the mechanisms of this complication and the potential for
      its prevention. 

PMID- 24447808
TI  - Trends in the prevalence of diabetes and impaired fasting glucose in association
      with obesity in Iran: 2005-2011.
AB  - AIMS: To estimate the prevalence and trends of diabetes mellitus (DM) and
      impaired fasting glucose (IFG), 2005-2011, and to determine the contribution of
      obesity to DM prevalence. PATIENTS AND METHODS: Data from Surveillance of Risk
      Factors of Non-communicable Diseases (SuRFNCD) conducted in 2005, 2007, and 2011
      were gathered. DM was defined as presence of self-reported previous diagnosis or
      a fasting plasma glucose (FPG)>=7 mmol/L. IFG was diagnosed with FPG levels
      between 5.6 and 6.9 mmol/L. Prevalence rates for 2011 and trends for 2005-2011
      were determined by extrapolating survey results to Iran's adult population.
      Population attributable fraction (PAF) of obesity was also calculated. RESULTS:
      In 2011, IFG and total DM prevalence rates were 14.60% (95%CI: 12.41-16.78) and
      11.37% (95%CI: 9.86-12.89) among 25-70 years, respectively. DM was more common in
      older age (p < 0.0001), in women (p = 0.0216), and in urban-dwellers (p =
      0.0001). In 2005-2011, trend analysis revealed a 35.1% increase in DM prevalence
      (OR: 1.04, 95%CI: 1.01-1.07, p = 0.011); albeit, IFG prevalence remained
      relatively unchanged (OR: 0.98, 95%CI: 0.95-1.00, p = 0.167). In this period, DM
      awareness improved; undiagnosed DM prevalence decreased from 45.7% to 24.7% (p <
      0.001). PAF analysis demonstrated that 33.78%, 10.25%, and 30.56% of the
      prevalent DM can be attributed to overweight (BMI>=25kg/m(2)), general obesity
      (BMI>=30 kg/m(2)), and central obesity (waist circumference>=90 cm),
      respectively. Additionally, the DM increase rate in 2005-2011, was 20 times
      higher in morbidly obese compared with lean individuals. CONCLUSION: More than
      four million Iranian adults have DM which has increased by 35% over the past
      seven years, owing in large part, to expanding obesity epidemic.

PMID- 24447809
TI  - Maternal serum and fetal cord blood irisin levels in gestational diabetes
      mellitus.
AB  - AIM: To investigate the relationship between maternal and cord blood irisin in
      gestational diabetes mellitus (GDM). METHODS: Twenty women with GDM and 20
      pregnant women with uncomplicated pregnancies were recruited for this case
      control study. Maternal serum irisin and cord blood irisin levels were measured
      by enzyme-linked immunosorbent assay kit at the time of birth. The association of
      maternal serum and cord blood irisin levels with metabolic parameters was
      analyzed. RESULTS: Women with GDM had significantly lower mean serum irisin
      levels compared to control group (258.3+/-127.9 vs. 393+/-178.9ng/ml, p<0.05).
      Mean cord blood irisin levels for GDM and control groups were not significantly
      different (357.2+/-248.0 vs. 333.2+/-173.4ng/ml, p>0.05). No significant
      differences were found in terms of maternal age, gestational week at birth, BMI
      at birth, birth weight, neonatal height, systolic and diastolic blood pressure
      between the groups as well (p>0.05). Serum irisin level was negatively correlated
      with BMI at birth and HOMA-IR (r=-0.401, p=0.010; r=-0.395, p=0.012,
      respectively). No correlations between irisin levels and others parameters were
      found in both groups. CONCLUSIONS: Maternal serum irisin levels of patients with
      GDM are significantly lower compared with non-GDM controls. However, no
      significant difference was found between cord blood irisin levels of patients
      with GDM and healthy pregnant women.

PMID- 24447811
TI  - Carbohydrate counting with an automated bolus calculator helps to improve
      glycaemic control in children with type 1 diabetes using multiple daily injection
      therapy: an 18-month observational study.
AB  - AIMS: This study aimed to investigate the effect of carbohydrate counting
      (carbC), with or without an automated bolus calculator (ABC), in children with
      type 1 diabetes treated with multiple daily insulin injections. METHODS: We
      evaluated 85 children, aged 9-16 years, with type 1 diabetes, divided into four
      groups: controls (n=23), experienced carbC (n=19), experienced carbC+ABC (n=18)
      and non-experienced carbC+ABC (n=25). Glycated haemoglobin (HbA1c), insulin use,
      and glycaemic variability - evaluated as high blood glucose index (HBGI) and low
      blood glucose index (LBGI) - were assessed at baseline and after 6 and 18 months.
      RESULTS: At baseline, age, disease duration, BMI, HbA1c, insulin use, and HBGI
      (but not LBGI; p=0.020) were similar for all groups. After 6 months, HbA1c
      improved from baseline, although not significantly - patients using ABC
      (according to manufacturer's recommendations) HbA1c 7.14 +/- 0.41% at 6 months
      vs. 7.35 +/- 0.53% at baseline, (p=0.136) or without carbC experience HbA1c
      7.61+/-0.62% vs. 7.95 +/- 0.99% (p=0.063). Patients using ABC had a better HBGI
      (p=0.001) and a slightly worse LBGI (p=0.010) than those not using ABC. ABC
      settings were then personalised. At 18 months, further improvements in HbA1c were
      seen in children using the ABC, especially in the non-experienced carbC group (
      0.42% from baseline; p=0.018). CONCLUSIONS: CarbC helped to improve glycaemic
      control in children with type 1 diabetes using multiple daily injections. ABC use
      led to greater improvements in HbA1c, HBGI and LBGI compared with patients using
      only carbC, regardless of experience with carbC.

PMID- 24447810
TI  - Comparison of type 2 diabetes prevalence estimates in Saudi Arabia from a
      validated Markov model against the International Diabetes Federation and other
      modelling studies.
AB  - AIMS: To compare the estimates and projections of type 2 diabetes mellitus (T2DM)
      prevalence in Saudi Arabia from a validated Markov model against other modelling
      estimates, such as those produced by the International Diabetes Federation (IDF)
      Diabetes Atlas and the Global Burden of Disease (GBD) project. METHODS: A
      discrete-state Markov model was developed and validated that integrates data on
      population, obesity and smoking prevalence trends in adult Saudis aged >=25 years
      to estimate the trends in T2DM prevalence (annually from 1992 to 2022). The model
      was validated by comparing the age- and sex-specific prevalence estimates against
      a national survey conducted in 2005. RESULTS: Prevalence estimates from this new
      Markov model were consistent with the 2005 national survey and very similar to
      the GBD study estimates. Prevalence in men and women in 2000 was estimated by the
      GBD model respectively at 17.5% and 17.7%, compared to 17.7% and 16.4% in this
      study. The IDF estimates of the total diabetes prevalence were considerably lower
      at 16.7% in 2011 and 20.8% in 2030, compared with 29.2% in 2011 and 44.1% in 2022
      in this study. CONCLUSION: In contrast to other modelling studies, both the Saudi
      IMPACT Diabetes Forecast Model and the GBD model directly incorporated the trends
      in obesity prevalence and/or body mass index (BMI) to inform T2DM prevalence
      estimates. It appears that such a direct incorporation of obesity trends in
      modelling studies results in higher estimates of the future prevalence of T2DM,
      at least in countries where obesity has been rapidly increasing.

PMID- 24447812
TI  - Endothelin-1 mediated high glucose-induced epithelial-mesenchymal transition in
      renal tubular cells.
AB  - OBJECTIVE: The pathogenesis of interstitial fibrosis in diabetic nephropathy (DN)
      is an intractable problem without good therapy. Emerging evidence suggests that
      epithelial-mesenchymal transition (EMT) is an important mechanism for tubular
      epithelial cells undergoing profibrotic change in DN. Endothelin-1 (ET-1) is an
      important cytokine which can cause fibrogenesis and is reportedly involved in DN.
      However, the role of ET-1 in EMT in DN is unknown. The present study was designed
      to investigate the role of ET-1 in high glucose-induced EMT and the signaling
      pathway mediating the effect of ET-1 in renal tubular cells. METHOD: Tubular
      epithelial cells (NRK52E) were treated with normal glucose (d-glucose 5.6mmol/L,
      NG), high glucose (30mmol/L, HG), high osmotic (d-glucose 5.6mmol/L+d-mannitol
      24.4mmol/L), HG+ETA antagonist BQ123 (2MUg/ml), ET-1, ET-1+ hypoxia inducible
      factor (HIF)-1alpha siRNA, CoCl2 (100MUmol/L), CoCl2+HIF-1alpha siRNA or
      CoCl2+BQ123. The supernatant level of ET-1 was measured by ELISA and the
      expression of vimentin, E-cadherin and HIF-1alpha was detected by RT-PCR and
      western blot. RESULT: The ET-1 level increased markedly in the supernatant of
      NRK52E incubated with HG. In NRK52E induced with HG or ET-1, the expression of
      vimentin was upregulated, whereas the expression of E-cadherin was downregulated.
      BQ123 attenuated HG- and CoCl2-induced EMT while HIF-1alpha siRNA did not affect
      ET-1 induced EMT. CONCLUSIONS: High glucose induced ET-1 production that mediated
      the EMT induced by high glucose in renal tubular epithelial cells, and HIF-1alpha
      acted as the upstream signal to regulate ET-1.

PMID- 24447813
TI  - Video Q&A: allergies and allergen immunotherapy--an interview with Alfred William
      Frankland.
AB  - In this video Q&A, we talk to Dr Alfred William Frankland about the highlights of
      his career, including working alongside Sir Alexander Fleming, co-founding the
      British Allergy Society, and introducing pollen counts to UK weather forecasts.
      We also discuss his opinions on why misconceptions about allergies and allergen
      immunotherapy still exist. Please see related article:
      http://www.biomedcentral.com/1741-7015/11/255.

PMID- 24447814
TI  - Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L.
      fruits.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the recent years, the international community
      has attached increasing importance to possible toxicity associated with
      Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major
      concerns, a fundamental pathological process induced by toxicant. This paper is
      in an attempt to identify the hepatotoxic components in Xanthium strumarium L.
      fruits (XSF) and interpret the toxicological mechanism induced by XSF. MATERIALS
      AND METHODS: XSF extract was prepared and seven characteristic components were
      isolated and identified in XSF water extracts. We evaluated their hepatotoxicity
      effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and
      BRL liver cell line. An integrated metabonomics study using high-resolution (1)H
      nuclear magnetic resonance ((1)H NMR) spectroscopy combined with multivariate
      statistical analysis was undertake to elucidate the hepatotoxicity mechanism
      induced in rats by XSF. The urine and serum metabolites were measured after
      treatment of rats with XSF (7.5, 15.0 and 30.0 g/kg/day) for 5 days. RESULTS: The
      results showed that atractyloside, carboxyatractyloside, 4'-desulphate
      atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL
      liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'
      desulphate-atractyloside were the toxic components of XSF. When rats were treated
      with XSF at 30.0 g/kg the hepatotoxicity was reflected in the changes observed in
      serum biochemical profiles and by the histopathological examination of the liver.
      The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum
      were increased in this group, while d-glucose, choline and valine were decreased.
      The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3
      HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine,
      phenylalanine and tryptophan was observed in urine, in contrast a reduction in
      the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine-N
      oxide (TMAO) was observed. CONCLUSIONS: The results demonstrate that the major
      hepatotoxicity constituents are atractyloside, carboxyatractyloside and 4'
      desulphate-atractyloside, and the hepatotoxicity of XSF involves mitochondrial
      inability, fatty acid metabolism, and some amino acids metabolism. This
      integrated (1)H NMR -based metabolic profiling approach has been able to capture
      and probe the metabolic alterations associated with the onset and progression of
      hepatotoxicity induced by XSF, and permits a comprehensive understanding of
      systemic toxicity for phytochemicals and other types of xenobiotic agents.

PMID- 24447816
TI  - Ocular dimensions in relation to auxological data in a sample of Swedish children
      aged 4-15 years.
AB  - PURPOSE: The purpose was to characterize normal growth patterns of ocular and
      optical components and to relate them to auxological data in a sample of Swedish
      children aged 4-15 years. METHODS: A prospective cross-sectional study was
      carried out in 143 Swedish children with a mean age of 9.8 years. Variables
      including gestational age (GA), weight, length and head circumference (HCF) at
      birth and at the time of assessment were registered. Visual acuity (VA),
      cycloplegic refraction and biometric measures were obtained. Palpebral fissure
      length and inner canthal distance were measured. Optic disc morphology as seen on
      fundus photographs was analysed. RESULTS: Children born more mature, with male
      predilection, were found to have deeper anterior and vitreous chamber depths,
      longer axial lengths and thinner crystalline lens thickness. No correlations were
      found between ocular biometric measurements and VA or refraction after adjustment
      for confounding variables. Inner canthal distance was significantly correlated
      with birth length (p = 0.03), height, weight, BMI and HCF (p = 0.0008, p =
      0.0007, p = 0.037, and p = 0.04, respectively) at time of assessment. Total axial
      length was found to be significantly correlated with GA (p = 0.0226) and length
      at assessment in girls (p = 0.0084). Right optic disc and rim areas decreased
      with increasing age (p = 0.0078 and p = 0.0107, respectively); however, optic
      disc parameters were not dependent on any other variable. CONCLUSION: These
      normative values may serve as a basis for the ocular findings and their
      relationship to auxological data in Caucasian children aged 4-15 years, as well
      as for future comparison in patients with paediatric ocular pathologies.

PMID- 24447815
TI  - [Anaesthetic-surgical management of a patient diagnosed with cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy].

PMID- 24447817
TI  - Characterization of a monoclonal antibody capable of reliably quantifying
      expression of human Copper Transporter 1 (hCTR1).
AB  - Human copper transporter 1 (hCTR1) is the high-affinity copper influx transporter
      in mammalian cells that also mediates the influx of cisplatin. Loss of hCTR1
      expression has been implicated in the development of resistance to this cancer
      chemotherapeutic agent. It has turned out to be very difficult to develop
      antibodies to hCTR1 and polyclonal antibodies produced by different laboratories
      have yielded conflicting results. We have characterized a newly-available rabbit
      monoclonal antibody that reacts with an epitope on the N-terminal end of hCTR1
      that now permits rigorous identification and quantification of hCTR1 using
      Western blot analysis. Postnuclear membrane (PNM) preparations made from cells
      engineered to express high levels of myc-tagged hCTR1, and cells in which the
      expression of hCTR1 was knocked down, were used to characterize the antibody. The
      identity of the bands detected was confirmed by immunoprecipitation, surface
      biotinylation and deglycosylation of myc-tagged hCTR1. Despite the specificity
      expected of a monoclonal antibody, the anti-hCTR1 detected a variety of bands in
      whole cell lysates (WCL), which made it difficult to quantify hCTR1. This problem
      was overcome by isolating post-nuclear membranes and using these for further
      analysis. Three bands were identified using this antibody in PNM preparations
      that migrated at 28, 33-35 and 62-64kDa. Multiple lines of evidence presented
      here suggest that the 33-35 and 62-64kDa bands are hCTR1 whereas the 28kDa band
      is a cross-reacting protein of unknown identify. The 33-35kDa band is consistent
      with the expected MW of the glycosylated hCTR1 monomer. This analysis now permits
      rigorous identification and quantification of hCTR1. 

PMID- 24447818
TI  - Co-circulation of West Nile virus variants, Arizona, USA, 2010.
AB  - Molecular analysis of West Nile virus (WNV) isolates obtained during a 2010
      outbreak in Maricopa County, Arizona, USA, demonstrated co-circulation of 3
      distinct genetic variants, including strains with novel envelope protein
      mutations. These results highlight the continuing evolution of WNV in North
      America and the current complexity of WNV dispersal and transmission. 

PMID- 24447819
TI  - Impact of genomic diversity in river ecosystems.
AB  - We propose that genomic diversity in aquatic macrophytes of rivers, driven by the
      underlying genomic processes of interspecific hybridization and polyploidy (whole
      genome duplication), play a significant role in ecosystem functioning. These
      genomic processes generate individuals which might differ in their demands for
      nitrogen (N) and phosphorus (P). This is significant because (i) N and/or P are
      frequently limiting nutrients in freshwater ecosystems, and (ii) nucleic acids
      are demanding in N and P. We suggest that N and P availability will provide a
      selection pressure for genetic variants in macrophytes which will, in turn,
      influence the nutritional quality of plant biomass, and hence their consumption
      by herbivores and detritivores as well as the energy flux of their biomass
      through the food web. 

PMID- 24447820
TI  - Polymorphism of P53-Ets/AP1 transactivation region of MDM2 oncogene and its
      immunohistochemical analysis in canine tumours.
AB  - Mouse Double Minute-2 (MDM2) is an ubiquitin ligase which is overexpressed or its
      promoter polymorphism has been reported in different tumours. The objective of
      this study was to examine the MDM2 protein expression and its promoter
      polymorphism in some canine tumours. Twenty specimens were collected from 20 dogs
      with 15 mammary gland carcinomas, 3 lymphomas, 1 transmissible venereal tumour
      and 1 trichoblastoma. Samples were analysed immunohistochemically using human
      antibody against MDM2 protein. PCR and DNA sequencing were carried out to
      identify MDM2 promoter polymorphism. MDM2 gene was expressed in 13 of 20 samples
      including 11 mammary carcinomas, 1 lymphoma and 1 trichoblastoma. We found 94%
      homology between canine and human sequences. Four mutations including G169C,
      A177G, G291T and A177G were identified in different types of breast carcinomas.
      An extra p53 response element was found in a mixed mammary carcinoma. 

PMID- 24447821
TI  - Assessing the cells in the lung lavage: an untapped resource in lung transplant
      monitoring.

PMID- 24447822
TI  - "It's my blood": ethical complexities in the use, storage and export of
      biological samples: perspectives from South African research participants.
AB  - BACKGROUND: The use of biological samples in research raises a number of ethical
      issues in relation to consent, storage, export, benefit sharing and re-use of
      samples. Participant perspectives have been explored in North America and Europe,
      with only a few studies reported in Africa. The amount of research being
      conducted in Africa is growing exponentially with volumes of biological samples
      being exported from the African continent. In order to investigate the
      perspectives of African research participants, we conducted a study at research
      sites in the Western Cape and Gauteng, South Africa. METHODS: Data were collected
      using a semi-structured questionnaire that captured both quantitative and
      qualitative information at 6 research sites in South Africa. Interviews were
      conducted in English and Afrikaans. Data were analysed both quantitatively and
      qualitatively. RESULTS: Our study indicates that while the majority of
      participants were supportive of providing samples for research, serious concerns
      were voiced about future use, benefit sharing and export of samples. While
      researchers view the provision of biosamples as a donation, participants believe
      that they still have ownership rights and are therefore in favour of benefit
      sharing. Almost half of the participants expressed a desire to be re-contacted
      for consent for future use of their samples. Interesting opinions were expressed
      with respect to export of samples. CONCLUSIONS: Eliciting participant
      perspectives is an important part of community engagement in research involving
      biological sample collection, export, storage and future use. A tiered consent
      process appears to be more acceptable to participants in this study. Eliciting
      opinions of researchers and research ethics committee (REC) members would
      contribute multiple perspectives. Further research is required to interrogate the
      concept of ownership and the consent process in research involving biological
      samples.

PMID- 24447823
TI  - External validation of the CURSI criteria (confusion, urea, respiratory rate and
      shock index) in adults hospitalised for community-acquired pneumonia.
AB  - BACKGROUND: For patients hospitalised due to community-acquired pneumonia (CAP),
      mortality risk is usually estimated with prognostic scores such as CRB-65 or CURB
      65. For elderly patients, a new score referred to as CURSI has been proposed
      which uses shock index (SI) instead of the blood pressure (B) and age (65)
      criteria. The new score has not been externally validated to date. METHODS: We
      used data from a hospital-based CAP registry to compare the ability of CURSI,
      CURB-65 and CRB-65 to predict mortality at day 30 after hospital admission.
      Patients were stratified by score points as well as score-point-based risk
      categories, and mortality for each group was assessed. To compare test
      performance, receiver-operating characteristic (ROC) curves were constructed, and
      the areas under the curve (AUROC) were calculated with 95% confidence intervals
      (CI). RESULTS: We analysed 553 inpatients (45% females, median age 78 years)
      hospitalised between 2005 and 2009 for CAP. Overall, mortality at day 30 was 11%
      (59/553). The study sample was characterised by advanced comorbidity (chronic
      heart failure: 22%, chronic kidney failure: 27%) and functional impairment
      (nursing home residency: 26%, dementia: 31%). All risk scores were significantly
      associated with 30-day mortality. The AUROC values with 95% CI using score points
      for risk prediction were as follows: 0.63 [0.56-0.71] for CRB-65, 0.68 [0.61
      0.75] for CURB-65 and 0.68 [0.61-0.75] for CURSI. The CURSI-defined low-risk
      group (0 or 1 score point) had a higher mortality (8%) than the low-risk groups
      defined by CURB-65 and CRB-65 (4% and 3%, respectively). Lowering the cut-off for
      the CURSI-defined low-risk group (0 point only) would lower the mortality to 4%,
      making it comparable to the CURB-65-defined low-risk group. CONCLUSIONS: In our
      study, the CURSI-defined low-risk group had a higher 30-day mortality than the
      low-risk groups defined by CURB-65 and CRB-65. Lowering the cut-off value for the
      CURSI low-risk group would result in a mortality comparable to the CURB-65
      defined low risk group. Even then, however, CURSI does not perform better than
      the established risk scores.

PMID- 24447824
TI  - Infectious Schmallenberg virus from bovine semen, Germany.

PMID- 24447825
TI  - Stage, grade and pathological characteristics of bladder cancer in the UK:
      British Association of Urological Surgeons (BAUS) urological tumour registry.
AB  - OBJECTIVE: To investigate Tumour-Node-Metastasis (TNM) stage and demographics at
      presentation in a very large, contemporary UK cohort of patients with bladder
      cancer and compare them with other published series, as little published data
      exists on the pathological characteristics of bladder cancer at presentation.
      PATIENTS AND METHODS: The British Association of Urological Surgeons (BAUS)
      Section of Oncology started a new urological tumour registry in 1998. We
      performed a data analysis of all bladder cancer cases between 1999 and 2008.
      Tumour TNM stage, grade and histopathological diagnosis were reviewed along with
      standard epidemiological data. RESULTS: In all, 69,712 bladder cancer
      registrations were recorded. Complete T, N and M stage and grade was available
      for 32,240 patients. The male to female ratio of the study population was 3:1 and
      the overall median (sd, range) age at presentation was 73 (11.6, 6-108) years.
      Final pathological T staging showed that non-muscle-invasive bladder cancer
      accounted for 75% of cases with the remaining 25% being muscle-invasive disease.
      Of these patients, 8% had nodal disease and 4% other metastatic sites at
      presentation. The tumour grade was G1-2 in 65% and G3 in 35% of cases.
      Transitional cell carcinoma (TCC) accounted for 92%, squamous cell carcinoma and
      adenocarcinomas 1.5% each, with 5% other histological variants. CONCLUSIONS: Non
      muscle-invasive TCC accounted for 75% of bladder cancer cases in the UK. The 1973
      World Health Organization classification remains in widespread use amongst
      pathologists in the UK. Obtaining complete and standardised staging and pathology
      reporting systems in bladder cancer remains a challenge.

PMID- 24447826
TI  - The hypoglycemic effect of Juglans regia leaves aqueous extract in diabetic
      patients: A first human trial.
AB  - BACKGROUND: Juglans regia L. (J. regia ) is one of the medicinal plants
      traditionally used for treatment of diabetes in Iranian medicine. The effect of
      this plant has already been investigated on animal models; however, this is the
      first study conducted on human subjects. The aim of this study is to investigate
      the hypoglycemic effect of J. regia leaves aqueous extract in type 2 diabetes
      patients. Fifty eight Iranian male and female patients with type 2 diabetes were
      enrolled. The patients were randomly allocated into two groups. One group (n =
      30) received J. regia leaves extract while the other group (n = 28) received
      placebo. Fasting blood samples were collected at the beginning of the study and
      after two months for determination of HbA1c and blood glucose level as a main
      outcome and insulin, SGOT, SGPT, and ALP level as secondary outcome. RESULTS: Our
      analysis showed that serum fasting HbA1C and blood glucose levels were
      significantly decreased and the insulin level was increased in patients in the J.
      regia arm. CONCLUSIONS: The results indicate that J. regia aqueous extract
      favorably affects blood levels of glucose, insulin and HbA1C in type 2 diabetic
      patients.

PMID- 24447827
TI  - Effects of occupational exposure to chlorpyrifos on neuropsychological function:
      a prospective longitudinal study.
AB  - BACKGROUND: Exposure to chlorpyrifos (CPF), an organophosphorus (OP)
      anticholinesterase insecticide, occurs typically in settings where multiple
      agents are present (e.g., agriculture) and quantitative dose measures may be
      absent (e.g., pesticide application). Such exposures allow few opportunities to
      study potential neurobehavioral effects of CPF alone. We studied the relationship
      between CPF exposure and behavioral function among CPF manufacturing workers,
      which allowed identification, measurement, and estimation of exposure and
      important non-exposure variables that potentially could affect study findings.
      METHODS: A prospective longitudinal study design was used to compare
      neurobehavioral function over a one-year period among 53 CPF workers and 60
      referent workers. Quantitative and qualitative measures were used, and potential
      confounders were identified and tested for possible inclusion in our statistical
      models. Neurobehavioral function was assessed by neuropsychological tests
      covering various behavioral domains that may be adversely affected by exposure to
      CPF in sufficient amount. RESULTS: CPF workers had significantly greater CPF
      exposures during the study period than did referents at levels where physiologic
      effects on plasma butyrylcholinesterase (BuChE) activity were apparent and with
      higher 3,5,6-trichloro-2-pyridinol (TCPy/Cr) urinary excretion (p<0.0001) and
      lower average BuChE activity (p<0.01). No evidence for impaired neurobehavioral
      domains by either group of workers was observed at baseline, on repeat
      examination, or between examinations. CPF workers scored higher than referent
      workers on the verbal memory domain score (p=0.03) at baseline, but there were no
      significant changes in verbal memory over time and no significant group-by-time
      interactions. CONCLUSIONS: The study provides important information about CPF
      exposure in the workplace by not supporting our working hypothesis that CPF
      exposure associated with various aspects of the manufacturing process would be
      accompanied by adverse neurobehavioral effects detectable by quantitative
      neurobehavioral testing. Some aspects making this workplace site attractive for
      study and also present limitations for the generalization of results to other
      situations that might have exposures that vary widely between and within
      different facilities and locations. For example, these results might not apply to
      occupations such as applicators with higher exposure or to workers with low
      educational levels.

PMID- 24447828
TI  - Aging impairs the recovery in mechanical muscle function following 4 days of
      disuse.
AB  - As aged individuals are frequently exposed to short-term disuse caused by disease
      or musculoskeletal injury, it is important to understand how short-term disuse
      and subsequent retraining affect lower limb mechanical muscle function. The
      purpose of the present study was, therefore, to investigate the effect of 4 days
      of lower limb disuse followed by 7 days of active recovery on mechanical muscle
      function of the knee extensors in young (24.3+/-0.9 years, n=11) and old (67.2+/
      1.0 years, n=11) recreationally active healthy males. Slow and moderate dynamic
      muscle strength were assessed using isokinetic dynamometry (60 and 180 degrees 
      s(-1), respectively) along with isometric muscle strength and rapid muscle force
      capacity examined as contractile rate of force development (RFD), Impulse, and
      relative RFD (rRFD) during the initial phase of contraction (100 ms time interval
      relative to onset of contraction). Prior to disuse, marked age-related
      differences (p<0.05) were observed in isometric and dynamic muscle strength
      (~35%) as well as in RFD and Impulse (~39%). Following disuse, young and old
      individuals experienced comparable decrements (p<0.05) in isometric strength
      (~9%), slow dynamic strength (~13%), and RFD and Impulse (~19%), whereas old
      individuals only experienced decrements (p<0.05) in moderate dynamic strength
      (12%) and rRFD (~17%). Following recovery, all measures of mechanical muscle
      function were restored in young individuals compared to pre-disuse values, while
      isometric, slow and moderate dynamic muscle strength remained suppressed (p<0.05)
      in old individuals (~8%) along with a tendency to suppressed RFD100 (p=0.068). In
      conclusion, 4 days of lower limb disuse led to marked decrements in knee extensor
      mechanical muscle function in both young and old individuals, yet with greater
      decrements observed in moderate dynamic strength and rapid muscle force capacity
      in old individuals. While 7 days of recovery - including free ambulation, one
      test session and a single session of strength training - was sufficient to
      restore mechanical muscle function in young individuals, old individuals appeared
      to have an impaired ability to fully recover as evidenced by suppressed values of
      isometric and dynamic muscle strength and rapid muscle force capacity.

PMID- 24447829
TI  - Elastophagocytosis: underlying mechanisms and associated cutaneous entities.
AB  - Elastophagocytosis is the phagocytosis of elastic fibers that can microscopically
      be seen in the cytoplasm of histiocytes, multinucleated giant cells, or both.
      Generally believed to be a characteristic feature of certain granulomatous
      disorders such as annular elastolytic giant cell granuloma or elastolytic
      disorders such as mid-dermal elastolysis, this feature has also been described in
      other cutaneous inflammatory conditions, cutaneous malignancies, infectious
      entities, and secondary to certain medications. The list of diseases that can
      exhibit this peculiar finding on histopathology is long. In this review we
      attempt to shed light on the available literature concerning the pathogenesis of
      this phenomenon and the plethora of skin conditions that exhibit
      elastophagocytosis. 

PMID- 24447831
TI  - An analysis of the ruminal bacterial microbiota in West African Dwarf sheep fed
      grass- and tree-based diets.
AB  - AIMS: To measure the impact of supplementing a forage diet with tree-based browse
      on the ruminal bacterial communities of Nigerian West African Dwarf (WAD) sheep.
      METHODS AND RESULTS: Fifteen WAD sheep were fed a control diet of forage (Panicum
      maximum), with 12 animals shifted in groups of three to one of four browse
      supplemented diets (Albizia saman, Bridelia micrantha, Ficus sur, or Gmelina
      arborea). These browse plants were shown in a concurrent but separate study to be
      reasonably nutritious (based on chemical composition and fibre constituents) and
      nontoxic (based on tannin, phytate, saponin, alkaloid and oxalate levels). Rumen
      liquids and solids for DNA extraction were collected via intubation from two
      animals in each group before and after dietary shift. Bacterial 16S rRNA gene
      regions V6-V8 were sequenced by 454 pyrosequencing. All communities were highly
      diverse and dominated by the phyla Firmicutes, Bacteroidetes, Tenericutes,
      Actinobacteria and Proteobacteria. All communities shared members of the genera
      Butryivibrio, Prevotella and Ruminococcus. Our analysis defined a core sets of
      bacteria shared by all animals, forage-fed animals and browse-fed animals.
      Community structure shifted dramatically in animals fed A. saman or G. arborea.
      CONCLUSIONS: The impact of tree-based browse on the ruminal bacterial community
      of Nigerian WAD sheep varies by browse species, likely due to differences in
      browse composition. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study describes the
      first neotropical small ruminant bacterial microbiome and supports diet
      supplementation with specific tree-based browse for WAD sheep.

PMID- 24447830
TI  - MIF: mood improving/inhibiting factor?
AB  - Although major depressive disorder imposes a serious public health burden and
      affects nearly one in six individuals in developed countries over their
      lifetimes, there is still no consensus on its pathophysiology. Inflammation and
      cytokines have emerged as a promising new avenue in depression research, and, in
      particular, macrophage migration inhibitory factor (MIF) has been shown to be
      significant in depression physiology. In this review we summarize current
      research on MIF and depression. We highlight the arguments for MIF as a pro- and
      antidepressant species and discuss the potential implications for therapeutics. 

PMID- 24447832
TI  - Murine double minute 2 siRNA and wild-type p53 gene therapy interact positively
      with zinc on prostate tumours in vitro and in vivo.
AB  - Prostate cancer (PCa) often shows either mutations of the p53 gene or
      inactivation of the P53 protein. The latter may be due to up-regulation of mouse
      double minute 2 homologue (MDM2), which functions both as an E3 ubiquitin ligase
      to degrade P53 protein via the proteasome and an inhibitor of P53 transcriptional
      activation. Zinc plays a crucial role in stabilizing the P53 DNA binding domain,
      but PCa cells often lack the ability to accumulate sufficient zinc. In the
      present study, we explore the optimal approach to retention of P53 function. To
      restore the defective P53 pathway in PCa, we have explored a combined treatment
      of Pmp53 [a plasmid containing both mdm2 small interfering RNA (Si-MDM2) and the
      wild-type p53 gene] with zinc. This treatment retains the wild-type P53
      conformation and function in PCa in vitro and in vivo. Combined treatments
      significantly inhibited tumour xenograft growth, retaining wild-type P53
      conformation and enhancing its transcriptional regulation of p21 and bax gene
      expression, leading to the decreased proliferation and increased apoptosis. These
      in vivo findings were confirmed by in vitro culture of PCa PC-3 (p53 null) or
      DU145 (mutant p53) cells and showed a positive effect of the combined therapy on
      cell cycle arrest and massive apoptosis. Our findings suggest that the combined
      therapy of Pmp53 with zinc is an effective strategy that may open a new
      therapeutic avenue in some cancers expressing low levels of zinc and a defective
      P53 status. 

PMID- 24447833
TI  - Elderly patients with colorectal cancer: treatment modalities and survival in
      France. National data from the ThInDiT cohort study.
AB  - BACKGROUND: Few data exist on how elderly patients with colorectal cancer (CRC)
      are actually treated in real-life practice. Based on a national cohort, we
      analysed routine treatment modalities of the elderly who were diagnosed with CRC
      in France in 2009. PATIENTS AND METHODS: The characteristics of patients and
      tumours and the cancer treatments received during the first year of all national
      incident cases of CRC diagnosed between 1st April and 31st December 2009, were
      compared between a 'younger group' (YG), under 75 years of age (N = 18,410
      patients), and an 'older group' (OG), aged 75 and over (N = 13,255 patients). In
      the OG with metastases at baseline, we analysed two-year overall survival (OS)
      according to the treatment received (e.g. chemotherapy, surgery) and well-known
      prognostic factors. RESULTS: Among patients with localised CRC (N = 25,353),
      surgery was equally performed in both groups in more than 80% of the cases
      (p=0.52); time to surgery was shorter in the OG (8 versus 23 days) because there
      was more emergency surgery for occlusion among the OG. Adjuvant chemotherapy was
      performed in 15% of the OG (versus 29% in the YG) and consisted of 5-fluorouracil
      (5FU) monotherapy in more than 50% of OG patients. Among patients with metastatic
      CRC (N = 6,312), palliative chemotherapy was given to 48% of the OG versus 85% of
      the YG. Chemotherapy regimens included 30% monotherapy with 5FU, 30% oxaliplatin
      combination and 20% bevacizumab combination in the OG; compared to 10%, 34% and
      35%, respectively, in the YG. The median OS for the OG was 8.4 months (versus
      22.3 months in the YG) and 17.1 months among elderly patients who received
      chemotherapy. CONCLUSION: CRC is more frequently complicated at diagnosis among
      elderly patients. Adjuvant and palliative chemotherapy is less frequently
      prescribed among elderly patients. This could be explained by the fact that unfit
      elderly patients do not deserve chemotherapy, but certainly also reflect the fact
      that some fit elderly patients are undertreated.

PMID- 24447834
TI  - Activation of histamine H4 receptors decreases epithelial-to-mesenchymal
      transition progress by inhibiting transforming growth factor-beta1 signalling
      pathway in non-small cell lung cancer.
AB  - Previous investigations found that epithelial-to-mesenchymal transition (EMT) was
      an important character of non-small cell lung cancer (NSCLC) and it was also
      suggested that histamine H4 receptors may have a role in preventing EMT progress
      in certain kind of tumours. However, the effect of H4 receptor activation on EMT
      progress of NSCLC and its potential mechanisms remain unclear. Therefore, we
      performed both in vitro and in vivo experiments to explore the effects of
      specific H4 receptor agonist 4-methylhistamine and antagonist JNJ7777120 on EMT
      progress. We showed the expression of H4 receptors in NSCLC and found that 4
      methylhistamine increased the expression of the epithelial marker E-cadherin and
      decreased the expression of Vimentin, the mesenchymal marker, in both NSCLC cell
      lines and xenograft NSCLC tumours. Pretreatment with JNJ7777120 or H4 receptor
      gene silencing decreased while overexpression of H4 receptors facilitated this
      effect of 4-methylhistamine. Furthermore, we showed that down-regulation of
      cyclic adenosine monophosphate (cAMP) was the secondary signalling after H4
      receptor activation, which in turn resulted in inactivation of transforming
      growth factor-beta1 (TGF-beta1) pathway and down-regulation of several important
      EMT inducing factors such as ZEB1, Snail and Slug. In conclusion, these findings
      revealed the anti-EMT effect of histamine H4 receptor activation in NSCLC, which
      provide novel insight into the development mechanism of NSCLC; and H4 receptors
      may be a new therapeutic target for NSCLC treatment. 

PMID- 24447836
TI  - Catch the Ta wave: a source of ST-segment elevation.

PMID- 24447837
TI  - Thyroid bruit and the underlying 'inferno'.

PMID- 24447835
TI  - Investigation of inhalation anthrax case, United States.
AB  - Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax
      is enzootic. Despite an extensive multi-agency investigation, the specific source
      was not detected, and no additional related human or animal cases were found.
      Although rare, inhalation anthrax can occur naturally in the United States. 

PMID- 24447838
TI  - In-center hemodialysis attendance: patient perceptions of risks, barriers, and
      recommendations.
AB  - Missed hemodialysis treatments lead to increased morbidity and mortality in the
      end-stage renal disease population. Little is known about why patients have
      difficulty attending their scheduled in-center dialysis treatments.
      Semistructured interviews with 15 adherent and 15 nonadherent hemodialysis
      patients were conducted to determine patients' attitudes about dialysis, health
      beliefs and risk perception regarding missed treatments, barriers and
      facilitators to hemodialysis attendance, and recommendations to improve the
      system to facilitate dialysis attendance. Average time on dialysis was 2.5 years
      for the nonadherent group and 7.3 years in the adherent group. In both groups,
      patients felt that dialysis is life-saving and a necessity. A substantial number
      of patients in both groups understood that missing hemodialysis treatments is
      dangerous and several patients could clearly communicate the risk of skipping.
      The most common barriers to hemodialysis were inadequate or unreliable
      transportation (mentioned in both groups) and a lack of motivation to get to
      dialysis or that dialysis is not a priority (typically mentioned by the
      nonadherent group). Facilitators to hemodialysis attendance included explanations
      from the health care team regarding the risk of skipping and relationships with
      other dialysis patients. Patient recommendations to improve dialysis attendance
      included continued education about the risk of poor attendance and more
      accessible transportation. Patients did not feel that home dialysis would improve
      adherence. Hemodialysis patients must adhere to a complex and burdensome regimen.
      Through the elucidation of barriers and facilitators to hemodialysis attendance
      and through specific patient recommendations, at least three interventions may be
      further investigated to improve hemodialysis attendance: Improvement of the
      transportation system, education and supportive encouragement from the health
      care team, and peer support mentorship. 

PMID- 24447839
TI  - Effects of Kampo on functional gastrointestinal disorders.
AB  - This article reviews the effectiveness of Kampo (traditional Japanese herbal
      medicine) in the treatment of functional gastrointestinal disorders, especially
      functional dyspepsia (FD) and irritable bowel syndrome (IBS). The results of four
      randomized, controlled trials (RCTs) suggested the usefulness of rikkunshito in
      relieving the subjective symptoms of patients with FD. Rikkunshito significantly
      improved not only gastric symptoms, such as epigastiric discomfort, but also
      extra-gastric symptoms, such as general fatigue, when compared with control
      drugs. The therapeutic effects of rikkunshito were more evident when it was
      prescribed to patients with "kyosho", i.e., low energy. Two RCTs suggested the
      efficacy of keishikashakuyakuto for IBS.Basic research studies have demonstrated
      that these Kampo medicines have multiple sites of action to improve subjective
      symptoms. For example, rikkunshito improves gastric motility dysfunction,
      including impaired adaptive relaxation and delayed gastric emptying, gastric
      hypersensitivity, and anorexia via facilitation of ghrelin secretion. It also
      exhibits anti-stress effects, i.e., it attenuates stress-induced exacerbation of
      gastric sensation and anorexia, as well as the hypothalamic-pituitary
      adrenocortical axis and sympathetic activation. Keishikashakuyakuto exhibited not
      only an antispasmodic effect on intestinal smooth muscle, but also antidepressant
      like effects. Case series suggest that other Kampo prescriptions are also
      effective for FD and IBS. However, further studies are necessary to evaluate
      their efficacy. 

PMID- 24447840
TI  - Clock gene Per1 regulates the production of CCL2 and interleukin-6 through p38,
      JNK1 and NF-kappaB activation in spinal astrocytes.
AB  - It has been previously reported that spinal clock genes controlled under
      circadian rhythm contribute to the regulation of astrocytic function, which in
      turn is involved in diverse processes such as nociceptive transduction and the
      induction of inflammation. However, how clock genes expressed in spinal cord
      astrocytes are associated with the modulation of the inflammatory response is
      poorly understood. In the current study, the role of Period1 (Per1), one of clock
      genes, in the expression of chemokine (C-C motif) ligand 2 (CCL2) and interleukin
      6 (IL-6), which are typical pro-inflammatory mediators produced by spinal
      astrocytes, was investigated. It was found that the knockdown of Per1 by using
      RNA interference led to a significant increase of the expression of CCL2 and IL-6
      in cultured rat spinal astrocytes. Moreover, the silencing of the Per1 gene also
      increased the phosphorylation of p38, c-Jun N-terminal kinase (JNK) 1 and
      IkappaBalpha, and led to the translocation of p65 from the cytosol to the
      nucleus. The induction of CCL2 and IL-6 was significantly inhibited by treatment
      with the inhibitors of p38, JNK, and NF-kappaB. By contrast, the overexpression
      of PER1 by transfection vector significantly blocked the expression of CCL2 and
      IL-6, and the activation of p38, JNK, and NF-kappaB. Together, these results
      suggest that down-regulation of Per1 induced the phosphorylation of p38 and JNK1
      and the subsequent activation of NF-kappaB, and that these events contribute to
      neuroinflammatory state in the spinal cord via the induction of the release of
      inflammatory mediators. 

PMID- 24447842
TI  - Toward a proper estimation of phase-amplitude coupling in neural oscillations.
AB  - BACKGROUND: The phase-amplitude coupling (PAC) between distinct neural
      oscillations is critical to brain functions that include cross-scale
      organization, selection of attention, routing the flow of information through
      neural circuits, memory processing and information coding. Several methods for
      PAC estimation have been proposed but the limitations of PAC estimation as well
      as the assumptions about the data for accurate PAC estimation are unclear. NEW
      METHOD: We define boundary conditions for standard PAC algorithms and propose
      "oscillation-triggered coupling" (OTC), a parameter-free, data-driven algorithm
      for unbiased estimation of PAC. OTC establishes a unified framework that treats
      individual oscillations as discrete events for estimating PAC from a set of
      oscillations and for characterizing events from time windows as short as a single
      modulating oscillation. RESULTS: For accurate PAC estimation, standard PAC
      algorithms require amplitude filters with a bandwidth at least twice the
      modulatory frequency. The phase filters must be moderately narrow-band,
      especially when the modulatory rhythm is non-sinusoidal. The minimally
      appropriate analysis window is ~10s. We then demonstrate that OTC can
      characterize PAC by treating neural oscillations as discrete events rather than
      continuous phase and amplitude time series. COMPARISON WITH EXISTING METHODS:
      These findings show that in addition to providing the same information about PAC
      as the standard approach, OTC facilitates characterization of single oscillations
      and their sequences, in addition to explaining the role of individual
      oscillations in generating PAC patterns. CONCLUSIONS: OTC allows PAC analysis at
      the level of individual oscillations and therefore enables investigation of PAC
      at the time scales of cognitive phenomena.

PMID- 24447843
TI  - The distribution of intraocular pressure and associated systemic factors in a
      Korean population: the Korea National Health and Nutrition Examination Survey.
AB  - PURPOSE: To investigate the distribution of intraocular pressure (IOP) and its
      associated factors in a large Korean population based on the data from the
      nationwide cross-sectional survey. METHODS: We obtained 2009-2010 data from the
      Korea National Health and Nutrition Examination Survey (KNHANES) (n = 17 901).
      After excluding individuals under 19 years of age, a total of 13 431 subjects
      were enrolled. All participants completed a comprehensive questionnaire and
      underwent an ocular examination including measurement of IOP by Goldmann
      applanation tonometry, as well as a systemic evaluation including blood pressure
      measurements, anthropometry and blood tests. RESULTS: The mean IOP in the right
      eye was 13.99 +/- 2.75 mmHg, and in the left eye, 13.99 +/- 2.75 mmHg,
      representing no significant bilateral difference. There was, however, a
      significant difference between males (14.19 +/- 2.78 mmHg) and females (13.79 +/-
      2.70 mmHg) (p < 0.001). Multiple regression analysis revealed that higher IOP was
      significantly correlated with male sex, higher myopic refractive error, higher
      body mass index, higher systolic blood pressure, higher fasting plasma glucose
      and higher total cholesterol (all p < 0.05). On the other hand, age, histories of
      smoking or migraine or cold hands/feet were not significantly correlated with IOP
      (all p > 0.05). CONCLUSIONS: In the general Korean population, IOP increases with
      male sex and increasing myopia. Further, IOP is significantly correlated with
      systemic factors relating to cardiovascular disease and metabolic syndrome.

PMID- 24447844
TI  - A systematic review of interactive multimedia interventions to promote children's
      communication with health professionals: implications for communicating with
      overweight children.
AB  - BACKGROUND: Interactive multimedia is an emerging technology that is being used
      to facilitate interactions between patients and health professionals. The purpose
      of this review was to identify and evaluate the impact of multimedia
      interventions (MIs), delivered in the context of paediatric healthcare, in order
      to inform the development of a MI to promote the communication of dietetic
      messages with overweight preadolescent children. Of particular interest were the
      effects of these MIs on child engagement and participation in treatment, and the
      subsequent effect on health-related treatment outcomes. METHODS: An extensive
      search of 12 bibliographic databases was conducted in April 2012. Studies were
      included if: one or more child-participant was 7 to 11-years-of-age; a MI was
      used to improve health-related behaviour; child-participants were diagnosed with
      a health condition and were receiving treatment for that condition at the time of
      the study. Data describing study characteristics and intervention effects on
      communication, satisfaction, knowledge acquisition, changes in self-efficacy,
      healthcare utilisation, and health outcomes were extracted and summarised using
      qualitative and quantitative methods. RESULTS: A total of 14 controlled trials,
      published between 1997 and 2006 met the selection criteria. Several MIs had the
      capacity to facilitate engagement between the child and a clinician, but only one
      sought to utilise the MI to improve communication between the child and health
      professional. In spite of concerns over the quality of some studies and small
      study populations, MIs were found useful in educating children about their
      health, and they demonstrated potential to improve children's health-related self
      efficacy, which could make them more able partners in face-to-face communications
      with health professionals. CONCLUSIONS: The findings of this review suggest that
      MIs have the capacity to support preadolescent child-clinician communication, but
      further research in this field is needed. Particular attention should be given to
      designing appropriate MIs that are clinically relevant.

PMID- 24447845
TI  - Post-natal induction of PGC-1alpha protects against severe muscle dystrophy
      independently of utrophin.
AB  - BACKGROUND: Duchenne muscle dystrophy (DMD) afflicts 1 million boys in the US and
      has few effective treatments. Constitutive transgenic expression of the
      transcriptional coactivator peroxisome proliferator-activated receptor gamma
      coactivator (PGC)-1alpha improves skeletal muscle function in the murine "mdx"
      model of DMD, but how this occurs, or whether it can occur post-natally, is not
      known. The leading mechanistic hypotheses for the benefits conferred by PGC
      1alpha include the induction of utrophin, a dystrophin homolog, and/or induction
      and stabilization of the neuromuscular junction. METHODS: The effects of
      transgenic overexpression of PGC-1beta, a homolog of PGC-1alpha in mdx mice was
      examined using different assays of skeletal muscle structure and function. To
      formally test the hypothesis that PGC-1alpha confers benefit in mdx mice by
      induction of utrophin and stabilization of neuromuscular junction, PGC-1alpha
      transgenic animals were crossed with the dystrophin utrophin double knock out
      (mdx/utrn-/-) mice, a more severe dystrophic model. Finally, we also examined the
      effect of post-natal induction of skeletal muscle-specific PGC-1alpha
      overexpression on muscle structure and function in mdx mice. RESULTS: We show
      here that PGC-1beta does not induce utrophin or other neuromuscular genes when
      transgenically expressed in mouse skeletal muscle. Surprisingly, however, PGC
      1beta transgenesis protects as efficaciously as PGC-1alpha against muscle
      degeneration in dystrophin-deficient (mdx) mice, suggesting that alternate
      mechanisms of protection exist. When PGC-1alpha is overexpressed in mdx/utrn-/-
      mice, we find that PGC-1alpha dramatically ameliorates muscle damage even in the
      absence of utrophin. Finally, we also used inducible skeletal muscle-specific PGC
      1alpha overexpression to show that PGC-1alpha can protect against dystrophy even
      if activated post-natally, a more plausible therapeutic option. CONCLUSIONS:
      These data demonstrate that PGC-1alpha can improve muscle dystrophy post-natally,
      highlighting its therapeutic potential. The data also show that PGC-1alpha is
      equally protective in the more severely affected mdx/utrn-/- mice, which more
      closely recapitulates the aggressive progression of muscle damage seen in DMD
      patients. The data also identify PGC-1beta as a novel potential target, equally
      efficacious in protecting against muscle dystrophy. Finally, the data also show
      that PGC-1alpha and PGC-1beta protect against dystrophy independently of utrophin
      or of induction of the neuromuscular junction, indicating the existence of other
      mechanisms.

PMID- 24447847
TI  - Squamous cell carcinoma of the hand in solid organ transplant patients.

PMID- 24447846
TI  - Contribution of functional parameters to patient-rated outcomes after surgical
      treatment of distal radius fractures.
AB  - PURPOSE: Outcomes of distal radius fractures can be measured radiographically,
      functionally, or via patient-rated questionnaires, but previous studies report
      conflicting results regarding the relationship between these outcomes. Our
      specific aim was to explore the role that functional outcomes have in the score
      of the Michigan Hand Outcomes Questionnaire (MHQ), a patient-rated hand
      instrument. METHODS: We obtained data for 207 patients. Demographic information
      was collected as part of the MHQ. Function (wrist motion and grip and pinch
      strength) was assessed 3 and 6 months after fracture fixation. We applied linear
      regression analysis to determine each item's contribution to the total MHQ score.
      RESULTS: After we applied linear regression analysis, we determined that 3 months
      after fixation, all included factors contributed 37% of the MHQ score. Only the
      grip strength difference between the injured and uninjured hands was
      significantly associated, contributing 22% of the MHQ score. Six weeks and 6
      months after fixation, all included factors contributed 43% and 34%,
      respectively, of the MHQ score. No individual factors were significant
      contributors. CONCLUSIONS: Measured functional outcomes variables account for
      less than 40% of the total MHQ score. Identifying the unmeasured factors that
      make up the additional 60% of the total MHQ score would be beneficial in the
      continued examination of patient-rated outcomes. Furthermore, the use of multiple
      outcomes assessment modalities should be considered in any study measuring
      patient-rated outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 24447848
TI  - Finding a needle in the common carotid artery 3 years after ingestion.
AB  - A woman presented with an ischemic stroke involving the right middle cerebral
      artery. Investigations revealed a foreign body in the cervical area. It was
      identified as a metal needle, perforating the posterior pharyngeal wall and
      migrating into the right common carotid artery (CCA). Three years previously,
      this patient had complained of odynophagia, brought on by needle ingestion. Three
      days before her stroke, she had hematemesis, caused by migration of the needle
      into the CCA. The stroke was caused by migration of the thrombus. This type of
      event is rarely encountered in Europe. Early recognition could avoid dangerous
      vascular complications. 

PMID- 24447849
TI  - Synthesis and antimicrobial activities of novel 1,2,4-triazolo [3,4-a]
      phthalazine derivatives.
AB  - A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized
      in five steps from a common precursor, phthalic anhydride. Most of synthesized
      phthalazine derivatives showed inhibitory activity against Staphylococcus aureus.
      One of phthalazine derivatives 5l showed inhibitory activity against all tested
      bacterial and fungal strains. 

PMID- 24447850
TI  - Discovery of substituted lactams as novel dual orexin receptor antagonists.
      Synthesis, preliminary structure-activity relationship studies and efforts
      towards improved metabolic stability and pharmacokinetic properties. Part 1.
AB  - Starting from a thiazolidin-4-one HTS hit, a novel series of substituted lactams
      was identified and developed as dual orexin receptor antagonists. In this Letter,
      we describe our initial efforts towards the improvement of potency and metabolic
      stability. These investigations delivered optimized lead compounds with CNS drug
      like properties suitable for further optimization. 

PMID- 24447851
TI  - Pd-N-heterocyclic carbene catalyzed synthesis of piperidine alkene-alkaloids and
      their anti-cancer evaluation.
AB  - A facile synthesis of piperidine alkene-alkaloids including natural (+)
      Caulophyllumine B in high yields has been developed by Heck cross-coupling
      reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd
      NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction
      course. The synthesized piperidine alkene-alkaloids were evaluated for in vitro
      anti-cancer activity against a panel of human tumor cell lines of lung, breast
      and ovarian. Several of these piperidine alkene-alkaloids were found to possess
      highest growth inhibition activity than the standard drug cisplatin and support
      the concept to modulate drug receptor interaction. 

PMID- 24447852
TI  - Genetic characterization of coronaviruses from domestic ferrets, Japan.
AB  - We detected ferret coronaviruses in 44 (55.7%) of 79 pet ferrets tested in Japan
      and classified the viruses into 2 genotypes on the basis of genotype-specific
      PCR. Our results show that 2 ferret coronaviruses that cause feline infectious
      peritonitis-like disease and epizootic catarrhal enteritis are enzootic among
      ferrets in Japan. 

PMID- 24447853
TI  - Epidemiology of respiratory viruses in bronchoalveolar lavage samples in a
      tertiary hospital.
AB  - BACKGROUND: The prevalence of respiratory viruses in adults is largely
      underexplored, as most studies focus on children. Additionally, in severely ill
      or immunocompromised adults, where respiratory infections are mostly attributed
      to bacteria and fungi; respiratory viruses can lead to severe complications.
      OBJECTIVES: To evaluate the epidemiology of respiratory viruses in
      bronchoalveolar lavage fluid (BAL) specimens from patients with lower respiratory
      tract disease. The study population consisted of different groups including
      immunocompetent patients (control patients), solid organ transplant recipients,
      patients with haematological malignancies and other immunocompromised adults.
      STUDY DESIGN: A total of 134 BAL fluid specimens collected during 2009-2011 were
      retrospectively assessed with the new commercial multiplex real-time PCR FTD
      Respiratory 21 Plus((r)), targeting 18 different viruses and 2 atypical bacterial
      pathogens. RESULTS: Viral or atypical bacterial pathogens were detected in 29.1%
      of BAL fluid specimens. Coronaviruses were most prevalent (13.4%), followed by
      rhinoviruses (5.2%), RSV (4.5%) and bocaviruses (3.7%). Comparing the total
      number of viruses detected, a statistically significant difference was observed
      between the control group and patients with haematological malignancies (27.5%
      vs. 57.1%, p<0.05). CONCLUSION: In conclusion, our study highlights the high
      prevalence of respiratory viruses in BAL fluid specimens from adult patients with
      lower respiratory tract disease. The methods to be used should be sensitive and
      cover a wide range of potential pathogens. The specific patient population can
      also influence the detection rates of respiratory viruses.

PMID- 24447854
TI  - Risk factors for maternal mortality in a Tertiary Hospital in Kenya: a case
      control study.
AB  - BACKGROUND: Maternal mortality is high in Africa, especially in Kenya where there
      is evidence of insufficient progress towards Millennium Development Goal (MDG)
      Five, which is to reduce the global maternal mortality rate by three quarters and
      provide universal access to reproductive health by 2015. This study aims to
      identify risk factors associated with maternal mortality in a tertiary level
      hospital in Kenya. METHODS: A manual review of records for 150 maternal deaths
      (cases) and 300 controls was undertaken using a standard audit form. The sample
      included pregnant women aged 15-49 years admitted to the Obstetric and
      Gynaecological wards at the Moi Teaching and Referral Hospital (MTRH) in Kenya
      from January 2004 and March 2011. Logistic regression analysis was used to assess
      risk factors for maternal mortality. RESULTS: Factors significantly associated
      with maternal mortality included: having no education relative to secondary
      education (OR 3.3, 95% CI 1.1-10.4, p = 0.0284), history of underlying medical
      conditions (OR 3.9, 95% CI 1.7-9.2, p = 0.0016), doctor attendance at birth (OR
      4.6, 95% CI 2.1-10.1, p = 0.0001), having no antenatal visits (OR 4.1, 95% CI 1.6
      10.4, p = 0.0007), being admitted with eclampsia (OR 10.9, 95% CI 3.7-31.9, p <
      0.0001), being admitted with comorbidities (OR 9.0, 95% CI 4.2-19.3, p < 0.0001),
      having an elevated pulse on admission (OR 10.7, 95% CI 2.7-43.4, p = 0.0002), and
      being referred to MTRH (OR 2.1, 95% CI 1.0-4.3, p = 0.0459). CONCLUSIONS:
      Antenatal care and maternal education are important risk factors for maternal
      mortality, even after adjusting for comorbidities and complications. Antenatal
      visits can provide opportunities for detecting risk factors for eclampsia, and
      other underlying illnesses but the visits need to be frequent and timely.
      Education enables access to information and helps empower women and their spouses
      to make appropriate decisions during pregnancy.

PMID- 24447855
TI  - Attentional bias toward negative information in patients with fibromyalgia
      syndrome.
AB  - OBJECTIVE: In addition to central nervous sensitization, affect dysregulation
      constitutes an important factor in the pathogenesis of fibromyalgia syndrome
      (FMS). The present study is concerned with emotional influences on information
      processing in FMS. The hypothesis of attentional bias, i.e., selective processing
      of negatively connoted stimuli, was tested. METHODS: Twenty-seven female FMS
      patients and 34 healthy women undertook an emotional modification of the Stroop
      task. Subjects had to decide whether the colors of positive, negative, and
      neutral adjectives accorded with color words presented in black. Attentional bias
      was defined as delay in color naming of emotional words relative to neutral
      words. Affective and anxiety disorders, pain severity, as well as medication were
      considered as possible factors mediating the expected interference. RESULTS:
      Patients showed marked attentional bias, manifested in a greater response delay
      due to negative words compared with the control group. Among the clinical
      features, pain severity was most closely associated with the extent of the
      interference. While depression played only a subordinate role, anxiety and
      medication were without effect. CONCLUSIONS: The study provides evidence of
      emotionally driven selective attention in FMS. Attentional bias to negative
      information may play an important role in the vicious circle between negative
      affective state and pain augmentation. In the management of FMS pain, strategies
      aiming at conscious direction of attention may be helpful, e.g., imagery
      techniques or mindfulness training.

PMID- 24447856
TI  - Multiple subretinal fluid blebs after successful retinal detachment surgery:
      incidence, risk factors, and presumed pathophysiology.
AB  - PURPOSE: To investigate the incidence and the clinical factors associated with
      the occurrence of multiple subretinal fluid (SRF) blebs after successful
      rhegmatogenous retinal detachment (RD) repair. DESIGN: Retrospective,
      observational case series. METHODS: We retrospectively investigated the medical
      records of 185 eyes of 184 patients who had undergone successful RD surgery,
      either vitrectomy or scleral buckling. Each patient had undergone spectral-domain
      optical coherence tomography (SDOCT) combined with infrared reflectance (IR)
      imaging every 3 months postoperatively. We carefully examined postoperative SDOCT
      and fundus IR images, in an effort to identify any SRF blebs present. RESULTS:
      Multiple (>=3) SRF blebs were observed in 40 of 185 cases (21.6%). SRF blebs were
      first detected 1.7 +/- 1.8 months postoperatively. In 22 cases that could be
      fully followed up, SRF blebs were completely absorbed 13.1 +/- 6.1 months
      postoperatively. Multiple logistic regression analysis showed that only young age
      (<30 years) was significantly associated with the occurrence of multiple SRF
      blebs (odds ratio, 5.1; 95% confidence interval, 1.5-17.6; P = .010). Serial
      measurements of SRF bleb size using SDOCT showed that SRF bleb height was
      greatest at postoperative 2.9 +/- 0.9 months, while SRF bleb width tended to
      decrease gradually over time. The SRF blebs typically spared large retinal
      vessels. CONCLUSIONS: Multiple SRF blebs are commonly found after successful RD
      surgery, especially in young patients. The serial morphologic features evaluated
      in this study indicate that multiple SRF blebs may result from the active
      reattachment of retinal pigment epithelium and photoreceptors during the
      resolution of RD.

PMID- 24447857
TI  - Morphometric characterization of microglial phenotypes in human cerebral cortex.
AB  - BACKGROUND: Microglia can adopt different morphologies, ranging from a highly
      ramified to an amoeboid-like phenotype. Although morphological properties of
      microglia have been described in rodents, little is known about their fine
      features in humans. The aim of this study was to characterize the morphometric
      properties of human microglia in gray and white matter of dorsal anterior
      cingulate cortex (dACC), a region implicated in behavioral adaptation to
      neuroinflammation. These properties were compared to those of murine microglia in
      order to gain a better appreciation of the differences displayed by these cells
      across species. METHODS: Postmortem dACC samples were analyzed from 11
      individuals having died suddenly without any history of neuroinflammatory,
      neurodegenerative, nor psychiatric illness. Tissues were sectioned and
      immunostained for the macrophage marker Ionized calcium binding adaptor molecule
      1 (IBA1). Randomly selected IBA1-immunoreactive (IBA1-IR) cells displaying
      features corresponding to commonly accepted microglial phenotypes (ramified,
      primed, reactive, amoeboid) were reconstructed in 3D and all aspects of their
      morphologies quantified using the Neurolucida software. The relative abundance of
      each morphological phenotype was also assessed. Furthermore, adult mouse brains
      were similarly immunostained, and IBA1-IR cells in cingulate cortex were compared
      to those scrutinized in human dACC. RESULTS: In human cortical gray and white
      matter, all microglial phenotypes were observed in significant proportions.
      Compared to ramified, primed microglia presented an average 2.5 fold increase in
      cell body size, with almost no differences in branching patterns. When compared
      to the primed microglia, which projected an average of six primary processes, the
      reactive and amoeboid phenotypes displayed fewer processes and branching points,
      or no processes at all. In contrast, the majority of microglial cells in adult
      mouse cortex were highly ramified. This was also the case following a postmortem
      interval of 43 hours. Interestingly, the morphology of ramified microglia was
      strikingly similar between species. CONCLUSIONS: This study provides fundamental
      information on the morphological features of microglia in the normal adult human
      cerebral cortex. These morphometric data will be useful for future studies of
      microglial morphology in various illnesses. Furthermore, this first direct
      comparison of human and mouse microglia reveals that these brain cells are
      morphologically similar across species, suggesting highly conserved functions.

PMID- 24447858
TI  - Uptake kinetics of five hydrophobic organic pollutants in the earthworm Eisenia
      fetida in six different soils.
AB  - Hydrophobic organic contaminants in soils may pose toxicity or transfer to food
      chains after their uptake to soil biota. However, uptake data for earthworms are
      usually limited, as: (a) only fixed exposure times are studied instead of whole
      uptake kinetics and (b) studies including compounds with different environmental
      properties and more than two soils of different properties are quite rare. In our
      study, five persistent organic pollutants (phenanthrene, pyrene, lindane, p,p'
      dichlorodiphenyltrichloroethane (p,p'-DDT), and polychlorinated biphenyl congener
      No. 153 (PCB 153)) were added to six soils of a wide range of soil properties.
      Detailed kinetics of uptake to earthworms Eisenia fetida were measured. Results
      indicated that an equilibrium of concentrations for p,p'-DDT and PCB 153 was
      reached after 11 days of exposure in all soils. Uptake of phenanthrene, pyrene,
      and lindane was strongly influenced by the decrease in concentrations in the
      soils, resulting in peak-shaped accumulation curves. Only in soils with the
      highest total organic carbon content (7.9 and 20.2%), the equilibrium of lindane
      concentrations was achieved (after 17 and 5 days of exposure, respectively). We
      recommend calculating bioaccumulation factors as a ratio of the uptake and
      elimination rate constants to precise the risk assessment. 

PMID- 24447859
TI  - Particle concentration dynamics in the ventilation duct after an artificial
      release: for countering potential bioterrorist attack.
AB  - Ventilation duct serves as a potential target for bioterrorist attack.
      Understanding the dynamics of aerosolized harmful agents in the ventilation ducts
      provides the fundamentals for effective control and management, e.g., risk
      assessment. In this work, new models for predicting the concentration dynamics in
      the ventilation duct after a particle resuspension (representing the case that
      harmful agents are dosed when the ventilation is off and subsequently being
      turned on) or puff injection (representing the case that harmful agents are dosed
      when the ventilation is running) event were derived based on the mass balance
      model. The models were validated by a series of wind tunnel experiments. Indoor
      airborne particle concentration models were derived by incorporating the proposed
      ventilation duct models for resuspension and injection cases. The effects of
      resuspension and injection in the duct on indoor airborne particle concentration
      were examined by two hypothetical cases of Bacillus anthracis dosage using the
      derived models. For the same amount of BW agent dosage in the ventilation duct,
      the resuspension type release prolongs the exposure of harmful agents whereas the
      injection type release produces a higher peak concentration. 

PMID- 24447860
TI  - A new analytic expression for fast calculation of the transient near and far
      field of a rectangular baffled piston.
AB  - Essential to (cardiac) 3D ultrasound are 2D matrix array transducer technology
      and the associated (two-stage) beam forming. Given the large number of degrees of
      freedom and the complexity of this problem, simulation tools play an important
      role. Hereto, the impulse response (IR) method is commonly used. Unfortunately,
      given the large element count of 2D array transducers, simulation times become
      significant jeopardizing the efficacy of the design process. The aim of this
      study was therefore to derive a new analytical expression to more efficiently
      calculate the IR in order to speed up the calculation process. To compare
      accuracy and computation time, the reference and the proposed method were
      implemented in MATLAB and contrasted. For all points of observation tested, the
      IR with both methods was identical. The mean calculation time however reduced in
      average by a factor of 3.93+/-0.03 times. The proposed IR method therefore speeds
      up the calculation time of the IR of an individual transducer element while
      remaining perfectly accurate. This new expression will be particularly relevant
      for 2D matrix transducer design where computation times remain currently a bottle
      neck in the design process. 

PMID- 24447861
TI  - Kampo medicine for palliative care in Japan.
AB  - Kampo medicines are currently manufactured under strict quality controls. The
      Ministry of Health, Labour and Welfare of Japan has approved 148 Kampo formulas.
      There is increasing evidence for the efficacy of Kampo medicines, and some are
      used clinically for palliative care in Japan. The specific aim of this review is
      to evaluate the clinical use of Kampo medicines in palliative care in the
      treatment of cancer. The conclusions are as follows: Juzentaihoto inhibits the
      progression of liver tumors in a dose-dependent manner and contributes to long
      term survival. Hochuekkito has clinical effects on cachexia for genitourinary
      cancer and improves the QOL and immunological status of weak patients, such as
      postoperative patients. Daikenchuto increases intestinal motility and decreases
      the postoperative symptoms of patients with total gastrectomy with jejunal pouch
      interposition, suppresses postoperative inflammation following surgery for
      colorectal cancer, and controls radiation-induced enteritis. Rikkunshito
      contributes to the amelioration of anorectic conditions in cancer cachexia
      anorexia syndrome. Goshajinkigan and Shakuyakukanzoto reduce the neurotoxicity of
      patients with colorectal cancer who undergo oxaliplatin and FOLFOX (5
      fluorouracil/folinic acid plus oxaliplatin) therapy. Hangeshashinto has the
      effect of preventing and alleviating diarrhea induced by CPT-11(irinotecan) and
      combination therapy with S-1/CPT-11. O'rengedokuto significantly improves
      mucositis caused by anticancer agents. 

PMID- 24447862
TI  - Introduction to the NeuroImage special issue: "In vivo Brodmann mapping of the
      human brain".

PMID- 24447863
TI  - TREM-1 modulation during early stages of dengue virus infection.
AB  - Uncontrolled and intricate production of inflammatory factors is the
      characteristic feature of dengue infection. The triggering receptor expressed in
      myeloid cells-1 (TREM-1), expressed on the surface of monocytes and neutrophils,
      is capable of enhancing and regulating the inflammatory response via the
      production of different mediators in bacterial and viral infections. Here, both
      the expression of TREM-1 on human monocytes and neutrophils from peripheral blood
      of dengue infected individuals, as well as the levels of the soluble form of TREM
      1 (sTREM-1) in the sera of these patients were compared against healthy controls.
      A significant reduction of TREM-1 expression was observed in neutrophils during
      the first days of infection, followed by a gradual recovery throughout the course
      of infection. Also, sera from DENV-infected patients exhibited significantly
      higher sTREM-1 levels than healthy individuals. The difference was more
      pronounced during the first 5 days after the onset of symptoms. These findings
      highlight the dynamic process of TREM-1 expression during DENV infection. We
      hypothesized that increment of free sTREM-1 could be a compensatory mechanism
      aiming to counteract the inflammatory process elicited during DENV infection. 

PMID- 24447864
TI  - Correlation of cytokines and inducible nitric oxide synthase expression with
      prognostic factors in ovarian cancer.
AB  - The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6,
      IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological
      parameters of patients with primary ovarian malignancy. We prospectively
      evaluated 40 patients who underwent surgical treatment in accordance with pre
      established criteria and later confirmed diagnosis of ovarian cancer.
      Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha)
      and iNOS was performed. The evaluation of prognostic factors was performed using
      the Fisher's exact test. The significance level was less than 0.05. Histological
      grade 1 was significantly correlated with strong intensity for TNF-alpha
      (p=0.0028). In addition, early stages showed strong expression intensity of TNF
      alpha, but this was at the limit of significance (p=0.0525). Strong staining
      immunohistochemical IL5 was related to disease-free survival less than or equal
      to 24 months, suggesting that a factor of poor prognosis, but there was no
      statistical significance (p=0.1771). There was no statistical significance in
      relation at other cytokines studied. Therefore, immunohistochemical staining in
      strong intensity for TNF-alpha was related to histological grade 1 and early
      stages of ovarian cancer in our sample of patients. 

PMID- 24447866
TI  - Seeing things differently.

PMID- 24447865
TI  - In rheumatoid arthritis soluble CD30 ligand is present at high levels and induces
      apoptosis of CD30(+)T cells.
AB  - CD30 and CD30 ligand (CD30L) are members of TNF-receptor and TNF superfamilies
      respectively. CD30(+)T cells are increased in several diseases and interaction
      between CD30(+) and CD30L(+)T cells leads either to cell proliferation or
      apoptosis. In patients with rheumatoid arthritis (RA), soluble CD30 (sCD30)
      levels seem to reflect the recruitment of CD30(+)T cells into the inflamed joints
      and are predictive of a positive response to classical and biological
      immunosuppressive therapy. We have evaluated the presence of soluble CD30L
      (sCD30L) in the sera and synovial fluid of patients with RA and defined whether
      it binds surface CD30 molecule and is functionally active. We found high levels
      of sCD30L in sera and synovial fluid of RA patients; the molecule is shedded upon
      direct contact of CD30(+)/CD30L(+)T cells. Moreover sCD30L binds surface CD30
      constitutively expressed by Jurkat cell line. Finally recombinant sCD30L and sera
      from patients with high levels of sCD30L are able to inhibit CD30(+)T cell
      proliferation by inducing cell apoptosis. Our findings suggest that circulant
      sCD30L is functionally active and that it may favor persistence of active
      inflammation by inducing apoptosis of CD30(+)T cells, known to down-modulate
      inflammation in rheumatoid synovitis. 

PMID- 24447867
TI  - Sub-acute intravenous administration of silver nanoparticles in male mice alters
      Leydig cell function and testosterone levels.
AB  - The aim of this study was to determine whether short-term, in vivo exposure to
      silver nanoparticles (AgNPs) could be toxic to male reproduction. Low dose
      (1mg/kg/dose) AgNPs were intravenously injected into male CD1 mice over 12 days.
      Treatment resulted in no changes in body and testis weights, sperm concentration
      and motility, fertility indices, or follicle-stimulating hormone and luteinizing
      hormone serum concentrations; however, serum and intratesticular testosterone
      concentrations were significantly increased 15 days after initial treatment.
      Histologic evaluation revealed significant changes in epithelium morphology, germ
      cell apoptosis, and Leydig cell size. Additionally, gene expression analysis
      revealed Cyp11a1 and Hsd3b1 mRNA significantly upregulated in treated animals.
      These data suggest that AgNPs do not impair spermatogonial stem cells in vivo
      since treatment did not result in significant decreases in testis weight and
      sperm concentrations. However, AgNPs appear to affect Leydig cell function,
      yielding increasing testicular and serum testosterone levels. 

PMID- 24447868
TI  - [Giant abdominal pseudocyst: a rare complication of incisional hernia repair with
      mesh].

PMID- 24447869
TI  - [Surgery as a scientific discipline and the IDEAL Collaboration].

PMID- 24447870
TI  - Spontaneous rupture of a hepatocellular carcinoma: is a liver transplant
      indicated?

PMID- 24447871
TI  - [25 years of laparoscopic surgery in Spain].
AB  - INTRODUCTION: The introduction of laparoscopic surgery (LS) can be considered the
      most important advancement in our specialty in the past 25 years. Despite its
      advantages, implementation and consolidation has not been homogenous, especially
      for advanced techniques. The aim of this study was to analyse the level of
      development and use of laparoscopic surgery in Spain at the present time and its
      evolution in recent years. MATERIAL AND METHODS: During the second half of 2012 a
      survey was developed to evaluate different aspects of the implementation and
      development of LS in our country. The survey was performed using an electronic
      questionnaire. RESULTS: The global response rate was 16% and 103 heads of
      Department answered the survey. A total of 92% worked in the public system. A
      total of 99% perform basic laparoscopic surgery and 85,2% advanced LS. Most of
      the responders (79%) consider that the instruments they have available for LS are
      adequate and 71% consider that LS is in the right stage of development in their
      environment. CONCLUSIONS: Basic laparoscopic surgery has developed in our country
      to be considered the standard performed by most surgeons, and forms part of the
      basic surgical training of residents. With regards to advanced LS, although it is
      frequently used, there are still remaining areas of deficit, and therefore,
      opportunities for improvement.

PMID- 24447872
TI  - Psychological changes in morbidly obese patients after sleeve gastrectomy.
AB  - BACKGROUND: The aim of this study is to observe the psychological changes at one
      year postop in a group of patients undergoing laparoscopic vertical sleeve
      gastrectomy (GVL) and multidisciplinary follow- up. METHODS: A total of 46
      patients with a BMI-35 or higher, who were selected for GVL, completed
      psychological testing. After GVL surgery, patients received psychological,
      nutritional, and medical attention during 12 months, and they retook the same
      tests. RESULTS: Psychological tests showed an improvement on almost all scales
      tested, except perfectionism. The most significant change was in the benchmark
      for Eating Disorders with an improvement of 89% for bulimia (P<.01), and 55% for
      body dissatisfaction (P<.01) and ineffectiveness (P<.01). In quality of life
      there was an improvement of 57% in the change in health status (P<.01).
      CONCLUSION: During our study, a protocol involving GVL and multidisciplinary
      follow-ups seems proved to be an effective intervention for improving bulimic
      symptoms and quality of living. The results of these psychological changes are
      similar to Roux-en-Y Gastric bypass but different to vertical banded gastroplasty
      or adjustable gastric band, according to previous studies. However, long-term
      studies are necessary to confirm this trend.

PMID- 24447873
TI  - Maternal deaths in eastern Indonesia: 20 years and still walking: an ethnographic
      study.
AB  - BACKGROUND: The delays in receiving adequate emergency maternal care described by
      Thaddeus and Maine twenty years ago are still occurring, as exemplified in this
      study of cases of maternal deaths in a subdistrict in rural eastern Indonesia.
      METHODS: An ethnographic design was conducted, recruiting eleven families who
      reported on cases of maternal deaths in one sub-district of Indonesia, as well as
      assessing the geographical and cultural context of the villages. Traditional
      birth attendants and village leaders provided information to the research team
      which was thematically and contextually analysed. RESULTS: Two stages to the
      first and second delays have been differentiated in this study. First, delays in
      the decision to seek care comprised time taken to recognise (if at all) that an
      emergency situation existed, followed by time taken to reach a decision to
      request care. The decision to request care resided variously with the family or
      cadre. Second, delays in reaching care comprised time taken to deliver the
      request for help and then time for help to arrive. A phone was not available to
      request care in many cases and so the request was delivered by walking or
      motorbike. In two cases where the decision to seek care and the delivery of the
      request happened in a timely way, help was delayed because the midwife and
      ambulance respectively were unavailable. CONCLUSIONS: This study, although a
      small sample, confirmed that either a single delay or a sequence of delays can
      prove fatal. Delays were determined by both social and geographic factors, any of
      which alone could be limiting. Initiatives to improve maternal health outcomes
      need to address multiple factors: increased awareness of equitable access to
      maternal health care, village preparedness for emergency response, improved
      access to telecommunications and geographic access.

PMID- 24447874
TI  - Preface for dynamic and ultrastructure of bioenergetic membranes and their
      components.

PMID- 24447875
TI  - Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney
      transplant patients.
AB  - BACKGROUND & AIMS: Detection of hepatitis C virus (HCV) RNA in peripheral blood
      mononuclear cells (PBMC) and/or hepatocytes in absence of HCV RNA in serum,
      designated as 'occult HCV infection', has been a matter of controversy in recent
      years. We investigated for the first time the prevalence of occult HCV infection
      in large cohorts of chronic hemodialysis (CHD) and kidney transplant (KTx)
      patients. METHODS: We enrolled 417 CHD patients, 417 KTx recipients and 2 control
      groups - 25 anti-HCV (antibody against HCV)-positive and HCV RNA-positive
      patients with chronic hepatitis C, and 40 anti-HCV-, HCV RNA-, and HBsAg-negative
      healthy subjects. HCV RNA was tested in serum and PBMC using a sensitive
      commercial assay. RESULTS: In CHD patients, the prevalence of anti-HCV was 3.6%
      (15/417) and of positive serum HCV RNA 2.4% (10/417). HCV RNA was detected in
      PBMC in 1/407 (0.25%) HCV serum RNA-negative patients ("occult HCV infection").
      In KTx recipients, prevalence of anti-HCV was 4.8% (20/417) and of positive serum
      HCV RNA 4.6% (19/417). Occult HCV infection was found in 2/398 (0.5%) serum HCV
      RNA-negative patients. On a mean longitudinal follow-up of 30months of the 3
      patients with occult HCV infection, there was no clinical or virological evidence
      of HCV infection. CONCLUSIONS: The prevalence of occult HCV infection was very
      low in our CHD and KTx patients, and it did not appear to be clinically relevant.
      Further studies in geographic populations with high HCV endemicity are required
      to clarify the significance of occult HCV infection in these patient groups.

PMID- 24447877
TI  - Crimean-Congo hemorrhagic fever virus, Greece.
AB  - Seroprevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) is high in some
      regions of Greece, but only 1 case of disease has been reported. We used 4
      methods to test 118 serum samples that were positive for CCHFV IgG by commercial
      ELISA and confirmed the positive results. A nonpathogenic or low-pathogenicity
      strain may be circulating. 

PMID- 24447878
TI  - An "in vitro" experimental model to predict the mechanical behavior of
      macroporous scaffolds implanted in articular cartilage.
AB  - A model is proposed to assess mechanical behavior of tissue engineering scaffolds
      and predict their performance "in vivo" during tissue regeneration. To simulate
      the growth of tissue inside the pores of the scaffold, the scaffold is swollen
      with a Poly (Vinyl alcohol) solution and subjected to repeated freezing and
      thawing cycles. In this way the Poly (Vinyl alcohol) becomes a gel whose
      stiffness increases with the number of freezing and thawing cycles. Mechanical
      properties of the construct immersed in water are shown to be determined, in
      large extent, by the water mobility constraints imposed by the gel filling the
      pores. This is similar to the way that water mobility determines mechanical
      properties of highly hydrated tissues, such as articular cartilage. As a
      consequence, the apparent elastic modulus of the scaffold in compression tests is
      much higher than those of the empty scaffold or the gel. Thus this experimental
      model allows assessing fatigue behavior of the scaffolds under long-term dynamic
      loading in a realistic way, without recourse to animal experimentation. 

PMID- 24447876
TI  - Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis.
AB  - BACKGROUND & AIMS: Terlipressin and albumin is the standard of care for classical
      type-1 hepatorenal syndrome (HRS) not associated with active infections. However,
      there is no information on efficacy and safety of this treatment in patients with
      type-1 HRS associated with sepsis. Study aim was to investigate the effects of
      early treatment with terlipressin and albumin on circulatory and kidney function
      in patients with type-1 HRS and sepsis and assess factors predictive of response
      to therapy. METHODS: Prospective study in 18 consecutive patients with type-1 HRS
      associated with sepsis. RESULTS: Treatment was associated with marked improvement
      in arterial pressure and suppression of the high levels of plasma renin activity
      and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved
      in 12/18 patients (67%) and was associated with improved 3-month survival
      compared to patients without response. Non-responders had significantly lower
      baseline heart rate, poor liver function tests, slightly higher serum creatinine,
      and higher Child-Pugh and MELD scores compared to responders. Interestingly, non
      responders had higher values of CLIF-SOFA score compared to responders (14+/-3
      vs. 8+/-1, respectively p<0.001), indicating greater severity of acute-on-chronic
      liver failure (ACLF). A CLIF-SOFA score ?11 had 92% sensitivity and 100%
      specificity in predicting no response to therapy. No significant differences were
      observed between responders and non-responders in baseline urinary kidney
      biomarkers. Treatment was safe and no patient required withdrawal of
      terlipressin. CONCLUSIONS: Early treatment with terlipressin and albumin in
      patients with type-1 HRS associated with sepsis is effective and safe. Patients
      with associated severe ACLF are unlikely to respond to treatment.

PMID- 24447879
TI  - Association study of human leukocyte antigen-DRB1 alleles with rheumatoid
      arthritis in Algerian patients.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory and
      multifactorial disease. Genetic predisposition seems to play an important role.
      The aim of this study is to explore the relationship between human leukocyte
      antigen (HLA)-DRB1 alleles and susceptibility, clinical and biological features
      of RA in an Algerian patient population. METHODS: Using polymerase chain reaction
      - sequence specific primers (SSP), 134 RA patients and 132 healthy controls were
      genotyped for HLA-DRB1 and HLA-DRB1*04 subtypes. RESULTS: HLA-DRB1*04 was found
      to have increased frequency in the RA group compared to controls (P < 0.001, OR =
      3.14), and was associated with anti-citrullinated protein antibodies positivity
      (ACPA) (P = 0.01, OR = 2.35). In contrast, HLA-DRB1*07 was found to have a
      decreased frequency in patients compared to controls (P = 0.003, OR = 0.44) and
      significant decrease was observed in patients with the rheumatoid factor (RF)
      positivity subgroup (P = 0.009, OR = 0.29). HLA-DRB1*04:05 was associated with RA
      (P = 0.005, OR = 3.41), whereas, HLA-DRB1*04:02 showed a protective effect
      against RA (P = 0.003, OR = 0.20). CONCLUSIONS: HLA-DRB1*04 was associated with
      increased risk for RA and ACPA positivity, while HLA-DRB1*07 was associated with
      reduced risk for RA and RF synthesis in Algerian patients.

PMID- 24447882
TI  - Molecular evidence for the monophyly of flatfishes (Carangimorpharia:
      Pleuronectiformes).
AB  - Proliferation of phylogenetic studies based on poor taxonomic sampling or
      insufficient molecular evidence usually leads to conflicting results. As a
      consequence, advancement of systematic knowledge yields to confusion. The problem
      is exacerbated for taxonomic groups with historically difficult resolution of
      evolutionary relationships such as the flatfishes. Molecular evidence to support
      monophyly for this emblematic group of fishes and their interrelationships has
      been elusive, and a recent paper published in this journal went as far as to
      claim that flatfish monophyly can be rejected with molecular data, implying that
      the asymmetric body plan unique to these fishes had two independent origins. A
      reanalysis of this evidence suggests the contrary and combination of the new data
      with existing datasets unequivocally supports the monophyly of this group based
      on analyses of concatenated data as well as species tree approaches. Resolution
      of difficult phylogenetic problems requires analysis of larger datasets with
      adequate taxonomic coverage and sound hypothesis-testing procedures.
      Proliferation of partial studies claiming extraordinary results should be avoided
      in order to advance the field of molecular phylogenetics. 

PMID- 24447880
TI  - Chronic neuroinflammation and cognitive impairment following transient global
      cerebral ischemia: role of fractalkine/CX3CR1 signaling.
AB  - Although neuroinflammation has been studied extensively in animal models of
      cerebral ischemia, their contrasting functions are still not completely
      understood. A major participant in neuroinflammation is microglia and microglial
      activation usually regulated by the chemokine CX3CL1 (fractalkine) and its
      receptor, CX3CR1. Here, we examined the involvement of CX3CR1 on ischemia-induced
      chronic neuroinflammation and cognitive function using small interfering RNA
      (siRNA). Forty adult male Wistar rats were included in the study and received
      either ischemia or sham surgery then were randomized to receive either CX3CR1
      siRNA or scrambled RNA as control starting at 7 days after reperfusion.
      Behavioral testing commenced 28 days after siRNA delivery and all rats were
      euthanized after behavioral testing. Our data showed that: (i) transient global
      cerebral ischemia significantly decreased fractalkine/CX3CR1 signaling in the
      hippocampus; (ii) inhibition of CX3CR1 function exacerbated the ischemia-induced
      chronic increase in microglial activation and pro-inflammatory cytokine levels;
      (iii) inhibition of CX3CR1 function worsened ischemia-induced chronic cognitive
      impairment; (iv) inhibition of CX3CR1 function in sham rats resulted in increased
      IL-1beta expression and impaired behavioral performance. However, no significant
      effect of CX3CR1 on ischemia-induced neurodegeneration was seen. The present
      study provides important insight to understanding the involvement of CX3CR1 in
      chronic neuroinflammation and cognitive impairment. 

PMID- 24447883
TI  - [The ethical challenges of the obstetrician].

PMID- 24447884
TI  - Novel large deletion in the ACTA1 gene in a child with autosomal recessive
      nemaline myopathy.
AB  - Nemaline myopathy (NM) is a genetically and clinically heterogeneous disorder
      resulting from a disruption of the thin filament proteins of the striated muscle
      sarcomere. The disorder is typically characterized by muscle weakness including
      the face, neck, respiratory, and limb muscles and is clinically classified based
      on the age of onset and severity. Mutations in the ACTA1 gene contribute to a
      significant proportion of NM cases. The majority of ACTA1 gene mutations are
      missense mutations causing autosomal dominant NM by producing an abnormal
      protein. However, approximately 10% of ACTA1 gene mutations are associated with
      autosomal recessive NM; these mutations are associated with loss of protein
      function. We report the first case of a large deletion in the ACTA1 gene
      contributing to autosomal recessive NM. This case illustrates the importance of
      understanding disease mechanisms at the molecular level to accurately infer the
      inheritance pattern and potentially aid with clinical management. 

PMID- 24447885
TI  - Perinatal smoking and depression in women with concurrent substance use.
AB  - OBJECTIVE: The purpose of this report was to examine the course of smoking among
      pregnant women with concurrent substance use, and to assess the impact of
      depression on smoking. METHODS: Data were gathered as part of a randomized
      controlled trial assessing the efficacy of substance abuse treatment in pregnant
      women. Women (n=176) were recruited before 28 completed weeks of pregnancy, and
      followed until 3months postpartum. Depression was assessed using the Inventory of
      Depressive Symptomatology and the MINI Neuropsychiatric Interview. Our outcome
      was the average number of cigarettes smoked per day. Linear mixed effects
      regression was used to measure differential changes in smoking. RESULTS: 66% of
      women smoked in the three months before pregnancy, 42% of pre-pregnancy smokers
      achieved abstinence before delivery and 60% of the baseline cohort smoked
      postpartum. Smoking did not differ significantly between depressed and non
      depressed groups. After delivery both groups increased smoking at similar rates.
      CONCLUSION: Smoking was common among our cohort of pregnant women with a history
      of substance use. Women were able to discontinue or decrease smoking during
      pregnancy, but were likely to resume or increase smoking postpartum. Having
      clinically significant depressive symptoms or a diagnosis of depression did not
      have an obvious effect on smoking behaviors.

PMID- 24447886
TI  - A web-based, health promotion program for adolescent girls and their mothers who
      reside in public housing.
AB  - This study tested a brief web-based, family-involvement health promotion program
      aimed at drug use, physical activity, and nutrition for adolescent girls, aged 10
      to 12 years, who reside in public housing. Separately, girls (n=67) and their
      mothers (n=67) completed baseline measures online. Following baseline, 36
      randomly assigned mother-daughter dyads jointly completed a 3-session, health
      promotion program online. Subsequently, all girls and mothers separately
      completed posttest and 5-month follow-up measures. Attrition at posttest and 5
      month follow-up measures was 3% and 9%, respectively. At posttest, intervention
      arm girls, relative to control-arm girls, reported greater mother-daughter
      communication and parental monitoring. Intervention-arm mothers reported greater
      mother-daughter communication and closeness as well as increased vegetable intake
      and physical activity. At 5-month follow-up, intervention-arm girls and mothers,
      relative to those in the control arm, reported greater levels of parental
      monitoring. Intervention-arm girls also reported greater mother-daughter
      communication and closeness, reduced stress, greater refusal skills, and
      increased fruit intake. Findings indicate the potential of a brief, web-based
      program to improve the health of low-income girls and their mothers.

PMID- 24447887
TI  - [Severe colitis due to cytomegalovirus in a patient with idiopathic CD4
      lymphocytopenia].

PMID- 24447888
TI  - [Giant inflammatory fibroid polyp of the stomach: Endoscopic management].

PMID- 24447889
TI  - [Gastrointestinal bleeding due to a small bowel pyogenic granuloma].

PMID- 24447891
TI  - [Fulminant hepatitis due to herpes simplex virus in an immunocompetent patient.
      Differential diagnosis with acute cholecystitis].

PMID- 24447890
TI  - [Abdominal tuberculosis diagnosed by endoscopy in a patient under treatment with
      biological agents].

PMID- 24447892
TI  - [Readmission in general surgery: is there association with patient's age?].

PMID- 24447893
TI  - Protein and miRNA profiling of radiation-induced skin injury in rats: the
      protective role of peroxiredoxin-6 against ionizing radiation.
AB  - Radiation-induced skin injury is a serious concern during radiotherapy. However,
      the molecular mechanism underlying the pathogenesis of radiation-induced skin
      injury has not been extensively reported. Most biological functions are performed
      and regulated by proteins and noncoding RNAs, including microRNAs (miRNAs). The
      interplay between mRNA and miRNA has been implicated in disease initiation and
      progression. Technical advances in genomics and proteomics have enabled the
      exploration of the etiology of diseases and have the potential to broaden our
      understanding of the molecular pathogenesis of radiation-induced skin injury. In
      this study, we compared the protein and miRNA expression in rat skin irradiated
      with a 45-Gy electron beam with expression from adjacent normal tissues. We found
      24 preferentially expressed proteins and 12 dysregulated miRNAs in irradiated
      skin. By analyzing the protein and miRNA profiles using bioinformatics tools, we
      identified a possible interaction between miR-214 and peroxiredoxin-6 (PRDX-6).
      Next, we investigated the expression of PRDX-6 and the consequences of its
      dysregulation. PRDX-6 is suppressed by radiation-inducible miR-214 and is
      involved in the pathogenesis of radiation-induced skin injury. Overexpression of
      PRDX-6 conferred radioresistance on cells, decreased cell apoptosis, and
      preserved mitochondrial integrity after radiation exposure. In addition, in vivo
      transfection with PRDX-6 reduced radiation-induced reactive oxygen species and
      the malondialdehyde concentration and ameliorated radiation-induced skin damage
      in rats. Our present findings illustrate the molecular changes during radiation
      induced skin injury and the important role of PRDX-6 in ameliorating this damage
      in rats. 

PMID- 24447894
TI  - The kinetics of the reaction of nitrogen dioxide with iron(II)- and iron(III)
      cytochrome c.
AB  - The reactions of NO2 with both oxidized and reduced cytochrome c at pH 7.2 and
      7.4, respectively, and with N-acetyltyrosine amide and N-acetyltryptophan amide
      at pH 7.3 were studied by pulse radiolysis at 23  degrees C. NO2 oxidizes N
      acetyltyrosine amide and N-acetyltryptophan amide with rate constants of (3.1+/
      0.3)*10(5) and (1.1+/-0.1)*10(6) M(-1) s(-1), respectively. With
      iron(III)cytochrome c, the reaction involves only its amino acids, because no
      changes in the visible spectrum of cytochrome c are observed. The second-order
      rate constant is (5.8+/-0.7)*10(6) M(-1) s(-1) at pH 7.2. NO2 oxidizes
      iron(II)cytochrome c with a second-order rate constant of (6.6+/-0.5)*10(7) M(-1)
      s(-1) at pH 7.4; formation of iron(III)cytochrome c is quantitative. Based on
      these rate constants, we propose that the reaction with iron(II)cytochrome c
      proceeds via a mechanism in which 90% of NO2 oxidizes the iron center directly
      most probably via reaction at the solvent-accessible heme edge-whereas 10%
      oxidizes the amino acid residues to the corresponding radicals, which, in turn,
      oxidize iron(II). Iron(II)cytochrome c is also oxidized by peroxynitrite in the
      presence of CO2 to iron(III)cytochrome c, with a yield of ~60% relative to
      peroxynitrite. Our results indicate that, in vivo, NO2 will attack preferentially
      the reduced form of cytochrome c; protein damage is expected to be marginal, the
      consequence of formation of amino acid radicals on iron(III)cytochrome c.

PMID- 24447895
TI  - Human immunity in vitro - solving immunogenicity and more.
AB  - It has been widely recognised that the phylogenetic distance between laboratory
      animals and humans limits the former's predictive value for immunogenicity
      testing of biopharmaceuticals and nanostructure-based drug delivery and adjuvant
      systems. 2D in vitro assays have been established in conventional culture plates
      with little success so far. Here, we detail the status of various 3D approaches
      to emulate innate immunity in non-lymphoid organs and adaptive immune response in
      human professional lymphoid immune organs in vitro. We stress the tight
      relationship between the necessarily changing architecture of professional
      lymphoid organs at rest and when activated by pathogens, and match it with the
      immunity identified in vitro. Recommendations for further improvements of
      lymphoid tissue architecture relevant to the development of a sustainable
      adaptive immune response in vitro are summarized. In the end, we sketch a
      forecast of translational innovations in the field to model systemic innate and
      adaptive immunity in vitro. 

PMID- 24447896
TI  - The sleep lost.

PMID- 24447897
TI  - Centers for disease control and prevention expert panel meetings on prevention
      and treatment of anthrax in adults.
AB  - The Centers for Disease Control and Prevention convened panels of anthrax experts
      to review and update guidelines for anthrax postexposure prophylaxis and
      treatment. The panels included civilian and military anthrax experts and
      clinicians with experience treating anthrax patients. Specialties represented
      included internal medicine, pediatrics, obstetrics, infectious disease, emergency
      medicine, critical care, pulmonology, hematology, and nephrology. Panelists
      discussed recent patients with systemic anthrax; reviews of published,
      unpublished, and proprietary data regarding antimicrobial drugs and anthrax
      antitoxins; and critical care measures of potential benefit to patients with
      anthrax. This article updates antimicrobial postexposure prophylaxis and
      antimicrobial and antitoxin treatment options and describes potentially
      beneficial critical care measures for persons with anthrax, including clinical
      procedures for infected nonpregnant adults. Changes from previous guidelines
      include an expanded discussion of critical care and clinical procedures and
      additional antimicrobial choices, including preferred antimicrobial drug
      treatment for possible anthrax meningitis. 

PMID- 24447898
TI  - Trace-forward investigation of mice in response to lymphocytic choriomeningitis
      virus outbreak.
AB  - During follow-up of a 2012 US outbreak of lymphocytic choriomeningitis virus
      (LCMV), we conducted a trace-forward investigation. LCMV-infected feeder mice
      originating from a US rodent breeding facility had been distributed to >500
      locations in 21 states. All mice from the facility were euthanized, and no
      additional persons tested positive for LCMV infection. 

PMID- 24447900
TI  - Authors' reply to Vinden.

PMID- 24447899
TI  - Category fluency, latent semantic analysis and schizophrenia: a candidate gene
      approach.
AB  - BACKGROUND: Category fluency is a widely used task that relies on multiple
      neurocognitive processes and is a sensitive assay of cortical dysfunction,
      including in schizophrenia. The test requires naming of as many words belonging
      to a certain category (e.g., animals) as possible within a short period of time.
      The core metrics are the overall number of words produced and the number of
      errors, namely non-members generated for a target category. We combine a
      computational linguistic approach with a candidate gene approach to examine the
      genetic architecture of this traditional fluency measure. METHODS: In addition to
      the standard metric of overall word count, we applied a computational approach to
      semantics, Latent Semantic Analysis (LSA), to analyse the clustering pattern of
      the categories generated, as it likely reflects the search in memory for
      meanings. Also, since fluency performance probably also recruits verbal learning
      and recall processes, we included two standard measures of this cognitive
      process: the Wechsler Memory Scale and California Verbal Learning Test (CVLT). To
      explore the genetic architecture of traditional and LSA-derived fluency measures
      we employed a candidate gene approach focused on SNPs with known function that
      were available from a recent genome-wide association study (GWAS) of
      schizophrenia. The selected candidate genes were associated with language and
      speech, verbal learning and recall processes, and processing speed. A total of 39
      coding SNPs were included for analysis in 665 subjects. RESULTS AND DISCUSSION:
      Given the modest sample size, the results should be regarded as exploratory and
      preliminary. Nevertheless, the data clearly illustrate how extracting the meaning
      from participants' responses, by analysing the actual content of words, generates
      useful and neurocognitively viable metrics. We discuss three replicated SNPs in
      the genes ZNF804A, DISC1 and KIAA0319, as well as the potential for computational
      analyses of linguistic and textual data in other genomics tasks.

PMID- 24447901
TI  - Controlled dynamic stability as the next step in "biologic plate osteosynthesis" 
      a pilot prospective observational cohort study in 34 patients with distal tibia
      fractures.
AB  - INTRODUCTION: Delayed bone healing is an eminent problem in the operative
      treatment of distal tibia fractures. To address this problem from a biomechanical
      perspective, the DLS 3.7 (Dynamic Locking Screw 3.7 mm) as a new generation of
      locking screws has been developed. This screw enables the surgeon to control the
      rigidity of the plate osteosynthesis and thereby to expand clinical options in
      cases where the bridge plating is chosen for fracture treatment. PURPOSE: The
      purpose of the present prospective study was to evaluate the safety use of the
      DLS 3.7 in distal tibia fractures where bridge plating osteosynthesis is
      recommended. METHODS: In a prospective non-controlled cohort study, 34 patients
      with acute distal tibia fractures (AO 43 A-C) were treated with an angular stable
      plate fixation using DLS 3.7 or LHS 3.5. Follow-up examinations were performed
      three, six, twelve, and twenty-four weeks postoperatively and all registered
      complications were carefully collected. RESULTS: A total of 34 patients were
      prospectively enrolled in this study with a minimum follow-up of 6 months or
      obvious osseous consolidation at an earlier stage. No complications directly
      related to the DLS 3.7 were recorded and no infections were observed.
      CONCLUSIONS: This observational study could show that the DLS 3.7 in combination
      with locking compression plates provides a secure and easy application. According
      to the recent literature inter-fragmentary micro-motion is one evident goal to
      increase the reliability in fracture healing. The new DLS 3.7 with a maximum
      micro-motion of 0.2 mm combines the advantage of micro-motion with the well-known
      advantages of angular stable plate fixation.

PMID- 24447902
TI  - [General malaise in the elderly patient as a presentation of antisynthetase
      syndrome without muscle involvement].

PMID- 24447904
TI  - Introduction to the special issue 'viral membrane proteins - channels for
      cellular networking'.

PMID- 24447903
TI  - Frequency of immunoglobulin G4-related aortitis in cases with aortic resection
      and their clinical characteristics compared to other aortitises.
AB  - AIMS: To identify the frequency of immunoglobulin G4 (IgG4)-related aortitis in
      patients who undergo aorta surgery and are diagnosed by pathology as having
      chronic aortic inflammation and to compare IgG4-related aortitis with other non
      infectious aortitises in terms of clinical characteristics. METHODS: The aorta
      specimen pathological reports of 1418 patients who underwent aortic aneurysm or
      dissection surgery were reviewed. In total, 41 had chronic aortic inflammation
      without atherosclerosis, cancer or infection. Their aorta biopsy specimens were
      subjected to IgG4 immunostaining. IgG4-related aortitis was diagnosed if the IgG4
      positive plasma cell count exceeded 50 per high power field (HPF), the ratio of
      IgG4-positive to IgG-positive plasma cells exceeded 50% and dense
      lymphoplasmacytic infiltration, fibrosis and/or obliterative phlebitis were
      observed. RESULTS: Of the 41 non-infectious aortitis cases, 29, six and six had
      idiopathic aortitis, Takayasu's arteritis and Behcet's aortitis, respectively. Of
      the 29 idiopathic aortitis cases, three had IgG4-related aortitis. All were male
      and > 65 years of age. Two had thoracic aortic aneurysms and one had an abdominal
      aortic aneurysm. Their IgG4-positive plasma cell counts were 60/HPF or higher;
      lymphoplasmacytic infiltration and/or fibrosis, but not obliterative phlebitis,
      were observed. The IgG4-related aortitis cases were older (67 [range, 65-69]
      years) than the Takayasu's arteritis (47.5 [38-58] years) or Behcet's aortitis
      (47 [31-56] years) cases and more likely to be male than the Takayasu's arteritis
      cases (100% vs. 17%). CONCLUSION: In patients with chronic aortic inflammation,
      7% had IgG4-related aortitis. This disease may be more common in older male
      patients than in other demographic groups.

PMID- 24447905
TI  - Antibacterial effects of natural tenderizing enzymes on different strains of
      Escherichia coli O157:H7 and Listeria monocytogenes on beef.
AB  - This study determined the efficacy of actinidin and papain on reducing Listeria
      monocytogenes and three mixed strains of Escherichia coli O157:H7 populations on
      beef. The average reduction of E. coli O157:H7 was greater than that of L.
      monocytogenes and higher concentrations of either protease yielded greater
      reduction in bacterial populations. For instance, actinidin at 700 mg/ml
      significantly (p<=0.05) reduced the population of L. monocytogenes by 1.49 log
      cfu/ml meat rinse after 3h at 25 & 35  degrees C, and by 1.45 log cfu/ml rinse
      after 24h at 5  degrees C, while the same actinidin concentration significantly
      reduced the populations of three mixed strains of E. coli O157:H7 by 1.81 log
      cfu/ml rinse after 3h at 25 & 35  degrees C, and 1.94 log cfu/ml rinse after 24h
      at 5  degrees C. These findings suggest that, in addition to improving the
      sensory attributes of beef, proteolytic enzymes can enhance meat safety when
      stored at suitable temperatures.

PMID- 24447906
TI  - Dynamic stability margin using a marker based system and Tekscan: a comparison of
      four gait conditions.
AB  - Stability during gait is maintained through control of the center of mass (CoM)
      position and velocity in relation to the base of support (BoS). The dynamic
      stability margin, or the interaction of the extrapolated center of mass with the
      closest boundary of the BoS, can reveal possible control errors during gait. The
      purpose of this study was to investigate a marker based method for defining the
      BoS, and compare the dynamic stability margin throughout gait in comparison to a
      BoS defined from foot pressure sensors. The root mean squared difference between
      these two methodologies ranged from 0.9 cm to 3.5 cm, when walking under four
      conditions: plantigrade, equinus, everted, and inverted. As the stability margin
      approaches -35 cm prior to contralateral heel strike, there was approximately 90%
      agreement between the two systems at this time point. Underestimation of the
      marker based dynamic stability margin or overestimation of the pressure based
      dynamic stability margin was due to inaccuracies in defining the medial boundary
      of the BoS. Overall, care must be taken to ensure similar definitions of the BoS
      are utilized when comparing the dynamic stability margin between participants and
      gait conditions.

PMID- 24447907
TI  - Validation of National Institutes of Health global scoring system for chronic
      graft-versus-host disease (GVHD) according to overall and GVHD-specific survival.
AB  - A new severity grading system for graft-versus-host disease (GVHD) was
      established by the National Institutes of Health (NIH) consensus criteria (NCC).
      However, its prognostic value still needs to be validated. Four hundred twenty
      five consecutive patients who survived beyond 100 days after allogeneic stem cell
      transplantation were reviewed and reclassified using NCC. GVHD-specific survival
      (GSS) and cumulative incidence of relapse were compared according to the NIH
      global score at the onset and peak of chronic GVHD (cGVHD). Of 346 patients with
      cGVHD diagnosed by the Revised Seattle Criteria, 317 patients were reclassified
      according to the NCC as classic cGVHD (n = 144) and overlap syndrome (n = 173).
      The NIH global scores at onset were mild (43.2%), moderate (42.3%), and severe
      (14.5%), whereas more moderate (55.5%) and severe (31.6%) cGVHD was observed at
      the peak of cGVHD. With a median follow-up duration of 34 months, the 5-year GSS
      was significantly worse for the severe group than the moderate/mild groups at
      onset and at peak: 50.9% +/- 7.8% versus 89.7% +/- 3.2% versus 93.5% +/- 2.4% at
      onset (P < .001) and 69.1% +/- 5.2% versus 93.2% +/- 2.1% versus 97.3% +/- 2.7%
      at peak (P < .001). Severe NIH global score at onset and peak were confirmed as a
      poor prognostic factor for GSS in multivariate analysis. The cumulative incidence
      of relapse did not differ among the severity groups at onset or peak. In
      conclusion, the new NIH global scoring system was shown to differentiate a high
      risk group of patients (with severe grade cGVHD) in terms of long-term transplant
      outcomes.

PMID- 24447908
TI  - Critical review on the Environmental Risk Assessment of medicinal products for
      human use in the centralised procedure.
AB  - In this article we analyse the Environmental Risk Assessment (ERA) of 59
      medicinal products for human use authorised in the EU through the centralised
      procedure between 2011 and 2012, to establish whether company submissions are
      compliant with the European Medicines Agency (EMA) guideline and complete in
      terms of data and study reports provided. The most frequent questions raised by
      EU regulatory authorities are described, together with an evaluation of the
      presence and quality of ERA-related information in published regulatory
      assessment documents. The results of this review show recent improvement in ERA
      related data presented in regulatory assessment documents available to the public
      while also highlighting a need to develop further guidance on environmental
      issues in order to assist applicants improve their ERA dossiers and overcome
      current shortcomings. 

PMID- 24447909
TI  - Distribution of aliphatic hydrocarbons, polycyclic aromatic hydrocarbons and
      organochlorinated pollutants in deep-sea sediments of the Southern Cretan margin,
      Eastern Mediterranean Sea: a baseline assessment.
AB  - Deep sediments from the southern Cretan margin were analyzed to establish
      baseline levels for various types of organic pollutants before the anticipated
      intensification of anthropogenic activities. The total concentration of aliphatic
      hydrocarbons (SigmaAH:326-3758ngg(-1), dry weight) was similar to those reported
      for deep sediments of the western Mediterranean Sea, while considerably lower
      levels were measured for polycyclic aromatic hydrocarbons (SigmaPAH:9-60ngg(-1)).
      Source-diagnostic ratios suggested that the aliphatic hydrocarbons in sediments
      were mainly of terrestrial biogenic origin, while polycyclic aromatic
      hydrocarbons stemmed from the deposition of long-range transported combustion
      aerosols. Among the organochlorinated compounds analyzed, beta
      hexachlorocyclohexane (beta-HCH:222-7052pgg(-1)), 1,1,1-trichloro-2,2-bis(4
      chlorophenyl)ethane (p,p'-DDT:37-2236pgg(-1)) and polychlorinated biphenyls
      (SigmaPCB:38-1182pgg(-1)) showed the highest abundance in sediments. The presence
      of HCHs and PCBs was attributed to historical inputs that have undergone
      extensive weathering, whereas an ongoing fresh input was suggested for p,p'-DDT.
      Multiple linear regression analysis revealed that the levels of the various
      pollutants in sediments were controlled by different factors, but with organic
      carbon content playing a prominent role in most cases. 

PMID- 24447910
TI  - Subclinical synovitis detected by ultrasound in children affected by coeliac
      disease: a frequent manifestation improved by a gluten-free diet.
AB  - OBJECTIVES: Coeliac disease (CD) is a chronic autoimmune disease of the small
      intestine caused by the ingestion of gluten, in which musculoskeletal
      manifestations may occur. Aim of this study was to evaluate the prevalence and
      severity of joint involvement in paediatric patients with CD using
      musculoskeletal ultrasound (US). METHODS: Consecutive paediatric CD patients were
      enrolled and underwent US evaluations at level of knees, hips and ankles. The
      presence of joint effusion (JE), synovial hypertrophy, power Doppler signal and
      structural damage lesions (bone irregularities and erosions) was registered.
      Inflammatory abnormalities were scored on a semi-quantitative scale (0-3), and
      structural damage lesions on a dichotomous scale (0-1). RESULTS: Seventy-four CD
      children (mean age: 7.6 years; range: 1-14.2; M/F 24/50) were enrolled. Thirty
      eight were on a gluten-containing diet (GCD) and 36 on a gluten-free diet (GFD).
      US showed the presence of abnormalities in 23 patients overall (31.1%); JE was
      the most frequently observed change (23/23). US abnormalities were observed in 19
      patients (50.0%) of GCD group and in 4 of GFD group (11.1%, p=0.007).
      Interestingly, 12/23 (52.2%) patients with US-detected changes were asymptomatic.
      CONCLUSIONS: This is the first US study demonstrating joint involvement in
      children with CD. JE, the most frequent manifestation, was present also in
      asymptomatic patients and was reduced in those on GFD. These findings may
      indicate that, also at joint level, an inflammatory response represented by the
      appearance of JE may be induced by exposure to gluten.

PMID- 24447913
TI  - Health care satisfaction among foreign residents in Taiwan - An assessment and
      improvement.
AB  - BACKGROUND: In 2012, almost half-million foreigners (2.3% of the total
      population) from 160 countries were estimated to live in Taiwan. In 2010,
      approximately eighty-seven percent of the population expressed high satisfaction
      in the national health care system of Taiwan. However, satisfaction level among
      foreign residents towards the Taiwanese health care system has not been clearly
      documented in the literature.OBJECTIVE: In this study, we assessed satisfaction
      level among foreign residents for receiving healthcare facility in Taiwanese
      hospital. In addition, the study came out with some potential solutions to
      improve health care received by them. METHODS: Human-Centered Design (HCD)
      approach was deployed, which included three phases: observation, pattern
      recognition, and ideation and delivery. Each phase involved various steps.
      Techniques, such as ethnography, interview, discussion, and survey were used in
      accomplishing various steps within each phase. Four participants and two
      facilitators from Taiwan took part in the study. RESULTS: The study revealed
      various stories, insights, and themes about the health care received by the
      foreigners in Taiwan. In addition, some potential solutions and immediate
      available opportunities were recommended to improve their health care.
      CONCLUSIONS: The results provided a deeper understanding into the satisfaction
      level among foreign residents in Taiwan. For instance, this study pointed out the
      need to improve English proficiency of hospital's administrative staffs because a
      lack of English language proficiencies was found to be a major barrier in
      delivering quality health care to foreign residents. Therefore, adoption of
      various training modalities, such as English training using mobile device based
      games, role-play, and hospital's workflow depiction using English posters were
      recommended.

PMID- 24447912
TI  - Exploration of novel cellular and serological antigen biomarkers in the ORFeome
      of Mycobacterium tuberculosis.
AB  - Increasing evidence demonstrates that antigen-specific cellular and humoral
      immunity plays an indispensable role in protection against Mycobacterium
      tuberculosis infection. Antigen is a key element in the development of a
      successful diagnostic method and vaccine. However, few antigens are available,
      and a systemic study on M. tuberculosis ORFeome-based antigen screening is still
      lacking. In the current study, a genome-wide examination was conducted on high
      throughput M. tuberculosis encoding proteins and novel antigens were identified
      via a comprehensive investigation of serological and antigen-specific cellular
      responses. The serological immunoglobulin G level of each protein was detected in
      pooled sera from 200 pulmonary tuberculosis patients by means of semi
      quantitative Western blot. Of the 1,250 detected proteins, 29 were present at a
      higher level relative to the commercialized 38-kDa protein. Furthermore, the top
      12 of the 29 proteins had not been previously reported, and their antigenicity
      was validated in serum from each individual patient. Results confirmed that the
      12 proteins displayed nearly identical immunoglobulin G antibody levels in
      patients with pulmonary and extrapulmonary tuberculosis. Antigen-specific
      cellular interferon-gamma secretion was also evaluated using a cell-based ELISPOT
      assay. Thirty-four of the proteins were able to induce positive interferon-gamma
      production by peripheral blood mononuclear cells from pulmonary tuberculosis
      patients as judged by positive (commercial ESAT-6 antigen) and negative controls.
      The top 4 candidates out of the 34 proteins displayed good accuracy ranging from
      50% to 80% compared with the commercial ESAT-6 antigen. Subsequent epitope
      examination confirmed that a pool of peptides, including a 25aa peptide from
      Rv1198, demonstrated significant tuberculosis-specific cellular interferon-gamma
      production. Overall, the current study draws significant attention to novel M.
      tuberculosis antigens, many of which have not been previously reported. This
      discovery provides a large amount of useful information for the diagnosis of
      tuberculosis and the development of vaccines to provide protection against
      tuberculosis. 

PMID- 24447911
TI  - Docosahexaenoic acid reverses angiotensin II-induced RECK suppression and cardiac
      fibroblast migration.
AB  - The omega-3 polyunsaturated fatty acids (omega-3 fatty acids) eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) have been reported to inhibit or delay
      the progression of cardiovascular diseases, including myocardial fibrosis.
      Recently we reported that angiotensin II (Ang II) promotes cardiac fibroblast
      (CF) migration by suppressing the MMP regulator reversion-inducing-cysteine-rich
      protein with Kazal motifs (RECK), through a mechanism dependent on AT1, ERK, and
      Sp1. Here we investigated the role of miR-21 in Ang II-mediated RECK suppression,
      and determined whether the omega-3 fatty acids reverse these effects. Ang II
      induced miR-21 expression in primary mouse cardiac fibroblasts (CFs) via ERK
      dependent AP-1 and STAT3 activation, and while a miR-21 inhibitor reversed Ang II
      induced RECK suppression, a miR-21 mimic inhibited both RECK expression and Ang
      II-induced CF migration. Moreover, Ang II suppressed the pro-apoptotic PTEN, and
      the ERK negative regulator Sprouty homologue 1 (SPRY1), but induced the
      metalloendopeptidase MMP2, all in a manner that was miR-21-dependent. Further,
      forced expression of PTEN inhibited Akt phosphorylation, Sp1 activation, and MMP2
      induction. Notably, while both EPA and DHA reversed Ang II-mediated RECK
      suppression, DHA appeared to be more effective, and reversed Ang II-induced miR
      21 expression, RECK suppression, MMP2 induction, and CF migration. These results
      indicate that Ang II-induced CF migration is differentially regulated by miR-21
      mediated MMP induction and RECK suppression, and that DHA has the potential to
      upregulate RECK, and therefore may exert potential beneficial effects in cardiac
      fibrosis. 

PMID- 24447914
TI  - Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic
      acid.
AB  - Helicobacter pylori colonizes half of the world population and is associated with
      gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA),
      an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor
      effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless,
      the concentration of DHA shown to reduce H. pylori mice gastric colonization was
      ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we
      hypothesize that other mechanisms, in addition to DHA direct antibacterial
      effect, must be responsible for the reduction of the infection burden. In the
      present study we investigated if DHA affects also H. pylori growth, by reducing
      the availability of membrane cholesterol in the epithelial cell for H. pylori
      uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl
      glucosides in H. pylori were determined by thin layer chromatography and gas
      chromatography. The consequences of epithelial cells' cholesterol depletion on H.
      pylori growth were assessed in liquid cultures. We show that H. pylori uptakes
      cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in
      epithelial cells, decreases its de novo synthesis, leading to a lower synthesis
      of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to
      cholesterol influences the bacterium response to the direct inhibitory effect of
      DHA. Overall, our results suggest that a direct effect of DHA on H. pylori
      survival is modulated by its access to epithelial cell cholesterol, supporting
      the notion that cholesterol enhances the resistance of H. pylori. The cholesterol
      dependent resistance of H. pylori to antimicrobial compounds raises new important
      aspects for the development of new anti-bacterial strategies. 

PMID- 24447916
TI  - Synthesis, molecular structure, and spectroelectrochemistry of a nitrosyl iron
      porphyrin containing an unsymmetrical xanthene-linked porphyrin core.
AB  - Synthetic nitrosyl porphyrins with meso-aryl substituents are potential models
      for the biologically-important NO-bound P460 heme cofactor. A five-coordinate
      iron nitrosyl tetraaryl-porphyrin (HTPPX-CO2H)Fe(NO) containing a xanthene-based
      meso substituent has been prepared. The crystal structure of this formally
      {FeNO}7 complex reveals an ordered axial and bent NO ligand (?FeNO=142.5(6)A)
      displaying an off-axis tilt of the nitrosyl N atom from the heme normal by 9.2
      degrees . Surprisingly, the porphyrin core does not display the expected
      asymmetry in FeN(por) distances frequently observed in iron nitrosyl porphyrins.
      The redox behavior as determined by cyclic voltammetry reveals, in contrast to
      most (por)Fe(NO) compounds, a fast NO dissociation after electrooxidation in
      CH2Cl2 to result in a net chemically-irreversible oxidation at Epa=+0.77V vs
      Ag/AgCl. IR spectroelectrochemistry reveals a recombination, on the
      spectroelectrochemistry time-scale, of the dissociated NO on oxidation with
      electrogenerated [(HTPPX-CO2H)Fe]+.

PMID- 24447915
TI  - Phenol-soluble modulins.
AB  - PSMs are a recently discovered family of short, amphipathic, alpha-helical
      peptides in staphylococci. Several PSMs are key virulence determinants,
      particularly in highly virulent Staphylococcus aureus strains. PSMalpha peptides
      of S. aureus facilitate neutrophil lysis after phagocytosis, and are key
      contributors to several infection types, including skin infection and bacteremia.
      Furthermore, all PSMs contribute to biofilm structuring and the dissemination of
      biofilm-associated infection. Cytolytic PSMs as produced by S. aureus appear to
      have evolved from original functions in the non-infectious lifestyle of
      staphylococci. The surfactant properties of PSMs, which they all share, are
      believed to facilitate growth on epithelial surfaces. The basic role of PSMs in
      staphylococcal physiology is underscored, for example, by their exceptionally
      strict and direct control by quorum-sensing and the presence of a dedicated
      secretion system. Targeting PSMs for anti-staphylococcal drug development may be
      a promising approach to overcome the problems associated with widespread
      antibiotic resistance in staphylococci. 

PMID- 24447917
TI  - The convergence of endosomal and autophagosomal pathways: implications for APP
      CTF degradation.
AB  - We have reported previously that autophagy is responsible for amyloid precursor
      protein-C-terminal fragment (APP-CTF) degradation and therefore Abeta clearance.
      To elucidate the underlying mechanism, using LC3 affinity purification and mass
      spectrometry analysis, immunoprecipitation (IP), as well as live imaging
      analysis, we identified and demonstrated that the adaptor-related protein complex
      2 (AP2) and PICALM (phosphatidylinositol binding clathrin assembly protein) are
      in a complex with LC3 and APP-CTF. Taken together, this new set of data suggests
      that the AP2-PICALM complex functions as an autophagic cargo receptor for the
      recognition and shipment of APP-CTF from the endocytic pathway to the LC3
      dependent autophagic degradation pathway. Interestingly this AP2-LC3 connection
      seems to be involved in chemically-induced APP-CTF clearance as we observed using
      the small compound SMER28. The effect observed following SMER28 was significantly
      reduced after silencing AP2. While more work is required to elucidate the
      detailed molecular mechanisms involved, our actual data suggest that there is
      some level of specificity in the steps mentioned above. 

PMID- 24447918
TI  - [Venous catheter-related infections].
AB  - Venous catheter-related infections are a problem of particular importance, due to
      their frequency, morbidity and mortality, and because they are potentially
      preventable clinical processes. At present, the majority of hospitalized patients
      and a considerable number of outpatients are carriers of these devices. There has
      been a remarkable growth of knowledge of the epidemiology of these infections,
      the most appropriate methodology for diagnosis, the therapeutic and, in
      particular, the preventive strategies. Multimodal strategies, including
      educational programs directed at staff and a bundle of simple measures for
      implementation, applied to high-risk patients have demonstrated great
      effectiveness for their prevention. In this review the epidemiology, the
      diagnosis, and the therapeutic and preventive aspects of these infections are
      updated. 

PMID- 24447919
TI  - [Epidemiology of hepatitis E virus infection in Spain].
AB  - The general features of the epidemiology and ecology of hepatitis E virus in
      Spain are already known after 20 years of investigations. Genotype 3 strains,
      mainly from sub-genotype 3f, circulated among swine livestock and certain wild
      mammals, and would be sporadically transmitted to humans through direct contact
      with the reservoirs or by consumption of foods derived from them. Bivalve
      shellfish contaminated by hepatitis E virus from sewage could also play a role in
      transmission. Although the interpretation of results from seroprevalence studies
      in low endemic settings is still controversial, antibody to hepatitis E virus
      displays an overall prevalence less than 10% among the population of Spain,
      increasing significantly with age. From the, approximately, 150 cases of acute
      hepatitis E recorded in the international literature, males older than 40 years,
      suffering a mild, locally acquired disease predominate. In addition, hepatitis E
      might be more frequent in the North of the country than in other regions.
      Although the disease does not usually have a great clinical relevance, the
      occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant,
      chronic hepatitis E virus infections among the immunocompromised would recommend
      the surveillance of the infection by the public health authority and a better
      implementation of specific diagnostic procedures in clinical laboratories. 

PMID- 24447920
TI  - Right knee pain, swelling and fever in a young immunocompetent male.

PMID- 24447921
TI  - [Nosocomial infections in long-term health care facilities].
AB  - The long-term care facilities (LTCF) are the health care level that integrates
      medical assistance and social services according to the requirements of its
      beneficiaries. There is a great variability depending on the users profile, the
      professional staff and accessibility to technical resources for diagnosis,
      treatment or rehabilitation. In LTCF different factors are shaping a challenge in
      the infection control. These factors are high prevalence of infection and
      colonization by multiresistant microorganisms (MROs), a high rate of, often
      inadequate, antibiotic prescriptions, the high transfer of hospital patients, and
      the lack of diagnostic resources. In infection studies in LTCF, one of the main
      problems is the lack of standard, and well defined, infection criteria. The
      special features of infections in the elderly population, together with the
      limited resources, make it necessary to establish standard and worldwide
      validated criteria in order achieve appropriate monitoring and control of
      infection. The most common infection is the respiratory, followed by the urinary,
      skin and soft tissue, gastro-intestinal tract, and eyes. The problematic
      microorganisms most frequently identified in LTCF are enterobacteriaceae extended
      spectrum beta lactamase, Pseudomonas aeruginosa and methicillin-resistant
      Staphylococcus aureus (MRSA). A successful infection control mainly depends on
      two actions. First, a high compliance of standard precautions and second, patient
      organization according to the risk of transmission of a particular MROs
      infection, especially MRSA. This risk classification may be a way to rationalize
      application measures, and the incorporation of ethical and legal issues. The
      level of stratification is established mainly according to the condition of being
      colonized or infected, the MROs anatomical location, and the degree of behavioral
      disorders suffered by the patient. Implementation of extensive screening programs
      or complex monitoring programs, as in acute care hospitals are not indicated. The
      epidemiological surveillance must adapt to clinical guidelines, with the
      registering of colonized and infected patients being mandatory, along with the
      coordination between health and social systems by applying global control
      programs.

PMID- 24447922
TI  - [Hospitalization due to whooping cough in Spain (1997-2011)].
AB  - INTRODUCTION: Pertussis incidence has increased in recent years in countries with
      high vaccination coverage. The aim of this study was to determine the health
      impact of pertussis in Spain in the period 1997-2011 in relation to
      hospitalizations, mortality, and associated costs. METHODS: We retrospectively
      analyzed hospital discharges included in the Minimum Data Set (MDS) in Spain for
      the period 1997-2011, with a primary or secondary diagnosis related to pertussis.
      We calculated incidence rates of hospitalization for pertussis (per 100,000) per
      year, by age group and by Autonomous Region, along with the mortality and
      lethality rates. RESULTS: A total of 8,331 hospital discharges with a diagnosis
      of pertussis were recorded in Spain between 1997 and 2011. The overall incidence
      of pertussis hospitalizations was 1.3 cases per 100,000 inhabitants. The large
      majority (92%) of hospitalizations occurred in children under one year of age,
      with an incidence of 115.2 hospitalizations per 100,000. There were 47 deaths, 37
      (79%) in the group of children under 1 year and 6 (13%) in the group older than
      65 years. The estimated cost of hospitalization for pertussis was 1,841 euros.
      CONCLUSION: The epidemiology of severe cases of pertussis, and its clinical and
      economic impact, confirms the need to modify the vaccination strategies for Spain
      to achieve more effective control in the most vulnerable groups.

PMID- 24447923
TI  - Purification of an inducible DNase from a thermophilic fungus.
AB  - The ability to induce an extracellular DNase from a novel thermophilic fungus was
      studied and the DNAse purified using both traditional and innovative purification
      techniques. The isolate produced sterile hyphae under all attempted growing
      conditions, with an average diameter of 2 um and was found to have an optimal
      temperature of 45  degrees C and a maximum of 65  degrees C. Sequencing of the
      internal transcribed region resulted in a 91% match with Chaetomium sp.,
      suggesting a new species, but further clarification on this point is needed. The
      optimal temperature for DNase production was found to be 55  degrees C and was
      induced by the presence of DNA and/or deoxyribose. Static growth of the organism
      resulted in significantly higher DNase production than agitated growth. The DNase
      was purified 145-fold using a novel affinity membrane purification system with
      25% of the initial enzyme activity remaining. Electrophoresis of the purified
      enzyme resulted in a single protein band, indicating DNase homogeneity. 

PMID- 24447925
TI  - Development of molecularly imprinted polymer in porous film format for binding of
      phenol and alkylphenols from water.
AB  - Molecularly imprinted polymers (MIPs) were fabricated on glass slides with a
      "sandwich" technique giving ~20 um thick films. Methanol/water as a solvent, and
      polyethyleneglycol and polyvinylacetate as solvent modifiers, were used to give a
      porous morphology, which was studied with scanning electron microscopy and
      gravimetric analysis. Various MIPs were synthesized through non-covalent
      imprinting with phenol as the template; itaconic acid, 4-vinylpyridine, and
      styrene as monomers; ethylene glycol dimethacrylate, triethylene glycol
      dimethacrylate, and pentaerythritol triacrylate (PETA) as cross-linkers. Binding
      and imprinting properties of the MIPs were evaluated based on phenol adsorption
      isotherms. Since phenol has only one weakly acidic hydroxyl group and lacks
      unique structural characteristics necessary for binding specificity, the
      preparation of selective MIPs was challenging. The recognition of phenol via
      hydrogen bonding is suppressed in water, while hydrophobic interactions, though
      promoted, are not specific enough for highly-selective phenol recognition.
      Nevertheless, the styrene-PETA MIP gave modest imprinting effects, which were
      higher at lower concentrations (Imprinting Factor (IF) = 1.16 at 0.5 mg.L(-1)).
      The isotherm was of a Freundlich type over 0.1-40 mg.L(-1) and there was broad
      cross-reactivity towards other structurally similar phenols. This shows that
      phenol MIPs or simple adsorbents can be developed based on styrene for
      hydrophobic binding, and PETA to form a tighter, hydrophilic network.

PMID- 24447924
TI  - Molecular basis of cardiac myxomas.
AB  - Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer.
      Metastatic cardiac tumors are about 100 times more common than the primary
      tumors. About 90% of primary cardiac tumors are benign, and of these the most
      common are cardiac myxomas. Approximately 12% of primary cardiac tumors are
      completely asymptomatic while others present with one or more signs and symptoms
      of the classical triad of hemodynamic changes due to intracardiac obstruction,
      embolism and nonspecific constitutional symptoms. Echocardiography is highly
      sensitive and specific in detecting cardiac tumors. Other helpful investigations
      are chest X-rays, magnetic resonance imaging and computerized tomography scan.
      Surgical excision is the treatment of choice for primary cardiac tumors and is
      usually associated with a good prognosis. This review article will focus on the
      general features of benign cardiac tumors with an emphasis on cardiac myxomas and
      their molecular basis. 

PMID- 24447926
TI  - In silico discovery of aminoacyl-tRNA synthetase inhibitors.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of
      amino acids to their cognate tRNA. They play a pivotal role in protein synthesis
      and are essential for cell growth and survival. The aaRSs are one of the leading
      targets for development of antibiotic agents. In this review, we mainly focused
      on aaRS inhibitor discovery and development using in silico methods including
      virtual screening and structure-based drug design. These computational methods
      are relatively fast and cheap, and are proving to be of great benefit for the
      rational development of more potent aaRS inhibitors and other pharmaceutical
      agents that may usher in a much needed generation of new antibiotics. 

PMID- 24447928
TI  - Extracellular disposal of tumor-suppressor miRs-145 and -34a via microvesicles
      and 5-FU resistance of human colon cancer cells.
AB  - The dysregulation of microRNA (miRNA) expression causes various kinds of
      diseases. Especially, alterations in miRNA expression levels are frequently
      observed in human tumor cells and are associated with cancer pathogenesis.
      Earlier we established Fluorouracil (5-FU)-resistant human colon cancer DLD-1
      cells (DLD-1/5FU) from parental 5-FU- sensitive DLD-1 cells. In the present
      study, we examined the expression of miRNA in each cell line and in its
      extracellular microvesicles (MVs) before and after treatment with 5-FU. The
      nascent RNAs of anti-oncogenic miR-34a and -145 labeled with EU in both cells
      were proved to be transferred into MVs in both cell lines. The levels of miR-34a
      and -145 in the cells and in their MVs were not largely different in the two cell
      lines, and a substantial amount of both miRNAs was secreted by both cell lines
      even in the steady-state condition. The exposure of both cell lines to 5-FU
      significantly increased the intracellular levels of miR-145 and miR-34a in the 5
      FU-sensitive DLD-1 cells, whereas the level of neither miR was elevated in the
      DLD-1/5FU cells. Interestingly, the amount of miR-145 detected in the small MVs
      shed into the medium of the parental cells was reduced after the treatment with 5
      FU. On the other hand, the intracellular expression of miR-34a in the DLD-1/5FU
      cells was down-regulated compared with that in the parental DLD-1 cells even in
      the steady-state condition. As to the miR-34a secreted into MVs, the increase in
      the level in DLD-1/5FU cells was greater than that in the parental DLD-1 cells
      after the treatment with 5-FU. Thus, the intra- and extracellular miR-145 and 
      34a were closely associated with 5-FU resistance, and the resistance was in part
      due to the enhanced secretion of miR-145 and -34a via MVs, resulting in low
      intracellular levels of both miRNAs. 

PMID- 24447927
TI  - Beyond the role of dietary protein and amino acids in the prevention of diet
      induced obesity.
AB  - High-protein diets have been shown to prevent the development of diet-induced
      obesity and can improve associated metabolic disorders in mice. Dietary leucine
      supplementation can partially mimic this effect. However, the molecular
      mechanisms triggering these preventive effects remain to be satisfactorily
      explained. Here we review studies showing a connection between high protein or
      total amino nitrogen intake and obligatory water intake. High amino nitrogen
      intake may possibly lower lipid storage, and prevent insulin resistance.
      Suggestions are made for further systematical studies to explore the relationship
      between water consumption, satiety, and energy expenditure. Moreover, these
      examinations should better distinguish between leucine-specific and unspecific
      effects. Research in this field can provide important information to justify
      dietary recommendations and strategies in promoting long-term weight loss and may
      help to reduce health problems associated with the comorbidities of obesity. 

PMID- 24447929
TI  - Phenoxybenzamine is neuroprotective in a rat model of severe traumatic brain
      injury.
AB  - Phenoxybenzamine (PBZ) is an FDA approved alpha-1 adrenergic receptor antagonist
      that is currently used to treat symptoms of pheochromocytoma. However, it has not
      been studied as a neuroprotective agent for traumatic brain injury (TBI). While
      screening neuroprotective candidates, we found that phenoxybenzamine reduced
      neuronal death in rat hippocampal slice cultures following exposure to oxygen
      glucose deprivation (OGD). Using this system, we found that phenoxybenzamine
      reduced neuronal death over a broad dose range (0.1 uM-1 mM) and provided
      efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine
      in the rat lateral fluid percussion model of TBI. When administered 8 h after
      TBI, phenoxybenzamine improved neurological severity scoring and foot fault
      assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also
      showed a significant improvement in both learning and memory compared to saline
      treated controls. We further examined gene expression changes within the cortex
      following TBI. At 32 h post-TBI phenoxybenzamine treated animals had
      significantly lower expression of pro-inflammatory signaling proteins CCL2,
      IL1beta, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective
      effect by reducing neuroinflammation after TBI. These data suggest that
      phenonxybenzamine may have application in the treatment of TBI. 

PMID- 24447931
TI  - Activity standardization of 134Cs and 137Cs.
AB  - The paper presents the results from a primary standardization of (137)Cs using
      two independent methods - efficiency tracing using PC-NaI coincidence and the
      TDCR method. The nuclides (60)Co and (134)Cs were used as the tracers. Primary
      standardization of the (134)Cs is also discussed. The efficiency extrapolation
      was carried out by measuring samples of varying mass and using the wet
      extrapolation method. The results obtained are in good agreement; the differences
      did not exceed 0.5%. The advantages, pitfalls and also possibilities for
      improvement of the procedures are discussed. 

PMID- 24447930
TI  - Circulating microRNAs as biomarkers of acute stroke.
AB  - MicroRNAs have been identified as key regulators of gene expression and thus
      their potential in disease diagnostics, prognosis and therapy is being actively
      pursued. Deregulation of microRNAs in cerebral pathogenesis has been reported to
      a limited extent in both animal models and human. Due to the complexity of the
      pathology, identifying stroke specific microRNAs has been a challenge. This study
      shows that microRNA profiles reflect not only the temporal progression of stroke
      but also the specific etiologies. A panel of 32 microRNAs, which could
      differentiate stroke etiologies during acute phase was identified and verified
      using a customized TaqMan Low Density Array (TLDA). Furthermore we also found 5
      microRNAs, miR-125b-2*, -27a*, -422a, -488 and -627 to be consistently altered in
      acute stroke irrespective of age or severity or confounding metabolic
      complications. Differential expression of these 5 microRNAs was also observed in
      rat stroke models. Hence, their specificity to the stroke pathology emphasizes
      the possibility of developing these microRNAs into accurate and useful tools for
      diagnosis of stroke. 

PMID- 24447932
TI  - Comparison of 90Y and 177Lu measurement capability in UK and European hospitals.
AB  - Comparison exercises involving (90)Y and (177)Lu were performed during 2009 and
      2012, respectively, to assess the measurement capability of hospitals in the UK
      and Europe. The results from the measurement of a typical liquid solution of
      (90)Y show that only 40% of participants could measure the solution to within 5%
      of the certificated value and that a significant -6% bias was present due to the
      use of non-standard geometries for the calibration of equipment. The results from
      the measurement of a standard liquid solution of (177)Lu show that 81% of
      participants could measure to within 5% of the certificated value and in fact 65%
      of these results were within 2% of the certificated value, showing administered
      activities can be far more accurately measured for (177)Lu than for (90)Y and
      that (177)Lu has a far smaller geometry dependence. These studies were performed
      to identify specific measurement issues in the user community and to identify
      areas where future research should be focused. In addition to this the work
      allows the participants to adjust measurement practice and identify key
      measurement issues. 

PMID- 24447933
TI  - Drug delivery system design and development for boron neutron capture therapy on
      cancer treatment.
AB  - We have already synthesized a boron-containing polymeric micellar drug delivery
      system for boron neutron capture therapy (BNCT). The synthesized diblock
      copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of
      biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte
      poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester
      (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz
      micelle has great potential to be boron drug delivery system with preliminary
      evaluation of biocompatibility and boron content. 

PMID- 24447934
TI  - Design, construction and application of a neutron shield for the treatment of
      diffuse lung metastases in rats using BNCT.
AB  - A model of multiple lung metastases in BDIX rats is under study at CNEA
      (Argentina) to evaluate the feasibility of BNCT for multiple, non-surgically
      resectable lung metastases. A practical shielding device that comfortably houses
      a rat, allowing delivery of a therapeutic, uniform dose in lungs while protecting
      the body from the neutron beam is presented. Based on the final design obtained
      by numerical simulations, the shield was constructed, experimentally
      characterized and recently used in the first in vivo experiment at RA-3. 

PMID- 24447935
TI  - Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT
      mediated thymidine phosphorylase expression in human non-small-cell lung cancer
      cells.
AB  - Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist
      used worldwide as an adjuvant hormone therapeutic agent in the treatment of
      breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity
      in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine
      phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is
      upregulated in cancers. In this study, tamoxifen treatment inhibited cell
      survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased
      TP mRNA and protein levels through AKT inactivation. Furthermore, expression of
      constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP
      protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast,
      combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen
      further decreased the TP expression and cell viability of NSCLC cells. Knocking
      down TP expression by transfection with small interfering RNA of TP enhanced the
      cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI
      774), an orally available small molecular inhibitor of epidermal growth factor
      receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC.
      Compared to a single agent alone, tamoxifen combined with erlotinib resulted in
      cytotoxicity and cell growth inhibition synergistically in NSCLC cells,
      accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and
      reduced TP protein levels. These findings may have implications for the rational
      design of future drug regimens incorporating tamoxifen and erlotinib for the
      treatment of NSCLC. 

PMID- 24447936
TI  - The complexities of the pathology-pathogenesis relationship in Alzheimer disease.
AB  - Current pathogenic theories for Alzheimer disease (AD) and aging favor the notion
      that lesions and their constituent proteins are the initiators of disease due to
      toxicity. Whether this is because structural pathology is traditionally viewed as
      deleterious, and whether this, in turn, is a fundamental misinterpretation of the
      relationship between pathology and pathogenesis across the spectrum of chronic
      diseases, remains to be determined. As more and more detailed information about
      the biochemical constituents of AD lesions becomes available, it may also be
      argued that just as much knowledge of cellular physiology as pathophysiology has
      been gained. Indeed, essentially all major proteins in AD lesions are derived
      from molecular cascades, which are in turn highly conserved across cells,
      tissues, and species. Moreover, the lesions themselves are observed in the
      cognitively intact, and sometimes in large numbers, while major consensus
      criteria indicate that an extent of pathology is normal with advanced age. As the
      medical science community continues to pursue lesion targeting for therapeutic
      purposes, the notion that AD pathology is indicative of an active host response
      or environmental adaptation, and therefore a poor target, is becoming clearer. 

PMID- 24447937
TI  - Secondary bone surgery should be necessary with soft-tissue surgery in
      developmental dysplasia of the hip after the age of 18 months.

PMID- 24447938
TI  - Response to letter to the editor: Comparison of soft tissue and bone surgeries in
      the treatment of developmental dysplasia of the hip in 18-24-month-old patients.

PMID- 24447939
TI  - Hip dislocation in Down syndrome.

PMID- 24447940
TI  - Outcome of traumatic hip dislocation in children.

PMID- 24447941
TI  - Characteristics of low-speed vehicle run-over events in children: an 11-year
      review.
AB  - OBJECTIVES: The purpose of this study was to investigate the characteristics
      associated with fatal and non-fatal low-speed vehicle run-over (LSVRO) events in
      relation to person, incident and injury characteristics, in order to identify
      appropriate points for intervention and injury prevention. METHODS: Data on all
      known LSVRO events in Queensland, Australia, over 11 calendar years (1999-2009)
      were extracted from five different databases representing the continuum of care
      (prehospital to fatality) and manually linked. Descriptive and multivariate
      analyses were used to analyse the sample characteristics in relation to
      demographics, health service usage, outcomes, incident characteristics, and
      injury characteristics. RESULTS: Of the 1641 LSVRO incidents, 98.4% (n=1615) were
      non-fatal, and 1.6% were fatal (n=26). Over half the children required admission
      to hospital (56%, n=921); mean length of stay was 3.4 days. Younger children aged
      0-4 years were more frequently injured, and experienced more serious injuries
      with worse outcomes. Patterns of injury (injury type and severity), injury
      characteristics (eg, time of injury, vehicle type, driver of vehicle, incident
      location), and demographic characteristics (such as socioeconomic status,
      indigenous status, remoteness), varied according to age group. Almost half
      (45.6%; n=737) the events occurred outside major cities, and approximately 10% of
      events involved indigenous children. Parents were most commonly the vehicle
      drivers in fatal incidents. While larger vehicles such as four-wheel drives (4WD)
      were most frequently involved in LSVRO events resulting in fatalities, cars were
      most frequently involved in non-fatal events. CONCLUSIONS: This is the first
      study, to the authors' knowledge, to analyse the characteristics of fatal and non
      fatal LSVRO events in children aged 0-15 years on a state-wide basis.
      Characteristics of LSVRO events varied with age, thus age-specific interventions
      are required. Children living outside major cities, and indigenous children, were
      over-represented in these data. Further research is required to identify the
      burden of injury in these groups.

PMID- 24447942
TI  - Characterisation of bovine viral diarrhoea virus (BVDV) isolates from an outbreak
      with haemorrhagic enteritis and severe pneumonia.
AB  - During 2007 a disease outbreak occurred in cattle in the Marmara region of
      western Turkey characterised by severe pneumonia and haemorrhagic enteritis in
      calves. Cases from three farms at different locations were examined and bovine
      viral diarrhoea virus (BVDV) isolated in all cases. Phylogenetic characterisation
      of the virus isolates allocated them in a new cluster tentatively named as BVDV
      1r. 

PMID- 24447943
TI  - Activation of Th17 cells in drug naive, first episode schizophrenia.
AB  - OBJECTIVE: The present study was to examine the role of pro-inflammatory T helper
      17 (Th17) cells in drug naive, first episode schizophrenia. METHOD: Patients with
      normal weight, drug naive, first episode schizophrenia and healthy controls were
      enrolled in the study. Flow cytometric analysis was performed to analyze the
      proportion of Th17 cells among the CD4(+) T cells. Plasma levels of interleukin
      17 (IL-17), interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) were examined
      using enzyme-linked immunosorbent assay (ELISA). Psychopathology was assessed
      using the Positive and Negative Syndrome Scale (PANSS). All measures were
      repeated for the patient group after 4 weeks of risperidone treatment. RESULTS:
      Sixty-nine patients with normal weight, drug naive, first episode schizophrenia
      and 60 healthy controls were enrolled. At baseline, the patient group hadz
      significantly higher proportions of Th17 cells and plasma levels of IFN-gamma and
      IL-6 compared with the control group (p's<0.01). Within the patient group, there
      were significant positive relationships between the proportion of Th17 cells,
      plasma levels of IL-17, IFN-gamma, IL-6 and the PANSS total score after
      controlling for potential confounding variables (p's<0.05). After 4weeks of
      risperidone treatment, the proportion of Th17 cells decreased significantly (p
      <0.001), and there was a significant positive relationship between the PANSS
      total score change rate and the change in proportion of Th17 cells (p = 0.039).
      CONCLUSIONS: Patients with normal weight, drug naive, first episode schizophrenia
      present activation of Th17 cells, which might be associated with therapeutic
      response after risperidone treatment.

PMID- 24447944
TI  - Functional connectivity of resting state EEG and symptom severity in patients
      with post-traumatic stress disorder.
AB  - OBJECTIVES: Post-traumatic stress disorder (PTSD) is thought to be a brain
      network disorder. This study aimed to examine the resting-state functional
      connectivity (FC) in patients with PTSD. METHODS: Thirty-three PTSD patients and
      30 age- and gender-matched healthy controls were recruited. Symptom severity of
      the PTSD patients was assessed, and 62-channel EEG was measured. EEGs were
      recorded during the resting state, with the eyes closed. Three nodal network
      measures to assess nodal centrality [nodal degree (Dnodal; connection strength),
      nodal efficiency (Enodal; communication efficiency), and betweenness centrality
      (BC; connection centrality)] were calculated in the delta, theta, alpha, beta,
      and gamma bands. RESULTS: Dnodal and Enodal of the beta and gamma bands were
      decreased in PTSD patients compared to healthy controls. These decreased nodal
      centrality values were observed primarily at the frontocentral electrodes. In
      addition, Dnodal of the beta and gamma bands was significantly correlated with
      depressive symptoms and increased arousal symptoms, respectively. Enodal of the
      beta and gamma bands was significantly correlated with re-experience, increased
      arousal, and the severity and frequency of general PTSD symptoms. CONCLUSION:
      Compared to controls, patients with PTSD were found to have decreased resting
      state FC, and these FC measures were significantly correlated with PTSD symptom
      severity. Our results suggest that resting-state FC could be a useful biomarker
      for PTSD.

PMID- 24447946
TI  - A hypothesis-driven pathway analysis reveals myelin-related pathways that
      contribute to the risk of schizophrenia and bipolar disorder.
AB  - Schizophrenia (SZ) and bipolar disorder (BD) are both severe neuropsychiatric
      disorders with a strong and potential overlapping genetic background. Multiple
      lines of evidence, including genetic studies, gene expression studies and
      neuroimaging studies, have suggested that both disorders are closely related to
      myelin and oligodendrocyte dysfunctions. In the current study, we hypothesized
      that the holistic effect of the myelin-related pathway contributes to the genetic
      susceptibility to both SZ and BD. We extracted pathway data from the canonical
      pathway database, Gene Ontology (GO), and selected a 'compiled' pathway based on
      previous literature. We then performed hypothesis-driven pathway analysis on GWAS
      data from the Psychiatric Genomics Consortium (PGC). As a result, we identified
      three myelin-related pathways with a joint effect significantly associated with
      both disorders: 'Myelin sheath' pathway (P(SZ) = 2.45E-7, P(BD) = 1.22E-3),
      'Myelination' pathway (P(SZ) = 2.10E-4, P(BD) = 2.53E-24), and 'Compiled' pathway
      (P(SZ) = 4.57E-8, P(BD) = 2.61E-9). In comparing the SNPs and genes in these
      three pathways across the two diseases, we identified a substantial overlap in
      nominally associated SNPs and genes, which could be susceptibility SNPs and genes
      for both disorders. From these observations, we propose that myelin-related
      pathways may be involved in the etiologies of both SZ and BD.

PMID- 24447945
TI  - Association between DAOA gene polymorphisms and the risk of schizophrenia,
      bipolar disorder and depressive disorder.
AB  - OBJECTIVE: Schizophrenia (SCZ), bipolar disorder (BD) and depressive disorder
      (DD) are common psychiatric disorders, which show common genetic vulnerability.
      Previous gene-disease association studies have reported correlations between d
      amino acid oxidase activator (DAOA) gene polymorphisms and the three psychiatric
      disorders. However, the findings were contradictory. A meta-analysis was
      therefore conducted to provide more robust investigations into DAOA polymorphisms
      and the risk of SCZ, BD and DD. METHODS: This meta-analysis recruited 46
      published studies up to July 2013, including 17,515 cases and 25,189 controls.
      Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the
      association between three specific DAOA SNPs and SCZ, BD and DD. Publication bias
      was tested by Begg's test and funnel plot, and heterogeneity was assessed by the
      Cochran's chi-square-based Q statistic and the inconsistency index (I(2)).
      Moreover, the robustness of the findings was estimated by cumulative meta
      analysis. RESULTS: DAOA genetic polymorphisms (M15, M18 and M23) were not found
      to confer a statistically significant increased risk of SCZ, BD or DD in the
      overall sample, or in Caucasians and Asians following subgroup analysis.
      CONCLUSION: The current study indicated that M15, M18 and M23 might not be the
      risk factor for SCZ, BD or DD. However, further studies are required to provide
      robust evidence to estimate the association between DAOA polymorphisms and
      psychiatric disorders.

PMID- 24447947
TI  - A novel approach to safe redo-sternotomy in a patient with aortocutaneous fistula
      from an infected ascending aorta graft.
AB  - This case describes a novel approach to a safe redo-sternotomy in a patient
      presenting with an aortocutaneous fistula from a previous infected ascending
      aorta graft.

PMID- 24447948
TI  - Clinical experience with Affinity Pixie oxygenation system in paediatric and
      infant patients.
AB  - INTRODUCTION: Great Ormond Street Children's Hospital undertakes over 500 open
      heart cardiothoracic procedures requiring cardiopulmonary bypass per year. Data
      from our centre show that many of our neonatal/paediatric patients require higher
      cardiac indexes than previously thought. We evaluated the new Pixie oxygenation
      system, rated from 0.1 L/min to 2 L/min, to determine if it could be used for
      these patients. METHODS: Between 2010 and 2012, 250 Pixie oxygenators were used
      on consecutive patients requiring correction of congenital cardiac defects. Data
      were collected on FiO2 requirements, oxygenator pressure drop and gaseous
      microemboli handling. Retrospective analysis was also undertaken on the
      procedures and demographics of all patients during 2011-2012 to determine the
      percentage of patients on whom the Pixie could be used. RESULTS: Analysis of the
      procedures undertaken at Great Ormond Street Hospital (GOSH) showed that 89% were
      in patients under 20 kg, requiring a flow rate of <2 L/min (at a base cardiac
      index of 2.8 L/min/m2). The maximum FiO2 required at 2.5 L/min was 85%. Gaseous
      microemboli were reduced by 82.5+/-9.9% and bubble volume was decreased by 94.3+/
      8.4% from the 'venous' pre-oxygenator to the 'arterial' post-oxygenator.
      DISCUSSION: The Pixie oxygenator proved effective at flows up to 2.5 L/min, with
      air-handling capabilities comparable with other oxygenators. This represents a
      single oxygenator that could potentially be used to cover 89% of our surgical
      procedures. However, we believe that, for the smallest patients (i.e., < 2 kg), a
      smaller priming oxygenator should be used in order to limit unnecessary
      haemodilution in this vulnerable group.

PMID- 24447949
TI  - Editorial announcement.

PMID- 24447950
TI  - Interplay between viral Tat protein and c-Jun transcription factor in controlling
      LTR promoter activity in different human immunodeficiency virus type I subtypes.
AB  - HIV-1 transcription depends on cellular transcription factors that bind to
      sequences in the long-terminal repeat (LTR) promoter. Each HIV-1 subtype has a
      specific LTR promoter configuration, and minor sequence changes in transcription
      factor binding sites (TFBSs) or their arrangement can influence transcriptional
      activity, virus replication and latency properties. Previously, we investigated
      the proviral latency properties of different HIV-1 subtypes in the SupT1 T cell
      line. Here, subtype-specific latency and replication properties were studied in
      primary PHA-activated T lymphocytes. No major differences in latency and
      replication capacity were measured among the HIV-1 subtypes. Subtype B and AE
      LTRs were studied in more detail with regard to a putative AP-1 binding site
      using luciferase reporter constructs. c-Jun, a member of the AP-1 transcription
      factor family, can activate both subtype B and AE LTRs, but the latter showed a
      stronger response, reflecting a closer match with the consensus AP-1 binding
      site. c-Jun overexpression enhanced Tat-mediated transcription of the viral LTR,
      but in the absence of Tat inhibited basal promoter activity. Thus, c-Jun can
      exert a positive or negative effect via the AP-1 binding site in the HIV-1 LTR
      promoter, depending on the presence or absence of Tat. 

PMID- 24447951
TI  - Absolute perfusion measurements and associated iodinated contrast agent time
      course in brain metastasis: a study for contrast-enhanced radiotherapy.
AB  - Contrast-enhanced radiotherapy is an innovative treatment that combines the
      selective accumulation of heavy elements in tumors with stereotactic irradiations
      using medium energy X-rays. The radiation dose enhancement depends on the
      absolute amount of iodine reached in the tumor and its time course. Quantitative,
      postinfusion iodine biodistribution and associated brain perfusion parameters
      were studied in human brain metastasis as key parameters for treatment
      feasibility and quality. Twelve patients received an intravenous bolus of
      iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state
      infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine
      during the treatment. Absolute iodine concentrations and quantitative perfusion
      maps were derived from 40 multislice dynamic computed tomography (CT) images of
      the brain. The postinfusion mean intratumoral iodine concentration (over 30
      minutes) reached 1.94 +/- 0.12 mg/mL. Reasonable correlations were obtained
      between these concentrations and the permeability surface area product and the
      cerebral blood volume. To our knowledge, this is the first quantitative study of
      CA biodistribution versus time in brain metastasis. The study shows that suitable
      and stable amounts of iodine can be reached for contrast-enhanced radiotherapy.
      Moreover, the associated perfusion measurements provide useful information for
      the patient recruitment and management processes.

PMID- 24447952
TI  - PET imaging of ischemia-induced impairment of mitochondrial complex I function in
      monkey brain.
AB  - To assess the capability of (18)F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)
      ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ((18)F-BCPP-EF), a novel positron
      emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, as a
      specific marker of ischemia-induced neuronal death without being disturbed by
      inflammation, translational research was conducted using an animal PET in
      ischemic brains of Cynomolgus monkeys (Macaca fascicularis). Focal ischemia was
      induced by the right middle cerebral artery occlusion for 3 hours, then PET scans
      were conducted at Day-7 with (15)O-gases for regional cerebral blood flow (rCBF)
      and regional cerebral metabolism of oxygen (rCMRO2), and (18)F-BCPP-EF for MC-I
      with arterial blood sampling. On Day-8, the additional PET scans conducted with
      (11)C-flumazenil ((11)C-FMZ) for central-type benzodiazepine receptors, (11)C
      PBR28 for translocator protein, and (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG)
      for regional cerebral metabolic rate of glucose (rCMRglc). The total distribution
      volume (VT) values of (18)F-BCPP-EF showed the significant reduction in MC-I
      activity in the damaged area at Day-7. When correlated with rCBF and rCMRO2, the
      VT values of (18)F-BCPP-EF provided better correlation with rCMRO2 than with
      rCBF. In the inflammatory regions (region of interest, ROIPBR) of the ischemic
      hemisphere detected with (11)C-PBR28, higher (18)F-FDG uptake and lower VT of
      (18)F-BCPP-EF, (11)C-FMZ, and rCMRO2 than those in normal contralateral
      hemisphere were observed. These results strongly suggested that (18)F-BCPP-EF
      could discriminate the neuronal damaged areas with neuroinflammation, where (18)F
      FDG could not owing to its high uptake into the activated microglia.

PMID- 24447954
TI  - Disinfection of biologically treated wastewater and prevention of biofouling by
      UV/electrolysis hybrid technology: influence factors and limits for domestic
      wastewater reuse.
AB  - Reuse of wastewater contributes significantly to an efficient and sustainable
      water usage. However, due to the presence of a multitude of pathogens (e.g.
      bacteria, viruses, worms, protozoa) in secondary effluents, disinfection
      procedures are indispensable. In decentralized wastewater treatment, UV
      irradiation represents one of the most common disinfection methods in addition to
      membrane processes and to a certain extent electrochemical procedures. However,
      the usage of UV disinfected secondary effluents for domestic (sanitary) or
      irrigation purposes bears a potential health risk due to the possible photo and
      dark repair of reversibly damaged bacteria. Against this background, the
      application of the UV/electrolysis hybrid technology for disinfection and
      prevention of bacterial reactivation in biologically treated wastewater was
      investigated in view of relevant influence factors and operating limits.
      Furthermore, the influence of electrochemically generated total oxidants on the
      formation of biofilms on quartz glass surfaces was examined, since its preventive
      avoidance contributes to an enhanced operational safety of the hybrid reactor. It
      was found that reactivation of bacteria in UV irradiated, biologically treated
      wastewater can be prevented by electrochemically produced total oxidants. In this
      regard, the influence of the initial concentration of the microbiological
      indicator organism Escherichia coli (E. coli) (9.3*10(2)-2.2*10(5) per 100 mL)
      and the influence of total suspended solids (TSS) in the range of 11-75 mg L(-1)
      was examined. The concentration of total oxidants necessary for prevention of
      bacterial regrowth increases linearly with the initial E. coli and TSS
      concentration. At an initial concentration of 933 E. coli per 100 mL, a total
      oxidants concentration of 0.4 mg L(-1) is necessary to avoid photo reactivation
      (at 4200 Lux), whereas 0.67 mg L(-1) is required if the E. coli concentration is
      enhanced by 2.4 log levels (cTSS = constant = 13 mg L(-1)). The prevention of
      dark repair is ensured with 25-50% lower concentration of total oxidants. An
      increase of the TSS concentration from 11 mg L(-1) to 75 mg L(-1) leads to a
      triplication of the need of total oxidants from 0.6 mg L(-1) to 1.8 mg L(-1)
      (3*10(5)E. coli per 100 mL). The energy consumption of the hybrid reactor varies
      from 0.17 kWh m(-3) to 0.94 kWh m(-3) depending on the TSS concentration (11-75
      mg L(-1)). Furthermore, biofilm formation on quartz glass surfaces, of which the
      sleeves of UV lamps consist, can be suppressed by electrochemically produced
      total oxidants at a concentration of at least 1 mg L(-1) which ensures high
      operational safety of the hybrid reactor combined with large maintenance
      intervals. 

PMID- 24447955
TI  - Experimental investigation of a local recirculation photobioreactor for mass
      cultures of photosynthetic microorganisms.
AB  - The present work deals with the experimental fluid mechanics analysis of a wavy
      bottomed cascade photobioreactor, to characterize the extent and period of
      recirculatory and straight-flowing streams establishing therein as a function of
      reactor inclination and liquid flow rate. The substream characterization via
      Feature Tracking (FT) showed that a local recirculation zone establishes in each
      vane only at inclinations <=6 degrees  and that its location changes from the
      lower (<=3 degrees ) to the upper part of each vane (6 degrees ). A straight
      flowing stream flows opposite (above or below) the local recirculation stream.
      The recirculation time ranges from 0.86 s to 0.23 s, corresponding, respectively,
      to the minimum flow rate at the minimum inclination and to the maximum flow rate
      at the maximum inclination where recirculation was observed. The increase of
      photosynthetic activity, resulting from the entailed "flash effect", was
      estimated to range between 102 and 113% with respect to equivalent tubular and
      bubble column photobioreactors. 

PMID- 24447953
TI  - Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac
      arrest.
AB  - We previously showed that inhibition of protein kinase C delta (PKCdelta)
      improves brain perfusion 24 hours after asphyxial cardiac arrest (ACA) and
      confers neuroprotection in the cortex and CA1 region of the hippocampus 7 days
      after arrest. Therefore, in this study, we investigate the mechanism of action of
      PKCdelta-mediated hypoperfusion after ACA in the rat by using the two-photon
      laser scanning microscopy (TPLSM) to observe cortical cerebral blood flow (CBF)
      and laser Doppler flowmetry (LDF) detecting regional CBF in the presence/absence
      of deltaV1-1 (specific PKCdelta inhibitor), nitric oxide synthase (NOS) substrate
      (L-arginine, L-arg) and inhibitor (N(omega)-Nitro-L-arginine, NLA), and nitric
      oxide (NO) donor (sodium nitroprusside, SNP). There was an increase in regional
      LDF and local (TPLSM) CBF in the presence of deltaV1-1+L-arg, but only an
      increase in regional CBF under deltaV1-1+SNP treatments. Systemic blood nitrite
      levels were measured 15 minutes and 24 hours after ACA. Nitrite levels were
      enhanced by pretreatment with deltaV1-1 30 minutes before ACA possibly
      attributable to enhanced endothelial NOS protein levels. Our results suggest that
      PKCdelta can modulate NO machinery in cerebral vasculature. Protein kinase C
      delta can depress endothelial NOS blunting CBF resulting in hypoperfusion, but
      can be reversed with deltaV1-1 improving brain perfusion, thus providing
      subsequent neuroprotection after ACA.

PMID- 24447956
TI  - Alkaptonuric ochronosis: a clinical study from Ardabil, Iran.
AB  - OBJECTIVE: Ochronosis is a term used to describe pigment deposition that occurs
      in the connective tissues of patients with alkaptonuria, an autosomal recessive
      disorder that results from a deficiency of homogentisic acid oxidase. Brown or
      blue-gray discoloration of the skin may be seen on the axillary and inguinal
      areas, face, palms or soles. In addition, blue-black discoloration can be
      apparent on skin overlying cartilage in which the pigment is deposited, such as
      the ears. The sclerae are also typically involved. The cheapest screening test to
      perform prior to expensive lab tests is the urine oxidation test: having it
      standing in light for a period of 24 h when suspicion has risen. METHODS:
      Retrospective analysis of patients with ochronotic arthropathy seen between
      September 2011 to September 2013 was carried out. RESULTS: Seven patients (four
      male, three female) with ochronotic arthropathy were seen, their mean age was
      46.1 years. All patients had bluish-black pigmentations of the ear cartilage and
      sclera. Spondylosis was seen in all, whereas peripheral arthritis was present in
      five patients. Moderate aortic insufficiency and calcification of the aortic
      valve was detected in one male patient. Urine screening for homogentisic acid was
      positive in all seven patients. CONCLUSION: Alkaptonuria is a rare autosomal
      recessive disorder of the metabolism caused by deficiency of homogentisic acid
      oxidase. It is suggested that more widespread screening should be undertaken in
      order to assess the true incidence of the disorder.

PMID- 24447957
TI  - Role of PTGS2-generated PGE2 during gonadotrophin-induced bovine oocyte
      maturation and cumulus cell expansion.
AB  - Prostaglandin E2 (PGE2) is an autocrine/paracrine factor which mediates
      gonadotrophin (Gn) stimulation of cumulus expansion and oocyte maturation in
      rodents. Its role in bovine oocyte maturation is less characterized. This study
      detected PTGS2 (COX2) and PGE synthases (PTGES1, PTGES2 and PTGES3) in bovine
      cumulus-oocyte complexes (COC). Only PTGS2 and PTGES1 expression changed during
      maturation. In Gn-free media, no cumulus expansion and ~45% nuclear maturation
      was achieved, while Gn-induced maturation showed full cumulus expansion (score 3)
      and ~87% maturation. PGE2 supplementation without Gn induced mild cumulus
      expansion (score 0.5-1) but increased nuclear maturation to levels similar to
      those obtained with Gn alone. In the presence of Gn, exogenous PGE2 did not
      affect expansion or nuclear maturation and subsequent embryo development.
      Treatment with PTGS2 selective inhibitor (NS398), PTGS2-specific siRNA or PTGER2
      receptor antagonist (AH6809) resulted in ~20-25% reduction in nuclear maturation.
      NS398 and AH6809 did not affect cumulus expansion. Most oocytes not reaching
      metaphase of second meiosis (MII) following NS398, AH6809 and PTGS2-specific
      siRNA treatments were at MI. After longer maturation, NS398-treated oocytes had
      normal MII rate and uncompromised embryo development. PGE2 has a limited role in
      cumulus expansion in bovine COC but is important for the timing of Gn-induced
      nuclear maturation. We confirmed that genes involved in the synthesis of
      prostaglandin E2 (PGE2) are expressed by cumulus-oocyte complexes (or eggs) of
      cows and that PGE2 is synthesized during oocyte maturation in the presence of
      gonadotrophin hormones. When we inhibited synthesis of PGE2 or blocked its
      receptors, oocyte maturation, but not cumulus expansion, was compromised. Further
      investigation showed that oocyte maturation is delayed but not arrested when PGE2
      synthesis is inhibited. On the other hand, addition of exogenous PGE2 induced a
      high maturation rate and mild cumulus expansion only in the absence of
      gonadotrophin stimulation, and had no effect in the presence of gonadotrophin. 

PMID- 24447958
TI  - Assessment of endometrial and subendometrial blood flow in women undergoing
      frozen embryo transfer cycles.
AB  - This study evaluated whether 3D power Doppler (3DPD) indices from endometrium and
      subendometrium can identify increases in endometrial volume/vascularity induced
      by exogenous oestradiol and subsequent introduction of progestogens in women
      undergoing frozen-thawed embryo transfer (FET). Oral oestradiol was administered
      at increasing doses after down-regulation to prepare the endometrium and
      progestogens were used for luteal support. 3DPD data sets were acquired at down
      regulation, on days 5, 10 and 15 of oestradiol administration and at the time of
      FET. Endometrial thickness was measured using the multiplanar method and
      endometrial volume and blood flow from the endometrium and subendometrium were
      estimated using virtual organ computer-aided analysis and shell-imaging. This
      study evaluated 45 women at least once: 19 achieved clinical pregnancy (CP); 21
      were evaluated at down-regulation (eight CP), 26 at day 5 (10 CP), 31 at day 10
      (12 CP), 31 at day 15 (13 CP) and 16 at FET (seven CP). Changes were observed in
      all parameters between the examinations; however, differences between women who
      achieved CP and those who did not were not significant. 3DPD angiography is not a
      sufficiently sensitive tool to predict the outcome of FET. We evaluate whether 3D
      ultrasound using power Doppler (3DPD) indices from endometrium and subendometrium
      can identify predictable increases in endometrial volume and vascularity induced
      by serial increments in exogenous oestradiol and the subsequent introduction of
      progestogens in women undergoing frozen-thawed embryo transfer (FET) using
      hormone replacement therapy to prepare the endometrium. Oral oestradiol was
      administered at increasing doses after down-regulation to prepare the endometrium
      and progestogens were used for luteal support. 3DPD data sets of the uterus were
      acquired at down-regulation, on days 5, 10, and 15 of oestradiol administration,
      and at the time of FET. Endometrial thickness was measured. Endometrial volume
      and blood flow from the endometrium and subendometrium were measured using
      virtual organ computer-aided analysis (VOCAL) and shell imaging. This study
      evaluated 45 women at least once: 19 achieved clinical pregnancy (CP); 21 were
      evaluated at down-regulation (eight CP), 26 at day 5 (10 CP), 31 at day 10 (12
      CP), 31 at day 15 (13 CP) and 16 at FET (seven CP). Changes were observed in all
      the parameters between the examinations; however, differences between women who
      achieved CP and those who did not were not significant, suggesting that
      quantitative 3D power Doppler angiography is not a sufficiently sensitive tool to
      predict the outcome of FET treatment. 

PMID- 24447959
TI  - Luteal-phase support in assisted reproduction treatment: real-life practices
      reported worldwide by an updated website-based survey.
AB  - An updated worldwide web-based survey assessed the real-life clinical practices
      regarding luteal-phase supplementation (LPS) in assisted reproduction. This
      survey looked for changes since a former survey conducted nearly 3years earlier.
      The survey questions were: If you support the luteal phase, when do you start the
      regimen you are using?; Which agent/route is your treatment of choice to support
      the luteal phase?; If you use vaginal progesterone, which formulation do you
      use?; and How long you continue progesterone supplementation if the patient
      conceived? Data were obtained from 408 centres (82 countries) representing
      284,600 IVF cycles/year. The findings were: (i) most practitioners (80% of
      cycles) start LPS on the day of egg collection; (ii) in >90%, a vaginal
      progesterone product is used (77% as a single agent and 17% in combination with
      i.m. progesterone), while human chorionic gonadotrophin as a single agent for LPS
      is not being used at all; and (iii) in 72% of cycles, LPS is administered until 8
      10weeks' gestation or beyond. When compared with the initial survey, the results
      of this survey are encouraging as there is a clear shift towards a more unified
      and evidence-based approach to LPS in IVF cycles. This updated worldwide web
      based survey assessed the actual real-life clinical practices regarding luteal
      phase supplementation (LPS) in assisted reproduction. Specifically, this survey
      looked for changes since an initial survey conducted nearly 3years earlier. The
      survey included the following questions: If you support the luteal phase, when do
      you start the regimen you are using?; Which agent/route is your treatment of
      choice to support the luteal phase?; If you use vaginal progesterone, which
      formulation do you use?; and How long you continue progesterone supplementation
      if the patient conceived? Data from 408 centres in 82 countries representing a
      total of 284,600 IVF cycles/year were included. Most practitioners (80% of
      cycles) start LPS on the day of egg collection and in more than 90% a vaginal
      progesterone product is used for LPS (in 77% as a single agent and in 17% in
      combination with i.m. progesterone). As a single agent for LPS, human chorionic
      gonadotrophin is not being used at all. Regarding the duration of
      supplementation, in 72% of cycles, LPS is administered until 8-10weeks' gestation
      or beyond. When compared with the initial survey from 2009, the results of this
      updated survey are encouraging as there is a clear shift towards a more unified
      and evidence-based approach to luteal-phase support in IVF cycles. Nevertheless,
      although there is no firm evidence supporting the continuation of LPS after the
      demonstration of fetal heart beat on ultrasound, this remains the common practice
      of the majority of assisted reproduction centres worldwide. 

PMID- 24447960
TI  - Strengths and pitfalls of Canadian gamete and embryo donor registries: searching
      for beneficent solutions.
AB  - For the gamete and embryo donation community, it is well recognized that the
      implementation of a gamete and embryo donor registry (GEDR) represents a good
      initiative to ensure the best possible health conditions for donor-conceived
      individuals. Be they national, institutional or independent, GEDR can play a
      major role in the transmission of health-related genetic and medical information.
      However, from a bioethical analysis standpoint, GEDR raise many questions
      regarding the extent of their beneficent nature. Based on the recent Canadian
      GEDR aborted attempt, this article will focus on bioethical issues and paradoxes
      that can impact the wellbeing of donor-conceived individuals, half-siblings,
      donors and parents. On one hand, the implementation of a GEDR can be ethically
      justified as a beneficent action towards lessening harm associated with the
      transmission of hereditary disease and increasing the effectiveness of preventive
      and therapeutic approaches. On the other hand, examined through the concept of
      nonpaternalistic beneficence, GEDR challenge us to recognize beneficiaries' free
      agency, as well as the importance to transmit reliable and pertinent information.
      Ultimately, beyond an individualistic application of the principle of
      beneficence, socioethics invite us to consider consistency with societal values
      as a prerequisite for achieving a common good. Because the issue of whether or
      not to protect the donor's anonymity occupies the forefront of the discussion
      surrounding gamete and embryo donation, there is less interest in other
      initiatives, which may be implemented to ensure the best possible medical and
      psychosocial conditions for donor-conceived individuals. In this article, we
      propose a bioethical analysis of the use of gamete and embryo donor registries
      (GEDR) from the angle of the principle of beneficence. More specifically, we will
      concentrate on the Canadian situation regarding GEDR. We will look at the
      strengths and pitfalls of this mechanism and suggest a solution to maximize the
      benefits of a GEDR. Many have suggested that such an initiative could have a
      beneficial impact on the wellbeing of donor-conceived individuals, half-siblings,
      donors and parents, by ensuring the constant flow of health-related medical and
      genetic information. As self-evident as the social acceptability of a GEDR may
      seem, we wish to show the limitations of the benefits that a registry is supposed
      to provide. We argue that a GEDR has to do more than simply transmit health
      related information between parties. It also has to be based on pertinent and
      reliable data, be useful for health promotion and recognize beneficiaries' free
      agency. Ultimately, the implementation of a GEDR has to take into consideration
      wider social values. 

PMID- 24447961
TI  - Chromosomal complement and clinical relevance of multinucleated embryos in PGD
      and PGS cycles.
AB  - The objective of this retrospective study was to investigate the incidence and
      clinical implications of multinucleation in blastomeres biopsied from cleavage
      stage embryos obtained from patients undergoing preimplantation genetic screening
      (PGS) for aneuploidies or preimplantation genetic diagnosis (PGD) for
      translocations or single-gene defects (SGD). A total of 3515 embryos were
      obtained from 306 couples in 380 PGD or PGS cycles. Incidence of multinucleation,
      chromosomal complement in multinucleated (MN) and sibling embryos and the
      characteristics of MN embryos resulting in healthy births were investigated. Of
      all cycles, 41.3% involved at least one MN embryo. There were more uniformly
      diploid than uniformly haploid nuclei (22.0% versus 7.9%, P<0.01). The most
      common form of abnormality was chaotic chromosomal complement (39.9%, 147/368).
      Transfer of embryos that had MN blastomeres free of the genetic abnormalities
      tested resulted in three healthy deliveries. It is concluded that, although the
      majority of MN blastomeres are chromosomally abnormal, healthy births are
      possible after transfer of embryos containing these blastomeres subjected to
      genetic analysis. As far as is known, this is the first report of healthy births
      after transfer of embryos with MN blastomeres tested for translocations or SGD in
      PGD cycles. Preimplantation genetic diagnosis (PGD) is an established method for
      selecting genetically healthy embryos for transfer. A blastomere sampled from the
      developing embryo is subjected to genetic analysis. Some of these blastomeres may
      contain multiple nuclei, complicating the genetic diagnosis. We investigated
      clinical implications of multinucleation in PGD cycles. Our results indicate that
      majority of the multinucleated blastomeres, and consequently embryos, are
      genetically abnormal. However, healthy births are possible after transfer of
      multinucleated embryos that are free of the genetic abnormalities screened. 

PMID- 24447962
TI  - Text messaging to support off-campus clinical nursing facilitators: a descriptive
      survey.
AB  - BACKGROUND: Managing large student cohorts can be a challenge for university
      academics, coordinating these units. Bachelor of Nursing programmes have the
      added challenge of managing multiple groups of students and clinical facilitators
      whilst completing clinical placement. Clear, time efficient and effective
      communication between coordinating academics and clinical facilitators is needed
      to ensure consistency between student and teaching groups and prompt management
      of emerging issues. METHODS: This study used a descriptive survey to explore the
      use of text messaging via a mobile phone, sent from coordinating academics to off
      campus clinical facilitators, as an approach to providing direction and support.
      RESULTS: The response rate was 47.8% (n=22). Correlations were found between the
      approachability of the coordinating academic and clinical facilitator perception
      that, a) the coordinating academic understood issues on clinical placement
      (r=0.785, p<0.001), and b) being part of the teaching team (r=0.768, p<0.001).
      Analysis of responses to qualitative questions revealed three themes: connection,
      approachability and collaboration. CONCLUSIONS: This study demonstrates that use
      of regular text messages improves communication between coordinating academics
      and clinical facilitators. Findings suggest improved connection, approachability
      and collaboration between the coordinating academic and clinical facilitation
      staff.

PMID- 24447963
TI  - Development and application to clinical practice of a validated HPLC method for
      the analysis of beta-glucocerebrosidase in Gaucher disease.
AB  - The main objective of our study is to develop a simple, fast and reliable method
      for measuring beta-glucocerebrosidase activity in Gaucher patients leukocytes in
      clinical practice. This measurement may be a useful marker to drive dose
      selection and early clinical decision making of enzyme replacement therapy. We
      measure the enzyme activity by high-performance liquid chromatography with
      ultraviolet detection and 4-nitrophenyl-beta-d-glucopyranoside as substrate. A
      cohort of eight Gaucher patients treated with enzyme replacement therapy and ten
      healthy controls were tested; median enzyme activity values was 20.57mU/ml
      (interquartile range 19.92-21.53mU/ml) in patients and mean was 24.73mU/ml (24.12
      25.34mU/ml) in the reference group, which allowed the establishment of the normal
      range of beta-glucocerebrosidase activity. The proposed method for leukocytes
      glucocerebrosidase activity measuring is fast, easy to use, inexpensive and
      reliable. Furthermore, significant differences between both populations were
      observed (p=0.008). This suggests that discerning between patients and healthy
      individuals and providing an approach to enzyme dosage optimization is feasible.
      This method could be considered as a decision support tool for clinical
      monitoring. Our study is a first approach to in depth analysis of enzyme
      replacement therapy and optimization of dosing therapies. 

PMID- 24447965
TI  - Measures for Level of Functioning and Quality of Life in People with Vestibular
      Disorders. Introduction.

PMID- 24447964
TI  - LC-MS/MS quantitative analysis of paclitaxel and its major metabolites in serum,
      plasma and tissue from women with ovarian cancer after intraperitoneal
      chemotherapy.
AB  - A method for determination of the antineoplastic drug paclitaxel and its main
      metabolites (viz. 6alpha-hydroxypaclitaxel and p-3'-hydroxypaclitaxel) at the sub
      ng/ml level is here presented. Sample preparation consisted of a liquid-liquid
      extraction step for cleanup and preconcentration of the target analytes prior to
      chromatographic analysis by tandem mass spectrometry detection (LC-ESI-MS/MS).
      The determination step was optimized by selected reaction monitoring (SRM) mode
      for highly selective identification and sensitive quantitation of paclitaxel and
      its metabolites in human serum, plasma and tissue. The detection limits were in
      the range 0.03-0.15ng/ml for serum and 0.07-0.62ng/g for tissue, with intra-day
      variability range from 0.5 to 2.7%, expressed as relative standard deviation. The
      method was applied to determine paclitaxel and its metabolites in serum and
      tissue from 13 women suffering from ovarian peritoneal carcinomatosis, after
      hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) treatment. The
      method reported here can be considered a suited tool to monitor the concentration
      of this drug in patients subjected to HIPEC as strategy to evaluate the toxicity
      and efficiency of this treatment. 

PMID- 24447966
TI  - Discussion of the dizziness handicap inventory.
AB  - PURPOSE: A review of the Dizziness Handicap Inventory (DHI). NUMBER OF STUDIES:
      Seventy-four studies. MATERIALS/METHODS: Articles published between January 1990
      and May 2012 were identified by searches in PubMed electronic database. Of the
      227 articles meeting the inclusion criteria 74 were reviewed. These articles are
      discussed under nine topics; Reliability, validity and internal consistency of
      the original version of DHI, relationship between vestibular/balance tests and
      DHI, association between DHI and the other scales related to balance impairments,
      exploratory factor analysis of the DHI, screening version of DHI, translations of
      DHI into other languages, the role of DHI to assess the success of the treatment
      of balance disorder, DHI results in various vestibular disorders, general
      characteristics of DHI in patients with balance impairment. CONCLUSIONS: Self
      reported measures represent unique pieces of the information important for the
      management of dizzy patients. DHI is the most widely used self reported
      measurement of patients with dizziness. It has been translated into fourteen
      languages, so it is widely accepted.

PMID- 24447967
TI  - The University of California Los Angeles Dizziness Questionnaire: advantages and
      disadvantages.
AB  - Dizziness is one of the most troublesome symptoms of vestibular disorders,
      although its description remains somewhat imprecise, encompassing vertigo,
      lightheadedness, disequilibrium and giddiness. Symptoms include sensitivity to
      motion stimuli and discomfort with open spaces, such as empty streets and
      bridges. It is accompanied by varying degrees of anxiety and phobic behaviors.
      Several tools have been developed in an attempt to quantify the degree of
      disability, self-perceived health status and quality of life in patients with
      dizziness. This review focuses on the University of California, Los Angeles
      Dizziness Questionnaire (UCLA-DQ), which is used to assess the effect of
      dizziness on quality of life. This paper also includes a summary of the
      advantages and disadvantages of the UCLA-DQ and compares it to other instruments
      used to assess dizziness. In spite of a few disadvantages, we believe that this
      multidimensional questionnaire is an appropriate tool for evaluating patients
      with vestibular impairment. It should be used during the acute phase of symptoms,
      as well as during and after rehabilitative therapy, to assess patient
      improvement. 

PMID- 24447969
TI  - Introduction to the international classification of functioning disability and
      health - ICF - in the context of vestibular rehabilitation.
AB  - Vestibular rehabilitation focuses at decreasing the impact of symptoms, such as
      vertigo dizziness and imbalance have on people's daily life and their role in
      society. The international Classification of Functioning Disability and Health -
      ICF offers a unified and standard language and framework for describing health
      and health related states. The ICF aims at facilitating communication information
      about health, like functioning and disability. For this purpose the ICF has a
      systematic coding scheme for health data with more than 1400 categories. The big
      number of categories is impractical to apply in a specific area like vestibular
      disorders. Therefore a narrowing down to the relevant categories in a
      comprehensive core set for vertigo (100 categories) and a brief core set (29
      categories) were developed. The purpose of this article is to reflect on the
      potential use of ICF in vestibular rehabilitation. 

PMID- 24447970
TI  - Using core sets of the international classification of functioning, disability
      and health (ICF) to measure disability in vestibular disorders: study protocol.
AB  - Symptom frequency and severity in vestibular disorders often do not correlate
      well with patients' restrictions of activities of daily living and limitations of
      participation. Due to the lack of appropriate patient reported outcome measures
      (PRO), the extent of limitations and restrictions is mostly unknown. The
      International Classification of Functioning, Disability and Health (ICF) is a
      conceptual framework and classification to evaluate all aspects of health and
      disability. An ICF-based measure, the Vestibular and Participation Measure (VAP),
      was recently proposed. Also, an ICF Core Set for vertigo, dizziness and balance
      disorders was developed to describe what aspects of functioning should be
      measured. This study protocol describes the development and cross-cultural
      validation of a new measure, the VAP-extended (VAP-e), based on VAP and ICF Core
      Set on three continents. To determine objectivity and cross-cultural validity of
      the VAP and to find potentially redundant items, Rasch models will be used. The
      VAP-e will be created by modifying or adding items from the Activities and
      Participation and Environmental Factors component of the ICF Core Set.
      Reliability, objectivity and responsiveness of the VAP-e will be tested. 

PMID- 24447968
TI  - Effects of distance and duration on vertical dynamic visual acuity in screening
      healthy adults and people with vestibular disorders.
AB  - BACKGROUND: Dynamic visual acuity (DVA) testing may be a useful, indirect
      indicator of vestibulo-ocular reflex function. Previous evidence shows that
      acuity for 2 m targets differs little between patients and normals using a 75 ms
      display duration and that healthy subjects do not differ in acuity when standing
      and walking while viewing a far target but they do differ when viewing a near
      target. OBJECTIVE: Improve the protocol of a screening tool by testing the
      hypothesis that healthy control subjects and patients and with unilateral
      peripheral vestibular weakness differ on DVA when viewing far targets while
      seated. METHODS: Controls and patients were tested while they were seated in a
      chair that oscillated vertically at 2 Hz. They viewed a computer screen 4 m away,
      while stationary and while moving, with viewing times of either 75 ms or 500 ms.
      RESULTS: The amount of change between static and dynamic conditions did not
      differ significantly between patients and controls for the 75 ms condition but
      controls had lower difference scores than patients when using the 500 ms
      duration. The ROC value was low, 0.68. Compared to historical data using the 75
      ms duration at a distance of 2 m, subjects in both diagnostic groups had better
      visual acuity at the 75 ms/4 m distance. CONCLUSIONS: These results suggest that
      using the longer duration is better for differentiating patients from healthy
      controls and they support previous evidence showing that near target viewing is
      more challenging.

PMID- 24447971
TI  - The vestibular activities and participation measure and vestibular disorders.
AB  - Vestibular disorders are commonly reported health conditions that lead to
      debilitating consequences. Activity limitations and participation restrictions
      are the main disabling consequences of vestibular disorders. Measuring activities
      and participation in people with vestibular disorders has been a challenge due to
      the absence of specialized outcome measures that quantify activities and
      participation based on a standardized framework such as the International
      Classification of Functioning, Disability and Health (ICF). The Vestibular
      Activities and Participation (VAP) questionnaire was developed to quantify
      activity limitations and participation restrictions in people with balance and
      vestibular disorders. Of the 34 items included in the VAP, 29 (85%) of the items
      had at least 25% or more of the respondents report that they had moderate to
      severe difficulty and 10 items had 40% or more of the participants report that
      they had difficulty with the activity or participation item. The psychometric
      properties of the VAP were examined and demonstrated very good reliability and
      validity in persons with balance and vestibular dysfunction and may be helpful in
      identifying activity and participation limitations. 

PMID- 24447974
TI  - The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid
      function.
AB  - Quercetin is the most abundant flavonoid present in a broad range of fruit and
      vegetables. Furthermore, quercetin is available as dietary supplements that are
      based on its antioxidant, antiproliferative and anti-inflammatory properties.
      However, concerns have been raised about the potential toxic effects of excessive
      intake of quercetin, and several studies have demonstrated that flavonoids,
      included quercetin, can interfere with thyroid function. In a previous report, we
      showed that quercetin inhibits thyroid-cell growth and iodide uptake. The latter
      effect was associated with down-regulation of sodium/iodide symporter gene
      expression. In the present study, we have evaluated the effects of quercetin on
      the expression of other thyroid-restricted genes, and we show that quercetin
      decreases the expression of the thyrotropin receptor, thyroid peroxidase and
      thyroglobulin genes. We further investigated the inhibitory effects of quercetin
      on thyroid function in vivo through evaluation of radioiodine uptake in the
      Sprague-Dawley rat, which was significantly decreased after 14 days of quercetin
      treatment. These data confirm that quercetin can act as a thyroid disruptor, and
      they suggest that caution is needed in its supplemental and therapeutic use.

PMID- 24447975
TI  - Antimutagenic and antiherpetic activities of different preparations from Uncaria
      tomentosa (cat's claw).
AB  - Uncaria tomentosa have been used to treat viral diseases such as herpes due to
      multiple pharmacological effects, but its therapeutic efficacy against this virus
      have not been reported yet. Thus, in vitro antiherpetic activity of
      hydroethanolic extract from barks, purified fractions of quinovic acid glycosides
      and oxindole alkaloids was evaluated by plaque reduction assay, including
      mechanistic studies (virucidal, attachment and penetration action). Once exposure
      to physical agents might lead to reactivation of the herpetic infection,
      antimutagenic effect (pre-, simultaneous and post-treatment protocols) was also
      evaluated by Comet assay. The antiherpetic activity from the samples under
      investigation seemed to be associated with the presence of polyphenols or their
      synergistic effect with oxindole alkaloids or quinovic acid glycosides, once both
      purified fractions did not present activity when evaluated alone. Inhibition of
      viral attachment in the host cells was the main mechanism of antiviral activity.
      Although both purified fractions displayed the lowest antimutagenic activity in
      pre and simultaneous treatment, they provided a similar effect to that of cat's
      claw hydroethanolic extract in post-treatment. Given that purified fractions may
      result in a reduced antiherpetic activity, the use of cat's claw hydroethanolic
      extract from barks should be prioritized in order to obtain a synergistic effect.

PMID- 24447976
TI  - Probabilistic assessment of exposure to nail cosmetics in French consumers.
AB  - The aim of this study was to assess probabilistic exposure to nail cosmetics in
      French consumers. The exposure assessment was performed with base coat, polish,
      top coat and remover. This work was done for adult and child consumers. Dermal,
      inhalation and oral routes were taken into account for varnishes. Exposure
      evaluation was performed for the inhalation route with polish remover. The main
      route of exposure to varnishes was the ungual route. Inhalation was the secondary
      route of exposure, followed by dermal and oral routes. Polish contributed most to
      exposure, regardless of the route of exposure. For this nail product, P50 and P95
      values by ungual route were respectively equal to 1.74 mg(kg bw week)(-1) and
      8.55 mg(kg bw week)(-1) for women aged 18-34 years. Exposure to polish by
      inhalation route was equal to 0.70 mg(kg bw week)(-1) (P50) and 5.27 mg(kg bw
      week)(-1) (P95). P50 and P95 values by inhalation route were respectively equal
      to 0.08 mg(kg bw week)(-1) and 1.14 mg(kg bw week)(-1) for consumers aged 18-34
      years exposed to polish remover. This work provided current exposure data for
      nail cosmetics, and a basis for future toxicological studies of the uptake of
      substances contained in nail cosmetics in order to assess systemic exposure.

PMID- 24447977
TI  - Toll-like receptor 4-mediated ROS signaling pathway involved in Ganoderma atrum
      polysaccharide-induced tumor necrosis factor-alpha secretion during macrophage
      activation.
AB  - Ganoderma atrum has been used as Chinese traditional medicine and healthful
      mushroom for thousands of years. The polysaccharide is regarded as the major
      bioactive substances in G. atrum. To delineate the underlying mechanism and
      signaling cascade involved in the immunomodulatory property of G. atrum
      polysaccharide (PSG-1). Specifically, this study is designed to examine the
      possibility of TLR4 as a candidate receptor interacted with G. atrum
      polysaccharide (PSG-1) and elucidate the role of reactive oxygen species (ROS) in
      PSG-1-induced tumor necrosis factor-alpha (TNF-alpha) production during
      macrophage activation. Flow cytometric and confocal laser-scanning microscopy
      analysis showed that fluorescence-labeled PSG-1 bind specifically to the
      macrophages. Moreover, PSG-1 stimulated TNF-alpha secretion of peritoneal
      macrophages from C3H/HeN mice, but not from C3H/HeJ mice. PSG-1-indcued TNF-alpha
      production was suppressed by anti-TLR4 mAb. Furthermore, ROS production was
      mediated by TLR4, and NADPH oxidase-derived ROS act as upstream of
      phosphoinositide 3-kinase(PI3K)/Akt/mitogen-activated protein
      kinases(MAPKs)/nuclear factor(NF)-kappaB signaling pathway in the regulation of
      PSG-1 stimulated TNF-alpha production. Taken together, we conclude that PSG-1
      induces TNF-alpha secretion through TLR4/ROS/PI3K/Akt/MAPKs/NF-kappaB pathways
      during macrophage activation. Our findings provide a molecular basis for the
      potential of PSG-1 as a novel immunomodulatory agent. 

PMID- 24447978
TI  - TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFkappaB-mediated
      inflammation and accelerate Nrf2-induced antioxidative potential through the
      modulation of PI3K-Akt signaling pathway in RAW 264.7 cells.
AB  - Anti-inflammatory and anti-oxidative activities of polysaccharides from Taraxacum
      officinale (TOP 1 and 2) were analyzed in RAW 264.7 cells. First,
      lipopolysaccharide (LPS) was applied to identify anti-inflammatory activity of
      TOPs, which reduced expression of inducible nitric oxide synthase (iNOS) and
      tumor necrosis factor (TNF)-alpha. TOPs treatment inhibited phosphorylation of
      inflammatory transcription factor, nuclear factor (NF)kappaB, and its upstream
      signaling molecule, PI3K/Akt. Second, cytoprotective potential of TOPs against
      oxidative stress was investigated via heme oxygenase (HO)-1 induction. HO-1, one
      of phase II enzymes shows antioxidative activity, was potently induced by TOPs
      treatment, which was in accordance with the nuclear translocation of nuclear
      factor-erythroid 2 p45-related factor 2 (Nrf2). In addition, TOPs treatment
      phosphorylated PI3K/Akt with slight activation of c-Jun NH2-terminal kinase
      (JNK). TOPs-mediated HO-1 induction protected macrophage cells from oxidative
      stress-induced cell death, which was confirmed by SnPP and CoPP (HO-1 inhibitor
      and inducer, respectively). Consequently, TOPs potently inhibited NFkappaB
      mediated inflammation and accelerated Nrf2-mediated antioxidative potential
      through the modulation of PI3K/Akt pathway, which would contribute to their
      promising strategy for novel anti-inflammatory and anti-oxidative agents. 

PMID- 24447979
TI  - Modulation effects of cordycepin on the skeletal muscle contraction of toad
      gastrocnemius muscle.
AB  - Isolated toad gastrocnemius muscle is a typical skeletal muscle tissue that is
      frequently used to study the motor system because it is an important component of
      the motor system. This study investigates the effects of cordycepin on the
      skeletal muscle contractile function of isolated toad gastrocnemius muscles by
      electrical field stimulation. Results showed that cordycepin (20 mg/l to 100
      mg/l) significantly decreased the contractile responses in a concentration
      dependent manner. Cordycepin (50 mg/l) also produced a rightward shift of the
      contractile amplitude-stimulation intensity relationship, as indicated by the
      increases in the threshold stimulation intensity and the saturation stimulation
      intensity. However, the most notable result was that the maximum amplitude of the
      muscle contractile force was significantly increased under cordycepin application
      (122+/-3.4% of control). This result suggests that the skeletal muscle
      contractile function and muscle physical fitness to the external stimulation were
      improved by the decreased response sensitivity in the presence of cordycepin.
      Moreover, cordycepin also prevented the repetitive stimulation-induced decrease
      in muscle contractile force and increased the recovery amplitude and recovery
      ratio of muscle contraction. However, these anti-fatigue effects of cordycepin on
      muscle contraction during long-lasting muscle activity were absent in Ca2+-free
      medium or in the presence of all Ca2+ channels blocker (0.4 mM CdCl2). These
      results suggest that cordycepin can positively affect muscle performance and
      provide ergogenic and prophylactic benefits in decreasing skeletal muscle
      fatigue. The mechanisms involving excitation-coupled Ca2+ influxes are strongly
      recommended.

PMID- 24447980
TI  - BMJ too negative on e-cigarettes.

PMID- 24447981
TI  - Polycystic ovary syndrome in Iranian adolescents.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is linked with metabolic syndrome,
      which includes obesity, insulin resistance, dyslipidemia, and endocrine function
      in patients with PCOS. The aim of this study was to determine the prevalence of
      adolescent PCOS and characteristics associated with PCOS in adolescents in Babol,
      Iran. MATERIALS AND METHODS: A cross-sectional study was conducted on 1549 girl
      high school students aged 16-20 years who were living in Iran. After overnight
      fasting, blood samples were collected to determine hormones and lipid levels in
      PCOS patients between the first and fifth days of their menstrual period or
      withdrawal bleeding. RESULTS: The overall prevalence of adolescent PCOS was 129
      (8.3%) (95% CI; 4.0, 12.0). Irregular menstruation was observed in 24.1% of
      adolescents. A total of 68% of PCOS adolescents had insulin resistance. Compared
      with non-PCOS adolescents, the OR of adolescent PCOS for family history of
      hirsutism was 1.53 (95% CI, 1.06-2.20; p=0.024), family history of irregular
      menstrual cycle was 2.27 (95% CI, 1.56-3.30; p<0.001), menarche age <13 years was
      1.95 (95% CI, 1.36-2.81; p<0.001), hirsutism was 1.14 (CI 95%, 1.10-1.17;
      p<0.001), acne was 5.10 (CI 95%, 3.52-7.40; p<0.001), and wrist circumference was
      1.28 (CI 95%, 1.07-1.54; p=0.007). CONCLUSION: The presenting findings showed the
      high prevalence of PCOS among Iranian adolescents. Emphasis should be placed on
      clinical screening in adolescents with high-risk factors, including irregular
      menstrual, menarche <13 years, hirsutism, acne, high wrist circumference, and
      paternal obesity to help reduce the risk of developing metabolic disturbance and
      to find ways to improve long-term health.

PMID- 24447982
TI  - Factors associated with physical inactivity among female and male rural
      adolescents in Borneo - a cross-sectional study.
AB  - Rural communities have shown marked increase in metabolic syndrome among young
      people, with physical inactivity as one of the main contributing factors. This
      study aimed to determine factors associated with physical inactivity among male
      and female rural adolescents in a sample of schools in Malaysia. A cross
      sectional study was conducted among 145 students aged 13-15 years. Data on socio
      demographic, health-related, and psychosocial factors (perceived barriers, self
      efficacy, social influences) were collected using a self-administered
      questionnaire. Anthropometric measurement was taken to generate body mass index
      (BMI)-for-age, while physical activity (PA) level was assessed using pedometers.
      The mean steps per day was 6251.37 (SD=3085.31) with males reported as being more
      active. About 27% of the respondents were either overweight or obese, with more
      females in this group. There was no significant difference in steps among males
      and females (p=0.212), and nutritional status (BMI-for-age) (p=0.439). Females
      consistently scored higher in most items under perceived barriers, but had
      significantly lower scores in self-efficacy's items. Males were more influenced
      by peers in terms of PA (p<0.001) and were more satisfied with their body parts
      (p=0.047). A significantly higher body size discrepancy score was found among
      females (p=0.034, CI -0.639, -0.026). PA level was low and almost one-third of
      the respondents were overweight and obese. Female students faced more barriers
      and had lower self-efficacy with regards PA. Based on the findings, it is
      recommended that interventions focus on reducing barriers while increasing
      support for PA. This is particularly important in improving the health status of
      the youth, especially among the females.

PMID- 24447983
TI  - Non-medical prescription drug and illicit street drug use among young Swiss men
      and associated mental health issues.
AB  - Non-medical use of prescription drugs (NMUPD) is increasing among the general
      population, particularly among teenagers and young adults. Although prescription
      drugs are considered safer than illicit street drugs, NMUPD can lead to
      detrimental consequences. The aim of the present study was to investigate the
      relationship between drug use (NMUPD on the one side, illicit street drugs on the
      other side) with mental health issues and then compare these associations. A
      representative sample of 5719 young Swiss men aged around 20 years filled in a
      questionnaire as part of the ongoing baseline Cohort Study on Substance Use Risk
      Factors (C-SURF). Drug use (16 illicit street drugs and 5 NMUPDs, including
      sleeping pills, sedatives, pain killers, antidepressants, stimulants) and mental
      health issues (depression, SF12) were assessed. Simple and multiple linear
      regressions were employed. In simple regressions, all illicit and prescription
      drugs were associated with poorer mental health. In multiple regressions, most of
      the NMUPDs, except for stimulants, were significantly associated with poorer
      mental health and with depression. On the contrary, the only associations that
      remained significant between illicit street drugs and mental health involved
      cannabis. NMUPD is of growing concern not only because of its increasing
      occurrence, but also because of its association with depression and mental health
      problems, which is stronger than the association observed between these problems
      and illicit street drug use, excepted for cannabis. Therefore, NMUPD must be
      considered in screening for substance use prevention purposes.

PMID- 24447984
TI  - Awareness of current recommendations and guidelines regarding strength training
      for youth.
AB  - AIM: Physical conditioning of youth has always been a controversial topic as it
      raises ethical, physiological, and medical issues. Current recommendations and
      guidelines suggest that strength training is a relatively safe and worthwhile
      method in conditioning youth. This, however, requires well-informed coaches who
      follow age-appropriate strength training recommendations and guidelines, compiles
      well-designed strength training programs, and provides qualified supervision and
      instructions. The purpose of this study was to investigate coaches' awareness of
      current recommendations and guidelines regarding strength training for youth.
      METHOD: A total of 39 football (US: soccer) coaches (34 males and 5 females)
      training boys in age groups 8-12 years were included in this study. Data were
      collected using an attitude statement questionnaire, and the assertions were
      based upon current recommendations and guidelines. RESULTS: The results revealed
      significant differences among coaches in terms of knowledge of important aspects
      of strength training for youth. CONCLUSIONS: The results suggested that coaches
      in the present study were not aware of the latest recommendations and guidelines
      regarding strength training for youth.

PMID- 24447985
TI  - Gender differences in early trauma and high-risk behaviors among street
      entrenched youth in British Columbia.
AB  - OBJECTIVE: This work aimed to evaluate gender differences among the street
      entrenched youth in British Columbia in terms of their demographics, experiences
      of childhood maltreatment, mental health issues, and substance use behaviors.
      MATERIALS AND METHODS: Data were derived from the BC Health of the Homeless Study
      (BCHOHS), carried out in three cities in British Columbia, Canada. Measures
      included socio-demographic information, the Maudsley Addiction Profile (MAP), the
      Childhood Trauma Questionnaire (CTQ), the Mini International Neuropsychiatric
      Interview (MINI) Plus and the National Survey of Homeless Assistance Providers
      and Clients (NSHAPC)-Health Chapter. RESULTS: Youth constituted 16.5% (n=82) of
      the homeless population. Females (55%) outnumbered males and engaged in survival
      sex more frequently (17.8%; p=0.03). Males had greater substance abuse of alcohol
      (81.1%) and cannabis (89.2%). Depression (p=0.02) and psychosis (p=0.05) were
      more common among females, while panic disorder was more common among males
      (p=0.04). Rates of childhood trauma were similar across genders. CONCLUSION: Our
      findings reflect trends among youth where illicit drug use may be similar among
      genders while males may report increased alcohol and cannabis use, possibly as a
      means to self medicate their panic-related symptoms. In any case, this population
      of street entrenched-youth frequently experiences several significant problems
      ranging from childhood abuse to high rates of substance abuse and mental
      illnesses.

PMID- 24447986
TI  - Perspectives of clinical medical directors in child and adolescent psychiatry:
      diagnostic and treatment needs of migrant families.
AB  - Germany is one of many nations characterized by an increasing number of children
      originating from families with a migration background. Medical treatment
      modalities will be required to adjust for diversity of social and cultural
      background. Initiated by the Federal Society of Child and Adolescent Psychiatry
      (BKJPP), representing mainly those psychiatrists working in private practice, and
      by the Federal Working Commission of Medical Directors employed in Child and
      Adolescent Psychiatric Clinics (BAG), a questionnaire was constructed to identify
      mental health professionals' (psychiatrists') evaluation of the needs and quality
      of diagnosis and treatment for migrant families. The current study focused on
      medical directors and deputy chief physicians in clinics for child and adolescent
      psychiatry. Preliminary results of this survey - implementing descriptive
      statistics as well as univariate and multivariate statistical analyses -
      permitted an assessment of the current state of identification and treatment of
      migrant offspring attending child and adolescent psychiatric practices in
      Germany. Recommendations and concrete steps are offered, which aim to promote
      "cultural opening", and assist in health and social policy makers' decisions for
      improved mental health care.

PMID- 24447987
TI  - The context of alcohol consumption among adolescents and their families.
AB  - AIMS: Alcohol consumption in adolescence has been an important topic in the study
      of public health policies. This study aimed to analyze and interpret the
      influence of the family in teenage alcohol consumption. MATERIALS AND METHODS: A
      qualitative research was undertaken, using interviews, observation, genogram and
      eco-map, in order to investigate 22 participants at a Family Health Unit in the
      city of Recife, Pernambuco, Brazil. The family structure, composition,
      interaction, communication, and religion of the participants were considered.
      RESULTS: The results were analyzed using inductive thematic analysis and
      indicated three themes, namely, the internality of the family: fragility and
      conflicts; among us: limits, responsibilities and hope; and the decision to
      drink: fun permeated by risks. CONCLUSION: The family and sociocultural context
      of adolescents can positively and negatively influence the use and abuse of
      alcohol and, therefore, can be a target of intervention in nursing.

PMID- 24447989
TI  - Editorial.

PMID- 24447988
TI  - Prevalence of health behaviors and their associated factors among a sample of
      university students in India.
AB  - OBJECTIVE: With advances in knowledge about health promotion, public health
      professionals are in search for the determinants of personal health behaviors.
      The purpose of this study was to assess the prevalence of health behaviors and
      its associated factors in a sample of Indian university students. MATERIALS AND
      METHODS: Using a cross-sectional survey, we assessed health behavior among a
      sample of randomly selected university students. The sample included 800
      university students from non-health (mainly engineering and sciences)
      undergraduate courses of Gitam University, Visakhapatnam in India. The students
      were 541 (67.6%) males and 259 (32.4%) females in the age range of 17-20 years
      (Median age=18.2 years, SD=1.0). RESULTS: On average, students engaged in 15.8
      out of 25 health behavior practices. There was a high rate of overweight and
      obesity (26.8% and 10.7%, respectively), low rate of brushing teeth at least
      twice a day (28.6%), annual dental check-up (25.8%), habitual seatbelt use (23%),
      and poor dietary patterns (79% ate less than the recommended fruit and vegetable
      consumption of five servings a day, and 68.5% did not avoid eating fat and
      cholesterol). In multivariate analysis among men, personal constraints (Odds
      Ratio=OR 1.75, Confidence Interval=CI 1.09-2.82), health benefits (OR=2.01,
      CI=1.27-3.17), and not suffering from depression (OR=0.60, CI=0.22-0.94) were
      associated with the health behavior index. Among women, those who were living
      away from their parents or guardians (OR=1.94, CI=1.06-3.55), economically better
      off (OR=2.16, CI=1.00-4.63), and had higher social support (OR=3.65, CI=1.75
      7.63), were associated with the health behavior index. DISCUSSION: Students had a
      high proportion of health behavior practices. Several high health risk practices
      were identified, including overweight, poor dental practices, poor dietary and
      sleeping habits. It is hoped that the gender-specific predictors identified,
      including sociodemographics as well as social and mental health variables, can
      also be utilized in designing health promotion programs.

PMID- 24447990
TI  - Consensus, guidelines and reviews.

PMID- 24447994
TI  - Anaesthesia, amnesia and harm.
AB  - Anaesthesia causes unconsciousness by suppressing neural mechanisms mediating
      arousal and awareness. It also causes amnesia by disrupting mechanisms of memory
      consolidation. Some patients under general anaesthesia unexpectedly become aware
      during surgery and form a traumatic memory of their experience. After describing
      the neural underpinning of phenomenal consciousness and memory, I examine the
      respects in which patients who experience anaesthesia awareness can be harmed by
      it. In cases where awareness is detected intraoperatively, I consider whether an
      anaesthetist would be justified in administering a drug to prevent a memory of
      the experience, as well as reasons for and against preoperatively informing
      patients of the possibility of awareness. In cases where awareness is reported
      postoperatively, I consider reasons for taking a drug to erase a memory of
      awareness against reasons for retaining the memory. A decision to take or decline
      such a drug would be informed by the potential harm of these memories and the
      potential benefits and risks of drugs intended to erase them. 

PMID- 24447995
TI  - Nocturnal frontal lobe epilepsy in mucopolysaccharidosis.
AB  - Nocturnal frontal lobe epilepsy (NFLE) is an epileptic syndrome that is primarily
      characterized by seizures with motor signs occurring almost exclusively during
      sleep. We describe 2 children with mucopolysaccharidosis (MPS) who were referred
      for significant sleep disturbance. Long term video-EEG monitoring (LT-VEEGM)
      demonstrated sleep-related hypermotor seizures consistent with NFLE. No case of
      sleep-related hypermotor seizures has ever been reported to date in MPS. However,
      differential diagnosis with parasomnias has been previously discussed. The high
      frequency of frontal lobe seizures causes sleep fragmentation, which may result
      in sleep disturbances observed in at least a small percentage of MPS patients. We
      suggest monitoring individuals with MPS using periodic LT-VEEGM, particularly
      when sleep disorder is present. Moreover, our cases confirm that NFLE in
      lysosomal storage diseases may occur, and this finding extends the etiologic
      spectrum of NFLE.

PMID- 24447997
TI  - [Lady Windermere syndrome: involvement of the middle lobe and lingula by
      Mycobacterium avium complex].

PMID- 24447996
TI  - Dinophysis toxins: causative organisms, distribution and fate in shellfish.
AB  - Several Dinophysis species produce diarrhoetic toxins (okadaic acid and
      dinophysistoxins) and pectenotoxins, and cause gastointestinal illness,
      Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells.L
      1). They are the main threat, in terms of days of harvesting bans, to aquaculture
      in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very
      variable, more between strains than species. The distribution of DSP events
      mirrors that of shellfish production areas that have implemented toxin
      regulations, otherwise misinterpreted as bacterial or viral contamination. Field
      observations and laboratory experiments have shown that most of the toxins
      produced by Dinophysis are released into the medium, raising questions about the
      ecological role of extracelular toxins and their potential uptake by shellfish.
      Shellfish contamination results from a complex balance between food selection,
      adsorption, species-specific enzymatic transformations, and allometric processes.
      Highest risk areas are those combining Dinophysis strains with high cell content
      of okadaates, aquaculture with predominance of mytilids (good accumulators of
      toxins), and consumers who frequently include mussels in their diet. Regions
      including pectenotoxins in their regulated phycotoxins will suffer from much
      longer harvesting bans and from disloyal competition with production areas where
      these toxins have been deregulated.

PMID- 24447998
TI  - Interclass small leucine-rich repeat proteoglycan interactions regulate collagen
      fibrillogenesis and corneal stromal assembly.
AB  - The corneal stroma is enriched in small leucine-rich proteoglycans (SLRPs),
      including both class I (decorin and biglycan) and class II (lumican, keratocan
      and fibromodulin). Transparency is dependent on the assembly and maintenance of a
      hierarchical stromal organization and SLRPs are critical regulatory molecules. We
      hypothesize that cooperative interclass SLRP interactions are involved in the
      regulation of stromal matrix assembly. We test this hypothesis using a compound
      Bgn(-/0)/Lum(-/-) mouse model and single Lum(-/-) or Bgn(-/0) mouse models and
      wild type controls. SLRP expression was investigated using immuno-localization
      and immuno-blots. Structural relationships were defined using ultrastructural and
      morphometric approaches while transparency was analyzed using in vivo confocal
      microscopy. The compound Bgn(-/0)/Lum(-/-) corneas demonstrated gross opacity
      that was not seen in the Bgn(-/0) or wild type corneas and greater than that in
      the Lum(-/-) mice. The Bgn(-/0)/Lum(-/-) corneas exhibited significantly
      increased opacity throughout the stroma compared to posterior opacity in the Lum(
      /-) and no opacity in Bgn(-/0) or wild type corneas. In the Bgn(-/0)/Lum(-/-)
      corneas there were abnormal lamellar and fibril structures consistent with the
      functional deficit in transparency. Lamellar structure was disrupted across the
      stroma with disorganized fibrils, and altered fibril packing. In addition,
      fibrils had larger and more heterogeneous diameters with an abnormal structure
      consistent with abnormal fibril growth. This was not observed in the Bgn(-/0) or
      wild type corneas and was restricted to the posterior stroma in Lum(-/-) mice.
      The data demonstrate synergistic interclass regulatory interactions between
      lumican and biglycan. These interactions are involved in regulating both lamellar
      structure as well as collagen fibrillogenesis and therefore, corneal
      transparency. 

PMID- 24448000
TI  - CYB5A and autophagy-mediated cell death in pancreatic cancer.
AB  - The highly invasive and chemoresistant phenotype of pancreatic cancer highlights
      the urgency to identify prognostic biomarkers and novel therapeutic targets.
      Recently, we observed a significant correlation between shorter survival and loss
      of the cytoband 18q22.3. Here we investigated genes encoded by this cytoband, and
      demonstrated the prognostic value of CYB5A in resected and metastatic patients.
      Furthermore, our in vitro and in vivo studies clarified CYB5A inhibitory activity
      of oncogenic phenotypes through autophagy induction. This raises the possibility
      that inhibition of CYB5A-deregulated downstream pathways, such as those involving
      TRAF6, may favor autophagy-mediated cancer cell death in selected subgroups of
      patients. 

PMID- 24447999
TI  - A decorin-deficient matrix affects skin chondroitin/dermatan sulfate levels and
      keratinocyte function.
AB  - Decorin is a small leucine-rich proteoglycan harboring a single glycosaminoglycan
      chain, which, in skin, is mainly composed of dermatan sulfate (DS). Mutant mice
      with targeted disruption of the decorin gene (Dcn(-/-)) exhibit an abnormal
      collagen architecture in the dermis and reduced tensile strength, collectively
      leading to a skin fragility phenotype. Notably, Ehlers-Danlos patients with
      mutations in enzymes involved in the biosynthesis of DS display a similar
      phenotype, and recent studies indicate that DS is involved in growth factor
      binding and signaling. To determine the impact of the loss of DS-decorin in the
      dermis, we analyzed the glycosaminoglycan content of Dcn(-/-) and wild-type mouse
      skin. The total amount of chondroitin/dermatan sulfate (CS/DS) was increased in
      the Dcn(-/-) skin, but was overall less sulfated with a significant reduction in
      bisulfated DeltaDiS2,X (X=4 or 6) disaccharide units, due to the reduced
      expression of uronyl 2-O sulfotransferase (Ust). With increasing age, sulfation
      declined; however, Dcn(-/-) CS/DS was constantly undersulfated vis-a-vis wild
      type. Functionally, we found altered fibroblast growth factor (Fgf)-7 and -2
      binding due to changes in the micro-heterogeneity of skin Dcn(-/-) CS/DS. To
      better delineate the role of decorin, we used a 3D Dcn(-/-) fibroblast cell
      culture model. We found that the CS/DS extracts of wild-type and Dcn(-/-)
      fibroblasts were similar to the skin sugars, and this correlated with the lack of
      uronyl 2-O sulfotransferase in the Dcn(-/-) fibroblasts. Moreover, Ffg7 binding
      to total CS/DS was attenuated in the Dcn(-/-) samples. Surprisingly, wild-type
      CS/DS significantly reduced the binding of Fgf7 to keratinocytes in a
      concentration dependent manner unlike the Dcn(-/-) CS/DS that only affected the
      binding at higher concentrations. Although binding to cell-surfaces was quite
      similar at higher concentrations, keratinocyte proliferation was differentially
      affected. Higher concentration of Dcn(-/-) CS/DS induced proliferation in
      contrast to wild-type CS/DS. 3D co-cultures of fibroblasts and keratinocytes
      showed that, unlike Dcn(-/-) CS/DS, wild-type CS/DS promoted differentiation of
      keratinocytes. Collectively, our results provide novel mechanistic explanations
      for the reported defects in wound healing in Dcn(-/-) mice and possibly Ehlers
      Danlos patients. Moreover, the lack of decorin-derived DS and an altered CS/DS
      composition differentially influence keratinocyte behavior. 

PMID- 24448001
TI  - Sorption-desorption and biosorption of bisphenol A, triclosan, and 17alpha
      ethinylestradiol to sewage sludge.
AB  - To better understand the fate of microconstituents (MCs) in an activated sludge
      (AS) system, sorption, biosorption, and desorption studies were investigated at
      MUg/L range for 17alpha-ethinylestradiol (EE2), bisphenol A (BPA), and triclosan
      (TCS). Batch experiments with activated and deactivated sludge originating from
      continuous flow porous pot reactors operating at solid retention times (SRTs) of
      5, 10, and 15 days were conducted in order to investigate the sorption kinetics
      and distinguish physicochemical sorption and biosorption. The effect of SRT and
      the biomass concentration on sorption kinetics were also studied. Selected MCs
      showed high sorption affinity to the non-viable biomass during the first 30 min
      of the experiment, which was gradually reduced until equilibrium was reached.
      Desorption results showed two distinct stages, a very rapid desorption within 20
      min followed by a slow desorption stage. Biosorption study indicated that the
      soluble concentrations of target compounds decreased rapidly for selected MCs
      similar to the sorption study; however, the soluble and solid phase
      concentrations continued to decrease slowly during the length of the experiment
      which indicates the possible biodegradation of these compounds in both phases.
      Finally, mathematical models were applied to describe the sorption mechanism and
      Freundlich sorption isotherms with values of 1/n close to 1 were found to best
      fit the results which demonstrate that all tested concentrations result on the
      linear part of the Freundlich isotherm. Calculation of the Freundlich constant,
      KF and distribution coefficient, Kd exhibited the greater tendency of EE2 and TCS
      for sorption, compared to BPA. The results of this study indicated that the SRT
      had a clear effect on the sorption kinetics where the highest sorption rate
      constant was achieved for a SRT of 10 days for all three target substances. This
      could be due to change of the morphology of the biomass from reactors operating
      at different SRTs.

PMID- 24448002
TI  - Temporal variability of urinary di(2-ethylhexyl) phthalate metabolites during a
      dietary intervention study.
AB  - Exposure to di(2-ethylhexyl) phthalate (DEHP) may be related to adverse health
      effects including developmental and reproductive disorders, prompting interest in
      strategies for reducing human exposure. We previously reported a reduction of
      DEHP metabolite levels in composite urine samples by more than 50% (geometric
      means) during a 3-day dietary intervention avoiding plastics in food packaging,
      preparation, and storage. In the present study, we analyzed individual spot urine
      samples before compositing in order to evaluate temporal variability. There were
      no meaningful changes in any of the previous findings when using individual
      rather than composited samples. Individual urine samples, like the composites,
      showed significant decreases of >=50% in all three measured DEHP metabolites
      during the intervention. Compositing urine samples provided sufficient
      information to observe the effect of the intervention, whereas reducing
      analytical expenses compared with analyzing multiple samples individually. Low
      intraclass correlations (ICCs) for samples collected from the same person before
      the intervention indicate the importance of collecting multiple samples per
      exposure condition. Substantially larger ICCs during and after the intervention
      suggest that much of the variability observed in DEHP metabolite levels
      originates from dietary exposure. 

PMID- 24448004
TI  - Free-Weight Augmentation With Elastic Bands Improves Bench Press Kinematics in
      Professional Rugby Players.
AB  - Garcia-Lopez, D, Hernandez-Sanchez, S, Martin, E, Marin, PJ, Zarzosa, F, and
      Herrero, AJ. Free-weight augmentation with elastic bands improves bench press
      kinematics in professional rugby players. J Strength Cond Res 30(9): 2493-2499,
      2016-This study aimed to investigate the effects of combining elastic bands to
      free weight resistance (EB + FWR) on the acceleration-deceleration and velocity
      profiles of the bench press in professional rugby players and recreationally
      trained subjects. Sixteen male subjects (8 rugby players and 8 recreationally
      trained subjects) were randomly assigned to complete 2 experimental conditions in
      a crossover fashion: EB + FWR and FWR. In both conditions, subjects performed 1
      bench press set to volitional exhaustion with a load equivalent to the 85% of 1
      repetition maximum (1RM). In the EB + FWR condition, the contribution of elastic
      resistance was approximately 20% of the selected load (85% 1RM). Results indicate
      that EB + FWR condition increased significantly the range of concentric movement
      in which the barbell is accelerated. This increase was significantly higher in
      rugby players (35%) in comparison with recreationally trained subjects (13%).
      Maximal velocity was also increased in EB + FWR (17%), when compared with FWR
      condition. These results suggest that when combined with variable resistance
      (i.e., EB), the external resistance seems to be more evenly distributed over the
      full range of motion, decreasing the need for dramatic deceleration at the end of
      the concentric phase. The present data also indicate that the kinematic benefits
      of an EB + FWR approach seems to be more prominent in athletes from modalities in
      which high level of strength and power are required (i.e., rugby players). 

PMID- 24448003
TI  - Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in
      Eastern James Bay Cree adults.
AB  - There is growing evidence that cardiovascular health can be affected by exposure
      to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1
      (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized
      lipids and protects against cardiovascular diseases. Evidence from in vitro
      studies indicates that MeHg can inhibit PON1 activity but little is known
      regarding this effect in humans. We investigated whether increased blood mercury
      levels are associated with decreased serum PON1 activity in Cree people who are
      exposed to MeHg by fish consumption. We conducted a multi-community study of 881
      Cree adults living in Eastern James Bay communities (Canada). Multivariate
      analyses considered sociodemographic, anthropometric, clinical, dietary and
      lifestyle variables and six PON1 gene variants (rs705379 (-108C/T), rs662
      (Q192R), rs854560 (L55M), rs854572 (-909C/G), rs854571 (-832C/T) and rs705381 (
      162C/T)). In a multiple regression model adjusted for all potential confounding
      factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379
      interaction was observed. Blood mercury levels were inversely associated with
      serum PON1 activities in individual homozygous for the -108T allele (P=0.009).
      Our results suggest a gene-environment interaction between the rs705379
      polymorphism and MeHg exposure on PON1 activity levels in this aboriginal
      population. This finding will need to be replicated in other population studies. 

PMID- 24448005
TI  - High-Intensity Training and Salivary Immunoglobulin A Responses in Professional
      Top-Level Soccer Players: Effect of Training Intensity.
AB  - Owen, AL, Wong, DP, Dunlop, G, Groussard, C, Kebsi, W, Dellal, A, Morgans, R, and
      Zouhal, H. High-intensity training and salivary immunoglobulin A responses in
      professional top-level soccer players: Effect of training intensity. J Strength
      Cond Res 30(9): 2460-2469, 2016-This study aimed (a) to test the hypothesis that
      salivary immunoglobulin A (s-IgA) would vary with training intensity sessions
      (low-intensity [LI] vs. high-intensity sessions [HI]) during a traditional
      training program divided into 4 training periods and (b) to identify key
      variables (e.g., GPS data, rating of perceived exertion [RPE], and training
      duration), which could affect s-IgA. Saliva samples of 10 elite professional
      soccer players were collected (a) before the investigation started to establish
      the baseline level and (b) before and after each 4 training sessions (LI vs. HI).
      Training intensity was monitored as internal (through heart rate responses and
      RPE) and external (through GPS) loads. High-intensity sessions were associated
      with higher external load (GPS) and with higher RPE. Baseline and pretraining s
      IgA did not differ between the 4 training sessions both for HI and LI. Post
      training s-IgA were not different (in absolute value and in percentage of change)
      between HI and LI sessions at the first 3 periods. However, at the fourth period,
      s-IgA concentration for HI session was significantly lower (p <= 0.05) than the
      LI session. The percentage change between s-IgA post-training and s-IgA baseline
      concentrations differ significantly (p <= 0.05) between HI and LI training
      sessions. Significant correlations between s-IgA and training intensity were also
      noted. High-intensity soccer training sessions might cause a significant decrease
      in s-IgA values during the postexercise window as compared with LI sessions. This
      study encourages coaches to monitor s-IgA in routine, particularly during HI
      training periods, to take precautions to avoid upper respiratory tract infection
      in highly trained soccer players. 

PMID- 24448006
TI  - Is the Polar F6 heart rate monitor less accurate during aerobic bench stepping
      because of arm movements?
AB  - Because of the well-documented linear relationship between heart rate and oxygen
      consumption (VO2), heart rate is commonly used to estimate energy expenditure
      during exercise. However, previous research suggests that heart rate increases
      without a concomitant rise in VO2 when arm movements are added to exercise. If
      so, this could impact the accuracy of heart rate monitors in estimating energy
      expenditure during combined arm and leg exercise. This study compared the
      cardiorespiratory responses to a bench step aerobics routine performed with and
      without arm movements and evaluated whether the accuracy of the Polar F6 heart
      rate monitor in predicting energy expenditure was impacted by the inclusion of
      arm movements. Thirty-two women performed the same routine with and without arm
      movements while stepping up and down off of a 15.24-cm bench at a cadence of 128
      b.min-1. Heart rate and VO2 increased, whereas oxygen pulse (VO2.heart rate-1)
      decreased when arm movements were added (p < 0.001). However, the differences
      between the energy expenditure estimated by the Polar F6 heart rate monitor and
      the energy expenditure measured by indirect calorimetry were similar during the
      same aerobic bench stepping routine performed with and without arms (Delta~2
      kCal.min-1, p >= 0.05). Results confirm that arm movements during aerobic bench
      stepping elicit a disproportionate rise in heart rate relative to V[Combining Dot
      Above]O2. However, results do not support that these movements increase the
      prediction error in energy expenditure, as the Polar F6 heart rate monitor over
      predicted energy expenditure when arm movements were involved and when they were
      not involved.

PMID- 24448007
TI  - Timely treatment for acute myocardial infarction and health outcomes: an
      integrative review of the literature.
AB  - BACKGROUND: Coronary heart disease is the most common condition affecting
      Australians. The time sensitive nature of treating ST-segment elevation
      myocardial infarction (STEMI) has been the subject of extensive research for
      several years. Despite important advances in strategies to reduce time to
      treatment, time continues to represent a major determinant of mortality and
      morbidity. Door to balloon time (DTBT) is a key indicator of quality of care for
      STEMI. Nurses play a pivotal role in streamlining the care processes to influence
      timely management of STEMI. PURPOSE: The aim of this paper is to review the
      evidence on the time to treat STEMI, the associated factors impacting upon health
      outcomes and explore systems of care that reduce time to treatment, using an
      integrative review approach. METHOD: Established databases were searched from
      2000 to 2012. The search terms 'myocardial infarction', 'emergency medicine',
      'angioplasty balloon', 'time factors', 'treatment outcome', 'mortality',
      'prognosis', 'female', 'age factors', and 'readmission', were used in various
      combinations. Research studies that addressed the aims of this paper were
      examined. FINDINGS: Twenty-nine papers were included in this integrative review.
      The literature demonstrates a strong relationship between shorter DTBT and
      reduced in-hospital mortality. Factors such as age, gender, time of presentation
      and co-morbid condition were associated with increased in-hospital mortality.
      There is sparse literature examining the effect timely reperfusion has on longer
      term mortality and other longer-term outcomes such as readmission rates and
      occurrence of heart failure. Additionally, strategies that effectively reduced
      DTBT were identified, yet little has been reported on the impact reduced DTBT has
      had upon health outcomes and whether these improvements were sustained.
      CONCLUSION: Whilst the importance of timely reperfusion is now well recognised,
      additional efforts to streamline the process of care and demonstrate sustained
      improvement for STEMI patients is required. Nurses in the areas of emergency
      medicine and cardiac care, play an essential role in facilitating this.

PMID- 24448008
TI  - What is visual ergonomics?

PMID- 24448009
TI  - Good expert knowledge, small scope.
AB  - BACKGROUND: During many years of occupational stress research, mostly within the
      German governmental program for "Humanization of Work Life'', remarkable deficits
      concerning visual work were seen, the most striking being the lack of cooperation
      between the different experts. OBJECTIVE: With regard to this article hard
      arguments and ideas for solutions had to be found. METHODS/PARTICIPANTS: A pilot
      study in 21 enterprises was realized (1602 employees with different visual work
      tasks). A test set of screening parameters (visual acuity, refraction, phoria,
      binocular cooperation and efficiency, accommodation range and color vision) were
      measured. The glasses and/or contact lenses worn were registered and the visual
      tasks analyzed. In work at visual display units (VDU) the eye movements were
      recorded and standardized questionnaires were given (health, stress, visual work
      situation). Because of the heterogeneity of the sample only simple statistics
      were applied: in groups of different visual work the complaints, symptoms,
      hassles and uplifts were clustered (SAS software) and correlated with the results
      of the visual tests. Later a special project in 8 companies (676 employees) was
      carried out. The results were published in [14]. RESULTS: Discomfort and
      asthenopic symptoms could be seen as an interaction of the combination of tasks
      and working conditions with the clusters of individual functionalisms, frequently
      originating in postural compromises. Mainly three causes for stress could be
      identified: 1. demands inadequate with regard to intensity, resolution, amount
      and/or time structure; 2. prevention of elementary perceptive needs; 3. entire
      use of partial capacities of the visual organ. Symptoms also were correlated with
      heteronomy. Other findings: influence of adaptation/accommodation ratio, the
      distracting role of attractors, especially in multitasking jobs; influence of
      high luminance differences. Dry eyes were very common, they could be attributed
      to a high screen position, low light, monotonous tasks and office climate. For
      some parameters a diurnal rhythm could be identified. Nowhere special programs
      for ageing employees were found: the right glasses; retinal problems and signs of
      destabilization of vision. CONCLUSIONS: In all enterprises, the
      ergophthalmological and visual ergonomic knowledge of the occupational physicians
      was poor, visual ergonomists were not available and there was only very poor
      cooperation with ophthalmologists and optometrists, the first of whom
      additionally had not much knowledge of modern work.

PMID- 24448010
TI  - Modification of Fox protocol for prediction of maximum oxygen uptake in male
      university students.
AB  - BACKGROUND: Direct estimation of VO2max involves labourious, exhaustive,
      hazardous, time consuming and expensive experimental protocols. Hence,
      application of various indirect protocols for prediction of VO2max has become
      popular, subject to proper population-specific standardisation of the indirect
      protocol. OBJECTIVES: Application of Fox (1973) protocol in male sedentary
      university students of Kolkata, India led to premature fatigue in their leg
      muscles that hindered the muscular activity leading to inability in completing
      the exercise. The present study was aimed at modifying and validating the Fox
      (1973) protocol with a convenient workload of 110 W (i.e., modified Fox test or
      MFT) in the said population. METHODS: Ninety (90) sedentary male students were
      recruited by simple random sampling from the University of Calcutta, India and
      they were randomly assigned into study group (n=60) and confirmatory group
      (n=30). VO2max was directly estimated by Scholander micro-gas analysis after
      incremental bicycle exercise. Predicted VO2max (PVO2max) was computed from MFT by
      using the submaximal heart rate (HR(sub). RESULTS: In the Study Group VO2max
      (2216.63 +/- 316.77 mL.min-1 was significantly different (P< 0.001) from PVO2max
      (3131.73 +/- 234.32 mL.min-1 measured by using the equation of Fox (1973). Simple
      and multiple regression equations have been computed for prediction of VO2max
      from HR(sub) and physical parameters. Application of these norms in the
      confirmatory group depicted insignificant difference between VO2max and PVO2max
      with substantially small limits of agreement and lower values of SEE. CONCLUSION:
      The modified regression norms are therefore recommended for use in MFT for
      accurate assessment of VO2max in the studied population.

PMID- 24448011
TI  - The compensatory motion of wrist immobilization on thumb and index finger
      performance--kinematic analysis and clinical implications.
AB  - BACKGROUND: Based on the high prevalence of people with problems in the wrist and
      hand simultaneously, it is of its importance to clarify whether hand joints exert
      extra motion to compensate for wrist motion while immobilized. OBJECTIVE: This
      study aimed to measure the compensatory movement of the thumb and index finger
      when people perform daily activities with an immobilized wrist. METHODS: Thirty
      healthy volunteers were recruited in this study. A wrist splint, the Jebsen
      Taylor Hand Function Test, and the OptoTrak Certus motion tracking system were
      used. Seven inter-digit mean joint angles of the index finger and thumb were
      calculated. Paired sample t-test was used. RESULTS: (1) The compensatory motions
      were noted in the Metacarpophalangeal and Carpometacarpal joints of the thumb,
      and the proximal interphalangeal joints of the index finger; (2) The
      manifestation of compensatory motion was related to type of activity performed
      except when picking up light and heavy cans. CONCLUSIONS: The compensatory
      motions appeared while the wrist was immobilized and were found to be
      disadvantageous to the progression of disease. In the future, studies need to be
      done to understand how to select products with correct ergonomic design to enable
      people to reap greater benefits from wearing wrist splints.

PMID- 24448012
TI  - Patient manual handling risk assessment among hospital nurses.
AB  - BACKGROUND: Manual patient handling is known to be the major source of
      musculoskeletal load among hospital nurses. OBJECTIVES: The objectives of this
      study were to determine prevalence of musculoskeletal disorders (MSDs), assess
      patient manual handling risk and identify major factors associated with MSDs
      symptoms among hospital nursing staff. METHODS: This cross-sectional study was
      conducted among 400 randomly selected nurses from 75 wards of 11 hospitals. Data
      were collected by demographic and Nordic musculoskeletal questionnaires together
      with MAPO checklist. Prevalence of MSDs was estimated with confidence interval of
      95%. Chi-square test and independent sample t-test were used to investigate
      differences of MSDs prevalence for demographic variables between the subjects
      with and without MSDs. Multiple logistic regression analysis was performed
      (forward: Wald) to determine MSDs associated risk factors. RESULTS: The means of
      age and job tenure in subjects were 30.76 +/- 6.44 and 6.92 +/- 5.75 years,
      respectively. Some form of musculoskeletal symptoms had been experienced during
      the last 12 months by 88.2% of the subjects. MAPO assessment revealed that 83.5%
      of the individuals were at risk. Statistical analysis showed that job tenure,
      nurse to bed ratio, gender, shift working and MAPO score were associated with
      MSDs (p< 0.05). CONCLUSIONS: Prevalence of MSDs in hospital nursing personnel was
      high and the occurrence of MSDs was found to be associated with MAPO score. Based
      on the results, to improve working conditions, it is imperative to provide
      lifting equipment, implement training programs and increase nurse to bed ratio in
      hospitals.

PMID- 24448013
TI  - Working spectacles for sorting mail.
AB  - BACKGROUND: Sorting mail into racks for postmen is visually demanding work. This
      can result in backward inclination of their heads, especially more pronounced for
      those who use progressive addition lenses. OBJECTIVE: To evaluate the effects of
      customized working spectacles on the physical workload of postmen. METHODS:
      Twelve male postmen sorted mail on two occasions: once using their private
      progressive spectacles and once using customized sorting spectacles with inverted
      progressive lenses. Postures and movements of the head, upper back, neck, and
      upper arms were measured by inclinometry. The muscular load of the trapezius was
      measured by surface electromyography. RESULTS: With the customized sorting
      spectacles, both the backward inclination of the head and backward flexion of the
      neck were reduced (3 degrees ), as well as the muscular load of the right upper
      trapezius, compared to sorting with private spectacles. However, with the sorting
      spectacles, there was a tendency for increased neck forward flexion, and
      increased sorting time. CONCLUSION: The reduction in work load may reduce the
      risk for developing work-related musculoskeletal disorders due to the positive
      reduction of the backward inclination of the head. But the tendency for increased
      neck forward flexion may reduce the positive effects. However, the magnitude of
      the possible reduction is difficult to predict, especially since quantitative
      data on exposure-response relationships are unknown. Alternative working
      spectacles with inverted near progressive lenses ought to be evaluated. They
      should still result in a positive reduced backward inclination of the head and
      may not cause any increased forward flexion.

PMID- 24448014
TI  - Strong support for relocation to other work tasks: A cross-sectional study of
      attitudes to sickness insurance regulations in Sweden.
AB  - BACKGROUND: Profound changes are taking place in the Swedish welfare state. The
      general population's attitudes are important insofar changes will be perceived as
      fair and effective to become implemented. OBJECTIVE: The aim was to study
      attitudes to the strictness of the sick-leave rules, relocation to other work
      tasks after 3 months of sick leave and applications for new jobs after 6 months
      of sick leave. METHODS: Eligible for this questionnaire study were 1,140
      individuals aged 19 to 64 years. Their attitudes were analyzed in relation to
      age, gender, political ideology and health status. Health status was measured as
      sick-leave experiences, self-reported health and level of symptoms. RESULTS:
      Showed that 42% considered the sick-leave rules to be too strict, 60% found
      relocation to other work tasks to be good while 35% found that applications for
      new work were good. In logistic regression analyses, high sick-leave experience
      was associated with increased odds of finding the sick-leave rules too strict and
      disagreement with relocation to other work tasks or application for new jobs.
      CONCLUSIONS: In conclusion, strong support was found for relocation to other work
      tasks with the present employer. Earlier research on returning to work has found
      workplace interventions to be efficient. From a policy perspective it seems
      relevant to promote such interventions given the strong public opinion in their
      favor.

PMID- 24448015
TI  - Access improvement to aircraft passengers' hand luggage.
AB  - BACKGROUND: Efficient use of space and passenger comfort in aircraft interiors
      are major issues. There is not much research available about the flying
      experience regarding passengers' personal belongings. OBJECTIVE: The objective of
      this study is to explore concepts within the current aircraft seats which improve
      the passenger experience related to their personal belongings like wallets,
      mobile phones and laptops. METHODS: Through on-site observations, interviews and
      online questionnaires, data regarding the number of personal belongings taken
      into the airplane and opinions about access to hand luggage were gathered. These
      data were used to develop different concepts to optimize the aircraft interior,
      which were evaluated by passengers. RESULTS: Almost every passenger carries a
      phone (88%), wallet (94%), travel documents (98%) and keys (76%) with them and
      they like to have these stored close by. Passengers rate the concept that
      provides integrated storage in the tray table of the aircraft seat the best.
      CONCLUSIONS: Extra storage possibility in the table-tray seems a promising
      solution according to the passengers.

PMID- 24448016
TI  - Social cognition and work performance of persons with schizophrenia in a Chinese
      population.
AB  - BACKGROUND: Social-cognitive deficits have a significant impact on the community
      and vocational functioning of persons with schizophrenia. OBJECTIVE: This study
      aimed to explore the relationship between social-cognitive abilities and
      vocational functioning in a Chinese population. METHOD: We recruited 30
      outpatients with schizophrenia to participate. We administered the Chinese Social
      Cognition and Screening Questionnaire (C-SCSQ) to assess Theory of Mind (ToM),
      attributional bias, and neurocognition; the Facial Expression Identification Test
      (FEIT) to assess emotion perception (EP) ability, and the Chinese Work
      Personality Profile (CWPP) to assess work performance in a simulated work
      setting. RESULTS: ToM showed a significant negative correlation with
      attributional bias. The neurocognitive measure displayed a significant positive
      correlation with ToM and EP. The structural equation model was a good fit to the
      data (CFI=0.91, RMSEA=0.12), and showed that social-cognitive abilities had a
      significant impact (-0.41) on work performance. Of the four social-cognitive
      domains, ToM and paranoid attributional style (PAS) contributed significantly to
      variations in work performance. These results support the theory that social
      cognitive abilities have an impact on work performance. ToM has a positive impact
      whereas PAS has an adverse effect. CONCLUSION: Persons with schizophrenia present
      specific deficits in their social-cognitive abilities, which have significant
      impact on their work performance and employability.

PMID- 24448017
TI  - Worksite back and core exercise in firefighters: Effect on development of lumbar
      multifidus muscle size.
AB  - BACKGROUND: Firefighting is a dangerous occupation with a high incidence of low
      back pain and injury. Abnormal back muscle function and morphology has been
      linked to low back pain and poor physical performance. The effect of exercise
      training on back muscle size and symmetry has not been investigated in
      firefighters. OBJECTIVE: The purpose of this study was to assess the effect of
      worksite exercise training for eliciting lumbar multifidus muscle hypertrophy in
      firefighters. METHODS: A cluster randomized controlled trial was conducted with
      healthy, career firefighters (n=64) from a medium-sized fire department.
      Participants were randomized by fire station to exercise training (n=36)
      (supervised back and core exercise performed on duty, 2X/week, 24 weeks) or
      control (n=28). The cross-sectional area (CSA) of the L4 and L5 lumbar multifidus
      muscle was assessed with ultrasonography at baseline and following the
      intervention. RESULTS: At 24 weeks, no significant differences were noted between
      the groups in the adjusted (by baseline scores and body mass) L4 and L5 lumbar
      multifidus muscle CSA and asymmetry values. CONCLUSIONS: A worksite exercise
      training program targeting the back and core is not effective for eliciting
      hypertrophy of the lumbar multifidus muscle in healthy firefighters.

PMID- 24448018
TI  - Perceived floor slipperiness and floor roughness in a gait experiment.
AB  - BACKGROUND: Slips and falls contribute to occupational injuries and fatalities
      globally. Both floor slipperiness and floor roughness affect the occurrence of
      slipping and falling. Investigations on fall-related phenomena are important for
      the safety and health of workers. OBJECTIVE: The purposes of this study were to:
      compare the perceived floor slipperiness before and after walking on the floor;
      compare the perceived floor slipperiness with and without shoes for males and
      females; discuss the perceived floor roughness based on barefoot walking; and
      establish regression models to describe the relationship between perceived floor
      slipperiness and actual friction of the floors. METHODS: Male and female subjects
      walked on 3 m walkways with or without shoes. The perceived floor slipperiness
      ratings both before and after their walk were collected. RESULTS: The perceived
      floor slipperiness both before and after walking were significantly affected by
      both floor and surface conditions. Gender, floor, surface, and footwear
      conditions were all significant factors affecting the adjustment of perceived
      floor slipperiness. The subjects made more adjustment on perceived floor
      slipperiness rating when they had shoes on than when they were barefooted.
      CONCLUSION: Regression models were established to describe the relationship
      between perceived floor slipperiness and floor coefficient of friction. These
      models may be used to estimate perceived floor slipperiness, or in reverse, the
      coefficient of friction of the floor, so as to prevent slipping and falling in
      workplaces.

PMID- 24448019
TI  - Primary high-grade salivary-type duct carcinoma of the lung: a case report.
AB  - Primary salivary gland-type lung cancers are a rare group of tumors. When they do
      occur, the most common type is adenoid cystic carcinoma, followed by
      mucoepidermoid carcinoma. Primary high-grade salivary-type duct carcinoma (HGSDC)
      arising in the lung has not been described. We report a case of primary pulmonary
      HGSDC in a 55-year-old woman who was referred to our hospital for a suspicious
      lung tumor. The chest computed tomography revealed a solid mass in the left upper
      lobe. A lobectomy was performed afterward, and the mass was a primary lung HGSDC.
      To the best of our knowledge, HGSDC arising in the lung has not been reported
      previously. 

PMID- 24448020
TI  - Mechanistic vs. Empirical network models of drug action.
AB  - Declining success rates coupled with increased costs is leading to an inevitable
      breaking point in the drug development pipeline. Can we avoid it by incorporating
      the vast mechanistic understanding of drug action? A recent review highlights
      this dilemma and proposes "quantitative logic gate" modeling as a solution.(1)
      The goal of this commentary is to contrast this approach with mechanistic
      biochemical network models, which, although alluded to by Kiruoac and Onsum,
      requires a closer analysis. 

PMID- 24448021
TI  - Integration of in vitro binding mechanism into the semiphysiologically based
      pharmacokinetic interaction model between ketoconazole and midazolam.
AB  - In vitro screening for drug-drug interactions is an integral component of drug
      development, with larger emphasis now placed on the use of in vitro parameters to
      predict clinical inhibition. However, large variability exists in Ki reported for
      ketoconazole with midazolam, a model inhibitor-substrate pair for CYP3A. We
      reviewed the literature and extracted Ki for ketoconazole as measured by the
      inhibition of hydroxymidazolam formation in human liver microsomes. The superset
      of data collected was analyzed for the impact of microsomal binding, using
      Langmuir and phase equilibrium binding models, and fitted to various inhibition
      models: competitive, noncompetitive, and mixed. A mixed inhibition model with
      binding corrected by an independent binding model was best able to fit the data
      (Kic = 19.2 nmol/l and Kin = 39.8 nmol/l) and to predict clinical effect of
      ketoconazole on midazolam area under the concentration-time curve. The
      variability of reported Ki may partially be explained by microsomal binding and
      choice of inhibition model. 

PMID- 24448022
TI  - Medication-wide association studies.
AB  - Undiscovered side effects of drugs can have a profound effect on the health of
      the nation, and electronic health-care databases offer opportunities to speed up
      the discovery of these side effects. We applied a "medication-wide association
      study" approach that combined multivariate analysis with exploratory
      visualization to study four health outcomes of interest in an administrative
      claims database of 46 million patients and a clinical database of 11 million
      patients. The technique had good predictive value, but there was no threshold
      high enough to eliminate false-positive findings. The visualization not only
      highlighted the class effects that strengthened the review of specific products
      but also underscored the challenges in confounding. These findings suggest that
      observational databases are useful for identifying potential associations that
      warrant further consideration but are unlikely to provide definitive evidence of
      causal effects. 

PMID- 24448023
TI  - MiR-144 regulates hematopoiesis and vascular development by targeting meis1
      during zebrafish development.
AB  - Hematopoiesis is a dynamic process by which peripheral blood lineages are
      developed. It is a process tightly regulated by many intrinsic and extrinsic
      factors, including transcriptional factors and signaling molecules. However, the
      epigenetic regulation of hematopoiesis, for example, regulation via microRNAs
      (miRNAs), remains incompletely understood. Here we show that miR-144 regulates
      hematopoiesis and vascular development in zebrafish. Overexpression of miR-144
      inhibited primitive hematopoiesis as demonstrated by a reduced number of
      circulating blood cells, reduced o-dianisidine staining of hemoglobin, and
      reduced expression of hbalphae1, hbbetae1, gata1 and pu.1. Overexpression of miR
      144 also inhibited definitive hematopoiesis as shown by reduced expression of
      runx1 and c-myb. Mechanistically, miR-144 regulates hematopoiesis by repressing
      expression of meis1 involved in hematopoiesis. Both real-time RT-PCR and Western
      blot analyses showed that overexpression of miR-144 repressed expression of
      meis1. Bioinformatic analysis predicts a target binding sequence for miR-144 at
      the 3'-UTR of meis1. Deletion of the miR-144 target sequence eliminated the
      repression of meis1 expression mediated by miR-144. The miR-144-mediated abnormal
      phenotypes were partially rescued by co-injection of meis1 mRNA and could be
      almost completely rescued by injection of both meis1 and gata1 mRNA. Finally,
      because meis1 is involved in vascular development, we tested the effect of miR
      144 on vascular development. Overexpression of miR-144 resulted in abnormal
      vascular development of intersegmental vessels in transgenic zebrafish with Flk1p
      EGFP, and the defect was rescued by co-injection of meis1 mRNA. These findings
      establish miR-144 as a novel miRNA that regulates hematopoiesis and vascular
      development by repressing expression of meis1. 

PMID- 24448024
TI  - microRNA-146 up-regulation predicts the prognosis of non-small cell lung cancer
      by miRNA in situ hybridization.
AB  - Non-small cell lung cancer (NSCLC) accounts for approximately 70% of all lung
      cancer-related deaths worldwide. Prognostic markers are essential for the early
      detection of lung cancer in patients. In this study, we first identified
      microRNA146 (miR-146) expression in cancer cell lines using miRNA in situ
      hybridization (MISH) and confirmed the accuracy of MISH using q-RT-PCR. In
      addition, two different systems, BCIP/NBT and ELF, were used to detect the signal
      for a comparative analysis of the specificity of MISH. Compared to the BCIP/NBT
      system, the ELF detection system was more effective for MISH. Furthermore we
      detected the expression of miR-146 in NSCLC tissues (43 cases) and normal tissues
      (32 cases). Based on our results, we can conclude that miR-146 is more highly
      expressed in cancer tissue than normal tissue (t-test, P<0.05) and that miR-146
      can predict the prognosis of NSCLC by MISH. Our findings preliminary demonstrate
      that MISH can be applied as a molecular diagnostic tool to determine the
      expression and localization of miRNAs in cancer tissues and that miR-146,
      determined by MISH, predicts the prognosis of NSCLC patients. 

PMID- 24448025
TI  - Cyanobacterial fossils from 252 Ma old microbialites and their environmental
      significance.
AB  - The end-Permian mass extinction was followed by the formation of an enigmatic
      rock layer with a distinctive macroscopic spotted or dendroid fabric. This
      deposit has been interpreted as microbial reef rock, digitate dendrolite, digital
      thrombolite, dendritic thrombolite, or bacterial deposits. Agreement has been
      reached in considering them as microbialites, but not in their formation. This
      study has revealed that the spotted and dendroid microbialites were composed of
      numerous fossil casts formed by the planktic cyanobacterium, Microcystis, a
      coccoid genus that at the present-day commonly forms blooms in modern lakes,
      rivers, and reservoirs. The abundance of the fossils and the diagenesis they
      experienced has determined the macroscopic fabric: where they abundant, the rock
      appears as dendroid, otherwise, it appears as spotted. The ancient Microcystis
      bloom might produce toxin to kill other metazoans, and be responsible for the
      oceanic anoxia that has puzzled so many researchers for so many years. 

PMID- 24448026
TI  - Nano-sized heterometallic macrocycles based on 4-pyridinylboron-capped iron(II)
      clathrochelates: syntheses, structures and properties.
AB  - Ir-Fe heterometallic macrocycles from clathrochelate-based bipyridyl and
      bis(amidinate) ligands with controllable cavity size have been prepared and
      characterized. 

PMID- 24448027
TI  - Towards a better understanding of people's responses to renewable energy
      technologies: Insights from Social Representations Theory.
AB  - In the past few years, social research has been examining what contributes to the
      attitude-behaviour gap in people's responses to large-scale renewable energy
      technologies. The NIMBY explanation for the gap has long dominated that area of
      research, but has also been criticised. Alternative proposals to NIMBY were
      advanced, but it is still evident that some of those maintain presuppositions of
      NIMBY and that this area of research needs more integration, namely at a
      theoretical level. In this paper we argue that to overcome those aspects it is
      relevant, first, to situate the promotion of renewable energy production as a
      social change process in today's societies, and, second, to therefore consider
      the socio-psychological aspects involved in people's responses to social change.
      We discuss specifically how the Theory of Social Representations may help us with
      that and contribute to a better understanding of people's responses to renewable
      energy technologies. 

PMID- 24448028
TI  - Mid- to long-term results of total lumbar disc replacement: a prospective
      analysis with 5- to 10-year follow-up.
AB  - BACKGROUND CONTEXT: The role of fusion of lumbar motion segments for the
      treatment of intractable low back pain (LBP) from degenerative disc disease (DDD)
      without deformities or instabilities remains controversially debated. Total
      lumbar disc replacement (TDR) has been used as an alternative in a highly
      selected patient cohort. However, the amount of long-term follow-up (FU) data on
      TDR is limited. In the United States, insurers have refused to reimburse surgeons
      for TDRs for fear of delayed complications, revisions, and unknown secondary
      costs, leading to a drastic decline in TDR numbers. PURPOSE: To assess the mid-
      and long-term clinical efficacy as well as patient safety of TDR in terms of
      perioperative complication and reoperation rates. STUDY DESIGN/SETTING:
      Prospective, single-center clinical investigation of TDR with ProDisc II
      (Synthes, Paoli, PA, USA) for the treatment of LBP from lumbar DDD that has
      proven unresponsive to conservative therapy. PATIENT SAMPLE: Patients with a
      minimum of 5-year FU after TDR, performed for the treatment of intractable and
      predominant (>=80%) axial LBP resulting from DDD without any deformities or
      instabilities. OUTCOME MEASURES: Visual analog scale (VAS), Oswestry Disability
      Index (ODI), and patient satisfaction rates (three-scale outcome rating);
      complication and reoperation rates as well as elapsed time until revision
      surgery; patient's professional activity/employment status. METHODS: Clinical
      outcome scores were acquired within the framework of an ongoing prospective
      clinical trial. Patients were examined preoperatively, 3, 6, and 12 months
      postoperatively, annually from then onward. The data acquisition was performed by
      members of the clinic's spine unit including medical staff, research assistants,
      and research nurses who were not involved in the process of pre- or postoperative
      decision-making. RESULTS: The initial cohort consisted of 201 patients; 181
      patients were available for final FU, resembling a 90.0% FU rate after a mean FU
      of 7.4 years (range 5.0-10.8 years). The overall results revealed a highly
      significant improvement from baseline VAS and ODI levels at all postoperative FU
      stages (p<.0001). VAS scores demonstrated a slight (from VAS 2.6 to 3.3) but
      statistically significant deterioration from 48 months onward (p<.05). Patient
      satisfaction rates remained stable throughout the entire postoperative course,
      with 63.6% of patients reporting a highly satisfactory or a satisfactory (22.7%)
      outcome, whereas 13.7% of patients were not satisfied. The overall complication
      rate was 14.4% (N=26/181). The incidence of revision surgeries for general and/or
      device-related complications was 7.2% (N=13/181). Two-level TDRs demonstrated a
      significant improvement of VAS and ODI scores in comparison to baseline levels
      (p<.05). Nevertheless, the results were significantly inferior in comparison to
      one-level cases and were associated with higher complication (11.9% vs. 27.6%;
      p=.03) and inferior satisfaction rates (p<.003). CONCLUSIONS: Despite the fact
      that the current data comprises the early experiences and learning curve
      associated with a new surgical technique, the results demonstrate satisfactory
      and maintained mid- to long-term clinical results after a mean FU of 7.4 years.
      Patient safety was proven with acceptable complication and reoperation rates.
      Fear of excessive late complications or reoperations following the primary TDR
      procedure cannot be substantiated with the present data. In carefully selected
      cases, TDR can be considered a viable treatment alternative to lumbar fusion for
      which spine communities around the world seem to have accepted mediocre clinical
      results as well as obvious and significant drawbacks.

PMID- 24448029
TI  - Efficient removal of antibiotics in surface-flow constructed wetlands, with no
      observed impact on antibiotic resistance genes.
AB  - Recently, there have been growing concerns about pharmaceuticals including
      antibiotics as environmental contaminants. Antibiotics of concentrations commonly
      encountered in wastewater have been suggested to affect bacterial population
      dynamics and to promote dissemination of antibiotic resistance. Conventional
      wastewater treatment processes do not always adequately remove pharmaceuticals
      causing environmental dissemination of low levels of these compounds. Using
      constructed wetlands as an additional treatment step after sewage treatment
      plants have been proposed as a cheap alternative to increase reduction of
      wastewater contaminants, however this means that the natural microbial community
      of the wetlands becomes exposed to elevated levels of antibiotics. In this study,
      experimental surface-flow wetlands in Sweden were continuously exposed to
      antibiotics of concentrations commonly encountered in wastewater. The aim was to
      assess the antibiotic removal efficiency of constructed wetlands and to evaluate
      the impact of low levels of antibiotics on bacterial diversity, resistance
      development and expression in the wetland bacterial community. Antibiotic
      concentrations were measured using liquid chromatography-mass spectrometry and
      the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing
      gradient gel electrophoresis. Real-time PCR was used to detect and quantify
      antibiotic resistance genes and integrons in the wetlands, during and after the
      exposure period. The results indicated that the antibiotic removal efficiency of
      constructed wetlands was comparable to conventional wastewater treatment schemes.
      Furthermore, short-term treatment of the constructed wetlands with
      environmentally relevant concentrations (i.e. 100-2000 ng*l(-1)) of antibiotics
      did not significantly affect resistance gene concentrations, suggesting that
      surface-flow constructed wetlands are well-suited for wastewater treatment
      purposes.

PMID- 24448030
TI  - Assessment of natural background levels in potentially contaminated coastal
      aquifers.
AB  - The estimation of natural background levels (NBLs) of dissolved concentrations of
      target chemical species in subsurface reservoirs relies on a proper assessment of
      the effects of forcing terms driving flow and transport processes taking place
      within the system and whose dynamics drive background concentration values. We
      propose coupling methodologies based on (a) global statistical analyses and (b)
      numerical modeling of system dynamics to distinguish between the impacts of
      different types of external forcing components influencing background
      concentration values. We focus on the joint application of a statistical
      methodology based on Component Separation and experimental/numerical modeling
      studies of groundwater flow and transport for the NBL estimation of selected
      chemical species in potentially contaminated coastal aquifers. We consider a site
      which is located in Calabria, Italy, and constitutes a typical example of a
      Mediterranean coastal aquifer which has been subject to intense industrial
      development. Our study is keyed to the characterization of NBLs of manganese and
      sulfate and is geared to the proper identification of the importance of a natural
      external forcing (i.e., seawater intrusion) on NBL assessment. Results from the
      Component Separation statistical approach are complemented by numerical
      simulations of the advective-dispersive processes that could influence the
      distribution of chemical species (i.e., sulfate) within the system. Estimated
      NBLs for manganese are consistent with the geochemical composition of soil
      samples. While Component Separation ascribes the largest detected sulfate
      concentrations to anthropogenic sources, our numerical modeling analysis suggests
      that they are mainly related to the natural process of seawater intrusion. Our
      results indicate that the use of statistical methodologies in complex groundwater
      systems should be assisted by a detailed characterization of the dynamics of
      natural (and/or induced) processes to distinguish effective anthropogenic
      contamination from natural conditions and to define realistic environmental clean
      up goals. 

PMID- 24448031
TI  - De novo epidermal regeneration using human eccrine sweat gland cells: higher
      competence of secretory over absorptive cells.
AB  - In our previous work, we showed that human sweat gland-derived epithelial cells
      represent an alternative source of keratinocytes to grow a near normal autologous
      epidermis. The role of subtypes of sweat gland cells in epidermal regeneration
      and maintenance remained unclear. In this study, we compare the regenerative
      potential of both secretory and absorptive sweat gland cell subpopulations. We
      demonstrate the superiority of secretory over absorptive cells in forming a new
      epidermis on two levels: first, the proliferative and colony-forming efficiencies
      in vitro are significantly higher for secretory cells (SCs), and second, SCs show
      a higher frequency of successful epidermis formation as well as an increase in
      the thickness of the formed epidermis in the in vitro and in vivo functional
      analyses using a 3D dermo-epidermal skin model. However, the ability of forming
      functional skin substitutes is not limited to SCs, which supports the hypothesis
      that multiple subtypes of sweat gland epithelial cells hold regenerative
      properties, while the existence and exact localization of a keratinocyte stem
      cell population in the human eccrine sweat gland remain elusive. 

PMID- 24448033
TI  - Creation of a novel, interdisciplinary, multisite clerkship: "understanding
      lupus".
AB  - Few medical school electives include longitudinal patient care across clinical
      specialties and environments. Systemic lupus erythematosus represents a disease
      process with complex pathophysiology for students to learn from providers across
      medical fields, including dermatology, rheumatology, nephrology, and cardiology,
      in both pediatric and adult patients. Diagnosis, understanding, and management of
      lupus also rely heavily on basic science and clinical immunology, providing a
      link to the preclinical curriculum. In 2009, Harvard Medical School introduced a
      one-month elective course "Understanding Lupus: A Multidisciplinary Approach to
      Systemic Disease," designed to provide students with both outpatient and
      inpatient care experiences in dermatology, rheumatology, and multidisciplinary
      clinics at Brigham and Women's Hospital and Boston Children's Hospital. Core
      components of the elective include a continuity experience that allows students
      to attend one patient's multiple specialist visits; didactics from dermatology,
      rheumatology, and immunology covering evidence-based medicine and basic sciences;
      and clinical immunology laboratory exposure to teach serologic and auto-antibody
      testing methods. The authors provide lessons learned in the development of this
      interdisciplinary, multi-institution elective rotation, which may serve as a
      model at other medical schools for incorporating basic sciences into the clinical
      curriculum and using multidisciplinary care and varied educational settings. 

PMID- 24448032
TI  - Psychological stress with long-standing allergic dermatitis causes
      psychodermatological conditions in mice.
AB  - Psychological factors have long been assumed to be involved in the pathogenesis
      of allergic skin diseases. The effects of psychological stress on allergic
      contact dermatitis (ACD) have been experimentally well investigated; however, the
      effects of ACD on stress responses are largely unknown. Here, we report that
      preceding chronic ACD dramatically affects the behavioral and physiological
      stress responses to social isolation (a psychological stressor). In male BALB/c
      mice, social isolation combined with long-standing (>2 months) ACD by repeated
      hapten application caused characteristic symptoms, including chronic dermatitis
      from persistent self-scratching, behavioral changes related to fear/anxiety, and
      elevated serum IgE levels. The symptoms were maintained by social isolation alone
      without further hapten application after the onset, and were improved by
      resocialization. Treatment with topical corticosteroids exacerbated chronic
      scratch dermatitis, whereas it was effective for chronic ACD. These results show
      that the symptoms represent a de novo development of a specific disease state and
      not a mere exacerbation of a preexisting allergic inflammation. With this
      experimental protocol, similar results were obtained in several other strains of
      mice. This murine model provides a tool for investigating the pathogenesis and
      treatment of allergic skin disease with psychodermatological aspects. 

PMID- 24448034
TI  - A transparent oversight policy for human anatomical specimen management: the
      University of California, Davis experience.
AB  - The authors describe the development and implementation of a University of
      California (UC) system of oversight, education, tracking, and accountability for
      human anatomical specimen use in education and research activities. This program
      was created and initially implemented at UC Davis in 2005. Several incidents
      arising out of the handling of human anatomical specimens at UC campuses revealed
      significant challenges in the system for maintaining control of human anatomical
      specimens used in education and research. These events combined to undermine the
      public perception for research and educational endeavors involving anatomical
      materials at public institutions. Risks associated with the acquisition,
      maintenance, and disposal of these specimens were not fully understood by the
      faculty, staff, and students who used them. Laws governing sources of specimens
      are grouped with those that govern organ procurement and tissue banking, and
      sometimes are found in cemetery and funeral regulations. These variables
      complicate interpretations and may hinder compliance. To regain confidence in the
      system, the need to set appropriate and realistic guidelines that mitigate risk
      and facilitate an institution's research and educational mission was identified.
      This article chronicles a multiyear process in which diverse stakeholders
      developed (1) a regulatory policy for oversight, (2) a policy education program,
      (3) procedures for tracking and accountability, and (4) a reporting and
      enforcement mechanism for appropriate and ethical use of human anatomical
      specimens in university education and research. 

PMID- 24448035
TI  - Simulated electronic health record (Sim-EHR) curriculum: teaching EHR skills and
      use of the EHR for disease management and prevention.
AB  - Electronic health records (EHRs) can improve many aspects of patient care, yet
      few formal EHR curricula exist to teach optimal use to students and other
      trainees. The Simulated EHR (Sim-EHR) curriculum was introduced in January 2011
      at Oregon Health & Science University (OHSU) to provide learners with a safe
      hands-on environment in which to apply evidence-based guidelines while learning
      EHR skills. Using an EHR training platform identical to the OHSU EHR system,
      learners review and correct a simulated medical chart for a complex virtual
      patient with chronic diseases and years of fragmented care. They write orders and
      prescriptions, create an evidence-based plan of care for indicated disease
      prevention and management, and review their work in a small-group setting. Third
      year students complete the Sim-EHR curriculum as part of the required family
      medicine clerkship; their chart work is assessed using a rubric tied to the
      curriculum's general and specific objectives. As of January 2014, 406 third-year
      OHSU medical students, on campus or at remote clerkship sites, and 21 OHSU
      internal medicine interns had completed simulated charts.In this article, the
      authors describe the development and implementation of the Sim-EHR curriculum,
      with a focus on use of the curriculum in the family medicine clerkship. They also
      share preliminary findings and lessons learned. They suggest that the Sim-EHR
      curriculum is an effective, interactive method for providing learners with EHR
      skills education while demonstrating how a well-organized chart helps ensure
      safe, efficient, and quality patient care. 

PMID- 24448036
TI  - Weekly and consecutive day neonatal intubation training: comparable on a
      pediatrics clerkship.
AB  - PURPOSE: To determine whether medical student intubation proficiency with a
      neonatal mannequin differs according to weekly or consecutive day practice
      sessions during a six-week pediatric clerkship. METHOD: From July 2010 through
      June 2011, the authors prospectively randomized 110 third-year medical students
      into three neonatal intubation practice groups: standard (control; no practice
      sessions), weekly (practice once/week for four consecutive weeks), or consecutive
      day (practice once/day for four consecutive days). At baseline, students
      performed intubation during individual sessions using a neonatal mannequin
      (SimNewB). Two reviewers, blinded to practice group, viewed videotapes of
      intubations and independently scored students on equipment selection, procedural
      skill steps, length of intubation attempts (in seconds), and the number of
      attempts (up to three) needed for a successful intubation. Videotaped individual
      final assessment intubation sessions during week six were evaluated in the same
      manner. RESULTS: Students in the weekly and consecutive day practice groups
      performed better at the final assessment on all variables than students in the
      standard group (P < .001), but over six weeks, the authors detected no
      differences between the two distributed practice formats for any outcomes of
      interest. CONCLUSIONS: Practice improved all aspects of neonatal intubation
      performance, including choosing the correct equipment, properly performing the
      skill steps, length of time to successful intubation, and success rate, for
      novice health care providers in a simulation setting. Over six weeks, neither
      practice format proved superior, but it remains unclear whether one format is
      superior for learning and skill retention over the long term or in actual
      practice.

PMID- 24448037
TI  - Rethinking the discharge summary: a focus on handoff communication.
AB  - The discharge summary is one of the most critical documents in medical care
      settings, but it is prone to systematic lapses that compromise the continuity of
      care. Discontinuity is fostered not only by incomplete inclusion of data (such as
      pending labs or medication reconciliations) but also by failure to document
      clinical reasoning and unfinished diagnostic workups. To correct these problems,
      the authors propose the Situation-Background-Assessment-Recommendations (SBAR)
      format for discharge summaries. SBAR is already used for handoffs the way
      Subjective-Objective-Assessment-Plan is for progress notes. The SBAR format
      supports the concise presentation of relevant information along with guidance for
      action. It shifts the paradigm and purpose of the discharge summary away from
      being a "Captain's Log" (a historical record of the events, actions taken, and
      their consequences during hospitalization) and towards being a handoff document
      (a tool for communication between health professionals aimed at ensuring
      continuity of care). To test SBAR as a template for discharge summaries, the
      authors have initiated a study to document the impact of the SBAR model on the
      quality of trainees' thinking in discharge summaries. 

PMID- 24448038
TI  - Reconsidering fidelity in simulation-based training.
AB  - In simulation-based health professions education, the concept of simulator
      fidelity is usually understood as the degree to which a simulator looks, feels,
      and acts like a human patient. Although this can be a useful guide in designing
      simulators, this definition emphasizes technological advances and physical
      resemblance over principles of educational effectiveness. In fact, several
      empirical studies have shown that the degree of fidelity appears to be
      independent of educational effectiveness. The authors confronted these issues
      while conducting a recent systematic review of simulation-based health
      professions education, and in this Perspective they use their experience in
      conducting that review to examine key concepts and assumptions surrounding the
      topic of fidelity in simulation.Several concepts typically associated with
      fidelity are more useful in explaining educational effectiveness, such as
      transfer of learning, learner engagement, and suspension of disbelief. Given that
      these concepts more directly influence properties of the learning experience, the
      authors make the following recommendations: (1) abandon the term fidelity in
      simulation-based health professions education and replace it with terms
      reflecting the underlying primary concepts of physical resemblance and functional
      task alignment; (2) make a shift away from the current emphasis on physical
      resemblance to a focus on functional correspondence between the simulator and the
      applied context; and (3) focus on methods to enhance educational effectiveness
      using principles of transfer of learning, learner engagement, and suspension of
      disbelief. These recommendations clarify underlying concepts for researchers in
      simulation-based health professions education and will help advance this
      burgeoning field. 

PMID- 24448039
TI  - The nursing home as a learning environment: dealing with less is learning more.
AB  - PURPOSE: Despite the imperative to develop adequate competence in caring for the
      growing demographic of elderly patients with complex health care problems,
      nursing homes are underused as learning environments for the education of future
      doctors; thus, the authors aimed to gain more insight into the characteristics of
      the nursing home as a learning environment. METHOD: Approaching the nursing home
      as a learning environment from a predominantly sociocultural perspective, the
      authors carried out five focus group interviews (December 2011 through February
      2012) with 36 family medicine and elderly care medicine residents during their
      nursing home placements. Data analysis was an iterative process following a
      grounded theory approach. The software ATLAS.ti supported data analysis. RESULTS:
      The authors identified 23 themes in five categories regarding the nursing home as
      a learning environment: organization, medical opportunities, communication,
      teamwork, and supervision. Working and learning in a nursing home was
      characterized by "dealing with less" (i.e., fewer resources), yet the residents
      reported that dealing with less resulted in "learning more." Family medicine and
      elderly care residents from different backgrounds differed in their perceptions
      and specific learning needs. CONCLUSIONS: To the authors' knowledge, this study
      is one of the first to identify characteristics of the nursing home as a learning
      environment. The main challenge in the nursing home is dealing with less, which,
      according to the residents in the present study, often leads to learning more. To
      ensure that learning really happens, the authors call for high-quality
      supervision to support learners in the nursing home environment.

PMID- 24448040
TI  - How clerkship students learn from real patients in practice settings.
AB  - PURPOSE: To explore how undergraduate medical students learn from real patients
      in practice settings, the factors that affect their learning, and how clerkship
      learning might be enhanced. METHOD: In 2009, 22 medical students in the three
      clerkship years of an undergraduate medical program in the United Kingdom made
      119 near-contemporaneous audio diary entries reflecting how they learned from
      real patients. Nineteen attended focus groups; 18 were individually interviewed.
      The authors used a qualitative theory-building methodology with a conceptual
      orientation toward Communities of Practice theory. A learning theorist guided
      selective coding of a constant-comparative analysis. RESULTS: Participants
      learned informally by participating in the communicative practices of workplaces.
      Two overlapping practices, patient care and education, were identified. Patient
      care created learning opportunities, which were enriched when practitioners
      intentionally supported participants' learning. Education, however, was not
      always coupled with patient care. So, talk positioned the boundaries of two
      practices in three configurations: education without patient care, education
      within patient care, and patient care without education. The nature and quality
      of participants' learning depended on how practitioners entered dialogue with
      them and linked the dialogue to authentic patient care. CONCLUSIONS: Findings
      strongly suggest that medical students learn from real patients by participating
      in patient care within an educational practice. Their learning is affected by
      clinicians' willingness to engage in supportive dialogue. Promoting an informal,
      inclusive discourse of workplace learning might enhance clerkship education. This
      approach should take its place alongside-and perhaps ahead of-the currently
      dominant discourse of "clinical teaching."

PMID- 24448041
TI  - Engaging residents and fellows to improve institution-wide quality: the first six
      years of a novel financial incentive program.
AB  - PURPOSE: Teaching hospitals strive to engage physicians in quality improvement
      (QI), and graduate medical education (GME) programs must promote trainee
      competence in systems-based practice (SBP). The authors developed a QI incentive
      program that engages residents and fellows, providing them with financial
      incentives to improve quality while simultaneously gaining SBP experience. In
      this study, they describe and evaluate success in meeting goals set during the
      program's first six years. METHOD: During fiscal years (FYs) 2007-2012, QI
      project goals for all or specific training programs were set collaboratively with
      residents and fellows at the University of California, San Francisco (UCSF). Data
      were collected from administrative databases, via chart abstraction, or through
      independently designed techniques. RESULTS: Approximately 5,275 residents and
      fellows were eligible and participated in the program. A total of 55 projects
      were completed. Among the 18 all-program projects, goals were achieved for 11
      (61%) in three domains: patient satisfaction, quality/safety, and
      operation/utilization. Among the 37 program-specific projects, goals were
      achieved for 28 (76%) in four categories: patient-level interventions, enhanced
      communication, workflow improvements, and effective documentation. Residents and
      fellows earned an average of $800 in bonuses/FY for achieving these goals.
      CONCLUSIONS: Thousands of residents and fellows across disciplines participated
      in real-life, real-time QI during the program's first six years. Participation
      provided an experience that may promote SBP competence and resulted in improved
      quality of care across the UCSF Medical Center. Similar programs may assist
      teaching hospitals and GME programs in meeting current and future QI and training
      mandates.

PMID- 24448042
TI  - What skills should new internal medicine interns have in july? A national survey
      of internal medicine residency program directors.
AB  - PROBLEM: The transition from medical student to intern may cause stress and
      burnout in new interns and the delivery of suboptimal patient care. Despite a
      formal set of subinternship curriculum guidelines, program directors have
      expressed concern regarding the skill set of new interns and the lack of
      standardization in that skill set among interns from different medical schools.
      To address these issues, the Accreditation Council for Graduate Medical
      Education's Next Accreditation System focuses on the development of a competency
      based education continuum spanning undergraduate, graduate, and continuing
      medical education. APPROACH: In 2010, the Clerkship Directors in Internal
      Medicine subinternship task force, in collaboration with the Association of
      Program Directors in Internal Medicine survey committee, surveyed internal
      medicine residency program directors to determine which competencies or skills
      they expected from new medical school graduates. The authors summarized the
      results using categories of interest. OUTCOMES: In both an item rank list and
      free-text responses, program directors were nearly uniform in ranking the skills
      they deemed most important for new interns-organization and time management and
      prioritization skills; effective communication skills; basic clinical skills; and
      knowing when to ask for assistance. NEXT STEPS: Stakeholders should use the
      results of this survey as they develop a milestone-based curriculum for the
      fourth year of medical school and for the internal medicine subinternship. By
      doing so, they should develop a standardized set of skills that meet program
      directors' expectations, reduce the stress of transitions across the educational
      continuum, and improve the quality of patient care.

PMID- 24448043
TI  - How medical students learn from residents in the workplace: a qualitative study.
AB  - PURPOSE: To explore what third-year medical students learn from residents and
      which teaching strategies are used by excellent resident teachers in their
      interactions with students in the clinical workplace environment. METHOD: In this
      multi-institutional qualitative study between January and March 2012, the authors
      conducted focus groups with medical students who were midway through their third
      year. Qualitative analysis was used to identify themes. RESULTS: Thirty-seven
      students participated. Students contributed 228 comments related to teaching
      methods used by residents. The authors categorized these into 20 themes within
      seven domains: role-modeling, focusing on teaching, creating a safe learning
      environment, providing experiential learning opportunities, giving feedback,
      setting expectations, and stimulating learning. Role-modeling, the most
      frequently classified method of teaching in this study, was not included in three
      popular "Resident-as-Teacher" (RAT) models. Strategies including offering
      opportunities for safe practice, involving students in the team, and providing
      experiential learning opportunities were not emphasized in these models either.
      Almost 200 comments representing the knowledge and skills students learned from
      residents were categorized into 33 themes within nine domains: patient care,
      communication, navigating the system, adaptability, functioning as a
      student/resident, lifelong learning, general comments, career/professional
      development, and medical content. Most of these areas are not emphasized in
      popular RAT models. CONCLUSIONS: Residents serve as critically important teachers
      of students in the clinical workplace. Current RAT models are based largely on
      the teaching behaviors of faculty. The content and teaching strategies identified
      by students in this study should serve as the foundation for future RAT program
      development.

PMID- 24448044
TI  - Patient outcomes in teaching versus nonteaching general internal medicine
      services: a systematic review and meta-analysis.
AB  - PURPOSE: Patient care quality appears to be similar when delivered by trainee and
      attending physicians. The authors conducted a systematic review and meta-analysis
      to examine whether outcomes differ for general internal medicine (GIM) patients
      admitted to teaching versus nonteaching services. METHOD: The authors searched
      Medline, EMBASE, and Cochrane Library databases in May 2012 to identify peer
      reviewed, English-language studies with contemporaneous controls comparing
      inpatient mortality, 30-day readmission rate, and/or length of stay (LOS) for
      inpatients admitted to teaching or nonteaching GIM services. RESULTS: The 15
      included studies (1 randomized controlled trial, 14 observational) included
      108,570 patients admitted to U.S. hospitals during 1987-2011. Inpatient mortality
      did not differ between teaching and nonteaching services (13 studies, 108,015
      patients; 2.5% versus 2.8%; OR, 1.07; 95% CI, 0.87-1.32; I = 82%); results were
      consistent in risk-adjusted studies (adjusted OR, 0.91; 95% CI, 0.76-1.08) and
      higher-quality studies (OR, 0.94; 95% CI, 0.73-1.21). There were no differences
      in 30-day readmission rates (11 studies, 106,021 patients; 15.1% versus 13.1%;
      OR, 1.05; 95% CI, 0.93-1.18). Patients on teaching services appeared to have
      longer LOS (11 studies, 82,352 patients; unadjusted mean difference, 0.40 days;
      95% CI, 0.04-0.77 days), but there was substantial heterogeneity (I = 95%).
      Differences disappeared in risk-adjusted studies (mean difference: -0.09 days;
      95% CI, -0.24 to 0.06 days) and in higher-quality studies (mean difference: -0.05
      days; 95% CI, -0.37 to 0.28 days). CONCLUSIONS: There was no convincing evidence
      that outcomes differed substantively for patients admitted to teaching or
      nonteaching GIM services.

PMID- 24448045
TI  - Electronic health record training in undergraduate medical education: bridging
      theory to practice with curricula for empowering patient- and relationship
      centered care in the computerized setting.
AB  - While electronic health record (EHR) use is becoming state-of-the-art, deliberate
      teaching of health care information technology (HCIT) competencies is not keeping
      pace with burgeoning use. Medical students require training to become skilled
      users of HCIT, but formal pedagogy within undergraduate medical education (UME)
      is sparse. How can medical educators best meet the needs of learners while
      integrating EHRs into medical education and practice? How can they help learners
      preserve and foster effective communication skills within the computerized
      setting? In general, how can UME curricula be devised for skilled use of EHRs to
      enhance rather than hinder provision of effective, humanistic health care?Within
      this Perspective, the authors build on recent publications that "set the stage"
      for next steps: EHR curricula innovation and implementation as concrete
      embodiments of theoretical underpinnings. They elaborate on previous calls for
      maximizing benefits and minimizing risks of EHR use with sufficient focus on
      physician-patient communication skills and for developing core competencies
      within medical education. The authors describe bridging theory into practice with
      systematic longitudinal curriculum development for EHR training in UME at their
      institution, informed by Kern and colleagues' curriculum development framework,
      narrative medicine, and reflective practice. They consider this innovation within
      a broader perspective-the overarching goal of empowering undergraduate medical
      students' patient- and relationship-centered skills while effectively
      demonstrating HCIT-related skills. 

PMID- 24448046
TI  - A randomized trial of a three-hour protected nap period in a medicine training
      program: sleep, alertness, and patient outcomes.
AB  - PURPOSE: Protected sleep periods for internal medicine interns have previously
      resulted in increased amount slept and improved cognitive alertness but required
      supplemental personnel. The authors evaluated intern and patient outcomes
      associated with protected nocturnal nap periods of three hours that are personnel
      neutral. METHOD: Randomized trial at Philadelphia Veterans Affairs Medical Center
      (PVAMC) Medical Service and Hospital of the University of Pennsylvania (HUP)
      Oncology Unit. During 2010-2011, four-week blocks were randomly assigned to a
      standard intern schedule (extended duty overnight shifts of up to 30 hours), or
      sequential protected sleep periods (phone sign-out midnight to 3:00 AM [early
      shift] intern 1; 3:00 to 6:00 AM [late shift] intern 2). Participants wore wrist
      Actiwatches, completed sleep diaries, and performed daily assessments of
      behavioral alertness. Between-group comparisons of means and proportions
      controlled for within-person correlations. RESULTS: HUP interns had significantly
      longer sleep durations during both early (2.40 hours) and late (2.44 hours)
      protected periods compared with controls (1.55 hours, P < .0001). At PVAMC sleep
      duration was longer only for the late shift group (2.40 versus 1.90 hours, P <
      .036). Interns assigned to either protected period were significantly less likely
      to have call nights with no sleep and had fewer attentional lapses on the
      Psychomotor Vigilance Test. Differences in patient outcomes between standard
      schedule months versus intervention months were not observed. CONCLUSIONS:
      Protected sleep periods of three hours resulted in more sleep during call and
      reductions in periods of prolonged wakefulness, providing a plausible alternative
      to 16-hour shifts.

PMID- 24448047
TI  - Developing and implementing core competencies for integrative medicine
      fellowships.
AB  - The Consortium of Academic Health Centers for Integrative Medicine defines
      integrative medicine as "the practice of medicine that reaffirms the importance
      of the relationship between practitioner and patient, focuses on the whole
      person, is informed by evidence, and makes use of all appropriate therapeutic
      approaches, health care professionals, and disciplines to achieve optimal health
      and healing." Over the past three decades, the U.S. public increasingly has
      sought integrative medicine approaches. In an effort to train medical
      professionals to adequately counsel patients on the safe and appropriate use of
      these approaches, medical schools and residencies have developed curricula on
      integrative medicine for their trainees. In addition, integrative medicine
      clinical fellowships for postresidency physicians have emerged to provide
      training for practitioners interested in gaining greater expertise in this
      emerging field. Currently, 13 clinical fellowships in integrative medicine exist
      in the United States, and they are predominantly connected to academic medical
      centers or teaching affiliate hospitals. In 2010, the Consortium of Academic
      Health Centers for Integrative Medicine, represented by 56 member academic health
      care institutions with a shared commitment to advance the principles and
      practices of integrative medicine, convened a two-year task force to draft
      integrative medicine fellowship core competencies. These competencies would guide
      fellowship curriculum development and ensure that graduates possessed a common
      body of knowledge, skills, and attitudes. In this article, the authors discuss
      the competencies and the task force's process to develop them, as well as
      associated teaching and assessment methods, faculty development, potential
      barriers, and future directions. 

PMID- 24448048
TI  - Clinical clerkship students' perceptions of (un)safe transitions for every
      patient.
AB  - PURPOSE: As calls for training and accreditation standards around improved
      patient care transitions have recently increased, more publications describing
      medical student education programs on care transitions have appeared. However,
      descriptions of students' experience with care transitions and the
      sender/receiver communication that supports or inhibits them are limited. To fill
      this gap, the authors developed this project to understand students' experiences
      with and perceptions of care transitions. METHOD: At the start of a patient
      safety intersession at the Medical College of Wisconsin (2010), 193 third-year
      medical students anonymously wrote descriptions of critical incidents related to
      care transitions they had witnessed that evoked a strong emotional reaction.
      Descriptions included the emotion evoked, clinical context, and types of
      information exchanged. The authors analyzed the incident descriptions using a
      constant comparative qualitative methodology. RESULTS: Analysis revealed that 111
      of the 121 medical students (92%) who disclosed emotional responses had strong
      negative reactions to unsuccessful transitions, experiencing frustration,
      irritation, fear, and anger. All of these negative emotions were associated with
      lack of or poor communication between the sender and receiver: ambiguous roles
      and responsibilities, insufficient detailing of the patient's medical course,
      inadequate identification of the people involved in the transition, incomplete
      delineation of what the patient needed, and unclear reasons for the transition.
      CONCLUSIONS: Third-year medical students' descriptions of care-transition
      incidents reveal high rates of strong negative emotions and of communication gaps
      that may adversely affect patient care. Results support curricular innovations
      that align students' needs and experiences with safe patient care transitions.

PMID- 24448049
TI  - A core physical exam for medical students: results of a national survey.
AB  - PURPOSE: Medical students are traditionally taught the physical exam as a
      comprehensive battery of maneuvers, yet they express uncertainty about which
      maneuvers are "core" and should be performed routinely on patients and which ones
      should be performed only when clinically indicated. The authors sought to
      determine whether educator consensus existed on the concept and the specifics of
      a core physical exam for students. METHOD: The authors developed a 45-maneuver
      core physical exam to be performed by a medicine clerkship student on every newly
      admitted patient, with the expectation that it would be supplemented by
      clinically indicated additional maneuvers. From 2011 to 2012 they sent surveys to
      physical diagnosis course directors (PDCDs) and internal medicine clerkship
      directors (IMCDs) from all 132 U.S. allopathic medical schools to determine the
      extent of their agreement with the proposed 45 maneuvers and their opinions about
      the concept of a core exam. RESULTS: Seventy-one percent (94/132) of PDCDs and
      63% (83/132) of IMCDs responded to the survey. In total, 84% (111/132) of all
      schools surveyed were represented by either their PDCD or IMCD. Of the 45
      proposed maneuvers, 37 were deemed "core" by a majority of respondents. The
      majority of IMCDs preferred a slightly leaner 37-maneuver core exam than the
      majority of PDCDs, who voted for 41 maneuvers. CONCLUSIONS: Among PDCDs and
      IMCDs, there was openness to teaching medical students a streamlined core
      physical exam to which other maneuvers are added as clinically indicated. These
      educators closely agreed on the maneuvers this core exam should include.

PMID- 24448050
TI  - The Hospital Medicine Reengineering Network (HOMERuN): a learning organization
      focused on improving hospital care.
AB  - Converting the health care delivery system into a learning organization is a key
      strategy for improving health outcomes. Although the collaborative learning
      organization approach has been successful in neonatal intensive care units and
      disease-specific collaboratives, there are few examples in general medicine and
      none in adult medicine that have leveraged the role of hospitalists nationally
      across multiple institutions to implement improvements. The authors describe the
      rationale for and early work of the Hospital Medicine Reengineering Network
      (HOMERuN), a collaborative of hospitals, hospitalists, and multidisciplinary care
      teams founded in 2011 that seeks to measure, benchmark, and improve the
      efficiency, quality, and outcomes of care in the hospital and afterwards. Robust
      and timely evaluation, with learning and refinement of approaches across
      institutions, should accelerate improvement efforts. The authors review HOMERuN's
      collaborative model, which focuses on a community-based participatory approach
      modified to include hospital-based staff as well as the larger community.
      HOMERuN's initial project is described, focusing on care transition measurement
      using perspectives from the patient, caregiver, and providers. Next steps and
      sustainability of the organization are discussed, including benchmarking,
      collaboration, and effective dissemination of best practices to stakeholders. 

PMID- 24448051
TI  - The reliability, validity, and feasibility of multisource feedback physician
      assessment: a systematic review.
AB  - PURPOSE: The use of multisource feedback (MSF) or 360-degree evaluation has
      become a recognized method of assessing physician performance in practice. The
      purpose of the present systematic review was to investigate the reliability,
      generalizability, validity, and feasibility of MSF for the assessment of
      physicians. METHOD: The authors searched the EMBASE, PsycINFO, MEDLINE, PubMed,
      and CINAHL databases for peer-reviewed, English-language articles published from
      1975 to January, 2013. Studies were included if they met the follow ing inclusion
      criteria: used one or more MSF instruments to assess physician performance in
      practice; reported psychometric evidence of the instrument(s) in the form of
      reliability, generalizability coefficients, and construct or criterion-related
      validity; and provided information regarding the administration or feasibility of
      the process in collecting the feedback data. RESULTS: Of the 96 full-text
      articles assessed for eligibility, 43 articles were included. The use of MSF has
      been shown to be an effective method for providing feedback to physicians from a
      multitude of specialties about their clinical and nonclinical (i.e.,
      professionalism, communication, interpersonal relationship, management)
      performance. In general, assessment of physician performance was based on the
      completion of the MSF instruments by 8 medical colleagues, 8 coworkers, and 25
      patients to achieve adequate reliability and generalizability coefficients of
      alpha >= 0.90 and Ep >= 0.80, respectively. CONCLUSIONS: The use of MSF employing
      medical colleagues, coworkers, and patients as a method to assess physicians in
      practice has been shown to have high reliability, validity, and feasibility.

PMID- 24448052
TI  - Role-modeling and medical error disclosure: a national survey of trainees.
AB  - PURPOSE: To measure trainees' exposure to negative and positive role-modeling for
      responding to medical errors and to examine the association between that exposure
      and trainees' attitudes and behaviors regarding error disclosure. METHOD: Between
      May 2011 and June 2012, 435 residents at two large academic medical centers and
      1,187 medical students from seven U.S. medical schools received anonymous,
      electronic questionnaires. The questionnaire asked respondents about (1)
      experiences with errors, (2) training for responding to errors, (3) behaviors
      related to error disclosure, (4) exposure to role-modeling for responding to
      errors, and (5) attitudes regarding disclosure. Using multivariate regression,
      the authors analyzed whether frequency of exposure to negative and positive role
      modeling independently predicted two primary outcomes: (1) attitudes regarding
      disclosure and (2) nontransparent behavior in response to a harmful error.
      RESULTS: The response rate was 55% (884/1,622). Training on how to respond to
      errors had the largest independent, positive effect on attitudes (standardized
      effect estimate, 0.32, P < .001); negative role-modeling had the largest
      independent, negative effect (standardized effect estimate, -0.26, P < .001).
      Positive role-modeling had a positive effect on attitudes (standardized effect
      estimate, 0.26, P < .001). Exposure to negative role-modeling was independently
      associated with an increased likelihood of trainees' nontransparent behavior in
      response to an error (OR 1.37, 95% CI 1.15-1.64; P < .001). CONCLUSIONS: Exposure
      to role-modeling predicts trainees' attitudes and behavior regarding the
      disclosure of harmful errors. Negative role models may be a significant
      impediment to disclosure among trainees.

PMID- 24448053
TI  - Burnout among U.S. medical students, residents, and early career physicians
      relative to the general U.S. population.
AB  - PURPOSE: To compare the prevalence of burnout and other forms of distress across
      career stages and the experiences of trainees and early career (EC) physicians
      versus those of similarly aged college graduates pursuing other careers. METHOD:
      In 2011 and 2012, the authors conducted a national survey of medical students,
      residents/fellows, and EC physicians (<= 5 years in practice) and of a
      probability-based sample of the general U.S. population. All surveys assessed
      burnout, symptoms of depression and suicidal ideation, quality of life, and
      fatigue. RESULTS: Response rates were 35.2% (4,402/12,500) for medical students,
      22.5% (1,701/7,560) for residents/fellows, and 26.7% (7,288/27,276) for EC
      physicians. In multivariate models that controlled for relationship status, sex,
      age, and career stage, being a resident/fellow was associated with increased odds
      of burnout and being a medical student with increased odds of depressive
      symptoms, whereas EC physicians had the lowest odds of high fatigue. Compared
      with the population control samples, medical students, residents/fellows, and EC
      physicians were more likely to be burned out (all P < .0001). Medical students
      and residents/fellows were more likely to exhibit symptoms of depression than the
      population control samples (both P < .0001) but not more likely to have
      experienced recent suicidal ideation. CONCLUSIONS: Training appears to be the
      peak time for distress among physicians, but differences in the prevalence of
      burnout, depressive symptoms, and recent suicidal ideation are relatively small.
      At each stage, burnout is more prevalent among physicians than among their peers
      in the U.S. population.

PMID- 24448054
TI  - A new leadership curriculum: the multiplication of intelligence.
AB  - The authors propose a new model of leadership for the clinical setting. The
      authors' research suggests that there is latent intelligence inside business and
      educational organizations because many leaders operate in a way that shuts down
      the intelligence of others. Such leaders are classified as "Diminishers." In the
      clinical setting this behavior creates a hidden curriculum in medical education,
      passing on unprofessional patterns of behavior to future physicians. Other
      leaders, however, amplify intelligence, produce better outcomes, and grow talent.
      These leaders are classified as "Multipliers." The authors suggest that
      Multiplier leadership should become the standard leadership practice in medical
      schools. Case studies of a Multiplier and a Diminisher are presented and
      illustrate the positive effect these leaders can have on medical education and
      health organizations. 

PMID- 24448055
TI  - Teaching the physical examination: a longitudinal strategy for tomorrow's
      physicians.
AB  - The physical examination is an essential clinical skill. The traditional approach
      to teaching the physical exam has involved a comprehensive "head-to-toe"
      checklist, which is often used to assess students before they begin their
      clinical clerkships. This method has been criticized for its lack of clinical
      context and for promoting rote memorization without critical thinking. In
      response to these concerns, Gowda and colleagues surveyed a national sample of
      clinical skills educators in order to develop a consensus "core" physical exam,
      which they report in this issue. The core physical exam is intended to be
      performed for every patient admitted by students during their medicine clerkships
      and to be supplemented by symptom-driven "clusters" of additional history and
      physical exam maneuvers.In this commentary, the authors review the strengths and
      limitations of this Core + Clusters technique as well as the head-to-toe
      approach. They propose that the head-to-toe still has a place in medical
      education, particularly for beginning students with little knowledge of
      pathophysiology and for patients with vague or multiple symptoms. The authors
      suggest that the ideal curriculum would include teaching both the head-to-toe and
      the Core + Clusters exams in sequence. This iterative approach to physical exam
      teaching would allow a student to assess a patient in a comprehensive manner
      while incorporating more clinical reasoning as further medical knowledge is
      acquired. 

PMID- 24448056
TI  - [Quality standards for ultrasound assessment of the superficial venous system of
      the lower limbs. Report of the French Society for Vascular Medicine].
AB  - The quality standards of the French Society for Vascular Medicine for the
      ultrasound assessment of the superficial venous system of the lower limbs are
      based on the two following requirements: technical know-how (mastering the use of
      ultrasound devices and the method of examination); medical know-how (ability to
      adapt the methods and scope of the examination to its clinical indications and
      purpose and to rationally analyze and interpret its results). AIMS OF THE QUALITY
      STANDARDS: To describe an optimal method of examination in relation to the
      clinical question and hypothesis; to achieve consistent practice, methods,
      glossary terminologies and reporting; to provide good practice reference points
      and to promote a high quality process. THEMES OF THE QUALITY STANDARD: The three
      levels of examination. Their clinical indications and goals. The reference
      standard examination (level 2) and its variants according to clinical needs. The
      minimal content of the examination report, the letter to the referring physician
      (synthesis, conclusion and management suggestions) and iconography. Commented
      glossary (anatomy, hemodynamics, semiology). Technical basis. Ultrasound devices
      settings. We discuss of use of Duplex ultrasound for the assessment of the
      superficial veins of the lower limbs in vascular medicine practice.

PMID- 24448057
TI  - Clinical course and predictive factors for complication of inferior vena cava
      filters.
AB  - RATIONALE: The use of inferior vena cava (IVC) filters is associated with various
      complications. We aimed to elucidate the clinical course and predictive factors
      for complications of IVC filters, especially IVC penetration METHODS: A
      retrospective observational study was performed in 45 adult patients with
      retrievable IVC filters and follow-up computed tomography (CT) between January
      2003 and December 2012. Primary outcomes were the prevalence and predictive
      factors of IVC penetration. Secondary outcome was other complications of IVC
      filters. RESULTS: IVC penetration following filter placement occurred in 87.6% of
      patients, and 57.8% of those involved significant penetration. Embedding of
      filter tips, suggestive of lateral tilting, was observed in 51.1%. Both Vertebral
      body erosions and aortic penetrations were seen in 4.4%, but they were
      asymptomatic. Longer indwelling duration of the IVC filter was significantly
      associated with a higher grade of IVC penetration, and the risk of significant
      IVC penetration increased in patients with the filter indwelling time of more
      than 20 days and an IVC diameter of less than 24.2mm. CONCLUSIONS: In patients
      with a retrievable IVC filter, IVC penetration on CT was common, and significant
      IVC penetration was associated with a longer indwelling time of the IVC filter
      and a lesser IVC diameter.

PMID- 24448058
TI  - Knowledge, satisfaction, and concerns regarding warfarin therapy and their
      association with warfarin adherence and anticoagulation control.
AB  - INTRODUCTION: A better understanding of patients' knowledge, satisfaction and
      concerns can identify deficits and help develop targeted patient education. This
      study aimed to examine patients' knowledge, satisfaction and concerns regarding
      warfarin therapy and assess their association with warfarin adherence and
      international normalized ratio (INR) control. MATERIALS AND METHODS: A cross
      sectional survey was conducted in a convenience sample of patients taking
      warfarin in an anticoagulation clinic. The questionnaire consisted of questions
      on patients' knowledge, satisfaction and concerns regarding warfarin treatment.
      Patients' warfarin refill records and time within the therapeutic INR range were
      retrieved from hospital databases. RESULTS: One hundred and eighty-three patients
      participated in the survey. Patients had inadequate knowledge of warfarin-diet
      and warfarin-drug interactions. Over 40% of the respondents were not satisfied
      with the waiting time to see a pharmacist. The most common concerns of taking
      warfarin were worries about warfarin-drug interactions (36.1%), forgetting to
      take warfarin (26.2%) and worries about side effects (25.7%). Higher satisfaction
      was associated with better knowledge (r=0.24, p=0.001) and fewer concerns (rs=
      0.23, p=0.002). Better knowledge and higher satisfaction were associated with
      higher warfarin adherence (rs=0.21 and 0.16; p=0.01 and 0.046, respectively).
      Better knowledge, higher satisfaction, fewer concerns, and better warfarin
      adherence were associated with good INR control (p=0.003, 0.02, 0.03 and 0.003,
      respectively). CONCLUSIONS: This study highlighted patients' concerns and
      deficits in knowledge regarding warfarin treatment, and also demonstrated their
      association with warfarin adherence and INR control.

PMID- 24448060
TI  - Chocolate consumption and the Nobel prize.

PMID- 24448059
TI  - Influence of the beta-fibrinogen-455G/A polymorphism on development of ischemic
      stroke and coronary heart disease.
AB  - BACKGROUND: Ischemic stroke (IS) and coronary heart disease (CHD) are two
      vascular disorders that are a common cause of death worldwide. Several studies
      have assessed the association of the beta-fibrinogen-455G/A (FGB-455G/A)
      polymorphism and risk of IS and CHD, but the results are still inconsistent. Our
      study aimed to investigate whether the FGB-455G/A polymorphism was associated
      with susceptibility to IS and CHD by using meta-analysis. METHODS: Relevant
      studies were identified from PubMed, Embase and four Chinese database up to July
      2013.Data were analyzed and processed by Stata 11.2. A pooled OR with 95% CI was
      calculated to estimate the strength of the genetic association. Cumulative meta
      analysis was performed to assess the tendency of pooled OR over time. RESULTS: 45
      studies based on a total of 7238 cases and 7395 controls were included in our
      meta-analysis. The results indicated that the FGB-455G/A polymorphism is
      associated with the risk of IS when compared with the dominant model (OR=1.518,
      95%CI=1.279-1.802 for AA+GA vs. GG). In the subgroup analysis by ethnicity,
      significantly elevated risks were associated with the A allele in Asians
      (OR=1.700, 95%CI=1.417-2.040), but not in Caucasians (OR=0.942, 95%CI=0.813
      1.091). Both the hypertension and non-hypertension subgroups reached significant
      results, but no significance was found when stratified according to sex or
      subtype of IS. Results indicate that the FGB-455G/A polymorphism is associated
      with CHD (OR=1.802, 95%CI=1.445-2.246). CONCLUSION: Our meta-analysis suggests
      that the FGB-455G/A polymorphism contributes to susceptibility to IS and CHD.

PMID- 24448061
TI  - Anticholinesterase inhibitory activity of quaternary alkaloids from Tinospora
      crispa.
AB  - Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A
      previous study pointed to the necessary presence of quaternary nitrogens for
      strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids.
      Repeated column chromatography of the vine of Tinospora crispa extract led to the
      isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9
      trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids
      dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine
      (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven
      compounds were isolated and structurally elucidated by spectroscopic analysis.
      Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for
      the first time for this plant. The compounds were tested for AChE inhibitory
      activity using Ellman's method. In the AChE inhibition assay, only columbamine
      (3) showed strong activity with IC50 48.1 uM. The structure-activity
      relationships derived from these results suggest that the quaternary nitrogen in
      the skeleton has some effect, but that a high degree of methoxylation is more
      important for acetylcholinesterase inhibition. 

PMID- 24448062
TI  - Simultaneous determination of 24 antidepressant drugs and their metabolites in
      wastewater by ultra-high performance liquid chromatography-tandem mass
      spectrometry.
AB  - Antidepressants are a new kind of pollutants being increasingly found in
      wastewater. In this study, a fast and sensitive ultra-high performance liquid
      chromatography-tandem mass spectrometry method was developed and validated for
      the analysis of 24 antidepressant drugs and six of their metabolites in
      wastewater. This is the first time that the antidepressant residues in wastewater
      of Beijing (China) were systematically reported. A solid-phase extraction process
      was performed with 3 M cation disk, followed by ultra-high performance liquid
      chromatography-tandem mass spectrometry measurements. The chromatographic
      separation and mass parameters were optimized in order to achieve suitable
      retention time and good resolution for analytes. All compounds were
      satisfactorily determined in one single injection within 20 min. The limit of
      quantification (LOQ), linearity, and extraction recovery were validated. The LOQ
      for analytes were ranged from 0.02 to 0.51 ng/mL. The determination coefficients
      were more than 0.99 within the tested concentration range (0.1-25 ng/mL), and the
      recovery rate for each target compound was ranged from 81.2% to 118% at 1 ng/mL.
      This new developed method was successfully applied to analysis the samples
      collected from Beijing municipal wastewater treatment plants. At least ten target
      antidepressants were found in all samples and the highest mean concentration of
      desmethylvenlafaxin was up to 415.6 ng/L. 

PMID- 24448063
TI  - Synthesis of tetrahydrohonokiol derivates and their evaluation for cytotoxic
      activity against CCRF-CEM leukemia, U251 glioblastoma and HCT-116 colon cancer
      cells.
AB  - Biphenyl neolignans such as honokiol and magnolol, which are the major active
      constituents of the Asian medicinal plant Magnolia officinalis, are known to
      exert a multitude of pharmacological and biological activities. Among these,
      cytotoxic and tumor growth inhibitory activity against various tumour cell lines
      are well-documented. To further elucidate the cytotoxic effects of honokiol
      derivatives, derivatizations were performed using tetrahydrohonokiol as a
      scaffold. The derivatizations comprised the introduction of functional groups,
      e.g., nitro and amino groups, as well as alkylation. This way, 18 derivatives, of
      which 13 were previously undescribed compounds, were evaluated against CCRF-CEM
      leukemia cells, U251 glioblastoma and HCT-116 colon cancer cells. The results
      revealed no significant cytotoxic effects in any of the three tested cell lines
      at a test concentration of 10 uM. 

PMID- 24448064
TI  - Construction of the 1,2-dialkenylcyclohexane framework via Ireland-Claisen
      rearrangement and intramolecular Barbier reaction: application to the synthesis
      of (+/-)-Geijerone and a diastereoisomeric mixture with its 5-epimer.
AB  - The elemene-type terpenoids, which possess various biological activities, contain
      a syn- or anti-1,2-dialkenylcyclohexane framework. An efficient synthetic route
      to the syn- and anti-1,2-dialkenylcyclohexane core and its application in the
      synthesis of (+/-)-geijerone and its diastereomer is reported. Construction of
      the syn- and anti-1,2-dialkenyl moiety was achieved via Ireland-Claisen
      rearrangement of the (E)-allylic ester, and the cyclohexanone moiety was derived
      from the iodoaldehyde via intramolecular Barbier reaction. The synthetic strategy
      allows rapid access to various epimers and analogues of elemene-type products. 

PMID- 24448065
TI  - Two new secondary metabolites from Xylaria sp. cfcc 87468.
AB  - A new isocoumarin glycoside, 3R-(+)-5-O-[6'-O-acetyl]-alpha-D-glucopyranosyl-5
      hydroxymellein (1), and a new phenylethanol glycoside, (-)-phenylethyl-8-O-alpha
      L-rhamno-pyranoside (2), were isolated from the ethyl acetate extract of the
      fungus Xylaria sp. cfcc 87468, together with five known steroids, beta-sitosterol
      (3), stigmast-4-en-3-one (4), ergosterol (5), (22E)-cholesta-4,6,8(14),22-tetraen
      3-one (6), and 4alpha-methyl- ergosta-8(14),24(28)-dien-3beta-ol (7). The
      structures of compounds 1 and 2 were elucidated by MS, extensive 1D and 2D NMR
      spectroscopy, and the circular dichroism (CD) spectroscopy. 

PMID- 24448066
TI  - Inhibition of Epstein-Barr virus lytic cycle by an ethyl acetate subfraction
      separated from Polygonum cuspidatum root and its major component, emodin.
AB  - Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study,
      we examined the ethyl acetate subfraction F3 obtained from P. cuspidatum root and
      its major component, emodin, for their capacity to inhibit the Epstein-Barr virus
      (EBV) lytic cycle. The cell viability was determined by the MTT [3-(4,5
      dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The expression of
      EBV lytic proteins was analyzed by immunoblot, indirect immunofluorescence and
      flow cytometric assays. Real-time quantitative PCR was used to assess the EBV DNA
      replication and the transcription of lytic genes, including BRLF1 and BZLF1.
      Results showed that the F3 and its major component emodin inhibit the
      transcription of EBV immediate early genes, the expression of EBV lytic proteins,
      including Rta, Zta, and EA-D and reduces EBV DNA replication, showing that F3 and
      emodin are potentially useful as an anti-EBV drug. 

PMID- 24448067
TI  - Oxidized fatty acids as inter-kingdom signaling molecules.
AB  - Oxylipins or oxidized fatty acids are a group of molecules found to play a role
      in signaling in many different cell types. These fatty acid derivatives have
      ancient evolutionary origins as signaling molecules and are ideal candidates for
      inter-kingdom communication. This review discusses examples of the ability of
      organisms from different kingdoms to "listen" and respond to oxylipin signals
      during interactions. The interactions that will be looked at are signaling
      between animals and plants; between animals and fungi; between animals and
      bacteria and between plants and fungi. This will aid in understanding these
      interactions, which often have implications in ecology, agriculture as well as
      human and animal health. 

PMID- 24448068
TI  - Overcoming the barriers to the uptake of nonclinical microsampling in regulatory
      safety studies.
AB  - Toxicokinetic analysis is an essential part of nonclinical drug development.
      Advances in bioanalytical techniques have opened up the potential to use smaller
      sample volumes (microsamples) to assess drug exposure in blood, plasma and/or
      serum. Microsampling can increase the amount of nonclinical safety information
      available, improve its validity by linking toxic effects to drug exposure in
      individual animals and represents the most significant opportunity to reduce
      animal use in toxicology studies in the short term. In May 2013, a workshop was
      held with 80 delegates from 33 companies with the aim of sharing information and
      knowledge on microsampling technologies. This article covers the discussions at
      the workshop, current practice in the industry, regulatory experiences and the
      future direction of microsampling across drug development. 

PMID- 24448069
TI  - Layered SiC sheets: a potential catalyst for oxygen reduction reaction.
AB  - The large-scale practical application of fuel cells cannot come true if the high
      priced Pt-based electrocatalysts for oxygen reduction reaction (ORR) cannot be
      replaced by other efficient, low-cost, and stable electrodes. Here, based on
      density functional theory (DFT), we exploited the potentials of layered SiC
      sheets as a novel catalyst for ORR. From our DFT results, it can be predicted
      that layered SiC sheets exhibit excellent ORR catalytic activity without CO
      poisoning, while the CO poisoning is the major drawback in conventional Pt-based
      catalysts. Furthermore, the layered SiC sheets in alkaline media has better
      catalytic activity than Pt(111) surface and have potential as a metal-free
      catalyst for ORR in fuel cells. 

PMID- 24448070
TI  - Papillary fibroelastoma of the tricuspid valve: a perioperative diagnosis.

PMID- 24448071
TI  - Surgical treatment for chronic type B aortic dissection originating from a
      Kommerell diverticulum with right-sided aortic arch.

PMID- 24448072
TI  - Type-B interruption of the aortic arch with a giant aortic arch aneurysm in an
      adult.

PMID- 24448073
TI  - Late aorto-left ventricular fistula following aortic valve replacement for
      infective endocarditis.

PMID- 24448074
TI  - Formation of multiple conduit aneurysms following Matrix P conduit implantation
      in a boy with tetralogy of Fallot and pulmonary atresia.
AB  - We report on a 6-year old boy with tetralogy of Fallot and pulmonary atresia in
      whom a 16 m Matrix P conduit was implanted between the pulmonary artery and the
      right ventricle at the age of 16 months. Five years later he developed severe
      stenosis of the distal conduit anastomosis. The notable findings were several
      aneurysms of the conduit proximal to the distal stenosis within the high-pressure
      region. The wall of the aneurysms contained xenogeneic conduit tissue without
      inflammatory or foreign-body response. We believe that aneurysm formation of the
      conduit was a result of fatigue of the conduit wall under suprasystemic pressure.

PMID- 24448075
TI  - Impact of diabetes mellitus and renal insufficiency on 5-year mortality following
      coronary artery bypass graft surgery: a cohort study of 4869 UK patients.
AB  - OBJECTIVES: Diabetes mellitus (DM) and renal impairment (RI) are both independent
      predictors of mortality after coronary artery bypass graft surgery (CABG). The
      two conditions often coexist, yet the impact on long-term prognosis after CABG of
      each factor relative to the other and the two in combination is uncertain.
      METHODS: We undertook a prospective cohort study of 4869 patients who underwent
      CABG between 2003 and 2007. The cohort was divided into four groups according to
      preoperative diabetic status and renal function: patients without either DM or RI
      (reference group), patients with DM alone, patients with RI alone and patients
      with both DM and RI. Clinical outcomes were compared between groups. Patients
      receiving renal replacement therapy were excluded. The primary outcome was 5-year
      all-cause mortality. RESULTS: The crude 5-year all-cause mortality rate was 9.0%
      for patients in the reference group, 11.1% for patients with DM alone, 20.3% for
      patients with RI alone and 28.5% for patients with both DM and RI (P < 0.0001).
      Five-year survival adjusted for potential confounding factors was significantly
      worse for patients with DM (hazard ratio (HR) 1.30; 95% confidence interval (CI)
      1.06-1.59), patients with RI (HR 1.32; 95% CI 1.08-1.61) and patients with both
      DM and RI (HR 2.04; 95% CI 1.65-2.53) when compared with patients with neither
      condition. CONCLUSIONS: Preoperative DM and RI were important predictors of 5
      year mortality after CABG. Patients with RI alone had a higher mortality rate
      than patients with DM alone, but this difference was largely accounted for by age
      and other comorbidities. The combination of DM and RI doubled the 5-year
      mortality rate after CABG independently of potential confounding factors.

PMID- 24448076
TI  - Real-time graft flow assessment using epigraftic ultrasonography during coronary
      artery bypass grafting.
AB  - OBJECTIVES: Real-time graft flow assessment in the operative field has been
      performed to ascertain the patency in coronary artery bypass grafting (CABG).
      This study aims to evaluate the efficacy of graft flow assessment by epigraftic
      ultrasonography. METHODS: CABG was performed in 135 patients from January 2010 to
      December 2012. One hundred and ten patients (81.4%) underwent both real-time
      graft flow measurement using epigraftic ultrasonography and coronary angiography
      (CAG) with a total of 249 grafts. Parameters were obtained from flow velocity
      curves in all grafts. The grafts were divided into two groups: patent grafts
      (Group A) and failing grafts (Group B). All parameters were compared in these two
      groups. Logistic regression analysis was performed to detect the predictors of
      graft failure and receiver operating characteristic (ROC) curve analysis was used
      to calculate the optimal cut-off value of the predictors of graft failure.
      RESULTS: The overall patency as measured by CAG of the grafts was 97.2%
      (242/249). Logistic regression analysis revealed that the percentage of systolic
      and diastolic reverse flow (%sRF, %dRF) as well as the pulsatility index (PI)
      were predictors of early postoperative graft failure. ROC curve analysis revealed
      that mean velocity <12.5 cm/s, %sRF >9.3%, %dRF >4.1% and PI >4.4 were predictors
      of early graft failure. CONCLUSIONS: In this series, epigraftic ultrasonography
      depicted graft flow clearly. Epigraftic ultrasonography is a useful tool to
      predict graft failure during CABG. This technique is easily performed using a
      conventional linear ultrasound transducer.

PMID- 24448077
TI  - Spinning up the polymorphs of calcium carbonate.
AB  - Controlling the growth of the polymorphs of calcium carbonate is important in
      understanding the changing environmental conditions in the oceans. Aragonite is
      the main polymorph in the inner shells of marine organisms, and can be readily
      converted to calcite, which is the most stable polymorph of calcium carbonate.
      Both of these polymorphs are significantly more stable than vaterite, which is
      the other naturally occurring polymorph of calcium carbonate, and this is
      reflected in its limited distribution in nature. We have investigated the effect
      of high shear forces on the phase behaviour of calcium carbonate using a vortex
      fluidic device (VFD), with experimental parameters varied to explore calcium
      carbonate mineralisation. Variation of tilt angle, rotation speed and temperature
      allow for control over the size, shape and phase of the resulting calcium
      carbonate. 

PMID- 24448078
TI  - Helicobacter pylori-driven modulation of NK cell expansion, intracellular
      cytokine expression and cytotoxic activity.
AB  - During Helicobacter pylori (Hp) infections, innate immune cells may be positively
      or negatively modulated by Hp compounds or by Hp-induced cytokines. We have shown
      previously that the natural cytotoxic activity of PBMC was lower in Hp-infected
      [Hp(+)] than Hp-uninfected individuals [Hp(-)]. Here, we asked whether the Hp
      modulated cytotoxic amplitude is associated with changes in the number of NK
      cells, their activation or intracellular cytokine expression. Flow cytometry
      immunophenotyping of PBMC was performed with regard to the surface receptors CD3,
      CD56 and CD25, and intracellular cytokine expression of IL-2, IFN-gamma and IL-10
      after in vitro stimulation with Hp glycine acid extract (GE), Hp LPS or standard
      Escherichia coli LPS. Hp GE-driven enhancement of lymphocyte cytotoxic activity
      was associated with the expansion of CD3(-)CD56(+)CD25(+) NK cells and the up
      regulation of IFN-gamma and/or IL-2 synthesis, up to the higher level in Hp(-)
      than in Hp(+), while Hp LPS-mediated decrease in lymphocyte cytotoxicity was
      accompanied by the lack of CD3(-)CD56(+)CD25(+) NK propagation, the inhibition of
      pro-inflammatory cytokine expression and intense expansion of IL-10-producing NK
      cells. Thus, the cytotoxic and cytokine activities of NK cells were dependent on
      the type of antigenic challenge and the Hp status, that is, NK cells could be
      modulated positively by Hp GE Ags and negatively by Hp LPS.

PMID- 24448079
TI  - Unbalanced anesthesia? "Cleveland's ether" and "political oxygen".

PMID- 24448080
TI  - ASA's inaugural Distinguished Service Award recipient: Paul M. Wood, M.D.

PMID- 24448081
TI  - Tiffany's stained glass memorial to Dr. and Mrs. Horace Wells: righteousness and
      peace.

PMID- 24448082
TI  - Sugammadex after the reappearance of four twitches during train-of-four
      stimulation: monitoring and dose considerations.

PMID- 24448083
TI  - In reply.

PMID- 24448084
TI  - Influence of body mass index and epidural anesthesia on lung function.

PMID- 24448085
TI  - Association between intraoperative ventilation strategies and postoperative
      pulmonary outcomes in surgical patients.

PMID- 24448086
TI  - Lung-protective ventilation during general anesthesia: what about the oxygen?

PMID- 24448087
TI  - In reply.

PMID- 24448088
TI  - Vitamins in nitrous oxide randomized trial: a few concerns.

PMID- 24448089
TI  - In reply.

PMID- 24448095
TI  - Infographics in anesthesiology: complex information for anesthesiologists
      presented quickly and clearly.

PMID- 24448096
TI  - Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid
      cells.
AB  - The innate and adaptive immune systems in the intestine cooperate to maintain the
      integrity of the intestinal barrier and to regulate the composition of the
      resident microbiota. However, little is known about the crosstalk between the
      innate and adaptive immune systems that contribute to this homeostasis. We find
      that CD4+ T cells regulate the number and function of barrier-protective innate
      lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs),
      Reg3gamma and Reg3beta. RAG1-/- mice lacking T and B cells had elevated ILC
      numbers, interleukin-22 (IL-22) production, and AMP expression, which were
      corrected by replacement of CD4+ T cells. Major histocompatibility class II-/-
      (MHCII-/-) mice lacking CD4+ T cells also had increased ILCs, IL-22, and AMPs,
      suggesting that negative regulation by CD4+ T cells occurs at steady state. We
      utilized transfers and genetically modified mice to show that reduction of IL-22
      is mediated by conventional CD4+ T cells and is T-cell receptor dependent. The IL
      22-AMP axis responds to commensal bacteria; however, neither the bacterial
      repertoire nor the gross localization of commensal bacteria differed between
      MHCII+/- and MHCII-/- littermates. These data define a novel ability of CD4+ T
      cells to regulate intestinal IL-22-producing ILCs and AMPs. 

PMID- 24448097
TI  - A role for the pattern recognition receptor Nod2 in promoting recruitment of
      CD103+ dendritic cells to the colon in response to Trichuris muris infection.
AB  - The ability of the colon to generate an immune response to pathogens, such as the
      model pathogen Trichuris muris, is a fundamental and critical defense mechanism.
      Resistance to T. muris infection is associated with the rapid recruitment of
      dendritic cells (DCs) to the colonic epithelium via epithelial chemokine
      production. However, the epithelial-pathogen interactions that drive chemokine
      production are not known. We addressed the role of the cytosolic pattern
      recognition receptor Nod2. In response to infection, there was a rapid influx of
      CD103(+)CD11c(+) DCs into the colonic epithelium in wild-type (WT) mice, whereas
      this was absent in Nod2(-/-) animals. In vitro chemotaxis assays and in vivo
      experiments using bone marrow chimeras of WT mice reconstituted with Nod2(-/-)
      bone marrow and infected with T. muris demonstrated that the migratory function
      of Nod2(-/-) DCs was normal. Investigation of colonic epithelial cell (CEC)
      innate responses revealed a significant reduction in epithelial production of the
      chemokines CCL2 and CCL5 but not CCL20 by Nod2-deficient CECs. Collectively,
      these data demonstrate the importance of Nod2 in CEC responses to infection and
      the requirement for functional Nod2 in initiating host epithelial chemokine
      mediated responses and subsequent DC recruitment and T-cell responses following
      infection. 

PMID- 24448098
TI  - IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and
      survival.
AB  - Natural killer T (NKT) cells are innate-like T cells that rapidly recognize
      pathogens and produce cytokines that shape the ensuing immune response. IL-17
      producing NKT cells are enriched in barrier tissues, such as the lung, skin, and
      peripheral lymph nodes, and the factors that maintain this population in the
      periphery have not been elucidated. Here we show that NKT17 cells deviate from
      other NKT cells in their survival requirements. In contrast to conventional NKT
      cells that are maintained by IL-15, RORgammat(+) NKT cells are IL-15 independent
      and instead rely completely on IL-7. IL-7 initiates a T-cell receptor-independent
      (TCR-independent) expansion of NKT17 cells, thus supporting their homeostasis.
      Without IL-7, survival is dramatically impaired, yet residual cells remain
      lineage committed with no downregulation of RORgammat evident. Their preferential
      response to IL-7 does not reflect enhanced signaling through STAT proteins, but
      instead is modulated via the PI3K/AKT/mTOR signaling pathway. The ability to
      compete for IL-7 is dependent on high-density IL-7 receptor expression, which
      would promote uptake of low levels of IL-7 produced in the non-lymphoid sites of
      lung and skin. This dependence on IL-7 is also reported for RORgammat(+) innate
      lymphoid cells and CD4(+) Th17 cells, and suggests common survival requirements
      for functionally similar cells. 

PMID- 24448099
TI  - Human rhinovirus-induced ISG15 selectively modulates epithelial antiviral
      immunity.
AB  - Human rhinovirus (HRV) infections trigger exacerbations of lower airway diseases.
      HRV infects human airway epithelial cells and induces proinflammatory and
      antiviral molecules that regulate the response to HRV infection. Interferon (IFN)
      stimulated gene of 15 kDa (ISG15) has been shown to regulate other viruses. We
      now show that HRV-16 infection induces both intracellular epithelial ISG15
      expression and ISG15 secretion in vitro. Moreover, ISG15 protein levels increased
      in nasal secretions of subjects with symptomatic HRV infections. HRV-16-induced
      ISG15 expression is transcriptionally regulated via an IFN regulatory factor
      pathway. ISG15 does not directly alter HRV replication but does modulate immune
      signaling via the viral sensor protein RIG-I to impact production of CXCL10,
      which has been linked to innate immunity to viruses. Extracellular ISG15 also
      alters CXCL10 production. We conclude that ISG15 has a complex role in host
      defense against HRV infection, and that additional studies are needed to clarify
      the role of this molecule. 

PMID- 24448100
TI  - Comparative use of different techniques for leak and bleeding prevention during
      laparoscopic sleeve gastrectomy: a multicenter study.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an approved primary
      procedure for morbid obesity, but it is associated with serious complications,
      such as staple line leaks and bleeding. The objective of this study was to assess
      the effectiveness of staple line reinforcement (SLR) in reducing leaks and
      bleeding after LSG. METHODS: A total of 1162 patients underwent LSG (305 males,
      857 females). The mean age was 43.7 years and the mean body mass index was 48
      kg/m(2). The patients were divided into 6 groups based on the type of SLR,
      including a no-SLR control group, with evaluation of leaking and bleeding risk
      and correlation of patients' characteristics with complications. RESULTS: A total
      of 189 patients underwent LSG without reinforcement. The SLR method was
      oversewing in 476 patients, bovine pericardium in 312, synthetic polyester in 76,
      glycolide/trimethylene copolymer in 63, and thrombin matrix in 46. The overall
      leak frequency was 2.8%; higher with synthetic polyester (7.8%), 4.8% with no
      reinforcement, and lower with bovine pericardium strips (.3%; P<.01).
      Postoperative hemorrhage occurred in 35 patients (3%), with a higher frequency
      being observed without SLR (13.7%; P = .02). Only diabetes was a risk-factor for
      a leak (P< .01). CONCLUSION: SLR with bovine pericardium strips significantly
      reduced the leak risk. Postoperative bleeding was significantly lower with all
      SLR-methods, although there was no significant difference among the various
      techniques. Patients with type II diabetes had a higher risk of staple line leak
      after LSG. Further randomized, controlled studies are needed to improve our
      understanding of the efficacy of SLR during LSG.

PMID- 24448101
TI  - Treatment of severe postRYGB hyperinsulinemic hypoglycemia with pasireotide: a
      comparison with octreotide on insulin, glucagon, and GLP-1.

PMID- 24448102
TI  - Revealing tact within postnatal care.
AB  - In this article, we explore the nature of good postnatal care through a
      hermeneutic unpacking of the notion of tact, drawing on the philosophical
      writings of Heidegger, Gadamer, and van Manen. The tactful encounters considered
      were from a hermeneutic research study within a small, rural birthing center in
      New Zealand. Insights drawn from the analysis were as follows: the openness of
      listening, watching and being attuned that builds a positive mode of engagement,
      recognizing that the distance the woman needs from her nurse/midwife is a call of
      tact, that tact is underpinned by a spirit of care, within tact there are moods
      and tact might require firmness, and that all of these factors come together to
      build trust. We conclude that the attunement of tact requires that the staff
      member has time to spend with a woman, enough energy to engage, and a spirit of
      care. Women know that tactful practice builds their confidence and affects their
      mothering experience. Tact cannot be assumed; it needs to be nurtured and
      sheltered. 

PMID- 24448103
TI  - Post hoc analysis of the efficacy and safety of desvenlafaxine 50 mg/day in a
      randomized, placebo-controlled study of perimenopausal and postmenopausal women
      with major depressive disorder.
AB  - OBJECTIVE: This post hoc analysis assessed the efficacy of desvenlafaxine 50
      mg/day for treating major depressive disorder in perimenopausal versus
      postmenopausal women enrolled in a 10-week, double-blind, placebo-controlled
      study. METHODS: Perimenopausal and postmenopausal women (40-70 y) diagnosed with
      major depressive disorder were randomly assigned to receive desvenlafaxine 50
      mg/day or placebo. Changes from baseline in the primary efficacy variable (17
      item Hamilton Rating Scale for Depression [HAM-D17] score, week 8) and in other
      secondary efficacy variables (Sheehan Disability Scale and Menopause Rating
      Scale) were analyzed using analysis of covariance with treatment, region, and
      baseline in the model. Clinical Global Impressions-Improvement Scale was analyzed
      with the Cochran-Mantel-Haenszel test. Response and remission rates were
      evaluated using logistic regression with treatment, region, and baseline HAM-D17
      in the model. RESULTS: Of 426 women (desvenlafaxine, n = 216; placebo, n = 210)
      included in this analysis, 135 (32%) were perimenopausal and 291 (68%) were
      postmenopausal at baseline. In both subgroups, improvement from baseline in HAM
      D17 scores was significantly greater for desvenlafaxine 50 mg/day than for
      placebo. Menopause status and time since menopause did not significantly affect
      HAM-D17 total score. The drug-placebo difference in Sheehan Disability Scale
      scores was significant in perimenopausal women (-9.3 vs. -5.1, P < 0.001) but not
      in postmenopausal women (-8.8 vs. -8.1). Menopause Rating Scale and Clinical
      Global Impressions-Improvement Scale scores were significantly improved with
      desvenlafaxine in postmenopausal women. CONCLUSIONS: Desvenlafaxine 50 mg/day is
      effective in treating depression in both perimenopausal and postmenopausal women.
      Placebo response on measures of functional impairment is lower in perimenopausal
      women than in postmenopausal women, resulting in a greater apparent treatment
      benefit with desvenlafaxine among perimenopausal women.

PMID- 24448104
TI  - Cigarettes, genetic background, and menopausal timing: the presence of single
      nucleotide polymorphisms in cytochrome P450 genes is associated with increased
      risk of natural menopause in European-American smokers.
AB  - OBJECTIVE: This study aims to evaluate associations between variations in genes
      involved in the metabolism of environmental chemicals and steroid hormones and
      risk of menopause in smokers. METHODS: Survival analysis was performed on 410
      eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a
      cohort study of late-reproductive-age women. Single nucleotide polymorphisms at
      the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3
      Leu432Val, and CYP3A4*1B. RESULTS: Significant interactions between smoking and
      single nucleotide polymorphisms were observed in European-American carriers of
      CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared
      with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a
      greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR],
      2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y,
      respectively). No association between smoking and menopause was identified in
      CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for
      menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median
      time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in
      CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03
      2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84;
      median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers
      (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had
      the greatest risk of menopause entry. CONCLUSIONS: Our finding that the risk of
      menopause entry in European-American smokers varies depending on genetic
      background represents a novel gene-environment interaction in reproductive aging.

PMID- 24448106
TI  - Mood disorders in midlife women: understanding the critical window and its
      clinical implications.
AB  - OBJECTIVE: Menopausal transition and early postmenopausal years have been
      described as a "window of vulnerability" for the development of depressive
      symptoms or depression (new or recurrent) in some women. This article aims to
      review contributing factors to the emergence of menopause-related depression,
      some of the key challenges to its proper identification and management, and
      evidence on effective treatment strategies. METHODS: A body of evidence (animal
      data, epidemiologic studies, and clinical studies) was reviewed to disentangle
      some of the complex interactions between changes in sex hormones and reproductive
      function, physical health, and mood in midlife women. Special focus was given to
      the window of vulnerability framework. RESULTS: Despite evidence of a critical
      window for new onset of depression, a prior depressive episode (particularly if
      related to reproductive events) remains the strongest predictor of mood symptoms
      or depression during midlife years. Vasomotor symptoms, anxiety, and other health
      related issues also modulate the risk for depression. Mechanistically, estrogen
      plays an important role in mood and cognitive regulation. Transdermal estradiol,
      as well as serotonergic and noradrenergic antidepressants, have shown efficacy in
      the management of depression in this population. Other evidence-based treatment
      options (hormonal, pharmacologic, and behavioral) are available to clinicians and
      health professionals. CONCLUSIONS: A more comprehensive diagnostic approach
      should be used in symptomatic midlife women. Ultimately, researchers hope to
      develop preventive strategies and treatments that could be tailored to multiple
      symptom domains and improve overall functioning.

PMID- 24448105
TI  - Association between personality traits and DSM-IV diagnosis of insomnia in peri-
      and postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to determine the role of personality factors
      in the development of DSM-IV insomnia coincident with perimenopause. METHODS:
      Perimenopausal women (35 women with DSM-IV insomnia and 28 women with self
      reported normal sleep) underwent clinical assessments and completed menopause
      related questionnaires, the NEO Five Factor Inventory and the Structured
      Interview for DSM-IV Personality. Logistic regressions determined whether
      personality factors and hot flash-related interference were associated with an
      insomnia diagnosis concurrent with the menopausal transition. RESULTS: Women with
      insomnia reported higher neuroticism, lower agreeableness, and lower
      conscientiousness than controls on the NEO Five Factor Inventory. Moreover, women
      with insomnia were more likely to meet DSM-IV criteria for cluster C personality
      disorders, particularly obsessive-compulsive personality disorder, on the
      Structured Interview for DSM-IV Personality. Women with insomnia were more likely
      to have had a past depressive episode and a history of severe premenstrual
      symptoms. Findings from regressions revealed that higher neuroticism and greater
      interference from hot flashes were associated with insomnia classification even
      after controlling for history of depression, suggesting that sensitivity to hot
      flashes and a greater degree of neuroticism are independent contributors toward
      establishing which women are most likely to have sleep problems during
      perimenopause. CONCLUSIONS: Findings show the relevance of personality factors,
      particularly neuroticism and obsessive-compulsive personality, to a woman's
      experience of insomnia as she goes through the menopausal transition.

PMID- 24448107
TI  - Estrogen treatment does not reduce fractures?

PMID- 24448108
TI  - Are researchers studying the wrong kind of hot flashes?

PMID- 24448109
TI  - Observer bias in randomized clinical trials with time-to-event outcomes:
      systematic review of trials with both blinded and non-blinded outcome assessors.
AB  - BACKGROUND: We wanted to evaluate the impact of nonblinded outcome assessors on
      estimated treatment effects in time-to-event trials. METHODS: Systematic review
      of randomized clinical trials with both blinded and nonblinded assessors of the
      same time-to-event outcome. Two authors agreed on inclusion of trials and
      outcomes. We compared hazard ratios based on nonblinded and blinded assessments.
      A ratio of hazard ratios (RHR)<1 indicated that nonblinded assessors generated
      more optimistic effect estimates. We pooled RHRs with inverse variance random
      effects meta-analysis. RESULTS: We included 18 trials. Eleven trials (1969
      patients) with subjective outcomes provided hazard ratios, RHR 0.88 (0.69 to
      1.12), (I2=44%, P=0.06), but unconditional pooling was problematic because of
      qualitative heterogeneity. Four atypical cytomegalovirus retinitis trials
      compared experimental oral administration with control intravenous administration
      of the same drug, resulting in bias favouring the control intervention, RHR 1.33
      (0.98 to 1.82). Seven trials of cytomegalovirus retinitis, tibial fracture and
      multiple sclerosis compared experimental interventions with standard control
      interventions, e.g. placebo, no-treatment or active control, resulting in bias
      favouring the experimental intervention, RHR 0.73 (0.57 to 0.93), indicating an
      average exaggeration of nonblinded hazard ratios by 27% (7% to 43%). CONCLUSIONS:
      Lack of blinded outcome assessors in randomized trials with subjective time-to
      event outcomes causes high risk of observer bias. Nonblinded outcome assessors
      typically favour the experimental intervention, exaggerating the hazard ratio by
      an average of approximately 27%; but in special situations, nonblinded outcome
      assessors favour control interventions, inducing a comparable degree of observer
      bias in the reversed direction.

PMID- 24448110
TI  - Enantioselective construction of vicinal all-carbon quaternary centers via
      catalytic double asymmetric decarboxylative allylation.
AB  - We report a catalytic stereoconvergent construction of vicinal all-carbon
      quaternary centers via double stereoablative enantioselective alkylation of a
      mixture having racemic and meso diastereomers of esters to afford exceptional
      levels of diastereo- (up to 17 : 1) and enantioselectivity (up to >99% ee). The
      strategy offers an efficient and general approach to dimeric cyclotryptamine
      alkaloids sharing a labile C(3a)-C(3a') sigma-bond in the
      hexahydropyrroloindoline core.

PMID- 24448111
TI  - Iodine supplementation in the newborn.
AB  - Iodine deficiency can be defined as the world's greatest single cause of
      preventable brain damage. Fetal and neonatal hypothyroidism, caused by iodine
      deficiency can be prevented prior to conception and then during pregnancy and
      lactation when an adequate iodine supplementation is ensured. Extremely low birth
      weight preterm babies risk having a negative iodine balance status in the first
      weeks of life, exacerbating the hypothyroxinaemia of the prematurity. It is
      important to ensure that these babies are provided with an adequate iodine intake
      from the first days of life. Mothers and newborns should avoid environmental
      iodine excess during pregnancy or lactation. 

PMID- 24448113
TI  - Folding and unfolding thermodynamics of the TC10b Trp-cage miniprotein.
AB  - We examine the folding-unfolding of a variant of the Trp-cage, known as TC10b,
      and compare structural stability, dynamics, and thermodynamics with that of the
      TC5b variant, using replica exchange molecular dynamics (REMD). The TC10b variant
      was designed to have larger helical stability by the substitution of amino acids
      with greater alpha helical propensities in the N-terminal region. Experiments
      have shown TC10b to possess larger overall stability than TC5b. Simulations
      starting from unbiased, unfolded initial conditions are run for 1 MUs per
      replica. The calculations show a higher melting temperature for TC10b than TC5b,
      and suggest a more ordered folded structure through the elimination of a substate
      found in the folded ensemble of TC5b. We model the difference in Gibbs free
      energy, DeltaG(P,T), of folding using the bootstrap statistical method, which is
      used to calculate uncertainties associated with the thermodynamic parameters for
      both variants of the Trp-cage. We find that while the shape of the area for which
      the protein is stability folded is elliptical for TC5b, there is a degree of
      uncertainty associated with that of TC10b, with one model suggesting elliptical
      and another suggesting hyperbolic. This model suggests that at high pressures,
      TC5b can experience pressure denaturation, but TC10b may not. 

PMID- 24448112
TI  - Micro-a-fluidics ELISA for rapid CD4 cell count at the point-of-care.
AB  - HIV has become one of the most devastating pathogens in human history. Despite
      fast progress in HIV-related basic research, antiretroviral therapy (ART) remains
      the most effective method to save AIDS patients' lives. Unfortunately, ART cannot
      be universally accessed, especially in developing countries, due to the lack of
      effective treatment monitoring diagnostics. Here, we present an inexpensive,
      rapid and portable micro-a-fluidic platform, which can streamline the process of
      an enzyme-linked immunosorbent assay (ELISA) in a fully automated manner for CD4
      cell count. The micro-a-fluidic CD4 cell count is achieved by eliminating
      operational fluid flow via "moving the substrate", as opposed to "flowing liquid"
      in traditional ELISA or microfluidic methods. This is the first demonstration of
      capturing and detecting cells from unprocessed whole blood using the enzyme
      linked immunosorbent assay (ELISA) in a microfluidic channel. Combined with cell
      phone imaging, the presented micro-a-fluidic ELISA platform holds great promise
      for offering rapid CD4 cell count to scale up much needed ART in resource
      constrained settings. The developed system can be extended to multiple areas for
      ELISA-related assays. 

PMID- 24448114
TI  - Diastereoselective synthesis of a bicyclic beta-lactam with penicillin G-like
      spectrum of activity by carbonylation of an acyclic diaminocarbene.
AB  - Diisopropylamino-cis-2,6-dimethylpiperidinocarbene reacts regio- and
      diastereoselectively with CO to afford a bicyclic beta-lactam with 100% atom
      efficiency, whose spectrum of activity resembles that of penicillin G or
      amoxicillin. 

PMID- 24448115
TI  - Looking forward and looking backward--making impact with impact factor.

PMID- 24448117
TI  - Platelet-rich plasma in dermatology: boon or a bane?
AB  - There has been a recent spurt in application of platelet-rich plasma (PRP) in
      dermatology and aesthetic medicine. However, the details regarding use of PRP in
      various dermatological indications ranging from hair restoration to chronic
      ulcers are dispersed in literature, herein we have tried to focus all under one
      heading. Overall, PRP seems to be a promising therapeutic modality but the level
      of evidence as of now, from the available published data is low. This review will
      also stimulate readers to carry out well designed, larger population based
      trials, so as to validate its use in dermatology practice. 

PMID- 24448118
TI  - Prevalence and clinical patterns of psoriatic arthritis in Indian patients with
      psoriasis.
AB  - BACKGROUND: The prevalence and clinical patterns of psoriatic arthritis (PsA)
      varies in different parts of the world and there is little clinical and
      epidemiological data from the Indian subcontinent. AIMS: Our study was designed
      to evaluate the prevalence and clinical patterns of PsA in Indian patients.
      METHODS: This was a non-interventional, cross-sectional study, in which 1149
      consecutive psoriasis patients seen over 1 year were screened for PsA according
      to classification of psoriatic arthritis (CASPAR) criteria. Demographic and
      disease parameters were recorded including Psoriasis Area and Severity Index
      (PASI), Nail Psoriasis Severity Index (NAPSI), and number of swollen and tender
      joints. RESULTS: Among 1149 patients with psoriasis, 100 (8.7%) patients had PsA,
      of which 83% were newly diagnosed. The most common pattern was symmetrical
      polyarthritis (58%), followed by spondyloarthropathy 49%, asymmetric
      oligoarthritis (21%), isolated spondyloarthropathy (5%), predominant distal
      interphalangeal arthritis (3%), and arthritis mutilans (1%). Enthesitis and
      dactylitis were present in 67% and 26% of cases, respectively. The mean number of
      swollen and tender joints were 3.63+/-3.59 (range, 0-22) and 7.76+/-6.03 (range,
      1-26), respectively. Nail changes were present in 87% of the cases. The median
      PASI and NAPSI of the subjects with PsA was 3.6 and 20, respectively. There was
      no significant correlation of number of swollen/tender joints with PASI or NAPSI.
      CONCLUSION: There is a relatively low prevalence of PsA among Indian psoriasis
      patients presenting to dermatologists. No correlation was found between the
      severity of skin and nail involvement and articular disease.

PMID- 24448119
TI  - Pruritic porokeratotic peno-scrotal plaques: porokeratosis or porokeratotic
      epidermal reaction pattern? A report of 10 cases.
AB  - BACKGROUND: Porokeratosis restricted to the genital region is rare with few cases
      described in the literature. Cases of porokeratosis restricted to the genital
      region are similar to plaque type of porokeratosis of Mibelli seen elsewhere on
      the body. We encountered 10 young males with pruritic plaques restricted to the
      peno-scrotal region, which clinically were not diagnosed as porokeratosis, but on
      biopsy revealed multiple cornoid lamellae, some of which were seen to arise from
      eccrine and follicular structures. AIMS: The aim of this study is to study
      lesions restricted to the peno-scrotal region in males, which on biopsy showed
      cornoid lamellae suggestive of porokeratosis. METHODS: Retrospective analysis of
      available data of patients who were rendered a histological diagnosis of genital
      porokeratosis. The database consisted of biopsies received in private
      consultation by the first author in the period January 2000 to March 2013.
      RESULTS: Ten young men, 8 in their third decade, presented with pruritic plaques
      restricted to the peno-scrotal region of variable duration. The lesions were well
      demarcated on the penis, but ill-defined with a rough granular surface on the
      scrotum. None of patients were diagnosed clinically as porokeratosis. The lesions
      were poorly responsive to topical steroid/antifungal treatment, but two patients
      showed partial improvement with oral isotretinoin. Biopsy in nine patients
      revealed multiple cornoid lamellae involving epidermis (6) and adnexal structures
      (3). One patient had a single cornoid lamella. CONCLUSION: The clinical and
      histological presentation of these patients is different from typical genital
      porokeratosis described in the literature and we postulate that these patients
      have an unusual porokeratotic reaction pattern of the epidermis with multiple
      cornoid lamellae.

PMID- 24448120
TI  - Randomized controlled study to evaluate the effectiveness of dexamethasone oral
      minipulse therapy versus oral minocycline in patients with active vitiligo
      vulgaris.
AB  - BACKGROUND: Oral minocycline has been recently shown to halt disease progression
      in active vitiligo. AIMS: The present study was planned to compare the efficacy
      and tolerability of oral minocycline with oral mini pulse (OMP) corticosteroids
      in active vitiligo. METHODS: A total of 50 patients with actively spreading
      vitiligo were randomized to receive either minocycline 100 mg/day (Group I-25
      patients) or OMP 2.5 mg dexamethasone on 2 consecutive days in a week (Group II
      25 patients) for 6 months. These were followed-up at every 2 weeks interval. Mean
      vitiligo disease activity score (VIDA) and mean Vitiligo Area Scoring Index
      (VASI) were assessed in all patients in addition to the photographic comparison
      before and after treatment. RESULTS: Both groups showed a significant decrease in
      VIDA from 4.0 to 1.64+/-0.86 (P<0.001) in Group I and from 4.0 to 1.68+/-0.69
      (P<0.001) in Group II. However, the difference between the mean VIDA scores in
      the two groups was not statistically significant (P=0.60) at the end of treatment
      period. The mean VASI declined from 1.71+/-1.45 to 1.52+/-1.43 Group I (P=0.06)
      and from 1.39+/-1.31 to 1.17+/-1.34 in Group II (P=0.05). The difference between
      VASI in Group I and II was not significant at the end of 24 weeks of treatment
      (P=0.11). CONCLUSION: Both dexamethasone OMP and oral minocycline are effective
      drugs for managing the arrest of disease activity in vitiligo.

PMID- 24448121
TI  - The efficacy of azithromycin in pityriasis rosea: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Macrolides are prescribed in the treatment of pityriasis rosea
      despite conflicting results of the limited number of studies evaluating their
      role in its treatment. AIM: A randomized double-blind placebo-controlled trial
      was conducted to evaluate the effect of azithromycin on the clinical course of
      pityriasis rosea. METHODS: Seventy patients of pityriasis rosea were given either
      azithromycin (n=35) or placebo (n=35) and were followed-up at 2, 4 and 6 weeks.
      Pruritus was assessed in both groups using the visual analogue scale (VAS) .
      Change in the pityriasis rosea severity score (PRSS) and in the VAS were recorded
      as outcome measures and were compared statistically. RESULTS: The decrease in
      PRSS from baseline through 2, 4 and 6 weeks within both treatment (P<0.001) and
      placebo (P<0.001) arms was found to be statistically significant; however, this
      change was not significantly different in the two groups (P=0.179). Similarly,
      the decrease in VAS was found to be statistically significant within both groups
      (P<0.001); however, the change was comparable between the two groups (P<0.937).
      Analysis by Fisher's exact test did not find a significant difference between the
      two groups for PRSS and VAS. CONCLUSION: Azithromycin is not effective in
      pityriasis rosea and the use of macrolides for this disease should not be
      encouraged in clinical practice.

PMID- 24448122
TI  - Removal of corns by punch incision: a retrospective analysis of 15 patients.
AB  - BACKGROUND: Hard corns are firm, small, dome-shaped papules with translucent
      central cores, which occur on the palmoplantar region of toes and hands due to
      repeated trauma. Medical management of hard corns is difficult and sometimes
      requires surgical excision. Punch incision is a technique which is performed
      using a circular blade or trephine attached to a pencil-like handle. AIM: We
      hypothesized that it might serve as an alternative method to surgical excision in
      the treatment of recalcitrant corns and performed the technique to treat 17 corns
      in 15 patients. The present study aimed to review these 15 patients
      retrospectively and evaluate the effectiveness of punch incision. METHOD: A total
      of 15 patients with recalcitrant corns were treated using punch incision between
      April 2011 and December 2012 and were evaluated by photographs and patient
      satisfaction questionnaires. RESULTS: Out of the 17 corns, 3 corns persisted
      after punch incision and the patients were referred to the orthopedic clinic for
      further treatment; 2 of the 17 corns partially responded and required additional
      topical treatment; and 12 of the 17 corns responded completely to punch incision.
      CONCLUSION: Punch incision is a simple and effective technique for the treatment
      of small corns on the palms and soles.

PMID- 24448123
TI  - A t(r)icky mole behind the ear.

PMID- 24448124
TI  - IgG/IgA pemphigus reactive with desmoglein 1 with additional undetermined
      reactivity with epidermal basement membrane zone.
AB  - IgG/IgA pemphigus is an extremely rare subset of pemphigus, showing anti
      keratinocyte cell surface antibodies of both IgG and IgA classes. Herein, we
      describe a unique case of IgG/IgA pemphigus with clinical features of edematous
      erythema and peripheral vesiculopustules. Histopathology showed the presence of
      subcorneal pustules and acantholytic blisters in the mid-epidermis with
      neutrophilic infiltration and eosinophilic spongiosis. Direct immunofluorescence
      of perilesional skin showed both IgG and IgA deposits to keratinocyte cell
      surfaces and unusual granular deposits of IgG, IgM, and C3 along basement
      membrane zone. On enzyme linked immunosorbent assay , the auto-antibodies were
      found to be reactive to desmoglein 1 antigen. Various clinical,
      histopathological, and immunological findings in our case overlapped with the
      features of IgA pemphigus, pemphigus herpetiformis, and pemphigus foliaceus.
      These findings indicate that IgG/IgA pemphigus may be a transitional form between
      IgA pemphigus and pemphigus herpetiformis, and thus provides insight into the
      pathogenicity of this rare disorder. 

PMID- 24448125
TI  - Sturge-Weber syndrome in association with Klippel-Trenaunay syndrome and
      phakomatosis pigmentovascularis type IIb.
AB  - Phakomatosis pigmentovascularis (PPV) is a rare combination of pigmentary and
      vascular components with or without systemic involvement. We report here a rare
      association of Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and PPV type
      IIb in a 15-year-old boy who had right upper limb monoparesis along with a
      history of recurrent convulsions. 

PMID- 24448126
TI  - Trichorhinophalangeal syndrome type I--clinical, microscopic, and molecular
      features.
AB  - Trichorhinophalangeal syndrome type I (TRPS I) is an autosomal dominant
      malformation syndrome characterized by a triad of hair alteration, craniofacial
      and skeletal abnormalities. TRPS1 gene was first identified in 2000 and mapped on
      chromosome 8q23.3. A 39-year-old female patient with short stature (149 cm)
      visited for fine sparse and slow-growing hair with receded medio-occipital
      hairline of roughly triangular shape since infancy. A typical pear-shaped nose
      and elongated philtrum were noticeable. In addition, she reported deviation of
      middle phalanges, bilateral coxa varus in both hips and brachydactyly on
      bilateral fourth digits. Mutation analysis identified a transition of cytosine to
      thymine at position 1630 (exon 4), which results in amino acid change R544X and a
      premature stop of translation. There is no established treatment. But through
      careful evaluation of suspicious cases to identify potential mutation carriers,
      the patient can receive information about the disease and genetic counseling. 

PMID- 24448127
TI  - Informed consent in dermatology: what's known and what's new?

PMID- 24448128
TI  - Contact allergens in Kashmiri population: results from a 6-year patch testing
      experience in 550 patients.

PMID- 24448129
TI  - Long-term prognosis of pemphigus in central Kerala, India: a retrospective cohort
      study.

PMID- 24448130
TI  - Fatal newborn varicella despite varicella zoster immunoglobulin prophylaxis.

PMID- 24448132
TI  - Spontaneous partial repigmentation of halo nevi around congenital melanocytic
      nevus and vitiligo in a 13-year-old boy.

PMID- 24448131
TI  - A case of ultraviolet B-induced linear IgA bullous dermatosis.

PMID- 24448133
TI  - Pigmentation resembling cross-section of a mitochondrion.

PMID- 24448134
TI  - Happle-Tinschert syndrome: report of a newly delineated entity.

PMID- 24448135
TI  - Squamous cell carcinoma presenting as a giant cutaneous horn of the lower lip.

PMID- 24448136
TI  - Scrofuloderma associated with tuberculosis verrucosa cutis.

PMID- 24448137
TI  - Malassezia associated hyperkeratosis of the nipple in young females: report of
      three cases.

PMID- 24448138
TI  - Bullous pemphigoid presenting as a malar rash.

PMID- 24448139
TI  - Revisiting cutaneous metastasis from carcinoma gall bladder.

PMID- 24448140
TI  - Familial reactive perforating collagenosis in three siblings.

PMID- 24448141
TI  - A case of Frey's syndrome.

PMID- 24448142
TI  - Late onset localized steatocystoma multiplex of the vulva.

PMID- 24448143
TI  - Fixed drug eruption due to modafinil.

PMID- 24448144
TI  - Psoriasiform reactions during treatment with abatacept.

PMID- 24448145
TI  - Imatinib mesylate-induced severe lichenoid rash.

PMID- 24448146
TI  - Thrombophlebitis of the lateral chest wall (Mondor's disease).
AB  - Mondor's disease is a rare condition, which involves the thrombophlebitis of the
      superficial veins of the breast and anterior chest wall. A 37-year-old woman
      presented with sudden onset of local pain and edema on her right chest wall,
      accompanied by a longitudinal retraction of the skin during arm abduction in the
      area. Clinical, histological and ultrasonographic findings confirmed Mondor's
      disease and the treatment was symptomatic, using pain relievers and warm
      compresses. The symptomatology remitted within 2 weeks of therapy. Mondor's
      disease is a rare condition where ultrasound complements the clinical evaluation
      and allows the characterization of certain abnormalities, which correlated with
      functional biochemical data and other procedures may substitute the need of
      biopsy. 

PMID- 24448147
TI  - Facial variant of eruptive vellus hair cyst.

PMID- 24448148
TI  - Nicolau syndrome involving whole ipsilateral limb induced by intramuscular
      administration of gentamycin.

PMID- 24448149
TI  - Giant porokeratosis of Mibelli with squamous cell carcinoma.

PMID- 24448150
TI  - Hair casts.

PMID- 24448151
TI  - Lupus vulgaris in a child: a complication of ear piercing.

PMID- 24448153
TI  - Rituximab therapy for factor II inhibitor in a patient with antiphospholipid
      antibody syndrome.
AB  - Factor II inhibitors have been associated with an increased risk of bleeding. The
      management of patients with factor II inhibitors has not been adequately
      described. We describe a patient with an increased bleeding tendency due to
      factor II inhibitor who was unable to undergo surgery due to her bleeding
      tendency. The patient was successfully treated with a course of rituximab, which
      markedly reduced her factor II inhibitor: the factor II level rose from 12 to
      61%; prothrombin time decreased from 20 to 14.7 s; and partial thromboplastin
      time (PTT) decreased from 148 to 38.8 s. She was able to undergo abdominal
      surgery without any hemorrhagic complications. This case exemplifies the
      possibility of treating patients with factor II inhibitors with rituximab
      therapy. 

PMID- 24448152
TI  - Prostatic ischemia induces ventral prostatic hyperplasia in the SHR; possible
      mechanism of development of BPH.
AB  - In the light of increasing evidence that benign prostatic hyperplasia is
      associated with cardiovascular disease, we have investigated the relationship
      between prostatic blood flow and prostatic hyperplasia in the spontaneously
      hypertensive-rat (SHR). Twelve-week-old male SHRs were treated with nicorandil
      for six weeks. Wistar-Kyoto rats were used as controls. Six weeks after
      nicorandil treatment, blood pressure and the prostatic blood flow were estimated,
      and tissue levels of malondialdehyde, HIF-1alpha, TGF-beta1, bFGF,
      dihydrotestosterone, and alpha-SMA were measured. SHRs showed significant
      increases in blood pressure, tissue levels of malondialdehyde, HIF-1alpha, TGF
      beta1, bFGF, alpha-SMA and a significant decrease in the prostatic blood flow.
      Although treatment with nicorandil failed to alter the blood-pressure and alpha
      SMA, it significantly ameliorated the increased levels of malondialdehyde, HIF
      1alpha, TGF-beta1, and bFGF. There were no significant differences in tissue
      levels of dihydrotestosterone among any groups. These data indicate that
      development of prostatic hyperplasia may be associated with prostatic hypoxia,
      which nicorandil prevents via its effect to increase the blood flow. 

PMID- 24448154
TI  - Genetic polymorphisms and plasma levels of tissue factor and tissue factor
      pathway inhibitor in venous thromboembolism.
AB  - Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) play important
      roles in coagulation. The aim of this study was to investigate the distributions
      of TF and TFPI polymorphisms in Koreans and to analyze the association of these
      genetic polymorphisms with plasma levels and development of venous
      thromboembolism (VTE). The polymorphisms TF 5466 A > G, TF -603 A > G, TFPI -287
      T > C and TFPI -33 T > C were investigated in 40 Korean VTE patients and 40 age
      matched and sex-matched controls by real-time PCR followed by melting curve
      analysis and DNA sequence analysis. Plasma levels of TF and TFPI were measured by
      enzyme-linked immunosorbent assay. The G allele of TF 5466 was not detected, and
      allelic frequencies of TF -603 G, TFPI -287 C and TFPI -33 C were 27.5, 67.5 and
      16.2%, respectively. The distributions of TF and TFPI polymorphisms were not
      different between patients and controls. The presence of TF -603 G allele was
      correlated with low plasma TF levels (P = 0.029). Mean plasma TFPI levels were
      similar between TFPI genotypic groups. Although not statistically significant,
      plasma TF and TFPI levels were higher in patients than controls. The
      distributions of TF and TFPI polymorphisms in Koreans were considerably different
      from whites, suggesting ethnic variations. The TF -603 A > G polymorphism was
      significantly correlated with decreased plasma TF levels. Neither genetic
      polymorphisms in TF and TFPI nor their plasma levels seem to act as direct risk
      factors for VTE.

PMID- 24448156
TI  - Novel thioarsenates {[Mn(2,2'-bipy)2(SCN)][Mn(2,2'-bipy)](As(V)S4)}2 and
      {[Mn(2,2'-bipy)2(SCN)]2[As(III)2(S2)2S2]}: introducing an anionic second ligand
      to modify MnII complex cations of 2,2'-bipyridine.
AB  - Two novel manganese thioarsenates, {[Mn(2,2'-bipy)2(SCN)][Mn(2,2'
      bipy)](As(V)S4)}2 (1, 2,2'-bipy = 2,2'-bipyridine) and {[Mn(2,2'
      bipy)2(SCN)]2[As(III)2(S2)2S2]} (2), containing thiocyanate-modified Mn-2,2'-bipy
      complex cations were synthesized. They feature two terminal [Mn(2,2'
      bipy)2(SCN)](+) complex cations bridged by a polyanion {[Mn(2,2'
      bipy)]2(As(V)S4)2}(2-) for 1 and a cyclic thioarsenate anion (As(III)2S6)(2-) for
      2. In 2, the [As(III)2(S2)2S2](2-) anion can be described as two (As(III)S3)(3-)
      trigonal-pyramids interlinked through S-S bonds. The method to obtain new metal
      complex cations shown here, introducing an anionic second ligand to modify the
      number of coordination sites and the charges of the metal complex cations
      simultaneously, is different from the traditional methods, varying either the TM
      center or the organic ligand or employing mixed neutral organic ligands, and may
      open up a new route for preparing novel chalcogenidometalates. Compounds 1 and 2
      exhibit wide optical gaps of 2.20 and 2.67 eV, respectively, and
      photoluminescence with the emission maxima occurring around 440 nm. Magnetic
      measurements show the presence of antiferromagnetic interactions between Mn(II)
      centers in the two compounds.

PMID- 24448157
TI  - Possibilities for digital clocks in Portuguese are more encouraging than in other
      languages.

PMID- 24448155
TI  - Update on von Willebrand factor multimers: focus on high-molecular-weight
      multimers and their role in hemostasis.
AB  - Normal hemostasis requires von Willebrand factor (VWF) to support platelet
      adhesion and aggregation at sites of vascular injury. VWF is a multimeric
      glycoprotein built from identical subunits that contain binding sites for both
      platelet glycoprotein receptors and collagen. The adhesive activity of VWF
      depends on the size of its multimers, which range from 500 to over 10 000 kDa.
      There is good evidence that the high-molecular-weight multimers (HMWM), which are
      5000-10 000 kDa, are the most effective in supporting interaction with collagen
      and platelet receptors and in facilitating wound healing under conditions of
      shear stress. Thus, these HMWM of VWF are of particular clinical interest. The
      unusually large multimers of VWF are, under normal conditions, cleaved by the
      plasma metalloproteinase ADAMTS13 to smaller, less adhesive multimers. A
      reduction or lack of HMWM, owing to a multimerization defect of VWF or to an
      increased susceptibility of VWF for ADAMTS13, leads to a functionally impaired
      VWF and the particular type 2A of von Willebrand disease. This review considers
      the biology and function of VWF multimers with a particular focus on the
      characterization of HMWM - their production, storage, release, degradation, and
      role in normal physiology. Evidence from basic research and the study of clinical
      diseases and their management highlight a pivotal role for the HMWM of VWF in
      hemostasis. 

PMID- 24448158
TI  - An unprecedented Pd-catalyzed trans-addition of boronic acids to ynamides.
AB  - An unprecedented Pd-catalyzed trans-addition of boronic acids to ynamides has
      been reported, giving alpha,beta-disubstituted enamides in high yields with
      excellent regio- and stereoselectivity. A possible mechanism involving the
      palladium carbene intermediate has been proposed to account for the unusual trans
      addition. 

PMID- 24448159
TI  - CTL induction by DNA vaccine with Toxoplasma gondii-HSP70 gene.
AB  - Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) is a tachyzoite
      specific virulent molecule. The DNA vaccine with T.g.HSP70 gene targeting
      peripheral epidermal or dermal dendritic cells (DC) induces in vivo DC maturation
      and successive early Th1 polarization at the draining lymph nodes (dLN) of
      C57BL/6 mice. In the present study, induction of cytotoxic T lymphocytes (CTL)
      has been explored. The CTL specific for a syngeneic DC line, DC2.4, either
      transfected with T. g.HSP70 gene or pulsed with recombinant T. g.HSP70 are
      induced in the spleen of the vaccinated mice. This CTL lyses T. gondii-infected,
      but not uninfected, DC2.4. Both CD8(+) and CD4(+) CTL are induced by the vaccine,
      and Fas/Fas ligand-mediated cytolysis dominantly participates in their CTL
      activities. Adoptive transfer experiments reveal that the vaccine-induced CD8(+)
      or CD4(+) T cells possess a protective role for toxoplasmosis at both acute and
      chronic phases of infection. 

PMID- 24448160
TI  - Gene therapy using a liver-targeted AAV vector restores nucleoside and nucleotide
      homeostasis in a murine model of MNGIE.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive disorder caused by mutations in TYMP, enconding thymidine phosphorylase
      (TP). TP deficiency results in systemic accumulation of thymidine and
      deoxyuridine, which interferes with mitochondrial DNA (mtDNA) replication and
      leads to mitochondrial dysfunction. To date, the only treatment available for
      MNGIE patients is allogeneic hematopoietic stem cell transplantation, which is
      associated with high morbidity and mortality. Here, we report that AAV2/8
      mediated transfer of the human TYMP coding sequence (hcTYMP) under the control of
      a liver-specific promoter prevents the biochemical imbalances in a murine model
      of MNGIE. hcTYMP expression was restricted to liver, and a dose as low as 2 *
      10(11) genome copies/kg led to a permanent reduction in systemic nucleoside
      levels to normal values in about 50% of treated mice. Higher doses resulted in
      reductions to normal or slightly below normal levels in virtually all mice
      treated. The nucleoside reduction achieved by this treatment prevented
      deoxycytidine triphosphate (dCTP) depletion, which is the limiting factor
      affecting mtDNA replication in this disease. These results demonstrate that the
      use of AAV to direct TYMP expression in liver is feasible as a potentially safe
      gene therapy strategy for MNGIE. 

PMID- 24448161
TI  - A pRb-responsive, RGD-modified, and hyaluronidase-armed canine oncolytic
      adenovirus for application in veterinary oncology.
AB  - Human and canine cancer share similarities such as genetic and molecular aspects,
      biological complexity, tumor epidemiology, and targeted therapeutic treatment.
      Lack of good animal models for human adenovirotherapy has spurred the use of
      canine adenovirus 2-based oncolytic viruses. We have constructed a canine
      oncolytic virus that mimics the characteristics of our previously published human
      adenovirus ICOVIR17: expression of E1a controlled by E2F sites, deletion of the
      pRb-binding site of E1a, insertion of an RGD integrin-binding motif at the fiber
      Knob, and expression of hyaluronidase under the major late promoter/IIIa protein
      splicing acceptor control. Preclinical studies showed selectivity, increased
      cytotoxicity, and strong hyaluronidase activity. Intratumoral treatment of canine
      osteosarcoma and melanoma xenografts in mice resulted in inhibition of tumor
      growth and prolonged survival. Moreover, we treated six dogs with different tumor
      types, including one adenoma, two osteosarcomas, one mastocitoma, one
      fibrosarcoma, and one neuroendocrine hepatic carcinoma. No virus-associated
      adverse effects were observed, but toxicity associated to tumor lysis, including
      disseminated intravascular coagulation and systemic failure, was found in one
      case. Two partial responses and two stable diseases warrant additional clinical
      testing. 

PMID- 24448162
TI  - Proliferation and cilia dynamics in neural stem cells prospectively isolated from
      the SEZ.
AB  - Neural stem cells (NSCs) generate new neurons in vivo and in vitro throughout
      adulthood and therefore are physiologically and clinically relevant. Unveiling
      the mechanisms regulating the lineage progression from NSCs to newborn neurons is
      critical for the transition from basic research to clinical application. However,
      the direct analysis of NSCs and their progeny is still elusive due to the
      problematic identification of the cells. We here describe the isolation of highly
      purified genetically unaltered NSCs and transit-amplifying precursors (TAPs) from
      the adult subependymal zone (SEZ). Using this approach we show that a primary
      cilium and high levels of epidermal growth factor receptor (EGFR) at the cell
      membrane characterize quiescent and cycling NSCs, respectively. However, we also
      observed non-ciliated quiescent NSCs and NSCs progressing into the cell cycle
      without up-regulating EGFR expression. Thus, the existence of NSCs displaying
      distinct molecular and structural conformations provides more flexibility to the
      regulation of quiescence and cell cycle progression. 

PMID- 24448163
TI  - Comparison of the effects of retroviral restriction factors involved in
      resistance to porcine endogenous retrovirus.
AB  - Three major classes of retroviral restriction factors (APOBEC3G, Tetherin, and
      TRIM5alpha) have been identified in mammals. Restriction factors are cellular
      proteins that are able to limit viral replication by targeting specific steps of
      the viral life cycle. To evaluate which restriction factor is the most effective
      to inhibit the replication of porcine endogenous retroviruses (PERVs), the
      antiviral activity of each restriction factor was compared. In pseudotype assay,
      the antiviral activity of human tetherin against PERV pseudotype was slightly
      weaker than that of human APOBEC3G (hA3G). A combination of tetherin and hA3G was
      more potent than each individual restriction factor. We questioned whether a
      combination of tetherin and hA3G could also inhibit the spreading replication of
      PERV. In agreement with the pseudotype assay, two restriction factors inhibit
      infectious PERV replication in a spreading infection. In this study, hA3G could
      strongly inhibit the replication of PERV, but tetherin modestly restricted it.
      Based on these results, we concluded that a combination of tetherin and hA3G is
      the most effective way to restrict PERV. A combination of different restriction
      factors will encourage the development of a new approach to treat retroviral
      disease.

PMID- 24448164
TI  - Comparison of two laccases from Trametes versicolor for application in the
      decolorization of dyes.
AB  - It has been previously demonstrated that laccases exhibit great potential for use
      in several industrial and environmental applications. In this paper, two laccase
      isoenzyme genes, lccB and lccC, were cloned and expressed in Pichia pastoris
      GS115. The sequence analysis indicated that the lccB and lccC genes consisted of
      1,563 and 1,584 bp, and their open reading frames encoded 520 and 527 amino
      acids, respectively. They had 72.7% degree of identity in nucleotides and 86.7%
      in amino acids. The expression levels of LccB and LccC were up to 32,479 and
      34,231 U/l, respectively. The recombinant laccases were purified by
      ultrafiltration and (NH4)2SO4 precipitation, showing a single band on SDS-PAGE,
      which had a molecular mass of 58 kDa. The optimal pH and temperature for LccB
      were 2.0 and 55 degrees C with 2,2'-azino-bis-[3-ethylbenzthiazolinesulfonic acid
      (ABTS) as a substrate, whereas LccC exhibited optimal pH and temperature at 3.0
      and 60 degrees C. The apparent kinetic parameters of LccB were 0.43 mM for ABTS
      with a Vmax value of 51.28 U/mg, and the Km and Vmax values for LccC were 0.29 mM
      and 62.89 U/mg. The recombinant laccases were able to decolorize five types of
      dyes. Acid Violet 43 (100 g/ml) was completely decolorized by LccB or LccC (2
      U/ml), and the decolorization of Reactive Blue KN-R (100 g/ml) was 91.6% by LccC
      (2 U/ml). Thus, the study characterizes useful laccase isoenzymes from T.
      versicolor that have the capability of being incorporated into the treatment of
      similar azo and anthraquinone dyes from dyeing industries.

PMID- 24448165
TI  - Effects of microbial iron reduction and oxidation on the immobilization and
      mobilization of copper in synthesized Fe(III) minerals and Fe-rich soils.
AB  - The effects of microbial iron reduction and oxidation on the immobilization and
      mobilization of copper were investigated in a high concentration of sulfate with
      synthesized Fe(III) minerals and red earth soils rich in amorphous Fe
      (hydr)oxides. Batch microcosm experiments showed that red earth soil inoculated
      with subsurface sediments had a faster Fe(III) bioreduction rate than pure
      amorphous Fe(III) minerals and resulted in quicker immobilization of Cu in the
      aqueous fraction. Coinciding with the decrease of aqueous Cu, SO4(2-) in the
      inoculated red earth soil decreased acutely after incubation. The shift in the
      microbial community composite in the inoculated soil was analyzed through
      denaturing gradient gel electrophoresis. Results revealed the potential
      cooperative effect of microbial Fe(III) reduction and sulfate reduction on copper
      immobilization. After exposure to air for 144 h, more than 50% of the immobilized
      Cu was remobilized from the anaerobic matrices; aqueous sulfate increased
      significantly. Sequential extraction analysis demonstrated that the organic
      matter/sulfide-bound Cu increased by 52% after anaerobic incubation relative to
      the abiotic treatment but decreased by 32% after oxidation, indicating the
      generation and oxidation of Cu-sulfide coprecipitates in the inoculated red earth
      soil. These findings suggest that the immobilization of copper could be enhanced
      by mediating microbial Fe(III) reduction with sulfate reduction under anaerobic
      conditions. The findings have an important implication for bioremediation in
      Cucontaminated and Fe-rich soils, especially in acid-mine-drainage-affected
      sites.

PMID- 24448166
TI  - Purification and characterization of a thermostable xylanase from Paenibacillus
      sp. NF1 and its application in xylooligosaccharides production.
AB  - High levels of extracellular xylanase activity (211.79 IU/mg) produced by
      Paenibacillus sp. NF1 were detected when it was submerged-cultured. After three
      consecutive purification steps using Octyl-Sepharose, Sephadex G75, and Q
      Sepharose columns, a thermostable xylanase (XynNF) was purified to homogeneity
      and showed a molecular mass of 37 kDa according to SDS-PAGE. The specific
      activity of the purified XynNF was up to 3,081.05 IU/mg with a 14.55-fold
      purification. The activity of XynNF was stimulated by Ca(2+), Ba(2+), DTT, and
      beta-mercaptoethanol, but was inhibited by Fe(3+), Zn(2+), Fe(2+), Cu(2+), SDS,
      and EDTA. The purified XynNF displayed a greater affinity for oat spelt xylan
      with the maximal enzymatic activity at 60 degrees C and pH 6.0. XynNF, which was
      shown to be cellulose-free, with high stability at high temperature (70 degrees C
      80 degrees C) and low pH range (pH 4.0-7.0), is potentially valuable for various
      industrial applications. The end products of high efficient oat spelt xylan
      hydrolysis by XynNF (an endoxylanase) containing 95.8% xylooligosaccharides of 2
      4 degree of polymerization (DP2-4) with the enrichment of xylobiose (61.5%)
      indicated that XynNF is a promising candidate for xylooligosaccharides
      production.

PMID- 24448167
TI  - The control of tendon-driven dexterous hands with joint simulation.
AB  - An adaptive impedance control algorithm for tendon-driven dexterous hands is
      presented. The main idea of this algorithm is to compensate the output of the
      classical impedance control by an offset that is a proportion-integration
      differentiation (PID) expression of force error. The adaptive impedance control
      can adjust the impedance parameters indirectly when the environment position and
      stiffness are uncertain. In addition, the position controller and inverse
      kinematics solver are specially designed for the tendon-driven hand. The
      performance of the proposed control algorithm is validated by using MATLAB and
      ADAMS software for joint simulation. ADAMS is a great software for virtual
      prototype analysis. A tendon-driven hand model is built and a control module is
      generated in ADAMS. Then the control system is built in MATLAB using the control
      module. The joint simulation results demonstrate fast response and robustness of
      the algorithm when the environment is not exactly known, so the algorithm is
      suitable for the control of tendon-driven dexterous hands. 

PMID- 24448168
TI  - Modeling and characterization of the implant intra-body communication based on
      capacitive coupling using a transfer function method.
AB  - Implantable devices have important applications in biomedical sensor networks
      used for biomedical monitoring, diagnosis and treatment, etc. In this paper, an
      implant intra-body communication (IBC) method based on capacitive coupling has
      been proposed, and the modeling and characterization of this kind of IBC has been
      investigated. Firstly, the transfer function of the implant IBC based on
      capacitive coupling was derived. Secondly, the corresponding parameters of the
      transfer function are discussed. Finally, both measurements and simulations based
      on the proposed transfer function were carried out, while some important
      conclusions have been achieved, which indicate that the achieved transfer
      function and conclusions are able to help to achieve an implant communication
      method with the highly desirable characteristics of low power consumption, high
      data rate, high transmission quality, etc. 

PMID- 24448169
TI  - Two-stage system based on a software-defined radio for stabilizing of optical
      frequency combs in long-term experiments.
AB  - A passive optical resonator is a special sensor used for measurement of lengths
      on the nanometer and sub-nanometer scale. A stabilized optical frequency comb can
      provide an ultimate reference for measuring the wavelength of a tunable laser
      locked to the optical resonator. If we lock the repetition and offset frequencies
      of the comb to a high-grade radiofrequency (RF) oscillator its relative frequency
      stability is transferred from the RF to the optical frequency domain. Experiments
      in the field of precise length metrology of low-expansion materials are usually
      of long-term nature so it is required that the optical frequency comb stay in
      operation for an extended period of time. The optoelectronic closed-loop systems
      used for stabilization of combs are usually based on traditional analog
      electronic circuits processing signals from photodetectors. From an experimental
      point of view, these setups are very complicated and sensitive to ambient
      conditions, especially in the optical part, therefore maintaining long-time
      operation is not easy. The research presented in this paper deals with a novel
      approach based on digital signal processing and a software-defined radio. We
      describe digital signal processing algorithms intended for keeping the
      femtosecond optical comb in a long-time stable operation. This need arose during
      specialized experiments involving measurements of optical frequencies of tunable
      continuous-wave lasers. The resulting system is capable of keeping the comb in
      lock for an extensive period of time (8 days or more) with the relative stability
      better than 1.6 * 10(-11).

PMID- 24448170
TI  - Estimating the concentration and biodegradability of organic matter in 22
      wastewater treatment plants using fluorescence excitation emission matrices and
      parallel factor analysis.
AB  - This study aimed at monitoring the changes of fluorescent components in
      wastewater samples from 22 Korean biological wastewater treatment plants and
      exploring their prediction capabilities for total organic carbon (TOC), dissolved
      organic carbon (DOC), biochemical oxygen demand (BOD), chemical oxygen demand
      (COD), and the biodegradability of the wastewater using an optical sensing
      technique based on fluorescence excitation emission matrices and parallel factor
      analysis (EEM-PARAFAC). Three fluorescent components were identified from the
      samples by using EEM-PARAFAC, including protein-like (C1), fulvic-like (C2) and
      humic-like (C3) components. C1 showed the highest removal efficiencies for all
      the treatment types investigated here (69% +/- 26%-81% +/- 8%), followed by C2
      (37% +/- 27%-65% +/- 35%), while humic-like component (i.e., C3) tended to be
      accumulated during the biological treatment processes. The percentage of C1 in
      total fluorescence (%C1) decreased from 54% +/- 8% in the influents to 28% +/- 8%
      in the effluents, while those of C2 and C3 (%C2 and %C3) increased from 43% +/-
      6% to 62% +/- 9% and from 3% +/- 7% to 10% +/- 8%, respectively. The
      concentrations of TOC, DOC, BOD, and COD were the most correlated with the
      fluorescence intensity (Fmax) of C1 (r = 0.790-0.817), as compared with the other
      two fluorescent components. The prediction capability of C1 for TOC, BOD, and COD
      were improved by using multiple regression based on Fmax of C1 and suspended
      solids (SS) (r = 0.856-0.865), both of which can be easily monitored in situ. The
      biodegradability of organic matter in BOD/COD were significantly correlated with
      each PARAFAC component and their combinations (r = -0.598-0.613, p < 0.001), with
      the highest correlation coefficient shown for %C1. The estimation capability was
      further enhanced by using multiple regressions based on %C1, %C2 and C3/C2 (r = 
      0.691). 

PMID- 24448171
TI  - Optical properties of a vibrationally modulated solid state Mott insulator.
AB  - Optical pulses at THz and mid-infrared frequencies tuned to specific vibrational
      resonances modulate the lattice along chosen normal mode coordinates. In this
      way, solids can be switched between competing electronic phases and new states
      are created. Here, we use vibrational modulation to make electronic interactions
      (Hubbard-U) in Mott-insulator time dependent. Mid-infrared optical pulses excite
      localized molecular vibrations in ET-F2TCNQ, a prototypical one-dimensional Mott
      insulator. A broadband ultrafast probe interrogates the resulting optical
      spectrum between THz and visible frequencies. A red-shifted charge-transfer
      resonance is observed, consistent with a time-averaged reduction of the
      electronic correlation strength U. Secondly, a sideband manifold inside of the
      Mott-gap appears, resulting from a periodically modulated U. The response is
      compared to computations based on a quantum-modulated dynamic Hubbard model.
      Heuristic fitting suggests asymmetric holon-doublon coupling to the molecules and
      that electron double-occupancies strongly squeeze the vibrational mode. 

PMID- 24448172
TI  - Storage of serum peptide information in nanoporous silicon microparticles.
AB  - Serum peptides are becoming a rich source of disease biomarkers, therefore,
      preserving serum peptide information after sample collection is of great
      importance. This work demonstrates that nanoporous silicon microparticles can be
      successfully applied in the storage of peptide information. 

PMID- 24448173
TI  - Correlations between serum uric acid and coronary atherosclerosis before and
      during statin therapy.
AB  - OBJECTIVE: The role of serum uric acid (UA) in the pathophysiology of
      atherosclerosis is ambiguous and remains controversial. The purpose of the
      present study was to evaluate the relationship between serum UA and coronary
      atherosclerosis. PATIENTS AND METHODS: Coronary atherosclerosis in the nonculprit
      lesions was evaluated using virtual histology intravascular ultrasound in 119
      patients with angina pectoris at the time of percutaneous coronary intervention
      and 8 months after statin therapy. RESULTS: Serum UA levels showed weak but
      significant positive correlations with external elastic membrane volume
      (baseline: r=0.236, P=0.02; 8-month follow-up: r=0.307, P=0.0009) and with plaque
      volume (baseline: r=0.263, P=0.007; 8-month follow-up: r=0.349, P=0.0001).
      Significant decreases in the fibrofatty and fibrous components and increases in
      the necrotic core and dense calcium components were observed during statin
      therapy. Serum UA (r=0.257, P=0.009) and unstable angina pectoris (r=0.208,
      P=0.02) correlated significantly with change in the calcified plaque volume,
      whereas the estimated glomerular filtration rate trended (r=-0.166, P=0.07).
      Multivariate regression analyses showed that UA was a significant independent
      predictor associated with an increase in the dense calcium plaque volume during
      statin therapy (beta=0.244, P=0.03). CONCLUSION: In this preliminary study, serum
      UA levels correlated with coronary atherosclerosis before and during statin
      therapy. It remains unknown whether these correlations are a direct effect of UA
      itself or a marker of increased risk.

PMID- 24448174
TI  - TNF-alpha production in NKT cell hybridoma is regulated by sphingosine-1
      phosphate: implications for inflammation in atherosclerosis.
AB  - OBJECTIVES: Natural killer T (NKT) cells are unique T lymphocytes that recognize
      glycolipid antigen and produce various cytokines. NKT cells accelerate
      atherosclerosis in mice. Sphingosine-1-phosphate (S1P) is a bioactive
      sphingolipid and regulates T-lymphocyte trafficking. We aimed to determine the
      effects of S1P on the production of proinflammatory cytokine, tumor necrosis
      factor (TNF)-alpha, in NKT cell hybridomas and mouse NKT cells. MATERIALS AND
      METHODS: NKT cell hybridomas and sorted mouse NKT cells were stimulated with S1P
      and alpha-galactosylceramide (alpha-GalCer), the major ligand to produce
      cytokines in NKT cells. TNF-alpha mRNA expression and protein production were
      determined by real-time PCR and ELISA, respectively. Cell migration was assayed
      using chemotaxicell. Plasma S1P was measured using HPLC. RESULTS: Hybridomas
      expressed S1P receptors, S1P1, S1P2, and S1P4. S1P and alpha-GalCer increased TNF
      alpha mRNA expression and protein production. S1P enhanced TNF-alpha induction by
      alpha-GalCer. S1P receptor antagonists decreased the TNF-alpha mRNA expression
      induced by S1P. FTY720, an immunosuppressive S1P receptor modulator, also
      decreased the TNF-alpha mRNA expression. The migration of NKT cell hybridomas was
      increased by S1P. FTY720 reduced the migration induced by S1P. S1P also increased
      the TNF-alpha mRNA expression in mouse NKT cells. Plasma TNF-alpha levels in
      patients with high plasma S1P (>=500 nmol/l) were higher than those in patients
      with low S1P (<500 nmol/l). CONCLUSION: S1P binds to S1P receptors in NKT cells
      and enhances TNF-alpha production. TNF-alpha overproduction may induce
      atherogenic inflammatory responses. S1P may serve as a novel therapeutic target
      for amelioration of vascular inflammatory diseases.

PMID- 24448175
TI  - Effect of tetracaine on DMPC and DMPC+cholesterol biomembrane models: liposomes
      and monolayers.
AB  - Different types of lipid bilayers/monolayers have been used to simulate the
      cellular membranes in the investigation of the interactions between drugs and
      cells. However, to our knowledge, very few studies focused on the influence of
      the chosen membrane model upon the obtained results. The main objective of this
      work is to understand how do the nature and immobilization state of the
      biomembrane models influence the action of the local anaesthetic tetracaine (TTC)
      upon the lipid membranes. The interaction of TTC with different biomembrane
      models of dimyristoylphosphatidylcholine (DMPC) with and without cholesterol
      (CHOL) was investigated through several techniques. A quartz crystal microbalance
      with dissipation (QCM-D) was used to study the effect on immobilized liposomes,
      while phosphorus nuclear magnetic resonance ((31)P-NMR) and differential scanning
      calorimetry (DSC) were applied to liposomes in suspension. The effect of TTC on
      Langmuir monolayers of lipids was also investigated through surface pressure-area
      measurements at the air-water interface. The general conclusion was that TTC has
      a fluidizing effect on the lipid membranes and, above certain concentrations,
      induces membrane swelling or even solubilization. However, different models led
      to variable responses to the TTC action. The intensity of the disordering effect
      caused by TTC increased in the following order: supported liposomes<liposomes in
      solution<Langmuir monolayers. This means that extrapolation of the results
      obtained in in vitro studies of the lipid/anaesthetic interactions to in vivo
      conditions should be done carefully. 

PMID- 24448176
TI  - Composition and properties of the surface of oil bodies recovered from Echium
      plantagineum.
AB  - Neutral-lipids within oilseeds are most commonly stored in oil bodies, small
      spherical organelles with oleosin proteins inserted through a phospholipid
      monolayer. Oil bodies extracted from Echium plantagineum are highly enriched in
      polyunsaturated fatty acids and are stable to coalescence and oxidation. This
      stability has been attributed to the strong association between the phospholipid
      monolayer and oleosin proteins. To better understand this association the
      phospholipid fatty acyl groups of E. Plantagineum oil bodies were determined for
      the first time; a large proportion (~70%) of saturated fatty acids were present,
      and this may aid in oleosin anchorage and thus contributes to oil body stability.
      The effect of oil body washing on surface charge was also observed (using
      turbidity, zeta and streaming potentials), and dependent on the washing protocol,
      E. Plantagineum oil bodies had an isoelectric point of pH 4-5. This is
      significantly different to pI values for oil bodies from a range of other seeds
      reported in the literature using isoelectric focusing; a possible explanation for
      this discrepancy is discussed.

PMID- 24448177
TI  - Honokiol nanosuspensions: preparation, increased oral bioavailability and
      dramatically enhanced biodistribution in the cardio-cerebro-vascular system.
AB  - Honokiol is a phytochemical component with multiple pharmacological activities,
      but Honokiol's wider use has been restricted by its poor solubility. Using bovine
      serum albumin and polyvinylpyrrolidone as stabilisers in a solvent precipitation
      ultrasonication method, Honokiol nanosuspensions were prepared with a mean
      particle size of 116.2 nm (+/-2 nm), a zeta potential of -44.7 mV (+/-1.7 mV) and
      a high drug payload of 50.4 +/- 0.6% (w/w). X-ray powder diffraction and
      differential scanning calorimetry indicated that Honokiol was in an amorphous
      state in the nanosuspensions, in contrast with bulk Honokiol powder. Honokiol was
      released faster in vitro from nanosuspensions with no burst release, and the
      highest 98% cumulative release was after 60 h. Honokiol nanosuspensions improved
      the oral bioavailability of Honokiol in in vivo studies in rats with a 3.94-fold
      Cmax and a 2.2-fold AUC(0-t). Remarkably, in contrast to oral administration,
      intraperitoneal administration of Honokiol nanosuspensions could dramatically
      alter the biodistribution of Honokiol, resulting in a much higher drug level and
      tissue bioavailability in the blood, heart and brain, benefitting the treatment
      of cardio-cerebro-vascular diseases.

PMID- 24448178
TI  - Intraobserver and interobserver agreement in visual inspection for xanthochromia:
      implications for subarachnoid hemorrhage diagnosis, computed tomography
      validation studies, and the Walton rule.
AB  - BACKGROUND: Visual inspection for xanthochromia is used to diagnose subarachnoid
      hemorrhage (SAH), to validate computed tomography subarachnoid hemorrhage
      diagnosis and was used to determine the Walton rule. No study has assessed the
      reliability of xanthochromia. OBJECTIVE: To determine intraobserver and
      interobserver xanthochromia agreement. METHODS: Mock cerebrospinal fluid samples
      contained increasing concentrations of human oxyhemoglobin, bilirubin, and
      albumin. Non-color-blind observers randomly assessed samples against a white
      background twice under significantly differing illumination. Specimens were
      recorded as red, orange, yellow, or clear. RESULTS: Results were obtained for 26
      observers (11 male, 15 female observers). We found that 19.2% of samples were
      misclassified: red, 11.7%; orange, 28.5%; yellow, 29.6%; and clear, 22.1% (chi =
      213.2; P < .001). Of the yellow misclassifications, 88% were misclassified as
      clear. Female observers correctly classified samples significantly more
      frequently than male observers (P = .03). Intraobserver agreement differed
      significantly from expected for both male (chi = 105.6; P < .001) and female (chi
      = 99.9; P < .001) observers regardless of illumination. Interobserver agreement
      was poor regardless of sex (chi for male observers = 176.96, P < .001; chi for
      female observers = 182.69, P < .001) or illumination (chi for bright = 125.64, P
      < .001; chi for dark = 148.48, P < .001). Overall, there was 75% agreement in 46%
      of the tests and 90% agreement in only 36% of the tests. CONCLUSION: This simple
      laboratory study would be expected to maximize agreement relative to clinical
      practice. Although non-color-blind female observers significantly outperformed
      non-color-blind male observers, both intraobserver agreement and interobserver
      agreement for xanthochromia were prohibitively poor regardless of sex or
      illumination. Yellow was most frequently misclassified, 88% as clear (ie, true
      positives were commuted to false negatives). Xanthochromia is therefore highly
      unreliable for subarachnoid hemorrhage diagnosis and computed tomography
      validation. The Walton rule requires urgent clinical revalidation.

PMID- 24448179
TI  - The dentate nucleus and its projection system in the human cerebellum: the
      dentate nucleus microsurgical anatomical study.
AB  - BACKGROUND: Neurosurgical management of cerebellar lesions remains challenging.
      Thus, it is important to have sound knowledge of the microsurgical anatomy of the
      cerebellum and dentate nucleus (DN) and to define different types of exposure in
      a variety of surgical interventions. OBJECTIVE: To examine the anatomy of the DN
      from a neurosurgical viewpoint using fiber tracking techniques. METHODS: Ten
      formalin-fixed human hemispheres were dissected with the Ludwig and Klingler
      fiber dissection technique under * 6 to * 40 magnification. Anatomic images were
      created with 3-dimensional diffusion tensor imaging. The relationships of the DN
      to tentorium and suboccipital and lateral surfaces of the cerebellum and its
      spatial positioning relative to different surgical approaches in the cerebellum
      and fourth ventricle were examined. The fiber tracts terminating at and
      surrounding the DN were defined. RESULTS: The DN is at greater risk of being
      injured in the transvermian and supratonsillar approaches to the cerebellum and
      fourth ventricle, with lesser risk in the telovelar and subtonsillar approaches.
      Superior approaches are safer compared with other approaches. CONCLUSION: The DN
      represents an important anatomic structure in surgical interventions involving
      the posterior fossa, particularly in the elderly because of the common occurrence
      of atrophy-related problems in this age group. Functionally and anatomically, the
      DN is closely related to the superior and middle cerebellar peduncles. The
      inferior cerebellar peduncle poses positional risks because it follows an
      anterior and superior course relative to the DN. The telovelar approach is a
      safer procedure for interventions involving the pathological lesions of the
      fourth ventricle floor.

PMID- 24448180
TI  - Robot-assisted stereotactic laser ablation in medically intractable epilepsy:
      operative technique.
AB  - BACKGROUND: Stereotactic laser ablation offers an advantage over open surgical
      procedures for treatment of epileptic foci, tumors, and other brain pathology.
      Robot-assisted stereotactic laser ablation could offer an accurate, efficient,
      minimally invasive, and safe method for placement of an ablation catheter into
      the target. OBJECTIVE: To determine the feasibility of placement of a
      stereotactic laser ablation catheter into a brain lesion with the use of robotic
      assistance, via a safe, accurate, efficient, and minimally invasive manner.
      METHODS: A laser ablation catheter (Visualase, Inc) was placed by using robotic
      guidance (ROSA, Medtech Surgical, Inc) under general anesthesia into a localized
      epileptogenic periventricular heterotopic lesion in a 19-year-old woman with 10
      year refractory focal seizure history. The laser applicator (1.65 mm diameter)
      position was confirmed by using magnetic resonance imaging (MRI). Ablation using
      the Visualase system was performed under multiplanar imaging with real-time
      thermal imaging and treatment estimates in each plane. A postablation MRI
      sequence (T1 postgadolinium contrast injection) was used to immediately confirm
      the ablation. RESULTS: MRI showed accurate skin entry point and trajectory, with
      the applicator advanced to the lesion's distal boundary. Ablation was
      accomplished in less than 3 minutes of heating. The overall procedure, from time
      of skin incision to end of last ablation, was approximately 90 minutes. After
      confirmation of proper lesioning by using a T1 contrast-enhanced MRI, the
      applicator was removed, and the incision was closed using a single stitch. No
      hemorrhage or other untoward complication was visualized. The patient awoke
      without any complication, was observed overnight after admitting to a regular
      floor bed, and was discharged to home the following day. CONCLUSION: This
      technique, using a combination of Visualase laser ablation, ROSA robot, and
      intraoperative MRI, facilitated a safe, efficacious, efficient, and minimally
      invasive approach that could be used for placement of 1 or multiple electrodes in
      the future.

PMID- 24448181
TI  - Multitract orthogonal microelectrode localization of the subthalamic nucleus:
      description of a novel technique.
AB  - BACKGROUND: Microelectrode recording helps surgeons accurately localize
      boundaries of the subthalamic nucleus (STN) and surrounding structures in deep
      brain stimulation. OBJECTIVE: To describe a novel adaptation of the Ben gun
      device to optimize efficient mapping. METHODS: Patients who underwent STN deep
      brain stimulation over a 3-year period were reviewed. For the final year, the Ben
      gun was rotated 45 degrees  and the target was offset 1.4 mm lateral and anterior
      in the plane orthogonal to the intended trajectory to allow for simultaneous
      parallel tracks at target, 2.8 mm anterior (localizing the front of STN), and 2.8
      mm lateral (identifying the internal capsule). Before this step, the initial pass
      consisted of 1 to 2 tracks with the frame center targeted to STN. The primary
      outcome measure was the number of passes required for accurate localization of
      the nucleus and boundaries. RESULTS: Eighty-three electrodes were implanted in 45
      patients (mean age, 62; range, 37-78 years), of which 29 electrodes were placed
      by the use of the new technique. One electrode (4%) required more than 1 pass
      using the new technique compared with 36 (67%) using the older technique (P <
      .01). The distance from original target to final electrode position increased
      from 0.67 +/- 0.13 mm to 1.06 +/- 0.15 mm (P < .05) with a greater tendency to
      move the final electrode position posteriorly. There was no statistically
      significant difference in benefit from neurostimulation. CONCLUSION: This
      technique facilitates reliable localization of the STN with fewer passes,
      possibly decreasing the risks associated with more passes and longer duration of
      surgery.

PMID- 24448182
TI  - Dorsal column mapping via phase reversal method: the refined technique and
      clinical applications.
AB  - BACKGROUND: Safe resection of intramedullary spinal cord tumors can be
      challenging, because they often alter the cord anatomy. Identification of
      neurophysiologically viable dorsal columns (DCs) and of neurophysiologically
      inert tissue, eg, median raphe (MR), as a safe incision site is crucial for
      avoiding postoperative neurological deficits. We present our experience with and
      improvements made to our previously described technique of DC mapping,
      successfully applied in a series of 12 cases. OBJECTIVE: To describe a new, safe,
      and reliable technique for intraoperative DC mapping. METHODS: The right and left
      DCs were stimulated by using a bipolar electric stimulator and the triggered
      somatosensory evoked potentials recorded from the scalp. Phase reversal and
      amplitude changes of somatosensory evoked potentials were used to
      neurophysiologically identify the laterality of DCs, the inert MR, as well as
      other safe incision sites. RESULTS: The MR location was neurophysiologically
      confirmed in all patients in whom this structure was first visually identified as
      well as in those in whom it was not, with 1 exception. DCs were identified in all
      patients, regardless of whether they could be visually identified. In 3 cases,
      negative mapping with the use of this method enabled the surgeon to reliably
      identify additional inert tissue for incision. None of the patients had
      postoperative worsening of the DC function. CONCLUSION: Our revised technique is
      safe and reliable, and it can be easily incorporated into routine intramedullary
      spinal cord tumor resection. It provides crucial information to the neurosurgeon
      to prevent postoperative neurological deficits.

PMID- 24448184
TI  - Microsurgical management of giant (>5 cm) internal carotid artery bifurcation
      aneurysms presenting with brainstem compression using radial artery interposition
      bypass graft: technique.

PMID- 24448183
TI  - Elucidating the severity of preclinical traumatic brain injury models: a role for
      functional assessment?
AB  - BACKGROUND: Concussion remains a symptom-based diagnosis clinically, yet
      preclinical studies investigating traumatic brain injury, of which concussion is
      believed to represent a "mild" form, emphasize histological end points with
      functional assessments often minimized or ignored all together. Recently,
      clinical studies have identified the importance of cognitive and neuropsychiatric
      symptoms, in addition to somatic concerns, following concussion. How these
      findings may translate to preclinical studies is unclear at present. OBJECTIVE:
      To address the contrasting end points used clinically compared with those in
      preclinical studies and the potential role of functional assessments in a
      commonly used model of diffuse axonal injury (DAI). METHODS: Animals were
      subjected to DAI by the use of the impact-acceleration model. Functional and
      behavioral assessments were conducted during 1 week following DAI before the
      completion of the histological assessment at 1 week post-DAI. RESULTS: We show,
      despite the suggestion that this model represents concussive injury, no
      functional impairments as determined by using the common measures of motor,
      sensorimotor, cognitive, and neuropsychiatric function following injury over the
      course of 1 week. The lack of functional deficits is in sharp contrast to
      neuropathological findings indicating neural degeneration, astrocyte reactivity,
      and microglial activation. CONCLUSION: Future studies are needed to identify
      functional assessments, neurophysiologic techniques, and imaging assessments more
      apt to distinguish differences following so-called "mild" traumatic brain injury
      in preclinical models and determine whether these models are truly studying
      concussive or subconcussive injury. These studies are needed not only to
      understand the mechanism of injury and production of subsequent deficits, but
      also to rigorously evaluate potential therapeutic agents.

PMID- 24448185
TI  - Using higher isodose lines for gamma knife treatment of 1 to 3 brain metastases
      is safe and effective.
AB  - BACKGROUND: Higher isodose lines (IDLs) in Gamma Knife (GK) Perfexion treatment
      of brain metastases (BMet) could result in lower local control (LC) or higher
      radiation necrosis (RN) rates, but reduce treatment time. OBJECTIVE: To assess
      the impact of the heterogeneity index (HI) and conformality index (CFI) ion local
      failure (LF) for patients treated with GK for 1 to 3 BMet. METHODS: From an
      institutional review board-approved database, 320 patients with 496 BMet were
      identified, treated for 1 to 3 BMet from July 2007 to April 2011 on GK Perfexion.
      Cox proportional hazards regression was used to analyze significance of HI, CFI,
      IDL, dose, tumor diameter, recursive partitioning analysis class, tumor
      radioresistance, primary, smoking history, metastasis location, and whole-brain
      radiation therapy (WBRT) history with LF and RN. RESULTS: Median follow-up by
      lesion was 6.8 months (range, 0-49.6). The series median survival was 14.2
      months. Per RECIST, 9.5% of lesions failed, 33.9% were stable, 38.3% partially
      responded, 17.1% responded completely, and 1.2% could not be assessed. The 12
      month LC rate was 87.3%. On univariate analysis, a dose less than 20 Gy (hazard
      ratio [HR]: 2.940, P < .001); tumor size (HR: 1.674, P < .001); and
      cerebellum/brainstem location vs other (HR: 1.891, P = .043) were significant for
      LF. Non-small cell lung cancer (HR: 0.333, P = .0097) was associated with better
      LC. On multivariate analysis, tumor size (HR: 1.696, P < .001) and
      cerebellum/brainstem location vs other (HR: 1.959, P = .033) remained significant
      for LF. Variables not significant for LF included CI, IDL, and HI. CONCLUSION:
      Our study of patients with 1 to 3 BMet treated with GK demonstrated no difference
      in LC or RN with varying HI, indicating that physicians can treat to IDL at 70%
      or higher IDL to reduce treatment time without increased LF or RN.

PMID- 24448186
TI  - Microsurgical anatomy of the white matter tracts in hemispherotomy.
AB  - BACKGROUND: Hemispherotomy is a surgical procedure performed for refractory
      epileptic seizures due to wide hemispheric damage. OBJECTIVE: To describe the
      microanatomy of the white matter tracts transected in a hemispherotomy and the
      relationship of the surgical landmarks used during the intraventricular
      callosotomy. METHODS: The cortical and subcortical structures were examined in 32
      hemispheres. RESULTS: Incision of the temporal stem along the inferior limiting
      sulcus crosses the insulo-opercular fibers, uncinate, inferior occipitofrontal
      and middle longitudinal fasciculi, anterior commissure, and optic and auditory
      radiations. The incision along the superior limiting sulcus transects insulo
      opercular fibers and the genu and posterior limb of internal capsule. The
      incision along the anterior limiting sulcus crosses the insulo-opercular fibers,
      anterior limb of the internal capsule, anterior commissure, and the anterior
      thalamic bundle. The disconnection of the posterior part of the corpus callosum
      may be incomplete if the point at which the last cortical branch of the anterior
      cerebral artery (ACA) turns upward and disappears from the view through the
      intraventricular exposure is used as the landmark for estimating the posterior
      extent of the callosotomy. This ACA branch turns upward before reaching the
      posterior edge of the splenium in 85% of hemispheres. The falx, followed to the
      posterior edge of the splenium, is a more reliable landmark for completing the
      posterior part of an intraventricular callosotomy. CONCLUSION: The fiber tracts
      disconnected in hemispherotomy were reviewed. The falx is a more reliable guide
      than the ACA in completing the posterior part of the intraventricular
      callosotomy.

PMID- 24448187
TI  - Multidisciplinary approach for improved outcomes in secondary cranial
      reconstruction: introducing the pericranial-onlay cranioplasty technique.
AB  - BACKGROUND: Although materials for secondary cranial reconstruction have evolved
      with time, the overall approach in terms of bone flap/implant reconstruction
      after necessary delay has remained constant. OBJECTIVE: To present our cases
      series of 50 consecutive secondary cranial reconstruction patients and to
      describe a multidisciplinary cranioplasty approach developed to reduce morbidity,
      to minimize infection, and to improve aesthetic appearance. METHODS: Standard
      technique teaches us to place the bone flap and/or alloplastic implant directly
      over the dura or dural protectant after scalp flap re-elevation. However, this
      procedure is fraught with high complication rates, including infection. While
      raising the previously incised scalp flap overlying the full-thickness calvarial
      defect, the dissection is performed within the loose areolar tissue plane beneath
      the galea aponeurosis, thus leaving vascularized pericranium intact over the
      dura. RESULTS: A total of 50 consecutive patients were treated by the senior
      author encompassing 46 cranioplasties using the pericranial-onlay approach, along
      with 4 isolated temporal soft tissue reconstructions with liquid poly-methyl
      methacrylate. Of the 46 cranioplasties (> 5 cm), only 1 autologous bone flap
      developed deep infection necessitating bone flap removal (1 of 46, 2.17%; 95%
      confidence interval, 0.003-11.3). None of the alloplastic custom implants placed
      have developed any infection requiring removal. CONCLUSION: This
      multidisciplinary approach illustrated in our case series, including our
      "pericranial-onlay" technique described here for the first time, has the
      potential to improve patient outcomes, to decrease perioperative morbidity, and
      to minimize costs associated with postoperative infections after secondary
      cranial reconstruction.

PMID- 24448189
TI  - Unusual presentation of sacral fatigue fractures.

PMID- 24448188
TI  - Proton beam stereotactic radiosurgery for pediatric cerebral arteriovenous
      malformations.
AB  - BACKGROUND: For cerebral arteriovenous malformations (AVMs) determined to be high
      risk for surgery or endovascular embolization, stereotactic radiosurgery (SRS) is
      considered the mainstay of treatment. OBJECTIVE: To determine the outcomes of
      pediatric patients with AVMs treated with proton SRS. METHODS: We reviewed the
      records of 44 consecutively treated pediatric patients (younger than 18 years of
      age) who underwent proton SRS at our institution from 1998 to 2010. The median
      target volume was 4.5 +/- 5.9 mL (range, 0.3-29.0 mL) and the median maximal
      diameter was 3.6 +/- 1.5 cm (range, 1-6 cm). Radiation was administered with a
      median prescription dose of 15.50 +/- 1.87 CGE to the 90% isodose. RESULTS: At a
      median follow-up of 52 +/- 25 months, 2 patients (4.5%) had no response, 24
      patients (59.1%) had a partial response, and 18 patients (40.9%) experienced
      obliteration of their AVM. The median time to obliteration was 49 +/- 26 months,
      including 17 patients who underwent repeat proton radiosurgery. Four patients
      (9%) experienced hemorrhage after treatment at a median time of 45 +/- 15 months.
      Univariate analysis identified modified AVM scale score (P = .045), single
      fraction treatment (0.04), larger prescription dose (0.01), larger maximum dose
      (<0.001), and larger minimum dose (0.01) to be associated with AVM obliteration.
      CONCLUSION: High-risk AVMs can be safely treated with proton radiosurgery in the
      pediatric population. Because protons deposit energy more selectively than
      photons, there is the potential benefit of protons to lower the probability of
      damage to healthy tissue in the developing brain.

PMID- 24448190
TI  - Cauda equina syndrome secondary to bilateral sacral Tarlov cysts.

PMID- 24448191
TI  - Extended costotransversectomy to achieve circumferential fusion for pathologies
      causing thoracic instability.
AB  - BACKGROUND CONTEXT: Conventional circumferential stabilization for pathologies
      causing instability of the thoracic spine requires a two or even a three-staged
      procedure. The authors present their tertiary care center experience of single
      staged procedure to establish a circumferential fusion through an extended
      costotransversectomy approach. OBJECTIVE: To demonstrate neural canal
      decompression, removal of the pathology, achieve circumferential fusion, and
      correcting the deformity through a single procedure. STUDY DESIGN: Prospective
      and observational. PATIENT SAMPLE: Forty-six patients with pan thoracic column
      instability due to various pathologies. OUTCOME MEASURES: Neurologic condition
      was evaluated using American Spinal Injury Association and Eastern Cooperative
      Oncology Group grading systems. Outcome was evaluated with regard to the
      decompression of neural canal, correction of deformity, and neurologic
      improvement. All patients were evaluated for neural canal compromise and degree
      of kyphosis preoperatively, early, and late postoperatively. METHODS: All
      patients had severe spinal canal compromise (mean, 59%+/-9%) and loss of
      vertebral body height (mean, 55%+/-10%). A single-stage circumferential fusion
      was performed (four-level pedicle screw fixation along with a ventral cage
      fixation after a vertebrectomy or corpectomy) through an extended
      costotransversectomy approach. RESULTS: The pathologies included trauma (21),
      tuberculosis (18), hemangioma (2), aneurysmal bone cyst (1), recurrent
      hemangioendothelioma (1), solitary metastasis (1) and plasmacytoma (1), and
      neurofibromatosis (1). Thirty-five of 46 patients (76%) demonstrated improvement
      in the performance status. The major complications included pneumonitis (3),
      pneumothorax (3) and neurologic deterioration (3; improved in two), deep venous
      thrombosis (2), and recurrent hemoptysis (1). No implant failures were noted on
      last radiology follow-up. There were two mortalities; one because of myocardial
      infarction and another because of respiratory complications. CONCLUSIONS: The
      following study demonstrated that extended costotrasversectomy approach is a good
      option for achieving single-staged circumferential fusion for correcting unstable
      thoracic spine due to both traumatic and nontraumatic pathologies.

PMID- 24448192
TI  - Reconstruction with expandable cages after single- and multilevel corpectomies
      for spinal metastases: a prospective case series of 60 patients.
AB  - BACKGROUND CONTEXT: Expandable cages are widely used to reconstruct the spine
      after the removal of vertebral metastases. Long-term results, however, are
      lacking, and there is little information on reconstruction after multilevel
      corpectomies. PURPOSE: To determine long-term outcome for reconstruction of the
      spine with expandable cages after single and multilevel corpectomies for spinal
      metastases. STUDY DESIGN: A prospective cohort study of 60 consecutive patients
      with spinal metastases treated with expandable cages. METHODS: All patients were
      prospectively followed with regular clinical and radiographic evaluation. Outcome
      measures were the Frankel score, patients' self-reported recovery, radiological
      alignment of the spine, and neurologic plus biomechanical complications. RESULTS:
      Sixty patients were treated with expandable cages in our hospital in a 5-year
      period with a maximum follow-up of 6 years. Single-level reconstruction was
      performed in 48 cases, 2-level in 8, and 3-level in 4. Postoperatively, the
      Frankel score had improved significantly (p=.03), the segment height had
      increased (p=.02), and, in severe cases of kyphosis (>20 degrees ), the regional
      angulation had been corrected compared with preoperatively (p<.001). Complication
      rate, however, was high (36.7%), in particular after multilevel reconstruction,
      in which three cases had to be reoperated years after the initial surgery;
      reasons for this were hardware failure, progressive kyphosis, and bronchial
      perforation. Good recovery was reported in 70% of all patients. CONCLUSIONS:
      Expandable cages can be used successfully in reconstruction of the spine after
      single and multilevel corpectomies for spinal metastases. However, long-term
      complication rate is high. Promotion of bony fusion, prevention of soft-tissue
      damage, adequate posterior stabilization, and careful patient selection may
      reduce these complications.

PMID- 24448193
TI  - Radiographic fusion rate after implantation of facet bone dowels.
AB  - BACKGROUND CONTEXT: Achieving a posterolateral fusion in conjunction with
      performing decompressive laminectomies can prevent recurrence of stenosis or
      worsening of spondylolisthesis. Facet bone dowels have been introduced and
      marketed as a less invasive alternative to pedicle screws. Surgeons have been
      placing them during lumbar laminectomy surgery and coding for intervertebral
      biomechanical device and posterolateral fusion. These bone dowels have also been
      placed percutaneously in outpatient surgery centers and pain clinics for facet
      mediated back pain. PURPOSE: To describe fusion outcomes in patients who
      underwent facet bone dowel placement. STUDY DESIGN/SETTING: Retrospective
      analysis of a single center's experience. PATIENT SAMPLE: Ninety-six patients
      comprise the entire cohort of patients who underwent facet bone dowel
      implantation at our institution with adequate postoperative imaging to determine
      fusion status. OUTCOME MEASURES: Fusion rates as determined on postoperative
      computed tomography (CT) scans and dynamic lumbar X-rays if CT is not available.
      METHODS: Threaded facet bone dowels in this study were placed according to the
      manufacturer's recommended methods. The bone dowels were placed after open
      exploration of the facet complex or percutaneously through a tubular retractor on
      the contralateral side from a microdiscectomy or synovial cyst resection. The
      most recent available postoperative imaging was reviewed to determine fusion
      status. RESULTS: Of 96 patients in our series, 6 (6.3%) had a fusion seen on CT
      and 4 did not exhibit any movement on dynamic lumbar X-rays for a total fusion
      rate of 10.4% (10/96). Eighty-six (89.6%) patients were shown on imaging to not
      have a solid fusion either by visualizing a patent facet joint on CT or
      measurable movement between the flexion and the extension lumbar X-rays.
      CONCLUSIONS: This article is mainly intended to question whether the implantation
      of facet bone dowels can produce a solid fusion radiographically. In our
      experience, the placement of facet bone dowels does not equal the time, skill, or
      attention to detail that is necessary for a posterolateral lumbar arthrodesis,
      and our follow-up radiographic studies clearly demonstrate an inadequate fusion
      rate.

PMID- 24448194
TI  - Age-related changes in serological susceptibility patterns to measles: results
      from a seroepidemiological study in Dongguan, China.
AB  - The present study was performed to determine the seroprevalence of IgG measles
      antibodies in Dongguan residents (irrespective of vaccination status), to analyze
      the changes in age-related serological susceptibility patterns. A total of 1960
      residents aged 0-60 years and 315 mother-infant pairs were studied. Serum IgG
      antibodies against measles virus were measured by ELISA. The overall
      seroprevalence was 93.4% in the general population in Dongguan, China. In
      subgroups aged 1-29 years who were likely vaccinated, there was a declining trend
      of seropositivity with age from 98.6% at 1-4 years to 85.7% at 20-29 years
      (P<0.0001). Seroprevalence were near or>95% in the older population (30-39 years
      and >= 40 years) who had not been immunized against measles. Age and sex were
      independent factors associated with seropositivity. Seroprevalence in pregnant
      women and their newborns was 87.0% and 84.1%, respectively. Our results suggest
      that the waning vaccine-induced immunity may be the main cause of increased
      serological susceptibility in young adults and young infants. An additional
      vaccination strategy that targets young adults is important for elimination of
      measles.

PMID- 24448195
TI  - Novel Ex Vivo Culture Method for the Study of Dupuytren's Disease: Effects of
      TGFbeta Type 1 Receptor Modulation by Antisense Oligonucleotides.
AB  - Dupuytren's disease (DD) is a benign fibroproliferative disease of the hand. It
      is characterized by the excessive production of extracellular matrix (ECM)
      proteins, which form a strong fibrous tissue between the handpalm and fingers,
      permanently disrupting the fine movement ability. The major contractile element
      in DD is the myofibroblast (MFB). This cell has both fibroblast and smooth muscle
      cell-type characteristics and causes pathological collagen deposition. MFBs
      generate contractile forces that are transmitted to the surrounding collagen
      matrix. MUajor profibrotic factors are members of the transforming growth factor
      beta (TGFbeta) pathway which directly regulate the expression levels of several
      fibrous proteins such as collagen type 1, type 3, and alpha-smooth muscle actin.
      Molecular modulation of this signaling pathway could serve as a therapeutic
      approach. We, therefore, have developed an ex vivo "clinical trial" system to
      study the properties of intact, patient-derived resection specimens. In these
      culture conditions, Dupuytren's tissue retains its three-dimensional (3D)
      structure and viability. As a novel antifibrotic therapeutic approach, we
      targeted TGFbeta type 1 receptor (also termed activin receptor-like kinase 5)
      expression in cultured Dupuytren's specimens by antisense oligonucleotide
      mediated exon skipping. Antisense oligonucleotides targeting activin receptor
      like kinase 5 showed specific reduction of ECM and potential for clinical
      application.Molecular Therapy-Nucleic Acids (2014) 3, e142;
      doi:10.1038/mtna.2013.69; published online 21 January 2014. 

PMID- 24448196
TI  - The association of red cell distribution width at hospital discharge and out-of
      hospital mortality following critical illness*.
AB  - OBJECTIVES: Red cell distribution width is associated with mortality and
      bloodstream infection risk in the critically ill. In hospitalized patients with
      critical illness, it is not known if red cell distribution width can predict
      subsequent risk of all-cause mortality following hospital discharge. We
      hypothesized that an increase in red cell distribution width at hospital
      discharge in patients who survived to discharge following critical care would be
      associated with increased postdischarge mortality. DESIGN: Two-center
      observational cohort study SETTING: : All medical and surgical ICUs at the
      Brigham and Women's Hospital and Massachusetts General Hospital. PATIENTS: We
      studied 43,212 patients, who were 18 years old or older and received critical
      care between 1997 and 2007 and survived hospitalization. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The exposure of interest was red cell distribution
      width within 24 hours of hospital discharge and categorized a priori in quintiles
      as less than or equal to 13.3%, 13.3-14.0%, 14.0-14.7%, 14.7-15.8%, and more than
      15.8%. The primary outcome was all-cause mortality in the 30 days following
      hospital discharge. Secondary outcomes included 90-day and 365-day mortality
      following hospital discharge. Mortality was determined using the U.S. Social
      Security Administration Death Master File, and 365-day follow-up was present in
      all cohort patients. Adjusted odds ratios were estimated by multivariable
      logistic regression models with inclusion of covariate terms thought to plausibly
      interact with both red cell distribution width and mortality. Adjustment included
      age, race, gender, Deyo-Charlson Index, patient type (medical vs surgical),
      sepsis, and number of organs with acute failure. In patients who received
      critical care and survived hospitalization, the discharge red cell distribution
      width was a robust predictor of all-cause mortality and remained so following
      multivariable adjustment. Patients with a discharge red cell distribution width
      of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality
      in the 30 days following hospital discharge of 2.86 (95% CI, 2.25-3.62), 4.57
      (95% CI, 3.66-5.72), and 8.80 (95% CI, 7.15-10.83), respectively, all relative to
      patients with a discharge red cell distribution width less than or equal to
      13.3%. Following multivariable adjustment, patients with a discharge red cell
      distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds
      ratio for mortality in the 30 days following hospital discharge of 1.63 (95% CI,
      1.27-2.07), 2.36 (95% CI, 1.87-2.97), and 4.18 (95% CI, 3.36-5.20), respectively,
      all relative to patients with a discharge red cell distribution width less than
      or equal to 13.3%. Similar significant robust associations post multivariable
      adjustments are seen with death by days 90 and 365 postdischarge. Estimating the
      receiver-operating characteristic area under the curve shows that discharge red
      cell distribution width has moderate discriminative power for mortality 30 days
      following hospital discharge (area under the curve = 0.70; SE 0.006; 95% CI, 0.69
      0.71; p < 0.0001). CONCLUSION: In patients treated with critical care who survive
      hospitalization, an elevated red cell distribution width at the time of discharge
      is a robust predictor of subsequent all-cause patient mortality. Increased
      discharge red cell distribution width likely reflects the presence of
      proinflammatory state, oxidative stress, arterial underfilling, or a combination,
      thereof which may explain the observed impact on patient survival following
      discharge. Elevated red cell distribution width at hospital discharge may
      identify ICU survivors who are at risk for adverse outcomes following hospital
      discharge.

PMID- 24448197
TI  - Early inflammation mainly affects normally and poorly aerated lung in
      experimental ventilator-induced lung injury*.
AB  - OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury
      is an intense inflammatory response mediated by neutrophils. PET with
      [(18)F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which,
      during lung inflammatory processes, mainly reflects neutrophil activity, allowing
      the study of regional lung inflammation in vivo. The aim of this study was to
      assess the location and magnitude of lung inflammation using PET imaging of
      [(18)F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute
      respiratory distress syndrome. DESIGN: Prospective laboratory investigation.
      SETTING: A university animal research laboratory. SUBJECTS: Seven piglets
      submitted to experimental ventilator-induced lung injury and five healthy
      controls. INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes
      of injurious mechanical ventilation using low positive end-expiratory pressure
      and high inspiratory pressures. All animals were subsequently studied with
      dynamic PET imaging of [(18)F]fluoro-2-deoxy-D-glucose. CT scans were acquired at
      end expiration and end inspiration. MEASUREMENTS AND MAIN RESULTS: [(18)F]fluoro
      2-deoxy-D-glucose uptake rate was computed for the whole lung, four
      isogravitational regions, and regions grouping voxels with similar density.
      Global and intermediate gravitational zones [(18)F]fluoro-2-deoxy-D-glucose
      uptakes were higher in ventilator-induced lung injury piglets compared with
      controls animals. Uptake of normally and poorly aerated regions was also higher
      in ventilator-induced lung injury piglets compared with control piglets, whereas
      regions suffering tidal recruitment or tidal hyperinflation had [(18)F]fluoro-2
      deoxy-D-glucose uptakes similar to controls. CONCLUSIONS: The present findings
      suggest that normally and poorly aerated regions--corresponding to intermediate
      gravitational zones--are the primary targets of the inflammatory process
      accompanying early experimental ventilator-induced lung injury. This may be
      attributed to the small volume of the aerated lung, which receives most of
      ventilation.

PMID- 24448198
TI  - C4d deposits on the surface of RBCs in trauma patients and interferes with their
      function.
AB  - OBJECTIVE: Complement system is activated in patients with trauma. Although
      complement activation is presumed to contribute to organ damage and
      constitutional symptoms, little is known about the involved mechanisms. Because
      complement components may deposit on RBCs, we asked whether complement deposits
      on the surface of RBC in trauma and whether such deposition alters RBC function.
      DESIGN: A prospective experimental study. SETTING: Research laboratory. SUBJECTS:
      Blood samples collected from 42 trauma patients and 21 healthy donors.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: RBC and sera were collected
      from trauma patients and control donors. RBCs from trauma patients (n = 40) were
      found to display significantly higher amounts of C4d on their surface by flow
      cytometry compared with RBCs from control (n = 17) (p < 0.01). Increased amounts
      of iC3b were found in trauma sera (n = 27) (vs 12 controls, p < 0.01) by enzyme
      linked immunosorbent assay. Incubation of RBC from universal donors (type O, Rh
      negative) with trauma sera (n = 10) promoted C4d deposition on their surface (vs
      six controls, p< 0.05). Complement-decorated RBC (n = 6) displayed limited their
      deformability (vs six controls, p < 0.05) in two-dimensional microchannel arrays.
      Incubation of RBC with trauma sera (n = 10) promoted the phosphorylation of band
      3, a cytoskeletal protein important for the function of the RBC membrane (vs
      eight controls, p < 0.05), and also accelerated calcium influx (n = 9) and
      enhanced nitric oxide production (n = 12) (vs four and eight controls
      respectively, p < 0.05) in flow cytometry. CONCLUSIONS: Our study found the
      presence of extensive complement activation in trauma patients and presents new
      evidence in support of the hypothesis that complement activation products deposit
      on the surface of RBC. Such deposition could limit RBC deformability and promote
      the production of nitric oxide. Our findings suggest that RBC in trauma patients
      malfunctions, which may explain organ damage and constitutional symptoms that is
      not accounted for otherwise by previously known pathophysiologic mechanisms.

PMID- 24448199
TI  - Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down
      regulation of cardiac fibroblasts-derived fibroblast growth factor-2.
AB  - OBJECTIVE: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play
      a protective role in cardiac hypertrophy, but the mechanism is not fully
      understood. We tested the hypothesis that deletion of soluble epoxide hydrolase
      attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived
      fibroblast growth factor-2. DESIGN: Prospective, controlled, and randomized
      animal study. SETTING: University laboratory. SUBJECTS: Male wild-type C57BL/6
      mice and Ephx2 (-/-) mice. INTERVENTIONS: Male wild-type or Ephx2 (-/-) mice were
      subjected to transverse aorta constriction surgery. MEASUREMENTS AND MAIN
      RESULTS: Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not
      develop significant cardiac hypertrophy as that of wild-type mice, indicated by
      no changes in the ratio of heart weight/body weight and ventricular wall
      thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2
      increased in wild-type-transverse aorta constriction group but this did not
      change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of
      fibroblast growth factor-2 did not change in both groups. In vitro, cardiac
      fibroblasts were stimulated by angiotensin II to analyze the expression of
      fibroblast growth factor-2. The effect of increased fibroblast growth factor-2
      from cardiac fibroblasts induced by angiotensin II was attenuated by soluble
      epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in
      fibroblast growth factor-2 expression regulated by angiotensin II, and soluble
      epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT
      to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide
      hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by
      exogenous fibroblast growth factor-2. CONCLUSIONS: Our present data demonstrated
      that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only
      directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression
      of fibroblast growth factor-2.

PMID- 24448200
TI  - Authors' reply to Matthys.

PMID- 24448201
TI  - Diameter control of single-walled carbon nanotube forests from 1.3-3.0 nm by arc
      plasma deposition.
AB  - We present a method to both precisely and continuously control the average
      diameter of single-walled carbon nanotubes in a forest ranging from 1.3 to 3.0 nm
      with ~1 A resolution. The diameter control of the forest was achieved through
      tuning of the catalyst state (size, density, and composition) using arc plasma
      deposition of nanoparticles. This 1.7 nm control range and 1 A precision exceed
      the highest reports to date.

PMID- 24448202
TI  - Hybrid phage displaying SLAQVKYTSASSI induces protection against Candida albicans
      challenge in BALB/c mice.
AB  - The polymorphic fungus Candida albicans (C. albicans) can live as an aggressive
      pathogen and cause many diseases in hosts, for which no effective vaccine exists.
      The secreted aspartyl proteinase 2 (Sap2) plays a protective role in systemically
      infected BALB/c mice. Protective cellular immune responses can be preferentially
      induced when antigens are displayed on small particles. Therefore, the emphasis
      is placed on developing new phage vaccine to inhibit C. albicans infection. In
      this study, the ability of the hybrid phage displaying the epitope SLAQVKYTSASSI
      and recombinant protein of Sap2 (rSap2) for inducing immune protective responses
      against C. albicans infection was evaluated by lymphoproliferative assay, to
      gather cytokine and antibody measurements in BALB/c mice. Our results showed
      that, strong cellular and humoral immune responses were induced in a mouse model
      immunized with hybrid phage or rSap2. Furthermore, the protection against lethal
      challenge with C. albicans was observed in mice vaccinated hybrid phage without
      adjuvant. These findings demonstrate that the hybrid phage displaying the epitope
      SLAQVKYTSASSI might be a potential vaccine against C. albicans infections. 

PMID- 24448203
TI  - Clear microstructure-performance relationships in Mn-containing perovskite and
      hexaaluminate compounds prepared by activated reactive synthesis.
AB  - Microstructural properties of mixed oxides play essential roles in their oxygen
      mobility and consequently in their catalytic performances. Two families of mixed
      oxides (perovskite and hexaaluminate) with different microstructural features,
      such as crystal size and specific surface area, were prepared using the activated
      reactive synthesis (ARS) method. It was shown that ARS is a flexible route to
      synthesize both mixed oxides with nano-scale crystal size and high specific
      surface area. Redox properties and oxygen mobility were found to be strongly
      affected by the material microstructure. Catalytic activities of hexaaluminate
      and perovskite materials for methane oxidation were discussed in the light of
      structural, redox and oxygen mobility properties. 

PMID- 24448205
TI  - Investigation of a dichlorodioxomolybdenum(VI)-pyrazolylpyridine complex and a
      hybrid derivative as catalysts in olefin epoxidation.
AB  - Treatment of the solvent adduct [MoO(2)Cl(2)(THF)(2)] with the ligand 2-(1-pentyl
      3-pyrazolyl)pyridine (1, abbreviated as pent-pp) gave the dioxomolybdenum(VI)
      complex [MoO(2)Cl(2)(pent-pp)] (2), which was characterised by elemental
      analysis, (1)H NMR, FT-IR spectroscopy and single crystal X-ray diffraction
      (XRD). Reaction of 2 with water in a Teflon-lined stainless steel autoclave at
      100  degrees C led to the isolation of a molybdenum oxide/pyrazolylpyridine
      hybrid material with the composition [Mo(2)O(6)(pent-pp)] (3), which was
      characterised by variable temperature powder XRD, scanning electron microscopy,
      thermogravimetric analysis, FT-IR and (13)C{(1)H} CP MAS NMR spectroscopies.
      Compounds 2 and 3 display high activity and selectivity when used as
      (pre)catalysts for the epoxidation of cis-cyclooctene at 55  degrees C with tert
      butylhydroperoxide as an oxidant. Further catalytic experiments with 3 as a
      (pre)catalyst were performed using the bio-derived olefins DL-limonene (Lim) and
      methyl oleate (Ole). The reaction of Lim gave mainly 1,2-epoxy-p-menth-8-ene and
      1,2;8,9-diepoxy-p-menthane in a combined yield of 93% at 97% conversion (6 h),
      while the reaction of Ole led to 9,10-epoxystearate as the main product in 78%
      yield at 82% conversion (6 h). The catalytic reactions are homogeneous in nature.
      Starting with material 3, the oxodiperoxo complex [MoO(O(2))(2)(pent-pp)] (4) was
      isolated from solution after a catalytic run, suggesting that it is formed from 3
      and plays a catalytic role.

PMID- 24448204
TI  - Using semantic predications to uncover drug-drug interactions in clinical data.
AB  - In this study we report on potential drug-drug interactions between drugs
      occurring in patient clinical data. Results are based on relationships in
      SemMedDB, a database of structured knowledge extracted from all MEDLINE citations
      (titles and abstracts) using SemRep. The core of our methodology is to construct
      two potential drug-drug interaction schemas, based on relationships extracted
      from SemMedDB. In the first schema, Drug1 and Drug2 interact through Drug1's
      effect on some gene, which in turn affects Drug2. In the second, Drug1 affects
      Gene1, while Drug2 affects Gene2. Gene1 and Gene2, together, then have an effect
      on some biological function. After checking each drug pair from the medication
      lists of each of 22 patients, we found 19 known and 62 unknown drug-drug
      interactions using both schemas. For example, our results suggest that the
      interaction of Lisinopril, an ACE inhibitor commonly prescribed for hypertension,
      and the antidepressant sertraline can potentially increase the likelihood and
      possibly the severity of psoriasis. We also assessed the relationships extracted
      by SemRep from a linguistic perspective and found that the precision of SemRep
      was 0.58 for 300 randomly selected sentences from MEDLINE. Our study demonstrates
      that the use of structured knowledge in the form of relationships from the
      biomedical literature can support the discovery of potential drug-drug
      interactions occurring in patient clinical data. Moreover, SemMedDB provides a
      good knowledge resource for expanding the range of drugs, genes, and biological
      functions considered as elements in various drug-drug interaction pathways. 

PMID- 24448206
TI  - Microscale thermophoresis provides insights into mechanism and thermodynamics of
      ribozyme catalysis.
AB  - The analysis of binding interactions between small molecules and biopolymers is
      important for understanding biological processes. While fluorescence correlation
      spectroscopy (FCS) requires fluorescence labeling on the small molecule, which
      often interferes with binding, in microscale thermophoresis (MST) the label can
      be placed on the biopolymer. Ribozymes have not been analyzed by MST so far. The
      Diels-Alderase ribozyme (DAse) is a true catalyst, facilitating the Diels-Alder
      reaction between two free small substrates, anthracene dienes, and maleimide
      dienophiles. Despite high efforts, the determination of the dissociation constant
      (KD) of maleimide dienophiles to the DAse by FCS has been unsuccessful. Here, we
      determined the binding interactions of the DAse to its substrates and the Diels
      Alder product using MST. The results supported a positive cooperativity for
      substrate binding to the DAse. By varying the temperature, we furthermore studied
      the thermodynamics of dienophile dissociation. The entropic contribution was
      found to be the energetic driving force for the binding of the dienophile to the
      DAse. 

PMID- 24448207
TI  - [Ag(70)(PW(9)O(34))(2)((t)BuC[triple bond, length as m
      dash]C)(44)(H(2)O)(2)](8+): ionothermal synthesis of a silver cluster
      encapsulating lacunary polyoxometalate ions.
AB  - A silver alkynyl cluster containing a Ag70 shell and two lacunary [PW9O34](9-)
      templating ions was synthesized by an ionothermal approach. Fast core-shell
      electronic communication between silver(i) centers and polyoxometalates was
      verified via cyclic voltammetry studies in [BMIm]BF4. 

PMID- 24448208
TI  - A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for
      nephrotoxicity and renal carcinogenicity.
AB  - Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear
      factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the
      cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of
      oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II
      metabolism inducibility. The effects combined would render the cell and tissue
      more vulnerable to oxidative stress. Indeed, Nrf2 knock out animals exhibit
      increased susceptibility to various types of chemical-induced injury. Several
      studies have shown that OTA exposure can inhibit Nrf2 responses. Such an action
      would initially lead to increased susceptibility to both physiological and
      chemical-induced cell stress. However, chronic exposure to OTA may also act as a
      selective pressure for somatic mutations in Nrf2 or its inhibitor Keap-1, leading
      to constitutive Nrf2 activation. Nrf2 overexpression confers a survival advantage
      and is often associated with cancer cell survival. Here we review the evidence
      for OTA's role as an Nrf2 inhibitor and discuss the implications of this
      mechanism in nephrotoxicity and carcinogenicity. 

PMID- 24448209
TI  - The genome-wide landscape of DNA methylation and hydroxymethylation in response
      to sleep deprivation impacts on synaptic plasticity genes.
AB  - Sleep is critical for normal brain function and mental health. However, the
      molecular mechanisms mediating the impact of sleep loss on both cognition and the
      sleep electroencephalogram remain mostly unknown. Acute sleep loss impacts brain
      gene expression broadly. These data contributed to current hypotheses regarding
      the role for sleep in metabolism, synaptic plasticity and neuroprotection. These
      changes in gene expression likely underlie increased sleep intensity following
      sleep deprivation (SD). Here we tested the hypothesis that epigenetic mechanisms
      coordinate the gene expression response driven by SD. We found that SD altered
      the cortical genome-wide distribution of two major epigenetic marks: DNA
      methylation and hydroxymethylation. DNA methylation differences were enriched in
      gene pathways involved in neuritogenesis and synaptic plasticity, whereas large
      changes (>4000 sites) in hydroxymethylation where observed in genes linked to
      cytoskeleton, signaling and neurotransmission, which closely matches SD-dependent
      changes in the transcriptome. Moreover, this epigenetic remodeling applied to
      elements previously linked to sleep need (for example, Arc and Egr1) and synaptic
      partners of Neuroligin-1 (Nlgn1; for example, Dlg4, Nrxn1 and Nlgn3), which we
      recently identified as a regulator of sleep intensity following SD. We show here
      that Nlgn1 mutant mice display an enhanced slow-wave slope during non-rapid eye
      movement sleep following SD but this mutation does not affect SD-dependent
      changes in gene expression, suggesting that the Nlgn pathway acts downstream to
      mechanisms triggering gene expression changes in SD. These data reveal that acute
      SD reprograms the epigenetic landscape, providing a unique molecular route by
      which sleep can impact brain function and health. 

PMID- 24448210
TI  - Novel implications of Lingo-1 and its signaling partners in schizophrenia.
AB  - Myelination and neurite outgrowth both occur during brain development, and their
      disturbance has been previously been implicated in the pathophysiology of
      schizophrenia. Leucine-rich repeat and immunoglobulin domain-containing protein
      (Lingo-1) is a potent negative regulator of axonal myelination and neurite
      extension. As co-factors of Lingo-1 signaling (Nogo receptor (NgR), With No
      Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1)) have been implicated
      in the genetics of schizophrenia, we explored for the first time the role of
      Lingo-1 signaling pathways in this disorder. Lingo-1 protein, together with its
      co-receptor and co-factor proteins NgR, tumor necrosis factor (TNF) receptor
      orphan Y (TROY), p75, WNK1 and Myt1, have never been explored in the pathogenesis
      of schizophrenia. We examined protein levels of Lingo-1, NgR, TROY, p75, WNK1,
      Myt1 and myelin basic protein (MBP) (as a marker of myelination) within the post
      mortem dorsolateral prefrontal cortex (DLPFC) (37 schizophrenia patients versus
      37 matched controls) and hippocampus (Cornu Ammonis, CA1 and CA3) (20
      schizophrenia patients versus 20 matched controls from the same cohort). Both of
      these brain regions are highly disrupted in the schizophrenia pathophysiology.
      There were significant increases in Lingo-1 (P<0.001) and Myt1 (P=0.023) and a
      reduction in NgR (P<0.001) in the DLPFC in schizophrenia subjects compared with
      controls. There were also increases in both TROY (P=0.001) and WNK1 (P=0.011) in
      the CA1 of schizophrenia subjects and, in contrast to the DLPFC, there was an
      increase in NgR (P=0.006) in the CA3 of schizophrenia subjects compared with
      controls. No significant difference was reported for MBP levels (P>0.05) between
      the schizophrenia and control groups in the three tested regions. This is the
      first time that a study has shown altered Lingo-1 signaling in the schizophrenia
      brain. Our novel findings may present a direct application for the use of a Lingo
      1 antagonist to complement current and future schizophrenia therapies. 

PMID- 24448211
TI  - Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an
      enrichment of 5-hmC in autism spectrum disorder (ASD) cerebellum.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by
      symptoms related to altered social interactions/communication and restricted and
      repetitive behaviors. In addition to genetic risk, epigenetic mechanisms (which
      include DNA methylation/demethylation) are thought to be important in the
      etiopathogenesis of ASD. We studied epigenetic mechanisms underlying the
      transcriptional regulation of candidate genes in cerebella of ASD patients,
      including the binding of MeCP2 (methyl CpG binding protein-2) to the glutamic
      acid decarboxylase 67 (GAD1), glutamic acid decarboxylase 65 (GAD2), and Reelin
      (RELN) promoters and gene bodies. Moreover, we performed methyl DNA
      immunoprecipitation (MeDIP) and hydroxymethyl DNA immunoprecipitation (hMeDIP) to
      measure total 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the
      same regions of these genes. The enrichment of 5-hmC and decrease in 5-mC at the
      GAD1 or RELN promoters detected by 5-hmC and 5-mC antibodies was confirmed by Tet
      assisted bisulfite (TAB) pyrosequencing. The results showed a marked and
      significant increase in MeCP2 binding to the promoter regions of GAD1 and RELN,
      but not to the corresponding gene body regions in cerebellar cortex of ASD
      patients. Moreover, we detected a significant increase in TET1 expression and an
      enrichment in the level of 5-hmC, but not 5-mC, at the promoters of GAD1 and RELN
      in ASD when compared with CON. Moreover, there was increased TET1 binding to
      these promoter regions. These data are consistent with the hypothesis that an
      increase of 5-hmC (relative to 5-mC) at specific gene domains enhances the
      binding of MeCP2 to 5-hmC and reduces expression of the corresponding target
      genes in ASD cerebella. 

PMID- 24448214
TI  - Prospects for the use of plant cell cultures in food biotechnology.
AB  - Plant cell cultures can offer continuous production systems for high-value food
      and health ingredients, independent of geographical or environmental variations
      and constraints. Yet despite many improvements in culture technologies, cell line
      selection, and bioreactor design, there are few commercial successes. This is
      principally due to the culture yield and market price of food products not being
      sufficient to cover the plant cell culture production costs. A better
      understanding of the underpinning biological mechanisms that control the target
      metabolite biosynthetic pathways may allow the metabolic engineering of cell
      lines to provide for economically competitive product yields. However,
      uncertainty around the regulatory and public acceptance of products derived from
      engineered cell cultures presents a barrier to the uptake of the technology by
      food product companies. 

PMID- 24448213
TI  - Regulation of Dscam exon 17 alternative splicing by steric hindrance in
      combination with RNA secondary structures.
AB  - The gene Down syndrome cell adhesion molecule (Dscam) potentially encodes 38 016
      distinct isoforms in Drosophila melanogaster via mutually exclusive splicing.
      Here we reveal a combinatorial mechanism of regulation of Dscam exon 17 mutually
      exclusive splicing through steric hindrance in combination with RNA secondary
      structure. This mutually exclusive behavior is enforced by steric hindrance, due
      to the close proximity of the exon 17.2 branch point to exon 17.1 in Diptera, and
      the interval size constraint in non-Dipteran species. Moreover, intron-exon RNA
      structures are evolutionarily conserved in 36 non-Drosophila species of six
      distantly related orders (Diptera, Lepidoptera, Coleoptera, Hymenoptera,
      Hemiptera, and Phthiraptera), which regulates the selection of exon 17 variants
      via masking the splice site. By contrast, a previously uncharacterized RNA
      structure specifically activated exon 17.1 by bringing splice sites closer
      together in Drosophila, while the other moderately suppressed exon 17.1 selection
      by hindering the accessibility of polypyrimidine sequences. Taken together, these
      data suggest a phylogeny of increased complexity in regulating alternative
      splicing of Dscam exon 17 spanning more than 300 million years of insect
      evolution. These results also provide models of the regulation of alternative
      splicing through steric hindrance in combination with dynamic structural codes. 

PMID- 24448215
TI  - An audit of half-count myocardial perfusion imaging using resolution recovery
      software.
AB  - INTRODUCTION: The Nuclear Medicine Software Quality Group of the Institute of
      Physics and Engineering in Medicine has conducted a multicentre, multivendor
      audit to evaluate the use of resolution recovery software from several
      manufacturers when applied to myocardial perfusion data with half the normal
      counts acquired under a variety of clinical protocols in a range of departments.
      The objective was to determine whether centres could obtain clinical results with
      half-count data processed with resolution recovery software that were equivalent
      to those obtained using their normal protocols. MATERIALS AND METHODS: Sixteen
      centres selected 50 routine myocardial perfusion studies each, from which the
      Nuclear Medicine Software Quality Group generated simulated half-count studies
      using Poisson resampling. These half-count studies were reconstructed using
      resolution recovery and the clinical reports compared with the original reports
      from the full-count data. A total of 769 patient studies were processed and
      compared. RESULTS: Eight centres found only a small number of clinically relevant
      discrepancies between the two reports, whereas eight had an unacceptably high
      number of discrepancies. There were no significant differences in acquisition
      parameters between the two groups, although centres finding a high number of
      discrepancies were more likely to perform both rest and stress scans on normal
      studies. CONCLUSION: Half of the participating centres could potentially make use
      of resolution recovery to reduce the administered activity for myocardial
      perfusion scans without changing their routine acquisition protocols. The other
      half could consider adjusting the reconstruction parameters used with their
      resolution recovery software if they wish to use reduced activity successfully.

PMID- 24448216
TI  - Gold(III) assisted C-H activation of 1,4,7-trithiacyclononane: synthesis and
      spontaneous resolution of a bicyclic chiral sulfonium salt.
AB  - Reaction of [9]aneS3 (1,4,7-trithiacyclononane) with KAuCl4 in nitromethane
      yields the complex [Au([9]aneS3)Cl2][AuCl4]. Heating of this salt yields the
      bicyclic sulfonium [9]aneS3(+) (4,7-dithia-1-thioniabicyclo[4,3,0]nonane) as a
      racemic [AuCl4](-) salt. Further reaction produces [[9]aneS3(+)][AuCl2], which
      undergoes spontaneous resolution upon crystallization. Each enantiomer of
      [[9]aneS3(+)][AuCl2] was crystallographically characterized as well as the
      racemic [AuCl4](-) salt. 

PMID- 24448212
TI  - Glia and immune cell signaling in bipolar disorder: insights from
      neuropharmacology and molecular imaging to clinical application.
AB  - Bipolar disorder (BD) is a debilitating mental illness characterized by severe
      fluctuations in mood, sleep, energy and executive functioning. Pharmacological
      studies of selective serotonin reuptake inhibitors and the monoamine system have
      helped us to clinically understand bipolar depression. Mood stabilizers such as
      lithium and valproic acid, the first-line treatments for bipolar mania and
      depression, inhibit glycogen synthase kinase-3 beta (GSK-3beta) and regulate the
      Wnt pathway. Recent investigations suggest that microglia, the resident immune
      cells of the brain, provide a physiological link between the serotonin system and
      the GSK-3beta/Wnt pathway through neuroinflammation. We review the
      pharmacological, translational and brain imaging studies that support a role for
      microglia in regulating neurotransmitter synthesis and immune cell activation.
      These investigations provide a model for microglia involvement in the
      pathophysiology and phenotype of BD that may translate into improved therapies. 

PMID- 24448218
TI  - The alternation effect in ionic liquid homologous series.
AB  - A recent report on a density odd-even alternation effect in a homologous series
      of ionic liquids (alkyltrioctylphosphonium chlorides, with the linear alkyl group
      ranging from ethyl to decyl) led to the detection of a similar trend in another
      ionic liquid family based on a different cation (1-alkyl-3-methylimidazolium). Ab
      initio calculations and Molecular Dynamics simulations of the corresponding ions
      confirmed that the charge distribution along the alkyl side chains and the
      conformations adopted by them are not the direct cause of the odd-even effect.
      The simulations also showed that all cation side chains tend to adopt transoid
      conformations that pack head-to-head in the liquid phase. Such types of
      conformations/packing lead to odd-even alternation effects on properties
      involving solid phases of different molecular compounds containing linear alkyl
      chains. The surprising results obtained for the ionic liquid series enabled us to
      unveil similar trends in the liquid phases of linear alkanes and alkanols via the
      application of a simple corresponding states principle. 

PMID- 24448217
TI  - Biomimetic virus-based colourimetric sensors.
AB  - Many materials in nature change colours in response to stimuli, making them
      attractive for use as sensor platform. However, both natural materials and their
      synthetic analogues lack selectivity towards specific chemicals, and introducing
      such selectivity remains a challenge. Here we report the self-assembly of
      genetically engineered viruses (M13 phage) into target-specific, colourimetric
      biosensors. The sensors are composed of phage-bundle nanostructures and exhibit
      viewing-angle independent colour, similar to collagen structures in turkey skin.
      On exposure to various volatile organic chemicals, the structures rapidly swell
      and undergo distinct colour changes. Furthermore, sensors composed of phage
      displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage
      display selectively distinguish TNT down to 300 p.p.b. over similarly structured
      chemicals. Our tunable, colourimetric sensors can be useful for the detection of
      a variety of harmful toxicants and pathogens to protect human health and national
      security.

PMID- 24448219
TI  - Pd/C-catalyzed direct formylation of aromatic iodides to aryl aldehydes using
      carbon dioxide as a C1 resource.
AB  - Pd/C-catalyzed direct formylation of aromatic iodides to aryl aldehydes using CO2
      as a C1 resource was realized for the first time in the presence of hydrosilanes
      and base DBU under mild conditions, giving a series of aldehydes in good yields. 

PMID- 24448220
TI  - Evidence of Epstein-Barr virus association with gastric cancer and non-atrophic
      gastritis.
AB  - Different lines of evidence support an association between Epstein-Barr virus
      (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is
      infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory
      response critical for progression from gastritis to GC. The role of EBV in early
      inflammatory gastric lesions has been poorly studied. A recent study proposed a
      cutoff value of 2000 EBV particles to identify patients with increased chances of
      infection of the gastric epithelium, which may favor the inflammatory process. To
      better understand the role of EBV in cancer progression, we analyzed 75 samples
      of GC, 147 control samples of non-tumor gastric tissue derived from GC patients
      and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round
      PCR was used for EBV detection in tumor and non-tumor controls and a more
      sensitive nested PCR for gastritis samples; both PCRs had lower detection limits
      above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non
      tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ
      hybridization showed EBV infection of epithelial cells in GC and in a third of
      NAG samples, while in the other NAGs infection was restricted to the mononuclear
      cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns,
      while these rare patterns were not observed in EBV negative samples. Our results
      support a role for EBV in GC and early precursor lesions, either as directly
      oncogenic infecting epithelial cells or indirectly as an inflammatory trigger. 

PMID- 24448221
TI  - Brd4-mediated nuclear retention of the papillomavirus E2 protein contributes to
      its stabilization in host cells.
AB  - Papillomavirus E2 is a multifunctional viral protein that regulates many aspects
      of the viral life cycle including viral episome maintenance, transcriptional
      activation, and repression. E2 is degraded by the ubiquitin-proteasome pathway.
      Cellular bromodomain protein Brd4 has been implicated in the stabilization of the
      E2 protein. E2 normally shuttles between the cytoplasm and the nucleus. In this
      study, we demonstrate that E2 ubiquitylation mostly occurs in the cytoplasm. We
      also find that the interaction with Brd4 promotes nuclear retention of
      papillomavirus E2 proteins and contributes to their stabilization in the nucleus.
      Compared to wild type E2 proteins, nuclear-localization-defective mutants are
      rapidly degraded by the ubiquitin-proteasome pathway; however, co-expression of
      Brd4 redirects these mutants into the nucleus and significantly increases their
      stability. We further demonstrate that tethering E2 proteins to chromatin as
      either double-bromodomain fusion proteins or histone 2B (H2B) fusion proteins
      significantly stabilizes the E2 proteins. Our studies suggest that chromatin
      recruitment of the E2 protein via interaction with Brd4 prevents E2
      ubiquitylation and proteasomal degradation in the cytoplasm, leading to its
      stabilization in the nucleus. These studies bring new insights for understanding
      Brd4-mediated E2 stabilization, and provide an additional mechanism by which the
      chromatin-associated Brd4 regulates E2 functions. 

PMID- 24448223
TI  - Do Inhibitory Control Demands Affect Event-Based Prospective Memory Performance
      in ADHD?
AB  - Objective: Empirical evidence on prospective memory (PM) in ADHD is inconsistent.
      Differential findings have been related to differential executive control
      demands. This study aimed at exploring the impact of inhibitory control on event
      based PM performance in ADHD. Method: Eighteen adults with ADHD and 18 controls
      performed a word categorization task with an embedded event-based PM task. In
      addition, participants performed an acoustically presented task that put either
      low or high loads on inhibitory control processes. Results: Inhibitory load did
      not differentially affect PM performance: Across both inhibitory load conditions,
      individuals with ADHD showed reduced PM performance when compared with controls.
      Moreover, inhibitory load did not influence PM performance across both groups.
      Conclusion: Possibly, full inhibitory control resources are not necessary during
      the entire duration of an event-based PM task, but may suffice to be employed
      after cue detection when needing to interrupt the ongoing task. (J. of Att. Dis.
      2013; XX(X) 1-XX).

PMID- 24448222
TI  - Feasibility of School-Based ADHD Interventions: A Mixed-Methods Study of
      Perceptions of Adolescents and Adults.
AB  - OBJECTIVE: Little is known about perceptions surrounding academic interventions
      for ADHD that determine intervention feasibility. METHOD: As part of a
      longitudinal mixed-methods research project, representative school district
      samples of 148 adolescents (54.8%), 161 parents (59.4%), 122 teachers (50.0%), 46
      health care providers (53.5%), and 92 school health professionals (65.7%)
      completed a cross-sectional survey. They also answered open-ended questions
      addressing undesirable intervention effects, which were analyzed using grounded
      theory methods. RESULTS: Adolescents expressed significantly lower receptivity
      toward academic interventions than adult respondents. Stigma emerged as a
      significant threat to ADHD intervention feasibility, as did perceptions that
      individualized interventions foster inequality. CONCLUSION: Findings suggest that
      adolescents' viewpoints must be included in intervention development to enhance
      feasibility and avoid interventions acceptable to adults, but resisted by
      adolescents.

PMID- 24448224
TI  - Neuropsychological Profiles on the WAIS-IV of Adults With ADHD.
AB  - OBJECTIVE: The aim of the study was to investigate the pattern of
      neuropsychological profiles on the Wechsler Adult Intelligence Scale-IV (WAIS-IV)
      for adults With ADHD relative to randomly matched controls and to assess overall
      intellectual ability discrepancies of the Full Scale Intelligence Quotient (FSIQ)
      and the General Ability Index (GAI). METHOD: In all, 116 adults With ADHD and 116
      controls between 16 and 71 years were assessed. RESULTS: Relative to controls,
      adults With ADHD show significant decrements in subtests with working memory and
      processing speed demands with moderate to large effect sizes and a higher GAI in
      comparison with the FSIQ. CONCLUSION: This suggests first that deficits
      identified with previous WAIS versions are robust in adults With ADHD and remain
      deficient when assessed with the WAIS-IV; second that the WAIS-IV reliably
      differentiates between patients and controls; and third that a reduction of the
      FSIQ is most likely due to a decrement in working memory and processing speed
      abilities. The findings have essential implications for the diagnostic process.

PMID- 24448225
TI  - Plasmonic nanostructures to enhance catalytic performance of zeolites under
      visible light.
AB  - Light absorption efficiency of heterogeneous catalysts has restricted their
      photocatalytic capability for commercially important organic synthesis. Here, we
      report a way of harvesting visible light efficiently to boost zeolite catalysis
      by means of plasmonic gold nanoparticles (Au-NPs) supported on zeolites. Zeolites
      possess strong Bronsted acids and polarized electric fields created by extra
      framework cations. The polarized electric fields can be further intensified by
      the electric near-field enhancement of Au-NPs, which results from the localized
      surface plasmon resonance (LSPR) upon visible light irradiation. The
      acetalization reaction was selected as a showcase performed on MZSM-5 and Au/MZSM
      5 (M = H(+), Na(+), Ca(2+), or La(3+)). The density functional theory (DFT)
      calculations confirmed that the intensified polarized electric fields played a
      critical role in stretching the C = O bond of the reactants of benzaldehyde to
      enlarge their molecular polarities, thus allowing reactants to be activated more
      efficiently by catalytic centers so as to boost the reaction rates. This
      discovery should evoke intensive research interest on plasmonic metals and
      diverse zeolites with an aim to take advantage of sunlight for plasmonic devices,
      molecular electronics, energy storage, and catalysis. 

PMID- 24448226
TI  - Beyond greyscale IVUS assessment of progression/regression: it should be simple,
      but it's not.

PMID- 24448227
TI  - Long-term effects of maximally intensive statin therapy on changes in coronary
      atheroma composition: insights from SATURN.
AB  - AIMS: To evaluate the effect of long-term maximally intensive statin therapy on
      indices of coronary atheroma composition in a randomized trial, and how these
      changes relate to modifications of serum lipoproteins and systemic inflammation.
      METHODS AND RESULTS: The Study of coronary Atheroma by inTravascular Ultrasound:
      the effect of Rosuvastatin vs. atorvastatiN (SATURN) employed serial
      intravascular ultrasound (IVUS) measures of coronary atheroma in patients treated
      with rosuvastatin 40 mg or atorvastatin 80 mg daily for 24 months. Seventy-one
      patients underwent serial assessment of indices of plaque composition by spectral
      analysis of the radiofrequency IVUS signal. Changes in low-density lipoprotein
      cholesterol [LDL-C; -52 (-72, -33) mg/dL, P < 0.001], C-reactive protein [CRP 
      0.2 (-1, 0.1) mg/L, P = 0.01], and high-density lipoprotein cholesterol [HDL-C;
      +2.8 (-0.3, 7.8) mg/dL, P < 0.001] were associated with regression of percent
      atheroma volume (PAV: -1.6 +/- 3.6%, P < 0.001). A reduction in estimated fibro
      fatty tissue volume accompanied atheroma regression (P < 0.001), while dense
      calcium tissue volume increased (P = 0.002). There were no changes in fibrous or
      necrotic core tissue volumes. Volumetric changes in necrotic core tissue
      correlated with on-treatment HDL-C (r = -0.27, P = 0.03) and CRP (r = 0.25, P =
      0.03) levels. A per-lesion analysis showed a reduction in the number of
      pathological intimal thickening lesions (defined by >=3 consecutive IVUS frames
      containing PAV of >=40%, predominantly fibro-fatty plaque, with <10% confluent
      necrotic core and <10% confluent dense calcium) at follow-up (67 vs. 38, P =
      0.001). Fibroatheromas and fibrotic lesions remained static in number.
      CONCLUSIONS: Changes in indices of atheroma composition accompany regression of
      coronary atheroma with maximally intensive statin therapy, and associate with
      anti-inflammatory effects of statins. CLINICALTRAILSGOV NUMBER: NCT000620542.

PMID- 24448229
TI  - A spectroscopic study on the formation of Cm(III) acetate complexes at elevated
      temperatures.
AB  - The complexation of Cm(III) with acetate is studied by time resolved laser
      fluorescence spectroscopy (TRLFS) as a function of ionic strength, ligand
      concentration, temperature and background electrolyte (NaClO4, NaCl and CaCl2
      solution). The speciation of Cm(III) is determined by peak deconvolution of the
      emission spectra. To obtain the thermodynamic stability constants (log K) for the
      formation of [Cm(Ac)n](3-n) (n = 1-3), the experimental data are extrapolated to
      zero ionic strength according to the specific ion interaction theory (SIT). The
      results show a continuous increase of the stability constants with increasing
      temperature (20-90  degrees C). The standard reaction enthalpies and entropies
      (DeltarH, DeltarS) of the respective reactions are derived from the integrated
      Van't Hoff equation. The results show that all complexation steps are endothermic
      and thus entropy driven (DeltarH and DeltarS > 0).

PMID- 24448228
TI  - Left main trunk connecting to superior vena cava via aneurysmal coronary artery
      fistula.

PMID- 24448231
TI  - There are still problems in identifying who will develop complications of sore
      throat in primary care.

PMID- 24448230
TI  - Duplex formation between the sRNA DsrA and rpoS mRNA is not sufficient for
      efficient RpoS synthesis at low temperature.
AB  - At low temperatures the Escherichia coli rpoS mRNA, encoding the stationary phase
      sigma factor RpoS, forms an intramolecular secondary structure (iss) that impedes
      translation initiation. Under these conditions the small RNA DsrA, which is
      stabilzed by Hfq, forms a duplex with rpoS mRNA sequences opposite of the
      ribosome-binding site (rbs). Both the DEAD box helicase CsdA and Hfq have been
      implicated in DsrA.rpoS duplex formation. Hfq binding to A-rich sequences in the
      rpoS leader has been suggested to restructure the mRNA, and thereby to accelerate
      DsrA.rpoS duplex formation, which, in turn, was deemed to free the rpoS rbs and
      to permit ribosome loading on the mRNA. Several experiments designed to elucidate
      the role of Hfq in DsrA-mediated translational activation of rpoS mRNA have been
      conducted in vitro. Here, we assessed RpoS synthesis in vivo to further study the
      role of Hfq in rpoS regulation. We show that RpoS synthesis was reduced when DsrA
      was ectopically overexpressed at 24  degrees C in the absence of Hfq despite of
      DsrA.rpoS duplex formation. This observation indicated that DsrA.rpoS annealing
      may not be sufficient for efficient ribosome loading on rpoS mRNA. In addition, a
      HfqG29A mutant protein was employed, which is deficient in binding to A-rich
      sequences present in the rpoS leader but proficient in DsrA binding. We show that
      DsrA.rpoS duplex formation occurs in the presence of the HfqG29A mutant protein
      at low temperature, whereas synthesis of RpoS was greatly diminished. RNase T1
      footprinting studies of DsrA.rpoS duplexes in the absence and presence of Hfq or
      HfqG29A indicated that Hfq is required to resolve a stem-loop structure in the
      immediate coding region of rpoS mRNA. These in vivo studies corroborate the
      importance of the A-rich sequences in the rpoS leader and strongly suggest that
      Hfq, besides stabilizing DsrA and accelerating DsrA.rpoS duplex formation, is
      also required to convert the rpoS mRNA into a translationally competent form. 

PMID- 24448232
TI  - Metal-organic frameworks MIL-88A hexagonal microrods as a new photocatalyst for
      efficient decolorization of methylene blue dye.
AB  - Metal-organic frameworks (MOFs) MIL-88A hexagonal microrods as a new
      photocatalyst show an active performance for methylene blue (MB) dye
      decolorization using visible light. MB decolorization over the MIL-88A
      photocatalyst follows first-order kinetics. The addition of a H2O2 electron
      acceptor can markedly enhance the photocatalytic MB decoloration performance of
      MIL-88A. Moreover, MIL-88A showed a very stable activity for MB decoloration
      after four consecutive usages. Owing to the advantages of the visible light
      response, low cost and abundance in nature, this active MIL-88A MOF photocatalyst
      would have great potential for environmental purification. 

PMID- 24448233
TI  - The influence of the DeltaK280 mutation and N- or C-terminal extensions on the
      structure, dynamics, and fibril morphology of the tau R2 repeat.
AB  - Tau is a microtubule-associated protein and is involved in microtubule assembly
      and stabilization. It consists of four repeats that bind to the microtubule. The
      DeltaK280 deletion mutation in the tau R2 repeat region is directly associated
      with the development of the frontotemporal dementia parkinsonism linked to
      chromosome 17 (FTDP-17). This deletion mutation is known to accelerate tau R2
      repeat aggregation. However, the secondary and the tertiary structures of the
      self-assembled DeltaK280 tau R2 repeat mutant aggregates are still controversial.
      Moreover, it is unclear whether extensions by one residue in the N- or the C
      terminus of this mutant can influence the secondary or the tertiary structure.
      Herein, we combine solid-state NMR, atomic force microscopy, electron microscopy
      and all-atom explicit molecular dynamics simulations to investigate the effects
      of the deletion mutation and the N- and the C-terminal extension of this mutant
      on the structure. Our main findings show that the deletion mutation induces the
      formation of small aggregates, such as oligomers, and reduces the formation of
      fibrils. However, the extensions in the N- or the C-terminus revealed more fibril
      formation than small aggregates. Further, in the deletion mutation only one
      structure is preferred, while the N- and the C-terminal extensions strongly lead
      to polymorphic states. Finally, our broad and combined experimental and
      computational techniques provide direct structural information regarding
      DeltaK280 tau R2 repeat mutant aggregates and their extensions in the N- and C
      terminii by one residue. 

PMID- 24448234
TI  - Calculated computed tomography volumes of lacrimal glands and comparison to
      clinical findings in patients with thyroid eye disease.
AB  - PURPOSE: To describe the range of lacrimal gland volumes on CT in Caucasian
      patients with thyroid eye disease (TED) and to correlate with clinical findings.
      METHODS: With institutional review board approval, 125 orbital CT scans for TED
      were reviewed. OsiriX software was used to calculate the volume of the lacrimal
      gland. Comparison of the volumes was made with previously published results of
      the normal population. Patient race, gender, smoking status, diplopia, tearing,
      exophthalmometry, superficial punctate keratitis (SPK), lagophthalmos,
      restriction in motility, and VISA score were collected. RESULTS: The mean volume
      of the lacrimal gland in patients with TED was 0.890 cm in right orbits (standard
      deviation [SD] 0.348), 0.851 cm in left orbits (SD 0.350), with no significant
      difference between right and left (p = 0.311). The mean volume was 0.811 cm in
      right male orbits (SD 0.386) and 0.911 cm in right female orbits (SD 0.335), with
      no significant difference between men and women (p = 0.774). These findings were
      confirmed in an analysis of left orbits. The volume of right and left orbits
      correlated well (r = 0.777, p < 0.0001). The lacrimal gland volume in patients
      with TED was greater compared with the normal population using a 2-sample t test
      (p < 0.0001). Exophthalmometry (right: r = 0.225, p = 0.0115; left: r = 0.267, p
      = 0.0026) and subjective tearing (right: r = 0.226, p = 0.0138; left: r = 0.197,
      p = 0.0322) correlated with lacrimal gland volume. CONCLUSIONS: This study is the
      first to report the volume of the lacrimal gland calculated on CT scan for
      patients with TED. The lacrimal gland is larger in patients with TED and
      correlates with subjective tearing and exophthalmometry.

PMID- 24448235
TI  - Novel bispecific antibodies increase gammadelta T-cell cytotoxicity against
      pancreatic cancer cells.
AB  - The ability of human gammadelta T cells from healthy donors to kill pancreatic
      ductal adenocarcinoma (PDAC) in vitro and in vivo in immunocompromised mice
      requires the addition of gammadelta T-cell-stimulating antigens. In this study,
      we demonstrate that gammadelta T cells isolated from patients with PDAC tumor
      infiltrates lyse pancreatic tumor cells after selective stimulation with
      phosphorylated antigens. We determined the absolute numbers of gammadelta T-cell
      subsets in patient whole blood and applied a real-time cell analyzer to measure
      their cytotoxic effector function over prolonged time periods. Because
      phosphorylated antigens did not optimally enhance gammadelta T-cell cytotoxicity,
      we designed bispecific antibodies that bind CD3 or Vgamma9 on gammadelta T cells
      and Her2/neu (ERBB2) expressed by pancreatic tumor cells. Both antibodies
      enhanced gammadelta T-cell cytotoxicity with the Her2/Vgamma9 antibody also
      selectively enhancing release of granzyme B and perforin. Supporting these
      observations, adoptive transfer of gammadelta T cells with the Her2/Vgamma9
      antibody reduced growth of pancreatic tumors grafted into SCID-Beige
      immunocompromised mice. Taken together, our results show how bispecific
      antibodies that selectively recruit gammadelta T cells to tumor antigens
      expressed by cancer cells illustrate the tractable use of endogenous gammadelta T
      cells for immunotherapy.

PMID- 24448236
TI  - Axon guidance factor SLIT2 inhibits neural invasion and metastasis in pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) metastasizes by neural, vascular, and
      local invasion routes, which limit patient survival. In nerves and vessels, SLIT2
      and its ROBO receptors constitute repellent guidance cues that also direct
      epithelial branching. Thus, the SLIT2-ROBO system may represent a key pinch point
      to regulate PDAC spread. In this study, we examined the hypothesis that escaping
      from repellent SLIT2-ROBO signaling is essential to enable PDAC cells to
      appropriate their local stromal infrastructure for dissemination. Through
      immunohistochemical analysis, we detected SLIT2 receptors ROBO1 and ROBO4 on
      epithelia, nerves, and vessels in healthy pancreas and PDAC specimens,
      respectively. SLIT2 mRNA expression was reduced in PDAC compared with
      nontransformed pancreatic tissues and cell lines, suggesting a reduction in SLIT2
      ROBO pathway activity in PDAC. In support of this interpretation, restoring the
      SLIT2 expression in SLIT2-deficient PDAC cells inhibited their bidirectional
      chemoattraction with neural cells, and more specifically, impaired unidirectional
      PDAC cell navigation along outgrowing neurites in models of neural invasion.
      Restoring autocrine/paracrine SLIT2 signaling was also sufficient to inhibit the
      directed motility of PDAC cells, but not their random movement. Conversely, RNA
      interference-mediated silencing of ROBO1 stimulated the motility of SLIT2
      competent PDAC cells. Furthermore, culture supernatants from SLIT2-competent PDAC
      cells impaired migration of endothelial cells (human umbilical vein endothelial
      cells), whereas an N-terminal SLIT2 cleavage fragment stimulated such migration.
      In vivo investigations of pancreatic tumors with restored SLIT2 expression
      demonstrated reduced invasion, metastasis, and vascularization, with opposing
      effects produced by ROBO1 silencing in tumor cells or sequestration of endogenous
      SLIT2. Analysis of clinical specimens of PDAC showed that those with low SLIT2
      mRNA expression exhibited a higher incidence and a higher fraction of tumor
      infiltrated lymph nodes. Taken together, our findings argue that disrupting SLIT2
      ROBO signaling in PDAC may enhance metastasis and predispose PDAC cells to neural
      invasion.

PMID- 24448237
TI  - Genetic and phenotypic diversity in breast tumor metastases.
AB  - Metastatic disease is the main cause of cancer-related mortality due to almost
      universal therapeutic resistance. Despite its high clinical relevance, our
      knowledge of how cancer cell populations change during metastatic progression is
      limited. Here, we investigated intratumor genetic and phenotypic heterogeneity
      during metastatic progression of breast cancer. We analyzed cellular genotypes
      and phenotypes at the single cell level by performing immunoFISH in intact tissue
      sections of distant metastatic tumors from rapid autopsy cases and from primary
      tumors and matched lymph node metastases collected before systemic therapy. We
      calculated the Shannon index of intratumor diversity in all cancer cells and
      within phenotypically distinct cell populations. We found that the extent of
      intratumor genetic diversity was similar regardless of the chromosomal region
      analyzed, implying that it may reflect an inherent property of the tumors. We
      observed that genetic diversity was highest in distant metastases and was
      generally concordant across lesions within the same patient, whereas treatment
      naive primary tumors and matched lymph node metastases were frequently
      genetically more divergent. In contrast, cellular phenotypes were more discordant
      between distant metastases than primary tumors and matched lymph node metastases.
      Diversity for 8q24 was consistently higher in HER2(+) tumors compared with other
      subtypes and in metastases of triple-negative tumors relative to primary sites.
      We conclude that our integrative method that couples ecologic models with
      experimental data in human tissue samples could be used for the improved
      prognostication of patients with cancer and for the design of more effective
      therapies for progressive disease.

PMID- 24448238
TI  - BRCA2 phosphorylated by PLK1 moves to the midbody to regulate cytokinesis
      mediated by nonmuscle myosin IIC.
AB  - Cytokinesis is the critical final step in cell division. BRCA2 disruption during
      cytokinesis is associated with chromosome instability, but mechanistic
      information is lacking that could be used to prevent cancer cell division. In
      this study, we report that BRCA2 phosphorylation by the mitotic polo-like kinase
      (PLK1) governs the localization of BRCA2 to the Flemming body at the central
      midbody, permitting an interaction with nonmuscle myosin IIC (NM-IIC). Formation
      of an NM-IIC ring-like structure at the Flemming body shows that the IIC-ring
      relies on its ATPase activity stimulated by interaction with BRCA2 and associated
      proteins. Notably, inhibiting this binding inactivated the ATPase activity,
      causing disassembly of the IIC-ring, defective formation of the midbody, and
      interruption of cytokinesis. An analysis of cancer-associated mutations in BRCA2
      at the PLK1-binding site suggests that they may contribute to cytokinetic defects
      by altering BRCA2 localization. Our findings suggest that BRCA2-dependent IIC
      ring formation is a critical step in proper formation of the midbody, offering an
      explanation for how chromosome instability may arise in breast cancer.

PMID- 24448239
TI  - MET signaling in colon cancer stem-like cells blunts the therapeutic response to
      EGFR inhibitors.
AB  - Metastatic colorectal cancer remains largely incurable, although in a subset of
      patients, survival is prolonged by new targeting agents such as anti-EGF receptor
      (anti-EGFR) antibodies. This disease is believed to be supported by a
      subpopulation of stem-like cells termed colon cancer-initiating cell (CCIC),
      which may also confer therapeutic resistance. However, how CCICs respond to EGFR
      inhibition has not been fully characterized. To explore this question, we
      systematically generated CCICs through spheroid cultures of patient-derived
      xenografts of metastatic colorectal cancer. These cultures, termed "xenospheres,"
      were capable of long-term self-propagation in vitro and phenocopied the original
      patient tumors in vivo, thus operationally defining CCICs. Xenosphere CCICs
      retained the genetic determinants for EGFR therapeutic response in vitro and in
      xenografts; like the original tumors, xenospheres harboring a mutated KRAS gene
      were resistant to EGFR therapy, whereas those harboring wild-type RAS pathway
      genes (RAS(wt)) were sensitive. Notably, the effects of EGFR inhibition in
      sensitive CCICs could be counteracted by cytokines secreted by cancer-associated
      fibroblasts. In particular, we found that the MET receptor ligand hepatocyte
      growth factor (HGF) was especially active in supporting in vitro CCIC
      proliferation and resistance to EGFR inhibition. Ectopic production of human HGF
      in CCIC xenografts rendered the xenografts susceptible to MET inhibition, which
      sensitized the response to EGFR therapy. By showing that RAS(wt) CCICs rely on
      both EGFR and MET signaling, our results offer a strong preclinical proof-of
      concept for concurrent targeting of these two pathways in the clinical setting.

PMID- 24448240
TI  - Fragmented sleep accelerates tumor growth and progression through recruitment of
      tumor-associated macrophages and TLR4 signaling.
AB  - Sleep fragmentation (SF) is a highly prevalent condition and a hallmark of sleep
      apnea, a condition that has been associated with increased cancer incidence and
      mortality. In this study, we examined the hypothesis that sleep fragmentation
      promotes tumor growth and progression through proinflammatory TLR4 signaling. In
      the design, we compared mice that were exposed to sleep fragmentation one week
      before engraftment of syngeneic TC1 or LL3 tumor cells and tumor analysis four
      weeks later. We also compared host contributions through the use of mice
      genetically deficient in TLR4 or its effector molecules MYD88 or TRIF. We found
      that sleep fragmentation enhanced tumor size and weight compared with control
      mice. Increased invasiveness was apparent in sleep fragmentation tumors, which
      penetrated the tumor capsule into surrounding tissues, including adjacent muscle.
      Tumor-associated macrophages (TAM) were more numerous in sleep fragmentation
      tumors, where they were distributed in a relatively closer proximity to the tumor
      capsule compared with control mice. Although tumors were generally smaller in
      both MYD88(-/-) and TRIF(-/-) hosts, the more aggressive features produced by
      sleep fragmentation persisted. In contrast, these more aggressive features
      produced by sleep fragmentation were abolished completely in TLR4(-/-) mice. Our
      findings offer mechanistic insights into how sleep perturbations can accelerate
      tumor growth and invasiveness through TAM recruitment and TLR4 signaling
      pathways.

PMID- 24448241
TI  - HDAC2 provides a critical support to malignant progression of hepatocellular
      carcinoma through feedback control of mTORC1 and AKT.
AB  - Aberrant regulation of histone deacetylase 2 (HDAC2) contributes to malignant
      progression in various cancers, but the underlying mechanism leading to the
      activation of oncogenic HDAC2 remains unknown. In this study, we show that HDAC2
      expression is upregulated in a large cohort of patients with human hepatocellular
      carcinoma, and that high expression of HDAC2 was significantly associated with
      poor prognosis of patients with hepatocellular carcinoma. We found that mTORC1/NF
      kappaBp50 signaling is necessary for the growth factor-induced HDAC2 and is
      sustained in hepatocellular carcinoma, but not in normal hepatic cells. Growth
      factor-induced mTORC1 activates the nuclear translocation of NF-kappaBp50, where
      it binds to the intragenic sequences of the HDAC2 gene and promotes its
      transcription. Hepatocellular carcinoma tissues derived from chemical-induced
      mouse and rat liver cancer models validated that mTORC1 activation and NF
      kappaBp50 nuclear translocation are essential for the transcriptional activation
      of oncogenic HDAC2 in hepatocellular carcinoma. In addition, we demonstrate that
      HDAC2 is required to maintain mTORC1 activity by stabilizing the mTOR/RAPTOR
      complex. Elevated expression of HDAC2 triggers a positive feedback loop that
      activates AKT phosphorylation via the transcriptional modulation of
      phosphoinositide signaling molecules. Bioinformatics analysis of HDAC2 signature
      and immunoblot analysis of mesenchymal genes also evidenced that HDAC2 plays a
      role in the malignant behavior of tumor cells by Snail induction and
      simultaneously E-cadherin suppression in hepatocellular carcinoma cells. These
      findings establish a molecular mechanism responsible for the activation of
      oncogenic HDAC2, which explains how growth factor-induced HDAC2 maintains
      mitogenic signaling and function during hepatocellular malignant progression and
      provide a novel strategy for therapeutic intervention in liver cancer. Cancer
      Res; 74(6); 1728-38. (c)2014 AACR. 

PMID- 24448242
TI  - Alarmin IL-33 acts as an immunoadjuvant to enhance antigen-specific tumor
      immunity.
AB  - Studies of interleukin (IL)-33 reveal a number of pleiotropic properties. Here,
      we report that IL-33 has immunoadjuvant effects in a human papilloma virus (HPV)
      associated model for cancer immunotherapy where cell-mediated immunity is
      critical for protection. Two biologically active isoforms of IL-33 exist that are
      full-length or mature, but the ability of either isoform to function as a vaccine
      adjuvant that influences CD4 T helper 1 or CD8 T-cell immune responses is not
      defined. We showed that both IL-33 isoforms are capable of enhancing potent
      antigen-specific effector and memory T-cell immunity in vivo in a DNA vaccine
      setting. In addition, although both IL-33 isoforms drove robust IFN-gamma
      responses, neither elevated secretion of IL-4 or immunoglobulin E levels.
      Further, both isoforms augmented vaccine-induced antigen-specific polyfunctional
      CD4(+) and CD8(+) T-cell responses, with a large proportion of CD8(+) T cells
      undergoing plurifunctional cytolytic degranulation. Therapeutic studies indicated
      that vaccination with either IL-33 isoform in conjunction with an HPV DNA vaccine
      caused rapid and complete regressions in vivo. Moreover, IL-33 could expand the
      magnitude of antigen-specific CD8(+) T-cell responses and elicit effector-memory
      CD8(+) T cells. Taken together, our results support the development of these IL
      33 isoforms as immunoadjuvants in vaccinations against pathogens, including in
      the context of antitumor immunotherapy.

PMID- 24448243
TI  - FoxO transcription factors promote AKT Ser473 phosphorylation and renal tumor
      growth in response to pharmacologic inhibition of the PI3K-AKT pathway.
AB  - The PI3K-AKT pathway is hyperactivated in many human cancers, and several drugs
      to inhibit this pathway, including the PI3K/mTOR dual inhibitor NVP-BEZ235, are
      currently being tested in various preclinical and clinical trials. It has been
      shown that pharmacologic inhibition of the PI3K-AKT pathway results in feedback
      activation of other oncogenic signaling pathways, which likely will limit the
      clinical utilization of these inhibitors in cancer treatment. However, the
      underlying mechanisms of such feedback regulation remain incompletely understood.
      The PI3K-AKT pathway is a validated therapeutic target in renal cell carcinoma
      (RCC). Here, we show that FoxO transcription factors serve to promote AKT
      phosphorylation at Ser473 in response to NVP-BEZ235 treatment in renal cancer
      cells. Inactivation of FoxO attenuated NVP-BEZ235-induced AKT Ser473
      phosphorylation and rendered renal cancer cells more susceptible to NVP-BEZ235
      mediated cell growth suppression in vitro and tumor shrinkage in vivo.
      Mechanistically, we showed that FoxOs upregulated the expression of Rictor, an
      essential component of MTOR complex 2, in response to NVP-BEZ235 treatment and
      revealed that Rictor is a key downstream target of FoxOs in NVP-BEZ235-mediated
      feedback regulation. Finally, we show that FoxOs similarly modulate the feedback
      response on AKT Ser473 phosphorylation and renal tumor growth by other
      phosphoinositide 3-kinase (PI3K) or AKT inhibitor treatment. Together, our study
      reveals a novel mechanism of PI3K-AKT inhibition-mediated feedback regulation and
      may identify FoxO as a novel biomarker to stratify patients with RCC for PI3K or
      AKT inhibitor treatment, or a novel therapeutic target to synergize with PI3K-AKT
      inhibition in RCC treatment.

PMID- 24448244
TI  - Neuroplastic changes occur early in the development of pancreatic ductal
      adenocarcinoma.
AB  - Perineural tumor invasion of intrapancreatic nerves, neurogenic inflammation, and
      tumor metastases along extrapancreatic nerves are key features of pancreatic
      malignancies. Animal studies show that chronic pancreatic inflammation produces
      hypertrophy and hypersensitivity of pancreatic afferents and that sensory fibers
      may themselves drive inflammation via neurogenic mechanisms. Although genetic
      mutations are required for cancer development, inflammation has been shown to be
      a precipitating event that can accelerate the transition of precancerous lesions
      to cancer. These observations led us to hypothesize that inflammation that
      accompanies early phases of pancreatic ductal adenocarcinoma (PDAC) would produce
      pathologic changes in pancreatic neurons and innervation. Using a lineage-labeled
      genetically engineered mouse model of PDAC, we found that pancreatic neurotrophic
      factor mRNA expression and sensory innervation increased dramatically when only
      pancreatic intraepithelial neoplasia were apparent. These changes correlated with
      pain-related decreases in exploratory behavior and increased expression of
      nociceptive genes in sensory ganglia. At later stages, cells of pancreatic origin
      could be found in the celiac and sensory ganglia along with metastases to the
      spinal cord. These results demonstrate that the nervous system participates in
      all stages of PDAC, including those that precede the appearance of cancer.

PMID- 24448245
TI  - Universal marker and detection tool for human sarcoma circulating tumor cells.
AB  - To date, no specific marker exists for the detection of circulating tumor cells
      (CTC) from different types of sarcomas, though tools are available for detection
      of CTCs in peripheral blood of patients with cancer for epithelial cancers. Here,
      we report cell-surface vimentin (CSV) as an exclusive marker on sarcoma CTC
      regardless of the tissue origin of the sarcoma as detected by a novel monoclonal
      antibody. Utilizing CSV as a probe, we isolated and enumerated sarcoma CTCs with
      high sensitivity and specificity from the blood of patients bearing different
      types of sarcoma, validating their phenotype by single cell genomic
      amplification, mutation detection, and FISH. Our results establish the first
      universal and specific CTC marker described for enumerating CTCs from different
      types of sarcoma, thereby providing a key prognosis tool to monitor cancer
      metastasis and relapse.

PMID- 24448246
TI  - Training ophthalmologists for developing economies: an African-German
      partnership.

PMID- 24448247
TI  - Republished: unlocking the potential: longitudinal audit finds multifaceted
      education for general practice increases HIV testing and diagnosis.
AB  - BACKGROUND: This longitudinal study aimed to evaluate the impact of a
      multifaceted educational intervention (Sexual Health in Practice, SHIP) on
      general practice HIV testing rates in a high prevalence London area.
      INTERVENTION: SHIP offered training in sexual health clinical skills to general
      practitioners (GPs) and practice nurses (PNs) in Haringey. SHIP training aims to
      break down stigma in sexual health and provide sexual history and communication
      tools (e.g. differential diagnosis), and provides resources to practices
      (including condoms). DESIGN: Numbers of GP HIV tests were collected from
      laboratories for 24 months prior, 19 months during and 5 months after training.
      Attendance data and practice list sizes were obtained. RESULTS: 39 of 51
      practices had at least one trained individual. These 'trained' practices
      conducted an average 526 HIV tests p.a. before training began which rose to a
      projected 1556 p.a. (on the basis of the last 6 months of data). Testing rates of
      trained and untrained practices increased from 2.29 to 6.66 and 1.54 to 1.90
      tests/1000 registered patients/year (p=0.0016 and p=0.5195) respectively. The
      rate of positive diagnosis was high in the trained group (18.0 and 16.7
      positives/1000 tests before and after training began; p=0.7908). This equates to
      a rise from 9.5 to 22 new diagnoses p.a. CONCLUSIONS: The training intervention
      has been found to significantly increase general practice HIV testing rates in
      the absence of financial incentives. Positivity rates are substantially higher
      than that found in pilots of screening in London, suggesting that the training
      nurtured and supplemented complex clinical skills.

PMID- 24448248
TI  - Republished: the role of amyloid beta in the pathogenesis of Alzheimer's disease.
AB  - The amyloid-beta peptide (Abeta) is widely considered to be the major toxic agent
      in the pathogenesis of Alzheimer's disease, a condition which afflicts
      approximately 36 million people worldwide. Despite a plethora of studies
      stretching back over two decades, identifying the toxic Abeta species has proved
      difficult. Debate has centred on the Abeta fibril and oligomer. Despite support
      from numerous experimental models, important questions linger regarding the role
      of the Abeta oligomer in particular. It is likely a huge array of oligomers,
      rather than a single species, which cause toxicity. Reappraisal of the role of
      the Abeta fibril points towards a dynamic relationship with the Abeta oligomer
      within an integrated system, as supported by evidence from microglia. However,
      some continue to doubt the pathological role of amyloid beta, instead proposing a
      protective role. If the field is to progress, all Abeta oligomers should be
      characterised, the nomenclature revised and a consistent experimental protocol
      defined. For this to occur, collaboration will be required between major research
      groups and innovative analytical tools developed. Such action must surely be
      taken if amyloid-based therapeutic endeavour is to progress. 

PMID- 24448249
TI  - Good questions.

PMID- 24448250
TI  - Graphene etching on SiC grains as a path to interstellar polycyclic aromatic
      hydrocarbons formation.
AB  - Polycyclic aromatic hydrocarbons as well as other organic molecules appear among
      the most abundant observed species in interstellar space and are key molecules to
      understanding the prebiotic roots of life. However, their existence and abundance
      in space remain a puzzle. Here we present a new top-down route to form polycyclic
      aromatic hydrocarbons in large quantities in space. We show that aromatic species
      can be efficiently formed on the graphitized surface of the abundant silicon
      carbide stardust on exposure to atomic hydrogen under pressure and temperature
      conditions analogous to those of the interstellar medium. To this aim, we mimic
      the circumstellar environment using ultra-high vacuum chambers and investigate
      the SiC surface by in situ advanced characterization techniques combined with
      first-principles molecular dynamics calculations. These results suggest that top
      down routes are crucial to astrochemistry to explain the abundance of organic
      species and to uncover the origin of unidentified infrared emission features from
      advanced observations. 

PMID- 24448251
TI  - Dissolution of the metal sensitizers Ni, Be, Cr in artificial sweat to improve
      estimates of dermal bioaccessibility.
AB  - Dermal exposure to sensitizing metals is a serious occupational and public health
      problem. The usual approach to dermal exposure assessment is to process samples
      by chemical methods that use reactants to digest the metal particles and quantify
      the mass. In the case of dermal exposure assessment, these reactants are not
      representative of the skin surface film liquids and hence, may overestimate
      bioaccessibility. We hypothesize that the amount and form of sensitizer on a
      sample that leaches in a biological fluid, as can be estimated using artificial
      sweat, may be a more relevant metric for assessing health risks. Beryllium metal
      (Be), nickel metal (Ni), and chromium carbide (Cr3C2) particles were
      characterized and masses of sensitizing ions were measured using established
      reactant-assisted digestion procedures and extraction in artificial sweat under
      physiologically relevant conditions. Chromium ions released into artificial sweat
      were speciated to understand valence states. The ratios of the fraction of metal
      dissolved in artificial sweat relative to that dissolved by chemical-specific
      reactants were 1/2 (Be), 1/108 (Ni), and 1/2500 (Cr). The divalent Be and Ni
      cations were stable in artificial sweat over time (did not precipitate) whereas
      hexavalent chromium [Cr(VI)] ions decayed over time. Further analysis using
      speciated isotope dilution mass spectrometry revealed that the decay of Cr(VI)
      was accompanied by the formation of Cr(III) in the sweat model. Use of reactant
      assisted analytical chemistry to quantify amounts of metal sensitizers on samples
      could overestimate biologically relevant exposure. In addition to mass, the
      valence state also influences penetration through the outer stratum corneum of
      the skin and is an important consideration when assessing exposure to complex
      sensitizers such as Cr which have multiple valence states with differing
      penetration efficiencies.

PMID- 24448252
TI  - Divergent effects of various diabetes drugs on cardiovascular prognosis.
AB  - This review discusses the current data on various antidiabetic medications and
      their effects on major adverse cardiovascular events (MACE). Diabetes mellitus is
      a potent independent risk factor for MACE, and this risk increases in proportion
      to the elevation of hemoglobin A1c. Available data suggest that tight glycemic
      control in patients with diabetes reduces microvascular complications, but has
      limited effect or may even increase the risk of MACE and other macrovascular
      complications. For individuals with type 2 diabetes mellitus (T2DM) drugs that
      reduce postprandial glucose (alpha-glucosidase inhibitors, incretin mimetics,
      quick-acting bromocriptine, dipeptidyl peptidase-4 inhibitors, and colesevelam)
      are associated with a decrease in MACE. Drugs that directly reduce insulin
      resistance (pioglitazone and metformin) are also associated with lesser but still
      significant decreases in MACE. Insulin, rosiglitazone (but not pioglitazone), and
      sulfonylureas (especially with glyburide and particularly the glyburide +
      metformin combination) are associated with increases in MACE. In summary, drugs
      that reduce postprandial glucose and improve insulin resistance without
      predisposing patients to hypoglycemia appear to both control hyperglycemia and
      improve cardiovascular prognosis. However, many of the traditional agents used
      for treating T2DM, such as insulin and sulfonylureas, do not improve
      cardiovascular prognosis despite improving hyperglycemia. 

PMID- 24448253
TI  - The role of early and sufficient isolated venovenous ultrafiltration in heart
      failure patients with pulmonary and systemic congestion.
AB  - Hypervolemia, present in at least 70% of patients with decompensated heart
      failure, results in renal dysfunction due to increased renal venous pressure,
      impaired renal autoregulation, and decreased renal blood flow that are associated
      with increased morbidity and mortality. Loop diuretics, widely used in congested
      patients, result in the production of hypotonic urine and neurohormonal
      activation. In contrast, ultrafiltration (UF) removes isotonic fluid without
      increasing renin secretion by the macula densa. Simplified devices that permit us
      to perform UF with peripheral venous access, adjustable blood flows, and small
      extracorporeal blood volumes make this therapy feasible at most hospitals and in
      less acute care settings. Conflicting results on the effects of UF in heart
      failure patients underscore the challenges of patient selection and choice of
      fluid removal rates. Unfavorable outcomes in patients undergoing UF in the midst
      of cardiorenal syndrome type 1 are in contrast with the sustained benefits of UF
      initiated before unsuccessful use of high-dose intravenous (IV) diuretics. UF
      rates should be based on a precise knowledge of the degree of hypervolemia and
      careful assessment of blood volume changes, so that extracellular fluid gradually
      refills the intravascular space and volume depletion is avoided. Poor outcomes
      are likely to occur if fluid removal rates are not tailored to individual
      patients' clinical characteristics. A large trial is ongoing to determine if a
      strategy of early UF, initiated before renal function is worsened by other
      therapies, is superior to IV diuretics in reducing 90-day heart-failure-related
      hospitalizations in patients with pulmonary and systemic congestion. 

PMID- 24448254
TI  - Choosing wisely.

PMID- 24448255
TI  - Contemporary diagnosis of carotid fibromuscular dysplasia: role of power Doppler
      and a review of other diagnostic modalities.
AB  - Fibromuscular dysplasia (FMD) is a nonatheromatous, noninflammatory arteriopathy
      with segmental involvement of medium-sized arteries in multiple vascular beds. It
      most commonly involves the renal and carotid arteries. The etiology is unknown,
      although various hormonal and mechanical factors have been suggested. The disease
      can occur at any age but is usually diagnosed in middle-aged individuals,
      predominantly women. FMD is much more common than previously thought, perhaps
      affecting as many as 4% of adult women. Clinical manifestations of the internal
      carotid artery involvement are transitory ischemic attacks or cerebral
      infarction, as well as nonspecific symptoms such as headache and vertigo. In
      cases of cerebrovascular events, endovascular or surgical treatment is
      recommended; therefore, detection of FMD is of considerable importance. The gold
      standard for diagnosing FMD is catheter angiography (with the classic "string of
      beads" pattern), but this invasive procedure is only used for patients in whom it
      is clinically pertinent to proceed with revascularization. The optimal
      noninvasive modality for diagnosis and quantification for FMD is not known and
      little information has been recently published about new diagnostic modalities.
      Although angiography, computed tomography angiography, and magnetic resonance
      angiography are excellent in confirming the morphologic diagnosis of FMD, they
      are less accurate in assessing the hemodynamic significance of the lesions.
      Ultrasonography is useful in assessing the degree of carotid artery stenosis. Use
      of power Doppler ultrasound improves the ability to detect the morphologic
      features of carotid FMD. 

PMID- 24448256
TI  - The use of percutaneous left ventricular assist device in high-risk percutaneous
      coronary intervention and cardiogenic shock.
AB  - Patients with high-risk coronary lesions may be denied coronary artery bypass
      grafting due to excessive comorbidities. Percutaneous coronary intervention (PCI)
      may be a feasible revascularization strategy in high-risk patients who present
      with ST-elevation myocardial infarction and cardiogenic shock. Historically, the
      use if intra-aortic balloon pump (IABP) has been used in high-risk PCI and
      cardiogenic shock. However, recent data has shown that elective IABP insertion
      did not reduce the incidence of major cardiovascular events following PCI. The
      use of a left ventricular assist device is a reasonable and safe alternative
      compared with IABP counterpulsation, giving greater cardiac output and
      hemodynamic support in patients undergoing high-risk PCI and in those with severe
      cardiogenic shock. This review outlines a case of severe cardiogenic shock and
      hemodynamic instability where high-risk PCI is a reasonable option. 

PMID- 24448257
TI  - Cardiometabolic risk factors and atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia worldwide; it is a
      significant risk factor for stroke and embolization, and has an impact on cardiac
      function. Despite its impact on morbidity and mortality, our understanding of the
      etiology and pathophysiology of this disease process is still incomplete. Over
      the past several decades, there has been evidence to suggest that AF has a
      significant correlation with metabolic syndrome (MetS). Furthermore, AF appears
      to be more closely related to specific components of MetS compared with others.
      This article provides an overview of the various components of MetS and their
      impact on AF. 

PMID- 24448258
TI  - Role of omega-3 fatty acids in the prevention of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting more
      than 2.6 million people in the United States. It occurs frequently after
      myocardial infarction and is the most common arrhythmia following cardiac
      surgery. AF increases the risk of morbidity and mortality from stroke,
      thromboembolism, and death. AF may be caused by ectopic activity in one or more
      of the pulmonary veins. Focal ectopic activity can be generated by abnormal
      atrial automaticity, delayed afterdepolarizations from calcium overload, or early
      afterdepolarizations secondary to defective repolarization properties. Pathologic
      mechanisms may include autonomic dysfunction, inflammation, and fibrosis. Omega-3
      fatty acids (polyunsaturated fatty acids [PUFAs]) have been shown to induce
      beneficial effects in the treatment of coronary artery disease. They may also
      reduce sudden cardiac death and the incidence of arrhythmias. Therefore, studies
      have been conducted to evaluate the benefits of PUFAs in arrhythmia prevention.
      This review describes the effects of PUFAs in AF and provides the current
      literature in the prevention of AF. 

PMID- 24448259
TI  - N-terminal prohormone B-type natriuretic peptide and cardiovascular risk in
      stable coronary artery disease: a meta-analysis of nine prospective studies.
AB  - To evaluate the prognostic value of N-terminal prohormone B-type natriuretic
      peptide (NT-proBNP) for patients with stable coronary artery disease, we searched
      for all published English-language articles indexed in MEDLINE and PubMed through
      July 2011. Nine independent, prospective, cohort studies that assessed the
      association between NT-proBNP value and long-term prognosis were identified. The
      interested endpoints of this meta-analysis were all-cause mortality and
      cardiovascular mortality and cardiovascular events. A general variance-based
      method was used to pool the hazard ratio (HR). In a comparison of individuals in
      the top quartile with those in the bottom quartile of baseline values of NT
      proBNP, the combined adjusted HR was 2.74 (95% confidence interval [CI], 1.85
      3.62). The combined HRs for the second and third quartiles compared with the
      first quartile were 1.33 (95% CI, 0.83-1.82) and 1.85 (95% CI, 1.23-2.48),
      respectively. In a subanalysis grouped by the median value, per 1 standard
      deviation increase or per 1000 pg/mL increase of NT-proBNP, the overall effect
      also showed that poor prognosis was significantly increased with the elevation of
      NT-proBNP (HR, 1.58; 95% CI, 1.16-2.01). Available prospective studies indicated
      strong associations between the circulating concentration of NT-proBNP and long
      term prognosis in patients with stable coronary artery disease. 

PMID- 24448260
TI  - An update on endovascular management of acute thoracic aortic disease and future
      directions.
AB  - Thoracic endovascular aortic repair (TEVAR) has become an alternative treatment
      option for acute thoracic aortic disease. This review focuses on current
      endovascular treatment of acute thoracic aortic disease and future directions of
      TEVAR. TEVAR is a promising alternative approach to open surgery, with lower
      early mortality and morbidity rates, especially in high-risk cohorts.
      Furthermore, with accumulating experience and improving device technology and
      imaging modalities, TEVAR has become safer and has potential to expand treatment
      options to include ascending and arch pathologies. 

PMID- 24448261
TI  - Isolation of a potassium bis(1,2,3-triazol-5-ylidene)carbazolide: a stabilizing
      pincer ligand for reactive late transition metal complexes.
AB  - The synthesis and X-ray crystal structure of a potassium adduct of a monoanionic
      CNC-pincer ligand featuring two mesoionic carbenes is reported. Owing to the
      peculiar electronic and steric properties of this ligand, the first neutral
      stable Ni(II)-hydride, and an unusual Cu(II) complex displaying a seesaw
      geometry, have been isolated.

PMID- 24448262
TI  - Cohort and age effects of mass drug administration on prevalence of trachoma: a
      longitudinal study in rural Tanzania.
AB  - PURPOSE: Mass drug administration (MDA) is part of the SAFE strategy for trachoma
      elimination. This study examined the effect of three annual MDAs on prevalence of
      trachoma among 13 longitudinal cohorts of Tanzanian children. METHODS: Children
      younger than 10 years were assigned to cohorts based on age at baseline and
      followed annually for 3 years, with newborns assigned to new cohorts over time.
      Annual MDA consisted of topical tetracycline for children younger than 6 months
      and oral azithromycin for those 6 months and older. Follicular trachoma (TF) and
      Chlamydia trachomatis infection status were assessed annually before the next
      MDA. Prevalence and risk factors for TF and infection at each age were compared
      across cohorts. RESULTS: At each survey, most age groups and cohorts had MDA
      coverage of more than 80% and showed decreased TF prevalence after every MDA. One
      cohort had consistently lower coverage, higher-than-expected TF and infection at
      ages 6 and 7, and elevated risk of TF at age 7 relative to the preceding cohort
      in spite of receiving one additional MDA (odds ratio 2.3, 95% confidence interval
      1.0-5.2). Cohorts aged 1 or older at baseline generally showed reductions in TF
      and infection after each MDA, whereas younger cohorts showed decreased infection
      but increased TF over time. Successive cohorts of never-treated children younger
      than 1 year showed sequential TF and infection reductions with each MDA (P <
      0.001). CONCLUSIONS: Multiple MDAs significantly reduce trachoma prevalence and
      appear to increasingly protect children born into these communities. The youngest
      children show declining/stable rates of infection but increasing rates of
      trachoma, which may reflect longer duration of clinical signs.

PMID- 24448263
TI  - Development and validation of an improved neurological hemifield test to identify
      chiasmal and postchiasmal lesions by automated perimetry.
AB  - PURPOSE: To improve the neurological hemifield test (NHT) using visual field data
      from both eyes to detect and classify visual field loss caused by chiasmal or
      postchiasmal lesions. METHODS: Visual field and clinical data for 633 patients
      were divided into a training set (474 cases) and a validation set (159 cases).
      Each set had equal numbers of neurological, glaucoma, or glaucoma suspect cases,
      matched for age and for mean deviation between neurological and glaucoma cases.
      NHT scores as previously described and a new NHT laterality score were
      calculated. The ability of these scores to distinguish neurological from other
      fields was assessed with receiver operating characteristic (ROC) analysis. Three
      machine classifier algorithms were also evaluated: decision tree, random forest,
      and least absolute shrinkage and selection operator (LASSO). We also evaluated
      the ability of NHT to identify the type of neurological field defect (homonymous
      or bitemporal). RESULTS: The area under the ROC curve (AUC) for the maximum NHT
      score was 0.92 (confidence interval [CI]: 0.87, 0.97). Using NHT laterality
      scores from each eye combined with the sum of NHT scores, the AUC improved to
      0.93 (CI: 0.88, 0.98). The largest AUC for machine learning algorithms was for
      the LASSO method (0.96, CI: 0.92, 0.99). The NHT scores identified the type of
      neurological defect in 96% (158/164) of patients. CONCLUSIONS: The new NHT
      distinguished neurological field defects from those of glaucoma and glaucoma
      suspects, providing accurate categorization of defect type. Its implementation
      may identify unsuspected neurological disease in clinical visual field testing.

PMID- 24448265
TI  - Amblyopic deficit beyond the fovea: delayed and variable single-trial ERP
      response latencies, but unaltered amplitudes.
AB  - PURPOSE: Amblyopia was first described as a deficit of central vision. However,
      it has long been debated whether this dysfunction is limited to the fovea or
      whether extrafoveal vision is also affected, as studies concerning the latter are
      equivocal. The purpose of the study was to resolve this issue. METHODS: We
      investigated the amblyopic effect on event-related potentials (ERPs) with foveal
      and perifoveal stimuli, either matched in size based on cortical magnification or
      presented as large annular stimuli. In two separate experiments we measured ERPs
      on amblyopic patients and control subjects using face images. Latency and
      amplitude of averaged ERPs and their single-trial distributions were analyzed.
      RESULTS: When the fovea was stimulated, latency and amplitude of the early
      averaged ERP components increased and were reduced, respectively, in the
      amblyopic compared with the fellow eye. Importantly, perifoveal stimulation also
      elicited similar amblyopic deficits, which were clearly significant in the case
      of using cortical magnification scaled stimuli. However, single-trial peak
      analysis revealed that foveal and perifoveal effects differed in nature: Peak
      amplitudes were reduced only in foveal stimulation, while latencies were delayed
      and jittered at both the fovea and perifovea. Event-related potentials obtained
      from fellow eyes were not significantly different from those of normal observers.
      CONCLUSIONS: Our findings revealed the existence of amblyopic deficits at the
      perifovea when the stimulated cortical area was matched in size to that of foveal
      stimulation. These deficits manifested themselves only in the temporal structure
      of the responses, unlike foveal deficits, which affected both component amplitude
      and latency.

PMID- 24448264
TI  - Outflow tract ablation using a conditionally cytotoxic feline immunodeficiency
      viral vector.
AB  - PURPOSE: To create an in vivo model of vector-mediated trabecular meshwork (TM)
      ablation and replacement. METHODS: We generated a conditionally cytotoxic,
      trackable vector, HSVtkiG, that expressed herpes simplex virus 1 thymidine kinase
      (HSVtk) and enhanced green fluorescent protein (eGFP). We optimized HSVtkiG
      ablation in vitro with ganciclovir (GCV) in comparison to eGFP control vector
      GINSIN and investigated the mechanism. Right eyes of 24 rats were then injected
      intracamerally with either HSVtkiG or GINSIN, before intraperitoneal GCV was
      administered 1 week later. Intraocular pressure, central corneal thickness (CCT),
      and slit-lamp exams were assessed for 8 weeks. Transduction and ablation were
      followed by gonioscopic visualization of eGFP. Histology was obtained with TM
      cell counts and immunohistochemistry markers of inflammation. RESULTS:
      Transduction and ablation parameters were established in vitro. Apoptosis was the
      cause of cell death. In vivo, transduction was seen gonioscopically to be
      targeted to the TM, followed by disappearance of eGFP marker fluorescence in
      HSVtkiG-transduced cells after injection of GCV. Ablation resulted in an IOP
      decrease of 25% in HSVtkiG-injected eyes 2 days after GCV but not in GINSIN or
      noninjected control eyes (P < 0.05). Trabecular meshwork cellularity was
      decreased at the time of lowest IOP and recovered thereafter, while CCT remained
      unchanged. Inflammation was absent. CONCLUSIONS: A vector-based system for
      inducible ablation of cells of the outflow tract was developed. Trabecular
      meshwork ablation lowered IOP, and recovery of cellularity and IOP followed. This
      model may be useful to study pressure regulation by the TM, its stem cells, and
      migration patterns.

PMID- 24448266
TI  - Mitochondrial DNA variant discovery in normal-tension glaucoma patients by next
      generation sequencing.
AB  - PURPOSE: Normal-tension glaucoma (NTG) is a disease of late onset, complex trait
      with multiple risk factors. In this study, we discovered a mitochondrial DNA
      variant in NTG patients using next-generation sequencing (NGS). METHODS: The DNA
      was extracted from the peripheral blood of NTG patients and normal control
      subjects. Sequencing of the entire mitochondrial DNA (mtDNA) using NGS revealed
      new genetic risk variants for NTG patients (discovery sample, n = 20). For the
      candidate genetic variants, we performed a disease-gene association study in the
      independent case-control populations (validation sample; NTG, n = 196 and normal
      control, n = 202) using Sanger sequencing. RESULTS: This study identified 148
      different novel mtDNA-sequence changes. Of these, 21 sequence variants identified
      at a frequency greater than 15% were located in the ND2-ND6, RNR1, RNR2, COX1,
      COX3, ATP6, ATP8, and CYTB genes. Of the 21 candidate genetic variants, the
      frequencies of m.4883C>T (ND2 gene), m.9540T>C (COX3 gene), and m.14766C>T (CYTB
      gene) were significantly different between NTG patients and controls (28.4% vs.
      15.3%, P = 0.002; 56.5% vs. 44.4%, P = 0.020; and 3.1% vs. 0.0%, P = 0.030,
      respectively). The association with m.4883C>T in the ND2 gene resisted the
      Bonferroni correction for multiple tests. The NTG patients of T genotype in the
      m.4883C>T variant have more advanced visual field loss than those who carry the C
      genotype (P = 0.009). CONCLUSIONS: This study reveals a spectrum of mtDNA
      variants in patients with NTG. Our results identified a synonymous change,
      m.4883C>T variant, which was more prevalent in the NTG cohorts than in the
      controls. This finding suggests that the identified variant may be a genetic risk
      factor for the development of NTG.

PMID- 24448267
TI  - Ocular pharmacokinetics of intravitreally administered brimonidine and
      dexamethasone in animal models with and without blood-retinal barrier breakdown.
AB  - PURPOSE: We compared ocular and systemic pharmacokinetics of brimonidine and
      dexamethasone following a single intravitreal dose in animals with blood-retinal
      barrier (BRB) breakdown and in healthy controls. METHODS: We induced BRB
      breakdown in rabbits by intravitreal injection of recombinant human VEGF165 and
      choroidal neovascularization (CNV) in monkeys with laser. Control and disease
      animals then received single intravitreal injections of brimonidine alone,
      dexamethasone alone, or brimonidine in combination with dexamethasone. Ocular
      tissues and plasma were collected and quantified for drug concentration using LC
      MS/MS assays. Statistical analysis was performed to compare the pharmacokinetic
      parameters between the control and disease animal models. RESULTS: In rabbits,
      brimonidine and dexamethasone exposure, as assessed by area under the drug
      concentration-time curve (AUC) in aqueous humor, retina, and choroid, was lower
      in disease than control animals, with a greater difference observed for
      dexamethasone than brimonidine. In monkeys, dexamethasone exposure was lower in
      disease than control animals for the central retina/choroid and peripheral
      choroid, whereas brimonidine exposure was lower in disease animals only in the
      central retina/choroid. Plasma exposure to both drugs was comparable between
      control and disease animals in both species. CONCLUSIONS: In animal models with a
      breakdown of the blood-retina barrier, drug clearance could be increased,
      resulting in lower drug concentration in ocular tissues compared to normal
      animals. However, the extent of difference may be compound- and disease model
      specific. Therefore, extrapolation of ocular pharmacokinetic data obtained in
      normal animals to disease models for the purpose of
      pharmacokinetic/pharmacodynamic data analysis should be performed with caution.

PMID- 24448268
TI  - Dietary fatty acids in health and disease: greater controversy, greater interest.

PMID- 24448269
TI  - Population structural analysis of O1 El Tor Vibrio cholerae isolated in China
      among the seventh cholera pandemic on the basis of multilocus sequence typing and
      virulence gene profiles.
AB  - Serogroup O1 Vibrio cholerae is the most common agents to cause epidemic and
      pandemic cholera disease. In this study, multilocus sequence typing (MLST) was
      performed on 160 serogroup O1 strains (including 42 toxigenic and 118 non
      toxigenic), and the virulence/fitness gene profiles of 16 loci were further
      analysed for 60 strains of these. Eighty-four sequence types (STs) with 14 clonal
      complexes were distinguished, and 29 STs were unique. Except SD19771005, all
      toxigenic strains were well-separated from the non-toxigenic strains. While a
      group of non-toxigenic strains clustered closer to the toxigenic strains compared
      to the other strains. Overall the examined gene loci showed higher presence rates
      in the toxigenic strains compared to the non-toxigenic strains. It is worth
      noting that the presence rates of VPI, TLC, VSP-I and VSP-II in the non-toxigenic
      strains that were clustered closer to the toxigenic strains were much higher
      compared to the other non-toxigenic strains. Our study indicated the complex
      population structure of O1 strains, and parts of non-toxigenic strains are
      genetically more closely related to toxigenic strains than other non-toxigenic
      strains, suggesting that these strains may have a higher potential for infection
      with CTXF in the environment or host intestine and is more efficient to become
      new pathogenic or epidemic clones. 

PMID- 24448270
TI  - Feasibility of sealed D-T neutron generator as neutron source for liver BNCT and
      its beam shaping assembly.
AB  - This paper involves the feasibility of boron neutron capture therapy (BNCT) for
      liver tumor with four sealed neutron generators as neutron source. Two generators
      are placed on each side of the liver. The high energy of these emitted neutrons
      should be reduced by designing a beam shaping assembly (BSA) to make them useable
      for BNCT. However, the neutron flux decreases as neutrons pass through different
      materials of BSA. Therefore, it is essential to find ways to increase the neutron
      flux. In this paper, the feasibility of using low enrichment uranium as a neutron
      multiplier is investigated to increase the number of neutrons emitted from D-T
      neutron generators. The neutron spectrum related to our system has a proper
      epithermal flux, and the fast and thermal neutron fluxes comply with the IAEA
      recommended values. 

PMID- 24448271
TI  - Diversity of human tRNA genes from the 1000-genomes project.
AB  - The sequence diversity of individual human genomes has been extensively analyzed
      for variations and phenotypic implications for mRNA, miRNA, and long non-coding
      RNA genes. TRNA (tRNA) also exhibits large sequence diversity in the human
      genome, but tRNA gene sequence variation and potential functional implications in
      individual human genomes have not been investigated. Here we capitalize on the
      sequencing data from the 1000-genomes project to examine the diversity of tRNA
      genes in the human population. Previous analysis of the reference human genome
      indicated an unexpected large number of diverse tRNA genes beyond the necessity
      of translation, suggesting that some tRNA transcripts may perform non-canonical
      functions. We found 24 new tRNA sequences in>1% and 76 new tRNA sequences in>0.2%
      of all individuals, indicating that tRNA genes are also subject to evolutionary
      changes in the human population. Unexpectedly, two abundant new tRNA genes
      contain base-pair mismatches in the anticodon stem. We experimentally determined
      that these two new tRNAs have altered structures in vitro; however, one new tRNA
      is not aminoacylated but extremely stable in HeLa cells, suggesting that this new
      tRNA can be used for non-canonical function. Our results show that at the scale
      of human population, tRNA genes are more diverse than conventionally understood,
      and some new tRNAs may perform non-canonical, extra-translational functions that
      may be linked to human health and disease. 

PMID- 24448272
TI  - Multi-valued logic gates based on ballistic transport in quantum point contacts.
AB  - Multi-valued logic gates, which can handle quaternary numbers as inputs, are
      developed by exploiting the ballistic transport properties of quantum point
      contacts in series. The principle of a logic gate that finds the minimum of two
      quaternary number inputs is demonstrated. The device is scalable to allow
      multiple inputs, which makes it possible to find the minimum of multiple inputs
      in a single gate operation. Also, the principle of a half-adder for quaternary
      number inputs is demonstrated. First, an adder that adds up two quaternary
      numbers and outputs the sum of inputs is demonstrated. Second, a device to
      express the sum of the adder into two quaternary digits [Carry (first digit) and
      Sum (second digit)] is demonstrated. All the logic gates presented in this paper
      can in principle be extended to allow decimal number inputs with high quality
      QPCs. 

PMID- 24448274
TI  - Meta-analysis of D-values of proteolytic Clostridium botulinum and its surrogate
      strain Clostridium sporogenes PA 3679.
AB  - Foodborne botulism is a serious disease resulting from ingestion of preformed
      Clostridium botulinum neurotoxin in foodstuff. Since the 19th century, the heat
      resistance of this spore forming bacteria has been extensively studied in order
      to guarantee the public health associated with low acidic, ambient stable
      products. The most largely used heat resistance parameters in thermal settings of
      such products are the D121.1 degrees C values (time required to have a 10-fold
      decrease of the spore count, at 121.1 degrees C) and the z-values (temperature
      increase to have a 10-fold decrease of D-values). To determine D121.1 degrees C
      and z-values of proteolytic C. botulinum and its nontoxigenic surrogate strain C.
      sporogenes PA3679, a dataset of 911 D-values was collected from 38 scientific
      studies. Within a meta-analysis framework, a mixed-effect linear model was
      developed with the log D-value (min) as response and the heat treatment
      temperature as explicative variable. The studies (38), the C. botulinum strains
      (11), and the heat treatment media (liquid media and various food matrices, split
      into nine categories in total) were considered as co-variables having a random
      effect. The species (C. botulinum and C. sporogenes) and the pH (five categories)
      were considered as co-variables having a fixed effect. Overall, the model gave
      satisfactory results with a residual standard deviation of 0.22. The heat
      resistance of proteolytic C. botulinum was found significantly lower than the C.
      sporogenes PA 3679 one: the mean D-values at the reference temperature of 121.1
      degrees C, in liquid media and pH neutral, were estimated to 0.19 and 1.28min for
      C. botulinum and C. sporogenes, respectively. On the other hand, the mean z
      values of the two species were similar: 11.3 and 11.1 degrees C for C. botulinum
      and C. sporogenes, respectively. These results will be applied to thermal
      settings of low-acid ambient stable products. 

PMID- 24448273
TI  - A source of antihydrogen for in-flight hyperfine spectroscopy.
AB  - Antihydrogen, a positron bound to an antiproton, is the simplest antiatom. Its
      counterpart-hydrogen--is one of the most precisely investigated and best
      understood systems in physics research. High-resolution comparisons of both
      systems provide sensitive tests of CPT symmetry, which is the most fundamental
      symmetry in the Standard Model of elementary particle physics. Any measured
      difference would point to CPT violation and thus to new physics. Here we report
      the development of an antihydrogen source using a cusp trap for in-flight
      spectroscopy. A total of 80 antihydrogen atoms are unambiguously detected 2.7 m
      downstream of the production region, where perturbing residual magnetic fields
      are small. This is a major step towards precision spectroscopy of the ground
      state hyperfine splitting of antihydrogen using Rabi-like beam spectroscopy.

PMID- 24448275
TI  - Prevalence and molecular characterization of sorbitol fermenting and non
      fermenting Escherichia coli O157:H7(+)/H7(-) isolated from cattle at
      slaughterhouse and slaughterhouse wastewater.
AB  - The prevalence and seasonal distribution of E. coli O157:H7(+)/H7(-) in an array
      of aged cattle at slaughter and its dissemination with slaughterhouse wastewater
      over a two year period in Turkey were investigated. For this purpose, a total of
      720 samples (240 rectoanal mucosal swap [RAMS], 240 carcass sponge and 240 bile
      samples) of 240 cattle categorized according to age, gender, breed and sampling
      site were collected along with additional 24 wastewater samples and were
      subjected to immunomagnetic separation based cultivation technique to efficiently
      isolate E. coli O157 from the background flora. Identification (rfbEO157,
      fliCh7), detection of major virulence factors (stx1, stx2, eaeA, hly, lpfA1-3 and
      espA), intimin variants (eae-alpha1, eae-alpha2, eae-beta, eae-beta1, eae-beta2,
      eae-gamma1 and eae-gamma2/theta) and shiga toxin variants (stx1c, stx1d, stx2c,
      stx2d, stx2e, stx2f and stx2g) of all the isolates were assessed by PCR. From 10
      (4.2%) of RAMS and 11 (4.6%) of carcass sponge samples and 5 (20.8%) of
      slaughterhouse wastewater samples, a total of 102 colonies (99 sorbitol negative
      and 3 sorbitol positive) were isolated. Overall, 17 (7.1%) and 15 (6.3%) of 240
      sampled cattle were shown to harbor E. coli O157 and E. coli O157:H7,
      respectively either in their RAMS or carcass sponge samples analyzed.
      Statistically significant differences between categories; season, age, gender and
      breed of cattle were not observed (p>0.05). None of the isolated E. coli
      O157:H7(+)/H7(-) strains harbored any of the investigated intimin types other
      than eaegamma1 or shiga toxin variants stx1d, stx2e, stx2f or stx2g while all
      were lpfA1-3(+) except 5 E. coli O157:H7(-) strains. Intimin variant eaegamma1
      and shiga toxin 1 variant stx1c were detected from all of the eaeA(+) (97/102,
      95.1%) and stx1(+) (32/102, 31.3%) strains, respectively while from stx2(+)
      (80/102, 78.4%) isolates, both stx2c (68/80, 85.0%) and stx2d (12/80, 15.0%)
      variants were determined. In the last decade, prevalence of E. coli O157:H7 has
      an increasing trend in cattle. Slaughterhouses are the significant sources of
      environmental contamination with E. coli O157:H7. Isolation and molecular
      characterization of sorbitol fermenting E. coli O157:H7 are a novel finding and
      may lead to a revision of reference isolation procedure of E. coli O157:H7 in
      future. 

PMID- 24448276
TI  - Antimicrobial beeswax coated polylactide films with silver control release
      capacity.
AB  - Although the application of silver based antimicrobial systems is a widespread
      technology, its implementation in areas such as food packaging is still
      challenging. The present paper describes the fabrication of poly(lactic acid)
      (PLA) coated with beeswax with controlled release properties for sustained
      antimicrobial performance. Release of silver ions from the polymers was monitored
      voltammetrically under various conditions (surface contact, immersion in various
      liquid media and at different pH values) throughout at least 7days. A higher
      release was noted with decreasing pH while surface release was much slower than
      the release when immersed in liquid medium. While uncoated films demonstrated a
      high burst release which in some instances implied surpassing some current
      migration restrictions (<0.05mg/kg food), the addition of a beeswax layer allowed
      a sustained release of the antimicrobial compound. Increasing the thickness of
      the beeswax layer resulted in an increase in the water barrier properties of the
      films while reducing the relatively constant values of sustained release.
      Antimicrobial performance was correlated with the release of silver ions,
      indicating threshold concentrations for biocide action of <6MUg/L and 9-14MUg/L
      for surface contact and in liquid media, respectively. Either by surface contact
      or by immersion in growth medium or vegetable soup, the coated films displayed a
      strong bactericidal effect against Salmonella enterica. The application of this
      functional barrier thus offers the possibility of tuning the release profiles of
      the films to suit a specific application and puts forth the possible suitability
      of these materials for food packaging or other migration sensitive applications. 

PMID- 24448277
TI  - A multi-agent-based, semantic-driven system for decision support in epidemic
      management.
AB  - Issues in epidemiology are truly multidisciplinary, requiring knowledge from
      diverse disciplines such as sociology, medicine, biology, geography and
      information science. Such inherent complexity has led to a challenge in
      developing decision support systems for epidemic information management,
      especially when data are from heterogeneous origins. In order to achieve a
      solution, an integrative framework is proposed. The Semantic Web is introduced in
      the context of enriching meaningful and machine-readable descriptions of
      epidemiological data. Software agents are utilised to achieve automation in
      semantic discovery, composition of data and process services. The objective is to
      enhance the performance in information retrieval in a dynamic decision-making
      environment while concealing technical complexity from inexperienced users. We
      illustrate how a prototype system can be developed by considering an epidemiology
      management scenario in which spatio-temporal analysis is undertaken of a
      specified epidemic. 

PMID- 24448278
TI  - Tuberculosis-Diagnostic Expert System: an architecture for translating patients
      information from the web for use in tuberculosis diagnosis.
AB  - BACKGROUND: Over 1.5-2 million tuberculosis deaths occur annually. Medical
      professionals are faced with a lot of challenges in delivering good health-care
      with unassisted automation in hospitals where there are several patients who need
      the doctor's attention. OBJECTIVE: To automate the pre-laboratory screening
      process against tuberculosis infection to aid diagnosis and make it fast and
      accessible to the public via the Internet. The expert system we have built is
      designed to also take care of people who do not have access to medical experts,
      but would want to check their medical status. METHODS: A rule-based approach has
      been used, and unified modeling language and the client-server architecture
      technique were applied to model the system and to develop it as a web-based
      expert system for tuberculosis diagnosis. Algorithmic rules in the Tuberculosis
      Diagnosis Expert System necessitate decision coverage where tuberculosis is
      either suspected or not suspected. The architecture consists of a rule base,
      knowledge base, and patient database. These units interact with the inference
      engine, which receives patient' data through the Internet via a user interface.
      RESULTS: We present the architecture of the Tuberculosis-Diagnosis Expert System
      and its implementation. We evaluated it for usability to determine the level of
      effectiveness, efficiency and user satisfaction. The result of the usability
      evaluation reveals that the system has a usability of 4.08 out of a scale of 5.
      This is an indication of a more-than-average system performance. CONCLUSION:
      Several existing expert systems have been developed for the purpose of supporting
      different medical diagnoses, but none is designed to translate tuberculosis
      patients' symptomatic data for online pre-laboratory screening. Our Tuberculosis
      Diagnosis Expert System is an effective solution for the implementation of the
      needed web-based expert system diagnosis.

PMID- 24448279
TI  - Preliminary functional results and quality of life after implantation of a new
      bone conduction hearing device in patients with conductive and mixed hearing
      loss.
AB  - OBJECTIVE: To review functional results and quality of life of the first patients
      implanted with a newly introduced bone conduction implant system. STUDY DESIGN:
      Retrospective chart analysis of 6 patients (6 ears) implanted for conductive
      hearing loss (CHL) and mixed hearing loss (MHL) in 1 tertiary referral center
      between July 2012 and February 2013. METHODS: Implantation of a new bone
      conduction hearing device. Pure tone audiometry (air conduction and bone
      conduction thresholds, pure tone average, air-bone gap, and functional gain),
      speech audiometry (Freiburg Monosyllabic Test), intraoperative and postoperative
      complication rate, and patient satisfaction (Glasgow benefit inventory [GBI])
      were assessed. RESULTS: Air-conduction pure tone average (PTA) was 58.8 +/- 8.2
      dB HL. Unaided average air-bone gap (ABG) was 33.3 +/- 6.2 dB. Aided air
      conduction PTA in sound field was 25.2 +/- 5.1 dB HL. Aided average ABG was -0.3
      +/- 7.3 dB. Average functional gain was 33.6 +/- 7.2 dB. Mean improvement of GBI
      was +36.1. No intraoperative complications occurred. During a follow-up period of
      8.5 +/- 2.2 months, no device failure and no need for revision surgery occurred.
      CONCLUSION: Audiometric results of the new bone conduction hearing system are
      satisfying and comparable to the results of devices that have been applied
      previously for CHL and MHL. Intraoperatively and postoperatively, no
      complications were noted.

PMID- 24448280
TI  - A new bone conduction implant: surgical technique and results.
AB  - OBJECTIVE: To describe the surgical technique under local or general anesthesia
      of 5 cases that have undergone this procedure and the audiologic results obtained
      with this new device. PATIENTS: Four patients with mixed hearing loss and 1
      patient with single-sided deafness. INTERVENTION: Therapeutic. MAIN OUTCOME
      MEASURES: The surgery was planned beforehand with a 3D reconstruction of a CT
      scan. The procedure was documented and timed in every case. Air and bone
      conductive pure tone audiometry and disyllabic words discrimination were tested
      after and before the procedure. Results were statistically analyzed. RESULTS: All
      patients tolerated well the procedure. Four patients were intervened under local
      anesthesia and 1 under general anesthesia because of an associated procedure. All
      patients showed statistically significant difference between the presurgery and
      postsurgery audiologic tests. CONCLUSION: Implantation of the Bonebridge with
      local or general anesthesia is a safe and feasible procedure, with audiometric
      results that can come close with the ones provided by BAHD users.

PMID- 24448281
TI  - Amplification options for patients with mixed hearing loss.
AB  - OBJECTIVES: To compare amplification options for patients with mixed hearing
      loss. Devices tested include percutaneous and transcutaneous bone conductors
      (BCDs) and middle ear implants with their actuator directly coupled to the
      cochlea. SETTING: Tertiary academic medical center. METHOD AND PARTICIPANTS:
      Maximum output was studied with simulators. As simulators are lacking for the
      middle ear implants (the Vibrant Soundbridge [VSB] and the Cochlear's Direct
      Acoustic Cochlear Stimulator [Codacs]), the maximum output had to be measured in
      patients (4 and 5 patients, respectively). MAIN OUTCOME MEASURE: The maximum
      output averaged at 0.5, 1, and 2 kHz was the main outcome measure, which was
      expressed in dB HL, using appropriate transformation tables. RESULTS: The maximum
      output was the highest for the Codacs device and was above the patients'
      uncomfortable loudness levels. The maximum output of the VSB varied between 65
      and 85 dB HL, and that of percutaneous BCD varied between 68 and 80 dB HL
      depending on the type of device. The transcutaneous BCD, the Sophono device, had
      the lowest output. CONCLUSION: Only with the Codacs device can the complete
      dynamic range be used. The maximum output of the VSB is lower and variable owing
      to the coupling to the cochlea. For patients with a sensorineural hearing loss
      component up to 50 dB HL, a percutaneous BCD forms a good treatment option that
      is completely independent of the middle ear status. The transcutaneous Sophono
      BCD is suitable for patients with a (sub-)normal sensorineural hearing loss
      component of 20 dB or less.

PMID- 24448282
TI  - Change in endocochlear potential during experimental insertion of a simulated
      cochlear implant electrode in the guinea pig.
AB  - OBJECTIVE: Preservation of residual hearing during cochlear implantation is
      important. This study investigated changes in endocochlear potential (EP) during
      simulated cochlear implant (CI) electrode insertion. STUDY DESIGN: Laboratory
      animal study. SETTING: Academic hospital laboratory. SUBJECTS AND METHODS: Guinea
      pigs were divided into 4 groups: cochleostomy only (4 animals), suction after
      cochleostomy (5 animals), simulated CI electrode insertion parallel to the
      longitudinal axis of the scala tympani without suctioning (7 animals), and
      simulated CI electrode insertion toward the modiolus without suctioning (7
      animals). The EP was measured from the second turn of the cochlea, and the values
      after 20 minutes were compared. RESULTS: The EP showed little change at 20
      minutes after cochleostomy with a nearly normal value of 84.83 +/- 2.12 mV.
      Suctioning of the perilymph from the cochleostomy site caused a slight acute
      reduction in EP by about 6 mV, and the value at 20 minutes after cochleostomy was
      78.64 +/- 4.42 mV. Insertion of the simulated CI electrode parallel to the
      longitudinal axis of the scala tympani caused a slight decrease in EP to 78.91 +/
      5.06 mV. Insertion toward the modiolus caused a marked decrease in EP to 54.13
      +/- 4.42 mV at 20 minutes after the treatment, significantly lower compared with
      the other 3 groups. CONCLUSION: EP was well preserved during carefully performed
      surgical procedures of simulated CI electrode insertion, but it decreased
      significantly if the simulated CI electrode was inserted toward the modiolus.
      Careful attention is necessary to ensure the correct direction of CI electrode
      insertion to preserve residual hearing. Use of suction should be minimized if
      possible.

PMID- 24448283
TI  - Adult progressive sensorineural hearing loss: is preoperative imaging necessary
      before cochlear implantation?
AB  - OBJECTIVE: Preoperative evaluation of cochlear implant candidate includes routine
      imaging to identify anatomic abnormalities that may preclude or complicate
      implantation, such as cochlear aplasia, absent/narrowed internal auditory canals,
      cochlear ossificans, or significant traumatic fracture. The aim of this study is
      to determine if preoperative imaging is necessary in select cochlear implant
      candidates, thus defraying cost and ionizing radiation. STUDY DESIGN:
      Retrospective chart review. SETTING: Tertiary referral facility. PATIENTS: Adult
      patients with progressive sensorineural hearing loss without evidence of head
      trauma, meningitis, or congenital hearing loss who underwent cochlear
      implantation. INTERVENTIONS: Diagnostic and therapeutic. MAIN OUTCOME MEASURES:
      Preoperative radiologic abnormalities, deviation from standard cochlear implant
      operation. RESULTS: One hundred eighteen cochlear implants met inclusion
      criteria; 23.7% of CT scans had a documented abnormality, including chronic
      otitis media (14.4%), otosclerosis (4.2%), and an enlarged vestibular aqueduct
      (3.4%). There were 6 eventful surgeries in patients with normal documented CT
      scan. Events included multiple insertion attempts (3.4%), CSF leak (2.5%), and no
      apparent round window (2.5%). In every case, a cochlear implant was able to be
      placed successfully. CONCLUSION: In the appropriately selected patient,
      preoperative imaging is not necessary as it does not impact the cochlear implant
      surgery and will defray cost and ionizing radiation.

PMID- 24448284
TI  - Documenting immunization of children in a cochlear implant program.
AB  - PURPOSE: Assess the effectiveness of an immunization verification protocol (IVP)
      to achieve and document pneumococcal vaccination of patients with cochlear
      implants. STUDY DESIGN: Chart review. SETTING: Academic tertiary medical center.
      PATIENTS: Pediatric patients with cochlear implants (n = 76). OUTCOME MEASURES:
      1) Status of pneumococcal immunization for cochlear implant patients, before and
      after initiation of the IVP; 2) final number of existing cochlear implant
      patients successfully immunized after institution of the IVP; and 3)
      effectiveness of communication between our office and patient/parent or
      pediatrician. RESULTS: Subjects were grouped according to whether their cochlear
      implantation was performed before (Group 1, n = 63) or after (Group 2, n = 18)
      initiation of the IVP in September 2010. In the 28 months between IVP initiation
      and January 2013, the number of fully immunized age-eligible patients increased
      in Group 1 from 2% (n = 1) to 63% (n = 40). Of 18 subjects in Group 2, 56% (n =
      10) were fully vaccinated at the time of surgery, and 94% were fully vaccinated
      at the conclusion of the study (n = 17). Of all 81 children, complete
      immunization was documented in 70% (n = 57), incomplete documentation was noted
      in 16% (n = 13); and 14% (n = 11) were lost to follow-up. CONCLUSION: It is a
      challenge to achieve and document immunizations recommended for cochlear
      implantation, even in a relatively small cochlear implant program. In our
      practice, those patients who were required to document immunizations before
      surgery had the highest rates of compliance. Access to a vaccination registry and
      the ability to administer vaccines in the otolaryngology office also improved
      compliance.

PMID- 24448285
TI  - Cochlear implantation in late-implanted prelingually deafened adults: changes in
      quality of life.
AB  - BACKGROUND: With expanding inclusion criteria for cochlear implantation, the
      number of prelingually deafened persons who are implanted as adults increases.
      Compared with postlingually deafened adults, this group shows limited improvement
      in speech recognition. In this study, the changes in health-related quality of
      life in late-implanted prelingually deafened adults are evaluated and related to
      speech recognition. METHODS: Quality of life was measured before implantation and
      1 year after implantation in a group of 28 prelingually deafened adults, who had
      residual hearing and who used primarily oral communication. Patients completed 3
      questionnaires (Nijmegen Cochlear Implant Questionnaire, Glasgow Benefit
      Inventory, and Health Utility Index 3). Postoperative scores were compared with
      preoperative scores. Additionally, phoneme recognition scores were obtained
      preimplantation and 1 year postimplantation. RESULTS: Quality of life improved
      after implantation: scores on the Nijmegen Cochlear Implant Questionnaire
      improved significantly in all subdomains (basic speech perception, advanced
      speech perception, speech production, self-esteem, activity, and social
      interaction), the total Glasgow Benefit Inventory score improved significantly,
      and the Health Utility Index 3 showed a significant improvement in the utility
      score and in the subdomains "hearing" and "emotion." Additionally, a significant
      improvement in speech recognition scores was found. No significant correlations
      were found between gain in quality of life and speech perception scores.
      CONCLUSION: The results suggest that quality of life and speech recognition in
      prelingually deafened adults significantly improved as a result of cochlear
      implantation. Lack of correlation between quality of life and speech recognition
      suggests that in evaluating performance after implantation in prelingually
      deafened adults, measures of both speech recognition and quality of life should
      be used.

PMID- 24448286
TI  - Cochlear implantation versus auditory brainstem implantation in bilateral total
      deafness after head trauma: personal experience and review of the literature.
AB  - OBJECTIVE: To determine the effectiveness of cochlear implant (CI) in hearing
      restoration after temporal bone (TB) fractures and investigate the adequacy of
      auditory brainstem implant (ABI) indication for TB fractures. STUDY DESIGN:
      Retrospective clinical study; a systematic review of the literature in PubMed was
      also performed to identify all published cases of bilateral TB fractures or
      bilateral deafness after head trauma treated by means of CI or ABI. SETTINGS:
      Quaternary otology and skull base surgery referral center. PATIENTS: Eleven
      consecutive patients presented with bilateral severe-to-profound sensorineural
      hearing loss after head trauma. INTERVENTIONS: CI as primary intervention or
      following a previous treatment. MAIN OUTCOME MEASURES: CI performances were
      evaluated in the auditory-only condition in both closed-set and open-set formats.
      RESULTS: Fourteen CI were placed, 11 as primary treatment and 3 after ABI
      failure. At the last follow-up, all patients gained useful open-set speech
      perception. In secondary CI, all patients obtained better auditory results with
      the CI if compared with ABI. CI performance did not decrease with time in any
      case. CONCLUSION: Cochlear implantation after TB fractures has proved to have
      excellent audiometric results. The aim of the initial evaluation of a patient
      with bilateral anacoustic ears from head trauma should always be to rehabilitate
      their hearing with a CI. The incidence of labyrinthitis ossificans, negative
      electrophysiologic testing, the risk of postoperative meningitis or facial nerve
      stimulation should not be the determinant factors that favor ABI placement.

PMID- 24448287
TI  - Improving sound localization after cochlear implantation and auditory training
      for the management of single-sided deafness.
AB  - OBJECTIVE: To report a successful case of cochlear implantation and auditory
      training for the improvement of sound localization in a patient with single-sided
      deafness. STUDY DESIGN: Case report and literature review. SETTING: Tertiary
      referral otology practice. PATIENT: Fifty-seven-year-old man receiving cochlear
      implantation after 8 years of unilateral sensorineural hearing loss.
      INTERVENTION: Initially, CROS hearing aid, then osseointegrated bone conduction
      system and finally cochlear implantation and auditory training. MAIN OUTCOME
      MEASURES: Sound localization tests. RESULT: Sound localization tests after CI and
      auditory training showed improvement when compared with testing performed after
      fitting of an osseointegrated bone conduction system. CONCLUSION: Cochlear
      implantation followed by 3 months of auditory training may have improved sound
      localization in this patient with single-sided deafness. Further case-controlled
      studies need to be undertaken to ascertain whether CI alone without formal
      auditory training will promote the same results.

PMID- 24448288
TI  - Safety and functional results of early cochlear implant switch-on in children.
AB  - OBJECTIVE: To assess the safety and the possible advantages of early (1-wk)
      cochlear implant switch-on in children and to compare impedance and ECAP
      threshold changes between subjects undergoing early switch-on and those
      undergoing traditional, 1-month switch-on. STUDY DESIGN: Prospective cohort
      study. SETTING: Tertiary care referral pediatric center. PATIENTS: Seventeen
      children receiving a unilateral or bilateral Nucleus Freedom cochlear implant
      were included, for a total of 20 ears. Ten ears were assigned to the early (1-wk)
      switch-on group and 10 to the control group (switch-on after 4 wks).
      INTERVENTIONS: Common ground impedance values and electrically evoked compound
      action potential thresholds were measured from intraoperation until 9 months
      postoperatively. Speech perception improvements over time were also assessed.
      MAIN OUTCOME MEASURES: Complication rate, impedance levels (kOmega), and
      electrically evoked compound action potentials (current levels) RESULTS: Early
      switch-on was well tolerated by patients and did not cause complications.
      Impedances dropped significantly after switch-on in both groups. They also seemed
      to achieve an earlier stability in the early switch-on patients, although the
      difference between groups was not significant. ECAP thresholds showed a similar,
      nonsignificant decreasing trend over time in both groups. Speech perception
      improvements did not differ between groups. CONCLUSION: This is the first study
      investigating the safety and the effects of an early cochlear implant switch-on
      in children. Results show that such a procedure is well tolerated by pediatric
      subjects and free from complications. Impedance measurements suggest that the
      earlier switched-on subjects benefit of lower and more stable impedances than
      subjects undergoing 1-month switch-on.

PMID- 24448289
TI  - Vestibular dysfunction in Turner syndrome: a case report.
AB  - OBJECTIVE: Turner syndrome is a well-known cause of sensorineural hearing loss,
      and the lack of estrogen has been implicated in cochlear dysfunction. It has
      never been associated with vestibular dysfunction. We report a case of a patient
      with Turner syndrome who was found to have bilateral vestibular dysfunction based
      on video-oculography (VOG) testing. PATIENT: A single patient with a history of
      Turner syndrome who was found to have significant bilateral vestibular
      dysfunction. INTERVENTION: After noticing a deficit in the vestibulo-ocular
      reflexes on qualitative horizontal head impulse examination, the patient
      underwent VOG testing. MAIN OUTCOME MEASURE: VOG testing quantatively measures
      angular vestibulo-ocular reflex (AVOR) gain in the horizontal semicircular canal
      plane. AVOR gain represents the eye movement response to a head movement; in
      normal individuals the eye movement is fully compensatory and gain values are
      close to unity. RESULTS: VOG results showed AVOR gains of 0.29 and 0.36 on the
      right and left sides, respectively. CONCLUSION: We have presented a case of a
      woman with Turner syndrome with asymptomatic vestibular dysfunction demonstrated
      with VOG testing. Although there is a documented relationship between Turner
      syndrome and sensorineural hearing loss, there are no previous studies or case
      reports linking Turner syndrome and vestibular dysfunction. Additional research
      and added vigilance in monitoring Turner syndrome patients may be warranted.

PMID- 24448290
TI  - Perilymph fistula presenting with contralateral symptoms.
AB  - OUTCOME OBJECTIVES: To report the case of a contralateral Tullio phenomenon,
      suggest possible pathophysiology, and give insight into normal vestibular
      physiology. PATIENTS: Twenty-year-old female subject who presented with 8-month
      symptoms of left-sided Tullio phenomenon after a motor vehicle collision. Testing
      suggested a right perilymphatic fistula. INTERVENTION(S): Bedrest and a right
      perilymphatic fistula repair. MAIN OUTCOME MEASURE(S): Cervical vestibular evoked
      myogenic potentials (cVEMPs), audiometry, and patient symptoms. RESULTS:
      Postoperatively, the patient's symptoms of left-sided Tullio phenomenon abruptly
      abated, and the patient reported no activity limitations. Vertigo and phonodynia
      could not be reproduced. Postoperative VEMP demonstrated marked normalization
      (from abnormally decreased right-sided threshold and increased amplitude
      preoperatively). The left continued to demonstrate no abnormalities on audiogram,
      tympanogram, or VEMP. CONCLUSION: This is the first known report of symptoms
      presenting contralateral to the side of perilymph fistula and represents a window
      of understanding to vestibular physiology. The cause of this unique finding may
      rest in the failure of commissural inhibition after labyrinth dysfunction.
      Clinicians should maintain heightened awareness for the possibility of inner ear
      dysfunction contralateral to symptoms.

PMID- 24448291
TI  - Middle ear gentamicin-soaked pledgets in the treatment of Meniere's disease.
AB  - OBJECTIVE: Assess the relative efficacy and results of the round window
      hyaluronic acid pledget depot method for intratympanic gentamicin delivery in
      Meniere's disease. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
      referral hospital. PATIENTS: Prospective symptomatic and audiologic data were
      collected on 28 patients undergoing intratympanic gentamicin therapy for
      Meniere's disease refractory to medical treatment between 2003 and 2009.
      INTERVENTION: All patients had the round window membrane exposed via a
      tympanomeatal flap, and any adhesions were removed. Hyaluronic acid pledgets
      soaked in 40 mg/ml of gentamicin were then packed into the round window niche and
      posterior mesotympanum, and the tympanomeatal flap was replaced. MAIN OUTCOME
      MEASURES: Patients audiologic and vertigo symptom outcome scores were recorded at
      follow-up according to the AAO-HNS 1995 guidelines for reporting results in
      Meniere's disease. RESULTS: Complete or substantial improvement in vertigo (class
      A or B) was achieved in 88.5% (23/26) of patients. Hearing loss, defined as
      greater than 10 dB (PTA average at 0.5, 1, 2, and 4 kHz) was noted in 12 (50%) of
      24 patients including 4 patients who had developed "dead ears" (16%). The average
      hearing loss for all patients excluding the 4 patients with dead ears was 10.7
      dB. CONCLUSION: Round window hyaluronic acid pledget technique used as a
      sustained delivery vehicle for intratympanic gentamicin treatment for Meniere's
      disease produces similar rates of vertigo control compared with other techniques
      but a greater risk of hearing loss. We would recommend the intratympanicinjection
      titration technique as first line for most patients.

PMID- 24448292
TI  - Benign paroxysmal positional vertigo--toward new definitions.
AB  - OBJECTIVE: To review new clinical data and theories concerning atypical
      positional nystagmus in vertical canal benign paroxysmal positional vertigo
      (BPPV). DATA SOURCES: Peer reviewed, clinical papers describing nystagmus
      provoked by positioning in cases with BPPV. STUDY SELECTION: Basic scientific
      articles detailing 3D anatomical reconstructions of the inner ear. CONCLUSION: In
      BPPV, it is hypothetically possible that otoconia become dislocated but do not
      fall into the common crus of the vertical canals or into the horizontal canal; in
      these cases, they may gravitate toward the most inferior part of the utriculus,
      the ampulla of the inferior canal. It is argued that in these cases, depending on
      their behavior (free-floating or sticking to the cupula) and the precise position
      of the inferior ampulla, either no nystagmus or a slow downbeat nystagmus should
      ensue when the patient is positioned from sitting to a Dix-Hallpike position.
      Such scenarios could hypothetically explain commonly seen clinical entities such
      as "subjective BPPV" and/or cases with a peripheral positional downbeat
      nystagmus.

PMID- 24448293
TI  - A novel method of 3D image analysis of high-resolution cone beam CT and multi
      slice CT for the detection of semicircular canal dehiscence.
AB  - HYPOTHESIS: We investigated if current-generation computed tomographic (CT)
      scanners have the resolution required to objectively detect bone structure
      defects as small as 0.1 mm. In addition, we propose that our method is able to
      predict a possible dehiscence in a semicircular canal. BACKGROUND: In
      semicircular canal dehiscence (SCD), the bone overlying the superior canal (SC)
      is partially absent, causing vertigo, autophony, hyperacusis or hearing loss.
      Diagnosis of SCD is typically based on multi-slice computed tomography (MSCT)
      images combined with the consideration of clinical signs and symptoms. Recent
      studies have shown that MSCT tends to overestimate the size of dehiscences and
      may skew the diagnosis towards dehiscence when a thin bone layer remains.
      Evaluations of CT scans for clinical application are typically observer based.
      METHODS: We developed a method of objectively evaluating the resolution of CT
      scanners. We did this for 2 types of computed tomography: MSCT, and cone beam
      computed tomography (CBCT), which have been reported to have a higher resolution
      for temporal bone scans. For the evaluation and comparison of image accuracy
      between different CT scanners and protocols, we built a bone cement phantom
      containing small, well-defined structural defects (diameter, 0.1-0.4 mm). These
      small inhomogeneities could reliably be detected by comparing the variances of
      radiodensities of a region of interest (i.e., a region containing a hole) with a
      homogenous region. The Fligner-Killeen test was used to predict the presence or
      absence of a hole (p >= 0.05). For our second goal, that is, to see how this
      technique could be applied to the detection of a possible dehiscence in a SC, a
      cadaveric head specimen was used to create an anatomic model for a borderline
      SCD; the SC was drilled to the point of translucency. After semi-automatically
      fitting the location of the canal, our variance-based approach allowed a clear,
      significant detection of the thin remaining bone layer. RESULTS: Our approach of
      statistical noise analysis on bone cement phantoms allowed us to distinguish real
      irregularities from measured image noise or reconstruction errors. We have shown
      that with computed tomography, an approach comparing radiodensity variance in
      regions of interest is capable of detecting inhomogeneities down to 0.1 mm (p <=
      0.0001). CONCLUSION: Our analysis of data from the cadaveric head specimen
      demonstrates that this approach can be used to objectively detect thin layers of
      bone overlying an SC. This should provide the basis for using this approach for a
      semi-automated, objective detection of SCD.

PMID- 24448294
TI  - Superior canal dehiscence: can we predict the diagnosis?
AB  - OBJECTIVE: Identify independent clinical and audiometric factors to predict a
      positive high-resolution computed tomography (HRCT) scan for superior canal
      dehiscence (SCD). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary
      referral center. PATIENTS: Patients presenting SCD. INTERVENTION(S): Audiogram,
      VEMP, temporal bone HRCT, and SCD symptoms and signs chart. MAIN OUTCOME
      MEASURE(S): ABG, VEMP threshold, and symptoms and signs. RESULTS: Approximately
      106 patients with SCD symptoms were included: 62 had a positive and 44 had a
      negative CT scan. The positive scan group showed a higher average of cochlear
      symptoms than the negative CT scan group (4.3 versus 2.6) (p < 0.001), but no
      statistical difference for vestibular symptoms (2.2 versus 1.8) was identified.
      CVEMP thresholds of the positive and negative CT scan groups were of 66 and 81
      dB, respectively (p < 0.001). The positive CT scan group showed higher ABGs at
      250 Hz (24 versus 14 dB) and 500 Hz (17 versus 8 dB) (p = 0.008 and p = 0.008,
      resectively). No statistical significance was found when comparing both groups
      for air and bone conduction thresholds. Approximately 23% of the positive CT scan
      group showed a Valsalva-induced vertigo against 2.3% of the negative scan group
      (p = 0.003); 27% of the positive CT scan group showed speculum-induced vertigo
      but none of the negative scan patients (p < 0.001). Using logistic regression, we
      found that each 10-dB unit increase in the 250 Hz ABG is associated to an
      increase odd of having SCD of 51% (OR, 1.51; 95% CI, 1.10-2.08). CONCLUSION:
      Nature and number of cochlear symptoms, Valsalva and pneumatic speculum-induced
      vertigo, VEMP thresholds, and ABGs seem to correlate with a positive HRCT. The
      ABG at 250 Hz is the most accurate predictor of SCD.

PMID- 24448295
TI  - ICP, BMI, surgical repair, and CSF diversion in patients presenting with
      spontaneous CSF otorrhea.
AB  - OBJECTIVE: To assess intracranial pressure (ICP), body mass index (BMI), surgical
      repair, and cerebrospinal fluid (CSF) diversion in patients presenting with
      spontaneous CSF otorrhea. STUDY DESIGN: Retrospective series review. SETTING:
      Tertiary referral center. PATIENTS: Thirty-two patients were treated surgically
      from 2004 to 2013 for spontaneous CSF otorrhea by the principal investigators.
      Patients with a history of chronic ear disease and cholesteatoma, previous
      mastoid surgery, head trauma, or iatrogenic injury were excluded. Average age was
      56 years. Twenty-two patients (69%) were female. INTERVENTION(S): Middle fossa
      repair, transmastoid repair, lumbar puncture, V-P shunt, L-P shunt, and magnetic
      resonance imaging. MAIN OUTCOME MEASURE(S): Patients underwent middle fossa or
      transmastoid repair of tegmen defects. Intracranial pressures were determined
      with lumbar puncture at time of surgical repair or shortly after surgery. CSF
      diversion procedures were performed in patients who were found to have elevated
      ICP, which was not controlled medically, presented with recurrent leak or had ICP
      of 25 cm or greater of H2O. Preoperative BMI was calculated. RESULTS: Thirty-two
      patients underwent 37 operations. Average BMI was 35.0 kg/m2 (median, 34.7;
      range, 18.7-53.2 kg/m2). There were 21 repairs on the left and 16 on the right.
      The majority underwent a middle fossa craniotomy for repair (27/32). Two patients
      had bilateral repairs. Three patients (8%) underwent revision surgery, of which,
      2 had untreated intracranial hypertension (ICP 24.5 and 24 cm H2O). ICP
      measurements were available for 29 patients. The mean ICP was 23.4 cm H2O
      (median, 24; range, 13-36 cm H20). Twenty-two patients (69%) had ICP of 20 cm or
      greater of H20; of those, 13 had an ICP of 25 cm or greater of H20. Seventeen
      patients (53%) underwent CSF diversion procedures. CONCLUSION: Our findings of
      elevated ICP and BMI in patients presenting with spontaneous CSF otorrhea are
      consistent with previous reports in the literature. The percentage of patients
      that underwent CSF diversion procedures was high at 53% and represents an
      aggressive stance in managing elevated ICP in a population that may be at risk
      for subsequent leaks.

PMID- 24448296
TI  - Aspirin intake correlates with halted growth of sporadic vestibular schwannoma in
      vivo.
AB  - OBJECTIVE: Given the presence of a pathological immune response in sporadic
      vestibular schwannoma (sVS), this study aims to explore the roles of aspirin in
      minimizing sVS growth in vivo. STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary care hospital. PATIENTS: People diagnosed with sVS and followed at a
      tertiary referral center by serial magnetic resonance imaging (MRI) for at least
      4 months within the period of January 1980 through April 2012. MAIN OUTCOME
      MEASURES: Patient use of aspirin and sVS growth rate measured by changes in the
      largest tumor dimension as noted on serial MRIs RESULTS: Within a set of 689
      cases, 347 were followed by serial MRI scans (50.3%); of the latter, 81 took
      aspirin, of which, 33 demonstrated sVS growth, and 48 did not. Of the 266
      nonaspirin users, 154 demonstrated sVS growth, and 112 did not. A significant
      inverse association was found among aspirin users and sVS growth (odds ratio
      [OR]: 0.50, 95% confidence interval [CI]: 0.29-0.85), which was not confounded by
      age or sex. CONCLUSION: Our results suggest a potential therapeutic role of
      aspirin in inhibiting sVS growth.

PMID- 24448297
TI  - Genetic variants of CDH23 associated with noise-induced hearing loss.
AB  - OBJECTIVES: Noise-induced hearing loss (NIHL) is a complex disease resulting from
      the interaction between external and intrinsic/genetic factors. Based on mice
      studies, one of the most interesting candidate gene for NIHL susceptibility is
      CDH23-encoding cadherin 23, a component of the stereocilia tip links. The aim of
      this study was to analyze selected CDH23 single nucleotide polymorphisms (SNPs)
      and to evaluate their interaction with environmental and individual factors in
      respect to susceptibility for NIHL in humans. METHODS: A study group consisted of
      314 worst-hearing and 313 best-hearing subjects exposed to occupational noise,
      selected out of 3,860 workers database. Five SNPs in CDH23 were genotyped using
      real-time PCR. Subsequently, the main effect of genotype and its interaction with
      selected environmental and individual factors were evaluated. RESULTS: The
      significant results within the main effect of genotype were obtained for the SNP
      rs3752752, localized in exon 21. The effect was observed in particular in the
      subgroup of young subjects and in those exposed to impulse noise; CC genotype was
      more frequent among susceptible subjects, whereas genotype CT appeared more often
      among resistant to noise subjects. The effect of this polymorphism was not
      modified by none of environmental/individual factors except for blood pressure;
      however, the latter one should be further investigated. Smoking was shown as an
      independent factor determining NIHL development. CONCLUSION: The results of this
      study confirm that CDH23 genetic variant may modify the susceptibility to NIHL
      development in humans, as it was earlier proven in mice. Because the differences
      between the 2 study groups were not necessarily related to susceptibility to
      noise but they also were prone to age-related cochlear changes, these results
      should be interpreted with caution until replication in another population.

PMID- 24448298
TI  - Clinical outcome parameters for necrotizing otitis externa.
AB  - OBJECTIVE: To investigate the duration of time elapsed between the onset of
      symptoms for necrotizing external otitis (NEO) and admission to hospital that may
      play a role in patient outcome. STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: Fourteen consecutive male patients with NEO
      with no improvement from the previous course of antibiotherapy and with findings
      of osteomyelitis on temporal bone CT, MRI, and positive detection of Tc-99m
      methylene diphosphonate on temporal bone, admitted as inpatients between 2008 and
      2012. INTERVENTION(S): Medical treatment of NEO and surgical debridement. MAIN
      OUTCOME MEASURE(S): Patients were divided into 2 groups according to median time
      elapsed between onset of symptoms and hospitalization (<30 d or >30 d). HbA1c,
      fasting blood sugar, erythrocyte sedimentation rate, C-reactive protein, pain
      intensity, radiologic grade, improvement since diagnosis, and total time to cure
      were compared according to the groups. The relationships between the laboratory
      data were analyzed to determine the parameters associated with time to recovery.
      RESULTS: Otalgia was significantly worse in patients who were admitted to
      hospital greater than 30 days after symptom onset (Mann-Whitney U test, p <
      0.002). Blood glucose increased related to delayed admission time (p < 0.001).
      CRP results were independently elevated from the admission time (p < 0.112).
      There was a statistically significant difference between groups according to ESR
      levels and recovery time (Mann-Whitney U test, p < 0.004 and p < 0.01). There was
      a positive correlation between HbA1c levels and recovery time in Group 1 and
      between ESR levels and recovery time in Group 2 (r = 0.872, p = 0.044; r = 0.630,
      p = 0.039). CONCLUSION: Clinical, laboratory, and outcome data worsen later than
      30 days in NEO.

PMID- 24448299
TI  - Commentary on Luis et al "Spontaneous plugging of the horizontal semicircular
      canal with reversible canal dysfunction and recovery of vestibular evoked
      myogenic potentials" (Otology and Neurotology 2013, DOI:
      10.1097/MAO.0b013e318287f343).

PMID- 24448301
TI  - Measuring the forces of middle ear surgery; evaluating a novel force-detection
      instrument.
AB  - HYPOTHESIS: The forces applied to the middle ear structures during surgery are
      measurable. BACKGROUND: Surgical forces applied to the middle ear are often cited
      as a cause of postoperative sensorineural hearing loss; however, no literature
      exists on how much total force is applied during common middle ear procedures.
      METHODS: Using our novel middle ear surgical force sensor, we took measurements
      from 6 temporal bones of common middle ear manipulations. RESULTS: Temporal bones
      of 3 males and 3 females yielded 72 measurements for an average peak applied
      force and 68 measurements for total applied force across 3 levels of operator
      experience. Statistically significant differences were seen between different
      levels of operator and how much force was applied, with senior operators using
      less force. CONCLUSION: We show it is possible to measure the applied forces in
      middle ear surgery and that some of these forces are very large. Larger forces
      are seen in destructive procedures and in procedures performed by inexperienced
      operators. This project is an important first step in investigating the
      association between surgically applied middle ear forces and postoperative
      sensorineural hearing loss.

PMID- 24448300
TI  - Reply to the Commentary on Luis et al. "Spontaneous plugging of the horizontal
      semicircular canal with reversible canal dysfunction and recovery of vestibular
      evoked myogenic potentials".

PMID- 24448302
TI  - In vivo imaging of mouse cochlea by optical coherence tomography.
AB  - HYPOTHESIS: Cochlear pathology can be evaluated in living animals using optical
      coherence tomography (OCT). BACKGROUND: The current imaging methods available for
      the detailed analysis of cochlear pathology in a clinical setting provide only
      limited information. Thus, a cochlear imaging modality with high definition is
      needed for improving the diagnosis of cochlear pathology. OCT has been used in
      other fields for obtaining high-resolution subsurface images, and its use could
      potentially be extended to the analysis of cochlear pathogenesis. METHODS:
      Slc26a4(-/-) mice, which generate endolymphatic hydrops, and their littermates
      were used in this study. Auditory function was monitored by the auditory
      brainstem responses (ABR). After the mice were placed under general anesthesia,
      OCT images of the cochlea were captured. The cochlea was subsequently dissected
      out and histologically evaluated. Three or 7 days later, the wild-type mice
      cochleae were visualized again. RESULTS: In ABR assessments, Slc26a4(-/-) mice
      showed severe hearing loss, while no significant hearing loss was found in
      Slc26a4(+/-) or Slc26a4(+/+) mice. OCT demonstrated normal morphology in the
      cochlea of both Slc26a4(+/-) and Slc26a4(+/+) mice, including the location of
      Reissner's membrane. Meanwhile, in Slc26a4(-/-) mice, obvious dislocation of
      Reissner's membrane was observed, indicating severe endolymphatic hydrops. These
      findings in the OCT images were consistent with the histologic results for the
      cochlear morphology, as observed with hematoxylin and eosin staining. Three or 7
      days later, wild-type cochleae were successfully visualized using OCT, and no
      otitis media or labyrinthitis was observed. CONCLUSION: OCT can be applied in the
      detection of endolymphatic hydrops in living mice, indicating the potential of
      OCT for cochlear imaging analyses for clinical use in the near future.

PMID- 24448303
TI  - Effective lung cancer screening is possible.

PMID- 24448308
TI  - Evaluation of DGT as a long-term water quality monitoring tool in natural waters;
      uranium as a case study.
AB  - The performance of the diffusive gradient in thin film technique (DGT) was
      evaluated as a tool for the long-term monitoring of water quality, using uranium
      as a case study. DGTs with a MetsorbTM (TiO2) sorbent were deployed consecutively
      at two alkaline freshwater sites, the River Enborne and the River Lambourn, UK
      for seven-day intervals over a five-month deployment period to obtain time
      weighted average concentrations. Weekly spot samples were taken to determine
      physical and chemical properties of the river water. Uranium was measured in
      these spot samples and after extraction from the DGT devices. The accuracy of the
      DGT device time weighted average concentrations to averaged spot water samples in
      both rivers was 86% (27 to 205%). The DGT diffusive boundary layer (DBL) (0.037
      0.141 cm - River Enborne and 0.062-0.086 cm - River Lambourn) was affected by
      both water flow and biofouling of the diffusion surface. DBL thicknesses found at
      both sites were correlated with flow conditions with an R(2) value of 0.614.
      Correlations were also observed between the DBL thickness and dissolved organic
      carbon (R(2) = 0.637) in the River Lambourn, indicating the potential presence of
      a complex zone of chemical interactions at the surface of the DGT. The range of
      DBL thicknesses found at the River Lambourn site were also attributed to of the
      development of macro-flora on the active sampling surface, indicating that the
      DBL thickness cannot be assumed to be water flow dependant only. Up to a 57%
      under-estimate of uranium DGT concentration was observed compared to spot sample
      concentrations if the DBL was neglected. This study has shown that the use of DGT
      can provide valuable information in environmental monitoring schemes as part of a
      'tool-box' approach when used alongside conventional spot sampling methods. 

PMID- 24448309
TI  - Levels of plasma matrix metalloproteinases (MMP-2 and MMP-9) in response to
      INTEGRA(r) dermal regeneration template implantation.
AB  - BACKGROUND: Cutaneous wound healing results in scar formation. Matrix
      metalloproteinases (MMP) transform extracellular matrix proteins and modulate
      inflammation and cell signaling, thus determining scar outcome. To provide rapid
      wound closure and reduced scarring, dermal scaffolds were introduced. Little is
      known about the influence of these materials on MMPs levels. MATERIAL AND
      METHODS: In this in vivo study the levels of MMP-2, MMP-9, and mediators of
      inflammation and fibrosis (IL-4 and TGF-beta1) in patients treated with
      Integra(r) dermal regeneration template (IDRT) were investigated. In the group of
      11 pediatric patients treated with IDRT, levels of selected molecules were
      analyzed before surgery and at day 1, 7, and 25 after scaffold implantation.
      RESULTS: The mean IDRT take rate was 89.5 +/- 4.7% with 4 patients (36%) who
      developed local infection. Patients were divided into 2 groups according to
      presence of infection (1 group with complications and 1 group without
      complications). In the group with complications, the IDRT take rate was
      significantly reduced compared to the group without complications (71.5 +/- 5.4
      vs. 100 +/- 0.1; p<0.005). Plasma levels of MMP-2 were significantly (p<0.05)
      elevated in both groups on day 7 after the scaffold placement compared to
      baseline. Positive correlations between IL-4 and MMP-2 (p=0.01) in the group with
      complications and TGF-beta1 and MMP-9 (p=0.012) in both groups were observed.
      CONCLUSIONS: These findings suggest that Integra(r) scaffold degradation is
      mainly caused by MMP-2, whereas inflammation associated with local infection
      increases levels of this molecule and it is not associated with elevation of MMP
      9. This shows that dermal regeneration with Integra(r) uses molecular mechanisms
      other than scar formation during dermal wound healing.

PMID- 24448310
TI  - Age estimation using level of eyebrow and eyelash whitening.
AB  - BACKGROUND: The aim of this study was to determine whether eyebrow and eyelash
      whitening is an effective parameter in age estimation. MATERIAL AND METHODS: We
      evaluated 1545 patients. Age groups were 1-10, 11-20, 21-30, 31-40, 41-50, 51-60,
      61-70, 71-80, and 81-90 years. Level of whitening was categorized as level 0: no
      whitening, level 1: 1-3 strands, level 2: 3-10 strands, level 3: 10 strands-2/3
      whitening, level 4: >3/4 whitening. RESULTS: Mean age was 42.39 +/- 20.01. While
      there was no eyebrow whitening in 87% of the subjects, level 4 whitening of
      eyebrows was observed in 0,8% of the subjects. There was no eyelash whitening in
      97,7% of the subjects and no level 4 eyelash whitening was detected in any
      subject. Men had significantly more level 1, 2, 3, and 4 eyebrow whitening
      compared with women. There was no gender difference in terms of eyelash whitening
      level. There was no eyebrow and eyelash whitening in subjects age 1-40 years;
      whitening began in the 41-50 years age group and increased with age in other
      groups. Mean age was 39.59 +/- 19.63 years in subjects with no eyebrow whitening;
      59 years in level 1, 61 years in level 2, 63 years in level 3, and 69 years in
      level 4 eyebrow whitening. Mean age was 41.85 +/- 19.87 in subjects with no
      eyelash whitening; and 63.57 +/- 10.75 in those with whitening. CONCLUSIONS:
      Particularly after 41-50 years of age, level of eyebrow and eyelash whitening may
      be among a useful age estimation parameter.

PMID- 24448311
TI  - People with older age and lower FEV1%pred tend to have a smaller FVC than VC in
      pre-bronchodilator spirometry.
AB  - We enrolled 1772 subjects who underwent pulmonary function test before
      preoperative examination in our study. Pre-bronchodilator forced expiratory
      volume in one second (FEV1), vital capacity (VC) and forced vital capacity (FVC)
      were measured as primary data. According to the numerical relationship between
      VCmax and FVC, two groups were divided: VCmax>FVC and VCmax=FVC. Age, gender,
      height, weight, BMI and FEV1/FVC, FEV1%pred, FEV1/VCmax were compared between the
      two groups. Using multivariate logistic regression, factors related to
      classification of VCmax=FVC or VCmax>FVC were estimated. Of the 1772 spirometric
      results analyzed, 614 (34.65%) with VCmax=FVC and 1158 (65.35%) with VCmax>FVC
      were identified. Compared to VCmax=FVC group, subjects in VCmax>FVC group have
      older age (95%CI [1.50, 3.99], P<0.001), lower FEV1%pred (95%CI [-12.22, -8.07],
      P<0.001) and lower FEV1/VCmax (95%CI [-0.07, -0.05], P<0.001), parameters such as
      height, weight, BMI, FEV1/FVC showed no statistical significance. We made a
      conclusion that people with older age and lower FEV1%pred tend to have a smaller
      FVC than VC in pre-bronchdilator spirometry. 

PMID- 24448312
TI  - An easily accessible carbon material derived from carbonization of
      polyacrylonitrile ultrathin films: ambipolar transport properties and application
      in a CMOS-like inverter.
AB  - Ultrathin carbon films were prepared by carbonization of a solution processed
      polyacrylonitrile (PAN) film in a moderate temperature range (500-700  degrees
      C). The films displayed balanced hole (0.50 cm(2) V(-1) s(-1)) and electron
      mobilities (0.20 cm(2) V(-1) s(-1)) under ambient conditions. Spectral
      characterization revealed that the electrical transport is due to the formation
      of sp(2) hybridized carbon during the carbonization process. A CMOS-like inverter
      demonstrated the potential application of this material in the area of carbon
      electronics, considering its processability and low-cost. 

PMID- 24448313
TI  - Pregnancy as a cardiac stress model.
AB  - Cardiac hypertrophy occurs during pregnancy as a consequence of both volume
      overload and hormonal changes. Both pregnancy- and exercise-induced cardiac
      hypertrophy are generally thought to be similar and physiological. Despite the
      fact that there are shared transcriptional responses in both forms of cardiac
      adaptation, pregnancy results in a distinct signature of gene expression in the
      heart. In some cases, however, pregnancy can induce adverse cardiac events in
      previously healthy women without any known cardiovascular disease. Peripartum
      cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy.
      To understand how pregnancy can cause heart disease, it is first important to
      understand cardiac adaptation during normal pregnancy. This review provides an
      overview of the cardiac consequences of pregnancy, including haemodynamic,
      functional, structural, and morphological adaptations, as well as molecular
      phenotypes. In addition, this review describes the signalling pathways
      responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also
      compare and contrast cardiac adaptation in response to disease, exercise, and
      pregnancy. The comparisons of these settings of cardiac hypertrophy provide
      insight into pregnancy-associated cardiac adaptation. 

PMID- 24448316
TI  - Asian pollution climatically modulates mid-latitude cyclones following
      hierarchical modelling and observational analysis.
AB  - Increasing levels of anthropogenic aerosols in Asia have raised considerable
      concern regarding its potential impact on the global atmosphere, but the
      magnitude of the associated climate forcing remains to be quantified. Here, using
      a novel hierarchical modelling approach and observational analysis, we
      demonstrate modulated mid-latitude cyclones by Asian pollution over the past
      three decades. Regional and seasonal simulations using a cloud-resolving model
      show that Asian pollution invigorates winter cyclones over the northwest Pacific,
      increasing precipitation by 7% and net cloud radiative forcing by 1.0 W m(-2) at
      the top of the atmosphere and by 1.7 W m(-2) at the Earth's surface. A global
      climate model incorporating the diabatic heating anomalies from Asian pollution
      produces a 9% enhanced transient eddy meridional heat flux and reconciles a
      decadal variation of mid-latitude cyclones derived from the Reanalysis data. Our
      results unambiguously reveal a large impact of the Asian pollutant outflows on
      the global general circulation and climate.

PMID- 24448315
TI  - Opposing roles of Akt and STAT3 in the protection of the maternal heart from
      peripartum stress.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM) is a pregnancy-associated
      cardiomyopathy in previously healthy women. Mice with a cardiomyocyte-restricted
      deletion of signal transducer and activator of transcription-3 (STAT3, CKO)
      develop PPCM. PI3K-Akt signalling is thought to promote cardiac hypertrophy and
      protection during pregnancy. We evaluated the role of activated Akt signalling in
      the maternal heart postpartum. METHODS AND RESULTS: CKO mice were bred to mice
      harbouring an Akt transgene, specifically expressed in cardiomyocytes (CAkt(tg))
      generating CKO; CAkt(tg), CAkt(tg), CKO, and wild-type sibling mice. CAkt(tg) and
      CKO;CAkt(tg) female mice developed PPCM with systolic dysfunction. Both genotypes
      displayed cardiac hypertrophy and lower capillary density, showed increased
      phosphorylation of p66 Src homology 2 domain containing protein and FoxO3A, and
      reduced expression of manganese superoxide dismutase as well as increased
      cathepsin D activity and increased miR-146a levels [indicative for generation of
      the anti-angiogenic 16 kDa prolactin (PRL)]. Cardiac inflammation and fibrosis
      was accelerated in CKO;CAkt(tg) and associated with high postpartum mortality.
      The PRL blocker, bromocriptine (BR), prevented heart failure and the decrease in
      capillary density in CKO;CAkt(tg) and CAkt(tg) mice. BR attenuated high
      mortality, up-regulation of CCL2, and cardiac inflammation as well as fibrosis in
      CKO;CAkt(tg). PRL infusion induced cardiac inflammation in CKO;CAkt(tg)
      independent of pregnancy. In neonatal rat cardiomyocytes, PRL and interferon
      gamma (IFNgamma) induced the expression of CCL2 via activation of Akt.
      CONCLUSION: Postpartum Akt activation is detrimental for the peripartum heart as
      it lowers anti-oxidative defence and in combination with low STAT3 conditions,
      accelerate cardiac inflammation and fibrosis. PRL and its cleaved 16 kDa form are
      central for Akt-induced PPCM as indicated by the protection from the disease by
      PRL blockade.

PMID- 24448314
TI  - Maternal cardiac metabolism in pregnancy.
AB  - Pregnancy causes dramatic physiological changes in the expectant mother. The
      placenta, mostly foetal in origin, invades maternal uterine tissue early in
      pregnancy and unleashes a barrage of hormones and other factors. This foetal
      'invasion' profoundly reprogrammes maternal physiology, affecting nearly every
      organ, including the heart and its metabolism. We briefly review here maternal
      systemic metabolic changes during pregnancy and cardiac metabolism in general. We
      then discuss changes in cardiac haemodynamic during pregnancy and review what is
      known about maternal cardiac metabolism during pregnancy. Lastly, we discuss
      cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the
      potential contribution of aberrant cardiac metabolism to disease aetiology. 

PMID- 24448320
TI  - TaMDHAR4, a monodehydroascorbate reductase gene participates in the interactions
      between wheat and Puccinia striiformis f. sp. tritici.
AB  - Reactive oxygen species (ROS) in plants are induced in various cellular
      compartments upon pathogen infection and act as an early signal during plant
      pathogen interactions. Monodehydroascorbate reductase (MDHAR) is involved in
      plant disease resistance through the regulation of the ROS level via the
      ascorbate-glutathione (AsA-GSH) cycle. In this study, TaMDHAR4 was firstly
      isolated from wheat cultivar Suwon 11, and this protein exhibits high similarity
      to MDHAR proteins from other plant species. Bioinformatics analyses indicated
      that TaMDHAR4 contains typical structural features, such as mPTS-like sequences
      in the C-terminal extension and trans-membrane domain followed by five basic
      arginine residues (-RKRRR), which predicted that this protein may be localized in
      the peroxisome. qRT-PCR analyses demonstrated that TaMDHAR4 could be induced by
      various exogenous hormones, such as ABA, MeJA, and ETH. TaMDHAR4 is sharply down
      regulated at 12 and 18 hpi only in wheat leaves challenged with Puccinia
      striiformis f. sp. tritici (Pst) race CYR23 and induced at 48 hpi with both Pst
      races CYR23 and CYR31. SOD and APX injection analyses demonstrated that TaMDHAR4
      may be involved in the interaction between wheat and Pst through the regulation
      of its expression. Moreover, the knockdown of TaMDHAR4 through virus-induced gene
      silencing (VIGS) enhanced the wheat resistance to Pst by inhibiting sporulation
      in the compatible interaction. Histological observations also demonstrated that
      silenced wheat resulted in an increased proportion of necrotic area at the
      infection sites and suppressed Pst hypha elongation. The study provided novel
      insights into the molecular functions of TaMDHAR4 during plant-pathogen
      interactions.

PMID- 24448321
TI  - Overexpression of TaNHX3, a vacuolar Na+/H+ antiporter gene in wheat, enhances
      salt stress tolerance in tobacco by improving related physiological processes.
AB  - Salt stress is one of the major abiotic stresses affecting plant growth,
      development, and productivity. In this study, we functionally characterized a
      wheat vacuolar Na(+)/H(+) antiporter gene (TaNHX3). TaNHX3 is 78.9% identical
      with TaNHX2 in nucleic acid level, encoding a polypeptide of 522 amino acids
      (aa). TaNHX3 is targeted onto tonoplast after ER sorting and can complement the
      growth under salt stress in a yeast mutant with a defective vacuolar Na(+)/H(+)
      antiporter exchange. TaNHX3 transcripts were induced by applying salt stress in
      wheat cultivars. More TaNHX3 were detected in the salt-stress-resistant cultivar
      Ji 7369 compared with the salt-stress-sensitive cultivar Shimai 12 and Ji-Shi-3,
      an isogenic line derived from aforementioned cultivars with Shimai 12 genetic
      background. The ectopic TaNHX3 expression in tobacco significantly enhanced the
      plant tolerance to salt stress. Compared with control plants, the TaNHX3
      overexpressing plants displayed no varied Na(+) contents and accumulated more
      Na(+) amount in plants. However, they exhibited higher fresh and dry weights,
      more accumulative nitrogen, phosphorus, and potassium, higher contents of
      chlorophyll, carotenoid, soluble protein, higher activities of the antioxidant
      enzymes including superoxide dismutase, catalase, and peroxidase, and lower
      malondialdehyde and H2O2 amount. Our results indicated that TaNHX3 plays an
      important role in regulating the cytosolic Na(+) transportation within vacuoles
      under high salinity, alleviating the Na(+) damage effects. The improved salt
      stress tolerance in TaNHX3 overexpressing tobacco plants is closely associated
      with the improvement of the aforementioned physiological processes. TaNHX3 can be
      used as a candidate gene for molecular breeding of salt-tolerant plants. 

PMID- 24448322
TI  - Transcriptional regulation of 9-cis-epoxycarotenoid dioxygenase (NCED) gene by
      putrescine accumulation positively modulates ABA synthesis and drought tolerance
      in Lotus tenuis plants.
AB  - The accumulation of putrescine (Put) and increased arginine decarboxylase (ADC,
      EC 4.1.1.19) activity levels in response to osmotic stress has been reported;
      however, the biological meaning of this increase remains unclear. To obtain new
      insights into these questions, we studied the drought response of a transgenic
      Lotus tenuis line that expresses the oat ADC gene, which is driven by the stress
      inducible pRD29A promoter. This line contains high levels of Put with no changes
      in spermidine and spermine contents, even under water deficits. Our results
      indicate that the biochemical and morphological responses to dehydration
      correlate with the Put level and provide evidence that Put controls the ABA
      content in response to drought by modulating ABA biosynthesis at the
      transcriptional level. 

PMID- 24448323
TI  - Somatic deletions implicated in functional diversity of brain cells of
      individuals with schizophrenia and unaffected controls.
AB  - While somatic DNA copy number variations (CNVs) have been identified in multiple
      tissues from normal people, they have not been well studied in brain tissues from
      individuals with psychiatric disorders. With ultrahigh depth sequencing data, we
      developed an integrated pipeline for calling somatic deletions using data from
      multiple tissues of the same individual or a single tissue type taken from
      multiple individuals. Using the pipelines, we identified 106 somatic deletions in
      DNA from prefrontal cortex (PFC) and/or cerebellum of two normal controls
      subjects and/or three individuals with schizophrenia. We then validated somatic
      deletions in 18 genic and in 1 intergenic region. Somatic deletions in BOD1 and
      CBX3 were reconfirmed using DNA isolated from non-pyramidal neurons and from
      cells in white matter using laser capture microdissection (LCM). Our results
      suggest that somatic deletions may affect metabolic processes and brain
      development in a region specific manner. 

PMID- 24448324
TI  - Loss of GATA3 in bladder cancer promotes cell migration and invasion.
AB  - The transcription factor GATA3 is known as a breast tumor suppressor as well as a
      urothelial marker, and its loss is often seen in high-grade invasive bladder
      cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely
      unknown. In this study, we assessed the effects of GATA3 silencing via RNA
      interference on cell migration, invasion, and proliferation of bladder cancer.
      GATA3 expression was downregulated in all four bladder cancer lines examined,
      compared with a non-neoplastic urothelial line SVHUC. Knockdown of GATA3 in the
      bladder cancer lines (5637, TCC-SUP, J82) resulted in promotion of cell migration
      and invasion as well as increases in the expression of their related molecules,
      such as vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and
      MMP-9, and the activity of MMP-2 and MMP-9. GATA3 loss was also associated with
      an increasing level of a mesenchymal marker N-cadherin and a decreasing level of
      an epithelial marker beta-catenin. Consistent with these findings, enforced
      expression of GATA3 in UMUC3 inhibited cell migration and invasion. However,
      GATA3 showed marginal effects on bladder cancer cell viability and the expression
      of cell cycle- or apoptosis-related molecules. Additionally, in contrast to
      bladder cancer lines, no significant effects of GATA3 silencing on cell migration
      were seen in SVHUC. These findings suggest that GATA3 plays an important role in
      the prevention of bladder cancer progression and metastasis by inhibiting cell
      migration and invasion as well as epithelial-to-mesenchymal transition.

PMID- 24448325
TI  - Direct photodegradation of lamotrigine (an antiepileptic) in simulated sunlight-
      pH influenced rates and products.
AB  - Lamotrigine is an antiepileptic and mood stabilizing drug that has been detected
      in wastewater, groundwater, surface water and drinking water, at frequencies in
      surface water ranging from 47 to 97%. Because lamotrigine is a weak base (pKa =
      5.7) that appears in two protonation states in natural waters, this study
      examined the direct photodegradation of lamotrigine (11.4 to 12.0 mg L(-1)) in
      simulated sunlight using liquid chromatography-UV diode array detection and
      buffered aqueous solutions at pH 3.3, 5.3, and 7.7. Lamotrigine's half-life
      varied little (100 +/- 3 to 112 +/- 2 h) with solution pH, but its specific light
      absorption rate was 12 times higher, and its reaction quantum yield was 13 times
      lower, at pH 7.7 versus pH 3.3. In the estimated midday, midsummer sunlight in
      Denver, CO, USA (latitude 39.8617  degrees N), lamotrigine's estimated
      photodegradation rate was more than twice as fast at pH 7.7 versus pH 3.3.
      Lamotrigine's photoproducts were detected by liquid chromatography-UV diode array
      detection and time-of-flight mass spectrometry. Solution pH was shown to affect
      the identities and relative abundances of lamotrigine's photoproducts. Some
      photoproducts appeared only in solutions containing protonated lamotrigine, and
      others appeared only in solutions containing neutral lamotrigine. As a result,
      different reaction mechanisms were proposed. Finally, lamotrigine's reaction
      quantum yield (2.51 +/- 0.07 * 10(-5) mol einstein(-1) at pH 7.7) and other
      results suggested that lamotrigine and three photoproducts are approximately as
      resistant to direct photodegradation as carbamazepine, a frequently detected
      pharmaceutical in surface waters. 

PMID- 24448326
TI  - Evaluation of a pharmacist-managed methadone taper*.
AB  - OBJECTIVES: To evaluate the efficacy of a pharmacist-managed methadone taper as
      compared to previous prescribing practices. DESIGN: Retrospective chart review
      with comparison to historical controls. SETTING: Ninety-six-bed pediatric
      quaternary care facility with the majority of the patients in a 24-bed ICU.
      PATIENTS: Thirty-two patients, 1 month to 16 years old, weaned off opioids using
      methadone prior to protocol initiation were compared with 20 patients, 1 month to
      15 years old, weaned per the pharmacist-managed methadone taper protocol.
      INTERVENTIONS: Implementation of a pharmacist-managed methadone tapering
      protocol. MEASUREMENTS AND MAIN RESULTS: Patient age, gender, weight, and risk of
      withdrawal were similar between the groups (p = not significant). The average
      taper length before pharmacist intervention was 24.7 days; after implementation
      it was 15 days (p = 0.0026). There was no statistical difference in the number of
      additional doses of opioid required or withdrawal scores between the populations.
      Opioid infusions were stopped, on average, 1.54 days sooner in the intervention
      group (p = 0.0039). A decrease in hospital length of stay was also seen in the
      intervention group (p = 0.023). CONCLUSIONS: A pharmacist-managed protocolized
      methadone taper facilitates discontinuing methadone sooner, discontinuing
      additional opioid infusions sooner, and may impact on the length of hospital
      stay. The protocol developed at the University of Minnesota Amplatz Children's
      Hospital has demonstrated that it is an effective method to wean pediatric
      patients from opioids.

PMID- 24448327
TI  - Why do we need to care about tumor location in the patient with colorectal
      cancer?

PMID- 24448328
TI  - The influence of increased fluid intake in the prevention of urinary stone
      formation: a systematic review.
AB  - AIM: to assess whether the volume of fluid intake influence the prevention of
      urinary stone formation. METHODS: a systematic review from MEDLINE Electronic
      database was conducted. All of the controlled trial (RCT), case-control, and
      cohort studies written in English language were included in the study. Data
      analysis was performed to the design of the study, volume of fluid intake (higher
      volume as experimental group and lower volume as control group), and risk of
      stone formation. All of the included studies were appraised using the Oxford
      Center for Evidence-based Medicine appraisal tool for therapy (Randomized
      Controlled Trial) and level of evidence. RESULTS: our systematic review included
      five studies (1 RCT and case-control study in patients with history of
      urolithiasis, and 3 prospective cohorts in patients without history of
      urolithiasis). Three studies increased fluid intake to 2.5 Liters/day and one
      study to 2 Liters/day, while one other study used the urine production target of
      2 Liters/day. All of these studies showed that increased fluid intake per day
      could decrease the risk of both primary and secondary stone formation.
      CONCLUSION: stronger evidence are still needed to conclude that increasing fluid
      intake could be utilized as a strategy to prevent primary urolithiasis because of
      the lack of data from the clinical trials supporting it. However, to prevent the
      recurrence of urolithiasis, increasing fluid intake could be recommended with the
      urine volume target of more than 2,000 mL/day.

PMID- 24448329
TI  - The efficacy of zinc for treatment of chronic prostatitis.
AB  - AIM: to investigate the efficacy of zinc supplementation in chronic prostatitis
      treatment. METHODS: present randomized clinical trial was conducted on 120
      patients with diagnosis of chronic prostatitis (IIIA NIH) after preliminary
      evaluation and ruling out other conditions. The study group received oral zinc
      sulfate 220 mg daily as capsule without any other supplements. The control group
      received placebo. Subjects were examined for NIH-CPSI scores every 4 weeks for 12
      weeks. RESULTS: 101 subjects completed the study. There were no statistically
      significant differences in scores and sub-scores of NIH-CPSI between groups
      before intervention. Decline in the score and sub-scores were more prominent in
      case group after beginning of the study; though the differences were not
      statistically significant. Furthermore, the differences in total score and pain
      score at 12 weeks follow was statistically significant (p=0.003 and p=0.02,
      respectively). CONCLUSION: zinc supplements may benefit in management of patients
      with chronic prostatitis NIH-IIIA. It can be attributable to anti-bacterial and
      immuno-modulatory functions of organic zinc in the body.

PMID- 24448330
TI  - Profile of food and nutrient intake among Indonesian elderly population and
      factors associated with energy intake: a multi-centre study.
AB  - AIM: to obtain profile of food and nutrient intake in Indonesian elderly
      population and factors associated with energy intake. METHODS: multi-center cross
      sectional study in 13 hospitals across Indonesia was conducted among 387 elderly
      who had attended geriatric clinics. Data collected including demographic
      characteristics, functional status, cognitive status, mental status, nutritional
      status, food intake, present activities, and data on chronic diseases. Chi square
      and logistic regression tests were performed to analyze the data. RESULTS: most
      of subjects (58.4%) were women and had educational background senior high school
      or higher degree (61.1%). The average of energy intake was 1266.74 (336.51)
      kilocalories. Calcium and protein intake were below the recommended of dietary
      allowance. female sex (OR 0.23; 95% CI 0.139-0.390) and osteoporotic subjects (OR
      0.48; 95% CI 0.25-0.93) have lower risk for having <80% RDA daily energy intake,
      while lower educational level (OR 1.96; 95% CI 1.21-3.18) has higher risk for
      having <80% RDA daily energy intake. CONCLUSION: total energy intake were
      inadequate in the elderly. Female sex and osteoporotic subjects have lower risk
      for having <80% RDA daily energy intake, while lower educational level has higher
      risk for having <80% RDA daily energy intake.

PMID- 24448331
TI  - Adenomatous Polyposis Coli, mismatch repair, and microsatellite instability in
      colorectal cancer based on different locations.
AB  - AIM: to examine the protein expression negative (PEN) of Adenomatous Polyposis
      Coli (APC), Mismatch Repair (MMR), and Microsatellite Instability (MSI) status of
      colorectal cancer (CRC), and establish a comparison of those molecular
      characteristics in CRC location among Indonesian patients in Adam Malik Hospital,
      Pirngadi Hospital, and other hospitals within the network of Faculty of Medicine
      University of Sumatera Utara Medan Indonesia. METHODS: this prospective study was
      conducted from April to December 2012. Fresh tissues were obtained from
      colorectal tumor patients. The APC-PEN, MMR (MLH1, MSH2, PMS2, MSH6)-PEN, were
      assessed by immunohistochemistry, and MSI by PCR using 5 microsatellite markers
      (BAT25, BAT26, D2S123, D5S346, D17S250), as independent variables. The tumour
      locations as dependent variables were divided into proximal colon (caecum,
      ascending colon, transverse colon); distal colon (splenic flexure, descending
      colon, sigmoid) and rectum. The comparative study were done by bivariate and
      multivariate analysis. RESULTS: there were 77 cases of colorectal adenocarsinoma.
      MMR-PEN was found in 54 of 77 (70.1%). MLH1-PEN was different between distal
      colon and rectal cancer (p=0.008); MSH6-PEN was different between proximal colon
      and rectal cancer (p= 0.020). Multivariate analysis showed: MLH1-PEN was related
      to cancer location (p=0.006) with OR 0.12 (95% CI 0.026-0.547). It had 0.12 times
      probability to be found in distal than rectum. MLH1-PEN had 10 times higher
      probability to be found in proximal than in distal (p=0.037). MSH6-PEN was
      related to the location (p=0.026) with OR 0.165 (95% CI 0.034-0.803), and had
      0.165 times probability to be found in proximal than rectum; and 11 times higher
      probability in distal than proximal colon (p=0.043). APC-PEN was related to the
      location (p=0.020), with OR 6.897 (95% CI 1.359-34.995), and 6.89 times higher
      probability in distal than in rectum, with other variables controlled. MSI-H was
      found in 29 of 77 (37.7%) and MSI-L/MSS in 48 (62.3%). The proportion of MSI-H
      displayed a tendency to occur in proximal rather than in distal colon or rectal
      cancer. CONCLUSION: the underlying carcinogenic pathway or molecular background
      differs according to the cancer locations of CRC patients in this region. MLH1
      PEN was prominent in proximal colon cancer, MSH6-PEN in distal colon and rectal
      cancer, and APC-PEN in distal colon respectively.

PMID- 24448332
TI  - Abdominal circumference in relation to body weight gain/loss in patients on
      chronic hemodialysis.
AB  - AIM: to determine a constant relationship between changes in abdominal
      circumference (in centimeter) and body weight (in kilogram) in chronic kidney
      disease (CKD) patients undergoing chronic hemodialysis. METHODS: experimental
      analytical study in patients with CKD on hemodialysis, using before and after
      treatment design at the Dialysis Unit of Cipto Mangunkusumo Hospital, Jakarta.
      The sample were selected consecutively. Weighing and abdominal circumference
      measurements were done at the time of before and after hemodialysis session on
      the same day. Repeated measurements were performed on different days in 104
      subjects to achieve the target sample size of 676. Serum albumin level were also
      measured on the patients. RESULTS: there was a strong (r=0.838) and significant
      (p=0.000) correlation between mean body weight and mean abdominal circumferences
      before and after hemodialysis. In the calculation of the regression between the
      mean body weight before and after hemodialysis (X) with a mean abdominal
      circumference before and after hemodialysis (Y), regression formula: Y=34.94 +
      0.84 X was obtained. There was no significant correlation between serum albumin
      levels (3.93+/-0.40 g/dL) and abdominal circumference before hemodialysis,
      abdominal circumference after hemodialysis, and the mean abdominal circumference
      before and after hemodialysis. CONCLUSION: prediction of weight changes in
      patients with CKD on chronic hemodialysis, can be measured through the abdominal
      circumference measurement before and after hemodialysis.

PMID- 24448333
TI  - VICTORY project: a study of counterfeit PDE5 inhibitor (sildenafil) in Indonesia.
AB  - AIM: to quantify the extent of counterfeit sildenafil in Indonesia. METHODS: the
      study was conducted in 4 big areas: Jakarta, Bandung, East Java (Surabaya and
      Malang), and Medan. Sildenafil 100 mg tablets were purchased from pharmacies,
      drugstores, street peddlers, and 3 Indonesian websites. The outlets were chosen
      by random sampling in each stratum (type of outlet). Sildenafil tablets purchased
      were sent to Pfizer Quality Operations Division, Dalian, China, for authenticity
      evaluations (by infra red spectral analysis). All counterfeit tablets were then
      sent to Pfizer Counterfeit Medicines Laboratory, Sandwich, UK, a portion of which
      were analyzed quantitatively for sildenafil concentration per tablet (by HPLC).
      RESULTS: a total of 518 sildenafil 100 mg tablets were collected and sent to
      Dalian. Of these tablets, 284 tablets (55%) were genuine sildenafil and 234
      tablets (45%) were counterfeit sildenafil. Counterfeit sildenafil were mostly
      found in street peddlers (100%), in drugstores (56%), and from internet (33%),
      but pharmacies also had (13%) counterfeit sildenafil. The sildenafil content of
      106 counterfeit tablets analyzed varied from 24 to 157 mg per 100 mg tablet. No
      analysis was done to determine other active ingredient. CONCLUSION: 45%
      sildenafil 100 mg tablets in Indonesia were found counterfeit and widely
      distributed in street peddlers, drugstores, and pharmacies. This report is aimed
      to alert the potential consumers, health professionals and regulators of this
      problem.

PMID- 24448334
TI  - Correlation between T2* cardiovascular magnetic resonance with left ventricular
      function and mass in adolescent and adult major thalassemia patients with iron
      overload.
AB  - AIM: to assess for a correlation between T2*CMR with LV function and mass in
      thalassemic patients with iron overload. METHODS: a cross-sectional study on
      thalassemic patients was conducted between July and September 2010 at Cipto
      Mangunkusumo and Premier Hospitals, Jakarta, Indonesia. Clinical examinations,
      review of medical charts, electrocardiography, echocardiography, and T2*CMR were
      performed. Cardiac siderosis was measured by T2*CMR conduction time. Left
      ventricle diastolic and systolic functions, as well as LV mass index were
      measured using echocardiography. Correlations between T2*CMR and echocardiography
      findings, as well as serum ferritin were determined using Pearson's and
      Spearman's tests. RESULTS: thirty patients aged 13-41 years were enrolled, of
      whom two-thirds had -thalassemia major and one-third had HbE/-thalassemia.
      Diastolic dysfunction was identified in 8 patients, whereas systolic function was
      normal in all patients. Increased LV mass index was found in 3 patients. T2*CMR
      conduction times ranged from 8.98 to 55.04 ms and a value below 20 ms was
      demonstrated in 14 patients. There was a statistically significant moderate
      positive correlation of T2*CMR conduction time with E/A ratio (r = 0.471, P =
      0.009), but no correlation was found with LV mass index (r=0.097, P=0.608). A
      moderate negative correlation was found between T2*CMR and serum ferritin (r = 
      0.514, P = 0.004), while a moderate negative correlation was found between serum
      ferritin and E/A ratio (r = -0.425, P = 0.019). CONCLUSION: T2*CMR myocardial
      conduction time has a moderate positive correlation with diastolic function,
      moderate negative correlation with serum ferritin, but not with LV mass index and
      systolic function.

PMID- 24448335
TI  - Cardiac involvement mimicking acute coronary syndrome in idiopathic
      hypereosinophilic syndrome.
AB  - Hypereosinophilic syndrome (HES) is defined as a persistent eosinophilia lasting
      longer than 6 months of unknown origin and related to organ involvement. Cardiac
      involvement, usually leading to morbidity and mortality of HES patients, often
      mimics other diseases such as acute coronary syndrome. We report a 46-year-old
      female who came to hospital with atypical chest pains and a known history of
      eosinophilia. After excluding other possible causes of eosinophilia, she
      underwent further cardiac investigations. She had normal cardiac size on
      echocardiography and no thrombus or mass, with only global hypokinesia with
      systolic and diastolic dysfunction noted. These findings were different from
      other studies. This patient was then treated as HES with cardiac involvement. 

PMID- 24448336
TI  - Pituitary apoplexy due to thyroxine therapy in a patient with congenital
      hypothyroidism.
AB  - A 24-year-old woman was admitted with general weakness, umbilical swelling,
      developmental delay, speech disorder, constipation, gait problem. Her findings
      were umbilical hernia, xerosis, dry hair, and short stature. After thyroxine
      treatment, she also had headache, vomiting, and palpitation, lack of appetite,
      and sleep disturbance. Pituitary magnetic resonance imaging revealed a
      heterogeneous mass at the central part of the gland on coronal section and it was
      interpreted as pituitary apoplexy. In the current case, the patient with
      congenital hypothyroidism (CH) developed pituitary apoplexy (PA) after thyroxine
      therapy. Therefore, it is suggested that the complaints were related to PA rather
      than adrenal insufficiency. Here we describe a case report evaluating PA in a
      patient with thyrotrophic pituitary adenoma due to CH. To the best of our
      knowledge, this is the first case in terms of PA associated with CH after
      thyroxine therapy in the literature. 

PMID- 24448337
TI  - Typhoid fever as a triggering factor in acute and intractable bronchial asthma
      attack.
AB  - Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia,
      typhoid fever is endemic with high incidence of the disease. In daily practice we
      frequently have patients with bronchial asthma, and it is becoming worse when
      these patients get typhoid fever. After oral ingestion, Salmonella typhi invades
      the the intestine mucosa after conducted by microbial binding to epithelial
      cells, destroying the microfold cells (M cell) then passed through the lamina
      propria and detected by dendritic cells (DC) which express a variety of pathogen
      recognition receptors on the surfaces, including Toll-Like Receptor (TLR).
      expressed on macrophages and on intestinal epithelial cells inducing degradation
      of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process
      initiates the induction of pro-inflammatory gene expression profile adhesion
      molecules, chemokines, adhesion molecules, and other proteins that induce and
      perpetuate the inflammation in host cells then will induce acute ant intractable
      attack of bronchial asthma. The role of typhoid fever in bronchial asthma,
      especially in persons with acute attack of bronchial asthma, is not well
      understood. In this article, we will discuss the role of typhoid fever in the
      bronchial asthma patients which may cause bronchial asthma significantly become
      more severe even triggering the acute and intractable attack of bronchial asthma.
      This fact makes an important point, to treat completely the typhoid fever in
      patients with bronchial asthma. 

PMID- 24448339
TI  - Science and the art of case reporting in medicine.
AB  - The case report is one type of article published in medical journals. Not all
      case reports can be published. Case reports worth publishing are case reports
      that have good teaching points and good clinical messages. Writing case reports
      need academic and clinical skills, along with a taste of art to interest readers
      to read and study about the case we report. Case reports are expected to be a
      good tool to all clinicians to build their clinical reasoning and sharpen their
      clinical instincts. 

PMID- 24448338
TI  - Successful treatment of discoid lupus erythematosus with chloroquine.

PMID- 24448340
TI  - Less invasive mechanical ventilation strategies in ARDS: the future?
AB  - The last very-successful management of mechanical ventilation was in 2000 when
      application of low tidal volume and moderate pressure was introduced. It was then
      followed by the open- and baby-lung concept in order to open up the lung and keep
      the lung open. However, these strategies are followed with several adverse
      effects. Therefore, studies were performed in order to improve the outcome of
      mechanical ventilation with less invasive strategy. This review aims to summarize
      recent concept of less invasive mechanical ventilation. 

PMID- 24448341
TI  - Current challenges in atomistic simulations of glasses for biomedical
      applications.
AB  - Atomic-scale computer simulations have emerged as a powerful tool to probe at a
      very high resolution the structural and dynamical properties of amorphous and
      crystalline biomaterials with a direct impact on their biological activity. In
      particular, bioactive glasses (BGs) represent a target of high strategic
      importance for the simulations, due to the central role that they play in the
      broad arena of materials for repairing and regenerating tissues. Simulations
      aimed at understanding the properties of bioactive glasses thus reveal the
      potential, and also the limitations, of computational approaches to support the
      rational development of biomaterials. This perspective article examines several
      key challenges that computer simulations of BGs are currently dealing with and
      that will need to be effectively tackled in order to achieve further substantial
      progress in this field. Relevant examples are the identification of new
      structural descriptors, the modelling of ion migration, and the simulation of
      nanosized samples, which are discussed in relation to the underlying issues, such
      as the limited space and time scales that can be probed in atomic-scale
      simulations. 

PMID- 24448342
TI  - A five-component nanorotor with speed regulation.
AB  - A five-component supramolecular nanorotor with reversibly acting brakes has been
      prepared from a four-component nanorotor by adding the photo- and heat-responsive
      2,2'-diazastilbene as a signal transducer. The rotational speed was reversibly
      switched between 86 and 38 kHz. 

PMID- 24448343
TI  - Increased prescription of antidepressants shows correction of inadequate duration
      of treatment of depression.

PMID- 24448344
TI  - Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis
      susceptibility gene.
AB  - OBJECTIVE: To evaluate the contribution of the SPP1 rs11439060 and rs9138
      polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid
      arthritis (RA) genetic background according to anti-citrullinated protein
      antibodies (ACPAs) status of RA individuals. METHODS: We analysed a total of
      11,715 RA cases and 26,493 controls from nine independent cohorts; all
      individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and
      rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on
      osteopontin (OPN) expression in macrophages and OPN serum levels was
      investigated. RESULTS: We provide evidence for a distinct contribution of SPP1 to
      RA susceptibility according to ACPA status: the combination of >=3 SPP1
      rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity
      (p=1.29*10(-5), ORACPA-negative 1.257 (1.135 to 1.394)) and less with ACPA
      positivity (p=0.0148, ORACPA-positive 1.072 (1.014 to 1.134)). The ORs between
      these subgroups (ie, ACPA-positive and ACPA-negative) significantly differed
      (p=7.33*10(-3)). Expression quantitative trait locus analysis revealed an
      association of the SPP1 risk-allele combination with decreased SPP1 expression in
      peripheral macrophages from 599 individuals. To corroborate these findings, we
      found an association of the SPP1 risk-allele combination and low serum level of
      secreted OPN (p=0.0157), as well as serum level of secreted OPN correlated
      positively with ACPA production (p=0.005; r=0.483). CONCLUSIONS: We demonstrate a
      significant contribution of the combination of SPP1 rs11439060 and rs9138
      frequent alleles to risk of RA, the magnitude of the association being greater in
      patients negative for ACPAs.

PMID- 24448345
TI  - Humoral immune response to vaccines in patients with rheumatoid arthritis treated
      with tocilizumab: results of a randomised controlled trial (VISARA).
AB  - OBJECTIVE: To evaluate the effect of tocilizumab (TCZ), an interleukin 6 receptor
      inhibitor, on humoral immune responses to immunisations in patients with
      rheumatoid arthritis (RA). METHODS: Patients with RA with inadequate
      response/intolerance to one or more anti-tumour necrosis factor-alpha agents were
      randomly assigned (2:1) to TCZ 8 mg/kg intravenously every 4 weeks plus
      methotrexate (MTX) or MTX alone up until week 8. Serum was collected before
      vaccination at week 3, antibody titres were evaluated at week 8, and then all
      patients received TCZ+MTX through week 20. End points included proportion of
      patients responding to >=6/12 pneumococcal polysaccharide vaccine (PPV23)
      serotypes (primary) and proportions responding to tetanus toxoid vaccine (TTV;
      secondary) at week 8. RESULTS: 91 patients were randomised. At week 8, 60.0% of
      TCZ+MTX and 70.8% of MTX patients responded to >=6/12 PPV23 serotypes, with
      insufficient evidence for any difference in treatments (10.8% (95% CI -33.7 to
      12.0)), and 42.0% and 39.1%, respectively, responded to TTV. Two of three TCZ+MTX
      patients with non-protective baseline TTV antibody titres achieved protective
      levels by week 8. The safety profile of TCZ was consistent with previous reports.
      CONCLUSIONS: Short-term TCZ treatment does not significantly attenuate humoral
      responses to PPV23 or TTV. To maximise vaccine response, patients should be up to
      date with immunisations before starting TCZ treatment. CLINICALTRIALSGOV
      IDENTIFIER: NCT01163747.

PMID- 24448346
TI  - Paying attention to arbitrary causality and the preciseness of conclusion.

PMID- 24448347
TI  - Inducible chondrocyte-specific overexpression of BMP2 in young mice results in
      severe aggravation of osteophyte formation in experimental OA without altering
      cartilage damage.
AB  - OBJECTIVES: In osteoarthritis (OA) chondrocytes surrounding lesions express
      elevated bone morphogenetic protein 2 (BMP2) levels. To investigate the
      functional consequence of chondrocyte-specific BMP2 expression, we made a
      collagen type II dependent, doxycycline (dox)-inducible BMP2 transgenic mouse and
      studied the effect of elevated BMP2 expression on healthy joints and joints with
      experimental OA. METHODS: We cloned a lentivirus with BMP2 controlled by a tet
      responsive element and transfected embryos of mice containing a collagen type II
      driven cre-recombinase and floxed rtTA to gain a mouse expressing BMP2 solely in
      chondrocytes and only upon dox exposure (Col2-rtTA-TRE-BMP2). Mice were treated
      with dox to induce elevated BMP2 expression. In addition, experimental OA was
      induced (destabilisation of the medial meniscus model) with or without dox
      supplementation and knee joints were isolated for histology. RESULTS: Dox
      treatment resulted in chondrocyte-specific upregulation of BMP2 and severely
      aggravated formation of osteophytes in experimental OA but not in control mice.
      Moreover, elevated BMP2 levels did not result in alterations in articular
      cartilage of young healthy mice, although BMP2-exposure did increase VDIPEN
      expression in the articular cartilage. Strikingly, despite apparent changes in
      knee joint morphology due to formation of large osteophytes there were no
      detectible differences in articular cartilage: none with regard to structural
      damage nor in Safranin O staining intensity when comparing destabilisation of the
      medial meniscus with or without dox exposure. CONCLUSIONS: Our data show that
      chondrocyte-specific elevation of BMP2 levels does not alter the course of
      cartilage damage in an OA model in young mice but results in severe aggravation
      of osteophyte formation.

PMID- 24448348
TI  - Levels of soluble osteoclast-associated receptor (sOSCAR) in rheumatoid
      arthritis: link to disease severity and cardiovascular risk.

PMID- 24448349
TI  - Vitamin D receptor regulates TGF-beta signalling in systemic sclerosis.
AB  - BACKGROUND: Vitamin D receptor (VDR) is a member of the nuclear receptor
      superfamily. Its ligand, 1,25-(OH)2D, is a metabolically active hormone derived
      from vitamin D3. The levels of vitamin D3 are decreased in patients with systemic
      sclerosis (SSc). Here, we aimed to analyse the role of VDR signalling in
      fibrosis. METHODS: VDR expression was analysed in SSc skin, experimental fibrosis
      and human fibroblasts. VDR signalling was modulated by siRNA and with the
      selective agonist paricalcitol. The effects of VDR on Smad signalling were
      analysed by reporter assays, target gene analyses and coimmunoprecipitation. The
      effects of paricalcitol were evaluated in the models of bleomycin-induced
      fibrosis and fibrosis induced by overexpression of a constitutively active
      transforming growth factor-beta (TGF-beta) receptor I (TBRI(CA)). RESULTS: VDR
      expression was decreased in fibroblasts of SSc patients and murine models of SSc
      in a TGF-beta-dependent manner. Knockdown of VDR enhanced the sensitivity of
      fibroblasts towards TGF-beta. In contrast, activation of VDR by paricalcitol
      reduced the stimulatory effects of TGF-beta on fibroblasts and inhibited collagen
      release and myofibroblast differentiation. Paricalcitol stimulated the formation
      of complexes between VDR and phosphorylated Smad3 in fibroblasts to inhibit Smad
      dependent transcription. Preventive and therapeutic treatment with paricalcitol
      exerted potent antifibrotic effects and ameliorated bleomycin- as well as
      TBRI(CA)-induced fibrosis. CONCLUSIONS: We characterise VDR as a negative
      regulator of TGF-beta/Smad signalling. Impaired VDR signalling with reduced
      expression of VDR and decreased levels of its ligand may thus contribute to
      hyperactive TGF-beta signalling and aberrant fibroblast activation in SSc.

PMID- 24448350
TI  - Probing electrons in TiO2 polaronic trap states by IR-absorption: evidence for
      the existence of hydrogenic states.
AB  - An important step in oxide photochemistry, the loading of electrons into shallow
      trap states, was studied using infrared (IR) spectroscopy on both, rutile TiO2
      powders and single-crystal, r-TiO2(110) oriented samples. After UV-irradiation or
      n-doping by exposure to H-atoms broad IR absorption lines are observed for the
      powders at around 940 cm(-1). For the single crystal substrates, the IR
      absorption bands arising from an excitation of the trapped electrons into higher
      lying final states show additional features not observed in previous work. On the
      basis of our new, high-resolution data and theoretical studies on the polaron
      binding energy in rutile we propose that the trap states correspond to polarons
      and are thus intrinsic in nature. We assign the final states probed by the IR
      experiments to hydrogenic states within the polaron potential. Implications of
      these observations for photochemistry on oxides will be briefly discussed.

PMID- 24448356
TI  - Transparent displays enabled by resonant nanoparticle scattering.
AB  - The ability to display graphics and texts on a transparent screen can enable many
      useful applications. Here we create a transparent display by projecting
      monochromatic images onto a transparent medium embedded with nanoparticles that
      selectively scatter light at the projected wavelength. We describe the optimal
      design of such nanoparticles, and experimentally demonstrate this concept with a
      blue-color transparent display made of silver nanoparticles in a polymer matrix.
      This approach has attractive features including simplicity, wide viewing angle,
      scalability to large sizes and low cost. 

PMID- 24448357
TI  - G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and
      promote carcinoma cell proliferation and migration.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is a pro-inflammatory
      cytokine that stimulates myeloid stem cell maturation, proliferation, and
      migration into circulation. Despite being a known growth factor, the impact of G
      CSF on solid tumours has not been well examined. G-CSF receptor (G-CSFR) is
      expressed by some tumours, and thus the aim of this study was to examine the
      expression and impact of G-CSF and G-CSFR on gastrointestinal tumours. METHODS:
      In this study, G-CSF expression was examined in human gastric and colon tumours
      and by tumour-derived stromal myofibroblasts and carcinoma cells. G-CSFR
      expression was examined on carcinoma cells isolated from human tissues. The
      effects of G-CSF on gastric and colon carcinoma cell proliferation, migration,
      and signalling were examined. RESULTS: G-CSFR was highly expressed in 90% of
      human gastric and colon carcinomas. G-CSF was also found to be highly produced by
      stromal myofibroblasts and carcinoma cells. Exposure of carcinoma cells to G-CSF
      led to increased proliferation and migration, and expansion of a sub-population
      of carcinoma cells expressing stem-like markers. These processes were dependent
      on ERK1/2 and RSK1 phosphorylation. CONCLUSIONS: These data suggest that the G
      CSF/R axis promotes gastric and colorectal cancer development and suggest they
      are potential tumour targets.

PMID- 24448358
TI  - Prognostic value of microRNA expression in operable non-small cell lung cancer
      patients.
AB  - BACKGROUND: About 50% of non-small cell lung cancer (NSCLC) patients develop
      distant metastases following pulmonary resection. Currently, there are no
      reliable factors allowing for individual selection of high-risk patients for
      adjuvant systemic therapies. METHODS: We assessed by quantitative reverse
      transcription PCR microRNA (miRNA) expression in 273 stage I-IIIA NSCLC samples.
      Expression of 677 miRNAs was evaluated in fresh-frozen tumour samples in the
      training cohort of 50 squamous cell carcinoma (SCC) patients who underwent
      curative surgery. Of those, 20 patients developed distant metastases, and 30 were
      free of recurrence for >4 years. In the second step, miRNAs with highest
      predictive value for distant relapse were re-evaluated in formalin-fixed paraffin
      embedded material in an independent group of 134 stage I-IIIA SCC patients.
      Additionally, the same miRNAs were investigated in 89 lung adenocarcinoma (AC)
      patients and in normal lung parenchyma (NLP). RESULTS: In the training cohort of
      SCC, six miRNAs were differently expressed in the non-recurrent vs recurrent
      groups and correlated with distant recurrence-free survival, however none reached
      the level of significance after correction for multiple testing. Of these six
      miRNAs, miR-662, -192 and -192* were confirmed as prognostic in the independent
      SCC cohort. Expression of miR-128, -10b, -502-3p and -192 differed between SCC
      and AC, and miR-128 and -192 - between NLP and NSCLC. CONCLUSIONS: We identified
      three new miRNAs predictive of distant relapse in operable SCC. Future miRNA
      studies should account for differences between NSCLC subtypes.

PMID- 24448359
TI  - Body mass index and circulating oestrone sulphate in women treated with adjuvant
      letrozole.
AB  - BACKGROUND: Obesity is an independent adverse prognostic factor in early breast
      cancer patients, but it is still controversial whether obesity may affect
      adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two
      clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate
      whether the circulating oestrogen levels during treatment with the aromatase
      inhibitor letrozole are related to body mass index (BMI) in postmenopausal women
      with breast cancer. METHODS: Plasma concentration of oestrone sulphate (ES) was
      evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after
      at least 6 weeks of letrozole therapy (steady-state time). Patients were divided
      into four groups according to BMI. Differences among the geometric means (by
      ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and
      BMI were assessed. RESULTS: Picomolar geometric mean values (95% confidence
      interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2,
      n=150) when BMI was <25.0 kg m(-2); 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m(
      2); 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m(-2); and 43.3 (23.0-81.7, n=16)
      when >=35.0 kg m(-2). No statistically significant difference in terms of ES
      levels among groups and no correlation with BMI were observed. CONCLUSIONS: Body
      mass index does not seem to affect circulating oestrogen levels in letrozole
      treated patients.

PMID- 24448360
TI  - Antitumour activity of the recombination polypeptide GST-NT21MP is mediated by
      inhibition of CXCR4 pathway in breast cancer.
AB  - BACKGROUND: CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived
      factor-1alpha (SDF-1alpha, also known as CXCL12) have important roles in
      promoting tumour growth and metastasis. Therefore, targeting CXCR4 could be a
      promising strategy for treatment of human cancer. METHODS: To achieve this goal,
      we developed a highly purified recombination polypeptide (GST-NT21MP), which is a
      synthetic 21-mer peptide antagonist of CXCR4 (NT21MP) derived from the viral
      macrophage inflammatory protein II by fermentation technology, affinity
      chromatography and fast protein liquid chromatography. In this study, we used
      multiple methods such as MTT assay, FACS, invasion assay, RT-PCR and western blot
      to explore the efficacy and mechanism by which GST-NT21MP inhibits cell growth,
      migration and invasion of breast cancer in vitro and in vivo. RESULTS: We found
      that blockade of CXCR4 pathway by GST-NT21MP decreased SDF-1-induced cell growth,
      adhesion and migration capacities in breast cancer cells. Moreover, GST-NT21MP
      significantly retarded pulmonary metastasis in vivo. Furthermore, GST-NT21MP
      mediated antitumour activity was found to be associated with reduced
      phosphorylated Src, Akt, FAK and ERK1/2 as well as decreased Bcl-2. CONCLUSIONS:
      Our results suggest that GST-NT21MP could be a potential anticancer agent for the
      treatment of breast cancer.

PMID- 24448361
TI  - Incidence of thyroid cancer in England by ethnic group, 2001-2007.
AB  - BACKGROUND: Thyroid cancer incidence is increasing worldwide, but with large
      variations in incidence that may reflect either diagnostic bias or true ethnic
      differences. We sought to determine the effect of ethnicity on the incidence of
      thyroid cancer in England, a multiethnic population with a single health-care
      system. METHODS: We analysed 11,263 thyroid cancer registrations with ethnicity
      obtained by linkage to the Hospital Episodes Statistics database. Incidence rate
      ratios (RRs) adjusted for age, sex and income were calculated for the six main
      non-White ethnic groups in England compared with Whites and to each other.
      RESULTS: Thyroid cancer incidence was higher in all ethnic groups, except
      Indians, compared with Whites: in Pakistanis (RR 1.79, 99% floating confidence
      interval (FCI) 1.47-2.19); Bangladeshis (RR 1.99, 99% FCI 1.46-2.71); Black
      Africans (RR 1.69, 99% FCI 1.34-2.13); Black Caribbeans (RR 1.56, 99% FCI 1.25
      1.93); and Chinese (RR 2.14, 99% FCI 1.63-2.80). CONCLUSION: The risk of thyroid
      cancer in England varies significantly by ethnicity. The elevated incidence in
      most ethnic minorities is unlikely to be due to diagnostic bias and warrants
      further investigation.

PMID- 24448362
TI  - Comment on 'External multicentre validation of a nomogram predicting the risk of
      relapse in patients with borderline ovarian tumours'.

PMID- 24448363
TI  - Distribution of breast cancer risk from SNPs and classical risk factors in women
      of routine screening age in the UK.

PMID- 24448364
TI  - Thrombosis in ovarian cancer: a case control study.
AB  - BACKGROUND: Thrombotic events are common in cancer patients and have been
      associated with an adverse prognosis in large registry-based studies. METHODS: A
      retrospective cohort of 417 patients with ovarian cancer treated at a tertiary
      cancer centre between 2006 and 2009 was studied to identify the incidence and
      risk factors for thrombotic events and the prognostic impact of thrombosis.
      Patient outcomes were evaluated against a matched control group without
      thrombosis. RESULTS: Ninety-nine thrombotic events occurred in 90 patients
      (21.6%) from 8 months before diagnosis to 56 months following diagnosis, peaking
      in the 4 months following diagnosis. Patients with thrombosis were older (mean 65
      vs 61 years, P=0.007), had a worse performance status (PS >=2: 29.9% vs 9.5%,
      P<0.0001) and had a more advanced FIGO stage (FIGO III/IV 75.6% vs 56.9%,
      P<0.0001) than patients without thrombosis. Shorter overall survival was seen in
      patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis than
      without thrombosis (P=0.001). When the control group was matched for stage and
      PS, no survival difference was seen (P=0.91). CONCLUSION: Ovarian cancer patients
      with thrombotic events had a shorter survival. However, when matched for
      prognostic factors (PS and FIGO stage), thrombosis did not impact upon prognosis.

PMID- 24448366
TI  - Silicone passive equilibrium samplers as 'chemometers' in eels and sediments of a
      Swedish lake.
AB  - Passive equilibrium samplers deployed in two or more media of a system and
      allowed to come to equilibrium can be viewed as 'chemometers' that reflect the
      difference in chemical activities of contaminants between the media. We applied
      silicone-based equilibrium samplers to measure relative chemical activities of
      seven 'indicator' polychlorinated biphenyls (PCBs) and hexachlorobenzene in eels
      and sediments from a Swedish lake. Chemical concentrations in eels and sediments
      were also measured using exhaustive extraction methods. Lipid-normalized
      concentrations in eels were higher than organic carbon-normalized concentrations
      in sediments, with biota-sediment accumulation factors (BSAFs) of five PCBs
      ranging from 2.7 to 12.7. In contrast, chemical activities of the same pollutants
      inferred by passive sampling were 3.5 to 31.3 times lower in eels than in
      sediments. The apparent contradiction between BSAFs and activity ratios is
      consistent with the sorptive capacity of lipids exceeding that of sediment
      organic carbon from this ecosystem by up to 50-fold. Factors that may contribute
      to the elevated activity in sediments are discussed, including slower response of
      sediments than water to reduced emissions, sediment diagenesis and sorption to
      phytoplankton. The 'chemometer' approach has the potential to become a powerful
      tool to study the thermodynamic controls on persistent organic chemicals in the
      environment and should be extended to other environmental compartments. 

PMID- 24448365
TI  - Influence of pre-diagnostic cigarette smoking on colorectal cancer survival:
      overall and by tumour molecular phenotype.
AB  - BACKGROUND: Smoking is a risk factor for incident colorectal cancer (CRC);
      however, it is unclear about its influence on survival after CRC diagnosis.
      METHODS: A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland
      and Labrador, Canada, was followed for mortality and recurrence until April 2010.
      Smoking and other relevant data were collected by questionnaire after cancer
      diagnosis, using a referent period of '2 years before diagnosis' to capture pre
      diagnosis information. Molecular analyses of microsatellite instability (MSI)
      status and BRAF V600E mutation status were performed in tumour tissue using
      standard techniques. Multivariate hazard ratios (HRs) and 95% confidence
      intervals (CIs) were calculated with Cox proportional hazards regression,
      controlling for major prognostic factors. RESULTS: Compared with never smokers,
      all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95%
      CI: 1.04-3.06), but not for former (HR: 1.06; 95% CI: 0.71-1.59) smokers. The
      associations of cigarette smoking with the study outcomes were higher among
      patients with >=40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03-2.85;
      disease-free survival (DFS: HR: 1.99; 95% CI: 1.25-3.19), those who smoked >=30
      cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22-2.67), and those with
      microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04-1.82
      and DFS: HR: 1.32; 95% CI: 1.01-1.72). Potential heterogeneity was noted for sex
      (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at
      diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged >=60: P
      for heterogeneity=0.03). CONCLUSIONS: Pre-diagnosis cigarette smoking is
      associated with worsened prognosis among patients with CRC.

PMID- 24448367
TI  - Streptavidin binding as a model to characterize thiol-ene chemistry-based
      polyamine surfaces for reversible photonic protein biosensing.
AB  - Biotin- and iminobiotin-bonded surfaces obtained by thiol-ene chemistry and
      subsequent modification with polyamines were characterized with respect to
      streptavidin-binding capacity and reversibility for photonic biosensing using X
      ray photoelectron spectroscopy and Mach-Zehnder-interferometric sensors. The
      streptavidin-iminobiotin system was exploited for reversible multilayer
      deposition and determination of affinity constants on each layer. 

PMID- 24448369
TI  - Electrophysiological variability in the SH-SY5Y cellular line.
AB  - The basic electrophysiological properties of SH-SY5Y tumour cells have been
      studied by whole cell patch-clamp in voltage clamp configuration. The results
      shown the existence of a large variability of the response among individual cells
      in the same experimental conditions. Experiments conducted by using different
      ionic concentrations of the recording pipette filling solution, yielded a
      significant variability of peak current amplitude for all the filling solutions
      used. In addition, variability among groups was detected. The inter-group
      variability was not dependent on the different ionic components among the groups.
      Our results confirm earlier findings that this cell line is not constituted of an
      uniform population of cells. Moreover, from the present results we can conclude
      that these cells have diverse regulatory patterns of membrane conductance,
      probably due to both the expression as well as a non precise regulation of the
      membrane density of the different channels. 

PMID- 24448368
TI  - Triptolide induces apoptosis through the SERCA 3 upregulation in PC12 cells.
AB  - Diterpenoid triepoxide - Triptolide (TTL) - increased protein levels of the
      noradrenaline transporter in three pheochromocytoma cell lines. This transporter
      is involved in the apoptosis induction through the inhibition of a transcription
      factor NF-kappa B. Nevertheless, calcium release from the endoplasmic reticulum
      can also induce inner mitochondrial pathway of apoptosis in variety of cells.
      Therefore, the aim of this work was to evaluate an involvement of calcium and,
      more specifically, the intracellular calcium transport systems in the apoptosis
      induction in pheochrocytoma cell line PC12. We observed significantly increased
      amount of reticular calcium in TTL-treated cells compared to control, untreated
      cells. Surprisingly, gene expression of the IP3 receptors was not changed after
      the TTL treatment, but ryanodine receptor of the type 2 (RyR2) was downregulated
      and sarco/endoplasmic reticulum calcium ATPase type 3 (SERCA 3) was upregulated
      in TTL- treated cells, compared to untreated controls. SERCA 3 blocking with the
      specific blocker thapsigargin prevented increase in apoptosis observed by the TTL
      treatment. Decrease in the ATP production by a replacement of glucose in the
      cultivation medium for its nonutilizable analog 2-deoxyglucose also prevented
      induction of the apoptosis in TTL-treated PC12 cells. Thus, these results suggest
      that upregulation of the SERCA 3 is ultimately involved in the TTL-induced
      apoptosis in PC12 cells. 

PMID- 24448370
TI  - The effects of acute intermittent hypoxia on cardiovascular parameters in
      normotensive and chronic hypobaric hypoxia-induced hypertensive rabbits.
AB  - The effects of both chronic hypoxia and acute intermittent hypoxia (AIH) on
      cardiovascular system are unclear. We designed this study to develop a rabbit
      model of hypertension by exposure to chronic hypobaric hypoxia (CHH) and to
      investigate the effects of AIH on hypertensive rabbits. Present study was
      performed in 13 albino rabbits that divided into CHH and control groups. To
      develop hypertension, the rabbits were placed in a hypobaric chamber (390 mmHg;
      22 hours/day, 30 days). Afterwards, AIH protocol was applied (8% FIO2 (Fraction
      of Inspired Oxygen) 1 min + 5 min normoxia, 20 cycles, 2 hours) to rabbits
      anesthetized with urethane and alpha-chloralose. Mean arterial pressure (MAP),
      heart rate (HR) and hematocrit values have been determined. Also asymmetric
      dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1
      and norepinephrine values have been analyzed in blood. We developed a model of
      hypertension in rabbits via exposure to severe CHH and we believe that ADMA is an
      important parameter in the development and permanence of CHH-induced
      hypertension. The main finding of this sudy was the depressor effect of AIH on
      blood pressure and heart rate in CHH- induced hypertension model. Finally, we
      believe that AIH protocol may be applicable for prevention and treatment of
      hypertension if properly developed. 

PMID- 24448371
TI  - Antimanic drug sensitizes breast cancer cell line to ionizing radiation.
AB  - Breast cancer is one of the most prevalent types of cancer among women. Lithium
      chloride (LiCl) is an FDA-approved drug for bipolar disorder. Breast cancer is
      reported to occur with higher rate in women with bipolar disorder. The effect of
      LiCl on the response of breast cancer cells to ionizing radiation has not been
      studied. We studied the effect of LiCl on the radiosensitivity of radioresistant
      T47D breast cancer cell line. Treatment of T47D cells with 20 mM LiCl for 24
      hours decreased the radioresistance of these cells indicated by clonogenic
      survival assay. Comet assay demonstrated decreased DNA repair in LiCl-treated
      cells. LiCl treatment also decreased the meiotic recombination 11 (Mre11) mRNA
      level. Mre11 is an essential protein for DNA repair whose transcription is
      regulated by beta-catenin protein. Western blot analysis indicated that the beta
      catenin protein level was decreased in LiCl-treated cells. LiCl increased
      glycogen synthase kinase-3beta (GSK-3beta) protein that is involved in beta
      catenin degradation. The results demonstrated that LiCl could radiosensitize T47D
      cells by decreasing DNA repair, partially through Mre11 repression. GSK
      3beta/beta-catenin/Mre11 pathway might be the connection between LiCl treatment
      and the decreased DNA repair in T47D cells.

PMID- 24448372
TI  - Potent cough suppression by physiologically active substance in human plasma.
AB  - Human plasma contains wide variety of bioactive proteins that have proved
      essential in therapeutic discovery. However many human plasma proteins remain
      orphans with unknown biological functions. Evidences suggest that some plasma
      components target the respiratory system. In the present study we adapted heparin
      affinity chromatography to fractionate human plasma for functional bioassay.
      Fractions from pooled human plasma yielded particular plasma fractions with
      strong cough suppressing effects. Purification yielded a fraction that was
      finally identified as an activated blood coagulation factor fXIa using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser
      desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS). The
      fraction almost completely suppressed coughs induced by either chemical or
      mechanical stimulation applied to larynx or bifurcation of guinea-pig trachea.
      Cough suppressing effect of the fraction and commercially available fXIa were one
      million times stronger than codeine and codeine only partially suppressed the
      mechanically triggered coughing in animal model. Recent reviews highlighted
      prominent shortcomings of current available antitussives, including narcotic
      opioids such as codeine and their unpleasant or intolerable side effects.
      Therefore, safer and more effective cough suppressants would be welcome, and
      present findings indicate that fXIa in human plasma as a very promising, new
      therapeutic candidate for effective antitussive action. 

PMID- 24448373
TI  - Association of specific diplotypes defined by common rs1800682 and rare
      rs34995925 single nucleotide polymorphisms within the STAT1 transcription binding
      site of the FAS gene promoter with preeclampsia.
AB  - The tolerance of fetal antigens by intradecidual T-cell involving the Fas
      mediated apoptosis plays an important role in the physiological course of
      pregnancy. Objective of this study is to determine the association of diplotypes
      of common rs1800682G and rare rs34995925C alleles within the STAT1 transcription
      binding site of the FAS promoter region with preeclampsia. There were 116
      preeclamptic women and 123 healthy control subjects from Hungary and Slovakia
      enrolled in the study. The presence of the GG or GA genotypes on rs1800682 was
      confirmed in 91 patients and 85 controls (OR = 1.628, 95%CI 0.907-2.92). The rare
      rs34995925 C allele laying 7 bp further from rs1800682 within STAT1 transcription
      binding site was detected in 3 preeclamptic cases and none healthy subjects.
      Haplotypes GT and AC were defined by common rs1800682G and rare rs34995925C
      alleles, respectively, and were considered as "low" FAS-producing. The
      combinations of GT or AC with normal FAS-producing haplotypes AT were considered
      as "low" FAS-producing diplotypes in dominant model. The "low" FAS -producing
      diplotype group of GT/GT, GT/AT, and AC/AT compared to the normal FAS-producing
      diplotype group of AT/AT showed OR = 1.91 (95%CI 1.04-3.48) and p = 0.03 for the
      association with preeclampsia.

PMID- 24448374
TI  - Long-term effects of somatostatin 14 on the pituitary-ovarian axis in rats.
AB  - The long-term effects of somatostatin 14 (SST-14) on the pituitary-ovarian axis
      were examined. Female Wistar rats received 20 ug/100g b.w. doses subcutaneously
      twice daily for 5 consecutive days in the infantile (from 11th to 15th day) or
      peripubertal (from 33rd to 37th day) period of life. Females treated as infants
      were killed in the peripubertal (38th day) or adult period of life (80th day),
      and those treated during peripuberty as adults (80th day). Pituitary follicle
      stimulating (FSH), luteinizing (LH) and somatotropic (GH) cells, and ovaries were
      analyzed by stereology and morphometry. Serum FSH and LH concentrations were
      determined by RIA. FSH and LH cell volumes were significantly decreased in
      pituitaries of peripubertal females treated with SST-14 as infants, and in adult
      females treated during peripuberty. GH cell volume was decreased in all treated
      rats. In the ovaries, enlargement of the non-growing pool of follicles was
      detected in adult females treated during peripuberty. SST-14 applied to infant
      rats did not lead to changes in initial follicular recruitment, but it disturbed
      follicle growth and development at later stages. It can be concluded that SST-14
      exerted long-term inhibitory effects on the pituitary-ovarian axis and GH cells
      in rats. 

PMID- 24448375
TI  - ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937
      cells.
AB  - This study was to investigate the cell killing effect of chlorin-e6 (Ce6)
      mediated sonodynamic therapy (SDT) on human leukemia U937 cells and explore the
      role of ERK signal pathway in the process. The ultrastructure changes of U937
      cells induced by ultrasonic irradiation were evaluated by scanning electron
      microscope (SEM) and transmission electron microscope (TEM). The viability of
      cells was evaluated by viacount assay. Apoptosis was analyzed using flow
      cytometer as well as fluorescence microscopy with 4'-6-diamidino-2-phenylindole
      (DAPI) staining. Western blotting was used to analyze the expression of mitogen
      activated protein kinase (MAPK). Intracellular reactive oxygen species (ROS) and
      mitochondria membrane potential (MMP) levels were also analyzed by flow cytometer
      after exposure. Our experiments showed that several distinct sonochemical effects
      were found after Ce6-mediated SDT treatment. Western blotting analysis indicated
      that the MAPK were activated. Especially, pre-treatment with ERK inhibitor U0126
      could additionally enhance SDT-induced cell viability loss, early- and late
      apoptotic rate, chromatin condensation, DNA fragmentation and caspase-3
      activation. Besides, a mass of ROS accumulation and a conspicuous loss of
      mitochondrial membrane potential were detected in U937 cells. These findings
      suggested ERK signal pathway may deliver a survival signal which counteracts SDT
      induced cell death, while combination with U0126 could significantly potentiate
      the SDT-induced cytotoxic effect in U937 cells. 

PMID- 24448376
TI  - The risk of asthma in rheumatoid arthritis: a population-based cohort study.
AB  - BACKGROUND: Several studies discussed the relations between asthma and rheumatoid
      arthritis (RA) but the results were controversial. These studies were either
      questionnaire based or with small study populations. We aimed to examine the risk
      of asthma among RA patients in a nationwide population. METHODS: We conducted a
      cohort study using data from the National Health Insurance system of Taiwan. The
      RA cohort included 27 602 patients who were newly diagnosed and recruited between
      1998 and 2008. Each patient was randomly frequency-matched with three people
      without RA on age group, sex and the year of index date from the general
      population. The occurrence of asthma was followed up until the end of 2010. The
      relative risks of asthma were estimated using Cox proportional hazard models
      after adjusting for age and comorbidities. RESULT: The overall incidence rate of
      asthma was 2.07-fold greater in the RA cohort than in the non-RA cohort (4.56 vs.
      2.22 per 1000 person-years, 95% CI = 1.99-2.15). Stratified analyses by gender,
      age group and comorbidity revealed that the risk of asthma associated with RA was
      higher in females (adjusted hazard ratio (HR) = 2.18, 95% CI = 1.97-2.41),
      individuals younger than 40 years old (adjusted HR = 3.26, 95% CI = 2.09-5.11)
      and without comorbidity (adjusted HR = 2.17, 95% CI = 1.97-2.39). CONCLUSION:
      Patients with RA had a significantly higher risk of developing asthma than
      healthy people in all sex and age subgroups. Stratified analyses indicated that
      there was a higher risk in women with RA than in men with RA when compared to
      their counterpart. Similarly, the HR of asthma associated with RA was higher in
      younger subjects, although the incidence rate increased with age.

PMID- 24448377
TI  - Tuberculous muscle abscess.

PMID- 24448378
TI  - Aggressive gyriform calcifications and seizures after ischemia stroke in a
      patient with primary hyperparathyroidism.

PMID- 24448379
TI  - A young woman with pancreatitis and odynophagia.

PMID- 24448380
TI  - High prevalence and risk factors for kidney dysfunction in patients with
      atherosclerotic cardio-cerebrovascular disease.
AB  - BACKGROUND: Patients with atherosclerotic cardio-cerebrovascular disease are at
      high risk of kidney dysfunction because of the overlap of several risk factors.
      The purpose of this study is to examine the prevalence and characteristics and
      risk factors for kidney dysfunction in the cardio-cerebrovascular disease
      population. METHODS: Renal functions of 1012 patients with the cardio
      cerebrovascular disease were evaluated with the purpose of evaluating
      characteristics of the incidence, risk factors for kidney dysfunction in the
      cardio-cerebrovascular disease population. RESULTS: In the univariate analysis,
      the major risk factors for kidney dysfunction in the patients with the cardio
      cerebrovascular disease were age, gender, hypertension, diabetes mellitus,
      dyslipidemia and serum uric acid. In the patients with both hypertension and
      diabetes mellitus the percentages of significantly decreased eGFR were 25.6%.
      Results of multivariable analysis showed that diabetes mellitus (odds ratio (OR)
      1.609, 95% confidence intervals (CI) 1.08-2.398, P = 0.019), hypertension (OR
      1.547, 95% CI 1.049-2.281, P = 0.028) and serum uric acid (OR 1.009, 95% CI 1.007
      1.010, P < 0.001) were independent risk factors for reduced kidney function.
      CONCLUSIONS: In the context of the cardio-cerebrovascular disease kidney
      dysfunction is common and has a high prevalence. Patients with both cardio
      cerebrovascular disease and kidney dysfunction at any stage should be recognized
      as high-risk population.

PMID- 24448381
TI  - The rapid access chest pain clinic: unmet distress and disability.
AB  - AIMS: To determine the characteristics, clinical needs and level of health-care
      use of patients with non-cardiac (NCCP) and cardiac-chest pain (CCP) attending a
      Rapid Access Chest Pain Clinic in an inner-London Hospital. METHODS: A cross
      sectional comparison of NCCP and CCP patients on measures of pain, mood, beliefs,
      somatic symptoms and use of services completed by patients attending the Rapid
      Access Chest Pain Clinic over an 18-month period. RESULTS: There were no
      significant differences between NCCP and CCP patients in terms of chest pain
      frequency, duration or severity or associated distress; however, NCCP were
      younger (53 vs. 60, OR = 1.05) and reported 'atypical' pain more frequently (82%
      vs. 50%, OR = 3.72). The NCCP group reported more panic-type beliefs about chest
      pain (5.8 vs. 4.3, P < 0.05) and lower 'illness coherence' (a patient's belief
      that the illness 'makes sense') (3.5 vs. 4.7, P < 0.05). Anxiety and depression
      scores were similar in both groups. Both groups had similar levels of health-care
      use but patients with NCCP saw more types of health-care worker (mean 1.7) than
      those with CCP (mean 1.4, P < 0.05). CONCLUSION: Patients with NCCP are as
      disabled and distressed as patients with CCP however current services fail to
      meet their needs. We suggest that a biopsychosocial approach should be explored.

PMID- 24448382
TI  - Reply to: analgesic efficacy of ultrasound-guided adductor canal blockade after
      arthroscopic anterior cruciate ligament reconstruction.

PMID- 24448383
TI  - Making room for qualitatively-driven mixed-method research.

PMID- 24448386
TI  - A nanocomposite superstructure of metal oxides with effective charge transfer
      interfaces.
AB  - The alignment of nanoparticle building blocks into ordered superstructures is one
      of the key topics in modern colloid and material chemistry. Metal oxide
      mesocrystals are superstructures of assembled nanoparticles of metal oxides and
      have potentially tunable electronic, optical and magnetic properties, which would
      be useful for applications ranging from catalysis to optoelectronics. Here we
      report a facile and general approach for synthesizing metal oxide mesocrystals
      and developing them into new nanocomposite materials containing two different
      metals. The surface and internal structures of the mesocrystals were fully
      characterized by electron microscopy techniques. Single-particle confocal
      fluorescence spectroscopy, electron paramagnetic resonance spectroscopy and time
      resolved diffuse reflectance spectroscopy measurements revealed that efficient
      charge transfer occurred between n-type and p-type semiconductor nanoparticles in
      the composite mesocrystals. This behaviour is desirable for their applications
      ranging from catalysis, optoelectronics and sensing, to energy storage and
      conversion. 

PMID- 24448385
TI  - MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through
      suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines.
AB  - Overexpression of DNA methyltransferase 1 (DNMT-1) is observed mostly in
      pancreatic cancer and it can cause tumor suppressor genes silencing in this
      disease. Recent studies suggest that abnormal expressions of microRNAs (miRs) are
      involved in pathogenesis of different types of human cancers including pancreatic
      cancer. In this study we aimed to investigate the effect of miR-148b and -152 on
      reverting the tumorigenic phenotype of pancreatic cancer cell lines. In order to
      investigate whether miR-148b and -152 are involved in the regulation of DNMT-1,
      luciferase reporter assay was used and confirmed that the DNMT-1 mRNA could be a
      target for miR-148b and miR-152. Furthermore, overexpression of miR-148b and -152
      in pancreatic cancer cell lines (MIA PaCa-2 and AsPC-1) decreased DNMT-1
      expression (53% and 59% respectively), returned DNA methylation to normal
      patterns and induced re-expression of tumor suppressor genes, like BNIP3 (4.7-
      and 3.8-fold) and SPARC (5.3- and 2.9-fold) for miR-148b and -152 respectively.
      Moreover, the introduced miR-148b and -152 could inhibit the proliferation of MIA
      PaCa-2 (35% and 37% respectively) and AsPC-1 (39% and 40% respectively) cell
      lines. The apoptosis rates of MIA PaCa-1 after treatment with miR-148b and -152
      were 10% and 8% respectively; while these rates in AsPC-1 were 16% and 11%
      respectively. Conclusively these findings mean that miRs that are targeting DNMT
      1 and modifying methylation status of tumor suppressor genes such as BNIP3 and
      SPARC can be applied in killing the pancreatic cancer cells and decreasing the
      tumorigenicity of these cells.

PMID- 24448387
TI  - 9-Hydroxypheophorbide alpha-mediated photodynamic therapy induces matrix
      metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in Hep-2 cells via ROS
      mediated suppression of the ERK pathway.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a promising treatment modality for
      malignant diseases through the generation of reactive oxygen species (ROS). In
      this study, we assessed the change of migration and invasion of HEp-2 cells after
      sublethal doses of 9-hydroxypheophorbide alpha (9-HPbD)-mediated PDT in vitro,
      and explored the role of ROS in 9-HPbD-PDT-induced anti-metastatic effects in HEp
      2 cells. METHODS: Following PDT, ROS were measured by a fluorescence microscope
      in both the presence and absence of glutathione (GSH) pretreatment. Wound healing
      assay, cell migration assay, and matrigel invasion assay were used to evaluate
      the cellular migration and invasion. Western blot was performed to investigate
      the signaling pathways that may have been involved. RESULTS: ROS were rapidly
      generated in 9-HPbD-loaded HEp-2 laryngeal cancer cells by the activation of a
      diode laser and were significantly inhibited by a 6-h GSH pretreatment. Wound
      healing assay, cell migration assay, and matrigel invasion assay showed that
      sublethal PDT significantly suppressed the migration and invasion of HEp-2 cells.
      GSH decreased the ability of PDT to inhibit the invasion of HEp-2 cells. Western
      blot analysis showed that PDT significantly inhibited the phosphorylation of
      MEK1/2 and ERK1/2, and significantly suppressed the expression of MMP-2 and MMP-9
      after 24h following the implementation of sublethal PDT, and these efficacies of
      PDT could be abrogated by GSH pretreatment. CONCLUSIONS: 9-HPbD-PDT attenuated
      the migration and invasion of HEp-2 cells in vitro, which may be related to the
      down-regulated expression of MMP-2 and MMP-9 via ROS-mediated-inhibition of
      phosphorylation in the ERK/MEK signaling pathway.

PMID- 24448388
TI  - A prophet to modern medicine: Ernest Amory Codman's crucial contribution to the
      safety of anaesthetic practice.

PMID- 24448389
TI  - Direct access to isoindolines through tandem Rh(III)-catalyzed alkenylation and
      cyclization of N-benzyltriflamides.
AB  - The rhodium-catalyzed oxidative alkenylation of N-benzyltriflamides with olefins
      followed by an intramolecular cyclization via C-H bond activation is described.
      This method results in the direct and efficient synthesis of highly substituted
      isoindoline frameworks. 

PMID- 24448390
TI  - Synthesis of a SiO2/TiO2 hybrid boronate affinity monolithic column for specific
      capture of glycoproteins under neutral conditions.
AB  - A unique boronate-functionalized SiO2/TiO2 hybrid monolithic column was
      synthesized by a facile approach. Although a conventional boronic acid, 4
      vinylphenylboronic acid, was used as the affinity ligand, the prepared monolithic
      column exhibited specific capacity to capture glycoproteins including antibodies
      in aqueous solution at neutral pH. With the incorporation of titania, the
      monolith was highly hydrophilic, and the procedure of affinity chromatography
      could be performed under aqueous organic-solvent-free conditions. 

PMID- 24448391
TI  - N-methylpyridinium, a degradation product of trigonelline upon coffee roasting,
      stimulates respiratory activity and promotes glucose utilization in HepG2 cells.
AB  - N-Methylpyridinium (NMP) is a thermal degradation product of trigonelline formed
      upon coffee roasting and hypothesized to exert several health benefits in humans.
      Since for trigonelline evidence for hypoglycemic effects exists, we examined
      whether NMP also affects mechanisms of glucose utilization and cellular energy
      formation. For this purpose, the impact of trigonelline and NMP on respiratory
      activity, extracellular acidification, cellular adenosine nucleotides, energy
      supply from fatty acids and glucose as well as thermogenesis in HepG2 cells was
      analyzed. A 24 hour incubation with nanomolar concentrations of NMP enhanced
      oxygen consumption rates, resulting in increased ATP levels. Glucose was
      identified as the prevalent energy substrate as its uptake was augmented up to
      18.1% +/- 7.44% by NMP at 0.09 MUM, whereas the uptake of fatty acids decreased
      upon NMP treatment. Cellular glucose uptake was also stimulated by trigonelline
      administration; however, a shift to the anaerobic energy production pathway was
      monitored. Both pyridine derivatives induced thermogenesis, although trigonelline
      presumably promoted proton leaks, while NMP increased the concentration of the
      uncoupling protein-2. We provide evidence that both compounds appear to stimulate
      cellular energy metabolism in HepG2 cells. Human intervention studies are
      warranted to ensure these effects in vivo. 

PMID- 24448392
TI  - Tumour-infiltrating lymphocytes in the risk stratification of squamous cell
      carcinoma of the head and neck.

PMID- 24448395
TI  - GATA2 as a potential metastasis-driving gene in prostate cancer.
AB  - Effective treatment for metastatic prostate cancer is critically needed. The
      present study was aimed at identifying metastasis-driving genes as potential
      targets for therapy (oncotargets). A differential gene expression profile of
      metastatic LTL-313H and non-metastatic LTL-313B prostate cancer tissue
      xenografts, derived from one patient's specimen, was subjected to integrative
      analysis using the Ingenuity Upstream Regulator Analysis tool. Six candidate
      master regulatory genes were identified, including GATA2, a gene encoding a
      pioneer factor, a special transcription factor facilitating the recruitment of
      additional transcription factors. Elevated GATA2 expression in metastatic
      prostate cancer tissues correlated with poor patient prognosis. Furthermore,
      GATA2 gene silencing in human prostate cancer LNCaP cells led to a marked
      reduction in cell migration, tissue invasion, focal adhesion disassembly and to a
      dramatic change in cell transcriptomes, indicating that GATA2 plays a critical
      role in prostate cancer metastasis. As such, GATA2 could represent a prostate
      cancer metastasis-driving gene and a potential target for therapy of metastatic
      prostate cancer. 

PMID- 24448396
TI  - Variation in P450 oxidoreductase (POR) A503V and flavin-containing monooxygenase
      (FMO)-3 E158K is associated with minor alterations in nicotine metabolism, but
      does not alter cigarette consumption.
AB  - The rates of nicotine metabolism differ widely, even after controlling for
      genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Genetic
      variants in an additional nicotine-metabolizing enzyme, flavin-containing
      monooxygenase (FMO)-3, and an obligate microsomal CYP-supportive enzyme,
      cytochrome P450 oxidoreductase (POR), were investigated. We examined the impact
      of FMO3 E158K and POR A503V before and after stratifying by CYP2A6 metabolism
      group. In 130 nonsmokers of African descent who received 4 mg oral nicotine, FMO3
      158K trended toward slower nicotine metabolism in reduced CYP2A6 metabolizers
      (P=0.07) only, whereas POR 503V was associated with faster CYP2A6 activity
      (nicotine metabolite ratio) in normal (P=0.03), but not reduced, CYP2A6
      metabolizers. Neither FMO3 158K nor POR 503V significantly altered the nicotine
      metabolic ratio (N=659), cigarette consumption (N=667), or urine total nicotine
      equivalents (N=418) in smokers of African descent. Thus, FMO3 E158K and POR A503V
      are minor sources of nicotine metabolism variation, insufficient to appreciably
      alter smoking. 

PMID- 24448397
TI  - Improved performance and stability of field-effect transistors with polymeric
      residue-free graphene channel transferred by gold layer.
AB  - One of the most significant issues that occurs when applying chemical-vapor
      deposited (CVD) graphene (Gr) to various high-performance device applications is
      the result of polymeric residues. Polymeric residues remain on the Gr surface
      during Gr polymer support transfer to an arbitrary substrate, and these residues
      degrade CVD Gr electrical properties. In this paper, we propose that a thin layer
      of gold be used as a CVD Gr transfer layer, instead of a polymer support layer,
      to enable a polymer residue-free transfer. Comparative investigation of the
      surface morphological and qualitative analysis of residues on Gr surfaces and Gr
      field-effect transistors (GFETs) using two transfer methods demonstrates that
      gold-transferred Gr, with uniform, smooth, and clean surfaces, enable GFETs to
      perform better than Gr transferred by the polymer, polymethylmethacrylate (PMMA).
      In GFETs fabricated by the gold transfer method, field-effect carrier mobility
      was greatly enhanced and the position of the Dirac point was significantly
      reduced compared to GFETs fabricated by the PMMA transfer method. In addition,
      compared to the PMMA-transferred GFETs, the gold-transferred GFETs showed greatly
      increased stability with smaller hysteresis and higher resistance to gate bias
      stress effects. These results suggest that the gold transfer method for Gr
      provides significant improvements in GFET performance and reliability by
      minimizing the polymeric residues and defects on Gr. 

PMID- 24448398
TI  - Magical manoeuvre: a 5-s instructor's intervention helps lightweight female
      rescuers achieve the required chest compression depth.
AB  - BACKGROUND: Adequate chest compression (CC) depth is crucial for resuscitation
      outcomes. Lightweight rescuers, particularly women, are often unable to achieve
      the required 5-6 cm CC depth. This nonrandomized cohort study investigated new
      strategies to improve CC performance. OBJECTIVE: To evaluate the effects of a 5-s
      instructor's intervention on the depth of CCs performed by female rescuers during
      standard video self-instruction basic life support training. METHODS: Data were
      prospectively collected from January 2011 to January 2012 from 336 female medical
      and pharmacy students undergoing cardiopulmonary resuscitation (CPR) training at
      the Lithuanian University of Health Sciences. During the training process, the
      instructors performed a simple 5-s intervention (Andrew's manoeuvre) with all of
      the rescuers in the study group. The instructor pushed 10 times on the shoulders
      of each trainee while she performed CCs to achieve the maximal required
      compression depth. Immediately after training, the participants were asked to
      perform a 6-min basic life support test on a manikin that was connected to a PC
      with Skill Reporter System software; the quality of the participants' CPR skills
      was then evaluated. RESULTS: The CC depth in the study group increased by 6.4 mm
      (P<0.001) compared with the control group (52.9 vs. 46.6 mm). A regression
      analysis showed that Andrew's manoeuvre increased the depth of the CCs among
      women by 14.87*(1-0.01*weight) mm. CONCLUSION: A simple 5-s instructor's
      intervention during the CPR training significantly improved the performance of
      the female rescuers and helped them achieve the CC depth required by 2010
      resuscitation guidelines. Andrew's manoeuvre is most effective among the women
      with the lowest body weight.

PMID- 24448399
TI  - Laying the groundwork for proteomics: mass spectrometry from 1958 to 1988.
AB  - The development of mass spectrometric methods in peptide and protein chemistry in
      the author's laboratory is reviewed, from the first determination of the amino
      acid sequence of small peptides in the late 1950s to its use for the
      determination of the primary structure of large proteins by a combination of mass
      spectrometry and DNA sequencing in the late 1980s. This article is part of a
      Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini.
      Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and
      Jean-Charles Sanchez. 

PMID- 24448400
TI  - An integrated immunoproteomics and bioinformatics approach for the analysis of
      Schistosoma japonicum tegument proteins.
AB  - Schistosomiasis remains one of the major neglected tropical diseases (NTDs)
      causing morbidity of humans residing in the tropical countries. Much effort has
      been devoted to the development of vaccines, since it is recognized that vaccines
      can be served as an important supplementary component alongside chemotherapy for
      the future control and elimination of schistosomiasis. To accelerate digging new
      potential target antigens, it is essential to extensively and intensively search
      immunogenic proteins in a high-throughput manner using proteomics-microarray
      techniques. In the present study, an integrated immunoproteomics and
      bioinformatics approach was used to profile the tegument of the human blood fluke
      Schistosoma japonicum. Results showed that the full-length tegument proteins were
      high-throughput cloned and expressed and screened with sera from S. japonicum
      infected patients and normal subjects using protein arrays. Here, thirty highly
      immunoreactive tegument proteins and 10 antigens with an AUC value greater than
      0.90 were identified at first time. In particularly, STIP1, the highest
      immunoreactive tegument protein has been shown good antigenicity and
      immunogenicity, and thus makes it to be a potential target for designing anti
      parasite drug or vaccine. BIOLOGICAL SIGNIFICANCE: The schistosome tegument plays
      a crucial role in host-parasite interactions and there are several tegument
      proteins that proved to be potential vaccine candidates. However, vaccines are
      not yet available, thus it is important to identify new target antigens from
      schistosome tegument proteome. Herein, we demonstrate that the S. japonicum
      tegument proteins were analyzed by an integrated immunoproteomics and
      bioinformatics approach. We found that thirty highly immunoreactive tegument
      proteins and 10 antigens with an AUC value greater than 0.90 were identified for
      the first time. In particularly, we found 17 of tegument immunoproteomes having
      putative interaction networks with other proteins of S. japonicum. The results
      will provide clues of potential target molecules for vaccine development and
      biomarkers for diagnostics of schistosomiasis.

PMID- 24448402
TI  - Small bowel intussusception in a pregnant woman with Peutz-Jeghers Syndrome.
AB  - Intussusception is the most frequent complication of Peutz-Jeghers Syndrome
      (PJS), but usually seen in child age. It is a predictable, but infrequent
      complication in adults with PJS. However, there is no report about
      intussusception in pregnancy period secondary to Peutz-Jeghers (PJ) polyps in the
      literature. In this paper, we present a rare intussusception case in a pregnant
      woman with PJS, which was diagnosed with magnetic resonance imaging, and discuss
      this condition with a brief literature review. 

PMID- 24448401
TI  - Novel pathophysiological markers are revealed by iTRAQ-based quantitative
      clinical proteomics approach in vascular dementia.
AB  - Vascular dementia (VaD) is a leading cause of dementia in the elderly together
      with Alzheimer's disease with limited treatment options. Poor understanding of
      the pathophysiology underlying VaD is hindering the development of new therapies.
      Hence, to unravel its underlying molecular pathology, an iTRAQ-2D-LC-MS/MS
      strategy was used for quantitative analysis of pooled lysates from Brodmann area
      21 of pathologically confirmed cases of VaD and matched non-neurological
      controls. A total of 144 differentially expressed proteins out of 2281
      confidently identified proteins (false discovery rate=0.3%) were shortlisted for
      bioinformatics analysis. Western blot analysis of selected proteins using samples
      from individual patients (n=10 per group) showed statistically significant
      increases in the abundance of SOD1 and NCAM and reduced ATP5A in VaD. This
      suggested a state of hypometabolism and vascular insufficiency along with an
      inflammatory condition during VaD. Elevation of SOD1 and increasing trend for
      iron-storage proteins (FTL, FTH1) may be indicative of an oxidative imbalance
      that is accompanied by an aberrant iron metabolism. The synaptic proteins did not
      exhibit a generalized decrease in abundance (e.g. syntaxin) in the VaD subjects.
      This reported proteome offers a reference data set for future basic or
      translational studies on VaD. BIOLOGICAL SIGNIFICANCE: Our study is the first
      quantitative clinical proteomic study where iTRAQ-2D-LC-MS/MS strategy has been
      used to identify the differential proteome in the VaD cortex by comparing VaD and
      matched control subjects. We generate testable hypothesis about the involvement
      of various proteins in the vascular and parenchymal events during the evolution
      of VaD that finally leads to malfunction and demise of brain cells. This study
      also establishes quantitative proteomics as a complementary approach and viable
      alternative to existing neurochemical, electron microscopic and neuroimaging
      techniques that are traditionally being used to understand the molecular
      pathology of VaD. Our study could inspire fellow researchers to initiate similar
      retrospective studies targeting various ethnicities, age-groups or sub-types of
      VaD using brain samples available from brain banks across the world. Meta
      analysis of these studies in the future may be able to shortlist candidate
      proteins or pathways for rationale exploration of therapeutic targets or
      biomarkers for VaD.

PMID- 24448403
TI  - Exploring the impact of a community hospital closure on older adults: a focus
      group study.
AB  - The closing of hospitals has exacerbated challenges for older adults in accessing
      healthcare, especially those living in economically underserved settings. Through
      focus groups and a community-engaged approach, our study examined and documented
      the emergent health needs of older adults following the closing of a local
      hospital in an economically disadvantaged community. Focus groups were reconvened
      to assess progress and health needs over time. Analyses of the focus groups
      (n=37, mean age 77, 84% female) illustrated the impact of the closure and the
      emergence of the following dominant themes: perceptions of the hospital system,
      including feelings of abandonment and social isolation; transportation challenges
      in accessing health care resources; and lack of knowledge and literacy regarding
      available health care and obtaining health services. Discussion sessions with
      hospital administrators and participants afforded an opportunity for sharing data
      and additional assessment. The data and relationships developed with community
      participants and health system representatives resulted in the production of an
      information resource about access to health services, tailored for older adults. 

PMID- 24448404
TI  - The relationship between physical activity and the living environment: a multi
      level analyses focusing on changes over time in environmental factors.
AB  - There is limited evidence on the causality of previously observed associations
      between neighborhood characteristics and physical activity (PA). We aimed to
      assess whether individual-level PA was associated with changes in fear of crime,
      social cohesion, green spaces, parking facilities, social disorder, and physical
      disorder that occurred over the past 3 years. In general, in neighborhoods where
      residents had more favorable perceptions of the environment in 2006, residents
      were more likely to be physically active in 2009. In addition, improvements
      between 2006 and 2009 with respect to perceived social cohesion, green spaces,
      social disorder, and physical disorder were associated with increased odds of
      being active in 2009. For both the levels in 2006 and trends in the period 2006
      2009, the associations were somewhat stronger among women than among men, but
      associations did not vary by age or length of residence. For several
      environmental factors, we observed that not only the levels at a certain point in
      time, but also recent improvements over time were related to PA. These results
      provide new support for a causal relationship between these environmental factors
      and PA. 

PMID- 24448405
TI  - Extinction risk and conservation of the world's sharks and rays.
AB  - The rapid expansion of human activities threatens ocean-wide biodiversity.
      Numerous marine animal populations have declined, yet it remains unclear whether
      these trends are symptomatic of a chronic accumulation of global marine
      extinction risk. We present the first systematic analysis of threat for a
      globally distributed lineage of 1,041 chondrichthyan fishes-sharks, rays, and
      chimaeras. We estimate that one-quarter are threatened according to IUCN Red List
      criteria due to overfishing (targeted and incidental). Large-bodied, shallow
      water species are at greatest risk and five out of the seven most threatened
      families are rays. Overall chondrichthyan extinction risk is substantially higher
      than for most other vertebrates, and only one-third of species are considered
      safe. Population depletion has occurred throughout the world's ice-free waters,
      but is particularly prevalent in the Indo-Pacific Biodiversity Triangle and
      Mediterranean Sea. Improved management of fisheries and trade is urgently needed
      to avoid extinctions and promote population recovery. DOI:
      http://dx.doi.org/10.7554/eLife.00590.001. 

PMID- 24448406
TI  - The splicing regulator PTBP2 controls a program of embryonic splicing required
      for neuronal maturation.
AB  - We show that the splicing regulator PTBP2 controls a genetic program essential
      for neuronal maturation. Depletion of PTBP2 in developing mouse cortex leads to
      degeneration of these tissues over the first three postnatal weeks, a time when
      the normal cortex expands and develops mature circuits. Cultured Ptbp2(-/-)
      neurons exhibit the same initial viability as wild type, with proper neurite
      outgrowth and marker expression. However, these mutant cells subsequently fail to
      mature and die after a week in culture. Transcriptome-wide analyses identify many
      exons that share a pattern of mis-regulation in the mutant brains, where isoforms
      normally found in adults are precociously expressed in the developing embryo.
      These transcripts encode proteins affecting neurite growth, pre- and post
      synaptic assembly, and synaptic transmission. Our results define a new genetic
      regulatory program, where PTBP2 acts to temporarily repress expression of adult
      protein isoforms until the final maturation of the neuron. DOI:
      http://dx.doi.org/10.7554/eLife.01201.001. 

PMID- 24448407
TI  - A diversity of localized timescales in network activity.
AB  - Neurons show diverse timescales, so that different parts of a network respond
      with disparate temporal dynamics. Such diversity is observed both when comparing
      timescales across brain areas and among cells within local populations; the
      underlying circuit mechanism remains unknown. We examine conditions under which
      spatially local connectivity can produce such diverse temporal behavior. In a
      linear network, timescales are segregated if the eigenvectors of the connectivity
      matrix are localized to different parts of the network. We develop a framework to
      predict the shapes of localized eigenvectors. Notably, local connectivity alone
      is insufficient for separate timescales. However, localization of timescales can
      be realized by heterogeneity in the connectivity profile, and we demonstrate two
      classes of network architecture that allow such localization. Our results suggest
      a framework to relate structural heterogeneity to functional diversity and,
      beyond neural dynamics, are generally applicable to the relationship between
      structure and dynamics in biological networks. DOI:
      http://dx.doi.org/10.7554/eLife.01239.001. 

PMID- 24448408
TI  - Modes of flagellar assembly in Chlamydomonas reinhardtii and Trypanosoma brucei.
AB  - Defects in flagella growth are related to a number of human diseases. Central to
      flagellar growth is the organization of microtubules that polymerize from basal
      bodies to form the axoneme, which consists of hundreds of proteins. Flagella
      exist in all eukaryotic phyla, but neither the mechanism by which flagella grow
      nor the conservation of this process in evolution are known. Here, we study how
      protein complexes assemble onto the growing axoneme tip using (cryo) electron
      tomography. In Chlamydomonas reinhardtii microtubules and associated proteins are
      added simultaneously. However, in Trypanosoma brucei, disorganized arrays of
      microtubules are arranged into the axoneme structure by the later addition of
      preformed protein complexes. Post assembly, the T. brucei transition zone alters
      structure and its association with the central pair loosens. We conclude that
      there are multiple ways to form a flagellum and that species-specific structural
      knowledge is critical before evaluating flagellar defects. DOI:
      http://dx.doi.org/10.7554/eLife.01479.001. 

PMID- 24448409
TI  - Computation identifies structural features that govern neuronal firing properties
      in slowly adapting touch receptors.
AB  - Touch is encoded by cutaneous sensory neurons with diverse morphologies and
      physiological outputs. How neuronal architecture influences response properties
      is unknown. To elucidate the origin of firing patterns in branched
      mechanoreceptors, we combined neuroanatomy, electrophysiology and computation to
      analyze mouse slowly adapting type I (SAI) afferents. These vertebrate touch
      receptors, which innervate Merkel cells, encode shape and texture. SAI afferents
      displayed a high degree of variability in touch-evoked firing and peripheral
      anatomy. The functional consequence of differences in anatomical architecture was
      tested by constructing network models representing sequential steps of
      mechanosensory encoding: skin displacement at touch receptors,
      mechanotransduction and action-potential initiation. A systematic survey of arbor
      configurations predicted that the arrangement of mechanotransduction sites at
      heminodes is a key structural feature that accounts in part for an afferent's
      firing properties. These findings identify an anatomical correlate and plausible
      mechanism to explain the driver effect first described by Adrian and Zotterman.
      DOI: http://dx.doi.org/10.7554/eLife.01488.001. 

PMID- 24448410
TI  - p97-dependent retrotranslocation and proteolytic processing govern formation of
      active Nrf1 upon proteasome inhibition.
AB  - Proteasome inhibition elicits an evolutionarily conserved response wherein
      proteasome subunit mRNAs are upregulated, resulting in recovery (i.e., 'bounce
      back') of proteasome activity. We previously demonstrated that the transcription
      factor Nrf1/NFE2L1 mediates this homeostatic response in mammalian cells. We show
      here that Nrf1 is initially translocated into the lumen of the ER, but is rapidly
      and efficiently retrotranslocated to the cytosolic side of the membrane in a
      manner that depends on p97/VCP. Normally, retrotranslocated Nrf1 is degraded
      promptly by the proteasome and active species do not accumulate. However, in
      cells with compromised proteasomes, retrotranslocated Nrf1 escapes degradation
      and is cleaved N-terminal to Leu-104 to yield a fragment that is no longer
      tethered to the ER membrane. Importantly, this cleavage event is essential for
      Nrf1-dependent activation of proteasome gene expression upon proteasome
      inhibition. Our data uncover an unexpected role for p97 in activation of a
      transcription factor by relocalizing it from the ER lumen to the cytosol. DOI:
      http://dx.doi.org/10.7554/eLife.01856.001. 

PMID- 24448411
TI  - Nrf1 to the rescue.
AB  - When the level of proteasomal activity in a cell drops off, a transcription
      factor called Nrf1 travels to the nucleus to activate the genes that code for
      proteasomes. 

PMID- 24448412
TI  - One size does not fit all.
AB  - Comparing the anatomies of more than 100 different species of ants reveals that
      worker ants have enlarged necks, not seen in queens, that allow them to lift and
      carry objects many times heavier than themselves. 

PMID- 24448413
TI  - Correction: Evolution of thorax architecture in ant castes highlights trade-off
      between flight and ground behaviors.

PMID- 24448414
TI  - Enhanced thermal transport at covalently functionalized carbon nanotube array
      interfaces.
AB  - It has been more than a decade since the experimental demonstration that the
      thermal conductivity of carbon nanotubes can exceed that of diamond, which has
      the highest thermal conductivity among naturally occurring materials. In spite of
      tremendous promise as a thermal material, results have been disappointing for
      practical thermal systems and applications based on nanotubes. The main culprit
      for the dramatic shortfall in the performance of nanotubes in practical systems
      is high thermal interface resistance between them and other components because of
      weak adhesion at the interface. Here we report a sixfold reduction in the thermal
      interface resistance between metal surfaces and vertically aligned multiwall
      carbon nanotube arrays by bridging the interface with short, covalently bonded
      organic molecules. These results are also significant for single and multilayer
      graphene applications, since graphene faces similar limitations in practical
      systems. 

PMID- 24448415
TI  - A fast and reproducible method to quantify magnetic nanoparticle biodistribution.
AB  - The quantification of nanoparticles, particularly superparamagnetic iron oxide
      nanoparticles (SPIONs), both in vitro and in vivo has become highly important in
      recent years. Some methods, such as induced coupled plasma (ICP) spectroscopy and
      UV-visible chemical titration using Prussian Blue (PB), already exist however
      they consist of the titration of the whole iron content. These standard methods
      need sample preparations leading to their destruction and long measurement time.
      In this study, we used magnetic susceptibility measurements (MSM) to titrate the
      concentration and biodistribution of magnetic particles in the organs of rats.
      The advantages of the MSM SPION quantification technique are presented and
      compared to widely used methods of iron oxide titration such as ICP and PB UV
      visible titration. We have demonstrated that MSM is a simpler, faster (1 second
      per measurement), more reproducible and highly sensitive technique for SPION
      detection with minimal detection around 2 MUgFe mL(-1) without being influenced
      by neither the SPION coating nor their surrounding environment. Moreover, MSM is
      a more robust method as it is not affected by endogenous iron facilitating the
      distinction of SPIONs (iron present as nanoparticles) from background iron in
      tissues. This advantage allows the decrease of control samples needed in
      biological studies. In conclusion, we have demonstrated that MSM is a standard
      method that can be easily setup to determine the biodistribution of SPIONs
      regardless of their environment. 

PMID- 24448416
TI  - SiO2 nanoparticles change colour preference and cause Parkinson's-like behaviour
      in zebrafish.
AB  - With advances in the development of various disciplines, there is a need to
      decipher bio-behavioural mechanisms via interdisciplinary means. Here, we present
      an interdisciplinary study of the role of silica nanoparticles (SiO2-NPs) in
      disturbing the neural behaviours of zebrafish and a possible physiological
      mechanism for this phenomenon. We used adult zebrafish as an animal model to
      evaluate the roles of size (15-nm and 50-nm) and concentration (300 MUg/mL and
      1000 MUg/mL) in SiO2-NP neurotoxicity via behavioural and physiological analyses.
      With the aid of video tracking and data mining, we detected changes in
      behavioural phenotypes. We found that compared with 50-nm nanosilica, 15-nm SiO2
      NPs produced greater significant changes in advanced cognitive neurobehavioural
      patterns (colour preference) and caused potentially Parkinson's disease-like
      behaviour. Analyses at the tissue, cell and molecular levels corroborated the
      behavioural results, demonstrating that nanosilica acted on the retina and
      dopaminergic (DA) neurons to change colour preference and to cause potentially
      Parkinson's disease-like behaviour.

PMID- 24448418
TI  - Exempting patients from a smoke-free hospital policy on compassionate grounds.

PMID- 24448417
TI  - Antiproliferative efficacies but minor drug transporter inducing effects of
      paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and
      neck squamous cell carcinoma.
AB  - Drug-induced multidrug resistance (MDR) has been linked to overexpression of drug
      transporting proteins in head and neck squamous cell carcinoma (HNSCC) in vitro.
      The aim of this work was to reassess these findings in a murine xenograft model.
      NOD-SCID mice xenotransplanted with 10 (6) HNO97 cells were treated for four
      consecutive weeks with weekly paclitaxel, biweekly cisplatin (both
      intraperitoneal), or 5-fluorouracil (5-FU, administered by osmotic pump). Tumor
      volume and body weight were weekly documented. Expression of drug transporters
      and Ki-67 marker were examined using quantitative real-time polymerase chain
      reaction and/or immunohistochemistry. Both paclitaxel and cisplatin significantly
      reduced tumor volumes after 2-3 weeks. 5-FU-treated animals had significantly
      lower body weights after 2 or 4 weeks of chemotherapy. None of the drugs affected
      expression of drug transporters at the mRNA level. However, P-glycoprotein (Pgp)
      protein expression was increased by paclitaxel (P<0.01). Ki-67 expression did not
      change during treatment irrespective of the drug applied. Paclitaxel and
      cisplatin are effectively tumor volume reducing drugs in a murine xenograft model
      of HNSCC. Paclitaxel enhanced Pgp expression at the protein level, but not at the
      mRNA level suggesting transcriptional induction to be of minor relevance. In
      contrast, posttranscriptional mechanisms or Darwinian selection of intrinsically
      drug transporter overexpressing MDR cells might lead to iatrogenic chemotherapy
      resistance in HNSCC.

PMID- 24448419
TI  - Biological evaluation of diazene derivatives as anti-tubercular compounds.
AB  - Despite efforts made in chemotherapeutic research in the past and present,
      Mycobacterium tuberculosis (M.tb), the etiological agent of tuberculosis, still
      causes more than a million deadly casualties each year, second only to HIV. The
      rapid generation and spread of drug resistant strains, a problem exacerbated by
      co-infection with HIV demands further efforts in the investigation of novel
      classes of anti-tubercular compounds. A library of eight substituted
      diazenecarboxamides, three carbamoyldiazenecarboxylates and four diazene-1,2
      dicarboxamides was synthesized in a straightforward manner followed by a
      biological evaluation of the compounds. We observed minimal inhibitory
      concentrations below 10 MUg/mL against the H37Rv lab strain of M.tb. Three
      compounds that showed a potency of 90% growth inhibition of M.tb at a
      concentration lower than 10 MUg/mL were further evaluated and showed potency
      against other clinically relevant mycobacterial species such as Mycobacterium
      bovis, Mycobacterium avium and Mycobacterium ulcerans. The selected compounds
      were examined for acute cell toxicity on a murine macrophage like monocyte cell
      line J774 A.1 in which the cell viability was reduced by 50% at concentrations
      ranging from 7.4 MUg/mL to 20.7 MUg/mL. Neither of the three compounds showed
      signs of genotoxicity by VITOTOX or by Comet assay. The study was complemented by
      demonstration of the inhibition of intracellular replication of M.tb H37Rv inside
      J774 A.1 cells at 2 MUg/mL concentration and the susceptibility of a MDR LAM-1
      strain at concentrations between 5 and 1 MUg/mL of the most active compound.

PMID- 24448420
TI  - Recent advances in small organic molecules as DNA intercalating agents:
      synthesis, activity, and modeling.
AB  - The interaction of small molecules with DNA plays an essential role in many
      biological processes. As DNA is often the target for majority of anticancer and
      antibiotic drugs, study about the interaction of drug and DNA has a key role in
      pharmacology. Moreover, understanding the interactions of small molecules with
      DNA is of prime significance in the rational design of more powerful and
      selective anticancer agents. Two of the most important and promising targets in
      cancer chemotherapy include DNA alkylating agents and DNA intercalators. For
      these last the DNA recognition is a critical step in their anti-tumor action and
      the intercalation is not only one kind of the interactions in DNA recognition but
      also a pivotal step of several clinically used anti-tumor drugs such as
      anthracyclines, acridines and anthraquinones. To push clinical cancer therapy,
      the discovery of new DNA intercalators has been considered a practical approach
      and a number of intercalators have been recently reported. The intercalative
      binding properties of such molecules can also be harnessed as diagnostic probes
      for DNA structure in addition to DNA-directed therapeutics. Moreover, the problem
      of intercalation site formation in the undistorted B-DNA of different length and
      sequence is matter of tremendous importance in molecular modeling studies and,
      nowadays, three models of DNA intercalation targets have been proposed that
      account for the binding features of intercalators. Finally, despite DNA being an
      important target for several drugs, most of the docking programs are validated
      only for proteins and their ligands. Therefore, a default protocol to identify
      DNA binding modes which uses a modified canonical DNA as receptor is needed. 

PMID- 24448421
TI  - Novel hybrid selenosulfonamides as potent antileishmanial agents.
AB  - Diselenide and sulfonamide derivatives have recently attracted considerable
      interest as leishmanicidal agents in drug discovery. In this study, a novel
      series of sixteen hybrid selenosulfonamides has been synthesized and screened for
      their in vitro activity against Leishmania infantum intracellular amastigotes and
      THP-1 cells. These assays revealed that most of the compounds exhibited
      antileishmanial activity in the low micromolar range and led us to identify three
      lead compounds (derivatives 2, 7 and 14) with IC50 values ranging from 0.83 to
      1.47 MUM and selectivity indexes (SI) over 17, much higher than those observed
      for the reference drugs miltefosine and edelfosine. When evaluated against
      intracellular amastigotes, hybrid compound 7 emerged as the most active compound
      (IC50 = 2.8 MUM), showing higher activity and much less toxicity against THP-1
      cells than edelfosine. These compounds could potentially serve as templates for
      future drug-optimization and drug-development efforts for their use as
      therapeutic agents in developing countries.

PMID- 24448422
TI  - New perspectives on the synthesis and antichagasic activity of 3-alkoxy-1-alkyl-5
      nitroindazoles.
AB  - The synthesis and antiprotozoal activity of some 3-alkoxy-1-alkyl- (1, 4) and 3
      alkoxy-1-(omega-aminoalkyl)-5-nitroindazoles (2, 3, 5-8) against different
      morphological forms of Trypanosoma cruzi are reported. These compounds were
      prepared using simple alkylation reactions and, usually, taking advantage of the
      reactivity of some indazole-derived betaines previously studied by us. Most
      indazole derivatives showed in vitro activities similar or higher than those of
      the reference drug benznidazole; this fact, along with low unspecific
      cytotoxicities against Vero cells shown by some of them, led to very good
      selectivity indexes (SI). The high efficiency of 5-nitroindazoles 1 and 2 against
      T. cruzi was confirmed by further in vitro studies on infection rates and by an
      additional in vivo study in a murine model of acute and chronic Chagas disease.
      Complementary analyses of the changes in the metabolites excreted by the parasite
      and on the ultrastructural alterations induced after treatment with indazole
      derivatives 1 and 2 were also conducted.

PMID- 24448423
TI  - Poly (ADP-ribose) polymerase 1 transcriptional regulation: a novel crosstalk
      between histone modification H3K9ac and ETS1 motif hypomethylation in BRCA1
      mutated ovarian cancer.
AB  - Poly (ADP-ribose) polymerase 1 (PARP1) plays a critical role in ovarian cancer
      progression. However, the epigenetic mechanism regulating PARP1 transcription
      remains largely unknown. Here, we show that the hypomethylated ETS1 motif is a
      key regulatory element for the PARP1 gene in BRCA1-mutated ovarian cancer.
      Mechanistically, the ETS1 motif hypomethylation-mediated increase of active
      histone marker H3K9ac and transcription factor ETS1 enrichment synergistically
      activates PARP1 transcription. Clinicopathological data indicate that a
      hypomethylated ETS1 motif was associated with high-grade tumors (P = 0.026) and
      pN1 (P = 0.002). Univariate survival analysis demonstrated an association between
      the hypomethylated ETS1 motif and an increased risk of death in BRCA1-mutated
      ovarian cancer patients. Our findings imply that the genetic (such as BRCA1
      mutation) and epigenetic mechanisms (such as hypomethylated ETS1 motif, and
      histone modification H3K9ac and transcription factor ETS1 binding) are jointly
      involved in the malignant progression of PARP1-related ovarian cancer. 

PMID- 24448424
TI  - An efficient strategy for the synthesis of polysubstituted chromeno[4,3
      b]pyrrolidine derivatives.
AB  - A powerful cascade reaction was developed for the synthesis of chromeno[4,3
      b]pyrrolidines with high yields and excellent stereoselectivities. This efficient
      cascade reaction expeditiously established two fused rings which bear three
      contiguous stereogenic centers including one quaternary stereocenter in a single
      operation with low catalyst loading under mild conditions. 

PMID- 24448425
TI  - Rotational spectroscopy with an optical centrifuge.
AB  - We demonstrate a new spectroscopic method for studying electronic transitions in
      molecules with extremely broad range of angular momentum. We employ an optical
      centrifuge to create narrow rotational wave packets in the ground electronic
      state of (16)O2. Using the technique of resonance-enhanced multi-photon
      ionization, we record the spectrum of multiple ro-vibrational transitions between
      X(3)Sigmag(-) and C(3)Pig electronic manifolds of oxygen. Direct control of
      rotational excitation, extending to rotational quantum numbers as high as N ?
      120, enables us to interpret the complex structure of rotational spectra of
      C(3)Pig beyond thermally accessible levels. 

PMID- 24448426
TI  - Evaluation of competencies in the field of vocational rehabilitation and the
      employment of persons with disabilities.
AB  - For decades, employment of a person with disabilities has been considered a key
      indicator of the success of vocational rehabilitation. There is a link between
      the quality of vocational rehabilitation and a better quality of life for service
      users; these services have a significant impact on efficiency in the field of
      work. Very few authors have researched the qualification and skills of
      rehabilitation experts essential for successfully carrying out their professional
      activities. The objective of the present study was to investigate the perceived
      importance attached to the competencies of vocational rehabilitation
      professionals and the frequency of their application at work in three different
      countries, which was conducted using a questionnaire that was prepared on the
      basis of a questionnaire designed by Australian researchers. Basic competencies
      comprise four sets: vocational counselling, professional practice, personal
      counselling and rehabilitation case management. Special competencies are composed
      of two sets: workplace disability case management and workplace intervention and
      programme management. The questionnaire was completed by 131 respondents, of whom
      61 were from Slovenia, 34 were from Austria and 36 were from the UK. t-Tests for
      two independent samples (sex), analysis of variance (type of education, country)
      and Pearson's correlation coefficient were used to compare the perception of
      basic and special competencies. The respondents perceived personal counselling,
      vocational counselling and management of rehabilitation cases as being the most
      important, whereas the least importance was assigned to interventions. In
      practice, the respondents used personal counselling most frequently and very few
      interventions. 

PMID- 24448427
TI  - Bidirectional non-innocence of the beta-diketonato ligand 9-oxidophenalenone (L-)
      in [Ru([9]aneS3)(L)(dmso)]n, [9]aneS3 = 1,4,7-trithiacyclononane.
AB  - The new compound [Ru(II)([9]aneS3)(L)(dmso)]ClO4 ([]ClO4) ([9]aneS3 = 1,4,7
      trithiacyclononane, HL = 9-hydroxyphenalenone, dmso = dimethylsulfoxide) has been
      structurally characterised to reveal almost equal C-O bond distances of
      coordinated L(-), suggesting a delocalised bonding situation of the beta
      diketonato ligand. The dmso ligand is coordinated via the sulfur atom in the
      native (1+) and reduced states (1 and 1-) as has been revealed by X-ray
      crystallography and by DFT calculations. Cyclic voltammetry of 1+ exhibits two
      close-lying one-electron oxidation waves at 0.77 V and 0.94 V, and two similarly
      close one-electron reduction processes at -1.43 V and -1.56 V versus SCE in
      CH2Cl2. The electronic structures of 1n in the accessible redox states have been
      analysed via experiments (EPR and UV-vis-NIR spectroelectrochemistry) and by
      DFT/TD-DFT calculations, revealing the potential for bidirectional non-innocent
      behaviour of coordinated L(/-/2-). Specifically, the studies establish
      significant involvement of L based frontier orbitals in both the oxidation and
      reduction processes: [([9]aneS3)(dmso)Ru(III)-L](3+) (1(3+)) ?
      [([9]aneS3)(dmso)Ru(III)-L(-)](2+)/[([9]aneS3)(dmso)Ru(II)-L](2+) (1(2+)) ?
      [([9]aneS3)(dmso)Ru(II)-L(-)](+) (1(+)) ? [([9]aneS3)(dmso)Ru(II)-L(2-)] (1) ?
      [([9]aneS3)(dmso)Ru(II)-L(3-)](-)/[([9]aneS3)(dmso)Ru(I)-L(2-)](-) (1-).

PMID- 24448428
TI  - Copper-catalyzed direct C-H arylation of pyridine N-oxides with arylboronic
      esters: one-pot synthesis of 2-arylpyridines.
AB  - The first example of the copper-catalyzed direct C-H arylation of pyridine N
      oxides with arylboronic esters has been developed, leading to a wide range of 2
      arylpyridines in a one-pot synthesis with moderate to good yields without an
      additional reductant. This transformation allows for rapid access to a variety of
      2-arylpyridines using an inexpensive catalytic system that would be more
      difficult to access with traditional methods. Thus, this method represents a
      simple and practical procedure to access 2-arylpyridines. 

PMID- 24448430
TI  - Single-shot tomographic movies of evolving light-velocity objects.
AB  - Tomography--cross-sectional imaging based on measuring radiation transmitted
      through an object along different directions--enables non-invasive imaging of
      hidden stationary objects, such as internal bodily organs, from their
      sequentially measured projections. Here we adapt tomographic methods to visualize
      -in one laser shot--the instantaneous structure and evolution of a laser-induced
      object propagating through a transparent Kerr medium. We reconstruct 'movies' of
      a laser pulse's diffraction, self-focusing and filamentation from phase 'streaks'
      imprinted onto probe pulses that cross the main pulse's path simultaneously at
      different angles. Multiple probes are generated and detected compactly and
      simply, making the system robust, easy to align and adaptable to many problems.
      Our technique could potentially visualize, for example, plasma wakefield
      accelerators, optical rogue waves or fast ignitor pulses, light-velocity objects,
      whose detailed space-time dynamics are known only through intensive computer
      simulations.

PMID- 24448429
TI  - Pain location and functioning in persons with spinal cord injury.
AB  - BACKGROUND: The influence of pain location and extent on functioning in persons
      with spinal cord injury (SCI) and chronic pain is not well understood. OBJECTIVE:
      To investigate the correlations between pain location and extent to determine
      which pain domains may be important to assess and potentially target in treating
      chronic pain in SCI populations. DESIGN: Prospective, observational study.
      SETTING: University medical center. PARTICIPANTS: A total of 259 persons with an
      SCI and chronic pain. METHODS: Postal mail survey questionnaire. MAIN OUTCOME
      MEASUREMENTS: Pain sites, pain extent (number of sites), pain intensity in
      specific body locations, pain interference, and physical and psychological
      functioning. RESULTS: A positive association between pain extent and intensity
      with pain interference (r = 0.33, P < .01) and a negative association with
      psychological functioning were noted in the study sample (r = -0.21, P < .01).
      Pain intensity in the lower back and legs (r = 0.55, P < .01) and a number of
      other sites showed strong associations with patient functioning. Correlation with
      psychological functioning was significant but weaker (r = -0.22, P < .01 for the
      lower back and legs). Ambulatory status had only a small moderating effect on the
      associations between pain intensity in specific sites and pain interference and
      no effect on psychological functioning. CONCLUSIONS: The findings support the
      importance of assessing pain intensity at specific locations as a part of a
      thorough evaluation of chronic pain, as well as the importance of addressing pain
      at multiple sites, when managing pain in persons with an SCI.

PMID- 24448431
TI  - Frequency-encoded laser-induced fluorescence for multiplexed detection in
      infrared-mediated quantitative PCR.
AB  - A frequency-modulated fluorescence encoding method was used as a means to
      increase the number of fluorophores monitored during infrared-mediated polymerase
      chain reaction. Laser lines at 488 nm and 561 nm were modulated at 73 and 137 Hz,
      respectively, exciting fluorescence from the dsDNA intercalating dye, EvaGreen,
      and the temperature insensitive dye, ROX. Emission was collected in a color-blind
      manner using a single photomultiplier tube for detection and demodulated by
      frequency analysis. The resulting frequency domain signal resolved the
      contribution from the two fluorophores as well as the background from the IR
      lamp. The detection method was successfully used to measure amplification of DNA
      samples containing 10(4)-10(7) starting copies of template producing an
      amplification efficiency of 96%. The utility of this methodology was further
      demonstrated by simultaneous amplification of two genes from human genomic DNA
      using different color TaqMan probes. This method of multiplexing fluorescence
      detection with IR-qPCR is ideally suited as it allows isolation of the signals of
      interest from the background in the frequency domain and is expected to further
      reduce the complexity of multiplexed microfluidic IR-qPCR instrumentation. 

PMID- 24448432
TI  - Acute inferior myocardial infarction in a young male patient associated with
      Behcet's disease and sildenafil.
AB  - Behcet's disease (BD) is a multisystemic inflammatory disorder of unknown origin,
      presenting with mucocutaneous, ocular, articular, vascular, gastrointestinal and
      central nervous system manifestations. Coronary involvement is very rare in
      patients with BD. Sildenafil, an oral drug used to treat erectile dysfunction,
      was shown to cause significant cardiovascular problems including acute myocardial
      infarction (MI) and sudden cardiac death. Acute MI associated with BD and
      sildenafil has not been reported previously. We present a case of a 23-year-old
      male patient with an acute inferior MI associated with BD diagnosed after
      admission of sildenafil, who was successfully treated with thrombus aspiration
      and tirofiban administration. 

PMID- 24448434
TI  - Metastatic lung cancer, an interesting stroke mimic.
AB  - An elderly man presented to the emergency department with symptoms of a left
      sided weakness. A CT of the brain scan showed an abnormality, and he was
      diagnosed with a stroke and admitted to the stroke unit. The stroke consultant
      reviewed him the next morning; a detailed history was acquired and imaging
      reviewed. As a result of the history of neurological symptoms, a diagnosis of
      malignancy was suspected and an MRI of the brain was ordered. This did not show a
      stroke but suggested a mass lesion. A CT of the chest, abdomen and pelvis was
      ordered to rule out a primary cause. Unfortunately, this showed widespread
      metastatic carcinoma with a left upper lobe primary (T4 N3 M1b). This was
      confirmed on histology. The patient died soon after the diagnosis. 

PMID- 24448435
TI  - Dentigerous cyst: a common lesion in an uncommon site.

PMID- 24448436
TI  - Monsters do exist: an unusual case of chest pain.
AB  - A 19-year-old man presented to the emergency department with a 3-week history of
      chest pain. Despite normal examination, bloods and observations of his chest X
      ray revealed a large opacity in the middle and lower right zone. Further imaging
      revealed a multicystic mediastinal teratoma. He was admitted under the
      respiratory physicians who arranged further investigations and discussed his case
      with the lung and testicular multidisciplinary team. He was started on
      neoadjuvant chemotherapy with a plan for future definitive surgical resection.
      Four months later he suddenly deteriorated due to airway compression from the
      tumour. He underwent an emergency thoracotomy and tumour resection. He is
      currently doing well and is thought to have a good prognosis following complete
      resection of his tumour. This case report summarises this rare diagnosis and
      emphasises the need for careful evaluation of patients despite their initial well
      appearance, especially in patients who are reattending. 

PMID- 24448437
TI  - Isolated cilioretinal artery occlusion in a patient with hypertensive crisis.

PMID- 24448438
TI  - Mec1 and Tel1: an arresting dance of resection.

PMID- 24448440
TI  - Toward an improved understanding of the physiology of aqueous humor flow.

PMID- 24448439
TI  - Implications of COMT long-range interactions on the phenotypic variability of
      22q11.2 deletion syndrome.
AB  - 22q11.2 deletion syndrome (22q11DS) results from a hemizygous microdeletion on
      chromosome 22 and is characterized by extensive phenotypic variability.
      Penetrance of signs, including congenital heart, craniofacial, and
      neurobehavioral abnormalities, varies widely and is not well correlated with
      genotype. The three-dimensional structure of the genome may help explain some of
      this variability. The physical interaction profile of a given gene locus with
      other genetic elements, such as enhancers and co-regulated genes, contributes to
      its regulation. Thus, it is possible that regulatory interactions with elements
      outside the deletion region are disrupted in the disease state and modulate the
      resulting spectrum of symptoms. COMT, a gene within the commonly deleted ~3 Mb
      region has been implicated as a contributor to the neurological features
      frequently found in 22q11DS patients. We used this locus as bait in a 4C-seq
      experiment to investigate genome-wide interaction profiles in B lymphocyte and
      fibroblast cell lines derived from both 22q11DS and unaffected individuals. All
      normal B lymphocyte lines displayed local, conserved chromatin looping
      interactions with regions that are lost in atypical and distal deletions, which
      may mediate similarities between typical, atypical, and distal 22q11 deletion
      phenotypes. There are also distinct clusterings of cis interactions based on
      disease state. We identified regions of differential trans interactions present
      in normal, and lost in deletion-carrying, B lymphocyte cell lines. This data
      suggests that hemizygous chromosomal deletions such as 22q11DS can have
      widespread effects on chromatin organization, and may contribute to the inherent
      phenotypic variability. 

PMID- 24448441
TI  - Challenging accepted ethical beliefs.

PMID- 24448442
TI  - A Bayesian model for joint analysis of multivariate repeated measures and time to
      event data in crossover trials.
AB  - Joint modeling of longitudinal and survival data has become a popular technique
      in analyzing longitudinal clinical trials. In this discussion, the potentials of
      joint modeling are explored for analyzing time to event and multivariate repeated
      measures in crossover studies. The work is motivated by a real-life crossover
      study with three visual analog scale responses and a time to event response. To
      recover the information lost due to censoring of the time to event variable, we
      propose a Bayesian joint model to analyze the visual analog scale and time to
      event responses jointly, leveraging the moderate associations among the
      responses. The joint model links the time to event variable to the visual analog
      scale repeated measures via multi-layered subject-specific random effects. We
      show the Bayesian joint model produces more efficient inferences with
      satisfactory goodness of fit in general with comparison to modeling of the visual
      analog scale and time to event responses separately. A simulation study is
      performed to demonstrate the inferential advantages of Bayesian joint model over
      separate modeling and maximum likelihood approaches via non-linear mixed modeling
      in the crossover setting. This work also demonstrates the flexibility and
      usefulness of zero-one inflated beta regression in modeling non-Gaussian fixed
      boundaries-inflated outcomes in general.

PMID- 24448443
TI  - Confidence intervals for proportion difference from two independent partially
      validated series.
AB  - Partially validated series are common when a gold-standard test is too expensive
      to be applied to all subjects, and hence a fallible device is used accordingly to
      measure the presence of a characteristic of interest. In this article, confidence
      interval construction for proportion difference between two independent partially
      validated series is studied. Ten confidence intervals based on the method of
      variance estimates recovery (MOVER) are proposed, with each using the confidence
      limits for the two independent binomial proportions obtained by the asymptotic,
      Logit-transformation, Agresti-Coull and Bayesian methods. The performances of the
      proposed confidence intervals and three likelihood-based intervals available in
      the literature are compared with respect to the empirical coverage probability,
      confidence width and ratio of mesial non-coverage to non-coverage probability.
      Our empirical results show that (1) all confidence intervals exhibit good
      performance in large samples; (2) confidence intervals based on MOVER combining
      the confidence limits for binomial proportions based on Wilson, Agresti-Coull,
      Logit-transformation, Bayesian (with three priors) methods perform satisfactorily
      from small to large samples, and hence can be recommended for practical
      applications. Two real data sets are analysed to illustrate the proposed methods.

PMID- 24448444
TI  - Level of evidence for promising subgroup findings in an overall non-significant
      trial.
AB  - In drug development and drug licensing, it sometimes occurs that a new drug does
      not demonstrate effectiveness for the full study population, but there appears to
      be benefit in a relevant, pre-defined subgroup. This raises the question, how
      strong the evidence from such a subgroup is, and which confirmatory testing
      strategies are the most appropriate ones. Hence, we considered the type I error
      and the power of a subgroup result in a trial with non-significant overall
      results and of suitable replication strategies. In the case of a single trial,
      the inflation of the overall type I error is substantial and can be up to twice
      as large, especially in relatively small subgroups. This also increases to the
      risk of starting a replication trial that should not be done, if such a second
      trial is not already available. The overall type I error is almost controlled by
      using an appropriate replication strategy. This confirms the required cautious
      interpretation of promising subgroups, even in the case that overall trial
      results were perceived to be close to significance.

PMID- 24448445
TI  - Graphical model-based O/E control chart for monitoring multiple outcomes from a
      multi-stage healthcare procedure.
AB  - Most statistical process control programmes in healthcare focus on surveillance
      of outcomes at the final stage of a procedure, such as mortality or failure
      rates. Such an approach ignores the multi-stage nature of these procedures, in
      which a patient progresses through several stages prior to the final stage. In
      this paper, we introduce a novel approach to statistical process control
      programmes in healthcare. Our proposed approach is based on the regression
      adjustment and multi-stage control charts that have been in use in industrial
      applications for decades. Three advantages of the approach are: better
      understanding of how outcomes at different stages relate to each other, explicit
      monitoring of upstream stage outcomes may help curtail trends that lead to poorer
      end-stage outcomes and understanding the impact of each stage can help determine
      the most effective allocation of quality improvement resources. A test statistic
      for the control charts is proposed. Simulations are performed to test the control
      charts, and the results are summarised using an empirical probability of true
      detection. An illustrative example using data from a maternity unit is included.
      A main result from the simulation study is that taking a multi-stage approach
      makes it easer to explicitly identify shifts in upstream stage outcomes that
      might otherwise be signalled in final stage outcomes if dependence between stages
      is ignored.

PMID- 24448446
TI  - Fast-evolving microRNAs are highly expressed in the early embryo of Drosophila
      virilis.
AB  - MicroRNAs are short non-protein-coding RNAs that regulate gene expression at the
      post-transcriptional level and are essential for the embryonic development of
      multicellular animals. Comparative genome-scale analyses have revealed that
      metazoan evolution is accompanied by the continuous acquisition of novel microRNA
      genes. This suggests that novel microRNAs may promote innovation and diversity in
      development. We determined the evolutionary origins of extant Drosophila
      microRNAs and estimated the sequence divergence between the 130 orthologous
      microRNAs in Drosophila melanogaster and Drosophila virilis, separated by 63
      million years of evolution. We then generated small RNA sequencing data sets
      covering D. virilis development and explored the relationship between microRNA
      conservation and expression in a developmental context. We find that late
      embryonic, larval, and adult stages are dominated by conserved microRNAs. This
      pattern, however, does not hold for the early embryo, where rapidly evolving
      microRNAs are uniquely present at high levels in both species. The group of fast
      evolving microRNAs that are highly expressed in the early embryo belong to two
      Drosophilid lineage-specific clusters: mir-310 ~ 313 and mir-309 ~ 6. These
      clusters have particularly complex evolutionary histories of duplication, gain,
      and loss. Our analyses suggest that the early embryo is a more permissive
      environment for microRNA changes and innovations. Fast-evolving microRNAs,
      therefore, have the opportunity to become preferentially integrated in early
      developmental processes, and may impact the evolution of development. The
      relationship between microRNA conservation and expression throughout the
      development of Drosophila differs from that previously observed for protein
      coding genes.

PMID- 24448447
TI  - Mass spectrometry-based relative quantification of proteins in precatalytic and
      catalytically active spliceosomes by metabolic labeling (SILAC), chemical
      labeling (iTRAQ), and label-free spectral count.
AB  - The spliceosome undergoes major changes in protein and RNA composition during pre
      mRNA splicing. Knowing the proteins-and their respective quantities-at each
      spliceosomal assembly stage is critical for understanding the molecular
      mechanisms and regulation of splicing. Here, we applied three independent mass
      spectrometry (MS)-based approaches for quantification of these proteins: (1)
      metabolic labeling by SILAC, (2) chemical labeling by iTRAQ, and (3) label-free
      spectral count for quantification of the protein composition of the human
      spliceosomal precatalytic B and catalytic C complexes. In total we were able to
      quantify 157 proteins by at least two of the three approaches. Our quantification
      shows that only a very small subset of spliceosomal proteins (the U5 and U2 Sm
      proteins, a subset of U5 snRNP-specific proteins, and the U2 snRNP-specific
      proteins U2A' and U2B'') remains unaltered upon transition from the B to the C
      complex. The MS-based quantification approaches classify the majority of proteins
      as dynamically associated specifically with the B or the C complex. In terms of
      experimental procedure and the methodical aspect of this work, we show that
      metabolically labeled spliceosomes are functionally active in terms of their
      assembly and splicing kinetics and can be utilized for quantitative studies.
      Moreover, we obtain consistent quantification results from all three methods,
      including the relatively straightforward and inexpensive label-free spectral
      count technique. 

PMID- 24448448
TI  - Simple methods for the 3' biotinylation of RNA.
AB  - Biotinylation of RNA allows its tight coupling to streptavidin and is thus useful
      for many types of experiments, e.g., pull-downs. Here we describe three simple
      techniques for biotinylating the 3' ends of RNA molecules generated by chemical
      or enzymatic synthesis. First, extension with either the Schizosaccharomyces
      pombe noncanonical poly(A) polymerase Cid1 or Escherichia coli poly(A) polymerase
      and N6-biotin-ATP is simple, efficient, and generally applicable independently of
      the 3'-end sequences of the RNA molecule to be labeled. However, depending on the
      enzyme and the reaction conditions, several or many biotinylated nucleotides are
      incorporated. Second, conditions are reported under which splint-dependent
      ligation by T4 DNA ligase can be used to join biotinylated and, presumably, other
      chemically modified DNA oligonucleotides to RNA 3' ends even if these are
      heterogeneous as is typical for products of enzymatic synthesis. Third, we
      describe the use of 29 DNA polymerase for a template-directed fill-in reaction
      that uses biotin-dUTP and, thanks to the enzyme's proofreading activity, can cope
      with more extended 3' heterogeneities. 

PMID- 24448449
TI  - Improved design of hammerhead ribozyme for selective digestion of target RNA
      through recognition of site-specific adenosine-to-inosine RNA editing.
AB  - Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism
      involved in various biological processes. Site-specific, editing-state-dependent
      degradation of target RNA may be a powerful tool both for analyzing the mechanism
      of RNA editing and for regulating biological processes. Previously, we designed
      an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage
      dependent on the A-to-I RNA editing state. In the present work, we developed an
      improved strategy for constructing a trans-acting HHR that specifically cleaves
      target editing sites in the adenosine but not the inosine state. Specificity for
      unedited sites was achieved by utilizing a sequence encoding the intrinsic
      cleavage specificity of a natural HHR. We used in vitro selection methods in an
      HHR library to select for an extended HHR containing a tertiary stabilization
      motif that facilitates HHR folding into an active conformation. By using this
      method, we successfully constructed highly active HHRs with unedited-specific
      cleavage. Moreover, using HHR cleavage followed by direct sequencing, we
      demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA
      extracted from mouse brain, depending on the site-specific editing state. This
      unedited-specific cleavage also enabled us to analyze the effect of editing state
      at the E and C sites on editing at other sites by using direct sequencing for the
      simultaneous quantification of the editing ratio at multiple sites. Our approach
      has the potential to elucidate the mechanism underlying the interdependencies of
      different editing states in substrate RNA with multiple editing sites. 

PMID- 24448450
TI  - NMR structure of the 5' splice site in the group IIB intron Sc.ai5gamma-
      conformational requirements for exon-intron recognition.
AB  - A crucial step of the self-splicing reaction of group II intron ribozymes is the
      recognition of the 5' exon by the intron. This recognition is achieved by two
      regions in domain 1 of the intron, the exon-binding sites EBS1 and EBS2 forming
      base pairs with the intron-binding sites IBS1 and IBS2 located at the end of the
      5' exon. The complementarity of the EBS1*IBS1 contact is most important for
      ensuring site-specific cleavage of the phosphodiester bond between the 5' exon
      and the intron. Here, we present the NMR solution structures of the d3' hairpin
      including EBS1 free in solution and bound to the IBS1 7-mer. In the unbound
      state, EBS1 is part of a flexible 11-nucleotide (nt) loop. Binding of IBS1
      restructures and freezes the entire loop region. Mg(2+) ions are bound near the
      termini of the EBS1*IBS1 helix, stabilizing the interaction. Formation of the 7
      bp EBS1*IBS1 helix within a loop of only 11 nt forces the loop backbone to form a
      sharp turn opposite of the splice site, thereby presenting the scissile phosphate
      in a position that is structurally unique. 

PMID- 24448453
TI  - Managing the innovation supply chain to maximize personalized medicine.
AB  - Personalized medicine epitomizes an evolving model of care tailored to the
      individual patient. This emerging paradigm harnesses radical technological
      advances to define each patient's molecular characteristics and decipher his or
      her unique pathophysiological processes. Translated into individualized
      algorithms, personalized medicine aims to predict, prevent, and cure disease
      without producing therapeutic adverse events. Although the transformative power
      of personalized medicine is generally recognized by physicians, patients, and
      payers, the complexity of translating discoveries into new modalities that
      transform health care is less appreciated. We often consider the flow of
      innovation and technology along a continuum of discovery, development,
      regulation, and application bridging the bench with the bedside. However, this
      process also can be viewed through a complementary prism, as a necessary supply
      chain of services and providers, each making essential contributions to the
      development of the final product to maximize value to consumers. Considering
      personalized medicine in this context of supply chain management highlights
      essential points of vulnerability and/or scalability that can ultimately
      constrain translation of the biological revolution or potentiate it into
      individualized diagnostics and therapeutics for optimized value creation and
      delivery. 

PMID- 24448451
TI  - Bdellovibrio bacteriovorus inhibits Staphylococcus aureus biofilm formation and
      invasion into human epithelial cells.
AB  - Bdellovibrio bacteriovorus HD100 is a predatory bacterium that attacks many Gram
      negative human pathogens. A serious drawback of this strain, however, is its
      ineffectiveness against Gram-positive strains, such as the human pathogen
      Staphylococcus aureus. Here we demonstrate that the extracellular proteases
      produced by a host-independent B. bacteriovorus (HIB) effectively degrade/inhibit
      the formation of S. aureus biofilms and reduce its virulence. A 10% addition of
      HIB supernatant caused a 75% or greater reduction in S. aureus biofilm formation
      as well as 75% dispersal of pre-formed biofilms. LC-MS-MS analyses identified
      various B. bacteriovorus proteases within the supernatant, including the serine
      proteases Bd2269 and Bd2321. Tests with AEBSF confirmed that serine proteases
      were active in the supernatant and that they impacted S. aureus biofilm
      formation. The supernatant also possessed a slight DNAse activity. Furthermore,
      treatment of planktonic S. aureus with the supernatant diminished its ability to
      invade MCF-10a epithelial cells by 5-fold but did not affect the MCF-10a
      viability. In conclusion, this study illustrates the hitherto unknown ability of
      B. bacteriovorus to disperse Gram-positive pathogenic biofilms and mitigate their
      virulence. 

PMID- 24448456
TI  - The evolving role of biomarker patents in personalized medicine.
AB  - Patents are commonly granted for the use of biomarkers in making medical
      decisions. However, the US Supreme Court recently changed the landscape with a
      unanimous decision that patents cannot cover discoveries of basic correlations in
      nature, such as those relating biomarkers to particular clinical outcomes.
      Subsequent court decisions have overturned patents on genetic and other
      diagnostic methods involving purely mental processes, but processes integrating
      biomarkers in practical clinical steps can still earn intellectual property
      protections. 

PMID- 24448457
TI  - Personal DNA donation to energize genomic medicine.
AB  - Immense strides toward improved human genomic sequencing have been made over the
      past decade, but significant obstacles to clinical research and translation are
      now evident. Novel approaches able to traverse financial, regulatory, and ethical
      obstacles on behalf of patients and the public health are needed. We propose a
      novel approach to the collection and annotation of personal genomic data using an
      organized donation program analogous to the national organ-procurement system. 

PMID- 24448458
TI  - Integrated efficacy to effectiveness trials.
AB  - Experts in clinical research, therapeutic development, and comparative
      effectiveness are continually frustrated in their attempts to fit the square peg
      of therapeutic development into the round hole of clinical trials. Trials can be
      optimized to provide signals in highly controlled experiments or to estimate an
      intervention's effect in poorly controlled real-world settings, but not both
      simultaneously. Selker and colleagues propose a continuum that creates a smooth
      transition from controlled experiments to real-world, real-time studies within a
      single mechanism. 

PMID- 24448459
TI  - In vitro prediction of clinical drug interactions with CYP3A substrates: we are
      not there yet.
AB  - In 1973, Malcolm Rowland and associates described an approach to predicting
      clinical pharmacokinetic drug-drug interactions (DDIs) using an inhibition
      constant determined in vitro (Ki) together with anticipated inhibitor exposure in
      vivo ([I]). Despite numerous modifications and refinements of the core model over
      the following 40 years, we still have not achieved a predictive paradigm having
      accuracy sufficient to justify bypassing all, or even most, clinical DDI studies
      in the course of drug development. 

PMID- 24448460
TI  - Methylphenidate treatment in children with attention deficit hyperactivity
      disorder and comorbid social phobia.
AB  - The aim of this study was to assess the response of social phobia (SP) symptoms
      to methylphenidate (MPH) treatment in children with attention deficit
      hyperactivity disorder (ADHD). Twenty-one ADHD patients with SP, aged between 8
      and 18 years, received 12 weeks of MPH treatment. The severity of SP symptoms
      were assessed by the Liebowitz Social Anxiety Scale for Children and Adolescents
      (LSAS-CA), and the severity of ADHD symptoms was assessed by the ADHD Rating
      Scale at baseline and at endpoint. MPH treatment was associated with a
      significant decrease in the ADHD Rating Scale scores (P<0.0001) and in the total
      LSAS-CA scores (P=0.013), as well as the school-related items of LSAS-CA
      (P=0.011). A significant correlation was found between the reductions in ADHD
      score and total LSAS-CA score (P=0.038), especially in school-related SP. The
      improvement in ADHD symptoms because of MPH treatment correlates with a parallel
      improvement in SP. MPH treatment appears to be safe and effective in ADHD/SP
      children. 

PMID- 24448461
TI  - Occurrence and spatial distribution of microplastics in sediments from Norderney.
AB  - The spatial distribution of small potential microplastics (SPM) (<1 mm) in beach
      sediments was studied on a 500 m stretch of the North Sea island of Norderney.
      Their correlation with visible plastic debris (VPD) (>1 mm) was also examined.
      Small microparticles were extracted from 36 one kg sediment samples and analysed
      by visual microscopic inspection and partly by thermal desorption pyrolysis gas
      chromatography/mass spectrometry. The smallest particle size that could be
      analysed with this method was estimated to be 100 MUm. The mean number of SPM at
      the three sampling sites (n = 12) was 1.7, 1.3 and 2.3 particles per kg dry
      sediment, respectively. SPM were identified as polypropylene, polyethylene,
      polyethylene terephthalate, polyvinylchloride, polystyrene and polyamide. The
      organic plastic additives found were benzophenone, 1,2-benzenedicarboxylic acid,
      dimethyl phthalate, diethylhexyl phthalate, dibutyl phthalate, diethyl phthalate,
      phenol and 2,4-di-tert-butylphenol. Particles were distributed rather
      homogenously and the occurrence of SPM did not correlate with that of VPD.

PMID- 24448462
TI  - Alkyne aminohalogenation enabled by DBU-activated N-haloimides: direct synthesis
      of halogenated enamines.
AB  - Activated by DBU, N-haloimides can be used as both halogen and nitrogen sources
      to achieve the difunctionalization of terminal alkynes, giving rise to useful
      halogenated enamines with high efficiency and high regio- and
      stereoselectivities. The cascade reaction features simple manipulation, mild
      conditions, a broad substrate scope, readily available reagents, and atom
      economy. 

PMID- 24448463
TI  - Time to revisit product placement in films and on television to promote health
      damaging products.

PMID- 24448464
TI  - Production of hydrogen by electrocatalysis: making the H-H bond by combining
      protons and hydrides.
AB  - Generation of hydrogen by reduction of two protons by two electrons can be
      catalysed by molecular electrocatalysts. Determination of the thermodynamic
      driving force for elimination of H2 from molecular complexes is important for the
      rational design of molecular electrocatalysts, and allows the design of metal
      complexes of abundant, inexpensive metals rather than precious metals ("Cheap
      Metals for Noble Tasks"). The rate of H2 evolution can be dramatically
      accelerated by incorporating pendant amines into diphosphine ligands. These
      pendant amines in the second coordination sphere function as protons relays,
      accelerating intramolecular and intermolecular proton transfer reactions. The
      thermodynamics of hydride transfer from metal hydrides and the acidity of
      protonated pendant amines (pK(a) of N-H) contribute to the thermodynamics of
      elimination of H2; both of the hydricity and acidity can be systematically varied
      by changing the substituents on the ligands. A series of Ni(II) electrocatalysts
      with pendant amines have been developed. In addition to the thermochemical
      considerations, the catalytic rate is strongly influenced by the ability to
      deliver protons to the correct location of the pendant amine. Protonation of the
      amine endo to the metal leads to the N-H being positioned appropriately to favor
      rapid heterocoupling with the M-H. Designing ligands that include proton relays
      that are properly positioned and thermodynamically tuned is a key principle for
      molecular electrocatalysts for H2 production as well as for other multi-proton,
      multi-electron reactions important for energy conversions.

PMID- 24448465
TI  - Genotoxic effects of the herbicide Roundup Transorb and its active ingredient
      glyphosate on the fish Prochilodus lineatus.
AB  - Roundup Transorb (RT) is a glyphosate-based herbicide and despite its wide use
      around the world there are few studies comparing the effects of the active
      ingredient with the formulated product. In this context the purpose of this study
      was to compare the genotoxicity of the active ingredient glyphosate with the
      formulated product RT in order to clarify whether the active ingredient and the
      surfactant of the RT formula may exert toxic effects on the DNA molecule in
      juveniles of fish Prochilodus lineatus. Erythrocytes and gill cells of fish
      exposed to glyphosate and to RT showed DNA damage scores significantly higher
      than control animals. These results revealed that both glyphosate itself and RT
      were genotoxic to gill cells and erythrocytes of P. lineatus, suggesting that
      their use should be carefully monitored considering their potential impact on
      tropical aquatic biota.

PMID- 24448466
TI  - Chronic unpredictable mild stress impairs erythrocyte immune function and changes
      T-lymphocyte subsets in a rat model of stress-induced depression.
AB  - Stress has been shown to suppress immune function and increase susceptibility to
      inflammatory and psychiatric diseases. This study sought to investigate the
      changes in erythrocyte immune functions and T-lymphocyte subsets and to explore
      the mechanism implicated in the process of stress-induced depression by employing
      a rat depression model induced by chronic unpredictable mild stress (CUMS). The
      body weights and behavioral changes of the rats were recorded, and plasma
      corticosterone levels were determined by radioimmunoassay. Erythrocyte immune
      function and T-lymphocytes subsets were respectively measured by the method of
      yeast rosette and flow cytometry at different time intervals, and their
      relationship was analyzed. Results indicated that a reduction was observed in the
      following: the rats' crossing and rearing movement times, the volume of sucrose
      intake and the preference for sucrose in the depression model group. Plasma
      corticosterone levels were elevated; the rate of E-C3bR decreased, and E-IC was
      increased. Some alterations in the percentage of T-lymphocytes and IL-2 appeared
      in the depression model group and some relationships existed between these
      parameters. Collectively, these findings disclose that long-time stress could
      induce changes in rat behavior and activities through an effect on erythrocyte
      immune functions and T-lymphocyte subsets. 

PMID- 24448467
TI  - Arsenic reduces the antipyretic activity of paracetamol in rats: modulation of
      brain COX-2 activity and CB1 receptor expression.
AB  - We examined whether subacute arsenic exposure can reduce paracetamol-mediated
      antipyretic activity by affecting COX pathway and cannabinoid CB1 receptor
      regulation. Rats were preexposed to elemental arsenic (4 ppm) as sodium arsenite
      through drinking water for 28 days. Next day pyrexia was induced with
      lipopolysaccharide and paracetamol's (200 mg/kg, oral) antipyretic activity was
      assessed. The activities of COX-1 and COX-2, the levels of PGE2, TNF-alpha and IL
      1beta and expression of CB1 receptors were assessed in brain. Arsenic inhibited
      paracetamol-mediated antipyretic activity. COX-1 activity was not affected by any
      treatments. Paracetamol decreased COX-2 activity, levels of PGE2, TNF-alpha and
      IL-1beta and caused up-regulation of CB1 receptors. Arsenic caused opposite
      effects on these parameters. In the arsenic-preexposed rats, paracetamol-mediated
      effects were attenuated, while CB1 receptor up-regulation was reversed to down
      regulation. Results suggest that elevated COX-2 activity and reduced CB1
      expression could be involved in the arsenic-mediated attenuation of the
      antipyretic activity of paracetamol.

PMID- 24448469
TI  - Network-level accident-mapping: Distance based pattern matching using artificial
      neural network.
AB  - The objective of an accident-mapping algorithm is to snap traffic accidents onto
      the correct road segments. Assigning accidents onto the correct segments
      facilitate to robustly carry out some key analyses in accident research including
      the identification of accident hot-spots, network-level risk mapping and segment
      level accident risk modelling. Existing risk mapping algorithms have some severe
      limitations: (i) they are not easily 'transferable' as the algorithms are
      specific to given accident datasets; (ii) they do not perform well in all road
      network environments such as in areas of dense road network; and (iii) the
      methods used do not perform well in addressing inaccuracies inherent in and type
      of road environment. The purpose of this paper is to develop a new accident
      mapping algorithm based on the common variables observed in most accident
      databases (e.g. road name and type, direction of vehicle movement before the
      accident and recorded accident location). The challenges here are to: (i) develop
      a method that takes into account uncertainties inherent to the recorded traffic
      accident data and the underlying digital road network data, (ii) accurately
      determine the type and proportion of inaccuracies, and (iii) develop a robust
      algorithm that can be adapted for any accident set and road network of varying
      complexity. In order to overcome these challenges, a distance based pattern
      matching approach is used to identify the correct road segment. This is based on
      vectors containing feature values that are common in the accident data and the
      network data. Since each feature does not contribute equally towards the
      identification of the correct road segments, an ANN approach using the single
      layer perceptron is used to assist in "learning" the relative importance of each
      feature in the distance calculation and hence the correct link identification.
      The performance of the developed algorithm was evaluated based on a reference
      accident dataset from the UK confirming that the accuracy is much better than
      other methods. 

PMID- 24448468
TI  - LZTS1 downregulation confers paclitaxel resistance and is associated with worse
      prognosis in breast cancer.
AB  - The Leucine Zipper Tumor Suppressor 1 (LZTS1) is a tumor suppressor gene, located
      at chromosome 8p22, which is frequently altered in human cancer. In normal
      tissue, its ubiquitous expression regulates cell mitosis by the stabilization of
      microtubule networks. LZTS1-deficient mouse embryonic fibroblasts have been shown
      to have an accelerated mitotic progression, and a higher resistance to taxanes,
      microtubule-stabilizing drugs. We investigate the role of Lzts1 in paclitaxel
      resistance in breast cancer cells. Downregulation of Lzts1 expression
      significantly decreases sensitivity to paclitaxel in vitro. We further analyzed
      Lzts1 expression by immunohistochemistry in 270 primary breast cancer samples and
      16 normal breast specimens. Lzts1 was significantly downregulated in breast
      cancer samples and its deregulation was associated with a higher incidence of
      tumor recurrence, and to a worse overall survival. Moreover, Lzts1-negative
      tumors were associated with unfavorable outcome after taxanes-based therapy. Thus
      our data suggest that Lzts1 deregulation is involved in breast cancer and its
      immunohistochemical evaluation may serve as a prognostic factor for breast cancer
      therapy.

PMID- 24448470
TI  - Alcohol consumption, helmet use and head trauma in cycling collisions in Germany.
AB  - Cycling, being easy, inexpensive and healthy, is becoming one of the most popular
      means of transport. Cyclists, however, are among the most vulnerable road users
      in traffic collisions. The aims of this study were to establish which cyclist and
      cycling accident characteristics are associated with alcohol consumption and
      helmet use in Germany and to identify risk factors related to head trauma
      sustained in cycling accidents. The source used for the present analysis was the
      database of the German in-depth accident study (GIDAS). All cyclists who had been
      involved in a road accident between 2000 and 2010 and submitted to an alcohol
      test were selected. Logistic regression analyses were carried out to evaluate
      various aspects: alcohol consumption, helmet use, head trauma, and
      cyclist/accident characteristics. Female riders were less likely to have consumed
      alcohol (OR=0.23, 95% CI: 0.08-0.66); cyclists who did not wear a helmet were
      more likely to have consumed alcohol (OR=2.41, 95% CI: 1.08-5.38); cyclists who
      were not responsible for the collision were less likely to have consumed alcohol
      than those who were partially responsible for the accident (OR=0.22, 95% CI: 0.08
      0.61). Cyclists involved in collisions with another vehicle, motorised or not,
      had a lower risk of suffering a head injury compared with those involved in
      single-vehicle accidents (OR=0.27, 95% CI: 0.12-0.62, and OR=0.08, 95% CI: 0.03
      0.22, respectively). The prevention or limiting of alcohol consumption among
      cyclists and the corresponding testing of cyclists must be improved. Training
      initiatives on helmet protection should be encouraged. 

PMID- 24448471
TI  - Bicyclist safety performance functions for a U.S. city.
AB  - Efforts have intensified to apply a more evidence-based approach to traffic
      safety. One such effort is the Highway Safety Manual, which provides typical
      safety performance functions (SPFs) for common road types. SPFs model the
      mathematical relationship between frequency of crashes and the most significant
      causal factors. Unfortunately, the manual provides no SPFs for bicyclists,
      despite disproportionately high fatalities among this group. In this paper, a
      method for creating city-specific, bicycle SPFs is presented and applied to
      Boulder, Colorado. This is the first time a bicycle SPF has been created for a
      U.S. city. Such functions provide a basis for both future investigations into
      safety treatment efficacy and for prioritizing intersections to better allocate
      scarce funds for bicycle safety improvements. As expected, the SPFs show that
      intersections with higher bicyclist traffic and higher motorist traffic have
      higher motorist-cyclist collisions. The SPFs also demonstrate that intersections
      with more cyclists have fewer collisions per cyclist, illustrating that cyclists
      are safer in numbers. Intersections with fewer than 200 entering cyclists have
      substantially more collisions per cyclist. 

PMID- 24448472
TI  - A diffuse intrinsic pontine glioma in a neonate diagnosed by MRI.

PMID- 24448473
TI  - Functional genomics of cardiovascular development and disease.

PMID- 24448474
TI  - The biotechnology innovation machine: a source of intelligent biopharmaceuticals
      for the pharma industry--mapping biotechnology's success.
AB  - The marriage of biotechnology and the pharmaceutical industry (pharma) is
      predicated on an evolution in technology and product innovation. It has come as a
      result of advances in both the science and the business practices of the
      biotechnology sector in the past 30 years. Biotechnology products can be thought
      of as "intelligent pharmaceuticals," in that they often provide novel mechanisms
      of action, new approaches to disease control, higher clinical success rates,
      improved patient care, extended patent protection, and a significant likelihood
      of reimbursement. Although the first biotechnology product, insulin, was approved
      just 32 years ago in 1982, today there are more than 200 biotechnology products
      commercially available. Research has expanded to include more than 900
      biotechnology products in clinical trials. Pharma is substantially engaged in
      both the clinical development of these products and their commercialization. 

PMID- 24448475
TI  - Pharmacogenetics in the cancer clinic: from candidate gene studies to next
      generation sequencing.
AB  - Genetics has significantly added to our understanding of variability in drug
      response, especially in cancer treatment. Pharmacogenetics, aimed at predicting a
      patient's chance for effective and safe drug treatment by interrogating germ line
      genetic variants, has moved from investigating a monogenetic candidate gene to
      examining complex phenotype-based genome-wide approaches. With the rapid advances
      in sequencing technologies, decline in costs, and swift turnaround times, large
      scale genomic information will become available in the clinical setting,
      facilitating implementation of pharmacogenetics. 

PMID- 24448476
TI  - Exploring the FDA adverse event reporting system to generate hypotheses for
      monitoring of disease characteristics.
AB  - The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS)
      is a database for postmarketing drug safety monitoring and influences changes in
      FDA safety guidance documents such as drug labels. The number of cases in the
      FAERS has rapidly increased with the improvement of submission methods and data
      standards and thus has become an important resource for regulatory science.
      Although the FAERS has been predominantly used for safety signal detection, this
      study explored its utility for disease characteristics. 

PMID- 24448477
TI  - Phase-transition-driven growth of compound semiconductor crystals from ordered
      metastable nanorods.
AB  - In polycrystalline semiconductors, grain boundaries are often sites with
      prevalence for electron-hole recombination and various strategies have been
      followed to minimize grain boundary areas. Generally, large grains or epitaxial
      films can be obtained at high temperatures. However, high growth temperatures
      limit the choice of substrate materials and can prove elusive for semiconductors
      comprising volatile elements such as kesterite Cu2ZnSnS4. Here we show that this
      limitation can be overcome by a transition of a matrix of densely packed
      metastable nanorods into large stable grains. Real-time analysis reveals that the
      grain growth is driven by a direct, isocompositional solid-state phase
      transition. Following this route, semiconductor films with a large-grained
      microstructure can be achieved within a few seconds at relatively low
      temperatures. Grain size as well as electrical and optical properties of the
      resulting films can be controlled via the heating rate. This synthesis route
      opens new possibilities for the fabrication of semiconductor crystals for
      photoelectric devices with tailored microstructures. 

PMID- 24448478
TI  - Pencil drawn strain gauges and chemiresistors on paper.
AB  - Pencil traces drawn on print papers are shown to function as strain gauges and
      chemiresistors. Regular graphite/clay pencils can leave traces composed of
      percolated networks of fine graphite powders, which exhibit reversible resistance
      changes upon compressive or tensile deflections. Flexible toy pencils can leave
      traces that are essentially thin films of graphite/polymer composites, which show
      reversible changes in resistance upon exposure to volatile organic compounds due
      to absorption/desorption induced swelling/recovery of the polymer binders. Pencil
      on-paper devices are low-cost, extremely simple and rapid to fabricate. They are
      light, flexible, portable, disposable, and do not generate potentially negative
      environmental impact during processing and device fabrication. One can envision
      many other types of pencil drawn paper electronic devices that can take on a
      great variety of form factors. Hand drawn devices could be useful in resource
      limited or emergency situations. They could also lead to new applications
      integrating art and electronics. 

PMID- 24448479
TI  - The scope of the conscience-based exemption in Section 4(1) of the Abortion Act
      1967: Doogan and Wood v NHS Greater Glasgow Health Board [2013] CSIH 36.
AB  - Doogan is a judgment of the Inner House of the Scottish Court of Session in an
      action brought by two midwives ('petitioners' at first instance and 'reclaimers'
      on appeal) for judicial review of a decision by Greater Glasgow and Clyde Health
      Board ('respondents'). At issue in the litigation was the scope of the conscience
      based exemption contained in section 4(1) of the Abortion Act 1967, which
      included consideration of where the burden of managing the exemption should fall.
      The court of first instance (Outer House) had held that section 4(1), which
      exempts people with a conscientious objection from having to 'participate in any
      treatment authorised by this Act', ought to be read in light of section 1, which
      was the authorising provision. On the analysis adopted by the Outer House, any
      activity which was not unlawful before the 1967 Act came into force, and which
      therefore did not require to be authorised by section 1, was not covered by
      section 4(1). Roles which consisted of 'supervision, delegation, and support'
      were held not to fall within the scope of section 4(1) for this reason. The Inner
      House rejected the argument that the scope of the exemption in section 4(1) must
      be coextensive with the scope of the authorisation in section 1, and held that
      section 4(1) covered the 'whole process of treatment' given for the purpose of
      terminating a pregnancy. For the Inner House, therefore, 'supervision,
      delegation, and support' of staff directly involved in the abortion process did
      constitute the kind of 'participation' that a person could be exempted from under
      section 4(1). Moreover, the court took the view that the reclaimers'
      interpretation of section 4(1) was also to be preferred in terms of its likely
      management consequences. The appeal succeeded, and the Health Board has begun the
      process of appealing to the UK Supreme Court. 

PMID- 24448481
TI  - Significance of measurements of peripheral carbonyl stress markers in a cross
      sectional and longitudinal study in patients with acute-stage schizophrenia.
AB  - Altered peripheral carbonyl stress markers, high levels of serum pentosidine,
      which accumulates following carbonyl stress, and low levels of pyridoxal (vitamin
      B6), which detoxifies reactive carbonyl compounds, have been reported in a cross
      sectional study of chronic schizophrenia. However, changes in the levels of these
      compounds in patients with schizophrenia have not been investigated in a
      longitudinal study. To clarify whether these markers may be biological markers
      that reflect the clinical course of the disease, the serum levels of these
      compounds were investigated in a cross-sectional and a longitudinal study. One
      hundred and thirty-seven acute-stage Japanese patients were enrolled. Among
      these, 53 patients were followed from the acute stage to remission. A portion of
      patients in the acute stage (14 cases, 10.2%) showed extremely high pentosidine
      levels. These levels were not associated with the severity of symptoms but were
      associated with antipsychotic dose amounts. Pyridoxal levels were lower in
      schizophrenia and increased according to the clinical course of the illness.
      Furthermore, 18 patients with decreased pyridoxal levels according to the
      clinical course showed that the greater the decrease in pyridoxal levels, the
      lesser the improvement in symptoms. Thus, extremely high pentosidine levels in a
      portion of patients may be caused by higher daily antipsychotic doses, whereas
      pyridoxal levels were lower in schizophrenia and increased according to the
      clinical course. Patients with decreasing pyridoxal levels during the clinical
      course showed less improvement in symptoms. Carbonyl stress markers may also be
      therapeutic biological markers in some patients with schizophrenia. 

PMID- 24448480
TI  - Label-free mass spectrometry exploits dozens of detected peptides to quantify
      lamins in wildtype and knockdown cells.
AB  - Label-free quantitation and characterization of proteins by mass spectrometry
      (MS) is now feasible, especially for moderately expressed structural proteins
      such as lamins that typically yield dozens of tryptic peptides from tissue cells.
      Using standard cell culture samples, we describe general algorithms for
      quantitative analysis of peptides identified in liquid chromatography tandem mass
      spectrometry (LC-MS/MS). The algorithms were foundational to the discovery that
      the absolute stoichiometry of A-type to B-type lamins scales with tissue
      stiffness (Swift et al., Science 2013). Isoform dominance helps make sense of why
      mutations and changes with age of mechanosensitive lamin-A,C only affect "stiff"
      tissues such as heart, muscle, bone, or even fat, but not brain. A Peak Ratio
      Fingerprinting (PRF) algorithm is elaborated here through its application to
      lamin-A,C knockdown. After demonstrating the large dynamic range of PRF using
      calibrated mixtures of human and mouse lysates, we validate measurements of
      partial knockdown with standard cell biology analyses using quantitative
      immunofluorescence and immunoblotting. Optimal sets of MS-detected peptides as
      determined by PRF demonstrate that the strongest peptide signals are not
      necessarily the most reliable for quantitation. After lamin-A,C knockdown, PRF
      computes an invariant set of "housekeeping" proteins as part of a broader
      proteomic analysis that also shows the proteome of mesenchymal stem cells (MSCs)
      is more broadly perturbed than that of a human epithelial cancer line (A549s),
      with particular variation in nuclear and cytoskeletal proteins. These methods
      offer exciting prospects for basic and clinical studies of lamin-A,C as well as
      other MS-detectable proteins. 

PMID- 24448482
TI  - Modeled subalpine plant community response to climate change and atmospheric
      nitrogen deposition in Rocky Mountain National Park, USA.
AB  - To evaluate potential long-term effects of climate change and atmospheric
      nitrogen (N) deposition on subalpine ecosystems, the coupled biogeochemical and
      vegetation community competition model ForSAFE-Veg was applied to a site at the
      Loch Vale watershed of Rocky Mountain National Park, Colorado. Changes in climate
      and N deposition since 1900 resulted in pronounced changes in simulated plant
      species cover as compared with ambient and estimated future community
      composition. The estimated critical load (CL) of N deposition to protect against
      an average future (2010-2100) change in biodiversity of 10% was between 1.9 and
      3.5 kg N ha(-1) yr(-1). Results suggest that the CL has been exceeded and
      vegetation at the study site has already undergone a change of more than 10% as a
      result of N deposition. Future increases in air temperature are forecast to cause
      further changes in plant community composition, exacerbating changes in response
      to N deposition alone. 

PMID- 24448483
TI  - Components from wheat roots modify the bioactivity of ZnO and CuO nanoparticles
      in a soil bacterium.
AB  - ZnO and CuO nanoparticles (NPs) have widespread commercial uses and their impact
      on agricultural systems is unresolved. This study examined whether the
      metabolites washed from wheat (Triticum aestivum L.) roots modulated the
      metabolic response to the NPs of a biosensor generated in the root colonizer,
      Pseudomonas putida KT2440. The root wash components boosted light output of the
      biosensor consistent with their catabolism. Dose-dependent and rapid inhibition
      of cell metabolism occurred with both ZnO and CuO NPs in water suspensions but
      high light output was maintained in root wash. Root wash also protected biosensor
      output in challenges with Zn ions. However the root wash components did not
      protect culturability or biosensor light output upon exposure to Cu ions. Imaging
      by atomic force microscopy suggested that root wash materials coated the NPs. We
      deduced that the response of a microbe to these metal oxide NPs could be negated
      by components released from roots. 

PMID- 24448484
TI  - Separation of motile bacteria using drift velocity in a microchannel.
AB  - Separation of certain bacteria from liquids is important in the food, water
      quality management, bioengineering, and pharmaceutical industries. In this study,
      we developed a microfluidic device for the hydrodynamic separation of motile
      bacteria (Escherichia coli) using drift velocity. We first investigated drift
      tendencies of bacteria and found that cells tended to move in a spanwise
      direction with similar velocities regardless of the flow rate. When the drift
      distance was small compared to the wetted perimeter of the cross section, the
      cells were not separated efficiently. We then investigated the drift phenomenon
      in more detail using a numerical simulation. Interestingly, the drift phenomenon
      was observed even without a wall boundary, indicating that drift was caused
      mainly by the interaction of moving cells with the background shear flow.
      Finally, we developed a microfluidic device to separate motile bacteria from
      tracer particles or less motile cells. By decreasing the channel height, the
      device could successfully separate motile bacteria from other particles or cells
      with a separation efficiency of about 40%. Connecting microchannels in a series
      was also found to be effective, which achieved the separation efficiency of about
      60%. The knowledge obtained in this study will facilitate the development of
      other microfluidics devices for use with bacteria. 

PMID- 24448485
TI  - Trench foot: a relatively rare condition in tropical countries - a case report.
AB  - Trench foot is a relatively rare condition in tropical countries. We present here
      a case report of trench foot in a child who was put on hip spica for her hip
      ailment. Although rare, awareness on the part of the clinician can prevent this
      potentially serious condition and early diagnosis and treatment can prevent
      further consequences. 

PMID- 24448486
TI  - Induction of Candida albicans biofilm formation on silver-coated vascular grafts.
AB  - OBJECTIVES: Silver exhibits excellent antimicrobial properties and is used to
      protect medical devices from microbial colonization. Because few data are
      available on the influence of silver coating of vascular prostheses on Candida
      biofilm formation, this study aimed to investigate the effect of silver on yeast
      biofilm formation in an in vitro model. METHODS: Prosthesis material was co
      cultivated with two different strains of Candida albicans and the effect of
      silver on attachment and the growth of biofilms was monitored by microscopy and
      by quantification of cfu and mitochondrial dehydrogenase activity. RESULTS:
      Silver collagen-coated vascular prostheses significantly reduced C. albicans
      biofilm formation in serum-free medium. Paradoxically, in the presence of 50%
      serum, silver increased the growth of biofilms on silver-containing prostheses 2-
      to 10-fold compared with silver-free prostheses. Silver ion concentrations
      between 1.7 and 0.17 mg/L, corresponding roughly to 1/20 to 1/200 of the MIC of
      silver nitrate, stimulated biofilm formation by C. albicans. CONCLUSIONS: Serum
      proteins reduced the concentration of silver ions delivered from the surface of
      vascular prostheses to a subinhibitory level, which stimulated the attachment and
      biofilm formation of C. albicans on grafts. Silver collagen coating therefore
      seems to be unsuitable for the prevention of growth of C. albicans on vascular
      prostheses under physiological conditions.

PMID- 24448487
TI  - Virological escape in HCV genotype-1-infected patients receiving daclatasvir plus
      ribavirin and peginterferon alfa-2a or alfa-2b.
AB  - BACKGROUND: Daclatasvir (DCV; BMS-790052) is a picomolar inhibitor of HCV non
      structural protein 5A (NS5A) and has demonstrated efficacy in patients
      chronically infected with HCV. METHODS: In the double-blind, randomized studies
      AI444021 and AI444022, 71 Japanese patients chronically infected with HCV
      genotype 1 (predominantly genotype 1b) received DCV (10 mg or 60 mg) plus
      peginterferon alfa-2b or alfa-2a and ribavirin. Virological failure occurred in
      14% (5/36) of treatment-naive patients and 54% (19/35) of prior alfa/ribavirin
      non-responders. Resistance testing was performed on baseline samples and samples
      with HCV RNA>=1,000 IU/ml at week 1 through post-treatment week 24. RESULTS:
      Baseline NS5A resistance-associated polymorphisms had less impact on virological
      response rates than IL28B genotype. All patients with virological failure had
      NS5A DCV-resistant variants at the time of failure. The predominant NS5A variants
      were L31V/M/I plus Y93H; this combination was detected in 100% (5/5) of treatment
      naive patients and 74% (14/19) of non-responders with failure. Emergent
      resistance variants in prior non-responders (four viral breakthroughs, one
      relapse) were more varied with novel combinations such as L31F-DeltaP32 and L28M
      R30Q-A92K detected. Significant loss in DCV antiviral activity was generally only
      seen with >= two resistance-associated NS5A substitutions. All DCV-resistant
      variants were still detected at end of study. CONCLUSIONS: Virological failure in
      HCV genotype 1b treatment-naive Japanese patients receiving DCV plus alfa
      2a/ribavirin or alfa-2b/ribavirin was associated with enrichment of NS5A
      resistance variants L31V/M-Y93H. In prior non-responders, emergent variants
      associated with failure also included NS5A-A92K or NS5A-DeltaP32. As with L31-Y93
      variants, these variants persisted.

PMID- 24448488
TI  - Is mind-mindedness trait-like or a quality of close relationships? Evidence from
      descriptions of significant others, famous people, and works of art.
AB  - The four studies reported here sought to explore the nature of the construct of
      mind-mindedness. In Study 1, involving 37 mothers of 5- to 8-year-old children,
      mothers' verbal mind-minded descriptions of their children were positively
      correlated with their mind-minded descriptions of their current romantic partner.
      Participants in Studies 2 (N=114), 3 (N=173), and 4 (N=153) were young adults who
      provided written descriptions of: a close friend and their current romantic
      partner (Study 2); two specified famous people, two works of art, and a close
      friend (Study 3); a specified famous person, a famous person of the participant's
      choice, and a close friend (Study 4). Study 2 obtained paper-and-pen written
      descriptions, whereas participants completed descriptions in electronic format in
      Studies 3 and 4. Mind-minded descriptions of friends and partners were positively
      correlated, but there was no relation between mind-minded descriptions of a
      friend and the tendency to describe famous people or works of art in mind-minded
      terms. Levels of mind-mindedness were higher in descriptions of friends compared
      with descriptions of famous people or works of art. Administration format was
      unrelated to individuals' mind-mindedness scores. The results suggest that mind
      mindedness is a facet of personal relationships rather than a trait-like quality.

PMID- 24448489
TI  - Prostaglandin E2 promotes post-infarction cardiomyocyte replenishment by
      endogenous stem cells.
AB  - Although self-renewal ability of adult mammalian heart has been reported, few
      pharmacological treatments are known to promote cardiomyocyte regeneration after
      injury. In this study, we demonstrate that the critical period of stem/progenitor
      cell-mediated cardiomyocyte replenishment is initiated within 7 days and
      saturates on day 10 post-infarction. Moreover, blocking the inflammatory reaction
      with COX-2 inhibitors may also reduce the capability of endogenous
      stem/progenitor cells to repopulate lost cells. Injection of the COX-2 product
      PGE2 enhances cardiomyocyte replenishment in young mice and recovers cell renewal
      through attenuating TGF-beta1 signaling in aged mice. Further analyses suggest
      that cardiac stem cells are PGE2-responsive and that PGE2 may regulate stem cell
      activity directly through the EP2 receptor or indirectly by modulating its micro
      environment in vivo. Our findings provide evidence that PGE2 holds great
      potential for cardiac regeneration. 

PMID- 24448490
TI  - VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia
      resistance in the heart.
AB  - Angiogenic growth factors have recently been linked to tissue metabolism. We have
      used genetic gain- and loss-of function models to elucidate the effects and
      mechanisms of action of vascular endothelial growth factor-B (VEGF-B) in the
      heart. A cardiomyocyte-specific VEGF-B transgene induced an expanded coronary
      arterial tree and reprogramming of cardiomyocyte metabolism. This was associated
      with protection against myocardial infarction and preservation of mitochondrial
      complex I function upon ischemia-reperfusion. VEGF-B increased VEGF signals via
      VEGF receptor-2 to activate Erk1/2, which resulted in vascular growth. Akt and
      mTORC1 pathways were upregulated and AMPK downregulated, readjusting
      cardiomyocyte metabolic pathways to favor glucose oxidation and macromolecular
      biosynthesis. However, contrasting with a previous theory, there was no
      difference in fatty acid uptake by the heart between the VEGF-B transgenic, gene
      targeted or wildtype rats. Importantly, we also show that VEGF-B expression is
      reduced in human heart disease. Our data indicate that VEGF-B could be used to
      increase the coronary vasculature and to reprogram myocardial metabolism to
      improve cardiac function in ischemic heart disease. 

PMID- 24448491
TI  - Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a
      Niemann Pick disease type A mouse model.
AB  - Understanding the role of lipids in synapses and the aberrant molecular
      mechanisms causing the cognitive deficits that characterize most lipidosis is
      necessary to develop therapies for these diseases. Here we describe sphingomyelin
      (SM) as a key modulator of the dendritic spine actin cytoskeleton. We show that
      increased SM levels in neurons of acid sphingomyelinase knock out mice (ASMko),
      which mimic Niemann Pick disease type A (NPA), result in reduced spine number and
      size and low levels of filamentous actin. Mechanistically, SM accumulation
      decreases the levels of metabotropic glutamate receptors type I (mGluR1/5) at the
      synaptic membrane impairing membrane attachment and activity of RhoA and its
      effectors ROCK and ProfilinIIa. Pharmacological enhancement of the neutral
      sphingomyelinase rescues the aberrant molecular and morphological phenotypes in
      vitro and in vivo and improves motor and memory deficits in ASMko mice.
      Altogether, these data demonstrate the influence of SM and its catabolic enzymes
      in dendritic spine physiology and contribute to our understanding of the
      cognitive deficits of NPA patients, opening new perspectives for therapeutic
      interventions. 

PMID- 24448492
TI  - Imbalance of folic acid and vitamin B12 is associated with birth outcome: an
      Indian pregnant women study.
AB  - BACKGROUND/OBJECTIVES: Maternal nutrient supplementation in developing countries
      is generally restricted to provision of iron and folic acid. Along with folic
      acid, vitamin B12 is also an important determinant of fetal growth and
      development. During pregnancy, the increased requirement of folic acid is met
      with supplementation, while vitamin B12 remains untreated and possibly deficient.
      The objective of our study was to study the combined effect of maternal plasma
      folate and vitamin B12, and their ratio on birth anthropometrics.
      SUBJECTS/METHODS: We carried out an observational study on 49 full-term pregnant
      women at KEM Hospital, Pune, India, during 2006-2008, and measured plasma folate,
      vitamin B12 and homocysteine in venous blood at 36 weeks of gestation. Neonatal
      anthropometrics (birth weight, length, head circumference, abdominal
      circumference, mid arm circumference, chest circumference, triceps skinfold and
      subscapular skinfold thickness) were measured within 24 h of birth. RESULTS:
      Maternal plasma folate and vitamin B12 were not correlated to neonatal
      anthropometrics. The combined association of folate and vitamin B12 expressed as
      folate to vitamin B12 ratio was correlated to the neonatal anthropometrics.
      Imbalance in the maternal micronutrients with increasing ratio of folate to
      vitamin B12 was associated with an increase in plasma homocysteine (P=0.014),
      lowering of neonatal birth weight (P=0.009), birth length (P=0.034), head
      circumference (P=0.018) and chest circumference (P=0.009), while no significant
      association to other anthropometrics was observed. CONCLUSIONS: Supplementation
      of vitamin B12 in addition to supplementation of folic acid in pregnancy may be
      important for improving birth weight, birth length, head circumference and chest
      circumference.

PMID- 24448493
TI  - Re: Coffee consumption and risk of prostate cancer: an up-to-date meta-analysis.

PMID- 24448495
TI  - An anticancer drug to probe non-specific protein-DNA interactions.
AB  - A visible fluorescence switch of an eminent anti-carcinogen, ellipticine has been
      used to probe non-specific protein-DNA interaction. The unique pattern of protein
      DNA complexation is depicted for the first time through field emission scanning
      electron microscopy (FE-SEM) images and spectroscopic techniques. 

PMID- 24448496
TI  - Stable core-modified calixsmaragdyrins: synthesis, structure and specific sensing
      of the hydrogen sulfate ion.
AB  - Stable calixoxa- and calixthiasmaragdyrins containing three methine bridges and
      two direct bonds connecting the five pyrrole/heterocycle rings were synthesized
      by [3 + 2] condensation of dipyrromethane with 16-oxatripyrrane and 16
      thiatripyrrane respectively under mild acid-catalyzed conditions. The compounds
      were characterized by HR-MS, 1D & 2D NMR, absorption and electrochemical
      techniques and the structure of calixoxasmaragdyrin was solved by X-ray
      crystallography. The crystal structure analysis indicated that the
      calixoxasmaragdyrin macrocycle was highly distorted due to the flexibility
      introduced by one sp(3)meso-carbon. The compounds show ill-defined absorption
      bands and irreversible oxidation and reduction waves which were attributed to the
      disruption of conjugation of the macrocycle by incorporation of one sp(3)meso
      carbon. The anion binding studies indicated that the calixoxasmaragdyrin
      exhibited specific sensing ability for the HSO4(-) ion over other anions whereas
      calixthiasmaragdyrins did not even show an ability to bind anions. 

PMID- 24448494
TI  - Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis
      in the Diabetes Prevention Program.
AB  - BACKGROUND/OBJECTIVES: Low blood levels of 25-hydroxyvitamin D (25OHD) have been
      associated with cardiometabolic disease but results are inconsistent. The
      objective of the study was to investigate the association of 25OHD with metabolic
      syndrome in a population at increased risk for diabetes. SUBJECTS/METHODS: Using
      baseline data from the placebo and lifestyle intervention arms of the Diabetes
      Prevention Program (N=2000), multivariable logistic regression models were used
      to estimate the odds of prevalent metabolic syndrome and each of its individual
      components across 25OHD tertiles. Multivariable linear regression was used to
      estimate the adjusted mean difference of insulin secretion and sensitivity across
      the same 25OHD tertiles. In participants free of metabolic syndrome at baseline
      (N=546), incident metabolic syndrome in the first 2 years of follow-up was
      assessed using discrete-time proportional hazards regression to test its
      association with 25OHD concentration. RESULTS: After multivariate adjustment,
      participants in the highest tertile of 25OHD had lower odds of prevalent
      metabolic syndrome (odds ratio=0.62; 95% confidence interval (CI)=0.45-0.84),
      smaller waist circumference, higher high-density lipoprotein and lower fasting
      plasma glucose compared with participants in the lowest tertile of 25OHD. Higher
      plasma 25OHD concentration was associated with greater insulin sensitivity and
      lower insulin secretion. After multivariate adjustment, there was a
      nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD
      (hazard ratio=0.79; 95% CI=0.48-1.32) compared with the lowest tertile.
      CONCLUSIONS: In a population at increased risk for diabetes, higher plasma 25OHD
      concentration was inversely associated with prevalent metabolic syndrome and
      nonsignificantly with incident metabolic syndrome.

PMID- 24448497
TI  - Indian government gives green light to import frozen embryos.

PMID- 24448498
TI  - An automated integrated platform for rapid and sensitive multiplexed protein
      profiling using human saliva samples.
AB  - During the last decade, saliva has emerged as a potentially ideal diagnostic
      biofluid for noninvasive testing. In this paper, we present an automated,
      integrated platform useable by minimally trained personnel in the field for the
      diagnosis of respiratory diseases using human saliva as a sample specimen. In
      this platform, a saliva sample is loaded onto a disposable microfluidic chip
      containing all the necessary reagents and components required for saliva
      analysis. The chip is then inserted into the automated analyzer, the SDReader,
      where multiple potential protein biomarkers for respiratory diseases are measured
      simultaneously using a microsphere-based array via fluorescence sandwich
      immunoassays. The results are read optically, and the images are analyzed by a
      custom-designed algorithm. The fully automated assay requires as little as 10 MUL
      of saliva sample, and the results are reported in 70 min. The performance of the
      platform was characterized by testing protein standard solutions, and the results
      were comparable to those from the 3.5 h lab bench assay that we have previously
      reported. The device was also deployed in two clinical environments where 273
      human saliva samples collected from different subjects were successfully tested,
      demonstrating the device's potential to assist clinicians with the diagnosis of
      respiratory diseases by providing timely protein biomarker profiling information.
      This platform, which combines noninvasive sample collection and fully automated
      analysis, can also be utilized in point-of-care diagnostics. 

PMID- 24448499
TI  - Integrated analysis of germline and somatic variants in ovarian cancer.
AB  - We report the first large-scale exome-wide analysis of the combined germline
      somatic landscape in ovarian cancer. Here we analyse germline and somatic
      alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635
      high confidence, rare truncation and 22,953 missense variants with predicted
      functional impact. We find germline truncation variants and large deletions
      across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is
      shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation
      variants in genes not previously associated with ovarian cancer susceptibility
      (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in
      100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively.
      Germline-somatic interaction analysis combined with extensive bioinformatics
      annotation identifies 222 candidate functional germline truncation and missense
      variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants.
      Finally, integrated analyses of germline and somatic variants identify
      significantly altered pathways, including the Fanconi, MAPK and MLL pathways. 

PMID- 24448501
TI  - Diagnostic performance of multidetector computed tomography in the evaluation of
      perinephric fat invasion in renal cell carcinoma patients.
AB  - PURPOSE: This study aimed to evaluate the diagnostic performance of multidetector
      computed tomography (MDCT) for preoperative evaluation of perinephric fat
      invasion in patients with renal cell carcinomas (RCCs). METHODS: A total of 408
      consecutive patients with surgically confirmed RCC who underwent MDCT were
      included in this study. Image analysis was first performed with axial-only CT
      images. A second analysis was then performed with both axial and coronal CT
      images. A qualitative analysis was then conducted by 2 reviewers who reached
      consensus. The reference standard was pathologic evaluation. RESULTS: The areas
      under the curve of the receiver operating characteristic analysis were 0.786 and
      0.877 for axial-only images and 0.805 and 0.836 for combined images in both
      readers. The area under the curve of tumor size was 0.833, a similar value to
      that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or
      nodular type of fat infiltration, and an irregular tumor margin were independent
      predicting factors for perinephric fat invasion. CONCLUSIONS: The MDCT shows
      relatively high diagnostic performance in detecting perinephric fat invasion of
      RCC, but suffers from a relatively low positive predictive value. Tumor size, fat
      infiltration with a nodular appearance, and an irregular tumor margin were
      predictors for perinephric invasion.

PMID- 24448502
TI  - The use of bronchial arteries in the characterization of primary lung cancer: an
      MDCT study.
AB  - OBJECTIVE: The purpose of this study was to discuss the use of ipsilateral
      bronchial artery dilatation when a solitary lung mass is detected on
      multidetector computed tomography (MDCT). MATERIALS AND METHODS: We
      retrospectively evaluated 55 patients with solitary lung mass. An MDCT scanner
      was used for the study. Location and the greatest size of the tumor, and
      ipsilateral bronchial artery caliper (dilated if >2 mm) were noted for each
      patient. TNM staging of each patient with primary lung cancer was also recorded.
      Statistical analyses were applied to both groups using SPSS 17.0. chi test was
      used for the statistical analyses. RESULTS: Statistically strong correlation was
      observed between ipsilateral bronchial artery dilatation and primary lung
      carcinoma. Among the 11 benign lung masses, only 2 (18%) showed ipsilateral
      bronchial artery dilatation. But 39 (88.6%) of the 44 primary lung carcinoma
      patients and 36 (92.3%) of the 39 primary lung carcinoma patients with
      predominantly extramediastinal (lung) location showed ipsilateral bronchial
      artery dilatation on MDCT. When only predominantly extramediastinal lesions were
      taken into account, sensitivity of the study was 92.31%, specificity was 81.82%,
      positive predictive value was 94.74%, and negative predictive value was 75%.
      CONCLUSIONS: Lesion characterization and accuracy was very high when the only
      criteria of bronchial artery dilatation are taken into account. Sensitivity and
      negative predictive value were higher in the patients with extramediastinal
      lesions.

PMID- 24448503
TI  - Relationship of main pulmonary artery diameter to pulmonary arterial pressure in
      scleroderma patients with and without interstitial fibrosis.
AB  - OBJECTIVE: This study aimed to determine the relationship between main pulmonary
      artery diameter (MPAD) and pulmonary hypertension (PH) in scleroderma patients
      with and without interstitial lung disease. METHODS: We retrospectively reviewed
      48 subjects with scleroderma who underwent a chest computed tomography (CT) and
      right heart catheterization with 6 months of each other. Patients were divided
      into 2 groups based on the absence or presence of interstitial lung disease on
      chest CT. Subset analysis was performed based on available pulmonary function
      tests and divided into groups by forced vital capacity (FVC). Computed
      tomographic scans were scored for extent of fibrosis and ground glass opacity.
      Pulmonary artery and ascending aorta measurements were obtained by 2 independent
      observers. Univariate and multivariate models were used to evaluate the
      correlation between MPAD and mean pulmonary artery pressure (mPAP) measured by
      right heart catheterization. Receiver operating characteristic analysis was
      performed for diagnostic accuracy of the MPAD measurement in predicting PH.
      RESULTS: Strong correlations between mPAP and MPAD were found in this study
      regardless of the presence or absence of mild to moderate interstitial fibrosis
      on chest CT. When dividing patients based on FVC, the correlation between mPAP
      and MPAD was substantially attenuated. An MPAD value of 30.8 mm yielded the
      highest sensitivity and specificity at 81.3% and 87.5%, respectively.
      CONCLUSIONS: In scleroderma patients, an enlarged main pulmonary artery (>30 mm)
      predicts PH even in the presence of mild to moderate fibrosis although the
      relationship may be attenuated in the presence of a low % FVC.

PMID- 24448504
TI  - Patellofemoral friction syndrome: magnetic resonance imaging correlation of
      morphologic and T2 cartilage imaging.
AB  - OBJECTIVE: This study aimed to investigate whether patellofemoral T2 cartilage
      changes are associated with lateral patellofemoral friction syndrome (PFS), as
      indicated by an edema-like signal within the superolateral infrapatellar (Hoffa)
      fat pad. METHODS: In this institutional review board-approved retrospective study
      of 510 consecutive patients, 49 patients with 50 knee magnetic resonance imaging
      examinations demonstrating normal or low-grade patellofemoral cartilage
      abnormalities (whole-organ magnetic resonance imaging score [WORMS] score, <=2)
      were included. Twenty-two examinations with PFS (cases) were compared with an age
      and sex-matched cohort of 28 examinations without PFS (controls). A 3-T magnetic
      resonance imaging was performed with multi-echo, spin-echo T2 mapping. Two
      readers measured in consensus malalignment parameters, including patellar height
      index, tibial tuberosity to trochlear groove distance, and sulcus angle. Bulk T2
      cartilage values in the lateral and medial patellofemoral compartment, central
      weight-bearing medial and lateral femoral condyles were measured independently.
      Interobserver agreement was quantified using concordance correlation
      coefficients. Demographics, anatomic measurements, whole-organ magnetic resonance
      imaging scores, and cartilage T2 values were compared between cases and controls
      using Fisher exact test, Wilcoxon rank sum test, and mixed-effects models.
      RESULTS: Cases demonstrated higher patellar height index (P = 0.002) and tibial
      tuberosity to trochlear groove distance (P = 0.02). Interobserver agreement for
      T2 values was good overall (concordance correlation coefficient range, 0.65
      0.93). Cases demonstrated higher medial facet patellar bulk T2 (38.1 [7.5] ms)
      versus controls (33.6 [7.3] ms) (P = 0.02); otherwise, there were no significant
      differences in regional T2 values. CONCLUSIONS: T2 mapping in patients with PFS
      demonstrates increased cartilage T2 in the medial patellar facet, possibly
      reflecting collagen alteration from early chondromalacia (softening) or increased
      water content related to altered contact pressures.

PMID- 24448505
TI  - Prevalence and significance of perivascular soft tissue surrounding the hepatic
      artery after liver transplantation.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence and
      significance of perivascular soft tissue surrounding the hepatic artery on
      computed tomography (CT) after liver transplantation. MATERIALS AND METHODS: A
      total of 119 consecutive patients who underwent liver transplantation were
      retrospectively identified from a search of electronic medical records. Fourteen
      patients had histologic proof of posttransplant lymphoproliferative disease
      (PTLD). For each patient, the initial CT scan after transplantation, and the most
      recent CT scan if available, was analyzed for the presence of soft tissue in the
      porta hepatis region, particularly surrounding the transplanted hepatic artery.
      The hepatic artery was identified, and the maximum diameter of the soft tissue
      surrounding the vessel was measured and classified using the following scale:
      grade 0, none; grade 1, mild; grade 2, moderate; grade 3, moderate-large; and
      grade 4, large. RESULTS: Prevalence of perivascular soft tissue was 93% in the
      initial CT scans and follow-up studies. Comparing the initial and follow-up soft
      tissue measurements, 34% decreased, 62% were unchanged, and 4% increased. Using
      the Fisher exact test and a Mann-Whitney test, there was no statistically
      significant difference in the prevalence or diameter of perivascular soft tissue
      when comparing patients with pathologically proven PTLD and patients with no
      PTLD. Twenty-nine of the 119 patients underwent 68 positron emission
      tomography/CT scans in the time interval analyzed. Ninety percent of these
      patients had no abnormal fluorodeoxyglucose activity in the porta hepatis and
      portacaval regions. CONCLUSIONS: The presence of isolated perivascular soft
      tissue in patients after liver transplantation is a common finding and is not
      associated with lymphoproliferative disease.

PMID- 24448506
TI  - Evaluation of a near-infrared-type contrast medium extravasation detection system
      using a swine model.
AB  - PURPOSE: To refine the development and evaluate the near-infrared (NIR)
      extravasation detection system and its ability to detect extravasation during a
      contrast-enhanced computed tomography (CT) examination. MATERIALS AND METHODS:
      The NIR extravasation detection system projects the NIR light through the surface
      of the human skin then, using its sensory system, will monitor the changes in the
      amount of NIR that reflected, which varies based on absorption properties.Seven
      female pigs were used to evaluate the contrast media extravasation detection
      system, using a 20-gauge intravenous catheter, when injected at a rate of 1 mL/s
      into 4 different locations just under the skin in the thigh section. Using 3
      dimensional CT images, we evaluated the extravasations between time and volume,
      depth and volume, and finally depth and time to detect. RESULTS: We confirmed
      that the NIR light, 950-nm wavelength, used by the extravasation detection system
      is well absorbed by contrast media, making changes easy to detect. The average
      time to detect an extravasation was 2.05 seconds at a depth of 2.0 mm below the
      skin with a volume of 1.3 mL, 2.57 seconds at a depth between 2.1 and 5 mm below
      the skin and a volume of 3.47 mL, 10.5 seconds for depths greater than 5.1 mm and
      a volume of 11.1 mL. The detection accuracy was significantly deteriorated when
      the depth exceeded 5.0 mm (Tukey-Kramer, P < 0.05) CONCLUSIONS: The extravasation
      system detection system that is using NIR has a high level of detection
      sensitivity. The sensitivity enables the system to detect extravasation at depths
      less than 2 mm with a volume of 1.5 mL and at depths less than 5 mm with a volume
      of 3.5 mL. The extravasation detection system could be suitable for use during
      examinations.

PMID- 24448507
TI  - Achieving ideal computed tomographic scan length in patient with suspected
      urolithiasis.
AB  - PURPOSE: The purposes of the study were to determine the frequency and magnitude
      of extension of computed tomographic (CT) scans performed for the evaluation of
      urolithiasis, to investigate the potential contributing factors for overscanning,
      and to establish potential landmarks to assist in estimating the location of the
      superior margin of the kidneys. MATERIALS AND METHODS: This is a retrospective
      review of 300 CT studies performed for evaluation of urolithiasis. The total
      length of the scanned area, performing technologist, and the patient demographics
      were collected. RESULTS: We found that scanning beyond the defined z-axis
      boundaries is a common phenomenon in CT examinations in patients with suspected
      urolithiasis with a magnitude that correlates (P < 0.0001) with patient time and
      setting: greater in the emergent (78.3 mm) and inpatient (79.8 mm) settings as
      well as on-call hours (80.4 mm). Our study also shows the superior margin of T11
      to be consistently within 3 mm of the superior margin of the kidney but not below
      it. CONCLUSIONS: Overextension along the z axis is a ubiquitous phenomenon. The
      appropriate prescription of scan length, however, is an easy, efficient,
      costless, and universally applicable strategy. In patients with suspected
      urolithiasis, the superior margin of T11 represents a potential landmark to
      assist in estimating the upper margin of the kidneys.

PMID- 24448509
TI  - Reflections on success in multidisciplinary, translational science: working
      together to answer the right questions.

PMID- 24448510
TI  - The status of zinc in the development of hepatocellular cancer: an important, but
      neglected, clinically established relationship.
AB  - Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75%
      of HCC cases result in death generally within one year. The factors responsible
      for the initiation and progression of HCC remain largely unknown and speculative,
      thereby impeding advancements in the development of effective therapeutic agents
      and biomarkers for early detection of HCC. A consistent marked decrease in zinc
      in HCC tumors compared with normal liver is an established clinical relationship,
      which occurs in virtually all cases of HCC. However, this relationship has been
      largely ignored by the contemporary clinical and research community.
      Consequently, the factors and mechanisms involved in this relationship have not
      been addressed. Thus, the opportunity and potential for its employment as
      biomarkers for early identification of malignancy, and for development of a
      chemotherapeutic approach have been lacking. This presentation includes a review
      of the literature and the description of important recent and new data, which
      provide the basis for a concept of the role of zinc in the development of HCC.
      The basis is presented for characterizing HCC malignancy as ZIP14-deficient
      tumors, and its requirement to prevent zinc cytotoxic effects on the malignant
      cells. The potential for an efficacious zinc treatment approach for HCC is
      described. The involvement of zinc in the predisposition for HCC by chronic liver
      disease/cirrhosis is presented. Hopefully, this presentation will raise the
      awareness, interest, and support for the much needed research in the implications
      of zinc in the development and progression of HCC.

PMID- 24448511
TI  - A study on Nim expression in Bacteroides fragilis.
AB  - Members of the genus Bacteroides, mainly Bacteroides fragilis, can cause severe
      disease in man, especially after intestinal perforation in the course of
      abdominal surgery. Treatment is based on a small number of antibiotics, including
      metronidazole, which has proved to be highly reliable throughout the last 40 to
      50 years. Nevertheless, metronidazole resistance does occur in Bacteroides and
      has been mainly attributed to Nim proteins, a class of proteins with a suggested
      nitroreductase function. Despite the potentially high importance of Nim proteins
      for human health, information on the expression of nim genes in B. fragilis is
      still lacking. It was the aim of this study to demonstrate expression of nim
      genes in B. fragilis at the protein level and, furthermore, to correlate Nim
      levels with the magnitude of metronidazole resistance. By the application of 2D
      gel electrophoresis, Nim proteins could be readily identified in nim-positive
      strains, but their levels were not elevated to a relevant extent after induction
      of resistance with high doses of metronidazole. Thus, the data herein do not
      provide evidence for Nim proteins acting as nitroreductases using metronidazole
      as a substrate, because no correlation between Nim levels and levels of
      metronidazole resistance could be observed. Furthermore, no evidence was found
      that Nim proteins protect B. fragilis from metronidazole by sequestering the
      activated antibiotic. 

PMID- 24448513
TI  - Locally injected dexmedetomidine induces vasoconstriction via peripheral alpha-2A
      adrenoceptor subtype in guinea pigs.
AB  - BACKGROUND AND OBJECTIVES: Recent research shows that locally injected
      dexmedetomidine enhances the local anesthetic potency of lidocaine via the alpha
      2A adrenoceptor subtype in guinea pigs. However, little is known about the effect
      of locally injected dexmedetomidine on the peripheral vascular response. This
      study aimed to evaluate the effect of locally injected dexmedetomidine on the
      peripheral vascular response, measuring skin blood flow in the injected area in
      guinea pigs. METHODS: Dexmedetomidine was intracutaneously injected at a volume
      of 0.1 mL into the backs of guinea pigs, and further injected combined with
      yohimbine, a selective antagonist of alpha-2 adrenoceptors, or prazosin, a
      selective antagonist of alpha-1 adrenoceptors and an antagonist of both alpha-2B
      and alpha-2C adrenoceptor subtypes. Skin blood flow was measured until 60 minutes
      after injection using a laser-Doppler flowmeter. Furthermore, systemic arterial
      blood pressure and pulse of the guinea pigs were monitored via a catheter
      inserted into the carotid artery throughout every experiment. RESULTS:
      Dexmedetomidine at a concentration of 1 MUM significantly decreased the skin
      blood flow in a dose-dependent manner with no changes in the mean blood pressure
      and pulse. Yohimbine completely antagonized the effect of dexmedetomidine, but
      prazosin did not. CONCLUSIONS: The results reveal that locally injected
      dexmedetomidine at a concentration of 1 MUM induced peripheral vasoconstriction
      without a systemic cardiovascular response via the peripheral alpha-2A
      adrenoceptor subtype.

PMID- 24448512
TI  - Treatment of postmastectomy pain with ambulatory continuous paravertebral nerve
      blocks: a randomized, triple-masked, placebo-controlled study.
AB  - BACKGROUND: We aimed to determine with this randomized, triple-masked, placebo
      controlled study if benefits are afforded by adding a multiple-day, ambulatory,
      continuous ropivacaine paravertebral nerve block to a single-injection
      ropivacaine paravertebral block after mastectomy. METHODS: Preoperatively, 60
      subjects undergoing unilateral (n = 24) or bilateral (n = 36) mastectomy received
      either unilateral or bilateral paravertebral perineural catheter(s),
      respectively, inserted between the third and fourth thoracic transverse
      process(es). All subjects received an initial bolus of ropivacaine 0.5% (15 mL)
      via the catheter(s). Subjects were randomized to receive either perineural
      ropivacaine 0.4% or normal saline using portable infusion pump(s) [5 mL/h basal;
      300 mL reservoir(s)]. Subjects remained hospitalized for at least 1 night and
      were subsequently discharged home where the catheter(s) were removed on
      postoperative day (POD) 3. Subjects were contacted by telephone on PODs 1, 4, 8,
      and 28. The primary end point was average pain (scale, 0-10) queried on POD 1.
      RESULTS: Average pain queried on POD 1 for subjects receiving perineural
      ropivacaine (n = 30) was a median (interquartile) of 2 (0-3), compared with 4 (1
      5) for subjects receiving saline (n = 30; 95% confidence interval difference in
      medians, -4.0 to -0.3; P = 0.021]. During this same period, subjects receiving
      ropivacaine experienced a lower severity of breakthrough pain (5 [3-6] vs 7 [5
      8]; P = 0.046) as well. As a result, subjects receiving perineural ropivacaine
      experienced less pain-induced physical and emotional dysfunction, as measured
      with the Brief Pain Inventory (lower score = less dysfunction): 14 (4-37) versus
      57 (8-67) for subjects receiving perineural saline (P = 0.012). For the subscale
      that measures the degree of interference of pain on 7 domains, such as general
      activity and relationships, subjects receiving perineural saline reported a
      median score 10 times higher (more dysfunction) than those receiving ropivacaine
      (3 [0-24] vs 33 [0-44]; P = 0.035). In contrast, after infusion discontinuation,
      there were no statistically significant differences detected between treatment
      groups. CONCLUSIONS: After mastectomy, adding a multiple-day, ambulatory,
      continuous ropivacaine infusion to a single-injection ropivacaine paravertebral
      nerve block results in improved analgesia and less functional deficit during the
      infusion. However, no benefits were identified after infusion discontinuation.

PMID- 24448514
TI  - Selective electrocatalysts toward a prototype of the membraneless direct methanol
      fuel cell.
AB  - Mastery over the structure of nanomaterials enables control of their properties
      to enhance their performance for a given application. Herein we demonstrate the
      design and fabrication of Pt-based nanomaterials with enhanced catalytic activity
      and superior selectivity toward the reactions in direct methanol fuel cells
      (DMFCs) upon the deep understanding of the mechanisms of these electrochemical
      reactions. In particular, the ternary Au@Ag2S-Pt nanocomposites display superior
      methanol oxidation reaction (MOR) selectivity due to the electronic coupling
      effect among different domains of the nanocomposites, while the cage-bell
      structured Pt-Ru nanoparticles exhibit excellent methanol tolerance for oxygen
      reduction reaction (ORR) at the cathode because of the differential diffusion of
      methanol and oxygen in the porous Ru shell of the cage-bell nanoparticles. The
      good catalytic selectivity of these Pt-based nanomaterials via structural
      construction enables a DMFC to be built without a proton exchange membrane
      between the fuel electrode and the oxygen electrode. 

PMID- 24448515
TI  - Preparation of molecular imprinted microspheres based on inorganic-organic co
      functional monomer for miniaturized solid-phase extraction of fluoroquinolones in
      milk.
AB  - An inorganic-organic co-functional monomer, methacrylic acid-vinyltriethoxysilan
      (MAA-VTES) was designed for the synthesis of molecularly imprinted microspheres
      (MIMs). By virtue of the aqueous suspension polymerization and dummy template
      (pazufloxacin), the obtained MAA-VTES based MIMs exhibited good recognition and
      selectivity to fluoroquinolones (FQs), and were successfully applied as selective
      sorbents of a miniaturized home-made solid phase extraction device for the
      determination of ofloxacin (OFL), lomefloxacin (LOM) and ciprofloxacin (CIP) in
      milk samples. Under the optimum conditions of the miniaturized molecularly
      imprinted solid phase extraction (mini-MISPE) coupled with liquid chromatography
      ultraviolet detector (LC-UV), good linearities were obtained for three FQs in a
      range of 0.2-20.0MUgmL(-1) and the average recoveries at three spiked levels were
      ranged from 87.2% to 106.1% with the relative standard deviation (RSD) less than
      5.4%. The presented co-functional monomer based mini-MISPE-LC-UV protocol
      introduced the rigidity and flexibility of inorganic silicon materials, exhibited
      excellent extraction performance towards targets, and could be potentially
      applied to the determination of FQs in milk samples. 

PMID- 24448517
TI  - What's so special about verbal imitation? Investigating the effect of modality on
      automaticity in children.
AB  - Young children experience difficulty across a wide variety of situations that
      require them to suppress automatic responses. Verbal imitation, in contrast, is
      easy for children to suppress. This is all the more surprising because data from
      adult studies appear to be at odds with this observation. In two experiments, we
      investigated whether this surprising developmental finding with verbal imitation
      reflects a more general phenomenon-relating either to verbal responses or to
      auditory stimuli-or whether verbal imitation itself represents a unique case. In
      Experiment 1 (N=24), it was found that verbal responses were not inherently
      easier for 3-year-olds to inhibit than manual responses. Experiment 2 (N=24)
      showed that auditory stimuli did not evoke less automatic activation than visual
      stimuli. Taken together, these data suggest that verbal imitation is unique, or
      at least unusual, in being particularly easy for children to resist. It is
      suggested that the automaticity of verbal imitation may develop slowly and that
      the relation between word complexity and automaticity is likely to be a fruitful
      topic of further investigation. 

PMID- 24448516
TI  - Intra-articular injection of human meniscus stem/progenitor cells promotes
      meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived
      factor-1/CXCR4-mediated homing.
AB  - Meniscus injury is frequently encountered in clinical practice. Current surgical
      therapy involving partial or complete meniscectomy relieves pain in the short
      term but often leads to osteoarthritis (OA) in the long-term. In this study, we
      report a new strategy of articular cartilage protection by intra-articular
      injection of novel human meniscus stem/progenitor cells (hMeSPCs). We found that
      hMeSPCs displayed both mesenchymal stem cell characteristics and high expression
      levels of collagen II. In the rat meniscus injury model, hMeSPC transplantation
      not only led to more neo-tissue formation and better-defined shape but also
      resulted in more rounded cells and matured extracellular matrix. Stromal cell
      derived factor-1 (SDF-1) enhanced the migration of hMeSPCs, whereas AMD3100
      abolished the chemotactic effects of SDF-1 on hMeSPCs, both in vitro and in vivo.
      In an experimental OA model, transplantation of hMeSPCs effectively protected
      articular cartilage, as evidenced by reduced expression of OA markers such as
      collagen I, collagen X, and hypoxia-inducible factor 2alpha but increased
      expression of collagen II. Our study demonstrated for the first time that intra
      articular injection of hMeSPCs enhanced meniscus regeneration through the SDF
      1/CXCR4 axis. Our study highlights a new strategy of intra-articular injection of
      hMeSPCs for meniscus regeneration. 

PMID- 24448518
TI  - Reading scripts that differ in orthographic transparency: a within-participant
      and-language investigation of underlying skills.
AB  - Spelling-sound transparency varies across orthographies. This aspect was found to
      have implications for the strategy of reading, but whether reading of different
      orthographies also relies differently on cognitive skills is yet unclear. This
      question was examined mainly by cross-participant-and-language investigations in
      which orthographic variation is hard to isolate. This work examined this topic
      using a within-participant-and-language study design. Hebrew readers in Grades 3
      and 4 were longitudinally tested because in these grades they are engaged in
      reading three forms of script, transcribing the same language and varying in
      spelling-sound relations, as they gradually progress from reading a transparent
      orthography to reading an opaque one. Phonological awareness explained a
      considerable amount of variance in accuracy in reading all forms of script across
      these two years. The relations of morphological awareness with accuracy in
      reading the three forms of script were similar; however, the results suggested
      that these may be associated with the course of transition. Phonological
      awareness and rapid naming were similarly related to fluency in reading all forms
      of script when equivalent proficiencies in reading of these scripts were
      achieved. At this stage, the relations of vocabulary with fluency in reading and
      comprehension of the transparent and opaque forms of script were also much alike.
      Phonological memory explained a modest, but significant, amount of variance in
      comprehension of the unpointed script alone. These results suggest that, apart
      from phonological memory, the cognitive skills tested in this study serve as a
      common cognitive infrastructure in reading orthographies varying in spelling
      sound transparency. 

PMID- 24448519
TI  - The production of spontaneous false memories across childhood.
AB  - We found evidence that the usual developmental trends in children's spontaneous
      false memories were eliminated using novel stimuli containing obvious themes.
      That is, children created more false memories than adults when scenes needed to
      be remembered. In Experiment 1, 7- and 8-year-olds had higher false memory rates
      than adults when using visual scenes. Experiment 2 showed that gist cuing could
      not account for this effect. In Experiment 3, children and adults received visual
      scenes and story contexts in which these scenes were embedded. For both types of
      stimuli, we found that children had the highest false memory rates. Our results
      indicate that the underlying theme of these scenes is easily identified,
      resulting in our developmental false memory trend. 

PMID- 24448520
TI  - The impact of distracter-target similarity on contextual cueing effects of
      children and adults.
AB  - Contextual cueing reflects a memory-based attentional guidance process that
      develops through repeated exposure to displays in which a target location has
      been consistently paired with a specific context. In two experiments, we compared
      20 younger children's (6-7 years old), 20 older children's (9-10 years old), and
      20 young adults' (18-21 years old) abilities to acquire contextual cueing effects
      from displays in which half of the distracters predicted the location of the
      target and half did not. Across experiments, we varied the similarity between the
      predictive and nonpredictive distracters and the target. In Experiment 1, the
      predictive distracters were visually similar to the target and dissimilar from
      the nonpredictive distracters. In Experiment 2, the nonpredictive distracters
      were also similar to the target and predictive distracters. All three age groups
      exhibited contextual cueing in Experiment 1, although the effect was not as
      strong for the younger children relative to older children and adults. All
      participants exhibited weaker contextual cueing effects in Experiment 2, with the
      younger children not exhibiting significant contextual cueing at all. Apparently,
      when search processes could not be guided to the predictive distracters on the
      basis of salient stimulus features, younger children in particular experienced
      difficulty in implicitly identifying and using aspects of the context to
      facilitate with the acquisition of contextual cueing effects.

PMID- 24448521
TI  - Extracranial orbital meningioma extending into the nasosinus in neurofibromatosis
      type 2.
AB  - PURPOSE: The purpose of this study was to report a rare case of neurofibromatosis
      type 2 (NF2) with extracranial orbital meningioma extending into the frontal and
      ethmoidal sinuses. METHODS: This is clinical report of a 17-year-old male patient
      with NF2. Results of an ocular examination, computed tomography scan, and
      pathological findings of space-occupied orbital and nasosinus lesions are
      presented. RESULTS: Computed tomography scan revealed a high-density soft tissue
      mass occupying the right superionasal orbit extending into the frontal and
      ethmoidal sinuses and bilateral acoustic schwannomas in the brain. Biopsy of the
      right orbital lesion demonstrated a typical meningioma as indicated with routine
      hematoxylin-eosin staining and immunohistochemical evaluation. CONCLUSIONS: In
      this patient, an extracranial orbital meningioma, rather than optic nerve sheath
      meningioma extending into nasosinus, designates a diagnosis of NF2.
      Ophthalmologists should be aware of the possibility that patients with an
      extracranial orbital meningioma may also have NF2.

PMID- 24448523
TI  - Combined metopic and unilateral coronal synostoses: a phenotypic conundrum.
AB  - BACKGROUND: Most types of craniosynostosis cause predictable changes in cranial
      shape. However, the phenotype of combined metopic and unilateral coronal
      synostoses is anomalous. The purpose of this observational study was to better
      clarify the clinical and radiographic features of this rare entity. METHODS: A
      retrospective review of a craniofacial database was performed. Patients with
      combined metopic and unilateral coronal synostoses were included in this study.
      Data collected included demographic information, physical and radiographic
      findings, genetic evaluation, treatment, and operative outcomes. RESULTS: Of 687
      patients treated between 1989 and 2010, only 3 patients had combined metopic and
      unilateral coronal synostoses. All patients were diagnosed through computed
      tomography on the first day of life. Phenotypic features included the following:
      (1) narrowed forehead with a prominent midline ridge, (2) severe bilateral brow
      retrusion with an acute indentation on the side of the patient coronal suture,
      (3) facial and nasal angulation similar to isolated unilateral coronal
      synostosis, and (4) anterior displacement of the ear on the fused side. In
      addition, the cranial vertex was deviated toward the side of the open coronal
      suture. Two patients had a head circumference below the 25th percentile; 2 of the
      3 had a TWIST gene mutation consistent with Saethre-Chotzen syndrome. One patient
      was managed through fronto-orbital advancement and required a revision. The other
      2 patients had early endoscopic release, followed by postoperative helmet
      therapy; one improved but still required open cranial remodeling. The other has
      near-normal phenotype, and no further surgery is planned. CONCLUSIONS: Combined
      metopic and unilateral coronal synostoses present a rare and unusual phenotype.
      Although early intervention improves the deformity, revisional procedures are
      usually required.

PMID- 24448524
TI  - The dragonfly splint: a new disposable device designed to prevent both medial and
      lateral turbinate synechiae after sinonasal surgery.
AB  - Periturbinal adhesions are among the most frequent and challenging complications
      of sinonasal surgery. Endonasal paraseptal splints have proved to be very
      efficient in preventing "medial synechiae," that is, adhesions located between
      the medial faces of the middle/inferior turbinates and the septum. However, none
      of these devices for guiding mucosal healing can prevent "lateral synechiae"
      (adhesions between the lateral face of the middle turbinate and the lateral nasal
      wall) inside the middle meatal cleft, which is a very critical area for the
      physiology of the anterior sinus system. For this reason, if followed by the
      formation of lateral synechiae, the surgical maneuvers used to treat sinus
      diseases could paradoxically become a cause of persistent functional impairment
      and lead to iatrogenic sinusitis or mucocele.We describe our preliminary
      experience with a new endonasal splint called "Dragonfly" (because of its shape),
      which has been designed to prevent both medial and lateral postsurgical
      synechiae. This device has a long lateral wing designed to separate the mucosal
      surfaces of the middle meatal/ethmoid cavities and prevent adhesions during the
      postoperative process of healing. The device must be kept in situ for 3 to 4
      weeks to permit the re-epithelialization of the internal nasal surfaces. Our
      experience shows that the splints are well tolerated and highly efficient,
      preventing both medial and lateral synechiae in 100% of cases. A randomized
      controlled study has now been started to confirm these positive preliminary
      findings in a larger patient population. 

PMID- 24448522
TI  - Hemimandibular hyperplasia: classification and treatment algorithm revisited.
AB  - Hemimandibular hyperplasia (HH) is a developmental asymmetry characterized by
      three-dimensional enlargement of one half of the mandible. The hyperplastic side
      usually involves the condyle, condylar neck, ramus, and body, with the anomaly
      terminating abruptly at the symphysis. The malformation results in the clinical
      presentation of ipsilateral enlargement of the mandible and tilted occlusal
      plane, associated with a deviated chin to the contralateral side. Since the first
      case report of HH in the English literature in 1836, various terminology and
      classifications were used. In this study, the authors classified the patients
      into typical and atypical types of HH on the basis of clinical and radiologic
      observations in an effort to achieve a simplified and efficient surgical
      management on the basis of the severity of deformity. Accordingly, surgical
      treatments are designed respectively on the basis of the authors' classification
      and treatment algorithm. In addition, in view of potential complications arising
      from condylectomy, none of the patients had undergone condylectomy as part of the
      surgical treatment. The authors present their experience on the basis of this
      proposed classification and treatment algorithm with functional and aesthetic
      outcomes as the end points of this study. 

PMID- 24448525
TI  - Squamosal suture craniosynostosis in Muenke syndrome.
AB  - Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in
      30,000 newborns and accounts for 25% to 30% of genetic causes of
      craniosynostosis. Anomalies in patients with Muenke syndrome include
      craniosynostosis, hypertelorism, sensorineural hearing loss, and developmental
      delay, among others. Most craniosynostoses in patients with Muenke syndrome
      involve bicoronal suture fusion. This article reports, for the first time, the
      existence of squamosal craniosynostosis in patients with Muenke syndrome. 

PMID- 24448526
TI  - Sarcomatous transformation of osteochondroma of the coronoid process forming
      pseudoarthrosis with zygomatic arch mistaken for Jacob disease.
AB  - Osteochondromas are the most common benign osseous neoplasms, with a propensity
      to involve long bones. The involvement of the coronoid process is extremely rare,
      and osteochondromas of the coronoid process may form pseudoarticulations with the
      zygomatic arch when large, an entity that is extremely rare and termed as Jacob
      disease. Sarcomatous degeneration of osteochondroma of the coronoid process is an
      extremely rare entity and has not been described to date. Only 1 case of primary
      mesenchymal chondrosarcoma has been described. We present a case of a 24-year-old
      man with a chondrosarcoma of the coronoid process, who was wrongly diagnosed with
      Jacob disease on the basis of radiologic findings. 

PMID- 24448527
TI  - Perioperative difficulties and early postoperative complications of transoral
      approach in mouth base surgery.
AB  - OBJECTIVE: The aim of this study was to discuss perioperative difficulties and
      temporary or permanent complications that can be seen at early postoperative
      period in cases undergoing transoral surgical approach for disorders of mouth
      base. STUDY DESIGN: The study included 19 patients undergoing transoral surgical
      approach between September 2011 and January 2013 who were retrospectively
      evaluated. Exclusion criteria were patients with malign submandibular gland tumor
      or other suspected tumors at mouth base, those with a benign solid mass larger
      than 10 * 10 cm, and those who did not accept the transoral approach. RESULTS:
      Mean age was 28.47 +/- 17.89 years (range, 8-76 years) in 19 patients included (9
      male and 10 female subjects). Of these, submandibular gland excision was
      performed in 9 cases, whereas thyroglossal duct cyst excision was performed in 3
      (2 transfrenulum approach and 1 lateral lingual approach), lymphangioma excision
      in 1, diagnostic lymph node excision at the posterior of submandibular gland in 3
      cases, and dermoid cyst excision (2 with midline and 1 with left submandibular
      localization) in 3 cases. Perioperative difficulties included dissection problems
      due to adhesion, partial adhesion between Wharton canal and lingual nerve,
      fragmented dissection of the gland, capsule rupture of submandibular adenoma, and
      facial artery rupture. While visualization of surgical field and retraction of
      mouth base muscles are an important issue in midline approaches, resection of
      hyoid bone corpus is challenging in lateral approaches. Early postoperative
      complications included edema at mouth base, lingual ecchymosis, and postoperative
      temporary abnormal tongue sensation. CONCLUSIONS: Transoral mouth base surgery is
      a safe approach in selected patients. Permanent injuries of neural structures are
      rarely encountered, which is considered as a concern by head and neck surgeons.
      Temporary complications are at a level that can be tolerated by patients.

PMID- 24448528
TI  - Endoscopic endonasal marsupialization of nasopalatine duct cyst.
AB  - Nasopalatine duct cyst is one of the most common cysts among the nonodontogenic
      cysts in the maxillofacial area. This lesion usually does not show specific
      symptoms except for pressure from large cysts or infectious symptoms. Surgical
      removal including the epithelial lining is considered the treatment of choice.
      There are few reports of cases of endoscopic marsupialization treatment of large
      cysts, which have the risk of oronasal fistula. Here, we reviewed 3 cases of
      nasopalatine duct cyst treated with intranasal marsupialization and compared
      treatment results with those of conventional surgical enucleation. We suggest
      that endoscopic marsupialization could be used as an initial treatment option in
      selective cases. 

PMID- 24448529
TI  - Morphological study of surgical approach by superior temporal sulcus-temporal
      horn of lateral ventricle approach using volume rendering.
AB  - In this research, we acquired the length of the superior temporal sulcus, the
      shortest distance from the superior temporal sulcus to the temporal horn of the
      lateral ventricle, and the approach angle between the median sagittal plane and
      the shortest segment from the superior temporal sulcus to the temporal horn of
      the lateral ventricle measuring 98 specimens by magnetic resonance imaging volume
      rendering. At the same time, we preliminarily oriented the point of the superior
      temporal sulcus, which is closest to the temporal horn of the lateral ventricle,
      aimed at finding out the best entrance point of surgical approach through the
      superior temporal sulcus to the temporal horn of the lateral ventricle and
      reducing the damage to optic radiation as well as other nerve fibers during the
      operation. The results indicate that the point at the front side 3/5 of the
      superior temporal sulcus may be the ideal surgical approach entrance point, and
      there is no difference between 2 cerebral hemispheres (P < 0.05). 

PMID- 24448530
TI  - An anatomic study of the medial fibers of depressor anguli oris muscle passing
      deep to the depressor labii inferioris muscle.
AB  - The trajectory of the medial fibers of depressor anguli oris muscle that pass
      deep to the depressor labii inferioris muscle (dDAO) and the anatomic
      relationship have not yet been examined. The aim of this study was to clarify the
      arrangement of the dDAO and its relationships with the surrounding structures.
      The dDAOs were investigated in 40 hemifaces from Korean cadavers. The dDAOs were
      observed in 18 of the 40 specimens (45%). The anatomic relationships of the dDAO
      were classified into the following 4 categories according to their connection
      with the incisivus labii inferioris muscle (ILI): (1) connected to the ILI and
      attached to the inferior border of the mandible lateral to the mentalis muscle
      (14 specimens, 35%), (2) connected to the ILI and intermingled with the lateral
      lower fibers of the mentalis muscle (2 specimens, 5%), (3) connected to the ILI
      but neither attached to the mandible nor intermingled with the mentalis muscle (1
      specimen, 2.5%), and (4) not connected to the ILI but intermingled with the
      mentalis muscle (1 specimen, 2.5%). Therefore, in 17 specimens, the dDAOs were
      connected to the ILI (42.5%), in 14 specimens, they were attached to the inferior
      border of the mandible (35%), and, in 3 specimens, they were intermingled with
      the mentalis muscle (7.5%). The new anatomic data regarding the dDAO will
      contribute toward the understanding of movements of the mouth and lower face,
      which will be helpful when designing effective botulinum toxin type A therapies
      and performing various types of facial surgery. 

PMID- 24448531
TI  - Types of endoscopic endonasal resections for sinonasal malignancies.
AB  - AIM: The aim of this study was to define the types of endoscopic endonasal
      resection for sinonasal malignancies according to their origin and extension.
      METHODS: Patients who underwent endoscopic endonasal surgery for the removal of
      malignant tumors of the nasal passages, paranasal sinuses, and the anterior
      cranial base between 2003 and 2010 were included in the study. Patients' data
      were collected retrospectively. Patients were grouped according to types of
      endoscopic tumor resection as follows: type I: en bloc resection, type II:
      resection of intranasal free part piecemeal and origin of tumor en bloc, type
      III: resection of intranasal free part and origin of tumor piecemeal with
      curative intent, and type IV: resection of intranasal free part and origin of
      tumor piecemeal with palliative intent or removal of tumor with positive margin.
      The follow-up period varied from 2 to 7 years (mean, 4.35 years). RESULTS: Twenty
      patients were included in the study. Five patients underwent type I, 6 patients
      type II, 4 patients type III, and 5 patients underwent type IV resection. No
      local tumor recurrence was seen after types I, II, and III resections, whereas 2
      patients (10%) with the type IV resection had a local recurrence. Distant
      metastasis was observed in 4 patients (20%) postoperatively (1 patient in type I,
      1 patient in type III, and 2 patients in type IV resection). Disease-specific
      death was 15% (1 case in type I and 2 cases in type IV). CONCLUSION:
      Classification of endoscopic tumor resection used in the present study may help
      preoperative planning.

PMID- 24448532
TI  - Maxillary sinus floor elevation via crestal approach: the evolution of the
      hydraulic pressure technique.
AB  - The current study describes an innovative protocol for the surgical maxillary
      sinus augmentation via a crestal approach that uses hydraulic pressure to lift
      the Schneiderian membrane and simultaneously fill the subantral space with a
      biomaterial for bone regeneration (nanocrystalline hydroxyapatite in aqueous
      solution). The technique in question combines the advantages of large amounts of
      grafted biomaterial with reduced trauma, high precision, and predictability. 

PMID- 24448533
TI  - Repair of a pediatric bilateral condylar and symphyseal fracture using a
      transfacial Steinman pin.
AB  - The proper management of complex pediatric mandibular fractures remains a topic
      of debate because of the relatively uncommon presentation of these fractures,
      combined with concerns related with deciduous teeth, tooth buds, and growth
      inhibition. In this current study, we present a novel approach to the repair of
      bilateral condylar fractures with concomitant symphyseal fracture in a 4-year-old
      girl. Manual closed reduction was first obtained, followed by placement of a
      transfacial Steinman pin through the angles of the mandible and placement of
      circummandibular wires. Maxillomandibular fixation remained for 2 weeks and the
      Steinman pin was removed after 11 weeks. At 3 months of postsurgical follow-up,
      the patient displayed class I occlusion, facial symmetry, full range of jaw
      motion, and absence of deviation or pain on full oral excursion. Radiographic
      findings also revealed complete resolution of the symphyseal fracture with
      appropriate condylar healing and alignment. 

PMID- 24448534
TI  - The experience of neurofibromatosis type I originating from pterygopalatine fossa
      and salivary gland.
AB  - One patient of neurofibromatosis type I originating from the pterygopalatine
      fossa and salivary gland underwent surgery in our department. At the outset, the
      case was misdiagnosed as arising from salivary gland tumors, and surgery was
      immediately performed. The tumor was entered directly, which induced ferocious
      bleeding. The subsequent hemostasis with tamponade and compression caused
      intracranial venous sinus thrombosis, which induced irreversible intracranial
      complications and finally resulted in death. The experience regarding the
      diagnosis and treatment of the case was retrospectively reviewed and shared in
      this article. 

PMID- 24448535
TI  - Determining the morphometry and variations of the confluens sinuum and related
      structures via a silicone painting technique on autopsy patients.
AB  - In this study, we aimed to investigate the morphometric and morphologic
      structures of the confluens sinuum (CS) and related structures with a silicone
      painting technique. We studied 30 cadavers. Twelve of them were washed with
      alcohol and filled with a silicone painting technique via the vena jugularis
      interna, internal carotid artery, and vertebral artery. The other 18 were
      autopsied postmortem. The CS and related structures were dissected under
      microscope. Their anatomy was investigated, and variations were noted. The
      diameters of the sinus sagittalis superior (SSS), CS, occipital sinus (OS), sinus
      rectus (SR), and bilateral transverse sinus (TS), and the angle between SSS and
      SR were measured. The mean diameters were 11.7 mm for SSS, 22.3 mm for CS, 5.25
      mm for OS, 7.5 mm for SR, and 9.7 (right) and 9.1 mm (left) for TS. The angle
      between the SR and SSS was 58 degrees . There was no difference in the bilateral
      venous structures that drained to the SSS and TS. There was an extra drainage to
      the CS from the left side in 4 cases. The right TS was located superiorly in 7
      cases compared with the left TS, and this process was correlated with the type of
      CS. A septum in the SSS was detected in 2 cases. In addition, we encountered an
      OS in 80% of the cases. We conclude that the septum inside the CS affects the
      dominancy of the TS, the angle between the SSS and SR, and the other venous
      variations. 

PMID- 24448537
TI  - Block bone graft fixation (onlay): a modification of the surgical technique.
AB  - Several reconstructive methods of the alveolar ridge have been reported to make
      possible future rehabilitations with implants. Many of these methods come from
      studies done in animals, mainly rats. With this clinical practice based on
      scientific evidence, any experimental procedure that can be undertaken in real
      life is fundamental. Thus, any research that emulates as closely as possible
      those techniques used in humans are important. This study describes the
      modification of the technique for block bone graft fixation (onlay) in rats using
      the "lag screw"-type technique, normally used in clinical procedures for grafts
      in humans. The conclusion was that the execution of the described procedures
      minimizes interference of blood flow in the area because of the maintenance of
      the muscle insertion in the buckle aspect of the most anterior region of the
      mandible, providing better stability to the graft and better contact interface of
      the graft and receptor bed. 

PMID- 24448536
TI  - Technical strategies for en bloc resection and immediate reconstruction in
      hemangioma of the frontal bone.
AB  - Hemangioma of the skull is a benign solitary tumor, often found in the frontal or
      parietal area. A hemangioma lesion typically involves the outer table rather than
      the inner, but its complete removal at the diploe level is difficult. Full
      thickness resection at the calvaria is often needed to ensure a free margin, but
      it will leave a bony defect that requires reconstruction. Although curettage and
      covering of the lesion with alloplastic material are a simple treatment option
      for hemangioma of the skull, it does not always prevent recurrence. Hence,
      complete resection is needed. As our technical strategies for reconstruction, we
      organize a split calvarial bone graft if a defect is near the frontal sinus and
      calcium phosphate cement if it is somewhat far from the sinus. 

PMID- 24448538
TI  - Evaluation of three-dimensional position change of the condylar head after
      orthognathic surgery using computer-aided design/computer-aided manufacturing
      made condyle positioning jig.
AB  - This study was performed to evaluate the efficacy of computer-aided
      design/computer-aided manufacturing (CAM/CAD)-made condyle positioning jig in
      orthognathic surgery. The sample consisted of 40 mandibular condyles of 20
      patients with class III malocclusion who underwent bilateral sagittal split ramus
      osteotomy with semirigid fixation (6 men and 14 women; mean age, 25 y; mean
      amount of mandibular setback, 5.8 mm). Exclusion criteria were patients who
      needed surgical correction of the frontal ramal inclination and had signs and
      symptoms of the temporomandibular disorder before surgery. Three-dimensional
      computed tomograms were taken 1 month before the surgery (T1) and 1 day after the
      surgery (T2). The condylar position was evaluated at the T1 and T2 stages on the
      axial, frontal, and sagittal aspects in the three-dimensional coordinates. The
      linear change of the posterior border of the proximal segment of the ramus
      between T1 and T2 was also evaluated in 30 condyles (15 patients), with the
      exception of 10 condyles of 5 patients who received mandibular angle reduction
      surgery. There was no significant difference in the condylar position in the
      frontal and sagittal aspects (P > 0.05). Although there was a significant
      difference in the condylar position in the axial aspect (P < 0.01), the amount of
      difference was less than 1 mm and 1 degree; it can be considered clinically
      nonsignificant. In the linear change of the posterior border of the proximal
      segment of the ramus, the mean change was 1.4 mm and 60% of the samples showed a
      minimal change of less than 1 mm. The results of this study suggest that CAD/CAM
      made condyle positioning jig is easy to install and reliable to use in
      orthognathic surgery. 

PMID- 24448539
TI  - Great auricular nerve preservation during parotidectomy for benign tumors.
AB  - The great auricular nerve, the largest sensory branch of the cervical plexus,
      arises from the third cervical nerve (C3) with irregular contribution from the
      C2. The first part of its course is deep to the sternocleidomastoid muscle. In
      few years, many experiences by different authors concerning the issue of great
      auricular nerve integrity during parotidectomy were published in the literature.
      The aims of our article were to report our experience with 78 consecutive
      patients who underwent standard superficial, subtotal, or total parotidectomy for
      benign tumors and to illustrate postsurgical findings regarding the sensibility
      of the pinna and mandibular angle as subjectively reported in the early
      postsurgical period and after 3, 6, and 12 months from surgery. 

PMID- 24448540
TI  - Prosthodontic rehabilitation after myofascial flap surgery of hemimaxillectomy
      defects in the edentulous patient: a clinical report.
AB  - OBJECTIVE: The aims of this clinical report were to present and discuss the
      clinical procedure and the treatment considerations of prosthetic rehabilitation
      after myofascial flap surgery. DESIGN: A 78-year-old edentulous woman with a
      squamous cell carcinoma underwent hemimaxillectomy. A temporalis myofascial flap
      surgery combined with implant-supported prosthesis is one successful approach to
      the restoration of oral function after hemimaxillectomy. CONCLUSIONS: Although
      the bulky and mobile nature of a temporalis myofascial flap prevented the
      retention of a tissue-borne denture, an appropriate impression technique and the
      fabrication of implant-supported prosthesis using an implant attachment system
      enhanced the overall satisfaction by the patient.

PMID- 24448541
TI  - Three-dimensional anatomic analysis of the lingula and mandibular foramen: a cone
      beam computed tomography study.
AB  - PURPOSE: The authors analyzed the anatomic location differences of the mandibular
      foramen (MF) and lingula in a cone beam computed tomography study, aiming to
      obtain information that could be used when performing mandibular osteotomies and
      the inferior alveolar nerve block (IANB). METHODS: Three-dimensional mandibular
      computed tomography images were reconstructed from data for 139 patients (278
      sides) aged between 9 and 18 years (growth group, 27 patients) and aged 19 to 71
      years (adult group, 112 patients). RESULTS: In the adult group, positive
      correlations were seen between right and left measurements. In the growth group,
      there are significant differences in lingula-anterior and MF-posterior ramus
      measurements. In the adult group, there are significant differences between man
      and woman MF-gonion distance measurements. Differences were seen in edentulous
      and asymmetry patients. CONCLUSIONS: The MF is an important anatomic landmark for
      ramus surgery and IANB. When applied to ramus operations and IANB, the anatomic
      data provided by this study may help surgeons gain more understanding of nerve
      position during surgery.

PMID- 24448542
TI  - An alternative method for facial resurfacing: supraclavicular skin prefabrication
      by perforator fascia flap.
AB  - Prefabrication of supraclavicular skin provides a useful source for flaps
      congruent with the face skin. Among various vascular sources that have been used
      for this purpose, anterolateral thigh fascia seems to represent a greater value
      because of having a long and strong vascular pedicle and negligible donor-site
      morbidity. In this regard, we present a technical report on using the lateral
      circumflex femoral artery perforator flap harvest technique in preparing an
      anterolateral thigh fascia flap for the prefabrication of the supraclavicular
      skin. The technique proved successful in resurfacing the facial skin of a young
      female patient with a giant congenital melanocytic hairy nevus on the left side
      of her face. 

PMID- 24448543
TI  - DNA polymorphism and epigenetic marks modulate the affinity of a scaffold/matrix
      attachment region to the nuclear matrix.
AB  - Mechanisms that regulate attachment of the scaffold/matrix attachment regions
      (S/MARs) to the nuclear matrix remain largely unknown. We have studied the effect
      of simple sequence length polymorphism (SSLP), DNA methylation and chromatin
      organization in an S/MAR implicated in facioscapulohumeral dystrophy (FSHD), a
      hereditary disease linked to a partial deletion of the D4Z4 repeat array on
      chromosome 4q. This FSHD-related nuclear matrix attachment region (FR-MAR) loses
      its efficiency in myoblasts from FSHD patients. Three criteria were found to be
      important for high-affinity interaction between the FR-MAR and the nuclear
      matrix: the presence of a specific SSLP haplotype in chromosomal DNA, the
      methylation of one specific CpG within the FR-MAR and the absence of histone H3
      acetylated on lysine 9 in the relevant chromatin fragment. 

PMID- 24448544
TI  - The 'extremely ancient' chromosome that isn't: a forensic bioinformatic
      investigation of Albert Perry's X-degenerate portion of the Y chromosome.
AB  - Mendez and colleagues reported the identification of a Y chromosome haplotype
      (the A00 lineage) that lies at the basal position of the Y chromosome
      phylogenetic tree. Incorporating this haplotype, the authors estimated the time
      to the most recent common ancestor (TMRCA) for the Y tree to be 338,000 years ago
      (95% CI=237,000-581,000). Such an extraordinarily early estimate contradicts all
      previous estimates in the literature and is over a 100,000 years older than the
      earliest fossils of anatomically modern humans. This estimate raises two
      astonishing possibilities, either the novel Y chromosome was inherited after
      ancestral humans interbred with another species, or anatomically modern Homo
      sapiens emerged earlier than previously estimated and quickly became subdivided
      into genetically differentiated subpopulations. We demonstrate that the TMRCA
      estimate was reached through inadequate statistical and analytical methods, each
      of which contributed to its inflation. We show that the authors ignored
      previously inferred Y-specific rates of substitution, incorrectly derived the Y
      specific substitution rate from autosomal mutation rates, and compared unequal
      lengths of the novel Y chromosome with the previously recognized basal lineage.
      Our analysis indicates that the A00 lineage was derived from all the other
      lineages 208,300 (95% CI=163,900-260,200) years ago.

PMID- 24448546
TI  - Trends in genetic patent applications: the commercialization of academic
      intellectual property.
AB  - We studied trends in genetic patent applications in order to identify the trends
      in the commercialization of research findings in genetics. To define genetic
      patent applications, the European version (ECLA) of the International Patent
      Classification (IPC) codes was used. Genetic patent applications data from the
      PATSTAT database from 1990 until 2009 were analyzed for time trends and regional
      distribution. Overall, the number of patent applications has been growing. In
      2009, 152 000 patent applications were submitted under the Patent Cooperation
      Treaty (PCT) and within the EP (European Patent) system of the European Patent
      Office (EPO). The number of genetic patent applications increased until a peak
      was reached in the year 2000, with >8000 applications, after which it declined by
      almost 50%. Continents show different patterns over time, with the global peak in
      2000 mainly explained by the USA and Europe, while Asia shows a stable number of
      >1000 per year. Nine countries together account for 98.9% of the total number of
      genetic patent applications. In The Netherlands, 26.7% of the genetic patent
      applications originate from public research institutions. After the year 2000,
      the number of genetic patent applications dropped significantly. Academic
      leadership and policy as well as patent regulations seem to have an important
      role in the trend differences. The ongoing investment in genetic research in the
      past decade is not reflected by an increase of patent applications. 

PMID- 24448545
TI  - Variation and association to diabetes in 2000 full mtDNA sequences mined from an
      exome study in a Danish population.
AB  - In this paper, we mine full mtDNA sequences from an exome capture data set of
      2000 Danes, showing that it is possible to get high-quality full-genome sequences
      of the mitochondrion from this resource. The sample includes 1000 individuals
      with type 2 diabetes and 1000 controls. We characterise the variation found in
      the mtDNA sequence in Danes and relate the variation to diabetes risk as well as
      to several blood phenotypes of the controls but find no significant associations.
      We report 2025 polymorphisms, of which 393 have not been reported previously.
      These 393 mutations are both very rare and estimated to be caused by very recent
      mutations but individuals with type 2 diabetes do not possess more of these
      variants. Population genetics analysis using Bayesian skyline plot shows a recent
      history of rapid population growth in the Danish population in accordance with
      the fact that >40% of variable sites are observed as singletons. 

PMID- 24448547
TI  - Accuracy of imputation to infer unobserved APOE epsilon alleles in genome-wide
      genotyping data.
AB  - Apolipoprotein E, encoded by APOE, is the main apoprotein for catabolism of
      chylomicrons and very low density lipoprotein. Two common single-nucleotide
      polymorphisms (SNPs) in APOE, rs429358 and rs7412, determine the three epsilon
      alleles that are established genetic risk factors for late-onset Alzheimer's
      disease (AD), cerebral amyloid angiopathy, and intracerebral hemorrhage (ICH).
      These two SNPs are not present in most commercially available genome-wide
      genotyping arrays and cannot be inferred through imputation using HapMap
      reference panels. Therefore, these SNPs are often separately genotyped.
      Introduction of reference panels compiled from the 1000 Genomes project has made
      imputation of these variants possible. We compared the directly genotyped and
      imputed SNPs that define the APOE epsilon alleles to determine the accuracy of
      imputation for inference of unobserved epsilon alleles. We utilized genome-wide
      genotype data obtained from two cohorts of ICH and AD constituting subjects of
      European ancestry. Our data suggest that imputation is highly accurate, yields an
      acceptable proportion of missing data that is non-differentially distributed
      across case and control groups, and generates comparable results to genotyped
      data for hypothesis testing. Further, we explored the effect of imputation
      algorithm parameters and demonstrated that customization of these parameters
      yields an improved balance between accuracy and missing data for inferred
      genotypes. 

PMID- 24448548
TI  - Fragile X syndrome due to a missense mutation.
AB  - Fragile X syndrome is a common inherited form of intellectual disability and
      autism spectrum disorder. Most patients exhibit a massive CGG-repeat expansion
      mutation in the FMR1 gene that silences the locus. In over two decades since the
      discovery of FMR1, only a single missense mutation (p.(Ile304Asn)) has been
      reported as causing fragile X syndrome. Here we describe a 16-year-old male
      presenting with fragile X syndrome but without the repeat expansion mutation.
      Rather, we find a missense mutation, c.797G>A, that replaces glycine 266 with
      glutamic acid (p.(Gly266Glu)). The Gly266Glu FMR protein abolished many
      functional properties of the protein. This patient highlights the diagnostic
      utility of FMR1 sequencing. 

PMID- 24448550
TI  - Coverage and efficiency in current SNP chips.
AB  - To answer the question as to which commercial high-density SNP chip covers most
      of the human genome given a fixed budget, we compared the performance of 12 chips
      of different sizes released by Affymetrix and Illumina for the European, Asian,
      and African populations. These include Affymetrix' relatively new population
      optimized arrays, whose SNP sets are each tailored toward a specific ethnicity.
      Our evaluation of the chips included the use of two measures, efficiency and cost
      benefit ratio, which we developed as supplements to genetic coverage. Unlike
      coverage, these measures factor in the price of a chip or its substitute size
      (number of SNPs on chip), allowing comparisons to be drawn between differently
      priced chips. In this fashion, we identified the Affymetrix population-optimized
      arrays as offering the most cost-effective coverage for the Asian and African
      population. For the European population, we established the Illumina Human Omni
      2.5-8 as the preferred choice. Interestingly, the Affymetrix chip tailored toward
      an Eastern Asian subpopulation performed well for all three populations
      investigated. However, our coverage estimates calculated for all chips proved
      much lower than those advertised by the producers. All our analyses were based on
      the 1000 Genome Project as reference population. 

PMID- 24448549
TI  - Systematic large-scale study of the inheritance mode of Mendelian disorders
      provides new insight into human diseasome.
AB  - One important piece of information about the human Mendelian disorders is the
      mode of inheritance. Recent studies of human genetic diseases on a large scale
      have provided many novel insights into the underlying molecular mechanisms.
      However, most successful analyses ignored the mode of inheritance of diseases,
      which severely limits our understanding of human disease mechanisms relating to
      the mode of inheritance at the large scale. Therefore, we here conducted a
      systematic large-scale study of the inheritance mode of Mendelian disorders, to
      bring new insight into human diseases. Our analyses include the comparison
      between dominant and recessive disease genes on both genomic and proteomic
      characteristics, Mendelian mutations, protein network properties and disease
      connections on both the genetic and the population levels. We found that dominant
      disease genes are more functionally central, topological central and more
      sensitive to disease outcome. On the basis of these findings, we suggested that
      dominant diseases should have higher genetic heterogeneity and should have more
      comprehensive connections with each other compared with recessive diseases, a
      prediction we confirm by disease network and disease comorbidity. 

PMID- 24448551
TI  - Substitution versus redox reactions of gold(III) complexes with L-cysteine, L
      methionine and glutathione.
AB  - The influence of tridentate, nitrogen donor ligands, on the stability of
      gold(III) complexes under physiological conditions was investigated. The
      interaction of [Au(terpy)Cl](2+) (terpy = 2,2':6'2'' terpyridine),
      [Au(bpma)Cl](2+) (bpma = bis(pyridyl-methyl)amine), [Au(dien)Cl](2+) (dien =
      diethylenetriamine) and [AuCl4](-) with the biologically relevant thiols, L
      cysteine (L-Cys) and glutathione (GSH), and thioether, L-methionine (L-Met), was
      studied using UV-Vis spectroscopy, cyclic voltammetry, (1)H NMR spectroscopy and
      ESI-MS. In this study, the rate constants for substitution reactions between
      monofunctional gold(III) complexes and sulfur donor ligands in aqueous solution
      were determined at different initial concentrations of reactants, chloride ions,
      pH and constant ionic strength. The obtained second-order rate constants for the
      reaction with L-methionine in the absence of added chloride at pH 2.5 and 25 
      degrees C follow the sequence (7.5 +/- 0.4) * 10(3) > (4.5 +/- 0.1) * 10(2) >
      88.3 +/- 0.8 M(-1) s(-1) for the terpy, bpma and dien complexes, respectively,
      demonstrating that the substitution step could be detected prior to the reduction
      step. This behavior was expected due to the influence of a decreasing pi-donor
      ability of the chelate ligands, which slows down the substitution reactions along
      the series of complexes studied. In order to throw more light on the mechanism of
      biological activity of gold(iii) compounds, such a systematic study was performed
      for all the mentioned thiols and thioether.

PMID- 24448552
TI  - Lysine-specific demethylase 1 regulates differentiation onset and migration of
      trophoblast stem cells.
AB  - Propagation and differentiation of stem cell populations are tightly regulated to
      provide sufficient cell numbers for tissue formation while maintaining the stem
      cell pool. Embryonic parts of the mammalian placenta are generated from
      differentiating trophoblast stem cells (TSCs) invading the maternal decidua. Here
      we demonstrate that lysine-specific demethylase 1 (Lsd1) regulates
      differentiation onset of TSCs. Deletion of Lsd1 in mice results in the reduction
      of TSC number, diminished formation of trophectoderm tissues and early embryonic
      lethality. Lsd1-deficient TSCs display features of differentiation initiation,
      including alterations of cell morphology, and increased migration and invasion.
      We show that increased TSC motility is mediated by the premature expression of
      the transcription factor Ovol2 that is directly repressed by Lsd1 in
      undifferentiated cells. In summary, our data demonstrate that the epigenetic
      modifier Lsd1 functions as a gatekeeper for the differentiation onset of TSCs,
      whereby differentiation-associated cell migration is controlled by the
      transcription factor Ovol2. 

PMID- 24448553
TI  - nBu4NI-catalyzed oxidative imidation of ketones with imides: synthesis of alpha
      amino ketones.
AB  - nBu4NI-Catalyzed oxidative imidation of ketones and imides for the synthesis of
      alpha-amino ketones were realized for the first time. The methodology is
      characterized by its wide substrate scope even for acetone with readily available
      phthalimide, saccharin and succinimide, which opens a new pathway for direct
      imidation of ketones. 

PMID- 24448554
TI  - Fecal microbiota imbalance in Mexican children with type 1 diabetes.
AB  - Dysbiosis of the intestinal microbiota affecting the gut barrier could be
      triggering Type 1 Diabetes (T1D), the second most frequent autoimmune disease in
      childhood. This study compared the structure of the fecal microbiota in 29
      mestizo children aged 7-18 years, including 8 T1D at onset, 13 T1D after 2 years
      treatment, and 8 healthy controls. Clinical information was collected,
      predisposing haplotypes were determined; the fecal DNA was extracted, the V4
      region of the 16S rRNA gene amplified and 454-pyrosequenced. The newly diagnosed
      T1D cases had high levels of the genus Bacteroides (p < 0.004), whereas the
      control group had a gut microbiota dominated by Prevotella. Children with T1D
      treated for >=2 years had levels of Bacteroides and Prevotella compared to those
      of the control group. The gut microbiota of newly diagnosed T1D cases is altered,
      but whether it is involved in disease causation or is a consequence of host
      selection remains unclear. 

PMID- 24448555
TI  - Mechanism of cellular accumulation of an iridium(III) pentamethylcyclopentadienyl
      anticancer complex containing a C,N-chelating ligand.
AB  - The effect of replacement of the N,N-chelating ligand 1,10-phenanthroline (phen)
      in the Ir(III) pentamethylcyclopentadienyl (Cp*) complex [(eta(5)
      Cp*)(Ir)(phen)Cl](+) (2) with the C,N-chelating ligand 7,8-benzoquinoline (bq) to
      give [(eta(5)-Cp*)(Ir)(bq)Cl] (1) on the cytotoxicity of these Cp*Ir(III)
      complexes toward cancer cell lines was investigated. Complex 2 is inactive,
      similar to other Cp*Ir(III) complexes containing the N,N-chelating ligands. In
      contrast, a single atom change (C(-) for N) in the chelating N,N ligand resulted
      in potency in human ovarian carcinoma cisplatin-sensitive A2780 cells, and,
      strikingly, 1 is active in the cisplatin-resistant human breast cancer MCF-7 and
      A2780/cisR cells. Replacement of the N,N-chelating ligand with the C,N-chelating
      ligand gives rise to increased hydrophobicity, leading to higher cellular
      accumulation, higher DNA-bound iridium in cells and higher cytotoxicity. The
      pathways involved in cellular accumulation of 1 have been further explored and
      compared with conventional cisplatin. The results show that both energy
      independent passive diffusion and energy-dependent transport play a role in
      accumulation of 1. Further results were consistent with involvement of p
      glycoprotein, multidrug resistance-associated protein 1 and glutathione
      metabolism in the efflux of 1. In contrast, the internalization of 1 mediated by
      the endocytotic uptake pathway(s) seems less likely. Understanding the factors
      which contribute to the mechanism of cellular accumulation of this Ir(III)
      complex can now lead to the design of structurally similar metal complexes for
      antitumor chemotherapy.

PMID- 24448556
TI  - Extracellular enzyme profiling of Stenotrophomonas maltophilia clinical isolates.

PMID- 24448557
TI  - Spectroscopic investigation on the interaction of copper porphyrazines and
      phthalocyanine with human telomeric G-quadruplex DNA.
AB  - The G-quadruplex DNA is a novel target for anticancer drug discovery and many
      scientific groups are investigating interaction of small molecules with G
      quadruplex DNA to discover therapeutic agents for cancer. Here, interaction of a
      phthalocyanine (Cu(PcTs)) and two tetrapyridinoporphyrazines ([Cu(2,3
      tmtppa)](4+) and [Cu(3,4-tmtppa)](4+)) with Na(+) and K(+) forms of human
      telomeric G-quadruplex DNA has been investigated by spectroscopic techniques. The
      results indicated that interaction of the cationic porphyrazines is remarkably
      stronger than the anionic phthalocyanine and they presumably bind to the G
      quadruplex DNA through end-stacking. Fluorescent intercalator displacement assay
      implied the displacement ability of the complexes with thiazole orange. In
      addition, circular dichroism spectra of both quadruplex forms converge to the
      Na(+) isoform after binding to the porphyrazines. In conclusion, the
      porphyrazines as the complexes that bind to the G-quadruplex DNA, could be
      suitable candidates for further investigations about inhibition of telomerase
      enzyme. 

PMID- 24448558
TI  - Socio-ecological correlates of mental health among ethnic minorities in areas of
      political conflict: a study of Druze adolescents in Israel.
AB  - Children and youths living in areas of political conflict are at increased risk
      of mental health problems, but little is known about psychosocial adjustment
      among ethnic minorities living in war-afflicted settings. This cross-sectional
      study used an ecological approach to investigate the unique contributions of
      child, family/social, and minority related factors as well as traumatic exposure
      and perceived discrimination to the mental health of 167 Druze adolescents in
      Northern Israel. Outcome measures included participants' self-reported
      posttraumatic stress disorder symptoms, psychological distress, and emotional and
      behavioral problems. Adolescents reported high indirect exposure, moderate
      discrimination, strong ethnic identity and high religious involvement. Regression
      analyses showed that female gender, number of traumatic events, and perceived
      discrimination were associated with more severe mental health outcomes. In
      addition, low social support and high religious involvement predicted increased
      PTSD symptom severity, while stronger ethnic identity was associated with less
      emotional and behavioral problems. Findings are discussed in terms of the
      cultural characteristics of the Druze community and highlight the need to
      consider additional stressors, such as discrimination, when working with ethnic
      minority youth in conflict zones. 

PMID- 24448559
TI  - Early Activity in Broca's Area During Reading Reflects Fast Access to
      Articulatory Codes From Print.
AB  - Prior evidence for early activity in Broca's area during reading may reflect fast
      access to articulatory codes in left inferior frontal gyrus pars opercularis
      (LIFGpo). We put this hypothesis to test using a benchmark for articulatory
      involvement in reading known as the masked onset priming effect (MOPE). In masked
      onset priming, briefly presented pronounceable strings of letters that share an
      initial phoneme with subsequently presented target words (e.g., gilp-GAME)
      facilitate word naming responses compared with unrelated primes (dilp-GAME).
      Crucially, these priming effects only occur when the task requires articulation
      (naming), and not when it requires lexical decisions. A standard explanation of
      masked onset priming is that it reflects fast computation of articulatory output
      codes from letter representations. We therefore predicted 1) that activity in
      left IFG pars opercularis would be modulated by masked onset priming, 2) that
      priming-related modulation in LIFGpo would immediately follow activity in
      occipital cortex, and 3) that this modulation would be greater for naming than
      for lexical decision. These predictions were confirmed in a
      magnetoencephalography (MEG) priming study. MOPEs emerged in left IFG at ~100 ms
      posttarget onset, and the priming effects were more sustained when the task
      involved articulation. 

PMID- 24448560
TI  - Reinfection by untreated partners of people treated for Chlamydia trachomatis and
      Neisseria gonorrhoeae: mathematical modelling study.
AB  - OBJECTIVES: Reinfection after treatment for Chlamydia trachomatis or Neisseria
      gonorrhoeae reduces the effect of control interventions. We explored the impact
      of delays in treatment of current partners on the expected probability of
      reinfection of index cases using a mathematical model. METHODS: We used
      previously reported parameter distributions to calculate the probability that
      index cases would be reinfected by their untreated partners. We then assumed
      different delays between index case and partner treatment to calculate the
      probabilities of reinfection. RESULTS: In the absence of partner treatment, the
      medians of the expected reinfection probabilities are 19.4% (IQR 9.2-31.6%) for C
      trachomatis and 12.5% (IQR 5.6-22.2%) for N gonorrhoeae. If all current partners
      receive treatment 3 days after the index case, the expected reinfection
      probabilities are 4.2% (IQR 2.1-6.9%) for C trachomatis and 5.5% (IQR 2.6-9.5%)
      for N gonorrhoeae. CONCLUSIONS: Quicker partner referral and treatment can
      substantially reduce reinfection rates for C trachomatis and N gonorrhoeae by
      untreated partners. The formula we used to calculate reinfection rates can be
      used to inform the design of randomised controlled trials of novel partner
      notification technologies like accelerated partner therapy.

PMID- 24448561
TI  - Direct aortic transcatheter valve implantation via mini-thoracotomy using the
      Medtronic CoreValve.
AB  - Transcatheter aortic valve implantation using the Medtronic CoreValve is a well
      established procedure. Although previously carried out only through the common
      femoral artery, today it is possible to perform the procedure through different
      arterial alternative access sites. A direct aortic approach through the ascending
      aorta could be carried out via a right anterior mini-thoracotomy in the second
      intercostal space. The pericardium is opened to expose the aorta. Two purse
      string sutures are then placed on the ascending aorta and a standard retrograde
      CoreValve implantation is performed with the standard delivery system.
      Advantages, contraindications, surgical technique and results are discussed.

PMID- 24448562
TI  - UK government vows to monitor waiting times for mental health services in new
      strategy.

PMID- 24448563
TI  - Influence of Holocene environmental change and anthropogenic impact on the
      diversity and distribution of roe deer.
AB  - Extant patterns of population structure and levels of diversity are a consequence
      of factors that vary in both space and time. Our objective in this study is to
      investigate a species that has responded to both natural and anthropogenic
      changes in ways that have shaped modern populations and provide insight into the
      key processes. The roe deer (Capreolus capreolus) is one of the two species of
      deer native to Britain. During the last glacial maximum (LGM), the British
      habitat was largely under ice and there was a land bridge to mainland Europe. As
      the Earth warmed during the early Holocene, the land bridge was lost. Subsequent
      hunting on the British mainland left the southern region extirpated of roe deer,
      whereas a refugial population remained in the north. Later reintroductions from
      Europe led to population expansion, especially in southern United Kingdom. Here,
      we combine data from ancient and modern DNA to track population dynamics and
      patterns of connectivity, and test hypotheses about the influence of natural and
      anthropogenic environmental change. We find that past expansion and divergence
      events coincided with a warming environment and the subsequent closure of the
      land bridge between Europe and the United Kingdom. We also find turnover in
      British roe deer haplotypes between the late-Holocene and modern day that have
      likely resulted from recent human disturbance activities such as habitat
      perturbation, overhunting and restocking. 

PMID- 24448564
TI  - Landscape models for nuclear genetic diversity and genetic structure in white
      footed mice (Peromyscus leucopus).
AB  - Dramatic changes in the North American landscape over the last 12 000 years have
      shaped the genomes of the small mammals, such as the white-footed mouse
      (Peromyscus leucopus), which currently inhabit the region. However, very recent
      interactions of populations with each other and the environment are expected to
      leave the most pronounced signature on rapidly evolving nuclear microsatellite
      loci. We analyzed landscape characteristics and microsatellite markers of P.
      leucopus populations along a transect from southern Ohio to northern Michigan, in
      order to evaluate hypotheses about the spatial distribution of genetic
      heterogeneity. Genetic diversity increased to the north and was best approximated
      by a single-variable model based on habitat availability within a 0.5-km radius
      of trapping sites. Interpopulation differentiation measured by clustering
      analysis was highly variable and not significantly related to latitude or habitat
      availability. Interpopulation differentiation measured as FST values and chord
      distance was correlated with the proportion of habitat intervening, but was best
      explained by agricultural distance and by latitude. The observed gradients in
      diversity and interpopulation differentiation were consistent with recent habitat
      availability being the major constraint on effective population size in this
      system, and contradicted the predictions of both the postglacial expansion and
      core-periphery hypotheses. 

PMID- 24448565
TI  - Uveal effusion as a mechanism of bilateral angle-closure glaucoma induced by
      chlorthalidone.
AB  - PURPOSE: To report a novel case of acute bilateral uveal effusions, angle
      closure, and acute myopia induced by administration of chlorthalidone. METHODS:
      Case report. RESULTS: Bilateral shallow anterior chambers, high intraocular
      pressure, and a myopic shift were encountered in a patient 1 week after
      initiation of chlorthalidone. Ultrasound evaluation revealed bilateral
      ciliochoroidal effusions, appositional angle closure, and suspected ciliary body
      edema. Cessation of chlorthalidone, in addition to administration of cycloplegics
      and ocular antihypertensives, resulted in prompt resolution of this idiosyncratic
      reaction. CONCLUSIONS: The antihypertensive medication chlorthalidone may cause
      bilateral uveal effusions inducing acute angle-closure glaucoma and acute myopia.

PMID- 24448566
TI  - Peptide-based FeS4 complexes: the zinc ribbon fold is unsurpassed to stabilize
      both the FeII and FeIII states.
AB  - Whereas Zn(Cys)4 zinc fingers exist with different protein folds, only the zinc
      ribbon fold is found in rubredoxin Fe(Cys)4 sites. To assess the significance of
      this observation, we have investigated the binding and stability of Fe(2+) and
      Fe(3+) ions by a set of four peptides designed to model Zn(Cys)4 zinc fingers
      with various folds, i.e. zinc ribbon, treble clef and a loosened zinc ribbon
      fold. All peptides were shown by means of UV-Vis and CD spectroscopies to form
      stable 1 : 1 Fe(II)/peptide complexes with binding constants higher than 10(7) M(
      1) at pH 7. Their oxidation into Fe(III) complexes and the stability of the
      latter were compared. The UV-Vis absorption and CD spectroscopic properties of
      the Fe(II) and Fe(III) complexes were analysed with respect to the structures of
      the zinc analogues in order to get insight into the local arrangement of the
      Fe(Cys)4 core around the metal ion. The chemical stability of these complexes was
      rationalized according to the shielding from the solvent provided by the various
      peptide folds to the FeS4 core. In addition, we showed that whereas UV-visible
      spectra inform only on the FeS4, the information derived from the corresponding
      CD spectra extend to the Cbeta orientation and the peptide fold. The results
      presented here demonstrate that while the zinc ribbon fold is not strictly
      required to obtain a Fe(Cys)4 site, it affords a drastically superior protection
      of the site toward external redox agents. This finding brings new clues to
      engineer stable and redox-active Fe(Cys)4 sites in de novo proteins. 

PMID- 24448567
TI  - New dimensions in immunology.

PMID- 24448568
TI  - Quantitative shotgun proteomics: considerations for a high-quality workflow in
      immunology.

PMID- 24448570
TI  - Single-cell technologies for monitoring immune systems.
AB  - The complex heterogeneity of cells, and their interconnectedness with each other,
      are major challenges to identifying clinically relevant measurements that reflect
      the state and capability of the immune system. Highly multiplexed, single-cell
      technologies may be critical for identifying correlates of disease or
      immunological interventions as well as for elucidating the underlying mechanisms
      of immunity. Here we review limitations of bulk measurements and explore advances
      in single-cell technologies that overcome these problems by expanding the depth
      and breadth of functional and phenotypic analysis in space and time. The
      geometric increases in complexity of data make formidable hurdles for exploring,
      analyzing and presenting results. We summarize recent approaches to making such
      computations tractable and discuss challenges for integrating heterogeneous data
      obtained using these single-cell technologies. 

PMID- 24448571
TI  - TCR signaling: the barrier within.

PMID- 24448569
TI  - Unifying immunology with informatics and multiscale biology.
AB  - The immune system is a highly complex and dynamic system. Historically, the most
      common scientific and clinical practice has been to evaluate its individual
      components. This kind of approach cannot always expose the interconnecting
      pathways that control immune-system responses and does not reveal how the immune
      system works across multiple biological systems and scales. High-throughput
      technologies can be used to measure thousands of parameters of the immune system
      at a genome-wide scale. These system-wide surveys yield massive amounts of
      quantitative data that provide a means to monitor and probe immune-system
      function. New integrative analyses can help synthesize and transform these data
      into valuable biological insight. Here we review some of the computational
      analysis tools for high-dimensional data and how they can be applied to
      immunology. 

PMID- 24448572
TI  - Old HDL learns a new (anti-inflammatory) trick.

PMID- 24448573
TI  - Strength in numbers: comparing vaccine signatures the modular way.

PMID- 24448585
TI  - Iron(III)-mediated photocatalytic selective substitution of aryl bromine by
      chlorine with high chloride utilization efficiency.
AB  - An iron(iii)-mediated photocatalytic method for the conversion of aryl,
      heteroaryl and polycyclic aromatic bromides to the corresponding chlorides with
      high selectivity has been achieved successfully. The mild reaction conditions and
      high chloride utilization efficiency promise a bright future for chlorination
      reactions. 

PMID- 24448586
TI  - A highly reversible lithium metal anode.
AB  - Lithium metal has shown a lot of promise for use as an anode material in
      rechargeable batteries owing to its high theoretical capacity. However, it does
      not meet the cycle life and safety requirements of rechargeable batteries owing
      to electrolyte decomposition and dendrite formation on the surfaces of the
      lithium anodes during electrochemical cycling. Here, we propose a novel
      electrolyte system that is relatively stable against lithium metal and mitigates
      dendritic growth. Systematic design methods that combined simulations, model
      based experiments, and in situ analyses were employed to design the system. The
      reduction potential of the solvent, the size of the salt anions, and the
      viscosity of the electrolyte were found to be critical parameters determining the
      rate of dendritic growth. A lithium metal anode in contact with the designed
      electrolyte exhibited remarkable cyclability (more than 100 cycles) at a high
      areal capacity of 12 mAh cm(-2). 

PMID- 24448587
TI  - An agonistic anti-BTLA mAb (3C10) induced generation of IL-10-dependent
      regulatory CD4+ T cells and prolongation of murine cardiac allograft.
AB  - BACKGROUND: The co-inhibitory receptor B and T lymphocyte attenuator (BTLA) has
      been implicated in the regulation of autoimmunity and may potentially play an
      important role in allograft tolerance. This study investigated the effect of an
      agonistic anti-BTLA mAb (3C10) in the fully major histocompatibility complex
      mismatched murine cardiac transplantation. METHODS: CBA mice underwent
      transplantation of C57BL/6 hearts and received one dose of 3C10 on the day of
      transplantation (day 0) or four doses of 3C10 on day 0, 3, 6, and 9. Adoptive
      transfer studies were performed to determine whether regulatory cells were
      generated. Moreover, to confirm the requirement for regulatory T cell and Th-2
      cytokines, anti-interleukin (IL)-2 receptor alpha antibody (PC-61) or anti-IL-10
      antibody (JES-2A5) was administered to a 3C10-treated CBA recipient. RESULTS: CBA
      mice treated with one and four doses of 3C10 prolonged allograft survival (median
      survival times [MSTs], 43 and >100 days, respectively). Secondary CBA recipients
      given whole splenocytes or CD4 cells from primary 3C10-treated CBA recipients had
      significantly prolonged survival of C57BL/6 hearts (MSTs, >100 in both). Also,
      flow cytometry studies showed an increased CD4CD25Foxp3 cell population in 3C10
      treated mice. Additionally, IL-2 and interferon-gamma production were suppressed
      in 3C10-treated mice, and IL-4 and IL-10 from 3C10-treated CBA mice increased.
      Moreover, 3C10 directly suppressed alloproliferation in a mixed leukocyte
      culture. However, administration of PC-61 or JES-2A5 clearly attenuated prolonged
      survival of 3C10-treated mice (MSTs, 15.5 and 13.5 days, respectively).
      CONCLUSION: 3C10 could control acute rejection by its suppressive effect on
      alloreactive T cells and induction of IL-10-dependent regulatory CD4 T cells.

PMID- 24448588
TI  - Summary of the British Transplantation Society guidelines for transplantation
      from donors after deceased circulatory death.
AB  - The second edition of the British Transplantation Society Guidelines for
      Transplantation from Donors after Deceased Circulatory Death was published in
      June 2013. The guideline has been extensively revised since the previous edition
      in 2004 and has used the GRADE system to rate the strength of evidence and
      recommendations. This article summarizes the Statements of Recommendation
      contained in the guideline, which provide a framework for transplantation after
      deceased circulatory death in the U.K. and may be of wide international interest.
      It is recommended that the full guideline document is consulted for details of
      the relevant references and evidence base. This may be accessed at:
      http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Gui
      elines.aspx.

PMID- 24448589
TI  - Targeting PGC-1alpha to overcome the harmful effects of glucocorticoids in
      porcine neonatal pancreas cell clusters.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma-coactivator-1alpha
      (PGC-1alpha) has recently been implicated as a crucial factor in the
      glucocorticoid-suppressed expansion and transdifferentiation of porcine neonatal
      pancreatic cell clusters (NPCCs). However, the molecular mechanism has not been
      clarified. METHODS: We investigated whether the suppression of PGC-1alpha
      expression protects against beta-cell dysfunction induced by dexamethasone (Dx)
      treatment in vitro and in vivo and determined the mechanism of action of PGC
      1alpha in porcine NPCCs. RESULTS: The reduction in Pdx-1 gene expression caused
      by either Dx treatment or PGC-1alpha overexpression was normalized by siPGC
      1alpha. Nuclear FOXO1 and cytoplasmic Pdx-1 were detected after Dx treatment.
      However, FOXO1 was observed in the cytoplasm, and Pdx-1 was observed in the
      nucleus after siPGC-1alpha. Suppression of PGC-1alpha by siPGC-1alpha improved
      the Dx-induced repression of insulin secretion and insulin content. In vivo
      studies showed that the glucose level in the Ad-siPGC-1alpha-infected group was
      significantly lower than that in the Dx-treated group. Insulin expression in the
      graft tissue disappeared in the Dx-injected group. However, the siPGC-1alpha- and
      Dx-treated group showed increased insulin expression and an increase in graft
      mass, beta-cell mass, and beta-cell % in the graft. Conversely, the Dx-induced
      ductal cystic area was markedly reduced in the siPGC-1alpha- and Dx-treated
      group. CONCLUSIONS: Our results suggest that the transdifferentiation of porcine
      NPCCs into beta cells is influenced by the duration of the Dx treatment, which
      might result from the suppression of key pancreatic transcription factors. PGC
      1alpha is an attractive target for modulating the deleterious effects of
      glucocorticoids on pancreatic stem cells.

PMID- 24448590
TI  - Multi-stimuli responsive self-healing metallo-hydrogels: tuning of the gel
      recovery property.
AB  - A series of amphiphilic tyrosine based self-healable, multi-stimuli responsive
      metallo-hydrogels have been discovered. Formation of these hydrogels is highly
      selective to Ni(2+) ions. The self-healing property and the stiffness of these
      metallo-hydrogels can be tuned by varying the chain length of the corresponding
      gelator amphiphile. 

PMID- 24448591
TI  - Preparation, blood coagulation and cell compatibility evaluation of chitosan
      graft-polylactide copolymers.
AB  - Biodegradable chitosan-graft-polylactide (PLA-CS) copolymers were prepared by the
      grafting of a poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) precursor to the
      backbone of chitosan using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      hydrochloride (EDC ? HCl) and N-hydroxysuccinimide (NHS) as a coupling agent. The
      blood and cell compatibility of the graft copolymers were investigated in
      comparison to PLLA and PDLA homopolymers. The coagulation properties of PLA-CS
      were evaluated by hemolysis, plasma recalcification, dynamic blood clotting and
      protein absorption assays. PLA-CS copolymers present similar hemolysis ratio and
      plasma recalcification time as PLA, but slower dynamic blood clotting and lower
      protein absorption. The cell viability was assessed by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT), agar diffusion and lactate
      dehydrogenase (LDH) experiments. All the samples presented no effect on the
      viability to cells. Inflammatory cytokine analysis using sandwich ELISAs revealed
      that PLA-CS would not stimulate inflammatory activity.

PMID- 24448592
TI  - Combined deletions of amyloid precursor protein and amyloid precursor-like
      protein 2 reveal different effects on mouse brain metal homeostasis.
AB  - Alterations to the expression of the Amyloid Precursor Protein (APP) and its
      paralogue Amyloid Precursor-Like Protein 2 (APLP2) affect metal homeostasis in
      vitro and in vivo. Analysis of the in vivo effects of the APP and APLP2 knockouts
      on metal homeostasis has been restricted to APP and APLP2 single knockout mice,
      and up to12 month old animals. To define the redundancy and inter-relationship
      between the APP and APLP2 genes as regulators of metal homeostasis, and how this
      is influenced by aging, we investigated copper, iron, zinc and manganese levels
      in APP and APLP2 single knockout mice as well as homozygous:hemizygous knockout
      mice at 3, 12 and 18 plus months of age. These studies identified age and
      genotype dependent changes in metal levels, and established differences in the
      relative roles played by APP and APLP2 in modulating metal homeostasis. 

PMID- 24448593
TI  - Enhanced low-latency detection of motor intention from EEG for closed-loop brain
      computer interface applications.
AB  - In recent years, the detection of voluntary motor intentions from
      electroencephalogram (EEG) has been used for triggering external devices in
      closed-loop brain-computer interface (BCI) research. Movement-related cortical
      potentials (MRCP), a type of slow cortical potentials, have been recently used
      for detection. In order to enhance the efficacy of closed-loop BCI systems based
      on MRCPs, a manifold method called Locality Preserving Projection, followed by a
      linear discriminant analysis (LDA) classifier (LPP-LDA) is proposed in this paper
      to detect MRCPs from scalp EEG in real time. In an online experiment on nine
      healthy subjects, LPP-LDA statistically outperformed the classic matched filter
      approach with greater true positive rate (79 +/- 11% versus 68 +/- 10%; p =
      0.007) and less false positives (1.4 +/- 0.8/min versus 2.3 +/- 1.1/min; p =
      0.016 ). Moreover, the proposed system performed detections with significantly
      shorter latency (315 +/- 165 ms versus 460 +/- 123 ms; p = 0.013), which is a
      fundamental characteristics to induce neuroplastic changes in closed-loop BCIs,
      following the Hebbian principle. In conclusion, the proposed system works as a
      generic brain switch, with high accuracy, low latency, and easy online
      implementation. It can thus be used as a fundamental element of BCI systems for
      neuromodulation and motor function rehabilitation.

PMID- 24448594
TI  - Influences of interpolation error, electrode geometry, and the electrode-tissue
      interface on models of electric fields produced by deep brain stimulation.
AB  - Deep brain stimulation (DBS) is an established therapy for movement disorders,
      but the fundamental mechanisms by which DBS has its effects remain unknown.
      Computational models can provide insights into the mechanisms of DBS, but to be
      useful, the models must have sufficient detail to predict accurately the electric
      fields produced by DBS. We used a finite-element method model of the Medtronic
      3387 electrode array, coupled to cable models of myelinated axons, to quantify
      how interpolation errors, electrode geometry, and the electrode-tissue interface
      affect calculation of electrical potentials and stimulation thresholds for
      populations of model nerve fibers. Convergence of the potentials was not a
      sufficient criterion for ensuring the same degree of accuracy in subsequent
      determination of stimulation thresholds, because the accuracy of the stimulation
      thresholds depended on the order of the elements. Simplifying the 3387 electrode
      array by ignoring the inactive contacts and extending the terminated end of the
      shaft had position-dependent effects on the potentials and excitation thresholds,
      and these simplifications may impact correlations between DBS parameters and
      clinical outcomes. When the current density in the bulk tissue is uniform, the
      effect of the electrode-tissue interface impedance could be approximated by
      filtering the potentials calculated with a static lumped electrical equivalent
      circuit. Further, for typical DBS parameters during voltage-regulated
      stimulation, it was valid to approximate the electrode as an ideal polarized
      electrode with a nonlinear capacitance. Validation of these computational
      considerations enables accurate modeling of the electric field produced by DBS. 

PMID- 24448595
TI  - First in vivo potassium-39 (39K) MRI at 9.4 T using conventional copper radio
      frequency surface coil cooled to 77 K.
AB  - Potassium-39 ((39)K) magnetic resonance imaging (MRI) is a noninvasive technique
      which could potentially allow for detecting intracellular physiological
      variations in common human pathologies such as stroke and cancer. However, the
      low signal-to-noise ratio (SNR) achieved in (39)K-MR images hampered data
      acquisition with sufficiently high spatial and temporal resolution in animal
      models so far. Full wave electromagnetic (EM) simulations were performed for a
      single-loop copper (Cu) radio frequency (RF) surface resonator with a diameter of
      30 mm optimized for rat brain imaging at room temperature (RT) and at liquid
      nitrogen (LN2) with a temperature of 77 K. A novel cryogenic Cu RF surface
      resonator with home-built LN2 nonmagnetic G10 fiberglass cryostat system for
      small animal scanner at 9.4 T was designed, built and tested in phantom and in in
      vivo MR measurements. Aerogel was used for thermal insulation in the developed
      LN2 cryostat. In this paper, we present the first in vivo (39)K-MR images at 9.4
      T for both healthy and stroke-induced rats using the developed cryogenic coil at
      77 K. In good agreement with EM-simulations and bench-top measurements, the
      developed cryogenic coil improved the SNR by factor of 2.7 +/- 0.2 in both
      phantom and in in vivo MR imaging compared with the same coil at RT.

PMID- 24448596
TI  - Monte Carlo bias field correction in endorectal diffusion imaging.
AB  - Prostate cancer is one of the leading causes of cancer death in the male
      population. The detection of prostate cancer using imaging has been challenging
      until recently. Multiparametric magnetic resonance imaging (MRI) has been shown
      to allow accurate localization of the cancers and can help direct biopsies to
      cancer foci, which is required to plan the treatment. The interpretation of MRI,
      however, requires a high level of expertise and review of large multiparametric
      datasets. An endorectal receiver coil is often used to improve signal-to-noise
      ratio and aid in detection of smaller cancer foci. Moreover, computed high b
      value diffusion-weighted imaging show improved delineation of tumors but is
      subject to strong bias fields near the coil. Here, a nonparametric approach to
      bias field correction for endorectal diffusion imaging via Monte Carlo sampling
      is introduced. It will be shown that the delineation between the prostate gland
      and the background and intensity inhomogeneity may be improved using the proposed
      approach. High b-value generated results also show improved visualization of
      tumor regions. The results suggest that Monte Carlo bias correction may have
      potential as a preprocessing tool for endorectal diffusion images for the
      prostate cancer detection and localization or segmentation. 

PMID- 24448597
TI  - Impaired taste and increased mortality in acutely hospitalized older people.
AB  - Taste ability is known to be impaired in elderly and even more so in acutely
      hospitalized elderly people. To our knowledge, no study has investigated the
      association between taste impairment and mortality. Our aim was to examine this
      association in acutely hospitalized older people. In a prospective study, 200
      acutely hospitalized elderly people >=70 years of age were included between
      November 2009 and October 2010 at the Oslo University Hospital, Norway. Exclusion
      criteria were cognitive impairment, nursing home residency, and terminal
      diseases. Comorbidity was registered with the Cumulative Illness Rating Scale, in
      addition to recording of age, gender, smoking, education, and number of
      medications. Taste ability was assessed quantitatively with the "taste strips
      method" in 174 patients (mean age: 84 years). Mortality until 1 January 2012 was
      obtained from hospital records. Fifty-six patients died during the observation
      period. The relative risk of death in total taste score quartile 4 compared with
      total taste score quartile 1 was 0.31 (95% confidence interval [95% CI]: 0.14
      0.69, P = 0.004), after adjusting for age, gender, smoking, education, and
      Cumulative Illness Rating Scale. Adjusted 1-year mortality decreased from 30% in
      total taste score quartile 1 to 9% in total taste score quartile 4. Thus,
      impaired taste appears to be strongly associated with mortality in acutely
      hospitalized elderly people. 

PMID- 24448598
TI  - Parental smoking during pregnancy and total and abdominal fat distribution in
      school-age children: the Generation R Study.
AB  - OBJECTIVE: Fetal smoke exposure may influence growth and body composition later
      in life. We examined the associations of maternal and paternal smoking during
      pregnancy with total and abdominal fat distribution in school-age children.
      METHODS: We performed a population-based prospective cohort study among 5243
      children followed from early pregnancy onward in the Netherlands. Information
      about parental smoking was obtained by questionnaires during pregnancy. At the
      median age of 6.0 years (90% range: 5.7-7.4), we measured anthropometrics, total
      fat and android/gynoid fat ratio by dual-energy X-ray absorptiometry, and
      preperitoneal and subcutaneous abdominal fat were measured by ultrasound.
      RESULTS: The associations of maternal smoking during pregnancy were only present
      among girls (P-value for sex interaction<0.05). Compared with girls from mothers
      who did not smoke during pregnancy, those from mothers who smoked during the
      first trimester only had a higher android/gynoid fat ratio (difference 0.23 (95%
      confidence interval (CI): 0.09-0.37) s.d. scores (SDS). Girls from mothers who
      continued smoking throughout pregnancy had a higher body mass index (difference:
      0.24 (95% CI: 0.14-0.35) SDS), total fat mass (difference: 0.23 (95% CI: 0.14
      0.33) SDS), android/gynoid fat ratio (difference: 0.34 (95% CI: 0.22-0.46) SDS),
      subcutaneous abdominal fat (difference: 0.22 (95% CI: 0.11-0.33) SDS) and
      preperitoneal abdominal fat (difference: 0.20 (95% CI: 0.08-0.31) SDS). Similar
      associations with body fat distribution outcomes were observed for paternal
      smoking during pregnancy. Both continued maternal and paternal smoking during
      pregnancy may be associated with an increased risk of childhood overweight. The
      corresponding odds ratios were 1.19 (95% CI: 0.98-1.46) and 1.32 (1.10-1.58),
      respectively. CONCLUSIONS: Maternal and paternal smoking during pregnancy are
      associated with an adverse body and abdominal fat distribution and increased risk
      of overweight in children. Similar effects of maternal and paternal smoking
      suggest that direct intrauterine mechanisms and common family-based lifestyle
      related factors explain the associations.

PMID- 24448600
TI  - Thr130Ile polymorphism of HNF4A gene is associated with gestational diabetes
      mellitus in Mexican population.
AB  - Hepatocyte nuclear factor 4alpha (HNF4A) is a transcription factor that regulates
      the expression of genes in the liver, pancreas, kidney, intestine, and other
      tissues. Previous studies in the Mexican population have shown a high frequency
      of the Thr130Ile polymorphism and have suggested its important role in the
      pathogenesis of early-onset type 2 diabetes. The aim of the present study was to
      determine whether this variant also contributes to gestational diabetes mellitus
      (GDM) in a Mexican population. We studied 213 unrelated postpartum women and
      their neonates, who were divided into 2 groups: control and GDM. The control
      group was formed by 108 healthy postpartum women and their neonates, and the GDM
      group was formed by 105 postpartum women diagnosed with GDM and their neonates.
      All subjects were genotyped for the Thr130Ile polymorphism in HNF4A by Taqman
      allelic discrimination assays and sequencing. Our results showed a higher
      frequency of the minor allele of the Thr130Ile polymorphism in the GDM group
      compared with the control group (P = 0.0452; odds ratio, 2.59; 95% confidence
      interval, 1.02-6.59). With respect to offspring, the frequency of the
      polymorphism was higher in the offspring of the GDM group than in the offspring
      of the control group; however, no significant differences between the groups were
      observed (P = 0.2551; odds ratio, 1.90; 95% confidence interval, 0.99-3.64). The
      findings suggest that the Thr130Ile polymorphism is associated with GDM in the
      studied Mexican population. 

PMID- 24448599
TI  - Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys:
      pathomechanistic role of peripheral sympathetic system and neuropeptide Y.
AB  - The purpose of this article is to characterize skin lesions in cynomolgus monkeys
      following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral
      vildagliptin administration caused dose-dependent and reversible blister
      formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores
      involving the extremities at >=5 mg/kg/day and necrosis of the tail and the
      pinnae at >=80 mg/kg/day after 3 weeks of treatment. At the affected sites, the
      media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia.
      Skin lesion formation was prevented by elevating ambient temperature.
      Vildagliptin treatment also produced an increase in blood pressure and heart rate
      likely via increased sympathetic tone. Following treatment with vildagliptin at
      80 mg/kg/day, the recovery time after lowering the temperature in the feet of
      monkeys and inducing cold stress was prolonged. Ex vivo investigations showed
      that small digital arteries from skin biopsies of vildagliptin-treated monkeys
      exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding
      correlated with a specific increase in NPY and in NPY1 receptors observed in the
      skin of vildagliptin-treated monkeys. Present data provide evidence that skin
      effects in monkeys are of vascular origin and that the effects on the NPY system
      in combination with increased peripheral sympathetic tone play an important
      pathomechanistic role in the pathogenesis of cutaneous toxicity. 

PMID- 24448601
TI  - Clinical implications of the interleukin 27 serum level in breast cancer.
AB  - INTRODUCTION: Interleukin 27 (IL-27), belonging to the IL-12 family, exerts a
      critical role in immune regulation of infection, autoimmunity, and tumor. In this
      study, we aimed to investigate the roles of IL-27 and vascular endothelial growth
      factor (VEGF) in breast cancer. METHODS: The serum levels of IL-27 and VEGF in
      150 patients with breast cancer and 90 control subjects were measured by an
      enzyme-linked immunosorbent assay. Estrogen receptor, progesterone receptor, and
      human epithelial growth factor receptor 2 were measured by immunohistochemistry.
      Clinical stage, tumor size, lymph node metastasis, grade, and histological type
      were also recorded. RESULTS: The serum levels of IL-27 and VEGF were
      significantly greater in breast cancer patients than in the control group. In
      addition, there was a significant correlation between IL-27 and VEGF, and serum
      IL-27 and VEGF levels were associated with the clinical stage of breast cancer.
      Moreover, the serum levels of IL-27 were especially elevated in breast cancer
      patients who were estrogen receptor-positive and progesterone receptor-positive.
      Furthermore, the serum levels of IL-27 and VEGF decreased after patients with
      breast cancer had modified radical mastectomy. CONCLUSION: Interleukin 27 may be
      a new prognostic biomarker of breast cancer and a promising target to limit both
      angiogenesis and tumor growth.

PMID- 24448602
TI  - Surface decoration of catanionic vesicles with superparamagnetic iron oxide
      nanoparticles: a model system for triggered release under moderate temperature
      conditions.
AB  - We report the design of new catanionic vesicles decorated with iron oxide
      nanoparticles, which could be used as a model system to illustrate controlled
      delivery of small solutes under mild hyperthermia. Efficient release of
      fluorescent dye rhodamine 6G was observed when samples were exposed to an
      oscillating magnetic field. Our system provides direct evidence for reversible
      permeability upon magnetic stimulation. 

PMID- 24448603
TI  - Evidence based medicine--an oral history.

PMID- 24448604
TI  - Spectrally interleaved, comb-mode-resolved spectroscopy using swept dual
      terahertz combs.
AB  - Optical frequency combs are innovative tools for broadband spectroscopy because a
      series of comb modes can serve as frequency markers that are traceable to a
      microwave frequency standard. However, a mode distribution that is too discrete
      limits the spectral sampling interval to the mode frequency spacing even though
      individual mode linewidth is sufficiently narrow. Here, using a combination of a
      spectral interleaving and dual-comb spectroscopy in the terahertz (THz) region,
      we achieved a spectral sampling interval equal to the mode linewidth rather than
      the mode spacing. The spectrally interleaved THz comb was realized by sweeping
      the laser repetition frequency and interleaving additional frequency marks. In
      low-pressure gas spectroscopy, we achieved an improved spectral sampling density
      of 2.5 MHz and enhanced spectral accuracy of 8.39 * 10(-7) in the THz region. The
      proposed method is a powerful tool for simultaneously achieving high resolution,
      high accuracy, and broad spectral coverage in THz spectroscopy.

PMID- 24448605
TI  - The synthesis and characterization of Ag-N dual-doped p-type ZnO: experiment and
      theory.
AB  - Ag-N dual-doped ZnO films have been fabricated by a chemical bath deposition
      method. The p-type conductivity of the dual-doped ZnO:(Ag, N) is stable over a
      long period of time, and the hole concentration in the ZnO:(Ag, N) is much higher
      than that in mono-doped ZnO:Ag or ZnO:N. We found that this is because AgZn-NO
      complex acceptors can be formed in ZnO:(Ag, N). First-principles calculations
      show that the complex acceptors generate a fully occupied band above the valance
      band maximum, so the acceptor levels become shallower and the hole concentration
      is increased. Furthermore, the binding energy of the Ag-N complex in ZnO is
      negative, so ZnO:(Ag, N) can be stable. These results indicate that the Ag-N dual
      doping may be expected to be a potential route to achieving high-quality p-type
      ZnO for use in a variety of devices. 

PMID- 24448606
TI  - Molecular tools for the construction of peptide-based materials.
AB  - Proteins and peptides are fundamental components of living systems where they
      play crucial roles at both functional and structural level. The versatile
      biological properties of these molecules make them interesting building blocks
      for the construction of bio-active and biocompatible materials. A variety of
      molecular tools can be used to fashion the peptides necessary for the assembly of
      these materials. In this tutorial review we shall describe five of the main
      techniques, namely solid phase peptide synthesis, native chemical ligation,
      Staudinger ligation, NCA polymerisation, and genetic engineering, that have been
      used to great effect for the construction of a host of peptide-based materials. 

PMID- 24448607
TI  - Osteogenetic property of a biodegradable three-dimensional macroporous hydrogel
      coating on titanium implants fabricated via EPD.
AB  - The potential for a successful integration of implants with surrounding tissue
      may be jeopardized in a number of compromised conditions. Biochemical surface
      modification is one of the choices to extend the spectrum of indications. We have
      previously successfully fabricated chitosan-gelatin (CS/G) coatings on a titanium
      surface via electrophoretic deposition, which may be promising candidates for
      further loading of functional agents. In this study, we have identified the
      microstructure, physicochemical properties and biological performance of CS/G
      coatings in vitro and in vivo. The in vitro degradation test indicated that CS/G
      coatings in the presence of lysozyme showed a significant weight loss after 28
      days. The results of the cell culture exhibited that CS/G coatings could sustain
      MC3T3-E1 cell attachment, proliferation and migration. In vivo osteogenetic
      behavior evaluated by Micro-CT and histomorphometrical analysis revealed
      significant new bone formation around CS/G implants at 8 and 12 weeks, compared
      to sandblasted/acid-etched implants. Moreover, histological evaluation suggested
      the majority of CS/G coatings were degraded at 12 weeks. Therefore, we have
      concluded that the three-dimensional porous structure of scaffold-like CS/G
      coatings may facilitate osteogenesis and that such coatings can be biodegraded in
      the early bone healing process.

PMID- 24448608
TI  - Highly porous structure strategy to improve the SnO2 electrode performance for
      lithium-ion batteries.
AB  - SnO2 is a promising high-capacity anode material for lithium-ion batteries
      (LIBs), but it usually exhibits poor cycling stability due to its huge volume
      variation during the lithium uptake and release process. In this work, SnO2
      nanofibers and nanotubes with highly porous (HPNFs, HPNTs) structure have been
      synthesized by a facile emulsion electrospinning and subsequent calcination
      process in air at 500  degrees C. Pores with a diameter range of 2-30 nm were
      distributed evenly on the surface of the nanofibers and nanotubes. The HPNFs and
      HPNTs manifested high capacities and excellent cycle performance as the anode
      electrode for LIBs, and they can deliver reversible capacities of 583 and 645 mA
      h g(-1) at a current density of 100 mA g(-1) after 50 cycles, respectively. When
      the current density is up to 5 A g(-1), the electrodes still exhibit a good
      retention, and the reversible capacities were about 370 and 432 mA h g(-1), which
      performs much better than the nanofibers and nanotubes without a porous
      structure. Our results demonstrated that this simple method could be extended for
      the synthesis of porous metal oxide nanotubes with high performances in the
      applications of lithium ion batteries and other fields. 

PMID- 24448609
TI  - The liquid phase epitaxy approach for the successful construction of ultra-thin
      and defect-free ZIF-8 membranes: pure and mixed gas transport study.
AB  - The liquid-phase epitaxy (LPE) method was effectively implemented to deliberately
      grow/construct ultrathin (0.5-1 MUm) continuous and defect-free ZIF-8 membranes.
      Permeation properties of different gas pair systems (O2-N2, H2-CO2, CO2-CH4, C3H6
      C3H8, CH4-n-C4H10) were studied using the time lag technique. 

PMID- 24448610
TI  - Context for WOC practice: strengthening the evidence base for ostomy care.

PMID- 24448611
TI  - 40 years of excellence: a review of incontinence literature in the WOCN Society's
      official publication.

PMID- 24448612
TI  - Turning and repositioning the critically ill patient with hemodynamic
      instability.

PMID- 24448613
TI  - Introducing the Cleveland Clinic WOC Nursing Hall of Fame.

PMID- 24448614
TI  - Selecting a tool for assessing health-related quality of life in ostomates.

PMID- 24448615
TI  - Pressure ulcer prevalence, use of preventive measures, and mortality risk in an
      acute care population: a quality improvement project.
AB  - The primary aim of this quality improvement project was to determine pressure
      prevalence, risk of mortality, and use of preventive measures in a group of
      hospitalized patients. Two hundred fifty-eight patients recruited from Skaraborg
      Hospital in Sweden were assessed. A 1-day point prevalence study was carried out
      using a protocol advocated by the European PU Advisory Panel. Patients' age,
      gender, severity of PU (grades I-IV), anatomical location of PU, and use of
      preventive measures were recorded. The Swedish language version of the Modified
      Norton Scale was used for PU risk assessment. Data were collected by nurses
      trained according to the Web-based training: PU classification, "ePuclas2." After
      21 months, a retrospective audit of the electronic records for patients
      identified with pressure ulcers was completed. The point prevalence of pressure
      ulcers was 23%. The total number of ulcers was 85, most were grade 1 (n = 39).
      The most common locations were the sacrum (n = 15) and the heel (n = 10). Three
      percent of patients (n = 9) had been assessed during their current hospital stay
      using a risk assessment tool. There was a statistically significant relationship
      between pressure ulcer occurrence and a low total score on the Modified Norton
      Scale. The patients' ages correlated significantly to the presence of a pressure
      ulcer. Patients with a pressure ulcer had a 3.6-fold increased risk of dying
      within 21 months, as compared with those without a pressure ulcer. Based on
      results from this quality improvement project, we recommend routine pressure
      ulcer risk assessment for all patients managed in a hospital setting such as
      ours. We further recommend that particular attention should be given to older and
      frail patients who are at higher risk for pressure ulcer occurrence and
      mortality. 

PMID- 24448616
TI  - Awareness and practice of wound disinfection among wound care nurses in Korea.
AB  - PURPOSE: The aim of this study was to assess the awareness and practice of wound
      disinfection among Korean wound care nurses. SUBJECTS AND SETTING: The target
      sample comprised 100 members of the Korea Wound Ostomy Continence Nurse
      Association. Seventy-eight wound care nurses responded to the questionnaire,
      yielding a response rate of 78%. METHODS: Potential respondents were contacted
      via e-mail and asked to complete a questionnaire designed for this study.
      RESULTS: Pressure ulcers were the most common wound type managed by WOC nurses,
      followed by surgical wounds. The mean score of items measuring awareness of wound
      disinfection practice and reported wound disinfection practice were 3.38 on a
      scale of 0 to 4 scale, and 3.14 on a scale of 0 to 4, respectively. Scores among
      items that queried awareness and practice in various methods for disinfecting a
      chronic wound disinfection were highest (3.74 and 3.67 out of 4, respectively)
      and scores of items querying disinfection with sodium hypochlorite were lowest
      (2.80 and 2.05 out of 4, respectively). There were significant differences
      between all items of awareness and reported practice except for disinfection with
      alcohol. Awareness of wound disinfection significantly correlated with reported
      practice. CONCLUSIONS: Developing an effective educational program to enhance
      awareness is necessary to improve practice of wound disinfection.

PMID- 24448617
TI  - Novel techniques using negative pressure wound therapy for the management of
      wounds with enterocutaneous fistulas in a long-term acute care facility.
AB  - Patient status and wound condition are important factors to consider when
      developing an appropriate wound management plan. Comorbid conditions such as
      diabetes mellitus, obesity, and peripheral vascular disease affect wound healing,
      as do complications, such as fistulas and infections. This article describes 3
      novel techniques, using negative pressure wound therapy with reticulated open
      cell foam for managing patients with wounds containing an enterocutaneous
      fistula. 

PMID- 24448618
TI  - Preoperative stoma site marking in the general surgery population.
AB  - PURPOSE: Preoperative teaching and stoma site marking are supported by research
      and professional organizations as interventions that can reduce the incidence of
      problematic stomas and improve patient outcomes. This study investigated the
      translation of this research into practice in the acute care surgery population.
      SUBJECTS AND SETTING: A retrospective chart review using convenience sampling was
      conducted at a large urban hospital in the Midwestern United States. METHODS:
      Thirty patients underwent a surgical procedure that resulted in the creation of a
      fecal ostomy over a 5-month period. Descriptive statistical analysis examined the
      reason for surgery, preoperative length of stay (LOS), the percentage of patients
      who received preoperative teaching and stoma marking and the relationship between
      preoperative LOS and the use of preoperative teaching and stoma marking. RESULTS:
      Twenty-one of 30 patients were admitted to hospital 24 hours or more before
      surgery. No participants were admitted urgently. Three (14%) of those admitted
      for more than 24 hours received preoperative marking or teaching. There was no
      significant relationship between preoperative LOS and preoperative teaching and
      stoma marking. CONCLUSIONS: The opportunity exists to promote successful
      adaptation in this surgical population through the implementation of the evidence
      based interventions of preoperative teaching and stoma marking. Additional study
      is needed to determine barriers to their use as well as to develop effective
      implementation strategies.

PMID- 24448619
TI  - Use of convexity in pouching: a comprehensive review.
AB  - A comprehensive literature review was conducted to examine research, current best
      evidence, and best practice recommendations associated with the use of convex
      skin barriers for patients living with an ostomy. The review revealed a
      fragmented array of citations related to convexity and a paucity of evidence
      regarding convexity product descriptions and application. Most convexity choices
      appear to be based on the clinician experience over time using trial and error to
      determine clinical application. Current descriptors used for convexity products
      are creating confusion, and a standardized approach to product nomenclature does
      not exist. The development of assistive clinical practice guidelines, in
      conjunction with further research, is recommended. 

PMID- 24448620
TI  - Health literacy needs related to incontinence and skin damage among family and
      friend caregivers of individuals with dementia.
AB  - PURPOSE: The purpose of this study was to describe health literacy needs related
      to incontinence and skin care among family or friend caregivers of individuals
      with Alzheimer disease (AD) and develop supportive and educational materials that
      address these needs. DESIGN: Descriptive. SUBJECTS AND SETTINGS: The sample
      included 48 family/friend adult caregivers of individuals who had advanced
      dementia. Caregivers were spouses (44%), daughters (31%), or extended family
      members/friends (25%) recruited from community-based agencies, with a mean age of
      64 +/- 14 years (mean +/- SD), and 75% were female. Nearly half (48%) had a
      racially or ethnically diverse background. METHODS: Focus groups, interviews, and
      written surveys were conducted to assess health literacy needs of AD caregivers
      related to incontinence and skin care; verbal responses were audiotaped,
      transcribed, and summarized. To address these needs, a set of educational and
      supportive materials was developed, whose content was directed by caregiver
      responses and supported by a literature review of current evidence and
      consultation with clinical and research experts. Study procedures were guided by
      an advisory committee of AD caregivers. RESULTS: Caregivers had numerous health
      literacy needs related to incontinence and skin care; areas of need were
      categorized into knowledge, skills, and attitudes. Caregivers expressed a need to
      validate the health literacy they possessed. Fourteen educational and supportive
      documents were developed to address these needs. CONCLUSION: Materials developed
      in this study are suitable to incorporate into interventions that support
      caregivers of persons with AD. They offer the potential to raise health literacy
      and care capacity of caregivers, increase communication with health care
      providers, and improve health outcomes of care recipients.

PMID- 24448621
TI  - Women's management of urinary incontinence in daily living.
AB  - PURPOSE: We investigated strategies used by older and working-aged women to
      manage urinary incontinence (UI) in their daily lives. DESIGN: Cross-sectional,
      descriptive study. SUBJECTS AND SETTING: The sample comprised 103 older (>65
      years; mean = 74.6 years) and 104 working-aged (18-65 years; mean = 50.3 years)
      community-dwelling Australian women with self-reported UI. They had experienced
      UI for an average of 5 years and a majority rated their UI severity as moderate
      to severe. INSTRUMENT: Based on a comprehensive literature review, a 93-item
      author-developed questionnaire was developed and pilot tested to identify the
      type and frequency of strategies used by participants to manage UI. Items were
      developed that queried demographic and lower urinary symptom characteristics
      (type, severity, duration). METHODS: Participants were recruited via public and
      privately funded continence clinics and an advertisement in a local newspaper,
      with a 66% retention rate following recruitment. Questionnaires were posted to
      participants with a reply paid envelope for return. RESULTS: The women used a
      range of strategies to manage UI in their daily lives. A large proportion of
      women from both groups chose to (1) go to the toilet immediately after urge
      (older 94%; working-aged 92%); (2) integrate urine loss management a normal part
      of everyday life (older 81%; working-aged 78%); (3) stopping activities that make
      them leak (older 85%; working-aged 83%); and (4) using pads and aids for urinary
      containment (older 87%; working-aged 73%). Older women were more likely to use
      most of the strategies identified in the questionnaire. These strategies included
      the following: stop drinking in the evening (older 64%; working-aged 43%; P =
      .003); organize their bedroom close to the toilet (older 61%; working-aged 36%; P
      = .001); limit travel (older 45%; working-aged 18%; P = < .001); limit
      socializing (older 30%; working-aged 11%; P = .001); and limit new relationships
      (older 25%; working-aged 11%; P = .01). Respondents engaged in a variety of
      hygiene measures such as washing (older 86%; working-aged 60%; P <= .001),
      changing pads frequently (older 76%; working-aged 58%; P = .008), and using
      deodorisers (older 68%; working-aged 50%; P <= .008). Working-aged women were
      more likely to modify (older 17%; working-aged 70%; P < .001) or avoid (older 8%;
      working-aged 32%; P = .001) sexual activity. CONCLUSION: Both older and younger
      women aimed to normalize UI in their daily lives, using strategies designed to
      keep the bladder empty, maintain secrecy, and preserve social continence.
      Knowledge of these strategies and the difference between older and working-aged
      women will enable health care professionals to initiate more targeted support and
      advice for women with UI.

PMID- 24448622
TI  - Overcoming WOCNCB test anxiety.

PMID- 24448623
TI  - Repair of a vesicocutaneous fistula using negative-pressure wound therapy and
      urinary diversion via a nephrostomy tube.
AB  - BACKGROUND: This article describes an unusual case of a vesicocutaneous fistula
      in a patient with a history of radiation therapy and recent abdominal surgery.
      CASE: A 61-year-old woman was transferred to our acute care facility from a
      rehabilitation facility, with poor nutritional intake and a concern for urine
      draining from her wound. A nephrostomy tube was placed (she had only 1
      functioning kidney) and negative-pressure wound therapy was used to close the
      fistula. CONCLUSION: Urinary diversion via a nephrostomy tube and negative
      pressure wound therapy were used to successfully and safely close this
      vesicocutaneous fistula.

PMID- 24448626
TI  - Which patients improve the most after arthritis rehabilitation? A study of
      predictors in patients with inflammatory arthritis in Northern Europe, the STAR
      ETIC collaboration.
AB  - OBJECTIVE: To study health-related quality of life (HRQoL) in arthritis
      rehabilitation performed by multidisciplinary teams in patients with chronic
      inflammatory arthritis. Predictors of change in health-related quality of life
      and the proportion of patients with clinical improvement were investigated.
      DESIGN: Multicentre prospective observational study in 4 European countries.
      METHODS: HRQoL was measured with the European Quality 5 Dimensions (EQ-5D) and
      the Short Form 36 Health Survey (SF-36) in 731 patients who underwent
      multidisciplinary rehabilitation. Potential predictors were physical functioning
      (Health Assessment Questionnaire (HAQ)), self-efficacy (Arthritis Self Efficacy
      Scale (ASES)), psychological health (Hopkins Symptom Check List (HSCL-25)),
      pain/fatigue (numeric rating scales (NRS)), age, sex, diagnosis, comorbidity,
      education, clinical setting and change of medication during rehabilitation.
      Analysis of covariance (ANCOVA) was used to assess for potential predictors and
      interactions. The minimal important differences for HRQoL were analysed. RESULTS:
      Reporting worse function (b 0.05, p = 0.01), less psychological well-being (b
      0.09, p = 0.000), and experiencing more pain (b 0.03, p = 0.000) or fatigue (b
      0.02, p = 0.000) at admission predicted improved HRQoL. Change in medication
      during rehabilitation (b 0.08, p = 0.013) was associated with greater improvement
      in HRQoL. These EQ-5D findings were supported by SF-36 findings. Positive minimal
      important differences were noted in 46% (EQ-5D) and 23-47% (SF-36 subscales) of
      the patients. CONCLUSION: Patients with more severe symptoms experienced the
      largest gain in HRQoL post-intervention. The results of this study are of value
      for selecting the right patients for rheumatological team rehabilitation.

PMID- 24448627
TI  - Oleamycins A and B: new antibacterial cyclic hexadepsipeptides isolated from a
      terrestrial Streptomyces sp.

PMID- 24448628
TI  - Structure and biological properties of lentztrehalose: a novel trehalose analog.
AB  - A new trehalose analog, lentztrehalose [4-O-(2,3-dihydroxy-3
      methylbutyl)trehalose], was isolated from an actinomycete Lentzea sp.
      Lentztrehalose is only weakly hydrolyzed by the trehalose-hydrolyzing enzyme,
      trehalase, so can be regarded as an enzyme-stable analog of trehalose. Although
      lentztrehalose does not show apparent toxicity to mammalian cells and microbes,
      it has antitumor activity in mice bearing S-180 sarcoma and Ehrlich carcinoma
      cells. In ovariectomized mice, lentztrehalose displayed a bone reinforcement
      effect in the femur that was superior to trehalose and induced non-morbid
      suppression of weight gain comparable with trehalose. These results indicate that
      enzyme-stable analogs of trehalose, such as lentztrehalose, may be more
      beneficial for human health and thus have potential as substitutes for trehalose
      as a sweetener. 

PMID- 24448629
TI  - High-mobility Bi2Se3 nanoplates manifesting quantum oscillations of surface
      states in the sidewalls.
AB  - Magnetotransport measurements of topological insulators are very important to
      reveal the exotic topological surface states for spintronic applications.
      However, the novel properties related to the surface Dirac fermions are usually
      accompanied by a large linear magnetoresistance under perpendicular magnetic
      field, which makes the identification of the surface states obscure. Here, we
      report prominent Shubnikov-de Haas (SdH) oscillations under an in-plane magnetic
      field, which are identified to originate from the surface states in the sidewalls
      of topological insulator Bi2Se3 nanoplates. Importantly, the SdH oscillations
      appear with a dramatically weakened magnetoresistance background, offering an
      easy path to probe the surface states directly when the coexistence of surface
      states and bulk conduction is inevitable. Moreover, under a perpendicular
      magnetic field, the oscillations in Hall conductivity have peak-to-valley
      amplitudes of 2 e(2)/h, giving confidence to achieve a quantum Hall effect in
      this system. A cross-section view of the nanoplate shows that the sidewall is
      (015) facet dominant and therefore forms a 58 degrees  angle with regard to the
      top/bottom surface instead of being perpendicular; this gives credit to the
      surface states' behavior as two-dimensional transport.

PMID- 24448631
TI  - Improving the performance of protein kinase identification via high dimensional
      protein-protein interactions and substrate structure data.
AB  - As a crucial post-translational modification, protein phosphorylation regulates
      almost all basic cellular processes. Recently, thousands of phosphorylation sites
      have been discovered by large-scale phospho-proteomics studies, but only about
      20% of them have information regarding catalytic kinases, which brings a great
      challenge for correct identification of the protein kinases responsible for
      experimentally verified phosphorylation sites. In most existing identification
      tools, only a local sequence was selected to construct predictive models, and
      information regarding protein-protein interaction (PPI) was adopted for further
      filtering. However, the limited information utilized by these tools is not
      sufficient to identify protein kinases responsible for phosphorylated proteins.
      In this work, a novel computational approach that fully incorporates PPI and
      substrate structure information is proposed to improve the performance of human
      protein kinase identification. To handle the issue of high-dimensional PPI and
      structure data, a two-step feature selection algorithm that incorporates a
      support vector machine (SVM), is designed to detect information useful in
      discriminating the corresponding kinase of phosphorylation sites. Benchmark
      datasets for kinase identification are constructed using human protein
      phosphorylation data extracted from the latest Phospho.ELM database. With the
      selected PPI and structure features, the performance of kinase identification is
      significantly enhanced as compared with that obtained by using only sequence
      information. To further verify our method, we compared it with the state-of-the
      art tools NetworKIN and IGPS at two stringency levels with medium (>90.0%) and
      high (>99.0%) specificity. The results show that our method outperforms existing
      tools in identifying protein kinases. Further evaluation demonstrates that our
      method also has superior performance on different hierarchical levels including
      kinase, subfamily, family and group. 

PMID- 24448630
TI  - The impact of first episode psychosis on sibling quality of life.
AB  - PURPOSE: The adverse impact of first episode psychosis (FEP) upon parents'
      quality of life (QoL) has been well documented. However, the determinants and
      levels of QoL remain poorly understood in siblings of young people experiencing
      FEP. This study aimed to characterise and establish the predictors of QoL for
      siblings of young people with FEP. METHOD: Survey methodology was used to examine
      the experience of 157 siblings in the first 18 months of their brother or
      sister's treatment for FEP. The World Health Organisation Quality of Life Scale
      Bref (WHOQOL-Bref) was used to assess siblings' QoL. A series of multivariate
      regression analyses were conducted to determine the relationships between illness
      characteristics and siblings' QoL. RESULTS: Younger sisters reported the lowest
      satisfaction of QoL. Older brothers were the most satisfied. When the young
      person with FEP had attempted suicide and/or had been physically violent,
      siblings reported less satisfaction in all domains of QoL. Living with the ill
      brother or sister resulted in less satisfaction in the social domain.
      Multivariate analysis showed that female gender was a significant factor in
      explaining the impact of illness-related variables on QoL, particularly suicide
      attempts. CONCLUSION: Suicide attempts and a history of violence impacted
      negatively on all four domains of QoL. Female siblings are at higher risk of
      reduced QoL and may be particularly vulnerable to the effects of suicide attempts
      and violence. These findings have significant implications for early, targeted
      interventions for this vulnerable group.

PMID- 24448632
TI  - Estimating cyanobacteria community dynamics and its relationship with
      environmental factors.
AB  - The cyanobacteria community dynamics in two eutrophic freshwater bodies (Tiegang
      Reservoir and Shiyan Reservoir) was studied with both a traditional microscopic
      counting method and a PCR-DGGE genotyping method. Results showed that
      cyanobacterium Phormidium tenue was the predominant species; twenty-six
      cyanobacteria species were identified in water samples collected from the two
      reservoirs, among which fourteen were identified with the morphological method
      and sixteen with the PCR-DGGE method. The cyanobacteria community composition
      analysis showed a seasonal fluctuation from July to December. The cyanobacteria
      population peaked in August in both reservoirs, with cell abundances of 3.78 *
      10(8) cells L(-1) and 1.92 * 10(8) cells L(-1) in the Tiegang and Shiyan
      reservoirs, respectively. Canonical Correspondence Analysis (CCA) was applied to
      further investigate the correlation between cyanobacteria community dynamics and
      environmental factors. The result indicated that the cyanobacteria community
      dynamics was mostly correlated with pH, temperature and total nitrogen. This
      study demonstrated that data obtained from PCR-DGGE combined with a traditional
      morphological method could reflect cyanobacteria community dynamics and its
      correlation with environmental factors in eutrophic freshwater bodies.

PMID- 24448633
TI  - Psychosocial work environment, stress factors and individual characteristics
      among nursing staff in psychiatric in-patient care.
AB  - The psychosocial work environment is an important factor in psychiatric in
      patient care, and knowing more of its correlates might open up new paths for
      future workplace interventions. Thus, the aims of the present study were to
      investigate perceptions of the psychosocial work environment among nursing staff
      in psychiatric in-patient care and how individual characteristics--Mastery, Moral
      Sensitivity, Perceived Stress, and Stress of Conscience--are related to different
      aspects of the psychosocial work environment. A total of 93 nursing staff members
      filled out five questionnaires: the QPSNordic 34+, Perceived Stress Scale, Stress
      of Conscience Questionnaire, Moral Sensitivity Questionnaire, and Mastery scale.
      Multivariate analysis showed that Perceived Stress was important for
      Organisational Climate perceptions. The Stress of Conscience subscale Internal
      Demands and Experience in current units were indicators of Role Clarity. The
      other Stress of Conscience subscale, External Demands and Restrictions, was
      related to Control at Work. Two types of stress, Perceived Stress and Stress of
      Conscience, were particularly important for the nursing staff's perception of the
      psychosocial work environment. Efforts to prevent stress may also contribute to
      improvements in the psychosocial work environment.

PMID- 24448634
TI  - Connectedness to nature and public (skin) health perspectives: results of a
      representative, population-based survey among Austrian residents.
AB  - Connectedness to nature (CN) influences motivation to have contact with outdoor
      natural environments. Spending leisure time in natural environments is beneficial
      for human health and well-being. Besides these positive effects, health risks of
      open-air activities are mainly related to unprotected sun light exposure
      associated acute and chronic skin hazards. Thus, we conducted a cross-sectional,
      representative telephone survey among Austrian residents to study the association
      of perceived CN level with sun-exposure knowledge, tanning habits, and sun
      protective behaviour. In total, 1,500 study subjects (50.5% females) participated
      in this questionnaire survey. Although knowledge about tanning and motives to tan
      were similar among genders, females performed more photoprotective measures and
      were more connected to nature (all p < 0.001) compared to males. Older age and
      outdoor sport were significant gender-independent predictor variables influencing
      perceived CN level. Additionally, level of education was relevant in male CN,
      whereas non-smoking and higher knowledge were predictive of female CN. This
      survey provides so far unreported empirical data on the relationship between
      nature connectedness and skin health-relevant recreational habits of Austrian
      residents. The findings suggest to integrate hitherto neglected gender-specific
      Public (Skin) Health promotion when counselling on the manifold health advantages
      of outdoor activities. 

PMID- 24448635
TI  - Genetically engineered bacteriophage delivers a tumor necrosis factor alpha
      antagonist coating on neural electrodes.
AB  - This paper reports a novel approach for the formation of anti-inflammatory
      surface coating on a neural electrode. The surface coating is realized using a
      recombinant f88 filamentous bacteriophage, which displays a short platinum
      binding motif and a tumor necrosis factor alpha antagonist (TNF-alpha antagonist)
      on p3 and p8 proteins, respectively. The recombinant bacteriophages are
      immobilized on the platinum surface by a simple dip coating process. The
      selective and stable immobilization of bacteriophages on a platinum electrode is
      confirmed by quartz crystal microbalance with dissipation monitoring, atomic
      force microscope and fluorescence microscope. From the in vitro cell viability
      test, the inflammatory cytokine (TNF-alpha) induced cell death was prevented by
      presenting recombinant bacteriophage coating, albeit with no significant
      cytotoxic effect. It is also observed that the bacteriophage coating does not
      have critical effects on the electrochemical properties such as impedance and
      charge storage capacities. Thus, this approach demonstrates a promising anti
      apoptotic as well as anti-inflammatory surface coating for neural implant
      applications. 

PMID- 24448636
TI  - Self-weaving CNT-LiNbO(3) nanoplate-polypyrrole hybrid as a flexible anode for Li
      ion batteries.
AB  - LiNbO3 nanoplates were directly grown on a self-weaving CNT-network, which was
      then decorated with polypyrrole to form a flexible electrode. This novel nano
      structured anode exhibits superior performance, i.e., high rate discharge
      capacity and excellent cycle performance. 

PMID- 24448637
TI  - shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer
      cells.
AB  - PURPOSE: Breast cancer is the cause for highest number of cancer-related death
      among women worldwide. This study was focused on investigating the role of zinc
      finger protein X-linked (ZFX) in human breast cancer. METHODS: Expression levels
      of ZFX were analyzed in 99 patients and four breast cancer cell lines. Lentivirus
      mediated RNA interference was applied to silence ZFX expression, and the effects
      of ZFX knockdown on the growth of breast cancer cells were investigated. RESULTS:
      The immunohistochemical expression of ZFX was higher in more advanced tumor
      tissues. ZFX was also overexpressed in multiple breast cancer cell lines.
      Knockdown of ZFX inhibited cell proliferation and colony formation of MCF-7 and
      MDA-MB-231 cells. Moreover, ZFX silencing resulted in cell cycle arrest at G0/G1
      phase. Depletion of ZFX decreased the phosphorylation level of AKT and increased
      the phosphorylation level of ERK2 and the expression of cyclin D1, which is
      involved in cell survival and cell cycle regulation. CONCLUSIONS: These findings
      suggest that ZFX plays an important role in breast cancer development and could
      be a potential therapeutic target for breast cancer.

PMID- 24448638
TI  - Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in
      combination with gemcitabine in US patients with advanced solid tumors.
AB  - PURPOSE: AZD7762 is a Chk1 kinase inhibitor which increases sensitivity to DNA
      damaging agents, including gemcitabine. We evaluated the safety of AZD7762
      monotherapy and with gemcitabine in advanced solid tumor patients. EXPERIMENTAL
      DESIGN: In this Phase I study, patients received intravenous AZD7762 on days 1
      and 8 of a 14-day run-in cycle (cycle 0; AZD7762 monotherapy), followed by
      AZD7762 plus gemcitabine 750-1,000 mg/m(2) on days 1 and 8, every 21 days, in
      ascending AZD7762 doses (cycle 1; combination therapy). RESULTS: Forty-two
      patients received AZD7762 6 mg (n = 9), 9 mg (n = 3), 14 mg (n = 6), 21 mg (n =
      3), 30 mg (n = 7), 32 mg (n = 6), and 40 mg (n = 8), in combination with
      gemcitabine. Common adverse events (AEs) were fatigue [41 % (17/42) patients],
      neutropenia/leukopenia [36 % (15/42) patients], anemia/Hb decrease [29 % (12/42)
      patients] and nausea, pyrexia and alanine aminotransferase/aspartate
      aminotransferase increase [26 % (11/42) patients each]. Grade >=3 AEs occurred in
      19 and 52 % of patients in cycles 0 and 1, respectively. Cardiac dose-limiting
      toxicities occurred in two patients (both AZD7762 monotherapy): grade 3 troponin
      I increase (32 mg) and grade 3 myocardial ischemia with chest pain,
      electrocardiogram changes, decreased left ventricular ejection fraction, and
      increased troponin I (40 mg). AZD7762 exposure increased linearly. Gemcitabine
      did not affect AZD7762 pharmacokinetics. Two non-small-cell lung cancer patients
      achieved partial tumor responses (AZD7762 6 mg/gemcitabine 750 mg/m(2) and
      AZD7762 9 mg cohort). CONCLUSIONS: The maximum-tolerated dose of AZD7762 in
      combination with gemcitabine 1,000 mg/m(2) was 30 mg. Although development of
      AZD7762 is not going forward owing to unpredictable cardiac toxicity, Chk1
      remains an important therapeutic target.

PMID- 24448639
TI  - UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system
      review and meta-analysis in Asians.
AB  - PURPOSE: Previous studies confirmed that genotyping uridine diphosphate
      glucuronosyltransferase (UGT) 1A1*28 polymorphisms could predict the side effects
      in cancer patients using irinotecan (IRI) and then reduce IRI-induced toxicity by
      preventative treatment or decrease in dose. However, the association between
      UGT1A1*6 polymorphisms and IRI-induced severe toxicity in Asian patients is still
      unclear. The aim of this study was to evaluate the association between UGT1A1*6
      polymorphisms and IRI-induced severe neutropenia as well as diarrhea in Asian
      patients. METHODS: We searched all papers on PubMed and Embase from February 1998
      to August 2013. Then we assessed the methodologies quality, extracted data and
      made statistics analysis using STATA software. To uncover the sources of
      heterogeneity, subgroup meta-analysis was conducted according to the dosage of
      IRI. RESULTS: Eleven papers were included according to the inclusion and
      exclusion criteria after searching Pubmed and Embase. Overall, an increased risk
      of severe toxicity in Asian patients with UGT1A1*6 polymorphisms was found.
      Patients with heterozygous variant of UGT1A1*6 showed an increased risk [odds
      ratio (OR) = 1.98, 95 % confidence intervals (CI) 1.45-2.71, P < 0.001], and
      homozygous mutation showed an even higher risk (OR = 4.44, 95 % CI 2.42-8.14, P <
      0.001) for severe neutropenia. For severe diarrhea, heterozygous variant of
      UGT1A1*6 showed no significant risk, while the homozygous variant performed a
      notable risk (OR = 3.51, 95 % CI 1.41-8.73, P = 0.007). Subgroup meta-analysis
      indicated that for patients harboring either heterozygous or homozygous variant,
      low dose of IRI also presented comparably increased risk in suffering severe
      neutropenia. CONCLUSION: In this meta-analysis, UGT1A1*6 polymorphisms were
      revealed as potential biomarkers, predicting IRI-induced severe toxicity in
      patients from Asia, and increased incidences of severe neutropenia could occur in
      both high/medium and low doses of IRI.

PMID- 24448640
TI  - Phase I dosage finding and pharmacokinetic study of intravenous topotecan and
      oral erlotinib in adults with refractory solid tumors.
AB  - PURPOSE: Topotecan is widely used for refractory solid tumors but multi-drug
      resistance may occur due to tumor expression of ATP-binding cassette (ABC)
      transporters. Since erlotinib, an inhibitor of the epidermal growth factor
      receptor, also inhibits several ABC transporters, we performed a phase I study to
      evaluate the safety, efficacy, and pharmacokinetics of intravenous topotecan
      given in combination with erlotinib. METHODS: Patients received 150 mg of oral
      erlotinib daily and a 30 min intravenous infusion of topotecan on days 1-5 of a
      21-day cycle. Dosage escalation of topotecan occurred with a starting dosage of
      0.75 mg/m(2). The pharmacokinetics of topotecan was evaluated on day 1 of cycle 1
      without erlotinib and on day 1 of cycle 2 or 3 with erlotinib. RESULTS: Twenty
      nine patients were enrolled. The maximum tolerated dosage was determined to be
      1.0 mg/m(2). Dose-limiting toxicities included neutropenia and thrombocytopenia.
      The average duration of treatment was 97 days. Two partial responses were
      observed. Topotecan clearance and exposure were similar with and without
      erlotinib. CONCLUSIONS: The combination of topotecan and erlotinib is tolerable
      at clinically effective doses. Erlotinib does not affect the disposition of
      topotecan to a clinically significant extent.

PMID- 24448641
TI  - Where there's smoke . . .

PMID- 24448642
TI  - Direct estimates of natural selection in Iberia indicate calcium absorption was
      not the only driver of lactase persistence in Europe.
AB  - Lactase persistence (LP) is a genetically determined trait whereby the enzyme
      lactase is expressed throughout adult life. Lactase is necessary for the
      digestion of lactose--the main carbohydrate in milk--and its production is
      downregulated after the weaning period in most humans and all other mammals
      studied. Several sources of evidence indicate that LP has evolved independently,
      in different parts of the world over the last 10,000 years, and has been subject
      to strong natural selection in dairying populations. In Europeans, LP is strongly
      associated with, and probably caused by, a single C to T mutation 13,910 bp
      upstream of the lactase (LCT) gene (-13,910*T). Despite a considerable body of
      research, the reasons why LP should provide such a strong selective advantage
      remain poorly understood. In this study, we examine one of the most widely cited
      hypotheses for selection on LP--that fresh milk consumption supplemented the poor
      vitamin D and calcium status of northern Europe's early farmers (the calcium
      assimilation hypothesis). We do this by testing for natural selection on 
      13,910*T using ancient DNA data from the skeletal remains of eight late Neolithic
      Iberian individuals, whom we would not expect to have poor vitamin D and calcium
      status because of relatively high incident UVB light levels. None of the eight
      samples successfully typed in the study had the derived T-allele. In addition, we
      reanalyze published data from French Neolithic remains to both test for
      population continuity and further examine the evolution of LP in the region.
      Using simulations that accommodate genetic drift, natural selection, uncertainty
      in calibrated radiocarbon dates, and sampling error, we find that natural
      selection is still required to explain the observed increase in allele frequency.
      We conclude that the calcium assimilation hypothesis is insufficient to explain
      the spread of LP in Europe.

PMID- 24448643
TI  - Natural variation of heterokaryon incompatibility gene het-c in Podospora
      anserina reveals diversifying selection.
AB  - In filamentous fungi, allorecognition takes the form of heterokaryon
      incompatibility, a cell death reaction triggered when genetically distinct hyphae
      fuse. Heterokaryon incompatibility is controlled by specific loci termed het
      loci. In this article, we analyzed the natural variation in one such fungal
      allorecognition determinant, the het-c heterokaryon incompatibility locus of the
      filamentous ascomycete Podospora anserina. The het-c locus determines an
      allogenic incompatibility reaction together with two unlinked loci termed het-d
      and het-e. Each het-c allele is incompatible with a specific subset of the het-d
      and het-e alleles. We analyzed variability at the het-c locus in a population of
      110 individuals, and in additional isolates from various localities. We
      identified a total of 11 het-c alleles, which define 7 distinct incompatibility
      specificity classes in combination with the known het-d and het-e alleles. We
      found that the het-c allorecognition gene of P. anserina is under diversifying
      selection. We find a highly unequal allele distribution of het-c in the
      population, which contrasts with the more balanced distribution of functional
      groups of het-c based on their allorecognition function. One explanation for the
      observed het-c diversity in the population is its function in allorecognition.
      However, alleles that are most efficient in allorecognition are rare. An
      alternative and not exclusive explanation for the observed diversity is that het
      c is involved in pathogen recognition. In Arabidopsis thaliana, a homolog of het
      c is a pathogen effector target, supporting this hypothesis. We hypothesize that
      the het-c diversity in P. anserina results from both its functions in pathogen
      defense, and allorecognition. 

PMID- 24448644
TI  - Effects of MDMA and Intranasal oxytocin on social and emotional processing.
AB  - MDMA (+/- 3,4-methylenedioxymethamphetamine, 'ecstasy') is used recreationally,
      reportedly because it increases feelings of empathy, sociability, and
      interpersonal closeness. One line of evidence suggests that MDMA produces these
      effects by releasing oxytocin, a peptide involved in social bonding. In the
      current study, we investigated the acute effects of MDMA and oxytocin on social
      and emotional processing in healthy human volunteers. MDMA users (N = 65)
      participated in a 4-session, within-between-subjects study in which they received
      oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under
      double-blind conditions. The primary outcomes included measures of emotion
      recognition and sociability (desire to be with others). Cardiovascular and
      subjective effects were also assessed. As expected, MDMA dose-dependently
      increased heart rate and blood pressure and feelings of euphoria (eg, 'High' and
      'Like Drug'). On measures of social function, MDMA impaired recognition of angry
      and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire
      to be with others, compared with placebo. Oxytocin produced small but significant
      increases in feelings of sociability and enhanced recognition of sad facial
      expressions. Additionally, responses to oxytocin were related to responses to
      MDMA with subjects on two subjective measures of sociability. Thus, MDMA
      increased euphoria and feelings of sociability, perhaps by reducing sensitivity
      to subtle signs of negative emotions in others. The present findings provide only
      limited support for the idea that oxytocin produces the prosocial effects of
      MDMA.

PMID- 24448646
TI  - Control of the anisotropic shape of cobalt nanorods in the liquid phase: from
      experiment to theory... and back.
AB  - The polyol process is one of the few methods allowing the preparation of metal
      nanoparticles in solution. Hexagonal close packed monocrystalline Co nanorods are
      easily obtained in basic 1,2-butanediol at 448 K after a few minutes using a
      Co(II) dicarboxylate precursor. By using a combined experimental and theoretical
      approach, this study aims at a better understanding of the growth of anisotropic
      cobalt ferromagnetic nanoparticles by the polyol process. The growth of Co
      nanorods along the c axis of the hexagonal system was clearly evidenced by
      transmission electron microscopy, while the mean diameter was found to be almost
      constant at about 15 nm. Powder X-ray diffraction data showed that metallic
      cobalt was generated at the expense of a non-reduced solid lamellar intermediate
      phase which can be considered as a carboxylate ligand reservoir. Density
      functional theory calculations combined with a thermodynamic approach
      unambiguously showed that the main parameter governing the shape of the objects
      is the chemical potential of the carboxylate ligand: the crystal habit was deeply
      modified from rods to platelets when increasing the concentration of the ligand,
      i.e. its chemical potential. The approach presented in this study could be
      extended to a large number of particle types and growth conditions, where ligands
      play a key role in determining the particle shape.

PMID- 24448645
TI  - Long-term memory deficits are associated with elevated synaptic ERK1/2 activation
      and reversed by mGluR5 antagonism in an animal model of autism.
AB  - A significant proportion of patients with autism exhibit some degree of
      intellectual disability. The BTBR T(+) Itpr3(tf)/J mouse strain exhibits
      behaviors that align with the major diagnostic criteria of autism. To further
      evaluate the BTBR strain's cognitive impairments, we quantified hippocampus
      dependent object location memory (OLM) and found that one-third of the BTBR mice
      exhibited robust memory, whereas the remainder did not. Fluorescence
      deconvolution tomography was used to test whether synaptic levels of activated
      extracellular signal-regulated kinase 1/2 (ERK1/2), a protein that contributes
      importantly to plasticity, correlate with OLM scores in individual mice. In
      hippocampal field CA1, the BTBRs had fewer post-synaptic densities associated
      with high levels of phosphorylated (p-) ERK1/2 as compared with C57BL/6 mice.
      Although counts of p-ERK1/2 immunoreactive synapses did not correlate with OLM
      performance, the intensity of synaptic p-ERK1/2 immunolabeling was negatively
      correlated with OLM scores across BTBRs. Metabotropic glutamate receptor (mGluR)
      5 signaling activates ERK1/2. Therefore, we tested whether treatment with the
      mGluR5 antagonist MPEP normalizes synaptic and learning measures in BTBR mice:
      MPEP facilitated OLM and decreased synaptic p-ERK1/2 immunolabeling intensity
      without affecting numbers of p-ERK1/2+ synapses. In contrast, semi-chronic
      ampakine treatment, which facilitates memory in other models of cognitive
      impairment, had no effect on OLM in BTBRs. These results suggest that
      intellectual disabilities associated with different neurodevelopmental disorders
      on the autism spectrum require distinct therapeutic strategies based on
      underlying synaptic pathology. 

PMID- 24448647
TI  - The secreted protein ANGPTL2 promotes metastasis of osteosarcoma cells through
      integrin alpha5beta1, p38 MAPK, and matrix metalloproteinases.
AB  - The tumor microenvironment can enhance the invasive capacity of tumor cells. We
      showed that expression of angiopoietin-like protein 2 (ANGPTL2) in osteosarcoma
      (OS) cell lines increased and the methylation of its promoter decreased with time
      when grown as xenografts in mice compared with culture. Compared with cells grown
      in normal culture conditions, the expression of genes encoding DNA demethylation
      related enzymes increased in tumor cells implanted into mice or grown in hypoxic,
      serum-starved culture conditions. ANGPTL2 expression in OS cell lines correlated
      with increased tumor metastasis and decreased animal survival by promoting tumor
      cell intravasation mediated by the integrin alpha5beta1, p38 mitogen-activated
      protein kinase, and matrix metalloproteinases. The tolloid-like 1 (TLL1) protease
      cleaved ANGPTL2 into fragments in vitro that did not enhance tumor progression
      when overexpressed in xenografts. Expression of TLL1 was weak in OS patient
      tumors, suggesting that ANGPTL2 may not be efficiently cleaved upon secretion
      from OS cells. These findings demonstrate that preventing ANGPTL2 signaling
      stimulated by the tumor microenvironment could inhibit tumor cell migration and
      metastasis. 

PMID- 24448648
TI  - Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress
      responses.
AB  - Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5) mediates
      reactive oxygen species (ROS)-induced cell death. When activated by ROS, ASK1
      ultimately becomes ubiquitinated and degraded by the proteasome, a process that
      is antagonized by the ubiquitin-specific protease USP9X. Using a functional siRNA
      (small interfering RNA) screen in HeLa cells, we identified Roquin-2 (also called
      RC3H2) as an E3 ubiquitin ligase required for ROS-induced ubiquitination and
      degradation of ASK1. In cells treated with H2O2, knockdown of Roquin-2 promoted
      sustained activation of ASK1 and the downstream stress-responsive kinases JNK (c
      Jun amino-terminal kinase) and p38 MAPK (mitogen-activated protein kinase), and
      led to cell death. The nematode Caenorhabditis elegans produces ROS as a defense
      mechanism in response to bacterial infection. In C. elegans, mutation of the gene
      encoding the Roquin-2 ortholog RLE-1 promoted accumulation of the activated form
      of the ASK1 ortholog NSY-1 and conferred resistance to infection by the bacteria
      Pseudomonas aeruginosa. Thus, these data suggest that degradation of ASK1
      mediated by Roquin-2 is an evolutionarily conserved mechanism required for the
      appropriate regulation of stress responses, including pathogen resistance and
      cell death. 

PMID- 24448650
TI  - Low-volume high-intensity interval training vs continuous aerobic cycling in
      patients with chronic heart failure: a pragmatic randomised clinical trial of
      feasibility and effectiveness.
AB  - OBJECTIVES: The health benefits of high-intensity interval training in cardiac
      rehabilitation warrant further research. We compared the effectiveness of low
      volume high-intensity interval training vs continuous aerobic exercise training
      in chronic heart failure. DESIGN/SETTINGS: Unblinded, two arm parallel design
      with random assignment to exercise interventions in out-patient hospital
      rehabilitation gym. METHODS: Patients with signs of chronic heart failure and
      ejection fraction < 45%, (mean age: 59.1 years (standard deviation (SD) 8.6); 3
      women) completed 6 months of exercise using continuous aerobic exercise training
      (n = 9) or high-intensity interval training (n = 8). Cardiorespiratory fitness
      was determined during cycle ergometry using respiratory gas exchange analysis.
      Functional capacity was assessed via sit-to-stand and gait speed. Quality of life
      was assessed using the MOS Short-Form 36 and Minnesota living with heart failure
      questionnaires. Cardiac autonomic regulation was assessed using Heart Rate
      Variability. RESULTS: Analysis of Covariance revealed significant time effects
      but no group * time interactions for exercise and functional capacity outcomes.
      Peak oxygen uptake (VO2peak) improved by a mean of 14.9% (SD 16.3%) from baseline
      and by 22% (SD 28.3) at ventilatory threshold in both groups. Sit-to-stand (11.9
      (SD 11%)) and gait speed (16.0 (SD 19%)) improved similarly in both groups. No
      changes in quality of life or heart rate variability were noted. Training
      adaptations in high-intensity interval training were achieved despite a
      significantly reduced time commitment and total work volume compared to
      continuous aerobic exercise training. CONCLUSION: Low-volume high-intensity
      interval training is a feasible and well tolerated training modality in cardiac
      rehabilitation settings, but is not more effective than continuous aerobic
      exercise training.

PMID- 24448649
TI  - The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal
      biogenesis, and clearance of cellular debris.
AB  - The discovery of a gene network regulating lysosomal biogenesis and its
      transcriptional regulator transcription factor EB (TFEB) revealed that cells
      monitor lysosomal function and respond to degradation requirements and
      environmental cues. We report the identification of transcription factor E3
      (TFE3) as another regulator of lysosomal homeostasis that induced expression of
      genes encoding proteins involved in autophagy and lysosomal biogenesis in ARPE-19
      cells in response to starvation and lysosomal stress. We found that in nutrient
      replete cells, TFE3 was recruited to lysosomes through interaction with active
      Rag guanosine triphosphatases (GTPases) and exhibited mammalian (or mechanistic)
      target of rapamycin complex 1 (mTORC1)-dependent phosphorylation. Phosphorylated
      TFE3 was retained in the cytosol through its interaction with the cytosolic
      chaperone 14-3-3. After starvation, TFE3 rapidly translocated to the nucleus and
      bound to the CLEAR elements present in the promoter region of many lysosomal
      genes, thereby inducing lysosomal biogenesis. Depletion of endogenous TFE3
      entirely abolished the response of ARPE-19 cells to starvation, suggesting that
      TFE3 plays a critical role in nutrient sensing and regulation of energy
      metabolism. Furthermore, overexpression of TFE3 triggered lysosomal exocytosis
      and resulted in efficient cellular clearance in a cellular model of a lysosomal
      storage disorder, Pompe disease, thus identifying TFE3 as a potential therapeutic
      target for the treatment of lysosomal disorders. 

PMID- 24448651
TI  - Predicting DNA-binding sites of proteins based on sequential and 3D structural
      information.
AB  - Protein-DNA interactions play important roles in many biological processes. To
      understand the molecular mechanisms of protein-DNA interaction, it is necessary
      to identify the DNA-binding sites in DNA-binding proteins. In the last decade,
      computational approaches have been developed to predict protein-DNA-binding sites
      based solely on protein sequences. In this study, we developed a novel predictor
      based on support vector machine algorithm coupled with the maximum relevance
      minimum redundancy method followed by incremental feature selection. We
      incorporated not only features of physicochemical/biochemical properties,
      sequence conservation, residual disorder, secondary structure, solvent
      accessibility, but also five three-dimensional (3D) structural features
      calculated from PDB data to predict the protein-DNA interaction sites. Feature
      analysis showed that 3D structural features indeed contributed to the prediction
      of DNA-binding site and it was demonstrated that the prediction performance was
      better with 3D structural features than without them. It was also shown via
      analysis of features from each site that the features of DNA-binding site itself
      contribute the most to the prediction. Our prediction method may become a useful
      tool for identifying the DNA-binding sites and the feature analysis described in
      this paper may provide useful insights for in-depth investigations into the
      mechanisms of protein-DNA interaction. 

PMID- 24448654
TI  - The effects of silver, silicon-containing apatite towards bacteria and cell
      responses.
AB  - An integrated approach is proposed to incorporate silicon and silver into
      hydroxyapatite (HA) to enhance the biological response and reduce implant-related
      infection in bone substitutes. This study examined the responses of
      Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacteria to
      silver, silicon-containing apatite (Ag,Si-HA). Scanning electron microscopy
      images revealed significant reduction in adherence of S. aureus and E. coli
      bacteria on Ag,Si-HA as compared to HA. The antibacterial property of Ag,Si-HA
      was shown from a 7-log reduction of S. aureus population in the test solution and
      on the sample's surface as compared to HA at day 7. Rapid inhibition of the
      adherent bacteria suggested that the antibacterial action of Ag incorporated in
      Ag,Si-HA could be attributed to the Ag(+) ions on the crystal surface rather than
      the released Ag(+) ions. Presence of Ag may influence the biological response of
      HA and as such, the long-term interaction between human adipose-derived
      mesenchymal stem cells and Ag,Si-HA was evaluated in-vitro. An alamarBlueTM assay
      showed higher cell proliferation for Ag,Si-HA as compared to HA from day 3
      onwards. Immunofluorescence staining revealed well-spread actin cytoskeletons on
      Ag,Si-HA. In addition, signs of extracellular matrix secretion and
      biomineralization were observed on Ag,Si-HA at day 14 onwards. Results
      demonstrated enhanced bone differentiation on Ag,Si-HA, as indicated by a higher
      level of protein expressions (type 1 collagen and osteocalcin) from day 14 to 21.
      Therefore, the incorporation of Ag and Si complement each other by endowing HA
      with antibacterial property, and concurrently promoting biological performance of
      the cells.

PMID- 24448653
TI  - A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in
      fibrotic steatohepatitis in a dietary rat model.
AB  - BACKGROUND AND AIMS: Our previous study indicated that hepatic bile acids (BAs)
      may have deposited and stimulated the pathogenesis of a high fat-cholesterol
      (HFC) diet-induced fibrotic steatohepatitis in stroke-prone spontaneously
      hypertensive 5/Dmcr rats, based on dysregulated BA homeostasis pathways. We aimed
      to further characterize BA profiles in liver and evaluate their relationships to
      liver injury using this model. METHODS: Hepatic 21 BA levels were determined by
      ultra-performance liquid chromatography-tandem mass spectrometry, and their
      correlations with macrovesicular steatosis score, serum alanine aminotransferase
      (ALT) level and quantified fibrotic area were assessed using Spearman and Pearson
      correlations. RESULTS: Compared to control, BAs highly accumulated in HFC-fed rat
      liver at 2 weeks: cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic
      acid (CDCA) were major species, thereafter, levels of CA and DCA declined, but
      CDCA species persistently increased, which induced a decrease in total CA/total
      CDCA ratio at 8 and 14 weeks. CDCA species positively, while total CA/total CDCA
      negatively, correlated with macrovesicular steatosis score, serum ALT and
      quantified fibrotic area. Unlike control, total ursodeoxycholic acid was minor in
      HFC-fed rat liver, and inversely correlated to aforementioned indicators of liver
      injury; total glyco-BAs, rather than tauro-BAs, were predominant in HFC-fed rat
      liver, and positively correlated with macrovesicular steatosis score. Moreover,
      its ratio to total tauro-BAs positively correlated with each parameter of liver
      injury, while inverse associations were detected for total tauro-BAs.
      CONCLUSIONS: Hepatic BA accumulation may potentiate liver disease. CDCA and glyco
      BAs play a more important role in the pathogenesis of fibrotic steatohepatitis.

PMID- 24448655
TI  - Single-shot measurement of >1010 pulse contrast for ultra-high peak-power lasers.
AB  - Real-time pulse-contrast observation with a high dynamic range is a prerequisite
      to tackle the contrast challenge in ultra-high peak-power lasers. However, the
      commonly used delay-scanning cross-correlator (DSCC) can only provide the time
      consumed measurements for repetitive lasers. Single-shot cross-correlator (SSCC)
      becomes essential in optimizing laser systems and exploring contrast mechanisms.
      Here we report our progress in developing SSCC towards its practical use. By
      integrating both the techniques of scattering-noise reduction and sensitive
      parallel detection into SSCC, we demonstrate a high dynamic range of >10(10),
      which, to our best knowledge, is the first demonstration of an SSCC with a
      dynamic range comparable to that of commercial DSCCs. The comparison of high
      dynamic measurement performances between SSCC and a standard DSCC (Sequoia,
      Amplitude Technologies) is also carried out on a 200 TW Ti:sapphire laser, and
      the consistency of results verifies the veracity of our SSCC. 

PMID- 24448652
TI  - Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux
      esophagitis with morning or nighttime dosing.
AB  - BACKGROUND: Morning dose or twice-daily proton pump inhibitor (PPI) use is often
      prescribed to heal severe reflux esophagitis. AIM: Compare the effect of single
      dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium
      bicarbonate (Zegerid((r))) (IR-OME) on esophagitis and gastroesophageal reflux
      symptoms. METHODS: Adult outpatients with Los Angeles grade C or D esophagitis
      were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a
      prospective, randomized, parallel design, single center study.
      Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires
      were completed at baseline and follow-up. Intention-to-treat and per-protocol
      analyses were performed. RESULTS: Ninety-two of 128 (72 %) eligible subjects
      participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21
      51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved
      [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night)
      in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77
      vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of
      newly identified Barrett's esophagus was 14 % with half diagnosed only after
      treatment. CONCLUSIONS: Once-daily IR-OME (taken morning or night) effectively
      heals severe reflux esophagitis and improves GERD symptoms. Results support the
      clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in
      severe esophagitis patients to assure healing and exclude Barrett's esophagus.

PMID- 24448656
TI  - Novel mesoporous Si@C microspheres as anodes for lithium-ion batteries.
AB  - In this paper, we demonstrate the design and synthesis of novel mesoporous Si@C
      microspheres as anode materials for high-performance lithium-ion batteries. SiO2
      nanoparticles modified with hexadecyl trimethyl ammonium bromide are enveloped
      within resorcinol-formaldehyde polymer microspheres which form in the ethanol
      water-ammonia system. Mesoporous voids between Si nanoparticles and the carbon
      framework are generated after carbonization at 800  degrees C and magnesiothermic
      reduction at 650  degrees C. The resultant Si@C microspheres show regular
      spherical shapes with a mean diameter of about 500 nm, a mesopore size of 3.2 nm
      and specific surface areas of 401-424 m(2) g(-1). Mesoporosity of Si@C
      microspheres effectively buffers the volume expansion/shrinkage of Si
      nanoparticles during Li ion insertion/extraction, which endows mesoporous Si@C
      microspheres with excellent electrochemical performance and cycle stability when
      they are used as lithium-ion battery anode materials. A typical sample of
      mesoporous Si@C microspheres presents a specific capacity of 1637 and 1375 mA h
      g(-1) at first discharge and charge under a current density of 50 mA g(-1). After
      100 cycles, the charge capacity remains 1053 mA h g(-1) with a coulombic
      efficiency of 99%, showing good cycle stability of the anode. This finding
      highlights the potential application of mesoporous Si@C microspheres in lithium
      ion battery anode materials. 

PMID- 24448657
TI  - Defining and detecting structural sensitivity in biological models: developing a
      new framework.
AB  - When we construct mathematical models to represent biological systems, there is
      always uncertainty with regards to the model specification--whether with respect
      to the parameters or to the formulation of model functions. Sometimes choosing
      two different functions with close shapes in a model can result in substantially
      different model predictions: a phenomenon known in the literature as structural
      sensitivity, which is a significant obstacle to improving the predictive power of
      biological models. In this paper, we revisit the general definition of structural
      sensitivity, compare several more specific definitions and discuss their
      usefulness for the construction and analysis of biological models. Then we
      propose a general approach to reveal structural sensitivity with regards to
      certain system properties, which considers infinite-dimensional neighbourhoods of
      the model functions: a far more powerful technique than the conventional approach
      of varying parameters for a fixed functional form. In particular, we suggest a
      rigorous method to unearth sensitivity with respect to the local stability of
      systems' equilibrium points. We present a method for specifying the neighbourhood
      of a general unknown function with [Formula: see text] inflection points in terms
      of a finite number of local function properties, and provide a rigorous proof of
      its completeness. Using this powerful result, we implement our method to explore
      sensitivity in several well-known multicomponent ecological models and
      demonstrate the existence of structural sensitivity in these models. Finally, we
      argue that structural sensitivity is an important intrinsic property of
      biological models, and a direct consequence of the complexity of the underlying
      real systems.

PMID- 24448658
TI  - Coding sequence density estimation via topological pressure.
AB  - We give a new approach to coding sequence (CDS) density estimation in genomic
      analysis based on the topological pressure, which we develop from a well known
      concept in ergodic theory. Topological pressure measures the 'weighted
      information content' of a finite word, and incorporates 64 parameters which can
      be interpreted as a choice of weight for each nucleotide triplet. We train the
      parameters so that the topological pressure fits the observed coding sequence
      density on the human genome, and use this to give ab initio predictions of CDS
      density over windows of size around 66,000 bp on the genomes of Mus Musculus,
      Rhesus Macaque and Drososphilia Melanogaster. While the differences between these
      genomes are too great to expect that training on the human genome could predict,
      for example, the exact locations of genes, we demonstrate that our method gives
      reasonable estimates for the 'coarse scale' problem of predicting CDS density.
      Inspired again by ergodic theory, the weightings of the nucleotide triplets
      obtained from our training procedure are used to define a probability
      distribution on finite sequences, which can be used to distinguish between intron
      and exon sequences from the human genome of lengths between 750 and 5,000 bp. At
      the end of the paper, we explain the theoretical underpinning for our approach,
      which is the theory of Thermodynamic Formalism from the dynamical systems
      literature. Mathematica and MATLAB implementations of our method are available at
      http://sourceforge.net/projects/topologicalpres/ .

PMID- 24448659
TI  - Expression of microRNAs and their targets regulates floral development in tobacco
      (Nicotiana tabacum).
AB  - MicroRNAs (miRNAs) are an extensive class of endogenous posttranscriptional gene
      regulators that function to mediate gene expression by cleaving target mRNAs or
      by preventing protein translation. Because of their importance in mediating gene
      regulation, identifying and elucidating the function of miRNAs have been the
      primary focus of many researchers. Now that many miRNAs have been identified and
      assessed for their functionality, the next step is to create expression profiles
      for miRNAs, so that gene expression studies can be further enhanced with
      knowledge of the basal expression levels of miRNAs and their targets. In a
      previous study, 259 putative miRNAs were identified in tobacco, in which 11 of
      them were confirmed. The primary goal of this study was to further expand on that
      study and create an expression profile for nine miRNAs and their targets in a
      tissue-specific manner in tobacco. We chose to study miRNAs that largely play a
      role in floral development and nutrient stress response. The results of our study
      show that all tested miRNAs and their targets were expressed in a differential
      manner. The results of our study also show that out of the tested miRNAs and
      their targets, miR159, miR157, miR167, miR172, and superoxide dismutase were
      expressed the highest, suggesting that these genes may play a vital role in the
      growth and development of tobacco. Corrected expression of miRNAs and their
      targets regulates floral development. 

PMID- 24448661
TI  - MicroRNA-143 regulates adipogenesis by modulating the MAP2K5-ERK5 signaling.
AB  - A better understanding of the molecular mechanisms that regulate adipose tissue
      derived stromal cell (ADSC) differentiation could provide new insight into some
      adipose-tissue-related disease. The differentiation of ADSCs into adipocytes is a
      complex physiological process that includes clonal expansion, growth arrest, and
      terminal differentiation. Here the role of microRNA-143 (miR-143) during ADSC
      adipogenic differentiation was systematically investigated. We found that miR-143
      expression was transiently decreased after adipogenic induction while increased
      from day 3 and peaked on day 7 after induction. We show for the first time that
      the role of miR-143 is not consistent in the differentiation process. The
      regulatory role depends on the differentiation stage that miR-143 acts on. When
      miR-143 is overexpressed during the clonal expansion stage, the adipogenic
      differentiation of ADSCs is inhibited, whereas the overexpression of miR-143
      during the growth arrest stage or terminal differentiation stage promotes
      differentiation. Further we firstly demonstrate that miR-143 plays the
      modulational role by directly repressing MAP2K5, a key member of the MAPKK family
      in the MAPK signaling pathway. These findings suggest that miR-143 plays an
      important role in adipose tissue formation, with special implications for some
      metabolic disease in which the amount and/or function of adipose tissue is
      altered. 

PMID- 24448662
TI  - Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma
      tumors.
AB  - Here we report the identification of a proliferative, viable, and hyperdiploid
      tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using
      xenograft tumor models, we demonstrate that hyperdiploid cell populations are
      maintained in xenograft tumors and that clonally expanded hyperdiploid cells
      support tumor formation and progression in vivo. In some patient tumorsphere
      lines, hyperdiploidy is maintained during long-term culture and in vivo within
      xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state.
      In other patient lines hyperdiploid cells display genetic drift in vitro and in
      vivo, suggesting that in these patients hyperdiploidy is a transient cell state
      that generates novel phenotypes, potentially facilitating rapid tumor evolution.
      We show that the hyperdiploid cells are resistant to conventional therapy, in
      part due to infrequent cell division due to a delay in the G0/G1 phase of the
      cell cycle. Hyperdiploid tumor cells are significantly larger and more
      metabolically active than euploid cancer cells, and this correlates to an
      increased sensitivity to the effects of glycolysis inhibition. Together these
      data identify GB hyperdiploid tumor cells as a potentially important
      subpopulation of cells that are well positioned to contribute to tumor evolution
      and disease recurrence in adult brain cancer patients, and suggest tumor
      metabolism as a promising point of therapeutic intervention against this
      subpopulation.

PMID- 24448663
TI  - Enantioselective synthesis of helical polydiacetylenes in the visible light
      region.
AB  - Herein, we demonstrate for the first time that the enantio-selective
      polymerization of DA monomers could be realized upon irradiation with circularly
      polarized visible light (CPVL), which could effectively provide chiral order in
      the propagating step of a polymerization reaction. 

PMID- 24448664
TI  - Identification and optimization of short helical peptides with novel reactive
      functionality as catalysts for acyl transfer by reactive tagging.
AB  - Herein we describe the screening and subsequent optimization of peptide catalysts
      for ester activation. A combinatorial methodology using dye-tagged substrate
      analogs is described for determining which components of a His-containing helical
      library display acyl transfer activity. We found that helical peptides display
      high activity, and amino acids that reinforce this propensity are advantaged.
      Through this approach two new structural motifs have been discovered that are
      capable of activating esters in organic solvents. Unlike most acyl transfer
      catalysts functioning in organic solvents, these catalysts are histidine- rather
      than N-alkyl histidine-based. Longer peptides with localization of reactive
      groups on the C-terminal end of the peptide were found to further enhance
      catalytic activity up to ~2800-fold over background. 

PMID- 24448665
TI  - Isolation, expansion and characterization of bone marrow-derived mesenchymal
      stromal cells in serum-free conditions.
AB  - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) heralded a new beginning
      for regenerative medicine and generated tremendous interest as the most promising
      source for therapeutic application. Most cell therapies require stringent
      regulatory compliance and prefer the use of serum-free media (SFM) or xeno-free
      media (XFM) for the MSC production process, starting from the isolation onwards.
      Here, we report on serum-free isolation and expansion of MSCs and compare them
      with cells grown in conventional fetal bovine serum (FBS)-containing media as a
      control. The isolation, proliferation and morphology analysis demonstrated
      significant differences between MSCs cultured in various SFM/XFM in addition to
      their difference with FBS controls. BD MosaicTM Mesenchymal Stem Cell Serum-Free
      media (BD-SFM) and Mesencult-XF (MSX) supported the isolation, sequential
      passaging, tri-lineage differentiation potential and acceptable surface marker
      expression profile of BM-MSCs. Further, MSCs cultured in SFM showed higher immune
      suppression and hypo-immunogenicity properties, making them an ideal candidate
      for allogeneic cell therapy. Although cells cultured in control media have a
      significantly higher proliferation rate, BM-MSCs cultured in BD-SFM or MSX media
      are the preferred choice to meet regulatory requirements as they do not contain
      bovine serum. While BM-MSCs cultured in BD-SFM and MSX media adhered to all MSC
      characteristics, in the case of few parameters, the performance of cells cultured
      in BD-SFM was superior to that of MSX media. Pre-clinical safety and efficiency
      studies are required before qualifying SFM or XFM media-derived MSCs for
      therapeutic applications.

PMID- 24448667
TI  - Efficacy of fluorescence diagnosis-guided Mohs micrographic surgery for pigmented
      vs non-pigmented basal cell carcinoma.
AB  - Pigmented basal cell carcinoma (PBCC) occurs more frequently in Asian population.
      The efficacy of fluorescence diagnosis (FD) for PBCCs treated with Mohs
      micrographic surgery has not yet been determined. This study enrolled 255
      patients with 258 biopsy-proven BCC lesions: 199 PBCCs (77.1%) and 59 non-PBCCs
      (22.9%). We compared the clinicopathological and surgical features of the PBCCs
      and non-PBCCs. Each group was divided into 2 sub-groups, those assessed and not
      assessed by FD, to retrospectively analyse surgical features. Aggressive
      histological subtypes were less prevalent in PBCCs than in non-PBCCs. PBCCs
      required significantly fewer stages of Mohs excision, with significantly smaller
      surgical margins and surgical depth, than non-PBCCs. FD did not confer any
      benefits on PBCCs during Mohs micrographic surgery. However, non-PBCCs assessed
      by FD required significantly fewer Mohs stages, with significantly smaller
      surgical margins, than lesions not assessed by FD. These findings suggest that FD
      should be performed before Mohs micrographic surgery to delineate the margins of
      non-PBCCs in Asians.

PMID- 24448666
TI  - [Diagnostics of benign ductal epithelial cell proliferation of the breast in
      biopsy material].
AB  - The pathological evaluation of radiological or sonographical abnormalities by
      needle core biopsy of the breast frequently involves the differential diagnosis
      of benign epithelial cell proliferations. The lesions to be considered include
      usual type and atypical ductal epithelial cell hyperplasia, columnar cell changes
      including flat epithelial cell atypia, the spectrum of hyperplastic and atypical
      apocrine epithelial cell proliferations and papillary lesions. This review
      provides an overview of the diagnostic criteria, the current terminology and the
      differential diagnosis of these lesions. The clinical management and the
      prognosis of the lesions are discussed. 

PMID- 24448669
TI  - Determination of paroxetine in blood and urine using micellar liquid
      chromatography with electrochemical detection.
AB  - Paroxetine is a potent selective serotonin reuptake inhibitor used for the
      treatment of depression and related mood disorders. A micellar liquid
      chromatographic method was developed for the determination of paroxetine in serum
      and urine. Detection of paroxetine was carried out using a C18 column and a
      mobile phase of 0.15 M sodium dodecyl sulfate, 6% 1-pentanol at pH 3 (buffer salt
      0.01 M NaH2PO4) running under isocratic mode at 1.0 mL/min and electrochemical
      detection at 0.8 V. The analyte was eluted without interferences in <15 min. The
      proposed methodology was validated under the guidelines of the International
      Conference on Harmonization of Technical Requirements for Registration of
      Pharmaceuticals for Human Use in matrix in terms of specificity, linearity (r(2)
      > 0.9999; 0.5-5 MUg/mL range), accuracy (88-97.5%, recovery), repeatability (RSD
      < 0.54%), intermediate precision (RSD < 0.54%), limit of detection and
      quantification (0.001 and 0.005 MUg/mL, respectively) and robustness (RSD <
      3.63%). Developed method was successfully applied to real blood and urine samples
      as well as in spiked serum and urine samples. The developed method was specific,
      rapid, precise, reliable, accurate, inexpensive and then suitable for routine
      analysis of paroxetine in monitorized samples.

PMID- 24448668
TI  - Development of a composite chiral stationary phase from BSA and beta-cyclodextrin
      bonded silica.
AB  - A composite chiral stationary phase (CSP) derived from bovine serum albumin (BSA)
      and beta-cyclodextrin (CD)-bonded silica was prepared. 2,4,6-Trichloro-1,3,5
      triazine was used as a cross-linker. The obtained CSP was applied to the
      enantioseparation of tryptophan, hydrobenzoin, phenylalanine and mandelic acid.
      The influences of eluent pH value, organic modifier and column temperature on the
      retention and enantioseparation were discussed. Tryptophan and hydrobenzoin
      achieved excellent resolution on the composite CSP. For tryptophan, the highest
      selectivity, 2.79, was achieved with 1% of methanol at pH 8.0. For hydrobenzoin,
      the selectivity could reach 1.42. The chromatographic results were compared with
      that on beta-CD-bonded or BSA-immobilized CSP.

PMID- 24448670
TI  - Development of ruthenium(II) complexes as topical antibiotics against methicillin
      resistant Staphylococcus aureus.
AB  - A series of ruthenium(II) bis(2,2'-bipyridyl) complexes containing N-phenyl
      substituted diazafluorenes (Ru-C1, Ru-C6, Ru-C7 and Ru-F) was synthesized and
      their potential antibacterial activity against methicillin resistant
      Staphylococcus aureus (MRSA) was investigated. The Ru-C7 complex showed
      significant improvement in both minimum inhibitory concentration (MIC, 6.25 MUg
      mL(-1)) and minimum bactericidal concentration (MBC, 25 MUg mL(-1)) towards MRSA
      when compared with those of methicillin (positive control) (MIC = 25 MUg mL(-1)
      and MBC = 100 MUg mL(-1)). The Ru-C7 complex possessed much stronger
      antibacterial effects than the Ru-C6 complex (MIC, 25 MUg mL(-1), MBC, >100 MUg
      mL(-1)). Both Ru-C6 and Ru-C7 complexes were also demonstrated to be biologically
      safe when tested on normal human skin keratinocytes.

PMID- 24448671
TI  - Differences in indicators of malignancy between luminal epithelial cell type and
      myoepithelial cell type of simple solid carcinoma in the canine mammary gland.
AB  - Routinely diagnosed simple solid carcinoma (SSC) of the canine mammary gland
      comprises a heterogeneous group of tumors. Seventy-two cases that had been
      diagnosed as SSC based on hematoxylin and eosin-stained tissue sections were
      reclassified immunohistochemically on the basis of myoepithelial markers p63 and
      alpha-smooth muscle actin, as well as a luminal epithelial marker cytokeratin 8.
      Only 23 cases (32%) were true SSC, composed only of luminal epithelial cells,
      whereas 11 cases (15%) were malignant myoepithelioma (MM), composed predominantly
      of myoepithelial cells, and 38 cases (53%) were biphasic carcinoma (BC),
      characterized by biphasic proliferation of luminal epithelial and
      basal/myoepithelial components. As the pathological parameters were compared
      between the reclassified tumor types, infiltrative potential, vascular/lymphatic
      invasion, lymph node metastasis, and Ki-67 labeling index were higher in true SSC
      compared with MM and BC, suggesting that the former may exhibit a poorer
      prognosis compared with the latter two. 

PMID- 24448672
TI  - Establishment of a rat model for canine necrotizing meningoencephalitis (NME).
AB  - The pathogenesis of necrotizing meningoencephalitis (NME), necrotizing
      leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) is
      still uncertain, although they are considered immune-mediated diseases. The
      purpose of the present study is to generate a rodent model(s) of these diseases.
      Rats were injected with rat cerebral or cerebellar homogenate. Rats injected with
      cerebral homogenate (Cbr) exhibited vacuolar or malacic changes mainly in the
      cerebral cortex. CD3-positive T cells and Iba-1-positive and CD163-negative
      microglia infiltrated and activated around the lesions. IgG deposited in the
      glial fibrillary acid protein (GFAP)-positive glia limitans from the early phase,
      and CD3-positive T cells attached to GFAP-positive astrocytes. Autoantibodies
      against GFAP were detected in the sera. These pathological features of Cbr rats
      were consistent with those of canine NME. In contrast, rats injected with
      cerebral homogenate (Cbe) exhibited demyelinating lesions with inflammatory
      reactions in the cerebellum, brainstem, and spinal cord. The presence of
      demyelination and autoantibodies against myelin proteins in Cbe rats was similar
      to murine experimental autoimmune encephalitis and differed from NME, NLE, and
      GME. All the present findings indicate that autoantibodies together with
      microglia and T cells may play a major role in the pathogenesis of idiopathic
      canine meningoencephalomyelitis. 

PMID- 24448673
TI  - The reactions of Criegee intermediates with alkenes, ozone, and carbonyl oxides.
AB  - The reaction of Criegee intermediates with a number of coreactants is examined
      using theoretical methodologies, combining ROCCSD(T)//M06-2X quantum calculations
      with theoretical kinetic predictions of the rate coefficients. The reaction of CI
      with alkenes is found to depend strongly on the substitutions in the reactants,
      resulting in significant differences in the predicted rate coefficient as a
      function of the selected alkene and CI. Despite submerged barriers, these
      entropically disfavored reactions are not expected to affect CI chemistry. The
      reaction of H2COO + H2COO is found to be barrierless, with a rate coefficient
      nearing the collision limit, >=4 * 10(-11) cm(3) molecule(-1) s(-1). The dominant
      reaction products are expected to be carbonyl compounds and an oxygen molecule,
      though chemically activated reactions may give rise to a plethora of different
      (per)acids and carbonyl compounds. CI + CI reactions are expected to be important
      only in laboratory environments with high CI concentrations. The reaction of
      H2COO with O3 was predicted to proceed through a pre-reactive complex and a
      submerged barrier, with a rate coefficient of 1 * 10(-12) cm(3) molecule(-1) s(
      1). A study of the dominant CI reactions under experimental and atmospheric
      conditions shows that the latter reaction might affect CI chemistry. 

PMID- 24448674
TI  - Field realistic doses of pesticide imidacloprid reduce bumblebee pollen foraging
      efficiency.
AB  - Bumblebees and other pollinators provide a vital ecosystem service for the
      agricultural sector. Recent studies however have suggested that exposure to
      systemic neonicotinoid insecticides in flowering crops has sub-lethal effects on
      the bumblebee workforce, and hence in reducing queen production. The mechanism
      behind reduced nest performance, however, remains unclear. Here we use Radio
      Frequency Identification (RFID) technology to test whether exposure to a low,
      field realistic dose (0.7 ppb in sugar water and 6 ppb in pollen) of the
      neonicotinoid imidacloprid, reduces worker foraging efficiency. Whilst the nectar
      foraging efficiency of bees treated with imidacloprid was not significantly
      different than that of control bees, treated bees brought back pollen less often
      than control bees (40 % of trips vs 63 % trips, respectively) and, where pollen
      was collected, treated bees brought back 31 % less pollen per hour than controls.
      This study demonstrates that field-realistic doses of these pesticides
      substantially impacts on foraging ability of bumblebee workers when collecting
      pollen, and we suggest that this provides a causal mechanism behind reduced queen
      production in imidacloprid exposed colonies. 

PMID- 24448675
TI  - Investigating wild berries as a dietary approach to reducing the formation of
      advanced glycation endproducts: chemical correlates of in vitro antiglycation
      activity.
AB  - Evidence supports the health promoting benefits of berries, particularly with
      regard to the prevention and management of chronic diseases such cardio- and
      cerebrovascular disease, diabetes and Alzheimer's disease. Two related
      pathophysiological features common to many of these conditions are oxidative
      stress and the accumulation of advanced glycation endproducts (AGEs). Whereas
      antioxidant properties are well-established in several species of berries and are
      believed central to their protective mechanisms, few studies have investigated
      the effects of berries on AGE formation. Here, employing a series of
      complementary in vitro assays, we evaluated a collection of wild berry extracts
      for 1) inhibitory effects on fluorescent-AGE and Nepsilon- (carboxymethyl)lysine
      albumin adduct formation, 2) radical scavenging activity and 3) total phenolic
      and anthocyanin content. All samples reduced AGE formation in a concentration
      dependent manner that correlated positively with each extract's total phenolic
      content and, to a lesser degree, total anthocyanin content. Inhibition of AGE
      formation was similarly related to radical scavenging activities. Adding
      antiglycation activity to the list of established functional properties ascribed
      to berries and their phenolic metabolites, our data provide further insight into
      the active compounds and protective mechanisms through which berry consumption
      may aid in the prevention and treatment of chronic diseases associated with AGE
      accumulation and toxicity. As widely available, safe and nutritious foods,
      berries represent a promising dietary intervention worthy of further
      investigation. 

PMID- 24448677
TI  - The South China and North Vietnam ECTA branches.

PMID- 24448676
TI  - An evidence-based knowledgebase of pulmonary arterial hypertension to identify
      genes and pathways relevant to pathogenesis.
AB  - Pulmonary arterial hypertension (PAH) is a major progressive form of pulmonary
      hypertension (PH) with more than 4800 patients in the United States. In the last
      two decades, many studies have identified numerous genes associated with this
      disease. However, there is no comprehensive research resource for PAH or other PH
      types that integrates various genetic studies and their related biological
      information. Thus, the number of associated genes, and their strength of
      evidence, is unclear. In this study, we tested the hypothesis that a web-based
      knowledgebase could be used to develop a biological map of highly interrelated,
      functionally important genes in PAH. We developed the pulmonary arterial
      hypertension knowledgebase (PAHKB, ), a comprehensive database with a user
      friendly web interface. PAHKB extracts genetic data from all available sources,
      including those from association studies, genetic mutation, gene expression,
      animal model, supporting literature, various genomic annotations, gene networks,
      cellular and regulatory pathways, as well as microRNAs. Moreover, PAHKB provides
      online tools for data browsing and searching, data integration, pathway graphical
      presentation, and gene ranking. In the current release, PAHKB contains 341 human
      PH-related genes (293 protein coding and 48 non-coding genes) curated from over
      1000 PubMed abstracts. Based on the top 39 ranked PAH-related genes in PAHKB, we
      constructed a core biological map. This core map was enriched with the TGF-beta
      signaling pathway, focal adhesion, cytokine-cytokine receptor interaction, and
      MAPK signaling. In addition, the reconstructed map elucidates several novel
      cancer signaling pathways, which may provide clues to support the application of
      anti-cancer therapeutics to PAH. In summary, we have developed a system for the
      identification of core PH-related genes and identified critical signaling
      pathways that may be relevant to PAH pathogenesis. This system can be easily
      applied to other pulmonary diseases. 

PMID- 24448678
TI  - Systematic review of open techniques for parastomal hernia repair.
AB  - Parastomal hernia formation is common following formation of an abdominal stoma,
      with the risk of subsequent incarceration, obstruction and strangulation. Current
      treatment options include non-operative management, stoma relocation and fascial
      repair with or without mesh. The purpose of this systematic review was to
      evaluate the effectiveness and safety of open mesh repair of a parastomal hernia
      and to compare open non-mesh fascial repair with mesh techniques of parastomal
      hernia repair. Electronic databases were searched for studies comparing the two
      surgical techniques in accordance with preferred reporting items for systematic
      reviews and meta-analyses. The primary outcome of the study was the comparison of
      recurrence rates of parastomal hernia for each technique. Secondary outcomes
      included comparison of mortality, wound infection, mesh infection and any other
      complication. Twenty-seven studies of parastomal hernia repair were included and
      divided into two subgroups for open mesh repair and non-mesh fascial repair. Non
      mesh fascial repair resulted in a high recurrence rate (around 50%). Reported
      recurrence rates for mesh repair were substantially lower, at 7.9-14.8%,
      depending on the position of the mesh in relation to the abdominal fascia and the
      length of follow-up. Morbidity and mortality did not differ significantly between
      the techniques used to repair a parastomal hernia. This study shows that mesh
      repair of a parastomal hernia is safe and significantly reduces the rate of
      recurrence compared with sutured repair, which should only be used in exceptional
      circumstances. There is insufficient evidence to determine which mesh technique
      (onlay, sublay or underlay) is most successful in terms of recurrence rates and
      morbidity.

PMID- 24448679
TI  - Comparison of LDL-cholesterol estimate using the Friedewald formula and the newly
      proposed de Cordova formula with a directly measured LDL-cholesterol in a healthy
      South African population.
AB  - BACKGROUND: The accurate determination of low density lipoprotein cholesterol
      (LDL-c) is pertinent in clinical practice. Most laboratories employ the
      Friedewald formula, for convenient estimation of LDL-c, despite its shortfalls.
      Different formulae have been proposed for use, for more accurate but convenient
      estimation of LDL-c. Here, we compare a new formula recently proposed by de
      Cordova et al., with that of Friedewald and LDL-c determined by a homogeneous
      assay. We also assess its performance at very low TG levels against the modified
      Friedewald formula recommended by Ahmadi et al. METHODS: A database of 587 adults
      from the 'Establishing Reference Intervals for Selected Analytes in South Africa'
      study was utilized. Fasting samples were assayed for lipids. LDL-c was determined
      by the Daiichi method. Performance of the Friedewald and the de Cordova formulae
      was compared. This was exclusively repeated at very low TG levels (<1.13 mmol/L),
      this time, including the Ahmadi formula. RESULTS: The Friedewald formula and the
      de Cordova formula both had high correlations with the direct LDL-c (r = 0.98 and
      r = 0.97, respectively), although the latter showed an inconsistent bias at
      different LDL-c levels. The two formulae had a higher correlation (r = 0.98) than
      the Ahmadi formula (r = 0.92) at very low TG levels. CONCLUSIONS: The Friedewald
      formula showed better agreement with the direct LDL-c than the de Cordova
      formula, at various LDL-c levels, in our population. It also performed better
      than the Ahmadi formula at very low TG levels. We therefore advise that it
      remains the formula of choice for LDL-c estimation in South Africa.

PMID- 24448680
TI  - Charge separation at disordered semiconductor heterojunctions from random walk
      numerical simulations.
AB  - Many recent advances in novel solar cell technologies are based on charge
      separation in disordered semiconductor heterojunctions. In this work we use the
      Random Walk Numerical Simulation (RWNS) method to model the dynamics of electrons
      and holes in two disordered semiconductors in contact. Miller-Abrahams hopping
      rates and a tunnelling distance-dependent electron-hole annihilation mechanism
      are used to model transport and recombination, respectively. To test the validity
      of the model, three numerical "experiments" have been devised: (1) in the absence
      of constant illumination, charge separation has been quantified by computing
      surface photovoltage (SPV) transients. (2) By applying a continuous generation of
      electron-hole pairs, the model can be used to simulate a solar cell under steady
      state conditions. This has been exploited to calculate open-circuit voltages and
      recombination currents for an archetypical bulk heterojunction solar cell (BHJ).
      (3) The calculations have been extended to nanostructured solar cells with
      inorganic sensitizers to study, specifically, non-ideality in the recombination
      rate. The RWNS model in combination with exponential disorder and an activated
      tunnelling mechanism for transport and recombination is shown to reproduce
      correctly charge separation parameters in these three "experiments". This
      provides a theoretical basis to study relevant features of novel solar cell
      technologies. 

PMID- 24448681
TI  - Ultrasound evaluation of greater trochanter pain syndrome in patients with
      spondyloarthritis: are there any specific features?
AB  - Although greater trochanter pain syndrome (GTPS) is a prevalent cause of
      musculoskeletal pain in the general population, there is lack of imaging studies
      searching for differential features of inflammatory enthesitis in GTPS. We
      analyzed the features of GTPS using sonography and magnetic resonance imaging
      (MRI) to identify useful differential signs between spondyloarthritis (SpA) and
      other inflammatory or non-inflammatory musculoskeletal diseases. All patients
      with unilateral GTPS attended by our Arthritis Unit between February 2011 and
      March 2012 were included. Patients were classified as having SpA or mechanical
      (without inflammatory musculoskeletal disease) GTPS. Rheumatoid arthritis (RA)
      patients were also included as inflammatory controls. Ultrasound scans of the
      painful and contralateral, asymptomatic, greater trochanter were made. We
      assessed the gluteus medius and gluteus minimus tendons for signs suggestive of
      tendinopathy. Random MRI of the same regions was made in a subgroup of patients
      to validate the ultrasound findings. A total of 107 patients with unilateral GTPS
      were included, of whom 96 were female, with a mean age of 61.6 years: 34 had SpA,
      48 had non-inflammatory musculoskeletal disease, and 25 had RA. No specific
      sonographic features for SpA were found. Pathological findings were more frequent
      in patients without musculoskeletal inflammatory disease (mainly bursitis and
      erosions). A large number of alterations were found in the asymptomatic side
      (around 40 % had cortical irregularities and 20 % bursa effusion). Signs of
      enthesopathy were more prevalent in the gluteus minimus tendon, regardless of the
      diagnosis (54.2 % had erosions, 39.3 % bursitis, 38.3 % calcifications and 37.4 %
      tendinosis). No patient had power Doppler signal. Age was the main factor in the
      appearance of tendinopathy. MRI confirmed the changes detected by ultrasound in
      all 40 patients evaluated. GTPS in patients with SpA has similar sonographic
      findings to those observed in patients with RA and patients without
      musculoskeletal inflammatory disease. Neither sonography nor MRI was clinically
      useful in classifying GTPS as a manifestation of SpA.

PMID- 24448682
TI  - NMR elucidation of the role of Mg2+ in the structure and stability of the
      conserved RNA motifs of the EMCV IRES element.
AB  - The three dimensional solution structures of a highly conserved 16mer RNA,
      endowed with a classic 'GNRA' tetraloop motif, and a 17mer RNA containing a
      cytosine-rich heptaloop which is predicted to be a potential receptor for the
      former RNA, of the I-domain of Encephalomyocarditis virus IRES have been
      determined by NMR spectroscopy. As Mg(2+) plays an important role in the activity
      of the IRES, the corresponding NMR structures of the Mg(2+) bound RNA complexes
      have also been determined. These RNA NMR structures, 16mer (21 constraints per
      residue), 16mer RNA/Mg(2+) (21 constraints per residue), 17mer (17 constraints
      per residue) and 17mer RNA/Mg(2+) (16 constraints per residue), were calculated
      to a high degree of precision with low RMSDs and low clash scores represent, to
      the best our knowledge, the first structures of a type II picornavirus IRES.
      Conformational analysis of the average structure showed that the RNAs and their
      Mg(2+) complexes adopt characteristic A-form helical structures, stabilised by
      canonical and non-canonical interactions in both the stem and loop regions. The
      GCGA tetraloop of the 16mer folds into a standard GNRA conformation, with the
      structural role of A550 being in the form of a G547.A550 sheared base-pair made
      up of two hydrogen bonds. Further, the previously uncharacterised AACCCCA
      heptaloop present in the 17mer forms a compact tertiary loop motif, held together
      by strong pi-pi interactions. Analysis of the NMR structures demonstrates that
      the role of Mg(2+) is principally to confer enhanced stability to the RNAs
      whereby the tetra- and heptaloops can achieve optimum conformation for any RNA
      RNA interactions which are crucial for understanding the structure-function
      relationship of the IRES. 

PMID- 24448683
TI  - One-step synthesis of sulfur doped graphene foam for oxygen reduction reactions.
AB  - Sulfur doped graphene foam has been successfully synthesized by a simple solve
      thermal method, which exhibited a much enhanced oxygen reduction reaction (ORR)
      catalytic activity as well as an especially high electrochemical stability, and
      would be a promising non-metal cathode catalyst for the ORR. 

PMID- 24448684
TI  - Understanding the relative importance of preserving functional abilities in
      Alzheimer's disease in the United States and Germany.
AB  - PURPOSE: To estimate the relative importance that Alzheimer's disease (AD)
      caregivers in the United States and Germany place on preserving patients' ability
      to perform activities of daily living. METHODS: US and German residents providing
      care for a person with AD completed an online preference survey. Each respondent
      completed five best-worst scaling questions. Each question related to five of 10
      activities from the Disability Assessment for Dementia scale. Preference weights,
      indicating the relative importance of preserving the ability to perform these 10
      activities for 36 months, were estimated using maximum-difference scaling. A
      separate model was estimated for each country. RESULTS: Four hundred and three US
      and 400 German caregivers completed the survey. In both countries, preserving a
      patients' ability to use the toilet without accidents was the most important
      activity and handling money was the least important activity. There were few
      differences between US and German caregivers in the relative importance across
      activities. CONCLUSIONS: Caregivers generally placed greater importance on
      preserving basic activities of daily living than on preserving instrumental
      activities of daily living. Understanding differences in the relative importance
      of functional items in the DAD may contribute to a better understanding of the
      benefits of different AD treatment and support measures.

PMID- 24448685
TI  - Profiles, sources, and transport of polycyclic aromatic hydrocarbons in soils
      affected by electronic waste recycling in Longtang, south China.
AB  - We studied the profiles, possible sources, and transport of polycyclic aromatic
      hydrocarbons (PAHs) in soils from the Longtang area, which is an electronic waste
      (e-waste) recycling center in south China. The sum of 16 PAH concentrations
      ranged from 25 to 4,300 ng/g (dry weight basis) in the following order: pond
      sediment sites (77 ng/g), vegetable fields (129 ng/g), paddy fields (180 ng/g),
      wastelands (258 ng/g), dismantling sites (678 ng/g), and former open burning
      sites (2,340 ng/g). Naphthalene, phenanthrene, fluoranthene, pyrene, chrysene,
      and benzo[b]fluoranthene were the dominant PAHs and accounted for approximately
      75 % of the total PAHs. The similar composition characteristics of PAHs and the
      significant correlations among individual, low molecular weight, high molecular
      weight, and total PAHs were found in all six sampling site types, thus indicating
      that PAHs originated from similar sources. The results of both isomeric ratios
      and principal component analyses confirmed that PAHs were mainly derived from the
      incomplete combustion of e-waste. The former open burning sites and dismantling
      sites were the main sources of PAHs. Soil samples that were taken closer to the
      point sources had high PAH concentrations. PAHs are transported via different
      soil profiles, including those in agricultural fields, and have been detected not
      only in 0- to 40-cm-deep soil but also in 40 cm to 80 cm-deep soil. PAH
      concentrations in soils in Longtang have been strongly affected by primitive e
      waste recycling, particularly by former open burning activities.

PMID- 24448686
TI  - P-cadherin promotes ovarian cancer dissemination through tumor cell aggregation
      and tumor-peritoneum interactions.
AB  - More than 60% of patients who are diagnosed with epithelial ovarian cancer (EOC)
      present with extensive peritoneal carcinomatosis. EOC cells typically disseminate
      by shedding into the peritoneal fluid in which they survive as multicellular
      aggregates and then implant onto peritoneal surfaces. However, the mechanism that
      facilitates aggregation and implantation of EOC cells is poorly understood. The
      cell adhesion molecule P-cadherin has been reported to be induced during early
      progression of EOC and to promote tumor cell migration. In this study, P-cadherin
      not only promoted migration of EOC cells, but also facilitated the assembly of
      floating EOC cells into multicellular aggregates and inhibited anoikis in vitro.
      Furthermore, inhibiting P-cadherin by short hairpin RNAs (shRNA) or a
      neutralizing antibody prevented EOC cells from attaching to peritoneal
      mesothelial cells in vitro. In mouse intraperitoneal xenograft models of EOC,
      inhibition of P-cadherin decreased the aggregation and survival of floating tumor
      cells in ascites and reduced the number of tumor implants on peritoneal surfaces.
      These findings indicate that P-cadherin promotes intraperitoneal dissemination of
      EOC by facilitating tumor cell aggregation and tumor-peritoneum interactions in
      addition to promoting tumor cell migration. IMPLICATIONS: Inhibiting P-cadherin
      blocks multiple key steps of EOC progression and has therapeutic potential.

PMID- 24448687
TI  - Utilization of liquid chromatography mass spectrometry analyses to identify LKB1
      APC interaction in modulating Wnt/beta-catenin pathway of lung cancer cells.
AB  - STK11/LKB1, a serine/threonine protein kinase and tumor suppressor, is a key
      upstream kinase of adenine monophosphate-activated protein kinase, which is a
      kinase involved in controlling cell polarity and maintaining cellular energy
      homeostasis. LKB1 is mutated in a significant number of Peutz-Jeghers syndrome
      (PJS) cases and sporadic cancers, and is most frequently mutated in lung
      adenocarcinomas; however, little is known about how LKB1 is involved in lung
      cancer progression. In this study, immunoprecipitation-HPLC tandem mass
      spectrometry (IP-LC-MS/MS) was performed to identify novel proteins interacting
      with LKB1 in lung cancer. Interestingly, many LKB1-interacting proteins acquired
      from the LC-MS/MS approach were mapped, using MetaCore pathway analysis, to the
      cystic fibrosis transmembrane conductance regulator activation pathway. Moreover,
      it was determined that LKB1 directly interacts with APC, and this LKB1-APC
      interaction was further confirmed by reverse immunoprecipitation assays, but
      GSK3beta was dispensable for the association of LKB1 and APC. Importantly, LKB1
      binds to APC to suppress the Wnt/beta-catenin signaling pathway, which is known
      to be involved in cell proliferation and migration. Subsequent analysis of the
      downstream targets of the Wnt/TCF pathway led to the identification of several
      Wnt-regulated genes, such as CD44, COX-2, survivin, and c-Myc, whose expression
      levels are downregulated by LKB1. In summary, these results demonstrate that LKB1
      regulates the Wnt pathway through a direct interaction with APC to suppress the
      tumorigenic/metastatic potential of lung tumors. IMPLICATIONS: LKB1 status
      influences the molecular circuitry (Wnt/beta-catenin pathway), cellular biology,
      and may serve as a potential therapeutic node in genetically defined subsets of
      lung cancer.

PMID- 24448688
TI  - Human papillomaviruses in anogenital epithelial lesions.

PMID- 24448690
TI  - Toe-out angle changes after total knee arthroplasty in patients with varus knee
      osteoarthritis.
AB  - PURPOSE: Toeing-out is a commonly proposed kinematic variable that has been
      suggested to reduce external knee adduction moment. Analyses of the toe-out angle
      after total knee arthroplasty (TKA) are useful for obtaining a proper
      understanding of the abnormal gait caused by varus knee osteoarthritis (OA), as
      well as performing rehabilitation after arthroplasty. Changes in the toe-out
      angle after arthroplasty have not yet been defined or analysed. METHODS: The
      study population consisted of 32 knees in 32 patients with varus knee OA who
      underwent TKA. The femorotibial angle was evaluated on standing anteroposterior
      radiographs before and after arthroplasty. The subjects underwent three
      dimensional motion capture analyses to measure gait parameters (walking speed,
      cadence, stride length, step length, step width and the relative length of the
      single-limb support (SLS) percentage of one gait cycle) and the maximal hip
      adduction angle in the stance phase, the trunk lean angle in the coronal plane
      and the toe-out angle before and 4 weeks after arthroplasty. RESULTS: The
      femorotibial angle on the side of arthroplasty improved after surgery. Among the
      measured gait parameters, only the SLS percentage increased significantly. The
      hip adduction angle and toe-out angle on the side of arthroplasty increased
      significantly after surgery. CONCLUSIONS: The knee alignment and hip adduction
      angle in the coronal plane and SLS phase were normalized after arthroplasty. The
      increase in the toe-out angle after arthroplasty may be attributable to the
      restoration of a normal knee alignment. These findings contribute to obtaining a
      proper understanding of the abnormal gait caused by varus knee OA and are useful
      for orthopaedic surgeons and rehabilitation therapists when treating patients
      after arthroplasty. LEVEL OF EVIDENCE: Prospective study, Level II.

PMID- 24448691
TI  - The hydration of serine: multipole moments versus point charges.
AB  - Next-generation force fields must incorporate improved electrostatic potentials
      in order to increase the reliability of their predictions. A crucial decision
      toward this goal is to abandon point charges in favour of multipole moments
      centered on nuclear sites. Here we compare the geometries generated by quantum
      topological multipole moments with those generated by four popular point charge
      models (TAFF, OPLS-AA, MMFF94x and PFROSST) for a hydrated serine. A main feature
      of this study is the dual comparison made, both at static level (geometry
      optimisation via energy minimisation) and at dynamic level (via molecular
      dynamics and radial/spatial distribution function analysis). At static level,
      multipolar electrostatics best reproduces the ab initio reference geometry. At
      dynamic level, multipolar electrostatics produces more structure than point
      charge electrostatics does, over the whole range. From our previous work on
      liquid water [Int. J. Quantum. Chem., 2004, 99, 685], where agreement with
      experiment only occurs when using multipole moments, we deduce that our
      predictions for hydrated serine will also be closer to experiment when using
      multipolar electrostatics. The spatial distribution function shows that only
      multipolar electrostatics shows pronounced structure at long range. Even at short
      range there are many regions where waters appear in the system governed by
      multipolar electrostatics but not in that governed by point charges. 

PMID- 24448689
TI  - A meta-analysis of minimally invasive and conventional medial parapatella
      approaches for primary total knee arthroplasty.
AB  - PURPOSE: Minimally invasive surgical (MIS) approaches for total knee arthroplasty
      (TKA) have become increasingly popular for doctors and patients. They have argued
      that it decreases post-operative pain, accelerates functional recovery and
      increases patient satisfaction due to less injury. However, critics are concerned
      about TKA's possible effects on component position and with complications,
      considering the procedure's limited exposure. The purpose of this study was to
      summarise the best evidence in comparing the clinical and radiological outcomes
      between MIS and a conventional approach in TKA. METHODS: Electronic databases
      were systematically searched to identify relevant randomised controlled trials
      (RCTs). Our search strategy followed the requirements of the Cochrane Library
      Handbook. Methodological quality was assessed, and data were extracted
      independently by two authors. RESULTS: Thirty studies, including 2,536 TKAs, were
      reviewed: 1,259 minimally invasive and 1,277 conventional exposure TKAs. The
      results showed that while the MIS group had longer operation times and tourniquet
      times, it had superior outcomes in KSS (objective and total), range of motion,
      flexion range of motion, flexion 90 degrees  day, straight leg-raising day, total
      blood loss and decrease in haemoglobin. However, wound-healing problems occurred
      more frequently in the MIS group. There were no statistically significant
      differences in other clinical or radiological outcomes between the MIS and
      conventional groups in TKA. CONCLUSION: The preliminary results indicate that the
      MIS approach provides an alternative to the conventional approach, with earlier
      rehabilitation but no malpositioning or severe complications. Wound-healing
      problems can be treated easily and effectively, and the risk also decreases as
      surgeons become more experienced, and more user-friendly instruments are
      invented. Potential benefits in medium- and long-term outcomes require larger,
      multicentre and well-conducted RCTs to confirm. LEVEL OF EVIDENCE: Therapeutic
      study, Level II.

PMID- 24448693
TI  - Gas diffusion as a new fluidic unit operation for centrifugal microfluidic
      platforms.
AB  - A centrifugal microfluidic platform prototype with an integrated membrane for gas
      diffusion is presented for the first time. The centrifugal platform allows
      multiple and parallel analysis on a single disk and integrates at least ten
      independent microfluidic subunits, which allow both calibration and sample
      determination. It is constructed with a polymeric substrate material and it is
      designed to perform colorimetric determinations by the use of a simple
      miniaturized optical detection system. The determination of three different
      analytes, sulfur dioxide, nitrite and carbon dioxide, is carried out as a proof
      of concept of a versatile microfluidic system for the determination of analytes
      which involve a gas diffusion separation step during the analytical procedure. 

PMID- 24448692
TI  - Effects of topiroxostat on the serum urate levels and urinary albumin excretion
      in hyperuricemic stage 3 chronic kidney disease patients with or without gout.
AB  - BACKGROUND: Topiroxostat, a selective xanthine oxidase inhibitor, shows effective
      reduction in the serum urate level in hyperuricemic patients with or without
      gout. The objective of this study was to evaluate the efficacy and safety of
      topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or
      without gout. METHODS: The study design was a 22-week, randomized, multicenter,
      double-blind study. The enrolled patients were randomly assigned to treatment
      with topiroxostat 160 mg/day (n = 62) or to the placebo (n = 61). The endpoints
      were the percent change in the serum urate level, change in the estimated
      glomerular filtration rate, the urinary albumin-to-creatinine ratio, the
      proportion of patients with serum urate levels of 356.88 MUmol/L or less, blood
      pressure, and serum adiponectin. RESULTS: After 22 weeks, although the changes in
      the estimated glomerular filtration rate and blood pressure were not significant,
      the percent change in the serum urate level (-45.38 vs. -0.08 %, P < 0.0001) and
      the percent change in urinary albumin-to-creatinine ratio (-33.0 vs. -6.0 %, P =
      0.0092) were found to have decreased in the topiroxostat as compared with the
      placebo. Although the incidence of 'alanine aminotransferase increased' was
      higher in the topiroxostat, serious adverse event rates were similar in the two
      groups. CONCLUSION: Topiroxostat 160 mg effectively reduced the serum urate level
      in the hyperuricemic stage 3 chronic kidney disease patients with or without
      gout.

PMID- 24448694
TI  - Charging Australians to see a family doctor would make them "think twice," says
      think tank.

PMID- 24448695
TI  - The global slowdown effect: why does perceptual grouping reduce perceived speed?
AB  - The percept of four rotating dot pairs is bistable. The "local percept" is of
      four pairs of dots rotating independently. The "global percept" is of two large
      squares translating over one another (Anstis & Kim 2011). We have previously
      demonstrated (Kohler, Caplovitz, & Tse 2009) that the global percept appears to
      move more slowly than the local percept. Here, we investigate and rule out
      several hypotheses for why this may be the case. First, we demonstrate that the
      global slowdown effect does not occur because the global percept is of larger
      objects than the local percept. Second, we show that the global slowdown effect
      is not related to rotation-specific detectors that may be more active in the
      local than in the global percept. Third, we find that the effect is also not due
      to a reduction of image elements during grouping and can occur with a stimulus
      very different from the one used previously. This suggests that the effect may
      reflect a general property of perceptual grouping. Having ruled out these
      possibilities, we suggest that the global slowdown effect may arise from emergent
      motion signals that are generated by the moving dots, which are interpreted as
      the ends of "barbell bars" in the local percept or the corners of the illusory
      squares in the global percept. Alternatively, the effect could be the result of
      noisy sources of motion information that arise from perceptual grouping that, in
      turn, increase the influence of Bayesian priors toward slow motion (Weiss,
      Simoncelli, & Adelson 2002). 

PMID- 24448696
TI  - An objective measure of auditory stream segregation based on molecular
      psychophysics.
AB  - Auditory stream segregation is an important paradigm in the study of auditory
      scene analysis. Performance-based measures of auditory stream segregation have
      received increasing use as a complement to subjective reports of streaming. For
      example, the sensitivity in discriminating a temporal shift imposed on one B tone
      in an ABA sequence consisting of A and B tones that differ in frequency is often
      used to infer the perceptual organization (one stream vs. two streams).
      Limitations of these measures are discussed here, and an alternative measure
      based on the combination of decision weights and sensitivity is suggested. In the
      experiment, for ABA and ABB sequences varying in tempo (fast/slow) and duration
      (long/short), the sensitivity (d') in the temporal shift discrimination task did
      not differ between fast and slow sequences, despite strong differences in
      perceptual organization. The decision weights assigned to within-stream and
      between-stream interonset intervals also deviated from the idealized pattern of
      near-exclusive reliance on between-stream information in the subjectively
      integrated case, and on within-stream information in the subjectively segregated
      case. However, an estimate of internal noise computed using a combination of the
      estimated decision weights and sensitivity differentiated between sequences that
      were predominantly perceived as integrated or segregated, with significantly
      higher internal noise estimates for the segregated case. Therefore, the method of
      using a combination of decision weights and sensitivity provides a measure of
      auditory stream segregation that overcomes some of the limitations of purely
      sensitivity-based measures. 

PMID- 24448697
TI  - Contextual integration of visual objects necessitates attention.
AB  - Objects that form a contextually coherent percept are grasped more rapidly and
      efficiently than objects that are contextually inconsistent with each other. The
      extent to which such clustering processes depend on visual attention is largely
      unknown. The present research examined the necessity of attention for object-to
      object contextual integration processes during a brief visual glimpse.
      Participants performed an object classification task on associated object pairs
      that were presented for a short duration (59 ms). Objects were positioned either
      in expected relative locations (e.g., a desk lamp on a desk) or in unexpected
      relative locations (e.g., a desk lamp under a desk). When both stimuli were
      relevant to task requirements, latencies to spatially consistent object pairs
      were significantly shorter than those to spatially inconsistent pairs (Experiment
      1). These contextual effects disappeared, however, when spatial attention was
      drawn to one of the two object stimuli while its counterpart object appeared
      outside the main focus of attention, serving as a task-irrelevant distractor
      (Experiment 2). Attentional modulation of contextual integration processes was
      shown to be independent of distractor recognition per se (Experiment 3). Finally,
      the role of goal-directed (endogenous) and spatial (exogenous) attention factors
      in contextual integration was explored (Experiment 4). Taken together, our
      findings suggest that contextual associations play an important role in
      processing multiple-object visual displays. However, regardless of whether
      objects are associated by active or passive relations, the construction of a
      coherent contextual representation strongly relies on the availability of
      attentional capacity. Possible implications for theories of scene and object
      recognition are discussed. 

PMID- 24448698
TI  - Clinicopathological profile of female Sudanese patients with locally advanced
      breast cancer.
AB  - BACKGROUND: In Sudan, breast cancer is one of the most common malignancy
      affecting women and the incidence rates appear to be rising. Unfortunately, most
      of the patients presented in advanced stage. OBJECTIVE: To obtain information on
      demographic characteristics, clinicopathological profile and factors related to
      late presentation. MATERIALS AND METHODS: Descriptive study. 144 patients who
      presented from April 2009 through May 2011 with locally advanced breast cancer
      were included in this study. RESULTS: 144 patients ranging in age from 25-71
      years (mean 47 years) were included in the study. Of these 62.5% were
      premenopausal women. More than 60% of the patients presented after > 1 year
      following onset of symptoms. 68% of patients attributed their late presentation
      for lack of education and financial aspects. CONCLUSION: Our study shows that
      locally advanced breast cancer patients presented at a younger age. Lack of
      education, financial issues and dependency on traditional medicine are
      encountered for this late presentation. We suggest that the attitude of Sudanese
      females towards breast cancer has to change through continuous but targeted
      public education.

PMID- 24448699
TI  - Functional responses of the rough-legged buzzard in a multi-prey system.
AB  - The functional response is a key element of predator-prey interactions. Basic
      functional response theory explains foraging behavior of individual predators,
      but many empirical studies of free-ranging predators have estimated functional
      responses by using population-averaged data. We used a novel approach to
      investigate functional responses of an avian predator (the rough legged-buzzard
      Buteo lagopus Pontoppidan, 1763) to intra-annual spatial variation in rodent
      density in subarctic Sweden, using breeding pairs as the sampling unit. The rough
      legged buzzards responded functionally to Norwegian lemmings (Lemmus lemmus L.
      1758), grey-sided voles (Myodes rufocanus Sundevall, 1846) and field voles
      (Microtus agrestis L. 1761), but different rodent prey were not utilised
      according to relative abundance. The functional response to Norwegian lemmings
      was a steep type II curve and a more shallow type III response to grey-sided
      voles. The different shapes of these two functional responses were likely due to
      combined effects of differences between lemmings and grey-sided voles in habitat
      utilisation, anti-predator behaviour and size-dependent vulnerability to
      predation. Diet composition changed less than changes in relative prey abundance,
      indicating negative switching, with high disproportional use of especially
      lemmings at low relative densities. Our results suggest that lemmings and voles
      should be treated separately in future empirical and theoretical studies in order
      to better understand the role of predation in this study system. 

PMID- 24448700
TI  - Sequential effects of root and foliar herbivory on aboveground and belowground
      induced plant defense responses and insect performance.
AB  - Plants are often simultaneously or sequentially attacked by multiple herbivores
      and changes in host plants induced by one herbivore can influence the performance
      of other herbivores. We examined how sequential feeding on the plant Plantago
      lanceolata by the aboveground herbivore Spodoptera exigua and the belowground
      herbivore Agriotes lineatus influences plant defense and the performance of both
      insects. Belowground herbivory caused a reduction in the food consumption by the
      aboveground herbivore independent of whether it was initiated before, at the same
      time, or after that of the aboveground herbivore. By contrast, aboveground
      herbivory did not significantly affect belowground herbivore performance, but
      significantly reduced the performance of later arriving aboveground conspecifics.
      Interestingly, belowground herbivores negated negative effects of aboveground
      herbivores on consumption efficiency of their later arriving conspecifics, but
      only if the belowground herbivores were introduced simultaneously with the early
      arriving aboveground herbivores. Aboveground-belowground interactions could only
      partly be explained by induced changes in an important class of defense
      compounds, iridoid glycosides (IGs). Belowground herbivory caused a reduction in
      IGs in roots without affecting shoot levels, while aboveground herbivory
      increased IG levels in roots in the short term (4 days) but only in the shoots in
      the longer term (17 days). We conclude that the sequence of aboveground and
      belowground herbivory is important in interactions between aboveground and
      belowground herbivores and that knowledge on the timing of exposure is essential
      to predict outcomes of aboveground-belowground interactions.

PMID- 24448701
TI  - Images in vascular medicine. Asymptomatic aortic coarctation diagnosed because of
      a vast calcified collateral circulation.

PMID- 24448702
TI  - The diagnosis of thoracic malignant mesothelioma: practical considerations and
      recent developments.
AB  - Pleural biopsies for the evaluation of malignant mesothelioma can be some of the
      most challenging cases faced by the practicing surgical pathologist. We review
      the epidemiology, clinical presentation, and imaging studies in patients with
      malignant mesothelioma, and then present a practical approach to the diagnosis
      using the cytologic features for malignancy and whether there is an epithelioid
      or spindled morphology; four main scenarios are discussed. The pertinent
      immunohistochemical work-up is reviewed for each scenario. Following this general
      overview, more unusual histologic patterns are compared and unusual presentations
      are discussed. Brief mention of grading systems for malignant mesothelioma and
      the use of electron microscopy and molecular studies is made. Practical
      considerations in the diagnosis of malignant mesothelioma are made throughout. 

PMID- 24448703
TI  - Well-differentiated pediatric glial neoplasms with features of oligodendroglioma,
      angiocentric glioma and dysembryoplastic neuroepithelial tumors: a morphological
      diagnostic challenge.
AB  - OBJECTIVE: Oligodendrogliomas are rare in the pediatric population, and most
      oligodendroglioma-like tumors in this age group may belong to other entities. In
      addition, accurate diagnosis and grading of such lesions using criteria developed
      for adult oligodendrogliomas prove difficult, and often controversial. MATERIAL
      AND METHOD: During a study of tumors previously diagnosed as pediatric
      oligodendroglioma, we identified four tumors displayed features of that resembled
      oligodendroglioma, angiocentric glioma and dysembryoplastic neuroepithelial tumor
      but could not be classified as either one of these entities. Ther clinical,
      histological and immunohistochemical features of these cases were investigated in
      this study. RESULTS: Two male (both 9 years old) and two female (ages 4 years and
      20 months) patients presented with new onset of seizures. All patients were
      treated surgically, and two required reoperation. Histologically, the tumors were
      well-differentiated glial neoplasms with focal angiocentric pattern, delicate
      vascularity, diffuse growth, infiltrative margins, cortical nodules, focal myxoid
      areas, and leptomeningeal extension. Immunohistochemical studies showed diffuse
      nuclear positivity with Olig-2 and GFAP antibodies, whereas staining with
      neuronal markers, EMA, p53, and IDH1 were negative. Fluorescent in-situ
      hybridization analysis demonstrated intact 1p/19q in all tumors, and there was no
      ultrastructural evidence of ependymal differentiation. All patients were alive
      with disease with a mean follow-up of 112 months. CONCLUSION: These four cases
      illustrate the morphological diversity of well-differentiated, oligodendroglioma
      like glial neoplasms and the uncertainty in their classification among pediatric
      tumors.

PMID- 24448704
TI  - Correlation of survivin and MMP9 expressions with prognosis and
      clinicopathological parameters in surface epithelial ovarian carcinomas.
AB  - OBJECTIVE: Pathological stage is the most important prognostic factor in ovarian
      carcinomas, and many studies have been carried out to predict prognosis. In our
      study, we searched the expression of survivin, which prevents apoptosis and
      matrix metalloproteinase-9 (MMP-9), which promotes the metastasis of the tumour
      by splitting up the basal membrane in primary epithelial ovarian carcinomas. We
      aimed to observe their effects on prognosis by comparing clinicopathological
      parameters. MATERIAL AND METHOD: 60 cases diagnosed with epithelial ovarian
      carcinoma between 2003 and 2008 and treated and followed up at the oncology
      clinic were included in the study. 42 patients were serous, 11 endometrioid, 5
      mixed type, 1 was clear cell and 1 was undifferentiated adenocarcinoma. Survivin
      and MMP-9 expression was evaluated in each tumour and assosication with
      clinicopathological parameters (age, tumour diameter, localisation, histological
      type of tumour, grade, stage, recurrence and metastasis) were searched and also
      overall survival and disease free of survival were evaluated. RESULTS: Survivin
      was statistically insignificant within the clinicopathological parameters. The
      correlation between the tumour grade and the staining density of MMP-9 in
      epithelial cells (p=0.028) and the correlation between disease free of survival
      and MMP-9 expression in stromal cells (p=0.0326) was significant. When the stage
      was compered with clinocopathologic parameters; recurrence (p=0.005) and death
      rates (p < 0.001) were significantly increased but overall survival (p=0.0269)
      was significantly decreased in advanced-stage patients. CONCLUSION: In the
      present study, the stage was found to be an important prognostic parameter in
      surface epithelial ovarian carcinomas and an association was found between MMP-9
      stromal staining and survival.

PMID- 24448705
TI  - Comparison of cervical cytological screening results between postmenopausal and
      elderly women.
AB  - OBJECTIVE: There is insufficient data on geriatric period cervical cytology
      screening in our country. The aim of this study was to compare the cervical
      cytological results among elderly women and women aged between 45-64 years.
      MATERIAL AND METHOD: A comparison of cervical cytological results of 273 women
      aged over 65 years and 388 women aged between 45-64 years from January 2010 to
      June 2013 was performed for presence of cytological abnormalities. Adequacy was
      assessed according to the criteria of the 2001 Bethesda System. Cervical
      cytological abnormalities were classified as follows: atypical squamous cell of
      undetermined significance (ASCUS), cannot exclude a high-grade squamous
      intraepithelial lesion (ASC-H), low grade squamous intraepithelial lesion (LSIL),
      high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma
      (SSC). RESULTS: Overall, the prevalence of cytological abnormality was 3% and the
      prevalence of ASCUS, ASCH, LSIL, and HSIL was 1.8%, 0.3%, 0.6% and 0.3%,
      respectively. Cytological abnormalities were detected to be higher in the
      geriatric group in comparison to the postmenopausal group (%5.1 vs. %1.5)
      (p=0.008). ASCUS was detected to be 3.7% in the geriatric group and 0.5% in the
      postmenopausal group (p=0.005). There was no statistically significant difference
      between the groups in means of other cytological anomalies. The reactive
      inflammatory changes were detected more in the postmenopausal group and atrophic
      changes in the geriatric group (p < 0.001). CONCLUSION: It should not be
      forgotten that although the cervical screening follow-up program is discontinued
      in elderly women, squamous intraepithelial lesions can still be encountered in
      this group even if the rate is low.

PMID- 24448706
TI  - Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial
      sarcoma.
AB  - OBJECTIVE: We aimed to determine the prognostic value of bcl-2, c-myc and
      survivin in synovial sarcoma cases and to evaluate the relationship between the
      conventional morphological findings with prognosis. MATERIAL AND METHOD: In this
      study, we evaluated 81 synovial sarcoma cases referred to our tertiary tumor
      center during a period of 20 years. We applied bcl-2, c-myc and survivin
      immunohistochemically and investigated the relationship with prognosis for those
      65 cases with follow-up. The relationship between the conventional morphological
      findings (mitosis, necrosis, grade) with prognosis was also investigated.
      RESULTS: Five-year disease free survival rate was 44% and ten-year progression
      free survival rate was 38%, reflecting the aggressive behavior of synovial
      sarcoma. Tumor grade (according to FNCLCC) was the most significant prognostic
      input in this study. We obtained a significant difference between grade II (40
      cases) and grade III (24 cases) group regarding progression-free survival and
      overall survival (p < 0.001 and p < 0.001 respectively). Grade II was divided
      into two groups according to mitotic index and necrosis (grade IIa and IIb) and
      there was a significant difference between them regarding prognosis (p=0.013 for
      progression free survival, p=0.003 for overall survival). There was a significant
      relationship between bcl-2 negative plus focally weak positive cases (9 cases)
      and focally strong cases (21 cases) and diffuse strong cases (35 cases) (p=0.042
      and p=0.016 respectively). There was a significant relation between c-myc
      negative cases (25 cases) and nuclear positive cases (17 cases) regarding overall
      survival (p=0.043) and between c-myc negative cases and cytoplasmic positive
      cases (23 cases) regarding progression free survival (p=0.05). The relation
      between survivin and prognosis was not significant. CONCLUSION: Tumor grade was
      the most significant prognostic parameter in this study. The grade IIa group
      (with less than 10 mitoses in 10 HPF, without necrosis) had a better prognosis
      than both the grade IIb and III groups. The grade IIb group was closer to grade
      III regarding the prognosis. Bcl-2 and c-myc (nuclear and/or cytoplasmic)
      immunohistochemical positivity had prognostic value but this finding has to be
      confirmed by large series.

PMID- 24448707
TI  - Malignant pilomatricoma: two new observations and review of the relevant
      literature.
AB  - Malignant pilomatricoma or pilomatrical carcinoma is a rare malignant hair
      follicle neoplasm. This tumor is locally aggressive with increased tendency to
      recur, but a low metastatic potential. Its histopathological diagnosis is
      difficult and based on a detailed evaluation of the infiltrative nature, the
      importance of the mummified and necrotic cell component, atypical mitoses, and
      perineural or vascular invasion. Surgical wide resection is the recommended
      treatment. It reduces the risk of focal recurrence by 50%. Here we report two new
      cases including one that occurred on a lesion initially diagnosed as benign
      pilomatricoma. 

PMID- 24448708
TI  - A giant primary sclerosing lipogranuloma of the scrotum.
AB  - Sclerosing lipogranuloma is a rare, benign disease that can affect several
      organs, particularly of genitourinary system in males. The majority of the cases
      are secondary to exogenous foreign bodies. The masses are composed of
      granulomatous tissue formed around an either exogenous or endogenous lipomatous
      substance. We describe a 47-year-old male patient who presented with a growing,
      painless scrotal mass on physical examination. The mass was in 20 cm diameter and
      the laboratory findings were in normal limits. Pathologic evaluation confirmed
      the diagnosis of scrotal sclerosing lipogranuloma. To the best of our knowledge,
      this is the biggest scrotal sclerosing lipogranuloma case in the literature. We
      aimed with this presentation to keep in mind this benign lesion and also to
      assist the algorithmic approach. 

PMID- 24448709
TI  - Analysis of high risk HPV subtypes associated with cervical intraepithelial
      neoplasia: a single centre retrospective study in the Mediterranean region of
      Turkey.

PMID- 24448710
TI  - Atypical teratoid rhabdoid tumor in childhood, 15 cases of a single institute
      experience.
AB  - OBJECTIVE: Atypical teratoid rhabdoid tumor is a rare neoplasm with a distinct
      cytogenetic profile that predominates in infancy. Many cases show predominance of
      small cells with scanty rhabdoid cells, making recognition of this tumor
      difficult. We aim at describing our experience with atypical teratoid rhabdoid
      tumor cases diagnosed over a 6-year period. MATERIAL AND METHOD:
      Clinicopathologic features and immunohistochemical staining of atypical teratoid
      rhabdoid tumor cases diagnosed between 2006 and 2011 are presented. RESULTS:
      Fifteen cases were identified including 9 males with a median age of 26 months.
      The most common presenting symptom was recurrent vomiting with a mean duration of
      6 weeks. Nine cases (60%) were infratentorial and cerebrospinal fluid was
      positive in 2 cases (13.3%) at time of diagnosis. The median overall survival of
      the group was 9.5 months. All cases except one showed admixture of rhabdoid
      and/or small round blue cells in variable proportions. Only 5 out of fourteen
      referred cases (35.7%) were correctly diagnosed. Three cases showed unusual
      growth patterns. In 2 cases, nodular medulloblastoma-like growth pattern
      predominated, with loss of INI-1/BAF47 staining both within the nodules and the
      inter-nodular areas. The third case contained scattered individual and small
      groups of large cells with abundant acidophilic cytoplasm and eccentric nuclei,
      reminiscent of rhabdomyoblasts that were positive for GFAP and desmin, and
      retained nuclear staining for INI-1/BAF47, consistent with reactive gemistocytes.
      CONCLUSION: Pathologists should be aware of the various, and unusual
      histopathologic patterns of atypical teratoid rhabdoid tumor. INI-1/ BAF47
      immunostain should be performed on all central nervous system embryonal tumors,
      especially in infants and young children.

PMID- 24448711
TI  - Comparison of Nigella sativa- and exercise-induced models of cardiac hypertrophy:
      structural and electrophysiological features.
AB  - Exercise training is employed as supplementary therapeutic intervention for heart
      failure, due to its ability to induce physiological cardiac hypertrophy. In
      parallel, supplementation with Nigella sativa (N. sativa) was found to enhance
      myocardial function and induce cardiac hypertrophy. In this study, we aim to
      compare the morphological and electrophysiological changes associated with these
      patterns of cardiac hypertrophy and the possible changes upon administration of
      N. sativa to exercise-trained animals. Fifty-six adult Wistar rats were divided
      into: control, Nigella-treated (N), exercise-trained (E), and Nigella-treated
      exercise-trained (NE) rats. Daily 800 mg/kg N. sativa was administered orally to
      N and NE. E and NE ran on treadmill, 2 h/day. At the end of 8 weeks ECG, body
      weight (BW), heart weight (HW), and left ventricular weight (LVW) were recorded.
      Hematoxylin and Eosin and periodic acid-Schiff sections were prepared to study
      the histology of left ventricles and to measure diameter of cardiomyocytes
      (Cdia). HW/BW, LVW/BW, and mean Cdia were significantly higher in all
      experimental animals compared to the controls. Histology showed normal
      cardiomyocytes with no fibrosis. ECG showed significantly lower heart rates,
      higher QRS amplitude, and ventricular specific potential in NE group compared to
      control group. Supplementation of N. sativa demonstrated a synergistic effect
      with exercise training as Nigella-exercise-induced cardiac hypertrophy had lower
      heart rate and well-matched electrical activity of the heart to its mass.
      Therefore, this model of cardiac hypertrophy might be introduced as a new
      therapeutic strategy for treatment for heart failure with superior advantages to
      exercise training. 

PMID- 24448712
TI  - Cardioprotective effect of mumie (shilajit) on experimentally induced myocardial
      injury.
AB  - This study assessed the effects of mumie (shilajit) pre-treatment, a traditional
      drug which is well known in the ancient medicine of both east and west, on
      cardiac performance of rats subjected to myocardial injury. Animals were divided
      into control, M250, and M500 (received mumie at dosages of 250 and 500 mg/kg/day,
      orally for 7 days, respectively) main groups each consisting of two subgroups
      with and without heart injury. On the 6th and 7th days, isoproterenol (ISO) (85
      mg/kg i.p.) was injected (s.c.) to half of the animal subgroups to induce
      myocardial damage. On the 8th day, after hemodynamic parameter recordings, hearts
      were removed for further evaluation. Mumie pre-treatment had no significant
      effects on hemodynamic and cardiac indices of normal animals. When the cardiac
      injury was induced, mumie maintained the +/-dp/dt maximum, attenuated the serum
      cardiac troponin I, and reduced the severity of cardiac lesions. Despite the mild
      positive effects of mumie on total antioxidant capacity and lipid proxidation
      index, no significant difference was observed among animal groups. The findings
      suggest the prominent cardioprotective effect of mumie against destructive
      effects of ISO. It seems that other mechanisms than reinforcements of antioxidant
      system are involved in this beneficial effect. 

PMID- 24448713
TI  - Microvascular dysfunction with increased vascular leakage response in mice
      systemically exposed to arsenic.
AB  - The mechanisms underlying cardiovascular disease induced by arsenic exposure are
      not completely understood. The objectives of this study were to investigate
      whether arsenic-fed mice have an increased vascular leakage response to
      vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity
      is involved in mustard oil-induced leakage. ICR mice were fed water or sodium
      arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents
      was quantified using the Evans blue (EB) technique or vascular labeling with
      carbon particles. Increased EB leakage and high density of carbon-labeled
      microvessels were detected in arsenic-fed mice treated with mustard oil.
      Histamine induced significantly higher vascular leakage in arsenic-fed mice than
      in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the
      neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil
      induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and
      NK1R were similar in both groups. PP2A activity was significantly higher in the
      arsenic-fed mice compared with the control group. These findings indicate that
      microvessels generally respond to vasoactive agents, and that the increased PP2A
      activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice.
      Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in
      response to vasoactive agents. 

PMID- 24448714
TI  - Systemic and characteristic metabolites in the serum of streptozotocin-induced
      diabetic rats at different stages as revealed by a (1)H-NMR based metabonomic
      approach.
AB  - Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by
      abnormal metabolism of carbohydrates, lipids, and proteins. Investigating the
      changes in metabolic pathways during the evolution of diabetes mellitus may
      contribute to the understanding of its metabolic features and pathogenesis. In
      this study, serum samples were collected from diabetic rats and age-matched
      controls at different time points: 1 and 9 weeks after streptozotocin (STZ)
      treatment. (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with
      quantitative analysis was performed to study the metabolic changes. The serum
      samples were also subjected to clinical chemistry analysis to verify the
      metabolic changes observed by metabonomics. Partial least squares discriminant
      analysis (PLS-DA) demonstrated that the levels of serum metabolites in diabetic
      rats are different from those in control rats. These findings indicate that the
      metabolic characteristics of the two groups are markedly different at 1 and 9
      weeks. Quantitative analysis showed that the levels of some metabolites, such as
      pyruvate, lactate, citrate, acetone, acetoacetate, acetate, glycerol, and valine,
      varied in a time-dependent manner in diabetic rats. These results suggest that
      serum metabolites related to glycolysis, the tricarboxylic acid cycle,
      gluconeogenesis, fatty acid beta-oxidation, branched-chain amino acid metabolism,
      and the tyrosine metabolic pathways are involved in the evolution of diabetes.
      The metabolic changes represent potential features and promote a better
      understanding of the mechanisms involved in the development of diabetes mellitus.
      This work further suggests that (1)H NMR metabonomics is a valuable approach for
      providing novel insights into the pathogenesis of diabetes mellitus and its
      complications. 

PMID- 24448716
TI  - Effects of hydrogen bonding interactions on the redox potential and molecular
      vibrations of plastoquinone as studied using density functional theory
      calculations.
AB  - The effects of H-bonding on the redox potential and molecular vibrations of
      plastoquinone (PQ) that functions as a primary and a secondary quinone electron
      acceptor (QA and QB, respectively) in photosystem II (PSII) in plants and
      cyanobacteria were investigated using density functional theory calculations.
      Calculations were performed on the neutral and semiquinone anion forms of PQ and
      its H-bonded complexes, which form H-bonds with water molecules, or using amino
      acid models mimicking the interactions of QA and QB. The calculated redox
      potential (E(o)) of PQ showed a linear relationship with the number of H-bonds,
      and the E(o) increased by +100-200 mV with the addition of one H-bond.
      Vibrational analysis of the model PQ complexes showed that the CO stretching
      vibrations of neutral PQ are sensitive to the number and symmetry of H-bonding
      interactions, providing criteria to determine the H-bonding structure. Although
      no specific trend in the H-bonding dependency was found for anionic PQ, complex
      spectral features in the CO stretching region due to significant couplings with
      other PQ vibrations and the vibrations of H-bonding amino acids are useful
      monitors of the change in the H-bonding structure of anionic PQ in proteins. The
      calculated E(o) values and infrared spectra of the QA and QB models are
      consistent with the view that one additional H-bond to QB from D1-Ser264 largely
      contributes to the redox potential gap between QA and QB in PSII. 

PMID- 24448715
TI  - Ept7 influences estrogen action in the pituitary gland and body weight of rats.
AB  - Estrogens control many aspects of pituitary gland biology, including regulation
      of lactotroph homeostasis and synthesis and secretion of prolactin. In rat
      models, these actions are strain specific and heritable, and multiple
      quantitative trait loci (QTL) have been mapped that impact the responsiveness of
      the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female
      progeny generated in an intercross between BN rats, in which the lactotroph
      population is insensitive to estrogens, and ACI rats, which develop lactotroph
      hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen
      treatment. The primary objective of this study was to confirm the existence of
      Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary
      gland of female and male rats to 17beta-estradiol (E2) and diethylstilbestrol
      (DES), respectively. Secondary objectives were to determine if Ept7 influences
      the responsiveness of the male reproductive tract to DES and to identify other
      discernible phenotypes influenced by Ept7. To achieve these objectives, a
      congenic rat strain that harbors BN alleles across the Ept7 interval on the
      genetic background of the ACI strain was generated and characterized to define
      the effect of administered estrogens on the anterior pituitary gland and male
      reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect
      on development of lactotroph hyperplasia in response to estrogen treatment, but
      does not affect atrophy of the male reproductive tissues in response to hormone
      treatment. Ept7 was also observed to exert gender specific effects on body weight
      in young adult rats. 

PMID- 24448717
TI  - Immunocytochemical and ultrastructural identification of adenohypophyseal cells
      in Ctenopharyngodon idella (Cypriniformes: Cyprinidae) during gonadal
      differentiation.
AB  - The adenohypophysis was studied by immunocytochemical and ultrastructural methods
      in juvenile grass carp (Ctenopharyngodon idella) from natural reproduction in
      Northern Italian rivers. The adenohypophysis included the rostral pars distalis
      (RPD), the proximal pars distalis (PPD) and the pars intermedia (PI), all deeply
      penetrated by branches of the neurohypophysis (Nh). The prolactin (PRL),
      adrenocorticotropic (ACTH), somatotropic (GH), thyrotropic (TSH), gonadotropic
      type I (GtH I) and type II (GtH II), somatolactin (SL), melanotropic (MSH) and
      endorphin (END) cells were identified with antisera raised against piscine and
      human pituitary hormones. In juveniles of 51-69 mm of total body length (TL) with
      undifferentiated gonads, the PRL cells, arranged in thick strands, occupied most
      of the RPD. The ACTH and GH cells organized in cords bordering Nh were,
      respectively, confined to RPD and PPD. The TSH cells were scattered among ACTH
      cells in RPD and among GH cells in PPD. Cells simultaneously immunoreactive to
      anti-follicle stimulating hormone and to anti-croaker gonadotropin were
      intermingled among GH and TSH cells, which were mostly in the dorsal PPD. The SL
      cells were detected in PI layers bordering the Nh. The MSH and END cells were
      intermingled in PI and, unlike what observed in other teleosts, their respective
      antisera did not cross-react. In individuals of 78-112 mm TL with gonads at the
      beginning of differentiation, the GtH II cells were detected in PPD; all other
      cell types increased in number. These results, supported by ultrastructural
      investigations, suggest that SL and GtH II cells are directly involved in gonadal
      differentiation in C. idella. 

PMID- 24448718
TI  - Ontogenetic development of digestive functionality in golden pompano Trachinotus
      ovatus (Linnaeus 1758).
AB  - Ontogenetic development of the digestive system in golden pompano (Trachinotus
      ovatus, Linnaeus 1758) larvae was histologically and enzymatically studied from
      hatch to 32 day post-hatch (DPH). The development of digestive system in golden
      pompano can be divided into three phases: phase I starting from hatching and
      ending at the onset of exogenous feeding; phase II starting from first feeding (3
      DPH) and finishing at the formation of gastric glands; and phase III starting
      from the appearance of gastric glands on 15 DPH and continuing onward. The
      specific activities of trypsin, amylase, and lipase increased sharply from the
      onset of first feeding to 5-7 DPH, followed by irregular fluctuations. Toward the
      end of this study, the specific activities of trypsin and amylase showed a
      declining trend, while the lipase activity remained at similar levels as it was
      at 5 DPH. The specific activity of pepsin was first detected on 15 DPH and
      increased with fish age. The dynamics of digestive enzymes corresponded to the
      structural development of the digestive system. The enzyme activities tend to be
      stable after the formation of the gastric glands in fish stomach on 15 DPH. The
      composition of digestive enzymes in larval pompano indicates that fish are able
      to digest protein, lipid and carbohydrate at early developmental stages. Weaning
      of larval pompano is recommended from 15 DPH onward. Results of the present study
      lead to a better understanding of the ontogeny of golden pompano during the
      larval stage and provide a guide to feeding and weaning of this economically
      important fish in hatcheries. 

PMID- 24448719
TI  - Primary syphilis presenting as bilateral nipple-areola eczematoid lesions.

PMID- 24448720
TI  - Enantioselective synthesis of alpha-halo-alpha-alkylmalonates via phase-transfer
      catalytic alpha-alkylation.
AB  - A new enantioselective synthetic method for alpha-halo-alpha-alkylmalonates is
      reported. alpha-Alkylation of diphenylmethyl tert-butyl alpha-halomalonates under
      phase-transfer catalytic conditions (solid KOH, toluene, -40  degrees C) in the
      presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide (5 mol%) afforded
      diphenylmethyl tert-butyl alpha-halo-alpha-alkylmalonates in very high chemical
      yields (up to 99%) and optical yields (up to 93% ee). 

PMID- 24448721
TI  - Speech perception in noise with a harmonic complex excited vocoder.
AB  - A cochlear implant (CI) presents band-pass-filtered acoustic envelope information
      by modulating current pulse train levels. Similarly, a vocoder presents envelope
      information by modulating an acoustic carrier. By studying how normal hearing
      (NH) listeners are able to understand degraded speech signals with a vocoder, the
      parameters that best simulate electric hearing and factors that might contribute
      to the NH-CI performance difference may be better understood. A vocoder with
      harmonic complex carriers (fundamental frequency, f0 = 100 Hz) was used to study
      the effect of carrier phase dispersion on speech envelopes and intelligibility.
      The starting phases of the harmonic components were randomly dispersed to varying
      degrees prior to carrier filtering and modulation. NH listeners were tested on
      recognition of a closed set of vocoded words in background noise. Two sets of
      synthesis filters simulated different amounts of current spread in CIs. Results
      showed that the speech vocoded with carriers whose starting phases were maximally
      dispersed was the most intelligible. Superior speech understanding may have been
      a result of the flattening of the dispersed-phase carrier's intrinsic temporal
      envelopes produced by the large number of interacting components in the high
      frequency channels. Cross-correlogram analyses of auditory nerve model
      simulations confirmed that randomly dispersing the carrier's component starting
      phases resulted in better neural envelope representation. However, neural metrics
      extracted from these analyses were not found to accurately predict speech
      recognition scores for all vocoded speech conditions. It is possible that central
      speech understanding mechanisms are insensitive to the envelope-fine structure
      dichotomy exploited by vocoders.

PMID- 24448722
TI  - Financial incentive of home continuous positive airway pressure machine use in
      the inpatient hospital setting.
AB  - OBJECTIVES/HYPOTHESIS: Obstructive sleep apnea (OSA) is increasingly recognized
      as a significant factor in perioperative and inpatient health. Because of this,
      hospitalized OSA patients are encouraged to utilize continuous positive airway
      pressure (CPAP) therapy while inpatients. We investigated the cost difference of
      patient-owned versus hospital-provided CPAP machine use by admitted adult
      patients with OSA. STUDY DESIGN: Prospective cohort study at a tertiary academic
      center. METHODS: All new-patient admissions >18 years of age who were prescribed
      CPAP while inpatients over a 2-month period were included. Demographic
      information was collected, and cost analysis was performed. RESULTS: CPAP was
      used for 162 (1.2%) admissions. Mean patient age was 59 +/- 13 years; the
      majority were white (56.8%) and male (64.2%). Average CPAP utilization was 5.3 +/
      5.5 nights. The differential cost per day for patients using hospital-provided
      CPAP was $416.10 more than for patients using home CPAP machines. This cost
      included direct costs of an extended respiratory therapy (RT) initial visit,
      machine rental fee ($27.50), and additional RT evaluation time (mean, 85-145
      relative value units). The base initial visit was the same for all patients. Over
      the 2-month study period, the total cost difference in charges was $195,912; this
      extrapolates to $1,175,471 yearly. CONCLUSIONS: This is the first study to
      characterize the magnitude of cost savings from utilization of home versus
      hospital-provided CPAP machines in patients requiring inpatient CPAP machine use.
      The use of patient-owned CPAP machines may reflect an opportunity to provide
      cheaper care while maintaining high patient safety and quality care. The actual
      economic impact to an individual hospital would vary based on the insurance payer
      mix.

PMID- 24448723
TI  - Obesity-associated gastrointestinal tract cancer: from beginning to end.

PMID- 24448724
TI  - Mesh contraction: in vivo documentation of changes in apparent surface area
      utilizing meshes visible on magnetic resonance imaging in the rabbit abdominal
      wall model.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to analyze the apparent contraction of
      meshes in vivo after abdominal wall reconstruction and evaluate histological and
      biomechanical properties after explantation. METHODS: Nine New Zealand female
      rabbits underwent repair of two full-thickness 25 * 30-mm midline defects in the
      upper and lower parts of the abdomen. These were primarily overlaid by 35 * 40-mm
      implants of a polyvinylidene fluoride (PVDF) DynaMesh (n = 6) or polypropylene
      meshes Ultrapro (n = 6) and Marlex (n = 6). Edges of the meshes were secured with
      iron(II,III) oxide (Fe(3)O(4))-loaded PVDF sutures. Magnetic resonance images
      (MRIs) were taken at days 2, 30 and 90 after implantation. The perimeter of the
      mesh was traced using a 3D spline curve. The apparent surface area or the area
      within the PVDF sutures was compared with the initial size using the one-sample t
      test. A two-way repeat analysis of variance (ANOVA) was used to compare the
      apparent surface area over time and between groups. RESULTS: PVDF meshes and
      sutures with Fe(3)O(4) could be well visualized on MRI. DynaMesh and Marlex each
      had a 17 % decrease in apparent surface area by day 2 (p < 0.001 and p = 0.001),
      respectively, which persisted after day 90. Whereas there was a decrease in
      apparent surface area in Ultrapro, it did not reach significance until day 90 (p
      = 0.01). Overall, the apparent surface area decreased 21 % in all meshes by day
      90. No differences in histological or biomechanical properties were observed at
      day 90. CONCLUSIONS: There was a reduction in the apparent surface area between
      implantation and day 2, indicating that most mesh deformation occurs prior to
      tissue in-growth.

PMID- 24448726
TI  - Psychosexual outcome after labiaplasty: a prospective case-comparison study.
AB  - INTRODUCTION AND HYPOTHESIS: Our goal was to determine psychosexual outcome after
      labiaplasty in the long-term with specific measures of genital body image and
      sexual dysfunction. METHOD: We conducted a prospective study with a matched
      comparison group of women not wanting labiaplasty. Forty-nine women were compared
      against a group of 39 women matched for age, sexual orientation, ethnicity, and
      marital status. The labiaplasty group was assessed before, 3 months after and
      between 11 and 42 months after surgery. The comparison group was assessed at two
      time points 3 months apart to control for the passage of time. The primary
      outcome measure was the Genital Appearance Satisfaction (GAS) scale. RESULTS: Of
      the 49 women receiving labiaplasty, 19 (38.8 %) were lost to follow-up but were
      reassessed clinically. Twenty-four of 25 (96 %) women in the labiaplasty group
      showed a reliable and clinically significant improvement on the GAS scale 3
      months after the procedure; 21/23 (91.3 %) showed an improvement at the long-term
      follow-up. A large effect size was found for improvements on the GAS scale in the
      labiaplasty group. Small-effect sizes were found for improvements in sexual
      functioning. Nine women obtaining labiaplasty met diagnostic criteria for body
      dysmorphic disorder before the operation; eight lost that diagnosis at the 3
      month follow-up; 26 % reported minor side effects. CONCLUSIONS: Labiaplasty is
      effective in improving genital appearance and sexual satisfaction, but larger
      studies are required to determine the prevalence of potential side effects.

PMID- 24448725
TI  - Long-term follow-up after colpocleisis: regret, bowel, and bladder function.
AB  - INTRODUCTION AND HYPOTHESIS: Colpocleisis is not a popular option amongst
      surgeons, possibly due to concern about long-term regret. This study assessed a
      cohort of women who underwent colpocleisis 2-5 years previously to determine the
      regret rate, the effect on quality of life (QOL) and bladder and bowel function.
      METHODS: This was a longitudinal study of patients who underwent colpocleisis at
      least 2 years previously. Participants were asked to complete the Prolapse QOL (P
      QOL), International Consultation on Incontinence-Urinary Incontinence (ICIQ-UI
      Short Form) and Colorectal Anal Distress Inventory questionnaires (CRADI). Two
      additional questions were asked: (1) Do you regret having vaginal closure surgery
      for prolapse? (never, sometimes, often, all the time), and (2) Would you
      recommend this surgery to a relative or friend who is not sexually active? (yes,
      no.) RESULTS: Thirty-four women were identified. Six had died by the time of
      follow-up, and five declined to answer the questionnaires because of ill health.
      Twenty-three women responded (67 %). Mean age was 78.68 years. One woman
      regretted having had the surgery, as the colpocleisis had failed. Twenty-one
      women (91.3 %) would recommend this surgery; one would not (4.3 %), and another
      was not sure (4.5 %). Low P-QOL [8 (0-37) +/- 9.41), ICIQ-UI (7 (0-17) +/- 5.44)
      and CRADI (10; 0-28 +/- 8.13] scores suggest a positive impact on QOL, bladder
      and bowel function. CONCLUSION: In this cohort, colpocleisis produced a good
      outcome with low regret rate (4.3 %), good QOL and minimal effect on bladder and
      bowel function at 2-5 years.

PMID- 24448727
TI  - Female genital mutilation reversal: a general approach.
AB  - INTRODUCTION AND HYPOTHESIS: Female genital mutilation (FGM) is a violation of
      human rights; yet, more than 100 million females are estimated to have undergone
      the procedure worldwide. There is an increased need for physician education in
      treating FGM. Female pelvic surgeons have a unique opportunity to treat this
      population of patients. Here, we depict the classification of FGM and a general
      approach to FGM reversal. We specifically address the procedure of type III FGM
      reversal, or defibulation. METHODS: In this video, we first highlight the
      importance of the problem of FGM. Next, we present the classification of FGM
      using an original, simple, schematic diagram highlighting they key anatomic
      structures involved in the four types of FGM. We then present a simple case of
      reversal of type III FGM, a procedure also known as defibulation. After depicting
      the surgical procedure, we discuss clinical results and summarize key principles
      of the defibulation procedure. RESULTS: Our patient was a 25-year-old woman who
      had undergone type III FGM as a child in Somalia. She desired restoration of
      vaginal function. We performed a reversal, and her postoperative course was
      uncomplicated. By 6 weeks postoperatively, she was able to engage in sexual
      intercourse without dyspareunia. CONCLUSION: FGM is a problem at the doorsteps of
      female pelvic medicine and reconstructive surgery. Our video demonstrates a basic
      surgical approach that can be applied to simple cases of type III FGM presenting
      to the female pelvic surgeon.

PMID- 24448728
TI  - Urinary incontinence and prevalence of high depressive symptoms in older black
      versus white women.
AB  - INTRODUCTION AND HYPOTHESIS: Previous studies report higher prevalence of
      depression among women with urgency (UUI) or mixed (MUI) urinary incontinence
      than those with stress UI (SUI). UUI is the dominant type among black women,
      whereas SUI is the predominant type among white women. Thus, UI-related mental
      health issues could be a key consideration among black women. We hypothesized
      that the association between UI and depression might be stronger in black versus
      white women. METHODS: These cross-sectional analyses assessed 934 black and
      71,161 white women aged 58-83 in the Nurses' Health Study, which was established
      among women living in the USA. Depressive symptoms were assessed using the ten
      item Center for Epidemiologic Studies Depression Scale (CESD-10). Multivariate
      adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) for high
      depressive symptoms (CESD-10 score >= 10) according to self-reported UI
      frequency, severity, and type were calculated using logistic regression models.
      RESULTS: Although point estimates for associations of UI frequency, severity, and
      type with high depressive symptoms were higher in black women, differences in ORs
      between black versus white women were not statistically significant. For example,
      the OR for at least weekly UI compared with no UI was 2.29 (95 % CI 1.30-4.01) in
      black women and 1.58 (95 % CI 1.49-1.68) in white women (p interaction = 0.4).
      CONCLUSIONS: We found no statistically significant differences in UI frequency,
      severity, and type with high depressive symptoms in black versus white women.
      However, the small number of black women in this study with high depressive
      symptoms limited statistical power to detect significant interactions. Thus,
      these results should be interpreted with caution.

PMID- 24448729
TI  - Lack of correlation between coronary blood flow and carotid intima media
      thickness.
AB  - BACKGROUND: The phenomenon of slow coronary flow (SCF) in the presence of normal
      coronary arteries may indicate endothelial dysfunction, which is characteristic
      of an early stage in the development of atherosclerosis. Measurement of the
      Carotid Intima-Media Thickness (CIMT) allows identification of early stages of
      atherosclerosis. CIMT might offer a non-invasive method of diagnosing SCF
      patients. Previous studies demonstrated conflicting results regarding the
      relationship between these two phenomena. In the present study, we examined the
      association between coronary flow velocity and the degree of CIMT in patients
      with angiographically normal coronary arteries. METHODS: Coronary arterial blood
      flow velocity was measured using two methods - Corrected Thrombolysis in
      Myocardial Infarction (TIMI) Frame Count (CTFC) and Coronary Clearance Frame
      Count (CCFC). In addition, we measured the level of the CIMT using a special
      automated computerized software. RESULTS: Seventy Five consecutive patients were
      prospectively recruited. No correlation was found between CIMT and mean CTFC (r =
      -0.08, p = NS) or mean CCFC (r = -0.07, p = NS). In addition, CIMT values did not
      differ between the SCF and the Normal coronary flow (NCF) groups (0.796 mm vs.
      0.805 mm, respectively, p = 0.733). Patients with SCF had higher levels of
      hematocrit (39.9% vs. 36.1%, p < 0.001), LDL cholesterol (101.1 mg/dl vs. 85.8
      mg/dl, p = 0.01) and higher rate of current smokers (28.9% vs. 10.8%, p = 0.05).
      CONCLUSIONS: Patients with angiographically normal coronary arteries and SCF do
      not have increased CIMT values. However, current smoking, higher LDL cholesterol
      and hematocrit levels are all related to slower coronary blood flow.

PMID- 24448730
TI  - Clinical evaluation of the intestinal microcirculation using sidestream dark
      field imaging--recommendations of a round table meeting.
AB  - INTRODUCTION: In clinical setting, Sidestream Dark Field (SDF) imaging has
      provided unprecedented insights into the gut microcirculation mainly by studying
      the intestinal mucosa of patients with ileostomies. Visualizing microvascular
      structure and function of ileal mucosa at the bedside brings unique opportunity
      for clinical research, particularly in critically ill patients. Several papers
      that were focused on intestinal microcirculation, used different methods of
      assessment because an accepted scoring systems does not exist so far and it is no
      surprise that it is rather difficult to compare the results from these studies.
      The present paper presents recommendations concerning specific aspects of image
      acquisition and proposes some parameters for the description of the intestinal
      microcirculation in human studies, as suggested by the participants of a round
      table meeting. METHODS: The round table meeting participants reviewed all
      relevant literature, discussed various aspects of image acquisition by SDF
      technology in patients with ileostomy and parameters for the description of
      intestinal mucosa microcirculation. Selected key conditions for high quality and
      reproducible image recordings were identified. To evaluate quality of intestinal
      microcirculation, selected parameters and scoring system were suggested and
      described. RESULTS: For image acquisition in ileostomies, five key points were
      proposed: optimal timing, optimal SDF device probe positioning, optimal
      stabilization, optimal number and length of acquired video recordings, and
      optimal avoidance of pressure artefacts. With regard to image analysis,
      simplified set of quantitative and qualitative parameters for the description of
      the intestinal mucosa microcirculation for the clinical studies has been
      proposed: vessels per villus, microvascular flow index, proportion of perfused
      villi, and borders of villi. The proposed parameters can be included in a semi
      quantitative scoring system; however, this scoring system needs further
      validation. This simplified analysis does not require sophisticated software and
      can be performed manually on the video screen. CONCLUSION: We propose a simple
      methodology for image acquisition and suggest specific microvascular parameters
      to analyze SDF imaging studies of the intestinal mucosa microcirculation in
      patients with ileostomy. Proposed scoring system needs to be validated in further
      clinical studies.

PMID- 24448731
TI  - Percutaneous biopsies of splenic lesions--a clinical and contrast enhanced
      ultrasound based algorithm.
AB  - OBJECTIVE: Splenic lesions are rare and characterization is difficult. Secondary
      spread is more frequent than primary malignant lesions. Thus clinical
      circumstances are important in the general work-up. Contrast enhanced ultrasound
      (CEUS) had high accuracy in recent studies but the positive predictive value is
      low. Biopsy is considered dangerous. Recent studies have brought back this method
      into focus showing an excellent efficacy and safety. The aim of this study was to
      estimate the rate of relevant biopsy results in patients with splenic lesions
      concerning the clinical circumstances. DESIGN: Patients with unclear splenic
      lesions which appeared progressively hypoenhancing in the late phase of CEUS with
      BR1 were included. Biopsy was performed with ultrasound guidance. Patients were
      sorted into 5 groups according to their clinical symptoms. RESULTS: 44 patients
      were enrolled, 59% had benign lesions. 73% were rated relevant. For the subgroups
      the rate was: patients with hints for hemato-oncological diseases 83%, patients
      without symptoms 38%, patients with infections of unknown origin 100%, patients
      with suspicion of metastases 33%, immunocompromised patients 100%. One bleeding
      could be managed conservatively, another bleeding was detected incidentally 2
      weeks later. CONCLUSION: Percutaneous biopsy of unclear splenic lesions which
      appear hypoenhancing in the late phase of CEUS with BR1 results in a high rate of
      relevant lesions. The results should be tested in larger numbers of patients.

PMID- 24448732
TI  - The impacts of super obesity versus morbid obesity on red blood cell aggregation
      and deformability among patients qualified for bariatric surgery.
AB  - The aim of this study was to evaluate the effects of the obesity degree on red
      blood cell aggregation and deformability. We studied 56 obese patients before
      weight loss surgery who were divided into two groups: morbid obesity and super
      obesity. The aggregation and deformability of RBCs were evaluated using a Laser
      assisted Optical Rotational Cell Analyzer (Mechatronics, the Netherlands). The
      following parameters specific to the aggregation process were estimated:
      aggregation index (AI), aggregation half-time (t1/2) and threshold shear rate
      (gammathr). RBC deformability was expressed as erythrocyte elongation (EI), which
      was measured at 18.49 Pa and 30.2 Pa shear stresses. Super obese patients
      presented significantly higher AI (P < 0.05) and gammathr (P < 0.05) and
      significantly lower t1/2 (P < 0.05) compared with morbidly obese individuals.
      Multivariate analyses showed that fibrinogen (beta 0.46, P < 0.01 and beta 0.98,
      P < 0.01) and hematocrit (beta 0.38, P < 0.05 and beta 1.01, P < 0.01)
      independently predicted the AI in morbidly obese and super obese patients.
      Fibrinogen (beta -0.4, P < 0.05 and beta -0.91, P < 0.05) and hematocrit (beta 
      0.38, P < 0.05 and beta -1.11, P < 0.01) were also independent predictors of the
      t1/2 in both obese groups. The triglyceride level (beta 0.32, P < 0.05) was an
      independent predictor of the t1/2 in the morbidly obese group. No differences in
      EI were observed between obese subjects. Multivariate analyses showed that the
      triglyceride level independently predicted EI at 18.49 Pa (beta -0.42, P < 0.05
      and beta -0.53, P < 0.05) and 30.2 Pa (beta -0.44, P < 0.01 and beta -0.49, P <
      0.05) in both obese groups. This study indicated that the obesity degree of
      patients who qualify for bariatric surgery affects RBC aggregation properties,
      but it does not indicate the reasons for this difference. Further studies are
      needed to determine factors associated with hyperaggregation in super obesity. 

PMID- 24448733
TI  - Investigation of hemorheological parameters at the diagnosis and follow up of
      children with iron deficiency anemia and mixed anemia.
AB  - OBJECTIVE: We aimed to investigate the effects of iron deficiency anemia (IDA)
      and vitamin B12 deficiency coexisting with IDA which is called as mixed anemia
      (MA) on hemorheological parameters, to compare them with each other and healthy
      controls, and to assess the changes in hemorheological parameters after
      treatment. MATERIALS AND METHODS: 32 IDA patients (mean age:6.3 +/- 5.3 years),
      30 MA patients (mean age:7.2 +/- 5.4 years), and 31 healthy controls (mean
      age:7.1 +/- 5.2 years) were enrolled. Erythrocyte deformability and aggregation
      were determined by an ectacytometer, plasma and whole blood viscosities by a cone
      plate rotational viscometer. Differences between IDA and MA, and healthy controls
      were compared. Hemorheological parameters were repeated in the patient groups
      after treatment and compared with the initial results. RESULTS: In both of the
      patient groups, erythrocyte deformability, whole blood and plasma viscosities
      were found to be significantly decreased before treatment, compared with the
      controls. After treatment these parameters were found to be increased
      significantly. There were no significant differences in these parameters between
      the IDA and MA group. Additionally, no statistically significant alteration was
      found in erythrocyte aggregation measurements of both patient groups. CONCLUSION:
      This study indicates that IDA and MA have similar effects on hemorheological
      parameters. When vitamin B12 deficiency accompanies IDA which is called as MA, no
      further alterations occur in hemorheological parameters. The adequate treatment
      of these anemias not only corrects the hematological parameters, but also by
      helping to normalize the hemorheological parameters, may contribute to the
      regulation of microvascular perfusion.

PMID- 24448734
TI  - An ebselen like catalyst with enhanced GPx activity via a selenol intermediate.
AB  - The reaction of KSeO(t)Bu with 2-iodo-arylbenzamides gave benzamide ring
      substituted, quinine-derived isoselenazolones 1b-1d. The reaction of PhSH with
      ortho-methyl-substituted isoselenazolone 1b gave selenol 3b, which is oxidized by
      H2O2 to regenerate 1b. Isoselenazolone 1b shows a high rate (0.33 * 103 MUM min(
      1)) of oxidation of PhSH with H2O2, which is ~103-fold more active than ebselen
      (1a) and >=30-fold more active than the other isoselenazolones of this study.
      Compound 1b shows less inhibition of the growth of yeast cells than 1a.

PMID- 24448736
TI  - Noninvasive and invasive ventilation and enteral nutrition for ALS in Italy.
AB  - INTRODUCTION: We performed a population-based study to assess amyotrophic lateral
      sclerosis (ALS) survival after noninvasive ventilation (NIV), invasive
      ventilation (IV), and enteral nutrition (EN). METHODS: We included patients
      diagnosed from 2000 to 2009 in Modena, where a prospective registry and a Motor
      Neuron Diseases Centre have been active since 2000. RESULTS: Of the 193 incident
      cases, 47.7% received NIV, 24.3% received tracheostomy, and 49.2% received EN. A
      total of 10.4% of the patients refused NIV, 31.6% refused IV, and 8.7% refused
      EN. The median survival times after NIV, IV, and EN were 15, 19, and 9 months,
      respectively. Of the tracheostomized patients, 79.7% were discharged from the
      hospital; 73.0% were discharged to home. The median survival times for
      tracheostomized patients who were cared for at home and in nursing homes were 43
      and 2 months, respectively. The multivariate analysis demonstrated that the place
      of discharge was the only independent prognostic factor after IV (P<0.01).
      CONCLUSIONS: Service organizations may promote adherence to NIV, IV, EN, and
      influence postprocedure survival. These data may be useful in defining health
      plans regarding advanced ALS care and in patient counseling.

PMID- 24448735
TI  - Reward prospect rapidly speeds up response inhibition via reactive control.
AB  - Response inhibition is an important cognitive-control function that allows for
      already-initiated or habitual behavioral responses to be promptly withheld when
      needed. A typical paradigm to study this function is the stop-signal task. From
      this task, the stop-signal response time (SSRT) can be derived, which indexes how
      rapidly an already-initiated response can be canceled. Typically, SSRTs range
      around 200 ms, identifying response inhibition as a particularly rapid cognitive
      control process. Even so, it has recently been shown that SSRTs can be further
      accelerated if successful response inhibition is rewarded. Since this earlier
      study effectively ruled out differential preparatory (proactive) control
      adjustments, the reward benefits likely relied on boosted reactive control. Yet,
      given how rapidly such control processes would need to be enhanced, alternative
      explanations circumventing reactive control are important to consider. We
      addressed this question with an fMRI study by gauging the overlap of the brain
      networks associated with reward-related and response-inhibition-related processes
      in a reward-modulated stop-signal task. In line with the view that reactive
      control can indeed be boosted swiftly by reward availability, we found that the
      activity in key brain areas related to response inhibition was enhanced for
      reward-related stop trials. Furthermore, we observed that this beneficial reward
      effect was triggered by enhanced connectivity between task-unspecific (reward
      related) and task-specific (inhibition-related) areas in the medial prefrontal
      cortex (mPFC). The present data hence suggest that reward information can be
      translated very rapidly into behavioral benefits (here, within ~200 ms) through
      enhanced reactive control, underscoring the immediate responsiveness of such
      control processes to reward availability in general. 

PMID- 24448737
TI  - Therapy for patients with antibodies to complement factor H associated HUS.

PMID- 24448738
TI  - Amino acid change in the carbohydrate response element binding protein is
      associated with lower triglycerides and myocardial infarction incidence depending
      on level of adherence to the Mediterranean diet in the PREDIMED trial.
AB  - BACKGROUND: A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like
      protein X interacting protein-like) gene encoding the carbohydrate response
      element binding protein has been associated with lower triglycerides. However,
      its association with cardiovascular diseases and gene-diet interactions
      modulating these traits are unknown. METHODS AND RESULTS: We studied 7166
      participants in the PREvencion with DIeta MEDiterranea trial testing a
      Mediterranean diet (MedDiet) intervention versus a control diet for
      cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids,
      MLXIPL polymorphisms, and cardiovascular events were assessed. Data were analyzed
      at baseline and longitudinally. We used multivariable-adjusted Cox regression to
      estimate hazard ratios for cardiovascular outcomes. The MLXIPL-rs3812316 was
      associated with lower baseline triglycerides (P=5.5*10(-5)) and lower
      hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63-0.85;
      P=1.4*10(-6) in G-carriers versus CC). This association was modulated by baseline
      adherence to MedDiet. When adherence to MedDiet was high, the protection was
      stronger (odds ratio, 0.63; 95% CI, 0.51-0.77; P=8.6*10(-6)) than when adherence
      to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70-1.09; P=0.219). Throughout the
      follow-up, both the MLXIPL-rs3812316 (P=3.8*10(-6)) and the MedDiet intervention
      (P=0.030) were significantly associated with decreased triglycerides. Likewise in
      G-carriers MedDiet intervention was associated with greater total cardiovascular
      risk reduction and specifically for myocardial infarction. In the MedDiet, but
      not in the control group, we observed lower myocardial infarction incidence in G
      carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12-0.93; P=0.036 and 0.90; 95%
      CI, 0.35-2.33; P=0.830, respectively). CONCLUSIONS: Our novel results suggest
      that MedDiet enhances the triglyceride-lowering effect of the MLXIPL-rs3812316
      variant and strengthens its protective effect on myocardial infarction incidence.
      CLINICAL TRIAL REGISTRATION: URL: www.controlled-trials.com. Unique Identifier:
      ISRCTN35739639.

PMID- 24448739
TI  - Comparison of the serum lipidome in patients with abdominal aortic aneurysm and
      peripheral artery disease.
AB  - BACKGROUND: Currently, the relationship between circulating lipids and abdominal
      aortic aneurysm (AAA) is unclear. We conducted a lipidomic analysis to identify
      serum lipids associated with AAA presence. Secondary analyses assessed the
      ability of models incorporating lipidomic features to improve stratification of
      patient groups with and without AAA beyond traditional risk factors. METHODS AND
      RESULTS: Serum lipids were profiled via liquid chromatography tandem mass
      spectrometry analysis of serum from 161 patients with AAA and 168 controls with
      peripheral artery disease. Binary logistic regression was used to identify AAA
      associated lipids. Classification models were created based on a combination of
      (1) traditional risk factors only or (2) lipidomic features and traditional risk
      factors. Model performance was assessed using receiver operator characteristic
      curves. Three diacylglycerols and 7 triacylglycerols were associated with AAA.
      Combining lipidomic features with traditional risk factors significantly improved
      stratification of AAA and peripheral artery disease groups when compared with
      traditional risk factors alone (mean area under the receiver operator
      characteristic curve [95% confidence interval], 0.760 [0.756-0.763] and 0.719
      [0.716-0.723], respectively; P<0.05). CONCLUSIONS: A group of linoleic acid
      containing triacylglycerols and diacylglycerols were significantly associated
      with AAA presence. Inclusion of lipidomic features in multivariate analyses
      significantly improved prediction of AAA presence when compared with traditional
      risk factors alone.

PMID- 24448740
TI  - Synthesis of [3alpha-(3) H] 17alpha-hydroxy pregnenolone and [3alpha-(3) H]
      pregnenolone.
AB  - For the first time, [3alpha-(3) H] 17alpha-hydroxy pregnenolone (1) was
      synthesized through a multiple step sequence. The presence of [3beta-(3) H]
      isomer in RP-HPLC purified product was identified by tritium NMR. The [3beta-(3)
      H] isomer was then separated from [3alpha-(3) H] 17alpha-hydroxy pregnenolone
      with chiralPAK AD-H column. [3alpha-(3) H] pregnenolone (2) was synthesized from
      commercial available 5-pregnen-3,20-dione in one step with an improved procedure.

PMID- 24448741
TI  - Preparation and biological evaluation of (99m) TcN-labeled pteroyl-lys derivative
      as a potential folate receptor imaging agent.
AB  - In order to develop a novel (99m) Tc-labeled folate receptor (FR) imaging agent,
      a dithiocarbamate derivative, pteroyl-lys-DTC, was synthesized and radiolabeled
      with (99m) Tc through the [(99m) TcN](2+) intermediate. The radiochemical purity
      of the corresponding (99m) Tc-complex, (99m) TcN-pteroyl-lys-DTC, was over 95% as
      measured by reversed-phase HPLC. The (99m) TcN complex was stable under
      physiological conditions. (99m) TcN-pteroyl-lys-DTC exhibited specific FR binding
      in FR-positive KB cells in vitro. The biodistribution in tumor-bearing mice
      showed that the (99m) TcN-labeled radiotracer had good uptake (3.56 +/- 0.09%ID/g
      at 2 h postinjection) in FR-positive KB tumors, as well as in the kidneys (30.34
      +/- 3.53%ID/g at 2 h postinjection). After coinjection with excess folic acid,
      the uptake in tumor and kidneys was significantly blocked. The results indicated
      that (99m) TcN-pteroyl-lys-DTC was able to target the FR-positive tumor cells and
      tissues specifically both in vitro and in vivo.

PMID- 24448742
TI  - Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for
      tau imaging.
AB  - Alzheimer's disease (AD) is the most common cause of dementia. Senile plaques,
      consisting of beta-amyloid, and neurofibrillary tangles (NFTs), composed of tau
      protein, are representative pathological hallmarks of AD. It is believed that the
      accumulation of NFTs precedes the onset of clinical symptoms of AD and correlates
      with the progression of memory dysfunction. Thus, the use of noninvasive
      detection techniques including radiolabeled probes and positron emission
      tomography (PET) will facilitate early diagnosis or staging of AD. In this study,
      we synthesized and evaluated novel hydroxylated 2-arylquinoline derivatives as
      tau imaging PET probes. The binding affinities of compounds for tau were
      evaluated by fluorescent staining of the AD hippocampal section and a competitive
      binding assay using [(18) F]THK-523. THK-951 showed high binding affinity for tau
      pathology in an AD brain section and K18Delta280K fibrils (Ki  = 20.7 nM); thus,
      we radiosynthesized a (11) C-labeled THK-951 and further studied its potential as
      a tau PET probe. The [(11) C]THK-951 demonstrated excellent kinetics in a normal
      mouse brain (3.23% ID/g at 2 min postinjection and 0.15% ID/g at 30 min
      postinjection) and showed the labeling of NFTs in an AD brain section by
      autoradiography assay. These findings indicate the availability of [(11) C]THK
      951 for in vivo PET imaging of tau pathology in AD.

PMID- 24448743
TI  - Preparation of clinical-grade (89) Zr-panitumumab as a positron emission
      tomography biomarker for evaluating epidermal growth factor receptor-targeted
      therapy.
AB  - Panitumumab is a fully human monoclonal antibody approved for the treatment of
      epidermal growth factor receptor (EGFR) positive colorectal cancer. Recently,
      panitumumab has been radiolabeled with (89) Zr and evaluated for its potential to
      be used as immuno-positron emission tomography (PET) probe for EGFR positive
      cancers. Interesting preclinical results published by several groups of
      researchers have prompted us to develop a robust procedure for producing clinical
      grade (89) Zr-panitumumab as an immuno-PET probe to evaluate EGFR-targeted
      therapy. In this process, clinical-grade panitumumab is bio-conjugated with
      desferrioxamine chelate and subsequently radiolabeled with (89) Zr resulting in
      high radiochemical yield (>70%, n = 3) and purity (>98%, n = 3). All quality
      control (QC) tests were performed according to United States Pharmacopeia
      specifications. QC tests showed that (89) Zr-panitumumab met all specifications
      for human injection. Herein, we describe a step-by-step method for the facile
      synthesis and QC tests of (89) Zr-panitumumab for medical use. The entire process
      of bioconjugation, radiolabeling, and all QC tests will take about 5 h. Because
      the synthesis is fully manual, two rapid, in-process QC tests have been
      introduced to make the procedure robust and error free.

PMID- 24448744
TI  - The development of an automated and GMP compliant FASTlabTM Synthesis of [(18)
      F]GE-180; a radiotracer for imaging translocator protein (TSPO).
AB  - The level of the translocator protein (TSPO) increases dramatically in microglial
      cells when the cells are activated in response to neuronal injury and insult. The
      radiotracer [(18) F]GE-180 binds selectively and with high affinity to TSPO and
      can therefore be used to measure neuroinflammation in a variety of disease
      states. An optimized, automated synthesis of [(18) F]GE-180 has been developed
      for the GE FASTlabTM synthesizer. The entire process takes place on the single
      use cassette. The radiolabelling is performed by nucleophilic fluorination of the
      S- enantiomer mesylate precursor. The crude product is purified post
      radiolabelling using two solid-phase extraction cartridges integrated on the
      cassette. Experimental design and multivariate data analysis were used to assess
      the robustness, and critical steps were optimized with respect to efficacy and
      quality. The average radiochemical yield is 48% (RSD 6%, non-decay corrected),
      and the synthesis time including purification is approximately 43 min. The
      radiochemical purity is >=95% for radioactive concentration <=1100 MBq/mL. The
      total amount of precursor-related chemical impurities is 1-2 ug/mL. The use of
      solid-phase extraction purification results in a robust GMP compliant process
      with a product of high chemical and radiochemical purity and consistent
      performance across positron emission tomography (PET) centers. 

PMID- 24448745
TI  - Influence of radiolytic-produced hydrogen peroxide on the stability of commercial
      kit (99m) technetium-exametazime preparation.
AB  - 99mTc-d,l-hexamethylpropylene amine oxime ((99m) Tc-d,l-HMPAO) is a widely used
      radiopharmaceutical that suffers from an inherent instability with a shelf life
      of 30 min that constrains its availability for clinical use. A protocol for
      improving the stability of the kit with minimal modification of manufacturer's
      instructions and no chemicals addition to the commercial formulation is proposed.
      The protocol is based on the displacement of the oxygen present in the
      preparation, preventing free radicals build up and free pertechnetate formation.
      Although the degradation of (99m) Tc-d,l-HMPAO cannot be explained solely by the
      radiolytic production of free radicals, it appears to be an important factor in
      the shelf stability of the complex.

PMID- 24448746
TI  - Evaluation of the efficiency of Pd/H2 -catalyzed benzylic H/D exchange of
      dehydroabietinal with D(2) O and synthesis of a tritium-labeled analogue.
AB  - Dehydroabietinal (DA) has been identified as an important signaling molecule in
      systemic acquired resistance in plants. Deuterium and tritium-labeled DA were
      synthesized to confirm its role in signaling and to further elucidate the
      mechanism by which DA induces systemic acquired resistance. Pd/H2 -catalyzed
      exchange of benzylic hydrogen atoms of DA with (2) H-H2 O or (3) H-H2 O was
      conducted with >97% label incorporation for (2) H-DA and a specific activity of
      12.6 mCi/mmol for (3) H-DA synthesized from 90 mCi/mmol (3) H-H2 O. The extent of
      deuterium labeling at each benzylic position was determined via an inverse-gated
      (13) C NMR experiment. C7 and C15 were 87% and 81% labeled, respectively. Isotope
      induced chemical shift changes at C6 were used to approximate the amount of
      singly (66%) and doubly (17%) labeled (2) H-DA at C7. Results also indicated that
      two of the three benzylic protons in DA underwent facile exchange. Exchange at
      the remaining position was likely hampered by steric interactions of nearby
      methyl groups at the surface of the Pd catalyst. 

PMID- 24448748
TI  - Novel meso-superstructured solar cells with a high efficiency exceeding 12%.
AB  - The dye-sensitized solar cell (DSSC) is representative of next generation
      photovoltaic devices. State-of-the-art DSSCs have been established for two
      decades. However, the recent application of organic-inorganic hybrid perovskites
      on nanoparticle Al2 O3 film has totally changed the DSSC structure, leading to a
      new type of solar cell - meso-superstructured solar cells (MSSCs) with a high
      power conversion efficiency exceeding 12%. This article summarizes this
      impressive progress and discusses the challenges of MSSCs. 

PMID- 24448749
TI  - Should we blame the rich for clogging our landfills?
AB  - Conventional wisdom often holds that relatively high consumption levels among the
      affluent contributes to the generation of high volumes of municipal solid waste
      (MSW). Comparing data from different cities in Israel suggests otherwise.
      Regression analysis reveals that aggregate per capita waste outputs of cities are
      only vaguely correlated with their socio-economic indicators. In fact, the
      apparent 'hedonic' waste of the richest cities, compared with the average ones,
      accounts for only about 2% of the total waste production. Israel's main economic
      area, the Tel Aviv district, produces a quarter more MSW per capita than other
      districts, suggesting a need for special attention by policy makers. A
      surprisingly strong predicator of MSW per capita is water consumption by
      municipalities, dedicated for public gardening. The trimmings of the municipal
      landscape constituting an unobserved fraction of total MSW data, are estimated to
      be responsible for 15% of Israel's MSW, making it an additional target area for
      consideration and intervention. 

PMID- 24448750
TI  - High NF-kappaB and STAT3 activity in human urothelial carcinoma: a pilot study.
AB  - PURPOSE: Given that the tumor-promoting inflammation has been previously
      established in squamous cell carcinoma of the bladder but its contribution to
      development of urothelial carcinoma (UC) still remains elusive, our aim was to
      study changes in expression and activity of inflammation-mediating NF-kappaB and
      STAT3 transcription factors in human urothelial bladder carcinoma as well as
      expression of their target genes cyclin D1, VEGFA and TGFbeta1. METHODS: Gene
      expression of STAT3, NF-kappaB, TGFbeta1, cyclin D1 and VEGFA was measured by
      quantitative real-time polymerase chain reaction in both tumor and healthy
      bladder tissue from 36 patients with UC of the bladder. Activation of STAT3 and
      NF-kappaB was assessed with immunohistochemistry and immunoblot. RESULTS:
      Urothelial bladder carcinoma displayed elevated expression as well as activation
      of NF-kappaB (P = 5.38e-10) and STAT3 (P = 0.002) transcription factors.
      Furthermore, elevated level of expression was observed for cyclin D1, VEGFA and
      TGFbeta1 (P = 9.71e-09, P = 9.71e-09, P = 5.38e-10). Preliminary statistical
      analysis indicated that the level of upregulation of STAT3 or NF-kappaB was
      probably not dependent upon the grade (P = 0.984 and 0.803, respectively) and
      invasiveness of the tumor (0.399 and 0.949), nor to the gender (0.780 and 0.536)
      and age (0.660 and 0.816) of the patients. CONCLUSIONS: NF-kappaB and STAT3
      signaling pathways, as main inflammatory mediators, are found to be activated in
      urothelial bladder carcinoma indicating that chronic inflammatory processes are
      accompanying development of this tumor type. Future studies will have to
      determine possible causative role of inflammatory processes in development of
      urothelial bladder carcinomas.

PMID- 24448751
TI  - Cardiac troponin T elevation associated with transient global amnesia: another
      differential diagnosis of 'troponosis'.
AB  - Elevated cardiac troponin (cTn) levels can be detected in a variety of diseases
      with or without signs of myocardial ischaemia. Acute neurological disorders such
      as subarachnoid haemorrhage, stroke, transient ischaemic attack, epileptic
      seizures, and traumatic head injury can cause cTn elevation with and without
      myocardial wall motion abnormalities. We report a case of transient global
      amnesia with elevation and dynamic rise of highly sensitive troponin T (hsTnT)
      without clinical symptoms or signs of ischaemia. Cardiac work up was otherwise
      normal, with no signs of atherosclerotic coronary artery disease on coronary
      angiogram. Myocardial systolic function was also normal. In the era of highly
      sensitive cTn assays, dynamic elevations of cTn are seen in a number of acute
      conditions unrelated to myocardial ischaemia. Transient global amnesia should be
      added to the list of acute neurological disorders where cTn release can be
      present, even in the absence of stress-induced cardiomyopathy. 

PMID- 24448752
TI  - Additional value of B-type natriuretic peptide on discrimination of patients at
      risk for mortality after a non-ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND: Few studies have addressed the additional value of B-type natriuretic
      peptide (BNP) on risk stratification in non-ST-elevation acute coronary syndrome
      (NSTE-ACS). We aimed to evaluate whether BNP levels provide additional
      improvement on discrimination and reclassification of patients at risk of
      mortality during admission and follow up after a NSTE-ACS. METHODS: BNP levels
      were measured 24-96 hours post admission in 600 patients with a NSTE-ACS. The
      incremental predictive value of including BNP into the multivariate models with
      the highest predictive accuracy for mortality during admission (logistic
      regression) and follow up (Cox regression) and over the Thrombolysis in
      Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE)
      risk scores was assessed using calibration, discrimination (area under the ROC
      curve (AUC) and Harrell's C statistic), and reclassification measures (net
      reclassification improvement (NRI) and index discrimination improvement (IDI)).
      RESULTS: A total of 19 (3.2%) patients died during admission and 29 (4.1%) during
      follow up (median 13.4 months). BNP was independently associated with mortality
      during admission (OR 3.56, 95% CI 1.75-7.23) and improved discrimination (AUC
      0.95 vs. 0.92, p=0.01) and reclassification (NRI 72% and IDI 8%, p<0.05 for
      both). Similarly, BNP was an independent predictor of mortality during follow up
      (HR 2.46, 95% CI 1.94-3.12) and provided additional discriminative value
      (Harrell's C 0.86 vs. 0.84, p=0.04). Similarly, BNP demonstrated additional value
      above the TIMI and GRACE scores. CONCLUSIONS: Determination of BNP 24-96 hours
      after a NSTE-ACS improved discrimination of patients at risk for mortality during
      admission and follow up.

PMID- 24448753
TI  - Overexpression of CDK5 in neural stem cells facilitates maturation of embryonic
      neurocytes derived from rats in vitro.
AB  - To further understand the effects of cyclin-dependent kinase 5 (CDK5) on the
      differentiation of neural stem cells, which were cultured and transfected with
      CDK5-EGFP recombinant overexpression vector (OV-CDK5 Group), successful
      transfection was confirmed by RT-PCR and Western blot. Our results showed that
      the CDK5 mRNA expression significantly increased in 6 h after transfection.
      Increase in the levels of the CDK5 protein expression was observed in 72 h,
      compared with Empty Vector Control Group (EV-CTL Group) (P < 0.01). Furthermore,
      in OV-CDK5 Group, the percentage of S-phase cells was significantly higher than
      in EV-CTL Group (P < 0.01). Differentiated cells were showed with short processes
      in 24 h and with obviously enlarged cell body, and extended cellular processes in
      72 h, in comparison to those in EV-CTL Group (P < 0.01). In 72 h under treatment
      with 10 MUmol/L all-trans retinoic acid (ATRA), in OV-CDK5 Group, processes of
      the GFP-positive cells were reduced slightly and little GFP-positive debris was
      found. However, in the EV-CTL Group, processes of the GFP-positive cells were
      obviously shortened and deformed and much GFP-positive debris were found.
      Moreover, the percentage of G0/G1-phase cells was lesser, while the percentage of
      S-phase cells was higher than that in EV-CTL Group (P < 0.01, P < 0.01). In
      conclusion, our experiment suggested that CDK5 might promote proliferation and
      differentiation of neural stem cells, lengthen the processes of differentiated
      neurocytes, and accelerate morphological maturation of such cells. Furthermore,
      CDK5 might antagonize ATRA-induced inhibition against proliferation and
      differentiation in differentiated neurocytes.

PMID- 24448754
TI  - Accuracy of nuchal translucency measurement depends on equipment used and its
      calibration.
AB  - OBJECTIVES: To determine the effect of different ultrasound machine-probe
      combinations on nuchal translucency (NT) measurements and to assess how this
      impacts on the accuracy of the NT-derived component of first-trimester screening
      for trisomy 21. METHODS: Sixteen different ultrasound machine-probe combinations
      were used for axial measurement of 2.0-, 3.0- and 4.0-mm spaced targets in an
      ultrasound phantom. Differences between the measured and known values were
      determined. The mean of the axial measurements was used to calculate adjusted
      risks for trisomy 21, given specific clinical scenarios. RESULTS: Differences
      observed using different machine-probe combinations for the 2.0-mm target ranged
      from 1.8-2.2 mm; for the 3.0-mm target, 2.7-3.2 mm; and for the 4-mm target, 3.7
      4.3 mm, and exceeded those due to intraobserver variability. For a fetal crown
      rump length of 50.0 mm and NT measurement of 2.0 mm, the maximum/minimum
      measurements in the fetus of a 40-year-old woman led to derived risks ranging
      from 1 in 32 (NT, 2.2 mm) to 1 in 189 (NT, 1.8 mm) and in the fetus of a 20-year
      old with an NT of 3.0 mm these ranged from 1 in 102 (NT, 3.2 mm) to 1 in 160 (NT,
      2.7 mm). CONCLUSIONS: We have described the effect of machine-probe combinations
      on small but very precise ultrasound measurements. Such machine-probe
      combinations led to greater variability than those ascribed to intraobserver
      differences, and significantly affected the screening risk for the same fixed
      measurement. This finding has implications for Down syndrome screening algorithms
      and audit of ultrasound operators. Furthermore, most ultrasound machines are
      neither calibrated nor specified for measurements of tenths of a mm.

PMID- 24448755
TI  - Syntheses of asymmetric zinc phthalocyanines as sensitizer of Pt-loaded graphitic
      carbon nitride for efficient visible/near-IR-light-driven H2 production.
AB  - Zinc phthalocyanine (ZnPc) derivatives with asymmetric (Zn-tri-PcNc-2) or
      symmetric (Zn-tetrad-Nc) structure, which possess wide spectral response in the
      visible/near-IR light region, are synthesized and utilized as a sensitizer of
      graphitic carbon nitride (g-C3N4) with 0.5 wt% Pt-loading for photocatalytic H2
      production. The experimental results indicate that Zn-tri-PcNc-2 exhibits much
      better photosensitization on g-C3N4 than Zn-tetrad-Nc under visible/near-IR light
      although Zn-tetrad-Nc possesses wider and stronger optical absorption property
      than Zn-tri-PcNc-2. Zn-tri-PcNc-2-Pt/g-C3N4 exhibits an average H2 production
      rate of 132 MUmol h(-1), which is much better than that (26.1 MUmol h(-1)) of Zn
      tetrad-Nc-Pt/g-C3N4 under visible-light (lambda >= 500 nm) irradiation. Moreover,
      Zn-tri-PcNc-2-Pt/g-C3N4 also shows much higher apparent quantum yield (AQY) than
      Zn-tetrad-Nc-Pt/g-C3N4 under red/near-IR light irradiation. Especially, Zn-tri
      PcNc-2-Pt/g-C3N4 exhibits impressively higher AQY (1.07%) than that (0.22%) of
      the Zn-tetrad-Nc-Pt/g-C3N4 under 700 nm monochromatic light irradiation. The much
      better photoactivity of Zn-tri-PcNc-2-Pt/g-C3N4 than Zn-tetrad-Nc-Pt/g-C3N4 is
      caused by the asymmetric structure of Zn-tri-PcNc-2, which can result in the
      electronic orbital directionality of its excited state, much faster
      photogenerated electron transfer to g-C3N4, and higher red/near-IR light
      utilization efficiency as compared to Zn-tetrad-Nc-Pt/g-C3N4. The present results
      provide an important insight into the effects of molecular structure and optical
      absorption property of phthalocyanine derivatives on the photoactivity of the dye
      sensitized semiconductor, and also guide us to further improve the solar energy
      conversion efficiency by optimizing the molecular structure and effectively
      utilizing the visible/near-IR light of sunlight. 

PMID- 24448756
TI  - Comparison between short- and long-acting erythropoiesis-stimulating agents in
      hemodialysis patients: target hemoglobin, variability, and outcome.
AB  - PURPOSE: Maintaining target hemoglobin (Hb) with minimal variability is a
      challenge in hemodialysis (HD) patients. The aim of this study is to compare the
      long- and short-acting erythropoietin-stimulating agents such as Aranesp and
      Eprex in achieving these targets. METHODS: Randomized, prospective, open-labeled
      study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on
      Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp
      group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by
      using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2
      weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target
      was set at (105-125 g/l). Primary end points were percentage of patients
      achieving target Hb, hemoglobin variability, and number of dose changes in each
      group. RESULTS: This study consisted of 139 HD patients: 72 in the Aranesp and 67
      in the Eprex-mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were
      diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p
      = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean
      number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex
      (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the
      Eprex (p < 0.001). There was no difference in hospitalization and death number
      between the 2 groups. CONCLUSIONS: Aranesp Q weekly or every 2 weeks is more
      efficient in achieving target Hb, with less dose changes and minor vascular
      access complications.

PMID- 24448757
TI  - Evaluation of the protective effect of Cystone against cisplatin-induced
      nephrotoxicity in cancer patients, and its influence on cisplatin antitumor
      activity.
AB  - PURPOSE: Evaluating the role of cystone, a polyherbal preparation, in protecting
      cancer patients against cisplatin-induced nephrotoxicity, and its impact on the
      cytotoxic activity of cisplatin. METHODS: A prospective open-label randomized
      controlled trial conducted on 49 cancer patients who received six cycles of 70
      mg/m(2) cisplatin-based regimens. The study comprised two groups, a control group
      (A) in which 28 patients received cisplatin without cystone supplement, and an
      experimental group (B) in which 21 patients received cisplatin with cystone
      supplement. Renal function parameters including serum creatinine, creatinine
      clearance, blood urea, and serum cystatin C were compared between both groups
      throughout chemotherapy cycles. Patient response to treatment was evaluated in
      both groups after 3rd and 6th cycles. RESULTS: At the end of the study, mean
      levels of serum creatinine, blood urea, and serum cystatin C were significantly
      lower, whereas creatinine clearance was significantly higher in group (B)
      compared with group (A). In group (B), there was no significant difference
      between mean levels of renal markers at baseline and after completion of
      treatment; while significant changes were observed in group (A). Grading of acute
      kidney injury according to Common Terminology Criteria for Adverse Events
      revealed significantly better renal status among patients in group (B) "grades 0
      and 1 in 76 and 24 % of the patients, respectively" compared with group (A)
      "grades 0, 1, and 2 in 36, 32, and 32 % of the patients, respectively". Based on
      Response Evaluation Criteria in Solid Tumors, there was no significant difference
      between both groups. CONCLUSIONS: Cystone can protect cancer patients from
      cisplatin nephrotoxicity without interfering with its antitumor activity.

PMID- 24448758
TI  - Accounting for trends in health poverty: a decomposition analysis for Britain,
      1991-2008.
AB  - We use data from the British Household Panel Survey to analyse changes in poverty
      of self-reported health from 1991 to 2008. We use the indices recently introduced
      by Bennett and Hatzimasoura (Poverty measurement with ordinal data. Institute for
      International Economic Policy, IIEP-WP-2011-14, 2011), which can be interpreted
      as ordinal counterparts of the classical Foster et al. (Econometrica 52(3):761
      766, 1984) poverty measures. We decompose changes in self-reported health poverty
      over time into within-group health poverty changes and population shifts between
      groups. We also provide statistical inference for the Bennett and Hatzimasoura's
      (Poverty measurement with ordinal data. Institute for International Economic
      Policy, IIEP-WP-2011-14, 2011) indices. Results suggest that when "fair" self
      reported health status is chosen as a health poverty threshold all of the used
      indices indicate the growth of health poverty in Britain. However, when the
      health poverty threshold is lower ("poor" self-reported health status) the
      increase in health poverty incidence was compensated by decreasing average health
      poverty depth and improving health inequality among those who are poor with
      respect to health. The subgroup decompositions suggest that the most important
      factors accounting for the changes in total health poverty in Britain include a
      rise of both health poverty and population shares of persons cohabiting and
      couples with no children as well as an increase of the population of retired
      persons. 

PMID- 24448759
TI  - Refinement.
AB  - The ultimate goal of the Three Rs is the full replacement of animals used in
      biomedical research and testing. However, replacement is unlikely to occur in the
      near future; therefore the scientific community as a whole must continue to
      devote considerable effort to ensure optimal animal welfare for the benefit of
      the science and the animals, i.e., the R of refinement. Laws governing the care
      and use of laboratory animals have recently been revised in Europe and the US and
      these place greater emphasis on promoting the well-being of the animals in
      addition to minimizing pain and distress. Social housing for social species is
      now the default condition, which can present a challenge in certain experimental
      settings and for certain species. The practice of positive reinforcement training
      of laboratory animals, particularly non-human primates, is gathering momentum but
      is not yet universally employed. Enhanced consideration of refinement extends to
      rodents, particularly mice, whose use is still increasing as more genetically
      modified models are generated. The wastage of extraneous mice and the method of
      their euthanasia are refinement issues that still need to be addressed. An
      international, concerted effort into defining the needs of laboratory animals is
      still necessary to improve the quality of the animal models used as well as their
      welfare.

PMID- 24448760
TI  - Novel strategies for toxicological risk assessments.

PMID- 24448761
TI  - Toxicology and stem cells: New frontiers.

PMID- 24448762
TI  - Making Fe(BPBP)-catalyzed C-H and C[double bond, length as m-dash]C oxidations
      more affordable.
AB  - The limited availability of catalytic reaction components may represent a major
      hurdle for the practical application of many catalytic procedures in organic
      synthesis. In this work, we demonstrate that the mixture of isomeric iron
      complexes [Fe(OTf)2(mix-BPBP)] (mix-1), composed of Lambda-alpha-[Fe(OTf)2(S,S
      BPBP)] (S,S-1), Delta-alpha-[Fe(OTf)2(R,R-BPBP)] (R,R-1) and Delta/Lambda-beta
      [Fe(OTf)2(R,S-BPBP)] (R,S-1), is a practical catalyst for the preparative
      oxidation of various aliphatic compounds including model hydrocarbons and
      optically pure natural products using hydrogen peroxide as an oxidant. Among the
      species present in mix-1, S,S-1 and R,R-1 are catalytically active, act
      independently and represent ca. 75% of mix-1. The remaining 25% of mix-1 is
      represented by mesomeric R,S-1 which nominally plays a spectator role in both C-H
      and C[double bond, length as m-dash]C bond oxidation reactions. Overall, this
      mixture of iron complexes displays the same catalytic profile as its enantiopure
      components that have been previously used separately in sp(3) C-H oxidations. In
      contrast to them, mix-1 is readily available on a multi-gram scale via two high
      yielding steps from crude dl/meso-2,2'-bipyrrolidine. Next to its use in C-H
      oxidation, mix-1 is active in chemospecific epoxidation reactions, which has
      allowed us to develop a practical catalytic protocol for the synthesis of
      epoxides.

PMID- 24448763
TI  - Controlling the stream of thought: working memory capacity predicts adjustment of
      mind-wandering to situational demands.
AB  - Although engaging in task-unrelated thoughts can be enjoyable and functional
      under certain circumstances, allowing one's mind to wander off-task will come at
      a cost to performance in many situations. Given that task-unrelated thoughts need
      to be blocked out when the current task requires full attention, it has been
      argued that cognitive control is necessary to prevent mind-wandering from
      becoming maladaptive. Extending this idea, we exposed participants to tasks of
      different demands and assessed mind-wandering via thought probes. Employing a
      latent-change model, we found mind-wandering to be adjusted to current task
      demands. As hypothesized, the degree of adjustment was predicted by working
      memory capacity, indicating that participants with higher working memory capacity
      were more flexible in their coordination of on- and off-task thoughts. Notably,
      the better the adjustment, the smaller performance decrements due to increased
      task demands were. On the basis of these findings, we argue that cognitive
      control does not simply allow blocking out task-unrelated thoughts but, rather,
      allows one to flexibly adjust mind-wandering to situational demands. 

PMID- 24448764
TI  - Reducing the illusion of control when an action is followed by an undesired
      outcome.
AB  - The illusion of control is the belief that our behavior produces an effect that
      is actually independent from it. This illusion is often at the core of
      superstitious and pseudoscientific thinking. Although recent research has
      proposed several evidence-based strategies that can be used to reduce the
      illusion, the majority of these experiments have involved positive illusions-that
      is, those in which the potential outcomes are desired (e.g., recovery from
      illness or earning points). By contrast, many real-life superstitions and
      pseudosciences are tied to negative illusions-that is, those in which the
      potential consequences are undesired. Examples are walking under a ladder,
      breaking a mirror, or sitting in row 13, all of which are supposed to generate
      bad luck. Thus, the question is whether the available evidence on how to reduce
      positive illusions would also apply to situations in which the outcomes are
      undesired. We conducted an experiment in which participants were exposed to
      undesired outcomes that occurred independently of their behavior. One strategy
      that has been shown to reduce positive illusions consists of warning people that
      the outcomes might have alternative causes, other than the participants' actions,
      and telling them that the best they can do to find out whether an alternative
      cause is at work is to act on only about 50% of the trials. When we gave our
      participants this information in an experiment in which the outcomes were
      undesired, their illusion was enhanced rather than reduced, contrary to what
      happens when the outcome is desired. This suggests that the strategies that
      reduce positive illusions may work in just the opposite way when the outcome is
      undesired.

PMID- 24448765
TI  - Effects of non-toxic cryoprotective agents on the viability of cord blood derived
      MNCs.
AB  - The present work investigates the effects of a variety of natural cryoprotectants
      in combination on post-thaw viability and apoptosis of cryopreserved mononuclear
      cells (MNCs) derived from umbilical cord blood. The extracellular cryoprotectants
      (10 mM) namely trehalose, hydroxyl ethyl starch, polyvinyl pyrrolidine and
      intracellular CPAs (5 mM) like erythritol, taurine and ectoine were used to
      prepare different combinations of freezing medium following L9 (3(4)) Taguchi
      orthogonal array. Catalase, coenzyme Q10 and n-acetyl cystine (100 microg/m) were
      added as antioxidants. Among various combinations, freezing medium consisting of
      hydroxyl ethyl starch, ectoin and co-enzyme Q10 with 10% FBS is found to be most
      effective combination achieving maximum cell viability of 93%, 5.6% early
      apoptotic, 0.7% late apoptotic and 0.1% necrotic cells. SEM and phase contrast
      microscopy confirmed the normal cell morphology of the post-thaw cultured cells
      with retaining their membrane integrity. The survival rate of MNCs is higher than
      the rate achieved using conventional Me2SO.

PMID- 24448766
TI  - Is sucrose required in open pulled straw (OPS) vitrification of mouse embryos?
AB  - The study addresses the relevance of sucrose with OPS vitrification of murine
      blastocysts. In a 3 x 3 factorial experiment, blastocysts were subjected to
      vitrification solution (20% Me2SO and 20% EG) containing 0.0, 0.4 or 0.8M sucrose
      and warming solution (HEPES buffered TCM 199) containing 0.00, 0.25 or 0.50M
      sucrose. After 48h of in vitro culture, with 0.4 M sucrose in vitrification
      solution, 84-87% of embryos had reached the expanded blastocyst stage, as
      compared to 76-82% with 0.0M and 40-54% (P < 0.01) with 0.8M sucrose. Hatching
      rates confirmed the tendency. The sucrose content of the warming solution had no
      significant effect on expansion or hatching rates (P > 0.05). It may be concluded
      that, whereas, vitrification solution should contain a moderate concentration of
      sucrose, in dilution medium sucrose is dispensable. This implies that embryos may
      be transferred directly after warming, which, if applicable to farm animals,
      would greatly facilitate vitrification in practice.

PMID- 24448767
TI  - Vitrification of human umbilical cord Wharton's jelly-derived mesenchymal stem
      cells.
AB  - The aim of this study was to evaluate whether vitrification is an effective
      cryopreservation method for storage of human umbilical cord mesenchymal cells
      (HUCMs). HUCMs were vitrified using a two step method. The viability of vitrified
      HUCMs (v-HUCM) and non-vitrified HUCMs (n-HUCM) was determined by Trypan Blue
      staining. The expression of several markers was evaluated using flow cytometry.
      The osteogenic, adipogenic and chondrogenic differentiation potential of v-HUCMs
      and n-HUCMs was determined. The post-warming viability of HUCMs was 95.54 +/-
      2.30. The expression of surface antigens (strong positive for CD44, CD90 and
      CD105; negative for CD34 and CD45) was similar in the above mentioned groups. The
      v-HUCM cells retained ability to differentiate into osteoblasts, adipocytes and
      chondrocytes under appropriate culture conditions. The analysis of these results
      showed that vitrification is a reliable and effective method for cryopreservation
      of human umbilical cord mesenchymal cells.

PMID- 24448768
TI  - Medium- and long-term storage of the Pycnanthemum (mountain mint) germplasm
      collection.
AB  - The United States of America collection of mountain mint (Pycnanthemum Michx.) is
      held at the USDA-ARS National Clonal Germplasm Repository (NCGR) in Corvallis,
      Oregon as seed, potted plants and tissue cultures and a long-term storage
      collection is preserved at the USDA-ARS National Center for Genetic Resources
      Preservation (NCGRP) in Fort Collins, Colorado. The clonal collection is
      comprised of 34 accessions as potted plants that are duplicated with 31
      accessions stored as in vitro cultures at 4 degrees C in tissue culture bags for
      medium-term storage at NCGR and as cryopreserved shoot tips in liquid nitrogen at
      NCGRP for long-term storage. This study reports on these two models of
      preservation of mountain mint at the U.S. National Plant Germplasm System. In
      vitro plants required 2 to 7 months for propagation on MS medium without growth
      regulators before storage at 4 degrees C. Plants remained in storage with good
      vigour in bags on 1/2x nitrogen MS medium without growth regulators for a mean of
      2.08 y. An encapsulation-dehydration protocol was successful for cryopreservation
      of shoot tips from cold acclimated in vitro plants. Post-cryo viability,
      indicated by shoot tips with developed leaves and roots, ranged from 60 to 100 %
      for 27 accessions and 40 to 50 % for the other four. The encapsulation
      dehydration cryopreservation method proved suitable for long-term preservation of
      the 31 Pycnanthemum accessions. These alternative storage forms allow for active
      use of the collection as well as base storage for clonally propagated accessions.

PMID- 24448769
TI  - Cryopreservation of Neottopteris nidus prothallus and green globular bodies by
      droplet-vitrification.
AB  - Neottopteris nidus prothalli and green globular bodies (GGBs) were successfully
      cryopreserved by droplet-vitrification. Prothalli were subjected to different
      treatments. The following parameters were studied: the age of in vitro mother
      plants from which prothalli were originated (30 to 90-day old), length of
      exposure to loading solution (LS) (20 to 40 min) and length of exposure to the
      plant vitrification solution (PVS2) (10 to 55 min). N. nidus GGBs and GGBs in
      suspension were subjected to PVS2 for 20, 30 and 40 min before liquid nitrogen
      exposure. The highest prothalli regrowth (92%) occurred when they were exposed
      for 40 min to LS, followed by 20 min to PVS2 and when they originated from non
      preconditioned 45-day old mother plants. The highest GGB (100%) and GGB
      suspension regrowth (100%) after cryopreservation occurred when they were exposed
      to PVS2 for either 20 min or 40 min.

PMID- 24448770
TI  - Establishment and cryopreservation of a skin fibroblast cell line derived from
      Yunnan semi-fine wool sheep in the presence of synthetic ice blocker.
AB  - In this study, the fibroblasts cell line derived from ear marginal tissue of
      Yunnan semi-fine wool sheep was successfully established using the primary
      explants technique and cryopreservation technology. Additionally, the protective
      effect of synthetic ice blocker (SIB) including 1, 3-cyclohexanediol (1, 3-CHD)
      and 1, 4-cyclohexanediol (1, 4-CHD) on frozen fibroblast cells was also assessed
      and compared. Propidium iodide (PI) was used to stain the dead cells following
      cryopreservation and thawing. The results showed that compared with Medium 199
      (M199) and Dulbecco's modified Eagle's medium : Nutrient Mixture F-12 (1 : 1)
      Mixture (DMEM/F12), Dulbecco's modified Eagle's medium (DMEM) may be more
      suitable for the primary culture of fibroblast cells of Yunnan semi-fine wool
      sheep. The growth curve of cells is a typical "S" type. After subculture for four
      days, the cells entered the plateau phase and began to degenerate. Biological
      analysis showed that the population doubling time (PDT) for subculturing
      fibroblast cells was approximately 26h. The Karyotyping data indicated that the
      percentage of fibroblast cells with normal chromosome number 2n = 54 was over 90%
      following subculture for 10 passages. Moreover, the tests for bacteria, fungi,
      viruses and mycoplasma were negative. After serial subculture for 5 generations,
      the fibroblast cells were cryopreserved in the presence or absence of 1, 3-CHD or
      1, 4-CHD. The data indicated that with increase of the synthetic ice blocker
      concentrations, the viability of frozen-thawed fibroblast cells was firstly
      increased and then decreased. When the concentration of 1, 3-CHD or 1, 4-CHD was
      50 mM, the viable percentage of frozen-thawed fibroblast cells was 91.93% +/-
      2.24% and 94.13% +/- 0.55% respectively and significantly higher than that of the
      cells frozen in the absence of synthetic ice blockers (88.10% +/- 1.49%, P <
      0.05). In conclusion, the skin fibroblast cell line of Yunnan semi-fine wool
      sheep was firstly established in this study. Additionally, the presence of
      synthetic ice blocker can increase the viability of frozen-thawed sheep
      fibroblast cell line.

PMID- 24448771
TI  - Development of cryopreservation for Loxocarya cinerea---an endemic Australian
      plant species important for post-mining restoration.
AB  - We report the development of a cryopreservation protocol for the endemic Western
      Australian plant species Loxocarya cinerea (Restionaceae). Shoot tips from two
      genotypes, SXH404 and SXH804, were cryopreserved using the droplet-vitrification
      technique. Control explants, which were cryoprotected, but not cooled, showed
      regeneration for both genotypes (SXH404, 22.1 +/- 5.9%; SXH804, 67.7 +/- 9.6%).
      Extension of incubation in PVS2 from 30 to 60 min did not lead to survival after
      cryopreservation. Thermal analysis using differential scanning calorimetry
      confirmed the beneficial effect of a loading phase but also revealed no or very
      little ice formation after cryoprotection of shoot tips in other treatments.
      Regeneration following cryopreservation was obtained for genotype SXH804 (4.3 +/-
      2.1%) but not for SXH404. Regenerated explants of L. cinerea SXH804 were
      morphologically identical to tissue-cultured plants. As an alternative to shoot
      tips, callus tissues of clone SXH404 were successfully cryopreserved (> 66.7%
      post LN survival) using the same protocol.

PMID- 24448772
TI  - In vitro culture thawed human ovarian tissue: NIV versus slow freezing method.
AB  - The aim of this study was to determine if the needle immersed vitrification
      method (NIV) can improve the growth potential of thawed ovarian tissue in vitro
      culture. Human ovarian cortical tissues were cryopreserved using NIV and slow
      freezing method. After 14 days of culture, the preservation outcomes of NIV and
      slow freezing groups were analyzed histologically using light microscope and
      apoptosis was assessed by TUNEL assay. The result showed that the percentage of
      morphologically abnormal primordial follicles was lower in NIV group than in slow
      freezing group (P < 0.05). The incidence of TUNEL-positive primordial follicles
      was lower in NIV group than in slow freezing group (P < 0.05). The study showed
      that cryopreservation of human ovarian tissue with NIV was effective in improving
      the growth potential of frozen-thawed ovarian tissue in vitro culture.

PMID- 24448773
TI  - The relation between cryoprotective and physicochemical properties of
      oxyethylated methyl cellosolve-based media.
AB  - Oxyethyl derivatives of polyol class members such as glycerol and ethylene glycol
      with various polymerization degrees possess low toxicity and cryoprotective
      properties via an exocellular mechanism. To develop the cryoprotective media
      based on non-penetrating cryoprotectants, we studied cryoprotective and physico
      chemical properties of oxyethylated methyl cellosolve (OEMC)-based media. Media
      containing 20% and 30% OEMC were prepared with 50 mmol/l and 150 mmol/l NaCl. In
      some media, NaCl content was reduced, and sucrose, mannitol or glucose was added
      to attain the isotonic media. Cryopreservation of red blood cells depends on the
      media composition and physico-chemical properties. The increases in dynamic
      viscosity due to higher OEMC concentration and in ionic strength resulted from
      higher NaCl concentration lead to greater erythrocytes dehydration prior to
      freezing, and lower red blood cell preservation upon freezing. Salt substitution
      with carbohydrates in 20% OEMC media reduces ionic strength and increases OEMC
      distribution coefficient. The correlation of red blood cell protection upon
      freezing is discussed in terms of the media physico-chemical properties (ionic
      strength, viscosity and surface tension), cryoprotectant distribution
      coefficient, and cell dehydration.

PMID- 24448774
TI  - Human spermatozoa cryopreservation: comparison of three different freezing
      protocols.
AB  - Human spermatozoa cryopreservation has significantly improved over the last few
      decades, but the actual protocols are neither optimal nor standardized between
      different laboratories in spite of the importance of preserving male fertility or
      treating severely infertile males. In the present study we aimed to determine the
      best in-house method of rapid freezing in terms of sperm motility and vitality by
      comparing three different rapid methods of human spermatozoa cryopreservation.
      Our data showed that M1 (triphasic cooling) is the method associated with a
      significantly lower deterioration of semen quality in comparison with mono or
      biphasic cooling. Differences observed among the three protocols were supported
      by statistical analysis. These data reinforce previous evidences about the
      influence of sperm quality on IVF outcome and suggest the importance of improving
      sperm cryopreservation techniques especially when semen is seriously compromised
      at baseline.

PMID- 24448775
TI  - Influence of pectins on NADPH oxidase and phagocytic activity of neutrophils
      during cryopreservation.
AB  - NADPH oxidase activation was studied by detecting the reactive oxygen species
      (ROS) and the dynamics of neutrophil phagocytic activity in blood before freezing
      and one day after exposure to -20 degrees C in the presence of pectic
      polysaccharides. Pectins (excluding lemnan) were found to increase the phagocytic
      activity of neutrophils, promote the formation of ROS in these cells and enhance
      NADPH oxidase activity in the following order: bergenan, comaruman, lemnan,
      apiuman, and potamogetonan. Cryoprotective action of lemnan and comaruman was
      proposed to be related to their unique chemical structures.

PMID- 24448776
TI  - Excess risk of hip fractures attributable to the use of antidepressants in five
      European countries and the USA.
AB  - SUMMARY: The association between antidepressant use and hip fracture remains
      unclear. We conducted a systematic review to estimate Population Attributable
      Risks (PAR) for France, Germany, Italy, Spain, UK, and the USA. We report a
      heterogeneous prevalence of antidepressant use and related PARs, both lowest for
      Italy and highest for the USA. INTRODUCTION: Antidepressant use has been
      associated with an increased hip fracture risk in observational studies. However,
      the potential contribution of antidepressant consumption on the population rate
      of hip fractures has not been described. Our aim was to estimate the impact of
      the use of different classes of antidepressants on the rate of hip fracture at a
      population-level in France, Germany, Italy, Spain, the UK, and the USA. METHODS:
      We conducted a systematic literature review to estimate the pooled relative risk
      (RR) of hip fracture according to use of antidepressants. Prevalence rates of
      antidepressant use (Pe) in 2009 were calculated for each country using the The
      Intercontinental Medical Statistics database and three public databases from
      Denmark, the Netherlands, and Norway. Both the RR and Pe were used to calculate
      PAR of hip fractures associated with antidepressant use. RESULTS: The literature
      review showed an increased risk of hip fractures in antidepressant users (RR,
      1.7; 95 % confidence interval (CI), 1.5-2.0). Rates of antidepressant use showed
      considerable differences between countries, ranging from 4.4 % (Italy) to 11.2 %
      (USA) in the year 2009. The estimated PAR of antidepressants on hip fracture
      rates were 3.0 % (95 % CI, 2.0-4.1; Italy), 3.1 % (95 % CI, 2.1-4.3; Germany),
      3.8 % (95 % CI, 2.6-5.3; France), 4.8 % (95 % CI, 3.3-6.5; Spain), 4.9 % (95 %
      CI, 3.4-6.8; UK), and 7.2 % (95 % CI, 5.0-9.9; USA). PARs differed for different
      types of antidepressants, with highest attributable risks for selective serotonin
      reuptake inhibitors. CONCLUSIONS: These findings suggest that the potential
      contribution of antidepressant use to the population rate of hip fractures in the
      five large EU countries and the USA varies between 3 and 7 %.

PMID- 24448777
TI  - A new mathematical model to simulate AVA cold-induced vasodilation reaction to
      local cooling.
AB  - The purpose of this work was to integrate a new mathematical model with a bioheat
      model, based on physiology and first principles, to predict thermoregulatory
      arterio-venous anastomoses (AVA) and cold-induced vasodilation (CIVD) reaction to
      local cooling. The transient energy balance equations of body segments
      constrained by thermoregulatory controls were solved numerically to predict
      segmental core and skin temperatures, and arterial blood flow for given metabolic
      rate and environmental conditions. Two similar AVA-CIVD mechanisms were
      incorporated. The first was activated during drop in local skin temperature (<32 
      degrees C). The second mechanism was activated at a minimum finger skin
      temperature, T(CIVD, min), where the AVA flow is dilated and constricted once the
      skin temperature reached a maximum value. The value of T(CIVD,min) was determined
      empirically from values reported in literature for hand immersions in cold fluid.
      When compared with published data, the model predicted accurately the onset time
      of CIVD at 25 min and T(CIVD,min) at 10  degrees C for hand exposure to still air
      at 0  degrees C. Good agreement was also obtained between predicted finger skin
      temperature and experimentally published values for repeated immersion in cold
      water at environmental conditions of 30, 25, and 20  degrees C. The CIVD thermal
      response was found related to core body temperature, finger skin temperature, and
      initial finger sensible heat loss rate upon exposure to cold fluid. The model
      captured central and local stimulations of the CIVD and accommodated observed
      variability reported in literature of onset time of CIVD reaction and
      T(CIVD,min).

PMID- 24448779
TI  - Mitochondrial DNA copy numbers in pyramidal neurons are decreased and
      mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer's
      disease hippocampi.
AB  - Alzheimer's disease (AD) is the major cause of adult-onset dementia and is
      characterized in its pre-diagnostic stage by reduced cerebral cortical glucose
      metabolism and in later stages by reduced cortical oxygen uptake, implying
      reduced mitochondrial respiration. Using quantitative PCR we determined the
      mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20
      pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using
      laser capture microdissection, and the relative expression of mitochondrial
      biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL)
      cases. AD pyramidal but not dentate granule neurons had significantly reduced
      mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers
      in CTL, but not AD, positively correlated with cDNA levels of multiple
      mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1alpha
      were positively correlated with multiple downstream mitobiogenesis factors.
      Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with
      hippocampal Abeta1-42 levels. After 48 h exposure of H9 human neural stem cells
      to the neurotoxic fragment Abeta25-35, mtDNA copy numbers were not significantly
      altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced
      mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are
      disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex
      alterations of mitochondria-host cell relationships in AD. 

PMID- 24448780
TI  - Predictors of institutionalization in dementia: a three year longitudinal study.
AB  - Patients with dementia often require institutionalization when they can no longer
      care for themselves. The study examined demographic and clinical variables that
      predict the time until institutionalization in patients with dementia attending
      memory clinics. Of 970 patients recruited from nine memory clinics around
      Australia, 779 patients had dementia at baseline. Measures of dementia severity,
      cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and
      medication use were completed for all patients. Patients were followed for three
      years. Overall, 197 (25.3%) of the patients with dementia were institutionalized
      within three years. Lower cognitive ability, lower functional ability, and more
      neuropsychiatric symptoms at baseline predicted a shorter time until
      institutionalization, as did use of antipsychotic medication. In addition,
      greater deterioration in cognitive ability, functional ability, and
      neuropsychiatric symptoms over the initial three months predicted a shorter time
      to institutionalization. The findings confirm that clinical features of dementia
      at baseline predict the time to institutionalization, as do greater changes in
      symptoms over three months independent of baseline levels. 

PMID- 24448781
TI  - Concentrations of matrix metalloproteinases and their tissue inhibitors in the
      cerebrospinal fluid of patients with Alzheimer's disease.
AB  - BACKGROUND: A growing body of evidence shows the involvement of matrix
      metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in
      neurodegeneration processes, but reports of their concentrations in the
      cerebrospinal fluid (CSF) are inconsistent. OBJECTIVE: Therefore, the aim of our
      study was to evaluate the CSF concentrations of MMP-2, MMP-3, MMP-9, and their
      inhibitors (TIMP-1 and TIMP-2) in carefully selected groups of patients with
      Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented
      controls, whose clinical and neuropsychological diagnoses were confirmed by the
      corresponding CSF biomarkers of neurochemical dementia diagnostics: decreased
      concentrations of Abeta1-42 and/or Abeta42/40 ratio, and increased concentrations
      of Tau and pTau181 proteins. METHODS: The study included 33 AD patients, 15
      subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF
      concentrations of MMPs and TIMPs were determined with ELISAs. RESULTS: CSF
      concentrations of MMP-9 were significantly lower, and the concentrations of MMP-3
      significantly higher in AD patients compared to the controls. Neither MMP-2 nor
      TIMPs showed significant changes among the groups investigated. CONCLUSION:
      Altered concentrations of two out of three MMPs investigated in this study
      suggest that this family of biomolecules may play a role in the AD
      pathophysiology. Further studies are needed to establish their potential
      diagnostic utility.

PMID- 24448782
TI  - Losartan-induced hypotension leads to tau hyperphosphorylation and memory
      deficit.
AB  - Recent studies have reported a correlation between dementia and low blood
      pressure. How hypotension is associated with the increased risk of Alzheimer's
      disease (AD) remains unclear. Here we show that one month treatment of losartan,
      an angiotensin II type 1 (AT1) receptor antagonist, causes chronic and sustained
      hypotension, along with oxidative stress in adult male Sprague-Dawley rats.
      Furthermore, we show that losartan treatment increases the level of inactivated
      protein phosphatase 2A (PP2A) and the hyperphosphorylation of tau at Ser 199 and
      Ser 396. Rats treated with losartan present memory deficits and decreases in
      spine-density. These findings suggest that losartan-induced hypotension may
      increase the risk of AD-like pathological alteration and behavioral impairment
      through oxidative stress which leads to tau hyperphosphorylation and loss of
      dendritic spines. 

PMID- 24448783
TI  - Visuo-perceptive priming in Alzheimer's disease: evidence for a multi
      componential implicit memory system.
AB  - In the past two decades research has highlighted how implicit memory processes
      are spared in degenerative disorders, such as Alzheimer's disease (AD), which are
      characterized by the early onset of explicit memory deficits. However, according
      to recent studies, there may be dissociations among different types of implicit
      memory. Although several studies have shown selective sparing of lexical priming
      in AD, it is not completely clear what happens to other types of implicit memory
      processes, such as visuo-perceptual priming. The present study examines the
      possibility that the visuo-perceptual priming effect is spared in AD. We tested
      two groups of participants, i.e., a group of AD patients and a group of healthy
      age-matched controls, using a visuo-perceptual priming task. The task required
      the identification of fragmented pictures. Results showed a deficient priming
      effect in AD patients when it was measured by an Identification of Fragmented
      Pictures task. We discuss our results in light of the current hypothesis of a
      functional segregation in priming processes. 

PMID- 24448784
TI  - Structural and functional brain changes in middle-aged type 2 diabetic patients:
      a cross-sectional study.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is an emerging risk factor for
      cognitive impairment. Whether this impairment is a direct effect of this
      metabolic disorder on brain function, a consequence of vascular disease, or both,
      remains unknown. Structural and functional neuroimaging studies in patients with
      T2DM could help to elucidate this question. OBJECTIVE: We designed a cross
      sectional study comparing 25 T2DM patients with 25 age- and gender-matched
      healthy control participants. Clinical information, APOE genotype, lipid and
      glucose analysis, structural cerebral magnetic resonance imaging including voxel
      based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were
      obtained in all subjects. METHODS: Gray matter densities and metabolic
      differences between groups were analyzed using statistical parametric mapping. In
      addition to comparing the neuroimaging profiles of both groups, we correlated
      neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance
      measurement (HOMA-IR) in the diabetic patients group. RESULTS: Patients with T2DM
      presented reduced gray matter densities and reduced cerebral glucose metabolism
      in several fronto-temporal brain regions after controlling for various vascular
      risk factors. Furthermore, within the T2DM group, longer disease duration, and
      higher HbA1c levels and HOMA-IR were associated with lower gray matter density
      and reduced cerebral glucose metabolism in fronto-temporal regions. CONCLUSION:
      In agreement with previous reports, our findings indicate that T2DM leads to
      structural and metabolic abnormalities in fronto-temporal areas. Furthermore,
      they suggest that these abnormalities are not entirely explained by the role of
      T2DM as a cardiovascular risk factor.

PMID- 24448785
TI  - Altered function of hippocampal CA1 pyramidal neurons in the rTg4510 mouse model
      of tauopathy.
AB  - The formation of neurofibrillary tangles from the assembly of hyperphosphorylated
      tau leads to dendritic and axonal instability, synaptic degeneration, and
      neuronal loss. To understand the early physiological consequences of aberrant tau
      expression, we characterized the physiology of CA1 pyramidal neurons in rTg4510
      female mice and non-transgenic (wt) littermate controls. We studied mice at the
      age of 10-12 weeks where only minimal hyperphosphorylated pretangle tau was
      present, and 22-24 weeks old mice with significant neurofibrillary tangle
      pathology. Our electrophysiological analysis included input-output relation,
      paired-pulse facilitation, and whole cell patch-clamp recordings of neurons to
      measure action potential threshold and action potential properties, chord
      conductance, and characterization of AMPA receptor mediated synaptic
      transmission. We found that the input-output relation in field (excitatory
      postsynaptic potentials, EPSP) and whole cell recordings (excitatory postsynaptic
      currents, EPSC) were impaired in rTg4510 mice compared to wt controls at both
      ages. We measured a diminished tail current charge after depolarizing voltage
      input in rTg4510 mice compared to wt in both young and aged mice. Additionally,
      mini-EPSC properties (peak and decay time) were essentially similar between
      genotypes and age groups investigated. Surprisingly, in the 22-24 week old group,
      the mini-EPSC frequency was significantly increased (interevent interval 0.8 +/-
      0.1 in wt compared to 0.3 +/- 0.1 in rTg4510 mice). These data indicate that the
      developmentally regulated expression of human P301L tau in CA1 pyramidal neurons
      coincide with changes in neuronal excitability but also that significant
      presynaptic changes occur late during the progression of tau pathology in this
      mouse model. 

PMID- 24448786
TI  - Alzheimer's disease is associated with decreased risk of cancer-specific
      mortality: a prospective study (NEDICES).
AB  - Previous studies have shown that Alzheimer's disease (AD) is associated with a
      reduced risk of cancer. However, most studies exclude those with undiagnosed
      dementia. The only way to overcome this methodological issue is to examine all
      the participants or to screen the population for symptoms of dementia with a
      validated instrument and confirm any suspected dementia patients with a clinical
      examination (i.e., a two-phase investigation method). We used this methodology to
      estimate whether cancer-specific mortality is associated with AD and other types
      of dementia in a prospective population-based study (NEDICES) involving 5,278
      elderly people. Community-dwelling subjects with and without dementia were
      identified and followed for a median of 12.5 years, after which the death
      certificates of those who deceased were examined. A total of 1,976 (47.1%) died,
      including 277 who had possible or probable AD and 126 with non-AD dementia.
      Cancer was reported significantly less often in those with possible or probable
      AD (5.8%) or non-AD dementia (6.3%) than in those without dementia (26.5%). In an
      unadjusted Cox model, hazard ratio (HR) of cancer-specific mortality in
      participants with AD = 0.45 (p = 0.002) and HR in participants with non-AD
      dementia = 0.62 (p = 0.179) when compared to the non-demented group. In a Cox
      model that adjusted for a variety of demographic factors and co-morbidities, HRs
      of cancer-specific mortality in participants with AD = 0.50 (p = 0.028) and 0.97
      (p = 0.942) in non-AD dementia. This study provides further evidence of an
      inverse association between cancer and AD. 

PMID- 24448787
TI  - Plasma levels of HDL and carotenoids are lower in dementia patients with vascular
      comorbidities.
AB  - Elevated serum cholesterol concentrations in mid-life increase risk for
      Alzheimer's disease (AD) in later life. However, lower concentrations of
      cholesterol-carrying high density lipoprotein (HDL) and its principal
      apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports
      oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the
      hypothesis that lower HDL and oxocarotenoid concentrations during AD may render
      HDL susceptible to nitration and oxidation and in turn reduce the efficiency of
      reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples
      were obtained from subjects with (1) AD without cardiovascular comorbidities and
      risk factors (AD); (2) AD with cardiovascular comorbidities and risk factors (AD
      Plus); (3) normal cognitive function; for carotenoid determination by HPLC,
      analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to
      isolated HDL. HDL concentration in the plasma from AD Plus patients was
      significantly lower compared to AD or control subject HDL levels. Similarly,
      lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD
      Plus patients compared to those in control subjects or AD patients, and
      oxocarotenoid concentrations correlated with Mini-Mental State Examination
      scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects
      irrespective of diagnosis was equally effective at mediating RCT. HDL
      concentration is lower in AD Plus patients' plasma and thus capacity for RCT is
      compromised. In contrast, HDL from patients with AD-only was not different in
      concentration, modifications, or function from HDL of healthy age-matched donors.
      The relative importance of elevating HDL alone compared with elevating
      carotenoids alone or elevating both to reduce risk for dementia should be
      investigated in patients with early signs of dementia.

PMID- 24448788
TI  - Low levels of soluble NG2 in cerebrospinal fluid from patients with dementia with
      Lewy bodies.
AB  - The proteoglycan NG2 plays a major role in proliferation, migration, and
      differentiation of pericytes and NG2 cells in the brain. We have previously
      reported decreased soluble NG2 (sNG2) levels in cerebrospinal fluid (CSF) from
      patients with Alzheimer's disease (AD) and a relationship between sNG2 and AD
      biomarkers in these patients. To further investigate whether alterations in sNG2
      is specific to AD pathology, we measured levels of sNG2 in CSF from a patient
      cohort consisting of non-demented controls (n = 51), patients with Parkinson's
      disease (PD) (n = 61), and patients with dementia with Lewy bodies (DLB) (n =
      37), two synucleinopathies whereof the latter disorder frequently coincides with
      amyloid-beta pathology similar to AD. We found decreased sNG2 concentrations in
      DLB patients, but not in PD patients, compared to controls. Levels of sNG2 in
      controls and PD patients correlated to T-tau, P-tau, alpha-synuclein, and
      neurosin. Only one correlation, between sNG2 and neurosin, was found in DLB
      patients. Analysis of a second cohort consisting of controls (n = 23) and DLB
      patients (n = 31) showed that the result was reproducible, as lower levels of
      sNG2 again were found in DLB patients compared to controls. We conclude that
      lower levels of sNG2 levels indicate a DLB-related impact on NG2 expressing cells
      foremost associated with neuropathology linked to accumulation of amyloid-beta
      and not alpha-synuclein. 

PMID- 24448789
TI  - Accuracy of cerebrospinal fluid Abeta(1-42) for Alzheimer's disease diagnosis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia,
      accounting for 65-70% of all dementia cases. OBJECTIVE: We performed a systematic
      review and meta-analysis to estimate the accuracy of cerebrospinal fluid Abeta1
      42 for the diagnosis of AD. A comprehensive search of the Cochrane Library,
      MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published
      from January 1990 to August 2013. The following Medical Subject Headings (MeSH)
      terms were searched: "Alzheimer disease" or "AD" and "amyloid-beta" or "Abeta1
      42". METHODS: We included case-control and cross-sectional studies, prospective
      or retrospective, that evaluated Abeta1-42 levels in AD. Statistical analysis was
      performed using REVMAN 5.2, Meta Disc, and Stata 11.0. RESULTS: A total of 804
      citations were identified by the search strategy and 41 studies were included.
      Meta-analysis showed a sensitivity of 84.3% (95% CI: 85.6%-81%) and specificity
      of 79.4% (95% CI: 77.6%-81.1%). The diagnostic odds ratio was 28.9 (95% CI: 21.2
      39.5). CONCLUSION: Our study demonstrated that Abeta1-42 can discriminate AD from
      controls with good sensitivity and specificity.

PMID- 24448791
TI  - Editorial: carpal tunnel syndrome.

PMID- 24448792
TI  - Commentary on Akbar et al. Prevalence of carpal tunnel syndrome and wrist
      osteoarthritis in long-term paraplegic patients compared with controls.

PMID- 24448790
TI  - Caffeoylquinic acids in Centella asiatica protect against amyloid-beta toxicity.
AB  - The accumulation of amyloid-beta (Abeta) is a hallmark of Alzheimer's disease and
      is known to result in neurotoxicity both in vivo and in vitro. We previously
      demonstrated that treatment with the water extract of Centella asiatica (CAW)
      improves learning and memory deficits in Tg2576 mice, an animal model of Abeta
      accumulation. However the active compounds in CAW remain unknown. Here we used
      two in vitro models of Abeta toxicity to confirm this neuroprotective effect and
      identify several active constituents of the CAW extract. CAW reduced Abeta
      induced cell death and attenuated Abeta-induced changes in tau expression and
      phosphorylation in both the MC65 and SH-SY5Y neuroblastoma cell lines. We
      confirmed and quantified the presence of several mono- and dicaffeoylquinic acids
      (CQAs) in CAW using chromatographic separation coupled to mass spectrometry and
      ultraviolet spectroscopy. Multiple dicaffeoylquinic acids showed efficacy in
      protecting MC65 cells against Abeta-induced cytotoxicity. Isochlorogenic acid A
      and 1,5-dicaffeoylquinic acid were found to be the most abundant CQAs in CAW, and
      the most active in protecting MC65 cells from Abeta-induced cell death. Both
      compounds showed neuroprotective activity in MC65 and SH-SY5Y cells at
      concentrations comparable to their levels in CAW. Each compound not only
      mitigated Abeta-induced cell death, but was able to attenuate Abeta-induced
      alterations in tau expression and phosphorylation in both cell lines, as seen
      with CAW. These data suggest that CQAs are active neuroprotective components in
      CAW, and therefore are important markers for future studies on CAW
      standardization, bioavailability, and dosing. 

PMID- 24448793
TI  - Commentary on Asshein and Finsen. The DASH and the QuickDASH instruments.
      Normative values in the general population in Norway: and Iwatsuki et al.
      Comparative responsiveness of the Hand 20 and the DASH-JSSH to clinical changes
      after carpal tunnel release.

PMID- 24448794
TI  - Commentary on Zyluk et al. No correlation between sonographic and
      electrophysiological parameters in carpal tunnel syndrome; and Yalcin et al.
      Ultrasound diagnosis of ulnar neuropathy: comparison of symptomatic and
      asymtomatic nerve thickness.

PMID- 24448795
TI  - Re: del Pinal F. Editorial: I have a dream ... reflex sympathetic dystrophy (RSD
      or Complex Regional Pain Syndrome - CRPS I) does not exist. J Hand Surg Eur.
      2013, 38: 595-7.

PMID- 24448796
TI  - Re: Young K, Greenwood A, MacQuillan A, Lee S, Wilson S. Paediatric hand
      fractures. J Hand Surg Eur. 2013, 38: 898-902.

PMID- 24448797
TI  - Reply: Young K, Greenwood A, MacQuillan A, LeeS, Wilson S. Paediatric hand
      fractures. JHand Surg Eur. 2013, 8: 898-902 and Crowley B. Commentary on Young et
      al.Paediatric hand fractures. J Hand Surg Br.2013, 8: 903-4.

PMID- 24448798
TI  - Converting the yeast arginine can1 permease to a lysine permease.
AB  - Amino acid uptake in yeast cells is mediated by about 16 plasma membrane
      permeases, most of which belong to the amino acid-polyamine-organocation (APC)
      transporter family. These proteins display various substrate specificity ranges.
      For instance, the general amino acid permease Gap1 transports all amino acids,
      whereas Can1 and Lyp1 catalyze specific uptake of arginine and lysine,
      respectively. Although Can1 and Lyp1 have different narrow substrate
      specificities, they are close homologs. Here we investigated the molecular rules
      determining the substrate specificity of the H(+)-driven arginine-specific
      permease Can1. Using a Can1-Lyp1 sequence alignment as a guideline and a three
      dimensional Can1 structural model based on the crystal structure of the bacterial
      APC family arginine/agmatine antiporter, we introduced amino acid substitutions
      liable to alter Can1 substrate specificity. We show that the single substitution
      T456S results in a Can1 variant transporting lysine in addition to arginine and
      that the combined substitutions T456S and S176N convert Can1 to a Lyp1-like
      permease. Replacement of a highly conserved glutamate in the Can1 binding site
      leads to variants (E184Q and E184A) incapable of any amino acid transport,
      pointing to a potential role for this glutamate in H(+) coupling. Measurements of
      the kinetic parameters of arginine and lysine uptake by the wild-type and mutant
      Can1 permeases, together with docking calculations for each amino acid in their
      binding site, suggest a model in which residues at positions 176 and 456 confer
      substrate selectivity at the ligand-binding stage and/or in the course of
      conformational changes required for transport. 

PMID- 24448799
TI  - Transported substrate determines exchange rate in the multidrug resistance
      transporter EmrE.
AB  - EmrE, a small multidrug resistance transporter, serves as an ideal model to study
      coupling between multidrug recognition and protein function. EmrE has a single
      small binding pocket that must accommodate the full range of diverse substrates
      recognized by this transporter. We have studied a series of tetrahedral
      compounds, as well as several planar substrates, to examine multidrug recognition
      and transport by EmrE. Here we show that even within this limited series, the
      rate of interconversion between the inward- and outward-facing states of EmrE
      varies over 3 orders of magnitude. Thus, the identity of the bound substrate
      controls the rate of this critical step in the transport process. The binding
      affinity also varies over a similar range and is correlated with substrate
      hydrophobicity within the tetrahedral substrate series. Substrate identity
      influences both the ground-state and transition-state energies for the
      conformational exchange process, highlighting the coupling between substrate
      binding and transport required for alternating access antiport. 

PMID- 24448800
TI  - Doc toxin is a kinase that inactivates elongation factor Tu.
AB  - The Doc toxin from bacteriophage P1 (of the phd-doc toxin-antitoxin system) has
      served as a model for the family of Doc toxins, many of which are harbored in the
      genomes of pathogens. We have shown previously that the mode of action of this
      toxin is distinct from the majority derived from toxin-antitoxin systems: it does
      not cleave RNA; in fact P1 Doc expression leads to mRNA stabilization. However,
      the molecular triggers that lead to translation arrest are not understood. The
      presence of a Fic domain, albeit slightly altered in length and at the catalytic
      site, provided a clue to the mechanism of P1 Doc action, as most proteins with
      this conserved domain inactivate GTPases through addition of an adenylyl group
      (also referred to as AMPylation). We demonstrated that P1 Doc added a single
      phosphate group to the essential translation elongation factor and GTPase,
      elongation factor (EF)-Tu. The phosphorylation site was at a highly conserved
      threonine, Thr-382, which was blocked when EF-Tu was treated with the antibiotic
      kirromycin. Therefore, we have established that Fic domain proteins can function
      as kinases. This distinct enzymatic activity exhibited by P1 Doc also solves the
      mystery of the degenerate Fic motif unique to the Doc family of toxins. Moreover,
      we have established that all characterized Fic domain proteins, even those that
      phosphorylate, target pivotal GTPases for inactivation through a post
      translational modification at a single functionally critical acceptor site. 

PMID- 24448801
TI  - Calcium efflux activity of plasma membrane Ca2+ ATPase-4 (PMCA4) mediates cell
      cycle progression in vascular smooth muscle cells.
AB  - We explored the role played by plasma membrane calcium ATPase-4 (PMCA4) and its
      alternative splice variants in the cell cycle of vascular smooth muscle cells
      (VSMC). A novel variant (PMCA4e) was discovered. Quantitative real-time-PCR
      quantified PMCA4 splice variant proportions differed in specific organs. The
      PMCA4a:4b ratio in uninjured carotid arteries (~1:1) was significantly reduced by
      wire denudation injury (to ~1:3) by modulation of alternative splicing, as
      confirmed by novel antibodies against PMCA4a/e and PMCA4b. Laser capture
      microdissection localized this shift to the media and adventitia. Primary carotid
      VSMC from PMCA4 knock-out (P4KO) mice showed impaired [(3)H]thymidine
      incorporation and G1 phase arrest as compared with wild type (P4WT).
      Electroporation of expression constructs encoding PMCA4a, PMCA4b, and a PMCA4b
      mutant lacking PDZ binding rescued this phenotype of P4KO cells, whereas a mutant
      with only 10% of normal Ca(2+) efflux activity could not. Microarray of early G1
      synchronized VSMC showed 39-fold higher Rgs16 (NFAT (nuclear factor of activated
      T-cells) target; MAPK inhibitor) and 69-fold higher Decorin (G1 arrest marker)
      expression in P4KO versus P4WT. Validation by Western blot also revealed
      decreased levels of Cyclin D1 and NFATc3 in P4KO. Microarrays of P4KO VSMC
      rescued by PMCA4a or PMCA4b expression showed reversal of perturbed Rgs16,
      Decorin, and NFATc3 expression levels. However, PMCA4a rescue caused a 44-fold
      reduction in AP-2beta, a known anti-proliferative transcription factor, whereas
      PMCA4b rescue resulted in a 50-fold reduction in p15 (Cyclin D1/Cdk4 inhibitor).
      We conclude that Ca(2+) efflux activity of PMCA4 underlies G1 progression in VSMC
      and that PMCA4a and PMCA4b differentially regulate specific downstream mediators.

PMID- 24448802
TI  - Cigarette smoke-induced Ca2+ release leads to cystic fibrosis transmembrane
      conductance regulator (CFTR) dysfunction.
AB  - Chronic obstructive pulmonary disease affects 64 million people and is currently
      the fourth leading cause of death worldwide. Chronic obstructive pulmonary
      disease includes both emphysema and chronic bronchitis, and in the case of
      chronic bronchitis represents an inflammatory response of the airways that is
      associated with mucus hypersecretion and obstruction of small airways. Recently,
      it has emerged that exposure to cigarette smoke (CS) leads to an inhibition of
      the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel,
      causing airway surface liquid dehydration, which may play a role in the
      development of chronic bronchitis. CS rapidly clears CFTR from the plasma
      membrane and causes it to be deposited into aggresome-like compartments. However,
      little is known about the mechanism(s) responsible for the internalization of
      CFTR following CS exposure. Our studies revealed that CS triggered a rise in
      cytoplasmic Ca(2+) that may have emanated from lysosomes. Furthermore, chelation
      of cytoplasmic Ca(2+), but not inhibition of protein kinases/phosphatases,
      prevented CS-induced CFTR internalization. The macrolide antibiotic bafilomycin
      A1 inhibited CS-induced Ca(2+) release and prevented CFTR clearance from the
      plasma membrane, further linking cytoplasmic Ca(2+) and CFTR internalization. We
      hypothesize that CS-induced Ca(2+) release prevents normal sorting/degradation of
      CFTR and causes internalized CFTR to reroute to aggresomes. Our data provide
      mechanistic insight into the potentially deleterious effects of CS on airway
      epithelia and outline a hitherto unrecognized signaling event triggered by CS
      that may affect the long term transition of the lung into a hyper
      inflammatory/dehydrated environment. 

PMID- 24448803
TI  - Structural requirements for the antiviral activity of the human MxA protein
      against Thogoto and influenza A virus.
AB  - The interferon-induced dynamin-like MxA protein has broad antiviral activity
      against many viruses, including orthomyxoviruses such as influenza A and Thogoto
      virus and bunyaviruses such as La Crosse virus. MxA consists of an N-terminal
      globular GTPase domain, a connecting bundle signaling element, and the C-terminal
      stalk that mediates oligomerization and antiviral specificity. We previously
      reported that the disordered loop L4 that protrudes from the compact stalk is a
      key determinant of antiviral specificity against influenza A and Thogoto virus.
      However, the role of individual amino acids for viral target recognition remained
      largely undefined. By mutational analyses, we identified two regions in the C
      terminal part of L4 that contribute to an antiviral interface. Mutations in the
      proximal motif, at positions 561 and 562, abolished antiviral activity against
      orthomyxoviruses but not bunyaviruses. In contrast, mutations in the distal
      motif, around position 577, abolished antiviral activity against both viruses.
      These results indicate that at least two structural elements in L4 are
      responsible for antiviral activity and that the proximal motif determines
      specificity for orthomyxoviruses, whereas the distal sequence serves a conserved
      structural function. 

PMID- 24448804
TI  - SOD2 to SOD1 switch in breast cancer.
AB  - Cancer cells are characterized by elevated levels of reactive oxygen species,
      which are produced mainly by the mitochondria. The dismutase SOD2 localizes in
      the matrix and is a major antioxidant. The activity of SOD2 is regulated by the
      deacetylase SIRT3. Recent studies indicated that SIRT3 is decreased in 87% of
      breast cancers, implying that the activity of SOD2 is compromised. The resulting
      elevation in reactive oxygen species was shown to be essential for the metabolic
      reprograming toward glycolysis. Here, we show that SOD2 itself is down-regulated
      in breast cancer cell lines. Further, activation of oncogenes, such as Ras,
      promotes the rapid down-regulation of SOD2. Because in the absence of SOD2,
      superoxide levels are elevated in the matrix, we reasoned that mechanisms must
      exist to retain low levels of superoxide in other cellular compartments
      especially in the intermembrane space of the mitochondrial to avoid irreversible
      damage. The dismutase SOD1 also acts as an antioxidant, but it localizes to the
      cytoplasm and the intermembrane space of the mitochondria. We report here that
      loss of SOD2 correlates with the overexpression of SOD1. Further, we show that
      mitochondrial SOD1 is the main dismutase activity in breast cancer cells but not
      in non-transformed cells. In addition, we show that the SOD1 inhibitor LCS-1
      leads to a drastic fragmentation and swelling of the matrix, suggesting that in
      the absence of SOD2, SOD1 is required to maintain the integrity of the organelle.
      We propose that by analogy to the cadherin switch during epithelial-mesenchymal
      transition, cancer cells also undergo a SOD switch during transformation. 

PMID- 24448805
TI  - Enhanced enzyme kinetic stability by increasing rigidity within the active site.
AB  - Enzyme stability is an important issue for protein engineers. Understanding how
      rigidity in the active site affects protein kinetic stability will provide new
      insight into enzyme stabilization. In this study, we demonstrated enhanced
      kinetic stability of Candida antarctica lipase B (CalB) by mutating the
      structurally flexible residues within the active site. Six residues within 10 A
      of the catalytic Ser(105) residue with a high B factor were selected for
      iterative saturation mutagenesis. After screening 2200 colonies, we obtained the
      D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 
      degrees C and a 12  degrees C higher T50(15), the temperature at which enzyme
      activity is reduced to 50% after a 15-min heat treatment. Further
      characterization showed that global unfolding resistance against both thermal and
      chemical denaturation also improved. Analysis of the crystal structures of wild
      type CalB and the D223G/L278M mutant revealed that the latter formed an extra
      main chain hydrogen bond network with seven structurally coupled residues within
      the flexible alpha10 helix that are primarily involved in forming the active
      site. Further investigation of the relative B factor profile and molecular
      dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of
      the active site residues at high temperature. These results indicate that
      enhancing the rigidity of the flexible segment within the active site may provide
      an efficient method for improving enzyme kinetic stability. 

PMID- 24448806
TI  - Rubredoxin-related maturation factor guarantees metal cofactor integrity during
      aerobic biosynthesis of membrane-bound [NiFe] hydrogenase.
AB  - The membrane-bound [NiFe] hydrogenase (MBH) supports growth of Ralstonia eutropha
      H16 with H2 as the sole energy source. The enzyme undergoes a complex
      biosynthesis process that proceeds during cell growth even at ambient O2 levels
      and involves 14 specific maturation proteins. One of these is a rubredoxin-like
      protein, which is essential for biosynthesis of active MBH at high oxygen
      concentrations but dispensable under microaerobic growth conditions. To obtain
      insights into the function of HoxR, we investigated the MBH protein purified from
      the cytoplasmic membrane of hoxR mutant cells. Compared with wild-type MBH, the
      mutant enzyme displayed severely decreased hydrogenase activity. Electron
      paramagnetic resonance and infrared spectroscopic analyses revealed features
      resembling those of O2-sensitive [NiFe] hydrogenases and/or oxidatively damaged
      protein. The catalytic center resided partially in an inactive Niu-A-like state,
      and the electron transfer chain consisting of three different Fe-S clusters
      showed marked alterations compared with wild-type enzyme. Purification of HoxR
      protein from its original host, R. eutropha, revealed only low protein amounts.
      Therefore, recombinant HoxR protein was isolated from Escherichia coli. Unlike
      common rubredoxins, the HoxR protein was colorless, rather unstable, and
      essentially metal-free. Conversion of the atypical iron-binding motif into a
      canonical one through genetic engineering led to a stable reddish rubredoxin.
      Remarkably, the modified HoxR protein did not support MBH-dependent growth at
      high O2. Analysis of MBH-associated protein complexes points toward a specific
      interaction of HoxR with the Fe-S cluster-bearing small subunit. This supports
      the previously made notion that HoxR avoids oxidative damage of the metal centers
      of the MBH, in particular the unprecedented Cys6[4Fe-3S] cluster. 

PMID- 24448807
TI  - Transcriptional repression of the transforming growth factor beta (TGF-beta)
      Pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) by Nuclear Factor
      kappaB (NF-kappaB) p50 enhances TGF-beta signaling in hepatic stellate cells.
AB  - TLR4 signaling induces down-regulation of the bone morphogenic protein (BMP) and
      activin membrane-bound inhibitor (BAMBI), which enhances TGF-beta signaling
      during hepatic stellate cell (HSC) activation. We investigated the mechanism by
      which TLR4 signaling down-regulates BAMBI expression in HSCs and found that TLR4-
      and TNF-alpha-mediated BAMBI down-regulation is dependent on regulation of BAMBI
      promoter activity through the interaction with NF-kappaBp50 and HDAC1 in HSCs.
      Bambi was predominantly expressed in HSCs, at high levels in quiescent HSCs but
      at low levels in in vivo-activated and LPS-stimulated HSCs. In human HSCs, BAMBI
      expression was down-regulated in response to LPS and TNF-alpha. A BAMBI reporter
      assay demonstrated that the regulatory element to repress BAMBI transcription is
      located between 3384 and 1560 bp upstream from the transcription start site. LPS
      stimulation down-regulated BAMBI expression in cells with NF-kappaBp65 knockdown.
      However, it failed to down-regulate BAMBI in cells with inactivation of NF-kappaB
      or NF-kappaBp50 silencing, indicating that NF-kappaBp50 is a factor for BAMBI
      down-regulation. ChIP analysis revealed that LPS and TNF-alpha induced binding of
      the NF-kappaBp50/p50 homodimer to the BAMBI promoter region. We also found that
      HDAC1 is bound to this region as part of the NF-kappaBp50-HDAC1 complex,
      repressing transcriptional activity of the BAMBI promoter. Finally, we confirmed
      that LPS does not repress BAMBI reporter activity using a BAMBI reporter
      construct with a mutation at 3166 bp upstream of the coding region. In summary,
      our study demonstrates that LPS- and TNF-alpha-induced NF-kappaBp50-HDAC1
      interaction represses BAMBI transcriptional activity, which contributes to TLR4
      mediated enhancement of TGF-beta signaling in HSCs during liver fibrosis. 

PMID- 24448808
TI  - Phosphoinositide kinases play key roles in norepinephrine- and angiotensin II
      induced increase in phosphatidylinositol 4,5-bisphosphate and modulation of
      cardiac function.
AB  - The seemly paradoxical Gq agonist-stimulated phosphoinositide production has long
      been known, but the underlying mechanism and its physiological significance are
      not known. In this study, we studied cardiac phosphoinositide levels in both
      cells and whole animals under the stimulation of norepinephrine (NE), angiotensin
      II (Ang II), and other physiologically relevant interventions. The results
      demonstrated that activation of membrane receptors related to NE or Ang II caused
      an initial increase and a later fall in phosphatidylinositol 4,5-bisphosphate
      (PIP2) levels in the primary cultured cardiomyocytes from adult rats. The
      possible mechanism underlying this increase in PIP2 was found to be through an
      enhanced activity of phosphatidylinositol 4-kinase IIIbeta, which was mediated by
      an up-regulated interaction between phosphatidylinositol 4-kinase IIIbeta and
      PKC; the increased activity of phosphatidylinositol 4-phosphate 5-kinase gamma
      was also involved for NE-induced increase of PIP2. When the systolic functions of
      the NE/Ang II-treated cells were measured, a maintained or failed contractility
      was found to be correlated with a rise or fall in corresponding PIP2 levels. In
      two animal models of cardiac hypertrophy, PIP2 levels were significantly reduced
      in hypertrophic hearts induced by isoprenaline but not in those induced by
      swimming exercise. This study describes a novel mechanism for phosphoinositide
      metabolism and modulation of cardiac function. 

PMID- 24448809
TI  - [Retinal vascular diseases reflecting generalized vascular alterations. What can
      be mutually learnt?].
AB  - Retinal vascular diseases are mostly caused by systemic vascular diseases. In
      some cases the systemic disease is already known but in other patients ocular
      anomalies often provide the first indications of a systemic disease. Treating
      patients with vascular fundus diseases requires close cooperation between
      ophthalmologists and specialists in other fields and deciding which routine and
      specialized diagnostic examinations are necessary in light of the potential risk
      factors involved requires interdisciplinary communication. This article aims to
      provide an overview of the most important vascular retinal diseases and which
      examinations are required to ensure an accurate diagnosis. The retinal vascular
      diseases with the highest frequency or clinical relevance are hypertensive
      retinopathy, diabetic retinopathy, retinal vein occlusion and retinal artery
      occlusion. 

PMID- 24448810
TI  - [Interdisciplinary interaction for vascular diseases of the eye. Neurological
      differential diagnosis].
AB  - BACKGROUND: Vascular diseases of the eye are common and may be indicative of
      cerebrovascular diseases. OBJECTIVE: The aim was to describe the significance of
      neurological evaluation in patients with vascular diseases of the eye. METHODS: A
      selective literature research using PubMed was performed taking personal
      experiences as well as recommendations of international and national guidelines
      into consideration. RESULTS: Patients with transient blindness (amaurosis fugax)
      have a 4-fold higher risk of stroke during the year following onset of optical
      symptoms. These patients should be treated with platelet antiaggregants, such as
      100 mg/day acetylsalicylic acid (ASS). Patients with > 70 % stenosis of the
      ipsilateral internal carotid artery should be evaluated for carotid
      endarterectomy. Colloidal solutions should not be used in patients with
      cerebrovascular diseases. Avoiding nocturnal blood pressure drop may help to
      prevent anterior ischemic optical neuropathy in patients with carotid artery
      disease. Patients with ocular ischemic syndrome often have severe stenosis or
      occlusion of the internal carotid artery. Duplex ultrasound is the most important
      diagnostic test. CONCLUSION: Vascular diseases of the eye are frequently
      associated with cerebrovascular disease. A comprehensive vascular evaluation can
      contribute to prevention of stroke.

PMID- 24448811
TI  - [Interdisciplinary interaction in vascular diseases of the eye, diabetes and
      diabetic retinopathy].
AB  - The incidence of diabetes mellitus type 2 is greatly increasing worldwide. An
      early therapy with intensified control of diabetes and blood pressure is
      especially important to avoid delayed complications. In addition to diabetic foot
      syndrome, diabetic retinopathy and diabetic nephropathy still represent commonly
      occurring problems. Despite improvements in the quality of care, the targets of
      the St. Vincent Declaration have still not yet been achieved. Diabetic
      retinopathy and diabetic nephropathy show parallels in the course of the disease
      and in the pathological anatomical alterations which have led to the inauguration
      of a diabetic renal-retinal syndrome. The ophthalmological assessment of the
      retina was previously considered to be a diagnostic aid for assessment of
      diabetic nephropathy; however, nowadays a simple estimation of the glomerular
      filtration rate using the modification of diet in renal disease (MDRD) formula
      and determination of microalbuminuria can in contrast give ophthalmologists an
      early indication of the possible presence of microangiopathic alterations. 

PMID- 24448812
TI  - [Cardiovascular and hemostaseological view of retinal vascular occlusions].
AB  - BACKGROUND: Sudden pain-free impairment of vision often occurs due to acute
      occlusions of retinal blood vessels. Retinal vascular occlusion can be
      distinguished into the more frequent venous and to a lesser degree arterial
      events but mixed pictures also occur. OBJECTIVES: Summary of the current
      literature regarding interdisciplinary diagnosis and therapy of retinal blood
      vessel occlusions. MATERIALS AND METHODS: Selective literature review considering
      clinically relevant cardiovascular and hemostaseological aspects. RESULTS: The
      anatomical localization of the occlusion by the ophthalmologist can give
      important indications for further medical diagnostic and therapeutic decisions.
      Arterial occlusions are mostly caused by thromboembolisms and the source should
      be identified and treated. Venous occlusions are mostly due to local processes
      with a prothrombotic background or venous stasis associated with arterial
      hypertension. Prognostically, the localization, extent and duration of retinal
      ischemia are decisive factors. CONCLUSIONS: Vascular ocular occlusions are
      frequently secondary to internal disorders and therefore pose an
      interdisciplinary challenge.

PMID- 24448813
TI  - [Femtosecond lasers for cataract and refractive lens surgery].
AB  - The femtosecond laser technology continues its progress in ophthalmology and now
      also plays an increasingly important role in lens surgery. Using this technology
      it is possible to create corneal sections and to perform capsulorhexis and lens
      fragmentation. There are currently four instruments on the market with more to
      follow. The individual benefits and also critical issues are presented and the
      results of current studies are discussed. 

PMID- 24448814
TI  - [Atraumatic amniotic membrane transplantation].

PMID- 24448815
TI  - [Early recognition of keratoconus by biomechanical characteristics of the
      cornea].

PMID- 24448816
TI  - [Differential diagnosis and therapy of pigment epithelial detachment].
AB  - Retinal pigment epithelial detachment (PED) can occur associated with multiple
      ocular and infrequently also primarily non-ocular pathologies. They can be sub
      divided into drusenoid, serous, serous-vascularized and fibrovascular PED. Most
      commonly PED is found in age-related macular degeneration. The knowledge of
      possible differential diagnoses is important for the prognosis and helps in the
      choice of therapy and in the individual counseling of patients. 

PMID- 24448817
TI  - A suspected case of coronary periarteritis due to IgG4-related disease as a cause
      of ischemic heart disease.

PMID- 24448818
TI  - PP2A inhibition is a common event in colorectal cancer and its restoration using
      FTY720 shows promising therapeutic potential.
AB  - Protein phosphatase 2A (PP2A) is a tumor suppressor that regulates many signaling
      pathways crucial for cell transformation. In fact, decreased activity of PP2A has
      been reported as a recurrent alteration in many types of cancer. Here, we show
      that PP2A is frequently inactivated in patients with colorectal cancer,
      indicating that PP2A represents a potential therapeutic target for this disease.
      We identified overexpression of the endogenous PP2A inhibitors SET and CIP2A, and
      downregulation of regulatory PP2A such as PPP2R2A and PPP2R5E, as contributing
      mechanisms to PP2A inhibition in colorectal cancer. Moreover, we observed that
      its restoration using FTY720 impairs proliferation and clonogenic potential of
      colorectal cancer cells, induces caspase-dependent apoptosis, and affects AKT and
      extracellular signal-regulated kinase-1/2 activation status. Interestingly,
      treatment with FTY720 showed an additive effect with 5-fluorouracil, SN-38, and
      oxaliplatin, drugs used in standard chemotherapy in patients with colorectal
      cancer. These results suggest that PP2A activity is commonly decreased in
      colorectal cancer cells, and that the use of PP2A activators, such as FTY720,
      might represent a potential novel therapeutic strategy in colorectal cancer.

PMID- 24448819
TI  - Combinatorial therapy using dovitinib and ICI182.780 (fulvestrant) blocks tumoral
      activity of endometrial cancer cells.
AB  - Mutations in fibroblast growth factor receptor 2 (FGFR2) have been recently
      described as a molecular-specific feature in endometrial carcinomas and the
      presence of activated FGFR2 mutations is associated with poor prognosis. For that
      reason, inhibition of FGFR2 could be a therapeutic target in the treatment of
      endometriod carcinomas. In this work, we investigated the antitumoral activity of
      dovitinib (a multiple kinase inhibitor) in human endometrial cancer cell (ECC)
      lines. We found that dovitinib caused cell growth arrest, loss of clonogenic
      growth, and cell-cycle arrest in FGFR2-mutated ECCs in in vitro and in vivo
      experiments. Next, we investigated the mechanistic basis of dovitinib effects. We
      could determine that dovitinib modified expression levels of well-known key cell
      cycle regulatory proteins that induce cellular senescence. To further investigate
      the role of dovitinib, we analyzed its effect on estrogen receptor alpha (ER
      alpha) expression. Surprisingly, we discovered that dovitinib enhances ER-alpha
      expression in FGFR2-mutant ECCs. Because blocking one signaling pathway is often
      not sufficient to cause total tumor regression and the effectiveness of
      individual inhibitors is often short-lived, we examined the impact of targeting
      FGFR2 with dovitinib in combination with a selective ER antagonist, fulvestrant
      (ICI182.780). Combination of dovitinib plus ICI182.780 resulted in a
      significantly higher inhibition of cell growth than dovitinib treatment alone.
      These findings suggest that combinatory therapies using dovitinib plus ICI182.780
      treatment can be truly effective in patients with endometrial carcinomas carrying
      FGFR2 mutations.

PMID- 24448820
TI  - Decreased miR-340 expression in bone marrow is associated with liver metastasis
      of colorectal cancer.
AB  - Studies have shown the prognostic significance of disseminated tumor cells (DTC)
      in bone marrow of patients with colorectal cancer. However, the molecular
      characteristics of DTCs, including their miRNA expression profiles, remain mostly
      unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow.
      EpCAM(+) bone marrow cells were collected using immunomagnetic beads after
      exclusion of CD14(+) and CD45(+) cells, then subjected to miRNA microarray
      analysis. Cluster analysis (7 colorectal cancer patients with liver metastasis
      and 12 colorectal cancer patients without liver metastasis) indicated that miR
      340 and miR-542-3p expressions were significantly decreased in EpCAM(+) bone
      marrow cells of patients with liver metastasis (P = 0.019 and 0.037,
      respectively). We demonstrated that pre-miR-340 administration inhibited growth
      of colon cancer cells and suppressed c-Met expression in vitro. In clinical
      samples of colorectal cancer, miR-340 was expressed at significantly lower levels
      in tumor tissues compared with normal mucosa. Survival analysis in 136 patients
      with colorectal cancer indicated that low miR-340 expression was correlated with
      shorter 5-year disease-free survival (P = 0.023) and poor 5-year overall survival
      (P = 0.046). It was of note that the colorectal cancer group with low miR-340 and
      high c-Met expression had the worst prognosis. We further demonstrated that
      systemic pre-miR-340 administration suppressed growth of pre-established HCT116
      tumors in animal therapeutic models. These findings indicate that miR-340 may be
      useful as a novel prognostic factor and as a therapeutic tool against colorectal
      cancer. Our data suggest that miR-340 in bone marrow may play an important role
      in regulating the metastasis cascade of colorectal cancer.

PMID- 24448821
TI  - Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib
      resistant melanoma harboring the MEK1-C121S mutation in a preclinical model.
AB  - Many clinical cases of acquired resistance to the BRAF inhibitor vemurafenib have
      recently been reported. One of the causes of this acquired resistance is the BRAF
      downstream kinase point mutation MEK1-C121S. This mutation confers resistance to
      not only vemurafenib, but also to the allosteric MEK inhibitor selumetinib
      (AZD6244). Here, we investigated the pharmacologic activities and effectiveness
      of the novel MEK inhibitor E6201 against BRAF (v-raf murine sarcoma viral
      oncogene homolog B1)-V600E mutant melanoma harboring the MEK1-C121S mutation. A
      cell-free assay confirmed that E6201 is an ATP-competitive MEK inhibitor, meaning
      it has a different binding mode with MEK compared with allosteric MEK inhibitors.
      E6201 is more effective against BRAF-V600E mutant melanoma compared with BRAF
      wild-type melanoma based on MEK inhibition. We found that the acquired MEK1-C121S
      mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib
      and selumetinib but not E6201. The effectiveness of E6201 in this preclinical
      study is a result of its binding with MEK1 far from the C121S point mutation so
      the mutation is unable to influence the MAPK pathway inhibitory activity. These
      results support further clinical investigation of E6201.

PMID- 24448823
TI  - Evidence for mitochondrial localization of divalent metal transporter 1 (DMT1).
AB  - In mammalian cells, mitochondria receive most incoming iron, yet no entry pathway
      for iron at the outer mitochondrial membrane (OMM) has been characterized. Our
      results show that the divalent metal transporter 1 (DMT1) occurs in the OMM.
      Immunoblots detected DMT1 in mitochondria from a pneumocyte cell model in their
      OMM. Using the split-ubiquitin yeast 2-hybrid system, we found that cytochrome c
      oxidase subunit II (COXII) and the translocase of OMM 6-kDa subunit (Tom6)
      homologue interact with DMT1. COXII coimmunoprecipitates with DMT1. There are 4
      DMT1 isoforms that differ at the N and C termini. Using HEK293 cells that
      inducibly express all of the 4 ends of DMT1, we found all of them in the OMM, as
      detected by immunoblots after cell fractionation, and in isolated mitochondria,
      as detected by immunofluorescence. Immunoblot analysis of purified cell fractions
      from rat renal cortex confirmed and extended these results to the kidney, which
      expressed high levels of DMT1. Immunogold labeling detected DMT1 colocalization
      in mitochondria with the voltage-dependent anion-selective channel protein-1,
      which is expressed in the OMM. We suggest that DMT1 not only exports iron from
      endosomes, but also serves to import the metal into the mitochondria.

PMID- 24448822
TI  - Rationale and preclinical efficacy of a novel anti-EMP2 antibody for the
      treatment of invasive breast cancer.
AB  - Despite significant advances in biology and medicine, the incidence and mortality
      due to breast cancer worldwide is still unacceptably high. Thus, there is an
      urgent need to discover new molecular targets. In this article, we show evidence
      for a novel target in human breast cancer, the tetraspan protein epithelial
      membrane protein-2 (EMP2). Using tissue tumor arrays, protein expression of EMP2
      was measured and found to be minimal in normal mammary tissue, but it was
      upregulated in 63% of invasive breast cancer tumors and in 73% of triple-negative
      tumors tested. To test the hypothesis that EMP2 may be a suitable target for
      therapy, we constructed a fully human immunoglobulin G1 (IgG1) antibody specific
      for a conserved domain of human and murine EMP2. Treatment of breast cancer cells
      with the anti-EMP2 IgG1 significantly inhibited EMP2-mediated signaling, blocked
      FAK/Src signaling, inhibited invasion, and promoted apoptosis in vitro. In both
      human xenograft and syngeneic metastatic tumor monotherapy models, anti-EMP2 IgG1
      retarded tumor growth without detectable systemic toxicity. This antitumor effect
      was, in part, attributable to a potent antibody-dependent cell-mediated
      cytotoxicity response as well as direct cytotoxicity induced by the monoclonal
      antibody. Together, these results identify EMP2 as a novel therapeutic target for
      invasive breast cancer.

PMID- 24448824
TI  - Adjunctive beta2-agonist treatment reduces glycogen independently of receptor
      mediated acid alpha-glucosidase uptake in the limb muscles of mice with Pompe
      disease.
AB  - Enzyme or gene replacement therapy with acid alpha-glucosidase (GAA) has achieved
      only partial efficacy in Pompe disease. We evaluated the effect of adjunctive
      clenbuterol treatment on cation-independent mannose-6-phosphate receptor (CI-MPR)
      mediated uptake and intracellular trafficking of GAA during muscle-specific GAA
      expression with an adeno-associated virus (AAV) vector in GAA-knockout (KO) mice.
      Clenbuterol, which increases expression of CI-MPR in muscle, was administered
      with the AAV vector. This combination therapy increased latency during rotarod
      and wirehang testing at 12 wk, in comparison with vector alone. The mean urinary
      glucose tetrasaccharide (Glc4), a urinary biomarker, was lower in GAA-KO mice
      following combination therapy, compared with vector alone. Similarly, glycogen
      content was lower in cardiac and skeletal muscle following 12 wk of combination
      therapy in heart, quadriceps, diaphragm, and soleus, compared with vector alone.
      These data suggested that clenbuterol treatment enhanced trafficking of GAA to
      lysosomes, given that GAA was expressed within myofibers. The integral role of CI
      MPR was demonstrated by the lack of effectiveness from clenbuterol in GAA-KO mice
      that lacked CI-MPR in muscle, where it failed to reverse the high glycogen
      content of the heart and diaphragm or impaired wirehang performance. However, the
      glycogen content of skeletal muscle was reduced by the addition of clenbuterol in
      the absence of CI-MPR, as was lysosomal vacuolation, which correlated with
      increased AKT signaling. In summary, beta2-agonist treatment enhanced CI-MPR
      mediated uptake and trafficking of GAA in mice with Pompe disease, and a
      similarly enhanced benefit might be expected in other lysosomal storage
      disorders.

PMID- 24448825
TI  - Characterization and evaluation of (64)Cu-labeled A20FMDV2 conjugates for imaging
      the integrin alphavbeta 6.
AB  - PURPOSE: The integrin alphavbeta6 is overexpressed in a variety of aggressive
      cancers and serves as a prognosis marker. This study describes the conjugation,
      radiolabeling, and in vitro and in vivo evaluation of four chelators to determine
      the best candidate for (64)Cu radiolabeling of A20FMDV2, an alphavbeta6 targeting
      peptide. PROCEDURES: Four chelators were conjugated onto PEG28-A20FMDV2 (1): 11
      carboxymethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4-methanephosphonic acid
      (CB-TE1A1P), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA),
      1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and 4,4'-((3,6,10,13,16,19
      hexazazbicyclo[6.6.6]ico-sane-1,8-diylbis(aza-nediyl))bis(methylene)dibenzoic
      acid (BaBaSar). All peptides were radiolabeled with (64)Cu in ammonium acetate
      buffer at pH 6 and formulated to pH 7.2 in PBS for use. The radiotracers were
      evaluated using in vitro cell binding and internalization assays and serum
      stability assays. In vivo studies conducted include blocking, biodistribution,
      and small animal PET imaging. Autoradiography and histology were also conducted.
      RESULTS: All radiotracers were radiolabeled in good radiochemical purity (>95 %)
      under mild conditions (37-50  degrees C for 15 min) with high specific activity
      (0.58-0.60 Ci/MUmol). All radiotracers demonstrated alphavbeta6-directed cell
      binding (>46 %) with similar internalization levels (>23 %). The radiotracers
      (64)Cu-CB-TE1A1P-1 and (64)Cu-BaBaSar-1 showed improved specificity for the
      alphavbeta6 positive tumor in vivo over (64)Cu-DOTA-1 and (64)Cu-NOTA-1 (+/-
      tumor uptake ratios-3.82 +/- 0.44, 3.82 +/- 0.41, 2.58 +/- 0.58, and 1.29 +/-
      0.14, respectively). Of the four radiotracers, (64)Cu-NOTA-1 exhibited the
      highest liver uptake (10.83 +/- 0.1 % ID/g at 4 h). CONCLUSIONS: We have
      successfully conjugated, radiolabeled, and assessed the four chelates CB-TE1A1P,
      DOTA, NOTA, and BaBaSar both in vitro and in vivo. However, the data suggests no
      clear "best candidate" for the (64)Cu-radiolabeling of A20FMDV2, but instead a
      trade-off between the different properties (e.g., stability, selectivity,
      pharmacokinetics, etc.) with no obvious effects of the individual chelators.

PMID- 24448826
TI  - On the elastic properties of mineralized turkey leg tendon tissue: multiscale
      model and experiment.
AB  - The key parameters influencing the elastic properties of the mineralized turkey
      leg tendon (MTLT) were investigated. Two structurally different tissue types
      appearing in the MTLT were considered: circumferential and interstitial tissue.
      These differ in their amount of micropores and their average diameter of the
      mineralized collagen fibril bundles. A multiscale model representing the apparent
      elastic stiffness tensor of MTLT tissue was developed using the Mori-Tanaka and
      the self-consistent homogenization schemes. The volume fraction of mineral
      (hydroxyapatite) in the fibril bundle, [Formula: see text], and the tissue
      microporosity are the variables of the model. The MTLT model was analyzed
      performing a global sensitivity analysis (Elementary Effects method) and a
      parametric study. The stiffnesses parallel (axial) and perpendicular (transverse)
      to the MTLT long axis were the only significantly sensitive components of the
      apparent stiffness tensor of MTLT tissue. The most important parameters
      influencing these apparent stiffnesses are [Formula: see text], tissue
      microporosity, as well as shape and distribution of the minerals in the fibril
      bundle (intra- vs. interfibrillar). The predicted apparent stiffness was
      converted to acoustic impedance for model validation. From measurements on
      embedded MTLT samples, including 50- and 200-MHz scanning acoustic microscopy as
      well as synchrotron radiation micro-computed tomography, we obtained site-matched
      acoustic impedance and [Formula: see text] data of circumferential and
      interstitial tissue. The experimental and the model data compare very well for
      both tissue types (relative error 6-8 %). 

PMID- 24448827
TI  - Involvement of ERK and p38 MAPK pathways on Interleukin-33-induced RANKL
      expression in osteoblastic cells.
AB  - The receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) system
      is a well-known key factor in osteoclast differentiation, and osteoblastic
      lineage cells are the major sources of RANKL and OPG in local bone tissue.
      Recently, a new molecule from the interleukin (IL)-1 family, IL-33, was
      identified. Here, we report the possible involvement of IL-33 in RANKL and OPG
      expression, and the signaling pathways that are required for maximal IL-33
      induced RANKL expression in MC3T3-E1 osteoblastic cells. Stimulation with IL-33
      increased the mRNA expression and secretion of RANKL in MC3T3-E1 cells. The IL-33
      induced RANKL mRNA expression was inhibited by an anti-IL-33 monoclonal antibody.
      Furthermore, ERK and p38 MAPK inhibitors, but not a JNK inhibitor, suppressed IL
      33-induced RANKL mRNA expression. On the other hand, IL-33 had no effect on OPG
      mRNA expression and protein secretion. These results taken together suggest that
      IL-33 stimulates RANKL expression through mechanisms dependent on the ERK and p38
      MAPK pathways in MC3T3-E1 cells. 

PMID- 24448828
TI  - A concise formation of N-substituted 3,4-diarylpyrroles--synthesis and cytotoxic
      activity.
AB  - A short synthesis of N-substituted 3,4-diarylpyrroles by condensation of a
      phenacyl halide with a primary amine and a phenylacetaldehyde is reported. The
      key step is an intramolecular cyclization of an in situ generated enamine onto a
      ketone. Using differently substituted aromatic reactants and N-(3
      aminopropyl)azatricyclodecane as the amine component, the preparation of analogs
      of the cytotoxic marine alkaloid halitulin could be achieved. The cytotoxicity of
      some of the compounds obtained by this method was studied, and one of them proved
      to be a very potent derivative, acting at a nanomolar concentration, in a caspase
      independent cell death mechanism. 

PMID- 24448829
TI  - Microstructure characterization of a decellularized vocal fold scaffold for
      laryngeal tissue engineering.
AB  - OBJECTIVES/HYPOTHESIS: One potential treatment for vocal fold injury or neoplasia
      is to replace the entire vocal fold with a tissue-engineered scaffold. This
      scaffold should ideally have similar mechanical properties and extracellular
      matrix composition as the native vocal fold. As one approach toward this goal, we
      decellularized human vocal folds and characterized their mechanical properties
      and extracellular matrix microstructure. STUDY DESIGN: Basic science
      investigation. METHODS: Human vocal folds were dissected from the laryngeal
      framework and treated with sodium dodecyl sulfate (SDS) to remove all cells.
      Mechanical properties were measured by indentation before and after SDS
      treatment. The extracellular matrix components of collagen, laminin, elastin, and
      hyaluronic acid were also characterized before and after decellularization using
      histology and immunofluorescence. RESULTS: After 4 days of SDS treatment, we
      obtained a scaffold that retained the original geometry of the vocal fold but was
      devoid of cells. The elastic modulus of the vocal folds did not change
      significantly before and after decellularization. Upon qualitative inspection,
      the decellularized vocal folds retained the original collagen, elastin, and
      laminin content and orientation but lost the original hyaluronic acid.
      CONCLUSIONS: Vocal folds can be decellularized using SDS without adversely
      affecting its mechanical stiffness and fibrous extracellular matrix. This
      preliminary study demonstrates the potential of a decellularized scaffold to
      serve as a tissue-engineered construct for vocal fold replacement.

PMID- 24448830
TI  - Assessment of fetal midbrain and hindbrain in mid-sagittal cranial plane by three
      dimensional multiplanar sonography. Part 1: comparison of new and established
      nomograms.
AB  - OBJECTIVE: To construct nomograms for fetal midbrain (MB) and hindbrain (HB)
      dimensions, assessed in the mid-sagittal cranial plane by three-dimensional
      multiplanar sonographic reconstruction (3D-MPR). METHODS: This was a prospective
      cross-sectional study of 334 healthy fetuses in low-risk singleton pregnancies
      between 16 and 35 gestational weeks. All sonographic volumes were obtained by
      sagittal acquisition. The following MB and HB parameters were evaluated in the
      mid-sagittal cranial plane using 3D-MPR: MB parameters tectal length (TL) and
      anteroposterior midbrain diameter (APMD), and HB parameters anteroposterior pons
      diameter (APPD), superoinferior vermian diameter (SIVD), anteroposterior vermian
      diameter (APVD) and anteroposterior diameter of the fourth ventricle (APDFV). The
      measurements were presented as growth charts according to gestational age.
      RESULTS: MB and HB biometry were best assessed between 19 and 29 weeks. During
      this period, adequate visualization was achieved for successful measurement of TL
      in 90.9% of cases, APMD in 86.6%, APPD in 73.7%, SIVD in 74.2%, APVD in 71% and
      APDFV in 71%. There was a linear growth pattern, with Pearson correlation
      coefficients of 0.79 for TL, 0.88 for APMD, 0.91 for APPD, 0.95 for SIVD, 0.88
      for APVD and 0.88 for APDFV (P < 0.0001 for each). The mean intra- and
      interobserver variations for the MB measurements and vermian diameters ranged
      between 4.3% and 9%. APPD and APDFV showed highest mean variations: 9.0% and
      19.4% (intraobserver) and 11.6% and 17.7% (interobserver), respectively.
      CONCLUSION: We present new nomograms for assessment of the fetal MB and HB using
      3D-MPR in the mid-sagittal cranial plane. To our knowledge, these are the first
      proposed nomograms for fetal MB dimensions.

PMID- 24448831
TI  - Assessment of the reproductive toxicity of inhalation exposure to ethyl tertiary
      butyl ether in male mice with normal, low active and inactive ALDH2.
AB  - No data are available regarding aldehyde dehydrogenase 2 (ALDH2) polymorphisms
      related to the reproductive toxicity possibly caused by ethyl tertiary butyl
      ether (ETBE). In this study, two inhalation experiments were performed in Aldh2
      knockout (KO), heterogeneous (HT) and wild type (WT) C57BL/6 male mice exposed to
      ETBE, and the data about general toxicity, testicular histopathology, sperm head
      numbers, sperm motility and sperm DNA damage were collected. The results showed
      that the 13-week exposure to 0, 500, 1,750 and 5,000 ppm ETBE significantly
      decreased sperm motility and increased levels of sperm DNA strand breaks and 8
      hydroxy-deoxyguanosine in both WT and KO mice, the effects were found in 1,750
      and 5,000 ppm groups of WT mice, and all of the three exposed groups of KO mice
      compared to the corresponding control; furthermore, ETBE also caused decrease in
      the relative weights of testes and epididymides, the slight atrophy of
      seminiferous tubules of testis and reduction in sperm numbers of KO mice exposed
      to >=500 ppm. In the experiment of exposure to lower concentrations of ETBE (0,
      50, 200 and 500 ppm) for 9 weeks, the remarkable effects of ETBE on sperm head
      numbers, sperm motility and sperm DNA damage were further observed in KO and HT
      mice exposed to 200 ppm ETBE, but not in WT mice. Our findings suggested that
      only exposure to high concentrations of ETBE might result in reproductive
      toxicity in mice with normal active ALDH2, while low active and inactive ALDH2
      enzyme significantly enhanced the ETBE-induced reproductive toxicity in mice,
      even exposed to low concentrations of ETBE, mainly due to the accumulation of
      acetaldehyde as a primary metabolite of ETBE. 

PMID- 24448832
TI  - Nickel-induced cell death and survival pathways in cultured renal proximal tubule
      cells: roles of reactive oxygen species, ceramide and ABCB1.
AB  - Nickel and nickel compounds are carcinogens that target the lungs and kidneys
      causing cell death or cell survival adaptation. The multidrug resistance P
      glycoprotein ABCB1 protects cells against toxic metabolites and xenobiotics and
      is upregulated in many cancer cell types. Here, we investigated the role of ABCB1
      in nickel-induced stress signaling mediated by reactive oxygen species (ROS) and
      ceramides. In renal proximal tubule cells, nickel chloride (0.1-0.25 mM)
      increased both ROS formation, detected by 5-(and-6)-carboxy-2',7'
      dichlorodihydrofluorescein diacetate, and cellular ceramides, which were
      determined by lipid dot blot and surface immunostaining, culminating in decreased
      cell viability, increased DNA fragmentation, augmented PARP-1 cleavage, and
      increased ABCB1 mRNA and protein. Inhibitors of the de novo ceramide synthesis
      pathway (fumonisin B1, L-cycloserine) and an antioxidant (alpha-tocopherol)
      attenuated nickel-induced toxicity as well as induction of ABCB1. ABCB1 protects
      against nickel toxicity as PSC833, an ABCB1 blocker, augmented the decrease in
      cell viability by nickel. Moreover, nickel toxicity was attenuated in renal MDCK
      cells stably overexpressing ABCB1. In agreement with previous data that
      demonstrated extrusion of (glucosyl)ceramides by ABCB1 (Lee et al. in Toxicol Sci
      121:343, 2011), PSC833 increased total cellular ceramides by >2-fold after nickel
      treatment. Further, glucosylceramide synthase (GCS) mRNA is upregulated by nickel
      at 3 h by ~1.5-fold but declined with prolonged exposures (6-24 h). Inhibition of
      GCS with C9DGJ or knockdown of GCS with siRNA significantly attenuated nickel
      toxicity. In conclusion, nickel induces a ROS-ceramide pathway to cause apoptotic
      cell death as well as activate adaptive survival responses, including
      upregulation of ABCB1, which improves cell survival by extruding proapoptotic
      (glucosyl)ceramides. 

PMID- 24448833
TI  - Xanthine crystals induced by topiroxostat, a xanthine oxidoreductase inhibitor,
      in rats, cause transitional cell tumors.
AB  - The present study was performed to elucidate the underlying mechanism of
      transitional cell tumors found in the carcinogenicity testing of topiroxostat, a
      xanthine oxidoreductase inhibitor, in which topiroxostat was orally given to F344
      rats at 0.3, 1, and 3 mg/kg for 2 years. In the urinary bladder, transitional
      cell papillomas and/or carcinomas were seen in males receiving 0.3, 1, and 3
      mg/kg (1/49, 3/49, and 10/50, respectively). In the kidney, transitional cell
      papillomas and/or carcinomas in the pelvis were seen in 2/50 males and 1/50
      females receiving 3 mg/kg. In the mechanistic study by 52-week oral treatment
      with topiroxostat at 3 mg/kg to F344 male rats, with and without citrate, simple
      and papillary transitional cell hyperplasias of the urinary bladder epithelium
      were observed in 5/17 in the topiroxostat-alone treatment group, along with
      xanthine-induced nephropathy, in contrast to neither xanthine crystals nor
      lesions in urinary organs by co-treatment group with citrate. As for sex
      differences of urinary bladder tumors, the BrdU labeling index for epithelial
      cells of the urinary bladder by 5-week oral treatment with topiroxostat at 10
      mg/kg to F344 rats was increased in males only, showing consistency with
      histopathological findings. Therefore, the present study indicates that
      transitional cell tumors induced by topiroxostat in rats were due to physical
      stimulation to transitional cells of xanthine crystals/calculi and provides that
      other factors were not implicated in this tumorigenesis. Furthermore, the present
      study suggests that such tumors do not predict for humans since topiroxostat
      induced xanthine deposition is a rodent-specific event. 

PMID- 24448834
TI  - Genetic variations in TP53 binding sites are predictors of clinical outcomes in
      prostate cancer patients.
AB  - Since the tumor protein p53 (TP53), a transcription factor, plays a crucial role
      in prostate cancer development and progression, we hypothesized that sequence
      variants in TP53 binding sites might affect clinical outcomes in patients with
      prostate cancer. We systematically evaluated 41 single nucleotide polymorphisms
      (SNPs) within genome-wide predicted TP53 binding sites in a cohort of 1,024
      prostate cancer patients. The associations of these SNPs with prostate cancer
      characteristics and clinical outcomes after radical prostatectomy for localized
      disease and after androgen-deprivation therapy (ADT) for advanced disease were
      assessed by Kaplan-Meier analysis and Cox regression model. ARAP2 rs1444377 and
      TRPS1 rs722740 were associated with advanced stage prostate cancer. FRK rs171866
      remained as a significant predictor for disease progression; DAB2 rs268091 and
      EXOC4 rs1149558 remained as significant predictors for prostate cancer-specific
      mortality (PCSM); and EXOC4 rs1149558 remained as a significant predictor for all
      cause mortality after ADT in multivariate models that included clinicopathologic
      predictors. In addition, the numbers of protective genotypes at DAB2 rs268091 and
      EXOC4 rs1149558 showed a cumulative effect on PCSM (P for trend = 0.002). Our
      results suggested that SNPs within TP53 binding sites might be valuable
      biomarkers for prostate cancer outcome prediction. 

PMID- 24448835
TI  - Human stem cell-derived hepatocytes: breakthrough of an expedient tool for
      preclinical assessment of drug-induced liver injury?

PMID- 24448838
TI  - Quo vadis? Peering into the future.

PMID- 24448836
TI  - Predicting Alzheimer disease with beta-amyloid imaging: results from the
      Australian imaging, biomarkers, and lifestyle study of ageing.
AB  - OBJECTIVE: Biomarkers for Alzheimer disease (AD) can detect the disease pathology
      in asymptomatic subjects and individuals with mild cognitive impairment (MCI),
      but their cognitive prognosis remains uncertain. We aimed to determine the
      prognostic value of beta-amyloid imaging, alone and in combination with memory
      performance, hippocampal atrophy, and apolipoprotein E epsilon4 status in
      nondemented, older individuals. METHODS: A total of 183 healthy individuals (age
      = 72.0 +/- 7.26 years) and 87 participants with MCI (age = 73.7 +/- 8.27) in the
      Australian Imaging, Biomarkers, and Lifestyle study of ageing were studied.
      Clinical reclassification was performed after 3 years, blind to biomarker
      findings. beta-Amyloid imaging was considered positive if the (11) C-Pittsburgh
      compound B cortical to reference ratio was >=1.5. RESULTS: Thirteen percent of
      healthy persons progressed (15 to MCI, 8 to dementia), and 59% of the MCI cohort
      progressed to probable AD. Multivariate analysis showed beta-amyloid imaging as
      the single variable most strongly associated with progression. Of combinations,
      subtle memory impairment (Z score = -0.5 to -1.5) with a positive amyloid scan
      was most strongly associated with progression in healthy individuals (odds ratio
      [OR] = 16, 95% confidence interval [CI] = 3.7-68; positive predictive value [PPV]
      = 50%, 95% CI = 19-81; negative predictive value [NPV] = 94%, 95% CI = 88-98).
      Almost all amnestic MCI subjects (Z score <= -1.5) with a positive amyloid scan
      developed AD (OR = infinity; PPV = 86%, 95% CI = 72-95; NPV = 100%, 95% CI = 80
      100). Hippocampal atrophy and epsilon4 status did not add further predictive
      value. INTERPRETATION: Subtle memory impairment with a positive beta-amyloid scan
      identifies healthy individuals at high risk for MCI or AD. Clearly amnestic
      patients with a positive amyloid scan have prodromal AD and a poor prognosis for
      dementia within 3 years.

PMID- 24448839
TI  - Neuroscientists navigate divide on nonhuman primate research: new regulations
      concern some researchers, but others question the necessity of most research on
      nonhuman primates.

PMID- 24448840
TI  - Neurologist with vision: Shirley Wray brings a unique viewpoint to the
      understanding of neuro-ophthalmology-and the field of neurology.

PMID- 24448841
TI  - Diabetes and immunity to tuberculosis.
AB  - The dual burden of tuberculosis (TB) and diabetes has attracted much attention in
      the past decade as diabetes prevalence has increased dramatically in countries
      already afflicted with a high burden of TB. The confluence of these two major
      diseases presents a serious threat to global public health; at the same time it
      also presents an opportunity to learn more about the key elements of human
      immunity to TB that may be relevant to the general population. Some effects of
      diabetes on innate and adaptive immunity that are potentially relevant to TB
      defense have been identified, but have yet to be verified in humans and are
      unlikely to fully explain the interaction of these two disease states. This
      review provides an update on the clinical and epidemiological features of TB in
      the diabetic population and relates them to recent advances in understanding the
      mechanistic basis of TB susceptibility and other complications of diabetes.
      Issues that merit further investigation - such as geographic host and pathogen
      differences in the diabetes/TB interaction, the role of hyperglycemia-induced
      epigenetic reprogramming in immune dysfunction, and the impact of diabetes on
      lung injury and fibrosis caused by TB - are highlighted in this review. 

PMID- 24448842
TI  - Formyl peptide receptor suppresses melanoma development and promotes NK cell
      migration.
AB  - In order to understand how tumor cells can escape immune surveillance mechanisms
      and thus develop antitumor therapies, it is critically important to investigate
      the mechanisms by which the immune system interacts with the tumor
      microenvironment. In our current study, wild-type mice were inoculated with
      melanoma cell line B16-F10 (1 * 10(6)/mouse) and treated with the formyl peptide
      receptor (FPR) agonist WKYMVm or the FPR antagonist WRW(4). Growth of melanoma
      cell line B16-F10 was significantly inhibited in WKYMVm-treated mice and markedly
      promoted in WRW(4)-treated mice compared with control. Decreased number of
      myeloid-derived suppressor cells (MDSCs) and increased NK cell infiltration in
      tumor tissues were detected from WKYMVm-treated mice. Next, we showed that
      depletion of NK cell significantly increased tumor development in B16 tumor
      bearing mice compared with the control group, and the suppressed tumor-developing
      effect of WKYMVm in B16 melanoma was abrogated with NK cell depletion. We also
      found that WKYMVm stimulates chemotactic migration in NK cells via the FPR
      family, and this was dependent on extracellular signal-related kinase (ERK)
      activation. Moreover, in our further experiment, we showed that the increased
      infiltration of NK cell and promoted NK cell chemotaxis in B16 melanoma induced
      by WKYMVm were both abolished with ERK inhibitor PD98059 administration. In
      conclusion, the FPR family promoted NK cell migration through ERK activation and
      inhibited B16 melanoma growth in a murine model. 

PMID- 24448844
TI  - Bowel dysfunction after rectal cancer treatment: a study comparing the
      specialist's versus patient's perspective.
AB  - OBJECTIVES: To investigate how bowel dysfunction after sphincter-preserving
      rectal cancer treatment, known as low anterior resection syndrome (LARS), is
      perceived by rectal cancer specialists, in relation to the patient's experience.
      DESIGN: Questionnaire study. SETTING: International. PARTICIPANTS: 58 rectal
      cancer specialists (45 colorectal surgeons and 13 radiation oncologists).
      RESEARCH PROCEDURE: The Low Anterior Resection Syndrome Score (LARS score) is a
      five-item instrument for evaluation of LARS, which was developed from and
      validated on 961 patients. The 58 specialists individually completed two LARS
      score-based exercises. In Exercise 1, they were asked to select, from a list of
      bowel dysfunction issues, five items that they considered to disturb patients the
      most. In Exercise 2, they were given a list of scores to assign to the LARS score
      items, according to the impact on quality of life (QOL). OUTCOME MEASURES: In
      Exercise 1, the frequency of selection of each issue, particularly the five items
      included in the LARS score, was compared with the frequency of being selected at
      random. In Exercise 2, the answers were compared with the original patient
      derived scores. RESULTS: Four of the five LARS score issues had the highest
      frequencies of selection (urgency, clustering, incontinence for liquid stool and
      frequency of bowel movements), which were also higher than random. However, the
      remaining LARS score issue (incontinence for flatus) showed a lower frequency
      than random. Scores assigned by the specialists were significantly different from
      the patient-derived scores (p<0.01). The specialists grossly overestimated the
      impact of incontinence for liquid stool and frequent bowel movements on QOL,
      while they markedly underestimated the impact of clustering and urgency. The
      results did not differ between surgeons and oncologists. CONCLUSIONS: Rectal
      cancer specialists do not have a thorough understanding of which bowel
      dysfunction symptoms truly matter to the patient, nor how these symptoms affect
      QOL.

PMID- 24448843
TI  - Antihepatotoxic effect of tadehaginoside, extracted from Tadehagi triquetrum
      (L.), against CCl4-lesioned rats through activating the Nrf2 signaling pathway
      and attenuating the inflammatory response.
AB  - Recently, an increasing number of studies suggest that oxidative stress and
      inflammation are associated with hepatocellular injuries. Thus, we aimed to
      evaluate the potential hepatoprotective role of tadehaginoside (TA) on liver
      lesions induced by carbon tetrachloride (CCl4). The results in vitro suggested
      that TA dose-dependently suppressed the cell proliferation of HepG2 cells,
      whereas the phosphorylated level of IkappaBalpha in cells was effectively
      inactivated. The study in vivo showed that TA significantly lowered the serum
      concentrations of alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), immunoglobulin E (IgE), and leukotriene (LT) in CCl4-lesioned rats.
      Pathological examination indicated that CCl4-induced hepatocellular damage was
      effectively mitigated by TA treatment. Meanwhile, the contents of gamma
      glutamylcysteine synthetase (gamma-GCS), glutathione (GSH), and catalase (CAT) in
      liver tissue were gradually elevated. In addition, cytochrome c oxidase (COX)
      mRNA expression in hepatocytes was markedly upregulated, and nuclear factor E2
      related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keapl) levels
      were progressively increased. Furthermore, the tumor necrosis factor alpha (TNF
      alpha) and nuclear factor-kappa B (NF-kappaB)-expressed protein were
      downregulated. These findings demonstrate that tadehaginoside effectively
      protects against CCl4-induced oxidative injury and inflammatory reaction in
      hepatocytes, in which the underlying mechanisms are involved in activating the
      Nrf2 signaling pathway and inhibiting the NF-kappaB pathway, thereby attenuating
      oxidative stress and reducing the inflammation in liver cells. 

PMID- 24448845
TI  - Real-ear acoustical characteristics of impulse sound generated by golf drivers
      and the estimated risk to hearing: a cross-sectional study.
AB  - OBJECTIVES: This study investigated real-ear acoustical characteristics in terms
      of the sound pressure levels (SPLs) and frequency responses in situ generated
      from golf club drivers at impact with a golf ball. The risk of hearing loss
      caused by hitting a basket of golf balls using various drivers was then
      estimated. DESIGN: Cross-sectional study. SETTING: The three driver clubs were
      chosen on the basis of reflection of the commonality and modern technology of the
      clubs. The participants were asked to choose the clubs in a random order and hit
      six two-piece range golf balls with each club. The experiment was carried out at
      a golf driving range in South Wales, UK. PARTICIPANTS: 19 male amateur golfers
      volunteered to take part in the study, with an age range of 19-54 years. OUTCOME
      MEASURES: The frequency responses and peak SPLs in situ of the transient sound
      generated from the club at impact were recorded bilaterally and simultaneously
      using the GN Otometric Freefit wireless real-ear measurement system. A swing
      speed radar system was also used to investigate the relationship between noise
      level and swing speed. RESULTS: Different clubs generated significantly different
      real-ear acoustical characteristics in terms of SPL and frequency responses.
      However, they did not differ significantly between the ears. No significant
      correlation was found between the swing speed and noise intensity. On the basis
      of the SPLs measured in the present study, the percentage of daily noise exposure
      for hitting a basket of golf balls using the drivers described above was less
      than 2%. CONCLUSIONS: The immediate danger of noise-induced hearing loss for
      amateur golfers is quite unlikely. However, it may be dangerous to hearing if the
      noise level generated by the golf clubs exceeded 116 dBA.

PMID- 24448846
TI  - White matter integrity and cognition in Parkinson's disease: a cross-sectional
      study.
AB  - OBJECTIVE: We used diffusion tensor imaging (DTI) to test the following
      hypotheses: (1) there is decreased white matter (WM) integrity in non-demented
      Parkinson's disease (PD), (2) WM integrity is differentially reduced in PD and
      early Alzheimer's disease (AD) and (3) DTI changes in non-demented PD are
      specifically associated with cognitive performance. METHODS: This study included
      18 non-demented patients with PD, 18 patients with mild cognitive impairment due
      to incipient AD and 19 healthy elderly normal control (NC) participants in a
      cross-sectional design. The participants underwent DTI, and tract-based spatial
      statistics was used to analyse and extract radial diffusivity and fractional
      anisotropy. Correlations between scores from a battery of neuropsychological
      tests and DTI were performed in the PD group. RESULTS: Patients with PD had
      significant differences in DTI in WM underlying the temporal, parietal and
      occipital cortex as compared with NC. There were no significant differences
      between the PD and AD groups in the primary region of interest analyses, but
      compared with NC there was a tendency for more anterior changes in AD in contrast
      to more posterior changes in PD. In a secondary whole-brain analysis there were
      frontoparietal areas with significant differences between AD and PD. In patients
      with PD, there were significant correlations between DTI parameters in WM
      underlying the prefrontal cortex and executive and visuospatial abilities.
      CONCLUSIONS: In early, non-demented PD we found reduced WM integrity underlying
      the temporal, parietal and occipital cortices. In addition, WM integrity changes
      in prefrontal areas were associated with executive and visuospatial ability.
      These findings support that DTI may be an important biomarker in early PD, and
      that WM changes are related to cognitive impairment in PD.

PMID- 24448847
TI  - Diffusion of an evidence-based smoking cessation intervention through Facebook: a
      randomised controlled trial study protocol.
AB  - INTRODUCTION: Online social networks represent a potential mechanism for the
      dissemination of health interventions including smoking cessation; however, which
      elements of an intervention determine diffusion between participants is unclear.
      Diffusion is frequently measured using R, the reproductive rate, which is
      determined by the duration of use (t), the 'contagiousness' of an intervention
      (beta) and a participant's total contacts (z). We have developed a Facebook 'app'
      that allows us to enable or disable various components designed to impact the
      duration of use (expanded content, proactive contact), contagiousness (active and
      passive sharing) and number of contacts (use by non-smoker supporters). We
      hypothesised that these elements would be synergistic in their impact on R, while
      including non-smokers would induce a 'carrier' state allowing the app to bridge
      clusters of smokers. METHODS AND ANALYSIS: This study is a fractional factorial,
      randomised control trial of the diffusion of a Facebook application for smoking
      cessation. Participants recruited through online advertising are randomised to 1
      of 12 cells and serve as 'seed' users. All user interactions are tracked,
      including social interactions with friends. Individuals installing the
      application that can be traced back to a seed participant are deemed
      'descendants' and form the outcome of interest. Analysis will be conducted using
      Poisson regression, with event count as the outcome and the number of seeds in
      the cell as the exposure. RESULTS: The results will be reported as a baseline R0
      for the reference group, and incidence rate ratio for the remainder of
      predictors. ETHICS AND DISSEMINATION: This study uses an abbreviated consent
      process designed to minimise barriers to adoption and was deemed to be minimal
      risk by the Institutional Review Board (IRB). Results will be disseminated
      through traditional academic literature as well as social media. If feasible,
      anonymised data and underlying source code are intended to be made available
      under an open source license. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT01746472.

PMID- 24448848
TI  - Developing a complex intervention to improve prescribing safety in primary care:
      mixed methods feasibility and optimisation pilot study.
AB  - OBJECTIVES: (A) To measure the extent to which different candidate outcome
      measures identified high-risk prescribing that is potentially changeable by the
      data-driven quality improvement in primary care (DQIP) intervention.(B) To
      explore the value of reviewing identified high-risk prescribing to clinicians.(C)
      To optimise the components of the DQIP intervention. DESIGN: Mixed method study.
      SETTING: General practices in two Scottish Health boards. PARTICIPANTS: 4
      purposively sampled general practices of varying size and socioeconomic
      deprivation. OUTCOME MEASURES: Prescribing measures targeting (1) high-risk use
      of the non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelets; (2)
      'Asthma control' and (3) 'Antithrombotics in atrial fibrillation (AF)'.
      INTERVENTION: The prescribing measures were used to identify patients for review
      by general practices. The ability of the measures to identify potentially
      changeable high-risk prescribing was measured as the proportion of patients
      reviewed where practices identified a need for action. Field notes were recorded
      from meetings between researchers and staff and key staff participated in
      semistructured interviews exploring their experience of the piloted intervention
      processes. RESULTS: Practices identified a need for action in 68%, 25% and 18% of
      patients reviewed for prescribing measures (1), (2) and (3), respectively.
      General practitioners valued being prompted to review patients, and perceived
      that (1) 'NSAID and antiplatelet' and (2) 'antithrombotics in AF' were the most
      important to act on. Barriers to initial and ongoing engagement and to sustaining
      improvements in prescribing were identified. CONCLUSIONS: 'NSAIDs and
      antiplatelets' measures were selected as the most suitable outcome measures for
      the DQIP trial, based on evidence of this prescribing being more easily
      changeable. In response to the barriers identified, the intervention was designed
      to include a financial incentive, additional ongoing feedback on progress and
      reprompting review of patients, whose high-risk prescribing was restarted after a
      decision to stop. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT01425502.

PMID- 24448849
TI  - SBAR improves communication and safety climate and decreases incident reports due
      to communication errors in an anaesthetic clinic: a prospective intervention
      study.
AB  - OBJECTIVES: We aimed to examine staff members' perceptions of communication
      within and between different professions, safety attitudes and psychological
      empowerment, prior to and after implementation of the communication tool
      Situation-Background-Assessment-Recommendation (SBAR) at an anaesthetic clinic.
      The aim was also to study whether there was any change in the proportion of
      incident reports caused by communication errors. DESIGN: A prospective
      intervention study with comparison group using preassessments and
      postassessments. Questionnaire data were collected from staff in an intervention
      (n=100) and a comparison group (n=69) at the anaesthetic clinic in two hospitals
      prior to (2011) and after (2012) implementation of SBAR. The proportion of
      incident reports due to communication errors was calculated during a 1-year
      period prior to and after implementation. SETTING: Anaesthetic clinics at two
      hospitals in Sweden. PARTICIPANTS: All licensed practical nurses, registered
      nurses and physicians working in the operating theatres, intensive care units and
      postanaesthesia care units at anaesthetic clinics in two hospitals were invited
      to participate. INTERVENTION: Implementation of SBAR in an anaesthetic clinic.
      PRIMARY AND SECONDARY OUTCOMES: The primary outcomes were staff members'
      perception of communication within and between different professions, as well as
      their perceptions of safety attitudes. Secondary outcomes were psychological
      empowerment and incident reports due to error of communication. RESULTS: In the
      intervention group, there were statistically significant improvements in the
      factors 'Between-group communication accuracy' (p=0.039) and 'Safety climate'
      (p=0.011). The proportion of incident reports due to communication errors
      decreased significantly (p<0.0001) in the intervention group, from 31% to 11%.
      CONCLUSIONS: Implementing the communication tool SBAR in anaesthetic clinics was
      associated with improvement in staff members' perception of communication between
      professionals and their perception of the safety climate as well as with a
      decreased proportion of incident reports related to communication errors. TRIAL
      REGISTRATION: ISRCTN37251313.

PMID- 24448850
TI  - Effects of a school-based prevention programme on smoking in early adolescence: a
      6-month follow-up of the 'Eigenstandig werden' cluster randomised trial.
AB  - OBJECTIVES: To test the effects of a school-based prevention programme on
      students' smoking-related behaviour, attitudes and knowledge 6 months after
      implementation over 2 school-years has ended. DESIGN: Two-arm prospective cluster
      randomised controlled trial with a follow-up survey 6 months after end of
      programme implementation, that is, 26 months after baseline. SETTING: 45 public
      secondary schools from four federal states in Germany (Bremen, Hesse, North Rhine
      Westphalia, Schleswig-Holstein). PARTICIPANTS: A total of 3444 students from 172
      classes with a mean age of 10.37 years (SD=0.59) and 47.9% girls at baseline.
      Analysis sample with follow-up up data merged to baseline data comprises 2513
      datasets (73%). INTERVENTION: 'Eigenstandig werden 5+6', a school-based
      prevention programme for grades 5 and 6 to enhance substance-specific and general
      life skills, consisting of 14 units (a 90 min) and two workshops (4-6 h) being
      taught over a time period of 2 school-years by trained teachers. OUTCOME
      MEASURES: Lifetime and current smoking, incidence of smoking in baseline never
      smokers, smoking-related knowledge, attitudes, perceived norms of smoking and
      self-efficacy to refuse cigarette offers were assessed in students. RESULTS: 6
      months after the end of programme implementation, students of intervention
      classes showed significantly lower rates for lifetime smoking (adjusted OR=0.63;
      95% CI 0.41 to 0.96; p=0.026) and incidence of smoking (adjusted OR=0.66; 95% CI
      0.43 to 1.00; p=0.047), a higher increase of smoking-related knowledge (adjusted
      beta=9.38; 95% CI 6.73 to 12.04; p<0.001) and a greater change in attitudes
      towards a more critical perception of risks and disadvantages of smoking
      (adjusted beta=0.10; 95% CI 0.03 to 0.16; p=0.002). No group differences were
      found for current smoking, perceived norms of smoking and self-efficacy to refuse
      cigarette offers. CONCLUSIONS: Participation in the school-based prevention
      programme 'Eigenstandig werden 5+6' may have small effects on smoking behaviour
      and attitudes and a moderate effect on smoking-related knowledge. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN99442407.

PMID- 24448851
TI  - [Emergence of W135 meningococcal serogroup in Chile during 2012].
AB  - The epidemiologic behavior of the Invasive Meningococcal Disease (IMD) in Chile
      has changed. At the end of 2011, the W135 serogroup belonging to the
      hypervirulent clone ST-11 emerged. It affected diverse countries of the world,
      after the Mecca pilgrimage in 2000. In Chile, there have been 133 IMD cases
      during 2012. These figures represent an incidence of 0.7 per 100,000 inhabitants,
      which is 30% higher than expected. Eighty eight percent of cases were confirmed
      by the National Reference Laboratory at the Chilean Public Health Institute. The
      serogroup was determined in 103 strains and 58% belonged to the W135 serogroup,
      surpassing for the first time the B serogroup (37%). The Metropolitan Region
      concentrated 80% of these cases, and the remaining 20% affected other seven
      regions of the country. Forty seven percent of cases corresponded to children
      less than 5 years of age. The predominant clinical presentation of the W135
      serogroup was a sepsis in 67% of cases. The fatality ratio of IDM during 2012 was
      27%, the highest in the past 20 years. With this information, the Chilean
      Ministry of Health decreed a sanitary alert and implemented an integrated
      approach to control and prevent W-135 IDM, denominated "W-135 Action Plan". 

PMID- 24448852
TI  - [Cardiac resynchronization therapy in patients with heart failure: a 10-year
      experience].
AB  - BACKGROUND: Multiple randomized trials support the clinical benefits of cardiac
      resynchronization therapy (CRT) in patients with heart failure (HF) and
      ventricular dyssynchrony. Since the year 2000 this therapy has been increasingly
      used in Chile. AIM: To describe the clinical characteristics and follow-up of HF
      patients undergoing CRT in a single Chilean university hospital during the last
      10 years. PATIENTS AND METHODS: All patients undergoing CRT between 2000 and 2010
      in our university hospital were included. Clinical and echocardiographic data
      were extracted from medical records and mortality causes were obtained from the
      National Identification Service. RESULTS: A total of 252 patients underwent CRT
      during the study period. Seventy five percent were in New York Heart Associatin
      (NYHA) functional class III and mean ejection fraction was 29 +/- 10%. Complete
      left bundle branch block was present in 55% and 20% had permanent atrial
      fibrillation (AF). Mean survival was 86% at 1 year and 82% of patients in NYHA
      class III-IV improved at least one functional class. Survival was poorer in
      patients with ischemic etiology (hazard ratio (HR) 1.48), functional class IV (HR
      2.2), right bundle branch block (RBBB) (HR 3.1) and AF (HR 3.4). No survival
      differences were observed between patients with and without an implanted
      cardiodefibrillator. CONCLUSIONS: This series show good clinical outcomes,
      comparable to those reported in randomized trials. Predictors of worse survival
      included an ischemic etiology, functional class IV, RBBB and AF. Patients with a
      defibrillator had no better survival, which could be relevant in countries with
      limited health care resources.

PMID- 24448853
TI  - [Universal health coverage and accomplishment of secondary prevention goals among
      patients with acute myocardial infarction].
AB  - BACKGROUND: In 2005, acute myocardial infarction (AMI) was included in a
      universal health plan (GES) to reduce inequity in care and optimize its diagnosis
      and treatment. AIM: To evaluate the effect of GES in risk factor control and
      therapeutic management among patients with AMI. MATERIAL AND METHODS: A survey
      was conducted in 2008-2009 in six public hospitals. Patients were identified from
      a hospital based registry of AMI and evaluated one year later with laboratory
      tests and an interview. RESULTS: The registry enrolled 534 patients with ST and
      non ST segment elevation myocardial infarction. Of these, 416 patients aged 63 +/
      12 years (25% women) were evaluated one year later. Eighty three percent were
      evaluated by a cardiologist and 37% by a general practitioner. Twenty two percent
      were evaluated by a nurse and 22% by a nutritionist. At the moment of the
      interview, 9% smoked, 78% were overweight or obese, 24% performed moderate or
      vigorous physical activity >= 150 min/week, 60% had systolic pressure > 130 mmHg
      and 63% a diastolic pressure > 80 mmHg. In 30%, LDL cholesterol was > 100 mg/dl
      and in 43%, triglycerides were > 150 mm/dl. Twenty two percent were diabetic and
      among them, 52% had a glycosylated hemoglobin > 7%. Forty five percent of non
      diabetic patients had a fasting glucose > 100 mg/dl. Ninety three percent were in
      treatment with aspirin, 86% with statins, 66% with b-blockers, and 73% with
      angiotensin converting enzyme inhibitors or angiotensin receptor blockers and 20%
      with clopidogrel. CONCLUSIONS: Despite the high proportion of patients in
      treatment with evidence-based therapy, many do not achieve the targets for risk
      factor control with the new health care model.

PMID- 24448854
TI  - [Obesity and cancer in Chile: estimation of population attributable fractions].
AB  - BACKGROUND: Obesity is a risk factor for the development of certain types of
      cancer. AIM: To estimate the proportion of cancers potentially attributable to
      obesity in men and women in Chile based on the calculation of population
      attributable fractions (PAF %). MATERIAL AND METHODS: Cancer sites studied were
      those where obesity is a known risk factor based on the updated World Cancer
      Research Fund (WCRF) analysis. Namely, colorectal, endometrium, esophagus,
      breast, pancreas, kidney and gallbladder cancers were analyzed. Overall and
      specific PAFs% were calculated for cancer sites and sex from known estimates of
      relative risk and national prevalence of overweight and obesity. RESULTS: The
      overall estimates of cancer PAF% for obesity were approximately 20%, without
      differences between men and women. Highest cancer PAFs% were for endometrial
      (47%) in women, and esophageal (35%) and pancreatic (31%) in men. The largest sex
      differences in PAFs% were for gallbladder (higher in women) and colorectal
      (higher in men). Results are closer to those reported from developed countries
      (USA and United Kingdom) than those from developing countries (Brasil, China).
      CONCLUSIONS: In Chile about 20% of all cancers could be prevented by obesity
      prevention and control strategies.

PMID- 24448855
TI  - [Deterioration of kidney function as a risk factor for mortality among patients
      hospitalized for heart failure].
AB  - BACKGROUND: Acute deterioration of kidney function among patients admitted to the
      hospital for cardiac failure is associated with an increased mortality. AIM: To
      investigate the association between deterioration of kidney function and
      mortality among patients hospitalized for cardiac failure. MATERIAL AND METHODS:
      Patients admitted for decompensated cardiac failure to 14 Chilean hospitals
      between 2002 and 2009 were incorporated to the study. Clinical and laboratory
      features were registered. Serum creatinine values on admission and discharge were
      determined. Hospital and long term mortality was determined requesting death
      certificates to the National Identification Service at the end of follow up,
      lasting 635 +/- 581 days. RESULTS: One thousand sixty four patients were
      incorporated and 1100, aged 68 +/- 13 years (45% females) had information about
      renal function. Seventy seven percent were hypertensive and 36% were diabetic.
      Mean ejection fraction was 41 +/- 18% and 34% had an ejection fraction over 50%.
      Mean admission creatinine was 1.7 +/- 1.6 mg/dl and 19% had a creatinine over 2
      mg/dl. Serum creatinine increased more than 0.5 mg/dl during hospitalization in
      9% of general patients and in 11% of diabetics. The increase in creatinine was
      associated with a higher risk of hospital mortality (odds ratio (OR) 12.9, 95%
      confidence intervals (CI) 6.7-27.6) and long term mortality (OR 2.1, 95% CI 1.6
      3). CONCLUSIONS: The deterioration of renal function during hospitalization of
      patients with heart failure is a risk factor for hospital and long term
      mortality.

PMID- 24448857
TI  - [Weight of specific domains on the overall quality of life according to the
      assessment of participants].
AB  - BACKGROUND: Usually quality of life self-reports are standard and consider that
      all the areas evaluated are equally important. AIM: To explore the influence of
      specific domains on the overall quality of life self-assessment. MATERIAL AND
      METHODS: The brief version of the quality of life questionnaire developed by the
      World Health Organization (WHOQoL bref) was applied to 1229 participants aged 19
      to 60 years (53% women). The questionnaire explores four domains: physical and
      psychological health, social relationships and environment. At the end of each
      domain a new question asking the participant to assess the importance of the
      domain, using a scale of 1 (not important) to 5 (very important), was added. The
      analysis of data considered the assessment of the importance of each domain made
      by participants. The weight of each domain was analyzed using regression
      equations. RESULTS: The physical health had the best evaluation followed by the
      social domain. The environmental domain received the lower evaluation. Among
      women, social domain was the best evaluated domain and among men, the physical
      health domain. According to participants, physical and psychological health had
      the higher weight. The environmental domain had the higher weight on the overall
      assessment of quality of life. CONCLUSIONS: According to participants, physical
      and psychological health are the most important aspects that influence overall
      quality of life.

PMID- 24448856
TI  - [Pregnancy during dialysis: experience in six patients].
AB  - BACKGROUND: The frequency of pregnancies during dialysis is increasing. This
      condition requires changes in the dialysis schedule and nutritional approach.
      AIM: To report the experience in six patients with terminal kidney disease who
      became pregnant. MATERIAL AND METHODS: Retrospective review of medical records of
      women with terminal kidney disease in dialysis who became pregnant in a period of
      27 years. RESULTS: We recorded six successful pregnancies among women in
      hemodialysis treatment aged 32 +/- 4 years. The mean dialysis-time per week was
      19.5 +/- 2.7 hours and Kt/V was 1.55 +/- 0.17. The mean systolic blood pressure
      was 130 +/- 13.3 mmHg. The mean packed cell volume of the group increased from
      22.7% during pre-gestational stage to 30.2% during third trimester of pregnancy.
      All patients received an intensive treatment for anemia. The most common symptom
      of pregnancy was hyperemesis. The mean gestational age (GA) at diagnosis was 13.4
      +/- 4.7 weeks. All patients had preterm deliveries at a GA of 33 +/- 1.7 weeks,
      and 66% of offspring were appropriate for gestational age. CONCLUSIONS: A
      multidisciplinary approach allows high rate of successful pregnancies during
      hemodialysis.

PMID- 24448858
TI  - [Effects of hydroxychloroquine on insulin sensitivity and lipid profile in
      patients with rheumatoid arthritis].
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with a decrease in insulin
      sensitivity (IS), which has been identified as an independent risk factor for the
      development of early atherosclerosis. Hydroxychloroquine (HCQ) may have
      beneficial effects on glucose homeostasis and lipid profile. AIM: To assess the
      effect of HCQ on IS and lipid profile in patients with RA. MATERIAL AND METHODS:
      An open clinical trial was performed in 15 patients aged between 35 and 56 years.
      During three months, patients received 400 mg/day of HCQ orally. Before and after
      the pharmacological intervention, demographic and anthropometric variables, serum
      glucose, total cholesterol (TC), triglycerides (TG), HDL-cholesterol, LDL
      cholesterol, VLDL-cholesterol, insulin and uric acid were measured. IS was
      estimated as the rate of glucose clearance per minute obtained with the insulin
      tolerance test (KITT). RESULTS: Baseline and final KITT values were 4.3 +/- 1.2
      and 4.80 +/- 1.1%/min, respectively (p = 0.03). Significant reductions in serum
      TC (p = 0.04) and TG (p = 0.01) were also observed. No other significant
      differences were observed. CONCLUSIONS: Oral administration of 400 mg/day of HCQ
      during three months in RA patients is associated with an improvement in IS, TC
      and TG.

PMID- 24448859
TI  - [Carotid intima media thickness and C reactive protein among overweight or obese
      subjects without metabolic syndrome].
AB  - BACKGROUND: Recognizing cardiovascular risk in overweight adults is challenging,
      as they usually have a low Framingham risk score (FRAM). In these subjects, non
      traditional biomarkers could improve risk stratification. AIM: To assess carotid
      intima media thickness (CIMT) and ultrasensitive C-reactive protein (usCRP) among
      overweight and obese subjects without metabolic syndrome (MetSyn). SUBJECTS AND
      METHODS: In 1558 asymptomatic participants (816 women, 45 +/- 11 years) we
      measured body mass index (BMI), waist circumference, blood pressure, lipid
      profile, blood glucose, FRAM, usCRP and CIMT. For analytical purposes, we divided
      the subjects in three groups according to BMI and number of ATPIII-MetSyn risk
      factors (RF): 1) BMI < 25 and < 3RF, 2) BMI >= 25 and < 3RF and 3) BMI >= 25 and
      >= 3RF. RESULTS: Participants of group 2 (BMI >= 25 and < 3RF) had a low FRAM
      (8%). Compared with participants of group 1, they had a higher CIMT (0.61 +/- 0.1
      and 0.57 +/- 0.09 mm, respectively, p < 0.01) and usCRP (2.1 +/- 2.1 and 1.5 +/-
      1.9 mg/L respectively, p < 0.01). CONCLUSIONS: This study shows that although
      subjects with overweight/obesity without MetSyn have low cardiovascular risk
      based on FRAM, they have higher CIMT and usCRP than their normal weight
      counterparts.

PMID- 24448860
TI  - [Bioethical challenges of stem cell tourism].
AB  - Stem cells have drawn extraordinary attention from scientists and the general
      public due to their potential to generate effective therapies for incurable
      diseases. At the same time, the production of embryonic stem cells involves a
      serious ethical issue concerning the destruction of human embryos. Although adult
      stem cells and induced pluripotential cells do not pose this ethical objection,
      there are other bioethical challenges common to all types of stem cells related
      particularly to the clinical use of stem cells. Their clinical use should be
      based on clinical trials, and in special situations, medical innovation, both of
      which have particular ethical dimensions. The media has raised unfounded
      expectations in patients and the public about the real clinical benefits of stem
      cells. At the same time, the number of unregulated clinics is increasing around
      the world, making direct offers through Internet of unproven stem cell therapies
      that attract desperate patients that have not found solutions in standard
      medicine. This is what is called stem cells tourism. This article reviews this
      situation, its consequences and the need for international cooperation to
      establish effective regulations to prevent the exploitation of patients and to
      endanger the prestige of legitimate stem cell research. 

PMID- 24448861
TI  - [New alternatives for the treatment of antiphospholipid syndrome. A literature
      review].
AB  - For years the mainstay of antiphospholipid syndrome treatment has been
      anticoagulation and antiplatelet therapy, but the autoimmune nature of the
      disease, and complications of these therapies, created the need to develop new
      therapeutic strategies. New therapeutic alternatives inhibit at different levels,
      the cascade of events leading to the pro-thrombotic state characteristic of the
      antiphospholipid syndrome. We conducted a literature review of these new
      treatments, focusing on the pathophysiological bases that support them and their
      possible clinical applications. 

PMID- 24448862
TI  - [Revista Medica de Chile in the year 2012].
AB  - During the year 2012, 539 manuscripts were submitted to this journal, following
      an increasing trend in the recent decade. Rejection rate was 33%. This higher
      number of submissions demanded a larger number and wider scope of external
      reviews, retarding the editorial process. The mean time lapse from reception to
      acceptance (or rejection) was 6.3 months (range 2-14) and from acceptance to
      publication 5.3 months (range 3-7). Research articles were 43.9% of published
      manuscripts and the remaining articles were Reviews, Special Articles, Case
      Reports, articles on Medical Ethics, Medical Education, Evidence Based Medicine,
      Public Health, History of Medicine, Letters to the Editor and others. Thirty
      seven published manuscripts (14.6%) came from foreign countries and 9 of them
      were published with full text in English. The 2012 Impact Factor was 0.360,
      showing little variation from previous years, locating the journal in the upper
      part of quartil 4 in the ISI-JCR category "Medicine, General and Internal", while
      the SCImago Journal & Country Rank locates the Revista in quartil 2 of its
      category "Medicine (miscellaneous)". In contrast with the low citation rate, the
      number of visits to the open access electronic version in www.scielo.cl averages
      over 3 million visits per year, illustrating that the interest among readers
      outnumbers the country's expectable readership. Only 22% of articles declared to
      have received financial help from entities external to the institution where the
      work was performed, coming mainly from Chilean Governmental competitive funds.
      The aim of Revista Medica de Chile is to provide readers and authors a valuable
      source of information about current relevant topics in general and internal
      medicine, progress in related specialties and updates in basic sciences,
      rendering them available to Health professionals in Chile and worldwide,
      following international standards of ethical and scientific quality in medical
      publications. 

PMID- 24448863
TI  - [Universal screening program and early intervention (USPEI) in congenital
      bilateral sensorineural hearing loss in Chile].
AB  - Congenital hearing loss is the total or partial inability to hear sounds through
      the ears. It is the most common disability in newborns in Chile and worldwide,
      and is a permanent condition. The direct impact on children who are not
      adequately diagnosed is the alteration in acquisition of language and cognitive
      skills and a decline in their social and school insertion, jeopardizing their
      professional and potentially productive life. Universal screening programs for
      hearing loss are essential for the diagnosis, since 50% of infants with hearing
      loss have no known risk factor. Screening before one month of age, confirmation
      before 3 months, and effective intervention before 6 months, allows the
      development of these children as if they had normal hearing. In Chile there is a
      selective program of screening for infants aged less than 32 weeks or 1,500
      grams, as part of Explicit Health Guarantees, but it covers only 0.9% of newborns
      per year. Therefore, a large majority of children remain without diagnosis. The
      aim of this review is to compare the situation in Chile with other countries,
      raising the need to move towards a universal neonatal hearing loss screening
      program, and propose necessary conditions in terms of justification and
      implementation of a universal screening public policy. 

PMID- 24448864
TI  - [Allogenic hematopoietic stem cell transplantation with unrelated cord blood:
      report of three cases from the Chilean cord blood bank].
AB  - Public cord blood banks are a source of hematopoietic stem cells for patients
      with hematological diseases who lack a family donor and need allogeneic
      transplantation. In June 2007 we started a cord blood bank with units donated in
      three maternity wards in Santiago, Chile. We report the first three transplants
      done with cord blood units form this bank. Cord blood units were obtained by
      intrauterine collection at delivery. They were depleted of plasma and red cells
      and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell
      content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six
      hundred cord blood units were stored by March 2012. Three patients received
      allogeneic transplant with cord blood from our bank, two with high risk
      lymphoblastic leukemia and one with severe congenital anemia. They received
      conditioning regimens according to their disease and usual supportive care for
      unrelated donor transplantation until full hematopoietic and immune
      reconstitution was achieved. The three patients had early engraftment of
      neutrophils and platelets. The child corrected his anemia and the leukemia
      patients remain in complete remission. The post-transplant course was complicated
      with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are
      fully functional 24 and 33 months after transplant, the third is still receiving
      immunosuppression. 

PMID- 24448865
TI  - Neurofibromatosis type I and anti-phospholipid antibody syndrome: report of one
      case.
AB  - Neurofibromatosis type I (NF1) has been only rarely reported in association with
      anti-phospholipid syndrome (APS). We report a 38 year-old female with NF1, who
      developed a cervix carcinoma at the age of 30 years and was successfully treated
      with conization, without requiring chemotherapy or radiation. She experienced two
      miscarriages prior to the diagnosis of the carcinoma. When she was 38 years old,
      an APS was diagnosed based on repeatedly positive lupus anticoagulant tests. The
      patient continued to smoke and using oral contraceptives. At 38 years of age she
      had a myocardial infarction, despite the use of oral anticoagulation. She
      required coronary stenting. Aspirin and clopidogrel were indicated thereafter.

PMID- 24448866
TI  - [Renal biopsies during the second trimester of pregnancy: report of two cases].
AB  - Kidney biopsies were performed in two women during their 21st and 24th week of
      pregnancy. The first patient developed an abrupt nephrotic syndrome without
      hypertension or kidney failure. The pathological study disclosed diffuse podocyte
      alterations such as those observed in focal and segmental glomerulosclerosis,
      which had a good response to steroidal treatment. The second patient had a
      progressive renal failure associated with non-nephrotic proteinuria. The biopsy
      disclosed a fibrillary glomerulopathy.

PMID- 24448867
TI  - [Charles Miller Fisher: a giant of neurology].
AB  - C. Miller Fisher MD, one of the great neurologists in the 20th century, died in
      April 2012. Born in Canada, he studied medicine at the University of Toronto. As
      a Canadian Navy medical doctor he participated in World War II and was a war
      prisoner from 1941 to 1944. He did a residency in neurology at the Montreal
      Neurological Institute between 1946 and 1948, and later on was a Fellow in
      Neurology and Neuropathology at the Boston City Hospital. In 1954 he entered the
      Massachusetts General Hospital as a neurologist and neuropathologist, where he
      remained until his retirement, in 2005. His academic career ended as Professor
      Emeritus at Harvard University. His area of special interest in neurology was
      cerebrovascular disease (CVD). In 1954 he created the first Vascular Neurology
      service in the world and trained many leading neurologists on this field. His
      scientific contributions are present in more than 250 publications, as journal
      articles and book chapters. Many of his articles, certainly not restricted to
      CVD, were seminal in neurology. Several concepts and terms that he coined are
      currently used in daily clinical practice. The chapters on CVD, in seven
      consecutive editions of Harrison's Internal Medicine textbook, are among his
      highlights. His death was deeply felt by the neurological community.

PMID- 24448868
TI  - [Cutaneous furuncular myasis caused by Dermatobia hominis].

PMID- 24448869
TI  - [Validation in Chile of Zarit scale caregiver burden, full and short versions:
      correction].

PMID- 24448870
TI  - [Response to letter: original and abbreviated Zarit caregiver burden scales
      validation in Chile].

PMID- 24448871
TI  - [Adherence to treatment in epilepsy: still an unresolved issue].

PMID- 24448874
TI  - Solubility-limited extrinsic n-type doping of a high electron mobility polymer
      for thermoelectric applications.
AB  - The thermoelectric properties of a highperformance electron-conducting polymer,
      (P(NDIOD-T2), extrinsically doped with dihydro-1H-benzoimidazol-2-yl (NDBI)
      derivatives, are reported. The highest thermoelectric power factor that has been
      reported for a solution-processed n-type polymer is achieved; and it is concluded
      that engineering polymerdopant miscibility is essential for the development of
      organic thermoelectrics. 

PMID- 24448873
TI  - Arterio-vena caval fistula detected by monitoring of transpulmonary
      thermodilution curves.

PMID- 24448876
TI  - Are there gender differences in longitudinal patterns of functioning in Nigerian
      stroke survivors during the first year after stroke?
AB  - BACKGROUND: Several studies have examined gender differences in various stroke
      outcomes. There is however little information on the influence of gender on post
      stroke functioning in the context of the International Classification of
      Functioning, Disability and Health (ICF). OBJECTIVE: Gender differences in
      selected components of functioning, namely motor performance (body function),
      activity and participation, were examined in a sample of Nigerian stroke
      survivors. METHODS: This longitudinal study involved consenting first-incidence
      stroke survivors who were consecutively recruited from in-patient wards of a
      University teaching hospital in northern Nigeria. Demographic and clinical data
      were obtained at recruitment while motor performance, activity and participation
      were assessed at the 1st, 3rd, 6th, 9th and 12th months using the Simplified Fugl
      Meyer scale, the Functional Independence Measure Motor Sub-scale and the London
      Handicap Scale respectively. RESULTS: Participants were thirty-three male (60%)
      and 22 female (40%) stroke survivors who did not significantly differ in age,
      stroke sub-type, laterality and initial severity (P > 0.05). There were also no
      significant differences in motor performance, activity and participation between
      the male and female stroke survivors across the time points. CONCLUSION: Gender
      differences were not observed in the components of functioning over the first 12
      months post-stroke.

PMID- 24448875
TI  - tst1-positive ST22-MRSA-IVa in healthy Italian preschool children.
AB  - A survey was performed in May 2013 to assess methicillin-resistant Staphylococcus
      aureus (MRSA) nasal colonization in healthy children attending 26 municipal
      daycare centres in Palermo, Italy. Of the 500 children, ten (2 %) tested
      positive. Eight MRSA isolates were tst1-positive ST22-MRSA-IVa, spa t223; the
      other two isolates were identified as ST1-IVa and ST398-V, respectively. tst1
      positive ST22-MRSA, spa t223 has been previously identified only in the Middle
      Eastern area.

PMID- 24448877
TI  - Language outcomes following neurosurgery for brain tumours: a systematic review.
AB  - BACKGROUND: Language function is susceptible to the effects of brain tumours
      during both the tumour growth phase and during neurosurgical resection. AIM: This
      paper aimed to systematically review existing literature to determine the current
      status of knowledge about language outcomes following neurosurgery. METHODS: A
      systematic review was conducted involving a detailed literature search using
      online databases, quality assessment of relevant articles and data extraction.
      RESULTS: Of the 1449 articles retrieved, nine articles satisfied the study
      criteria. Overall, these studies reported variable patterns of language function
      post-surgery, however, there was a trend towards an early post-surgical decline
      in language function that greatly improved by 3 months. The likelihood of
      developing post-surgical communication impairments was influenced by a number of
      factors including pre-operative aphasia and the identification of sub-cortical
      language tracts inside the tumour margin, however, further research is required
      to fully elucidate pertinent predictors. CONCLUSION: These findings have
      implications for rehabilitation programs following brain tumour surgery and
      suggest that there are a number of key gaps warranting further investigation.

PMID- 24448878
TI  - Positive psychology in rehabilitation medicine: a brief report.
AB  - BACKGROUND: The field of positive psychology has grown exponentially within the
      last decade. To date, however, there have been few empirical initiatives to
      clarify the constructs within positive psychology as they relate to
      rehabilitation medicine. Character strengths, and in particular resilience,
      following neurological trauma are clinically observable within rehabilitation
      settings, and greater knowledge of the way in which these factors relate to
      treatment variables may allow for enhanced treatment conceptualization and
      planning. OBJECTIVE: The goal of this study was to explore the relationships
      between positive psychology constructs (character strengths, resilience, and
      positive mood) and rehabilitation-related variables (perceptions of functional
      ability post-injury and beliefs about treatment) within a baseline data set, a
      six-month follow-up data set, and longitudinally across time points. METHODS:
      Pearson correlations and supplementary multiple regression analyses were
      conducted within and across these time points from a starting sample of thirty
      nine individuals with acquired brain injury (ABI) in an outpatient rehabilitation
      program. RESULTS: Positive psychology constructs were related to rehabilitation
      related variables within the baseline data set, within the follow-up data set,
      and longitudinally between baseline positive psychology variables and follow-up
      rehabilitation-related data. CONCLUSIONS: These preliminary findings support
      relationships between character strengths, resilience, and positive mood states
      with perceptions of functional ability and expectations of treatment,
      respectively, which are primary factors in treatment success and quality of life
      outcomes in rehabilitation medicine settings. The results suggest the need for
      more research in this area, with an ultimate goal of incorporating positive
      psychology constructs into rehabilitation conceptualization and treatment
      planning.

PMID- 24448879
TI  - Cartilage differentiation in ependymoma: histogenetic considerations on a new
      case.
AB  - The presence of cartilage in gliomas is a very unusual finding and has been
      mainly reported in ependymomas and in astrocytomas. A derivation of cartilage
      from neuroepithelial cells through a neuroepithelial-mesenchymal transition or
      directly from blood vessel-associated multipotent stromal elements has been
      proposed. We herein describe a further case of ependymoma with the presence of
      cartilage in a child affected by a tumor in the posterior fossa. In this case,
      only the last recurrence, characterized by focal areas of anaplasia, contained a
      nodule of cartilage. The immunohistochemical expression of fibronectin, tenascin
      C, and CD44 was investigated, and the possible role of these molecules in the
      process of cartilage formation is discussed. Moreover, the literature on the
      subject is reviewed. 

PMID- 24448880
TI  - Aquatic environments polluted with antibiotics and heavy metals: a human health
      hazard.
AB  - Aquatic environments often receive wastewater containing pollutants such as
      antibiotics and heavy metals from hospital sewage, as well as contaminants from
      soil. The presence of these pollutants can increase the rate of exchange of
      resistant genes between environmental and pathogenic bacteria, which can make the
      treatment of various types of bacterial infections in humans and animals
      difficult, in addition to causing environmental problems such as ecological risk.
      In this study, two tetracycline-resistant Pseudomonas aeruginosa (EW32 and EW33),
      isolated from aquatic environments close to industries and a hospital in
      southeastern Brazil, were investigated regarding the possible association between
      tetracycline and heavy metal resistance. The isolate EW32 presented a conjugative
      plasmid with coresistance to tetracycline and copper, reinforcing the concern
      that antibiotic resistance by acquisition of plasmids can be induced by the
      selective pressure of heavy metals in the environment. 

PMID- 24448881
TI  - Comparison of phenanthrene biodegradation by free and immobilized cell systems:
      formation of hydroxylated compounds.
AB  - One of the foremost environmental issues having a key role in the feasibility
      study of polycyclic aromatic hydrocarbons (PAHs) biodegradation is the concern of
      the toxicity of the formed intermediate metabolites. In this study,
      biodegradability of phenanthrene (PHE) at initial concentrations of 100-500 ppm
      and its hydroxylated intermediate metabolites (IMs) in aqueous phase were
      investigated using free cells (FC) and immobilized cells (IC) in polyvinyl
      alcohol (PVA) cryogel beads. Results showed that both FC and IC systems were
      capable of complete PHE biodegradation at initial concentrations lower than 250
      ppm after 7 days, though IC system showed a higher PHE removal rate. The maximum
      IM concentrations observed at initial PHE concentrations of 100 and 250 ppm were
      20 and 49 ppm for FC system, whereas 7.4 and 19 ppm were obtained for IC system,
      respectively, and IMs were finally removed after 7 days. Similarly, at 500 ppm,
      IC system resulted in higher removal of PHE compared to FC system. However,
      during the 7-day period for FC system, IMs concentration rose up to 59 ppm, while
      for IC system, IMs concentration reaches a maximum at day 5 and thereafter it
      follows a negative rate. It was also shown that resorcinol as an indicator of
      hydroxylated aromatic metabolites at concentrations of 0-100 ppm can well be
      biodegraded by free and immobilized cell systems. No prohibition on PHE
      biodegradation could hence occur due to IMs formation. Additionally, stability of
      IC system was examined in repeated-batch cultures, showing the effective removal
      of PHE up to nine reuse cycles. 

PMID- 24448882
TI  - Degradation of industrial surfactants by photocatalysis combined with ozonation.
AB  - The efficiency of titanium dioxide-mediated photocatalytic degradation of
      pollutants can be enhanced by combination with another advanced oxidation
      procedure such as ozonation. Mineralization of hydroxy- and
      dihydroxybenzenesulfonate based on these methods, both individually and combined,
      was investigated by monitoring the total organic carbon content, sulfate
      concentration, pH, high-performance liquid chromatography as well as the
      absorption spectral changes. The mineralization efficiency of the combined
      procedure significantly exceeded the sum of those of the individual techniques.
      The comparison of the disappearance of the starting material and the formation of
      the sulfate ions indicates that desulfonation is not the primary step of the
      degradation. Moreover, in the case of the combined method, ring cleavage, and
      thus, partial mineralization can occur without desulfonation. Efficient
      degradation of other, widely used industrial surfactants, such as alkylbenzene
      sulfonates and alkyl ether sulfates, was also achieved by heterogeneous
      photocatalysis combined with ozonation, offering an applicable method for the
      removal of these pollutants.

PMID- 24448883
TI  - An electrochemical nanocomposite modified carbon paste electrode as a sensor for
      simultaneous determination of hydrazine and phenol in water and wastewater
      samples.
AB  - In this study, we report preparation of a high sensitive electrochemical sensor
      for determination of hydrazine in the presence of phenol in water and wastewater
      samples. In the first step, we describe synthesis and characterization of
      ZnO/CNTs nanocomposite with different methods such as transmission electron
      microscopy (TEM) and X-ray diffraction (XRD). In the second step, application of
      the synthesis nanocomposite describes the preparation of carbon paste electrode
      modified with N-(4-hydroxyphenyl)-3,5-dinitrobenzamide as a high sensitive and
      selective voltammetric sensor for determination of hydrazine and phenol in water
      and wastewater samples. The mediated oxidation of hydrazine at the modified
      electrode was investigated by cyclic voltammetry, chronoamperometry, and
      electrochemical impedance spectroscopy (EIS). Also, the values of catalytic rate
      constant (k) and diffusion coefficient (D) for hydrazine were calculated. Square
      wave voltammetry (SWV) of hydrazine at the modified electrode exhibited two
      linear dynamic ranges with a detection limit (3sigma) of 8.0 nmol L(-1). SWV was
      used for simultaneous determination of hydrazine and phenol at the modified
      electrode and quantitation of hydrazine and phenol in some real samples by the
      standard addition method. 

PMID- 24448884
TI  - Indoor air quality (IAQ) assessment in a multistorey shopping mall by high
      spatial-resolution monitoring of volatile organic compounds (VOC).
AB  - In order to assess indoor air quality (IAQ), two 1-week monitoring campaigns of
      volatile organic compounds (VOC) were performed in different areas of a
      multistorey shopping mall. High-spatial-resolution monitoring was conducted at 32
      indoor sites located in two storehouses and in different departments of a
      supermarket. At the same time, VOC concentrations were monitored in the mall and
      parking lot area as well as outdoors. VOC were sampled at 48-h periods using
      diffusive samplers suitable for thermal desorption. The samples were then
      analyzed with gas chromatography-mass spectrometry (GC-MS). The data analysis and
      chromatic maps indicated that the two storehouses had the highest VOC
      concentrations consisting principally of terpenes. These higher TVOC
      concentrations could be a result of the low efficiency of the air exchange and
      intake systems, as well as the large quantity of articles stored in these small
      spaces. Instead, inside the supermarket, the food department was the most
      critical area for VOC concentrations. To identify potential emission sources in
      this department, a continuous VOC analyzer was used. The findings indicated that
      the highest total VOC concentrations were present during cleaning activities and
      that these activities were carried out frequently in the food department. The
      study highlights the importance of conducting both high-spatial-resolution
      monitoring and high-temporal-resolution monitoring. The former was able to
      identify critical issues in environments with a complex emission scenario while
      the latter was useful in interpreting the dynamics of each emission source.

PMID- 24448885
TI  - In vivo optical imaging of folate receptor-beta in head and neck squamous cell
      carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: Folate receptor (FR) expression, although known to be
      elevated in many types of cancer and inflammatory cells, has not been well
      characterized in head and neck squamous cell carcinoma (HNSCC). We hypothesized
      that tumor infiltrating inflammatory cells expressing FR-beta could allow
      fluorescent visualization of HNSCC tumors using folate conjugated dyes even when
      FR expression in cancer cells is low. STUDY DESIGN: Retrospective review of
      clinical pathologic specimens and in vivo animal study. METHODS: A tissue
      microarray with tumor and tumor-free tissue from 22 patients with HNSCC was
      stained with antibodies to FR-alpha and FR-beta. We characterized FR-beta(+)
      cells by examining CD45, CD68, CD206, and transforming growth factor (TGF)-beta
      expression. To investigate fluorescent imaging, mice with orthotopic tumor
      xenografts were imaged in vivo after intravenous injections of folate conjugated
      fluorescein isothiocyanate (folate-FITC) and were histologically evaluated ex
      vivo. RESULTS: All tumor samples demonstrated significant FR-beta staining and
      negligible FR-alpha staining. FR-beta(+) cells found in tumors coexpressed CD68
      and had increased expression of CD206 and TGF-beta characteristic of tumor
      associated macrophages. In the xenograft models, tumors showed strong in vivo
      fluorescence after folate-FITC injection in contrast to surrounding normal
      tissues. Histologic examination of the xenograft tissue similarly showed folate
      FITC uptake in areas of inflammatory cellular infiltrate. CONCLUSIONS: Although
      HNSCC tumor cells do not express FR, HNSCC tumors contain a significant
      population of FR-beta-expressing macrophages. Folate conjugated fluorescent dye
      is able to specifically target and label tumor xenografts to permit macroscopic
      fluorescence imaging due to FR-beta expression on the infiltrating inflammatory
      cells.

PMID- 24448886
TI  - Synthesis of full length and truncated microcin B17 analogues as DNA gyrase
      poisons.
AB  - Microcin B17 (MccB17) is a post-translationally modified peptide containing
      thiazole and oxazole heterocycles that interrupt the peptide backbone. MccB17 is
      capable of poisoning DNA gyrase through stabilization of the gyrase-DNA cleavage
      complex and has therefore attracted significant attention. Using a combination of
      Fmoc-strategy solid-phase peptide synthesis and solution-phase fragment assembly
      we have prepared a library of full-length and truncated MccB17 analogues to
      investigate key structural requirements for gyrase-poisoning activity. Synthetic
      peptides lacking the glycine-rich N-terminal portion of the full-length sequence
      showed strong stabilization of the gyrase-DNA cleavage complex with increased
      potency relative to the full-length sequences. This truncation, however, led to a
      decrease in antibacterial activity of these analogues relative to their full
      length counterparts indicating a potential role of the N-terminal region of the
      natural product for cellular uptake. 

PMID- 24448887
TI  - Synthesis and anticonvulsant activity evaluation of 7-alkoxy[1,2,4]triazolo[3,4
      b]benzothiazol-3(2H)-ones.
AB  - A new series of 7-alkoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-ones were
      synthesized and evaluated for their anticonvulsant activities. Among these
      compounds, 7-propoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4c) and 7
      butoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4d) showed the highest
      activity against maximal electroshock (MES)-induced tonic extension [effective
      dose (ED)50 : 11.4 and 13.6 mg/kg, respectively]. It is worth mentioning that
      compound 4d showed especially low neurotoxicity, which led to a high protective
      index (PI >51). The orally anticonvulsant activity data of compound 4d further
      confirmed its efficacy, in an MES test, and its high safety with a PI value of
      50.2. In addition, the potency of compound 4h against seizures induced by
      pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical
      induced seizure tests suggested that compound 4d may exert its anticonvulsant
      activity through affecting the GABAergic system. 

PMID- 24448888
TI  - Two novel aromatic glucosides, marylaurencinosides D and E, from the fresh
      flowers of Cymbidium Great Flower 'Marylaurencin'.
AB  - Two novel aromatic glucosides, named marylaurencinosides D (1) and E (2), were
      isolated from the fresh flowers of Cymbidium Great Flower 'Marylaurencin'. In
      addition, eight known aromatic compounds (3-10) were isolated. These structures
      were determined on the basis of NMR experiments as well as chemical evidence. 

PMID- 24448889
TI  - Challenging the myth of an "epidemic" of common mental disorders: trends in the
      global prevalence of anxiety and depression between 1990 and 2010.
AB  - BACKGROUND: Anxiety disorders and major depressive disorder (MDD) are common and
      disabling mental disorders. This paper aims to test the hypothesis that common
      mental disorders have become more prevalent over the past two decades. METHODS:
      We conducted a systematic review of prevalence, remission, duration, and excess
      mortality studies for anxiety disorders and MDD and then used a Bayesian meta
      regression approach to estimate point prevalence for 1990, 2005, and 2010. We
      also conducted a post-hoc search for studies that used the General Health
      Questionnaire (GHQ) as a measure of psychological distress and tested for trends
      to present a qualitative comparison of study findings RESULTS: This study found
      no evidence for an increased prevalence of anxiety disorders or MDD. While the
      crude number of cases increased by 36%, this was explained by population growth
      and changing age structures. Point prevalence of anxiety disorders was estimated
      at 3.8% (3.6-4.1%) in 1990 and 4.0% (3.7-4.2%) in 2010. The prevalence of MDD was
      unchanged at 4.4% in 1990 (4.2-4.7%) and 2010 (4.1-4.7%). However, 8 of the 11
      GHQ studies found a significant increase in psychological distress over time.
      CONCLUSIONS: The perceived "epidemic" of common mental disorders is most likely
      explained by the increasing numbers of affected patients driven by increasing
      population sizes. Additional factors that may explain this perception include the
      higher rates of psychological distress as measured using symptom checklists,
      greater public awareness, and the use of terms such as anxiety and depression in
      a context where they do not represent clinical disorders.

PMID- 24448890
TI  - Concise review: a population shift view of cellular reprogramming.
AB  - Cellular reprogramming can offer valuable insight into disease mechanism and has
      the potential to provide novel tools for regenerative medicine. Yet it remains an
      inefficient and often incomplete process. However, experiments show that almost
      all somatic cells eventually give rise to the pluripotent state, albeit at
      different latencies, as long as expression of reprogramming transcription factors
      is maintained. Furthermore, it appears that specific subpopulations of cells can
      be identified that show enhanced propensities to be reprogrammed to the
      pluripotent state. It has been proposed that an initial stochastic process is
      responsible for this initial priming that is followed by a deterministic process
      that directs the primed cells into the pluripotent state. Here, we propose a
      population shift view of cellular reprogramming, which explains these
      observations and reconciles the stochastic and deterministic nature of this
      process. According to this view, a small population of cells, whose states are
      closer to the pluripotent state and reside in pre-existing energetically
      favorable trajectories, will be initially selected for reprogramming. Moreover,
      by maintaining ectopic expression of reprogramming factors, other cells enter
      these pathways as a result of transcriptional and epigenetic stochastic
      variations. Consequently, increasing numbers of cells reach the pluripotent
      state, and the cell population distribution shifts toward this state.
      Importantly, additional perturbations can change the epigenetic landscape,
      allowing cells more access to the reprogramming trajectories, thereby increasing
      reprogramming efficiency. Knowledge of the initial cellular subpopulations and
      pathways of states that lead to the final cellular state should allow us to
      design alternative perturbation strategies to improve reprogramming efficiency
      and fidelity.

PMID- 24448891
TI  - Uterine artery Doppler, birth weight and timing of onset of pre-eclampsia:
      providing insights into the dual etiology of late-onset pre-eclampsia.
AB  - OBJECTIVE: To investigate the relationship between uterine artery Doppler
      ultrasound indices and birth weight in women with early-, intermediate- and late
      onset pre-eclampsia as compared with women with uneventful pregnancy outcome.
      METHODS: In a retrospective, observational cohort study, uterine artery Doppler
      assessment was carried out at 18+0 to 23+6 weeks' gestation in 26,893 women
      attending for routine antenatal care in a tertiary care center. The mean
      resistance index (RI) and its relationship to the outcome of pregnancy and birth
      weight centiles were evaluated. RESULTS: Uterine artery RI showed a significant,
      negative correlation with birth weight (r= -0.20, P<0.0001). Patients with early
      onset pre-eclampsia had an increased prevalence of high uterine artery mean RI,
      above the 90(th) centile, corresponding to an increased proportion of small-for
      gestational age (SGA) neonates with a birth weight below the 10(th) centile. In
      late-onset pre-eclampsia, however, there was an unexpectedly higher proportion of
      large-for-gestational-age (LGA) neonates with a birth weight above the 90(th)
      centile without a concurrent increase in the prevalence of low uterine artery
      mean RI below the 10(th) centile. CONCLUSIONS: The finding of a bimodal skewed
      distribution of birth weight, with neonates exhibiting a higher prevalence of
      both LGA and SGA with late-onset pre-eclampsia, indicates that there are two
      types of late-onset pre-eclampsia. These findings explain the poor performance of
      mid-trimester uterine artery Doppler in predicting pre-eclampsia at term and
      provide insights into the placental origins of the early and late forms of pre
      eclampsia.

PMID- 24448892
TI  - Extended indications of percutaneous endoscopic lavage and drainage for the
      treatment of lumbar infectious spondylitis.
AB  - PURPOSE: The treatment of spinal infection remains a challenge for spinal
      surgeons because of the variable presentations and complicated course. The
      diagnostic and therapeutic value of percutaneous endoscopic lavage and drainage
      (PELD) has been proved in some recent studies. The purpose of this study is to
      evaluate the efficacy of PELD in patients with advanced infectious spondylitis
      which may traditionally require open surgery. METHODS: We retrospectively
      reviewed the medical records of 21 patients who underwent PELD to treat their
      advanced lumbar infectious spondylitis. Patients with severe infection resulting
      in significant neurological deficit and mechanical instability were excluded from
      the PELD procedure, which was only used on selected patients with less severe
      disease. The 21 patients were categorized into three groups based on their past
      history, clinical presentation, and imaging studies: those with paraspinal
      abscesses, postoperative recurrent infection, and multilevel infection. Clinical
      outcomes were assessed by careful physical examination, Odom's criteria, regular
      serologic testing, and imaging studies to determine whether continued
      conservative treatment or surgical intervention was necessary. RESULTS: Causative
      bacteria were identified in 19 (90.5%) of 21 biopsy specimens. Appropriate
      parenteral antibiotics for the predominant pathogen isolated from the infected
      tissue biopsy cultures were prescribed for the patients. All patients reported
      satisfactory recovery and relief of back pain, except three with multilevel
      infections who underwent anterior debridement and fusion within 2 weeks after
      treatment with PELD. The overall infection control rate was 86%. One patient with
      epidural abscess and spondylolytic spondylolisthesis of the L5-S1 received
      instrumented fusion surgery due to mechanical instability 5 months later. No
      surgery-related major complications were found, except 2 patients who had
      transient paraesthesia in the affected lumbar segment. CONCLUSIONS: PELD was
      successful in obtaining a bacteriologic diagnosis, relieving the patient's
      symptoms, and assisting in eradication of lumbar infectious spondylitis. The
      indications of this minimally invasive procedure could be extended to treat
      patients suffering from spinal infections with paraspinal abscesses and
      postoperative recurrent infection. Patients with multilevel infection may have
      trivial benefits from PELD due to poor infection control and mechanical
      instability of the affected segments.

PMID- 24448893
TI  - Sacropelvic fixation versus fusion to the sacrum for spondylodesis in multilevel
      degenerative spine disease.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: For successful multilevel
      correction and stabilization of degenerative spinal deformities, a rigid basal
      construct to the sacrum is indispensable. The primary objective of this study was
      to compare the results of two different sacropelvic fixation techniques to
      conventional stabilization to the sacrum in patients with multilevel degenerative
      spine disease. METHODS: A total of 69 patients with multisegmental fusion surgery
      (mean number of stabilized functional spinal units: 7.0 +/- 3.3) with a minimum
      of 1-year follow-up were included. 32 patients received fixation to the sacrum
      (S1), 23 patients received S1 and iliac screw fixation (iliac) and 14 patients
      were treated with iliosacral plate fixation (plate). Primary outcome parameters
      were radiographic outcome concerning fusion in the segment L5-S1, rate of screw
      loosening, back and buttock pain reduction [numeric rating scale for pain
      evaluation: 0 indicating no pain, 10 indicating the worst pain], overall extent
      of disability after surgery (Oswestry Disability Index) and the number of
      complications. RESULTS: The three groups did not differ in body mass index, ASA
      score, the number of stabilized functional spinal units, duration of surgery, the
      number of previous spine surgeries, or postoperative complication rate. The
      incidence of L5-S1 pseudarthrosis after 1 year in the S1, iliac, and plate groups
      was 19, 0, and 29 %, respectively (p < 0.05 iliac vs. plate). The incidence of
      screw loosening after 1 year in the S1, iliac, and plate groups was 22, 4, and 43
      %, respectively (p < 0.05 iliac vs. plate). Average Oswestry scores after 1 year
      in the S1, iliac, and plate groups were 40 +/- 18, 42 +/- 20, and 58 +/- 18,
      respectively (p < 0.05 both S1 and iliac vs. plate). CONCLUSION: The surgical
      treatment of multilevel degenerative spine disease carries a significant risk for
      pseudarthrosis and screw loosening, mandating a rigid sacropelvic fixation. The
      use of an iliosacral plate resulted in an inferior surgical and clinical outcome
      when compared to iliac screws.

PMID- 24448894
TI  - CoCr rods provide better frontal correction of adolescent idiopathic scoliosis
      treated by all-pedicle screw fixation.
AB  - PURPOSE: Pedicle screw fixation is considered biomechanically advantageous in
      adolescent idiopathic scoliosis (AIS) correction, because it uses as an anchor
      the pedicle, which is the hardest part of the vertebral body. The ability of the
      rod to correct and hold the correction is a key factor in the selection of rod
      material. The goal of this study was to compare the results obtained by stainless
      steel (SS) and cobalt-chromium (CoCr) rods materials for the treatment of AIS
      curves. METHODS: Ninety patients were retrospectively included. Sixty-four
      patients (group 1) were operated on using CoCr rods. Twenty-six patients (group
      2) were operated on using SS rods. All the patients were treated by the same
      surgeon using all-pedicle screw constructs. RESULTS: In group 1, the correction
      was respectively 41.03 degrees  and 35.78 degrees  for main and secondary curves.
      In group 2, the correction was respectively 30.98 degrees  and 24.42 degrees  for
      main and secondary curves. Statistical analysis showed improved correction rates
      in patients operated with CoCr rods for main (P < 0.0001) and secondary (P =
      0.0003) curves with a lower loss of correction at final follow-up. Regarding the
      sagittal profile, postoperative T4T12 thoracic kyphosis was 28.04 degrees  in
      CoCr group compared to 22.79 degrees  in SS group (P = 0. 0.0038). DISCUSSION:
      The present study confirms the ability of the all-pedicle screw construct to
      reach the maximum coronal plane correction and prevent deformity progression
      while maintaining balance. CoCr rods have the ability to exert higher corrective
      forces on the spine with relatively small amounts of rod deformation. Our
      findings confirm that CoCr rods have the ability to produce higher correction
      rates in frontal plane compared to SS rods of the same diameter.

PMID- 24448895
TI  - Answer to the Letter to the Editor of Feng Li et al. entitled "A systematic
      review with meta-analysis of posterior interbody fusion versus posterolateral
      fusion in lumbar spondylolisthesis" by Xiaoyang Liu, Yipeng Wang, Guixing Qiu,
      Xisheng Weng, Bin Yu. Eur Spine J (2013): doi:10.1007/s00586-013-2880-8.

PMID- 24448896
TI  - Comment on Tian et al.: Minimally invasive versus open transforaminal lumbar
      interbody fusion: a meta-analysis based on the current evidence.

PMID- 24448899
TI  - Metabolic syndrome in patients taking clozapine: prevalence and influence of
      catechol-O-methyltransferase genotype.
AB  - RATIONALE: Metabolic syndrome (MetS) has consistently been identified as an
      adverse effect of long-term treatment with atypical antipsychotics (AAPs) such as
      clozapine. Elevated serum homocysteine concentration has been found to act as an
      independent risk factor for MetS, and catechol-O-methyltransferase (COMT)
      catalyzes the homocysteine metabolism. We accordingly hypothesized that COMT
      dysregulation may confer the susceptibility to MetS induced by AAPs, potentially
      in a gender-specific manner, because the interaction effects of COMT and gender
      have been consistently reported. OBJECTIVES: This study aimed at determining the
      prevalence and influence of COMT on MetS among a population undergoing long-term
      clozapine treatment. METHODS: A total of 468 schizophrenia patients taking
      clozapine were divided into two groups, those experiencing MetS and non-MetS. We
      genotyped three functional variants (rs4633, rs4680, and rs4818) in COMT and
      measured the serum levels of fasting homocysteine, glucose, triglyceride (TG),
      and high-density lipoprotein cholesterol. RESULTS: MetS was found in 202/468
      (43.2 %) of all the patients, with 40.2 % prevalence (138/343) in males and 51.2
      % (64/125) in females. Patients with MetS had notably higher metabolic parameters
      than those without MetS. The mean levels of homocysteine in patients with MetS
      were significantly higher than those without MetS. We found a positive
      association between the rs4680 polymorphism and the serum triglyceride levels
      (corrected P = 0.024). Further analysis revealed that the rs4680 Met allele was
      significantly associated with increased triglyceride levels among female patients
      (P = 0.009), but not among males (P = 0.07). CONCLUSIONS: Our findings suggest a
      potential association between rs4680 in COMT and elevated TG levels, particularly
      among female patients.

PMID- 24448898
TI  - History of childhood adversity is positively associated with ventral striatal
      dopamine responses to amphetamine.
AB  - RATIONALE: Childhood exposure to severe or chronic trauma is an important risk
      factor for the later development of adult mental health problems, such as
      substance abuse. Even in nonclinical samples of healthy adults, persons with a
      history of significant childhood adversity seem to experience greater
      psychological distress than those without this history. Evidence from rodent
      studies suggests that early life stress may impair dopamine function in ways that
      increase risks for drug abuse. However, the degree to which these findings
      translate to other species remains unclear. OBJECTIVES: This study was conducted
      to examine associations between childhood adversity and dopamine and subjective
      responses to amphetamine in humans. METHODS: Following intake assessment, 28
      healthy male and female adults, aged 18-29 years, underwent two consecutive 90
      min positron emission tomography studies with high specific activity
      [(11)C]raclopride. The first scan was preceded by intravenous saline; the second
      by amphetamine (AMPH 0.3 mg/kg). RESULTS: Consistent with prior literature,
      findings showed positive associations between childhood trauma and current levels
      of perceived stress. Moreover, greater number of traumatic events and higher
      levels of perceived stress were each associated with higher ventral striatal
      dopamine responses to AMPH. Findings of mediation analyses further showed that a
      portion of the relationship between childhood trauma and dopamine release may be
      mediated by perceived stress. CONCLUSIONS: Overall, results are consistent with
      preclinical findings suggesting that early trauma may lead to enhanced
      sensitivity to psychostimulants and that this mechanism may underlie increased
      vulnerability for drug abuse.

PMID- 24448900
TI  - The effects of age at the onset of drinking to intoxication and chronic ethanol
      self-administration in male rhesus macaques.
AB  - RATIONALE: Consumption of alcohol begins during late adolescence in a majority of
      humans, and the greatest drinking occurs at 18-25 years then decreases with age.
      OBJECTIVES: The present study measured the differences in ethanol intake in
      relation to age at the onset of ethanol access among nonhuman primates to control
      for self-selection in humans and isolate age effects on heavy drinking. METHODS:
      Male rhesus macaques were assigned first access to ethanol during late
      adolescence (n = 8), young adulthood (n = 8), or early middle age (n = 11). The
      monkeys were induced to drink ethanol (4 % w/v in water) in increasing doses
      (water then 0.5, 1.0, 1.5 g/kg ethanol) using a fixed-time (FT) 300-s schedule of
      food delivery, followed by 22 h/day concurrent access to ethanol and water for 12
      months. Age-matched controls consumed isocaloric maltose-dextrin solution yoked
      to the late adolescents expected to be rapidly maturing (n = 4). RESULTS: Young
      adult monkeys had the greatest daily ethanol intake and blood-ethanol
      concentration (BEC). Only late adolescents escalated their intake (ethanol, not
      water) during the second compared to the first 6 months of access. On average,
      plasma testosterone level was consistent with age differences in maturation and
      tended to increase throughout the experiment more for control than ethanol
      drinking adolescent monkeys. CONCLUSIONS: Young adulthood in nonhuman primates
      strongly disposes toward heavy drinking, which is independent of sociocultural
      factors present in humans. Ethanol drinking to intoxication during the critical
      period of late adolescence is associated with escalation to heavy drinking.

PMID- 24448901
TI  - Prospective memory impairment in long-term opiate users.
AB  - RATIONALE: Opiate use is associated with a range of neurological and cognitive
      deficits. However, to date, no studies have assessed whether these cognitive
      deficits extend to the ability to perform intended actions in the future (i.e.
      prospective memory). Reduced ability in this area might be anticipated due to
      impaired executive functions and episodic memory associated with long-term opiate
      use. OBJECTIVES: The main objectives of this study are to assess the performance
      of long-term opiate users on a laboratory measure of prospective memory which
      closely simulates the types of prospective memory tasks encountered in everyday
      life ('Virtual Week') and to investigate the extent to which prospective memory
      performance is related to executive functions and episodic memory ability.
      METHODS: Twenty-six long-term heroin users enrolled in an opiate substitution
      program, and 30 controls with no previous history of drug use were tested on
      Virtual Week. Retrospective memory and executive functions were also assessed.
      RESULTS: Long-term opiate users were significantly impaired on prospective memory
      performance compared with controls (p = 0.002, eta(2) p = 0.17), and these
      deficits did not vary as a function of prospective memory task type (regular,
      irregular, event, time). The findings also suggest that retrospective memory
      difficulties contribute to the prospective memory difficulties seen in opiate
      users (r s  = 0.78, p < 0.001) but that executive dysfunction is less
      influential. CONCLUSIONS: Prospective memory is sensitive to long-term opiate
      use. Importantly, opiate users suffer from generalised deficits in prospective
      memory, regardless of the task demands, which may have significant implications
      for day-to-day functioning. These results may therefore contribute to the
      development of clinical intervention strategies to reduce the negative impact of
      prospective memory failures in daily life.

PMID- 24448902
TI  - Dysregulation of vitamin D metabolism in the brain and myocardium of rats
      following prolonged exposure to dexamethasone.
AB  - RATIONALE: Chronic stress or hypercortisolism may increase the risks of
      depression, cardiac disorders, and osteoporosis, which are also associated with
      vitamin D (VD) deficiency. Both glucocorticoid receptor (GR) and vitamin D
      receptor (VDR) are widely distributed and affect many aspects of human
      physiology. The cross talk between the two steroids is pervasive, but the effect
      of glucocorticoids on circulating VD and local VD metabolism remains elusive.
      OBJECTIVES: To fill this critical gap, we assessed the alterations of circulating
      VD and VD intracrine system in the brain and myocardium of rats treated with two
      different doses (0.2 and 2 mg/kg/day, respectively) of dexamethasone (Dex).
      RESULTS: Daily treatment with 2 mg/kg of Dex for 10 days induced the rats to a
      depressive-like state and decreased the expression of both VDR and the
      cytochromes P450 enzymes involved in VD activation (CYP27B1) and catabolism
      (CYP24A1) in the prefrontal cortex and hippocampus. Meanwhile, the dose of 0.2
      mg/kg Dex increased the expression of VDR in the prefrontal cortex but inhibited
      CYP27B1/CYP24A1/VDR expression in the hippocampus. Similarly, in the myocardium,
      the rats treated with Dex showed significantly lower expression of
      CYP27B1/CYP24A1/VDR. Renal VD metabolism and serum VD status were unchanged in
      0.2 mg/kg Dex-treated rats. However, the higher dose suppressed the three key
      players involved in VD metabolism but did not alter serum VD levels. CONCLUSION:
      These data provide new evidence that glucocorticoids could affect intracrine
      actions of VD in the brain and myocardium, which suggests the potential
      involvement of VD in the neural and cardiac dysfunctions induced by
      glucocorticoid excess.

PMID- 24448903
TI  - The nuclear gamma-H2AX apoptotic ring: implications for cancers and autoimmune
      diseases.
AB  - Apoptosis is a fundamental process for metazoan development. It is also relevant
      to the pathophysiology of immune diseases and cancers and to the outcome of
      cancer chemotherapies, as well as being a target for cancer therapies. Apoptosis
      involves intrinsic pathways typically initiated by DNA damaging agents and
      engaging mitochondria, and extrinsic pathways typically initiated by "death
      receptors" and their ligands TRAIL and TNF at the cell surface. Recently, we
      discovered the apoptotic ring, which microscopically looks like a nuclear annular
      staining early in apoptosis. This ring is, in three-dimensional space, a thick
      intranuclear shell consisting of epigenetic modifications including histone H2AX
      and DNA damage response (DDR) proteins. It excludes the DNA repair factors
      usually associated with gamma-H2AX in the DDR nuclear foci. Here, we summarize
      our knowledge of the apoptotic ring, and discuss its biological and
      pathophysiological relevance, as well as its value as a potential pharmacodynamic
      biomarker for anticancer therapies. 

PMID- 24448905
TI  - Increased leptin by hypoxic-preconditioning promotes autophagy of mesenchymal
      stem cells and protects them from apoptosis.
AB  - Autophagy is the basic catabolic progress involved in cell degradation of
      unnecessary or dysfunctional cellular components. It has been proven that
      autophagy could be utilized for cell survival under stresses. Hypoxic
      preconditioning (HPC) could reduce apoptosis induced by ischemia and
      hypoxia/serum deprivation (H/SD) in bone marrow-derived mesenchymal stem cells
      (BMSCs). Previous studies have shown that both leptin signaling and autophagy
      activation were involved in the protection against apoptosis induced by various
      stress, including ischemia-reperfusion. However, it has never been fully
      understood how leptin was involved in the protective effects conferred by
      autophagy. In the present study, we demonstrated that HPC can induce autophagy in
      BMSCs by increased LC3-II/LC3-I ratio and autophagosome formation. Interestingly,
      similar effects were also observed when BMSCs were pretreated with rapamycin. The
      beneficial effects offered by HPC were absent when BMSCs were incubated with
      autophagy inhibitor, 3-methyladenine (3-MA). In addition, down-regulated leptin
      expression by leptin-shRNA also attenuated HPC-induced autophagy in BMSCs, which
      in turn was associated with increased apoptosis after exposed to sustained H/SD.
      Furthermore, increased AMP-activated protein kinase phosphorylation and decreased
      mammalian target of rapamycin phosphorylation that were observed in HPC-treated
      BMSCs can also be attenuated by down-regulation of leptin expression. Our data
      suggests that leptin has impact on HPC-induced autophagy in BMSCs which confers
      protection against apoptosis under H/SD, possibly through modulating both AMPK
      and mTOR pathway. 

PMID- 24448904
TI  - The role of the CCN family of proteins in female reproduction.
AB  - The CCN family of proteins consists of six high homologous matricellular proteins
      which act predominantly by binding to heparin sulphate proteoglycan and a variety
      of integrins. Interestingly, CCN proteins are regulated by ovarian steroid
      hormones and are able to adapt to changes in oxygen concentration, which is a
      necessary condition for successful implantation. CCN1 is involved in processes of
      angiogenesis within reproductive systems, thereby potentially contributing to
      diseases such as endometriosis and disturbed angiogenesis in the placenta and
      fetus. In the ovary, CCN2 is the key factor for follicular development, ovulation
      and corpora luteal luteolysis, and its deletion leads to fertility defects. CCN1,
      CCN2 and CCN3 seem to be regulators for human trophoblast proliferation and
      migration, but with CCN2 acting as a counterweight. Alterations in the expression
      of these three proteins could contribute to the shallow invasion properties
      observed in preeclampsia. Little is known about the role of CCN4-6 in the
      reproductive organs. The ability of CCN1, CCN2 and CCN3 to interact with numerous
      receptors enables them to adapt their biological function rapidly to the
      continuous remodelling of the reproductive organs and in the development of the
      placenta. The CCN proteins mediate their specific cell physiological function
      through the receptor type of their binding partner followed by a defined
      signalling cascade. Because of their partly overlapping expression patterns, they
      could act in a concert synergistically or in an opposite way within the
      reproductive organs. Imbalances in their expression levels are correlated to
      different human reproductive diseases, such as endometriosis and preeclampsia. 

PMID- 24448906
TI  - CAPE promotes the expansion of human umbilical cord blood-derived hematopoietic
      stem and progenitor cells in vitro.
AB  - Due to the low number of collectable stem cells from single umbilical cord blood
      (UCB) unit, their initial uses were limited to pediatric therapies. Clinical
      applications of UCB hematopoietic stem and progenitor cells (HSPCs) would become
      feasible if there were a culture method that can effectively expand HSPCs while
      maintaining their self-renewal capacity. In recent years, numerous attempts have
      been made to expand human UCB HSPCs in vitro. In this study, we report that
      caffeic acid phenethyl ester (CAPE), a small molecule from honeybee extract, can
      promote in vitro expansion of HSPCs. Treatment with CAPE increased the percentage
      of HSPCs in cultured mononuclear cells. Importantly, culture of CD34(+) HSPCs
      with CAPE resulted in a significant increase in total colony-forming units and
      high proliferative potential colony-forming units. Burst-forming unit-erythroid
      was the mostly affected colony type, which increased more than 3.7-fold in 1 MUg
      mL(-1) CAPE treatment group when compared to the controls. CAPE appears to induce
      HSPC expansion by upregulating the expression of SCF and HIF1-alpha. Our data
      suggest that CAPE may become a potent medium supplement for in vitro HSPC
      expansion. 

PMID- 24448907
TI  - D-ribose, an overlooked player in type 2 diabetes mellitus?

PMID- 24448908
TI  - Reasons reported by African ophthalmologists for staying in Africa and for
      considering migrating.
AB  - In sub-Sahara Africa, the shortage of ophthalmologists is a major obstacle in the
      struggle of fighting preventable blindness. Migration of well-trained
      ophthalmologists has an additional negative effect on the low number of
      caregivers. However, to date, the reasons affecting migration of ophthalmologists
      have not been completely understood. The present study evaluates reasons reported
      by ophthalmologists for staying in their current work setting/country and
      potential reasons why they might consider migrating. In the years 2009-2011,
      after approval was obtained from the Institutional Review Board, a questionnaire
      evaluating reasons for and against migration of ophthalmologists was distributed
      to the participants of 2-week courses in Ethiopia, Cameroon and Kenya providing
      continuing medical education in the field of ophthalmology. A total of 84
      ophthalmologists participated in this survey. The main reasons for staying in
      their current region/country were good working conditions, commitment to help,
      possibility of further training, familial ties and general feeling of
      satisfaction. Professional development elsewhere and better income abroad were
      named as the main reasons for considering migration. Almost half of the survey
      participants reported good infrastructure, equipment, and consumables, which is
      encouraging. Programs aimed at continuing medical education of ophthalmologists
      to enable professional development may have an appropriate role in the
      establishment of an ophthalmic infrastructure which can meet patients' needs. 

PMID- 24448909
TI  - Renal blood flow before and after portosystemic shunt in children with portal
      hypertension.
AB  - INTRODUCTION: Variceal haemorrhage in children with extrahepatic portal
      hypertension is best controlled by an effective decompressive shunt, but long
      term follow up of children who have had splenorenal shunt due to extrahepatic
      portal hypertension (EHPH) gave evidence for assuming the risk of renal venous
      hypertension (RVH). PURPOSE: To study renal hemodynamic before and after portal
      decompression. METHODS: The results of 144 portosystemic shunt operations were
      followed from 2005 to 2013. Seventy-two patients applied central splenorenal
      shunt (CSS) with splenectomy, ten side-to-side splenorenal shunt without
      splenectomy (SRSss), ten patients assessed the distal splenorenal shunt (DSS).
      Forty-three iliacomesenterial anastomosis (IMA) and in nine cases performed
      mesocaval anastomosis (MCA). Children had a standard pre- and postoperative work
      up including gastrointestinal endoscopy, Doppler ultrasonography (US), multi
      slice computed tomography (MSCT) and renography. RESULTS: In 11 (15.2 %) patients
      after CSS on duplex, Doppler study revealed signs of impeded venous outflow on
      the left renal vein (LRV). At long-term follow-up PI and RI of left renal artery
      remained at high numbers (1.48 +/- 0.17 and 0.72 +/- 0.19, p <= 0.05,
      respectively) after the CSS. Venous blood flow in the LRV at the hilum showed
      slower speed performance in groups of CSS and after IMA. After DSS, these signs
      have not been detected. Four patients after IMA on US Doppler and CT angiography
      revealed dilated left testicular and ovarian veins, with retrograde blood flow in
      them, which clinically manifested as left flank pain, macro- and microhematuria,
      varicocele and ovaricocele. CONCLUSION: The study shows that CSS and IMA more
      negatively effect on hemodynamics of left kidney and symptoms of RVH obviously
      due to shunting the large amounts of blood from a system of high pressure to a
      low.

PMID- 24448910
TI  - The evaluation of the validity of Alvarado, Eskelinen, Lintula and Ohmann scoring
      systems in diagnosing acute appendicitis in children.
AB  - PURPOSE: To show whether Alvarado, Eskelinen, Lintula and Ohmann scoring systems
      have predictive values in diagnosing acute appendicitis in children. METHODS:
      Sixty patients with suspected acute appendicitis were prospectively evaluated.
      Alvarado, Eskelinen, Lintula and Ohmann scores were calculated separately for
      each patient at the time of admission. The specificity, sensitivity, positive and
      negative predictive values of the scores were calculated. The predictive value of
      the scores was evaluated with the receiver operating characteristic (ROC) curve
      and the consistency among the scores by Kappa test. RESULTS: Twenty of the
      patients were female (33.3 %). The mean age of the patients was 9.9 years (3-16
      years). Forty two patients were operated and appendectomies were performed with
      the diagnosis of acute appendicitis. The area under the ROC curve showed that the
      scores had no predictive value in diagnosing acute appendicitis. Kappa test
      showed that agreement between the scores was not good. CONCLUSION: The
      sensitivity and specificity of the four scoring systems were not sufficient
      enough in diagnosing acute appendicitis in our patient group. We concluded that
      the most important factor affecting the decision for surgery in suspected acute
      appendicitis is the surgeon's experience combined with physical findings of
      repeated clinical examinations.

PMID- 24448911
TI  - Endoscopic correction of complex cases of vesicoureteral reflux utilizing Vantris
      as a new non-biodegradable tissue-augmenting substance.
AB  - PURPOSE: We aimed to evaluate prospectively the efficacy of Vantris as a new non
      biodegradable tissue-augmenting substance in children with complex cases of VUR.
      MATERIALS AND METHODS: Over the last 4 years, 37 children (28 female and 9 male)
      with a mean age of 5.8 +/- 3.1 years (mean +/- SD) underwent endoscopic
      correction of complex VUR. A total of 38 renal refluxing units (RRU) was treated
      as 5 had persistent reflux after open surgery, 16 had duplication, 4 had Hutch
      diverticulum, 6 had small poorly functioning kidneys (less than 20% of relative
      renal function) with grade V VUR, 2 had ureterocele after puncture, 3 had
      persistent stump reflux, 1 had prune belly syndrome, and 1 had urogenital sinus.
      VUR was Grade I in 2, Grade II in 9, Grade III in 11, Grade IV in 10, and Grade V
      in 6 RRU, respectively. RESULTS: The reflux was corrected in 34 (89.4%) RRU after
      a single injection, after second injection in 2 (5.3%) RRU. In 2 (5.3%) RRU, VUR
      downgraded to Grade I (1RRU) and Grade II (1RRU) and they were taken off
      antibiotic prophylaxis. VCUG was performed in 11 (73.3%) of 15 children who
      completed 1 year and in 3 (33.3%) of 9 who completed 3 years of follow up as a
      part of the routine protocol. None showed VUR recurrence. US demonstrated normal
      appearance of kidneys in all patients. CONCLUSION: Our data show that Vantris
      injection provides a high level of reflux resolution in complex cases of VUR.

PMID- 24448912
TI  - Surgical management of hepatic arterioportal fistula in a neonate.
AB  - Congenital arterioportal fistulae in the liver are rare malformations which can
      lead to portal hypertension. We report a hepatic arterioportal fistula in a
      neonate who presented with intestinal hypoperfusion. Computerised tomography
      angiography showed a fistulous communication between the left hepatic artery and
      portal vein with hypoperfusion of small and large bowel. A formal left
      hepatectomy was done followed by clinical improvement and reduction in portal
      venous pressures. The case and the literature pertaining to it are discussed. 

PMID- 24448913
TI  - Isolated appendiceal typhlitis masquerading as perforated appendicitis in the
      setting of acute lymphoblastic leukemia.
AB  - Abdominal pain is common during chemotherapy for childhood leukemia. Clinically
      differentiating typhlitis from appendicitis can be difficult. We present an 8
      year-old boy with abdominal pain in the setting of acute lymphoblastic leukemia
      and neutropenia. Following appendectomy for presumed appendicitis, pathology
      revealed appendiceal typhlitis. Diagnostic and treatment considerations are
      discussed. 

PMID- 24448914
TI  - The two classes of primordial follicles in the mouse ovary: their development,
      physiological functions and implications for future research.
AB  - Ovarian follicles are the basic functional units in the mammalian ovary. This
      review summarizes early pioneering studies and focuses on recent progress that
      has shown that there are two distinct classes of primordial follicles in the
      ovary: the first wave of primordial follicles that are activated immediately
      after they are formed and the adult primordial follicles that are activated
      gradually in later life. These two separate classes have been proposed for two
      decades, but sufficient experimental evidence to support this hypothesis has only
      been obtained recently using newly developed follicular tracing techniques in
      genetically modified mouse models. These two follicle populations differ from
      each other primarily in terms of their developmental dynamics and their
      contributions to ovarian physiology. It is apparent now that these two follicle
      populations should be treated separately, and such knowledge will hopefully lead
      to a more in-depth understanding of how distinct types of primordial follicles
      contribute to physiologic and pathologic alterations of the mammalian ovary. 

PMID- 24448915
TI  - Blood and beyond: properties of circulating and tissue-resident human virus
      specific alphabeta CD8(+) T cells.
AB  - CD8(+) alphabeta T-cell responses form an essential line of defence against viral
      infections. An important part of the mechanisms that control the generation and
      maintenance of these responses have been elucidated in experimental mouse models.
      In recent years it has become clear that CD8(+) T-cell responses in humans not
      only show similarities, but also display differences to those occurring in mice.
      Furthermore, while several viral infections occur primarily in specialised organ
      systems, for obvious reasons, most human CD8(+) T-cell investigations were
      performed on cells deriving from the circulation. Indeed, several lines of
      evidence now point to essential functional differences between virus-specific
      CD8(+) memory T cells found in the circulation and those providing protection in
      organ systems, such as the lungs. In this review, we will focus on summarising
      recent insights into human CD8(+) T-cell differentiation in response to several
      viruses and emphasise that for a complete understanding of anti-viral immunity,
      it is pivotal to scrutinize such responses in both blood and tissue.

PMID- 24448916
TI  - Isolation of specific small-diameter single-wall carbon nanotube species via
      aqueous two-phase extraction.
AB  - Aqueous two-phase extraction is demonstrated to enable isolation of single
      semiconducting and metallic single-wall carbon nanotube species from a synthetic
      mixture. The separation is rapid and robust, with remarkable tunability via
      modification of the surfactant environment set for the separation. 

PMID- 24448917
TI  - 90Y glass microspheres for the treatment of unresectable metastatic liver disease
      from chemotherapy-refractory gastrointestinal cancers: a pilot study.
AB  - PURPOSE: This prospective pilot single-institution study was undertaken to
      document the feasibility, safety, and efficacy of treatment of liver-dominant
      metastatic gastrointestinal cancer using (90)Y glass microspheres. METHODS:
      Between June 2010 and November 2012, 30 adult patients (22 men, eight women;
      median age 61 years) with metastatic chemotherapy-refractory unresectable
      colorectal (n = 15), neuroendocrine (n = 9), intrahepatic cholangiocarcinoma (n =
      3), pancreas (n = 2), and esophageal (n = 1) carcinomas underwent 45 lobar or
      segmental administrations of (90)Y glass microspheres. Data regarding clinical
      and laboratory adverse events (AE) were collected prospectively for 6 months
      after each treatment. Radiographic responses were evaluated using Response
      Evaluation Criteria in Solid Tumors, version 1.1. Time to maximum response,
      response duration, progression-free survival (hepatic and extrahepatic), and
      overall survival were measured. RESULTS: Median target dose and activity were
      111.6 Gy and 2.5 GBq per treatment session, respectively. All but three clinical
      AE were grade 1 or 2 in severity. Serious AE included an unplanned hospital
      admission for carcinoid crisis, grade 3 vomiting, and grade 4 gastric ulcer.
      Patients with colorectal cancer had hepatic objective response rate (ORR) of 27 %
      and a disease control rate (DCR) of 73 %. Median progression-free and overall
      survival were 1.0 and 4.9 months, respectively. Patients with neuroendocrine
      tumors had hepatic ORR and DCR of 78 % and 100 %, respectively. Median
      progression-free survival was 18.5 months for this cohort. CONCLUSIONS: Y glass
      microspheres device has a favorable safety profile and achieved prolonged disease
      control of hepatic tumor burden in a subset of patients, including all patients
      enrolled in the neuroendocrine cohort.

PMID- 24448918
TI  - Automated 3D iotanterstitial lung disease epsilonxtent quantification:
      performance evaluation and correlation to PFTs.
AB  - In this study, the performance of a recently proposed computer-aided diagnosis
      (CAD) scheme in detection and 3D quantification of reticular and ground glass
      pattern extent in chest computed tomography of interstitial lung disease (ILD)
      patients is evaluated. CAD scheme performance was evaluated on a dataset of 37
      volumetric chest scans, considering five representative axial anatomical levels
      per scan. CAD scheme reliability analysis was performed by estimating agreement
      (intraclass correlation coefficient, ICC) of automatically derived ILD pattern
      extent to semi-quantitative disease extent assessment in terms of 29-point rating
      scale provided by two expert radiologists. Receiver operating characteristic
      (ROC) analysis was employed to assess CAD scheme accuracy in ILD pattern
      detection in terms of area under ROC curve (A z ). Correlation of reticular and
      ground glass volumetric pattern extent to pulmonary function tests (PFTs) was
      also investigated. CAD scheme reliability was substantial for ILD extent (ICC =
      0.809) and distinct reticular pattern extent (0.806) and moderate for distinct
      ground glass pattern extent (0.543), performing within inter-observer agreement.
      CAD scheme demonstrated high accuracy in detecting total ILD (A z  = 0.950 +/-
      0.018), while accuracy in detecting distinct reticular and ground glass patterns
      was 0.920 +/- 0.023 and 0.883 +/- 0.024, respectively. Moderate and statistically
      significant negative correlation was found between reticular volumetric pattern
      extent and diffusing capacity, forced expiratory volume in 1 s, forced vital
      capacity, and total lung capacity (R = -0.581, -0.513, -0.494, and -0.446,
      respectively), similar to correlations found between radiologists' semi
      quantitative ratings with PFTs. CAD-based quantification of disease extent is in
      agreement with radiologists' semi-quantitative assessment and correlates to
      specific PFTs, suggesting a potential imaging biomarker for ILD staging and
      management. 

PMID- 24448919
TI  - Towards a theory of PACS deployment: an integrative PACS maturity framework.
AB  - Owing to large financial investments that go along with the picture archiving and
      communication system (PACS) deployments and inconsistent PACS performance
      evaluations, there is a pressing need for a better understanding of the
      implications of PACS deployment in hospitals. We claim that there is a gap in the
      research field, both theoretically and empirically, to explain the success of the
      PACS deployment and maturity in hospitals. Theoretical principles are relevant to
      the PACS performance; maturity and alignment are reviewed from a system and
      complexity perspective. A conceptual model to explain the PACS performance and a
      set of testable hypotheses are then developed. Then, structural equation modeling
      (SEM), i.e. causal modeling, is applied to validate the model and hypotheses
      based on a research sample of 64 hospitals that use PACS, i.e. 70 % of all
      hospitals in the Netherlands. Outcomes of the SEM analyses substantiate that the
      measurements of all constructs are reliable and valid. The PACS alignment-modeled
      as a higher-order construct of five complementary organizational dimensions and
      maturity levels-has a significant positive impact on the PACS performance. This
      result is robust and stable for various sub-samples and segments. This paper
      presents a conceptual model that explains how alignment in deploying PACS in
      hospitals is positively related to the perceived performance of PACS. The
      conceptual model is extended with tools as checklists to systematically identify
      the improvement areas for hospitals in the PACS domain. The holistic approach
      towards PACS alignment and maturity provides a framework for clinical practice. 

PMID- 24448920
TI  - Response to letter to editor: Capturing disutility from waiting time.

PMID- 24448921
TI  - Capturing disutility from waiting time.

PMID- 24448924
TI  - Indirect miniscrew anchorage: biomechanical loading of the dental anchorage
      during mandibular molar protraction-an FEM analysis.
AB  - AIMS: While there are many studies in the literature addressing direct miniscrew
      anchorage, the biomechanical effects of indirect miniscrew anchorage remain
      unknown. The aim of the present study was to biomechanically analyze the load on
      the anchor teeth during mandibular molar protraction using different types of
      anchorage. MATERIALS AND METHODS: Four finite element method (FEM) models of the
      right mandible were created using the morphological CT data of a 21-year-old
      male. All models were morphologically identical, but they differed in anchorage
      type (dental anchorage, direct miniscrew anchorage, indirect miniscrew anchorage
      with one anchor tooth, indirect miniscrew anchorage with two anchor teeth). To
      analyze the load on the dental anchorage during mandibular molar protraction, we
      measured the induced effective strain (ustrain) at specific control points on the
      alveolar bone. RESULTS: With indirect miniscrew anchorage, we observed that the
      effective strain at an average of 7.21 MUstrain (one anchor tooth) or 6.57
      MUstrain (two anchor teeth) was almost as high as in pure dental anchorage where
      no miniscrew was used (mean 8.38 ustrain). In contrast, we noted significantly
      lower strain values in conjunction with direct miniscrew anchorage. We observed
      highly significant differences between direct and indirect simulated miniscrew
      anchorage (p=0.008). CONCLUSION: Our FEM results reveal relatively high loads on
      the dental anchorage when using indirect miniscrew anchorage. This may carry an
      increased risk of anchorage loss during mandibular molar protraction; however,
      further studies are necessary to confirm this.

PMID- 24448925
TI  - Acoustic focusing with engineered node locations for high-performance
      microfluidic particle separation.
AB  - Acoustofluidic devices for manipulating microparticles in fluids are appealing
      for biological sample processing due to their gentle and high-speed capability of
      sorting cell-scale objects. Such devices are generally limited to moving
      particles toward locations at integer fractions of the fluid channel width (1/2,
      1/4, 1/6, etc.). In this work, we introduce a unique approach to acoustophoretic
      device design that overcomes this constraint, allowing us to design the particle
      focusing location anywhere within the microchannel. This is achieved by
      fabricating a second fluid channel in parallel with the sample channel, separated
      from it by a thin silicon wall. The fluids in both channels participate to create
      the ultrasound resonance, while only one channel processes the sample, thus de
      coupling the fluidic and acoustic boundaries. The wall placement and the relative
      widths of the adjacent channels define the particle focusing location. We
      investigate the operating characteristics of a range of these devices to
      determine the configurations that enable effective particle focusing and
      separation. The results show that a sufficiently thin wall negligibly affects
      focusing efficiency and location compared to a single channel without a wall,
      validating the success of this design approach without compromising separation
      performance. Using these principles to design and fabricate an optimized device
      configuration, we demonstrate high-efficiency focusing of microspheres, as well
      as separation of cell-free viruses from mammalian cells. These "transparent wall"
      acoustic devices are capable of over 90% extraction efficiency with 10 MUm
      microspheres at 450 MUL min(-1), and of separating cells (98% purity), from viral
      particles (70% purity) at 100 MUL min(-1). 

PMID- 24448927
TI  - [A social epidemiology for Latin America: the need to go beyond just thinking
      about health inequities].

PMID- 24448928
TI  - [The Revista Peruana de Medicina Experimental y Salud Publica at the end of 2013
      and its perspectives for the coming year].

PMID- 24448926
TI  - Concise review: Stem cell therapies for amyotrophic lateral sclerosis: recent
      advances and prospects for the future.
AB  - Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of
      motor neurons. Although the mechanisms responsible for motor neuron degeneration
      in ALS remain elusive, the development of stem cell-based therapies for the
      treatment of ALS has gained widespread support. Here, we review the types of stem
      cells being considered for therapeutic applications in ALS, and emphasize recent
      preclinical advances that provide supportive rationale for clinical translation.
      We also discuss early trials from around the world translating cellular therapies
      to ALS patients, and offer important considerations for future clinical trial
      design. Although clinical translation is still in its infancy, and additional
      insight into the mechanisms underlying therapeutic efficacy and the establishment
      of long-term safety are required, these studies represent an important first step
      toward the development of effective cellular therapies for the treatment of ALS.

PMID- 24448929
TI  - [Regional disparities in infant mortality in Colombia].
AB  - OBJECTIVES: To study the variations in infant mortality rate (IMR) across
      Colombia's 33 administrative departments over the period 2003-2009, examine
      persistency of variations across departments over time, and relate those
      variations to the impact of socio-economic conditions and availability of care on
      IMR. MATERIALS AND METHODS: Using vital statistics and related socio-economic
      data we establish three types of analysis according to: (a) the variation of the
      departmental IMR (2003-2009), (b) the association between the departmental IMR
      and its key determinants over time, and (c) the lines of causality and relative
      impact of different factors, by using structural equations. RESULTS: The 4.7 fold
      ratio between the highest and lowest departmental IMR (2009) may be
      underestimated considering underreporting, especially in low-income departments.
      There is a negative association between the departmental IMR with time and a set
      of highly correlated variables, such as the mother education, income per capita,
      health insurance level and access to services. CONCLUSIONS: The effect of better
      insurance, availability of private beds, and having doctors attending mothers,
      eclipse the impact of better socioeconomic conditions. The range of services does
      not appear to be influenced by a rational policy; resources are not allocated
      according to the need, but with the general development. Private beds are made
      available where there is better health insurance.

PMID- 24448930
TI  - [Association between tuberculosis incidence and the Human Development Index in
      165 countries of the world].
AB  - OBJECTIVES: Assess relationship between the Human Development Index (HDI) and the
      incidence of tuberculosis (TB) in 165 countries in the World in the period 2005
      2011. MATERIALS AND METHODS: An ecological study was done, using HDI data that
      were obtained from the United Nations Development Program (UNDP), and the
      incidence rates from the Stop TB Program of the World Health Organization (WHO).
      The annual variation of the variables was assessed and non-linear regression
      models (Exponential), were done. RESULTS: At the non-linear regression models, it
      was observed that the relationship between epidemiological and HDI was
      significant, those countries with higher rates presented lower values of HDI
      (p<0.01). Additionally the variation in time was significantly associated with
      HDI variation. CONCLUSIONS: This information reflect the significant influence of
      socioeconomical indicators such as the HDI on the TB incidence rates in the
      World, particularly in endemic countries, being an inverse relationship between
      both types of variables; with an increase or improvement in the HDI, the disease
      incidence rate decreased or it is found lower.

PMID- 24448931
TI  - [Economic impact of chronic, acute and global malnutrition in Peru].
AB  - OBJECTIVES: To estimate the economic impact of chronic, acute and global
      malnutrition in Peru. MATERIALS AND METHODS: This study, through an econometric
      model, estimated the economic impact of child malnutrition in two time horizons
      (incidental retrospective and prospective) during 2011, considering malnutrition
      associated costs of health, education and productivity for the Peruvian economy.
      Information collected is a combination of data coming from the Demographic Survey
      of Family Health, the National Survey of Homes, the 2007 Census of Population and
      Housing, and public budget information, as well as estimates of risks a child is
      exposed to due to malnutrition during their first years of life. RESULTS:
      Nationwide it was found that in the perspective retrospective, the cost of child
      malnutrition in 2011 was 10,999 million soles, which was equal to 2.2% of GDP for
      that same year. Prospective costs nationwide, of those who by 2011 were 0 to 59
      months, reached 4,505 million soles and represented 0.9% of GDP in 2011. Most
      cases stem from losses of productivity in both cases. Moreover, malnutrition
      affects much more both the Andes and jungle regions. CONCLUSIONS: The economic
      impact of child malnutrition represents a significant percentage of GDP, reason
      for which it is necessary to continue investing equitably in its prevention
      through participation with proven efficiency.

PMID- 24448932
TI  - [Antibiotic resistance of streptococcus pneumoniae among healthy nasopharyngeal
      carriers in seven regions of Peru].
AB  - OBJECTIVES: To determine the pattern of antibiotic susceptibility of isolated
      Streptococcus pneumoniae strains of healthy nasopharyngeal carriers younger than
      2 years in seven regions of Peru. MATERIALS AND METHODS: Between 2007 and 2009,
      nasopharyngeal swab samples were collected among 2123 healthy children aged 2-24
      months in growth and development medical practices (CRED) and vaccination offices
      of hospitals and health centers in Lima, Piura, Cusco, Abancay, Arequipa,
      Huancayo, and Iquitos. The resistance to ten antibiotics through disk diffusion
      sensitivity testing of isolated pneumococcus strains was determined. RESULTS: 572
      strains were isolated. High rates of resistance to co-trimoxazole (58%),
      penicillin (52.2% non-sensitive); tetracycline (29,1%); azithromycin (28,9%), and
      erythromycin (26,3%). Resistance to chloramphenicol was low (8.8%).
      Multiresistance was found at 29.5%. Resistance to azithromycin and penicillin was
      different in all seven regions (p<0,05), the highest percentage of non-sensitive
      strains being found in Arequipa (63,6%), whereas the lowest percentage was found
      in Cusco (23.4%). CONCLUSIONS: High levels of resistance found to penicillin, co
      trimoxasole and macrolides in isolated pneumococcus strains of healthy carriers
      in all studied regions, and their association to a previous use of antibiotics,
      represent a significant public health problem in our country. This emphasizes the
      need to implement nationwide strategies to reduce the irrational use of
      antibiotics, especially among children. It is necessary to complement data of
      resistance to penicillin with the determination of minimal inhibitory
      concentration to make proper therapeutic recommendations.

PMID- 24448933
TI  - [Overweight, obesity and chronic mal nutrition in 6 to 9 year-old children in
      Peru, 2009-2010].
AB  - OBJECTIVES: To determine the prevalence of overweight, obesity and chronic
      malnutrition in 6- to 9-year-old children in Peru. MATERIALS AND METHODS: A cross
      cutting study based on the 2009-2010 National Household Survey. The size/age
      ratio was analyzed with references of the National Center for Health Statistic
      (NCSH) and the World Health Organization (WHO), considering less than two
      standard deviations for chronic malnutrition (CM); and the Must and WHO reference
      tables to measure the body mass index with 85 to 95 percentile values for
      overweight and above 95 for obesity. RESULTS: With Must as reference, overweight
      was 12.1% and obesity 9.4%, and according to WHO overweight and obesity were 10.2
      and 11.3% respectively. The prevalence of CM according to NCSH and WHO is 15.4
      and 17.8% respectively. The highest prevalence of CM is in the north (25.2%),
      center (22.9%) and south of (19%) the Highland, while obesity is more present in
      the south coast (28%), Metropolitan Lima (22.8%) and the central Coast (22.5%).
      Of all the children with CM, 6.5% has overweight and 1.2% obesity. CONCLUSIONS:
      CM is decreasing because size averages have improved, however obesity has
      doubled. The presence of CM and obesity in children aged 6 to 9 years old in
      different regions of Peru poses a challenge in the planning of food and nutrition
      policies.

PMID- 24448934
TI  - [Evaluation of occupational exposure to cyclophosphamide in nine hospitals of
      Peru].
AB  - OBJECTIVES: Evaluate occupational exposure to cyclophosphamide in nine hospitals
      of Peru. MATERIALS AND METHODS: Cross-cutting observational study conducted in
      2010, for which 24-hour urine samples were obtained from 96 employees of the
      oncologic mixture units and oncology services of nine hospitals in Peru, the
      quantification of cyclophosphamide was done through the GC-MS methodology ( Gas
      Cromathography-Mass Spectroscopy). Additionally, working surfaces were tested by
      obtaining samples with wet wipes for identification of cyclophosphamide. RESULTS:
      Cyclophosphamide was detected in urine samples in 67 employees (average
      concentration of excretion: 74.2 ng/24 h), accounting for 70% of the total
      population to be assessed. Based on the excretion, total exposure among hospitals
      can be classified as high level (>18.9 ng/24 h), moderate level (1,725 - 18.9
      ng/24 h) and low level (<1,725 ng/24 h), with a percent incidence of 31.3; 26.0
      and 42.7% respectively. Additionally, as part of the environmental evaluation,
      concentrations of cyclosphamide were found in 14.72, 14.98 and 5,12 ng/cm2.
      CONCLUSIONS: Contamination through cyclophosphamide in areas where oncological
      preparations are done and the presence of cyclophosphamide in urine samples of
      workers exposed to cytostatics substance were observed.

PMID- 24448935
TI  - [Genotoxic damage among artisanal and small-scale mining workers exposed to
      mercury].
AB  - OBJECTIVES: To determine the genotoxic damage among artisanal and small-scale
      mining workers exposed to mercury. MATERIALS AND METHODS: Observational cross
      sectional study which evaluated mercury-exposed workers (n=83), whose cells were
      collected by mouth swab for further staining, microscopic observance, micronuclei
      count, and other nuclear alterations. 24-hour urine was also collected for the
      determination of inorganic mercury. RESULTS: 68.7% of participants were male, the
      mean age being 43 +/- 12,4 years (range: 16-76). The average time of occupational
      exposure to mercury was 12,1 +/- 6,7 years, and the contact with mercury was 4,1
      +/- 3,6 kg per person per day. 93% of participants failed to wear personal
      protection gear while handling mercury. Results of biological monitoring showed
      that 17% of participants had concentrations of mercury in urine higher than 2,5
      ug/L, this value being the detection limit of the measurement technique used.
      Results of the genotoxic evaluation evidenced that 15% of people with labor
      exposure to mercury presented micronuclei in mouth epithelial cells, and other
      indicators of nuclear alteration such as nucleoplasmic bridges, gemmation and
      binucleation were found, which are also considered genotoxic events associated to
      the exposure of physical or chemical risk agents. CONCLUSIONS: The finding of
      micronuclei in mouth epithelial cells reflects genotoxic damage associated to the
      labor exposure of mercury used in artisanal and small-scale mining activities.

PMID- 24448936
TI  - [Efficacy of a single dose of Albendazole for soil-transmitted helminth
      infections in school children of a village in Iquitos, Peru].
AB  - OBJECTIVES: To determine the efficacy of single-dose albendazole (400 mg) for
      soil-transmitted helminth infections (STH) in schoolchildren living in one
      community of the city of Iquitos, Peru. MATERIALS AND METHODS: Within the context
      of a randomized controlled trial performed in a peri-urban community of limited
      resources located in Iquitos in the Peruvian Amazon, stool specimens were
      collected from Grade 5 schoolchildren in 18 schools and analysed for STH
      prevalence and intensity. A total of 1,193 school-age children were then dewormed
      with single-dose albendazole (400 mg). Of the 909 children who were found
      positive with at least one STH infection, a random sample of 385 was followed two
      weeks later when a second stool specimen was collected and analyzed. RESULTS: The
      efficacy of albendazole was satisfactory: for Ascaris lumbricoides , with an egg
      reduction rate (ERR) of 99.8%; (95% CI: 99.3-100); for hookworm, with an ERR of
      93.6 %; (95% CI: 88.2-96.6) and, for Trichuris trichiura, with an ERR of 72.7 %;
      (95% CI: 58.5-79.1). CONCLUSIONS: These results are consistent with previous data
      published on the efficacy of albendazole and the directives of the World Health
      Organization. Future research should focus on improving the efficacy of the
      treatment strategies for Trichuris trichiura infection.

PMID- 24448937
TI  - [Gastroprotective and antisecretory effect of a phytochemical made from matico
      leaves (Piper aduncum)].
AB  - OBJECTIVES: To determine the gastroprotective and antisecretory effect of ethanol
      extract from matico leaves (Piper aduncum) in animal models. MATERIALS AND
      METHODS: To evaluate the gastroprotective effect, 220 mice of the Balb C57 strain
      were used. They were randomized in 22 groups of ten animals each, in which the
      formation of gastric ulcers was induced with indomethacin. Gastroprotection was
      determined by evaluating three aspects: inflammation, number of hemorrhagic
      shocks and number of ulcers. To evaluate the antisecretory effect, 64 white male
      Holtzman rats were used, which were randomized in eight groups of eight animals,
      one control and seven groups of treatment with one extract dose level and two
      phytochemical dose levels. Antisecretion was obtained through the pylorus
      ligation. RESULTS: Regarding gastroprotection, dichloromethane, chloroform,
      hexane and methanol extracts decreased inflammation to over 66% (p<0,05). The
      ethanolic extract shows 100% activity in reducing the number of hemorrhagic bands
      (p<0,05). The chloroform extract shows antiulcer activity at 75% (p<0,05). In
      terms of antisecretion, the phytochemical in capsules containing the ethanolic
      extract achieved 72% reduction of the gastric secretion volume (p<0,01) and
      104,3% (p<0,01) PH increase. CONCLUSIONS: In experimental conditions, ethanolic
      extracts, their fractions and phytochemicals have a gastroprotective effect in
      mice and antisecretory effect in rats.

PMID- 24448938
TI  - [Nosocomial infections associated to invasive devices in the intensive care units
      of a national hospital of Lima, Peru].
AB  - In order to describe the incidence of nosocomial infections associated to
      invasive devices in intensive care units (UCI) of the National Hospital Cayetano
      Heredia, a retrospective observational study was conducted using the data from
      the Office of Epidemiology and Environmental Health from 2010 to 2012. A total
      number of 222 nosocomial infections were reported; the general medicine UCI
      reported the highest incidence of pneumonia cases associated to a mechanical
      ventilator in 1000 days of use of the device (28.6); infection of the blood
      stream associated to central venous catheter (11.9), and infection of the urinary
      tract associated to a catheter (8,1). The main infectious agents isolated were
      Pseudomona sp. (32.3%) in the emergency UCI, negative Staphylococcus coagulasa
      (36%) in the general medicine UCI and Candida sp (69.2%) in the Surgery UCI. The
      rates of infections associated to invasive devices were high as in other national
      hospitals with limited resources and infrastructure. 

PMID- 24448939
TI  - [Laboratory performance of primary care units in tuberculosis diagnosis in
      Pelotas, Brazil].
AB  - In order to assess laboratory performance of Primary Care Units (UAP, Spanish
      acronym) in TB diagnosis though the sputum smear test in Pelotas, Brazil, a
      descriptive study was completed which included all sputum smear tests requested
      at eleven primary care units from 2007 to 2010. To assess laboratory performance,
      the number of sputum smear tests requested was quantified as well as the time
      between the request and the reading of the glass slides at the lab. 477 requests
      were registered at UAP. Of this total, only 51,8% were found in the laboratory?s
      record book, the lowest performance was 24,2% and the highest 71,4%. Regarding
      the reading of glass slides, it was determined that 27,7% readings took 8 days or
      more. It is concluded that the primary care units in Pelotas have a low
      laboratory performance in TB diagnosis by sputum smear tests. 

PMID- 24448940
TI  - [Pharmacoepidemiological study of the use of non-steroid antiinflamatory drugs in
      high-risk cardiovascular patients].
AB  - In order to determine the frequency of extended use of non-steroidal anti
      inflammatory drugs (NSAID) in Colombian patients with high cardiovascular risk
      (HCVR), a retrospective study was developed which identified HCVR patients who
      used NSAID for over five continuous months from January 2011 and March 2013.
      Patients chronically receiving nitrates, digitalis and clopidogrel and
      acetylsalicylic acid (ASA), known as HCVR, were identified. An analysis of the
      frequencies of use based on the co-medication received was performed. Concomitant
      use of NSAID was found in 0,35% of consumers of nitrates (average time: 9,5 +/-
      4,4 months), in 0,36% of consumers of clopidogrel and ASA (average time: 9,3 +/-
      3,4 months), and in 0,4% of consumers of digitalis (10,2 +/- 4,6 months). It is
      concluded that there is a low proportion of chronic use of NSAID in high-risk
      cardiovascular patients. 

PMID- 24448942
TI  - [Rehospitalization of elderly patients in a hospital in Lima, Peru].
AB  - In order to determine the frequency and factors associated to rehospitalization
      among elderly patients in a general hospital in Lima (Peru), a longitudinal study
      was conducted. An interview was administered to patients or care providers during
      their hospitalization, and data were collected from their medical records. After
      they were discharged from the hospital, they were followed up for 30 days through
      phone calls to become aware of their condition and if they were hospitalized at
      some health center during this period of time. 276 elderly patients were
      included, 14% of which were rehospitalized. It was found that rehospitalization
      was associated to functional dependency (p=0,003), pneumonia diagnosis upon
      admission (p=0,045) and lack of outpatient control (p<0,001); the latter having
      had RRa 2.22 (95% CI: 1,23-3,22). In conclusion, the most important associated
      factor in the rehospitalization of the elderly is the lack of control visits
      after being discharged. 

PMID- 24448941
TI  - [Traumatic bran injury in children attending a national hospital in Lima, Peru
      2004-2011].
AB  - In order to describe the characteristics of traumatic brain injury (TEC) in
      children seen at the Cayetano Heredia National Hospital from 2004 to 2011, a case
      study was conducted. 316, 14 year-old minors were included, the median age was 4
      +/- 3 years old. 63.9% were male. The main causes of TEC were falls (80.1%) and
      car accidents (10.4%). 42.4% (134/316) occurred in the afternoon. There was a
      higher incidence of falls at home (59.2%). The epidural hematoma (26.9%) was the
      most common intracraneal injury. Intensive care management and neurosurgical
      interventions were required in 15.8 and 14.2% of cases respectively. It is
      concluded that domestic falls were the main cause of accidents for TEC and
      epidural hematoma the most common intracranial injury where children under 5 were
      the most affected. 

PMID- 24448943
TI  - [Inequities in cardiovascular diseases in Latin America].
AB  - In high-income countries, social inequalities in cardiovascular disease (CVD)
      risk are well-documented. Although Latin America has a rich history of theory and
      conceptual discussion regarding social inequalities in health, empirical research
      has been more limited. In this commentary we summarize recent empirical work on
      social inequalities in CVD risk in Latin America, and highlight key research
      needs as well as implications for prevention. Although much remains unknown about
      the social patterning of CVD in Latin America, the limited studies to date
      indicate that inequalities in CVD risk vary across populations and markers of
      socioeconomic position, as well as disease risk marker. The strongest social
      inequalities are seen among women, and in urban areas, with regards to obesity,
      diabetes, and diet. Few studies, though, have been conducted in some parts of
      Latin America, including the countries of Central America and northern South
      America. Vital registration systems and nationally-representative risk factor
      surveys can be important sources of data, as long as information on socioeconomic
      indicators is collected. Longitudinal studies will also be important for
      investigating factors driving social inequalities. As policies and prevention
      strategies are put into place to reduce CVD in Latin America, they must also
      address factors generating social inequalities in CVD risk. 

PMID- 24448944
TI  - [Triple negative breast cancer: a difficult disease to diagnose and treat].
AB  - Triple negative breast cancer (CMTN, Spanish acronym) is a malignant neoplasm
      characterized by the absence of expression of estrogen, progesterone and HER2
      receptors. Recent studies have shown that CMTN is a heterogeneous group including
      different neoplasm with different prognosis. However, because genetic profiles
      are not a standard practice in conventional diagnosis of breast cancer, it is
      hard to properly identify this breast cancer subtype. CMTN is characterized by
      its high-incidence epidemiological patterns in African-American and Latin people,
      and lower incidence in Caucasian people, and constitutes a public health issue
      due to its high morbidity and mortality. Due to the absence of therapeutic
      targets, chemotherapy has a key role in treatment, and many efforts are being
      deployed to seek other combinations of chemotherapy and new drugs, while the
      current guides do not specify treatment for this type of cancer. This document
      reviews the epidemiological and clinical characteristics, the potential prognosis
      factors and some therapeutic strategies against CMTN. 

PMID- 24448945
TI  - [Economic growth and health inequities].
AB  - This essay reviews the relation between health inequities and economic growth.
      The general meaning of these and ancillary concepts (economic development, health
      inequalities) is briefly reviewed. Some studies illustrating different hypotheses
      on the long-run historical evolution of health inequalities are presented, and
      three case studies -the United States in 1920-1940 and in recent years, Finland
      during the expansion of the 1980s and the recession of the 1990s- are reviewed to
      demonstrate the evolution of health inequalities during the periods of expansion
      and recession in markets economies that conform to the so-called business cycle.
      Health inequities between ethnic groups and social classes are often found in
      modern societies, and some of these disparities seem to be widening. Periods of
      economic expansion do not seem favorable for the lessening of health
      inequalities. Contrarily, and counter-intuitively, evidence rather suggests that
      it is during periods of recession that gaps in health between privileged and
      disadvantaged groups tend to narrow. 

PMID- 24448946
TI  - [Health equity in the world's most unequal region: a challenge for public policy
      in Latin America].
AB  - Re-democratization has transformed the social agenda and the role of the state in
      Latin America with a growing commitment to health equity and social justice, yet
      these aspirations are strained by the region's profound socioeconomic
      inequalities. Efforts to provide universal coverage to the right to health have
      led to the development of a variety of public policies, whose scope depends on
      how the concepts of health and equity are understood. In general, policy action
      has centered on health system reforms and only recently on integrated
      intersectorial action to address wider social determinants of health,
      particularly structural determinants. Furthermore, if the goal is health equity
      the predominant minimum standards approach cannot be the final answer, but only a
      step on the road to equality. Finally, realizing universal coverage of the right
      to health through public policy requires the strengthening of governmental
      institutional capacities with an intersectorial and participatory lens. 

PMID- 24448947
TI  - [Inequity and health in the workplace: exploring an emergent area].
AB  - Work, under fair employment and decent work, reduces inequities in health.
      Nowadays it seems, however, that obtaining and carrying out a job and worker
      performance take precedence over the aforementioned attributes. Workers are not
      only exposed to accidents, diseases caused by various agents, ergonomic and
      psychosocial risks but also affected by work modes imposed by the "wildmarket",
      such as the lack of social security benefits. Member countries of the
      International Labour Organization (ILO) should institute occupational health and
      safety policies in order to reduce the above mentioned inequities. Nonetheless,
      governments, which would guarantee such policies, seem to have become
      intermediaries in favor of large corporations. It is essential to define and
      strengthen actions that create jobs in decent and appropriate conditions with a
      view to generating equity, equality, and social well-being.

PMID- 24448948
TI  - [Inequity in health affects the development in Peru].
AB  - Unfair and avoidable differences in exercising the right to health coexist with
      the Universal Declaration of Human Rights since 1948. Some causes of the
      persistent inequality inferred after Alma-Ata are insufficient funding,
      development of national health systems without adequate prioritization, and since
      the 80s with economic consensus to introduce the health market model. Health in
      Peru is still an area of little progress, ostensible inequality and limited
      participation in development. Policies in the 20th century are still
      insufficient; and missing opportunities like increasing the value of exports over
      a decade ago is a recurring issue. For a health reform to be successful in terms
      of equality and development, it is necessary to agree on a state policy,
      establish a modern and equitable social security funding system and eradicate the
      inconsistencies in the national health system.

PMID- 24448949
TI  - [Inequities in health: the case of dengue].
AB  - Impoverished populations carry a disproportionately high share of the burden of
      neglected tropical diseases, including dengue. The burden of dengue is high among
      poor people because they often live in communities where mosquito vectors are
      abundant, because they use less vector-human barrier methods, and because
      interventions tend to be less effective in disadvantaged populations. We believe
      that a better understanding and management of the "causes behind the causes" of
      dengue would lead to more equitable and more effective control strategies. Two
      main ideas are worked out. First, we propose targeted interventions in well
      defined geographical areas with high risk of dengue transmission. The definition
      of these high-risk areas should be based on socio-economical, entomological,
      environmental as well as epidemiological information. Second, there is a need to
      adapt dengue control tools to local, context-specific factors, in active
      collaboration with the sectors involved in risk management as well as with the
      affected communities.

PMID- 24448950
TI  - [Interaction, synergy and antagonism in prospective epidemiological studies].
AB  - In public health there is a growing appreciation for the advantage of the
      additive scale to better understand the impacts of factors involved in a health
      event. It is necessary to always remember that the concept of statistical
      interaction is scale dependent. In the causal relationship between a response and
      the presence of two or more factors, the concepts interaction, synergy and
      antagonism are the key ideas. The aim of this note is to show an application of
      the concepts interaction, synergy and antagonism in prospective studies from a
      public health perspective. We present three scenarios that illustrate analyses of
      interaction, independence, synergy and antagonism. Stata 12 software was used for
      fitting models (log-binomial model and Poisson) and estimating parameters.
      Appendixes are provided with concepts and Stata commands used in the processes of
      simulation and parameter estimation. 

PMID- 24448951
TI  - [Looking for a more participative healthcare: sharing medical decision making].
AB  - The healthcare model is shifting from a paternalistic towards a more inclusive
      and participative approach, such as shared decision making (SDM). SDM considers
      patients as autonomous and responsible agents. SDM is a therapeutic approach
      where healthcare providers and patients share the best evidence available to make
      a decision according to the values and preferences of the patient. Decision aids
      are tools that can facilitate this information exchange. These tools help
      patients to increase knowledge about options, reduce decisional conflict and
      improve satisfaction. Additionally, communication skills play a key role within
      the professional-patient relationship, as they facilitate sharing information and
      preferences in an effective and respectful manner. This therapeutic approach
      could support the reduction of health inequalities that affect Latin America, as
      it promotes an active and informed participation of patients in their healthcare
      process. 

PMID- 24448952
TI  - [Sexual diversity, health and citizenship].
AB  - Non-heterosexual sexual orientations are no longer considered pathological by the
      American Psychiatric Association since 1973 and the World Health Organization
      since 1990. However, to many authors, these changes in Latin America have not
      been translated into an inclusive healthcare provision or the recognition of non
      heterosexual citizens with full rights. The purpose of this document is to
      provide a theoretical view regarding sexuality, proposing proper conditions that
      allow to successfully facing arising challenges. Thus, the regulating role of
      medicine over sexuality has been exposed, which has led to both academic and
      political reactions. The progressive change given in medical science has been
      pointed out: from considering non-heterosexual sexuality to be pathological to
      offering, in theory at least, inclusion. The negative impacts of what an adverse
      social environment causes to an individual are described. Finally, specific
      actions are proposed to provide better health services to non-heterosexual
      citizens. 

PMID- 24448953
TI  - [Chorea and high altitude erythrocytosis: a case report].
AB  - Chorea is a movement disorder which is rarely caused by erythrocytosis.
      Erithrocytosis or polycythemia is the augmentation of the absolute erythrocytic
      mass and its most common primary cause is polycythemia vera. Some of the
      secondary causes are erythrocytosis by central hipoxia occurring in people who
      live in the highlands. Chore is a rare neurological manifestation of
      erythrocytosis occurring in 0.5 to 2% of these patients. There was a report of a
      71 year-old male patient with generalized chorea of sudden onset predominant in
      mouth, tongue and face and lower limbs, secondary to acquired erythrocytosis,
      which improved after the number of erythrocytes decreased through successive
      sessions of phlebotomy. 

PMID- 24448954
TI  - [Inequity in health: its historical development].
AB  - Health inequity, main issue of contemporary debates on public health, is based on
      philosophical and historical concepts that date back to the idea of justice from
      classic Greece. The Aristotelian approach on distributive justice and its higher
      form, epiekeia or equity, has been reviewed, as well as how this evolves from the
      Middle Ages and modernity to the heart of the debate of a variety of thinkers
      such as liberal Rawls and Nobel laureate Amartya Sen. On this conceptual debate
      lies the World Health Organization version that links equity to health
      determinants and intends to make it operational through the equitable provision
      of health services.

PMID- 24448955
TI  - [Deficiencies in prescription and access to diet-based treatment of chronic
      kidney disease in hemodialysis: a glimpse into the context of inequity].

PMID- 24448956
TI  - [Insufficient cardiovascular surgeries in children with congenital heart defects
      in Arequipa, Peru].

PMID- 24448957
TI  - [Need to detect a mechanism of resistance to macrolides, lincosamides and
      streptogramins in Streptococcus pyogenes and Staphylococcus aureus in complicated
      small pox].

PMID- 24448958
TI  - [Registration the quality of medical records in a health center Callao, Peru
      2013].

PMID- 24448959
TI  - [Scientific production of life members of the Peruvian National Academy of
      Medical Researchers].

PMID- 24448960
TI  - [Dose-effect curve of anthocyanins of three extracts of Zea mays L. (purple corn)
      in the vasodilation of rat aortic rings].

PMID- 24448961
TI  - [Newborn screening in Peru: where are we going?].

PMID- 24448962
TI  - [Comments to the article: evaluation of the impact of powder multimicronutrients
      on child anemia in three Andean regions of Peru].

PMID- 24448963
TI  - [Comments to article: evaluation of the impact of powder multimicronutrients on
      child anemia in three Andean regions of Peru - authors reply].

PMID- 24448965
TI  - A synthetic tryptophan metabolite reduces hemorrhagic area and inflammation after
      pulmonary radiofrequency ablation in rabbit nonneoplastic lungs.
AB  - PURPOSE: The purpose of this study was to determine the effect of a synthetic
      tryptophan metabolite, tranilast [N-(3,4-dimethoxycinnamoyl)-anthranilic acid],
      on inflammatory and hemorrhagic areas after pulmonary radiofrequency ablation
      (RFA) in rabbits. MATERIALS AND METHODS: Percutaneous RFA using a 17-gauge LeVeen
      electrode was performed in normal rabbit lungs. The rabbits were divided into
      tranilast-treated (300 mg/kg/day, orally) and control groups (n = 24/group). The
      effects of tranilast were evaluated using multidetector-row computed tomography
      (CT), histology, and immunohistochemistry immediately after RFA on days 1, 7, 14,
      and 28. RESULTS: Oral administration of tranilast significantly reduced the size
      of ablated lesions assessed using CT and histology on days 7 and 14. Furthermore,
      it reduced the hemorrhagic areas on day 7 and inflammatory areas on day 14, but
      did not affect the areas of coagulation necrosis on days 1, 7, 14, and 28.
      Immunohistochemical analysis showed an increase in the ratio of CD163-positive
      macrophage areas to rabbit macrophage (RAM11)-positive pan-macrophage areas and a
      decrease in the number of nuclear factor-kappaB-positive nuclei and CD31-positive
      microvessels in the tranilast group on days 7 and/or 14. CONCLUSIONS: The results
      suggest that tranilast modulates the repair process after pulmonary RFA through
      macrophage accumulation, suppression of inflammation, and angiogenesis.

PMID- 24448964
TI  - Extracellular adenosine controls NKT-cell-dependent hepatitis induction.
AB  - Extracellular adenosine regulates inflammatory responses via the A2A adenosine
      receptor (A2AR). A2AR deficiency results in much exaggerated acute hepatitis,
      indicating nonredundancy of adenosine-A2AR pathway in inhibiting immune
      activation. To identify a critical target of immunoregulatory effect of
      extracellular adenosine, we focused on NKT cells, which play an indispensable
      role in hepatitis. An A2AR agonist abolished NKT-cell-dependent induction of
      acute hepatitis by concanavalin A (Con A) or alpha-galactosylceramide in mice,
      corresponding to downregulation of activation markers and cytokines in NKT cells
      and of NK-cell co-activation. These results show that A2AR signaling can
      downregulate NKT-cell activation and suppress NKT-cell-triggered inflammatory
      responses. Next, we hypothesized that NKT cells might be under physiological
      control of the adenosine-A2AR pathway. Indeed, both Con A and alpha
      galactosylceramide induced more severe hepatitis in A2AR-deficient mice than in
      WT controls. Transfer of A2AR-deficient NKT cells into A2AR-expressing recipients
      resulted in exaggeration of Con A-induced liver damage, suggesting that NKT-cell
      activation is controlled by endogenous adenosine via A2AR, and this physiological
      regulatory mechanism of NKT cells is critical in the control of tissue-damaging
      inflammation. The current study suggests the possibility to manipulate NKT-cell
      activity in inflammatory disorders through intervention to the adenosine-A2AR
      pathway. 

PMID- 24448966
TI  - Perceptions among infertile couples of lifestyle behaviors and in vitro
      fertilization (IVF) success.
AB  - PURPOSE: To assess how patients perceive various lifestyle behaviors impact IVF
      success. METHODS: Cross-sectional study of heterosexual, English-speaking couples
      (n = 138) who completed web-based surveys during IVF treatment cycle. Perceived
      impact of lifestyle choices assessed by multivariable logistic regression and p
      value tests for linear trend (Pt). RESULT(S): During the IVF cycle, most patients
      consider it helpful for women to exercise (76 %), avoid stress (87 %) and limit
      activity after embryo transfer (92 %). The majority of patients (62 %) consider
      rigorous exercise (4+ h/week) helpful and nearly one-third (32 %) perceive
      benefit to complete bed rest after transfer. Overall, couples with a sex-specific
      infertility diagnosis are more likely to consider partner's lifestyle choices
      impactful: male-factor couples are more likely to consider it helpful for men to
      limit cellular phone use (OR:2.73,CI:1.06-7.04) and diminished ovarian reserve
      couples are more likely to consider it helpful for women to limit exposure to
      plastics (OR:2.38,CI:1.03-5.51). Patients at higher levels of education (Pt <
      0.01) and income (P(t) < 0.01) are less likely to consider lifestyle impactful.
      CONCLUSION(S): Patient perceptions of the impact of lifestyle factors on IVF
      success vary by sex, infertility diagnosis and socioeconomic factors. Despite
      counseling to the contrary, many patients perceive benefit to rigorous exercise
      during the IVF cycle and complete bedrest following transfer. Results provide
      insight into patient beliefs and highlight opportunities to improve patient
      education, alleviate patient anxieties and potentially improve IVF outcomes.

PMID- 24448967
TI  - Pyoderma gangrenosum following breast reduction: treatment with topical
      tacrolimus and steroids.
AB  - Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory dermatosis
      usually associated with autoimmune disorders. Wounds may mimic a necrotizing
      infection, and the diagnosis is usually made after antibiotic therapy fails.
      Debridement may cause even larger wounds because of pathergy, so PG treatment
      consists of corticosteroids and local wound care. Pyoderma gangrenosum can be a
      devastating complication of breast and aesthetic surgery. We describe a case of
      PG following unilateral breast reduction that resulted in systemic inflammatory
      response; after treatment with prednisone and topical tacrolimus, the PG was
      resolved. The application of topical tacrolimus may reduce the need for prolonged
      corticosteroids. LEVEL OF EVIDENCE: 5.

PMID- 24448968
TI  - Dimethocaine, a synthetic cocaine analogue: studies on its in-vivo metabolism and
      its detectability in urine by means of a rat model and liquid chromatography
      linear ion-trap (high-resolution) mass spectrometry.
AB  - Dimethocaine (DMC, larocaine), a synthetic derivative of cocaine, is a widely
      distributed "legal high" consumed as a "new psychoactive substance" (NPS) without
      any safety testing, for example studies of metabolism. Therefore, the purpose of
      this work was to study its in-vivo and in-vitro metabolism by use of liquid
      chromatography-(high resolution) mass spectrometry (LC-HRMS(n)). DMC was
      administered to male Wistar rats (20 mg kg(-1)) and their urine was extracted
      either by solid-phase extraction after enzymatic cleavage of conjugates or by use
      of protein precipitation (PP). The metabolites were separated and identified by
      LC-HRMS(n). The main phase I reactions were ester hydrolysis, deethylation,
      hydroxylation of the aromatic system, and a combination of these. The main phase
      II reaction was N-acetylation of the p-aminobenzoic acid part of the unchanged
      parent compound and of several phase I metabolites. The metabolites identified
      were then used for identification of DMC in rat urine after application of a
      common user's dose. By use of GC-MS and LC-MS(n) standard urine-screening
      approaches (SUSAs), DMC and its metabolites could be detected in the urine
      samples.

PMID- 24448969
TI  - Development and validation of HTS assay for screening the calcium-activated
      chloride channel modulators in TMEM16A stably expressed CHO cells.
AB  - Calcium-activated chloride channels (CaCCs), for example TMEM16A, are widely
      expressed in a variety of tissues and are involved in many important
      physiological functions. We developed and validated an atomic absorption
      spectroscopy (AAS)-based detection system for high-throughput screening (HTS) of
      CaCC modulators. With this assay, Cl(-) flux from CHO cells stably transfected
      with TMEM16A is assayed indirectly, by measuring excess silver ions (Ag(+)) in
      the supernatant of AgCl precipitates. The screening process involved four steps:
      (1) TMEM16A CHO cells were incubated in high-K(+) and high-Cl(-) buffer with test
      compounds, and with ionomycin as Ca(2+) ionophore, for 12 min; (2) cells were
      washed with a low-K(+), Cl(-)-free and Ca(2+)-free buffer; (3) CaCC/TMEM16A were
      activated in high-K(+), Cl(-)-free buffer with ionomycin (10 MUmol L(-1)) for 12
      min; and (4) excess Ag(+) concentration was measured using an ion channel reader
      (ICR, an AAS system). The assay can be used to screen CaCC activators and
      inhibitors at the same time. With this assay, positive control drugs, including
      NPPB, CaCCinh-A01, flufenamic acid (Flu) and Eact, all had good concentration
      dependent effects on CaCC/TMEM16A. NPPB and CaCCinh-A01 inhibited the
      CaCC/TMEM16A currents completely at 300 MUmol L(-1), with IC50 values of 39.35 +/
      4.72 MUmol L(-1) and 6.35 +/- 0.27 MUmol L(-1), respectively; and Eact,
      activated CaCC/TMEM16A, with an EC50 value of 3.92 +/- 0.87 MUmol L(-1). 

PMID- 24448970
TI  - Metabolomic study in plasma, liver and kidney of mice exposed to inorganic
      arsenic based on mass spectrometry.
AB  - The mechanism of arsenic toxicity still remains unclear, although enzymatic
      inhibition, impaired antioxidants metabolism and oxidative stress may play a
      role. The toxicological effects of trivalent inorganic arsenic on laboratory
      mouse Mus musculus after oral administration (3 mg/kg body weight/day) were
      investigated along 12 days, using a metabolomic approach based on direct infusion
      mass spectrometry to polar and lipophilic extracts from different organs and
      fluids (liver, kidney, and plasma). Positive and negative acquisition modes
      (ESI(+)/ESI(-)) were used throughout the experiments. The most significant
      endogenous metabolites affected by exposure were traced by partial least square
      discriminant analysis and confirmed by tandem mass spectrometry (MS/MS) and gas
      chromatography coupled to MS. In this work, the toxic effect of arsenic has been
      related with important metabolic pathways, such as energy metabolism (e.g.,
      glycolysis, Krebs cycle), amino acids metabolism, choline metabolism, methionine
      cycle, and degradation of membrane phospholipids (cell apoptosis). In addition,
      this work illustrates the high reliability of mass spectrometry based on a
      metabolomic approach to study the biochemical effects induced by metal exposure.

PMID- 24448971
TI  - FIB-SEM imaging of carbon nanotubes in mouse lung tissue.
AB  - Ultrastructural characterisation is important for understanding carbon nanotube
      (CNT) toxicity and how the CNTs interact with cells and tissues. The standard
      method for this involves using transmission electron microscopy (TEM). However,
      in particular, the sample preparation, using a microtome to cut thin sample
      sections for TEM, can be challenging for investigation of regions with
      agglomerations of large and stiff CNTs because the CNTs cut with difficulty. As a
      consequence, the sectioning diamond knife may be damaged and the uncut CNTs are
      left protruding from the embedded block surface excluding them from TEM analysis.
      To provide an alternative to ultramicrotomy and subsequent TEM imaging, we
      studied focused ion beam scanning electron microscopy (FIB-SEM) of CNTs in the
      lungs of mice, and we evaluated the applicability of the method compared to TEM.
      FIB-SEM can provide serial section volume imaging not easily obtained with TEM,
      but it is time-consuming to locate CNTs in the tissue. We demonstrate that
      protruding CNTs after ultramicrotomy can be used to locate the region of
      interest, and we present FIB-SEM images of CNTs in lung tissue. FIB-SEM imaging
      was applied to lung tissue from mice which had been intratracheally instilled
      with two different multiwalled CNTs; one being short and thin, and the other
      longer and thicker. FIB-SEM was found to be most suitable for detection of the
      large CNTs (O ca. 70 nm), and to be well suited for studying CNT agglomerates in
      biological samples which is challenging using standard TEM techniques. 

PMID- 24448972
TI  - Efficacy and acceptability of acute treatments for persistent depressive
      disorder: a network meta-analysis.
AB  - BACKGROUND: We aimed to synthesize the available evidence on the relative
      efficacy and acceptability of specific treatments for persistent depressive
      disorder. METHODS: We searched several databases up to January 2013 and included
      randomized controlled trials that compared acute pharmacological,
      psychotherapeutic, and combined interventions with each other or placebo. The
      outcome measures were the proportion of patients who responded to (efficacy) or
      dropped out from (acceptability) the allocated treatment. Data synthesis was
      performed with network meta-analysis. RESULTS: A network of 45 trials that tested
      28 drugs included data from 5,806 and 5,348 patients concerning efficacy and
      acceptability, respectively. A second network of 15 trials that tested five
      psychotherapeutic and five combined interventions included data from 2,657 and
      2,719 patients concerning efficacy and acceptability, respectively. Among
      sufficiently tested treatments, fluoxetine (odds ratio (OR) 2.94), paroxetine
      (3.79), sertraline (4.47), moclobemide (6.98), imipramine (4.53), ritanserin
      (2.35), amisulpride (5.63), and acetyl-l-carnitine (5.67) were significantly more
      effective than placebo. Pairwise comparisons showed advantages of moclobemide
      (2.38) and amisulpride (1.92) over fluoxetine. Sertraline (0.57) and amisulpride
      (0.53) showed a lower dropout rate than imipramine. Interpersonal psychotherapy
      with medication outperformed medication alone in chronic major depression but not
      in dysthymia. Evidence on cognitive behavioral analysis system of psychotherapy
      plus medication was partly inconclusive. Interpersonal psychotherapy was less
      effective than medication (0.48) and cognitive behavioral analysis system of
      psychotherapy (0.45). Several other treatments were tested in single studies.
      CONCLUSIONS: Several evidence-based acute pharmacological, psychotherapeutic, and
      combined treatments for persistent depressive disorder are available with
      significant differences between them.

PMID- 24448974
TI  - Intake of vegetables and fruit and risk of esophageal adenocarcinoma: a meta
      analysis of observational studies.
AB  - OBJECTIVES: To study the association between the intake of fruit and vegetables
      and risk of esophageal adenocarcinoma (EAC), we summarized the evidence from
      observational studies in categorical and linear dose-response meta-analyses.
      METHODS: Eligible studies published up to June 2013 were retrieved via
      computerized searches of MEDLINE and EMBASE. Random-effects models were used to
      calculate summary relative risks (SRRs) and the corresponding 95% confidence
      intervals (CIs). Between-study heterogeneity was assessed using the Cochran's Q
      and I (2) statistics. RESULTS: A total of 12 studies involving 1,572 cases of EAC
      were included in this meta-analysis. Based on the highest versus lowest analysis,
      inverse associations were observed between intakes of vegetable (SRRs = 0.76, 95%
      CIs 0.59-0.96; P heterogeneity = 0.098, I (2) 40.4%; n = 9 studies), intakes of
      fruit (SRRs = 0.73, 95% CIs, 0.55-0.98; P heterogeneity = 0.03, I (2) = 52.9%; n
      = 9 studies), and intakes of total vegetables and fruit combined (SRRs = 0.68,
      95% CI 0.49-0.93; P heterogeneity = 0.162, I (2) = 38.9%; n = 5 studies). Similar
      results were also observed in a linear dose-response analysis. CONCLUSION: These
      data support the hypothesis that intakes of vegetables and fruit may
      significantly reduce the risk of EAC. Further investigation with prospective
      designs, validated questionnaires, and good control of important confounders is
      warranted.

PMID- 24448973
TI  - Xpert(r) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in
      adults.
AB  - BACKGROUND: Accurate, rapid detection of tuberculosis (TB) and TB drug resistance
      is critical for improving patient care and decreasing TB transmission. Xpert(r)
      MTB/RIF assay is an automated test that can detect both TB and rifampicin
      resistance, generally within two hours after starting the test, with minimal
      hands-on technical time. The World Health Organization (WHO) issued initial
      recommendations on Xpert(r) MTB/RIF in early 2011. A Cochrane Review on the
      diagnostic accuracy of Xpert(r) MTB/RIF for pulmonary TB and rifampicin
      resistance was published January 2013. We performed this updated Cochrane Review
      as part of a WHO process to develop updated guidelines on the use of the test.
      OBJECTIVES: To assess the diagnostic accuracy of Xpert(r) MTB/RIF for pulmonary
      TB (TB detection), where Xpert(r) MTB/RIF was used as both an initial test
      replacing microscopy and an add-on test following a negative smear microscopy
      result.To assess the diagnostic accuracy of Xpert(r) MTB/RIF for rifampicin
      resistance detection, where Xpert(r) MTB/RIF was used as the initial test
      replacing culture-based drug susceptibility testing (DST).The populations of
      interest were adults presumed to have pulmonary, rifampicin-resistant or
      multidrug-resistant TB (MDR-TB), with or without HIV infection. The settings of
      interest were intermediate- and peripheral-level laboratories. The latter may be
      associated with primary health care facilities. SEARCH METHODS: We searched for
      publications in any language up to 7 February 2013 in the following databases:
      Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web
      of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the
      metaRegister of Controlled Trials (mRCT) and the search portal of the WHO
      International Clinical Trials Registry Platform to identify ongoing trials.
      SELECTION CRITERIA: We included randomized controlled trials, cross-sectional
      studies, and cohort studies using respiratory specimens that allowed for
      extraction of data evaluating Xpert(r) MTB/RIF against the reference standard. We
      excluded gastric fluid specimens. The reference standard for TB was culture and
      for rifampicin resistance was phenotypic culture-based DST. DATA COLLECTION AND
      ANALYSIS: For each study, two review authors independently extracted data using a
      standardized form. When possible, we extracted data for subgroups by smear and
      HIV status. We assessed the quality of studies using QUADAS-2 and carried out
      meta-analyses to estimate pooled sensitivity and specificity of Xpert(r) MTB/RIF
      separately for TB detection and rifampicin resistance detection. For TB
      detection, we performed the majority of analyses using a bivariate random-effects
      model and compared the sensitivity of Xpert(r) MTB/RIF and smear microscopy
      against culture as reference standard. For rifampicin resistance detection, we
      undertook univariate meta-analyses for sensitivity and specificity separately to
      include studies in which no rifampicin resistance was detected. MAIN RESULTS: We
      included 27 unique studies (integrating nine new studies) involving 9557
      participants. Sixteen studies (59%) were performed in low- or middle-income
      countries. For all QUADAS-2 domains, most studies were at low risk of bias and
      low concern regarding applicability.As an initial test replacing smear
      microscopy, Xpert(r) MTB/RIF pooled sensitivity was 89% [95% Credible Interval
      (CrI) 85% to 92%] and pooled specificity 99% (95% CrI 98% to 99%), (22 studies,
      8998 participants: 2953 confirmed TB, 6045 non-TB).As an add-on test following a
      negative smear microscopy result, Xpert(r)MTB/RIF pooled sensitivity was 67% (95%
      CrI 60% to 74%) and pooled specificity 99% (95% CrI 98% to 99%; 21 studies, 6950
      participants).For smear-positive, culture-positive TB, Xpert(r) MTB/RIF pooled
      sensitivity was 98% (95% CrI 97% to 99%; 21 studies, 1936 participants).For
      people with HIV infection, Xpert(r) MTB/RIF pooled sensitivity was 79% (95% CrI
      70% to 86%; 7 studies, 1789 participants), and for people without HIV infection,
      it was 86% (95% CrI 76% to 92%; 7 studies, 1470 participants). Comparison with
      smear microscopy In comparison with smear microscopy, Xpert(r) MTB/RIF increased
      TB detection among culture-confirmed cases by 23% (95% CrI 15% to 32%; 21
      studies, 8880 participants).For TB detection, if pooled sensitivity estimates for
      Xpert(r) MTB/RIF and smear microscopy are applied to a hypothetical cohort of
      1000 patients where 10% of those with symptoms have TB, Xpert(r) MTB/RIF will
      diagnose 88 cases and miss 12 cases, whereas sputum microscopy will diagnose 65
      cases and miss 35 cases. Rifampicin resistance For rifampicin resistance
      detection, Xpert(r) MTB/RIF pooled sensitivity was 95% (95% CrI 90% to 97%; 17
      studies, 555 rifampicin resistance positives) and pooled specificity was 98% (95%
      CrI 97% to 99%; 24 studies, 2411 rifampicin resistance negatives). Among 180
      specimens with nontuberculous mycobacteria (NTM), Xpert(r) MTB/RIF was positive
      in only one specimen that grew NTM (14 studies, 2626 participants).For rifampicin
      resistance detection, if the pooled accuracy estimates for Xpert(r) MTB/RIF are
      applied to a hypothetical cohort of 1000 individuals where 15% of those with
      symptoms are rifampicin resistant, Xpert(r) MTB/RIF would correctly identify 143
      individuals as rifampicin resistant and miss eight cases, and correctly identify
      833 individuals as rifampicin susceptible and misclassify 17 individuals as
      resistant. Where 5% of those with symptoms are rifampicin resistant, Xpert(r)
      MTB/RIF would correctly identify 48 individuals as rifampicin resistant and miss
      three cases and correctly identify 931 individuals as rifampicin susceptible and
      misclassify 19 individuals as resistant. AUTHORS' CONCLUSIONS: In adults thought
      to have TB, with or without HIV infection, Xpert(r) MTB/RIF is sensitive and
      specific. Compared with smear microscopy, Xpert(r) MTB/RIF substantially
      increases TB detection among culture-confirmed cases. Xpert(r) MTB/RIF has higher
      sensitivity for TB detection in smear-positive than smear-negative patients.
      Nonetheless, this test may be valuable as an add-on test following smear
      microscopy in patients previously found to be smear-negative. For rifampicin
      resistance detection, Xpert(r) MTB/RIF provides accurate results and can allow
      rapid initiation of MDR-TB treatment, pending results from conventional culture
      and DST. The tests are expensive, so current research evaluating the use of
      Xpert(r) MTB/RIF in TB programmes in high TB burden settings will help evaluate
      how this investment may help start treatment promptly and improve outcomes.

PMID- 24448975
TI  - n-3 LC-PUFA supplementation: effects on infant and maternal outcomes.
AB  - BACKGROUND: Long-chain polyunsaturated fatty acids (LC-PUFA), particularly
      docosahexaenoic acid (DHA) and arachidonic acid, are, respectively, n-3 and n-6
      family members and play an important role in fetal and infant growth and
      development. Pregnancy and lactation impose special nutritional needs for the
      mother-fetus situation. Since the LC-PUFA required by the fetus is supplied by
      preferential placental transfer of preformed LC-PUFA rather than their precursor,
      it has been hypothesized that additional maternal supply of LC-PUFA, especially
      DHA, during pregnancy may improve maternal and infant outcomes. AIM: To summarize
      evidences of the effect of n-3 LC-PUFA intake during pregnancy and lactation on
      maternal and infant outcomes in order to offer a comprehensive view of this issue
      that should be useful for clinical practice. RESULTS: Maternal n-3 LC-PUFA
      supplementation may reduce risk for early preterm birth >34 weeks and seems very
      promising for primary allergy prevention during childhood. On the contrary, there
      are not sufficient data proving that the consumption of oils rich in n-3 LC-PUFA
      during pregnancy optimizes child's visual and neurodevelopment and reduces the
      risk for preeclampsia and perinatal depression; the implications of these
      findings remain to be elucidated. CONCLUSION: The implications of n-3 LC-PUFA
      supplementation on fetal development, maternal outcomes and later infant growth
      is worth being elucidated and is promising in its potential for a positive impact
      on fetal and maternal outcomes.

PMID- 24448976
TI  - Nuclear factor-kappa B ligand and osteoprotegerin levels in serum and gingival
      crevicular fluid in patients with bone metastases treated with zoledronic acid.
AB  - Bone metastases are frequently observed in patients with certain types of cancer
      and are significant cause of morbidity. Zoledronic acid (ZA) is routinely
      prescribed for patients with bone metastases by affecting osteoclast function. We
      aimed to assess the effect of ZA over time in patients with bone metastases by
      analyzing novel bone turnover marker levels including receptor activator of
      nuclear factor-k B ligand (RANKL) and osteoprotegerin (OPG) in serum and gingival
      crevicular fluid (GCF). Also, associations between these bone turnover markers
      with hematological and biochemistry dysregulation were studied. The study
      enrolled patients with bone metastases including 32 patients diagnosed with solid
      tumors and 15 patients with multiple myeloma. In these patients, GCF and serum
      RANKL and OPG levels were measured and compared with measures of hematological
      and biochemical parameters before and after 3 months of ZA therapy. Mean subject
      age was 54 years old with a range of 28-80 years. Skeletal-related events were
      observed in 8.5% of all patients. After the 3-month treatment of ZA therapy, no
      significant differences were found in serum and GCF levels of RANKL and OPG when
      compared with before treatment levels. GCF RANKL levels at baseline and following
      3 months of ZA therapy were significantly higher in patients with solid tumors
      when compared patients diagnosed with multiple myeloma (p=0.001; p<0.001,
      respectively). GCF OPG levels after the entire course of ZA therapy were greater
      in patients with 5 or more bone metastases (p=0.04). For patients with multiple
      myeloma, control GCF OPG was negatively correlated with control platelet and WBC
      counts (p=0.018 and p=0.027, respectively). A negative correlation was observed
      between control serum RANKL and control serum OPG levels in myeloma patients
      (p=0.001). After 3 months of ZA therapy, no significant differences were observed
      in GCF and serum RANKL and OPG levels when compared with baseline. A negative
      correlation was observed between serum control RANKL and OPG levels in myeloma
      patients. OPG levels were greater in patients with 5 or more bone metastases. In
      patients diagnosed with multiple myeloma, GCF OPG levels were negatively
      associated with WBC and platelet counts.

PMID- 24448977
TI  - Who should be admitted to the intensive care unit? The outcome of intensive care
      unit admission in stage IIIB-IV lung cancer patients.
AB  - Critical care for advanced lung cancer patients is still controversial, and the
      appropriate method for the selection of patients who may benefit from intensive
      care unit (ICU) care is not clearly defined. We retrospectively reviewed the
      medical records of stage IIIB-IV lung cancer patients admitted to the medical ICU
      of a university hospital in Korea between 2003 and 2011. Of 95 patients, 64 (67%)
      had Eastern Cooperative Oncology Group (ECOG) performance status (PS)>=2, and 79
      (84%) had non-small-cell lung cancer. In total, 28 patients (30%) were newly
      diagnosed or were receiving first-line treatment, and 22 (23%) were refractory or
      bedridden. Mechanical ventilation was required in 85 patients (90%), and ICU
      mortality and hospital mortality were 57 and 78%, respectively. According to a
      multivariate analysis, a PaO2/FiO2 ratio<150 [odds ratio (OR)=5.51, 95%
      confidence interval (CI) 2.10-14.48, p=0.001] was independently associated with
      ICU mortality, and an ECOG PS>=2 (OR=9.53, 95% CI 2.03-44.85, p=0.004) and a need
      for vasoactive agents (OR=6.94, 95% CI 1.61-29.84, p=0.009) were independently
      associated with hospital mortality. Refractory or bedridden patients (n=22)
      showed significantly poorer overall survival (11.0 vs. 29.0 days, p=0.005). Among
      21 patients who were discharged from the hospital, 11 (52%) received further
      chemotherapy. Certain advanced lung cancer patients may benefit from ICU
      management. However, refractory patients and patients with a poor PS do not seem
      to benefit from ICU care. Oncologists should try to discuss palliative care and
      end-of-life issues in advance to avoid futile care.

PMID- 24448978
TI  - Should BRCA2 mutation carriers avoid neoadjuvant chemotherapy?
AB  - BRCA2 mutation carriers typically develop luminal B breast cancers. Data on the
      effectiveness of neoadjuvant chemotherapy in these patients are limited because
      of small patient numbers and lack of prospective studies. We used our 15-year
      genetic clinic database to compare retrospectively the pathological complete
      response rates (pCR) and rates of post-chemotherapy nodal involvement among BRCA2
      carriers and BRCA1/2-negative (WT) patients with luminal B tumours, all treated
      with neoadjuvant anthracyclines+/-taxanes-based chemotherapy. Twenty-nine BRCA2
      carriers and 67 WT patients fulfilled the inclusion criteria and were analysed.
      Patients and treatment characteristics were represented. A pCR occurred in 3
      (10%) BRCA2 patients and 13 (19%) WT patients (p=0.43). Twenty (69%) BRCA2
      carriers and 34 (51%) WT patients remained node-positive at surgery (p=0.17).
      BRCA2 germline mutations are associated with a low probability of pCR and a high
      risk of axillary invasion. Alternative treatments are highly expected, and
      clinical trials are needed to set the best treatment regimen in this population.

PMID- 24448979
TI  - Low-cost, flexible, and self-cleaning 3D nanocone anti-reflection films for high
      efficiency photovoltaics.
AB  - Low-cost engineered nanotemplates are used to mold flexible nanocone anti
      reflection (AR) films. Both optical reflectance measurements and photovoltaics
      characterizations demonstrate that the flexible nanocone AR films can
      considerably suppress device front-side reflectance and thus improve the power
      conversion efficiency of high-efficiency thin-film CdTe solar cells.
      Additionally, these nanocone AR films are found to be superhydrophobic and thus
      possess self-cleaning capability. 

PMID- 24448980
TI  - Analysis of the bovine rumen microbiome reveals a diversity of Sus-like
      polysaccharide utilization loci from the bacterial phylum Bacteroidetes.
AB  - Several unique Sus-like polysaccharide utilization loci (PULs) were identified
      from bacteria resident in bovine rumen microbiomes through functional screening
      of a fosmid library. The loci were phylogenetically assigned to the genus
      Prevotella within the phylum Bacteroidetes. These findings were augmented by a
      bioinformatic re-evaluation of ruminal Prevotella genomes, revealing additional
      loci not previously reported in the literature. Analysis of Bacteroidales
      affiliated genomes reconstructed from a bovine rumen metagenome in a previous
      study further expanded the diversity of Sus-like PULs resident in this
      microbiome. Our findings suggest that Sus-like systems represent an important
      mechanism for degradation of a range of plant-derived glycans in ruminants. 

PMID- 24448981
TI  - Horizontal gene transfer and redundancy of tryptophan biosynthetic enzymes in
      dinotoms.
AB  - A tertiary endosymbiosis between a dinoflagellate host and diatom endosymbiont
      gave rise to "dinotoms," cells with a unique nuclear and mitochondrial redundancy
      derived from two evolutionarily distinct eukaryotic lineages. To examine how this
      unique redundancy might have affected the evolution of metabolic systems, we
      investigated the transcription of genes involved in biosynthesis of the amino
      acid tryptophan in three species, Durinskia baltica, Kryptoperidinium foliaceum,
      and Glenodinium foliaceum. From transcriptome sequence data, we recovered two
      distinct sets of protein-coding transcripts covering the entire tryptophan
      biosynthetic pathway. Phylogenetic analyses suggest a diatom origin for one set
      of the proteins, which we infer to be expressed in the endosymbiont, and that the
      other arose from multiple horizontal gene transfer events to the dinoflagellate
      ancestor of the host lineage. This is the first indication that these cells
      retain redundant sets of transcripts and likely metabolic pathways for the
      biosynthesis of small molecules and extend their redundancy to their two distinct
      nuclear genomes. 

PMID- 24448982
TI  - Gene content evolution in Discobid mitochondria deduced from the phylogenetic
      position and complete mitochondrial genome of Tsukubamonas globosa.
AB  - The unicellular eukaryotic assemblage Discoba (Excavata) comprises four lineages:
      the Heterolobosea, Euglenozoa, Jakobida, and Tsukubamonadida. Discoba has been
      considered as a key assemblage for understanding the early evolution of
      mitochondrial (mt) genomes, as jakobids retain the most gene-rich (i.e.,
      primitive) genomes compared with any other eukaryotes determined to date.
      However, to date, mt genome sequences have been completed for only a few groups
      within Discoba, including jakobids, two closely related heteroloboseans, and
      kinetoplastid euglenozoans. The Tsukubamonadida is the least studied lineage, as
      the order was only recently established with the description of a sole
      representative species, Tsukubamonas globosa. The evolutionary relationship
      between T. globosa and other discobids has yet to be resolved, and no mt genome
      data are available for this particular organism. Here, we use a "phylogenomic"
      approach to resolve the relationship between T. globosa, heteroloboseans,
      euglenozoans, and jakobids. In addition, we have characterized the mt genome of
      T. globosa (48,463 bp in length), which encodes 52 putative protein-coding and 29
      RNA genes. By mapping the gene repertoires of discobid mt genomes onto the well
      resolved Discoba tree, we model gene loss events during the evolution of discobid
      mt genomes. 

PMID- 24448983
TI  - Phylogenetic position of avian nocturnal and diurnal raptors.
AB  - We report three new avian mitochondrial genomes, two from widely separated groups
      of owls and a falcon relative (the Secretarybird). We then report additional
      progress in resolving Neoavian relationships in that the two groups of owls do
      come together (it is not just long-branch attraction), and the Secretarybird is
      the deepest divergence on the Accipitridae lineage. This is now agreed between
      mitochondrial and nuclear sequences. There is no evidence for the monophyly of
      the combined three groups of raptors (owls, eagles, and falcons), and again this
      is agreed by nuclear and mitochondrial sequences. All three groups (owls,
      accipitrids [eagles], and falcons) do appear to be members of the "higher land
      birds," and though there may not yet be full "consilience" between mitochondrial
      and nuclear sequences for the precise order of divergences of the eagles,
      falcons, and the owls, there is good progress on their relationships. 

PMID- 24448984
TI  - Anomalously enhanced hydration of aqueous electrolyte solution in hydrophobic
      carbon nanotubes to maintain stability.
AB  - An understanding of the structure and behavior of electrolyte solutions in
      nanoenvironements is crucial not only for a wide variety of applications, but
      also for the development of physical, chemical, and biological processes. We
      demonstrate the structure and stability of electrolyte in carbon nanotubes using
      hybrid reverse Monte Carlo simulations of X-ray diffraction patterns. Hydrogen
      bonds between water are adequately formed in carbon nanotubes, although some
      hydrogen bonds are restricted by the interfaces of carbon nanotubes. The hydrogen
      bonding network of water in electrolyte in the carbon nanotubes is further
      weakened. On the other hand, formation of the ion hydration shell is
      significantly enhanced in the electrolyte in the carbon nanotubes in comparison
      to ion hydration in bulk electrolyte. The significant hydrogen bond and hydration
      shell formation are a result of gaining stability in the hydrophobic
      nanoenvironment. 

PMID- 24448985
TI  - [Socioeconomic status and inflammatory biomarkers of cardiovascular diseases: How
      do education, occupation and income operate?].
AB  - BACKGROUND: In light of the consistent SES gradient in cardiovascular diseases,
      current research is focusing on possible pathways through which the socioeconomic
      status (SES) may impact health. Inflammatory processes play a critical role in
      the development of cardiovascular diseases and are associated with stress.
      Therefore, they might be one psychobiological pathway explaining how the SES gets
      under the skin. Considering the different meanings of education, occupation and
      income, this article gives an overview of the association between inflammatory
      biomarkers and socioeconomic status. RESULTS: There is high evidence for
      associations between indicators of SES - education, occupation and income - and
      inflammatory biomarkers. Possible pathways are health status, health behavior and
      psychobiological processes as a result of increased exposure to psychosocial
      stress. CONCLUSIONS: The SES gradient in cardiovascular diseases reflects
      behavioral as well as physiological pathways and systemic inflammation seems to
      be involved. Low SES is associated with an increased exposure to adverse
      circumstances of life, which can trigger biological responses and result in an
      increased risk of cardiovascular diseases. Medical history taking in cardiology
      should focus on socio-structural exposures and thereby reflect the different
      meanings of education, occupation and income.

PMID- 24448987
TI  - Response to letter regarding article, "Intraoperative magnesium administration
      does not improve neurocognitive function after cardiac surgery".

PMID- 24448986
TI  - Genome-wide association study identifies a new SMAD7 risk variant associated with
      colorectal cancer risk in East Asians.
AB  - Genome-wide association studies (GWAS) of colorectal cancer (CRC) have been
      conducted primarily in European descendants. In a GWAS conducted in East Asians,
      we first analyzed approximately 1.7 million single-nucleotide polymorphisms
      (SNPs) in four studies with 1,773 CRC cases and 2,642 controls. We then selected
      66 promising SNPs for replication and genotyped them in three independent studies
      with 3,612 cases and 3,523 controls. Five SNPs were further evaluated using data
      from four additional studies including up to 3,290 cases and 4,339 controls. SNP
      rs7229639 in the SMAD7 gene was found to be associated with CRC risk with an odds
      ratio (95% confidence interval) associated with the minor allele (A) of 1.22
      (1.15-1.29) in the combined analysis of all 11 studies (p = 2.93 * 10(-11) ). SNP
      rs7229639 is 2,487 bp upstream from rs4939827, a risk variant identified
      previously in a European-ancestry GWAS in relation to CRC risk. However, these
      two SNPs are not correlated in East Asians (r(2)  = 0.008) nor in Europeans (r(2)
      = 0.146). The CRC association with rs7229639 remained statistically significant
      after adjusting for rs4939827 as well as three additional CRC risk variants
      (rs58920878, rs12953717 and rs4464148) reported previously in this region. SNPs
      rs7229639 and rs4939827 explained approximately 1% of the familial relative risk
      of CRC in East Asians. This study identifies a new CRC risk variant in the SMAD7
      gene, further highlighting the significant role of this gene in the etiology of
      CRC.

PMID- 24448988
TI  - Prevention opportunities for oral contraceptive-associated ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Literature suggests a small increased risk of ischemic
      stroke with oral contraception (OC) use. We evaluated the association of stroke
      and OC use in women on the basis of whether they recalled being advised by a
      physician not to use OC or to discontinue OC use because of the presence of
      stroke risk modifiers, and whether such advice resulted in behavioral change.
      METHODS: A total of 572 women (224 strokes and 348 controls) aged 15 to 49 years
      were interviewed about OC use and risk modifiers, including cigarette smoking and
      headaches, among others. RESULTS: The adjusted odds ratio for OC use and stroke
      was 2.00 (95% confidence interval, 1.29-3.09). The association of OC use with
      stroke was stronger in women that reported receiving doctor's advice against OC
      use because of the presence of other stroke risk modifiers (odds ratio, 3.12; 95%
      confidence interval, 1.62-6.00) than in women who did not recall receiving such
      advice (odds ratio, 1.31; 95%confidence interval, 0.71-2.43). Of 256 women who
      recalled being advised by their doctor not to start OC or to discontinue OC use
      because of the presence of other stroke risk modifiers, 24% were still on OC at
      the time of stroke or interview. CONCLUSIONS: We confirm that certain medical
      conditions increase the risk of stroke during OC use and demonstrate the
      importance of physician counseling in those using OC in the setting of concurrent
      high-risk conditions and the need for improved patient compliance with such
      counseling.

PMID- 24448989
TI  - Response to letter regarding article, "Serum alkaline phosphatase and phosphate
      in cerebral atherosclerosis and functional outcomes after cerebral infarction".

PMID- 24448990
TI  - Letter by Tsuda regarding article, "Serum alkaline phosphatase and phosphate in
      cerebral atherosclerosis and functional outcomes after cerebral infarction".

PMID- 24448991
TI  - Reducing sodium intake to prevent stroke: time for action, not hesitation.

PMID- 24448992
TI  - Homocysteine as a predictor of early neurological deterioration in acute ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Hyperhomocysteinemia is a well-known risk factor for
      vascular disease. However, its action, mechanism, and role in the acute phase of
      stroke have not been determined. We tried to determine whether an association
      existed between elevated serum homocysteine levels and early neurological
      deterioration (END) in patients with acute ischemic stroke. METHODS: We performed
      a secondary analysis from the Cilostazol in Acute Ischemic Stroke Treatment
      (CAIST) trial, which was a double-blinded, randomized, multicenter trial,
      assessing the noninferiority of cilostazol over aspirin within 48 hours of an
      acute ischemic stroke. END was defined as an increase of >=1 point in motor power
      or an increase of >=2 points in the total National Institute of Health Stroke
      Scale score within 7 days. RESULTS: The mean (+/-SD) serum homocysteine level was
      11.4+/-4.7 MUmol/L. Of the 396 patients studied, 57 (14.4%) patients worsened
      during the 7 days after inclusion. Most (68%) of the END cases occurred within
      the first 24 hours after treatment. High levels (>10.3 MUmol/L) of serum
      homocysteine were independent predictors for END (third quartile odds ratio,
      3.45; 95% confidence intervals, 1.25-9.50; P=0.016; fourth quartile odds ratio,
      3.36; 95% confidence intervals 1.18-9.52; P=0.023) in multivariate analysis.
      CONCLUSIONS: Patients with acute stroke with elevated serum homocysteine levels
      are at an increased risk for END.

PMID- 24448993
TI  - Letter by Derakhshan regarding article, "Intraoperative magnesium administration
      does not improve neurocognitive function following cardiac surgery".

PMID- 24448994
TI  - Interactions of interventional antiarrhythmic therapies with individual diseases
      and their substrate: the next challenge in improving patient outcomes.

PMID- 24448995
TI  - From simplicity towards complexity: the Italian multidimensional approach to
      obesity.
AB  - Obesity is the result of a complex interplay among several factors leading to
      medical, functional and psychosocial consequences that markedly reduce life
      expectancy and impair quality of life. Is obesity itself a disease? Is obesity a
      brain disease? Who should treat obesity? This paper is a narrative review aimed
      to describe and to argue the prevalent position of some major Italian scientific
      and academic institutions dealing with obesity. According to the recent
      statements and recommendations published by the Italian Society for Obesity (SIO)
      and the Italian Society for the Study of Eating Disorders (SISDCA), the
      management of obese patients should include five main levels of care: (1) primary
      care, (2) outpatient treatment, (3) intensive outpatient treatment, (4)
      residential rehabilitative treatment, and (5) hospitalization. Ideally, patients
      suffering from obesity need a multidimensional evaluation intended to design an
      individualized treatment plan applying different procedures and therapeutic
      strategies (diet, physical activity and functional rehabilitation, educational
      therapy, cognitive-behavior therapy, drug therapy, and bariatric surgery). This
      thorough approach should address not only weight loss but also quality of weight
      loss, medical and psychiatric comorbidity, psychosocial problems, and physical
      disability. Such management of obesity requires an effective multiprofessional
      team, while health services have to overcome a number of administrative and
      organizational barriers that do not account for diseases requiring resources and
      professionals from different areas of medicine. Integrating several competences
      in a team-based approach demands specific education, skills and expertise. As for
      other diseases, the principles of complexity theory may offer a model useful to
      implement both teamwork and care delivery for patients with obesity. 

PMID- 24448996
TI  - Adaptation of the ORTHO-15 test to Polish women and men.
AB  - OBJECTIVE: There is a lack of Polish tools to measure behaviour related to
      orthorexia nervosa. The purpose of the present study was to validate the Polish
      version of the ORTHO-15 test. METHODS: 341 women and 59 men (N = 400) were
      recruited, whose age ranged from 18 to 35 years. Mean age was 23.09 years (SD =
      3.14) in women and 24.02 years (SD = 3.87) in men. The ORTHO-15 test and the EAT
      26 test were used in the present study. RESULTS: Factor analysis (exploratory and
      confirmatory analysis) was used in the present study. Exploratory factor analysis
      performed on the initial 15 items from a random split half of the study group
      suggested a nine-item two-factor structure. Confirmatory factor analysis
      performed on the second randomly selected half of the study group supported this
      two-factor structure of the ORTHO-15 test. The Polish version of the ORTHO-15
      test demonstrated an internal consistency (Cronbach's alpha) equal to 0.644.
      CONCLUSION: The Polish version of the ORTHO-15 test is a reliable and valuable
      instrument to assess obsessive attitudes related to healthy and proper nutrition
      in Polish female and male population.

PMID- 24448997
TI  - Postpancreatectomy hemorrhage--incidence, treatment, and risk factors in over
      1,000 pancreatic resections.
AB  - BACKGROUND: Postpancreatectomy hemorrhage is a rare but often severe complication
      after pancreatic resection. The aim of this retrospective study was to define
      incidence and risk factors of postpancreatectomy hemorrhage and to evaluate
      treatment options and outcome. PATIENTS AND METHODS: Clinical data was extracted
      from a prospectively maintained database. Descriptive statistics, univariate and
      multivariate risk factor analysis by binary logistic regression were performed
      with SPSS software at a significance level of p = 0.05. RESULTS: N = 1,082
      patients with pancreatic resections between 1994 and 2012 were included.
      Interventional angiography was successful in about half of extraluminal bleeding.
      A total of 78 patients (7.2 %) had postpancreatectomy hemorrhage (PPH), and 29
      (2.7 %) were grade C PPH. Multivariate modeling disclosed a learning effect, age,
      BMI, male sex, intraoperative transfusion, portal venous and multivisceral
      resection, pancreatic fistula and preoperative biliary drainage as independent
      predictors of severe postpancreatectomy hemorrhage. High-risk histopathology,
      age, transfusion, pancreatic fistula, postpancreatectomy hemorrhage and
      pancreatojejunostomy in pancreatoduodenectomies were independent predictors of
      mortality. CONCLUSIONS: Our study identifies clinically relevant risk factors for
      postpancreatectomy hemorrhage and mortality. Interventional treatment of
      extraluminal hemorrhage is successful in about half of the cases and if
      unsuccessful constitutes a valuable adjunct to operative hemostasis. Based on our
      observations, we propose a treatment scheme for PPH. Risk factor analysis
      suggests appropriate patient selection especially for extended resections and
      pancreatogastrostomy for reconstruction in pancreatoduodenectomy.

PMID- 24448998
TI  - Uncinate duct dilation in intraductal papillary mucinous neoplasms of the
      pancreas: a radiographic finding with potentially increased malignant potential.
AB  - BACKGROUND: Risk of high-grade dysplasia and invasive carcinoma in intraductal
      papillary mucinous neoplasms (IPMN) of the pancreas is increased in main duct
      compared to branch duct lesions. We hypothesized that isolated uncinate duct
      dilation may also be a radiographic indicator of high-risk disease, as the
      primary drainage of this portion of the gland originates from a distinct
      embryologic precursor. METHODS: All patients with available preoperative imaging
      who underwent resection for IPMN between 1994 and 2010 were included (n = 184).
      Imaging studies were reviewed by an experienced radiologist who was blinded to
      the pathologic results, and studies were categorized as main duct, branch duct,
      or combined-duct. The presence of uncinate duct dilation was assessed as a risk
      factor for tumors which proved to have high-grade dysplasia (HGD) or invasive
      carcinoma (IC) on pathologic assessment. RESULTS: IPMN with HGD or IC were
      identified in 82 of 184 cases (45%). Without considering uncinate duct dilation,
      IPMN with HGD or IC were present in 84% of patients with main duct IPMN (n =
      31/37), 58% with combined-duct IPMN (n = 23/40), and 26% with branch ?duct IPMN
      (n = 28/107). Dilation of the uncinate duct was observed in 47 patients, with or
      without main duct dilation, and 30 of these (64%) contained HGD or IC on
      pathology. Isolated uncinate duct dilation without main duct dilation was
      observed in 17 patients, and 11 (65%) had HGD. On multivariate analysis of IPMN
      without associated main duct dilation, uncinate duct dilation was independently
      associated with IPMN with HGD or IC (p = 0.002). CONCLUSION: Uncinate duct
      dilation on preoperative radiologic imaging appears to be an additional risk
      factor for IPMN-associated high-grade dysplasia or adenocarcinoma.

PMID- 24448999
TI  - Pathologic grade and tumor size are associated with recurrence-free survival in
      patients with duodenal neuroendocrine tumors.
AB  - BACKGROUND: Duodenal neuroendocrine tumors are rare and few studies exist to
      guide surgical management. This study identifies factors associated with
      recurrence after resection. METHODS: A retrospective, single institution review
      was performed between 1983 and 2011 on patients with a pathologic diagnosis of
      duodenal neuroendocrine tumor. Tumor grade was assigned based on WHO 2010
      criteria (Ki-67 and mitotic rate). RESULTS: Seventy-five patients were identified
      that underwent curative resection. This included 12 patients with endoscopic
      mucosal resection, 34 that had local resection, and 29 that underwent
      pancreaticoduodenectomy. Two-year and 5-year recurrence-free survival was 84 and
      81%, respectively. There were 11 tumor recurrences (either local or distant), and
      four patients died of their disease (3/4 had high-grade lesions) with an overall
      median follow-up of 27 months. On univariate analysis, tumor size and tumor grade
      were identified as being associated with recurrence, but not intervention type,
      lymph node metastases, ampullary location, or margin status. CONCLUSIONS: Tumor
      grade and size are associated with recurrence-free survival in duodenal
      neuroendocrine tumors. When feasible, a less aggressive surgical approach to
      treat low-grade and low-stage duodenal NETs should be considered.

PMID- 24449000
TI  - Non-neoplastic epithelial cysts of the pancreas: a rare, benign entity.
AB  - OBJECTIVES: With the increased use of cross-sectional radiologic imaging in
      recent years, cystic lesions of the pancreas are being diagnosed with greater
      frequency. While pseuodocysts have historically accounted for the majority of
      benign pancreatic cysts, there are a number of rare, benign cystic lesions of the
      pancreas that can mimic neoplastic cysts. The objective of this study was to
      review a single institution's experience with these benign cystic lesions of the
      pancreas. METHODS: We conducted a retrospective analysis of all patients who
      underwent surgical resection for pancreatic disease from 2005 to 2012 at our
      institution. Out of a total of 947 pancreatic resections, we identified those
      cases performed for cystic disease, and focused upon the clinicopathologic data
      of patients with non-neoplastic pancreatic cysts. RESULTS: Of the 947 pancreatic
      resections, 256 (27%) were performed for cystic disease. Sixteen cases (6.3%) out
      of the total of 256 pancreatic operations performed for cystic disease were found
      to have non-neoplastic cystic lesions of the pancreas. Preoperative imaging
      revealed primary lesions in all patients, eight of which were found incidentally.
      Of these lesions, 14 were suspected preoperatively to be mucinous neoplasms and
      two to harbor pancreatic adenocarcinoma. However, postoperative pathology
      revealed eight patients with ductal retention cysts, three squamoid cysts, one
      mucinous non-neoplastic cyst, one congenital ciliated foregut cyst, one
      lymphoepithelial cyst, and two endometrial cysts. Two patients had complications
      postoperatively, one pancreatic fistula and one SMV thrombosis. Both
      complications resolved with conservative management. CONCLUSIONS: Non-neoplastic
      epithelial pancreatic cysts are rare, benign lesions. In our institutional
      experience, these lesions are often indistinguishable from cystic neoplasms of
      the pancreas preoperatively. As such, many of these lesions are resected
      unknowingly. It is important for the clinician to be well informed of the nature
      of these lesions, in the hopes to avoid unnecessary resection whenever possible.

PMID- 24449001
TI  - Long-term outcomes of laparoscopic surgery for advanced transverse colon cancer.
AB  - BACKGROUND: The role of laparoscopic surgery for advanced transverse colon cancer
      (TCC) remains controversial, especially in terms of long-term oncologic outcomes.
      METHODS: This retrospective cohort study enrolled 157 consecutive patients who
      underwent curable resections for advanced TCC between January 2002 and June 2011
      (laparoscopic-assisted colectomy (LAC), n = 74; open colectomy (OC), n = 83).
      Short-term outcomes and oncologic long-term outcomes were compared between the
      two groups. RESULTS: Compared to the OC group, patients in the LAC group had less
      blood loss (LAC vs. OC, 79.6 +/- 70.3 vs. 158.4 +/- 89.3 ml, p < 0.001), faster
      return of bowel function (2.6 +/- 0.7 vs. 3.8 +/- 0.8 days, p < 0.001), and
      shorter postoperative hospital stay (10.3 +/- 3.7 vs. 12.6 +/- 6.0 days, p =
      0.007). Conversions were required in four (5.4%) patients. Rates of short-term
      complication, mortality, and long-term complication were comparable between the
      two groups. The median follow-up time was 54 (26-106) months in the LAC group and
      58 (29-113) months in the OC group (p = 0.407). There were no statistical
      differences in the rates of 5-year overall survival (73.6 vs. 71.1%, p = 0.397)
      and 5-year disease-free survival (70.5 vs. 66.7%, p = 0.501) between the two
      groups. CONCLUSIONS: Laparoscopic surgery for advanced TCC yield short-term
      benefits while achieving equivalent long-term oncologic outcomes.

PMID- 24449002
TI  - Accuracy of a proximal tibial cutting method using the anterior tibial border in
      TKA.
AB  - PURPOSE: In conventional total knee arthroplasty (TKA) using extramedullary
      alignment guides, it is not always easy to cut the proximal tibia precisely
      perpendicular to the tibial axis. The purpose of this study was to compare the
      radiographic accuracy of cutting the proximal tibia between the use of the bony
      landmarks of the anterior tibial border and the use of the conventional
      technique. METHODS: A total of 173 patients underwent primary TKA. In 76 TKAs, we
      used the bony landmark method, and in 97 TKAs, we used the conventional method.
      In the bony landmark method, we set the coronal alignment in reference to the
      line connecting the proximal and distal one-third of the anterior tibial border,
      and we determined the 5 degrees  posterior slope in reference to this line. Six
      months postoperatively, radiological evaluations were performed using full-length
      standing anteroposterior and lateral radiographs of the knee. RESULTS: No
      significant differences in the coronal tibial component angle were found between
      the groups. The posterior tilt of the tibial component was significantly smaller
      in the bony landmark method than in the conventional method (5.1 degrees  +/- 2.9
      degrees  vs. 6.4 degrees  +/- 3.2 degrees , respectively; p = 0.007). The
      percentage of patients whose posterior tilt of the tibial component was within +/
      3 degrees  of 5 degrees  was significantly larger in the bony landmark method
      than in the conventional method (70 vs. 62%, respectively; p = 0.04).
      CONCLUSIONS: The bony landmark method provided a more accurate posterior tibial
      slope than the conventional method. However, there was no difference in coronal
      alignment compared with the conventional method.

PMID- 24449003
TI  - Biomechanical effects of pedicle screw fixation on adjacent segments.
AB  - Various biomechanical investigations have attempted to clarify the aetiology of
      adjacent segment disease (ASD). However, no biomechanical study has examined in
      detail the deformation behaviour of the adjacent segments when both pure torque
      and an angular displacement load are applied to the vertebrae along multiple
      segments. The purpose of this study is to investigate the biomechanical effects
      of pedicle screw fixation on adjacent segments. Ten cadaveric lumbar spines (L2
      L5) of boars were used. Control and fusion models were prepared by disc damage
      and pedicle screw fixation of each specimen, and then, bending and rotation tests
      were performed using a six-axis material tester. In the biomechanical tests
      regulated by an angular displacement load, the range of motion (ROM) of the
      cranial and caudal adjacent segments in antero-posterior flexion and lateral
      bending was increased by about 20 % (p < 0.05), and the maximal torque in the
      fusion model was about threefold (p < 0.05) that in the control model. And in
      axial rotation, the ROM of cranial and caudal adjacent segments was increased by
      about 100 % (p < 0.001), and the maximal torque was about sixfold (p < 0.01) that
      in the control model. The ROM of adjacent segments was significantly increased
      after pedicle screw fixation as assessed by biomechanical tests regulated by an
      angular displacement load, but not in those regulated by torque. We present the
      results of biomechanical tests regulated by torque and angular displacement and
      show that the maximum torque of the fusion model was larger than that of the
      control model in the biomechanical test regulated by an angular displacement
      load, suggesting that mechanical stress on the segments adjacent to the fused
      segment is large. We think that ASD arises after spinal fusion surgery as a
      mechanism to compensate for the ROM lost due to excessive fusion by pedicle screw
      fixation, so that a large torque may be applied to adjacent segments within a
      physiologically possible range, and it might gradually lead to a degenerative
      intervertebral disc or progression of spondylolisthesis in the adjacent segments.

PMID- 24449004
TI  - Concise review: MicroRNAs as modulators of stem cells and angiogenesis.
AB  - MicroRNAs (miRs) are highly conserved, short noncoding RNA molecules that
      negatively regulate messenger RNA (mRNA) stability and/or translational
      efficiency. Since a given miR can control the expression of many mRNAs, their
      importance in governing gene expression in specific cell types including vascular
      cells and their progenitor cells has become increasingly clear. Understanding how
      the expression of miRs themselves is regulated and how miRs exert their influence
      on post-transcriptional gene control provides novel opportunities to dissect gene
      regulatory networks in clinically relevant cell types. A multitude of miRs have
      been identified with key roles in vascular development, homeostasis, function,
      disease, and regeneration. In this review, we will describe the impact of miRs on
      angiogenesis and their capacity to modulate the behavior of stem and progenitor
      cells which may be utilitarian for promoting vascular growth in ischemic tissue.
      Moreover, we summarize these strategies available for modulating miR expression
      and function and future therapeutic applications.

PMID- 24449006
TI  - The effect of aging on anticipatory postural control.
AB  - The aim of the study was to investigate the differences in anticipatory postural
      adjustments (APAs) between young and older adults and its effect on subsequent
      control of posture. Ten healthy older adults and thirteen healthy young adults
      were exposed to predictable external perturbations using the pendulum impact
      paradigm. Electromyographic activity of the trunk and leg muscles, the center of
      pressure (COP), and center of mass (COM) displacements in the anterior-posterior
      direction were recorded and analyzed during the anticipatory and compensatory
      postural adjustments (CPAs) phases of postural control. The effect of aging was
      seen as delayed anticipatory muscle activity and larger compensatory muscle
      responses in older adults as compared to young adults. Moreover, in spite of such
      larger reactive responses, older adults were still more unstable, exhibiting
      larger COP and COM peak displacements after the perturbation than young adults
      when exposed to similar postural disturbances. Nonetheless, while APAs are
      impaired in older adults, the ability to recruit muscles anticipatorily is
      largely preserved; however, due to their smaller magnitudes and delayed onsets,
      it is likely that their effectiveness in reducing the magnitude of CPAs is
      smaller. The outcome of the study lends support toward investigating the ways of
      improving anticipatory postural control in people with balance impairments due to
      aging or neurological disorders. 

PMID- 24449005
TI  - Unmasking the dichoptic mask by sound: spatial congruency matters.
AB  - People tend to look toward where a sound occurs; however, the role of spatial
      congruency between sound and sight in the effect of sound facilitation on visual
      detection remains controversial. We propose that the role of spatial congruency
      depends on the reliability of the information provided by the facilitator; if it
      is relatively unreliable, adding spatially congruent information can help to
      unify different sensory inputs to compensate for this unreliability. To test
      this, we examine the influence of sound location on visual detection with a non
      temporal task, presumably unfavorable for sound since it is better for temporal
      resolution, and predict that spatial congruency should matter in this situation.
      We used the continuous flash suppression paradigm that makes the visual stimuli
      invisible to keep the relationship of sound and sight opaque. The sound is on the
      same depth plane as the visual stimulus (the congruent condition) or on a
      different plane (the incongruent condition). The target was presented to one eye
      with luminance contrast gradually increased and continuously masked by flashed
      Mondrian masks presented to the other eye until the target was released from
      suppression. We found that sound facilitated visual detection (measured by
      released-from-suppression time) in the spatially congruent condition but not in
      the spatially incongruent condition. Together with previous findings in the
      literature, it is suggested that both task type and modality determine the
      reliability of the information for multisensory integration and thus determine
      whether spatial congruency is critical. 

PMID- 24449007
TI  - Sensory electrical stimulation improves foot placement during targeted stepping
      post-stroke.
AB  - Proper foot placement is vital for maintaining balance during walking, requiring
      the integration of multiple sensory signals with motor commands. Disruption of
      brain structures post-stroke likely alters the processing of sensory information
      by motor centers, interfering with precision control of foot placement and
      walking function for stroke survivors. In this study, we examined whether
      somatosensory stimulation, which improves functional movements of the paretic
      hand, could be used to improve foot placement of the paretic limb. Foot placement
      was evaluated before, during, and after application of somatosensory electrical
      stimulation to the paretic foot during a targeted stepping task. Starting from
      standing, twelve chronic stroke participants initiated movement with the non
      paretic limb and stepped to one of five target locations projected onto the floor
      with distances normalized to the paretic stride length. Targeting error and lower
      extremity kinematics were used to assess changes in foot placement and limb
      control due to somatosensory stimulation. Significant reductions in placement
      error in the medial-lateral direction (p = 0.008) were observed during the
      stimulation and post-stimulation blocks. Seven participants, presenting with a
      hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude
      and duration of hip abduction during swing with somatosensory stimulation.
      Reductions in circumduction correlated with both functional and clinical
      measures, with larger improvements observed in participants with greater
      impairment. The results of this study suggest that somatosensory stimulation of
      the paretic foot applied during movement can improve the precision control of
      foot placement.

PMID- 24449008
TI  - Neural correlates of adaptation to gradual and to sudden visuomotor distortions
      in humans.
AB  - This study aimed at scrutinizing the neural correlates of sensorimotor
      adaptation. Subjects were exposed either to a gradually (group G) or to a
      suddenly introduced perturbation (group S) followed by a test of aftereffects.
      They were also exposed to a control condition equated for their movement errors
      during the adaptation condition. We registered subjects' brain activity by
      functional magnetic resonance imaging. Behavioral data revealed no difference
      between aftereffects in G and S, while imaging data suggest different neural
      correlates. Direct comparison between groups showed more adaptation-related
      activation in left cingulate and inferior frontal as well as right caudate and
      temporal areas in S than in G. In contrast, no neural activity was related more
      to G than to S and no common activations were found for both groups. Within-group
      analyses further revealed right inferior parietal lobe, cerebellar and cingulate
      cortex activity in group S and activation of frontal lobe and left cerebellum in
      group G for a contrast between adaptation condition and baseline. Less brain
      activity was observed when controlled for movement errors: the contrast between
      adaptation and control condition yielded left occipital lobe activity in group S,
      and left posterior dentate nucleus and brainstem activity in group G. The present
      data confirm an involvement of the cerebellar cortex in error processing during
      sudden adaptation, since this activation was found for the contrast 'adaptation
      baseline' but not for 'adaptation-control.' In addition, our data suggest an
      involvement of deep cerebellar nuclei in the adaptation to gradually introduced
      distortions. 

PMID- 24449009
TI  - Free-field study on auditory localization and discrimination performance in older
      adults.
AB  - Localization accuracy and acuity for low- (0.375-0.75 kHz; LN) and high-frequency
      (2.25-4.5 kHz; HN) noise bands were examined in young (20-29 years) and older
      adults (65-83 years) in the acoustic free-field. A pointing task was applied to
      quantify accuracy, while acuity was inferred from minimum audible angle (MAA)
      thresholds measured with an adaptive 3-alternative forced-choice procedure.
      Accuracy decreased with laterality and age. From young to older adults, the
      accuracy declined by up to 23 % for the low-frequency noise band across all
      lateralities. The mean age effect was even more pronounced on MAA thresholds.
      Thus, age was a strong predictor for MAA thresholds for both LN and HN bands.
      There was no significant correlation between hearing status and localization
      performance. These results suggest that central auditory processing of space
      declines with age and is mainly driven by age-related changes in the processing
      of binaural cues (interaural time difference and interaural intensity difference)
      and not directly induced by peripheral hearing loss. We conclude that the
      representation of the location of sound sources becomes blurred with age as a
      consequence of declined temporal processing, the effect of which becomes
      particularly evident for MAA thresholds, where two closely adjoining sound
      sources have to be separated. While localization accuracy and MAA were not
      correlated in older adults, only a weak correlation was found in young adults.
      These results point to an employment of different processing strategies for
      localization accuracy and acuity.

PMID- 24449010
TI  - The effects of social housing on extinction of fear conditioning in rapid eye
      movement sleep-deprived rats.
AB  - Both human and animal research indicate that rapid eye movement sleep (REM) plays
      an important role in the processing of emotional information. REM is altered
      after fear conditioning in rats, but this alteration can be mitigated by exposure
      to a naive conspecific. In addition, both the housing condition (isolated vs
      paired) and the experiences of rats' cagemates can influence the response to
      aversive events. Based on this prior work, the present study sought to determine
      the effects of social housing on the previously demonstrated impairment in the
      extinction of conditioned fear responses produced by REM deprivation. Rats were
      assigned to one of three housing conditions: housed with a naive rat, housed with
      another fear-conditioned rat, or housed alone. The results demonstrated that rats
      housed with either a naive or a fear-conditioned conspecific exhibited an
      impairment in the acquisition of extinction as a consequence of REM deprivation,
      as observed in previous studies. However, rats in the isolated condition
      demonstrated a trend toward an impairment only after continued extinction
      training. These results indicate that the effects of social housing on REM
      deprivation-induced impairments in learning and memory are subtle, but may
      explain some conflicting findings in the literature.

PMID- 24449012
TI  - Spontaneous postural sway predicts the strength of smooth vection.
AB  - This study asked whether individual differences in the influence of vision on
      postural stability could be used to predict the strength of subsequently induced
      visual illusions of self-motion (vection). In the experiment, we first measured
      spontaneous postural sway while subjects stood erect for 60 s with their eyes
      both open and both closed. We then showed our subjects two types of self-motion
      display: radially expanding optic flow (simulating constant velocity forwards
      self-motion) and vertically oscillating radially expanding optic flow (simulating
      constant velocity forwards self-motion combined with vertical head oscillation).
      As expected, subjects swayed more with their eyes closed (compared to open) and
      experienced more compelling illusions of self-motion with vertically oscillating
      (as opposed to smooth) radial flow. The extent to which participants relied on
      vision for postural stability-measured as the ratio of sway with eyes closed
      compared to that with eyes open-was found to predict vection strength. However,
      this was only the case for displays representing smooth self-motion. It seems
      that for oscillating displays, other factors, such as visual-vestibular
      interactions, may be more important.

PMID- 24449011
TI  - Sleep and the processing of emotions.
AB  - How emotions interact with cognitive processes has been a topic of growing
      interest in the last decades, as well as studies investigating the role of sleep
      in cognition. We review here evidence showing that sleep and emotions entertain
      privileged relationships. The literature indicates that exposure to stressful and
      emotional experiences can induce changes in the post-exposure sleep architecture,
      whereas emotional disturbances are likely to develop following sleep alterations.
      In addition, post-training sleep appears particularly beneficial for the
      consolidation of intrinsically emotional memories, suggesting that emotions
      modulate the off-line brain activity patterns subtending memory consolidation
      processes. Conversely, sleep contributes unbinding core memories from their
      affective blanket and removing the latter, eventually participating to
      habituation processes and reducing aversive reactions to stressful stimuli. Taken
      together, these data suggest that sleep plays an important role in the regulation
      and processing of emotions, which highlight its crucial influence on human's
      abilities to manage and respond to emotional information. 

PMID- 24449013
TI  - Auditory-motor integration of subliminal phase shifts in tapping: better than
      auditory discrimination would predict.
AB  - Unilateral tapping studies have shown that adults adjust to both perceptible and
      subliminal changes in phase or frequency. This study focuses on the phase
      responses to abrupt/perceptible and gradual/subliminal changes in auditory-motor
      relations during alternating bilateral tapping. We investigated these responses
      in participants with and without good perceptual acuity as determined by an
      auditory threshold test. Non-musician adults (nine per group) alternately tapped
      their index fingers in synchrony with auditory cues set at a frequency of 1.4 Hz.
      Both groups modulated their responses (with no after-effects) to perceptible and
      to subliminal changes as low as a 5 degrees  change in phase. The high-threshold
      participants were more variable than the adults with low threshold in their
      responses in the gradual condition set. Both groups demonstrated a
      synchronization asymmetry between dominant and non-dominant hands associated with
      the abrupt condition and the later blocks of the gradual condition. Our findings
      extend previous work in unilateral tapping and suggest (1) no relationship
      between a discrimination threshold and perceptible auditory-motor integration and
      (2) a noisier sub-cortical circuitry in those with higher thresholds.

PMID- 24449014
TI  - Exploring the world with Balint syndrome: biased bottom-up guidance of gaze by
      local saliency differences.
AB  - Balint syndrome is a combination of severe deficits affecting spatial attention,
      visuo-motor control and oculomotor function. While the severe restriction of
      attention (simultanagnosia) and impairments of visually guided reaching have been
      extensively studied, oculomotor apraxia has received comparatively little
      attention. The main explanatory hypothesis of oculomotor apraxia is that it is a
      direct consequence of the severe restriction of attention. Here, we examined in a
      patient with Balint syndrome to what extent local image features such as
      luminance and contrast predict whether a region will be fixated or not. During
      the viewing of natural photographs, the patient made saccades of very small
      amplitude, but showed strongly increased fixation duration. In addition, the
      horizontal and vertical range of fixations was severely restrained compared to
      control subjects. When analysing the local feature content at fixation, we found
      that central fixations of the patient contained less local luminance and contrast
      than fixations of controls while he made fixations to peripheral image regions
      with disproportionately high luminance and contrast. These findings suggest that
      while our patient gazes at central regions irrespective of their local feature
      content, he only looks to the periphery when his gaze is captured by particularly
      conspicuous features. We propose that oculomotor apraxia in Balint syndrome
      reflects a combination of biased representations within a parietal priority map
      and increased fixational activity due to biased interactions within the
      oculomotor network. 

PMID- 24449015
TI  - The effects of immediate vision on implicit hand maps.
AB  - Perceiving the external spatial location of the limbs using position sense
      requires that immediate proprioceptive afferent signals be combined with a stored
      body model specifying the size and shape of the body. Longo and Haggard (Proc
      Natl Acad Sci USA 107:11727-11732, 2010) developed a method to isolate and
      measure this body model in the case of the hand in which participants judge the
      perceived location in external space of several landmarks on their occluded hand.
      The spatial layout of judgments of different landmarks is used to construct
      implicit hand maps, which can then be compared with actual hand shape. Studies
      using this paradigm have revealed that the body model of the hand is massively
      distorted, in a highly stereotyped way across individuals, with large
      underestimation of finger length and overestimation of hand width. Previous
      studies using this paradigm have allowed participants to see the locations of
      their judgments on the occluding board. Several previous studies have
      demonstrated that immediate vision, even when wholly non-informative, can alter
      processing of somatosensory signals and alter the reference frame in which they
      are localised. The present study therefore investigated whether immediate vision
      contributes to the distortions of implicit hand maps described previously.
      Participants judged the external spatial location of the tips and knuckles of
      their occluded left hand either while being able to see where they were pointing
      (as in previous studies) or while blindfolded. The characteristic distortions of
      implicit hand maps reported previously were clearly apparent in both conditions,
      demonstrating that the distortions are not an artefact of immediate vision.
      However, there were significant differences in the magnitude of distortions in
      the two conditions, suggesting that vision may modulate representations of body
      size and shape, even when entirely non-informative. 

PMID- 24449016
TI  - Transgenerational occurrence of allergic disease and autoimmunity: general
      practice-based epidemiological research.
AB  - BACKGROUND: Corresponding with the T helper cell type 1/T helper cell type 2
      hypothesis, autoimmune and allergic diseases are considered pathologically
      distinct and mutually exclusive conditions. Co-occurrence of autoimmune disorders
      and allergy within patients, however, has been reported. Transgenerational co
      occurrence of autoimmune and allergic disease has been less often described and
      may differ from the intra-patient results. AIMS: To test the hypothesis that
      autoimmune disorders in parents are a risk factor for the development of an
      allergic disease in their offspring. METHODS: Prospectively registered (by
      academic general practitioners) International Classifications of Primary Care
      (ICPC) for diagnoses of autoimmune disorders and allergy within families were
      evaluated (n=5,604 families) by performing multiple logistic regression analyses.
      RESULTS: The presence of any ICPC-encoded autoimmune disorder in fathers appeared
      to be associated with an increased risk in their eldest children of developing an
      allergy (odds ratio (OR) 1.4, 95% CI 1.042 to 1.794). Psoriasis in fathers was
      particularly shown to be of influence (OR 1.5, 95% CI 1.061 to 2.117) and,
      although any ICPC-encoded autoimmune disease in mothers was found not to be of
      significance, the combined international code for registering rheumatoid
      arthritis/ankylosing spondylitis in mothers was OR 1.7 (95% CI 1.031 to 2.852).
      CONCLUSIONS: The occurrence of ICPC-encoded autoimmune disorders in parents,
      especially psoriasis and rheumatoid arthritis/ankylosing spondylitis,
      significantly increases the occurrence of allergic disease in their children.
      After validation in follow-up research in a larger sample, these results may lead
      to the inclusion of 'parental autoimmune condition' as a risk factor in the
      general practitioner's diagnostics of allergic disease.

PMID- 24449017
TI  - Are GOLD ABCD groups better associated with health status and costs than GOLD
      1234 grades? A cross-sectional study.
AB  - AIMS: To investigate the association of the GOLD ABCD groups classification with
      costs and health-related quality of life (HR-QoL) and to compare this with the
      GOLD 1234 grades classification that was primarily based on lung function only.
      METHODS: In a cross-sectional study, we selected patients diagnosed with chronic
      obstructive pulmonary disease (COPD) from electronic medical records of general
      practices. Multi-level analysis was used with costs (medication, primary care,
      healthcare, societal), diseasespecific and generic HR-QoL as independent
      variables. Either the new or the old GOLD stages were included in the analysis
      together with several covariates (age, gender, living situation, co-morbidity,
      self-efficacy, smoking, education, employment). RESULTS: 611 patients from 28
      general practices were categorised as GOLD-A (n=333), GOLD-B (n=110), GOLD-C
      (n=80) and GOLD-D (n=88). Patients in the GOLD-B and GOLD-D groups had the
      highest prevalence of co-morbidities and the lowest level of physical activity,
      self-efficacy, and employment. The models with GOLD ABCD groups were more
      strongly related to and explained more variance in costs and in disease-specific
      and generic HR-QoL than the models with GOLD 1234 grades. The mean Clinical COPD
      Questionnaire score worsened significantly, with scores 1.04 (GOLD-B), 0.4 (GOLD
      C) and 1.21 (GOLD-D) worse than for patients in GOLD-A. Healthcare costs per
      patient were significantly higher in GOLD-B (72%), GOLD-C (74%) and GOLD-D (131%)
      patients than in GOLD-A patients. CONCLUSIONS: The GOLD ABCD groups
      classification is more closely associated with costs and HR-QoL than the GOLD
      1234 grades classification. Furthermore, patients with GOLD-C had a better HR-QoL
      than those with GOLD-B but the costs of the two groups did not differ.

PMID- 24449018
TI  - Aesthetic outcomes in women undergoing breast-conserving therapy followed by
      mastectomy and microsurgical reconstruction.
AB  - BACKGROUND: In women with early-stage breast cancer, breast-conserving therapy
      (BCT) provides comparable survival to mastectomy. BCT has the advantage of
      preserving most of the breast, its skin envelope and the nipple-areola complex.
      However, deformity may result from the excision of significant amounts of breast
      tissue, as well as radiation therapy. Several studies have compared patients who
      underwent BCT to different patients who underwent mastectomy and reconstruction,
      and found superior aesthetic outcomes in the latter group. Our goal in this study
      was to compare the aesthetic outcomes in the same women who underwent BCT
      followed by mastectomy and reconstruction. METHODS: Between 2007 and 2012, 42
      women with a history of BCT developed cancer recurrence and underwent mastectomy
      and microsurgical breast reconstruction at our institution. Photographs before
      and after mastectomy and reconstruction were rated by a panel of nine judges (two
      independent plastic surgeons, three surgical oncologists, one radiation
      oncologist, one medical oncologist, and two medical students), using a validated
      scale RESULTS: Overall, patients received a significantly higher aesthetic score
      after mastectomy and reconstruction than after BCT. The greatest areas of
      aesthetic improvement were breast volume, contour, and projection. Patients whose
      lumpectomy was in the lower inner quadrant, those undergoing bilateral mastectomy
      and reconstruction and those completing all stages of their reconstruction had
      the greatest aesthetic improvement CONCLUSIONS: When advising patients with early
      stage breast cancer, the superior aesthetic outcome of mastectomy and
      microsurgical reconstruction compared to BCT must be weighed against
      disadvantages such as loss of sensation, length of surgery, and donor-site
      morbidity.

PMID- 24449019
TI  - Body size and activity times mediate mammalian responses to climate change.
AB  - Model predictions of extinction risks from anthropogenic climate change are dire,
      but still overly simplistic. To reliably predict at-risk species we need to know
      which species are currently responding, which are not, and what traits are
      mediating the responses. For mammals, we have yet to identify overarching
      physiological, behavioral, or biogeographic traits determining species' responses
      to climate change, but they must exist. To date, 73 mammal species in North
      America and eight additional species worldwide have been assessed for responses
      to climate change, including local extirpations, range contractions and shifts,
      decreased abundance, phenological shifts, morphological or genetic changes. Only
      52% of those species have responded as expected, 7% responded opposite to
      expectations, and the remaining 41% have not responded. Which mammals are and are
      not responding to climate change is mediated predominantly by body size and
      activity times (phylogenetic multivariate logistic regressions, P < 0.0001).
      Large mammals respond more, for example, an elk is 27 times more likely to
      respond to climate change than a shrew. Obligate diurnal and nocturnal mammals
      are more than twice as likely to respond as mammals with flexible activity times
      (P < 0.0001). Among the other traits examined, species with higher latitudinal
      and elevational ranges were more likely to respond to climate change in some
      analyses, whereas hibernation, heterothermy, burrowing, nesting, and study
      location did not influence responses. These results indicate that some mammal
      species can behaviorally escape climate change whereas others cannot, analogous
      to paleontology's climate sheltering hypothesis. Including body size and activity
      flexibility traits into future extinction risk forecasts should substantially
      improve their predictive utility for conservation and management. 

PMID- 24449020
TI  - 30 Years of sodium/X-nuclei magnetic resonance imaging.
AB  - In principle, all nuclei with nonzero spin can be employed for magnetic resonance
      imaging (MRI). Special scanner hardware and MR sequences are required to select
      the nucleus-specific frequency and to enable imaging with "sufficient" signal-to
      noise ratio. This Special Issue starts with an overview of different nuclei that
      can be used for MRI today, followed by a review article about techniques required
      for imaging of quadrupolar nuclei with short relaxation times. Sequence
      developments to improve image quality and applications on different organs and
      diseases are presented for different nuclei ((23)Na, (35)Cl, (17)O, and (19)F),
      with a focus on imaging at natural abundance. 

PMID- 24449022
TI  - Emergency escape surgery for a gastro-bronchial fistula with respiratory failure
      that developed after esophagectomy.
AB  - A gastro-bronchial fistula (GBF) is a rare complication after esophageal
      reconstruction using a gastric tube, but it can cause severe pneumonia, and the
      surgical procedure is challenging. We herein describe a patient who was
      successfully managed using a two-stage operation for a GBF. Because the patient
      had life-threatening pneumonia and respiratory failure caused by the GBF, we
      first transected the duodenum, established a cervical esophagostomy and
      gastrostomy and placed a decompression catheter in the gastric tube without a
      thoracotomy. The patient recovered from pneumonia after the resolution of the
      salivary inflow and digestive juice reflux into the lungs through the GBF. Two
      months later, an esophageal bypass was achieved by reconstructing the esophagus
      using a long segment of pedicled jejunum. The patient was discharged 38 days
      thereafter. Appropriate treatment for GBF should be tailored to individual
      patients based on their current status and disease severity.

PMID- 24449023
TI  - Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A:
      report of a case.
AB  - We report a rare case with pheochromocytoma as the first manifestation of
      multiple endocrine neoplasia type 2A with RET mutation S891A. Bilateral
      pheochromocytomas were identified in a 54-year-old woman. Screening for RET
      revealed a rare S891A mutation located in the intracellular tyrosine kinase
      domain. This mutation was previously recognized as one of the mutations only in
      cases manifesting solely medullary thyroid carcinomas (MTCs). Since calcitonin
      stimulation test indicated positive result, total thyroidectomy was performed 1
      year after the bilateral adrenalectomy, and C-cell hyperplasia was diagnosed by
      histopathological examination. Our report suggests that cases with S891A
      mutation, akin to those with other RET mutations, require screening for
      pheochromocytoma. In addition, it is indicated that calcitonin stimulation test
      should be performed even in the unaffected elder cases with S891A mutation
      although the mutation is classified as lowest risk group on MTC in guidelines.

PMID- 24449025
TI  - In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L
      lysine and poly-L-lysine/poly-L-glutamate in rats.
AB  - The combination of two differently charged polypeptides, poly-L-lysine (PL) and
      poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties.
      However, the high molecular, positively charged PL is toxic in high doses,
      proposed as lysis of red blood cells. This study aims to elucidate the in vivo
      toxicity and biodistribution of PL and complex bound PLPG comparing intravenous
      and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a
      model with repeated blood samples within 30 min examining blood gases and blood
      smears. Similarly, FITC labelled PL were used to track bio distribution and
      clearance of PL, given as single dose and complex bound to PG after intravenous
      and intraperitoneal administration. Tissue for histology and immunohistochemistry
      was collected. Blood gases and blood smears as well as histology points to a
      toxic effect of high dose PL given intravenously but not after intraperitoneal
      administration. The toxic effect is exerted through endothelial disruption and
      subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled
      PL experiments reveal a rapid clearance with differences between routes and
      complex binding. This study advocates a new theory of the toxic effects in vivo
      of high molecular PL. PLPG complex is safe to use as antiadhesive prevention
      based on this toxicity study given that PL is always intraperitoneally
      administered in combination with PG and that the dose is adequate.

PMID- 24449024
TI  - Sterilizing tissue-materials using pulsed power plasma.
AB  - This paper investigates the potential of pulsed power to sterilize hard and soft
      tissues and its impact on their physico-mechanical properties. It hypothesizes
      that pulsed plasma can sterilize both vascular and avascular tissues and the
      transitive layers in between without deleterious effects on their functional
      characteristics. Cartilage/bone laminate was chosen as a model to demonstrate the
      concept, treated at low temperature, at atmospheric pressure, in short durations
      and in buffered environment using a purposed-built pulsed power unit. Input
      voltage and time of exposure were assigned as controlling parameters in a full
      factorial design of experiment to determine physical and mechanical alteration
      pre- and post-treatment. The results demonstrated that, discharges of 11 kV
      sterilized samples in 45 s, reducing intrinsic elastic modules from 1.4 +/- 0.9
      to 0.9 +/- 0.6 MPa. There was a decrease of 14.1 % in stiffness and 27.8 % in
      elastic-strain energy for the top quartile. Mechanical impairment was directly
      proportional to input voltage (P value < 0.05). Bacterial inactivation was
      proportional to treatment time for input voltages above 32 V (P < 0.001; R Sq =
      0.98). Thermal analysis revealed that helix-coil transition decelerated with
      exposure time and collagen fibrils were destabilized as denaturation enthalpy
      reduced by 200 MUV. We concluded by presenting a safe operating threshold for
      pulsed power plasma as a feasible protocol for effective sterilization of
      connective tissues with varying level of loss in mechanical robustness which we
      argue to be acceptable in certain medical and tissue engineering application.

PMID- 24449027
TI  - Cytotoxic, hematologic and histologic effects of niobium pentoxide in Swiss mice.
AB  - The use of metal devices in medical application is increasing but it remains
      incompletely understood the physiological effects of component degradation.
      Niobium (Nb) alloys have already been investigated in the 1980's and recent
      studies demonstrated the potential of Nb as an implant material. The purpose of
      this study was to determine cytotoxic, hematologic and histologic effects of
      niobium in Swiss mice. Animals were treated with a single dose of 3 % niobium
      oxide (Nb2O5) diluted in PBS, i.p. Cytotoxic assay, hematologic and histologic
      evaluation were done 3, 7 and 12 days after niobium treatment. Data have shown
      increased number of cells after niobium treatment, but there was no difference in
      cell viability. Furthermore, it was not observed hematological modification 3, 7
      or 12 days after niobium treatment. Despite the fact that animals treated with
      niobium for 3 and 7 days showed mild degeneration in hepatocytes, mice kept alive
      for 12 days showed liver cells regeneration. Our results suggested that niobium
      cytotoxicity was not progressive because 12 days after treatment there was an
      evident liver regeneration. Data obtained indicated that niobium may be promising
      alternatives to biomedical applications.

PMID- 24449026
TI  - Evaluation of various silver-containing dressing on infected excision wound
      healing study.
AB  - Silver-containing dressings have been widely used for controlling wound
      infection. However, the relationship between different concentrations of silver
      in dressings and their antimicrobial activities and wound-healing efficacies
      remains unclear. In the present study, we (in cooperation with Bio-medical Carbon
      Technology) investigated various silver-containing activated carbon fibers to
      understand the effects of different silver concentrations on the efficacies of a
      silver containing dressing. Our results indicated that various silver-containing
      activated carbon fibers exhibited good antibacterial effects and biocompatibility
      in terms of cell viability and that silver concentration showed a minor influence
      on cell growth. The infected excision wound model indicated that compared to
      silver-containing activated carbon fiber and other commercial silver-containing
      dressings assisted wound healing by promoting granulation and collagen
      deposition. Meanwhile, the silver ion can only be restrained in epidermis by
      intact skin. During application on the wound area, a temporary increase of serum
      silver can be detected, but this elevated serum silver level decreased to a
      subtle level after the removal of silver-containing activated carbon fiber.

PMID- 24449028
TI  - Optimizing the concentration of quaternary ammonium dimethacrylate monomer in bis
      GMA/TEGDMA dental resin system for antibacterial activity and mechanical
      properties.
AB  - Four novel quaternary ammonium dimethacrylate monomers named IMQ (side alkyl
      chain length from 12 to 18) were synthesized with the aim to synthesize dental
      resin with antibacterial activity. All of IMQs were added into bis-GMA/TEGDMA
      dental resin system with a series of mass ratio (5, 10, and 20 wt%), double bond
      conversion (DC), flexural strength (FS), modulus of elasticity (FM) and biofilm
      formation inhibitory effect were studied. According to the results of DC, FS, FM,
      and the biofilm inhibitory effect, IMQ-16 containing polymer had the best
      comprehensive properties, and the optimal concentration of IMQ-16 in bis
      GMA/TEGDMA dental resin would be in the range of 5-10 wt%.

PMID- 24449030
TI  - Two-color RESOLFT nanoscopy with green and red fluorescent photochromic proteins.
AB  - Up to now, all demonstrations of reversible saturable optical fluorescence
      transitions (RESOLFT) superresolution microscopy of living cells have relied on
      the use of reversibly switchable fluorescent proteins (RSFP) emitting in the
      green spectral range. Here we show RESOLFT imaging with rsCherryRev1.4, a new red
      emitting RSFP enabling a spatial resolution up to four times higher than the
      diffraction barrier. By co-expressing green and red RSFPs in living cells we
      demonstrate two-color RESOLFT imaging both for single ("donut") beam scanning and
      for parallelized versions of RESOLFT nanoscopy where an array of >23,000 "donut
      like" minima are scanned simultaneously.

PMID- 24449031
TI  - Acceptance and commitment therapy versus cognitive behavioral therapy in the
      treatment of substance use disorder with incarcerated women.
AB  - OBJECTIVES: This randomized controlled study compared acceptance and commitment
      therapy (ACT), cognitive-behavioral therapy (CBT), and a control group. METHOD:
      The participants were 50 incarcerated women diagnosed with current substance use
      disorder. Two psychologists carried out pre- and posttreatment assessment and a 6
      month follow-up assessment using the following instruments: Anxiety Sensitivity
      Index, Addiction Severity Index-6, Mini International Neuropsychiatric Interview,
      and Acceptance and Action Questionnaire. RESULTS: The study shows that the women
      who received treatment benefited differentially from the interventions. At
      posttreatment, CBT was more effective than ACT in reducing anxiety sensitivity;
      however, at follow-up, ACT was more effective than CBT in reducing drug use (43.8
      vs. 26.7%, respectively) and improving mental health (26.4% vs. 19.4%,
      respectively). CONCLUSION: ACT may be an alternative to CBT for treatment of drug
      abuse and associated mental disorders. In fact, at long-term, ACT may be more
      appropriate than CBT for incarcerated women who present serious problems.

PMID- 24449033
TI  - SMART designs in observational studies of opioid therapy duration.

PMID- 24449032
TI  - Intervention to improve care at life's end in inpatient settings: the BEACON
      trial.
AB  - BACKGROUND: Widespread implementation of palliative care treatment plans could
      reduce suffering in the last days of life by adopting best practices of
      traditionally home-based hospice care in inpatient settings. OBJECTIVE: To
      evaluate the effectiveness of a multi-modal intervention strategy to improve
      processes of end-of-life care in inpatient settings. DESIGN: Implementation trial
      with an intervention staggered across hospitals using a multiple-baseline,
      stepped wedge design. PARTICIPANTS: Six Veterans Affairs Medical Centers (VAMCs).
      INTERVENTION: Staff training was targeted to all hospital providers and focused
      on identifying actively dying patients and implementing best practices from home
      based hospice care, supported with an electronic order set and paper-based
      educational tools. MAIN MEASURES: Several processes of care were identified as
      quality endpoints for end-of-life care (last 7 days) and abstracted from
      electronic medical records of veterans who died before or after intervention (n =
      6,066). Primary endpoints were proportion with an order for opioid pain
      medication at time of death, do-not-resuscitate order, location of death,
      nasogastric tube, intravenous line infusing, and physical restraints. Secondary
      endpoints were administration of opioids, order/administration of antipsychotics,
      benzodiazepines, and scopolamine (for death rattle); sublingual administration;
      advance directives; palliative care consultations; and pastoral care services.
      Generalized estimating equations were conducted adjusting for longitudinal
      trends. KEY RESULTS: Significant intervention effects were observed for orders
      for opioid pain medication (OR: 1.39), antipsychotic medications (OR: 1.98),
      benzodiazepines (OR: 1.39), death rattle medications (OR: 2.77), sublingual
      administration (OR: 4.12), nasogastric tubes (OR: 0.71), and advance directives
      (OR: 1.47). Intervention effects were not significant for location of death, do
      not-resuscitate orders, intravenous lines, or restraints. CONCLUSIONS: This
      broadly targeted intervention strategy led to modest but statistically
      significant changes in several processes of care, indicating its potential for
      widespread dissemination to improve end-of-life care for thousands of patients
      who die each year in inpatient settings.

PMID- 24449034
TI  - Capsule commentary on Grant, et al., Exercise as a vital sign: a quasi
      experimental analysis of a health system intervention to collect patient-reported
      exercise levels.

PMID- 24449035
TI  - Capsule commentary on Stephens et al., Who needs inpatient detox? Development and
      implementation of a hospitalist protocol for the evaluation of patients for
      alcohol detoxification.

PMID- 24449036
TI  - Highly sensitive, uniform, and reproducible surface-enhanced Raman spectroscopy
      from hollow Au-Ag alloy nanourchins.
AB  - A hierarchical nanoparticle strategy to simultaneously gain super Raman signal
      amplification, high uniformity, and reproducibility is presented. Using hollow Au
      Ag alloy nanourchins, an ultrahigh sensitivity, e.g., down to 1 fM concentrations
      for DEHP molecule is obtained. A small standard deviation of <10% is achieved by
      simply dropping and evaporating sub-100 nm nanourchins onto a substrate. 

PMID- 24449037
TI  - Focus on the patentability of computer programs.
AB  - The Nuts and Bolts section of our Journal (mirrored on the ICCNS society web
      site), is meant to provide a very practical way to share useful information, that
      goes beyond the scope of cell signaling and basic CCN protein biology.
      Considering the number of requests we have had for information related to
      protection of Intellectual Property (IP), I am pleased to initiate what will be a
      series of articles that will focus on various IP topics. The inaugural topic is
      the protection of computer programs. Some colleagues may wonder how and why the
      patentability of computer programs is a topic of interest for scientists working
      on CCN proteins . . . As a matter of fact, to assist us in analyzing the
      potential involvement of CCN3 in human genetic diseases, we considered developing
      a computer program designed to analyze large amounts of data. Sharing the
      concepts and the computer program raised concerns regarding IP and protection of
      the software that we would handle. We believe that many colleagues have
      encountered similar problems. This article provides a short focus on computer
      program patentability. It is aimed to provide basic legal information, and to
      help our readers in understanding the process. It is not intended to replace IP
      counselors or technology transfer departments. Future articles will address other
      practical aspects of IP protection. 

PMID- 24449038
TI  - Pharmacological treatment of vascular risk factors for reducing mortality and
      cardiovascular events in patients with abdominal aortic aneurysm.
AB  - BACKGROUND: Pharmacological prophylaxis has been proven to reduce the risk of
      cardiovascular events in patients with atherosclerotic occlusive arterial
      disease. However, the role of prophylaxis in patients with abdominal aortic
      aneurysm (AAA) remains unclear. Several studies have shown that despite
      successful repair, those with AAA have a poorer rate of survival than healthy
      controls. People with AAA have an increased prevalence of coronary heart disease
      and risk of cardiovascular events. Despite this association, little is known
      about the effectiveness of pharmacological prophylaxis in reducing cardiovascular
      risk in people with AAA. OBJECTIVES: To determine the long-term effectiveness of
      antiplatelet, antihypertensive or lipid-lowering medication in reducing mortality
      and cardiovascular events in people with abdominal aortic aneurysm (AAA). SEARCH
      METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co
      ordinator searched the Specialised Register (last searched April 2013) and
      CENTRAL (2013, Issue 3). Reference lists of relevant articles were also checked.
      SELECTION CRITERIA: Randomised controlled trials in which people with AAA were
      randomly allocated to one prophylactic treatment versus another, a different
      regimen of the same treatment, a placebo, or no treatment were eligible for
      inclusion in this review. Primary outcomes included all-cause mortality and
      cardiovascular mortality. DATA COLLECTION AND ANALYSIS: Selection of the studies,
      quality assessment and data extraction were completed independently by two review
      authors. Any disagreements were resolved by discussion. Only one study was
      included in the review, therefore meta-analysis could not be performed. MAIN
      RESULTS: One randomised controlled study was included in the review. A subgroup
      of 227 patients with AAA received either metoprolol (N = 111) or placebo (N =
      116). There was no clear evidence that metoprolol reduced all-cause mortality
      (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.02 to 1.41), cardiovascular
      death (OR 0.20, 95% CI 0.02 to 1.76), AAA-related death (OR 1.05, 95% CI 0.06 to
      16.92) or increased nonfatal cardiovascular events (OR 1.44, 95% CI 0.58 to 3.57)
      30 days postoperatively. Furthermore, at six months postoperatively, estimated
      effects were compatible with benefit and harm for all-cause mortality (OR 0.71,
      95% CI 0.26 to 1.95), cardiovascular death (OR 0.73, 95% CI 0.23 to 2.39) and
      nonfatal cardiovascular events (OR 1.41, 95% CI 0.59 to 3.35). Adverse drug
      effects were reported for the whole study population and were not available for
      the subgroup of participants with AAA. The study was deemed to be at a generally
      low risk of bias. AUTHORS' CONCLUSIONS: Due to the limited number of trials,
      there is insufficient evidence to draw any conclusions about the effectiveness of
      cardiovascular prophylaxis in reducing mortality and cardiovascular events in
      people with AAA. Further good-quality randomised controlled trials examining many
      types of prophylaxis with long-term follow-up are required before firm
      conclusions can be made.

PMID- 24449039
TI  - Effects of Person-Centered Care Approaches to Dementia Care on Staff: A
      Systematic Review.
AB  - Person-centered care (PCC) has been the subject of several intervention studies
      reporting positive effects on people with dementia. However, its impact on staff
      remains unclear. The purpose of this systematic review was to assess the impact
      of PCC approaches on stress, burnout, and job satisfaction of staff caring for
      people with dementia in residential aged care facilities. Research articles
      published up to 2013 were searched on PubMed, Web of Knowledge, Scopus, and EBSCO
      and reference lists from relevant publications. The review was limited to
      experimental and quasi-experimental studies, published in English and involving
      direct care workers (DCWs). In all, 7 studies were included, addressing different
      PCC approaches: dementia care mapping (n=1), stimulation-oriented approaches
      (n=2), emotion-oriented approaches (n=2), and behavioral-oriented approaches
      (n=2). Methodological weaknesses and heterogeneity among studies make it
      difficult to draw firm conclusions. However, 5 studies reported benefits on DCWs,
      suggesting a tendency toward the effectiveness of PCC on staff.

PMID- 24449041
TI  - Morphological clocks in paleontology, and a mid-Cretaceous origin of crown Aves.

PMID- 24449040
TI  - Mitochondrial variation among the Aymara and the signatures of population
      expansion in the central Andes.
AB  - OBJECTIVES: The exploitation of marine resources and intensive agriculture led to
      a marked population increase early in central Andean prehistory. Constant
      historic and prehistoric population movements also characterize this region.
      These features undoubtedly affected regional genetic variation, but the exact
      nature of these effects remains uncertain. METHODS: Mitochondrial DNA (mtDNA)
      hypervariable region I sequence variation in 61 Aymara individuals from La Paz,
      Bolivia, was analyzed and compared to sequences from 47 other South American
      populations to test hypotheses of whether increased female effective population
      size and gene flow influenced the mtDNA variation among central Andean
      populations. RESULTS: The Aymara and Quechua were genetically diverse showing
      evidence of population expansion and large effective population size, and a
      demographic expansion model fits the mtDNA variation found among central Andean
      populations well. Estimated migration rates and the results of AMOVA and
      multidimensional scaling analysis suggest that female gene flow was also an
      important factor, influencing genetic variation among the central Andeans as well
      as lowland populations from western South America. mtDNA variation in south
      central Andes correlated better with geographic proximity than with language, and
      fit a population continuity model. CONCLUSION: The mtDNA data suggests that the
      central Andeans experienced population expansion, most likely because of rapid
      demographic expansion after introduction of intensive agriculture, but roles of
      female gene flow need to be further explored.

PMID- 24449042
TI  - Interleukin 6 mediates the therapeutic effects of adipose-derived stromal/stem
      cells in lipopolysaccharide-induced acute lung injury.
AB  - Adipose-derived stromal/stem cells (ASCs) have anti-inflammatory as well as
      immunosuppressive activities and are currently the focus of clinical trials for a
      number of inflammatory diseases. Acute lung injury (ALI) is an inflammatory
      condition of the lung for which standard treatment is mainly supportive due to
      lack of effective therapies. Our recent studies have demonstrated the ability of
      both human ASCs (hASCs) and mouse ASCs (mASCs) to attenuate lung damage and
      inflammation in a rodent model of lipopolysaccharide-induced ALI, suggesting that
      ASCs may also be beneficial in treating ALI. To better understand how ASCs may
      act in ALI and to elucidate the mechanism(s) involved in ASC modulation of lung
      inflammation, gene expression analysis was performed in ASC-treated (hASCs or
      mASCs) and control sham-treated lungs. The results revealed a dramatic difference
      between the expression of anti-inflammatory molecules by hASCs and mASCs. These
      data show that the beneficial effects of hASCs and mASCs in ALI may result from
      the production of different paracrine factors. Interleukin 6 (IL-6) expression in
      the mASC-treated lungs was significantly elevated as compared to sham-treated
      controls 20 hours after delivery of the cells by oropharyngeal aspiration.
      Knockdown of IL-6 expression in mASCs by RNA interference abrogated most of their
      therapeutic effects, suggesting that the anti-inflammatory properties of mASCs in
      ALI are explained, at least in part, by activation of IL-6 secretion.

PMID- 24449043
TI  - Multipolar electrostatics for proteins: atom-atom electrostatic energies in
      crambin.
AB  - Accurate electrostatics necessitates the use of multipole moments centered on
      nuclei or extra point charges centered away from the nuclei. Here, we follow the
      former alternative and investigate the convergence behavior of atom-atom
      electrostatic interactions in the pilot protein crambin. Amino acids are cut out
      from a Protein Data Bank structure of crambin, as single amino acids, di, or
      tripeptides, and are then capped with a peptide bond at each side. The atoms in
      the amino acids are defined through Quantum Chemical Topology (QCT) as finite
      volume electron density fragments. Atom-atom electrostatic energies are computed
      by means of a multipole expansion with regular spherical harmonics, up to a total
      interaction rank of L = lA+ lB + 1 = 10. The minimum internuclear distance in the
      convergent region of all the 15 possible types of atom-atom interactions in
      crambin that were calculated based on single amino acids are close to the values
      calculated from di and tripeptides. Values obtained at B3LYP/aug-cc-pVTZ and
      MP2/aug-cc-pVTZ levels are only slightly larger than those calculated at HF/6
      31G(d,p) level. This convergence behavior is transferable to the well-known
      amyloid beta polypeptide Abeta1-42. Moreover, for a selected central atom, the
      influence of its neighbors on its multipole moments is investigated, and how far
      away this influence can be ignored is also determined. Finally, the convergence
      behavior of AMBER becomes closer to that of QCT with increasing internuclear
      distance.

PMID- 24449044
TI  - Origin of the "endo rule" in Diels-Alder reactions.
AB  - Detailed density functional theory calculations definitively rationalize the
      preference for the endo cycloadduct (also known as endo rule) in text-book
      thermal Diels-Alder reactions involving maleic anhydride and cyclopentadiene or
      butadiene. This selectivity is mainly caused by an unfavorable steric arrangement
      in the transition-state region of the exo pathway which translates into a more
      destabilizing activation strain. In contrast with the widely accepted, orbital
      interaction-based explanation for the endo rule, it is found that neither the
      orbital interactions nor the total interaction between the deformed reactants
      contributes to the endo selectivity.

PMID- 24449049
TI  - Evidence-based medicine--an oral history.

PMID- 24449050
TI  - The calcium supplement controversy: now what?

PMID- 24449051
TI  - Design and mechanical properties of a novel cerebral flow diverter stent.
AB  - Brain arterial aneurysms are localised dilatation in the wall of cerebral
      arteries that are common among adult population and associated with high
      incidence of morbidity and mortality. Using flow diverter stent alone to treat
      cerebral aneurysm is recognized as a safe and effective method. However, flow
      diverter stents currently available have limitations due to their braided
      structures. In this paper a novel flow diverter stent is proposed. It is made out
      of nitinol tubes that provide adequate radial stiffness and tailored surface
      coverage to overcome problems of currently available braided stents while
      retaining low porosity and excellent longitudinal flexibility. Finite element
      analysis using Abaqus has been conducted to investigate radial stiffness,
      longitudinal flexibility, and maximum strain during packaging of a series of
      novel stent designs with varied geometric parameters. Results show that porosity
      below 70% can be achieved and provides radial stiffness and longitudinal
      flexibility comparable to those of the Neuroform stent that is commonly used for
      stent assisted coiling. The novel flow diverter has showed great potential for
      direct treatment of cerebral aneurysms. 

PMID- 24449052
TI  - A nanoengineered embolic agent for precise radiofrequency ablation.
AB  - The purpose of the work is to investigate whether the electromagnetic properties
      of multi-walled carbon nanotubes (MWCNT) in the presence of radiofrequency (RF)
      energy is (1) safe, and (2) improves the precision of the therapeutic efficiency
      of the RF-ablation (RFA) procedure. An in vitro phantom was created for
      evaluating temperature near RF treated nanotubes. For the in vivo study, three
      baboons and six pigs were submitted for RFA procedure in superior/inferior kidney
      poles embolized with a non-adherent, lipophilic embolic agent (marsembol) with or
      without MWCNT. Tissue damage in the surrounding kill zone was assayed through
      caspase-3 activation. The in vitro results showed marked heat increase only in
      the region of the nanotubes. In vivo, necrosis/ischemic damage resulted from RFA
      therapy alone, RFA plus marsembol only. In marsembol + MWCNT condition, dramatic
      disruption of cell membranes and sub-cellular organelles was found whereas the
      nuclear membranes and basal cell membranes remained largely intact. The marsembol
      vaporized under RFA and tissue fluid filled the space. This caused the MWCNT to
      cluster within the new aqueous environment. RFA plus marsembol + MWCNT created a
      well-defined demarcation between healthy and apoptotic cells as evidenced by a
      marked reduction of caspase-3 expression. By contrast, there was a much less
      defined ablation zone in the absence of MWCNT. In conclusion, the combination of
      RFA plus marsembol + MWCNT embolization delineated the kill zone in vitro and in
      vivo. We demonstrate that MWCNTs remain in the ablation region thus minimizing
      their migration to the systemic circulation. 

PMID- 24449053
TI  - Teaching the structure of immunoglobulins by molecular visualization and SDS-PAGE
      analysis.
AB  - This laboratory class combines molecular visualization and laboratory
      experimentation to teach the structure of the immunoglobulins (Ig). In the first
      part of the class, the three-dimensional structures of the human IgG and IgM
      molecules available through the RCSB PDB database are visualized using freely
      available software. In the second part, IgG and IgM are studied using
      electrophoretic methods. Through SDS-PAGE analysis under reducing conditions, the
      students determine the number and molecular masses of the polypeptide chains,
      while through SDS-PAGE under nonreducing conditions, the students assess the
      oligomerization of these Ig molecules. The aims of this class are to expand upon
      the knowledge and understanding of the Ig structure that the students have gained
      from classroom lectures. The combination of this molecular visualization of the
      Ig molecules and the SDS-PAGE experimentation ensures variety in the teaching
      techniques, while the implication of the Ig molecules in human disease promotes
      interest for biomedical students.

PMID- 24449054
TI  - Size-dependent phase transformation of catalytically active nanoparticles
      captured in situ.
AB  - The utilization of metal nanoparticles traverses across disciplines and we
      continue to explore the intrinsic size-dependent properties that make them so
      unique. Ideal nanoparticle formulation to improve a process's efficiency is
      classically presented as exposing a greater surface area to volume ratio through
      decreasing the nanoparticle size. Although, the physiochemical characteristics of
      the nanoparticles, such as phase, structure, or behavior, may be influenced by
      the nature of the environment in which the nanoparticles are subjected1, 2 and,
      in some cases, could potentially lead to unwanted side effects. The degree of
      this influence on the particle properties can be size-dependent, which is seldom
      highlighted in research. Herein we reveal such an effect in an industrially
      valuable cobalt Fischer-Tropsch synthesis (FTS) catalyst using novel in situ
      characterization. We expose a direct correlation that exists between the cobalt
      nanoparticle's size and a phase transformation, which ultimately leads to
      catalyst deactivation. 

PMID- 24449055
TI  - Piper betel leaf: a reservoir of potential xenohormetic nutraceuticals with
      cancer-fighting properties.
AB  - Plants contain a much greater diversity of bioactive compounds than any man-made
      chemical library. Heart-shaped Piper betel leaves are magnificent reservoirs of
      phenolic compounds with antiproliferative, antimutagenic, antibacterial, and
      antioxidant properties. Widely consumed in South Asian countries, the glossy leaf
      contains a multitude of biophenolics such as hydroxychavicol, eugenol,
      chavibetol, and piperols. Convincing data underscore the remarkable
      chemotherapeutic and chemopreventive potential of betel leaves against a variety
      of cancer types. The leaf constituents modulate an extensive array of signaling
      molecules such as transcription factors as well as reactive oxygen species (ROS)
      to control multiple nodes of various cellular proliferation and death pathways.
      Herein, we provide an overall perspective on the cancer-fighting benefits of the
      phenolic phytochemicals in betel leaves and a comprehensive overview of the
      mechanisms responsive to dose-driven ROS-mediated signaling cascades conscripted
      by bioactive phenolics to confer chemotherapeutic and chemopreventive advantages.
      Intriguingly, these ROS-triggered responses are contextual and may either elicit
      a protective xenohormetic antioxidant response to premalignant cells to
      constitute a chemopreventive effect or generate a curative chemotherapeutic
      response by pro-oxidatively augmenting the constitutively elevated ROS levels in
      cancer cells to tip the balance in favor of selective apoptosis induction in
      cancer cells while sparing normal ones. In conclusion, this review provides an
      update on how distinct ROS levels exist in normal versus cancer cells and how
      these levels can be strategically modulated and exploited for therapeutic gains.
      We emphasize the yet untapped potential of the evergreen vine, betel leaf, for
      chemopreventive and chemotherapeutic management of cancer.

PMID- 24449056
TI  - Benign breast and gynecologic conditions, reproductive and hormonal factors, and
      risk of thyroid cancer.
AB  - The higher incidence of thyroid cancer in women compared with men suggests an
      influence of sex steroid hormones in the etiology of this malignancy. We
      investigated a comprehensive set of potential indicators of lifetime sex steroid
      hormone exposure in relation to thyroid cancer risk. Using data from the
      Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled
      70,047 women, 50 to 78 years old, we prospectively examined associations of self
      reported history of benign breast and gynecologic conditions, reproductive
      factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable
      adjusted HRs and 95% confidence intervals (CI) were calculated in models using
      age as the time metric. During follow-up (median, 11 years), 127 women were
      diagnosed with first primary thyroid cancer. Older age at natural menopause (>=55
      vs. <50 years; HR, 2.24; 95% CI, 1.20-4.18), greater estimated lifetime number of
      ovulatory cycles (>=490 vs. <415 cycles; HR, 2.40; 95% CI, 1.33-4.30), greater
      number of live births (>=5 vs. 1-2; HR, 1.72; 95% CI, 1.05-2.82), and history of
      uterine fibroids (HR, 1.72; 95% CI, 1.18-2.50) were associated with an increased
      risk of thyroid cancer. Earlier age at menarche, greater number of reproductive
      years, history of a tubal ligation, and history of ovarian cysts were
      nonsignificantly associated with increased thyroid cancer risk. No associations
      were observed for oral contraceptive use, menopausal hormone therapy, or history
      of benign breast disease or endometriosis. In general, we found that factors
      reflecting a greater length of exposure to endogenous hormones, particularly
      during the reproductive years, were associated with risk of postmenopausal
      thyroid cancer.

PMID- 24449058
TI  - Freestanding triboelectric-layer-based nanogenerators for harvesting energy from
      a moving object or human motion in contact and non-contact modes.
AB  - For versatile mechanical energy harvesting from arbitrary moving objects such as
      humans, a new mode of triboelectric nanogenerator is developed based on the
      sliding of a freestanding triboelectric-layer between two stationary electrodes
      on the same plane. With two electrodes alternatively approached by the tribo
      charges on the sliding layer, electricity is effectively generated due to
      electrostatic induction. A unique feature of this nanogenerator is that it can
      operate in non-contact sliding mode, which greatly increases the lifetime and the
      efficiency of such devices. 

PMID- 24449057
TI  - PI3K-AKT signaling is a downstream effector of retinoid prevention of murine
      basal cell carcinogenesis.
AB  - Basal cell carcinoma (BCC) is the most common human cancer. We have demonstrated
      previously that topical application of the retinoid prodrug tazarotene profoundly
      inhibits murine BCC carcinogenesis via retinoic acid receptor gamma-mediated
      regulation of tumor cell transcription. Because topical retinoids can cause
      adverse cutaneous effects and because tumors can develop resistance to retinoids,
      we have investigated mechanisms downstream of tazarotene's antitumor effect in
      this model. Specifically we have used (i) global expression profiling to identify
      and (ii) functional cell-based assays to validate the phosphoinositide 3-kinase
      (PI3K)/AKT/mTOR pathway as a downstream target pathway of tazarotene's action.
      Crucially, we have demonstrated that pharmacologic inhibition of this downstream
      pathway profoundly reduces murine BCC cell proliferation and tumorigenesis both
      in vitro and in vivo. These data identify PI3K/AKT/mTOR signaling as a highly
      attractive target for BCC chemoprevention and indicate more generally that this
      pathway may be, in some contexts, an important mediator of retinoid anticancer
      effects.

PMID- 24449059
TI  - Lynch syndrome patients' views of and preferences for return of results following
      whole exome sequencing.
AB  - Whole exome sequencing (WES) uses next generation sequencing technology to
      provide information on nearly all functional, protein-coding regions in an
      individual's genome. Due to the vast amount of information and incidental
      findings that can be generated from this technology, patient preferences must be
      investigated to help clinicians consent and return results to patients. Patients
      (n = 19) who were previously clinically diagnosed with Lynch syndrome, but
      received uninformative negative Lynch syndrome genetic results through
      traditional molecular testing methods participated in semi-structured interviews
      after WES testing but before return of results to explore their views of WES and
      preferences for return of results. Analyses of interview results found that
      nearly all participants believed that the benefits of receiving all possible
      results generated from WES outweighed the undesirable effects. The majority of
      participants conveyed that relative to coping with a cancer diagnosis,
      information generated from WES would be manageable. Importantly, participants'
      experience with Lynch syndrome influenced their notions of genetic determinism,
      tolerance for uncertain results, and family communication plans. Participants
      would prefer to receive WES results in person from a genetic counselor or medical
      geneticist so that an expert could help explain the meaning and implications of
      the potentially large quantity and range of complicated results. These results
      underscore the need to study various populations with regard to the clinical use
      of WES in order to effectively and empathetically communicate the possible
      implications of this new technology and return results.

PMID- 24449060
TI  - The MoSt Project--more steps in multiple sclerosis: a Delphi method consensus
      initiative for the evaluation of mobility management of MS patients in Italy.
AB  - The aim of the study was to identify the main factors that impact mobility
      impairment in multiple sclerosis (MS) patients in Italy. Clinicians from a large
      number of Italian MS centers took part in a Delphi process aimed at obtaining
      consensus statements among the participants. Large consensus was obtained for
      statements grouped under the following main MS themes: identification of the most
      useful scales to evaluate mobility, integration of objective evaluation with
      patient perceptions, impact of walking impairment on daily life, management of
      the disabled patient using a rehabilitative and pharmacological approach. The
      consensus statements developed by a large number of experts may be used as a
      practical reference tool to help physicians treat MS patients with motor
      impairment. 

PMID- 24449061
TI  - The presence of oligoclonal IgG bands in human CSF during the course of
      neurological diseases.
AB  - The analysis of cerebrospinal fluid (CSF) is an important tool for the diagnosis
      of neurological diseases. However, there is limited knowledge about the
      representativity of a single oligoclonal band (OCB) analysis for a neurological
      disease during its clinical course. In this study, we analyzed the presence of
      OCB in the CSF of patients who underwent lumbar puncture more than once. We
      retrospectively analyzed anonymized data from serial 17,002 CSF analyses done in
      the CSF laboratory of the Department of Neurology, University Hospital Zurich. We
      included cases with documented diagnosis in whom OCB were determined more than
      once. We included 144 patients. The median time span between the first and second
      OCB analysis was 274 days (range, 1-3,533 days). The result of the second OCB
      analysis was identical in 109 cases, and different in 35 (24 %). Twenty-five
      patients acquired and ten patients lost OCB over time. Three of 24 MS patients
      did not show OCB at the first CSF analysis, but in the second. In the entire
      group, newly occurring OCB were often associated with new symptoms or occurred
      after the acute phase of CNS infectious diseases, supposedly as a consequence of
      the immune reaction. A loss of OCB was often associated with remissions from
      diseases, e.g., during effective treatment. In patients with neurological
      diseases, both initially positive and negative OCB results may change over time,
      which often parallels the clinical condition. Such variability must be taken into
      account for the interpretation of OCB results.

PMID- 24449062
TI  - Fetal growth restriction and birth defects with newer and older antiepileptic
      drugs during pregnancy.
AB  - The primary aim of this study was to assess the risks of fetal growth restriction
      and birth defects in children exposed prenatally to newer and older antiepileptic
      drugs, using an unselected epilepsy cohort. Deliveries recorded in the compulsory
      Medical Birth Registry of Norway 1999-2011 formed the study population. All 2,600
      children exposed to antiepileptic drugs during pregnancy were compared to all
      771,412 unexposed children born to women without epilepsy. Children of untreated
      mothers with epilepsy served as an internal control group. The main outcomes were
      small for gestational age birth weight and head circumference, and major
      congenital malformations. Children exposed to antiepileptic drugs had a moderate
      risk of growth restriction. Infants exposed to topiramate had a considerable risk
      of microcephaly (11.4 vs. 2.4 %; OR 4.8; CI 2.5-9.3) and small for gestational
      age birth weight (24.4 vs. 8.9 %; OR 3.1; 95 % CI 1.9-5.3). Carbamazepine,
      lamotrigine, levetiracetam, oxcarbazepine, gabapentin, and pregabalin had low
      malformation rates, whereas topiramate tended to have an elevated malformation
      rate. Valproate monotherapy was associated with a significant risk of birth
      defects (6.3 vs. 2.9 %; OR 2.5; CI 1.6-3.8), and specifically with septal heart
      defects and hypospadias. For mothers using valproate, the presence of major birth
      defect in one child was associated with a markedly increased risk for the
      siblings (42.9 vs. 6.7 %; OR 10.4; CI 2.3-46.7). Children of untreated mothers
      with epilepsy had malformation risk similar to the reference group. In
      conclusion, topiramate was associated with a substantial risk of fetal growth
      restriction, and possibly an increased malformation rate. Other newer-generation
      antiepileptic drugs had a low malformation rate. Valproate monotherapy had a
      significant malformation risk, especially in repeated pregnancies.

PMID- 24449063
TI  - The role of the right inferior frontal gyrus in the pathogenesis of post-stroke
      psychosis.
AB  - Psychotic symptoms have previously been reported following right hemisphere brain
      injury. We sought to identify the specific neuroanatomical basis of delusions
      following stroke by studying a series of patients with post-stroke psychosis.
      Lesion overlap analysis was conducted on three individuals with delusions
      following right hemisphere stroke. These cases were compared with a control group
      of patients with similar anatomical damage. The main outcome measures were
      presence of delusions and presence of behavioural susceptibility. The right
      inferior frontal gyrus and underlying white matter, including the superior
      longitudinal fasciculus and anterior corona radiata, were involved in all three
      cases. All three had a preexisting untreated psychiatric disorder. In contrast,
      only one of nine control cases with equivalent lesions had evidence of previous
      psychiatric disorder (p = 0.0182, Fisher's exact test), and this was being
      treated at the time of stroke. We provide clinical evidence from patients with
      structural brain lesions implicating damage to the right inferior frontal lobe in
      the generation of persistent psychosis following stroke. We suggest that
      preexisting psychiatric disease provided a behavioural susceptibility to develop
      delusions in these individuals.

PMID- 24449064
TI  - Progranulin-associated PiB-negative logopenic primary progressive aphasia.
AB  - The logopenic variant of primary progressive aphasia (lvPPA) strongly associates
      with Alzheimer's disease, but can also associate with frontotemporal lobar
      degeneration. We aimed to assess the frequency of lvPPA in patients with speech
      and language disorders without beta-amyloid deposition, and to perform detailed
      neuroimaging and genetic testing in such lvPPA patients. Seventy-six patients
      with a neurodegenerative speech and language disorder and Pittsburgh compound B
      (PiB) PET imaging demonstrating no beta-amyloid deposition were analyzed. Six
      lvPPA patients (8 %) were identified. All six underwent progranulin (GRN) gene
      testing. Structural abnormality index maps and Cortex ID analysis were utilized
      to assess individual patterns of grey matter atrophy on MRI and hypometabolism on
      18-F fluorodeoxyglucose (FDG) PET. Statistical parametric mapping was used to
      perform MRI and FDG-PET group comparisons between those with (GRN-positive) and
      without (GRN-negative) progranulin mutations. All six lvPPA patients showed left
      temporoparietal atrophy and hypometabolism. Three patients (50 %) were GRN
      positive. Speech, language, and neurological and neuropsychological profiles did
      not differ between GRN-positive and negative patients, although GRN-positive
      patients had family histories, were on average 8 years younger, and had lower PiB
      PET ratios. All six patients showed similar patterns of atrophy and
      hypometabolism, although, as a group, GRN-positive patients had more severe
      abnormalities, particularly in anteromedial temporal lobes. Logopenic PPA
      accounts for a small minority of neurodegenerative speech and language disorders
      not associated with beta-amyloid deposition. Identification of such patients,
      however, should prompt testing for GRN mutations, since GRN-positive patients do
      not have distinctive features, yet account for 50 % of this patient population.

PMID- 24449065
TI  - Psychiatric disorders in idiopathic-isolated focal dystonia.
AB  - Idiopathic-isolated focal dystonia (IIFD) is a movement disorder characterised by
      involuntary, sustained muscle contractions, leading to abnormal postures.
      Psychopathology is frequent in patients with IIFD, and while traditionally this
      was thought to be a secondary phenomenon, there is emerging evidence for shared
      neurobiological mechanisms. We conducted a single-centre cross-sectional study of
      103 consecutive patients with IIFD and two comparison groups: 78 consecutive
      patients with hemifacial spasm (HFS) and 93 healthy control subjects. Assessments
      with regard to psychiatric disturbances were performed using self-report
      questionnaires, including the self-report version of the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS-SR), the Beck Anxiety Inventory (BAI), and the Beck
      Depression Inventory (BDI). Compared to healthy control subjects and patients
      with HFS, the IIFD group had higher OCS, anxiety, and depression scores as
      measured by the Y-BOCS-SR, BAI, and BDI, respectively. The Y-BOCS-SR, BAI, and
      BDI were highly correlated across all the subjects. Logistic regression analysis
      showed that the main driver of high obsessive-compulsive symptom scores,
      irrespective of neurological diagnosis, was the BDI, whereas it was BAI (and not
      BDI), that drives the association between the psychiatric rating scale scores and
      the neurological diagnosis. Our findings suggest that while clinically
      significant obsessive-compulsive symptoms are over-represented in IIFD patients
      relative to controls, the BAI may have better discriminatory power to distinguish
      between the psychiatric symptoms in IIFD patients. 

PMID- 24449067
TI  - Leadership in an academic department of psychiatry.

PMID- 24449066
TI  - Evolution of Charcot-Marie-Tooth disease type 1A duplication: a 2-year clinico
      electrophysiological and lower-limb muscle MRI longitudinal study.
AB  - The objective of this study was to analyze Charcot-Marie-Tooth disease type 1A
      (CMT1A) evolution. We conducted a 2-year longitudinal study in 14 CMT1A patients
      and 14 age- and sex-matched controls. In the patients, we performed neurological
      examination with hand-held dynamometry, electrophysiology, and lower-limb muscle
      MRI, both at baseline and 2 years later, while controls were examined at baseline
      only. Patients' ages ranged from 12 to 51 years. Outstanding manifestations on
      initial evaluation included pes cavus, areflexia, lower-limb weakness, and foot
      hypopallesthesia. In evaluating muscle power, good correlation was observed
      between manual testing and dynamometry. Compared to controls, Lunge, 10-Meter
      Walking, and 9-Hole-Peg tests were impaired. Their CMT neuropathy score and
      functional disability scale showed that patients exhibited mild phenotype and at
      most slight walking difficulty. Electrophysiology revealed marked nerve
      conduction slowing and variable compound muscle action potential amplitude
      reduction. On lower-limb muscle MRI, there was distally accentuated fatty
      infiltration accompanied by edema in calf muscles. All these clinico
      electrophysiological and imaging findings remained almost unaltered during
      monitoring. Using multivariate analysis, no significant predictors of progression
      associated to the disease were obtained. We conclude that in the 2-year period of
      study, CMT1A patients showed mild progression with good concordance between
      clinico-electrophysiological and imaging findings.

PMID- 24449068
TI  - A leadership perspective : one year after becoming chair of a department.

PMID- 24449069
TI  - Characterization of psychiatry residency training programs.
AB  - Psychiatry residency training programs were characterized on four dimensions in a
      pilot study of seven West Coast schools. Residents and faculty rated their
      programs on academic versus clinical, community-based versus institution-based,
      private versus public practice, and biological versus psychological orientation.
      Faculty and residents from the same schools differed only on the academic
      clinical dimension. Significant differences existed between schools on each axis.
      Variation in ratings on the biological-psychological axis suggests that claims to
      a "biopsychosocial" orientation may be too broad to be meaningful. This method of
      dimensional ratings appears appropriate for program assessment and deserves
      further development. 

PMID- 24449070
TI  - Professional interests among residency applicants in psychiatry : a pilot study
      of autobiographical statements.
AB  - Spontaneous declarations of field of interest by 150 applicants to the UCLA
      Neuropsychiatric Institute-West Los Angeles V.A. Medical Center psychiatric
      residency program in 1986 were examined. In essays written as part of the
      National Resident Matching Program, many applicants expressed several areas of
      interest. About one-third of applicants expressed an interest in research, and
      about one-quarter expressed interests in teaching, psychotherapy, biological
      psychiatry, or child psychiatry. Between 5% and 9% expressed interest in
      community psychiatry, adolescent psychiatry, psychoanalysis, geriatric
      psychiatry, and chemical dependency, and <5% expressed interest in cross
      cultural, emergency, legal, or administrative psychiatry. 

PMID- 24449071
TI  - Post-psychiatry residency career choice : current trends.
AB  - Of 203 psychiatry residency directors surveyed in 1988 about the career choices
      of graduates, 97 (48%) usable responses represented 1,403 residents. Results were
      compared to previous surveys (1968-1972 and 1978-1979). The prior increase in
      post-residency fellowships (from 4% in 1968-1972 to 17% in 1978-1979) has leveled
      off (16.4% in 1988). Fewer residents chose academic psychiatry (9.7% in 1988
      versus 26% in 1978-1979); more are entering hospital-based psychiatry (22.8% in
      1988 versus 14% in 1978-1979). The proportions choosing private practice (28.7%)
      and community psychiatry (10%) are unchanged compared to 1978-1979. These
      findings reflect a departure from forecast expectations. 

PMID- 24449072
TI  - The role of current literature in psychiatric residency education.
AB  - Residents in 18 academic psychiatry residency programs were surveyed to assess
      the role of reading the current literature in residency education. Results are
      reported for 277 residents, a 39% response rate. Time spent on independent
      reading, use of the medical library, and use of computer searches of medical
      databases all reflected a relatively low level of autonomous educational
      activity. Reference to current literature was not an integral part of the
      educational climate of the residency programs surveyed. The implications of the
      findings, both for psychiatry residency education and for continuing medical
      education, are discussed. 

PMID- 24449073
TI  - A method of teaching and evaluating psychiatric case formulation.
AB  - Formulation is a poorly defined, core clinical skill in psychiatry. The authors
      present a method of teaching and evaluating biopsychosocial formulation of cases
      and introduce a reliable formulation marking scheme for scoring the
      comprehensiveness of a formulation. This method has been well received by four
      successive groups of residents, does not involve excessive reading or esoteric
      terminology, can be used within the time constraints of clinical practice, is
      flexible, and can be used for any psychiatric patient. 

PMID- 24449074
TI  - Psychiatry clerkship sites : factors that make a difference in student
      performance.
AB  - Using correlation ratios and analysis of variance, several potential variability
      factors in student clerkship performance were examined. Comparisons are made
      between clerkship clinical sites for scores on written work, clinical work, and
      examination scores, and for factors such as the amount of patient and faculty
      contact. A small amount of grade variance is due to clerkship site. Correlations
      between scores on clinical skills and examination scores were low, consistent
      with the idea that grades of clinical performance and performance on examinations
      measure different dimensions of student ability. The relevance for clerkship
      planning and grading equity is discussed. 

PMID- 24449075
TI  - 5-ALA complete resections go beyond MR contrast enhancement: shift corrected
      volumetric analysis of the extent of resection in surgery for glioblastoma.
AB  - BACKGROUND: The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is
      increasingly used to improve visualization of tumor tissue and thereby to
      increase the rate of patients with gross total resections. In this study, we
      measured the resection volumes in patients who underwent 5-ALA-guided surgery for
      non-eloquent glioblastoma and compared them with the preoperative tumor volume.
      METHODS: We selected 13 patients who had received a complete resection according
      to intraoperative 5-ALA induced fluorescence and CRET according to post-operative
      T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue,
      post-operative resection cavity and resected tissue were determined through shift
      corrected volumetric analysis. RESULTS: The mean resection cavity (29 cm(3)) was
      marginally smaller than the pre-operative contrast-enhancing tumor (39 cm(3), p =
      0.32). However, the mean overall resection volume (84 cm(3)) was significantly
      larger than the pre-operative contrast-enhancing tumor (39 cm(3), p = 0.0087).
      This yields a mean volume of resected 5-ALA positive, but radiological non
      enhancing tissue of 45 cm(3). The mean calculated rim of resected tissue
      surpassed pre-operative tumor diameter by 6 mm (range 0-10 mm). CONCLUSIONS:
      Results of the current study imply that (i) the resection cavity underestimates
      the volume of resected tissue and (ii) 5-ALA complete resections go significantly
      beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI,
      indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA
      may thus enable extension of coalescent tumor resection beyond radiologically
      evident tumor. The impact of this more extended resection method on time to
      progression and overall survival has not been determined, and potentially puts
      adjacent and functionally intact tissue at risk.

PMID- 24449076
TI  - In situ floating hydrogel for intravesical delivery of adriamycin without
      blocking urinary tract.
AB  - Drug solution is commonly used in conventional intravesical instillation.
      However, most of them would be easily eliminated by voiding, which significantly
      limit their efficacy. Recent advances in intravesical drug delivery are to use
      hydrogels as drug reservoir to extend the drug residence time in bladder.
      However, because of the high viscosity of hydrogel, urinary obstruction is
      usually existed during the intravesical instillation. To overcome these, we
      developed a floating hydrogel for the delivery of Adriamycin (ADR). The floating
      hydrogel was made of ADR, thermosensitive polymer (Poloxamer 407) and NaHCO3,
      which was liquid at low temperature, whereas formed gel at high temperature. In
      the presence of H+, NaHCO3 decomposed and produced CO2 that attached on the
      surface of hydrogel and helped the hydrogel float on the urine. Hence, the
      urinary tract will not be blocked. Meanwhile, the encapsulated ADR released in a
      controlled manner. These results suggest that the floating gel may have promising
      applications in intravesical therapy for bladder cancer.

PMID- 24449078
TI  - Association of interleukin-10 gene promoter polymorphisms with susceptibility to
      acute pyelonephritis in children.
AB  - Interleukin-10 (IL-10) is a potent inhibitor of leukocyte chemotaxis, bacterial
      killing in phagocytes and synthesis of pro-inflammatory cytokines and chemokines,
      and recent studies have suggested an important role for this immunoregulatory
      cytokine in the pathogenesis of urinary tract infections (UTIs). Therefore, the
      gene encoding IL-10 (IL10) is an attractive candidate for association studies
      attempting to identify susceptibility genes conferring risk of UTIs. In this case
      control study, we aimed to investigate the association of single nucleotide
      polymorphisms (SNPs) in the promoter region of IL10 with acute pyelonephritis in
      the Slovak population. Polymerase chain reaction with sequence-specific primers
      was used to analyse IL10 -1082A/G (rs1800896), -819C/T (rs1800871) and -592C/A
      (rs1800872) SNPs in 147 children with acute pyelonephritis and 215 healthy
      controls. Comparison of patients with healthy controls using the logistic
      regression analysis revealed significantly increased risk of developing recurrent
      attacks of acute pyelonephritis for -1082 G allele in a dominant genetic model GG
      (GG + AG vs. AA, P = 0.019, odds ratio (OR) = 2.26). A similar tendency was also
      found when the recurrent acute pyelonephritis subgroup was compared to episodic
      pyelonephritis cases (GG + AG vs. AA, P = 0.009, OR = 3.38). In conclusion, our
      results suggest that IL10 -1082 A/G SNP is a susceptibility factor for
      development of recurrent attacks of acute pyelonephritis.

PMID- 24449079
TI  - [Renaissance of pedicled flaps in oral and maxillofacial surgery].
AB  - A retrospective analysis in the period 2007 to 2011 included 71 surgically
      treated patients for carcinoma of the head and neck region and subsequent
      reconstruction with 36 pedicled distant flaps and 47 free flaps. Patient specific
      parameters of data collection with SPSS 17.0 were age and sex distribution, TNM
      stage and treatment. The specific type of flap reconstruction, duration of
      surgery, complications, intensive care and inpatient treatment were recorded. The
      results showed that the healing process was uneventful in 26 (72.2 %) pedicled
      flaps, 14 (38.9 %) pedicled flaps were transplanted in a preoperatively
      irradiated area of the head and neck region and in 86.0 % with a positive healing
      process. Tumor stage, general physical condition of the patient and type of
      therapy are the key parameters for the choice of reconstruction.

PMID- 24449080
TI  - [Gunshot wounds: should projectiles and fragments always be removed?].
AB  - BACKGROUND: Projectiles or metal fragments can remain lodged in the body of
      victims of gunshot injuries. This also applies to projectiles which do not tend
      to deform or fragment on impact. When a projectile fragments on penetration,
      jacket or lead core particles are likely to remain lodged in the affected region
      even if the projectile has exited the body. AIM OF THE STUDY: A frequently asked
      question in the surgical management of such injuries is whether there are medical
      indications for the surgical removal of projectiles or fragments. MATERIAL AND
      METHODS: This article presents some typical cases of patients who have received
      treatment at our institution and reviews the pertinent literature to show general
      recommendations in special cases concerning the removal of projectiles or
      fragments and when additional surgical trauma is justified. Parameters for
      decision making are presented in an algorithm. RESULTS: From our own patients, 5
      with remaining fragments in the soft tissue were invited for a clinical follow
      up. Serum probes and 24 h urine output was analysed for serum lead levels and
      urinary aminolevulinic acid levels. 74 months (max. 128 - min. 42 months) after
      injury we documented not elevated serum lead levels of 8.25 MUg/ml and urinary
      aminolevulinic acid levels of 4.8 mg/24 h. DISCUSSION: When lead-containing
      projectiles or fragments remain lodged in the body, monitoring is required and
      includes the measurement of serum lead levels and urinary aminolevulinic acid
      levels. The most important clinical symptoms of lead poisoning are
      gastrointestinal and neurological in nature. The treatment of choice for lead
      poisoning is the administration of chelating agents and removal of the lead
      source by surgical intervention.

PMID- 24449081
TI  - [Modern treatment of an appendiceal mass].
AB  - BACKGROUND: The recommendations for the treatment of an appendiceal mass are
      still controversial. The need for staged appendectomy is still under discussion.
      PATIENTS AND METHODS: In a retrospective study all patients with the diagnosis
      appendiceal mass (ICD 10 K35.32) treated in the surgical clinic of the University
      Clinic in Greifswald between June 1999 and June 2011 were analyzed. RESULTS: A
      total of 38 patients were included in the study whereby 17 patients (9 male and 8
      female) were treated with drainage and antibiotics (group A) and 21 (14 male and
      7 female) were treated by immediate surgery (group B). Nonsurgical therapy with
      drainage of the abscess was found to be efficient. Immediate surgical treatment
      was also effective and should be performed when signs of peritonitis exist.
      Interval appendectomy is not indicated.

PMID- 24449082
TI  - [Screening of carotid arteries before surgery: when does preoperative duplex
      ultrasound make sense?].
AB  - Carotid artery stenosis is a marker for generalized atherosclerosis with high
      cerebrovascular and cardiovascular morbidity and mortality rates. There is an
      estimated increase in prevalence of moderate stenosis for older age and male sex.
      Asymptomatic carotid artery stenosis is a risk factor for perioperative
      neurological events during general surgery. Planning of effective preoperative
      screening of populations at risk for asymptomatic carotid artery stenosis is best
      evaluated for cardiac surgery. General screening is not recommended; however,
      preoperative screening for asymptomatic carotid artery stenosis should be
      performed in high-risk patients with options for surgical or interventional
      treatment. These are patients with clinical signs of peripheral arterial disease
      and patients over 65 years old with at least one of the risk factors coronary
      artery disease, smoking and hypercholesterinemia. Preoperative screening in
      patients with carotid bruits may also be useful. Preoperative carotid artery
      screening may be beneficial in detecting occult carotid artery stenosis and
      thereby reducing perioperative neurological events. 

PMID- 24449083
TI  - [Incidence of non-metastatic liver lesions in tumor patients: consequences for
      chemotherapy and local ablative procedures].
AB  - INTRODUCTION: Even in patients with a history of solid malignant tumors,
      especially of gastrointestinal origin, newly diagnosed solid liver lesions do not
      necessarily correspond to metastases of the respective primary tumor. A reliable
      diagnosis can only be made by definitive histological examination. MATERIAL AND
      METHODS: Data of all patients who underwent liver resection under the
      preoperative diagnosis of liver metastases between 1997 and 2011 and for whom
      liver specimens were examined histologically, were extracted from the
      prospectively maintained cancer registry. RESULTS: An unexpected histological
      result occurred in 47 out of 770 patients (6.1 %). Primary tumors in these
      patients included renal cell (n=12), colorectal (n=11), breast (n=8), gastric
      (n=4), pancreatic (n=3), skin (n=3) and other cancers (n=6). Liver lesions were
      diagnosed synchronously in 15 cases or metachronously after a median of 17 months
      following primary therapy in 32 patients. Histology revealed a benign tumor in 38
      cases (81 %) as well as 6 cases of HCC, 2 cases of CCC and in 1 case metastasis
      of a previously unknown colorectal cancer in a patient with known esophageal
      carcinoma. Suspicion of metastatic disease was based on four different imaging
      modalities in two cases and on three different imaging modalities in nine cases.
      Either computed tomography (CT) or magnetic resonance imaging (MRI) was combined
      with ultrasound in another 23 patients and with positron emission tomography
      (PET) CT in 6 more cases. In two patients CT plus MRI and CT only, respectively,
      was performed. In the remaining three patients, suspicion of metastases occurred
      intraoperatively after macroscopic examination of the liver. Preoperative
      percutaneous biopsy was attempted in four patients with indeterminate results.
      CONCLUSION: Even with modern diagnostics the risk of treating a benign or other
      form of malignant tumor with neoadjuvant or palliative chemotherapy persists. The
      same holds true for local ablative procedures. Prior to local ablation or
      definitive palliative chemotherapy histological confirmation of metastases should
      be attempted.

PMID- 24449084
TI  - Effect of Abnormal Savda Munziq on hypertrophic scar formation in a rabbit ear
      model.
AB  - OBJECTIVE: To investigate whether administrating Abnormal Savda Munziq (ASMq), a
      traditional Uighur herbal preparation used for the prevention or treatment of
      diseases, affects hypertrophic scar (HTS) formation by using an established
      rabbit ear model. METHODS: The HTS rabbit model was created by circular
      fullthickness skin excisions on both ears of rabbits. Twenty rabbits were
      randomized into four groups, with 5 rabbits and 60 wounds in each group. Group A
      was the control group, treated with normal saline daily. Groups B, C, and D were
      the treatment groups at three different doses of ASMq (400, 800, and 1200 mg/kg
      body weight, respectively, daily, by gastrogavage). Twenty wounds were randomly
      chosen from each group on the 40th day after treatment and specimen were
      examined. Scar elevation index (SEI) was analyzed with histological assessment,
      and ultrastructure analysis was analyzed with a transmission electron microscopy.
      RESULTS: Groups B, C, and D demonstrated significant reductions in SEI as
      compared with the control group at 35.9% (P=0.0212), 48.2% (P=0.0108), and 52.7%
      (P=0.0103), respectively in a dose-response manner. SEI was lowered in Group D
      compared with Group B with a significant difference (P=0.015). However, there
      were no significant differences between Groups B and C, or between Groups C and
      D. Histological analysis showed that highdose ASMq (1200 mg/kg) could enhance the
      softening of HTS of rabbit ears and increase the compliance as shown in general.
      Ultrastructure analysis showed that with increased ASMq dose, the fibroblasts,
      pro-collagen, collagen, endoplasmic reticulum and ribosomes were reduced
      gradually. CONCLUSIONS: Orally administered ASMq significantly reduces the
      severity of HTS in the rabbit ear model. The findings of this study may have
      clinical implications on the management of human HTS.

PMID- 24449085
TI  - Psychological treatments for depression and anxiety in dementia and mild
      cognitive impairment.
AB  - BACKGROUND: Experiencing anxiety and depression is very common in people with
      dementia and mild cognitive impairment (MCI). Psychological interventions have
      been suggested as a potential treatment for these populations. Current research
      suggests that people with dementia and MCI have limited opportunities for
      psychological treatments aimed at improving their well-being. A systematic review
      of the evidence on their effectiveness is likely to be useful in terms of
      improving outcomes for patients and for future recommendations for practice.
      OBJECTIVES: The main objective of this review was to assess the effectiveness of
      psychological interventions in reducing anxiety and depression in people with
      dementia or mild cognitive impairment (MCI). SEARCH METHODS: We searched the
      Cochrane Dementia and Cognitive Improvement Group Specialized Register and
      additional sources for both published and unpublished data. SELECTION CRITERIA:
      We included randomised controlled trials (RCTs) comparing a psychological
      intervention with usual care or a placebo intervention (social contact control)
      in people with dementia or MCI. DATA COLLECTION AND ANALYSIS: Two review authors
      worked independently to select trials, extract data and assess studies for risk
      of bias, using a data extraction form. We contacted authors when further
      information was not available from the published articles. MAIN RESULTS: Six RCTs
      involving 439 participants with dementia were included in the review, but no
      studies of participants with MCI were identified. The studies included people
      with dementia living in the community or in nursing home care and were carried
      out in several countries. Only one of the studies was classified as low risk of
      bias. Five studies were at unclear or high risk of bias due to uncertainties
      around randomisation, blinding and selective reporting of results. The studies
      used the different psychological approaches of cognitive behavioural therapy
      (CBT), interpersonal therapy and counselling. Two studies were of multimodal
      interventions including a specific psychological therapy. The comparison groups
      received either usual care, attention-control educational programs, diagnostic
      feedback or services slightly above usual care.Meta-analysis showed a positive
      effect of psychological treatments on depression (6 trials, 439 participants,
      standardised mean difference (SMD) -0.22; 95% confidence interval (CI) -0.41 to 
      0.03, moderate quality evidence) and on clinician-rated anxiety (2 trials, 65
      participants, mean difference (MD) -4.57; 95% CI -7.81 to -1.32, low quality
      evidence), but not on self-rated anxiety (2 trials, SMD 0.05; 95% CI -0.44 to
      0.54) or carer-rated anxiety (1 trial, MD -2.40; 95% CI -4.96 to 0.16). Results
      were compatible with both benefit and harm on the secondary outcomes of patient
      quality of life, activities of daily living (ADLs), neuropsychiatric symptoms and
      cognition, or on carers' self-rated depressive symptoms, but most of the studies
      did not measure these outcomes. There were no reports of adverse events. AUTHORS'
      CONCLUSIONS: We found evidence that psychological interventions added to usual
      care can reduce symptoms of depression and clinician-rated anxiety for people
      with dementia. We conclude that psychological interventions have the potential to
      improve patient well-being. Further high quality studies are needed to
      investigate which treatments are most effective and to evaluate the effect of
      psychological interventions in people with MCI.

PMID- 24449086
TI  - Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva
      heterotopic endochondral ossification.
AB  - Bone morphogenetic protein (BMP) signaling is a critical regulator of cartilage
      differentiation and endochondral ossification. Gain-of-function mutations in
      ALK2, a type I BMP receptor, cause the debilitating disorder fibrodysplasia
      ossificans progressiva (FOP) and result in progressive heterotopic
      (extraskeletal) endochondral ossification within soft connective tissues. Here,
      we used murine mesenchymal progenitor cells to investigate the contribution of
      Alk2 during chondrogenic differentiation and heterotopic endochondral
      ossification (HEO). Alk2(R206H/+) (gain-of-function), Alk2(CKO) (loss-of
      function), and wild-type mouse embryonic fibroblasts were evaluated for
      chondrogenic potential. Chondrogenic differentiation was accelerated in
      Alk2(R206H/+) cells, due in part to enhanced sensitivity to BMP ligand. In vivo,
      Alk2(R206H/+) cells initiated robust HEO and recruited wild-type cell
      contribution. Despite expression of other type I BMP receptors (Alk3 and Alk6),
      chondrogenesis of Alk2(CKO) cells was severely impaired by absence of Alk2 during
      early differentiation. Alk2 is therefore a direct regulator of cartilage
      formation and mediates chondrogenic commitment of progenitor cells. These data
      establish that at least one effect of ALK2 gain-of-function mutations in FOP
      patients is enhanced chondrogenic differentiation which supports formation of
      heterotopic endochondral bone. This establishes ALK2 as a plausible therapeutic
      target during early chondrogenic stages of lesion formation for preventing
      heterotopic bone formation in FOP and other conditions.

PMID- 24449089
TI  - Impaired pentagon drawing is an early predictor of cognitive decline in
      Parkinson's disease.

PMID- 24449091
TI  - Inflammatory lymphangiogenesis: cellular mediators and functional implications.
AB  - In adult mammals, lymphatic vessels have been shown to respond to their
      environment by undergoing lymphangiogenesis, the formation of new lymphatic
      vessels from preexisting ones. Accumulating experimental and preclinical studies
      demonstrate that lymphangiogenesis is associated with many inflammatory diseases
      and may represent an attractive therapeutic target for inflammatory diseases.
      Thus, a better understanding of how lymphangiogenesis is regulated and
      contribution to inflammation is critical and may benefit clinical research
      targeting chronic inflammatory diseases. This review discusses the biological
      functions of lymphangiogenesis during inflammation and our current understanding
      of the key cellular players that can either support or limit lymphangiogenesis.
      Current data suggest that the context and time frame in which lymphangiogenesis
      occurs will determine its impact on the course of inflammation. 

PMID- 24449090
TI  - Inflammation-induced lymphangiogenesis and lymphatic dysfunction.
AB  - The lymphatic system is intimately linked to tissue fluid homeostasis and immune
      cell trafficking. These functions are paramount in the establishment and
      development of an inflammatory response. In the past decade, an increasing number
      of reports has revealed that marked changes, such as lymphangiogenesis and
      lymphatic contractile dysfunction occur in both vascular and nodal parts of the
      lymphatic system during inflammation, as well as other disease processes. This
      review provides a critical update on the role of the lymphatic system in disease
      process such as chronic inflammation and cancer and examines the changes in
      lymphatic functions the diseases cause and the influence these changes have on
      the progression of the diseases. 

PMID- 24449092
TI  - Predicting non-adherence in patients with familial hypercholesterolemia.
AB  - PURPOSE: Familial hypercholesterolemia (FH) is an autosomal dominant disorder
      associated with a high risk of premature coronary heart disease (CHD). CHD
      prevention consists of lifestyle changes combined with lifelong statin treatment.
      Good adherence to statins reduces the risk of events substantially. This study
      was designed to identify determinants of non-adherence and to develop a model
      predicting non-adherence. METHODS: A single centre survey included all
      consecutive heterozygous FH patients above age 18 years, who were treated by a
      specialized team in the outpatient clinic of a university hospital in The
      Netherlands between 2008 and 2009. In addition to clinical data, patients
      completed a questionnaire concerning medication adherence. RESULTS: We analyzed
      321 patients (169 women) with a statin prescription whose mean age was 46 +/- 14
      years (+/- S.D.), and 13 % of the patients had CHD. The untreated mean total
      cholesterol was 10 +/- 2.3 mmol/l. On average, patients were ten years on
      cholesterol-lowering therapy (range 1-29 years). Adherence was reported by 89 %
      of the patients (> 90 % adherence). Non-adherence was associated with younger age
      (OR = 10.64, 95 % CI 2.86-39.68), high total cholesterol level during
      prescription (OR = 4.29, 95 % CI 1.86-9.89) and a relatively low untreated total
      cholesterol level (OR = 3.94 95 % CI 1.39-11.14). A prediction model based on
      these three determinants had a c-index of 0.78 and a calibration with P = 0.88.
      CONCLUSION: Based on three independent determinants, a prediction model is
      developed to identify non-adherent FH patients. This model needs to be tested in
      future prospective research. It might be a first step in improving statin
      adherence in this extremely high risk group.

PMID- 24449093
TI  - Ecotoxicity of single-wall carbon nanotubes to freshwater snail Lymnaea luteola
      L.: Impacts on oxidative stress and genotoxicity.
AB  - Mammalian studies have raised concerns about the toxicity of carbon nanotubes,
      but there is very limited data on ecogenotoxicity to aquatic organisms. The aim
      of this study was to determine eco-geno toxic effects of single walled carbon
      nanotubes (SWCNTs) in fresh water snail, Lymnea luteola (L. luteola). A static
      test system was used to expose L. luteola to a freshwater control, 0.05, 0.15,
      0.30, 0.46 mg/L SWCNTs for up to 4 days. SWCNTs changed a significant reduction
      in glutathione, glutathione-S-transferase, and glutathione peroxidase with in
      hepatopancreas of L. luteola. Lipid peroxidation (LPO) and catalase showed dose-
      and time-dependent and statistically significant increase in hepatopancreas
      during SWCNTs exposure compared with control. However, a significant (p < 0.01)
      induction in DNA damage was observed by the comet assay in hepatopancreas cells
      treated with SWCNTs. These results demonstrate that SWCNTs are ecogenotoxic to
      freshwater snail L. luteola. The oxidative stress and comet assay can
      successfully be used as sensitive tools of aquatic pollution biomonitoring.

PMID- 24449094
TI  - Direct catalytic trifluoromethylthiolation of boronic acids and alkynes employing
      electrophilic shelf-stable N-(trifluoromethylthio)phthalimide.
AB  - A new and safe method for the synthesis of N-(trifluoromethylthio)phthalimide, a
      convenient and shelf-stable reagent for the direct trifluoromethylthiolation, has
      been developed. N-(Trifluoromethylthio)phthalimide can be used as an
      electrophilic source of F3 CS(+) and reacts readily with boronic acids and
      alkynes under copper catalysis. The utility of CF3 S-containing molecules as
      biologically active agents, the mild reaction conditions employed, and the high
      tolerance of functional groups demonstrate the potential of this new methodology
      to be widely applied in organic synthesis as well as industrial pharmaceutical
      and agrochemical research and development. 

PMID- 24449095
TI  - Patient perspective on survivorship.

PMID- 24449096
TI  - Ethical considerations for the clinical oncologist in an era of oncology drug
      shortages.
AB  - Shortages of injectable drugs affect many cancer patients and providers in the
      U.S. today. Scholars and policymakers have recently begun to devote increased
      attention to these issues, but only a few tangible resources exist to guide
      clinical oncologists in developing strategies for dealing with drug shortages on
      a recurring basis. This article discusses existing information from the scholarly
      literature, policy analyses, and other relevant sources and seeks to provide
      practical ethical guidance to the broad audience of oncology professionals who
      are increasingly confronted with such cases in their practice. We begin by
      providing a brief overview of the history, causes, and regulatory context of
      oncology drug shortages in the U.S., followed by a discussion of ethical
      frameworks that have been proposed in this setting. We conclude with practical
      recommendations for ethical professional behavior in these increasingly common
      and challenging situations. 

PMID- 24449097
TI  - Well-Being and Personal Growth in Mothers of Full-Term and Pre-Term Singletons
      and Twins.
AB  - The present study examined well-being and personal growth in mothers (n = 414) 1
      year after childbirth. We examined the contribution of the event characteristics
      (birth of singletons or twins, full- or pre-term babies, first or non-first
      child, spontaneous pregnancy or fertility treatments and infant temperament),
      internal resources (attachment anxiety and avoidance) and external resources
      (marital quality and maternal grandmother's support). Regressions indicated that
      having a first child, child's easier temperament, lower attachment anxiety and
      avoidance, grandmother's emotional support and some aspects of the spousal
      relationships contributed to well-being. Personal growth was found to be related
      to the birth of a pre-term baby or babies, positively associated with maternal
      grandmother's support, and the marital quality of parenthood, and negatively with
      mothers' education. Beyond the findings that well-being and personal growth are
      related to the availability of certain resources, the current study demonstrates
      that the two outcomes are separate phenomena that reveal different patterns of
      associations with other variables. Several explanations for the findings are
      proposed, and practical implications are discussed.

PMID- 24449099
TI  - Con: Thresholds to define chronic kidney disease should not be age dependent.

PMID- 24449100
TI  - Pro: Thresholds to define chronic kidney disease should not be age-dependent.

PMID- 24449101
TI  - Glomerular filtration rate estimation using cystatin C alone or combined with
      creatinine as a confirmatory test.
AB  - BACKGROUND: Glomerular filtration rate (GFR) estimating equations using the
      combination of creatinine and cystatin C (eGFRcr-cys) are more accurate than
      equations using either alone (eGFRcr or eGFRcys). New guidelines suggest
      measuring cystatin C as a confirmatory test when eGFRcr may be inaccurate, but do
      not specify demographic or clinical conditions in which eGFRcys or eGFRcr-cys are
      more accurate than eGFRcr nor which estimate to use in such circumstances.
      METHODS: We compared the performance of the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equations in 1119 subjects in the CKD-EPI cystatin C
      external validation dataset. Subgroups were defined by eGFRcr, age, sex, diabetes
      status and body mass index (BMI). The reference test was GFR measured using
      urinary or plasma clearance of exogenous filtration markers. Cystatin C and
      creatinine assays were traceable to primary reference materials. Accuracy was
      defined as the absolute difference in eGFR compared with mGFR. RESULTS: The mean
      mGFR was 70 +/- 41 (SD) mL/min/1.73 m(2). eGFRcys was more accurate than eGFRcr
      at lower BMI and less accurate at higher BMI, especially at higher levels of
      eGFRcr. There were small differences in accuracy in people according to the
      diabetes status. eGFRcr-cys was as accurate or more accurate than eGFRcr or
      eGFRcys in these and all other subgroups. CONCLUSIONS: eGFRcr-cys, but not
      eGFRcys, is more accurate than eGFRcr in most subgroups we studied, suggesting
      preferential use of eGFRcr-cys when serum cystatin C is measured as a
      confirmatory test to obtain more accurate eGFR. Further studies are necessary to
      evaluate diagnostic strategies for using eGFRcys and eGFRcr-cys.

PMID- 24449102
TI  - New renal guidelines; is more better?

PMID- 24449103
TI  - Podocytopenia, parietal epithelial cells and glomerulosclerosis.

PMID- 24449104
TI  - High-performance information search filters for acute kidney injury content in
      PubMed, Ovid Medline and Embase.
AB  - BACKGROUND: We frequently fail to identify articles relevant to the subject of
      acute kidney injury (AKI) when searching the large bibliographic databases such
      as PubMed, Ovid Medline or Embase. To address this issue, we used computer
      automation to create information search filters to better identify articles
      relevant to AKI in these databases. METHODS: We first manually reviewed a sample
      of 22 992 full-text articles and used prespecified criteria to determine whether
      each article contained AKI content or not. In the development phase (two-thirds
      of the sample), we developed and tested the performance of >1.3-million unique
      filters. Filters with high sensitivity and high specificity for the
      identification of AKI articles were then retested in the validation phase
      (remaining third of the sample). RESULTS: We succeeded in developing and
      validating high-performance AKI search filters for each bibliographic database
      with sensitivities and specificities in excess of 90%. Filters optimized for
      sensitivity reached at least 97.2% sensitivity, and filters optimized for
      specificity reached at least 99.5% specificity. The filters were complex; for
      example one PubMed filter included >140 terms used in combination, including
      'acute kidney injury', 'tubular necrosis', 'azotemia' and 'ischemic injury'. In
      proof-of-concept searches, physicians found more articles relevant to topics in
      AKI with the use of the filters. CONCLUSIONS: PubMed, Ovid Medline and Embase can
      be filtered for articles relevant to AKI in a reliable manner. These high
      performance information filters are now available online and can be used to
      better identify AKI content in large bibliographic databases.

PMID- 24449105
TI  - Randomized controlled trial to evaluate the impact of aerobic exercise on
      visceral fat in overweight chronic kidney disease patients.
AB  - BACKGROUND: The prevalence of obesity has markedly increased in patients with
      chronic kidney disease (CKD). Studies on the impact of exercise focusing on obese
      CKD patients are scarce. Therefore, we aimed to investigate the effect of aerobic
      exercise performed either in an exercise centre or at home on visceral fat in
      overweight non-dialysed CKD patients. METHODS: Twenty-seven sedentary men (52.1
      +/- 9.5 years, body mass index 30.4 +/- 3.8 kg/m(2), estimated glomerular
      filtration rate (eGFR) 27.5 +/- 11.6 mL/min) were randomly assigned to a centre
      based exercise group (n = 10), home-based exercise group (n = 8) or control group
      (n = 9). The aerobic training was prescribed according to ventilatory threshold
      and performed three times per week during 12 weeks. Body composition was assessed
      by dual energy X-ray absorptiometry (DEXA) and the distribution of abdominal fat
      by computed tomography. RESULTS: In the centre-based group, visceral fat and
      waist circumference decreased 6.4 +/- 6.4 mm (P < 0.01) and 2.0 +/- 2.3 cm (P =
      0.03) and leg lean mass increased 0.5 +/- 0.4 kg (P < 0.01). No significant
      changes were observed in the home-based group. Visceral fat increased 5.0 +/- 4.4
      mm in the control group (P = 0.01). In relation to the control, a group-by-time
      interaction was significant for visceral fat and waist circumference for both
      exercise groups and for leg lean mass for the centre-based group. Mean blood
      pressure decreased in both exercise groups (centre-based 13%, P < 0.01 and home
      based 10%, P = 0.03) and eGFR increased 3.6 +/- 4.6 mL/min (P = 0.03) in the
      centre-based group. These parameters remained unchanged in the control group.
      CONCLUSIONS: Centre-based aerobic exercise is an effective approach to reduce
      visceral fat besides promoting relevant clinical benefits in male overweight CKD
      patients.

PMID- 24449106
TI  - Widespread suppression of intragenic transcription initiation by H-NS.
AB  - Widespread intragenic transcription initiation has been observed in many species.
      Here we show that the Escherichia coli ehxCABD operon contains numerous
      intragenic promoters in both sense and antisense orientations. Transcription from
      these promoters is silenced by the histone-like nucleoid structuring (H-NS)
      protein. On a genome-wide scale, we show that 46% of H-NS-suppressed transcripts
      in E. coli are intragenic in origin. Furthermore, many intergenic promoters
      repressed by H-NS are for noncoding RNAs (ncRNAs). Thus, a major overlooked
      function of H-NS is to prevent transcription of spurious RNA. Our data provide a
      molecular description for the toxicity of horizontally acquired DNA and explain
      how this is counteracted by H-NS. 

PMID- 24449108
TI  - Maximizing integrated optical and electrical properties of a single ZnO nanowire
      through native interfacial doping.
AB  - A native interfacial doping layer introduced in core-shell type ZnO nano-wires by
      a simple vapor phase re-growth procedure endows the produced nano-wires with both
      excellent electrical and optical performances compared to conventional
      homogeneous ZnO nanowires. The unique Zn-rich interfacial structure in the core
      shell nanowires plays a crucial role in the outstanding performances. 

PMID- 24449107
TI  - Construction of synthetic nucleoli in human cells reveals how a major functional
      nuclear domain is formed and propagated through cell division.
AB  - Human cell nuclei are functionally organized into structurally stable yet dynamic
      bodies whose cell cycle inheritance is poorly understood. Here, we investigate
      the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key
      regulators of cellular growth. Nucleolar and cell cycles are intimately
      connected. Nucleoli disappear during mitosis, reforming around prominent
      uncharacterized chromosomal features, nucleolar organizer regions (NORs). By
      examining the effects of UBF depletion on both endogenous NORs and synthetic
      pseudo-NORs, we reveal its essential role in maintaining competency and
      establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo
      NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the
      de novo biogenesis of functional compartmentalized neonucleoli irrespective of
      their site of chromosomal integration. For the first time, we establish the
      sequence requirements for nucleolar biogenesis and provide proof that this is a
      staged process where UBF-dependent mitotic bookmarking precedes function
      dependent nucleolar assembly. 

PMID- 24449109
TI  - New sections.

PMID- 24449110
TI  - The psychotherapy curriculum in the age of biological psychiatry : mixing oil
      with water?
AB  - The field of psychiatry is characterized by tensions and philosophical
      differences. These tensions are described as a set of dilemmas facing the
      training director when designing the psychotherapy curriculum for residents. A
      solution to these dilemmas is presented. As a concrete example, the recently
      developed psychotherapy training program at the University of Washington in
      Seattle is described. 

PMID- 24449111
TI  - The role of medical school electives in the choice of child psychiatry as a
      subspecialty.
AB  - Part of child psychiatry's recruitment problem stems from defections among
      medical students who were planning careers in child psychiatry when they entered
      medical school The authors present data showing that between 1974 and 1984
      University of Maryland Medical School graduates specializing in psychiatry were
      more than twice as likely to enter fellowships in child and adolescent psychiatry
      if they were participants in the Combined Accelerated Program in Psychiatry
      (CAPP) as medical students. The CAPP, a 4-year medical school track that contains
      a strong child psychiatry component, appears to prevent the erosion of students'
      interest in child psychiatry. 

PMID- 24449112
TI  - Long-term Evaluation of a Psychiatry Clerkship.
AB  - For over 14 years, students completing a psychiatry clerkship were asked to rate
      their educational experience. Comparisons were made across clinical assignment,
      length of rotation (6 vs. 8 weeks), and teaching modes. Consultation and acute
      services were rated higher than open adult or child/adolescent services. General
      units were rated higher than specialty units. Ratings were higher for 8-week
      rotations, and case conferences were preferred to lecture formats. Ratings were
      not significantly correlated with National Board of Medical Examiners examination
      scores, which were higher during years with 8-week rotations and case
      conferences. There was a tendency for students on the consultation and acute
      services to enter psychiatry residencies at a higher rate. 

PMID- 24449113
TI  - A rating inventory for resident case presentations.
AB  - We devised a rating scale, the Resident Case Presentation Inventory (RCPI), to
      evaluate psychiatry residents' case presentations at our hospital's disposition
      conference. A review of 69 inpatient cases presented prior to discharge revealed
      that residents' greatest deficiencies were in the following two areas: 1) knowing
      indications for specific outpatient treatments and 2) coordinating input from
      various clinical disciplines, both inpatient and outpatient. The RCPI allows
      early identification of residents' educational needs and can give ongoing
      feedback on their progress. 

PMID- 24449114
TI  - Teaching psychiatric residents to teach.
AB  - Teaching other residents and medical students is one of the primary activities of
      psychiatric residents, yet most receive minimal or no formal training or
      supervision on how to teach. This report describes a Teaching Day Workshop,
      designed and implemented by residents at the Massachusetts General Hospital with
      the support of their faculty and an educational consultant, as one model to
      introduce the concepts and techniques of teaching to psychiatric residents. The
      participating residents were unanimous in their positive appraisal of the
      workshop, and they recommended that additional seminars on teaching be integrated
      into the residency's core curriculum. Ways that the Teaching Day Workshop can be
      adapted for use by other residency training programs are discussed. The authors
      believe that teaching residents to be better teachers can have an impact on
      recruitment of medical students into psychiatry and psychiatric residents into
      careers in academic psychiatry. 

PMID- 24449115
TI  - A residents' program for educating adolescents about mental health issues.
AB  - This paper describes a school-based program in which psychiatry residents educate
      adolescents about a variety of mental health topics. Adolescents responded
      positively to the program and were principally concerned about drugs, depression,
      suicide, and family problems. Residents also liked presenting in the schools.
      Participation in this program allowed residents to learn about agency
      consultation and secondary prevention. Possibilities for program expansion are
      discussed. 

PMID- 24449116
TI  - Private patients as an aid in medical student teaching.

PMID- 24449117
TI  - Didactic curriculum for postresidency fellowship training in psychiatrie
      research.

PMID- 24449118
TI  - Double supervision.

PMID- 24449119
TI  - In reply.

PMID- 24449120
TI  - Community psychiatry training.

PMID- 24449121
TI  - Validating MMI scores: are we measuring multiple attributes?
AB  - The multiple mini-interview (MMI) used in health professional schools' admission
      processes is reported to assess multiple non-cognitive constructs such as ethical
      reasoning, oral communication, or problem evaluation. Though validation studies
      have been performed with total MMI scores, there is a paucity of information
      regarding how well MMI scores differentiate the constructs being measured, the
      relationship between MMI scores (construct or total) and personality
      characteristics, and how well MMI scores (construct or total) predict future
      performance in practice. Results from these studies could assist with MMI station
      development, rater training, score interpretation, and resource allocation. The
      purpose of this study was to investigate the validity of MMI construct scores
      (oral communication and problem evaluation), and their relationship to
      personality measures (emotionality and extraversion) and specific scores from
      standardized clinical communications interviews (building the relationship and
      explaining and planning). Confirmatory factor analysis results support a two
      factor MMI model, however the correlation between these factors was .87. Oral
      communication MMI scores significantly correlated with extraversion (r c = .25, p
      < .05), but MMI scores were not related to emotionality. Scores for building a
      relationship were significantly related to MMI oral communication scores, (r c =
      .46, p < .001) and problem evaluation scores (r c = .43, p < .001); scores for
      explaining and planning were significantly related to MMI problem evaluation
      scores (r c = .36, p < .01). The results provide validity evidence for assessing
      multiple non-cognitive attributes during the MMI process and reinforce the
      importance of developing MMI stations and scoring rubrics for attributes
      identified as important for future success in school and practice.

PMID- 24449122
TI  - Effect of clinically discriminating, evidence-based checklist items on the
      reliability of scores from an Internal Medicine residency OSCE.
AB  - Objective structured clinical examinations (OSCEs) are used worldwide for
      summative examinations but often lack acceptable reliability. Research has shown
      that reliability of scores increases if OSCE checklists for medical students
      include only clinically relevant items. Also, checklists are often missing
      evidence-based items that high-achieving learners are more likely to use. The
      purpose of this study was to determine if limiting checklist items to clinically
      discriminating items and/or adding missing evidence-based items improved score
      reliability in an Internal Medicine residency OSCE. Six internists reviewed the
      traditional checklists of four OSCE stations classifying items as clinically
      discriminating or non-discriminating. Two independent reviewers augmented
      checklists with missing evidence-based items. We used generalizability theory to
      calculate overall reliability of faculty observer checklist scores from 45 first
      and second-year residents and predict how many 10-item stations would be required
      to reach a Phi coefficient of 0.8. Removing clinically non-discriminating items
      from the traditional checklist did not affect the number of stations (15)
      required to reach a Phi of 0.8 with 10 items. Focusing the checklist on only
      evidence-based clinically discriminating items increased test score reliability,
      needing 11 stations instead of 15 to reach 0.8; adding missing evidence-based
      clinically discriminating items to the traditional checklist modestly improved
      reliability (needing 14 instead of 15 stations). Checklists composed of evidence
      based clinically discriminating items improved the reliability of checklist
      scores and reduced the number of stations needed for acceptable reliability.
      Educators should give preference to evidence-based items over non-evidence-based
      items when developing OSCE checklists. 

PMID- 24449123
TI  - Learning with interactive computer graphics in the undergraduate neuroscience
      classroom.
AB  - Instruction of neuroanatomy depends on graphical representation and extended self
      study. As a consequence, computer-based learning environments that incorporate
      interactive graphics should facilitate instruction in this area. The present
      study evaluated such a system in the undergraduate neuroscience classroom. The
      system used the method of adaptive exploration, in which exploration in a high
      fidelity graphical environment is integrated with immediate testing and feedback
      in repeated cycles of learning. The results of this study were that students
      considered the graphical learning environment to be superior to typical classroom
      materials used for learning neuroanatomy. Students managed the frequency and
      duration of study, test, and feedback in an efficient and adaptive manner. For
      example, the number of tests taken before reaching a minimum test performance of
      90 % correct closely approximated the values seen in more regimented experimental
      studies. There was a wide range of student opinion regarding the choice between a
      simpler and a more graphically compelling program for learning sectional anatomy.
      Course outcomes were predicted by individual differences in the use of the
      software that reflected general work habits of the students, such as the amount
      of time committed to testing. The results of this introduction into the classroom
      are highly encouraging for development of computer-based instruction in
      biomedical disciplines.

PMID- 24449124
TI  - Utilizing codes of ethics in health professions education.
AB  - Codes of ethics abound in health care, the aims and purposes of which are
      multiple and varied, from operating as a decision making tool to acting as a
      standard of practice that can be operational in a legal context to providing a
      sense of elevated seriousness and professionalism within a field of practice.
      There is some doubt and controversy, however, regarding the value and use of
      these codes both in professional practice and in the education of healthcare
      professionals. I intend to review and analyze the various aims and purposes of
      ethics codes particularly within the study and practice of healthcare in light of
      various criticisms of codes of ethics. After weighing the strength and import of
      these criticisms, I plan to explore effective means for utilizing such codes as
      part of the ethics education of healthcare professionals. While noting
      significant limitations of this tool, both in practice and in education, I plan
      to demonstrate its potential usefulness as well, in both generating critical
      thinking within the study of ethics and as a guide for practice for the
      professional. 

PMID- 24449125
TI  - Estimation of post-test probabilities by residents: Bayesian reasoning versus
      heuristics?
AB  - Although the process of diagnosing invariably begins with a heuristic, we
      encourage our learners to support their diagnoses by analytical cognitive
      processes, such as Bayesian reasoning, in an attempt to mitigate the effects of
      heuristics on diagnosing. There are, however, limited data on the use +/- impact
      of Bayesian reasoning on the accuracy of disease probability estimates. In this
      study our objective was to explore whether Internal Medicine residents use a
      Bayesian process to estimate disease probabilities by comparing their disease
      probability estimates to literature-derived Bayesian post-test probabilities. We
      gave 35 Internal Medicine residents four clinical vignettes in the form of a
      referral letter and asked them to estimate the post-test probability of the
      target condition in each case. We then compared these to literature-derived
      probabilities. For each vignette the estimated probability was significantly
      different from the literature-derived probability. For the two cases with low
      literature-derived probability our participants significantly overestimated the
      probability of these target conditions being the correct diagnosis, whereas for
      the two cases with high literature-derived probability the estimated probability
      was significantly lower than the calculated value. Our results suggest that
      residents generate inaccurate post-test probability estimates. Possible
      explanations for this include ineffective application of Bayesian reasoning,
      attribute substitution whereby a complex cognitive task is replaced by an easier
      one (e.g., a heuristic), or systematic rater bias, such as central tendency bias.
      Further studies are needed to identify the reasons for inaccuracy of disease
      probability estimates and to explore ways of improving accuracy. 

PMID- 24449126
TI  - Interpretation of radiological images: towards a framework of knowledge and
      skills.
AB  - The knowledge and skills that are required for radiological image interpretation
      are not well documented, even though medical imaging is gaining importance. This
      study aims to develop a comprehensive framework of knowledge and skills, required
      for two-dimensional and multiplanar image interpretation in radiology. A mixed
      method study approach was applied. First, a literature search was performed to
      identify knowledge and skills that are important for image interpretation. Three
      databases, PubMed, PsycINFO and Embase, were searched for studies using synonyms
      of image interpretation skills or visual expertise combined with synonyms of
      radiology. Empirical or review studies concerning knowledge and skills for
      medical image interpretation were included and relevant knowledge and skill items
      were extracted. Second, a preliminary framework was built and discussed with nine
      selective experts in individual semi-structured interviews. The expert team
      consisted of four radiologists, one radiology resident, two education scientists,
      one cognitive psychologist and one neuropsychologist. The framework was optimised
      based on the experts comments. Finally, the framework was applied to empirical
      data, derived from verbal protocols of ten clerks interpreting two-dimensional
      and multiplanar radiological images. In consensus meetings adjustments were made
      to resolve discrepancies of the framework with the verbal protocol data. We
      designed a framework with three main components of image interpretation:
      perception, analysis and synthesis. The literature study provided four knowledge
      and twelve skill items. As a result of the expert interviews, one skill item was
      added and formulations of existing items were adjusted. The think-aloud
      experiment showed that all knowledge items and three of the skill items were
      applied within all three main components of the image interpretation process. The
      remaining framework items were apparent only within one of the main components.
      After combining two knowledge items, we finally identified three knowledge items
      and thirteen skills, essential for image interpretation by trainees. The
      framework can serve as a guideline for education and assessment of two- and three
      dimensional image interpretation. Further validation of the framework in larger
      study groups with different levels of expertise is needed. 

PMID- 24449127
TI  - Are we willing to change our impression of first impressions?

PMID- 24449128
TI  - Development and face validation of strategies for improving consultation skills.
AB  - While formative workplace based assessment can improve learners' skills, it often
      does not because the procedures used do not facilitate feedback which is
      sufficiently specific to scaffold improvement. Provision of pre-formulated
      strategies to address predicted learning needs has potential to improve the
      quality and automate the provision of written feedback. To systematically
      develop, validate and maximise the utility of a comprehensive list of strategies
      for improvement of consultation skills through a process involving both medical
      students and their clinical primary and secondary care tutors. Modified Delphi
      study with tutors, modified nominal group study with students with moderation of
      outputs by consensus round table discussion by the authors. 35 hospital and 21 GP
      tutors participated in the Delphi study and contributed 153 new or modified
      strategies. After review of these and the 205 original strategies, 265 strategies
      entered the nominal group study to which 46 year four and five students
      contributed, resulting in the final list of 249 validated strategies. We have
      developed a valid and comprehensive set of strategies which are considered useful
      by medical students. This list can be immediately applied by any school which
      uses the Calgary Cambridge Framework to inform the content of formative feedback
      on consultation skills. We consider that the list could also be mapped to
      alternative skills frameworks and so be utilised by schools which do not use the
      Calgary Cambridge Framework.

PMID- 24449129
TI  - Evolution of fetal ventricular dilatation in relation to severity at first
      presentation.
AB  - BACKGROUND: To assess the outcome of 360 cases of fetal ventriculomegaly in a
      tertiary referral center. METHODS: Cases of fetal ventriculomegaly between June
      1993 and December 2011 were identified from the departmental fetal database. The
      fetal medicine reports and obstetric notes were reviewed to ascertain the
      antenatal progression of the ventriculomegaly as well as the outcome of the
      pregnancy. Ventriculomegaly was defined by a lateral ventricular wall atrial
      measurement of greater than 10 mm. Cases were subdivided into mild (>10 to <12
      mm), moderate (>=12 to <15 mm), and severe (>=15 mm). Termination of pregnancy
      was offered in cases where there were associated anomalies, aneuploidy, or the
      ventriculomegaly progressed. RESULTS: Of the 360 cases, 189 were mild, 79 were
      moderate, and 92 were severe. Sixty-four percent of cases had associated
      anomalies. Forty-six percent of cases in the mild group and 26% in the moderate
      group resolved. Only one case in the severe group improved. The mean rate of
      progression in the mild group was 1.07 (SD 1.03) mm/week, whereas in the moderate
      group progression was at a mean rate of 1.41 (SD 0.77) mm/week. Progression of
      severe ventriculomegaly was significantly higher at a mean rate of 3.26 (SD 2.92)
      mm/week (p = 0.007). CONCLUSIONS: The majority of fetuses with mild
      ventriculomegaly normalized, whereas the majority of moderate cases remained
      stable. The rate of progression of ventriculomegaly increased with severity.
      Fetuses with ventriculomegaly should be offered serial scans to allow the
      progression of ventriculomegaly to be ascertained with the option of late
      termination of pregnancy.

PMID- 24449130
TI  - Semipolar polycyclic aromatic compounds: identification of 15 priority substances
      and the need for regulatory steps under REACH regulation.
AB  - Semipolar polycyclic aromatic compounds (sPACs) are frequently found in
      association with homocyclic polycyclic aromatic hydrocarbons (PAHs) in substances
      of unknown or variable composition, complex reaction products, or biological
      materials (UVCBs) from coal or crude oil and products derived thereof. However,
      major information deficiencies exist with regard to their prevalence and their
      toxicological and ecotoxicological potential, persistency, and bioaccumulation
      characteristics. Therefore, in this work, the environmental concern and relevance
      of sPACs was addressed in a general, stepwise approach. First, a large list of
      sPACs was collected and subsequently refined by assessing their persistence,
      bioaccumulation, and toxicity (PBT) properties by quantitative structure-activity
      relationship (QSAR) methods and their relevance by determining their respective
      frequency of occurrence. In this way, 15 priority sPACs were identified. These 15
      priority sPACs were further characterized in detail with respect to their
      ecotoxicological properties, environmental behavior, carcinogenicity, and
      genotoxicity attributes. All of these 15 substances were quantified in distillate
      or product samples. In the next step, some principles for nomination of indicator
      substances, indicative for the overall content of sPACs, are derived. Data gaps
      on ecotoxicological endpoints preclude final conclusions, but the respective
      necessary supplemental tests were identified. Five of the 15 sPACs were
      tentatively characterized as potential substances of very high concern (SVHC) for
      the environment. The overall results of this study also clearly show that
      regulatory risk management of homocyclic PAHs within the European Regulation on
      Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) does
      not address the environmental concern created by sPACs within UVCBs from coal or
      crude oil. The study proves the need for additional regulatory steps under REACH
      and suggests indicator substances for their enforcement.

PMID- 24449131
TI  - Control of protein particle formation during ultrafiltration/diafiltration
      through interfacial protection.
AB  - This study investigates the mechanism of protein particle formation during
      ultrafiltration/diafiltration (UF/DF), finding that agitation drives particle
      formation by promoting protein-interface adsorption and desorption. Low
      conductivity and the presence of surfactant reduced the level of particle
      formation in small-scale stirring studies, and the same trends were observed in
      pumping and UF/DF. Polysorbate 80 (PS80) and hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) reduced particle formation in UF/DF by factors of 15 and 4,
      respectively. Measurements of conformational stability, colloidal stability, and
      surface tension demonstrated that PS80 protects against particle formation by
      preventing protein-interface adsorption, low conductivity improves the colloidal
      stability of the protein, and the mechanism of action of HPbetaCD remains
      unclear. This work demonstrates that interfacial adsorption-desorption of the
      protein during UF/DF is the principal cause of particle formation, that the level
      of surfactant-free particle formation depends on the colloidal stability of the
      protein, and that the inclusion of surfactant greatly reduces in-process particle
      formation during UF/DF.

PMID- 24449132
TI  - Resveratrol Enhances Chemosensitivity in Mouse Melanoma Model Through Connexin 43
      Upregulation.
AB  - Although current studies indicate that resveratrol exhibits potential antitumor
      activities, the precise mechanisms of its beneficial effects combined with
      chemotherapy are not fully understood. This work is warranted to elucidate the
      underlying mechanism of antitumor effects by the combination therapy of
      resveratrol and cisplatin. The presence of functional gap junctions is highly
      relevant for the success of chemotherapy. Gap junctions mediate cell
      communication by allowing the passage of molecules from one cell to another.
      Connexin (Cx) 43 is ubiquitous and reduced in a variety of tumor cells. Cx43 may
      influence the response of tumor cells to treatments by facilitating the passage
      of antitumor drugs or death signals between neighboring tumor cells. Following
      resveratrol treatment, dose-dependent upregulation of Cx43 expressions was
      observed. In addition, gap junction intercellular communication was increased. To
      study the mechanism underlying these resveratrol-induced Cx43 expressions, we
      found that resveratrol induced a significant increase in mitogen-activated
      protein kinases (MAPK) signaling pathways. The MAPK inhibitors significantly
      reduced the expression of Cx43 protein after resveratrol treatment. Specific
      knockdown of Cx43 resulted in a reduction of cell death after resveratrol and
      cisplatin treatment. Our results suggest that treatment of resveratrol in tumor
      leads to increase Cx43 gap junction communication and enhances the combination of
      resveratrol and cisplatin therapeutic effects. (c) 2014 Wiley Periodicals, Inc.
      Environ Toxicol 30: 877-886, 2015. 

PMID- 24449133
TI  - An approach to the symbolic representation of brain arteriovenous malformations
      for management and treatment planning.
AB  - INTRODUCTION: There is currently no standardised approach to arteriovenous
      malformation (AVM) reporting. Existing AVM classification systems focuses on
      angioarchitectural features and omit haemodynamic, anatomical and topological
      parameters intuitively used by therapists. METHODS: We introduce a symbolic
      vocabulary to represent the state of an AVM of the brain at different stages of
      treatment. The vocabulary encompasses the main anatomic and haemodynamic features
      of interest in treatment planning and provides shorthand symbols to represent the
      interventions themselves in a schematic representation. RESULTS: The method was
      presented to 50 neuroradiologists from 14 countries during a workshop and graded
      7.34 +/- 1.92 out of ten for its usefulness as means of standardising and
      facilitating communication between clinicians and allowing comparisons between
      AVM cases. Feedback from the survey was used to revise the method and improve its
      completeness. For an AVM test case, participants were asked to produce a
      conventional written report and subsequently a diagrammatic report. The two
      required, on average, 6.19 +/- 2.05 and 5.09 +/- 3.01 min, respectively. Eighteen
      participants said that producing the diagram changed the way they thought about
      the AVM test case. CONCLUSION: Introduced into routine practice, the diagrams
      would represent a step towards a standardised approach to AVM reporting with
      consequent benefits for comparative analysis and communication as well as for
      identifying best treatment strategies.

PMID- 24449134
TI  - Use of time attenuation curves to determine steady-state characteristics before C
      arm CT measurement of cerebral blood volume.
AB  - INTRODUCTION: Cerebral blood volume (CBV) measurement by flat panel detector CT
      (FPCT) in the angiography suite seems to be a promising tool for patient
      management during endovascular therapies. A steady state of contrast agent
      distribution is mandatory during acquisition for accurate FPCT CBV assessment. To
      the best of our knowledge, this was the first time that steady-state parameters
      were studied in clinical practice. METHODS: Before the CBV study, test injections
      were performed and analyzed to determine a customized acquisition delay from
      injection for each patient. Injection protocol consisted in the administration of
      72 mL of contrast agent material at the injection rate of 4.0 mL/s followed by a
      saline flush bolus at the same injection rate. Peripheral or central venous
      accesses were used depending on their availability. Twenty-four patients were
      treated for different types of neurovascular diseases. Maximal attenuation,
      steady-state length, and steady-state delay from injection were derived from the
      test injections' time attenuation curves. RESULTS: With a 15 % threshold from
      maximum attenuation values, average steady-state duration was less than 10 s.
      Maximum average steady-state duration with minimal delay variation was obtained
      with central injection protocols. CONCLUSION: With clinically acceptable contrast
      agent volumes, steady state is a brief condition; thus, fast rotation speed
      acquisitions are needed. The use of central injections decreases the variability
      of steady-state's delay from injection. Further studies are needed to optimize
      and standardize injection protocols to allow a larger diffusion of the FPCT CBV
      measurement during endovascular treatments.

PMID- 24449135
TI  - Recovery, spirituality and psychotherapy.
AB  - This article concerns the relationship between addiction recovery, spirituality
      and psychotherapy. Since its founding, members of AA have been encouraged to
      pursue a spiritual life. They have also sought psychotherapy. A paradox obtains,
      because 51 % of therapists are atheists. Others have little awareness of the
      dynamics of the spiritual life. The developmental process of the spiritual life
      is discussed, and suggestions are made regarding how a therapist might be helpful
      in this process.

PMID- 24449136
TI  - Ocular diseases in metastatic cutaneous melanoma: review of 108 consecutive
      patients in two German tertiary centers.
AB  - PURPOSE: To analyze the incidence and spectrum of ocular disease in patients with
      metastatic cutaneous melanoma. METHODS: One hundred and eight consecutive
      patients with metastatic cutaneous melanoma were screened for ocular diseases
      using standardized eye examination, including measurement of visual acuity and
      intraocular pressure, slit-lamp examination, funduscopy in mydriasis, and
      spectral-domain optical coherence tomography (SDOCT) of the retina. Selected
      cases with atypical findings underwent electrophysiological studies. One patient
      was examined for hypercortisolism by a dexamethasone suppression test. RESULTS:
      Ocular diseases were found in 65 out of 108 patients (60 %) with metastatic
      cutaneous melanoma, significantly more often in older patients (p = 0.004).
      Cataract was present in 27 patients (25 %), pseudophakia in 22 patients (20 %),
      macular disease in 29 patients (28 %), diabetic retinopathy in ten patients (9
      %), hypertensive retinal disease in 14 patients (13 %), retinal venous and
      arterial occlusive disease in three patients (3 %), optic neuropathy in four
      patients (4 %), and uveitis in one patient (1 %). Eight patients (8 %) had
      choroidal or iridal nevi, one patient (1 %) choroidal hemangioma, and one patient
      (1 %) choroidal metastasis. No patient had periocular neoplastic lesions.
      Paraneoplastic retinopathy manifesting as acute exudative polymorphous
      vitelliform maculopathy (AEPVM)-like disease was diagnosed in two patients (2 %)
      with multifocal central serous chorioretinopathy and development of vitelliform
      or fibrin-like subretinal deposits in one patient. CONCLUSIONS: Patients with
      metastatic cutaneous melanoma reveal ocular diseases with a spectrum similar to
      the normal population of this age range. Very rarely, uveal metastasis as well as
      paraneoplastic retinopathy can occur.

PMID- 24449137
TI  - Explaining general anesthesia: a two-step hypothesis linking sleep circuits and
      the synaptic release machinery.
AB  - Several general anesthetics produce their sedative effect by activating
      endogenous sleep pathways. We propose that general anesthesia is a two-step
      process targeting sleep circuits at low doses, and synaptic release mechanisms
      across the entire brain at the higher doses required for surgery. Our hypothesis
      synthesizes data from a variety of model systems, some which require sleep (e.g.
      rodents and adult flies) and others that probably do not sleep (e.g. adult
      nematodes and cultured cell lines). Non-sleeping systems can be made insensitive
      (or hypersensitive) to some anesthetics by modifying a single pre-synaptic
      protein, syntaxin1A. This suggests that the synaptic release machinery, centered
      on the highly conserved SNARE complex, is an important target of general
      anesthetics in all animals. A careful consideration of SNARE architecture
      uncovers a potential mechanism for general anesthesia, which may be the primary
      target in animals that do not sleep, but a secondary target in animals that
      sleep. 

PMID- 24449138
TI  - [Genome-associated studies in chronic inflammatory dermatoses].
AB  - With a prevalence of 15 % in children and 5 % in adults and a lifetime prevalence
      of 3 %, atopic eczema and psoriasis vulgaris are the two most common chronic
      inflammatory forms of dermatosis. Both represent typical multifactorial diseases,
      the manifestation and progression of which are driven by the interaction of
      multiple genetic as well as environmental factors. The rapid technological
      development has led to deep insights into the genetic architecture of these
      diseases. In particular, genome-wide association studies have identified an
      impressive number of genetic risk factors and led to a better understanding of
      disease pathophysiology. Knowledge from genetic epidemiology is increasingly
      being translated in clinical applications, e.g. by the use of genetic markers for
      patient stratification and of involved pathways for development of innovative
      therapeutic approaches. New sequencing technologies and systems biology
      approaches will aid in gaining an even more comprehensive insight into the role
      of genetic information in the development of chronic inflammatory skin diseases. 

PMID- 24449139
TI  - [A 59-year-old patient with recurrent flushes and bland hepatic cyst].
AB  - A 59-year-old patient was admitted to hospital with recurrent flush symptoms and
      pathologically elevated 5-hydroxyindoleacetic acid (5-HIAA) levels in urine. A
      known cystic lesion of the liver which had been followed for years by ultrasound
      examinations and was regarded as a bland hepatic cyst was identified as a
      metastasis of a neuroendocrine neoplasm of the ileum. In two sequential surgical
      interventions the primary tumor with mesenteric lymph node metastases as well as
      the cystic liver metastasis could be resected. After surgical treatment an R1
      situation at the mesenteric site and suspicious para-aortic lymph nodes remained.
      The long established treatment of factor-V Leiden mutation by anticoagulation
      with phenprocoumon was supplemented by deep subcutaneous injection of lanreotide
      autogel every 4 weeks. Currently, there is no evidence for progressive disease
      and the patient is without clinical signs of a carcinoid syndrome. 

PMID- 24449140
TI  - Diffusion tensor imaging and magnetic resonance spectroscopy in traumatic brain
      injury: a review of recent literature.
AB  - Concussion is the most common form of traumatic brain injury (TBI), but diagnosis
      remains controversial because the brain appears quite normal in conventional
      computed tomography and magnetic resonance imaging (MRI). These conventional
      tools are not sensitive enough to detect diffuse traumatic axonal injury, and
      cannot depict aberrations in mild TBIs. Advanced MRI modalities including
      diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), make
      it possible to detect brain injuries in TBI. The purpose of this review is to
      provide the latest information regarding the visualization and quantification of
      important abnormalities in TBI and new insights into their clinical significance.
      Advanced imaging modalities allow the discovery of biomarkers of injury and the
      detection of changes in brain injury over time. Such tools will likely be used to
      evaluate treatment efficacy in research. Combining multiple imaging modalities
      would not only provide greater insight into the underlying physiological changes
      in TBI, but also improve diagnostic accuracy in predicting outcomes. In this
      review we present evidence of brain abnormalities in TBI based on investigations
      using MRI, including DTI and MRS. Our review provides a summary of some of the
      important studies published from 2002 to 2012 on the topic of MRI findings in
      head trauma. With the growing realization that even mild head injury can lead to
      neurocognitive deficits, medical imaging has assumed preeminence for detecting
      abnormalities associated with TBI. Advanced MRI modalities such as DTI and MRS
      have an important role in the diagnosis of lesions for TBI patients. 

PMID- 24449141
TI  - Diet of upper paleolithic modern humans: evidence from microwear texture
      analysis.
AB  - This article presents the results of the occlusal molar microwear texture
      analysis of 32 adult Upper Paleolithic modern humans from a total of 21 European
      sites dating to marine isotope stages 3 and 2. The occlusal molar microwear
      textures of these specimens were analyzed with the aim of examining the effects
      of the climatic, as well as the cultural, changes on the diets of the Upper
      Paleolithic modern humans. The results of this analysis do not reveal any
      environmentally driven dietary shifts for the Upper Paleolithic hominins
      indicating that the climatic and their associated paleoecological changes did not
      force these humans to significantly alter their diets in order to survive.
      However, the microwear texture analysis does detect culturally related changes in
      the Upper Paleolithic humans' diets. Specifically, significant differences in
      diet were found between the earlier Upper Paleolithic individuals, i.e., those
      belonging to the Aurignacian and Gravettian contexts, and the later Magdalenian
      ones, such that the diet of the latter group was more varied and included more
      abrasive foods compared with those of the former.

PMID- 24449142
TI  - Reduced cortical plasticity and GABAergic modulation in essential tremor.
AB  - Essential tremor (ET) is the most common movement disorder among adults.
      Cerebellar dysfunction is thought to be involved in the pathogenesis of ET;
      however, imaging, electrophysiological studies, and clinical observations have
      suggested that the cerebral cortex also may participate. We sought to investigate
      the possible motor cortical contribution to ET by assessing response to
      continuous theta-burst stimulation (cTBS), a recognized tool that can produce
      transient plastic changes, in the primary motor and premotor cortex of patients
      with ET. We compared parameters, including motor-evoked potential amplitude,
      cortical silent period, and short-interval intracortical inhibition, before and
      after applying cTBS in healthy controls and patients with ET. We found that,
      although cTBS applied to either the motor or premotor cortex was capable of
      producing a suppressive effect on motor cortical excitability in ET patients, the
      effects lasted for a significantly shorter time compared with the effect produced
      in healthy individuals. The change seen in measures of intracortical inhibition
      after motor cortical or premotor cTBS in healthy controls was reduced or absent
      in the ET patients. Tremor amplitude was decreased significantly after applying
      cTBS over either the motor or premotor cortex, but the tremor frequency remained
      unchanged. These findings suggest that inhibitory circuits within the motor
      cortex are aberrant and less modifiable in ET patients. The reduced plasticity in
      response to motor and premotor TBS supports the theory of abnormal gamma
      aminobutyric acid (GABA) modulation in ET.

PMID- 24449143
TI  - Laser-induced tissue fluorescence in radiofrequency tissue-fusion
      characterization.
AB  - Heat-induced tissue fusion is an important procedure in modern surgery and can
      greatly reduce trauma, complications, and mortality during minimally invasive
      surgical blood vessel anastomosis, but it may also have further benefits if
      applied to other tissue types such as small and large intestine anastomoses. We
      present a tissue-fusion characterization technology using laser-induced
      fluorescence spectroscopy, which provides further insight into tissue constituent
      variations at the molecular level. In particular, an increase of fluorescence
      intensity in 450- to 550-nm range for 375- and 405-nm excitation suggests that
      the collagen cross-linking in fused tissues increased. Our experimental and
      statistical analyses showed that, by using fluorescence spectral data, good
      fusion could be differentiated from other cases with an accuracy of more than
      95%. This suggests that the fluorescence spectroscopy could be potentially used
      as a feedback control method in online tissue-fusion monitoring.

PMID- 24449144
TI  - Wavefront holoscopy: application of digital in-line holography for the inspection
      of engraved marks in progressive addition lenses.
AB  - Progressive addition lenses (PALs) are engraved with permanent marks at
      standardized locations in order to guarantee correct centering and alignment
      throughout the manufacturing and mounting processes. Out of the production line,
      engraved marks provide useful information about the PAL as well as act as locator
      marks to re-ink again the removable marks. Even though those marks should be
      visible by simple visual inspection with the naked eye, engraving marks are often
      faint and weak, obscured by scratches, and partially occluded and difficult to
      recognize on tinted or antireflection-coated lenses. Here, we present an
      extremely simple optical device (named as wavefront holoscope) for visualization
      and characterization of permanent marks in PAL based on digital in-line
      holography. Essentially, a point source of coherent light illuminates the
      engraved mark placed just before a CCD camera that records a classical Gabor in
      line hologram. The recorded hologram is then digitally processed to provide a set
      of high-contrast images of the engraved marks. Experimental results are presented
      showing the applicability of the proposed method as a new ophthalmic instrument
      for visualization and characterization of engraved marks in PALs.

PMID- 24449145
TI  - Correlation between skin, bone, and cerebrospinal fluid layer thickness and
      optical coefficients measured by multidistance frequency-domain near-infrared
      spectroscopy in term and preterm infants.
AB  - Near-infrared spectroscopy (NIRS) is increasingly used in neonatal intensive
      care. We investigated the impact of skin, bone, and cerebrospinal fluid (CSF)
      layer thickness in term and preterm infants on absorption-(MUa) and/or reduced
      scattering coefficients (MUs') measured by multidistance frequency-domain (FD)
      NIRS. Transcranial ultrasound was performed to measure the layer thicknesses.
      Correlations were only statistically significant for MUa at 692 nm with bone
      thickness and MUs' at 834 nm with skin thickness. There is no evidence that skin,
      bone, or CSF thickness have an important effect on MUa and MUs'. Layer
      thicknesses of skin, bone, and CSF in the range studied do not seem to affect
      cerebral oxygenation measurements by multidistance FD-NIRS significantly.

PMID- 24449146
TI  - Intra-articular injection of mesenchymal stem cells for the treatment of
      osteoarthritis of the knee: a proof-of-concept clinical trial.
AB  - Mesenchymal stem cells (MSCs) are known to have a potential for articular
      cartilage regeneration. However, most studies focused on focal cartilage defect
      through surgical implantation. For the treatment of generalized cartilage loss in
      osteoarthritis, an alternative delivery strategy would be more appropriate. The
      purpose of this study was to assess the safety and efficacy of intra-articular
      injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee
      osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and
      injected AD MSCs into the knee. The phase I study consists of three dose
      escalation cohorts; the low-dose (1.0 * 10(7) cells), mid-dose (5.0 * 10(7)), and
      high-dose (1.0 * 10(8)) group with three patients each. The phase II included
      nine patients receiving the high-dose. The primary outcomes were the safety and
      the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6
      months. Secondary outcomes included clinical, radiological, arthroscopic, and
      histological evaluations. There was no treatment-related adverse event. The WOMAC
      score improved at 6 months after injection in the high-dose group. The size of
      cartilage defect decreased while the volume of cartilage increased in the medial
      femoral and tibial condyles of the high-dose group. Arthroscopy showed that the
      size of cartilage defect decreased in the medial femoral and medial tibial
      condyles of the high-dose group. Histology demonstrated thick, hyaline-like
      cartilage regeneration. These results showed that intra-articular injection of
      1.0 * 10(8) AD MSCs into the osteoarthritic knee improved function and pain of
      the knee joint without causing adverse events, and reduced cartilage defects by
      regeneration of hyaline-like articular cartilage.

PMID- 24449147
TI  - Identification of somatic alterations in stage I lung adenocarcinomas by next
      generation sequencing.
AB  - Adenocarcinoma is the most common type of lung cancer. Somatic mutations in the
      early stage of this disease have a tight relationship with tumor initiation and
      potentially activate downstream pathways that are implicated in tumor
      progression. In this study, we performed whole genome and exome sequencing of
      tumor and adjacent normal tissue from 10 patients with stage I lung
      adenocarcinoma. EGFR (4/10 tumors), BCHE (3/10), and TP53 (2/10) were identified
      recurrently with validated tumor-specific non-synonymous mutations; and the
      remaining mutations were specific to individual tumors. Computational methods
      were used to evaluate the potential effect of non-synonymous mutations on protein
      function, and putative driver mutation in genes such as SDK1 was predicted. Cell
      adhesion was the most enriched biological process in gene set analysis using the
      DAVID database. Copy number amplification at 12q15, which includes MDM2, was
      identified as a recurrent somatic alteration in 4 of 10 tumors. These findings
      provided additional information for understanding early-stage lung
      adenocarcinomas.

PMID- 24449148
TI  - Helical propensity in an intrinsically disordered protein accelerates ligand
      binding.
AB  - Many intrinsically disordered proteins fold upon binding to other macromolecules.
      The secondary structure present in the well-ordered complex is often formed
      transiently in the unbound state. The consequence of such transient structure for
      the binding process is, however, not clear. The activation domain of the
      activator for thyroid hormone and retinoid receptors (ACTR) is intrinsically
      disordered and folds upon binding to the nuclear coactivator binding domain
      (NCBD) of the CREB binding protein. A number of mutants was designed that
      selectively perturbs the amount of secondary structure in unbound ACTR without
      interfering with the intermolecular interactions between ACTR and NCBD. Using NMR
      spectroscopy and fluorescence-monitored stopped-flow kinetic measurements we show
      that the secondary structure content in helix 1 of ACTR indeed influences the
      binding kinetics. The results thus support the notion of preformed secondary
      structure as an important determinant for molecular recognition in intrinsically
      disordered proteins. 

PMID- 24449149
TI  - Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain
      tumors in children--a technical report.
AB  - BACKGROUND: 5-aminolevulinic acid (5-ALA) can be used as an adjunct for the
      surgery of adult malignant glioma and improves the rate of gross total resection
      and patient survival. So far, only three casuistic reports of fluorescence-guided
      surgery used in children have been published. We report our pilot series of 16
      pediatric brain tumors treated with 5-ALA. METHODS: Sixteen patients (mean age 9
      years, range 1-16 years) received a standardized 5-ALA dose according to the
      published protocol after informed parental consent. The fluorescence status
      (positive versus negative) in correlation with histology as well as blood samples
      and adverse clinical symptoms were recorded. RESULTS: Histology revealed
      pilocytic astrocytoma (n = 7), classical medulloblastoma (n = 4), anaplastic
      astrocytoma (n = 1), glioblastoma (n = 3) and anaplastic ependymoma (n = 1).
      Positive fluorescence was observed in cases of anaplastic astrocytoma,
      glioblastoma, and medulloblastoma, respectively. Significant increases were
      registered for alanine aminotransferase (14.92 +/- 1.106 U/l vs. 37.70 +/- 3.795
      U/l, P = 0.0020) and gamma glutamyl transpeptidase (12.69 +/- 1.638 U/l vs. 39.29
      +/- 6.342 U/l, P = 0.0156), correlated with young age. No further adverse
      reactions were evident. CONCLUSION: Positive fluorescence was observed in two
      high-grade gliomas and one medulloblastoma after oral administration of 5-ALA.
      Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade
      tumors. Adverse reactions observed in children were similar to those reported for
      adults, although very young children might be at increased risk. Further studies
      are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA
      in children and to assess its prognostic role in the resection of pediatric brain
      tumors.

PMID- 24449150
TI  - Asymmetry of tonsillar ectopia, syringomyelia and clinical manifestations in
      adult Chiari I malformation.
AB  - BACKGROUND: The asymmetry of tonsillar ectopia, syringomyelia, and clinical
      manifestations, and their correlations in adult Chiari I malformation (CIM) are
      seldom discussed. METHODS: Clinical and imaging data of 104 consecutive adult
      patients with CIM and syringomyelia were retrospectively reviewed. A method was
      devised to quantify tonsillar and syrinx asymmetry. Correlations between the
      asymmetrically displaced cerebellar tonsils, the side of the syrinx, clinical
      presentations, and the curve direction of scoliosis were investigated. RESULTS:
      Tonsillar ectopia was left dominant in 46 patients (44.2 %), right dominant in 49
      (47.1 %), and symmetrical in nine (8.7 %). The syrinx was left deviated in 44
      patients (42.3 %), right deviated in 48 (46.2 %), and centrally located in 12
      (11.5 %). A significant correlation was observed between the side of tonsillar
      herniation and the side of the syrinx (p < 0.001), and also between the
      descending ratio of tonsillar herniation and the deviation ratio of the syrinx (p
      < 0.001). The main side the of clinical presentations showed significant
      correlation with the dominant side of tonsillar herniation (p = 0.009) and the
      side of syrinx deviation (p = 0.012). In the 49 patients (47.1 %) with associated
      scoliosis, the curve direction was significantly related to not only the dominant
      side of tonsillar ectopia (p = 0.0,28) but also the deviated side of the syrinx
      (p = 0.044). Moreover, the curve magnitude was significantly correlated with the
      distance of the tonsillar herniation (p = 0.001). CONCLUSIONS: In adult CIM, most
      tonsillar herniations are asymmetrical and most syringomyelia is eccentrical. We
      speculate that the dominant side of tonsillar herniation determines the side of
      syrinx deviation, which in turn determines the main side of clinical
      presentations and the convex side of scoliosis. Our results suggest that the more
      the descended tonsil tilts to one side, the more the syrinx tilts to the same
      side.

PMID- 24449151
TI  - In situ X-ray powder diffraction studies of hydrogen storage and release in the
      Li-N-H system.
AB  - We report the experimental investigation of hydrogen storage and release in the
      lithium amide-lithium hydride composite (Li-N-H) system. Investigation of
      hydrogenation and dehydrogenation reactions of the system through in situ
      synchrotron X-ray powder diffraction experiments allowed for the observation of
      the formation and evolution of non-stoichiometric intermediate species of the
      form Li1+xNH2-x. This result is consistent with the proposed Frenkel-defect
      mechanism for these reactions. We observed capacity loss with decreasing
      temperature through decreased levels of lithium-rich (0.7 <= x <= 1.0) non
      stoichiometric phases in the dehydrogenated material, but only minor changes due
      to multiple cycles at the same temperature. Annealing of dehydrogenated samples
      reveals the reduced stability of intermediate stoichiometry values (0.4 <= x <=
      0.7) compared with the end member species: lithium amide (LiNH2) and lithium
      imide (Li2NH). Our results highlight the central role of ionic mobility in
      understanding temperature limitations, capacity loss and facile reversibility of
      the Li-N-H system. 

PMID- 24449153
TI  - The moral myopia of academic psychiatry : a response to glen o. Gabbards "the big
      chill".

PMID- 24449152
TI  - Patterns of adolescent sexual behavior predicting young adult sexually
      transmitted infections: a latent class analysis approach.
AB  - Adolescent sexual behavior is multidimensional, yet most studies of the topic use
      variable-oriented methods that reduce behaviors to a single dimension. In this
      study, we used a person-oriented approach to model adolescent sexual behavior
      comprehensively, using data from the National Longitudinal Study of Adolescent
      Health. We identified five latent classes of adolescent sexual behavior:
      Abstinent (39%), Oral Sex (10%), Low-Risk (25%), Multi-Partner Normative (12%),
      and Multi-Partner Early (13%). Membership in riskier classes of sexual behavior
      was predicted by substance use and depressive symptoms. Class membership was also
      associated with young adult STI outcomes although these associations differed by
      gender. Male adolescents' STI rates increased with membership in classes with
      more risky behaviors whereas females' rates were consistent among all sexually
      active classes. These findings demonstrate the advantages of examining adolescent
      sexuality in a way that emphasizes its complexity.

PMID- 24449154
TI  - Recommendations from the may 1992 conference to enhance recruitment of u.s.
      Medical graduates into psychiatry.
AB  - From 1988 to 1993, recruitment of U.S. medical graduates into psychiatry has
      declined by more than one-third. This decline threatens to further exacerbate the
      shortage of psychiatrists projected by the Council on Graduate Medical Education.
      In May 1992, the American Association of Directors of Psychiatric Residency
      Training sponsored a 2-day conference to develop specific courses of action and
      an overall strategy to reverse this de-cline. Key recommendations from the
      conference are presented. The proposed actions are presented in a format that
      identifies the appropriate medical, educational, or psychiatric organization
      charged with a specific action's implementation. 

PMID- 24449155
TI  - Living and learning with managed care.
AB  - As the external forces of managed health care change the face of clinical
      services, residency training programs are confronted with complex clinical,
      programmatic, administrative, didactic, and psychological issues. The authors
      outline one program's response to these training challenges and survey a variety
      of problems commonly encountered by residents and supervisors. 

PMID- 24449156
TI  - The black woman academic psychiatrist.
AB  - The various influences contributing to the decision of black women psychiatric
      residents to select a career in academic medicine are explored. The role of
      mentors and national fellowships in facilitating the development of the
      professional identity of black psychiatrists are discussed. The complexity of a
      black woman as an academic psychiatrist is presented in the context of examples
      of coping strategies. These strategies ameliorate negative interactions and
      anticipated questions of competence, leadership, and the effective mastery of
      confrontation. Specific experiences unique to the black academic psychiatrist,
      including the effect of gender and race on various interactions, are illustrated.
      Career development, from the first academic position following residency training
      to the transition to associate professor, are reviewed with attention to the
      specific concerns unique to each stage. 

PMID- 24449157
TI  - Effectiveness of an Educational Intervention Session in Changing Student
      Attitudes and Beliefs About HIV : Impact of an Interview With an HIV-infected
      Physician.
AB  - In this study, 170 preclinical students completed a 12-statement baseline survey
      designed to measure their attitudes and beliefs about the human immunodeficiency
      virus (HIV) and the acquired immunodeficiency syndrome (AIDS) 4 weeks before
      interviewing an HIV-infected physician. Eight weeks later, 152 students completed
      a follow-up survey to see if any changes or shifts occurred on any of their
      initial responses. Pre- and post-session survey responses of 88 students who had
      attended the intervention 4 weeks before and 64 who had not were compared. The
      attendees had statistically significant shifts in their responses on 7 of 12
      survey items. The nonattendees had a small but significant ship on only one
      survey item. This pilot intervention appears to be effective in not only
      persistently changing some students' attitudes and beliefs about HIV and AIDS,
      but also in instilling empathic and positive professional attitudes toward
      treating persons with HIV and AIDS. 

PMID- 24449158
TI  - Letter.

PMID- 24449159
TI  - Frequently asked questions by psychiatric residency training directors.

PMID- 24449161
TI  - Multilevel ordinal factor analysis of the positive and negative syndrome scale
      (PANSS).
AB  - Clinical assessments of the presence and severity of psychopathology are often
      collected by health care professionals in mental health services or clinical
      researchers trained to use semi-structured interviews. Clustering by interviewer
      or rater needs to be considered when performing psychometric analyses such as
      factor analysis or item response modelling as non-independence of observations
      arises in these situations. We apply more suitable multilevel methods to analyse
      ordinally scored Positive and Negative Syndrome Scale (PANSS) items. Our aim is
      to highlight the differences in results that occur when the data are analysed
      using a hierarchically sensitive approach rather than using a traditional
      (aggregated) analysis. Our sample (n = 507) consisted of patients diagnosed with
      schizophrenia who participated in a multi-centre randomized control clinical
      trial, the DIALOG study. Analyses reported and compared include an exploratory
      factor analysis as well as several recently published multifactor models re
      estimated within a confirmatory analysis framework. Our results show that the fit
      of the model and the parsimony of the exploratory factor analysis (EFA) models
      indicated by the number of factors necessary to explain the inter-correlation
      among PANSS items improved significantly when data clustering is taken into
      account through multilevel analysis. Our modeling results support the pentagonal
      PANSS model first proposed by White et al. (1997). Copyright (c) 2014 John Wiley
      & Sons, Ltd. 

PMID- 24449162
TI  - A plea for patience and research on surface water connectivity in the U.S. Clean
      Water Act.
AB  - While winter has proven to be one of the coldest and snowiest seasons on record
      throughout much of the United States, the coming summer could be unseasonably
      warm in Washington, DC if the United States Environmental Protection Agency
      (USEPA) successfully implements its reinterpretation of one of the nation's
      proudest environmental regulatory accomplishments, the Clean Water Act (CWA). In
      2013, USEPA and the US Army Corps of Engineers (Corps) bypassed the traditional
      scientific review and public comment process by submitting to the Office of
      Management and Budget (OMB) a proposed rule establishing a broad interpretation
      of the scope of the forty year old CWA. In the US, the OMB is tasked, among other
      duties, with evaluating the significance of agency policies and proposed
      regulations on the national economy. Integr Environ Assess Manag (c) 2014 SETAC.

PMID- 24449163
TI  - Author's response to 'Complete (EBUS and EUS) endosonographic staging of lung
      cancer'.

PMID- 24449164
TI  - Maternal consumption of trans-fatty acids during the first half of gestation are
      metabolically available to suckled newborn rats.
AB  - Dietary trans-fatty acids (t-FA) during pregnancy have adverse effects on growth
      and development. To determine the effect of dietary t-FA during just the first
      half of pregnancy, rats were given a diet containing 8 % hydrogenated peanut oil
      and 2 % olive oil (PO) and compared to rats given a diet containing 10 % olive
      oil (OO). After 12 days all rats were fed standard diet and were studied at days
      12 or 20 of pregnancy or days 1 or 6 postpartum. At day 12 of pregnancy there
      were small differences in the plasma and lumbar adipose tissue fatty acid
      profiles and elaidic acid [18:1(n-9)t] was present in the PO group. From day 12
      to 20 of pregnancy, plasma non-esterified fatty acids, glycerol, triacylglycerols
      (TAG) and most individual fatty acids increased more in PO than in OO. At day 20
      of pregnancy in the PO group most plasma elaidic acid appeared as plasma TAG and
      was also present in the mammary gland, to decline in both sites at day 1
      postpartum. Elaidic acid concentration was low in the plasma of 20-day fetuses,
      increased in 1-day newborns declining at day 6. Thus t-FA, eaten during early
      pregnancy, accumulated in maternal adipose tissue and were released during late
      pregnancy to be taken up by the mammary gland becoming available to the newborns
      during suckling. 

PMID- 24449165
TI  - Enantioselective disruption of the endocrine system by Cis-Bifenthrin in the male
      mice.
AB  - Bifenthrin (BF), as a chiral pyrethroid, is widely used to control field and
      household pests in China. At present, the commercial BF is a mixed compound
      containing cis isomers (cis-BF) including two enantiomers of 1R-cis-BF and 1S-cis
      BF. In the present study, the two individual cis-BF enantiomers were separated by
      a preparative supercritical fluid chromatography. Then, four week-old adolescent
      male ICR mice were orally administered 1R-cis-BF and 1S-cis-BF separately daily
      for 3 weeks at doses of 0, 7.5 and 15 mg/kg/day, respectively. Results showed
      that the transcription status of some genes involved in cholesterol synthesis and
      transport as well as testosterone (T) synthesis in the testes were influenced by
      cis-BF enantiomers. Especially, we observed that the transcription status of key
      genes on the pathway of T synthesis including cytochrome P450 cholesterol side
      chain cleavage enzyme (P450scc) and cytochrome P450 17alpha-hydroxysteroid
      dehydrogenase (P45017alpha)) were selectively altered in the testis of mice when
      treated with 1S-cis-BF, suggesting that it is the possible reason to explain why
      the lower serum T concentration in 1S-cis-BF treated group. Taken together, it
      concluded that both of the cis-BF enantiomers have the endocrine disruption
      activities, while 1S-cis-BF was higher than 1R-cis-BF in mice when exposed during
      the puberty. The data was helpful to understand the toxicity of cis-BF in mammals
      under enantiomeric level.

PMID- 24449166
TI  - Ultrasonographic features of renal oncocytoma with histopathologic correlation.
AB  - BACKGROUND: To analyze the sonographic (US) features of renal oncocytoma and
      correlate them with histopathologic findings. METHODS: The medical records of 12
      patients with a histologic diagnosis of renal oncocytomas were reviewed. The
      location, size, shape, margin, echogenicity, homogeneity, and blood flow
      distribution of the lesions were analyzed, and the US features were compared with
      histopathologic findings. RESULTS: Oncocytomas appeared as solid, solitary, well
      marginated, unencapsulated, fairly homogeneous renal cortical masses (n = 10),
      with regular shape, relatively isoechoic (n = 5) or slightly hyperechoic (n = 7)
      to the adjacent renal parenchyma, and an exophytic growth pattern was exhibited
      in most cases (n = 9). Two larger masses (>=9 cm) demonstrated a central stellate
      scar and a characteristic of spoke-wheel vascular pattern. The tumors with a low
      percentage of stroma (<20%) were associated with an echotexture isoechoic to
      renal parenchyma, whereas oncocytomas with a higher percentage of stroma (>20%)
      were slightly hyperechoic. CONCLUSIONS: Although the US features are not
      pathognomonic, their presence should alert to the possible diagnosis of renal
      oncocytoma.

PMID- 24449167
TI  - Enteral glutamine infusion modulates ubiquitination of heat shock proteins, Grp
      75 and Apg-2, in the human duodenal mucosa.
AB  - Glutamine, the most abundant amino acid in the human body, plays several
      important roles in the intestine. Previous studies showed that glutamine may
      affect protein expression by regulating ubiquitin-proteasome system. We thus
      aimed to evaluate the effects of glutamine on ubiquitinated proteins in human
      duodenal mucosa. Five healthy male volunteers were included and received during 5
      h, on two occasions and in a random order, either an enteral infusion of
      maltodextrins alone (0.25 g kg(-1) h(-1), control), mimicking carbohydrate-fed
      state, or maltodextrins with glutamine (0.117 g kg(-1) h(-1), glutamine).
      Endoscopic duodenal biopsies were then taken. Total cellular protein extracts
      were separated by 2D gel electrophoresis and analyzed by an immunodetection using
      anti-ubiquitin antibody. Differentially ubiquitinated proteins were then
      identified by liquid chromatography-electrospray ionization MS/MS. Five proteins
      were differentially ubiquitinated between control and glutamine conditions. Among
      these proteins, we identified two chaperone proteins, Grp75 and hsp74. Grp75 was
      less ubiquitinated after glutamine infusion compared with control. In contrast,
      hsp74, also called Apg-2, was more ubiquitinated after glutamine. In conclusion,
      we provide evidence that glutamine may regulate ubiquitination processes of
      specific proteins, i.e., Grp75 and Apg-2. Grp75 has protective and anti
      inflammatory properties, while Apg-2 indirectly regulates stress-induced cell
      survival and proliferation through interaction with ZO-1. Further studies should
      confirm these results in stress conditions.

PMID- 24449168
TI  - Brief report: Loss of p15Ink4b accelerates development of myeloid neoplasms in
      Nup98-HoxD13 transgenic mice.
AB  - Homeostasis of hematopoietic stem and progenitor cells is a tightly regulated
      process. The disturbance of the balance in the hematopoietic progenitor pool can
      result in favorable conditions for development of diseases such as
      myelodysplastic syndromes and leukemia. It has been shown recently that mice
      lacking p15Ink4b have skewed differentiation of common myeloid progenitors toward
      the myeloid lineage at the expense of erythroid progenitors. The lack of p15INK4B
      expression in human leukemic blasts has been linked to poor prognosis and
      increased risk of myelodysplastic syndromes transformation to acute myeloid
      leukemia. However, the role of p15Ink4b in disease development is just beginning
      to be elucidated. This study examines the collaboration of the loss of p15Ink4b
      with Nup98-HoxD13 translocation in the development of hematological malignancies
      in a mouse model. Here, we report that loss of p15Ink4b collaborates with Nup98
      HoxD13 transgene in the development of predominantly myeloid neoplasms, namely
      acute myeloid leukemia, myeloproliferative disease, and myelodysplastic
      syndromes. This mouse model could be a very valuable tool for studying p15Ink4b
      function in tumorigenesis as well as preclinical drug testing.

PMID- 24449169
TI  - Low-frequency subthalamic nucleus stimulation in Parkinson's disease: a
      randomized clinical trial.
AB  - BACKGROUND: Low-frequency, bilateral stimulation of the subthalamic nucleus can
      improve axial symptoms of advanced Parkinson's disease (PD), but it is not
      particularly effective for segmental symptoms. METHODS: The optimal contacts for
      low-frequency (60 Hz) and high-frequency (130 Hz) single monopolar stimulation
      were determined. Then, in a randomized, double-blind, prospective crossover
      manner, 60-Hz and 130-Hz stimulations via the respective optimal contacts were
      compared for immediate efficacy in improving the motor function of patients with
      PD. RESULTS: The optimal contacts for 60-Hz stimulation were situated more
      ventrally than those for 130-Hz stimulation (P = 0.038). Under the respective
      optimal, single monopolar stimulation, 60 Hz provided superior efficacy over 130
      Hz in improving the total Unified Parkinson's Disease Rating Scale motor score (P
      < 0.001) and the akinesia (P = 0.011) and axial motor signs (P = 0.012) subscores
      without compromising the therapeutic effect on tremor and rigidity. CONCLUSIONS:
      Low-frequency stimulation via the optimal contacts is effective in improving
      overall motor function of patients with PD.

PMID- 24449171
TI  - Minimizing blood loss during hepatectomy: a literature review.
AB  - There are numerous techniques surgeons employ to reduce blood loss during partial
      hepatectomy. In this literature review, prospective studies from the last 20
      years are examined to determine the techniques that are best supported by the
      literature. Some of the techniques include vascular control, multiple parenchymal
      transection techniques, various hemostatic agents, low central venous pressure,
      and hemodilution. The strategies supported most convincingly by the literature
      include low CVP and total hepatic inflow occlusion.

PMID- 24449170
TI  - Rumination and overgeneral autobiographical memory in adolescents: an integration
      of cognitive vulnerabilities to depression.
AB  - During adolescence, rates of depression dramatically increase and girls become
      twice as likely as boys to develop depression. Research suggests that overgeneral
      autobiographical memory and rumination are vulnerability factors for depressive
      symptoms in adolescence that may be triggered by stressful life events. The
      current longitudinal study included 160 early adolescents (Mage = 12.44 years,
      60.0 % African American, 40.0 % Caucasian, and 56.2 % female). At baseline,
      adolescents completed measures of current depressive symptoms, rumination, and
      specificity of autobiographical memories. Approximately 9 months later, the
      adolescents completed measures of current depressive symptoms and stressful life
      events that had occurred between baseline and follow-up. Analyses indicated that
      girls with more overgeneral autobiographical memories in combination with higher
      levels of rumination were most vulnerable to experiencing increases in depressive
      symptoms following stressful life events. Additionally, retrieving more specific
      autobiographical memories appeared to buffer against the impact of negative life
      events on depressive symptoms among both boys and girls. Memory specificity may
      play a protective role in depression risk, suggesting that memory specificity
      training interventions may prove beneficial for adolescents.

PMID- 24449172
TI  - Cytoreduction and heated intraperitoneal chemotherapy for colorectal cancer: are
      we excluding patients who may benefit?
AB  - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) are increasingly used to treat peritoneal carcinomatosis
      from colorectal cancer. It is still relatively unknown which poor prognostic
      factors to avoid in order to optimize patient selection for CRS + HIPEC. METHODS:
      Between February 2003 and October 2011, 68 consecutive colorectal cancer patients
      who underwent CRS + HIPEC with a complete cytoreduction were identified from a
      prospective database. Survival analysis was performed using the Kaplan-Meier
      method, with log rank testing of differences between groups. Multivariate
      analysis was conducted using Cox proportional hazard regression. RESULTS: Median
      follow-up was 30.3 (range, 2-88) months amongst survivors. Patients with a
      peritoneal cancer index (PCI) of 10 or less showed improved survival over those
      with a PCI of 11 or higher (P = 0.03). No difference in survival was seen for the
      other potentially poor prognostic variables including lymph node status,
      synchronous peritoneal disease, peri-operative systemic chemotherapy, and rectal
      cancer primary. CONCLUSIONS: A low PCI was associated with improved survival.
      Complete CRS + HIPEC appears to result in similar survival outcomes regardless of
      delivery of peri-operative systemic chemotherapy. Rectal origin, lymph node
      status, and synchronous peritoneal disease should not be used as an absolute
      exclusion criteria for CRS + HIPEC based on current data.

PMID- 24449173
TI  - Vascular progenitor clusters from peripheral blood in cancer patients following
      oncologic surgery.
AB  - INTRODUCTION: Vascular progenitor cells (VPCs) are recruited into the peripheral
      blood (PB) following ischemia and inflammation and correlate with vascular
      health. The impact of recruiting VPCs on surgical recovery and cancer progression
      following tumor resection remain unknown. METHODS: We measured VPC clusters and
      enumerated circulating CD34+ VEGFR2+ angiogenic cells in 18 patients with oral
      cancer (OC) undergoing resection and free flap reconstruction (high vascular
      injury) and in 18 patients undergoing colorectal cancer resection (CRC) (low
      vascular injury) at baseline and multiple timepoints after surgery. RESULTS: VPC
      clusters increased following OC resection, peaking on Day +3 and returning to
      baseline by Day 28. In contrast, VPC clusters decreased sharply on Day +3 in
      patients with CRC before returning to baseline. CD34+ VEGFR2+ cells did not
      increase significantly after surgery. More rapid clinical recovery following OC
      resection was observed in patients with greater VPC cluster levels on Day +3.
      Tumor size and subsequent progression of cancer did not correlate with
      recruitment of VPC cluster-forming cells. CONCLUSION: VPC recruitment following
      cancer resection may depend on cancer subtype and may relate to the degree of
      surgical stress and vascular injury. Recovery after surgery for OC may be
      accelerated in patients with greater VPC recruitment.

PMID- 24449174
TI  - Endovascular treatment with flow diverters of recanalized and multitreated
      aneurysms initially treated by endovascular approach.
AB  - PURPOSE: To evaluate the feasibility, safety and efficacy of endovascular
      treatment with flow diverters in patients with recanalized and multitreated
      aneurysms in a retrospective, multicenter, single-arm study. METHODS: The study
      included 29 patients with 29 recanalized aneurysms who were treated by flow
      diverters (Silk or Pipeline devices). Pre- and post-procedural complications and
      morbidity and mortality rates were evaluated and functional outcomes (modified
      Rankin Score (mRS)) at 1 month (short-term) and 3-4 months (mid-term) were
      compared with preoperative mRS (before the procedure). Mid-term angiographic
      follow-up was performed assessing aneurysmal occlusion by the Montreal scale
      (complete occlusion, neck remnant, aneurysm remnant). RESULTS: Placement of the
      flow diverters was achieved in all patients. Two misdeployments of the flow
      diverters necessitated balloon dilation in two patients, which was associated
      with stent delivery in one patient. Permanent morbidity related to treatment was
      6.9% (2/29), transient morbidity was 10.3% (3/29) and there were no deaths
      resulting from the treatment. One patient died from a myocardial infarct 4 weeks
      after the procedure. 25/29 patients (86.2%) had a good final functional outcome,
      26/29 (89.7%) had an unchanged functional outcome and 2/29 patients (6.9%) had
      clinical worsening. Angiographic follow-up showed complete occlusion in 17/28
      patients (60.7%), neck remnants in 6/28 patients (21.4%) and residual aneurysms
      in 5/28 (17.9%). CONCLUSIONS: Flow diverter placement is feasible and safe in
      patients with recanalized and multitreated aneurysms. The procedure is associated
      with a high percentage of good functional outcomes as well as good mid-term
      anatomical results (82.1%).

PMID- 24449175
TI  - A column-switching HPLC-MS/MS method for mucopolysaccharidosis type I analysis in
      a multiplex assay for the simultaneous newborn screening of six lysosomal storage
      disorders.
AB  - Lysosomal storage disorders comprise a group of rare genetic diseases in which a
      deficit of specific hydrolases leads to the storage of undegraded substrates in
      lysosomes. Impaired enzyme activities can be assessed by MS/MS quantification of
      the reaction products obtained after incubation with specific substrates. In this
      study, a column-switching HPLC-MS/MS method for multiplex screening in dried
      blood spot of the lysosomal enzymes activities was developed.
      Mucopolysaccharidosis type I, Fabry, Gaucher, Krabbe, Niemann-Pick A/B and Pompe
      diseases were simultaneously assayed. Dried blood spots were incubated with
      substrates and internal standards; thereafter, supernatants were collected with
      minor manipulations. Samples were injected, trapped into an online perfusion
      column and, by a six-port valve, switched online through the C18 analytical
      column to perform separation of metabolites followed by MS/MS analysis. A total
      of 1136 de-identified newborn screening samples were analyzed to determine
      references for enzymes activity values. As positive controls, we analyzed dried
      blood spots from three patients with Pompe, one with Fabry, one with Krabbe
      disease and two with MPS I, and in all cases the enzyme activities were below the
      cutoff values measured for newborns, except for an MPS I patient after successful
      hematopoietic stem cell transplantation.

PMID- 24449176
TI  - Astrochemistry.

PMID- 24449177
TI  - Advanced materials and nanotechnology for drug delivery.
AB  - Many biological barriers are of great importance. For example, stratum corneum,
      the outmost layer of skin, effectively protects people from being invaded by
      external microorganisms such as bacteria and viruses. Cell membranes help
      organisms maintain homeostasis by controlling substances to enter and leave
      cells. However, on the other hand, these biological barriers seriously restrict
      drug delivery. For instance, stratum corneum has a very dense structure and only
      allows very small molecules with a molecular weight of below 500 Da to permeate
      whereas most drug molecules are much larger than that. A wide variety of drugs
      including genes needs to enter cells for proper functioning but cell membranes
      are not permeable to them. To overcome these biological barriers, many drug
      delivery routes are being actively researched and developed. In this research
      news, we will focus on two advanced materials and nanotechnology approaches for
      delivering vaccines through the skin for painless and efficient immunization and
      transporting drug molecules to cross cell membranes for high-throughput
      intracellular delivery. 

PMID- 24449178
TI  - Dipole-induced band-gap reduction in an inorganic cage.
AB  - Metal-doped polyoxotitanium cages are a developing class of inorganic compounds
      which can be regarded as nano- and sub-nano sized molecular relatives of metal
      doped titania nanoparticles. These species can serve as models for the ways in
      which dopant metal ions can be incorporated into metal-doped titania (TiO2 ), a
      technologically important class of photocatalytic materials with broad
      applications in devices and pollution control. In this study a series of
      cobalt(II)-containing cages in the size range ca. 0.7-1.3 nm have been
      synthesized and structurally characterized, allowing a coherent study of the
      factors affecting the band gaps in well-defined metal-doped model systems. Band
      structure calculations are consistent with experimental UV/Vis measurements of
      the Tix Oy absorption edges in these species and reveal that molecular dipole
      moment can have a profound effect on the band gap. The observation of a dipole
      induced band-gap decrease mechanism provides a potentially general design
      strategy for the formation of low band-gap inorganic cages. 

PMID- 24449179
TI  - Resorption of mandibular alveolar bone following loss of molar teeth and its
      relationship to age at death in a human skeletal population.
AB  - Estimating adult age at death in skeletal remains is problematic, particularly in
      older adults. Molar wear is arguably the most reliable ageing technique for
      palaeopopulations, but many older adult skeletons have lost their molar teeth
      ante mortem, precluding its application. Resorption of the alveolar process
      occurs following tooth loss, and this appears to continue for a prolonged period.
      The current work investigates the relationship of this process to individual age
      in a nineteenth century AD European archaeological skeletal series of known age
      at death (N = 92 individuals), and discusses its potential as an age indicator.
      Mandibular corpus height was measured at the different molar positions. In
      females, reduction of corpus height with age was found at molar positions showing
      ante mortem loss. In both sexes, a relationship was found between age and a
      simple composite measure of corpus height in the molar region in those showing
      ante mortem loss of one or more mandibular molars. The correlation was stronger
      in females (r = -0.74) than in males (r = -0.49), appeared approximately linear,
      and continued into the ninth decade, the oldest age group in the study material.
      The results suggest that investigation of height of the posterior part of the
      mandibular corpus as a skeletal age indicator for individuals that have lost one
      or more molar teeth is merited in other palaeopopulations.

PMID- 24449181
TI  - Isolation and characterization of 14 polymorphic microsatellite loci in the big
      headed turtle (Platysternon megacephalum).
AB  - The big-headed turtle (Platysternon megacephalum) is critically endangered
      because of overharvesting, illegal trade, and habitat destruction. Assessment of
      genetic variability in existing populations becomes very important to the
      taxonomy and conservation of this species. Here we describe 14 microsatellite
      loci isolated from an enriched genomic library of the big-headed turtle, and the
      polymorphisms of these loci were assessed in 28 individuals from Huizhou, Heyuan,
      Zhaoqing, and Shaoguan of Guangdong, China. The range of polymorphism information
      content is 0.305-0.738, and no evidence of significant linkage disequilibrium was
      found among any pairs of loci. These 14 new polymorphic microsatellite loci can
      be used in population genetics, taxonomy, phylogeography, behavior ecology, and
      conservation efforts of Platysternon megacephalum. 

PMID- 24449180
TI  - Simultaneous detection of multiple targets for ultrastructural
      immunocytochemistry.
AB  - Simultaneous detection of biological molecules by means of indirect
      immunolabeling provides valuable information about their localization in cellular
      compartments and their possible interactions in macromolecular complexes. While
      fluorescent microscopy allows for simultaneous detection of multiple antigens,
      the sensitive electron microscopy immunodetection is limited to only two
      antigens. In order to overcome this limitation, we prepared a set of novel, shape
      coded metal nanoparticles readily discernible in transmission electron microscopy
      which can be conjugated to antibodies or other bioreactive molecules. With the
      use of novel nanoparticles, various combinations with commercial gold
      nanoparticles can be made to obtain a set for simultaneous labeling. For the
      first time in ultrastructural histochemistry, up to five molecular targets can be
      identified simultaneously. We demonstrate the usefulness of the method by mapping
      of the localization of nuclear lipid phosphatidylinositol-4,5-bisphosphate
      together with four other molecules crucial for genome function, which proves its
      suitability for a wide range of biomedical applications. 

PMID- 24449182
TI  - A curriculum for learning about american indians and alaska natives in psychiatry
      residency training.
AB  - EDITOR'S NOTE: This article is the the third of six residency training curricula
      written for psychiatric educators by members of the American Psychiatric
      Association's (APA) minority and underrepresented component committees. The first
      curriculum (on homosexuality) appeared in the Summer 1994 issue of Academic
      Psychiatry, the second curriculum (on gender and women's issues) in the Winter
      1995 issue. Commissioned by the APA Assembly, these curricula are intended to
      represent collectively a state-of-the-art description of psychiatric residency
      training regarding the needs of individuals from minority and traditionally
      underrepresented populations within the United States. They may be seen as a
      companion work to the growing body of clinically oriented volumes on the subject
      of the interaction of culture, ethnicity, and psychiatry. They are valuable
      resources and serve as guideposts for psychiatric educators. The remaining three
      curricula will appear in upcoming issues.A curriculum is pro posed for teaching
      psychiatric residents about the diagnosis and treatment of American Indians and
      Alaska Natives. The historical context, contemporary myths, and the rationale for
      the inclusion of curriculum materials on Indians in residency training are
      presented. The curriculum for the 4 years of residency training is then briefly
      described, and the knowledge, skills, and attitudes needed by residents are
      outlined. In postgraduate year (PGY)-1 and PGY-2, the curriculum includes a basic
      history and description of Indian people, information on myths about the group,
      and psychiatric epidemiology and psychopathology. In PGY-3, information is
      included on clinical care, as well as on related areas such as service
      utilization and illness prevention. In PGY-4, a seminar is proposed in which
      psychotherapy and other clinical cases are discussed. (Academic Psychiatry 1996;
      20:5-14).

PMID- 24449183
TI  - A survey of child and adolescent psychiatry residents : demographic
      characteristics, program selection factors, training satisfaction, and career
      choice.
AB  - This study attempted to discover how child and adolescent psychiatry residents
      chose their training programs, what they intended to do with their careers, and
      how they perceived their educational experiences. The survey was distributed to
      all psychiatry residents in the United States through their training directors in
      1990. The authors received 310 responses. Significant differences were noted
      between male and female residents. Most residents expressed an intention to go
      into private practice after training. There were significant differences in
      residents interested in private practice vs. academic careers. The residents had
      applied to comparatively few programs and made training decisions early. The
      study generated objective information that may yield more specific recruitment
      strategies for child and adolescent psychiatry. 

PMID- 24449184
TI  - Resident and faculty evaluations of a psychiatry night-float system.
AB  - This study used self-report questionnaires to examine resident and faculty
      perceptions of a new night-float schedule for coverage of a psychiatric emergency
      room compared with a traditional night-call system. The residents reported
      improved well-being, educational experience, and performance of clinical duties
      under the night-float system compared with a traditional call schedule. The
      faculty had a generally favorable impression of the new system. Night-float
      systems may provide a means of improving psychiatric residents' emergency room
      and outpatient experiences without compromising patient care, although further
      studies are needed to measure fully the cost-benefit ratio of such programs. 

PMID- 24449185
TI  - Medical students' attitudes on specialist physicians' social and sexual contact
      with patients.
AB  - To assess medical students' attitudes toward social and sexual contact with
      patients by physicians from three medical specialties (internal medicine,
      obstetrics-gynecology, and psychiatry), 326 students were surveyed at one medical
      school and 239 students responded (response rate = 73.3%). Most students
      perceived that arranging to date and/or dating and genital sexual contact were
      not appropriate either during a patient visit or concurrent with ongoing
      treatment. However, as many as 20% of the male students and 3.5% of the female
      students said that genital sexual contact with patients concurrent with treatment
      was (sometimes or usually) appropriate, depending on the specialty. Significant
      gender differences were found in attitudes about physician-patient sexual
      contact. Genital sexual contact was also significantly less likely to be
      perceived as appropriate for psychiatrists, as might be expected, than for
      obstetrician-gynecologists and internal medicine specialists. These results are
      discussed in relation to current codes of ethics. 

PMID- 24449186
TI  - A pilot course for residents on sexual feelings and boundary maintenance in
      treatment.
AB  - Surveys indicate that between 6% and 10% of psychiatrists report sexual contact
      with patients. Surveys also indicate that only a small minority of psychiatrists
      feel that they have received adequate teaching about this unethical behavior.
      Educational efforts aimed at reducing sexual exploitation of patients would be of
      value to trainees, patients, academic programs, and the profession. The authors
      report their experience with a pilot 6-session course for residents, and a longer
      model course is outlined. Such education should be mandatory in U.S. residencies.
      Mandated instruction would be consistent with both the high priority training
      directors have reported placing on the subject of sexual misconduct in ethics
      teaching, and with the widespread calls for increased education on this important
      subject. 

PMID- 24449187
TI  - Psychiatric education at a veterans affairs medical center.
AB  - The authors describe how a small and relatively low-functioning psychiatric
      teaching program at a Department of Veterans Affairs (VA) medical center was
      transformed over a 6-year period into an active and well-functioning program for
      both medical students and residents. Steps were taken to address trainees'
      negative perceptions about VA patients and faculty, recruit and support an
      education-oriented staff, and improve the "user-friendliness" of the system.
      Efforts were made to integrate education into the missions of a variety of
      clinical and research programs while emphasizing the convergence of trends in the
      field of psychiatry with the VA experience. Data are presented indicating
      improvements in student and resident evaluations. Training was significantly
      expanded on inpatient units, chemical dependence units, a research unit, and an
      outpatient clinic. The authors offer suggestions that may be helpful to those
      developing psychiatric education at other academically affiliated VA medical
      centers. 

PMID- 24449188
TI  - Encapsulation of acetylshikonin by polyamidoamine dendrimers for preparing
      prominent nanoparticles.
AB  - Acetylshikonin (AS) has demonstrated antitumor potential. However, the
      development of therapeutic applications utilizing AS is inhibited by its poor
      solubility in water. In the present work, polyamidoamine (PAMAM) dendrimers and
      their PEGylated derivatives were employed to increase the solubility of AS. A
      distinct color transition was observed during the encapsulation of AS suggesting
      strong intermolecular forces between PAMAM and AS. Ultraviolet-visible, high
      performance liquid chromatography, and (1)H NMR were used to verify the
      interaction between PAMAM and AS. The maximum amount of combined AS to each PAMAM
      molecule was determined. The cytotoxicity of AS nanoparticles was evaluated
      against leukemia (K562) and breast cancer (SK-BR-3) cell lines; the AS
      nanoparticles were shown to effectively inhibit tumor cells. 

PMID- 24449189
TI  - ZnS nanoarchitectures induced dysfunction of vascular endothelial cells in vitro
      and in vivo.
AB  - ZnS nanoarchitectures have been intensively investigated recently because of
      their applications in optoelectronics and adsorption capacity. The potential
      hazard of ZnS nanoarchitectures is not well known. In this study, we investigated
      the toxicity of ZnS nanoarchitectures on vascular endothelial cell (VEC) in vitro
      and in vivo. The results showed that ZnS could inhibit human umbilical vein
      endothelial cell (HUVEC) proliferation at 50 and 200 MUg/mL. Endothelial nitric
      oxide synthase (eNOS) activity, nitric oxide (NO), and reactive oxygen species
      productions were increased, which was companied with the decrease in caveolin-1
      level. The endothelium of the aortic root was damaged and the NO levels in serum
      were elevated in the mice treated with 5 or 10 mg/kg ZnS for 3 and 6 days, but
      the body could repair the damage. The data suggested that the high concentration
      of ZnS could induce dysfunction of VECs through decreasing caveolin-1 and
      elevation of the eNOS activity and thus present toxicity.

PMID- 24449190
TI  - Human temporal lobe epilepsy analyses by tissue proteomics.
AB  - Although there are many types of epilepsy, temporal lobe epilepsy (TLE) is
      probably in humans the most common and most often studied. TLE represents 40% of
      the total epilepsy form of the disease and is difficult to treat. Despite a
      wealth of descriptive data obtained from the disease history of patients, the EEG
      recording, imaging techniques, and histological studies, the epileptogenic
      process remains poorly understood. However, it is unlikely that a single factor
      or a single mechanism can cause many changes associated with this
      neuropathological phenomenon. MALDI mass spectrometry imaging (MSI) coupled to
      protein identification, because of its ability to study a wide range of
      molecules, appears to be suitable for the preparation of molecular profiles in
      TLE. Seven neuropeptides have been have been identified in Dental gyrus regions
      of the hippocampus in relation with TLE pathology. Shot-gun studies taking into
      account gender influence have been performed. Tissue microextraction from control
      (10) toward 10 TLE patients have been analyzed after trypsin digestion followed
      by separation on nanoLC coupled to LTQ orbitrap. From the shot-gun analyses,
      results confirmed the presence of specific neuropeptides precursors and receptors
      in TLE patients as well as proteins involved in axons regeneration including
      neurotrophins, ECM proteins, cell surface proteins, membrane proteins, G
      proteins, cytoskeleton proteins and tumor suppressors. Among the tumor
      suppressors identified, the Leucine-rich glioma inactivated 1 (LGI1) protein was
      found. LGI1 gene recently been demonstrated being implicated in heritability of
      TLE. We have also demonstrate the presence a complete profile of tumor
      suppressors in TLE patients, 7 have been identified. Refining this analysis taken
      into account the gender influence in both control and in TLE reflected the
      presence of specific proteins between male and female and thus mechanisms in
      pathology development could be completely different.

PMID- 24449192
TI  - Recurrence rates of bipolar disorder during the postpartum period: a study on 276
      medication-free Italian women.
AB  - The postpartum period is considered a time of heightened vulnerability to bipolar
      disorder. The primary goal of this study was to examine the frequency and the
      polarity of postpartum episodes in a clinical sample of women with bipolar
      disorder who were medication-free during their pregnancies. In addition, we
      sought to examine whether there are differences in terms of clinical features of
      bipolar disorder between women with and without postpartum episodes. Lastly, we
      analyzed the potential relationship between polarity of the postpartum episodes
      and clinical features of bipolar disorder. The presence/absence of postpartum
      episodes and their characteristics were obtained from medical records of 276
      women with bipolar disorder who were medication-free during their pregnancies.
      Two hundred seven women (75.0 %) had a history of one or more postpartum mood
      episodes: depressive (79.7 %), (hypo)manic (16.4 %), or mixed episodes (3.9 %).
      Psychotic symptoms during postpartum episodes were associated with depression in
      37 (22.4 %) patients, with mania in 19 (67.8 %) patients, and with mixed episodes
      in 7 (87.5 %) patients. Postpartum manic and mixed episodes were significantly
      associated with type I disorder and with psychotic features. Our findings
      indicate high risk of clinically ascertained mood episodes during postpartum
      period in bipolar women who are not treated during pregnancy.

PMID- 24449191
TI  - CALM Pregnancy: results of a pilot study of mindfulness-based cognitive therapy
      for perinatal anxiety.
AB  - Many women experience anxiety during pregnancy with potential negative effects on
      maternal, birth, and child outcomes. Because of potential risks of fetal exposure
      to psychotropic medications, efficacious non-pharmacologic approaches are
      urgently needed. However, no published studies of psychotherapeutic treatments
      for anxiety in pregnancy exist. Mindfulness-based cognitive therapy (MBCT) may
      substantially reduce anxiety and co-morbid symptoms in people with anxiety
      disorders. Coping with Anxiety through Living Mindfully (CALM) Pregnancy is an
      adaptation of MBCT designed to address anxiety in pregnant women. This study
      examined the feasibility, acceptability, and clinical outcomes of the CALM
      Pregnancy intervention in pregnant women anxiety. Twenty-four pregnant women with
      generalized anxiety disorder (GAD) or prominent symptoms of generalized anxiety
      participated in an open treatment trial of the CALM Pregnancy group intervention.
      Psychiatric diagnoses were determined by structured clinical interview, and self
      report measures of anxiety, worry, depression, self-compassion, and mindfulness
      were completed at baseline and post-intervention. Qualitative feedback was
      elicited via questionnaire. Twenty-three participants completed the intervention
      with high attendance and good compliance with home practice. Completers showed
      statistically and clinically significant improvements in anxiety, worry, and
      depression, and significant increases in self-compassion and mindfulness. Of the
      17 participants who met GAD criteria at baseline, only one continued to meet
      criteria post-intervention. Participants regarded their experience in the
      intervention to be overwhelmingly positive. MBCT in the form of the CALM
      Pregnancy intervention holds potential to provide effective, non-pharmacological
      treatment for pregnant women with anxiety. These promising findings warrant
      further testing of the intervention with a randomized controlled trial. 

PMID- 24449193
TI  - Assessment of the usefulness of magnetic resonance brain imaging in patients
      presenting with acute seizures.
AB  - BACKGROUND: Magnetic Resonance Imaging (MRI) is increasingly available as a tool
      for assessment of patients presenting to acute services with seizures. AIMS: We
      set out to prospectively determine the usefulness of early MRI brain in a cohort
      of patients presenting with acute seizures. METHODS: We examined the MR imaging
      studies performed in patients admitted solely because of acute seizures to Cork
      University Hospital over a 12-month period. The main aim of the study was to
      determine if the MRI established the proximate cause for the patient's recent
      seizure. We identified 91 patients who underwent MRI brain within 48 h of
      admission for seizures. RESULTS: Of the 91 studies, 51 were normal (56 %). The
      remaining 40 studies were abnormal as follows: microvascular disease (usually
      moderate/severe) (n = 19), post-traumatic gliosis (n = 7), remote symptomatic
      lesion (n = 6), primary brain tumour (n = 5), venous sinus thrombosis (n = 3),
      developmental lesion (n = 3), post-surgical gliosis (n = 3) and single cases of
      demyelination, unilateral hippocampal sclerosis, lobar haemorrhage and metastatic
      malignant melanoma. Abnormalities in diffusion-weighted sequences that were
      attributable to prolonged ictal activity were seen in nine patients, all of who
      had significant ongoing clinical deficits, most commonly delirium. Of the 40
      patients with abnormal MRI studies, seven patients had unremarkable CT brain. MR
      brain imaging revealed the underlying cause for acute seizures in 44 % of
      patients. CT brain imaging failed to detect the cause of the acute seizures in 19
      % of patients in whom subsequent MRI established the cause. CONCLUSION: This
      study emphasises the importance of obtaining optimal imaging in people admitted
      with acute seizures.

PMID- 24449194
TI  - Prognostic significance of lymph node status in patients with metastatic
      colorectal carcinoma treated with lymphadenectomy.
AB  - BACKGROUND AND OBJECTIVES: To test prognostic significance of lymph node status
      in patients with metastatic colorectal carcinoma (mCRC). METHODS: Four hundred
      ninety six patients diagnosed with synchronous mCRC and treated with
      lymphadenectomy between 1995 and 2008 were identified and divided into groups
      pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2
      group) according to their lymph node status. The Kaplan-Meier and Cox regression
      analyses were used to test associations and independent predictor status of lymph
      node involvement. RESULTS: The Cox proportional hazards regression showed pN as
      significantly associated with disease-specific survival (DSS) both in univariate
      (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95%
      CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan-Meier analysis demonstrated
      that patients with pN2 and pN1 had a significantly worse DSS compared with
      patients with pN0 tumors (respectively, 17.273 +/- 1.020 and 27.145 +/- 1.715 vs.
      34.992 +/- 2.143 months; P < 0.001). In accuracy analyses based on AUC values,
      nodal status demonstrated the highest accuracy (65.1%) out of all the variables.
      CONCLUSIONS: Our findings indicate that optimal TNM staging for mCRC should
      incorporate lymph node status to provide a more effective and predictive model.

PMID- 24449195
TI  - Telomeric attrition with age and temperature in Eastern mosquitofish (Gambusia
      holbrooki).
AB  - Telomeric attrition has repeatedly been found to correlate with the ageing of
      organisms; however, recent research is increasingly showing that the determinants
      of attrition dynamics are not well understood. This study examined the relative
      telomere lengths in Eastern mosquitofish, Gambusia holbrooki, kept at different
      temperatures and at different ages. Newly born fry were randomly selected for one
      of four treatment groups: 20, 30, 20-30, and 30-20  degrees C, where the third
      and fourth treatment groups were gradually changed from their starting
      temperature to their final temperature between days 10 and 14. Telomere length
      was measured, and it was found that length decreased with age and that fish
      exposed to the 20  degrees C treatment had significantly shorter telomeres than
      those that received the 30-20  degrees C treatment. Telomeric attrition with age
      agrees with results previously found in studies of telomeres; however, the
      variation in attrition with temperature was not simply predictable and may be the
      synergistic effects of temperature and some other factor.

PMID- 24449196
TI  - Moisture-activated torsional graphene-fiber motor.
AB  - A new type of moisture-driven rotational motor is developed using a helical
      arrangement of graphene sheets along a graphene oxide fiber, which not only
      presents remarkable performance as a reversible rotary motor with a rotary speed
      of up to about 5200 revolutions per minute under humidity alternation, but also
      allows the construction of humidity switches and promising moisture-triggered
      electric generators. 

PMID- 24449198
TI  - Crystal structure determination of anti-DNA Fab A52.
AB  - A52 is a murine monoclonal antibody isolated from autoimmune New Zealand
      Black/New Zealand White F1 mice that recognizes single and double stranded DNA.
      This mouse strain spontaneously develops systemic lupus erythematosus-like
      symptoms and has served as a model for that disease for many years. The 1.62 A
      crystal structure of the A52 Fab fragment reveals an H3 complementarity
      determining region with four closely spaced arginine residues, creating a
      positively charged surface to accommodate bound DNA.

PMID- 24449199
TI  - WNT10A mutations account for 1/4 of population-based isolated oligodontia and
      show phenotypic correlations.
AB  - A large proportion (>50%) of patients with isolated oligodontia were recently
      reported with WNT10A mutations. We have analyzed a population-based cohort of 102
      individuals diagnosed with non-syndromic oligodontia and a mean of 8.2 missing
      teeth. The cohort included 94 families and screening of WNT10A identified that 26
      probands (27.7%) had at least one WNT10A variant. When we included the MSX1,
      PAX9, AXIN2, EDA, EDAR, and EDARADD genes, 38.3% of probands were positive for a
      mutation. Biallelic WNT10A mutations were strongly associated with a larger
      number of missing teeth (11.09) when compared to both monoallelic WNT10 mutations
      (6.82) and the group without mutations in WNT10A, MSX1, PAX9, AXIN2, EDA, EDAR,
      or EDARADD (7.77). Genotype-phenotype analysis of individuals with WNT10A
      mutations showed that premolars were the most common missing teeth. Furthermore,
      biallelic WNT10A mutations were associated with absence of maxillary and
      mandibular molars as well as mandibular central incisors. Maxillary central
      incisors were always present. Thus, our study indicates that WNT10A mutations are
      associated with both the type and numbers of missing teeth. Furthermore, we show
      that this population-based cohort of isolated oligodontia had a considerably
      lower frequency of mutated WNT10A alleles and a lower mean number of missing
      teeth when compared to patients recruited from dental specialist centers.

PMID- 24449200
TI  - 1p34.3 deletion involving GRIK3: Further clinical implication of GRIK family
      glutamate receptors in the pathogenesis of developmental delay.
AB  - A growing body of evidence suggests an association between
      microdeletion/microduplication and schizophrenia/intellectual disability.
      Abnormal neurogenesis and neurotransmission have been implicated in the
      pathogenesis of these neuropsychiatric and neurodevelopmental disorders. The
      kainate/AMPA-type ionotropic glutamate receptor (GRIK = glutamate receptor,
      ionotropic, kainate) plays a critical role in synaptic potentiation, which is an
      essential process for learning and memory. Among the five known GRIK family
      members, haploinsufficiency of GRIK1, GRIK2, and GRIK4 are known to cause
      developmental delay, whereas the roles of GRIK3 and GRIK5 remain unknown. Herein,
      we report on a girl who presented with a severe developmental delay predominantly
      affecting her language and fine motor skills. She had a 2.6-Mb microdeletion in
      1p34.3 involving GRIK3, which encodes a principal subunit of the kainate-type
      ionotropic glutamate receptor. Given its strong expression pattern in the central
      nervous system and the biological function of GRIK3 in presynaptic
      neurotransmission, the haploinsufficiency of GRIK3 is likely to be responsible
      for the severe developmental delay in the proposita. A review of genetic
      alterations and the phenotypic effects of all the GRIK family members support
      this hypothesis. The current observation of a microdeletion involving GRIK3, a
      kainate-type ionotropic glutamate receptor subunit, and the neurodevelopmental
      manifestation in the absence of major dysmorphism provides further clinical
      implication of the possible role of GRIK family glutamate receptors in the
      pathogenesis of developmental delay.

PMID- 24449202
TI  - Patients and families generally welcome secondary genomic findings: support for
      return of incidental findings may encourage shift toward predictive genetic
      testing.

PMID- 24449201
TI  - Newly described clinical features in two siblings with MACS syndrome and a novel
      mutation in RIN2.
AB  - The disorder comprising Macrocephaly, Alopecia, Cutis laxa, and Scoliosis has
      been designated MACS syndrome. It is a rare condition, inherited in an autosomal
      recessive pattern. Three families from different ethnic origins have so far been
      reported and were all linked to homozygous mutations in RIN2, a gene encoding the
      Ras and Rab interactor 2 protein involved in cell trafficking. We describe herein
      the fourth family with MACS syndrome in two siblings carrying a novel homozygous
      mutation, c.1878_1879insC in exon 8 of the RIN2 gene, which predicts
      p.Ile627Hisfs*7. We also report on additional findings not previously described
      in MACS syndrome, including bronchiectasis and hypergonadotropic hypogonadism.
      Finally, our overall data support the argument that RIN2 syndrome is a more
      appropriate name for the disorder.

PMID- 24449203
TI  - Court ruling invalidates patent on noninvasive test for down syndrome: decision
      cites landmark Supreme Court ruling in Myriad Genetics case.

PMID- 24449205
TI  - Parenthood in migration: how to face vulnerability.
AB  - Whether they are African or Asian, the children of immigrant families live in
      situations in which they may be exposed to serious trauma. Immigrant families
      themselves often live in extreme conditions. Although research has described
      these conditions, intervention is still inadequate. These families need not only
      medical or psychological treatment but also basic needs for survival such as
      food, shelter, a place to sleep, a place to bury their dead. However, the
      psychological care of immigrant children and their families has much to teach us.
      We set out here to share what we have learned about immigrant families with
      infants. 

PMID- 24449206
TI  - p107 is a crucial regulator for determining the adipocyte lineage fate choices of
      stem cells.
AB  - Thermogenic (beige and brown) adipocytes protect animals against obesity and
      metabolic disease. However, little is known about the mechanisms that commit stem
      cells toward different adipocyte lineages. We show here that p107 is a master
      regulator of adipocyte lineage fates, its suppression required for commitment of
      stem cells to the brown-type fate. p107 is strictly expressed in the stem cell
      compartment of white adipose tissue depots and completely absent in brown adipose
      tissue. Remarkably, p107-deficient stem cells uniformly give rise to brown-type
      adipocytes in vitro and in vivo. Furthermore, brown fat programming of
      mesenchymal stem cells by PRDM-BF1-RIZ1 homologous domain containing 16 (Prdm16)
      was associated with a dramatic reduction of p107 levels. Indeed, Prdm16 directly
      suppressed p107 transcription via promoter binding. Notably, the sustained
      expression of p107 blocked the ability of Prdm16 to induce brown fat genes. These
      findings demonstrate that p107 expression in stem cells commits cells to the
      white versus brown adipose lineage.

PMID- 24449207
TI  - Biochemical characterization of prostate-specific membrane antigen from canine
      prostate carcinoma cells.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA) remains an important target
      for diagnostic and therapeutic application for human prostate cancer. Model cell
      lines have been recently developed to study canine prostate cancer but their PSMA
      expression and enzymatic activity have not been elucidated. The present study was
      focused on determining PSMA expression in these model canine cell lines and the
      use of fluorescent small-molecule enzyme inhibitors to detect canine PSMA
      expression by flow cytometry. METHODS: Western blot and RT-PCR were used to
      determine the transcriptional and translational expression of PSMA on the canine
      cell lines Leo and Ace-1. An endpoint HPLC-based assay was used to monitor the
      enzymatic activity of canine PSMA and the potency of enzyme inhibitors. Flow
      cytometry was used to detect the PSMA expressed on Leo and Ace-1 cells using a
      fluorescently tagged PSMA enzyme inhibitor. RESULTS: Canine PSMA expression on
      the Leo cell line was confirmed by Western blot and RT-PCR, the enzyme activity,
      and flow cytometry. Kinetic parameters Km and Vmax of PSMA enzymatic activity for
      the synthetic substrate (PABGgammaG) were determined to be 393 nM and 220 pmol
      min(-1)  mg protein(-1) , respectively. The inhibitor core 1 and fluorescent
      inhibitor 2 were found to be potent reversible inhibitors (IC50  = 13.2 and 1.6
      nM, respectively) of PSMA expressed on the Leo cell line. Fluorescent labeling of
      Leo cells demonstrated that the fluorescent PSMA inhibitor 2 can be used for the
      detection of PSMA-positive canine prostate tumor cells. Expression of PSMA on Ace
      1 was low and not detectable by flow cytometry. CONCLUSIONS: The results
      described herein have demonstrated that PSMA is expressed on canine prostate
      tumor cells and exhibits similar enzymatic characteristics as human PSMA. The
      findings show that the small molecule enzyme inhibitors currently being studied
      for use in diagnosis and therapy of human prostate cancer can also be extended to
      include canine prostate cancer. Importantly, the findings demonstrate that the
      potential of the inhibitors for use in diagnosis and therapy can be evaluated in
      an immunocompetent animal model that naturally develops prostate cancer before
      use in humans.

PMID- 24449208
TI  - Osteolytic femoral lesion detected by sonography in a case of light chain
      deposition disease.
AB  - We describe a case of light chain deposition disease presenting as worsening of
      renal failure with a lytic femoral bone lesion discovered by sonography. Although
      sonography cannot be considered to be the test of choice in evaluating multiple
      myeloma, this technique may allow the detection and the biopsy of osteolytic bone
      lesions, particularly in accessible locations. Differential diagnosis is
      discussed.

PMID- 24449209
TI  - B-cell receptors expressed by lymphomas of hepatitis C virus (HCV)-infected
      patients rarely react with the viral proteins.
AB  - Chronic hepatitis C virus (HCV) infection has been implicated in the induction
      and maintenance of B-cell lymphomas. The strongest evidence for this derives from
      clinical observations of tumor regressions upon antiviral treatments. Here we
      used multiple methods to test the hypothesis that the expansion of HCV-specific B
      cells gives rise to lymphomas. We obtained lymphoma tissues from HCV-infected
      lymphoma patients, including some that later regressed upon antiviral treatments.
      We expressed the lymphoma B-cell receptors as soluble immunoglobulin Gs and
      membrane IgMs, and analyzed their reactivity with HCV proteins and with HCV
      virions. We confirmed previous reports that HCV-associated lymphomas use a
      restricted immunoglobulin variable region gene repertoire. However, we found no
      evidence for their binding to the HCV antigens. We conclude that most lymphomas
      of HCV-infected patients do not arise from B cells aimed at eliminating the
      virus. 

PMID- 24449210
TI  - Inherited genetic susceptibility to monoclonal gammopathy of unknown
      significance.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is present in ~2% of
      individuals age >50 years. The increased risk of multiple myeloma (MM) in
      relatives of individuals with MGUS is consistent with MGUS being a marker of
      inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms
      (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33
      (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have
      recently been shown to influence MM risk. To examine the impact of these 7 SNPs
      on MGUS, we analyzed two case-control series totaling 492 cases and 7306
      controls. Each SNP independently influenced MGUS risk with statistically
      significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and
      rs4273077. SNP associations were independent, with risk increasing with a larger
      number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)).
      Collectively these data are consistent with a polygenic model of disease
      susceptibility to MGUS. 

PMID- 24449211
TI  - A prospective study on drug monitoring of PEGasparaginase and Erwinia
      asparaginase and asparaginase antibodies in pediatric acute lymphoblastic
      leukemia.
AB  - This study prospectively analyzed the efficacy of very prolonged courses of
      pegylated Escherichia coli asparaginase (PEGasparaginase) and Erwinia
      asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. Patients
      received 15 PEGasparaginase infusions (2500 IU/m(2) every 2 weeks) in
      intensification after receiving native E coli asparaginase in induction. In case
      of allergy to or silent inactivation of PEGasparaginase, Erwinia asparaginase (20
      000 IU/m(2) 2-3 times weekly) was given. Eighty-nine patients were enrolled in
      the PEGasparaginase study. Twenty (22%) of the PEGasparaginase-treated patients
      developed an allergy; 7 (8%) showed silent inactivation. The PEGasparaginase
      level was 0 in all allergic patients (grade 1-4). Patients without
      hypersensitivity to PEGasparaginase had serum mean trough levels of 899 U/L.
      Fifty-nine patients were included in the Erwinia asparaginase study; 2 (3%)
      developed an allergy and none silent inactivation. Ninety-six percent had at
      least 1 trough level >=100 U/L. The serum asparagine level was not always
      completely depleted with Erwinia asparaginase in contrast to PEGasparaginase. The
      presence of asparaginase antibodies was related to allergies and silent
      inactivation, but with low specificity (64%). Use of native E coli asparaginase
      in induction leads to high hypersensitivity rates to PEGasparaginase in
      intensification. Therefore, PEGasparaginase should be used upfront in induction,
      and we suggest that the dose could be lowered. Switching to Erwinia asparaginase
      leads to effective asparaginase levels in most patients. Therapeutic drug
      monitoring has been added to our ALL-11 protocol to individualize asparaginase
      therapy. 

PMID- 24449212
TI  - Immune evasion by oncogenic proteins of acute myeloid leukemia.
AB  - PML-RARA and AML1-ETO are important oncogenic fusion proteins that play a central
      role in transformation to acute myeloid leukemia (AML). Whether these fusion
      proteins render the tumor cells with immune evasion properties is unknown. Here
      we show that both oncogenic proteins specifically downregulate the expression of
      CD48, a ligand of the natural killer (NK) cell activating receptor 2B4, thereby
      leading to decreased killing by NK cells. We demonstrate that this process is
      histone deacetylase (HDAC)-dependent, that it is mediated through the
      downregulation of CD48 messenger RNA, and that treatment with HDAC inhibitors
      (HDACi) restores the expression of CD48. Furthermore, by using chromatin
      immunoprecepitation (ChIP) experiments, we show that AML1-ETO directly interacts
      with CD48. Finally, we show that AML patients who are carrying these specific
      translocations have low expression of CD48.

PMID- 24449213
TI  - Differential contribution of FXa and thrombin to vascular inflammation in a mouse
      model of sickle cell disease.
AB  - Activation of coagulation and vascular inflammation are prominent features of
      sickle cell disease (SCD). Previously, we have shown that inhibition of tissue
      factor (TF) attenuates activation of coagulation and vascular inflammation in
      mouse models of SCD. In this study, we examined the mechanism by which
      coagulation proteases enhance vascular inflammation in sickle BERK mice. To
      specifically investigate the contribution of FXa and thrombin, mice were fed chow
      containing either rivaroxaban or dabigatran, respectively. In addition, we used
      bone marrow transplantation to generate sickle mice deficient in either protease
      activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) on
      nonhematopoietic cells. FXa inhibition and PAR-2 deficiency in nonhematopoietic
      cells attenuated systemic inflammation, measured by plasma levels of interleukin
      6 (IL-6). In contrast, neither thrombin inhibition nor PAR-1 deficiency in
      nonhematopoietic cells affected plasma levels of IL-6 in sickle mice. However,
      thrombin did contribute to neutrophil infiltration in the lung, independently of
      PAR-1 expressed by nonhematopoietic cells. Furthermore, the TF-dependent increase
      in plasma levels of soluble vascular cell adhesion molecule-1 in sickle mice was
      not mediated by FXa or thrombin. Our data indicate that TF, FXa, and thrombin
      differentially contribute to vascular inflammation in a mouse model of SCD. 

PMID- 24449214
TI  - SET-NUP214 is a recurrent gammadelta lineage-specific fusion transcript
      associated with corticosteroid/chemotherapy resistance in adult T-ALL.
AB  - The SET-NUP214 (TAF1/CAN) fusion gene is a rare genetic event in T-cell acute
      lymphoblastic leukemia (T-ALL). Eleven (6%) of 196 T-ALL patients enrolled in the
      French Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) 2003 and
      2005 trials harbored a SET-NUP214 transcript. SET-NUP214-positive patients were
      predominantly (10 [91%] of 11) T-cell receptor (TCR)-negative and strikingly
      associated with TCRgammadelta lineage T-ALLs, as defined by expression of
      TCRgammadelta, TCRdelta and/or TCRgamma rearrangements but no complete TCRbeta
      variable diversity joining rearrangement in surface CD3/TCR-negative cases. When
      compared with SET-NUP214-negative patients, SET-NUP214-positive patients showed a
      significantly higher rate of corticosteroid resistance (91% vs 44%; P = .003) and
      chemotherapy resistance (100% vs 44%; P = .0001). All SET-NUP214-positive
      patients but one achieved complete remission, and 9 were allografted. Despite the
      poor early-treatment sensitivity, the outcome of SET-NUP214-positive patients was
      similar to that of SET-NUP214-negative patients. 

PMID- 24449216
TI  - Tryptophan and inhibitors of tryptophan 2,3-dioxygenase as antidepressants.

PMID- 24449215
TI  - Downregulation of RUNX1/CBFbeta by MLL fusion proteins enhances hematopoietic
      stem cell self-renewal.
AB  - RUNX1/CBFbeta (core binding factor [CBF]) is a heterodimeric transcription factor
      complex that is frequently involved in chromosomal translocations, point
      mutations, or deletions in acute leukemia. The mixed lineage leukemia (MLL) gene
      is also frequently involved in chromosomal translocations or partial tandem
      duplication in acute leukemia. The MLL protein interacts with RUNX1 and prevents
      RUNX1 from ubiquitin-mediated degradation. RUNX1/CBFbeta recruits MLL to regulate
      downstream target genes. However, the functional consequence of MLL fusions on
      RUNX1/CBFbeta activity has not been fully understood. In this report, we show
      that MLL fusion proteins and the N-terminal MLL portion of MLL fusions
      downregulate RUNX1 and CBFbeta protein expression via the MLL CXXC domain and
      flanking regions. We confirmed this finding in Mll-Af9 knock-in mice and human
      M4/M5 acute myeloid leukemia (AML) cell lines, with or without MLL
      translocations, showing that MLL translocations cause a hypomorph phenotype of
      RUNX1/CBFbeta. Overexpression of RUNX1 inhibits the development of AML in Mll-Af9
      knock-in mice; conversely, further reducing Runx1/Cbfbeta levels accelerates MLL
      AF9-mediated AML in bone marrow transplantation assays. These data reveal a newly
      defined negative regulation of RUNX1/CBFbeta by MLL fusion proteins and suggest
      that targeting RUNX1/CBFbeta levels may be a potential therapy for MLLs. 

PMID- 24449217
TI  - Tryptophan and inhibitors of tryptophan 2,3-dioxygenase as antidepressants:
      reply.

PMID- 24449218
TI  - SSRIs probably counteract premenstrual syndrome by inhibiting the serotonin
      transporter.

PMID- 24449219
TI  - Response from Thelma Lovick.

PMID- 24449220
TI  - The Pauson-Khand mechanism revisited: origin of CO in the final product.
AB  - The mechanism of the Pauson-Khand reaction has been studied by mass spectrometry
      and it has been found, through ion-molecule reaction with (13) CO, that the
      carbon monoxide incorporated into the product cyclopentenone is one that has been
      retained within the complex. Theoretical and kinetic calculations support this
      finding, which provides a complementary explanation for the effect of Pauson
      Khand promoters. 

PMID- 24449221
TI  - Microbiopsies versus Bergstrom needle for skeletal muscle sampling: impact on
      maximal mitochondrial respiration rate.
AB  - INTRODUCTION: Microbiopsies are increasingly used as an alternative to the
      standard Bergstrom technique for skeletal muscle sampling. The potential impact
      of these two different procedures on mitochondrial respiration rate is unknown.
      The objective of this work was to compare microbiopsies versus Bergstrom
      procedure on mitochondrial respiration in skeletal muscle. METHODS: 52 vastus
      lateralis muscle samples were obtained from 13 anesthetized pigs, either with a
      Bergstrom [6 gauges (G)] needle or with microbiopsy needles (12, 14, 18G).
      Maximal mitochondrial respiration (V GM-ADP) was assessed using an oxygraphic
      method on permeabilized fibers. RESULTS: The weight of the muscle samples and V
      GM-ADP decreased with the increasing gauge of the needles. A positive nonlinear
      relationship was observed between the weight of the muscle sample and the level
      of maximal mitochondrial respiration (r = 0.99, p < 0.05) and between needle size
      and maximal mitochondrial respiration (r = 0.99, p < 0.05). CONCLUSION:
      Microbiopsies give lower muscle sample weight and maximal rate of mitochondrial
      respiration compared to the standard Bergstrom needle.Therefore, the higher the
      gauge (i.e. the smaller the size) of the microbiopsy needle, the lower is the
      maximal rate of respiration. Microbiopsies of skeletal muscle underestimate the
      maximal mitochondrial respiration rate, and this finding needs to be highlighted
      for adequate interpretation and comparison with literature data.

PMID- 24449222
TI  - Galvanic vestibular stimulation impairs cell proliferation and neurogenesis in
      the rat hippocampus but not spatial memory.
AB  - Galvanic vestibular stimulation (GVS) is a method of activating the peripheral
      vestibular system using direct current that is widely employed in clinical
      neurological testing. Since movement is recognized to stimulate hippocampal
      neurogenesis and movement is impossible without activation of the vestibular
      system, we speculated that activating the vestibular system in rats while
      minimizing movement, by delivering GVS under anesthesia, would affect hippocampal
      cell proliferation and neurogenesis, and spatial memory. Compared with the sham
      control group, the number of cells incorporating the DNA replication marker,
      bromodeoxyuridine (BrdU), was significantly reduced in the bilateral hippocampi
      in both the cathode left-anode right and cathode right-anode left stimulation
      groups (P <= 0.0001). The majority of the BrdU(+ve) cells co-expressed Ki-67, a
      marker for the S phase of the cell cycle, suggesting that these BrdU(+ve) cells
      were still in the cell cycle; however, there was no significant difference in the
      degree of co-labeling between the two stimulation groups. Single labeling for
      doublecortin (DCX), a marker of immature neurons, showed that while there was no
      significant difference between the different groups in the number of DCX(+ve)
      cells in the right dentate gryus, in the left dentate gyrus there was a
      significant decrease in the cathode left-anode right group compared with the sham
      controls (P <= 0.03). Nonetheless, when animals were tested in place recognition,
      object exploration and Morris water maze tasks, there were no significant
      differences between the GVS groups and the sham controls. These results suggest
      that GVS can have striking effects on cell proliferation and possibly
      neurogenesis in the hippocampus, without affecting spatial memory.

PMID- 24449223
TI  - The Psychiatry OSCE: a 20-year retrospective.
AB  - OBJECTIVE: Twenty years ago researchers at the University of Toronto launched the
      Psychiatry Skills Assessment Project (PSAP), a research program exploring
      Objective Structured Clinical Examinations (OSCEs) in psychiatry. Between 1994
      and 2005 PSAP produced publications on the feasibility, reliability, validity,
      ethics, and practical concerns of OSCEs in psychiatry. The current review has two
      parts: a review of the state of the art of OSCEs in psychiatry 20 years after
      they were introduced and documentation of the impact of the PSAP research
      program. METHODS: A literature search identified all publications on OSCEs and
      psychiatry. Articles were coded thematically, and locations of agreement and
      controversies were identified. Bibliometric analysis identified citations of PSAP
      research papers, which were analyzed thematically. RESULTS: As of May 2013, there
      were 250 publications related to OSCEs in psychiatry (not including 10 PSAP
      papers), published in 29 different countries and ten languages. Prominent topics
      were the validity and acceptability of OSCEs and SPs, systems issues in adopting
      OSCEs in psychiatry, and the effects on learning. Eighty-eight percent of all
      publications cited PSAP work (300 citations). Citations were employed for four
      purposes: as evidence/justification (54 %); to frame replication research (14 %);
      to support adaptation of OSCEs in other countries and professions (15 %); and for
      debate (18 %). CONCLUSIONS: Over the past 20 years, use of OSCEs has grown
      steadily in psychiatry, and several national certification organizations have
      adopted OSCEs. PSAP work, introduced two decades ago, continues to provide a
      scholarly foundation for psychometric, practical, and ethical issues of interest
      to this field.

PMID- 24449224
TI  - Using peer review to improve research and promote collaboration.
AB  - OBJECTIVE: The declining success rate of National Institutes of Health (NIH)
      grant applications highlights the need for interdisciplinary work within a large,
      diverse department to improve chances of federal funding success. The authors
      demonstrate how systematic peer review promotes two goals: enhancing the quality
      of research proposals and cultivating a collaborative departmental culture.
      METHODS: Changes to the Research Review Committee (RRC) in the Department of
      Psychiatry at the University of Pittsburgh were instituted to accommodate the
      increasingly interdisciplinary nature of grant applications, integrate revisions
      to NIH grant application processes, and incorporate advances in computer
      technology. RESULTS: The internal peer review process is associated with success
      in obtaining research support and with significant levels of collaborative
      scientific work reflected in both grant applications and peer-reviewed
      publications. CONCLUSIONS: A rich collaborative environment promoted through a
      rigorous internal peer review system has many benefits for both the quality of
      scholarly work and the collegiality of the research environment.

PMID- 24449225
TI  - Distribution of an allele associated with blond hair color across Northern Island
      Melanesia.
AB  - Pigmentation of the skin, hair, and eyes is a complex trait controlled by
      multiple genetic loci. Recently a non-synonymous mutation in the pigmentation
      candidate gene TYRP1 was shown to be significantly associated with a blond-hair
      phenotype in populations from the Solomon Islands. The distribution of this
      mutation in the islands of Northern Island Melanesia, where the blondism
      phenotype is also prevalent, was unknown. Here, we present data describing the
      distribution of this allele in 550 individuals sampled from across this region,
      and test for associations between genotype at this locus and quantitatively
      measured skin and hair pigmentation phenotype. We report that the frequency of
      the 93C allele is notably lower than observed in the Solomons (0.12 vs. 0.26).
      The allele exhibits significant geographic heterogeneity across the islands
      sampled (chi(2)  = 108.4, P < 0.0001). It is observed at its highest frequencies
      on the islands of New Ireland and New Hanover, while being almost completely
      absent from the large island of New Britain. Using linear regression with age,
      sex, and island as covariates we report that, as in the Solomons, the 93C allele
      is significantly associated with a decrease in hair pigmentation but not skin
      pigmentation. We discuss the distribution of the 93C allele across the Southwest
      Pacific in light of its possible place of origin and dispersal.

PMID- 24449226
TI  - Practical considerations in gene therapy for HIV cure.
AB  - Despite the success of antiretroviral therapy in suppressing HIV-1 replication
      and extending the life of HIV-1 infected individuals, this regimen is associated
      with risks for non-AIDS morbidity and mortality, requires life commitment, and
      has a high cost. In this context, gene therapy approaches that have the potential
      to cure HIV-1 infection present a clear option for eradication of the virus in
      the next decades. Gene therapy must overcome concerns related to its
      applicability to HIV-1 infection, the safety of cytotoxic conditioning required
      for cell-based approaches, clinical trial design, selection of gene-modified
      cells, and the restrictive cost of manufacturing and technology. These concerns
      are discussed herein in the context of the most relevant gene therapy studies
      conducted so far in HIV/AIDS. 

PMID- 24449227
TI  - Association of peripheral neuropathy with circulating advanced glycation end
      products, soluble receptor for advanced glycation end products and other risk
      factors in patients with type 2 diabetes.
AB  - BACKGROUND: The pathogenesis of diabetic peripheral neuropathy remains uncertain
      and nonenzymatic glycoxidation is one of the contributing mechanisms. The aim of
      this study was to assess the respective relationship of diabetic peripheral
      neuropathy with glycoxidation, compared with other identified risk factors, in
      patients with type 2 diabetes. METHODS: We included 198 patients with type 2
      diabetes and high risk for vascular complications. Circulating concentrations of
      three advanced glycation end products (carboxymethyllysine, methyl-glyoxal
      hydroimidazolone-1, pentosidine) and of their soluble receptor (sRAGE) were
      measured. Peripheral neuropathy was assessed by the neuropathy disability score
      and by the monofilament test and defined as either an abnormal monofilament test
      and/or a neuropathy disability score >=6. Multivariate regression analyses were
      performed adjusting for potential confounding factors for neuropathy: age,
      gender, diabetes duration, current smoking, systolic blood pressure, waist
      circumference, height, peripheral arterial occlusive disease, glycated
      haemoglobin, estimated glomerular filtration rate and lipid profile. RESULTS:
      Prevalence of peripheral neuropathy was 20.7%. sRAGE and carboxymethyllysine were
      independently and positively associated with the presence of peripheral
      neuropathy. No significant association was found between peripheral neuropathy
      and methyl-glyoxal-hydroimidazolone-1 or pentosidine. Waist circumference, height
      and peripheral arterial occlusive disease were independently associated with
      peripheral neuropathy. CONCLUSIONS: Carboxymethyllysine and sRAGE were
      independently associated with peripheral neuropathy in patients with type 2
      diabetes. Although the conclusions are limited by the absence of a healthy
      control population, this study confirms the relationship between advanced
      glycoxidation and diabetic peripheral neuropathy, independently of other risk
      factors.

PMID- 24449228
TI  - Effect of nonsurgical periodontal therapy (with or without oral doxycycline
      delivery) on glycemic status and clinical periodontal parameters in patients with
      prediabetes: a short-term longitudinal randomized case-control study.
AB  - OBJECTIVE: The aim of the present short-term longitudinal randomized case-control
      study was to assess the effect of nonsurgical periodontal therapy (NSPT) (with
      and without oral doxycycline delivery) on glycemic status and clinical
      periodontal parameters in patients with prediabetes. MATERIAL AND METHODS: Sixty
      six patients with prediabetes and periodontal disease were included.
      Characteristics of the study cohort (age, gender, socioeconomic status [SES]
      education status, duration of prediabetes, and type of treatment adopted for
      prediabetes management) were recorded. Patients were randomly divided into two
      groups (33 patients/group). In group 1, scaling and root planing (SRP) was
      performed, and in group-2, patients underwent SRP and oral doxycycline (100 mg)
      administration once daily for 15 days. In each group, the following parameters
      were investigated at baseline and after 3 months: (a) fasting blood glucose level
      (FBGL), (b) hemoglobin A1c (HbA1c), and (c) periodontal parameters (plaque index
      [PI], bleeding on probing [BOP], probing depth [PD], and clinical attachment loss
      [AL]). Statistical analysis was performed using Student's t test. RESULTS: There
      was no significant difference in age, gender, SES, education status, and duration
      and treatment of prediabetes among individuals in groups 1 and 2. Three months
      post-NSPT, FBGL and HbA1c were significantly reduced among patients in group 1 (P
      < 0.05) and group 2 (P < 0.05) compared to baseline. Three months post-NSPT, PI
      (P < 0.05), BOP (P < 0.05), and PD (P < 0.05) were significantly reduced among
      patients in group 1 (P < 0.05) and group 2 (P < 0.05) compared to baseline. There
      was no difference in clinical AL between the groups after 3 months of NSPT.
      CONCLUSION: NSPT (with and without oral doxycycline delivery) reduces
      hyperglycemia and periodontal inflammation in patients with prediabetes.

PMID- 24449229
TI  - Telehealth personalized cancer risk communication to motivate colonoscopy in
      relatives of patients with colorectal cancer: the family CARE Randomized
      controlled trial.
AB  - PURPOSE: The rate of adherence to regular colonoscopy screening in individuals at
      increased familial risk of colorectal cancer (CRC) is suboptimal, especially
      among rural and other geographically underserved populations. Remote
      interventions may overcome geographic and system-level barriers. We compared the
      efficacy of a telehealth-based personalized risk assessment and communication
      intervention with a mailed educational brochure for improving colonoscopy
      screening among at-risk relatives of patients with CRC. METHODS: Eligible
      individuals age 30 to 74 years who were not up-to-date with risk-appropriate
      screening and were not candidates for genetic testing were recruited after
      contacting patients with CRC or their next of kin in five states. Enrollees were
      randomly assigned as family units to either an active, personalized intervention
      that incorporated evidence-based risk communication and behavior change
      techniques, or a mailed educational brochure. The primary outcome was medically
      verified colonoscopy within 9 months of the intervention. RESULTS: Of the 481
      eligible and randomly assigned at-risk relatives, 79.8% completed the outcome
      assessments within 9 months; 35.4% of those in the personalized intervention
      group and 15.7% of those in the comparison group obtained a colonoscopy. In an
      intent-to-treat analysis, the telehealth group was almost three times as likely
      to get screened as the low-intensity comparison group (odds ratio, 2.83; 95% CI,
      1.87 to 4.28; P < .001). Persons residing in rural areas and those with lower
      incomes benefitted at the same level as did urban residents. CONCLUSION: Remote
      personalized interventions that consider family history and incorporate evidence
      based risk communication and behavior change strategies may promote risk
      appropriate screening in close relatives of patients with CRC.

PMID- 24449232
TI  - Is it time to embrace telephone genetic counseling in the oncology setting?

PMID- 24449230
TI  - Posttraumatic stress and psychological growth in children with cancer: has the
      traumatic impact of cancer been overestimated?
AB  - PURPOSE: To examine posttraumatic stress disorder and posttraumatic stress
      symptoms (PTSD/PTSS) in children with cancer using methods that minimize focusing
      effects and allow for direct comparison to peers without a history of cancer.
      PATIENTS AND METHODS: Children with cancer (n = 255) stratified by time since
      diagnosis, and demographically matched peers (n = 101) were assessed for PTSD
      using structured diagnostic interviews by both child and parent reports, and
      survey measures of PTSS and psychological benefit/growth by child report.
      RESULTS: Cancer was identified as a traumatic event by 52.6% of children with
      cancer, declining to 23.8% in those >= 5 years from diagnosis. By diagnostic
      interview, 0.4% of children with cancer met criteria for current PTSD, and 2.8%
      met lifetime criteria by self-report. By parent report, 1.6% of children with
      cancer met current criteria and 5.9% met lifetime criteria for PTSD. These rates
      did not differ from controls (all Ps >.1). PTSS levels were descriptively lower
      in children with cancer but did not differ from controls when all were referring
      to their most traumatic event (P = .067). However, when referring specifically to
      cancer-related events, PTSS in the cancer group were significantly lower than in
      controls (P = .002). In contrast, perceived growth was significantly higher in
      the cancer group when referring to cancer (P < .001). CONCLUSION: These findings
      suggest no evidence of increased PTSD or PTSS in youths with cancer. Although
      childhood cancer remains a significant and challenging event, these findings
      highlight the capacity of children to adjust, and even thrive, in the face of
      such challenge.

PMID- 24449231
TI  - Updated prognostic model for predicting overall survival in first-line
      chemotherapy for patients with metastatic castration-resistant prostate cancer.
AB  - PURPOSE: Prognostic models for overall survival (OS) for patients with metastatic
      castration-resistant prostate cancer (mCRPC) are dated and do not reflect
      significant advances in treatment options available for these patients. This work
      developed and validated an updated prognostic model to predict OS in patients
      receiving first-line chemotherapy. METHODS: Data from a phase III trial of 1,050
      patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401
      [Alliance]). The data were randomly split into training and testing sets. A
      separate phase III trial served as an independent validation set. Adaptive least
      absolute shrinkage and selection operator selected eight factors prognostic for
      OS. A predictive score was computed from the regression coefficients and used to
      classify patients into low- and high-risk groups. The model was assessed for its
      predictive accuracy using the time-dependent area under the curve (tAUC).
      RESULTS: The model included Eastern Cooperative Oncology Group performance
      status, disease site, lactate dehydrogenase, opioid analgesic use, albumin,
      hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values
      in the high- and low-risk groups, respectively, in the testing set were 17 and 30
      months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and
      26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and
      0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively.
      CONCLUSION: An updated prognostic model for OS in patients with mCRPC receiving
      first-line chemotherapy was developed and validated on an external set. This
      model can be used to predict OS, as well as to better select patients to
      participate in trials on the basis of their prognosis.

PMID- 24449233
TI  - Successful treatment with imatinib in a patient with chronic eosinophilic
      leukemia not otherwise specified.

PMID- 24449234
TI  - Know guilt.

PMID- 24449236
TI  - Sorafenib-induced tumor response in a patient with metastatic epithelioid
      angiomyolipoma.

PMID- 24449235
TI  - Randomized noninferiority trial of telephone versus in-person genetic counseling
      for hereditary breast and ovarian cancer.
AB  - PURPOSE: Although guidelines recommend in-person counseling before BRCA1/BRCA2
      gene testing, genetic counseling is increasingly offered by telephone. As genomic
      testing becomes more common, evaluating alternative delivery approaches becomes
      increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic
      counseling was noninferior to in-person delivery. PATIENTS AND METHODS:
      Participants (women age 21 to 85 years who did not have newly diagnosed or
      metastatic cancer and lived within a study site catchment area) were randomly
      assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC
      participants received in-person pre- and post-test counseling; TC participants
      completed all counseling by telephone. Primary outcomes were knowledge,
      satisfaction, decision conflict, distress, and quality of life; secondary
      outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC
      versus UC. RESULTS: TC was noninferior to UC on all primary outcomes. At 2 weeks
      after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61),
      perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d
      = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence
      intervals that did not cross their 1-point noninferiority limits. Decision
      conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6;
      upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit.
      Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test
      uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient.
      CONCLUSION: Genetic counseling can be effectively and efficiently delivered via
      telephone to increase access and decrease costs.

PMID- 24449237
TI  - Testicular cancer and platinum: a double-edged sword.

PMID- 24449239
TI  - Breast cancer occurring in the chest wall: rare presentation of ectopic milk line
      breast cancer.

PMID- 24449238
TI  - Liquid biopsies: genotyping circulating tumor DNA.
AB  - Genotyping tumor tissue in search of somatic genetic alterations for actionable
      information has become routine practice in clinical oncology. Although these
      sequence alterations are highly informative, sampling tumor tissue has
      significant inherent limitations; tumor tissue is a single snapshot in time, is
      subject to selection bias resulting from tumor heterogeneity, and can be
      difficult to obtain. Cell-free fragments of DNA are shed into the bloodstream by
      cells undergoing apoptosis or necrosis, and the load of circulating cell-free DNA
      (cfDNA) correlates with tumor staging and prognosis. Moreover, recent advances in
      the sensitivity and accuracy of DNA analysis have allowed for genotyping of cfDNA
      for somatic genomic alterations found in tumors. The ability to detect and
      quantify tumor mutations has proven effective in tracking tumor dynamics in real
      time as well as serving as a liquid biopsy that can be used for a variety of
      clinical and investigational applications not previously possible.

PMID- 24449240
TI  - Nasopharyngeal Hodgkin lymphoma.

PMID- 24449242
TI  - The perfect arrangement.

PMID- 24449241
TI  - Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with
      bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial
      treatment of multiple myeloma: updated follow-up and improved survival.
AB  - PURPOSE: Bortezomib-melphalan-prednisone (VMP) has improved overall survival in
      multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT)
      induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in
      patients with newly diagnosed multiple myeloma. PATIENTS AND METHODS: We randomly
      assigned 511 patients who were not eligible for transplantation to receive VMPT
      VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP
      (nine 5-week cycles without maintenance). RESULTS: In the initial analysis with a
      median follow-up of 23 months, VMPT-VT improved complete response rate from 24%
      to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with
      VMP. In this analysis, median follow-up was 54 months. The median PFS was
      significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months;
      hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in
      the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5
      year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR,
      0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P =
      .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events
      included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%),
      and cardiologic events (11%). All of these, except for thrombocytopenia, were
      significantly more frequent in the VMPT-VT patients. CONCLUSION: Bortezomib and
      thalidomide significantly improved OS in multiple myeloma patients not eligible
      for transplantation.

PMID- 24449243
TI  - Concomitant cisplatin plus radiotherapy and high-dose-rate brachytherapy versus
      radiotherapy alone for stage IIIB epidermoid cervical cancer: a randomized
      controlled trial.
AB  - PURPOSE: The benefits of chemoradiotherapy (CRT) for cervical cancer compared
      with radiation (RT) alone seem to diminish in later-stage disease. However, these
      modalities have not been directly compared for disease-free interval (DFI) and
      overall survival (OS) of women with stage IIIB cervical cancer. PATIENTS AND
      METHODS: We conducted a randomized controlled clinical trial comparing DFI and OS
      of 147 women with stage IIIB squamous cervical cancer who received either
      cisplatin plus RT (CRT) or RT alone (72 patients in the CRT group and 75 patients
      in the RT-only group). RESULTS: The CRT group had significantly better DFI
      (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; P = .02). However, patients in
      the CRT group did not have significantly better OS than those in the RT-only
      group (HR, 0.67; 95% CI, 0.38 to 1.17; P = .16). Toxicity was graded according to
      criteria of the Radiation Therapy Oncology Group. The organs affected (excluding
      hematologic effects) did not differ significantly between groups. Also, late
      toxicity events and organs affected were not significantly disproportionate
      between the study groups. CONCLUSION: For stage IIIB cervical cancer, the
      addition of cisplatin offers a small but significant benefit in DFI, with
      acceptable toxicity.

PMID- 24449248
TI  - Highly effective antibiofilm coating of silver-polymer nanocomposite on polymeric
      medical devices deposited by one step plasma process.
AB  - Foley's catheters were coated with Silver (Ag), plasma polymerized aniline
      (PPAni) and Ag-PPAni composite by plasma based deposition processes which were
      characterized by XRD, EDX, SEM, and FT-IR spectroscopy and bioassays were
      performed to validate their efficacies to kill planktonic cells as well as to
      remove biofilm. The analyses confirmed the formation of Ag nanoparticles (AgNPs),
      PPAni and Ag-PPAni composite and also corroborated their successful deposition
      over the catheters. Antibacterial assays showed that coated catheters were
      capable of killing planktonic cells of most commonly encountered uropathogens and
      equally capable of eradicating biofilm formation by the uropathogens as evident
      from the reduced cfu/ml. UV-vis spectroscopy results showed that the nanoparticle
      coated catheters were capable of gradual release of AgNPs, killing all planktonic
      cells in solution over the time. Foley's catheters coated with AgNPs and their
      composites by one step plasma process were non-toxic devices capable of killing
      planktonic cells and proficient in eradicating biofilm formation which could be
      used to cutback the likelihood of the catheter related complications.

PMID- 24449250
TI  - Smoke spots: promoting smoking with social media.

PMID- 24449249
TI  - Tobacco industry marketing to low socioeconomic status women in the U.S.A.
AB  - OBJECTIVES: Describe tobacco companies' marketing strategies targeting low
      socioeconomic status (SES) females in the U.S.A. METHODS: Analysis of previously
      secret tobacco industry documents. RESULTS: Tobacco companies focused marketing
      on low SES women starting in the late 1970s, including military wives, low-income
      inner-city minority women, 'discount-susceptible' older female smokers and less
      educated young white women. Strategies included distributing discount coupons
      with food stamps to reach the very poor, discount offers at point-of-sale and via
      direct mail to keep cigarette prices low, developing new brands for low SES
      females and promoting luxury images to low SES African-American women. More
      recently, companies integrated promotional strategies targeting low-income women
      into marketing plans for established brands. CONCLUSIONS: Tobacco companies used
      numerous marketing strategies to reach low SES females in the U.S.A. for at least
      four decades. Strategies to counteract marketing to low SES women could include
      (1) counteracting price discounts and direct mail coupons that reduce the price
      of tobacco products, (2) instituting restrictions on point-of-sale advertising
      and retail display and (3) creating counteradvertising that builds resistance to
      psychosocial targeting of low SES women. To achieve health equity, tobacco
      control efforts are needed to counteract the influence of tobacco industry
      marketing to low-income women.

PMID- 24449244
TI  - Cancer genomics and inherited risk.
AB  - Next-generation sequencing (NGS) has enabled whole-exome and whole-genome
      sequencing of tumors for causative mutations, allowing for more accurate
      targeting of therapies. In the process of sequencing the tumor, comparisons to
      the germline genome may identify variants associated with susceptibility to
      cancer as well as other hereditary diseases. Already, the combination of
      massively parallel sequencing and selective capture approaches has facilitated
      efficient simultaneous genetic analysis (multiplex testing) of large numbers of
      candidate genes. As the field of oncology incorporates NGS approaches into tumor
      and germline analyses, it has become clear that the ability to achieve high
      throughput genotyping surpasses our current ability to interpret and
      appropriately apply the vast amounts of data generated from such technologies. A
      review of the current state of knowledge of rare and common genetic variants
      associated with cancer risk or treatment outcome reveals significant progress, as
      well as a number of challenges associated with the clinical translation of these
      discoveries. The combined efforts of oncologists, genetic counselors, and cancer
      geneticists will be required to drive the paradigm shift toward personalized or
      precision medicine and to ensure the incorporation of NGS technologies into the
      practice of preventive oncology. 

PMID- 24449251
TI  - On deciding to have a lobotomy: either lobotomies were justified or decisions
      under risk should not always seek to maximise expected utility.
AB  - In the 1940s and 1950s thousands of lobotomies were performed on people with
      mental disorders. These operations were known to be dangerous, but thought to
      offer great hope. Nowadays, the lobotomies of the 1940s and 1950s are widely
      condemned. The consensus is that the practitioners who employed them were, at
      best, misguided enthusiasts, or, at worst, evil. In this paper I employ standard
      decision theory to understand and assess shifts in the evaluation of lobotomy.
      Textbooks of medical decision making generally recommend that decisions under
      risk are made so as to maximise expected utility (MEU) I show that using this
      procedure suggests that the 1940s and 1950s practice of psychosurgery was
      justifiable. In making sense of this finding we have a choice: Either we can
      accept that psychosurgery was justified, in which case condemnation of the
      lobotomists is misplaced. Or, we can conclude that the use of formal decision
      procedures, such as MEU, is problematic. 

PMID- 24449252
TI  - Enhanced electroactive response of unidirectional elastomeric composites with
      high-dielectric-constant fibers.
AB  - A fiber-elastomer composite design with a vastly improved and directional
      actuation response is proposed for dielectric elastomer actuators. The all
      elastomer composites are capable of achieving remarkably high actuation stresses,
      directional strains, electromechanical coupling efficiencies, and energy
      densities at relatively low electric fields. Their electromechanical metrics are
      among the highest reported for this class of electroactive materials. 

PMID- 24449253
TI  - Using an organic molecule with low triplet energy as a host in a highly efficient
      blue electrophosphorescent device.
AB  - To achieve high efficiencies in blue phosphorescent organic light-emitting diodes
      (PhOLEDs), the triplet energies (T1) of host materials are generally supposed to
      be higher than the blue phosphors. A small organic molecule with low singlet
      energy (S1) of 2.80 eV and triplet energy of 2.71 eV can be used as the host
      material for the blue phosphor, [bis(4,6-difluorophenylpyridinato
      N,C(2'))iridium(III)] tetrakis(1-pyrazolyl)borate (FIr6; T1=2.73 eV). In both the
      photo- and electro-excited processes, the energy transfer from the host material
      to FIr6 was found to be efficient. In a three organic-layer device, the maximum
      current efficiency of 37 cd A(-1) and power efficiency of 40 Lm W(-1) were
      achieved for the FIr6-based blue PhOLEDs.

PMID- 24449254
TI  - Comparison of carotid artery dimensions and lesion length measured by B-mode
      ultrasonography and quantitative angiography in patients with severe stenosis
      undergoing percutaneous revascularization.
AB  - BACKGROUND: To evaluate the correlation and agreement of the carotid artery
      landmarks necessary for carotid artery stenting obtained by B-mode
      ultrasonography (BMU), and by quantitative angiography (QCA) in patients with
      severe carotid artery stenosis. METHODS: In 75 patients undergoing carotid artery
      stenting, the distal common (CCA), proximal internal (ICA) carotid artery
      diameter, and lesion length were measured preoperatively by BMU, and
      intraoperatively by QCA. RESULTS: In 96% of the subjects, BMU imaging was
      adequate for interpretation. BMU and QCA Pearson correlation and Lin concordance
      coefficients were 0.75 (p < 0.001) and 0.959 (95% CI: 0.930 - 0.996),
      respectively, for CCA diameter, 0.88 (p < 0.001) and 0.954 (95% CI: 0.928-0.983),
      respectively, for ICA diameter, and 0.62 (p < 0.001) and 0.734 (95% CI: 0.719
      0.760), respectively, for lesion length, with a 0.765 bias correction factor and
      a wider data scatter by Bland Altman plots showing shorter lesion length by BMU
      than by QCA. CONCLUSIONS: In patients with carotid artery stenosis, BMU can
      provide reliable distal CCA and proximal ICA diameters in comparison with QCA,
      whereas lesion length measured by BMU has an acceptable correlation, but a poor
      agreement with QCA.

PMID- 24449255
TI  - Persistent Wnt/beta-catenin signaling determines dorsalization of the postnatal
      subventricular zone and neural stem cell specification into oligodendrocytes and
      glutamatergic neurons.
AB  - In the postnatal and adult central nervous system (CNS), the subventricular zone
      (SVZ) of the forebrain is the main source of neural stem cells (NSCs) that
      generate olfactory neurons and oligodendrocytes (OLs), the myelinating cells of
      the CNS. Here, we provide evidence of a primary role for canonical Wnt/beta
      catenin signaling in regulating NSC fate along neuronal and oligodendroglial
      lineages in the postnatal SVZ. Our findings demonstrate that glutamatergic
      neuronal precursors (NPs) and oligodendrocyte precursors (OPs) are derived
      strictly from the dorsal SVZ (dSVZ) microdomain under the control of Wnt/beta
      catenin, whereas GABAergic NPs are derived mainly from the lateral SVZ (lSVZ)
      microdomain independent of Wnt/beta-catenin. Transcript analysis of
      microdissected SVZ microdomains revealed that canonical Wnt/beta-catenin
      signaling was more pronounced in the dSVZ microdomain. This was confirmed using
      the beta-catenin-activated Wnt-reporter mouse and by pharmacological stimulation
      of Wnt/beta-catenin by infusion of the specific glycogen synthase kinase 3beta
      inhibitor, AR-A014418, which profoundly increased the generation of cycling
      cells. In vivo genetic/pharmacological stimulation or inhibition of Wnt/beta
      catenin, respectively, increased and decreased the differentiation of dSVZ-NSCs
      into glutamatergic NPs, and had a converse effect on GABAergic NPs. Activation of
      Wnt/beta-catenin dramatically stimulated the generation of OPs, but its
      inhibition had no effect, indicating other factors act in concert with Wnt/beta
      catenin to fine tune oligodendrogliogenesis in the postnatal dSVZ. These results
      demonstrate a role for Wnt/beta-catenin signaling within the dorsal microdomain
      of the postnatal SVZ, in regulating the genesis of glutamatergic neurons and OLs.

PMID- 24449256
TI  - Management of recurrent thrombosis in antiphospholipid syndrome.
AB  - One of the challenges of managing patients with antiphospholipid syndrome is the
      prevention of rethrombosis (secondary prophylaxis). Risk stratification, i.e.
      traditional cardiovascular and thrombosis risk factors, systemic autoimmune
      diseases, antiphospholipid antibody profile, and the intensity of anticoagulation
      are all relevant to the management of APS patients with recurrent thrombosis. The
      paper will review "state of the art" strategies for optimizing therapy for APS
      patients with recurrent thrombosis. 

PMID- 24449258
TI  - New anticoagulants should be considered for atrial fibrillation, says NICE.

PMID- 24449259
TI  - Oral health of the Paleoamericans of Lagoa Santa, Central Brazil.
AB  - The peopling, origins, and early prehistory of the Americas are topics of intense
      debate. However, few studies have used human remains to document and interpret
      patterns of health and lifestyle of Paleoamericans. This study provides the first
      investigation to characterize oral health in a series of early Holocene skeletal
      remains from Lagoa Santa, Brazil, a locality containing the remains of some of
      the earliest inhabitants of South America (10,000-7,000 BP). The sample is
      composed of 949 teeth and 1925 alveoli from an estimated 113 individuals
      excavated from 17 archaeological sites located in the State of Minas Gerais. We
      compare dental caries and abscess prevalence at Lagoa Santa to a large sample of
      human skeletons from the Western Hemisphere Project (WHP) database using both
      individual and tooth/alveolus count methods. In addition, antemortem tooth loss
      and tooth wear were analyzed in Lagoa Santa by sex and age. The results show that
      Lagoa Santa dental caries and abscess prevalence are significantly higher than
      observed among other hunter-gatherers included in the WHP database, except when
      abscess prevalence is considered by individual count. Adult females have less
      tooth wear coupled with higher prevalence of dental caries and antemortem tooth
      loss than adult males. These results point to an unexpected record of poor oral
      health at Lagoa Santa, especially among females. A diet based on a highly
      cariogenic combination of wild tubers and fruits is suggested as an explanation
      for the elevated rate, characterizing an early adaptation to a tropical
      environment in South America.

PMID- 24449257
TI  - Impact of sequence on the molecular assembly of short amyloid peptides.
AB  - The goal of this work is to understand how the sequence of a protein affects the
      likelihood that it will form an amyloid fibril and the kinetics along the
      fibrillization pathway. The focus is on very short fragments of amyloid proteins
      since these play a role in the fibrillization of the parent protein and can form
      fibrils themselves. Discontinuous molecular dynamics simulations using the
      PRIME20 force field were performed of the aggregation of 48-peptide systems
      containing SNQNNF (PrP (170-175)), SSTSAA (RNaseA(15-20)), MVGGVV (Abeta(35-40)),
      GGVVIA (Abeta(37-42)), and MVGGVVIA (Abeta(35-42)). In our simulations SNQQNF,
      SSTTSAA, and MVGGVV form large numbers of fibrillar structures spontaneously (as
      in experiment). GGVVIA forms beta-sheets that do not stack into fibrils (unlike
      experiment). The combination sequence MVGGVVIA forms less fibrils than MVGGVV,
      hindered by the presence of the hydrophobic residues at the C-terminal. Analysis
      of the simulation kinetics and energetics reveals why MVGGVV forms fibrils and
      GGVVIA does not, and why adding I and A to MVGGVVIA reduces fibrillization and
      enhances amorphous aggregation into oligomeric structures. The latter helps
      explain why Abeta(1-42) assembles into more complex oligomers than Abeta(1-40), a
      consequence of which is that it is more strongly associated with Alzheimer's
      disease.

PMID- 24449260
TI  - The role of the ventral dentate gyrus in olfactory pattern separation.
AB  - Dorsoventral lesion studies of the hippocampus have indicated that the dorsal
      axis of the hippocampus is important for spatial processing and the ventral axis
      of the hippocampus is important for olfactory learning and memory and anxiety.
      There is some evidence to suggest that the ventral CA3 and ventral CA1 conduct
      parallel processes for pattern completion and temporal processing, respectively.
      Studies have indicated that the dorsal dentate gyrus (DG) is importantly involved
      in processes reflecting underlying pattern separation activity for spatial
      information. However, the ventral DG is less understood. The current study
      investigated the less-understood role of the ventral DG in olfactory pattern
      separation. A series of odor stimuli that varied on only one level, number of
      carbon chains (methyl groups), was used in a matching-to-sample paradigm in order
      to investigate ventral DG involvement in working memory for similar and less
      similar odors. Rats with ventral DG lesions were impaired at delays of 60 sec,
      but not at delays of 15 sec. A memory-based pattern separation effect was
      observed performance was poorest with only one carbon chain separation between
      trial odors and was highest for trials with four separations. The present study
      indicates that the ventral DG plays an important role in olfactory learning and
      memory processes for highly similar odors. The results also indicate a role for
      the ventral DG in pattern separation for odor information, which may have further
      implications for parallel processing across the dorsoventral axis for the DG in
      spatial (dorsal) and olfactory (ventral) pattern separation.

PMID- 24449261
TI  - Simple technique for gasless transumbilical single-incisional laparoscopic
      assisted appendectomy.
AB  - PURPOSE: Single-incision laparoscopic surgery has recently received more
      attention. We developed a novel simple technique of gasless transumbilical single
      incisional laparoscopic-assisted appendectomy (TUSILAA) and retrospectively
      analyzed our initial experience. METHODS: TUSILAA has been attempted in 50
      consecutive patients with acute appendicitis. The vertical incision through the
      umbilicus was used for laparoscopic access and the abdominal wall was lifted by a
      Kent retractor set system. RESULTS: Our technique was successful in 45 out of 50
      (90 %) patients. The median operating time was 59 min (range 35-140). The median
      length of postoperative hospital stay was 4 days (range 2-12). None of the cases
      were converted to open appendectomy. There were no perioperative surgical
      complications. CONCLUSIONS: Our novel technique, gasless TUSILAA, is safe and
      feasible with acceptable operative time and excellent cosmetic result.
      Furthermore, this procedure has the advantage of cost-effectiveness since any
      disposable instruments including trocars, staplers, or expensive devices are not
      required. Therefore, this could be used as the first-choice surgical procedure
      for selected patients with uncomplicated acute appendicitis.

PMID- 24449262
TI  - Obesity, Physical Activity, and Sedentary Behavior of Youth With Learning
      Disabilities and ADHD.
AB  - Obesity, physical activity, and sedentary behavior in childhood are important
      indicators of present and future health and are associated with school-related
      outcomes such as academic achievement, behavior, peer relationships, and self
      esteem. Using logistic regression models that controlled for gender, age,
      ethnicity/race, and socioeconomic status, we investigated the likelihood that
      youth with learning disabilities (LD) and attention-deficit/hyperactivity
      disorder (ADHD) are obese, physically active, and sedentary using a nationally
      representative sample of 45,897 youth in the United States from 10 to 17 years of
      age. Results indicated that youth with comorbid LD/ADHD were significantly more
      likely than peers without LD or ADHD to be obese; that youth with LD only, ADHD
      only, and comorbid LD/ADHD were significantly less likely to meet recommended
      levels of physical activity; and that youth with LD only were significantly more
      likely to exceed recommended levels of sedentary behavior. Medication status
      mediated outcomes for youth with ADHD. We offer school-based recommendations for
      improving health-related outcomes for students with LD and ADHD. 

PMID- 24449265
TI  - Fabrication of a light-emitting shape memory polymeric web containing indocyanine
      green.
AB  - Dye-containing polymers are highly desired for a number of commercially and
      medically relevant applications, such as sensors, medical devices, and drug
      delivery. In particular, dyes that emit light in the NIR region of the
      electromagnetic spectrum are of great interest due to the window of transparency
      for mammalian soft tissue in this range. While the incorporation of dyes into
      polymeric hosts by diffusion is a method that has been widely used, this approach
      is problematic in that it lacks uniformity and control over the incorporation.
      Here, we sought to develop NIR-emitting polymeric materials with high
      fluorescence intensity, addressing the problem of uniformity by incorporating the
      dye in a polymer host using dissolution in a mutual solvent and subsequent
      electrospinning into a fibrous web. This web could be prepared as a free-standing
      film, a coating or, as we will show, a shrink-wrap medical device label. The
      primary findings of this study were that an optimal concentration of dye in the
      polymer host exists, that the fluorescence intensity for fibrous webs greatly
      exceed that of comparable cast films, and that the dye-containing webs feature
      water-triggered contraction of use for application to medical devices, such as
      feeding tubes or catheters.

PMID- 24449263
TI  - Adiponectin, resistin and leptin in paediatric chronic renal failure: correlation
      with auxological and endocrine profiles.
AB  - INTRODUCTION: Chronic renal failure (CRF) compromises nutrition, growth, puberty,
      glycometabolic homeostasis, and adipokine secretion (i.e. adiponectin, resistin,
      and leptin). Adipokines play a role in the clinical outcome, but data in
      paediatric patients is scant. AIM: To evaluate the link between kidney function,
      adiponectin, resistin, leptin, hormonal status, nutritional state and late
      outcome of CRF children. MATERIALS AND METHODS: We studied leptin, adiponectin
      and resistin levels in 31 CRF patients (19 males, 12 females, aged 12.1 +/- 4.47
      years) managed conservatively, and 30 healthy age- and gender-matched controls.
      Clinical, auxological, biochemical, hormonal data, glucose and insulin levels
      were correlated with adipokine levels. RESULTS: Six percent of patients had
      glycaemia T0' > 126 mg/dl, 23 % glycaemia T60' > 126, and 23 % glycaemia T120' >=
      140. Glycated haemoglobin (HbA1c) measured during follow-up was in the normal
      range in all patients (4-5.6 %). Insulinaemia was significantly higher in CRF
      patients than controls. Homeostatic model of assessment-insulin resistance (HOMA
      IR) levels were more elevated in patients (32 % had HOMA-IR > 2.5) than controls.
      Leptin levels were significantly higher in CRF patients than controls and
      differed significantly between males and females. Leptin correlated significantly
      with creatinine, body mass index (BMI), BA, pubertal stage, insulin-like growth
      factor 1, and HOMA-IR in females. Adiponectin levels were significantly higher in
      patients than controls, higher in patients with BMI < 85th centile and
      significantly inversely correlated to BMI, BA, haemoglobin, ferritin, proteins,
      albumin, and creatininuria. Resistin levels showed a direct correlation with C
      reactive protein and an inverse correlation with haemoglobin. CONCLUSION: Normal
      resistin levels are an expression of both adequate nutritional state and
      controlled inflammatory state. Adiponectin could protect against chronic
      inflammation, atherosclerosis, and cardiovascular diseases. Preventing obesity
      and ensuring a correct nutritional state are primary goals for physicians
      following children with CRF. Adipokines could be a useful marker in the follow
      up.

PMID- 24449266
TI  - Successful treatment of severe carbamazepine toxicity with 5% albumin-enhanced
      continuous venovenous hemodialysis.
AB  - Carbamazepine overdose is a common, toxic ingestion, manifesting as central
      nervous system (CNS) and respiratory depression. Carbamazepine is highly protein
      bound with a large volume of distribution and, therefore, inefficiently removed
      by conventional hemodialysis. We describe the successful use of continuous
      venovenous hemodialysis (CVVHD) with 5% albumin enhanced dialysate in a 31-year
      old female who developed CNS depression, hypotension and respiratory failure,
      requiring mechanical ventilation, after an intentional ingestion of approximately
      10 g of extended release carbamazepine, Tegretol CR((r)). The peak drug level was
      26 mcg/ml, therapeutic range 8-12 mcg/ml, with toxicity often developing a level
      above 15 mcg/ml. Normal half-life of drug elimination is 35-60 h in carbamazepine
      naive patients. In contrast, with albumin-enhanced dialysis, we observed a drug
      half-life of 18 h. She was extubated on day two and was transferred to inpatient
      psychiatry by day 3 without significant neurologic sequelae. In vitro studies
      have been done with bovine blood demonstrating significant carbamazepine removal
      using CVVHD with albumin-enhanced dialysate. There has been very limited
      experience using albumin-enhanced CVVHD in an adult patient with carbamazepine
      toxicity.

PMID- 24449268
TI  - Spatial control of phospholipid flux restricts endoplasmic reticulum sheet
      formation to allow nuclear envelope breakdown.
AB  - The nuclear envelope is a subdomain of the endoplasmic reticulum (ER). Here we
      characterize CNEP-1 (CTD [C-terminal domain] nuclear envelope phosphatase-1), a
      nuclear envelope-enriched activator of the ER-associated phosphatidic acid
      phosphatase lipin that promotes synthesis of major membrane phospholipids over
      phosphatidylinositol (PI). CNEP-1 inhibition led to ectopic ER sheets in the
      vicinity of the nucleus that encased the nuclear envelope and interfered with
      nuclear envelope breakdown (NEBD) during cell division. Reducing PI synthesis
      suppressed these phenotypes, indicating that CNEP-1 spatially regulates
      phospholipid flux, biasing it away from PI production in the vicinity of the
      nuclear envelope to prevent excess ER sheet formation and NEBD defects. 

PMID- 24449267
TI  - Cellular senescence and its effector programs.
AB  - Cellular senescence is a stress response that accompanies stable exit from the
      cell cycle. Classically, senescence, particularly in human cells, involves the
      p53 and p16/Rb pathways, and often both of these tumor suppressor pathways need
      to be abrogated to bypass senescence. In parallel, a number of effector
      mechanisms of senescence have been identified and characterized. These studies
      suggest that senescence is a collective phenotype of these multiple effectors,
      and their intensity and combination can be different depending on triggers and
      cell types, conferring a complex and diverse nature to senescence. Series of
      studies on senescence-associated secretory phenotype (SASP) in particular have
      revealed various layers of functionality of senescent cells in vivo. Here we
      discuss some key features of senescence effectors and attempt to functionally
      link them when it is possible. 

PMID- 24449269
TI  - Mechanical motion promotes expression of Prg4 in articular cartilage via multiple
      CREB-dependent, fluid flow shear stress-induced signaling pathways.
AB  - Lubricin is a secreted proteoglycan encoded by the Prg4 locus that is abundantly
      expressed by superficial zone articular chondrocytes and has been noted to both
      be sensitive to mechanical loading and protect against the development of
      osteoarthritis. In this study, we document that running induces maximal
      expression of Prg4 in the superficial zone of knee joint articular cartilage in a
      COX-2-dependent fashion, which correlates with augmented levels of phospho-S133
      CREB and increased nuclear localization of CREB-regulated transcriptional
      coactivators (CRTCs) in this tissue. Furthermore, we found that fluid flow shear
      stress (FFSS) increases secretion of extracellular PGE2, PTHrP, and ATP (by
      epiphyseal chondrocytes), which together engage both PKA- and Ca(++)-regulated
      signaling pathways that work in combination to promote CREB-dependent induction
      of Prg4, specifically in superficial zone articular chondrocytes. Because running
      and FFSS both boost Prg4 expression in a COX-2-dependent fashion, our results
      suggest that mechanical motion may induce Prg4 expression in the superficial zone
      of articular cartilage by engaging the same signaling pathways activated in vitro
      by FFSS that promote CREB-dependent gene expression in this tissue. 

PMID- 24449270
TI  - A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere
      shortening in mice.
AB  - The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often
      caused by mutations in telomerase or the factors involved in telomerase
      biogenesis and trafficking. However, a subset of DC patients is heterozygous for
      mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations
      affect telomere function, we generated mice with the equivalent of the TIN2 K280E
      DC allele (TIN2(DC)) by gene targeting. Whereas homozygous TIN2(DC/DC) mice were
      not viable, first-generation TIN2(+/DC) mice were healthy and fertile. In the
      second and third generations, the TIN2(+/DC) mice developed mild pancytopenia,
      consistent with hematopoietic dysfunction in DC, as well as diminished fecundity.
      Bone marrow telomeres of TIN2(+/DC) mice shortened over the generations, and
      immortalized TIN2(+/DC) mouse embryonic fibroblasts (MEFs) showed telomere
      shortening with proliferation. Unexpectedly, telomere shortening was accelerated
      in TIN2(+/DC) mTR(-/-) mice and MEFs compared with TIN2(+/+) mTR(-/-) controls,
      establishing that the TIN2(DC) telomere maintenance defect was not solely due to
      diminished telomerase action. The TIN2(DC) allele induced mild ATR kinase
      signaling at telomeres and a fragile telomere phenotype, suggestive of telomere
      replication problems. These data suggest that this TIN2-DC mutation could induce
      telomeric dysfunction phenotypes in telomerase-negative somatic cells and tissues
      that further exacerbate the telomere maintenance problems in telomerase-positive
      stem cell compartments. 

PMID- 24449272
TI  - A hierarchical model for assembly of eukaryotic 60S ribosomal subunit domains.
AB  - Despite having high-resolution structures for eukaryotic large ribosomal
      subunits, it remained unclear how these ribonucleoprotein complexes are
      constructed in living cells. Nevertheless, knowing where ribosomal proteins
      interact with ribosomal RNA (rRNA) provides a strategic platform to investigate
      the connection between spatial and temporal aspects of 60S subunit biogenesis. We
      previously found that the function of individual yeast large subunit ribosomal
      proteins (RPLs) in precursor rRNA (pre-rRNA) processing correlates with their
      location in the structure of mature 60S subunits. This observation suggested that
      there is an order by which 60S subunits are formed. To test this model, we used
      proteomic approaches to assay changes in the levels of ribosomal proteins and
      assembly factors in preribosomes when RPLs functioning in early, middle, and late
      steps of pre-60S assembly are depleted. Our results demonstrate that structural
      domains of eukaryotic 60S ribosomal subunits are formed in a hierarchical
      fashion. Assembly begins at the convex solvent side, followed by the polypeptide
      exit tunnel, the intersubunit side, and finally the central protuberance. This
      model provides an initial paradigm for the sequential assembly of eukaryotic 60S
      subunits. Our results reveal striking differences and similarities between
      assembly of bacterial and eukaryotic large ribosomal subunits, providing insights
      into how these RNA-protein particles evolved. 

PMID- 24449273
TI  - Extrinsic pulmonary stenosis in primary mediastinal B-cellular lymphoma.
AB  - We describe the case of a 34-year-old man with a history of asthenia and
      excessive fatigability. Transthoracic echocardiography showed a mass in the right
      ventricular outflow tract with a peak systolic gradient of 52 mmHg. Contrast
      enhanced CT confirmed the presence of a lobulated mass, which extensively filled
      the anterior mediastinum, infiltrating the pulmonary artery trunk up to occupying
      the right ventricular outflow tract. CT-guided biopsy revealed primary
      mediastinal B-cellular lymphoma. The patient underwent chemotherapy, achieving
      complete remission of the disease at the 12-month follow-up, while the gradient
      across the pulmonary artery dropped from 52 mmHg to 14 mmHg.

PMID- 24449271
TI  - Zrf1 is required to establish and maintain neural progenitor identity.
AB  - The molecular mechanisms underlying specification from embryonic stem cells
      (ESCs) and maintenance of neural progenitor cells (NPCs) are largely unknown.
      Recently, we reported that the Zuotin-related factor 1 (Zrf1) is necessary for
      chromatin displacement of the Polycomb-repressive complex 1 (PRC1). We found that
      Zrf1 is required for NPC specification from ESCs and that it promotes the
      expression of NPC markers, including the key regulator Pax6. Moreover, Zrf1 is
      essential to establish and maintain Wnt ligand expression levels, which are
      necessary for NPC self-renewal. Reactivation of proper Wnt signaling in Zrf1
      depleted NPCs restores Pax6 expression and the self-renewal capacity. ESC-derived
      NPCs in vitro resemble most of the characteristics of the self-renewing NPCs
      located in the developing embryonic cortex, which are termed radial glial cells
      (RGCs). Depletion of Zrf1 in vivo impairs the expression of key self-renewal
      regulators and Wnt ligand genes in RGCs. Thus, we demonstrate that Zrf1 plays an
      essential role in NPC generation and maintenance. 

PMID- 24449274
TI  - HLA variation reveals genetic continuity rather than population group structure
      in East Asia.
AB  - Genetic differences between Northeast Asian (NEA) and Southeast Asian (SEA)
      populations have been observed in numerous studies. At the among-population
      level, despite a clear north-south differentiation observed for many genetic
      markers, debates were led between abrupt differences and a continuous pattern. At
      the within-population level, whether NEA or SEA populations have higher genetic
      diversity is also highly controversial. In this study, we analyzed a large set of
      HLA data from East Asia in order to map the genetic variation among and within
      populations in this continent and to clarify the distribution pattern of HLA
      lineages and alleles. We observed a genetic differentiation between NEA and SEA
      populations following a continuous pattern from north to south, and we show a
      significant and continuous decrease of HLA diversity by the same direction. This
      continuity is shaped by clinal distributions of many HLA lineages and alleles
      with increasing or decreasing frequencies along the latitude. These results bring
      new evidence in favor of the "overlapping model" proposed previously for East
      Asian peopling history, whereby modern humans migrated eastward from western
      Eurasia via two independent routes along each side of the Himalayas and, later,
      overlapped in East Asia across open land areas. Our study strongly suggests that
      intensive gene flow between NEA and SEA populations occurred and shaped the
      latitude-related continuous pattern of genetic variation and the peculiar HLA
      lineage and allele distributions observed in this continent. Probably for a very
      long period, the exact duration of these events remains to be estimated. 

PMID- 24449275
TI  - Thread insertion of a bis(dipyridophenazine) diruthenium complex into the DNA
      double helix by the extrusion of AT base pairs and cross-linking of DNA duplexes.
AB  - The crystal structure of the Delta,Delta enantiomer of the binuclear "light
      switch" ruthenium complex [MU-(11,11'-bidppz)(1,10-phenanthroline)4  Ru2 ](4+)
      bound to the oligonucleotide d(CGTACG) shows that one dppz moiety of the dumbbell
      like compound inserts into the DNA stack through the extrusion of an AT base
      pair. The second dppz moiety recruits a neighboring DNA molecule, and the complex
      thus cross-links two adjacent duplexes by bridging their major grooves. 

PMID- 24449276
TI  - Models of calcium permeation through T-type channels.
AB  - Ca(2+) entry is indispensable part of intracellular Ca(2+) signaling, which is
      vital for most of cellular functions. Low voltage-activated (LVA or T-type)
      calcium channels belong to the family of voltage-gated calcium channels (VGCCs)
      which provide Ca(2+) entry in response to membrane depolarization. VGCCs are
      generally characterized by exceptional Ca(2+) selectivity combined with high
      permeation rate, thought to be determined by the presence in their selectivity
      filter of a versatile Ca(2+) binding site formed by four glutamate residues (EEEE
      motif). The subfamily of LVA channels includes three members, Cav3.1, Cav3.2 and
      Cav3.3. They all possess two aspartates instead of glutamates (i.e., EEDD motif)
      in their selectivity filter and are the least Ca(2+)-selective of all VGCCs. They
      also have the lowest conductance, weakly discriminate Ca(2+), Sr(2+) and Ba(2+)
      and demonstrate channel-specific sensitivity to divalent metal blockers, such as
      Ni(2+). The available data suggest that EEDD binding site of LVA channels is more
      rigid compared to EEEE one, and their selectivity permeation and block are
      determined by two supplementary low-affinity intrapore Ca(2+) binding sites
      located above and below EEDD locus. In addition, LVA channels have extracellular
      metal binding site that allosterically regulates channel's gating, permeation and
      block depending on trace metals concentration. 

PMID- 24449279
TI  - [Radiology workplace 2.0].

PMID- 24449277
TI  - T-type calcium channels blockers as new tools in cancer therapies.
AB  - T-type calcium channels are involved in a multitude of cellular processes, both
      physiological and pathological, including cancer. T-type channels are also often
      aberrantly expressed in different human cancers and participate in the regulation
      of cell cycle progression, proliferation, migration, and survival. Here, we
      review the recent literature and discuss the controversies, supporting the role
      of T-type Ca(2+) channels in cancer cells and the proposed use of channels
      blockers as anticancer agents. A growing number of reports show that
      pharmacological inhibition or RNAi-mediated downregulation of T-type channels
      leads to inhibition of cancer cell proliferation and increased cancer cell death.
      In addition to a single agent activity, experimental results demonstrate that T
      type channel blockers enhance the anticancer effects of conventional radio- and
      chemotherapy. At present, the detailed biological mechanism(s) underlying the
      anticancer activity of these channel blockers is not fully understood. Recent
      findings and ideas summarized here identify T-type Ca(2+) channels as a molecular
      target for anticancer therapy and offer new directions for the design of novel
      therapeutic strategies employing channels blockers. Physiological relevance: T
      type calcium channels are often aberrantly expressed or deregulated in cancer
      cells, supporting their proliferation, survival, and resistance to treatment;
      therefore, T-type Ca(2+) channels could be attractive molecular targets for
      anticancer therapy. 

PMID- 24449280
TI  - [Radiology in combination with hospital communication - challenges, solutions and
      pitfalls : radiology IT as important component of electronic patient records in
      the University Hospital Hamburg-Eppendorf (UKE)].
AB  - BACKGROUND: Radiological information technology (IT) is nowadays one of many
      components of an integrated hospital IT structure. OBJECTIVE: This review article
      is concerned with the challenges of a comprehensive and complete integration of
      all documented information and communication of all medical disciplines in a
      hospital in the electronic patient records. Special attention is paid to the role
      of radiology and the interface between radiological and clinical systems.
      PERSPECTIVES: The utilization of the documented data paying special attention to
      the requirements of data protection is a core aim for the further development of
      electronic patient records in the University Hospital Hamburg-Eppendorf in the
      coming years.

PMID- 24449278
TI  - SIRT1 positively regulates autophagy and mitochondria function in embryonic stem
      cells under oxidative stress.
AB  - SIRT1, an NAD-dependent deacetylase, plays a role in regulation of autophagy.
      SIRT1 increases mitochondrial function and reduces oxidative stress, and has been
      linked to age-related reactive oxygen species (ROS) generation, which is highly
      dependent on mitochondrial metabolism. H2O2 induces oxidative stress and
      autophagic cell death through interference with Beclin 1 and the mTOR signaling
      pathways. We evaluated connections between SIRT1 activity and induction of
      autophagy in murine (m) and human (h) embryonic stem cells (ESCs) upon ROS
      challenge. Exogenous H2 O2 (1 mM) induced apoptosis and autophagy in wild-type
      (WT) and Sirt1-/- mESCs. High concentrations of H2O2 (1 mM) induced more
      apoptosis in Sirt1-/-, than in WT mESCs. However, addition of 3-methyladenine, a
      widely used autophagy inhibitor, in combination with H2O2 induced more cell death
      in WT than in Sirt1-/- mESCs. Decreased induction of autophagy in Sirt1-/- mESCs
      was demonstrated by decreased conversion of LC3-I to LC3-II, lowered expression
      of Beclin-1, and decreased LC3 punctae and LysoTracker staining. H2O2 induced
      autophagy with loss of mitochondrial membrane potential and disruption of
      mitochondrial dynamics in Sirt1-/- mESCs. Increased phosphorylation of P70/85-S6
      kinase and ribosomal S6 was noted in Sirt1-/- mESCs, suggesting that SIRT1
      regulates the mTOR pathway. Consistent with effects in mESCs, inhibition of SIRT1
      using Lentivirus-mediated SIRT1 shRNA in hESCs demonstrated that knockdown of
      SIRT1 decreased H2O2-induced autophagy. This suggests a role for SIRT1 in
      regulating autophagy and mitochondria function in ESCs upon oxidative stress,
      effects mediated at least in part by the class III PI3K/Beclin 1 and mTOR
      pathways.

PMID- 24449281
TI  - [Improvement of the processes around the radiology workplace : avoidance of time
      delays].
AB  - Radiologists have been confronted with multiple new challenges in recent years.
      While there has been a steady increase in the number of radiological examinations
      and imaging material per examination, examination protocols have become more
      complex and highly time-consuming whereas case-based remuneration is on the
      decline. The identification of inefficient components in examination processes
      and reporting is therefore essential. Where and why do time delays occur? How can
      they be avoided? The following article provides a brief overview and is designed
      to stimulate discussion. 

PMID- 24449282
TI  - [Radiological media and modern supporting tools in radiology].
AB  - Radiology is a field with a high demand on information. Nowadays, a huge variety
      of electronic media and tools exists in addition to the classical media.
      Asynchronous and synchronous e-learning are constantly growing and support
      radiology with case collections, webinars and online textbooks. Various internet
      resources, social media and online courses have been established. Dynamic
      websites show a variety of interactive elements and it is easier and faster to
      access large amounts of data. Social media have an exponentially growing number
      of users and enable an efficient collaboration as well as forming professional
      networks. Massive open online courses (MOOCs) complete the offer of education and
      increase the opportunity to take part in educational activities. Apart from the
      existing variety of resources it is essential to focus on a critical selection
      for using these radiological media. It is reasonable to combine classical and
      electronic media instead of a one-sided use. As dynamic as the progress in the
      field of radiological media and its tools may be, the personal contact remains
      and should be maintained. 

PMID- 24449285
TI  - Incremental burden of disease in patients diagnosed with pulmonary arterial
      hypertension receiving monotherapy and combination vasodilator therapy.
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare, severely
      debilitating disease with high mortality. There are limited data available on
      treatment patterns and burden of disease from conditions of actual care. METHODS:
      This analysis assesses the burden of disease for patients with PAH treated with
      monotherapy and combination therapies excluding and including intravenous (IV)
      prostacyclin analogues (PGI2). Data were drawn from the Adelphi PAH Disease
      Specific Programme, a cross sectional survey of consulting patients undertaken in
      the US, Germany, Italy and the UK in 2010. Outcomes included demographics,
      clinical characteristics, health-care resource utilization, and quality of life
      measured by the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).
      RESULTS: Data were analyzed from 446 patients receiving >=1 of 3 PAH-specific
      treatment classes. Physicians comprised mainly pulmonologists and cardiologists.
      The symptoms, functioning and quality of life scales of the CAMPHOR instrument
      were completed by 218, 229, and 214 patients, respectively. Although 46.2% of
      patients were classified as World Health Organization (WHO) functional class III
      or IV, only 24.4% of the population received combination therapy. Combination
      therapy including IV PGI2 was used in 4.7% of all patients. Patients on
      monotherapy had the lowest pulmonary vascular resistance values, the highest
      recorded 6-min walk distance and the lowest recorded levels of dyspnea. Patients
      on combination therapy including IV PGI2 scored worse on all three variables and
      had more hospitalizations than patients on less aggressive combination therapy.
      With increasing therapeutic regimens, the CAMPHOR scores were higher, indicating
      worse states of health. CONCLUSIONS: Combination treatment and particularly the
      use of prostacyclins remain underused in an unselected population of PAH patients
      surveyed under conditions of actual care. The disease burden is substantial and
      increases with greater severity of disease and more aggressive treatments. This
      necessitates improvement in optimizing current therapy, as well as novel and
      innovative combination options.

PMID- 24449284
TI  - Polyarticular septic arthritis in an 11-year-old child.
AB  - A child with polyarthritis is always a diagnostic challenge for the treating
      physician. Polyarthritis can be a clinical manifestation of diverse disease
      processes, and the differential diagnosis is understandably very broad. We
      present a case of polyarticular septic arthritis, which is osteomyelitis
      complicated, caused by Streptococcus pyogenes identified by 16S polymerase chain
      reaction (PCR) in a healthy child, with previous synovial fluid cultures
      negative. This case underlines the importance of early aggressive therapy and the
      role of PCR/16S ribosomal bacterial DNA amplification to detect the causative
      microorganisms in septic arthritis when cultures remain negative. 

PMID- 24449286
TI  - The perceptual richness of complex memory episodes is compromised by medial
      temporal lobe damage.
AB  - Perceptual richness, a defining feature of episodic memory, emerges from the
      reliving of multimodal sensory experiences. Although the importance of the medial
      temporal lobe (MTL) to episodic memory retrieval is well documented, the features
      that determine its engagement are not well characterized. The current study
      assessed the relationship between MTL function and episodic memory's perceptual
      richness. We designed a laboratory memory task meant to capture the complexity of
      memory for life episodes, while manipulating memory's perceptual content.
      Participants encoded laboratory episodes with rich (film clips) and impoverished
      (written narratives) perceptual content that were matched for other
      characteristics such as personal significance, emotionality and story content. At
      retrieval, participants were probed to describe the stories' perceptual features
      and storyline. Participants also recalled autobiographical memories (AMs) in a
      comparison condition. We compared the performance of patients with unilateral
      medial temporal lobe epilepsy (mTLE) and healthy controls to assess how damage to
      the MTL affects retrieval in these conditions. We observed an overall decrease in
      detail count in the mTLE group, along with a disproportionate deficit in
      perceptual details that was most acute in the AM and the perceptually enriched
      film clip conditions. Our results suggest that the impaired sense of reliving the
      past that accompanies MTL insult is mediated by a paucity of perceptual episodic
      memory details. We also introduce a new protocol that successfully mimics
      naturalistic memories while benefiting from the experimental control provided by
      using laboratory stimuli.

PMID- 24449288
TI  - Multiple dimensions of embodiment in medical practices.
AB  - In this paper I explore the various meanings of embodiment from a patient's
      perspective. Resorting to phenomenology of health and medicine, I take the idea
      of 'lived experience' as starting point. On the basis of an analysis of
      phenomenology's call for bracketing the natural attitude and its reduction to the
      transcendental, I will explain, however, that in medical phenomenological
      literature 'lived experience' is commonly one-sidedly interpreted. In my paper, I
      clarify in what way the idea of 'lived experience' should be revisited and,
      subsequently, what this reconsideration means for phenomenological research on
      embodiment in health and medicine. The insight that the body is a condition of
      possibility for world-disclosing yet, at the same time, itself conditioned by
      this world forces us to not only zoom in on the body's subject-side, but also on
      its object-side. I argue that in order to render account for this double body
      ontology, phenomenology should include empirical sociological analyses as well. I
      thus argue in favor of the idea of a socio-phenomenology. Drawing on material
      from my own research project on embodied self-experiences after breast surgery, I
      show how this approach can be fruitful in interpreting the impact of
      disfigurements on a person's embodied agency, or a person's 'I can'.

PMID- 24449289
TI  - Eternal sunshine of the spotless mind? An anthropological-ethical framework for
      understanding and dealing with sexuality in dementia care.
AB  - Contemporary bioethics pays considerable attention to the ethical aspects of
      dementia care. However, ethical issues of sexuality especially as experienced by
      institutionalized persons with dementia are often overlooked. The relevant
      existing ethics literature generally applies an implicit philosophical
      anthropology that favors the principle of respect for autonomy and the
      concomitant notion of informed consent. In this article we will illustrate how
      this way of handling the issue fails in its duty to people with dementia. Our
      thesis is that a more inclusive philosophical anthropology is needed that also
      heeds the fate of this growing population. Drawing on the tradition of
      phenomenology, we will chalk out an anthropological framework that rests on four
      fundamental characteristics of human existence: the decentered self, human
      embodiment, being-in-the-world and being-with-others. Our aim in this article is
      thus to tentatively put forward a broader perspective for looking at aged
      sexuality in institutionalized people with dementia. Hopefully the developed
      framework will mark the beginning of a new and refreshed ethical reflection on
      the topic at hand. 

PMID- 24449290
TI  - Are physicians' estimations of future events value-impregnated? Cross-sectional
      study of double intentions when providing treatment that shortens a dying
      patient's life.
AB  - The aim of the present study was to corroborate or undermine a previously
      presented conjecture that physicians' estimations of others' opinions are
      influenced by their own opinions. We used questionnaire based cross-sectional
      design and described a situation where an imminently dying patient was provided
      with alleviating drugs which also shortened life and, additionally, were intended
      to do so. We asked what would happen to physicians' own trust if they took the
      action described, and also what the physician estimated would happen to the
      general publics' trust in health services. Decrease of trust was used as
      surrogate for an undesirable action. The results are presented as proportions
      with a 95 % Confidence Interval (CI). Statistical analysis was based on inter
      rater agreement (Weighted Kappa)-test as well as chi (2) test and Odds Ratio with
      95 % CI. We found a moderate inter-rater agreement (Kappa = 0.552) between what
      would happen with the physicians' own trust in healthcare and their estimations
      of what would happen with the general population's trust. We identified a
      significant difference between being pro et contra the treatment with double
      intentions and the estimation of the general population's trust (chi(2) = 72, df
      = 2 and p < 0.001). Focusing on either decreasing or increasing own trust and
      being pro or contra the action we identified a strong association [OR 79 (CI 25
      253)]. Although the inter-rater agreement in the present study was somewhat
      weaker compared to a study about the explicit use of the term 'physicians
      assisted suicide' we found that our hypothesis-physicians' estimations of others'
      opinions are influenced by their own opinions-was corroborated. This might have
      implications in research as well as in clinical decision-making. We suggest that
      Merton's ideal of disinterestedness should be highlighted.

PMID- 24449291
TI  - Bone responses to zirconia implants with a thin carbonate-containing
      hydroxyapatite coating using a molecular precursor method.
AB  - Thin carbonate-containing hydroxyapatite (CA) films coating partially stabilized
      zirconia (Y-TZP) were prepared (CA-Y-TZP) to establish a metal-free implant
      system. CA was coated using a molecular precursor method. The CA film was
      deposited on the surface of Y-TZP using a precursor solution, which was a mixture
      of a calcium-ethylenediaminetetraacetic acid (EDTA) complex and phosphate
      compounds. The deposited CA film was characterized by X-ray diffraction, Fourier
      transform infrared spectroscopy, and energy dispersive X-ray spectroscopy
      measurements. A focus ion beam system technique revealed that the thickness of
      the CA film was less than 1.0 um. Biological evaluations of CA-Y-TZP were
      performed by immersion experiments in simulated body fluid (SBF) and implantation
      experiments in the tibiae and femoral condyles of rabbits. In the SBF immersion
      experiment, apatite deposition progressed more on CA-Y-TZP at the early stage of
      immersion than on Y-TZP without the CA coating. Animal experiments revealed that
      bone formation on CA-Y-TZP was similar with than on Y-TZP. Histomorphometrical
      evaluations showed a significantly higher bone-to-implant contact ratio and bone
      mass on CA-Y-TZP after implantation into the femoral trabecular bone of rabbits.
      Therefore, CA-Y-TZP appears to be applicable as a metal-free implant.

PMID- 24449292
TI  - Smoking rates fall among Indian men and rise among women, finds study.

PMID- 24449295
TI  - Portrait of H. H. Thyssen-Bornemisza (Man in a Chair): Lucian Freud.

PMID- 24449296
TI  - Public health officials mark 50th year of measles vaccine: concern remains about
      outbreaks in pockets of unvaccinated.

PMID- 24449297
TI  - FDA moves to curb antibiotic use in livestock.

PMID- 24449298
TI  - Report: States may be unprepared to manage infectious disease threats.

PMID- 24449300
TI  - Gastroesophageal reflux symptoms abate when smoking stops.

PMID- 24449301
TI  - Multivitamins offer no protection to brains or hearts.

PMID- 24449302
TI  - Resuming warfarin after GI bleeding leads to better outcomes.

PMID- 24449303
TI  - Lung cancers overdiagnosed with low-dose CT.

PMID- 24449310
TI  - The accelerated approval of oncologic drugs: lessons from ponatinib.

PMID- 24449311
TI  - Improving the drug development process: more not less randomized trials.

PMID- 24449312
TI  - A piece of my mind. Time to get over it.

PMID- 24449313
TI  - Opening the FDA black box.

PMID- 24449314
TI  - Will detection of microRNA biomarkers in blood improve the diagnosis and survival
      of patients with pancreatic cancer?

PMID- 24449315
TI  - Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005
      2012.
AB  - IMPORTANCE: Many patients and physicians assume that the safety and effectiveness
      of newly approved therapeutic agents is well understood; however, the strength of
      the clinical trial evidence supporting approval decisions by the US Food and Drug
      Administration (FDA) has not been evaluated. OBJECTIVES: To characterize pivotal
      efficacy trials (clinical trials that serve as the basis of FDA approval) for
      newly approved novel therapeutic agents. DESIGN AND SETTING: Cross-sectional
      analysis using publicly available FDA documents for all novel therapeutic agents
      approved between 2005 and 2012. MAIN OUTCOMES AND MEASURES: Pivotal efficacy
      trials were classified according to the following design features: randomization,
      blinding, comparator, and trial end point. Surrogate outcomes were defined as any
      end point using a biomarker expected to predict clinical benefit. The number of
      patients, trial duration, and trial completion rates were also determined.
      RESULTS: Between 2005 and 2012, the FDA approved 188 novel therapeutic agents for
      206 indications on the basis of 448 pivotal efficacy trials. The median number of
      pivotal trials per indication was 2 (interquartile range, 1-2.5), although 74
      indications (36.8%) were approved on the basis of a single pivotal trial. Nearly
      all trials were randomized (89.3% [95% CI, 86.4%-92.2%]), double-blinded (79.5%
      [95% CI, 75.7%-83.2%]), and used either an active or placebo comparator (87.1%
      [95% CI, 83.9%-90.2%]). The median number of patients enrolled per indication
      among all pivotal trials was 760 (interquartile range, 270-1550). At least 1
      pivotal trial with a duration of 6 months or greater supported the approval of 68
      indications (33.8% [95% CI, 27.2%-40.4%]). Pivotal trials using surrogate end
      points as their primary outcome formed the exclusive basis of approval for 91
      indications (45.3% [95% CI, 38.3%-52.2%]), clinical outcomes for 67 (33.3% [95%
      CI, 26.8%-39.9%]), and clinical scales for 36 (17.9% [95% CI, 12.6%-23.3%]).
      Trial features differed by therapeutic and indication characteristics, such as
      therapeutic area, expected length of treatment, orphan status, and accelerated
      approval. CONCLUSIONS AND RELEVANCE: The quality of clinical trial evidence used
      by the FDA as the basis for recent approvals of novel therapeutic agents varied
      widely across indications. This variation has important implications for patients
      and physicians as they make decisions about the use of newly approved therapeutic
      agents.

PMID- 24449316
TI  - Scientific and regulatory reasons for delay and denial of FDA approval of initial
      applications for new drugs, 2000-2012.
AB  - IMPORTANCE: Some new drug applications fail because of inadequate drug
      performance and others are not approved because the information submitted to the
      US Food and Drug Administration (FDA) is unsatisfactory to make that
      determination. Resubmission of failed applications is costly, delaying marketing
      approval and the availability of new drugs to patients. OBJECTIVE: To identify
      the reasons that FDA marketing approval for new drugs was delayed or denied.
      DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of FDA documents and
      extraction of data were performed. We examined all drug applications first
      submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs),
      which are active ingredients never before marketed in the United States in any
      form. Using FDA correspondence and reviews, we investigated the reasons NMEs
      failed to obtain FDA approval. MAIN OUTCOMES AND MEASURES: Reasons for delayed
      FDA approval or nonapproval of NME applications. RESULTS: Of the 302 identified
      NME applications, 151 (50%) were approved when first submitted and 222 (73.5%)
      were ultimately approved. Seventy-one applications required 1 or more
      resubmissions before approval, with a median delay to approval of 435 days
      following the first unsuccessful submission. Of the unsuccessful first-time
      applications, 24 (15.9%) included uncertainties related to dose selection, 20
      (13.2%) choice of study end points that failed to adequately reflect a clinically
      meaningful effect, 20 (13.2%) inconsistent results when different end points were
      tested, 17 (11.3%) inconsistent results when different trials or study sites were
      compared, and 20 (13.2%) poor efficacy when compared with the standard of care.
      The frequency of safety deficiencies was similar among never-approved drugs
      compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37
      of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.05%];
      P = .87). However, efficacy deficiencies were significantly more frequent among
      the never-approved drugs than among those with delayed approvals (61 of 80 never
      approved [76.3%] vs 28 of 71 eventually approved [39.4%]; difference, 36.9% [95%
      CI, 20.25% to 50.86%]; P < .001). CONCLUSIONS AND RELEVANCE: Several potentially
      preventable deficiencies, including failure to select optimal drug doses and
      suitable study end points, accounted for significant delays in the approval of
      new drugs. Understanding the reasons for previous failures is helpful to improve
      the efficiency of clinical development for new drugs.

PMID- 24449317
TI  - FDA approval of cardiac implantable electronic devices via original and
      supplement premarket approval pathways, 1979-2012.
AB  - IMPORTANCE: The US Food and Drug Administration (FDA) evaluates high-risk medical
      devices such as cardiac implantable electronic devices (CIEDs), including
      pacemakers, implantable cardioverter-defibrillators, and cardiac
      resynchronization therapy devices, via the premarket approval (PMA) process,
      during which manufacturers submit clinical data demonstrating safety and
      effectiveness. Subsequent changes to approved high-risk devices are implemented
      via "supplements," which may not require additional clinical testing. OBJECTIVE:
      To characterize the prevalence and characteristics of changes to CIEDs made
      through the PMA supplement process. DESIGN: Using the FDA's PMA database, we
      reviewed all CIEDs approved as original PMAs or supplements from 1979 through
      2012. For each supplement, we collected the date approved, type of supplement
      (panel-track, 180-day, real-time, special, and 30-day notice), and the nature of
      the changes. We calculated the number of supplements approved per PMA and
      analyzed trends relating to different supplement regulatory categories over time.
      For supplements approved via the 180-day regulatory pathway, which often involve
      significant design changes, from 2010-2012, we identified how often additional
      clinical data were collected. RESULTS: From 1979-2012, the FDA approved 77
      original and 5829 supplement PMA applications for CIEDs, with a median of 50
      supplements per original PMA (interquartile range [IQR], 23-87). Excluding
      manufacturing changes that do not alter device design, the number of supplements
      approved each year was stable around a mean (SD) of 2.6 (0.9) supplements per PMA
      per year. Premarket approvals remained active via successive supplements over a
      median period of 15 years (IQR, 8-20), and 79% of the 77 original PMAs approved
      during our study period were the subject of at least 1 supplement in 2012. Thirty
      seven percent of approved supplements involved a change to the device's design.
      Among 180-day supplements approved from 2010-2012, 23% (15/64) included new
      clinical data to support safety and effectiveness. CONCLUSIONS AND RELEVANCE:
      Many CIED models currently used by clinicians were approved via the PMA
      supplement process, not as original PMAs. Most new device models are deemed safe
      and effective without requiring new clinical data, reinforcing the importance of
      rigorous postapproval surveillance of these devices.

PMID- 24449318
TI  - MicroRNA biomarkers in whole blood for detection of pancreatic cancer.
AB  - IMPORTANCE: Biomarkers for the early diagnosis of patients with pancreatic cancer
      are needed to improve prognosis. OBJECTIVES: To describe differences in microRNA
      expression in whole blood between patients with pancreatic cancer, chronic
      pancreatitis, and healthy participants and to identify panels of microRNAs for
      use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19
      9). DESIGN, SETTING, AND PARTICIPANTS: A case-control study that included 409
      patients with pancreatic cancer and 25 with chronic pancreatitis who had been
      included prospectively in the Danish BIOPAC (Biomarkers in Patients with
      Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as
      healthy participants. The microRNA expressions in pretreatment whole blood RNA
      samples were collected and analyzed in 3 randomly determined subcohorts:
      discovery cohort (143 patients with pancreatic cancer, 18 patients with chronic
      pancreatitis, and 69 healthy participants), training cohort (180 patients with
      pancreatic cancer, 1 patient with chronic pancreatitis, and 199 healthy
      participants), and validation cohort (86 patients with pancreatic cancer, 7
      patients with chronic pancreatitis, and 44 healthy participants); 754 microRNAs
      were screened in the discovery cohort and 38 microRNAs in the training cohort and
      13 microRNAs in the validation cohort. MAIN OUTCOMES AND MEASURES: Identification
      of microRNA panels (classifiers) for diagnosing pancreatic cancer. RESULTS: The
      discovery cohort demonstrated that 38 microRNAs in whole blood were significantly
      dysregulated in patients with pancreatic cancer compared with controls. These
      microRNAs were tested in the training cohort and 2 diagnostic panels were
      constructed comprising 4 microRNAs in index I (miR-145, miR-150, miR-223, miR
      636) and 10 in index II (miR-26b, miR-34a, miR-122, miR-126*, miR-145, miR-150,
      miR-223, miR-505, miR-636, miR-885.5p). The test characteristics for the training
      cohort were index I area under the curve (AUC) of 0.86 (95% CI, 0.82-0.90),
      sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.64 (95% CI, 0.57
      0.71); index II AUC of 0.93 (95% CI, 0.90-0.96), sensitivity of 0.85 (95% CI,
      0.79-0.90), and specificity of 0.85 (95% CI, 0.80-0.85); and CA19-9 AUC of 0.90
      (95% CI, 0.87-0.94), sensitivity of 0.86 (95% CI, 0.80-0.90), and specificity of
      0.99 (95% CI, 0.96-1.00). Performances were strengthened in the validation cohort
      by combining panels and CA19-9 (index I AUC of 0.94 [95% CI, 0.90-0.98] and index
      II AUC of 0.93 [95% CI, 0.89-0.97]). Compared with CA19-9 alone, the AUC for the
      combination of index I and CA19-9 was significantly higher (P = .01). The
      performance of the panels in patients with stage IA-IIB pancreatic cancer was
      index I AUC of 0.80 (95% CI, 0.73-0.87); index I and CA19-9 AUC of 0.83 (95% CI,
      0.76-0.90); index II AUC of 0.91 (95% CI, 0.87-0.94); and index II and CA19-9 AUC
      of 0.91 (95% CI, 0.86-0.95). CONCLUSIONS AND RELEVANCE: This study identified 2
      diagnostic panels based on microRNA expression in whole blood with the potential
      to distinguish patients with pancreatic cancer from healthy controls. Further
      research is necessary to understand whether these have clinical implications for
      early detection of pancreatic cancer and how much this information adds to serum
      CA19-9.

PMID- 24449319
TI  - How to use a subgroup analysis: users' guide to the medical literature.
AB  - Clinicians, when trying to apply trial results to patient care, need to
      individualize patient care and, potentially, manage patients based on results of
      subgroup analyses. Apparently compelling subgroup effects often prove spurious,
      and guidance is needed to differentiate credible from less credible subgroup
      claims. We therefore provide 5 criteria to use when assessing the validity of
      subgroup analyses: (1) Can chance explain the apparent subgroup effect; (2) Is
      the effect consistent across studies; (3) Was the subgroup hypothesis one of a
      small number of hypotheses developed a priori with direction specified; (4) Is
      there strong preexisting biological support; and (5) Is the evidence supporting
      the effect based on within- or between-study comparisons. The first 4 criteria
      are applicable to individual studies or systematic reviews, the last only to
      systematic reviews of multiple studies. These criteria will help clinicians
      deciding whether to use subgroup analyses to guide their patient care. 

PMID- 24449320
TI  - Exercise-induced leg pain and high blood pressure.

PMID- 24449321
TI  - Association of Mediterranean diet with peripheral artery disease: the PREDIMED
      randomized trial.

PMID- 24449322
TI  - Hormone therapy use and outcomes in the Women's Health Initiative trials.

PMID- 24449323
TI  - Hormone therapy use and outcomes in the Women's Health Initiative trials--reply.

PMID- 24449324
TI  - Prevention and control of hypertension in different countries.

PMID- 24449325
TI  - Prevention and control of hypertension in different countries--reply.

PMID- 24449326
TI  - Patient-reported outcome alert monitoring.

PMID- 24449329
TI  - New drugs-miracles or mirages?

PMID- 24449327
TI  - Patient-reported outcome alert monitoring--reply.

PMID- 24449330
TI  - JAMA patient page. FDA authorization of medical devices.

PMID- 24449331
TI  - Best targeted sarcoma treatment: advances from the Musculoskeletal Tumor Society
      annual meeting.

PMID- 24449333
TI  - Ecogeographical and phylogenetic effects on craniofacial variation in macaques.
AB  - The widespread and complex ecogeographical diversity of macaques may have caused
      adaptive morphological convergence among four phylogenetic subgroups, making
      their phylogenetic relationships unclear. We used geometric morphometrics and
      multivariate analyses to test the null hypothesis that craniofacial morphology
      does not vary with ecogeographical and phylogenetic factors. As predicted by
      Bergmann's rule, size was larger for the fascicularis and sinica groups in colder
      environments. No clear size cline was observed in the silenus and sylvanus
      groups. An allometric pattern was observed across macaques, indicating that as
      size increases, rounded faces become more elongated. However, the elevation was
      differentiated within each of the former two groups and between the silenus and
      sylvanus groups, and the slope decreased in each of the two northern species of
      the fascicularis group. All allometric changes resulted in the similar situation
      of the face being more rounded in animals inhabiting colder zones and/or in
      animals having a larger body size than that predicted from the overarching
      allometric pattern. For non-allometric components, variations in prognathism were
      significantly correlated with dietary differences; variations in localized shape
      components in zygomatics and muzzles were significantly correlated with
      phylogenetic differences among the subgroups. The common allometric pattern was
      probably influenced directly or indirectly by climate-related factors, which are
      pressures favoring a more rounded face in colder environments and/or a more
      elongated face in warmer environments. Allometric dissociation could have
      occurred several times in Macaca even within a subgroup because of their wide
      latitudinal distributions, critically impairing the taxonomic utility of
      craniofacial elongation.

PMID- 24449332
TI  - Acetabular component thickness does not affect mid-term clinical results in hip
      resurfacing.
AB  - BACKGROUND: The benefits of using thin acetabular components for hip resurfacing
      have been shown in terms of bone conservation, but there currently are little
      data available in the literature addressing the mid-term clinical results of
      these devices. QUESTIONS/PURPOSES: We aimed to determine whether thinner
      acetabular components altered mid-term postoperative clinical scores,
      complication rates, survivorship, radiographic appearance, and metal ion levels.
      METHODS: Two hundred eighty-one patients with unilateral disease received a 5-mm
      thick acetabular shell and 223 received a 3.5-mm shell. The femoral component
      implanted in both groups was identical. We compared clinical scores, complication
      rates, survivorship, radiographic results, and ion levels between these two
      groups. RESULTS: UCLA hip scores were similar (pain, p = 0.0976; walking, p =
      0.9571; function, p = 0.9316; activity, p = 0.2085). Complications were higher in
      the 5-mm group (6.4% versus 1.8%, p = 0.0431). Both groups were similar regarding
      survivorship (p = 0.3181), cup radiolucency at 5 years (p = 0.107), and metal ion
      levels (cobalt p = 0.404, chromium p = 0.250). CONCLUSIONS: With comparable mid
      term clinical results, there is no tangible reason to abstain from using the 3.5
      mm acetabular component. LEVEL OF EVIDENCE: Level III, retrospective comparative
      study. See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 24449334
TI  - Power motion-mode Doppler signature: a useful tool for assessing middle cerebral
      artery stenosis.
AB  - PURPOSE: To identify power motion-mode Doppler (PMD) patterns and assess their
      diagnostic value for the diagnosis of middle cerebral artery (MCA) stenosis.
      METHODS: Retrospective analyses of PMD data were performed for the identification
      of specific patterns related to MCA stenosis. The interrater reliability and the
      validity of these patterns were studied, using magnetic resonance angiography and
      conventional transcranial Doppler sonography as gold standards. RESULTS: Three
      PMD patterns were identified: the so-called black-hole, the white-hole, and the
      diastolic-band patterns in 58 among 178 MCAs. The mean flow velocity was
      significantly higher in arterial segments with the black-hole patterns and lower
      in segments with the diastolic-band pattern compared with the segments with
      normal patterns. The interrater reliability was good for each pattern. The black
      hole pattern or its combination with the white-hole pattern showed the highest
      validity. CONCLUSION: Despite some limitations, the black-hole PMD pattern or its
      combination with the white-hole pattern appeared as a reliable and valid marker
      for the diagnosis of MCA stenosis.

PMID- 24449335
TI  - Hypertrophic cardiomyopathy in cardiac CT: a validation study on the detection of
      intramyocardial fibrosis in consecutive patients.
AB  - Hypertrophic Cardiomyopathy (HCM) confers a 4-5 %/year-risk for sudden cardiac
      death. Intramyocardial fibrosis (IF) is associated with this risk. The gold
      standard of IF visualization is cardiovascular magnetic resonance (CMR) with late
      gadolinium enhancement (LGE-CMR). In view of a number of CMR-limitations the
      hypothesis of this study was that late enhanced multi-slice computed tomography
      (leMDCT) enables demonstration of late enhancement (LE) indicating IF. In a
      prospective single-center validation study leMDCT research-scans were exclusively
      performed for IF-imaging in HCM-patients not including non-invasive coronary
      angiography during first-pass (64-slice; 80 kV; Iopromide, 150 mL, injected 7 min
      before scanning). Applying a 17-segment-polar-map short cardiac axis views
      (multiplanar reformations; 5 mm slice thickness) were analysed in order to
      exclude/detect, localize and measure LE practicing the manual quantification
      method if present. Finally, leMDCT and LGE-CMR data were unblinded for intermodal
      correlation. We included n = 24 patients consecutively (64.0 +/- 14.5 years of
      age). LE was demonstrated by LGE-CMR in n = 14/24 patients (prevalence 58 %).
      Patient- and segment-based sensitivity in leMDCT was 100 and 68 %, respectively.
      In leMDCT tissue density of LE was 142 +/- 51 versus 89.9 +/- 19.3 HU in remote
      myocardium (p < 0.001). Signal-to-noise-ratio (SNR) and contrast-to-noise-ratio
      (CNR) appeared to be 7.3 +/- 3.3 and 2.3 +/- 1, respectively. Sizing of LE-area
      gave 2.2 +/- 1.4 cm(2) in leMDCT versus 2.9 +/- 2.4 cm(2) in LGE-CMR (r = 0.93).
      Intra-/interobserver variability was assessed with an accuracy of 0.36 cm(2) (r =
      0.91) and 0.47 cm(2) (r = 0.82), respectively. In consecutive HCM patients leMDCT
      can reliably detect intramyocardial fibrosis marked by LE. In view of a
      comparatively low SNR and CNR leMDCT may alternatively be applied in case of CMR
      contraindications.

PMID- 24449337
TI  - Carbon-coated LiTi(2)(PO(4))(3) : an ideal insertion host for lithium-ion and
      sodium-ion batteries.
AB  - We report the extraordinary performance of carbon-coated sodium super ion
      conductor (NASICON)-type LiTi2 (PO4 )3 as an ideal host matrix for reversible
      insertion of both Li and Na ions. The NASICON-type compound was prepared by means
      of a Pechini-type polymerizable complex method and was subsequently carbon
      coated. Several characterization techniques such as XRD, thermogravimetric
      analysis (TGA), field-emission (FE) SEM, TEM, and Raman analysis were used to
      study the physicochemical properties. Both guest species underwent a two-phase
      insertion mechanism during the charge/discharge process that was clearly
      evidenced from galvanostatic and cyclic voltammetric studies. Unlike that of Li
      (~1.5 moles of Li), Na insertion exhibits better reversibility (~1.59 moles of
      Na) while experiencing a slightly higher capacity fade (~8 % higher than Li) and
      polarization (780 mV) than Li. However, excellent rate capability profiles were
      noted for Na insertion relative to its counterpart Li. Overall, the Na insertion
      properties were found to be superior relative to Li insertion, which makes carbon
      coated NASICON-type LiTi2 (PO4 )3 hosts attractive for the development of next
      generation batteries. 

PMID- 24449336
TI  - A fast and effective method to assess myocardial hyperemia in acute myocarditis
      by magnetic resonance.
AB  - Current cardiac magnetic resonance (CMR) quantitative signs for the diagnosis of
      myocarditis include myocardial edema, fibrosis and myocardial hyperemia (Hyp).
      Methods for the assessment of Hyp are actually complex and time-consuming. To
      test a simple and fast method to assess Hyp, using contrast enhancement steady
      state free precession (ceSSFP) technique. CMR imaging at 1.5T was performed on 39
      patients with diagnosis of acute myocarditis and in 20 healthy controls. Hyp was
      evaluated in systolic and diastolic frames (Hyp-SYS and Hyp-DIA) as areas of
      myocardial hyperintensity in ceSSFP images early after gadolinium injection.
      Myocardial edema was evaluated using T2-STIR images. Myocardial fibrosis was
      assessed in conventional late gadolinium enhancement (LGE) images. A value of
      <=12.1 g of Hyp-DIA was obtained as cut-off of normality in healthy controls.
      Using this threshold, Hyp was detected in 30 patients (77 %) with myocarditis.
      LGE was detected in 36 patients (92 %), and myocardial edema in 38 (97 %)
      patients with myocarditis A linear relation was found between Hyp-DIA and the
      extent of myocardial edema (R(2) 0.48, 95 % CI 0.47-0.85, p < 0.001) and the
      extent of LGE (R(2) 0.41, 95 % CI 0.31-0.61, p < 0.001). Patients with hyperemia
      had higher levels of C-reactive protein (p < 0.001), a higher extent of LGE (p <
      0.05) and a larger left atrial area (p < 0.05). ceSSFP sequence at CMR is a novel
      and fast method to assess myocardial hyperemia in patient with acute myocarditis.
      Compared with non-Hyp subjects, patients with Hyp had more signs of inflammation
      and myocardial damage.

PMID- 24449338
TI  - Smoking is not associated with autoantibody production in systemic lupus
      erythematosus patients, unaffected first-degree relatives, nor healthy controls.
AB  - OBJECTIVE: The objective of this paper is to examine whether smoking is
      associated with autoantibody production in systemic lupus erythematosus (SLE)
      patients, unaffected first-degree relatives (FDR) of individuals with SLE--a
      group at increased risk of developing SLE--or unaffected, unrelated controls.
      METHODS: Detailed demographic, environmental, clinical, and therapeutic
      information was collected by questionnaire on 1242 SLE patients, 981 FDRs, and
      946 controls in the Lupus Family Registry and Repository; a blood sample was
      obtained. All sera were tested for multiple lupus autoantibodies by
      immunofluorescence and luminex bead-based assays. Generalized estimating
      equations, adjusting for age, gender, and ethnicity and accounting for
      correlation within families, were used to assess smoking status with the
      dichotomous outcome variables of positivity for SLE status, positivity of ANA by
      immunofluorescence (>=1:120), positivity for >=1 autoantibody by the luminex
      assay, and positivity for each of the 11 autoantibodies. RESULTS: Current smoking
      was associated with being positive for >=1 autoantibody (excluding ANA) (adjusted
      OR = 1.53, 95% CI 1.04-2.24) in our subjects with SLE. No association was
      observed in unaffected FDRs or healthy controls. Former smoking was associated
      with anti-Ro/SS-A60 in our unaffected FDRs. There was an increased association
      with anti-nRNP A seropositivity, as well as a decreased association with anti
      nRNP 68 positivity, in current smokers in SLE subjects. CONCLUSIONS: No clear
      association between smoking status and individual autoantibodies was detected in
      SLE patients, unaffected FDRs, nor healthy controls within this collection. The
      association of smoking with SLE may therefore manifest its risk through
      mechanisms outside of autoantibody production, at least for the specificities
      tested.

PMID- 24449339
TI  - Proximity-enabled protein crosslinking through genetically encoding haloalkane
      unnatural amino acids.
AB  - The selective generation of covalent bonds between and within proteins would
      provide new avenues for studying protein function and engineering proteins with
      new properties. New covalent bonds were genetically introduced into proteins by
      enabling an unnatural amino acid (Uaa) to selectively react with a proximal
      natural residue. This proximity-enabled bioreactivity was expanded to a series of
      haloalkane Uaas. Orthogonal tRNA/synthetase pairs were evolved to incorporate
      these Uaas, which only form a covalent thioether bond with cysteine when
      positioned in close proximity. By using the Uaa and cysteine, spontaneous
      covalent bond formation was demonstrated between an affibody and its substrate Z
      protein, thereby leading to irreversible binding, and within the affibody to
      increase its thermostability. This strategy of proximity-enabled protein
      crosslinking (PEPC) may be generally expanded to target different natural amino
      acids, thus providing diversity and flexibility in covalent bond formation for
      protein research and protein engineering. 

PMID- 24449340
TI  - The development of copper-catalyzed aerobic oxidative coupling of H-tetrazoles
      with boronic acids and an insight into the reaction mechanism.
AB  - The development of a highly efficient and practical protocol for the direct C-N
      coupling of H-tetrazole and boronic acid was presented. A careful and patient
      optimization of a variety of reaction parameters revealed that this
      conventionally challenge reaction could indeed proceed efficiently in a very
      simple system, that is, just by stirring the tetrazoles and boronic acids under
      oxygen in the presence of different Cu(I) or Cu(II) salts with only 5 mol %
      loading in DMSO at 100  degrees C. Most significantly, the reaction could proceed
      very smoothly in a regiospecific manner to afford the 2,5-disubstituted
      tetrazoles in high to excellent yields. A mechanistic study revealed that both
      tetrazole and DMSO are crucial for the generation of catalytically active copper
      species in the reaction process in addition to their role as reactant and
      solvent, respectively. It is demonstrated that in the reaction cycle, the Cu(I)
      catalyst could be oxidized to Cu(II) by oxygen to form a [CuT2D] complex (T =
      tetrazole anion; D = DMSO) through an oxidative copper amination reaction. The
      Cu(II) complex thus formed was confirmed to be the real catalytically active
      copper species. Namely, the Cu(II) complex disproportionates to aryl Cu(III) and
      Cu(I) in the presence of boronic acid. Facile elimination of the Cu(III) species
      delivers the C-N-coupled product. The results presented herein not only provide a
      reliable and efficient protocol for the synthesis of 2,5-disubstituted
      tetrazoles, but most importantly, the mechanistic results would have broad
      implications for the de novo design and development of new methods for Cu
      catalyzed coupling reactions.

PMID- 24449342
TI  - Disrupted brain anatomical connectivity in medication-naive patients with first
      episode schizophrenia.
AB  - Previous studies suggested that the topological properties of brain anatomical
      networks may be aberrant in schizophrenia (SCZ), and most of them focused on the
      chronic and antipsychotic-medicated SCZ patients which may introduce various
      confounding factors due to antipsychotic medication and duration of illness. To
      avoid those potential confounders, a desirable approach is to select medication
      naive, first-episode schizophrenia (FE-SCZ) patients. In this study, we acquired
      diffusion tensor imaging datasets from 30 FE-SCZ patients and 34 age- and gender
      matched healthy controls. Taking a distinct gray matter region as a node, inter
      regional connectivity as edge and the corresponding streamline counts as edge
      weight, we constructed whole-brain anatomical networks for both groups,
      calculated their topological parameters using graph theory, and compared their
      between-group differences using nonparametric permutation tests. In addition,
      network-based statistic method was utilized to identify inter-regional
      connections which were impaired in the FE-SCZ patients. We detected only
      significantly decreased inter-regional connections in the FE-SCZ patients
      compared to the controls. These connections were primarily located in the
      frontal, parietal, occipital, and subcortical regions. Although small-worldness
      was conserved in the FE-SCZ patients, we found that the network strength and
      global efficiency as well as the degree were significantly decreased, and
      shortest path length was significantly increased in the FE-SCZ patients compared
      to the controls. Most of the regions that showed significantly decreased nodal
      parameters belonged to the top-down control, sensorimotor, basal ganglia, and
      limbic-visual system systems. Correlation analysis indicated that the nodal
      efficiency in the sensorimotor system was negatively correlated with the severity
      of psychosis symptoms in the FE-SCZ patients. Our results suggest that the
      network organization is changed in the early stages of the SCZ disease process.
      Our findings provide useful information for further understanding the brain white
      matter dysconnectivity of schizophrenia. 

PMID- 24449341
TI  - A rapid fluorescence polarization-based method for genotypic detection of drug
      resistance in Mycobacterium tuberculosis.
AB  - Rapid detection of drug-resistant Mycobacterium tuberculosis is critical to the
      effective early treatment and prevention of the transmission of tuberculosis.
      However, conventional drug susceptibility tests for M. tuberculosis require up to
      several weeks. In the present study, the One Label Extension genotyping method
      was adapted for rapid detection of drug resistance-associated sequence variations
      in six genes of M. tuberculosis, viz. rpoB, rpsL, rrs, embB, katG, or inhA. The
      method utilizes polymerase chain reaction amplified fragments of the drug
      resistant genes as reaction templates, and proceeds with template-directed primer
      extension incorporating a fluorescence-labeled nucleotide, which is then measured
      by fluorescence polarization. A total of 121 M. tuberculosis isolates from
      clinical sputum specimens were examined by this genotyping method and verified by
      direct sequencing of polymerase chain reaction amplicons harboring previously
      reported mutational sites associated with M. tuberculosis drug resistance. Based
      on phenotyping results obtained from microbiology-based drug susceptibility
      tests, the sensitivity, specificity, and test efficiency estimated for One Label
      Extension assays were respectively 83.9 %, 95.5 %, and 92.4 % with ropB in
      rifampin resistance, 67.3 %, 97.1 %, and 84.3 % with rpsL and rrs in streptomycin
      resistance, 60.0 %, 96.0 %, and 91.4 % with embB in ethambutol resistance, 68.4
      %, 94.9 %, and 86.3 % with inhA and katG in isoniazid resistance, and 74.1 %,
      98.9 %, and 93.2 % in multiple drug resistance defined as resistance to at least
      both isoniazid and rifampin. In conclusion, examination of clinical sputum
      specimens by One Label Extension based genotyping provides a valid method for the
      rapid molecular detection of drug-resistant M. tuberculosis. 

PMID- 24449343
TI  - Proteomic analysis of human substantia nigra identifies novel candidates involved
      in Parkinson's disease pathogenesis.
AB  - Parkinson's disease (PD) pathology spreads throughout the brain following a
      region-specific process predominantly affecting the substantia nigra (SN) pars
      compacta. SN exhibits a progressive loss of dopaminergic neurons responsible for
      the major cardinal motor symptoms, along with the occurrence of Lewy bodies in
      the surviving neurons. To gain new insights into the underlying pathogenic
      mechanisms in PD, we studied postmortem nigral tissues dissected from
      pathologically confirmed PD cases (n = 5) and neurologically intact controls (n =
      8). Using a high-throughput shotgun proteomic strategy, we simultaneously
      identified 1795 proteins with concomitant quantitative data. To date, this
      represents the most extensive catalog of nigral proteins. Of them, 204 proteins
      displayed significant expression level changes in PD patients versus controls.
      These were involved in novel or known pathogenic processes including
      mitochondrial dysfunction, oxidative stress, or cytoskeleton impairment. We
      further characterized four candidates that might be relevant to PD pathogenesis.
      We confirmed the differential expression of ferritin-L and seipin by Western blot
      and demonstrated the neuronal localization of gamma glutamyl hydrolase and
      nebulette by immunohistochemistry. Our preliminary findings suggest a role for
      nebulette overexpression in PD neurodegeneration, through mechanisms that may
      involve cytoskeleton dynamics disruption. All MS data have been deposited in the
      ProteomeXchange with identifier PXD000427
      (http://proteomecentral.proteomexchange.org/dataset/PXD000427). 

PMID- 24449344
TI  - Brief report: importance of SOX8 for in vitro chondrogenic differentiation of
      human mesenchymal stromal cells.
AB  - The transcription factor SOX9 is believed to be the master regulator of
      chondrogenesis. SOX8 is another SOX group E transcription factor with a high
      degree of homology to SOX9. Here, we demonstrate that SOX8 mRNA levels decrease
      during in vitro dedifferentiation of human articular chondrocytes and increase
      during chondrogenic differentiation of mesenchymal stromal cells. Knockdown of
      SOX9 reduced the expression of SOX8, COL2A1, and a range of other chondrogenic
      molecules. SOX8 knockdown reduced the expression of a large number of overlapping
      chondrogenic molecules, but not SOX9. Neither siSOX9 nor siSOX8 altered
      expression of the hypertrophic marker gene COL10A1. siSOX9, but not siSOX8 led to
      upregulation of hypertrophy associated genes MMP13 and ALPL. Transfection of
      synthetic SOX5, 6, and 9 mRNA trio upregulated SOX8, COL2A1, and ACAN, but not
      COL10A1 mRNA. Replacement of synthetic SOX9 by SOX8 in the SOX trio showed
      similar but lower chondrogenic effect. We conclude that SOX8 expression is
      regulated by SOX9, and that both together with SOX5 and SOX6 are required as a
      SOX quartet for transcription of COL2A1 and a large number of other chondrogenic
      molecules. Neither SOX8 nor SOX9 affect COL10A1 expression, but SOX9 inhibits
      chondrocyte hypertrophy through inhibition of MMP13 and ALPL expression.

PMID- 24449345
TI  - Ribotype 027 Clostridium difficile infections with measurable stool toxin have
      increased lactoferrin and are associated with a higher mortality.
AB  - We evaluated clinical and diagnostic indicators of severe C. difficile infection
      (CDI) and their association with poor clinical outcome. A total of 210 patients
      positive according to PCR (toxin B: tcdB) were included, with patients having a
      median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety
      one percent (n = 191) were positive by toxigenic culture and 61% (n = 129) had
      stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin
      (mean 316 MUg/g versus 106 MUg/g stool; p < 0.0001). Forty percent of patients (n
      = 85) were infected with ribotype 027 and significantly more of these patients
      had measurable stool toxin (79% vs. 50%; p < 0.0001). The mean fecal lactoferrin
      was significantly higher for toxin-positive 027 CDI compared with the 027 toxin
      negative group (317 vs 60 MUg/g; p = 0.0014). Ribotype 027 CDI with stool toxin
      showed a higher all-cause, 100-day mortality compared with non-027 with stool
      toxin (36 % vs 18%; p = 0.017). Logistic regression univariate analysis for odds
      ratio (OR) and p values revealed that age (OR = 1.1), intensive care unit
      treatment (OR = 2.7), CI (OR = 1.2), 027 CDI (OR = 2.1), white blood cell count
      (OR = 1.0), albumin level (OR = 0.1), and stool toxin-positive 027 CDI (OR = 2.5)
      were significantly associated with 100-day mortality (p < 0.05). In conclusion,
      CDI PCR-positive patients with 027 infection and stool toxin have increased
      lactoferrin and are at an increased risk of death.

PMID- 24449346
TI  - Bronchial microbiome of severe COPD patients colonised by Pseudomonas aeruginosa.
AB  - The bronchial microbiome in severe COPD during stability and exacerbation in
      patients chronically colonised by Pseudomonas aeruginosa (PA), has not been
      defined. Our objective was to determine the characteristics of the bronchial
      microbiome of severe COPD patients colonised and not colonised by P. aeruginosa
      and its changes during exacerbation. COPD patients with severe disease and
      frequent exacerbations were categorised according to chronic colonisation by P.
      aeruginosa. Sputum samples were obtained in stability and exacerbation, cultured,
      and analysed by 16S rRNA gene amplification and pyrosequencing. Sixteen patients
      were included, 5 of them showing chronic colonisation by P. aeruginosa.
      Pseudomonas genus had significantly higher relative abundance in stable colonised
      patients (p = 0.019), but no significant differences in biodiversity parameters
      were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1,
      124 (77-159) vs 140 (115-163), p = 0.364). In PA-colonised patients bronchial
      microbiome changed to a microbiome similar to non-PA-colonised patients during
      exacerbations. An increase in the relative abundance over 20 % during
      exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus,
      Neisseria, Achromobacter and Corynebacterium genera, which include recognised
      potentially pathogenic microorganisms, in 13 patients colonised and not colonised
      by P. aeruginosa with paired samples. These increases were not identified by
      culture in 5 out of 13 participants (38.5 %). Stable COPD patients with severe
      disease and PA-colonised showed a similar biodiversity to non-PA-colonised
      patients, with a higher relative abundance of Pseudomonas genus in bronchial
      secretions. Exacerbation in severe COPD patients showed the same microbial
      pattern, independently of previous colonisation by P. aeruginosa.

PMID- 24449347
TI  - Diagnostic value of serum pneumococcal DNA load during invasive pneumococcal
      infections.
AB  - Detection of pneumococcal DNA in blood could be a fast alternative for blood
      culture in invasive pneumococcal disease (IPD). In this study we compared the
      diagnostic value of the serum pneumococcal DNA load between different clinical
      syndromes in adults with bacteremic pneumococcal infections, also after
      initiation of antibiotic treatment. Adults hospitalized with a blood culture
      proven pneumococcal infection between December 2008 and June 2013 were
      retrospectively included. Pneumococcal DNA loads in corresponding serum samples
      were determined by qPCR. Data on clinical diagnosis, course of disease and
      antibiotic treatment were extracted from medical records. For 53 IPD cases
      eligible stored serum samples were retrieved. The proportion of samples positive
      in qPCR was lower in uncomplicated pneumonia compared with other clinical
      syndromes (59.5 % vs. 100 %, p = 0.005). The pneumococcal DNA load was higher in
      cases other than uncomplicated pneumonia (p = 0.043) as well as in more severe
      disease (p-values 0.018, 0.029 and 0.003 for PSI Risk Class IV/V, ICU admission
      and mortality, respectively). Both detection of pneumococcal DNA and distribution
      of load did not significantly change over the first days of hospitalization
      despite treatment with appropriate antibiotics. Detection of pneumococcal DNA in
      serum was more sensitive in clinical syndromes other than uncomplicated
      pneumonia. Furthermore, the pneumococcal DNA load was associated with the type of
      IPD and severity of disease. Since the serum pneumococcal DNA load seemed
      unaffected by antibiotic treatment during the first days of IPD, it may offer an
      alternative for culture methods after prior antibiotic use.

PMID- 24449348
TI  - CD4/CD8 ratio is a promising candidate for non-invasive measurement of liver
      fibrosis in chronic HCV-monoinfected patients.
AB  - The extent of liver fibrosis is an important factor in prognosis and clinical
      decision-making in chronic hepatitis C virus (HCV) infection. We investigated
      CD4/CD8 ratio in HCV-monoinfected and HIV/HCV-coinfected patients, in order to
      reveal its relation with liver fibrosis. CD4/CD8 ratio in the peripheral blood
      was assessed by flow cytometry in a cohort of 19 HCV-monoinfected, 14 HIV/HCV
      coinfected, ten HIV-monoinfected patients and 15 healthy controls. Liver fibrosis
      was assessed by transient elastography (n = 25) or by liver biopsy (n = 8).
      Coinfection with HIV was associated with decreased CD4/CD8 ratios in chronic HCV
      infected patients, despite adequate antiretroviral treatment. Furthermore, HCV
      monoinfected patients with F3-F4 liver fibrosis demonstrated much lower CD4/CD8
      ratios than patients with F0-F2 fibrosis (1.4 versus 2.5, p = 0.023). Similarly,
      we observed a strong negative correlation between the CD4/CD8 ratio and liver
      stiffness measured by transient elastography (R = -0.78, p = 0.0006). ROC
      analysis revealed that CD4/CD8 ratio as a non-invasive marker for fibrosis is
      very promising (area under the curve 0.8). Although our study was performed with
      a relatively small number of patients, our findings suggest that the CD4/CD8
      ratio is a promising candidate for non-invasive evaluation of liver fibrosis in
      HCV-monoinfected patients.

PMID- 24449349
TI  - [Treatment of sepsis and septic shock with immunoglobulins].

PMID- 24449350
TI  - [What are the advantages of the modified Friedewald equation?--Modified Friedwald
      equation measures LDL-cholesterol more exactly].

PMID- 24449351
TI  - [Quality of hospital care in Germany: analysis of the trend between 2004 and 2008
      from external quality assurance data].
AB  - BACKGROUND AND OBJECTIVES: Introducing fixed fees for inpatient hospital care has
      raised fears of a negative influence on treatment quality. To address these
      concerns, an external quality assurance was implemented. The results of the
      quality indicators should indicate changes in the quality of inpatient care
      between 2004 and 2008. METHODS: On the basis of the evaluation data delivered by
      the Federal Quality Assurance Agency, quality indicators with similar results of
      at least 3 subsequent years were included. A trend was identified with linear
      regression as well as with a constant change in the results. 204 quality
      indicators of 19 health care sectors of 6 diagnosis groups were included.
      RESULTS: Half of the quality indicators showed a particularly striking quality
      improvement in the categories "indication" and "process". The lowest number of
      quality indicators with a quality improvement occurred in the cardiac surgery. To
      this diagnosis group also belong 13 of the 18 quality indicators with
      deterioration. Sixteen of the 18 quality indicators rank among the category
      "result". CONCLUSION: The quality of inpatient care improved substantially from
      2004 through 2008, measured against the quality indicators of the external
      comparable quality assurance. This corresponds to other analyses of a similar
      time period in Germany of the same or different data sources. Those analyses
      showed additionally that the subjective perceptions of clinicians and of nursing
      staff are significantly worse.

PMID- 24449352
TI  - [Sialadenoma papilliferum--a rare benign endobronchial tumor].
AB  - HISTORY AND PRESENTATION AT ADMISSION: An 82-year-old male patient presented with
      a 3 week history of exercise-induced dyspnea, productive cough and left sided
      chest pain. INVESTIGATIONS: Computertomography of the chest revealed an occluding
      endobronchial tumor in the left main bronchus with enlarged mediastinal lymph
      nodes, mediastinal shift and post-stenotic peribronchitis. TREATMENT AND COURSE:
      The tumor was removed completely with an optical forceps in rigid bronchoscopy.
      Histologically an endobronchial sialadenoma papilliferum was diagnosed.
      CONCLUSIONS: Benign tumors of the lower airways are rare. They cannot be
      distinguished reliably from malignant tumors by their endoscopic and radiologic
      appearance. Sialadenoma papilliferum is an extremely rare benign salivary gland
      tumor which is characterized by coexisting glandular and (pseudo) papillar
      formations. It occurs mainly in the oral cavity. The relapse rate is 10-15%. In
      single cases a malignant transformation may appear.

PMID- 24449353
TI  - [34-year-old woman with left-sided acute lower abdominal pain].

PMID- 24449354
TI  - [Colorectal cancer].

PMID- 24449355
TI  - [Is there a role for surgery in the treatment of type 2 diabetes?].
AB  - Typ 2 diabetes mellitus (T2DM) can be regarded as a chronic and progressive
      disease which is rapidly increasing worldwide. There is a significant coincidence
      of T2DM and obesity, the latter playing a major role in the development of
      insulin resistance. Medical treatment comprises lifestyle counseling, weight
      management and an increased physical activity, frequently in combination with
      pharmacotherapy. However, especially in obese patients, metabolic aims are
      frequently not achieved which can be attributed to the lack of significant weight
      reduction. Currently, pancreas transplantation plays only a minor role in the
      treatment of patients with T2DM. Bariatric surgery has been proven to be a safe
      and effective therapeutic option in obese patients that leads to a significant
      weight loss. Moreover, in the majority of obese diabetics, a complete or partial
      remission of T2DM is observed. The significant weight loss is associated with
      improved insulin sensitivity. There is some evidence that alterations of gut
      hormones play an additional role in the amelioration of T2DM. However, little is
      known about the long-term effect of bariatric surgery on diabetes remission.
      Bariatric procedures should be considered in obese patients with T2DM (BMI > 35
      kg/m2) and poorly controlled metabolic status. Despite the encouraging results in
      normal weight or overweight patients with T2DM, surgery can not yet be
      recommended in these patients. Intensive research about the impact of bariatric
      surgery on diabetes remission offers a unique opportunity to understand
      pathophysiology of T2DM. Furthermore, it may help to develop less invasive
      interventions and to identify new therapeutic targets for the treatment of T2DM.

PMID- 24449356
TI  - MRI demonstrates a decrease in myocardial infarct healing and increase in
      compensatory ventricular hypertrophy following mechanical microvascular
      obstruction.
AB  - PURPOSE: To provide direct evidence that mechanical obstruction of microvessels
      inhibits infarct resorption (healing) and enhances left ventricular (LV)
      remodeling using MRI. MATERIALS AND METHODS: Animals (n = 20 pigs) served as
      controls (group I) or were subjected to either 90 min left anterior descending
      (LAD) coronary artery occlusion/reperfusion (group II) or 90 min LAD occlusion/
      microemboli delivery/reperfusion (group III). MRI (cine and delayed contrast
      enhanced MRI, DE-MRI) was performed at 3 days and 5 weeks after interventions and
      used for assessing LV function, mass, and extent of myocardial damage and
      microvascular obstruction (MVO) using semi-automated threshold method. RESULTS:
      Persistent MVO in the core of contiguous infarct was larger and more frequent (n
      = 8/8) in group III than group II (4/8) on DE-MRI at 3 days. Furthermore, patchy
      microinfarct, as a result of microembolization, was visible as hyperenhanced zone
      at the borders of the contiguous infarct. The reduction in ejection fraction and
      increase in LV volumes on cine MRI were greater in group III than group II at 3
      days and 5 weeks, which may be attributed to the slow infarct resorption, MVO
      extents and patchy microinfarct at the borders. CONCLUSION: This MRI study
      illustrates the recently raised conjecture that MVO delays/inhibits infarct
      resorption (healing), accentuates LV hypertrophy and pathological remodeling.

PMID- 24449357
TI  - [Urological diseases in a "general practice" in the 17th and early 18th
      centuries].
AB  - Of national medicohistorical importance was the town physician Johannes Franc
      (1649-1725). His diary written in Latin gives - among other diseases - an
      overview of urological diseases affecting citizens in Ulm around 1700. It also
      allows a look into the "workshop" of a scholar who studied contemporary medicine
      in comprehensive manner. Franc's case reports illustrate a fundamental change in
      the perception of the patient at the end of the 17th/beginning of the 18th
      century.

PMID- 24449358
TI  - [Morbidity, mortality, and overall survival after radical cystectomy: comparison
      of single-center results with the literature and a nomogram].
AB  - BACKGROUND: Overall survival (OS) after radical cystectomy is determined. It is
      investigated retrospectively whether prediction is possible using a nomogram. A
      comparison with published data from "high-volume" centers is performed. PATIENTS
      AND METHODS: Data of 100 consecutive radical cystectomies performed between 2006
      and 2012 were collected. Age, ASA score, tumor stage, urinary diversion, and
      Clavien score were recorded. The OS after 2 and 5 years was recorded (Kaplan
      Meier analysis) and the nomogram-based predictive accuracy was calculated.
      RESULTS: Median age was 70.8 years. A T<=2, T3, T4, N+ stage was present in 40,
      37, 23, and 43%, respectively. Urinary diversion: neobladder, conduit, and
      ureterostomy were performed in 35, 53, and 12%. The 30-day mortality was 1%. At
      follow-up, there were 95 patients with a median observation time of 19.8 months.
      The 2- and 5-year OS were 0.68 and 0.45 (Kaplan-Meier analysis) and 0.65 and
      0.39, respectively (nomogram). A significant correlation was observed (rs=0.79;
      rs=0.80). Compared to published "high-volume" series, no relevant differences
      concerning morbidity, mortality, and OS were observed. However, there are
      significant differences concerning the characteristics of "high-volume centers".
      CONCLUSION: In this series, the OS can be predicted by a multivariate nomogram.
      The results are comparable with published data. There is no clear definition of a
      "high-volume center".

PMID- 24449359
TI  - Neonatal exposure to diethylstilbestrol causes granulomatous orchitis via
      epididymal inflammation.
AB  - Diethylstilbestrol (DES), an endocrine-disrupting chemical, is an infamous
      artificial estrogenic compound. Although neonatal exposure to DES has been shown
      to result in inflammation of the male reproductive system, it has not, to our
      knowledge, been reported to induce testicular inflammation. Here we report that
      neonatal exposure to DES caused granulomatous orchitis with spermatogenic
      disturbance in 4 of 17 ICR male mice at 12 weeks of age. In the animals with
      spermatogenic disturbance, we observed either seminiferous tubules containing
      only cells with Sertoli cell features (likely Sertoli cell syndrome), or tubule
      cells in maturation arrest that contained only spermatogonia and/or
      spermatocytes. Following neonatal DES exposure, 5-week-old mice exhibited
      inflammation in cauda epididymis; by 8 weeks, the inflammation had spread to all
      segments of epididymis but not the testis; by 12 weeks, inflammation of the
      epididymis was observed in all mice. These data indicated that cauda epididymis
      has increased sensitivity to neonatal DES exposure compared to other segments of
      epididymis and testis. The data also implied that neonatal DES exposure-induced
      inflammation in cauda epididymis extended gradually to the testis via corpus and
      caput during development. 

PMID- 24449360
TI  - Pig-a gene mutation and micronucleated reticulocyte induction in rats exposed to
      tumorigenic doses of the leukemogenic agents chlorambucil, thiotepa, melphalan,
      and 1,3-propane sultone.
AB  - To evaluate whether blood-based genotoxicity endpoints can provide temporal and
      dose-response data within the low-dose carcinogenic range that could contribute
      to carcinogenic mode of action (MoA) assessments, we evaluated the sensitivity of
      flow cytometry-based micronucleus and Pig-a gene mutation assays at and below
      tumorigenic dose rate 50 (TD50) levels. The incidence of micronucleated
      reticulocytes (MN-RET) was used to evaluate chromosomal damage, and the frequency
      of CD59-negative reticulocytes (RET(CD59-) ) and erythrocytes (RBC(CD59-) )
      served as phenotypic reporters of mutation at the X-linked Pig-a gene. Several
      leukemogenic agents with a presumed genotoxic MoA were studied. Specifically,
      male Sprague Dawley rats were treated via oral gavage for 28 days with
      chlorambucil, thiotepa, melphalan, and 1,3-propane sultone at doses corresponding
      to 0.33x, 1x, and 3x TD50, as well as at the maximum tolerated dose. Frequencies
      of MN-RET were determined at Days 4 and 29, and RET(CD59-) and RBC(CD59-) data
      were collected pretreatment as well as Days 15/16, 29, and 56/57. Dose-related
      increases were observed for each endpoint, and time to maximal effect was
      consistently: MN-RET < RET(CD59-)  < RBC(CD59-) . For each of the chemicals
      studied, the genotoxic events occurred long before tumors or preneoplastic
      lesions would be expected. Furthermore, in the case of Pig-a gene mutation, the
      responses were observed at or below the TD50 dose for three out of the four
      chemicals studied. These data illustrate the potential for quantitative blood
      based analyses to provide dose-response and temporality information that relates
      genetic damage to cancer induction.

PMID- 24449361
TI  - Individual identification of Chinese Holstein bull by 10 STR loci.
AB  - With the premium bull plays a growing important role in cattle industry, semen
      detection technology based on individual identification and phylogenetic
      relationship is paid more and more attention. In order to lay the foundation for
      the establishment of the China Holstein bull identification method, this research
      takes 20 Chinese Holstein dairy bull's blood and their corresponding semen, and
      then extracts the DNA both from the blood and semen, analysis the genetic
      polymorphisms of 10 microsatellite loci (TGLA227, INRA23, TGLA122, BM2113,
      SPS115, ETH3, ETH225, MCM158, MAF45 and UMN0108) by microsatellite marker,
      discuss the feasibility of this method used to individual identification. The
      results showed that Chinese Holstein dairy bull genetic diversity in the ten
      microsatellite loci were both high, and the average polymorphic information
      content of TGLA227, which highest, is 0.8162, ETH225 has the lowest, which is
      0.6224. Use STR loci to identify the bull's semen, the cumulative individual
      identification capacity is 99.99%, which indication that 10 STR loci can be used
      to the frozen semen quality test and cows individual identification.

PMID- 24449362
TI  - ABO blood group polymorphisms and risk for ischemic stroke and peripheral
      arterial disease.
AB  - Recent studies have demonstrated association between ABO blood system and
      thrombosis, indicating that individuals belonging to non-O blood groups (A, B or
      AB) present an increased risk of venous thrombosis, heart disease, and ischemic
      stroke (IS) as compared to O blood group carriers. In this study, we investigated
      the frequency of ABO blood group polymorphisms and its association with IS and
      peripheral arterial disease. Significant differences were observed for O1 (OR
      0.57, 95% CI 0.35-0.95, p < 0.05) and O2 (OR 3.47, 95% CI 1.15-10.28, p < 0.05)
      alleles among IS patients while significant differences were observed for B
      phenotype (26.3 vs 9.5%, OR 3.42, 95% CI 1.32-8.76, p = 0.01, patients vs
      controls, respectively) and alleles A1 (OR 0.31, 95% CI 0.11-0.84, p < 0.05), O2
      (OR 4.61, 95% CI 1.59-13.23, p < 0.01) and B (OR 3.42, 95% CI 1.62-7.13, p <
      0.001) alleles for PAD patients. O1 allele was an independent variable (OR 0.27,
      95% CI 0.12-0.57, p < 0.001) for IS patients. These data suggest the relationship
      of non-O blood groups in pathogenesis of thrombosis events and a possible
      protective effect of O blood group.

PMID- 24449363
TI  - Association of CYP1A1 and CYP2D6 gene polymorphisms with head and neck cancer in
      Tunisian patients.
AB  - The purpose of this study was to investigate the relationship between head and
      neck cancer (HNC) and environmental agents and polymorphisms in CYP1A1, CYP2D6,
      NAT1 and NAT2 metabolic enzymes genes. To the best of our knowledge, this is the
      first report on polymorphisms in CYP1A1 6310C>T, CYP2D6 Arg365His, NAT1 52936A>T
      and NAT2 Arg268Lys (NAT2*12A) genes and susceptibility to HNC in Tunisian
      population. We study the prevalence of these polymorphisms in 169 patients with
      HNC and 261 control subjects using polymerase chain reaction based methods in a
      Tunisian population. We detected an association between HNC and CYP1A1 6310C>T
      (TT) and CYP2D6 Arg365His (His/His) variant carriers (OR 1.75, P = 0.008 and OR
      1.66, P = 0.016, respectively). No association was found between the
      polymorphisms genotypes of NAT1 52936T>A and NAT2 Arg268Lys and risk of HNC. An
      association between HNC and CYP1A1 (TT) genotype was found among patients with
      smoking (P = 0.011) and drinking habit (P = 0.009). The combinations of NAT1 (AT
      or AA) and NAT2 (AA) at-risk genotypes increased HNC risk (OR 4.23, P = 0.005 and
      OR 3.60, P = 0.048, respectively). However, the combinations of CYP1A1 (AA) and
      CYP2D6 (CC) genotypes decreased risk of HNC (OR 0.20; P = 0.006). Genetic
      polymorphisms in CYP1A1 and CYP2D6 may significantly associate with HNC in the
      Tunisian population. The results of this study suggest a possible gene
      environment interaction for certain carcinogen metabolizing enzymes, but larger
      studies that fully evaluate the interaction are needed.

PMID- 24449364
TI  - MDR1 C3435T polymorphism and inflammatory bowel disease risk: a meta-analysis.
AB  - The C3435T polymorphism of the multidrug resistance gene (MDR1) has been
      implicated in inflammatory bowel disease (IBD) risk, but the reported results are
      inconsistent. Here we performed a meta-analysis to evaluate the association
      between C3435T polymorphism and the risk of IBD using all case-control studies
      published before February 2013 according to PubMed and Web of Science. A total of
      13 case-control studies, including 6,757 cases and 4,295 controls, were included.
      Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using
      fixed- or random-effects model. Overall, no evidence has indicated that the
      C3435T polymorphism was associated with the susceptibility to IBD (dominant
      model: OR = 1.05, 95 % CI: 0.96-1.16; CT vs. CC: OR = 1.06, 95 % CI: 0.95-1.17;
      TT vs. CC: OR = 1.04, 95 % CI: 0.92-1.17; recessive model: OR = 0.99, 95 % CI:
      0.90-1.09). Besides, stratified analysis by clinical type also indicated that no
      significant association between MDR1 C3435T and the risk of Crohn's disease and
      ulcerative colitis was observed. This meta-analysis indicated that the C3435T
      polymorphism of MDR1 may not confer susceptibility to IBD.

PMID- 24449365
TI  - Effect of dietary n-3 polyunsaturated fatty acids on transcription factor
      regulation in the bovine endometrium.
AB  - Dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation is postulated
      to have positive effects on fertility. The impact of dietary n-3 PUFA
      supplementation on physiological and biochemical processes involved in
      reproduction is likely to be associated with significant alterations in gene
      expression in key reproductive tissues which is in turn regulated by
      transcription factors. Beef heifers were supplemented with a rumen protected
      source of either a saturated fatty acid or high n-3 PUFA diet per animal per day
      for 45 days and uterine endometrial tissue was harvested post slaughter. A
      microarray analysis was conducted and bioinformatic tools were employed to
      evaluate the effect of n-3 PUFA supplementation on gene expression in the bovine
      endometrium. Clustering of microarray gene expression data was performed to
      identify co-expressed genes. Functional annotation of each cluster of genes was
      carried out using Ingenuity Pathway Analysis. Furthermore, oPOSSUM was employed
      to identify transcription factors involved in gene expression changes due to
      supplementary PUFA. Gene functions which showed a significant response to n-3
      PUFA supplementation included tissue development, immune function and
      reproductive function. Numerous transcription factors such as FOXD1, FOXD3,
      NFKB1, ESR1, PGR, FOXA2, NKX3-1 and PPARalpha were identified as potential
      regulators of gene expression in the endometrium of cattle supplemented with n-3
      PUFA. This study demonstrates the complex nature of the alterations in the
      transcriptional regulation process in the uterine endometrium of cattle following
      dietary supplementation which may positively influence the uterine environment. 

PMID- 24449366
TI  - Association of ADIPOQ gene with obesity and adiponectin levels in Malaysian
      Malays.
AB  - Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene
      have been linked with obesity and with adiponectin levels in various populations.
      Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261
      SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity
      parameters and adiponectin levels were measured in 574 subjects. Genotyping was
      performed using real-time polymerase chain reaction and Sequenom MassARRAY. A
      significant genotypic association was observed between ADIPOQ rs17366568 and
      obesity. The frequencies of AG and AA genotypes were significantly higher in the
      obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A
      alleles occurring among the obese group were twice those among the non-obese
      group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no
      significant association was found between allelic frequencies of ADIPOQ
      rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ
      rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not
      significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes
      of the ADIPOQ gene were not associated with obesity. We confirmed the previously
      reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs
      are not important modulators of adiponectin levels in this population.

PMID- 24449367
TI  - Molecular characterization and expression of type-I interferon gene in Labeo
      rohita.
AB  - Genes coding for type-I interferon (I-IFN) has been cloned from Labeo rohita, a
      commercially important and widely cultured fish in India and South East Asia. In
      the present study, full-length gene of I-IFN was amplified and sequenced. The
      sequence analysis revealed that I-IFN consists of 1,786 bp genomic sequence with
      four introns and five exons and an ORF of 546 bp encoding for a putative protein
      of 181 amino acids. The mature protein has a molecular weight of 18.97 kDa and
      consists of 158 amino acids and a signal peptide of 23 amino acids at the N
      terminus. The sequence carries I-IFN signature motif, one glycosylation site, two
      conserved cystine amino acids and other conserved amino acids. The sequence
      showed highest similarity to that of Cyprinus carpio (84%). In silico analysis of
      the rohu I-IFN protein was done using various bioinformatic tools. The
      constitutive expression of I-IFN gene was found to be more in spleen compared to
      gill and kidney in real time PCR assay. Expression of I-IFN increased about 20
      fold in cultured kidney cell 2 h after induction with poly I:C and showed maximum
      expression at 8 h post-induction.

PMID- 24449368
TI  - Increased risk of colorectal malignant neoplasm in patients with nonalcoholic
      fatty liver disease: a large study.
AB  - Nonalcoholic fatty liver disease (NAFLD) has been suggested to be a strong risk
      factor of colorectal benign adenomas and advanced neoplasms. The aim of this
      large cohort study was to further investigate the prevalence of colorectal
      malignant neoplasm (CRMN) in patients with NAFLD and determine whether
      association between NAFLD and CRMN exists. 2,315 community subjects (1,370 males
      and 945 females) who underwent a routine colonoscopy according to international
      colorectal cancer screening guideline were recruited. Nature of colorectal
      lesions determined by biopsy and NAFLD was diagnosed by ultrasound. Binary
      logistic regression analysis was applied to explore the related associations.
      Prevalence of CRMN was 29.3% (77/263) in patients with NAFLD, which was
      significantly higher than 18.0% (369/2,052) in the control group (P<0.05). In
      addition, malignant neoplasm in NAFLD group occurred more frequently at sigmoid
      colon than in control group (14.3 vs. 11.9%). The incidence of highly
      differentiated colorectal adenocarcinoma in NAFLD group was significantly higher
      than control group (62.3 vs. 9.8%). Univariate analysis showed that NAFLD had
      strong association with CRMN (OR 2.043; 95% CI 1.512-2.761; P<0.05). After
      adjusting for metabolic and other confounding factors, NAFLD remained as an
      independent risk factor for CRMN (OR 1.868; 95% CI 1.360-2.567; P<0.05). NAFLD
      was an independent risk factor for CRMN. Sigmoid carcinoma and highly
      differentiated colorectal adenocarcinoma were more commonly found in NAFLD.
      (ClinicalTrials.gov number, NCT01657773, website:
      http://clinicaltrials.gov/ct2/show/NCT01657773?term=zheng+minghua&rank=1 ).

PMID- 24449369
TI  - SLC30A8 gene polymorphism (rs13266634 C/T) and type 2 diabetes mellitus in south
      Iranian population.
AB  - Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder which is
      characterized by chronic hyperglycemia. T2DM is due to the interplay of genetic
      susceptibility and environmental factors. Zinc is an important element for
      insulin storage and secretion. Zinc transporters ensure zinc transportation
      across the biological membranes and enable the cellular flow of zinc into the
      extracellular matrix or the intracellular vesicles. Solute carrier family 30
      member 8 (SLC30A8) gene encodes zinc transporter protein member 8. The rs13266634
      C/T polymorphism in SLC30A8 gene has been reported with higher risk of T2DM in
      literature. Thus, the present study aimed to investigate the association between
      rs13266634 polymorphism and T2DM in Fars province, Southern Iran and compare the
      results with other populations. A total of 306 subjects were collected from the
      outpatients of Shahid Motahhari clinic affiliated to Shiraz University of Medical
      Sciences, Shiraz, Iran. These subjects were genotyped using polymerase chain
      reaction-restriction fragment length polymorphism and validated by direct
      sequencing. The frequency of CC genotype in diabetic and control groups was 90
      (59.6%) and 89 (57.4%). The number of CT genotype was 51 (33.8%) in the case and
      49 (31.6%) in the control group. The TT genotype was 10 (6.6%) and 17 (11%) in
      diabetic and non-diabetic subjects, respectively. No significant difference was
      found between the normal and T2DM subjects regarding the allelic and genotypic
      distribution (p=0.35, OR=1.19, 95% CI 0.82-1.7) and (p=0.94, OR=1.7, 95% CI 0.7
      3.9). No significant difference was found between the normal and diabetic
      subjects regarding the rs13266634 C/T polymorphism in SLC30A8 gene. In comparison
      with other ethnic groups, the C allele frequency in our population was very
      similar to that of the European but higher than that of the Eastern Asian and
      lower than the African populations.

PMID- 24449370
TI  - Adaptive developmental plasticity in methylene tetrahydrofolate reductase (MTHFR)
      C677T polymorphism limits its frequency in South Indians.
AB  - Methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism shows
      considerable heterogeneity in its distribution in humans worldwide. The current
      study was conducted to investigate whether this polymorphism exhibited adaptive
      developmental plasticity in the control of the TT-genotype frequency. We screened
      1,818 South Indian subjects (895 males and 923 females) for MTHFR C677T
      polymorphism using PCR-restriction fragment length polymorphism approach. MTHFR
      677T-allele frequency in males and females was 9.1 and 11.0%, respectively.
      Compared to females, males had lower frequency of TT-genotype [odds ratio 0.31,
      95% confidence interval (CI) 0.08-1.01]. The frequency of MTHFR 677T-allele was
      highest in the age group of 20-40 years and it gradually decreased from 40-60 to
      60-80 years (P trend<0.0001). MTHFR 677TT-genotype was associated with 7.02-folds
      (95% CI: 2.12-25.63, P<0.0001) cumulative risk for recurrent pregnancy loss
      (RPL), neural tube defects (NTDs) and deep vein thrombosis (DVT). Linear
      regression model suggested that male gender exhibited increased homocysteine
      levels by 9.35 MUmol/L while each MTHFR 677T-allele contributed to 4.63 MUmol/L
      increase in homocysteine. Plasma homocysteine showed inverse correlation with
      dietary folate (r=-0.17, P<0.0001), B2 (r=-0.14, P<0.0001) and B6 (r=-0.07,
      P=0.03). Examination of the spontaneously aborted fetuses (n=35) showed no
      significant association of fetal genotype on its in utero viability. From the
      current study, it was concluded that C677T seemed to have acquired adaptive
      developmental plasticity among South Indians due to environmental influences thus
      contributing to hyperhomocysteinemia and its associated complications such as
      RPL, NTDs, DVT, etc.

PMID- 24449371
TI  - Accumulation of lipofuscin-like pigments of walnuts (Carya cathayensis) during
      storage: potential roles of lipid oxidation and non-enzymatic glycosylation.
AB  - BACKGROUND: Lipofuscin-like pigments (LFLP) are considered a hallmark of aging.
      The intracellular LFLP formation rate is negatively correlated with the life
      expectancy of cell. In food quality, increase of LFLP not only affects the
      appearance but also causes loss of nutritional value. RESULTS: The accumulation
      of LFLP increased during storage of all walnuts. LFLP fluorescent intensities of
      walnuts with 4%, 6%, 12% and 16% moisture at the end of storage were 8.1, 4.8,
      4.3 and 2.8 times those at the beginning, respectively. The LFLP accumulation of
      walnuts with high moisture was found to be negatively correlated with soluble
      sugars and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching rate, but
      positively correlated with the content of hydroxymethylfuraldehyde (HMF). While
      the LFLP accumulation of walnuts with low moisture had a strong positive
      correlation with anisidine value, it exhibited high negative correlations with
      acid phosphatase activity, DPPH(*) quenching rate and tocopherol content.
      CONCLUSION: In walnuts with low initial moisture, lipoxidation products increased
      markedly during storage and these products might provide the source for LFLP
      accumulation. On the other hand, in walnuts with high initial moisture, reducing
      sugars derived from the hydrolysis of soluble sugars might play an important role
      in initiating the Maillard-like reaction, leading to LFLP accumulation.

PMID- 24449372
TI  - Changing patterns of mobility as a response to climatic deterioration and
      aridification in the middle Holocene Southern Sahara.
AB  - The African Humid Period witnessed a rapid human re-occupation of the Sahara as
      numerous lakes formed during the Holocene climatic optimum circa 10-5 kya.
      Permanent waters attracted a variety of aquatic and terrestrial fauna allowing
      for long-term occupation of specific paleolake basins. The Gobero paleolake in
      central Niger was one such location that preserves a unique mortuary record from
      the southern Sahara. Here, we use radiogenic strontium isotope analysis to
      investigate how human communities adapted to aridification throughout the
      Holocene. In particular, we examine the effects of increasing climate instability
      on patterns of human mobility. Results of radiogenic strontium isotope analysis
      of enamel and bone samples from Middle Holocene burials (~7.2-4.9 kya) indicate
      predominantly local values with no evidence for sex-based variation. Comparisons
      of radiogenic strontium isotope data with previously published (Stojanowski and
      Knudson: Am J Phys Anthropol 146 (2011) 49-61) Early Holocene burials (~9.7-8.3
      kya) indicate significant differences in both enamel and bone values. Middle
      Holocene individuals demonstrate a predominantly non-local signature for enamel
      values and a predominantly local signature for bone values. Those individuals
      with non-local bone values always demonstrated non-local enamel values; however,
      the opposite was not the case. This suggests a divergence of mobility strategies
      during the Middle Holocene with a minority of individuals maintaining a more
      mobile existence throughout their life and others maintaining a similar strategy
      as Early Holocene hunter-gatherers that was tied to the paleolake basin. The more
      mobile individuals likely lived during the terminal phase of the lake's
      occupation. One response to aridification by Saharan peoples, then, was
      increasing mobility.

PMID- 24449373
TI  - In vitro studies on the relationship between the antioxidant activities of some
      berry extracts and their binding properties to serum albumin.
AB  - The aim of this study was to investigate the possibility to use the bioactive
      components from cape gooseberry (Physalis peruviana), blueberry (Vaccinium
      corymbosum), and cranberry (Vaccinium macrocarpon) extracts as a novel source
      against oxidation in food supplementation. The quantitative analysis of bioactive
      compounds (polyphenols, flavonoids, flavanols, carotenoids, and chlorophyll) was
      based on radical scavenging spectrophometric assays and mass spectrometry. The
      total phenolic content was the highest (P < 0.05) in water extract of blueberries
      (46.6 +/- 4.2 mg GAE/g DW). The highest antioxidant activities by 2,2-diphenyl-1
      picrylhydrazyl radical scavenging assay and Cupric reducing antioxidant capacity
      were in water extracts of blueberries, showing 108.1 +/- 7.2 and 131.1 +/- 9.6
      MUMTE/g DW with correlation coefficients of 0.9918 and 0.9925, and by beta
      carotene linoleate assay at 80.1 +/- 6.6 % with correlation coefficient of
      0.9909, respectively. The water extracts of berries exhibited high binding
      properties with human serum albumin in comparison with quercetin. In conclusion,
      the bioactive compounds from a relatively new source of gooseberries in
      comparison with blueberries and cranberries have the potential as food
      supplementation for human health. The antioxidant and binding activities of
      berries depend on their bioactive compounds.

PMID- 24449374
TI  - Antibacterial activity of Kaempferia rotunda rhizome lectin and its induction of
      apoptosis in Ehrlich ascites carcinoma cells.
AB  - The tuberous rhizome Kaempferia rotunda Linn. has been used as food and
      traditional medicinal plant, and the purified K. rotunda lectin (KRL) showed
      antiproliferative activity against Ehrlich ascites carcinoma cells [1]. In the
      present study, KRL showed agglutination activity against Escherichia coli and
      Staphylococcus aureus, with partial inhibition of their growth. MTT assay was
      used to investigate the effect of KRL on EAC cells in vitro in RPMI-1640 medium,
      and it was found that lectin inhibited 6.2-50.5% cell growth at the range of 7.5
      120 MUg/ml protein concentration. The cell cycle arrest at G0/G1 phase of EAC
      cells was also determined by flow cytometry after treatment with lectin. The
      apoptotic cell morphological changes of the treated EAC cells were confirmed by
      fluorescence and optical microscope. In the presence of caspase-3 inhibitor, the
      cell growth inhibition of the lectin was reduced significantly. RT-PCR was used
      to evaluate the expression of apoptosis-related genes, bcl-2, bcl-X, and bax. Bax
      gene expression was intensively increased with the despaired of bcl-X gene
      expression and significant decrease of bcl-2 gene expression in the cells treated
      with KRL. Thus, lectin induced apoptotic cell death in Ehrlich ascites carcinoma
      cells.

PMID- 24449375
TI  - Fractionation of protein hydrolysates of fish and chicken using membrane
      ultrafiltration: investigation of antioxidant activity.
AB  - In this work, chicken and fish peptides were obtained using the proteolytic
      enzymes alpha-Chymotrypsin and Flavourzyme. The muscle was hydrolyzed for 4 h,
      and the resulting peptides were evaluated. Hydrolysates were produced from
      Argentine croaker (Umbrina canosai) with a degree of hydrolysis (DH) of 25.9 and
      27.6% and from chicken (Gallus domesticus) with DH of 17.8 and 20.6% for
      Flavourzyme and alpha-Chymotrypsin, respectively. Membrane ultrafiltration was
      used to separate fish and chicken hydrolysates from Flavourzyme and alpha
      Chymotrypsin based on molecular weight cutoff of >1,000, <1,000 and >500, and
      <500 Da, to produce fractions (F1,000, F1,000-500, and F500) with antioxidant
      activity. Fish hydrolysates produced with Flavourzyme (FHF) and alpha
      Chymotrypsin showed 60.8 and 50.9% of peptides with a molecular weight of <3 kDa
      in its composition, respectively. To chicken hydrolysates produced with
      Flavourzyme and alpha-Chymotrypsin (CHC) was observed 83 and 92.4% of peptides
      with a molecular weight of <3 kDa. The fraction that showed, in general, higher
      antioxidant potential was F1,000 from FHF. When added 40 mg/mL of FHF and CHC, 93
      and 80% of lipid oxidation in ground beef homogenates was inhibited,
      respectively. The composition of amino acids indicated higher amino acids
      hydrophobic content and amino acids containing sulfuric residues for FHF, which
      showed antioxidant potential.

PMID- 24449376
TI  - Effect of salts (NaCl and Na2CO3) on callus and suspension culture of Stevia
      rebaudiana for Steviol glycoside production.
AB  - Steviol glycosides are natural non-caloric sweeteners which are extracted from
      the leaves of Stevia rebaudiana plant. Present study deals the effect of salts
      (NaCl and Na2CO3) on callus and suspension culture of Stevia plant for steviol
      glycoside (SGs) production. Yellow-green and compact calli obtained from in vitro
      raised Stevia leaves sub-cultured on MS medium supplemented with 2.0 mg l(-1) NAA
      and different concentrations of NaCl (0.05-0.20%) and Na2CO3 (0.0125-0.10%) for 2
      weeks, and incubated at 24 +/- 1  degrees C and 22.4 MUmol m(-2) s(-1) light
      intensity provided by white fluorescent tubes for 16 h. Callus and suspension
      biomass cultured on salts showed less growth as well as browning of medium when
      compared with control. Quantification of SGs content in callus culture (collected
      on 15th day) and suspension cultures (collected at 10th and 15th days) treated
      with and without salts were analyzed by HPLC. It was found that abiotic stress
      induced by the salts increased the concentration of SGs significantly. In callus,
      the quantity of SGs got increased from 0.27 (control) to 1.43 and 1.57% with
      0.10% NaCl, and 0.025% Na2CO3, respectively. However, in case of suspension
      culture, the same concentrations of NaCl and Na2CO3 enhanced the SGs content from
      1.36 (control) to 2.61 and 5.14%, respectively, on the 10th day.

PMID- 24449377
TI  - An atmospheric-pressure plasma-treated titanium surface potentially supports
      initial cell adhesion, growth, and differentiation of cultured human prenatal
      derived osteoblastic cells.
AB  - An atmospheric-pressure plasma (APP) treatment was recently reported to render
      titanium (Ti) surfaces more suitable for osteoblastic cell proliferation and
      osteogenesis. However, the mechanism of action remains to be clearly
      demonstrated. In this study, we focused on cell adhesion and examined the effects
      of the APP treatment on the initial responses of human prenatal-derived
      osteoblastic cells incubated on chemically polished commercially pure Ti (CP
      cpTi) plates. In the medium containing 1% fetal bovine serum, the initial cell
      adhesion and the actin polymerization were evaluated by scanning electron
      microscopy and fluorescence microscopy. The expression of cell adhesion-related
      molecules and osteoblast markers at the messenger RNA level was assessed by real
      time quantitative polymerase chain reaction. Although the cells on the APP
      treated CP-cpTi surface developed fewer cytoskeletal actin fibers, they attached
      with higher affinity and consequently proliferated more actively (1.46-fold over
      control at 72 h). However, most of the cell adhesion molecule genes were
      significantly downregulated (from 40 to 85% of control) in the cells incubated on
      the APP-treated CP-cpTi surface at 24 h. Similarly, the osteoblast marker genes
      were significantly downregulated (from 49 to 63% of control) at 72 h. However,
      the osteoblast marker genes were drastically upregulated (from 197 to 296% of
      control) in these cells by dexamethasone and beta-glycerophosphate treatment.
      These findings suggest that the APP treatment improves the ability of the CP-cpTi
      surface to support osteoblastic proliferation by enhancing the initial cell
      adhesion and supports osteoblastic differentiation when immature osteoblasts
      begin the differentiation process.

PMID- 24449378
TI  - Might audit of digital equipment shed light on NHS bed crisis?

PMID- 24449379
TI  - Doppler assessment of splanchnic arterial flow in patients with liver cirrhosis:
      correlation with ammonia plasma levels and MELD score.
AB  - PURPOSE: To assess the clinical significance of blood flow velocity and
      resistance index (RI) in the visceral arteries of patients with liver cirrhosis
      with respect to plasma ammonia (NH3) level and liver function. METHODS: We
      included 80 patients with liver cirrhosis (58 men) and 20 healthy controls (11
      men). Duplex Doppler ultrasonography was used to assess flow velocity and RI in
      the hepatic (HA), right (RRA), and left renal (LRA), and splenic (SA) (LA)
      artery. Plasma NH3 was measured by biochemistry. Liver function was assessed by
      MELD score (model of end-stage liver disease). RESULTS: HA, LRA, and SA systolic
      flow velocities were greater, whereas RRA diastolic velocity was lower in
      patients with liver cirrhosis than in controls RI was higher in LRA, RRA, SA, and
      HA in patients with liver cirrhosis than in controls. NH3 levels were
      significantly elevated in all patients with liver cirrhosis (p < 0.05) and
      significantly correlated with RI of RRA, LRA, and SA. CONCLUSION: We found
      greater renal, hepatic, and LA RI in patients with liver cirrhosis than in
      healthy controls. The correlation we found between elevated renal artery RI
      (>=0.70) and MELD score emphasizes the risk of renal dysfunction during
      progression of liver cirrhosis.

PMID- 24449380
TI  - Self-assembly of pi-conjugated gelators into emissive chiral nanotubes: emission
      enhancement and chiral detection.
AB  - A series of new pi-conjugated gelators that contain various aromatic rings
      (phenyl, naphthyl, 9-anthryl) and amphiphilic L-glutamide was designed, and their
      gel formation in organic solvents and self-assembled nanostructures was
      investigated. The gelators showed good gelation ability in various organic
      solvents that ranged from polar to nonpolar. Those gelator molecules with small
      rings such as phenyl and naphthyl self-assembled into nanotube structures in most
      organic solvents and showed strong blue emission. However, the 9-anthryl
      derivative formed only a nanofiber structure in any organic solvent, probably
      owing to the larger steric hindrance. All of these gels showed enhanced
      fluorescence in organogels. Furthermore, during the gel formation, the chirality
      at the L-glutamide moiety was transferred to the nanostructures, thus leading to
      the formation of chiral nanotubes. One of the nanotubes showed chiral recognition
      toward the chiral amines. 

PMID- 24449381
TI  - Ordered hybrids from template-free organosilane self-assembly.
AB  - Despite considerable achievements over the last two decades, nonporous organic
      inorganic hybrid materials are mostly amorphous, especially in the absence of
      solvothermal processes. The organosilane self-assembly approach is one of the few
      opportunities for creating a regular assembly of organic and inorganic moieties.
      Additionally, well-established organosilicon chemistry enables the introduction
      of numerous organic functionalities. The synthesis of periodically ordered
      hybrids relies on mono-, bis-, or multisilylated organosilane building blocks
      self-assembling into hybrid mesostructures or superstructures, subsequently cross
      linked by siloxane Si-O-Si condensation. The general synthesis procedure is
      template-free and one-step. However, three concurrent processes underlie the
      generation of self-organized hybrid networks: thermodynamics of amphiphilic
      aggregation, dynamic self-assembly, and kinetically controlled sol-gel chemistry.
      Hence, the set of experimental conditions and the precursor structure are of
      paramount importance in achieving long-range order. Since the first developments
      in the mid-1990s, the subject has seen considerable progress leading to many
      innovative advanced nanomaterials providing promising applications in membranes,
      pollutant remediation, catalysis, conductive coatings, and optoelectronics. This
      work reviews, comprehensively, the primary evolution of this expanding field of
      research. 

PMID- 24449382
TI  - The capability to synthesize phytochelatins and the presence of constitutive and
      functional phytochelatin synthases are ancestral (plesiomorphic) characters for
      basal land plants.
AB  - Bryophytes, a paraphyletic group which includes liverworts, mosses, and
      hornworts, have been stated as land plants that under metal stress (particularly
      cadmium) do not synthesize metal-binding peptides such as phytochelatins.
      Moreover, very little information is available to date regarding phytochelatin
      synthesis in charophytes, postulated to be the direct ancestors of land plants,
      or in lycophytes, namely very basal tracheophytes. In this study, it was
      hypothesized that basal land plants and charophytes have the capability to
      produce phytochelatins and possess constitutive and functional phytochelatin
      synthases. To verify this hypothesis, twelve bryophyte species (six liverworts,
      four mosses, and two hornworts), three charophytes, and two lycophyte species
      were exposed to 0-36 MUM cadmium for 72 h, and then assayed for: (i) glutathione
      and phytochelatin quali-quantitative content by HPLC and mass spectrometry; (ii)
      the presence of putative phytochelatin synthases by western blotting; and (iii)
      in vitro activity of phytochelatin synthases. Of all the species tested, ten
      produced phytochelatins in vivo, while the other seven did not. The presence of a
      constitutively expressed and functional phytochelatin synthase was demonstrated
      in all the bryophyte lineages and in the lycophyte Selaginella denticulata, but
      not in the charophytes. Hence, current knowledge according to phytochelatins have
      been stated as being absent in bryophytes was therefore confuted by this work. It
      is argued that the capability to synthesize phytochelatins, as well as the
      presence of active phytochelatin synthases, are ancestral (plesiomorphic)
      characters for basal land plants.

PMID- 24449383
TI  - APUM23, a PUF family protein, functions in leaf development and organ polarity in
      Arabidopsis.
AB  - The normal biological function of leaves, such as intercepting light and
      exchanging gases, relies on proper differentiation of adaxial and abaxial
      polarity. KANADI (KAN) genes, members of the GARP family, are key regulators of
      abaxial identity in leaf morphogenesis. This study identified a mutant allele
      (apum23-3) of APUM23, which encodes a Pumilio/PUF domain protein and acts as an
      enhancer of the kan mutant. Arabidopsis APUM23 has been shown to function in pre
      rRNA processing and play pleiotropic roles in plant development. The apum23-3
      mutant also synergistically interacts with other leaf polarity mutants, affects
      proliferation of division-competent cells, and alters the expression of important
      leaf polarity genes. These phenotypes show that APUM23 has critical functions in
      plant development, particularly in polarity formation. The PUF gene family is
      conserved across kingdoms yet it has not been well characterized in plants. These
      results illuminating the functions of APUM23 suggest a novel role for PUF genes
      in Arabidopsis leaf development.

PMID- 24449384
TI  - The chloride channel family gene CLCd negatively regulates pathogen-associated
      molecular pattern (PAMP)-triggered immunity in Arabidopsis.
AB  - Chloride channel (CLC) family genes are ubiquitous from prokaryotes to eukaryotes
      and encode proteins with both channel and transporter activities. The Arabidopsis
      thaliana genome encodes seven CLC genes, and their products are found in a
      variety of cellular compartments and have various physiological functions.
      However, a role for AtCLCs in plant innate immunity has not previously been
      demonstrated. Here it is reported that AtCLCd is a negative regulator of pathogen
      associated molecular pattern (PAMP)-triggered immunity (PTI). T-DNA insertion
      mutants of AtCLCd exhibited enhanced responses to the elicitor, flg22. The PTI
      phenotypes of the clcd mutants were rescued by expression of AtCLCd.
      Overexpression of AtCLCd led to impaired flg22-induced responses. In line with a
      role for AtCLCd in PTI, the clcd mutants were more resistant to a virulent strain
      of the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 when spray
      inoculated, while AtCLCd-overexpressing lines displayed increased susceptibility
      to this pathogen. Interestingly, flg22 treatment was found to repress the
      expression of AtCLCd. In addition, its expression was elevated in mutants of the
      flg22 pattern recognition receptor (PRR) FLS2 and the PRR regulatory proteins
      BAK1 and BKK1, and reduced in an FLS2-overexpressing line. These latter findings
      indicate that FLS2 complexes regulate the expression of AtCLCd, further
      supporting a role for AtCLCd in PTI. 

PMID- 24449385
TI  - Taking one for the team: self-recognition and cell suicide in pollen.
AB  - Self-incompatibility (SI) is an important genetically controlled mechanism used
      by many angiosperms to prevent self-fertilization and inbreeding. A multiallelic
      S-locus allows discrimination between 'self' (incompatible) pollen from 'nonself'
      pollen at the pistil. Interaction of matching pollen and pistil S-determinants
      allows 'self' recognition and triggers rejection of incompatible pollen. The S
      determinants for Papaver rhoeas (poppy) are PrsS and PrpS. PrsS is a small
      secreted protein that acts as a signalling ligand to interact with its cognate
      pollen S-determinant PrpS, a small novel transmembrane protein. Interaction of
      PrsS with incompatible pollen stimulates increases in cytosolic free Ca(2+) and
      involves influx of Ca(2+) and K(+). Data implicate involvement of reactive oxygen
      species and nitric oxide signalling in the SI response. Downstream targets
      include the cytoskeleton, a soluble inorganic pyrophosphatase, Pr-p26.1, and a
      MAP kinase, PrMPK9-1. A major focus for SI-induced signalling is to initiate
      programmed cell death (PCD). In this review we provide an overview of our
      understanding of SI, with focus on how the signals and components are integrated,
      in particular, how reactive oxygen species, nitric oxide, and the actin
      cytoskeleton feed into a PCD network. We also discuss our recent functional
      expression of PrpS in Arabidopsis thaliana pollen in the context of understanding
      how PCD signalling systems may have evolved. 

PMID- 24449386
TI  - A maize root tip system to study DNA replication programmes in somatic and
      endocycling nuclei during plant development.
AB  - The progress of nuclear DNA replication is complex in both time and space, and
      may reflect several levels of chromatin structure and 3-dimensional organization
      within the nucleus. To understand the relationship between DNA replication and
      developmental programmes, it is important to examine replication and nuclear
      substructure in different developmental contexts including natural cell-cycle
      progressions in situ. Plant meristems offer an ideal opportunity to analyse such
      processes in the context of normal growth of an organism. Our current
      understanding of large-scale chromosomal DNA replication has been limited by the
      lack of appropriate tools to visualize DNA replication with high resolution at
      defined points within S phase. In this perspective, we discuss a promising new
      system that can be used to visualize DNA replication in isolated maize (Zea mays
      L.) root tip nuclei after in planta pulse labelling with the thymidine analogue,
      5-ethynyl-2'-deoxyuridine (EdU). Mixed populations of EdU-labelled nuclei are
      then separated by flow cytometry into sequential stages of S phase and examined
      directly using 3-dimensional deconvolution microscopy to characterize spatial
      patterns of plant DNA replication. Combining spatiotemporal analyses with studies
      of replication and epigenetic inheritance at the molecular level enables an
      integrated experimental approach to problems of mitotic inheritance and cellular
      differentiation. 

PMID- 24449387
TI  - Rubisco expression in the dinoflagellate Symbiodinium sp. is influenced by both
      photoperiod and endosymbiotic lifestyle.
AB  - Although the importance of anthozoan-dinoflagellate (genus Symbiodinium)
      endosymbioses in the establishment of coral reef ecosystems is evident, little is
      known about the molecular regulation of photosynthesis in the intra-gastrodermal
      symbiont communities, particularly with respect to the rate-limiting Calvin cycle
      enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco). In this study,
      we analyzed rubisco mRNA (rbcL) and protein (RBCL) concentrations over the diel
      cycle in both cultured and endosymbiotic Symbiodinium samples. In the former,
      rbcL expression increased upon illumination and decreased during the dark, a
      pattern that was upheld under continual dark incubation. A different trend in
      rbcL expression was observed in endosymbiotic Symbiodinium residing within sea
      anemone (Aiptasia pulchella) tissues, in which illumination gradually led to
      decreased rbcL mRNA expression. Unexpectedly, RBCL protein expression did not
      vary over time within anemone tissues, and in neither cultured nor endosymbiotic
      samples was a correlation between gene and protein expression documented. It
      appears, then, that photoperiod, lifestyle, and posttranscriptional regulation
      are all important drivers of RBCL expression in this ecologically important
      dinoflagellate. 

PMID- 24449388
TI  - 2,5-Diketopiperazines produced by Bacillus pumilus during bacteriolysis of
      Arthrobacter citreus.
AB  - We report the detection by gas chromatography/mass spectrometry and liquid
      chromatography/mass spectrometry analyses of the secreted 2,5-diketopiperazines
      (DKPs) cyclo(-Ala-Pro), cyclo(-Gly-Pro), cyclo(-Val-Pro), cyclo(-Ile-Pro), cyclo(
      Leu-Pro), cyclo(-Pro-Pro), cyclo(-HyP-Pro), cyclo(-Met-Pro), and cyclo(-Phe-Pro)
      produced by Bacillus pumilus. The study focuses on a marine isolate and a
      laboratory test strain of B. pumilus with capabilities to lyse pregrown living
      cell lawns of different bacterial species, among them Arthrobacter citreus.
      Chromatographic methods were used to analyze induced bioactive compounds. At
      least 13 different DKPs are produced by B. pumilus. Both strains respond with an
      increased production of the DKPs cyclo(-Gly-Pro), cyclo(-Ala-Pro), and cyclo(-Val
      Pro) to the presence of pasteurized A. citreus cells after 4 h in a nutrient-poor
      liquid medium. In agar diffusion assays, these DKPs did not cause lysis zones in
      living cell lawns, but they did inhibit further growth of several pregrown test
      bacteria in microplates even at concentrations as low as 1 MUg ml(-1). Antibiotic
      substances produced by B. pumilus after 20 h of cultivation in a special lysis
      medium showed lytic activity in cell-free extracts of B. pumilus culture
      supernatants.

PMID- 24449389
TI  - Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the
      cluster effect on the killing of tumor cells.
AB  - Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor
      associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys
      lipopeptide through click reactions. These vaccines elicited immune responses in
      mice without the use of any external adjuvant. The vaccine containing four copies
      of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in
      mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and
      initiate the killing of these tumor cells by activation of the complement
      dependent cytotoxicity complex. 

PMID- 24449390
TI  - Sulfo-NHS-SS-biotin derivatization: a versatile tool for MALDI mass analysis of
      PTMs in lysine-rich proteins.
AB  - The discovery of PTMs in proteins by MS requires nearly complete sequence
      coverage of the detected proteolytic peptides. Unfortunately, mass spectrometric
      analysis of the desired sequence fragments is often impeded due to low ionization
      efficiency and/or signal suppression in complex samples. When several lysine
      residues are in close proximity tryptic peptides may be too short for mass
      analysis. Moreover, modified peptides often appear in low stoichiometry and need
      to be enriched before analysis. We present here how the use of sulfo-NHS-SS
      biotin derivatization of lysine side chain can help to detect PTMs in lysine-rich
      proteins. This label leads to a mass shift which can be adjusted by reduction of
      the SS bridge and alkylation with different reagents. Low intensity peptides can
      be enriched by use of streptavidin beads. Using this method, the functionally
      relevant protein kinase A phosphorylation site in 5-lipoxygenase was detected for
      the first time by MS. Additionally, methylation and acetylation could be
      unambiguously determined in histones. 

PMID- 24449391
TI  - Concise review: Defining and targeting myeloma stem cell-like cells.
AB  - Multiple myeloma (MM) remains incurable despite recent advances in the treatment
      of MM. Although the idea of MM cancer stem cells (CSCs) has been proposed for the
      drug resistance in MM, MM CSCs have not been properly defined yet. Besides
      clonotypic B cells, phenotypically distinct MM plasma cell fractions have been
      demonstrated to possess a clonogenic capacity, leading to long-lasting
      controversies regarding the cells of origin in MM or MM-initiating cells.
      However, MM CSCs may not be a static population and survive as phenotypically and
      functionally different cell types via the transition between stem-like and non
      stem-like states in local microenvironments, as observed in other types of
      cancers. Targeting MM CSCs is clinically relevant, and different approaches have
      been suggested to target molecular, metabolic and epigenetic signatures, and the
      self-renewal signaling characteristic of MM CSC-like cells.

PMID- 24449394
TI  - Improving ryegrass-clover pasture dry matter yield and urea efficiency with
      gibberellic acid.
AB  - BACKGROUND: The effects of spraying gibberellic acid (GA3) at 20 or 30 g ha(-1),
      with or without application of urea, on pasture dry matter (DM) yield, herbage
      nitrogen (N) concentration and feed quality were investigated in 2011 and 2012
      for managed pastoral systems in New Zealand across a range of sites, in both
      autumn and spring. RESULTS: On the Waikato site (autumn and spring, 2012), and at
      all five sites in 2011, liquid urea applied with GA3 at 20 or 30 g ha(-1)
      consistently produced significantly higher pasture shoot DM yield, relative to
      liquid urea alone. Application of GA3 alone reduced feed quality by lowering
      metabolizable energy, crude protein and organic matter digestibility values.
      However, a reduced feed quality was not observed when GA3 was applied together
      with liquid urea. Liquid urea applied with GA3 also reduced total N and nitrate-N
      concentration in herbage, relative to liquid urea applied alone. CONCLUSION:
      Application of GA3 together with liquid urea provides an opportunity for the
      strategic use of urea to meet both production and environmental goals.

PMID- 24449393
TI  - Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes
      without known heart disease: the Thousand & 1 Study.
AB  - AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type
      1 diabetes. Early identification is vitally important. We sought to determine the
      prevalence and clinical characteristics associated with subclinical impaired
      systolic and diastolic function in type 1 diabetes patients without known heart
      disease. METHODS: In this cross-sectional examination of 1,093 type 1 diabetes
      patients without known heart disease, randomly selected from the Steno Diabetes
      Center, complete clinical and echocardiographic examinations were performed and
      analysed in uni- and multivariable regression models. RESULTS: The mean (SD) age
      was 49.6 (15) years, 53% of participants were men, and the mean duration of
      diabetes was 25.5 (15) years. Overall, 15.5% (n = 169) of participants had
      grossly abnormal systolic or diastolic function, including 1.7% with left
      ventricular ejection fraction (LVEF) < 45% and 14.4% with evidence of long
      standing diastolic dysfunction. In univariable models, clinical characteristics
      associated with abnormal myocardial function were: age (per 10 years), OR (95%
      CI) 2.1 (1.8, 2.4); diabetes duration (per 10 years), 1.7 (1.4, 1.9); systolic BP
      >= 140 mmHg, 2.7 (1.9, 3.8); diastolic BP >= 90 mmHg, 1.8 (1.0, 3.1); estimated
      (e)GFR < 60 ml min(-1) 1.73 m(-2), 3.8 (2.5, 5.9); microalbuminuria, 2.0 (1.3,
      3.0); macroalbuminuria, 5.9 (3.8, 9.3); proliferative retinopathy, 3.6 (2.3,
      5.8); blindness, 10.1 (3.2, 31.6); and peripheral neuropathy, 3.8 (2.7, 5.3). In
      multivariable models only age (2.1 [1.7, 2.5]), female sex, (1.9 [1.2, 2.8]) and
      macroalbuminuria (5.2 [2.9, 10.3]) remained significantly associated with
      subclinical grossly abnormal myocardial function. CONCLUSIONS/INTERPRETATION:
      Subclinical myocardial dysfunction is a common finding in type 1 diabetes
      patients without known heart disease. Type 1 diabetes patients with albuminuria
      are at greatly increased risk of having subclinical abnormal myocardial function
      compared with patients without albuminuria. Echocardiography may be particularly
      warranted in patients with albuminuria.

PMID- 24449395
TI  - Nutritional aspects of metabolic inflammation in relation to health--insights
      from transcriptomic biomarkers in PBMC of fatty acids and polyphenols.
AB  - Recent research has highlighted potential important interaction between
      metabolism and inflammation, within the context of metabolic health and
      nutrition, with a view to preventing diet-related disease. In addition to this,
      there is a paucity of evidence in relation to accurate biomarkers that are
      capable of reflecting this important biological interplay or relationship between
      metabolism and inflammation, particularly in relation to diet and health.
      Therefore the objective of this review is to highlight the potential role of
      transcriptomic approaches as a tool to capture the mechanistic basis of metabolic
      inflammation. Within this context, this review has focused on the potential of
      peripheral blood mononuclear cells transcriptomic biomarkers, because they are an
      accessible tissue that may reflect metabolism and subacute chronic inflammation.
      Also these pathways are often dysregulated in the common diet-related diseases
      obesity, type 2 diabetes, and cardiovascular disease, thus may be used as markers
      of systemic health. The review focuses on fatty acids and polyphenols, two
      classes of nutrients/nonnutrient food components that modulate
      metabolism/inflammation, which we have used as an example of a proof-of-concept
      with a view to understanding the extent to which transcriptomic biomarkers are
      related to nutritional status and/or sensitive to dietary interventions. We show
      that both nutritional components modulate inflammatory markers at the
      transcriptomic level with the capability of profiling pro- and anti-inflammatory
      mechanisms in a bidirectional fashion; to this end transcriptomic biomarkers may
      have potential within the context of metabolic inflammation. This transcriptomic
      biomarker approach may be a sensitive indicator of nutritional status and
      metabolic health. 

PMID- 24449396
TI  - Bridge-localized HOMO-binding character of divinylanthracene-bridged dinuclear
      ruthenium carbonyl complexes: spectroscopic, spectroelectrochemical, and
      computational studies.
AB  - The electronic properties of four divinylanthracene-bridged diruthenium carbonyl
      complexes [{RuCl(CO)(PMe3)3}2(MU-CH=CHArCH=CH)] (Ar=9,10-anthracene (1), 1,5
      anthracene (2), 2,6-anthracene (3), 1,8-anthracene (4)) obtained by molecular
      spectroscopic methods (IR, UV/Vis/near-IR, and EPR spectroscopy) and DFT
      calculations are reported. IR spectroelectrochemical studies have revealed that
      these complexes are first oxidized at the noninnocent bridging ligand, which is
      in line with the very small nu(C=O) wavenumber shift that accompanies this
      process and also supported by DFT calculations. Because of poor conjugation in
      complex 1, except oxidized 1(+), the electronic absorption spectra of complexes
      2(+), 3(+), and 4(+) all display the characteristic near-IR band envelopes that
      have been deconvoluted into three Gaussian sub-bands. Two of the sub-bands belong
      mainly to metal-to-ligand charge-transfer (MLCT) transitions according to results
      from time-dependent DFT calculations. EPR spectroscopy of chemically generated
      1(+)-4(+) proves largely ligand-centered spin density, again in accordance with
      IR spectra and DFT calculations results.

PMID- 24449392
TI  - Epigenetic epidemiology: promises for public health research.
AB  - Epigenetic changes underlie developmental and age related biology. Promising
      epidemiologic research implicates epigenetics in disease risk and progression,
      and suggests epigenetic status depends on environmental risks as well as genetic
      predisposition. Epigenetics may represent a mechanistic link between
      environmental exposures, or genetics, and many common diseases, or may simply
      provide a quantitative biomarker for exposure or disease for areas of
      epidemiology currently lacking such measures. This great promise is balanced by
      issues related to study design, measurement tools, statistical methods, and
      biological interpretation that must be given careful consideration in an
      epidemiologic setting. This article describes the promises and challenges for
      epigenetic epidemiology, and suggests directions to advance this emerging area of
      molecular epidemiology.

PMID- 24449399
TI  - International Skeletal Society outreach in Argentina.
AB  - From June 28th to 29th, 2013, the Argentinian ISS Outreach Program took place in
      collaboration with the Centro de Diagnostico Dr. Enrique Rossi in the city of
      Buenos Aires. A total of 690 participants attended. In the following report, we
      analyze the actual radiologic situation in this South American country. Outreach
      programs in a country such as Argentina are extremely valuable, as they provide a
      great opportunity for physicians that cannot travel overseas an attend
      international meetings such as RSNA, International Skeletal Society, or ARRS. 

PMID- 24449401
TI  - Whole-body MRI-based fat quantification: a comparison to air displacement
      plethysmography.
AB  - PURPOSE: To demonstrate the feasibility of an algorithm for MRI whole-body
      quantification of internal and subcutaneous fat and quantitative comparison of
      total adipose tissue to air displacement plethysmography (ADP). MATERIALS AND
      METHODS: For comparison with ADP, whole-body MR data of 11 volunteers were
      obtained using a continuously moving table Dixon sequence. Resulting fat images
      were corrected for B1 related intensity inhomogeneities before fat segmentation.
      RESULTS: The performed MR measurements of the whole body provided a direct
      comparison to ADP measurements. The segmentation of subcutaneous and internal fat
      in the abdomen worked reliably with an accuracy of 98%. Depending on the
      underlying model for fat quantification, the resultant MR fat masses represent an
      upper and a lower limit for the true fat masses. In comparison to ADP, the
      results were in good agreement with rho >= 0.97, P < 0.0001. CONCLUSION: Whole
      body fat quantities derived noninvasively by using a continuously moving table
      Dixon acquisition were directly compared with ADP. The accuracy of the method and
      the high reproducibility of results indicate its potential for clinical
      applications.

PMID- 24449400
TI  - A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and
      surgery refractory meningiomas.
AB  - When surgery and radiation are no longer treatment options, salvage systemic
      therapy has been used for recurrent meningiomas with little compelling evidence
      to suggest effectiveness. Patients with surgery and radiation refractory
      recurrent meningiomas were treated with the oral multifunctional tyrosine kinase
      inhibitor PTK787/ZK 222584 (PTK787) at a dose of 500 mg twice a day. Each
      treatment cycle was 4 weeks with MRI done every 8 weeks. Twenty-five patients (14
      men; 11 women) with a median age of 59 years and KPS of 80 were treated.
      Meningioma WHO Grade was I in 2 patients, II in 14 patients and III in 8
      patients; 1 patient had a hemangiopericytoma. All patients had prior surgery,
      external beam radiation therapy or radiosurgery and 11 patients prior systemic
      chemotherapy. Median number of cycles of PTK 787 administered was 4 (range <1
      22). Best response in the 22 evaluable patients was stable disease in 15 (68.2
      %). Predominant PTK787 related toxicities included fatigue (60 %), hypertension
      (24 %) and elevated transaminases (24 %). Grade II patients had a progression
      free survival (PFS)-6 of 64.3 %, a median PFS of 6.5 months and an overall
      survival (OS) of 26.0 months; grade III patients had a PFS-6 of 37.5 %, median
      PFS of 3.6 months and OS 23 months. PTK787 was modestly toxic at the dose of 500
      mg administered twice per day. Activity as determined by PFS-6 suggests that
      targeting PDGF/VEGF pathway warrants further investigation.

PMID- 24449402
TI  - The sensory thalamus and cerebral motor cortex are affected concurrently during
      induction of anesthesia with propofol: a case series with intracranial
      electroencephalogram recordings.
AB  - PURPOSE: Brain imaging studies suggest that loss of consciousness induced by
      general anesthetics is associated with impairment of thalamic function. There is,
      however, limited information on the time course of these changes. We recently
      obtained intracranial electroencephalogram (EEG) recordings from the
      ventroposterolateral (VPL) nucleus of the thalamus and from the motor cortex
      during induction of anesthesia in three patients to study the time course of the
      alterations of cortical and thalamic function. CLINICAL FEATURES: The patients
      were American Society of Anesthesiologists physical status I-II males aged 33-57
      yr with intractable central pain caused by brachial plexus injury (patient 1 and
      2) or insular infarct (patient 3). Anesthesia was induced with propofol (2.5-3.1
      mg.kg(-1) over 30-45 sec) followed, after loss of consciousness, by rocuronium
      for tracheal intubation. The data retained for analysis are from one minute
      before the start of propofol to 110 sec later during ventilation of the patients'
      lungs before tracheal intubation. Spectral analysis was used to measure absolute
      EEG power. Propofol caused significant increases of cortical and thalamic power
      in the delta to beta frequency bands (1-30 Hz). These increases of cortical and
      thalamic power occurred either concomitantly or within seconds of each other.
      Propofol also caused a decrease in cortical and thalamic high-gamma (62-200 Hz)
      power that also followed a similar time course. CONCLUSION: We conclude that
      induction of anesthesia with propofol in these patients was associated with
      concurrent alterations of cortical and sensory thalamic activity.

PMID- 24449405
TI  - Purification of chimeric heavy chain monoclonal antibody EG2-hFc using
      hydrophobic interaction membrane chromatography: an alternative to protein-A
      affinity chromatography.
AB  - Heavy chain monoclonal antibodies are being considered as alternative to whole
      IgG monoclonal antibodies for certain niche applications. Protein-A
      chromatography which is widely used for purifying IgG monoclonal antibodies is
      also used for purifying heavy chain monoclonal antibodies as these molecules
      possess fully functional Fc regions. However, the acidic conditions used to elute
      bound antibody may sometimes also leach protein-A, which is immunotoxic. Low pH
      conditions also tend to make the mAb molecules unstable and prone to aggregation.
      Moreover, protein-A affinity chromatography does not remove aggregates already
      present in the feed. Hydrophobic interaction membrane chromatography (or HIMC)
      has already been studied as an alternative to protein-A chromatography for
      purifying whole-IgG monoclonal antibodies. This paper describes the use of HIMC
      for capturing a humanized chimeric heavy chain monoclonal antibody (EG2-hFC).
      Binding and eluting conditions were suitably optimized using pure EG2-hFC. Based
      on this, an HIMC method was developed for capture of EG2-hFC directly from cell
      culture supernatant. The EG2-hFc purity obtained in this single-step process was
      high. The glycan profiles of protein-A and HIMC purified monoclonal antibody
      samples were similar, clearly demonstrating that both techniques captured
      similarly glycosylated population of EG2-hFc. Moreover, this technique was able
      to resolve aggregates from monomeric form of the EG2-hFc.

PMID- 24449406
TI  - Cerium-based M4L4 tetrahedra as molecular flasks for selective reaction prompting
      and luminescent reaction tracing.
AB  - The application of metal-organic polyhedra as "molecular flasks" has precipitated
      a surge of interest in the reactivity and property of molecules within well
      defined spaces. Inspired by the structures of the natural enzymatic pockets,
      three metal-organic neutral molecular tetrahedral, Ce-TTS, Ce-TNS and Ce-TBS
      (H6TTS: N',N'',N'''-nitrilotris-4,4',4''-(2-hydroxybenzylidene)-benzohydrazide;
      H6TNS: N',N'',N'''-nitrilotris-6,6',6''-(2-hydroxybenzylidene)-2
      naphthohydrazide; H6TBS: 1,3,5-phenyltris-4,4',4''-(2
      hydroxybenzylidene)benzohydrazide), which exhibit different size of the edges and
      cavities, were achieved through self-assembly by incorporating robust amide
      containing tridentate chelating sites into the fragments of the ligands. They
      acted as molecular flasks to prompt the cyanosilylation of aldehydes with
      excellent selectivity towards the substrates size. The amide groups worked as
      trigger sites and catalytic driven forces to achieve efficient guest
      interactions, enforcing the substrates proximity within the cavity. Experiments
      on catalysts with the different cavity radii and substrates with the different
      molecular size demonstrated that the catalytic performance exhibited enzymatical
      catalytic mechanism and occurred in the molecular flask. These amides were also
      able to amplify guest-bonding events into the measurable outputs for the
      detection of concentration variations of the substrates, providing the
      possibility for metal-organic hosts to work as smart molecular flasks for the
      luminescent tracing of catalytic reactions.

PMID- 24449403
TI  - ITPA genotype protects against anemia during peginterferon and ribavirin therapy
      but does not influence virological response.
AB  - On-treatment anemia is associated with higher sustained virological response
      (SVR) rates during peginterferon plus ribavirin (RBV) therapy. Inosine
      triphosphatase (ITPA) variants causing ITPase deficiency have been shown to
      protect against RBV-induced anemia. However, ITPase activity has not been
      associated with SVR. To study this discrepancy, we examined the relationships
      between ITPase activity, on-treatment anemia, SVR, and RBV levels in hepatitis C
      virus genotype 1 (HCV-1) patients from the CHARIOT study. ITPA genotype
      (rs7270101, rs1127354) was used to define ITPase activity in 546 patients. Plasma
      RBV levels were measured using high-performance liquid chromatography (HPLC).
      Relationships between ITPase activity, on-treatment hemoglobin (Hb) levels, RBV
      levels, and SVR were tested using regression modeling, survival analysis, and
      locally weighted scatterplot smoothing (LOWESS) plot analysis. Hb decline was
      independently associated with SVR (P<0.0001). ITPase deficiency was present in
      35%. ITPase deficiency strongly protected against Hb decline (P<0.0001), but was
      not associated with SVR (P=0.28). The probability of SVR increased with lower
      nadir Hb for both wild-type and deficient ITPase activity, but the association
      curve shifted to describe a parallel relationship at higher Hb levels in patients
      with ITPase deficiency. In a subset (n=203), we tested the hypothesis that the
      association between Hb decline and SVR reflected RBV levels rather than actual Hb
      level. RBV levels were associated with on-treatment Hb decline and SVR, but not
      ITPase activity. In regression models, adjustment for RBV levels attenuated the
      association between Hb decline and SVR. CONCLUSION: ITPase deficiency protects
      against RBV-induced anemia, but is not associated with SVR. Our data suggest that
      the relationship between Hb decline and SVR is not mechanistic, but is linked to
      RBV levels.

PMID- 24449404
TI  - Imbalance in redox status is associated with tumor aggressiveness and poor
      outcome in lung adenocarcinoma patients.
AB  - PURPOSE: The expression levels of human antioxidant genes (HAGs) and oxidative
      markers were investigated in light of lung adenocarcinoma aggressiveness and
      patient outcome. METHODS: We assayed in vitro the tumoral invasiveness and
      multidrug resistance in human lung adenocarcinoma (AdC) cell lines (EKVX and
      A549). Data were associated with several redox parameters and differential
      expression levels of HAG network. The clinicopathological significance of these
      findings was investigated using microarray analysis of tumor tissue and by
      immunohistochemistry in archival collection of biopsies. RESULTS: An overall
      increased activity (expression) of selected HAG components in the most aggressive
      cell line (EKVX cells) was observed by bootstrap and gene set enrichment analysis
      (GSEA). In vitro validation of oxidative markers revealed that EKVX cells had
      high levels of oxidative stress markers. In AdC cohorts, GSEA of microarray
      datasets showed significantly high levels of HAG components in lung AdC samples
      in comparison with normal tissue, in advanced stage compared with early stage and
      in patients with poor outcome. Cox multivariate regression analysis in a cohort
      of early pathologic (p)-stage of AdC cases showed that patients with moderate
      levels of 4-hydroxynonenal, a specific and stable end product of lipid
      peroxidation, had a significantly less survival rate (hazard ratio of 8.87) (P <
      0.05). CONCLUSIONS: High levels of oxidative markers are related to tumor
      aggressiveness and can predict poor outcome of early-stage lung adenocarcinoma
      patients.

PMID- 24449407
TI  - Comparison of statins and apples was unfair.

PMID- 24449408
TI  - Polypoid changes of the middle turbinate as an indicator of atopic disease.
AB  - BACKGROUND: High levels of local immunoglobulin E (IgE) have been demonstrated in
      nasal polypoid tissue; however, an association between nasal polyps and allergy
      has not been proven. The authors have observed that polypoid edema isolated to
      the leading edge of the middle turbinate (MT) is highly associated with allergic
      rhinitis. The objective of this study was to determine if there is an association
      between isolated MT polyps and inhalant allergy. METHODS: A single institution
      prospective study was performed. Twenty-five consecutive patients found to have
      isolated MT polyps on endoscopic exam were recruited. Nasal and allergy symptoms
      were documented on the intake form. Allergy testing was recommended to all
      patients. RESULTS: Of the 25 patients found to have isolated MT polypoid edema
      documented on endoscopic exam, 16 patients underwent skin or in vitro allergy
      testing. All of the patients tested positive for inhalant allergy. CONCLUSION:
      This small series provides strong evidence to support an association between
      isolated MT polypoid edema and allergy. We recommend allergy testing in all
      patients with isolated MT polyps or polypoid edema.

PMID- 24449409
TI  - NogoR1 and PirB signaling stimulates neural stem cell survival and proliferation.
AB  - Neural stem cells (NSCs) and neural progenitors (NPs) in the mammalian neocortex
      give rise to the main cell types of the nervous system. The biological behavior
      of these NSCs and NPs is regulated by extracellular niche derived autocrine
      paracrine signaling factors on a developmental timeline. Our previous reports
      [Plos One 2010;5:e15341; J Neurochem 2011;117:565-578] have shown that
      chondroitin sulfate proteoglycan and ApolipoproteinE are autocrine-paracrine
      survival factors for NSCs. NogoA, a myelin related protein, is expressed in the
      cortical ventricular zones where NSCs reside. However, the functional role of
      Nogo signaling proteins in NSC behavior is not completely understood. In this
      study, we show that NogoA receptors, NogoR1 and PirB, are expressed in the
      ventricular zone where NSCs reside between E10.5 and 14.5 but not at E15.5. Nogo
      ligands stimulate NSC survival and proliferation in a dosage-dependent manner in
      vitro. NogoR1 and PirB are low and high affinity Nogo receptors, respectively and
      are responsible for the effects of Nogo ligands on NSC behavior. Inhibition of
      autocrine-paracrine Nogo signaling blocks NSC survival and proliferation. In
      NSCs, NogoR1 functions through Rho whereas PirB uses Shp1/2 signaling pathways to
      control NSC behavior. Taken together, this work suggests that Nogo signaling is
      an important pathway for survival of NSCs.

PMID- 24449410
TI  - Chromosomal effects of non-alkylating drug exposure in oncology personnel.
AB  - Therapy-related leukemia has been a recognized sequela of cancer treatment for
      decades with "signature" abnormalities of chromosomes 5, 7, and 11 observed in
      treated patients. Risk to oncology personnel handling anti-cancer agents has also
      been documented by non-specific measures of genotoxicity in blood and urine.
      Using chromosomal markers applied in clinical practice, we previously
      demonstrated in oncology workers, a dose-related increase in abnormalities of
      chromosomes 5 and 7, known to be targets of alkylating agent exposure. In the
      analysis presented here, we extended that work to also assess damage resulting
      from non-alkylating drug exposure. Peripheral blood lymphocytes from oncology
      personnel (N = 63) and non-exposed controls (N = 46) was collected and examined
      using the fluorescent in situ hybridization technique with probes for targets on
      chromosomes 5, 7, and 11. Participants recorded drug handling events over a 6
      week period. Important co-variates were considered. Examining chromosomal
      outcomes as a function of drug handling frequency, we employed Poisson Regression
      to obtain incident rate ratios (IRRs) for selected drug handling frequencies. We
      found a dose-related increase in the IRR for aberrations in all three chromosomes
      5, 7, and 11, reaching statistical significance for chromosome 5, as a function
      of non-alkylating drug handling. This suggests that the targeting of chromosome 5
      is not limited to alkylating agent exposure, as some recent evidence in treated
      patients has also shown. Thus, the pattern of insult observed in treated patients
      appears to extend to oncology personnel exposed in the workplace.

PMID- 24449411
TI  - Surgical resident experience in breast disease: a national study.
AB  - BACKGROUND: Management of breast disease is an integral component of general
      surgery. This study was performed to describe the exposure to breast disease by
      residents in Canadian general surgery programs. METHODS: This study involved a 20
      item survey and pilot semistructured interviews. Surgical trainees at 12 training
      programs in Canada participated in the survey. Results were used to characterize
      resident experience with breast surgery and clinics. RESULTS: Residents across
      all post-graduate training years and from 12 Canadian medical schools responded
      (n = 162, 44 %). Residents had the most breast surgery experience in PGY2 and
      PGY3 years. One third of trainees performed <= 1 breast procedure per month. Only
      25 % had attended more than one breast clinic per month. Lumpectomies were the
      most common procedure (20.7/year) and 94 % of residents performed sentinel lymph
      node biopsy. Four pilot semistructured interviews were performed. The greatest
      stated barriers to breast training were "lack of time" and the impression that
      these were "lower priority cases." CONCLUSIONS: Achieving competence in breast
      disease management is a key requirement for general surgery trainees. Surgical
      educators must ensure that the quality and quantity of residency training in
      breast diseases is sufficient for future surgeons to provide optimal patient
      care.

PMID- 24449412
TI  - Understanding the burden and outcome of trauma care drives a new trauma systems
      model.
AB  - BACKGROUND: The Pietermaritzburg Metropolitan Trauma Service (PMTS) attempts to
      provide care for a whole city and hence is referred to as a service rather than a
      center. As part of a multifaceted quality improvement program, the PMTS has
      developed and implemented a robust electronic surgical registry (ESR). This
      review of the first year's data from the ESR forms part of a situational analysis
      to assess the burden of trauma managed by the service and the quality of care
      delivered within the constraints of the available resources. METHODS: Formal
      ethical approval was obtained prior to design and development of this study, and
      appropriate commercial software was sourced. The exercise of data capture was
      integrated into the process of service delivery and was accomplished at the
      endpoint of patient care. 12 months after implementation of the registry, the
      data were extracted and audited. RESULTS: A total of 2,733 patients were admitted
      over the 12 month study period. The average patient age was 28.3 years. There
      were 2,255 (82.5 %) male patients and 478 (17.5 %) female patients. The average
      monthly admission rate was 228 patients, with a peak of 354 admissions over the
      December period. The mean injury severity score (ISS) was 12 [interquartile range
      (IQR) 6.7-23.2]. A quarter (24.8 %) of all new emergency admissions had an ISS >
      15. The average duration of stay for patients was 5.12 days (IQR 2.3-13.2 days).
      Some 2,432 (92.1 %) patients survived, and 208 (7.9 %) died. A total of 333 (13
      %) patients required admission to either the intensive care unit (ICU) or the
      high dependency unit. From the city mortuary data a further 362 deaths were
      identified. These included 290 deaths that occurred on scene and 72 that occurred
      within Pietermaritzburg hospitals other than Greys and Edendale. The total trauma
      related mortality for the entire city in 2012 was 570 (51 % on-scene deaths and
      49 % in-hospital deaths). Blunt trauma accounted for 62 % of deaths. CONCLUSIONS:
      The PMTS treats a significant volume and spectrum of trauma. Despite significant
      resource limitations, we have managed to implement a functional and sustainable
      trauma service across multiple hospitals. We believe the major resource deficits
      limiting our service could be ameliorated by the development of an additional
      trauma facility, adequately equipped with dedicated trauma operating slates and
      trauma ICU beds. The adoption of our current model of trauma care came out of a
      need to work within our resource constraints, and it differs from the traditional
      model. Within the aforementioned limits, our data suggest that this model of
      delivering care is feasible, practical, and successful. Considering the universal
      burden of trauma and the all-too-common imbalance between resource demand and
      supply among many health-care institutions, it is our hope that this report will
      contribute to the ongoing academic debate around the topic of optimal systems of
      providing global trauma care.

PMID- 24449413
TI  - Heterogeneity of colon cancer patients reported as emergencies.
AB  - BACKGROUND: Up to one-fourth of all colon cancer patients are reported as
      emergencies, and the aim of the present study was to scrutinize mode of
      presentation in this group. MATERIALS AND METHODS: All reported cases of
      emergency (n = 263) and randomly selected elective controls (1:2) of colon cancer
      in four Swedish counties 2006-2008 were eligible (n = 854). Symptoms and aspects
      of management were retrieved from surgery and primary care records. Outcomes were
      compared using Kaplan-Meier estimates and Cox regression. RESULTS: Among patients
      reported as emergencies, 158/263 (60 %) underwent operation within three days
      (acute), and 105 (40 %) after more than 3 days (subacute). In the latter group,
      20/94 (21 %) had reported two symptoms, and 31/94 (33 %) had reported three or
      more symptoms associated with colon cancer to primary care during the last 12
      months prior to surgery. In total, 46/105 (44 %) had already had an examination
      of the large bowel, and 52/105 (50 %) were stage IV, as opposed to 36/158 (23 %)
      in the acute group and 83/577 (15 %) in the elective group (p < 0.001). Mortality
      at 30 and 90 days was 15.2 and 35.6 % in the subacute group, 8.2 and 14.9 % in
      the acute group (p = 0.001), and 1.9 and 4.3 % in the elective group (p < 0.001);
      5-year survival was 28.3, 40.1, and 57.8 %, respectively, in the three groups (p
      < 0.001). The hazard ratio, adjusted for age, sex, and stage, was 1.88 95 %
      confidence interval (CI) 1.5-2.4) for the acute group and 2.29 (95 % CI 1.7-3.1)
      for the subacute group. CONCLUSIONS: Colon cancer patients reported as
      emergencies but operated upon more than three days after admission had the worst
      outcome. Efforts to decrease the interval between admission and surgery is one
      important aspect of care, but wider attention must also be paid to this group of
      patients.

PMID- 24449415
TI  - Educational benefits of fusing magnetic resonance imaging with sonograms.
AB  - PURPOSE: To investigate whether providing sonographic (US)/MRI fusion images will
      enhance the ability of medical students and radiology residents to identify MSK
      anatomy on sonograms alone. METHODS: Medical students (n = 31) and radiology
      residents (n = 23) were each randomly divided into two groups: Group A and Group
      B. Subjects in Group A were shown 10 MSK sonograms with arrows pointing to a
      specific anatomic structure or anatomic region. Subjects in Group B were shown
      the exact same 10 annotated sonograms as Group A as well as an additional fusion
      image consisting of an MRI of the same anatomy in the same plane fused with the
      sonogram without arrows. Sonograms and MRI were obtained from adult patients who
      consented to have their images used. The anatomic regions included the shoulder,
      hip, and pelvis. Both groups were given the same 10-question multiple choice
      examination to identify the anatomic structure that the arrow was marking on the
      sonogram. The transducer's location was given for every question. One minute was
      allowed to answer each question. The Wilcoxon rank sum test was used to assess if
      there was a difference between Group A and Group B in both the medical student
      and the radiology resident cohorts. RESULTS: Medical students: subjects in Group
      A (n = 16) gave the correct answers in 33.8% of the cases (54/160). Subjects in
      Group B (n = 15) gave correct answers in 26.0% of the cases (39/150) (p value
      <0.110). Radiology residents: subjects in Group A (n = 11) gave correct answers
      in 40.9% of the cases (45/110). Subjects in Group B (n = 12) gave correct answers
      in 72.5% of the cases (87/120) (p value <0.001). CONCLUSION: The addition of a
      fusion MRI/US image enhances radiology residents' ability to identify MSK US
      anatomy accurately compared with the sonogram alone. The medical students,
      however, did not show improvement with the addition of the fusion MRI/sonogram.
      2014.

PMID- 24449414
TI  - Minimizing preventable trauma deaths in a limited-resource setting: a test-case
      of a multidisciplinary panel review approach at the Komfo Anokye Teaching
      Hospital in Ghana.
AB  - OBJECTIVE: Our objectives were to determine the proportion of preventable trauma
      deaths at a large trauma hospital in Kumasi, Ghana, and to identify opportunities
      for the improvement of trauma care. METHODS: A multidisciplinary panel of experts
      evaluated pre-hospital, hospital, and postmortem data of consecutive trauma
      patients who died over a 5-month period in 2006-2007 at the Komfo Anokye Teaching
      Hospital. The panel judged the preventability of each death. For preventable and
      potentially preventable deaths, deficiencies in care that contributed to their
      deaths were identified. RESULTS: The panel reviewed 231 trauma deaths. Of these,
      84 charts had sufficient information to review preventable factors. The panel
      determined that 23 % of trauma deaths were definitely preventable, 37 % were
      potentially preventable, and 40 % were not preventable. One main deficiency in
      care was identified for each of the 50 definitely preventable and potentially
      preventable deaths. The most common deficiencies were pre-hospital delays (44 %
      of the 50 deficiencies), delay in treatment (32 %), and inadequate fluid
      resuscitation (22 %). Among the 19 definitely preventable deaths, the most common
      cause of death was hemorrhage (47 %), and the most common deficiencies were
      inadequate fluid resuscitation (37 % of deficiencies in this group) and pre
      hospital delay (37 %). CONCLUSIONS: A high proportion of trauma fatalities might
      have been preventable by decreasing pre-hospital delays, adequate resuscitation
      in hospital, and earlier initiation of care, including definitive surgical
      management. The study also showed that preventable death panel reviews are a
      feasible and useful quality improvement method in the study setting.

PMID- 24449416
TI  - Antimicrobial potentials of active component isolated from Citrullus colocynthis
      fruits and structure-activity relationships of its analogues against foodborne
      bacteria.
AB  - BACKGROUND: Synthetic preservatives have been consistently used to maintain the
      quality of food products. However, the degree of danger to human health cannot be
      ignored. In this study, the antimicrobial activities of Citrullus colocynthis
      fruits and 4-methylquinoline analogues were investigated to develop natural
      preservatives against foodborne bacteria. RESULTS: Antimicrobial activities of
      the methanol extract and five fractions derived from C. colocynthis fruits were
      evaluated against five foodborne bacteria. The chloroform fraction possessed
      strong activities against five foodborne bacteria. 4-Methylquinoline was isolated
      by chromatographic analyses. To establish the structure-activity relationships,
      the antimicrobial activities of 4-methylquinoline analogues (2-hydroxyquinoline,
      4-hydroxyquinoline, 6-hydroxyquinoline, 2-methylquinoline, 6-methyquinoline, 8
      methylquinoline and 2-methyl-8-hydroxyquinoline) were tested against food-borne
      bacteria. When employing the agar diffusion method, 2-methyl-8-hydroxyquinoline
      was found to have potent activities against the five foodborne bacteria. In terms
      of minimum bactericidal concentration or minimum inhibitory concentration, 2
      methyl-8-hydroxyquinoline had significantly higher antimicrobial activity against
      the five foodborne bacteria. CONCLUSION: Citrullus colocynthis fruits and 4
      methylquinoline analogues could be useful for the development of eco-friendly
      food supplemental agents and pharmaceuticals.

PMID- 24449417
TI  - In vitro enhancement of mouse T helper 2 cell sensitization to ovalbumin allergen
      by carbon black nanoparticles.
AB  - Agglomerated carbon black nanoparticles (CBNPs) administered via respiratory or
      subcutaneous routes have been shown to promote allergic sensitization to
      coadministered ovalbumin (OVA) protein in rodents. In the present study, we aimed
      to model and elucidate the mechanism of this adjuvanticity using an in vitro
      assay based on T cell sensitization to ovalbumin323-339 peptide (OVA(p)). CBNP
      base particles of 22 and 39 nm were characterized and termed CBNP22 and CBNP39
      powders. Splenic leukocytes derived from transgenic DO11.10 mice were exposed to
      suspensions of media alone, concanavalin A mitogen, CBNP agglomerates smaller
      than 220 nm, OVA(p) alone, OVA(p) + anti-CD28 costimulant, OVA(p) + cyclosporin A
      immunosuppressant, or OVA(p) + CBNPs. Samples were analyzed at 72 h post
      exposure. Proliferation rate, a marker of cellular mitosis, was assessed.
      Polymerase chain reaction arrays were used to assess genes involved in allergic
      response pathways. The mitogen control, costimulatory control, and
      immunosuppressive control chemicals modified the T helper cell proliferation
      rate. CBNP22 mildly reduced proliferation at 12 MUg/ml, but CBNP39 did not. Gene
      expression analysis of cells treated with OVA(p) showed that coincubation with 12
      MUg/ml CBNP22 enhanced gene expression of interleukin-4 (IL-4), IL-10, and IL-13,
      all allergy-associated Th2 cytokines. Coincubation of OVA(p) with 12 MUg/ml
      CBNP39 significantly enhanced IL-13 gene expression concurrent with
      downregulation of the Th1-associated transcription factor Stat4. IL-4 and IL-13
      protein secretion reflected the mRNA trends. The changes were consistently higher
      in cells exposed to CBNP22 than CBNP39, suggesting that smaller particle size,
      higher surface area, and higher purity were associated with the direct adjuvant
      effect on Th2 cells in this genetically susceptible model of OVA allergy.

PMID- 24449418
TI  - Dysfunction of vascular smooth muscle and vascular remodeling by simvastatin.
AB  - Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are
      widely prescribed for hypercholesterolemia. With the increasing use of statins,
      numerous reports demonstrated that statins can cause damage to skeletal muscles.
      However, the toxicities of statins on vascular smooth muscle, which are essential
      to cardiovascular homeostasis, have not been previously described. Here, we
      examined the effects of simvastatin on the contractile function and the integrity
      of vascular smooth muscle in isolated rat thoracic aortic rings, primary cultured
      vascular smooth muscle cells (VSMCs) in vitro and rats in vivo. In aortic rings,
      simvastatin suppressed the normal agonist-induced contractile responses in time-
      and concentration-dependent manners (0.86 g +/- 0.11 at 10 MUM simvastatin for 24
      h compared with 1.89 g +/- 0.11 at control). The suppression persisted in the
      endothelium-denuded aortic rings and was irreversible even after wash-out of
      simvastatin. Simvastatin suppressed the contraction induced by Bay K8644, an
      activator of voltage-operated Ca2+ channel (VOCC) in rat aortic rings and
      abolished agonist-induced intracellular Ca2+ increase in VSMCs. The simvastatin
      induced contractile dysfunction was reversed by the supplementation of mevalonate
      and geranylgeranylpyrophosphate, precursors for protein isoprenylation.
      Consistently, activation of RhoA, a representative isoprenylated protein, was
      disrupted by simvastatin in VSMCs and RhoA-mediated phosphorylation of MYPT1 and
      CPI-17, and tonic tension were also suppressed. Notably, prolonged treatment of
      simvastatin up to 48 h induced apoptosis of vascular smooth muscle in aortic
      rings. Most importantly, simvastatin treatment in vivo significantly attenuated
      the agonist-induced vasoconstriction in rats ex vivo and induced a decrease in
      luminal area of the vascular wall. Collectively, these results demonstrate that
      simvastatin can impair the normal vascular contractility by disturbing Ca2+
      influx and RhoA activity, ultimately leading to apoptosis and structural
      remodeling.

PMID- 24449419
TI  - Cadmium selectively induces MIP-2 and COX-2 through PTEN-mediated Akt activation
      in RAW264.7 cells.
AB  - Increasing evidence demonstrates that cadmium (Cd) induces inflammation, but its
      mechanisms remain obscure. The present study showed that treatment with CdCl2
      selectively upregulates macrophage inflammatory protein (MIP)-2 and
      cyclooxygenase (COX)-2 in RAW264.7 cells. Concomitantly, Cd2+ markedly elevated
      the level of phosphorylated Akt in dose- and time-dependent manners. LY294002, a
      specific inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked Cd2+-evoked
      Akt phosphorylation. Correspondingly, LY294002 significantly repressed Cd2+
      induced upregulation of MIP-2 and COX-2 in RAW264.7 cells. Further experiments
      showed that treatment with Cd2+ significantly reduced the level of PTEN protein
      in RAW264.7 cells. MG132, a specific proteasome inhibitor, blocked Cd2+-induced
      reduction in PTEN protein as well as Akt phosphorylation, implicating the
      involvement of proteasome-mediated PTEN degradation. Of interest, Cd2+-induced
      degradation of PTEN protein appears to be associated with PTEN ubiquitination. N
      acetylcysteine, a glutathione (GSH) precursor, blocked Cd2+-evoked PTEN
      degradation as well as Akt phosphorylation. By contrast, L-buthionine-S,R
      sulfoximine, an inhibitor of cellular GSH synthesis, exacerbated Cd2+-induced
      PTEN degradation and Akt phosphorylation. Alpha-phenyl-N-tert-butylnitrone and
      vitamin C, two antioxidants, did not prevent from Cd2+-induced PTEN degradation
      and Akt phosphorylation. In conclusion, Cd2+ selectively induces MIP-2 and COX-2
      through PTEN-mediated PI3K/Akt activation. Cellular GSH depletion mediates Cd2+
      induced PTEN degradation and subsequent PI3K/Akt activation in macrophages.

PMID- 24449421
TI  - Ioxynil and tetrabromobisphenol A suppress thyroid-hormone-induced activation of
      transcriptional elongation mediated by histone modifications and RNA polymerase
      II phosphorylation.
AB  - To elucidate molecular mechanisms by which the phenolic herbicide ioxynil (IOX)
      and the brominated flame retardant tetrabromobisphenol A (TBBPA) exert thyroid
      hormone (TH) disrupting activity, we investigated the effects of the chemicals on
      the histone and RNA polymerase II (RNAPII) modifications in Xenopus laevis XL58
      TRE-Luc cells in direct TH-response genes encoding TH receptor beta (Thrb) and TH
      induced basic leucine zipper protein (Thibz) using chromatin immunoprecipitation
      assays. For both the thrb and thibz genes, 3,3',5-triiodothyronine (T3) enhanced
      the amounts of gene transcripts and increased the amounts of acetylated histone
      H4 (H4Ac), trimethylated histone H3 lysine 4 (H3K4me3) and phosphorylated RNAPII
      serine 5 (RNAPIIS5P), epigenetic markers of gene activation at 5' regulatory
      regions, and the amounts of trimethylated histone H3 lysine 36 (H3K36me3) and
      phosphorylated RNAPII serine 2 (RNAPIIS2P), epigenetic markers of activation of
      transcriptional elongation at protein coding regions. Treatment with IOX and
      TBBPA reduced the amounts of the thrb transcript and suppressed the T3-induced
      modifications of H3K4me3, RNAPIIS5P, H3K36me3, and RNAPIIS2P. In the thibz gene,
      IOX and TBBPA did not suppress the T3-induced histone and RNAPII modifications
      except for H3K36me3 in the TBBPA treatment, despite both chemicals decreasing the
      T3-induced transcription. Our results demonstrate that IOX and TBBPA affect TH
      induced histone and RNAPII modifications, which are involved in early and
      progressive stages of RNAPII transcriptional elongation, in direct TH-response
      genes, in somewhat target gene-dependent and chemical-specific manners. Both IOX
      and TBBPA are likely to influence epigenetically a cascade of TH receptor
      mediated gene regulation. 

PMID- 24449420
TI  - Rosiglitazone causes cardiotoxicity via peroxisome proliferator-activated
      receptor gamma-independent mitochondrial oxidative stress in mouse hearts.
AB  - This study aims to test the hypothesis that thiazolidinedione rosiglitazone
      (RSG), a selective peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonist, causes cardiotoxicity independently of PPARgamma. Energy metabolism and
      mitochondrial function were measured in perfused hearts isolated from C57BL/6,
      cardiomyocyte-specific PPARgamma-deficient mice, and their littermates. Cardiac
      function and mitochondrial oxidative stress were measured in both in vitro and in
      vivo settings. Treatment of isolated hearts with RSG at the supratherapeutic
      concentrations of 10 and 30 MUM caused myocardial energy deficiency as evidenced
      by the decreases in [PCr], [ATP], ATP/ADP ratio, energy charge with a concomitant
      cardiac dysfunction as indicated by the decreases in left ventricular systolic
      pressure, rates of tension development and relaxation, and by an increase in end
      diastolic pressure. When incubated with tissue homogenate or isolated
      mitochondria at these same concentrations, RSG caused mitochondrial dysfunction
      as evidenced by the decreases in respiration rate, substrate oxidation rates, and
      activities of complexes I and IV. RSG also increased complexes I- and III
      dependent O2- production, decreased glutathione content, inhibited superoxide
      dismutase, and increased the levels of malondialdehyde, protein carbonyl, and 8
      hydroxy-2-deoxyguanosine in mitochondria, consistent with oxidative stress. N
      acetyl-L-cysteine (NAC) 20 mM prevented RSG-induced above toxicity at those in
      vitro settings. Cardiomyocyte-specific PPARgamma deletion and PPARgamma
      antagonist GW9662 did not prevent the observed cardiotoxicity. Intravenous
      injection of 10 mg/kg RSG also caused cardiac dysfunction and oxidative stress,
      600 mg/kg NAC antagonized these adverse effects. In conclusion, this study
      demonstrates that RSG at supratherapeutic concentrations causes cardiotoxicity
      via a PPARgamma-independent mechanism involving oxidative stress-induced
      mitochondrial dysfunction in mouse hearts.

PMID- 24449422
TI  - Dose-response modeling of early molecular and cellular key events in the CAR
      mediated hepatocarcinogenesis pathway.
AB  - Low-dose extrapolation and dose-related transitions are paramount in the ongoing
      debate regarding the quantification of cancer risks for nongenotoxic carcinogens.
      Phenobarbital (PB) is a prototypical nongenotoxic carcinogen that activates the
      constitutive androstane receptor (CAR) resulting in rodent liver tumors. In this
      study, male and female CD-1 mice administered dietary PB at 0, 0.15, 1.5, 15, 75,
      or 150 mg/kg-day for 2 or 7 days to characterize multiple apical and molecular
      endpoints below, at (~75 mg/kg-day), and above the carcinogenic dose level of PB
      and examine these responses using benchmark dose modeling. Linear toxicokinetics
      were observed for all doses. Increased liver weight, hepatocellular hypertrophy,
      and mitotic figures were seen at 75 and 150 mg/kg-day. CAR activation, based on
      Cyp2b qPCR and pentoxyresorufin dealkylase activity, occurred at doses >= 1.5
      mg/kg-day. The no-observable transcriptional effect level for global gene
      expression was 15 mg/kg-day. At 2 days, several xenobiotic metabolism and cell
      protective pathways were activated at lower doses and to a greater degree in
      females. However, hepatocellular proliferation, quantified by bromodeoxyuridine
      immunohistochemistry, was the most sensitive indicator of PB exposure with female
      mice more sensitive than males, contrary to sex-specific differences in
      sensitivity to hepatocarcinogenesis. Taken together, the identification of low
      dose cellular and molecular transitions in the subtumorigenic dose range aids the
      understanding of early key events in CAR-mediated hepatocarcinogenesis. 

PMID- 24449423
TI  - Assessment of temporal dose-toxicity relationship of fumed silica nanoparticle in
      human lung A549 cells by conventional cytotoxicity and 1H-NMR-based extracellular
      metabonomic assays.
AB  - As nanoparticles could form aggregates in biological systems, the dynamics of
      their dispersity drives the temporal effect of nanoparticles in vitro. To test
      this hypothesis, the fumed silica nanoparticles (SiNPs) that have primary sizes
      of 7-14 nm and form aggregates in culture medium were selected for toxicity study
      in human lung A549 cells. The dispersity of SiNPs was analyzed by dynamic light
      scattering and transmission of electron microscopy. Cytotoxicity assays including
      mitochondrial activity, intracellular level of reactive oxygen species (ROS), and
      membrane damage together with the 1H-NMR-based extracellular metabonomic assay
      were conducted to determine the temporal dose-effect relationship of SiNPs. In
      cell culture medium, SiNPs dispersed well initially at 25-100 MUg/ml; however,
      they sedimented rapidly in a concentration-dependent manner. SiNPs caused a dose
      dependent increase of intracellular ROS and cell membrane damage at 4 h and a
      loss of cell viability after 48 h. SiNPs also induced an elevation of
      extracellular glucose, lactate, phenylalanine, histidine, and tyrosine levels in
      a time- and concentration-dependent manner. The dose-effect patterns at 4 h were
      different from that at 12 and 24 h as assessed by both cytotoxicity and
      metabonomic assays. Both fitted better with polynomial regression than linear
      regression, implying multimode action of SiNPs at different concentrations. The
      early NP-cell interaction and the late sedimentation could be attributable to the
      temporal effects of SiNPs. The extracellular 1H-NMR-based metabonomics
      demonstrated a potential as a robust nondestructive tool for monitoring the
      temporal effect of NPs that tend to aggregate in nature.

PMID- 24449424
TI  - Metabolomic analysis reveals metabolic changes caused by bisphenol A in rats.
AB  - Bisphenol A (BPA) is a widely used material known to cause adverse effects in
      humans and other mammals. To date, little is known about the global metabolomic
      alterations caused by BPA using urinalysis. Sprague-Dawley rats were orally
      administrated BPA at the levels of 0, 0.5 MUg/kg/day and 50 mg/kg/day covering a
      low dose and a reference dose for 8 weeks. We conducted a capillary
      electrophoresis in tandem with electrospray ionization time-of-flight mass
      spectrometry based nontargeted metabolomic analysis using rat urine. To verify
      the metabolic alteration at both low and high doses, reverse transcription
      polymerase chain reaction (RT-PCR) and western blotting were further conducted to
      analyze hepatic expression of methionine adenosyltransferase Ialpha (Mat1a) and
      methionine adenosyltransferase IIalpha (Mat2a). Hepatic S-adenosylmethionine
      (SAMe) was also analyzed. A total of 199 metabolites were profiled. Statistical
      analysis and pathway mapping indicated that the most significant metabolic
      perturbations induced by BPA were the increased biotin and riboflavin excretion,
      increased synthesis of methylated products, elevated purine nucleotide
      catabolism, and increased flux through the choline metabolism pathway. We found
      significantly higher mRNA and protein levels of Mat1a and Mat2a, and
      significantly higher SAMe levels in rat liver at both low and high doses. These
      two genes encode critical isoenzymes that catalyze the formation of SAMe, the
      principal biological methyl donor involved in the choline metabolism. In
      conclusion, an elevated choline metabolism is underlying the mechanism of highly
      methylated environment and related metabolic alterations caused by BPA. The data
      of BPA-elevated accepted biomarkers of injury indicate that BPA induces DNA
      methylation damage and broad protein degradation, and the increased deleterious
      metabolites in choline pathway may also be involved in the toxicity of BPA. 

PMID- 24449425
TI  - Psammomatoid Juvenile Ossifying Fibroma of the Maxilla: Radical Surgery with
      Maxillary Resection in a 7-year-old Girl.

PMID- 24449426
TI  - Intrapartum acquired skull fracture as first sign of Menkes disease.

PMID- 24449427
TI  - High vitamin D and calcium intakes reduce diet-induced obesity in mice by
      increasing adipose tissue apoptosis.
AB  - SCOPE: Modulation of apoptosis is emerging as a promising antiobesity strategy
      because removal of adipocytes through this process will result in reducing body
      fat. Effects of vitamin D on apoptosis are mediated via multiple signaling
      pathways that involve common regulators and effectors converging on cellular
      Ca(2+) . We have previously shown that 1,25-dihydroxyvitamin D3 induces the
      Ca(2+) signal associated with activation of Ca(2+) -dependent apoptotic proteases
      in mature adipocytes. In this study, a diet-induced obesity (DIO) mouse model was
      used to evaluate the role of vitamin D and calcium in adiposity. METHODS AND
      RESULTS: DIO mice fed high vitamin D3 , high Ca, and high D3 plus high Ca diets
      demonstrated a decreased body and fat weight gain, improved markers of adiposity
      and vitamin D status (plasma concentrations of glucose, insulin, adiponectin, 25
      hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone (PTH)), but an
      increased plasma Ca(2+) . High D3 and Ca intakes were associated with induction
      of apoptosis and activation of Ca(2+) -dependent apoptotic proteases, calpain and
      caspase-12, in adipose tissue of DIO mice. The combination of D3 plus Ca was more
      effective than D3 or Ca alone in decreasing adiposity. CONCLUSION: The results
      imply that high vitamin D and Ca intakes activate the Ca(2+) -mediated apoptotic
      pathway in adipose tissue. Targeting this pathway with vitamin D and Ca
      supplementation could contribute to the prevention and treatment of obesity.
      However, this potentially effective and affordable approach needs to be evaluated
      from a safety point of view.

PMID- 24449428
TI  - Systems biology for hepatologists.
AB  - Medicine is expected to benefit from combining usual cellular and molecular
      studies with high-throughput methods (genomics, transcriptomics, proteomics, and
      metabolomics). These methods, collectively known as omics, permit the
      determination of thousands of molecules (variations within genes, RNAs, proteins,
      metabolites) within a tissue, cell, or biological fluid. The use of these methods
      is very demanding in terms of the design of the study, acquisition, storage,
      analysis, and interpretation of the data. When carried out properly, these
      studies can reveal new etiological pathways, help to identify patients at risk
      for disease, and predict the response to specific treatments. Here we review
      these omics methods and mention several applications in hepatology research.

PMID- 24449429
TI  - Informal home care for elderly in Belgium: a study on the features and challenges
      of informal care at local level.
AB  - In Belgium, and in other OECD countries, there is a growing awareness about the
      importance of informal home care for the elderly's well-being. Informal care is
      considered as an intrinsically valuable social phenomenon. Public authorities in
      Belgium have been advocating an active policy of support for informal carers. In
      2007, an extensive survey was carried out in the Belgian municipality of Kruibeke
      in order to establish a better picture of the various needs of the elderly in
      their home situation, but also to better understand the way in which informal
      care is provided and perceived by care receivers and care givers. The study
      points to the need for support for the difficult burden of informal care and
      highlights the need for a coordinated and integrated approach to elderly care. 

PMID- 24449430
TI  - Screening for depression and high utilization of health care resources among
      patients in primary care.
AB  - The study aims to evaluate the prevalence of depression and the severity of
      depressive symptoms among primary care patients, who are high utilizers (HU) of
      health care resources. A cross-sectional, two-stage design was applied to screen
      for depression using the Brief Psychiatric Health Questionnaire and the
      Diagnostic Expert System for Psychiatric Disorders. A total of 38 primary care
      physicians accredited to practice in Berlin and Potsdam in Germany participated
      in the study. A total of 1,775 patients participated, 507 were identified as HU,
      182 (36%) of these were depressed compared to 81 (11%) of the typical utilizers
      (p < 0.001). The depression score was higher and acute suicidality was more
      prevalent in HU than in typical utilizers (p < 0.001). Our results suggest that
      HU represent a population with a high prevalence of depression in primary care
      and should be considered for routine depression screening.

PMID- 24449431
TI  - Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase)
      gene are responsible for a neurobehavioral deficit in two pediatric unrelated
      patients.
AB  - Inactivating mutations in the BCKDK gene, which codes for the kinase responsible
      for the negative regulation of the branched-chain alpha-keto acid dehydrogenase
      complex (BCKD), have recently been associated with a form of autism in three
      families. In this work, two novel exonic BCKDK mutations, c.520C>G/p.R174G and
      c.1166T>C/p.L389P, were identified at the homozygous state in two unrelated
      children with persistently reduced body fluid levels of branched-chain amino
      acids (BCAAs), developmental delay, microcephaly, and neurobehavioral
      abnormalities. Functional analysis of the mutations confirmed the missense
      character of the c.1166T>C change and showed a splicing defect
      r.[520c>g;521_543del]/p.R174Gfs1*, for c.520C>G due to the presence of a new
      donor splice site. Mutation p.L389P showed total loss of kinase activity.
      Moreover, patient-derived fibroblasts showed undetectable (p.R174Gfs1*) or barely
      detectable (p.L389P) levels of BCKDK protein and its phosphorylated substrate
      (phospho-E1alpha), resulting in increased BCKD activity and the very rapid BCAA
      catabolism manifested by the patients' clinical phenotype. Based on these
      results, a protein-rich diet plus oral BCAA supplementation was implemented in
      the patient homozygous for p.R174Gfs1*. This treatment normalized plasma BCAA
      levels and improved growth, developmental and behavioral variables. Our results
      demonstrate that BCKDK mutations can result in neurobehavioral deficits in humans
      and support the rationale for dietary intervention. 

PMID- 24449432
TI  - Methods for Performing Survival Curve Quality-of-Life Assessments.
AB  - BACKGROUND: Many medical decisions involve an implied choice between alternative
      survival curves, typically with differing quality of life. Common preference
      assessment methods neglect this structure, creating some risk of distortions.
      METHODS: Survival curve quality-of-life assessments (SQLA) were developed from
      Gompertz survival curves fitting the general population's survival. An algorithm
      was developed to generate relative discount rate-utility (DRU) functions from a
      standard survival curve and health state and an equally attractive alternative
      curve and state. A least means squared distance algorithm was developed to
      describe how nearly 3 or more DRU functions intersect. These techniques were
      implemented in a program called X-Trade and tested. RESULTS: SQLA scenarios can
      portray realistic treatment choices. A side effect scenario portrays one
      prototypical choice, to extend life while experiencing some loss, such as an
      amputation. A risky treatment scenario portrays procedures with an initial
      mortality risk. A time trade scenario mimics conventional time tradeoffs. Each
      SQLA scenario yields DRU functions with distinctive shapes, such as sigmoid
      curves or vertical lines. One SQLA can imply a discount rate or utility if the
      other value is known and both values are temporally stable. Two SQLA exercises
      imply a unique discount rate and utility if the inferred DRU functions intersect.
      Three or more SQLA results can quantify uncertainty or inconsistency in discount
      rate and utility estimates. Pilot studies suggested that many subjects could
      learn to interpret survival curves and do SQLA. LIMITATIONS: SQLA confuse some
      people. Compared with SQLA, standard gambles quantify very low utilities more
      easily, and time tradeoffs are simpler for high utilities. When discount rates
      approach zero, time tradeoffs are as informative and easier to do than SQLA.
      CONCLUSIONS: SQLA may complement conventional utility assessment methods.

PMID- 24449433
TI  - Adjusting survival time estimates to account for treatment switching in
      randomized controlled trials--an economic evaluation context: methods,
      limitations, and recommendations.
AB  - BACKGROUND: Treatment switching commonly occurs in clinical trials of novel
      interventions in the advanced or metastatic cancer setting. However, methods to
      adjust for switching have been used inconsistently and potentially
      inappropriately in health technology assessments (HTAs). OBJECTIVE: We present
      recommendations on the use of methods to adjust survival estimates in the
      presence of treatment switching in the context of economic evaluations. METHODS:
      We provide background on the treatment switching issue and summarize methods used
      to adjust for it in HTAs. We discuss the assumptions and limitations associated
      with adjustment methods and draw on results of a simulation study to make
      recommendations on their use. RESULTS: We demonstrate that methods used to adjust
      for treatment switching have important limitations and often produce bias in
      realistic scenarios. We present an analysis framework that aims to increase the
      probability that suitable adjustment methods can be identified on a case-by-case
      basis. We recommend that the characteristics of clinical trials, and the
      treatment switching mechanism observed within them, should be considered
      alongside the key assumptions of the adjustment methods. Key assumptions include
      the "no unmeasured confounders" assumption associated with the inverse
      probability of censoring weights (IPCW) method and the "common treatment effect"
      assumption associated with the rank preserving structural failure time model
      (RPSFTM). CONCLUSIONS: The limitations associated with switching adjustment
      methods such as the RPSFTM and IPCW mean that they are appropriate in different
      scenarios. In some scenarios, both methods may be prone to bias; "2-stage"
      methods should be considered, and intention-to-treat analyses may sometimes
      produce the least bias. The data requirements of adjustment methods also have
      important implications for clinical trialists.

PMID- 24449434
TI  - Strategies for efficient computation of the expected value of partial perfect
      information.
AB  - Expected value of information methods evaluate the potential health benefits that
      can be obtained from conducting new research to reduce uncertainty in the
      parameters of a cost-effectiveness analysis model, hence reducing decision
      uncertainty. Expected value of partial perfect information (EVPPI) provides an
      upper limit to the health gains that can be obtained from conducting a new study
      on a subset of parameters in the cost-effectiveness analysis and can therefore be
      used as a sensitivity analysis to identify parameters that most contribute to
      decision uncertainty and to help guide decisions around which types of study are
      of most value to prioritize for funding. A common general approach is to use
      nested Monte Carlo simulation to obtain an estimate of EVPPI. This approach is
      computationally intensive, can lead to significant sampling bias if an inadequate
      number of inner samples are obtained, and incorrect results can be obtained if
      correlations between parameters are not dealt with appropriately. In this
      article, we set out a range of methods for estimating EVPPI that avoid the need
      for nested simulation: reparameterization of the net benefit function, Taylor
      series approximations, and restricted cubic spline estimation of conditional
      expectations. For each method, we set out the generalized functional form that
      net benefit must take for the method to be valid. By specifying this functional
      form, our methods are able to focus on components of the model in which
      approximation is required, avoiding the complexities involved in developing
      statistical approximations for the model as a whole. Our methods also allow for
      any correlations that might exist between model parameters. We illustrate the
      methods using an example of fluid resuscitation in African children with severe
      malaria.

PMID- 24449435
TI  - iTRAQ as a method for optimization: enhancing peptide recovery after gel
      fractionation.
AB  - At the dawn of a new era in label-free quantitation on high-resolution MS
      instruments, classical methods such as iTRAQ continue to provide very useful
      insights in comparative proteomics. The potential to multiplex samples makes this
      reporter-based labeling technique highly suited for method optimization as
      demonstrated here by a set of standard series. Instead of studying ratios of
      annotated proteins, we propose an alternative method, based on the analysis of
      the average reporter ratios of all the spectra from a sample or a large distinct
      subset herein. This strategy circumvents the bias, associated with the annotation
      and iTRAQ quantitation, leading to increased adequacy in measuring yield
      differences between workflows. As gel electrophoresis prior to MS analysis is
      highly beneficial, for example, as a fractionation step, the approach was applied
      to evaluate the influence of several parameters of the established in-gel
      digestion protocol. We quantified the negative effect of SYPRO Ruby staining and
      the positive effect of gel fixation prior to digestion on peptide yield. Finally,
      we emphasize the benefits of adding CaCl2 and ACN to a tryptic in-gel digest,
      resulting in an up to tenfold enhanced peptide recovery and fewer trypsin missed
      cleavages. 

PMID- 24449436
TI  - Probing bacterial uptake of glycosylated ciprofloxacin conjugates.
AB  - Mono- and disaccharide-functionalised conjugates of the fluoroquinolone
      antibiotic ciprofloxacin have been synthesised and used as chemical probes of the
      bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities
      against a panel of clinically relevant bacteria were determined: the ability of
      these conjugates to inhibit their target DNA gyrase and to be transported into
      the bacteria was assessed by using in vivo and in vitro assays. The data suggest
      a lack of active uptake through sugar transporters and that although the addition
      of monosaccharides is compatible with the inhibition of DNA gyrase, the addition
      of a disaccharide results in a significant decrease in antimicrobial activity.

PMID- 24449437
TI  - AgI microplate monocrystals with polar {0001} facets: spontaneous photocarrier
      separation and enhanced photocatalytic activity.
AB  - Elucidating the facet-dependent photocatalytic activity of semiconductor
      photocatalysts is important in improving the overall efficiency of
      photocatalysis. Furthermore, combining facet control with selective deposition of
      oxidation and/or reduction cocatalysts on specific faces of semiconductor
      photocatalysts is potentially an effective strategy to synergistically optimize
      the functionality of photocatalysts. In the present study, high-purity wurtzite
      type beta-AgI platelet microcrystals with polar {0001} facets were prepared by a
      facile polyvinylpyrrolidone-assisted precipitation reaction. The polar-faceted
      AgI microplates were used as archetypes to demonstrate preferential diametric
      migration (i.e., effective separation) of photogenerated electrons and holes
      along the c axis. Such vectorial electron-hole separation stems from the
      asymmetric surface structures, which give rise to distinct photoexcited reaction
      behaviors on the +/-(0001) polar facets of wurtzite-type semiconductors.
      Furthermore, on selective deposition of Ag and MnOx (1.5<x<2) cocatalysts on the
      reductive (0001) and oxidative (0001) facets, respectively, photocatalytic
      activity of the AgI microplates in degrading organic pollutants was dramatically
      enhanced thanks to the broad light-absorption range, strong dye-adsorption
      ability, and effective spatial separation of photocarriers.

PMID- 24449438
TI  - Nano-engineered erythrocyte ghosts as inhalational carriers for delivery of
      fasudil: preparation and characterization.
AB  - PURPOSE: Nanoerythrosomes (NERs), an engineered derivative of erythrocytes, have
      long been used as drug delivery carriers. These cell based carriers are
      biocompatible and biodegradable, and they exhibit efficient drug loading,
      targeting specificity and prolonged biological half-life. In this study, we have
      evaluated the feasibility of NERs as inhalable carriers for delivery of fasudil,
      an investigational drug for the treatment of pulmonary arterial hypertension.
      METHODS: We prepared NERs by hypotonic lysis of erythrocytes derived from rat
      blood followed by extrusion through polycarbonate membranes. The formulations
      were optimized and characterized for size, morphology, entrapment efficiency,
      stability, cellular uptake and in-vitro release profiles followed by monitoring
      of drug absorption and safety evaluation after intratracheal administration of
      fasudil-loaded NERs into rats. RESULTS: NERs were spherical in shape with an
      average size of 154.1 +/- 1.31 nm and the drug loading efficiency was 48.76 +/-
      2.18%. Formulations were stable when stored at 4 degrees C for 3 weeks. When
      incubated with rat pulmonary arterial smooth muscle cells (PASM), a significant
      amount of NERs was taken up by PASM cells. The drug encapsulated in NERs
      inhibited the rho-kinase activity upto 50%, which was comparable with the plain
      fasudil. A ~6-8 fold increase in the half-life of fasudil was observed when
      encapsulated in NERs. CONCLUSION: This study suggests that nanoerythrosomes can
      be used as cell derived carriers for inhalational delivery of fasudil.

PMID- 24449439
TI  - A novel formulation based on 2,3-di(tetradecyloxy)propan-1-amine cationic lipid
      combined with polysorbate 80 for efficient gene delivery to the retina.
AB  - PURPOSE: The aim of the present study was to evaluate the potential application
      of a novel formulation based on a synthesized cationic lipid 2,3
      di(tetradecyloxy)propan-1-amine, combined with polysorbate 80 to deliver the pCMS
      EGFP plasmid into the rat retina. METHODS: We elaborated lipoplexes by mixing the
      formulation containing the cationic lipid and the polysorbate 80 with the plasmid
      at different cationic lipid/DNA ratios (w/w). Resulted lipoplexes were
      characterized in terms of size, charge, and capacity to condense, protect and
      release the DNA. In vitro transfection studies were performed in HEK-293 and ARPE
      19 cells. Formulations were also tested in vivo by monitoring the expression of
      the EGFP after intravitreal and subretinal injections in rat eyes. RESULTS: At
      2/1 cationic lipid/DNA mass ratio, the resulted lipoplexes had 200 nm of
      hydrodynamic diameter; were positive charged, spherical, protected DNA against
      enzymatic digestion and transfected efficiently HEK-293 and ARPE-19 cultured
      cells exhibiting lower cytotoxicity than LipofectamineTM 2000. Subretinal
      administrations transfected mainly photoreceptors and retinal pigment epithelial
      cells; whereas intravitreal injections produced a more uniform distribution of
      transfection through the inner part of the retina. CONCLUSIONS: These results
      hold great expectations for other gene delivery formulations based on this
      cationic lipid for retinal gene therapy purposes.

PMID- 24449440
TI  - Arachidonic acid-modified lovastatin discoidal reconstituted high density
      lipoprotein markedly decreases the drug leakage during the remodeling behaviors
      induced by lecithin cholesterol acyltransferase.
AB  - PURPOSE: Our previous studies indicated that drug leaked from discoidal
      reconstituted high density lipoprotein (d-rHDL) during the remodeling behaviors
      induced by lecithin cholesterol acyl transferase (LCAT) abundant in circulation,
      thus decreasing the drug amount delivered into the target. In this study,
      arachidonic acid (AA)-modified d-rHDL loaded with lovastatin (LT) were engineered
      as AA-LT-d-rHDL to explore whether AA modification could reduce the drug leakage
      during the remodeling behaviors induced by LCAT and further deliver more drug
      into target cells to improve efficacy. METHODS: After successful preparation of
      AA-LT-d-rHDL with different AA modification amount, a series of in vitro
      remodeling behaviors were investigated. Furthermore, inhibition on macrophage
      derived foam cell formation was chosen to evaluate drug efficacy of AA-LT-d-rHDL.
      RESULTS: In vitro physicochemical characterizations studies showed that all LT-d
      rHDL and AA-LT-d-rHDL preparations had nano-size, negative surface charge, high
      entrapment efficiency (EE) and comparable drug loading efficiency (DL). With
      increment of AA modification amount, AA-LT-d-rHDL manifested lower reactivity
      with LCAT, thus significantly reducing the undesired drug leakage during the
      remodeling behaviors induced by LCAT, eventually exerting stronger efficacy on
      inhibition of macrophage-derived foam cell formation. CONCLUSION: AA-LT-d-rHDL
      could decrease the drug leakage during the remodeling behaviors induced by LCAT
      and fulfill efficient drug delivery.

PMID- 24449441
TI  - Direct microneedle array fabrication off a photomask to deliver collagen through
      skin.
AB  - PURPOSE: To fabricate microneedle arrays directly off a photomask using a simple
      photolithographical approach and evaluate their potential for delivering
      collagen. METHODS: A simple photolithographical approach was developed by using
      photomask consisting of embedded micro-lenses that govern microneedle geometry in
      a mould free process. Microneedle length was controlled by use of simple glass
      scaffolds as well as addition of backing layer. The fabricated arrays were tested
      for their mechanical properties by using a force gauge as well as insertion into
      human skin with trypan blue staining. Microneedle arrays were then evaluated for
      the delivery of fluorescent collagen, which was evaluated using a confocal laser
      scanning microscope. RESULTS: Microneedles with sharp tips ranging between 41.5
      +/- 8.4 MUm and 71.6 +/- 13.7 MUm as well as of two different lengths of 1336 +/-
      193 MUm and 957 +/- 171 MUm were fabricated by using the photomasks. The
      microneedles were robust and resisted fracture forces up to 25 N. They were also
      shown to penetrate cadaver human skin samples with ease; especially microneedle
      arrays with shorter length of 957 MUm penetrated up to 72% of needles. The
      needles were shown to enhance permeation of collagen through cadaver rat skin, as
      compared to passive diffusion of collagen. CONCLUSIONS: A simple and mould free
      approach of fabricating polymeric microneedle array is proposed. The fabricated
      microneedle arrays enhance collagen permeation through skin.

PMID- 24449442
TI  - Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after
      vaginal delivery in mice.
AB  - PURPOSE: To assess the potential of polymeric nanoparticles (NPs) to affect the
      genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV
      microbicide drug candidate dapivirine after vaginal delivery. METHODS: Dapivirine
      loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were
      prepared by a nanoprecipitation method. Genital distribution of NPs and their
      ability to modify the PK of dapivirine up to 24 h was assessed after vaginal
      instillation in a female mouse model. Also, the safety of NPs upon daily
      administration for 14 days was assessed by histological analysis and
      chemokine/cytokine content in vaginal lavages. RESULTS: PEO-PCL NPs (180-200 nm)
      were rapidly eliminated after administration but able to distribute throughout
      the vagina and lower uterus, and capable of tackling mucus and penetrate the
      epithelial lining. Nanocarriers modified the PK of dapivirine, with higher drug
      levels being recovered from vaginal lavages and vaginal/lower uterine tissues as
      compared to a drug suspension. Systemic drug exposure was reduced when NPs were
      used. Also, NPs were shown safe upon administration for 14 days. CONCLUSIONS:
      Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable genital drug
      levels, thus attesting the potential value of using this vaginal drug delivery
      nanosystem in the context of HIV prophylaxis.

PMID- 24449443
TI  - Saturated long-chain esters of isopulegol as novel permeation enhancers for
      transdermal drug delivery.
AB  - PURPOSE: Saturated long-chain esters of isopulegol were synthesized and their
      activities as permeation enhancers for transdermal delivery of amlodipine and
      flurbiprofen were investigated, in contrast to the saturated fatty acids and
      isopulegol, as well as their physical mixtures. METHODS: In vitro permeation
      experiments, confocal laser scanning microscopy (CLSM) and attenuated total
      reflection Fourier transform infrared (ATR-FTIR) spectroscopy were introduced to
      investigate the regulation of enhancers in the skin permeability and biophysical
      properties. With in vitro cytotoxicity test and in vivo erythema model, the skin
      irritation of enhancers was evaluated. RESULTS: The esters significantly
      increased the permeation of amlodipine and flurbiprofen, whereas saturated fatty
      acids and isopulegol had no such effect and even decreased the drug permeation
      when they were used alone or in combination. These results were supported by CLSM
      and ATR-FTIR studies, which revealed that only the esters could decrease the
      order of the alkyl chains in the skin lipids. Additionally, almost no skin
      irritation and cytotoxicity were observed for these esters. CONCLUSIONS:
      Saturated long-chain esters of isopulegol are shown to be suitable permeation
      enhancers for transdermal drug delivery. Covalent attachment of isopulegol and
      saturated fatty acids might represent a promising strategy to design novel and
      potent permeation enhancers.

PMID- 24449444
TI  - An antimicrobial role for zinc in innate immune defense against group A
      streptococcus.
AB  - BACKGROUND: Zinc plays an important role in human immunity, and it is known that
      zinc deficiency in the host is linked to increased susceptibility to bacterial
      infection. In this study, we investigate the role of zinc efflux in the
      pathogenesis of Streptococcus pyogenes (group A Streptococcus [GAS]), a human
      pathogen responsible for superficial infections, such as pharyngitis and
      impetigo, and severe invasive infections. METHODS: The clinically important M1T1
      wild-type strain was used in this study, and isogenic mutants were constructed
      with deletions in the czcD gene (Spy0653; which encodes a putative zinc efflux
      pump) and adjacent gczA gene (Spy0654; which encodes a putative zinc-dependent
      activator of czcD). Wild-type, isogenic mutants and complemented strains were
      tested for resistance against zinc stress, intracellular zinc accumulation, and
      virulence. RESULTS: Both czcD and gczA mutants exhibited increased sensitivity to
      zinc. Transcriptional analyses indicate that GczA upregulates czcD in response to
      zinc. Both mutants displayed increased susceptibility to human neutrophil killing
      and reduced virulence in a murine infection model. Furthermore, we showed that
      neutrophils mobilize zinc in response to GAS. CONCLUSIONS: These data indicate
      that the innate immune system may use zinc as an antimicrobial agent and that
      zinc efflux is an important contributor to GAS pathogenesis.

PMID- 24449445
TI  - Significance of zinc in innate immune defense against Streptococcus pyogenes.

PMID- 24449446
TI  - Evaluation of the repellent effects of Nepeta parnassica extract, essential oil,
      and its major nepetalactone metabolite against mosquitoes.
AB  - The dichloromethane-methanol extract, the essential oil obtained by
      hydrodistillation from Nepeta parnassica, and the isolated 4aalpha,7alpha,7abeta
      nepetalactone were evaluated for their repellent effect against the mosquitoes
      Aedes (Stegomyia) cretinus Edwards and Culex pipiens pipiens biotype molestus
      Forskal. The chemical analysis of N. parnassica essential oil, dominated by
      oxygenated monoterpenes (87 %), revealed 4aalpha,7alpha,7abeta-nepetalactone
      (36.8%), 1,8-cineole (25.5%), and 4aalpha,7beta,7abeta-nepetalactone (11.1%) as
      the major constituents. The results of the insect bioassays showed that the
      essential oil and the dichloromethane-methanol extract of N. parnassica were very
      active against Aedes cretinus for up to 3 h and against Culex pipiens for up to 2
      h post application. The isolated 4aalpha,7alpha,7abeta-nepetalactone showed very
      high mosquito repellency for periods of at least 2 h against both species.

PMID- 24449447
TI  - Comparative transcript expression analysis of miltefosine-sensitive and
      miltefosine-resistant Leishmania donovani.
AB  - Leishmania donovani is the causative agent of anthroponotic visceral
      leishmaniasis in the Indian subcontinent. Oral miltefosine therapy has recently
      replaced antimonials in endemic areas. However, the drug is at risk of emergence
      of resistance due to unrestricted use, and, already, there are indications
      towards decline in treatment efficacy. Hence, understanding the mechanism of
      miltefosine resistance in the parasite is crucial. We employed genomic microarray
      analysis to compare the gene expression patterns of miltefosine-resistant and
      miltefosine-sensitive L. donovani. Three hundred eleven genes, representing ~3.9%
      of the total Leishmania genome, belonging to various functional categories
      including metabolic pathways, transporters, and cellular components, were
      differentially expressed in miltefosine-resistant parasite. Results in the
      present study highlighted the probable mechanisms by which the parasite sustains
      miltefosine pressure including (1) compromised DNA replication/repair mechanism,
      (2) reduced protein synthesis and degradation, (3) altered energy utilization via
      increased lipid degradation, (4) increased ABC 1-mediated drug efflux, and (5)
      increased antioxidant defense mechanism via elevated trypanothione metabolism.
      The study provided the comprehensive insight into the underlying mechanism of
      miltefosine resistance in L. donovani that may be useful to design strategies to
      increase lifespan of this important oral antileishmanial drug.

PMID- 24449448
TI  - Biochemical and molecular characterization of the tegument protein RT10 from
      Raillietina tetragona.
AB  - Tegument antigens of tapeworm play an important role in modulation of host
      response and parasite survival. Characterizing appropriate antigens for parasite
      infection diagnosis and vaccination is rational and could have both economic and
      epidemiological significance in poultry industry. In the present study, a major
      protoscolex homologue (named RT10) of Echinococcus and Taenia spp. was amplified
      from Raillietina tetragona cestode. The RT10 cDNA was 1,877 bp long containing an
      open reading frame of 1,683 bp nucleotides, which encoded a deduced protein of
      560 amino acids with an isoelectric point of 6.33. Secondary structure analysis
      demonstrated that RT10 was both hydrophilic and antigenic, and possessed N
      terminal FERM domain and C-terminal ERM domain, respectively. With the same
      structural properties of previously reported antigens from Echinococcus and
      Taenia spp., RT10 tegument antigen had a more than 82% similarity in nucleotide
      level with initially reported antigens from Echinococcus and Taenia spp., and a
      more than 83% similarity in protein level, with the highest similarity of 85.2%
      to Taenia antigen H17g. In addition, phylogenetic analysis illustrated a high
      consistency between different genus antigens and evolutionary branching. Although
      the detailed function of RT10 is still unknown, the high sequence conservation
      and structural similarity to formerly identified tegument antigens from
      Echinococcus and Taenia spp. suggested that RT10 may play a similar role as the
      previous reported antigens between cestode and host. It is significant to clarify
      the antigenic and serodiagnostic characteristics in the subsequent work.

PMID- 24449449
TI  - Isolation and characterization of Acanthamoeba strains from soil samples in Gran
      Canaria, Canary Islands, Spain.
AB  - Free-living Amoebae of Acanthamoeba genus include non-pathogenic and pathogenic
      strains that are currently classified in 18 different genotypes, T1-T18. In this
      study, a survey was carried out to evaluate the presence of Acanthamoeba strains
      in soil samples collected between 2012 and 2013 in Gran Canaria Island, Canary
      Islands, Spain. Samples were inoculated onto non-nutrient agar (NNA) plates and
      were checked for the presence of Acanthamoeba. Identification of Acanthamoeba
      strains was based on the morphology of the cyst and trophozoite forms.
      Subsequently, positive samples were cloned for their molecular characterization
      at the genotype level by sequencing the DF3 region located in the 18S rDNA gene
      of Acanthamoeba as previously described. Sequencing results revealed the presence
      of T2, T5 and T4 genotypes within the studied samples. To the best of our
      knowledge, this is the first report demonstrating the presence of Acanthamoeba in
      Gran Canaria Island and the first study at the genotype level in the Canary
      Islands. 

PMID- 24449451
TI  - Improvement of constraint-based flux estimation during L-phenylalanine production
      with Escherichia coli using targeted knock-out mutants.
AB  - Fed-batch production of the aromatic amino acid L-phenylalanine was studied with
      recombinant Escherichia coli strains on a 15 L-scale using glycerol as carbon
      source. Flux Variability Analysis (FVA) was applied for intracellular flux
      estimation to obtain an insight into intracellular flux distribution during L
      phenylalanine production. Variability analysis revealed great flux uncertainties
      in the central carbon metabolism, especially concerning malate consumption. Due
      to these results two recombinant strains were genetically engineered differing in
      the ability of malate degradation and anaplerotic reactions (E. coli FUS4.11
      DeltamaeA pF81kan and E. coli FUS4.11 DeltamaeA DeltamaeB pF81kan). Applying
      these malic enzyme knock-out mutants in the standardized L-phenylalanine
      production process resulted in almost identical process performances (e.g., L
      phenylalanine concentration, production rate and byproduct formation). This
      clearly highlighted great redundancies in central metabolism in E. coli.
      Uncertainties of intracellular flux estimations by constraint-based analyses
      during fed-batch production of L-phenylalanine were drastically reduced by
      application of the malic enzyme knock-out mutants.

PMID- 24449452
TI  - Endoscopy outreach and upper gastrointestinal bleed: an audit.

PMID- 24449454
TI  - Enantioselective surface plasmon resonance sensor based on C60 fullerene
      glutathione self-assembled monolayer (SAM).
AB  - A novel enantioselective surface plasmon resonance (SPR) sensor based on a self
      assembled monolayer of C60 fullerene as the chiral selector is proposed. A
      binding assay, apparent affinity constant, and apparent dissociation binding
      constant were used to analyze and study the enantioselectivity of C60 fullerene
      glutathione film for L-histidine, which was chosen as the model analyte. The
      apparent affinity constant for the complex formed by L-histidine with C60
      fullerene-glutathione film was 5.2 x 10(9)  M(-1). The proposed SPR sensor can be
      used for the assay of L-histidine in the 10(-10)-10(-7)  mol/L concentration
      range.

PMID- 24449455
TI  - Reply: To PMID 24037773.

PMID- 24449456
TI  - Japanese plums (Prunus salicina Lindl.) and phytochemicals--breeding,
      horticultural practice, postharvest storage, processing and bioactivity.
AB  - Previous reviews of plum phytochemical content and health benefits have
      concentrated on the European plum, Prunus domestica L. However, the potential
      bioactivity of red- and dark red-fleshed Japanese plums, Prunus salicina Lindl.,
      so-called blood plums, appears to warrant a significant increase in exposure, as
      indicated in a recent review of the whole Prunus genus. Furthermore, Japanese
      plums are the predominant plum produced on an international basis. In this review
      the nutrient and phytochemical content, breeding, horticultural practice,
      postharvest treatment and processing as well as bioactivity (emphasising in vivo
      studies) of Japanese plum are considered, with a focus on the anthocyanin content
      that distinguishes the blood plums.

PMID- 24449457
TI  - A general route to hollow mesoporous rare-earth silicate nanospheres as a
      catalyst support.
AB  - Hollow mesoporous structures have recently aroused intense research interest
      owing to their unique structural features. Herein, an effective and precisely
      controlled synthesis of hollow rare-earth silicate spheres with mesoporous shells
      is reported for the first time, produced by a simple hydrothermal method, using
      silica spheres as the silica precursors. The as-prepared hollow rare-earth
      silicate spheres have large specific surface area, high pore volume, and
      controllable structure parameters. The results demonstrate that the selection of
      the chelating reagent plays critical roles in forming the hollow mesoporous
      structures. In addition, a simple and low-energy-consuming approach to synthesize
      highly stable and dispersive gold nanoparticle-yttrium silicate (AuNPs/YSiO)
      hollow nanocomposites has also been developed. The reduction of 4-nitrophenol
      with AuNPs/YSiO hollow nanocomposites as the catalyst has clearly demonstrated
      that the hollow rare-earth silicate spheres are good carriers for Au
      nanoparticles. This strategy can be extended as a general approach to prepare
      multifunctional yolk-shell structures with diverse compositions and morphologies
      simply by replacing silica spheres with silica-coated nanocomposites. 

PMID- 24449458
TI  - Concise review: Bone marrow-derived mesenchymal stem cells change phenotype
      following in vitro culture: implications for basic research and the clinic.
AB  - Mesenchymal stem cells (MSCs) are increasingly being used in tissue engineering
      and cell-based therapies in all fields ranging from orthopedic to cardiovascular
      medicine. Despite years of research and numerous clinical trials, MSC therapies
      are still very much in development and not considered mainstream treatments. The
      majority of approaches rely on an in vitro cell expansion phase in monolayer to
      produce large cell numbers prior to implantation. It is clear from the literature
      that this in vitro expansion phase causes dramatic changes in MSC phenotype which
      has very significant implications for the development of effective therapies.
      Previous reviews have sought to better characterize these cells in their native
      and in vitro environments, described known stem cell interactions within the bone
      marrow, and discussed the use of innovative culture systems aiming to model the
      bone marrow stem cell niche. The purpose of this review is to provide an update
      on our knowledge of MSCs in their native environment, focusing on bone marrow
      derived MSCs. We provide a detailed description of the differences between naive
      cells and those that have been cultured in vitro and examine the effect of
      isolation and culture parameters on these phenotypic changes. We explore the
      concept of "one step" MSC therapy and discuss the potential cellular and clinical
      benefits. Finally, we describe recent work attempting to model the MSC bone
      marrow niche, with focus on both basic research and clinical applications and
      consider the challenges associated with these new generation culture systems.

PMID- 24449460
TI  - iRehab in aphasia treatment.

PMID- 24449461
TI  - Using mobile technology with individuals with aphasia: native iPad features and
      everyday apps.
AB  - The use of mobile technology, including smartphones and tablet devices, is a
      growing trend among adults nationwide, and its potential use in aphasia
      rehabilitation has generated widespread interest. Despite this trend, adults
      living with disability are less likely than other adults to go online.
      Complicating things further, most adults living with aphasia come from a
      generation where computers and technology were not an integral part of their
      lives. Additionally, training adults with aphasia requires a different approach
      than training those in the same age bracket without a disability. This article
      describes the mobile technology program at the Adler Aphasia Center in Maywood,
      New Jersey. The goal of this program is to improve access to mobile technology
      for people with aphasia. The use of mobile devices is the focus of the article.
      Mobile technology concepts and skills needed to establish a strong foundation for
      successful iPad (Apple Inc., Cupertino, CA) use are suggested. We discuss how
      apps may be used to support aphasia therapy with a focus on apps that are native
      to the iPad and on other apps that were not specifically developed for aphasia
      rehabilitation. Challenges in implementing a mobile technology program for people
      with aphasia and individual member success stories are included. 

PMID- 24449462
TI  - Best practices for incorporating non-aphasia-specific apps into therapy.
AB  - Given the proliferation of tablets and smartphones, there is a rising desire to
      use these technologies and apps in clinical practice. This article offers best
      practice guidelines for integrating apps into aphasia rehabilitation. In concert
      with evidence-based practice guidelines, it describes the steps for deciding
      which apps to consider and how to judge their appropriateness. We recommend a
      process for selecting apps that involves three stages. The first step is no
      different than that used in traditional treatment planning. It involves assessing
      the client's speech and language, selecting the focus of treatment, and
      identifying evidence-based approaches to addressing this focus. When technology
      is being considered, however, it is also necessary to assess sensory, motor, and
      cognitive requirements of the apps and hardware being considered, as well as the
      client's ability to operate this technology. Finally, the clinician must consider
      hardware and Internet demands of the app and whether these are accessible to the
      client. We illustrate the process through a description of three cases for which
      we used apps that were not specifically designed for aphasia to deliver evidence
      based treatments. 

PMID- 24449463
TI  - Integrating the iPad into an intensive, comprehensive aphasia program.
AB  - The proliferation of tablet technology and the development of apps to support
      aphasia rehabilitation offer increasing opportunities for speech-language
      pathologists in a clinical setting. This article describes the components of an
      Intensive Comprehensive Aphasia Program at Boston University and details how
      usage of the iPad (Apple Inc., Cupertino, CA) was incorporated. We describe how
      the iPad was customized for use in individual, dyadic, and group treatment
      formats and how its use was encouraged through home practice tasks. In addition
      to providing the participants with step-by-step instructions for the usage of
      each new app, participants had multiple opportunities for practice across various
      treatment formats. Examples of how the participants continued using their iPad
      beyond the program suggest how the usage of this device has generalized into
      their day-to-day life. An overall summary of performance on targeted linguistic
      measures as well as an analysis of functional and quality-of-life measures reveal
      statistically significant improvements pre- to posttreatment. 

PMID- 24449464
TI  - Development of an impairment-based individualized treatment workflow using an
      iPad-based software platform.
AB  - Individuals with language and cognitive deficits following brain damage likely
      require long-term rehabilitation. Consequently, it is a huge practical problem to
      provide the continued communication therapy that these individuals require. The
      present project describes the development of an impairment-based individualized
      treatment workflow using a software platform called Constant Therapy. This
      article is organized into two sections. We will first describe the general
      methods of the treatment workflow for patients involved in this study. There are
      four steps in this process: (1) the patient's impairment is assessed using
      standardized tests, (2) the patient is assigned a specific and individualized
      treatment plan, (3) the patient practices the therapy at home and at the clinic,
      and (4) the clinician and the patient can analyze the results of the patient's
      performance remotely and monitor and alter the treatment plan accordingly. The
      second section provides four case studies that provide a representative sample of
      participants progressing through their individualized treatment plan. The
      preliminary results of the patient treatment provide encouraging evidence for the
      feasibility of a rehabilitation program for individuals with brain damage based
      on the iPad (Apple Inc., Cupertino, CA). 

PMID- 24449465
TI  - iPractice: piloting the effectiveness of a tablet-based home practice program in
      aphasia treatment.
AB  - The current study investigated the effectiveness of a home practice program based
      on the iPad (Apple Inc., Cupertino, CA), implemented after 2 weeks of intensive
      language therapy, for maintaining and augmenting treatment gains in people with
      chronic poststroke aphasia. Five of eight original participants completed the 6
      month home practice program in which they autonomously practiced retrieving words
      for objects and actions. Half of these words had been trained and half were
      untrained during therapy. Practice included tasks such as naming to
      confrontation, repeating from a video model, and picture/word matching presented
      on an iPad. All participants maintained advances made on words trained during the
      intensive treatment and additionally were able to learn new words by practicing
      daily over a 6-month period. The iPad and other tablet devices have great
      potential for personalized home practice to maintain and augment traditional
      aphasia rehabilitation. It appears that motivation to use the technology and
      adequate training are more important factors than age, aphasia type or severity,
      or prior experience with computers. 

PMID- 24449466
TI  - alpha-1-antitrypsin inhibits acute liver failure in mice.
AB  - Acute liver failure remains a critical clinical condition, with high mortality
      rates, and increased apoptosis of hepatocytes represents a key event in the cause
      of liver failure. Alpha-1-antitrypsin (AAT) is synthesized and secreted mainly by
      hepatocytes, and plasma purified AAT is used for augmentation therapy in patients
      with AAT deficiency. Because AAT therapy exerts antiinflammatory and immune
      modulatory activities in various experimental models, and it was recently
      suggested that AAT exerts antiapoptotic activities, we aimed to explore whether
      administration of AAT may represent a therapeutic strategy to treat acute liver
      failure in mice. Well-established preclinical models of acute liver failure such
      as the Jo2 FAS/CD95 activating model and models of acetaminophen and alpha
      amanitin poisoning were used. Therapeutic effects of AAT were evaluated by
      monitoring animal survival, histopathological changes, measurement of caspase
      activity, and serum cytokine levels. Systemic treatment with AAT significantly
      decreased Jo2-induced liver cell apoptosis and prolonged survival of mice. Native
      and oxidized (lacking elastase inhibitory activity) forms of AAT were equally
      effective in preventing acute liver injury and showed direct inhibition of active
      caspase-3 and -8 in liver homogenates and in a cell-free system in vitro.
      Concomitantly, mice treated with AAT showed significantly lower serum levels of
      tumor necrosis factor alpha (TNF-alpha), which also paralleled the reduced
      activity of ADAM17 (TACE). Noticeably, the increased survival and a reduction of
      apoptotic hepatocytes were also observed in the alpha-amanitin and acetaminophen
      induced liver injury mouse models. CONCLUSION: Our data suggest that systemic
      administration of AAT can be a promising therapy to treat acute liver failure and
      clinical studies to explore this treatment in humans should be initiated.

PMID- 24449467
TI  - Lectin-dependent localization of cell surface sialic acid-binding lectin Siglec
      9.
AB  - Siglecs are immunoglobulin lectin group proteins that recognize the sialic acid
      moiety. We previously reported that the expression of Siglec-9 on the macrophage
      cell line RAW264 markedly enhanced Toll-like receptor (TLR)-induced interleukin
      (IL)-10 production and inhibited the production of proinflammatory cytokines. In
      this study, we examined the lectin-dependent anti-inflammatory activities of
      Siglec-9. IL-10 production was modestly reduced by a mutation that disrupted the
      lectin activity of Siglec-9, while the reduction in tumor necrosis factor-alpha
      was not affected. Membrane fractionation experiments revealed that a part of
      Siglec-9 resided in the detergent-insoluble microdomain, the so-called lipid raft
      fraction. The amount of Siglec-9 in the lipid raft fraction rapidly increased
      following TLR2 stimulation by peptidoglycan and peaked after 3-10 min. This time
      course was similar to that of TLR2. The double tyrosine mutant in immunoreceptor
      tyrosine-based inhibitory motifs moved to lipid rafts in a similar manner, while
      lectin-defective Siglec-9 was not detected in the lipid raft fraction. The
      production of IL-10 was partially reduced by cholesterol oxidase that disturbed
      lipid raft organization. Taken together, these results suggest that Siglecs
      exhibit lectin-dependent changes in cellular localization, which may be partly
      linked to its control mechanism that increases the production of IL-10. 

PMID- 24449468
TI  - Bringing an end to mandatory breast cancer screening in Uruguay.

PMID- 24449469
TI  - Redox-driven host-guest interactions allow the controlled release of captured
      cells on RGD-functionalized surfaces.
AB  - A quartz crystal microbalance technique with dissipation monitoring and a
      complementary optical microscopy technique were used for monitoring the capture
      and release of specific cells on a surface displaying a bifunctional molecular
      device, composed of a molecular scaffold endowed with the cell recognition
      property of an RGD ligand and a beta-CD/Fc redox-switchable system.

PMID- 24449470
TI  - Osteitis is a misnomer: a histopathology study in primary chronic rhinosinusitis.
AB  - BACKGROUND: The histological features of osteitis in chronic rhinosinusitis (CRS)
      in animal studies induced by bacterial inoculation into maxillary sinuses
      revealed inflammatory involvement of the underlying bone matrix and/or the
      Haversian system; however, human studies do not mention these findings. The
      objective of this study was to investigate the inflammatory characterization of
      osteitis in CRS. METHOD: A prospective study of primary CRS patients undergoing
      sinus surgery was conducted (August 2012 to April 2013). Bone-mucosa samples were
      taken from a predetermined site that correlated to a computed tomography
      location. Radiological bone thickness was measured. A blinded histopathological
      assessment included inflammatory infiltrate of bone, periosteal reaction,
      presence of osteoblasts or osteoclasts, fibrosis, and the percentage of new woven
      bone to total bone thickness, together with an overall opinion of whether neo
      osteogenesis was present. RESULTS: Twenty-two primary CRS patients (age 45.8 +/-
      15.6 years; 59.1% female) were recruited. CRS with polyps accounted for 59.1% of
      patients. The bony thickness measured radiologically was a median 1.72
      (interquartile range [IQR], 2.38; range, 0.3-12.14) mm. No samples (0%) had
      evidence of inflammatory infiltrate of bone; 90.9% had both osteoblasts present
      and new woven bone formation. Woven bone was greater with periosteal reaction
      (80.83% +/- 9.25% vs. 47.50% +/- 29.37%; p = 0.006), greater with osteoclasts
      present (80.00% +/- 12.58% vs 59.00% +/- 28.52%; p = 0.03), and greater when
      fibrosis was present (69.75% +/- 24.14% vs 25.00% +/- 7.07%; p = 0.003).
      CONCLUSION: Most primary CRS patients demonstrated evidence of new woven bone
      formation. True "osteitis" with inflammatory infiltrate of the bone was not
      observed. "Osteitis" is likely a process of neo-osteogenesis and bone remodeling,
      rather than bone inflammation in primary CRS.

PMID- 24449471
TI  - Wolfberries potentiate mitophagy and enhance mitochondrial biogenesis leading to
      prevention of hepatic steatosis in obese mice: the role of AMP-activated protein
      kinase alpha2 subunit.
AB  - SCOPE: The aim of this study is to investigate whether AMP-activated protein
      kinase alpha2 (AMPKalpha2) is essential for wolfberry's protective effects on
      mitochondrial dysfunction and subsequent hepatic steatosis in mice. METHODS AND
      RESULTS: Six-week-old male AMPKalpha2 knockout mice and genetic background
      C57BL/6J (B6) mice were fed a control, high-fat diet (HD, 45% (kilocalorie) fat),
      and/or HD with 5% (kilocalarie) wolfberry diets for 18 wk. At termination, blood
      and liver tissues were sampled for analysis by ELISA, HPLC, microscopy, real-time
      PCR, and Western blot. HD lowered hepatic lutein and zeaxanthin contents,
      inhibited protein expression of beta,beta-carotene 9',10'-oxygenase 2 (BCO2) and
      heat shock protein 60 in mitochondria, increased reactive oxygen species level,
      and suppressed mitophagy and mitochondrial biogenesis as determined by
      accumulation of p62, inhibited phosphorylation of Unc-51-like kinase 1 on Ser555,
      and declined expression of peroxisome proliferator-activated receptor gamma
      coactivator 1 alpha, resulting in hepatic steatosis in B6 and knockout mice.
      Dietary wolfberry elevated the xanthophyll concentrations and enhanced expression
      of BCO2 and heat shock protein 60, attenuated mitochondrial oxidative stress,
      activated AMPKalpha2, potentiated mitophagy and mitochondrial biogenesis, and
      enhanced lipid oxidation and secretion in the liver of B6 mice. CONCLUSION:
      Dietary wolfberry selectively activated AMPKalpha2, which resulted in enhanced
      mitochondrial biogenesis and potentiated mitophagy, leading to the prevention of
      hepatic steatosis in obese mice.

PMID- 24449472
TI  - TP53 mutants in the tower of babel of cancer progression.
AB  - Loss-of-function, partial-function, altered-function, dominant-negative,
      temperature sensitive, interfering, contact, structural, unfolded, misfolded,
      dimeric, monomeric, non-cooperative, unstable, supertrans, superstable,
      intragenic suppressor. TP53 mutants are many, more than 2,000 in fact, and they
      can be very diverse. Sporadic; germline; gain-of-function (GoF); oncogenic; rebel
      angel; yin and yang; prion-like; metastasis-inducer; mediator of chemo
      resistance; modifier of stemness. TP53 mutants can impact important cancer
      clinical variables, in multiple, often subtle ways, as revealed by cell-based
      assays as well as animal models. Here, we review studies investigating TP53
      mutants for their effect on sequence-specific transactivation function, and
      especially recent findings on how TP53 mutants can exhibit GoF properties. We
      also review reports on TP53 mutants' impact on cancer cell transcriptomes and
      studies with Li-Fraumeni patients trying to classify and predict phenotypes in
      relation to experimentally determined transcription fingerprints. Finally, we
      provide an example of the complexity of correlating TP53 mutant functionality to
      clinical variables in sporadic cancer patients. Conflicting results and
      limitations of experimental approaches notwithstanding, the study of TP53 mutants
      has provided a rich body of knowledge, mostly available in the public domain and
      accessible through databases, which is beginning to impact cancer intervention
      strategies. 

PMID- 24449473
TI  - Gangliosides as a potential new class of stem cell markers: the case of GD1a in
      human bone marrow mesenchymal stem cells.
AB  - Owing to their exposure on the cell surface and the possibility of being directly
      recognized with specific antibodies, glycosphingolipids have aroused great
      interest in the field of stem cell biology. In the search for specific markers of
      the differentiation of human bone marrow mesenchymal stem cells (hBMSCs) toward
      osteoblasts, we studied their glycosphingolipid pattern, with particular
      attention to gangliosides. After lipid extraction and fractionation,
      gangliosides, metabolically (3)H-labeled in the sphingosine moiety, were
      separated by high-performance TLC and chemically characterized by MALDI MS. Upon
      induction of osteogenic differentiation, a 3-fold increase of ganglioside GD1a
      was observed. Therefore, the hypothesis of GD1a involvement in hBMSCs commitment
      toward the osteogenic phenotype was tested by comparison of the osteogenic
      propensity of GD1a-highly expressing versus GD1a-low expressing hBMSCs and direct
      addition of GD1a in the differentiation medium. It was found that either the high
      expression of GD1a in hBMSCs or the addition of GD1a in the differentiation
      medium favored osteogenesis, providing a remarkable increase of alkaline
      phosphatase. It was also observed that ganglioside GD2, although detectable in
      hBMSCs by immunohistochemistry with an anti-GD2 antibody, could not be recognized
      by chemical analysis, likely reflecting a case, not uncommon, of molecular
      mimicry. 

PMID- 24449474
TI  - Novozym 435-catalyzed syntheses of polyesters and polyamides of medicinal and
      industrial relevance.
AB  - The adverse impact of chemical and biochemical waste on the environment and human
      health poses a serious challenge in today's World. The best way to address these
      challenges is to reduce the waste by developing more efficient processes and
      technologies, based on the principles of "green chemistry". Some of these
      synthetic approaches involving the chemoenzymatic synthetic methodologies are
      discussed herein. These lead to the formation of unique nanomaterials with
      diverse applications, such as drugs/gene delivery systems, flame retardant
      materials, conducting polymers, controlled release systems, diagnostic agents,
      and polymeric electrolytes for nanocrystalline solar cells. 

PMID- 24449475
TI  - Motor unit potential induced neurotonia (MINT).

PMID- 24449476
TI  - Engineering of a butyraldehyde dehydrogenase of Clostridium
      saccharoperbutylacetonicum to fit an engineered 1,4-butanediol pathway in
      Escherichia coli.
AB  - 1,4-Butanediol (1,4-BDO) is currently produced from succinate via six enzymatic
      reactions in an engineered Escherichia coli strain. Butyraldehyde dehydrogenase
      (Bld) and butanol dehydrogenase of Clostridium saccharoperbutylacetonicum were
      selected based on their activities of catalyzing the final two reactions in the
      1,4-BDO pathway. To fit Bld into the non-natural 1,4-BDO pathway, we engineered
      it through random mutagenesis. Five Bld mutants were then isolated using a
      colorimetric Schiff's reagent-based method. Subsequent site-directed mutagenesis
      of Bld generated the two best Bld mutants, L273I and L273T, which produced 1,4
      BDO titers fourfold greater than those of wild-type Bld. The enhanced 1,4-BDO
      titers obtained using L273I and L273T clearly correlated with their enhanced
      activities, which were caused by amino acid mutations at position 273 of Bld. The
      highest titer of 1,4-BDO (660 +/- 40 mg/L) was obtained in a knock-out E. coli
      strain [DeltaldhA DeltapflB DeltaadhE DeltalpdA::K. lpd(E354K) Deltamdh DeltaarcA
      gltA(R164L)] coexpressing Bld273T+Bdh.

PMID- 24449477
TI  - Prevention of no-reflow phenomenon in culprit lesions involving a large side
      branch.
AB  - No-reflow/slow-flow phenomenon (NF) is a poor prognostic factor in patients
      undergoing percutaneous coronary intervention. Distal protection devices (DPDs)
      prevent myocardial injury due to microembolic debris. When the target lesion
      involves a large side branch, DPDs can only protect the main vessel but not the
      side branch. In the present report, we describe the use of a two-step deflation
      in kissing-balloon technique for preventing NF in 4 patients (M/F = 4/0, 65 +/- 6
      years) in which the culprit lesions with NF risk involved a bifurcation. The
      procedures were uneventful and the 4 patients were discharged <=24 h without ECG
      change and elevation of serum level of creatine kinase. The sequential deflation
      of kissing-balloon technique may constitute a possible solution for the NF
      related with the side branch on bifurcation lesions.

PMID- 24449478
TI  - Highly elastic liquid crystals with a sub-nanonewton bending elastic constant
      mediated by the resident molecular assemblies.
AB  - A surprisingly high bending elastic constant (K33 ) is obtained in a newly
      synthesized compound shown here. Mixtures containing a few percent of this
      compound confirm the influence of the unusual K33 values, and show an improved
      electro-optic response. The origin of the huge K33 is discussed based on the
      formation of a smectic cluster structure formed in the nematic phase. 

PMID- 24449479
TI  - The emergence of Leishmania major and Leishmania donovani in southern Turkey.
AB  - BACKGROUND: In southern Turkey, Leishmania tropica and L. infantum are both the
      causative agents of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL),
      respectively. However, L. major and L. donovani were known to exist after the
      influx of Syrian refugees. METHODS: Between the years of July 2003 and July 2013,
      a total of 167 smears and 113 bone marrow samples were taken from CL and VL
      suspected cases, respectively. Samples were analysed through real-time PCR and
      ITS1 DNA sequencing. RESULTS: One hundred and seven 64% (107/167) smears and 56%
      (63/113) bone marrow samples were positive for leishmaniasis according to the
      real-time PCR. Three different Leishmania species were found in the 107 CL cases
      by real-time PCR: 42% (45/107) L. tropica, 36.5% (39/107) L. infantum and 21.5%
      (23/107) L. major. In addition, three different Leishmania species were
      identified in the 63 VL cases: 60.3% (38/63) L. infantum, 30.2% (19/63) L.
      donovani and 9.5% (6/63) L. tropica using real-time PCR. The results of real-time
      PCR were confirmed with Leishmania ITS1 DNA sequencing. CONCLUSIONS: This study
      revealed that in southern Turkey, L. major and L. donovani were the aetiological
      agents of CL and VL, respectively. It was assumed that emergence of L. major and
      L. donovani was due to influx of Syrian refugees, as well as the effects of
      global warming.

PMID- 24449480
TI  - Intestinal lymphangiectasia and reversible high liver stiffness.
AB  - Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy
      characterized by tortuous and dilated lymph channels of the small bowel. The main
      symptoms are bilateral lower limb edema, serosal effusions, and vitamin D
      malabsorption resulting in osteoporosis. We report here a case of long-lasting
      misdiagnosed PIL with a peculiar liver picture, characterized by a very high
      stiffness value at transient elastography, which decreased with clinical
      improvement. The complex interplay between lymphatic and hepatic circulatory
      system is discussed.

PMID- 24449481
TI  - Carboxylic acid free novel isocyanide-based reactions.
AB  - In order to develop a practical method for the construction of drug-like and
      heterocyclic compounds, we have designed a novel Passerini- or Ugi-type reaction
      system where a compound (which we write in the general form as Z-X) composed of
      an electrophilic (Z) and a nucleophilic group (X) could essentially perform the
      same function as the carboxylic acid. Based on this concept, we have developed
      the O-silylative Passerini reaction and the borinic acid catalyzed alpha-addition
      of isocyanides to aldehydes and water. In addition, we have designed and
      demonstrated the addition reaction of isocyanides to nitrones in the presence of
      TMSCl to afford the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxyamides.
      Furthermore, a novel [5 + 1] cycloaddition of isocyanide was explored with C,N
      cyclic N'-acyl azomethine imines as a "1,5-dipole" via a strategy involving
      intramolecular trapping of the isocyanide.

PMID- 24449482
TI  - Markers of disease severity and socioeconomic factors in allergic fungal
      rhinosinusitis.
AB  - BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a refractory subtype of
      chronic rhinosinusitis. There is a paucity of data investigating the association
      of epidemiologic markers of disease severity. The primary objective of this study
      is to evaluate components of disease severity with socioeconomic status and
      health care access. METHODS: A retrospective analysis was performed on patients
      diagnosed with AFRS by Bent and Kuhn criteria from 2000 to 2013. Severity of
      disease was measured by orbitocranial involvement, bone erosion, Lund-Mackay
      score, serum immunoglobulin E (IgE), and mold hypersensitivity. The North
      Carolina State Data Center provided county-specific socioeconomic and demographic
      data. Fisher's exact test, Wilcoxon rank sum test, Pearson correlations, and
      multivariable linear regression models were used to explore associations between
      variables. RESULTS: Of 93 patients, 58% were African American and 39% Caucasian
      with a male:female ratio of 1.4:1 and average age at presentation of 29 years.
      Race, age, insurance status, and gender were not associated with severity of
      disease. Bone erosion was correlated with residence in counties with lower income
      per capita (p = 0.01). Patients with orbitocranial involvement resided in more
      rural counties (p = 0.01) with less primary care providers per capita (p = 0.02).
      Residence in counties with older or poorer quality housing was associated with a
      higher prevalence of bone erosion (p = 0.02). CONCLUSION: Within our cohort of
      patients residing in North Carolina, markers of disease severity (bone erosion
      and orbitocranial involvement) in AFRS were associated with lower income, rural
      counties, poor housing quality, and less health care access.

PMID- 24449484
TI  - Mechanisms for enhanced performance of platinum-based electrocatalysts in proton
      exchange membrane fuel cells.
AB  - As a new generation of power sources, fuel cells have shown great promise for
      application in transportation. However, the expensive catalyst materials,
      especially the cathode catalysts for oxygen reduction reaction (ORR), severely
      limit the widespread commercialization of fuel cells. Therefore, this review
      article focuses on platinum (Pt)-based electrocatalysts for ORR with better
      catalytic performance and lower cost. Major breakthroughs in the improvement of
      activity and durability of electrocatalysts are discussed. Specifically, on one
      hand, the enhanced activity of Pt has been achieved through crystallographic
      control, ligand effect, or geometric effect; on the other hand, improved
      durability of Pt-based cathode catalysts has been realized by means of the
      incorporation of another noble metal or the morphological control of
      nanostructures. Furthermore, based on these improvement mechanisms, rationally
      designed Pt-based nanoparticles are summarized in terms of different synthetic
      strategies such as wet-chemical synthesis, Pt-skin catalysts, electrochemically
      dealloyed nanomaterials, and Pt-monolayer deposition. These nanoparticulate
      electrocatalysts show greatly enhanced catalytic performance towards ORR, aiming
      not only to outperform the commercial Pt/C, but also to exceed the US Department
      of Energy 2015 technical target ($30/kW and 5000 h). 

PMID- 24449483
TI  - Impact of obesity on the survival of patients with early-stage squamous cell
      carcinoma of the oral tongue.
AB  - BACKGROUND: Although obesity increases risk and negatively affects survival for
      many malignancies, the prognostic implications in squamous cell carcinoma (SCC)
      of the oral tongue, a disease often associated with prediagnosis weight loss, are
      unknown. METHODS: Patients with T1-T2 oral tongue SCC underwent curative-intent
      resection in this single-institution study. All patients underwent nutritional
      assessment prior to surgery. Body mass index (BMI) was calculated from measured
      height and weight and categorized as obese (>= 30 kg/m(2) ), overweight (25-29.9
      kg/m(2) ), or normal (18.5-24.9 kg/m(2) ). Clinical outcomes, including disease
      specific survival, recurrence-free survival, and overall survival, were compared
      by BMI group using Cox regression. RESULTS: From 2000 to 2009, 155 patients (90
      men, 65 women) of median age 57 years (range, 18-86 years) were included.
      Baseline characteristics were similar by BMI group. Obesity was significantly
      associated with adverse disease-specific survival compared with normal weight in
      univariable (hazard ratio [HR] = 2.65, 95% confidence interval [CI] = 1.07-6.59;
      P = .04) and multivariable analyses (HR = 5.01; 95% CI = 1.69-14.81; P = .004). A
      consistent association was seen between obesity and worse recurrence-free
      survival (HR = 1.87; 95% CI = 0.90-3.88) and between obesity and worse overall
      survival (HR = 2.03; 95% CI = 0.88-4.65) though without reaching statistical
      significance (P = .09 and P = .10, respectively) in multivariable analyses.
      CONCLUSIONS: In this retrospective study, obesity was an adverse independent
      prognostic variable. This association may not have been previously appreciated
      due to confounding by multiple factors including prediagnosis weight loss.

PMID- 24449485
TI  - Biomaterial microenvironments to support the generation of new neurons in the
      adult brain.
AB  - Neural stem cells (NSC) in two regions of the adult mammalian brain--the
      subventricular zone (SVZ) and hippocampus--continuously generate new neurons,
      enabled by a complex repertoire of factors that precisely regulate the
      activation, proliferation, differentiation, and integration of the newborn cells.
      A growing number of studies also report low-level neurogenesis in regions of the
      adult brain outside these established neurogenic niches--potentially via NSC
      recruitment or activation of local, quiescent NSCs--under perturbations such as
      ischemia, cell death, or viral gene delivery of proneural growth factors. We have
      explored whether implantation of engineered biomaterials can stimulate
      neurogenesis in normally quiescent regions of the brain. Specifically,
      recombinant versions of factors found within the NSC microenvironment, Sonic
      hedgehog, and ephrin-B2 were conjugated to long polymers, thereby creating highly
      bioactive, multivalent ligands that begin to emulate components of the neurogenic
      niche. In this engineered biomaterial microenvironment, new neuron formation was
      observed in normally non-neurogenic regions of the brain, the striatum, and the
      cortex, and combining these multivalent biomaterials with stromal cell-derived
      factor-1alpha increased neuronal commitment of newly divided cells seven- to
      eightfold in these regions. Additionally, the decreased hippocampal neurogenesis
      of geriatric rodents was partially rescued toward levels of young animals. We
      thus demonstrate for the first time de novo neurogenesis in both the cortex and
      striatum of adult rodents stimulated solely by delivery of synthetic biomaterial
      forms of proteins naturally found within adult neurogenic niches, offering the
      potential to replace neurons lost in neurodegenerative disease or injury as an
      alternative to cell implantation.

PMID- 24449486
TI  - Plasticity of cerebrovascular smooth muscle cells after subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is most often followed by a delayed phase of
      cerebral ischemia which is associated with high morbidity and mortality rates.
      The causes underlying this delayed phase are still unsettled, but are believed to
      include cerebral vasospasm, cortical spreading depression, inflammatory
      reactions, and microthrombosis. Additionally, a large body of evidence indicates
      that vascular plasticity plays an important role in SAH pathophysiology, and this
      review aims to summarize our current knowledge on the phenotypic changes of
      vascular smooth muscle cells of the cerebral vasculature following SAH. In light
      of the emerging view that the whole cerebral vasculature and the cells of the
      brain parenchyma should be viewed as one integrated neurovascular network,
      phenotypical changes are discussed both for the cerebral arteries and the
      microvasculature. Furthermore, the intracellular signaling involved in the
      vascular plasticity is discussed with a focus on the Raf-MEK1/2-ERK1/2 pathway
      which seems to play a crucial role in SAH pathology. 

PMID- 24449487
TI  - Palladium-catalyzed one-pot three- or four-component coupling of aryl iodides,
      alkynes, and amines through C-N bond cleavage: efficient synthesis of indole
      derivatives.
AB  - An efficient synthesis of N-substituted indole derivatives was realized by
      combining the Pd-catalyzed one-pot multicomponent coupling approach with cleavage
      of the C(sp(3))-N bonds. Three or four components of aryl iodides, alkynes, and
      amines were involved in this coupling process. The cyclopentadiene-phosphine
      ligand showed high efficiency. A variety of aryl iodides, including cyclic and
      acyclic tertiary amino aryl iodides, and substituted 1-bromo-2-iodobenzene
      derivatives could be used. Both symmetric and unsymmetric alkynes substituted
      with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary
      amines such as piperidine, morpholine, 4-methylpiperidine, 1-methylpiperazine, 2
      methylpiperidine, and acyclic amines including secondary and primary amines all
      showed good reactivity. Further application of the resulting indole derivatives
      was demonstrated by the synthesis of benzosilolo[2,3-b]indole.

PMID- 24449488
TI  - Muscle intrusion as a potential cause of carpal tunnel syndrome.
AB  - INTRODUCTION: The aim of this study was to determine whether there is an
      association between flexor digitorum and lumbrical muscle intrusion into the
      carpal tunnel and carpal tunnel syndrome (CTS). METHODS: Five hundred thirteen
      manual laborers (1026 wrists) were evaluated with ultrasound to determine whether
      those with CTS had more muscle intrusion into the carpal tunnel than those
      without CTS. One hundred ninety of the participants without CTS at baseline (363
      wrists) were followed over 1 year to determine whether muscle intrusion at
      baseline predicted the development of CTS. RESULTS: Participants with CTS had
      more muscle within the carpal tunnel with the wrist in the neutral (P=0.026) and
      flexed (P=0.018) positions than those without CTS. Baseline muscle intrusion did
      not predict development of CTS at 1 year. CONCLUSIONS: Muscle intrusion into the
      carpal tunnel is associated with CTS, but muscle intrusion alone does not predict
      the development of CTS over the course of a year.

PMID- 24449489
TI  - Control of plant defense mechanisms and fire blight pathogenesis through the
      regulation of 6-thioguanine biosynthesis in Erwinia amylovora.
AB  - Fire blight is a devastating disease of Rosaceae plants, such as apple and pear
      trees. It is characterized by necrosis of plant tissue, caused by the
      phytopathogenic bacterium Erwinia amylovora. The plant pathogen produces the well
      known antimetabolite 6-thioguanine (6TG), which plays a key role in fire blight
      pathogenesis. Here we report that YcfR, a member of the LTTR family, is a major
      regulator of 6TG biosynthesis in E. amylovora. Inactivation of the regulator gene
      (ycfR) led to dramatically decreased 6TG production. Infection assays with apple
      plants (Malus domestica cultivar Holsteiner Cox) and cell cultures of Sorbus
      aucuparia (mountain ash, rowan) revealed abortive fire blight pathogenesis and
      reduced plant response (biphenyl and dibenzofuran phytoalexin production). In the
      presence of the DeltaycfR mutant, apple trees were capable of activating the
      abscission machinery to remove infected tissue. In addition to unveiling the
      regulation of 6TG biosynthesis in a major plant pathogen, we demonstrate for the
      first time that this antimetabolite plays a pivotal role in dysregulating the
      plant response to infection.

PMID- 24449491
TI  - Ultrahigh rate capabilities of lithium-ion batteries from 3D ordered
      hierarchically porous electrodes with entrapped active nanoparticles
      configuration.
AB  - Three dimensional (3D) ordered hierarchically porous electrodes with an entrapped
      active nanoparticles configuration afford an extremely effective conductive 3D
      network from the micrometer to the nano meter scale for fast electron and Li-ion
      transport, and also allow the development of a stable solid electrolyte
      interphase over the electrode materials, therefore exhibiting extraordinary rate
      capabilities. 

PMID- 24449492
TI  - 17-beta-estradiol analog inhibits cell proliferation by induction of apoptosis in
      breast cell lines.
AB  - Microtubules are important targets when studying potential anticancer agents
      since disturbance of these microtubule dynamics results in cell cycle arrest and
      cell death. 2-Methoxyestradiol is a naturally occurring metabolite that exerts
      antiproliferative activity and induces apoptosis. Due to limited biological
      accessibly and rapid metabolic degradation, several analogs were synthesized.
      This study investigated the antiproliferative influence of an 2-methoxyestradiol
      analog, (8R, 13S, 14S, 17S)-2-Ethyl-13-methyl-7, 8, 9, 11, 12,13, 14, 15, 16, 17
      decahydro-6H-cyclopenta[a]phenanthrane-3, 17-diyl bis(sulfamate) (EMBS) on cell
      proliferation, morphology and apoptosis induction in a estrogen receptor-positive
      breast adenocarcinoma cells line (MCF-7), estrogen receptor-negative highly
      metastatic breast cell line (MDA-MB-231) and a non-tumorigenic breast epithelial
      cell line (MCF-12A). Spectrophotometry results indicated that EMBS exerted
      differential antiproliferative activity in the three cell lines. Cell growth of
      the breast adenocarcinoma and highly metastatic breast cell line reached a
      plateau effect at 0.4 MUM after 24 h of exposure. Light microscopy and
      polarization-optical transmitted light differential interference contrast
      demonstrated compromised cell density, cells blocked in metaphase and the
      presence of apoptotic characteristics after EMBS exposure for 24 h in all three
      cell lines. Transmission electron microscopy and scanning electron microscopy
      revealed hallmarks of apoptosis namely the presence of apoptotic bodies, shrunken
      cells and cell debris in EMBS-exposed cells. This investigation demonstrated that
      EMBS does exert antimitotic activity and induces apoptosis contributing to
      elucidating the signal transduction of EMBS in tumorigenic and non-tumorigenic
      breast cell lines. Findings warrant in-depth analysis of specific targets in
      vitro and subsequent in vivo investigation for anticancer therapy.

PMID- 24449493
TI  - Lack of basic healthcare knowledge regarding rotavirus diarrhoea.

PMID- 24449495
TI  - Adjustments to diabetes medications in response to increases in hemoglobin a1c:
      an epidemiologic study.
AB  - OBJECTIVE: The primary objective was to assess associations between increases in
      glycated hemoglobin (HbA1c) levels and medication adjustments among patients with
      diabetes. A secondary objective was to measure the effect of adjustments on
      subsequent HbA1c levels. METHODS: A retrospective analysis of administrative data
      from a large health insurer in Hawaii of 7654 patients with diabetes mellitus
      type II, HbA1c levels greater than 7%, and who were taking oral diabetic
      medications. Patients were eligible if they had an HbA1c measurement in 2009, a
      prior measure 30 or more days previously, and at least 30 days of follow-up to
      identify medication adjustments. Patients were classified into 3 groups based on
      their extent of change in HbA1c levels. Patients were followed to determine the
      frequency of medication adjustments and to observe the possible benefit of making
      adjustments on subsequent HbA1c levels. RESULTS: Medication adjustments were the
      exception, occurring among less than a fourth of patients. Compared with patients
      without HbA1c increases, patients with <1% HbA1c increases made adjustments 20%
      more frequently, and patients with increased HbA1c levels of 1% or more made
      adjustments 60% more frequently. Patients with similar HbA1c increases were more
      likely to adjust their medications if they had higher baseline HbA1c levels.
      Medication adjustments were mostly for oral diabetes medications; insulin use was
      seldom initiated, and then primarily by patients with HbA1c levels of 9% or
      higher. Patients with medication adjustments averaged about 0.40% lower HbA1c
      levels when reassessed after 120 days or more. CONCLUSION: The results show
      limited responsiveness to increases in HbA1c levels and a low initiation rate of
      insulin use. Patients adjusting their medications, however, had clinically
      significant improvements in their HbA1c levels. Clinical inertia and patient
      concerns are discussed as factors possibly limiting the frequency of medication
      adjustments.

PMID- 24449494
TI  - Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative
      diseases.
AB  - The molecular mechanisms that regulate synapse formation have been well
      documented. However, little is known about the factors that modulate synaptic
      stability. Synapse loss is an early and invariant feature of neurodegenerative
      diseases including Alzheimer's (AD) and Parkinson's disease. Notably, in AD the
      extent of synapse loss correlates with the severity of the disease. Hence,
      understanding the molecular mechanisms that underlie synaptic maintenance is
      crucial to reveal potential targets that will allow the development of therapies
      to protect synapses. Wnts play a central role in the formation and function of
      neuronal circuits. Moreover, Wnt signaling components are expressed in the adult
      brain suggesting their role in synaptic maintenance in the adult. Indeed,
      blockade of Wnts with the Wnt antagonist Dickkopf-1 (Dkk1) causes synapse
      disassembly in mature hippocampal cells. Dkk1 is elevated in brain biopsies from
      AD patients and animal models. Consistent with these findings, Amyloid-beta
      (Abeta) oligomers induce the rapid expression of Dkk1. Importantly, Dkk1
      neutralizing antibodies protect synapses against Abeta toxicity, indicating that
      Dkk1 is required for Abeta-mediated synapse loss. In this review, we discuss the
      role of Wnt signaling in synapse maintenance in the adult brain, particularly in
      relation to synaptic loss in neurodegenerative diseases. 

PMID- 24449496
TI  - Medication nonadherence due to misunderstanding of the salt form.

PMID- 24449497
TI  - Epigenetic reprogramming modulates malignant properties of human liver cancer.
AB  - Reversal of DNA hypermethylation and associated gene silencing is an emerging
      cancer therapy approach. Here we addressed the impact of epigenetic alterations
      and cellular context on functional and transcriptional reprogramming of
      hepatocellular carcinoma (HCC) cells. Our strategy employed a 3-day treatment of
      established and primary human HCC-derived cell lines grown as a monolayer at
      various cell densities with the DNMT1 inhibitor zebularine (ZEB) followed by a 3D
      culture to identify cells endowed with self-renewal potential. Differences in
      self-renewal, gene expression, tumorigenicity, and metastatic potential of
      spheres at generations G1-G5 were examined. Transient ZEB exposure produced
      differential cell density-dependent responses. In cells grown at low density, ZEB
      caused a remarkable increase in self-renewal and tumorigenicity associated with
      long-lasting gene expression changes characterized by a stable overexpression of
      cancer stem cell-related and key epithelial-mesenchymal transition genes. These
      effects persisted after restoration of DNMT1 expression. In contrast, at high
      cell density, ZEB caused a gradual decrease in self-renewal and tumorigenicty,
      and up-regulation of apoptosis- and differentiation-related genes. A permanent
      reduction of DNMT1 protein using short hairpin RNA (shRNA)-mediated DNMT1
      silencing rendered HCC cells insensitive both to cell density and ZEB effects.
      Similarly, WRL68 and HepG2 hepatoblastoma cells expressing low DNMT1 basal levels
      also possessed a high self-renewal, irrespective of cell density or ZEB exposure.
      Spheres formed by low-density cells treated with ZEB or shDNMT1 displayed a high
      molecular similarity which was sustained through consecutive generations,
      confirming the essential role of DNMT1 depletion in the enhancement of cancer
      stem cell properties. CONCLUSION: These results identify DNA methylation as a key
      epigenetic regulatory mechanism determining the pool of cancer stem cells in
      liver cancer and possibly other solid tumors.

PMID- 24449498
TI  - Landmarks for endoscopic approach to the parapharyngeal internal carotid artery:
      a radiographic and cadaveric study.
AB  - OBJECTIVES/HYPOTHESIS: To define transnasal endoscopic surgical landmarks for the
      parapharyngeal segment of the internal carotid artery (ppICA) using radiographic
      analysis and cadaveric dissection. STUDY DESIGN: Cadaveric and radiographic
      study. METHODS: One hundred seventy-nine computed tomography angiography studies
      of the head and neck were analyzed using Osirix third-party software (Pixmeo,
      Geneva, Switzerland). Dissection of a cadaveric specimen was used as a correlate
      to radiographic findings. The posterior aspect of the lateral pterygoid process
      and posterior border of the mandibular ramus were used as bony landmarks for the
      ppICA. RESULTS: At the level of the nasal floor, the distance from the ppICA to
      the posterolateral pterygoid process and to the posterior mandibular ramus was
      2.36 cm and 1.94 cm, respectively, in males, and 2.37 cm and 1.99 cm,
      respectively, in females. At the level of the skull base, the distance from the
      ppICA to the posterolateral pterygoid process and to the posterior mandible was
      2.33 cm and 1.49 cm, respectively, in males, and 2.20 cm and 1.57 cm,
      respectively, in females. Cadaver dissection demonstrated the utility of
      identifying these landmarks. CONCLUSIONS: The posterior border of the mandibular
      ramus and the posterolateral aspect of the pterygoid process may serve as
      consistent bony landmarks for identification of the ppICA.

PMID- 24449500
TI  - Asymmetric nitrene transfer reactions: sulfimidation, aziridination and C-H
      amination using azide compounds as nitrene precursors.
AB  - Nitrogen functional groups are found in many biologically active compounds and
      their stereochemistry has a profound effect on biological activity. Nitrene
      transfer reactions such as aziridination, C-H bond amination, and sulfimidation
      are useful methods for introducing nitrogen functional groups, and the
      enantiocontrol of the reactions has been extensively investigated. Although high
      enantioselectivity has been achieved, most of the reactions use (N
      arylsulfonylimino)phenyliodinane, which co-produces iodobenzene, as a nitrene
      precursor and have a low atom economy. Azide compounds, which give nitrene
      species by releasing nitrogen, are ideal precursors but rather stable. Their
      decomposition needs UV irradiation, heating in the presence of a metal complex,
      or Lewis acid treatment. The examples of previous azide decomposition prompted us
      to examine Lewis acid and low-valent transition-metal complexes as catalysts for
      azide decomposition. Thus, we designed new ruthenium complexes that are composed
      of a low-valent Ru(II) ion, apical CO ligand, and an asymmetry-inducing salen
      ligand. With these ruthenium complexes and azides, we have achieved highly
      enantioselective nitrene transfer reactions under mild conditions. Recently,
      iridium-salen complexes were added to our toolbox. 

PMID- 24449501
TI  - Cleavage of C-O bonds in lignin model compounds catalyzed by methyldioxorhenium
      in homogeneous phase.
AB  - Methyldioxorhenium (MDO)-catalyzed C-O bond cleavage of a variety of lignin beta
      O-4-model compounds yields phenolic and aldehydic compounds in homogeneous phase
      under mild reaction conditions. MDO is in situ generated by reduction of
      methyltrioxorhenium (MTO) and is remarkably stable under the applied reaction
      conditions allowing its reuse for least five times without significant activity
      loss. Based on the observed and isolated intermediates, 17 O- and 2 H-isotope
      labeling experiments, DFT calculations, and several spectroscopic studies, a
      reaction mechanism is proposed.

PMID- 24449499
TI  - Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial
      cell heterogeneity in breast cancer xenografts.
AB  - Plasma membrane-localized vascular endothelial growth factor receptors (VEGFR)
      play a critical role in transducing VEGF signaling toward pro and antiangiogenic
      outcomes and quantitative characterization of these receptors is critical toward
      identifying biomarkers for antiangiogenic therapies, understanding mechanisms of
      action of antiangiogenic drugs, and advancing predictive computational models.
      While in vitro analysis of cell surface-VEGFRs has been performed, little is
      known about the levels of cell surface-VEGFR on tumor cells. Therefore, we
      inoculate nude mice with the human triple-negative breast cancer, MDA-MB-231,
      cell line; isolate human tumor cells and mouse tumor endothelial cells from
      xenografts; and quantitatively characterize the VEGFR localization on these
      cells. We observe 15,000 surface-VEGFR1/tumor endothelial cell versus 8200
      surface-VEGFR1/tumor endothelial cell at 3 and 6 weeks of tumor growth,
      respectively; and we quantify 1200-1700 surface-VEGFR2/tumor endothelial cell.
      The tumor cell levels of VEGFR1 and VEGFR2 are relatively constant between 3 and
      6 weeks: 2000-2200 surface-VEGFR1/tumor cell and ~1000 surface-VEGFR2/tumor cell.
      Cell-by-cell analysis provides additional insight into tumor heterogeneity by
      identifying four cellular subpopulations based on size and levels of cell
      membrane-localized VEGFR. Furthermore, when these ex vivo data are compared to in
      vitro data, we observe little to no VEGFRs on MDA-MB-231 cells, and the MDA-MB
      231 VEGFR surface levels are not regulated by a saturating dose of VEGF. Overall,
      the quantification of these dissimilarities for the first time in tumor provides
      insight into the balance of modulatory (VEGFR1) and proangiogenic (VEGFR2)
      receptors.

PMID- 24449502
TI  - Production and characterization of recombinant human beta-defensin DEFB120.
AB  - Public health of human beings is threatened by superbugs. Novel human beta
      defensins, which contribute to host defense against pathogen invasion and innate
      immune protection, might be a potent natural candidate pool for new antibiotic
      lead screening. In the present work, we successfully expressed and purified a
      novel human beta-defensin, DEFB120, using the IMPACT-TWIN system in Escherichia
      coli and identified the purified homogeneous proteins using MALDI-TOF mass
      spectrometry. Then, we performed the fundamental studies on the structure and
      biological functions for the DEFB120 peptide. The recombinant DEFB120 peptide
      showed wide antimicrobial effects against E. coli, Staphylococcus aureus and
      Candida albicans strains without significant hemolytic activity. Furthermore, the
      high lipopolysaccharide (LPS)-binding affinity in vitro indicated that DEFB120
      might be associated with the inhibition of LPS-induced inflammatory response.
      These results may pave a way for exploiting the essential physiological functions
      of DEFB120 and also for the development of natural antibiotic pools.

PMID- 24449503
TI  - Bone marrow mesenchymal stem cells ameliorate inflammatory factor-induced
      dysfunction of INS-1 cells on chip.
AB  - Using a microfluidic chip, we have investigated whether bone marrow mesenchymal
      stem cells (BM-MSCs) could ameliorate IL-1beta/IFN-gamma-induced dysfunction of
      INS-1 cells. BM-MSCs were obtained from diabetes mellitus patients and their cell
      surface antigen expression profiles were analyzed by flow cytometric. INS-1 cells
      were cocultured with BM-MSCs on a microfluidic chip with persistent perfusion of
      medium containing 1 ng/mL IL-1beta and 2.5 U/mL IFN-gamma for 72 h. BM-MSCs could
      partially rescue INS-1 cells from cytokine-induced dysfunction and ameliorate the
      expression of insulin and PDX-1 gene in INS-1 cells. Thus BM-MSCs can be viewed
      as a promising stem cell source to depress inflammatory factor-induced
      dysfunction of pancreatic beta cells in diabetic patients.

PMID- 24449504
TI  - Estimation of intervention effects using recurrent event time data in the
      presence of event dependence and a cured fraction.
AB  - Recurrent event data with a fraction of subjects having zero event are often seen
      in randomized clinical trials. Those with zero event may belong to a cured (or
      non-susceptible) fraction. Event dependence refers to the situation that a
      person's past event history affects his future event occurrences. In the presence
      of event dependence, an intervention may have an impact on the event rate in the
      non-cured through two pathways-a primary effect directly on the outcome event and
      a secondary effect mediated through event dependence. The primary effect combined
      with the secondary effect is the total effect. We propose a frailty mixture model
      and a two-step estimation procedure for the estimation of the effect of an
      intervention on the probability of cure and the total effect on event rate in the
      non-cured. A summary measure of intervention effects is derived. The performance
      of the proposed model is evaluated by simulation. Data on respiratory
      exacerbations from a randomized, placebo-controlled trial are re-analyzed for
      illustration.

PMID- 24449505
TI  - Association between p53 codon 72 polymorphism and sarcoma risk among Caucasians.
AB  - Many published data on the association between p53 codon 72 polymorphism and
      sarcoma risk showed inconclusive results. The present study was designed to
      derive a more precise estimation of this connection among Caucasians. We
      conducted a literature search in PubMed, EMBASE, Web of Science, and CNKI
      databases for case-control studies examining the association between p53 codon 72
      polymorphism and sarcoma risk. The meta-analysis was performed using STATA 12.0
      software. Crude odds ratios (ORs) with corresponding 95% confidence intervals
      (CIs) were used to measure the strength of any association. The results of this
      meta-analysis did not provide statistical evidence for significant sarcoma risk
      associated with p53 codon 72 polymorphism (OR(Arg/Arg vs. Pro/Pro) = 1.00, 95% CI
      = 0.80-1.26, P(heterogeneity) = 0.980; OR(Arg/Arg + Arg/Pro vs. Pro/Pro) = 0.99,
      95% CI = 0.83-1.19, P(heterogeneity) = 0.990; OR(Arg/Arg vs. Arg/Pro + Pro/Pro) =
      1.09, 95% CI = 0.89-1.35, P(heterogeneity) = 0.532; OR(allele Arg vs. allele Pro)
      = 1.03, 95% CI = 0.90-1.18, P(heterogeneity) = 0.883; OR(Arg/Pro vs. Pro/Pro) =
      0.95, 95% CI = 0.71-1.27, P(heterogeneity) = 0.919). We also did not find
      significant links in further subgroup analyses by ethnicity, control source, and
      sarcoma type. The present meta-analysis of currently available data suggests that
      the p53 codon 72 polymorphism may not play a role in sarcoma development in
      Caucasians.

PMID- 24449506
TI  - Clinicopathological and prognostic significance of HER2 overexpression in gastric
      cancer: a meta-analysis of the literature.
AB  - Human epidermal growth factor receptor 2 (HER2) plays an important role in the
      aggressiveness and progression of gastric cancer. With the publication of trial
      results, we conducted a meta-analysis to investigate its prognostic significance
      for patients with gastric cancer. PubMed, Ovid, Web of Science, and Cochrane
      databases were searched. Statistical analysis was carried out by STATA version
      12.0 software. The Newcastle-Ottawa scale was used to assess the quality of
      evidence. Fifteen studies involving 5,290 patients met the inclusion criteria.
      The results showed that HER2 overexpression was significantly associated with
      patients' overall survival (HR = 1.56, 95% confidence interval (CI) 1.05-2.07; Z
      = 6.03; P = 0.000). The results also suggested that HER2 overexpression was
      associated with Bormann type (odds ratio (OR) = 1.76, 95% CI 1.19-2.59; Z = 2.85;
      P = 0.004), tumor differentiation (OR = 3.14, 95% CI 1.91-5.17; Z = 4.49; P =
      0.000), Lauren's classification (OR = 6.25, 95% CI 4.29-9.10; Z = 9.54; P =
      0.000), lymph node metastasis (OR = 1.43, 95% CI 1.15-1.77; Z = 3.23; P = 0.001),
      venous invasion (OR = 1.69, 95% CI 1.15-2.48; Z = 2.67; P = 0.008), and
      lymphovascular invasion (OR = 1.57, 95% CI 1.21-2.04; Z = 3.4; P = 0.001).
      However, it had no correlation with tumor size, depth of invasion, and tumor
      stage. This study showed that HER2 overexpression had an unfavorable prognostic
      role for patients with gastric cancer. HER2-positive expression was associated
      with Bormann type, Lauren's classification, tumor differentiation, lymph node
      status, venous invasion, and lymphovascular invasion.

PMID- 24449507
TI  - miR-132 targeting cyclin E1 suppresses cell proliferation in osteosarcoma cells.
AB  - In this study, we investigated the roles of miR-132 in tumor growth of
      osteosarcoma. We found that overexpression of miR-132 significantly suppressed in
      vitro cell proliferation and in vivo tumor growth. In addition, miR-132
      overexpression induced G1/S cell cycle arrest of osteosarcoma cells. Further
      study showed that miR-132 could interact with the 3'-untranslated region of
      cyclin E1 (CCNE1) gene and repress its expression. Re-expression of CCNE1
      (without the 3'UTR) could partially abrogate the miR-132-induced cell
      proliferation inhibition. Of significance, contrary to CCNE1, expression level of
      miR-132 was significantly lower in osteosarcoma tissues than in the adjacent
      normal tissues. Taken together, these results indicate that miR-132 functions as
      a tumor suppressor in osteosarcoma and that its suppressive effects are mediated
      chiefly by repressing CCNE1 expression. 

PMID- 24449508
TI  - Letter regarding Wen X.Y. et al. entitled "Matrix metalloproteinase 2 expression
      and survival of patients with osteosarcoma: a meta-analysis".

PMID- 24449509
TI  - Highly luminescent N-doped carbon quantum dots as an effective multifunctional
      fluorescence sensing platform.
AB  - The doping of carbon quantum dots with nitrogen provides a promising direction to
      improve fluorescence performance and broaden their applications in sensing
      systems. Herein we report a one-pot solvothermal synthesis of N-doped carbon
      quantum dots (NCQDs) and the synthesis of a series of NCQDs with different
      nitrogen contents. The as-prepared NCQDs were compared with carbon quantum dots
      (CQDs); the introduction of nitrogen atoms largely increased the quantum yield of
      NCQDs and highest emission efficiency is up to 36.3 %. The fluorescence
      enhancement may originate from more polyaromatic structures induced by
      incorporated nitrogen atoms and protonation of nitrogen atoms on dots. It was
      found that NCQDs can act as a multifunctional fluorescence sensing platform
      because they can be used to detect pH values, Ag(I), and Fe(III) in aqueous
      solution. The fluorescence intensity of NCQDs is inversely proportional to pH
      values across a broad range from 5.0 to 13.5, which indicates that NCQDs can be
      devised as an effective pH indicator. Selective detection of Ag(I) and Fe(III)
      was achieved based on their distinctive fluorescence influence because Ag(I) can
      significantly enhance the fluorescence whereas Fe(III) can greatly quench the
      fluorescence. The quantitative determination of Ag(I) can be accomplished with
      NCQDs by using the linear relationship between fluorescence intensity of NCQDs
      and concentration of Ag(I). The sensitive detection of H2O2 was developed by
      taking advantage of the distinct quenching ability of Fe(III) and Fe(II) toward
      the fluorescence of NCQDs. Cellular toxicity test showed NCQDs still retain low
      toxicity to cells despite the introduction of a great deal of nitrogen atoms.
      Moreover, bioimaging experiments demonstrated that NCQDs have stronger resistance
      to photobleaching than CQDs and more excellent fluorescence labeling performance.

PMID- 24449510
TI  - The origins of homochirality examined by using asymmetric autocatalysis.
AB  - Pyrimidyl alkanol was found to act as an asymmetric autocatalyst in the
      enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde.
      Asymmetric autocatalysis of 2-alkynylpyrimidyl alkanol with an extremely low
      enantiomeric excess (ca. 0.00005% ee) exhibits enormous asymmetric amplification
      to afford the same compound with >99.5% ee. This asymmetric autocatalysis with
      amplification of ee has been employed to examine the validity of proposed
      theories of the origins of homochirality. Circularly polarized light, quartz,
      sodium chlorate, cinnabar, chiral organic crystals and spontaneous absolute
      asymmetric synthesis were considered as possible candidates for the origin of
      chirality; each could act as a chiral source in asymmetric autocatalysis.
      Asymmetric autocatalysis can discriminate the isotope chirality arising from the
      small difference between carbon (carbon-13/carbon-12) and hydrogen (D/H)
      isotopes. Cryptochiral compounds were also discriminated by asymmetric
      autocatalysis. 

PMID- 24449511
TI  - A novel protocol for assessing exercise performance and dystropathophysiology in
      the mdx mouse.
AB  - INTRODUCTION: Dystrophinopathy in the young mdx mouse model of Duchenne muscular
      dystrophy is comparatively mild, requires induction, and is rarely assessed with
      tests of systemic muscle function in whole animals. METHODS: A modified TREAT-NMD
      induction protocol was used to evaluate respiratory and exercise performance,
      starting and ending with maximum oxygen consumption (VO2max ) tests. RESULTS: The
      initial and/or final VO2max , time to exhaustion, speed at exhaustion, and total
      expended calories were significantly lower in mdx mice. Episodic VO2 and VCO2
      fluctuations occurred during training and resulted in dissociated patterns of VO2
      and respiratory exchange ratio (RER). These fluctuations further resulted in
      significantly greater VO2 coefficient of variation and RER values and lower
      minimal VO2 values. CONCLUSIONS: Quantifying respiratory performance during
      exercise is a potentially useful means for studying pathophysiology in mdx mice,
      as it assesses intact animals over time, is more sensitive than some histological
      markers, and assesses systemic muscle function.

PMID- 24449512
TI  - Genetic dysregulation in recurrent respiratory papillomatosis.
AB  - OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a
      devastating disease, caused by infection of the upper aerodigestive tract with
      human papillomavirus types 6 and 11. There is no cure for RRP, and surgical
      removal is the mainstay of treatment. The purpose of this project was to compare
      genes of cell cycle, apoptosis, and inflammatory cytokines in laryngeal papilloma
      versus normal tissue for a better understanding of the molecular mechanisms of
      the disease to discover novel therapies. STUDY DESIGN: Basic science research
      study. METHODS: Papilloma tissue was obtained from patients requiring surgical
      debridement. For comparison, normal mucosa was obtained from the excised uvula of
      patients undergoing uvulopalatopharyngoplasty. Total RNA was extracted from both
      groups and then probed using customized reverse transcriptase real time
      polymerase chain reaction gene arrays. RESULTS: The custom arrays examine
      expression of 84 separate genes within the cell cycle, apoptosis, and
      inflammatory cytokine pathways. Our findings based on 11 papilloma samples run in
      comparison to normal mucosa shows that the MCL-1 gene of the apoptosis pathway is
      significantly downregulated. cytokine genes IL1-A, IL-8, IL-18, and IL-31 are
      also significantly dysregulated. CONCLUSIONS: Genes of cell cycle and apoptosis
      are generally upregulated and downregulated, respectively, as expected in
      papilloma tissue, with MCL-1 achieving significance when compared to normal
      tissue. The finding of particular interest is that inflammatory cytokine genes
      were significantly downregulated, including IL1-A, IL-18, and IL-31. This finding
      may explain why patients infected with the virus are unable to mediate a T-cell
      immune clearance of their disease.

PMID- 24449513
TI  - Modulation of pain threshold by virtual body ownership.
AB  - BACKGROUND: Appropriate sensorimotor correlations can result in the illusion of
      ownership of exogenous body parts. Nevertheless, whether and how the illusion of
      owning a new body part affects human perception, and in particular pain
      detection, is still poorly investigated. Recent findings have shown that seeing
      one's own body is analgesic, but it is not known whether this effect is
      transferable to newly embodied, but exogenous, body parts. In recent years,
      results from our laboratory have demonstrated that a virtual body can be felt as
      one's own, provided realistic multisensory correlations. METHODS: The current
      work aimed at investigating the impact of virtual body ownership on pain
      threshold. An immersive virtual environment allowed a first-person perspective of
      a virtual body that replaced the own. Passive movement of the index finger
      congruent with the movement of the virtual index finger was used in the
      'synchronous' condition to induce ownership of the virtual arm. The pain
      threshold was tested by thermal stimulation under four conditions: (1)
      synchronous movements of the real and virtual fingers; (2) asynchronous
      movements; (3) seeing a virtual object instead of an arm; and (4) not seeing any
      limb in real world. RESULTS: Our results show that, independently of attentional
      and stimulus adaptation processes, the ownership of a virtual arm per se can
      significantly increase the thermal pain threshold. CONCLUSIONS: This finding may
      be relevant for the development and improvement of digital solutions for
      rehabilitation and pain treatment.

PMID- 24449514
TI  - Water oxidation by amorphous cobalt-based oxides: volume activity and proton
      transfer to electrolyte bases.
AB  - Water oxidation in the neutral pH regime catalyzed by amorphous transition-metal
      oxides is of high interest in energy science. Crucial determinants of
      electrocatalytic activity were investigated for a cobalt-based oxide film
      electrodeposited at various thicknesses on inert electrodes. For water oxidation
      at low current densities, the turnover frequency (TOF) per cobalt ion of the bulk
      material stayed fully constant for variation of the thickness of the oxide film
      by a factor of 100 (from about 15 nm to 1.5 MUm). Thickness variation changed
      neither the nanostructure of the outer film surface nor the atomic structure of
      the oxide catalyst significantly. These findings imply catalytic activity of the
      bulk hydrated oxide material. Nonclassical dependence on pH was observed. For
      buffered electrolytes with pKa values of the buffer base ranging from 4.7
      (acetate) to 10.3 (hydrogen carbonate), the catalytic activity reflected the
      protonation state of the buffer base in the electrolyte solution directly and not
      the intrinsic catalytic properties of the oxide itself. It is proposed that
      catalysis of water oxidation occurs within the bulk hydrated oxide film at the
      margins of cobalt oxide fragments of molecular dimensions. At high current
      densities, the availability of a proton-accepting base at the catalyst
      electrolyte interface controls the rate of water oxidation. The reported findings
      may be of general relevance for water oxidation catalyzed at moderate pH by
      amorphous transition-metal oxides. 

PMID- 24449515
TI  - Physical fitness, overweight and the risk of eating disorders in adolescents. The
      AVENA and AFINOS studies.
AB  - What is already known about this subject Eating disorders are among the public
      health issues facing adolescents. An excess of body fat has been associated with
      an increased risk of these disorders. The association of physical fitness with
      eating disorders has not yet been analysed in adolescents. What this study adds
      This study confirms that the overweight and obesity increase the risk of
      developing eating disorders. The present study shows that there is an inverse
      association between physical fitness levels and the risk of eating disorders.
      This study suggests that physical fitness might attenuate the influence of
      overweight on the development of eating disorders in adolescents. BACKGROUND:
      Eating disorders together with the overweight and obesity are important health
      concerns in adolescents. OBJECTIVE: To analyse the individual and combined
      influence of overweight and physical fitness on the risk of developing eating
      disorders in Spanish adolescents. METHODS: The sample consisted of 3571
      adolescents (1864 females), aged 13 to 18.5 years, from Spain who participated in
      the AVENA and AFINOS studies. The risk of eating disorders was evaluated using
      the SCOFF questionnaire. Body mass index was calculated and the adolescents were
      classified into two groups: overweight (including obesity) and non-overweight
      according to Cole's cut-off points. Cardiorespiratory fitness in the AVENA Study
      was assessed by the 20-m shuttle-run test and the overall physical fitness level
      was self-reported in the AFINOS Study. RESULTS: Overweight adolescents had a
      higher risk of developing eating disorders than non-overweight adolescents (odds
      ratio [OR] = 4.91, 95% confidence interval [CI]: 3.63-6.61 in the AVENA Study and
      OR = 2.45, 95% CI: 1.83-3.22 in the AFINOS Study). Also, adolescents with medium
      and low levels of physical fitness had a higher risk of developing eating
      disorders (OR = 1.51, 95% CI: 1.05-2.16, and OR = 2.25, 95% CI: 1.60-3.19,
      respectively, in the AVENA Study, and OR = 1.73, 95% CI: 1.37-2.17, and OR = 4.11
      95% CI: 2.98-5.65, respectively, in the AFINOS Study) than adolescents with high
      levels of physical fitness. In both studies, the combined influence of overweight
      and physical fitness showed that adolescents with lower levels of physical
      fitness had an increased risk of developing eating disorders in both non
      overweight and overweight groups. CONCLUSIONS: Physical fitness might attenuate
      the influence of overweight on the development of eating disorders in
      adolescents.

PMID- 24449516
TI  - An integrated computational and experimental approach to gaining selectivity for
      MMP-2 within the gelatinase subfamily.
AB  - Looking for water-soluble inhibitors of matrix metalloproteinase-2 (MMP-2 or
      gelatinase A), we have previously reported compound 1, a potent MMP-2 inhibitor
      with a promising selectivity over the structurally homologous MMP-9 (gelatinase
      B). Here we report the results of Molecular Dynamics (MD) simulations for both
      gelatinases (MMP-2 and MMP-9), and for the corresponding MMP/1 complexes, in an
      attempt to shed light on the observed selectivity between the two enzymes. These
      studies indicated a higher plasticity of MMP-2 at the S1' pocket and suggested an
      induced-fit effect at the "back door" of this pocket. On the basis of these
      observations, we designed 11 a-d to aid further discrimination between MMP-2 and
      MMP-9. Those compounds displayed notably lower inhibitory activities against MMP
      9; in particular, 11 b proved to be over 100 times more active against MMP-2 than
      against MMP-9. MD simulations of the MMP/11 b complexes and thermodynamic
      integration calculations provided structural insight and relative binding
      energies consistent with the experimentally observed activity data. These
      findings demonstrate that structural differences in the S1' pocket bottom permit
      an improvement in selectivity in the inhibition of MMP-2 over that of MMP-9; this
      is of great relevance for future structure-based drug design because MMP-2 is a
      validated target for cancer therapy, whereas MMP-9 plays both detrimental and
      protective roles in cancer. This study also supports the need to consider the
      dynamics of the S1' pocket in order to achieve selectivity in the inhibition of
      MMPs.

PMID- 24449517
TI  - Resonance activation and collision-induced-dissociation of ions using rectangular
      wave dipolar potentials in a digital ion trap mass spectrometer.
AB  - Collision-induced dissociation (CID) of ions by resonance activation in a
      quadrupole ion trap is usually accomplished by resonance exciting the ions to
      higher kinetic energy, whereby the high kinetic energy ions collide with a bath
      gas, such as helium or argon, inside the trap and dissociate to fragments. A new
      ion activation method using a well-defined rectangular wave dipolar potential
      formed by dividing down the trapping rectangular waveform is developed and
      examined herein. The mass-selected parent ions are resonance excited to high
      kinetic energies by simply changing the frequency of the rectangular wave dipolar
      potential and dissociation proceeds. A relationship between the ion mass and the
      activation waveform frequency is also identified and described. This highly
      efficient (CID) procedure can be realized by simply changing the waveform
      frequency of the dipolar potential, which could certainly simplify tandem mass
      spectrometry analysis methods. 

PMID- 24449518
TI  - In vitro evaluation of Bacopa monniera extract and individual constituents on
      human recombinant monoamine oxidase enzymes.
AB  - Bacopa monniera is a traditional Ayurvedic medicinal plant that has been used
      worldwide for its nootropic action. Chemically standardized extract of B.
      monniera is now available as over the counter herbal remedy to enhance memory in
      children and adults. Considering the nootropic action of B. monniera, we
      evaluated the effect of clinically available B. monniera extract and six of B.
      monniera constituents (bacoside A3, bacopaside I, bacopaside II, bacosaponin C,
      bacosine, and bacoside A mixture) on recombinant human monoamine oxidase (MAO)
      enzymes. The effect of B. monniera extract and individual constituents on human
      recombinant MAO-A and MAO-B enzymes was evaluated using MAO-Glo(TM) assay kit
      (Promega Corporation, USA), following the instruction manual. IC50 and mode of
      inhibition were measured for MAO enzymes. Bacopaside I and bacoside A mixture
      inhibited the MAO-A and MAO-B enzymes. Bacopaside I exhibited mixed mode of
      inhibition with IC50 and Ki values of 17.08 +/- 1.64 and 42.5 +/- 3.53 ug/mL,
      respectively, for MAO-A enzyme. Bacopaside I is the major constituent of B.
      monniera, which inhibited the MAO-A enzyme selectively.

PMID- 24449519
TI  - Grief and major depression.

PMID- 24449520
TI  - MYC network mutations in high-risk chronic lymphocytic leukaemia.

PMID- 24449521
TI  - Percentage of pain intensity difference on an 11-point numerical rating scale
      underestimates acute pain resolution.
AB  - BACKGROUND: A 50% reduction in pain intensity difference (50%PID) between
      baseline and follow-up evaluation is commonly accepted as adequate pain relief in
      emergency departments (EDs). However, 50%PID seems to be problematic with the 11
      point numerical rating scale (NRS) since even baseline values are more divisible
      by 2 (50% reduction) than odd baseline values. This study evaluated the impact of
      this bias and integrated time between baseline and follow-up measurements,
      hypothesizing that the slope of relative pain intensity difference (SRPID) is a
      more accurate gauge of pain relief that can decrease bias and incorporate the
      time component of pain relief. METHODS: A post-hoc analysis of real-time data on
      an adult population from an urban ED identified 3199 consecutive patients who
      received an analgesic, had baseline NRS > 3 and a follow-up NRS within 2 h.
      Primary outcome was the percentage of patients with pain relieved from the 50%PID
      and the 50%SRPID criteria. RESULTS: Results showed that with 50%PID, even pain
      intensity levels on baseline NRS comprised a higher percentage of patients
      [60.7%; 95% confidence interval (CI): 58.8-63.0] with pain relief compared to odd
      pain intensity levels (51.7%; 95% CI: 48.8-54.6; p < 0.001), underestimating pain
      relieved patients by 9% [95% CI: 0.05-0.13; effect size (ES) = 0.09]. The
      percentage of pain-relieved subjects with the 50%SRPID criteria was not affected
      by baseline NRS values (59.7% for whole sample; 95% CI: 58.0-61.4; ES = 0.02).
      CONCLUSIONS: The 50%PID method with an 11-point NRS for assessing adequate pain
      relief is significantly biased for specific baseline pain intensity level. In the
      particular context of ED acute pain, the SRPID seems less biased.

PMID- 24449522
TI  - Organoplatinum-mediated synthesis of cyclic pi-conjugated molecules: towards a
      new era of three-dimensional aromatic compounds.
AB  - This article describes the most recent developments in the synthesis of three
      dimensional pi-conjugated molecules and the elucidation of their properties made
      by our research group. Various cycloparaphenylenes (CPPs) of different sizes and
      a cage-like 3D molecule were synthesized based on the platinum-mediated assembly
      of pi-units and subsequent reductive elimination of platinum. The assembly of pi
      units by this method mimics the self-assembly process for the formation of
      supramolecular ligand-metal complexes with 3D cages and polyhedral structures.
      Furthermore, reductive elimination of platinum successfully took place with high
      efficiency, despite the high strain energy of the target molecule. Several size
      dependent physical properties of CPPs, namely the photophysical, redox, and host
      guest chemistries, were also clarified. These results are of use for a molecular
      level understanding of CNT physical properties as well as fullerene peapods.
      Theoretical and electrochemical studies suggest that small CPPs and their
      derivatives should be excellent lead compounds for molecular electronics. 

PMID- 24449523
TI  - Enhanced photoelectrochemical water splitting efficiency of a hematite-ordered
      Sb:SnO2 host-guest system.
AB  - Host-guest systems such as hematite/SnO2 have attracted a great deal of interest
      as photoanodes for photoelectrochemical water splitting. In the present work we
      form an ordered porous tin oxide layer formed by self-organizing anodization of
      Sn films on a FTO substrate. Subsequently the anodic tin oxide nanostructure is
      doped with antimony (ATO) by a simple impregnation and annealing treatment, and
      then decorated with hematite using anodic deposition. Photoelectrochemical water
      splitting experiments show that compared to conventional SnO2 nanostructures,
      using a Sb doped nanochannel SnO2 as a host leads to a drastic increase of the
      water splitting photocurrent response up to 1.5 mA cm(-2) at 1.6 V (vs. RHE) in 1
      M KOH under AM 1.5 (100 mW cm(-2) ) conditions compared to 0.04 mA cm(-2) for the
      non-Sb doped SnO2 scaffold.

PMID- 24449524
TI  - Comparison of simulated cone beam computed tomography to conventional helical
      computed tomography for imaging of rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Cone beam computed tomography (CBCT) has emerged as a low
      radiation dose alternative to traditional computed tomography (CT) to evaluate
      the paranasal sinuses. The purpose of our study was to determine how often
      clinically important findings would be missed if CBCT was used routinely for
      sinus imaging. STUDY DESIGN: Retrospective review. METHODS: We evaluated all
      maxillofacial CT scans performed for sinusitis over a 1-year period. The original
      multidetector CT (MDCT) images were reviewed retrospectively. A theoretical CBCT
      was then created from the original study utilizing only the bone algorithm images
      and separately reviewed. We calculated the proportion of abnormal findings that
      were identified on the MDCT but would have been missed by the theoretical CBCT,
      and reviewed the medical record to determine which potentially missed findings
      would have changed management. Radiation dose from the MDCT scanners was
      calculated and compared to published dose estimates for the paranasal sinuses on
      CBCT. RESULTS: Maxillofacial CTs from 361 consecutive patients were included, of
      which 12 (3.3%) demonstrated findings that would have been missed on the
      theoretical CBCT. Of those, four (1.1%) would have resulted in a change in
      management. Effective radiation dose for our scanners ranged from 0.67 mSv to
      2.15 mSv, compared to a published estimated dose of 0.2 mSV for CBCT.
      CONCLUSIONS: In the majority of patients undergoing simulated CBCT for evaluation
      of sinusitis, incidental findings of soft-tissue disease were rare. With
      appropriate selection of patients, CBCT can offer substantial radiation dose
      reduction and may provide a viable alternative to standard MDCT sinus imaging
      protocols.

PMID- 24449525
TI  - Quantification of sweat gland volume and innervation in neuropathy: Correlation
      with thermoregulatory sweat testing.
AB  - INTRODUCTION: No study has correlated thermoregulatory sweat testing (TST) with
      histopathologic study of sweat glands (SGs) and SG nerve fibers (SGNFs). METHODS:
      We studied 10 neuropathy patients in whom anhidrosis was found by TST and 10
      matched controls. Skin biopsies were taken from both anhidrotic and sweating skin
      and immunohistochemical staining was done for nerves and basement membrane. For
      each biopsy, total tissue volume, total SG volume, and total SGNF length were
      measured. SGNF length per biopsy volume, SG volume per biopsy volume (SG%), and
      SGNF length per SG volume were calculated. RESULTS: SGNF length per biopsy volume
      was reduced in anhidrotic site biopsies of patients compared with controls. SG%
      was decreased and SGNF length per SG volume increased in patients compared with
      controls. CONCLUSIONS: The results suggest a concomitant loss of SG volume and
      SGNF length in neuropathy, with greater loss of SGNFs in anhidrotic skin,
      possibly exceeding collateral reinnervation.

PMID- 24449526
TI  - Morphological change of cell membrane by interaction with domain-swapped
      cytochrome c oligomers.
AB  - Monomeric cyt c has been reported to bind to the mitochondrial membrane by
      electrostatic and hydrophobic interactions with anionic phospholipids. We have
      previously shown that domain-swapped oligomeric cyt c retains the secondary
      structure of the monomer, and its surface possesses a larger area and more
      charges compared to the monomer. However, the effect of oligomerization of cyt c
      on cells has yet to be revealed. Herein, we investigated the interaction of
      oligomeric cyt c with anionic phospholipid-containing vesicles and the outer
      membrane of HeLa cells. Oligomeric cyt c interacted more strongly than monomeric
      cyt c with anionic phospholipid-containing vesicles and the outer membrane of
      HeLa cells. Oligomeric cyt c induced lateral phase separation of lipids in LUVs
      and GUVs, thereby leading to membrane disruption, whereas monomeric cyt c did
      not. Morphological changes in HeLa cells resulted from interaction with
      oligomeric cyt c, but little from interaction with the monomer. These results
      show that domain-swapped oligomeric proteins might exhibit properties different
      to those of monomer in cell systems. 

PMID- 24449527
TI  - The carrying pigeons of the cell: exosomes and their role in infectious diseases
      caused by human pathogens.
AB  - Exosomes have recently been classified as the newest family members of 'bioactive
      vesicles' that function to promote intercellular communication. Long ignored and
      thought to be only a mechanism by which cellular waste is removed, exosomes have
      garnered a huge amount of interest in recent years as their critical functions in
      maintaining homeostasis through intercellular communication and also in different
      types of diseases have been demonstrated. Many groundbreaking studies of exosome
      functions have been performed in the cancer field and the infectious disease
      areas of study, revealing the importance and also the fascinating complexity of
      exosomal packaging, targeting, and functions. Selective packaging of exosomes in
      response to the type of infection, exosomal modulation of the immune response and
      host signaling pathways, exosomal regulation of pathogen spread, and effects of
      exosomes on the degree of pathogenesis have all been well documented. In this
      review, we provide a synthesis of the current understanding of the role of
      exosomes during infections caused by human pathogens and discuss the implications
      of these findings for a better understanding of pathogenic mechanisms and future
      therapeutic and diagnostic applications. 

PMID- 24449528
TI  - Technologist viewpoint on PET/MR.

PMID- 24449529
TI  - A student's perspective on PET/MR: technologies can merge, but can technologists?

PMID- 24449530
TI  - Reflecting on our practice: an evaluation of Balint groups for medical students
      in psychiatry.
AB  - OBJECTIVE: This paper qualitatively evaluates a one-year trial of Balint clinical
      reflection groups for medical students in psychiatry at a large Australian
      tertiary referral hospital. The trial considered whether clinical reflection
      groups following the Balint process would be perceived as useful and relevant to
      the learning needs of the student participants. METHOD: A grounded theory
      approach was undertaken. This included survey data, thematic analysis of written
      feedback, and facilitator reflection on the process. Facilitators adapted the
      group process in response to participants' needs. These modifications included:
      increased education regarding the Balint process; the introduction of co
      presenters; and the inclusion of a didactic summary following each session.
      RESULTS: The evaluation suggested that fidelity of the Balint group experience
      was achieved and that student attitudes were neutral to mildly positive regarding
      the educational experience. CONCLUSIONS: Balint groups are potentially useful to
      medical students in the Australian context. We suggest that Balint groups may be
      more useful when applied in less alienating learning environments, such as during
      general practice rotations. Emphasis is placed on the need to maintain a dynamic
      approach by adapting the group and the educational processes as the work unfolds.

PMID- 24449531
TI  - The Sydney Mental Health Client Mortality Audit: what does it tell us and what
      are we to do?
AB  - OBJECTIVES: To examine the characteristics of those mental health clients of an
      Australian metropolitan health service who died during a 6 year period, 2005 -
      2010. METHODS: The medical records, and where available, coronial post-mortem
      examinations were audited for 109 people with schizophrenia who died while they
      were clients of the mental health service. RESULTS: The mean age of death for men
      was 45 years and for women, 47 years, compared to the general population's male
      and female life expectancy of 79 and 84 years, respectively. About one-half of
      the deaths were due to suicide (n = 55), followed by natural causes (n = 42;
      39%), undetermined causes (n = 7), and accidents or acts of violence (n = 5).
      Smoking rates, diagnosed diabetes and hypertension were higher in the group that
      died from natural causes. Morbid obesity (body mass index (BMI) > 35 kg/m(2))
      rates were higher in the group that died of natural causes (38%), compared with
      the suicide group (5%). CONCLUSIONS: While suicide accounts for the majority of
      those dying prematurely in this study cohort, it appears that for those who
      survive the risk of suicide in the earlier period of a chronic psychotic illness,
      there is yet another threat to life expectancy: death from preventable
      cardiorespiratory disorders, due to a poor lifestyle and social deprivation.

PMID- 24449533
TI  - Treatment of acute abdominal pain in the emergency room: a systematic review of
      the literature.
AB  - Appropriate pain therapy prior to diagnosis in patients with acute abdominal pain
      remains controversial. Several recent studies have demonstrated that pain therapy
      does not negatively influence either the diagnosis or subsequent treatment of
      these patients; however, current practice patterns continue to favour withholding
      pain medication prior to diagnosis and surgical treatment decision. A systematic
      review of PubMed, Web-of-Science and The-Cochrane-Library from 1929 to 2011 was
      carried out using the key words of 'acute', 'abdomen', 'pain', 'emergency' as
      well as different pain drugs in use, revealed 84 papers. The results of the
      literature review were incorporated into six sections to describe management of
      acute abdominal pain: (1) Physiology of Pain; (2) Common Aetiologies of Abdominal
      Pain; (3) Pre-diagnostic Analgesia; (4) Pain Therapy for Acute Abdominal Pain;
      (5) Analgesia for Acute Abdominal Pain in Special Patient Populations; and (6)
      Ethical and Medico-legal Considerations in Current Analgesia Practices. A
      comprehensive algorithm for analgesia for acute abdominal pain in the general
      adult population was developed. A review of the literature of common aetiologies
      and management of acute abdominal pain in the general adult population and
      special patient populations seen in the emergency room revealed that intravenous
      administration of paracetamol, dipyrone or piritramide are currently the
      analgesics of choice in this clinical setting. Combinations of non-opioids and
      opioids should be administered in patients with moderate, severe or extreme pain,
      adjusting the treatment on the basis of repeated pain assessment, which improves
      overall pain management. 

PMID- 24449534
TI  - Development of chiral catalysts for Mukaiyama aldol reactions in aqueous media.
AB  - Since the discovery of the Mukaiyama aldol reaction in 1973, tremendous efforts
      have been made to develop a definitive catalyst that catalyzes asymmetric
      Mukaiyama aldol reactions under mild conditions with broad substrate tolerance.
      Forty years later, an exhaustive search for a water-compatible Lewis acid was
      able to uncover the hidden potential of iron(II) and bismuth(III), leading to the
      establishment of broadly applicable and versatile catalytic systems for
      asymmetric Mukaiyama aldol reactions in aqueous media. The ternary catalytic
      system was able to expand the substrate generality considerably as the most
      distinguished catalyst ever reported. The superiority of this methodology over
      conventional methods has also been demonstrated in terms of high catalytic
      activity, simplicity of experimental procedures, and a wide substrate range
      including aqueous aldehydes, for which the stereochemistry had been regarded as
      difficult to control. Furthermore, a facile synthesis of the chiral ligand
      underscores its versatility. The reaction did not proceed at all without use of
      water. In the postulated mechanism, water plays prominent roles in: (1) producing
      the active metal complexes with a high water-exchange rate constant (3.2 * 10(6))
      to activate substrates effectively and to catalyze the reaction through a rapid
      proton transfer on the order of picoseconds; (2) facilitating the catalytic
      turnover with simultaneous desilylation as direct access to aldol adducts or
      facile recovery of active metal complexes; and (3) stabilizing rigid transition
      states composed of metal complexes and reactants through entropy-driven
      aggregation derived from the highest cohesive energy density.

PMID- 24449532
TI  - Time-dependent effects of isoflurane and dexmedetomidine on functional
      connectivity, spectral characteristics, and spatial distribution of spontaneous
      BOLD fluctuations.
AB  - Anesthesia is often necessary to perform fMRI experiments in the rodent model;
      however, commonly used anesthetic protocols may manifest changing brain
      conditions over the duration of the study. This possibility was explored in the
      current work. Eleven rats were anesthetized with 2% isoflurane anesthesia; four
      rats were anesthetized for a short period (30 min, simulating induction and fMRI
      setup) and seven rats were anesthetized for a long period (3 h, simulating
      surgical preparation). Following the initial anesthetic period, isoflurane was
      discontinued, and a dexmedetomidine bolus (0.025 mg/kg) and continuous
      subcutaneous infusion (0.05 mg/kg/h) were administered. Blood-oxygen-level
      dependent resting state imaging was performed every 30 min from 0.75 h post
      dexmedetomidine bolus until 5.75 h post-bolus. Evaluation of power spectra
      obtained from time courses in the primary somatosensory cortex revealed, in
      general, a monotonic increase in low-frequency power (0.05-0.3 Hz) in both groups
      over the duration of resting state imaging. Greater low-band spectral power (0.05
      0.15 Hz) is present in the short isoflurane group for the first 2.75 h, but the
      spectra become highly uniform at 3.25 h. The emergence of a ~0.18 Hz peak,
      beginning at the 3.75 h time point, exists in both groups and evolves similarly,
      increasing in strength as the duration of dexmedetomidine sedation (and time
      since isoflurane cessation) extends. In the long isoflurane group only, bilateral
      functional connectivity strengthens with anesthetic duration, and correlation is
      linearly linked to low-band spectral power. Convergence of connectivity and
      spectral metrics between the short and long isoflurane groups occurs at ~3.25 h,
      suggesting the effects of isoflurane have subsided. Researchers using
      dexmedetomidine following isoflurane for functional studies should be aware of
      the duration specific effects of the pre-scan isoflurane durations as well as the
      continuing influences of long-term imaging under dexmedetomidine.

PMID- 24449535
TI  - Biosourced nitrogen-doped microcellular carbon monoliths.
AB  - An original approach based on the hydrothermal carbonization of nitrogen
      containing biomass derivatives within the continuous phase of a direct
      concentrated emulsion is reported for the synthesis of nitrogen-doped
      microcellular carbon monoliths. These biosourced foams show promising
      performances as intrinsic electrocatalysts in the oxygen reduction reaction.
      Preliminary catalytic properties of powdered versus monolithic samples are
      discussed and suggest interesting prospects for their introduction within
      electrochemical devices. 

PMID- 24449536
TI  - Cementation: a hazardous event during joint arthroplasty surgery.

PMID- 24449537
TI  - The use of Nanotrap particles for biodefense and emerging infectious disease
      diagnostics.
AB  - Detection of early infectious disease may be challenging due to the low copy
      number of organisms present. To overcome this limitation and rapidly measure low
      concentrations of the pathogen, we developed a novel technology: Nanotrap
      particles, which are designed to capture, concentrate, and protect biomarkers
      from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that
      are capable of antigen capture through the coupling of affinity baits to the
      particles. Here, we describe recent findings demonstrating that Nanotrap
      particles are able to capture live infectious virus, viral RNA, and viral
      proteins. Capture is possible even in complex mixtures such as serum and allows
      the concentration and protection of these analytes, providing increased
      performance of downstream assays. The Nanotrap particles are a versatile sample
      preparation technology that has far reaching implications for biomarker discovery
      and diagnostic assays. 

PMID- 24449538
TI  - The hollow fiber bioreactor as a stroma-supported, serum-free ex vivo expansion
      platform for human umbilical cord blood cells.
AB  - The bone marrow microenvironment plays an integral role in the regulation of
      hematopoiesis. Residing stromal cells and the extracellular matrix in the bone
      marrow microenvironment provide biological signals that control hematopoietic
      stem cell (HSC) function. In this study, we developed a bio-mimetic co-culture
      platform using the hollow fiber bioreactor (HFBR) for ex vivo expansion of HSCs.
      We evaluated the efficacy of such a platform in comparison to standard cultures
      performed on tissue culture polystyrene (TCP), using a human stromal cell line
      (HS-5) as stromal support, co-cultured with lineage-depleted human cord blood
      cells in serum-free medium supplemented with a cytokine cocktail. Our results
      showed that the performance of the HFBR in supporting total cell and CD34(+)
      progenitor cell expansion was comparable to that of cultures on TCP. Cells
      harvested from the HFBR had a higher clonogenic ability. The performance of ex
      vivo-expanded cells from the HFBR in hematopoietic reconstitution in humanized
      mice was comparable to that of the TCP control. Scanning electron microscopy
      revealed that stroma cell growth inside the HFBR created a three-dimensional cell
      matrix architecture. These findings demonstrate the feasibility of utilizing the
      HFBR for creating a complex cell matrix architecture, which may provide good in
      vitro mimicry of the bone marrow, supporting large-scale expansion of HSCs. 

PMID- 24449539
TI  - Identification of fluorinases from Streptomyces sp MA37, Norcardia brasiliensis,
      and Actinoplanes sp N902-109 by genome mining.
AB  - The fluorinase is an enzyme that catalyses the combination of S-adenosyl-L
      methionine (SAM) and a fluoride ion to generate 5'-fluorodeoxy adenosine (FDA)
      and L-methionine through a nucleophilic substitution reaction with a fluoride ion
      as the nucleophile. It is the only native fluorination enzyme that has been
      characterised. The fluorinase was isolated in 2002 from Streptomyces cattleya,
      and, to date, this has been the only source of the fluorinase enzyme. Herein, we
      report three new fluorinase isolates that have been identified by genome mining.
      The novel fluorinases from Streptomyces sp. MA37, Nocardia brasiliensis, and an
      Actinoplanes sp. have high homology (80-87 % identity) to the original S.
      cattleya enzyme. They all possess a characteristic 21-residue loop. The three
      newly identified genes were overexpressed in E. coli and shown to be fluorination
      enzymes. An X-ray crystallographic study of the Streptomyces sp. MA37 enzyme
      demonstrated that it is almost identical in structure to the original fluorinase.
      Culturing of the Streptomyces sp. MA37 strain demonstrated that it not only also
      elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine, similar to
      S. cattleya, but this strain also produces a range of unidentified
      fluorometabolites. These are the first new fluorinases to be reported since the
      first isolate, over a decade ago, and their identification extends the range of
      fluorination genes available for fluorination biotechnology.

PMID- 24449540
TI  - Simultaneous determination of sulphoraphane and sulphoraphane nitrile in Brassica
      vegetables using ultra-performance liquid chromatography with tandem mass
      spectrometry.
AB  - INTRODUCTION: Several analytical methods exist for the determination of
      sulphoraphane or sulphoraphane nitrile from biological matrices and plant
      extracts. However, no UPLC-MS/MS method exists for the simultaneous detection of
      both. OBJECTIVE: To develop and validate an UPLC-MS/MS method for the
      simultaneous analysis of sulphoraphane and sulphoraphane nitrile from Brassica
      oleracea L. ssp. italica METHODS: This method was developed utilising an Acquity
      BEH C8 column with gradient elution combined with tandem mass spectrometry, using
      positive electrospray ionisation in multiple reaction monitoring mode. RESULTS:
      The retention times for sulphoraphane and sulphoraphane nitrile were 0.4 and 0.6
      min respectively, and total run time was 3 min. The method was validated for
      linearity, sensitivity, precision, accuracy, matrix effects and recovery. The
      method was employed to determine glucoraphanin hydrolysis products in broccoli
      and the predominant product was found to vary depending on the variety tested. It
      was also applied to the accurate determination of sulphoraphane and sulphoraphane
      nitrile in broccoli samples hydrolysed under different conditions. It was
      observed that the formation of sulphoraphane and sulphoraphane nitrile was
      influenced by the temperature of the reaction. CONCLUSION: The validated UPLC
      MS/MS method for simultaneous detection of sulphoraphane and sulphoraphane
      nitrile was shown to be applicable to broccoli plants and is expected to be
      applicable to other cruciferous sources.

PMID- 24449541
TI  - Comparative study of the methodology used in the extraction of isoflavones from
      legumes applying a modified QuEChERS approach.
AB  - INTRODUCTION: Isoflavones are phytochemicals of great interest because of their
      association with a large variety of positive effects on human health. The major
      sources of isoflavones in the diet are plants of the Leguminosae family,
      especially soybeans, although many other legumes more widely consumed in the
      Mediterranean diet have also been reported to contain these compounds. In
      previous work we extracted isoflavones from samples using a modified QuEChERS
      (Quick Easy Cheap Effective Rugged Safe) methodology. OBJECTIVE: To compare
      different methods for placing the sample and the solvent in contact to optimise
      the extraction of isoflavones from legumes (chickpeas, lentils and white beans)
      using a modified QuEChERS methodology. METHOD: Five different approaches to
      sample agitation were tested: vortex agitation, thermostatted stirring agitation
      and thermostatted tray shaking, and a thermostatted ultrasound bath and an
      ultrasound probe. To evaluate the different methodologies a modified QuEChERS
      approach was used as the extraction method. The separation and quantification of
      isoflavones was carried out using liquid chromatography-triple quadrupole/mass
      spectrometry (LC-MS/MS). RESULTS: The best methods were found upon using a
      thermostatted shaking tray for the extraction of chickpeas and white beans and
      the ultrasound probe for lentil samples. These methods were chosen based on the
      highest amount of analytes obtained as well as the best recovery values.
      CONCLUSION: Determination of isoflavones in foods may be affected by the
      different methods used to place the sample and the solvent in contact in the
      extraction step. The main advantages of the proposed extraction procedures are
      their simplicity, speed, reliability and low cost.

PMID- 24449544
TI  - Prospects for multimodality imaging in peripheral artery disease.

PMID- 24449545
TI  - PFO or UFO: how good is transesophageal echocardiography in identifying patent
      foramen ovale as the cause of a cryptogenic stroke?

PMID- 24449546
TI  - Symptoms in patients with severe aortic stenosis and preserved left ventricular
      ejection fraction: is it all about diastole?

PMID- 24449547
TI  - Imaging for preintervention planning: transcatheter pulmonary valve therapy.

PMID- 24449549
TI  - Is MRI the preferred method for evaluating right ventricular size and function in
      patients with congenital heart disease?: MRI is not the preferred method for
      evaluating right ventricular size and function in patients with congenital heart
      disease.

PMID- 24449548
TI  - Is MRI the preferred method for evaluating right ventricular size and function in
      patients with congenital heart disease?: MRI is the preferred method for
      evaluating right ventricular size and function in patients with congenital heart
      disease.

PMID- 24449550
TI  - Successful diagnosis of an atypical prosthetic vascular graft infection without
      perivascular abscess: luminal vegetation as the hidden septic source.

PMID- 24449551
TI  - Letter by House et al regarding article, "Prosthesis-patient mismatch in bovine
      pericardial aortic valves: evaluation using 3 different modalities and associated
      medium-term outcomes".

PMID- 24449552
TI  - Response to letter regarding article, "Prosthesis-patient mismatch in bovine
      pericardial aortic valves: evaluation using 3 different modalities and associated
      medium-term outcomes".

PMID- 24449553
TI  - Letter by Martin and Jenni regarding article, "Limitations of Doppler
      echocardiography in the evaluation of serial stenoses".

PMID- 24449554
TI  - Response to letter regarding article, "Limitations of Doppler echocardiography in
      the evaluation of serial stenoses".

PMID- 24449555
TI  - Letter by Girdauskas regarding article, "Aortic dilation in bicuspid aortic valve
      disease: flow pattern is a major contributor and differs with valve fusion type".

PMID- 24449556
TI  - Response to letter regarding article, "Aortic dilation in bicuspid aortic valve
      disease: flow pattern is a major contributor and differs with valve fusion type".

PMID- 24449557
TI  - Letter by Di Bella et al regarding article, "Effect of combined systolic and
      diastolic functional parameter assessment for differentiation of cardiac
      amyloidosis from other causes of concentric left ventricular hypertrophy".

PMID- 24449558
TI  - Comparing Visible and Invisible Social Support: Non-evaluative Support Buffers
      Cardiovascular Responses to Stress.
AB  - Previous research suggests that in contrast to invisible social support, visible
      social support produces exaggerated negative emotional responses. Drawing on work
      by Bolger and colleagues, this study disentangled social support visibility from
      negative social evaluation in an examination of the effects of social support on
      negative emotions and cardiovascular responses. As part of an anticipatory speech
      task, 73 female participants were randomly assigned to receive no social support,
      invisible social support, non-confounded visible social support or visible social
      support as delivered in a 2007 study by Bolger and Amarel. Twelve readings, each
      for systolic blood pressure, diastolic blood pressure and heart rate were taken
      at 5-min intervals throughout the periods of baseline, reactivity and recovery.
      Cardiovascular outcomes were tested by incorporating a series of theoretically
      driven planned contrasts into tests of stress reactivity conducted through
      piecewise growth curve modelling. Linear and quadratic trends established
      cardiovascular reactivity to the task. Further, in comparison to the control and
      replication conditions, the non-confounded visible and invisible social support
      conditions attenuated cardiovascular reactivity over time. Pre- and post-speech
      negative emotional responses were not affected by the social support
      manipulations. These results suggest that appropriately delivered visible social
      support may be as beneficial as invisible social support.

PMID- 24449559
TI  - Re: TG13 antimicrobial therapy for acute cholangitis and cholecystitis.

PMID- 24449560
TI  - Response to re: TG13 antimicrobial therapy for acute cholangitis and
      cholecystitis.

PMID- 24449561
TI  - Enzymatic hydration activity assessed by selective spectrophotometric detection
      of alcohols: a novel screening assay using oleate hydratase as a model enzyme.
AB  - Hydroxy fatty acids (HFAs) are high-added-value compounds, which are incorporated
      in polymers, lubricants, emulsifiers and stabilizers and have potential medicinal
      use. In nature, HFAs are regio-specifically synthesized by several enzymes,
      including P450 monooxygenases, lipoxygenases, hydratases, 12-hydroxylases, and
      diol synthases. The growing demand for HFAs warrants the development of simple
      and efficient analytical methods that enable high-throughput detection of the
      hydroxylated product in the presence of its unsaturated precursor. Herein a novel
      high-throughput assay for the detection of alcohols is described using oleate
      hydratase (OHase, EC 4.2.1.53) from Elizabethkingia meningoseptica as the model
      enzyme. The developed assay is based on the selective spectrophotometric
      detection of alkyl nitrites formed upon the reaction between the hydroxyl group
      and nitrous acid. The assay proved to discriminate between unsaturated fatty
      acids as well as small cyclic and acyclic unsaturated alkenes and their
      corresponding alcohols. Lower detection limits were 1.5-3 mM with excellent Z'
      factors. Enzymatic reactions using OHase with oleic acid resulted in somewhat
      lower Z-factors for various enzyme preparations. This small scale assay can
      enable fast discovery of new microorganisms or improved enzymes from mutant
      libraries and will be useful for biocatalytic strategies involving fatty acid
      (de)hydrating enzymes. 

PMID- 24449562
TI  - Efficient inactivation of Burkholderia pseudomallei or Francisella tularensis in
      infected cells for safe removal from biosafety level 3 containment laboratories.
AB  - Working with infectious agents that require BSL-3 level containment agents offers
      many challenges for researchers. BSL-3 containment laboratories are usually not
      equipped with expensive specialty equipment that is needed for studies such as
      flow cytometric analysis, microscopy, and proteomic analyses. Therefore, for most
      researchers that are working with BSL-3 level infectious agents, removal of
      samples from BSL-3 laboratories for these types of studies is necessary, and
      methods for complete and dependable inactivation of the samples are required. In
      this report, we have carried out a thorough characterization of the effectiveness
      of paraformaldehyde fixation for inactivation of cell samples infected with the
      intracellular bacterial agents Burkholderia pseudomallei (Bp) and Francisella
      tularensis (Ft), both of which are Tier 1 select agent pathogens that require BSL
      3 containment. We have demonstrated that cells infected with these pathogens are
      completely inactivated via 5-min treatment with 4% paraformaldehyde. Moreover, a
      15-min treatment with 2% paraformaldehyde completely sterilized both Bp- and Ft
      infected cells. These studies also revealed that Bp is significantly more
      sensitive to paraformaldehyde treatment than Ft. Our findings have clearly
      demonstrated that a 15-min treatment of Bp- or Ft-infected cells with 4%
      paraformaldehyde solution will allow for safe removal of the cell samples from
      BSL-3 laboratories for downstream studies. 

PMID- 24449563
TI  - Metabolism of TM-2, a potential antitumor drug, in rats by using LC-MS.
AB  - TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-beta-diacetoxy-2-alpha-benzoyloxy-5
      beta-20-epoxy-1,13-alpha-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a
      novel semisynthetic taxane derivative. Our previous study suggested that TM-2 is
      a promising antitumor analogue. In this paper, the metabolism of TM-2 was
      investigated in rats following intravenous administration. Two different types of
      mass spectrometry-hybrid linear trap quadrupole orbitrap (LTQ-Orbitrap) mass
      spectrometry and triple-quadrupole tandem (QQQ) mass spectrometry-were employed
      to acquire structural information of TM-2 metabolites. A total of 17 components
      were identified as the metabolites of TM-2 in bile, feces, and urine samples.
      Accurate mass measurement using LC-LTQ-Orbitrap-MS was used to determine the
      accurate mass data and elemental composition of metabolites thereby confirming
      the proposed structures of the metabolites. The metabolites proposed were mainly
      oxidates of TM-2, including methoxy, hydroxyl, dihydroxy, and trihydroxyl
      analogues. The major metabolic pathway of TM-2 was the hydroxylation of the
      taxane ring or the lateral chain. These important metabolic data serve as a
      useful resource to support further research of TM-2. 

PMID- 24449564
TI  - Red fluorescent turn-on ligands for imaging and quantifying G protein-coupled
      receptors in living cells.
AB  - Classical fluorescence-based approaches to monitor ligand-protein interactions
      are generally hampered by the background signal of unbound ligand, which must be
      removed by tedious washing steps. To overcome this major limitation, we report
      here the first red fluorescent turn-on probes for a G protein-coupled receptor
      (oxytocin receptor) at the surface of living cells. The peptide ligand carbetocin
      was conjugated to one of the best solvatochromic (fluorogenic) dyes, Nile Red,
      which turns on emission when reaching the hydrophobic environment of the
      receptor. We showed that the incorporation of hydrophilic octa(ethylene glycol)
      linker between the pharmacophore and the dye minimized nonspecific interaction of
      the probe with serum proteins and lipid membranes, thus ensuring receptor
      specific turn-on response. The new ligand was successfully applied for background
      free imaging and quantification of oxytocin receptors in living cells.

PMID- 24449565
TI  - Underdiagnosis of depression in young people.

PMID- 24449569
TI  - Editorial: B cells: not just making immunoglobulin anymore.

PMID- 24449570
TI  - Editorial: systemic lupus erythematosus: death by fire and ICE?

PMID- 24449571
TI  - Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium.
AB  - OBJECTIVE: To investigate the global molecular effects of tocilizumab (TCZ) in
      comparison with methotrexate (MTX) treatment in synovial biopsy tissue obtained
      from patients with previously untreated rheumatoid arthritis (RA) before therapy
      (T0) and 12 weeks after the initiation of therapy (T12), and to compare the
      results with previous gene expression data obtained in synovial biopsy tissue
      from adalimumab (ADA)- and rituximab (RTX)-treated patients with RA. METHODS:
      Paired synovial biopsy samples were obtained at T0 and T12 from the affected knee
      of TCZ-treated RA patients and MTX-treated RA patients. Gene expression studies
      were performed using GeneChip Human Genome U133 Plus 2.0 microarrays, and
      confirmatory quantitative real-time reverse transcription-polymerase chain
      reaction experiments were performed on selected transcripts. The effects of TCZ
      and MTX on synovial cell populations and histologic characteristics were assessed
      by immunohistochemistry. RESULTS: Gene expression studies showed that blockade of
      the interleukin-6 receptor (IL-6R) gene (IL6R) using TCZ induced a significant
      decrease in the expression of numerous chemokine and T cell activation genes in
      the RA synovium. These effects strongly correlated with the molecular effects of
      MTX and RTX therapy on RA synovial tissue, but differed from the molecular
      changes induced by ADA (decreased expression of genes involved in cell
      proliferation). CONCLUSION: The molecular similarities between the effects of
      TCZ, RTX, and MTX therapies in the RA synovium indicate that B cell- and IL-6
      dependent pathways play synergistic roles in the pathogenesis of the disease, in
      particular through activation of T cell responses. Moreover, these results open
      perspectives for the individualization of therapeutic decisions, based on a
      better knowledge of the synovial molecular effects of each type of RA therapy.

PMID- 24449572
TI  - Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an
      extended UK genome-wide association study.
AB  - OBJECTIVE: The number of confirmed rheumatoid arthritis (RA) loci currently
      stands at 32, but many lines of evidence indicate that expansion of existing
      genome-wide association studies (GWAS) enhances the power to detect additional
      loci. This study was undertaken to extend our previous RA GWAS in a UK cohort,
      adding more independent RA cases and healthy controls, with the aim of detecting
      novel association signals for susceptibility to RA in a homogeneous UK cohort.
      METHODS: A total of 3,223 UK RA cases and 5,272 UK controls were available for
      association analyses, with the extension adding 1,361 cases and 2,334 controls to
      the original GWAS data set. The genotype data for all RA cases were imputed using
      the Impute program version 2. After stringent quality control thresholds were
      applied, 3,034 cases and 5,271 controls (1,831,729 single-nucleotide
      polymorphisms [SNPs]) were available for analysis. Association testing was
      performed using Plink software. RESULTS: The analyses indicated a suggestive
      association with susceptibility to RA (P < 0.0001) for 6 novel RA loci that have
      been previously found to be associated with other autoimmune diseases; these 6
      SNPs were genotyped in independent samples. Two of the associated loci were
      validated, one of which was associated with RA at genome-wide levels of
      significance in the combined analysis, identifying a novel RA locus at 22q12 (P =
      6.9 * 10(-9) ). In addition, most of the previously known RA susceptibility loci
      were confirmed to be associated with RA, and for 16 of the loci, the strength of
      the association was increased. CONCLUSION: This study identified a new RA locus
      mapping to 22q12. These results support the notion that increasing the power of
      GWAS enhances novel gene discovery.

PMID- 24449573
TI  - Structural changes and antibody enrichment in the lungs are early features of
      anti-citrullinated protein antibody-positive rheumatoid arthritis.
AB  - OBJECTIVE: It has been suggested that immunologic events in the lungs may be
      involved in triggering immunity, in particular production of anti-citrullinated
      protein antibodies (ACPAs) during early phases of rheumatoid arthritis (RA). The
      aim of this study was to investigate the structural and immunologic features of
      the lungs in incident cases of early RA in relation to ACPA presence and smoking
      status. METHODS: High-resolution computed tomography (HRCT) was used to examine
      the lungs of 105 patients with early, untreated RA (70 with ACPA-positive RA and
      35 with ACPA-negative RA) and 43 healthy individuals. Bronchoscopy with
      collection of bronchoalveolar lavage (BAL) fluid and mucosal bronchial biopsy
      specimens was performed in 23 RA patients. The presence of citrullinated proteins
      in the bronchial tissue was detected by immunohistochemical staining. ACPAs
      (detected with an anti-cyclic citrullinated peptide 2 test) and total Ig levels
      were determined in the sera and BAL fluid of RA patients. RESULTS: HRCT imaging
      revealed that 63% of ACPA-positive RA patients had parenchymal lung
      abnormalities, compared with only 37% of ACPA-negative RA patients and 30% of
      healthy controls (each P < 0.05). These significant differences remained after
      adjustment for smoking status. Airway changes detected by HRCT were more frequent
      in RA patients than in healthy controls (66% versus 42%; P < 0.05), but there was
      no difference between ACPA-positive and ACPA-negative RA patients.
      Immunohistochemical studies of the bronchial tissue showed increased staining for
      citrullinated proteins in ACPA-positive RA patients compared with ACPA-negative
      RA patients (P < 0.05). ACPA levels were relatively higher in the BAL fluid as
      compared with the sera of ACPA-positive RA patients, suggesting that there is
      local production of ACPAs in the lungs of these patients. CONCLUSION: The
      presence of ACPAs is associated with parenchymal lung abnormalities, site
      specific citrullination, and antibody enrichment in the lungs early in the
      development of ACPA-positive RA.

PMID- 24449574
TI  - Dual role of autophagy in stress-induced cell death in rheumatoid arthritis
      synovial fibroblasts.
AB  - OBJECTIVE: To investigate the role of autophagy in the regulation of cell death
      in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: RASFs and
      osteoarthritis synovial fibroblasts (OASFs) were treated with thapsigargin (TG),
      an inducer of endoplasmic reticulum (ER) stress, and MG132, a proteasome
      inhibitor. Then, 3-methyladenine was used as an autophagy inhibitor and
      bafilomycin A1 as a lysosome inhibitor. Polyubiquitinated proteins, p62, and
      autophagy induction were evaluated by immunoblotting, immunofluorescence
      microscopy, and immunohistochemistry, respectively. OASFs were transfected with
      small interfering RNA targeting autophagy-linked FYVE protein (ALFY). Cell death
      was evaluated by flow cytometry and a caspase 3 activity assay. RESULTS: In
      RASFs, the induction of autophagy by TG and MG132 was increased compared to that
      in OASFs. Whereas autophagy promoted a caspase 3-independent induction of cell
      death under ER stress, autophagy had a protective role in apoptosis induced by
      proteasome inhibition. Treatment of RASFs with 3-methyladenine blocked TG-induced
      cell death. ER stress induced a strong accumulation of p62-positive
      polyubiquitinated protein aggregates, accompanied by the formation of large
      vacuoles in RASFs but not OASFs. Furthermore, TG-induced p62 protein expression
      was increased, whereas TG-induced ALFY expression was reduced, in RASFs compared
      to OASFs. ALFY knockdown promoted the accumulation of p62, the formation of
      polyubiquitinated protein aggregates, and cell death. CONCLUSION: Our data
      provide the first evidence of a dual role of autophagy in the regulation of death
      pathways in RASFs. A reduced expression of ALFY and the formation of p62-positive
      polyubiquitinated protein aggregates promote cell death in RASFs under severe ER
      stress.

PMID- 24449575
TI  - A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in
      rheumatoid arthritis.
AB  - OBJECTIVE: We previously showed that Cyr61 acts to promote fibroblast-like
      synoviocyte (FLS) proliferation and Th17 cell differentiation, suggesting that
      Cyr61 plays an important role in mediating the joint inflammation and damage in
      rheumatoid arthritis (RA). The aim of this study was to investigate whether Cyr61
      expression is regulated at the posttranscription level, and if so, how this
      regulation connects to other etiologic factors in RA. METHODS: Expression of
      microRNA-22 (miR-22) in synovial tissue was detected by real-time polymerase
      chain reaction (PCR) using miRNA-specific TaqMan MGB probes. MicroRNA-22 promoter
      activity was analyzed using a Dual-Luciferase Reporter Assay. Cytokine expression
      was measured by enzyme-linked immunosorbent assay, and the expression of other
      factors was measured by real-time PCR or Western blotting. RESULTS: MicroRNA-22
      directly targeted the 3'-untranslated region of Cyr61 messenger RNA and inhibited
      Cyr61 expression. Expression of miR-22 was down-regulated and was negatively
      correlated with Cyr61 expression in RA synovial tissue. Furthermore, wild-type
      p53 activated miR-22 transcription by binding to the promoter region of the miR
      22 gene, while the mutant forms of p53 frequently found in RA synovial tissue
      were shown to have lost the ability to activate miR-22 expression. As a result,
      miR-22 was down-regulated, contributing to the overexpression of Cyr61 in RA FLS.
      CONCLUSION: Our results not only reveal a novel mechanism whereby p53 is involved
      in the posttranscriptional regulation of Cyr61 expression via miRNA-22, but also
      provide a molecular explanation for the role of somatic mutations of p53, which
      are frequently observed in RA synovial tissue, in the etiology of this autoimmune
      disease.

PMID- 24449576
TI  - B cell-specific expression of inducible costimulator ligand is necessary for the
      induction of arthritis in mice.
AB  - OBJECTIVE: Inducible costimulator (ICOS)-ICOSL interactions are necessary for
      activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed
      on B cells, macrophages, and dendritic cells and can be induced on
      nonhematopoietic cells. The aim of this study was to determine whether expression
      of ICOSL on B cells is necessary for the development of proteoglycan (PG)-induced
      arthritis (PGIA). METHODS: PGIA was initiated by immunizing wild-type and ICOSL
      deficient (ICOSL(-/-) ) or B cell-specific ICOSL(-/-) chimeric BALB/c mice with
      human PG in adjuvant. The onset and severity of arthritis were monitored over
      time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured
      in vitro after the cells were restimulated with PG. Germinal center (GC) B cells,
      plasma cells, Tfh cells, and Treg cells were identified by staining with specific
      antibodies. RESULTS: Arthritis progression was completely inhibited in both
      ICOSL(-/-) mice and B cell-specific ICOSL(-/-) chimeric mice. Production of the
      Teff cell-produced cytokines interferon-gamma and interleukin-17 (IL-17) and the
      antiinflammatory cytokine IL-4 was suppressed. The reduced percentages of GCs and
      Tfh cells and the decreased production of IL-21 correlated with a decrease in the
      anti-mouse PG antibody response. However, the percentage of plasma cells was not
      reduced despite a reduction in IgG responses. CONCLUSION: These data indicate
      that the signals provided by ICOSL-expressing B cells to Teff cells and Tfh cells
      are necessary for the development of arthritis. Thus, therapeutic blockade of
      ICOSL-ICOS interactions may be an effective strategy for the treatment of
      rheumatoid arthritis.

PMID- 24449578
TI  - A global increase in 5-hydroxymethylcytosine levels marks osteoarthritic
      chondrocytes.
AB  - OBJECTIVE: To investigate the role of the newly discovered epigenetic mark 5
      hydroxymethylcytosine (5hmC) and its regulators in altered gene expression in
      osteoarthritis (OA). METHODS: Cartilage was obtained from OA patients undergoing
      total knee arthroplasty and from control patients undergoing anterior cruciate
      ligament reconstruction. Global levels of 5hmC and 5-methylcytosine (5mC) were
      investigated using immunoblotting, enzyme-linked immunosorbent assays, and
      cellular staining. Gene expression changes were monitored by quantitative
      polymerase chain reaction (PCR) analysis. Levels of locus-specific 5hmC and 5mC
      at CpG sites in the matrix metalloproteinase 1 (MMP-1), MMP-3, ADAMTS-5, and
      hypoxanthine guanine phosphoribosyltransferase 1 (HPRT-1) promoters were
      quantified using a glucosylation and enzyme digestion-based method followed by
      quantitative PCR analysis. Global and locus-specific 5hmC levels and gene
      expression changes were monitored in normal chondrocytes stimulated with
      inflammatory cytokines to identify the effect of joint inflammation. RESULTS: A
      global 5-6-fold increase in 5hmC concomitant with a loss of TET1 was observed in
      human OA chondrocytes compared to normal chondrocytes. Enrichment of 5hmC was
      observed in promoters of enzymes critical to OA pathology, MMP-1 and MMP-3. Short
      term treatment of normal chondrocytes with inflammatory cytokines induced a rapid
      decrease in TET1 expression but no global or locus-specific 5hmC enrichment.
      CONCLUSION: This study provides the first evidence of an epigenetic imbalance of
      the 5hmC homeostasis in OA leading to TET1 down-regulation and 5hmC accumulation.
      Our experiments identify 5hmC and its regulators as potential diagnostic and
      therapeutic targets in OA.

PMID- 24449577
TI  - Protective effects of C-type natriuretic peptide on linear growth and articular
      cartilage integrity in a mouse model of inflammatory arthritis.
AB  - OBJECTIVE: The C-type natriuretic peptide (CNP) signaling pathway is a major
      contributor to postnatal skeletal growth in humans. This study was undertaken to
      investigate whether CNP signaling could prevent growth delay and cartilage damage
      in an animal model of inflammatory arthritis. METHODS: We generated transgenic
      mice that overexpress CNP (B6.SJL-Col2a1-NPPC) in chondrocytes. We introduced the
      CNP transgene into mice with experimental systemic inflammatory arthritis (K/BxN
      T cell receptor [TCR]) and determined the effect of CNP overexpression in
      chondrocytes on the severity of arthritis, cartilage damage, and linear growth.
      We also examined primary chondrocyte cultures for changes in gene and protein
      expression resulting from CNP overexpression. RESULTS: K/BxN TCR mice exhibited
      linear growth delay (P < 0.01) compared to controls, and this growth delay was
      correlated with the severity of arthritis. Diminished chondrocyte proliferation
      and matrix production was also seen in K/BxN TCR mice. Compared to non-CNP
      transgenic mice, K/BxN TCR mice with overexpressed CNP had milder arthritis, no
      growth delay, and less cartilage damage. Primary chondrocytes from mice
      overexpressing CNP were less sensitive to inflammatory cytokines than wild-type
      mouse chondrocytes. CONCLUSION: CNP overexpression in chondrocytes can prevent
      endochondral growth delay and protect against cartilage damage in a mouse model
      of inflammatory arthritis. Pharmacologic or biologic modulation of the CNP
      signaling pathway may prevent growth retardation and protect cartilage in
      patients with inflammatory joint diseases, such as juvenile idiopathic arthritis.

PMID- 24449579
TI  - Brief report: carboxypeptidase B serves as a protective mediator in
      osteoarthritis.
AB  - OBJECTIVE: We previously demonstrated that carboxypeptidase B (CPB) protects
      against joint erosion in rheumatoid arthritis by inactivating complement
      component C5a. We also found that levels of CPB are abnormally high in the
      synovial fluid of individuals with another joint disease, osteoarthritis (OA). We
      undertook this study to investigate whether CPB plays a role in the pathogenesis
      of OA. METHODS: We compared the development of OA in CPB-deficient (Cpb2(-/-) )
      mice and wild-type mice by subjecting them to medial meniscectomy and
      histologically assessing cartilage damage, osteophyte formation, and synovitis in
      the stifle joints 4 months later. We measured levels of proCPB, proinflammatory
      cytokines, and complement components in synovial fluid samples from patients with
      symptomatic and radiographic knee OA. Finally, we used enzyme-linked
      immunosorbent assay, flow cytometry, and hemolytic assays to assess the effect of
      CPB on formation of membrane attack complex (MAC)-a complement effector critical
      to OA pathogenesis. RESULTS: Cpb2(-/-) mice developed dramatically greater
      cartilage damage than did wild-type mice (P < 0.01) and had a greater number of
      osteophytes (P < 0.05) and a greater degree of synovitis (P < 0.05). In synovial
      fluid samples from OA patients, high levels of proCPB were associated with high
      levels of proinflammatory cytokines and complement components, and levels of
      proCPB correlated positively with those of MAC. In in vitro complement activation
      assays, activated CPB suppressed the formation of MAC as well as MAC-induced
      hemolysis. CONCLUSION: Our data suggest that CPB protects against inflammatory
      destruction of the joints in OA, at least in part by inhibiting complement
      activation.

PMID- 24449580
TI  - A panel of biomarkers is associated with increased risk of the presence and
      progression of atherosclerosis in women with systemic lupus erythematosus.
AB  - OBJECTIVE: An increased frequency of atherosclerosis (ATH) in systemic lupus
      erythematosus (SLE) is well-documented but not fully explained by the presence of
      traditional cardiac risk factors. Several nontraditional biomarkers, including
      proinflammatory high-density lipoprotein (piHDL) and leptin, have been
      individually associated with subclinical ATH in SLE. The aim of this study was to
      examine whether these and other biomarkers can be combined into a risk profile,
      the Predictors of Risk for Elevated Flares, Damage Progression, and Increased
      Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to
      better predict future progression of ATH. METHODS: In total, 210 patients with
      SLE and 100 age-matched healthy control subjects (all women) participated in this
      prospective cohort study. The longitudinal presence of carotid plaque and intima
      media thickness (IMT) were measured at baseline and followup (mean +/- SD 29.6 +/
      9.7 months). RESULTS: At followup, carotid plaque was present in 29% of SLE
      patients. Factors significantly associated with plaque, determined using Salford
      Predictive Modeling and multivariate analysis, included age >=48 years (odds
      ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin
      levels >=34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels >=373 pg/ml
      (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine
      levels >=12 MUmoles/liter were also a predictor. However, no single variable
      demonstrated an ideal combination of good negative predictive values (NPVs),
      positive predictive values (PPVs), sensitivity, and specificity. A high-risk
      PREDICTS profile was defined as >=3 positive biomarkers or >=1 positive biomarker
      plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was
      94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE
      patients with the high-risk profile had 28-fold increased odds for the
      longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P <
      0.001). CONCLUSION: A high-risk PREDICTS score confers 28-fold increased odds of
      the presence of any current, progressive, or acquired carotid plaque, both in
      patients with SLE and in control subjects, and is significantly associated with
      higher rates of IMT progression.

PMID- 24449581
TI  - Toll-like receptor 7-stimulated tumor necrosis factor alpha causes bone marrow
      damage in systemic lupus erythematosus.
AB  - OBJECTIVE: To define the pathogenesis of bone marrow (BM) involvement in systemic
      lupus erythematosus (SLE). METHODS: Tumor necrosis factor alpha (TNFalpha)
      levels, cell death, and cellular damage in BM from SLE patients, controls, and
      mice with pristane-induced lupus were analyzed using a morphometric technique and
      immunohistochemistry. The pathogenesis of BM abnormalities was studied in wild
      type (WT), TNFalpha(-/-) , Toll-like receptor-deficient (TLR-7(-/-) ), interferon
      (IFN)-alpha/beta/omega receptor-knockout (IFNAR(-/-) ), and B cell-deficient
      (MUmt) mice treated with pristane. Flow cytometry was used to examine TNFalpha
      production (by intracellular staining) and plasma cell/plasmablast development.
      CXCL12 expression was determined by quantitative polymerase chain reaction.
      RESULTS: BM from SLE patients exhibited striking death of niche and hematopoietic
      cells associated with TNFalpha overproduction. BM from mice with a type I IFN
      mediated lupus syndrome induced by pristane showed similar abnormalities.
      TNFalpha was produced mainly by BM neutrophils, many with phagocytosed nuclear
      material (lupus erythematosus cells). TNFalpha production was abolished in
      pristane-treated TLR-7(-/-) and MUmt mice but was restored in MUmt mice by
      infusing normal plasma. Pristane-treated WT and IFNAR(-/-) mice developed anemia,
      BM hypocellularity, and extramedullary hematopoiesis, which were absent in TLR-7(
      /-) and TNFalpha(-/-) mice. Additionally, the expression of CXCL12, which is
      produced by stromal cells and mediates homing of hematopoietic cells and
      plasmablasts, was decreased in BM from pristane-treated WT mice but was normal in
      BM from pristane-treated TNFalpha(-/-) mice. CONCLUSION: Although autoantibodies
      and glomerulonephritis are type I IFN dependent, lupus-associated BM
      abnormalities were TLR-7 and TNFalpha driven but type I IFN independent,
      suggesting that lupus is a disorder of innate immunity in which TLR-7 activation
      by phagocytosed nuclei causes relentless type I IFN and TNFalpha production
      mediating glomerulonephritis and hematologic involvement, respectively.

PMID- 24449582
TI  - An essential role of caspase 1 in the induction of murine lupus and its
      associated vascular damage.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome
      associated with organ damage and an elevated risk of cardiovascular disease
      resulting from activation of both innate and adaptive immune pathways. Recently,
      increased activation of the inflammasome machinery in SLE has been described.
      Using the mouse model of pristane-induced lupus, we undertook this study to
      explore whether caspase 1, the central enzyme of the inflammasome, plays a role
      in the development of SLE and its associated vascular dysfunction. METHODS: Eight
      week-old wild-type (WT) or caspase 1(-/-) mice were injected intraperitoneally
      with phosphate buffered saline or pristane. Six months after injection, mice were
      euthanized, and the development of a lupus phenotype and vascular dysfunction was
      assessed. RESULTS: While WT mice exposed to pristane developed autoantibodies and
      a strong type I interferon response, mice lacking caspase 1 were significantly
      protected against these features as well as against pristane-induced vascular
      dysfunction. Further, the development of immune complex glomerulonephritis, which
      was prominent after pristane exposure in WT mice, was significantly abrogated in
      caspase 1(-/-) mice. CONCLUSION: These results indicate that caspase 1 is an
      essential component in the development of lupus and its associated vascular
      dysfunction and that it may play an important role in the cross-talk between
      environmental exposures and autoimmunity development, thus identifying a novel
      pathway for therapeutic targeting.

PMID- 24449583
TI  - Estrogen receptor alpha regulates tripartite motif-containing protein 21
      expression, contributing to dysregulated cytokine production in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To examine the role of 17beta-estradiol in the regulation of the
      autoantigen tripartite motif-containing protein 21 (TRIM-21) in patients with
      systemic lupus erythematosus (SLE). METHODS: Monocytes isolated from healthy
      control subjects and patients with SLE were stimulated with 17beta-estradiol
      and/or the estrogen receptor alpha (ERalpha) antagonist methyl-piperidino
      pyrazole dihydrochloride. TRIM-21, ERalpha, and CREMalpha expression was
      determined by real-time polymerase chain reaction (PCR) analysis. MatInspector
      software was used to identify putative binding sites within the TRIM-21 promoter.
      ERalpha binding to the TRIM-21 gene promoter region in monocytes was analyzed by
      chromatin immunoprecipitation (ChIP) assay. TRIM-21 and interferon regulatory
      factor 3 protein levels were analyzed by Western blotting. RESULTS: Real-time PCR
      analysis demonstrated a role of estrogen in the regulation of TRIM-21 expression
      in monocytes, which correlated positively with ERalpha gene expression in
      patients with SLE. Investigations into the human TRIM-21 promoter revealed the
      presence of an estrogen response element, with ChIP assays confirming ERalpha
      binding to this site. Studies into estrogen-induced TRIM-21 expression revealed a
      hyperresponsiveness of SLE patients to 17beta-estradiol, which led to the
      enhanced levels of TRIM-21 observed in these individuals. CONCLUSION: Our results
      demonstrate a role of estrogen in the regulation of TRIM-21 expression through an
      ERalpha-dependent mechanism, a pathway that we observed to be overactive in SLE
      patients. Treatment of monocytes with an ERalpha antagonist abrogated estrogen
      induced TRIM-21 expression and, as a consequence, decreased the expression of
      interleukin-23. These findings identify TRIM-21 as a novel ERalpha-regulated gene
      and provide novel insights into the link between estrogen and the molecular
      pathogenesis of SLE.

PMID- 24449584
TI  - Use of diuretics and risk of incident gout: a population-based case-control
      study.
AB  - OBJECTIVE: Use of diuretics has been associated with an increased risk of gout.
      Data on different types of diuretics are scarce. We undertook this study to
      investigate the association between use of loop diuretics, thiazide or thiazide
      like diuretics, and potassium-sparing agents and the risk of developing incident
      gout. METHODS: We conducted a retrospective population-based case-control
      analysis using the General Practice Research Database established in the UK. We
      identified case patients who were diagnosed as having incident gout between 1990
      and 2010. One control patient was matched to each case patient for age, sex,
      general practice, calendar time, and years of active history in the database. We
      used conditional logistic regression to calculate odds ratios (ORs) and 95%
      confidence intervals (95% CIs), and we adjusted for potential confounders.
      RESULTS: We identified 91,530 incident cases of gout and the same number of
      matched controls. Compared to past use of diuretics from each respective drug
      class, adjusted ORs for current use of loop diuretics, thiazide diuretics,
      thiazide-like diuretics, and potassium-sparing diuretics were 2.64 (95% CI 2.47
      2.83), 1.70 (95% CI 1.62-1.79), 2.30 (95% CI 1.95-2.70), and 1.06 (95% CI 0.91
      1.23), respectively. Combined use of loop diuretics and thiazide diuretics was
      associated with the highest relative risk estimates of gout (adjusted OR 4.65
      [95% CI 3.51-6.16]). Current use of calcium channel blockers or losartan slightly
      attenuated the risk of gout in patients who took diuretics. CONCLUSION: Use of
      loop diuretics, thiazide diuretics, and thiazide-like diuretics was associated
      with an increased risk of incident gout, although use of potassium-sparing agents
      was not.

PMID- 24449585
TI  - Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia.
AB  - OBJECTIVE: While patients with fibromyalgia (FM) are known to exhibit
      hyperalgesia, the central mechanisms contributing to this altered pain processing
      are not fully understood. This study was undertaken to investigate potential
      dysregulation of the neural circuitry underlying cognitive and hedonic aspects of
      the subjective experience of pain, such as anticipation of pain and anticipation
      of pain relief. METHODS: Thirty-one FM patients and 14 controls underwent
      functional magnetic resonance imaging, while receiving cuff pressure pain stimuli
      on the leg calibrated to elicit a pain rating of ~50 on a 100-point scale. During
      the scan, subjects also received visual cues informing them of the impending
      onset of pain (pain anticipation) and the impending offset of pain (relief
      anticipation). RESULTS: Patients exhibited less robust activation during both
      anticipation of pain and anticipation of relief within regions of the brain
      commonly thought to be involved in sensory, affective, cognitive, and pain
      modulatory processes. In healthy controls, direct searches and region-of-interest
      analyses of the ventral tegmental area revealed a pattern of activity compatible
      with the encoding of punishment signals: activation during anticipation of pain
      and pain stimulation, but deactivation during anticipation of pain relief. In FM
      patients, however, activity in the ventral tegmental area during periods of pain
      and periods of anticipation (of both pain and relief) was dramatically reduced or
      abolished. CONCLUSION: FM patients exhibit disrupted brain responses to
      reward/punishment. The ventral tegmental area is a source of reward-linked
      dopaminergic/gamma-aminobutyric acid-releasing (GABAergic) neurotransmission in
      the brain, and our observations are compatible with reports of altered
      dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment
      signaling in FM may be related to the augmented central processing of pain and
      reduced efficacy of opioid treatments in these patients.

PMID- 24449586
TI  - Detection of enthesitis in children with enthesitis-related arthritis:
      dolorimetry compared to ultrasonography.
AB  - OBJECTIVE: To evaluate the distribution of enthesitis and the accuracy of
      physical examination with a dolorimeter for the detection of enthesitis in
      children, using ultrasound (US) assessment as the reference standard. METHODS: We
      performed a prospective cross-sectional study of 30 patients with enthesitis
      related arthritis (ERA) and 30 control subjects. The following tendon insertion
      sites were assessed by standardized physical examination with a dolorimeter and
      US: common extensor on the lateral humeral epicondyle, common flexor on the
      medial humeral epicondyle, quadriceps at the superior patella, patellar ligament
      at the inferior patella, Achilles, and plantar fascia at the calcaneus. RESULTS:
      Abnormal findings on US were detected most commonly at the insertion of the
      quadriceps (30% [18 of 60 sites]), common extensor (12% [7 of 60]), and Achilles
      (10% [6 of 60]) tendons. The intrarater reliability of US (kappa statistic) was
      0.78 (95% confidence interval [95% CI] 0.63-0.93), and the interrater reliability
      was 0.81 (95% CI 0.67-0.95). Tenderness as detected by standardized dolorimeter
      examination had poor positive predictive value for US-confirmed enthesitis. In
      comparison to controls, patients with ERA reported more pain and had lower pain
      thresholds at every site, including control sites (P < 0.001 for all
      comparisons). The interrater reliability of dolorimeter examination for detection
      of enthesitis was low (kappa = 0.49 [95% CI 0.33-0.65]). CONCLUSION: Compared to
      US, standardized dolorimeter examination for the detection of enthesitis in
      children has poor accuracy and reliability. The decreased pain threshold of ERA
      patients likely contributed to the limited accuracy of the physical examination
      findings. Further research regarding the utility of US for identifying enthesitis
      at diagnosis of juvenile idiopathic arthritis, accurately predicting disease
      progression, and guiding therapeutic decisions is warranted.

PMID- 24449587
TI  - The potential negative effect of high-dose glucosamine on the chondrocyte:
      comment on the article by Carames et al.

PMID- 24449588
TI  - Protein kinase Cdelta mutations may contribute to lupus through effects on T
      cells: comment on the article by Belot et al.

PMID- 24449589
TI  - Reply: To PMID 23666743.

PMID- 24449590
TI  - Continuous blood glucose monitoring in a patient with type 2 diabetes who
      underwent intraarticular betamethasone injection for knee osteoarthritis.

PMID- 24449591
TI  - Selective extraction of clonazepam from  human plasma and urine samples by 
      molecularly imprinted polymeric beads.
AB  - A molecularly imprinted polymer (MIP) based on free-radical polymerization was
      prepared with 1-(N,N-biscarboxymethyl)amino-3-allylglycerol and N,N
      dimethylacrylamide as functional monomers, N,N-methylene diacrylamide as the
      cross-linker, copper ion-clonazepam as the template and 2,2-azobis(2
      methylbutyronitrile) as the initiator. The imprinted polymer was characterized by
      Fourier transform infrared spectroscopy, elemental analysis, thermo-gravimetric
      analysis, and SEM. The MIP of agglomerated microparticles with multipores was
      used for SPE. The imprinted polymer sorbent was selective for clonazepam. The
      optimum pH and sorption capacity were 5 and 0.18 mg/g at 20C, respectively. The
      profile of the drug uptake by the sorbent reflects good accessibility of the
      active sites in the imprinted polymer sorbent. The MIP-SPE was the most feasible
      technique for the extraction of clonazepam with a high recovery from human plasma
      and urine samples.

PMID- 24449592
TI  - Reorientational dynamics of water confined in zeolites.
AB  - We present a detailed molecular-dynamics study of water reorientation and
      hydrogen-bond dynamics in a strong confinement situation, within the narrow pores
      of an all-silica Linde type A (LTA) zeolite. Two water loadings of the zeolite
      are compared with the bulk case. Water dynamics are retarded in this extreme
      hydrophobic confinement and the slowdown is more pronounced at higher water
      loading. We show that water reorientation proceeds mainly by large-amplitude
      angular jumps, whose mechanism is similar to that determined in the bulk. The
      slowdown upon hydrophobic confinement arises predominantly from an excluded
      volume effect on the large fraction of water molecules lying at the interface
      with the zeolite matrix, with an additional minor contribution coming from a
      structuring effect induced by the confinement. 

PMID- 24449593
TI  - Reduced graphene oxide hydrogels and xerogels provide efficient platforms for
      immobilization and laccase production by Trametes pubescens.
AB  - Fungal immobilization is an interesting topic in enzyme production and bioprocess
      development. The properties of graphene (i.e. large surface area,
      hydrophobicity), together with the possibility of producing it at low cost and
      with tailor-made properties, make this popular material worthy of investigation
      as a support for fungal immobilization. In the present paper, 3D-organized
      structures of reduced graphene oxide (rGO) in hydrogels and their dried
      derivatives (xerogels) were synthesized, characterized and investigated as
      potential supports for the immobilization of the white-rot fungus Trametes
      pubescens. It was found that the morphology of the hydrogels and xerogels was not
      influenced by the synthesis conditions; however the 3D structure was preserved
      after drying and formation of xerogels. Both, hydrogels and xerogels have been
      shown to be suitable supports for the immobilization of T. pubescens.
      Additionally, xerogels promoted increased laccase activities and maximum activity
      values of about 20 +/- 1 U/mL were attained. These activities were much higher
      than those obtained with other well-known inert supports. Nevertheless, no
      relationship between support morphology and productivity was found. The
      encouraging results obtained have paved the way for the development of novel
      graphene-based supports for microorganism immobilization. 

PMID- 24449594
TI  - Preoperative PET and the reduction of unnecessary surgery among newly diagnosed
      lung cancer patients in a community setting.
AB  - The goals of this study were to examine the real-world effectiveness of PET in
      avoiding unnecessary surgery for newly diagnosed patients with non-small cell
      lung cancer. METHODS: A cohort of 2,977 veterans with non-small cell lung cancer
      between 1997 and 2009 were assessed for use of PET during staging and treatment
      planning. The subgroup of 976 patients who underwent resection was assessed for
      several outcomes, including pathologic evidence of mediastinal lymph node
      involvement, distant metastasis, and 12-mo mortality. We anticipated that PET may
      have been performed selectively on the basis of unobserved characteristics (e.g.,
      providers ordered PET when they suspected disseminated disease). Therefore, we
      conducted an instrumental variable analysis, in addition to conventional
      multivariate logistic regression, to reduce the influence of this potential bias.
      This type of analysis attempts to identify an additional variable that is related
      to receipt of treatment but not causally associated with the outcome of interest,
      similar to randomized assignment. The instrument here was calendar time. This
      analysis can be informative when patients do not receive the treatment that the
      instrument suggests they "should" have received. RESULTS: Overall, 30.3% of
      patients who went to surgery were found to have evidence of metastasis uncovered
      during the procedure or within 12 mo, indicating that nearly one third of
      patients underwent surgery unnecessarily. The use of preoperative PET increased
      substantially over the study period, from 9% to 91%. In conventional multivariate
      analyses, PET use was not associated with a decrease in unnecessary surgery (odds
      ratio, 0.87; 95% confidence interval, 0.66-1.16; P = 0.351). However, a reduction
      in unnecessary surgery (odds ratio, 0.53; 95% confidence interval, 0.34-0.82; P =
      0.004) was identified in the instrumental variable analyses, which attempted to
      account for potentially unobserved confounding. CONCLUSION: PET has now become
      routine in preoperative staging and treatment planning in the community and
      appears to be beneficial in avoiding unnecessary surgery. Evaluating the
      effectiveness of PET appears to be influenced by potentially unmeasured adverse
      selection of patients, especially when PET first began to be disseminated in the
      community.

PMID- 24449595
TI  - Reply: Human Cerenkov imaging using 18F-FDG.

PMID- 24449596
TI  - Human Cerenkov imaging using 18F-FDG.

PMID- 24449598
TI  - Marketing of e-cigarettes should follow the rules laid down for tobacco
      advertising.

PMID- 24449597
TI  - Administration of a loading dose has no additive effect on platelet aggregation
      during the switch from ongoing clopidogrel treatment to ticagrelor in patients
      with acute coronary syndrome.
AB  - BACKGROUND: Ticagrelor outperforms clopidogrel in preventing cardiovascular
      events in acute coronary syndrome. Despite the inclusion of a loading dose in the
      Platelet Inhibition and Patient Outcomes (PLATO) trial for all patients
      randomized to ticagrelor, it may not be necessary in patients receiving ongoing
      clopidogrel therapy. The aim of the present study was to assess whether a
      ticagrelor loading dose is associated with a further platelet inhibition during
      the switch from clopidogrel to ticagrelor in patients with acute coronary
      syndrome receiving ongoing antiplatelet treatment. METHODS AND RESULTS: Fifty
      patients with acute coronary syndrome receiving aspirin and clopidogrel treatment
      were randomly assigned to a starting dose of ticagrelor (group 1, 90 mg; group 2,
      180 mg). Platelet aggregation was measured using multiple electrode aggregometry
      and standard light transmission aggregometry just before the switch and at 2, 6,
      24, and 72 hours. No relevant difference in platelet aggregation was observed
      between the 2 study arms at baseline (P=0.256). Residual platelet aggregation was
      significantly reduced in both arms 2 hours after the first administration of
      ticagrelor (P<0.001 for both), with no difference in aggregation between groups
      (multiple electrode aggregometry, 17.6+/-7.2 versus 18.1+/-6 U; P=0.281). Similar
      results were observed with LTA. CONCLUSIONS: Switching from clopidogrel to
      ticagrelor without a reloading dose is feasible, and it does not hinder platelet
      aggregation inhibition in patients with acute coronary syndrome. Further
      prospective studies are needed to assess the clinical relevance of our findings.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01795820.

PMID- 24449599
TI  - Dupuytren's contracture and occupational exposure to hand-transmitted vibration.
AB  - AIMS: The relation between Dupuytren's contracture and occupational exposure to
      hand-transmitted vibration (HTV) has frequently been debated. We explored
      associations in a representative national sample of workers with well
      characterised exposure to HTV. METHODS: We mailed a questionnaire to 21 201
      subjects aged 16-64 years, selected at random from the age-sex registers of 34
      general practices in Great Britain and to 993 subjects chosen randomly from
      military pay records, asking about occupational exposure to 39 sources of HTV and
      about fixed flexion contracture of the little or ring finger. Analysis was
      restricted to men at work in the previous week. Estimates were made of average
      daily vibration dose (A(8) root mean squared velocity (rms)) over that week.
      Associations with Dupuytren's contracture were estimated by Poisson regression,
      for lifetime exposure to HTV and for exposures in the past week >A(8) of 2.8 ms(
      2) rms. Estimates of relative risk (prevalence ratio (PR)) were adjusted for age,
      smoking status, social class and certain manual activities at work. RESULTS: In
      all 4969 eligible male respondents supplied full information on the study
      variables. These included 72 men with Dupuytren's contracture, 2287 with
      occupational exposure to HTV and 409 with A(8)>2.8 ms(-2) in the past week. PRs
      for occupational exposure to HTV were elevated 1.5-fold. For men with an A(8)>2.8
      ms(-2) in the past week, the adjusted PR was 2.85 (95% CI 1.37 to 5.97).
      CONCLUSIONS: Our findings suggest that risk of Dupuytren's contracture is more
      than doubled in men with high levels of weekly exposure to HTV.

PMID- 24449600
TI  - Morphological analysis of lymph nodes in Odontocetes from north and northeast
      coast of Brazil.
AB  - The morphology and location of lymph nodes from seven species of Odontocetes, of
      both sexes and different age groups, were described. All animals were derived
      from stranding events along the North and Northeastern coasts of Brazil. After
      the identification of lymph nodes in situ, tissue samples were analyzed for light
      and electron microscopy. Vascular volume density (VVD) and vascular length
      density (VLD) were evaluated in the mesenteric lymph nodes. Lymph nodes occurred
      as solitary nodules or in groups, varying in shape and size. In addition to using
      the nomenclature recommended by Nomina Anatomica Veterinaria, new nomenclatures
      were suggested based on the lymph nodes topography. Lymph nodes were covered by a
      highly vascularized and innervated capsule of dense connective tissue, below
      which muscle fibers were observed, inconsistently, in all studied species. There
      was no difference in VLD among different age groups. However, VVD was higher in
      adults. Lymph nodes parenchyma was divided into an outer cortex, containing lymph
      nodules and germinal centers; a paracortical region, transition zone with dense
      lymphoid tissue; and an inner medulla, composed of small irregular cords of
      lymphatic tissue, blood vessels, and diffuse lymphoid tissue. Abundant collagen
      fibers were observed around arteries and arterioles. Germinal centers were more
      evident and developed in calves and young animals, being more discrete and sparse
      in adults. The morphology of lymph nodes in Odontocetes was typical of that
      observed in other terrestrial mammals. However, new groups of lymph nodes were
      described for seven species occurring in the Brazilian coast.

PMID- 24449601
TI  - Single-step affinity purification of enzyme biotherapeutics: a platform
      methodology for accelerated process development.
AB  - Downstream sample purification for quality attribute analysis is a significant
      bottleneck in process development for non-antibody biologics. Multi-step
      chromatography process train purifications are typically required prior to many
      critical analytical tests. This prerequisite leads to limited throughput, long
      lead times to obtain purified product, and significant resource requirements. In
      this work, immunoaffinity purification technology has been leveraged to achieve
      single-step affinity purification of two different enzyme biotherapeutics
      (Fabrazyme(r) [agalsidase beta] and Enzyme 2) with polyclonal and monoclonal
      antibodies, respectively, as ligands. Target molecules were rapidly isolated from
      cell culture harvest in sufficient purity to enable analysis of critical quality
      attributes (CQAs). Most importantly, this is the first study that demonstrates
      the application of predictive analytics techniques to predict critical quality
      attributes of a commercial biologic. The data obtained using the affinity columns
      were used to generate appropriate models to predict quality attributes that would
      be obtained after traditional multi-step purification trains. These models
      empower process development decision-making with drug substance-equivalent
      product quality information without generation of actual drug substance.
      Optimization was performed to ensure maximum target recovery and minimal target
      protein degradation. The methodologies developed for Fabrazyme were successfully
      reapplied for Enzyme 2, indicating platform opportunities. The impact of the
      technology is significant, including reductions in time and personnel
      requirements, rapid product purification, and substantially increased throughput.
      Applications are discussed, including upstream and downstream process development
      support to achieve the principles of Quality by Design (QbD) as well as
      integration with bioprocesses as a process analytical technology (PAT).

PMID- 24449602
TI  - A novel diazoresin/poly(N-vinyl aminobutyric acid) covalent capillary coating for
      the analysis of proteins by capillary electrophoresis.
AB  - A novel method for the preparation of covalently linked capillary coatings of
      poly(N-vinyl aminobutyric acid) (PVAA) obtained from hydrolyzed
      polyvinylpyrrolidone was demonstrated using photosensitive diazoresin (DR) as a
      coupling agent. A layer-by-layer self-assembled film of DR and PVAA based on
      ionic bonding was first fabricated on the inner wall of capillary, then ionic
      bonding was converted into covalent bonding after treatment with UV light through
      a unique photochemical reaction of DR. The covalently bonded coatings suppressed
      protein adsorption on the inner surface of the capillary, and thus a baseline
      separation of lysozyme, cytochrome c, BSA, amyloglucosidase, and myoglobin was
      achieved using CE. Compared with bare capillary or noncovalently bonded DR/PVAA
      coatings, the covalently linked DR/PVAA capillary coatings not only improved the
      CE separation performance for proteins, but also exhibited good stability and
      repeatability. Due to the replacement of the 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 covalently coated capillaries for CE. 

PMID- 24449603
TI  - Vocational support approaches in autism spectrum disorder: a synthesis review of
      the literature.
AB  - This synthesis-based analysis identifies and reviews studies evaluating
      vocational resources for adults with autism spectrum disorder. It is based on a
      larger systematic review of intervention studies in autism spectrum disorder,
      from which a critical interpretive synthesis was conducted on studies related to
      vocation and autism spectrum disorder. In total, 10 studies were found that
      examine employment support for youth and adults with autism spectrum disorder.
      Two domains of vocational intervention in the literature were found: supported
      employment including community placement and job coaching and media and
      technology-based augmentative tools. The literature is limited in volume and
      quality of methodology, yet emerging constructs are promising in introducing the
      utility of vocational resources, in particular, supported employment in community
      settings. These vocational approaches are examined, along with representative
      studies. Recommendations for advancing practice, community capacity, and research
      are offered. 

PMID- 24449604
TI  - Reading and math achievement profiles and longitudinal growth trajectories of
      children with an autism spectrum disorder.
AB  - This study examined the reading and math achievement profiles and longitudinal
      growth trajectories of a nationally representative sample of children ages 6
      through 9 with an autism spectrum disorder. Four distinct achievement profiles
      were identified: higher-achieving (39%), hyperlexia (9%), hypercalculia (20%) and
      lower-achieving (32%). Children with hypercalculia and lower-achieving profiles
      were more likely to be from low socioeconomic families and had lower functional
      cognitive skills than the higher-achieving profile. All four profiles lost ground
      in passage comprehension over time. Slower improvement occurred for the higher
      achieving group on letter-word identification, the hyperlexia group on
      conversation abilities and the hypercalculia group on calculation and functional
      cognitive skills relative to the lower-achieving group. 

PMID- 24449605
TI  - Commentary on employment supports research.

PMID- 24449606
TI  - ZEBRA cell-penetrating peptide as an efficient delivery system in Candida
      albicans.
AB  - There is increasing interest in drug delivery systems, such as nanoparticles,
      liposomes, and cell-penetrating peptides, for the development of new
      antimicrobial treatments. In this study, we investigated the transduction
      capacity of a carrier peptide derived from the Epstein-Barr virus ZEBRA protein
      in the pathogenic fungus Candida albicans. ZEBRA-minimal domain (MD) was able to
      cross the cell wall and cell membrane, delivering eGFP to the cytoplasm. Uptake
      into up to 70% of the cells was observed within two hours, without toxicity. This
      new delivery system could be used in C. albicans as a carrier for different
      biological molecules including peptides, proteins, and nucleic acids. Thereby, in
      antifungal therapy, MD may carry promising bioactive fungal inhibitors that
      otherwise penetrate poorly into the cells. Furthermore, MD will be of interest
      for deciphering molecular pathways involving cell-cycle control in yeast or
      signaling pathways. Short interfering peptides could be internalized using MD,
      providing new tools for the inhibition of metabolic or signaling cascades
      essential for the growth and virulence of C. albicans, such as yeast-to-hyphae
      transition, cell wall remodeling, stress signaling and antifungal resistance.
      These findings create new possibilities for the internalization of cargo
      molecules, with applications for both treatment and functional analyses. 

PMID- 24449608
TI  - NICE guidance does not currently recommend e-cigarettes.

PMID- 24449607
TI  - Recent advances in computational methodology for simulation of mechanical
      circulatory assist devices.
AB  - Ventricular assist devices (VADs) provide mechanical circulatory support to
      offload the work of one or both ventricles during heart failure. They are used in
      the clinical setting as destination therapy, as bridge to transplant, or more
      recently as bridge to recovery to allow for myocardial remodeling. Recent
      developments in computational simulation allow for detailed assessment of VAD
      hemodynamics for device design and optimization for both children and adults.
      Here, we provide a focused review of the recent literature on finite element
      methods and optimization for VAD simulations. As VAD designs typically fall into
      two categories, pulsatile and continuous flow devices, we separately address
      computational challenges of both types of designs, and the interaction with the
      circulatory system with three representative case studies. In particular, we
      focus on recent advancements in finite element methodology that have increased
      the fidelity of VAD simulations. We outline key challenges, which extend to the
      incorporation of biological response such as thrombosis and hemolysis, as well as
      shape optimization methods and challenges in computational methodology.

PMID- 24449609
TI  - Protein-coated polymer as a matrix for enzyme immobilization: immobilization of
      trypsin on bovine serum albumin-coated allyl glycidyl ether-ethylene glycol
      dimethacrylate copolymer.
AB  - Allyl glycidyl ether (AGE)-ethylene glycol dimethacrylate (EGDM) copolymer with
      25% crosslink density (AGE-25) shows excellent bovine serum albumin (BSA)
      adsorption (up to 16% (w/w)) at pH 8.0 and the adsorbed BSA is strongly bound.
      This protein-coated polymer provides a novel matrix with naturally existing
      functional groups such as thiol, amino, and carboxylic acid that are available
      for covalent immobilization of functional enzymes. Employing appropriate
      strategies, trypsin as a model protein was covalently bound to BSA-coated matrix
      both independently, and in a stepwise manner on the same matrix, with less than
      5% loss of enzyme activity during immobilization. Glutaraldehyde crosslinking
      after immobilization provide stable enzyme preparation with activity of 510
      units/g recycled up to six times without loss of enzyme activity. AFM studies
      reveal that the polymer surface has protein peaks and valleys rather than a
      uniform monolayer distribution of the protein and the immobilized enzyme
      preparation can best be described as polymer supported cross-linked enzyme
      aggregates (CLEAs).

PMID- 24449610
TI  - The role of ligands on protein retention in adsorption chromatography: a surface
      energetics approach.
AB  - Protein adsorption onto hydrophobic chromatographic supports has been
      investigated using a colloid theory surface energetics approach. The surface
      properties of commercially available chromatographic beads, Toyopearl Phenyl 650
      C, and Toyopearl Butyl 650-C, have been experimentally determined by contact
      angle and zeta potential measurements. The adsorption characteristics of these
      beads, which bear the same backbone matrix but harbor different ligands, have
      been studied toward selected model proteins, in the hydrated as well as
      dehydrated state. There were two prominent groups of proteins observed with
      respect to the chromatographic supports presented in this work: loosely retained
      proteins, which were expected to have lower average interaction energies, and the
      strongly retained proteins, which were expected to have higher average
      interaction energies. Results were also compared and contrasted with calculations
      derived from adsorbent surface energies determined by inverse liquid
      chromatography. These results showed a good qualitative agreement, and the
      interaction energy minima obtained from these extended Derjaguin, Landau, Verwey
      and Overbeek calculations were shown to correlate well with the experimentally
      determined adsorption behavior of each protein. 

PMID- 24449611
TI  - Allergic reactions to insect secretions.
AB  - Some products derived from insects can induce allergic reactions. The main
      characteristics of some products from honeybees, cochineal and silkworms are
      summarised here. We review allergic reactions from honey-derived products
      (propolis, wax, royal jelly), from cochineal products (shellac and carmine) and
      from silk : clinical features, allergological investigations and allergens if
      they are known. 

PMID- 24449612
TI  - Mind the methyl: methyllysine binding proteins in epigenetic regulation.
AB  - Epigenetics is defined as the phenomenon of heritable phenotypic traits that are
      not governed by alteration of the genetic code. Major epigenetic control
      mechanisms include DNA methylation and post-translational modifications of
      histones, such as reversible histone acetylation and methylation of lysine
      residues. Methyllysine binding proteins recognize various levels of lysine
      methylation and mediate the signaling events that are induced by histone
      methylation. Therefore, they are also referred to as readers of the epigenetic
      code. In this article we review the current literature on the structure and
      biology of methyllysine binding proteins, especially with regard to their
      potential as drug targets. We also present the available inhibitors that block
      the interaction of methylated histones with their binding proteins. 

PMID- 24449613
TI  - An alternate diafiltration strategy to mitigate protein precipitation for low
      solubility proteins.
AB  - Application of the minimum diafiltration (DF) time solution for a monoclonal
      antibody resulted in a 20-h process time rather than the expected 12 h. Further
      investigation indicated high turbidity associated with a product solubility issue
      that caused a flux decline. As a result, the gel flux model and the associated
      minimum DF time were not predictive. Multiwell plate solubility screening
      confirmed that the protein passed through a region of low solubility during the
      ultrafiltration step. Multiple approaches to address this issue were considered
      and a new strategy involving variable volume diafiltration (VVDF) was developed.
      Process modeling and simulation were used to predict performance and to select a
      value of the DF ratio control parameter (buffer flow/permeate flow = 0.65).
      Feasibility testing at the bench and pilot scales confirmed that the new strategy
      reduced solubility issues, fit within existing manufacturing tank volume and
      system area constraints, matched model predictions, and did not present
      significant implementation issues. Recommendations are made regarding the general
      value of this strategy, when it should be used, and how to implement it.

PMID- 24449614
TI  - Is it OK to fire my oncologist?

PMID- 24449615
TI  - Reflections.

PMID- 24449616
TI  - Severe bereavement stress during the prenatal and childhood periods and risk of
      psychosis in later life: population based cohort study.
AB  - OBJECTIVE: To examine the risk of psychosis associated with severe bereavement
      stress during the antenatal and postnatal period, between conception to
      adolescence, and with different causes of death. DESIGN: Population based cohort
      study. SETTING: Swedish national registers including births between 1973 and 1985
      and followed-up to 2006. PARTICIPANTS: In a cohort of 1,045,336 Swedish births
      (1973-85), offspring born to mothers exposed to severe maternal bereavement
      stress six months before conception or during pregnancy, or exposed to loss of a
      close family member subsequently from birth to 13 years of age were followed
      until 2006. Admissions were identified by linkage to national patient registers.
      MAIN OUTCOME MEASURES: Crude and adjusted odds ratios for all psychosis, non
      affective psychosis, and affective psychosis. RESULTS: Maternal bereavement
      stress occurring preconception or during the prenatal period was not associated
      with a significant excess risk of psychosis in offspring (adjusted odds ratio,
      preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95,
      0.58 to 1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to
      1.66). Risks increased modestly after exposure to the loss of a close family
      member from birth to adolescence for all psychoses (adjusted odds ratio 1.17,
      1.04 to 1.32). The pattern of risk was generally similar for non-affective and
      affective psychosis. Thus estimates were higher after death in the nuclear
      compared with extended family but remained non-significant for prenatal exposure;
      the earlier the exposure to death in the nuclear family occurred in childhood
      (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9
      years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide.
      Following suicide, risks were especially higher for affective psychosis (birth to
      2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68,
      1.84 to 3.92). Adjustment for key confounders attenuated but did not explain
      associations with risk. CONCLUSIONS: Postnatal but not prenatal bereavement
      stress in mothers is associated with an increased risk of psychosis in offspring.
      Risks are especially high for affective psychosis after suicide in the nuclear
      family, an effect that is not explained by family psychiatric history. Future
      studies are needed to understand possible sources of risk and resilience so that
      structures can be put in place to support vulnerable children and their families.

PMID- 24449618
TI  - Synthesis, purification, and chemical characterization of 20-dihydro-6
      methylprednisone, an isomeric metabolite of methylprednisolone in the horse, for
      use as an analytical standard.

PMID- 24449619
TI  - High-throughput ion exchange purification of positively charged recombinant
      protein in the presence of negatively charged dextran sulfate.
AB  - Product quality analyses are critical for developing cell line and bioprocess
      producing therapeutic proteins with desired critical product quality attributes.
      To facilitate these analyses, a high-throughput small-scale protein purification
      (SSP) is required to quickly purify many samples in parallel. Here we develop an
      SSP using ion exchange resins to purify a positively charged recombinant growth
      factor P1 in the presence of negatively charged dextran sulfate supplemented to
      improve the cell culture performance. The major challenge in this work is that
      the strong ionic interaction between P1 and dextran sulfate disrupts interaction
      between P1 and chromatography resins. To solve this problem, we develop a two
      step SSP using Q Sepharose Fast Flow (QFF) and SP Sepharose XL (SPXL) resins to
      purify P1. The overall yield of this two-step SSP is 78%. Moreover, the SSP does
      not affect the critical product quality attributes. The SSP was critical for
      developing the cell line and process producing P1.

PMID- 24449620
TI  - Novel heterobimetallic radiotheranostic: preparation, activity, and
      biodistribution.
AB  - A novel Ru(II) (arene) theranostic complex is presented. It is based on a
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a
      triarylphosphine and can be tracked in vivo by using the gamma emission of (153)
      Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with
      ruthenium at the phosphorus atom despite the presence of other functionalities
      that are prone to metal coordination. Subsequent labeling with radionuclides such
      as (153) Sm can then be performed easily. The resulting heterobimetallic complex
      exhibits favorable solubility and stability properties in biologically relevant
      media. It also shows in vitro cytotoxicity in line with that expected for this
      type of metallodrug, and is nontoxic to the organism as a whole. As a proof of
      concept, initial studies in healthy mice were performed to obtain information
      about the uptake, biodistribution, and excretion of the radiolabeled complex. 

PMID- 24449617
TI  - Lysine deacetylase (KDAC) regulatory pathways: an alternative approach to
      selective modulation.
AB  - Protein lysine deacetylases (KDACs), including the classic Zn(2+) -dependent
      histone deacetylases (HDACs) and the nicotinamide adenine dinucleotide (NAD(+) )
      requiring sirtuins, are enzymes that play critical roles in numerous biological
      processes, particularly the epigenetic regulation of global gene expression
      programs in response to internal and external cues. Dysregulation of KDACs is
      characteristic of several human diseases, including chronic metabolic,
      neurodegenerative, and cardiovascular diseases and many cancers. This has led to
      the development of KDAC modulators, two of which (HDAC inhibitors vorinostat and
      romidepsin) have been approved for the treatment of cutaneous T cell lymphoma. By
      their nature, existing KDAC modulators are relatively nonspecific, leading to pan
      KDAC changes and undesired side effects. Given that KDACs are regulated at many
      levels, including transcriptional, post-translational, subcellular localization,
      and through their complexation with other proteins, it should be possible to
      affect specific KDAC activity through manipulation of endogenous signaling
      pathways. In this Minireview, we discuss our present knowledge of the cellular
      controls of KDAC activity and examples of their pharmacologic regulation. 

PMID- 24449621
TI  - Elevated serum gamma-glutamyltransferase levels in patients with dilated
      ascending aorta.
AB  - OBJECTIVE: This study aimed to evaluate the serum gamma-glutamyltransferase (GGT)
      levels as an indirect marker of elevated oxidative stress in patients with
      dilated ascending aorta. METHODS: The study was designed as an observational
      cross-sectional controlled study. One hundred consecutive patients with dilated
      ascending aorta and 50 consecutive controls with normal ascending aorta diameter
      were selected for the study by comprehensive transthoracic echocardiography
      (TTE). The aortic dilatation group was divided into two subgroups, according to
      the literature as the ectasia group (3.8-4.3 cm, 53 patients, 24 male and 29
      female, mean age: 62.9+/-10.9 years) and the aneurysm group (>=4.4 cm, 47
      patients, 18 male and 29 female, mean age: 65.5+/-11.1 years). The control group
      consisted of patients demonstrating no ascending aorta dilatation (<=3.7 cm, 50
      patients, 24 male and 26 female, mean age: 62.7+/-9.2 years). ANOVA, Mann-Whitney
      U test, Pearson's correlation analysis, multivariate logistic regression
      analysis, and receiver-operator curve analysis were used for statistical
      analysis. RESULTS: Regarding the comparison of laboratory parameters between the
      patient and control groups, serum gamma-glutamyltransferase (GGT) levels were
      found to be statistically significantly higher in both of the aortic dilatation
      subgroups than in the control group (p<0.001). In the correlation analysis
      between the ascending aorta diameter and GGT, a statistically significant
      positive correlation was found (r=0.282, p<0.001). The multivariate regression
      analysis revealed a significant relationship between GGT and the proximal
      ascending aorta diameter (beta=0.131, odds ratio: 1.140, 95% CI: 1.060-1.225,
      p<0.001). CONCLUSION: GGT as a marker of oxidative stress may play a role in the
      pathogenesis of aneurysm of the ascending aorta.

PMID- 24449622
TI  - Is there a relationship between serum paraoxonase level and epicardial fat tissue
      thickness?
AB  - OBJECTIVE: This study aimed to show the relationship between serum paraoxonase 1
      level and the epicardial fat tissue thickness. METHODS: Two hundred and seven
      patients without any atherosclerotic disease history were included in this cross
      sectional observational study. Correlation analysis was performed to determine
      the correlation between epicardial fat tissue thickness, which was measured by
      echocardiography and serum paraoxonase 1 level. Also correlation analysis was
      performed to show correlation between patients' clinical and laboratory findings
      and the level of serum paraoxonase 1 (PON 1) and the epicardial fat tissue
      thickness. Pearson and Spearman test were used for correlation analysis. RESULTS:
      No linear correlation between epicardial fat tissue thickness and serum PON 1
      found (correlation coefficient: -0.127, p=0.069). When epicardial fat tissue
      thickness were grouped as 7 mm and over, and below, and 5 mm and over, and below,
      serum PON 1 level were significantly lower in >=7 mm group (PON1 : 168.9 U/L)
      than <7 mm group (PON 1: 253.9 U/L) (p<0.001). Also hypertension prevalence was
      increased in >=7 mm group (p=0.001). Serum triglyceride was found to be higher in
      >=7 mm group (p=0.014), body mass index was found higher in >=5 mm group
      (p=0.006). CONCLUSION: Serum PON 1 level is not correlated with the epicardial
      fat tissue thickness. But PON 1 level is lower in patients with epicardial fat
      tissue thickness 7 mm and over. Therefore, increased atherosclerosis progression
      can be found among patients with 7 mm and higher epicardial fat tissue thickness.

PMID- 24449623
TI  - Evaluation of the valvular and biventricular functions in Parkinson patients
      using ergotamine-derived dopamine agonist: an observational study.
AB  - OBJECTIVE: In this study, we aimed to evaluate the impact of cabergoline use in
      patients with Parkinson's disease on valvular and biventricular functions.
      METHODS: In this observational cohort study, patients with Parkinson disease were
      divided into 2 groups as 34 patients (41.2% female, age; 57.4+/-15.3 years) using
      cabergoline (Group 1) and 42 patients (61.9% female, age; 53.7+/-7.1 years) not
      using cabergoline (Group 2). In addition to conventional echocardiography and
      diastolic functions, tissue Doppler imaging was used to evaluate both global and
      regional systolic - diastolic functions. Correlations were assessed using Pearson
      correlation coefficient for normally distributed variables. RESULTS: In group 1
      patients cabergoline was used for 7.7+/-5.1 years and mean and cumulative
      cabergoline dose were 3.3+/-1.1 mg and 9.8+/-7.0 g respectively. Left ventricular
      systolic functions and tissue Doppler measurements of septal and lateral mitral
      annulus and right ventricular systolic and diastolic velocities were similar
      between groups. Mitral valve tenting area was significantly higher in patients
      using cabergoline (p=0.007). The association between cumulative cabergoline dose
      and diastolic functions was also evaluated which revealed that among diastolic
      function parameters, Epeak (r=0.253, p=0.042), E/A (r=0.256, p=0.026) and DT (r=
      0.382, p=0.001) were correlated with cumulative cabergoline dose. There was a
      positive correlation between cumulative cabergoline dose and duration of
      cabergoline therapy with composite regurgitation score (r=0.435, p<0.001;
      r=0.485, p<0.001, respectively). CONCLUSION: Our findings indicated that despite
      the well known effects of cabergoline on valvular functions, we did not observe
      any alteration in systolic functions, but diastolic functions which was
      associated with cumulative cabergoline dose in patients with Parkinson's disease.

PMID- 24449624
TI  - Relation of presence and severity of metabolic syndrome with left atrial
      mechanics in patients without overt diabetes: a deformation imaging study.
AB  - OBJECTIVE: We aimed to investigate left atrium (LA) function by speckle tracking
      echocardiography in patients with metabolic syndrome (MetSyn) and to show a
      possible relationship between the severity of MetSyn and LA function and to
      determine the predictors of low strain in MetSyn patients. METHODS: Our study
      design was observational and cross-sectional design consisted of 80 MetSyn
      patients without overt diabetes and 50 controls. The patients were classified
      into three groups based on the number of MetSyn criteria. The peak LA strain at
      the end of the ventricular systole (LAs-strain) as well as the LA strain with LA
      contraction (LAa-strain) was obtained. Correlation analysis performed to assess
      the association of LA strain parameters with the severity of MetSyn and logistic
      regression analysis performed to assess the relationship of low LA strain with
      MetSyn. RESULTS: Both LAs (37.5+/-8.7 vs. 26.0+/-10.2, p<0.001) and LAa (19.9+/
      6.3 vs. 13.0+/-6.4, p<0.001) strain measurements were found to be significantly
      decreased in patients with MetSyn when compared to the control group. Moreover,
      both LAs and LAa were found to be significantly decreased with the increasing
      severity of the MetSyn. A multiple logistic regression analysis demonstrated that
      the presence of MetSyn [OR:0.26 (95% CI 0.06-0.89), p=0.032] and left ventricular
      ejection fraction [OR:1.14 (95% CI 1.03-1.27), p=0.021] were independent
      predictors of LAs strain. CONCLUSION: MetSyn is associated with reduced LAs
      strain and LAa strain representing LA reservoir and pump function, respectively.
      Furthermore, LA mechanical function decreases even more with the increasing
      severity of the MetSyn.

PMID- 24449625
TI  - Diagnostic accuracy of mean platelet volume in prediction of clopidogrel
      resistance in patients with acute coronary syndrome.
AB  - OBJECTIVE: Clopidogrel therapy is the standard of care in patients with acute
      coronary syndrome (ACS) and stent implantation. However, concern arises because
      25% of subjects are nonresponders to clopidogrel. As this nonresponsiveness is
      associated with increased adverse outcome, detection of these subjects in daily
      practice is important in order to withhold a more aggressive therapy and closer
      follow up. In this study we aimed to evaluate the relation between mean platelet
      volume (MPV) which is an indicator of platelet activation and clopidogrel
      nonresponsiveness. METHODS: The study was planned as a prospective cohort study.
      A total of 185 patients who had been on clopidogrel therapy for any acute
      coronary syndrome were enrolled in this study. Clopidogrel responsiveness was
      analyzed by Multiplate MP-0120 device by using the method of whole blood
      aggregometry. Blood samples were drawn 3.5 days after clopidogrel loading dose.
      The amount of ADP induced platelet aggregation was assessed as area under curve
      (AUC), and a cut-off value of 500, above which the patient is considered as
      clopidogrel nonresponder, was used. MPV was analyzed from the blood which were
      sampled at the admission of the patient by using automatic hemocounter.
      Independent sample t-test, ROC analyses and logistic regression analsis were used
      in statistical analysis. RESULTS: Among the 185 patients analyzed 41 were found
      to be clopidogrel nonresponder (22.1%). Mean MPV was found to be significantly
      higher in nonresponders compared to responders (8.7+/-0.82 fL vs. 8.1+/-0.83 fL,
      p<0.001). A cut-off value of 8.3 fL for MPV was detected in prediction of
      clopidogrel nonresponsiveness with a sensitivity of 76.6% and specificity of
      68.3% (OR: 6.4; 95% CI 2.9-14.1, AUC: 0.70, p<0.001). CONCLUSION: This study
      showed that MPV can be used as a predictor of clopidogrel resistance in patients
      with ACS.

PMID- 24449626
TI  - Comparision of pain levels of transradial versus transfemoral coronary
      catheterization: a prospective and randomized study.
AB  - OBJECTIVE: The aim of the present study was to assess access site pain levels of
      patients undergoing coronary catheterization via transradial route. METHODS: We
      performed a prospective and randomized study in which 408 patients underwent
      coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) via
      transradial approach (TRA) and 428 patients underwent CAG and/or PCI via
      transfemoral approach (TFA). Pain levels of patients were assessed with Visual
      Analog Scale (VAS) after catheterization and at 30 days. Student-t, Mann-Whitney
      U and chi-square tests were used for statistical analysis. RESULTS: Patients in
      the TRA group showed higher VAS scores than those in TFA group after
      catheterization [CAG alone, 3 (2-5) vs. 1 (1-3), p<0.0001; PCI, 4 (2-6) vs. 2 (1
      3), p<0.0001, respectively]. One month later, patients in TRA group also showed
      higher VAS scores than those in TFA group [CAG alone, 1 (0-1) vs. 0 (0-1),
      p<0.0001; PCI, 1 (0-2) vs. 0 (0-1), p<0.0001, respectively]. By the ROC analysis
      in TRA group, a level of BMI <24.3 kg/m2 predicted unacceptable pain with a 87.3%
      sensitivity and 91.6% specificity [area under curve (AUC): 0.875, 95% CI: 0.839
      0.906, p<0.0001], while a wrist circumference <16.7 cm predicted unacceptable
      pain with 84.6% sensitivity and 89.8% specificity (AUC: 0.900, 95% CI: 0.867
      0.928, p<0.0001). CONCLUSION: The current study suggests that a radial approach
      for CAG and PCI in patients with a low BMI and small wrist circumference may
      cause more access site pain as compared with a femoral approach.

PMID- 24449627
TI  - Transradial approach: Do we have gain without excessive pain?

PMID- 24449628
TI  - Time for pain: today or tomorrow?

PMID- 24449629
TI  - Clinical features of aviators with coronary artery disease diagnosed by
      multislice CT angiography.
AB  - OBJECTIVE: Coronary artery disease (CAD) is one of the most incapacitating causes
      at military or civilian aviation. Aircrew population is crowding in number in our
      country. We aimed to identify the clinical features that could predict CAD in
      aircrew. METHODS: We retrospectively analyzed medical recordings of 26 aircrew
      (age 43.57+/-5.2) whose CAD was diagnosed via multislice computerized tomography
      angiography (MSCT). Clinical features, coronary risk factors and ST segment and T
      wave changes on resting ECG and treadmill test (TT), and laboratory findings of
      aircrew were recorded. RESULTS: ST depression <0.05 mV and minimally inversion
      (<0.03 mV) of T wave were found on 53.8% and 23.1% of resting ECG, respectively.
      53.8% of patients had the family history of CAD. 73.1% of subjects were
      overweight. Family history was correlated with CAD and its type (p=0.023). 76.9%
      and 23.1% of the subjects had equivocal and positive result on TT, respectively.
      Presence of hypertension, hyperlipidemia, and smoking were lower and diabetes was
      absent. Additionally, subjects with two or more vessel disease were observed
      slightly older compared to those with one vessel disease (45.5+/-3.8 vs. 42.2+/
      5.5, p=0.101). CONCLUSION: Aircrew >=40 years old, with family history, ST/T
      changes on resting ECG, and equivocal results on TT even in the absence of
      multiple coronary risk factors may need further cardiovascular tests. MSCT is an
      effective and noninvasive way of detection of CAD in aircrew when needed.

PMID- 24449630
TI  - Role of clinical features in prediction of coronary artery disease documented by
      multi-slice CT angiography in aviation.

PMID- 24449631
TI  - The effects of iodixanol and iopamidol on adhesion molecule serum levels in
      patients with angina pectoris undergoing coronary angiography: a randomized
      study.
AB  - OBJECTIVE: To compare intercellular adhesion molecule-1 (ICAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) serum levels between patients with stable (SAP)
      and unstable angina pectoris (USAP) undergoing coronary angiography (CAG),
      investigate effects of CAG on ICAM-1, VCAM-1 levels in SAP, USAP patients;
      probable different effects of non-ionic radiocontrast media (RCM), iso-osmotic
      iodixanol and low osmolar iopamidol, on these adhesion molecules (AM). METHODS:
      In this randomized, prospective study, 2 groups consisting of patients with SAP
      (n=22) and USAP (n=22) undergoing CAG were included. For halves of each group
      iopamidol, for the other halves iodixanol were used as RCM, in turn for
      randomization. The patients were divided into 4 subgroups according to clinical
      presentations and used RCM(SAP-iodixanol, SAP-iopamidol USAP-iodixanol, USAP
      iopamidol). ICAM-1, VCAM-1 levels were measured just before and 12 hours after
      CAG. Repeated measurements were compared with two-way ANOVA test. RESULTS:
      Baseline VCAM-1 concentration was higher in USAP group than SAP group (p=0.001).
      ICAM-1, VCAM-1 concentrations increased significantly following CAG in SAP, USAP
      groups. ICAM-1, VCAM-1 concentration increments; didn't reach statistical
      significance in SAP-iodixanol subgroup, reached a borderline significance in SAP
      iopamidol subgroup (p=0.06). In USAP-iodixanol subgroup; only VCAM-1 (p<0.001),
      in USAP-iopamidol subgroup; ICAM-1 (p=0.009), VCAM-1 (p=0.006) levels increased
      significantly following CAG. No complication was observed. CONCLUSION: To our
      knowledge, this is the first study indicating ICAM-1, VCAM-1 inducing effect of
      CAG in patients with SAP, USAP and differential effects of iodixanol and
      iopamidol on ICAM-1, VCAM-1 serum levels. Further studies are needed to clarify
      the effects of CAG and different RCM on vascular inflammation, vessel injury,
      serum AM levels and their clinical significance. This study should be taken as a
      pilot, hypothesis-generating study.

PMID- 24449632
TI  - Clinical outcome, pain perception and activities of daily life after minimally
      invasive coronary artery bypass grafting.
AB  - OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) for
      revascularization of the left anterior descending artery has become a routine
      operation. We present our clinical experiences with beating heart MIDCAB surgery
      performed through partial lower sternotomy (PLS) and retrospectively compare the
      results of pain perception as well as activities of daily life (ADL) with the
      conventional full sternotomy. METHODS: From January 2009 to August 2012, 197
      patients underwent MIDCAB using modified PLS at our hospital. Their mean age was
      58.5+/-10.5 years. 54 (28%) had previous myocardial infarction, 38 (19%) had
      diabetes mellitus. The visual analog scale (VAS) for pain one, two and three, the
      ADL score for mobilization were obtained within four days after surgery. 98% of
      patients were followed-up with both direct visits and questionnaires to assess
      the major adverse cardiac events (MACE). We performed t-test for comperative data
      and Kaplan-Meier curves for survival analysis. RESULTS: There was one
      postoperative death (0.5%) and three conversions to full sternotomy (1.5%).
      Postoperative angiography was performed in 34 (17.2%) patients, who had some
      symptoms during the follow-up period of 45 months. The graft patency rate was
      96.5% (190 of 197). At follow-up (24.1+/-11.7 months), survival free of MACE was
      91.8+/-3.1% at 3.5 years. Both the Visual Analog Scale (35.1+/-9.6 vs. 57.1+/
      7.8) and the ADL score (80.4+/-11.8 vs. 36.2+/-8.6) were significantly higher
      after the operation in comparison to the matched group of beating heart
      revascularizations with full sternotomy (p<0.001). CONCLUSION: This study
      demonstrates that the MIDCAB using PLS can achieve an effective intermediate-term
      revascularization and an acceptable clinical outcome. Patients who undergo this
      procedure are free of major complications and enjoy good quality of life after
      surgery.

PMID- 24449633
TI  - The QT prolongation and clinical features in patients with takotsubo
      cardiomyopathy: Experiences of two tertiary cardiovascular centers.
AB  - OBJECTIVE: There are few data regarding clinical characteristics, laboratory
      parameters, electrocardiographic and echocardiographic findings in takotsubo
      cardiomyopathy patients presenting with QT prolongation. Aim of this study was to
      investigate the differences in these parameters between takotsubo cardiomyopathy
      patients presenting with and those without QT prolongation. METHODS: We performed
      an observational retrospective study. One hundred five patients were enrolled
      from the takotsubo cardiomyopathy registry database and divided according to the
      presence of QT prolongation. Fifty patients presented with QT prolongation (QT
      group) and 55 did not (NQT group). Statistical analysis was performed using
      Student's t-test or Mann-Whitney U test and chi-square test. RESULTS: QT group
      had higher prevalence of dyspnea (66 versus 40%, p=0.008) and cardiogenic shock
      (46 versus 24%, p=0.016) than NQT group. QT group had higher prevalence of ST
      elevation (82 versus 64%, p=0.036), T wave inversion (96 versus 58%, p=0.001),
      ventricular tachycardia/ventricular fibrillation (8 versus 0%, p=0.032) and
      classic ballooning pattern (92 versus 66%, p=0.003), but lower left ventricular
      ejection fraction (mean, 39.2 versus 43.5%, p=0.005). In addition, QT group had
      significant higher hs-C-reactive protein (median, 6.6 versus 1.7 mg/L, p=0.023),
      creatine kinase-MB (median, 18.6 versus 7.6 ng/mL, p=0.032) and NT-pro-brain
      natriuretic peptide levels (median, 3637 versus 2145 pg/mL, p=0.044). QT group
      required more frequent use of inotropics (46 versus 24%, p=0.016) and diuretics
      (58 versus 38%, p=0.042) than NQT group. CONCLUSION: The clinical features of
      takotsubo cardiomyopathy are different according to the presence of QT
      prolongation. The QT group was lesser likely to have preserved cardiovascular
      reserve and more likely to require hemodynamic support than the NQT group despite
      the entire prognosis of takotsubo cardiomyopathy is excellent regardless of QT
      prolongation.

PMID- 24449634
TI  - Prognostic impact of QT intervals in takotsubo cardiomyopathy: still a long way
      to trap the octopus.

PMID- 24449635
TI  - Safety and efficacy of topical bacteriophage and ethylenediaminetetraacetic acid
      treatment of Staphylococcus aureus infection in a sheep model of sinusitis.
AB  - BACKGROUND: Treatment of sinonasal bacterial biofilms continues to be a challenge
      in modern rhinology. This study's objective was to assess the safety and efficacy
      of topically applied Cocktail of S. aureus specific phage (CTSA) alone and in
      combination with ethylenediaminetetraacetic acid (EDTA) for treatment of
      Staphylococcus aureus biofilms in vivo. METHODS: Using a sheep model of
      sinusitis, frontal sinuses (n = 6 per treatment) were flushed once daily with a
      CTSA (2 * 10(6) plaque forming units [PFU]/mL), with or without EDTA (0.075
      mg/mL), and compared to a control flush containing saline and heat-inactivated
      CTSA. Safety was assessed using histology and scanning electron microscopy (SEM)
      after treatment for 3 days. Efficacy was assessed by quantifying the generation
      of S. aureus biofilms in the frontal sinuses after 5 days of treatment. Biofilm
      mass was compared between treatment groups and controls using LIVE/DEAD BacLight
      staining and confocal scanning laser microscopy to visualize the tissue sections.
      COMSTAT2 software was used to compute the biofilm mass present on tissue
      sections. RESULTS: Tissue morphology was conserved, with no significant signs of
      inflammation, when comparing control and test treatments. Furthermore, SEM
      analysis indicated test treatments were not toxic or damaging to mucosal cilia.
      COMSTAT2 quantification of biofilm showed a significant reduction in biofilm
      levels when comparing the control with CTSA (p = 0.0043), EDTA (p = 0.0095), and
      CTSA-EDTA (p = 0.0022) treatments. CONCLUSION: Results indicate that CTSA and
      EDTA are safe and efficacious for short-term topical application against S.
      aureus infection in a sheep sinusitis model, and have the potential to be
      translated to a clinical setting.

PMID- 24449636
TI  - Highly crystallized nanometer-sized zeolite a with large Cs adsorption capability
      for the decontamination of water.
AB  - Nanometer-sized zeolite A with a large cesium (Cs) uptake capability is prepared
      through a simple post-milling recrystallization method. This method is suitable
      for producing nanometer-sized zeolite in large scale, as additional organic
      compounds are not needed to control zeolite nucleation and crystal growth.
      Herein, we perform a quartz crystal microbalance (QCM) study to evaluate the
      uptake ability of Cs ions by zeolite, to the best of our knowledge, for the first
      time. In comparison to micrometer-sized zeolite A, nanometer-sized zeolite A can
      rapidly accommodate a larger amount of Cs ions into the zeolite crystal
      structure, owing to its high external surface area. Nanometer-sized zeolite is a
      promising candidate for the removal of radioactive Cs ions from polluted water.
      Our QCM study on Cs adsorption uptake behavior provides the information of
      adsorption kinetics (e.g., adsorption amounts and rates). This technique is
      applicable to other zeolites, which will be highly valuable for further
      consideration of radioactive Cs removal in the future. 

PMID- 24449637
TI  - High-throughput miniaturized bioreactors for cell culture process development:
      reproducibility, scalability, and control.
AB  - Decreasing the timeframe for cell culture process development has been a key goal
      toward accelerating biopharmaceutical development. Advanced Microscale
      Bioreactors (ambrTM) is an automated micro-bioreactor system with miniature
      single-use bioreactors with a 10-15 mL working volume controlled by an automated
      workstation. This system was compared to conventional bioreactor systems in terms
      of its performance for the production of a monoclonal antibody in a recombinant
      Chinese Hamster Ovary cell line. The miniaturized bioreactor system was found to
      produce cell culture profiles that matched across scales to 3 L, 15 L, and 200 L
      stirred tank bioreactors. The processes used in this article involve complex feed
      formulations, perturbations, and strict process control within the design space,
      which are in-line with processes used for commercial scale manufacturing of
      biopharmaceuticals. Changes to important process parameters in ambrTM resulted in
      predictable cell growth, viability and titer changes, which were in good
      agreement to data from the conventional larger scale bioreactors. ambrTM was
      found to successfully reproduce variations in temperature, dissolved oxygen (DO),
      and pH conditions similar to the larger bioreactor systems. Additionally, the
      miniature bioreactors were found to react well to perturbations in pH and DO
      through adjustments to the Proportional and Integral control loop. The data
      presented here demonstrates the utility of the ambrTM system as a high throughput
      system for cell culture process development.

PMID- 24449638
TI  - Backward position shift in apparent motion.
AB  - We investigated the perceived position of visual targets in apparent motion. A
      disc moved horizontally through three positions from -10 degrees  to +10 degrees 
      in the far periphery (20 degrees  above fixation), generating a compelling
      impression of apparent motion. In the first experiment, observers compared the
      position of the middle of the three discs to a subsequently presented reference.
      Unexpectedly, observers judged its position to be shifted backward, in the
      direction opposite that of the motion. We then tested the middle disc in
      sequences of 3, 5, and 7 discs, each covering the same spatial and temporal
      extents (similar speeds). The backwards shift was only found for the three-disc
      sequence. With the extra discs approaching more continuous motion, the perceived
      shift was in the same direction as the apparent motion. Finally, using a
      localization task with constant static references, we measured the position
      shifts of all the disc locations for two-disc, three-disc and four-disc apparent
      motion sequences. The backward shift was found for the second location of all
      sequences. We suggest that the backward shift of the second element along an
      apparent motion path is due to an attraction effect induced by the initial point
      of the motion. 

PMID- 24449647
TI  - Experimental psychology: toward reproducible research.

PMID- 24449648
TI  - How automatic is the musical stroop effect? Commentary on "the musical stroop
      effect: opening a new avenue to research on automatisms" by l. Gregoire, P.
      Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp.
      269-278).
AB  - Gregoire, Perruchet, and Poulin-Charronnat (2013) investigated a musical variant
      of the reversed Stroop effect. According to the authors, one big advantage of
      this variant is that the automaticity of note naming can be better controlled
      than in other Stroop variants as musicians are very practiced in note reading
      whereas non-musicians are not. In this comment we argue that at present the exact
      impact of automaticity in this Stroop variant remains somewhat unclear for at
      least three reasons, namely due to the type of information that is automatically
      retrieved when notes are encountered, due to the possible influence of object
      based attention, and finally due to the fact that the exact influence of
      expertise on interference cannot be pinpointed with an extreme group design. 

PMID- 24449649
TI  - What is learned, and when? Commentary on "the musical stroop effect: opening a
      new avenue to research on automatisms" by l. Gregoire, P. Perruchet, and B.
      Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269-278).
AB  - In the musical Stroop task, which has recently been introduced by Gregoire,
      Perruchet, and Poulin-Charronat (2013), participants respond to note names that
      are placed inside musical notes. Musicians respond more slowly to note names that
      are incongruent with the note than to note names that are congruent with the
      note. Gregoire et al. propose to use this task to study the acquisition of
      automaticity by relating musical Stroop effects to the amount of musical
      experience. I discuss some caveats that have to be considered for these types of
      analyses. Specifically, I focus on how different contingencies in the learning
      situation relate to the Stroop effect and on the question whether a long-term
      perspective is suitable for studying the acquisition of automaticity. 

PMID- 24449650
TI  - Additional insights. Commentary on "the musical stroop effect: opening a new
      avenue to research on automatisms" by l. Gregoire, P. Perruchet, and B. Poulin
      Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269-278).
AB  - In their paper "The Musical Stroop Effect: Opening a New Avenue to Research on
      Automatisms," <citationReference id="cr4-1" rid="c4">Gregoire, Perruchet, and
      Poulin-Charronnat (2013)</citationReference> use a musical Stroop-like task to
      demonstrate the automaticity of musical note naming in musicians. In addition,
      the authors suggest that music training can serve as a tool in order to study the
      acquisition of automaticity. In the following commentary, we aim to address three
      main issues concerning the paper by <citationReference id="cr4-2"
      rid="c4">Gregoire et al. (2013)</citationReference>. First, we will suggest some
      additional interpretations of the results; specifically, we will relate to the
      association between music and space. Second, we will discuss a methodological
      issue dealing with interference, facilitation, and the role of the neutral
      condition. We suggest that the study by <citationReference id="cr4-3"
      rid="c4">Gregoire et al. (2013)</citationReference> lacks a proper neutral
      condition and thus it is impossible to assert that the congruency effect is
      interference based. Third, we will discuss the authors' suggestion of using the
      musical Stroop effect as a tool for studying automatism. We consider the
      practical relevance of music training as a tool for studying the acquisition of
      automaticity by pointing out that music training is highly heterogeneous. 

PMID- 24449651
TI  - Can the "musical stroop" task replace the classical stroop task? Commentary on
      "The musical Stroop effect: Opening a new avenue to research on automatisms" by
      l. Gregoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology,
      2013, vol. 60, pp. 269-278).
AB  - The musical Stroop task is analyzed and compared to the classical Stroop task.
      The analysis indicates that the two tasks differ in the following significant
      characteristics: ecological validity, the interrelations between the two
      perceptual dimensions involved, the nature of the automatic process and the
      existence of a potential Garner interference. It is concluded that the musical
      task has no advantage over the classical task. 

PMID- 24449652
TI  - Is the musical stroop effect able to keep its promises? A reply to Akiva-Kabiri
      and Henik (2014), Gast (2014), Moeller and Frings (2014), and Zakay (2014).
AB  - Gregoire, Perruchet, and Poulin-Charronnat (2013) claimed that the Musical Stroop
      task, which reveals the automaticity of note naming in musician experts, provides
      a new tool for studying the development of automatisms through extensive training
      in natural settings. Many of the criticisms presented in the four commentaries
      published in this issue appear to be based on a misunderstanding of our
      procedure, or questionable postulates. We maintain that the Musical Stroop Effect
      offers promising possibilities for further research on automaticity, with the
      main proviso that the current procedure makes it difficult to tease apart
      facilitation and interference. 

PMID- 24449653
TI  - Ca2+ signal transduction related to neutral lipid synthesis in an oil-producing
      green alga Chlorella sp. C2.
AB  - Changes in the cytosolic Ca(2+) levels and the role of Ca(2+) signal transduction
      in neutral lipid synthesis in Chlorella sp. C2 under nitrogen starvation
      conditions were investigated. The results detected by using the scanning ion
      selective electrode technique demonstrate that nitrogen starvation induced
      significant Ca(2+) influx across the plasma membrane into cells. Ca(2+)
      fluorescence imaging and flow cytometry were used to estimate the effect of this
      Ca(2+) influx on the generation of the Ca(2+) signal, and the results showed that
      the cytosolic Ca(2+) concentration increased transiently and then remained at a
      stable, high level when the cells were exposed to nitrogen starvation. However,
      the increase could be inhibited by pre-treatment with the Ca(2+) channel blockers
      ruthenium red, verapamil and GdCl3, indicating that both the influx of Ca(2+)
      from the extracellular space via Ca(2+) channels that are localized in the plasma
      membrane and the release of Ca(2+) from intracellular calcium storage via the
      internal calcium store were required for the generation and transduction of the
      Ca(2+) signal. During nitrogen starvation, neutral lipid synthesis in Chlorella
      sp. C2 in response to stress conditions was also inhibited to differing degrees
      by pre-treatment with the three Ca(2+) channel blockers, demonstrating the
      regulation of Ca(2+) via these Ca(2+) channels in neutral lipid synthesis. The
      results suggested that by transduction of extracellular stress signals into the
      cell and the regulation of the Ca(2+) signal in neutral lipid synthesis, Ca(2+)
      signal transduction played important roles in the response mechanism of Chlorella
      sp. C2 to nitrogen starvation. 

PMID- 24449654
TI  - GluTR2 complements a hema1 mutant lacking glutamyl-tRNA reductase 1, but is
      differently regulated at the post-translational level.
AB  - Arabidopsis HEMA1 and HEMA2 encode glutamyl-tRNA reductase (GluTR) 1 and 2, the
      two isoforms of the initial enzyme of tetrapyrrole biosynthesis. HEMA1 is
      dominantly expressed in photosynthetic tissue, while HEMA2 shows low constitutive
      expression and is induced upon stress treatments. We introduce a new HEMA1
      knockout mutant which grows only heterotrophically on MS (Murashige and Skoog)
      medium at low light, indicating that the remaining GluTR2 does not sufficiently
      compensate for the extensive needs of metabolic precursors for Chl. While hema1
      accumulates low amounts of Chl, it contains more than half of the wild-type heme
      content. The functional diversity of the two GluTR isoforms was analyzed by means
      of complementation studies of the hema1 mutant by expression of pHEMA1::HEMA2 and
      p35S::HEMA1, respectively. Expression of both transgenes complements hema1,
      indicating that GluTR2 can likewise be involved in the synthesis of Chl and is
      not exclusively assigned to heme synthesis. In comparison with p35S::HEMA1
      complemented hema1 and the wild type, GluTR2 expression under control of the
      HEMA1 promoter (pHEMA1) in pHEMA1::HEMA2-complemented hema1 mutants causes
      elevated protochlorophyllide levels under extended dark periods as well as in
      short-day-grown adult plants, resulting in the formation of necrotic leaf tissue.
      Although both GluTR isoforms have similar activity and contribute to 5
      aminolevulinic acid synthesis for adequate accumulation of Chl and heme, it is
      proposed that the two proteins experience a different post-translational control
      in darkness and light. While GluTR2 continues 5-aminolevulinic acid synthesis in
      darkness, GluTR1 is efficiently inactivated by the interaction with the FLU
      (FLUORESCENT) protein, thereby preventing an accumulation of protochlorophyllide.

PMID- 24449656
TI  - Partition behavior of CD133(+) stem cells from human umbilical cord blood in
      aqueous two-phase systems: In route to establish novel stem cell primary recovery
      strategies.
AB  - Aqueous two-phase systems (ATPS) represent a promising strategy for the recovery
      of CD133(+) stem cells. This particular type of stem cells has great potential
      for research and clinical applications. Traditional [polyethylene glycol (PEG),
      dextran (DEX), and ficoll] and novel (Ucon) polymer-polymer ATPS were exploited
      to study the partitioning behavior of CD133(+) stem cells and contaminants from
      human umbilical cord blood (HUCB). The aim of the study was to select conditions
      under which the product of interest and the contaminants concentrate in opposite
      phases. To accomplish this, three independent samples were tested: (1) enriched
      CD133(+) sample, (2) whole HUCB (contaminants), and (3) complex sample (CD133(+)
      stem cells and contaminants). The objective of this research was to evaluate the
      partition behavior of CD133(+) in ATPS in route to establish the basis for the
      development of a novel and scalable purification bioprocess. In conclusion, the
      partitioning behavior of CD133(+) stem cells and contaminants from complex
      samples was as follows: 59% of CD133(+) stem cells fractionated to the top phase
      when employing ficoll 400,000-DEX 70,000 or 100% to the bottom phase with Ucon
      DEX 75,000 and PEG 8,000-DEX 500,000 ATPS. In average, 35% of the contaminants
      partitioned to the top phase of the ficoll 400,000-DEX 70,000 ATPS, 99% to the
      dextran rich phase of the Ucon-DEX 75,000 systems and 97% to the bottom phase of
      the PEG 8,000-DEX 500,000. Cell viability was at least 98% after ATPS recovery.

PMID- 24449655
TI  - Conductive olfactory losses in chronic rhinosinusitis? A computational fluid
      dynamics study of 29 patients.
AB  - BACKGROUND: Besides sensorineural factors, conductive impediments likely
      contribute to olfactory losses in chronic rhinosinusitis (CRS) patients, yet no
      conclusive evidence exists. We aimed to examine possible conductive factors using
      computational fluid dynamics (CFD) models. METHODS: A total of 29 CRS patients
      were assessed via odorant detection thresholds (ODTs), rhinomanometry (nasal
      resistance [NR]), acoustic rhinometry (minimum-cross-sectional area [MCA]) and
      computed tomography (CT) staging. CFD simulations of nasal airflow and odorant
      absorption to olfactory region were carried out based on individual CTs. Biopsies
      of olfactory epithelium (OE) were collected, cryosectioned, stained, and scored
      for erosion. RESULTS: Significant correlations to ODTs were found for 3
      variables: odor absorption in the olfactory region (r = -0.60, p < 0.01), MCA (r
      = -0.40, p < 0.05), and CT staging (r = 0.42, p < 0.05). However, significant
      findings were limited to ODTs of the highly soluble l-carvone. Multiple
      regression analysis revealed that these variables combined, with the addition of
      NR, can account for 65% of the total variance in ODTs. CT staging correlated
      significantly with OE erosion (r = 0.77, p < 0.01) and can replace the latter in
      the regression with comparable outcomes. Partial correlations suggest the
      contributions of both conductive and sensorineural variables are more prominent
      if adjusted for the effects of the other. Olfactory loss and inflammatory factors
      have strong bilateral involvement, whereas conductive factors are independent
      between sides. As validation, CFD-simulated NRs significantly correlated with
      rhinomanometrically assessed NRs (r = 0.60, p < 0.01). CONCLUSION: Both
      conductive and sensorineural mechanisms can contribute to olfactory losses in
      CRS. CFD modeling provides critical guidance in understanding the role of
      conductive impediments in olfactory dysfunction in CRS.

PMID- 24449657
TI  - Gas sorption studies on a microporous coordination polymer assembled from 2D grid
      layers by strong pi-pi interactions.
AB  - The microporous coordination polymer [Co(H2 L)(bipy)0.5 ]?2 H2 O (1, bipy=4,4'
      bipyridine) was synthesized on the basis of the V-shaped flexible diphosphonate
      ligand (2,4,6-trimethyl-1,3-phenylene)bis(methylene)diphosphonic acid (H4 L) and
      the auxiliary bipy ligand under hydrothermal conditions. The structure of this
      compound was characterized by single-crystal X-ray diffraction. By joining the
      diphosphonate ligands and bipy through tetrahedral [CoO3 N] clusters, a 2D square
      grid layered network was formed. Further stacking of these layers on the basis of
      pi-pi interactions resulted in a pseudo-3D microporous network with 1D channels
      running through the a axis. Gas sorption studies for CO2 , H2 , CH4 , N2 , and O2
      on this coordination polymer were performed, and the results revealed interesting
      dynamic and hysteresis sorption behavior toward H2 at low temperature. 

PMID- 24449658
TI  - Referral patterns for endocrine surgical disease.
AB  - OBJECTIVE: Referrals between physician specialties are common practice, and clear
      patterns develop. The increasing availability of high-volume endocrine surgery
      subspecialists with better outcomes may change these patterns. This study aimed
      to determine what factors influence endocrinologists' referral patterns for the
      surgical treatment of endocrine disease. METHODS: A national, cross-sectional,
      voluntary survey of members of the American Association of Clinical
      Endocrinologists examined physician demographics, physician's opinions on
      referral to endocrine surgery, preferred surgeon specialty, knowledge about
      surgeon characteristics, and how these factors influenced which surgeons they
      referred patients, as well as what changes in these factors would alter their
      referral patterns. RESULTS: The survey response rate was 15% (73/500), and 97%
      were endocrinologists. On average, 0 to 5 patients/week were referred for
      surgery. Most respondents (91.8%) felt that endocrinologists should decide which
      surgeon to refer. General surgery was the preferred surgeon specialty (43.7%),
      and endocrine surgery was the preferred subspecialty (70.8%). The factors most
      often cited as very important in referral to a surgeon included surgeon
      outcome/complications (71%), familiarity with surgeon (65%), surgeon's
      communication with referring physician (61%), and surgeon volume (59%). The
      factors most often cited as likely to change physician referral patterns included
      patient satisfaction (62%), complication rates (57%), surgeon outcomes (54%), and
      surgeon volume (50%). The factors most often cited as unlikely to change referral
      patterns included new surgeon availability (70%) and hospital/surgeon advertising
      (58%). CONCLUSION: Referring physicians want experienced endocrine surgeons with
      high operative volumes and good outcomes whom they are familiar with. The
      promotion of referral to high-volume surgeons requires communication, good
      outcomes, and satisfied patients.

PMID- 24449659
TI  - Bilateral ovary adrenal rest tumor in a congenital adrenal hyperplasia following
      adrenalectomy.
AB  - OBJECTIVE: In contrast to the high incidence of testicular adrenal rest tumors in
      adult male patients with congenital adrenal hyperplasia (CAH), ovarian adrenal
      rest tumors (OARTs) in female CAH patients are rare. In this case report, we
      describe a case of bilateral OART in a female patient with CAH due to 21
      hydroxylase deficiency. METHODS: We present a detailed case report with the
      clinical, imaging, and laboratory findings of the patient. The pertinent
      literature is also reviewed. RESULTS: A 17-year-old patient was known to have CAH
      due to 21-hydroxylase deficiency. Since the second month of her gestational age,
      her mother was treated with cortisone-replacement therapy. The patient was
      treated with hydrocortisone and fludrocortisone since the neonatal period. Her
      pertinent history included a bilateral adrenalectomy at the age of 13 years in
      2006, and for 3 years she led a normal puberty life with no complaint with
      hormonal replacement therapy. Nevertheless, in 2009, she developed a virilizing
      syndrome. Subsequently, she underwent surgery in December 2009 for right
      adnexectomy. However, the regression of the masculinizing mass was not complete
      and worsened several months after the surgery. A new pelvic magnetic resonance
      image showed the activation of a contralateral ovarian mass, necessitating a left
      adnexectomy in August 2010. CONCLUSION: This case demonstrates some interesting
      features of OART that pose challenges to its management. If an OART is detected
      early enough and glucocorticoid therapy is received, it is possible that the OART
      will decrease in size following suppression of adrenocorticotropic hormone
      levels.

PMID- 24449660
TI  - Aerobic fitness and glycemic variability in adolescents with type 1 diabetes.
AB  - OBJECTIVE: This study examines the association of fitness on glycemic variability
      (GV) in adolescents with type 1 diabetes mellitus (T1DM). GV has been associated
      with high frequency of hyper- and hypoglycemia. METHODS: Nineteen adolescents
      with T1DM, ages 14 to 19 years, underwent aerobic fitness testing to determine
      their maximal aerobic capacity (VO2 max). A continuous glucose monitoring (CGM)
      device was placed on each subject and worn for 3 to 5 days until a return visit
      when the subjects underwent a 1-hour treadmill exercise session. Mean amplitude
      of glycemic excursion (MAGE) was calculated from the CGM data collected between
      the 2 study visits. Metabolic equivalent (MET), a measure of accumulated
      metabolic workload during the exercise session, was also calculated. RESULTS:
      Mean VO2 max was 46.6 +/- 6.8 mL/kg/min, with a range of 34.8 to 57.0 mL/kg/min.
      Mean MET during the exercise session was 577.2 +/- 102.4 and ranged from 354.3 to
      716.2 METs. There was an inverse association between VO2 max and MAGE (r = -0.46;
      95% confidence interval [CI], -0.01 to -0.76; P = .048). MET load and MAGE also
      had an inverse relationship (r = -0.48; 95% CI, -0.03 to -0.77; P = .037).
      CONCLUSION: GV is inversely associated with fitness and MET load. Aerobic fitness
      should be promoted in adolescents with T1DM not only because of its multiple
      beneficial effects but also due to a possible association with GV, leading to
      fewer extremes in hypo- and hyperglycemia.

PMID- 24449661
TI  - Hypercalcemia and acromegaly--clarifying the connections. A case report and
      review of the literature.
AB  - OBJECTIVE: Hypercalcemia in patients with acromegaly is rare and usually due to
      co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly
      related to acromegaly is debated. METHODS: We present a case report of
      1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss
      potential pathophysiological mechanisms contributing to the development of
      hypercalcemia late in the course of the disease. RESULTS: A 67-year-old female
      presented with classical features of acromegaly. A review of her previous
      photographs suggested a disease duration of approximately 10 years, and her serum
      calcium (Ca) was normal during this period. A biochemical work up confirmed a
      combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH
      level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1)
      level of 1,498 ng/mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic
      resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her
      preoperative work up revealed new onset hypercalcemia with a corrected serum Ca
      level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a
      parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3
      level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma
      with normalization of GH and PRL levels, and her IGF-1 level decreased to 304
      ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6
      pg/mL) normalized after surgery. CONCLUSION: While overt hypercalcemia in
      acromegaly is rare, it tends to occur late in the disease course. The
      hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH.

PMID- 24449662
TI  - Genetics, diagnosis, and management of medullary thyroid carcinoma and
      pheochromocytoma/paraganglioma.
AB  - OBJECTIVE: Medullary thyroid carcinoma (MTC) and pheochromocytoma/paraganglioma
      (PHEO/PGL) are rare neuroendocrine tumors. Because of the increased metastatic
      rates in certain genetic backgrounds, early diagnosis and treatment are essential
      to improved patient outcomes. Our objective was to summarize recent findings
      related to the genetics, diagnosis, and management of MTC and PHEO/PGL. METHODS:
      A literature review was performed. RESULTS: MTC is primarily associated with
      mutations in the rearranged during transfection (RET) proto-oncogene. Determining
      the specific genetic mutation can guide patient management and screening. Early
      detection and appropriate surgical management of MTC is critical to prevent or
      limit metastatic spread, as treatment options for patients with metastatic
      disease are limited. PHEO/PGL also has a strong genetic component, with
      approximately 50% of cases linked to germline and somatic mutations in 15 genes.
      Although most PHEO/PGLs are benign, factors such as genetic background, size,
      tumor location, and high methoxytyramine levels are associated with higher rates
      of metastatic disease. The state-of-the-art diagnosis and localization of
      PHEO/PGLs is based on measurement of plasma metanephrines and methoxytyramine and
      functional imaging studies. For both PHEO/PGL and MTC, surgery is the only
      curative treatment. Treatment options for patients with metastatic disease are
      limited. CONCLUSION: As genetic testing becomes more widely available, the
      diagnosis of MTC and PHEO/PGL will be made earlier due to routine screening of at
      risk patients. In addition, continued advances in basic science, diagnostic
      methods, and imaging techniques will improve understanding of the pathogenesis of
      these diseases and facilitate the introduction of novel treatment strategies for
      patients with metastatic disease.

PMID- 24449664
TI  - Understanding the burden of illness associated with hypoparathyroidism reported
      among patients in the PARADOX study.
AB  - OBJECTIVE: Hypoparathyroidism is a rare disease caused by lack of parathyroid
      hormone (PTH) leading to hypocalcemia, hyperphosphatemia, and a variety of
      symptoms. This study aimed to quantify the clinical and social burden of illness
      from the perspective of affected patients. METHODS: A web-based instrument was
      developed with input from patients, clinical experts, and the Hypoparathyroidism
      Association. Qualifying participants were >=18 years old, diagnosed with
      hypoparathyroidism for >=6 months, and U.S. residents. Questions focused on
      demographics, diagnosis perceptions, current attitudes, medical management,
      current symptoms, acute episodes, comorbidities, personal life, and employment.
      RESULTS: A total of 374 adults (mean age, 49 +/- 12 years; female, 85%) with
      hypoparathyroidism (mean duration, 13 +/- 12 years; severe condition, 30.5%)
      completed the survey. Patients reported visiting a mean of 6 +/- 8 physicians
      before and after their diagnosis. The majority strongly agreed with feeling
      unprepared to manage the condition at diagnosis (56%), that controlling their
      hypoparathyroidism is harder than expected (60%), and that they were concerned
      about long-term complications of their current medications (75%). More than 10
      symptoms were experienced by 72% of patients in the preceding 12 months, despite
      current management regimens. Symptoms were experienced for a mean of 13 +/- 9
      hours/day. Hospital stays or emergency department visits were required by 79% of
      patients. 45% reported significant interference with their lives, 85% reported an
      inability to perform household activities, and 20% experienced a disease
      associated change in employment status. CONCLUSION: Patients with
      hypoparathyroidism have a high burden of illness and experience a broad spectrum
      of symptoms, with a multidimensional impact on their lives.

PMID- 24449663
TI  - Association Between Thyroid Function and Objective and Subjective Sleep Quality
      in Older Men: The Osteoporotic Fractures in Men (MrOS) Study.
AB  - OBJECTIVE: To determine the association between thyroid hormone levels and sleep
      quality in community-dwelling men. METHODS: Among 5,994 men aged >=65 years in
      the Osteoporotic Fractures in Men (MrOS) study, 682 had baseline thyroid function
      data, normal free thyroxine (FT4) (0.70 <= FT4 <= 1.85 ng/dL), actigraphy
      measurements, and were not using thyroid-related medications. Three categories of
      thyroid function were defined: subclinical hyperthyroid (thyroid-stimulating
      hormone [TSH] <0.55 mIU/L), euthyroid (TSH, 0.55 to 4.78 mIU/L), and subclinical
      hypothyroid (TSH >4.78 mIU/L). Objective (total hours of nighttime sleep [TST],
      sleep efficiency [SE], wake after sleep onset [WASO], sleep latency [SL], number
      of long wake episodes [LWEP]) and subjective (TST, Pittsburgh Sleep Quality Index
      score, Epworth Sleepiness Scale score) sleep quality parameters were measured.
      The association between TSH and sleep quality was examined using linear
      regression (continuous sleep outcomes) and log-binomial regression (categorical
      sleep outcomes). RESULTS: Among the 682 men examined, 15 had subclinical
      hyperthyroidism and 38 had subclinical hypothyroidism. There was no difference in
      sleep quality between subclinical hypothyroid and euthyroid men. Compared to
      euthyroid men, subclinical hyperthyroid men had lower mean actigraphy TST
      (adjusted mean difference [95% confidence interval (CI)], -27.4 [-63.7 to 8.9]
      minutes), lower mean SE (-4.5% [-10.3% to 1.3%]), and higher mean WASO (13.5 [
      8.0 to 35.0] minutes]), whereas 41% had increased risk of actigraphy-measured TST
      <6 hours (relative risk [RR], 1.41; 95% CI, 0.83 to 2.39), and 83% had increased
      risk of SL >=60 minutes (RR, 1.83; 95% CI, 0.65 to 5.14) (all P>.05). CONCLUSION:
      Neither subclinical hypothyroidism nor hyperthyroidism is significantly
      associated with decreased sleep quality.

PMID- 24449665
TI  - Vitamin D, parathyroid hormone, and serum lipid profiles in a middle-aged and
      elderly Chinese population.
AB  - OBJECTIVES: To explore the associations of serum vitamin D and parathyroid
      hormone (PTH) levels with serum lipid profiles and the risk of hyperlipidemia in
      a middle-aged and elderly population. METHODS: A population-based cross-sectional
      study was conducted in the spring of 2012 among 1,203 Chinese participants, aged
      52 to 101 years. 25-Hydroxyvitamin D [25(OH)D] was measured by chemiluminescence
      assay. (PTH) levels were measured with an electrochemiluminescence immunoassay
      (ECLIA) method. RESULTS: A total of 1,203 participants, including 526 women
      (43.7%), were evaluated in 2012. The median concentrations of serum 25(OH)D and
      PTH for the entire group were 17.3 ng/mL and 38.3 pg/mL, respectively. Serum
      25(OH)D and PTH levels were not independently associated with serum total
      cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high
      density lipoprotein (HDL) cholesterol levels in a multivariate adjusted linear
      regression analysis of 1,027 participants not receiving antihyperlipidemic
      treatment (P>.05). In logistic regression analyses, serum 25(OH)D and PTH levels
      were not associated with a risk of hyperlipidemia after adjustment for age, sex,
      heavy drinking, smoking, diabetes, obesity, family history of hyperlipidemia,
      body mass index (BMI), physical activity, glomerular filtration rate (GFR),
      fasting glucose, high-sensitivity C-reactive protein (hsCRP), calcium, and
      hemoglobin. CONCLUSIONS: Serum 25(OH)D and PTH levels are not independently
      associated with serum lipid levels or an increased risk of hyperlipidemia in a
      middle-aged and elderly Chinese population.

PMID- 24449666
TI  - How well do self-monitored capillary glucose measurements predict the mean blood
      glucose from 24-hour continuous monitoring in endocrine practice?
AB  - OBJECTIVE: The mean blood glucose (MBG) level obtained from self-monitored
      capillary glucose (SMCG) data is a readily available metric of glycemic control
      for patients and their physicians. However, whether there is agreement between
      SMCG MBG levels and MBG levels obtained from 24-hour intensive glucose sampling
      is unclear. Therefore, we analyzed the relationship between MBG levels derived
      from SMCG data and glucose data derived from continuous glucose monitoring (CGM).
      METHODS: SMCG and CGM were concurrently performed in 104 patients with diabetes
      and prediabetes over 3 to 6 days. MBG data obtained from SMCG and CGM were
      compared by standard correlation and Bland-Altman analyses. RESULTS: SMCG and CGM
      MBG data from the longest duration of sampling were highly correlated (r = 0.965;
      P<.001). Single-day MBG estimates from both sources were also highly correlated,
      with r values ranging from 0.833 to 0.927. A SMCG MBG level of 166.1 +/- 55 mg/dL
      (derived from 14.1 +/- 4.6 samples) tended to slightly underestimate the
      concurrent CGM MBG level of 171.1 +/- 56.4 mg/dL (derived from 1,063 +/- 283
      samples). The SMCG MBG was within 30 mg/dL of the CGM MBG in 94.6% of patients
      and within 15 mg/dL in 67% of patients. The difference between the estimates
      tended to increase with increasing SD of the MBG obtained from CGM (r = 0.38;
      P<.0001). CONCLUSION: MBG estimated from SMCG is a reasonable estimate of a
      patient's CGM MBG over the same period of time and with caveats could be used as
      a practical guide for long-term glycemic control that can be considered in tandem
      with the patient's hemoglobin A1c in endocrine practice.

PMID- 24449667
TI  - Thyroid physiology in pregnancy.
AB  - OBJECTIVE: Various physiological changes occur in maternal thyroid economy during
      pregnancy. This review focuses on the events taking place during gestation that
      together strongly influence maternal thyroid function. METHODS: Scientific
      reports on maternal thyroid physiology in pregnancy. RESULTS: During the 1st
      trimester, human chorionic gonadotropin (hCG) induces a transient increase in
      free thyroxine (FT4) levels, which is mirrored by a lowering of thyroid
      stimulating hormone (TSH) concentrations. Following this period, serum FT4
      concentrations decrease of approximately 10 to 15%, and serum TSH values steadily
      return to normal. Also starting in early gestation, there is a marked increase in
      serum thyroxine-binding globulin (TBG) concentrations, which peak around
      midgestation and are maintained thereafter. This event, in turn, is responsible
      for a significant rise in total T4 and triiodothyronine (T3). Finally,
      significant modifications in the peripheral metabolism of maternal thyroid
      hormones occur, due to the expression and activity of placental types 2 and 3
      iodothyronine deiodinases (D2 and D3, respectively). CONCLUSION: In line with
      these variations, both free thyroid hormone and TSH reference intervals change
      throughout pregnancy, and most scientific societies now recommend that method-
      and gestation-specific reference ranges be used for interpreting results in
      pregnancy.The maternal iodide pool reduces during pregnancy because of increased
      renal clearance of iodine and transfer of iodine to the feto-placental unit. This
      results in an additional requirement of iodine during pregnancy of ~100% as
      compared to nonpregnant adults. In accordance, the recommended iodine intake in
      pregnancy is 250 MUg/day. A daily iodine intake below this threshold poses risks
      of various degrees of thyroid insufficiency for both the mother and the fetus.

PMID- 24449668
TI  - Paradoxical Results after Inadvertent Use of Cosyntropin [Adrenocorticotropin
      Hormone (1-24)] Rather than Acthrel (Ovine Corticotropin Releasing Hormone)
      during Inferior Petrosal Sinus Sampling.
AB  - OBJECTIVE: The use of ovine corticotropin releasing hormone (oCRH) maximizes the
      diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with
      adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is
      marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH
      (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel)
      during IPSS may cause unexpected and misleading results. The aim of this report
      is to raise awareness of the potential confounding results created when synthetic
      ACTH(1-24) is mistakenly used during IPSS. METHODS: We present 3 patients treated
      at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly
      substituted for oCRH (ACTHrel) during IPSS. RESULTS: In all patients, there was
      an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus
      (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the
      patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used
      rather than oCRH during each procedure. Because "sandwich" immunometric assays
      for ACTH measure the entire pool of endogenous ACTH, the administration of
      synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39)
      measurement by binding only to the N-terminal antibody raised against ACTH(1-17)
      and not to the C-terminal antibody raised against ACTH(34-39). This results in a
      lack of a detectable sandwich complex and explains the apparent reduction in ACTH
      concentration. CONCLUSION: An abrupt decrease in ACTH during IPSS suggests that
      synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The
      labeling of oCRH as ACTHrel poses a potential patient safety problem about which
      endocrinologists, interventional radiologists, and pharmacists should be aware.

PMID- 24449669
TI  - Clinical aspects of hyperthyroidism, hypothyroidism, and thyroid screening in
      pregnancy.
AB  - OBJECTIVE: To evaluate the peer-reviewed literature on hypothyroidism,
      hyperthyroidism, and thyroid autoimmunity in pregnancy. METHODS: We review
      published studies on thyroid autoimmunity and dysfunction in pregnancy, the
      impact of thyroid disease on pregnancy, and discuss implications for screening.
      RESULTS: Overt hyperthyroidism and hypothyroidism are responsible for adverse
      obstetric and neonatal events. Several studies of association suggest that either
      subclinical hypothyroidism or thyroid autoimmunity increase the risk of
      complications. One randomized controlled trial showed that pregnant women with
      subclinical hypothyroidism benefit from treatment in terms of obstetric and
      neonatal complications, whereas another study demonstrated no benefit in the
      intelligence quotient of babies born to women with subclinical hypothyroidism.
      Thyroid autoimmunity has been associated with increased rate of pregnancy loss,
      recurrent miscarriage, and preterm delivery. CONCLUSION: Current guidelines agree
      that overt hyperthyroidism and hypothyroidism need to be promptly treated and
      that as potential benefits outweigh potential harm, subclinical hypothyroidism
      also requires substitutive treatment. The chance that women with thyroid
      autoimmunity may benefit from levothyroxine treatment to improve obstetric
      outcome is intriguing, but adequately powered randomized controlled trials are
      needed. The issue of universal thyroid screening at the beginning of pregnancy is
      still a matter of debate, and aggressive case-finding is supported.

PMID- 24449670
TI  - Pet imaging of the adrenal gland--utility and pitfalls.

PMID- 24449671
TI  - Healthcare transition from pediatric to adult medical homes in diabetes mellitus.
AB  - OBJECTIVE: To review and exemplify the complexities and challenges in healthcare
      transition from the pediatric medical home to the adult medical home for patients
      with type 1 and type 2 diabetes mellitus and to highlight the importance of this
      topic to adult-focused clinical endocrinologists. METHODS: We performed a
      literature search using PubMed and multiple key words. To set the scene for
      discussions, we also reviewed landmark publications in the general healthcare
      transition literature over the last several decades; we provide a brief
      historical perspective at the beginning of our discussions. RESULTS: Given the
      critical importance of successful healthcare transition, there is little
      empirical evidence on key aspects of these transitions. The vast majority of the
      literature focuses on type 1 diabetes because historically, this form has
      predominantly affected pediatric patients. However, the increasing incidence and
      prevalence of pediatric patients with type 2 diabetes makes investigations vital
      for this patient population too. The Treatment Options for Type 2 Diabetes in
      Adolescents and Youth study has proved informative in this regard. CONCLUSION:
      Crossing the chasm between pediatric and adult healthcare remains a remarkably
      flawed transition process. Healthcare transition should be a planned process of
      discussing and preparing pediatric patients for the transition and then ensuring
      continued care as an adult; the greater the collaboration of pediatric and adult
      endocrinologists in this process, the greater the chance of a successful
      transition.

PMID- 24449672
TI  - Healthcare costs and adherence associated with human regular U-500 versus high
      dose U-100 insulin in patients with diabetes.
AB  - OBJECTIVE: Describe the characteristics, costs, and adherence of patients
      receiving human regular U-500 insulin (U-500R) compared with those of patients
      receiving high-dose (>=150 units/day) U-100 insulin. METHODS: Data from Truven
      Health MarketScan Research Databases, July 1, 2008, through December 31, 2010,
      were used. The U-100 cohort received >=150 units/day of U-100 insulin for >=31
      days during the first 60 days after the index date. The U-500R cohort received
      >=2 prescriptions of U-500R after the index date. Analyses were performed on
      propensity-matched cohorts. The changes in annualized costs were compared between
      the 2 cohorts using paired t tests. Adherence was assessed by the proportion of
      days covered (PDC) and compared using a 2-sample t test. Glycemic efficacy data
      were not available in this database. RESULTS: There were 1,044 U-500R-treated
      patients (19.1% with type 1 diabetes [T1D]) and 11,520 U-100-treated patients
      (23.8% with T1D) identified, from which 1,039 matched pairs were obtained. The
      mean decrease of $1,290 in annual pharmacy costs for the U-500R cohort was
      significantly different from the mean increase of $2,586 for the U-100 cohort
      (P<.001; 95% confidence interval, -$4,345 to -$3,422). More U-500R patients
      experienced hypoglycemia (17.3% vs. 11.8%; P<.001), but the hypoglycemia rate per
      person and related costs were not significantly different between cohorts.
      Finally, the mean 12-month PDC was 65.0% for U-500R versus 47.6% for U-100
      patients (P<.0001). CONCLUSION: Compared with treatment with >=150 units/day of U
      100 insulin, treatment with U-500R was associated with decreases in pharmacy
      costs, a higher percentage of patients experiencing hypoglycemia, and greater
      treatment adherence.

PMID- 24449673
TI  - Pheochromocytoma and tetralogy of Fallot: a rare but potentially dangerous
      combination.
AB  - OBJECTIVE: To describe a case of pheochromocytoma (PHEO) with tetralogy of Fallot
      (TOF) and discuss the difficulties encountered during the management of this
      patient, with a review of the literature. METHODS: We report the clinical course,
      imaging, and management issues of our patient and review relevant literature.
      RESULTS: A 14-year-old female who was known to have TOF presented with classical
      paroxysmal symptoms and worsening dyspnea. She was diagnosed as having
      epinephrine-secreting PHEO based on biochemical, radiologic, and functional
      imaging. She was treated with an alpha-1 blocker for control of paroxysms but
      developed severe cyanotic spells. She required addition of a calcium-channel
      blocker for control of the paroxysms and underwent successful cardiac repair.
      CONCLUSION: Treatment of the combination of cyanotic congenital heart disease
      (CCHD) and PHEO requires an individualized and multidisciplinary approach with
      judicious use of available medications. This is the first case of uncorrected TOF
      and epinephrine-secreting PHEO. Our case also reiterates the need for further
      studies to better understand the pathophysiologic link between PHEO/paraganglioma
      and CCHD.

PMID- 24449674
TI  - Comparison of TSH Levels with Liquid Formulation Versus Tablet Formulations of
      Levothyroxine in the Treatment of Adult Hypothyroidism.
AB  - OBJECTIVE: A great number of factors can interfere with levothyroxine (LT4)
      tablet absorption, leading to increased serum thyroid-stimulating hormone (TSH)
      levels and, accordingly, to increased LT4 requirements. LT4 oral solution (LT4
      OS) is a novel formulation with a pharmacokinetics profile different from those
      of tablets. The aim of this study was to retrospectively evaluate whether serum
      TSH levels were decreased after switching adult hypothyroid patients from the
      tablet to LT-OS. METHODS: We retrospectively evaluated 53 outpatients on LT4
      replacement therapy (consumed within 1 hour before breakfast) who switched from
      LT4 tablets to LT4-OS without changing the daily dose. We compared preswitch TSH
      (TSH1) with TSH level 60 to 90 days after the switch (TSH2) and examined the
      clinical differences between the patients whose TSH did and did not drop after
      the switch. RESULTS: After the switch, TSH levels decreased from a median value
      of 3.04 (interquartile range [IQR] 1.75-6.80) to 2.30 (IQR 1.21-3.81) MUIU/mL,
      and the difference was significant (P = .0034). We observed a TSH reduction
      (TSH2/TSH1 ratio <1) in 36/53 (67.9%) of patients; the median TSH2/TSH1 ratio was
      0.71 (IQR 0.37-1.14). In the group of patients whose TSH dropped, we observed an
      increased frequency of factors interfering with LT4 absorption (P = .014). The
      median TSH2/TSH1 ratios were 0.50 (IQR 0.31-0.72) and 0.85 (IQR 0.65-1.36) for
      patients with and without interfering factors, respectively. CONCLUSION: Our
      study confirms that LT4-OS could have an increased absorption rate in comparison
      to LT4 tablets, especially in the presence of other factors interfering with LT4
      absorption.

PMID- 24449675
TI  - The association between body mass index and increased utilization of healthcare
      services: a retrospective cohort study of 51,521 young adult males.
AB  - OBJECTIVE: To examine the association between the entire body mass index (BMI)
      range and healthcare utilization. METHODS: Weight and height were measured during
      medical examinations of recruits prior to their entry into the military in
      Israel. All recruits were followed-up during service and all of their medical
      information was recorded in a central electronic medical record. We extracted
      medical and sociodemographic data for all Jewish male combat recruits during
      their first year of service. The study included 51,521 subjects who were divided
      into quintiles according to BMI. Using logistic regression models, we determined
      the association between BMI and high numbers of physician encounters, emergency
      room visits, referrals to specialists, imaging, laboratory tests, and medication
      prescriptions. RESULTS: In comparison with the lowest BMI quintile, there was a
      significant increase in the highest quintile with regard to an increased number
      of physician encounters (odds ratio [OR], 1.27; 95% confidence interval [CI],
      1.19-1.36), emergency room visits (OR, 1.2; 95% CI, 1.12-1.29), referrals to
      specialists (OR, 1.22; 95% CI, 1.14-1.31), and medication prescriptions (OR,
      1.23; 95% CI, 1.15-1.32). An increase in the number of laboratory tests was not
      statistically significant and there was no difference in imaging referrals.
      Adjustment for various sociodemographic variables and medical conditions did not
      significantly change the results. CONCLUSION: Higher BMI is related to increased
      utilization of healthcare services, even for BMI values in the normal range.

PMID- 24449676
TI  - A patient with an apparently sporadic pheochromocytoma with a rearranged during
      transfection codon 635 variant: a mild form of multiple endocrine neoplasia type
      2?
AB  - OBJECTIVE: Multiple endocrine neoplasia 2 (MEN2) is an autosomal dominant
      disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma,
      and hyperparathyroidism, with mutations at codon 634 in exon 11 of the RET
      (REarranged during Transfection) proto-oncogene identified as the most common
      genetic defect. METHODS: We present a patient diagnosed with a left adrenal
      pheochromocytoma at a young age in whom we identified a mutation at codon 635 of
      the RET gene. No MTC has been clinically detected during a 6-year follow-up.
      RESULTS: The C-to-T point mutation at nucleotide c.1903 results in an additional
      cysteine in the cysteine-rich domain due to the replacement of arginine with
      cysteine. One of the patient's 2 children has the same sequence variant in the
      RET proto-oncogene and has remained unaffected during follow-up. CONCLUSIONS: The
      majority of mutations in this disorder affect cysteine residues in the cysteine
      rich region of the extracellular domain of the RET protein, disrupting normal
      cysteine pairing. Consequently, we consider that this variant is likely of
      pathogenic significance, but this has not been unequivocally confirmed.

PMID- 24449677
TI  - Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta
      analysis.
AB  - OBJECTIVE: The association between subclinical hypothyroidism (SCH) and
      gestational diabetes mellitus (GDM) is controversial. This review evaluates
      whether the risk of GDM is different in pregnant women with SCH compared to
      euthyroid pregnant women. METHODS: A computerized search of the MEDLINE and
      EMBASE databases was conducted from their inceptions to July 2013 and was
      complemented with the perusal of the reference sections of the retrieved
      articles. Prespecified criteria were applied to assess eligibility, and standard
      meta-analytic methodology was employed for evidence synthesis. RESULTS: Six
      cohort studies, reporting data on 35,350 pregnant women (1,216 women with SCH),
      were identified. The risk of GDM in pregnant women with SCH was found to be
      substantially higher compared to euthyroid pregnant women (5 studies, pooled
      unadjusted odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.05-1.75, I2:
      41%, Harbord test P = .44). Similarly, the risk of GDM was estimated to be
      significantly higher in pregnant women with SCH when using adjusted estimates (3
      studies, pooled adjusted OR: 1.39, 95% CI: 1.07-1.79, I2: 0%). Neither finding
      remained significant in sensitivity analyses. CONCLUSION: A modestly increased
      risk of GDM might be present in pregnant women with SCH compared to euthyroid
      pregnant women. Assuming a 5% baseline risk of GDM and that SCH increases the
      risk of GDM by 50% (in odds) compared to a euthyroid population, then there would
      be 1 extra case of GDM in every 43 pregnant women with SCH. This preliminary
      finding warrants further investigation.

PMID- 24449678
TI  - Usefulness of two-stage ethanol ablation in the treatment of benign predominantly
      cystic thyroid nodules.
AB  - OBJECTIVE: The management of benign predominantly cystic thyroid nodules (PCTNs)
      differs depending on the institution or practitioner. This study aimed to assess
      the efficacy of two-stage ultrasound (US)-guided ethanol ablation (EA) in
      treating PCTNs. METHODS: Over a 1-year period, two-stage EA was performed on
      benign PCTNs for 25 patients. After EA, each patient was followed up with thyroid
      US. The two-stage EA treatment consisted of an initial EA for the cystic
      component of the PCTN and subsequent treatment for the remaining solid component,
      if needed. RESULTS: All 25 patients underwent EA for the cystic component of a
      PCTN and showed complete collapse of the cystic component on the follow-up US.
      Twenty patients were subsequently treated with one or more EA sessions because of
      the presence of a vascularized solid component, whereas 5 patients underwent no
      additional EA sessions because no vascularized solid component was detected on
      follow-up US. Of the 20 patients who underwent additional EA for a remaining
      solid component, complete ablation (n = 9), incomplete ablation (n = 7), and no
      response (n = 4) were observed on follow-up US. Of the 7 patients with incomplete
      ablation despite repeated EA, only 4 underwent radiofrequency ablation, and they
      showed complete ablation on follow-up US. CONCLUSION: Two-stage EA may be useful
      for the treatment of benign PCTNs.

PMID- 24449679
TI  - Novel BRAFI599Ins Mutation Identified in a Follicular Variant of a Papillary
      Thyroid Carcinoma: A Molecular Modeling Approach.
AB  - OBJECTIVE: BRAF mutations are the most common genetic alteration found in
      papillary thyroid carcinoma (PTC). Approximately, 90% correspond to BRAFV600E,
      although other less common BRAF mutations have been described. The aim of this
      study was to describe a new mutation on BRAF gene discovered on the previous
      thyroid cytology of a patient diagnosed with a follicular variant of PTC (FV
      PTC). METHODS: The mutation was identified by independent cloning of the 2
      alleles and direct sequencing in the previous cytology and tumor tissue samples
      from a patient diagnosed with FV-PTC. To elucidate the effect of the mutation on
      the structure and hence on the activating mechanism of the protein, the
      structures of BRAFI599Ins, BRAFT599Ins, BRAFV599Ins and BRAFV600E were modeled by
      using the reconstructed wild-type BRAF (BRAFWT) crystal structure. RESULTS: The
      novel mutation in BRAF consisted in the in-frame insertion of 3 nucleotides (TAA)
      after nucleotide 1795, resulting in the incorporation of an extra isoleucine
      residue at position 599 (BRAFI599Ins) of the protein. The structural comparison
      of BRAFI599Ins, BRAFT599Ins, BRAFV599Ins with BRAFWT, and BRAFV600E models
      revealed that the overall shape of the kinase was conserved in the protein
      produced by this novel mutation, except for the displacement of the activation
      loop (A-loop), as a direct consequence of the increase in loop size, and the
      exposition of 1 of the 2 residues involved in BRAF activation (T599), probably
      facilitating its phosphorylation. CONCLUSION: BRAFI599Ins mutation constitutes a
      new BRAF mutation affecting the length of the A-loop, which most likely
      facilitates BRAF activation by altering the A-loop conformation.

PMID- 24449680
TI  - Comparison of the expectations of caregivers and children with type 1 diabetes
      mellitus for independence in diabetes care-related tasks.
AB  - OBJECTIVE: Children who are given unsupervised responsibility for their diabetes
      care prior to developmental and/or emotional readiness may have poorer glycemic
      control. The purpose of this study was to assess the age-related expectations of
      children and caregivers for independence in diabetes care-related tasks. METHODS:
      A total of 150 participants with type 1 diabetes mellitus (T1DM) receiving
      multiple daily injections (MDI) or continuous subcutaneous insulin infusion
      (CSII) were enrolled in this study. All caregivers and participants older than 10
      years of age completed questionnaires evaluating the expected age of independence
      for different diabetes care-related tasks. RESULTS: The participants expected
      independence with no direct supervision in most diabetes care-related tasks at a
      younger age than their caregivers (P<.05). The difference was more prominent for
      those on CSII compared to MDI (P<.01). There was a positive correlation between
      the age when caregivers expect independence for most of the diabetes-related
      tasks and the age at diagnosis, regardless of the use of MDI or CSII (P<.01).
      CONCLUSION: Children with T1DM expect to assume independence at a younger age
      than their caregivers do. The younger the children are at diagnosis, the younger
      they are expected by their caregivers to be independent, especially those on
      CSII.

PMID- 24449681
TI  - Visual vignette.

PMID- 24449683
TI  - Conformationally restricted aza-dipyrromethene boron difluorides (aza-BODIPYs)
      with high fluorescent quantum yields.
AB  - A simple approach to the highly fluorescent near-infrared aza-BODIPY dyes with
      higher fluorescence quantum yields (up to 0.81 in toluene) in comparison with
      their known analogues is presented. Our approach is based on the restricted
      rotations of the 1,7-phenyl groups to the mean plane of the aza-BODIPYs, which is
      achieved through the installation of bulky substituents on the 1,7-phenyl groups
      of aza-BODIPYs and results in a reduced nonradiative relaxation process in
      solution. The large torsion angles between the 1,7-phenyl groups and the aza
      BODIPY core (phi1 and phi2 in these novel conformationally restricted aza
      BODIPYs) were confirmed by X-ray diffraction studies. 

PMID- 24449682
TI  - The safety and efficacy of short-term budesonide delivered via mucosal
      atomization device for chronic rhinosinusitis without nasal polyposis.
AB  - BACKGROUND: Budesonide is a potent corticosteroid commonly prescribed for
      management of inflammation in chronic rhinosinusitis (CRS). The standard for
      prescribing budesonide is via impregnated nasal saline irrigation (INSI),
      although recently the mucosal atomization device (MAD) has emerged as a
      theoretically superior method of distributing medication into the sinuses. The
      MAD atomizes medication into small droplets and this is thought to enhance
      absorption and improve bioavailability. However, no studies have shown whether
      enhanced absorption and improved bioavailability of budesonide via MAD causes
      adrenal suppression. The objective of this study is to determine whether
      budesonide via MAD affects the hypothalamic-pituitary-adrenal (HPA) axis.
      METHODS: Twenty CRS patients were recruited from a tertiary rhinology clinic and
      randomized to take budesonide (1 mg) via MAD or via INSI twice a day for 60 days.
      The adrenocorticotropic hormone (ACTH) stimulation test and 22-item Sinonasal
      Outcomes Test (SNOT-22) questionnaire were administered on days 1, 30, and 60 of
      the study. Plasma budesonide and cortisol levels were simultaneously quantified
      using a high-performance liquid chromatography-tandem mass spectrometry
      technique. RESULTS: There was no indication of adrenal suppression in either
      group (n = 20) based on ACTH stimulation test results nor was there significant
      plasma budesonide levels detected in either group. Quality of life, as indicated
      by SNOT-22, did not differ between groups at 60 days (p = 0.404; 95% confidence
      interval [CI], -37.2 to 15.9), but SNOT-22 scores for patients using MAD did show
      statistically significant improvement at 60 days compared to baseline (p = 0.02).
      CONCLUSION: The MAD is likely a safe and effective method of delivering
      budesonide to the sinuses in the short term.

PMID- 24449684
TI  - Toward cell-free biofuel production: Stable immobilization of oligomeric enzymes.
AB  - To overcome the main challenges facing alcohol-based biofuel production, we
      propose an alternate simplified biofuel production scheme based on a cell-free
      immobilized enzyme system. In this paper, we measured the activity of two
      tetrameric enzymes, a control enzyme with a colorimetric assay, beta
      galactosidase, and an alcohol-producing enzyme, alcohol dehydrogenase,
      immobilized on multiple surface curvatures and chemistries. Several solid
      supports including silica nanoparticles (convex), mesopourous silica (concave),
      diatomaceous earth (concave), and methacrylate (concave) were examined. High
      conversion rates and low protein leaching was achieved by covalent immobilization
      of both enzymes on methacrylate resin. Alcohol dehydrogenase (ADH) exhibited long
      term stability and over 80% conversion of aldehyde to alcohol over 16 days of
      batch cycles. The complete reaction scheme for the conversion of acid to aldehyde
      to alcohol was demonstrated in vitro by immobilizing ADH with keto-acid
      decarboxylase free in solution.

PMID- 24449685
TI  - Early enteral nutrition in critically ill patients with hemodynamic instability:
      an evidence-based review and practical advice.
AB  - Early enteral nutrition (EEN) in critically ill patients is associated with
      significant benefit as well as elevated risk of complications. Concomitant use of
      EEN with vasopressors has been associated with nonocclusive bowel necrosis in
      critically ill patients with hemodynamic instability. The decision when to
      initiate enteral nutrition in hemodynamically unstable patients that require
      vasoactive substances remains a clinical dilemma. This review summarizes the
      effect of EEN and vasoactive agents on gastrointestinal blood flow and perfusion
      in critically ill patients, based on current evidence. Animal and clinical data
      involving simultaneous administration of EEN and vasoactive agents for
      hemodynamic instability are reviewed, and the factors related to the safety and
      effectiveness of EEN support in this patient population are analyzed. Moreover,
      practical recommendations are provided. Additional randomized clinical trials are
      warranted to provide cutting-edge evidence-based guidance about this issue for
      practitioners of critical care. 

PMID- 24449686
TI  - Reduced rDNA copy number does not affect "competitive" chromosome pairing in XYY
      males of Drosophila melanogaster.
AB  - The ribosomal DNA (rDNA) arrays are causal agents in X-Y chromosome pairing in
      meiosis I of Drosophila males. Despite broad variation in X-linked and Y-linked
      rDNA copy number, polymorphisms in regulatory/spacer sequences between rRNA
      genes, and variance in copy number of interrupting R1 and R2 retrotransposable
      elements, there is little evidence that different rDNA arrays affect pairing
      efficacy. I investigated whether induced rDNA copy number polymorphisms affect
      chromosome pairing in a "competitive" situation in which complex pairing
      configurations were possible using males with XYY constitution. Using a common
      normal X chromosome, one of two different full-length Y chromosomes, and a third
      chromosome from a series of otherwise-isogenic rDNA deletions, I detected no
      differences in X-Y or Y-Y pairing or chromosome segregation frequencies that
      could not be attributed to random variation alone. This work was performed in the
      context of an undergraduate teaching program at Texas A&M University, and I
      discuss the pedagogical utility of this and other such experiments. 

PMID- 24449687
TI  - Heteroscedastic ridge regression approaches for genome-wide prediction with a
      focus on computational efficiency and accurate effect estimation.
AB  - Ridge regression with heteroscedastic marker variances provides an alternative to
      Bayesian genome-wide prediction methods. Our objectives were to suggest new
      methods to determine marker-specific shrinkage factors for heteroscedastic ridge
      regression and to investigate their properties with respect to computational
      efficiency and accuracy of estimated effects. We analyzed published data sets of
      maize, wheat, and sugar beet as well as simulated data with the new methods.
      Ridge regression with shrinkage factors that were proportional to single-marker
      analysis of variance estimates of variance components (i.e., RRWA) was the
      fastest method. It required computation times of less than 1 sec for medium-sized
      data sets, which have dimensions that are common in plant breeding. A
      modification of the expectation-maximization algorithm that yields
      heteroscedastic marker variances (i.e., RMLV) resulted in the most accurate
      marker effect estimates. It outperformed the homoscedastic ridge regression
      approach for best linear unbiased prediction in particular for situations with
      high marker density and strong linkage disequilibrium along the chromosomes, a
      situation that occurs often in plant breeding populations. We conclude that the
      RRWA and RMLV approaches provide alternatives to the commonly used Bayesian
      methods, in particular for applications in which computational feasibility or
      accuracy of effect estimates are important, such as detection or functional
      analysis of genes or planning crosses. 

PMID- 24449689
TI  - An E4 ligase facilitates polyubiquitination of plant immune receptor resistance
      proteins in Arabidopsis.
AB  - Proteins with nucleotide binding and leucine-rich repeat domains (NLRs) serve as
      immune receptors in animals and plants that recognize pathogens and activate
      downstream defense responses. As high accumulation of NLRs can result in
      unwarranted autoimmune responses, their cellular concentrations must be tightly
      regulated. However, the molecular mechanisms of this process are poorly detailed.
      The F-box protein Constitutive expressor of PR genes 1 (CPR1) was previously
      identified as a component of a Skp1, Cullin1, F-box protein E3 complex that
      targets NLRs, including Suppressor of NPR1, Constitutive 1 (SNC1) and Resistance
      to Pseudomonas syringae 2 (RPS2), for ubiquitination and further protein
      degradation. From a forward genetic screen, we identified Mutant, snc1-enhancing
      3 (MUSE3), an E4 ubiquitin ligase involved in polyubiquitination of its protein
      targets. Knocking out MUSE3 in Arabidopsis thaliana results in increased levels
      of NLRs, including SNC1 and RPS2, whereas overexpressing MUSE3 together with CPR1
      enhances polyubiquitination and protein degradation of these immune receptors.
      This report on the functional role of an E4 ligase in plants provides insight
      into the scarcely understood NLR degradation pathway.

PMID- 24449688
TI  - Thylakoid FtsH protease contributes to photosystem II and cytochrome b6f
      remodeling in Chlamydomonas reinhardtii under stress conditions.
AB  - FtsH is the major thylakoid membrane protease found in organisms performing
      oxygenic photosynthesis. Here, we show that FtsH from Chlamydomonas reinhardtii
      forms heterooligomers comprising two subunits, FtsH1 and FtsH2. We characterized
      this protease using FtsH mutants that we identified through a genetic suppressor
      approach that restored phototrophic growth of mutants originally defective for
      cytochrome b6f accumulation. We thus extended the spectrum of FtsH substrates in
      the thylakoid membranes beyond photosystem II, showing the susceptibility of
      cytochrome b6f complexes (and proteins involved in the ci heme binding pathway to
      cytochrome b6) to FtsH. We then show how FtsH is involved in the response of C.
      reinhardtii to macronutrient stress. Upon phosphorus starvation, photosynthesis
      inactivation results from an FtsH-sensitive photoinhibition process. In contrast,
      we identified an FtsH-dependent loss of photosystem II and cytochrome b6f
      complexes in darkness upon sulfur deprivation. The D1 fragmentation pattern
      observed in the latter condition was similar to that observed in photoinhibitory
      conditions, which points to a similar degradation pathway in these two widely
      different environmental conditions. Our experiments thus provide extensive
      evidence that FtsH plays a major role in the quality control of thylakoid
      membrane proteins and in the response of C. reinhardtii to light and
      macronutrient stress. 

PMID- 24449690
TI  - A linearly convergent first-order algorithm for total variation minimisation in
      image processing.
AB  - We introduce a new formulation for total variation minimisation in image
      denoising. We also present a linearly convergent first-order method for solving
      this reformulated problem and show that it possesses a nearly dimension
      independent iteration complexity bound. 

PMID- 24449691
TI  - Uses and challenges of bioinformatic tools in mass spectrometric-based proteomic
      brain perturbation studies.
AB  - Mass spectrometry (MS) has become the method of choice to study the proteome of
      brain injury. The high throughput nature of MS-based proteomic experiments
      generates massive amount of mass spectral data presenting great challenges in
      downstream interpretation. Currently, different bioinformatics platforms are
      available for functional analysis and data mining of MS-generated proteomic data.
      These tools provide a way to convert data sets to biologically interpretable
      results and functional outcomes. In this review, a brief overview of the
      currently available bioinformatics strategies applied to neuroproteomic studies
      is presented. Application of commercially available bioinformatics software to
      different brain injury studies demonstrates integration of the data mining and
      analysis applications into neuroproteomic workflows that can identify major
      protein markers as well as highlight the biological processes and molecular
      functions involved. 

PMID- 24449692
TI  - Learning dependence from samples.
AB  - Mutual information, conditional mutual information and interaction information
      have been widely used in scientific literature as measures of dependence,
      conditional dependence and mutual dependence. However, these concepts suffer from
      several computational issues; they are difficult to estimate in continuous
      domain, the existing regularised estimators are almost always defined only for
      real or vector-valued random variables, and these measures address what
      dependence, conditional dependence and mutual dependence imply in terms of the
      random variables but not finite realisations. In this paper, we address the issue
      that given a set of realisations in an arbitrary metric space, what
      characteristic makes them dependent, conditionally dependent or mutually
      dependent. With this novel understanding, we develop new estimators of
      association, conditional association and interaction association. Some attractive
      properties of these estimators are that they do not require choosing free
      parameter(s), they are computationally simpler, and they can be applied to
      arbitrary metric spaces. 

PMID- 24449693
TI  - Space pruning monotonic search for the non-unique probe selection problem.
AB  - Identification of targets, generally viruses or bacteria, in a biological sample
      is a relevant problem in medicine. Biologists can use hybridisation experiments
      to determine whether a specific DNA fragment, that represents the virus, is
      presented in a DNA solution. A probe is a segment of DNA or RNA, labelled with a
      radioactive isotope, dye or enzyme, used to find a specific target sequence on a
      DNA molecule by hybridisation. Selecting unique probes through hybridisation
      experiments is a difficult task, especially when targets have a high degree of
      similarity, for instance in a case of closely related viruses. After preliminary
      experiments, performed by a canonical Monte Carlo method with Heuristic Reduction
      (MCHR), a new combinatorial optimisation approach, the Space Pruning Monotonic
      Search (SPMS) method, is introduced. The experiments show that SPMS provides high
      quality solutions and outperforms the current state-of-the-art algorithms. 

PMID- 24449694
TI  - Perpendicular fibre tracking for neural fibre bundle analysis using diffusion
      MRI.
AB  - Information on the directionality and structure of axonal fibres in neural tissue
      can be obtained by analysing diffusion-weighted MRI data sets. Several fibre
      tracking algorithms have been presented in the literature that trace the
      underlying field of principal orientations of water diffusion, which correspond
      to the local primary eigenvectors of the diffusion tensor field. However, the
      majority of the existing techniques ignore the secondary and tertiary
      orientations of diffusion, which contain significant information on the local
      patterns of diffusion. In this paper, we introduce the idea of perpendicular
      fibre tracking and present a novel dynamic programming method that traces
      surfaces, which are locally perpendicular to the axonal fibres. This is achieved
      by using a cost function, with geometric and fibre orientation constraints, that
      is evaluated dynamically for every voxel in the image domain starting from a
      given seed point. The proposed method is tested using synthetic and real DW-MRI
      data sets. The results conclusively demonstrate the accuracy and effectiveness of
      our method. 

PMID- 24449695
TI  - Integrating edge detection and fuzzy connectedness for automated segmentation of
      anatomical branching structures.
AB  - Image segmentation algorithms are critical components of medical image analysis
      systems. This paper presents a novel and fully automated methodology for
      segmenting anatomical branching structures in medical images. It is a hybrid
      approach which integrates the Canny edge detection to obtain a preliminary
      boundary of the structure and the fuzzy connectedness algorithm to handle
      efficiently the discontinuities of the returned edge map. To ensure efficient
      localisation of weak branches, the fuzzy connectedness framework is applied in a
      sliding window mode and using a voting scheme the optimal connection point is
      estimated. Finally, the image regions are labelled as tissue or background using
      a locally adaptive thresholding technique. The proposed methodology is applied
      and evaluated in segmenting ductal trees visualised in clinical X-ray
      galactograms and vasculature visualised in angiograms. The experimental results
      demonstrate the effectiveness of the proposed approach achieving high scores of
      detection rate and accuracy among state-of-the-art segmentation techniques. 

PMID- 24449696
TI  - Vectorial total variation regularisation of orientation distribution functions in
      diffusion weighted MRI.
AB  - We propose a model for simultaneous Orientation Distribution Function (ODF)
      reconstruction and regularisation. The ODFs are represented by real spherical
      harmonic functions, and we propose to solve the spherical harmonic coefficients
      of the ODFs, with spatial regularisation by minimising the Vectorial Total
      Variation (VTV) of the coefficients. The proposed model also incorporates angular
      regularisation of the ODFs using Laplace-Beltrami operator on the unit sphere. A
      modified primal-dual hybrid gradient algorithm is applied to solve the model
      efficiently. The experimental results indicate better directional structures of
      reconstructed ODFs. 

PMID- 24449697
TI  - Defining quality metrics and improving safety and outcome in allergy care.
AB  - BACKGROUND: The delivery of allergy immunotherapy in the otolaryngology office is
      variable and lacks standardization. Quality metrics encompasses the measurement
      of factors associated with good patient-centered care. These factors have yet to
      be defined in the delivery of allergy immunotherapy. We developed and applied
      quality metrics to 6 allergy practices affiliated with an academic otolaryngic
      allergy center. METHODS: This work was conducted at a tertiary academic center
      providing care to over 1500 patients. We evaluated methods and variability
      between 6 sites. Tracking of errors and anaphylaxis was initiated across all
      sites. A nationwide survey of academic and private allergists was used to collect
      data on current practice and use of quality metrics. RESULTS: The most common
      types of errors recorded were patient identification errors (n = 4), followed by
      vial mixing errors (n = 3), and dosing errors (n = 2). There were 7 episodes of
      anaphylaxis of which 2 were secondary to dosing errors for a rate of 0.01% or 1
      in every 10,000 injection visits/year. Site visits showed that 86% of key safety
      measures were followed. Analysis of nationwide survey responses revealed that
      quality metrics are still not well defined by either medical or otolaryngic
      allergy practices. Academic practices were statistically more likely to use
      quality metrics (p = 0.021) and perform systems reviews and audits in comparison
      to private practices (p = 0.005). CONCLUSION: Quality metrics in allergy delivery
      can help improve safety and quality care. These metrics need to be further
      defined by otolaryngic allergists in the changing health care environment.

PMID- 24449698
TI  - An efficient probe for rapid detection of cyanide in water at parts per billion
      levels and naked-eye detection of endogenous cyanide.
AB  - A new molecular probe based on an oxidized bis-indolyl skeleton has been
      developed for rapid and sensitive visual detection of cyanide ions in water and
      also for the detection of endogenously bound cyanide. The probe allows the "naked
      eye" detection of cyanide ions in water with a visual color change from red to
      yellow (Deltalambdamax =80 nm) with the immediate addition of the probe. It shows
      high selectivity towards the cyanide ion without any interference from other
      anions. The detection of cyanide by the probe is ratiometric, thus making the
      detection quantitative. A Michael-type addition reaction of the probe with the
      cyanide ion takes place during this chemodosimetric process. In water, the
      detection limit was found to be at the parts per million level, which improved
      drastically when a neutral micellar medium was employed, and it showed a parts
      per-billion-level detection, which is even 25-fold lower than the permitted
      limits of cyanide in water. The probe could also efficiently detect the
      endogenously bound cyanide in cassava (a staple food) with a clear visual color
      change without requiring any sample pretreatment and/or any special reaction
      conditions such as pH or temperature. Thus the probe could serve as a practical
      naked-eye probe for "in-field" experiments without requiring any sophisticated
      instruments. 

PMID- 24449700
TI  - A comparison of ethical issues in nursing practice across nursing units.
AB  - BACKGROUND: The complexity and variety of ethical issues in nursing is always
      increasing, and those issues lead to special concerns for nurses because they
      have critical impacts on nursing practice. RESEARCH OBJECTIVES: The purpose of
      this study was to gather comprehensive information about ethical issues in
      nursing practice, comparing the issues in different types of nursing units
      including general units, oncology units, intensive care units, operating rooms,
      and outpatient departments. RESEARCH DESIGN: The study used a descriptive
      research design. Ethics/human rights issues encountered by nurses in their daily
      nursing practice were identified by using the Ethical Issues Scale. PARTICIPANTS:
      The study sample included 993 staff nurses working in a university hospital in
      South Korea. ETHICAL CONSIDERATIONS: This study was approved by the University
      Institutional Review Board. Completed questionnaires were returned sealed with
      signed informed consent. FINDINGS: The most frequently and disturbingly
      encountered issues across nursing units were "conflicts in the nurse-physician
      relationship," "providing care with a possible risk to your health," and
      "staffing patterns that limit patient access to nursing care." The findings of
      this study showed that nurses from different nursing units experienced
      differences in the types or frequency of ethical issues. In particular, intensive
      care units had the greatest means of all the units in all three component scales
      including end-of-life treatment issues, patient care issues, and human rights
      issues. DISCUSSION: Nurses experienced various ethical challenges in their daily
      practice. Of the ethical issues, some were distinctively and frequently
      experienced by nurses in a specific unit. CONCLUSION: This study suggested that
      identifying and understanding specific ethical issues faced by nurses in their
      own areas may be an effective educational approach to motivate nurses and to
      facilitate nurses' reflection on their experiences.

PMID- 24449701
TI  - The search for little SMEs.

PMID- 24449699
TI  - Forward and reverse mutagenesis in C. elegans.
AB  - Mutagenesis drives natural selection. In the lab, mutations allow gene function
      to be deciphered. C. elegans is highly amendable to functional genetics because
      of its short generation time, ease of use, and wealth of available gene
      alteration techniques. Here we provide an overview of historical and contemporary
      methods for mutagenesis in C. elegans, and discuss principles and strategies for
      forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific
      mutagenesis) genetic studies in this animal. 

PMID- 24449702
TI  - Military surgery in the new curriculum: whither general surgery training in
      uniform?
AB  - BACKGROUND: The nature of general surgical training within the UK has undergone
      significant changes recently, including the evolution of the Intercollegiate
      Surgical Curriculum Programme (ISCP). In 2013, new task-specific goals tailored
      towards military surgery were incorporated into the general surgery curriculum.
      In order to meet the demands of training the next generation of military general
      surgeons, a new compendium of workplace-based assessments (WBAs) is now required.
      ADDRESSING THE NEED: In 2013, the ISCP general surgery curriculum was revised to
      include new, military-specific WBAs to allow formative assessment of a trainees'
      experience and preparedness for their future deployed role. Index procedures
      considered mandatory for a deployed military general surgeon to be effective in
      the field are now included in the general surgery curriculum. These will permit
      formative assessment of trainees and also permit revalidation of deployed skills
      among the consultant cadre. CONCLUSIONS: General surgical training in the UK is
      in a transitional period, and the move towards increased sub-specialisation
      appears inexorable as evidenced by the split of Vascular Surgery into a separate
      specialty, along with its own training pathway and curriculum. With the
      'generalist' demands on deployed surgeons in the Defence Medical Services, the
      task of training towards broader surgical competencies may appear daunting.
      Inclusion of defined military WBAs into the curriculum should help focus trainees
      and their trainers to identify the deployed general surgical skill set, identify
      the appropriate learning opportunities/placements required to enable the
      acquisition of relevant competencies and document their attainment and later
      retention.

PMID- 24449703
TI  - A system for the management, display and integration of pre-hospital healthcare
      activity in the deployed environment.
AB  - AIM: To create and implement a system through which pre-hospital healthcare
      activity across an entire operational theatre could be made available in real
      time to support healthcare delivery, governance and assurance activity. METHODS:
      An IT-based system was created that could display, manage and integrate the pre
      hospital healthcare activity on Op HERRICK 18. The system was based on the
      Defence Medical Services Common Assurance Framework and run through Microsoft
      Office SharePoint. RESULTS: Pre-hospital healthcare activity was made available
      and visible across an operational theatre. This supported delivery, assurance and
      governance at any time. Activity from each medical facility could be integrated
      and display automatically improving theatre wide situational awareness. The
      availability of information resulted in a shift towards a more continuous process
      of assurance and governance rather than reliance on inherently threatening and
      increasingly intermittent inspection regimes. DISCUSSION: The ability to review
      healthcare activity remotely at anytime significantly improves the validity of
      assurance possible for a deployed force. Governance activity can be more
      responsive and less reliant on the fixed timescale and datasets of reports from
      outlying medical facilities. However, assurance and governance authorities must
      not allow such a wealth of information to impact local leadership and innovation
      through a perception of, or actual, micro-management.

PMID- 24449704
TI  - Physiology studies at high altitude; why and how.
AB  - The military has always had an important role in high altitude research. This is
      due to the fact that mountainous regions often span borders and provide a safe
      haven to enemies. Deploying troops rapidly into high altitude environments
      presents major problems in terms of the development of high altitude illness.
      This paper examines the rationale for carrying out research at high altitude and
      the opportunities within the UK Defence Medical Services for carrying out this
      research. 

PMID- 24449705
TI  - Assessment of stress associated with an oral public speech in veterinary students
      by salivary biomarkers.
AB  - In this report, salivary cortisol, alpha-amylase activity, and testosterone were
      measured to assess stress associated with a public oral presentation in
      Veterinary Clinical Pathology students. Stimulated saliva samples were collected
      before and directly after a 5-minute oral presentation and at 20 and 35 minutes
      after the beginning of the presentation. Cortisol peaked 20 minutes after the
      beginning of the presentation, whereas salivary alpha-amylase (sAA) peaked at 5
      minutes, just at the end of the speech. These changes were not related to the
      level of stress that was indicated by the student in a questionnaire, the
      student's sex, or the quality of the presentation. No changes were detected in
      testosterone levels during the study. Saliva biomarkers evaluated in this
      research could be extended to other stress-producing situations in the university
      life of veterinary students. 

PMID- 24449706
TI  - Strengthening health promotion in hospitals with capacity building: a Taiwanese
      case study.
AB  - Organizational capacity building for health promotion (HP) is beneficial to the
      effective implementation of HP in organizational settings. The World Health
      Organization (WHO) Health Promoting Hospitals' (HPHs) initiative encourages
      hospitals to promote the health of their stakeholders by developing
      organizational capacity. This study analyzes an application case of one hospital
      of the HPH initiative in Taiwan, characterizes actions aiming at building
      organizational support to strengthen health gains and identifies facilitators of
      and barriers to the implementation of the HP in this hospital. Case study
      methodology was used with a triangulation of various sources; thematic analysis
      was used to analyze qualitative information. This study found a positive impact
      of the HPH initiative on the case hospital, such as more support from leadership,
      a fine-tuned HP mission and strategy, cultivated pro-HP habits of physical
      activities, a supportive intramural structure, an HP-inclusive system, improved
      management practices and enhanced staff participation. Transformational and
      transactional enablers are of equal importance in implementing HPH. However, it
      was also found that the case hospital encountered more transactional barriers
      than transformational ones. This hospital was hindered by insufficient support
      from external environments, leadership with limited autonomy and authority, a
      preference for ideals over professionalism, insufficient participation by
      physicians, a lack of manpower and time, a merit system with limited stimulating
      effect, ineffective management practices in weak central project management, a
      lack of integration, insufficient communication and an inability to inculcate the
      staff on the importance of HP, and inadequate staff participation. Several
      implications for other hospitals are suggested. 

PMID- 24449707
TI  - Luba-Kasai Men and the Prevention of Mother to Child Transmission (PMTCT) of HIV
      program in Lusaka.
AB  - Male participation in the prevention of mother-to-child transmission (PMTCT) of
      HIV has been determined as one of the key factors in sub-Saharan African
      countries, but its realization is challenging because of male-related and
      institutional factors. The purpose of this study is two-fold: first, we explored
      the views of Luba-Kasai men, living in Zambia in the Lusaka Province, on the
      factors that encourage, inconvenience or inhibit them in accompanying their wives
      to the antenatal clinic and their ideas to improve their experience. Secondly,
      the study considered their knowledge of the PMTCT program and how such knowledge
      conformed to the Zambian National Protocol Guidelines Integrated PMTCT of HIV /:
      AIDS. Twenty-one interviews were analyzed using qualitative inductive content
      analysis. The National Protocol Guidelines Integrated PMTCT of HIV/AIDS were
      analyzed using the deductive content analysis. The encouraging factors that
      emerged were involvement in the program, the time of delivery, love and care, and
      also the suspicion of corruption. The inconveniencing factors were the
      arrangements and working culture of the clinic, together with stigma and guilt. A
      lack of motivation, fear of death, socioeconomic circumstances and again the
      arrangements and working culture at the clinic were held as inhibiting factors.
      The ideas to remove inconvenient factors were maintaining a spiritual outlook on
      life, education, interaction, a good mood and a sense of meaningfulness.
      Considering such male views and paying attention to minorities in the development
      of national PMTCT of HIV Programs may enhance male participation in the process. 

PMID- 24449708
TI  - The Efficacy and Timing of Melodic Intonation Therapy in Subacute Aphasia.
AB  - Background Little is known about the efficacy of language production treatment in
      subacute severe nonfluent aphasia. Although Melodic Intonation Therapy (MIT) is a
      language production treatment for this disorder, until now MIT effect studies
      have focused on chronic aphasia. Purpose This study examines whether language
      production treatment with MIT is effective in subacute severe nonfluent aphasia.
      Methods A multicenter, randomized controlled trial was conducted in a waiting
      list control design: patients were randomly allocated to the experimental group
      (MIT) or the control group (control intervention followed by delayed MIT). In
      both groups, therapy started at 2 to 3 months poststroke and was given
      intensively (5 h/wk) during 6 weeks. In a second therapy period, the control
      group received 6 weeks of intensive MIT. The experimental group resumed their
      regular treatment. Assessment was done at baseline (T1), after the first
      intervention period (T2), and after the second intervention period (T3). Efficacy
      was evaluated at T2. The impact of delaying MIT on therapy outcome was also
      examined. Results A total of 27 participants were included: n = 16 in the
      experimental group and n = 11 in the control group. A significant effect in favor
      of MIT on language repetition was observed for trained items, with mixed results
      for untrained items. After MIT there was a significant improvement in verbal
      communication but not after the control intervention. Finally, delaying MIT was
      related to less improvement in the repetition of trained material. Conclusions In
      these patients with subacute severe nonfluent aphasia, language production
      treatment with MIT was effective. Earlier treatment may lead to greater
      improvement. 

PMID- 24449711
TI  - Transparency of health-apps for trust and decision making.

PMID- 24449709
TI  - Aquaporins: highly regulated channels controlling plant water relations.
AB  - Plant growth and development are dependent on tight regulation of water movement.
      Water diffusion across cell membranes is facilitated by aquaporins that provide
      plants with the means to rapidly and reversibly modify water permeability. This
      is done by changing aquaporin density and activity in the membrane, including
      posttranslational modifications and protein interaction that act on their
      trafficking and gating. At the whole organ level aquaporins modify water
      conductance and gradients at key "gatekeeper" cell layers that impact on whole
      plant water flow and plant water potential. In this way they may act in concert
      with stomatal regulation to determine the degree of isohydry/anisohydry.
      Molecular, physiological, and biophysical approaches have demonstrated that
      variations in root and leaf hydraulic conductivity can be accounted for by
      aquaporins but this must be integrated with anatomical considerations. This
      Update integrates these data and emphasizes the central role played by aquaporins
      in regulating plant water relations. 

PMID- 24449710
TI  - Novel roles for the polyphenol oxidase enzyme in secondary metabolism and the
      regulation of cell death in walnut.
AB  - The enzyme polyphenol oxidase (PPO) catalyzes the oxidation of phenolic compounds
      into highly reactive quinones. Polymerization of PPO-derived quinones causes the
      postharvest browning of cut or bruised fruit, but the native physiological
      functions of PPOs in undamaged, intact plant cells are not well understood.
      Walnut (Juglans regia) produces a rich array of phenolic compounds and possesses
      a single PPO enzyme, rendering it an ideal model to study PPO. We generated a
      series of PPO-silenced transgenic walnut lines that display less than 5% of wild
      type PPO activity. Strikingly, the PPO-silenced plants developed spontaneous
      necrotic lesions on their leaves in the absence of pathogen challenge (i.e. a
      lesion mimic phenotype). To gain a clearer perspective on the potential functions
      of PPO and its possible connection to cell death, we compared the leaf
      transcriptomes and metabolomes of wild-type and PPO-silenced plants. Silencing of
      PPO caused major alterations in the metabolism of phenolic compounds and their
      derivatives (e.g. coumaric acid and catechin) and in the expression of
      phenylpropanoid pathway genes. Several observed metabolic changes point to a
      direct role for PPO in the metabolism of tyrosine and in the biosynthesis of the
      hydroxycoumarin esculetin in vivo. In addition, PPO-silenced plants displayed
      massive (9-fold) increases in the tyrosine-derived metabolite tyramine, whose
      exogenous application elicits cell death in walnut and several other plant
      species. Overall, these results suggest that PPO plays a novel and fundamental
      role in secondary metabolism and acts as an indirect regulator of cell death in
      walnut. 

PMID- 24449712
TI  - Engaging with a Wiki related to knowledge translation: a survey of WhatisKT Wiki
      users.
AB  - BACKGROUND: In 2008, WhatisKT wiki was launched as a collaborative platform for
      knowledge translation (KT) researchers and stakeholders to debate the use and
      definitions of KT-related terms. The wiki has definitions for over 110 terms from
      disciplines including health care, information technology, education, accounting,
      and business. WhatisKT wiki has over 115 registered users. Approximately 73,000
      unique visitors have visited the wiki since 2008. Despite annual increases in
      visitors and regular maintenance of the wiki, no visitors have contributed
      content or started a discussion. OBJECTIVE: We surveyed wiki users to gain an
      understanding of the perceived value of the website, reasons for not engaging in
      the wiki, and suggestions to facilitate collaboration and improve the usability
      of the wiki. METHODS: We surveyed three cohorts: KT Canada members who were
      previously invited to join the wiki, registered wiki members, and unregistered
      visitors. The first two cohorts completed a Web-based survey that included the
      System Usability Scale (SUS) questionnaire to assess usability; additionally 3
      participants were interviewed. Unregistered wiki visitors were surveyed with
      polls posted on the wiki. The study received ethics approval from the McMaster
      University Faculty of Health Sciences Research Ethics Board. RESULTS: Twenty
      three participants completed the Web-based and SUS surveys; 15 participants
      indicated that they would collaborate on the wiki. The mean SUS score of 67 (95%
      CI 56-77) indicated that the wiki could be considered for design improvements.
      Study participants indicated that the wiki could be improved by email
      notification regarding new terms, better grouping of terms, user friendly
      interface, and training for users interested in editing content. CONCLUSIONS: The
      findings from this survey will be used to enhance the design and content of
      WhatisKT wiki. Further feedback from participants will be used to make the wiki
      an ideal collaboration platform for KT researchers interested in terminology.

PMID- 24449713
TI  - Evaluating positional accuracy using megavoltage cone-beam computed tomography
      for IMRT with head-and-neck cancer.
AB  - Accurate dose delivery is essential for the success of intensity-modulated
      radiation therapy (IMRT) for patients with head-and-neck (HN) cancer.
      Reproducibility of IMRT dose delivery to HN regions can be critically influenced
      by treatment-related changes in body contours. Moreover, some set-up margins may
      not be adaptable to positional uncertainties of HN structures at every treatment.
      To obtain evidence for appropriate set-up margins in various head and neck areas,
      we prospectively evaluated positional deviation (delta values) of four bony
      landmarks (i.e. the clivus and occipital protuberance for the head region, and
      the mental protuberance and C5 for the neck region) using megavoltage cone-beam
      computed tomography during a treatment course. Over 800 delta values were
      analyzed in each translational direction. Positional uncertainties for HN cancer
      patients undergoing IMRT were evaluated relative to the body mass index. Low
      positional accuracy was observed for the neck region compared with the head
      region. For the head region, most of the delta was distributed within +/- 5 mm,
      and use of the current set-up margin was appropriate. However, the delta values
      for the neck region were within +/- 8 mm. Especially for overweight patients, a
      few millimeters needed to be added to give an adequate set-up margin. For
      accurate dose delivery to targets and to avoid excess exposure to normal tissues,
      we recommend that the positional verification process be performed before every
      treatment.

PMID- 24449714
TI  - Dosimetric verification for intensity-modulated arc therapy plans by use of 2D
      diode array, radiochromic film and radiosensitive polymer gel.
AB  - Several tools are used for the dosimetric verification of intensity-modulated arc
      therapy (IMAT) treatment delivery. However, limited information is available for
      composite on-line evaluation of these tools. The purpose of this study was to
      evaluate the dosimetric verification of IMAT treatment plans using a 2D diode
      array detector (2D array), radiochromic film (RCF) and radiosensitive polymer gel
      dosimeter (RPGD). The specific verification plans were created for IMAT for two
      prostate cancer patients by use of the clinical treatment plans. Accordingly, the
      IMAT deliveries were performed with the 2D array on a gantry-mounting device, RCF
      in a cylindrical acrylic phantom, and the RPGD in two cylindrical phantoms. After
      the irradiation, the planar dose distributions from the 2D array and the RCFs,
      and the 3D dose distributions from the RPGD measurements were compared with the
      calculated dose distributions using the gamma analysis method (3% dose difference
      and 3-mm distance-to-agreement criterion), dose-dependent dose difference
      diagrams, dose difference histograms, and isodose distributions. The gamma
      passing rates of 2D array, RCFs and RPGD for one patient were 99.5%, 96.5% and
      93.7%, respectively; the corresponding values for the second patient were 97.5%,
      92.6% and 92.9%. Mean percentage differences between the RPGD measured and
      calculated doses in 3D volumes containing PTVs were -0.29 +/- 7.1% and 0.97 +/-
      7.6% for the two patients, respectively. In conclusion, IMAT prostate plans can
      be delivered with high accuracy, although the 3D measurements indicated less
      satisfactory agreement with the treatment plans, mainly due to the dosimetric
      inaccuracy in low-dose regions of the RPGD measurements. 

PMID- 24449715
TI  - A dosimetry method for low dose rate brachytherapy by EGS5 combined with
      regression to reflect source strength shortage.
AB  - The post-implantation dosimetry for brachytherapy using Monte Carlo calculation
      by EGS5 code combined with the source strength regression was investigated with
      respect to its validity. In this method, the source strength for the EGS5
      calculation was adjusted with the regression, so that the calculation would
      reproduce the dose monitored with the glass rod dosimeters (GRDs) on a water
      phantom. The experiments were performed, simulating the case where one of two
      (125)I sources of Oncoseed 6711 was lacking strength by 4-48%. As a result, the
      calculation without regression was in agreement with the GRD measurement within
      26-62%. In this case, the shortage in strength of a source was neglected. By the
      regression, in order to reflect the strength shortage, the agreement was improved
      up to 17-24%. This agreement was also comparable with accuracy of the dose
      calculation for single source geometry reported previously. These results suggest
      the validity of the dosimetry method proposed in this study. 

PMID- 24449716
TI  - Efficacy and safety of a routine early invasive strategy after fibrinolysis
      stratified by glycoprotein IIb/IIIa inhibitor use during percutaneous coronary
      intervention: a pre-specified subgroup analysis of the TRANSFER-AMI randomised
      controlled trial.
AB  - OBJECTIVE: We evaluated the efficacy and safety of an early invasive strategy
      post-fibrinolysis in relation to glycoprotein (GP) IIb/IIIa inhibitor use.
      METHODS: The Trial of Routine Angioplasty and Stenting after Fibrinolysis to
      Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomised 1059
      ST elevation myocardial infarction patients to an early invasive strategy or
      standard therapy post-fibrinolysis. The primary end point was the composite of
      death, reinfarction, recurrent ischaemia, new or worsening heart failure, or
      cardiogenic shock at 30 days. In this pre-specified analysis, we examined
      efficacy and safety outcomes of an early invasive strategy after stratification
      by GPIIb/IIIa inhibitor use, which was permitted during percutaneous coronary
      intervention (PCI) at the discretion of the treating physician. RESULTS: A total
      of 695 patients (65.6%) received GPIIb/IIIa inhibitors. There was significant
      heterogeneity (p<0.001) in the efficacy of an early invasive strategy compared to
      standard therapy, between the strata with GPIIb/IIIa inhibitor use (primary end
      point 9.6% vs 22.3% respectively, p<0.001) and without GPIIb/IIIa inhibitor use
      (primary end point 14.8% vs 10.4% respectively, p=0.21). Patients who received
      GPIIb/IIIa inhibitors had lower Global Registry of Acute Coronary Events (GRACE)
      risk scores compared to those without GPIIb/IIIa inhibitor use (median 121 vs
      130, p<0.001). After adjusting for the interaction between GRACE risk score and
      treatment assignment, the heterogeneity in the efficacy of an early invasive
      strategy with respect to GPIIb/IIIa inhibitor use was no longer significant (p
      interaction=0.08). CONCLUSIONS: The apparent difference in the efficacy of an
      early invasive strategy between GPIIb/IIIa inhibitor strata likely reflects an
      association between GPIIb/IIIa inhibitor use and baseline risk. GPIIb/IIIa
      inhibitor use during PCI at the discretion of the treating physician does not
      appear to modulate the efficacy of an early invasive strategy post-fibrinolysis.
      CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov/ct2/show/NCT00164190,
      NCT00164190.

PMID- 24449717
TI  - Significant lead-induced tricuspid regurgitation is associated with poor
      prognosis at long-term follow-up.
AB  - BACKGROUND: Although the presence of an RV lead is a potential cause of tricuspid
      regurgitation (TR), the clinical impact of significant lead-induced TR is
      unknown. OBJECTIVE: To evaluate the effect of significant lead-induced TR on
      cardiac performance and long-term outcome after cardioverter-defibrillator (ICD)
      or pacemaker implantation. METHODS: A retrospective cohort of 239 ICD (n=191) or
      pacemaker (n=48) recipients (age 60+/-14 years, 77% male) from a tertiary care
      university hospital, with an echocardiographic evaluation before and within 1-1.5
      years after device implantation were included. Significant lead-induced TR was
      defined as TR worsening, reaching a grade >=2 at follow-up echocardiography.
      During long-term follow-up (median 58, IQR 35-76 months), all-cause mortality and
      heart failure related events were recorded. RESULTS: Before device implantation,
      most patients had TR grade 1 or 2 (64.0%) or no TR (33.9%), but after lead
      placement, significant TR was seen in 91 patients (38%). Changes in cardiac
      volumes and function at follow-up were similar between patients with and without
      significant lead-induced TR, except for larger RV diastolic area (17+/-6mm(2) vs
      16+/-5mm(2), p=0.009), larger right atrial diameter (39+/-10 mm vs 36+/-8 mm,
      p<0.001) and higher pulmonary arterial pressures (41+/-15 mm Hg vs 33+/-10 mm Hg,
      p<0.001) in patients with significant lead-induced TR. Patients with significant
      lead-induced TR had worse long-term survival (HR=1.687, p=0.040) and/or more
      heart failure related events (HR=1.641, p=0.019). At multivariate analysis,
      significant lead-induced TR was independently associated with all-cause mortality
      (HR=1.749, p=0.047) together with age, LVEF and percentage RV pacing.
      CONCLUSIONS: Significant lead-induced TR is associated with poor long-term
      prognosis.

PMID- 24449718
TI  - Mitochondrial cytopathies and cardiovascular disease.
AB  - The global epidemic of cardiovascular disease remains the leading cause of death
      in the USA and across the world. Functional and structural integrity of
      mitochondria are essential for the physiological function of the cardiovascular
      system. The metabolic adaptation observed in normal heart is lost in the failing
      myocardium, which becomes progressively energy depleted leading to impaired
      myocardial contraction and relaxation. Uncoupling of electron transfer from ATP
      synthesis leads to excess generation of reactive species, leading to widespread
      cellular injury and cardiovascular disease. Accumulation of mitochondrial DNA
      mutation has been linked to ischaemic heart disease, cardiomyopathy and
      atherosclerotic vascular disease. Mitochondria are known to regulate apoptotic
      and autophagic pathways that have been shown to play an important role in the
      development of cardiomyopathy and atherosclerosis. A number of pharmacological
      and non-pharmacological treatment options have been explored in the management of
      mitochondrial diseases with variable success.

PMID- 24449719
TI  - Cardiac output response and peripheral oxygen extraction during exercise among
      symptomatic hypertrophic cardiomyopathy patients with and without left
      ventricular outflow tract obstruction.
AB  - OBJECTIVE: Reduction of left ventricular outflow tract obstruction (LVOTO) often
      improves symptoms in hypertrophic cardiomyopathy (HCM), but the correlation
      between exercise performance and measured LVOT gradients is weak. We investigated
      the relationship between LVOTO and cardiorespiratory responses during exercise.
      METHODS: The study cohort included 70 patients with HCM (32 with LVOTO, 55 male,
      age 47+/-13) attending a dedicated cardiomyopathy clinic and 28 normal
      volunteers. All underwent cardiopulmonary exercise testing with simultaneous non
      invasive haemodynamic assessment using finger plethysmography. Main outcome
      measures were peak oxygen consumption, cardiac index and arteriovenous oxygen
      difference. RESULTS: When compared with controls, patients had reduced peak
      exercise oxygen consumption (22.4+/-6.1 vs 34.7+/-7.7 mL/kg/min, p<0.0001) and
      cardiac index (5.5+/-1.9 vs 9.4+/-2.9 L/min/m(2), p<0.0001). At all workloads,
      stroke volume index (SVI) was lower and arteriovenous oxygen difference greater
      in patients. During all stages of exercise, LVOTO in patients was associated with
      failure to augment SVI and higher oxygen consumption; cardiac reserve (4.4+/-2.7
      vs 6.3+/-3.6 L/min, p=0.025) and peak mean arterial pressure (104+/-16 vs 112+/
      16 mm Hg, p=0.033) were lower. Multivariable predictors of cardiac output
      response were age (beta: -0.11; CI -0.162 to -0.057; p<0.0001), peak LVOT
      gradient (beta: -0.018; CI -0.034 to -0.002; p=0.031) and gender (beta: -2.286;
      CI -0.162 to -0.577; p=0.01). Within the obstructive cohort, different patterns
      of SV response were elicited in patients with similar clinical features.
      CONCLUSIONS: Cardiac reserve is reduced in HCM because of failure of SV
      augmentation. LVOTO exacerbates this abnormal response, but haemodynamic
      responses vary significantly. Non-invasive exercise haemodynamic assessment may
      improve understanding of symptoms and help tailor therapy.

PMID- 24449720
TI  - Consensus report on the detailed fetal anatomic ultrasound examination:
      indications, components, and qualifications.

PMID- 24449721
TI  - Shear wave elastography for evaluation of liver fibrosis.
AB  - The prognosis and management of chronic viral hepatitis mainly depend on the
      extent of liver fibrosis, particularly in chronic hepatitis C. Liver histologic
      analysis is still considered the reference standard in the assessment of liver
      fibrosis despite the interobserver and interobserver variability in staging and
      some morbidity and mortality risks. Thus, noninvasive methods for assessing liver
      fibrosis are of great clinical interest. In the last decade, ultrasound-based
      techniques to estimate the stage of liver fibrosis have become commercially
      available. They all have the capability to noninvasively evaluate differences in
      the elastic properties of soft tissues by measuring tissue behavior when a
      mechanical stress is applied. Shear wave elastography relies on the generation of
      shear waves determined by the displacement of tissues induced by the force of a
      focused ultrasound beam or by an external push. This article reviews the results
      that have been obtained with shear wave elastography for assessment of liver
      fibrosis. 

PMID- 24449722
TI  - Diagnostic performance of contrast-enhanced sonography and acoustic radiation
      force impulse imaging in solid liver lesions.
AB  - OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance
      of contrast-enhanced sonography and acoustic radiation force impulse imaging
      (ARFI) in differential diagnosis of benign and malignant liver lesions. METHODS:
      A total of 156 patients with liver lesions were included in the study. The images
      from conventional sonography and contrast-enhanced sonography and the shear wave
      velocity values of the liver lesions were obtained. The diagnostic performance of
      conventional sonography, contrast-enhanced sonography, and ARFI was assessed by
      using pathologic examination (needle biopsy or surgery) or clinical imaging
      inspection as the reference standard. RESULTS: The sensitivity and specificity of
      conventional sonography for malignant liver lesions were 57.1% and 43.1%,
      respectively, and the sensitivity and specificity of ARFI were 81.3% and 74.1%.
      When using contrast-enhanced sonography for the diagnosis of malignant liver
      lesions, the sensitivity and specificity were 92.9% and 89.7%. The sensitivity
      and specificity of contrast-enhanced sonography were significantly higher than
      those of ARFI and conventional sonography (P < .05). CONCLUSIONS: The
      differential diagnostic performance of contrast-enhanced sonography is most
      predictive of malignant liver lesions. Contrast-enhanced sonography and ARFI have
      complementary effects in the differential diagnosis of benign and malignant liver
      lesions.

PMID- 24449723
TI  - Contribution of contrast-enhanced sonography in the detection of intrahepatic
      cholangiocarcinoma.
AB  - OBJECTIVES: The purpose of this study was to evaluate the contribution of
      contrast-enhanced sonography in the diagnosis of intrahepatic cholangiocarcinoma
      up to 3 cm and analyze its dynamic enhancement patterns. METHODS: Forty-five
      patients (29 male and 16 female; mean age +/- SD, 61.3 +/- 10.7 years; range, 38
      79 years) with a preliminary diagnosis of intrahepatic cholangiocarcinoma by
      contrast-enhanced sonography were retrospectively analyzed. For each nodule, the
      enhancement pattern, level, and dynamic change during the arterial, portal, and
      late phases after the injection of a sulfur hexafluoride microbubble contrast
      agent were evaluated. RESULTS: Among the 35 patients with a histopathologic
      diagnosis of intrahepatic cholangiocarcinoma, 18 nodules showed hyperenhancement
      during the arterial phase, and 17 showed hypoenhancement. Heterogeneous,
      peripheral, and partial enhancement were found in 24, 8, and 2 nodules,
      respectively. However, only 1 nodule showed homogeneous enhancement. During the
      portal phase, 34 nodules showed hypoenhancement, and 1 showed isoenhancement.
      Hypoenhancement during the late phase was observed in all cases. Ten patients had
      a misdiagnosis of intrahepatic cholangiocarcinoma. CONCLUSIONS: Intrahepatic
      cholangiocarcinoma up to 3 cm may display a variety of arterial enhancement
      patterns on contrast-enhanced sonography. However, some other nodules may
      manifest findings similar to those of intrahepatic cholangiocarcinoma.

PMID- 24449724
TI  - Sonographic features of thyroid follicular carcinoma in comparison with thyroid
      follicular adenoma.
AB  - OBJECTIVES: The purpose of this study was to determine the sonographic features
      of thyroid follicular carcinoma in comparison with thyroid follicular adenoma.
      METHODS: This retrospective study included 36 pathologically proven follicular
      carcinomas (5 widely invasive and 31 minimally invasive) and 52 follicular
      adenomas in 88 patients who underwent thyroid surgery. We analyzed the
      sonographic features of each tumor, including maximum diameter, peripheral halo,
      echogenicity, echo texture, calcifications, and nodularity. The frequencies of
      the sonographic features were compared by chi(2) and Fisher exact tests between
      follicular adenomas and carcinomas. The relative risk of malignancy was evaluated
      by logistic regression analysis. RESULTS: Predominantly solid contents,
      hypoechoic echogenicity, a heterogeneous echo texture, the presence of
      calcifications, and an absent or irregular thick halo were associated with
      follicular carcinoma (P < .05). Logistic regression analysis demonstrated that
      predominantly solid contents, a heterogeneous echo texture, and the presence of
      calcifications were associated with significant increases in the relative risk of
      follicular carcinoma (odds ratios, 9.4, 24.9, and 25.6, respectively; P < .01).
      CONCLUSIONS: Sonography could provide useful information for differentiating
      follicular carcinoma from follicular adenoma.

PMID- 24449725
TI  - Predictive factors for extrathyroidal extension of papillary thyroid carcinoma
      based on preoperative sonography.
AB  - OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance
      and predictive factors of extrathyroidal extension of papillary thyroid carcinoma
      based on preoperative sonography. METHODS: Preoperative sonography was performed
      for 568 patients who underwent surgery for papillary thyroid cancer between May
      2009 and December 2010. Patients' T stages based on preoperative sonography were
      compared with their T stages based on pathologic examination, and we
      statistically analyzed the discriminatory performance of sonography. Among the
      568 patients enrolled in this study, we selected 320 patients in whom
      extrathyroidal extension was suspected on sonography. We analyzed several
      predictive factors for extrathyroidal extension. RESULTS: Two hundred seventy
      five of the 568 patients were proven to have pathologic extrathyroidal extension
      of papillary thyroid cancer after surgery (75.9% diagnostic accuracy, 83.3%
      sensitivity, 68.9% specificity, 71.6% positive predictive value, and 81.5%
      negative predictive value). Of 320 patients with sonographically suspected
      extrathyroidal extension, a larger lesion size (P < .001) and a higher lymph node
      stage on sonography (P = .004) were the best predictors of extrathyroidal
      extension among the features that we measured. There were no significant
      differences in terms of the lesion site or thyroid parenchymal background
      echogenicity. Thyroid capsular protrusion had a higher predictive value than the
      abutting ratio (P = .001). However, increasing the abutting ratio enabled the
      prediction of extrathyroidal extension on sonography (P = .009). CONCLUSIONS:
      Preoperative sonography is a helpful tool for predicting pathologic
      extrathyroidal extension of papillary thyroid cancer. In particular, clinicians
      should focus on the lesion size, nodal stage, and abutment or capsular protrusion
      of the lesion while performing sonography because these are the most useful
      predictive factors for extrathyroidal extension.

PMID- 24449726
TI  - Sonographic detection of thyroid pyramidal lobes before thyroid surgery: a
      prospective single-center study.
AB  - OBJECTIVES: This study aimed to assess the rate of preoperative sonographic
      detection of thyroid pyramidal lobes with subsequent surgical findings as the
      reference standard. METHODS: From January 2013 to March 2013, a single
      radiologist prospectively performed thyroid sonography to detect thyroid
      pyramidal lobes in consecutive patients who were scheduled for thyroid surgery on
      the same day. The location, anteroposterior and transverse diameters, length, and
      location of the upper end of each thyroid pyramidal lobe and its separation or
      contiguity with the main thyroid gland were investigated by thyroid sonography
      and surgery. RESULTS: The types of thyroid surgery included total thyroidectomy
      (n = 85), subtotal thyroidectomy (n = 4), and hemithyroidectomy (n = 43). The
      surgical incidence of thyroid pyramidal lobes was 59.8% (79 of 132), and the
      sensitivity, specificity, positive and negative predictive values, and accuracy
      of sonography for detection of thyroid pyramidal lobes were 81.0%, 79.2%, 85.3%,
      73.7%, and 80.3%, respectively. The mean values for the anteroposterior diameter,
      transverse diameter, and length of the 79 thyroid pyramidal lobes at surgery were
      2.2, 6.2, and 26.5 mm, respectively, but these measurements did not show
      statistically significant correlations with the sonographic detection rate of
      thyroid pyramidal lobes. CONCLUSIONS: Our study indicates that thyroid sonography
      may be helpful for identifying the presence and location of thyroid pyramidal
      lobes.

PMID- 24449727
TI  - Computer-aided diagnostic system for detection of Hashimoto thyroiditis on
      ultrasound images from a Polish population.
AB  - OBJECTIVES: Computer-aided diagnostic (CAD) techniques aid physicians in better
      diagnosis of diseases by extracting objective and accurate diagnostic information
      from medical data. Hashimoto thyroiditis is the most common type of inflammation
      of the thyroid gland. The inflammation changes the structure of the thyroid
      tissue, and these changes are reflected as echogenic changes on ultrasound
      images. In this work, we propose a novel CAD system (a class of systems called
      ThyroScan) that extracts textural features from a thyroid sonogram and uses them
      to aid in the detection of Hashimoto thyroiditis. METHODS: In this paradigm, we
      extracted grayscale features based on stationary wavelet transform from 232
      normal and 294 Hashimoto thyroiditis-affected thyroid ultrasound images obtained
      from a Polish population. Significant features were selected using a Student t
      test. The resulting feature vectors were used to build and evaluate the following
      4 classifiers using a 10-fold stratified cross-validation technique: support
      vector machine, decision tree, fuzzy classifier, and K-nearest neighbor. RESULTS:
      Using 7 significant features that characterized the textural changes in the
      images, the fuzzy classifier had the highest classification accuracy of 84.6%,
      sensitivity of 82.8%, specificity of 87.0%, and a positive predictive value of
      88.9%. CONCLUSIONS: The proposed ThyroScan CAD system uses novel features to
      noninvasively detect the presence of Hashimoto thyroiditis on ultrasound images.
      Compared to manual interpretations of ultrasound images, the CAD system offers a
      more objective interpretation of the nature of the thyroid. The preliminary
      results presented in this work indicate the possibility of using such a CAD
      system in a clinical setting after evaluating it with larger databases in
      multicenter clinical trials.

PMID- 24449728
TI  - Combined value of Virtual Touch tissue quantification and conventional
      sonographic features for differentiating benign and malignant thyroid nodules
      smaller than 10 mm.
AB  - OBJECTIVES: This study aimed to investigate the value of sonographic features
      including Virtual Touch tissue quantification (VTQ; Siemens Medical Solutions,
      Mountain View, CA) for differentiating benign and malignant thyroid nodules
      smaller than 10 mm. METHODS: Seventy-one thyroid nodules smaller than 10 mm with
      pathologic diagnoses were included in this study. The conventional sonographic
      features and quantitative elasticity features (VTQ) were observed and compared
      between benign and malignant nodules. RESULTS: There were 39 benign and 32
      malignant nodules according to histopathologic examination. When compared with
      benign nodules, malignant nodules were more frequently taller than wide, poorly
      defined, and markedly hypoechoic (P < .05). Color Doppler sonographic features
      were not significantly different between benign and malignant nodules. The VTQ
      value for malignant nodules (mean +/- SD 3.260 +/- 0.725 m/s) was significantly
      higher than that of benign ones (2.108 +/- 0.455 m/s; P < .001). The cutoff point
      for the differential diagnosis was 2.910 m/s, with sensitivity, specificity, a
      positive predictive value, a negative predictive value, and diagnostic accuracy
      of 71.9%, 100%, 100%, 81.2%, and 87.3% respectively. Logistic regression analysis
      showed that a taller-than-wide shape, a poorly defined boundary, marked
      hypoechogenicity, and a VTQ value greater than 2.910 m/s were independent risk
      factors for malignancy, with odds ratios of 69.366, 41.864, 5.945, and 64.991.
      The combination of VTQ with a taller-than-wide shape had the highest sensitivity
      and specificity of 90.6% and 97.4%. CONCLUSIONS: The shape, margin, echogenicity,
      and VTQ value are useful sonographic criteria for differentiating benign and
      malignant thyroid nodules smaller than 10 mm. When VTQ was combined with B-mode
      sonographic features, the sensitivity was improved significantly.

PMID- 24449729
TI  - Evaluation of a new 3-dimensional color Doppler flow method to quantify flow
      across the mitral valve and in the left ventricular outflow tract: an in vitro
      study.
AB  - OBJECTIVES: The aim of this study was to assess the accuracy, feasibility, and
      reproducibility of determining stroke volume from a novel 3-dimensional (3D)
      color Doppler flow quantification method for mitral valve (MV) inflow and left
      ventricular outflow tract (LVOT) outflow at different stroke volumes when
      compared with the actual flow rate in a pumped porcine cardiac model. METHODS:
      Thirteen freshly harvested pig hearts were studied in a water tank. We inserted a
      latex balloon into each left ventricle from the MV annulus to the LVOT, which
      were passively pumped at different stroke volumes (30-80 mL) using a calibrated
      piston pump at increments of 10 mL. Four-dimensional flow volumes were obtained
      without electrocardiographic gating. The digital imaging data were analyzed
      offline using prototype software. Two hemispheric flow-sampling planes for color
      Doppler velocity measurements were placed at the MV annulus and LVOT. The
      software computed the flow volumes at the MV annulus and LVOT within the user
      defined volume and cardiac cycle. RESULTS: This novel 3D Doppler flow
      quantification method detected incremental increases in MV inflow and LVOT
      outflow in close agreement with pumped stroke volumes (MV inflow, r = 0.96; LVOT
      outflow, r = 0.96; P < .01). Bland-Altman analysis demonstrated overestimation of
      both (MV inflow, 5.42 mL; LVOT outflow, 4.46 mL) with 95% of points within 95%
      limits of agreement. Interobserver variability values showed good agreement for
      all stroke volumes at both the MV annulus and LVOT. CONCLUSIONS: This study has
      shown that the 3D color Doppler flow quantification method we used is able to
      compute stroke volumes accurately at the MV annulus and LVOT in the same cardiac
      cycle without electrocardiographic gating. This method may be valuable for
      assessment of cardiac output in clinical studies.

PMID- 24449730
TI  - Comparison of transcranial color-coded real-time sonography and contrast-enhanced
      color-coded sonography for detection and characterization of intracranial
      arteriovenous malformations.
AB  - OBJECTIVES: To compare the diagnostic value of transcranial color-coded real-time
      sonography and contrast-enhanced color-coded sonography in detection and
      characterization of intracranial arteriovenous malformations. METHODS: Thirty-one
      patients highly suspected to have an intracranial arteriovenous malformation were
      imaged with real-time and contrast-enhanced sonography. With digital subtraction
      angiography as the reference standard, the ability to detect the malformations
      and accurately determine their size and location was compared between the two
      imaging techniques. RESULTS: One cavernous hemangioma and 30 intracranial
      arteriovenous malformations were imaged with real-time and contrast-enhanced
      sonography, which were confirmed by angiography. The detectability of contrast
      enhanced sonography, especially for optimizing visualization of malformations
      located in the frontal, parietal, and occipital lobes, was higher than that of
      real-time sonography, although the overall number of malformations was too small
      to demonstrate significance. The sizes of the malformations (6 in the frontal
      lobe, 1 in the parietal lobe, and 1 in the occipital lobe) were underestimated by
      real-time sonography compared to angiography, whereas there was agreement in the
      sizes between contrast-enhanced sonography and angiography. The detection rates
      for the 30 arteriovenous malformations on contrast-enhanced and real-time
      sonography were 96.7% (29 of 30) and 70.0% (21 of 30), respectively (P = .008).
      Moreover, contrast-enhanced sonography was significantly superior to real-time
      sonography for detection of feeding arteries (59.5% [22 of 37] versus 83.7% [31
      of 37]; P = .004). Although the feeding arteries showed increased peak systolic
      and end-diastolic velocities after contrast agent injection, there were no
      statistically significant differences in the velocities before and after
      injection. CONCLUSIONS: Transcranial contrast-enhanced color-coded sonography is
      superior to color-coded real-time sonography for detection of intracranial
      arteriovenous malformations, particularly for lesions located in the frontal,
      parietal, and occipital lobes of the brain.

PMID- 24449731
TI  - Sex differences between vascular endothelial function and carotid intima-media
      thickness by Framingham Risk Score.
AB  - OBJECTIVES: To investigate sex differences associated with changes in brachial
      artery flow-mediated dilatation and carotid intima-media thickness by Framingham
      Risk Score. METHODS: The study included 1083 patients aged 30 to 80 years.
      According to the Framingham Risk Score, patients were divided into 3 groups: low,
      mid, and high risk. Traditional cardiovascular risk factors such as age, sex,
      smoking, diabetes, hypertension, and cholesterol were assessed by Framingham Risk
      Score, as well as laboratory and vascular parameters, including flow-mediated
      dilatation and intima-media thickness. Correlations between flow-mediated
      dilatation, intima-media thickness, and the Framingham Risk Score were analyzed
      by sex. RESULTS: Compared with women, flow-mediated dilatation in men was
      significantly lower in the low-risk group (mean +/- SD, 8.31% +/- 2.89% versus
      9.76% +/- 3.62%; P< .001) but significantly higher in the mid- and high-risk
      groups (mid-risk, 7.43% +/- 2.65% versus 6.67% +/- 2.42%; high-risk, 6.41% +/-
      2.27% versus 5.78% +/- 2.39%; P< .001). Flow-mediated dilatation decreased with
      an increasing Framingham Risk Score in both sexes but especially in women.
      Although intima-media thickness increased with the Framingham Risk Score in both
      sexes, there was no significant sex difference between the groups. Univariate
      analysis showed significant negative correlations between flow-mediated
      dilatation and the Framingham Risk Score in both sexes (R men = -0.308; P < .001;
      R women = -0.572; P < .001) and flow-mediated dilatation and intima-media
      thickness (R men = -0.295; P < .001; R women = -0.474; P< .001). There was a
      significant positive correlation between intima-media thickness and the
      Framingham Risk Score (R men = 0.571; P< .001; R women = 0.633; P < .001).
      CONCLUSIONS: A sex difference existed only for flow-mediated dilatation at the
      same Framingham risk level. Flow-mediated dilatation might be more sensitive than
      intima-media thickness for detecting sex differences in vascular dysfunction,
      according to Framingham risk stratification in a Chinese population.

PMID- 24449732
TI  - Quantitative assessment of left ventricular function by 3-dimensional speckle
      tracking echocardiography in patients with chronic heart failure: a meta
      analysis.
AB  - OBJECTIVES: To provide a comprehensive analysis of the clinical utility of 3
      dimensional (3D) speckle-tracking echocardiography for left ventricular (LV)
      function in patients with chronic heart failure (CHF). METHODS: Literature
      searches were conducted in the PubMed, Embase, Web of Science, and China
      BioMedicine databases on relevant articles published before October 1, 2012.
      Crude standardized mean differences with 95% confidence intervals (CIs) were
      calculated. RESULTS: Seven case-control studies were included with a total of 375
      patients with CHF and 181 healthy control participants. Meta-analysis results
      showed that the LV ejection fraction in the patients was significantly lower than
      in the controls (standardized mean difference, -4.62; 95% CI, -6.19 to -3.04),
      whereas the LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) in
      the patients were higher than in the controls (LVEDV: standardized mean
      difference, 1.76; 95% CI, 1.09 to 2.44; LVESV: standardized mean difference,
      2.04, 95% CI, 1.30 to 2.78). The results also indicated that the patients had a
      greater delay in the standard deviation of the time to peak area tracking and the
      maximum difference in the time to peak area tracking in the 16 LV segments than
      the controls (standard deviation of the time to peak area tracking: standardized
      mean difference, 3.01; 95% CI, 1.73 to 4.29; maximum difference in the time to
      peak area tracking: standardized mean difference, 3.26; 95% CI, 1.58 to 4.93).
      Furthermore, global longitudinal, circumferential, and radial strain were also
      significantly impaired in the patients compared to the controls (longitudinal
      strain: standardized mean difference, 2.75; 95% CI, 1.11 to 4.39; circumferential
      strain: standardized mean difference, 2.71; 95% CI, 1.15 to 4.27; radial strain:
      standardized mean difference, 1.80; 95% CI, 0.45 to 3.14). CONCLUSIONS: This meta
      analysis suggests that LV function in patients with CHF can be noninvasively and
      objectively measured by 3D speckle-tracking echocardiography.

PMID- 24449733
TI  - Image quality influences the assessment of left ventricular function: an
      intraoperative comparison of five 2-dimensional echocardiographic methods with
      real-time 3-dimensional echocardiography as a reference.
AB  - OBJECTIVES: Transesophageal echocardiography has become a standard tool for
      evaluating left ventricular function during cardiac surgery. However, the image
      quality varies widely between patients and examinations. The aim of this study
      was to investigate the influence of the image quality on 5 commonly used 2
      dimensional methods. METHODS: Transesophageal real-time 3-dimensional
      echocardiography (3DE) served as a reference. Left ventricular function was
      evaluated in 63 patients with sufficient real-time 3DE image quality. The image
      quality was rated using the ratio of the visualized border divided by the total
      endocardial border. These ratings were used to generate groups of poor (0%-40%),
      fair (41%-70%), and good (71%-100%) image quality. The ejection fraction (EF),
      end-diastolic volume, and end-systolic volume were analyzed by the Simpson method
      of disks (biplane and monoplane), eyeball method, Teichholz method, and speckle
      tracking method. Furthermore, the fractional area change was determined. Each
      correlation with real-time 3DE was evaluated. RESULTS: Correlations of the EF and
      volumes, respectively, as determined by long-axis view methods increased with
      improving image quality: the Simpson biplane method was found to be the most
      accurate method, with good image quality for the EF (r = 0.946) and volumes (end
      diastolic volume, r = 0.962; end-systolic volume, r = 0.989). Correlations of the
      EF and fractional area change by short-axis view methods decreased with improving
      image quality, with the Teichholz EF found to be most accurate with poor (r =
      0.928) in contrast to good (r = 0.699) image quality. CONCLUSIONS: With good
      image quality, the Simpson biplane method is the most accurate 2-dimensional
      method for assessing the left ventricular EF. Short-axis view methods, especially
      the Teichholz method yield better correlations with poor image quality. The
      eyeball method was unaffected by image quality.

PMID- 24449734
TI  - Early screening for cardiovascular abnormalities with preparticipation
      echocardiography: utility of focused physician-operated echocardiography in
      preparticipation screening of athletes.
AB  - OBJECTIVES: We have developed the Early Screening for Cardiovascular
      Abnormalities With Preparticipation Echocardiography protocol to improve false
      positive rates, reduce referrals, and broaden the spectrum of disease that can be
      captured through preparticipation screening of athletes. This study documents the
      first application of this protocol and uses case analysis to discuss the
      potential utility of portable sonography in screening. METHODS: Sixty-five male
      collegiate athletes, aged 18 to 25 years, were prospectively enrolled. Each
      athlete was screened with a history and physical examination, electrocardiography
      (ECG), and focused echocardiography performed by a noncardiologist sports
      medicine physician. The history and physical examination were based on the 12
      element American Heart Association recommendations; 2010 European Society of
      Cardiology criteria were used to screen ECGs. Focused physician-operated
      echocardiography was performed to assess for hypertrophic cardiomyopathy and
      aortic root dilatation. Athletes screening positive were referred to a
      cardiologist. RESULTS: Most of the athletes (n = 59) did not screen positive by
      any screening modality. Three athletes screened positive on ECG but had normal
      focused echocardiographic findings. Three athletes screened positive by history
      and physical examination but had normal ECG and focused echocardiographic
      findings. All athletes screening positive were referred to a cardiologist and
      eventually cleared for sports participation. No athlete screened positive by
      focused echocardiography alone. Focused echocardiography was able to reduce the
      referral rate for hypertrophic cardiomyopathy by 33% and obtained measurements
      statistically similar to those of formal echocardiography. CONCLUSIONS: This
      study provides evidence that focused physician-operated echocardiography can
      improve false-positive rates and broaden the spectrum of disease that is
      detectable through preparticipation screening of athletes.

PMID- 24449735
TI  - Extended transvaginal sonography in deep infiltrating endometriosis: use of bowel
      preparation and an acoustic window with intravaginal gel: preliminary results.
AB  - OBJECTIVES: The purpose of this study was to assess the diagnostic performance of
      extended transvaginal sonography for diagnosing deep infiltrating endometriosis.
      METHODS: A prospective study was conducted comprising 51 women (mean age, 32.9
      years; range, 23-43 years) with suspected deep infiltrating endometriosis based
      on clinical symptoms. All women underwent extended transvaginal sonography, which
      included assessment of 2 pelvic compartments (anterior compartment: bladder and
      distal ureters; and posterior compartment: posterior vaginal fornix,
      retrocervical area, pouch of Douglas, and rectosigmoid). The sliding sign for
      detecting pouch of Douglas obliteration was also assessed. All patients received
      bowel preparation before sonographic examinations. A single examiner performed
      all examinations. All women underwent laparoscopic surgery, and histologic
      confirmation of endometriosis was done. The sensitivity, specificity, positive
      likelihood ratio (LR+) and negative likelihood ratio (LR-) were calculated.
      RESULTS: Some women had more than 1 lesion, giving a total of 55 histologically
      confirmed lesions (rectosigmoid, n = 13; vagina, n = 5; retrocervical, n = 32;
      bladder, n = 5). The sensitivity, specificity, and LR+ for rectosigmoid
      involvement were 100%, 93%, and 14.0, respectively. The sensitivity, specificity,
      LR+, and LR- for vaginal involvement were 60%, 98%, 30.0, and 0.41. The
      sensitivity, specificity, LR+, and LR- for retrocervical involvement were 84%,
      96%, 19.4, and 0.16. The sensitivity, specificity, and LR- for bladder
      involvement were 20%, 100%, and 0.80. The sensitivity, specificity, LR+, and LR-
      of the sliding sign for diagnosing pouch of Douglas obliteration were 89%, 92%,
      10.7, and 0.12. CONCLUSIONS: Except for bladder involvement, extended
      transvaginal sonography has good diagnostic performance for deep infiltrating
      endometriosis.

PMID- 24449736
TI  - Orientation of the uterine fundus in reference to the longitudinal axis of the
      body: a 3-dimensional sonographic study.
AB  - OBJECTIVES: The aim of this pilot study was to measure the angle of rotation of
      the uterus at the fundus from horizontal using 3-dimensional sonography in women
      presenting for annual gynecologic examinations. METHODS: A total of 51 patients
      participated in the study. All patients underwent transvaginal sonography, and 3
      dimensional volumes were acquired. The cervicouterine angle and the angle of
      rotation at the fundus were measured. RESULTS: The uteri were noted to be
      anteverted in 64.7%, retroverted in 25.5%, and euverted in 9.8%. They were noted
      to be pointing toward the right side of the pelvis in 49.0%, to the left side in
      39.2%, and at the midline in 11.8%. The median cervicouterine angle was 122
      degrees  (interquartile range [IQR], 105 degrees -137 degrees ). The median angle
      of rotation at the fundus away from horizontal in either a clockwise or
      counterclockwise direction on the transverse B-plane was 10.4 degrees  (IQR, 7.1
      degrees -19.0 degrees ), with a maximal angle of 43 degrees , and on the coronal
      C-plane, it was 10.0 degrees  (IQR, 3.0 degrees -20.0 degrees ), with a maximal
      angle of 43 degrees . Noneuverted uteri were more likely to be rotated at the
      fundus. CONCLUSIONS: Our study reveals that, contrary to traditional thinking,
      the uterus can be rotated at the fundus in relation to the body (z-axis) along
      the longitudinal axis of the cervical canal.

PMID- 24449737
TI  - Reference ranges for ductus venosus velocity ratios in pregnancies with normal
      outcomes.
AB  - OBJECTIVES: The purpose of this study was to establish reference ranges for
      ductus venosus velocity ratios. METHODS: Singleton pregnancies from 11 to 38
      weeks with exactly established gestational ages (GAs) were recruited for the
      study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical
      complications, stillbirth, birth weight below the 10th or above the 90th
      percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility
      index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a,
      where S indicates ventricular systole [s-wave], v, ventricular end-systolic
      relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a,
      active ventricular filling during atrial systole [a-wave]) were calculated.
      Separate regression models were fitted to estimate the mean and standard
      deviation at each GA for each ratio. RESULTS: A total of 902 velocity wave ratios
      and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D
      ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a
      ratios were reduced with GA (P < .0001 for all). Significant reductions in the
      means and standard deviations of the PIV and S/a, v/a, and D/a ratios were
      observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately
      created between 11 and 17 weeks and 18 and 38 weeks. CONCLUSIONS: We created
      reference ranges for ductus venosus velocity ratios between 11 and 38 weeks'
      gestation in normal pregnancies. These reference ranges may prove beneficial for
      evaluation of fetal conditions that are associated with cardiovascular
      abnormalities.

PMID- 24449738
TI  - Potassium chloride-induced fetal demise: a retrospective cohort study of efficacy
      and safety.
AB  - OBJECTIVES: Induction of fetal demise before second-trimester termination is
      performed for a number of reasons. One method for inducing fetal demise is via
      sonographically guided intracardiac potassium chloride (KCl) injection. We
      performed a retrospective cohort study to determine the efficacy and safety of
      intracardiac KCl injection as a method of second-trimester induced fetal demise.
      METHODS: We reviewed records from patients who were referred for induced fetal
      demise from October 2002 to October 2011. We excluded patients undergoing
      selective fetal reduction in multiple gestations. Procedural complications, the
      dose of KCl, and the number of failed procedures were determined. RESULTS: Of the
      192 completed procedures, 191 were successful (99.5%). The median gestational age
      at termination was 22 weeks (range, 15.4-24.9 weeks), and most terminations were
      surgical (68.0%). Major indications for termination were fetal anomalies (41.6%),
      unwanted pregnancy (20.8%), and aneuploidy (15.7%). The median dose of KCl was 10
      mL (range, 3-40 mL). We found a significant correlation between the dose of KCl
      and estimated fetal weight. There was no significant correlation between the dose
      of KCl and body mass index or gestational age. We had 1 maternal complication of
      a seizure after needle placement but before KCl injection. CONCLUSIONS:
      Intracardiac KCl injection is an effective and safe method for induced fetal
      demise.

PMID- 24449739
TI  - Use of cerclage in triplet pregnancies with an asymptomatic short cervix.
AB  - OBJECTIVES: The purpose of this study was to compare the outcomes of triplet
      pregnancies in women with asymptomatic cervical shortening with and without a
      cervical cerclage. METHODS: A retrospective review of all triplet pregnancies
      with biweekly serial cervical length surveillance was performed. Cervical
      shortening was defined as a cervical length of 2.5 cm or less before 24 weeks'
      gestation. Patients with cervical shortening managed with cerclage were compared
      to those managed expectantly. The primary outcome was the gestational age at
      delivery, with secondary outcomes including birth weight, neonatal intensive care
      unit length of stay, and composite neonatal outcome. Statistical significance was
      defined as P < .05. RESULTS: Sixteen patients underwent cerclage placement versus
      8 managed expectantly (control group). The median gestational ages at delivery
      were similar between the groups (cerclage, 31.3 weeks; interquartile range [IQR],
      29.3-32.3 weeks; control, 29.8 weeks; IQR, 27.5-32.4 weeks; P = .71). The median
      birth weights were also similar between the groups (cerclage, 1283 g; IQR, 800
      1626 g; control, 1109 g; IQR, 776-1500 g; P = .54). There was no significant
      difference in composite neonatal outcomes between the cerclage and control groups
      (P = .67). CONCLUSIONS: In this limited case-control study, we found no benefit
      in terms of pregnancy prolongation or neonatal outcomes with cerclage placement
      for triplet gestations complicated by an asymptomatic short cervix.

PMID- 24449740
TI  - Fetal left ventricular mass determination on 2-dimensional echocardiography using
      area-length calculation methods.
AB  - OBJECTIVES: Fetal cardiac examination is an important part of fetal malformation
      screening. The purposes of this study were to describe the left ventricular (LV)
      mass in the second and third trimesters by 2-dimensional echocardiography using
      area-length calculation methods and to examine the clinical usefulness of this
      procedure in evaluation of gestational age (GA)- and fetal weight-related LV mass
      changes. METHODS: Five hundred healthy fetuses were divided into 2 groups (250
      participants per group): second- and third-trimester groups. The estimated fetal
      weight (EFW) was computed according to the Hadlock formula (Radiology 1984;
      150:535-540). The LV mass at end diastole (LVd mass) and LV mass at end systole
      (LVs mass) were measured, and the difference between the LVd mass and LVs mass
      [LV(d-s) mass], LVd mass/EFW ratio, and LVs mass/EFW ratio were calculated.
      RESULTS: The EFW, LVd mass, LVs mass, and LV(d-s) mass were all significantly
      greater in the third-trimester group than the second-trimester group (P < .05),
      whereas the LVd mass/EFW and LVs mass/EFW ratios did not differ between the
      groups (P > .05). The LVd mass, LVs mass, and LV(d-s) mass all significantly
      correlated with GA and weight (P< .001), but the LVd mass/EFW and LVs mass/EFW
      ratios did not (P > .05). CONCLUSIONS: Two-dimensional echocardiography using
      area-length calculation methods can effectively provide measurements for LV mass
      and can sensitively indicate fetal weight- and GA -related changes in LV mass.
      Fetal cardiac mass measurement is a useful parameter for evaluation of fetal
      heart development.

PMID- 24449741
TI  - Making chorionic villus sampling painless for both the patient and the physician.
AB  - Currently, in common practice, no pain control is provided to the patient
      undergoing transvaginal chorionic villus sampling (CVS). Chorionic villus
      sampling is an invasive procedure involving an 18-gauge needle stick through the
      abdomen or passage of a suction catheter through the cervix. Furthermore, CVS is
      a mechanically difficult procedure for the clinician and requires considerable
      skill and training. There have been prior studies establishing the efficacy of
      using a topical anesthetic in similar gynecologic procedures. We share our method
      of performing CVS, which aids in pain relief for the patient and concurrently
      aids the practitioner in executing this precise procedure. 

PMID- 24449742
TI  - Mitral valve dysplasia syndrome.

PMID- 24449743
TI  - Prenatal diagnosis of incomplete bladder duplication: sonographic features and
      perinatal management.

PMID- 24449744
TI  - Quantifying B-lines on lung sonography: insufficient evidence as an objective,
      constructive, and educational tool.

PMID- 24449745
TI  - Reply: To PMID 23269716.

PMID- 24449746
TI  - AIUM practice guideline for the performance of ultrasound examinations of the
      head and neck.

PMID- 24449748
TI  - Brain functional connectivity and morphology changes in medication-overuse
      headache: Clue for dependence-related processes?
AB  - BACKGROUND: Several imaging studies have identified localized anatomical and
      functional brain changes in medication-overuse headache (MOH). OBJECTIVE: The
      objective of this article is to evaluate whole-brain functional connectivity at
      rest together with voxel-based morphometry in MOH patients, in comparison with
      episodic migraine (EM) patients and healthy controls (HCs). METHODS: Anatomical
      MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17
      and 9, respectively), EM patients (n = 18 and 15, respectively) and HCs (n = 17
      and 17). SPM8 was used to analyze voxel-based morphometry and seed (left
      precuneus) to voxel connectivity data in the whole brain. RESULTS: Functional
      connectivity at rest was altered in MOH patients. Connectivity was decreased
      between precuneus and regions of the default-mode network (frontal and parietal
      cortices), but increased between precuneus and hippocampal/temporal areas. These
      functional modifications were not accompanied by significant gross morphological
      changes. Furthermore, connectivity between precuneus and frontal areas in MOH was
      negatively correlated with migraine duration and positively correlated with self
      evaluation of medication dependence. Gray matter volumes of frontal regions,
      precuneus and hippocampus were also negatively related to migraine duration.
      Functional connectivity within the default-mode network appeared to predict
      anxiety scores of MOH patients while gray matter volumes in this network
      predicted their depression scores. CONCLUSIONS: Our data suggest that MOH is
      associated with functional alterations within intrinsic brain networks rather
      than with macrostructural changes. They also support the view that dependence
      related processes might play a prominent role in its development and maintenance.

PMID- 24449749
TI  - Ecological succession and stochastic variation in the assembly of Arabidopsis
      thaliana phyllosphere communities.
AB  - Bacteria living on the aerial parts of plants (the phyllosphere) are globally
      abundant and ecologically significant communities and can have significant
      effects on their plant hosts. Despite their importance, little is known about the
      ecological processes that drive phyllosphere dynamics. Here, we describe the
      development of phyllosphere bacterial communities over time on the model plant
      Arabidopsis thaliana in a controlled greenhouse environment. We used a large
      number of replicate plants to identify repeatable dynamics in phyllosphere
      community assembly and reconstructed assembly history by measuring the
      composition of the airborne community immigrating to plant leaves. We used more
      than 260,000 sequences from the v5v6 hypervariable region of the 16S rRNA gene to
      characterize bacterial community structure on 32 plant and 21 air samples over 73
      days. We observed strong, reproducible successional dynamics: phyllosphere
      communities initially mirrored airborne communities and subsequently converged to
      a distinct community composition. While the presence or absence of particular
      taxa in the phyllosphere was conserved across replicates, suggesting strong
      selection for community composition, the relative abundance of these taxa was
      highly variable and related to the spatial association of individual plants. Our
      results suggest that stochastic events in early colonization, coupled with
      dispersal limitation, generated alternate trajectories of bacterial community
      assembly within the context of deterministic selection for community membership.
      IMPORTANCE: Commensal bacteria associated with plants help protect their hosts
      against infection and promote growth. Bacteria associated with plant leaves (the
      "phyllosphere") are highly abundant and diverse communities, but we have very
      limited information about their ecology. Here, we describe the formation of
      phyllosphere communities on the plant model organism Arabidopsis thaliana. We
      grew a large number of plants in a greenhouse and measured bacterial diversity in
      the phyllosphere throughout the Arabidopsis life cycle. We also measured the
      diversity of airborne microbes landing on leaves. Our findings show that plants
      develop distinctive phyllosphere bacterial communities drawn from low-abundance
      air populations, suggesting the plant environment is favorable for particular
      organisms and not others. However, we also found that the relative abundances of
      bacteria in the phyllosphere are determined primarily by the physical proximity
      of individual plants. This suggests that a mixture of selective and random forces
      shapes phyllosphere communities.

PMID- 24449750
TI  - Structural basis for the inhibition of the chromatin repressor BAHD1 by the
      bacterial nucleomodulin LntA.
AB  - The nucleus has emerged as a key target for nucleomodulins, a family of effectors
      produced by bacterial pathogens to control host transcription or other nuclear
      processes. The virulence factor LntA from Listeria monocytogenes stimulates
      interferon responses during infection by inhibiting BAHD1, a nuclear protein
      involved in gene silencing by promoting heterochromatin formation. So far,
      whether the interaction between LntA and BAHD1 is direct and sufficient for
      inhibiting BAHD1 activity is unknown. Here, we functionally characterized the
      molecular interface between the two proteins in vitro and in transfected or
      infected human cells. Based on the known tridimensional structure of LntA, we
      identified a dilysine motif (K180/K181) in the elbow region of LntA and a central
      proline-rich region in BAHD1 as crucial for the direct LntA-BAHD1 interaction. To
      better understand the role played by the dilysine motif in the functionality of
      LntA, we solved the crystal structure of a K180D/K181D mutant to a 2.2-A
      resolution. This mutant highlights a drastic redistribution of surface charges in
      the vicinity of a groove, which likely plays a role in nucleomodulin target
      recognition. Mutation of the strategic dilysine motif also abolished the
      recruitment of LntA to BAHD1-associated nuclear foci and impaired the LntA
      mediated stimulation of interferon responses upon infection. Last, the strict
      conservation of residues K180 and K181 in LntA sequences from 188 L.
      monocytogenes strains of different serotypes and origins further supports their
      functional importance. Together, these results provide structural and functional
      details about the mechanism of inhibition of an epigenetic factor by a bacterial
      nucleomodulin. IMPORTANCE: Pathogens have evolved various strategies to
      deregulate the expression of host defense genes during infection, such as
      targeting nuclear proteins. LntA, a secreted virulence factor from the bacterium
      Listeria monocytogenes, stimulates innate immune responses by inhibiting a
      chromatin-associated repressor, BAHD1. This study reveals the structural features
      of LntA required for BAHD1 inhibition. LntA interacts directly with a central
      domain of BAHD1 via a surface patch of conserved positive charges, located nearby
      a groove on the elbow region of LntA. By demonstrating that this patch is
      required for LntA function, we provide a better understanding of the molecular
      mechanism allowing a bacterial pathogen to control host chromatin compaction and
      gene expression.

PMID- 24449751
TI  - Systemic spread and propagation of a plant-pathogenic virus in European
      honeybees, Apis mellifera.
AB  - Emerging and reemerging diseases that result from pathogen host shifts are a
      threat to the health of humans and their domesticates. RNA viruses have extremely
      high mutation rates and thus represent a significant source of these infectious
      diseases. In the present study, we showed that a plant-pathogenic RNA virus,
      tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees,
      Apis mellifera, resulting in infections that were found throughout the entire
      body. Additionally, we showed that TRSV-infected individuals were continually
      present in some monitored colonies. While intracellular life cycle, species-level
      genetic variation, and pathogenesis of the virus in honeybee hosts remain to be
      determined, the increasing prevalence of TRSV in conjunction with other bee
      viruses from spring toward winter in infected colonies was associated with
      gradual decline of host populations and winter colony collapse, suggesting the
      negative impact of the virus on colony survival. Furthermore, we showed that TRSV
      was also found in ectoparasitic Varroa mites that feed on bee hemolymph, but in
      those instances the virus was restricted to the gastric cecum of Varroa mites,
      suggesting that Varroa mites may facilitate the spread of TRSV in bees but do not
      experience systemic invasion. Finally, our phylogenetic analysis revealed that
      TRSV isolates from bees, bee pollen, and Varroa mites clustered together, forming
      a monophyletic clade. The tree topology indicated that the TRSVs from arthropod
      hosts shared a common ancestor with those from plant hosts and subsequently
      evolved as a distinct lineage after transkingdom host alteration. This study
      represents a unique example of viruses with host ranges spanning both the plant
      and animal kingdoms. IMPORTANCE: Pathogen host shifts represent a major source of
      new infectious diseases. Here we provide evidence that a pollen-borne plant
      virus, tobacco ringspot virus (TRSV), also replicates in honeybees and that the
      virus systemically invades and replicates in different body parts. In addition,
      the virus was detected inside the body of parasitic Varroa mites, which consume
      bee hemolymph, suggesting that Varroa mites may play a role in facilitating the
      spread of the virus in bee colonies. This study represents the first evidence
      that honeybees exposed to virus-contaminated pollen could also be infected and
      raises awareness of potential risks of new viral disease emergence due to host
      shift events. About 5% of known plant viruses are pollen transmitted, and these
      are potential sources of future host-jumping viruses. The findings from this
      study showcase the need for increased surveillance for potential host-jumping
      events as an integrated part of insect pollinator management programs.

PMID- 24449752
TI  - New insights into dissemination and variation of the health care-associated
      pathogen Acinetobacter baumannii from genomic analysis.
AB  - Acinetobacter baumannii is a globally important nosocomial pathogen characterized
      by an increasing incidence of multidrug resistance. Routes of dissemination and
      gene flow among health care facilities are poorly resolved and are important for
      understanding the epidemiology of A. baumannii, minimizing disease transmission,
      and improving patient outcomes. We used whole-genome sequencing to assess
      diversity and genome dynamics in 49 isolates from one United States hospital
      system during one year from 2007 to 2008. Core single-nucleotide-variant-based
      phylogenetic analysis revealed multiple founder strains and multiple independent
      strains recovered from the same patient yet was insufficient to fully resolve
      strain relationships, where gene content and insertion sequence patterns added
      additional discriminatory power. Gene content comparisons illustrated extensive
      and redundant antibiotic resistance gene carriage and direct evidence of gene
      transfer, recombination, gene loss, and mutation. Evidence of barriers to gene
      flow among hospital components was not found, suggesting complex mixing of
      strains and a large reservoir of A. baumannii strains capable of colonizing
      patients. IMPORTANCE: Genome sequencing was used to characterize multidrug
      resistant Acinetobacter baumannii strains from one United States hospital system
      during a 1-year period to better understand how A. baumannii strains that cause
      infection are related to one another. Extensive variation in gene content was
      found, even among strains that were very closely related phylogenetically and
      epidemiologically. Several mechanisms contributed to this diversity, including
      transfer of mobile genetic elements, mobilization of insertion sequences,
      insertion sequence-mediated deletions, and genome-wide homologous recombination.
      Variation in gene content, however, lacked clear spatial or temporal patterns,
      suggesting a diverse pool of circulating strains with considerable interaction
      between strains and hospital locations. Widespread genetic variation among
      strains from the same hospital and even the same patient, particularly involving
      antibiotic resistance genes, reinforces the need for molecular diagnostic testing
      and genomic analysis to determine resistance profiles, rather than a reliance
      primarily on strain typing and antimicrobial resistance phenotypes for
      epidemiological studies.

PMID- 24449753
TI  - Twin-arginine translocation system in Helicobacter pylori: TatC, but not TatB, is
      essential for viability.
AB  - The twin-arginine translocation (Tat) system, needed to transport folded proteins
      across biological membranes, has not been characterized in the gastric pathogen
      Helicobacter pylori. Analysis of all H. pylori genome sequences available thus
      far reveals the presence of single copies of tatA, tatB, and tatC needed for the
      synthesis of a fully functional Tat system. Based on the presence of the twin
      arginine hallmark in their signal sequence, only four H. pylori proteins appear
      to be Tat dependent: hydrogenase (HydA), catalase-associated protein (KapA),
      biotin sulfoxide reductase (BisC), and the ubiquinol cytochrome oxidoreductase
      Rieske protein (FbcF). In the present study, targeted mutations were aimed at
      tatA, tatB, tatC, or queA (downstream gene control). While double homologous
      recombination mutations in tatB and queA were easily obtained, attempts at
      disrupting tatA proved unsuccessful, while deletion of tatC led to partial
      mutants following single homologous recombination, with cells retaining a
      chromosomal copy of tatC. Double homologous recombination tatC mutants were
      obtained only when a plasmid-borne, isopropyl-beta-d-thiogalactopyranoside (IPTG)
      inducible copy of tatC was introduced prior to transformation. These conditional
      tatC mutants could grow only in the presence of IPTG, suggesting that tatC is
      essential in H. pylori. tatB and tatC mutants had lower hydrogenase and catalase
      activities than the wild-type strain did, and the ability of tatC mutants to
      colonize mouse stomachs was severely affected compared to the wild type.
      Chromosomal complementation of tatC mutants restored hydrogenase and catalase
      activities to wild-type levels, and additional expression of tatC in wild-type
      cells resulted in elevated Tat-dependent enzyme activities. Unexpectedly, the tat
      strains had cell envelope defects. IMPORTANCE: This work reports the first
      characterization of the twin-arginine translocation (Tat) system in the gastric
      pathogen Helicobacter pylori. While tatB mutants were easily obtained, only
      single-crossover partial tatC mutants or conditional tatC mutants could be
      generated, indicating that tatC is essential in H. pylori, a surprising finding
      given the fact that only four proteins are predicted to be translocated by the
      Tat system in this bacterium. The levels of activity of hydrogenase and catalase,
      two of the predicted Tat-dependent enzymes, were affected in these mutants. In
      addition, all tat mutants displayed cell envelope defects, and tatC mutants were
      deficient in mouse colonization.

PMID- 24449754
TI  - Analysis of the mRNA targetome of microRNAs expressed by Marek's disease virus.
AB  - Marek's disease virus 1 (MDV-1), an oncogenic alpha-herpesvirus that induces T
      cell lymphomas in chickens, serves as model system to study transformation by
      lymphotropic herpesviruses. Like the oncogenic human gamma-herpesviruses Kaposi's
      sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), MDV-1 encodes
      several viral microRNAs (miRNAs). One MDV-1 miRNA, miR-M4, shares the same "seed"
      targeting sequence with both a KSHV miRNA, miR-K11, and cellular miR-155.
      Importantly, miR-M4 plays a critical role in T-cell transformation by MDV-1,
      while miR-K11 and cellular miR-155 are thought to play key roles in B-cell
      transformation by KSHV and EBV, respectively. Here, we present an analysis of the
      mRNAs targeted by viral miRNAs expressed in the chicken T-cell line MSB1, which
      is naturally coinfected with MDV-1 and the related nonpathogenic virus MDV-2. Our
      analysis identified >1,000 endogenous mRNAs targeted by miRNAs encoded by each
      virus, many of which are targeted by both MDV-1 and MDV-2 miRNAs. We present a
      functional analysis of an MDV-1 gene, RLORF8, targeted by four MDV-1 miRNAs and a
      cellular gene, encoding interleukin-18 (IL-18) and targeted by both MDV-1 and MDV
      2 miRNAs, and show that ectopic expression of either protein in a form resistant
      to miRNA inhibition results in inhibition of cell proliferation. Finally, we
      present a restricted list of 9 genes targeted by not only MDV-1 miR-M4 but also
      KSHV miR-K11 and human miR-155. Given the critical role played by miR-155 seed
      family members in lymphomagenesis in humans and chickens, these mRNA targets may
      contain genes whose inhibition plays a conserved role in herpesvirus
      transformation. IMPORTANCE: Herpesviruses cause lymphomas in both humans and
      chickens, and in both cases, evidence indicates that virally encoded miRNAs, or
      virally subverted cellular miRNAs, belonging to the miR-155 seed family, play a
      critical role in this process. However, because each miRNA regulates numerous
      cellular mRNAs species, it has been difficult to elucidate which miRNA targets
      are important. Given the evolutionary distance between chickens and humans and
      the observation that miR-155 is nevertheless highly conserved in both species, we
      reasoned that the identification of shared miR-155 targets might shed light on
      this process. Here, we present an analysis of the mRNAs targeted by miRNAs
      encoded by the oncogenic avian herpesvirus MDV-1 in transformed chicken T cells,
      including a short list of mRNAs that are also targeted by miR-155 seed family
      miRNAs in EBV- or KSHV-transformed human B cells, and present an initial
      functional analysis of some of these miRNA targets.

PMID- 24449755
TI  - Economic burden of foot and ankle surgery in the US Medicare population.
AB  - BACKGROUND: Musculoskeletal diseases affecting the foot and ankle are common and
      can result in debilitating pain and chronic disability. The purpose of this study
      was to estimate the economic burden associated with operative interventions
      targeting these afflictions in the Medicare population. METHODS: Procedure
      incidence was determined using data from Medicare Part B National Summary Data
      Files (for 2000-2011). Health care and productivity costs were estimated for each
      year using an incidence-based cost model, using demographic information from 10
      633 patient encounters at the University of Iowa Hospitals and Clinics over the
      period January 1, 2000, to December 31, 2010. RESULTS: The estimated economic
      burden of foot and ankle surgery in the Medicare population was $11 billion in
      2011, up 38.2% since 2000. Direct health care costs were responsible for only 11%
      of this total, while indirect productivity costs contributed the remainder.
      Procedures targeting the foot accounted for over two-thirds of total economic
      burden, or $7.6 billion. Treatments for fracture and dislocation contributed the
      most to overall economic burden (31.0% of total), followed by reconstructive
      procedures (30.7%) and amputations (13.3%). CONCLUSION: Even in an older
      population, considerable productivity losses are associated with foot and ankle
      surgery. An increasing share of the population older than 65 expects to be fit to
      work, making disability in older Americans more monetarily important. At the same
      time, trends in chronic disease mean that the incidence of foot and ankle
      problems is likely to increase in the Medicare population. LEVEL OF EVIDENCE:
      Level III, economic analysis.

PMID- 24449759
TI  - Fate of induced pluripotent stem cells following transplantation to murine
      seminiferous tubules.
AB  - Studies of human germ cell development are limited in large part by
      inaccessibility of germ cells during development. Moreover, although several
      studies have reported differentiation of mouse and human germ cells from
      pluripotent stem cells (PSCs) in vitro, differentiation of human germ cells from
      PSCs in vivo has not been reported. Here, we tested whether mRNA reprogramming in
      combination with xeno-transplantation may provide a viable system to probe the
      genetics of human germ cell development via use of induced pluripotent stem cells
      (iPSCs). For this purpose, we derived integration-free iPSCs via mRNA-based
      reprogramming with OCT3/4, SOX2, KLF4 and cMYC alone (OSKM) or in combination
      with the germ cell-specific mRNA, VASA (OSKMV). All iPSC lines met classic
      criteria of pluripotency. Moreover, global gene expression profiling did not
      distinguish large differences between undifferentiated OSKM and OSKMV iPSCs;
      however, some differences were observed in expression of pluripotency factors and
      germ cell-specific genes, and in epigenetic profiles and in vitro differentiation
      studies. In contrast, transplantation of undifferentiated iPSCs directly into the
      seminiferous tubules of germ cell-depleted immunodeficient mice revealed
      divergent fates of iPSCs produced with different factors. Transplantation
      resulted in morphologically and immunohistochemically recognizable germ cells in
      vivo, particularly in the case of OSKMV cells. Significantly, OSKMV cells also
      did not form tumors while OSKM cells that remained outside the seminiferous
      tubule proliferated extensively and formed tumors. Results indicate that mRNA
      reprogramming in combination with transplantation may contribute to tools for
      genetic analysis of human germ cell development.

PMID- 24449760
TI  - Effects of plasma-emulating light-emitting diode (LED) versus conventional LED on
      cytotoxic effects and polymerization capacity of orthodontic composites.
AB  - OBJECTIVES: The aim of this study was to evaluate, the cytotoxicity of
      orthodontic composites in vitro as a function of degree of conversion (DC) and
      the light curing units (LCU) employed on mouse fibroblast (L929). MATERIALS AND
      METHODS: Cured samples of the composites Light bond (Reliance Orthodontic
      Products, Itasca, Illinois, USA), Ortho bracket paste (Bisco, Schaumburg,
      Illinois, USA), Opal bond MV (OPAL, South Jordan, Utah, USA), and Transbond XT
      (3M, Monrovia, California, USA) were prepared. Polymerization was performed with
      two LCUs: VALO Ortho (Ultradent, South Jordan, Utah, USA) is a third-generation
      LCU and Elipar S10 (3M, USA) is a second-generation LCU. Four samples were
      immersed in cell culture medium to obtain composite extracts. After incubation of
      L929 cell cultures with the extracts obtained, cytotoxicity was determined using
      the methyl tetrazolium test. Fourier transform infrared spectroscopy (FTIR) was
      used to evaluate DC for five samples. A multivariate analysis of variance
      (ANOVA), two-way ANOVA, and Tukey's honestly significant difference test were
      utilized for statistical analyses. RESULTS: Cytotoxicity and DC of all tested
      composites (p < 0.001) and the interaction between composites and LCUs (p < 0.01)
      were significantly different. LCUs had no significant influence on the
      cytotoxicity and DC of composite materials (p > 0.05). The correlations between
      cell viability and DC were positive for three composites but statistically
      insignificant. CONCLUSION: Composites and LCUs must be matched with one another
      to result in satisfactory maximal biocompatibility and DC. Opal Bond plasma light
      emitting diode combination was a better choice for cell viability. Three
      composites showed a positive correlation between cytotoxicity and DC. Therefore
      high-intensity LCUs can be said to efficiently affect polymerization, and so,
      higher DC rates may achieve higher cell viability rates.

PMID- 24449761
TI  - The protective effects of endothelin-A receptor antagonist BQ-123 in
      pentylenetetrazole-induced seizure in rats.
AB  - Endothelin-1 has been shown to increase neuronal activity and glutaminergic
      synaptic transmission by endothelin-A receptors (ETAR) in the nucleus tractus
      solitarius neurons that play an important role in epileptic seizures. Therefore,
      BQ-123 as an ETAR antagonist might attenuate neuronal excitability and
      glutaminergic synaptic transmission. The main purpose of the present study is to
      investigate the protective effect of acute BQ-123 treatment against
      pentylenetetrazole (PTZ)-induced tonic-clonic seizures. Wistar albino rats were
      divided into three groups: control, PTZ, and PTZ + BQ-123 groups. BQ-123 (3
      mg/kg, intravenously) was administered for 15 min before injecting with PTZ (50
      mg/kg, intraperitoneally). We determined a delay resulting from BQ-123 in
      "duration of the seizure onset." "Number of rats with major seizure" also
      decreased according to scoring with video camera in PTZ + BQ-123 group. In BQ-123
      treated group, there were eight rats without a major seizure, but only one rat
      had a delayed major seizure. The brain tissue glutathione peroxidase activity was
      significantly decreased in the PTZ and PTZ + BQ-123 groups. According to the
      results of the control group, there was a significant increase in the protein
      carbonyl levels of the PTZ group and a significant increase in the nitric oxide
      levels of the PTZ + BQ-123 group. Histological examination showed an increase in
      the number of neuronal hyperchromatic nucleus especially in hippocampal gyrus
      dentatus region of BQ-123-treated group. We concluded that BQ-123 impeded the
      formation and spread of seizure to a great degree. The beneficial effects of BQ
      123 were comparatively supported with biochemical parameters and histological
      examinations. 

PMID- 24449762
TI  - Safe and fast proximal aortic control using an aortic balloon through direct
      graft puncture for the explantation of an abdominal endograft with suprarenal
      fixation.
AB  - The late removal of an abdominal aortic endograft is technically challenging and
      can be associated with significant blood loss, especially when a graft with
      active suprarenal fixation is involved. The main issue in safe explantation of
      the endograft is control of the aorta above the proximal fixation site. We report
      an adjunctive technique for the safe and fast proximal control of the suprarenal
      aorta using an aortic balloon. The endograft is directly punctured and an aortic
      balloon is deployed and inflated above the fixation site in the supracoeliac
      aorta. The time for supracoeliac control in our 2 patients was <5 min. This
      simple technique offers a safe and fast aortic control during the removal of the
      endograft, especially when active suprarenal fixation is used, avoiding the risks
      from a technically demanding dissection in a potentially inflammatory region. 

PMID- 24449763
TI  - Ligand binding shifts highly mobile retinoid X receptor to the chromatin-bound
      state in a coactivator-dependent manner, as revealed by single-cell imaging.
AB  - Retinoid X receptor (RXR) is a promiscuous nuclear receptor forming heterodimers
      with several other receptors, which activate different sets of genes. Upon
      agonist treatment, the occupancy of its genomic binding regions increased, but
      only a modest change in the number of sites was revealed by chromatin
      immunoprecipitation followed by sequencing, suggesting a rather static behavior.
      However, such genome-wide and biochemical approaches do not take into account the
      dynamic behavior of a transcription factor. Therefore, we characterized the
      nuclear dynamics of RXR during activation in single cells on the subsecond scale
      using live-cell imaging. By applying fluorescence recovery after photobleaching
      and fluorescence correlation spectroscopy (FCS), techniques with different
      temporal and spatial resolutions, a highly dynamic behavior could be uncovered
      which is best described by a two-state model (slow and fast) of receptor
      mobility. In the unliganded state, most RXRs belonged to the fast population,
      leaving ~ 15% for the slow, chromatin-bound fraction. Upon agonist treatment,
      this ratio increased to ~ 43% as a result of an immediate and reversible
      redistribution. Coactivator binding appears to be indispensable for
      redistribution and has a major contribution to chromatin association. A nuclear
      mobility map recorded by light sheet microscopy-FCS shows that the ligand-induced
      transition from the fast to the slow population occurs throughout the nucleus.
      Our results support a model in which RXR has a distinct, highly dynamic nuclear
      behavior and follows hit-and-run kinetics upon activation.

PMID- 24449764
TI  - S/T phosphorylation of DLL1 is required for full ligand activity in vitro but
      dispensable for DLL1 function in vivo during embryonic patterning and marginal
      zone B cell development.
AB  - Interaction of Notch receptors with Delta- and Serrate-type ligands is an
      evolutionarily conserved mechanism that mediates direct communication between
      adjacent cells and thereby regulates multiple developmental processes.
      Posttranslational modifications of both receptors and ligands are pivotal for
      normal Notch pathway function. We have identified by mass spectrometric analysis
      two serine and one threonine phosphorylation sites in the intracellular domain of
      the mouse Notch ligand DLL1. Phosphorylation requires cell membrane association
      of DLL1 and occurs sequentially at the two serine residues. Phosphorylation of
      one serine residue most likely by protein kinase B primes phosphorylation of the
      other serine. A DLL1 variant, in which all three identified phosphorylated
      serine/threonine residues are mutated to alanine and valine, was more stable than
      wild-type DLL1 but had reduced relative levels on the cell surface and was more
      effectively cleaved in the extracellular domain. In addition, the mutant variant
      activated Notch1 significantly less efficient than wild-type DLL1 in a coculture
      assay in vitro. Mice, however, whose endogenous DLL1 was replaced with the
      phosphorylation-deficient triple mutant developed normally, suggesting
      compensatory mechanisms under physiological conditions in vivo. 

PMID- 24449767
TI  - Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the
      United States from 2011 to 2013.
AB  - Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have
      become a public health concern in the United States. The A(H3N2)v viruses share
      the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but
      do not contain any known molecular markers associated with resistance to
      neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI)
      assay, the susceptibilities of recovered A(H3N2)v viruses (n=168) to FDA-approved
      (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs
      were assessed. All A(H3N2)v viruses tested, with the exception of a single virus
      strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to
      the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N
      and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold)
      and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins,
      S247P was shown to be responsible for the observed altered NAI susceptibility, in
      addition to an approximately 60% reduction in NA enzymatic activity. The S247P
      substitution has not been previously reported as a molecular marker of reduced
      susceptibility to the NAIs. Using cell culture assays, the investigational
      antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the
      replication of A(H3N2)v viruses, including the virus with the S247P substitution
      in the NA. This report demonstrates the importance of continuous monitoring of
      susceptibility of zoonotic influenza viruses to available and investigational
      antiviral drugs.

PMID- 24449765
TI  - Activation of p53 transcriptional activity by SMRT: a histone deacetylase 3
      independent function of a transcriptional corepressor.
AB  - The silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is
      an established histone deacetylase 3 (HDAC3)-dependent transcriptional
      corepressor. Microarray analyses of MCF-7 cells transfected with control or SMRT
      small interfering RNA revealed SMRT regulation of genes involved in DNA damage
      responses, and the levels of the DNA damage marker gammaH2AX as well as poly(ADP
      ribose) polymerase cleavage were elevated in SMRT-depleted cells treated with
      doxorubicin. A number of these genes are established p53 targets. SMRT knockdown
      decreased the activity of two p53-dependent reporter genes as well as the
      expression of p53 target genes, such as CDKN1A (which encodes p21). SMRT bound
      directly to p53 and was recruited to p53 binding sites within the p21 promoter.
      Depletion of GPS2 and TBL1, components of the SMRT corepressor complex, but not
      histone deacetylase 3 (HDAC3) decreased p21-luciferase activity. p53 bound to the
      SMRT deacetylase activation domain (DAD), which mediates HDAC3 binding and
      activation, and HDAC3 could attenuate p53 binding to the DAD region of SMRT.
      Moreover, an HDAC3 binding-deficient SMRT DAD mutant coactivated p53
      transcriptional activity. Collectively, these data highlight a biological role
      for SMRT in mediating DNA damage responses and suggest a model where p53 binding
      to the DAD limits HDAC3 interaction with this coregulator, thereby facilitating
      SMRT coactivation of p53-dependent gene expression. 

PMID- 24449766
TI  - The E3 ubiquitin ligase MARCH6 degrades squalene monooxygenase and affects 3
      hydroxy-3-methyl-glutaryl coenzyme A reductase and the cholesterol synthesis
      pathway.
AB  - The mevalonate pathway is used by cells to produce sterol and nonsterol
      metabolites and is subject to tight metabolic regulation. We recently reported
      that squalene monooxygenase (SM), an enzyme controlling a rate-limiting step in
      cholesterol biosynthesis, is subject to cholesterol-dependent proteasomal
      degradation. However, the E3-ubiquitin (E3) ligase mediating this effect was not
      established. Using a candidate approach, we identify the E3 ligase membrane
      associated RING finger 6 (MARCH6, also known as TEB4) as the ligase controlling
      degradation of SM. We find that MARCH6 and SM physically interact, and consistent
      with MARCH6 acting as an E3 ligase, its overexpression reduces SM abundance in a
      RING-dependent manner. Reciprocally, knockdown of MARCH6 increases the level of
      SM protein and prevents its cholesterol-regulated degradation. Additionally, this
      increases cell-associated SM activity but is unexpectedly accompanied by
      increased flux upstream of SM. Prompted by this observation, we found that
      knockdown of MARCH6 also controls the level of 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase (HMGCR) in hepatocytes and model cell lines. In conclusion,
      MARCH6 controls abundance of both SM and HMGCR, establishing it as a major
      regulator of flux through the cholesterol synthesis pathway. 

PMID- 24449768
TI  - Study of macrophage functions in murine J774 cells and human activated THP-1
      cells exposed to oritavancin, a lipoglycopeptide with high cellular accumulation.
AB  - Oritavancin, a lipoglycopeptide antibiotic in development, accumulates to high
      levels in the lysosomes of eukaryotic cells. We examined specific functions of
      macrophages (phagocytic capacity, lysosomal integrity, metabolic activity, and
      production of reactive oxygen species [ROS]) in correlation with the cellular
      accumulation of the drug, using J774 mouse macrophages and THP-1 human monocytes
      differentiated into macrophages using phorbol 12-myristate 13-acetate.
      Oritavancin did not affect Pseudomonas aeruginosa phagocytosis, lysosomal
      integrity, or metabolic activity in cells incubated for 3 h with extracellular
      concentrations ranging from 5 to 50 MUg/ml. At extracellular concentrations of
      >=25 MUg/ml, oritavancin reduced latex bead phagocytosis by approximately 50% and
      doubled ROS production in J774 macrophages only. This may result from the fact
      that the cellular accumulation of oritavancin was 15 times higher in J774 cells
      than in activated THP-1 cells at 3 h. Human pharmacokinetic studies estimate that
      the concentration of oritavancin in alveolar macrophages could reach
      approximately 560 MUg/ml after administration of a cumulative dose of 4 g, which
      is below the cellular concentration needed in the present study to impair latex
      bead phagocytosis (1,180 MUg/ml) or to stimulate ROS production (15,000 MUg/ml)
      by J774 cells. The data, therefore, suggest that, in spite of its substantial
      cellular accumulation, oritavancin is unlikely to markedly affect macrophage
      functions under the conditions of use investigated in current phase III trials (a
      single dose of 1,200 mg). 

PMID- 24449769
TI  - Detection of PER-2-producing Enterobacter cloacae in a Brazilian liver
      transplantation unit.

PMID- 24449770
TI  - Population pharmacokinetic assessment of the effect of food on piperaquine
      bioavailability in patients with uncomplicated malaria.
AB  - Previously published literature reports various impacts of food on the oral
      bioavailability of piperaquine. The aim of this study was to use a population
      modeling approach to investigate the impact of concomitant intake of a small
      amount of food on piperaquine pharmacokinetics. This was an open, randomized
      comparison of piperaquine pharmacokinetics when administered as a fixed oral
      formulation once daily for 3 days with (n=15) and without (n=15) concomitant food
      to patients with uncomplicated Plasmodium falciparum malaria in Thailand.
      Nonlinear mixed-effects modeling was used to characterize the pharmacokinetics of
      piperaquine and the influence of concomitant food intake. A modified Monte Carlo
      mapped power approach was applied to evaluate the relationship between
      statistical power and various degrees of covariate effect sizes of the given
      study design. Piperaquine population pharmacokinetics were described well in
      fasting and fed patients by a three-compartment distribution model with flexible
      absorption. The final model showed a 25% increase in relative bioavailability per
      dose occasion during recovery from malaria but demonstrated no clinical impact of
      concomitant intake of a low-fat meal. Body weight and age were both significant
      covariates in the final model. The novel power approach concluded that the study
      was adequately powered to detect a food effect of at least 35%. This modified
      Monte Carlo mapped power approach may be a useful tool for evaluating the power
      to detect true covariate effects in mixed-effects modeling and a given study
      design. A small amount of food does not affect piperaquine absorption
      significantly in acute malaria.

PMID- 24449771
TI  - Selective target inactivation rather than global metabolic dormancy causes
      antibiotic tolerance in uropathogens.
AB  - Persister cells represent a multidrug-tolerant (MDT), physiologically distinct
      subpopulation of bacteria. The ability of these organisms to survive lethal
      antibiotic doses raises concern over their potential role in chronic disease,
      such as recurrent urinary tract infection (RUTI). Persistence is believed to be
      conveyed through global metabolic dormancy, which yields organisms unresponsive
      to external stimuli. However, recent studies have contested this stance. Here,
      various antibiotics that target different cellular processes were used to dissect
      the activity of transcription, translation, and peptidoglycan turnover in
      persister cells. Differential susceptibility patterns were found in type I and
      type II persisters, and responses differed between Staphylococcus saprophyticus
      and Escherichia coli uropathogens. Further, SOS-deficient strains were sensitized
      to ciprofloxacin, suggesting DNA gyrase activity in persisters and indicating the
      importance of active DNA repair systems for ciprofloxacin tolerance. These
      results indicate that global dormancy per se cannot sufficiently account for
      antibiotic tolerance. Rather, the activity of individual cellular processes
      dictates multidrug tolerance in an antibiotic-specific fashion. Furthermore, the
      susceptibility patterns of persisters depended on their mechanisms of onset, with
      subinhibitory antibiotic pretreatments selectively shutting down cognate targets
      and increasing the persister fraction against the same agent. Interestingly,
      antibiotics targeting transcription and translation enhanced persistence against
      multiple agents indirectly related to these processes. Conducting these assays
      with uropathogenic E. coli isolated from RUTI patients revealed an enriched
      persister fraction compared to organisms cleared with standard antibiotic
      therapy. This finding suggests that persister traits are either selected for
      during prolonged antibiotic treatment or initially contribute to therapy failure.

PMID- 24449772
TI  - Detection of NDM-1-, CTX-M-15-, and qnrB4-producing Enterobacter hormaechei
      isolates in Brazil.

PMID- 24449773
TI  - ICESp1116, the genetic element responsible for erm(B)-mediated, inducible
      erythromycin resistance in Streptococcus pyogenes, belongs to the TnGBS family of
      integrative and conjugative elements.

PMID- 24449774
TI  - Enterobacteriaceae with extended-spectrum- and pAmpC-type beta-lactamase-encoding
      genes isolated from freshwater fish from two lakes in Switzerland.

PMID- 24449775
TI  - Tripoli metallo-beta-lactamase-1 (TMB-1)-producing Acinetobacter spp. with
      decreased resistance to imipenem in Japan.

PMID- 24449776
TI  - Preclinical safety evaluation of intravenously administered SAL200 containing the
      recombinant phage endolysin SAL-1 as a pharmaceutical ingredient.
AB  - Phage endolysins have received increasing attention as potent antibacterial
      agents. However, although safety evaluation is a prerequisite for the drug
      development process, a good laboratory practice (GLP)-compliant safety evaluation
      has not been reported for phage endolysins. A safety evaluation of intravenously
      administered SAL200 (containing phage endolysin SAL-1) was conducted according to
      GLP standards. No animals died in any of the safety evaluation studies. In
      general toxicity studies, intravenously administered SAL200 showed no sign of
      toxicity in rodent single- and repeated-dose toxicity studies. In the dog
      repeated-dose toxicity test, there were no abnormal findings, with the exception
      of transient abnormal clinical signs that were observed in some dogs when daily
      injection of SAL200 was continued for more than 1 week. In safety pharmacology
      studies, there were also no signs of toxicity in the central nervous and
      respiratory system function tests. In the cardiovascular function test, there
      were no abnormal findings in all tested dogs after the first and second
      administrations, but transient abnormalities were observed after the third and
      fourth administrations (2 or 3 weeks after the initial administration). All
      abnormal findings observed in these safety evaluation studies were slight to
      mild, were apparent only transiently after injection, and resolved quickly. The
      safety evaluation results for SAL200 support the implementation of an exploratory
      phase I clinical trial and underscore the potential of SAL200 as a new drug. We
      have designed an appropriate phase I clinical trial based on the results of this
      study. 

PMID- 24449777
TI  - Sesquiterpene lactone in nanostructured parenteral dosage form is efficacious in
      experimental Chagas disease.
AB  - The drugs available for Chagas disease treatment are toxic and ineffective. We
      studied the in vivo activity of a new drug, lychnopholide (LYC). LYC was loaded
      in nanocapsules (NC), and its effects were compared to free LYC and benznidazole
      against Trypanosoma cruzi. Infected mice were treated in the acute phase at 2.0
      mg/kg/day with free LYC, LYC-poly-epsilon-caprolactone NC (LYC-PCL), and LYC
      poly(lactic acid)-co-polyethylene glycol NC (LYC-PLA-PEG) or at 50 mg/kg/day with
      benznidazole solution by the intravenous route. Animals infected with the CL
      strain, treated 24 h after infection for 10 days, evaluated by hemoculture, PCR,
      and enzyme-linked immunosorbent assay exhibited a 50% parasitological cure when
      treated with LYC-PCL NC and 100% cure when treated with benznidazole, but 100% of
      the animals treated during the prepatent period for 20 days with these
      formulations or LYC-PLA-PEG NC were cured. In animals with the Y strain treated
      24 h after infection for 10 days, only mice treated by LYC-PCL NC were cured, but
      animals treated in the prepatent period for 20 days exhibited 100, 75, and 62.5%
      cure when treated with LYC-PLA-PEG NC, benznidazole, and LYC-PCL NC,
      respectively. Free LYC reduced the parasitemia and improved mice survival, but no
      mice were cured. LYC-loaded NC showed higher cure rates, reduced parasitemia, and
      increased survival when used in doses 2five times lower than those used for
      benznidazole. This study confirms that LYC is a potential new treatment for
      Chagas disease. Furthermore, the long-circulating property of PLA-PEG NC and its
      ability to improve LYC efficacy showed that this formulation is more effective in
      reaching the parasite in vivo. 

PMID- 24449778
TI  - The antituberculosis antibiotic capreomycin inhibits protein synthesis by
      disrupting interaction between ribosomal proteins L12 and L10.
AB  - Capreomycin is a second-line drug for multiple-drug-resistant tuberculosis (TB).
      However, with increased use in clinics, the therapeutic efficiency of capreomycin
      is decreasing. To better understand TB resistance to capreomycin, we have done
      research to identify the molecular target of capreomycin. Mycobacterium
      tuberculosis ribosomal proteins L12 and L10 interact with each other and
      constitute the stalk of the 50S ribosomal subunit, which recruits initiation and
      elongation factors during translation. Hence, the L12-L10 interaction is
      considered to be essential for ribosomal function and protein synthesis. Here we
      provide evidence showing that capreomycin inhibits the L12-L10 interaction by
      using an established L12-L10 interaction assay. Overexpression of L12 and/or L10
      in M. smegmatis, a species close to M. tuberculosis, increases the MIC of
      capreomycin. Moreover, both elongation factor G-dependent GTPase activity and
      ribosome-mediated protein synthesis are inhibited by capreomycin. When protein
      synthesis was blocked with thiostrepton, however, the bactericidal activity of
      capreomycin was restrained. All of these results suggest that capreomycin seems
      to inhibit TB by interrupting the L12-L10 interaction. This finding might provide
      novel clues for anti-TB drug discovery. 

PMID- 24449779
TI  - Silymarin reduces profibrogenic cytokines and reverses hepatic fibrosis in
      chronic murine schistosomiasis.
AB  - In chronic schistosomiasis, hepatic fibrosis is linked to the portal hypertension
      that causes morbidity in Schistosoma mansoni infection. Silymarin (SIL) is a
      hepatoprotective and antioxidant medicament largely prescribed against liver
      diseases that has previously been shown to prevent fibrosis during acute murine
      schistosomiasis. Here we employed silymarin to try to reverse established hepatic
      fibrosis in chronic schistosomiasis. Silymarin or vehicle was administered to
      BALB/c mice every 48 h, starting on the 40th (80 days of treatment), 70th (50
      days), or 110th (10 days) day postinfection (dpi). All mice were sacrificed and
      analyzed at 120 dpi. Treatment with silymarin reduced liver weight and granuloma
      sizes, reduced the increase in alanine aminotransferase and aspartate
      aminotransferase levels, and reduced the established hepatic fibrosis (assessed
      by hydroxyproline contents and picrosirius staining). Treatment with silymarin
      also reduced the levels of interleukin-13 (IL-13) in serum and increased the
      gamma interferon (IFN-gamma)/IL-13 ratio. There was a linear correlation between
      IL-13 levels in serum and hydroxyproline hepatic content in both infected
      untreated and SIL-treated mice, with decreased IL-13 levels corresponding to
      decreased hydroxyproline hepatic contents. Treatment with either SIL or N
      acetylcysteine reduced both proliferation of fibroblast cell lines and basal/IL
      13-induced production of collagen I, indicating that besides inhibiting IL-13
      production during infection, SIL antioxidant properties most likely contribute to
      inhibition of collagen production downstream of IL-13. These results show that
      silymarin interferes with fibrogenic cytokines, reduces established fibrosis, and
      inhibits downstream effects of IL-13 on fibrogenesis, indicating the drug as a
      safe and cheap treatment to liver fibrotic disease in schistosomiasis. 

PMID- 24449780
TI  - Post-beta-lactamase-inhibitor effect of tazobactam in combination with
      ceftolozane on extended-spectrum-beta-lactamase-producing strains.
AB  - The post-beta-lactamase-inhibitor effect (PBLIE) of tazobactam combined with
      ceftolozane was evaluated by time-kill assays on two clinical Escherichia coli
      strains producing CTX-M-15 with or without TEM-1. The organisms were exposed (2
      h) to 4 MUg/ml/4 MUg/ml of ceftolozane-tazobactam (4* MIC), 4 MUg/ml of
      ceftolozane, and medium containing no drug, washed, and resuspended in medium
      alone or medium containing ceftolozane-tazobactam or ceftolozane. The PBLIE was
      determined as 1.3 to 2.1 h, and a postantibiotic effect was measured as 0.8 to
      0.9 h. 

PMID- 24449781
TI  - 2,3-dihydroxybenzoic acid-containing nanofiber wound dressings inhibit biofilm
      formation by Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa forms biofilms in wounds, which often leads to chronic
      infections that are difficult to treat with antibiotics. Free iron enhances
      biofilm formation, delays wound healing, and may even be responsible for
      persistent inflammation, increased connective tissue destruction, and lipid
      peroxidation. Exposure of P. aeruginosa Xen 5 to the iron chelator 2,3
      dihydroxybenzoic acid (DHBA), electrospun into a nanofiber blend of poly(d,l
      lactide) (PDLLA) and poly(ethylene oxide) (PEO), referred to as DF, for 8 h
      decreased biofilm formation by approximately 75%. This was shown by a drastic
      decline in cell numbers, from 7.1 log10 CFU/ml to 4.8 log10 CFU/ml when biofilms
      were exposed to DF in the presence of 2.0 mM FeCl3 6H2O. A similar decline in
      cell numbers was recorded in the presence of 3.0 mM FeCl3 6H2O and DF. The cells
      were more mobile in the presence of DHBA, supporting the observation of less
      biofilm formation at lower iron concentrations. DHBA at MIC levels (1.5 mg/ml)
      inhibited the growth of strain Xen 5 for at least 24 h. Our findings indicate
      that DHBA electrospun into nanofibers inhibits cell growth for at least 4 h,
      which is equivalent to the time required for all DHBA to diffuse from DF. This is
      the first indication that DF can be developed into a wound dressing to treat
      topical infections caused by P. aeruginosa. 

PMID- 24449783
TI  - Chaperone function and mechanism of small heat-shock proteins.
AB  - Small heat-shock proteins (sHSPs) are ubiquitous ATP-independent molecular
      chaperones that play crucial roles in protein quality control in cells. They are
      able to prevent the aggregation and/or inactivation of various non-native
      substrate proteins and assist the refolding of these substrates independently or
      under the help of other ATP-dependent chaperones. Substrate recognition and
      binding by sHSPs are essential for their chaperone functions. This review focuses
      on what natural substrate proteins an sHSP protects and how it binds the
      substrates in cells under fluctuating conditions. It appears that sHSPs of
      prokaryotes, although being able to bind a wide range of cellular proteins,
      preferentially protect certain classes of functional proteins, such as
      translation-related proteins and metabolic enzymes, which may well explain why
      they could increase the resistance of host cells against various stresses.
      Mechanistically, the sHSPs of prokaryotes appear to possess numerous multi-type
      substrate-binding residues and are able to hierarchically activate these residues
      in a temperature-dependent manner, and thus act as temperature-regulated
      chaperones. The mechanism of hierarchical activation of substrate-binding
      residues is also discussed regarding its implication for eukaryotic sHSPs. 

PMID- 24449784
TI  - Role of erbB3 receptors in cancer therapeutic resistance.
AB  - ErbB3 receptors are unique members of the erbB receptor tyrosine kinases (RTKs),
      which are often aberrantly expressed and/or activated in human cancers. Unlike
      other members in the family, erbB3 lacks or has impaired kinase activity. To
      transduce cell signaling, erbB3 has to interact with other RTKs and to be
      phosphorylated by its interactive partners, of those, erbB2 is the most important
      one. ErbB3 is frequently co-expressed with other RTKs in cancer cells to activate
      oncogenic signaling, such as phosphoinositide-3-kinase/protein kinase B (Akt)
      pathway, mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein
      kinase (MAPK) pathway, Janus kinase (Jak)/signal transducer and activator of
      transcription (Stat) pathway, etc. and thereby promote tumorigenesis. Numerous
      studies have demonstrated that activation of erbB3 signaling plays an important
      role in the progression of a variety of tumor types, such as erbB2-overexpressing
      breast cancer, castration-resistant prostate cancer, platinum
      refractory/resistant ovarian cancer, epidermal growth factor receptor TKI
      resistant non-small-cell lung cancer, and others. Basic research on the
      underlying mechanisms implicated the functions of erbB3 as a major cause of
      treatment failure in cancer therapy. Thus, concomitant inhibition of erbB3 is
      thought to be required to overcome the resistance and to effectively treat human
      cancers. This review focuses on the latest advances in our understanding of erbB3
      initiated signaling in the development of resistance to cancer treatments.

PMID- 24449785
TI  - The biology of melanocyte and melanocyte stem cell.
AB  - The melanocyte stem cells of the hair follicle provide an attractive system for
      the study of the stem cells. Successful regeneration of a functional organ relies
      on the organized and timely orchestration of molecular events among distinct
      stem/progenitor cell populations. The stem cells are regulated by communication
      with their specialized microenvironment known as the niche. Despite remarkable
      progress in understanding stem cell-intrinsic behavior, the molecular nature of
      the extrinsic factors provided to the stem cells by the niche microenvironment
      remains poorly understood. In this regard, the bulge niche of the mammalian hair
      follicle offers an excellent model for study. It holds two resident populations
      of SCs: epidermal stem cells and melanocyte stem cells. While their behavior is
      tightly coordinated, very little of the crosstalk involved is known. This review
      summarized the recent development in trying to understand the regulation of
      melanocyte and melanocyte stem cells. A better understanding of the normal
      regulation and behaviors of the melanocytes and the melanocyte stem cells will
      help to improve the clinical applications in regenerative medicine, cancer
      therapy, and aging. 

PMID- 24449786
TI  - Chryseobacterium gallinarum sp. nov., isolated from a chicken, and
      Chryseobacterium contaminans sp. nov., isolated as a contaminant from a
      rhizosphere sample.
AB  - Two yellow-pigmented bacterial strains (100(T) and C26(T)), showing 98.4 % 16S
      rRNA gene sequence similarity to each other and isolated from a chicken in
      Germany and as a contaminant from an agar plate of a rhizosphere sample in
      Alabama, were studied by using a polyphasic taxonomic approach. Cells of both
      isolates were rod-shaped and stained Gram-negative. A comparison of the 16S rRNA
      gene sequences of the two organisms with the sequences of the type strains of the
      most closely related species of the genus Chryseobacterium showed the highest
      sequence similarities of strains 100(T) and C26(T) to the type strains of
      Chryseobacterium joostei (respectively 97.5 and 98.2 %), C. viscerum (96.6, 97.8
      %), C. gleum (97.1, 97.7 %), C. arthrosphaerae (97.3%, 97.7 %), C. indologenes
      (97.2, 97.7 %), C. tructae (96.6, 97.6 %), C. jejuense (97.0, 97.6 %) and C.
      oncorhynchi (96.3, 97.5 %); 16S rRNA gene sequence similarities to members of all
      other species of the genus Chryseobacterium were below 97.5 %. The fatty acid
      profiles of both strains consisted of the major fatty acids iso-C15 : 0, summed
      feature 3 (iso-C15 : 0 2-OH and/or C16 : 1omega7c), iso-C17 : 1omega9c and iso
      C17 : 0 3-OH, but also showed slight differences (absence or presence of C16 : 0
      3-OH and iso-C15 : 1 F). DNA-DNA hybridizations between the two strains and
      between the novel strains and the type strains of C. joostei, C. indologenes, C.
      jejuense, C. tructae and C. viscerum resulted in relatedness values clearly below
      70 %. These DNA-DNA hybridization results and the differentiating biochemical and
      chemotaxonomic properties showed that both strains 100(T) and C26(T) represent
      novel species, for which the names Chryseobacterium gallinarum sp. nov. (type
      strain 100(T) = LMG 27808(T) = CCM 8493(T)) and Chryseobacterium contaminans sp.
      nov. (type strain C26(T) = LMG 27810(T) = CCM 8492(T)) are proposed. 

PMID- 24449787
TI  - Rhizobium rhizoryzae sp. nov., isolated from rice roots.
AB  - Two strains (J3-AN59(T) and J3-N84) of Gram-stain-negative, aerobic and rod
      shaped bacteria were isolated from the roots of fresh rice plants. The 16S rRNA
      gene sequence similarity results showed that the similarity between strains J3
      AN59(T) and J3-N84 was 100 %. Both strains were phylogenetically related to
      members of the genus Rhizobium, and they were most closely related to Rhizobium
      tarimense ACCC 06128(T) (97.43 %). Similarities in the sequences of housekeeping
      genes between strains J3-AN59(T) and J3-N84 and those of recognized species of
      the genus Rhizobium were less than 90 %. The polar lipid profiles of both strains
      were predominantly composed of phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine and an unknown aminophospholipid.
      The major cellular fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 :
      1omega6c) and C16 : 0. The DNA G+C contents of J3-AN59(T) and J3-N84 were 55.7
      and 57.1 mol%, respectively. The DNA-DNA relatedness value between J3-AN59(T) and
      J3-N84 was 89 %, and strain J3-AN59(T) showed 9 % DNA-DNA relatedness to R.
      tarimense ACCC 06128(T), the most closely related strain. Based on this evidence,
      we found that J3-AN59(T) and J3-N84 represent a novel species in the genus
      Rhizobium and we propose the name Rhizobium rhizoryzae sp. nov. The type strain
      is J3-AN59(T) ( = ACCC 05916(T) = KCTC 23652(T)). 

PMID- 24449788
TI  - Phaeobacter aquaemixtae sp. nov., isolated from the junction between the ocean
      and a freshwater spring.
AB  - A Gram-reaction-negative, aerobic, non-spore-forming, non-motile and rod-shaped
      or ovoid bacterial strain, designated SSK6-1(T), was isolated from the zone where
      the ocean and a freshwater spring meet at Jeju island, South Korea. Strain SSK6
      1(T) grew optimally at 30  degrees C, at pH 7.0-7.5 and in the presence of 2.0 %
      (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that
      strain SSK6-1(T) clustered with Phaeobacter daeponensis TF-218(T) and Phaeobacter
      caeruleus LMG 24369(T), exhibiting sequence similarities of 98.6 and 98.3 %,
      respectively. The novel strain exhibited sequence similarities of 94.6-97.8 % to
      the type strains of other recognized species of the genera Phaeobacter and
      Leisingera. Strain SSK6-1(T) contained Q-10 as the predominant ubiquinone and C18
      : 1omega7c and 11-methyl C18 : 1omega7c as the major fatty acids. The major polar
      lipids of strain SSK6-1(T) were phosphatidylcholine, phosphatidylglycerol,
      phosphatidylethanolamine, one unidentified aminolipid and one unidentified lipid.
      The DNA G+C content of strain SSK6-1(T) was 64.6 mol% and its DNA-DNA relatedness
      values with P. daeponensis TF-218(T) and P. caeruleus were 21 and 25 %,
      respectively. The differential phenotypic properties, together with phylogenetic
      and genetic distinctiveness, revealed that strain SSK6-1(T) is separate from
      recognized Phaeobacter species. On the basis of the data presented, strain SSK6
      1(T) is considered to represent a novel species of the genus Phaeobacter, for
      which the name Phaeobacter aquaemixtae sp. nov. is proposed. The type strain is
      SSK6-1(T) ( = KCTC 32538(T) = CECT 8399(T)). 

PMID- 24449789
TI  - Sphingomonas daechungensis sp. nov., isolated from sediment of a eutrophic
      reservoir.
AB  - Strain CH15-11(T), isolated from a sediment sample taken from Daechung Reservoir,
      South Korea, during the late-blooming period of cyanobacteria, was found to be a
      Gram-stain-negative, non-motile, non-spore-forming, rod-shaped and aerobic
      bacterium. Strain CH15-11(T) grew optimally at pH 7 and 28-30  degrees C.
      According to a phylogenetic tree based on 16S rRNA gene sequences, strain CH15
      11(T) belonged to the genus Sphingomonas and clustered with Sphingomonas
      sediminicola Dae 20(T), with which it shared the highest 16S rRNA gene sequence
      similarity (97.6 %). Chemotaxonomic analysis showed that strain CH15-11(T) had
      characteristics typical of members of the genus Sphingomonas, such as the
      presence of sphingoglycolipid, ubiquinone Q-10 and sym-homospermidine. Plus,
      strain CH15-11(T) included summed feature 8 (C18 : 1omega7c and/or C18 :
      1omega6c) and C16 : 0 as the major fatty acids. The genomic DNA G+C content was
      65.6 mol%. Sequence data showed that strain CH15-11(T) was most closely related
      to Sphingomonas sediminicola Dae 20(T) (97.6 %), Sphingomonas ginsengisoli Gsoil
      634(T) (97.2 %) and
      http://www.genebank.go.kr/eng/microbe/microbe_search_view.jsp?sStrainsn=4602Sphin
      omonas jaspi TDMA-16(T) (97.0 %). However, the DNA-DNA relatedness values between
      strain CH15-11(T) and the most closely related type strains were within a range
      of 35-59 %. Thus, based on the phylogenetic, phenotypic and genetic data, strain
      CH15-11(T) was classified as a member of the genus Sphingomonas as a
      representative of a novel species, for which the name Sphingomonas daechungensis
      sp. nov. is proposed. The type strain is CH15-11(T) ( = KCTC 23718(T) = JCM
      17887(T)). 

PMID- 24449790
TI  - Paenibacillus darwinianus sp. nov., isolated from gamma-irradiated Antarctic
      soil.
AB  - A novel bacterium, strain Br(T), was isolated from gamma-irradiated soils of the
      Britannia drift, Lake Wellman Region, Antarctica. This isolate was rod-shaped,
      endospore forming, Gram-stain-variable, catalase-positive, oxidase-negative and
      strictly aerobic. Cells possessed a monotrichous flagellum. Optimal growth was
      observed at 18  degrees C, pH 7.0 in PYGV or R2A broth. The major cellular fatty
      acid was anteiso-C15 : 0 (63.4 %). Primary identified lipids included
      phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. Total
      phospholipid was 60 % (w/w) of the total lipid extract. MK-7 was the dominant
      isoprenoid quinone. The genomic DNA G+C content was 55.6 mol%. Based on 16S rRNA
      gene sequence similarity, strain Br(T) clusters within the genus Paenibacillus
      with similarity values ranging from 93.9 to 95.1 %. Phylogenetic analyses by
      maximum-likelihood, maximum-parsimony and neighbour-joining methods revealed that
      strain Br(T) clusters with Paenibacillus daejeonensis (AF290916), Paenibacillus
      tarimensis (EF125184) and Paenibacillus pinihumi (GQ423057), albeit with weak
      bootstrap support. On the basis of phenotypic, chemotaxonomic and phylogenetic
      characteristics, we propose that strain Br(T) represents a novel species,
      Paenibacillus darwinianus sp. nov. The type strain is Br(T) ( = DSM 27245(T) =
      ICMP 19912(T)). 

PMID- 24449791
TI  - Mumia flava gen. nov., sp. nov., an actinobacterium of the family
      Nocardioidaceae.
AB  - A novel actinobacterial strain, designated MUSC 201T, was isolated from a
      mangrove soil collected from Kuantan, the capital city of Pahang State in
      Malaysia. The taxonomic status of this strain was determined using a polyphasic
      approach. Comparative 16S rRNA gene sequence analysis revealed that strain MUSC
      201T represented a novel lineage within the class Actinobacteria. Strain MUSC
      201T formed a distinct clade in the family Nocardioidaceae and was most closely
      related to the members of the genera Nocardioides (16S rRNA gene sequence
      similarity, 91.9-95.1%), Aeromicrobium (92.7-94.6%), Marmoricola (92.5-93.1%) and
      Kribbella (91.5-92.4%). The cells of this strain were irregular coccoid to short
      rod shaped. The peptidoglycan contained ll-diaminopimelic acid as diagnostic
      diamino acid and the peptidoglycan type was A3gamma. The peptidoglycan cell wall
      contained ll-diaminopimelic acid, glycine, glutamic acid and alanine in a molar
      ratio of 1.5:0.9:1.0:1.5. The cell-wall sugars were galactose and rhamnose. The
      predominant menaquinone was MK-9(H4). The polar lipids consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipid, glycolipid and
      four unknown phospholipids. The major cellular fatty acids were C18:1omega9c
      (30.8%), C16:0 (24.1%), and 10-methyl C18:0 (13.9%). The DNA G+C content was
      72.0+/-0.1 mol%. On the basis of phylogenetic and phenotypic differences from
      members of the genera of the family Nocardioidaceae, a novel genus and species,
      Mumia flava gen. nov., sp. nov. are proposed. The type strain of Mumia flava is
      MUSC 201T (=DSM 27763T=MCCC 1A00646T=NBRC 109973T).

PMID- 24449792
TI  - Methanobacterium paludis sp. nov. and a novel strain of Methanobacterium lacus
      isolated from northern peatlands.
AB  - Two mesophilic, hydrogenotrophic methanogens, designated strains SWAN1T and AL
      21, were isolated from two contrasting peatlands: a near circumneutral temperate
      minerotrophic fen in New York State, USA, and an acidic boreal poor fen site in
      Alaska, USA, respectively. Cells of the two strains were rod-shaped, non-motile,
      stained Gram-negative and resisted lysis with 0.1% SDS. Cell size was 0.6*1.5-2.8
      um for strain SWAN1T and 0.45-0.85*1.5-35 um for strain AL-21. The strains used
      H2/CO2 but not formate or other substrates for methanogenesis, grew optimally
      around 32-37  degrees C, and their growth spanned through a slightly low to
      neutral pH range (4.7-7.1). Strain AL-21 grew optimally closer to neutrality at
      pH 6.2, whereas strain SWAN1T showed a lower optimal pH at 5.4-5.7. The two
      strains were sensitive to NaCl with a maximal tolerance at 160 mM for strain
      SWAN1T and 50 mM for strain AL-21. Na2S was toxic at very low concentrations
      (0.01-0.8 mM), resulting in growth inhibition above these values. The DNA G+C
      content of the genomes was 35.7 mol% for strain SWAN1T and 35.8 mol% for strain
      AL-21. Phylogenetic analysis of the 16S rRNA gene sequences showed that the
      strains are members of the genus Methanobacterium. Strain SWAN1T shared 94-97%
      similarity with the type strains of recognized species of the genus
      Methanobacterium, whereas strain AL-21 shared 99% similarity with
      Methanobacterium lacus 17A1T. On the basis of phenotypic, genomic and
      phylogenetic characteristics, strain SWAN1T (=DSM 25820T=JCM 18151T) is proposed
      as the type strain of a novel species, Methanobacterium paludis sp. nov., while
      strain AL-21 is proposed as a second strain of Methanobacterium lacus.

PMID- 24449793
TI  - Sneathiella chungangensis sp. nov., isolated from a marine sand, and emended
      description of the genus Sneathiella.
AB  - A Gram-stain-negative, non-spore-forming, motile, strictly aerobic bacterial
      strain, designated CAU 1294T, was isolated from a sand sample and its taxonomic
      position was investigated using a polyphasic approach. The strain grew optimally
      at pH 6.5 and 30  degrees C and in the presence of 2% (w/v) NaCl. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain CAU 1294T formed a
      lineage with member of the genus Sneathiella and exhibited similarity to
      Sneathiella glossodoripedis MKT133T (96.3% similarity) and Sneathiella chinensis
      LMG 23452T (95.1% similarity). Strain CAU 1294T contained Q-10 as the predominant
      respiratory quinone. C18:1omega7c, C16:0 and cyclo-C19:0omega8c were the major
      cellular fatty acids. The polar lipids were composed of phosphatidylethanolamine,
      phosphatidylmethylethanolamine and two unidentified phospholipids. The DNA G+C
      content was 56.6 mol%. On the basis of these results, strain CAU 1294T is
      considered to represent a novel species of the genus Sneathiella, for which the
      name Sneathiella chungangensis is proposed. The type strain is CAU 1294T (=KCTC
      32476T=CECT 8513T). An emended description of the genus Sneathiella is also
      proposed.

PMID- 24449795
TI  - Fibrous incudostapedial joint in congenital aural atresia.
AB  - OBJECTIVES: (1) Determine the prevalence of a non-bony or fibrous incudostapedial
      (IS) joint in the setting of congenital aural atresia. (2) Assess this anomaly's
      impact on surgical management and associated hearing outcomes. STUDY DESIGN:
      Retrospective chart review. SETTING: Subspecialty private practice. SUBJECTS AND
      METHODS: Operative reports and audiometric data of patients who underwent
      congenital aural atresia repair by a single surgeon from 2007 to 2011 were
      reviewed for operative anatomic findings and audiometric outcomes. RESULTS: Two
      hundred twenty-eight operations on 206 ears were performed. Median age was 5
      years old. Fifty-five (26.7%) of these ears had a fibrous IS joint. The severity
      of this anomaly was graded as mild in 23 ears, moderate in 20 ears, and severe in
      12 ears. Mean postoperative pure tone air conduction (PTA2) in the severely
      fibrous group was 51 compared to 46 in the moderate group (P = .03) and 41 in the
      mild group (P = .006). Patients with a fibrous IS joint who underwent successful
      ossicular chain reconstruction (OCR) had a mean postoperative PTA2 of 30, which
      was a significantly better outcome than in patients with moderately or severely
      fibrous IS joints who did not have OCR (P < .05). CONCLUSION: A fibrous IS joint
      was seen in 27% of patients undergoing repair of congenital aural atresia. The
      severity of this anomaly has important implications for postoperative hearing
      results. These findings suggest that ossicular chain reconstruction should be
      performed in moderately or severely fibrous cases.

PMID- 24449794
TI  - Raoultella electrica sp. nov., isolated from anodic biofilms of a glucose-fed
      microbial fuel cell.
AB  - A Gram-stain-negative, non-spore-forming, rod-shaped bacterium, designated strain
      1GB(T), was isolated from anodic biofilms of a glucose-fed microbial fuel cell.
      Strain 1GB(T) was facultatively anaerobic and chemo-organotrophic, having both a
      respiratory and a fermentative type of metabolism, and utilized a wide variety of
      sugars as carbon and energy sources. Cells grown aerobically contained Q-8 as the
      major quinone, but excreted Q-9 and a small amount of Q-10 when cultured with an
      electrode serving as the sole electron acceptor. The G+C content of the genomic
      DNA of 1GB(T) was 54.5 mol%. Multilocus sequence typing (MLST) analysis showed
      that strain 1GB(T) represented a distinct lineage within the genus Raoultella
      (98.5-99.4 % 16S rRNA gene sequence similarity and 94.0-96.5 % sequence
      similarity based on the three concatenated housekeeping genes gyrA, rpoB and
      parC. Strain 1GB(T) exhibited DNA-DNA hybridization relatedness of 7-43 % with
      type strains of all established species of the genus Raoultella. On the basis of
      these phenotypic, phylogenetic and genotypic data, the name Raoultella electrica
      sp. nov. is proposed for strain 1GB(T). The type strain is 1GB(T) ( = NBRC
      109676(T) = KCTC 32430(T)). 

PMID- 24449796
TI  - Minimally invasive image-guided cochlear implantation for pediatric patients:
      clinical feasibility study.
AB  - OBJECTIVE: Minimally invasive image-guided cochlear implantation (CI) involves
      accessing the cochlea via a linear path from the lateral skull to the cochlea
      avoiding vital structures including the facial nerve. Herein, we describe and
      demonstrate the feasibility of the technique for pediatric patients. STUDY
      DESIGN: Prospective. SETTING: Children's Hospital. SUBJECTS AND METHODS: Thirteen
      pediatric patients (1.5 to 8 years) undergoing traditional CI participated in
      this Institutional Review Board-approved study. Three fiducial markers were bone
      implanted surrounding the ear, and a CT scan was acquired. The CT scan was
      processed to identify the marker locations and critical structures of the
      temporal bone. A safe linear path was determined to target the cochlea avoiding
      damage to vital structures. A custom microstereotactic frame was fabricated that
      would mount on the fiducial markers and constrain a tool to the desired
      trajectory. After traditional mastoidectomy and prior to cochleostomy, the custom
      microstereotactic frame was mounted on the bone-implanted markers to confirm that
      the achieved trajectory was safe and accurately accessed the cochlea. RESULTS:
      For all the 13 patients, it was possible to determine a safe trajectory to the
      cochlea. Custom microstereotactic frames were validated successfully on 9
      patients. Two of these patients had inner ear malformations, and this technique
      helped the surgeon confirm ideal location for cochleostomy. For patients with
      normal anatomy, the mean and standard deviation of the closest distance of the
      trajectory to facial nerve and chorda tympani were 1.1 +/- 0.3 mm and 1.2 +/- 0.5
      mm, respectively. CONCLUSION: Minimally invasive image-guided CI is feasible for
      pediatric patients.

PMID- 24449797
TI  - Submandibular gland preservation during concurrent neck dissection and transoral
      surgery for oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVES: Analyze the effect of ipsilateral submandibular gland preservation on
      patients undergoing concurrent neck dissection and transoral surgery for
      oropharyngeal squamous cell carcinoma. Evaluate for (1) intraoperative and
      postoperative communications between the oropharynx and neck and (2) oncologic
      outcomes. STUDY DESIGN: Retrospective chart review of prospectively collected
      data. SETTING: Tertiary academic referral center. METHODS AND SUBJECTS:
      Retrospective chart review of patients undergoing transoral laser resection of
      oropharyngeal squamous cell carcinoma with simultaneous neck dissection(s) for
      primary, persistent, recurrent, and second primary disease between January 1999
      and February 2013. Data analyzed for operative technique, pathologic diagnosis,
      postoperative course, complications, and oncologic outcomes. RESULTS: Overall 253
      patients were identified. Of these, 96 patients underwent ipsilateral
      submandibular gland preservation and 157 underwent ipsilateral submandibular
      gland removal at the time of neck dissection. The prevalence of intraoperative
      communication between the neck and oropharynx was significantly lower in cases
      with submandibular gland preservation (2/96, 2.08%) compared to those with
      submandibular gland removal (22/157, 14.13%). No postoperative leaks occurred in
      the gland preservation group (0/96, 0%) compared to a leak prevalence of 8.92%
      (14/157) when the gland was removed (P = .0041). There was no difference in
      local, regional, or distant disease recurrence between submandibular gland
      preservation and gland removal. Similarly, Kaplan-Meier analysis showed no
      difference in disease free survival, disease specific survival, or overall
      survival. CONCLUSIONS: Submandibular gland preservation during neck dissection in
      patients undergoing transoral surgery for oropharyngeal squamous cell carcinoma
      significantly reduces the risk of intraoperative and postoperative salivary leaks
      without compromising oncologic outcomes.

PMID- 24449798
TI  - Inpatient hospital outcomes following injury in Suriname: lessons for prevention.
AB  - Traumatic injury is an important and indiscriminant contributor to mortality.
      Hypothesizing that outcomes from severe injuries do not vary by demographic
      factors or socioeconomic status, this research analyzed the relationship between
      race, ethnicity, injury characteristics, and fatality following hospitalization
      in Suriname. Data were obtained for all hospital episodes in 2008 from the only
      hospital within the greater Paramaribo area that provides emergency department
      services. A logistic regression was used to analyze the subset of 544 non-elderly
      adult trauma victims to assess the contribution of patient demographics and
      anatomic injury severity to outcome, which was defined as mortality during acute
      hospitalization. The specific demographics included were patient age, gender,
      race, and insurance status. Injury severity was measured using the International
      Classification Injury Severity Score. The results indicate that age, insurance
      status, injury type, and injury severity were significant predictors for
      survival. While the uninsured experienced a higher rate of mortality, the model
      suggests this result is not due to physiologic reasons but behavioral and
      socioeconomic. The higher mortality is driven by greater injury severity, which
      increases not only the mortality rate but also the cost of care. Injury severity
      itself, independent of all other factors, is the most important contributor. The
      results suggest that a reduction of 10% in injury severity, around the mean,
      would reduce the probability of mortality by 70%. This suggests that targeting
      risk-taking behavior, perhaps relating to compliance with safety practices (e.g.
      seat belt and helmet laws), driver education, and road safety measures can play
      important roles in reducing mortality and morbidity from injury in Suriname. 

PMID- 24449799
TI  - We love our school toilets: involving primary school students in improving their
      school toilets.
AB  - This article reports on the planning, implementation and evaluation of an
      intervention to improve school students' experience of using the school toilet in
      a primary school in Melbourne, Australia. 20 students from grades 2-6
      participated in focus groups, to discuss what they valued about the school and
      raise awareness of issues they were not happy about. A common theme from all of
      the focus groups was that students reported avoiding use of the school toilets.
      Using the ideas generated from the focus groups, the student council (with input
      from staff), developed a self-administered pre- and post-test questionnaire. This
      was given to 220 students in grades 1-4, aged 6-10 years. Improvements suggested
      by the students were made to the toilet block, and then a post-test was
      administered. Independent t tests were conducted. The pre-test indicated that 71%
      of girls and 65% of boys feared the behaviour of other students in the toilet.
      Overwhelmingly, the qualitative comments focused on poor student behaviour in the
      toilets, with lack of privacy due to student misbehaviour mentioned in 90% of the
      comments. After the toilets were revamped, the greatest gains were made in
      students' attitudes toward the toilets, with a 37% increase in students who
      indicated they now liked the toilet facility. Incidents of vandalism also
      decreased; however, student misconduct in the toilets was still regarded as a
      problem. Involving students in refurbishing their toilets improved how students
      viewed the toilets and reduced vandalism; however, a different intervention is
      required to change inappropriate behaviours in the toilet. 

PMID- 24449800
TI  - Comparison of kinematic and kinetic parameters calculated using a cluster-based
      model and Vicon's plug-in gait.
AB  - Gait analysis is an important clinical tool. A variety of models are used for
      gait analysis, each yielding different results. Errors in model outputs can occur
      due to inaccurate marker placement and skin motion artefacts, which may be
      reduced using a cluster-based model. We aimed to compare a custom-made cluster
      model (ClusBB) with Vicon's plug-in gait. A total of 21 healthy subjects wore
      marker sets for the ClusBB and plug-in gait models simultaneously while walking
      on a 6-m walkway. Marker and force plate data were captured synchronously and
      joint angles/moments were calculated using both models. There was good
      correlation between the models (coefficient of multiple correlations > 0.65) and
      good intra-session correlation for both models (coefficient of multiple
      correlations > 0.80). Inter-subject variability was high, ranging from 15 degrees
      to 40 degrees  in the sagittal plane and 11 degrees  to 52 degrees  in the
      coronal and transverse planes. Intra-subject variability was small for both
      ClusBB and plug-in gait models. Inter-subject variance tended to be high in both
      models for knee abduction/adduction, but particularly so for plug-in gait,
      suggesting that a cluster-based model may reduce the variability. The inter
      subject variance in out-of-sagittal plane data is of particular importance
      clinically, given the reliance on these datasets in clinical decision-making. 

PMID- 24449801
TI  - Experiences of sexuality and intimacy in terminal illness: a phenomenological
      study.
AB  - BACKGROUND: There is a paucity of research considering sexuality and intimacy in
      palliative care. It is therefore unclear whether palliative care professionals
      have a role in addressing these issues with patients and their partners. AIM: To
      understand people's experiences of sexuality and intimacy when living with a
      terminal illness. DESIGN: A Heideggerian hermeneutic (interpretive)
      phenomenological study was undertaken. Data were collected using one-to-one
      conversational interviews. An iterative approach to analysing the narratives was
      used to reveal shared meanings. SETTING/PARTICIPANTS: A total of 27 patients and
      14 partners of patients with either cancer or motor neuron disease were recruited
      from outpatient, community and hospice inpatient units. All participants were
      aware that the illness was life-limiting. FINDINGS: When someone is living with a
      life-limiting illness, their coupled relationship is also dying. In their being
      towards-death-of-the-couple, patients and partners of patients with motor neuron
      disease and terminal cancer experienced connecting and disconnecting within their
      coupled relationship. Becoming-apart-as-a-couple was experienced as loss of
      spontaneity, as lack of reciprocity and as rejection. This was influenced by a
      range of factors including medical treatments, disfigurement and the disabling
      effects of equipment. Some participants experienced re-connecting through
      becoming-closer-as-a-couple, although this was not always sustained. CONCLUSIONS:
      This study sheds new light on people's experiences of sexuality and intimacy when
      living with a terminal illness. The ethos of holistic care requires palliative
      care professionals to provide opportunities for patients and their partners to
      discuss any concerns they might have about their coupled relationship and to
      understand the meanings symptoms have for them.

PMID- 24449802
TI  - The myocardial oxygen supply:demand index revisited.

PMID- 24449803
TI  - New-onset atrial fibrillation is associated with cardiovascular events leading to
      death in a first time myocardial infarction population of 89,703 patients with
      long-term follow-up: a nationwide study.
AB  - BACKGROUND: New-onset atrial fibrillation (AF) is reported to increase the risk
      of death in myocardial infarction (MI) patients. However, previous studies have
      reported conflicting results and no data exist to explain the underlying cause of
      higher death rates in these patients. METHODS AND RESULTS: All patients with
      first acute MI between 1997 and 2009 in Denmark, without prior AF, were
      identified from Danish nationwide administrative registers. The impact of new
      onset AF on all-cause mortality, cardiovascular death, fatal/nonfatal stroke,
      fatal/nonfatal re-infarction and noncardiovascular death, were analyzed by
      multiple time-dependent Cox models and additionally in propensity score matched
      analysis. In 89 703 patients with an average follow-up of 5.0 +/- 3.5 years event
      rates were higher in patients developing AF (n=10 708) versus those staying in
      sinus-rhythm (n=78 992): all-cause mortality 173.9 versus 69.4 per 1000 person
      years, cardiovascular death 137.2 versus 50.0 per 1000 person-years,
      fatal/nonfatal stroke 19.6/19.9 versus 6.2/5.6 per 1000 person-years,
      fatal/nonfatal re-infarction 29.0/60.7 versus 14.2/37.9 per 1000 person-years. In
      time-dependent multiple Cox analyses, new-onset AF remained predictive of
      increased all-cause mortality (HR: 1.9 [95% CI: 1.8 to 2.0]), cardiovascular
      death (HR: 2.1 [2.0 to 2.2]), fatal/nonfatal stroke (HR: 2.3 [2.1 to 2.6]/HR: 2.5
      [2.2 to 2.7]), fatal/nonfatal re-infarction (HR: 1.7 [1.6 to 1.8]/HR: 1.8 [1.7 to
      1.9]), and non- cardiovascular death (HR: 1.4 [1.3 to 1.5]) all P<0.001).
      Propensity-score matched analyses yielded nearly identical results (all P<0.001).
      CONCLUSIONS: New-onset AF after first-time MI is associated with increased
      mortality, which is largely explained by more cardiovascular deaths. Focus on the
      prognostic impact of post-infarct AF is warranted.

PMID- 24449805
TI  - Finding influential users of online health communities: a new metric based on
      sentiment influence.
AB  - OBJECTIVE: Online health communities (OHCs) have become a major source of support
      for people with health problems. This research tries to improve our understanding
      of social influence and to identify influential users in OHCs. The outcome can
      facilitate OHC management, improve community sustainability, and eventually
      benefit OHC users. METHODS: Through text mining and sentiment analysis of users'
      online interactions, the research revealed sentiment dynamics in threaded
      discussions. A novel metric--the number of influential responding replies--was
      proposed to directly measure a user's ability to affect the sentiment of others.
      RESULTS: Using the dataset from a popular OHC, the research demonstrated that the
      proposed metric is highly effective in identifying influential users. In
      addition, combining the metric with other traditional measures further improves
      the identification of influential users.

PMID- 24449804
TI  - IL-6 regulates extracellular matrix remodeling associated with aortic dilation in
      a fibrillin-1 hypomorphic mgR/mgR mouse model of severe Marfan syndrome.
AB  - BACKGROUND: Development of thoracic aortic aneurysms is the most significant
      clinical phenotype in patients with Marfan syndrome. An inflammatory response has
      been described in advanced stages of the disease. Because the hallmark of
      vascular inflammation is local interleukin-6 (IL-6) secretion, we explored the
      role of this proinflammatory cytokine in the formation of aortic aneurysms and
      rupture in hypomorphic fibrillin-deficient mice (mgR/mgR). METHODS AND RESULTS:
      MgR/mgR mice developed ascending aortic aneurysms with significant dilation of
      the ascending aorta by 12 weeks (2.7 +/- 0.1 and 1.3 +/- 0.1 for mgR/mgR versus
      wild-type mice, respectively; P<0.001). IL-6 signaling was increased in mgR/mgR
      aortas measured by increases in IL-6 and SOCS3 mRNA transcripts (P<0.05) and in
      cytokine secretion of IL-6, MCP-1, and GM-CSF (P<0.05). To investigate the role
      of IL-6 signaling, we generated mgR homozygous mice with IL-6 deficiency (DKO).
      The extracellular matrix of mgR/mgR mice showed significant disruption of elastin
      and the presence of dysregulated collagen deposition in the medial-adventitial
      border by second harmonic generation multiphoton autofluorescence microscopy. DKO
      mice exhibited less elastin and collagen degeneration than mgR/mgR mice, which
      was associated with decreased activity of matrix metalloproteinase-9 and had
      significantly reduced aortic dilation (1.0 +/- 0.1 versus 1.6 +/- 0.2 mm change
      from baseline, DKO versus mgR/mgR, P<0.05) that did not affect rupture and
      survival. CONCLUSION: Activation of IL-6-STAT3 signaling contributes to
      aneurysmal dilation in mgR/mgR mice through increased MMP-9 activity, aggravating
      extracellular matrix degradation.

PMID- 24449807
TI  - Medial opening wedge high tibial osteotomy for medial compartment
      overload/arthritis in the varus knee: prognostic factors.
AB  - BACKGROUND: Medial opening wedge high tibial osteotomy (OWHTO) is a widely
      accepted procedure for the treatment of medial compartment arthritis of the knee.
      Compared with closing wedge HTO, however, the outcomes of OWHTO reported in the
      literature are incomplete. PURPOSE: To identify the positive and negative
      prognostic factors related to the outcomes of OWHTO through an evaluation of
      midterm study results and survivorship analysis. STUDY DESIGN: Case series; Level
      of evidence, 4. METHODS: From January 2001 to December 2009, a total of 141
      consecutive OWHTOs were performed in 123 patients. Only patients with symptomatic
      medial knee overload/arthritis were included. The patients were evaluated
      preoperatively and at every follow-up visit with (1) the Knee Society score, (2)
      the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score,
      (3) another self-evaluation scale, (4) long-leg radiographs, and (5) plain
      radiographs. Preoperative, intraoperative, and postoperative variables were
      investigated to find an association with the outcomes. RESULTS: Of the 123
      patients, 15 were lost to follow-up, and 24 were excluded from the study, leaving
      84 patients (99 OWHTOs) for the present study. The mean age of the patients at
      the time of surgery was 54.5 +/- 9.2 years. The mean follow-up was 51.5 +/- 23.8
      months. The Knee Society and WOMAC scores significantly improved after surgery (P
      < .001). The variables significantly related to a poor outcome were (1) age >56
      years (P = .008) and (2) postoperative knee flexion <120 degrees  (P < .001); the
      variables significantly related to a good outcome were (1) Ahlback grade 0
      arthritis of the medial compartment (P < .001) and (2) excellent preoperative
      Knee Society score (P < .001). The Kaplan-Meier analysis showed a survival rate
      of 98.7% at 5 years and 75.9% at 7.5 years. CONCLUSION: With correct indications,
      OWHTO is a reliable procedure for medial knee arthritis/overload. The outcomes
      reported are similar to those from other studies, although the variables related
      to outcomes are slightly different.

PMID- 24449808
TI  - Reliability of the Advanced REACH Tool (ART).
AB  - OBJECTIVES: The aim of this study was to assess the reliability of the Advanced
      REACH Tool (ART) by (i) studying interassessor agreement of the resulting
      exposure estimates generated by the ART mechanistic model, (ii) studying
      interassessor agreement per model parameters of the ART mechanistic model, (iii)
      investigating assessor characteristics resulting in reliable estimates, and (iv)
      estimating the effect of training on assessor agreement. METHODS: Prior to the 1
      day workshop, participants had to assess four scenarios with the ART. During two
      1-day workshops, 54 participants received 3-h training in applying the
      mechanistic model and the technical aspects of the web tool. Afterward, the
      participants assessed another four scenarios. The assessments of the participants
      were compared with gold standard estimates compiled by the workshop instructors.
      Intraclass correlation coefficients (ICCs) were calculated and per model
      parameter and the percentage agreement and Cohen kappa statistics were estimated.
      RESULTS: The ICCs showed good agreement before and almost perfect agreement after
      training. However, substantial variability was observed between individual
      assessors' estimates for an individual scenario. After training, only 42% of the
      assessments lay within a factor of three of the gold standard estimate. The
      reliability appeared to be influenced by several factors: (i) information
      provided by text and video hampered the assessors gaining additional information
      required to make the assessments, (ii) for some parameters, the guidance
      documentation implemented in the tool may have been insufficient, and (iii) in
      some cases, the assessors were not able to implement the information explicitly
      provided. CONCLUSIONS: The ART is an expert tool and extensive training is
      recommended prior to use. Improvements of the guidance documentation, consensus
      procedures, and improving the training methods could improve the reliability of
      ART. Nevertheless, considerable variability can be expected between assessors
      using ART to estimate exposure levels for a given scenario.

PMID- 24449809
TI  - Invasive assessment of pulmonary hypertension: time for a more fluid approach?

PMID- 24449810
TI  - Effects of physical activity and sedentary time on the risk of heart failure.
AB  - BACKGROUND: Although the benefits of physical activity for risk of coronary heart
      disease are well established, less is known about its effects on heart failure
      (HF). The risk of prolonged sedentary behavior on HF is unknown. METHODS AND
      RESULTS: The study cohort included 82 695 men aged>=45 years from the California
      Men's Health Study without prevalent HF who were followed up for 10 years.
      Physical activity, sedentary time, and behavioral covariates were obtained from
      questionnaires, and clinical covariates were determined from electronic medical
      records. Incident HF was identified through International Classification of
      Diseases, Ninth Revision codes recorded in electronic records. During a mean
      follow-up of 7.8 years (646 989 person-years), 3473 men were diagnosed with HF.
      Controlling for sedentary time, sociodemographics, hypertension, diabetes
      mellitus, unfavorable lipid levels, body mass index, smoking, and diet, the
      hazard ratio (95% confidence interval [CI]) of HF in the lowest physical activity
      category compared with those in the highest category was 1.52 (95% CI, 1.39
      1.68). Those in the medium physical activity category were also at increased risk
      (hazard ratio, 1.17 [95% CI, 1.06-1.29]). Controlling for the same covariates and
      physical activity, the hazard ratio (95% CI) of HF in the highest sedentary
      category compared with the lowest was 1.34 (95% CI, 1.21-1.48). Medium sedentary
      time also conveyed risk (hazard ratio, 1.13 [95% CI, 1.04-1.24]). Results showed
      similar trends across white and Hispanic subgroups, body mass index categories,
      baseline hypertension status, and prevalent coronary heart disease. CONCLUSIONS:
      Both physical activity and sedentary time may be appropriate intervention targets
      for preventing HF.

PMID- 24449811
TI  - MicroRNAs in heart failure: is the picture becoming less miRky?

PMID- 24449812
TI  - Valvular heart disease in patients supported with left ventricular assist
      devices.
AB  - Patients with advanced HF and coexisting VHD who undergo LVAD implantation
      constitute a growing population and pose unique challenges in clinical and
      surgical management. Contemporary continuous-flow LVADs alter blood flow dynamics
      and cardiovascular physiology and can induce progression of preexisting VHD or
      lead to de novo VHD. Although we have defined our recommendations for treatment
      options (Table 2), continued changes to device technology, patient selection, and
      surgical techniques will undoubtedly lead to further changes in practice.
      Finally, the rapid growth in the field of mechanical circulatory support
      necessitates collaborative multicenter approaches to study the impact of these
      practice changes in the form of prospective randomized trials.

PMID- 24449813
TI  - Ablation of ventricular tachycardia originating from the papillary muscle of the
      left ventricle early after heart transplantation.

PMID- 24449814
TI  - Dynamic left ventricular assist device inflow obstruction.

PMID- 24449815
TI  - Heart failure and pulsus alternans: an unusual presentation of first-degree heart
      block.

PMID- 24449816
TI  - Emergency parallel mechanical circulatory support for ventricular fibrillation.

PMID- 24449818
TI  - Hyperactive adverse mechanical stress responses in dystrophic heart are coupled
      to transient receptor potential canonical 6 and blocked by cGMP-protein kinase G
      modulation.
AB  - RATIONALE: The heart is exquisitely sensitive to mechanical stimuli to adapt
      rapidly to physiological demands. In muscle lacking dystrophin, such as Duchenne
      muscular dystrophy, increased load during contraction triggers pathological
      responses thought to worsen the disease. The relevant mechanotransducers and
      therapies to target them remain unclear. OBJECTIVES: We tested the role of
      transient receptor potential canonical (TRPC) channels TRPC3 and TRPC6 and their
      modulation by protein kinase G (PKG) in controlling cardiac systolic
      mechanosensing and determined their pathophysiological relevance in an
      experimental model of Duchenne muscular dystrophy. METHODS AND RESULTS:
      Contracting isolated papillary muscles and cardiomyocytes from controls and mice
      genetically lacking either TRPC3 or TRPC6 were subjected to auxotonic load to
      induce stress-stimulated contractility (SSC, gradual rise in force and
      intracellular Ca(2+)). Incubation with cGMP (PKG activator) markedly blunted SSC
      in controls and Trpc3(-/-); whereas in Trpc6(-/-), the resting SSC response was
      diminished and cGMP had no effect. In Duchenne muscular dystrophy myocytes
      (mdx/utrophin deficient), the SSC was excessive and arrhythmogenic. Gene deletion
      or selective drug blockade of TRPC6 or cGMP/PKG activation reversed this
      phenotype. Chronic phosphodiesterase 5A inhibition also normalized abnormal
      mechanosensing while blunting progressive chamber hypertrophy in Duchenne
      muscular dystrophy mice. CONCLUSIONS: PKG is a potent negative modulator of
      cardiac systolic mechanosignaling that requires TRPC6 as the target effector. In
      dystrophic hearts, excess SSC and arrhythmia are coupled to TRPC6 and are
      ameliorated by its targeted suppression or PKG activation. These results
      highlight novel therapeutic targets for this disease.

PMID- 24449819
TI  - Does transendocardial injection of mesenchymal stem cells improve myocardial
      function locally or globally?: An analysis from the Percutaneous Stem Cell
      Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.
AB  - RATIONALE: Transendocardial stem cell injection (TESI) with mesenchymal stem
      cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of
      the injection site remains unknown. OBJECTIVE: To address whether TESI exerts its
      effects at the site of injection only or also in remote areas, we hypothesized
      that segmental myocardial scar and segmental ejection fraction improve to a
      greater extent in injected than in noninjected segments. METHODS AND RESULTS:
      Biplane ventriculographic and endocardial tracings were recorded. TESI was guided
      to 10 sites in infarct-border zones. Sites were mapped according to the 17
      myocardial segment model. As a result, 510 segments were analyzed in 30 patients
      before and 13 months after TESI. Segmental early enhancement defect (a measure of
      scar size) was reduced by TESI in both injected (-43.7 +/- 4.4%; n=95; P<0.01)
      and noninjected segments (-25.1 +/- 7.8%; n=148; P<0.001; between-group
      comparison P<0.05). Conversely, segmental ejection fraction (a measure of
      contractile performance) improved in injected scar segments (19.9 +/- 3.3-26.3 +/
      3.5%; P=0.003) but not in noninjected scar segments (21.3 +/- 2.6-23.5 +/- 3.2%;
      P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection
      fraction in injected scar segments improved to a greater degree in patients with
      baseline segmental ejection fraction <20% (12.1 +/- 1.2-19.9 +/- 2.7%; n=18;
      P=0.003), versus <20% (31.7 +/- 3.4-35.5 +/- 3.3%; n=12; P=0.33, between-group
      comparison P<0.0001). CONCLUSIONS: These findings illustrate a dichotomy in
      regional responses to TESI. Although scar size reduction was evident in all scar
      segments, scar size reduction and ventricular functional responses preferentially
      occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was
      greatest when segmental left ventricular dysfunction was severe.

PMID- 24449820
TI  - Degradation of platelet-von Willebrand factor complexes by plasmin: an
      alternative/backup mechanism to ADAMTS13.

PMID- 24449821
TI  - Plasmin cleavage of von Willebrand factor as an emergency bypass for ADAMTS13
      deficiency in thrombotic microangiopathy.
AB  - BACKGROUND: Von Willebrand factor (VWF) multimer size is controlled through
      continuous proteolysis by ADAMTS13 (a disintegrin and metalloproteinase with a
      thrombospondin type I motif, member 13). This prevents spontaneous platelet
      agglutination and microvascular obstructions. ADAMTS13 deficiency is associated
      with thrombotic thrombocytopenic purpura, in which life-threatening episodes of
      microangiopathy damage kidneys, heart, and brain. Enigmatically, a complete
      ADAMTS13 deficiency does not lead to continuous microangiopathy. We hypothesized
      that plasmin, the key enzyme of the fibrinolytic system, serves as a
      physiological backup enzyme for ADAMTS13 in the degradation of pathological
      platelet-VWF complexes. METHODS AND RESULTS: Using real-time microscopy, we
      determined that plasmin rapidly degrades platelet-VWF complexes on endothelial
      cells in absence of ADAMTS13, after activation by urokinase-type plasminogen
      activator or the thrombolytic agent streptokinase. Similarly, plasmin degrades
      platelet-VWF complexes in platelet agglutination studies. Plasminogen directly
      binds to VWF and its A1 domain in a lysine-dependent manner, as determined by
      enzyme-linked immunosorbent assay. Plasma levels of plasmin-alpha2-antiplasmin
      complexes increase with the extent of thrombocytopenia in patients with acute
      episodes of thrombotic thrombocytopenic purpura, independent of ADAMTS13
      activity. This indicates that plasminogen activation takes place during
      microangiopathy. Finally, we show that the thrombolytic agent streptokinase has
      therapeutic value for Adamts13(-/-) mice in a model of thrombotic
      thrombocytopenic purpura. CONCLUSIONS: We propose that plasminogen activation on
      endothelial cells acts as a natural backup for ADAMTS13 to degrade obstructive
      platelet-VWF complexes. Our findings indicate that thrombolytic agents may have
      therapeutic value in the treatment of microangiopathies and may be useful to
      bypass inhibitory antibodies against ADAMTS13 that cause thrombotic
      thrombocytopenic purpura.

PMID- 24449822
TI  - Rapid induction of androgen receptor splice variants by androgen deprivation in
      prostate cancer.
AB  - PURPOSE: Mechanisms mediating androgen receptor (AR) reactivation in prostate
      cancer that progresses after castration (castration-resistant prostate cancer;
      CRPC) and subsequent treatment with abiraterone (CYP17A1 inhibitor that further
      suppresses androgen synthesis) remain unclear. EXPERIMENTAL DESIGN: Prostate
      cancer xenografts were examined to identify mechanism of progression after
      castration and abiraterone. RESULTS: AR reactivation in abiraterone-resistant
      VCaP xenografts was not associated with restoration of intratumoral androgens or
      alterations in AR coregulators. In contrast, mRNA encoding full-length AR (AR-FL)
      and a constitutively active splice variant (AR-V7) were increased compared with
      xenografts before castration, with an increase in AR-V7 relative to AR-FL. This
      shift toward AR-V7 was due to a feedback mechanism whereby the androgen-liganded
      AR stimulates expression of proteins that suppress generation of AR-V7 relative
      to AR-FL transcripts. However, despite the increases in AR-V7 mRNA, it remained a
      minor transcript (<1%) relative to AR-FL in resistant VCaP xenografts and CRPC
      clinical samples. AR-V7 protein expression was similarly low relative to AR-FL in
      castration-resistant VCaP xenografts and androgen-deprived VCaP cells, but the
      weak basal AR activity in these latter cells was further repressed by AR-V7
      siRNA. CONCLUSIONS: AR-V7 at these low levels is not adequate to restore AR
      activity, but its rapid induction after androgen deprivation allows tumors to
      retain basal AR activity that may be needed for survival until more potent
      mechanisms emerge to activate AR. Agents targeting AR splice variants may be most
      effective when used very early in conjunction with therapies targeting the AR
      ligand-binding domain.

PMID- 24449823
TI  - TGF-beta-induced upregulation of malat1 promotes bladder cancer metastasis by
      associating with suz12.
AB  - PURPOSE: TGF-beta promotes tumor invasion and metastasis by inducing an
      epithelial-mesenchymal transition (EMT). However, the underlying mechanisms
      causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown
      to play important regulatory roles in cancer progression. The lncRNA malat1
      (metastasis associated lung adenocarcinoma transcript 1) is a critical regulator
      of the metastasis phenotype of lung cancer cells. EXPERIMENTAL DESIGN: We,
      therefore, investigated whether TGF-beta regulates malat1 expression to promote
      tumor metastasis of bladder cancer. The expression levels of malat1 and EMT
      markers were assayed in specimens of bladder cancer. The role of malat1 in
      regulating bladder cancer metastasis was evaluated in cell and animal models.
      RESULTS: TGF-beta induces malat1 expression and EMT in bladder cancer cells.
      malat1 overexpression is significantly correlated with poor survival in patients
      with bladder cancer. malat1 and E-cadherin expression is negatively correlated in
      vitro and in vivo. malat1 knockdown inhibits TGF-beta-induced EMT. malat1 is
      associated with suppressor of zeste 12 (suz12), and this association results in
      decrease of E-cadherin expression and increase of N-cadherin and fibronectin
      expression. Furthermore, targeted inhibition of malat1 or suz12 suppresses the
      migratory and invasive properties induced by TGF-beta. Finally, we demonstrated
      that malat1 or suz12 knockdown inhibits tumor metastasis in animal models.
      CONCLUSION: These data suggest that malat1 is an important mediator of TGF-beta
      induced EMT, and suggest that malat1 inhibition may represent a promising
      therapeutic option for suppressing bladder cancer progression.

PMID- 24449824
TI  - hERG1 channels regulate VEGF-A secretion in human gastric cancer:
      clinicopathological correlations and therapeutical implications.
AB  - PURPOSE: hERG1 channels are aberrantly expressed in several types of human
      cancers, where they affect different aspects of cancer cell behavior. A thorough
      analysis of the functional role and clinical significance of hERG1 channels in
      gastric cancer is still lacking. EXPERIMENTAL DESIGN: hERG1 expression was tested
      in a wide (508 samples) Italian cohort of surgically resected patients with
      gastric cancer, by immunohistochemistry and real-time quantitative PCR. The
      functional link between hERG1 and the VEGF-A was studied in different gastric
      cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in
      vivo in xenograft mouse models. RESULTS: hERG1 was positive in 69% of the
      patients and positivity correlated with Lauren's intestinal type, fundus
      localization of the tumor, G1-G2 grading, I and II tumor-node-metastasis stage,
      and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT
      dependent regulation of the transcriptional activity of the hypoxia inducible
      factor. Treatment of immunodeficient mice xenografted with human gastric cancer
      cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired
      tumor growth more than single-drug treatments. CONCLUSION: Our results show that
      hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages;
      (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be
      exploited to identify a gastric cancer patients' group where a combined treatment
      with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed.

PMID- 24449825
TI  - Inactivation of the CDKN2A tumor-suppressor gene by deletion or methylation is
      common at diagnosis in follicular lymphoma and associated with poor clinical
      outcome.
AB  - PURPOSE: Follicular lymphoma, the most common indolent lymphoma, is clinically
      heterogeneous. CDKN2A encodes the tumor suppressors p16(INK4a) and p14(ARF) and
      frequently suffers deleterious alterations in cancer. We investigated the
      hypothesis that deletion or hypermethylation of CDKN2A might identify follicular
      lymphoma cases with distinct clinical or pathologic features potentially amenable
      to tailored clinical management. EXPERIMENTAL DESIGN: Deletion of CDKN2A was
      detected in pretreatment biopsy specimens using a single nucleotide polymorphism
      based approach or endpoint PCR, and methylation of CpG elements in CDKN2A was
      quantified by methylation-specific PCR. Correlations between CDKN2A status and
      pathologic or clinical characteristics, including overall survival (OS), were
      investigated in 106 cases using standard statistical methods. RESULTS: Deletion
      of CDKN2A was detected in 9 of 111 samples (8%) and methylation was detectable in
      22 of 113 (19%). CDKN2A was either deleted or methylated in 29 of 106 cases (27%)
      and this status was associated with inferior OS especially among patients treated
      with rituximab (P = 0.004). CDKN2A deletion or methylation was associated with
      more advanced age (P = 0.012) and normal hemoglobin (P = 0.05) but not with sex,
      FLIPI score, ECOG stage, LDH, performance status, number of involved nodal sites,
      B symptoms, histologic grade, the presence of a component of diffuse large B-cell
      lymphoma, proliferation index, or other pathologic factors. CONCLUSIONS: Our
      results show that deletion or methylation of CDKN2A is relatively common in
      pretreatment follicular lymphoma biopsy specimens and defines a group of cases
      associated with reduced survival in the rituximab era presumably on the basis of
      more aggressive disease biology.

PMID- 24449826
TI  - Calcium/Calmodulin-dependent protein kinase II and its endogenous inhibitor alpha
      in medullary thyroid cancer.
AB  - PURPOSE: Calcium/calmodulin-dependent kinase II (CaMKII) is involved in the
      regulation of cell proliferation. Its endogenous inhibitor (hCaKIINalpha) is
      expressed in some cell types. We determined the role of CaMKII in RET-stimulated
      proliferation and hCaMKIINalpha in medullary thyroid carcinoma (MTC).
      EXPERIMENTAL DESIGN: We analyzed the role of RET mutants on CaMKII activation in
      NIH3T3 and in MTC cell lines, and determined the effect of CaMKII inhibition on
      RET/ERK pathway and cell proliferation. Then the expression of hCaKIINalpha mRNA
      was determined by real-time PCR in primary MTC and it was correlated with some
      clinicopathologic parameters. RESULTS: RET(C634Y) and RET(M918T) mutants
      expressed in NIH3T3 cells induced CaMKII activation. CaMKII was activated in
      unstimulated MTC cells carrying the same RET mutants and it was inhibited by RET
      inhibition. Inhibition of CaMKII in these cells induced a reduction of Raf-1,
      MEK, and ERK phosphorylation, cyclin D expression, and cell proliferation.
      hCaKIINalpha mRNA expression in primary MTC was very variable and did not
      correlate with gender and age at diagnosis. Serum calcitonin, (R(2) = 0.032; P =
      0.017), tumor volume (P = 0.0079), lymph node metastasis (P = 0.033), and staging
      (P = 0.0652) were negatively correlated with the hCaKIINalpha mRNA expression.
      CONCLUSIONS: CaMKII is activated by RET mutants and is activated at baseline in
      MTC cells where it mediates the oncogenic pathway leading to cell proliferation.
      The mRNA expression of its endogenous inhibitor hCaKIINalpha inversely correlates
      with the severity of MTC. CaMKII might represent a new target for MTC therapy and
      hCaKIINalpha is a marker of disease extension.

PMID- 24449827
TI  - Grand challenges for archaeology.

PMID- 24449828
TI  - Fred Sanger: a memorial tribute.

PMID- 24449829
TI  - TGF-beta and lung fluid balance in ARDS.

PMID- 24449831
TI  - Pelvic girdle and fin of Tiktaalik roseae.
AB  - A major challenge in understanding the origin of terrestrial vertebrates has been
      knowledge of the pelvis and hind appendage of their closest fish relatives. The
      pelvic girdle and appendage of tetrapods is dramatically larger and more robust
      than that of fish and contains a number of structures that provide greater
      musculoskeletal support for posture and locomotion. The discovery of pelvic
      material of the finned elpistostegalian, Tiktaalik roseae, bridges some of these
      differences. Multiple isolated pelves have been recovered, each of which has been
      prepared in three dimensions. Likewise, a complete pelvis and partial pelvic fin
      have been recovered in association with the type specimen. The pelves of
      Tiktaalik are paired and have broad iliac processes, flat and elongate pubes, and
      acetabulae that form a deep socket rimmed by a robust lip of bone. The pelvis is
      greatly enlarged relative to other finned tetrapodomorphs. Despite the
      enlargement and robusticity of the pelvis of Tiktaalik, it retains primitive
      features such as the lack of both an attachment for the sacral rib and an
      ischium. The pelvic fin of Tiktaalik (NUFV 108) is represented by fin rays and
      three endochondral elements: other elements are not preserved. The mosaic of
      primitive and derived features in Tiktaalik reveals that the enhancement of the
      pelvic appendage of tetrapods and, indeed, a trend toward hind limb-based
      propulsion have antecedents in the fins of their closest relatives. 

PMID- 24449832
TI  - How to make spinal motor neurons.
AB  - All muscle movements, including breathing, walking, and fine motor skills rely on
      the function of the spinal motor neuron to transmit signals from the brain to
      individual muscle groups. Loss of spinal motor neuron function underlies several
      neurological disorders for which treatment has been hampered by the inability to
      obtain sufficient quantities of primary motor neurons to perform mechanistic
      studies or drug screens. Progress towards overcoming this challenge has been
      achieved through the synthesis of developmental biology paradigms and advances in
      stem cell and reprogramming technology, which allow the production of motor
      neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron
      development has been applied to allow generation of motor neurons either from
      pluripotent stem cells by directed differentiation and transcriptional
      programming, or from somatic cells by direct lineage conversion. Finally, we
      discuss methods to evaluate the molecular and functional properties of motor
      neurons generated through each of these techniques. 

PMID- 24449834
TI  - miR-335 promotes mesendodermal lineage segregation and shapes a transcription
      factor gradient in the endoderm.
AB  - Transcription factors (TFs) pattern developing tissues and determine cell fates;
      however, how spatio-temporal TF gradients are generated is ill defined. Here we
      show that miR-335 fine-tunes TF gradients in the endoderm and promotes
      mesendodermal lineage segregation. Initially, we identified miR-335 as a
      regulated intronic miRNA in differentiating embryonic stem cells (ESCs). miR-335
      is encoded in the mesoderm-specific transcript (Mest) and targets the 3'-UTRs of
      the endoderm-determining TFs Foxa2 and Sox17. Mest and miR-335 are co-expressed
      and highly accumulate in the mesoderm, but are transiently expressed in endoderm
      progenitors. Overexpression of miR-335 does not affect initial mesendoderm
      induction, but blocks Foxa2- and Sox17-mediated endoderm differentiation in ESCs
      and ESC-derived embryos. Conversely, inhibition of miR-335 activity leads to
      increased Foxa2 and Sox17 protein accumulation and endoderm formation.
      Mathematical modeling predicts that transient miR-335 expression in endoderm
      progenitors shapes a TF gradient in the endoderm, which we confirm by functional
      studies in vivo. Taken together, our results suggest that miR-335 targets
      endoderm TFs for spatio-temporal gradient formation in the endoderm and to
      stabilize lineage decisions during mesendoderm formation. 

PMID- 24449833
TI  - Lung development: orchestrating the generation and regeneration of a complex
      organ.
AB  - The respiratory system, which consists of the lungs, trachea and associated
      vasculature, is essential for terrestrial life. In recent years, extensive
      progress has been made in defining the temporal progression of lung development,
      and this has led to exciting discoveries, including the derivation of lung
      epithelium from pluripotent stem cells and the discovery of developmental
      pathways that are targets for new therapeutics. These discoveries have also
      provided new insights into the regenerative capacity of the respiratory system.
      This Review highlights recent advances in our understanding of lung development
      and regeneration, which will hopefully lead to better insights into both
      congenital and acquired lung diseases. 

PMID- 24449835
TI  - Prox1 ablation in hepatic progenitors causes defective hepatocyte specification
      and increases biliary cell commitment.
AB  - The liver has multiple functions that preserve homeostasis. Liver diseases are
      debilitating, costly and often result in death. Elucidating the developmental
      mechanisms that establish the liver's architecture or generate the cellular
      diversity of this organ should help advance the prevention, diagnosis and
      treatment of hepatic diseases. We previously reported that migration of early
      hepatic precursors away from the gut epithelium requires the activity of the
      homeobox gene Prox1. Here, we show that Prox1 is a novel regulator of cell
      differentiation and morphogenesis during hepatogenesis. Prox1 ablation in
      bipotent hepatoblasts dramatically reduced the expression of multiple hepatocyte
      genes and led to very defective hepatocyte morphogenesis. As a result, abnormal
      epithelial structures expressing hepatocyte and cholangiocyte markers or
      resembling ectopic bile ducts developed in the Prox1-deficient liver parenchyma.
      By contrast, excessive commitment of hepatoblasts into cholangiocytes, premature
      intrahepatic bile duct morphogenesis, and biliary hyperplasia occurred in
      periportal areas of Prox1-deficient livers. Together, these abnormalities
      indicate that Prox1 activity is necessary to correctly allocate cell fates in
      liver precursors. These results increase our understanding of differentiation
      anomalies in pathological conditions and will contribute to improving stem cell
      protocols in which differentiation is directed towards hepatocytes and
      cholangiocytes. 

PMID- 24449836
TI  - Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of
      oligodendrocyte differentiation in the developing CNS.
AB  - In the central nervous system (CNS), oligodendrocyte maturation and axonal
      myelination occur on a predictable schedule, but the underlying timing mechanisms
      are largely unknown. In the present study, we demonstrate that Nkx2.2 homeodomain
      transcription factor is a key regulator for the timing of oligodendrocyte
      differentiation during development. Whereas induced expression of Nkx2.2 in early
      oligodendrocyte precursor cells (OPCs) causes precocious differentiation of
      oligodendrocytes, conditional ablation of Nkx2.2 temporally delays
      oligodendrocyte maturation. Moreover, Nkx2.2 can directly bind to the promoter of
      platelet-derived growth factor receptor alpha (Pdgfra) and repress its gene
      expression. Genetic ablation of Pdgfra mimics the effect of Nkx2.2 overexpression
      in accelerating OPC differentiation in the developing spinal cord. Together, our
      findings strongly suggest that Nkx2.2 functions as a major 'switch' to turn off
      Pdgfra signaling in OPCs and initiate the intrinsic program for oligodendrocyte
      differentiation. 

PMID- 24449837
TI  - Netrin 1 and Dcc signalling are required for confinement of central axons within
      the central nervous system.
AB  - The establishment of anatomically stereotyped axonal projections is fundamental
      to neuronal function. While most neurons project their axons within the central
      nervous system (CNS), only axons of centrally born motoneurons and peripherally
      born sensory neurons link the CNS and peripheral nervous system (PNS) together by
      navigating through specialized CNS/PNS transition zones. Such selective
      restriction is of importance because inappropriate CNS axonal exit could lead to
      loss of correct connectivity and also to gain of erroneous functions. However, to
      date, surprisingly little is known about the molecular-genetic mechanisms that
      regulate how central axons are confined within the CNS during development. Here,
      we show that netrin 1/Dcc/Unc5 chemotropism contributes to axonal confinement
      within the CNS. In both Ntn1 and Dcc mutant mouse embryos, some spinal
      interneuronal axons exit the CNS by traversing the CNS/PNS transition zones
      normally reserved for motor and sensory axons. We provide evidence that netrin 1
      signalling preserves CNS/PNS axonal integrity in three ways: (1) netrin 1/Dcc
      ventral attraction diverts axons away from potential exit points; (2) a Dcc/Unc5c
      dependent netrin 1 chemoinhibitory barrier in the dorsolateral spinal cord
      prevents interneurons from being close to the dorsal CNS/PNS transition zone; and
      (3) a netrin 1/Dcc-dependent, Unc5c-independent mechanism that actively prevents
      exit from the CNS. Together, these findings provide insights into the molecular
      mechanisms that maintain CNS/PNS integrity and, to the best of our knowledge,
      present the first evidence that chemotropic signalling regulates interneuronal
      CNS axonal confinement in vertebrates. 

PMID- 24449839
TI  - Roles for FGF in lamprey pharyngeal pouch formation and skeletogenesis highlight
      ancestral functions in the vertebrate head.
AB  - A defining feature of vertebrates (craniates) is a pronounced head supported and
      protected by a cellularized endoskeleton. In jawed vertebrates (gnathostomes),
      the head skeleton is made of rigid three-dimensional elements connected by
      joints. By contrast, the head skeleton of modern jawless vertebrates (agnathans)
      consists of thin rods of flexible cellular cartilage, a condition thought to
      reflect the ancestral vertebrate state. To better understand the origin and
      evolution of the gnathostome head skeleton, we have been analyzing head skeleton
      development in the agnathan, lamprey. The fibroblast growth factors FGF3 and FGF8
      have various roles during head development in jawed vertebrates, including
      pharyngeal pouch morphogenesis, patterning of the oral skeleton and
      chondrogenesis. We isolated lamprey homologs of FGF3, FGF8 and FGF receptors and
      asked whether these functions are ancestral features of vertebrate development or
      gnathostome novelties. Using gene expression and pharmacological agents, we found
      that proper formation of the lamprey head skeleton requires two phases of FGF
      signaling: an early phase during which FGFs drive pharyngeal pouch formation, and
      a later phase when they directly regulate skeletal differentiation and
      patterning. In the context of gene expression and functional studies in
      gnathostomes, our results suggest that these roles for FGFs arose in the first
      vertebrates and that the evolution of the jaw and gnathostome cellular cartilage
      was driven by changes developmentally downstream from pharyngeal FGF signaling. 

PMID- 24449838
TI  - A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain
      development in the absence of its paralog.
AB  - The histone deacetylases HDAC1 and HDAC2 are crucial regulators of chromatin
      structure and gene expression, thereby controlling important developmental
      processes. In the mouse brain, HDAC1 and HDAC2 exhibit different developmental
      stage- and lineage-specific expression patterns. To examine the individual
      contribution of these deacetylases during brain development, we deleted different
      combinations of Hdac1 and Hdac2 alleles in neural cells. Ablation of Hdac1 or
      Hdac2 by Nestin-Cre had no obvious consequences on brain development and
      architecture owing to compensation by the paralog. By contrast, combined deletion
      of Hdac1 and Hdac2 resulted in impaired chromatin structure, DNA damage,
      apoptosis and embryonic lethality. To dissect the individual roles of HDAC1 and
      HDAC2, we expressed single alleles of either Hdac1 or Hdac2 in the absence of the
      respective paralog in neural cells. The DNA-damage phenotype observed in double
      knockout brains was prevented by expression of a single allele of either Hdac1 or
      Hdac2. Strikingly, Hdac1(-/-)Hdac2(+/-) brains showed normal development and no
      obvious phenotype, whereas Hdac1(+/-)Hdac2(-/-) mice displayed impaired brain
      development and perinatal lethality. Hdac1(+/-)Hdac2(-/-) neural precursor cells
      showed reduced proliferation and premature differentiation mediated by
      overexpression of protein kinase C, delta, which is a direct target of HDAC2.
      Importantly, chemical inhibition or knockdown of protein kinase C delta was
      sufficient to rescue the phenotype of neural progenitor cells in vitro. Our data
      indicate that HDAC1 and HDAC2 have a common function in maintaining proper
      chromatin structures and show that HDAC2 has a unique role by controlling the
      fate of neural progenitors during normal brain development. 

PMID- 24449840
TI  - Hoxb1b controls oriented cell division, cell shape and microtubule dynamics in
      neural tube morphogenesis.
AB  - Hox genes are classically ascribed to function in patterning the anterior
      posterior axis of bilaterian animals; however, their role in directing molecular
      mechanisms underlying morphogenesis at the cellular level remains largely
      unstudied. We unveil a non-classical role for the zebrafish hoxb1b gene, which
      shares ancestral functions with mammalian Hoxa1, in controlling progenitor cell
      shape and oriented cell division during zebrafish anterior hindbrain neural tube
      morphogenesis. This is likely distinct from its role in cell fate acquisition and
      segment boundary formation. We show that, without affecting major components of
      apico-basal or planar cell polarity, Hoxb1b regulates mitotic spindle rotation
      during the oriented neural keel symmetric mitoses that are required for normal
      neural tube lumen formation in the zebrafish. This function correlates with a non
      cell-autonomous requirement for Hoxb1b in regulating microtubule plus-end
      dynamics in progenitor cells in interphase. We propose that Hox genes can
      influence global tissue morphogenesis by control of microtubule dynamics in
      individual cells in vivo. 

PMID- 24449842
TI  - Reelin and CXCL12 regulate distinct migratory behaviors during the development of
      the dopaminergic system.
AB  - The proper functioning of the dopaminergic system requires the coordinated
      formation of projections extending from dopaminergic neurons in the substantia
      nigra (SN), ventral tegmental area (VTA) and retrorubral field to a wide array of
      forebrain targets including the striatum, nucleus accumbens and prefrontal
      cortex. The mechanisms controlling the assembly of these distinct dopaminergic
      cell clusters are not well understood. Here, we have investigated in detail the
      migratory behavior of dopaminergic neurons giving rise to either the SN or the
      medial VTA using genetic inducible fate mapping, ultramicroscopy, time-lapse
      imaging, slice culture and analysis of mouse mutants. We demonstrate that neurons
      destined for the SN migrate first radially and then tangentially, whereas neurons
      destined for the medial VTA undergo primarily radial migration. We show that
      tangentially migrating dopaminergic neurons express the components of the reelin
      signaling pathway, whereas dopaminergic neurons in their initial, radial
      migration phase express CXC chemokine receptor 4 (CXCR4), the receptor for the
      chemokine CXC motif ligand 12 (CXCL12). Perturbation of reelin signaling
      interferes with the speed and orientation of tangentially, but not radially,
      migrating dopaminergic neurons and results in severe defects in the formation of
      the SN. By contrast, CXCR4/CXCL12 signaling modulates the initial migration of
      dopaminergic neurons. With this study, we provide the first molecular and
      functional characterization of the distinct migratory pathways taken by
      dopaminergic neurons destined for SN and VTA, and uncover mechanisms that
      regulate different migratory behaviors of dopaminergic neurons. 

PMID- 24449841
TI  - Dendrite architecture organized by transcriptional control of the F-actin
      nucleator Spire.
AB  - The architectures of dendritic trees are crucial for the wiring and function of
      neuronal circuits because they determine coverage of receptive territories, as
      well as the nature and strength of sensory or synaptic inputs. Here, we describe
      a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in
      Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription
      factor, and its control of the F-actin cytoskeleton through Spire (Spir), an
      actin nucleation protein. Loss of Lola from da neurons reduced the overall length
      of dendritic arbors, increased the expression of Spir, and produced inappropriate
      F-actin-rich dendrites at positions too near the cell soma. Selective removal of
      Lola from only class IV da neurons decreased the evasive responses of larvae to
      nociception. The increased Spir expression contributed to the abnormal F-actin
      rich dendrites and the decreased nocifensive responses because both were
      suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit
      expression of Spir to appropriate levels within da neurons. We found Spir to be
      expressed in dendritic arbors and to be important for their development. Removal
      of Spir from class IV da neurons reduced F-actin levels and total branch number,
      shifted the position of greatest branch density away from the cell soma, and
      compromised nocifensive behavior. We conclude that the Lola-Spir pathway is
      crucial for the spatial arrangement of branches within dendritic trees and for
      neural circuit function because it provides balanced control of the F-actin
      cytoskeleton. 

PMID- 24449843
TI  - Multiple developmental mechanisms regulate species-specific jaw size.
AB  - Variation in jaw size during evolution has been crucial for the adaptive
      radiation of vertebrates, yet variation in jaw size during development is often
      associated with disease. To test the hypothesis that early developmental events
      regulating neural crest (NC) progenitors contribute to species-specific
      differences in size, we investigated mechanisms through which two avian species,
      duck and quail, achieve their remarkably different jaw size. At early stages,
      duck exhibit an anterior shift in brain regionalization yielding a shorter,
      broader, midbrain. We find no significant difference in the total number of pre
      migratory NC; however, duck concentrate their pre-migratory NC in the midbrain,
      which contributes to an increase in size of the post-migratory NC population
      allocated to the mandibular arch. Subsequent differences in proliferation lead to
      a progressive increase in size of the duck mandibular arch relative to that of
      quail. To test the role of pre-migratory NC progenitor number in regulating jaw
      size, we reduced and augmented NC progenitors. In contrast to previous reports of
      regeneration by NC precursors, we find that neural fold extirpation results in a
      loss of NC precursors. Despite this reduction in their numbers, post-migratory NC
      progenitors compensate, producing a symmetric and normal-sized jaw. Our results
      suggest that evolutionary modification of multiple aspects of NC cell biology,
      including NC allocation within the jaw primordia and NC-mediated proliferation,
      have been important to the evolution of jaw size. Furthermore, our finding of NC
      post-migratory compensatory mechanisms potentially extends the developmental time
      frame for treatments of disease or injury associated with NC progenitor loss. 

PMID- 24449844
TI  - Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination
      and differentiation.
AB  - Delamination plays a pivotal role during normal development and cancer. Previous
      work has demonstrated that delamination and epithelial cell movement within the
      plane of an epithelium are associated with a change in cellular phenotype.
      However, how this positional change is linked to differentiation remains unknown.
      Using the developing mouse pancreas as a model system, we show that beta cell
      delamination and differentiation are two independent events, which are controlled
      by Cdc42/N-WASP signaling. Specifically, we show that expression of
      constitutively active Cdc42 in beta cells inhibits beta cell delamination and
      differentiation. These processes are normally associated with junctional actin
      and cell-cell junction disassembly and the expression of fate-determining
      transcription factors, such as Isl1 and MafA. Mechanistically, we demonstrate
      that genetic ablation of N-WASP in beta cells expressing constitutively active
      Cdc42 partially restores both delamination and beta cell differentiation. These
      findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell
      autonomously control not only epithelial delamination but also cell
      differentiation during mammalian organogenesis. 

PMID- 24449845
TI  - A nutrient-sensitive restriction point is active during retinal progenitor cell
      differentiation.
AB  - In many growing tissues, slowly dividing stem cells give rise to rapidly
      proliferating progenitors that eventually exit the cell cycle and differentiate.
      Growth rates are limited by nutrient availability, but it is unclear which steps
      of the proliferation-differentiation programme are particularly sensitive to fuel
      supplies. We examined how nutrient deprivation (ND) affects stem and progenitor
      cells in the ciliary marginal zone (CMZ) of the amphibian retina, a well
      characterised neurogenic niche. We show that ND specifically blocks the
      proliferation and differentiation of progenitor cells through an mTOR-mediated
      mechanism. By contrast, the identity and proliferation of retinal stem cells are
      insensitive to ND and mTOR inhibition. Re-feeding starved retinas in vitro
      rescues both proliferation and differentiation, and activation of mTOR is
      sufficient to stimulate differentiation even in ND retinas. These results suggest
      that an mTOR-mediated restriction point operates in vivo to couple nutrient
      abundance to the proliferation and differentiation programme in retinal
      progenitor cells. 

PMID- 24449846
TI  - Targeted transgene integration overcomes variability of position effects in
      zebrafish.
AB  - Zebrafish transgenesis is increasingly popular owing to the optical transparency
      and external development of embryos, which provide a scalable vertebrate model
      for in vivo experimentation. The ability to express transgenes in a tightly
      controlled spatio-temporal pattern is an important prerequisite for exploitation
      of zebrafish in a wide range of biomedical applications. However, conventional
      transgenesis methods are plagued by position effects: the regulatory environment
      of genomic integration sites leads to variation of expression patterns of
      transgenes driven by engineered cis-regulatory modules. This limitation
      represents a bottleneck when studying the precise function of cis-regulatory
      modules and their subtle variants or when various effector proteins are to be
      expressed for labelling and manipulation of defined sets of cells. Here, we
      provide evidence for the efficient elimination of variability of position effects
      by developing a PhiC31 integrase-based targeting method. To detect targeted
      integration events, a simple phenotype scoring of colour change in the lens of
      larvae is used. We compared PhiC31-based integration and Tol2 transgenesis in the
      analysis of the activity of a novel conserved enhancer from the developmentally
      regulated neural-specific esrrga gene. Reporter expression was highly variable
      among independent lines generated with Tol2, whereas all lines generated with
      PhiC31 into a single integration site displayed nearly identical, enhancer
      specific reporter expression in brain nuclei. Moreover, we demonstrate that a
      modified integrase system can also be used for the detection of enhancer activity
      in transient transgenesis. These results demonstrate the power of the PhiC31
      based transgene integration for the annotation and fine analysis of
      transcriptional regulatory elements and it promises to be a generally desirable
      tool for a range of applications, which rely on highly reproducible patterns of
      transgene activity in zebrafish. 

PMID- 24449849
TI  - Interview with Dr Iain Simpson, President of the British Cardiovascular Society.

PMID- 24449848
TI  - Prdm9 polymorphism unveils mouse evolutionary tracks.
AB  - PR/SET domain containing 9 (Prdm9) mediates histone modifications such as H3K4me3
      and marks hotspots of meiotic recombination. In many mammalian species, the Prdm9
      gene is highly polymorphic. Prdm9 polymorphism is assumed to play two critical
      roles in evolution: to diversify the spectrum of meiotic recombination hotspots
      and to cause male hybrid sterility, leading to reproductive isolation and
      speciation. Nevertheless, information about Prdm9 sequences in natural
      populations is very limited. In this study, we conducted a comprehensive
      population survey on Prdm9 polymorphism in the house mouse, Mus musculus. Overall
      M. musculus Prdm9 displays an extraordinarily high level of polymorphism,
      particularly in regions encoding zinc finger repeats, which recognize
      recombination hotspots. Prdm9 alleles specific to various M. musculus subspecies
      dominate in subspecies territories. Moreover, introgression into other subspecies
      territories was found for highly divergent Prdm9 alleles associated with t
      haplotype. The results of our phylogeographical analysis suggest that the
      requirement for hotspot diversity depends on geographical range and time span in
      mouse evolution, and that Prdm9 polymorphism has not been maintained by a simple
      balanced selection in the population of each subspecies. 

PMID- 24449850
TI  - Tactile perception and working memory in rats and humans.
AB  - Primates can store sensory stimulus parameters in working memory for subsequent
      manipulation, but until now, there has been no demonstration of this capacity in
      rodents. Here we report tactile working memory in rats. Each stimulus is a
      vibration, generated as a series of velocity values sampled from a normal
      distribution. To perform the task, the rat positions its whiskers to receive two
      such stimuli, "base" and "comparison," separated by a variable delay. It then
      judges which stimulus had greater velocity SD. In analogous experiments, humans
      compare two vibratory stimuli on the fingertip. We demonstrate that the ability
      of rats to hold base stimulus information (for up to 8 s) and their acuity in
      assessing stimulus differences overlap the performance demonstrated by humans.
      This experiment highlights the ability of rats to perceive the statistical
      structure of vibrations and reveals their previously unknown capacity to store
      sensory information in working memory. 

PMID- 24449851
TI  - Gene-centric approach to integrating environmental genomics and biogeochemical
      models.
AB  - Rapid advances in molecular microbial ecology have yielded an unprecedented
      amount of data about the evolutionary relationships and functional traits of
      microbial communities that regulate global geochemical cycles. Biogeochemical
      models, however, are trailing in the wake of the environmental genomics
      revolution, and such models rarely incorporate explicit representations of
      bacteria and archaea, nor are they compatible with nucleic acid or protein
      sequence data. Here, we present a functional gene-based framework for describing
      microbial communities in biogeochemical models by incorporating genomics data to
      provide predictions that are readily testable. To demonstrate the approach in
      practice, nitrogen cycling in the Arabian Sea oxygen minimum zone (OMZ) was
      modeled to examine key questions about cryptic sulfur cycling and dinitrogen
      production pathways in OMZs. Simulations support previous assertions that
      denitrification dominates over anammox in the central Arabian Sea, which has
      important implications for the loss of fixed nitrogen from the oceans.
      Furthermore, cryptic sulfur cycling was shown to attenuate the secondary nitrite
      maximum often observed in OMZs owing to changes in the composition of the
      chemolithoautotrophic community and dominant metabolic pathways. Results
      underscore the need to explicitly integrate microbes into biogeochemical models
      rather than just the metabolisms they mediate. By directly linking geochemical
      dynamics to the genetic composition of microbial communities, the method provides
      a framework for achieving mechanistic insights into patterns and biogeochemical
      consequences of marine microbes. Such an approach is critical for informing our
      understanding of the key role microbes play in modulating Earth's
      biogeochemistry. 

PMID- 24449852
TI  - Nonautonomous contact guidance signaling during collective cell migration.
AB  - Directed migration of groups of cells is a critical aspect of tissue
      morphogenesis that ensures proper tissue organization and, consequently,
      function. Cells moving in groups, unlike single cells, must coordinate their
      migratory behavior to maintain tissue integrity. During directed migration, cells
      are guided by a combination of mechanical and chemical cues presented by
      neighboring cells and the surrounding extracellular matrix. One important class
      of signals that guide cell migration includes topographic cues. Although the
      contact guidance response of individual cells to topographic cues has been
      extensively characterized, little is known about the response of groups of cells
      to topographic cues, the impact of such cues on cell-cell coordination within
      groups, and the transmission of nonautonomous contact guidance information
      between neighboring cells. Here, we explore these phenomena by quantifying the
      migratory response of confluent monolayers of epithelial and fibroblast cells to
      contact guidance cues provided by grooved topography. We show that, in both
      sparse clusters and confluent sheets, individual cells are contact-guided by
      grooves and show more coordinated behavior on grooved versus flat substrates.
      Furthermore, we demonstrate both in vitro and in silico that the guidance signal
      provided by a groove can propagate between neighboring cells in a confluent
      monolayer, and that the distance over which signal propagation occurs is not
      significantly influenced by the strength of cell-cell junctions but is an
      emergent property, similar to cellular streaming, triggered by mechanical
      exclusion interactions within the collective system. 

PMID- 24449853
TI  - Conformal piezoelectric energy harvesting and storage from motions of the heart,
      lung, and diaphragm.
AB  - Here, we report advanced materials and devices that enable high-efficiency
      mechanical-to-electrical energy conversion from the natural contractile and
      relaxation motions of the heart, lung, and diaphragm, demonstrated in several
      different animal models, each of which has organs with sizes that approach human
      scales. A cointegrated collection of such energy-harvesting elements with
      rectifiers and microbatteries provides an entire flexible system, capable of
      viable integration with the beating heart via medical sutures and operation with
      efficiencies of ~2%. Additional experiments, computational models, and results in
      multilayer configurations capture the key behaviors, illuminate essential design
      aspects, and offer sufficient power outputs for operation of pacemakers, with or
      without battery assist. 

PMID- 24449854
TI  - Functional changes of the reward system underlie blunted response to social gaze
      in cocaine users.
AB  - Social interaction deficits in drug users likely impede treatment, increase the
      burden of the affected families, and consequently contribute to the high costs
      for society associated with addiction. Despite its significance, the neural basis
      of altered social interaction in drug users is currently unknown. Therefore, we
      investigated basal social gaze behavior in cocaine users by applying behavioral,
      psychophysiological, and functional brain-imaging methods. In study I, 80 regular
      cocaine users and 63 healthy controls completed an interactive paradigm in which
      the participants' gaze was recorded by an eye-tracking device that controlled the
      gaze of an anthropomorphic virtual character. Valence ratings of different eye
      contact conditions revealed that cocaine users show diminished emotional
      engagement in social interaction, which was also supported by reduced pupil
      responses. Study II investigated the neural underpinnings of changes in social
      reward processing observed in study I. Sixteen cocaine users and 16 controls
      completed a similar interaction paradigm as used in study I while undergoing
      functional magnetic resonance imaging. In response to social interaction, cocaine
      users displayed decreased activation of the medial orbitofrontal cortex, a key
      region of reward processing. Moreover, blunted activation of the medial
      orbitofrontal cortex was significantly correlated with a decreased social network
      size, reflecting problems in real-life social behavior because of reduced social
      reward. In conclusion, basic social interaction deficits in cocaine users as
      observed here may arise from altered social reward processing. Consequently,
      these results point to the importance of reinstatement of social reward in the
      treatment of stimulant addiction. 

PMID- 24449855
TI  - Femtosecond pump-probe microscopy generates virtual cross-sections in historic
      artwork.
AB  - The layering structure of a painting contains a wealth of information about the
      artist's choice of materials and working methods, but currently, no 3D
      noninvasive method exists to replace the taking of small paint samples in the
      study of the stratigraphy. Here, we adapt femtosecond pump-probe imaging,
      previously shown in tissue, to the case of the color palette in paintings, where
      chromophores have much greater variety. We show that combining the contrasts of
      multispectral and multidelay pump-probe spectroscopy permits nondestructive 3D
      imaging of paintings with molecular and structural contrast, even for pigments
      with linear absorption spectra that are broad and relatively featureless. We show
      virtual cross-sectioning capabilities in mockup paintings, with pigment
      separation and nondestructive imaging on an intact 14th century painting (The
      crucifixion by Puccio Capanna). Our approach makes it possible to extract
      microscopic information for a broad range of applications to cultural heritage.

PMID- 24449856
TI  - Functional map of arrestin-1 at single amino acid resolution.
AB  - Arrestins function as adapter proteins that mediate G protein-coupled receptor
      (GPCR) desensitization, internalization, and additional rounds of signaling. Here
      we have compared binding of the GPCR rhodopsin to 403 mutants of arrestin-1
      covering its complete sequence. This comprehensive and unbiased mutagenesis
      approach provides a functional dimension to the crystal structures of inactive,
      preactivated p44 and phosphopeptide-bound arrestins and will guide our
      understanding of arrestin-GPCR complexes. The presented functional map
      quantitatively connects critical interactions in the polar core and along the C
      tail of arrestin. A series of amino acids (Phe375, Phe377, Phe380, and Arg382)
      anchor the C tail in a position that blocks binding of the receptor. Interaction
      of phosphates in the rhodopsin C terminus with Arg29 controls a C-tail exchange
      mechanism in which the C tail of arrestin is released and exposes several charged
      amino acids (Lys14, Lys15, Arg18, Lys20, Lys110, and Lys300) for binding of the
      phosphorylated receptor C terminus. In addition to this arrestin phosphosensor,
      our data reveal several patches of amino acids in the finger (Gln69 and Asp73
      Met75) and the lariat loops (L249-S252 and Y254) that can act as direct binding
      interfaces. A stretch of amino acids at the edge of the C domain (Trp194-Ser199,
      Gly337-Gly340, Thr343, and Thr345) could act as membrane anchor, binding
      interface for a second rhodopsin, or rearrange closer to the central loops upon
      complex formation. We discuss these interfaces in the context of experimentally
      guided docking between the crystal structures of arrestin and light-activated
      rhodopsin. 

PMID- 24449857
TI  - Highly sensitive electronic whiskers based on patterned carbon nanotube and
      silver nanoparticle composite films.
AB  - Mammalian whiskers present an important class of tactile sensors that complement
      the functionalities of skin for detecting wind with high sensitivity and
      navigation around local obstacles. Here, we report electronic whiskers based on
      highly tunable composite films of carbon nanotubes and silver nanoparticles that
      are patterned on high-aspect-ratio elastic fibers. The nanotubes form a
      conductive network matrix with excellent bendability, and nanoparticle loading
      enhances the conductivity and endows the composite with high strain sensitivity.
      The resistivity of the composites is highly sensitive to strain with a pressure
      sensitivity of up to ~8%/Pa for the whiskers, which is >10* higher than all
      previously reported capacitive or resistive pressure sensors. It is notable that
      the resistivity and sensitivity of the composite films can be readily modulated
      by a few orders of magnitude by changing the composition ratio of the components,
      thereby allowing for exploration of whisker sensors with excellent performance.
      Systems consisting of whisker arrays are fabricated, and as a proof of concept,
      real-time two- and three-dimensional gas-flow mapping is demonstrated. The
      ultrahigh sensitivity and ease of fabrication of the demonstrated whiskers may
      enable a wide range of applications in advanced robotics and human-machine
      interfacing. 

PMID- 24449858
TI  - Treating small fiber neuropathy by topical application of a small molecule
      modulator of ligand-induced GFRalpha/RET receptor signaling.
AB  - Small-fiber neuropathy (SFN) is a disorder of peripheral nerves commonly found in
      patients with diabetes mellitus, HIV infection, and those receiving chemotherapy.
      The complexity of disease etiology has led to a scarcity of effective treatments.
      Using two models of progressive SFN, we show that overexpression of glial cell
      line-derived neurotrophic factor (GDNF) in skin keratinocytes or topical
      application of XIB4035, a reported nonpeptidyl agonist of GDNF receptor alpha1
      (GFRalpha1), are effective treatments for SFN. We also demonstrate that XIB4035
      is not a GFRalpha1 agonist, but rather it enhances GFRalpha family receptor
      signaling in conjunction with ligand stimulation. Taken together, our results
      indicate that topical application of GFRalpha/RET receptor signaling modulators
      may be a unique therapy for SFN, and we have identified XIB4035 as a candidate
      therapeutic agent. 

PMID- 24449859
TI  - In vitro analysis suggests that difference in cell movement during direct
      interaction can generate various pigment patterns in vivo.
AB  - Pigment patterns of organisms have invoked strong interest from not only
      biologists but also, scientists in many other fields. Zebrafish is a useful model
      animal for studying the mechanism of pigment pattern formation. The zebrafish
      stripe pattern is primarily two types of pigment cells: melanophores and
      xanthophores. Previous studies have reported that interactions among these
      pigment cells are important for pattern formation. In the recent report, we found
      that the direct contact by xanthophores induces the membrane depolarization of
      melanophores. From analysis of jaguar mutants, it is suggested that the
      depolarization affects the movements of melanophores. To analyze the cell
      movement in detail, we established a unique in vitro system. It allowed us to
      find that WT xanthophores induced repulsive movement of melanophores through
      direct contact. The xanthophores also chased the melanophores. As a result, they
      showed run-and-chase movements. We also analyzed the cell movement of pigment
      cells from jaguar and leopard mutants, which have fuzzy stripes and spot
      patterns, respectively. jaguar cells showed inhibited run-and-chase movements,
      and leopard melanophores scarcely showed repulsive response. Furthermore, we
      paired mutant and WT cells and showed which of the melanophores and xanthophores
      have responsibility for the altered cell movements. These results suggested that
      there is a correspondence relationship between the cell movements and pigment
      patterns. The correspondence relationship highlighted the importance of the cell
      movements in the pattern formation and showed that our system is a quite useful
      system for future study in this field. 

PMID- 24449860
TI  - Toxin Kid uncouples DNA replication and cell division to enforce retention of
      plasmid R1 in Escherichia coli cells.
AB  - Worldwide dissemination of antibiotic resistance in bacteria is facilitated by
      plasmids that encode postsegregational killing (PSK) systems. These produce a
      stable toxin (T) and a labile antitoxin (A) conditioning cell survival to plasmid
      maintenance, because only this ensures neutralization of toxicity. Shortage of
      antibiotic alternatives and the link of TA pairs to PSK have stimulated the
      opinion that premature toxin activation could be used to kill these recalcitrant
      organisms in the clinic. However, validation of TA pairs as therapeutic targets
      requires unambiguous understanding of their mode of action, consequences for cell
      viability, and function in plasmids. Conflicting with widespread notions
      concerning these issues, we had proposed that the TA pair kis-kid (killing
      suppressor-killing determinant) might function as a plasmid rescue system and not
      as a PSK system, but this remained to be validated. Here, we aimed to clarify
      unsettled mechanistic aspects of Kid activation, and of the effects of this for
      kis-kid-bearing plasmids and their host cells. We confirm that activation of Kid
      occurs in cells that are about to lose the toxin-encoding plasmid, and we show
      that this provokes highly selective restriction of protein outputs that inhibits
      cell division temporarily, avoiding plasmid loss, and stimulates DNA replication,
      promoting plasmid rescue. Kis and Kid are conserved in plasmids encoding multiple
      antibiotic resistance genes, including extended spectrum beta-lactamases, for
      which therapeutic options are scarce, and our findings advise against the
      activation of this TA pair to fight pathogens carrying these extrachromosomal
      DNAs. 

PMID- 24449861
TI  - HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the
      US3 protein kinase, and cell derivation.
AB  - STING (stimulator of IFN genes) activates the IFN pathway in response to
      cytosolic DNA. Knockout of STING in mice was reported to exacerbate the
      pathogenicity of herpes simplex virus 1 (HSV-1). Here we report the following:
      (i) STING is stable in cancer-derived HEp-2 or HeLa cells infected with wild-type
      HSV-1 but is degraded in cells infected with mutants lacking the genes encoding
      functional infected cell protein 0 (ICP0), ICP4, or the US3 protein kinase (US3
      PK). In HEp-2 cells, depletion of STING by shRNA results in a decrease in the
      yields of wild-type or DeltaICP0 viruses. (ii) STING is stable throughout
      infection with either wild-type or ICP0 mutant viruses in human embryonic lung
      cells (HEL) or HEK293T cells derived from normal tissues. In these cells,
      depletion of STING results in higher yields of both wild-type and DeltaICP0
      viruses. (iii) The US3-PK is also required for stabilization of IFI16, a nuclear
      DNA sensor. However, the stability of IFI16 does not correlate positively or
      negatively with that of STING. IFI16 is stable in STING-depleted HEL cells
      infected with wild-type virus. In contrast to HEL cells, IFI16 was undetectable
      in STING-depleted HEp-2 cells, and hence the role of HSV-1 in maintaining IFI16
      could not be ascertained. The results indicate that in HSV-1-infected cells the
      stability of IFI16 and the function and stability of STING are dependent on cell
      derivation, the functional integrity of ICP0, and US3-PK, an indication that in
      wild-type virus-infected cells both proteins are actively stabilized. In HEp-2
      cells, the stability of IFI16 requires STING. 

PMID- 24449862
TI  - Novel antiviral host factor, TNK1, regulates IFN signaling through serine
      phosphorylation of STAT1.
AB  - In response to viral infection, the host induces over 300 IFN-stimulated genes
      (ISGs), which are the central component of intracellular antiviral innate
      immunity. Inefficient induction of ISGs contributes to poor control and
      persistence of hepatitis C virus infection. Therefore, further understanding of
      the hepatocytic ISG regulation machinery will guide us to an improved management
      strategy against hepatitis C virus infection. In this study, comprehensive genome
      wide, high-throughput cDNA screening for genes regulating ISG expression
      identified a tyrosine kinase nonreceptor 1 (TNK1) as a unique player in the ISG
      induction pathway. The immune-modulatory function of TNK1 has never been studied,
      and this study characterizes its significance in antiviral innate immunity. TNK1
      is abundantly expressed in hepatocytes and maintains basal ISG expression. More
      importantly, TNK1 plays a critical role in type I IFN-mediated ISG induction. We
      discovered that the activated IFN receptor complex recruits TNK1 from the
      cytoplasm. TNK1 is then phosphorylated to enhance its kinase activity. The
      activated TNK1 potentiates JAK-STAT signaling through dual phosphorylation of
      STAT1 at tyrosine 701 and serine 727 amino acid positions. Our loss-of-function
      approach demonstrated that TNK1 governs a cluster of ISG expression that defines
      the TNK1 pathway effector genes. More importantly, TNK1 abundance is inversely
      correlated to viral replication efficiency and is also a determinant factor for
      the hepatocytic response to antiviral treatment. Taken together, our studies
      found a critical but unidentified integrated component of the IFN-JAK-STAT
      signaling cascade. 

PMID- 24449863
TI  - China's international trade and air pollution in the United States.
AB  - China is the world's largest emitter of anthropogenic air pollutants, and
      measurable amounts of Chinese pollution are transported via the atmosphere to
      other countries, including the United States. However, a large fraction of
      Chinese emissions is due to manufacture of goods for foreign consumption. Here,
      we analyze the impacts of trade-related Chinese air pollutant emissions on the
      global atmospheric environment, linking an economic-emission analysis and
      atmospheric chemical transport modeling. We find that in 2006, 36% of
      anthropogenic sulfur dioxide, 27% of nitrogen oxides, 22% of carbon monoxide, and
      17% of black carbon emitted in China were associated with production of goods for
      export. For each of these pollutants, about 21% of export-related Chinese
      emissions were attributed to China-to-US export. Atmospheric modeling shows that
      transport of the export-related Chinese pollution contributed 3-10% of annual
      mean surface sulfate concentrations and 0.5-1.5% of ozone over the western United
      States in 2006. This Chinese pollution also resulted in one extra day or more of
      noncompliance with the US ozone standard in 2006 over the Los Angeles area and
      many regions in the eastern United States. On a daily basis, the export-related
      Chinese pollution contributed, at a maximum, 12-24% of sulfate concentrations
      over the western United States. As the United States outsourced manufacturing to
      China, sulfate pollution in 2006 increased in the western United States but
      decreased in the eastern United States, reflecting the competing effect between
      enhanced transport of Chinese pollution and reduced US emissions. Our findings
      are relevant to international efforts to reduce transboundary air pollution. 

PMID- 24449864
TI  - Differences in the right inferior longitudinal fasciculus but no general
      disruption of white matter tracts in children with autism spectrum disorder.
AB  - One of the most widely cited features of the neural phenotype of autism is
      reduced "integrity" of long-range white matter tracts, a claim based primarily on
      diffusion imaging studies. However, many prior studies have small sample sizes
      and/or fail to address differences in data quality between those with autism
      spectrum disorder (ASD) and typical participants, and there is little consensus
      on which tracts are affected. To overcome these problems, we scanned a large
      sample of children with autism (n = 52) and typically developing children (n =
      73). Data quality was variable, and worse in the ASD group, with some scans
      unusable because of head motion artifacts. When we follow standard data analysis
      practices (i.e., without matching head motion between groups), we replicate the
      finding of lower fractional anisotropy (FA) in multiple white matter tracts.
      However, when we carefully match data quality between groups, all these effects
      disappear except in one tract, the right inferior longitudinal fasciculus (ILF).
      Additional analyses showed the expected developmental increases in the FA of
      fiber tracts within ASD and typical groups individually, demonstrating that we
      had sufficient statistical power to detect known group differences. Our data
      challenge the widely claimed general disruption of white matter tracts in autism,
      instead implicating only one tract, the right ILF, in the ASD phenotype. 

PMID- 24449865
TI  - Development of pattern vision following early and extended blindness.
AB  - Visual plasticity peaks during early critical periods of normal visual
      development. Studies in animals and humans provide converging evidence that gains
      in visual function are minimal and deficits are most severe when visual
      deprivation persists beyond the critical period. Here we demonstrate visual
      development in a unique sample of patients who experienced extended early-onset
      blindness (beginning before 1 y of age and lasting 8-17 y) before removal of
      bilateral cataracts. These patients show surprising improvements in contrast
      sensitivity, an assay of basic spatial vision. We find that contrast sensitivity
      development is independent of the age of sight onset and that individual rates of
      improvement can exceed those exhibited by normally developing infants. These
      results reveal that the visual system can retain considerable plasticity, even
      after early blindness that extends beyond critical periods. 

PMID- 24449866
TI  - Comparison of the isomerization mechanisms of human melanopsin and invertebrate
      and vertebrate rhodopsins.
AB  - Comparative modeling and ab initio multiconfigurational quantum chemistry are
      combined to investigate the reactivity of the human nonvisual photoreceptor
      melanopsin. It is found that both the thermal and photochemical isomerization of
      the melanopsin 11-cis retinal chromophore occur via a space-saving mechanism
      involving the unidirectional, counterclockwise twisting of the =C11H-C12H= moiety
      with respect to its Lys340-linked frame as proposed by Warshel for visual
      pigments [Warshel A (1976) Nature 260(5553):679-683]. A comparison with the
      mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual
      photoreceptors shows that such a mechanism is not affected by the diversity of
      the three chromophore cavities. Despite such invariance, trajectory computations
      indicate that although all receptors display less than 100 fs excited state
      dynamics, human melanopsin decays from the excited state ~40 fs earlier than
      bovine rhodopsin. Some diversity is also found in the energy barriers controlling
      thermal isomerization. Human melanopsin features the highest computed barrier
      which appears to be ~2.5 kcal mol(-1) higher than that of bovine rhodopsin. When
      assuming the validity of both the reaction speed/quantum yield correlation
      discussed by Warshel, Mathies and coworkers [Weiss RM, Warshel A (1979) J Am Chem
      Soc 101:6131-6133; Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) Science
      254(5030):412-415] and of a relationship between thermal isomerization rate and
      thermal activation of the photocycle, melanopsin turns out to be a highly
      sensitive pigment consistent with the low number of melanopsin-containing cells
      found in the retina and with the extraretina location of melanopsin in
      nonmammalian vertebrates. 

PMID- 24449867
TI  - Role of clusters in nonclassical nucleation and growth of protein crystals.
AB  - The development of multistep nucleation theory has spurred on experimentalists to
      find intermediate metastable states that are relevant to the solidification
      pathway of the molecule under interest. A great deal of studies focused on
      characterizing the so-called "precritical clusters" that may arise in the
      precipitation process. However, in macromolecular systems, the role that these
      clusters might play in the nucleation process and in the second stage of the
      precipitation process, i.e., growth, remains to a great extent unknown.
      Therefore, using biological macromolecules as a model system, we have studied the
      mesoscopic intermediate, the solid end state, and the relationship that exists
      between them. We present experimental evidence that these clusters are liquid
      like and stable with respect to the parent liquid and metastable compared with
      the emerging crystalline phase. The presence of these clusters in the bulk liquid
      is associated with a nonclassical mechanism of crystal growth and can trigger a
      self-purifying cascade of impurity-poisoned crystal surfaces. These observations
      demonstrate that there exists a nontrivial connection between the growth of the
      macroscopic crystalline phase and the mesoscopic intermediate which should not be
      ignored. On the other hand, our experimental data also show that clusters
      existing in protein solutions can significantly increase the nucleation rate and
      therefore play a relevant role in the nucleation process. 

PMID- 24449868
TI  - Differential expression of estrogen receptor alpha, beta1, and beta2 in lobular
      and ductal breast cancer.
AB  - The role of estrogen receptor (ER) alpha as a target in treatment of breast
      cancer is clear, but those of ERbeta1 and ERbeta2 in the breast remain unclear.
      We have examined expression of all three receptors in surgically excised breast
      samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese
      study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College.
      Samples contained normal areas, areas of hyperplasia, and in situ and invasive
      cancer. In the normal areas, ERalpha was expressed in not more than 10% of
      epithelium, whereas approximately 80% of epithelial cells expressed ERbeta. We
      found that whereas ductal cancer is a highly proliferative, ERalpha-positive,
      ERbeta-negative disease, lobular cancer expresses both ERalpha and ERbeta but
      with very few Ki67-positive cells. ERbeta2 was expressed in 32% of the ductal
      cancers, of which 83% were postmenopausal. In all ERbeta2-positive cancers the
      interductal space was filled with dense collagen, and cell nuclei expressed
      hypoxia-inducible factor 1alpha. ERbeta2 expression was not confined to malignant
      cells but was strong in stromal, immune, and endothelial cells. In most of the
      high-grade invasive ductal cancers neither ERalpha nor ERbeta was expressed, but
      in the high-grade lobular cancer ERbeta was lost and ERalpha and Ki67 expression
      were abundant. The data show a clear difference in ER expression between lobular
      and ductal breast cancer and suggest (i) that tamoxifen may be more effective in
      late than in early lobular cancer and (ii) a potential role for ERbeta agonists
      in preventing in situ ductal cancers from becoming invasive. 

PMID- 24449869
TI  - Detection of solar wind-produced water in irradiated rims on silicate minerals.
AB  - The solar wind (SW), composed of predominantly ~1-keV H(+) ions, produces
      amorphous rims up to ~150 nm thick on the surfaces of minerals exposed in space.
      Silicates with amorphous rims are observed on interplanetary dust particles and
      on lunar and asteroid soil regolith grains. Implanted H(+) may react with oxygen
      in the minerals to form trace amounts of hydroxyl (-OH) and/or water (H2O).
      Previous studies have detected hydroxyl in lunar soils, but its chemical state,
      physical location in the soils, and source(s) are debated. If -OH or H2O is
      generated in rims on silicate grains, there are important implications for the
      origins of water in the solar system and other astrophysical environments. By
      exploiting the high spatial resolution of transmission electron microscopy and
      valence electron energy-loss spectroscopy, we detect water sealed in vesicles
      within amorphous rims produced by SW irradiation of silicate mineral grains on
      the exterior surfaces of interplanetary dust particles. Our findings establish
      that water is a byproduct of SW space weathering. We conclude, on the basis of
      the pervasiveness of the SW and silicate materials, that the production of
      radiolytic SW water on airless bodies is a ubiquitous process throughout the
      solar system. 

PMID- 24449871
TI  - Compressed plane waves yield a compactly supported multiresolution basis for the
      Laplace operator.
AB  - This paper describes an L1 regularized variational framework for developing a
      spatially localized basis, compressed plane waves, that spans the eigenspace of a
      differential operator, for instance, the Laplace operator. Our approach
      generalizes the concept of plane waves to an orthogonal real-space basis with
      multiresolution capabilities.

PMID- 24449870
TI  - Paternally induced transgenerational inheritance of susceptibility to diabetes in
      mammals.
AB  - The global prevalence of prediabetes and type 2 diabetes (T2D) is increasing, and
      it is contributing to the susceptibility to diabetes and its related epidemic in
      offspring. Although the impacts of paternal impaired fasting blood glucose and
      glucose intolerance on the metabolism of offspring have been well established,
      the exact molecular and mechanistic basis that mediates these impacts remains
      largely unclear. Here we show that paternal prediabetes increases the
      susceptibility to diabetes in offspring through gametic epigenetic alterations.
      In our findings, paternal prediabetes led to glucose intolerance and insulin
      resistance in offspring. Relative to controls, offspring of prediabetic fathers
      exhibited altered gene expression patterns in the pancreatic islets, with down
      regulation of several genes involved in glucose metabolism and insulin signaling
      pathways. Epigenomic profiling of offspring pancreatic islets revealed numerous
      changes in cytosine methylation depending on paternal prediabetes, including
      reproducible changes in methylation over several insulin signaling genes.
      Paternal prediabetes altered overall methylome patterns in sperm, with a large
      portion of differentially methylated genes overlapping with that of pancreatic
      islets in offspring. Our study uniquely revealed that prediabetes can be
      inherited transgenerationally through the mammalian germ line by an epigenetic
      mechanism. 

PMID- 24449873
TI  - Small business activity does not measure entrepreneurship.
AB  - Entrepreneurship policy mainly aims to promote innovative Schumpeterian
      entrepreneurship. However, the rate of entrepreneurship is commonly proxied using
      quantity-based metrics, such as small business activity, the self-employment
      rate, or the number of startups. We argue that those metrics give rise to
      misleading inferences regarding high-impact Schumpeterian entrepreneurship. To
      unambiguously identify high-impact entrepreneurs we focus on self-made
      billionaires (in US dollars) who appear on Forbes Magazine's list and who became
      wealthy by founding new firms. We identify 996 such billionaire entrepreneurs in
      50 countries in 1996-2010, a systematic cross-country study of billionaire
      entrepreneurs. The rate of billionaire entrepreneurs correlates negatively with
      self-employment, small business ownership, and firm startup rates. Countries with
      higher income, higher trust, lower taxes, more venture capital investment, and
      lower regulatory burdens have higher billionaire entrepreneurship rates but less
      self-employment. Despite its limitations, the number of billionaire entrepreneurs
      appears to be a plausible cross-country measure of Schumpeterian
      entrepreneurship. 

PMID- 24449872
TI  - Elevated expression of TANK-binding kinase 1 enhances tamoxifen resistance in
      breast cancer.
AB  - Resistance to antiestrogens is one of the major challenges in breast cancer
      treatment. Although phosphorylation of estrogen receptor alpha (ERalpha) is an
      important factor in endocrine resistance, the contributions of specific kinases
      in endocrine resistance are still not fully understood. Here, we report that an
      important innate immune response kinase, the IkappaB kinase-related TANK-binding
      kinase 1 (TBK1), is a crucial determinant of resistance to tamoxifen therapies.
      We show that TBK1 increases ERalpha transcriptional activity through
      phosphorylation modification of ERalpha at the Ser-305 site. Ectopic TBK1
      expression impairs the responsiveness of breast cancer cells to tamoxifen. By
      studying the specimens from patients with breast cancer, we find a strong
      positive correlation of TBK1 with ERalpha, ERalpha Ser-305, and cyclin D1.
      Notably, patients with tumors highly expressing TBK1 respond poorly to tamoxifen
      treatment and show high potential for relapse. Therefore, our findings suggest
      that TBK1 contributes to tamoxifen resistance in breast cancer via
      phosphorylation modification of ERalpha. 

PMID- 24449874
TI  - Decision-related pupil dilation reflects upcoming choice and individual bias.
AB  - A number of studies have shown that pupil size increases transiently during
      effortful decisions. These decision-related changes in pupil size are mediated by
      central neuromodulatory systems, which also influence the internal state of brain
      regions engaged in decision making. It has been proposed that pupil-linked
      neuromodulatory systems are activated by the termination of decision processes,
      and, consequently, that these systems primarily affect the postdecisional brain
      state. Here, we present pupil results that run contrary to this proposal,
      suggesting an important intradecisional role. We measured pupil size while
      subjects formed protracted decisions about the presence or absence ("yes" vs.
      "no") of a visual contrast signal embedded in dynamic noise. Linear systems
      analysis revealed that the pupil was significantly driven by a sustained input
      throughout the course of the decision formation. This sustained component was
      larger than the transient component during the final choice (indicated by button
      press). The overall amplitude of pupil dilation during decision formation was
      bigger before yes than no choices, irrespective of the physical presence of the
      target signal. Remarkably, the magnitude of this pupil choice effect (yes > no)
      reflected the individual criterion: it was strongest in conservative subjects
      choosing yes against their bias. We conclude that the central neuromodulatory
      systems controlling pupil size are continuously engaged during decision formation
      in a way that reveals how the upcoming choice relates to the decision maker's
      attitude. Changes in brain state seem to interact with biased decision making in
      the face of uncertainty. 

PMID- 24449875
TI  - Quantifying the distribution of nanodiamonds in pre-Younger Dryas to recent age
      deposits along Bull Creek, Oklahoma panhandle, USA.
AB  - High levels of nanodiamonds (nds) have been used to support the transformative
      hypothesis that an extraterrestrial (ET) event (comet explosion) triggered
      Younger Dryas changes in temperature, flora and fauna assemblages, and human
      adaptations [Firestone RB, et al. (2007) Proc Natl Acad Sci USA 104(41):16016
      16021]. We evaluate this hypothesis by establishing the distribution of nds
      within the Bull Creek drainage of the Beaver River basin in the Oklahoma
      panhandle. The earlier report of an abundance spike of nds in the Bull Creek I
      Younger Dryas boundary soil is confirmed, although no pure cubic diamonds were
      identified. The lack of hexagonal nds suggests Bull Creek I is not near any
      impact site. Potential hexagonal nds at Bull Creek were found to be more
      consistent with graphene/graphane. An additional nd spike is found in deposits of
      late Holocene through the modern age, indicating nds are not unique to the
      Younger Dryas boundary. Nd distributions do not correlate with depositional
      environment, pedogenesis, climate perturbations, periods of surface stability, or
      cultural activity. 

PMID- 24449876
TI  - Mistimed sleep disrupts circadian regulation of the human transcriptome.
AB  - Circadian organization of the mammalian transcriptome is achieved by rhythmic
      recruitment of key modifiers of chromatin structure and transcriptional and
      translational processes. These rhythmic processes, together with
      posttranslational modification, constitute circadian oscillators in the brain and
      peripheral tissues, which drive rhythms in physiology and behavior, including the
      sleep-wake cycle. In humans, sleep is normally timed to occur during the
      biological night, when body temperature is low and melatonin is synthesized.
      Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in
      shift work and jet lag, is associated with disruption of rhythmicity in
      physiology and endocrinology. However, to what extent mistimed sleep affects the
      molecular regulators of circadian rhythmicity remains to be established. Here, we
      show that mistimed sleep leads to a reduction of rhythmic transcripts in the
      human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony
      of sleep and centrally driven circadian rhythms. Transcripts affected are key
      regulators of gene expression, including those associated with chromatin
      modification (methylases and acetylases), transcription (RNA polymerase II),
      translation (ribosomal proteins, initiation, and elongation factors), temperature
      regulated transcription (cold inducible RNA-binding proteins), and core clock
      genes including CLOCK and ARNTL (BMAL1). We also estimated the separate
      contribution of sleep and circadian rhythmicity and found that the sleep-wake
      cycle coordinates the timing of transcription and translation in particular. The
      data show that mistimed sleep affects molecular processes at the core of
      circadian rhythm generation and imply that appropriate timing of sleep
      contributes significantly to the overall temporal organization of the human
      transcriptome. 

PMID- 24449877
TI  - CLE-CLAVATA1 peptide-receptor signaling module regulates the expansion of plant
      root systems in a nitrogen-dependent manner.
AB  - Morphological plasticity of root systems is critically important for plant
      survival because it allows plants to optimize their capacity to take up water and
      nutrients from the soil environment. Here we show that a signaling module
      composed of nitrogen (N)-responsive CLE (CLAVATA3/ESR-related) peptides and the
      CLAVATA1 (CLV1) leucine-rich repeat receptor-like kinase is expressed in the root
      vasculature in Arabidopsis thaliana and plays a crucial role in regulating the
      expansion of the root system under N-deficient conditions. CLE1, -3, -4, and -7
      were induced by N deficiency in roots, predominantly expressed in root pericycle
      cells, and their overexpression repressed the growth of lateral root primordia
      and their emergence from the primary root. In contrast, clv1 mutants showed
      progressive outgrowth of lateral root primordia into lateral roots under N
      deficient conditions. The clv1 phenotype was reverted by introducing a CLV1
      promoter-driven CLV1:GFP construct producing CLV1:GFP fusion proteins in phloem
      companion cells of roots. The overaccumulation of CLE2, -3, -4, and -7 in clv1
      mutants suggested the amplitude of the CLE peptide signals being feedback
      regulated by CLV1. When CLE3 was overexpressed under its own promoter in wild
      type plants, the length of lateral roots was negatively correlated with
      increasing CLE3 mRNA levels; however, this inhibitory action of CLE3 was
      abrogated in the clv1 mutant background. Our findings identify the N-responsive
      CLE-CLV1 signaling module as an essential mechanism restrictively controlling the
      expansion of the lateral root system in N-deficient environments. 

PMID- 24449878
TI  - Toward rationally redesigning bacterial two-component signaling systems using
      coevolutionary information.
AB  - A challenge in molecular biology is to distinguish the key subset of residues
      that allow two-component signaling (TCS) proteins to recognize their correct
      signaling partner such that they can transiently bind and transfer signal, i.e.,
      phosphoryl group. Detailed knowledge of this information would allow one to
      search sequence space for mutations that can be used to systematically tune the
      signal transmission between TCS partners as well as potentially encode a TCS
      protein to preferentially transfer signals to a nonpartner. Motivated by the
      notion that this detailed information is found in sequence data, we explore the
      sequence coevolution between signaling partners to better understand how
      mutations can positively or negatively alter their ability to transfer signal.
      Using direct coupling analysis for determining evolutionarily conserved protein
      protein interactions, we apply a metric called the direct information score to
      quantify mutational changes in the interaction between TCS proteins and
      demonstrate that it accurately correlates with experimental mutagenesis studies
      probing the mutational change in measured in vitro phosphotransfer. Furthermore,
      by subtracting from our metric an appropriate null model corresponding to
      generic, conserved features in TCS signaling pairs, we can isolate the
      determinants that give rise to interaction specificity and recognition, which are
      variable among different TCS partners. Our methodology forms a potential
      framework for the rational design of TCS systems by allowing one to quickly
      search sequence space for mutations or even entirely new sequences that can
      increase or decrease our metric, as a proxy for increasing or decreasing
      phosphotransfer ability between TCS proteins. 

PMID- 24449879
TI  - Acoustic droplet vaporization is initiated by superharmonic focusing.
AB  - Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon
      have the potential to be a highly efficient system for local drug delivery,
      embolotherapy, or for tumor imaging. The physical mechanisms underlying the
      acoustic activation of these phase-change emulsions into a bubbly dispersion,
      termed acoustic droplet vaporization, have not been well understood. The droplets
      have a very high activation threshold; its frequency dependence does not comply
      with homogeneous nucleation theory and localized nucleation spots have been
      observed. Here we show that acoustic droplet vaporization is initiated by a
      combination of two phenomena: highly nonlinear distortion of the acoustic wave
      before it hits the droplet and focusing of the distorted wave by the droplet
      itself. At high excitation pressures, nonlinear distortion causes significant
      superharmonics with wavelengths of the order of the droplet size. These
      superharmonics strongly contribute to the focusing effect; therefore, the
      proposed mechanism also explains the observed pressure thresholding effect. Our
      interpretation is validated with experimental data captured with an ultrahigh
      speed camera on the positions of the nucleation spots, where we find excellent
      agreement with the theoretical prediction. Moreover, the presented mechanism
      explains the hitherto counterintuitive dependence of the nucleation threshold on
      the ultrasound frequency. The physical insight allows for the optimization of
      acoustic droplet vaporization for therapeutic applications, in particular with
      respect to the acoustic pressures required for activation, thereby minimizing the
      negative bioeffects associated with the use of high-intensity ultrasound. 

PMID- 24449880
TI  - Chiral symmetry breaking and surface faceting in chromonic liquid crystal
      droplets with giant elastic anisotropy.
AB  - Confined liquid crystals (LC) provide a unique platform for technological
      applications and for the study of LC properties, such as bulk elasticity, surface
      anchoring, and topological defects. In this work, lyotropic chromonic liquid
      crystals (LCLCs) are confined in spherical droplets, and their director
      configurations are investigated as a function of mesogen concentration using
      bright-field and polarized optical microscopy. Because of the unusually small
      twist elastic modulus of the nematic phase of LCLCs, droplets of this phase
      exhibit a twisted bipolar configuration with remarkably large chiral symmetry
      breaking. Further, the hexagonal ordering of columns and the resultant strong
      suppression of twist and splay but not bend deformation in the columnar phase,
      cause droplets of this phase to adopt a concentric director configuration around
      a central bend disclination line and, at sufficiently high mesogen concentration,
      to exhibit surface faceting. Observations of director configurations are
      consistent with Jones matrix calculations and are understood theoretically to be
      a result of the giant elastic anisotropy of LCLCs. 

PMID- 24449882
TI  - ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism
      to support biosynthesis in human cytomegalovirus-infected cells.
AB  - Carbohydrate-response element binding protein (ChREBP) plays a key role in
      regulating glucose metabolism and de novo lipogenesis in metabolic tissues and
      cancer cells. Here we report that ChREBP is also a critical regulator of the
      metabolic alterations induced during human cytomegalovirus (HCMV) infection. The
      expression of both ChREBP-alpha and ChREBP-beta is robustly induced in HCMV
      infected human fibroblasts; this induction is required for efficient HCMV
      infection. Depletion of ChREBP in HCMV-infected cells results in reduction of
      HCMV-induced glucose transporter 4 and glucose transporter 2 expression, leading
      to inhibition of glucose uptake, lactate production, nucleotide biosynthesis, and
      NADPH generation. We previously reported that HCMV infection induces lipogenesis
      through the activation of sterol regulatory element binding protein 1, which is
      mediated by the induction of PKR-like endoplasmic reticulum kinase. Data from the
      present study show that HCMV-induced lipogenesis is also controlled by the
      induction of ChREBP, in a second mechanism involved in the regulation of HCMV
      induced de novo lipogenesis. These results suggest that ChREBP plays a key role
      in reprogramming glucose and lipid metabolism in HCMV infection. 

PMID- 24449881
TI  - PhoPQ regulates acidic glycerophospholipid content of the Salmonella Typhimurium
      outer membrane.
AB  - Gram-negative bacteria have two lipid membranes separated by a periplasmic space
      containing peptidoglycan. The surface bilayer, or outer membrane (OM), provides a
      barrier to toxic molecules, including host cationic antimicrobial peptides
      (CAMPs). The OM comprises an outer leaflet of lipid A, the bioactive component of
      lipopolysaccharide (LPS), and an inner leaflet of glycerophospholipids (GPLs).
      The structure of lipid A is environmentally regulated in a manner that can
      promote bacterial infection by increasing bacterial resistance to CAMP and
      reducing LPS recognition by the innate immune system. The gastrointestinal
      pathogen, Salmonella Typhimurium, responds to acidic pH and CAMP through the
      PhoPQ two-component regulatory system, which stimulates lipid A remodeling, CAMP
      resistance, and intracellular survival within acidified phagosomes. Work here
      demonstrates that, in addition to regulating lipid A structure, the S.
      Typhimurium PhoPQ virulence regulators also regulate acidic GPL by increasing the
      levels of cardiolipins and palmitoylated acylphosphatidylglycerols within the OM.
      Triacylated palmitoyl-PG species were diminished in strains deleted for the PhoPQ
      regulated OM lipid A palmitoyltransferase enzyme, PagP. Purified PagP transferred
      palmitate to PG consistent with PagP acylation of both lipid A and PG within the
      OM. Therefore, PhoPQ coordinately regulates OM acidic GPL with lipid A structure,
      suggesting that GPLs cooperate with lipid A to form an OM barrier critical for
      CAMP resistance and intracellular survival of S. Typhimurium. 

PMID- 24449884
TI  - Different modes of endothelial-smooth muscle cell interaction elicit differential
      beta-catenin phosphorylations and endothelial functions.
AB  - beta-Catenin phosphorylation plays important roles in modulating its functions,
      but the effects of different phosphorylated forms of beta-catenin in response to
      heterocellular interaction are unclear. Here we investigated whether distinct
      modes of phosphorylation on beta-catenin could be triggered through
      heterocellular interactions between endothelial cells (ECs) and smooth muscle
      cells (SMCs), and the consequent modulation of EC functions. ECs were cocultured
      with SMCs to initiate direct contact and paracrine interaction. EC-SMC coculture
      induced EC beta-catenin phosphorylations simultaneously at tyrosine 142 (Tyr142)
      and serine 45/threonine 41 (Ser45/Thr41) at the cytoplasm/nuclei and the
      membrane, respectively. Treating ECs with SMC-conditional medium induced beta
      catenin phosphorylation only at Ser45/Thr41. These findings indicate that
      different phosphorylation effects of EC-SMC coculture were induced through
      heterocellular direct contact and paracrine effects, respectively. Using specific
      blocking peptides, antagonists, and siRNAs, we found that the beta-catenin Tyr142
      phosphorylation was mediated by connexin 43/Fer and that the beta-catenin
      Ser45/Thr41-phosphorylation was mediated by SMC-released bone morphogenetic
      proteins through VE-cadherin and bone morphogenetic protein receptor-II/Smad5.
      Transfecting ECs with beta-catenin-Tyr142 or -Ser45 mutants showed that these two
      phosphorylated forms of beta-catenin modulate differential EC function: The
      Tyr142-phosphorylated beta-catenin stimulates vascular cell-adhesion molecule-1
      expression to increase EC-monocytic adhesion, but the Ser45/Thr41-phosphorylated
      beta-catenin attenuates VE-cadherin-dependent junction structures to increase EC
      permeability. Our findings provide new insights into the understanding of
      regulatory complexities of distinct modes of beta-catenin phosphorylations under
      EC-SMC interactions and suggest that different phosphorylated forms of beta
      catenin play important roles in modulating vascular pathophysiology through
      different heterocellular interactions. 

PMID- 24449885
TI  - Empirical prediction of genomic susceptibilities for multiple cancer classes.
AB  - An empirical approach is presented for predicting the genomic susceptibility of
      an individual to the most likely one among nine traits, consisting of eight major
      cancer classes plus a healthy trait. We use four prediction methods by applying
      two supervised learning algorithms to two different descriptors of common genomic
      variations (the profiles of genotypes of SNPs and SNP syntaxes with low P values
      or low frequencies) of each individual genome from normal cells. All four methods
      made correct predictions substantially better than random predictions for most
      cancer classes, but not for some others. A combination of the four results using
      Bayesian inference better predicted overall than any individual method. The
      multiclass accuracy of the combined prediction ranges from 33% to 56% depending
      on cancer classes of testing sets, compared with 11% for a random prediction
      among nine traits. Despite limited SNP data available and the absence of rare
      SNPs in public databases, at present, the results suggest that the framework of
      this approach or its improvement can predict cancer susceptibility with
      probability estimates useful for making health decisions for individuals or for a
      population. 

PMID- 24449886
TI  - Guest-host interactions of a rigid organic molecule in porous silica frameworks.
AB  - Molecular-level interactions at organic-inorganic interfaces play crucial roles
      in many fields including catalysis, drug delivery, and geological mineral
      precipitation in the presence of organic matter. To seek insights into organic
      inorganic interactions in porous framework materials, we investigated the phase
      evolution and energetics of confinement of a rigid organic guest, N,N,N-trimethyl
      1-adamantammonium iodide (TMAAI), in inorganic porous silica frameworks (SSZ-24,
      MCM-41, and SBA-15) as a function of pore size (0.8 nm to 20.0 nm). We used
      hydrofluoric acid solution calorimetry to obtain the enthalpies of interaction
      between silica framework materials and TMAAI, and the values range from -56 to 
      177 kJ per mole of TMAAI. The phase evolution as a function of pore size was
      investigated by X-ray diffraction, IR, thermogravimetric differential scanning
      calorimetry, and solid-state NMR. The results suggest the existence of three
      types of inclusion depending on the pore size of the framework: single-molecule
      confinement in a small pore, multiple-molecule confinement/adsorption of an
      amorphous and possibly mobile assemblage of molecules near the pore walls, and
      nanocrystal confinement in the pore interior. These changes in structure probably
      represent equilibrium and minimize the free energy of the system for each pore
      size, as indicated by trends in the enthalpy of interaction and differential
      scanning calorimetry profiles, as well as the reversible changes in structure and
      mobility seen by variable temperature NMR. 

PMID- 24449887
TI  - Self-replicating colloidal clusters.
AB  - We construct schemes for self-replicating clusters of spherical particles,
      validated with computer simulations in a finite-temperature heat bath. Each
      particle has stickers uniformly distributed over its surface, and the rules for
      self-replication are encoded into the specificity and strength of interactions.
      Geometrical constraints imply that a compact cluster can copy itself only with
      help of a catalyst, a smaller cluster that increases the surface area to form a
      template. Replication efficiency requires optimizing interaction energies to
      destabilize all kinetic traps along the reaction pathway, as well as initiating a
      trigger event that specifies when the new cluster disassociates from its parent.
      Although there is a reasonably wide parameter range for self-replication, there
      is a subtle balance between the speed of the reaction, and the error rate. As a
      proof of principle, we construct interactions that self-replicate an octahedron,
      requiring a two-particle dimer for a catalyst. The resulting self-replication
      scheme is a hypercycle, and computer simulations confirm the exponential growth
      of both octahedron and catalyst replicas. 

PMID- 24449888
TI  - Induced multipotency in adult keratinocytes through down-regulation of DeltaNp63
      or DGCR8.
AB  - The roles of microRNAs (miRNAs) and the miRNA processing machinery in the
      regulation of stem cell biology are not well understood. Here, we show that the
      p53 family member and p63 isoform, DeltaNp63, is a transcriptional activator of a
      cofactor critical for miRNA processing (DGCR8). This regulation gives rise to a
      unique miRNA signature resulting in reprogramming cells to multipotency.
      Strikingly, DeltaNp63(-/-) epidermal cells display profound defects in terminal
      differentiation and express a subset of markers and miRNAs present in embryonic
      stem cells and fibroblasts induced to pluripotency using Yamanaka factors.
      Moreover, DeltaNp63(-/-) epidermal cells transduced with an inducible DGCR8
      plasmid can differentiate into multiple cell fates in vitro and in vivo. We found
      that human primary keratinocytes depleted of DeltaNp63 or DGCR8 can be
      reprogrammed in 6 d and express a unique miRNA and gene expression signature that
      is similar but not identical to human induced pluripotent stem cells. Our data
      reveal a role for DeltaNp63 in the transcriptional regulation of DGCR8 to
      reprogram adult somatic cells into multipotent stem cells. 

PMID- 24449889
TI  - Kinetochore assembly and heterochromatin formation occur autonomously in
      Schizosaccharomyces pombe.
AB  - Kinetochores in multicellular eukaryotes are usually associated with
      heterochromatin. Whether this heterochromatin simply promotes the cohesion
      necessary for accurate chromosome segregation at cell division or whether it also
      has a role in kinetochore assembly is unclear. Schizosaccharomyces pombe is an
      important experimental system for investigating centromere function, but all of
      the previous work with this species has exploited a single strain or its
      derivatives. The laboratory strain and most other S. pombe strains contain three
      chromosomes, but one recently discovered strain, CBS 2777, contains four. We show
      that the genome of CBS 2777 is related to that of the laboratory strain by a
      complex chromosome rearrangement. As a result, two of the kinetochores in CBS
      2777 contain the central core sequences present in the laboratory strain
      centromeres, but lack adjacent heterochromatin. The closest block of
      heterochromatin to these rearranged kinetochores is ~100 kb away at new
      telomeres. Despite lacking large amounts of adjacent heterochromatin, the
      rearranged kinetochores bind CENP-A(Cnp1) and CENP-C(Cnp3) in similar quantities
      and with similar specificities as those of the laboratory strain. The simplest
      interpretation of this result is that constitutive kinetochore assembly and
      heterochromatin formation occur autonomously. 

PMID- 24449890
TI  - Molecular indexing enables quantitative targeted RNA sequencing and reveals poor
      efficiencies in standard library preparations.
AB  - We present a simple molecular indexing method for quantitative targeted RNA
      sequencing, in which mRNAs of interest are selectively captured from complex cDNA
      libraries and sequenced to determine their absolute concentrations. cDNA
      fragments are individually labeled so that each molecule can be tracked from the
      original sample through the library preparation and sequencing process. Multiple
      copies of cDNA fragments of identical sequence become distinct through labeling,
      and replicate clones created during PCR amplification steps can be identified and
      assigned to their distinct parent molecules. Selective capture enables efficient
      use of sequencing for deep sampling and for the absolute quantitation of rare or
      transient transcripts that would otherwise escape detection by standard
      sequencing methods. We have also constructed a set of synthetic barcoded RNA
      molecules, which can be introduced as controls into the sample preparation mix
      and used to monitor the efficiency of library construction. The quantitative
      targeted sequencing revealed extremely low efficiency in standard library
      preparations, which were further confirmed by using synthetic barcoded RNA
      molecules. This finding shows that standard library preparation methods result in
      the loss of rare transcripts and highlights the need for monitoring library
      efficiency and for developing more efficient sample preparation methods. 

PMID- 24449891
TI  - Artificial riboswitches for gene expression and replication control of DNA and
      RNA viruses.
AB  - Aptazymes are small, ligand-dependent self-cleaving ribozymes that function
      independently of transcription factors and can be customized for induction by
      various small molecules. Here, we introduce these artificial riboswitches for
      regulation of DNA and RNA viruses. We hypothesize that they represent universally
      applicable tools for studying viral gene functions and for applications as a
      safety switch for oncolytic and live vaccine viruses. Our study shows that the
      insertion of artificial aptazymes into the adenoviral immediate early gene E1A
      enables small-molecule-triggered, dose-dependent inhibition of gene expression.
      Aptazyme-mediated shutdown of E1A expression translates into inhibition of
      adenoviral genome replication, infectious particle production, and
      cytotoxicity/oncolysis. These results provide proof of concept for the aptazyme
      approach for effective control of biological outcomes in eukaryotic systems,
      specifically in virus infections. Importantly, we also demonstrate aptazyme
      dependent regulation of measles virus fusion protein expression, translating into
      potent reduction of progeny infectivity and virus spread. This not only
      establishes functionality of aptazymes in fully cytoplasmic genetic systems, but
      also implicates general feasibility of this strategy for application in viruses
      with either DNA or RNA genomes. Our study implies that gene regulation by
      artificial riboswitches may be an appealing alternative to Tet- and other protein
      dependent gene regulation systems, based on their small size, RNA-intrinsic mode
      of action, and flexibility of the inducing molecule. Future applications range
      from gene analysis in basic research to medicine, for example as a safety switch
      for new generations of efficiency-enhanced oncolytic viruses. 

PMID- 24449893
TI  - Digital microfluidic assay for protein detection.
AB  - Global studies of the human proteome have revealed a plethora of putative protein
      biomarkers. However, their application for early disease detection remains at a
      standstill without suitable methods to realize their utility in the clinical
      setting. There thus continues to be tremendous interest in developing new
      technology for sensitive protein detection that is both low in cost and carries a
      small footprint to be able to be used at the point of care. The current gold
      standard method for protein biomarker detection is the ELISA, which measures
      protein abundance using bulky fluorescent scanners that lack portability. Here,
      we present a digital microfluidic platform for protein biomarker detection that
      is low in cost compared with standard optical detection methods, without any
      compromise in sensitivity. This platform furthermore makes use of simple
      electronics, enabling its translation into a portable handheld device, and has
      been developed in a manner that can easily be adapted to assay different types of
      proteomic biomarkers. We demonstrate its utility in quantifying not only protein
      abundance, but also activity. Interleukin-6 abundance could be assayed from
      concentrations as low as 50 pM (an order of magnitude lower than that detectable
      by a comparable laboratory designed ELISA) using less than 5 MUL of sample, and
      Abelson tyrosine kinase activity was detectable in samples containing 100 pM of
      kinase. 

PMID- 24449892
TI  - TAp73 is required for spermatogenesis and the maintenance of male fertility.
AB  - The generation of viable sperm proceeds through a series of coordinated steps,
      including germ cell self-renewal, meiotic recombination, and terminal
      differentiation into functional spermatozoa. The p53 family of transcription
      factors, including p53, p63, and p73, are critical for many physiological
      processes, including female fertility, but little is known about their functions
      in spermatogenesis. Here, we report that deficiency of the TAp73 isoform, but not
      p53 or DeltaNp73, results in male infertility because of severe impairment of
      spermatogenesis. Mice lacking TAp73 exhibited increased DNA damage and cell death
      in spermatogonia, disorganized apical ectoplasmic specialization, malformed
      spermatids, and marked hyperspermia. We demonstrated that TAp73 regulates the
      mRNA levels of crucial genes involved in germ stem/progenitor cells (CDKN2B),
      spermatid maturation/spermiogenesis (metalloproteinase and serine proteinase
      inhibitors), and steroidogenesis (CYP21A2 and progesterone receptor). These
      alterations of testicular histology and gene expression patterns were specific to
      TAp73 null mice and not features of mice lacking p53. Our work provides
      previously unidentified in vivo evidence that TAp73 has a unique role in
      spermatogenesis that ensures the maintenance of mitotic cells and normal
      spermiogenesis. These results may have implications for the diagnosis and
      management of human male infertility. 

PMID- 24449895
TI  - Genetic predisposition of behavioral response.

PMID- 24449894
TI  - CRL4-like Clr4 complex in Schizosaccharomyces pombe depends on an exposed surface
      of Dos1 for heterochromatin silencing.
AB  - Repressive histone H3 lysine 9 methylation (H3K9me) and its recognition by HP1
      proteins are necessary for pericentromeric heterochromatin formation. In
      Schizosaccharomyces pombe, H3K9me deposition depends on the RNAi pathway. Cryptic
      loci regulator 4 (Clr4), the only known H3K9 methyltransferase in this organism,
      is a subunit of the Clr4 methyltransferase complex (CLRC), whose composition is
      reminiscent of a CRL4 type cullin-RING ubiquitin ligase (CRL) including its
      cullin Cul4, the RING-box protein Pip1, the DNA damage binding protein 1 homolog
      Rik1, and the DCAF-like protein delocalization of Swi6 1 (Dos1). Dos2 and Stc1
      have been proposed to be part of the complex but do not bear similarity to
      canonical ubiquitin ligase components. CLRC is an active E3 ligase in vitro, and
      this activity is necessary for heterochromatin assembly in vivo. The similarity
      between CLRC and the CRLs suggests that the WD repeat protein Dos1 will act to
      mediate target recognition and substrate specificity for CLRC. Here, we present a
      pairwise interaction screen that confirms a CRL4-like subunit arrangement and
      further identifies Dos2 as a central component of the complex and recruiter of
      Stc1. We determined the crystal structure of the Dos1 WD repeat domain, revealing
      an eight-bladed beta-propeller fold. Functional mapping of the putative target
      binding surface of Dos1 identifies key residues required for heterochromatic
      silencing, consistent with Dos1's role as the specificity factor for the E3
      ubiquitin ligase. 

PMID- 24449896
TI  - Programmed Allee effect in bacteria causes a tradeoff between population spread
      and survival.
AB  - Dispersal is necessary for spread into new habitats, but it has also been shown
      to inhibit spread. Theoretical studies have suggested that the presence of a
      strong Allee effect may account for these counterintuitive observations.
      Experimental demonstration of this notion is lacking due to the difficulty in
      quantitative analysis of such phenomena in a natural setting. We engineered
      Escherichia coli to exhibit a strong Allee effect and examined how the Allee
      effect would affect the spread of the engineered bacteria. We showed that the
      Allee effect led to a biphasic dependence of bacterial spread on the dispersal
      rate: spread is promoted for intermediate dispersal rates but inhibited at low or
      high dispersal rates. The shape of this dependence is contingent upon the initial
      density of the source population. Moreover, the Allee effect led to a tradeoff
      between effectiveness of population spread and survival: increasing the number of
      target patches during dispersal allows more effective spread, but it
      simultaneously increases the risk of failing to invade or of going extinct. We
      also observed that total population growth is transiently maximized at an
      intermediate number of target patches. Finally, we demonstrate that fluctuations
      in cell growth may contribute to the paradoxical relationship between dispersal
      and spread. Our results provide direct experimental evidence that the Allee
      effect can explain the apparently paradoxical effects of dispersal on spread and
      have implications for guiding the spread of cooperative organisms. 

PMID- 24449897
TI  - Quorum sensing controls hyphal initiation in Candida albicans through Ubr1
      mediated protein degradation.
AB  - Candida albicans is the most common cause of invasive fungal infections in
      humans. Its ability to undergo the morphological transition from yeast to hyphal
      growth forms is critical for its pathogenesis. Hyphal initiation requires the
      activation of the cAMP-PKA pathway, which down-regulates the expression of NRG1,
      the major repressor of hyphal development. Hyphal initiation also requires
      inoculation of a small amount of C. albicans cells from overnight culture to
      fresh medium. This inoculation releases the inhibition from farnesol, a quorum
      sensing molecule of C. albicans, that accumulated in the spent medium. Here, we
      show that farnesol inhibits hyphal initiation mainly through blocking the protein
      degradation of Nrg1. Through screening a kinase mutant library, we identified
      Sok1 as the kinase required for Nrg1 degradation during inoculation. SOK1
      expression is transiently activated on inoculation during hyphal initiation, and
      overexpression of SOK1 overcomes the farnesol-mediated inhibition of hyphal
      initiation. Screening a collection of transcription factor mutants, the
      homeodomain-containing transcription repressor Cup9 is found to be responsible
      for the repression of SOK1 expression in response to farnesol inhibition.
      Interestingly, farnesol inhibits Cup9 degradation mediated by the N-end rule E3
      ubiquitin ligase, Ubr1. Therefore, hyphal initiation requires both the cAMP-PKA
      pathway-dependent transcriptional down-regulation of NRG1 and Sok1-mediated
      degradation of Nrg1 protein. The latter is triggered by the release from farnesol
      inhibition of Cup9 degradation and consequently, derepression of SOK1
      transcription. Neither pathway alone is sufficient for hyphal initiation. 

PMID- 24449898
TI  - Variants of mouse DNA polymerase kappa reveal a mechanism of efficient and
      accurate translesion synthesis past a benzo[a]pyrene dG adduct.
AB  - DNA polymerase kappa (Polkappa) is the only known Y-family DNA polymerase that
      bypasses the 10S (+)-trans-anti-benzo[a]pyrene diol epoxide (BPDE)-N(2)
      deoxyguanine adducts efficiently and accurately. The unique features of Polkappa,
      a large structure gap between the catalytic core and little finger domain and a
      90-residue addition at the N terminus known as the N-clasp, may give rise to its
      special translesion capability. We designed and constructed two mouse Polkappa
      variants, which have reduced gap size on both sides [Polkappa Gap Mutant (PGM) 1]
      or one side flanking the template base (PGM2). These Polkappa variants are nearly
      as efficient as WT in normal DNA synthesis, albeit with reduced accuracy.
      However, PGM1 is strongly blocked by the 10S (+)-trans-anti-BPDE-N(2)-dG lesion.
      Steady-state kinetic measurements reveal a significant reduction in efficiency of
      dCTP incorporation opposite the lesion by PGM1 and a moderate reduction by PGM2.
      Consistently, Polkappa-deficient cells stably complemented with PGM1 GFP-Polkappa
      remained hypersensitive to BPDE treatment, and complementation with WT or PGM2
      GFP-Polkappa restored BPDE resistance. Furthermore, deletion of the first 51
      residues of the N-clasp in mouse Polkappa (mPolkappa(52-516)) leads to reduced
      polymerization activity, and the mutant PGM2(52-516) but not PGM1(52-516) can
      partially compensate the N-terminal deletion and restore the catalytic activity
      on normal DNA. However, neither WT nor PGM2 mPolkappa(52-516) retains BPDE bypass
      activity. We conclude that the structural gap physically accommodates the bulky
      aromatic adduct and the N-clasp is essential for the structural integrity and
      flexibility of Polkappa during translesion synthesis.

PMID- 24449899
TI  - Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster
      yields the antibiotic taromycin A.
AB  - Recent developments in next-generation sequencing technologies have brought
      recognition of microbial genomes as a rich resource for novel natural product
      discovery. However, owing to the scarcity of efficient procedures to connect
      genes to molecules, only a small fraction of secondary metabolomes have been
      investigated to date. Transformation-associated recombination (TAR) cloning takes
      advantage of the natural in vivo homologous recombination of Saccharomyces
      cerevisiae to directly capture large genomic loci. Here we report a TAR-based
      genetic platform that allows us to directly clone, refactor, and heterologously
      express a silent biosynthetic pathway to yield a new antibiotic. With this
      method, which involves regulatory gene remodeling, we successfully expressed a 67
      kb nonribosomal peptide synthetase biosynthetic gene cluster from the marine
      actinomycete Saccharomonospora sp. CNQ-490 and produced the dichlorinated
      lipopeptide antibiotic taromycin A in the model expression host Streptomyces
      coelicolor. The taromycin gene cluster (tar) is highly similar to the clinically
      approved antibiotic daptomycin from Streptomyces roseosporus, but has notable
      structural differences in three amino acid residues and the lipid side chain.
      With the activation of the tar gene cluster and production of taromycin A, this
      study highlights a unique "plug-and-play" approach to efficiently gaining access
      to orphan pathways that may open avenues for novel natural product discoveries
      and drug development. 

PMID- 24449900
TI  - Parameterizing cell-to-cell regulatory heterogeneities via stochastic
      transcriptional profiles.
AB  - Regulated changes in gene expression underlie many biological processes, but
      globally profiling cell-to-cell variations in transcriptional regulation is
      problematic when measuring single cells. Transcriptome-wide identification of
      regulatory heterogeneities can be robustly achieved by randomly collecting small
      numbers of cells followed by statistical analysis. However, this stochastic
      profiling approach blurs out the expression states of the individual cells in
      each pooled sample. Here, we show that the underlying distribution of single-cell
      regulatory states can be deconvolved from stochastic-profiling data through
      maximum-likelihood inference. Guided by the mechanisms of transcriptional
      regulation, we formulated plausible mixture models for cell-to-cell regulatory
      heterogeneity and maximized the resulting likelihood functions to infer model
      parameters. Inferences were validated both computationally and experimentally for
      different mixture models, which included regulatory states for multicellular
      function that were occupied by as few as 1 in 40 cells of the population.
      Importantly, when the method was extended to programs of heterogeneously
      coexpressed transcripts, we found that population-level inferences were much more
      accurate with pooled samples than with one-cell samples when the extent of
      sampling was limited. Our deconvolution method provides a means to quantify the
      heterogeneous regulation of molecular states efficiently and gain a deeper
      understanding of the heterogeneous execution of cell decisions. 

PMID- 24449901
TI  - Spatiotemporal separation of PER and CRY posttranslational regulation in the
      mammalian circadian clock.
AB  - Posttranslational regulation of clock proteins is an essential part of mammalian
      circadian rhythms, conferring sensitivity to metabolic state and offering
      promising targets for pharmacological control. Two such regulators, casein kinase
      1 (CKI) and F-box and leucine-rich repeat protein 3 (FBXL3), modulate the
      stability of closely linked core clock proteins period (PER) and cryptochrome
      (CRY), respectively. Inhibition of either CKI or FBXL3 leads to longer periods,
      and their effects are independent despite targeting proteins with similar roles
      in clock function. A mechanistic understanding of this independence, however, has
      remained elusive. Our analysis of cellular circadian clock gene reporters further
      differentiated between the actions of CKI and FBXL3 by revealing opposite
      amplitude responses from each manipulation. To understand the functional
      relationship between the CKI-PER and FBXL3-CRY pathways, we generated robust
      mechanistic predictions by applying a bootstrap uncertainty analysis to multiple
      mathematical circadian models. Our results indicate that CKI primarily regulates
      the accumulating phase of the PER-CRY repressive complex by controlling the
      nuclear import rate, whereas FBXL3 separately regulates the duration of
      transcriptional repression in the nucleus. Dynamic simulations confirmed that
      this spatiotemporal separation is able to reproduce the independence of the two
      regulators in period regulation, as well as their opposite amplitude effect. As a
      result, this study provides further insight into the molecular clock machinery
      responsible for maintaining robust circadian rhythms. 

PMID- 24449903
TI  - Structure and mechanism of a eukaryotic transmembrane ascorbate-dependent
      oxidoreductase.
AB  - Vitamin C, also known as ascorbate, is required in numerous essential metabolic
      reactions in eukaryotes. The eukaryotic ascorbate-dependent oxidoreductase
      cytochrome b561 (Cyt b561), a family of highly conserved transmembrane enzymes,
      plays an important role in ascorbate recycling and iron absorption. Although Cyt
      b561 was identified four decades ago, its atomic structure and functional
      mechanism remain largely unknown. Here, we report the high-resolution crystal
      structures of cytochrome b561 from Arabidopsis thaliana in both substrate-free
      and substrate-bound states. Cyt b561 forms a homodimer, with each protomer
      consisting of six transmembrane helices and two heme groups. The negatively
      charged substrate ascorbate, or monodehydroascorbate, is enclosed in a positively
      charged pocket on either side of the membrane. Two highly conserved amino acids,
      Lys(81) and His(106), play an essential role in substrate recognition and
      catalysis. Our structural and biochemical analyses allow the proposition of a
      general electron transfer mechanism for members of the Cyt b561 family. 

PMID- 24449904
TI  - Comprehensive structural model of the mechanochemical cycle of a mitotic motor
      highlights molecular adaptations in the kinesin family.
AB  - Kinesins are responsible for a wide variety of microtubule-based, ATP-dependent
      functions. Their motor domain drives these activities, but the molecular
      adaptations that specify these diverse and essential cellular activities are
      poorly understood. It has been assumed that the first identified kinesin--the
      transport motor kinesin-1--is the mechanistic paradigm for the entire
      superfamily, but accumulating evidence suggests otherwise. To address the
      deficits in our understanding of the molecular basis of functional divergence
      within the kinesin superfamily, we studied kinesin-5s, which are essential
      mitotic motors whose inhibition blocks cell division. Using cryo-electron
      microscopy and determination of structure at subnanometer resolution, we have
      visualized conformations of microtubule-bound human kinesin-5 motor domain at
      successive steps in its ATPase cycle. After ATP hydrolysis, nucleotide-dependent
      conformational changes in the active site are allosterically propagated into
      rotations of the motor domain and uncurling of the drug-binding loop L5. In
      addition, the mechanical neck-linker element that is crucial for motor stepping
      undergoes discrete, ordered displacements. We also observed large reorientations
      of the motor N terminus that indicate its importance for kinesin-5 function
      through control of neck-linker conformation. A kinesin-5 mutant lacking this N
      terminus is enzymatically active, and ATP-dependent neck-linker movement and
      motility are defective, although not ablated. All these aspects of kinesin-5
      mechanochemistry are distinct from kinesin-1. Our findings directly demonstrate
      the regulatory role of the kinesin-5 N terminus in collaboration with the motor's
      structured neck-linker and highlight the multiple adaptations within kinesin
      motor domains that tune their mechanochemistries according to distinct functional
      requirements.

PMID- 24449905
TI  - Mutational landscape of yeast mutator strains.
AB  - The acquisition of mutations is relevant to every aspect of genetics, including
      cancer and evolution of species on Darwinian selection. Genome variations arise
      from rare stochastic imperfections of cellular metabolism and deficiencies in
      maintenance genes. Here, we established the genome-wide spectrum of mutations
      that accumulate in a WT and in nine Saccharomyces cerevisiae mutator strains
      deficient for distinct genome maintenance processes: pol32Delta and rad27Delta
      (replication), msh2Delta (mismatch repair), tsa1Delta (oxidative stress),
      mre11Delta (recombination), mec1Delta tel1Delta (DNA damage/S-phase checkpoints),
      pif1Delta (maintenance of mitochondrial genome and telomere length), cac1Delta
      cac3Delta (nucleosome deposition), and clb5Delta (cell cycle progression). This
      study reveals the diversity, complexity, and ultimate unique nature of each
      mutational spectrum, composed of punctual mutations, chromosomal structural
      variations, and/or aneuploidies. The mutations produced in clb5Delta/CCNB1,
      mec1Delta/ATR, tel1Delta/ATM, and rad27Delta/FEN1 strains extensively reshape the
      genome, following a trajectory dependent on previous events. It comprises the
      transmission of unstable genomes that lead to colony mosaicisms. This
      comprehensive analytical approach of mutator defects provides a model to
      understand how genome variations might accumulate during clonal evolution of
      somatic cell populations, including tumor cells. 

PMID- 24449902
TI  - Complementary molecular information changes our perception of food web structure.
AB  - How networks of ecological interactions are structured has a major impact on
      their functioning. However, accurately resolving both the nodes of the webs and
      the links between them is fraught with difficulties. We ask whether the new
      resolution conferred by molecular information changes perceptions of network
      structure. To probe a network of antagonistic interactions in the High Arctic, we
      use two complementary sources of molecular data: parasitoid DNA sequenced from
      the tissues of their hosts and host DNA sequenced from the gut of adult
      parasitoids. The information added by molecular analysis radically changes the
      properties of interaction structure. Overall, three times as many interaction
      types were revealed by combining molecular information from parasitoids and hosts
      with rearing data, versus rearing data alone. At the species level, our results
      alter the perceived host specificity of parasitoids, the parasitoid load of host
      species, and the web-wide role of predators with a cryptic lifestyle. As the
      northernmost network of host-parasitoid interactions quantified, our data point
      exerts high leverage on global comparisons of food web structure. However, how we
      view its structure will depend on what information we use: compared with
      variation among networks quantified at other sites, the properties of our web
      vary as much or much more depending on the techniques used to reconstruct it. We
      thus urge ecologists to combine multiple pieces of evidence in assessing the
      structure of interaction webs, and suggest that current perceptions of
      interaction structure may be strongly affected by the methods used to construct
      them. 

PMID- 24449906
TI  - Human Pol zeta purified with accessory subunits is active in translesion DNA
      synthesis and complements Pol eta in cisplatin bypass.
AB  - DNA polymerase zeta (Pol zeta) is a eukaryotic B-family DNA polymerase that
      specializes in translesion synthesis and is essential for normal embryogenesis.
      At a minimum, Pol zeta consists of a catalytic subunit Rev3 and an accessory
      subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as
      the yeast homolog. To date, no vertebrate Pol zeta has been purified for
      biochemical characterization. Here we report purification of a series of human
      Rev3 deletion constructs expressed in HEK293 cells and identification of a
      minimally catalytically active human Pol zeta variant. With a tagged form of an
      active Pol zeta variant, we isolated two additional accessory subunits of human
      Pol zeta, PolD2 and PolD3. The purified four-subunit Pol zeta4 (Rev3-Rev7-PolD2
      PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand
      d(GpG)-cisplatin cross-link than the two-subunit Pol zeta2 (Rev3-Rev7). We show
      that complete bypass of cisplatin lesions requires Pol eta to insert dCTP
      opposite the 3' guanine and Pol zeta4 to extend the primers. 

PMID- 24449907
TI  - Processing of microRNA primary transcripts requires heme in mammalian cells.
AB  - DiGeorge syndrome critical region gene 8 (DGCR8) is the RNA-binding partner
      protein of the nuclease Drosha. DGCR8 and Drosha recognize and cleave primary
      transcripts of microRNAs (pri-miRNAs) in the maturation of canonical microRNAs
      (miRNAs) in animals. We previously reported that human, frog, and starfish DGCR8
      bind heme when expressed in Escherichia coli and that Fe(III) heme activates
      apoDGCR8 in reconstituted pri-miRNA processing assays. However, the physiological
      relevance of heme in miRNA maturation has not been clear. Here, we present a live
      cell pri-miRNA processing assay that produces robust signals and faithfully
      indicates DGCR8 and Drosha activities. We demonstrate that all known heme-binding
      deficient DGCR8 mutants are defective in pri-miRNA processing in HeLa cells.
      DGCR8 contains a previously uncharacterized heme-binding motif, "IPCL," that is
      also required for its activity. Heme availability and biosynthesis in HeLa cells
      positively affect pri-miRNA processing and production of mature miRNA. These
      results establish an essential function for heme in pri-miRNA processing in
      mammalian cells. Our study suggests that abnormal heme biosynthesis and
      degradation may contribute to diseases via miRNA-mediated gene regulation
      networks. 

PMID- 24449908
TI  - Membrane adhesion dictates Golgi stacking and cisternal morphology.
AB  - Two classes of proteins that bind to each other and to Golgi membranes have been
      implicated in the adhesion of Golgi cisternae to each other to form their
      characteristic stacks: Golgi reassembly and stacking proteins 55 and 65 (GRASP55
      and GRASP65) and Golgin of 45 kDa and Golgi matrix protein of 130 kDa. We report
      here that efficient stacking occurs in the absence of GRASP65/55 when either
      Golgin is overexpressed, as judged by quantitative electron microscopy. The Golgi
      stacks in these GRASP-deficient HeLa cells were normal both in morphology and in
      anterograde cargo transport. This suggests the simple hypothesis that the total
      amount of adhesive energy gluing cisternae dictates Golgi cisternal stacking,
      irrespective of which molecules mediate the adhesive process. In support of this
      hypothesis, we show that adding artificial adhesive energy between cisternae and
      mitochondria by dimerizing rapamycin-binding domain and FK506-binding protein
      domains that are attached to cisternal adhesive proteins allows mitochondria to
      invade the stack and even replace Golgi cisternae within a few hours. These
      results indicate that although Golgi stacking is a highly complicated process
      involving a large number of adhesive and regulatory proteins, the overriding
      principle of a Golgi stack assembly is likely to be quite simple. From this
      simplified perspective, we propose a model, based on cisternal adhesion and
      cisternal maturation as the two core principles, illustrating how the most
      ancient form of Golgi stacking might have occurred using only weak cisternal
      adhesive processes because of the differential between the rate of influx and
      outflux of membrane transport through the Golgi. 

PMID- 24449909
TI  - Essential role of poly(ADP-ribosyl)ation in cocaine action.
AB  - Many of the long-term effects of cocaine on the brain's reward circuitry have
      been shown to be mediated by alterations in gene expression. Several chromatin
      modifications, including histone acetylation and methylation, have been
      implicated in this regulation, but the effect of other histone modifications
      remains poorly understood. Poly(ADP-ribose) polymerase-1 (PARP-1), a ubiquitous
      and abundant nuclear protein, catalyzes the synthesis of a negatively charged
      polymer called poly(ADP-ribose) or PAR on histones and other substrate proteins
      and forms transcriptional regulatory complexes with several other chromatin
      proteins. Here, we identify an essential role for PARP-1 in cocaine-induced
      molecular, neural, and behavioral plasticity. Repeated cocaine administration,
      including self-administration, increased global levels of PARP-1 and its mark PAR
      in mouse nucleus accumbens (NAc), a key brain reward region. Using PARP-1
      inhibitors and viral-mediated gene transfer, we established that PARP-1 induction
      in NAc mediates enhanced behavioral responses to cocaine, including increased
      self-administration of the drug. Using chromatin immunoprecipitation sequencing,
      we demonstrated a global, genome-wide enrichment of PARP-1 in NAc of cocaine
      exposed mice and identified several PARP-1 target genes that could contribute to
      the lasting effects of cocaine. Specifically, we identified sidekick-1--important
      for synaptic connections during development--as a critical PARP-1 target gene
      involved in cocaine's behavioral effects as well as in its ability to induce
      dendritic spines on NAc neurons. These findings establish the involvement of PARP
      1 and PARylation in the long-term actions of cocaine.

PMID- 24449911
TI  - Including distantly related taxa can bias phylogenetic tests.

PMID- 24449910
TI  - Inheritance of Trans Chromosomal Methylation patterns from Arabidopsis F1
      hybrids.
AB  - Hybridization in plants leads to transinteractions between the parental genomes
      and epigenomes that can result in changes to both 24 nt siRNA and cytosine
      methylation ((m)C) levels in the hybrid. In Arabidopsis the principle processes
      altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans
      Chromosomal deMethylation (TCdM) in which the (m)C pattern of a genomic segment
      attains the same (m)C pattern of the corresponding segment on the other parental
      chromosome. We examined two loci that undergo TCM/TCdM in the Arabidopsis
      C24/Landsberg erecta (Ler) F1 hybrids, which show patterns of inheritance
      dependent on the properties of the particular donor and recipient chromosomal
      segments. At At1g64790 the TCM- and TCdM-derived (m)C patterns are maintained in
      the F2 generation but are transmitted in outcrosses or backcrosses only by the
      C24 genomic segment. At a region between and adjacent to At3g43340 and At3g43350,
      the originally unmethylated Ler genomic segment receives the C24 (m)C pattern in
      the F1, which is then maintained in backcross plants independent of the presence
      of the parental C24 segment. In backcrosses to an unmethylated Ler allele, the
      newly methylated F1 Ler segment may act as a TCM source in a process comparable
      to paramutation in maize. TCM-derived (m)C patterns are associated with reduced
      expression of both At3g43340 and At3g43350 in F1 and F2 plants, providing support
      for such events influencing the transcriptome. The inheritance of the F1 (m)C
      patterns and the segregation of other genetic and epigenetic determinants may
      contribute to the reduced hybrid vigor in the F2 and subsequent generations. 

PMID- 24449912
TI  - Role of random electric fields in relaxors.
AB  - PbZr(1-x)Ti(x)O3 (PZT) and Pb(Mg1/3Nb2/3)(1-x)Ti(x)O3 (PMN-xPT) are complex lead
      oxide perovskites that display exceptional piezoelectric properties for
      pseudorhombohedral compositions near a tetragonal phase boundary. In PZT these
      compositions are ferroelectrics, but in PMN-xPT they are relaxors because the
      dielectric permittivity is frequency dependent and exhibits non-Arrhenius
      behavior. We show that the nanoscale structure unique to PMN-xPT and other lead
      oxide perovskite relaxors is absent in PZT and correlates with a greater than
      100% enhancement of the longitudinal piezoelectric coefficient in PMN-xPT
      relative to that in PZT. By comparing dielectric, structural, lattice dynamical,
      and piezoelectric measurements on PZT and PMN-xPT, two nearly identical compounds
      that represent weak and strong random electric field limits, we show that
      quenched (static) random fields establish the relaxor phase and identify the
      order parameter.

PMID- 24449913
TI  - Do close relatives make bad neighbors?

PMID- 24449916
TI  - Retraction for Akimoto et al., Testis-specific protein on Y chromosome (TSPY)
      represses the activity of the androgen receptor in androgen-dependent testicular
      germ-cell tumors.

PMID- 24449914
TI  - Structural basis for nuclear import of splicing factors by human Transportin 3.
AB  - Transportin 3 (Tnpo3, Transportin-SR2) is implicated in nuclear import of
      splicing factors and HIV-1 replication. Herein, we show that the majority of
      cellular Tnpo3 binding partners contain arginine-serine (RS) repeat domains and
      present crystal structures of human Tnpo3 in its free as well as GTPase Ran- and
      alternative splicing factor/splicing factor 2 (ASF/SF2)-bound forms. The flexible
      beta-karyopherin fold of Tnpo3 embraces the RNA recognition motif and RS domains
      of the cargo. A constellation of charged residues on and around the arginine-rich
      helix of Tnpo3 HEAT repeat 15 engage the phosphorylated RS domain and are
      critical for the recognition and nuclear import of ASF/SF2. Mutations in the same
      region of Tnpo3 impair its interaction with the cleavage and polyadenylation
      specificity factor 6 (CPSF6) and its ability to support HIV-1 replication. Steric
      incompatibility of the RS domain and RanGTP engagement by Tnpo3 provides the
      mechanism for cargo release in the nucleus. Our results elucidate the structural
      bases for nuclear import of splicing factors and the Tnpo3-CPSF6 nexus in HIV-1
      biology. 

PMID- 24449915
TI  - Characterization of the IL-15 niche in primary and secondary lymphoid organs in
      vivo.
AB  - IL-15 is a cytokine critical for development, maintenance, and response of T
      cells, natural killer (NK) cells, NK T cells, and dendritic cells. However, the
      identity and distribution of IL-15-expressing cells in lymphoid organs are not
      well understood. To address these questions, we established and analyzed IL-15
      CFP knock-in mice. We found that IL-15 was highly expressed in thymic medulla,
      and medullary thymic epithelial cells with high MHC class II expression were the
      major source of IL-15. In bone marrow, IL-15 was detected primarily in VCAM
      1(+)PDGFRbeta(+)CD31(-)Sca-1(-) stromal cells, which corresponded to previously
      described CXCL12-abundant reticular cells. In lymph nodes, IL-15-expressing cells
      were mainly distributed in the T-cell zone and medulla. IL-15 was expressed in
      some fibroblastic reticular cells and gp38(-)CD31(-) double-negative stromal
      cells in the T-cell zone. Blood endothelial cells, including all high endothelial
      venules, also expressed high IL-15 levels in lymph nodes, whereas lymphatic
      endothelial cells (LECs) lacked IL-15 expression. In spleen, IL-15 was expressed
      in VCAM-1(+) stromal cells, where its expression increased as mice aged. Finally,
      IL-15 expression in blood and LECs of peripheral lymphoid organs significantly
      increased in LPS-induced inflammation. Overall, we have identified and
      characterized several IL-15-expressing cells in primary and secondary lymphoid
      organs, providing a unique perspective of IL-15 niche in immune microenvironment.
      This study also suggests that some stromal cells express IL-7 and IL-15
      differentially and suggests a way to functionally classify different stromal cell
      subsets. 

PMID- 24449918
TI  - Retraction for Yoshimura et al., Distinct function of 2 chromatin remodeling
      complexes that share a common subunit, Williams syndrome transcription factor
      (WSTF).

PMID- 24449917
TI  - PIKE is essential for oligodendroglia development and CNS myelination.
AB  - Oligodendrocyte (OL) differentiation and myelin development are complex events
      regulated by numerous signal transduction factors. Here, we report that
      phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and
      myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor
      cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase
      enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell
      differentiation. In both conventional PIKE knockout (PIKE(-/-)) and OL-specific
      PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE(-/
      ) OLs also display defects when forming myelin sheath on neuronal axons during
      neonatal development, which is partially rescued when PTEN is ablated. In
      addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE(-/-)
      mutant, leading to reduced expression of critical proteins for myelin development
      and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is
      delayed in PIKE(-/-) brain. Thus, PIKE plays pivotal roles to advance OL
      development and myelinogenesis through Akt/mTOR activation. 

PMID- 24449919
TI  - Doxorubicin-induced carbonylation and degradation of cardiac myosin binding
      protein C promote cardiotoxicity.
AB  - Dose-dependent oxidative stress by the anthracycline doxorubicin (Dox) and other
      chemotherapeutic agents causes irreversible cardiac damage, restricting their
      clinical effectiveness. We hypothesized that the resultant protein oxidation
      could be monitored and correlated with physiological functional impairment. We
      focused on protein carbonylation as an indicator of severe oxidative damage
      because it is irreversible and results in proteasomal degradation. We identified
      and investigated a specific high-molecular weight cardiac protein that showed a
      significant increase in carbonylation under Dox-induced cardiotoxic conditions in
      a spontaneously hypertensive rat model. We confirmed carbonylation and
      degradation of this protein under oxidative stress and prevention of such effect
      in the presence of the iron chelator dexrazoxane. Using MS, the Dox-induced
      carbonylated protein was identified as the 140-kDa cardiac myosin binding protein
      C (MyBPC). We confirmed the carbonylation and degradation of MyBPC using HL-1
      cardiomyocytes and a purified recombinant untagged cardiac MyBPC under metal
      catalyzed oxidative stress conditions. The carbonylation and degradation of MyBPC
      were time- and drug concentration-dependent. We demonstrated that carbonylated
      MyBPC undergoes proteasome-mediated degradation under Dox-induced oxidative
      stress. Cosedimentation, immunoprecipitation, and actin binding assays were used
      to study the functional consequences of carbonylated MyBPC. Carbonylation of
      MyBPC showed significant functional impairment associated with its actin binding
      properties. The dissociation constant of carbonylated recombinant MyBPC for actin
      was 7.35 +/- 1.9 MUM compared with 2.7 +/- 0.6 MUM for native MyBPC. Overall, our
      findings indicate that MyBPC carbonylation serves as a critical determinant of
      cardiotoxicity and could serve as a mechanistic indicator for Dox-induced
      cardiotoxicity. 

PMID- 24449920
TI  - Structure, domain organization, and different conformational states of stem cell
      factor-induced intact KIT dimers.
AB  - Using electron microscopy and fitting of crystal structures, we present the 3D
      reconstruction of ligand-induced dimers of intact receptor tyrosine kinase, KIT.
      We observe that KIT protomers form close contacts throughout the entire structure
      of ligand-bound receptor dimers, and that the dimeric receptors adopt multiple,
      defined conformational states. Interestingly, the homotypic interactions in the
      membrane proximal Ig-like domain of the extracellular region differ from those
      observed in the crystal structure of the unconstrained extracellular regions. We
      observe two prevalent conformations in which the tyrosine kinase domains interact
      asymmetrically. The asymmetric arrangement of the cytoplasmic regions may
      represent snapshots of molecular interactions occurring during trans
      autophosphorylation. Moreover, the asymmetric arrangements may facilitate
      specific intermolecular interactions necessary for trans phosphorylation of
      different KIT autophosphorylation sites that are required for stimulation of
      kinase activity and recruitment of signaling proteins by activated KIT. 

PMID- 24449921
TI  - Promoting invasive species control and eradication in the sea: options for
      managing the tunicate invader Didemnum vexillum in Sitka, Alaska.
AB  - Bioinvasions are a significant force of change--and economic and ecological
      threat--in marine ecosystems. The threat now encroaches on Alaska, which has had
      relatively few invasions compared to other global regions, prompting need to
      develop new incursion response tools. We appraised five 'eco-friendly' immersion
      treatment options (dilute acetic acid, dilute bleach, freshwater, brine and
      hypoxia) at either minute- or hour-scale exposures to kill the invasive tunicate
      Didemnum vexillum. Data revealed 100% treatment efficacy after two minutes in
      acetic acid, ten minutes in bleach, four hours in freshwater and over four hours
      in brine solution. We also demonstrated the importance of monitoring D. vexillum
      recovery for at least three weeks, since seemingly destroyed colonies rebounded
      during this timeframe. Combined, these findings provide insights towards a bay
      scale eradication and post-border management plan applicable to the recent D.
      vexillum incursion in Whiting Harbor, Alaska and other shallow, inshore invasion
      sites.

PMID- 24449922
TI  - Microplastic pollution in the surface waters of the Laurentian Great Lakes.
AB  - Neuston samples were collected at 21 stations during an ~700 nautical mile (~1300
      km) expedition in July 2012 in the Laurentian Great Lakes of the United States
      using a 333 MUm mesh manta trawl and analyzed for plastic debris. Although the
      average abundance was approximately 43,000 microplastic particles/km2, station
      20, downstream from two major cities, contained over 466,000 particles/km2,
      greater than all other stations combined. SEM analysis determined nearly 20% of
      particles less than 1 mm, which were initially identified as microplastic by
      visual observation, were aluminum silicate from coal ash. Many microplastic
      particles were multi-colored spheres, which were compared to, and are suspected
      to be, microbeads from consumer products containing microplastic particles of
      similar size, shape, texture and composition. The presence of microplastics and
      coal ash in these surface samples, which were most abundant where lake currents
      converge, are likely from nearby urban effluent and coal burning power plants.

PMID- 24449923
TI  - Plastic debris in Mediterranean seabirds.
AB  - Plastic debris is often ingested by marine predators and can cause health
      disorders and even death. We present the first assessment of plastic ingestion in
      Mediterranean seabirds. We quantified and measured plastics accumulated in the
      stomach of 171 birds from 9 species accidentally caught by longliners in the
      western Mediterranean from 2003 to 2010. Cory's shearwaters (Calonectris
      diomedea) showed the highest occurrence (94%) and large numbers of small plastic
      particles per affected bird (on average N = 15.3 +/- 24.4 plastics and mass =
      23.4 +/- 49.6 mg), followed by Yelkouan shearwaters (Puffinus yelkouan, 70%, N =
      7.0 +/- 7.9, 42.1 +/- 100.0 mg), Balearic shearwaters (Puffinus mauretanicus,
      70%, N = 3.6 +/- 2.9, 5.5 +/- 9.7 mg) and the rest of species (below 33%, N =
      2.7, 113.6 +/- 128.4 mg). Plastic characteristics did not differ between sexes
      and were not related to the physical condition of the birds. Our results point
      out the three endemic and threatened shearwater species as being particularly
      exposed to plastic accumulation.

PMID- 24449924
TI  - Polybrominated diphenyl ether congeners in the young-of-the-year bluefish,
      Pomatomus saltatrix, from several nursery habitats along the US Atlantic
      coastline.
AB  - Spatial trends of polybrominated diphenyl ether (PBDE) congeners were examined by
      using high resolution gas chromatography-low resolution electron impact mass
      spectrometry (GC-EIMS) in 414 samples of young-of-the-year (YOY) bluefish
      (Pomatomus saltatrix) collected from a total of 29 nursery habitats along the US
      Atlantic coastline from Massachusetts to Florida. Of the 26 target PBDE
      congeners, BDE-47 (4 Br), BDE-100 (5 Br), BDE-49 (4 Br), BDE-99 (5 Br), and BDE
      154 (6 Br) were the five most frequently detected congeners in the order of
      decreasing importance. The sum of the concentrations of five major PBDE
      congeners, referred to as SigmaPBDEs, varied between estuaries and also among
      samples from a given estuary. SigmaPBDEs were lowest in YOY bluefish from
      Vineyard Sound, Nantucket Sound, Great Bay, Delaware Bay, Lynnhaven Bay, Cape
      Lookout, and Crescent Beach, with maximum SigmaPBDE concentrations below 10 ng/g
      wet weight. SigmaPBDEs in three bluefish samples from Stamford Harbor were
      detected at relatively high to unusually high concentrations of 69.1, 205, and
      561 ng/g wet weight. SigmaPBDE values for other Stamford Harbor bluefish were
      generally low. Highest PBDE concentrations were detected in the vicinity of
      industrial and urban locations within the New York-New Jersey metropolitan
      complex. Among them, bluefish from Newark Bay were generally the most
      contaminated with an average SigmaPBDE value of 56.6 +/- 30.8 ng/g wet weight.
      SigmaPBDEs in bluefish from Newark Bay were numerically greater than SigmaPBDEs
      in bluefish from all locations, however these differences were not statistically
      significant. Modest to good correlations between SigmaPBDEs and lipids were
      observed for YOY bluefish from Buzzards Bay, Upper New Bedford Harbor, Lower New
      Bedford Harbor, Outer New Bedford Harbor, Providence Harbor, Housatonic River,
      Norwalk Harbor, Little Neck Bay, Newark Bay, Sandy Hook Bay, Great Bay, Delaware
      Bay, Patuxent River and Crescent Beach. Poor correlations between SigmaPBDE and
      lipids were observed for bluefish from other estuaries. SigmaPBDEs were not
      always correlated with fish length or weight. SigmaPBDEs in YOY bluefish along
      the US Atlantic coastline modestly paralleled SigmaPBDEs in mussels and oysters,
      from not exact but geographically loosely similar locations, reported in the NOAA
      Mussel Watch Program. A number of researchers who used the high resolution mass
      spectrometry reported additional PBDE congeners. Although PBDE congeners we
      report do appear to be the prominent congeners in these studies, it is likely
      that the comparisons will be skewed in certain instances.

PMID- 24449925
TI  - Looking at the aquatic contamination through fish eyes--a faithful picture based
      on metals burden.
AB  - This study describes for the first time metal accumulation in the eyes of native
      golden grey mullet (Liza aurata) coupled with water/sediment quality assessment.
      Sampling was performed in the Tagus estuary (Portugal) where a confined area
      (Barreiro) is severely contaminated by metal/loids. Levels of As, Cu, Pb, Hg and
      Cd in sediments from Barreiro were one order of magnitude higher than those from
      the reference site. Data on water column pointed also to a higher availability of
      Cu, Pb, Cd and Hg (including MeHg) at Barreiro. Accordingly, fish eyes
      accumulated higher levels of metal/loids at Barreiro than at the reference site.
      These findings support the use of fish eyes as a target organ in environmental
      health assessment since they reflect sediment and water contamination. It points
      also to the importance of evaluate eye changes at structural/functional levels in
      order to examine in what extent accumulated metals could compromise this
      perceptive system.

PMID- 24449926
TI  - Proceedings of the 5th European Conference on Bloodstream Infections, November 11
      12, 2012, Limassol, Cyprus.

PMID- 24449927
TI  - Proceedings of the 19th International Symposium on Electro- and Liquid Phase
      separation Techniques, September 30-October 3, 2012, Baltimore, Maryland.

PMID- 24449928
TI  - Proceedings of the IV International Giardia and Cryptosporidium Conference, 31
      January-03 February 2012, Wellington, New Zealand.

PMID- 24449929
TI  - Special section on fluorescence molecular imaging honoring Prof. Roger Tsien, a
      pioneer in biomedical optics.

PMID- 24449930
TI  - Special issue dedicated to Meinhart Zenk.

PMID- 24449931
TI  - Special issue dedicated to Dr. Jorge Capdevila.

PMID- 24449933
TI  - The effects of nutritional deficiencies, smoking, and systemic disease on
      orthopaedic outcomes.

PMID- 24449932
TI  - Metal binding properties of Escherichia coli YjiA, a member of the metal
      homeostasis-associated COG0523 family of GTPases.
AB  - GTPases are critical molecular switches involved in a wide range of biological
      functions. Recent phylogenetic and genomic analyses of the large, mostly
      uncharacterized COG0523 subfamily of GTPases revealed a link between some COG0523
      proteins and metal homeostasis pathways. In this report, we detail the
      bioinorganic characterization of YjiA, a representative member of COG0523
      subgroup 9 and the only COG0523 protein to date with high-resolution structural
      information. We find that YjiA is capable of binding several types of transition
      metals with dissociation constants in the low micromolar range and that metal
      binding affects both the oligomeric structure and GTPase activity of the enzyme.
      Using a combination of X-ray crystallography and site-directed mutagenesis, we
      identify, among others, a metal-binding site adjacent to the nucleotide-binding
      site in the GTPase domain that involves a conserved cysteine and several
      glutamate residues. Mutations of the coordinating residues decrease the impact of
      metal, suggesting that metal binding to this site is responsible for modulating
      the GTPase activity of the protein. These findings point toward a regulatory
      function for these COG0523 GTPases that is responsive to their metal-bound state.

PMID- 24449935
TI  - Proceedings of the Tuscany Endocrinology and Metabolism Conference Pisa, 4-6
      April 2013.

PMID- 24449934
TI  - Personalized reproductive medicine on the brink: progress, opportunities and
      challenges ahead.
AB  - Significant progress has been made in several fields of medicine towards
      personalizing treatment recommendations based on individual patient genotype. As
      the number of clinical and genetic biomarkers available to physicians has
      increased, predictive models able to integrate the contributions of multiple
      variables simultaneously have become valuable tools for medical decision making.
      Leveraging genotype information and multivariate predictive models holds the
      promise of bringing greater efficiency to, and reducing the costs of, fertility
      treatments. This work reviews the advances that have been made in genetic
      biomarker discovery and predictive modelling for fertility treatment outcomes. We
      also discuss some of the limitations of these studies for translation to clinical
      diagnostics and the challenges that remain.Personalized medicine holds the
      promise of allowing doctors to create 'bespoke' treatment recommendations for
      each patient based on multiple clinical variables such as age and hormone
      concentrations combined with the patient's genetic sequence information. A number
      of challenges remain for the field of reproductive medicine to make the research
      discoveries necessary to usher in this new era of personalized fertility care.
      Here, we discuss some of these challenges and make recommendations for overcoming
      them.

PMID- 24449936
TI  - Hearing above the din of a katydid's cocktail party.

PMID- 24449937
TI  - Antennae's mechanical role in escaping.

PMID- 24449938
TI  - The life acidic: tubeworms' survival in future oceans.

PMID- 24449939
TI  - Survival of the stressed.

PMID- 24449940
TI  - David Hubel 1926-2013.

PMID- 24449941
TI  - The worldwide landscape of stroke in the 21st century.

PMID- 24449942
TI  - India should introduce a new Drugs Act.

PMID- 24449943
TI  - Searching for Semmelweis.

PMID- 24449946
TI  - Increased air stability and decreased dehydrogenation temperature of LiBH(4) via
      modification within poly(methylmethacrylate.
AB  - An air-stable LiBH4 polymeric composite was successfully prepared by modifying
      LiBH4 with a gas-barrier polymer matrix, poly-(methylmethacrylate) (PMMA). The as
      prepared LiBH4@PMMA composite started to dehydrogenate at 53  degrees C with the
      first main dehydrogenation peak at 116  degrees C, and 5.2 wt% of hydrogen
      released at 162  degrees C within 1 h.

PMID- 24449945
TI  - Effect of ligand substituent on the reactivity of Ni(II) complexes towards
      oxygen.
AB  - Two radical-containing Ni(II) complexes having either parent salicylidene
      (complex 1) or 3,5-di-tert-butylsalicylidene (complex 2) in the ligand backbone
      were synthesized. Complex 2 underwent ligand centered C-H activation by aerial
      oxygen, forming the corresponding amide complex (2a). The UV-Vis/NIR spectral
      changes upon purging of molecular oxygen to 2 in CH2Cl2, alongwith ESI-MS
      analysis indicated the generation of Ni-oxygen/dioxygen species as the
      intermediate(s) for the amide formation. Interestingly, nonparticipation of the
      ligand centered pi-radical in the oxidation process was observed.

PMID- 24449944
TI  - Global and regional burden of stroke during 1990-2010: findings from the Global
      Burden of Disease Study 2010.
AB  - BACKGROUND: Although stroke is the second leading cause of death worldwide, no
      comprehensive and comparable assessment of incidence, prevalence, mortality,
      disability, and epidemiological trends has been estimated for most regions. We
      used data from the Global Burden of Diseases, Injuries, and Risk Factors Study
      2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990
      2010. METHODS: We searched Medline, Embase, LILACS, Scopus, PubMed, Science
      Direct, Global Health Database, the WHO library, and WHO regional databases from
      1990 to 2012 to identify relevant studies published between 1990 and 2010.We
      applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific,
      pre-specified associations between incidence, prevalence, and mortality, to
      calculate regional and country-specific estimates of stroke incidence,
      prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age
      group (<75 years, >= 75 years, and in total)and country income level (high
      income, and low-income and middle-income) for 1990, 2005, and 2010. FINDINGS: We
      included 119 studies (58 from high-income countries and 61 from low-income and
      middle-income countries). From 1990 to 2010, the age-standardised incidence of
      stroke significantly decreased by 12% (95% CI 6-17)in high-income countries, and
      increased by 12% (-3 to 22) in low-income and middle-income countries, albeit
      nonsignificantly. Mortality rates decreased significantly in both high income
      (37%, 31-41) and low-income and middle income countries (20%, 15-30). In 2010,
      the absolute numbers of people with fi rst stroke (16?9 million), stroke
      survivors (33 million), stroke-related deaths (5?9 million), and DALYs lost (102
      million) were high and had significantly increased since 1990 (68%, 84%, 26%, and
      12% increase, respectively), with most of the burden (68?6% incident strokes,
      52?2% prevalent strokes, 70?9% stroke deaths, and 77?7% DALYs lost) in low-income
      and middle-income countries. In 2010, 5?2 million (31%) strokes were in children
      (aged <20 years old) and young and middle-aged adults(20-64 years), to which
      children and young and middle-aged adults from low-income and middle-income
      countries contributed almost 74 000 (89%) and 4?0 million (78%), respectively, of
      the burden. Additionally, we noted significant geographical differences of
      between three and ten times in stroke burden between GBD regions and countries.
      More than 62% of new strokes, 69?8% of prevalent strokes, 45?5% of deaths from
      stroke, and 71?7% of DALYs lost because of stroke were in people younger than 75
      years. INTERPRETATION: Although age-standardised rates of stroke mortality have
      decreased worldwide in the past two decades,the absolute number of people who
      have a stroke every year, stroke survivors, related deaths, and the overall
      global burden of stroke (DALYs lost) are great and increasing. Further study is
      needed to improve understanding of stroke determinants and burden worldwide, and
      to establish causes of disparities and changes in trends in stroke burden between
      countries of different income levels. FUNDING: Bill & Melinda Gates Foundation.

PMID- 24449947
TI  - [Stop the" surgeon shortage" what could be done and what should be done now.
      Series 1: introduction].

PMID- 24449948
TI  - Sodium chloride-dependent oxalate absorption in the human gut.
AB  - We investigated the effect of sodium chloride intake on oxalate and calcium
      metabolism in the human body. In healthy subjects with a simultaneous intake of
      sodium oxalate (4 MUmoles/kg body weight) and sodium chloride (1.2 mmoles/kg body
      weight), the change in oxalate-creatinine ratio was 2.04 +/- 0.74, and 3.25 +/-
      1.29 (means +/- SD), respectively, after 2 and 4 hours of oxalate intake (n = 8).
      The magnitude of the change in the ratio was significantly greater in the case
      with simultaneous intake of sodium chloride and sodium oxalate in comparison to
      the case with an intake of sodium oxalate alone (P < 0.05 and P < 0.01 after 2
      and 4 hours of intake of oxalate, respectively). In subjects with an intake of
      sodium chloride alone, the change in calcium-creatinine ratio was 49.07 +/- 29.96
      and 0.363 +/- 0.309 (means +/- SD), respectively, after 2 and 4 hours of sodium
      chloride intake (n = 3). The results suggest that high sodium intake can be one
      of the risk factors for urolithiasis.

PMID- 24449949
TI  - New oxalate-degrading bacterium from human feces.

PMID- 24449950
TI  - Dissolution of residual microfragments with citrate therapy after extracorporeal
      shock wave lithotripsy.
AB  - Residual microfragments after ESWL were studied for their presence and for
      possibility of dissolution with citrate therapy. Among 123 patients with renal
      stones who became stone-free following ESWL, a computed tomogram (CT) identified
      remaining microfragments within the treated kidney in 31.7% of the patients, even
      though stone fragments were not detectable on ordinary x-ray (KUU). The
      experiments, in which calcium oxalate stone fragments collected after ESWL were
      incubated in buffer solutions with citrate 0 to 4 mmol/L, showed that citrate
      dissolved the stone fragments. Using human urine as a solution, the dissolving
      effect was greater in spot urines after alkali citrate administration than in
      control urines. Eighteen patients with microfragments underwent a follow-up CT 3
      months later. The results showed that the microfragments had disappeared in 6 of
      11 (54.5%) patients who had been taking alkali citrate, whereas microfragments
      remained unchanged in all 5 patients without medication. Our results suggest that
      citrate therapy would be advisable as a prophylaxis for stone recurrence
      especially after ESWL treatment.

PMID- 24449951
TI  - Regulation of the expression of OPN mRNA in the rat as an experimental model of
      renal stone disease.
AB  - We have sequenced a cDNA of calcium oxalate urinary stone protein extracted with
      EDTA. cDNA sequences showed complete homology between urinary stone protein and
      human osteopotine (OPN, bone sialoprotein 1). In this study, we investigated the
      expression of OPN mRNA in rat kidney serving as experimental models for several
      conditions that are considered to be risk factors in human renal stone formation.
      In the renal stone formation model, the expression of OPN mRNA in the distal
      convoluted tubule of the kidney was enhanced compared with the control which was
      found sporadically positive by in situ hybridization. By Northern blot analysis,
      the expression of OPN mRNA was increased in pyelonephritis and hydronephrosis
      models compared with the control, but no changes were observed in dietary-acid or
      base-loading models. The expression of OPN mRNA was markedly inhibited in the
      renal stone formation model by concomitant administration of estradiol and/or
      progesterone.

PMID- 24449952
TI  - Role of rBAT gene products in cystinuria.
AB  - To investigate whether rBAT gene products function as a crystine transporter
      component or as a transport activator, we microinjected several C-terminal
      deletion mutants of rBAT cRNA into Xenopus oocytes, and measured transport
      activity for arginine, leucine and cystine in the presence and absence of sodium.
      Wild type rBAT significantly stimulated the uptake of all 3 amino acids 10-20
      fold compared to control mutants. On the other hand, no mutant, except a Delta511
      685 mutant, stimulated the uptake of these amino acids. However, the Delta511-685
      mutant significantly increased the uptake of arginine. In the presence of sodium,
      the Delta511-685 mutant also increased the uptake of leucine. The Delta511-685
      mutant did not stimulate crystine uptake in the presence and absence of sodium.
      Furthermore, inhibition of L-arginine uptake by L-homoserine was seen only in the
      presence of sodium. These results suggest that mutant rBAT stimulates the
      endogenous amino acid transport system y+ in oocytes. Finally, rBAT gene
      products, as the primary cause of cystinuria, may function as activators of the
      amino acid transport system in renal brush border membrane.

PMID- 24449953
TI  - Preventive effects of eastern medication (Kampo) on the progression of chronic
      renal failure.
AB  - Twenty-two patients with chronic renal failure (CRF) were investigated. The
      patients were mainly administered decoctions of rhubarb (symbol in text) for 4
      weeks. After that, traditional Chinese (Kampo) prescriptions, most of them
      involving Wen-Pi-Tang were given for another 4 weeks. Following administration of
      these prescriptions, the levels of serum methylguanidine (MG), blood urea
      nitrogen and serum inorganic phosphorus improved significantly, although the
      values of serum creatinine (Cr) were not changed remarkably. The fact that the
      serum MG/Cr ratio was reduced after the therapy suggested that rhubarb possessed
      the potential to scavenge hydroxyl radicals by which MG was produced from Cr
      through creatol, as reported recently. The serum Cr concentration was determined
      over an observation period of more than 40 weeks in each of the 7 cases.
      Evaluation of the progression rate of CRF was made from the slopes of the
      regression lines. After analysis, 5 of the 7 cases showed significant retardation
      of progression after the administration of Kampo prescriptions during 106 +/- 32
      (mean +/- SD) weeks. Of the 5 cases, 2 were prescribed Wen-Pi-Tang, another 2
      cases were treated with Wen-Pi-Tang and Bu-Zhong-Yi-Qi-Tang and the last was
      treated with Ba-Wei-Di-Huang-Wan. This study demonstrated that the traditional
      Chinese prescriptions, most of them comprising Wen-Pi-Tang and/or Bu-Zhong-Yi-Qi
      Tang, retarded the progression of CRF.

PMID- 24449954
TI  - Overview of the present and future of clinical transplantation.
AB  - An historical overview of kidney transplantation including the rehabilitation
      status of long-term survivors, the ethical issues related to current American
      transplantation, and projections for the future are presented.

PMID- 24449955
TI  - Twenty years of renal transplantation in children.
AB  - Two hundred and sixty-eight renal transplant operations were done in 244 children
      over the past 20 years. The donors were parents in 229 cases, living relatives in
      another 1 3 eases, and cadavers in the remaining 26 cases. There were 242 first
      grafts, 22 second grafts, and 4 third grafts. The initial 130 grafts were carried
      out with conventional immunosuppressive regimens and the subsequent 1 38 were
      done using immunosuppression including cyclosporin-A. In January 1995, 186
      recipients (76.2%) were alive with functioning grafts, 33 (1 3.5%) were alive on
      dialyses, and 25 (10.2%) were dead. The management results in terms of patient
      and graft survival, as well as the causes of graft failure and patient death are
      described.

PMID- 24449956
TI  - Donor-specific blood transfusion inhibits the allograft response: possible
      regulation by nitric oxide and prostaglandin E2.
AB  - We investigated the effective mechanisms of donor-specific blood transfusion
      (DST) using a sponge matrix allograft animal model. Sponges were harvested on
      various days postgrafting, and both the sponge infiltrating cells and sponge
      exudate fluid (SEF) were collected. DST completely suppressed cytotoxic T
      lymphocyte activity throughout the postgrafting period. SEF *N = O concentration
      (measured as nitrite) in DST mice was significantly lower than in ST mice.
      Conversely, the amount of PGE2 in the SEF from DST mice was higher than in ST
      mice. L)ST may induce intragraft suppressor factors (such as PCE2), resulting in
      reduced immune activation with suppression of local immune response.

PMID- 24449957
TI  - Microchimerism in female renal transplant recipients from male donors.
AB  - Microchimerism in 23 female renal transplant recipients from male donors was
      studied using nested polymerase chain reaction (nPCR) and fluorescence in situ
      hybridization (FISH) to detect Y-chromosome. nPCR was a sensitive and specific
      assay enabling a detection rate of 1/10(6) male/female cells, compared with a
      sensitivity of 1/10(2) by standard PCR (sPCR). None of the 23 patients with a
      male allograft demonstrated Y-chromosome using sPCR. In contrast, 1 3 (56.5%)
      patients demonstrated Y-chromosome with nPCR. Of 9 patients proven to have
      microchimerism by nPCR, only 3 also demonstrated Y-chromosome using FISH. The
      existence of B cells and CD8 cells in donor chimeric cells were proved by
      separation with Dynabeads class I and class II. Dynamic changes of microchimerism
      occurred in 4 of 5 patients. Four patients were proven to have microchimerism
      within a year of transplantation and the microchimerism later disappeared in 3,
      although the sequential change was variable in individual patients. There was no
      correlation between microchimerism and patients'clinical factors such as donor
      specific blood transfusion, HLA matching, immunosuppression, past history of
      acute rejection and chronic rejection. The degree of microchimerism in renal
      transplant recipients was relatively low, and its existence did not seem to be
      compatible with long-term graft acceptance. However, further studies are required
      to elucidate the immunological mechanism of microchimerism, and it might be an
      important clue to immunological tolerance.

PMID- 24449958
TI  - Early prognoses of 200 renal allografts harvested from non-heart-beating
      cadavers.
AB  - When the concept of brain death is not widely accepted, the viability of renal
      allografts of non-heart-beating cadaveric donors is one of the serious concerns
      for transplant surgeons. At our center, 200 kidneys were harvested from cardiac
      arrest donors using the regional in situ cooling technique, and they were
      transplanted into recipients treated with cyclosporine (CS). The ages of donors
      ranged from 7 months to 67 years. At the bedside a specially designed double
      balloon catheter, 14F, was inserted into the aorta through the femoral artery
      just before or immediately after the cardiac arrest. A venous drainage tube was
      also placed in the vena cava. Following the cardiac arrest, both balloons of the
      aortic catheter were inflated, and regional in situ cooling with cold Lactate
      Ringer's solution started using the infusion pump at 20 mL/kg/min. In the OR,
      both kidneys were removed en bloc and preserved in Collins'type solution. They
      were then transplanted into 200 patients treated with CS and steroid. After the
      transplant operations, 33 patients (16.5%) had immediate renal function, but 14
      grafts (7.0%) were not successful and the patients have never had renal function.
      When several factors such as donor age, warm ischemic time (WIT; 12.3 +/- 14.1
      minutes), in situ cooling time (IST; 78.1 +/- 18.0 minutes) and total ischemic
      time (TIT; 619 +/- 340 minutes) were associated with the post-transplant renal
      function, only the donor age had significant correlation both with the
      posttransplant dialysis period and lowest serum creatine level, as follows: 10.5
      days ( <= 40 years) vs. 14.6 days ( > 40 years); P < 0.05, and 1.16 mg/dL ( <= 30
      years) vs. 1.83 mg/dL ( > 50 years) P < 0.001, respectively. Our findings
      indicate; 1) Due to the in situ cooling technique, the renal grafts of non-heart
      beating cadavers can be expected to have relatively good function in the CS
      treated recipients; 2) donor age is instrumental in predicting post-transplant
      renal function as well as the duration of ATN; 3) WIT, 1ST and TIT have no
      association with the post-transplant renal function if the duration of renal
      ischemia is within the acceptable range.

PMID- 24449959
TI  - Outpatient parenteral antimicrobial therapy at large Veterans Administration
      medical center.
AB  - OBJECTIVES: To evaluate our outpatient parenteral antimicrobial therapy (OPAT)
      program to determine its impact on infection management in a facility notable for
      high patient comorbidity and a large catchment area that includes most of
      Southern California. STUDY DESIGN: Retrospective chart review. METHODS: We
      reviewed all episodes of patients receiving OPAT from our institution from 2006
      through 2009 for patient utilization characteristics and assessment of
      complications. RESULTS: A total of 333 patients received 393 courses of OPAT for
      a mean of 21.1 days. Diabetes mellitus (53.5%), psychiatric disease (39%), and
      chronic kidney disease (31%) were common; more than half the patients lived more
      than 20 miles from our medical center. Osteomyelitis (39.7%) and bacteremia
      (19.3%) accounted for the majority of OPAT indications. Staphylococcus aureus
      (36.4%) was the most frequent infecting organism, and vancomycin (37.4%) was the
      most frequently prescribed medication. Complications including hospital
      readmission, adverse drug reactions, or line-related complications were noted in
      96 of 393 (24.4%) episodes, but most were minor, reversible, or not directly
      related to the OPAT given. Serious line-related complications that required
      hospital readmission were noted in only 6 (1.5%) episodes. OPAT was completed as
      planned in 313 (79.6%) episodes; end-stage renal disease was associated with OPAT
      noncompletion in multivariable analysis (odds ratio = 2.20, P = .047). We
      estimated that OPAT saved our medical center $4 million per year. CONCLUSIONS:
      Despite our patients' high level of comorbidity and our facility's large
      catchment area, we were able to deliver OPAT successfully and safely with
      significant cost savings.

PMID- 24449960
TI  - Improving pneumococcal and herpes zoster vaccination uptake: expanding pharmacist
      privileges.
AB  - OBJECTIVE: To investigate how state-authorized pharmacist immunization privileges
      influence pharmacist intervention effectiveness in delivering pneumococcal and
      herpes zoster vaccinations and assess the implications these privileges have on
      vaccination rates. STUDY DESIGN: Cross-sectional study of Walgreens vaccination
      records from August 2011 to March 2012. METHODS: A random sample of patients
      having a claim for influenza vaccination in the study period was selected.
      Vaccination uptake rates for pneumococcal disease and herpes zoster were
      calculated for previously unvaccinated patients at high risk for these
      conditions. Rates were examined by state-level pharmacist privileges. RESULTS:
      For states authorizing immunization by protocol or prescriptive authority, the 1
      year pneumococcal vaccination uptake rate for previously unvaccinated, high-risk
      persons was 6.6%, compared with 2.5% for states requiring a prescription (P
      <.0001), and 2.8% for states with no authorization (P <.0001). For herpes zoster,
      the 1-year vaccination uptake rate was 3.3% for states authorizing per
      protocol/prescriptive authority, compared with 2.8% (not significant, P <.05) for
      states authorizing by prescription, and 1.0% for states with no authorization (P
      <.0001). A 148% increase of pneumococcal vaccination and a 77% increase of herpes
      zoster vaccination would result if all states granted pharmacists full
      immunization privileges. CONCLUSIONS: This analysis demonstrates that states that
      offer pharmacists full immunization privileges have higher vaccination uptake
      rates than states with restricted or no authorization. Considering the suboptimal
      vaccination rates of pneumonia and shingles and the public health goals of 2020,
      states with limited or no immunization authorization for pharmacists should
      consider expanding pharmacist privileges for these vaccinations.

PMID- 24449961
TI  - Testimonials do not convert patients from brand to generic medication.
AB  - OBJECTIVES: To assess whether the addition of a peer testimonial to an
      informational mailing increases conversion rates from brand name prescription
      medications to lower-cost therapeutic equivalents, and whether the testimonial's
      efficacy increases when information is added about an affiliation the quoted
      individual shares with the recipient. RESEARCH DESIGN AND METHODS: A total of
      5498 union members were randomly assigned to receive 1 of 3 different
      informational letters: 1 without a testimonial (No Testimonial Group), 1 with a
      testimonial from a person whose shared union affiliation with the recipient was
      not disclosed (Unaffiliated Testimonial Group), and 1 with a testimonial from a
      person whose shared union affiliation with the recipient was disclosed
      (Affiliated Testimonial Group). RESULTS: The conversion rate for the No
      Testimonial Group was 12.2%, which is higher than the Unaffiliated Testimonial
      Group rate of 11.3% and the Affiliated Testimonial Group rate of 11.7%. The
      differences between the groups are not statistically significant. CONCLUSIONS:
      Short peer testimonials do not increase the impact of a mailed communication on
      conversion rates to lower-cost, therapeutically equivalent medications, even when
      the testimonial is presented as coming from a more socially proximate peer

PMID- 24449962
TI  - Adherence, persistence, and switching patterns of dabigatran etexilate.
AB  - OBJECTIVE: To investigate adherence, persistence, and switching in patients
      initiating dabigatran. STUDY DESIGN: Descriptive analysis using pharmacy claims
      databases. METHODS: Patients with a claim for dabigatran and who were
      continuously enrolled in pharmacy benefits for 180 days prior to and 180 days
      following the initiation of dabigatran were identified and stratified by whether
      there was a history of warfarin treatment prior to dabigatran initiation.
      Medication adherence was calculated as the proportion of days covered (PDC).
      Persistence to treatment at 180 days was measured. Among patients who
      discontinued dabigatran, time to initiating warfarin was determined. RESULTS: In
      the overall population, 39.9% of 17,691 patients were nonpersistent to
      dabigatran. The PDC for the warfarin-naive cohort was 0.674 (standard deviation
      [SD] 0.364), and 0.712 (SD 0.354) for the warfarin-experienced cohort. For
      patients persistent to dabigatran, the PDCs for warfarin-naive and warfarin
      experienced cohorts were 0.935 (SD 0.075) and 0.937 (SD 0.074), respectively. In
      patients discontinuing dabigatran, 16.1% of warfarin-naive and 41.1% of
      warfarinexperienced patients initiated warfarin. Among patients discontinuing
      dabigatran, the mean time to discontinuation in warfarin-naive and
      warfarinexperienced cohorts, respectively, was 59.8 (SD 36.2) and 59.6 (SD 36.2)
      days. The mean time to initiating warfarin in warfarin-naive and warfarin
      experienced cohorts, respectively, was 62.5 (SD 47.2) and 60.5 (SD 43.0) days.
      CONCLUSIONS: Two in 5 patients discontinued dabigatran therapy within 6 months,
      and the majority of these patients were not anticoagulated with warfarin upon
      discontinuation. These findings highlight potential gaps in the care of patients
      treated with dabigatran in routine practice.

PMID- 24449963
TI  - [Imaging evaluation for paranasal sinuses and temporal bone region].

PMID- 24449964
TI  - [Progress in the diagnosis and treatment of nasopharyngeal cancer--progress in
      the 50 years since the discovery of EB virus].

PMID- 24449965
TI  - [Management of refractory vertigo].

PMID- 24449966
TI  - [Tannate gelatin (Tasectan) in the treatment of acute diarrhea].

PMID- 24449967
TI  - [Development of a protocol for counseling patients starting with oral
      hypoglycemic agents].
AB  - INTRODUCTION: Counseling of patients filling a first prescription is an essentiaL
      aspect of pharmaceutical care. The use of a protocol summarizing all relevant
      counseling aspects can be a useful tool to standardize pharmaceutical care and to
      promote impLementation. AIM: (1) To develop a protocol for counseling of patients
      starting with oral hypoglycaemic agents (OHA), and (2) to investigate current
      provision of counseling for these patients in Belgian community pharmacies.
      METHOD: Based on literature, a consensus meeting with community pharmacists and
      consultation with physicians, we developed a protocol for counseling patients
      starting OHA. Additionally, an observational study of current provision of
      counseling for patients starting OHA was performed in 90 community pharmacies.
      RESULTS: All pharmacists reported to provide the most important item of our
      protocol, i.e. dose and timing of OHA intake. All other protocol items were
      provided by a smaller proportion of pharmacists: indication (by 64.4% of
      pharmacists), mechanism of action (30.0%), what to do if a dose is missed (3.3%),
      side effects (34.4%), hypoglycaemia (24.4%) and Lifestyle advice (68.9%). About
      45% of pharmacists reported to give written drug information to patients starting
      OHA. Reduction of the administrative workload was most frequently mentioned as
      measure to spend more time on patient counseling. The majority of pharmacists
      considered our protocol as feasible and appLicabLe in daily pharmacy practice.
      CONCLUSION: This study found that current counseLing practices for patients
      starting OHA can be improved. Our protocol could be a useful and feasible tool to
      facilitate implementation of first prescription counseling.

PMID- 24449968
TI  - [Topical diltiazem preparations for the treatment of anal fissures].

PMID- 24449969
TI  - [Adherence to chronic medication: also a frequent problem in Belgium!].
AB  - Medication adherence in chronic conditions such as asthma, type 2 diabetes, heart
      failure, HIV and cancer appears to be a frequent problem. However, the literature
      on adherence in patients who use inhaled corticosteroids (ICS), oral hypoglycemic
      agents, drugs for heart failure, antiretrovirals or oral chemotherapy, contains
      little or no relevant data for Belgium. In the context of a Master thesis in
      Pharmaceutical care at KU Leuven, a quantitative study was performed to determine
      the prevalence of adherence to chronic medication in Belgium. This retrospective,
      cross-sectional study used a database containing refill data of a regional
      pharmacists' association (KLAV). Out of the 603 pharmacies affiliated with this
      association, all 50 pharmacies where HIV medication was delivered, were selected.
      Dispensing data from the selected pharmacies were collected from 01/07/2008 to
      31/12/2009 for five pathologies, i.e.; asthma, type 2 diabetes, heart failure,
      HIV and cancer. Adherence (TT) was calculated with the Medication Refill
      Adherence (MRA) method. In order to determine whether there were associations
      between age, gender, drug class and adherence, Chi-square tests were used.
      Compared with the other patients, cancer patients were the most adherent in
      taking their drugs (median adherence rate = 88%). In addition, this was the only
      group in which the median adherence rate was above the set limit of 80%. The
      patients who were prescribed inhaled corticosteroids were the least adherent
      (median adherence rate = 38%). More than 50% of patients with asthma/COPD, heart
      failure and diabetes were classified as "under-users". Furthermore, the results
      showed a significant association within asthma patients between gender and
      adherence. In asthma, type 2 diabetes, heart failure and HIV patients there was a
      significant relationship between age and adherence and drug class and adherence.
      As the current study has some limitations, the results should be handled with
      caution. Nevertheless, the current study shows that also in Belgium there is a
      problem with medication adherence in chronic conditions, especially in asthma
      patients.

PMID- 24449970
TI  - [Clinical pharmacist intercepts iatrogenic event through medication
      reconciliation: a case report].

PMID- 24449971
TI  - [Fluticasone / formoterol (Flutiform), oral, inhalation].

PMID- 24449972
TI  - [Tegafur/gimeracil/oteracil (Teysuno), by oral administration].

PMID- 24449973
TI  - [Glycopyrronium, by inhalation and oral administration (Seebri)].

PMID- 24449974
TI  - Lung microbiota: genuine or artifact?

PMID- 24449975
TI  - Endovascular treatment of lower extremity ischemia in chronic renal failure
      patients on dialysis: early and intermediate term results.
AB  - BACKGROUND: Peripheral arterial occlusive disease is common in patients with
      chronic renal failure requiring dialysis. Despite the increasing use of
      endovascular revascularization for lower extremity ischemia, the success rates of
      treating lower extremity ischemia in this challenging population remain obscure.
      OBJECTIVES: To assess the results of endovascular revascularization for lower
      extremity ischemia in dialysis patients. METHODS: We conducted a retrospective
      review of all dialysis patients who underwent endovascular treatment for critical
      limb ischemia (CLI) in our institution between 2007 and 2011. Data collected
      included comorbidities, clinical presentation, anatomic distribution of vascular
      lesions, amputation and survival rates. RESULTS: We identified 50 limbs (41
      patients). Indications included gangrene in 22%, non-healing wounds in 45%, rest
      pain in 31%, and debilitating claudication in 4%. Mean follow-up was 12 months (1
      51 months). Nineteen patients required amputations. Freedom from amputation at 5
      years was 40%. Factors associated with amputation included non-healing wounds or
      gangrene (68% and 36% respectively) and diabetes (P < 0.05). The survival rate
      was 80% after 5 years. CONCLUSIONS: Despite improvement in endovascular
      techniques for lower extremity revascularization, the incidence of limb salvage
      among dialysis patients remains poor, resulting in a high rate of major
      amputations.

PMID- 24449976
TI  - The impact of sleep deprivation on sleepiness, risk factors and professional
      performance in medical residents.
AB  - BACKGROUND: Prolonged working hours and sleep deprivation can exert negative
      effects on professional performance and health. OBJECTIVES: To assess the
      relationship between sleep deprivation, key metabolic markers, and professional
      performance in medical residents. METHODS: We compared 35 residents working the
      in-house night shift with 35 senior year medical students in a cross-sectional
      cohort study. The Epworth Sleepiness Scale (ESS) questionnaire was administered
      and blood tests for complete blood count (CBC), blood chemistry panel, lipid
      profile and C-reactive protein (CRP) were obtained from all participants.
      RESULTS: Medical students and medical residents were comparable demographically
      except for age, weekly working hours, reported weight gain, and physical
      activity. The ESS questionnaires indicated a significantly higher and abnormal
      mean score and higher risk of falling asleep during five of eight daily
      activities among medical residents as compared with medical students. Medical
      residents had lower high density lipoprotein levels, a trend towards higher
      triglyceride levels and higher monocyte count than did medical students. CRP
      levels and other laboratory tests were normal and similar in both groups. Among
      the residents, 5 (15%) were involved in a car accident during residency, and 63%
      and 49% reported low professional performance and judgment levels after the night
      shift, respectively. CONCLUSIONS: Medical residency service was associated with
      increased sleepiness, deleterious lifestyle changes, poorer lipid profile, mild
      CBC changes, and reduced professional performance and judgment after working the
      night shift. However, no significant changes were observed in CRP or in blood
      chemistry panel. Larger prospective cohort studies are warranted to evaluate the
      dynamics in sleepiness and metabolic factors overtime.

PMID- 24449977
TI  - Fetal reduction in triplet gestations: twins still fare better.
AB  - BACKGROUND: Reduction of fetal number has been offered in high order multiple
      gestations but is still controversial in triplets. Since recent advances in
      neonatal and obstetric care have greatly improved outcome, the benefits of
      multifetal pregnancy reduction (MFPR) may no longer exist in triplet gestations.
      OBJECTIVES: To evaluate if fetal reduction of triplets to twins improves outcome.
      METHODS: We analyzed the outcome of 80 triplet gestations cared for at Rambam
      Health Care Campus in the last decade; 34 families decided to continue the
      pregnancy as triplets and 46 opted for MFPR to twins. RESULTS: The mean
      gestational age at delivery was 32.3 weeks for triplets and 35.6 weeks for twins
      after MFPR. Severe prematurity (delivery before 32 gestational weeks) occurred in
      37.5% and 7% of twins. Consequently, the rate of severe neonatal morbidity
      (respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular
      hemorrhage) and of neonatal death was significantly higher in unreduced triplets,
      as was the length of hospitalization in the neonatal intensive care unit (31.4
      vs. 15.7, respectively). Overall, the likelihood of a family with triplets to
      take home all three neonates was 80%; the likelihood to take home three healthy
      babies was 71.5%. CONCLUSIONS: MFPR reduces the risk of severe prematurity and
      the neonatal morbidity of triplets. A secondary benefit is the reduction of cost
      of care per survivor. Our results indicate that MFPR should be offered in triplet
      gestations.

PMID- 24449978
TI  - Oculopharyngeal muscular dystrophy among Bulgarian Jews: a new cluster?
AB  - BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) produced by the (GCG)13
      expansion mutation in the PABPN1 gene is frequent among Uzbek Jews in Israel.
      OBJECTIVES: To describe the phenotypic and genotypic features in five Bulgarian
      Jewish patients, from different families, with autosomal dominant OPMD. METHODS:
      We performed clinical follow-up, electrodiagnostic tests and mutation detection.
      Blood samples were obtained after informed consent and DNA was extracted;
      measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD
      mutations were performed according to standard techniques. RESULTS: We identified
      five patients (four females), aged 58 to 71 years, with bilateral ptosis,
      dysphagia, dysphonia (n = 3) and myopathic motor units by electromyography. In
      all patients we noticed proximal weakness of the upper limbs with winging
      scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.
      CONCLUSIONS: OPMD among Bulgarian Jews is produced by a (GCG)13 expansion,
      identical to the mutation in Uzbek Jews and French Canadians. In addition to the
      classical neurological and neuro-ophthalmological features, early shoulder girdle
      weakness is common in Bulgarian Jewish patients; this is an unusual feature
      during the early stages of OPMD produced by the same mutation in other
      populations. We suggest that besides the disease-producing GCG expansion,
      additional ethnicity-related genetic factors may influence the OPMD phenotype.
      OPMD is a rare disease, and the identification of five affected families in the
      rather small Bulgarian Jewish community in Israel probably represents a new
      cluster; future haplotype studies may elucidate whether a founder effect
      occurred.

PMID- 24449979
TI  - Arterial elasticity in obese subjects with coronary slow flow phenomenon.
AB  - BACKGROUND: Coronary slow flow phenomenon (CSFP) is a functional and structural
      disease that is diagnosed by coronary angiogram. OBJECTIVES: To evaluate the
      possible association between CSFP and small artery elasticity in an effort to
      understand the pathogenesis of CSFP. METHODS: The study population comprised 12
      patients with normal coronary arteries and CSFP and 12 with normal coronary
      arteries without CSFP. We measured conjugated diene formation at 234 nm during
      low density lipoprotein (LDL) oxidation, as well as platelet aggregation. We
      estimated, noninvasively, arterial elasticity parameters. Mann-Whitney
      nonparametric test was used to compare differences between the groups. Data are
      presented as mean +/- standard deviation. RESULTS: Waist circumference was 99.2
      +/- 8.8 cm and 114.9 +/- 10.5 cm in the normal flow and CSFP groups, respectively
      (P = 0.003). Four patients in the CSFP group and one in the normal flow group had
      type 2 diabetes. Area under the curve in the oral glucose tolerance test was 22%
      higher in the CSFP than in the normal group (P = 0.04). There was no difference
      in systolic and diastolic blood pressure, plasma concentrations of total
      cholesterol, triglycerides, high density lipoprotein, LDL and platelet
      aggregation parameters between the groups. Lag time required until initiation of
      LDL oxidation in the presence of CuSO4 was 17% longer (P = 0.02) and homocysteine
      fasting plasma concentration was 81% lower (P = 0.05) in the normal flow group.
      Large artery elasticity was the same in both groups. Small artery elasticity was
      5 +/- 1.5 ml/mmHg x 100 in normal flow subjects and 6.1 +/- 1.9 ml/mmHg x 100 in
      the CSFP patients (P = 0.02). CONCLUSIONS: Patients with CSFP had more metabolic
      derangements. Arterial stiffness was not increased in CSFP.

PMID- 24449980
TI  - Outcome of patients with rheumatoid arthritis: cross-sectional study of a single
      center real-world inception cohort.
AB  - BACKGROUND: Tight control of disease activity is the recommended target of
      therapy for rheumatoid arthritis (RA). OBJECTIVES: To determine the outcome of RA
      with respect to disease activity and the rate of remission, as measured by the
      DAS-28, in a real-world inception cohort. METHODS: We conducted an observational
      cross-sectional study of a single-center real-world inception cohort of 101
      consecutive patients being treated for RA in 2009-2010 in a rheumatology
      outpatient clinic. Patients were managed at the discretion of the attending
      rheumatologist with the goal of achieving remission. DAS-28 scores were
      calculated and analyzed by clinical and treatment variables derived from the
      medical files. RESULTS: Mean patient age was 58.6 +/- 13.4 years and mean
      duration of disease 10.7 +/- 7.9years. Disease remission (DAS-28 < 2.6) was
      achieved in 26.7% of patients and low disease activity (> 2 .6 DAS-28 < 3.2) in
      17%. Monotherapy with a conventional disease-modifying anti-rheumatic drug (C
      DMARD, 21% of patients at last follow-up) was associated with a significantly
      lower mean DAS-28 score and C-reactive protein level than combined C-DMARD
      treatment (79% of patients), and with shorter disease duration than combined
      treatment with C-DMARDs or C-DMARD(s)+biological DMARD (40% of patients).
      Rheumatoid factor and anti-cyclic citrullinated peptide positivity had no effect
      on DAS-28 scores. Time from diagnosis was inversely correlated with DAS-28
      scores. CONCLUSIONS: The achievement of low disease activity and remission in a
      significant portion of our inception cohort of patients with RA suggests that the
      treat-to-target strategy is feasible and effective in routine clinical practice.

PMID- 24449981
TI  - Sport-related eye injury in northern Israel.
AB  - BACKGROUND: Eye injuries are common in sports. Sports-related eye injuries have
      the potential for major morbidity OBJECTIVES: To investigate the occurrence and
      to classify sport-related eye trauma in northern Israel. METHODS: We analyzed the
      records of the ophthalmology emergency department for the years 2007-2011 and
      classified the admissions according to type, severity of injury and demographic
      data. RESULTS: In 2% of the patients the injuries occurred during a sport
      activity. Most of the injuries occurred during soccer, basketball or school sport
      activity (74%). The majority of patients were young males. CONCLUSIONS: Most
      sports-related eye injuries can be prevented with adequate eye protection.

PMID- 24449982
TI  - The microbiome of the lung.

PMID- 24449983
TI  - Sleep deprivation among medical residents: different perspectives.

PMID- 24449984
TI  - Is long-term beta-blocker therapy for myocardial infarction survivors still
      relevant in the era of primary percutaneous coronary intervention?
AB  - Studies on trials conducted before the use of thrombolysis demonstrated both
      short- and long-term benefits of beta-blockers, and one meta-analysis of those
      trials showed a 25% reduction in 1 year mortality. Treatment with beta-blockers
      was and continues to be recommended for patients after ST elevation myocardial
      infarction (STEMI), but many patients failed to receive these agents mostly
      because physicians were unconvinced of their benefit. A similar analysis of the
      studies in STEMI patients treated with thrombolysis also showed an overall 23%
      reduction in mortality associated with beta-blocker use in the era of primary
      percutaneous coronary intervention (PCI). In the present review, we examine the
      relationship between the pharmacology of beta-blockers and their potential
      utility in order to review early trials on their post-infarct efficacy and to
      place these findings in the context of this specific patient population in the
      era of primary PCI.

PMID- 24449985
TI  - Immune thrombocytopenic purpura and myocardial infarction: a dilemma of
      management.

PMID- 24449986
TI  - Coagulopathy unmasking hepatic failure in a child with ornithine transcarbamylase
      deficiency.

PMID- 24449987
TI  - Indemonstrable axial spondyloarthritis: does it exist?

PMID- 24449988
TI  - Tuberculosis: a rare cause of peri-anal disease.

PMID- 24449989
TI  - Ovarian carcinoma metastasis to breast: role of PET/CT.

PMID- 24449990
TI  - 11th Medinterna International Meeting: what did we learn?

PMID- 24449991
TI  - The first Israeli fibromyalgia congress, February 2013.

PMID- 24449992
TI  - In high-tech world: stroke rehab remains personal.

PMID- 24449993
TI  - Caring for elders at the top of the world: the northernmost nursing home in the
      country cares for a unique population.

PMID- 24449994
TI  - Parkinson's disease: strong marriages suffer more.

PMID- 24449995
TI  - Service and savings go hand in hand: a nursing home provider shifts to direct
      dining model with great success.

PMID- 24449996
TI  - Group proposes public reporting for assisted living.

PMID- 24449997
TI  - [Apropos of classifications in mental health].

PMID- 24449998
TI  - [Like a ship in a tempest].

PMID- 24449999
TI  - [Changes in adolescence and changes in care].
AB  - Adolescence is a period renowned for giving rise to changes, the outcome of which
      is unknown or uncertain. It is necessary to take into account the malaise,
      resulting from a problem of intersubjectivity and social bonds. Excesses of
      individualism as a response to the weakness of the being are conveyed by risk
      taking behaviour. Caregivers must stay on course, not be discouraged and favour
      creative approaches, either individually or in a team.

PMID- 24450000
TI  - [Difficult teenagers: the challenges of interdisciplinarity].
AB  - The adolescents in great distress, because of ruptures in the course of their
      lives and of their chaotic family environment, need educational and social
      actions. The consensual point of view is that responding to the needs of the so
      called "difficult adolescents" implies the involvement of educational,
      therapeutic and judicial services. Nevertheless, the usual tendency to categorize
      the users with the idea it will permit to guide them to the appropriate skill
      field and the transgressive characteristic of these adolescents' behaviours lead
      all these services to reject them and send them to the two other services.

PMID- 24450001
TI  - [Partnership around difficult teenagers in Brest].
AB  - The issues surrounding difficult teenagers results in professionals formalising a
      partnership. Certain areas of focus are identified such as getting to know each
      other better in order to understand each other better, working in a "common
      language", understanding professional identities, or embracing long term
      partnership. Pressure to assess and rationalise spending, as well as political
      challenges, must be taken into consideration.

PMID- 24450002
TI  - [From eternal love to Transferential love].
AB  - A teenager subject to a relationship break-up offloads his suffering onto a
      clinical psychologist at a medical-psychological centre. The therapy takes place
      over two stages, to construct shoring and thereby steer away from deadly
      thoughts.

PMID- 24450003
TI  - [Bibliography].

PMID- 24450004
TI  - [From the psychiatric sector to the mental health territory].
AB  - There is currently a noticeable change in public health policy, as well as a
      paradigm shift with the policy of a mental health territory. From a humanist
      sector policy, centred on the patient, we are moving towards a policy of a mental
      health territory, which, although taking into account the changing needs of a
      group of people, no longer considers the specific needs of the individual. The
      notion of a geographic breakdown of the organisation of care is becoming
      predominant.

PMID- 24450005
TI  - [An original therapeutic approach: the regulars' table].
AB  - Reintegrating psychotic patients or those suffering from severe personality
      disorders in the relationship with other people is not easy. A part-time therapy
      centre in Saint Louis has developed a specific programme for these patients: the
      Stammtisch, Alsatian for "the regulars' table". Due to the minimal presence of
      the nurses, the patient's desire is brought to the fore. The patients thereby
      spontaneously work on their impaired social interaction.

PMID- 24450006
TI  - [Henri Ey].

PMID- 24450007
TI  - Conversation starters.
AB  - There's an art to bringing docs into partnership discussions.

PMID- 24450008
TI  - The patient experience.
AB  - Learning what patients care about during a hospital stay can improve
      reimbursement and influence quality.

PMID- 24450009
TI  - Easing the bite on the ED.
AB  - With hospitals' help, dental patients can get treatment at the right time and in
      the right setting.

PMID- 24450010
TI  - Using a scorecard for strategic results.

PMID- 24450011
TI  - Leadership lessons from lean.
AB  - Inspired by nearby manufacturing plants, ThedaCare adopted Lean to standardize
      quality.

PMID- 24450012
TI  - New pitfalls in patient safety.
AB  - The old, paper-based process of managing device recalls and safety notices won't
      cut it anymore.

PMID- 24450013
TI  - 12 signs that say 'stay away'.
AB  - An outside expert will look for these 12 warning signs before joining your board.

PMID- 24450014
TI  - Developing a strategic board.
AB  - Becoming a more strategic board doesn't happen on its own.

PMID- 24450015
TI  - Hope for the future.

PMID- 24450016
TI  - Social justice and intercountry adoptions: the role of the U.S. social work
      community.
AB  - Using social justice as the conceptual foundation, the authors present the
      structural barriers to socially just intercountry adoptions (ICAs) that can
      exploit and oppress vulnerable children and families participating in ICAs. They
      argue that such practices threaten the integrity of social work practice in that
      arena and the survival of ICA as a placement option. Government structures,
      disparity of power between countries and families on both sides, perceptions
      regarding poverty, cultural incompetence, misconceptions about orphans and
      orphanages, lack of knowledge about the impact of institution-based care, and the
      profit motive are driving forces behind the growing shadow of unethical ICAs. The
      U.S. social work community has a large role and responsibility in addressing
      these concerns as the United States receives the most children adopted through
      ICAs of all receiving countries. In addition to the centrality of social justice
      as a core value of the profession, the responsibility to carry out ethical and
      socially just ICA has recently increased as a matter of law, under the
      implementation legislation to the Hague Convention on Intercountry Adoption.
      While acknowledging that these issues are complex, authors provide suggestions
      for corrective policy and practice measures.

PMID- 24450017
TI  - Policy practice in practice: the inputs of social workers in legislative
      committees.
AB  - This article presents findings of an empirical study of the involvement of social
      workers in the policy formulation process. Despite support for policy practice,
      there has been limited empirical study of social workers' involvement in policy
      practice, which leaves us with little systematic knowledge of social workers'
      role in the policy formulation process. This study expands the knowledge of
      social workers' role in this process by identifying their inputs into Israeli
      legislative committees. Based on a content analysis of the minutes of 85
      parliamentary committee meetings held during the 15th and 16th Knesset sessions
      (1999 to 2006), the study reveals five main inputs: placing matters on the
      agenda, providing information, providing explanations, expressing opinions and
      making suggestions, and commenting on the manner of the discussion, and 23
      subinputs. These inputs underscore three main functions that social workers
      perform, or may perform, with respect to policy: challenging policy, facilitating
      policy, and enriching policy.

PMID- 24450018
TI  - Indigenous youth participatory action research: re-visioning social justice for
      social work with indigenous youths.
AB  - The NASW Code of Ethics identifies social justice as one of six foundational
      values of the social work profession. Indigenous communities have long questioned
      the authenticity of this commitment and rightly so, given the historical
      activities of social work and social workers. Still, the commitment persists as
      an inspiration for an imperfect, yet determined, profession. This article
      presents a theoretical discussion of questions pertinent for social justice in
      social work practice in Native American communities: Whose definition of social
      justice should prevail in work with and in Indigenous communities? What can a
      revisioning of social justice mean to the development of Native communities and
      for Native youths in particular? What methods or processes of social work are
      most appropriate for this social justice work? This article presents a case for
      the practice of youth participatory action research as one method to work for
      social justice in Native communities.

PMID- 24450019
TI  - Culturally competent and spiritually sensitive therapy with lesbian and gay
      Christians.
AB  - This article presents results from a retrospective qualitative study of 27
      lesbian and gay (LG) Christians that examined religious and spiritual issues and
      resolutions. Participants were also asked to identify the necessary knowledge and
      skills that practitioners (social workers, therapists, pastoral care providers,
      and so on) working with clients who are coming out need to help such clients
      integrate their sexual orientation and religion or spirituality. By analyzing the
      stories of participants, the authors identified information to enhance
      practitioners' cultural competence and spiritual sensitivity. Themes identified
      as important were having a historical perspective, self-awareness, and a
      nonjudgmental attitude; expanding definitions; and understanding the power of
      words. Participants described both their negative and positive experiences in
      integrating their faith and sexual orientation, and offered pragmatic suggestions
      for LG Christians. Themes identified were reframing scripture and tradition,
      supportive pastoral relationships, affirming Christian communities, peer support,
      and educational resources. This article will increase practitioner understanding
      of how to support the integration of sexual orientation and Christianity for LG
      clients who are coming out. It is also a resource for LG Christians who can
      benefit from reading stories of those who have successfully integrated their
      faith and sexual orientation.

PMID- 24450020
TI  - In response to need: an analysis of social work roles over time.
AB  - In this qualitative research synthesis, interviews with 22 early health-related
      social workers were reexamined to identify themes that emerged when these social
      workers discussed the roles and goals of their work. Those interviews, with
      colleagues of Ida M. Cannon and those leaders in the next generation of social
      workers who had practiced during the first half of the 20th century, were
      conducted in 1976. For this study, the themes that emerged from the original
      interview data as social workers' responses to perceived needs were then compared
      with data consisting of 80 cases, drawn from four more recent casebooks (1982,
      1989, 1996, 2010), that followed a framework of practice in context. The
      comparison demonstrated that themes remain consistent over time and include
      responses to needs created by wars, due to new and underserved populations,
      created by public health crises, created by technological advances, experienced
      by organizations, and resulting from economic and policy issues, as well as needs
      of clients. Analysis also suggests that caution is in order to avoid being co
      opted by organizations and others in power at the cost of the profession's social
      justice mission and ethical imperatives.

PMID- 24450021
TI  - Responding to the global economic crisis: inclusive social work practice.
AB  - The present global economic crisis raises new concerns for social workers. One of
      its most visible results is the further socioeconomic decline and marginalization
      of excluded populations. This article suggests that the current circumstances
      require a much more engaged, egalitarian, and reflexive practice-a practice,
      based on social rights, that matches the magnitude of the crisis and its negative
      impact on traditional social work constituencies. Consequently, the article
      suggests the concept of inclusive social work practice (ISWP), a conceptual
      framework whose main principles respond to four processes of social exclusion
      closely related to the present global crisis: extreme social isolation, growing
      dependency, multiple deprivation, and internalized oppression. The author
      describes the impact of the global crisis on patterns of social exclusion and
      presents the methodological foundations of the ISWP framework.

PMID- 24450022
TI  - Assessment of a service provider self-study method to promote interorganizational
      and community collaboration.
AB  - With an emphasis by both public and private funding sources on community-level
      service integration, many social service organizations have been required to
      shift from traditional "silo" models of service delivery to increased community
      based collaboration and service coordination. There is a paucity of research to
      identify successful methods to achieve these goals. This article describes a self
      study method used to engage service providers in a community development effort
      designed to meet the needs identified by local residents within their community
      and empower a rural, unincorporated community with scarce resources. It also
      reports qualitative outcomes that assessed the utility of a self-study method to
      achieve collaboration and community empowerment. Communication, ownership, input,
      and investment among providers appear to be key components to achieving long-term
      sustainability and success. Implications for the utility of the self-study method
      for achieving community service integration that aligns with basic principles of
      community development are discussed.

PMID- 24450023
TI  - Mental Health Literacy: social work's role in improving public mental health.

PMID- 24450024
TI  - A social worker's report from the United Nations conference on sustainable
      development (Rio + 20).

PMID- 24450025
TI  - Five things social workers should know about the DSM-5.

PMID- 24450026
TI  - Practitioners as managers: using and building on existing knowledge.

PMID- 24450027
TI  - [Basic research during residency in Israel: is change needed?].
AB  - A six-month research period is a mandatory part of the residency training program
      in most basic specialties in Israel and is named: the "basic science period".
      This is the only period in an Israeli physician's medical career which is
      dedicated strictly to research, accentuating the importance of medical research
      to the quality of training and level of medicine in Israel. From another point of
      view, one may argue that in an era of shortage of physicians on the one hand and
      the dizzying rate of growth in medical knowledge on the other hand, every moment
      spent training in residency is precious, therefore, making the decision of
      whether to dedicate six months for research becomes ever more relevant. This
      question is currently raised for discussion once again by the Scientific Council
      of the Israeli Medical Association. The Scientific Council lately issued a call
      for comments sent to all Israeli physicians, asking their opinion on several key
      questions regarding basic science research. Learning the public's opinion will
      serve as a background for discussion. A total of 380 physicians responded to the
      call and specified their standpoint on the subject, among them heads of
      departments, units and clinics, senior physicians and residents. The findings
      pointed to strong support in maintaining the research period as part of residency
      training due to its importance to medical training and medicine, although half
      the respondents supported the use of various alternative formats for research
      together with the existing format. Those alternative format suggestions will be
      thoroughly reviewed. A smaller group of respondents supported allowing residents
      a choice between two tracks--with or without a research period, and only a few
      were in favor of canceling the research requirement altogether. The writers
      maintain that the "basic science period" of research during residency training is
      vital and its contribution to the high level of specialists and high level of
      medicine requires its conservation. Nevertheless, alternative formats which might
      be suitable for some residents should be considered, and auxiliary tools to help
      residents fulfill their potential in research and raise the quality of written
      research papers should be constructed.

PMID- 24450028
TI  - [A winning award for the excelling research papers for 2013 on behalf of the
      Israeli Medical Association].

PMID- 24450029
TI  - [Combination of imaging studies and autopsy in death investigations].
AB  - The progress in quality and availability of imaging studies has made them an
      invaluable part of the clinical diagnostic process, so much so that the forensic
      medical community had to acknowledge their importance and to implement them in
      death investigations. Since 2011 roughly 200 post-mortem radiographic
      examinations were conducted, mostly followed by full autopsies. Four of those
      cases are given as an example of the benefits and limitations of these methods. A
      review of the literature and our experience so far, show that computed tomography
      provides better visualization and 3D reconstruction of traumatic bone injuries,
      as well as good assessment of air in the tissues and vascular system, gunshot
      wound tracts, and anthropological characteristics for identification. Imaging
      methods are relatively limited in definite diagnostic findings in cases of sudden
      death from natural causes, such as pneumonia, pulmonary embolism, acute
      myocardial infarction or meningitis, problems which can be partially solved with
      the aid of angiographic studies. These methods also do not allow for sampling of
      tissues for microscopic examination, nor fluid samples for cultures and
      toxicology. In the current cultural and social reality in Israel, imaging studies
      enable minimization of the autopsy and, in certain cases, its relinquishment
      serves as a compromise between the necessity of death investigation and beliefs
      in the wholeness of the body. In light of the advantages of imaging, no autopsy
      of a trauma-related death can be complete without it.

PMID- 24450030
TI  - [Identification of unknown cadavers--multidisciplinary approach].
AB  - The comparison of fingerprints, dentition, genetic profile, imaging data and
      anthropological characteristics constitute the scientific basis for
      identification of unknown cadavers. The complexity of the identification process
      stems from a variety of factors such as the circumstances surrounding the death,
      the preservation state of the cadaver, availability of identification data and
      their quality, which affect the feasibility of the identification. This article
      reviews the most common identification techniques, the various sources of data
      accessible to the forensic scientist and the strategic decisions through which
      the unidentified body and the missing person are integrated.

PMID- 24450031
TI  - [Decitabine treatment in myelodysplastic syndromes--results of a compassionate
      patient program in Israel].
AB  - INTRODUCTION: Hypermethylation of tumor suppressor genes (TSG) has been
      recognized as an important factor in the pathogenesis of malignancies, including
      myelodysplastic syndromes (MDS). Decitabine (trade name Dacogen; 5-aza-2'
      deoxycytidine) is a cytosine analog which inhibits the enzyme DNA
      methyltransferase (DNMT), inducing hypomethylation and activates TSG, leading to
      tumor cell growth inhibition. In clinical trials with hypomethylating agents in
      advanced MDS, a total response rate of 30-73% has been observed, with a complete
      response (CR) of 9-37%, partial response (PR] of similar rate and a hematologic
      improvement (HI] in 20-48% of the patients. AIM: We report the results of a
      national Israeli compassionate program of decitabine administration to patients
      with advanced MDS. PATIENTS AND METHODS: From July 2007 through August 2008,
      under the joint sponsorship of The Israel Society of Hematology and Blood
      Transfusions and Janssen, Israel, a compassionate program was conducted.
      Decitabine was administered to patients with advanced MDS who were not candidates
      for any other anti-MDS treatment, except for supportive care. The selected
      regimen was a 5-day intravenous administration of 20 mg/m/d, every 28 days. After
      the program had been completed, an approval of the institutional Helsinki
      committees was obtained, and the data were collected in an attempt to evaluate
      the results of this novel treatment. The standard response criteria, i.e. total
      response, CR, PR and HI were applied. Toxicity, survival and leukemic
      transformation rate were also analyzed. RESULTS: Twenty-four patients with
      advanced MDS participated in the program but evaluable information could be
      collected only on 17 patients. The median number of therapeutic cycles was two
      per patient. Twelve patients were transfusion-dependent at program onset, of whom
      7 either benefited from reduced transfusion requirements or became transfusion
      free. The overall response rate was 26%, with 23% PR and 13% HI. Two patients
      (13%) demonstrated leukemic transformation. The median overall survival was 17
      months and the median event-free survival was 13 months. Nine out of 12 patients,
      who could be evaluated, experienced 3-4 degree bone marrow suppression. A single
      patient suffered from vocal cord paralysis, apparently, unrelated to the
      treatment. DISCUSSION AND CONCLUSIONS: The overall response rate was 26% in this
      national compassionate program of decitabine administration to patients with
      advanced MDS. Although somewhat low, this is similar to other reports. Possible
      reasons for the relatively low response rate include a small number of patients,
      the nature of a compassionate program, the limited number of therapeutic cycles,
      and the very advanced degree of the disease in most patients who had been on
      several treatment lines prior to the program. Nevertheless, understanding the
      role of epigenetics in the pathogenesis of neoplasms and MDS, which led to the
      introduction of hypomethylation agents such as decitabine into clinical practice,
      is an encouraging step towards better care of cancer, including MDS.

PMID- 24450032
TI  - [Mastoidectomy with reconstruction of the posterior canal wall and obliteration
      preventing postoperative morbidity].
AB  - INTRODUCTION: A cholesteatoma in the mastoid or in the middle ear presents a
      hazard to the well-being of patients. Commonly used surgical interventions are
      not an ideal solution as they bear with them postoperative morbidity such as the
      need for water precautions, a high rate of cholesteatoma recurrence and the
      inability to undergo hearing rehabilitation. METHODS: Forty-five patients
      underwent an innovative surgical procedure that enables complete removal of the
      cholesteatoma, preservation of ear anatomy and hearing restoration. Our series
      was divided into two groups. The first group comprised those in whom this
      innovative procedure was the first one and the posterior bony canal was preserved
      (primary surgery). The second group comprised those in whom the bony wall had
      been removed previously during surgery (secondary surgery). RESULTS: In the first
      group, which included 29 patients, the middle ear cavity was found to be aerated
      in 69% of the patients, the tympanic membrane was intact in 93% and the rate of
      cholesteatoma recurrence was 10.3%. In the second group, which included 16
      patients, the middle ear cavity was found to be aerated in 56.2% of cases, the
      tympanic membrane was intact in 75% and the rate of cholesteatoma recurrence was
      25%. DISCUSSION: Mastoidectomy reconstruction of the posterior wall and
      obliteration (MAPRO) was found to be an effective approach for completely
      removing a choLesteatoma and preventing cholesteatoma recurrence. It is water
      safe and provides an excellent basis for hearing restoration. The use of the
      original posterior bony canal for middle ear reconstruction was found to be
      beneficial. The authors advise an MRI study 18 months after surgery for
      cholesteatoma detection.

PMID- 24450033
TI  - [Use of fertility drugs and risk of breast cancer].
AB  - The strong desire to bring children into the world is the foundation of human
      existence. Fertility problems arise in approximately 10% of the population. The
      literature presents controversies regarding whether fertility treatment and
      ovarian hyperstimulation can be harmful to the patient. Can high estrogen levels
      that accompany the treatment cause or promote breast cancer? Dr. Riskin-Mashiach
      in her article: "Infertility, fertility treatment and breast cancer risk",
      reviews recent articles on the subject and concludes that most studies do not
      indicate a direct link but larger studies are needed to verify the safety of
      these treatments for patients.

PMID- 24450034
TI  - [Infertility, fertility treatment and breast cancer risk].
AB  - Breast cancer is the most common cancer in women in Israel and throughout the
      world. It is the leading cause of death from cancer in women. The cause of breast
      cancer is unknown; however gynecological history and hormonal factors have a
      major impact on the risk to develop breast cancer. Infertility affects 15-20% of
      couples in developed countries and most of them will need fertility treatment.
      The variety of fertility treatments and their use has been widespread during the
      last 50 years and especially since the introduction of in vitro fertilization.
      During fertility treatment, and depending on the type of treatment, there is
      ovarian hyperstimulation with maturation of several follicles and higher than
      normal estradiol levels. This article reviews the leading studies that evaluated
      the possible link between fertility treatment and the development of breast
      cancer. Most studies showed no association between fertility drugs and breast
      cancer. Whereas other researchers demonstrated a possible link between some
      fertility drugs and increased risk for breast cancer in certain subgroups.
      Therefore, larger studies with longer follow-up periods and better control for
      all possible confounding factors are needed in order to confirm the safety of
      fertility treatments in the long run. The combination of infertility and
      fertility treatment might cause harm, such as an increased risk for breast cancer
      Therefore, one has to consider carefully, together with the woman, the need for
      fertility treatment and give the lowest possible dosage for the shortest duration
      in order to minimize the risk.

PMID- 24450035
TI  - [Ganglion cysts of the hand and wrist].
AB  - Ganglion cysts are considered the most common tumor of the wrist and hand. They
      are most common between the second and fourth decades of life. The most common
      anatomical location is the dorsal wrist. This article includes a general review
      of these cysts including symptoms, pathology and methods of diagnosis, as well as
      a review of these cysts in specific anatomic locations. The article also includes
      an updated review of the literature comparing open surgery vs. arthroscopic
      treatment. The authors believe that arthroscopic surgery of ganglion cysts will
      gain an important role in the treatment of these cysts.

PMID- 24450037
TI  - [The relationship between whiplash injury and temporomandibular joint
      dysfunction].
AB  - This article aims to discuss the possible relationship between rapid extension
      flexion of the neck-whiplash injury and temporomandibular disorders (TMD).
      Clinical experience and studies revealed that whiplash injury may cause TMD. The
      pathophysiology of TMD is described as well as clinical and imaging diagnostic
      criteria. The treatment modalities for TMD are: physiotherapy, nonsteroidal anti
      inflammatory drugs and occlusal splints.

PMID- 24450036
TI  - [Chronic exertional compartment syndrome].
AB  - Chronic exertional compartment syndrome is an uncommon phenomenon first reported
      in the mid 50's. This condition is characterized by sharp pain during physical
      activity, causing reduction in activity frequency or intensity and even
      abstention. This syndrome is caused by elevation of the intra-compartmental
      pressure which leads to decreased tissue perfusion, thus ischemic damage to the
      tissue ensues. Chronic exertional syndrome is usually related to repetitive
      physical activity, usually in young people and athletes. The physical activity
      performed by the patient causes a rise in intra-compartmental pressure and
      thereby causes pain. The patient discontinues the activity and the pain subsides
      within minutes of rest. Chronic exertional syndrome is reported to occur in the
      thigh, shoulder, arm, hand, foot and gluteal region, but most commonly in the
      leg, especially the anterior compartment. The diagnosis of chronic exertional
      syndrome is primarily based on patients' medical history, supported by
      intramuscular pressure measurement of the specific compartment involved.
      Treatment of chronic exertional syndrome, especially the anterior and lateral
      compartment of the leg is mainly by surgery i.e. fasciotomy. If the patient is
      reluctant to undergo a surgical procedure, the conservative treatment is based on
      abstention from the offending activity, changing footwear or using arch support.
      However, the conservative approach is not as successful as surgical treatment.

PMID- 24450038
TI  - [How to choose a resident?].

PMID- 24450039
TI  - [The tragic fate of physicians].
AB  - Physicians and surgeons were always involved in revolutions, wars and political
      activities, as well as in various medical humanities. Tragic fate met these
      doctors, whether in the Russian prisons gulags, German labor or concentration
      camps, pogroms or at the hands of the Inquisition.

PMID- 24450040
TI  - Surgical procedures in pinniped and cetacean species.
AB  - Significant advances in veterinary diagnostic and surgical techniques have been
      made over the past several decades. Many of these advances, however, have not
      reached the field of marine mammal medicine. A number of limitations exist: risks
      of anesthesia, anatomical challenges, difficulties with wound closure,
      environmental constraints, equipment limitations, and perceived risks. Despite
      these limitations, surgical treatments have been successfully utilized in marine
      mammals. While surgery is performed in pinnipeds more frequently than in
      cetaceans, studies conducted in the 1960s and 1970s on dolphin sleep and hearing
      demonstrated that general anesthesia can be successfully induced in cetaceans.
      Since this pioneering work, a small number of successful surgeries have been
      performed in dolphins under both general anesthesia and heavy sedation. While
      these surgical procedures in pinnipeds and cetaceans have typically been limited
      to wound management, dentistry, ophthalmic procedures, fracture repair, and
      superficial biopsy, a number of abdominal surgeries have also been performed.
      Recently there have been pioneering successes in the application of minimally
      invasive surgery in marine mammals. Many of the anatomical challenges that almost
      prohibit traditional laparotomies in cetacean species and present challenges in
      pinnipeds can be overcome through the use of laparoscopic techniques. Due to the
      limited number of pinnipeds and cetaceans in captivity and, thus, the limited
      case load for veterinarians serving marine mammal species, it is vital for
      knowledge of surgical procedures to be shared among those in the field. This
      paper reviews case reports of surgical procedures, both traditional and
      laparoscopic, in pinnipeds and cetaceans. Limitations to performing surgical
      procedures in marine mammals are discussed and surgical case reports analyzed in
      an effort to determine challenges that must be overcome in order to make surgery
      a more feasible diagnostic and treatment option in the field of marine mammal
      medicine.

PMID- 24450041
TI  - Immunological evaluation of captive green sea turtle (Chelonia mydas) with
      ulcerative dermatitis.
AB  - Ulcerative dermatitis (UD) is common in captive sea turtles and manifests as skin
      erosions and ulcers associated with gram-negative bacteria. This study compared
      clinically healthy and UD-affected captive turtles by evaluating hematology,
      histopathology, immunoglobulin levels, and delayed-type hypersensitivity assay.
      Turtles with UD had significantly lower weight, reduced delayed-type
      hypersensitivity (DTH) responses, and higher heterophil:lymphocyte ratios. This
      study is the first to assay DTH in green turtles (Chelonia mydas) and suggests
      that UD is associated with immunosuppression.

PMID- 24450042
TI  - Retrospective study of morbidity and mortality of captive Iberian lynx (Lynx
      pardinus) in the ex situ conservation programme (2004-June 2010).
AB  - Medical records of 120 Iberian lynx (Lynx pardinus) from the captive breeding
      population (CBP), 96 of which were older than 1 wk old, were studied from January
      2004 to June 2010. From a total of 413 clinical signs recorded, it was possible
      to obtain a diagnosis in 258 (62.5%). Inappetence, skin wound, and vomiting had
      the highest incidence. Adult (2 to 6 yr old) and juvenile (1 wk to 1 yr old)
      animals accounted for most of the clinical signs. Vitamin D toxicosis and
      intraspecific trauma accounted for 55.4% and 15.1% of the clinical signs,
      respectively. Renal toxicosis due to the administration of supplements with an
      excess of vitamin D occurred in 2009 and affected a total of 39 individuals.
      Intraspecific trauma cases were predominantly observed from sibling aggression.
      Diet-related conditions consisted of sporadic cases of fatal salmonellosis,
      dermatophytosis, and gastrointestinal episodes. Suspected idiopathic epilepsy and
      femoral neck metaphyseal osteopathy were also observed. A total of 15 animals
      older than 1 wk old died including five vitamin D toxicosis cases and three
      juveniles due to intraspecific trauma. Mycobacterium bovis was found as a
      secondary infection in two animals that died from vitamin D toxicosis. Abortions,
      premature births, and stillbirths accounted for 12 mortalities, and 13 neonatal
      deaths due to maternal neglect or bacterial sepsis were observed. Data show that
      improvement of diet-related conditions is a key factor in preserving the health
      of animals in the CBP. Thus, the control of food and supplement composition,
      rabbit farm suppliers, and hygiene should be standardized and improved.
      Furthermore, data recording and diagnostic protocols should be standardized.

PMID- 24450043
TI  - Solubility of ammonium acid urate nephroliths from bottlenose dolphins (Tursiops
      truncatus).
AB  - Nephrolithiasis has been identified in managed populations of bottlenose dolphins
      (Tursiops truncatus); most of these nephroliths are composed of 100% ammonium
      acid urate (AAU). Several therapies are being investigated to treat and prevent
      nephrolithiasis in dolphins including the alkalization of urine for dissolution
      of nephroliths. This study evaluates the solubility of AAU nephroliths in a
      phosphate buffer, pH range 6.0-8.0, and in a carbonate-bicarbonate buffer, pH
      range 9.0-10.8. AAU nephroliths were obtained from six dolphins and solubility
      studies were conducted using reverse-phase high performance liquid chromatography
      with ultraviolet detection at 290 nm. AAU nephroliths were much more soluble in a
      carbonate-bicarbonate buffer, pH range 9.0-10.8 compared to phosphate buffer pH
      range 6.0-8.0. In the pH range 6.0-8.0, the solubility was 45% lower in potassium
      phosphate buffer compared to sodium phosphate buffer. When citrate was used along
      with phosphate in the same pH range, the solubility was improved by 13%. At pH 7
      and pH 8, 150 mM ionic strength buffer was optimum for dissolution. In summary,
      adjustment of urinary pH alone does not appear to be a useful way to treat AAU
      stones in bottlenose dolphins. Better understanding of the pathophysiology of AAU
      nephrolithiasis in dolphins is needed to optimize kidney stone prevention and
      treatment.

PMID- 24450044
TI  - Hematology and plasma biochemistry analytes in five age groups of immature,
      captive-reared loggerhead sea turtles (Caretta caretta).
AB  - Abstract: Blood samples of 85 immature, apparently healthy, captive-reared
      loggerhead sea turtles (Caretta caretta) were analyzed for 13 hematologic
      variables and total solids of 5 age groups (8, 20, 32, 44, and 56 mo old) and for
      20 plasma biochemical analytes of 4 age groups (20 to 56 mo old). Each individual
      turtle was sampled under similar conditions during a blood collection period of 3
      days. Hematologic analytes included packed cell volume, white blood cell (WBC)
      counts, WBC estimates, and leukocyte differentials. Biochemical analysis included
      albumin, alanine aminotransferase, alkaline phosphatase, amylase, aspartate
      aminotransferase, blood urea nitrogen, calcium, chloride, cholesterol, creatine
      kinase, creatinine, gamma glutamyltransferase, globulins, glucose, phosphorous,
      potassium, sodium, total bilirubin, total protein, total solids, and uric acid.
      In due consideration of small sample size in all five age groups, the results of
      hematologic and biochemical analysis were used to determine ranges for these
      analytes and to compare values among consecutive age groups. Several significant
      differences in some hematologic and biochemical variables were identified and
      need to be considered in the interpretation of blood work of immature, growing
      sea turtles in human care.

PMID- 24450045
TI  - Evaluating echocardiogram and indirect blood pressure results in male western
      lowland gorillas (Gorilla gorilla gorilla) during three phases of an anesthetic
      protocol.
AB  - Until the majority of the great ape population is trained for conscious cardiac
      evaluations, most individuals will require general anesthesia to perform
      echocardiograms. Within the veterinary community, concern exists that certain
      anesthetic protocols may exacerbate or artificially induce signs of cardiac
      disease. Because of potential cardiovascular effects, medetomidine has generally
      been used cautiously in patients with cardiac disease. The combination of
      ketamine and medetomidine is frequently used by many institutions because of its
      reversibility. To date, no published studies have obtained physiologic or
      echocardiographic parameters comparing different anesthetic protocols. In this
      study, with the use of seven adult male gorillas (Gorilla gorilla gorilla) with
      and without cardiac disease, echocardiographic and indirect blood pressure data
      during three phases of an anesthetic protocol were collected. The initial
      echocardiographic study was completed with ketamine/ medetomidine alone (5-7
      mg/kg, i.m., and 0.05-0.07 mg/kg, i.m., respectively); the second study was
      completed after the addition of sevoflurane inhalant anesthesia to this
      procedure; and the third study was completed after reversal of medetomidine by
      administration of atipamezole (5:1 with the medetomidine dose given at
      induction). Without exception, ejection fractions were 15-25% lower under
      anesthesia with medetomidine as compared to ejection fractions after
      administration of atipamezole. Indirect blood pressures were higher on ketamine/
      medetomidine, lower with addition of sevoflurane, and considerably lower after
      administration of atipamezole.

PMID- 24450046
TI  - Comparison of oral and intramuscular recombinant canine distemper vaccination in
      African wild dogs (Lycaon pictus).
AB  - A series of three doses of recombinant canary-pox-vectored canine distemper virus
      vaccine was administered at 1-mo intervals, orally (n = 8) or intramuscularly (n
      = 13), to 21 previously unvaccinated juvenile African wild dogs (Lycaon pictus)
      at the Wildlife Conservation Society's Bronx Zoo. Titers were measured by serum
      neutralization at each vaccination and at intervals over a period of 3.5-21.5 mo
      after the initial vaccination. All postvaccination titers were negative for
      orally vaccinated animals at all sampling time points. Of the animals that
      received intramuscular vaccinations, 100% had presumed protective titers by the
      end of the course of vaccination, but only 50% of those sampled at 6.5 mo
      postvaccination had positive titers. None of the three animals sampled at 21.5 mo
      postvaccination had positive titers.

PMID- 24450047
TI  - Physiologic effects of three different protocols of isoflurane anesthesia in
      captive brown brocket deer (Mazama gouazoubira).
AB  - This study evaluates the cardiorespiratory and physiologic effects of three
      different protocols of chemical restraint using isoflurane in captive brown
      brocket deer (Mazama gouazoubira). Six adult deer, two males and four females,
      aged 3-6 yr old and weighing 16.3 +/- 1.5 kg (mean +/- SD), were used. The deer
      were physically restrained and anesthetized using one of three protocols:
      protocol 1 (P1), anesthesia was induced directly with isoflurane using a facemask
      and maintained for 1 hr with isoflurane delivered by endotracheal tube; protocol
      2 (P2), oral premedication with midazolam was followed 1 hr later by induction
      and maintenance of anesthesia with isoflurane, as in P1; and protocol 3 (P3),
      intravenous anesthesia using a combination of ketamine, xylazine, and atropine
      was followed by isoflurane anesthesia, as in P1. Cardiorespiratory variables were
      recorded during physical restraint (TO); 5 min after intubation (T5); and every
      10 min during anesthesia (T15-T55). Venous and arterial blood gas analysis was
      conducted at TO (venous blood only), T15, T35, and T55. Data were analyzed by the
      appropriate statistical tests. P values < 0.05 were considered significant. Under
      P1, three deer regurgitated during induction and one of them died because of
      aspiration pneumonia. The end-tidal isoflurane concentration differed
      significantly between P1, P2, and P3 (2.6 +/- 0.2, 2.3 +/- 0.5, and 0.9 +/- 0.3%,
      respectively). Hypotension was observed during anesthesia (T15-T55). Respiratory
      acidosis occurred at all times and protocols, and pH was significantly lower in
      P1 compared to P2 and P3. Metabolic acidosis was also observed following physical
      restraint (T0-T35) in all protocols. The use of isoflurane via facemask for
      anesthesia induction is not a safe method in deer that are not premedicated.
      Isoflurane used alone or in combination with midazolam and ketamine-xylazine
      atropine combination causes hypotension and dose-dependent respiratory acidosis.

PMID- 24450048
TI  - Pansteatitis of unknown etiology associated with large-scale Nile crocodile
      (Crocodylus niloticus) mortality in Kruger National Park, South Africa:
      pathologic findings.
AB  - Annual mortality events in Nile crocodiles (Crocodylus niloticus) in the Olifants
      River Gorge in Kruger National Park, South Africa, were experienced between 2008
      and 2012, during which at least 216 crocodiles died. Live crocodiles were
      lethargic. Necropsy examination of 56 affected crocodiles showed dark yellow
      brown firm nodules in both somatic fat and the abdominal fat body. In all of the
      11 crocodiles submitted for histology, degenerative, necrotic, and inflammatory
      changes supported a diagnosis of steatitis in both fat types. Crocodiles are apex
      predators in this anthropogenically changed aquatic ecosystem that is used by
      humans upstream and downstream from the park for domestic, agricultural, fishing,
      and recreational purposes. This pathologic review of pansteatitis in crocodiles
      in the Olifants River system was part of a broad multidisciplinary research
      program. To date, no definitive causative agent has been identified.
      Epidemiologic evidence suggests that this event may have been a one-time event
      with long-standing repercussions on the health of the crocodiles. Pathologic
      findings are rarely documented in wild crocodilians. This study also reports on
      other conditions, including the presence of coccidian oocysts, capillarid and
      filaroid nematodes, digenetic trematodes, and pentastomes.

PMID- 24450049
TI  - Assessement of serum amyloid A levels in the rehabilitation setting in the
      Florida manatee (Trichechus manatus latirostris).
AB  - The acute phase protein serum amyloid A (SAA) has been previously shown to have
      value as a biomarker of inflammation and infection in many species, including
      manatees (Trichechus manatus latirostris). In the current study, results from an
      automated assay for SAA were used in a rehabilitation setting. Reference
      intervals were established from clinically normal manatees using the robust
      method: 0-46 mg/L. More than 30-fold higher mean SAA levels were observed in
      manatees suffering from cold stress and boat-related trauma. Poor correlations
      were observed between SAA and total white blood count, percentage of neutrophils,
      albumin, and albumin/globulin ratio. A moderate correlation was observed between
      SAA and the presence of nucleated red blood cells. The sensitivity of SAA testing
      was 93% and the specificity was 98%, representing the highest combined values of
      all the analytes. The results indicate that the automated method for SAA
      quantitation can provide important clinical data for manatees in a rehabilitation
      setting.

PMID- 24450050
TI  - Osteopathology in the feet of rhinoceroses: lesion type and distribution.
AB  - An estimated 1,170 white (Ceratotherium simum), black (Diceros bicornis), greater
      one-horned (Rhinoceros unicornis), and Sumatran (Dicerorhinus sumatrensis)
      rhinoceroses are kept in captivity worldwide, where they are a popular public
      attraction and serve important roles in education and conservation. Rhinoceroses
      in captivity are reportedly affected by a variety of foot conditions, including
      abscesses, nail cracking, and pododermatitis, but there are few studies reporting
      associated bony pathology in these species. This study aimed to describe
      osteopathology in rhinoceros feet and identify normal and abnormal osteologic
      features of rhinoceros feet. The metacarpal-tarsal and phalangeal bones from 81
      feet (67 skeletal specimens and 14 cadaveric feet), derived from 27 rhinoceroses
      of various species, were evaluated in the study (1 black, 11 white, 2 greater one
      horned, 3 Javan, 9 Sumatran, and 1 unknown). Bones were examined visually
      (skeletal specimens) or by computed tomography (cadaver specimens) for evidence
      of bony lesions. Of the 27 rhinoceroses examined, 22 showed some degree of bone
      pathology in at least one limb. Six broad categories of pathologic change were
      identified, with numbers in parentheses representing numbers of rhinoceroses with
      lesions in at least one limb/number of rhinoceroses examined: enthesopathy
      (20/27), osteoarthritis (15/27), pathologic bone remodeling (12/27), osteitis
      osteomyelitis (3/27), fracture (3/8), and subluxation (3/8). The frequency of
      pathologic changes in fore- and hind limbs was not significantly different. Most
      (91%) enthesopathies were observed on the proximal phalanges of the digits, and
      osteoarthritis was most common in the distal interphalangeal joints of the medial
      and lateral digits (32 and 26%, respectively). In addition to the pathology
      described, all examined rhinoceroses also had multiple small surface lucencies in
      the distal limb bones as an apparently normal anatomic feature. This study is an
      important first step in identifying both normal and pathologic features of
      rhinoceros feet and hopefully will thereby contribute to the improved knowledge
      and care of these species.

PMID- 24450051
TI  - Comparison of noninvasive blood pressure measurement techniques via the coccygeal
      artery in anesthetized cheetahs (Acinonyx jubatus).
AB  - Two indirect blood pressure measurement techniques, Doppler (DOP)
      sphygmomanometry and oscillometry, applied at the ventral coccygeal artery were
      compared with simultaneous direct blood pressure measurements at the dorsal pedal
      artery in 10 anesthetized, captive cheetahs (Acinonyx jubatus). The DOP method
      was moderately accurate, with relatively little bias (mean difference 3.8 mmHg)
      and 88.6% of the DOP systolic arterial pressure measurements being within 10 mmHg
      of the direct systolic arterial measurement. With the oscillometric (OM) method,
      89.2% of the mean arterial pressure measurements were within 10 mmHg of the
      direct measurement and had the least bias (mean difference 2.3 mmHg), 80.7% of
      the systolic measurements were within 10 mmHg of the direct measurement and had
      the second least bias (mean difference 2.3 mmHg), and 59% of the diastolic
      measurements were within 10 mmHg of the direct measurement and had significant
      bias (mean difference 7.3 mmHg). However, DOP showed relatively poor precision
      (SD 11.2 mmHg) compared with OM systolic (SD 8.0 mmHg), diastolic (SD 8.6 mmHg),
      and mean (SD 5.7 mmHg). Both techniques showed a linear relationship with the
      direct technique measurements over a wide range of blood pressures. The DOP
      method tended to underestimate systolic measurements below 160 mmHg and
      overestimate systolic measurements above 160 mmHg. The OM method tended to
      underestimate mean pressures below 160 mm Hg, overestimate mean pressures above
      160 mmHg, underestimate systolic pressures below 170 mmHg, overestimate systolic
      pressures above 170 mmHg, and underestimate diastolic pressures throughout the
      measured blood pressure range. Indirect blood pressure measurement using the
      ventral coccygeal artery, particularly when using an OM device for mean and
      systolic arterial pressure, may be useful in the clinical assessment of cheetahs
      when monitoring trends over time, but caution should be taken when interpreting
      individual values.

PMID- 24450052
TI  - Cross transmission of gastrointestinal nematodes between captive neotropical
      felids and feral cats.
AB  - Pathogen cross transmission between wildlife and domestic animals represents an
      extinction risk for wildlife; however, reliable verification is difficult to
      perform, and in some cases, it is even considered unlikely to be conducted. The
      aim of this work was to identify cross transmission of helminths between feral
      cats and captive wild felids at a zoological park in southeastern Mexico. Feces
      were collected from jaguars (Panthera onca), cougars (Puma concolor), ocelots
      (Leopardus pardalis), margays (Leopardus wiedii), and jaguarundis (Puma
      yagouaroundi). A flotation technique and macroscopic sieving were performed on
      the feces. Additionally, as part of the noxious fauna control program of the
      park, feral cats were captured and euthanized. To perform parasitologic studies,
      helminths from these animals were recovered. Toxocara cati and Trichuris
      campanula were shared by jaguarundis and feral cats. Ancylostoma sp. was found in
      jaguar and ocelot and Ancylostoma tubaeforme in feral cats. Additionally, during
      this study, a couple of jaguarundis died with clinical signs of trichuriasis.
      This is the first report of T. campanula in jaguarundi. Because feral cats roam
      freely in the park, transmission could occur from these vertebrates to wild
      felids. This study shows the risk that parasites represent to wild felids; a
      similar situation could be found in free-living species, especially in fragmented
      habitats that favor contact with domestic animals.

PMID- 24450053
TI  - The efficacy of intracoelomic fospropofol in red-eared sliders (Trachemys scripta
      elegans).
AB  - Intravenous anesthetic delivery in reptiles can be challenging. Current
      injectable techniques have varied induction/recovery times and anesthetic
      quality. This study hypothesized that intracoelomic administration of a new
      anesthetic, fospropofol, in turtles would result in dose-dependent anesthesia and
      respiratory depression. A two-part prospective trial using adult red-eared slider
      turtles (Trachemys scripta elegans) weighing 764 +/- 17 g was conducted to
      determine an effective anesthetic dose and to evaluate the anesthetic quality,
      duration, and respiratory effects of an efficacious dose. In part 1, six turtles
      were randomly administered 25-mg/ kg (low-dose [LD]) and 50-mg/kg (high-dose
      [HD]) fospropofol in a crossover design. Respiratory rate, immobility, and muscle
      relaxation scores were evaluated for 180 min. In part 2, eight turtles were
      administered HD fospropofol. Immobility and muscle relaxation (front and hind
      limb) scores and time to endotracheal intubation/extubation were evaluated until
      scores returned to baseline. In part 1, the LD group had significantly lower
      immobility and muscle relaxation scores versus the HD group over time (both P <
      0.05); scores were significantly elevated from baseline for 20-120 min and 15-180
      min, respectively (all P < 0.05). Although not significantly different between
      groups (P > 0.05), respiratory rate was significantly decreased from baseline
      from 10 to 120 min (all P < 0.05). In part 2, HD fospropofol decreased
      respiratory rate from 21.5 +/- 2.9 breaths/min to 0.1 +/- 0.1 breaths/min,
      similar to the results in part 1. Maximal reductions in mobility and front and
      hind limb motor tone occurred at 39.0 +/- 4.1, 30.8 +/- 3.6, and 24.0 +/- 3.6
      min, respectively. Intubation in 7/8 turtles occurred at 45.7 +/- 5.4 min and
      extubation at 147.0 +/- 23.2 min. However, 2/8 turtles showed prolonged
      anesthetic effects, requiring resuscitative efforts for recovery. Due to the
      unpredictable quality and duration of anesthesia with intracoelomic fospropofol,
      it should be used with caution for general anesthesia in red-eared sliders at the
      doses and administration route investigated.

PMID- 24450054
TI  - Characterization of integron-mediated antimicrobial resistance among Escherichia
      coli strains isolated from a captive population of Amur tigers in China.
AB  - The present study was undertaken to identify and characterize integrons and
      integrated resistance gene cassettes among multidrug resistant Escherichia coli
      isolates from a captive population of Amur tigers (Panthera tigris altaica) in
      China. In addition, the prevalence of antimicrobial resistance and class I
      integrons was assessed in E. coli strains (n = 61) isolated from a captive
      population of Amur tigers in Heilongjiang Amur Tiger Park, China. Among the
      isolates, 52.46% (32 of 61) were positive for intI1, but no isolates carried
      intI2 or intI3. Most isolates were susceptible to amoxicillin/clavulanic acid,
      aztreonam, and polymyxin B, while they also exhibited high incidence rates of
      resistance to ampicillin, doxycycline, chloramphenicol, tetracycline, and
      dihydrofolate reductase. Sequencing analysis revealed three gene cassettes, which
      encoded resistance to dihydrofolate reductase (dfrA15), dihydrofolate reductase
      (dfrA12), and adenyltransferase (aadA2). The gene cassette arrays dfrA15 (31%)
      and dfrA12-aadA2 (19%) were most prevalent among these isolates.

PMID- 24450055
TI  - Comparison of select hematology and serum chemistry analtyes between wild-caught
      and aquarium-housed lake sturgeon (Acipenser fulvescens).
AB  - Hematology and serum chemistry analytes were compared between wild-caught and
      aquarium-housed lake sturgeon (Acipenser fulvescens) to potentially improve
      understanding of medical issues in lake sturgeon. Blood samples were taken from
      30 lake sturgeon exhibited in 11 institutions in the United States and from 23
      experimentally stocked lake sturgeon caught in gill nets in the lower Genesee
      River in Rochester, New York, USA. For hematology, only segmented neutrophil
      count was significantly different, with wild-caught fish having a higher number
      of circulating neutrophils. For clinical chemistry analytes, chloride, uric acid,
      calcium, phosphate, glucose, aspartate aminotransferase, triglycerides, and
      creatine kinase were significantly different between the two cohorts. These
      differences are likely not clinically significant and are attributable to
      handling stress, variability in environmental parameters, or differences in
      nutritional status. This is the first report of hematology and serum chemistry
      values in aquarium-housed lake sturgeon and provides useful reference intervals
      for clinicians.

PMID- 24450056
TI  - Alfaxalone anesthesia in bullfrogs (Lithobates catesbeiana) by injection or
      immersion.
AB  - This project evaluated alfaxalone, a neurosteroid, as an anesthetic in bullfrogs.
      Eight adult bullfrogs (Lithobates catesbeiana), averaging 593 g (411-780 g) each,
      were used in a crossover design. Frogs were administered alfaxalone i.m. at 10,
      12, 15, or 17.5 mg/kg with a 1-wk washout. Following injection, time to
      recumbency, first limb movement following induction, and recovery were recorded.
      Respiratory rate was recorded following injection and then every 15 min following
      induction. Heart rate was assessed via Doppler every 15 min following induction.
      At 20 and 40 min, a 25-ga needle was inserted in a thigh muscle to assess
      response to noxious stimuli. Frogs were also immersed in 2 g/L of alfaxalone for
      up to 30 min and similarly assessed. At dosages of 10, 12, 15, and 17.5 mg/kg,
      the median time to recumbency was 15.4, 12.6, 12.3, and 6.6 min, respectively. At
      dosages of 10, 12, 15, and 17.5 mg/kg, median time to first limb movement was
      68.5, 77.5, 89.0, and 115 min, respectively. At dosages of 10, 12, 15, and 17.5
      mg/kg, median time to recovery was 90, 68.5, 124.5, 115 min, respectively.
      Following induction, at 10, 12, 15, and 17.5 mg/kg, median heart rate was 42, 40,
      40, and 42, respectively; and median respiratory rate was 44, 36, 29, and 35,
      respectively. Following administration of 10, 12, 15, and 17.5 mg/ kg, 8/8, 6/8,
      7/8, and 8/8 frogs, respectively, responded to needle insertion. None of the
      frogs dosed by immersion became anesthetized. Intramuscular alfaxalone produced
      immobilization in frogs but did not provide sufficient anesthesia to prevent
      response to noxious stimuli. Alfaxalone immersion at 2 g/L for 30 min did not
      produce immobilization or anesthesia.

PMID- 24450057
TI  - Electrocardiograms of bottlenose dolphins (Tursiops truncatus) out of water:
      habituated collection versus wild postcapture animals.
AB  - Electrocardiography (ECG) was performed on captured free-ranging bottlenose
      dolphins (Tursiops truncatus) during a health assessment exercise and compared
      with that of a Navy collection of dolphins habituated to handling out of water in
      order to assess possible cardiovascular impacts of capture and handling. Six-lead
      recordings (I, II, III, aVr, aVl, and aVf) in the frontal plane and direct thorax
      leads were collected from both groups, with a modified base-apex lead
      additionally employed with the Navy collection dolphins. Measured and calculated
      parameters included amplitudes of P, R, S, and T waves and total QRS complex; T:S
      and T:QRS ratios; heart rate; durations of P wave; QRS complex, PR, QT, and RR
      intervals; maximum minus minimum RR interval; ST segment elevation-depression;
      and mean electrical axis (MEA). Physiologically minor but statistically
      significant differences were detected in S wave amplitude, PR interval, QRS
      duration, and MEA. The PR interval, QRS duration, and S wave amplitude were
      slightly greater and the MEA oriented slightly rightward in wild postcapture
      dolphins compared to Navy collection dolphins. There were no differences in heart
      rate or maximum minus minimum RR interval, which serves as a proxy for the
      expected sinus arrhythmia of dolphins. The base-apex lead resulted in greater QRS
      amplitude than lead II, as expected for the category B ventricular activation of
      dolphins. The left-side direct thorax lead was more consistent than that of the
      right side. Clinically, ECG was a useful adjunct to auscultation and thoracic
      palpation for monitoring heart rate and rhythm and generated a record for
      archiving. Safe capture and handling protocols in place, under which dolphins are
      immediately returned to the water at progressive signs of distress, may make
      cardiovascular decompensation less likely to be detected by ECG. It appears that
      the dolphin cardiovascular system compensates suitably well to capture, as
      measured by ECG under the conditions of this study.

PMID- 24450058
TI  - Femoral head and neck excision arthroplasty in a leopard tortoise (Stigmochelys
      pardalis).
AB  - Cases of femoral head and neck excision arthroplasty are infrequently reported in
      reptiles, and details of surgical technique and clinical outcome in chelonia are
      lacking. An adult female leopard tortoise (Stigmochelys pardalis) was presented
      with chronic non-weight-bearing lameness of the left hind limb. Examination and
      radiography were consistent with coxofemoral luxation, and as a result of the
      chronic presentation, surgical intervention was recommended. A cranial approach
      to the joint via the prefemoral fossa afforded good surgical exposure. A
      depressed lytic acetabular lesion was noted during the procedure, postulated to
      be a result of abnormal wear from the luxated femoral head. A fiberglass prop was
      used during recovery to allow extension of the limb without full weight-bearing.
      Lameness persisted postoperatively, but limb usage significantly improved.

PMID- 24450059
TI  - Exercise-induced deep pectoral necrosis in white-headed pigeons (Columba
      leucomela).
AB  - Abstract: Two white-headed pigeons (Columba leucomela) developed deep pectoral
      myopathy 2 days after vigorous exercise associated with capture. Clinical signs
      included lethargy and an inability to raise the wings above the head. Gross
      pathology consistently revealed marked pallor and edema of the supracoracoideus
      muscle, and histopathology revealed severe myofiber degeneration. A further two
      white-headed pigeons presented 7 and 21 days postexercise with similar lesions.
      Treatment with fluids, physiotherapy, and analgesia was unsuccessful. This is the
      first report of deep muscle necrosis in Columbiformes.

PMID- 24450060
TI  - Conservative management of pneumothorax and pneumoperitoneum in two Florida
      manatees (Trichechus manatus latirostris).
AB  - Two distressed Florida manatees (Trichechus manatus latirostris) were reported to
      the Florida Fish and Wildlife Conservation Commission. The first animal was
      determined to be an abandoned, emaciated calf. The second animal was a nursing
      calf that had sustained watercraft-related trauma. Both animals were captured and
      transported to Tampa's Lowry Park Zoo, where diagnostic evaluations, including
      physical examinations, blood work, computed tomography (CT), and radiographs were
      performed. Radiograph and CT scans identified the presence of free air within the
      pleural and abdominal cavities of both animals. Based on the lack of substantial
      findings in the first animal and a rapid resolution of clinical signs in the
      second animal, both animals were managed conservatively. This report documents
      simultaneous pneumothorax and pneumoperitoneum, the associated clinical and
      diagnostic findings, and conservative medical management of these conditions in
      the Florida manatee.

PMID- 24450061
TI  - Batrachochytrium dendrobatidis in aquatic caecilians (Typhlonectes natans): a
      series of cases from two institutions.
AB  - Infection with the fungal organism Batrachochytrium dendrobatidis was documented
      in two captive populations of aquatic caecilians (Typhlonectes natans), including
      24 confiscated animals at the Bronx Zoo's Wildlife Health Center and two captive
      born animals at the Phoenix Zoo. The animals at the Bronx Zoo were asymptomatic,
      and infection was discovered during quarantine polymerase chain reaction
      screening. Both animals at the Phoenix Zoo were clinically ill, and
      Batrachochytrium dendrobatidis infection was confirmed in both animals, but it is
      unclear what role, if any, the infection played in the animals' clinical signs.
      All of the Bronx Zoo's caecilians were successfully cleared of infection by
      elevating to and then holding water temperatures at 32.2 degrees C (90 degrees F)
      for 72 hr. One animal at the Phoenix Zoo died before treatment could be
      instituted, and the second died despite treatment with a 0.01% itraconazole bath.
      Chytridiomycosis has only been very recently first reported in caecilians, and
      much remains unknown about its behavior in this amphibian order. This is the
      first published report of Batrachochytrium dendrobatidis infection in captive
      born caecilians and also the first describing details of treatment of
      chytridiomycosis in caecilians. It appears that raising tank temperature to 32.2
      degrees C for 72 hr is a safe and effective treatment for aquatic caecilians with
      chytridiomycosis.

PMID- 24450062
TI  - Medical management of pyometra in three red wolves (Canis rufus).
AB  - Pyometra is a serious, life-threatening disease of both domestic and non-domestic
      species often requiring ovariohysterectomy to preserve the life of the animal.
      Medical management of pyometra has been successful in domestic and non-domestic
      species, and the consideration of such treatment is of marked importance in a
      critically endangered species. Of the canids, the red wolf (Canis rufus) is
      second only to African hunting dogs (Lycaon pictus) in terms of the prevalence of
      both cystic endometrial hyperplasia and pyometra. In this report, three red
      wolves were medically managed for pyometra. Aside from vaginal discharge, none of
      the wolves exhibited clinical signs, nor were there reflective inflammatory
      changes in the laboratory findings. All wolves received standard treatment for
      pyometra, including prostaglandin F2alpha and antibiotic therapy, while one wolf
      was more aggressively managed with uterine lavage. Pyometra recurred in two of
      the treated wolves, while the most aggressively managed wolf continues to show
      ultrasonographic resolution 2 yr posttreatment. Aggressive medical management of
      pyometra should be considered a treatment option in certain red wolf females, as
      it may preserve the animal's reproductive potential.

PMID- 24450063
TI  - Uterine adenomyosis in southern three-banded armadillos (Tolypeutes matacus).
AB  - Uterine adenomyosis was diagnosed in five southern three-banded armadillos
      (Tolypeutes matacus) from four different zoological collections in North America
      between 1995 and 2012. Two cases were diagnosed after ovariohysterectomy and
      histopathologic evaluation of the uteri, and the remaining cases were identified
      incidentally at the time of postmortem examination. Animals ranged from 5 to 14
      yr of age at the time of diagnosis. Of armadillos diagnosed before postmortem
      examination, clinical signs included weakness, collapse, anemia, and vulvar
      discharge. Histopathologic evaluation of the uteri revealed well-developed,
      irregular endometrial glands extending into the myometrium and occasional
      hemorrhage within these glands. The two cases diagnosed antemortem were
      successfully treated with ovariohysterectomy. To the authors' knowledge, this
      condition has not been previously reported in Xenarthra, including armadillos.

PMID- 24450064
TI  - Respiratory disease in mountain gorillas (Gorilla beringei beringei) in Rwanda,
      1990-2010: outbreaks, clinical course, and medical management.
AB  - Between 1990 and 2010, 18 outbreaks of respiratory disease occurred in Rwanda's
      wild human-habituated mountain gorillas (Gorilla beringei beringei). An outbreak
      was defined as clinically observable respiratory illness involving at least one
      third of all the gorillas in a family group (> 30% morbidity) over the course of
      at least 7 days. Outbreaks lasted 2 wk to 4 mo and affected up to five different
      gorilla family groups, either concurrently or sequentially. An outbreak was
      considered over if no further clinical illness was observed in the same or
      another group for at least 1 mo. Clinical signs varied from nasal discharge,
      sneezing, and mild intermittent coughing (mild), to spasmodic coughing, lethargy,
      and partial anorexia (moderate), to dyspnea, tachypnea, respiratory distress,
      weakness, complete anorexia, and occasionally death (severe). Nearly every
      mountain gorilla group habituated for tourism or research in Rwanda experienced
      at least one outbreak, and they may be increasing in frequency. In the first 15
      yr of the review period 1990-2005, there were nine outbreaks involving 16 gorilla
      groups; in the last 5 yr of the review period, 2006-2010, there were nine
      outbreaks involving 11 groups. Although most gorillas recovered without
      treatment, 41 veterinary procedures were required to medically manage 35 severely
      ill individuals. Given the rise of mountain gorilla ecotourism in Rwanda, the
      possibility that respiratory disease results from contact with infected humans is
      of great concern, and both the etiology and epidemiology of this problem are
      active areas of research. The observed clinical signs, response to antimicrobial
      therapy among the sickest individuals, and postmortem findings are most
      consistent with viral upper respiratory tract infections complicated in some
      cases by secondary bacterial infections. The current gorilla visitation rules
      have been designed to minimize the risk of disease transmission between humans
      and wild human-habituated great apes.

PMID- 24450065
TI  - Retrospective serological investigation of bovine tuberculosis in two gemsbok
      (Oryx gazelle gazelle) and an onager (Equus hemionus onager).
AB  - In 1997 a 26-yr-old gemsbok (Oryx gazelle gazelle) died of bovine tuberculosis in
      a zoo. Three remaining gemsbok were administered the comparative tuberculin skin
      test repeatedly over a period of 5 mo. Two animals showed inconclusive results on
      the second test. All three gemsbok were euthanatized. Mycobacterium bovis was
      isolated from one of those with an inconclusive skin test result, whereas
      Mycobacterium fortuitum was detected in the other gemsbok. Eight years later, an
      onager (Equus hemionus onager) died of bovine tuberculosis. This animal had been
      kept in the same building as the gemsbok. Three herd mates were culled after
      administering the comparative tuberculin skin test. They were all nonreactors and
      produced no evidence of tuberculosis at postmortem examination. Retrospectively,
      using plasma samples collected from the gemsbok and onagers, three antibody
      tests, Elephant TB STAT-PAK, multiantigen print immunoassay (MAPIA), and dual
      path platform (DPP) VetTB (Chembio Diagnostic Systems Inc., Medford, New York,
      11763, USA), were used to assess their diagnostic value for these species. The M.
      bovis-infected gemsbok tested strongly positive by Elephant TB STAT-PAK at the
      time of euthanasia and 5 mo earlier when the skin test was negative. This animal
      was not antibody reactive in MAPIA and DPP VetTB. No M. bovis-specific antibody
      was detected in the other two gemsboks by any of the immunoassays. Among the
      onagers, Elephant TB STAT-PAK, MAPIA, and DPP VetTB revealed gradually increasing
      antibody response in the animal that died of bovine tuberculosis, but not in the
      three disease-free herd mates euthanatized. Seroconversion in the M. bovis
      infected onager was first noticed 5 yr before death when the tuberculin skin test
      was negative.

PMID- 24450066
TI  - Yolk embolism associated with trauma in vitellogenic sea turtles in Florida
      (USA): a review of 11 cases.
AB  - Case information and postmortem examination findings are presented for 11 adult
      female sea turtles in reproductive form that died in Florida, USA. All had
      abundant, large vitellogenic follicles, and most were either gravid or had
      recently nested. Species included six loggerheads (Caretta caretta) and five
      green turtles (Chelonia mydas). Identified proximate causes of death included
      falls or entrapment by obstructions on nesting beaches, burial under collapsed
      dunes, and other traumatic injuries of different causes. Evidence of yolk
      embolization was found in 10 cases and suspected in an 11th turtle. Ten turtles
      also had various amounts of free intracoelomic yolk. Although the effects of yolk
      embolization are uncertain at this time, precedence of pathologic importance in
      other species suggests that embolism may complicate traumatic injuries, including
      seemingly minor events.

PMID- 24450067
TI  - Eccrine carcinoma in the foot of an Asian elephant (Elephas maximus).
AB  - A case of eccrine carcinoma of the interdigital foot glands in a 39-yr-old female
      Asian elephant (Elephas maximus) from Zagreb Zoo is described. The tumor between
      the toenails of the right forefoot was surgically removed 3 yr before postmortem
      examination (2003), and the histopathologic diagnosis was compound eccrine
      carcinoma characterized with glandular tubular and papillary proliferations, mild
      cellular pleomorphism, proliferation of the myoepithelial cells with mucoid
      secretions, and necrosis. Immunohistochemistry revealed strong immunoreactivity
      to S-100 protein, estrogen, and high-molecular weight cytokeratin. This elephant
      also had chronic renal fibrosis with uremia.

PMID- 24450068
TI  - Unusual Turner syndrome mosaic with a triple x cell line (47,X/49,XXX) in a
      western lowland gorilla (Gorilla gorilla gorilla).
AB  - A 29-yr-old female western lowland gorilla (Gorilla gorilla gorilla) was
      evaluated for low fertility and a midterm abortion. Laboratory testing included
      karyotyping, which revealed an unusual mosaicism for Turner syndrome with Triple
      X (47,X/49,XXX). This appears to be the first report of Turner syndrome in a
      great ape. In humans, Turner syndrome occurs in approximately 1 in 3,000 females,
      with half of those monosomic for the X chromosome. A small proportion is mosaic
      for a triple X cell line (3-4%). In humans, Turner syndrome is associated with
      characteristic phenotype including short stature, obesity, a broad chest with
      widely spaced nipples, webbing of the neck, and anteverted ears. This individual
      gorilla is significantly shorter in stature than conspecifics and is obese
      despite normal caloric intake. Individuals with Turner syndrome should also be
      screened for common health issues, including congenital heart defects, obesity,
      kidney abnormalities, hypertension, hypothyroidism, and diabetes mellitus.
      Animals with decreased fertility, multiple miscarriages, fetal losses, unusual
      phenotypes, or a combination of these symptoms should be evaluated for genetic
      abnormalities.

PMID- 24450069
TI  - Intralesional vincristine use for treatment of squamous cell carcinoma in a puma
      (Puma concolor).
AB  - A 14-yr-old male puma (Puma concolor) was presented to the veterinary staff of
      the National Zoo in Malaysia for an auricular mass. Squamous cell carcinoma was
      diagnosed by histologic examination of a biopsy. Systemic administration of
      chemotherapy using vincristine (0.5 mg/m2 i.v. q. 7 days for six treatments) and
      prednisolone (2 mg/kg i.m. q. 72 hr x 7 days) caused side effects of vomiting,
      weight loss, and alopecia and did not improve the size or appearance of the
      tumor. Intralesional vincristine injections (0.2 mg q. 7 days for two treatments)
      and prednisolone (2 mg/kg i.m. q. 72 hr x 15 days) were administered, resulting
      in complete tumor regression after 14 days of treatment.

PMID- 24450070
TI  - Monteggia lesion in an Asian small-clawed otter (Aonyx cinerea).
AB  - A 10-yr-old female Asian small-clawed otter (Aonyx cinerea) presented with a
      history of right forelimb lameness. Antebrachial radiographs revealed a Monteggia
      lesion, classified by cranial radial head luxation and distal diaphyseal ulnar
      fracture. Open reduction with placement of an ulnar-radial positional screw was
      performed. The lateral collateral ligament was reconstructed using suture
      anchored by a condylar screw and bone tunnel in the radius. Reduction and proper
      implant placement was confirmed on postoperative radiographs. The ulnar-radial
      positional screw was removed 6 wk postoperatively to allow proper supination and
      pronation. Limb function was greatly improved at this time; however, a mild
      lameness was still observed. At 7 mo postoperatively, the otter was ambulating
      lameness-free. Radiographs documented proper joint reduction and stable condylar
      screw. At 32 mo postoperatively, the otter continued to exhibit normal
      ambulation.

PMID- 24450071
TI  - Squamous cell carcinoma of the anal sac in a spotted hyena (Crocuta crocuta).
AB  - A 25-yr-old spayed female spotted hyena (Crocuta crocuta) developed intermittent
      right pelvic limb lameness that persisted following conservative medical therapy.
      No obvious musculoskeletal lesions were noted on initial physical exam; however,
      spinal radiography was suspicious for possible intervertebral degenerative joint
      disease or discospondylitis. Despite prolonged medical therapy, the lameness
      progressed to minimal weight bearing and marked muscle atrophy of the right
      pelvic limb. Electromyography showed spontaneous activity in the muscles of right
      sciatic nerve distribution. Sensory and motor nerve conduction velocities in the
      right tibial and peroneal nerves were undetectable and markedly reduced,
      respectively. A magnetic resonance imaging (MRI) scan revealed a large, space
      occupying mass on the right side of the sacrum and pelvis. Antemortem fine-needle
      aspiration of the mass and postmortem histopathology resulted in diagnosis of a
      high-grade squamous cell carcinoma of the anal sac. Squamous cell carcinoma of
      the anal sac is very rare in domestic dogs and previously unreported in spotted
      hyenas.

PMID- 24450072
TI  - Sternal osteosarcoma in a blue crane (Anthropoides paradiseus).
AB  - A previously healthy, adult male blue crane (Anthropoides paradiseus) became
      peracutely distressed and ataxic. Examination revealed hemoptysis and a large
      mass associated with the cranial aspect of the sternum (keel). The patient died
      before treatment could be initiated. Gross necropsy revealed a large, hemorrhagic
      mass originating from the cranial aspect of the keel and extending into the
      cranial coelomic cavity. Histopathology confirmed the mass as an osteosarcoma.
      This is the first known report of an osteosarcoma in any crane species.

PMID- 24450073
TI  - Fat-soluble vitamin and mineral comparisons between zoo-based and free-ranging
      koalas (Phascolarctos cinereus).
AB  - As part of a health investigation on koalas at San Diego Zoo, serum samples were
      analyzed from 18 free-ranging and 22 zoo-based koalas, Phascolarctos cinereus.
      Serum concentrations of calcium, chloride, cobalt, copper, iron, magnesium,
      manganese, molybdenum, phosphorus, potassium, selenium, sodium, zinc, and
      vitamins A, E, and 25(OH)D3 were quantified. Calcium, chloride, molybdenum,
      selenium, and vitamin E concentrations were significantly higher in zoo-based
      koalas than in free-ranging koalas, whereas magnesium, manganese, phosphorus, and
      zinc concentrations were significantly higher in the free-ranging koalas. No
      significant differences were found between genders. The results from this study
      will help to establish a starting point for determining target circulating
      nutrient concentrations in koalas.

PMID- 24450074
TI  - Effect of perphenazine enanthate in Pyrenean chamois (Rupicapra pyrenaica).
AB  - Perphenazine enanthate was used to allow adaptation to captivity in 11 Pyrenean
      chamois (Rupicapra pyrenaica). At the time of capture, all animals received 0.10
      mg/kg of acepromazine maleate and 2.5 mg/kg of perphenazine enanthate
      intramuscularly. The effect was evaluated by means of three behaviors: alertness,
      defecation, and flight distance. The tranquilization and lack of fear of humans
      of all animals were determined and the usefulness of this long-acting
      tranquilizer for chamois adaptation to captivity was confirmed.

PMID- 24450075
TI  - Clinical and diagnostic imaging findings in an Italian wolf (Canis lupus
      italicus) with discospondylitis.
AB  - An adult male Italian wolf (Canis lupus italicus) was presented with an abnormal
      gait. Neurologic examination showed thoracic kyphosis, paraparesis, decreased
      proprioception in the pelvic limbs, and normal spinal reflexes. Neurologic
      symptoms suggested a thoracolumbar spinal cord lesion. Pathologic findings
      included leukocytosis. Spinal radiographs revealed ventral spondylosis of
      T4/T5/T6, a poorly defined intervertebral disc space, and mild lysis of the
      vertebral margins. Multiple metallic foreign bodies were seen in the thoracic
      wall. Magnetic resonance imaging of the spine detected increased signal intensity
      on fluid sensitive sequences of the vertebral bodies, the intervertebral disc,
      and surrounding soft tissues. These findings were interpreted as active
      discospondylitis at T4/T5. Medical therapy included antibiotic and analgesic
      treatment as well as movement restriction. Follow-up at 4 wk showed significant
      clinical and radiologic improvement. Discospondylitis should be included in the
      differential diagnosis in wolves with paresis.

PMID- 24450076
TI  - Isolation of Aeromonas hydrophila in the respiratory tract of wild boar:
      pathologic implications.
AB  - Aeromonas hydrophila has been repeatedly reported as an animal pathogen. This
      study describes a case of a wild boar piglet in Spain with severe purulent
      pneumonia caused by A. hydrophila. To confirm the presence of A. hydrophila in
      the respiratory tract of wild boars from the same region, lung samples from 34
      adult hunted animals and nasal samples from 12 live animals were collected and
      cultured in selective medium. Lung lesions were studied in hunted wild boars to
      determine the presence of A. hydrophila and to assess its role as a possible
      respiratory pathogen in wild boars. A. hydrophila was isolated in 10.87% of the
      animals studied (8.82% of the dead animals and 16% of the live animals). However,
      its presence in the lungs of adults could not be correlated with the lesions
      found. Thus, the role of A. hydrophila as a respiratory pathogen is likely to be
      influenced by other factors, such as age, immunologic status, or coinfection with
      other pathogens. As a zoonotic pathogen, the presence of A. hydrophila in wild
      boars may pose a potential risk to people who consume their flesh.

PMID- 24450077
TI  - Intestinal coccidioidomycosis in a red coachwhip snake (Masticophis flagellum
      piceus).
AB  - An adult female, wild-caught red coachwhip snake (Masticophis flagellum piceus)
      was euthanized at the Phoenix Zoo due to severe neurologic signs. Necropsy and
      histopathology revealed an invasive liposarcoma of the vertebral column, which
      likely caused the neurologic signs. Histology of the small intestine revealed a
      granuloma with intralesional yeasts morphologically compatible with the genus
      Coccidioides. The diagnosis of coccidioidomycosis was confirmed with
      immunohistochemistry staining. Coccidioides posadasii is endemic to Arizona and
      is an important cause of disseminated fungal infections in mammals in this
      region. This is the first known report of intestinal coccidioidomycosis in a
      veterinary species and the second report of coccidioidomycosis in a reptile.

PMID- 24450078
TI  - Mycobacterium intracellulare infection in a capybara (Hydrochoerus hydrochaeris).
AB  - This report describes the first case of Mycobacterium intracellulare infection
      with typical granulomatous lesions of mycobacteriosis in a capybara (Hydrochoerus
      hydrochaeris). The individual was a captive-bred young female, part of the
      control group of an experimental study on stress. Multiple granulomatous lesions
      were detected in a mesenteric lymph node of this young female. Mycobacterial
      infection was confirmed by bacteriologic culture and molecular identification
      methods. Clinical lesions were characterized by histopathology.

PMID- 24450079
TI  - Intrauterine fetal death with subsequent quill exfoliation and dissemination in a
      North American porcupine (Erethizon dorsatum).
AB  - An adult female, wild North American porcupine (Erethizon dorsatum) presented
      with bilateral cataracts and naso-ocular discharge. A pregnancy was identified by
      radiography with a near-full-term fetus, which was delivered stillborn 4 wk later
      with hard, developed quills. At that time, a repeated examination and further
      imaging, including computed tomography, demonstrated a uterine mass that was
      identified as a choriocarcinoma following ovariohysterectomy. Additionally,
      numerous exfoliated quills were discovered throughout the abdomen, most of which
      were removed during the surgical procedure. Ultimately, development of
      peritonitis despite medical care led to the porcupine's death. Necropsy confirmed
      a wide migration of the quills with extensive serosal adhesions and granulomas
      affecting liver, lungs, urinary bladder, kidneys, and gastrointestinal tract.

PMID- 24450080
TI  - Acute phase protein and protein electrophoresis values for captive Grant's zebra
      (Equus burchelli).
AB  - Grant's zebra (Equus burchelli) are commonly kept in zoos and are subject to
      routine health monitoring and research studies. Recently, assays for acute phase
      proteins (APP) have been described in many wildlife species, and specific assays
      for serum amyloid A (SAA) have been well validated and studied in horses (Equus
      ferus caballus), in which it serves as a major APP. In the present study, serum
      samples from 26 Grant's zebra were subject to analysis by using assays for SAA,
      haptoglobin (HP), and protein electrophoresis. Reference intervals were
      calculated by using the robust method: SAA 1.8-31.4 mg/L and HP 0.37-1.58 mg/ml.
      Significant differences in SAA and HP were observed in clinically abnormal zebra;
      in some cases, these differences were marked and were noted in the absence of
      abnormal values for protein electrophoretic fractions. These data indicate that
      APP may be a valuable and sensitive tool in monitoring inflammation in this
      species.

PMID- 24450081
TI  - Pyloric trichobezoar in a Canadian lynx (Lynx canadensis).
AB  - An adult female Canadian lynx (Lynx canadensis) was presented with a 3-wk history
      of anorexia and lethargy. Initial examination and diagnostics did not provide a
      diagnosis. The lynx continued to demonstrate vague clinical signs, including
      anorexia and an abnormal gait. During follow-up immobilizations 2 wk later, a
      barium gastrointestinal study revealed a pyloric obstruction. Abdominal
      exploratory surgery was elected, and a gastrotomy and an enterotomy of the
      proximal duodenum were performed to remove the pyloric obstruction. The
      obstruction was determined to be a trichobezoar. Fleas, a likely cause of hair
      ingestion through grooming, were noted during surgical preparation. The lynx made
      a full recovery from surgery. Reoccurrence of the trichobezoar was prevented
      after surgery with the use of monthly flea control and three times a week
      hairball laxative.

PMID- 24450082
TI  - Antemortem diagnosis and successful management of noncompressive segmental
      myelopathy in a Siberian-Bengal mixed breed tiger.
AB  - A 10-yr-old female spayed mixed breed tiger presented for a 9-day history of
      acute and nonprogressive paralysis of the pelvic limbs. Magnetic resonance
      imaging revealed a lesion suggestive of fibrocartilaginous embolic myelopathy
      with regional spinal cord edema, decreased disk signal intensity at L2-L3, and
      mild intervertebral disk protrusion at L1-L2 and L2-L3. Cerebral spinal fluid
      analysis showed no overt evidence of infection or neoplasia. Medical therapy was
      instituted, including corticosteroids and gastroprotectants as well as nursing
      care and physical therapy. The tiger began showing clinical improvement 2 wk
      after initiating treatment, progressing to the point where the animal was
      standing and intermittently walking. Three months after diagnosis, the tiger had
      regained muscle strength of its hind limbs and walked regularly with improving
      coordination. This case is the first report of antemortem diagnosis and
      successful medical management of suspected fibrocartilaginous embolic myelopathy
      in a large exotic felid.

PMID- 24450083
TI  - Mediastinal teratoma in a free-ranging American black bear (Ursus americanus).
AB  - A 2.75-yr-old female American black bear (Ursus americanus) was found emaciated
      and unable to rise. It was euthanized due to the perceived poor prognosis. An
      approximately 18 x 8 x 10-cm, multiloculated, well-demarcated mass that extended
      from the bifurcation of the trachea, laterally displacing the lung lobes and
      caudally displacing the heart. The mass contained fibrous connective tissue,
      cartilage, bone, nervous tissue, smooth muscle, and a variety of epithelial
      structures. A mediastinal teratoma was diagnosed based on the microscopic
      features of the neoplasm.

PMID- 24450084
TI  - Detection and characterization of a Trichomonas isolate from a rehabilitated bald
      eagle (Haliaeetus leucocephalus).
AB  - A hatching-year bald eagle (Haliaeetus leucocephalus) was presented for clinical
      examination after being found unable to fly. Upon admission, routine wet-mount
      microscopy detected no trichomonads. Five months later, oral cavity inspection
      found no abnormalities, but the eagle was swabbed for research on trichomonosis
      in maritime birds. The swab was used to inoculate an InPouch TF culture and
      trichomonads were visible within 24 hr. Genotyping (ITS) revealed a Trichomonas
      isolate that was 100% identical to an isolate from a bearded vulture (Gypaetus
      barbatus) from the Czech Republic. The eagle was treated with metronidazole (50
      mg/kg q 12h PO for 5 consecutive days). Following treatment, the eagle was
      swabbed and the inoculated InPouch TF culture was monitored daily for 1 wk. No
      trichomonads were observed. Rehabilitation centers interested in surveillance
      should consider combining the InPouch TF technique with clinical inspection of
      live birds to confirm trichomonosis and for future research.

PMID- 24450085
TI  - Isolation and RFLP genotyping of Toxoplasma gondii from the mongoose (Herpestes
      auropunctatus) in Grenada, West Indies.
AB  - Little is known of the genetic diversity and epidemiology of Toxoplasma gondii
      infection in wildlife in Caribbean Islands. The prevalence and genetic diversity
      of T. gondii in mongooses (Herpestes auropunctatus) was investigated. During 2011
      and 2012, 91 mongooses were trapped in different parts of Grenada, bled,
      euthanized, and examined at necropsy. Antibodies to T. gondii were found in 27
      mongooses tested by the modified agglutination test (cut-off titer 25). Muscles
      (heart, tongue, neck) of 25 of the seropositive mongooses were bioassayed for T.
      gondii infection in mice. Viable T. gondii was isolated by bioassay in mice from
      four mongooses with MAT titers of 1:50 in two, 1:200 for one, and 1:400 for one
      mongoose. The four T. gondii isolates were further propagated in cell culture.
      Strain typing of T. gondii DNA extracted from cell-cultured tachyzoites using the
      10 PCR-restriction fragment length polymorphism (RFLP) markers SAG1, SAG2, SAG3,
      BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico revealed one isolate belongs to
      the Type III (ToxoDB #2) lineage, two to ToxoDB#7 lineage, and one to the ToxoDB
      #216 lineage. This is the first report of T. gondii isolation and genotyping in
      H. auropunctatus worldwide.

PMID- 24450086
TI  - Survey of antibodies to Leishmania spp. in wild canids from Pennsylvania and
      Tennessee.
AB  - Visceral leishmaniasis (VL) is a zoonosis with worldwide distribution. Infections
      with the Leishmania donovani complex, including Leishmania infantum, cause the
      VL. Domestic dogs are the most important reservoir host for human VL, and wild
      canids are also susceptible. In the United States, infections with L. infantum
      are common in the foxhound dog breed. Little information is available regarding
      L. infantum in wild canids in the Unites States. Sera from 11 foxes and 256
      coyotes originating in Pennsylvania and Tennessee (USA) were tested for
      antibodies to visceralizing Leishmania spp. with rapid immunochromatographic
      dipstick assays, which utilize recombinant antigen K39. Anti-Leishmania spp.
      antibodies were found in 5 of 267 (1.9%) of wild canids from Pennsylvania,
      including four coyotes and one red fox. These results suggest that wild canids
      are exposed to Leishmania spp. at a low level in the United States.

PMID- 24450087
TI  - Clinical challenge: systemic Rhizopus microsporus infection with renal cavitation
      in a grey seal (Halichoerus grypus).

PMID- 24450088
TI  - Fragile load. An elderly patient must be handled with care.

PMID- 24450089
TI  - Rewards. Finding the treasure in mundane calls.

PMID- 24450090
TI  - Ten steps to create safer systems. Here are EMS 2020's best pratices for
      protecting patients and personnel.

PMID- 24450091
TI  - The impaired immune system. How is it suppressed, and what does it mean for EMS?

PMID- 24450092
TI  - Lost in translation. What happens when patients don't speak English?

PMID- 24450093
TI  - Health of individual insurance markets likely to vary by state.

PMID- 24450094
TI  - Making ACA work seen as key to elections.

PMID- 24450095
TI  - Payer, state issues slow dual-eligible reform.

PMID- 24450096
TI  - Rise in measles and other infectious diseases has U.S. public health experts on
      alert.

PMID- 24450097
TI  - Spare us the complaints about healthcare "redistribution".

PMID- 24450098
TI  - Improve care through outcomes reporting.

PMID- 24450099
TI  - Buyers should demand price transparency.

PMID- 24450100
TI  - Stark law complicated by "smart lawyers" finding loopholes. Interviewed by Joe
      Carlson.

PMID- 24450101
TI  - Largest skilled-nursing companies. Ranked by net revenue.

PMID- 24450102
TI  - [Nonspecific reacting materials that interferes tacrolimus assay by ACMIA].
AB  - We report two cases of falsely elevated levels of Tacrolimus (TAC) measured by
      affinity column mediated immunoassay (ACMIA). Potential reasons for this are
      herein explored. Patient 1, a post-renal transplantation patient, was treated by
      TAC, while patient 2, a patient with rheumatoid arthritis, was not. TAC levels
      measured by ACMIA of patients 1 and 2 were greater than 40 and 20 ng/ml,
      respectively. In patient 2, rheumatoid factor (RF) levels were constantly higher
      than 1,000 IU/ml, and levels of TAC were shown to be correlated with RF. Results
      of immunoglobulin adsorption tests and gel filtration suggested that the false
      positivities for TCA were induced by IgG of patient 1 and IgM of patient 2. After
      the addition of anti-TAC antibody, levels of TAC decreased to an undetectable
      range in both cases. TAC levels also became undetectable after the addition of
      MAK33-Framework IEP in patient 1 and IIR in patient 2. In patient 2, the addition
      of HBR-1 and MAK absorbent prevented the false positive phenomenon. In both
      cases, human anti mouse antibodies (HAMAs) reacted to anti-TAC mouse monoclonal
      antibodies within the reagent and produced falsely elevated results. These
      results were inhibited by MAK33-Framework IEP binding to the hyper-variable
      region of immunoglobulin; therefore, the causative agent of this phenomenon in
      patient 1 was likely an anti-idiotype antibody against the mouse monoclonal anti
      TAC antibody used in the assay. Furthermore, a close relationship between
      measured levels of TAC and RF, along with the finding that the addition of HBR-1
      and IRR prevents false positive results, suggests that RF produced false positive
      results through IgM-HAMA activity in patient 2. These data indicate that false
      positive results of TAC can be due to the presence of HAMAs with different
      specificities.

PMID- 24450103
TI  - [Evaluation of the latex turbidimetric immunoassay for CK-MB protein].
AB  - CK-MB protein is an important marker for the diagnosis of acute coronary
      syndromes. In the present study, we evaluated the basal performance of recently
      developed CK-MB mass kit "L-type wako CK-MB mass". Within-run and between-day
      precision were obtained with 1.4-4.7% and 2.7-5.2%, respectively. Diluted
      linearity and lower limit of detection were obtained with 180.0 ng/mL and 2.1
      ng/mL, respectively. Zone phenomenon was able to detect until 25,600.0 ng/mL.
      Analysis of interferent showed that only CK-BB positively influenced the assay
      results. CK-MB protein levels decreased to 82% at 72 hours in the room
      temperature, but it was stable at 4 degrees C and -20 degrees C. The correlation
      coefficient(r) between this assay and conventional assay was 0.999. However,
      discrepancy of the two cases was observed in the comparison between the two
      methods. In the case 1, CK isoenzyme analysis using electrophoresis indicated
      that CK-MB was not present and absorption test showed a 68% absorption effect of
      CK-MB protein values not by anti human IgG, anti human IgA, and animal serums,
      but anti human IgM. In the case 2, CK isoenzyme analysis indicated that there is
      not only CK-MB but CK-BB. CK-MB protein values between the two methods were
      fitted after decreasing CK-BB. Thus, Value discrepancy for CK-MB protein was
      resulting from IgM and CK-BB. We have to pay attention to such phenomenon when
      detecting an unlikely higher levels that could not be explained by clinical
      information.

PMID- 24450104
TI  - [A case of MM1+2 Creutzfeldt-Jakob disease with a longitudinal study of EEG and
      MRI].
AB  - We report a case of definite MM1 + 2 sporadic Creutzfeldt-Jakob disease (sCJD). A
      66-year-old woman was admitted to our hospital with memory disturbance and
      disorientation for three months. On admission she presented a progressive
      cognitive insufficiency. Electroencephalography (EEG) revealed a frontal
      intermittent rhythmical delta activity (FIRDA) and the brain magnetic resonance
      imaging (MRI) showed high signal intensities in cerebral cortex on diffusion
      weighted images (DWI). After four months from the onset, she reached the akinetic
      mutism state followed by myoclonus. Follow up examination revealed that periodic
      synchronous discharge (PSD) was found in EEG, and DWI revealed enlargement of
      high signal intensity lesions in cerebral cortex. At seven months from the onset,
      PSD and high signal intensities of cortex became unclear with disappearance of
      myoclonus, and brain white matter lesions were evident on MRI. Serial studies of
      EEG and MRI revealed that PSD generalized from frontal lobe dominant pattern,
      while high signal intensity lesions of cortex diffusely increased on DWI. At ten
      months from the onset patient died. Pathological examination in brain showed
      moderate and diffuse neuronal cell loss and gliosis in cerebral cortex
      corresponding with DWI changes. The genotype at codon 129 of the prion protein
      (PrP) was homozygous methionine (MM) and the type of protease-resistant PrP
      (PrPres) was the mixed type of 1 and 2 in Western blot analysis. It has been rare
      to analyze the changes of EEG and MRI in the entire stage and to investigate
      pathological finding in the case of sCJD-MM1 + 2. A longitudinal examination of
      EEG and MRI is useful for early diagnosis of CJD. Also we could correlate these
      findings with clinical and histopathological phenotype.

PMID- 24450105
TI  - [DNA polymorphisms].
AB  - Genetic variations, including single nucleotide polymorphisms (SNP), variable
      numbers of repetitive sequences such as microsatellite polymorphisms, and small
      insertion-deletion polymorphisms (INDELs), have been reportedly associated with
      various diseases. SNP is just a single base change in a DNA sequence, with the
      usual alternative of two possible nucleotides at a given position. Microsatellite
      polymorphisms are variations in the number of short nucleotide repeats observed
      at microsatellite loci. INDELs are small insertions and deletions ranging from 1
      to 10,000 bp in length. Another variation in the human genome is that of genomic
      structural variants, including copy number variations (CNVs). The CNVs involve
      gains or losses of several to hundreds of kilobases of genomic DNA among
      phenotypically normal individuals and at least 291,801 CNV regions have been
      identified. Recent studies have described the associations of CNVs with various
      common disorders, especially with mental illness. In order to make an extensive
      public catalog of human genetic variations, including SNPs and structural
      variants, and their haplotype contexts, the 1,000 Genomes Project has been
      performed with international collaboration using the genomes of about 2,500
      unidentified people from about 25 populations around the world with next
      generation sequencing technologies. This resource will support genome-wide
      association studies and other medical research studies. In this review, we focus
      on HapMap and the association between the various genetic variations and
      diseases.

PMID- 24450106
TI  - [Analysis of single nucleotide polymorphisms (SNPs)].
AB  - Single nucleotide polymorphisms (SNPs) are DNA sequence variations occurring when
      a single nucleotide in the genome differs in paired chromosomes. Some SNPs in the
      coding region change the amino acid sequence of a protein, and others in the
      coding region do not affect the protein sequence. SNPs outside the coding region
      may also affect transcription factor binding, gene splicing, or mRNA degradation.
      With or without such impacts on the biological function of gene products, SNPs
      are strongly useful as markers to examine linkage disequilibrium and to explore
      genetic polymorphisms in the research of population genetics and medical science.
      Knowledge about SNPs is expected to help in identifying susceptibility genes for
      complex diseases, drug susceptibility genes, and histocompatibility genes for
      transfusion or transplantation. Recent breakthroughs in DNA technology, such as
      high-throughput universal SNP microarrays and next-generation sequencers, have
      made it possible to carry out comprehensive analyses of DNA at the whole genome
      level, resulting in the implementation of a genome-wide association study(GWAS).
      In GWAS, SNPs are used as high-solution markers in gene mapping related to
      diseases versus normal traits. The outcomes of GWAS provide a number of
      supportive findings for the promotion of personalized medicine based on genome
      informatics. This article presents a review of SNP analysis with respect to its
      scientific significance and current progress.

PMID- 24450107
TI  - [Pharmacogenomics].
AB  - Personalized medicine based on pharmacogenomics is being developed at the
      clinical stage. Pharmacogenomics involve the study of the role of genomic
      variation in individual variations in drug response, a phenotype that varies from
      potentially life-threatening adverse drug reactions to an equally serious lack of
      therapeutic efficacy. These developments in pharmacogenomics are strongly
      supported by marked innovations in genetic analyses. The molecular targets of
      clinical pharmacogenomics are the genetic and genomic factors of both the patient
      and the pathological organ. Molecular target drugs have become standard
      treatments in cancer therapy. The efficacy of these drugs can be predicted by
      characterization of the molecular target before administration. Such
      characterization for treatment guidance is called companion diagnostics.
      Companion diagnostics are tests that are intended to assist physicians in making
      treatment decisions for their patients based on the best response to therapy.
      Moreover, companion diagnostic co-development can highly change the drug
      development process and clinical trials by significantly yielding safer drugs
      with better therapeutic efficacy in a faster, more cost-effective way. However,
      many companies are interested in the development of companion diagnostics for
      targeted therapies in specific fields such as cancer. Thus, there are currently
      no potential companion diagnostics for common diseases. As common diseases are
      multifactorial, multiplex testing is required to predict therapeutic efficacy.
      The development of multiplex companion diagnostics is anticipated for the
      expansion of personalized medicine.

PMID- 24450109
TI  - [Molecular tests of mitochondrial genome].
AB  - Mitochondria are considered to have originated from the symbiotic invasion of
      bacteria with aerobic ATP production into pro-eukaryotic cells about two billion
      years ago. For this evolutionary reason, mitochondria have maintained their own
      genome. Mitochondrial DNA is circular and is inherited maternally. Thus,
      mitochondrial DNA has characteristics different from nuclear DNA. Human
      mitochondrial DNA is small, about 16.5kbp in length, and encodes only two rRNAs,
      22 tRNAs, and 13 proteins. However, the mitochondrial genome is essential for
      normal integrity of the mitochondrial electron transfer system (or respiratory
      chain). The electron transfer system is not only responsible for about 90% of
      cellular ATP production but is also closely linked to the metabolism of fatty
      acids, amino acids, and nucleic acids. In addition, its lack of integrity can
      cause overproduction of reactive oxygen species. Therefore, mutations of the
      mitochondrial genome are currently believed to be involved in many common
      diseases as well as classical mitochondrial neuromyopathies. Accordingly, more
      researchers have begun to take an interest in the association of mitochondrial
      DNA polymorphisms with aging and common diseases such as cancer, diabetes,
      neurodegeneration, and so on.

PMID- 24450108
TI  - [HLA genotyping for molecular epidemiological analysis of humans].
AB  - The major histocompatibility complex (MHC) gene family in humans is termed the
      human leukocyte antigen (HLA) locus, and is one of the most polymorphic loci in
      the human genome. HLA and related genes play many important roles in the immune
      system. HLA matching is critical for the success of organ and hematopoietic stem
      cell transplantation. Additionally, HLA genes and proteins are associated with
      autoimmunity, immunity to infections, tumor development, and adverse drug
      reactions (ADR). For matching donor and recipient HLA types and to understand the
      role played by the HLA in disease development, lymphocyte cytotoxicity tests
      (LCT) were developed by Dr. Terasaki in the 1960s. This serological typing
      method, which was in use until recently, is now no longer used and has been
      replaced by DNA-based typing methods such as PCR-SSP (sequence-specific primers),
      PCR-rSSO(reverse sequence-specific oligonucleotide probes), and PCR-SBT (sequence
      based typing). In the future, the current HLA-typing methods will be replaced by
      faster, more detailed and more cost-effective methods such as next-generation
      sequencing (NGS). In this review, we focus on the past and present methods of HLA
      typing, and the role of the HLA in various diseases.

PMID- 24450110
TI  - [Circadian clocks and lifestyle-related diseases].
AB  - Recent studies have demonstrated relationships between the disturbance of
      circadian rhythm and the development of lifestyle-related diseases. First,
      epidemiological studies showed that rotating shift workers are more likely to
      develop obesity, hypertension, type 2 diabetes, coronary heart disease, and
      cancers than day shift employees. In addition, mice with their circadian rhythm
      chronically impaired by alteration of the light-dark cycle also develop such
      diseases. Furthermore, both the genotypes and genetic modifications of the clock
      genes are associated with the development of lifestyle-related diseases in humans
      and mice, respectively. Finally, circadian clocks in peripheral tissues are
      impaired in both patients with type 2 diabetes and obese diabetic mice, probably
      not due to metabolic abnormalities, but to the lifestyle, aging, and/or genetic
      factors. Thus, disturbance of the circadian rhythm is an important cause of
      lifestyle-related diseases, and therefore the circadian clocks are attractive
      therapeutic targets for preventing and treating these conditions.

PMID- 24450111
TI  - [Chair remarks of the symposium. "Updated learning from experts in laboratory
      disciplines"].
AB  - Clinical laboratories should collect and keep updated information on issues
      related with quality management. This symposium was undertaken for an expert
      review of the updates in laboratory disciplines, including phlebotomy, clinical
      pulmonology and clinical microbiology. In phlebotomy, safety in blood collection
      is an ongoing issue and could be ensured by implementing staff education to
      reinforce methods of avoiding the risk of nerve injuries by selecting an
      appropriate vessel as well as the use of a butterfly needle. In the pulmonary
      function test, efforts are necessary to standardize the examination protocol, the
      quality control method, and prediction equation. In the microbiology laboratory,
      there is a transition of its role into activities for healthcare-associated
      infection control, such as the provision of an active surveillance culture,
      tabulated data on an antibiogram, and trends of antimicrobial-resistant bacteria
      in relation with antimicrobial use, as well as participation in an integrated
      team approach. All of the presentations in the symposium were educational and
      inspiring in providing information useful in daily laboratory practice. Combining
      the efforts in each discipline of the clinical laboratory on the basis of updated
      information would support the quality services of the laboratory.

PMID- 24450112
TI  - [The current problems and topics regarding pulmonary function tests].
AB  - Although the respiratory function test has a long history, the standardization of
      technical procedures and evaluation methods is still underway. Technologists have
      to be familiar not only with such standardized methods but also with quality
      control. Recently, a respiratory resistance test using the multi-frequency forced
      oscillation technique and exhaled nitric oxide measurement have been developed.
      As simple and non-invasive tests, these are useful for diagnosis and follow-up of
      patients with bronchial asthma or chronic obstructive lung diseases.

PMID- 24450113
TI  - [The pathophysiology of Alzheimer's disease with special reference to "amyloid
      cascade hypothesis"].
AB  - The neuropathological characteristics of the Alzheimer's disease (AD) brain
      include senile plaques, neurofibrillary tangles and neuronal cell loss
      extensively recognized in brain cortices. Biochemical studies revealed that
      senile plaques and neuronfibrillary tangles are composed mainly of amyloid beta
      protein and highly phosphorylated tau protein, a microtubule-associated protein,
      respectively. Abeta deposition in senile plaques was previously considered to
      initiate the pathological cascade of Alzheimer's disease (AD), suggesting that
      the aggregation of Abeta in insoluble Abeta fibrils plays an important role in
      its neurotoxicity ('amyloid cascade hypothesis'). However, the concentrations of
      Abeta required for fibrillization are higher than its physiological
      concentrations. In addition, cognitive decline in AD patients is not correlated
      with the levels of senile plaque formation. Currently, AD is believed to begin
      with synaptic dysfunction caused by soluble Abeta oligomers, playing a more
      important role in the etiology of AD than insoluble Abeta ibrils ('oligomer
      hypothesis').

PMID- 24450114
TI  - [Diagnosis, treatment and prevention of infectious diseases. Editorial: elderly
      society and clinical practice of pneumonia].

PMID- 24450115
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases: 1. Norovirus infection].

PMID- 24450116
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases; 2. High pathogenic avian
      influenza, including A (H7N9) infection].

PMID- 24450117
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases; 3. HIV infection].

PMID- 24450118
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases: 4. Macrolide-resistant
      Mycoplasma pneumoniae].

PMID- 24450119
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases; 5. Pertussis in adult].

PMID- 24450120
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases. 6. Multidrug resistant gram
      negative bacterial infections].

PMID- 24450121
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases; 7. Recent tick-borne
      disease--SFTS (severe fever with thorombocytopenia syndrome)].

PMID- 24450122
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: I.
      Countermeasures against epidemic infectious diseases. 8. Enterohemorrhagic
      Escherichia coli infection].

PMID- 24450123
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: II. Progress
      in diagnosis and treatments of infectious diseases; 1. Radiological diagnoses of
      pneumonias and mycobacterial diseases].

PMID- 24450124
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: II. Progress
      in diagnosis and treatments of infectious diseases; 2. A diagnosis of respiratory
      infections by a clone library analysis of the 16S ribosomal RNA gene].

PMID- 24450125
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: II. Progress
      in diagnosis and treatments of infectious diseases; 3. Concept of nursing and
      healthcare-associated pneumonia (NHCAP) and its management].

PMID- 24450126
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: II. Progress
      in diagnosis and treatments of infectious diseases: 4. Cutting edge of interferon
      gamma releasing assay (IGRA) for diagnosis of tuberculosis].

PMID- 24450127
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: II. Progress
      in diagnosis and treatments of infectious diseases: 5. Clinical usefulness of
      genotyping Mycobacterium avium].

PMID- 24450128
TI  - [Diagnosis treatment and prevention of infectious diseases: Topics: III. Various
      problems in antimicrobial agents; 1. Strategy and direction to overcome
      stagnation of antibiotic development].

PMID- 24450129
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: III. Various
      problems in antimicrobial agents; 2. Progresses and appropriate use of anti
      fungal agents].

PMID- 24450130
TI  - [Diagnosis, treatment and prevention of infectious diseases. Topics: III. Various
      problems in antimicrobial agents; 3. Advances in antituberculosis drugs].

PMID- 24450131
TI  - [Diagnosis treatment and prevention of infectious diseases. Topics: IV. Progress
      in understanding of VPD (vaccine preventable diseases); 1. Recognition and
      progress of vaccine preventable diseases in childhood].

PMID- 24450132
TI  - [Diagnosis treatment and prevention of infectious diseases. Topics: IV. Progress
      in understanding of VPD (vaccine preventable disease); 2. Recognition and
      progress of vaccine preventable diseases in adulthood].

PMID- 24450133
TI  - [Discussion meeting on the progress of diagnosis, treatment and prevention of an
      infectious diseases].

PMID- 24450134
TI  - [Case report; a case of anti-NMDA receptor encephalitis with a history of removal
      of ovarian teratoma].

PMID- 24450135
TI  - [Case report; a case of type 2 diabetes mellitus with frequent hypoglycemia due
      to insulin antibodies after switching insulin product].

PMID- 24450136
TI  - [Case report; a case of congenital haptoglobin deficiency diagnosed after
      transfusion for esophageal varix rupture].

PMID- 24450137
TI  - [The cutting-edge of medicine; association between the gut microbiota and
      intestinal disorders].

PMID- 24450138
TI  - [The cutting-edge of medicine; diagnosis and treatment of pneumonia in the
      elderly].

PMID- 24450139
TI  - [Report from the 17th Tokai Chapter Educational Seminar: tumor in internal
      medicine].

PMID- 24450140
TI  - [Series: clinical study from Japan and its reflections; incidence, clinical
      characteristics, long-term course, and comparison of progressive and non
      progressive cases of aphthous-type Crohn's disease: a single-center cohort
      study].

PMID- 24450141
TI  - [Series: diagnosis at a glance].

PMID- 24450142
TI  - [Epigenetic mechanism of major depression].
AB  - A recent genome-wide association mega analyses of major depression suggests that
      major depression is a polygenic and multifactorial disease and that a gene
      environmental interaction plays a pivotal role in its pathophysiology. Recent
      advances in epigenetics, such as improved methods for the measurement of DNA
      methylation, and covalent histone modifications, have shed light on the molecular
      mechanisms by which environmental stimuli affect gene expression in the brain and
      subsequently alter the cognitive function. Herein, we summarize how recent
      progress in epigenetics has advanced our understanding of the pathophysiology of
      major depression, particularly the role of glucocorticoid receptors and brain
      derived neurotrophic factor, including the development of stress vulnerability
      and resilience, and we discuss the possibility of using epigenetic drugs, such as
      histone deacetylase inhibitors, for the treatment of major depression.

PMID- 24450143
TI  - [Rate and characteristics of dementia patients who visit psychiatric emergency
      hospitals for the treatment of behavioral and psychological symptoms of dementia
      (BPSD) in Japan].
AB  - BACKGROUND: Neuropsychiatric symptoms and behavioral changes, known as behavioral
      and psychological symptoms of dementia (BPSD), are often observed in patients
      with dementia. BPSD impairs a patient's quality of life, increases the burden on
      the caregivers, and can be a predictor of the need for institutionalization. BPSD
      can aggravate on holidays or at night, when general psychiatric clinics are
      closed. When psychiatric symptoms aggravate on holidays or at night in patients
      with psychiatric disorders other than dementia, such as schizophrenia and manic
      psychosis, the patients visit psychiatric emergency hospitals. However, it has
      not been assessed whether patients with dementia visit psychiatric emergency
      hospitals for the treatment of BPSD on holidays or at night, although dementia
      patients are increasing and account for 10.5% of psychiatric outpatients in
      Japan. AIMS: To determine the percentage of dementia patients with BPSD in all
      psychiatric patients who visit psychiatric emergency hospitals, and the
      characteristics of patients with BPSD in Japan. METHOD: We developed two
      questionnaires. One was for psychiatric emergency hospitals and assessed the
      numbers of all patients, patients over 65 years old, and patients over 65 years
      and with BPSD or BPSD-like symptoms, who visited the psychiatric emergency
      hospitals on holidays or at night. The other questionnaire was for each patient
      over 65 years and with BPSD, and assessed the patients' characteristics,
      including their diagnosis, sex, what kinds of BPSD or BPSD-like symptoms brought
      them to the hospital, and whether they had visited a psychiatric clinic or
      hospital during the preceding 12 months. The questionnaires were sent to 360
      hospitals that belong to the Japan Psychiatric Hospitals Association and treat
      patients with acute psychotic symptoms or dementia. This prospective survey was
      conducted from October 1 to November 30, 2009. RESULTS: One hundred and forty
      three hospitals returned the questionnaires (response rate: 39.7%). In the survey
      period, 3,527 patients visited the psychiatric emergency hospitals on holidays or
      at night, but only 67 patients over 65 years old (1.9%) visited the hospitals for
      BPSD or BPSD-like symptoms. Thirty-four of the 67 patients were men, and their
      average age was 79.4 +/- 6.4 years old. Thirty-five patients had visited but 25
      patients had never visited psychiatric clinics or hospitals during the preceding
      12 months. Eight patients had physical complications that required examination
      for several days, while 57 patients did not require such treatment. Forty-seven
      patients were diagnosed with dementia. Patients with Alzheimer's disease (AD) (29
      patients) were the most common, followed by those with vascular dementia (VaD) (8
      patients) and those with dementia with Lewy bodies (DLB) (4 patients). Among the
      47 patients with dementia, agitation/aggression was the most frequent BPSD
      symptom (30 patients), followed by irritability (18 patients) and aberrant motor
      behaviors (17 patients). The BPSD symptoms observed at the psychiatric emergency
      hospitals differed due to the causative dementia. Agitation/aggression, aberrant
      motor behaviors, and irritability were the most frequent causative symptoms in
      AD, agitation/aggression and irritability were the most frequent causative
      symptoms in VaD, and hallucinations and illusions were the most frequent
      causative symptoms in DLB. CONCLUSIONS: Our survey revealed that few patients
      over 65 years old visited psychiatric emergency hospitals for BPSD on holidays or
      at night in Japan, and that many of them had not regularly visit psychiatric
      clinics or dementia hospitals in the preceding 12 months. These results indicate
      that dementia patients need to visit their doctors regularly to avoid visiting
      psychiatric emergency hospitals on holidays or at night, and caregivers should be
      aware that they can visit psychiatric emergency hospitals for the treatment of
      BPSD on holidays or at night.

PMID- 24450144
TI  - [Alzheimer's disease and depression].
AB  - In Alzheimer's disease (AD) patients, depression is not rare. The prevalence of
      major depressive episodes has been reported to be within the range of 20-25% in
      AD patients, despite there being no association between the severity of AD and
      prevalence of comorbid depressive symptoms or diagnosed depression. Depression in
      AD patients is associated with greater impairment of the quality of life and an
      increased caregiver burden. As well as earlier placement in a nursing home, bio
      psycho-social factors are also associated with the manifestation of depression in
      AD patients, and biological factors, such as the brain pathology, may be the main
      influence. Depressive mood, loss of interest, and anxiety are among the most
      marked symptoms of depression in AD patients. In comparison with major depressive
      disorder, in depression in AD, psychomotor retardation is more prominent, while,
      in major depressive disorder, somatic anxiety is more marked. In the treatment of
      depression in AD, non-pharmacological and pharmacological therapies are applied.
      Basically, support and encouragement are required. In addition, psychosocial
      interventions, such as validation, reminiscence, physical exercise, and
      interventions for caregivers of those with dementia have been reported to be
      useful. The results of RCT with antidepressants are inconsistent. As the efficacy
      of cholinesterase inhibitor for depression in AD has been reported, it is
      reasonable to initially provide treatment with cholinesterase inhibitors rather
      than antidepressant therapy.

PMID- 24450145
TI  - [Depression in dementia with Lewy bodies].
AB  - Depression is a risk factor for dementia in general, including Alzheimer's
      disease (AD), its premorbid signs are commonly observed, and the morbidity of
      depression is higher in dementia patients. Dementia with Lewy bodies (DLB) is
      considered to have an even higher depression prevalence and premorbid depression
      rate than other dementias such as AD. This led to depression being listed as a
      supportive feature in the 2005 criteria for the clinical diagnosis of DLB.
      However, studies investigating the difference in depression between AD and DLB
      failed to show consistent results. We examined the Geriatric Depression Scale
      score, which is designed specifically to rate depression in the elderly, for DLB
      and AD patients. The scores for DLB patients were twice as high as those for AD
      patients. There was no correlation between the GDS score and age, sex, or Mini
      Mental Sate Examination scores. Depression-specific symptoms were more frequent
      in the DLB group than non-specific symptoms, while less than one third of DLB
      patients with very high GDS scores were diagnosed with depression or prescribed
      antidepressants for depressive symptoms. Other researchers reported that
      depression of DLB was associated with a higher prevalence of psychiatric symptoms
      other than major depression, and suggested that depression of DLB might be a part
      of psychiatric syndrome. There has been no systematic study on the validity or
      risk of pharmacological therapy, as well as the necessity of intervention, for
      depression or a high GDS score in DLB. Therefore, intervention must rely on the
      clinical decision of each doctor. In spite of the paucity of current findings,
      studies on depression of DLB may play a key role in the elucidation of its
      neuropathology and psychopathology and offer a new view point on understanding
      depression itself.

PMID- 24450146
TI  - [Depression in Parkinson's disease].
AB  - Depression affects Parkinson's disease (PD) patient's QOL. Although it changes
      with the diagnostic criteria used, the frequency of depression in PD is
      approximately 10-30%. Anhedonia is characteristic in PD. According to research on
      anhedonia in PD using the Snaith-Hamilton Pleasure Scale (SHAPS), the positive
      ratio of anhedonia is high in PD. The SHAPS score significantly correlates with
      the severity of PD and duration of the disease. An examination of the literature
      on depression before the development of motor symptoms of PD revealed that the
      risk of PD is high in patients with a history of depression. Pathologically, the
      substantia nigra is affected in the later stages and raphe nuclei are affected in
      the early stages. This suggests that depression is a prodromal symptom of PD.

PMID- 24450147
TI  - [Cognitive impairment in Parkinson's disease].
AB  - Cognitive impairment is a common finding in Parkinson's disease (PD), even in the
      early stages. The concept of mild cognitive impairment (MCI) in PD was recently
      formalized with diagnosis being reached after impairments in neuropsychological
      tasks become significant in at least one domain. The brain profile of cognitive
      deficits involves executive functions (e. g., planning, set shifting, set
      maintenance, problem solving), attention and memory function. Memory deficits are
      characterized by impairments in delayed recall, temporal ordering and conditional
      associate learning. PD patients demonstrate relatively preserved recognition.
      Visuospatial dysfunctions have also been reported, while language is largely
      preserved. The existence of two distinct mild cognitive syndromes has also been
      suggested. One of these affects mainly the frontostriatal executive deficits that
      are modulated by dopaminergic medications and by a genetically determined level
      of prefrontal cortex dopamine release. The other affects the more-posterior
      cortical abilities, such as visuospatial and memory functions, and is suggested
      to be associated with an increased risk for conversion to dementia. Cross
      sectional studies have commonly reported dementia in 20-30% of PD patients,
      although the 8-year cumulative incidence of dementia may be as high as 78%.
      Factors associated with dementia in PD are age at onset, age at the time of
      examination, akinetic-rigid form PD, depression, hallucination, rapid eye
      movement sleep behavioral disorder and severe olfactory deficits. Clinical
      features generally involve the same type of deficits as those found in MCI
      patients, which are more severe and more extensive. The phenomenology of the
      dementia syndrome is similar to that seen in dementia with Lewy bodies, and
      clinicopathological correlation studies have revealed varying results with regard
      to neurochemical deficits and the pathological substrate underlying cognitive
      impairment and dementia. Early cognitive impairment, particularly in the form of
      executive dysfunction, is indicative of mainly fronto-striatal pathologic changes
      and might originate during nigrostriatal and subsequent mesocortical dopamine
      denervation. A potential parallel noradrenergic deficit and cholinergic deficit
      disturbance in patients without dementia might also contribute to MCI. Extensive
      pathological changes in Lewy bodies lead to widespread cortical and subcortical
      degeneration and profound cholinergic deficits, and might lead to the development
      of dementia. Several studies have revealed a significant correlation between
      dementia and Alzheimer-type pathology.

PMID- 24450148
TI  - [The diagnosis and treatment of delirium].
AB  - Delirium is a common condition, and is associated with adverse outcomes,
      including increased morbidity, increased mortality, and increased health services
      utilization. However, no medications against delirium have yet been approved.
      Thus, delirium is still unexplored not only in the psychiatric field, but also in
      all medical services. In the review, delirium etiologies, prediction, diagnosis,
      prevention, and treatment are outlined. Especially, future strategies of
      prediction and prevention, and the evaluation of antipsychotics from a safety
      perspective, are presented. On the basis of such points, a treatment algorithm is
      proposed.

PMID- 24450149
TI  - [Involvement of cyclin-dependent kinase CDK1/CDC28 in regulation of cell cycle].
AB  - Cyclin-dependent kinases (CDKs) are a family of enzymes essential for the
      progression of the cells through the cell cycle in eukaryotes. Moreover, genetic
      stability-maintaining processes, such as checkpoint control and DNA repair,
      require the phosphorylation of a wide variety of target substrates by CDK. In
      budding yeast Saccharomyces cerevisiae, the key role in the cell cycle
      progression is played by CDK1/CDC28 kinase. This enzyme is the most thoroughly
      investigated. In this review the involvement of CDC28 kinase in regulation of the
      cell cycle is discussed in the light of newly obtained data.

PMID- 24450150
TI  - [Differential expression of genes that encode glycolysis enzymes in kidney and
      lung cancer in humans].
AB  - Glycolysis is a main catabolic pathway of glucose metabolism, accompanied by ATP
      synthesis. More than 30 enzymes are involved in glycolysis, and genes that encode
      them can be considered housekeeping genes due to the high conservatism and
      evolutionary antiquity of the process. We studied the expression of these genes
      in kidney papillary cancer and planocellular lung cancer via the bioinformatic
      analysis of transcriptome database and method of quantitative real time PCR.
      Quantitative analysis of mRNA level demonstrated that only a part ofgenes that
      encode glycolysis enzymes maintain relatively stable mRNA level, including the
      HK1, ADPGK, GPI, PGK1, and PKM2 genes in kidney papillary cancer and the ADPGK,
      ALDOA, GAPDH, PGK1, BPGM, ENO1, and PKM2 genes in planocellular lung cancer. The
      frequent increase in the mRNA expression of PFKP, ALDOA, and GAPDH genes in
      kidney cancer, as well as the GPI gene in lung cancer, were detected for the
      first time by real time PCR. For other genes, their differential expression was
      demonstrated; the cases of both a decrease and increase in the mRNA level were
      detected. Thus, several genes that can be used as control genes in transcriptome
      analysis by real time PCR in kidney and lung cancer, as well as a number of
      differentially expressed genes that can be potential oncomarkers, were
      identified.

PMID- 24450151
TI  - [Polymorphism and structural variation of rps16 group-II intron in the Solanum
      species].
AB  - Nucleotide sequences of the self-splicing group-II intron of rps16 have first
      been determined in nine species of the Solanum genus. It was found that the
      observed variations in the intron length (855-864 bp) was associated with indels
      of 1 to 9 b. Altogether, five indels and 50 nucleotide substitutions were
      detected, which were used to identify six Solanum haplotypes. Although the intron
      sequence was in general fairly well conserved, the distribution of the described
      mutations among its structural elements corresponding to six preRNA domains was
      qualitatively and quantitatively nonuniform. The highest polymorphism levels were
      observed in domains I, II, and IV. The sequence of domain V was absolutely
      invariable, which is in agreement with its functional significance.

PMID- 24450152
TI  - [Peculiarities of phosphoglycerate kinase-1 pseudogene evolution in Schrenck
      salamander (Salamandrella schrenckii Strauch, 1870)].
AB  - Processed copies of genes generally evolve in neutral mode as pseudogenes,
      however, some of them might be important sources of new functional genes. The
      psiPGK1 pseudogene has been discovered in Schrenck salamander (Salamandrella
      schrenckii, Amphibia, Caudata, Hynobiidae) via polymerase chain reaction used to
      amplify the phosphoglycerate kinase 1 gene (PGK1). This pseudogene is an
      intronless copy of PGK1 gene absent of exon 6. Analysis of psiPGK1 pseudogene
      polymorphism has demonstrated that it lacks mutations, which results in shifts in
      the stop codons and reading frames, as well as that the interspecies variation of
      this pseudogene was inconsistent with the neutral model of evolution. In
      addition, the pattern of phylogeographic differentiation of the psiPGK1 variants
      mainly coincides with that observed in mitochondrial DNA. These observations
      allow it to be suggested that the psiPGK1 pseudogene is a new functional gene in
      the Schrenck salamander.

PMID- 24450153
TI  - Development of a microsatellite set for paternity assignment of captive rhesus
      macaques (Macaca mulatta) from Anhui province, China.
AB  - Microsatellites are playing an important role in paternity assignment of animals.
      Given the cost and effort, it would be optimal to develop a minimal
      microsatellite marker set for paternity testing. This study was the first to
      assess paternity in a captive colony of rhesus macaques (Macaca mulatta) from the
      Chinese province of Anhui using 10 polymorphic microsatellites. Results indicated
      that if at least 6 loci were genotyped, the probability of paternity assignment
      success was nearly 100%. Our results provide a panel of 6 markers that is
      effective for assessing paternity of subspecies M. m. siamica of Anhui origin.

PMID- 24450154
TI  - Genetic characterization of Colombian Bahman cattle using microsatellites
      markers.
AB  - Genetic structure and diversity of 3789 animals of the Brahman breed from 23
      Colombian regions were assessed. Considering the Brahman Zebu cattle as a single
      population, the multilocus test based on the HW equilibrium, shows significant
      differences (P < 0.001). Genetic characterization made on the cattle population
      allowed to examine the genetic variability, calculating a H(o) = 0.6621. Brahman
      population in Colombia was a small subdivision within populations (F(it) =
      0.045), a geographic subdivision almost non-existent or low differentiation
      (F(st) = 0.003) and the F(is) calculated (0.042) indicates no detriment to the
      variability in the population, despite the narrow mating takes place or there is
      a force that causes the variability is sustained without inbreeding actually
      affect the cattle population. The outcomes of multivariate analyses, Bayesian
      inferences and interindividual genetic distances suggested that there is no
      genetic sub-structure in the population, because of the high rate of animal
      migration among regions.

PMID- 24450155
TI  - [Association of a single nucleotide substitution in intergenic region of
      chromosome 4 with traits of egg quality in domestic chickens].
AB  - The association of SNP2-1 with egg quality traits in domestic chickens was
      analyzed. SNP2-1 alleles were significantly associated with the thickness of
      eggshells in chickens of the UK-72 line. The substitution of the SNP2-1 allele
      Tfor the C allele had an effect of 35 +/- 15 microm, which corresponds to one
      standard deviation. For this trait, the effect of the Tallele was dominant. SNP2
      1 was also associated with other traits, including shell weight, egg-laying
      capacity in 60-week-old chickens (line UK-72), and egg weight in 60-week-old
      chickens (line cross CD). Thus, the QTL marked with SNP2-1 has a pleiotropic
      effect that depends on the chicken strain. Candidate genes located on chromosome
      4 in close vicinity of SNP2-1 are discussed.

PMID- 24450156
TI  - [Mitochondrial DNA polymorphism in populations of aboriginal residents of the Far
      East].
AB  - An analysis of mtDNA polymorphism in eight populations of aboriginal residents (N
      = 519) of the Far East has been performed. The majority of haplogroups revealed
      in the examined groups were of East Eurasian origin. Haplogroup D was revealed in
      seven populations and its frequency varied from 2.8% in Koryaks to 28.3 and 28.9%
      in Nanaians and Evenks, respectively. Chukchi and Koryak populations, which
      belong to the same language family, exhibited haplogroup G, which has the same
      motive and indicates the genetic kinship of both populations. The presence of
      East Eurasian haplogroups A and D with a strong predominance of haplogroup A in
      Chukchi indicates the closer relationship of this population both with Asian and
      Canadian Eskimos and northern Atapasks on the other side of Bering Strait. The
      high level of genetic variability was revealed in populations belonging to the
      Tungus-Manjur group. The high frequency of east Eurasian haplogroups in Nanaians
      could result from close historical associations with Siberian Evenks.

PMID- 24450157
TI  - [Mutagen influence with different mechanisms of action on DNA global methylation
      in human whole-blood lymphocytes in vitro].
AB  - Data that support the evidence of mutagens known to cause epigenetic
      abnormalities that could potentially result in genomic instability and the
      development of cancer rather than to modifications in the human genome at the
      gene and chromosomal levels only. The level of global methylation in human
      lymphocytes in vitro caused by exposure to two mutagens with different mechanisms
      of action, i.e., dioxidine and methyl methanesulphonate (MMS), was demonstrated
      in the present study. Global methylation was assessed by methyl-sensitive comet
      assay. An increase in the level of global methylation to 45.64% was revealed
      during culturing with dioxidine in a concentration of 0.01 mg/mL (p < 0.001),
      while the addition of dioxidine in a concentration of 0.1 mg/mL resulted in a
      decreased level of methylation up to 42.31% (p < 0.001). The addition of M MS in
      concentrations of 0.0025 and 0.01 mg/mL resulted in minor but significant
      modifications (p < 0.05) of the global methylation level ranged within natural
      variations in global methylation. Accordingly, the addition ofdioxidine in the
      concentration of 0.1 mg/mL might cause genomic instability and might be
      considered a potential carcinogen.

PMID- 24450158
TI  - [MFN2 gene analysis in patients with hereditary motor and sensory neuropathy from
      Bashkortostan Republic].
AB  - Hereditary motor and sensory neuropathy (HMSN) type IIA is caused by mutations in
      the mitofusin type-2 (MFN2) gene and represents one of the most common axonal
      forms of HMSN. We determined the spectrum and frequency of MFN2 gene mutations in
      patients from the Bashkortostan Republic (BR). Four different mutations were
      revealed in 5 out of 170 unrelated patients, i.e., c.2113G>A (p.Val705Ile) (1.2%
      among all types of H MSN in the total sample of patients and 2% among patients of
      Tatar ethnicity). This mutation was described previously; c.775C>T (p.Arg259Cys)
      (0.6%, in the total sample of patients and 2% among the patients of Tatar
      ethnicity); c.776G>A (p.Arg259His) (0.6% in the total sample of patients and 1.5%
      among the patients of Russians ethnicity); and c.2171T>C (p.Leu724Pro) (1.2% in
      the total sample of patients and 7.4% among the patients of Bashkirs ethnicity).
      These are new mutations that were not observed among healthy family members and
      in control samples of healthy subjects. Five identified nucleotide substitutions
      represent single nucleotide polymorphisms of the gene, including c.892G>A
      (p.Gly298Arg), c.957C>T (Gly319Gly), and c1039-222t>c, which were described
      previously, while c.175+28c>t and c.2204+15t>c represent new nucleotide
      substitutions in the intron regions of the gene.

PMID- 24450159
TI  - [Ubiquitous downregulation of InR gene expression affects stress associated
      hormone metabolism in Drosophila females].
AB  - The effect of the ubiquitous downregulation of insulin receptor (InR) gene
      expression on the metabolism of juvenile hormone (JH) and dopamine (DA) in young
      females of D. melanogaster under normal conditions and heat stress is studied.
      The activity ofJH degradation and alkaline phosphatase (ALP, an enzyme regulating
      DA synthesis) were used as indicators of JH and DA levels, respectively. We
      demonstrated that, under normal conditions, the ubiquitous inhibition of the InR
      gene expression in D. melanogaster females induced an increase in the JH
      degradation and ALP activity. As we have already shown, this is indicative of the
      decrease in the concentration of the above hormones. It was also found that the
      total inactivation of InR does not affect the initiation ofJ H and DA metabolic
      system response to heat stress; however, it does affect its intensity. Thus, the
      involvement of the insulin signaling pathway in the regulation of the JH and DA
      metabolism in Drosophila females was demonstrated in vivo under normal and stress
      conditions.

PMID- 24450160
TI  - [Novel miRNA genes methylated in lung tumors].
AB  - MicroRNAs play an important role in the regulation of expression of many genes
      and are involved in carcinogenesis. The regulation of miRNA gene expression can
      involve the methylation of promoter CpG islands. In this work, the methylation of
      six miRNA genes (mir-107, mir-125b-1, mir-130b, mir-137, mir-375, and mir-1258)
      in non-small-cell lung cancer (NSCLC) was studied for the first time by
      methylation-specific PCR using a representative set of specimens (39 cases). Four
      new genes (mir-125b-1, mir-137, mir-375, and mir-1258) methylated in primary
      NSCLC tumors were identified with frequencies of 56, 31, 56, and 36%,
      respectively. The frequencies of miRNA promoter methylation in DNA of tumors and
      histologically normal tissues differed significantly (P < or = 0.05 by Fisher's
      test). In lung tissues of 20 donors without a history of cancer, these genes were
      only methylated in a few cases. It was also shown that the previously unstudied
      promoter CpG islands of mir-107 and mir-130b were not methylated in NSCLC. The
      frequencies of mir-125b-1 and mir-137 methylation were shown for the first time
      to correlate with NSCLC progression (clinical stage and metastasis).

PMID- 24450161
TI  - [Compartmentalization of neral non-synaptic plasticity at subcellular level].
AB  - One of the most efficient ways of CNS response to the variety of external and
      internal stimuli is a selective increase of excitability of neurons, acquired,
      for instance, during learning process. It is now well established, that
      persistent non-synaptic plasticity that emerging after learning, as well as
      synaptic one may serve an a substrate for long-term memory. Though, it remains
      unknown how the non-synaptic plasticity contributes to the alteration of the
      states of neuronal networks, which the long-term memory depends directly on. The
      explanation of how the non-synaptic plasticity is translated into the modified
      states of the neuronal networks and modified behavior remains one of the most
      important challenges of the contemporary research in the field of learning and
      memory. Also, little is known about the specific neuronal compartments ofthe axon
      and dendretic tree of that subjected to plastic changes in the context of
      morphological features of individual neuron and the efficiency of its input and
      output synapses subjected to indirect modifications due to non-synaptic
      plasticity and the influence of non-synaptic plasticity on the efficiency of
      neuronal synapses.

PMID- 24450162
TI  - [Neurochemical mechanisms of depression-like behavior in WAG/Rij rats].
AB  - Behavior in the light-dark choice, open-field, sucrose consumption/preference and
      forced swimming tests, monoamines and their metabolites level in 6 brain
      structures (prefrontal cortex, nucleus accumbens, striatum, hypothalamus,
      hippocampus, amygdala), and density of D2-like dopamine receptors in 21 brain
      regions were studied in WAG/Rij and Wistar rats. WAG/Rij rats exhibited symptoms
      of depression-like behavior such as increased immobility in the forced swim test
      and decreased sucrose consumption/preference (anhedonia). Substantial changes in
      behavior indicating increased anxiety in WAG/Rij rats were not revealed.
      Neurochemical abnormalities suggesting hypofunction of the mesolimbic
      dopaminergic brain system were found in "depressive" WAG/Rij rats compared with
      "normal" Wistar rats: decreased levels of noradrenaline, dopamine, 3,4
      dihydroxyphenylacetic acid, 3-methoxytyramine in the nucleus accumbens, and
      increased density of D2-like dopamine receptors in the nucleus accumbens and
      ventral tegmental area. Reduced levels of dopamine were also observed in the
      prefrontal cortex and striatum. No substantial changes in the content of
      monoamines and their metabolites have been revealed in the hypothalamus,
      hippocampus and amygdala as well as in the content ofserotonin and its metabolite
      5-hydroxyindolacetic acid in all studied brain structures with the exception of
      increased level ofserotonin in the amygdala. Results suggest that hypofunction of
      the mesolimbic dopaminergic brain system (nucleus accumbens) is a neurochemical
      mechanism of depression-like behavior in WAG/Rij rats.

PMID- 24450163
TI  - [Structural and functional peculiarity of brain activity to performance and
      imaginary motor tasks in healthy persons (EEG and fMRI study)].
AB  - Bioelectrical (EEG) and hemodynamic (fMRI-response) cerebral reactions to
      performance and imaginary motor tasks by right or left hand were analyzed in 15
      right-handed healthy persons (21-39 years old). During actual movement the main
      fMRI-response was registered in the area of central gyrus of the hemisphere
      contralateral to the working hand. Areas of activation were also revealed in the
      supplemental motor area and the ipsilateral hemisphere of the cerebellum. EEG
      data showed coherence increase in high frequency alpha- and beta-bands in the
      activated hemisphere. In imaginary motor tasks the intensity and topography of
      fMRI-response became the more variable; response was decreased in the motor area
      and in cerebellum, they increased in the subcortical structures and in the
      parietal association zones. EEG changes were very variable in this situation
      also; it was observe an increase of EEG coherence in the right hemisphere for
      higher frequency of alpha and beta spectral bands. Changes of power spectrum
      parameters were similar to performance and imaginary motor tasks. Spectrum power
      and middle frequency of beta band were increased. Topographically these changes
      did not correspond to activated hemisphere and it was more in the left
      hemisphere. These changes were reflected nonspecific component of reaction.

PMID- 24450164
TI  - [FMRI-study of speech perception impairment in post-stroke patients with sensory
      aphasia].
AB  - The aim of the study was to find neurophysiological correlates of the primary
      stage impairment of speech perception, namely phonemic discrimination, in
      patients with sensory aphasia after acute ischemic stroke in the left hemisphere
      by noninvasive method of fMRI. For this purpose we registered the fMRI-equivalent
      of mismatch negativity (MMN) in response to the speech phonemes--syllables "ba"
      and "pa" in odd-ball paradigm in 20 healthy subjects and 23 patients with post
      stroke sensory aphasia. In healthy subjects active brain areas depending from the
      MMN contrast were observed in the superior temporal and inferior frontal gyri in
      the right and left hemispheres. In the group of patients there was a significant
      activation of the auditory cortex in the right hemisphere only, and this
      activation was less in a volume and intensity than in healthy subjects and
      correlated to the degree of preservation of speech. Thus, the method of recording
      fMRI equivalent of MMN is sensitive to study the speech perception impairment.

PMID- 24450166
TI  - [The efficiency of recognition of the size of segments of line by the observers
      with different parameters of the cognitive style].
AB  - We estimated efficiency of recognition of the size of segments of line by the
      persons with different parameters of cognitive style: the field dependence--field
      independence, the analytically--synthetically style, the flexible--rigid
      cognitive control. The size of segments of line was judged in task of the
      magnitude of the Ponzo illusion measurements. It was established, that the
      magnitude of the Ponzo illusion significantly less in subjects with the field
      independence cognitive style, than with field independence. The persons with the
      flexible type of the cognitive control showed the tendency to more accurate
      perception of the size of the segments in the Ponzo figure, than with the rigid
      cognitive control. The rinteraction between the analytically--synthetically style
      of the categorization and the magnitude of the Ponzo illusion is not fixed.

PMID- 24450165
TI  - [Saccade latency and pattern of saccade response in the experimental scheme
      "double step"].
AB  - To investigate the decision-making process at the saccade programming we used
      modification of the "double step" experimental scheme, in which two short stimuli
      are presented successively in the opposite semifields (puls overshoot--scheme).
      The dependence of saccades to visual stimuli number, responses pattern (two
      saccades, or a single saccade to the second stimulus) and the value of saccade
      latency from the first stimulus duration (150 or 50 ms), the spatial stimuli
      arrangement and the individual characteristics of the subjects was shown. The
      findings suggest the relationship of attention and decision making processes at
      saccade programming and indicate to the possible influence of prognostic
      processes on the saccadic response "pattern" at the expectation period in the
      experimental "double step" scheme.

PMID- 24450167
TI  - [Effects of the delta-sleep inducing peptide on neuronal activity in the dorsal
      hippocampus of rats with different behavior in the open field after stimulation
      of the positive and negative emotionalistic structures of the brain].
AB  - We studied the cerebral mechanisms of positive and negative emotions in rats with
      different behavior in open field, reflecting stress resistance and neuronal
      effects of delta-sleep-inducing peptide (DSIP). In 20 male Wistar rats 107
      neurons of dorsal hippocampus (57 neurons in active in open field--prognostically
      resistant to emotional stress and 50 inpassive--prognostically predisposed rats)
      were registered after positive (lateral hypothalamus--LH) and negative
      (ventromedial hypothalamus--VMH) emotional centers electric stimulation.
      Hippocampal neurons in active rats were less sensitive to stimulation of LH and
      VMH compared with passive ones. DSIP microiontophoretic application before LH
      stimulation decreases neuronal responses in both active and passive animals. DSIP
      increases dorsal hippocampus neurons sensitivity to VMH stimulation in active
      rats and decreases in passive ones.

PMID- 24450168
TI  - [Transcriptome alteration in hippocampus under the treatment of tuftsin analog
      Selank].
AB  - The effect of single and course administration of Selank (Thr-Lys-Pro-Arg-Pro-Gly
      Pro) in the dose 200 microg/kg on the rat hippocampus transcriptional profile
      were studied using cDNA microarray technology. It was shown that mRNA levels of
      36 genes changed more than 2-fold after a single intranasal Selank
      administration, and 20 genes--after course administration. It should be noted
      that most of them encode proteins associated with the plasma membrane (including
      transmembrane proteins). This suggests that Selank is able to regulate ion
      homeostasis of hippocampal cells and thereby modulate different ion-dependent
      processes, which include the processes of learning and memory formation.

PMID- 24450169
TI  - [The analysis of maternal behavior in tame and aggressive rats].
AB  - Maternal behavior in rodents is associated with long-term programming of
      individual coping capacities in the offspring and includes a large number of
      components. This work was aimed to study maternal behavior in tame and aggressive
      gray rats selected for absence and enhancement of aggressiveness towards human.
      The study was carried out from 1 to 12 days of nursing at various time of day. It
      was shown that the frequency of "outside the nest" and passive nursing was higher
      and the frequency of maternal arched-back nursing and mother licking/grooming was
      lower in tame compared to aggressive dams especially at the first week of
      nursing. The tame dams spent less time building nest, they displayed "rest" and
      self-grooming more frequently. Beginning from the first week of nursing the
      frequency of "outside the nest" increased in the morning (09:00) and the evening
      and night (18:00 and 22:00) in tame dams, while the increase of activity was
      observed in aggressive females only in dark phase (22:00). In the third week of
      nursing the similar circadian changes of activity were observed in tame and
      aggressive dams. It is supposed that decreased anxiety in tame compared to
      aggressive dams could provoke the attenuation of maternal behavior.

PMID- 24450170
TI  - [Neurotensin influence on painful stress afteractions in rats with neurotoxic
      damages of serotoninergic structures of brain substantia nigra].
AB  - The purpose of the research was to reveal the features of neurotensin influence
      on behavior of rats with damages of 5-HT structures of substantia nigra. Changes
      of recall of passive avoidance conditioned reactions, and also painful
      stimulation aftereffects on locomotor activity of rats in "open field" were
      studied. It was shown that neurotoxin 5,7-DOT administration into substantia
      nigra impaired recall of passive avoidance reactions and as well weakened
      oppressive aftereffects of painful stimulation. Administration of serotonin 5
      HT1A receptors antagonist p-MPPF insert similar influence on aftereffects of
      painful stimulation. Neurotensin microinjections into caudate nucleus just before
      painful stimulation prevented disturbances of defensive behavior and its
      aftereffects evoked by neurotoxin. Neurotensin administration into substantia
      nigra in 24 h after painful stimulation didn't exert any significant influence on
      passive avoidance reactions but increased motor activity against a background of
      its recall. Effects of neurotoxin administrations into substantia nigra connected
      with weakened of painful stress influence on motor activity in rats. The
      prevention of this effect development after neurotensin administrations into
      caudate nucleus may be specified by recovery of recall passive avoidance
      reactions destroyed by neurotoxin action and is explained by normalization of
      relationships balance of 5-HT and dopaminergic brain systems.

PMID- 24450171
TI  - [Effect of prenatal stress and 17beta-estradiol on anxiety and depressive
      behaviors of ovariectomized female rats].
AB  - The present study evaluated the ability of 17beta-estradiol to induce anxiolytic-
      and antidepressant-like action in adult ovariectomized female offspring of dams
      that were restrained under lights for 1 h on gestational days 15-19. There were
      no differences in behavioral profile of ovariectomized prenatal stressed and
      control female rats. Injections of 17beta-estradiol (0.5 microg/rat) in the
      course of two week had minimal behavioral effects in control rats, but produced a
      decrease of immobility in the forced swimming test and anxiety level in the
      elevated plus maze in prenatal stressed rats. These findings suggest that
      ovariectomized prenatal stressed female rats demonstrate more sensitivity to
      estrogen-replacement.

PMID- 24450172
TI  - [Evaluation of a long-term sensomotor deficit after neonatal rat brain
      ischemia/hypoxia].
AB  - The application of magnetic resonance imaging method showed that ischemia/hypoxia
      of the brain of neonatal rats made by the protocol suggested by Levine-Rice
      induces one-sided lesions in the areas of cerebral cortex, striatum and
      hippocampus. Unilateral ischemic injury leads to a long-term sensorimotor and
      behavioral distortions within 90-115 days after the operation which has been
      tested in animals by the battery of tests including Cylinder, Beam-walking,
      Staircase and Limb-placing test. Chosen battery of tests in combination with
      magnetic resonance imaging allows to reliably estimate the long-term sensorimotor
      recovery in adult animals suffered an injury in neonatal age.

PMID- 24450173
TI  - [Individual variation in the development of the common toad, Bufo bufo (Anura,
      Bufonidae): I. Timing of development and anomalies of external structure].
AB  - Parameters of development have been analyzed in all offspring (1633 ind.) from
      the same spawn of one pair of common toads under conditions of laboratory
      rearing, with natural elimination being reduced to a minimum. The results show
      that the range of developmental options for the species is much wider than it
      follows from the standard tables of development. "Background anomalies"
      (Kovalenko, 2003) in the external structure of developing larvae are described
      and their probable frequencies under nearly optimal conditions are indicated.

PMID- 24450174
TI  - [Individual variation in the development of the common toad, Bufo bufo (Anura,
      Bufonidae): 2. Diagnostic characters of the axial skeleton].
AB  - Analysis of individual variation in diagnostic characters of the axial skeleton
      has been performed in all offspring (1633 ind.) from the same spawn of one pair
      of common toads under conditions of laboratory rearing, with natural elimination
      being reduced to a minimum. More than 50 skeletal anomalies have been recorded.
      Factual data are presented that characterize deviations from the species norm in
      the frequency of "background anomalies" (Kovalenko, 2003). Correlations between
      manifestations of different variants of character states are considered. The
      problem of norm and anomaly in individual variation is discussed.

PMID- 24450175
TI  - [Individual variation in the development of the common toad, Bufo bufo (Anura,
      Bufonidae): 3. Limitations of individual variation and their causes].
AB  - The results of studies on the axial skeleton of the common toad (a model species)
      have been used to analyze factual limitations of individual variations. The
      results show that the states of the studied characters do not freely combine with
      each other but are subject to certain morphogenetic limitations. The causes of
      most these limitations have been revealed during the study. Classification of the
      main factors limiting individual variation in the course of development is
      presented.

PMID- 24450176
TI  - [Initial stages of the root system development in three Impatiens species
      (Balsaminaceae family)].
AB  - Peculiarities of the development of morphological and anatomical structures of
      the root system have been studied in the seedlings of three Impatiens species at
      the early and subsequent stages of their ontogenesis. Correspondence between the
      revealed structure and the ecological originality of species, especially in the
      case of the aboriginal touch-me-not balsam, whose allorhizy can be revealed only
      at the anatomical level, is discussed.

PMID- 24450177
TI  - [Role of hydration in ovulation of common frog oocytes in vitro].
AB  - Stimulation of ovulation of the common frog Rana temporaria oocytes with
      homologous pituitary extract caused an increase in their volume. Factors that are
      known to inhibit hydration in teleostean oocytes (potassium-free Ringer solution
      and inhibitor of Na+, K(+)-ATPase--ouabain), as well as use of aquaporin
      inhibitors (mercuric chloride and methylmethanethiosulphonate) inhibited also
      homologous pituitary extract-induced volume increase in follicle-enclosed oocytes
      and let to reduced percentage of ovulated oocytes. Volume of denuded oocytes
      remained unchanged in the course of maturation when exposed to progesterone or
      other treatments. The data obtained suggest that stimulation ofoocyte ovulation
      in the common frog caused an increase in their hydration that in necessary for
      their ovulation but this did not occur in denuded cells.

PMID- 24450178
TI  - [Taxonomical status of the psychrotolerant Antarctic microorganisms].
AB  - The aerobic chemoorganotrophic bacteria, dominating in soils and phytocenosis of
      the Antarctic Region, on combination of morphological and biochemical properties
      belong to several taxons of Bacteria domain. Gram-negative strains 3189, 3415
      (fam. Halomonadaceae, Halomonas sp.) and 3088, 3468, 3469 (fam. Moraxellaceae,
      Psychrobacter sp.) belong to phylum Proteobacteria, to class Gammaproteobacteria.
      Gram-negative strains 3294 3392 (Rhizobiales, fam. Methylobacteriaceae,
      Methylobacterium sp.) relate to class Alphaproteobacteria of this phylum. Gram
      positive strains 3179, 3275, 3470, 3471 (fam. Microbacteriaceae, Cryobacterium
      sp.), 3054, 3058, 3411 (fam. Corynebacteriaceae, Corynebacterium sp.) and 3194,
      3398 (fam. Micrococcaceae, Micrococcus sp.) relate to phylum Actinobacteria,
      class Actinobacteria. Thus, the psychrophilic and psychrotolerant Antarctic
      bacteria (aerobic chemoorganotrophic) isolated from phytocenosis and soils of
      polar region are characterized by wide taxonomic variety.

PMID- 24450179
TI  - Isolation of Streptomyces globisporus and Blakeslea trispora mutants with
      increased carotenoid content.
AB  - Hyperpigmented mutants of Streptomyces globisporus 1912-Hp7 and Blakeslea
      trispora 18(+), 184(-) were isolated by action of hydrogen peroxide and
      nitrosoguanidine, correspondingly, from initial strains S. globisporus 1912-4Lcp
      and B. trispora 72(-), 198(+). The carotenoids of dry biomass of obtained
      strains, rubbed thoroughly with glass powder by a pestle in porcelain mortar were
      extracted by acetone and purified by TLC. Identification of the individual
      carotenoids was performed by means of HPLC and LC/MS spectrometry. It was shown
      that strain S. globisporus 1912-4Crt produced beta-carotene/lycopene (6.91/3.24
      mg/L), mutants 1912-4Lcp and 1912-7Hp synthesized only lycopene (26.05 and 50.9
      mg/L, respectively), and strains B. trispora 18(+) and 184(-)-beta-carotene (6.2%
      in dry biomass or more 2.5 g/L) without illumination in shake flasks. It is the
      first example of high constitutive production of the carotenoids by the
      representative of genus Streptomyces without photoinduction or increased
      synthesis of sigma factor The improved strains of B. trispora 18(+) and 184(-)
      can be used for biotechnological production of beta-carotene in industrial
      conditions.

PMID- 24450180
TI  - Antistaphylococcal action of lacto- and bifidobacteria and interleukn-2.
AB  - Antistaphylococcal action of Lactobacillus delbrueckii subsp. bulgaricus IMV B
      7281, L. acidophilus LMV B-7279 and Bifidobacterium animalis VKB as well as
      interleukin-2 (IL-2) has been determined on the model of experimental
      staphylococcal infection in mice. It has been established that peroral
      administration of certain probiotic strains of lacto- and bifidobacteria or
      composition L. acidophilus LMV B-7279--L. delbrueckii subsp. bulgaricus IMV B
      7281 with IL-2 to mice favored the reducing of terms of staphylococcus
      persistence in the kidneys of experimental mice. The studied schemes are
      promising for treatment of patients with surgical infection.

PMID- 24450181
TI  - [Curtobacterium flaccumfaciens pv. flaccumfaciens is the agent of bacterial
      disease of soybean].
AB  - A new phytopathogen has been identified and investigated as a result of ecosystem
      monitoring of bacterial soybean diseases in Ukraine which is identified as
      Curtobacterium flaccumfaciens pv. flaccumfaciens according to its phenotypic and
      genotypic characteristics. The pathogen is highly aggressive to soybean and can
      potentially be a threat of infection to other legumes.

PMID- 24450182
TI  - [Antifungal and antiviral substances of Pseudomonas chlororaphis subsp.
      aureofaciens strains--components of gaupsin].
AB  - Phenazine-1-carboxylic, 2-hydroxy-phenazine-carboxylic acid and 2-hydroxy
      phenazine active against phytopathogenic fungi were detected in fermentation
      broth of Pseudomonas chlororaphis subsp.aureofaciens strains UCM B-111 and UCM B
      306--components of insectofungicide biopreparation gaupsin using chromato-mass
      spectrometric methods; strain B-306 produced antifungal antibiotic pyrrolnitrin
      together with phenazines. Supernatants of fermentation broth of P chlororaphis
      subsp. aureofaciens B-111 and B-306 strains grown in King A medium and
      exopolymers preparations obtained from these supernatants using evaporation,
      dialysis and liophylisation were highly active against tobacco mosaic virus
      (TMV). At a dose of 10 mg/ml they reduced TMV infectivity by 76-96%, at
      concentrations 1 and 0.1 mg/ml the antiviral effect was decreased to 40-62 and 14
      27%, respectively. Dialysis did not influence the antiviral activity of isolated
      preparations. The latter contained 2-7.6 % of carbohydrates including neutral
      monosaccharides: fucose, mannose, galactose and glucose.

PMID- 24450183
TI  - [Biological properties of opportunistic microorganisms--agents of acute
      intestinal infections].
AB  - The etiological role of conditionally pathogenic bacteria in acute intestinal
      infections in the Sumy region has been studied. It is established, that the
      strains of Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter cloacae
      isolated from patients with acute intestinal infection were characterized by
      phenotypic heterogeneity. In 85.0 +/- 5.6% of the studied strains of K.
      pneumoniae, 30.0 +/- 7.2% of E. cloacae, 20.0 +/- 5.6% S. Aureus the authors have
      identified pathogenicity factors, which ensure their ability to adhesion and
      persistence (antiinterferon and anticomplement activity).

PMID- 24450184
TI  - [Characteristics of toxigenic properties of Myrothecium cinctum (Corda) sacc.,
      1886 and Myrothecium commune pidopl., 1969].
AB  - The comparative study of toxigenic potential of Myrothecium cinctum (12 strains)
      and Myrothecium commune (7 strains) was conducted. The ability to produce the
      complex of macrocyclic trichothecenes (MCTC) presented in ethanol soluble
      fraction (ESF), as well as fungistatic activity against yeasts test-cultures
      (strains Saccharomyces vini "Feodosia" and Candida stellatoidea 62) and rabbit
      skin test were evaluated. It was established that ESF output varied within wide
      limits in all studied strains of both species but it was significantly lower in
      M. commune strains. Higher ESF yields were accompanied as a rule by higher
      fungistatic activity and skin reaction in rabbits. The separate strains showed
      high biological activity with minor ESF output that could be possible caused by
      domination of more toxic components in complex preparation. The study of MCTC
      component structure by high performance liquid chromatography method (HPLC)
      showed with a few exceptions the presence of verrucarins A and J, roridins A, E,
      and H as well as unidentified components whose column retention times were 2.1
      and 4.9 minutes. The production of roridin H and unknown component with 2.1 min.
      retention time was typical of M. cinctum strains while verrucarin A and
      unidentified component with 4.9 min. retention time was typical of M. commune
      strains.

PMID- 24450185
TI  - [Production of inhibiting plant growth and development hormones by pathogenic for
      legumes Pseudomonas genus bacteria].
AB  - It has been studied the ability of pathogenic for legumes pathovars of
      Pseudomonas genus to produce ethylene and abscisic acid in vitro. A direct
      correlation between the level of ethylene production by agent of bacterial pea
      burn--Pseudomonas syringae pv. pisi and level of its aggressiveness for plants
      has been found. It is shown that the amount of abscisic acid synthesized by
      pathogenic for legumes Pseudomonas genus bacteria correlates with their
      aggressiveness for plants.

PMID- 24450186
TI  - [Cellulolytic activity of Fenellia flavipes and Fusarium oxysporum strains].
AB  - The production of cellulolytic enzymes by Fenellia flavipes and Fusarium
      oxysporum strains in submerged culture with plant residues as carbon source was
      studied. It was established that the majority of studied strains was able to
      hydrolyze the filter paper, husk of sunflower seeds, wheat straw and corn stalks.
      The ability to synthesize enzymes depended on the strain of microscopic fungi,
      type of substrate and duration of cultivation. As a result two fungal strains
      were selected: F. flavipes 655 with maximum of cellulolytic activity 2 U/ml in
      the medium with wheat straw and 1.6 U/ml in the medium with corn stalks on the
      4th day of cultivation and F. oxysporum 420 which synthesized 0.875 mg/ml of
      reducing sugars.

PMID- 24450187
TI  - [Peculiarities of mortmass mycobiota formation in soft-deciduous young forests on
      old-tillage soils of the Chernihiv Polissya].
AB  - Thirty eight species of fungi were identified as a result of mycological analysis
      of 180 mortmass samples of Betulapendula Routh. and Populus tremula L. Mortmass
      mycobiota of B. pendula and P. tremula was represented by white, brown- and soft
      rot species. Fungi of Ascomycota phylum were most numerous (24 species). Species
      of genera Aspergillus, Penicillium, Brachysporium, Cladosporium, Drechslera,
      Fusarium, Cylindrocarpon, Spadicesporium, Trichoderma in variants with middle and
      hard classes of wood degradation were identified among them. The Basidiomycota
      phylum was represented by 12 species; among them Armillariella mellea and
      Phellinus igniarius occurred most frequently. The most specific fungal complex
      decaying B. pendula and P tremula mortmass was observed under class III of its
      degradation.

PMID- 24450188
TI  - [Properties of pectolitic phytopathogenic bacteria isolates obtained in Ukraine].
AB  - Bacteria obtained from potato tubers having symptoms of soft rot and grown in
      different regions of Ukraine are identified as Pectobacterium carotovorum subsp.
      carotovorum. These bacteria strains are able to produce bacteriocines. Their
      killer activity in respect of P. carotovorum and Esherichia coli has been
      studied. The sensitivity to bactericines has been shown. Purified fractions of
      bacteriocines having high molecular weight (MCTV) have been obtained. The
      difference in composition of proteins from phage tails as compared to the ones in
      P. carotovorum J2 has been studied by the method of electrophoresis. It was found
      that the composition of MCTV major proteins of studied isolates mostly
      corresponds to P. carotovorum J2. The set of enzyme minor fractions has some
      different compositions as compared to P. carotovorum J2. It has been hypothesized
      that this difference is responsible for killer specificity.

PMID- 24450189
TI  - New approach for identification of bacteriophage virion structural proteins.
AB  - The ability of the phage structural polypeptides to undergo post-translational
      modification makes the task of correlation of the primary nucleotide sequence
      data with the actual structural proteins of a virion extremely challenging. This
      study describes an alternative model approach based on two-stage chromatography
      for allocation of virion structural components and identification of their major
      polypeptides. Bacteriophage T4D, its amber mutant T4D23 (amH11) and its tail
      preparations were purified, concentrated and separated by ion exchange
      chromatograpgy based on fibrous DEAE-cellulose. The major tail fraction was then
      exposed to size-exclusion chromatography which enabled to separate tail
      components by size. This method proved itself as a highly efficient and gentle
      enough to save most of the biological material without changing the basic
      properties of the native phage. The result also shows that the accumulation of
      individual phage tails in the course of the amber mutant T4D23 (amH11)
      propagation on the permissive host Escherichia coli CR63 was resulted by changes
      in the conditions of reproduction. The ability of bacteriophages to form an
      excess of tails, capsids and other structures during reproduction on a non
      traditional host provides an alternative way for obtaining highly concentrated
      preparations of virion components for further analysis of their major proteins
      and determination of the genes responsible for their synthesis.

PMID- 24450190
TI  - [Effect of mutations in lawc/Trf2 gene on development of chromocenter and
      chromosome disjunction in Drosophila melanogaster].
AB  - In Drosophila, one of the genes of the lawc/Trf2 (leg-arista-wing complex/TBP
      related factor 2) complex encodes an alternative basic transcription factor
      homologous to the TRF2 protein in vertebrates and human and belongs to a
      conservative Tbp (TATA box-binding protein) gene family. In the present study,
      reasons for the high frequency of chromosome nondisjunction were studied among
      descendants of mutants from 18 lines with a decreased expression of the TRF2
      protein. It was determined that the suppression of the TRF2 expression violates
      the development of a compact chromocenter and the correct approach of homologous
      chromosomes (in germinative and somatic cells). The possibility of the
      participation of TRF2 in the evolutionary genetically programmed process of sex
      ratio violation, which is typical of a number of animal species, is discussed.

PMID- 24450191
TI  - [Dominance status of shape of male genitalia in interspecific crosses of some
      Drosophila virilis group species].
AB  - The heritability of the shape of the main species-specific morphological trait
      for the Drosophila virilis group--the male mating organ has been analyzed using
      the hybrid males D. virilis x D. lummei and D. virilis x D. novamexicana. The
      results suggest an increase in the share of the characters with a recessive
      status in the evolutionarily younger species and demonstrate the role of sex
      chromosomes in the implementation of a dominant or recessive status of the trait.
      The roles of additive and epistatic components of the total variation in the
      evolution of dominance status, shown in several known theoretical models and
      confirmed by our data, are considered. The published data on sterility of hybrid
      males in interspecific crosses are discussed from the standpoint of the evolution
      of dominance.

PMID- 24450192
TI  - [Effect of disruption of Pichia pastoris YPS1 gene on viability and production of
      recombinant proteins].
AB  - In the present study, we constructed a Pichia pastoris mutant strain PS111 that
      lacks one member of the yapsin family through disruption of the YPS1 gene coding
      for aspartic protease yapsin 1. Under normal growth conditions, the PS111 mutant
      strain did not show detectable growth defects. Unlike the S. cerevisiaeyps1
      mutant, the P. pastoris PS111 strain showed no sensitivity when grown in the
      presence of CaCl2, elevated temperature (37 degrees C), under acid (pH 4.9) and
      alkaline (pH 8.3) conditions. Unlike the S. cerevisiae, the P. pastoris yps1
      mutant showed decreased growth phenotype induced by cell wall-perturbing reagent
      sodium dodecyl sulfate (SDS) only when the concentration of SDS was increased by
      ten times. The use of the yps1 disruptant to produce human interferon alpha 16
      (hINF-alpha 16) prevents proteolysis, which occurs in the wild-type strain. It
      was found that the degradation of recombinant protein Alburon composed of human
      serum albumin (HSA) and hINF-alpha 16 was slightly decreased in the strain
      lacking yapsin 1.

PMID- 24450193
TI  - [Phylogenetic analysis of the genes for naphthalene and phenanthrene degradation
      in Burkholderia sp. strains].
AB  - The genetic systems responsible for naphthalene and phenanthrene catabolism have
      been analyzed in the five strains of Burkholderia sp. isolated from soil samples
      (West Siberia) contaminated by heavy residual fuel oil and in the strain
      Burkholderia sp. BS3702 from the laboratory collection isolated from soil samples
      of the coke gas works (Vidnoe, Moscow oblast). The results of this work
      demonstrate that naphthalene and phenanthrene degradation in the above strains is
      encoded by the sequences not homologous to the classical nah genes of
      pseudomonades. In the Burkholderia sp. BS3702 strain, the initial stages of
      phenanthrene degradation and the subsequent stages of salicylate degradation are
      controlled by the sequences of different evolutionary origins (phn and nag
      genes).

PMID- 24450194
TI  - [Chromosome variability in grape (Vitis amurensis Rupr.) cells transformed with
      plant oncogene rolB].
AB  - The numbers of chromosomes and nucleoli in cultured cells of Vitis amurensis
      transformed with the rolB oncogene from A. rhizogenes have been studied. In
      general, the integration of the rolB gene in grape DNA mostly caused the
      elevation of the level of the chromosome variability, as well as higher numbers
      of nucleoli in the cultured cells. The possible influence of the observed
      chromosomal modifications on the productivity parameters of the grape cell
      cultures is discussed.

PMID- 24450195
TI  - [Phylogeny of salmonids (Salmoniformes, Salmonidae) and molecular dating:
      analysis of mtDNA data].
AB  - Phylogenetic relationships among 41 species of salmonid fish and some aspects of
      their diversification-time history were studied using the GenBank and original
      mtDNA data. The position of the root of the Salmonidae phylogenetic tree was
      uncertain. Among the possible variants, the most reasonable seems to be that in
      which thymallins are grouped into the same clade as coregonins and the lineage of
      salmonins occupied a basal position relative to this clade. The genera of
      Salmoninae formed two distinct clades, i.e., (Brachymystax, Hucho) and (Salmo,
      Parahucho, (Salvelinus, Oncorhynchus)). Furthermore, the genera Parasalmo and
      Oncorhynchus were reciprocally monophyletic. The congruence of Salmonidae
      phylogenetic trees obtained using different types of phylogenetic markers is
      discussed. According to Bayesian dating, ancestral lineages of salmonids and
      their sister esocids radiated about 106 million years ago. Sometime after,
      probably 100-70 million years ago, the salmonid-specific whole genome duplication
      took place. The divergence of salmonid lineages on the genus level occurred much
      later, within the time interval of 42-20 million years ago. The main wave of the
      diversification of salmonids at the species level occurred during the last 12
      million years. The possible effect of genome duplication on the Salmonidae
      diversification pattern is discussed.

PMID- 24450197
TI  - [Fish growth hormone genes: divergence of intron sequence in charrs of Salvelinus
      genus].
AB  - Sequences of the two large introns (C and D) from two paralogous growth hormone
      genes, GH1 and GH2, were compared in eight charr species of the Salvelinus genus
      (Osteichthes, Salmonidae). It was demonstrated that the rates of intron
      divergence in these two genes were remarkably different. Introns in the GH1 gene
      appeared to be more conservative, while the rate of intron variations was
      considerably higher in the GH2 gene. These data suggest that noncoding regions of
      nuclear genes are shaped by selective pressure. The lower congruence of
      phylogenetic scheme constructed based on an analysis of the GH1 introns compared
      to that based on the GH2 data, as well as with the traditional views on the
      evolution of charr species, also favors the supposition on contrasted patterns of
      selective pressure in noncoding intronic sequences.

PMID- 24450196
TI  - [Intraspecific genetic differentiation of the Siberian Rubythroat (Luscinia
      calliope): data of sequencing the mtDNA cytochrome b gene].
AB  - For the first time, genetic diversity and intraspecific subdivision of Luscinia
      calliope was studied according to the data of the mtDNA cytochrome b gene
      sequencing. The strong differentiation of haplotypes of the Siberian Rubythroat
      into western and eastern groups, which include subspecies according to their
      geographical attachment, was revealed. A high-haplotypic (Hd = 0.986) and
      nucleotide (pi = 0.00875) variety was shown for the species as a whole. We
      revealed considerable genetic distances (pi = 0.016) between the western and
      eastern haplotypes that were four times higher than the intraspecific distances
      in terms of cytochrome b for passerines (D = 0.004). For three birds from
      Transbaikal, significant genetic divergence was detected, which could indirectly
      indicate the existence of the transition zone of several subspecies in this part
      of the area.

PMID- 24450198
TI  - [Analysis of microsatellite loci variations in herring (Clupea pallasii
      marisalbi) from the White Sea].
AB  - The genetic diversity among spawning groups of herring from different parts of
      the White Sea was assessed using ten microsatellite loci. All loci were
      polymorphic with the expected heterozygosity estimates varying in the range of
      12.7-94.1% (mean was 59.5%). The degree of genetic differentiation displayed by
      White Sea herring was statistically significant (theta = 2.03%). The level of
      pairwise genetic differentiation F(ST) was 0-0.085, and it was statistically
      significant in most of the comparison pairs between the herring samples. A
      hierarchical analysis of molecular variance (AMOVA) revealed the statistically
      significant differentiation of White Sea herring. 96.59% genetic variation was
      found within the samples and 3.41% variation was found among the populations. The
      main component of interpopulation diversity (1.85%) falls at the differences
      between two ecological forms of herring, spring- and summer-spawning. Within the
      spring-spawning form, the presence of local stocks in Kandalaksha Gulf, Onega
      Bay, and Dvina Bay was demonstrated.

PMID- 24450199
TI  - [Association of YWHAE gene polymorphism with suicidal behavior].
AB  - The importance of YWHAE gene polymorphisms (rs1532976, rs3752826, and rs9393) in
      the development of suicidal behavior has been studied in ethnic groups of
      Russians and Tatars from the Republic of Bashkortostan. It was revealed that the
      carriers of the YWHAE*C allele of rs3752826 polymorphism of the YWHAE gene have
      increased the risk of suicidal behavior (OR = 1.91), regardless of their
      ethnicity. In addition, the YWHAE*T allele of rs9393 polymorphism (OR = 2.21),
      YWHAE*T/*T genotype (OR = 2.73), and YWHAE*T allele (OR = 1.52) of the rs1532976
      polymorphism, as well as the YWHAE*A*T haplotype of rs1532976 and rs9393
      polymorphisms (OR = 1.54) represent genetic markers of the risk of suicidal
      behavior in the sample of subjects of Russian ethnicity.

PMID- 24450200
TI  - [New mutations in low-density lipoprotein receptor gene in familial
      hypercholesterolemia patients from Petrozavodsk].
AB  - Using an automated fluorescent single-strand conformation polymorphism (SSCP)
      analysis of the entire coding region, promoter zone, and exon-intron junctions of
      the low-density lipoprotein (LDL) receptor gene, we examined 80 DNA samples of
      patients with familial hypercholesterolemia (FH) from Petrozavodsk. We revealed
      mutations that might cause FH in five probands, including FH-North Karelia (c.925
      931del7) mutation and four previously unknown mutations. These novel mutations
      included a transversion (c.618T>G (p.S206R), one nucleotide insertion
      c.195_196insT (p.FsV66:D129X), a complex gene rearrangement c.192del10/ins8
      (p.FsS65:D129X), and a single nucleotide deletion c.2191delG (p.FsV731:V736X).
      Three out of four novel mutations produce an open reading frame shift and the
      premature termination of translation. An analysis of the cDNA sequence of the LDL
      receptor showed that this might result in the formation of a transmembrane-domain
      deficient receptor that is unable to bind and internalize the ligand. Our results
      suggest the absence of a strong founder effect associated with FH in the
      Petrozavodsk population.

PMID- 24450201
TI  - [Genetic control of protein synthesis of white lupine (Lupinus albus L.) seeds].
AB  - Using polyacrylamide gel electrophoresis in the glycine-acetic acid system (pH
      3.2), variants of proteins of white-lupine seeds were revealed. The study of
      conglutin polymorphism in the culture of the autogamous population F(-->
      infinity) (var. Dega) revealed two loci, Con A and Con B, which control protein
      synthesis. The loci were situated in the same linkage group within a distance of
      11.48 +/- 3.4% of recombination. Natural selection in favor ofgenotypes that
      contain Con A1 Con B2 alleles is proposed. It is established that conglutins A
      and B (CON A and CON B) contain cysteine residues, which form intermolecular
      disulfide bonds between peptides.

PMID- 24450202
TI  - [Methylation profile of INK4B-ARF-INK4A locus in atherosclerosis].
AB  - Single-nucleotide polymorphisms (SNPs) in the 9p21.3 locus have recently been
      demonstrated to be strongly associated with the risk of developing human
      atherosclerotic lesions. However, the pathophysiology of this locus is
      insufficiently studied. Here, the methylation profile of the nearest mapped genes
      for cyclin-dependent kinase inhibitors CDKN2A (p16(INK4a), p14(ARF)) and CDKN2B
      (p15(LNK4b)) in the tissues of the carotid artery in patients with
      atherosclerosis was evaluated for the first time. Aberrant DNA methylation of the
      analyzed loci was not established in either the atherosclerotic plaques and in
      the tissues from the macroscopically unchanged previa vascular wall in the same
      patients.

PMID- 24450203
TI  - [Transfer of mitochondrial DNA to nuclear genome of cells of passaged cell line
      of Drosophila virilis].
AB  - The variability of the chromosomal fragments of the atp6 mitochondrial gene,
      which is integrated into chromosomal DNA in the lines of flies of different
      geographic origins and in the passaged cell lines of D. virilis has been
      analyzed. We did not reveal any nucleotide variability in this DNA marker among
      the studied fly lines. This result is consistent with the proposition that the D.
      virilis species is monomorphic. The new fragments of the atp6 gene that are
      associated with the insertions of the Tv1 retrotransposon and are absent in the
      fly genome are revealed in the genome of the passaged cell line of D. virilis.
      This fact is evidence of the activation of the mitochondrial DNA transfer into
      the nuclear genome of the cells of passaged cell culture.

PMID- 24450204
TI  - [Influence of ionizing radiation on the parameters of oxidative stress markers in
      the rat liver and thymus].
AB  - Influence of ionizing radiation on the parameters of oxidative stress markers in
      the liver and thymus of the rats exposed to gamma-radiation 60Co at a doze of 4
      Gy was investigated. The animals were decapitated on the 1, 4, 7, 10, 14, 22 and
      30th day after irradiation and cell suspensions from the liver and thymus were
      obtained. After centrifugation, the content of MDA, the spontaneous and NADH
      induced synthesis of superoxide anion radical of oxygen, the content of total and
      free iron were determined in the cellular sediment and centrifugate containing
      intercellular fluid. It is shown that the content of MDA and the levels of
      spontaneous and NADH-induced synthesis of superoxide anion radical of oxygen
      increases in intercellular fluid and thymus and liver cells on the 1st day after
      radiation exposure. In the liver, these parameters are normalized by the 4th day
      and do not significantly differ from the control level in the period of time
      following radiation exposure. In thymus, as compared with liver, the level of
      oxidative stress parameters increases by the 4th day after radiation and remains
      at the raised level within 22 days after irradiation exposure. It is shown that
      the content of free iron in thymus cells of irradiated animals increases 3.6
      times by the 4th day and reliably exceeds the control level within the next 22
      days. Radiation does not lead to any changes in the content of free iron in liver
      cells. Different levels of the free iron content can serve the reason for various
      sensitivity of oxidative stress markers in thymus and liver cells to radiation
      exposure.

PMID- 24450205
TI  - [An assessment of relative contribution of DNA reparation and glutathione
      dependent pathway of detoxification in response of Chlorella algae to uranium].
AB  - Toxicity of 238U (as uranyl nitrate) in the range of 0.04-84 micromol/L for
      Chlorella (Chlorella vulgaris Beijerink) was investigated. The best approximation
      for relationship between the toxic effect in Chlorella and 238U Concentrations is
      observed using the hormetic Brain-Cousens model. A significant increase in
      Chlorella biomass, estimated as the optical density of suspension, as well as the
      level of fluorescence of chlorophyll was observed in the range of 17-29
      micromol/L with the maximum at a 23 micromol/L. It was found that 38 micromol/L
      of 238U induced a significant toxic effect; while at 53 micromol/L inhibition of
      Chlorella biomass by 50% was observed. According to our observations, the toxic
      effect of low concentrations of 238U was increased in the presence of 0.02
      micromol/L caffeine (used as inhibitor of DNA repair processes) or DL-buthionine
      (S, R)-sulfoximine (used as a selective inhibitor of the key glutathione
      biosynthetic pathway).

PMID- 24450206
TI  - [Non-mutagenic non-targeted radiation effects. Determined decrease of cells
      viability in populations induced by low dose radiation].
AB  - Experimental data obtained from studies on the objects with different
      organization were analyzed. These data expand the ideas about the phenomenon of
      "viability determinate decrease in offspring of irradiated cells" discovered in
      the 1970s. This phenomenon was evaluated according to the standpoint of modern
      radiobiology. It is postulated that the studied effects, which are associated
      with the cytoplasmic structures damage and are clearly manifested in mammalian
      low proliferative tissues, can be significant for humans in connection with the
      delayed somatic consequences of low dose irradiation, as well as with a more
      general problem of longevity reduction. Possibility of inheritance ofthese
      alteration in protozoa asexual reproduction and metazoan sexual reproduction
      (generation F1) is demonstrated.

PMID- 24450207
TI  - [Genetic and cytogenetic predictors of human chromosomal radiosensitivity].
AB  - We studied association between the frequencies of gamma-induced (1 Gy in vitro)
      chromosome aberrations in blood lymphocytes and polymorphism of 45 repair
      candidate genes, detoxification and oxidative stress genes (53 sites) for 99
      healthy volunteers. The levels of chromosome-type aberrations correlated with
      carriage of the minor alleles of the genes OGG1 Ser326Cys, ABCB1 Ile1145 = and
      NQO1 Pro187Ser (p = 0.0002). We have shown that all the revealed genetic
      associations were less effective in predicting chromosomal radiosensitivity as
      compared to the correlations between spontaneous and gamma-induced aberrations (p
      = 1.0 x 10(-6)). The addition of genetic markers to cytogenetic predictors
      improved the predictive accuracy for chromosomal radiosensitivity with the
      multiple correlation coefficient reaching R = 0.58 (p = 3.1 x 10(-8)). Thereby we
      were able to explain more than 30% of the population variability in chromosomal
      radiosensitivity.

PMID- 24450208
TI  - [The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and
      fast neutrons].
AB  - The effectiveness of fractionated exposure to gamma- and neutron radiation in
      their separate and combined use on the growth and functional morphology of mutant
      p53 sarcoma M-1 in rats was studied. Investigation techniques included
      immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic
      activity and apoptotic death of tumor cells, as well as computer analysis of
      microscopic images. The antitumor efficacy of different types of radiation is
      shown to be determined by different levels of apoptosis induction, reduced
      proliferation and cellularity. Neutron radiation of the impulse generator has a
      marked damaging effect on the vasculature and the development of tumor necrosis.
      Fractionated irradiation at equal daily doses led to the decrease in the relative
      effectiveness of radio-inactivation of tumor cells. After 9 fractions of
      irradiation, the calculated value of the RBE of fast neutrons normalized to the
      input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced
      proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7
      and 3.1, respectively. In the mode of daily superfractionation with splitting the
      dose in two fractions, the effectiveness of the combined exposure corresponded to
      the additive effect of gamma- and neutron radiation with a tendency toward
      synergism. There are reasons to believe that high resistance of sarcoma M-1 to
      the ionizing radiation impact is due not only to a fraction of hypoxic cells, but
      also the mutant status of p53 gene.

PMID- 24450209
TI  - [Recombinant thrombopoietin antiradiation therapeutic effectiveness evaluation on
      dogs according to hemopoiesis and survival criteria].
AB  - Recombinant human thrombopoietin (rh TPO) has been investigated as a means of
      acute radiation disease urgent treatment in the experiments on 24 mongrel dogs.
      The animals were exposed to total acute gamma-irradiation at the doses of 3.5 Gy
      (exceeding LD50/45 under our conditions) and 3 Gy. All the dogs including control
      ones received antibiotics Ampicillin and Gentamicin twice a day during the acute
      period from the 7th to the 21st day. TPO was injected one time s/c or i/v at the
      doses of5 or 10 mkg/kg 1.5-2 h after exposure. TPO at a dose of 5 mkg/kg was
      ineffective. TPO at a dose of 10 mkg/kg had a positive effect on the kinetics of
      blood forming units, especially platelets (nadir, restoration rate) in terms of
      the 45-day survival. As a result, in TPO groups, nadir averaged at both exposure
      doses on leucocytes (1.3-1.4) x 10(9)/l vs (0.70-0.75) x 10(9)/l in control
      groups and on thrombocytes (102-112) x 10(9)/l vs (44-33) x 10(9)/l in control
      ones. Despite the low number of animals in experimental groups, the results
      permit to regard rhTPO as a worth-while urgent therapeutic means for the acute
      radiation damage treatment and preventing thrombopenia.

PMID- 24450210
TI  - [The influence of consecutive application of radioprotector B-190 and interleukin
      1beta on changes of number of peripheral blood leucocytes and functional status
      of neutrophils of irradiated mice].
AB  - The estimation of efficiency of consecutive application of radioprotector B-190
      and interleukin-1beta administered at early times after acute irradiation by
      studying the changes of the number of peripheral blood leukocytes, neutrophils
      and lymphocytes, as well as cytochemical research into the contents of glycogen,
      myeloperoxidase and alkaline phosphatase in neutrophils of the irradiated mice
      was carried out. It is established that administration of radioprotector B-190 at
      a doze of 50 mg/kg for 15 minutes before irradiation and interleukin-1beta at a
      doze of 50 mkg/kg for 15 minutes after irradiation reduces the expressiveness of
      post-irradiation leukopenia, accelerates restoration of the number of neutrophils
      and lymphocytes in peripheral blood, normalizes the functional status of
      neutrophils of irradiated mice to a greater degree than their isolated
      introduction.

PMID- 24450211
TI  - [Effects of iron ion additional introduction in radiation therapy of tumor
      bearing animals].
AB  - The gender differences of the transplantable glioma-35 growth were revealed in
      tumor-bearing rats. The effect of mineral iron containing water (ICW) as drinking
      water was studied during radiation therapy (RT) in tumor bearing male rats. It
      was shown that ICW used separately had a weak anti cancer effect. The ICW use
      after irradiation caused no significant changes in hematological reactions as
      compared with RT only. The mineral water administration before irradiation
      resulted in the reduction of the supercoiled DNA index on the 1st and 21st day
      after irradiation, as well as in monocytopeny and a definite decrease in the
      tumor volume on the 21st day of the experiment as compared with control, which is
      associated with the ferroptosis effect of ICW. It was established that the
      reaction peculiarities of the blood DNA structure index in irradiated rats at the
      early stage of glioma growth may serve an express marker of the efficiency of RT.

PMID- 24450212
TI  - [Effect of microwaves on Chlamydomonas actinochloris culture in the stationary
      phase of growth].
AB  - Effects of the microwave radiation on the culture of Chlamydomonas actinochloris
      green flagellar alga in the stationary phase of growth are studied. After
      exposure to radiation at the maximum dose of 125 J/g, the cell functional state
      worsened but all the studied parameters were restored in 20 days and in the long
      run found to be even better than the control indices. The data are compared with
      the similar ones obtained earlier for the lag phase culture. The studied sample
      is found to be more resistant to the irradiation than the previous one.

PMID- 24450214
TI  - ["The phenomenon of life". Selected works. In two volumes. Moscow: Nauka, 2010
      2012].

PMID- 24450213
TI  - [Function of the thyroid gland of tundra voles living on sites with the increased
      natural radioactivity].
AB  - We studied a functional condition of the thyroid gland of tundra voles living on
      sites with the increased level of a natural radioactivity (in Republic Komi areas
      in Russia). We have revealed that the functional condition of the thyroid gland
      depends on the phase of the population cycle of animals. The level of thyroid
      hormones in the irradiated animals differed from the norm; a high concentration
      of hormones in the irradiated animals was observed in the phase of the maximum
      number of animals, while males and females showed multidirectional differences
      from the control in the phase of the decreased number of animals.

PMID- 24450215
TI  - [The main results of scientific research in the field of radiobiology and
      radioecology for 2012].

PMID- 24450216
TI  - [XLI radiological readings in memory of V.M. Klechkovskiy].

PMID- 24450217
TI  - [Vladimir Leonidovich Svidersky (1931-2013)].

PMID- 24450218
TI  - [Formation of cortical inhibition in ontogenesis].
AB  - Analysis of literature data about development of cortical inhibition allows
      suggesting that synaptical inhibition of cerebral cortex neurons begins to be
      realized almost simultaneously with beginning of their generation of background
      activity. From the moment of the appearance of inhibitory processes there have
      been functioning all kinds of cortical inhibition. Thereby, the main mechanisms
      realizing cortical inhibition in the mature cerebral cortex begin functioning
      from the moment of its inclusion in ontogenesis.

PMID- 24450219
TI  - [Composition and content of carotenoids in body of the Black Sea gastropod
      mollusc Rapana venosa (Valenciennes, 1846)].
AB  - There were studied content and composition of carotenoids in body of the Black
      Sea gastropod mollusc Rapana venosa. To separate and identify this group of
      compounds, methods of thin layer and high performance liquid chromatography, mass
      spectra and spectra in UV-VIS range were used. There were identified 84-87% of
      carotenoids. The main proportion belonged to mytiloxanthine--28-30%. The rest-
      pectenolon, diatoxanthin, alloxanthin--accounted for 10-15% of the total content
      except for beta-carotene--3-4%. The fraction is also isolated which contains
      complex esters of pectenolon, diatoxanthin, alloxanthin, and mytiloxanthin. It
      amounts to 17-20 % of pigments of carotenoid line. Minor components were not
      determined. Pathways of metabolic transformation of carotenoids in tissues of R.
      venosa are considered on the basis of study of the trophic system "mollusc
      filtrator--mollusc-predator" by the example of Mytilus galloprovincialis and R.
      venosa.

PMID- 24450220
TI  - [Phosphoethanolamine in the brain of the eurythermal pond fish Perccottus glehni
      (Eleotridae, Perciformes, Dyb. 1877) as a phenomenon depending on temperature
      factor].
AB  - Effects of a seasonal decrease of environmental temperature and cold shock on
      pools of free amino acids (FAA) was studied in brain of the eurythermal pond fish
      P. glehni. It is for the first time that in the brain of eurythermal animals the
      nonprotein amino acid phosphoethanolamine (PEA) was revealed. It was found there
      in a large amount only under conditions of near-zero temperatures. It was shown
      that in the P. glehni brain, as a result of the seasonal decrease of temperature,
      the PEA pool rose intensively from 0.3 % at the summer period to 33.6 % in
      winter. On the contrary, the brain taurine pool that in the summer was the
      highest as compared with other FAA (29.0% of the total pool) decreased to 8.9% by
      the beginning of the winter period. The same negative correlation of the taurine
      and PEA amounts was found under action of acute cold shock (+1 degree C):
      throughout 4 days the taurine level also decreased from 32.2 to 14.5% of the
      total pool, whereas the PEA level rose swiftly (from 2.1 to 15.3%). Both kinds of
      the low temperature action led, apart from PEA, to an intensive increase of the
      serine pool and accumulation of phosphoserine. Role of PEA in biochemical
      evolution and adaptation of brain to low temperatures is discussed. It is
      suggested that accumulation of PEA, phosphoserine, and serine is associated with
      a change of the status of phospholipids of membrane at low temperatures.

PMID- 24450221
TI  - [Comparative enzymological study of catalytic properties of sturgeon fish liver
      monoamine oxidases].
AB  - We performed comparative study of substrate and inhibitor specificity of liver
      monoamine oxidases (MAO) of the giant sturgeon Huso huso, starred sturgeon
      Asipenser stellatus, Persian sturgeon Asipenser persicus, and Russian sturgeon
      Asipenser gueldenstaedtii. Results of the substrate-inhibitor analysis with use
      of inhibitors chlorgilin and deprenil, as well as of five specific substrates
      indicate homogeneity of these enzymes. All studied MAO have several orders higher
      sensitivity to chlorgilin than that to deprenil, the essential interspecies
      differences being observed. There are determined kinetical parameters of
      enzymatic deamination (K(M) and V) of tyramine, serotonin, noradrenalin,
      benzylamine, beta-phenylethylamine, and N-methylhistamine. It is found that all
      studied enzymes show the higher activity toward serotonin and noradrenalin-
      substrates of the MAO form A, as compared with benzylamine, beta
      phenylethylamine, and N-methylhistamine--substrates of the MAO form B of mammals,
      the maximal activity being shown by enzyme of the giant sturgeon.

PMID- 24450222
TI  - [Auditory aftereffects with approaching and withdrawing sound sources: dependence
      on trajectory and domain of presentation of adapting stimuli].
AB  - The perceptual peculiarities of sound source withdrawing and approaching and
      their influence on auditory aftereffects were studied in the free field. The
      radial movement of the auditory adapting stimuli was imitated by two methods: (1)
      by oppositely directed simultaneous amplitude change of the wideband signals at
      two loudspeakers placed at 1.1 and 4.5 m from a listener; (2) by an increase or a
      decrease of the wideband noise amplitude of the impulses at one of the
      loudspeakers--whether close or distant. The radial auditory movement of test
      stimuli was imitated by using the first method of imitation of adapting stimuli
      movement. Nine listeners estimated the direction of test stimuli movement without
      adaptation (control) and after adaptation. Adapting stimuli were stationary,
      slowly moving with sound level variation of 2 dB and rapidly moving with
      variation of 12 dB. The percentage of "withdrawing" responses was used for
      psychometric curve construction. Three perceptual phenomena were found. The
      growing louder effect was shown in control series without adaptation. The effect
      was characterized by a decrease of the number of "withdrawing" responses and
      overestimation of test stimuli as approaching. The position-dependent
      aftereffects were noticed after adaptation to the stationary and slowly moving
      sound stimuli. The aftereffect was manifested as an increase of the number of
      "withdrawing" responses and overestimation of test stimuli as withdrawal. The
      effect was reduced with increase of the distance between the listener and the
      loudspeaker. Movement aftereffects were revealed after adaptation to the rapidly
      moving stimuli. Aftereffects were direction-dependent: the number of "withdrawal"
      responses after adaptation to approach increased, whereas after adaptation to
      withdrawal it decreased relative to control. The movement aftereffects were more
      pronounced at imitation of movement of adapting stimuli by the first method. In
      this case the listener could determine the starting and the finishing points of
      movement trajectory. Interaction of movement aftereffects with the growing louder
      effect was absent in all ways of presentation of adapting stimuli. With increase
      of distance to the source of adapting stimuli, there was observed a tendency for
      a decrease of aftereffect of approach and for an increase of aftereffect of
      withdrawal.

PMID- 24450223
TI  - [Effect of angiotensin-converting enzyme inhibitors, beta-adrenoblockers, and
      their combinations on survival and plasma catecholamine levels in rats with
      chronic heart failure with induced exacerbations].
AB  - By using model of chronic heart failure (CHF) occurring with induced
      decompensations, it was shown that inhibitors of angiotensin-converting enzyme
      (ACE) and beta-adrenoblockers promoted to different degree the correction of
      hypercatecholaminemia and an increase of survival of rats. The most pronounced
      effect was characteristic of beta-adrenoblockers atenolol, propranolol, and
      carvedilol. The lower activity was demonstrated by other adrenoblockers that had
      no intrinsic sympathomimetic activity, as well as captopril. However, positive
      effect of these drugs on rat survival occurred regardless of their action on the
      sympathoadrenal system. The ACE inhibitors, particularly hydrophilic lysinopril,
      to the lesser degree than beta-adrenoblockers, prevented death of animals at the
      period of the CHF decompensation. The combined use of ACE inhibitors with beta
      adrenoblockers, especially with carvedilol, promoted the maximally expressed
      decrease of the sympathoadrenal activity and an increase of the rat survival,
      including that at the CHF decompensation.

PMID- 24450224
TI  - [Encoding of wriggling call models by neuronal populations of the central nucleus
      of the midbrain posterior colliculus in house mouse (Mus musculus)].

PMID- 24450225
TI  - [Intranuclear iron localization in mammalian brain neurons].

PMID- 24450226
TI  - [Regulation of the destructive processes occurring in the body in senescence and
      in oncogenesis: a hypothesis].
AB  - A hypothesis has been suggested, according to which destruction of the body that
      occurs during senescence and carcinogenesis is likely to be regulated by the
      atavistic mechanism of apical dominance described by plant physiologists. This
      mechanism is inherited from the first on Earth multicellular animals that behaved
      the mode of life attached to benthos and to underwater objects and probably were
      modular sessile invertebrates.

PMID- 24450227
TI  - [To the memory of Boris Fedorovich Tolkunov 11.05.1930-03.05.2012].

PMID- 24450228
TI  - Questions for: Carrie Banahan.

PMID- 24450229
TI  - Bargain hunting in health care. Uncertainty over obamacare has caused an overly
      aggressive selloff in health-related real estate stock.

PMID- 24450230
TI  - Factors associated with cerebral malaria.
AB  - We conducted a retrospective unmatched case-control study using the medical
      records of patients admitted to the Hospital for Tropical Diseases, Mahidol
      University, Bangkok, Thailand to investigate factors associated with cerebral
      malaria. The records of 137 patients with severe Plasmodium falciparum without
      cerebral malaria and 35 patients with cerebral malaria hospitalized during 1997
      2005 were reviewed and compared. Ten factors associated with cerebral malaria
      were identified: pulmonary edema [odds ratio (OR)= 13.8; 95% confidence interval
      (CI): 1.3-143.2], splenomegaly (OR=3.7; 95% CI: 1.3-44.7), fever (OR=3.3; 95% CI:
      1.7-14.3), day 1 malarial density < or = 249,999/microl (OR=1.6; 95% CI: 1.1
      14.6), day 2 malarial density < or =249,999/microl (OR=3.4; 95% CI: 1.3-35.1),
      dyspnea (OR=1.4; 95% CI: 1.2-12.1), hepatomegaly (OR=1.8; 95% CI: 0.2-12.1),
      being a referred patient (OR=1.3; 95% CI: 1.0-2.2), a higher systolic blood
      pressure (OR=1.2; 95% CI: 1.0-2.1) and a higher body mass index (OR=1.6; 95% CI:
      1.0-2.6). Pulmonary edema was the strongest factor associated with cerebral
      malaria in our study. Clinicians who treat patients with severe Plasmodium
      falciparum malaria should be aware these factors are associated with cerebral
      malaria.

PMID- 24450231
TI  - Risk factors for and prevalence of clonorchiasis in Miaoli County, Taiwan.
AB  - The objective of this study was to investigate the risk factors for and
      prevalence of clonorchiasis in Miaoli County, Taiwan. In 2009, 6,929 subjects
      were randomly selected in Miaoli County and given a questionnaire to fill out
      regarding risk factors for clonorchiasis; the response rate was 69%. Stool sample
      was obtained from each participant who filled out the questionnaire and examined
      using the merthiolate-iodine-formaldehyde concentration (MIFC) technique to
      determine the presence and concentration of Clonorchis sinensis eggs. Fifty-one
      subjects gave a history of clonorchiasis (prevalence rate 0.7%). Seven stool
      samples were positive for C. sinensis (prevalence rate 0.1%). Shihtan Township
      (5.0%) in Miaoli County had the highest prevalence of clonorchiasis. Using
      logistic regression, we found people who often fished (OR: 3.65, p=0.013) or who
      had a family member with a history of clonorchiasis (OR: 18.7, p<0.001) were more
      likely to have it. We also found tourists who traveled to China and ate fish
      there (OR: 2.46, p=0.105) or who owned a fish pond (OR: 1.93, p=0.128) were more
      likely to get clonorchiasis. The prevalence of clonorchiasis in Miaoli County was
      relatively low, which can be explained by good sanitation and personal hygiene.
      The Public Health Department of Taiwan should warn Taiwanese travelers about high
      risk areas for contracting clonorchis infection and encourage these travelers to
      avoid going fishing or eating raw fish in high risk areas.

PMID- 24450232
TI  - Taenia infestation in the appendix: a case report.
AB  - Taenia saginata is a zoonotic cestode causing taeniasis. Taeniasis refers to the
      intestinal infection with the adult stage of this tapeworm. An association
      between teaniasis and acute appendicitis is uncommon. We present the case of a 37
      year old male who presented with abdominal pain for one day. He was diagnosed
      with having appendicitis and an appendectomy was performed. Pathology of the
      appendix showed Taenia saginata with eggs in the lumen. Histological analysis
      showed acute inflammation consistent with acute appendicitis caused by T.
      saginata.

PMID- 24450233
TI  - Mosquito species and outdoor breeding places in residential areas in Malaysia.
AB  - We conducted mosquito surveillance at outdoor breeding habitat in 459 households
      at 7 urban locations in Putrajaya, Malaysia from January to December 2010 to
      determine the predominant species and breeding locations. The most common species
      found at all locations was Aedes albopictus. Gardening utensils were the most
      common breeding sites. Of the 1,885 mosquito larvae specimens found, 1,774
      (94.1%) were Ae. albopictus larvae, 84 (4%) were Ae. aegypti larvae and 27 (1%)
      were Culex quinquefasciatus larvae. The Aedes index for each of the locations was
      higher than the goal set by the Ministry of Health for Malaysia. However, the
      container index at each of the locations was within the goal. The Breateau index
      was above the goal set by the Ministry of Health at Precinct 9B1 but the other
      locations were within the goal.

PMID- 24450234
TI  - Effects of grapefruit (Citrus paradisi MACF) (Rutaceae) peel oil against
      developmental stages of Aedes aegypti (Diptera: Culicidae).
AB  - Laboratory bioassay of the essential oil extracted from the grapefruit (Citrus
      paradisi) peel by steam distillation was carried out against the developmental
      stages of the yellow fever vector Aedes aegypti to evaluate its toxicity, and
      ovicidal and larvicidal potency. Volatile oil components isolated and
      characterized by coupled gas chromatography/mass spectrometry included varying
      levels of monoterpene aldehydes, alcohols, and esters. Test results of the
      essential oil showed that egg hatching was completely inhibited at 400 ppm, while
      further development of 1st to 2nd larval stage was inhibited at 100 ppm.
      Regression analysis results also indicated that the peel essential oil
      significantly (p<0.01) reduced the viability of the test eggs and inhibited the
      development of 1st larval stage to 2nd larval instar. The LC50 and LC90 values
      obtained for 2nd instars (180.460, 334.629 ppm, respectively); and for 4th
      instars (210.937, 349.489 ppm, respectively) after 24-hour exposure were time but
      not dose dependent, as each LC value was a product of an inverse relationship
      between the oil concentration and exposure time. The results indicated that the
      peel oil could be a potent persistent larvicide.

PMID- 24450235
TI  - Effect of housing factors on infestation by Aedes aegypti (L.) and Aedes
      albopictus Skuse in urban Hanoi City, Vietnam.
AB  - To determine the effect of housing factors on infestation with Aedes aegypti (L.)
      and Aedes albopictus Skuse we conducted an entomological survey and inspection of
      267 urban houses in Hanoi City, Vietnam. Two hundred ten pupae and 194 adult Ae.
      aegypti were collected from 19 and 88 houses, respectively. One hundred eighty
      one pupae and 24 adult Ae. albopictus were collected from 21 and 14 houses,
      respectively. The presence of a private well was associated with increasing
      infestation with Ae. aegypti adults (p = 0.01) and increased the risk of Ae.
      aegypti and Ae. albopictus pupal presence (p = 0.04 for Ae. aegypti, p = 0.03 for
      Ae. albopictus). The presence of an outdoor space in the household premises was
      associated with a higher risk of Ae. albopictus pupal presence (p = 0.004) and a
      higher risk of high levels of Ae. albopictus adults (p = 0.01); however, it had
      no association with infestation with Ae. aegypti. The presence of an air
      conditioning unit (p = 0.03) and four or more rooms in the residence (p = 0.02)
      were negatively and positively associated with the risk for Ae. albopictus
      presence, respectively.

PMID- 24450236
TI  - Multi-drug resistant gram-negative enteric bacteria isolated from flies at
      Chengdu Airport, China.
AB  - We collected flies from Chengdu Shuangliu International Airport to examine for
      the presence of bacteria and to determine the sensitivity patterns of those
      bacteria. A total of 1,228 flies were collected from 6 sites around Chengdu
      Shuangliu International Airport from April to September 2011. The predominant
      species was Chrysomya megacephala (n=276, 22.5%). Antimicrobial-resistant gram
      negative enteric bacteria (n=48) were isolated from flies using MacConkey agar
      supplemented with cephalothin (20 microg/ml). These were identified as
      Escherichia coli (n=37), Klebsiella pneumoniae (n=6), Pseudomonas aeruginosa
      (n=3) and Aeromonas hydrophila (n=2). All isolated bacteria were tested for
      resistance to 21 commonly used antimicrobials: amoxicillin (100%), ticarcillin
      (100%), cephalothin (100%), cefuroxime (100%), ceftazidime 1 (93.8%),
      piperacillin (93.8%), cefotaxime (89.6%), ticarcillin-clavulanate (81.3%),
      trimethoprim-sulfamethoxazole (62.5%), ciprofloxacin (54.2%), gentamicin (45.8%),
      cefepime (39.6%), tobramycin (39.6%), ceftazidime (22.9%), cefoxitin (16.7%),
      amikacin (16.7%), netilmicin (14.6%), amoxicillin-clavulanate (6.3%) and
      piperacillin-tazobactam (2.1%). No resistance to meropenem or imipenem was
      observed. Antibiotic resistance genes among the isolated bacteria were analyzed
      for by polymerase chain reaction. Thirty of the 48 bacteria with resistance
      (62.5%) possessed the blaTEM gene.

PMID- 24450237
TI  - Compliance with and outcomes of CD4-based national guidelines for prevention of
      mother-to-child transmission of HIV for Thailand, 2006-2007.
AB  - The 2006 Thailand national prevention of mother-to-child transmission of HIV
      (PMTCT) guidelines recommended antiretroviral (ARV) regimen use during antenatal
      care (ANC) be based on CD4 results: highly active antiretroviral therapy (HAART)
      should be used for a CD4 < 200 cells/mm(3) and zidovudine/single-dose nevirapine
      should be used for a CD4 count > or = 200 cell/mm(3). We evaluated compliance
      with and outcomes of these guidelines. We conducted a retrospective chart review
      of HIV-infected women and their infants born during October 2006 - December 2007
      at 27 hospitals in 11 provinces of Thailand. The infant HIV-infection status was
      determined using laboratory test results and death reports. Mother-infant pairs
      were classified as fully, partially, or non-compliant with PMTCT guidelines based
      on CD4 testing history and ARV received. Factors associated with compliance were
      analyzed using univariate and multivariate generalized estimating equations
      (GEE). Among 875 mother-infant pairs reviewed, 387 mothers (44%) had ANC CD4
      testing done, of whom 75 (19%) had a CD4 count < 200 cells/mm(3). Proportions of
      pairs fully, partially and non-compliant with guidelines were 38, 34 and 28%,
      respectively. A definitive infant HIV-infection status was determined in 578
      infants (66%). The overall mother-to-child transmission (MTCT) rate was 5.1% [95%
      confidence interval (95%(CI): 3.8-6.9] and the MTCT rates for the fully,
      partially and non-compliant groups were 1.2% (95% CI: 0.4-3.3), 6.0% (95% CI: 3.7
      9.5) and 9.5% (95% CI: 6.2-14.0; p<0.001). Factors associated with compliance
      were: have ANC, awareness of the mothers' HIV status before delivery, and having
      first ANC prior to 24 weeks gestation. Compliance with the 2006 national PMTCT
      guidelines was low, and the MTCT rates were high among non- and partially
      compliant mother-infant pairs. The simplified PMTCT guidellines introduced in
      2010, might increase compliance with and improve outcomes for Thailand's PMTCT
      program.

PMID- 24450238
TI  - Profile and HIV diagnosis disclosure status of children enrolled in a pediatric
      antiretroviral program in Gauteng Province, South Africa.
AB  - A cross sectional survey was conducted with 121 caregivers of HIV-infected
      children aged 6-13 years enrolled in an antiretroviral treatment (ART) program at
      a tertiary hospital to determine the profile and HIV disclosure status of
      children on ART, as well as the socio-demographic profile of their caregivers.
      The majority of caregivers (n=104, 87.4%) were females, with a mean age of 39.6
      years (range 21-76 years). Eighty-four (70.6%) caregivers had secondary
      education, 61 (51.3%) were single, 83 (69.8%) were unemployed, 73 (61.9%)
      depended on childcare grants, and 51 (42.9%) were biological mothers. The mean
      age of children was 9.4 years (range 1-13 years), 109 (90.8%) were schooling, and
      the mean diagnosis age was 5.2 years. Prevalence of disclosure was 40 (33.3%),
      mean disclosure age was 9.4 years (range 3-13 years), and mean diagnosis age was
      5.2 years. Fifteen (37.5%) of the children were told their HIV diagnosis by
      biological mothers, 10 (25%) by healthcare providers, 7 (17.5%) by grandmothers,
      and 8 (20%) were told by other relatives and foster parents. The prevalence of
      diagnosis disclosure to HIV infected children was higher than previously reported
      rates in South Africa and could be attributed to the older mean age of diagnosis.
      Although biological mothers were the main caregivers, they disclosed the HIV
      diagnosis to only one-third of the children. There is a need for more research to
      profile HIV infected children accessing ART in public health facilities to inform
      interventions to manage this growing population of children.

PMID- 24450239
TI  - Clinical profile of patients diagnosed with leptospirosis after a typhoon: a
      multicenter study.
AB  - This study described the clinical features and complications of leptospirosis
      among patients seen at nine tertiary hospitals from September 28 to November 30,
      2009 after a heavy rainfall typhoon. The clinical findings of the confirmed cases
      were compared with the previous clinical studies on seasonal leptospirosis in the
      Philippines. Risk factors for complicated disease were also identified. Confirmed
      cases were based on any of the following: positive leptospiral cultures of blood
      or urine, single high leptospira microscopic agglutination test (MAT) titer of
      1:1,600, a fourfold rise in MAT, and/or seroconversion. Of 670 patients with
      possible leptospirosis, 591 were probable by the WHO criteria, 259 (44%) were
      confirmed. Diagnosis was confirmed by MAT 176 (68%), by culture 57 (22%), and by
      MAT and culture 26 (10%). The mean age of the confirmed cases was 38.9 years (SD
      14.3). The majority were males (82%) and had a history of wading in floodwaters
      (98%). The majority of the patients presented with nonspecific signs, with fever
      as the most common (98.5%). Other findings were myalgia (78.1%), malaise (74.9%),
      conjunctival suffusion (59.3%), oliguria (56.6%), diarrhea (39%), and jaundice
      (38%). Most of the patients presented with a moderate-to-severe form of
      leptospirosis (83%). Complications identified were renal failure (82%), pulmonary
      hemorrhage (8%), meningitis (5%), and myocarditis (4%). Mortality rate was 5%,
      mostly due to pulmonary hemorrhage. This study emphasizes the importance of
      public awareness and high index of suspicion among clinicians of leptospirosis
      during the monsoon months when flooding is common. Early recognition and
      detection of the disease should decrease morbidity and mortality.

PMID- 24450240
TI  - Causative agents of nosocomial bloodstream infections and their antimicrobial
      susceptibility patterns.
AB  - The aim of this study was to retrospectively investigate nosocomial bloodstream
      infections (NBI) and their antimicrobial susceptibility patterns at Afyon
      Kocatepe University (AKU) Hospital, Turkey, from January 2006 to December 2011
      and to determine the risk factors for nosocomial BSI. Subjects were aged > or =
      18 years. The data were obtained from patient files. Five hundred seventy-nine
      nosocomial infections in 461 patients were included in the study. Eighty-four
      point six percent was primary and 15.4% were secondary infections. Gram-positive
      cocci were the most common organisms. When compared year by year there was an
      increasing trend in antibacterial resistant gram-negative bacilli. The most
      common infection risk factors were H2 histamine receptor blocker use and blood
      transfusions. Regular surveillance of BSI is important to monitor changes in the
      types of microorganisms and their resistance patterns.

PMID- 24450241
TI  - Cryptococcal infection of the vocal folds.
AB  - Cryptococcosis of the larynx is rare. In this manuscript we present a case of
      laryngeal cryptococcosis with a clear history of pigeon exposure. Cryptococcal
      laryngitis may present as hoarseness without other typical symptoms, even in
      immunocompetent individuals.

PMID- 24450242
TI  - Awareness of and factors influencing willingness to receive a tetanus-diphtheria
      toxoid booster vaccine among Thai adults.
AB  - Adults who complete the diphtheria tetanus pertussis (DTP) vaccine series during
      childhood should receive a tetanus-diphtheria toxoid (Td) booster vaccine every
      10 years. We studied awareness of and willingness to receive the Td booster
      vaccine as well as factors influencing these attitudes. A total of 1,284
      participants were interviewed using a questionnaire at the out-patient department
      (OPD) of Siriraj Hospital, Bangkok, Thailand from January 31 to February 28,
      2011. The sample population included: OPD patients, family members accompanying
      patients and medical personnel other than doctors. Seven percent of the 961
      general participants and 26.3% of the 320 medical personnel who completed the
      questionnaire were aware of the need to receive the Td booster vaccine. Eighty
      six point five percent of participants stated they be willing to receive the
      vaccine if they were instructed by their doctors. Logistic regression analyses
      showed the following factors correlated with awareness of the need to receive the
      vaccine: born after 1978 (aOR = 2.17; 95% CI: 1.59-2.97), higher income (aOR =
      1.93; 95% CI: 1.37-2.72), and higher general preventive awareness score (aOR =
      1.08; 95% CI: 1.02-1.14). Factors that correlated with willingness to receive the
      vaccine were: higher education (aOR = 2.17; 95% CI: 1.54-3.05), a higher score on
      general knowledge of tetanus-diphtheria (aOR = 2.00; 95% CI: 1.15-3.51), a higher
      general preventive awareness score (aOR = 1.06; 95% CI: 1.007-1.115), and
      previous experience with the Td booster vaccine (aOR = 2.85; 95% CI: 1.71-4.76),
      Under-awareness of the adult vaccination program remains a problem in Thailand
      especially among older generations and low-socioeconomic groups. As passive
      immunity wanes with time, public health authorities need to take action to
      educate the general population and health care workers about the importance of
      the Td booster vaccine.

PMID- 24450243
TI  - Genotyping of beta thalassemia trait by high-resolution DNA melting analysis.
AB  - Beta thalassemia is a common hereditary hemalogogical disease in Thailand, with a
      prevalence of 5-8%. In this study, we evaluated the high resolution DNA melting
      (HRM) assay to identify beta thalassemia mutation in samples from 143 carriers of
      the beta thalassemia traits in at risk couples. The DNA was isolated from venous
      blood samples and tested for mutation under a series of 5 PCR-HRM (A, B, C, D and
      E primers) protocols. The A primers were for detection of beta thalassemia
      mutations in the HBB promoter region, the B primers for mutations in exon I, the
      C primers for exon II, the D primers for exon III and the E primers for the 3.4
      kb deletion mutation. The mutations were diagnosed by comparing the complete
      melting curve profiles of a wild type control with those for each mutant sample.
      With the PCR-HRM technique, fourteen types of beta thalassemia mutations were
      detected. Each mutation had a unique and specific melting profile. The mutations
      included 36.4% (52 cases) codon 41/42-CTTT, 26.6% (38 cases) codon 17 A-T, 11.2%
      (16 cases) IVS1-1 G-T, 8.4% (12 cases) codon 71/72 +A, 8.4% (12 cases) of the 3.4
      kb deletion and 3.5% (5 cases) -28 A-G. The remainder included one instance each
      of -87 C-A, -31 A-C, codon 27/28 +C, codon 30 G-A, IVS1-5 G-C, codon 35 C-A,
      codon 41-C and IVSII -654 C-T. Of the total cases, 85.8% of the mutations could
      be detected by primers B and C. The PCR-HRM method provides a rapid, simple and
      highly feasible strategy for mutation screening of beta thalassemia traits.

PMID- 24450244
TI  - Cost-benefit analysis of the probiotic treatment of children hospitalized for
      acute diarrhea in Bangkok, Thailand.
AB  - We studied the cost-benefit of using probiotics (Lactobacillus acidophilus and
      Bifidobacterium bifidum) in the treatment of 106 children hospitalized with acute
      diarrhea using a double-blind randomized, placebo-controlled trial. The median
      length of hospital stay was significantly shorter in the probiotics group than in
      the controlled group (2 versus 3 days, p=0.049), but the median duration of
      diarrhea and direct medical costs were not significantly different (4 versus 5
      days, p=0.068 and 4,418.75 versus 4,778.75 Thai Baht, p=0.342). Taking into
      consideration parental income loss, a non-significant lower expense was seen in
      the probiotics group (6,800.33 versus 7,970.92 Thai Baht, p=0.177). A greater
      cost-benefit with the probiotic treatment is probable, but was not statistically
      significant in this small study. In conclusion, the probiotics tested shortened
      the duration of hospitalization of children with diarrhea but the total expenses
      were not different.

PMID- 24450245
TI  - Iodine status after iodized salt supplementation in schoolchildren of eastern
      Nepal.
AB  - This study was designed to assess the urinary iodine concentrations of
      schoolchildren at baseline and after iodized salt supplementation in eastern
      region of Nepal. A cross sectional study was conducted from August 2009 to July
      2011 among schoolchildren of three eastern districts of Nepal: Sunsari, Dhankuta,
      and Tehrathum. A sample of 828 school age children from the three districts was
      chosen for the study after obtaining written consent from their guardians. The
      schoolchildren treatment group (n=300) was provided with a supplement of iodized
      salt for six months. Urinary iodine concentration was estimated by ammonium
      persulfate digestion microplate method at baseline and after supplementation.
      Urinary iodine controls L1, L2 (Seronorm, Norway) were analyzed to obtain intra
      assay CVs (L1 = 7.4%, L2 = 3.3%) and inter assay CVs (L1=23.5%, L2=11.26%).
      Median interquartile range urinary iodine concentration in the three districts:
      Sunsari, Dhankuta and Tehrathum at baseline versus intervention were 272.0 (131.5
      473.0) microg/l versus 294.0 (265.0-304.0) microg/l (p=0.379), 247.0 (144.5
      332.32) versus 361.0 (225.66-456.52) microg/l (p<0.001), and 349.5 (203.75
      458.09) microg/l versus 268.76 (165.30-331.67) microg/l (p<0.001), respectively.
      This study indicated improved iodine status and increased median urinary iodine
      concentration after iodized salt supplementation. Regular monitoring of
      population urinary iodine concentration at national and regional levels should be
      performed to ensure that all individuals have optimal delivery of iodine
      nutrition.

PMID- 24450246
TI  - Blood lead levels among rural Thai children exposed to lead-acid batteries from
      solar energy conversion systems.
AB  - We evaluate blood lead levels among Thai children to determine if exposure to
      lead-acid batteries is associated with elevated blood lead levels (EBLL). We
      screened 254 children aged 1-14 years old from 2 rural Thai villages for blood
      lead levels. We also screened 18 of 92 houses in these 2 villages for the
      presence of environmental lead. The overall prevalence of EBLL (> or = 10
      microg/dl) was 43.3% and the mean lead level among study subjects was 9.8 +/- 5.1
      microg/dl. The blood lead levels significantly decreased with increasing age.
      Fifty point eight percent of children who lived in a house with vented lead-acid
      batteries had EBLL while 23.3% of children who lived in a house without vented
      lead-acid batteries had EBLL. Multiple logistic regression analysis revealed a
      significant positive association between the presence of vented lead-acid
      batteries and EBLL, after adjusting for other variables. Forty-two point nine
      percent of house floor dust samples collected near the batteries had elevated
      lead levels, 7.1% of house floor dust samples collected from other areas in the
      house had elevated lead levels and 0% of the house floor dust samples collected
      in houses without vented lead-acid batteries had elevated lead levels. In the
      sampled houses with vented lead-acid batteries, lead contamination was found in
      the drinking-water kept in household containers, but not in the tap water or
      other village sources of water. Improper care and placement of vented lead-acid
      batteries can result in lead contamination in the home environment causing EBLL
      in exposed children.

PMID- 24450247
TI  - Residues of organophosphate pesticides used in vegetable cultivation in ambient
      air, surface water and soil in Bueng Niam Subdistrict, Khon Kaen, Thailand.
AB  - Agricultural pesticide utilization is one of the important problems in rural and
      urban crop-cultivated areas, with the majority of pollutants dispersing via
      ambient air, water and other natural pathways. This study was therefore conducted
      in a specially selected village which is known to be a leading vegetable growing
      area in Khon Kaen Province. The aim of the study was to assess pesticide
      residues, and measure the seasonal fluctuations in organophosphate concentrations
      during 2010 in the environment of a risk area. Samples from selected sites were
      collected in two phases: Phase I was in summer (during March to May) and Phase II
      was in winter (during October to December). A total of 150 samples were analyzed
      using gas chromatography with flame photometric detection. The results showed
      that dicrotophos, chlorpyrifos, profenofos and ethion were found at the highest
      concentrations in soil and at the lowest concentrations in ambient air (p<0.001).
      The highest mean concentration of a pesticide in ambient air samples was 0.2580
      +/- 0.2686 mg/m(3) for chlorpyrifos in summer and 0.1003 +/- 0.0449 mg/m(3) for
      chlorpyrifos in winter. In surface water samples, the highest mean concentration
      of a pesticide was 1.3757 +/- 0.5014 mg/l for dicrotophos in summer and 0.3629 +/
      0.4338 mg/l for ethion in winter. The highest mean concentration of a pesticide
      in soil samples was 42.2893 +/- 39.0711 mg/kg ethion in summer and 90.0000 +/-
      24.1644 mg/kg of ethion in winter.

PMID- 24450248
TI  - Factors associated with higher levels of depressive symptoms among international
      university students in the Philippines.
AB  - Over the years, the number of international university students has been
      increasing in the Philippines. Depression tends to be common among this
      demographic sector, because of the varying challenges and expectations associated
      with studying abroad. Depression can be prevented if its symptoms, particularly
      those at higher levels, are identified and addressed early and effectively. This
      survey examined the social and demographic factors that are significantly
      associated with higher levels of depressive symptoms. One hundred twenty-six
      international university students were interviewed using the University Students
      Depression Inventory. Of the 13 factors analyzed, 3 were found with statistically
      significant associations with more intense levels of depressive symptoms. These
      factors were: level of satisfaction with one's financial condition, level of
      closeness with parents, and level of closeness with peers. In identifying
      international students with greater risk for depression, characteristics related
      to their financial condition and primary group relationships can be considered.
      There is a need to carry out more studies to confirm this initial evidence. The
      findings can help guide further discourse, research and program to benefit
      international students with higher levels of depressive symptoms.

PMID- 24450249
TI  - Oral health status and oral hygiene habits among children aged 12-13 years in
      Yangon, Myanmar.
AB  - We conducted a cross sectional study among children aged 12-13 years in Yongon,
      Myanmar to assess the oral health status and oral hygiene habits. The studied 220
      students were from two high schools, one urban and the other rural. We conducted
      an oral health examination following WHO criteria and used a self-administrated
      questionnaire. The prevalence rate of dental caries among the study population
      was 53.2%. The mean number of decayed, missing and filled teeth (DMFT) was 1.7 +/
      2.1 teeth per person (decayed, 1.5 +/- 1.9); missing 0.0 +/- 0.2; filled, 0.1 +/
      0.4). Multivariate analysis revealed significant risk factors for dental caries
      were: the geographical location of the school (adjusted OR=2.24; 95% CI: 1.01
      4.94), occupational status of the father (adjusted OR=2.83; 95% CI: 1.05-7.62)
      and the child's attitude about dental caries (adjusted OR=2.35; 95% CI: 1.18
      4.67). Knowledge and oral hygiene habits were not associated with dental caries.
      The results of this study suggest the need to change from restoration orientated
      dentistry to dental public health care services, to reduce of the high level of
      dental caries in this age group.

PMID- 24450250
TI  - Epidemiological and clinical features of erythema infectiosum in children in Novi
      Sad from 2000 to 2009.
AB  - BACKGROUND/AIM: Erythema infectiosum (EI) is a common childhood illness, caused
      by human parvovirus B19. It occurs sporadically or in epidemics and is
      characterized by mild constitutional symptoms and a blotchy or maculopapular lacy
      rash on the cheeks (slapped-cheek) spreading primarily to the extremities and
      trunk. The aim of our study was to analyse the epidemiological and clinical
      characteristics of erythema infectiosum in children. METHODS: This study included
      88 children observed in the Department of Dermatology of the Institute for Child
      and Youth Health Care of Vojvodina, in Novi Sad, during the period January 2000
      December 2009. We compared the data about the clinical characteristics during and
      after the outbreak of EI observed from December 2001 to September 2002. The data
      were retrieved from the hospital database. RESULTS: During the study period, EI
      was detected in 88 children (44 females and 44 males), 0.213% of the total number
      of 41,345 children observed in the Department of Dermatology. An outbreak of
      erythema infectiosum was observed from December 2001 to September 2002, with the
      peak frequency in April and May 2002 and 39 diagnosed cases, and stable number of
      cases from 2005 to 2009 (a total of 49 diagnosed cases). The average age of
      infected children was 7.59 +/- 3.339. Eleven (12.5%) children were referred from
      primary care pediatricians with the diagnosis of urticaria or rash of allergic
      origin. The most constant clinical sign was reticular exanthema on the limbs,
      present in 100% of the cases, followed by 89.77% of cheek erythema. Pruritus was
      present in 9.09% of the children, mild constitutional symptoms in 5.68% and
      palpable lymph glands in 3.41% of the children. In all the cases the course of
      the disease was without complications. CONCLUSION: The results of this study
      confirm the presence of EI (the fifth disease) in our area with a mild course in
      the majority of patients. Since the diagnosis of EI is usually based on clinical
      findings, continuing medical education of primary health care pediatricians is
      essential for reducing the number of misdiagnosed cases.

PMID- 24450251
TI  - Histomorphological and clinical study of primary and secondary glomerulopathies
      in Southeast Serbia (20-year period of analysis).
AB  - BACKGROUND/AIM: Epidemiological studies of renal biopsies have been performed to
      follow up the incidence of glomerular diseases on a specified territory and to
      compare the obtained results with results from other regions. The aim of this
      study was to analyze the frequency of certain histopathophysiological types of
      glomerular diseases on the territory of Southeast Serbia. METHODS: In a 20-year
      period (1986-2006), 316 kidney biopsies were performed in patients with clinical
      signs of impaired renal function, in Southeast Serbia. On average 1.6 biopsies
      were made per year per 100 000 inhabitants. RESULTS: Biopsies of adult patients
      represented 88% of all biopsies, biopsies in children (aged under 18 years)
      represented 8%, while biopsies of elderly patients (more than 60 years)
      represented 4% of all biopsies. The predominance of male patients was described
      with male/female ratio of 1.4. The most frequent clinical manifestation in
      patients at the time of biopsy were nephrotic syndrome (42.5%), and asymptomatic
      proteinuria and/or hemamuria (31.3%) and nephritic syndrome (14.9%). The most
      common glomerular disease was IgA nephropathy with an incidence of 21.5% of total
      biopsy diagnosed glomerulopathies, followed by: membranous glomerulonephritis
      (12.6%), focal segmental proliferative and sclerosing glomerulonephritis (10.7%),
      lupus nephritis (8.4%), nephroangiosclerosis (7.0%), mesangio-proliferative
      glomerulonephritis (6.1%), minimal change disease (2.8%), mesangiocapillary
      glomerulonephritis (2.3%). CONCLUSION: The frequency of certain histopathologic
      findings significantly correlated with data from studies that we used for
      comparison, with the exception of minimal change disease whose incidence in our
      study was smaller.

PMID- 24450252
TI  - Does the addition of Serenoa repens to tamsulosin improve its therapeutical
      efficacy in benign prostatic hyperplasia?
AB  - BACKGROUND/AIM: It has been observed that a large number of patients with low
      urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH)) has been
      treated with a combination of tamsulosin (TAM) + Serenoa repens (SR) (TAM + SR).
      The aim of this study was to compare a combination TAM + SR with TAM and SR
      alone, to see if there was any difference in efficacy and tolerance of each in
      patients with LUTS/BPH. METHODS: In this prospective study patients had to have
      prostate volume (PV) < 50 mL, International Prostate Symptom Score (IPSS) of 7
      18, Quality of Life score (QoLs) > 3, a maximal flow rate (Qmax) of 5-15 mL/s,
      with post voiding residual volume (PVR) < 150 mL and serum prostatic antigen
      (PSA) < 4 ng/mL. TAM (0.4 mg) was administered once a day, SR (320 mg) daily or
      SR (320 mg) + TAM (0.4 mg) daily for a median period of 6 months. RESULTS: A
      total of 297 patients were recruited, whereas 265 patients were fully available:
      87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There
      was no statistically significant difference between the treatment groups in the
      sense of demographic and other baseline parameters. No difference was found among
      the 3 treatment groups, neither in the major endpoint of the study in the sense
      of a change between baseline and final evaluation in total IPSS, obstructive and
      irritative subscores, improvement of QoLs, increase in Qmax, nor for the second
      endpoint including diminution of PV, PSA and PVR. During the treatment period 20
      (23%) of the patients managed with TAM and 17 (21%) with TAM + SR had drug-
      treated with related adverse reactions. No adverse effect was detected in the
      group SR. CONCLUSION: Treatment of BPH by both SR and TAM seems to be efficacious
      alone. None of them had superiority over another and, additionally, a combined
      therapy (TAM + SR) does not provide extra benefits. Furthermore, SR is a well
      tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

PMID- 24450253
TI  - Risk factors for epithelial ovarian cancer in the female population of Belgrade,
      Serbia: a case-control study.
AB  - BACKGROUND/AIM: Ovarian cancer (OC) comprises 3% of all cancers, but it is the
      fifth most common cause of cancer death in women. The aim of this case-control
      study was to determine the risk factors for OC in the female population of
      Belgrade, Serbia. METHODS: A total of 80 consecutive patients were enrolled in
      the study between 2006 and 2008 in two national referral centers for OC in
      Serbia. The control subjects were recruited during the regular gynecological
      check-ups in the Public Health Center of the corresponding municipalities. All
      the study participants were interviewed during their visits to the above
      mentioned institutions by two physicians using the same questionnaire. In order
      to analyze the influence of specific exposure to the risk of the disease, we
      categorized variables according to the cut-off values. Odds ratios (OR) and 95%
      confidence intervals (95% CI) were calculated separately for each variable using
      univariate conditional logistic regression analysis. RESULTS: There were no
      statistically significant differences in educational level, years of schooling,
      occupational and employment status between patients with OC and women in the
      control group. Oral contraceptives use and other contraceptive methods (condoms,
      mechanical contraceptive devices) were highly statistically significantly more
      frequent among women in the control group (OR = 0.2, 95% CI 0.1-0.7, p = 0.005;
      OR = 0.1, 95% CI 0.01-0.5, p = 0.001, respectively). The patients with OC
      practiced sports for 6.3 +/- 2.1 years, and controls for 11.8 +/- 9.9 years.
      Sport and recreation activities were statistically significantly protective (OR =
      0.2, p = 0.011; OR = 0.4, p = 0.019). Tea consumption on daily basis had a highly
      statistically significat protective effect (OR = 0.3, p = 0.001). CONCLUSIONS:
      Oral contraceptives use and physical activity were independent protective factors
      for OC in this study.

PMID- 24450254
TI  - Association between aortic stenosis severity and contractile reserve measured by
      two-dimensional strain under low-dose dobutamine testing.
AB  - BACKGROUND/AIM: Early detection of left ventricle (LV) systolic dysfunction could
      be a clue for surgical treatment in patients with significant aortic stenosis
      (AS). Therefore, we evaluated LV peak of global longitudinal strain (PGLS) using
      speckle tracking imaging at rest and during low-dose dobutamine infusion in
      asymptomatic patients with moderate and severe AS and preserved LV ejection
      fraction (EF). METHODS: All the patients underwent coronary angiography and had
      no obstructive coronary disease (defined as having no stenosis greater than 50%
      in diameter). The patients were divided into two groups: above and below median
      of 0.785 cm2 aortic valve area (AVA). PGLS was measured from acquired apical 4
      chamber and 2-chamber cine loops using a EchoPac PC-workstation at rest and
      during 5 microg/kg/min, 10 microg/kg/min, and 20 microg/kg/min dobutamine
      infusion, respectively. The global strain was the average of segment strains from
      the apical views. RESULTS: A total of 62 patients with moderate and severe AS
      (AVA < = 1.5 cm2), the mean age 66.12 +/- 9.91, (57.14% males), were enrolled in
      this prospective study. At rest, mean gradient was 43.57 +/- 0.29 mmHg and mean
      EF was 72.24 +/- 0.45%. When divided according to median AVA, both groups had
      decreased average PGLS at rest (-9.33 +/- 4.46% vs -8.95 +/- 3.08%; p = ns).
      During dobutamine both groups increased their average PGLS, but only the group
      with AVA > median reached the statistical significance (- 8.71 +/- 2.68% vs 
      11.93 +/- 3.74%, p = 0.002). In addition, PGLS increase was also significant in 4
      chamber view in the patients with AVA above median, but only when comparing
      baseline to peak 20 microg/kg/min (-10.72 +/- 3.07% vs -13.14 +/- 4.79%; p =
      0.034). Conversely, in both groups the increase of PGLS in 2-chamber view did not
      reach significance. CONCLUSION: Two-dimensional strain speckle tracking analysis
      of myocardial deformation with measurement of peak systolic strain during
      dobutamine infusion is a feasible and accurate method to determine myocardial
      longitudinal systolic function and contractile reserve and may contribute to
      clinical decision making in patients with significant AS.

PMID- 24450255
TI  - Risk factors for vancomycin-resistant Enterococcus colonization in hematologic
      patients.
AB  - BACKGROUND/AIM: Vancomycin-resistant Enterococci (VRE) is one of the most
      important hospital pathogens. The aim of the study was to evaluate VRE
      colonization in patients hospitalized at the Hematology Intensive Care Unit, as
      well as the associated risk factors. METHODS: A prospective cohort study involved
      70 patients hospitalized at the Intensive Care Unit (ICU), Clinic for Hematology,
      Clinical Center of Serbia, Belgrade, during 3 months. Baseline demographic data,
      data about antibiotic usage and other risk factors for VRE colonization during
      the present and previous hospitalizations (within 6 months) were recorded for
      each patient using the questionnaire. Feces or rectal swab was collected for
      culture from patients on admission and at discharge in case when VRE was not
      isolated on admission. Enterococci were isolated by standard microbiological
      methods. Isolate sensitivity was tested by disk-diffusion test using 30 microg/mL
      (BBL) Vancomycin plates according to the Clinical and Laboratory Standards
      Institute (CLSI) standard. RESULTS: Analysing results showed that 7% of the
      patients had been already colonized with VRE upon ICU admission. The rate of VRE
      colonization during present hospitalization was 41.5%. Univariate logistic
      regression demonstrated the statistically significant differences in diagnosis,
      length of present stay, use of aminoglycosides and piperacillin/tazobactam in
      present hospitalization, duration of use of carbapenem and
      piperacillin/tazobactam in present hospitalization between the VRE-colonized and
      non-colonized patients. Acute myeloid leukemia (AML), use of carbapenem in
      previous hospitalization and duration of use of piperacillin/tazobactam in
      present hospitalization were independent risk factors for VRE-colonized patients
      according to multivariate logistic regression. CONCLUSION: VRE colonization rate
      was high among the patients admitted to hematology ICU. Rational use of
      antibiotics and active surveillance may be helpful preventive measures against
      the development of bacterial resistance to antimicrobial agents.

PMID- 24450256
TI  - Assessing the quality of angiographic display of brain blood vessels aneurysms
      compared to intraoperative state.
AB  - BACKGROUND/AIM: Aneurysms in brain blood vessels are expanding bags composed of a
      neck, body and fundus. Clear visibility of the neck, the position of the aneurysm
      and surrounding structures are necessary for a proper choice of methods for
      excluding the aneurysm from the circulation. The aim of this study was to
      evaluate the reliability of spatial reconstruction of blood vessels of the brain
      based on the original software for 3D reconstruction of the equipment
      manufacturer and a personal computer model developed earlier in the Clinic for
      Neurosurgery, Clinical Center of Serbia, Belgrade, compared to intraoperative
      identification of these aneurysms. METHODS: This study included 137 patients of
      both sexes. The presence of an aneurysm was verified by angiographic methods
      [computed tomographic angiography (CTA), multislice computed tomography
      angiography (MSCTA), magnetic resonance imaging angiography (MRA), or digital
      subtraction angiography (DSA)]. RESULTS: The quality score (0 to 5) for CTA was
      3.180 +/- 0.961, MSCTA 4.062 +/- 0.928, and for DSA 4.588 +/- 0.758 (p < 0.01).
      The results of this study favorite conventional angiography as the gold standard
      for diagnostic of intracranial aneurysms. CONCLUSION: The results of this study
      are consistent with current publications review and clearly recognize the
      advantages and disadvantages of diagnostic neuroradiological procedures, with DSA
      of brain blood vessels as a binding preoperative diagnostic procedure in cases in
      who it is not possible to clearly visualize the supporting blood vessel and neck
      of the aneurysm by using the findings of CTA, MRA and MSCTA.

PMID- 24450257
TI  - Surgical anatomy and histology of the levator palpebrae superioris muscle for
      blepharoptosis correction.
AB  - BACKGROUND/AIM: The detailed knowledge of the architecture of the upper eyelid is
      very important in numerous upper eyelid corrective surgeries. The article deals
      with the detailed anatomy of the major components of the upper lid, which are
      commonly seen in surgical practice. METHODS: This study was conducted on 19 human
      cadavers (12 adults and 7 infants) without pathologic changes in the orbital
      region and eyelids. Anatomic microdissection of the contents of the orbita was
      performed bilaterally on 12 orbits from 6 unfixed cadavers (3 male and 3 female).
      Micromorphologic investigations of the orbital tissue were performed on 8 en bloc
      excised and formalin-fixed orbits of infant cadavers. Specimens were fixed
      according to the Duvernoy method. An intra-arterial injection of 5% mixture of
      melt formalin and black ink was administered into the carotid arterial system.
      Using routine fixation, decalcination, dehydration, illumination, impregnation
      and molding procedures in paraplast, specimens were prepared for cross-sections.
      RESULTS: The measurement of the muscle length and diameter in situ in 6 nonfixed
      cadavers (12 orbits) showed an average length of the levator palpbrae superioris
      (LPS) muscle body of the 42.0 +/- 1.41 mm on the right, and 40.3 +/- 1.63 mm on
      the left side. In all the cases, the LPS had blood supply from 4 different
      arterial systems: the lacrimal, supratrochlear, and supraorbital artery and
      muscle branches of the ophthalmic artery. The LPS muscle in all the specimens was
      supplied by the superior medial branch of the oculomotor nerve. The connective
      tissue associated with the LPS muscle contains two transverse ligaments: the
      superior (Whitnall's) and intermuscular transverse ligaments (ITL). The orbital
      septum in all the specimens originated from the arcus marginalis of the frontal
      bone, and consisted of two layers--the superficial and the inner layer. In
      addition, a detailed histological analysis revealed that the upper eyelid's
      crease was formed by the conjoined fascia including the fascia of the orbicularis
      muscle, the superficial layer of the orbital septum, and the aponeurosis of the
      LPS muscle, as well as the pretarsal fascia. CONCLUSION: The conducted study
      provided a valuable morphological basis for biomechanical and clinical
      considerations regarding blepharoptosis surgery.

PMID- 24450258
TI  - High thoracic epidural anesthesia in patients with synchronous carotid
      endarterectomy and off-pump coronary artery revascularization.
AB  - BACKGROUND/AIM: In order to reduce the risk of cerebrovascular insults (CVI), the
      latest recommendations suggest that carotid endarterectomy (CEA) is strongly
      indicated in patients scheduled for coronary surgery when significant carotid
      artery stenosis is symptomatic and/or bilateral. The best results are obtained in
      small studies with CEA performed immediately prior to off-pump coronary bypass
      (OPCAB). We present 16 consecutive patients who underwent synchronous CEA and
      OPCAB under general anesthesia combined with high thoracic epidural anesthesia
      (TEA) in order to evaluate the safety and potential benefits of such anesthetic
      management. METHODS: A total of 16 consecutive patients scheduled for
      simultaneous CEA and OPCAB with no contraindication for TEA were enrolled in the
      study. All the patients were anesthetized with TEA combined with general
      anesthesia. Early extubation was planed in all the patients for early assessment
      of neurological outcome. Demographics, comorbidity, quality of postoperative
      recovery, duration of mechanical ventilation, successful early extubation,
      outcome, length of Intensive Care Unit (ICU) and hospital stay were recorded.
      RESULTS: Only two patients did not fulfill the criteria for early extubation. The
      average duration of mechanical ventilation for patients who fulfilled criteria
      for early extubation was 87.9 +/- 85.0 (0-255) min. Five (31.25%) patients were
      extubated in the operating theater at the end of surgery. There were no deaths,
      nor neurological complications of TEA. Seven (43.7%) patients had at least one of
      the postoperative complications considered significant. None of them had CVI.
      None of the early extubated patients was reintubated or had postoperative
      respiratory failure. CONCLUSION: Our study revealed that a combination of general
      anesthesia with TEA appears to be good choice in synchronous CEA and OPCAB due to
      advantages of early extubation and early neurological assessment. Larger studies
      are necessary to determine real benefits on both short and long-term outcomes of
      such anesthetic management in synchronous CEA and OPCAB.

PMID- 24450259
TI  - Psychological problems in patients with type 2 diabetes--clinical considerations.

PMID- 24450260
TI  - Cardiovascular effects of resveratrol.

PMID- 24450261
TI  - Two cases of uveitis masquerade syndrome caused by bilateral intraocular large B
      cell lymphoma.
AB  - INTRODUCTION: Sometimes it is not easy to clinically recognize subtle differences
      between intraocular lymphoma and noninfectious uveitis. The most common lymphoma
      subtype involving the eye is B-cell lymphoma. CASE REPORT: We presented two
      patients aged 59 and 58 years with infiltration of the subretinal space with a
      large B-cell non-Hodgkin intraocular lymphoma. The patients originally had
      clinically masked syndrome in the form of intermediate uveitis. As it was a
      corticosteroid-resistant uveitis, we focused on the possible diagnosis of
      neoplastic causes of this syndrome. During hospitalization, the neurological
      symptoms emerged and multiple subretinal changes accompanied by yellowish white
      patches of retinal pigment epithelium with signs of vitritis, which made us
      suspect the intraocular lymphoma. Endocranial magnetic resonance imaging
      established tumorous infiltration in the region of the left hemisphere of the
      cerebellum. The histopathological finding confirmed the diagnosis of large B-cell
      non-Hodgkin lymphoma of risk moderate degree, immunoblast--centroblast
      cytological type. The other patient had clinical chronic uveitis accompanied by
      yellowish shaped white echographic changes of the retina and localized changes in
      the level of the subretina. The diagnosis of lymphoma was made by brain biopsy.
      CONCLUSION: Uveitis masquerade syndrome should be considered in all patients over
      40 years with idiopathic steroid-resistant uveitis. Treatment begun on time can
      affect the course and improve the prognosis of uveitis masquerade syndrome (UMS)
      and systemic disease.

PMID- 24450262
TI  - Stromal reaction and prognosis in acinic cell carcinoma of the salivary gland.
AB  - INTRODUCTION: Primary acinic cell carcinoma (ACC) is an uncommon malignant
      neoplasm of the salivary gland (SG), which usually presents as slow growing
      tumor. CASE REPORT: We reported a 69-year-old woman with tumor in the right
      parotid gland with a 5-year progress. Biopsy sections revealed a hybrid form of
      ACC with a low- and high-grade component and prominent lymphoid tissue in tumor
      stroma. Immunohistochemistry was performed to define the molecular profile of
      this unusual ACC, with special interest for stromal influence on to the
      proliferative activity of ACC with dedifferentiation. We detected that the level
      and the type of stromal lymphoid reaction (particularly CD8+/CD4+ ratio) had a
      significant influence on to Ki-67 index in the high-grade component of ACC, as
      well as the involvement of the CXCR4 signaling axis in the stromal reaction
      influence. CONCLUSION: We suggest that tumor stroma may be a source of potential
      new tumor biomarkers which can determine the aggressivity of this tumor.

PMID- 24450263
TI  - Multisystem Langerhans cell histiocytosis coexisting with metastasizing
      adenocarcinoma of the lung: a case report.
AB  - INTRODUCTION: Langerhans cell histiocytosis (LCH) is an uncommon disease of
      unknown etiology characterized by uncontrolled proliferation and infiltration of
      various organs by Langerhans cells. CASE REPORT: We presented a 54-year-old man,
      heavy smoker, with dyspnea, cough, hemoptysis, headache and ataxia, who died
      shortly after admission to our hospital. On the autopsy, tumor was found in the
      posterior segment of the right upper pulmonary lobe as well as a right-sided
      occipitoparietal lesion which penetrated into the right ventricle resulting in
      internal and external hematocephalus. Histologically and immunohistohemically,
      the diagnosis of primary lung adenocarcinoma with brain metastasis was made
      (tumor cells showed positivity for CK7 and TTF-1 which confirmed the diagnosis).
      In the lung parenchyma around the tumor, as well as in brain tissue around the
      metastatic adenocarcinoma histiocytic lesions were found. Light microscopic
      examination of the other organs also showed histiocytic lesions involving the
      pituitary gland, hypothalamus, spleen and mediastinal lymph nodes.
      Immunohistochemical studies revealed CD68, S-100 and CD1a immunoreactivity within
      the histiocytes upon which the diagnosis of Langerhans' cells histiocytosis was
      made. CONCLUSION: The multisystem form of LCH with extensive organ involvement
      was an incidental finding, while metastatic lung adenocarcinoma to the brain that
      led to hematocephalus was the cause of death.

PMID- 24450264
TI  - Successful implantation of a biventricular pacing and defibrillator device via a
      persistent left superior vena cava.
AB  - INTRODUCTION: Persistent left superior vena cava is the most common thoracic
      venous abnormality which is usually asymptomatic, found incidentally during
      pacemaker implantation. The main problem is related to reaching the appropriate
      pacing site and ensuring stable lead placement. CASE REPORT: We reported a
      successful implantation of a biventricular pacing and defibrillator device (CRT
      D) via a persistent left superior vena cava in a 55-year-old man with dilated
      cardiomyopathy and severe heart failure. A persistent left superior vena cava was
      detected during CRT-D implantation. We managed to position electrodes in the
      right ventricular outflow tract, a posterior branch of the coronary sinus and in
      the right atrium. CONCLUSION: Congenital anomalies of thoracic veins may
      complicate lead placement on the appropriate and stable position. The presented
      case demonstrates a successful biventricular pacing and defibrillator therapy
      device implantation in a patient with dilated cardiomyopathy and severe heart
      failure.

PMID- 24450265
TI  - The 60th anniversary of the discovery of DNA secondary structure.

PMID- 24450266
TI  - Two original articles in the field of sleep medicine published in 1932 and 1934
      by the authors from the Faculty of Medicine in Belgrade (on the occasion of the
      90th anniversary of neuropsychiatric service in Serbia).

PMID- 24450267
TI  - [Updated ethical guidelines for clinical trials].

PMID- 24450268
TI  - [Riociguat - a stimulator of soluble guanylate cyclase: a new mode of action
      helps patients with pulmonary hypertension].

PMID- 24450270
TI  - [Controversies in the management of type 2 diabetes].
AB  - The new national guideline for the management of type 2 diabetes recommends
      procedures for the diagnosis and treatment of the metabolic disease. However, the
      contributing medical associations could not agree on some questions. Above all,
      there is a dissent which drug to choose, if metformin cannot be used or does not
      suffice in monotherapy.

PMID- 24450269
TI  - [Integrase inhibitors - new challenges for the treatment of HIV-1 infections].
AB  - Integrase inhibitors are a promising new group of antiretroviral drugs that
      suppress the integrase yielded by human immunodeficiency viruses (HIV) via
      inhibiting the ,,integration" of the viral deoxyribonucleic acid (DNA) into the
      hosts' DNA genome. In 2007, raltegravir was the first integrase inhibitor that
      has been approved for the treatment of HIV-1 infections in antiretroviral
      pretreated (-experienced) and antiretroviral-naive patients. Recently,
      elvitegravir, as a fixed coformulation with cobicistat, tenofovir und
      emtricitabine, has been approved for the treatment of HIV-1-infected
      antiretroviral-naive patients. InAugust of 2013, dolutegravir, a third integrase
      inhibitor, has been approved by the US Food and Drug Adiministation (FDA) for the
      treatment of HIV-1 infections in adults and children aged 12 years and older.
      Raltegravir has to be applied twice daily without a boosting agent. Elvitegravir
      and dolutegravir are applied once daily in the presence of a booster
      (elvitegravir) or unboosted (dolutegravir). In contrast to raltegravir and
      elvitegravir, dolutegravir shows a high genetic barrier to resistance, and is
      also applicable for the treatment of several HIV-1 infections with raltegravir
      and elvitegravir-resistant HIV variants. During the last years, raltegravir,
      elvitegravir and dolutegravir have been proven and established in the
      antiretroviral treatment of HIV-1 infections as effective, safe and well
      tolerated agents. However, reliable statement forecasts of long-term toxicity of
      these substances can not yet be made.

PMID- 24450271
TI  - [Can breastfeeding affect the effectiveness of rotavirus vaccination?].

PMID- 24450272
TI  - [Prevention through closure of a patent foramen ovale].

PMID- 24450273
TI  - CXCL12-CXCR7 signaling activates ERK and Akt pathways in human choriocarcinoma
      cells.
AB  - Abstract CXCL12 acts as a physiological ligand for the chemokine receptor CXCR7.
      Chemokine receptor expression by human trophoblast and other placental cells have
      important implications for understanding the regulation of placental growth and
      development. We had previously reported the differential expression of CXCR7 in
      different stages of the human placenta suggesting its possible role in regulation
      of placental growth and development. In this study, we determined the expression
      of CXCR7 in human choriocarcinoma JAR cells at the mRNA level and protein level
      and the downstream signaling pathway mediated by CXCL12-CXCR7 interaction. We
      observed that binding of CXCL12 to CXCR7 activates the ERK and Akt cell-survival
      pathways in JAR cells. Inhibition of the ERK and Akt pathways using specific
      inhibitors (Wortmanin & PD98509) led to the activation of the p38 pathway. Our
      findings suggest a possible role of CXCR7 in activating the cell survival
      pathways ERK and Akt in human choriocarcinoma JAR cells. 

PMID- 24450274
TI  - Women's autonomy in negotiating safer sex to prevent HIV: findings from the 2011
      Nepal Demographic and Health Survey.
AB  - Women with greater autonomy have higher HIV-related knowledge and condom use.
      Inability to negotiate safer sex in high-risk situations might increase HIV
      infection. This study examined the relationship between women's autonomy and
      ability to negotiate safer sex practices among married women. The 2011 Nepal
      Demographic and Health Survey data were used. The data were collected by two
      stage stratified cluster sampling and face-to-face interviews. Autonomy was
      measured in Decision-Making Participation and Assets Ownership, while ability to
      negotiate safer sex consists of Refusal of Sex and Ask for Condom Use. Among
      12,674 women of 15-49 years, married women were analyzed (n = 8,896). Women with
      greater autonomy in decision-making participation were more likely to negotiate
      safer sex. After controlling for socio-demographic factors, odds ratios (OR) for
      refusal of sex was 2.70 (95% CI [2.14, 3.40]) in women with the highest decision
      making participation. These women showed higher OR for 'ask for condom use' in
      high risk situations (2.10, 95% CI [1.81, 2.44]). Assets ownership also
      demonstrated a positive statistical relationship with asking for a condom use (OR
      1.31, 95% CI [1.10, 1.56]). The results point to the importance of women's
      autonomy on sexual health. It emphasizes women's empowerment-based approach to
      curbing HIV/AIDS in developing countries. 

PMID- 24450275
TI  - A systematic review of microfinance-based interventions for HIV/AIDS prevention.
AB  - The aim of this study is to describe the scope of microfinance-based
      interventions for HIV/AIDS prevention. A systematic review was carried out of
      literature published between 1986 and 2012 from EBSCO, ProQuest, Science Direct,
      Emerald, and JSTOR. The search included original research articles that presented
      evaluated interventions. Books, dissertations, gray literature, and theoretical
      reviews were excluded. Findings revealed a total of fourteen studies focused on
      the evaluation of: the IMAGE project, female sex workers, life skills and risk
      behavior reduction, adherence to treatment, and children and their families. Most
      of these interventions have shown to have beneficial effects, although results
      depend on: the type of program, monitoring, sustainability of microcredits, and
      contextual conditions. The findings of this review should be complemented with
      interventions carried out by various NGOs and microfinance institutions in
      different countries that present their results in a dissimilar way. 

PMID- 24450276
TI  - An intervention to reduce HIV-related stigma in partnership with African American
      and Latino churches.
AB  - HIV-related stigma negatively affects prevention and care, and community-based
      interventions are needed. Here we describe the development of a multi-ethnic,
      faith-based intervention to reduce HIV stigma that included: educational
      workshops on HIV, testing, and stigma; peer leader workshops using role plays and
      drawing on principles of motivational interviewing; a pastor-delivered sermon on
      HIV that incorporated theological reflection and an imagined contact scenario;
      and congregation-based HIV testing events. Lessons learned include: partnership
      development is essential and requires substantial investment; tailoring
      intervention components to single race-ethnic groups may not be preferable in
      diverse community settings; and adapting testing processes to be able to serve
      larger numbers of people in shorter time frames is needed for congregational
      settings. This development process successfully combined the rigorous application
      of social science theory and community engagement to yield a multifaceted HIV
      stigma reduction intervention appropriate for Protestant and Catholic churches in
      African American and Latino communities. 

PMID- 24450277
TI  - Promoting cancer prevention and control in community-based HIV/AIDS service
      organizations: are they ready?
AB  - Community-based organizations (CBOs) serving persons living with HIV or AIDS face
      the challenge of an aging population with more chronic diseases. This study
      assessed cancer programming needs of AIDS service organizations (ASOs) in New
      York, New Jersey, and Connecticut by conducting a community needs assessment.
      Sixty (58%) of 103 organizations completed the survey. ASOs conduct activities
      most related to early steps along the cancer care continuum, but they also
      express great interest in expanding cancer-focused programming into new areas.
      ASOs have resources or capacities in assisting HIV+ clients with mental health or
      substance abuse problems, but there exists a need for funding in undertaking or
      expanding cancer-focused programs. ASOs are receptive to collaborating with
      researchers on disseminating cancer prevention and control knowledge in their
      settings. Community-academic research partnerships enable resonant training and
      technical assistance methods to be explored that will enhance the abilities of
      ASOs to bring cancer-related programming to their clients. 

PMID- 24450278
TI  - Finding and recruiting the highest risk HIV-negative men who have sex with men.
AB  - This study compared the ability of different field and online recruitment venues
      to reach those at highest risk for HIV infection among HIV-negative men who have
      sex with men (MSM), given that some subgroups are difficult to reach, and venues
      vary in the demographic characteristics of the samples they yield. Compared to
      other venues, dating/hookup websites reached significantly higher-than-expected
      concentrations of White MSM aged 40 and above, including those who reported
      unprotected anal intercourse (UAI). Facebook was the most successful venue for
      the recruitment of MSM who used stimulants, including those who reported UAI. MSM
      who reported UAI were more likely to be recruited online. This study points to
      systematic variation in the samples obtained via different recruitment
      strategies, which should be taken into consideration when designing
      intervention/prevention programs targeting HIV-negative MSM. 

PMID- 24450279
TI  - Adaptation and implementation of HoMBReS: a community-level, evidence-based HIV
      behavioral intervention for heterosexual Latino men in the midwestern United
      States.
AB  - Over the past decade, the midwestern United States has witnessed a dramatic
      increase in its Latino population. The lack of culturally and linguistically
      congruent resources coupled with high incidence and prevalence rates of HIV among
      Latinos living in the Midwest merits attention. HoMBReS: Hombres Manteniendo
      Bienestar y Relaciones Saludables (Men Maintaining Wellbeing and Healthy
      Relationships) is a community-level social network intervention designed for
      Latino men. We describe the adaptation and implementation of HoMBReS for Latino
      men living in Indianapolis, Indiana, the second largest city in the Midwest. Five
      Navegantes (lay health educators) were trained; they provided a total of 34
      educational charlas (small group didactic sessions). A total of 270 Latino men
      attended the charlas and were offered no-cost screening for HIV and sexually
      transmitted infections (STI). Three participants tested HIV positive and 15
      screened positive for STI. The charlas coupled with the testing initiative,
      served as a successful method to increase sexual health knowledge among Latino
      men and to link newly-diagnosed HIV/STI-positive individuals to treatment and
      care. The adaptation and implementation of HoMBReS respond to the CDC and NIH
      call to increase HIV testing and service provision among vulnerable populations. 

PMID- 24450280
TI  - HIV testing in primary care: feasibility and acceptability of provider initiated
      HIV testing and counseling for sub-Saharan African migrants.
AB  - Provider-initiated HIV testing and counseling (PITC) is recommended to reduce
      late HIV diagnoses, common among Sub-Saharan African migrants (SAM) residing in
      Europe. Primary care represents an ideal entry point for PITC. To support Flemish
      general practitioners (GPs), we developed a culturally sensitive PITC tool. Over
      a 12-week period, 65 GPs implemented PITC to assess acceptability and feasibility
      of PITC. The qualitative evaluation showed high acceptability among physicians.
      Routine PITC was challenged by physicians' personal discomfort, assumptions of
      patients' sexual risk, perceived incoherence with reasons for consultation, and
      time pressure. The best opportunity for PITC was an indicated blood analysis for
      other medical reasons. Counseling skills improved during the implementation, but
      participants still advocated for reduced counseling requirements. PITC proved to
      be feasible in primary care settings, but the up-scaling requires a reformulation
      of counseling guidelines, a policy stipulating the role of GPs in the prevention
      care continuum, and an investment in (continuous) training. 

PMID- 24450281
TI  - Optimal dialysate sodium-what is the evidence?
AB  - Oligo-anuric patients with end-stage kidney disease are dependent on hemodialysis
      to achieve and maintain the desired goal of euvolemia. The dialysis prescription,
      in addition to sodium and fluid restriction, is therefore a critically important
      factor in the care of hemodialysis patients. Various dialysate sodium
      concentrations have been favored throughout the history of dialysis, but the
      "optimal" concentration remains unclear. In this manuscript, we examine the
      historical context of changes to the dialysate sodium prescription, review the
      evidence of its associated effects, discuss 'individualization' of dialysate
      sodium, and highlight the need for definitive trials that are powered for
      important clinical outcomes. 

PMID- 24450282
TI  - Universal quantifier derived from AFM analysis links cellular mechanical
      properties and cell-surface integration forces with microbial deposition and
      transport behavior.
AB  - In this study, we employed AFM analysis combined with mathematical modeling for
      quantifying cell-surface contact mechanics and magnitude and range of cell
      surface interaction forces for seven bacterial strains with a wide range of cell
      morphology, dimension, and surface characteristics. Comprehensive cell-surface
      characterization including surface charge, extracellular polymeric substance
      content, hydrophobicity, and cell-cell aggregation analyses were performed. Flow
      through column tests were employed to determine the attachment efficiency and
      deposition-transport behavior of these bacterial strains. No statistically
      significant correlation between attachment efficiency and any single-cell surface
      property was identified. Single-cell characterization by atomic force microscopy
      (AFM) yielded the mechanical deformation and elastic modulus, penetration
      resistance to AFM probe penetration by cellular surface substances (CSS), range
      and magnitude of the repulsive-attractive intersurface forces, and geometry of
      each strain. We proposed and derived a universal dimensionless modified Tabor's
      parameter to integrate all these properties that account for their collective
      behavior. Results showed that the Tabor parameter derived from AFM analysis
      correlated well with experimentally determined attachment efficiency (alpha),
      which therefore is able to link microscale cell-surface properties with
      macroscale bacterial transport behavior. Results suggested that the AFM tests
      performed between a single cell and a surface captured the key quantities of the
      interactions between the cell and the surface that dictate overall cell
      attachment behavior. Tabor's parameter therefore can be potentially incorporated
      into the microbial transport model. 

PMID- 24450283
TI  - Seventh meeting of the Global Alliance to Eliminate Lymphatic Filariasis:
      reaching the vision by scaling up, scaling down, and reaching out.
AB  - This report summarizes the 7th meeting of the Global Alliance to Eliminate
      Lymphatic Filariasis (GAELF), Washington DC, November 18-19, 2012. The theme, "A
      Future Free of Lymphatic Filariasis: Reaching the Vision by Scaling Up, Scaling
      Down and Reaching Out", emphasized new strategies and partnerships necessary to
      reach the 2020 goal of elimination of lymphatic filariasis (LF) as a public
      health problem. 

PMID- 24450284
TI  - Cubital subchondral joint space width and CT osteoabsorptiometry in dogs with and
      without fragmented medial coronoid process.
AB  - OBJECTIVE: To evaluate subchondral joint space width measurements (SJSW) and CT
      osteoabsorptiometry (CTOAM) measurements in the elbow of dogs with naturally
      occurring fragmented medial coronoid process (FMCP) preoperatively and 6 months
      postoperatively, and to compare these to normal dogs. STUDY DESIGN: Prospective
      randomized clinical trial. ANIMALS: Large breed dogs <1 year of age (n = 15).
      METHODS: Arthroscopic FMCP debridement was performed, followed by randomization
      to a proximal ulnar ostectomy with IM pin (PUO). CTs were performed pre
      operatively and 6 months post-operatively. CTOAM and SJSW measurements were
      acquired in 7 locations within the joint and compared to an age-matched normal
      control group. Pearson correlation was performed on SJSW and CTOAM measurements.
      A linear mixed model determined the effect of disease and treatment on SJSW and
      CTOAM measurements. RESULTS: Fifteen dogs (28 elbows) with FMCP participated (11
      arthroscopic FMCP removal, 17 with additional PUO). Data were normally
      distributed. Pearson correlation between CTOAM and SJSW measurements showed
      moderate to strong negative correlation in the control dogs. Preoperatively,
      affected elbows had lower medial compartment and higher lateral coronoid process
      CTOAM values than normal elbows. After treatment, CTOAM values of the medial
      compartment increased to normal. Treatment with PUO did not affect SJSW or CTOAM.
      CONCLUSIONS: Our data agree with these previous studies suggesting lower
      subchondral plate mineralization in dogs affected by FMCP. Arthroscopy may result
      in higher CTOAM values secondary to increased loading.

PMID- 24450285
TI  - Three-dimensional surgical navigation model with TilePro display during robot
      assisted radical prostatectomy.
AB  - Abstract To facilitate robotic nerve-sparing radical prostatectomy, we developed
      a novel three-dimensional (3D) surgical navigation model that is displayed on the
      TilePro function of the da Vinci(r) surgeon console. Based on 3D transrectal
      ultrasonography (TRUS)-guided prostate biopsies, we reconstructed a 3D model of
      the TRUS-visible, histologically confirmed "index" cancer lesion in 10
      consecutive patients. Five key anatomic structures (prostate, image-visible
      biopsy-proven "index" cancer lesion, neurovascular bundles, urethra, and recorded
      biopsy trajectories) were image-fused and displayed onto the TilePro function of
      the robotic console. The 3D model facilitated careful surgical dissection in the
      vicinity of the biopsy-proven index lesion. Geographic location of the index
      lesion on the final histology report correlated with the software-created 3D
      model. Negative surgical margins were achieved in 90%, except for one case with
      extensive extra-prostate extension. At postoperative 3 months, prostate-specific
      antigen levels were undetectable (<0.03 ng/mL) in all cases. The initial
      experience of the navigation model is presented. 

PMID- 24450286
TI  - Characterization of intracellular regions in the human serotonin transporter for
      phosphorylation sites.
AB  - In the central nervous system, synaptic levels of the monoamine neurotransmitter
      serotonin are mainly controlled by the serotonin transporter (SERT), and drugs
      used in the treatment of various psychiatric diseases have SERT as primary
      target. SERT is a phosphoprotein that undergoes phosphorylation/dephosphorylation
      during transporter regulation by multiple pathways. In particular, activation
      and/or inhibition of kinases including PKC, PKG, p38MAPK, and CaMKII modulate
      SERT function and trafficking. The molecular mechanisms by which kinase activity
      is linked to SERT regulation are poorly understood, including the identity of
      specific phosphorylated residues. To elucidate SERT phosphorylation sites, we
      have generated peptides corresponding to the entire intracellular region of human
      SERT and performed in vitro phosphorylation assays with a panel of kinases
      suggested to be involved in SERT regulation or for which canonical
      phosphorylation sites are predicted. Peptide analysis by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) was used to identify and quantify site
      specific phosphorylation. Five residues located in the N- and C-termini and in
      intracellular loop 1 and 2 were identified as phosphorylation sites; Ser149,
      Ser277, and Thr603 for PKC, Ser13 for CaMKII, and Thr616 for p38MAPK. Possible
      regulatory roles of these potential phosphoacceptors for SERT function and
      surface expression were investigated using phospho-mimicking and phosphodeficient
      mutations, coexpression of constitutively active kinases and pharmacological
      kinase induction in a heterologous expression system. Our results suggest that
      Ser277 is involved in an initial phase of PKC-mediated down-regulation of SERT.
      The five identified sites can guide future studies of direct links between SERT
      phosphorylation and regulatory processes. 

PMID- 24450287
TI  - Unification of methods for estimating the strength of reproductive isolation.
AB  - Understanding the evolution of reproductive isolation is tantamount to describing
      the origin of species. Therefore, a primary goal in evolutionary biology is to
      identify which reproductive barriers are most important to the process. To
      achieve this goal, the strength of multiple forms of isolation must be compared
      in an equivalent manner. However, a diversity of methods has been used to
      estimate barrier strength, falling into several mathematically distinct
      categories. This study provides a unified method for calculating isolation that
      relates the amount of gene flow experienced by taxa to random expectations in a
      simple linear framework. This approach has three distinct advantages over
      previous methods: (1) it is directly related to gene flow, (2) it is symmetrical,
      such that measures in both the positive and negative range are comparable, and
      (3) it is equivalent between broad categories of reproductive isolation, allowing
      for appropriate comparisons. This linear formulation can be adjusted for use in
      all forms of isolation, and can accommodate cases in which null expectations for
      con- and heterospecific gene flow differ. Additionally, this framework can be
      used to calculate total reproductive isolation and the relative contributions of
      individual barriers. 

PMID- 24450288
TI  - Active blood parasite infection is not limited to the breeding season in a
      declining farmland bird.
AB  - Avian blood parasites can have significant impacts on adult breeding birds but
      studies of parasitism outside the breeding season are rare, despite their
      potentially important implications for host-parasite dynamics. Here we
      investigate temporal dynamics of blood parasite infection in adult yellowhammers
      Emberiza citrinella . We screened blood samples collected between December and
      April of 2 consecutive winters using PCR. We found a high prevalence of both
      Haemoproteus and Leucocytozoon parasites, with a mean prevalence of 50% across 2
      winters. Prevalence of both parasites was higher during the second, colder winter
      of the study. Temporal trends differed between the 2 genera, suggesting that
      chronic Haemoproteus infections gradually disappear throughout the winter but
      that Leucocytozoon infections exhibit a relapse during late winter, possibly
      coincident with reduced food availability. Our results highlight the difference
      in temporal dynamics between 2 blood parasite genera infecting the same host
      population and emphasize the need for accurate assessment of infection status at
      appropriate time periods when examining impacts of, and associations with, blood
      parasite infection. We suggest that further research should investigate the
      implications of over-winter infection for birds' physiology, behavior, and
      survival.

PMID- 24450289
TI  - Prevalence and assessment of breathlessness in the clinical setting.
AB  - Breathlessness is a common symptom in the general population and a frequent
      reason for presentation in all healthcare settings. It causes serious functional
      limitations, distress for both patient and carer, and predicts poor clinical
      outcomes. Traditionally, clinical care focuses on investigation, diagnosis and
      treatment of the conditions causing breathlessness. Breathlessness itself is
      often not seen as a target for therapeutic interventions by either clinician or
      patient, and so breathlessness which persists despite optimum treatment of the
      condition is self-managed by the patient without medical help. There are evidence
      based interventions which benefit breathlessness, irrespective of its cause;
      systematic assessment should lead to individually tailored management plans. A
      simple measure of severity (intensity) and assessment of bother or distress
      caused by breathlessness in addition to the impact on quality of life should be
      routinely sought in a proactive manner so that appropriate management plans can
      be put in place. 

PMID- 24450290
TI  - Gastrointestinal symptoms before and during menses in healthy women.
AB  - BACKGROUND: Little is known as to the extent gastrointestinal (GI) complaints are
      reported by women around menses. We aimed to describe GI symptoms that occurred
      premenstrually and during menses in healthy women, and to specifically assess the
      relationship of emotional symptoms to GI symptoms around menses. METHODS: We
      recruited healthy, premenopausal adult women with no indication of GI,
      gynecologic, or psychiatric disease who were attending an outpatient gynecology
      clinic for well-woman care. They completed a survey that queried menstrual
      histories and the presence of GI and emotional symptoms. We compared the
      prevalence of primary GI symptoms (abdominal pain, diarrhea, constipation,
      nausea, vomiting), as well as pelvic pain and bloating, in the 5 days preceding
      menses and during menses, and assessed whether emotional symptoms or other
      factors were associated with the occurrence of GI symptoms. RESULTS: Of 156
      respondents, 73% experienced at least one of the primary GI symptoms either pre-
      or during menses, with abdominal pain (58% pre; 55% during) and diarrhea (24%
      pre; 28% during) being the most common. Those experiencing any emotional symptoms
      versus those without were more likely to report multiple (2 or more) primary GI
      symptoms, both premenstrually (depressed p = 0.006; anxiety p = 0.014) and during
      menses (depressed p < 0.001; anxiety p = 0.008). Fatigue was also very common
      (53% pre; 49% during), and was significantly associated with multiple GI symptoms
      in both menstrual cycle phases (pre p < 0.001; during p = 0.01). CONCLUSIONS:
      Emotional symptoms occurring in conjunction with GI symptoms are common
      perimenstrually, and as such may reflect shared underlying processes that
      intersect brain, gut, and hormonal pathways.

PMID- 24450292
TI  - Shotgun proteomic analysis of porcine colostrum and mature milk.
AB  - The epitheliochorial nature of the porcine placenta prevents the transfer of
      maternal immunity. Therefore, ingestion of the colostrum immediately after birth
      is crucial for neonatal piglets to acquire passive immunity from the sow. We
      performed a shotgun proteomic analysis of porcine milk to reveal in detail the
      protein composition of porcine milk. On the basis of the Swiss-Prot database, 113
      and 118 proteins were identified in the porcine colostrum and mature milk,
      respectively, and 50 of these proteins were common to both samples. Some immune
      related proteins, including interleukin-18 (IL-18), were unique to the colostrum.
      The IL-18 concentration in the colostrum and mature milk of four sows was
      measured to validate the proteomic analysis, and IL-18 was only detected in the
      colostrum (191.0 +/- 53.9 pg/mL) and not in mature milk. In addition, some
      proteins involved in primary defense, such as azurocidin, which has never been
      detected in any other mammal's milk, were also identified in the colostrum. 

PMID- 24450293
TI  - Effects of stifle flexion angle and scan plane on visibility of the normal canine
      cranial cruciate ligament using low-field magnetic resonance imaging.
AB  - Low-field magnetic resonance imaging (MRI) is commonly used to evaluate dogs with
      suspected cranial cruciate ligament injury; however, effects of stifle
      positioning and scan plane on visualization of the ligament are incompletely
      understood. Six stifle joints (one pilot, five test) were collected from dogs
      that were scheduled for euthanasia due to reasons unrelated to the stifle joint.
      Each stifle joint was scanned in three angles of flexion (90 degrees , 135
      degrees , 145 degrees ) and eight scan planes (three dorsal, three axial, two
      sagittal), using the same low-field MRI scanner and T2-weighted fast spin echo
      scan protocol. Two experienced observers who were unaware of scan technique
      independently scored visualization of the cranial cruciate ligament in each scan
      using a scale of 0-3. Visualization score rank sums were higher when the stifle
      was flexed at 90 degrees  compared to 145 degrees , regardless of the scan plane.
      Visualization scores for the cranial cruciate ligament in the dorsal (H (2) =
      19.620, P = 0.000), axial (H (2) = 14.633, P = 0.001), and sagittal (H (2) =
      8.143, P = 0.017) planes were significantly affected by the angle of stifle
      flexion. Post hoc analysis showed that the ligament was best visualized at 90
      degrees  compared to 145 degrees  in the dorsal (Z = -3.906, P = 0.000), axial (Z
      = -3.398, P = 0.001), and sagittal (Z = -2.530, P = 0.011) planes. Findings
      supported the use of a 90 degrees  flexed stifle position for maximizing
      visualization of the cranial cruciate ligament using low-field MRI in dogs. 

PMID- 24450291
TI  - Is the inflammasome a potential therapeutic target in renal disease?
AB  - The inflammasome is a large, multiprotein complex that drives proinflammatory
      cytokine production in response to infection and tissue injury. Pattern
      recognition receptors that are either membrane bound or cytoplasmic trigger
      inflammasome assembly. These receptors sense danger signals including damage
      associated molecular patterns and pathogen-associated molecular patterns (DAMPS
      and PAMPS respectively). The best-characterized inflammasome is the NLRP3
      inflammasome. On assembly of the NLRP3 inflammasome, post-translational
      processing and secretion of pro-inflammatory cytokines IL-1beta and IL-18 occurs;
      in addition, cell death may be mediated via caspase-1. Intrinsic renal cells
      express components of the inflammasome pathway. This is most prominent in tubular
      epithelial cells and, to a lesser degree, in glomeruli. Several primary renal
      diseases and systemic diseases affecting the kidney are associated with NLRP3
      inflammasome/IL-1beta/IL-18 axis activation. Most of the disorders studied have
      been acute inflammatory diseases. The disease spectrum includes ureteric
      obstruction, ischaemia reperfusion injury, glomerulonephritis, sepsis, hypoxia,
      glycerol-induced renal failure, and crystal nephropathy. In addition to mediating
      renal disease, the IL-1/ IL-18 axis may also be responsible for development of
      CKD itself and its related complications, including vascular calcification and
      sepsis. Experimental models using genetic deletions and/or receptor
      antagonists/antiserum against the NLRP3 inflammasome pathway have shown decreased
      severity of disease. As such, the inflammasome is an attractive potential
      therapeutic target in a variety of renal diseases. 

PMID- 24450294
TI  - Gene therapy and cell reprogramming for the aging brain: achievements and
      promise.
AB  - In the central nervous system, cholinergic and dopaminergic (DA) neurons are
      among the cells most susceptible to the deleterious effects of age. Thus, the
      basal forebrain cholinergic system is known to undergo moderate neurodegenerative
      changes during normal aging as well as severe atrophy in Alzheimer's disease
      (AD). Parkinson's disease (PD), a degeneration of nigro-striatal DA neurons is
      the most conspicuous reflection of the vulnerability of DA neurons to age.
      Overall, there is growing evidence that a progressive decline in cognitive
      function and central DA activity represents basic features of normal aging both
      in humans and laboratory rodents. Spontaneous or environmental neurotoxin
      mediated exacerbation of these processes contributes to the symptoms of AD and
      PD, respectively. In this context, neurotrophic factors that can prevent or delay
      the decline in cognitive function and central DA activity are of clinical
      interest. Among them, Insulin-like Growth Factor I and Glial cell line-Derived
      Neurotrophic Factor are emerging as powerful neuroprotective molecules. This
      article discusses the experimental evidence supporting the neuroprotective
      relevance of these and related factors in the aging brain. The availability of
      induced pluripotent stem cells offers a new promise for the treatment of
      pathologies associated with the loss of specific cell types as for instance,
      nigral DA neurons (in PD) or basal forebrain cholinergic neurons (BFCN) in the
      early stages of AD. Recent studies documenting the use of cell reprogramming for
      the generation of multipotent neuronal precursors as well as functional BFCN and
      DA neurons are reviewed. 

PMID- 24450297
TI  - Extension and limits of the network of coupled motions correlated to hydride
      transfer in dihydrofolate reductase.
AB  - Enzyme catalysis has been studied extensively, but the role of enzyme dynamics in
      the catalyzed chemical conversion is still an enigma. The enzyme dihydrofolate
      reductase (DHFR) is often used as a model system to assess a network of coupled
      motions across the protein that may affect the catalyzed chemical transformation.
      Molecular dynamics simulations, quantum mechanical/molecular mechanical studies,
      and bioinformatics studies have suggested the presence of a "global dynamic
      network" of residues in DHFR. Earlier studies of two DHFR distal mutants, G121V
      and M42W, indicated that these residues affect the chemical step synergistically.
      While this finding was in accordance with the concept of a network of functional
      motions across the protein, two residues do not constitute a network. To better
      define the extent and limits of the proposed network, the current work studied
      two remote residues predicted to be part of the same network: W133 and F125. The
      effect of mutations in these residues on the nature of the chemical step was
      examined via measurements of the temperature-dependence of the intrinsic kinetic
      isotope effects (KIEs) and other kinetic parameters, and double mutants were used
      to tie the findings to G121 and M42. The findings indicate that residue F125,
      which was implicated by both calculations and bioinformatic methods, is a part of
      the same global dynamic network as G121 and M42, while W133, implicated only by
      bioinformatics, is not. These findings extend our understanding of the proposed
      network and the relations between functional and genomic couplings. Delineating
      that network illuminates the need to consider remote residues and protein
      structural dynamics in the rational design of drugs and of biomimetic catalysts. 

PMID- 24450298
TI  - Interstitial pneumonia as an initial manifestation in a patient with late-onset
      SLE.

PMID- 24450299
TI  - Microbial load of umbilical cord blood Ureaplasma species and Mycoplasma hominis
      in preterm prelabor rupture of membranes.
AB  - OBJECTIVE: To evaluate Ureaplasma species and M. hominis DNA in the umbilical
      cord blood and its correlation with its microbial load in the amniotic fluid, as
      a measure of microbial burden in fetal inflammatory response and neonatal outcome
      in pregnancies complicated by preterm prelabor rupture of membranes (pPROM).
      STUDY DESIGN: A retrospective study of 158 women with singleton pregnancies
      complicated by pPROM between 24(0/7) and 36(6/7) weeks was conducted. Amniotic
      fluid was obtained from all women by transabdominal amniocentesis, and umbilical
      cord blood was obtained by venipuncture from umbilical cords immediately after
      the delivery of the neonates. The Ureaplasma species and M. hominis DNA was
      quantitated using absolute quantification techniques. RESULT: Ureaplasma species
      and M. hominis DNA was identified in 9% of the umbilical cord blood samples. No
      correlation between the amniotic fluid and umbilical cord blood microbial load
      was observed. The presence of Ureaplasma species and M. hominis DNA in the
      umbilical cord blood had no impact on short-term neonatal morbidity. CONCLUSIONS:
      A high microbial load of genital mycoplasma Ureaplasma species DNA in the
      umbilical cord in pregnancies complicated by pPROM is not associated with a high
      fetal inflammatory response and is therefore not associated with serious neonatal
      morbidity.

PMID- 24450300
TI  - Significance of sugar chain recognition by galectins and its involvement in
      disease-associated glycosylation.
AB  - Galectins are beta-galactoside-binding lectins that participate in a wide range
      of biological processes. Galectins are distributed both inside and outside cells
      and are believed to have roles in both intra- and extracellular milieus. One of
      the well-recognized functions of galectins is stabilization of glycoproteins on
      the cell surface, thereby promoting stable signal transduction and transport of
      substances such as glucose. Glycoprotein-associated diseases, including
      congenital disorder of glycosylation (CDG, previously called carbohydrate
      deficient glycoprotein syndrome), comprise a disease family established only in
      the last decade. Although numerous in vitro glycobiology studies have been
      performed, including investigation of glycan-galectin interactions and of
      galectin action in cultured cells, a few in vivo studies have investigated
      molecular mechanisms of galectin actions in animal models. Both in vitro and in
      vivo studies are needed in order to better determine the biological significance
      of sugar chain recognition. Hitherto, some reports have focused on the role of
      impaired sugar chain recognition and galectin function in the development of
      diverse diseases, including rheumatoid arthritis, diabetes mellitus, colitis, and
      cancer. We recently focused on the function of galectins in immunity and
      embryogenesis, and in this review we summarize the diseases related to disorders
      of sugar chain-galectin interaction and discuss the role of galectins as
      potential risk factors for some congenital and acquired diseases. These diseases
      are disorders of immunity, metabolism, and cell differentiation. This approach to
      understanding the significance of sugar chain recognition by galectins may open
      up a new field into the nature of glycoprotein-related diseases, including CDG. 

PMID- 24450301
TI  - Pregabalin does not affect sperm production in healthy volunteers: a randomized,
      double-blind, placebo-controlled, noninferiority study.
AB  - OBJECTIVE: The primary objective of this study was to compare the effects of
      pregabalin and placebo on sperm concentration in healthy male subjects. Changes
      in follicle-stimulating hormone (FSH), testosterone, sperm motility, semen
      volume, and sperm morphology were also examined. METHODS: This was a phase 4,
      multicenter, double-blind, randomized, placebo-controlled, noninferiority study.
      A 12-week treatment period (placebo or 600 mg/day of pregabalin) was followed by
      a 1-week taper period and a 13-week washout period. The primary outcome measure
      was the percentage of subjects with a >= 50% reduction from baseline in sperm
      concentration at End of Study. RESULTS: One hundred and nine subjects received
      placebo and 111 subjects received pregabalin. The difference between placebo and
      pregabalin with respect to the percentage of subjects with a >= 50% reduction
      from baseline in sperm concentration at End of Study was 6% (95% CI: -2.29 to
      14.3%). Noninferiority of pregabalin compared to placebo was declared as the
      upper bound of the 95% CI was less than the prespecified noninferiority margin of
      20%. There were no significant differences between placebo and pregabalin groups
      with respect to their effects on FSH, testosterone, or sperm motility. Changes in
      semen volume and sperm morphology were numerically similar in both treatment
      groups. Adverse events were consistent with the known safety profile of
      pregabalin. Treatment with 600 mg/day pregabalin for 12 weeks does not adversely
      affect spermatogenesis or serum levels of FSH and testosterone in healthy males.

PMID- 24450302
TI  - Human disturbance causes the formation of a hybrid swarm between two naturally
      sympatric fish species.
AB  - Most evidence for hybrid swarm formation stemming from anthropogenic habitat
      disturbance comes from the breakdown of reproductive isolation between incipient
      species, or introgression between allopatric species following secondary contact.
      Human impacts on hybridization between divergent species that naturally occur in
      sympatry have received considerably less attention. Theory predicts that
      reinforcement should act to preserve reproductive isolation under such
      circumstances, potentially making reproductive barriers resistant to human
      habitat alteration. Using 15 microsatellites, we examined hybridization between
      sympatric populations of alewife (Alosa pseudoharengus) and blueback herring (A.
      aestivalis) to test whether the frequency of hybridization and pattern of
      introgression have been impacted by the construction of a dam that isolated
      formerly anadromous populations of both species in a landlocked freshwater
      reservoir. The frequency of hybridization and pattern of introgression differed
      markedly between anadromous and landlocked populations. The rangewide frequency
      of hybridization among anadromous populations was generally 0-8%, whereas all
      landlocked individuals were hybrids. Although neutral introgression was observed
      among anadromous hybrids, directional introgression leading to increased
      prevalence of alewife genotypes was detected among landlocked hybrids. We
      demonstrate that habitat alteration can lead to hybrid swarm formation between
      divergent species that naturally occur sympatrically, and provide empirical
      evidence that reinforcement does not always sustain reproductive isolation under
      such circumstances. 

PMID- 24450304
TI  - Molecular diagnosis of primary immunodeficiency diseases in a developing country:
      Iran as an example.
AB  - Primary immunodeficiency diseases (PID) comprise a heterogeneous group of
      inherited diseases with a wide spectrum of clinical manifestations and laboratory
      abnormalities. Definite diagnosis of a PID is performed most reliably by
      detection of a gene mutation which will allow genetic counseling. In addition,
      detection and confirmation of PIDs that were not severe enough during childhood
      to lead to a specific diagnosis would be possible. As a definite diagnosis of PID
      is of importance for the management of these disorders, we present a review on
      studies that have investigated mutations among patients with different types of
      PID in Iran. Although the frequency of a definite molecular diagnosis of PID in
      Iran is acceptable in a developing country, we believe that providing additional
      laboratory resources and diagnostic methods, development of specialized centers
      for PID, in addition to improvement of physicians' awareness, may facilitate
      clinical and genetic diagnosis of patients with PID in Iran.

PMID- 24450305
TI  - Mechanism of orthotic therapy for the painful cavus foot deformity.
AB  - BACKGROUND: People who have extremely high arched feet or pes cavus often suffer
      from substantial foot pain. Custom-made foot orthoses (CFO) have been shown to be
      an effective treatment option, but their specificity is unclear. It is generally
      thought that one of the primary functions of CFO is redistributing abnormal
      plantar pressures. This study sought to identify variables associated with pain
      relief after CFO intervention. METHODS: Plantar pressure data from a randomized
      controlled trial of 154 participants with painful pes cavus were retrospectively
      re-analyzed at baseline and three month post CFO intervention. The participants
      were randomized to a treatment group given CFO or a control group given sham
      orthoses. RESULTS: No relationship between change in pressure magnitude and
      change in symptoms was found in either group. However, redistribution of plantar
      pressure, measured with the Dynamic Plantar Loading Index, had a significant
      effect on pain relief (p = 0.001). Our final model predicted 73% of the variance
      in pain relief from CFO and consisted of initial pain level, BMI, foot alignment,
      and changes in both Dynamic Plantar Loading Index and pressure-time integral.
      CONCLUSION: Our data suggest that a primary function of effective orthotic
      therapy with CFO is redistribution of abnormal plantar pressures. Results of this
      study add to the growing body of literature providing mechanistic support for CFO
      providing pain relief in painful foot conditions. The proposed model may assist
      in better designing and assessing orthotic therapy for pain relief in patients
      suffering painful cavus foot deformity. TRIAL REGISTRATION: Randomized controlled
      trial: ISRCTN84913516.

PMID- 24450306
TI  - Nystagmus as an early ocular alteration in Machado-Joseph disease (MJD/SCA3).
AB  - BACKGROUND: Machado-Joseph disease (MJD), also named spinocerebellar ataxia type
      3 (SCA3) is the most common autosomal dominant ataxia worldwide. Although
      nystagmus is one of the most frequently reported ocular alterations in MJD
      patients its behaviour during the course of the disease, namely in its early
      stages, has only recently started to be investigated. The main goal of this work
      was to characterize the frequency of nystagmus in symptomatic and presymptomatic
      carriers of the MJD mutation, and investigate its usefulness as an early
      indicator of the disease. METHODS: We conducted an observational study of Azorean
      MJD family members, comprising a total of 158 subjects which underwent
      neurological evaluation. Sixty eight were clinically and molecularly diagnosed
      with MJD, 48 were confirmed asymptomatic carriers and 42 were confirmed non
      carriers of the MJD mutation. The frequency of nystagmus was calculated for the 3
      groups. RESULTS: Nystagmus was present in 88% of the MJD patients. Seventeen
      percent of the at-risk subjects with a carrier result in the molecular test and
      none of the 42 individuals who received a non-carrier test result displayed
      nystagmus (p < 0.006). Although not reaching statistical significance,
      symptomatic subjects showing nystagmus had a tendency for a higher length of the
      CAG tract in the expanded allele, when compared to individuals who did not have
      nystagmus. CONCLUSIONS: The frequency of nystagmus in asymptomatic carriers and
      its absence in non-carriers of the mutation, suggests that nystagmus may appear
      before gait disturbance and can thus be considered an early sign of MJD.

PMID- 24450307
TI  - Characteristics of sexual violence against adolescent girls and adult women.
AB  - BACKGROUND: Sexual violence is considered a serious violation of human rights
      which affects mainly young women and adolescents. There is little information
      about the conditions under which sexual offences occur. We evaluated
      characteristics of sexual violence against adolescent girls and adult women.
      METHOD: This is a quantitative, retrospective, descriptive study of sexual
      violence against adolescent girls and adult women. Analyses were carried out on
      data collected from 1118 women, 546 adolescents (10-19 years) and 572 adults (>=
      20 years), with a complaint of rape treated at Hospital Perola Byington, Sao
      Paulo, between 1994 and 1999. The age limit of the adolescent sample met the
      World Health Organization's (WHO) criteria. We analyzed the type of sexual
      contact, degree of intimidation, perpetrator and activity of the victim during
      the approach. RESULTS: Crimes without penetration were five times more frequent
      in adolescents and use of threats of death or intimidation was common in both
      groups. Mental illness was more prevalent in adult victims and the majority of
      adolescent victims were aged <14 years. Uncle and stepfather perpetrators were
      more frequent among adolescents and partners or former intimate partners in adult
      women. In most cases the approach occurred in public places, although sex crimes
      at the perpetrator's residence were more frequent amongst adolescents.
      CONCLUSIONS: Although children and adolescents require the same intervention
      measures and legal protection, a considerable proportion of adolescent sex
      offenders can face conditions similar to those of adult women.

PMID- 24450308
TI  - Anoctamin 1 contributes to inflammatory and nerve-injury induced
      hypersensitivity.
AB  - BACKGROUND: Various pathological conditions such as inflammation or injury can
      evoke pain hypersensitivity. That represents the response to innocuous stimuli or
      exaggerated response to noxious stimuli. The molecular mechanism based on the
      pain hypersensitivity is associated with changes in many of ion channels in
      dorsal-root ganglion (DRG) neurons. Anoctamin 1 (ANO1/TMEM16A), a Ca2+ activated
      chloride channel is highly visible in small DRG neurons and responds to heat.
      Mice with an abolished function of ANO1 in DRG neurons demonstrated attenuated
      pain-like behaviors when exposed to noxious heat, suggesting a role in acute
      thermal nociception. In this study, we further examined the function of ANO1 in
      mediating inflammation- or injury-induced hyperalgesia or allodynia. RESULTS:
      Using Advillin/Ano1fl/fl (Adv/Ano1fl/fl) mice that have a functional ablation of
      Ano1 mainly in DRG neurons, we were able to determine its role in mediating
      thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve
      injury. The thermal hyperalgesia and mechanical allodynia induced by carrageenan
      injection and spared-nerve injury were significantly reduced in Adv/Ano1fl/fl
      mice. In addition, flinching or licking behavior after bradykinin or formalin
      injection was also significantly reduced in Adv/Ano1fl/fl mice. Since
      pathological conditions augment nociceptive behaviors, we expected ANO1's
      contribution to the excitability of DRG neurons. Indeed, the application of
      inflammatory mediators reduced the threshold for action potential (rheobase) or
      time for induction of the first action potential in DRG neurons isolated from
      control (Ano1fl/fl) mice. These parameters for neuronal excitability induced by
      inflammatory mediators were not changed in Adv/Ano1fl/fl mice, suggesting an
      active contribution of ANO1 in augmenting the neuronal excitability. CONCLUSIONS:
      In addition to ANO1's role in mediating acute thermal pain as a heat sensor, ANO1
      is also capable of augmenting the excitability of DRG neurons under inflammatory
      or neuropathic conditions and thereby aggravates inflammation- or tissue injury
      induced pathological pain.

PMID- 24450309
TI  - Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid
      lowering treatment.
AB  - BACKGROUND: Vitamin D deficiency has been linked to several cardiovascular risk
      factors but information regarding vitamin D concentrations in familial combined
      hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D
      concentrations in patients with FCHL and to study the effects of lipid-lowering
      therapy. METHODS: We conducted a cross sectional study on 59 patients with FCHL
      and 48 healthy controls. We analyzed 25-hydroxyvitamin D (25(OH)D) concentrations
      and their association with lipid parameters, anthropometric measures, C-reactive
      protein and homeostasis model assessment (HOMA) index. Twenty-three patients with
      FCHL were also included in a longitudinal study conducted to analyze 25
      hydroxyvitamin D concentrations before and after treatment for dyslipidemia.
      RESULTS: After adjustment for body mass index and seasonality, patients with FCHL
      had lower vitamin D concentrations than controls. Adjusted means (standard error
      of the mean (S.E.M)) for 25(OH)D according to the presence or absence of FCHL
      were 62.8 (3.6) nmol/L for patients with FCHL and 74.8 (4.1) nmol/L for controls
      (p = 0.021). In FCHL, hypovitaminosis D was associated with features of
      atherogenic dyslipidemia. After lipid-lowering therapy, vitamin D concentrations
      increased (51.0 +/- 31.3 to 58.9 +/- 24.6 nmol/L (P = 0.022)). However, changes
      in 25(OH)D concentrations did not correlate with changes in other parameters.
      CONCLUSIONS: Our findings suggest that FCHL is associated with decreased vitamin
      D concentrations and that treatment for dyslipidemia improves vitamin D status
      through an unknown mechanism. Further studies are needed to replicate these data
      in larger populations and to elucidate the mechanisms involved in this
      association.

PMID- 24450310
TI  - Convergence and translation: attitudes to inter-professional learning and
      teaching of creative problem-solving among medical and engineering students and
      staff.
AB  - BACKGROUND: Healthcare worldwide needs translation of basic ideas from
      engineering into the clinic. Consequently, there is increasing demand for
      graduates equipped with the knowledge and skills to apply interdisciplinary
      medicine/engineering approaches to the development of novel solutions for
      healthcare. The literature provides little guidance regarding barriers to, and
      facilitators of, effective interdisciplinary learning for engineering and medical
      students in a team-based project context. METHODS: A quantitative survey was
      distributed to engineering and medical students and staff in two universities,
      one in Ireland and one in Belgium, to chart knowledge and practice in
      interdisciplinary learning and teaching, and of the teaching of innovation.
      RESULTS: We report important differences for staff and students between the
      disciplines regarding attitudes towards, and perceptions of, the relevance of
      interdisciplinary learning opportunities, and the role of creativity and
      innovation. There was agreement across groups concerning preferred learning,
      instructional styles, and module content. Medical students showed greater
      resistance to the use of structured creativity tools and interdisciplinary teams.
      CONCLUSIONS: The results of this international survey will help to define the
      optimal learning conditions under which undergraduate engineering and medicine
      students can learn to consider the diverse factors which determine the success or
      failure of a healthcare engineering solution.

PMID- 24450311
TI  - Exploring social cognition in patients with apathy following acquired brain
      damage.
AB  - BACKGROUND: Research on cognition in apathy has largely focused on executive
      functions. To the best of our knowledge, no studies have investigated the
      relationship between apathy symptoms and processes involved in social cognition.
      Apathy symptoms include attenuated emotional behaviour, low social engagement and
      social withdrawal, all of which may be linked to underlying socio-cognitive
      deficits. METHODS: We compared patients with brain damage who also had apathy
      symptoms against similar patients with brain damage but without apathy symptoms.
      Both patient groups were also compared against normal controls on key socio
      cognitive measures involving moral reasoning, social awareness related to making
      judgements between normative and non-normative behaviour, Theory of Mind
      processing, and the perception of facial expressions of emotion. We also
      controlled for the likely effects of executive deficits and depressive symptoms
      on these comparisons. RESULTS: Our results indicated that patients with apathy
      were distinctively impaired in making moral reasoning decisions and in judging
      the social appropriateness of behaviour. Deficits in Theory of Mind and
      perception of facial expressions of emotion did not distinguish patients with
      apathy from those without apathy. CONCLUSION: Our findings point to a possible
      socio-cognitive profile for apathy symptoms and provide initial insights into how
      socio-cognitive deficits in patients with apathy may affect social functioning.

PMID- 24450312
TI  - Case Title: 45 year-old male with recurrent angioedema: WAO international case
      based discussions.

PMID- 24450314
TI  - Mental health issues in the pediatric population.

PMID- 24450313
TI  - A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010:
      the relationship between industry sponsorship and randomized study design.
AB  - BACKGROUND: The proportion of clinical research sponsored by industry will likely
      continue to expand as federal funds for academic research decreases, particularly
      in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to
      burden the US population, insufficient data exists as to how industry sponsorship
      affects clinical trials involving these infectious diseases. Debate exists about
      whether pharmaceutical companies undertake more market-driven research practices
      to promote therapeutics, or instead conduct more rigorous trials than their non
      industry counterparts because of increased resources and scrutiny. The
      ClinicalTrials.gov registry, which allows investigators to fulfill a federal
      mandate for public trial registration, provides an opportunity for critical
      evaluation of study designs for industry-sponsored trials, independent of
      publication status. As part of a large public policy effort, the Clinical Trials
      Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov
      registry into a searchable dataset to facilitate research on clinical trials
      themselves. METHODS: We conducted a cross-sectional analysis of 477 HIV and HCV
      drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to
      27 September 2010, to study the relationship of study sponsorship with randomized
      study design. The likelihood of using randomization given industry (versus non
      industry) sponsorship was reported with prevalence ratios (PR). PRs were
      estimated using crude and stratified tabular analysis and Poisson regression
      adjusting for presence of a data monitoring committee, enrollment size, study
      phase, number of study sites, inclusion of foreign study sites, exclusion of
      persons older than age 65, and disease condition. RESULTS: The crude PR was 1.17
      (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82,
      1.56). There was a trend toward mild effect measure modification by study phase,
      but this was not statistically significant. In stratified tabular analysis the
      adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI
      0.50, 2.22) among phase 4 trials. CONCLUSIONS: No significant relationship was
      found between industry sponsorship and use of randomization in trial design in
      this cross-sectional study. Prospective studies evaluating other aspects of trial
      design may shed further light on the relationship between industry sponsorship
      and appropriate trial methodology.

PMID- 24450315
TI  - Streptococcal pharyngitis: guidelines, treatment issues, and sequelae.

PMID- 24450316
TI  - A 6-week-old boy with annular skin lesions. Neonatal lupus erythematosus.
AB  - A 6-week-old, otherwise healthy boy presented to the dermatology clinic for
      evaluation of an eruption involving his scalp, face, and trunk. The truncal
      lesions had been present for several weeks, and the facial and scalp lesions were
      noticed 5 days prior to presentation. The eruption was asymptomatic without
      scratching or discomfort noted by his mother. Past medical history was remarkable
      for preterm delivery due to maternal hypertension during pregnancy. The infant
      was thriving and gaining weight appropriately. There was no family history of
      cutaneous or autoimmune disease. No one in the family had a recent tinea
      infection. On physical exam, he was a well-appearing, vigorous infant. There were
      multiple erythematous papules and annular plaques involving his left pre
      auricular and post-auricular areas, scalp, upper chest, and right abdominal wall
      (Figures 1 and 2). No other cutaneous or mucus membrane lesions were noted. His
      cardiac, lung, and abdominal exams were normal.

PMID- 24450317
TI  - A 21-day-old boy with an annular eruption. Tinea faciei / Tinea capitis.
AB  - A healthy 21-day-old black male was referred to pediatric dermatology for
      evaluation of a facial and scalp eruption that had been present for less than 1
      week. The child's parents had applied a topical corticosteroid cream for several
      days without any improvement noted. The child was otherwise well and thriving.
      Review of systems was negative. Family history was unremarkable for autoimmune or
      infectious skin diseases. On physical examination the patient was alert, active,
      and vigorous. He had multiple 1 to 2.5-cm erythematous annular, scaly plaques
      with pustules on the periphery on his upper cheeks, forehead, and anterior scalp
      (Figures 1-2). No alopecia was noted. Occipital and neck lymph nodes were not
      palpable. A potassium hydroxide skin preparation was negative for fungal elements
      and a fungal culture was performed. Serum laboratory testing was also performed.

PMID- 24450318
TI  - Feasibility, reproducibility, and clinical validity of the pediatric anxiety
      rating scale-revised for fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common inherited cause of intellectual
      disability and the most common known genetic cause of autism. FXS is associated
      with psychiatric impairments, including anxiety disorders. There is a paucity of
      well-developed measures to characterize anxiety in FXS. However, such scales are
      needed to measure therapeutic responses to interventions. The Pediatric Anxiety
      Rating Scale-Revised (PARS-R) was evaluated in 49 individuals with FXS.
      Feasibility, reproducibility, and clinical validity were assessed. High inter
      rater, test-retest, and cross-site reliability were achieved. PARS-R scores were
      correlated with parent-report and physician ratings of anxiety, suggesting good
      clinical validity. Results were similar within gender and age subgroups. The PARS
      R is a promising tool for measuring the efficacy of interventions targeting
      anxiety in FXS.

PMID- 24450319
TI  - Effects of dose frequency of early communication intervention in young children
      with and without Down syndrome.
AB  - Children with intellectual disability were randomly assigned to receive Milieu
      Communication Teaching (MCT) at one 1-hr session per week (low dose frequency,
      LDF) or five 1-hr sessions per week (high dose frequency, HDF) over 9 months (
      Fey, Yoder, Warren, & Bredin-Oja, 2013 . Non-Down syndrome (NDS) and Down
      syndrome (DS) subgroups were matched on intelligence, mental age, and
      chronological age. The NDS group had significantly more growth in spoken
      vocabulary than the DS group. In the DS subgroup, the HDF group had more spoken
      vocabulary growth than the LDF group when IQ was controlled. In both etiological
      subgroups, the HDF group yielded greater vocabulary production outcomes than the
      LDF group for children who played functionally with a range of objects.

PMID- 24450320
TI  - Modeling family adaptation to fragile X syndrome.
AB  - Using data from a survey of 1,099 families who have a child with Fragile X
      syndrome, we examined adaptation across 7 dimensions of family life: parenting
      knowledge, social support, social life, financial impact, well-being, quality of
      life, and overall impact. Results illustrate that although families report a high
      quality of life, they struggle with areas such as social support, social life,
      and parenting knowledge. Path analysis revealed that child and family factors
      play a role in adaptation, but family resources and social supports moderated
      their effect on quality of life, well-being, and overall impact. The
      interrelationship among multiple aspects of family life should be examined to
      improve family resiliency.

PMID- 24450321
TI  - Adaptive behavior and problem behavior in young children with Williams syndrome.
AB  - The present study compares the adaptive behavior profile of 18 young children
      with Williams syndrome (WS) and a developmentally matched group of 19 children
      with developmental disabilities and examines the relationship between adaptive
      behavior and problem behaviors in WS. Parents completed the Vineland Adaptive
      Behavioral Scales-Interview edition and the Developmental Behavior Checklist
      Primary Caregiver version (WS only). Children with WS had higher adaptive
      communication scores than children with other developmental disabilities.
      Children with WS demonstrated relative strengths in adaptive communication and
      socialization, coupled with relative weaknesses in daily living. Adaptive
      communication and socialization were negatively associated with problem behaviors
      in social relating in WS.

PMID- 24450322
TI  - Employment outcomes of transition-aged adults with autism spectrum disorders: a
      state of the States report.
AB  - The primary purpose of this study was to evaluate the employment outcomes of
      transition-aged adults with autism spectrum disorders (ASD) served by vocational
      rehabilitation services (VR) over the last 10 years by state. A secondary purpose
      was to compare employment outcomes of individuals with ASD to those of the
      overall transition-aged population served by VR for the same time period.
      Although there was variability both within and among states, the results of this
      study indicate that, over time, the number of young adults with ASD seeking VR
      services has increased; however, employment outcomes including the percent of
      adults with ASD achieving employment, the number of hours worked, and wages
      earned have not improved for this group. The cost to provide VR services to
      transition-aged adults with ASD was relatively stable over time. Transition-aged
      adults with ASD were more likely to become successfully employed as a result of
      receiving VR services than the overall population of transition-aged adults
      served by VR. However, the employed transition-aged adults consistently worked
      fewer hours and earned lower wages than those in the overall population. Factors
      that may influence variability within and among states, and between groups, and
      implications for research and practice are discussed.

PMID- 24450323
TI  - Nonverbal and verbal cognitive discrepancy profiles in autism spectrum disorders:
      influence of age and gender.
AB  - Research suggests that discrepant cognitive abilities are more common in children
      with autism spectrum disorder (ASD) and may indicate an important ASD
      endophenotype. The current study examined the frequency of IQ discrepancy
      profiles (nonverbal IQ > verbal IQ [NVIQ > VIQ], verbal IQ > nonverbal IQ [VIQ >
      NVIQ], and no split) and the relationship of gender, age, and ASD symptomatology
      to IQ discrepancy profile in a large sample of children with ASD. The NVIQ > VIQ
      profile occurred at a higher frequency than expected, had more young males, and
      showed more autism symptoms than the other groups. Results suggest that the NVIQ
      > VIQ profile may be less likely to represent a subtype of ASD, but rather a
      common developmental pathway for children with ASD and other disorders.

PMID- 24450326
TI  - The potential to predict the course of childhood asthma.
AB  - Many children experience pre-school or early childhood wheezing. In a significant
      proportion symptoms disappear as the child grows, but others have persistent and
      troublesome asthma which can be life-long. Tools to predict course of disease in
      young children are a priority for families and clinicians. This review summarizes
      evidence from several longitudinal population-based birth-cohort studies that
      have identified risk factors for persistence and remission of childhood asthma.
      These factors include clinical characteristics, environmental and other
      exposures, familial factors, biomarkers of allergic inflammation, measurements of
      lung function and airway responsiveness, and genetic variants. This review also
      introduces the concept of polygenic risk and genetic risk scores, and describes
      results from a recent study that suggests promise for the use of genetic
      information in predicting the course of childhood asthma. We conclude with a
      discussion of implications and future directions. 

PMID- 24450327
TI  - Gallium-68 DOTATOC PET/CT in vivo characterization of somatostatin receptor
      expression in the prostate.
AB  - AIM: The aim was to investigate somatostatin receptor (sstr) expression in normal
      prostate by determining the maximum standardized uptake value (SUVmax) of (68)Ga
      DOTATOC PET/CT in neuroendocrine tumor (NET) patients, without NET involvement of
      the prostate gland, for establishing the reference standard. METHODS: Sixty-four
      NET patients underwent (68)Ga-DOTATOC PET/CT. SUVmax of the prostate gland,
      normal liver, testes, and gluteus muscles were evaluated. The prostate gland size
      was measured. Statistical analysis was performed using dedicated software
      (SPSS13). RESULTS: Mean/median (68)Ga-DOTATOC SUVmax values were as follows:
      normal prostate 2.6 +/- 0.0, slightly enlarged prostate 4.2 +/- 1.6, prostatic
      hypertrophy 4.9 +/- 1.6, prostatic hyperplasia 5.0 +/- 1.5, prostate cancer 9.5
      +/- 2.1, normal liver 7.3 +/- 1.8, testes 1.8 +/- 0.5, and gluteus 1.0 +/- 0.2.
      The normal prostate gland had three times less sstr expression than normal liver
      tissue. Strong correlation was found between patient age and sstr expression in
      prostate/prostate size. No significant difference existed in sstr expression
      between prostatic hypertrophy and hyperplasia. Much higher sstr expression was
      found in prostatic cancer compared with normal prostate. CONCLUSION: (68)Ga
      DOTATOC PET/CT defines the baseline sstr uptake in prostate not affected by NET
      (significantly lower than in the liver). Higher values were established in
      prostatic hyperplasia and hypertrophy. Only concomitant prostate cancer was
      associated with higher SUVmax in comparison with non-neoplastic liver.

PMID- 24450328
TI  - A new species of Spauligodon (Nematoda: Oxyuroidea: Pharyngodonidae) in
      Cyrtodactylus bintangrendah (Sauria: Gekkonidae) from Peninsular Malaysia.
AB  - Spauligodon bintangensis n. sp. from the intestines of Cyrtodactylus
      bintangrendah (Gekkonidae) from Peninsular Malaysia is described and illustrated.
      Spauligodon bintangensis n. sp. represents the 51st species assigned to the genus
      and the first species from the Oriental Region. The new species is most similar
      to Spauligodon atlanticus, Spauligodon eremiasi, and Spauligodon occidentalis,
      but is easily separated by position of vulva, prebulbar in S. atlanticus and S.
      occidentalis , postbulbar in the new species, and location of lateral alae; in S.
      eremiasi, the lateral alae occur only in the fourth quarter of the body, whereas
      in the new species the lateral alae begin just posterior to lips.

PMID- 24450331
TI  - Type I IFN signature in primary Sjogren's syndrome patients.
AB  - Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease characterized
      by lymphocytic infiltrates in salivary and lacrimal glands. Clinical
      manifestations range from ocular and oral dryness to vasculitis and severe
      fatigue. pSS is a disease with heterogeneous symptoms and a variable response to
      the available treatment. Recently, a key role for Interferon (IFN) type I has
      been implicated in the pathogenesis of pSS. As type I IFN consists of 17
      different subtypes, it cannot be easily assessed using a conventional ELISA.
      Therefore the expression of type I IFN inducible genes--the so-called type I IFN
      signature--is assessed in salivary gland tissue and blood from patients as a
      readout for type I IFN activity. In this review we discuss the potential of type
      I IFN as a novel biomarker for disease activity, subclassification of patients,
      prediction of therapy response and most importantly as a target for therapeutic
      intervention.

PMID- 24450332
TI  - Thirty years of JOPT.

PMID- 24450333
TI  - Eyes on new product development.

PMID- 24450334
TI  - Is there a moral obligation to conceive children under the best possible
      conditions? A preliminary framework for identifying the preconception
      responsibilities of potential parents.
AB  - BACKGROUND: The preventative paradigm of preconception care is receiving
      increasing attention, yet its boundaries remain vague in three respects:
      temporally; agentially; and instrumentally. Crucially, it remains unclear just
      who is to be considered a 'potential parent', how soon they should take up
      preconception responsibilities, and how weighty their responsibilities should be.
      DISCUSSION: In this paper, we argue that a normal potential parent of reasonable
      prudence has a moral duty to adequately optimize the conditions under which she
      or his reproductive partner will conceive, though a proportionality calculus
      calls for toleration of several forms of preconception behaviour that are non
      ideal from the perspective of reproductive risk. We distinguish between five
      categories of potential parents to which different duties of preconception care
      should be ascribed. This framework is advanced to assign preconception care
      responsibilities with more precision than is often done in the current debate on
      preconception care. We conclude by applying our theoretical framework to three
      types of preconception care interventions: consumption of folic acid; keeping
      one's weight under control; and engaging in preconception genetic screening. Our
      analysis shows that the literature on preconception care often glosses over
      crucial distinctions between different types of potential parents and uses a
      notion of preconception beneficence that may be overly demanding. Nevertheless,
      preconception moral duties will often be weighty and reluctance to accept such
      duties on account of the burden they impose do not warrant preconception
      insouciance. SUMMARY: To avoid misplaced responsibility ascriptions in the
      growing field of preconception care, distinctions must be made between different
      types of potential parents to whom different degrees of preconception
      responsibility apply. We present such a preliminary framework and bring it to
      bear on the cases of folic acid consumption, obesity and genetic testing.

PMID- 24450335
TI  - Comparative evaluation of the indigenous microbial diversity vs. drilling fluid
      contaminants in the NEEM Greenland ice core.
AB  - Demonstrating that the detected microbial diversity in nonaseptically drilled
      deep ice cores is truly indigenous is challenging because of potential
      contamination with exogenous microbial cells. The NEEM Greenland ice core project
      provided a first-time opportunity to determine the origin and extent of
      contamination throughout drilling. We performed multiple parallel cultivation and
      culture-independent analyses of five decontaminated ice core samples from
      different depths (100-2051 m), the drilling fluid and its components Estisol and
      Coasol, and the drilling chips collected during drilling. We created a collection
      of diverse bacterial and fungal isolates (84 from the drilling fluid and its
      components, 45 from decontaminated ice, and 66 from drilling chips). Their
      categorization as contaminants or intrinsic glacial ice microorganisms was based
      on several criteria, including phylogenetic analyses, genomic fingerprinting,
      phenotypic characteristics, and presence in drilling fluid, chips, and/or ice.
      Firmicutes and fungi comprised the dominant group of contaminants among isolates
      and cloned rRNA genes. Conversely, most Proteobacteria and Actinobacteria
      originating from the ice were identified as intrinsic. This study provides a
      database of potential contaminants useful for future studies of NEEM cores and
      can contribute toward developing standardized protocols for contamination
      detection and ensuring the authenticity of the microbial diversity in deep
      glacial ice.

PMID- 24450336
TI  - A comparison of the responsible drinking dimensions among underage and legal
      drinkers: examining differences in beliefs, motives, self-efficacy, barriers and
      intentions.
AB  - BACKGROUND: To date, scholarly discourse over the Amethyst Initiative has
      primarily debated the relative effectiveness of the 21 year-old Minimum Legal
      Drinking Age (MLDA). Unfortunately, this discourse has failed to account for the
      Amethyst Initiative's central tenet/mission: facilitating responsible drinking
      among college students. This investigation seeks to help fill this gap by
      quantitatively determining whether a random sample of underage (n = 158) and
      legal (n = 298) drinkers differed with regard to their alcohol-related behaviors,
      responsible drinking behaviors, and responsible drinking beliefs. FINDINGS:
      Compared to legal drinkers, underage drinkers reported: (a) significantly less
      confidence to perform responsible drinking behaviors during their next drinking
      episode [t(446) = -2.97, p < .003; d = -0.297], (b) significantly more perceived
      barriers to responsible drinking [t(388) = 3.44, p < .001; d = .368], and (c)
      significantly lower behavioral intentions to perform responsible drinking
      behaviors the next time they consumed alcohol [t(437) = -3.45, p < .001; d = 
      0.350]. Each of these differences remained statistically significant, even after
      controlling for sex and race, in three separate multiple linear regression
      models. CONCLUSION: While college students both above and below the 21 year-old
      MLDA have similar beliefs regarding what constitutes responsible drinking,
      students below the current MLDA have less intention to drink responsibly
      regardless of their behavioral beliefs and/or motives. College/university
      administrators should consider the negative repercussions that are possible if
      underage students who are less confident in their ability to drink responsibly
      are given the legal right to drink on campus.

PMID- 24450338
TI  - Acidifying and yeast extract in diets for adults cats.
AB  - This study evaluated the effects of adding an acidifying agent based on
      phosphoric acid (A), a yeast extract from a specific strain (Saccharomyces
      cerevisiae) (Y) and the combination of these two additives in food for adult
      cats. A test was conducted with 24 animals (mean 3.5 years old), mixed breed,
      weighing 3.72 +/- 0.74 kg, kept in individual metabolic cages and distributed in
      a completely randomized design with a 2 * 2 factorial design (with or without A
      0.6% of dry matter, with or without Y 1.5% of dry matter) totalling four
      treatments and six replicates of each condition. The experimental period was 15
      days. The A or the Y reduced (P< 0.01) the dry matter intake, but the effect was
      not observed when they were associated. The association improved (P<0.05) the
      digestibility of dry matter and ashes. The A reduced urine pH (P=0.05) regardless
      of the presence of the Y. There was no effect (P>0.09) on other parameters
      evaluated. Results of this study show that the isolated use of 0.6% A or 1.5% Y
      in diets for cats is not recommended. However, the association of these two
      additives was beneficial in increasing nutrient digestibility.

PMID- 24450339
TI  - Impact of myocardial reperfusion status on QT dispersion after successful
      recanalization of the infarct-related artery in acute myocardial infarction.
AB  - OBJECTIVE: To determine whether adequate myocardial perfusion status after
      transluminal recanalization is associated with prompt improvement of QT
      dispersion (QTd). BACKGROUND: Transluminal recanalization of the infarct-related
      coronary artery in acute myocardial infarction aims to promptly restore
      myocardial perfusion, to maximize electrical and mechanical recovery. QTd
      represents the heterogeneity of ventricular repolarization, which may affect
      electrical stability. METHODS: Forty patients who underwent primary percutaneous
      coronary intervention for their first anterior acute ST-elevation myocardial
      infarction were prospectively enrolled. Myocardial reperfusion status was
      assessed by myocardial blush grade (MBG) on the final angiogram after successful
      recanalization (Thrombolysis In Myocardial Infarction Grade 3 flow). RESULTS:
      Preprocedural QTd was similar in patients with final MBG 0-1, 2, and 3 (76 +/-
      24, 67 +/- 13, and 69 +/- 13 milliseconds, respectively; P = 0.661). After
      recanalization, QTd decreased in patients with MBG 3 (39 +/- 16 milliseconds, P <
      0.001) but not in patients with MBG 0-1 (74 +/- 20 milliseconds) or MBG 2 (82 +/-
      16 milliseconds). Multivariate analysis showed that postprocedural MBG was an
      independent predictor of QTd after recanalization (standardized regression
      coefficient = -0.628, P < 0.001). CONCLUSIONS: Adequate tissue perfusion may be
      crucial for electrical stability of the myocardium after reperfusion.

PMID- 24450337
TI  - 4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine
      1-carbothioamide (ML267), a potent inhibitor of bacterial phosphopantetheinyl
      transferase that attenuates secondary metabolism and thwarts bacterial growth.
AB  - 4'-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational
      modification essential to bacterial cell viability and virulence. We present the
      discovery and medicinal chemistry optimization of 2-pyridinyl-N-(4
      aryl)piperazine-1-carbothioamides, which exhibit submicromolar inhibition of
      bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover,
      compounds within this class possess antibacterial activity in the absence of a
      rapid cytotoxic response in human cells. An advanced analogue of this series,
      ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent
      metabolite when applied to Bacillus subtilis at sublethal doses. Additional
      testing revealed antibacterial activity against methicillin-resistant
      Staphylococcus aureus , and chemical genetic studies implicated efflux as a
      mechanism for resistance in Escherichia coli . Additionally, we highlight the in
      vitro absorption, distribution, metabolism, and excretion and in vivo
      pharmacokinetic profiles of compound 55 to further demonstrate the potential
      utility of this small-molecule inhibitor. 

PMID- 24450341
TI  - Advances in laparoscopic colorectal surgery.

PMID- 24450342
TI  - Evaluation of pain scores after single-incision and conventional laparoscopic
      cholecystectomy: a randomized control trial in a rural Indian population.
AB  - INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) is considered
      to be less invasive and have less morbidity than conventional laparoscopic
      cholecystectomy (CLC). However, there is a relative paucity of data regarding
      postoperative pain scores in rural Indian populations following SILC. Also, data
      pertaining to the applicability of SILC in rural Indian population are scant.
      METHODS: In the present randomized control trial, pain scores after SILC and CLC
      were evaluated. Sixty patients with gallstone disease were randomly assigned to
      one of two groups with 30 patients each: the CLC group and the SILC group.
      Postoperative pain scores were recorded on the visual analog scale at 8 hours, 24
      hours and 7 days after surgery. RESULTS: The patients were comparable with
      respect to age, sex and BMI. Operative time was longer for the SILC group (47.73
      +/- 5.57 min vs 69.53 +/- 8.96 min; P < 0.0001).The pain scores were similar in
      both groups at 8 hours (3.61 +/- 0.41 vs 3.50 +/- 0.51; P = 0.36) and 24 hours
      (3.30 +/- 0.59 vs 3.20 +/- 0.40; P = 0.44) postoperatively. On day 7, the SILC
      group had lower pain scores than the CLC group (2.56 +/- 0.56 vs 1.16 +/- 0.37; P
      < 0.01). CONCLUSION: There was no distinct advantage to SILC with regard to
      immediate postoperative pain. Pain was significantly less (P < 0.01) in the SILC
      group on postoperative day 7.

PMID- 24450340
TI  - Cruentaren A binds F1F0 ATP synthase to modulate the Hsp90 protein folding
      machinery.
AB  - The molecular chaperone Hsp90 requires the assistance of immunophilins, co
      chaperones, and partner proteins for the conformational maturation of client
      proteins. Hsp90 inhibition represents a promising anticancer strategy due to the
      dependence of numerous oncogenic signaling pathways upon Hsp90 function.
      Historically, small molecules have been designed to inhibit ATPase activity at
      the Hsp90 N-terminus; however, these molecules also induce the pro-survival heat
      shock response (HSR). Therefore, inhibitors that exhibit alternative mechanisms
      of action that do not elicit the HSR are actively sought. Small molecules that
      disrupt Hsp90-co-chaperone interactions can destabilize the Hsp90 complex without
      induction of the HSR, which leads to inhibition of cell proliferation. In this
      article, selective inhibition of F1F0 ATP synthase by cruentaren A was shown to
      disrupt the Hsp90-F1F0 ATP synthase interaction and result in client protein
      degradation without induction of the HSR. 

PMID- 24450343
TI  - Laparoscopic management of hypertrophic hypersecretory gastropathy with protein
      loss: a case report.
AB  - Hypertrophic hypersecretory gastropathy with protein loss (HHGP) is a rare form
      of acquired gastropathy characterized by giant gastric rugal folds and
      hypoalbuminemia. It is often misdiagnosed as Menetrier's disease. We report the
      case of a 45-year-old man with HHGP who presented with nausea and anorexia. The
      patient had no underlying disease and was not on medication.
      Esophagogastroduodenoscopy and CT showed a thickening of the gastric folds in the
      stomach. As cancer cells were not detected on endoscopic biopsies, the patient
      was diagnosed with Menetrier's disease. He was managed with a high-protein diet
      and annual follow-up by esophagogastroduodenoscopy. Five years after the
      diagnosis, the patient underwent laparoscopy-assisted total gastrectomy for
      refractory abdominal pain, diarrhea, and protein loss. A pathological diagnosis
      of HHGP was made and he was discharged without any surgical complications. The
      patient was relieved of anorexia, abdominal pain, and diarrhea. Laparoscopy
      assisted total gastrectomy could be regarded as a treatment option for HHGP. 

PMID- 24450344
TI  - Laparoscopic abdominosacral resection for locally advanced primary rectal cancer
      after treatment with mFOLFOX6 plus bevacizumab, followed by preoperative
      chemoradiotherapy.
AB  - Abdominosacral resection may be the only curative procedure for locally advanced
      rectal cancer involving the presacral fascia or sacrum. Multimodal therapy might
      be necessary to prevent local and distant recurrence for such tumors. A 67-year
      old man was diagnosed with locally advanced rectal cancer widely involving the
      right pelvic sidewall and presacral fascia near the S4/5 junction on the right
      posterolateral side. We performed laparoscopic abdominosacral resection (S4/5)
      with en bloc right lateral lymph node dissection and seminal vesicle resection to
      obtain a clear resection margin after systemic chemotherapy with mFOLFOX6
      (oxaliplatin, leucovorin, and 5-fluorouracil) plus bevacizumab, followed by
      preoperative chemoradiotherapy. The total operative time was 660 min, and the
      estimated blood loss was 550 mL. The final pathological findings revealed no
      residual cancer cells (pathological complete response). Laparoscopic
      abdominosacral resection appears to be safe and feasible in selected patients. 

PMID- 24450345
TI  - Rectal arteriovenous fistula resected laparoscopically after laparoscopic
      sigmoidectomy: a case report.
AB  - We report a very rare case of rectal arteriovenous fistula following
      sigmoidectomy and discuss this case in the context of the existing literature. In
      April 2011, the patient, a man in his 60s, underwent laparoscopic sigmoidectomy
      with lymph node dissection for sigmoid colon cancer. Beginning in February 2012,
      he experienced frequent diarrhea. Abdominal contrast-enhanced CT revealed local
      thickening of the rectal wall and rectal arteriovenous fistula near the
      anastomosis site. Rectitis from the rectal arteriovenous fistula was diagnosed.
      No improvement was seen with conservative treatment. Therefore, surgical
      resection was performed laparoscopically and the site of the lesion was confirmed
      by intraoperative angiography. The arteriovenous fistula was identified and
      resected. Postoperatively, diarrhea symptoms resolved, and improvement in rectal
      wall thickening was seen on abdominal CT. No recurrence has been seen as of 1
      year postoperatively. 

PMID- 24450346
TI  - Hepatectomy for liver abscess caused by stones spilled during laparoscopic
      cholecystectomy.
AB  - An abdominal abscess caused by spilled stones is a serious complication of
      laparoscopic cholecystectomy that requires drainage or reoperation to remove the
      scattered stones. Herein, we report the case of a 50-year-old woman, who was on
      dialysis for renal failure. She underwent major hepatectomy for a liver abscess
      caused by stones spilled during laparoscopic cholecystectomy. 

PMID- 24450347
TI  - Single-incision laparoscopic hepatic resection in patients with previous hepatic
      resections: a mini case series.
AB  - Single-incision laparoscopic hepatic resection has been attracting increased
      attention from the surgical community in recent years. While there have been
      reports and studies on this procedure, none has suggested the possibility of
      doing repeated hepatic resections via a single incision. This report on three
      such cases aims to determine the feasibility and safety of this approach for such
      patients. Three patients who had previously had liver resections underwent single
      incision laparoscopic hepatic resection in our center. Patient demographics, type
      of port and instruments used, operating time, complications and incision length
      were collected. The operating time in each case was less than 230 min. The
      incision length for the single-port device was 3.5 cm or less. The length of
      hospital stay was less than 5 days in each case. Intra-operative blood loss was
      limited to 250 mL in each case. There were no immediate postoperative
      complications related to hepatic resection. Single-incision laparoscopic hepatic
      resection is feasible for selected patients who have had previous hepatic
      resections. Because the port entry site for the single-incision laparoscopic
      approach is usually slightly larger than that for the conventional approach, it
      is safer in re-resection cases where there may be adhesions from previous
      surgery. Other possible benefits, such as cosmesis and reduced port-associated
      morbidity, are mainly related to the use of only one small incision. 

PMID- 24450348
TI  - Laparoendoscopic approach for refractory Roux-en-Y hepaticojejunostomy stricture
      in an acute setting: a unique case and technique.
AB  - Roux-en-Y hepaticojejunostomy stricture is a substantial problem that develops in
      10%-30% of patients and requires frequent intervention. Although
      endoscopic/percutaneous approaches are preferred, especially for refractory
      stricture, open surgical reconstruction remains the gold standard. However, such
      an operation may be highly challenging. The recently developed covered, self
      expanding metallic stent is a useful option for such difficult cases. We present
      a case of recurrent Roux-en-Y hepaticojejunostomy stricture complicated by
      densely packed intrahepatic stones and suppurative cholangitis with failed
      percutaneous biliary draining. Enteroscopic manipulations were unfeasible, and
      the case was successfully managed by the laparoendoscopic approach. If treating
      surgeons have the necessary expertise, this technique may be considered in such
      difficult scenarios. 

PMID- 24450349
TI  - Laparoscopic total remnant pancreatectomy after laparoscopic
      pancreaticoduodenectomy.
AB  - Total remnant pancreatectomy after pancreaticoduodenectomy (PD) is a difficult
      procedure. Recently, distal pancreatectomy and PD have been performed
      laparoscopically. Herein, we present the first case report of a laparoscopic
      total remnant pancreatectomy. A 72-year-old woman underwent a totally
      laparoscopic pylorus-preserving PD for inferior bile duct cancer. The tumor was
      composed of moderately differentiated tubular adenocarcinoma and was diagnosed as
      pStage III according to the UICC-TNM classification. Eighteen months later, CT
      showed a low-density mass in the remnant pancreas. We conducted a total resection
      of the remnant pancreas laparoscopically. Histologically, it was diagnosed as a
      primary pancreatic cancer. The patient's postoperative course was uneventful. She
      was discharged on postoperative day 14. When an initial PD is performed
      laparoscopically, laparoscopic total remnant pancreatectomy is technically
      feasible and safe in selected patients. 

PMID- 24450350
TI  - Pancreatoduodenal artery aneurysm resulting from median arcuate ligament
      compression successfully treated with laparoscopic ligament section.
AB  - True aneurysms of the pancreatoduodenal arteries are frequently associated with
      stenosis or occlusion of the celiac trunk caused by median arcuate ligament
      compression. Celiac stenosis cannot be cured, even by transarterial embolization,
      which has recently become a good alternative to open surgical repair. To prevent
      recurrence, management of median arcuate ligament compression to correct
      hemodynamics in vascular networks should also be performed. Herein we report a
      case of pancreatoduodenal arterial aneurysm with median arcuate ligament
      compression that was successfully treated with minimally invasive laparoscopic
      median arcuate ligament section. The patient was discharged 4 days after surgery
      with no complications. Enhanced CT 1 month after surgery revealed no residual
      celiac trunk stenosis or aneurysm. Normalization of blood flow by laparoscopic
      median arcuate ligament section is a good option for some patients with a
      pancreatoduodenal arterial aneurysm. 

PMID- 24450351
TI  - Successful thoracoscopic removal of a giant teratoma following extraction of
      cystic conponents: a case report.
AB  - Video-assisted thoracoscopic surgery is a type of minimal-access surgery. The
      nature of the surgery means that there are limitations on the size of a tumor
      that can be removed through an access incision. Herein, we report our experience
      removing a giant teratoma (16 * 14 * 13 cm in size) from the anterior mediastinum
      of a young girl. We employed video-assisted thoracoscopic surgery to remove the
      teratoma through a mini-thoracotomy following the extraction of the cystic
      components. 

PMID- 24450352
TI  - Thoracoscopic management of cervical thoracic duct injuries after thyroidectomy
      with lymphadenectomy.
AB  - We present a case of postoperative cervical chylous fistula after neck dissection
      of advanced thyroid carcinoma that was managed successfully by thoracoscopic
      ligation of the thoracic duct. A double lumen endobronchial tube was introduced
      for selective single-lung ventilation with the patient under general anesthesia.
      The patient was placed in the left decubitus position. Four thoracoports were
      introduced in the collapsed right lung. The thoracic duct was ligated at two
      points, and two clips were applied. Postoperatively, neck drainage ceased
      immediately. The chest tube and closed neck drains were removed on postoperative
      days 2 and 8, respectively. The patient was discharged on postoperative day 9.
      Thoracoscopy is a safe and effective treatment of chylous fistula in the neck.
      Compared to the open procedure, the minimally invasive thoracoscopic approach
      causes less pain and fosters faster rehabilitation and recovery. 

PMID- 24450353
TI  - Natural orifice specimen extraction using prolapsing technique in single-incision
      laparoscopic colorectal resections for colorectal cancers.
AB  - INTRODUCTION: It is often technically difficult to cut the lower rectum with an
      endoscopic linear stapler in single-incision laparoscopic colorectal resections
      (SILC) because some surgical devices are inserted through the same access
      platform. If the rectum is cut incorrectly, it may cause anastomotic leakage. We
      recently applied natural orifice specimen extraction (NOSE) using the prolapsing
      technique to overcome this technical difficulty in SILC procedures in selected
      patients. MATERIALS AND SURGICAL TECHNIQUE: The access platform is placed in the
      small umbilical incision area. SILC is performed using a surgical technique
      similar to the conventional laparoscopic medial-to-lateral approach. The proximal
      part of the tumor site is transected with laparoscopic staplers. Then, the tumor
      lesion and bowel are pulled out of the body through the anus by means of
      inversion. Next, the distal side of the bowel is cut with a stapler and the
      rectal stump is reinforced with sutures under direct vision. The distal side of
      the bowel is then pushed back into the body. NOSE with prolapsing technique is
      then complete. After that, the anvil is attached to the proximal part of the
      bowel at the umbilical incision site, and intracorporeal anastomosis is
      performed. DISCUSSION: NOSE with prolapsing technique was applied in 14 SILC
      procedures for colorectal cancer patients. All procedures were successful, and
      there were no anastomotic leakages in the series. This technique enabled us to
      perform pure SILC safely without affecting cosmesis, even in cases where we
      needed to cut the lower rectum.

PMID- 24450354
TI  - Extraperitoneal colostomy in laparoscopic abdominoperineal resection using a hand
      inserted from the perineal side.
AB  - INTRODUCTION: Extraperitoneal colostomy is considered to be more effective at
      preventing post-colostomy complications than intraperitoneal colostomy. However,
      this operation is difficult via laparoscopic surgery alone. We present an
      extraperitoneal colostomy technique using a hand inserted from the perineal side.
      MATERIALS AND SURGICAL TECHNIQUE: Extraperitoneal colostomy was performed in five
      patients. After the rectum was resected, a hand was inserted into the abdominal
      cavity from the perineal side, and pneumoperitoneum was created. The peritoneum
      was dissected to make the extraperitoneal route, and the proximal colon was
      passed along this route with fingers and laparoscopic manipulation. All
      procedures were completed without tissue damage or hemorrhage. No patient
      developed a hernia or ileus postoperatively. DISCUSSION: Laparoscopic
      abdominoperineal resection for an extraperitoneal colostomy is difficult via
      laparoscopic ports only. It can be simplified by operating with manual assistance
      via the perineal wound.

PMID- 24450355
TI  - Bouveret's syndrome: a rare cause of abdominal pain in the elderly.

PMID- 24450356
TI  - Diagnostic yield of endoscopic retrograde cholangiopancreatography-based cytology
      for distinguishing malignant and benign intraductal papillary mucinous neoplasm:
      systematic review and meta-analysis.
AB  - BACKGROUND AND AIM: Published studies have revealed the diagnostic yield of
      cytology obtained from endoscopic retrograde cholangiopancreatography (ERCP) in
      distinguishing malignant and benign intraductal papillary mucinous neoplasm
      (IPMN). However as a result of small sample sizes, the overall magnitude of
      benefit is unknown. Additionally, the optimal endoscopic procedure for cytology
      acquisition is also unclear. The aim of the present study was to evaluate the
      diagnostic yield of ERCP-based cytology in patients with IPMN and clarify the
      optimal sampling technique. METHODS: Relevant studies with a reference standard
      of definitive surgical histology were identified via MEDLINE and SCOPUS.
      Malignant IPMN included invasive adenocarcinoma, carcinoma in situ, and high
      grade dysplasia. For ERCP, studies using aspiration, brush, and lavage cytology
      were included. The main objective was the diagnostic yield (pooled sensitivity,
      specificity, positive likelihood ratio, negative likelihood ratio) of cytology
      obtained from ERCP to distinguish malignant and benign IPMN. RESULTS: Meta
      analysis of 13 international studies with 483 IPMN patients was conducted. Pooled
      sensitivity was 35.1%, specificity 97.2%, and accuracy 92.9%. Among the three
      ERCP techniques, lavage cytology showed the best diagnostic ability (sensitivity
      45.8%, specificity 97.9%). Malignant IPMN were observed in 45.1% (218/483) of
      patients in ERCP studies. CONCLUSIONS: Cytology from ERCP has good specificity
      but poor sensitivity in distinguishing benign from malignant IPMN. Newer
      techniques or markers are needed to improve diagnostic yield.

PMID- 24450357
TI  - Inter-pregnancy weight change impacts placental weight and is associated with the
      risk of adverse pregnancy outcomes in the second pregnancy.
AB  - BACKGROUND: The inter-pregnancy period is considered a teachable moment when
      women are receptive to weight- management guidance aimed at optimising pregnancy
      outcome in subsequent pregnancies. In population based studies inter-pregnancy
      weight change is associated with several adverse pregnancy outcomes but the
      impact on placental size is unknown. METHODS: The association between inter
      pregnancy weight change and the primary risk of adverse pregnancy outcomes in the
      second pregnancy was investigated in 12,740 women with first two consecutive
      deliveries at a single hospital using logistic regression. RESULTS: Compared with
      women who were weight stable, weight loss (>1BMI unit) between pregnancies was
      associated with an increased risk of spontaneous preterm delivery, low placental
      weight and small for gestational age (SGA) birth, while weight gain (>3BMI units)
      increased the risk of pre-eclampsia, gestational hypertension, emergency
      caesarean section, placental oversize and large for gestational age (LGA) birth
      at the second pregnancy. The relationship between weight gain and pre-eclampsia
      risk was evident in women who were overweight at first pregnancy only (BMI >=25
      units), while that between weight loss and preterm delivery was confined to women
      with a healthy weight at first pregnancy (BMI <25 units). In contrast, the
      association between weight loss and SGA was independent of first pregnancy BMI. A
      higher percentage of women who were obese at first pregnancy were likely to
      experience a large weight gain (P < 0.01) or weight loss (P < 0.001) between
      consecutive pregnancies compared with the normal BMI reference group. CONCLUSION:
      Inter-pregnancy weight change in either direction increases the risk of a number
      of contrasting pregnancy complications, including extremes of placental weight.
      The placenta may lie on the causal pathway between BMI change and the risk of LGA
      or SGA birth.

PMID- 24450358
TI  - A case report of hearing loss post use of hydroxychloroquine in a HIV-infected
      patient.
AB  - OBJECTIVE: A case with reversible symmetrical sensorineural hearing loss
      following hydroxychloroquine therapy is described. CASE SUMMARY: A 57-year-old,
      human immunodeficiency virus (HIV) positive man was referred to the HIV clinic of
      Imam Khomeini Hospital, Tehran with chief complaint of bilateral slowly
      progressive hearing loss starting from two months ago. The man had history of
      rheumatoid arthritis diagnosed from 3 months ago and was administered
      hydroxychloroquine 200 mg and prednisolone 5 mg twice daily. Audiometry test
      showed moderate to severe neuronal hearing loss and reduced speech recognition in
      both ears of the patient. With suspicion of hydroxychloroquine-induced hearing
      loss, this drug was discontinued. After 2 months of hydroxychloroquine
      discontinuation, his audiometry findings were improved. DISCUSSION: A few cases
      of hydroxychloroquine-induced hearing loss have been reported. All of the cases
      were non-HIV positive individuals. Irreversible hearing loss was developed
      following long-term therapy with hydroxychloroquine. The present case was a HIV
      positive man who developed hearing loss following short course (one month)
      hydroxychloroquine therapy and his problem was resolved following discontinuation
      of hydroxychloroquine and continuation of prednisolone. CONCLUSIONS:
      Hydroxychloroquine-induced hearing loss may reversibly occur following short term
      therapy in HIV patients.

PMID- 24450361
TI  - Mechanism of O2 activation and methanol production by (di(2
      pyridyl)methanesulfonate)Pt(II)Me(OH(n))((2-n)-) complex from theory with
      validation from experiment.
AB  - The mechanism of the (dpms)Pt(II)Me(OH(n))((2-n)-) oxidation in water to form
      (dpms)Pt(IV)Me(OH)2 and (dpms)Pt(IV)Me2(OH) complexes was analyzed using DFT
      calculations. At pH < 10, (dpms)Pt(II)Me(OH(n))((2-n)-) reacts with O2 to form a
      methyl Pt(IV)-OOH species with the methyl group trans to the pyridine nitrogen,
      which then reacts with (dpms)Pt(II)Me(OH(n))((2-n)-) to form 2 equiv of
      (dpms)Pt(IV)Me(OH)2, the major oxidation product. Both the O2 activation and the
      O-O bond cleavage are pH dependent. At higher pH, O-O cleavage is inhibited
      whereas the Pt-to-Pt methyl transfer is not slowed down, so making the latter
      reaction predominant at pH > 12. The pH-independent Pt-to-Pt methyl transfer
      involves the isomeric methyl Pt(IV)-OOH species with the methyl group trans to
      the sulfonate. This methyl Pt(IV)-OOH complex is more stable and more reactive in
      the Pt-to-Pt methyl-transfer reaction as compared to its isomer with the methyl
      group trans to the pyridine nitrogen. A similar structure-reactivity relationship
      is also observed for the S(N)2 functionalization to form methanol by two isomeric
      (dpms)Pt(IV)Me(OH)2 complexes, one featuring the methyl ligand trans to the
      sulfonate group and another with the methyl trans to the pyridine nitrogen. The
      barrier to functionalize the former isomer with the CH3 group trans to the
      sulfonate group is 2-9 kcal/mol lower. The possibility of the involvement of
      Pt(III) species in the reactions studied was found to correspond to high-barrier
      reactions and is hence not viable. It is concluded that the dpms ligand
      facilitates Pt(II) oxidation both enthalpically and entropically.

PMID- 24450359
TI  - Adaptor protein2 (AP2) orchestrates CXCR2-mediated cell migration.
AB  - The chemokine receptor CXCR2 is vital for inflammation, wound healing,
      angiogenesis, cancer progression and metastasis. Adaptor protein 2 (AP2), a
      clathrin binding heterotetrameric protein comprised of alpha, beta2, MU2 and
      sigma2 subunits, facilitates clathrin-mediated endocytosis. Mutation of the LLKIL
      motif in the CXCR2 carboxyl-terminal domain (CTD) results in loss of AP2 binding
      to the receptor and loss of ligand-mediated receptor internalization and
      chemotaxis. AP2 knockdown also results in diminished ligand-mediated CXCR2
      internalization, polarization and chemotaxis. Using knockdown/rescue approaches
      with AP2-MU2 mutants, the binding domains were characterized in reference to
      CXCR2 internalization and chemotaxis. When in an open conformation, MU2 Patch 1
      and Patch 2 domains bind tightly to membrane PIP2 phospholipids. When AP2-MU2, is
      replaced with MU2 mutated in Patch 1 and/or Patch 2 domains, ligand-mediated
      receptor binding and internalization are not lost. However, chemotaxis requires
      AP2-MU2 Patch 1, but not Patch 2. AP2-sigma2 has been demonstrated to bind
      dileucine motifs to facilitate internalization. Expression of AP2-sigma2 V88D and
      V98S dominant negative mutants resulted in loss of CXCR2 mediated chemotaxis.
      Thus, AP2 binding to both membrane phosphatidylinositol phospholipids and
      dileucine motifs is crucial for directional migration or chemotaxis. Moreover,
      AP2-mediated receptor internalization can be dissociated from AP2-mediated
      chemotaxis. 

PMID- 24450360
TI  - Morphology, morphogenesis, and molecular phylogeny of Paraparentocirrus
      sibillinensis n. gen., n. sp., a "Stylonychine Oxytrichidae" (Ciliophora,
      Hypotrichida) without transverse cirri.
AB  - A terrestrial oxytrichid ciliate Paraparentocirrus sibillinensis n. gen., n. sp.,
      which was found in soil samples of a beech forest stand within the National Park
      of Sibillini Mountains, Italy, was investigated using live observation and
      protargol impregnation. The morphology of interphase, morphogenesis, and
      molecular phylogeny inferred from SSU rDNA sequences of this ciliate were
      studied. Paraparentocirrus n. gen., is mainly characterized by a semirigid body,
      an undulating membrane in the Oxytricha pattern, six fronto-ventral (FV) rows,
      the absence of transverse cirri, one right and one left row of marginal cirri,
      four dorsal kineties, two dorsomarginal rows, and caudal cirri at the end of
      dorsal kinety 4. During morphogenesis, oral primordia develop through the
      proliferation of basal bodies from some cirri of FV rows 4 and 5, and FV row 6
      takes part in the anlagen formation of the proter. The dorsal morphogenesis was
      typical of oxytrichids, with simple fragmentation of dorsal kinety 3, and the
      dorsomarginal rows developed from the right marginal row. Phylogenetic analyses
      based on the SSU rDNA sequences support the classification of this new genus in
      the stylonychines. 

PMID- 24450362
TI  - Hepatitis C virus infection in patients with HIV-1: epidemiology, natural history
      and management.
AB  - Hepatitis C virus (HCV)-related liver diseases have contributed to increased
      morbidity and mortality in HIV-1-infected individuals in the era of effective
      antiretroviral therapy. HCV transmission patterns have changed among the HIV co
      infected population during the last decade, with acute HCV infection emerging
      worldwide. HIV infection accelerates the progression of HCV-related liver
      diseases and consequently cirrhosis, liver failure, and hepatocellular carcinoma.
      However, the current standard treatment of HCV infection with pegylated
      interferon plus ribavirin results in only a limited viral response. Furthermore,
      cumbersome pill regimens, antiretroviral related hepatotoxicity, and drug
      interactions of HCV and HIV regimens complicate therapy strategies. Fortunately,
      in the near future, new direct-acting anti-HCV agents will widen therapeutic
      options for HCV/HIV co-infection. Liver transplantation is also gradually
      accepted as a therapeutic option for end stage liver disease of HCV/HIV co
      infected patients. 

PMID- 24450363
TI  - Herbarium specimens reveal a historical shift in phylogeographic structure of
      common ragweed during native range disturbance.
AB  - Invasive plants provide ample opportunity to study evolutionary shifts that occur
      after introduction to novel environments. However, although genetic characters
      pre-dating introduction can be important determinants of later success, large
      scale investigations of historical genetic structure have not been feasible.
      Common ragweed (Ambrosia artemisiifolia L.) is an invasive weed native to North
      America that is known for its allergenic pollen. Palynological records from
      sediment cores indicate that this species was uncommon before European
      colonization of North America, and ragweed populations expanded rapidly as
      settlers deforested the landscape on a massive scale, later becoming an
      aggressive invasive with populations established globally. Towards a direct
      comparison of genetic structure now and during intense anthropogenic disturbance
      of the late 19th century, we sampled 45 natural populations of common ragweed
      across its native range as well as historical herbarium specimens collected up to
      140 years ago. Bayesian clustering analyses of 453 modern and 473 historical
      samples genotyped at three chloroplast spacer regions and six nuclear
      microsatellite loci reveal that historical ragweed's spatial genetic structure
      mirrors both the palaeo-record of Ambrosia pollen deposition and the historical
      pattern of agricultural density across the landscape. Furthermore, for unknown
      reasons, this spatial genetic pattern has changed substantially in the
      intervening years. Following on previous work relating morphology and genetic
      expression between plants collected from eastern North America and Western
      Europe, we speculate that the cluster associated with humans' rapid
      transformation of the landscape is a likely source of these aggressive invasive
      populations.

PMID- 24450364
TI  - Evidence of localized resource depletion following a natural colonization event
      by a large marine predator.
AB  - For central place foragers, forming colonies can lead to extensive competition
      for prey around breeding areas and a zone of local prey depletion. As populations
      grow, this area of reduced prey can expand impacting foraging success and forcing
      animals to alter foraging behaviour. Here, we examine a population of marine
      predators, the northern fur seal (Callorhinus ursinus), which colonized a
      recently formed volcanic island, and assess changes in foraging behaviour
      associated with increasing population density. Specifically, we measured pup
      production and adult foraging behaviour over a 15-year period, during which the
      population increased 4-fold. Using measures of at-sea movements and dive
      behaviour, we found clear evidence that as the population expanded, animals were
      required to allot increasing effort to obtain resources. These changes in
      behaviour included longer duration foraging trips, farther distances travelled, a
      larger foraging range surrounding the island and deeper maximum dives. Our
      results suggest that as the northern fur seal population increased, local prey
      resources were depleted as a result of increased intraspecific competition. In
      addition, the recent slowing of population growth indicates that this population
      may be approaching carrying capacity just 31 years after a natural colonization
      event. Our study offers insight into the dynamics of population growth and
      impacts of increasing population density on a large marine predator. Such data
      could be vital for understanding future population fluctuations that occur in
      response to the dynamic environment, as natural and anthropogenic factors
      continue to modify marine habitats. 

PMID- 24450365
TI  - Dose optimization for spinal treatment effectiveness: a randomized controlled
      trial investigating the effects of high and low mobilization forces in patients
      with neck pain.
AB  - STUDY DESIGN: Randomized controlled trial. Objective To determine if force
      magnitude during posterior-to-anterior mobilization affects immediate and short
      term outcomes in patients with chronic, nonspecific neck pain. BACKGROUND: The
      optimal dose of mobilization to effectively treat patients with neck pain is not
      known. METHODS: Patients with neck pain of at least 3 months in duration (n = 64)
      were randomized to receive a single treatment of posterior-to-anterior
      mobilization applied with 30 N or 90 N of mean peak force (3 sets of 30 seconds)
      or a placebo (detuned laser) on the spinous process at the painful spinal level.
      Pressure pain threshold, pain measured with a visual analog scale (range, 0-100
      mm), cervical range of motion, and spinal stiffness at the painful spinal level
      (measured with a custom device and normalized as a percentage of C7 stiffness)
      were assessed before, immediately after, and at a mean +/- SD follow-up of 4.0 +/
      1.8 days following treatment. Repeated-measures analysis of covariance and
      Bonferroni-adjusted post hoc tests determined group differences for each outcome
      measure after treatment and at follow-up. RESULTS: At follow-up, the 90-N group
      had less pain than the 30-N group (mean difference, 11.3 mm; 95% confidence
      interval: 0.1, 22.6 mm; P = .048) and lower stiffness than the placebo group
      (mean difference, 17.5%; 95% confidence interval: 4.2%, 30.9%; P = .006). These
      differences were not present immediately after treatment. There were no
      significant between-group differences in pressure pain threshold or range of
      motion after treatment or at follow-up. CONCLUSION: A specific dose of
      mobilization, in terms of applied force, appears necessary for reducing stiffness
      and potentially pain in patients with chronic neck pain. Changes were not
      observed immediately after mobilization, suggesting that its effects are not
      directly mechanical. TRIAL REGISTRATION: Australian and New Zealand Clinical
      Trials Registry ( http://www.anzctr.org.au/): ACTRN12611000374965. LEVEL OF
      EVIDENCE: Therapy, level 1b-.

PMID- 24450366
TI  - Assessment of strength, flexibility, and running mechanics in men with iliotibial
      band syndrome.
AB  - STUDY DESIGN: Cross-sectional laboratory study. OBJECTIVES: To assess differences
      in hip strength, iliotibial band length, and hip and knee mechanics during
      running between male runners with iliotibial band syndrome (ITBS) and healthy
      controls. BACKGROUND: Flexibility, strength, and running mechanics are commonly
      assessed in patients with ITBS. However, these variables have not been evaluated
      concurrently in this population. METHODS: Thirty-four men participated (17
      healthy, 17 ITBS). Hip strength was measured with a handheld dynamometer, and
      iliotibial band length was assessed using an inclinometer while performing the
      Ober test. Kinetic and 3-D kinematic data were obtained during running. Kinematic
      variables of interest included frontal and transverse plane hip and knee joint
      angles during early stance. Independent-samples t tests, as well as effect sizes,
      were used to assess group differences. RESULTS: Compared to the control group,
      persons with ITBS had a significantly lower Ober measurement (1.2 degrees ),
      weaker hip external rotators (1.2 Nm/kg), greater hip internal rotation (3.7
      degrees ), and greater knee adduction (3.6 degrees ). However, only hip internal
      rotation and knee adduction exceeded the minimal detectable difference value.
      CONCLUSION: Our results suggest that intervention strategies that target
      neuromuscular control of the hip and knee may be indicated for males with ITBS.

PMID- 24450367
TI  - Changes in biochemical markers of pain perception and stress response after
      spinal manipulation.
AB  - STUDY DESIGN: Controlled, repeated-measures, single-blind randomized study.
      OBJECTIVES: To determine the effect of cervical or thoracic manipulation on
      neurotensin, oxytocin, orexin A, and cortisol levels. BACKGROUND: Previous
      studies have researched the effect of spinal manipulation on pain modulation
      and/or range of movement. However, there is little knowledge of the biochemical
      process that supports the antinociceptive effect of spinal manipulation. METHODS:
      Thirty asymptomatic subjects were randomly divided into 3 groups: cervical
      manipulation (n = 10), thoracic manipulation (n = 10), and nonmanipulation
      (control) (n = 10). Blood samples were extracted before, immediately after, and 2
      hours after each intervention. Neurotensin, oxytocin, and orexin A were
      determined in plasma using enzyme-linked immuno assay. Cortisol was measured by
      microparticulate enzyme immuno assay in serum samples. RESULTS: Immediately after
      the intervention, significantly higher values of neurotensin (P<.05) and oxytocin
      (P<.001) levels were observed with both cervical and thoracic manipulation,
      whereas cortisol concentration was increased only in the cervical manipulation
      group (P<.05). No changes were detected for orexin A levels. Two hours after the
      intervention, no significant differences were observed in between-group analysis.
      CONCLUSION: The mechanical stimulus provided by spinal manipulation triggers an
      increase in neurotensin, oxytocin, and cortisol blood levels. Data suggest that
      the initial capability of the tissues to tolerate mechanical deformation affects
      the capacity of these tissues to produce an induction of neuropeptide expression.
      J

PMID- 24450368
TI  - Prognostic factors for successful recovery after arthroscopic rotator cuff
      repair: a systematic literature review.
AB  - STUDY DESIGN: Systematic literature review. OBJECTIVES: To perform a systematic
      review of the literature on prognostic factors for successful recovery after
      arthroscopic rotator cuff repair. BACKGROUND: Rotator cuff lesion is a common
      shoulder disorder, with a prevalence ranging from 13% in people over 50 years of
      age to more than 50% in people over 80 years of age. Several factors can affect
      the extent to which a person will recover after the surgical repair of a rotator
      cuff tear. More knowledge about these prognostic factors may lead to a better
      understanding of why the recovery process is successful in some patients but not
      in others. METHODS: A systematic literature search from 1995 to November 2013 was
      performed to identify studies reporting prognostic factors for successful
      recovery after arthroscopic rotator cuff repair. RESULTS: A total of 455 studies
      were initially identified, 10 of which were included in the review. For all
      included studies, the percentage of patients with complete tendon healing at
      final assessment ranged from 60% to 88%. Twelve prognostic factors, which could
      be divided into 4 categories, were identified as being associated with better
      recovery: demographic factors (younger age, male gender), clinical factors
      (higher bone mineral density, absence of diabetes mellitus, higher level of
      sports activity, greater preoperative range of motion, absence of obesity),
      factors related to cuff integrity (smaller sagittal size of the cuff lesion, less
      retraction of the cuff, less fatty infiltration, no multiple tendon involvement),
      and factors related to the surgical procedure (no concomitant biceps or
      acromioclavicular joint procedures). CONCLUSION: Knowledge and understanding of
      prognostic factors should be used in the decision-making process concerning
      arthroscopic rotator cuff repair to offer better care to patients. LEVEL OF
      EVIDENCE: Prognosis, level 2a-.

PMID- 24450369
TI  - Measuring health-related physical fitness in physiotherapy practice: reliability,
      validity, and feasibility of clinical field tests and a patient-reported measure.
AB  - STUDY DESIGN: A cross-sectional study with a test-retest design. OBJECTIVES: To
      assess measurement properties of the physical fitness questionnaire, the 6-minute
      walk test, the stair test, the hand-grip test, the 30-second sit-to-stand test,
      and the fingertip-to-floor test in patients with various musculoskeletal
      conditions (MSCs). BACKGROUND: Patients suffering from MSCs tend to be more
      deconditioned and less physically active than healthy people. Physiotherapists
      should, therefore, focus on health-related physical fitness in addition to their
      patients' specific MSCs to offer optimal treatment. To enable good decision
      making, a core set of feasible measures with acceptable measurement properties is
      needed. METHODS: Eighty-one patients with MSCs (57.6 +/- 14.2 years of age) were
      recruited from outpatient physiotherapy clinics. Relative reliability was
      analyzed with intraclass correlation coefficient model 2,1, and absolute
      reliability with standard error of measurement and smallest detectable change.
      Construct validity was assessed with a priori hypotheses. Time spent and
      assistance needed to accomplish the measures were used to assess feasibility.
      RESULTS: The 6-minute walk test, the hand-grip test, and the physical fitness
      questionnaire showed acceptable reliability (49 m, 4 kg, and 2 points,
      respectively) and construct validity. The stair test showed acceptable
      reliability (8 seconds) but not validity. The 30-second sit-to-stand test showed
      acceptable validity but not reliability (4 sit-to-stands), whereas the fingertip
      to-floor test showed neither acceptable reliability (9 cm) nor validity.
      CONCLUSION: The 6-minute walk test, the hand-grip test, and the physical fitness
      questionnaire can be recommended as a core set of reliable and valid measures to
      assess health-related physical fitness in patients with various MSCs.

PMID- 24450370
TI  - Efficacy of exercise intervention as determined by the McKenzie System of
      Mechanical Diagnosis and Therapy for knee osteoarthritis: a randomized controlled
      trial.
AB  - STUDY DESIGN: Randomized controlled trial. Objectives To examine the efficacy of
      exercise intervention in patients with knee osteoarthritis (OA), as directed by
      Mechanical Diagnosis and Therapy (MDT) assessment, and, secondarily, to explore
      outcomes between MDT assessment-defined subgroups within the exercise group.
      BACKGROUND: Due to the high physical and economic burden of knee OA, the
      effectiveness of conservative interventions and determining those patients who
      will respond to them should be investigated. METHODS: Patients with knee OA (n =
      180) were randomized to an exercise intervention group or a control group. The
      intervention group, in which patients classified as having knee derangements (MDT
      derangement) received MDT directional exercises and patients classified as
      nonresponders (MDT nonresponders) received evidence-based exercises, was compared
      to a control group that received no exercise intervention. Pain and function were
      assessed at baseline, 2 weeks, and 3 months, using the P4 pain scale and Knee
      injury and Osteoarthritis Outcome Score (KOOS) pain and function subscales. Two
      way analysis of covariance was used to examine treatment and time effects.
      Multiple comparisons were examined, and mean differences with 95% confidence
      intervals (CIs) were reported. RESULTS: The exercise intervention group had
      significantly improved P4 scores (mean difference, -6; 95% CI: -8, -3), KOOS pain
      scores (mean difference, 9; 95% CI: 5, 13), and KOOS function scores (mean
      difference, 11; 95% CI: 7, 15) compared to those of the control group at 2 weeks.
      At 3 months, the exercise intervention group had significantly improved KOOS pain
      scores (mean difference, 7; 95% CI: 3, 11) and KOOS function scores (mean
      difference, 5; 95% CI: 1, 9) compared to controls. CONCLUSION: Patients with knee
      OA who were prescribed exercises based on an MDT assessment had superior outcomes
      compared to those of wait-list controls. The MDT subgroup of knee derangement may
      warrant further investigation in patients with knee OA. Protocol registered at
      ClinicalTrials.gov (NCT01641874). LEVEL OF EVIDENCE: Therapy, level 1b-.

PMID- 24450371
TI  - Increased patellar tendon microcirculation and reduction of tendon stiffness
      following knee extension eccentric exercises.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To measure and compare
      patellar tendon stiffness and microcirculation in college tennis players and
      nonathletic students when performing eccentric knee extension exercises that do
      and do not reduce tendon stiffness. BACKGROUND: Previous studies suggest that
      tendon microcirculation response during exercises may vary based on the tendon's
      plastic properties. Methods The study included 3 groups of college-age male
      students: tennis players who performed 4 sets of either 40 (n = 12) or 80 (n =
      13) repetitions of eccentric knee extension exercise and nonathletic students (n
      = 14) who performed 4 sets of 40 repetitions. Tendon stiffness was measured
      before and after exercise completion. Changes in total hemoglobin and oxygen
      saturation (OSat) were analyzed while performing the 4 sets. Comparisons were
      made within and between the groups. The level of association between tendon
      microcirculation and stiffness reduction was assessed. RESULTS: The 2 groups
      (player/4 * 80 and student/4 * 40) exhibiting patellar tendon stiffness
      reductions (P<.008) showed higher total hemoglobin and OSat levels, above the pre
      exercise levels, in the fourth set compared to the first set of exercises
      (P<.004). The tennis players who performed 4 sets of 40 repetitions exhibited
      higher OSat levels in the fourth set than in the first set (P = .004) but had no
      reduction in tendon stiffness. Changes in OSat levels in the fourth set were
      correlated with patellar tendon stiffness reductions (r = -0.381, P = .02).
      CONCLUSION: We conclude that there was increased patellar tendon microcirculation
      after performing knee extension eccentric exercises that resulted in a reduction
      in tendon stiffness.

PMID- 24450372
TI  - Clinical observation of standing trunk movements: what do the aberrant movement
      patterns tell us?
AB  - STUDY DESIGN: Clinical measurement, cross-sectional study. OBJECTIVE: To
      investigate the reliability of observation of aberrant movement patterns (altered
      lumbopelvic rhythm, deviation from sagittal plane, instability catch or judder,
      and painful arc of motion) and to determine whether each pattern is associated
      with current low back pain (LBP). BACKGROUND: Identification of aberrant movement
      patterns during trunk motion is an important component of subclassifying patients
      with LBP and prescribing evidence-based interventions. However, reported
      reliability for observation of specific aberrant patterns is low, and observation
      of any aberrant pattern (clinical definition of positive test) has ranged from
      poor to moderate. In addition, the validity of the association of clinical
      observations of aberrant movements during forward bending with LBP or dysfunction
      has yet to be determined. METHODS: Experienced physical therapists simultaneously
      observed trunk movements of 102 subjects with no LBP, current LBP, or history of
      LBP. Kappa statistics were used to evaluate interrater agreement in identifying
      different types of aberrant patterns. Associations were used to determine the
      validity of the hypothesized relationship between aberrant patterns and LBP.
      RESULTS: Interrater reliability of identifying the different types of aberrant
      patterns in subjects with LBP ranged from fair (kappa = 0.35; 95% confidence
      interval: 0.00, 0.71) to excellent (kappa = 0.89; 95% confidence interval: 0.69,
      1.00). Using the clinical definition of 1 observation of any aberrant motion,
      interrater agreement was substantial (kappa = 0.65; 95% confidence interval:
      0.00, 1.00). Significant association was found between judder, deviation, and
      LBP. The frequency of observed aberrant patterns was significantly associated
      with LBP. CONCLUSION: Simultaneous observation for specific aberrant movement
      patterns suggests that identification can be performed with at least fair
      interrater agreement, and observation of any pattern with substantial agreement.
      Aberrant patterns are more frequently observed in patients with current
      complaints of LBP; however, they also appear in individuals with a history of LBP
      and no LBP.

PMID- 24450373
TI  - Spatial-temporal gait characteristics in individuals with hip osteoarthritis: a
      systematic literature review and meta-analysis.
AB  - STUDY DESIGN: Systematic literature review and meta-analysis. OBJECTIVE: To
      systematically review and critically evaluate the literature to determine how
      basic gait characteristics are altered in individuals with hip osteoarthritis
      (OA). BACKGROUND: Hip OA is a progressive musculoskeletal condition that leads to
      pain, stiffness, and functional limitation in activities such as walking.
      Understanding gait dysfunction in people with hip OA may contribute to more
      effective management of the disease. METHODS: Eleven electronic research
      databases were searched. Studies comparing basic gait parameters in individuals
      with hip OA to healthy controls and the affected to the contralateral limb of
      individuals with hip OA were included. The studies were critically appraised for
      methodological quality. Available data were extracted, and meta-analysis was
      performed, with standardized effect sizes (Cohen d) and corresponding 95%
      confidence intervals computed for gait speed, cadence, step and stride length,
      stance, swing and double-stance duration, and step width. RESULTS: The final
      analysis included 30 articles. Self-selected gait speed was 26% slower in
      individuals with hip OA relative to controls, which was explained by shorter
      stride length. Consistent evidence was found for greater asymmetry in individuals
      with hip OA than controls, with shorter step length and stance duration in the
      affected compared to the contralateral limb. CONCLUSION: Individuals with hip OA
      walk at a slower speed and exhibit greater gait asymmetry than controls. Gait
      speed and asymmetry can be readily assessed clinically and represent a simple way
      of objectively evaluating gait dysfunction and monitoring treatment progress in
      individuals with hip OA.

PMID- 24450374
TI  - Adult male circumcision in Nyanza, Kenya at scale: the cost and efficiency of
      alternative service delivery modes.
AB  - BACKGROUND: Adult male circumcision (MC) services in Kenya are provided through
      both horizontal and vertical programs, and via facility-based, mobile and
      outreach service delivery. This study assesses the costs and composition of unit
      costs for each program approach and service delivery mode and assess the cost
      effectiveness of each. METHODS: This study was conducted on the unit costs of
      adult MC delivery in 222 purposively-selected MC delivery sites in Nyanza
      Province, Kenya from November 2008 through April 2010 using program data from the
      AIDS, Population, and Health Integrated Assistance Project II (APHIA II) and from
      the Nyanza Reproductive Health Society (NRHS). The former program can be
      characterized as horizontal or integrated; the latter as 'diagonal'; containing
      both horizontal and vertical elements. Expenditure and services data were
      collected from project financial and monitoring documents and via discussions
      with program officials. In addition, per-case, direct service delivery costs were
      calculated using time and motion observations of 246 adult MC procedures
      performed during May and June, 2010. We calculated the cost per HIV infections
      averted for each of the service delivery modalities. RESULTS: Unit cost per adult
      MC was $38.62 and $44.24 for APHIA II and NRHS respectively, ranging from $29.32
      (APHIA II mobile) to $46.20 (NRHS outreach/mobile). Unit costs at base facilities
      was similar for the two approaches. Time and motion data revealed that the
      opportunity cost of the elapsed time between the arrival of the surgical team and
      the time the first MC procedure begins varies between $2.08 and $6.27 per case.
      The cost per HIV infection (HIA) averted ranged from $117.29 for mobile service
      via the horizontal APHIA-II program to $184.84 per HIA for the diagonal NRHS
      program. CONCLUSIONS: This study provides evidence for the similar efficiency of
      a horizontal approach (APHIA II) and a combination of horizontal and vertical
      approaches (NRHS) to support scale-up of adult MC services in Nyanza. Differences
      in unit cost are modest, not consistently in the same direction, and largely
      explained by differences in compensation levels.

PMID- 24450375
TI  - Pregnancy-induced metabolic phenotype variations in maternal plasma.
AB  - Metabolic variations occur during normal pregnancy to provide the growing fetus
      with a supply of nutrients required for its development and to ensure the health
      of the woman during gestation. Mass spectrometry-based metabolomics was employed
      to study the metabolic phenotype variations in the maternal plasma that are
      induced by pregnancy in each of its three trimesters. Nontargeted metabolomics
      analysis showed that pregnancy significantly altered the profile of metabolites
      in maternal plasma. The levels of six metabolites were found to change
      significantly throughout pregnancy, with related metabolic pathway variations
      observed in biopterin metabolism, phospholipid metabolism, amino acid
      derivatives, and fatty acid oxidation. In particular, there was a pronounced
      elevation of dihydrobiopterin (BH2), a compound produced in the synthesis of
      dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas
      it was markedly decreased in the third trimester. The turnover of BH2 and
      tryptophan catabolites indicated that the fluctuations of neurotransmitters
      throughout pregnancy might reveal the metabolic adaption in the maternal body for
      the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species
      were also determined and this showed variations in the presence of long-chain
      acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of
      acylcarnitines and lysophospholipids to meet the energy demands in pregnant
      women. To our knowledge, this work is the first report of dynamic metabolic
      signatures and proposed related metabolic pathways in the maternal plasma for
      normal pregnancies and provided the basis for time-dependent metabolic trajectory
      against which disease-related disorders may be contrasted.

PMID- 24450376
TI  - Incidence and predictors of venous thromboembolism recurrence after a first
      isolated distal deep vein thrombosis.
AB  - BACKGROUND: Isolated distal deep vein thrombosis (iDDVT) (i.e. without proximal
      DVT or pulmonary embolism) represents half of all cases of lower limb DVT. Its
      clinical significance and management are controversial. Data on long-term follow
      up are scarce, especially concerning risk and predictors of venous
      thromboembolism (VTE) recurrence. METHODS: Using data from the OPTIMEV
      (OPTimisation de l'Interrogatoire dans l'evaluation du risque throMbo-Embolique
      Veineux) study, a prospective, observational, multicenter study, we compared, 3
      years after an index VTE event and after discontinuation of anticoagulants, (i)
      the incidence and type of recurrence in patients without cancer with a first
      iDDVT vs. a first isolated proximal DVT (iPDVT) and (ii) predictors of recurrence
      after iDDVT. RESULTS: Compared with patients with iPDVT (n = 259), patients with
      an iDDVT (n = 490) had a lower annualized incidence of overall VTE recurrence
      (5.2% [95% confidence interval 3.6-7.6] vs. 2.7% [1.9-3.8], respectively; P =
      0.02) but a similar incidence of pulmonary embolism recurrence (1.0% [0.5-2.3]
      vs. 0.9% [0.5-1.6], respectively; P = 0.83). An age of > 50 years, unprovoked
      character of index iDDVT, and involvement of more than one vein in one or both
      legs each independently tripled the risk of recurrence, with the latter then
      being >= 3% per patient-year. Neither muscular vein nor deep-calf vein location
      of iDDVT nor clot diameter with compression influenced the risk of recurrence.
      CONCLUSIONS: After stopping anticoagulants, patients with iDDVT have a
      significantly lower risk of overall VTE recurrence than did patients with iPDVT
      but a similar risk of serious recurrent VTE. Age > 50 years, unprovoked iDDVT,
      and number of thrombosed veins (more than one) influenced the risk of recurrence
      and may help to define patients at significant risk of recurrence.

PMID- 24450381
TI  - Dendritic cells, T-cells and epithelial cells: a crucial interplay in
      immunopathology of primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease that is
      characterized by mononuclear cell infiltration of exocrine glands. T-cells have
      been shown to play a central role in tissue destruction and regulation of B-cell
      activity and the production of autoantibodies typifying pSS. Despite the fact
      that dendritic cells (DCs) are candidate key players in the activation of T- and
      B-cells in pSS, their contribution has been under evaluated. This manuscript
      reviews current insights in DC biology and examines literature on the role of DCs
      in the immunopathology of primary Sjogren's syndrome, focusing on the interplay
      between dendritic cells, epithelial cells and T-cells. 

PMID- 24450377
TI  - Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for
      tuberculous meningitis.
AB  - RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives,
      but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We
      investigated whether the detection of intracellular bacteria by a modified Ziehl
      Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid
      leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal
      fluid specimens from patients with suspected tuberculous meningitis were stained
      by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving
      cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain.
      Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy.
      All tests were performed prospectively in a central laboratory by experienced
      technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN
      RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis
      were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from
      cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis;
      the rest had probable or possible tuberculous meningitis according to published
      criteria. Against a clinical diagnostic gold standard the sensitivity of
      conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%),
      compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl
      Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6
      immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by
      the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and
      ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95%
      confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial
      detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6
      intracellular stain improve the laboratory diagnosis of tuberculous meningitis.

PMID- 24450382
TI  - Beverage intake in early childhood and change in body fat from preschool to
      adolescence.
AB  - BACKGROUND: Childhood obesity is closely associated with adult obesity,
      hypertension, and cardiovascular disease. This study's aim was to determine the
      effects of beverage intake patterns on body composition from early childhood into
      adolescence in the Framingham Children's Study. METHODS: Multiple sets of 3-day
      records were used to assess diet over 12 years, beginning in 1987, in 103 non
      Hispanic white boys and girls. BMI, waist circumference, and four skinfolds
      (triceps, subscapular, suprailiac, and abdominal) were measured yearly. Percent
      body fat was assessed by dual-energy X-ray absorptiometry at end of follow-up.
      Analysis of covariance and longitudinal mixed modeling were used to control for
      potential confounding by age, baseline body fat, percent of energy from fat,
      television/video viewing time, other beverage intakes not included in exposure
      group, mother's education, and BMI. RESULTS: Children with the lowest milk
      intakes in early childhood had 7.4% more body fat in later adolescence than those
      with higher intakes (30.0% body fat in tertile 1 vs. 22.6% in tertile 3;
      p=0.0095). Fruit and vegetable juice was similarly protective-those in the
      highest tertile of fruit and vegetable juice intake during childhood had an 8.0
      cm smaller waist circumference at 15-17 years of age, compared with those in the
      lowest tertile (p=0.0328). There was no relation between sugar-sweetened
      beverages (SSBs) and percent body fat (p=0.9296) or other outcomes. CONCLUSIONS:
      These results suggest that adequate intakes of milk and fruit and vegetable juice
      may reduce the risk of excess body fat in later childhood and adolescence.
      Further, modest intakes of SSBs in early childhood may not adversely affect body
      fat change.

PMID- 24450383
TI  - Are our children "diseased"?

PMID- 24450384
TI  - Caregiver and adolescent responses to food and beverage marketing exposures
      through an online survey.
AB  - BACKGROUND: The Institute of Medicine noted that current food and beverage
      marketing practices promote unhealthful diets. However, little public health
      research has been conducted on food marketing directed toward adolescents,
      especially using caregiver- and adolescent-reported data. METHODS: We assessed
      perceived frequency of food/beverage advertising exposure and common locations of
      food/beverage marketing exposure for adolescents using 2012 Summer ConsumerStyles
      and YouthStyles survey data on US adults >=18 years of age and their children
      ages 12-17 (n=847), respectively. Exposure to advertisements for fast food, soda,
      fruit drinks, sports drinks, energy drinks, and bottled water were categorized as
      <1 time/week, 1-6 times/week, and >=1 time/day, and don't know. Weighted chi
      square tests were used to examine the difference between caregivers' and
      adolescents' responses. RESULTS: The majority of caregivers and adolescents
      reported that adolescents viewed advertisements >=1 time/day across all
      food/beverage categories with the highest, at least daily, exposure reported for
      fast food. Caregivers more frequently reported that adolescents viewed all
      food/beverage advertisements >=1 time/day than the adolescents reported (chi
      square tests, p<0.0001). Both caregivers and adolescents reported that the
      adolescents view food/beverage marketing most frequently on television followed
      by at the supermarket. CONCLUSIONS: Our study showed that adolescents reported
      lower frequency of food and beverage advertising exposure than their caregivers.
      Further research may be needed to verify self-reported exposure data on food and
      beverage advertising as a way to obtain data for use in research on its
      relationship with diet quality and obesity.

PMID- 24450385
TI  - Designing and evaluating an interprofessional shared decision-making and goal
      setting decision aid for patients with diabetes in clinical care--systematic
      decision aid development and study protocol.
AB  - BACKGROUND: Care of patients with diabetes often occurs in the context of other
      chronic illness. Competing disease priorities and competing patient-physician
      priorities present challenges in the provision of care for the complex patient.
      Guideline implementation interventions to date do not acknowledge these
      intricacies of clinical practice. As a result, patients and providers are left
      overwhelmed and paralyzed by the sheer volume of recommendations and tasks. An
      individualized approach to the patient with diabetes and multiple comorbid
      conditions using shared decision-making (SDM) and goal setting has been advocated
      as a patient-centred approach that may facilitate prioritization of treatment
      options. Furthermore, incorporating interprofessional integration into practice
      may overcome barriers to implementation. However, these strategies have not been
      taken up extensively in clinical practice. OBJECTIVES: To systematically develop
      and test an interprofessional SDM and goal-setting toolkit for patients with
      diabetes and other chronic diseases, following the Knowledge to Action framework.
      METHODS: 1. Feasibility study: Individual interviews with primary care
      physicians, nurses, dietitians, pharmacists, and patients with diabetes will be
      conducted, exploring their experiences with shared decision-making and priority
      setting, including facilitators and barriers, the relevance of a decision aid and
      toolkit for priority-setting, and how best to integrate it into practice.2.
      Toolkit development: Based on this data, an evidence-based multi-component SDM
      toolkit will be developed. The toolkit will be reviewed by content experts
      (primary care, endocrinology, geriatricians, nurses, dietitians, pharmacists,
      patients) for accuracy and comprehensiveness.3. Heuristic evaluation: A human
      factors engineer will review the toolkit and identify, list and categorize
      usability issues by severity.4. Usability testing: This will be done using
      cognitive task analysis.5. Iterative refinement: Throughout the development
      process, the toolkit will be refined through several iterative cycles of feedback
      and redesign. DISCUSSION: Interprofessional shared decision-making regarding
      priority-setting with the use of a decision aid toolkit may help prioritize care
      of individuals with multiple comorbid conditions. Adhering to principles of user
      centered design, we will develop and refine a toolkit to assess the feasibility
      of this approach.

PMID- 24450387
TI  - Synthesis and characterization of binary-complex models of ureas and 1,3
      dicarbonyl compounds: deeper insights into reaction mechanisms using snap-shot
      structural analysis.
AB  - The mechanism of the enantioselective Mannich reaction catalyzed by a hydrogen
      bond (HB)-donor bifunctional organocatalyst has been fully investigated using
      experimental evidence and computational analysis. Several binary complexes have
      been designed as models of a catalyst and a nucleophile, where the urea moieties
      were linked to a 1,3-dicarbonyl compound through the diphenylacetylene motif. X
      ray analysis of models 9 and 10 showed that the two N-H protons of the ureas
      interacted with the same carbonyl group via a double HB interaction. Further
      investigation of the crystallographic structure of 11 allowed for the direct
      observation of the labile ammonium-enolate intermediate formed between a
      bifunctional amino urea and 1,3-diketone. The beta-keto ester-amino urea complex
      12 reacted with several electrophiles at a remarkably fast rate to provide the
      corresponding adducts 15 and 17 as single diastereomers in excellent yields,
      respectively. A density functional theory calculation disclosed the details of
      the deprotonation and C-C bond-forming steps of the enantioselective Mannich
      reaction. The deprotonation of the 1,3-dicarbonyl moiety occurred predominantly
      via the enol form to give the ammonium--enolate intermediate. These results
      should provide a deeper and more accurate understanding of the functional roles
      of the HB-donor and Bronsted base moieties of the catalyst. 

PMID- 24450386
TI  - European Treatment and Outcome Study score does not predict imatinib treatment
      response and outcome in chronic myeloid leukemia patients.
AB  - The Sokal and Hasford scores were developed in the chemotherapy and interferon
      era and are widely used as prognostic indicators in patients with chronic myeloid
      leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS)
      scoring system was developed. We performed a multicenter retrospective study to
      validate the effectiveness of each of the three scoring systems. The study cohort
      included 145 patients diagnosed with CML in chronic phase who were treated with
      imatinib. In the EUTOS low- and high-risk groups, the cumulative incidence of
      complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797)
      and the 5-year overall survival rate was 92.6% and 93.3% (P = 0.871),
      respectively. The cumulative incidence of CCyR at 12 months, 5-year event-free
      survival and 5-year progression-free survival were not predicted using the EUTOS
      scoring system. However, there were significant differences in both the Sokal
      score and Hasford score risk groups. In our retrospective validation study, the
      EUTOS score did not predict the prognosis of patients with CML in chronic phase
      treated with imatinib.

PMID- 24450388
TI  - Inhibitors of catechol-O-methyltransferase in the treatment of neurological
      disorders.
AB  - Catechol-O-methyltransferase (COMT) is the enzyme which catalyzes the transfer of
      a methyl group from S-adenosylmethionine to catechols and catecholamines, like
      the neurotransmitters dopamine, epinephrine and norepinephrine. COMT has
      implications in many neurological and psychiatric disorders like schizophrenia,
      Parkinson's disease (PD), bipolar disorders, etc. and therefore, it serves as an
      important drug target. Since its characterization in 1957, many inhibitors were
      designed where the first generation inhibitors were found to be highly toxic,
      short acting and had poor bioavailability. Currently, two of the second
      generation inhibitors, tolcapone and entacapone have been used for treatment of
      PD but are associated with various dopaminergic and gastro-intestinal side
      effects. There have been several approaches for the design of novel COMT
      inhibitors with a good and safe therapeutic profile. The focus of this article is
      to review the current knowledge on COMT and the role of COMT inhibitors in the
      treatment of neurological disorders. The inhibitors have been classified into six
      different classes based on the structural framework. A historical overview of the
      discovery and development of COMT inhibitors is presented with a special emphasis
      on new generation of inhibitors till date. 

PMID- 24450389
TI  - From screening to postpartum follow-up - the determinants and barriers for
      gestational diabetes mellitus (GDM) services, a systematic review.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) - a transitory form of diabetes
      first recognised during pregnancy complicates between < 1% and 28% of all
      pregnancies. GDM has important short and long-term health consequences for both
      the mother and her offspring. To prevent adverse pregnancy outcomes and to
      prevent or delay future onset of type 2 diabetes in mother and offspring, timely
      detection, optimum treatment, and preventive postpartum care and follow-up is
      necessary. However the area remains grossly under-prioritised. METHODS: To
      investigate determinants and barriers to GDM care from initial screening and
      diagnosis to prenatal treatment and postpartum follow-up, a PubMed database
      search to identify quantitative and qualitative studies on the subject was done
      in September 2012. Fifty-eight relevant studies were reviewed. RESULTS: Adherence
      to prevailing GDM screening guidelines and compliance to screening tests seems
      sub-optimal at best and arbitrary at worst, with no clear or consistent
      correlation to health care provider, health system or client characteristics.
      Studies indicate that most women express commitment and motivation for behaviour
      change to protect the health of their unborn baby, but compliance to recommended
      treatment and advice is fraught with challenges, and precious little is known
      about health system or societal factors that hinder compliance and what can be
      done to improve it. A number of barriers related to health care provider/system
      and client characteristics have been identified by qualitative studies.
      Immediately following a GDM pregnancy many women, when properly informed, desire
      and intend to maintain healthy lifestyles to prevent future diabetes, but find
      the effort challenging. Adherence to recommended postpartum screening and
      continued lifestyle modifications seems even lower. Here too, health care
      provider, health system and client related determinants and barriers were
      identified. Studies reveal that sense of self-efficacy and social support are key
      determinants. CONCLUSIONS: The paper identifies and discusses determinants and
      barriers for GDM care, fully recognising that these are highly dependent on the
      context.

PMID- 24450391
TI  - Amitriptyline, clomipramine, and doxepin adsorption onto sodium polystyrene
      sulfonate.
AB  - PURPOSE OF THE STUDY: Comparative in vitro studies were carried out to determine
      the adsorption characteristics of 3 drugs on activated charcoal (AC) and sodium
      polystyrene sulfonate (SPS). Activated charcoal (AC) has been long used as
      gastric decontamination agent for tricyclic antidepressants (TCA). METHODS:
      Solutions containing drugs (amitriptyline, clomipramine, or doxepin) and variable
      amount of AC or SPS were incubated for 30 minutes. RESULTS: At pH 1.2 the
      adsorbent: drug mass ratio varied from 2 : 1 to 40 : 1 for AC, and from 0.4 : 1
      to 8 : 1 for SPS. UV-VIS spectrophotometer was used for the determination of free
      drug concentrations. The qmax of amitriptyline was 0.055 mg/mg AC and 0.574 mg/mg
      SPS, qmax of clomipramine was 0.053 mg/mg AC and 0.572 mg/mg SPS, and qmax of
      doxepin was 0.045 mg/mg AC and 0.556 mg/mg SPS. The results of adsorption
      experiments with SPS revealed higher values for the qmax parameters in comparison
      with AC. CONCLUSION: In vitro gastric decontamination experiments for
      antidepressant amitriptyline, clomipramine, and doxepin showed that SPS has
      higher qmax values than the corresponding experiments with AC. Therefore, we
      suggest SPS is a better gastric decontaminating agent for the management of acute
      TCA intoxication.

PMID- 24450392
TI  - Proteome profiling of mitotic clonal expansion during 3T3-L1 adipocyte
      differentiation using iTRAQ-2DLC-MS/MS.
AB  - Mitotic clonal expansion (MCE) is one of the important events taking place at the
      early stage during 3T3-L1 adipocyte differentiation. To investigate the mechanism
      underlying this process, we carried out a temporal proteomic analysis to profile
      the dynamic changes in MCE. Using 8-plex-iTRAQ-2DLC-MS/MS analysis, 3152 proteins
      were quantified during the initial 28 h of 3T3-L1 adipogenesis. Functional
      analysis was performed on 595 proteins with maximum or minimum quantities at 20 h
      of adipogenic induction that were potentially involved in MCE, which identified
      PI3K/AKT/mTOR as the most relevant pathway. Among the 595 proteins, PKM2
      (Pyruvate kinase M2), a patterned protein identified as a potential target gene
      of C/EBPbeta in our previous work, was selected for further investigation.
      Network analysis suggested positive correlations among C/EBPbeta, PIN1, and PKM2,
      which may be related with the PI3K-AKT pathway. Knockdown of PKM2 with siRNA
      inhibited both MCE and adipocyte differentiation of 3T3-L1 cells. Moreover, PKM2
      was down-regulated at both the mRNA level and the protein level upon the
      knockdown of C/EBPbeta. And overexpressed PKM2 can partially restore MCE,
      although it did not restore terminal adipocyte differentiation, which was
      inhibited by siC/EBPbeta. Thus, PKM2, potentially regulated by C/EBPbeta, is
      involved in MCE during adipocyte differentiation. The dynamic proteome changes
      quantified here provide a promising basis for revealing molecular mechanism
      regulating adipogenesis. 

PMID- 24450394
TI  - Marital satisfaction of Chinese mothers of children with autism and intellectual
      disabilities in Hong Kong.
AB  - BACKGROUND: Previous research showed an association among perceived stigma,
      perceived caregiving burden and marital satisfaction of mothers. However, little
      is known about their relationship among mothers of young children with
      disabilities in the Chinese context. The mediating role of perceived caregiving
      burden between perceived stigma and marital satisfaction was seldom explored.
      Hence, the present study aims to investigate the relationship between perceived
      stigma, perceived caregiving burden and marital satisfaction of Chinese mothers
      of children with intellectual disabilities or autism spectrum disorders in Hong
      Kong. METHODS: A cross-sectional survey using convenience sampling was conducted
      with mothers of pre-school children with disabilities aged from 2 to 6. A total
      of 160 completed questionnaires were collected from five special child care
      centres in Hong Kong. RESULTS: The findings in the hierarchical regression
      analyses showed that perceived stigma and perceived caregiving burden were
      significant predictors of mothers' marital satisfaction. Perceived burden,
      including perceived social burden, emotional burden and developmental burden but
      excluding time-dependence and physical burden, were found to be significant
      mediators between perceived stigma and marital satisfaction. CONCLUSION: To
      address the negative consequences brought on by stigma, measures can be taken to
      prevent stigmatisation and minimise the harmful effects. To alleviate mothers'
      perceived burden, Acceptance and Commitment Therapy, mutual support groups and
      psycho-educational and skills training programmes can be conducted for the
      mothers.

PMID- 24450395
TI  - Mechanistic studies of the rhodium-catalyzed direct C-H amination reaction using
      azides as the nitrogen source.
AB  - Direct C-H amination of arenes offers a straightforward route to aniline
      compounds without necessitating aryl (pseudo)halides as the starting materials.
      The recent development in this area, in particular in the metal-mediated
      transformations, is significant with regard to substrate scope and reaction
      conditions. Described herein are the mechanistic details on the Rh-catalyzed
      direct C-H amination reaction using organic azides as the amino source. The most
      important two stages were investigated especially in detail: (i) the formation of
      metal nitrenoid species and its subsequent insertion into a rhodacycle
      intermediate, and (ii) the regeneration of catalyst with concomitant release of
      products. It was revealed that a stepwise pathway involving a key Rh(V)-nitrenoid
      species that subsequently undergoes amido insertion is favored over a concerted C
      N bond formation pathway. DFT calculations and kinetic studies suggest that the
      rate-limiting step in the current C-H amination reaction is more closely related
      to the formation of Rh-nitrenoid intermediate rather than the presupposed C-H
      activation process. The present study provides mechanistic details of the direct
      C-H amination reaction, which bears both aspects of the inner- and outer-sphere
      paths within a catalytic cycle. 

PMID- 24450393
TI  - Impact of contrast agent viscosity on coronary balloon deflation times: bench
      testing results.
AB  - OBJECTIVES: To assess the impact of viscosity on angioplasty balloon deflation
      times. BACKGROUND: Lower contrast viscosity could result in more rapid coronary
      balloon deflation times. METHODS: We performed a bench comparison of coronary
      balloon deflation times using 2 contrast agents with different viscosity
      (ioxaglate and iodixanol), 3 contrast dilutions, and 2 inflation syringe filling
      volumes. Ten identical pairs of coronary angioplasty balloons were used to
      conduct each comparison after balloon inflation to 12 atmospheres. Simultaneous
      deflations were performed under cineangiography. The time to full contrast
      extraction and the area of contrast remaining after 5 seconds of deflation
      (quantified by opaque pixel count) were compared between groups. RESULTS: The
      mean time to full contrast extraction during balloon deflation was 8.3 +/- 2.5
      seconds for ioxaglate (lower viscosity) versus 10.1 +/- 2.9 seconds for iodixanol
      (higher viscosity) (17.4% decrease, P = 0.005), with a 35.6% (P = 0.004)
      reduction in contrast area at 5 seconds. Compared to 1:1 ioxaglate-saline
      mixture, 1:2 and 1:3 ioxaglate/saline mixes resulted in 26.7% (P < 0.001) and
      39.0% (P < 0.001) reduction in mean balloon deflation time, respectively, but at
      the expense of decreased balloon opacity. Filling the inflation syringe with 5
      versus 15 ml of contrast/saline solution was associated with 7.5% decrease in
      balloon deflation time (P = 0.005), but no difference in contrast area at 5
      seconds (P = 0.749). CONCLUSIONS: Use of a lower viscosity contrast agent and
      higher contrast dilution significantly reduced coronary balloon deflation times,
      whereas use of lower syringe filling volume had a modest effect. Rapid coronary
      balloon deflation could improve the safety of interventional procedures.

PMID- 24450390
TI  - Alterations in left ventricular, left atrial, and right ventricular structure and
      function to cardiovascular risk factors in adolescents with type 2 diabetes
      participating in the TODAY clinical trial.
AB  - Data on cardiovascular disease (CVD) risk in adolescents with type 2 diabetes
      (T2D) are limited. Echocardiography was performed in the last year of the
      Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical
      trial (median 41/2 yr from diagnosis of T2D, average age 18 yr), including MMode
      and 2D measurements of left ventricular (LV) and left atrial (LA) dimensions, LV
      tissue Doppler imaging (TDI), and tricuspid annular plane systolic excursion
      (TAPSE). Relationships between cardiac structure and function with demographic
      characteristics and baseline and change-from-baseline in CVD risk factors were
      examined in 455 participants. Mean LV mass (LVM) was high/normal and 16.2% had
      adverse LV geometry (8.1% concentric geometry, 4.5% LV hypertrophy, and 3.6%
      both). Determinants of higher LVM were male gender, black race, baseline and
      increasing body mass index (BMI), baseline and increasing systolic blood pressure
      (SBP), use of blood pressure (BP) medications, maintenance of glycemic control,
      and smoking; heart rate (HR) was inversely related. LV shortening fraction was
      high/normal and related to increasing BMI and higher baseline SBP. LV relative
      wall thickness was related to race-ethnicity, change in BMI, baseline glycated
      hemoglobin (HbA1c), and baseline and change in SBP. Mean LA internal dimension
      was high/normal and gender, baseline and increasing BMI, increasing SBP, and HR
      (inverse) were related. LV TDI was positively related to obesity (higher with
      adverse geometry). TAPSE was normal and related to higher baseline BMI and lower
      HR. There was no effect of T2D treatment on cardiac target organ injury.
      Adolescents with T2D have adverse measures of cardiac structure and function
      positively related to BMI and BP. 

PMID- 24450398
TI  - The clinical utility of bronchoalveolar lavage in interstitial lung disease - is
      it really useful?
AB  - Bronchoalveolar lavage (BAL) can be a very useful tool in the diagnosis of
      interstitial lung disease, but BAL must be performed properly and the retrieved
      BAL fluid adequately processed and analyzed to allow accurate conclusions to be
      drawn from BAL analysis. A differential cell count of nucleated immune cells can
      show cell patterns that suggest or support certain diagnoses, and other testing
      (stains and cultures for infectious pathogens, malignant cell cytology) can be
      performed on BAL fluid that can also aid in diagnosis. When combined with the
      results of a careful history, physical examination, thoracic imaging, and other
      pertinent laboratory testing, the BAL analysis may allow a confident diagnosis of
      a specific interstitial lung disease to be made without proceeding to more
      invasive testing (e.g., surgical lung biopsy) that is associated with increased
      risk of complications. 

PMID- 24450399
TI  - Atopy and the gastrointestinal tract--a review of a common association in
      unexplained gastrointestinal disease.
AB  - In addition to diseases conventionally associated with atopy there is increasing
      recognition that atopy is also linked to a spectrum of gastrointestinal (GI)
      manifestations, including food allergy, primary eosinophilic GI disease,
      functional gastrointestinal disorders, gluten interactions, gastroesophageal
      reflux disease and inflammatory bowel disease. These associations may be
      underpinned by shared genetic susceptibilities, initiation of related immune
      pathways and common patterns of exposure to environmental cues, including
      allergen/pathogen encounters and variations in the composition of the intestinal
      microbiota. Further scrutiny of GI diseases with prominent allergic-type immune
      responses may yet redefine treatment paradigms for these common and important
      atopy-associated diseases. Looking forward, interventions by manipulation of the
      microbiota or host immune responses hold promise, but there is still room for
      further exploration of this novel field of host susceptibility, host-microbe
      interactions and atopy-associated GI diseases. 

PMID- 24450397
TI  - Atmospheric methane oxidizers are present and active in Canadian high Arctic
      soils.
AB  - The melting of permafrost and the associated potential for methane emissions to
      the atmosphere are major concerns in the context of global warming. However,
      soils can also represent a significant sink for methane through the activity of
      methane-oxidizing bacteria (MOB). In this study, we looked at the activity,
      diversity, and community structure of MOB at two sampling depths within the
      active layer in three soils from the Canadian high Arctic. These soils had the
      capacity to oxidize methane at low (15 ppm) and high (1000 ppm) methane
      concentrations, but rates differed greatly depending on the sampling date, depth,
      and site. The pmoA gene sequences related to two genotypes of uncultured MOB
      involved in atmospheric methane oxidation, the 'upland soil cluster gamma' and
      the 'upland soil cluster alpha', were detected in soils with near neutral and
      acidic pH, respectively. Other groups of MOB, including Type I methanotrophs and
      the 'Cluster 1' genotype, were also detected, indicating a broader diversity of
      MOB than previously reported for Arctic soils. Overall, the results reported here
      showed that methane oxidation at both low and high methane concentrations occurs
      in high Arctic soils and revealed that different groups of atmospheric MOB
      inhabit these soils.

PMID- 24450400
TI  - Sphingosine 1-phosphate increases an intracellular Ca(2+) concentration via S1P3
      receptor in cultured vascular smooth muscle cells.
AB  - OBJECTIVE: We investigated the effect of sphingosine 1-phosphate (S1P) on
      intracellular Ca(2+) dynamics in rat vascular smooth muscle cells (VSMCs).
      METHODS: Intracellular Ca(2+) concentration ([Ca(2+) ]i) was determined using a
      fluorescence dye fura-2/AM. Small interfering RNAs (siRNA) were transfected into
      VSMCs to deplete the expression of S1P2 and S1P3 receptors. KEY FINDINGS: S1P
      induced a rapid and transient elevation in [Ca(2+) ]i, which was maximal 1 min
      after the stimulation, followed by a sustained increase. When extracellular
      Ca(2+) was removed, a decrease in resting level and a small and transient
      increase in [Ca(2+) ]i by S1P stimulation were observed. siRNA targeted for the
      S1P3 receptor almost completely inhibited the S1P-induced increase in [Ca(2+) ]i.
      The rapid and transient increase in [Ca(2+) ]i was significantly inhibited by
      diltiazem at a high concentration. Pertussis toxin and a phospholipase C (PLC)
      inhibitor inhibited the S1P-induced increase in [Ca(2+) ]i regardless of the
      presence of extracellular Ca(2+) . Furthermore, S1P activated store-operated and
      receptor-operated Ca(2+) entry. CONCLUSIONS: These results suggest that S1P
      increases [Ca(2+) ]i via the S1P3 receptor by inducing an influx of extracellular
      Ca(2+) partially through the voltage-dependent Ca(2+) channels, as well as by
      mobilizing Ca(2+) from its intracellular stores. S1P3 receptor-coupled Gi/o
      protein and PLC activation mediate the mechanisms.

PMID- 24450401
TI  - Activatable organic near-infrared fluorescent probes based on a bacteriochlorin
      platform: synthesis and multicolor in vivo imaging with a single excitation.
AB  - Near infrared (NIR) fluorescent probes are ideal for in vivo imaging because they
      offer deeper tissue penetration and lower background autofluorescence. Although
      most fluorophores in this range are cyanine-based dyes, several new classes of
      fluorescent NIR probes have been developed. In this study, we developed organic
      bacteriochlorin derivatives, NMP4 and NMP5, which are excited with a single green
      light and emit different narrow, well-resolved bands in the NIR (peak of 739 and
      770 nm for NMP4 and NMP5, respectively). When conjugated to galactosyl-human
      serum albumin (hGSA) or glucosyl-human serum albumin (glu-HSA), both targeting H
      type lectins, including the beta-d-galactose receptor expressing on ovarian
      cancer, these agents become targeted, activatable, single excitation, multicolor
      NIR fluorescence probes. After conjugation to either glu-HSA or hGSA, substantial
      quenching of fluorescence occurs that is reversed after cell binding and
      internalization. In vitro studies showed higher cancer cell uptake with NMP4 or
      NMP5 conjugated to hGSA compared to the same conjugates with glu-HSA. In vivo
      single excitation two-color imaging was performed after intraperitoneal injection
      of these agents into mice with disseminated ovarian cancer. Excited with a single
      green light, distinct NIR emission spectra from each fluorophore were detected
      and could be distinguished with spectral unmixing. In vivo results using a red
      fluorescence protein (RFP) labeled tumor model of disseminated ovarian cancer
      demonstrated high sensitivity and specificity for all probes. The success of
      single excitation, 2-color NIR fluorescence imaging with a new class of
      bacteriochlorin-based activatable fluorophores, NMP4 and NMP5, paves the way for
      further exploration of noncyanine dye-based NIR fluorophores. 

PMID- 24450402
TI  - Platelets store laminins 411/421 and 511/521 in compartments distinct from alpha-
      or dense granules and secrete these proteins via microvesicles.
AB  - BACKGROUND: Blood platelets secrete upon activation of laminins 411/421 and
      511/521, large adhesive proteins mainly found in the basement membranes of blood
      vessels and other tissues. At present, the subcellular localization and secretion
      mechanisms of platelet laminins are largely unknown. OBJECTIVES: Our aim was to
      compare the subcellular localization of laminins 411/421 and 511/521 and specific
      granule markers in platelets. We also elucidated the role of microvesicles and
      exosomes in laminin release in platelet activation. METHODS: We studied laminin
      and granule marker protein localization in platelets by using immunofluorescence
      confocal microscopy and immunoelectron microscopy. Microvesicles and exosomes
      were separated from material released from platelets on activation by thrombin.
      The expression of laminins in microvesicles and exosomes was studied by using SDS
      PAGE and Western blotting as well as by flow cytometric analysis. The exosomes
      were immunoprecipitated with magnetic microbeads coated with anti-CD63
      antibodies. RESULTS AND CONCLUSIONS: We demonstrate that laminins 411/421 and
      511/521 are present in compartments of platelets that do not express alpha
      granule, dense granule, or lysosome marker proteins. Moreover, laminins secreted
      by activated platelets are mostly found in microvesicles shed from the plasma
      membrane, while their presence in simultaneously released exosomes is minimum.

PMID- 24450403
TI  - Exercise-induced capillary growth in human skeletal muscle and the dynamics of
      VEGF.
AB  - In skeletal muscle, growth of capillaries is an important adaptation to exercise
      training that secures adequate diffusion capacity for oxygen and nutrients even
      at high-intensity exercise when increases in muscle blood flow are profound.
      Mechanical forces present during muscle activity, such as shear stress and
      passive stretch, lead to cellular signaling, enhanced expression of angiogenic
      factors, and initiation of capillary growth. The most central angiogenic factor
      in skeletal muscle capillary growth is VEGF. During muscle contraction, VEGF
      increases in the muscle interstitium, acts on VEGF receptors on the capillary
      endothelium, and thereby stimulates angiogenic processes. A primary source of
      muscle interstitial VEGF during exercise is the skeletal muscle fibers which
      contain large stores of VEGF within vesicles. We propose that, during muscle
      activity, these VEGF-containing vesicles are redistributed toward the sarcolemma
      where the contents are secreted into the extracellular fluid. VEGF mRNA
      expression is increased primarily after exercise, which allows for a more rapid
      replenishment of VEGF stores lost through secretion during exercise. Future
      studies should focus on elucidating mechanisms and regulation of VEGF secretion.

PMID- 24450404
TI  - The effect of radiation therapy on the mechanical and morphological properties of
      the enamel and dentin of deciduous teeth--an in vitro study.
AB  - PURPOSE: To evaluate the effects of radiation therapy on deciduous teeth.
      MATERIALS AND METHODS: The enamel and dentin microhardness (n = 12) was evaluated
      at 3 depths, both before (control) and after each 10 Gy of irradiation and up to
      a dose of 60 Gy. The morphology was evaluated via scanning electron microscopy
      (SEM) (n = 8). The data were analyzed using a two-way analysis of variance
      (ANOVA) and Tukey's test (alpha = 5%). RESULTS: The enamel microhardness, as a
      whole, increased (p < 0.05) after a dose of 60 Gy (211.4 KH), mostly in the
      superficial enamel. There was a significant difference between the values of
      nonirradiated dentin microhardness (28.9 KH) compared with dentin that was
      irradiated with doses of 10 Gy (23.8 KH), 20 Gy (25.6 KH), 30 Gy (24.8 KH), and
      40 Gy (25.7 KH) (p < 0.05). There was no difference between nonirradiated dentin
      and dentin irradiated with 60 Gy (p > 0.05). The highest mean value of
      microhardness (29.9 KH) (p < 0.05) was found in the middle dentin. The groups
      that were irradiated with doses of 30 and 60 Gy exhibited greater surface changes
      in their enamel and dentin compared with the nonirradiated groups for all
      regions, exhibiting an amorphous surface upon increase of the irradiation doses.
      CONCLUSIONS: The enamel microhardness increased at a dose of 60 Gy, whereas the
      value of the dentin microhardness did not change. A progressive disruption of
      enamel and dentin morphology was found with the increased radiation dose.

PMID- 24450409
TI  - Patient satisfaction with HIV and TB treatment in a public programme in rural
      KwaZulu-Natal: evidence from patient-exit interviews.
AB  - BACKGROUND: Patient satisfaction is a determinant of treatment uptake, adherence
      and retention, and an important health systems outcome. Queues, health worker
      patient contact time, staff attitudes, and facility cleanliness may affect
      patient satisfaction. We quantified dimensions of patient satisfaction among HIV
      and TB patients in a rural sub-district of KwaZulu-Natal, South Africa, and
      identified underlying satisfaction factors that explained the data. METHODS: We
      conducted patient-exit interviews with 300 HIV and 300 TB patients who were
      randomly selected using a two-stage cluster random sampling approach with primary
      sampling units (primary healthcare clinics) selected with probability
      proportional-to-size sampling. We performed factor analysis to investigate
      underlying patient satisfaction factors. We compared the satisfaction with HIV
      and TB services and examined the relationships between patient satisfaction and
      patients' socio-demographic characteristics in multivariable regression. RESULTS:
      Almost all patients (95% HIV, 97% TB) reported to be globally satisfied with the
      healthcare services received on the day of the interview. However, patient
      satisfaction with specific concrete aspects of the health services was
      substantially lower: 52% of HIV and 40% of TB patients agreed that some staff did
      not treat patients with sufficient respect (p = 0.02 for difference between the
      two patient groups); 65% of HIV and 40% of TB patients agreed that health worker
      queues were too long (p < 0.001). Based on factor analysis, we identified five
      factors underlying the HIV data and the TB data (availability, accommodation,
      acceptability and communication for HIV and TB patients; health worker preference
      for HIV patients only; and global satisfaction for TB patients only). The level
      of satisfaction did not vary significantly with patients' socio-demographic
      characteristics. CONCLUSIONS: In this rural area, HIV and TB patients'
      evaluations of specific aspects of health services delivery revealed substantial
      dissatisfaction hidden in the global assessments of satisfaction. A wide range of
      patient satisfaction variables could be reduced to a few underlying factors that
      align broadly with concepts previously identified in the literature as affecting
      access to healthcare. Increases in health systems resources for HIV and TB, but
      also improvements in facility maintenance, staff attitudes and communication, are
      likely to substantially improve HIV and TB patients' satisfaction with the care
      they receive in public-sector treatment programmes in rural communities in South
      Africa.

PMID- 24450410
TI  - Patent foramen ovale is not associated with hypoxemia in severe chronic
      obstructive pulmonary disease and does not impair exercise performance.
AB  - RATIONALE: Patent foramen ovale (PFO) may be disadvantageous in chronic
      obstructive pulmonary disease (COPD). It is unknown whether right-to-left
      shunting through PFO increases during exercise impairing exercise performance.
      OBJECTIVES: To determine whether (1) PFO prevalence is greater in hypoxemic
      versus less hypoxemic patients with COPD, (2) PFO is associated with clinically
      relevant impairment, and (3) right-to-left shunting increases during exercise and
      impairs exercise performance. METHODS: Patients with COPD and age-matched control
      subjects underwent contrast transthoracic echocardiography and transcranial
      Doppler to identify PFO. Patients with COPD with no shunt and patients with large
      PFO underwent cardiopulmonary exercise tests with contrast transcranial Doppler,
      esophageal, and gastric balloon catheters. MEASUREMENTS AND MAIN RESULTS: PFO
      prevalence was similar in 50 patients with COPD and 50 healthy control subjects
      (46% vs. 30%; P = 0.15). Large shunts were more common in patients with COPD (26%
      vs. 6%; P = 0.01). In an expanded COPD cohort, PFO prevalence was similar in 31
      hypoxemic (Pao2 <= 7.3 kPa) and 63 less hypoxemic (Pao2 > 8.0 kPa) patients with
      COPD (39% vs. 52%; P = 0.27). Patients with intrapulmonary shunting had lower
      Pao2 than both patients with PFO and those with no right-to-left shunt (7.7 vs.
      8.6 vs. 9.3 kPa, respectively; P = 0.002). Shunting significantly increased
      during exercise in patients with COPD with PFO. Endurance time at 60% Vo2max was
      574 (178) seconds for patients with PFO and 534 (279) seconds for those without
      (P = ns). CONCLUSIONS: Hypoxemic patients with COPD do not have a higher
      prevalence of PFO. Patients with COPD with PFO do not perform less well either on
      a 6-minute walk or submaximal exercise testing despite increased right-to-left
      shunting during exercise.

PMID- 24450412
TI  - Synthesis, analgesic and anti-inflammatory activities of new methyl-imidazolyl
      1,3,4-oxadiazoles and 1,2,4-triazoles.
AB  - BACKGROUND: Long-term clinical employment of nonsteroidal anti-inflammatory drugs
      (NSAIDs) is associated with significant side effects including gastrointestinal
      (GI) lesions and kidney toxicity. In this paper we designed and synthesized new
      imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles by molecular hybridization of
      previously described anti-inflammatory compounds in the hope of obtaining new
      safer analgesic and anti-inflammatory agents. METHODS: The target structures were
      synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester
      5. The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H
      imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7
      15 according to the known procedures. In silico toxicity risk assessment and drug
      likeness predictions were done, in order to consider the privileges of the
      synthesized structures as drug candidates. RESULTS AND DISCUSSION: The analgesic
      and anti-inflammatory profile of the synthesized compounds were evaluated by
      writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9
      and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed
      significant anti-inflammatory response in comparison with control. Compounds 11
      and 13 were screened for their ulcerogenic activities and none of them showed
      significant ulcerogenic activity. The active Compounds 11 and 12 showed the
      highest drug likeness and drug score. CONCLUSIONS: The analgesic and anti
      inflammatory activities of title compounds were comparable to that of standard
      drug indomethacin with a safer profile of activity. The results revealed that
      both of oxadiazole and triazole scaffolds can be determined as pharmacophores.
      The in silico predictions and pharmacological evaluations showed that compounds
      11 and 12 can be chosen as lead for further investigations.

PMID- 24450411
TI  - Cardiovascular health in adolescents with type 1 diabetes: the SEARCH CVD study.
AB  - OBJECTIVE: In their Strategic Impact Goal Statement, the American Heart
      Association focused on primordial prevention of cardiovascular risk factors by
      defining metrics for ideal cardiovascular health (ICH). The prevalence of ICH
      among youth with type 1 diabetes is unknown. Youth with type 1 diabetes face an
      increased risk of cardiovascular disease (CVD) as they age. The purpose of this
      report was to examine the prevalence of ICH in a population of youth with type 1
      diabetes and to examine the association of ICH with measures of cardiovascular
      structure and function. RESEARCH DESIGN AND METHODS: This report is based on
      SEARCH CVD an ancillary study to the SEARCH for Diabetes in Youth. A total of 190
      adolescents with type 1 diabetes had complete data on all of the ICH metrics at
      baseline and had measures of arterial stiffness [pulse wave velocity (PWV),
      brachial distensibility (BrachD), and augmentation index (AIx)] and carotid
      intima-media thickness completed at a follow-up visit [on average 5 yr after
      baseline (interquartile range 4-5)]. RESULTS: No subjects met the ICH criteria
      for all 7 metrics. Meeting an increasing number of ICH metrics was significantly
      associated with lower arterial stiffness [lower PWV of the trunk (beta = -0.02 +/
      0.01; p = 0.004) and AIx (beta = -2.2 +/-0.66; p = 0.001), and increased BrachD
      (beta = 0.14 +/-0.07; p = 0.04)]. CONCLUSIONS: Increasing number of ICH metrics
      was significantly associated with decreased arterial stiffness, but prevalence of
      ICH in this population was low. Youth with type 1 diabetes could benefit from
      improvements in their cardiovascular health.

PMID- 24450413
TI  - Preterm birth by vacuum extraction and neonatal outcome: a population-based
      cohort study.
AB  - BACKGROUND: Very few studies have investigated the neonatal outcomes after vacuum
      extraction delivery (VE) in the preterm period and the results of these studies
      are inconclusive. The objective of this study was to describe the use of VE for
      preterm delivery in Sweden and to compare rates of neonatal complications after
      preterm delivery by VE to those found after cesarean section during labor (CS) or
      unassisted vaginal delivery (VD). METHODS: Data was obtained from Swedish
      national registers. In a population-based cohort from 1999 to 2010, all live
      born, singleton preterm infants in a non-breech presentation at birth, born after
      onset of labor (either spontaneously, by induction, or by rupture of membranes)
      by VD, CS, or VE were included, leaving a study population of 40,764 infants.
      Logistic regression analyses were used to calculate adjusted odds ratios (AOR),
      using unassisted vaginal delivery as reference group. RESULTS: VE was used in
      5.7% of the preterm deliveries, with lower rates in earlier gestations. Overall,
      intracranial hemorrhage (ICH) occurred in 1.51%, extracranial hemorrhage (ECH) in
      0.64%, and brachial plexus injury in 0.13% of infants. Infants delivered by VE
      had higher risks for ICH (AOR = 1.84 (95% CI: 1.09-3.12)), ECH (AOR = 4.48 (95%
      CI: 2.84-7.07)) and brachial plexus injury (AOR = 6.21 (95% CI: 2.22-17.4)),
      while infants delivered by CS during labor had no increased risk for these
      complications, as compared to VD. CONCLUSION: While rates of neonatal
      complications after VE are generally low, higher odds ratios for intra- and
      extracranial hemorrhages and brachial plexus injuries after VE, compared with
      other modes of delivery, support a continued cautious use of VE for preterm
      delivery.

PMID- 24450415
TI  - Advances in interventional pulmonology.
AB  - Interventional pulmonology (IP) remains a rapidly expanding and evolving
      subspecialty focused on the diagnosis and treatment of complex diseases of the
      thorax. As the field continues to push the leading edge of medical technology,
      new procedures allow for novel minimally invasive approaches to old diseases
      including asthma, chronic obstructive pulmonary disease and metastatic or primary
      lung malignancy. In addition to technologic advances, IP has matured into a
      defined subspecialty, requiring formal training necessary to perform the advanced
      procedures. This need for advanced training has led to the need for
      standardization of training and the institution of a subspecialty board
      examination. In this review, we will discuss the dynamic field of IP as well as
      novel technologies being investigated or employed in the treatment of thoracic
      disease. 

PMID- 24450414
TI  - 2-Methoxystypandrone inhibits signal transducer and activator of transcription 3
      and nuclear factor-kappaB signaling by inhibiting Janus kinase 2 and IkappaB
      kinase.
AB  - Constitutive activation of the signal transducer and activator of transcription 3
      (STAT3) or the nuclear factor-kappaB (NF-kappaB) pathway occurs frequently in
      cancer cells and contributes to oncogenesis. The activation of Janus kinase 2
      (JAK2) and IkappaB kinase (IKK) are key events in STAT3 and NF-kappaB signaling,
      respectively. We have identified 2-methoxystypandrone (2-MS) from a traditional
      Chinese medicinal herb Polygonum cuspidatum as a novel dual inhibitor of JAK2 and
      IKK. 2-MS inhibits both interleukin-6-induced and constitutively-activated STAT3,
      as well as tumor necrosis factor-alpha-induced NF-kappaB activation. 2-MS
      specifically inhibits JAK and IKKbeta kinase activities but has little effect on
      activities of other kinases tested. The inhibitory effects of 2-MS on STAT3 and
      NF-kappaB signaling can be eliminated by DTT or glutathione and can last for 4 h
      after a pulse treatment. Furthermore, 2-MS inhibits growth and induces death of
      tumor cells, particularly those with constitutively-activated STAT3 or NF-kappaB
      signaling. We propose that the natural compound 2-MS, as a potent dual inhibitor
      of STAT3 and NF-kappaB pathways, is a promising anticancer drug candidate.

PMID- 24450416
TI  - Patient navigator training in the Republic of the Marshall Islands.

PMID- 24450417
TI  - Metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides: a
      practical access to piperidine-fused bicyclic heterocycles.
AB  - The first metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides
      has been developed. With the use of a chiral ferrocenylphosphine-copper(I)
      complex as the catalyst, the asymmetric variant of the [6 + 3] cycloaddition has
      also been successfully achieved. The reactions proceeded smoothly under mild
      conditions, affording piperidine-fused bicyclic heterocycles in moderate to high
      yields with good to excellent diastereo- and enantioselectivies. The procedures
      are operationally simple and the catalysts are cheap and readily accessible, thus
      providing a practical approach to piperidine-fused bicyclic heterocycles. 

PMID- 24450418
TI  - Periodontal disease associated with red complex bacteria in dogs.
AB  - OBJECTIVE: Red complex bacteria (Treponema denticola, Tannerella forsythia and
      Porphyromonas gingivalis) play a major role in the aetiology of periodontal
      disease in humans. This study was designed to evaluate the association of such
      bacteria with periodontal disease in dogs. METHODS: Seventy-three subgingival
      samples taken from dogs ranging from 2 months to 12 years (median age 4 years)
      were tested for red complex bacteria using a polymerase chain reaction assay.
      RESULTS: Thirty-six of 73 (49 . 3%) dogs were found to be positive for T.
      forsythia and P. gingivalis. Dogs with gingivitis or periodontitis were more
      likely to be infected with T. forsythia and P. gingivalis [odds ratio (OR) 5 . 4
      (confidence interval (CI) 1 . 9-15 . 6), P = 0 . 002] than healthy animals. Only
      3 (4 . 1%) of 73 samples were positive for red complex bacteria, but the
      association with periodontal disease was not significant. CONCLUSION AND CLINICAL
      RELEVANCE: The results indicate that involvement of red complex bacteria in
      periodontal disease in dogs is similar to that observed in humans. Only the
      concurrent presence of T. forsythia and P. gingivalis were correlated to
      periodontal disease in dogs in this study.

PMID- 24450419
TI  - The pga gene cluster in Aggregatibacter actinomycetemcomitans is necessary for
      the development of natural competence in Ca(2+) -promoted biofilms.
AB  - Natural competence is the ability of bacteria to incorporate extracellular DNA
      into their genomes. This competence is affected by a number of factors, including
      Ca(2+) utilization and biofilm formation. As bacteria can form thick biofilms in
      the presence of extracellular Ca(2+) , the additive effects of Ca(2+) -promoted
      biofilm formation on natural competence should be examined. We evaluated natural
      competence in Aggregatibacter actinomycetemcomitans, an important periodontal
      pathogen, in the context of Ca(2+) -promoted biofilms, and examined whether the
      pga gene cluster, required for bacterial cell aggregation, is necessary for
      competence development. The A. actinomycetemcomitans cells grown in the presence
      of 1 mm CaCl2 exhibited enhanced cell aggregation and increased levels of cell
      associated Ca(2+) . Biofilm-derived cells grown in the presence of Ca(2+)
      exhibited the highest levels of natural transformation frequency and enhanced
      expression of the competence regulator gene, tfoX. Natural competence was
      enhanced by the additive effects of Ca(2+) -promoted biofilms, in which high
      levels of pga gene expression were also detected. Mutation of the pga gene
      cluster disrupted biofilm formation and competence development, suggesting that
      these genes play a critical role in the ability of A. actinomycetemcomitans to
      adapt to its natural environment. The Ca(2+) -promoted biofilms may enhance the
      ability of bacteria to acquire extracellular DNA. 

PMID- 24450420
TI  - Evidence for a potential protective effect of carnitine-pantothenic acid co
      treatment on valproic acid-induced hepatotoxicity.
AB  - Valproic acid is approved for treatment of seizures and manic episodes of bipolar
      disorder, and continues to be one of the most commonly prescribed antiepileptic
      drugs in the world. Hepatotoxicity is a rare but serious side effect resulting
      from its use, particularly in young patients. This adverse effect does not
      display normal dose-response curves and can be lethal in children. A review of
      the purported mechanisms of action suggest hepatotoxicity results from increased
      oxidative stress, caused by a reduction in beta-oxidation and an increase in
      activation of certain metabolizing enzymes. There is also evidence that both
      carnitine and pantothenic acid are involved in the regulation of valproic acid
      induced hepatotoxic processes, and clinical evidence has shown that treatment
      with either compound shows protective effects against hepatotoxicity. These
      results suggest a potential increase in protective effects with cotreatment of
      carnitine and pantothenic acid. 

PMID- 24450421
TI  - Oncological safety of autologous fat grafting after breast conservative
      treatment: a prospective evaluation.
AB  - Autologous fat graft to the breast is a useful tool to correct defects after
      breast conservative treatment (BCT). Although this procedure gains popularity,
      little is known about the interaction between the fat graft and the prior
      oncological environment. Evidences of safety of this procedure in healthy breast
      and after post-mastectomy reconstruction exist. However, there is paucity of data
      among patients who underwent BCT which are hypothetically under a higher risk of
      local recurrence (LR). Fifty-nine patients, with prior BCT, underwent 75
      autologous fat graft procedures using the Coleman's technique, between October
      2005 and July 2008. Follow-up was made by clinical and radiologic examination at
      least once, after 6 months of the procedure. Mean age was 50 +/- 8.5 years, and
      mean follow-up was 34.4 +/- 15.3 months. Mean time from oncological surgery to
      the first fat grafting procedure was 76.6 +/- 30.9 months. Most of patients were
      at initial stage 0 (11.8%), I (33.8%), or IIA (23.7%). Immediate complication was
      observed in three cases (4%). Only three cases of true LR (4%) associated with
      the procedure were observed during the follow-up. Abnormal breast images were
      present in 20% of the postoperative mammograms, and in 8% of the cases, biopsy
      was warranted. Autologous fat graft is a safe procedure to correct breast defects
      after BCT, with low postoperative complications. Although it was not associated
      with increased risk of LR in the group of patients studied, prospective trials
      are needed to certify that it does not interfere in patient's oncological
      prognosis.

PMID- 24450422
TI  - Capillary force-driven, large-area alignment of multi-segmented nanowires.
AB  - We report the large-area alignment of multi-segmented nanowires in nanoscale
      trenches facilitated by capillary forces. Electrochemically synthesized nanowires
      between 120 and 250 nm in length are aligned and then etched selectively to
      remove one segment, resulting in arrays of nanowires with precisely controlled
      gaps varying between 2 and 30 nm. Crucial to this alignment process is the
      dispersibility of the nanowires in solution which is achieved by chemically
      modifying them with hexadecyltrimethylammonium bromide. We found that, even
      without the formation of an ordered crystalline phase at the droplet edges, the
      nanowires can be aligned in high yield. To illustrate the versatility of this
      approach as a nanofabrication technique, the aligned nanowires were used for the
      fabrication of arrays of gapped graphene nanoribbons and SERS substrates. 

PMID- 24450423
TI  - Looking beyond discharge: clinical variables at trauma admission predict long
      term survival in the older severely injured patient.
AB  - BACKGROUND: Long term follow up is difficult to obtain in most trauma settings,
      these data are essential for assessing outcomes in the older (>=60) patient. We
      hypothesized that clinical data obtained during initial hospital stay could
      accurately predict long term survival. STUDY DESIGN: Using our trauma registry
      and hospital database, we reviewed all trauma admissions (age >=60, ISS > 15) to
      our Level 1 center over the most recent 7 years. Mechanism of injury, co
      morbidities, ICU admission, and ultimate disposition were assessed for 2-7 years
      post-discharge. Primary outcome was defined as long term survival to the end of
      the last year of the study. RESULTS: Of 342 patients discharged following initial
      admission, mean age was 76.2 +/- 9.7, and ISS was 21.5 +/- 6.9. 119 patients
      (34.8%) died (mean follow up 18.8 months; range 1.1-66.2 months). For 233
      survivors, mean follow-up was 50.2 months (range 24.8-83.8 months). Univariate
      analysis disclosed post-discharge mortality was associated with age (80.1 +/-
      9.64 vs. 74.2 +/- 9.07), mean number of co-morbidities (1.6 +/- 1.1 vs. 1.0 +/-
      1.2), fall as a mechanism, lower GCS upon arrival (11.85 +/- 4.21 vs. 13.73 +/-
      2.89), intubation at the scene and discharge to an assisted living facility (p <
      0.001 for all). Cox regression analysis hazard ratio showed that independent
      predictors of mortality on long term follow-up included: older age, fall as
      mechanism, lower GCS at admission and discharge to assisted living facility (all
      = p < 0.0001). CONCLUSIONS: Nearly two-thirds of patients >=60 who were severely
      injured survived >4 years following discharge; furthermore, admission data,
      including younger age, injury mechanism other than falls, higher GCS and home
      discharge predicted a favorable long term outcome. These findings suggest that
      common clinical data at initial admission can predict long term survival in the
      older trauma patient.

PMID- 24450424
TI  - Enzymatic formation of PEGylated oligonucleotides.
AB  - Gene therapy, siRNA, and therapeutic aptamers attract great interest owing to
      their versatility to treat a wide range of diseases and their potential high
      selectivity. Unfortunately, oligonucleotide-based therapeutics suffer rapid
      degradation by nucleases, scarce cell internalization, and fast kidney clearance.
      To address these limitations, the covalent attachment by mild chemical reactions
      of an activated polyethylene glycol (PEG) is widely used to obtain PEGylated
      nucleic acids showing a more favorable pharmacokinetic profile. We describe here
      a method for the enzymatic formation of PEGylated nucleic acids employing T4 DNA
      ligase: the ligation protocol was set up and optimized allowing the complete
      achievement of PEGylated oligonucleotides amenable to further enzymatic
      reactions. The feasibility of this approach for bioconjugation was demonstrated
      employing a set of PEG-donors and oligonucleotide acceptors, differing in the
      chemical link between PEG and the oligonucleotide donor, and in the length,
      sequence, and structure of the oligonucleotides employed. The ligase reaction
      allowed us to obtain double-stranded as well as single-stranded oligonucleotides,
      thus demonstrating the applicability of the method to a variety of substrates
      suitable for diagnostic and therapeutic applications. 

PMID- 24450425
TI  - Filter-aided N-glycan separation (FANGS): a convenient sample preparation method
      for mass spectrometric N-glycan profiling.
AB  - We have developed a simple method for the release and isolation of glycoprotein N
      glycans from whole-cell lysates using less than a million cells, for subsequent
      implementation with mass spectrometric analysis. Cellular protein extracts
      prepared using SDS solubilization were sequentially treated in a membrane filter
      device to ultimately release glycans enzymatically using PNGase F in the volatile
      buffer ammonium bicarbonate. The released glycans are recovered in the filtrate
      following centrifugation and typically permethylated prior to mass spectrometric
      analysis. We call our method "filter-aided N-glycan separation" and have
      successfully applied it to investigate N-glycan profiles of wild-type and mutant
      Chinese hamster ovary cells. This method is readily multiplexed and, because of
      the small numbers of cells needed, is compatible with the analysis of replicate
      samples to assess the true nature of glycan variability in tissue culture
      samples. 

PMID- 24450426
TI  - Characteristics and the trajectory of psychotropic medication use in general and
      antipsychotics in particular among adults with an intellectual disability who
      exhibit aggressive behaviour.
AB  - BACKGROUND: A high proportion of adults with an intellectual disability (ID) are
      known to receive psychotropic medications for the management of aggressive
      behaviour in the absence of any psychiatric diagnosis. Despite this widespread
      use of psychotropic medication in general and antipsychotic medication in
      particular, no study has reported the trajectory of psychotropic medication use
      using a prospective design. METHOD: We have prospectively studied a community,
      clinic-based sample of 100 adults with ID and aggressive behaviour over a 6-month
      period for use of psychotropic medication in general and antipsychotics in
      particular, and compared them with demographic, psychiatric and behavioural
      variables. RESULTS: Psychotropic medications were used for 89% of patients at
      baseline (T1) and 90% at 6 months' (T2) follow-up. Risperidone was the most
      commonly used antipsychotic medication followed by chlorpromazine, haloperidol,
      olanzapine, zuclopenthixol and quetiapine. Other commonly used medications were
      SSRI antidepressants such as citalopram, paroxetine and fluoxetine followed by
      mood stabilisers such as carbamazepine and sodium valproate. Although in a high
      proportion of cases carbamazepine and sodium valproate were used to treat
      epilepsy per se. A high proportion (45%) received more than one (polypharmacy)
      psychotropic medication at T1; however, this proportion decreased slightly to 41%
      at T2. As for antipsychotic prescribing specifically, a similar proportion
      received them at T1 (75%) and T2 (73%), with polypharmacy of antipsychotics
      remaining similar at T1 (10%) and at T2 (9%). Twenty-three per cent and 20% of
      patients received over 300 mg/day of chlorpromazine equivalent dose of
      antipsychotics at T1 and T2 respectively. However, there was an overall
      significant reduction in the severity of aggressive behaviour between T1 and T2.
      Higher doses of antipsychotic prescribing were positively correlated with more
      severe aggressive behaviour, physical aggression towards objects, self-injurious
      behaviour and increasing age. There was no significant association with other
      demographic variables, physical health conditions or psychiatric diagnosis.
      Neither was there any significant correlation between mean aggression severity
      score change and antipsychotic daily dose change between T1 and T2. CONCLUSIONS:
      To our knowledge, this is the first ever comprehensive follow-up study of use of
      psychotropic medications in general but antipsychotics in particular over a 6
      month period in adults with ID and aggressive behaviour, in a clinic-based
      community setting which also compared the trajectory of severity of aggressive
      behaviour with that of antipsychotic medication dose. Our study shows that not
      only the use of psychotropic medication is common among adults with ID who attend
      psychiatric clinics for aggressive behaviour, the use of polypharmacy of
      psychotropic medications in general and high dose of antipsychotics in particular
      are equally prevalent. However, in some cases two antipsychotics may have been
      prescribed simultaneously as the psychiatrist is in the process of switching from
      one to another.

PMID- 24450427
TI  - Follow-up study of lympho-histiocytic villitis and incidental retroplacental
      hematoma.
AB  - Placentas are usually submitted for pathologic examination based on obstetrical
      indications. We hypothesized that the placenta may have diagnostic value to the
      infant independent of obstetrical events. We specifically tested whether
      lymphohistiocytic villitis (noninfectious) would predict autoimmune or alloimmune
      disease based on transfer of activated maternal T-cells to the fetus and whether
      clinically silent placental separations (retroplacental hematomas, RPH) would
      predict neurologic injury in the infant. All placentas from consecutive
      deliveries had a routine pathologic examination of the placenta. The infants with
      placentas demonstrating inflammation of >1% of villi or RPH >2 cm and matched
      controls had their hospital charts reviewed and parental interviews by telephone
      at 5 to 7 years of age. The children of consented patients were also searched for
      in the office visits of the University of Louisville Pediatric Neurology and
      Rheumatology divisions. One thousand six hundred eighty-four patients consented
      to the follow-up study. We found no cases of autoimmune disease among 17 children
      with villitis >1%. Of 16 infants with RPH, 1 had cerebral palsy but with other
      placental findings, 1 had lethal hydranenecephaly, and the remainder had no
      adverse outcome. Of 15 children seen by a pediatric neurologist, none had the
      same placental lesion. The specific lesions of lymphohistiocytic villitis or
      asymptomatic RPH do not predict significant pediatric disease by 7 years of age.
      At least for these 2 lesions, the placenta does not have diagnostic value to the
      infant.

PMID- 24450429
TI  - Genotyping of Pseudomonas aeruginosa isolates from lung transplant recipients and
      aquatic environment-detected in-hospital transmission.
AB  - Lung infection with Pseudomonas aeruginosa is common in lung transplant
      recipients and may lead to severe complications. Bacteriological surveillance
      aims to detect transmission of microbes between hospital environment and
      patients. We sought to determine whether genotyping of P. aeruginosa isolates
      could improve identifications of pathways of infection. From 2004 to 2009, we
      performed genotyping with multiple-locus variable number of tandem repeats
      analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) of P. aeruginosa
      isolates cultured from lung transplant recipients at Sahlgrenska University
      Hospital, Gothenburg. During a small outbreak in 2008, cultivation and genotyping
      of isolates from sink and drains samples from the hospital ward were performed.
      Pseudomona aeruginosa from 11/18 patients were genotyped to unique strains. The
      remaining seven patients were carriers of a P. aeruginosa strain of cluster A
      genotype. Pseudomona aeruginosa was isolated in 4/8 water samples, typed by MLVA
      also as cluster A genotype and confirmed by PFGE to be similar or identical to
      the isolates from four transplanted patients. In conclusion, genotyping of
      isolates revealed a clonal relationship between patient and water isolates,
      indicating in-hospital transmission of P. aeruginosa. We suggest genotyping with
      MLVA for rapid routine surveillance, with the PFGE method used for extended,
      confirmatory analyses. 

PMID- 24450432
TI  - Bacillus thuringiensis Cry6A exhibits nematicidal activity to Caenorhabditis
      elegans bre mutants and synergistic activity with Cry5B to C. elegans.
AB  - The group of nematicidal crystal protein Cry6A shares very low identity and
      exhibits different structure with Cry5B, another well-studied group of
      nematicidal crystal protein produced by Bacillus thuringiensis. In this study, we
      assayed the susceptibility of bre mutants (Caenorhabditis elegans with resistance
      to Cry5B) to Cry6Aa2 and examined the synergistic activity between Cry6Aa2 and
      Cry5Ba2. Our results show that all bre mutants are susceptible to Cry6Aa2 on the
      lethal activity, growth inhibition, fertility and exhibit no cross-resistance to
      Cry6Aa2. Moreover, all combinations of Cry6Aa2 and Cry5Ba2 with serial ratios
      exhibit significant synergism to C. elegans, and the highest synergistic effect
      was observed when Cry6Aa2 and Cry5Ba2 were mixed with a ration of 4 : 1. The
      susceptibility of bre mutants to Cry6A and synergistic activity between Cry6A and
      Cry5B may be attributed to the diverse action mode, because of different
      structure of the two nematicidal crystal protein toxins. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Bacillus thuringiensis nematicidal crystal proteins Cry6A and Cry5B
      share notable structural differences. Our study confirmed that there is no cross
      resistance of Caenorhabditis elegans bre mutants (with resistance to Cry5B) to
      Cry6A, and combination of Cry6A and Cry5B shows synergistic activity against C.
      elegans. This result provides a more effective strategy for biocontrol of plant
      parasitic nematodes using a combination of Cry6A and Cry5B. Combination of Cry6A
      and Cry5B could enhance nematicidal toxicity of Bt and supply an alternative to
      overcome the potential resistance of plant-parasitic nematodes when large-scale
      and long-term use of Bt toxins.

PMID- 24450433
TI  - Elucidating influenza inhibition pathways via network reconstruction.
AB  - Viruses evade detection by the host immune system through the suppression of
      antiviral pathways. These pathways are thus obscured when measuring the host
      response to viral infection and cannot be inferred by current network
      reconstruction methodology. Here we aim to close this gap by providing a novel
      computational framework for the inference of such inhibited pathways as well as
      the proteins targeted by the virus to achieve this inhibition. We demonstrate the
      power of our method by testing it on the response to influenza infection in
      humans, with and without the viral inhibitory protein NS1, revealing its direct
      targets and their inhibitory effects.

PMID- 24450435
TI  - Safety concerns to application of graphene compounds in pharmacy and medicine.
AB  - Graphene, the new allotrope of carbon is a single layer of monocrystalline
      graphite with sp2 hybridized carbon atoms. This compound has received worldwide
      attention due to its extraordinary physical and chemical properties. Duo to the
      widespread application of geraphenes, concerns are raising about its
      environmental safety or the safety protocols for handling and waste of graphene
      based materials. The generation of reactive free radicals, adsorption of
      important biomolecules, and physical toxicity of graphene also matter. Hereby we
      criticize the concerns on the toxicity of graphenes to provide some perspective
      on the potential hazards of future development in graphene-based biomaterials. 

PMID- 24450434
TI  - Development of a genetic system for the deep-sea psychrophilic bacterium
      Pseudoalteromonas sp. SM9913.
AB  - BACKGROUND: Pseudoalteromonas species are a group of marine gammaproteobacteria
      frequently found in deep-sea sediments, which may play important roles in deep
      sea sediment ecosystem. Although genome sequence analysis of Pseudoalteromonas
      has revealed some specific features associated with adaptation to the extreme
      deep-sea environment, it is still difficult to study how Pseudoalteromonas adapt
      to the deep-sea environment due to the lack of a genetic manipulation system. The
      aim of this study is to develop a genetic system in the deep-sea sedimentary
      bacterium Pseudoalteromonas sp. SM9913, making it possible to perform gene
      mutation by homologous recombination. RESULTS: The sensitivity of
      Pseudoalteromonas sp. SM9913 to antibiotic was investigated and the erythromycin
      resistance gene was chosen as the selective marker. A shuttle vector pOriT-4Em
      was constructed and transferred into Pseudoalteromonas sp. SM9913 through
      intergeneric conjugation with an efficiency of 1.8 * 10-3, which is high enough
      to perform the gene knockout assay. A suicide vector pMT was constructed using
      pOriT-4Em as the bone vector and sacB gene as the counterselective marker. The
      epsT gene encoding the UDP-glucose lipid carrier transferase was selected as the
      target gene for inactivation by in-frame deletion. The epsT was in-frame deleted
      using a two-step integration-segregation strategy after transferring the suicide
      vector pMT into Pseudoalteromonas sp. SM9913. The DeltaepsT mutant showed
      approximately 73% decrease in the yield of exopolysaccharides, indicating that
      epsT is an important gene involved in the EPS production of SM9913. CONCLUSIONS:
      A conjugal transfer system was constructed in Pseudoalteromonas sp. SM9913 with a
      wide temperature range for selection and a high transfer efficiency, which will
      lay the foundation of genetic manipulation in this strain. The epsT gene of
      SM9913 was successfully deleted with no selective marker left in the chromosome
      of the host, which thus make it possible to knock out other genes in the same
      host. The construction of a gene knockout system for Pseudoalteromonas sp. SM9913
      will contribute to the understanding of the molecular mechanism of how
      Pseudoalteromonas adapt to the deep-sea environment.

PMID- 24450436
TI  - The use of self-expandable metallic stents in the airways in the adult
      population.
AB  - The airway stents restore patency in the face of luminal compromise from
      intrinsic and/or extrinsic pathologies. Luminal compromise beyond 50% often leads
      to debilitating symptoms such as dyspnea. Silicone stents remain the most
      commonly placed stents worldwide and have been the "gold standard" for the
      treatment of benign and malignant airway stenoses over the past 20 years.
      Nevertheless, silicone stents are not the ideal stents in all situations.
      Metallic stents can serve better in some selected conditions. Unlike silicone
      stents, there are large and increasing varieties of metallic stents available on
      the market. The lack of prospective or comparative studies between various types
      of metallic stents makes the choice difficult and expert-opinion based.
      International guidelines are sorely lacking in this area. 

PMID- 24450437
TI  - Women's views and experiences of antenatal care in Iraq: a Q methodology study.
AB  - BACKGROUND: Understanding women's experiences and perspectives of antenatal care
      services is particularly critical for enhancing effectiveness of services
      delivery and addressing women's needs and expectations. As part of a
      comprehensive assessment of the maternity care services in Iraq, this study aimed
      to explore the views and experiences of antenatal care in a sample of women.
      METHODS: This explorative study was conducted in Erbil governorate, Iraq. Data
      were collected using Q methodology, a technique for eliciting subjective views
      and identifying shared patterns among individuals. A sample of 38 women of
      different educational and socioeconomic statuses were invited to sort a set of 39
      statements reflecting different aspects of the available antenatal care services
      and issues related to their last pregnancies into a distribution on a scale of
      nine from "disagree most" to "agree most". By-person factor analysis was used to
      derive latent views through centroid factor extraction and varimax rotation of
      factors. RESULTS: Analysis of the participants' Q sorts resulted in identifying
      four distinct views and experiences of pregnancy and antenatal care services: (i)
      public maternity services second best: preference for, and ability to afford,
      private care, (ii) dissatisfaction with public maternity services: poor
      information sharing and lack of health promotion, (iii) satisfaction with public
      maternity service but information gaps perceived and (iv) public maternity
      services second best: preference for private care but unaffordable. The typical
      characterizations that were associated with each view were highlighted.
      CONCLUSIONS: This study revealed different patterns of views and experiences of
      women of pregnancy and antenatal care services and recognized the particular
      issues related to each pattern. Different patterns and types of problems and
      concerns related mainly to inadequate provision of information and poor
      interpersonal communication, poor utilization of public services and a general
      preference to use private services were identified in the different groups of
      women.

PMID- 24450438
TI  - Targeting the hedgehog-glioma-associated oncogene homolog pathway inhibits
      bleomycin-induced lung fibrosis in mice.
AB  - Idiopathic pulmonary fibrosis has been associated with the reactivation of
      developmental pathways, notably the Hedgehog-Glioma-associated oncogene homolog
      (GLI) pathway. In this study, we determined whether the Hedgehog pathway was
      activated in bleomycin-induced lung injury in mice, and whether targeting the
      Hedgehog-Gli pathway could decrease bleomycin-induced lung fibrosis. After
      intratracheal injection of bleomycin on Day 0, C57Bl6 mice received GDC-0449 (an
      inhibitor of Smoothened, the transducer of the pathway), or 2,2'-[[Dihydro-2-(4
      pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N dimethylbenzenamine
      (GANT61; an inhibitor of GLI transcription factors in the nucleus), from Day 7 to
      Day 13. At Day 14, whole-lung homogenates were obtained for morphological
      analysis, assessment of cell apoptosis and proliferation, collagen
      quantification, and evaluation of profibrotic (transforming growth factor-beta,
      connective tissue growth factor, plasminogen activator inhibitor 1, vascular
      endothelial growth factor-A) and proinflammatory mediators (IL-1beta) expression.
      We showed that the Hedgehog pathway was activated in bleomycin-induced lung
      fibrosis on Day 14 after injury, with an increased lung expression of the ligand,
      Sonic Hedgehog, and with increased messenger RNA expression and nuclear
      localization of GLI1 and GLI2. Inhibition of Smoothened with GDC-0449 did not
      influence the development of bleomycin-induced lung fibrosis. By contrast, the
      inhibition of GLI activity with GANT61 decreased lung fibrosis and lung collagen
      accumulation, and promoted an antifibrotic and anti-inflammatory environment. Our
      results identify the hedgehog-Gli pathway as a profibrotic pathway in
      experimental fibrosis. Inhibition of the Hedgehog-Gli pathway at the level of GLI
      transcriptional activity could be a therapeutic option in fibrotic lung diseases.

PMID- 24450439
TI  - Management and complications of anaesthesia during balloon valvuloplasty for
      pulmonic stenosis in dogs: 39 cases (2000 to 2012).
AB  - OBJECTIVES: The aim of this study was to report the management and complications
      of anaesthesia in dogs undergoing balloon valvuloplasty. METHODS: A retrospective
      review of medical records of dogs that were diagnosed with pulmonic stenosis and
      undergoing balloon valvuloplasty between 2000 and 2012. RESULTS: Thirty-nine
      cases were identified (28 males and 11 females). Median (range) age and
      bodyweight was 6 (4 to 48) months and 11.5 (2.0 to 30.3) kg, respectively. The
      most commonly represented breeds included mixed breed (n = 7, 17.9%) and English
      bulldog (n = 6, 15.3%). Anaesthesia was induced most commonly with intravenous
      administration of ketamine-diazepam (n = 8, 20.5%), propofol-diazepam (n = 8,
      20.5%), or propofol-midazolam-lidocaine (n = 6, 15.4%), and maintained with
      isoflurane in combination with fentanyl or lidocaine. Anaesthetic and surgery
      times (mean +/- sd) were 268.5 +/-54 minutes and 193.2 +/-50 minutes,
      respectively. The most common intraoperative complications were hypotension (n =
      19, 48.7%), bradycardia (n = 8, 20.5%) and desaturation (n = 7, 17.9%). Cardiac
      arrhythmias were observed in 21 (53.8%) dogs. Death occurred in one (2.6%) dog
      due to severe hypotension after ballooning followed by cardiac arrest. CLINICAL
      SIGNIFICANCE: Successful anaesthesia can be performed in young dogs with pulmonic
      stenosis undergoing balloon valvuloplasty. Management of anaesthesia requires
      intense monitoring and immediate treatment of complications. Anaesthetic risk
      increases during ballooning and may result in cardiac arrest.

PMID- 24450441
TI  - Plasticity in latitudinal patterns of leaf N and P of Oryza rufipogon in China.
AB  - Characterising the adaptability in nature of plant stoichiometric patterns across
      geographic or environmental gradients is important in advancing our understanding
      of the organisation of plant-nutrient relationships. We examined correlations
      between plant nutrient traits, latitude, longitude, climate and soil variables in
      34 populations of Oryza rufipogon across its range. We further compared the
      responses of population transplants at two experimental gardens: one beyond its
      northern natural range and another near the southern limit, to assess the nature
      of geographic variation in plant nutrients. The study showed that leaf P of O.
      rufipogon in the field was negatively correlated with latitude and largely
      depended on temperature and soil P availability. Leaf N was not related to
      latitude but was significantly correlated with precipitation and soil N
      concentration. Leaf N:P ratio was largely determined by absorption efficiency of
      P. Transplantation revealed that there were no significant associations of leaf
      nutrients with geographic, climatic or soil variables of origin in either of the
      experimental gardens, indicating phenotypic plasticity. However, examination of
      relationships between response ratios of leaf nutrients and change ratio of
      climate and soil environments, as well as norms of reaction in the
      transplantation experiment, revealed more complexity, suggesting both substantial
      genotypic diversity and the existence of genotype * environment interactions in
      these populations of O. rufipogon. These data indicate that adaptive plasticity
      response of plants to temperature and soil P availability significantly explain
      the observed shifts in leaf N, P and N:P of O. rufipogon along latitudinal
      gradients. 

PMID- 24450440
TI  - Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for
      cancer: lack of vascular normalization.
AB  - Photodynamic therapy (PDT) is an effective clinical treatment for a number of
      different cancers. PDT can induce hypoxia and inflammation, pro-angiogenic side
      effects, which may counteract its angio-occlusive mechanism. The combination of
      PDT with anti-angiogenic drugs offers a possibility for improved anti-tumour
      outcome. We used two tumour models to test the effects of the clinically approved
      angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in
      combination with PDT, and compared these results with the effects of bevacizumab,
      the anti-VEGF antibody, for the improvement of PDT. Best results were obtained
      from the combination of PDT and low-dose axitinib or sorafenib. Molecular
      analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR-2
      expression in tumour vasculature. Treatment with bevacizumab, although effective
      as monotherapy, did not improve PDT outcome. In order to test for tumour vessel
      normalization effects, axitinib was also applied prior to PDT. The absence of
      improved PDT outcome in these experiments, as well as the lack of increased
      oxygenation in axitinib-treated tumours, suggests that vascular normalization did
      not occur. The current data imply that there is a future for certain anti
      angiogenic agents to further improve the efficacy of photodynamic anti-cancer
      therapy. 

PMID- 24450442
TI  - Three different situations and approaches in the management for anomalous origin
      of the right coronary artery from the left coronary sinus: case report.
AB  - Anomalous origin of the right coronary artery from the left coronary sinus is
      rare but potentially dangerous if any ischemic signs are present. Multiple
      therapeutic options were advocated so far. We experienced three different
      situations and surgical approaches to these anomalies, and reviewed
      retrospectively. For the first case, we made a neo-ostium on the right sinus of
      Valsalva and anastomosed with the right coronary artery after arteriotomy. For
      the second and third cases, we applied coronary artery bypasses emergently:
      patient 2 the gastroepiploic artery during off-pump coronary artery bypass and
      patient 3 the left internal thoracic artery during surgery for acute aortic
      dissection. For the better outcomes, it is important to understand anatomic and
      hemodynamic characteristics of each patient and select the surgical options
      considering each characteristic. 

PMID- 24450443
TI  - Breast cancer in young women - lessons from an institutional review.

PMID- 24450444
TI  - Early versus later response to treatment in patients with community-acquired
      pneumonia: analysis of the REACH study.
AB  - BACKGROUND: Key goals in the treatment of CAP include early response to treatment
      and achievement of clinical stability. The US FDA recommends early response
      endpoints (72 hours after initiation of treatment) in clinical trials for the
      treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study
      to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated
      Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a
      retrospective observational study, providing current data on the clinical
      management and resource burden of CAP in real-life settings in European
      hospitals. This analysis reviews the characteristics and outcomes of patients
      showing early positive response to treatment (time to clinical stability [TCS]
      <=4 days, as assessed by Halm's criteria) compared with patients with later
      positive response (TCS >4 days). METHODS: Patients were adults, hospitalized with
      CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics.
      RESULTS: Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by
      Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253
      (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's
      criteria varied across participating countries, ranging from 0% (Belgium) to
      49.1% (UK). Patient characteristics and relevant medical history were similar
      between the two groups. There were no notable differences in initial antibiotic
      therapy between groups, except that more early responders had been treated with
      amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively)
      than later responders (5.9%; 1.2%, respectively). Initial treatment modification
      and re-infection or recurrences were less frequent in early responders compared
      with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early
      responders had a shorter duration of hospitalization (mean 9.4 +/- SD 7.0; median
      8.0 days vs. mean 15.6 +/- SD 10.5; median 12.0 days, respectively), lower rate
      of ICU admission (3.3% vs. 21.3%) and shorter duration of ICU stay (mean 6.2 +/-
      SD 5.7; median 4.0 days vs. mean 10.4 +/- SD 10.1; median 8.0 days, respectively)
      compared with later responders. Mortality was low in both groups. CONCLUSIONS:
      Achieving early clinical stabilization in CAP (<=4 days) is associated with
      improved outcomes, lower requirement for initial treatment modification or
      readmission and lower resource use, compared with a later response. TRIAL
      REGISTRATION: NCT01293435.

PMID- 24450446
TI  - Clinical pharmacologists in pharmacoeconomics: what is their role?
AB  - Clinical pharmacologists have three distinct contributions to make in the
      economic evaluation of new and existing pharmaceutical products: they should play
      a significant role in promoting the principles of "opportunity costs" in
      healthcare; they need to have a broad understanding of the methodology of
      economic evaluation in healthcare; they have a critical role in bringing their
      specialist knowledge, skills and experience in decision-making. In fulfilling
      these essential roles clinical pharmacologists may find themselves outside their
      conventional "comfort zones". Nevertheless, clinical pharmacologists need to rise
      to the occasion if they are to meet their obligations to patients and to society
      as a whole. 

PMID- 24450445
TI  - Increased risk of cancer in patients with early-onset cataracts: a nationwide
      population-based study.
AB  - Early-onset cataracts are associated with insufficient antioxidative activity,
      and, therefore, a potential risk of cancer. This study investigated the risk of
      cancer after being diagnosed with early-onset cataracts. Retrospective claims
      data from the Taiwan National Health Insurance Research Database were analyzed.
      Study subjects were comprised of patients with early-onset cataracts, aged 20-55
      years (International Classification of Diseases, 9th Revision, Clinical
      Modification [ICD-9-CM] code 366.00, 366.01, 366.02, 366.03, 366.04, 366.09,
      366.17 and 366.18) and newly diagnosed between 1997 and 2010 (n = 1281), and a
      comparison cohort without the disease (n = 5124). Both cohorts were followed up
      until 2010 to estimate the incidences of cancer. We used the Poisson regression
      model to compare incidence rate ratios and the 95% confidence interval (CI). Cox
      proportional hazards regression was used to assess the hazard ratio (HR) of
      cancer associated with early-onset cataracts. The overall incidence rate of all
      cancers was 2.19-fold higher in the early-onset cataract cohort than in the
      comparison cohort (8.06 vs 3.68 per 1000 person-years) with an adjusted HR of
      2.13 (95% CI = 1.48, 3.07). The site-specific analysis also showed a strong
      relationship, with adjusted HR of 3.24 ((95% CI = 1.30, 8.10) for head and neck
      cancer, 3.29 (95% CI 1.16, 9.31) for hepatoma and 3.19 (95% CI 1.34, 7.58) for
      breast cancer. The present study suggests that patients with early-onset
      cataracts are at an increased risk of being diagnosed with cancer in subsequent
      years.

PMID- 24450447
TI  - Comment on "Changes in droplet surface tension affect the observed hygroscopicity
      of photochemically aged biomass burning aerosol".

PMID- 24450448
TI  - Research experience with a person going through the process of dying and death.

PMID- 24450449
TI  - Reintroduction of cow's milk in milk-allergic children.
AB  - Even though cow's milk protein allergy (CMPA) is one of the most common food
      allergies in childhood, its prognosis is generally good and cow's milk (CM) is
      usually reintroduced in the patient's diet. The natural history of CMPA shows
      heterogeneity and is closely related to the immunological and clinical phenotype
      by which CMPA presents. Children with non-IgE-mediated CMPA tend to develop
      tolerance at an earlier age and at a higher percentage compared to those with IgE
      mediated disease. In subjects with severe symptoms CMPA may persist for longer or
      ever. Although, the majority of children will outgrow their allergy, the
      individual timing of tolerance acquisition is largely unknown. Most of the
      current guidelines on the diagnosis and management of CMPA suggest reevaluation
      of milk-allergic children every 6-12 months, and reintroduction of CM after a
      negative Oral Food Challenge (OFC). However, OFC procedure is time consuming,
      expensive and not without risk. Clinical variables and the measurements of sIgE
      levels and SPT wheal sizes to crude (whole) CM protein and individual milk
      protein components may provide some useful prognostic information in the course
      of CMPA. However, no clear-cut clinical or laboratory criteria exist to predict
      which children and at what age are more likely to pass a repeat (reintroduction)
      OFC. The identification of factors that could accurately predict the outcome of
      reintroduction OFC and the timing of tolerance development would be extremely
      useful in daily clinical practice. Until recently, reintroduction of CM was
      commonly attempted when children with CMPA were more likely to have become
      tolerant. Over the last years, a different approach in the management of milk and
      egg allergy has emerged with specific oral tolerance induction (SOTI) as a
      promising method for the treatment of food allergies. Furthermore, a number of
      studies have shown evidence that introduction of heated milk and egg protein into
      the diet of allergic patients may induce the acquisition of tolerance. Still, the
      question of when and how to reintroduce cow's milk in milk-allergic children
      remains challenging and further research in this important field is necessary to
      provide both clinicians and anxious parents with the desirable answer.

PMID- 24450450
TI  - Refractory proctocolitis in the exclusively breast-fed infants.
AB  - The arm of this review was to help general pediatricians and primary care
      physicians in diagnosing and managing cow's milk protein allergy in exclusively
      breast-fed infants. Allergic proctocolitis is a cause of rectal bleeding in
      exclusively breast-fed infants aged from 1 to 6 months.It is due to cow's milk
      protein transferred via breast milk. Diagnosis is based on clinical features and
      recovery after dietetic therapy. Rectal bleeding generally resolves within 72-96
      hours of cow's milk protein maternal avoidance. Most infants tolerate cow's milk
      by their first birthday. 

PMID- 24450451
TI  - Cow's milk allergy in children, from avoidance to tolerance.
AB  - Food allergy is the primary cause of anaphylaxis in paediatric age affecting
      roughly 4% of children and their families worldwide, and requiring changes in
      dietary habits. The prognosis for food allergy in children has traditionally been
      regarded as good for the most frequent allergens, however the prognosis for cow's
      milk allergy in the pediatric age is currently considered to be worse than
      previously believed. There is now enough evidence that measures of avoidance for
      children at risk did not have any preventive effect whatsoever, but they still
      came to be counterproductive by avoiding the physiological interaction between
      food allergens and gastrointestinal mucosal immune system. Programs of specific
      oral tolerance induction (SOTI) have obtained interesting results in the
      treatment of food allergy supporting the idea that antigen exposure through
      gastrointestinal section is important to allow the development of tolerance.
      Nevertheless this approach is not yet considered "ready" for community
      recommendations. In this paper we describe our experience in the field of SOTI in
      children with cow's milk allergy. 

PMID- 24450452
TI  - Breast-milk characteristics protecting against allergy.
AB  - Breast milk and colostrum are the first feeding sources for a child, providing
      nutrients, growth factors and immunological components, which are crucial for the
      newborn's correct development and health. Length of exclusive breastfeeding and
      time of solid foods introduction is a key factor that may influence allergy
      development. There is an emerging evidence of a relationship between
      breastfeeding, milk composition and lower risk of chronic diseases, such as
      diabetes, obesity, hypertension and allergies. This review examines current
      evidence regarding humoral and cellular characteristics of breast-milk, and
      potential role of environment, maternal diet and breastfeeding on the allergy
      development in children. 

PMID- 24450453
TI  - Soy- and rice-based formula and infant allergic to cow's milk.
AB  - Soy milk formula has limited medical indications for infants feeding, although in
      several parts of the world it has been used as a source of nutrition in a large
      number of children. It used to be the main alternative feeding for infants
      allergic to cow's milk who did not breastfeed before the introduction of
      extensively hydrolyzed formulas. Although there is a debate, the fact that some
      children are allergic to soy or some children with cow's milk allergy can present
      with concomitant soy allergy, restricted the use of soy formulas for treatment of
      infants allergic to cow's milk. Other grain-based formulas like the rice-based
      ones are promising in infants with cow's milk allergy. Grain-based formulas could
      be an alternative and cheaper way of nutrition for infants allergic to cow's milk
      than extensively hydrolyzed formulas. Further large scale longitudinal clinical
      studies are required to clarify the safety of soy and other grain-based formulas
      for treatment of cow's milk allergy.

PMID- 24450454
TI  - Cow's milk allergenicity.
AB  - In this review, clinical and epidemiological aspects of milk allergy along with
      current data on the structure and function of the main cow's milk allergens, are
      presented. Milk allergy is the most frequent food allergy in childhood. One of
      the reasons why allergy to cow's milk shows its highest prevalence in children is
      its early introduction into the diets of infants when breast feeding is not
      possible. The major allergens are caseins, a-lactalbumin and beta-lactoglobulin,
      but allergies to other minor proteins (immunoglobulins, bovine serum albumin)
      have also been reported. Milk allergenicity can be reduced by various processing
      methods (mainly hydrolysis), and processed formulas based on cow's milk can often
      be safely introduced to children allergic to milk proteins. Cross reactivity has
      been described between different mammalian milks and between milk and meat or
      animal dander. 

PMID- 24450455
TI  - Anti-inflammatory and anti-allergic properties of donkey's and goat's milk.
AB  - Nowadays, donkey's and goat's milk consumption has been reevaluated for its
      potential benefits to human health. For example, in infants with intolerance to
      cow's milk, donkey's milk represents a good alternative due to its chemical
      characteristics similar to those of human milk. On the other hand, goat's milk in
      virtue of its higher content in short chain, medium chain, mono and
      polyunsaturated fatty acids than that of cow's milk, is more digestible than the
      bovine counterpart. From an immunological point of view, donkey's milk is able to
      induce release of inflammatory and anti-inflammatory cytokines from normal human
      peripheral blood lymphomononuclear cells, thus maintaining a condition of immune
      homeostasis. Similarly, goat's milk has been shown to trigger innate and adaptive
      immune responses in an in vitro human system, also inhibiting the endotoxin
      induced activation of monocytes. Finally, in these milks the presence of their
      own microbiota may normalize the human intestinal microbiota with a cascade of
      protective effects at intestinal mucosal sites, even including triggering of
      intestinal T regulatory cells. In the light of the above considerations, donkey's
      and goat's milk should be recommended as a dietary supplement in individuals with
      inflammatory and allergic conditions, even including elderly people. 

PMID- 24450456
TI  - Cow's milk allergy: where have we come from and where are we going?
AB  - Since the 1930's the scientific literature on cow's milk protein allergy (CMPA)
      has accumulated. Over the last decade new diagnostic tools and treatment
      approaches have been developed. The diagnosis of reproducible adverse reactions
      to cow's milk proteins (CMP), i.e. CMPA, still has to be confirmed by controlled
      elimination and challenge procedures. Advanced diagnostic testing using epitope
      and microarray technology may in the future improve the diagnostic accuracy of
      CMPA by determination of specific IgE against specific allergen components of
      cow's milk protein. The incidence of CMPA in early childhood is approximately 2
      3% in developed countries. Symptoms suggestive of CMPA may be encountered in 5
      15% of infants emphasizing the importance of controlled elimination/milk
      challenge procedures. Reproducible clinical reactions to CMP in human milk have
      been reported in 0.5% of breastfed infants. Most infants with CMPA develop
      symptoms before 1 month of age, often within 1 week after inter introduction of
      CMP-based formula. The majority has two or more symptoms from two or more organ
      systems. Approximately 50-70% have cutaneous symptoms, 50-60% gastrointestinal
      symptoms and 20-30% respiratory symptoms. Symptoms may occur within 1 hour after
      milk intake (immediate reactions) or after 1 hour (late reactions). The prognosis
      of CMPA is good with a remission rate of approximately 45 to 50% at 1 year, 60 to
      75% at 2 years and 85 to 90% at 3 years. Associated adverse reactions to other
      foods develop in up to 50% and allergy against inhalants in 50 to 80%. The basic
      treatment of CMPA is avoidance of CMP. In early childhood a milk substitute is
      needed. Documented extensively hydrolysed formulas are recommended, whereas
      partially hydrolysed formulas should not be used because of a high degree of
      antigenicity and allergenicity associated with adverse reactions. In case of
      intolerance to extensively hydrolysed formulas and multiple food allergies a
      formula based on aminoacids is recommended. Alternative milk substitutes such as
      sheep's and goat's milk should not be used because of a high degree of cross
      reactivity with CMP. Milk from other mammals such as mare and donkey may be
      tolerated by some children with CMPA. Soy protein is as allergenic as CMP and soy
      formula is not recommended for young children with CMPA because of a great risk
      of development of allergy to soy, whereas soymilk is normally tolerated in older
      children with CMPA. Recent treatment modalities are oral immunotherapy (OIT)
      involving the ingestion of increasing amounts of milk allergen on a regular basis
      to desensitize and potentially permanently tolerize patients to CMP. OIT can
      increase the reaction thresholds to CMP, but questions about safety and long-term
      efficacy remain. Anti-IgE therapy with Omalizumab may improve the safety and
      efficacy of OIT and may provide benefit in monotherapy. 

PMID- 24450457
TI  - Cow's milk allergy: where do we stand?

PMID- 24450458
TI  - Monofunctional hyperbranched ethylene oligomers.
AB  - The neutral kappa(2)N,O-salicylaldiminato Ni(II) complexes [kappa(2)N,O-{(2,6
      (3',5'-R2C6H3)2C6H3-N?C(H)-(3,5-I2-2-O-C6H2)}]NiCH3(pyridine)] (1a-pyr, R = Me;
      1b-pyr, R = Et; 1c-pyr, R = iPr) convert ethylene to hyperbranched low-molecular
      weight oligomers (Mn ca. 1000 g mol(-1)) with high productivities. While all
      three catalysts are capable of generating hyperbranched structures, branching
      densities decrease significantly with the nature of the remote substituent along
      Me > Et > iPr and oligomer molecular weights increase. Consequently, only 1a-pyr
      forms hyperbranched structures over a wide range of reaction conditions (ethylene
      pressure 5-30 atm and 20-70  degrees C). An in situ catalyst system achieves
      similar activities and identical highly branched oligomer microstructures,
      eliminating the bottleneck given by the preparation and isolation of Ni-Me
      catalyst precursor species. Selective introduction of one primary carboxylic acid
      ester functional group per highly branched oligoethylene molecule was achieved by
      isomerizing ethoxycarbonylation and alternatively cross metathesis with ethyl
      acrylate followed by hydrogenation. The latter approach results in complete
      functionalization and no essential loss of branched oligomer material and
      molecular weight, as the reacting double bonds are close to a chain end.
      Reduction yielded a monoalcohol-functionalized oligomer. Introduction of one
      reactive epoxide group per branched oligomer occurs completely and selectively
      under mild conditions. All reaction steps involved in oligomerization and
      monofunctionalization are efficient and readily scalable. 

PMID- 24450460
TI  - Effectiveness and durability of the rice pi-ta gene in Yunnan province of China.
AB  - Rice blast is one of the most damaging diseases of rice worldwide. In the present
      study, we analyzed DNA sequence variation of avirulence (AVR) genes of AVR-Pita1
      in field isolates of Magnaporthe oryzae in order to understand the effectiveness
      of the resistance gene Pi-ta in China. Genomic DNA of 366 isolates of M. oryzae
      collected from Yunnan province of China were used for polymerase chain reaction
      (PCR) amplification to examine the existence of AVR-Pita1 using gene-specific PCR
      markers. Results of PCR products revealed that 218 isolates of M. oryzae carry
      AVR-Pita1. Among of them, 62.5, 56.3, 58.5, 46.7, 72.4, and 57.4% of M. oryzae
      carry AVR-Pita1 from northeastern, southeast, western, northwest, southwestern,
      and central Yunnan province, respectively. The detection rate of AVR-Pita1 was,
      in order: southwestern > northeastern > western > central > southeastern >
      northwestern Yunnan province. Moreover, in total, 18 AVR-Pita1 haplotypes
      encoding 13 novel AVR-Pita1 variants were identified among 60 isolates. Most DNA
      sequence variation was found to occur in the exon region, resulting in amino acid
      substitution. Six virulent haplotypes of AVR-Pita1 to Pita were identified among
      60 field isolates. The AVR-Pita1 has evolved to virulence from avirulent origins
      via base substitution. These findings demonstrate that AVR-Pita1 is under
      positive selection and mutations of AVR-Pita1 are responsible for defeating race
      specific resistance in nature.

PMID- 24450459
TI  - Site-specific DNA-doxorubicin conjugates display enhanced cytotoxicity to breast
      cancer cells.
AB  - Doxorubicin (Dox) is widely used for breast cancer treatment but causes serious
      side effects including cardiotoxicity that may adversely impact patient lifespan
      even if treatment is successful. Herein, we describe selective conjugation of Dox
      to a single site in a DNA hairpin resulting in a highly stable complex that
      enables Dox to be used more effectively. Selective conjugation of Dox to G15 in
      the hairpin loop was verified using site-specific labeling with [2-(15)N]-2'
      deoxyguanosine in conjunction with [(1)H-(15)N] 2D NMR, while 1:1 stoichiometry
      for the conjugate was validated by ESI-QTOF mass spectrometry and UV
      spectroscopy. Molecular modeling indicated covalently bound Dox also intercalated
      into the stem of the hairpin and stability studies demonstrated the resulting Dox
      conjugated hairpin (DCH) complex had a half-life >30 h, considerably longer than
      alternative covalent and noncovalent complexes. Secondary conjugation of DCH with
      folic acid (FA) resulted in increased internalization into breast cancer cells.
      The dual conjugate, DCH-FA, can be used for safer and more effective chemotherapy
      with Dox and this conjugation strategy can be expanded to include additional
      anticancer drugs. 

PMID- 24450461
TI  - What interval characteristics make a good categorical disease assessment scale?
AB  - Plant pathologists most often obtain quantitative information on disease severity
      using visual assessments. Category scales have been used for assessing plant
      disease severity in field experiments, epidemiological studies, and for screening
      germplasm. The most widely used category scale is the Horsfall-Barratt (H-B)
      scale, but reports show that estimates of disease severity using the H-B scale
      are less precise compared with nearest percent estimates (NPEs) using the 0 to
      100% ratio scale. Few studies have compared different category scales. The
      objective of this study was to compare NPEs, the H-B midpoint converted data, and
      four different linear category scales (5 and 10% increments, with and without
      additional grades at low severity [0.1, 0.5, 1.0, 2.0, 5.0, 10.0, 15.0,
      20.0...100%, and 0.1, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, 30.0...100%,
      respectively]). Results of simulations based on known distributions of disease
      estimation using the type II error rate (the risk of failing to reject H0 when H0
      is false) showed that at disease severity <= 5%, a 10% category scale had a
      greater probability of failing to reject H0 when H0 is false compared with all
      other methods, while the H-B scale performed least well at 20 to 50% severity.
      The 5% category scale performed as well as NPEs except when disease severity was
      <= 1%. Both the 5 and 10% category scales with the additional grades included
      performed as well as NPEs. These results were confirmed with a mixed model
      analysis and bootstrap analysis of the original rater assessment data. A better
      knowledge of the advantages and disadvantages of category scale types will
      provide a basis for plant pathologists and plant breeders seeking to maximize
      accuracy and reliability of assessments to make an informed decision when
      choosing a disease assessment method.

PMID- 24450462
TI  - Predicting Fusarium head blight epidemics with boosted regression trees.
AB  - Predicting major Fusarium head blight (FHB) epidemics allows for the judicious
      use of fungicides in suppressing disease development. Our objectives were to
      investigate the utility of boosted regression trees (BRTs) for predictive
      modeling of FHB epidemics in the United States, and to compare the predictive
      performances of the BRT models with those of logistic regression models we had
      developed previously. The data included 527 FHB observations from 15 states over
      26 years. BRTs were fit to a training data set of 369 FHB observations, in which
      FHB epidemics were classified as either major (severity >= 10%) or non-major
      (severity < 10%), linked to a predictor matrix consisting of 350 weather-based
      variables and categorical variables for wheat type (spring or winter), presence
      or absence of corn residue, and cultivar resistance. Predictive performance was
      estimated on a test (holdout) data set consisting of the remaining 158
      observations. BRTs had a misclassification rate of 0.23 on the test data, which
      was 31% lower than the average misclassification rate over 15 logistic regression
      models we had presented earlier. The strongest predictors were generally one of
      mean daily relative humidity, mean daily temperature, and the number of hours in
      which the temperature was between 9 and 30 degrees C and relative humidity >= 90%
      simultaneously. Moreover, the predicted risk of major epidemics increased
      substantially when mean daily relative humidity rose above 70%, which is a lower
      threshold than previously modeled for most plant pathosystems. BRTs led to novel
      insights into the weather-epidemic relationship.

PMID- 24450463
TI  - Newborn mouse lens proteome and its alteration by lysine 6 mutant ubiquitin.
AB  - Ubiquitin is a tag that often initiates degradation of proteins by the proteasome
      in the ubiquitin proteasome system. Targeted expression of K6W mutant ubiquitin
      (K6W-Ub) in the lens results in defects in lens development and cataract
      formation, suggesting critical functions for ubiquitin in lens. To study the
      developmental processes that require intact ubiquitin, we executed the most
      extensive characterization of the lens proteome to date. We quantified lens
      protein expression changes in multiple replicate pools of P1 wild-type and K6W-Ub
      expressing mouse lenses. Lens proteins were digested with trypsin, peptides were
      separated using strong cation exchange and reversed-phase liquid chromatography,
      and tandem mass (MS/MS) spectra were collected with a linear ion trap. Transgenic
      mice that expressed low levels of K6W-Ub (low expressers) had normal, clear
      lenses at birth, whereas the lenses that expressed high levels of K6W-Ub (higher
      expressers) had abnormal lenses and cataracts at birth. A total of 2052 proteins
      were identified, of which 996 were reliably quantified and compared between wild
      type and K6W-Ub transgenic mice. Consistent with a delayed developmental program,
      fiber-cell-specific proteins, such as gamma-crystallins (gammaA, gammaB, gammaC,
      and gammaE), were down-regulated in K6W-Ub higher expressers. Up-regulated
      proteins were involved in energy metabolism, signal transduction, and
      proteolysis. The K6W-Ub low expressers exhibited delayed onset and milder
      cataract consistent with smaller changes in protein expression. Because lens
      protein expression changes occurred prior to lens morphological abnormalities and
      cataract formation in K6W-Ub low expressers, it appears that expression of K6W-Ub
      sets in motion a process of altered protein expression that results in
      developmental defects and cataract. 

PMID- 24450468
TI  - Electron inelastic mean free path theory and density functional theory resolving
      discrepancies for low-energy electrons in copper.
AB  - We develop the many-pole dielectric theory of UV plasmon interactions and
      electron energy losses, and couple our advances with recent developments of Kohn
      Sham density functional theory to address observed discrepancies between high
      precision measurements and tabulated data for electron inelastic mean free paths
      (IMFPs). Recent publications have demonstrated that a five standard error
      difference exists between longstanding theoretical calculations and measurements
      of electron IMFPs for elemental solids at energies below 120 eV, a critical
      region for analysis of electron energy loss spectroscopy (EELS), X-ray absorption
      spectroscopy (XAS), and related technologies. Our implementation of improved
      optical loss spectra and a physical treatment of second-order excitation
      lifetimes resolves this problem in copper for the first time for energies in
      excess of 80 eV and substantially improves agreement for lower energy electrons. 

PMID- 24450470
TI  - The role of anxiety, depression, and psychological stress on the clinical status
      of recurrent aphthous stomatitis and oral lichen planus.
AB  - BACKGROUND: In spite of all the efforts, recurrent aphthous stomatitis (RAS) and
      oral lichen planus (OLP) still have unexplained etiology. The role of anxiety,
      depression, and psychological stress in occurrence and intensity of symptoms in
      RAS and OLP patients has been investigated in this study. METHODS: A total of 110
      patients with RAS in the acute phase and 112 patients with OLP also in acute
      phase participated in this study. All patients filled out questionnaires related
      to the primary disease (RAS/OLP) after which they took the following
      psychological tests: Beck Depression Inventory (BDI), The State-Trait Anxiety
      Inventory (STAI), and Ways of Coping Questionnaire (WCQ). RESULTS: According to
      multiple regression analysis, in patients with RAS, the highest correlation was
      found between results of the pain intensity and STAI test (beta= 0.66; p <
      0.000). In the patients with OLP, the highest correlation was found between the
      level of hyperkeratosis and WCQ test (beta = 0.53; P < 0.000), inflammation and
      results of BDI test (beta = 0.33; P < 0.002), and results of dynia test and STAI
      test (beta = 0.31; P < 0.004). CONCLUSIONS: In this study, a high correlation
      between anxiety, depression, and psychological stress with symptoms of RAS and
      OLP has been observed.

PMID- 24450471
TI  - A randomized controlled trial to evaluate the effect of incorporating peanuts
      into an American Diabetes Association meal plan on the nutrient profile of the
      total diet and cardiometabolic parameters of adults with type 2 diabetes.
AB  - BACKGROUND: According to the American Diabetes Association (ADA), the nutritional
      goals for patients with type 2 diabetes (T2D) are to achieve an optimal nutrient
      intake to achieve normoglycemia and a cardioprotective lipid profile. Peanuts are
      nutrient dense foods that contain high levels of monounsaturated fat (MUFA) and
      are a natural source of arginine, fiber, phytosterols, resveritrol, niacin,
      folate, vitamin E and magnesium, which have the potential for improving blood
      lipids and glycemic control. This study sought to evaluate the effect of a peanut
      enriched ADA meal plan on the nutrient profile of the total diet and
      cardiometabolic parameters in adults with T2D. METHODS: This was a randomized,
      prospective 24-week parallel-group clinical trial with 60 adults with T2D [age
      range 34-84 years; body mass index (BMI) range 17.2-48.7 kg/m2]. Subjects
      consumed an ADA meal plan containing ~20% of energy from peanuts (peanut group)
      or a peanut-free ADA meal plan (control group). Weight, BMI, waist circumference
      (WC) and nutrient intake from 24-hour recalls were measured every 4 weeks and
      fasting blood glucose (FBG), HbA1c and blood lipids were measured every 12 weeks.
      A mixed-model repeated-measures analysis of covariance was performed to assess
      the significance of changes in the cardiometabolic parameters. RESULTS: A higher
      polyunsaturated fat (PUFA) to saturated fat diet ratio and higher intake of MUFA,
      PUFA, alpha-tocopherol, niacin and magnesium was observed in the peanut group as
      compared to the control group (P < 0.01-P = 0.04). Both groups experienced mild
      reductions in weight, BMI, and WC during the study (P = 0.01-P = 0.03), however
      there were no differences between the two groups in these measurements or in FBG,
      HbA1c or blood lipids. For each kilogram of weight loss in the entire cohort
      there were associations for reductions in WC of 0.48 cm (P < 0.01), FBG of 0.11
      mmol/l (P = 0.01) and HbA1c of 0.07% (P < 0.01). CONCLUSIONS: Daily consumption
      of a peanut enriched (46 g/d) ADA meal plan over 24 weeks improves the nutrient
      profile of the total diet and is compatible with weight management and
      improvement in specific blood lipids. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00937222.

PMID- 24450472
TI  - Degenerative myelopathy in a SOD1 compound heterozygous Bernese mountain dog.

PMID- 24450467
TI  - COPD management according to old and new GOLD guidelines: an observational study
      with Italian general practitioners.
AB  - BACKGROUND: Guideline recommendations for COPD management are only partially
      applied within primary care clinical practice. OBJECTIVE: To compare the COPD
      management by Italian general practitioners (GPs) according to either the old
      GOLD (oGOLD) or the new GOLD (nGOLD) guidelines. RESEARCH DESIGN AND METHODS:
      Observational study in different Italian areas. A total of 176 GPs enrolled their
      patients with a COPD diagnosis. Questionnaires were used to collect data on: COPD
      symptoms, disease severity, exacerbations, prescribed pharmacological and non
      pharmacological treatments. COPD severity was estimated according to oGOLD and
      nGOLD guidelines. RESULTS: A total of 526 subjects had complete information to
      assess COPD severity level according to guidelines (symptoms level, spirometry,
      history of exacerbations). The investigated subjects were more frequently males
      (71.2%) with a mean age of 72.5 years, and ex-smokers (44.4%). GPs reported
      sufficient control of the disease in 47.2% of the subjects with over two
      exacerbations in the last 12 months. Most patients have moderate COPD (51.5%),
      according to oGOLD, and belong to D groups (high risk, more symptoms) (45.6%),
      according to nGOLD. Overall, a low use of post-bronchodilator spirometry (65.1%)
      and of pulmonary rehabilitation (13.4%) was shown. The results highlighted a low
      prescriptive appropriateness but with higher value according to nGOLD than oGOLD:
      61.4% vs 35.6%. STUDY LIMITATIONS: Prescription data only provide limited
      information to judge prescribing quality, thus the results have to be evaluated
      with caution; moreover, this study was not designed to assess the difference
      between oGOLD and nGOLD. CONCLUSIONS: Guideline recommendations are applied only
      partially within clinical practice. A higher prescriptive appropriateness is
      shown by GPs using nGOLD classification. This might be due to the fact that
      nGOLD, with respect to oGOLD, takes into account anamnestic usual features
      considered by GPs in their clinical practice.

PMID- 24450473
TI  - Variability in uptake efficiency for pulsed versus constant concentration
      delivery of inhaled nitric oxide.
AB  - BACKGROUND: Nitric oxide (NO) is currently administered using devices that
      maintain constant inspired NO concentrations. Alternatively, devices that deliver
      a pulse of NO during the early phase of inspiration may have use in optimizing NO
      dosing efficiency and in extending application of NO to long-term use by
      ambulatory, spontaneously breathing patients. The extent to which the amount of
      NO delivered for a given pulse sequence determines alveolar concentrations and
      uptake, and the extent to which this relationship varies with breathing pattern,
      physiological, and pathophysiological parameters, warrants investigation.
      METHODS: A mathematical model was used to analyze inhaled nitric oxide (NO)
      transport through the conducting airways, and to predict uptake from the alveolar
      region of the lung. Pulsed delivery was compared with delivery of a constant
      concentration of NO in the inhaled gas. RESULTS: Pulsed delivery was predicted to
      offer significant improvement in uptake efficiency compared with constant
      concentration delivery. Uptake from the alveolar region depended on pulse timing,
      tidal volume, respiratory rate, lung and dead space volume, and the diffusing
      capacity of the lung for NO (DLNO). It was predicted that variation in uptake
      efficiency with breathing pattern can be limited using a pulse time of less than
      100 ms, with a delay of less than 50 ms between the onset of inhalation and pulse
      delivery. Nonlinear variation in uptake efficiency with DLNO was predicted, with
      uptake efficiency falling off sharply as DLNO decreased below ~50-60 ml/min/mm
      Hg. Gas mixing in the conducting airways played an important role in determining
      uptake, such that consideration of bulk convection alone would lead to errors in
      assessing efficiency of pulsed delivery systems. CONCLUSIONS: Pulsed NO delivery
      improves uptake efficiency compared with constant concentration delivery.
      Optimization of pulse timing is critical in limiting intra- and inter-subject
      variability in dosing.

PMID- 24450474
TI  - Sources of work-related acute fatigue in United States hospital nurses.
AB  - This study identified the nursing work activities that could be the primary
      sources of work-related acute fatigue in US hospital nurses. Continuous recording
      of working heart rate and random observations of nursing activities were applied
      to collect data from eight nurses during two consecutive 12 h day shifts. Using
      descriptive statistics and random-effect analysis of variance, the contributions
      of individual nursing work activities to acute fatigue were compared based on the
      activity frequencies and nurses' corresponding heart rate elevations. Of 860
      observed nursing-related work activities, manual patient-handling, bedside-care,
      care-coordinating, and walking/standing activities accounted for 5%, 16%, 38%,
      and 41%, respectively. After controlling for the differences of participant and
      shift, the percentage of working heart rate to maximal heart rate of manual
      patient-handling (64.3%), bedside-care (59.7%), and walking/standing (57.4%)
      activities were significantly higher than that of care-coordinating activities
      (52.3%, F[3, 38.0]  = 7.5, P < 0.001). These findings suggest that bedside care
      and walking/standing, other than manual patient handling, contributed most to the
      level of acute fatigue.

PMID- 24450476
TI  - Patient expectations and experiences in idiopathic pulmonary fibrosis:
      implications of patient surveys for improved care.
AB  - For patients with idiopathic pulmonary fibrosis (IPF), prognosis is extremely
      poor and treatment options are limited. An improved understanding of the
      experiences and expectations of IPF patients could lead to better clinical
      management and patient satisfaction. A review of the literature found that
      diagnosis of IPF typically involved a protracted course including multiple
      evaluations. Patients felt that educational resources were inadequate and
      inaccessible. Overall, patients had reasonable expectations for IPF-specific
      therapies, and were enthusiastic about trying promising new therapies. Numerous
      domains of health and functioning identified by patients as important were
      impaired because of IPF. Existing patient-reported outcome instruments (including
      assessments of health-related quality of life) do not capture many of these
      domains or are irrelevant to patients with IPF, highlighting the need for an IPF
      specific instrument. Patients treated in centers of excellence expressed greater
      satisfaction with quality of care and treatments, and also valued the opportunity
      to interact with other IPF patients. 

PMID- 24450475
TI  - CD34+ VEGFR-3+ progenitor cells have a potential to differentiate towards
      lymphatic endothelial cells.
AB  - Endothelial progenitor cells (EPCs) play an important role in postnatal
      neovascularization. However, it is poorly understood whether EPCs contribute to
      lymphangiogenesis. Here, we assessed differentiation of a novel population of
      EPCs towards lymphatic endothelial cells and their lymphatic formation. CD34(+)
      VEGFR-3(+) EPCs were isolated from mononuclear cells of human cord blood by
      fluorescence-activated cell sorting. These cells expressed CD133 and displayed
      the phenotype of the endothelial cells. Cell colonies appeared at 7-10 days after
      incubation. The cells of the colonies grew rapidly and could be repeatedly
      subcultured. After induction with VEGF-C for 2 weeks, CD34(+) VEGFR-3(+) EPCs
      could differentiate into lymphatic endothelial cells expressing specific markers
      5'-nucleotidase, LYVE-1 and Prox-1. The cells also expressed hyaluronan receptor
      CD44. The differentiated cells had properties of proliferation, migration and
      formation of lymphatic capillary-like structures in three-dimensional collagen
      gel and Matrigel. VEGF-C enhanced VEGFR-3 mRNA expression. After interfering with
      VEGFR-3 siRNA, the effects of VEGF-C were diminished. These results demonstrate
      that there is a population of CD34(+) VEGFR-3(+) EPCs with lymphatic potential in
      human cord blood. VEGF-C/VEGFR-3 signalling pathway mediates differentiation of
      CD34(+) VEGFR-3(+) EPCs towards lymphatic endothelial cells and
      lymphangiogenesis. Cord blood-derived CD34(+) VEGFR-3(+) EPCs may be a reliable
      source in transplantation therapy for lymphatic regenerative diseases.

PMID- 24450477
TI  - Bringing breast reconstruction to the forefront.

PMID- 24450478
TI  - Proteoglycans maintain lung stability in an elastase-treated mouse model of
      emphysema.
AB  - Extracellular matrix remodeling and tissue rupture contribute to the progression
      of emphysema. Lung tissue elasticity is governed by the tensile stiffness of
      fibers and the compressive stiffness of proteoglycans. It is not known how
      proteoglycan remodeling affects tissue stability and destruction in emphysema.
      The objective of this study was to characterize the role of remodeled
      proteoglycans in alveolar stability and tissue destruction in emphysema. At 30
      days after treatment with porcine pancreatic elastase, mouse lung tissue
      stiffness and alveolar deformation were evaluated under varying tonicity
      conditions that affect the stiffness of proteoglycans. Proteoglycans were stained
      and measured in the alveolar walls. Computational models of alveolar stability
      and rupture incorporating the mechanical properties of fibers and proteoglycans
      were developed. Although absolute tissue stiffness was only 24% of normal,
      changes in relative stiffness and alveolar shape distortion due to changes in
      tonicity were increased in emphysema (P < 0.01 and P < 0.001). Glycosaminoglycan
      amount per unit alveolar wall length, which is responsible for proteoglycan
      stiffness, was higher in emphysema (P < 0.001). Versican expression increased in
      the tissue, but decorin decreased. Our network model predicted that the rate of
      tissue deterioration locally governed by mechanical forces was reduced when
      proteoglycan stiffness was increased. Consequently, this general network model
      explains why increasing proteoglycan deposition protects the alveolar walls from
      rupture in emphysema. Our results suggest that the loss of proteoglycans observed
      in human emphysema contributes to disease progression, whereas treatments that
      promote proteoglycan deposition in the extracellular matrix should slow the
      progression of emphysema. 

PMID- 24450479
TI  - Assembly and stoichiometry of FliF and FlhA in Salmonella flagellar basal body.
AB  - The bacterial flagellar export apparatus is required for the construction of the
      bacterial flagella beyond the cytoplasmic membrane. The membrane-embedded part of
      the export apparatus, which consists of FlhA, FlhB, FliO, FliP, FliQ and FliR, is
      located in the central pore of the MS ring formed by 26 copies of FliF. The C
      terminal cytoplasmic domain of FlhA is located in the centre of the cavity within
      the C ring made of FliG, FliM and FliN. FlhA interacts with FliF, but its
      assembly mechanism remains unclear. Here, we fused yellow fluorescent protein
      (YFP) and cyan fluorescent protein (CFP) to the C-termini of FliF and FlhA and
      investigated their subcellular localization by fluorescence microscopy. The
      punctate pattern of FliF-YFP localization required FliG but neither FliM, FliN,
      FlhA, FlhB, FliO, FliP, FliQ nor FliR. In contrast, FlhA-CFP localization
      required FliF, FliG, FliO, FliP, FliQ and FliR. The number of FlhA-YFP molecules
      associated with the MS ring was estimated to be about nine. We suggest that FlhA
      assembles into the export gate along with other membrane components during the MS
      ring complex formation in a co-ordinated manner. 

PMID- 24450481
TI  - Stratification of paracetamol overdose patients using new toxicity biomarkers:
      current candidates and future challenges.
AB  - One of the most common causes of acute liver failure in the Western world is
      paracetamol (acetaminophen) overdose. Specific and sensitive detection of liver
      injury is important for the prompt and safe treatment of patients with the
      antidote N-acetylcysteine (NAC) and for the determination of NAC efficacy.
      Despite many years of intense research, the precise mechanisms of paracetamol
      induced liver injury in humans are still not defined, and few studies have
      examined the optimal dosing regimen for clinical NAC use. It has been widely
      acknowledged that circulating biomarkers such as microRNA-122, keratin-18 and
      high mobility group box-1 hold potential to inform on the mechanistic-basis of
      human drug-induced liver injury. Here, we provide a perspective on the
      application of these mechanistic biomarkers to the deeper understanding of
      paracetamol hepatotoxicity in clinical and preclinical studies. Also, we discuss
      current barriers to using these experimental biomarkers to stratify patients
      presenting to hospital with this common medical emergency. 

PMID- 24450480
TI  - Increased IL-4 mRNA expression and poly-aromatic hydrocarbon concentrations from
      children with asthma.
AB  - BACKGROUND: Asthma is the most common chronic childhood disease. Imbalance of
      cytokines released from T helper cells and environmental factors, such as
      exposure to poly-aromatic hydrocarbon (PAH), play pivotal roles in the
      pathogenesis of asthma. The aim of this study was to compare the mRNA expression
      patterns of Interleukin (IL)-4, interferon (IFN)-gamma and Acyl Co A long chain 3
      (ACSL3) in peripheral blood leukocytes of children with and without asthma. To
      correlate the obtained mRNA data with serum IL-4, IFN-gamma and PAH levels.
      Further, to determine the effect of in vivo exposure to PAH on mRNA expression of
      IL-4, IFN-gamma and ACSL3 genes in a rat model. METHODS: A total of 170 children
      below 16 years (85 pediatric asthma patients and 85 matched healthy controls)
      were randomly selected from the Riyadh Cohort, Saudi Arabia. Gene expression
      analysis was performed using qRTPCR. Serum IL-4, IFN-gamma and PAH were measured
      using LINCOplex (human multiplex immunoassay kit) and HPLC respectively. RESULTS:
      IL-4 mRNA expression was significantly increased (P < 0.05) in children with
      asthma compared to healthy control group whereas no differences were observed for
      either IFN-gamma or ACSL3 mRNA. Similarly, serum IL- 4 and PAHs concentration was
      significantly higher as well in children with asthma in whom IFN-gamma was also
      significantly lower. Results obtained in rats showed that exposure to the
      benzopyrene prototype PAH resulted in a 2.6 fold (P < 0.001) increased IL-4 mRNA
      expression in blood. CONCLUSION: Peripheral blood IL-4 mRNA levels, serum
      concentration of this cytokine are elevated in children with asthma. Also,
      elevated levels of PAH were observed in children with asthma. Additionally, PAH
      administration in rodents resulted in an increased IL-4 mRNA which is supposed to
      partly mediate the inflammatory response noted in asthma.

PMID- 24450482
TI  - Primary ciliary dyskinesia: critical evaluation of clinical symptoms and
      diagnosis in patients with normal and abnormal ultrastructure.
AB  - BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare disorder with variable
      disease progression. To date, mutations in more than 20 different genes have been
      found. At present, PCD subtypes are described according to the ultrastructural
      defect on transmission electron microscopy (TEM) of the motile cilia. PCD with
      normal ultrastructure (NU) is rarely reported because it requires additional
      testing. Biallelic mutations in DNAH11 have been described as one cause of PCD
      with NU.The aim of our study was to describe the clinical characteristics of a
      large population of patients with PCD, in relation to the ultrastructural defect.
      Additionally, we aimed to demonstrate the need for biopsy and cell culture to
      reliably diagnose PCD, especially the NU subtype. METHODS: We retrospectively
      analyzed data from 206 patients with PCD. We compared the clinical
      characteristics, lung function, microbiology and imaging results of 68 patients
      with PCD and NU to those of 90 patients with dynein deficiencies and 41 patients
      with central pair abnormalities. In addition, we aimed to demonstrate the
      robustness of the diagnosis of the NU subtype in cell culture by data from
      genetic analysis. RESULTS: PCD with NU comprised 33% (68/206) of all patients
      with PCD. Compared to other subtypes, patients with PCD and NU had a similar
      frequency of upper and lower respiratory tract problems, as well as similar lung
      function and imaging. With the currently widely applied approach, without cell
      culture, the diagnosis would have been missed in 16% (11/68) of patients with NU.
      Genetic analysis was performed in 29/68 patients with PCD and NU, and biallelic
      mutations were found in 79% (23/29) of tested patients. CONCLUSIONS: We reported
      on the clinical characteristics of a large population of patients with PCD and
      NU. We have shown that systematic performance of biopsy and cell culture
      increases sensitivity to detect PCD, especially the subtype with NU.PCD with NU
      has similar clinical characteristics as other PCD types and requires biopsy plus
      ciliogenesis in culture for optimal diagnostic yield.

PMID- 24450484
TI  - Mechanistic insights into the role of alkylamine in the synthesis of CdSe
      nanocrystals.
AB  - This paper reports a detailed mechanistic study of the effect of alkylamine on
      the synthesis of CdSe nanocrystals. Alkylamines are one of the most important
      additives for the synthesis of colloidal semiconductor nanocrystals. However,
      their effect on the monomer production as well as nanocrystal nucleation and
      growth are not well understood, as indicted by inconsistent and contradictory
      conclusions in the literature. We found that alkylamines slow down the reaction
      between cadmium oleate and trialkyl phosphine selenide by binding to cadmium and
      preventing the activation of trialkyl phosphine selenide. A linear correlation
      was observed between the observed reaction rate constant and the (31)P NMR
      chemical shift or (1)J(P-Se) of phosphine selenide. In the presence of
      alkylamine, an alkylaminophosphonium intermediate was observed. Mechanistic study
      suggests that the cleavage of P?Se bond is through nucleophilic attack by
      carboxylate instead of alkylamine. Interestingly, although alkylamines decrease
      the rate of monomer production, it increases the rate of CdSe nanocrystal growth.
      Although seemingly contradictory, this is due to a drastic decrease in the
      nanocrystal nucleation events in the presence of alkylamines. As a result, each
      nucleus is fed with more monomers and grows faster in the presence of alkylamine
      than in its absence.

PMID- 24450483
TI  - Proteasome inhibitor patents (2010 - present).
AB  - INTRODUCTION: Over the past 3 years, numerous patents and patent applications
      have been submitted and published involving compounds designed to inhibit the
      proteasome. Proteasome inhibition has been of great interest in cancer research
      since disruption of proteolysis leads to a significant buildup of cytotoxic
      proteins and activation of apoptotic pathways, particularly in rapidly
      proliferating cells. The current standards in proteasome inhibition are the only
      FDA-approved inhibitors, bortezomib and carfilzomib. Although these drugs are
      quite effective in treating multiple myeloma and other blood tumors, there are
      shortcomings, including toxicities and resistance. Most of the current patents
      attempt to improve on existing compounds, by increasing bioavailability and
      selectivity, while attempting to reduce toxicity. A general categorization of
      similar compounds was employed to evaluate and compare drug design strategies.
      AREAS COVERED: This review focuses on novel compounds and subsequent analogs
      developed for proteasome inhibition, used in preventing and treating human
      cancers. A comprehensive description and categorization of patents related to
      each type of compound and its derivatives, as well as their uses and efficacies
      as anticancer agents is included. A review of combination therapy patents has
      also been included. EXPERT OPINION: Although there are many diverse chemical
      scaffolds being published, there are few patented proteasome inhibitors whose
      method of inhibition is genuinely novel. Most patents utilize a destructive
      chemical warhead to attack the catalytic threonine residue of the proteasome
      active sites. Few patents try to depart from this, emphasizing the need for
      developing new mechanisms of action and specific targeting.

PMID- 24450485
TI  - Statins and asthma: where we stand, and the next critical steps in research.
AB  - Asthma remains a formidable public health problem with ever increasing annual
      costs and prevalence. There are 300 million people with asthma worldwide. Per the
      Centers for Disease Control and Prevention, there are over 25 million Americans
      with asthma (both children and adults), i.e. one in 12 people have asthma, and
      this is increasing annually. Asthma results in approximately half a million
      hospitalizations and two million emergency department (ED) visits per year. In
      2007 alone, 185 children and 3262 adults died from asthma, i.e. nine to ten
      patients die a day from asthma. This resulted in an annual cost of $56 billion in
      medical costs, lost work/school days, and early deaths. Therefore, we need novel
      and innovative therapies for asthma. In this Editorial, I review results from a
      study by Tse et al. evaluating the therapeutic potential of statins, within the
      context of our current state of knowledge. I review observational studies and
      clinical trials, highlight some potential pitfalls in clinical trial design, and
      discuss important questions for future research.

PMID- 24450486
TI  - A method to incorporate prior information into score test for genetic association
      studies.
AB  - BACKGROUND: The interest of the scientific community in investigating the impact
      of rare variants on complex traits has stimulated the development of novel
      statistical methodologies for association studies. The fact that many of the
      recently proposed methods for association studies suffer from low power to
      identify a genetic association motivates the incorporation of prior knowledge
      into statistical tests. RESULTS: In this article we propose a methodology to
      incorporate prior information into the region-based score test. Within our
      framework prior information is used to partition variants within a region into
      several groups, following which asymptotically independent group statistics are
      constructed and then combined into a global test statistic. Under the null
      hypothesis the distribution of our test statistic has lower degrees of freedom
      compared with those of the region-based score statistic. Theoretical power
      comparison, population genetics simulations and results from analysis of the
      GAW17 sequencing data set suggest that under some scenarios our method may
      perform as well as or outperform the score test and other competing methods.
      CONCLUSIONS: An approach which uses prior information to improve the power of the
      region-based score test is proposed. Theoretical power comparison, population
      genetics simulations and the results of GAW17 data analysis showed that for some
      scenarios power of our method is on the level with or higher than those of the
      score test and other methods.

PMID- 24450487
TI  - Extended cycle combined oral contraceptives and prophylactic frovatriptan during
      the hormone-free interval in women with menstrual-related migraines.
AB  - BACKGROUND: Migraine headaches are a significant problem for American women with
      many of them suffering from headaches around the time of their menstrual cycle.
      Women taking oral contraceptives in the standard 21/7 cycle regimen often suffer
      from headaches around the time of the hormone free intervals (HFIs) as well.
      Extended oral contraceptive regimens have been shown to decrease the frequency,
      but not eliminate these headaches. This study is a double-blind, randomized,
      placebo-controlled pilot study of participants with menstrual-related migraines
      (MRMs) who were initiated on extended combined oral contraceptives and given
      frovatriptan prophylactically during HFIs. METHODS: Participants having
      spontaneous menstrual cycles or taking daily combined oral contraceptives in a
      21/7 regimen with MRMs were placed on a contraceptive containing levonorgestrel
      and ethinyl estradiol. Analyses compared headache scores during pre-study
      baseline cycles to those in a 168-day extended regimen with placebo versus
      frovatriptan treatments during HFIs. RESULTS: Daily headache scores decreased
      (p=0.034) from 1.29 +/- 0.10 during pre-study cycles to 1.10 +/- 0.14 during
      extended combined oral contraceptive use. Frovatriptan blocked the increase in
      headache score over the placebo during HFIs. However, following the withdrawal of
      frovatriptan, headache scores increased (p>0.01) despite resuming combined oral
      contraceptive use. CONCLUSIONS: Extended combined oral contraceptive regimen
      reduces MRM severity. Frovatriptan prevents headaches during HFIs, but is
      associated with new headache symptoms when withdrawn.

PMID- 24450488
TI  - Association between BACH2 expression and clinical prognosis in diffuse large B
      cell lymphoma.
AB  - BACH2, a B cell-specific transcriptional repressor, plays a significant role in B
      cell maturation. Despite a number of previous studies, the clinicopathological
      significance of BACH2 expression in diffuse large B cell lymphoma (DLBCL) remains
      to be established. The present study was performed to validate the significance
      of BACH2 expression as a predictor of prognosis in DLBCL. A total of 94 DLBCL
      cases were included in the present study. All were diagnosed between 2008 and
      2011, and thorough clinical and pathological investigations were possible,
      including immunohistochemical analysis of BACH2. Eighteen cases were selected by
      positive MYC gene alteration (MYC+ group) according to cytogenetic study. The
      remaining 76 cases were subclassified into germinal center B cell phenotype (GCB
      group, 38 cases) or non-GCB phenotype (non-GCB group, 38 cases). There were no
      significant differences between the two groups with regard to clinical
      characteristics and outcomes. In the GCB group, 21 cases were judged to have high
      BACH2 expression, with 19 cases in the non-GCB group. In cases with high BACH2
      expression in GCB and non-GCB groups, the 3-year overall survival (OS) rate was
      significantly shorter than that with low expression (71.7% vs 91.3%, P = 0.0256).
      In the MYC+ group, 15 cases had high BACH2 expression levels. Although overall
      the MYC+ group showed short survival time (3-year OS 35.0%), 3 out of 4 cases
      with low BACH2 expression are alive without disease relapse at the time of
      publication of this paper. In conclusion, BACH2 expression level is a promising
      predictor of prognosis for DLBCL.

PMID- 24450489
TI  - C60@Lysozyme: direct observation by nuclear magnetic resonance of a 1:1 fullerene
      protein adduct.
AB  - Integrating carbon nanoparticles (CNPs) with proteins to form hybrid functional
      assemblies is an innovative research area with great promise for medical,
      nanotechnology, and materials science. The comprehension of CNP-protein
      interactions requires the still-missing identification and characterization of
      the 'binding pocket' for the CNPs. Here, using Lysozyme and C60 as model systems
      and NMR chemical shift perturbation analysis, a protein-CNP binding pocket is
      identified unambiguously in solution and the effect of the binding, at the level
      of the single amino acid, is characterized by a variety of experimental and
      computational approaches. Lysozyme forms a stoichiometric 1:1 adduct with C60
      that is dispersed monomolecularly in water. Lysozyme maintains its tridimensional
      structure upon interaction with C60 and only a few identified residues are
      perturbed. The C60 recognition is highly specific and localized in a well-defined
      pocket. 

PMID- 24450490
TI  - Rebuttal to correspondence on "Changes in droplet surface tension affect the
      observed hygroscopicity of photochemically aged biomass burning aerosol".

PMID- 24450491
TI  - Divergent kinetics differentiate the mechanism of action of two HDAC inhibitors.
AB  - Histone deacetylases (HDACs) play diverse roles in many diseases including
      cancer, sarcopenia, and Alzheimer's. Different isoforms of HDACs appear to play
      disparate roles in the cell and are associated with specific diseases; as such, a
      substantial effort has been made to develop isoform-selective HDAC inhibitors.
      Our group focused on developing HDAC1/HDAC2-specific inhibitors as a cancer
      therapeutic. In the course of characterizing the mechanism of inhibition of a
      novel HDAC1/2-selective inhibitor, it was determined that it did not exhibit
      classical Michaelis-Menten kinetic behavior; this result is in contrast to the
      seminal HDAC inhibitor SAHA. Enzymatic assays, along with a newly developed
      binding assay, were used to determine the rates of binding and the affinities of
      both the HDAC1/2-selective inhibitor and SAHA. The mechanism of action studies
      identified a potential conformational change required for optimal binding by the
      selective inhibitor. A model of this putative conformational change is proposed. 

PMID- 24450492
TI  - Chemopreventive effect of Mentha piperita on dimethylbenz[a]anthracene and
      formaldehyde-induced tongue carcinogenesis in mice (histological and
      immunohistochemical study).
AB  - OBJECTIVE: Cancer chemoprevention is defined as the use of chemicals or dietary
      components to block, inhibit, or reverse the development of cancer in normal or
      pre-neoplastic tissue. Mentha extract (ME) has antioxidant and antiperoxidant
      properties. This study was held to investigate the protective and anticancer
      effect of Mentha leaves aqueous extract on oral epithelium of mice tongues.
      DESIGN: A total of 80 Egyptian albino mice were divided into three groups. Group
      I served as control (not subjected to any kind of treatment), and groups II and
      III were subjected to two-stage chemical carcinogenesis through topical
      application of dimethylbenz[a]anthracene (DMBA) followed by formaldehyde on
      dorsal and ventral surfaces of tongues for 9 weeks. Mentha leaves extract was
      administrated to group III at the same time of cancer induction. Histological
      changes were assessed in H&E sections at 3-week intervals. The anticarcinogenic
      effect of Mentha piperita was tested using immunostain with anticaspase antibody.
      RESULTS: The oral administration of ME reduced the appearance of dysplastic
      cellular changes with 61% and inhibited tumor incidence with 100%. Group I showed
      moderate-to-strong cytoplasmic caspase expression. At 6-week interval, group II
      showed weak-to-moderate caspase expression, while sections from group III showed
      moderate-to-strong caspase expression. High significant statistical difference in
      the total score of caspase 3 expression was found between specimens obtained from
      animals sacrificed at 6 weeks in groups I, II, and III (P = 0.001**). CONCLUSION:
      Our study demonstrated that Mentha piperita has inhibited the initiation and
      promotion of oral dysplastic lesions.

PMID- 24450495
TI  - Adsorption, mobility, and self-association of naphthalene and 1-methylnaphthalene
      at the water-vapor interface.
AB  - The adsorption, mobility, and self-association of naphthalene (NPH) and 1
      methylnaphthalene (1MN), two of the simplest polycyclic aromatic hydrocarbons
      (PAHs), at the surface of liquid water at 289 K were investigated using classical
      molecular dynamics (MD) simulations and free energy profile calculations across
      the water-vapor interface. Both NPH and 1MN, which exhibit a strong preference to
      be adsorbed at the water-vapor interface, are found to readily self-associate at
      the water surface, adopting mostly configurations with distinctly nonparallel
      arrangement of the two monomers. The additional methyl group of 1MN represents
      only a minor perturbation in terms of the hydration properties, interfacial
      orientation, and self-association with respect to NPH. Implications of the
      observed self-association behavior for fluorescence spectroscopy of NPH and 1MN
      in aqueous interfacial environment are discussed. 

PMID- 24450496
TI  - Promoting interprofessional understandings through online learning: a qualitative
      examination.
AB  - Interprofessional education is increasingly a core component of health
      professional curricula. It has been suggested that interprofessional education
      can directly enhance patient care outcomes. However, literature has reported many
      difficulties in its successful implementation. This study investigated students'
      perceptions of participating in an online, Web-based module to facilitate
      interprofessional education. Three focus groups, each with 13-15 students, from
      emergency health (paramedic), nursing, occupational therapy, physiotherapy, and
      nutrition and dietetics were conducted with students who participated in an
      online interprofessional education module at one Australian university. Thematic
      analysis was employed to analyze interview transcripts. Four themes emerged:
      professional understanding, patient-centeredness, comparison with other
      interprofessional education activities, and overcoming geographical boundaries.
      Students were overwhelmingly positive about their learning experiences and the
      value of the module in assisting their understandings of the roles of other
      health professionals. Online approaches to interprofessional education have the
      potential to enhance learning and overcome geographical and logistical issues
      inherent in delivering face-to-face interprofessional education. Furthermore, our
      design approach allowed students to watch how other health professionals worked
      in a way that they were unable to achieve in clinical practice. 

PMID- 24450497
TI  - Improved synthesis and structural reassignment of MC1568: a class IIa selective
      HDAC inhibitor.
AB  - An improved synthesis and structural reassignment of the class IIa selective
      histone deacetylase (HDAC) inhibitor MC1568 are described. 

PMID- 24450498
TI  - Microbial phylogenetic profiling with the Pacific Biosciences sequencing
      platform.
AB  - High-throughput sequencing of 16S rRNA gene amplicons has revolutionized the
      capacity and depth of microbial community profiling. Several sequencing platforms
      are available, but most phylogenetic studies are performed on the 454
      pyrosequencing platform because its longer reads can give finer phylogenetic
      resolution. The Pacific Biosciences (PacBio) sequencing platform is significantly
      less expensive per run, does not rely on amplification for library generation,
      and generates reads that are, on average, four times longer than those from 454
      (C2 chemistry), but the resulting high error rates appear to preclude its use in
      phylogenetic profiling. Recently, however, the PacBio platform was used to
      characterize four electrosynthetic microbiomes to the genus-level for less than
      USD 1,000 through the use of PacBio's circular consensus sequence technology.
      Here, we describe in greater detail: 1) the output from successful 16S rRNA gene
      amplicon profiling with PacBio, 2) how the analysis was contingent upon several
      alterations to standard bioinformatic quality control workflows, and 3) the
      advantages and disadvantages of using the PacBio platform for community
      profiling. 

PMID- 24450499
TI  - Identification of species-specific novel transcripts in pig reproductive tissues
      using RNA-seq.
AB  - Although structural properties of the porcine reproductive system are shared by
      many placental mammals, some combination of these properties is unique to pigs.
      To explore whether genomic elements specific to pigs could potentially underlie
      this uniqueness, we made the first step to identify novel transcripts in two
      representative pig reproductive tissues by the technique of massively parallel
      sequencing. To automate the whole process, we built a computational pipeline,
      which can also be easily extended for similar studies in other species. In total,
      5516 and 9061 novel transcripts were found, and 159 and 252 novel transcripts
      appear to be specific to pigs for the placenta and testis respectively.
      Furthermore, these novel transcripts were found to be enriched in quantitative
      trait loci (QTL) regions for reproduction traits in pigs. We validated eight of
      these novel transcripts by quantitative real-time PCR. With respect to their
      genomic organization and their functional relationship to reproduction, these
      transcripts need to be further validated and explored in various pig breeds to
      better comprehend the relevant aspects of pig physiology that contribute to
      reproductive performance. 

PMID- 24450501
TI  - Protective effects of keratinocyte growth factor-2 on ischemia-reperfusion
      induced lung injury in rats.
AB  - Ischemia-reperfusion (I/R) is a common cause to compromise tissue injury via
      endothelial and epithelial barrier dysfunction and damage. Keratinocyte growth
      factor (KGF)-2 could play an important role in the repair of alveolar epithelial
      damage and maintain the capillary barrier function. The present study aimed to
      investigate the potential effects of KGF-2 on I/R-induced lung injury in rats and
      the related mechanisms. KGF-2 (2.5-10 mg/kg) was administered intratracheally in
      rats 3 days before the left lobe with ischemia for 60 minutes followed by
      reperfusion for 180 minutes. Lung injury was evaluated by measuring lung
      morphology, blood gas analysis, total cell number, and protein concentration in
      the bronchoalveolar lavage fluid. The protective effects of KGF-2 on human
      pulmonary microvascular endothelial cells and related mechanisms were evaluated.
      Pretreatment with KGF-2 significantly prevented I/R-induced lung edema,
      inflammatory cell infiltration, protein exudation, and the release of
      inflammatory cytokines in rats, or I/R-induced endothelial cell apoptosis,
      migration, and barrier dysfunction. Phosphoinositide 3-kinase or epidermal growth
      factor receptor inhibitors attenuated the protective effect of KGF-2 in
      endothelial cells. Our results evidence that the local administration of KGF-2
      may be an alternative to prophylactic or adjunct drug therapies for I/R-induced
      lung injury. 

PMID- 24450500
TI  - Postprandial muscle protein synthesis is higher after a high whey protein,
      leucine-enriched supplement than after a dairy-like product in healthy older
      people: a randomized controlled trial.
AB  - BACKGROUND: Decreased ability of muscles to respond to anabolic stimuli is part
      of the underlying mechanism for muscle loss with aging. Previous studies suggest
      that substantial amounts of essential amino acids (EAA), whey protein and leucine
      are beneficial for stimulation of acute muscle protein synthesis in older adults.
      However, these studies supplied only proteins, and no bolus studies have been
      done with dairy products or supplements that contained also fat and carbohydrates
      besides proteins. The aim of this study was to evaluate whether a specifically
      designed nutritional supplement in older adults stimulates muscle protein
      synthesis acutely to a greater extent than a conventional dairy product.
      Moreover, the combined effect with resistance exercise was studied by using a
      unilateral resistance exercise protocol. METHODS: Utilizing a randomized,
      controlled, double blind study design, healthy older adults received a single
      bolus of a high whey protein, leucine-enriched supplement (EXP: 20 g whey
      protein, 3g total leucine, 150 kcal; n = 9) or an iso-caloric milk protein
      control ( CONTROL: 6g milk protein; n = 10), immediately after unilateral
      resistance exercise. Postprandial mixed muscle protein fractional synthesis rate
      (FSR) was measured over 4h using a tracer infusion protocol with L-[ring-13C6]
      phenylalanine and regular blood and muscle sampling. RESULTS: FSR was
      significantly higher overall after EXP (0.0780 +/- 0.0070%/h) vs CONTROL (0.0574
      +/- 0.0066%/h (EMM +/- SE)) (p = 0.049). No interaction between treatment and
      exercise was observed (p = 0.519). Higher postprandial concentrations of EAA and
      leucine are possible mediating factors for the FSR response, while plasma insulin
      increase did not dictate the FSR response. Moreover, when the protein intake from
      the supplements was expressed per kg leg lean mass (LLM), a significant
      correlation was observed with resting postprandial FSR (r = 0.48, P = 0.038).
      CONCLUSIONS: Ingestion of a high whey protein, leucine-enriched supplement
      resulted in a larger overall postprandial muscle protein synthesis rate in
      healthy older subjects compared with a conventional dairy product. This acute
      effect is promising for long-term effects on parameters of muscle mass, strength
      and function in sarcopenic older people, which requires further study. TRIAL
      REGISTRATION: This trial is registered in the Dutch Trial Register under number
      NTR1823.

PMID- 24450502
TI  - Developing technological solutions for dietary assessment in children and young
      people.

PMID- 24450503
TI  - Liposome bupivacaine for postsurgical pain in an obese woman with chronic pain
      undergoing laparoscopic gastrectomy: a case report.
AB  - INTRODUCTION: To reduce incidence and severity of postsurgical pain and minimize
      the effect of its clinical and economic correlates, multimodal therapy for
      surgical patients is recommended. In this report, we discuss the use of liposome
      bupivacaine, a novel multivesicular formulation of bupivacaine indicated for
      single-dose infiltration into the surgical site to produce postsurgical
      analgesia, as part of a multimodal analgesic regimen in a patient with a history
      of chronic pain scheduled to undergo laparoscopic sleeve gastrectomy. To the best
      of our knowledge, this is the first published report of liposome bupivacaine in
      the setting of laparoscopic sleeve gastrectomy. CASE PRESENTATION: A 35-year-old
      white woman with morbid obesity was admitted for laparoscopic sleeve gastrectomy
      to lose weight prior to hip replacement surgery. Because of a complicated medical
      history that included rheumatoid arthritis, fibromyalgia, diabetes mellitus,
      hypertension, and chronic pain, for which she was receiving high doses of opioid
      analgesics, postsurgical pain management was a concern and she was considered a
      candidate for multimodal analgesia. At initiation of surgery, 50mL of lidocaine
      and epinephrine was infiltrated around the port sites. At the conclusion, 25mL of
      normal sterile saline was added to a 20mL vial of liposome bupivacaine (266mg)
      and injected around the port sites and at the site of liver retraction.
      Laparoscopic sleeve gastrectomy was successfully completed. Our patient was
      discharged to the postanesthesia care unit for approximately four hours before
      discharge to the surgical floor with a pain score of 5 (11-point scale; 0 = no
      pain, 10 = worst possible pain). Her postoperative course was uneventful; no
      adverse events were recorded during surgery or during the remainder of her
      hospital stay. Our patient was discharged on the same opioid regimen used
      previously for control of her preexisting chronic pain. CONCLUSIONS: Liposome
      bupivacaine use in this morbidly obese patient undergoing laparoscopic sleeve
      gastrectomy provided analgesic efficacy and limited postsurgical opioids to a
      level comparable with her baseline opioid regimen for chronic pain. Given her
      complex medical history and previous issues with acute and chronic pain, we
      consider these results highly successful and continue to use liposome bupivacaine
      as part of a multimodal analgesic regimen in an effort to optimize postsurgical
      pain management.

PMID- 24450504
TI  - Clustering of developmental delays in Bavarian preschool children - a repeated
      cross-sectional survey over a period of 12 years.
AB  - BACKGROUND: While most children display a normal development, some children
      experience developmental delays compared to age specific development milestones
      assessed during school entry examination. Data exist on prevalence of delays in
      single areas, but there is lack of knowledge regarding the clustering patterns of
      developmental delays and their determinants. METHODS: During the observation
      period 1997-2008, 12 399 preschool children (5-7 years of age) in one district of
      Bavaria, Germany, were assessed in twelve schooling-relevant development areas.
      The co-occurrence of developmental delays was studied by means of Pearson's
      correlation. Subsequently, a two-step cluster algorithm was applied to identify
      patterns of developmental delays, and multinomial logistic regression was
      conducted to identify variables associated with the specific patterns. RESULTS:
      Fourteen percent of preschool children displayed developmental delays in one and
      19% in two or more of the studied areas. Among those with at least two
      developmental delays, most common was the combination of delays in "fine motor
      skills" + "grapho-motor coordination" (in 9.1% of all children), followed by
      "memory/concentration" + "endurance" (5.8%) and "abstraction" + "visual
      perception" (2.1%). In the cluster analysis, five distinct patterns of delays
      were identified, which displayed different associations with male gender and
      younger age. CONCLUSIONS: While developmental delays can affect single areas,
      clustering of multiple developmental delays is common. Such clustering should be
      taken into account when developing diagnostic tests, in pediatric practice and
      considering interventions to reduce delays.

PMID- 24450506
TI  - The ATTAIN trials: efficacy and safety of telavancin compared with vancomycin for
      the treatment of hospital-acquired and ventilator-associated bacterial pneumonia.
AB  - Hospital-acquired bacterial pneumonia (HABP) is the second most common nosocomial
      infection in the USA and the leading cause of mortality among hospital-acquired
      infections. An increasing proportion of HABP cases are the result of infection
      with methicillin-resistant Staphylococcus aureus (MRSA). Telavancin is a once
      daily injectable, semisynthetic lipoglycopeptide antimicrobial with bactericidal
      activity against susceptible Gram-positive pathogens, including MRSA. The two
      methodologically identical Phase III ATTAIN studies demonstrated that telavancin
      was noninferior to vancomycin for the treatment of HABP, including ventilator
      associated bacterial pneumonia, due to S. aureus (including methicillin-sensitive
      S. aureus and MRSA). Telavancin showed a similar safety profile to vancomycin,
      except that in patients with moderate-to-severe renal impairment, there was
      increased mortality, which warrants caution when using telavancin in this
      population. Now approved in the USA for the treatment of HABP, including
      ventilator-associated bacterial pneumonia, caused by susceptible isolates of S.
      aureus when other alternatives are not suitable, telavancin offers another
      therapeutic option.

PMID- 24450507
TI  - Role of surfactants and salt in aqueous two-phase separation of carbon nanotubes
      toward simple chirality isolation.
AB  - Aqueous two-phase extraction has recently been demonstrated as a new method to
      separate single-wall carbon nanotubes (SWCNTs). In this work, we determined that
      the mechanism of separation is driven by the hydrophobicity of the surfactant, or
      combination of surfactants, at the SWCNT surface. This knowledge allowed us to
      develop a simple approach for obtaining highly enriched single-chirality
      suspensions in only 1 or 2 steps. These results were obtained by strategically
      combining multiple surfactants with different diameter-dependent binding
      affinities for SWCNTs and salts that readjust the surfactant structure within the
      mixed micelle surrounding the SWCNTs. The procedure is successfully applied to
      SWCNTs from different sources (CoMoCAT and HiPco) with various diameter
      distributions (from 0.53 to 1.2 nm). Each separation step is characterized by
      optical absorption, resonant Raman, and photoluminescence excitation
      spectroscopies. By determining the SWCNT sorting mechanism, we were able to
      develop a new set of parameters that separated another chirality. 

PMID- 24450510
TI  - Statin use and clinical outcomes among pneumonia patients.
AB  - It was suggested that statin may improve the outcomes of pneumonia patients.
      However, there are sparse data regarding this topic in ethnic Chinese
      populations. In the present study, we investigated associations between previous
      statin use and pneumonia outcomes in Taiwan with a large-scale matched cohort
      study. A total of 11,576 patients with pneumonia were selected, comprising 2894
      patients with previous statin use and 8682 matched patients. We used a separate
      conditional logistic regression to explore relationships between statin use and
      each clinical outcome, including 'intensive care unit admission,' 'use of
      mechanical ventilation,' 'acute respiratory failure' and 'in-hospital death'. We
      found that patients who were statin users were 0.81 (95% CI 0.74-0.89), 0.80 (95%
      CI 0.71-0.89), 0.84 (95% CI 0.75-0.94) and 0.69 times (95% CI 0.57-0.85) less
      likely to be admitted to the intensive care unit, to have acute respiratory
      failure, to need mechanical ventilation, and to die in the hospital,
      respectively, than patients who were not statin users. In addition, it
      consistently revealed that compared with patients who were not statin users,
      regular statin users had lower ORs of intensive care unit admission, acute
      respiratory failure, the use of mechanical ventilation and in-hospital death.
      However, there were no significant differences in the above adverse outcomes
      between irregular users of statin and non-statin users. We concluded that
      patients with regular previous statin use were significantly associated with
      favourable outcomes during admission for pneumonia in Taiwan.

PMID- 24450512
TI  - The 2013 Annual Autumn Meeting of the British Society of Heart Failure.
AB  - 16th British Society for Heart Failure Annual Autumn Meeting Queen Elizabeth II
      Conference Centre, London, UK, 28-29 November 2013 The 16th Annual Meeting for
      the British Society for Heart Failure took place in the impressive surroundings
      of the Queen Elizabeth II Conference Centre in Westminster (London, UK). Over the
      two-day conference, more than 700 delegates attended - the largest number to
      date. Over 40 talks were delivered by some of the world's experts in heart
      failure. For 2013, the theme was making sense of acute heart failure - a clinical
      entity which is frequently encountered, poorly understood, and for which there
      exists virtually no evidence base for treatment. 

PMID- 24450511
TI  - Oxidative stress in bisphosphonate-related osteonecrosis of the jaws.
AB  - OBJECTIVES: To analyze whether oxidative stress (OS) changes are present in
      patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus
      controls. MATERIALS AND METHODS: Oxidative stress was analyzed in serum and
      unstimulated saliva of three groups: Group 1 consisted of 24 patients who had
      been treated with intravenous bisphosphonates (ivBPs) and developed BRONJ, group
      2 consisted of 20 patients who had received ivBPs and did not develop BRONJ, and
      group 3 comprised 17 control subjects. Reduced glutathione (GSH), malondialdehyde
      (MDA), oxidized glutathione (GSSG), and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo
      dG) levels, as well as the GSSG/GSH ratio, were measured. RESULTS: Mean serum and
      saliva levels of MDA, GSSG, and 8-oxo-dG and the GSSG/GSH ratio were
      significantly higher in patients with BRONJ than in controls. We found no
      significant difference in OS according to BRONJ stage, sex, or location in the
      jaws. Logistic regression analysis revealed that the GSSG/GSH ratio was a
      significant factor predicting the development of BRONJ (P = 0.01). CONCLUSIONS:
      Oxidative stress was detected in patients with BRONJ, and the GSSG/GSH ratio was
      the most significant OS variable found; it was a significant factor predicting
      the development of BRONJ.

PMID- 24450513
TI  - Regulation of the immune response during infectious myocarditis.
AB  - Infectious myocarditis (IM) is a commonly undiagnosed condition that may cause
      several heart diseases, including dilated cardiomyopathy and chronic heart
      failure. The understanding of the physiopathology of myocardial inflammation is
      crucial for a timely diagnosis and for the control of the tissue damage, which
      may occur in some cases of IM. Of note, some experimental studies suggest that
      dilated cardiomyopathy could be a consequence of untreated IM. However, further
      research is required to address the molecular mechanisms that may link these two
      clinical entities. Here we review the mechanisms involved in the regulation at
      different levels of the immune response during IM, with a special focus on
      diagnostic and therapeutic perspectives of molecules that have been linked to the
      development of IM and the resulting chronic heart diseases. 

PMID- 24450514
TI  - Optimization of peptides that target human thymidylate synthase to inhibit
      ovarian cancer cell growth.
AB  - Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5
      fluorouracil (5-FU) that inhibit the protein by binding at its active site.
      Prolonged administration of these drugs causes TS overexpression, leading to drug
      resistance. The peptide lead, LR (LSCQLYQR), allosterically stabilizes the
      inactive form of the protein and inhibits ovarian cancer (OC) cell growth with
      stable TS and decreased dihydrofolate reductase (DHFR) expression. To improve TS
      inhibition and the anticancer effect, we have developed 35 peptides by modifying
      the lead. The d-glutamine-modified peptide displayed the best inhibition of
      cisplatin-sensitive and -resistant OC cell growth, was more active than LR and 5
      FU, and showed a TS/DHFR expression pattern similar to LR. Circular dichroism
      spectroscopy and molecular dynamics studies provided a molecular-level rationale
      for the differences in structural preferences and the enzyme inhibitory
      activities. By combining target inhibition studies and the modulation pattern of
      associated proteins, this work avenues a concept to develop more specific
      inhibitors of OC cell growth and drug leads. 

PMID- 24450515
TI  - Management of metastatic kidney cancer in the era of personalized medicine.
AB  - Patients with localized renal cell cancer (RCC) are often cured following
      surgical resection. However, a significant proportion of patients will experience
      recurrence or present with metastatic disease at distant sites and may be deemed
      incurable. The worldwide incidence of RCC is rising, affecting more than 271,000
      people and resulting in 116,000 deaths each year. Unfortunately, advanced RCC is
      typically resistant to classical chemotherapy and radiotherapy. Previously, non
      specific immunotherapies such as interleukin-2 and interferon were used in hopes
      of improving cancer immunity, leading to rare but durable responses. However,
      enthusiasm for these immunotherapies has waned due to limited patient responses,
      their excessive toxicities, and the emergence of alternative targeted therapies
      that have resulted in improved clinical endpoints for patients with metastatic
      RCC (mRCC). Strides in targeted treatment can be attributed to an improved
      understanding of the molecular underpinnings that cause and drive the progression
      of renal cell cancers. More recently, interest in immunotherapies has resurfaced,
      as agents inhibiting specific checkpoints involved in cancer immune evasion have
      demonstrated promising activity in patients with mRCC. Here we review the novel
      targeted agents, biomarkers and immunotherapies that promise to change the
      clinical outcomes for patients with advanced RCC.

PMID- 24450518
TI  - New imaging techniques for more effective treatment in glioblastoma.

PMID- 24450519
TI  - Erectile dysfunction.
AB  - In the past 30 years, advances in basic science have been instrumental in the
      evolution of the male sexual health treatment paradigm from a psychosexual model
      to a new model, which includes oral and intracavernosal injection
      pharmacotherapy, vacuum constriction devices and penile prostheses for the
      treatment of erectile dysfunction. This progress has coincided with an increased
      understanding of the nature of male sexual health problems, and epidemiological
      data that confirm that these problems are widely prevalent and the source of
      considerable morbidity, both for individuals and within relationships. 

PMID- 24450521
TI  - Twenty-year trends in benzodiazepine dispensing in the Australian population.
AB  - AIM: Considerable concern has been expressed about overprescribing of
      benzodiazepines and related harms. Past analyses have relied on World Health
      Organization-defined daily doses (DDD) which are sometimes out of keeping with
      clinical usage. This study examines 20-year (1992-2011) trends of benzodiazepine
      dispensing in Australia using both DDD and Ashton equivalent dose. METHODS: Data
      from the Drug Utilisation Sub-Committee and the Pharmaceutical Benefits Scheme
      (PBS) website were analysed. Trends in number of prescriptions, DDD/1000
      people/day and DDD/prescription were examined over time, and between
      states/territories. RESULTS: In the 20-year period, 174 080 904 scripts were
      recorded, with temazepam the most dispensed benzodiazepine (35% of scripts),
      followed by diazepam (23%). Overall recorded utilisation fell from 27.7 DDD/1000
      people/day in 1992 to 20.8 in 2011 (24.9% decrease). There were striking changes
      in use of individual benzodiazepines over time, with reductions in oxazepam and
      flunitrazepam and dramatic increases in alprazolam. Since 1998, there has been a
      steady increase, albeit modest, in per script DDD. The DDD/1000 people/day for
      items dispensed through PBS/Repatriaton-PBS was highest in Tasmania and lowest in
      Northern Territory. CONCLUSION: Despite a modest overall decline in the amount of
      benzodiazepine dispensed, the level of use is still likely to reflect relative
      over-prescribing given the paucity of accepted indications for long-term use.
      Since 1998, there was a polynomial increase in quantity dispensed per script. The
      WHO-defined DDD for clonazepam seems inappropriate and could impede monitoring of
      its abuse. Other problems include lack of national data for medications not
      subsidised on PBS/Repatriation PBS. A broad policy approach is required, not one
      which targets only one particular benzodiazepine.

PMID- 24450520
TI  - Australians' knowledge and perceptions of direct-to-consumer personal genome
      testing.
AB  - BACKGROUND: As direct-to-consumer personal genome testing (DTC-PGT) is
      increasingly available in Australia, knowledge of Australians' perceptions and
      attitudes towards this technology is needed in order to assess the (potential)
      impact it might have on the Australian public and healthcare system. AIMS: To
      explore the knowledge and perceptions of DTC-PGT in an Australian sample.
      METHODS: An online survey asking about knowledge and perceptions of DTC-PGT,
      undertaken between October 2011 and April 2012, of 270 Australian residents.
      Results were analysed using SAS. RESULTS: Our study found limited consumer
      knowledge of, and interest in, pursuing DTC-PGT in Australia. Ninety-three per
      cent of respondents correctly identified DTC-PGT as available to consumers
      directly, but only 40% correctly identified its availability in Australia. When
      asked about the content and value of the information DTC-PGT provides, the
      majority of respondents indentified that DTC-PGT could provide information about
      one's health and/or ancestry (82% and 74%). Additionally, respondents indicated
      they believed this information to be equally important as non-genetic information
      about one's ancestry and health. CONCLUSION: While a minority of respondents
      expressed an intention to pursue DTC-PGT (27%), the majority of respondents,
      irrespective of whether they wished to pursue it or not, believed that genetic
      information was as important as non-genetic information in regards to their
      health and their ancestry. The value ascribed to genetic information suggests
      that genetics plays a role in people's lives, and that further qualitative
      research could explore the ways in which people might use and understand the
      genetic information provided by DTC-PGT.

PMID- 24450522
TI  - Cardiac sarcoidosis: the Christchurch experience.
AB  - BACKGROUND AND AIMS: To present an overview of the diagnosis, treatment and
      outcomes of patients with cardiac sarcoidosis managed in Christchurch Hospital,
      New Zealand. METHODS: A retrospective review of patients with cardiac sarcoidosis
      at Christchurch Hospital from January 2005 to December 2012. RESULTS: Eighteen
      patients were identified with cardiac sarcoidosis. All the 12 patients that
      underwent cardiac magnetic resonance imaging (CMR) had abnormal scans.
      Angiotensin-converting enzyme (ACE) levels were elevated in 4 of 16 patients and
      troponin (cTn) was elevated in 5 of 15 patients. Endomyocardial biopsies were
      diagnostic in two of six patients. The principal causes for presentation related
      to symptomatic high-grade atrioventricular conduction block and congestive heart
      failure with six patients in each of these groups. In addition, three patients
      presented with ventricular tachycardia and the remaining three patients presented
      with atrial fibrillation, recurrent presyncope without proven heart block and an
      asymptomatic persistent elevation of cardiac troponin. Seven patients had pre
      existing, extra-cardiac sarcoidosis and a concomitant diagnosis was made in a
      further eight cases. Three patients had isolated cardiac involvement at
      presentation. Sixteen patients received immunosuppressive therapy. Twelve
      patients had cardiac devices implanted; five pacemakers, five defibrillators and
      two resynchronising pacemaker defibrillators. During follow up for 0.1-30.8
      years, median 4.8 years, two patients died. CONCLUSIONS: In our patients CMR
      demonstrated high diagnostic sensitivity, while biomarkers (ACE and cTn) were
      frequently within the normal reference range. Cardiac sarcoidodis caused major
      arrhythmias or heart failure in the majority of patients. Most patients were
      treated with immunosuppression and cardiac device therapy. Long-term mortality
      was lower than previously reported.

PMID- 24450523
TI  - Embedding research in clinical practice: differences in attitudes to research
      participation among clinicians in a tertiary teaching hospital.
AB  - Despite a drive to increase research in healthcare settings, clinician
      participation in research remains infrequent. This paper describes an online
      survey comparing attitudes with research participation among clinicians (doctors,
      nurses and allied health professionals) at an Australian tertiary children's
      hospital. Differences between professional groups support the existence of
      different professional cultures surrounding research, suggesting that multiple
      strategies are required to improve participation in research. 

PMID- 24450524
TI  - Successful treatment of Erdheim-Chester disease with combination of interleukin-1
      targeting drugs and high-dose glucocorticoids.
AB  - Erdheim-Chester disease (ECD) is a rare histocytic disorder. We report a case of
      a 45-year-old male ECD patient with severe clinical manifestation (urinary
      obstruction due to retroperitoneal mass with hydronephrosis, involvement of long
      bones) and central nervous system involvement (hemiparesis, aphasia and diabetes
      insipidus). Diagnosis was confirmed by typical clinical, radiological and
      histological findings. Under immunosuppressive therapy with prednisolone and
      interleukin-1A receptor antagonist (Anakinra, Kineret, Swedish Orphan Biovitrum
      AB, Stockholm, Sweden), a rapid improvement of the patients' symptoms and
      condition was observed. This is the first report of a successful combination
      therapy of Anakinra and glucocorticoids. Furthermore, current literature about
      ECD and treatment options are discussed. 

PMID- 24450525
TI  - Inadequate resuscitation documentation in older patients' clinical case notes.
AB  - This research examined the quality of resuscitation decisions documented in the
      clinical notes of 99 older patients within 48 h of admission. Only 34 had current
      documentation that was frequently inconsistent and ambiguous, leaving patients at
      risk of receiving inappropriate and unwanted resuscitation. Clear guidelines with
      community input to guide the implementation and documentation of end-of-life
      decisions are essential. 

PMID- 24450526
TI  - Use of infliximab and other biologics in Behcet disease.
AB  - Behcet disease is a multisystem vasculitis characterised by recurrent oral
      ulceration in conjunction with other manifestations. Neurological involvement or
      neuro-Behcet disease is not common, but typically affects young men at its onset
      between the ages of 20 and 40 with significant long-term morbidity and mortality.
      There is substantial case literature to support the use of tumour necrosis factor
      antagonists, notably infliximab, in the treatment of neuro-Behcet disease. 

PMID- 24450527
TI  - Practical aspects of telehealth: doctor-patient relationship and communication.
AB  - The fourth in a series of articles about the practical aspects of telehealth,
      this paper provides advice and information for specialists to communicate
      effectively with patients during a telehealth video consultation. 

PMID- 24450528
TI  - Late-onset type 1 diabetes in Pasifika migrants living in Auckland.

PMID- 24450529
TI  - Baroreceptor failure related to bilateral carotid artery disease: an uncommon
      cause of labile hypertension.

PMID- 24450530
TI  - Purple toes syndrome following stroke thrombolysis and warfarin therapy.

PMID- 24450531
TI  - Whose responsibility is it to assess cardiovascular risk in patients with
      rheumatoid arthritis?

PMID- 24450532
TI  - Patient perspective: what would Donabedian say?

PMID- 24450533
TI  - A modular computational framework for automated peak extraction from ion mobility
      spectra.
AB  - BACKGROUND: An ion mobility (IM) spectrometer coupled with a multi-capillary
      column (MCC) measures volatile organic compounds (VOCs) in the air or in exhaled
      breath. This technique is utilized in several biotechnological and medical
      applications. Each peak in an MCC/IM measurement represents a certain compound,
      which may be known or unknown. For clustering and classification of measurements,
      the raw data matrix must be reduced to a set of peaks. Each peak is described by
      its coordinates (retention time in the MCC and reduced inverse ion mobility) and
      shape (signal intensity, further shape parameters). This fundamental step is
      referred to as peak extraction. It is the basis for identifying discriminating
      peaks, and hence putative biomarkers, between two classes of measurements, such
      as a healthy control group and a group of patients with a confirmed disease.
      Current state-of-the-art peak extraction methods require human interaction, such
      as hand-picking approximate peak locations, assisted by a visualization of the
      data matrix. In a high-throughput context, however, it is preferable to have
      robust methods for fully automated peak extraction. RESULTS: We introduce PEAX, a
      modular framework for automated peak extraction. The framework consists of
      several steps in a pipeline architecture. Each step performs a specific sub-task
      and can be instantiated by different methods implemented as modules. We provide
      open-source software for the framework and several modules for each step.
      Additionally, an interface that allows easy extension by a new module is
      provided. Combining the modules in all reasonable ways leads to a large number of
      peak extraction methods. We evaluate all combinations using intrinsic error
      measures and by comparing the resulting peak sets with an expert-picked one.
      CONCLUSIONS: Our software PEAX is able to automatically extract peaks from MCC/IM
      measurements within a few seconds. The automatically obtained results keep up
      with the results provided by current state-of-the-art peak extraction methods.
      This opens a high-throughput context for the MCC/IM application field. Our
      software is available at http://www.rahmannlab.de/research/ims.

PMID- 24450534
TI  - First-principles study on site preference and 4f -> 5d transitions of Ce(3+) in
      Sr3AlO4F.
AB  - The local structures and 4f -> 5d transition energies of Ce(3+) located on the
      two crystallographic strontium sites of Sr3AlO4F, with charge compensation by
      means of nearby sodium substitutions for strontium (NaSr') or oxygen
      substitutions for coordinating fluorine (OF'), have been studied using the
      density functional theory (DFT) within the supercell model and the wave function
      based embedded cluster calculations, respectively. The DFT total energy
      calculations show that Ce(3+) prefers strongly to occupy the eight-coordinated
      (Sr2) site over the ten-coordinate (Sr1) site. On the basis of the results from
      embedded cluster calculations at the CASPT2 level with the spin-orbit effect, the
      experimentally observed excitation bands are identified in association with the
      charge-compensated cerium centers. Especially, the two bands observed at ~404 and
      ~440 nm have been both assigned to the Ce(3+) located at the Sr2 sites but with
      compensation by one and two nearest-neighbor OF' substitutions, respectively,
      rather than to the Ce(3+) on the Sr1 and the Sr2 sites, respectively, as proposed
      earlier. Furthermore, the structural and electronic reasons for the red shift of
      the lowest 4f -> 5d transition caused by coordinating OF' substitutions are
      analyzed in terms of the variations in centroid energy and crystal-field
      splitting of the 5d(1) configuration with the local environment. Finally, the
      thermal quenching of 5d luminescence at relatively high Ce(3+) concentrations is
      discussed on the basis of the electronic properties calculated with the hybrid
      DFT method. 

PMID- 24450535
TI  - Patterns of cannabis use and prospective associations with health issues among
      young males.
AB  - BACKGROUND AND AIMS: To test prospective associations between cannabis disorder
      symptoms/frequency of cannabis use and health issues and to investigate stability
      versus transience in cannabis use trajectories. DESIGN: Two waves of data
      collection from the longitudinal Cohort Study on Substance Use Risk Factors (C
      SURF). SETTING: A representative sample of young Swiss men in their early 20s
      from the general population. PARTICIPANTS: A total of 5084 young men (mean age
      19.98 +/- 1.19 years at time 1). MEASUREMENTS: Cannabis use (life-time use,
      frequency of use, cannabis disorder symptoms) and self-reported measures of
      health issues (depression, mental/physical health, health consequences) were
      assessed. Significant changes in cannabis use were tested using t-test/Wilcoxon's
      rank test for paired data. Cross-lagged panel models provided evidence regarding
      longitudinal associations between cannabis use and health issues. FINDINGS: Most
      of the participants (84.5%) remained in the same use category and cannabis use
      kept to similar levels at times 1 and 2 (P = 0.114 and P = 0.755; average of 15
      +/- 2.8 months between times 1 and 2). Cross-lagged panel models showed that
      cannabis disorder symptoms predicted later health issues (e.g. depression, beta =
      0.087, P < 0.001; health consequences, beta = 0.045, P < 0.05). The reverse paths
      from health issues to cannabis disorder symptoms and the cross-lagged panel model
      between frequency of cannabis use and health issues were non-significant.
      CONCLUSIONS: Patterns of cannabis use showed substantial continuity among young
      Swiss men in their early 20s. The number of symptoms of cannabis use disorder,
      rather than the frequency of cannabis use, is a clinically important measure of
      cannabis use among young Swiss men.

PMID- 24450536
TI  - Prospective registry of symptomatic severe aortic stenosis in octogenarians: a
      need for intervention.

PMID- 24450537
TI  - Immunotherapy for malignant pleural mesothelioma. Current status and future
      prospects.
AB  - Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is
      frequently resistant to conventional therapies. Immunotherapy is a promising
      investigational approach for MPM that has shown some evidence of clinical benefit
      in select patients. However, tumor-induced immunosuppression is likely a major
      impediment to achieving optimal clinical responses to immunotherapeutic
      intervention. MPM contains a variable degree of infiltrating T-regulatory cells
      and M2 macrophages, which are believed to facilitate tumor evasion from the host
      immune system. Additional immunosuppressive factors identified in other human
      tumor types, such as tumor-associated programmed death ligand-1 expression, may
      be relevant for investigation in MPM. Conventional cytoreductive therapies, such
      as radiation, chemotherapy, and surgery, may play a critical role in successful
      immunotherapeutic strategies by ablating intratumoral and/or systemic
      immunosuppressive factors, thus creating a host environment more amenable to
      immunotherapy. This article reviews the immunotherapeutic approaches being
      evaluated in patients with MPM and discusses how immunotherapy might be
      rationally combined with conventional tumor cytoreductive therapies for this
      disease.

PMID- 24450538
TI  - The impact of shift duration on the efficacy and tolerability of armodafinil in
      patients with excessive sleepiness associated with shift work disorder.
AB  - OBJECTIVE: To examine the impact of night-shift duration (<=9 hours or >9 hours)
      on efficacy and tolerability of armodafinil in patients with shift work disorder
      (SWD). METHODS: This was a post hoc analysis of a 6 week, multicenter,
      randomized, double-blind, placebo-controlled, parallel-group study. Shift workers
      with diagnosed SWD and late-in-shift sleepiness (between 4 am and 8 am, including
      the commute home) received armodafinil 150 mg or placebo before their night
      shift. RESULTS: Proportion of patients with at least minimal improvement in late
      in-shift sleepiness, late-in-shift Clinical Global Impressions-Change (CGI-C)
      rating and Karolinska Sleepiness Scale (KSS), as well as overall Global
      Assessment of Functioning (GAF) scale and modified Sheehan Disability Scale (SDS
      M), were assessed at baseline and final visit. RESULTS: Of the 383 patients
      enrolled, 279 (73%) worked shifts <=9 hours and 104 (27%) worked shifts >9 hours.
      A greater percentage of patients receiving armodafinil had at least minimal
      improvement in late-in-shift CGI-C (<=9 hours: 78% vs 60%, P = 0.0017; >9 hours:
      77% vs 46%, P = 0.0020) regardless of shift duration. Armodafinil patients also
      demonstrated significantly greater improvements in GAF score (<=9 hours: 9.5 vs
      5.4, P < 0.0001; >9 hours: 9.6 vs 4.3, P = 0.0019) and KSS score (<=9 hours: -2.9
      vs -1.9, P = 0.0002; >9 hours: -2.8 vs -1.6, P = 0.00 28). Improvement in SDS-M
      composite score was significantly greater for armodafinil patients working >9
      hours (-6.8 vs -2.7, P = 0.0086). Headache was the most frequent adverse event in
      all treatment groups. CONCLUSIONS: Patients receiving armodafinil had
      significantly greater improvements in late-in-shift clinical condition and in
      wakefulness and overall global functioning than did placebo-treated patients,
      regardless of shift duration. Prospectively designed, randomized clinical trials
      that include objective measures of sleepiness are needed to support these
      findings.

PMID- 24450539
TI  - Does dental indifference influence the oral health-related quality of life of
      prisoners?
AB  - OBJECTIVES: Prisoners have worse oral health and greater unmet dental treatment
      needs than the general population. However, little is known about the impact of
      the mouth, or attitudes such as dental indifference and consequent patterns of
      dental service use in this disadvantaged group. The aim was to determine whether
      dental indifference was associated with the oral health-related quality of life
      (OHQoL) of prisoners using Andersen's behavioural model of service utilization as
      the theoretical framework. METHODS: The sample was male prisoners aged 20-35
      years attending three prisons in the north of England. Participants took part in
      interviews and oral examinations. The variables were selected to populate
      Andersen's model including: predisposing characteristics (socioeconomic status),
      enabling resources (dental indifference and dental attendance patterns before
      prison), perceived need (perceived treatment need, satisfaction with appearance
      of teeth, global rating of oral health), evaluated need (number of decayed
      teeth), health behaviours (use of dental services while in prison) and health
      outcomes (OHQoL). Structural equation modelling was used to estimate direct and
      indirect pathways between variables. RESULTS: Of the 700 men approached, 659
      completed the interview and clinical examination. Worse OHQoL was associated with
      less dental indifference (i.e. greater interest in oral health), previous regular
      use of dental services, perceived need for treatment and use of prison dental
      services. The number of decayed teeth and predisposing factors such as
      qualifications and employment did not predict OHQoL. CONCLUSIONS: Dental
      indifference was related to the OHQoL of prisoners in addition to previous
      regular use of dental services, a perceived need for treatment and use of dental
      services while in prison. Dental services in prisons might incorporate methods to
      address dental indifference in their attempts to improve oral health. The
      findings also have general implications for the assessment of population oral
      health needs.

PMID- 24450540
TI  - Comparative meta-RNA-seq of the vaginal microbiota and differential expression by
      Lactobacillus iners in health and dysbiosis.
AB  - BACKGROUND: Bacterial vaginosis (BV), the most common vaginal condition of
      reproductive-aged women, is associated with a highly diverse and heterogeneous
      microbiota. Here we present a proof-of-principle analysis to uncover the function
      of the microbiota using meta-RNA-seq to uncover genes and pathways that
      potentially differentiate healthy vaginal microbial communities from those in the
      dysbiotic state of bacterial vaginosis (BV). RESULTS: The predominant organism,
      Lactobacillus iners, was present in both conditions and showed a differing
      expression profile in BV compared to healthy. Despite its minimal genome, L.
      iners differentially expressed over 10% of its gene complement. Notably, in a BV
      environment L. iners increased expression of a cholesterol-dependent cytolysin,
      and of mucin and glycerol transport and related metabolic enzymes. Genes
      belonging to a CRISPR system were greatly upregulated suggesting that
      bacteriophage influence the community. Reflective of L. iners, the bacterial
      community as a whole demonstrated a preference for glycogen and glycerol as
      carbon sources under BV conditions. The predicted end-products of metabolism
      under BV conditions include an abundance of succinate and other short-chain fatty
      acids, while healthy conditions are predicted to largely contain lactic acid.
      CONCLUSIONS: Our study underscores the importance of understanding the functional
      activity of the bacterial community in addition to characterizing the population
      structure when investigating the human microbiome.

PMID- 24450541
TI  - Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer
      initiating cells.
AB  - The aim of the present study was to establish cancer stem-like cell/cancer
      initiating cell (CSC/CIC)-targeting immunotherapy. The CSC/CIC are thought to be
      essential for tumor maintenance, recurrence and distant metastasis. Therefore
      they are reasonable targets for cancer therapy. In the present study, we found
      that a heat shock protein (HSP) 40 family member, DnaJ (Hsp40) homolog, subfamily
      B, member 8 (DNAJB8), is preferentially expressed in CSC/CIC derived from
      colorectal cancer (CRC) cells rather than in non-CSC/CIC. Overexpression of
      DNAJB8 enhanced the expression of stem cell markers and tumorigenicity,
      indicating that DNAJB8 has a role in CRC CSC/CIC. A DNAJB8-specific cytotoxic T
      lymphocyte (CTL) response could be induced by a DNAJB8-derived antigenic peptide.
      A CTL clone specific for DNAJB8 peptide showed higher killing activity to CRC
      CSC/CIC compared with non-CSC/CIC, and CTL adoptive transfer into CRC CSC/CIC
      showed an antitumor effect in vivo. Taken together, the results indicate that
      DNAJB8 is expressed and has role in CRC CSC/CIC and that DNAJB8 is a novel target
      of CRC CSC/CIC-targeting immunotherapy. 

PMID- 24450542
TI  - Physical activity in adolescents with psychiatric disorders and in the general
      population.
AB  - BACKGROUND: Adults who suffer from psychiatric disorders report low levels of
      physical activity and the activity levels differ between disorders. Less is known
      regarding physical activity across psychiatric disorders in adolescence. We
      investigate the frequency and type of physical activity in adolescent psychiatric
      patients, compared with adolescents in the general population. METHODS: A total
      of 566 adolescent psychiatric patients aged 13-18 years who participated in the
      CAP survey, Norway, were compared to 8173 adolescents aged 13-19 years who
      participated in the Nord-Trondelag Health Study, Young-HUNT 3, Norway. All
      adolescents completed a questionnaire, including questions about physical
      activity and participation in team and individual sports. RESULTS: Approximately
      50% of adolescents with psychiatric disorders and 25% of the population sample
      reported low levels of physical activity. Within the clinical sample, those with
      mood disorders (62%) and autism spectrum disorders (56%) were the most inactive
      and those with eating disorders (36%) the most active. This pattern was the same
      in individual and team sports. After multivariable adjustment, adolescents with a
      psychiatric disorder had a three-fold increased risk of lower levels of physical
      activity, and a corresponding risk of not participating in team and individual
      sports compared with adolescents in the general population. CONCLUSIONS: Levels
      of physical activity were low in adolescent psychiatric patients compared with
      the general population, yet activity levels differed considerably between various
      disorders. The findings underscore the importance of assessing physical activity
      in adolescents with psychiatric disorders and providing early intervention to
      promote mental as well as physical health in this early stage of life.

PMID- 24450543
TI  - 9-arylidene-9H-fluorene-containing polymers for high efficiency polymer solar
      cells.
AB  - 9-Arylidene-9H-fluorene containing donor-acceptor (D-A) alternating polymers P1
      and P2 were synthsized and used for the fabrication of polymer solar cells
      (PSCs). High and low molecular weight P1 (HMW-P1 and LMW-P1) and high molecular
      weight P2 were prepared to study the influence of molecular weight and the
      position of alkoxy chains on the photovoltaic performance of PSCs. HMW-P1:PC71BM
      based PSCs fabricated from 1,2-dichlorobenzene (DCB) solutions showed a power
      conversion efficiency (PCE) of 6.26%, while LMW-P1:PC71BM-based PSCs showed poor
      photovoltaic performance with a PCE of only 2.75%. PCE of HMW-P1:PC71BM-based
      PSCs was further increased to 6.52% with the addition of 1,8-diiodooctane (DIO)
      as the additive. Meanwhile, PCE of only 2.51% was obtained for P2:PC71BM-based
      PSCs. The results indicated that the position of alkoxy substituents on the 9
      arylidene-9H-fluorene unit and the molecular weight of polymers are very crucial
      to the photovoltaic performance of PSCs. 

PMID- 24450544
TI  - Unavailability of liver triacylglycerol increases serum cholesterol concentration
      induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats.
AB  - BACKGROUND: Exogenously hypercholesterolemic (ExHC) rats develop
      hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary
      cholesterol is loaded. The responsible gene Smek2 was identified via linkage
      analysis using the original strain Sprague-Dawley (SD) rats. In this study, we
      compared SD and ExHC rats to investigate a relationship between
      hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats.
      METHODS: Male 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1
      week. Serum and liver parameters were analyzed. Gene expression and enzyme
      activities related to TAG metabolism were also assessed. RESULTS: We reproducibly
      observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than
      in SD rats. Golgi apparatus in the livers of ExHC rats secreted beta-very-low
      density lipoprotein (beta-VLDL) that had higher cholesterol ester (CE) and lower
      TAG content than those in the beta-VLDL secreted by SD rats. Gene expression
      related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD
      rats. Enzymatic activities for fatty acid synthesis were also relatively lower in
      ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC
      rats showed that these CEs were not modified after secretion from the liver
      despite the similar activities of serum lecithin-cholesterol acyltransferase
      (LCAT) in ExHC rats to those in SD rats. CONCLUSIONS: Low production of liver TAG
      and secretion of CE-rich, TAG-poor beta-VLDL without modification by LCAT in the
      circulation contributed to hypercholesterolemia induced by dietary cholesterol in
      ExHC rats.

PMID- 24450545
TI  - Drugs for addiction: a therapeutic area in need of a 'shot in the arm'.

PMID- 24450546
TI  - Editors' pick 2013.

PMID- 24450547
TI  - Evaluation and simulation of silver and copper nanoparticle migration from
      polyethylene nanocomposites to food and an associated exposure assessment.
AB  - Silver nanoparticles (nanosilver) and copper nanoparticles (nanocopper) exhibit
      antimicrobial activity and have been incorporated into polymers to create
      antimicrobial packaging materials. Their use in conjunction with food has caused
      concerns regarding the potential risk of particle migration, resulting in human
      exposure to nanoparticles. A migration experiment was carried out to investigate
      the effect of time and temperature on the migration of nanosilver and nanocopper
      particles from polyethylene (PE) nanocomposites to boneless chicken breasts.
      Migration of silver ranged from 0.003 to 0.005 mg/dm2, while migration of copper
      ranged from 0.024 to 0.049 mg/dm2, for a set of four different scenarios
      representing typical storage conditions. Effects of time and temperature were not
      significant (p > 0.1). A migration and exposure model was developed on the basis
      of mathematical relationships defining migratability and subsequent migratables
      using the Williams-Landel-Ferry equation for time-temperature superposition. The
      results of the model accurately predicted the nanosilver levels detected in the
      laboratory migration tests (R values ranging from 0.43 to 0.99); however, the
      model was less accurate in predicting nanocopper levels (R values ranging from
      0.65 to 0.99), probably because of the highly variable background levels of
      copper observed in the real food matrix. The 95th percentile of the simulated
      human exposure to nanosilver based on laboratory experimental results of four
      scenarios ranged from 5.89 * 10-5 to 8.9 * 10-5 mg kg(bw)-1 day-1. For the
      measured migration of copper under the same storage conditions, the exposure
      ranged from 2.26 * 10-5 to 1.17 * 10-4 mg kg(bw)-1 day-1. This study highlights
      the potential migration of nanoparticles from PE composite packaging to a food
      material and the potential for simulation models to accurately capture this
      migration potential; however, variable background levels of copper in the food
      matrix can make prediction more difficult for trace migration of nanocopper.

PMID- 24450548
TI  - Cost-effectiveness of asenapine in the treatment of bipolar disorder in Canada.
AB  - BACKGROUND: Bipolar disorder (BPD) is prevalent and is associated with a
      significant economic burden. Asenapine, the first tetracyclic antipsychotic
      approved in Canada for the treatment of BPD, has shown a comparable efficacy
      profile to other atypical antipsychotics. In addition, it is associated with a
      favourable metabolic profile and minimal weight gain potential. This study aimed
      to assess the economic impact of asenapine compared to olanzapine in the
      treatment of BPD in Canada. METHODS: A decision tree combined with a Markov model
      was constructed to assess the cost-utility of asenapine compared with olanzapine.
      The decision tree takes into account the occurrence of extrapyramidal symptoms
      (EPS), the probability of switching to a different antipsychotic, and the
      probability of gaining weight. The Markov model takes into account long-term
      metabolic complications including diabetes, hypertension, coronary heart diseases
      (CHDs), and stroke. Analyses were conducted from both a Canadian Ministry of
      Health (MoH) and a societal perspective over a five-year time horizon with yearly
      cycles. RESULTS: In the treatment of BPD, asenapine is a dominant strategy over
      olanzapine from both a MoH and a societal perspective. In fact, asenapine is
      associated with lower costs and more quality-adjusted life years (QALYs). Results
      of the probabilistic sensitivity analysis indicated that asenapine remains a
      dominant strategy in 99.2% of the simulations, in both a MoH and a societal
      perspective, and this result is robust to the many deterministic sensitivity
      analyses performed. CONCLUSIONS: This economic evaluation demonstrates that
      asenapine is a cost-effective strategy compared to olanzapine in the treatment of
      BPD in Canada.

PMID- 24450555
TI  - Growing research on sarcopenia in Asia.

PMID- 24450554
TI  - Generation of divergent uroplakin tetraspanins and their partners during
      vertebrate evolution: identification of novel uroplakins.
AB  - BACKGROUND: The recent availability of sequenced genomes from a broad array of
      chordates (cephalochordates, urochordates and vertebrates) has allowed us to
      systematically analyze the evolution of uroplakins: tetraspanins (UPK1a and UPK1b
      families) and their respective partner proteins (UPK2 and UPK3 families).
      RESULTS: We report here: (1) the origin of uroplakins in the common ancestor of
      vertebrates, (2) the appearance of several residues that have statistically
      significantly positive dN/dS ratios in the duplicated paralogs of uroplakin
      genes, and (3) the existence of strong coevolutionary relationships between
      UPK1a/1b tetraspanins and their respective UPK2/UPK3-related partner proteins.
      Moreover, we report the existence of three new UPK2/3 family members we named
      UPK2b, 3c and 3d, which will help clarify the evolutionary relationships between
      fish, amphibian and mammalian uroplakins that may perform divergent functions
      specific to these different and physiologically distinct groups of vertebrates.
      CONCLUSIONS: Since our analyses cover species of all major chordate groups this
      work provides an extremely clear overall picture of how the uroplakin families
      and their partner proteins have evolved in parallel. We also highlight several
      novel features of uroplakin evolution including the appearance of UPK2b and 3d in
      fish and UPK3c in the common ancestor of reptiles and mammals. Additional studies
      of these novel uroplakins should lead to new insights into uroplakin structure
      and function.

PMID- 24450556
TI  - Age-dependent changes in skeletal muscle mass and visceral fat area in Japanese
      adults from 40 to 79 years-of-age.
AB  - AIM: The age-dependent loss of skeletal muscle mass is highly concerning in
      diverse aging populations. However, age-dependent changes in muscle mass and the
      visceral fat area have not been well documented in Asian populations. The aim of
      the present study was to evaluate the age-dependent changes in skeletal muscle
      mass and the visceral fat area in Japanese adults from 40 to 79 years-of-age.
      METHODS: This was a cross-sectional study. Healthy men (n = 16,379) and women (n
      = 21,660) aged 40-79 years participated in the present study. The skeletal muscle
      mass and visceral fat area were measured in the study participants by
      bioelectrical impedance. The muscle mass data were converted into the skeletal
      muscle mass index (SMI) by dividing the weight by the height squared (kg/m(2)).
      RESULTS: The SMI showed an age-dependent decrease in both sexes. Between 40 and
      79 years, the total SMI decreased by 10.8% in men and by 6.4% in women. The arm
      SMI decreased by 12.6% in men and 4.1% in women, and the leg SMI decreased by
      10.1% in men and by 7.1% in women in the same period. In contrast, the visceral
      fat area showed an age-dependent increase in both sexes. The visceral fat area
      increased by 42.9% in men and by 65.3% in women. The multiple regression analysis
      showed that the SMI was negatively associated with visceral obesity in both
      sexes. CONCLUSIONS: In Japanese adults, sex-specific changes in skeletal muscle
      mass are more prominent in the arm than in the leg. Furthermore, the age
      dependent increases in visceral adipose tissue might lead to loss of skeletal
      muscle mass.

PMID- 24450557
TI  - Incidence, reversibility, risk factors and the protective effect of high body
      mass index against sarcopenia in community-dwelling older Chinese adults.
AB  - AIM: We examined the incidence and the reversibility of sarcopenia and their
      associated factors over a 4-year period using the European Working Group on
      Sarcopenia in Older People (EWGSOP) criteria. METHODS: A total of 4000 community
      dwelling older adults aged >= 65 years were evaluated for which detailed
      information regarding demographics, socioeconomic, medical history, lifestyle,
      and clinical factors were documented at baseline, 2 years, and 4 years later.
      Sarcopenia was defined according to the EWGSOP algorithm. Incident sarcopenia and
      its reversibility were documented at each follow-up year, and related to possible
      factors. RESULTS: At baseline, of the 4000 participants, 361(9.0%) had
      sarcopenia. Between baseline and 2-year follow-up, 6.0% of the participants
      without sarcopenia at baseline had developed sarcopenia, and 18.8% of the
      initially sarcopenic participants had reverted to normal.Between baseline and 4
      year follow-up, the corresponding figures were 6.3% and 14.1%, respectively. The
      average annual incidence over 4 years was 3.1%. After multivariate adjustments,
      older age, female sex, presence of chronic obstructive pulmonary disease,
      presence of stroke, lower physical activity levels, presence of instrumental
      activities of daily living impairments, and lower body mass index were associated
      with incident sarcopenia, whereas younger age, female sex, higher body mass index
      and absence of instrumental activities of daily living impairments, but not
      physical activity,were associated with its reversibility. Protein and vitamin D
      intake were not significantly associated with sarcopenia incidence or its
      reversibility [corrected]. CONCLUSION: Sarcopenia incidence increases with age,
      but is potentially reversible in a Chinese elderly population. High body mass
      index is protective against sarcopenia incidence and its reversibility.
      Increasing physical activity and maintaining a healthy weight could be beneficial
      in the prevention of sarcopenia.

PMID- 24450558
TI  - Sarcopenia and sarcopenic obesity among men aged 80 years and older in Beijing:
      prevalence and its association with functional performance.
AB  - AIM: Sarcopenia and sarcopenic obesity are significant associative factors for
      functional impairment related to aging. The main aim of the present study was to
      investigate the prevalence of sarcopenia and sarcopenic obesity, and their
      associations with functional status among men aged 80 years and older in Beijing.
      METHODS: A total of 75 young healthy volunteers, and 101 older men aged 80 years
      and older participated in the present study. Demographic characteristics,
      anthropometry, skeletal muscle mass measured by dual X-ray absorptiometry (DXA),
      6-m gait speed and handgrip strength were collected. Relative appendicular
      skeletal muscle index (RASM) and percentage skeletal muscle index (SMI) were
      obtained. RESULTS: Overall, the prevalence of sarcopenia was 45.7% by using RASM.
      By the weight-adjusted skeletal muscle index definition (SMI), the prevalence of
      sarcopenia was 53.2%. The prevalence of sarcopenic obesity was lower by using
      RASM than SMI (4.9% vs 11.5%, P < 0.05). When we compared the sarcopenia
      prevalence (%) in obese participants, it was also remarkably lower by using RASM
      (40.0%) than SMI (95.0%). By using either RASM or SMI, gait speed was of no
      significant difference among the pure sarcopenia group, pure obese group and
      sarcopenic obesity group (0.76 +/- 0.27 vs 0.82 +/- 0.37 vs 0.82 +/- 0.27 m/s, P
      > 0.05, by RASM; 0.75 +/- 0.25 vs 0.92 +/- 0.27 vs 0.82 +/- 0.35 m/s, P > 0.05 by
      SMI), respectively. Multiple linear regression analyses showed that thigh
      skeletal muscle mass was positively correlated with gait speed independently
      (beta = 0.221, P = 0.011), and total body fat (beta = -0.216, P = 0.002) and age
      (beta = -0.524, P = 0.000) were negatively correlated with gait speed
      independently. CONCLUSIONS: The prevalence of sarcopenia is high either based on
      RASM or SMI among Chinese men aged 80 years and older. Functional limitations
      were significantly associated with older age, skeletal muscle mass and total body
      fat.

PMID- 24450559
TI  - Sarcopenia, and its association with cardiometabolic and functional
      characteristics in Taiwan: results from I-Lan Longitudinal Aging Study.
AB  - AIM: Sarcopenia is a well-recognized geriatric syndrome, which is associated with
      a variety of adverse outcomes. The present study aimed to evaluate the prevalence
      of sarcopenia and its associative clinical characteristics in Taiwan. METHODS:
      Data of the I-Lan Longitudinal Aging Study (ILAS) were retrieved for this study.
      Sarcopenia was defined according to the European Working Group on Sarcopenia in
      Older People criteria, and comparisons of demographic characteristics, physical
      performance, body composition, cardiometabolic profiles and functionality
      indicators were carried out. RESULTS: Overall, data of 1008 participants (mean
      age 65.2 +/- 9.3 years, male 50.6%) were retrieved for analysis. The cut-off
      value of relative appendicular skeletal muscle was 7.0 kg/m(2) for men and 5.9
      kg/m(2) for women. Sarcopenia was significantly related to low body mass index,
      smaller waist circumference, poor nutrition and poor cognition. The mean carotid
      intima-media thickness and cardiometabolic parameters showed no statistically
      significant findings. CONCLUSIONS: The present paper showed the epidemiology of
      sarcopenia, and the strong connection to functionality indicators. However,
      sarcopenia was not associated with cardiometabolic risk or carotid intima media
      thickness in the present study.

PMID- 24450560
TI  - Using two different algorithms to determine the prevalence of sarcopenia.
AB  - AIM: Several operative definitions and screening methods for sarcopenia have been
      proposed in previous studies; however, the opinions of researchers still differ.
      We compared the prevalence of sarcopenia using two different algorithms: (i) the
      European working group on sarcopenia in older people (EWGSOP)-suggested algorithm
      using gait speed as the first step; and (ii) the muscle mass and strength
      algorithm. METHODS: A population-based, cross-sectional survey of adults aged
      over 65 years was carried out. Data on a total of 4811 participants were
      available for analysis. Gait speed, grip strength and appendicular skeletal
      muscle mass were assessed to determine sarcopenia. Appendicular skeletal muscle
      mass was estimated from bioimpedance analysis measurements and expressed as
      skeletal muscle mass index. Grip strength and skeletal muscle mass index were
      considered to be low if they fell below the threshold of the lowest 20% of values
      measured in a subset of healthy subjects. We compared the prevalence rates of
      sarcopenia determined by the two algorithms. RESULTS: The prevalence rate of
      sarcopenia in a representative sample of older Japanese adults was 8.2% for men
      and 6.8% for women based on the EWGSOP algorithm. The two algorithms identified
      the same participants as sarcopenic, the only difference being the EWGSOP
      algorithm classified an additional seven participants (0.15%) into sarcopenia
      compared with the muscle mass and strength algorithm. CONCLUSION: It is debatable
      whether inclusion of gait speed is necessary when screening for sarcopenia in
      community-dwelling older adults. Future research should examine the necessity of
      including gait speed in algorithms and the validity of cut-off values.

PMID- 24450561
TI  - Epidemiology of sarcopenia among community-dwelling older adults in Taiwan: a
      pooled analysis for a broader adoption of sarcopenia assessments.
AB  - AIM: To develop cut-off points of muscle mass, gait speed and handgrip strength;
      and to examine the prevalence of sarcopenia, and the relationship between
      sarcopenia stages and functional limitations and disability by using these cut
      off points. METHODS: We pooled individual participant data of 2867 community
      dwelling older adults from five cohort studies. We defined the cut-off point of a
      muscle mass index (ASM/ht(2)) as the values of two standard deviations below the
      sex-specific means of a young population or as the 20th percentile of the sex
      specific distribution in our study population. The gait speed and handgrip
      strength cut-off points were defined as the 20th percentile of their population
      distributions. We also measured functional limitations, using the Short Physical
      Performance Battery, and the number of activities of daily living and
      instrumental activities of daily living difficulties. RESULTS: We identified the
      cut-off points of ASM/ht(2), gait speed and handgrip strength. By applying these
      cut-off points to our study population, the prevalence of sarcopenia varied from
      3.9% (2.5% in women and 5.4% in men) to 7.3% (6.5% in women and 8.2% in men). A
      higher sarcopenia stage was independently associated with a lower summary
      performance score, as well as more activities of daily living and instrumental
      activities of daily living difficulties (P < 0.05 for all). CONCLUSIONS: The
      prevalence of sarcopenia in community-dwelling older adults is comparable with
      those in other populations. A dose-response relationship exists between
      sarcopenia stages and functional limitations/disability. The European Working
      Group on Sarcopenia in Older People consensus definition using these cut-off
      points is suitable for determining sarcopenia cases in the elderly population of
      Taiwan.

PMID- 24450562
TI  - Cut-off points of quadriceps strength, declines and relationships of sarcopenia
      related variables among Thai community-dwelling older adults.
AB  - AIM: To define quadriceps strength cut-off points for both sexes to be used in
      the working diagnosis of sarcopenia in older Asian people, and to investigate the
      age-related declines of sarcopenia-related variables and correlations between
      those variables among community-dwelling older adults. METHODS: The present 3
      year prospective study was a part of the Bangkok Longitudinal Study by Siriraj
      Hospital for Older Men and Women. Data on 2149 participants aged >= 60 years were
      included in this analysis. RESULTS: The quadriceps strength cut-off points,
      identified based on mobility decline over 2 years of follow up, were 18.0 kg for
      men and 16.0 kg for women. When these cut-off points were applied to the whole
      population aged >= 60 years (n = 950), the low quadriceps strength group had
      poorer results on all clinical variables when compared with the normal quadriceps
      strength group. Although nearly all of the sarcopenia-related variables declined
      over 2 years of follow up in both older men and women, more significant
      differences between age groups were seen in older women. Quadriceps strength had
      the highest degree of correlation with total lean body mass in all age groups (r
      = 0.550-0.584, P < 0.001), followed by the 6-min walk test in all age groups (r =
      0.449-0.516, P < 0.001). CONCLUSIONS: The quadriceps strength cut-off points of
      18.0 kg for older men and 16.0 kg for older women would be useful as a muscle
      strength measurement for use in any diagnostic algorithm; for example, sarcopenia
      diagnosis in older Asian people.

PMID- 24450563
TI  - Prevalence and associated factors of sarcopenia and severe sarcopenia in older
      Taiwanese living in rural community: the Tianliao Old People study 04.
AB  - AIM: The aim of the present study was to show the prevalence and associated
      factors of sarcopenia and severe sarcopenia in rural community-dwelling older
      Taiwanese. METHODS: Using the whole community sampling method, a total of 285 men
      and 264 women aged over 65 years were randomly sampled (response rate = 50%) from
      Tianliao District, southern Taiwan, in 2012. Participants were interviewed by
      trained investigators to complete a validated structural questionnaire. Body
      composition was measured by bioelectrical impedance analysis, and skeletal muscle
      mass was estimated by Janssen's equation. The Mini-Nutritional Assessment (MNA)
      score, Short Portable Mental Status Questionnaire, grip strength, gait speed and
      short physical performance battery (SPPB) were obtained by the standard
      procedures. Sarcopenia and severe sarcopenia were defined according to the 2010
      consensus of the Report of the European Working Group on Sarcopenia in Older
      People. RESULTS: Of the 549 study participants, 39 (7.1%) were classified as
      having sarcopenia and 31 (5.6%) participants were classified as having severe
      sarcopenia. Using multiple logistic regression models, the age, sex, working
      status, waist circumference, body mass index, hypertensive history, MNA and SPPB
      score were independently associated with different stages of sarcopenia.
      CONCLUSIONS: Approximately one-fifth of community-dwelling older adults were
      facing the threat of sarcopenia in southern Taiwan. The older age, female sex,
      lower body mass index, higher waist circumference, a history of hypertension,
      lower MNA or SPPB score and not working regularly were associated factors for
      either sarcopenia or severe sarcopenia.

PMID- 24450564
TI  - Age-associated decline of muscle mass, grip strength and gait speed: a 4-year
      longitudinal study of 3018 community-dwelling older Chinese.
AB  - AIMS: Studies about sarcopenia in Asia are fewer, and started later than in
      Europe and America. We attempted to examine the decline in muscle mass, grip
      strength and gait speed in a cohort of older Chinese prospectively over 4 years.
      METHODS: We recruited 4000 community-living Chinese older than 64 years, and
      measured their appendicular skeletal mass (ASM) by dual-energy X-ray
      absorptiometry, grip strength, and gait speed at baseline and after 2 years.
      Muscle mass and gait speed were additionally measured after 4 years. RESULTS:
      After 4 years, 3018 participants completed all the measurements. The annualized
      decline in grip strength (-0.798 kg/year vs -1.239 kg/year) and gait speed (
      0.019 m/s/year vs - 0.025 m/s/year) was faster in women than in men. Muscle mass
      was relatively preserved in comparison with grip strength and gait speed. The
      percentage loss of ASM in 4 years was -1.59% and -2.02% in men and women,
      respectively. The percentage decline in gait speed after 4 years was -8.2% in men
      and -9.0% in women. However, the decline in grip strength was more rapid,
      particularly in women, which was -10.0% in 2 years and less so in men, -3.85% in
      2 years. CONCLUSION: Compared with black people and white people, the older
      Chinese have less muscle mass, weaker grip strength and slower gait speed.
      Although the rate of loss of ASM was modest, the decline in gait speed was rapid
      and the decline in grip strength was particularly fast in older Chinese women.

PMID- 24450565
TI  - Age-related changes in skeletal muscle mass among community-dwelling Japanese: a
      12-year longitudinal study.
AB  - AIM: The present study aimed to evaluate age-related changes in skeletal muscle
      mass among community-dwelling middle-aged and elderly Japanese. METHODS: This 12
      year longitudinal study of a community-dwelling population in Japan included
      15,948 examinations of 1962 men and 1990 women. We assessed appendicular muscle
      mass (AMM) using dual X-ray absorptiometry and calculated the skeletal muscle
      index (SMI) using the AMM divided by height squared (kg/m(2) ). Low muscle mass
      was defined as muscle mass minus two standard deviations below the mean for young
      healthy adults. Leg extension power (watts) was measured as an index of muscle
      function. Longitudinal data of skeletal muscle mass were analyzed using a general
      linear mixed-effect model. RESULTS: The prevalence of low muscle mass at the
      first wave of examinations was 27.1% in men and 16.4% in women. Longitudinal
      analysis showed that skeletal muscle mass decreased with aging during the 12-year
      study period except in middle-aged men, and to a greater extent in elderly men (P
      for trend, <0.001). Skeletal muscle mass decreased slightly, but significantly,
      in women. Although a cross-sectional analysis showed that SMI did not differ with
      age in women, leg extension power per leg muscle mass and grip strength per arm
      muscle mass as indices of muscle quality were significantly lower in older women
      (P for trend, <0.001 for both). CONCLUSION: Age-related decreases in muscle mass
      were trivial, especially in women, but the quality of muscle decreased with aging
      in both sexes.

PMID- 24450566
TI  - Development of a simple screening test for sarcopenia in older adults.
AB  - AIM: To develop a simple screening test to identify older adults at high risk for
      sarcopenia. METHODS: We studied 1971 functionally independent, community-dwelling
      adults aged 65 years or older randomly selected from the resident register of
      Kashiwa city, Chiba, Japan. Data collection was carried out between September and
      November 2012. Sarcopenia was defined based on low muscle mass measured by
      bioimpedance analysis and either low muscle strength characterized by handgrip or
      low physical performance characterized by slow gait speed. RESULTS: The
      prevalence of sarcopenia was 14.2% in men and 22.1% in women. After the variable
      selection procedure, the final model to estimate the probability of sarcopenia
      included three variables: age, grip strength and calf circumference. The area
      under the receiver operating characteristic curve, a measure of discrimination,
      of the final model was 0.939 with 95% confidence interval (CI) of 0.918-0.958 for
      men, and 0.909 with 95% CI of 0.887-0.931 for women. We created a score chart for
      each sex based on the final model. When the sum of sensitivity and specificity
      was maximized, sensitivity, specificity, and positive and negative predictive
      values for sarcopenia were 84.9%, 88.2%, 54.4%, and 97.2% for men, 75.5%, 92.0%,
      72.8%, and 93.0% for women, respectively. CONCLUSIONS: The presence of sarcopenia
      could be detected using three easily obtainable variables with high accuracy. The
      screening test we developed could help identify functionally independent older
      adults with sarcopenia who are good candidates for intervention.

PMID- 24450567
TI  - Association of cognitive impairment, depressive symptoms and sarcopenia among
      healthy older men in the veterans retirement community in southern Taiwan: a
      cross-sectional study.
AB  - AIM: To evaluate the association of cognitive impairment, depressive mood and
      sarcopenia among older men living in the veterans retirement community in
      southern Taiwan METHODS: This cross-sectional study recruited 353 men aged 65
      years and older. In addition to demographic characteristics, all participants
      were measured for gait speed, handgrip strength and muscle mass by using
      bioelectrical impedance analysis (BIA). The diagnosis of sarcopenia was made
      according to the European Working Group on Sarcopenia in Older People criteria.
      Slow walking speed was defined as <= 0.8 meter/second. Low muscle strength was
      defined as the handgrip strength less than 22.5 kg which was adjusted according
      to Taiwanese norms. A height-adjusted muscle mass of 8.87 kg/m2 from a previous
      Taiwanese study was defined as low muscle mass. Cognitive function was evaluated
      by the Mini-Mental State Examination (MMSE), and the Geriatric Depression Scale
      15 (GDS-15) was used for screening of depressive symptoms. RESULTS: Among the 353
      participants (mean age 82.7 +/- 5.3 years), 30.9% (109/353) were classified as
      sarcopenic. Multivariate logistic regression showed that sarcopenia was
      independently associated with cognitive impairment (adjusted OR 3.03, 95% CI 1.63
      5.65, P < 0.001) and depressive symptoms (adjusted OR 2.25, 95% CI 1.03-4.89, P =
      0.04). CONCLUSIONS: Sarcopenia was significantly associated with cognitive
      impairment and depressive symptoms among otherwise healthy older men living in
      the veterans retirement community. Further outcome study is required to explore
      the interrelationship of cognition, depressive symptoms and sarcopenia in older
      adults.

PMID- 24450568
TI  - Arterial stiffness is associated with low skeletal muscle mass in Japanese
      community-dwelling older adults.
AB  - AIM: To examine whether arterial stiffness, measured by the cardio-ankle vascular
      index (CAVI), is associated with skeletal muscle mass index (SMI) in Japanese
      community-dwelling older adults. METHODS: Data were collected from 175
      participants through questionnaires and specific tests; the data included
      demographic, lifestyle and health characteristics, body mass index (BMI), and
      body composition features determined by the bioelectrical impedance analysis,
      ankle-brachial index, the Mini-Nutritional Assessment, handgrip strength (GS),
      walking speed and shuttle walking tests (SW), and arterial stiffness determined
      by the CAVI. Absolute SMI was dichotomized according to the first quintile, which
      determined low (n = 35) and normal (n = 140) SMI. RESULTS: Participants with low
      SMI were older (P = 0.01), had more polypharmacy (P = 0.01), a lower BMI (P <
      0.001), and fat mass index (P = 0.02), and had a greater risk of malnutrition (P
      < 0.001) than the normal group. Additionally, they showed poorer physical
      performance (GS and SW, P = 0.007 and 0.01, respectively) than the normal group.
      Furthermore, CAVI was associated with SMI even after adjustments (OR 1.82, 95% CI
      1.14-2.90, P = 0.01). CONCLUSIONS: Our data showed that arterial stiffness is
      associated with low SMI in community-dwelling older adults, even when adjusting
      by multiple factors, showing a close interaction of vascular aging and muscle
      mass decline.

PMID- 24450569
TI  - Type 2 diabetes is associated with low muscle mass in older adults.
AB  - AIMS: Our aim was to clarify the association between type 2 diabetes and the risk
      of low muscle mass in older adults. METHODS: In the present study, 414 adults
      aged 65 years or older (144 patients with type 2 diabetes and 270 control
      participants) were included. Body composition was measured by dual-energy X-ray
      absorptiometry. Low muscle mass was defined as the appendicular skeletal muscle
      mass/height(2) (ASM/Ht(2)) or appendicular skeletal muscle mass/weight (ASM/Wt)
      of <2 SD below the sex-specific normal mean of the young reference group, or
      <lower 20th percentile of total body skeletal muscle mass/weight (TSM/Wt) from
      control participants. RESULTS: Older men with type 2 diabetes showed
      significantly lower appendicular skeletal muscle mass than those without diabetes
      (19.5 +/- 3.5 kg vs 21.0 +/- 2.8 kg, P < 0.001). The prevalence of low muscle
      mass was consistently higher in older men with diabetes than those without
      diabetes defined by ASM/Ht(2) (57.6% vs 41.5%, P = 0.040), ASM/Wt (23.7% vs
      12.3%, P = 0.046) and TSM/Wt (49.2% vs 20.0%, P < 0.001). In older women with
      diabetes, the prevalence of low muscle mass was higher than those without
      diabetes by ASM/Wt (25.9% vs 15.0%, P = 0.044) and TSM/Wt (32.9% vs 20.0%, P =
      0.030), but not by ASM/Ht(2) (7.1% vs 8.6%, P = 0.685). The risk of low muscle
      mass was approximately two- to fourfold higher in older adults with type 2
      diabetes, even after adjusting for age, body mass index, current smoking and
      other risk factors. CONCLUSIONS: In Korean older adults, type 2 diabetes is
      associated with low muscle mass.

PMID- 24450570
TI  - Use of alfacalcidol in osteoporotic patients with low muscle mass might increase
      muscle mass: an investigation using a patient database.
AB  - AIM: Sarcopenia causes a decline in physical performance and decreased quality of
      life. However, there is little evidence for effective treatments. Because of the
      similarities between osteoporosis and sarcopenia, alfacalcidol used for
      osteoporosis might be beneficial for low muscle mass. Therefore, we investigated
      the effect of alfacalcidol on muscle mass in patients with low muscle mass.
      METHODS: In this retrospective cohort analysis, patients from an osteoporosis
      database were divided into two groups: alfacalcidol-treated patients (vitamin D
      group; n = 156) and a control group without drug treatment (n = 233). Muscle mass
      was evaluated in terms of the skeletal muscle index (SMI; kg/m(2)) obtained from
      dual-energy X-ray absorptiometry measurements that were taken at the start and
      end of a 1-year period. Low muscle mass was determined using specific SMI cut
      offs for Japanese individuals. RESULTS: Both the vitamin D group (mean age 73.7
      +/- 9.8 years) and the control group (mean age 72.3 +/- 11.9 years) were
      primarily women (n = 141, 90.4%; n = 189, 81.1%, respectively). Low muscle mass
      was identified in 32.7% (n = 51) of the vitamin D group and 32.2% (n = 75) of the
      control group. The mean appendicular SMI in the vitamin D group did not change
      significantly over the 1-year period. The change was significant among the
      patients with low muscle mass (5.30 kg/m(2) vs 5.49 kg/m(2)). The mean
      appendicular SMI in the control group decreased significantly over the 1-year
      period (6.09 kg/m(2) vs 5.99 kg/m(2)). The change in the patients with low muscle
      mass was not significant. CONCLUSIONS: The vitamin D group maintained muscle
      mass, and the SMI increased in patients with low muscle mass. Thus, the use of
      alfacalcidol might be effective in osteoporotic patients with low muscle mass.

PMID- 24450571
TI  - Application of segmental bioelectrical impedance spectroscopy to the assessment
      of skeletal muscle cell mass in elderly men.
AB  - AIM: It is important to assess not only the total skeletal muscle mass, but also
      the intracellular and extracellular compartments of skeletal muscle to examine
      the actual relationship between skeletal muscle mass and physical functions.
      Segmental bioelectrical impedance spectroscopy is a unique tool with which to
      assess intracellular and extracellular water in the limbs. The aim of the present
      study was to examine the application of segmental bioelectrical impedance
      spectroscopy to the assessment of skeletal muscle mass in the elderly. METHODS: A
      total of 73 healthy elderly men and 20 elderly men requiring care and using an
      ambulatory day-care service of the public long-term care insurance system
      participated in the present study. The intracellular and extracellular water in
      the upper and lower legs were assessed by segmental bioelectrical impedance
      spectroscopy. The gait speed, grip strength and maximal isometric knee extension
      strength were measured. RESULTS: The elderly requiring care had significantly
      lower intracellular water than did healthy elderly in the upper and lower legs. A
      significant relative expansion of extracellular water against total water was
      observed in the elderly requiring care. Receiver operating characteristic curves
      showed that the area under the curve for the intracellular water index was
      similar to that for muscle strength in the discrimination of elderly requiring
      care. CONCLUSIONS: The elderly requiring care had a relative expansion of
      extracellular water in the legs, which could have masked actual muscle atrophy.
      Segmental bioelectrical impedance spectroscopy would be useful for the assessment
      of skeletal muscle cell mass and sarcopenia in the elderly.

PMID- 24450573
TI  - Trabectedin for advanced soft tissue sarcomas: a single institution experience.
AB  - BACKGROUND: We retrospectively analyzed data from patients who had been treated
      with trabectedin at our institution between April 2009 and August 2011. PATIENTS
      & METHODS: Data from 25 patients with recurrent soft tissue sarcoma
      (leiomyosarcoma: n = 8; liposarcoma: n = 5) were used to assess the efficacy and
      safety of trabectedin 1.5 mg/m(2) given every 3 weeks. RESULTS: Most patients (n
      = 14) had been heavily pretreated with >= 2 previous chemotherapy lines. Eight
      (32%) patients achieved a partial response according to dimensional and tumor
      density changes, and seven (28%) patients had stable disease for >= 3 months
      (clinical benefit rate = 60%; n = 15). Median progression-free survival was 6.4
      months and overall survival 19.3 months. Common adverse events were fatigue,
      nausea, anemia and transient transaminase increases. CONCLUSION: Treatment with
      trabectedin is effective and well tolerated in heavily pretreated soft tissue
      sarcoma patients. Tapering dexamethasone courses and switching trabectedin
      administration to an every 4 weeks schedule effectively dealt with persistent
      fatigue without compromising effectiveness.

PMID- 24450574
TI  - Cancer-related fatigue and chemotherapy-associated adverse effects: correlation
      with TNF-alpha, IL-1 and 17-hydroxycorticosteroids.
AB  - AIM: We sought to determine the relationship between cancer-related fatigue,
      chemotherapy-associated adverse effects in patients with advanced stages of
      cancer, and the levels of TNF-alpha, IL-1 and 17-hydroxycorticosteroids (17-HCS).
      PATIENTS & METHODS: Two hundred cancer patients were recruited. They were given a
      Cancer Fatigue Scale survey to assess their general state of health before and
      after chemotherapy. Their plasma levels of TNF-alpha and IL-1 and urine levels of
      17-HCS were also measured. RESULTS: Increased levels of TNF-alpha and IL-1 are
      common in cancer patients. Thirty-five (17.5%) patients suffered from
      chemotherapy-associated adverse effects, but their plasma levels of TNF-alpha and
      IL-1 were not significantly elevated after chemotherapy. However, the urinary
      levels of 17-HCS levels were significantly elevated in 23 patients after
      chemotherapy. CONCLUSION: Patients who had elevated urinary levels of 17-HCS
      before chemotherapy are accompanied by chemotherapy-associated adverse effects.
      Thus, elevated 17-HCS in urine could be a possible predictor for chemotherapy
      associated adverse effects.

PMID- 24450572
TI  - Unique effect of Cu(II) in the metal-induced amyloid formation of beta-2
      microglobulin.
AB  - beta-2-Microglobulin (beta2m) forms amyloid fibrils in the joints of patients
      undergoing hemodialysis treatment as a result of kidney failure. In the presence
      of stoichiometric amounts of Cu(II), beta2m self-associates into discrete
      oligomeric species, including dimers, tetramers, and hexamers, before ultimately
      forming amyloid fibrils that contain no copper. To improve our understanding of
      whether Cu(II) is unique in its ability to induce beta2m amyloid formation and to
      delineate the coordinative interactions that allow Cu(II) to exert its effect, we
      have examined the binding of Ni(II) and Zn(II) to beta2m and the resulting
      influence that these metals have on beta2m aggregation. We find that, in contrast
      to Cu(II), Ni(II) does not induce the oligomerization or aggregation of beta2m,
      while Zn(II) promotes oligomerization but not amyloid fibril formation. Using X
      ray absorption spectroscopy and new mass spectrometry-related techniques, we find
      that different binding modes are responsible for the different effects of Ni(II)
      and Zn(II). By comparing the binding modes of Cu(II) with Ni(II), we find that
      Cu(II) binding to Asp59 and the backbone amide between the first two residues of
      beta2m are important for allowing the formation of amyloid-competent oligomers,
      as Ni(II) appears not to bind these sites on the protein. The oligomers formed in
      the presence of Zn(II) are permitted by this metal's ability to bridge two beta2m
      units via His51. These oligomers, however, are not able to progress to form
      amyloid fibrils because Zn(II) does not induce the required structural changes
      near the N-terminus and His31. 

PMID- 24450575
TI  - Neutrophil-tumor cell cannibalism in oral squamous cell carcinoma.
AB  - BACKGROUND: Cannibalism was recognized as a phenomenon seen mainly with the tumor
      cells ingesting other tumor cells. Recent reports have shown tumor cell engulfing
      other cells (xeno-cannibalism) as well, such as neutrophils, lymphocytes and
      erythrocytes. But no such finding has been reported in oral squamous cell
      carcinoma (OSCC) in the literature till date. OBJECTIVE: Retrospective
      histopathological analysis of OSCC for identification of neutrophil-tumor cell
      cannibalism (NTCC) and its correlation with clinico-pathological parameters.
      METHODS: The hematoxylin and eosin stained tissue sections of 500 OSCC cases were
      thoroughly screened at high power magnification (400X) for NTCC. Cases showing
      only frank NTCC were selected. Cases were subjected to immunohistochemical
      analysis using CD68 and lysozyme. RESULTS: Seven (1.4%) cases of OSCC which
      showed classical features of extreme NTCC on histopathological examination.
      Seventeen Cases (3.4%) showing occasional isolated NTCC were excluded. All the
      cases were poorly differentiated and showed cervical lymph node metastasis.
      Immunohistochemical analysis showed mild (+) to moderate (++) positivity in tumor
      cells for CD68 and lysozyme markers. CONCLUSION: NTCC in OSCC can predict the
      biological behavior and could serve as a useful prognostic marker in future.
      Tumor cell displaying macrophage phenotype and cell digestion could be mediated
      through lysosomal enzyme activity.

PMID- 24450577
TI  - Gastrointestinal bleeding in hospitalized children in the United States.
AB  - OBJECTIVE: To investigate the epidemiology of GI bleeding in hospitalized
      children in the United States. METHODS: Data were obtained from the Healthcare
      Cost and Utilization Project Kids' Inpatient Database, Agency for Healthcare
      Research and Quality for the year 2009. The data were weighted to generate
      national-level estimates. RESULTS: There were 23,383 pediatric discharges with a
      diagnosis of GI bleeding accounting for 0.5% of all discharges. Children with a
      GI bleed compared to those without were more likely to be male (54.5% vs. 45.8%;
      P < 0.001), older (children >=11 years; 50.8% vs. 38.7%; P < 0.001), and admitted
      to a teaching hospital (70.5% vs. 56.4%; P < 0.001). Children 11-15 years of age
      had the highest incidence of GI bleeding (84.2 per 10,000 discharges) and
      children less than 1 year of age the lowest (24.4 per 10,000 discharges). The
      highest incidence of GI bleeding was attributable to cases coded as blood in
      stool (17.6 per 10,000 discharges) followed by hematemesis (11.2 per 10,000
      discharges). Those with a GI bleed had a higher co-morbid burden (12.3% vs. 2.3%;
      P < 0.001) and severity of illness (40.1% vs. 14.5%; P < 0.001). The highest
      mortality rates associated with GI bleeding were observed in cases with
      intestinal perforation (8.7%) and esophageal perforation (8.4%). GI bleeding was
      independently associated with a higher risk of mortality (aOR 1.68, CI 1.53
      1.84). CONCLUSIONS: Our results describe the epidemiology of GI bleeding in
      hospitalized children within the United States. We found a substantial risk of
      mortality attributable to GI bleeding in this patient population. Our study is
      limited by the exclusion of non-hospitalized children, the reliance on ICD-9-CM
      codes and the absence of longitudinal follow up of patients.

PMID- 24450576
TI  - Early microbial and metabolomic signatures predict later onset of necrotizing
      enterocolitis in preterm infants.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating intestinal disease
      that afflicts 10% of extremely preterm infants. The contribution of early
      intestinal colonization to NEC onset is not understood, and predictive biomarkers
      to guide prevention are lacking. We analyzed banked stool and urine samples
      collected prior to disease onset from infants <29 weeks gestational age,
      including 11 infants who developed NEC and 21 matched controls who survived free
      of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing.
      Urinary metabolomic profiles were assessed by NMR. RESULTS: During postnatal days
      4 to 9, samples from infants who later developed NEC tended towards lower alpha
      diversity (Chao1 index, P = 0.086) and lacked Propionibacterium (P = 0.009)
      compared to controls. Furthermore, NEC was preceded by distinct forms of
      dysbiosis. During days 4 to 9, samples from four NEC cases were dominated by
      members of the Firmicutes (median relative abundance >99% versus <17% in the
      remaining NEC and controls, P < 0.001). During postnatal days 10 to 16, samples
      from the remaining NEC cases were dominated by Proteobacteria, specifically
      Enterobacteriaceae (median relative abundance >99% versus 38% in the other NEC
      cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis
      occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria
      dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were
      preceded by either Firmicutes (>=98% relative abundance, days 4 to 9) or
      Proteobacteria (>=90% relative abundance, days 10 to 16) dysbiosis, while only
      25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of
      days 4 to 9 urine samples found no metabolites associated with all NEC cases, but
      alanine was positively associated with NEC cases that were preceded by Firmicutes
      dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases
      preceded by Proteobacteria dysbiosis (P = 0.013). A high urinary
      alanine:histidine ratio was associated with microbial characteristics (P < 0.001)
      and provided good prediction of overall NEC (predictive value 78%, P = 0.007).
      CONCLUSIONS: Early dysbiosis is strongly involved in the pathobiology of NEC.
      These striking findings require validation in larger studies but indicate that
      early microbial and metabolomic signatures may provide highly predictive
      biomarkers of NEC.

PMID- 24450578
TI  - Protein immobilization in hollow nanostructures and investigation of the adsorbed
      protein behavior.
AB  - Understanding nanomaterial-biomolecule interactions is critical to develop broad
      applications in sensors, devices, and therapeutics. During the past decade, in
      depth studies have been performed on the effect of nanoscale surface topography
      on adsorbed protein structure and function. However, a fundamental understanding
      of nanobio interactions at concave surfaces is limited; the greatest challenge is
      to create a nanostructure that allows such interactions to occur and to be
      characterized. We have synthesized hollow nanocages (AuNG) through careful
      control of morphology and surface chemistry. Lysozyme was used as a model to
      probe interactions between a protein and these nanostructures. Solid Au
      nanoparticles with a similar morphology and surface chemistry were also used as a
      reference. Through a series of quantitative analyses of protein adsorption
      profiles and enzymatic activity assays of both nanobioconjugates, we discovered
      that a significant amount of protein could be delivered into the core of AuNG,
      while maintaining a substantial fraction of native activity. 

PMID- 24450579
TI  - Health resource utilization and cost associated with myeloproliferative neoplasms
      in a large United States health plan.
AB  - Myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET) may
      lead to bone marrow fibrosis. Because the disease course of ET and PV are long
      and the disease course of MF may be fatal, healthcare resource utilization (HRU)
      associated costs of these neoplasms are especially important to understand. We
      used a large US health insurance claim database to describe the costs of these
      diseases. Compared to age-gender matched comparisons without myeloproliferative
      neoplasms (MPN), all aspects of HRU that we examined, including inpatient,
      outpatient and emergency room visits and pharmacy, as well as overall healthcare
      expenditures, were significantly higher in patients with MF, PV and ET (e.g. MF
      total costs = $54 168 vs. $10 203; PV = $14 903 vs. $7913; ET = $29 553 vs.
      $8026) than in matched comparisons. In order to reduce the burden of illness
      associated with these diseases, continued efforts in the development of more
      efficacious treatments for these disorders are needed.

PMID- 24450580
TI  - Chemoimmunotherapy resistant follicular lymphoma: predictors of resistance,
      association with transformation and prognosis.
AB  - Follicular lymphoma (FL) is characterized by an initial response to treatment
      with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR
      resistance) including transformation. We identified patients who received
      rituximab combination therapy for symptomatic FL. CIR resistance was defined as
      disease progression during rituximab-based chemoimmunotherapy, rituximab
      maintenance or within 6 months of treatment completion. Our primary outcome was
      time to early progression (CIR resistance). Between July 2006 and April 2010, 132
      patients met the inclusion criteria and 22 (16.7%) demonstrated CIR resistance
      with a median follow-up of 33 months. High-risk Follicular Lymphoma International
      Prognostic Index (FLIPI) score was predictive of CIR resistance (hazard ratio
      [HR] 2.43; 95% confidence interval [CI], 1.4-4.1; p = 0.001). Overall, eight
      patients (36.3%) transformed (biopsy-proven), with no transformation in the
      chemoimmunotherapy responder group. Median overall survival in the CIR resistant
      group was 47 months. Patients with CIR resistance had high rates of histologic
      transformation and shorter survival with poor response to next therapy.

PMID- 24450581
TI  - Deletion in the gene BruAb2_0168 of Brucella abortus strains: diagnostic
      challenges.
AB  - Three Brucella abortus strains were isolated from joint hygromas from cows in
      northern Togo. Two deletions in the 5' side of the gene BruAb2_0168 were
      identified. As this gene is used for species identification, these deletions have
      consequences for diagnostic procedures. Multiple locus variable number of tandem
      repeat (VNTR) analysis was therefore performed for species identification. The
      strains showed unique VNTR profiles, providing some of the first genotypic data
      from West Africa. More molecular and epidemiological data are needed from the
      region, in order to better understand transmission patterns and develop suitable
      diagnostic assays. 

PMID- 24450582
TI  - Neural correlates of experienced moral emotion: an fMRI investigation of emotion
      in response to prejudice feedback.
AB  - Guilt, shame, and embarrassment are quintessential moral emotions with important
      regulatory functions for the individual and society. Moral emotions are, however,
      difficult to study with neuroimaging methods because their elicitation is more
      intricate than that of basic emotions. Here, using functional MRI (fMRI), we
      employed a novel social prejudice paradigm to examine specific brain regions
      associated with real-time moral emotion, focusing on guilt and related moral
      negative emotions. The paradigm induced intense moral-negative emotion (primarily
      guilt) in 22 low-prejudice individuals through preprogrammed feedback indicating
      implicit prejudice against Black and disabled people. fMRI data indicated that
      this experience of moral-negative emotion was associated with increased activity
      in anterior paralimbic structures, including the anterior cingulate cortex (ACC)
      and anterior insula, in addition to areas associated with mentalizing, including
      the dorsomedial prefrontal cortex, posterior cingulate cortex, and precuneus. Of
      significance was prominent conflict-related activity in the supragenual ACC,
      which is consistent with theories proposing an association between acute guilt
      and behavioral inhibition. Finally, a significant negative association between
      self-reported guilt and neural activity in the pregenual ACC suggested a role of
      self-regulatory processes in response to moral-negative affect. These findings
      are consistent with the multifaceted self-regulatory functions of moral-negative
      emotions in social behavior. 

PMID- 24450583
TI  - Aspen pectate lyase PtxtPL1-27 mobilizes matrix polysaccharides from woody
      tissues and improves saccharification yield.
AB  - BACKGROUND: Wood cell walls are rich in cellulose, hemicellulose and lignin.
      Hence, they are important sources of renewable biomass for producing energy and
      green chemicals. However, extracting desired constituents from wood efficiently
      poses significant challenges because these polymers are highly cross-linked in
      cell walls and are not easily accessible to enzymes and chemicals. RESULTS: We
      show that aspen pectate lyase PL1-27, which degrades homogalacturonan and is
      expressed at the onset of secondary wall formation, can increase the solubility
      of wood matrix polysaccharides. Overexpression of this enzyme in aspen increased
      solubility of not only pectins but also xylans and other hemicelluloses,
      indicating that homogalacturonan limits the solubility of major wood cell wall
      components. Enzymatic saccharification of wood obtained from PL1-27
      overexpressing trees gave higher yields of pentoses and hexoses than similar
      treatment of wood from wild-type trees, even after acid pretreatment.
      CONCLUSIONS: Thus, the modification of pectins may constitute an important
      biotechnological target for improved wood processing despite their low abundance
      in woody biomass.

PMID- 24450585
TI  - Experimental and modeling study of the thermal decomposition of C3-C5 ethyl
      esters behind reflected shock waves.
AB  - The thermal decomposition of three ethyl esters, ethyl formate (C3H6O2), ethyl
      acetate (C4H8O2), and ethyl propanoate (C5H10O2), was studied behind reflected
      shock waves using laser absorption to measure concentration time-histories of
      H2O, CO2, and CO. Experimental conditions covered temperatures of 1301-1636 K,
      pressures of 1.48-1.72 atm, and reactant concentrations of 2000 ppm in argon.
      Recently developed mid-infrared laser diagnostics for H2O (2.5 MUm), CO2 (4.3
      MUm), and CO (4.6 MUm) provide orders-of-magnitude greater detectivity compared
      to previous near-infrared absorption sensors. The experimental results have
      highlighted significant differences among these three ethyl esters: negligible
      CO2 production during ethyl formate pyrolysis, quite slow CO formation rate
      during ethyl acetate pyrolysis, and nearly equal formation rate of H2O, CO2, and
      CO during ethyl propanoate pyrolysis. Detailed kinetic modeling was performed to
      understand the destruction pathways of these three ethyl esters with different
      alkyl chain lengths. Rate of production and sensitivity analyses were also
      carried out to interpret the experimental results and to identify the key
      reactions affecting experimental results. 

PMID- 24450584
TI  - Nuclear localization of vascular endothelial growth factor-D and regulation of c
      Myc-dependent transcripts in human lung fibroblasts.
AB  - Lymphangiogenesis and angiogenesis are processes that are, in part, regulated by
      vascular endothelial growth factor (VEGF)-D. The formation of lymphatic
      structures has been implicated in multiple lung diseases, including pulmonary
      fibrosis. VEGF-D is a secreted protein produced by fibroblasts and macrophages,
      which induces lymphangiogenesis by signaling via VEGF receptor-3, and
      angiogenesis through VEGF receptor-2. VEGF-D contains a central VEGF homology
      domain, which is the biologically active domain, with flanking N- and C-terminal
      propeptides. Full-length VEGF-D (~ 50 kD) is proteolytically processed in the
      extracellular space, to generate VEGF homology domain that contains the VEGF-D
      receptor-binding sites. Here, we report that, independent of its cell surface
      receptors, full-length VEGF-D accumulated in nuclei of fibroblasts, and that this
      process appears to increase with cell density. In nuclei, full-length VEGF-D
      associated with RNA polymerase II and c-Myc. In cells depleted of VEGF-D, the
      transcriptionally regulated genes appear to be modulated by c-Myc. These findings
      have potential clinical implications, as VEGF-D was found in fibroblast nuclei in
      idiopathic pulmonary fibrosis, a disease characterized by fibroblast
      proliferation. These findings are consistent with actions of full-length VEGF-D
      in cellular homeostasis in health and disease, independent of its receptors. 

PMID- 24450586
TI  - Interferon gene expression in sputum cells correlates with the Asthma Index Score
      during virus-induced exacerbations.
AB  - BACKGROUND: The majority of asthma exacerbations are related to viral respiratory
      infections. Some, but not all, previous studies have reported that low interferon
      responses in patients with asthma increase the risk for virus-induced
      exacerbations. OBJECTIVE: We sought to determine the relationship between lower
      airway inflammatory biomarkers, specifically interferon gene expression, and the
      severity or presence of an exacerbation in asthmatics experiencing a naturally
      occurring viral infection. METHODS: Sputum samples were analysed from subjects in
      an asthma exacerbation study who experienced a confirmed viral infection.
      Subjects were monitored for daily symptoms, medication use and peak expiratory
      flow rate until baseline. Sputum samples were assessed for cell counts and gene
      expression. RESULTS: Interferon gamma expression was significantly greater in
      patients with asthma exacerbations compared to non-exacerbating patients (P =
      0.002). IFN-alpha1, IFN-beta1 and IFN-gamma mRNA levels correlated with the peak
      Asthma Index (r = 0.58, P < 0.001; r = 0.57, P = 0.001; and r = 0.51, P = 0.004,
      respectively). Additionally, IL-13, IL-10 and eosinophil major basic protein mRNA
      levels were greater in patients with asthma exacerbations compared to non
      exacerbating patients (P = 0.03, P = 0.06 and P = 0.02, respectively), and IL-13
      mRNA correlated with the peak Asthma Index (P = 0.006). CONCLUSIONS: Our findings
      indicate that asthma exacerbations are associated with increased rather than
      decreased expression of interferons early in the course of infection. These
      findings raise the possibility that excessive virus-induced interferon production
      during acute infections can contribute to airway inflammation and exacerbations
      of asthma.

PMID- 24450587
TI  - Dysregulation of the proteasome increases the toxicity of ALS-linked mutant SOD1.
AB  - A hallmark of protein conformational disease, exemplified by neurodegenerative
      disorders, is the expression of misfolded and aggregated proteins. The
      relationship between protein aggregation and cellular toxicity is complex, and
      various models of experimental pathophysiology have often yielded conflicting or
      controversial results. In this study, we examined the biophysical properties of
      amyotrophic lateral sclerosis (ALS)-linked mutations of Cu/Zn superoxide
      dismutase 1 (SOD1) expressed in human tissue culture cells. Fluorescence
      correlation spectroscopy (FCS) and Forster resonance energy transfer (FRET)
      analyses revealed that changes in proteasome activity affected both the
      expression of FCS- and FRET-detected oligomers and cellular toxicity. Under
      normal conditions, highly aggregation-prone mutant SOD1 exhibited very little
      toxicity. However, when the activity of the proteasome was transiently inhibited,
      only upon recovery did we observe the appearance of ordered soluble oligomers,
      which were closely correlated with cellular toxicity. These results shed light on
      the importance of balance in proteostasis and suggest that transient shifts of
      activity in the cellular machinery can alter the course of protein conformational
      transitions and dysregulate modulation of proteasome activity. In
      neurodegenerative disorders including ALS, such changes may be a risk factor for
      pathogenesis. 

PMID- 24450590
TI  - Patents and Heart Valve Surgery - III: Percutaneous Heart Valves.
AB  - Advancements in technology for the treatment of valvularcardiac diseases seek to
      provide solutions for high risk patients in the form of percutaneous valve
      insertion for patients with complicated valvular disease not amenable to more
      traditional options. Within the last decade, cardiac valves designed for
      percutaneous insertion have emerged rapidly as a treatment option for valvular
      disease. This procedure serves as an alternative to open heart surgery, which is
      more invasive and requires longer ICU stay. Thus, the percutaneous valve
      insertion procedure has been used on older, frailer patients who are poor
      candidates for open heart surgery. Designs for percutaneous valve insertion
      systems have been in development for decades, but have only recently been
      approved by the FDA for use. Important considerations include stent design, valve
      design, balloon catheter design, and deployment method.

PMID- 24450589
TI  - Encoded library technology as a source of hits for the discovery and lead
      optimization of a potent and selective class of bactericidal direct inhibitors of
      Mycobacterium tuberculosis InhA.
AB  - Tuberculosis (TB) is one of the world's oldest and deadliest diseases, killing a
      person every 20 s. InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis,
      is the target of the frontline antitubercular drug isoniazid (INH). Compounds
      that directly target InhA and do not require activation by mycobacterial catalase
      peroxidase KatG are promising candidates for treating infections caused by INH
      resistant strains. The application of the encoded library technology (ELT) to the
      discovery of direct InhA inhibitors yielded compound 7 endowed with good
      enzymatic potency but with low antitubercular potency. This work reports the hit
      identification, the selected strategy for potency optimization, the structure
      activity relationships of a hundred analogues synthesized, and the results of the
      in vivo efficacy studies performed with the lead compound 65. 

PMID- 24450588
TI  - Polygenic risk scores for smoking: predictors for alcohol and cannabis use?
AB  - BACKGROUND AND AIMS: A strong correlation exists between smoking and the use of
      alcohol and cannabis. This paper uses polygenic risk scores to explore the
      possibility of overlapping genetic factors. Those scores reflect a combined
      effect of selected risk alleles for smoking. METHODS: Summary-level P-values were
      available for smoking initiation, age at onset of smoking, cigarettes per day and
      smoking cessation from the Tobacco and Genetics Consortium (n between 22,000 and
      70,000 subjects). Using different P-value thresholds (0.1, 0.2 and 0.5) from the
      meta-analysis, sets of 'risk alleles' were defined and used to generate a
      polygenic risk score (weighted sum of the alleles) for each subject in an
      independent target sample from the Netherlands Twin Register (n = 1583). The
      association between polygenic smoking scores and alcohol/cannabis use was
      investigated with regression analysis. RESULTS: The polygenic scores for
      'cigarettes per day' were associated significantly with the number of glasses
      alcohol per week (P = 0.005, R2 = 0.4-0.5%) and cannabis initiation (P = 0.004,
      R2 = 0.6-0.9%). The polygenic scores for 'age at onset of smoking' were
      associated significantly with 'age at regular drinking' (P = 0.001, R2 = 1.1
      1.5%), while the scores for 'smoking initiation' and 'smoking cessation' did not
      significantly predict alcohol or cannabis use. CONCLUSIONS: Smoking, alcohol and
      cannabis use are influenced by aggregated genetic risk factors shared between
      these substances. The many common genetic variants each have a very small
      individual effect size.

PMID- 24450591
TI  - Budget constraint and vaccine dosing: a mathematical modelling exercise.
AB  - BACKGROUND: Increasing the number of vaccine doses may potentially improve
      overall efficacy. Decision-makers need information about choosing the most
      efficient dose schedule to maximise the total health gain of a population when
      operating under a constrained budget. The objective of this study is to identify
      the most efficient vaccine dosing schedule within a fixed vaccination budget from
      a healthcare payer perspective. METHODS: An optimisation model is developed in
      which maximizing the disease reduction is the functional objective and the
      constraint is the vaccination budget. The model allows variation in vaccination
      dosing numbers, in cost difference per dose, in vaccine coverage rate, and in
      vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an
      example. RESULTS: With a fixed budget, a 2-dose schedule for vaccination against
      rotavirus infection with the monovalent vaccine results in a larger reduction in
      disease episodes than a 3-dose scheme with the same vaccine under most
      circumstances. A 3-dose schedule would only be better under certain conditions: a
      cost reduction of >26% per dose, combined with vaccine efficacy improvement of
      >=5% and a target coverage rate of 75%. Substantial interaction is observed
      between cost reduction per dose, vaccine coverage rate, and increased vaccine
      efficacy. Sensitivity analysis shows that the conditions required for a 3-dose
      strategy to be better than a 2-dose strategy may seldom occur when the budget is
      fixed. The model does not consider vaccine herd effect, precise timing for
      additional doses, or the effect of natural immunity development. CONCLUSIONS:
      Under budget constraint, optimisation modelling is a helpful tool for a decision
      maker selecting the most efficient vaccination dosing schedule. The low dosing
      scheme could be the optimal option to consider under the many scenarios tested.
      The model can be applied under many different circumstances of changing dosing
      schemes with single or multiple vaccines.

PMID- 24450594
TI  - Flavonoids from the pericarps of Litchi chinensis.
AB  - A new methylene-linked flavan-3-ol dimer, bis(8-epicatechinyl)methane (1), was
      isolated from the pericarps of Litchi chinensis Sonn. (Sapindaceae), together
      with dehydrodiepicatechin A (2), proanthocyanidin A1 (3), proanthocyanidin A2
      (4), (-)-epicatechin (5), 8-(2-pyrrolidinone-5-yl)-(-)-epicatechin (6), (-)
      epicatechin 8-C-beta-D-glucopyranoside (7), naringenin 7-O-(2,6-di-O-alpha-L
      rhamnopyranosyl)-beta-D-glucopyranoside (8), and rutin (9). It was the first
      report of compound 2 as a natural product and compounds 6-8 from this species.
      Compounds 1, 2, and 6-8 were evaluated for antioxidant activity. The ferric
      reducing antioxidant powers (FRAP) of compounds 1 and 6 were comparable to that
      of L-ascorbic acid, and the scavenging activities of compounds 1, 2, 6, and 7
      toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azinobis(3
      ethylbenzthiazoline-6-sulfonic acid) radical cations were more potent than those
      of L-ascorbic acid; compound 8 was weak in FRAP and DPPH assays.

PMID- 24450597
TI  - Overexpression of OsKTN80a, a katanin P80 ortholog, caused the repressed cell
      elongation and stalled cell division mediated by microtubule apparatus defects in
      primary root in Oryza sativa.
AB  - Katanin, a microtubule-severing enzyme, consists of two subunits: the catalytic
      subunit P60, and the regulatory subunit P80. In several species, P80 functions in
      meiotic spindle organization, the flagella biogenesis, the neuronal development,
      and the male gamete production. However, the P80 function in higher plants
      remains elusive. In this study, we found that there are three katanin P80
      orthologs (OsKTN80a, OsKTN80b, and OsKTN80c) in Oryza sativa L. Overexpression of
      OsKTN80a caused the retarded root growth of rice seedlings. Further investigation
      indicates that the retained root growth was caused by the repressed cell
      elongation in the elongation zone and the stalled cytokinesis in the division
      zone in the root tip. The in vivo examination suggests that OsKTN80a acts as a
      microtubule stabilizer. We prove that OsKTN80a, possibly associated with OsKTN60,
      is involved in root growth via regulating the cell elongation and division. 

PMID- 24450598
TI  - Stable carbon isotopes in dissolved inorganic carbon: extraction and implications
      for quantifying the contributions from silicate and carbonate weathering in the
      Krishna River system during peak discharge.
AB  - We present a comparative study of two offline methods, a newly developed method
      and an existing one, for the measurement of the stable carbon isotopic
      composition (delta(13)C) of dissolved inorganic carbon (DIC; delta(13)CDIC) in
      natural waters. The measured delta(13)CDIC values of different water samples,
      prepared from laboratory Na2CO3, ground and oceanic waters, and a laboratory
      carbonate isotope standard, are found to be accurate and reproducible to within
      0.5 0/00? (1sigma). The extraction of CO2 from water samples by these methods
      does not require pre-treatment or sample poisoning and can be applied to a
      variety of natural waters to address carbon cycling in the hydrosphere. In
      addition, we present a simple method (based on a two-end-member mixing model) to
      estimate the silicate-weathering contribution to DIC in a river system by using
      the concentration of DIC and its delta(13)C. This approach is tested with data
      from the Krishna River system as a case study, thereby quantifying the
      contribution of silicate and carbonate weathering to DIC, particularly during
      peak discharge.

PMID- 24450599
TI  - Effect of basic cell-penetrating peptides on the structural, thermodynamic, and
      hydrodynamic properties of a novel drug delivery vector, ELP[V5G3A2-150].
AB  - Elastin-like polypeptides (ELPs) are large, nonpolar polypeptides under
      investigation as components of a novel drug delivery system. ELPs are soluble at
      low temperatures, but they desolvate and aggregate above a transition temperature
      (TT). This aggregation is being utilized for targeting systemically delivered ELP
      drug conjugates to heated tumors. We previously examined the structural,
      thermodynamic, and hydrodynamic properties of ELP[V5G3A2-150] to understand its
      behavior as a therapeutic agent. In this study, we investigate the effect that
      adding basic cell-penetrating peptides (CPPs) to ELP[V5G3A2-150] has on the
      polypeptide's solubility, structure, and aggregation properties. CPPs are known
      to enhance the uptake of ELP into cultured cells in vitro and into tumor tissue
      in vivo. Interestingly, the asymmetric addition of basic residues decreased the
      solubility of ELP[V5G3A2-150], although below the TT we still observed a low
      level of self-association that increased with temperature. The DeltaH of the
      aggregation process correlates with solubility, suggesting that the basic CPPs
      stabilize the aggregated state. This is potentially beneficial as the decreased
      solubility will increase the fraction aggregated and enhance drug delivery
      efficacy at a heated tumor. Otherwise, the basic CPPs did not significantly alter
      the biophysical properties of ELP. All constructs were monomeric at low
      temperatures but self-associate with increasing temperature through an indefinite
      isodesmic association. This self-association was coupled to a structural
      transition to type II beta-turns. All constructs reversibly aggregated in an
      endothermic reaction, consistent with a reaction driven by the release of water. 

PMID- 24450600
TI  - Steps towards the discovery of Mycobacterium tuberculosis by Robert Koch, 1882.
AB  - Palaeomicrobiology has detected the tuberculosis agent in animal and human
      skeletons that are thousands of years old. The German doctor Robert Koch was the
      first microbiologist to report in 1882 the successful isolation of the causative
      agent of tuberculosis, named 1 year later as Mycobacterium tuberculosis. This
      immense discovery, however, was not made from scratch, but involved the combining
      of previous scientific knowledge, chiefly the previous demonstration by the
      French doctor Jean-Antoine Villemin that tuberculosis was a transmissible
      disease, and two innovations--a new staining procedure that allowed R. Koch to
      consistently observe the new organism in tuberculous lesions, and use of a
      solidified, serum-based medium instead of broths for the culture. These
      innovations allowed R. Koch not only to isolate M. tuberculosis from animal and
      patient specimens for the first time, but also to reproduce the disease in
      experimentally inoculated guinea pigs. It is thanks to R. Koch that one of the
      most lethal diseases in human history could be diagnosed, could be treated and
      cured after the discovery of streptomycin 65 years later, and could be
      efficiently prevented by isolation of cases. His microbiological innovations are
      now being renewed with molecular and improved culture-based detection being the
      twenty-first century weapons in the fight against this disease, which remains a
      major killer.

PMID- 24450601
TI  - Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and
      their association with disease progression and prognosis.
AB  - BACKGROUND: Recently, studies indicated that cancer stem cell plays a key role in
      cancer development and progression. However, the role of cancer stem cell has not
      been well elucidated in tongue squamous cell carcinoma (TSCC). The objective of
      this study was to investigate the relationships between the expressions of stem
      cell markers and the prognosis of TSCC. MATERIALS AND METHODS:
      Immunohistochemistry was employed to analyse the protein expression levels of
      ALDH1, CD44, OCT4 and SOX2 in 66 TSCC tissue samples. The results were then
      evaluated semiquantitatively and compared with other clinicopathological
      variables. RESULTS: Immunohistochemistry revealed that the ALDH1, CD44, OCT4 and
      SOX2 proteins were overexpressed in the 66 TSCC specimens used in this study.
      Spearman's correlation analysis showed that the expressions of ALDH1 and CD44
      were significantly correlated with SOX2 except other proteins (P < 0.05) and that
      OCT4 and SOX2 were significantly related (P < 0.01). Kaplan-Meier analysis
      revealed that T category, node metastasis, TNM stage, differentiation and distant
      metastasis were associated with poor patient survival (P < 0.05). Multivariate
      Cox regression analysis demonstrated that SOX2, recurrence and distant metastasis
      were independent prognostic factors of overall survival in patients with TSCC.
      CONCLUSION: Taken together, these data suggest that the stem cell markers ALDH1,
      CD44, OCT4 and SOX2 are closely related in TSCC, and the expression of SOX2 can
      be used as a prognostic indicator of TSCC.

PMID- 24450602
TI  - A new system for studying spatial front instabilities: the supercatalytic
      chlorite-trithionate reaction.
AB  - We show that the chlorite-trithionate reaction is "supercatalytic"; i.e., the
      formal kinetic order of the autocatalyst H(+) is 2. A simple model is proposed
      and discussed to describe the unusual concentration dependencies of one
      dimensional front propagation found experimentally. It is also demonstrated that
      at relatively wide concentration ranges the linear two-dimensional front
      initiated loses its stability, giving rise to an appearance of cellular
      structures in a convection-free system. Compared to the chlorite-tetrathionate
      reaction, however, this system is much more stable at alkaline conditions, even
      for hours; therefore, no side reactions can be taken into consideration to check
      whether they may have any side effects on the evolution of spatiotemporal
      structures. 

PMID- 24450603
TI  - Fourier transform infrared spectroscopy as a method to study lipid accumulation
      in oleaginous yeasts.
AB  - BACKGROUND: Oleaginous microorganisms, such as different yeast and algal species,
      can represent a sustainable alternative to plant oil for the production of
      biodiesel. They can accumulate fatty acids (FA) up to 70% of their dry weight
      with a predominance of (mono)unsaturated species, similarly to what plants do,
      but differently from animals. In addition, their growth is not in competition
      either with food, feed crops, or with agricultural land.Despite these advantages,
      the exploitation of the single cell oil system is still at an early developmental
      stage. Cultivation mode and conditions, as well as lipid extraction technologies,
      represent the main limitations. The monitoring of lipid accumulation in
      oleaginous microorganisms is consequently crucial to develop and validate new
      approaches, but at present the majority of the available techniques is time
      consuming, invasive and, when relying on lipid extraction, can be affected by FA
      degradation. RESULTS: In this work the fatty acid accumulation of the oleaginous
      yeasts Cryptococcus curvatus and Rhodosporidium toruloides and of the non
      oleaginous yeast Saccharomyces cerevisiae (as a negative control) was monitored
      in situ by Fourier Transform Infrared Spectroscopy (FTIR). Indeed, this
      spectroscopic tool can provide complementary information to those obtained by
      classical techniques, such as microscopy, flow cytometry and gas chromatography.
      As shown in this work, through the analysis of the absorption spectra of intact
      oleaginous microorganisms it is possible not only to monitor the progression of
      FA accumulation but also to identify the most represented classes of the produced
      lipids. CONCLUSIONS: Here we propose FTIR microspectroscopy - supported by
      multivariate analysis - as a fast, reliable and non invasive method to monitor
      and analyze FA accumulation in intact oleaginous yeasts. The results obtained by
      the FTIR approach were in agreement with those obtained by the other classical
      methods like flow cytometry and gas chromatography. Moreover, the possibility to
      track lipid production in real time is highly desirable to support the initial
      screening of strains and media as well as to optimize the scaling up experiments,
      which are essential for a viable and successful development of an industrial
      production process.

PMID- 24450604
TI  - Development of an equation for estimating appendicular skeletal muscle mass in
      Japanese older adults using bioelectrical impedance analysis.
AB  - AIM: Bioelectrical impedance analysis has been reported to have high reliability
      and accuracy in assessing body composition. However, equations for estimating
      appendicular skeletal muscle mass are population-specific, and few have been
      developed for older Japanese adults. Thus, the purpose of the present study was
      to develop and validate an estimate equation for appendicular skeletal muscle
      mass using bioelectrical impedance analysis. METHODS: A total of 250 older adults
      aged 65 years and older participated in this study. Appendicular skeletal muscle
      mass was measured using dual-energy X-ray absorptiometry, and bioelectrical
      resistance was measured using a multifrequency bioelectrical impedance analyzer.
      Multiple regression analysis was applied to derive sex-specific estimation
      formulae using bioelectrical impedance analysis, and a Bland-Altman analysis was
      used to test agreement. RESULTS: The cross-validation results showed that the
      slopes and intercepts of the regression lines were approximately one and zero,
      respectively, and the coefficients of determination and standard errors of the
      estimate of the newly developed equations were similar between the two groups.
      Thus, the single sex-specific equations were developed using all participants as
      follows. Men: appendicular skeletal muscle mass=0.197 * (impedance index) +0.179
      * (weight) -0.019 (R(2)  =0.87, standard error of the estimate=0.98 kg). Women:
      appendicular skeletal muscle mass=0.221 * (impedance index) +0.117 * (weight)
      +0.881 (R(2)  =0.89, standard error of the estimate=0.81 kg). CONCLUSION: These
      new equations offer a valid option for assessing appendicular skeletal muscle
      mass in older Japanese adults.

PMID- 24450605
TI  - Histamine enhances keratinocyte-mediated resolution of inflammation by promoting
      wound healing and response to infection.
AB  - BACKGROUND: The role of the epidermis in the immune response is well known. While
      multiple cytokines are implicated in keratinocyte-mediated infection clearance
      and wound healing, little is known about the involvement of keratinocytes in
      promoting resolution of inflammation. AIM: To assess effects of histamine
      stimulation on keratinocyte function. METHODS: We performed a combined
      microarray/Gene Ontology analysis of histamine-stimulated keratinocytes.
      Functional changes were tested by apoptosis assessment and scratch assays.
      Histamine receptor involvement was also assessed by blocking wound closure with
      specific antagonists. RESULTS: Histamine treatment had extensive effects on
      keratinocytes, including effects on proinflammatory responses and cellular
      functions promoting wound healing. At the functional level, there was reduced
      apoptosis and enhancement of wound healing in vitro. At the receptor level, we
      identified involvement of all keratinocyte-expressed histamine receptors (HRHs),
      with HRH1 blockage resulting in the most prominent effect. CONCLUSIONS: Histamine
      activates wound healing and infection clearance-related functions of
      keratinocytes. While enhancement of histamine-mediated wound healing is mediated
      predominantly via the HRH1 receptor, other keratinocyte-expressed receptors are
      also involved. These effects could promote resolution of skin inflammation caused
      by infection or superficial injury.

PMID- 24450607
TI  - Intramuscular degloving injuries to the rectus femoris: findings at MRI.
AB  - OBJECTIVE: The purpose of this study was to describe the MRI characteristics of
      intramuscular degloving injuries to the rectus femoris whereby the inner
      bipennate component of the indirect head is dissociated from its superficial
      unipennate component. CONCLUSION: Injuries to the rectus femoris muscle are
      common in athletes, especially European football (soccer) players. The complex
      muscle-within-a-muscle anatomic configuration of the rectus femoris makes it
      susceptible to various types of injuries.

PMID- 24450606
TI  - Female partner preferences enhance offspring ability to survive an infection.
AB  - BACKGROUND: It is often suggested that mate choice enhances offspring immune
      resistance to infectious diseases. To test this hypothesis, we conducted a study
      with wild-derived house mice (Mus musculus musculus) in which females were
      experimentally mated either with their preferred or non-preferred male, and their
      offspring were infected with a mouse pathogen, Salmonella enterica (serovar
      Typhimurium). RESULTS: We found that offspring sired by preferred males were
      significantly more likely to survive the experimental infection compared to those
      sired by non-preferred males. We found no significant differences in the pathogen
      clearance or infection dynamics between the infected mice, suggesting that
      offspring from preferred males were better able to cope with infection and had
      improved tolerance rather than immune resistance. CONCLUSION: Our results provide
      the first direct experimental evidence within a single study that partner
      preferences enhance offspring resistance to infectious diseases.

PMID- 24450608
TI  - Evaluation of the impact of a psycho-educational intervention on knowledge levels
      and psychological outcomes for people diagnosed with Schizophrenia and their
      caregivers in Jordan: a randomized controlled trial.
AB  - BACKGROUND: Schizophrenia is one of the most serious forms of mental illness
      among people being treated in psychiatric clinics in developing and developed
      countries. Providing care for people diagnosed with schizophrenia can be
      stressful for their caregivers. Psycho-educational interventions may improve
      patients' and primary caregivers' knowledge of schizophrenia and impact
      positively on patients' physical and psychological outcomes and primary
      caregivers' burden of care and quality of life. Studies thus far have shown that
      these interventions may improve patients' and caregivers' outcomes, but the
      quality of included randomized controlled trials (RCTs) is poor and it is
      difficult to draw firm conclusions as to the effectiveness of such interventions
      on patients and primary caregivers' outcomes, hence the current study.
      METHODS/DESIGN: A randomized controlled trial in four outpatient mental health
      clinics in Jordan comparing psycho-educational interventions in the form of six
      booklets every fortnight, with treatment as usual in people diagnosed with
      schizophrenia and their primary caregivers. The primary outcome for participants
      is knowledge of Schizophrenia; secondary outcomes for patients are positive and
      negative symptoms of schizophrenia and relapse rate, while secondary outcomes for
      primary caregivers are burden of care and quality of life. All measures are
      assessed at baseline, immediately post-intervention and at three months follow
      up. DISCUSSION: This randomized control trial, conducted in Jordan among people
      living with schizophrenia and their primary caregivers, will assess the effect of
      psycho-educational interventions on knowledge of Schizophrenia, patients'
      positive and negative symptoms and quality of life, and caregivers' burden of
      care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78084871.

PMID- 24450609
TI  - Laridae: A neglected reservoir that could play a major role in avian influenza
      virus epidemiological dynamics.
AB  - Avian influenza viruses (AIVs) are of great concern worldwide due to their
      economic impact and the threat they represent to human health. As wild birds are
      the natural reservoirs of AIVs, understanding AIV dynamics in different avian
      taxa is essential for deciphering the epidemiological links between wildlife,
      poultry and humans. To date, only the Anatidae (ducks, geese and swans) have been
      widely studied. Here, we aim to shed light on the current state of knowledge on
      AIVs in Laridae (gulls, terns and kittiwakes) versus that in Anatidae by setting
      forth four fundamental questions: how, when, where and to which host species are
      AIVs transmitted? First, we describe ecological differences between Laridae and
      Anatidae and discuss how they may explain observed contrasts in preferential
      transmission routes and the evolution of specific AIV subtypes. Second, we
      highlight the dissimilarities in the temporal patterns of AIV shedding between
      Laridae and Anatidae and address the role that immunity likely plays in shaping
      these patterns. Third, we underscore that Laridae may be key in promoting
      intercontinental exchanges of AIVs. Finally, we emphasize the crucial
      epidemiological position that Laridae occupy between wildlife, domestic birds and
      humans. 

PMID- 24450610
TI  - Comment on Du Q, Wu B, Wang YJ, et al. Comparative effects of sitagliptin and
      metformin in patients with type 2 diabetes mellitus: a meta-analysis. Curr Med
      Res Opin 2013;29:1487-94.

PMID- 24450611
TI  - Temporal trend analysis of nurses' knowledge about implantable cardioverter
      defibrillators.
AB  - BACKGROUND: Although crucial, research on nurses' knowledge on the use of
      implantable cardioverter defibrillators (ICDs) is scant. The aims of the study
      were to investigate (i) the level of nurses' knowledge on care of patients with
      ICDs, (ii) whether knowledge level is related to education and type of hospital
      where nurses practice and (iii) whether knowledge level changes among nurses over
      time. METHODS: We developed a questionnaire comprising 27 items in four parts:
      (1) Sociodemographics, (2) Technical facts about ICDs, (3) Daily life challenges
      and (4) Self-evaluation of knowledge. After validation, surveys were conducted
      during 1-week cardiac educational courses in 2003-2010. In total, 463 nurses
      working in cardiology-related areas participated, yielding a response rate of
      91%. RESULTS: Practical and technical knowledge about ICDs was lacking. Nurses
      were unaware or did not know that mobile phones can affect the device (80%), that
      patients are restricted from driving heavy vehicles (69%), and that ICDs can
      deliver unintended shock therapy (73%). However, they were aware that ICD
      patients can resume sexual (87%) and physical activity (85%). There were few
      significant differences with regard to education and type of hospital where
      nurses practiced, but significant time trends in correct answers regarding
      kitchen appliances, resumption of physical activity and shock delivery.
      CONCLUSION: Over an 8-year period, despite the increased usage of ICDs, overall
      nurses had a lack of knowledge in relation to specific key clinical issues on the
      care of ICD patients. As a consequence, these patients may fail to receive
      qualified care. Future research should assess knowledge of other health care
      professionals and focus on interventions that increase and maintain an
      appropriate knowledge level in care of ICD patients. Relevance to clinical
      practice The level of nurses' knowledge on care of patients with ICDs needs to be
      systematically raised in order to ensure appropriate counselling and nursing
      care.

PMID- 24450612
TI  - Disseminating alcohol screening and brief intervention at trauma centers: a
      policy-relevant cluster randomized effectiveness trial.
AB  - BACKGROUND AND AIMS: In 2005 the American College of Surgeons passed a mandate
      requiring that level I trauma centers have mechanisms to identify and intervene
      with problem drinkers. The aim of this investigation was to determine if a multi
      level trauma center intervention targeting both providers and patients would lead
      to higher-quality alcohol screening and brief intervention (SBI) when compared
      with trauma center mandate compliance without implementation enhancements.
      DESIGN: Cluster randomized trial in which intervention site (site n = 10, patient
      n = 409) providers received 1-day workshop training on evidence-based
      motivational interviewing (MI) alcohol interventions and four 30-minute feedback
      and coaching sessions; control sites (site n = 10, patient n = 469) implemented
      the mandate without study team training enhancements. SETTING: Trauma centers in
      the United States of America. PARTICIPANTS: A total of 878 blood alcohol-positive
      in-patients with and without traumatic brain injury (TBI). MEASUREMENTS: MI
      skills of providers were assessed with fidelity coded standardized patient
      interviews. All patients were interviewed at baseline and 6- and 12-months post
      injury with the Alcohol Use Disorders Identification Test (AUDIT). FINDINGS:
      Intervention site providers consistently demonstrated enhanced MI skills compared
      with control providers. Intervention patients demonstrated an 8% reduction in
      AUDIT hazardous drinking relative to controls over the course of the year after
      injury (relative risk = 0.88, 95%, confidence interval = 0.79, 0.98).
      Intervention patients were more likely to demonstrate improvements in alcohol use
      problems in the absence of traumatic brain injury (TBI) (P = 0.002). CONCLUSION:
      Trauma center providers can be trained to deliver higher-quality alcohol
      screening and brief intervention (SBI) than untrained providers, which is
      associated with modest reductions in alcohol use problems, particularly among
      patients without TBI.

PMID- 24450614
TI  - Silica particle stability and settling in protic ionic liquids.
AB  - Silica particle suspensions of 10 wt % have been investigated in the protic ionic
      liquids (ILs) ethylammonium nitrate (EAN), ethanolammonium nitrate (EtAN),
      propylammonium nitrate (PAN), and dimethylethylammonium formate (DMEAF). Static
      and dynamic light scattering reveal that single particles coexist in dynamic
      equilibrium with flocculated networks at room temperature. These types of systems
      are classified as weakly flocculated and are quite rare. As weakly flocculated
      systems generally exist only within a narrow range of conditions, the effect of
      temperature was probed. When temperature is increased, the thermal motion of
      suspended particles increases, favoring dispersion, but in ILs suspensions,
      heating reduces the stabilizing effect of the interfacial structure of the IL.
      When subjected to a small increase in temperature, particle suspensions in ILs
      become unstable, indicated by the absence of a peak corresponding to single
      particles in the light scattering data. For EAN and DMEAF, further increasing
      temperatures above 40  degrees C returns the systems to a weakly flocculated
      state in which thermal energy is sufficient to break particles away from
      aggregates. Weakly flocculated suspensions in EAN and EtAN settle more rapidly
      than predicted by the Stokes equation, as the particles spend a significant
      portion of time in large, rapidly settling flocs. Surprisingly, suspensions in
      PAN and DMEAF settle slower than predicted. Oscillatory rheology indicates that
      these suspensions are viscoelastic, due to a persistent, long-range structure in
      the suspension that slows settling. In aggregated systems, settling is very
      rapid. 

PMID- 24450613
TI  - From meta-omics to causality: experimental models for human microbiome research.
AB  - Large-scale 'meta-omic' projects are greatly advancing our knowledge of the human
      microbiome and its specific role in governing health and disease states. A myriad
      of ongoing studies aim at identifying links between microbial community
      disequilibria (dysbiosis) and human diseases. However, due to the inherent
      complexity and heterogeneity of the human microbiome, cross-sectional, case
      control and longitudinal studies may not have enough statistical power to allow
      causation to be deduced from patterns of association between variables in high
      resolution omic datasets. Therefore, to move beyond reliance on the empirical
      method, experiments are critical. For these, robust experimental models are
      required that allow the systematic manipulation of variables to test the
      multitude of hypotheses, which arise from high-throughput molecular studies.
      Particularly promising in this respect are microfluidics-based in vitro co
      culture systems, which allow high-throughput first-pass experiments aimed at
      proving cause-and-effect relationships prior to testing of hypotheses in animal
      models. This review focuses on widely used in vivo, in vitro, ex vivo and in
      silico approaches to study host-microbial community interactions. Such systems,
      either used in isolation or in a combinatory experimental approach, will allow
      systematic investigations of the impact of microbes on the health and disease of
      the human host. All the currently available models present pros and cons, which
      are described and discussed. Moreover, suggestions are made on how to develop
      future experimental models that not only allow the study of host-microbiota
      interactions but are also amenable to high-throughput experimentation. 

PMID- 24450616
TI  - AtPEPTIDE RECEPTOR2 mediates the AtPEPTIDE1-induced cytosolic Ca(2+) rise, which
      is required for the suppression of Glutamine Dumper gene expression in
      Arabidopsis roots.
AB  - AtPEPTIDE RECEPTOR2 (AtPEPR2) is a member of leucine-rich repeat receptor-like
      kinase family and binds to a group of AtPROPEP gene-encoded endogenous peptides,
      AtPeps. Previously, we found that AtPEPR2 plays a moderate role in the AtPep1
      mediated innate immunity responses in Arabidopsis leaf. In this study, we found
      that AtPEPR2 promoter has strong activity in the vascular tissues of the roots
      and the atpepr2 mutants showed a moderate but significantly shorter root
      phenotype. AtPEPR2 partially mediated AtPep1-induced root elongation inhibition.
      AtPep1-triggered cytosolic Ca(2+) transient rise in roots showed partial
      dependence on AtPEPR2 and fully on extracellular Ca(2+) ([Ca(2+) ]ext ).
      Transcriptional profiling analysis found that expression of 75% of AtPep1
      modulated genes in roots was fully dependent on AtPEPR2, of which two
      dramatically induced genes showed partial dependence on the [Ca(2+) ]ext .
      Arabidopsis genome contains seven Glutamine Dumpers genes (AtGDUs), encoding
      amino acid exporters. Three of them (AtGDU2, 3, 5) were among the top 10 genes
      that were downregulated by AtPep1 through AtPEPR2 fully dependent pathway.
      Treatment with AtPep1 strongly suppressed promoter activity of AtGDU3 in roots,
      which was relieved by chelating [Ca(2+) ]ext . Arabidopsis overexpressing AtGDU3
      showed a shorter root phenotype and decreased sensitivity to the AtPep1-mediated
      inhibition of root elongation. Taken together, this study demonstrated a
      significant role of AtPEPR2 in the AtPep1-mediated signaling in the roots. 

PMID- 24450617
TI  - The clustering of diet, physical activity and sedentary behavior in children and
      adolescents: a review.
AB  - Diet, physical activity (PA) and sedentary behavior are important, yet
      modifiable, determinants of obesity. Recent research into the clustering of these
      behaviors suggests that children and adolescents have multiple obesogenic risk
      factors. This paper reviews studies using empirical, data-driven methodologies,
      such as cluster analysis (CA) and latent class analysis (LCA), to identify
      clustering patterns of diet, PA and sedentary behavior among children or
      adolescents and their associations with socio-demographic indicators, and
      overweight and obesity. A literature search of electronic databases was
      undertaken to identify studies which have used data-driven methodologies to
      investigate the clustering of diet, PA and sedentary behavior among children and
      adolescents aged 5-18 years old. Eighteen studies (62% of potential studies) were
      identified that met the inclusion criteria, of which eight examined the
      clustering of PA and sedentary behavior and eight examined diet, PA and sedentary
      behavior. Studies were mostly cross-sectional and conducted in older children and
      adolescents (>= 9 years). Findings from the review suggest that obesogenic
      cluster patterns are complex with a mixed PA/sedentary behavior cluster observed
      most frequently, but healthy and unhealthy patterning of all three behaviors was
      also reported. Cluster membership was found to differ according to age, gender
      and socio-economic status (SES). The tendency for older children/adolescents,
      particularly females, to comprise clusters defined by low PA was the most robust
      finding. Findings to support an association between obesogenic cluster patterns
      and overweight and obesity were inconclusive, with longitudinal research in this
      area limited. Diet, PA and sedentary behavior cluster together in complex ways
      that are not well understood. Further research, particularly in younger children,
      is needed to understand how cluster membership differs according to socio
      demographic profile. Longitudinal research is also essential to establish how
      different cluster patterns track over time and their influence on the development
      of overweight and obesity.

PMID- 24450618
TI  - Leishmaniasis in immunosuppressed individuals.
AB  - Leishmaniasis is a vector-born chronic infectious disease caused by a group of
      protozoan parasites of the genus Leishmania. Whereas most immunocompetent
      individuals will not develop disease after Leishmania infection,
      immunosuppression is a well-established risk factor for disease. The most severe
      form is visceral leishmaniasis (VL), which is typically fatal if untreated.
      Whereas human immunodeficiency virus (HIV) co-infection (VL-HIV) was initially
      mainly reported from southern Europe, it is now emerging in other regions,
      including East Africa, India, and Brazil. VL has also been found in a wide range
      of non-HIV-related immunosuppressive states, mainly falling under the realm of
      transplantation medicine, rheumatology, haematology, and oncology. Clinical
      presentation can be atypical in immunosuppressed individuals, being easily
      misdiagnosed or mistaken as a flare-up of the underlying disease. The best
      diagnostic approach is the combination of parasitological and serological or
      molecular methods. Liposomal amphotericin B is the drug of choice. Treatment
      failure and relapse rates are particularly high in cases of HIV co-infection,
      despite initiation of antiretroviral treatment. Primary prophylaxis is not
      recommended, but secondary prophylaxis is recommended when the patient is
      immunosuppressed. Cutaneous leishmaniasis can have a number of particular
      features in individuals with immunosuppression, especially if severe, including
      parasite dissemination, clinical polymorphism with atypical and often more severe
      clinical forms, and even visceralization. Mucosal leishmaniasis is more common.
      Treatment of cutaneous and mucosal leishmaniasis can be challenging, and systemic
      treatment is more often indicated. With globally increased travel and access to
      advanced medical care in developing countries, the leishmaniasis burden in
      immunosuppressed individuals will probably continue to rise, warranting increased
      awareness and enhanced surveillance systems.

PMID- 24450621
TI  - Rethinking the clockwork: redox cycles and non-transcriptional control of
      circadian rhythms.
AB  - Circadian rhythms are a hallmark of living organisms, observable in all walks of
      life from primitive bacteria to highly complex humans. They are believed to have
      evolved to co-ordinate the timing of biological and behavioural processes to the
      changing environmental needs brought on by the progression of day and night
      through the 24-h cycle. Most of the modern study of circadian rhythms has centred
      on so-called TTFLs (transcription-translation feedback loops), wherein a core
      group of 'clock' genes, capable of negatively regulating themselves, produce
      oscillations with a period of approximately 24 h. Recently, however, the
      prevalence of the TTFL paradigm has been challenged by a series of findings
      wherein circadian rhythms, in the form of redox reactions, persist in the absence
      of transcriptional cycles. We have found that circadian cycles of oxidation and
      reduction are conserved across all domains of life, strongly suggesting that non
      TTFL mechanisms work in parallel with the canonical genetic processes of
      timekeeping to generate the cyclical cellular and behavioural phenotypes that we
      commonly recognize as circadian rhythms. 

PMID- 24450620
TI  - In-silico analysis and expression profiling implicate diverse role of EPSPS
      family genes in regulating developmental and metabolic processes.
AB  - BACKGROUND: The EPSPS, EC 2.5.1.19 (5-enolpyruvylshikimate -3-phosphate synthase)
      is considered as one of the crucial enzyme in the shikimate pathway for the
      biosynthesis of essential aromatic amino acids and secondary metabolites in
      plants, fungi along with microorganisms. It is also proved as a specific target
      of broad spectrum herbicide glyphosate. RESULTS: On the basis of structure
      analysis, this EPSPS gene family comprises the presence of EPSPS I domain, which
      is highly conserved among different plant species. Here, we followed an in-silico
      approach to identify and characterize the EPSPS genes from different plant
      species. On the basis of their phylogeny and sequence conservation, we divided
      them in to two groups. Moreover, the interacting partners and co-expression data
      of the gene revealed the importance of this gene family in maintaining cellular
      and metabolic functions in the cell. The present study also highlighted the
      highest accumulation of EPSPS transcript in mature leaves followed by young
      leaves, shoot and roots of tobacco. In order to gain the more knowledge about
      gene family, we searched for the previously reported motifs and studied its
      structural importance on the basis of homology modelling. CONCLUSIONS: The
      results presented here is a first detailed in-silico study to explore the role of
      EPSPS gene in forefront of different plant species. The results revealed a great
      deal for the diversification and conservation of EPSPS gene family across
      different plant species. Moreover, some of the EPSPS from different plant species
      may have a common evolutionary origin and may contain same conserved motifs with
      related and important molecular function. Most importantly, overall analysis of
      EPSPS gene elucidated its pivotal role in immense function within the plant, both
      in regulating plant growth as well its development throughout the life cycle of
      plant. Since EPSPS is a direct target of herbicide glyphosate, understanding its
      mechanism for regulating developmental and cellular processes in different plant
      species would be a great revolution for developing glyphosate resistant crops.

PMID- 24450622
TI  - Protein kinase networks that limit TLR signalling.
AB  - TLRs (Toll-like receptors) detect invading micro-organisms which triggers the
      production of pro-inflammatory mediators needed to combat infection. Although
      these signalling networks are required to protect the host against invading
      pathogens, dysregulation of TLR pathways contributes to the development of
      chronic inflammatory diseases and autoimmune disorders. Molecular mechanisms have
      therefore evolved to restrict the strength of TLR signalling. In the present
      review, I highlight recent advances in our understanding of the protein kinase
      networks required to suppress the innate immune response by negatively regulating
      TLR signalling and/or promoting the secretion of anti-inflammatory cytokines. I
      present my discoveries on the key roles of the IKK (inhibitor of nuclear factor
      kappaB kinase)-related kinases and the SIKs (salt-inducible kinases) in limiting
      innate immunity within the greater context of the field. 

PMID- 24450623
TI  - Discontinuous leading-strand synthesis: a stop-start story.
AB  - Reconstitution experiments using replication proteins from a number of different
      model organisms have firmly established that, in vitro, DNA replication is semi
      discontinuous: continuous on the leading strand and discontinuous on the lagging
      strand. The mechanism by which DNA is replicated in vivo is less clear. In fact,
      there have been many observations of discontinuous replication in the absence of
      exogenous DNA-damaging agents. It has also been proposed that replication is
      discontinuous on the leading strand at least in part because of DNA lesion
      bypass. Several recent studies have revealed mechanistic details of pathways
      where replication of the leading strand introduces discontinuities. These
      mechanisms and their potential contributions to observations of discontinuous
      replication in vivo will be discussed. 

PMID- 24450624
TI  - Functional implications of assigned, assumed and assembled PKC structures.
AB  - The empirical derivation of PKC (protein kinase C) domain structures and those
      modelled by homology or imputed from protein behaviour have been extraordinarily
      valuable both in the elucidation of PKC pathway mechanisms and in the general
      lessons that extrapolate to other signalling pathways. For PKC family members,
      there are many domain/subdomain structures and models, covering all of the known
      domains, variably present in this family of protein serine/threonine kinases (C1,
      C2, PB1, HR1, kinase domains). In addition to these structures, there are a
      limited number of complexes defined, including the structure of the PKCepsilon V3
      14-3-3 complex. In the context of structure-driven insights into PKC pathways,
      there are several broadly applicable principles and mechanisms relevant to the
      operation of and intervention in signalling pathways. These principles have an
      impact in unexpected ways, from the regulation of membrane targeting, through
      strategies for pharmacological intervention, to biomarkers. 

PMID- 24450625
TI  - Regulating the level of intracellular hydrogen peroxide: the role of
      peroxiredoxin IV.
AB  - Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell
      cycle as well as contributing towards the oxidative stress response. The primary
      target of this molecule is oxidation-sensitive cysteine residues in proteins such
      as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2
      that need to be regulated for H2O2 to react with and modify protein thiols. In
      particular, the family of peroxiredoxins are capable of the rapid removal of even
      trace amounts of this molecule. It has been suggested that the inactivation of
      peroxiredoxins by hyperoxidation may allow H2O2 levels to increase in cells and
      thereby modify critical thiol groups in proteins. We have been studying how the
      H2O2 produced during disulfide formation in the ER (endoplasmic reticulum) is
      metabolized and have shown that ER-resident peroxiredoxin IV not only can remove
      H2O2, but also contributes to de novo disulfide formation. In the present
      article, we review recent data on the structure and function of this enzyme as
      well as its sensitivity to hyperoxidation. 

PMID- 24450626
TI  - Explorations of time and electrochemical potential: opportunities for fresh
      perspectives on signalling proteins.
AB  - Apoptosis is triggered by an accumulation of ROS (reactive oxygen species)
      produced by proteins of the mitochondrial respiratory chain. The levels of ROS
      are controlled by the activities of mitochondrial redox proteins such as
      glutaredoxin 2 that help to modulate the susceptibility of a cell to apoptosis.
      However, once downstream events have resulted in the release of cytochrome c to
      the cytosol, it is widely considered that cell death is inevitable. Cytochrome c
      may promote its own release from mitochondria through interactions with the
      mitochondrial phospholipid cardiolipin (diphosphatidylglycerol). In the present
      article, spectroelectrochemistry of the cardiolipin complex of cytochrome c and
      protein film electrochemistry of glutaredoxin 2 are reviewed to illustrate how
      electrochemical methods provide insight into the properties of signalling
      proteins. 

PMID- 24450627
TI  - Structure and function of RLIP76 (RalBP1): an intersection point between Ras and
      Rho signalling.
AB  - RLIP76 (Ral-interacting protein of 76 kDa) [also known as RalBP1 (Ral-binding
      protein 1)] is an effector for the Ral family small GTPases. RLIP76 has been
      implicated in a number of cell processes, including receptor-mediated
      endocytosis, cell migration, mitochondrial division and metabolite transport.
      RLIP76 has two recognizable domains in the centre of the protein sequence: a GAP
      (GTPase-activating protein) domain for the Rho family G-proteins and an RBD (Ral
      binding domain). The remainder of RLIP76 has no discernable homology with other
      proteins. The RBD forms a simple coiled-coil of two alpha-helices, which
      interacts with RalB by binding to both of the nucleotide-sensitive 'switch'
      regions. Both of these RLIP76 helices are involved in the interaction with Ral,
      but the interhelix loop is left free. This is the location of one of the two ATP
      binding sites that have been identified in RLIP76 and suggests that Ral
      interaction would not prevent ATP binding. The structure of the RhoGAP-RBD dyad
      shows that the two domains are fixed in their orientation by a relatively rigid
      linker. This domain arrangement allows the two domains to engage Rho family and
      Ral small G-proteins simultaneously at the membrane. This suggests that RLIP76 is
      a node for Rho and Ras family signalling. 

PMID- 24450628
TI  - Regulation of IL-6-type cytokine responses by MAPKs.
AB  - IL-6 (interleukin 6)-type cytokines are pleiotropic molecules, critical for
      cellular homoeostasis and with well-recognized roles in several human diseases.
      They all activate JAK (Janus kinase)/STAT (signal transducer and activator of
      transcription) signalling and, depending on the particular cytokine, cell type
      and cellular environment, they can also trigger the activation of MAPK (mitogen
      activated protein kinase) and PI3K (phosphoinositide 3-kinase) cascades. Although
      it is clear that JAK/STAT and MAPK reciprocally regulate each other, how these
      signalling pathways are fully integrated remains to be fully understood. Not only
      do cells have to be able to integrate and conciliate what are often contradictory
      signalling cues, but they are also subject to complex regulatory mechanisms
      involving these pathways. More specifically, we have shown recently that ERK2
      (extracellular-signal-regulated kinase 2) is required for the transcriptional
      regulation of gp130 (glycoprotein 130), a key receptor complex component for most
      IL-6-type cytokines. ERK2 not only binds to the gp130 promoter and is required
      for full expression of the protein, but it also regulates the stability of gp130
      mRNA. This function of ERK2 is not shared by ERK1 and it probably represents an
      entirely novel function for this prominent kinase. 

PMID- 24450629
TI  - Structural organization of signalling to and from IP3 receptors.
AB  - In the 30 years since IP3 (inositol 1,4,5-trisphosphate) was first shown to
      release Ca2+ from intracellular stores, the importance of spatially organized
      interactions within IP3-regulated signalling pathways has been universally
      recognized. Recent evidence that addresses three different levels of the
      structural determinants of IP3-evoked Ca2+ signalling is described in the present
      review. High-resolution structures of the N-terminal region of the IP3R (IP3
      receptor) have established that the two essential phosphate groups of IP3 bind to
      opposite sides of the IP3-binding site, pulling its two domains together. This
      conformational change is proposed to disrupt an interaction between adjacent
      subunits within the tetrameric IP3R that normally holds the channel in a closed
      state. Similar structural changes are thought to allow gating of ryanodine
      receptors. cAMP increases the sensitivity of IP3Rs and thereby potentiates the
      Ca2+ signals evoked by receptors that stimulate IP3 formation. We speculate that
      both IP3 and cAMP are delivered to IP3Rs within signalling junctions, wherein the
      associated IP3Rs are exposed to a saturating concentration of either messenger.
      The concentration-dependent effects of extracellular stimuli come from
      recruitment of junctions rather than from a graded increase in the activity of
      individual junctions. IP3Rs within 'IP3 junctions' respond directly to receptors
      that stimulate phospholipase C, whereas extra-junctional IP3Rs are exposed to
      suboptimal concentrations of IP3 and open only when they are sensitized by cAMP.
      These results highlight the importance of selective delivery of diffusible
      messengers to IP3Rs. The spatial organization of IP3Rs also allows them to direct
      Ca2+ to specific intracellular targets that include other IP3Rs, mitochondria and
      Ca2+-regulated channels and enzymes. IP3Rs also interact functionally with
      lysosomes because Ca2+ released by IP3Rs, but not that entering cells via store
      operated Ca2+ entry pathways, is selectively accumulated by lysosomes. This Ca2+
      uptake shapes the Ca2+ signals evoked by IP3 and it may regulate lysosomal
      behaviour. 

PMID- 24450630
TI  - AMPK: a cellular energy sensor primarily regulated by AMP.
AB  - AMPK (AMP-activated protein kinase) is a cellular energy sensor that monitors the
      ratio of AMP/ATP, and possibly also ADP/ATP, inside cells. Once activated by
      falling cellular energy levels, it acts to restore energy homoeostasis by
      switching on catabolic pathways that generate ATP, while switching off anabolic
      pathways and other processes consuming ATP. AMPK is switched on by increases in
      AMP via three mechanisms, all of which are antagonized by ATP: (i) promotion of
      phosphorylation of Thr172 by upstream activating kinases; (ii) inhibition of
      dephosphorylation of Thr172 by phosphatases; and (iii) allosteric activation of
      the phosphorylated kinase. Recently, it has been proposed that the first two
      mechanisms are also triggered by ADP, which might be the physiological signal
      rather than AMP, and that the third mechanism may not be physiologically
      significant. We have re-evaluated these questions, and found that only mechanism
      (ii) is mimicked by ADP, and that ADP is also less potent than AMP, which we
      still believe to be the primary signal. We have also provided evidence that
      mechanism (iii), i.e. allosteric activation by AMP, is a quantitatively
      significant mechanism in intact cells. 

PMID- 24450631
TI  - NF-kappaB and the cell cycle.
AB  - The NF-kappaB (nuclear factor kappaB) transcription factor family is a
      pleiotropic regulator of many cellular pathways, providing a mechanism for the
      cell to respond to a wide variety of stimuli and environmental challenges. It is
      not surprising therefore that an important component of NF-kappaB's function
      includes regulation of the cell cycle. However, this aspect of its behaviour is
      often overlooked and receives less attention than its ability to induce
      inflammatory gene expression. In the present article, we provide an updated
      review of the current state of our knowledge about integration of NF-kappaB
      activity with cell cycle regulation, including newly characterized direct and
      indirect target genes in addition to the mechanisms through which NF-kappaB
      itself can be regulated by the cell cycle. 

PMID- 24450632
TI  - PARP inhibitors for anticancer therapy.
AB  - PARP-1 [poly(ADP-ribose) polymerase-1], which plays a key role in DNA repair, was
      discovered 50 years ago. PARPi (PARP inhibitors), originally made to probe the
      function of the enzyme, inhibit DNA repair and increase the potency of anticancer
      cytotoxic agents. PARPi of increasing potency were developed as chemo- and radio
      sensitizers and first entered clinical trial in cancer patients in 2003. However,
      it was the revelation in 2005 that they were synthetically lethal in cells with
      DNA repair defects, found almost exclusively in some tumours, that led to a major
      interest in this class of drug. Several PARPi have entered clinical trials and
      show promising activity in breast, ovarian and other cancers associated with BRCA
      (breast cancer early-onset) mutations or other defects in homologous
      recombination DNA repair. It is likely that at least one of these will be
      licensed soon. The present review describes key events from the discovery to
      clinical application of PARPi. 

PMID- 24450633
TI  - cAMP signalling in the vasculature: the role of Epac (exchange protein directly
      activated by cAMP).
AB  - The second messenger cAMP plays a central role in mediating vascular smooth
      muscle relaxation in response to vasoactive transmitters and in strengthening
      endothelial cell-cell junctions that regulate the movement of solutes, cells and
      macromolecules between the blood and the surrounding tissue. The vasculature
      expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic
      nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange
      proteins directly activated by cAMP). Epacs are a family of GEFs (guanine
      nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and
      are being increasingly implicated as important mediators of cAMP signalling, both
      in their own right and in parallel with the prototypical cAMP target PKA. In the
      present paper, we review what is currently known about the role of Epac within
      blood vessels, particularly with regard to the regulation of vascular tone,
      endothelial barrier function and inflammation. 

PMID- 24450634
TI  - Functions of inorganic polyphosphates in eukaryotic cells: a coat of many
      colours.
AB  - PolyP (inorganic polyphosphate) is a linear polymer of tens to hundreds of
      orthophosphate residues linked by high-energy phosphoanhydride bonds. This
      polymer is present in all living organisms from bacteria to mammals. Until
      recently, most of the studies on polyP have focused on its function in
      prokaryotes. In prokaryotes, polyP has been implicated in many unrelated
      processes ranging from basic metabolism to structural functions. However, polyP
      analysis and function in higher eukaryotes has been gaining momentum recently. In
      the present review, we mainly aim to discuss the proposed intracellular functions
      of polyP in higher eukaryotes and its detection methods. 

PMID- 24450635
TI  - New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases.
AB  - E3 ubiquitin ligases that direct substrate proteins to the ubiquitin-proteasome
      system are promising, though largely unexplored drug targets both because of
      their function and their remarkable specificity. CRLs [Cullin-RING (really
      interesting new gene) ligases] are the largest group of E3 ligases and function
      as modular multisubunit complexes constructed around a Cullin-family scaffold
      protein. The Cul3-based CRLs uniquely assemble with BTB (broad
      complex/tramtrack/bric-a-brac) proteins that also homodimerize and perform the
      role of both the Cullin adapter and the substrate-recognition component of the
      E3. The most prominent member is the BTB-BACK (BTB and C-terminal Kelch)-Kelch
      protein KEAP1 (Kelch-like ECH-associated protein 1), a master regulator of the
      oxidative stress response and a potential drug target for common conditions such
      as diabetes, Alzheimer's disease and Parkinson's disease. Structural
      characterization of BTB-Cul3 complexes has revealed a number of critical assembly
      mechanisms, including the binding of an N-terminal Cullin extension to a
      bihelical '3-box' at the C-terminus of the BTB domain. Improved understanding of
      the structure of these complexes should contribute significantly to the effort to
      develop novel therapeutics targeted to CRL3-regulated pathways. 

PMID- 24450636
TI  - Structures of soluble guanylate cyclase: implications for regulatory mechanisms
      and drug development.
AB  - Activation of cGMP synthesis leads to vasodilation, and is an important mechanism
      in clinical treatment of angina, heart failure, and severe peripheral and
      pulmonary hypertension. The nitric oxide-responsive sGC (soluble guanylate
      cyclase) has been the target of recent drug discovery efforts. The present review
      surveys recent data on the structure and regulation of sGC, and the prospects of
      new avenues for therapeutic intervention. 

PMID- 24450637
TI  - Structure-function relationships and supramolecular organization of the EGFR
      (epidermal growth factor receptor) on the cell surface.
AB  - Dimerization and higher-order oligomerization are believed to play an important
      role in the activation of the EGFR (epidermal growth factor receptor).
      Understanding of the process has been limited by the lack of availability of
      suitable methods for the measurement in cells of distances in the range 10-100
      nm, too short for imaging methods and too long for spectroscopic methods such as
      FRET. In the present article, we review the current state of our knowledge of
      EGFR oligomerization, and describe results from a new single-molecule
      localization method that has allowed the quantitative characterization of the
      distribution of EGFR-EGFR distances in cells. Recent data suggest the involvement
      of cortical actin in regulating the formation of EGFR complexes. 

PMID- 24450638
TI  - Structure, function and inhibition of the phosphoinositide 3-kinase p110alpha
      enzyme.
AB  - The PI3K (phosphoinositide 3-kinase) p110alpha isoform is activated by oncogenic
      mutations in many cancers. This has stimulated intense interest in identifying
      inhibitors of the PI3K pathway as well as p110alpha-selective inhibitors, and
      understanding the mechanisms underlying activation by the oncogenic mutations. In
      the present article, we review recent progress in the structure and function of
      the p110alpha enzyme and two of its most common oncogenic mutations, the
      development of isoform-selective inhibitors, and p110alpha pharmacology. 

PMID- 24450639
TI  - New strategies for the treatment of ovarian cancer.
AB  - Ovarian cancer usually responds well to chemotherapy, but once the disease
      becomes resistant to chemotherapy, the treatment options available are
      inadequate. A number of strategies are currently undergoing clinical evaluation,
      among which angiogenesis and PARP [poly(ADP-ribose) polymerase] inhibitors appear
      promising. Pre-clinical studies have identified several potential new therapeutic
      strategies, and we review the potential for use of BH3 (Bcl-2 homology) mimetics,
      autotaxin inhibitors and statins to treat ovarian cancer. 

PMID- 24450640
TI  - Recent advances in the structural molecular biology of Ets transcription factors:
      interactions, interfaces and inhibition.
AB  - The Ets family of eukaryotic transcription factors is based around the conserved
      Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically
      and structurally well characterized, structures of homodimeric and ternary
      complexes point to Ets domains functioning as versatile protein-interaction
      modules. In the present paper, we review the progress made over the last decade
      to elucidate the structural mechanisms involved in modulation of DNA binding and
      protein partner selection during dimerization. We see that Ets domains, although
      conserved around a core architecture, have evolved to utilize a variety of
      interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic
      interfaces for both DNA and protein interaction. Furthermore, we discuss recent
      advances in drug development for inhibition of Ets factors, and the roles
      structural biology can play in their future. 

PMID- 24450642
TI  - HDX-MS takes centre stage at unravelling kinase dynamics.
AB  - In recent years, HDX-MS (hydrogen-deuterium exchange coupled to MS) on
      biomolecules has evolved from a niche technique to a powerful method in the
      investigation of protein dynamics. Protein kinases, in particular, represent an
      area of active study using this technique owing to their well-characterized
      protein structures and their relevance to diseases such as cancer, immune
      disorders and neurodegenerative defects. In the present review, we describe how
      HDX-MS has revealed important dynamic properties of protein kinases and provided
      insight into the mechanisms of drug binding. 

PMID- 24450641
TI  - Allosteric linkers in cAMP signalling.
AB  - Weak interactions mediated by dynamic linkers are key determinants of allosteric
      regulation in multidomain signalling proteins. However, the mechanisms of linker
      dependent control have remained largely elusive. In the present article, we
      review an allosteric model introduced recently to explain how signalling proteins
      effectively sense and respond to weak interactions, such as those elicited by
      flexible linkers flanking globular domains. Central to this model is the idea
      that near degeneracy within the free energy landscape of conformational selection
      maximally amplifies the response to weak (~2RT), but conformation-selective
      interactions. The model was tested as proof of principle using the prototypical
      regulatory subunit (R) of protein kinase A and led to the unanticipated finding
      that dynamic linkers control kinase activation and inhibition by tuning the
      inhibitory pre-equilibrium of a minimally populated intermediate (apo R). A
      practical implication of the proposed model is a new strategy to design kinase
      inhibitors with enhanced potency through frustration-relieving mutations. 

PMID- 24450643
TI  - Control and regulation of mRNA translation.
AB  - Translational control is central to the gene expression pathway and was the focus
      of the 2013 annual Translation UK meeting held at the University of Kent. The
      meeting brought together scientists at all career stages to present and discuss
      research in the mRNA translation field, with an emphasis on the presentations on
      the research of early career scientists. The diverse nature of this field was
      represented by the broad range of papers presented at the meeting. The complexity
      of mRNA translation and its control is emphasized by the interdisciplinary
      research approaches required to address this area with speakers highlighting
      emerging systems biology techniques and their application to understanding mRNA
      translation and the network of pathways controlling it. 

PMID- 24450644
TI  - Challenges and obstacles related to solving the codon bias riddles.
AB  - Dozens of papers have been written about the relationship between codon bias,
      transcript features and gene translation. Even though answering these questions
      may sound straightforward, apparently many of these studies seem to contradict
      each other. In the present article, I provide four major non-mutually exclusive
      explanations related to this issue: (i) there are dozens of related relevant
      variables with unknown causal relationships; (ii) various biases in the relevant
      experimental data; (iii) drawing conclusions from specific examples; and (iv)
      challenges in experimentally modifying one biological variable without affecting
      the system via multiple biological feedback mechanisms. Specifically, some of the
      contradictions can be settled when considering these four points and/or via a
      multidisciplinary approach. The discussion reported in the present article is
      also relevant to many other biological/medical questions/fields. 

PMID- 24450645
TI  - Controlling translation elongation efficiency: tRNA regulation of ribosome flux
      on the mRNA.
AB  - Gene expression can be regulated by a wide variety of mechanisms. One example
      concerns the growing body of evidence that the protein-production rate can be
      regulated at the level of translation elongation by controlling ribosome flux
      across the mRNA. Variations in the abundance of tRNA molecules cause different
      rates of translation of their counterpart codons. This, in turn, produces a
      variable landscape of translational rate across each and every mRNA, with the
      dynamic formation and deformation of ribosomal queues being regulated by both
      tRNA availability and the rates of translation initiation and termination. In the
      present article, a range of examples of tRNA control of gene expression are
      reviewed, and the use of mathematical modelling to develop a predictive
      understanding of the consequences of that regulation is discussed and explained.
      These findings encourage a view that predicting the protein-synthesis rate of
      each mRNA requires a holistic understanding of how each stage of translation,
      including elongation, contributes to the overall protein-production rate. 

PMID- 24450646
TI  - The diverse roles of the eIF4A family: you are the company you keep.
AB  - The eIF4A (eukaryotic initiation factor 4A) proteins belong to the extensive DEAD
      box RNA helicase family, the members of which are involved in many aspects of RNA
      metabolism by virtue of their RNA-binding capacity and ATPase activity. Three
      eIF4A proteins have been characterized in vertebrates: eIF4A1 and eIF4A2 are
      cytoplasmic, whereas eIF4A3 is nuclear-localized. Although highly similar, they
      have been shown to possess rather diverse roles in the mRNA lifecycle. Their
      specific and diverse functions are often regulated and dictated by interacting
      partner proteins. The key differences between eIF4A family members are discussed
      in the present review. 

PMID- 24450647
TI  - The translational machinery is an optimized molecular network that affects
      cellular homoeostasis and disease.
AB  - Translation involves interactions between mRNAs, ribosomes, tRNAs and a host of
      translation factors. Emerging evidence on the eukaryotic translational machinery
      indicates that these factors are organized in a highly optimized network, in
      which the levels of the different factors are finely matched to each other. This
      optimal factor network is essential for producing proteomes that result in
      optimal fitness, and perturbations to the optimal network that significantly
      affect translational activity therefore result in non-optimal proteomes, fitness
      losses and disease. On the other hand, experimental evidence indicates that
      translation and cell growth are relatively robust to perturbations, and viability
      can be maintained even upon significant damage to individual translation factors.
      How the eukaryotic translational machinery is optimized, and how it can maintain
      optimization in the face of changing internal parameters, are open questions
      relevant to the interaction between translation and cellular disease states. 

PMID- 24450648
TI  - Pleiotropic molecular effects of the Mycobacterium ulcerans virulence factor
      mycolactone underlying the cell death and immunosuppression seen in Buruli ulcer.
AB  - Mycolactone is a polyketide macrolide lipid-like secondary metabolite synthesized
      by Mycobacterium ulcerans, the causative agent of BU (Buruli ulcer), and is the
      only virulence factor for this pathogen identified to date. Prolonged exposure to
      high concentrations of mycolactone is cytotoxic to diverse mammalian cells
      (albeit with varying efficiency), whereas at lower doses it has a spectrum of
      immunosuppressive activities. Combined, these pleiotropic properties have a
      powerful influence on local and systemic cellular function that should explain
      the pathophysiology of BU disease. The last decade has seen significant advances
      in our understanding of the molecular mechanisms underlying these effects in a
      range of different cell types. The present review focuses on the current state of
      our knowledge of mycolactone function, and its molecular and cellular targets,
      and seeks to identify commonalities between the different functional and cellular
      systems. Since mycolactone influences fundamental cellular processes (cell
      division, cell death and inflammation), getting to the root of how mycolactone
      achieves this could have a profound impact on our understanding of eukaryotic
      cell biology. 

PMID- 24450649
TI  - mRNA deadenylation by Pan2-Pan3.
AB  - Poly(A) tails are important regulators of mRNA stability and translational
      efficiency. Cytoplasmic removal of poly(A) tails by 3'->5' exonucleases
      (deadenylation) is the rate-limiting step in mRNA degradation. Two exonuclease
      complexes contribute the majority of the deadenylation activity in eukaryotes:
      Ccr4-Not and Pan2-Pan3. These can be specifically recruited to mRNA to regulate
      mRNA stability or translational efficiency, thereby fine-tuning gene expression.
      In the present review, we discuss the activities and roles of the Pan2-Pan3
      deadenylation complex. 

PMID- 24450651
TI  - Tight junction regulation through vesicle trafficking: bringing cells together.
AB  - Epithelial layers are integral for many physiological processes and are
      maintained by intercellular adhesive structures. During disease, these structures
      can disassemble, leading to breakdown of epithelia. TJs (tight junctions) are one
      type of intercellular adhesion. Loss of TJs has been linked to the pathogenesis
      of many diseases. The present review focuses on the role of vesicle trafficking
      in regulation of TJs, in particular trafficking of the TJ protein occludin. We
      examine how endocytosis and endosomal recycling modulate occludin localization
      under steady-state conditions and during stimulated TJ disassembly. 

PMID- 24450650
TI  - Dynamics of ezrin and EBP50 in regulating microvilli on the apical aspect of
      epithelial cells.
AB  - Microvilli are found on the apical surface of epithelial cells. Recent studies on
      the microvillar proteins ezrin and EBP50 (ezrin/radixin/moesin-binding
      phosphoprotein of 50 kDa) have revealed both the dynamics and the regulation of
      microvillar components, and how a dynamic ezrin phosphocycle is necessary to
      confine microvilli to the apical membrane. In the present review, we first
      summarize the background to allow us to place these advances in context. 

PMID- 24450652
TI  - Cdc42 regulates polarized growth and cell integrity in fission yeast.
AB  - Polarized cell growth requires a well-orchestrated number of events, namely
      selection of growth site, organization of cytoskeleton elements and delivery of
      new material to the growth region. The small Rho GTPase Cdc42 has emerged as a
      major organizer of polarized growth through its participation in many of these
      events. In the present short review, we focus on the regulation of Cdc42 activity
      and localization as well as how it controls downstream events necessary for
      polarized cell growth in Schizosaccharomyces pombe. Owing to the high level of
      similarity of the polarity pathways, analogies between fission yeast and other
      model systems can be useful to decipher how cells can actively define their shape
      by polarized growth. 

PMID- 24450653
TI  - Rho GTPase-phosphatidylinositol phosphate interplay in fungal cell polarity.
AB  - Rho G-proteins and phosphatidylinositol phosphates, which are important for
      exocytosis, endocytosis and cytoskeleton organization, are key regulators of
      polarized growth in a range of organisms. The aim of the present brief review is
      to highlight recent findings and their implications with respect to the functions
      and interplay between Rho G-proteins and phosphatidylinositol phosphates in
      highly polarized fungal filamentous growth. 

PMID- 24450654
TI  - Rho-GTPase-regulated vesicle trafficking in plant cell polarity.
AB  - ROPs (Rho of plants) belong to a large family of plant-specific Rho-like small
      GTPases that function as essential molecular switches to control diverse cellular
      processes including cytoskeleton organization, cell polarization, cytokinesis,
      cell differentiation and vesicle trafficking. Although the machineries of vesicle
      trafficking and cell polarity in plants have been individually well addressed,
      how ROPs co-ordinate those processes is still largely unclear. Recent progress
      has been made towards an understanding of the co-ordination of ROP signalling and
      trafficking of PIN (PINFORMED) transporters for the plant hormone auxin in both
      root and leaf pavement cells. PIN transporters constantly shuttle between the
      endosomal compartments and the polar plasma membrane domains, therefore the
      modulation of PIN-dependent auxin transport between cells is a main developmental
      output of ROP-regulated vesicle trafficking. The present review focuses on these
      cellular mechanisms, especially the integration of ROP-based vesicle trafficking
      and plant cell polarity. 

PMID- 24450655
TI  - Elucidating the regulation of complex signalling systems in plant cells.
AB  - The pollen tube represents a model system for the study of tip growth, and the
      root provides a valuable system to study gene and signalling networks in plants.
      In the present article, using the two systems as examples, we discuss how to
      elucidate the regulation of complex signalling systems in plant cells. First, we
      discuss how hormones and related genes in plant root development form a complex
      interacting network, and their activities are interdependent. Therefore their
      roles in root development must be analysed as an integrated system, and
      elucidation of the regulation of each component requires the adaptation of a
      novel modelling methodology: regulation analysis. Secondly, hydrodynamics, cell
      wall and ion dynamics are all important properties that regulate plant cell
      growth. We discuss how regulation analysis can be applied to study the regulation
      of hydrodynamics, cell wall and ion dynamics, using pollen tube growth as a model
      system. Finally, we discuss future prospects for elucidating the regulation of
      complex signalling systems in plant cells. 

PMID- 24450657
TI  - Cutaneous collagenous vasculopathy: report of a case.

PMID- 24450660
TI  - High specific monoclonal antibody production and development of an ELISA method
      for monitoring T-2 toxin in rice.
AB  - This research produced a highly-specific and sensitive anti-T-2 toxin monoclonal
      antibody (mAb), and developed a rapid and sensitive competitive indirect enzyme
      linked immunosorbent assay (ELISA) method for monitoring T-2 toxin in rice. The
      mAb showed a negligible cross-reactivity value (CR) to most of the mycotoxins,
      and it could specifically bind to T-2 toxin without other mycotoxins, including
      HT-2 toxin (CR value at 3.08%), which exhibited a similar structure to T-2 toxin.
      The limit of detection (LOD) value, measured by IC10, was 5.80 MUg/kg. In spiked
      samples, mean recoveries ranged from 72.0% to 108.5% with intraday and interday
      variation less than 16.8 and 13.7%. This proposed protocol was significantly
      confirmed by a reliable ultrahigh performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) method and significant correlation was obtained. 

PMID- 24450656
TI  - Comparative analysis of the complete genome of KPC-2-producing Klebsiella
      pneumoniae Kp13 reveals remarkable genome plasticity and a wide repertoire of
      virulence and resistance mechanisms.
AB  - BACKGROUND: Klebsiella pneumoniae is an important opportunistic pathogen
      associated with nosocomial and community-acquired infections. A wide repertoire
      of virulence and antimicrobial resistance genes is present in K. pneumoniae
      genomes, which can constitute extra challenges in the treatment of infections
      caused by some strains. K. pneumoniae Kp13 is a multidrug-resistant strain
      responsible for causing a large nosocomial outbreak in a teaching hospital
      located in Southern Brazil. Kp13 produces K. pneumoniae carbapenemase (KPC-2) but
      is unrelated to isolates belonging to ST 258 and ST 11, the main clusters
      associated with the worldwide dissemination of KPC-producing K. pneumoniae. In
      this report, we perform a genomic comparison between Kp13 and each of the
      following three K. pneumoniae genomes: MGH 78578, NTUH-K2044 and 342. RESULTS: We
      have completely determined the genome of K. pneumoniae Kp13, which comprises one
      chromosome (5.3 Mbp) and six plasmids (0.43 Mbp). Several virulence and
      resistance determinants were identified in strain Kp13. Specifically, we detected
      genes coding for six beta-lactamases (SHV-12, OXA-9, TEM-1, CTX-M-2, SHV-110 and
      KPC-2), eight adhesin-related gene clusters, including regions coding for types 1
      (fim) and 3 (mrk) fimbrial adhesins. The rmtG plasmidial 16S rRNA
      methyltransferase gene was also detected, as well as efflux pumps belonging to
      five different families. Mutations upstream the OmpK35 porin-encoding gene were
      evidenced, possibly affecting its expression. SNPs analysis relative to the
      compared strains revealed 141 mutations falling within CDSs related to drug
      resistance which could also influence the Kp13 lifestyle. Finally, the genetic
      apparatus for synthesis of the yersiniabactin siderophore was identified within a
      plasticity region. Chromosomal architectural analysis allowed for the detection
      of 13 regions of difference in Kp13 relative to the compared strains.
      CONCLUSIONS: Our results indicate that the plasticity occurring at many
      hierarchical levels (from whole genomic segments to individual nucleotide bases)
      may play a role on the lifestyle of K. pneumoniae Kp13 and underlie the
      importance of whole-genome sequencing to study bacterial pathogens. The general
      chromosomal structure was somewhat conserved among the compared bacteria, and
      recombination events with consequent gain/loss of genomic segments appears to be
      driving the evolution of these strains.

PMID- 24450661
TI  - Pending structural modifications for the AJR.

PMID- 24450663
TI  - Section editor's notebook: breast cancer screening and overdiagnosis unmasked.

PMID- 24450662
TI  - Imaging features of primary and metastatic malignant perivascular epithelioid
      cell tumors.
AB  - OBJECTIVE: The objective of our study was to describe the imaging features of
      primary and metastatic malignant perivascular epithelioid cell tumors (PEComas).
      MATERIALS AND METHODS: In this retrospective study, 36 patients (26 women, 10
      men; mean age, 53.1 years; age range, 35-77 years) with a histopathologically
      confirmed diagnosis of malignant PEComa who were seen at our institute between
      January 2007 and December 2012 were included. Pretreatment imaging of the primary
      tumor in 17 patients (CT, n = 13; MRI, n = 9; ultrasound, n = 5) and follow-up
      imaging in all 36 patients (CT, n = 36; MRI, n = 7) were reviewed by three
      radiologists in consensus. RESULTS: The most common site of presentation of
      malignant PEComas was the retroperitoneum (38.9%) followed by the female genital
      tract (27.8%). Kidneys (8/36) and uterus (8/36) were the organs most frequently
      involved. The mean largest dimension was 11.01 cm (range, 4.5-25 cm). Primary
      tumors were well-circumscribed masses (16/17), were heteroechoic on ultrasound
      (5/5), were hypodense (2/6) to isodense (4/6) enhanced significantly (11/12) and
      compared with the paraspinal muscles on CT, were hypointense to isointense
      compared with skeletal muscle on T1-weighted imaging (8/9), were heterogeneously
      hyperintense compared with skeletal muscle on T2-weighted imaging (9/9), and
      showed significant post-gadolinium enhancement (7/7) on MRI. Of the 17 primary
      tumors, necrosis was seen in seven tumors, hemorrhage in three tumors, and
      calcification in three tumors. Twenty-six of 36 (72%) patients developed
      metastases, most commonly to the lung (21.6%), liver (17.6%), and peritoneum
      (10.8%). CONCLUSION: Malignant PEComas in our study were large tumors that most
      often arise in the kidneys and uterus and metastasize to lungs, liver, or
      peritoneum. In our experience malignant PEComas should be considered in the
      differential diagnosis of large well-circumscribed renal and uterine tumors.

PMID- 24450664
TI  - Imaging of breast cancer-related changes after surgical therapy.
AB  - OBJECTIVE: The purpose of this article is to discuss the surgical treatment of
      breast cancer and its resultant thoracic CT and multimodality imaging
      manifestations. CONCLUSION: Many breast cancer patients undergo cross-sectional
      imaging at some point during or after treatment. Thoracic CT is an important
      modality performed for staging and surveillance. Thoracic CT examinations often
      show findings related to patients' surgical or adjuvant treatment. The
      postsurgical changes visible on thoracic CT may include those related to
      lumpectomy, mastectomy, breast reconstruction, and axillary surgery. Postsurgical
      complications may also be seen, including fluid collections, infection, fat
      necrosis, and lymphedema. Recognition and appropriate interpretation of the
      posttherapeutic spectrum of findings are important to avoid unnecessary
      diagnostic imaging and minimize patient anxiety.

PMID- 24450665
TI  - Diagnostic accuracy and recall rates for digital mammography and digital
      mammography combined with one-view and two-view tomosynthesis: results of an
      enriched reader study.
AB  - OBJECTIVE: The purpose of this study was to compare two methods of combining
      tomosynthesis with digital mammography by assessing diagnostic accuracy and
      recall rates for digital mammography alone and digital mammography combined with
      one-view tomosynthesis and two-view tomosynthesis. SUBJECTS AND METHODS: Three
      hundred ten cases including biopsy-proven malignancies (51), biopsy-proven benign
      findings (47), recalled screening cases (138), and negative screening cases (74)
      were reviewed by 15 radiologists sequentially using digital mammography, adding
      one-view tomosynthesis, and then two-view tomosynthesis. Cases were assessed for
      recall and assigned a BI-RADS score and probability of malignancy for each
      imaging method. Diagnostic accuracy was assessed using receiver operating
      characteristic (ROC) analysis. Screening recall rates were compared using pooled
      logistical regression analysis. A p value of < 0.0167 was considered significant.
      RESULTS: The area under the ROC curve (AUC) for digital mammography (DM), DM plus
      one-view tomosynthesis, and DM plus two-view tomosynthesis was 0.828, 0.864, and
      0.895, respectively. Both one-view and two-view tomosynthesis plus DM were
      significantly better than DM alone (Delta AUCs 0.036 [p = 0.009] and 0.068 [p <
      0.001]). Average noncancer recall rates for digital mammography, DM plus one-view
      tomosynthesis, and DM plus two-view tomosynthesis were 44.2%, 27.2%, and 24.0%,
      respectively. Combined with DM, one-view and two-view tomosynthesis both showed
      significantly lower noncancer recall rates than digital mammography alone (p <
      0.001). Digital mammography with two-view tomosynthesis showed a significantly
      lower recall rate than digital mammography with one-view tomosynthesis (p <
      0.001). Diagnostic accuracy for dense (Delta AUC, 0.091%; p < 0.001) and nondense
      (Delta AUC, 0.035%; p = 0.001) breasts improved with DM plus two-view
      tomosynthesis compared with digital mammography alone. Compared with digital
      mammography, diagnostic sensitivity for invasive cancers increased with the
      addition of both one-view (Delta12.0%, p < 0.001) and two-view (Delta21.7%, p <
      0.001) tomosynthesis. CONCLUSION: The addition of one-view tomosynthesis to
      conventional digital mammography improved diagnostic accuracy and reduced the
      recall rate; however, the addition of two-view tomosynthesis provided twice the
      performance gain in diagnostic accuracy while further reducing the recall rate.

PMID- 24450667
TI  - Importance of a personal history of breast cancer as a risk factor for the
      development of subsequent breast cancer: results from screening breast MRI.
AB  - OBJECTIVE: The purposes of this study were to assess the importance of a personal
      history of breast cancer as a risk factor for patients referred for screening
      breast MRI and to evaluate the importance of this risk factor compared with
      family history. MATERIALS AND METHODS: A retrospective review of screening breast
      MRI performed from 2004 to 2012 included a total of 702 patients, 465 of whom had
      undergone annual MRI and 237 of whom had undergone MRI every 6 months as part of
      a research protocol. RESULTS: Of the patients screened, 208 had a personal
      history of breast cancer, and 345 had a family history as the sole risk factor.
      An additional 97 patients had both risk factors. The absolute risk for detection
      of breast cancer at screening MRI among patients with a personal history of
      cancer was 2.8% (95% CI, 0.6-5.2%). The absolute risk for patients with a strong
      family history of cancer was 2.0% (95% CI, 0.5-3.5%). The relative risk for
      detection of breast cancer given a personal history was 1.42 (95% CI, 0.48-4.17)
      compared with family history. The relative risk when both risk factors were
      present compared with having only a family history was 3.04 (95% CI, 1.05-8.86).
      CONCLUSION: A personal history of breast cancer is an important risk factor for
      the development of subsequent breast cancer. Given the results, consideration
      should be given to MRI screening of patients with a personal history of breast
      cancer.

PMID- 24450666
TI  - Neglecting to screen women between 40 and 49 years old with mammography: what is
      the impact on treatment morbidity and potential risk reduction?
AB  - OBJECTIVE: The purpose of this study is to determine whether there were
      significant differences with respect to treatment recommendations, stage at
      diagnosis, and identification of high-risk lesions for women 40-49 years old
      undergoing screening mammography (screened) compared to women with a symptom
      needing a diagnostic evaluation (nonscreened). MATERIALS AND METHODS: We reviewed
      the pathology results of all imaging-guided biopsies performed at the three
      breast center locations of University Hospitals Case Medical Center from January
      1, 2008, to December 31, 2011. In patients diagnosed with a high-risk lesion or
      breast cancer, the reason for presentation, pathology, tumor size, stage,
      receptor characteristics, and treatment were recorded. The chi-square test was
      used for statistical analysis. RESULTS: Of 230 primary breast cancers, 149 were
      in the screened group and 81 were considered nonscreened. Nonscreened patients
      were more likely to undergo chemotherapy (p = 0.042). Eighty-one percent of the
      high-risk lesions were diagnosed in the screened patients. Screened patients with
      cancer were significantly more likely to receive a diagnosis at earlier stages (p
      = 0.001), to have negative axillary lymph nodes (p = 0.005), and to have smaller
      tumors (p < 0.001). CONCLUSION: In addition to the benefits of receiving a
      diagnosis at earlier stages, with smaller tumors and node negativity, patients
      with breast cancer undergoing screening mammography aged 40-49 years are less
      likely to require chemotherapy and its associated morbidities. The majority of
      high-risk lesions were diagnosed in the screened group, which may lead to the
      benefit of chemoprevention, lowering their risk of subsequent breast cancer, or
      screening with MRI, which may diagnose future mammographically occult
      malignancies.

PMID- 24450668
TI  - Breast-specific gamma imaging for the detection of breast cancer in dense versus
      nondense breasts.
AB  - OBJECTIVE: The purpose of this study was to evaluate the sensitivity of breast
      specific gamma imaging (BSGI) for the detection of breast cancer in dense versus
      nondense breasts. MATERIALS AND METHODS: This was a retrospective study of 341
      women with biopsy-proven breast cancer diagnosed from January 2004 to August 2009
      who underwent BSGI before surgical excision. Patients with predominantly fatty
      replaced (BI-RADS density 1) or scattered fibroglandular tissue (BI-RADS density
      2) breasts were classified as nondense, and those with heterogeneously dense (BI
      RADS density 3) or extremely dense tissue (BIRADS density 4) were classified as
      dense. BSGI examinations exhibiting focal increased radiotracer uptake in the
      area of biopsy-proven cancer were classified as positive according to BSGI
      reports in the medical record. The sensitivity of BSGI was calculated using
      Microsoft Excel 2003. Between-group differences were evaluated statistically
      using the Student t test for continuous variables and the chi-square test for
      categoric variables, with p < 0.05 considered statistically significant. RESULTS:
      The overall sensitivity of BSGI for breast cancer detection was 95.4%. Positive
      BSGI examinations were present in 136 of 142 nondense breast cancers and 195 of
      205 dense breast cancers, for sensitivities of 95.8% and 95.1%, respectively.
      There was no significant difference in BSGI breast cancer detection and
      parenchymal breast density (p = 0.459). CONCLUSION: BSGI has high sensitivities
      for the detection of breast cancer in women with dense and nondense breasts and
      is an effective adjunct imaging modality in women with both dense and nondense
      breasts.

PMID- 24450669
TI  - Digital breast tomosynthesis from concept to clinical care.
AB  - OBJECTIVE: The purpose of this article is to describe the development of digital
      breast tomosynthesis (DBT) and to describe its advantages over 2D mammography for
      breast cancer screening. CONCLUSION: Mammographic screening has dramatically
      reduced breast cancer deaths, but it does not depict all cancer early enough to
      result in a cure. In addition, because of the recall rates associated with
      mammography, efforts are underway to reduce access to screening. Use of DBT
      improves sensitivity and specificity, and there is no longer a need to obtain
      full-exposure 2D mammograms. DBT will replace standard 2D mammography for breast
      cancer screening.

PMID- 24450670
TI  - Xenon-enhanced dual-energy CT lung ventilation imaging: techniques and clinical
      applications.
AB  - OBJECTIVE: The purpose of this article is to review the techniques, clinically
      relevant potential applications, and limitations of xenon-enhanced dual-energy CT
      of the chest. CONCLUSION: The functional evaluation of lung ventilation may be of
      great importance to patients with pulmonary disease. Many measures are used to
      assess pulmonary function, but the results are estimates of only global status
      rather than the regional distribution of disease. With the introduction of dual
      energy CT, regional lung ventilation function can be assessed with inhaled xenon
      gas. This technique yields not only high-spatial-resolution anatomic information
      but also information about regional ventilation.

PMID- 24450671
TI  - Patient-tailored scan delay for multiphase liver CT: improved scan quality and
      lesion conspicuity with a novel timing bolus method.
AB  - OBJECTIVE: The purpose of this study was to compare scan quality and lesion
      conspicuity for late arterial and portal venous phase liver CT scans using fixed
      versus patient-tailored scan delay derived with an evidence-based timing bolus
      method. MATERIALS AND METHODS: We retrospectively identified the cases of 73
      patients who underwent both multiphase liver CT with fixed late arterial and
      portal venous phase scan delay times of 45 and 80 seconds and subsequent
      multiphase liver CT with patient-tailored scan delay determined with a timing
      bolus and a previously reported relation between the time to peak aortic and
      liver enhancement. Both late arterial and portal venous phase scans were graded
      in terms of scan quality. Hepatic lesion conspicuity (difference in attenuation
      between lesion and liver parenchyma) for hypervascular lesions (late arterial
      phase) and hypovascular lesions (portal venous phase) was recorded. RESULTS:
      Patient-tailored scan delay reflected a wide range of times to peak aortic
      enhancement (mean, 24 seconds; range, 18-32 seconds) and yielded a greater
      proportion of optimal scans compared with fixed scan delay for both late arterial
      phase (92% versus 74%, p < 0.01) and portal venous phase (86% versus 70%, p <
      0.05) scans. Mean hypervascular lesion conspicuity was greater for lesions imaged
      with patient-tailored scan delay rather than fixed scan delay (84.0 versus 57.0
      HU, p < 0.01). CONCLUSION: Compared with examinations with fixed scan delay,
      multiphase liver CT that incorporates patient-tailored scan delay produces more
      optimally timed late arterial and portal venous phase CT scans with greater
      lesion conspicuity.

PMID- 24450672
TI  - Diffusion-weighted MRI of the testes in patients with varicocele: a preliminary
      study.
AB  - OBJECTIVE: This preliminary study aimed to evaluate changes in apparent diffusion
      coefficient (ADC) values of the testes in patients presenting with varicocele.
      SUBJECTS AND METHODS: This cross-sectional study included 25 consecutively
      recruited patients with varicocele and 25 healthy control volunteers. The ADC
      values were measured in all participants. Kolmogorov-Smirnov tests were used to
      test the normality of the data distributions, and the data were expressed as
      arithmetic means and SDs. A one-way analysis of variance with a post hoc
      Bonferroni test was used to analyze normally distributed continuous data.
      Independent sample Student t tests were used to compare continuous variables
      between two groups. Furthermore, a Pearson correlation coefficient analysis was
      used to examine the association of venous diameters with mean ADC values in
      patients with varicocele. A two-sided p value < 0.05 was considered statistically
      significant. Sensitivities, specificities, and areas under the curve were
      calculated for the ADC values. RESULTS: The ADC values associated with the
      ipsilateral testicular parenchyma of patients with varicocele were found to be
      lower than those of healthy volunteers. Moreover, the ADC values of the
      contralateral testicular parenchyma in patients with varicocele were also lower
      than those of healthy volunteers. The sensitivity and specificity of ADC values
      were 90% and 96%, respectively, for patients with varicocele and 89.5% and 96%
      for healthy volunteers. The mean ADC values were significantly negatively
      correlated with venous diameter. CONCLUSION: The measurement of testicular ADC
      values may be used as a diagnostic indicator in the detection of testicular
      fibrosis.

PMID- 24450673
TI  - Delayed imaging in routine CT examinations of the abdomen and pelvis: is it worth
      the additional cost of radiation and time?
AB  - OBJECTIVE: The purpose of this study was to retrospectively assess the potential
      benefits of delayed phase imaging series in routine CT scans of the abdomen and
      pelvis. MATERIALS AND METHODS: Routine contrast-enhanced abdominopelvic CT scans
      of 1000 consecutively examined patients (912 men, 88 women; average age, 60
      years; range, 22-94 years) were retrospectively evaluated, and the added benefits
      of the delayed phase series through the abdomen were recorded for each
      examination. Examinations performed for indications requiring multiphasic imaging
      were excluded. Images were reviewed by two fellowship-trained abdominal
      radiologists, who were blinded to official CT reports. All examinations were
      performed between July 2008 and February 2010 at a single institution. Radiation
      doses for both the portal venous and delayed phases, when available, were
      analyzed to assess the effect of the delayed phase on overall radiation exposure.
      RESULTS: Forty-two patients (4.2%) had findings that were further characterized
      or were observed only in the delayed phase. Most were incidental findings that
      could have been confirmed at noninvasive follow-up imaging, such as sonography or
      unenhanced CT or MRI. The most common findings were liver hemangioma (n = 12),
      adrenal adenoma (n = 12), and parapelvic renal cysts (n = 6). The most important
      finding was detection of a renal mass in one patient (0.1%). The mass was seen
      only on the delayed phase images but was difficult to appreciate in the portal
      venous phase. In the other 958 patients (95.8%), delayed imaging was of no
      benefit. In addition, use of the delayed phase resulted in a mean 59.5% increase
      in effective radiation dose. CONCLUSION: An additional delayed phase through the
      abdomen in routine contrast-enhanced CT examinations of the abdomen and pelvis is
      of low yield, particularly if reliable follow-up imaging to further elucidate
      uncertain findings is available.

PMID- 24450674
TI  - In vivo predictors of renal cyst pseudoenhancement at 120 kVp.
AB  - OBJECTIVE: The purpose of this article is to assess the effects of various CT,
      patient, and renal cyst characteristics on the occurrence of pseudoenhancement in
      in vivo renal mass CT examinations using subtraction MRI as the reference
      standard. MATERIALS AND METHODS: Adult patients imaged with 120-kVp standard
      kernel biphasic renal mass protocol CT and dynamic contrast-enhanced MRI of the
      abdomen from January 1, 2005, through May 4, 2012, were identified. Those with
      nonenhancing Bosniak categories I and II cysts on MRI were selected (n = 33
      patients; 110 cysts). By treating measured cyst enhancement (nephrographic CT
      attenuation minus unenhanced CT attenuation) as either a continuous or categoric
      outcome variable, a variety of CT, patient-level, and renal cyst characteristics
      were assessed using mixed effect multivariate models. RESULTS: On univariate
      assessment, cysts that exhibited pseudoenhancement (> 10 HU) were significantly
      more endophytic (p = 0.02), significantly smaller (p = 0.0004), and adjacent to
      significantly higher attenuation renal parenchyma in the nephrographic phase (p =
      0.02). On multivariate assessment, cyst diameter (p < 0.0001) and background
      nephrographic phase parenchymal attenuation (p = 0.003) were the strongest in
      vivo predictors of pseudoenhancement. The odds of pseudoenhancement occurring
      increased by 2.14 (95% CI, 1.41-3.23) for every 5-mm decrease in renal cyst
      diameter and increased by 2.45 (95% CI, 1.41-4.26) for every 25-HU increase in
      enhanced renal parenchymal attenuation. Endophytic growth was not significant in
      the multivariate analyses (p = 0.07). CONCLUSION: Renal cyst size and enhanced
      renal parenchymal attenuation are better in vivo predictors of pseudoenhancement
      than is endophytic growth pattern.

PMID- 24450675
TI  - Accuracy of multiparametric MRI for prostate cancer detection: a meta-analysis.
AB  - OBJECTIVE: The purpose of this diagnostic meta-analysis was to determine the
      diagnostic accuracy of multiparametric MRI for prostate cancer detection using
      anatomic T2-weighted imaging combined with two functional techniques: diffusion
      weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND
      METHODS: We searched electronic databases, including MEDLINE, Embase, and the
      Cochrane Central Register of Controlled Trials (CENTRAL) up to February 3, 2012.
      We included diagnostic accuracy studies using a combination of T2-weighted
      imaging, DWI, and DCE-MRI to detect prostate cancer with histopathologic data
      from prostatectomy or biopsy as the reference standard. The methodologic quality
      was assessed with version 2 of the Quality Assessment of Diagnostic Accuracy
      Studies (QUADAS-2) tool by two independent reviewers. Sensitivity and specificity
      of all studies were calculated from 2 * 2 tables, and the results were plotted in
      a hierarchic summary receiver operating characteristic plot. RESULTS: Seven
      studies that met the inclusion criteria (526 patients) could be analyzed. The
      pooled data showed a specificity of 0.88 (95% CI, 0.82-0.92) and sensitivity of
      0.74 (95% CI, 0.66-0.81) for prostate cancer detection, with negative predictive
      values (NPVs) ranging from 0.65 to 0.94. Subgroup analyses showed no significant
      difference between the subgroups. CONCLUSION: The high specificity with variable
      but high NPVs and sensitivities implies a potential role for multiparametric MRI
      in detecting prostate cancer.

PMID- 24450676
TI  - Professionalism in radiology: ideals and challenges.
AB  - OBJECTIVE: The Physician Charter defines the obligations of professionalism as
      being based on three fundamental principles and 10 professional commitments.
      Choices faced in the daily clinical practice of radiology may present as
      challenges because of conflicts between the ideals of professionalism and the
      realities of practice and personal interests of the physician. CONCLUSION: The
      true medical professional strikes a mindful balance that realizes a stimulating
      and fulfilling practice of medicine without compromise of patient care.

PMID- 24450677
TI  - The Choosing Wisely initiative of the American Board of Internal Medicine
      Foundation: what will its impact be on radiology practice?
AB  - OBJECTIVE. The Choosing Wisely initiative is a large-scale effort to reduce the
      use of unnecessary tests and procedures, many of which involve imaging.
      CONCLUSION. By identifying specific tests and procedures that are often overused,
      unnecessary, inappropriate, or ineffective, Choosing Wisely places the onus on
      physicians to reduce their use. 

PMID- 24450678
TI  - The fisherman's cards: how to address past and future radiation exposures in
      clinical decision making.
AB  - OBJECTIVE. The purpose of this article is to describe how to address patients'
      past-and future potential-radiation exposures when making an imaging decision in
      a given situation. CONCLUSION. The Biologic Effects of Ionizing Radiation
      committee has endorsed a linear no-threshold model to explain the relationship
      between radiation exposure and cancer risk. This model implies that past and
      future potential exposures should not impact current decisions. We present an
      analogy that deconstructs these counterintuitive conclusions and facilitates
      translation of key radiation risk principles to practice. 

PMID- 24450679
TI  - Integrated circuit detector technology in abdominal CT: added value in obese
      patients.
AB  - OBJECTIVE: The purpose of this article was to assess the effect of an integrated
      circuit (IC) detector for abdominal CT on image quality. MATERIALS AND METHODS:
      In the first study part, an abdominal phantom was scanned with various extension
      rings using a CT scanner equipped with a conventional discrete circuit (DC)
      detector and on the same scanner with an IC detector (120 kVp, 150 effective mAs,
      and 75 effective mAs). In the second study part, 20 patients were included who
      underwent abdominal CT both with the IC detector and previously at similar
      protocol parameters (120 kVp tube current-time product and 150 reference mAs
      using automated tube current modulation) with the DC detector. Images were
      reconstructed with filtered back projection. RESULTS: Image quality in the
      phantom was higher for images acquired with the IC compared with the DC detector.
      There was a gradually increasing noise reduction with increasing phantom sizes,
      with the highest (37% in the largest phantom) at 75 effective mAs (p < 0.001). In
      patients, noise was overall significantly (p = 0.025) reduced by 6.4% using the
      IC detector. Similar to the phantom, there was a gradual increase in noise
      reduction to 7.9% in patients with a body mass index of 25 kg/m(2) or lower (p =
      0.008). Significant correlation was found in patients between noise and abdominal
      diameter in DC detector images (r = 0.604, p = 0.005), whereas no such
      correlation was found for the IC detector (r = 0.427, p = 0.060). CONCLUSION: Use
      of an IC detector in abdominal CT improves image quality and reduces image noise,
      particularly in overweight and obese patients. This noise reduction has the
      potential for dose reduction in abdominal CT.

PMID- 24450680
TI  - Acromioclavicular joint: the other joint in the shoulder.
AB  - OBJECTIVE: The purpose of this article is to provide a review of
      acromioclavicular joint anatomy, describe common pathologies at the joint, and
      present normal and abnormal postoperative imaging findings after surgical
      treatments. CONCLUSION: Knowledge of anatomy with related pathologies, orthopedic
      trends, imaging findings, and complications, is important in assessing the
      acromioclavicular joint.

PMID- 24450681
TI  - Tomosynthesis of the wrist and hand in patients with rheumatoid arthritis:
      comparison with radiography and MRI.
AB  - OBJECTIVE: The purpose of this article is to compare tomosynthesis with
      radiography and MRI of the wrist and hand for evaluating bone erosion in patients
      with rheumatoid arthritis (RA). MATERIALS AND METHODS: Twenty consecutive
      patients with an established diagnosis of RA and five control patients were
      included in this study. They underwent radiography, tomosynthesis, and MRI of the
      bilateral hand and wrist within a week. The mean total dose of radiography and
      tomosynthesis was 0.13 and 0.25 mGy, respectively. MRI evaluation was performed
      according to the Outcome Measures in Rheumatology Clinical Trials
      recommendations. Bone erosion on images from the three modalities was
      independently reviewed by two certificated radiologists with a 4-point scale (0,
      normal; 1, discrete erosion; 2, < 50% of the joint surface; and 3, >= 50% of the
      joint surface). RESULTS: The detection rates of bone erosion for radiography,
      tomosynthesis, and MRI were 26.5%, 36.1%, and 36.7%, respectively. Significantly
      more bone erosions were revealed with tomosynthesis and MRI than with radiography
      (p < 0.01). When MRI was used as the reference standard, the sensitivity,
      specificity, and accuracy were 68.1%, 97.5%, and 86.7%, respectively, for
      radiography and 94.8%, 97.8%, and 96.7%, respectively, for tomosynthesis.
      Interobserver agreement (kappa value) for bone erosion was good to excellent on
      tomosynthesis and MRI for all joints (0.65-1.00 and 0.68-1.00, respectively),
      whereas it was slight to fair on radiography for some carpal bones and bases of
      metacarpal bones (0.22-0.56). CONCLUSION: Tomosynthesis is superior to
      radiography and almost comparable to MRI for the detection of bone erosion in
      patients with RA.

PMID- 24450682
TI  - Incidence and predictive factors of inadequate fine-needle aspirates for
      BRAF(V600E) mutation analysis in thyroid nodules.
AB  - OBJECTIVE: BRAF(V600E) mutation (valine-to-glutamate substitution at residue 600
      of the B-type Raf kinase gene) analysis from thyroid aspirates is increasingly
      used as a prognostic or diagnostic marker. However, it is limited under some
      conditions. The purpose of this study was to assess the incidence and predictive
      factors of thyroid nodules with specimens inadequate for BRAF(V600E) mutation
      analysis. MATERIALS AND METHODS: We performed a retrospective cohort study of
      consecutive patients who underwent ultrasound-guided fine-needle aspiration (FNA)
      and molecular testing of aspiration specimens. Patients who had inadequate
      specimens in both allele-specific polymerase chain reaction and direct DNA
      sequencing methods were selected. Univariate and multivariate logistic regression
      analyses were performed to identify predictive factors of specimens inadequate
      for molecular tests. RESULTS: Specimens inadequate for BRAF(V600E) mutation
      analysis were seen in 168 of 7001 (2.4%) patients. Factors, including patient age
      and sex, nodule size, ultrasound diagnosis, the presence of calcification, and
      cystic changes within thyroid nodules, were not significant predictors of
      inadequate mutation analysis. Oval-to-round or irregular shapes (e.g., not taller
      than-wide) and final benign results were significant factors in univariate
      analysis (p = 0.0002 and p = 0.0013, respectively). However, nodules aspirated by
      operators with less than 1 year of experience (odds ratio [OR], 3.005; p =
      0.0070), and those that had spiculated margins (OR, 6.139; p = 0.0142),
      isoechogenicity (OR, 10.374; p = 0.0442), or nondiagnostic cytologic findings
      (OR, 73.637; p = 0.0055) remained significant risk factors after adjustment in
      multivariable analysis. CONCLUSION: Thyroid nodule specimens inadequate for
      BRAF(V600E) mutation analysis were frequently associated with FNA aspiration
      performed by inexperienced operators, nondiagnostic cytologic findings, benign
      nodules on final diagnosis, and probably benign ultrasound findings, such as
      isoechogenicity and not-taller-than-wide shape.

PMID- 24450683
TI  - Assessment of MRI issues at 7 T for 28 implants and other objects.
AB  - OBJECTIVE: Metallic implants are currently a contraindication for volunteer
      subjects and patients referred for 7-T examinations because of concerns related
      to magnetic field interactions and MRI-related heating. Artifacts may also be
      problematic. Therefore, the purpose of this investigation was to evaluate these
      MRI issues for 28 implants and other objects in association with a 7-T MR system.
      MATERIALS AND METHODS: Tests were performed at 7 T using standardized procedures
      to evaluate magnetic field interactions (translational attraction and torque) for
      all 28 items. MRI-related heating and artifacts were assessed using spin-echo and
      gradient-echo pulse sequences, respectively, for two aneurysm clips located
      within a transmit-receive head radiofrequency coil. RESULTS: Eight of the 28
      items showed magnetic field interactions at levels that could pose risks to human
      subjects. The two aneurysm clips exhibited heating, but the temperature rise did
      not exceed 1 degrees C. Artifacts were dependent on the material and dimensions
      of each aneurysm clip. CONCLUSION: These findings show that certain implants and
      objects may be acceptable for human subjects undergoing MRI examinations at 7 T,
      whereas others may involve possible risks. This information has important
      implications for individuals referred for MRI examinations at 7 T.

PMID- 24450684
TI  - Interreader agreement and variability of FDG PET volumetric parameters in human
      solid tumors.
AB  - OBJECTIVE: The purpose of this article is to evaluate the interreader agreement
      and variability of two (18)F-FDG PET parameters, metabolic tumor volume and total
      lesion glycolysis, in human solid tumors. MATERIALS AND METHODS: One hundred
      eleven patients (mean [+/- SD] age, 61.9 +/- 12.5 years) with baseline staging
      FDG PET/CT scans were included. Two readers independently read the scans and
      segmented metabolic tumor volume and total lesion glycolysis using two fixed
      thresholds, 40% and 50% of the lesion's maximum standardized uptake value
      (SUVmax). The impact of the lesion's FDG avidity and location on reader agreement
      and variability was established. Intraclass correlation coefficient (ICC),
      precision, and Bland-Altman analysis were used to evaluate agreement and
      variability. RESULTS: The ICCs for 40% and 50% SUVmax segmentations of metabolic
      tumor volume between the readers were 0.987 and 0.995, and the corresponding
      values for 40% and 50% SUVmax segmentations of total lesion glycolysis were 0.987
      and 0.986, respectively (p = 0.0001). The corresponding precisions were 0.5%,
      0.2%, 0.5%, and 0.5%, respectively. The mean biases between the readers for 40%
      and 50% SUVmax segmentations of metabolic tumor volume were -1.78 +/- 8.42 mL and
      -0.46 +/- 2.1 mL and for 40% and 50% SUVmax segmentations of total lesion
      glycolysis were -7.3 +/- 31.6 g and -2.97 +/- 12.86 g, respectively. Subgroup
      analysis showed better precision and lesser variability for 50% SUVmax
      segmentations of metabolic tumor volume and total lesion glycolysis in patients
      with the highest and lowest FDG-avid primary tumors. The precision was highest
      and variability was lowest for lung tumors. CONCLUSION: There is excellent
      interreader agreement for measurement of metabolic tumor volume and total lesion
      glycolysis with 40% and 50% SUVmax threshold segmentations in human solid tumors.

PMID- 24450685
TI  - Wrist and ankle MRI of patients with juvenile idiopathic arthritis:
      identification of unsuspected multicompartmental tenosynovitis and arthritis.
AB  - OBJECTIVE: The purpose of this study was to characterize the extent of joint and
      tendon involvement in patients with juvenile idiopathic arthritis referred for
      MRI of the wrist or ankle. MATERIALS AND METHODS: Forty-five patients (32 female
      and 13 male patients; mean age, 10 years; age range, 1-19 years) with an
      established diagnosis of juvenile idiopathic arthritis were referred for MRI of
      the wrist or ankle between January 2000 and August 2012 (39 wrists and 33
      ankles). All MRI examinations and clinical notes were reviewed, and joint and
      tendon involvement was recorded. RESULTS: Tenosynovitis was present in 50%
      (36/72) of examinations. Tenosynovitis was not documented in clinical notes
      before MRI. When tenosynovitis was present, an average of 3.5 tendons were
      involved (range, 1-12 tendons). For the wrist, 59% (23/39) had tenosynovitis, and
      the extensor digitorum tendon (23% [9/39]) was most commonly involved. For the
      ankle, 39% (13/33) had tenosynovitis, and the tibialis posterior tendon (33.3%
      [11/33]) was most commonly involved. For the wrist, 89.7% (35/39) had active
      joint inflammation with an average of 3.1 joints involved (range, 0-6 joints),
      and the intercarpal joint was most commonly involved (69% [27/39]). For the
      ankle, 69.7% (23/33) had active joint inflammation, with an average of 2.4 joints
      involved (range, 0-5 joints), and the tibiotalar joint (52% [17/33]) was most
      commonly involved. CONCLUSION: Multicompartmental tenosynovitis and arthritis
      involvement is common in patients with juvenile idiopathic arthritis referred for
      MRI of the wrist or ankle and is underappreciated on clinical examination.
      International League of Associations for Rheumatology subclassification and
      targeted intraarticular steroid injections guided by clinical examination alone
      may lead to undertreatment or incorrect treatment of active disease.

PMID- 24450686
TI  - Skeletal development of the proximal humerus in the pediatric population: MRI
      features.
AB  - OBJECTIVE: The purpose of this study was to provide a guideline of normal MRI
      developmental anatomy of the proximal humerus in a growing child. MATERIALS AND
      METHODS: Retrospective interpretation of 83 consecutive MRI studies of shoulders
      in children 2 months to 17 years old was performed in consensus by two
      radiologists. The following variables were documented: presence, number, and
      fusion of secondary ossification centers; appearance and closure of the growth
      plate; presence of the metaphyseal stripe; and proximal metaphyseal marrow signal
      intensity. RESULTS: Preossification centers were seen in 2- and 4-month-old
      patients. Secondary ossification centers appeared in the medial humeral head and
      greater tuberosity at 4 and 10 months, respectively, originally depicting red
      marrow and later converting to yellow marrow. A separate lesser tuberosity
      ossification center was not seen. The ossification centers began fusing by 3
      years and gradually conformed to the final shape of the proximal humerus.
      Ossification was completed by 13 years. The multilaminar growth plate initially
      had a flat and smooth contour that progressively became irregular and pyramidal,
      closing at 17 years. The metaphyseal stripe was noted at infancy and disappeared
      by 15.5 years. The metaphyseal marrow signal intensity was diffusely low in
      infants but, with conversion to yellow marrow, showed proximal metaphyseal bright
      patchy or linear signal-intensity, eventually disappearing by 17 years.
      CONCLUSION: The postnatal skeletal development of the proximal humerus in the
      pediatric population follows distinctive sequential patterns of maturation, which
      can serve as a guideline for interpreting MRI studies in children.

PMID- 24450687
TI  - Optimization of hybrid iterative reconstruction level in pediatric body CT.
AB  - OBJECTIVE: The objective of our study was to attempt to optimize the level of
      hybrid iterative reconstruction (HIR) in pediatric body CT. MATERIALS AND
      METHODS: One hundred consecutive chest or abdominal CT examinations were
      selected. For each examination, six series were obtained: one filtered back
      projection (FBP) and five HIR series (iDose(4)) levels 2-6. Two pediatric
      radiologists, blinded to noise measurements, independently chose the optimal HIR
      level and then rated series quality. We measured CT number (mean in Hounsfield
      units) and noise (SD in Hounsfield units) changes by placing regions of interest
      in the liver, muscles, subcutaneous fat, and aorta. A mixed-model analysis-of
      variance test was used to analyze correlation of noise reduction with the optimal
      HIR level compared with baseline FBP noise. RESULTS: One hundred CT examinations
      were performed of 88 patients (52 females and 36 males) with a mean age of 8.5
      years (range, 19 days-18 years); 12 patients had both chest and abdominal CT
      studies. Radiologists agreed to within one level of HIR in 92 of 100 studies. The
      mean quality rating was significantly higher for HIR than FBP (3.6 vs 3.3,
      respectively; p < 0.01). HIR caused minimal (0-0.2%) change in CT numbers. Noise
      reduction varied among structures and patients. Liver noise reduction positively
      correlated with baseline noise when the optimal HIR level was used (p < 0.01).
      HIR levels were significantly correlated with body weight and effective diameter
      of the upper abdomen (p < 0.01). CONCLUSION: HIR, such as iDose(4), improves the
      quality of body CT scans of pediatric patients by decreasing noise; HIR level 3
      or 4 is optimal for most studies. The optimal HIR level was less effective in
      reducing liver noise in children with lower baseline noise.

PMID- 24450688
TI  - Intussusception revisited: is immediate on-site surgeon availability at the time
      of reduction necessary?
AB  - OBJECTIVE: The American College of Radiology recommends that fluoroscopically
      guided intussusception reduction be performed with a surgeon readily available.
      At many institutions, this may not be feasible. The purpose of this study was to
      assess the utilization of immediate surgical services at the time of radiologic
      intussusception reduction. MATERIALS AND METHODS: All radiologic intussusception
      reductions at a tertiary care children's hospital from November 2007 through
      August 2012 were reviewed to determine method, complications, clinical status of
      the child, and time between unsuccessful reduction and operative intervention.
      RESULTS: Among 433 patients with intussusception referred for fluoroscopic
      reduction, 86.1% (n = 373) had successful reductions, and 13.9% (n = 60) had
      unsuccessful reductions. Five perforations represented 8.3% (5/60) of the
      unsuccessful and 1.2% (5/433) of the total reduction attempts. Six patients'
      conditions became hemodynamically unstable during attempted reduction (four
      perforations, two unsuccessful reductions without perforation), representing 10%
      (6/60) of unsuccessful and 1.4% (6/433) of total reduction attempts. Percutaneous
      needle decompression and cardiopulmonary resuscitation restored hemodynamic
      stability in all cases. The mean time to surgery after perforation was 1.3 hours,
      after unsuccessful reduction complicated by hemodynamic instability was 2.2
      hours, and after unsuccessful radiologic reduction without complication was 4.3
      hours. CONCLUSION: In this series, complications requiring immediate medical or
      surgical attention were rare, occurring in 1.6% of cases (five bowel
      perforations, two cases of hemodynamic instability without perforation). On-site
      surgeon presence may not be necessary at the time of radiologically guided
      reduction attempts provided that the attending physician is facile with
      percutaneous needle decompression and management of hemodynamic instability and
      that ultimate surgical care can be arranged expeditiously.

PMID- 24450689
TI  - Diameter measurement of vascular model on CT angiography using model-based
      iterative reconstruction: effect of tube current on accuracy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of tube current
      on the accuracy of vascular diameter measurements on CT angiography using model
      based iterative reconstruction (MBIR). MATERIALS AND METHODS: We constructed a
      physical phantom composed of nine vascular models of three wall thicknesses
      filled with contrast material of three densities and scanned the phantom using a
      64-MDCT unit with tube currents of 80, 40, 20, and 10 mA. We reconstructed raw
      data using MBIR and filtered back projection (FBP) algorithms and examined image
      sharpness by edge rise distance using four tube currents in each of the two
      reconstruction methods. We measured the mean inner diameter for each model for
      each set of image data using MBIR with the four tube currents (80, 40, 20, and 10
      mA) and FBP with tube current of 80 mA. RESULTS: Sharpness decreased as tube
      current decreased using MBIR (p < 0.0001) but did not differ significantly among
      the four tube currents using FBP (p = 0.0506). Sharpness using MBIR with 10 mA
      tube current was comparable to or significantly worse than that with FBP. The
      measurement error using MBIR tended to increase as tube current decreased. The
      measurement errors using MBIR with 10 mA tube current were comparable to or
      significantly larger than those using FBP for eight of the nine vascular models.
      CONCLUSION: By decreasing spatial resolution, MBIR with lower tube current can
      enhance errors in measurement of vascular diameter and should be applied
      carefully in evaluating vessel diameter.

PMID- 24450690
TI  - Techniques to expand patient selection for MRI-guided high-intensity focused
      ultrasound ablation of uterine fibroids.
AB  - OBJECTIVE: MRI-guided high-intensity focused ultrasound (HIFU) ablation is
      increasingly adopted for treating symptomatic uterine fibroids. As a noninvasive
      therapy performed on an outpatient basis, it has been viewed by patients to have
      distinct advantages over other treatment options. However, its breadth of
      clinical application is still limited. To address this issue, various techniques
      have been implemented. CONCLUSION: In this article, we discuss techniques that
      contribute to widening patient selection for MRI-guided HIFU therapy of uterine
      fibroids.

PMID- 24450691
TI  - Prediction of contrast-induced nephropathy in patients with serum creatinine
      levels in the upper normal range by cystatin C: a prospective study in 374
      patients.
AB  - OBJECTIVE: Preexisting renal impairment is a risk factor for contrast-induced
      nephropathy (CIN). In patients with creatinine in the upper normal level,
      cystatin C might be a more sensitive predictor of CIN than creatinine. Therefore,
      in this study, we investigated the usefulness of cystatin C to predict CIN.
      SUBJECTS AND METHODS: In 400 consecutive patients with creatinine baseline levels
      between 0.8 and 1.3 mg/dL undergoing coronary angiography (n = 200) or CT (n =
      200), baseline values of cystatin C, creatinine, blood urea nitrogen (BUN) and
      risk factors of CIN were determined. Creatinine was also assessed 24 and 48 hours
      after contrast administration. RESULTS: Creatinine significantly (p < 0.001)
      increased after 24 hours and 48 hours compared with baseline (1.06 +/- 0.28 and
      1.07 +/- 0.28 vs 0.99 +/- 0.18 mg/dL). Fifty-three of 373 evaluable patients
      (14.2%) had an increase in creatinine of >= 25% or >= 0.5 mg/dL within 48 hours.
      CIN according to this definition was significantly more frequent after
      intraarterial contrast administration (38/190, 20%) compared with IV contrast
      administration (15/183, 8.2%; p = 0.001). CIN was predicted by baseline cystatin
      C (area under the receiver operating characteristic [ROC] curve [AUC], 0.715; p <
      0.001), whereas creatinine, creatinine clearance, and BUN were not predictive.
      The best predictive capabilities were provided by cystatin C/creatinine-ratio
      (AUC, 0.826; p < 0.001). Multivariate regression analysis showed that
      intraarterial contrast administration (p = 0.002) and higher baseline cystatin C
      (p < 0.001) combined with low creatinine (p = 0.044) were independently
      associated with higher increases in creatinine within 48 hours after contrast
      administration. CONCLUSION: CIN in patients with creatinine within the upper
      normal range is significantly more frequent after intraarterial than after IV
      contrast administration. In these patients, renal impairment after contrast
      administration is independently predicted by cystatin C and cystatin C/creatinine
      ratio, whereas BUN and creatinine were not predictive.

PMID- 24450693
TI  - Spectrum of radiologic appearances of surgical thoracostomy and thoracoplasty in
      the treatment of pleuroparenchymal infections.

PMID- 24450694
TI  - Nonpuerperal mastitis and subareolar abscess of the breast.
AB  - OBJECTIVE: The purpose of this article is to show radiologists how to readily
      recognize nonpuerperal subareolar abscess and its complications in order to help
      reduce the time to definitive therapy and improve patient care. To achieve this
      purpose, the various theories of pathogenesis and the associated histopathologic
      features are reviewed; the typical clinical characteristics are detailed in
      contrast to those seen in lactational abscess and inflammatory breast cancer; the
      common imaging findings are described with emphasis on the sonographic features;
      correlative pathologic findings are presented to reinforce the imaging findings
      as they pertain to disease origins; and the various treatment options are
      reviewed. CONCLUSION: Nonpuerperal subareolar mastitis and abscess is a benign
      breast entity often associated with prolonged morbidity. Through better
      understanding of the underlying disease process the imaging, physical, and
      clinical findings of this rare process can be more readily recognized and
      treatment options expedited, improving patient care.

PMID- 24450695
TI  - Diaphragm disease of the small bowel: a retrospective review of CT findings.
AB  - OBJECTIVE: The purpose of this article is to report the CT findings of
      pathologically proven diaphragm disease in the small bowel. MATERIALS AND
      METHODS: A retrospective review identified 12 patients with pathologically proven
      small-bowel diaphragm disease who underwent CT within 6 months of surgical
      resection. Two radiologists, who were unblinded to pathologic and clinical
      findings, evaluated CT examinations for imaging findings of disease extent,
      appearance, and location. Clinical history and postoperative follow-up were also
      performed. RESULTS: The most common presenting symptoms were abdominal pain (7/12
      [58%]) and anemia (5/12 [42%]). Long-term use of nonsteroidal antiinflammatory
      drugs was documented in 58% (7/12) of patients. The most common location of small
      bowel diaphragms was the ileum (8/12 [67%]). The CT findings were abnormal in 92%
      (11/12) of patients. The most common CT findings were small-bowel strictures
      (11/12 [92%]) and focal (median length, 1 cm) bowel wall thickening (8/12 [67%]).
      Other less common CT findings included mucosal hyperenhancement (6/12 [50%]),
      small-bowel dilatation (5/12 [42%]), and video capsule retention (6/9 [67%]).
      Postoperative follow-up in 11 patients found recurrent symptoms in four patients.
      CONCLUSION: Small-bowel diaphragm disease should be considered in patients with a
      history of long-term use of nonsteroidal antiinflammatory drugs, chronic
      abdominal pain, and anemia who present with CT findings of short, symmetric ileal
      strictures and focal bowel wall thickening.

PMID- 24450696
TI  - Hybrid iterative reconstruction technique for abdominal CT protocols in obese
      patients: assessment of image quality, radiation dose, and low-contrast
      detectability in a phantom.
AB  - OBJECTIVE: The purpose of this study was to assess the impact of a noise
      reduction technique on image quality, radiation dose, and low-contrast
      detectability in abdominal CT for obese patients. MATERIALS AND METHODS: A liver
      phantom with 12 different tumors was designed, and fat rings were added to mimic
      intermediately sized and large patients. The intermediate and large phantoms were
      scanned with our standard abdominal CT protocol (image noise level of 15 HU and
      filtered back projection [FBP]). The large phantom was scanned with five
      different noise levels (10, 12.5, 15, 17.5, and 20 HU). All datasets for the
      large phantom were reconstructed with FBP and the noise reduction technique. The
      image noise and the contrast-to-noise ratio (CNR) were assessed. Tumor detection
      was independently performed by three radiologists in a blinded fashion. RESULTS:
      The application of the noise reduction method to the large phantom decreased the
      measured image noise (range, -14.5% to -37.0%) and increased the CNR (range, 26.7
      70.6%) compared with FBP at the same noise level (p < 0.001). However, noise
      reduction was unable to improve the sensitivity for tumor detection in the large
      phantom compared with FBP at the same noise level (p > 0.05). Applying a noise
      level of 15 HU, the overall sensitivity for tumor detection in the intermediate
      and large phantoms with FBP measured 75.5% and 87.7% and the radiation doses
      measured 42.0 and 23.7 mGy, respectively. CONCLUSION: Although noise reduction
      significantly improved the quantitative image quality in simulated large patients
      undergoing abdominal CT compared with FBP, no improvement was observed for low
      contrast detectability.

PMID- 24450697
TI  - The value of adding (18)F-FDG PET/CT to adrenal protocol CT for characterizing
      adrenal metastasis (>= 10 mm) in oncologic patients.
AB  - OBJECTIVE: The objective of our study was to evaluate the value that PET/CT adds
      to adrenal protocol CT for characterizing adrenal metastasis in oncologic
      patients. MATERIALS AND METHODS: Sixty-eight oncologic patients with 68 adrenal
      masses underwent both adrenal protocol CT and (18)F-FDG PET/CT. For adrenal
      protocol CT, metastasis was diagnosed if a mass measured more than 10 HU on
      unenhanced CT and if the absolute and relative percentage washouts were less than
      60% and 40%, respectively. For PET/CT, metastasis was diagnosed if FDG uptake of
      the lesion was equal to or greater than that of the liver. Diagnostic accuracies
      were compared between these two imaging modalities. RESULTS: The accuracy of
      adrenal protocol CT and PET/CT for a metastatic lesion, defined as a lesion with
      FDG uptake equal to or higher than that of the liver, was 85.3% (58/68) and 76.5%
      (52/68), respectively. However, the accuracy of PET/CT increased to 89.7% (61/68)
      when a lesion with high FDG uptake alone was considered a metastatic lesion. When
      both adrenal protocol CT and PET/CT were positive for metastasis, the accuracy
      increased to 91.2% (62/68), but the sensitivity decreased to 70.6% (12/17).
      CONCLUSION: Adding PET/CT to adrenal protocol CT improves the accuracy for
      adrenal metastasis in oncologic patients when a lesion with high FDG uptake alone
      is considered metastasis.

PMID- 24450698
TI  - Assessment of lower limb length and alignment by biplanar linear radiography:
      comparison with supine CT and upright full-length radiography.
AB  - OBJECTIVE: The purpose of this article is to compare lower limb length and
      alignment measurements on supine CT, upright full-length radiography, and 3D
      models based on upright biplanar linear radiography. SUBJECTS AND METHODS: This
      study involved 51 consecutive patients (22 men and 29 women; mean age, 68.8
      years; range, 43-92 years) who were scheduled for total knee replacement. Lower
      limb length and alignment angle were measured on CT, upright full-length
      radiography, and 3D models based on biplanar linear radiography with standard and
      composed leg methods by two independent readers. Descriptive statistics of each
      modality were calculated. Measurements of different modalities were compared by
      paired Student t tests. Agreement between readers and modalities was assessed by
      Bland-Altman analyses. RESULTS: Mean (+/- SD) limb lengths were 783 +/- 56.1 mm
      (range, 639-927 mm), 785 +/- 53.0 mm (range, 655-924 mm), 780 +/- 55.4 mm (range,
      633-921 mm), and 783 +/- 55.9 mm (range, 636-924 mm) for CT, upright full-length
      radiography, and 3D models based on biplanar linear radiography standard and
      composed leg measurements, respectively. Mean alignment angles were 2.3 degrees 
      +/- 5.5 degrees  (range, -12 degrees  to 20 degrees ) for CT, 2.5 degrees  +/-
      6.7 degrees  (range, -17 degrees  to 18 degrees ) for upright full-length
      radiography, and 3.4 degrees  +/- 6.6 degrees  (range, -14 degrees  to 18 degrees
      ) for 3D models based on biplanar linear radiography. No significant differences
      among modalities for mean limb length were found when using composed leg
      measurements in biplanar linear radiography. Very small but significant mean
      differences in angle measurements were seen for CT (-1.1 degrees  +/- 2.5) and
      upright full-length radiography (-0.9 degrees  +/- 3.1) compared with biplanar
      linear radiography. Bland-Altman analyses showed no significant differences
      between readers, with the highest agreement for biplanar linear radiography
      length measurements. CONCLUSION: Measurements on 3D models based on upright
      biplanar linear radiographs allow lower limb length and alignment angle
      measurements that are interchangeable with supine CT scans and upright full
      length radiographs but with superior interreader agreement.

PMID- 24450699
TI  - Ultrasound of the thumb ulnar collateral ligament: technique and pathology.
AB  - OBJECTIVE: The ulnar collateral ligament (UCL) serves an important role in
      stabilizing the thumb metacarpophalangeal (MCP) joint. The adductor pollicis
      aponeurosis lies superficial to the UCL, and plays an important role in the
      pattern of injury and treatment of UCL tears. Ultrasound is a cost-effective and
      accurate method to evaluate the UCL, allowing dynamic imaging and contralateral
      comparison in the setting of acute injury. The purpose of this video article is
      to show the optimal technique for sonographic evaluation of the UCL. CONCLUSION:
      UCL tears are common injuries involving the base of the thumb, and correct
      diagnosis of a Stener lesion aids in timely surgical management. Performing
      ultrasound evaluation in the long axis with use of dynamic imaging allows
      excellent visualization of the UCL and adductor pollicis aponeurosis. With
      application of appropriate technique, ultrasound is highly accurate in diagnosing
      Stener lesions.

PMID- 24450700
TI  - Bone subtraction 3D CT venography for the evaluation of cerebral veins and venous
      sinuses: imaging techniques, normal variations, and pathologic findings.
AB  - OBJECTIVE: Varying anatomic characteristics and clinical and radiologic
      manifestations are diagnostic challenges in the evaluation of the cerebral vein
      and of venous sinus diseases. The purpose of this article is to introduce bone
      subtraction CT venography and review normal variations and diseases involving the
      cerebral veins and venous sinuses. CONCLUSION: Knowledge of the normal variations
      and pathologic findings will be helpful for the accurate diagnosis of diseases
      involving the cerebral venous system. Bone subtraction CT venography offers
      complete 3D visualization of the cerebral venous system and can be useful for the
      evaluation of the cerebral vein and venous sinus diseases.

PMID- 24450701
TI  - Accuracy of MDCT for detection and identification of carotid atherosclerotic
      plaque in a rabbit model.
AB  - OBJECTIVE: There is a need for a simple, rapid, and repeatable noninvasive
      imaging method to accurately assess carotid atherosclerotic plaque. The purpose
      of this study was to explore the utility of MDCT and carotid artery plaque
      analysis software for detecting and identifying atherosclerotic plaque in a
      rabbit model of carotid atherosclerosis. MATERIALS AND METHODS: Plaques from 14
      rabbits and cross-sectional carotid artery specimens were detected, stained, and
      analyzed. Contrast-enhanced MDCT with application of carotid plaque analysis
      software was performed. Bland-Altman difference plots were used to assess
      interclass and intraclass consistency in lipid percentage and fibrous percentage
      on CT images. RESULTS: A total of 76 of the 158 samples were true positive for
      plaque. On the basis of histopathologic examination of the samples, the accuracy,
      sensitivity, and specificity of CT for detecting plaque were 91.8%, 89.4%, and
      94.5%, and the accuracy, sensitivity, and specificity of the software for
      classifying lipid-rich plaques and fibrous plaques were 90.8%, 90.6%, and 90.9%.
      Repeated measurements by the same physician showed good repeatability, and
      measurements by two physicians independently showed good correlation. CONCLUSION:
      The results showed that MDCT can be used to detect carotid atherosclerotic plaque
      and that carotid plaque analysis software can be used to measure the content of
      plaque composition and determine the nature of plaque.

PMID- 24450702
TI  - Medicolegal-malpractice and ethical issues in radiology. Routine comparison
      radiography of the extremities: should it be ordered and if so, how should it be
      billed?

PMID- 24450704
TI  - Use of stable isotopes to identify dietary differences across subpopulations and
      sex for a free-ranging generalist herbivore.
AB  - Carbon and nitrogen isotopes in tissues can be used to understand plants consumed
      by various taxa, but can they provide additional information about consumers?
      Values of delta(13)C and delta(15)N were assessed from tissue of free-ranging elk
      (Cervus elaphus) occupying disparate habitats of mixed prairie-oak savannah that
      contained C3 agricultural crops in a C4-dominated landscape and in key plants
      consumed by elk. Muscle and hoof samples were collected from female and male elk
      in two subpopulations (forested land and grassland) from private land and one
      subpopulation from the Wichita Mountains Wildlife Refuge (refuge) in 2001-2006.
      Previous research identified differences between mean muscle delta(13)C and
      delta(15)N and mean hoof delta(13)C and delta(15)N indicating that isotopes
      differed between tissues of varying metabolic activity. Mean delta(13)C in hoof
      of elk on forested land and grassland were lower than hoof delta(13)C from elk in
      the refuge indicating greater long-term consumption of C3 plants by elk on
      forested land and grassland subpopulations. The delta(15)N in hoof was greater
      for elk outside the refuge than that for elk in the refuge. Interaction of sex
      and subpopulation only occurred for hoof delta(15)N suggesting that factors such
      as tissue type, sex, and habitat need to be considered to understand free-ranging
      ecology of generalist herbivores using stable isotopes. Availability of C3
      agricultural crops high in percent nitrogen on a nearly annual basis in a C4
      dominated landscape was likely driving differences in tissue delta(13)C and
      delta(15)N among subpopulations of free-ranging elk. An increase in tissue
      delta(15)N resulted from an increase in the consumption of higher delta(15)N in
      forage for sexes and subpopulations of a free-ranging ungulate in North America
      but delta(15)N should be further evaluated as an index of nutrition for
      subpopulations of generalist herbivores. 

PMID- 24450703
TI  - Impaired social decision making in patients with major depressive disorder.
AB  - BACKGROUND: Abnormal decision-making processes have been observed in patients
      with major depressive disorder (MDD). However, it is unresolved whether MDD
      patients show abnormalities in decision making in a social interaction context,
      in which decisions have actual influences on both the self-interests of the
      decision makers per se and those of their partners. METHODS: Using a well-studied
      ultimatum game (UG), which is frequently used to investigate social interaction
      behavior, we examined whether MDD can be associated with abnormalities in social
      decision-making behavior by comparing the acceptance rates of MDD patients (N =
      14) with those of normal controls (N = 19). RESULTS: The acceptance rates of the
      patients were lower than those of the normal controls. Additionally, unfair
      proposals were accepted at similar rates from computer partners and human
      partners in the MDD patients, unlike the acceptance rates in the normal controls,
      who were able to discriminatively treat unfair proposals from computer partners
      and human partners. CONCLUSIONS: Depressed patients show abnormal decision-making
      behavior in a social interaction context. Several possible explanations, such as
      increased sensitivity to fairness, negative emotional state and disturbed
      affective cognition, have been proposed to account for the abnormal social
      decision-making behavior in patients with MDD. This aberrant social decision
      making behavior may provide a new perspective in the search to find biomarkers
      for the diagnosis and prognosis of MDD.

PMID- 24450705
TI  - The complete mitochondrial genome of the Gray's grenadier anchovy Coilia grayii
      (Teleostei, Engraulidae).
AB  - In this paper, the complete mitochondrial DNA (mtDNA) sequence of Coilia grayii
      was determined. The mitochondrial genome was 16,851 bp in length, including 13
      protein-coding genes, 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and a
      non-coding control region as those found in other vertebrates, with the gene
      identical to that of typical vertebrates. The overall base composition of the
      heavy strand were 26.09% of A, 31.14% of T, 15.58% of C and 27.19% of G, with a
      slight AT bias of 57.23%. With the exception of ND6 and eight tRNA genes, all
      other mitochondrial genes were encoded on the heavy strand.

PMID- 24450706
TI  - High coverage of the complete mitochondrial genome of the rare Gray's beaked
      whale (Mesoplodon grayi) using Illumina next generation sequencing.
AB  - Using an Illumina platform, we shot-gun sequenced the complete mitochondrial
      genome of Gray's beaked whale (Mesoplodon grayi) to an average coverage of 152X.
      We performed a de novo assembly using SOAPdenovo2 and determined the total
      mitogenome length to be 16,347 bp. The nucleotide composition was asymmetric
      (33.3% A, 24.6% C, 12.6% G, 29.5% T) with an overall GC content of 37.2%. The
      gene organization was similar to that of other cetaceans with 13 protein-coding
      genes, 2 rRNAs (12S and 16S), 22 predicted tRNAs and 1 control region or D-loop.
      We found no evidence of heteroplasmy or nuclear copies of mitochondrial DNA in
      this individual. Beaked whales within the genus Mesoplodon are rarely seen at sea
      and their basic biology is poorly understood. These data will contribute to
      resolving the phylogeography and population ecology of this speciose group.

PMID- 24450707
TI  - Complete mitochondrial genome of black grouse (Lyrurus tetrix).
AB  - We sequenced the entire mitochondrial genome of Lyrurus tetrix for the first
      time. The mitogenome was 16,677 bp in length, encoded with a standard set of 13
      protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes plus a
      putative control region. Almost all genes were encoded on the H-strand except the
      ND6 and eight tRNA genes. All protein-coding genes initiated with ATG, except for
      COX1 and ND5 (GTG). An 18-bp-nucleotide deletion occurred in the ND6 of Lyrurus
      tetrix in contrast to other Galliformes. The total base composition of the
      mitogenome was 30.4% for A, 30.4% for C, 25.8% for T and 13.4% for G. These
      results provide basic information for phylogenetic analyses among Galliformes.

PMID- 24450708
TI  - Mitochondrial genome of the flat-lip gudgeon, Platysmacheilus exiguus (Teleostei,
      Cypriniformes).
AB  - The complete mitogenome of an endemic fish in China flat-lip gudgeon,
      Platysmacheilus exiguous, was determined using the polymerase chain reaction and
      directly sequenced with the primer walking method. The whole mitogenome was
      16,604 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA
      (tRNA) genes, 2 ribosomal RNA (rRNA) genes and 1 control region. It had the
      typical circular molecule structure of vertebrate's mitogenome. The whole base
      composition was estimated to be 30.77%A, 26.06%T, 26.64%C and 16.53%G with AT
      bias of 56.83%. The complete mitogenome of P. exiguus provides the fundamental
      data for conservation genetics study on this species.

PMID- 24450709
TI  - The complete mitochondrial genome of the Hynobius maoershanensis (Caudata:
      hynobiidae).
AB  - The Hynobius maoershanensis is a member of hynobiidae, endemic to Mountain Maoer
      in Guangxi province, China. It was first found and reported in 2006 and so far
      there is a little molecular research about it. The complete mitochondrial genome
      of H. maoershanensis has been obtained for the first time in this study. The
      circular genome (16,412 bp in length) consisted of 37 typical animal
      mitochondrial genes (13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal
      RNA genes) and 1 control region. Overall base composition of the complete
      mitochondrial DNA was 33% A, 32% T, 21% C, and 14% G with AT (65%).

PMID- 24450710
TI  - Complete mitochondrial genome sequence of the common bean anthracnose pathogen
      Colletotrichum lindemuthianum.
AB  - Colletotrichum lindemuthianum is the causal agent of anthracnose in common bean
      (Phaseolus vulgaris), one of the most limiting factors for this crop in South and
      Central America. In this work, the mitochondrial sequence of a Colombian isolate
      of C. lindemuthianum obtained from a common bean plant (var. Cargamanto) with
      anthracnose symptoms is presented. The mtDNA codes for 13 proteins of the
      respiratory chain, 1 ribosomal protein, 2 homing endonucleases, 2 ribosomal RNAs
      and 28 tRNAs. This is the first report of a complete mtDNA genome sequence from
      C. lindemuthianum. 

PMID- 24450711
TI  - Complete mitochondrial genomes of two brown frogs, Rana dybowskii and Rana cf.
      chensinensis (Anura: Ranidae).
AB  - We first determined complete mitochondrial genomes of Rana dybowskii and Rana cf.
      chensinensis (Anura: Ranidae). The mitogenomic lengths of R. dybowskii and R. cf.
      chensinensis were 18,864 and 18,808 bp, respectively. The two mitogenomes have
      similar gene compositions including 13 protein-coding genes, 22 tRNA genes, 2
      rRNA genes and a control region. Rana dybowskii and R. cf. chensinensis
      mitogenomes displayed same gene order arrangements and similar base compositions
      with an A + T bias. Mitogenomic data of the two species contributed to provide
      molecular marker for their conservative genetics and clarified their phylogenetic
      position under mitogenome-based phylogeny of the genus Rana.

PMID- 24450713
TI  - The complete mitochondrial genome of Humphaplotropis culaishanensis sp. nov.
      (Orthoptera: Acridoidea: Pamphagidae: Pamphaginae).
AB  - The complete mitochondrial genome of Humphaplotropis culaishanensis sp. nov.,
      which was collected from the Shandong Province of China, is reported here. It was
      15,659 bp in length and contained 72.3% AT. All Humphaplotropis culaishanensis
      protein-coding sequences started with a typical ATN codon, excluding cox1 and
      nad6. The usual termination codon (TAN) and incomplete stop codons (T, TA) were
      found from 13 protein-coding genes. All tRNA genes could be folded into the
      typical cloverleaf secondary structure, excluding trnS(AGN) which forms another
      structure. The sizes of the large and small ribosomal RNA genes were 1322 and 852
      bp, respectively. The AT content of the A+T-rich region was 81.3%.

PMID- 24450712
TI  - The complete mitochondrial DNA of the silky shark (Carcharhinus falciformis).
AB  - The silky shark mitogenome (GeneBank accession number KF801102) has a total
      length of 17,774 bp, the base composition of the genomes was as follows: A
      (31.36%), T (30.18%), C (25.27%) and G (13.17%), which demonstrated an A + T-rich
      feature (61.64%), similar to other elasmobranch mitogenomes. The mitochondrial
      genome contained 13 protein-coding genes and 23 tRNA genes. The tRNA genes ranged
      from 70 to 72 bp. The gene order was the same as in other vertebrates and
      teleosts.

PMID- 24450714
TI  - The complete mitochondrial genome of Gryllotalpa unispina Saussure, 1874
      (Orthoptera: Gryllotalpoidea: Gryllotalpidae).
AB  - The complete mitochondrial genome of Gryllotalpa unispina was 15,513 bp in length
      and contained 70.9% AT. All G. unispina protein-coding sequences except for the
      nad2 started with a typical ATN codon. The usual termination codons (TAA) and
      incomplete stop codons (T) were found from 13 protein-coding genes. All tRNA
      genes were folded into the typical cloverleaf secondary structure, except
      trnS(AGN) lacking the dihydrouridine arm. The sizes of the large and small
      ribosomal RNA genes were 1245 and 725 bp, respectively. The A + T-rich region was
      917 bp in length with 76.8%. The orientation and gene order of the G. unispina
      mitogenome were identical to the G. orientalis and G. pluvialis, there was no
      phenomenon of "DK rearrangement" which has been widely reported in Caelifera.

PMID- 24450715
TI  - The complete chloroplast genome sequence of the wild cucumber Cucumis hystrix
      Chakr. (Cucumis, cucurbitaceae).
AB  - The complete nucleotide sequence of the wild cucumber (C. hystrix Chakr.)
      chloroplast genome has been determined in this study. The genome was composed of
      155,031 bp containing a pair of inverted repeats (IRs) of 25,150 bp, which was
      separated by a large single-copy region of 86,564 bp and a small single-copy
      region of 18,166 bp. The chloroplast genome contained 130 known genes, including
      89 protein-coding genes, 8 ribosomal RNA genes (4 rRNA species) and 37 tRNA genes
      (30 tRNA species), with 18 of them located in the IR region. In these genes, 16
      contained 1 intron, and 2 genes and one ycf contained 2 introns.

PMID- 24450716
TI  - The complete mitochondrial genome of the hybrid of Megalobrama amblycephala (?) *
      Parabramis pekinesis (?).
AB  - The complete mitochondrial genome sequence of the hybrid of blunt snout bream
      (Megalobrama amblycephala) (?) * white Amur bream (Parabramis pekinesis) (?) (M *
      P) was determined using the PCR-based method for the first time. The total length
      of the mitogenome was 16,623 bp in accordance with blunt snout bream. It
      contained 37 genes (13 protein-coding genes, 22 transfer RNA genes and 2
      ribosomal RNA genes) and 2 main non-coding regions (the control region and the
      origin of the light strand replication). Compared with the complete mitochondrial
      genome of the parents, results showed the hybrid bream was consistent with a
      maternal inheritance; however, we also found a termination codon mutation in Cytb
      and a double-based site in 16S rRNA which was species-specific for the male
      parent P. pekinesis. The complete mitochondrial genome sequence of the M * P
      bream provided an important data set for further study in mitochondrial
      inheritance mechanism.

PMID- 24450717
TI  - New complete mitochondrial genome of the Odontobutis potamophila (Perciformes,
      Odontobutidae): genome description and phylogenetic performance.
AB  - A new complete sequence of mitochondrial genome of Odontobutis potamophila has
      been reported. It was 16,843 bp and consisted of 13 protein-coding genes, 22 tRNA
      genes, 2 rRNA genes and 1 control region. Except for 8 tRNA and ND6 genes, all
      other mitochondrial genes were encoded on the heavy strand. Phylogenetic
      comparison proved that ND4, ND5 and ND6 genes might be dependable "leading"
      indicators of lineage divergence in Odontobutis obscurus. Also, COII, ND5 and
      cytb genes are useful in examining intraspecific population genetic diversity.

PMID- 24450718
TI  - Complete mitogenome of Hemiculter leucisculus (Cyprinidae: Cultrinae).
AB  - The complete mitogenome was first determined for a minnow Hemiculter leucisculus
      in this study. It is 16,622 bp in length and has 13 protein-coding genes, 2 rRNA
      genes, 22 tRNA genes and 1 control region. Overall nucleotide base composition is
      30.4% A, 27.10% C, 17.10% G and 25.40% T. All the tRNA genes can fold into the
      typical clover-leaf secondary structures, except the tRNA-Ser2 which loses the
      dihydrouridine arm and is replaced with one 11 bp loop. The origin of light
      strand replication (OL) was found between the tRNA-Asn and tRNA-Cys genes while
      the termination associated sequence (TAS) and the conserved sequence blocks (CSB1
      3) were found in the control region.

PMID- 24450719
TI  - The complete mitochondrial genome sequence of the Daweishan Mini chicken.
AB  - Daweishan Mini chicken is a valuable chicken breed in China. In this study, the
      complete mitochondrial genome sequence of Daweishan Mini chicken using PCR
      amplification, sequencing and assembling has been obtained for the first time.
      The total length of the mitochondrial genome was 16,785 bp, with the base
      composition of 30.26% A, 23.73% T, 32.51% C, 13.51% G. It contained 37 genes (2
      ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes) and a major
      non-coding control region (D-loop region). The protein start codons are ATG,
      except for COX1 that begins with GTG. The complete mitochondrial genome sequence
      of Daweishan Mini chicken provides an important data set for further
      investigation on the phylogenetic relationships within Gallus gallus.

PMID- 24450720
TI  - Characterization of the complete mitochondrial genome of the Australian
      Heliothine moth, Australothis rubrescens (Lepidoptera: Noctuidae).
AB  - Australothis rubrescens is basal to the Helicoverpa lineage containing pests such
      as Helicoverpa armigera, H. assulta and H. gelotopoeon. An illumina library of
      DNA from A. rubrescens was constructed and shallow sequencing and assembly of the
      DNA was conducted. The complete mitochondrial genome was identified using
      similarity to the H. armigera mitochondrial genome. The mitochondrial genome of
      A. rubrescens is 15,382 bp in length. It contains 37 genes which are shared with
      the vast majority of animals: 13 protein-coding genes (PCGs), 2 ribosomal RNAs,
      22 transfer RNAs and a non-coding AT-rich region (Table 1). As found in other
      Lepidopterans, the arrangement of all tRNAs of the A. rubrescens is identical to
      most insects. The complete mitochondrial genome of A. rubrescens will be an
      important tool in understanding the evolutionary history of the Heliothine moths.

PMID- 24450721
TI  - Complete mitochondrial genome of burbot (Lota lota: family Gadidae) from Amur
      basin lineage, Northeastern China.
AB  - The mitochondrial genome was amplified in two large overlapping fragments by long
      PCR and one gap PCR. The complete Northeastern China burbot mitogenome sequence
      (KC844053) is 16,575 bp in length. Similar to most vertebrata, the mitogenome has
      a set of 37 genes: including 13 protein-coding, 22 tRNA and 2 rRNA genes. More
      than 98% nucleotide sequence was simil to the reported individual.

PMID- 24450722
TI  - Complete mitochondrial genome of the blacknose shark Carcharhinus acronotus
      (Elasmobranchii: Carcharhinidae).
AB  - The complete mitochondrial genome of the blacknose shark Carcharhinus acronotus
      has been determined in this work. It has a length of 16,719 bp and consisted of
      13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 control region. The
      gene composition and genome organization was similar to other vertebrates. This
      study represents part of an ongoing effort to obtain mitochondrial genome
      sequences for chondrichthyan species in order to better estimate their
      phylogenetic relationships.

PMID- 24450723
TI  - Mitochondrial genome of silver gudgeon, Squalidus argentatus (Teleostei,
      Cypriniformes).
AB  - In this paper, we first determined the complete mitochondrial genome sequence of
      Squalidus argentatus, which was 16,607 bp in size and the whole base composition
      was estimated to be 30.48% A, 25.45% T, 27.36% C, 16.72% G with AT bias of
      55.93%. The complete mitogenome comprised 13 protein-coding genes, 22 transfer
      RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and 1 control region, with the
      gene order and content identical to other vertebrate mitogenomes. The complete
      mitogenome of S. argentatus provides the valuable information for population
      genetics and phylogeography studies on this species.

PMID- 24450724
TI  - The complete mitochondrial genome of Belgium Malinois (Canis; Canidae).
AB  - In this study, the complete nucleotide sequence of Belgium Malinois mitochondrial
      genome was determined for the first time. Sequence analysis showed that the
      genome structure was in accordance with other dogs. It contained 22 tRNA genes, 2
      ribosomal RNA genes, 13 protein-coding genes and 1 control region (D-loop
      region). The base composition was A (31.7%), G (14.1%), C (25.5%) and T (28.7%),
      so the percentage of A and T (60.4%) was higher than that of G and C. The
      complete mitochondrial genome sequence of the Belgium Malinois will shed a new
      light on further dog breeds study. 

PMID- 24450725
TI  - The complete mitochondrial genome of Garrulax cineraceus (Aves, Passeriformes,
      Timaliidae).
AB  - The complete sequence of the mitochondrial DNA genome from Garrulax cineraceus
      was determined using the polymerase chain reaction method. The genome (17,800 bp
      in length) contained 37 genes (13 protein-coding genes, 2 rRNA genes and 22 tRNA
      genes) and 2 control regions (D-loop) at two different locations of mitogenome,
      which is similar to the typical mtDNA of vertebrates. All the protein-coding
      genes in G. cineraceus were distributed on the H-strand, except for the ND6
      subunit gene and eight tRNA genes which were encoded on the L-strand.

PMID- 24450726
TI  - The complete mitochondrial genome of the moon moth, Actias aliena (Lepidoptera:
      Saturniidae).
AB  - In this study, we describe the complete mitochondrial genome (mitogenome)
      sequence of the Actias aliena belonging to the lepidopteran family Saturniidae in
      terms of general genomic features and composition. The 15,243 bp long genome
      consisted of a typical set of genes (13 protein-coding genes, 2 rRNA genes and 22
      tRNA genes) and 1 major non-coding A+T-rich region. The A. aliena mitogenome
      harbored the gene order tRNA(Met), tRNA(Ile) and tRNA(Gln) between the A+T-rich
      region and ND2, as shown in most lepidopteran species. The COI gene possessed the
      CGA initiator, which is found in nearly all lepidopterans lacking a canonical ATN
      initiator. Twenty-one tRNAs formed the cloverleaf secondary structures but
      tRNA(Ser)(AGN) formed a simple loop in the DHU arm. The 328 bp long A+T-rich
      region, which was located between the S rRNA and tRNA(Met) genes, contained
      several Lepidoptera-specific sequences, such as the ATAGA motif, a poly-T
      stretch, an AT repeat, and a poly-A stretch, along with an unusual tRNA(Phe)-like
      structure.

PMID- 24450727
TI  - Comparison of digital planimetry and ruler technique to measure ABSSSI lesion
      sizes in the ESTABLISH-1 study.
AB  - BACKGROUND: In August 2010, the U.S. Food and Drug Administration issued draft
      guidelines for developing antibiotics for treating acute bacterial skin and skin
      structure infections (ABSSSI), with the outcome measure of such treatment relying
      primarily on the cessation of spread or on the decrease in size of skin lesions
      at 48-72 h after the initiation of such treatment. In 2012, the Foundation for
      the National Institutes of Health proposed an interim outcome measure defined as
      a reduction in lesion size by >=20% at a 48-72 h examination. These recent
      changes make it necessary to identify reliable methods for measuring the lesions
      in acute infections of the skin. METHODS: In the first study of the Efficacy and
      Safety of 6-day Oral Tedizolid in Acute Bacterial Skin and Skin Structure
      Infections vs. 10-day Oral Linezolid Therapy (ESTABLISH-1), the sizes of ABSSSI
      lesions were evaluated with the two methodologies of: (1) Digital planimetry (DP)
      of photographed lesions, and (2) a ruler technique (RT) with measurement of the
      longest head-to-toe length and greatest perpendicular width of lesions, to
      compare the respective response rates of lesions to the two antimicrobial
      regimens in the study. RESULTS: The RT method and DP showed similar percentages
      of subjects in which treatment stopped the spread of ABSSSI lesions (93.2% vs.
      94.2%, respectively) but showed less agreement for a reduction in lesion size, of
      >=20% (87.7% vs. 62.0%, respectively) across all categories of lesions
      (cellulitis/erysipelas, major cutaneous abscess, and acute wound infection) at 48
      72 h after the initiation of treatment. CONCLUSION: The results of the ESTABLISH
      1 study show that both the RT method and DP are consistent and reliable
      techniques for measuring the sizes of ABSSSI lesions. Ultimately, changes in
      lesion size, rather than the absolute value of lesion size, will be used to
      assess the outcomes of treatment for ABSSSI in clinical research.

PMID- 24450728
TI  - Survival in fully manifest multiple organ dysfunction syndrome.
AB  - BACKGROUND: Multiple organ dysfunction syndrome (MODS) is the leading cause of
      death in intensive care units throughout the world. Several composite clinical
      scores, such as the Multiple Organ Dysfunction (MOD) score and Sequential Organ
      Failure Assessment (SOFA) score, have been developed to assess the severity of
      critical illness and predict mortality. Survival in fully manifest MODS is nearly
      unprecedented. METHODS: Case report and review of the relevant literature. CASE
      REPORT: A 55-year-old male was admitted to the neurologic intensive care unit
      with left lateral medullary syndrome, and access for permanent enteral feeding
      was indicated. On day 7 of the patient's hospitalization an attempt was made to
      place a gastrostomy tube in the patient, but the procedure was aborted after
      unexplained intra-operative hemodynamic instability. Eight days later the patient
      developed florid MODS of unclear etiology. His daily MOD and SOFA scores peaked
      at 16 and 20, respectively, and his cumulative MOD and SOFA scores peaked at 19
      and 22, respectively, portending 100% mortality. Over the next 6 wks the patient
      gradually recovered nearly all organ function, until both his MOD and SOFA scores
      decreased to 1. He was discharged to a sub-acute rehabilitation facility.
      CONCLUSIONS: This patient is the oldest patient reported to have survived fully
      manifest MODS. Whereas scoring systems such as the MOD and SOFA systems can be
      useful tools, they have several limitations and their results must be interpreted
      with caution.

PMID- 24450729
TI  - Simultaneous sampling of indoor and outdoor airborne radioactivity after the
      Fukushima Daiichi nuclear power plant accident.
AB  - Several studies have estimated inhalation doses for the public because of the
      Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Most of them were based
      on measurement of radioactivity in outdoor air and included the assumption that
      people stayed outdoors all day. Although this assumption gives a conservative
      estimate, it is not realistic. The "air decontamination factor" (ratio of indoor
      to outdoor air radionuclide concentrations) was estimated from simultaneous
      sampling of radioactivity in both inside and outside air of one building. The
      building was a workplace and located at the National Institute of Radiological
      Sciences (NIRS) in Chiba Prefecture, Japan. Aerosol-associated radioactive
      materials in air were collected onto filters, and the filters were analyzed by
      gamma spectrometry at NIRS. The filter sampling was started on March 15, 2011 and
      was continued for more than 1 year. Several radionuclides, such as (131)I,
      (134)Cs, and (137)Cs were found by measuring the filters with a germanium
      detector. The air decontamination factor was around 0.64 for particulate (131)I
      and 0.58 for (137)Cs. These values could give implications for the ratio of
      indoor to outdoor radionuclide concentrations after the FDNPP accident for a
      similar type of building. 

PMID- 24450731
TI  - Site-specific fluorescence dynamics of alpha-synuclein fibrils using time
      resolved fluorescence studies: effect of familial Parkinson's disease-associated
      mutations.
AB  - alpha-Synuclein (alpha-Syn) aggregation is directly implicated in both the
      initiation and spreading of Parkinson's Diseases (PD) pathogenesis. Although the
      familial PD-associated mutations (A53T, E46K, and A30P) are known to affect the
      aggregation kinetics of alpha-Syn in vitro, their structural differences in
      resultant fibrils are largely unknown. In this report we studied the site
      specific dynamics of wild type (wt) alpha-Syn and its three PD mutant fibrils
      using time-resolved fluorescence intensity, anisotropy decay kinetics, and
      fluorescence quenching. Our data suggest that the N- and C-terminus are more
      flexible and exposed compared to the middle non-amyloid-beta component (NAC)
      region of wt and PD mutant alpha-Syn fibrils. Yet the N-terminus showed great
      conformational heterogeneity compared to the C-terminus for all these proteins.
      71 position of E46K showed more flexibility and solvent exposure compared to
      other alpha-Syns, whereas both E46K and A53T fibrils possess a more rigid C
      terminus compared to wt and A30P. The present data suggest that wt and PD mutant
      fibrils possess large differences in flexibility and solvent exposure at
      different positions, which may contribute to their different pathogenicity in PD.

PMID- 24450730
TI  - Heterogeneous population effects of an alcohol excise tax increase on sexually
      transmitted infections morbidity.
AB  - BACKGROUND AND AIMS: Alcohol taxes reduce population-level excessive alcohol use
      and alcohol-related morbidity and mortality, yet little is known about the
      distribution of the effects of alcohol taxation across race/ethnicity and age
      subgroups. We examined the race/ethnicity- and age group-specific effects of an
      excise alcohol tax increase on a common and routinely collected alcohol-related
      morbidity indicator, sexually transmitted infections. METHODS: We used an
      interrupted time series design to examine the effect of a 2009 alcohol tax
      increase in Illinois, USA on new cases of two common sexually transmitted
      infections (chlamydia and gonorrhea) reported to the US National Notifiable
      Disease Surveillance System from January 2003 to December 2011 (n = 108 repeated
      monthly observations). We estimated the effects of the tax increase on infection
      rates in the general population and within specific race/ethnicity and age
      subgroups using mixed models accounting for temporal trends and median income.
      RESULTS: Following the Illinois alcohol tax increase, state-wide rates of
      gonorrhea decreased 21% [95% confidence Interval (CI) = -25.7, -16.7] and
      chlamydia decreased 11% [95% CI = -17.8, -4.4], resulting in an estimated 3506
      fewer gonorrhea infections and 5844 fewer chlamydia infections annually. The null
      hypothesis of homogenous effects by race/ethnicity and age was rejected (P <
      0.0001). Significant reductions were observed among non-Hispanic blacks:
      gonorrhea rates decreased 25.6% (95% CI = -30.0, -21.0) and chlamydia rates
      decreased 14.7% (95% CI = -20.9, -8.0). Among non-Hispanics, point estimates
      suggest decreases were highest among 25-29-year-olds. CONCLUSIONS: Increased
      alcohol taxes appear to reduce sexually transmitted infections, especially among
      subpopulations with high disease burdens, such as non-Hispanic blacks.

PMID- 24450732
TI  - Nurses' self-confidence and attitudes in using the Glasgow Coma Scale: a primary
      study.
AB  - AIMS: The aim of this study was to examine nurses' self-confidence and attitudes
      towards the Glasgow Coma Scale (GCS). BACKGROUND: The GCS measures the depth and
      duration of impaired consciousness. However, there is an increasing evidence that
      problems are encountered in completing some aspects of the GCS. DESIGN: This
      descriptive correlational study recruited 114 Registered Nurses (RNs) in one
      acute care hospital in Singapore. METHODS: A set of questionnaires were given to
      the participants. The questionnaire had three parts, which collected data on
      demographics, attitudes and self-confidence. RESULTS: Data analysis showed the
      type of clinical discipline (B=0.19), seniority in nursing (Staff Grade) (B=0.28)
      and higher attitude scores towards the GCS (B=0.41) were significant factors
      determining a nurse's confidence in using the GCS. A longer length of time
      working in a Neuroscience setting (B=0.21) and higher self-confidence scores
      (B=0.41) were significant factors determining a nurse's attitude towards the GCS.
      CONCLUSION: To ensure patient safety, the GCS has to be performed accurately.
      This study has shown there are differences in attitudes and self-confidence in
      using the GCS between nurses of different demographics, and that there are a
      variety of factors influencing their attitudes and confidence. RELEVANCE TO
      CLINICAL PRACTICE: Mentoring and educational interventions are suggested in order
      to reduce safety risks resulting from lower proficiency in using the GCS.

PMID- 24450734
TI  - Maximum movement velocity of the upper limbs reflects maximum gait speed in
      community-dwelling adults aged older than 60 years.
AB  - AIM: A number of studies have shown that the maximum movement velocity of the
      lower limbs is a critical determinant of gait speed in elderly adults. However,
      it is still unclear whether gait speed is associated with the movement velocity
      of the lower limbs or the movement velocity itself. Therefore, we measured the
      movement velocity of upper limbs that would not have a direct effect on gait, and
      examined the relationship between the movement velocity and gait speed. METHODS:
      A total of 76 community-dwelling adults aged older than 60 years (mean age 73.3
      years) participated in the study. We measured the movement velocity of the upper
      limbs, maximum gait speed, quadriceps strength, trunk muscle endurance and
      skeletal muscle mass index. RESULTS: A significant correlation was found between
      the movement velocity of the upper limbs and maximum gait speed (r=0.47; P<0.01).
      In a stepwise multiple regression analysis using maximum gait speed as a
      dependent variable, age, movement velocity of the upper limbs, body mass index
      and quadriceps strength were selected as independent variables (R(2)=0.55,
      P<0.001). CONCLUSIONS: The movement velocity of the upper limbs is a significant
      determinant of maximum gait speed, suggesting that the ability to move any region
      rapidly might be a critical factor in maximum gait speed.

PMID- 24450735
TI  - Leaf anatomical and photosynthetic acclimation to cool temperature and high light
      in two winter versus two summer annuals.
AB  - Acclimation of foliar features to cool temperature and high light was
      characterized in winter (Spinacia oleracea L. cv. Giant Nobel; Arabidopsis
      thaliana (L.) Heynhold Col-0 and ecotypes from Sweden and Italy) versus summer
      (Helianthus annuus L. cv. Soraya; Cucurbita pepo L. cv. Italian Zucchini
      Romanesco) annuals. Significant relationships existed among leaf dry mass per
      area, photosynthesis, leaf thickness and palisade mesophyll thickness. While the
      acclimatory response of the summer annuals to cool temperature and/or high light
      levels was limited, the winter annuals increased the number of palisade cell
      layers, ranging from two layers under moderate light and warm temperature to
      between four and five layers under cool temperature and high light. A significant
      relationship was also found between palisade tissue thickness and either cross
      sectional area or number of phloem cells (each normalized by vein density) in
      minor veins among all four species and growth regimes. The two winter annuals,
      but not the summer annuals, thus exhibited acclimatory adjustments of minor vein
      phloem to cool temperature and/or high light, with more numerous and larger
      phloem cells and a higher maximal photosynthesis rate. The upregulation of
      photosynthesis in winter annuals in response to low growth temperature may thus
      depend on not only (1) a greater volume of photosynthesizing palisade tissue but
      also (2) leaf veins containing additional phloem cells and presumably capable of
      exporting a greater volume of sugars from the leaves to the rest of the plant. 

PMID- 24450736
TI  - Impact of pNIPAM microgel size on its ability to stabilize Pickering emulsions.
AB  - We study the influence of the particle size on the ability of poly(N
      isoprolylacrylamide) microgels to stabilize direct oil-in-water Pickering
      emulsions. The microgel size is varied from 250 to 760 nm, the cross-linking
      density being kept constant. The emulsion properties strongly depend on the
      stabilizer size: increasing the particle size induces an evolution from dispersed
      drops and fluid emulsions toward strongly adhesive drops and flocculated
      emulsions. In order to get insight into this dependency, we study how particles
      adsorb at the interface and we determine the extent of their deformation. We
      propose a correlation between microgel ability to deform and emulsion macroscopic
      behavior. Indeed, as the microgels size increases, their internal structure
      becomes more heterogeneous and so does the polymeric interfacial layer they form.
      The loss of a uniform dense layer favors bridging between neighboring drops,
      leading to flocculated and therefore less handleable emulsions. 

PMID- 24450737
TI  - The effects of intestinal microbial community structure on disease manifestation
      in IL-10-/- mice infected with Helicobacter hepaticus.
AB  - BACKGROUND: The aberrant inflammation that is the hallmark of the inflammatory
      bowel diseases (IBD) is associated with several factors, including changes in the
      intestinal microbiota. Here, we confirmed that an intestinal microbiota is needed
      for development of typhlocolitis in Helicobacter hepaticus infected IL-10-/-
      C57BL/6 mice, and investigated the role of the microbiota in modulating disease.
      RESULTS: We altered the murine microbiota by treatment with the antibiotics
      vancomycin or cefoperazone prior to H. hepaticus infection. Through surveys of
      the 16S rRNA encoding-gene, analyses of histology and changes in expression of
      host mediators, we correlated alterations in the microbiota with host responses.
      We found that resident microbes are essential for initiation of disease, as
      animals mono-associated with H. hepaticus did not develop colitis. Despite the
      requirement for an indigenous microbiota for the initiation of disease, the
      severity of disease was independent of antibiotic-induced changes in the
      microbial community structure. Despite differences in the expression of host
      inflammatory mediators associated with shifts in the microbiota, H. hepaticus
      infection led to similar histopathologic lesions in microbial communities exposed
      to either cefoperazone or vancomycin. CONCLUSION: In conclusion, we demonstrate
      that colitis due to H. hepaticus infection can be initiated and progress in the
      presence of several different microbial communities. Furthermore, H. hepaticus is
      the main driver of inflammation in this model, while the specific structure of
      the microbiota may modulate the host pathways that lead to chronic inflammation.

PMID- 24450739
TI  - The freedom to explore: examining the influence of independent mobility on
      weekday, weekend and after-school physical activity behaviour in children living
      in urban and inner-suburban neighbourhoods of varying socioeconomic status.
AB  - BACKGROUND: Children's independent mobility (CIM) is critical to healthy
      development in childhood. The physical layout and social characteristics of
      neighbourhoods can impact opportunities for CIM. While global evidence is
      mounting on CIM, to the authors' knowledge, Canadian data on CIM and related
      health outcomes (i.e., physical activity (PA) behaviour) are missing. The purpose
      of this study was to examine if CIM is related to multiple characteristics of
      accelerometry-measured PA behaviour (total PA, light PA, moderate-to-vigorous PA,
      time spent sedentary) and whether associations between CIM and PA behaviour
      systematically vary by place of residence, stratifying by gender and type of
      day/period (weekdays, after-school, weekend). METHODS: Participants were
      recruited through Project BEAT (Built Environment and Active Transport;
      http://www.beat.utoronto.ca). Children (n = 856) were stratified into four
      neighbourhood classifications based on the period of neighbourhood development
      (urban built environment (BE) (old BE) versus inner-suburban BE (new BE)) and
      socioeconomic status (SES; low SES and high SES). Physical activity was measured
      via accelerometry (ActiGraph GT1M). CIM was assessed via parental report and two
      categories were created (low CIM, n = 332; high CIM, n = 524). A series of two
      factor ANOVAs were used to determine gender-specific differences in PA for
      weekdays, weekend days and the after-school period, according to level of CIM,
      across four neighbourhood classifications. RESULTS: Children who were granted at
      least some independent mobility (high CIM) had more positive PA profiles across
      the school week, during the after-school period, and over the weekend; they were
      also less sedentary. The influence of CIM on PA behaviour was particularly
      salient during the after-school period. Associations of CIM with PA varied by
      gender, and also by neighbourhood classification. CIM seemed to matter more in
      urban neighbourhoods for boys and suburban neighbourhoods for girls. CONCLUSION:
      Our findings highlight the importance of independent mobility to multiple
      characteristics of children's PA behaviour across the week. Furthermore, they
      emphasize that independent mobility-activity relationships need to be considered
      by gender and the type of neighbourhood independent mobility is offered in.
      Future work will focus on developing a predictive model of CIM that could be used
      to inform decision-making around alleviating barriers to CIM.

PMID- 24450740
TI  - Dry-heating of lysozyme increases its activity against Escherichia coli
      membranes.
AB  - For food as well as for medical applications, there is a growing interest in
      novel and natural antimicrobial molecules. Lysozyme is a promising candidate for
      the development of such molecules. This protein is largely studied and known for
      its muramidase activity against Gram-positive bacteria, but it also shows
      antimicrobial activity against Gram-negative bacteria, especially when previously
      modified. In this study, the activity of dry-heated lysozyme (DH-L) against
      Escherichia coli has been investigated and compared to that of native lysozyme (N
      L). Whereas N-L only delays bacterial growth, DH-L causes an early-stage
      population decrease. The accompanying membrane permeabilization suggests that DH
      L induces either larger pores or more pores in the outer membrane as compared to
      N-L, as well as more ion channels in the inner membrane. The strong morphological
      modifications observed by optical microscopy and atomic force microscopy when E.
      coli cells are treated with DH-L are consistent with the suggested disturbances
      of membrane integrity. The higher hydrophobicity, surface activity, and positive
      charge induced by dry-heating could be responsible for the increased activity of
      DH-L on the E. coli membranes. 

PMID- 24450741
TI  - Detection of nosocomial Clostridium difficile infections with toxigenic strains
      despite negative toxin A and B testing on stool samples.
AB  - A two-step diagnostic algorithm is recommended to detect Clostridium difficile
      infections; however, samples are regularly found that are glutamate dehydrogenase
      (GDH) positive but stool toxin negative. In the present single-centre prospective
      study we focused on these 'difficult-to-interpret' samples and characterized them
      by anaerobic culture, toxigenic culture, slpA sequence typing and multiplex PCR
      (GenoType CDiff). The majority of stool toxin A and B-negative samples have been
      caused by toxigenic strains including ribotype 027. The multiplex PCR was faster
      and more sensitive compared with culture and allowed preliminary identification
      of hypervirulent strains in stool samples on the same day. 

PMID- 24450742
TI  - Remission of long-standing alopecia universalis after human immunodeficiency
      virus infection.

PMID- 24450743
TI  - Cytokine networking of innate immunity cells: a potential target of therapy.
AB  - Innate immune cells, particularly macrophages and epithelial cells, play a key
      role in multiple layers of immune responses. Alarmins and pro-inflammatory
      cytokines from the IL (interleukin)-1 and TNF (tumour necrosis factor) families
      initiate the cascade of events by inducing chemokine release from bystander cells
      and by the up-regulation of adhesion molecules required for transendothelial
      trafficking of immune cells. Furthermore, innate cytokines produced by dendritic
      cells, macrophages, epithelial cells and innate lymphoid cells seem to play a
      critical role in polarization of helper T-cell cytokine profiles into specific
      subsets of Th1/Th2/Th17 effector cells or regulatory T-cells. Lastly, the innate
      immune system down-regulates effector mechanisms and restores homoeostasis in
      injured tissue via cytokines from the IL-10 and TGF (transforming growth factor)
      families mainly released from macrophages, preferentially the M2 subset, which
      have a capacity to induce regulatory T-cells, inhibit the production of pro
      inflammatory cytokines and induce healing of the tissue by regulating
      extracellular matrix protein deposition and angiogenesis. Cytokines produced by
      innate immune cells represent an attractive target for therapeutic intervention,
      and multiple molecules are currently being tested clinically in patients with
      inflammatory bowel disease, rheumatoid arthritis, systemic diseases,
      autoinflammatory syndromes, fibrosing processes or malignancies. In addition to
      the already widely used blockers of TNFalpha and the tested inhibitors of IL-1
      and IL-6, multiple therapeutic molecules are currently in clinical trials
      targeting TNF-related molecules [APRIL (a proliferation-inducing ligand) and BAFF
      (B-cell-activating factor belonging to the TNF family)], chemokine receptors, IL
      17, TGFbeta and other cytokines. 

PMID- 24450744
TI  - Modulation of the action of insulin by angiotensin-(1-7).
AB  - The prevalence of Type 2 diabetes mellitus is predicted to increase dramatically
      over the coming years and the clinical implications and healthcare costs from
      this disease are overwhelming. In many cases, this pathological condition is
      linked to a cluster of metabolic disorders, such as obesity, systemic
      hypertension and dyslipidaemia, defined as the metabolic syndrome. Insulin
      resistance has been proposed as the key mediator of all of these features and
      contributes to the associated high cardiovascular morbidity and mortality.
      Although the molecular mechanisms behind insulin resistance are not completely
      understood, a negative cross-talk between AngII (angiotensin II) and the insulin
      signalling pathway has been the focus of great interest in the last decade.
      Indeed, substantial evidence has shown that anti-hypertensive drugs that block
      the RAS (renin-angiotensin system) may also act to prevent diabetes. Despite its
      long history, new components within the RAS continue to be discovered. Among
      them, Ang-(1-7) [angiotensin-(1-7)] has gained special attention as a counter
      regulatory hormone opposing many of the AngII-related deleterious effects.
      Specifically, we and others have demonstrated that Ang-(1-7) improves the action
      of insulin and opposes the negative effect that AngII exerts at this level. In
      the present review, we provide evidence showing that insulin and Ang-(1-7) share
      a common intracellular signalling pathway. We also address the molecular
      mechanisms behind the beneficial effects of Ang-(1-7) on AngII-mediated insulin
      resistance. Finally, we discuss potential therapeutic approaches leading to
      modulation of the ACE2 (angiotensin-converting enzyme 2)/Ang-(1-7)/Mas receptor
      axis as a very attractive strategy in the therapy of the metabolic syndrome and
      diabetes-associated diseases. 

PMID- 24450745
TI  - Transcriptomic profiling to identify genes involved in Fusarium mycotoxin
      Deoxynivalenol and Zearalenone tolerance in the mycoparasitic fungus Clonostachys
      rosea.
AB  - BACKGROUND: Clonostachys rosea strain IK726 is a mycoparasitic fungus capable of
      controlling mycotoxin-producing Fusarium species, including F. graminearum and F.
      culmorum, known to produce Zearalenone (ZEA) and Deoxynivalenol (DON). DON is a
      type B trichothecene known to interfere with protein synthesis in eukaryotes. ZEA
      is a estrogenic-mimicing mycotoxin that exhibits antifungal growth. C. rosea
      produces the enzyme zearalenone hydrolase (ZHD101), which degrades ZEA. However,
      the molecular basis of resistance to DON in C. rosea is not understood. We have
      exploited a genome-wide transcriptomic approach to identify genes induced by DON
      and ZEA in order to investigate the molecular basis of mycotoxin resistance C.
      rosea. RESULTS: We generated DON- and ZEA-induced cDNA libraries based on
      suppression subtractive hybridization. A total of 443 and 446 sequenced clones
      (corresponding to 58 and 65 genes) from the DON- and ZEA-induced library,
      respectively, were analysed. DON-induced transcripts represented genes encoding
      metabolic enzymes such as cytochrome P450, cytochrome c oxidase and stress
      response proteins. In contrast, transcripts encoding the ZEA-detoxifying enzyme
      ZHD101 and those encoding a number of ATP-Binding Cassette (ABC) transporter
      transcripts were highly frequent in the ZEA-induced library. Subsequent
      bioinformatics analysis predicted that all transcripts with similarity to ABC
      transporters could be ascribed to only 2 ABC transporters genes, and phylogenetic
      analysis of the predicted ABC transporters suggested that they belong to group G
      (pleiotropic drug transporters) of the fungal ABC transporter gene family. This
      is the first report suggesting involvement of ABC transporters in ZEA tolerance.
      Expression patterns of a selected set of DON- and ZEA-induced genes were
      validated by the use of quantitative RT-PCR after exposure to the toxins. The qRT
      PCR results obtained confirm the expression patterns suggested from the EST
      redundancy data. CONCLUSION: The present study identifies a number of transcripts
      encoding proteins that are potentially involved in conferring resistance to DON
      and ZEA in the mycoparasitic fungus C. rosea. Whilst metabolic readjustment is
      potentially the key to withstanding DON, the fungus produces ZHD101 to detoxify
      ZEA and ABC transporters to transport ZEA or its degradation products out from
      the fungal cell.

PMID- 24450746
TI  - Managing chronic pain in elderly patients requires a CHANGE of approach.
AB  - In many countries, the number of elderly people has increased rapidly in recent
      years and this is expected to continue; it has been predicted that almost a
      quarter of the population in the European Union will be over 65 years of age in
      2035. Many elderly people suffer from chronic pain but it is regularly under
      treated, partly because managing these patients is often complex. This paper
      outlines the extent of untreated pain in this population and the consequent
      reduction in quality of life, before articulating the reasons why it is poorly or
      inaccurately diagnosed. These include the patient's unwillingness to complain,
      atypical pain presentations, multiple morbidities and cognitive decline.
      Successful pain management depends upon accurate diagnosis, which is based upon a
      complete history and thorough physical examination, as well as an assessment of
      psychosocial functioning. Poor physician/patient communication can be improved by
      using standardized instruments to establish individual treatment targets and
      measure progress towards them. User-friendly observational instruments may be
      valuable for patients with dementia. In line with the widely accepted
      biopsychosocial model of pain, a multidisciplinary approach to pain management is
      recommended, with pharmacotherapy, psychological support, physical rehabilitation
      and interventional procedures available if required. Declining organ function and
      other physiological changes require lower initial doses of analgesics and less
      frequent dosing intervals, and the physician must be aware of all medications
      that the patient is taking, in order to avoid drug/drug interactions. Non
      adherence to treatment is common, and various strategies can be employed to
      improve it; involving the elderly patient's caregivers and family, using
      medication systems such as pill-boxes, or even sending text messages. In the long
      term, the teaching of pain medicine needs to be improved--particularly in the use
      of opioids--both at undergraduate level and after qualification.

PMID- 24450747
TI  - Biosynthesis, elicitation and roles of monocot terpenoid phytoalexins.
AB  - A long-standing goal in plant research is to optimize the protective function of
      biochemical agents that impede pest and pathogen attack. Nearly 40 years ago,
      pathogen-inducible diterpenoid production was described in rice, and these
      compounds were shown to function as antimicrobial phytoalexins. Using rice and
      maize as examples, we discuss recent advances in the discovery, biosynthesis,
      elicitation and functional characterization of monocot terpenoid phytoalexins.
      The recent expansion of known terpenoid phytoalexins now includes not only the
      labdane-related diterpenoid superfamily but also casbane-type diterpenoids and
      beta-macrocarpene-derived sequiterpenoids. Biochemical approaches have been used
      to pair pathway precursors and end products with cognate biosynthetic genes. The
      number of predicted terpenoid phytoalexins is expanding through advances in
      cereal genome annotation and terpene synthase characterization that likewise
      enable discoveries outside the Poaceae. At the cellular level, conclusive
      evidence now exists for multiple plant receptors of fungal-derived chitin
      elicitors, phosphorylation of membrane-associated signaling complexes, activation
      of mitogen-activated protein kinase, involvement of phytohormone signals, and the
      existence of transcription factors that mediate the expression of phytoalexin
      biosynthetic genes and subsequent accumulation of pathway end products. Elicited
      production of terpenoid phytoalexins exhibit additional biological functions,
      including root exudate-mediated allelopathy and insect antifeedant activity. Such
      findings have encouraged consideration of additional interactions that blur
      traditionally discrete phytoalexin classifications. The establishment of mutant
      collections and increasing ease of genetic transformation assists critical
      examination of further biological roles. Future research directions include
      examination of terpenoid phytoalexin precursors and end products as potential
      signals mediating plant physiological processes. 

PMID- 24450751
TI  - Infection control practices among intensive care unit registered nurses: a
      Jordanian national study.
AB  - AIMS: This study aimed to evaluate infection control (IC) practices among
      Jordanian registered nurses (RNs) working in intensive care unit (ICU) settings.
      BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends
      periodic assessment of IC practices for health care workers as an effective
      strategy to control infections. DESIGN: Cross-sectional descriptive design.
      METHODS: A stratified, cluster random sampling technique was used. The sample
      consisted of ICU RNs from all major health care service providers and from all
      geographical areas in Jordan. The IC-Practices Tool (Cronbach alpha = 0.88) a
      self-report instrument was used. RESULTS: A total of 21 hospitals participated in
      the study, of which, 8 were governmental, 7 military, 4 private and 2 university
      affiliated. The final sample consisted of 247 RNs from 56 critical care units. Of
      the total sample, 36% of RNs were from governmental hospitals. Of the total
      sample, 51% were female with a mean age of 28.5 years (SD = 5.2), and 54.7%
      worked in general ICUs. The mean overall IC practice score was 122.6 (SD = 13.2).
      Nurses who reported that they had been trained about IC procedures in their
      hospital scored higher on the IC practice scale (M = 124.3, SD = 12.3) than
      nurses who never received any IC training in the hospital (M = 117.3, SD = 14.6,
      p < 0.001). CONCLUSION: This study demonstrated the importance of conducting IC
      educational programmes as an effective strategy to increase staff compliance with
      standard IC practices. RELEVANCE TO CLINICAL PRACTICE: Educational role of IC
      nurse is important to enhance RNs compliance with standard IC practices.

PMID- 24450752
TI  - Fringe patterns generated by micro-optical sensors for pattern recognition.
AB  - We present a new result of pattern recognition generation scheme using a small
      scale optical muscle sensing system, which consisted of an optical add-drop
      filter incorporating two nonlinear optical side ring resonators. When light from
      laser source enters into the system, the device is stimulated by an external
      physical parameter that introduces a change in the phase of light propagation
      within the sensing device, which can be formed by the interference fringe
      patterns. Results obtained have shown that the fringe patterns can be used to
      form the relationship between signal patterns and fringe pattern recognitions. 

PMID- 24450753
TI  - Aligned bacterial PHBV nanofibrous conduit for peripheral nerve regeneration.
AB  - The conventional method of peripheral nerve gap treatment is autografting. This
      method is limited. In this study, an aligned nanofibrous graft was formed using
      microbial polyester, Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The
      regenerative effect of the graft was compared with that of autografting in vivo.
      To determine the regenerative effect, rats were assessed with sciatic nerve
      functional index, electromyographic evaluation, and histological evaluation.
      Results found in this study include PHBV grafts stimulated progressive nerve
      regeneration, although regeneration was not comparable with that of autografting.
      We conclude that the study results were promising for aligned bacterial polymeric
      grafts for peripheral nerve regeneration. 

PMID- 24450754
TI  - A population-based study of edentulism in the US: does depression and rural
      residency matter after controlling for potential confounders?
AB  - BACKGROUND: Oral health is an integral component of general health and well
      being. While edentulism has been examined in relation to socioeconomic status,
      rural residency, chronic disease and mental health, no study that we know of has
      examined edentulism and these factors together. The objective of this study was
      to determine whether depression and rural residency were significantly associated
      with partial and full edentulism in US adults after controlling for potential
      confounders. METHODS: 2006 Behavioral Risk Factor Surveillance Survey (BRFSS)
      data were analyzed to identify factors associated with increased odds of partial
      or full edentulism. This year of BRFSS data was chosen for analysis because in
      this year the standardized and validated Personal Health Questionnaire-8 (PHQ-8)
      was used to measure current depression. This measure was part of the optional
      questions BRFSS asks, and in 2006 33 states and/or territories included them in
      their annual surveillance data collection. Bivariate and logistic regression
      analyses were performed on weighted BRFSS data. RESULTS: Logistic regression
      analysis using either full or partial edentulism as the dependent variable
      yielded that rural residency or living in a rural locale, low and/or middle
      socioeconomic status (SES), depression as measured by the PHQ-8, and African
      American race/ethnicity were all independent risk factors when controlling for
      these and a number of additional covariates. CONCLUSIONS: This study adds to the
      epidemiological literature by assessing partial and full edentulism in the US
      utilizing data from the CDC's Behavioral Risk Factor Surveillance System (BRFSS).
      Examining data collected through a large national surveillance system such as
      BRFSS allows for an analysis that incorporates an array of covariates not
      available from clinically-based data alone. This study demonstrated that current
      depression and rural residency are important factors related to partial and full
      edentulism after controlling for potential confounders.

PMID- 24450755
TI  - Association between photosynthesis and contrasting features of minor veins in
      leaves of summer annuals loading phloem via symplastic versus apoplastic routes.
AB  - Foliar vascular anatomy and photosynthesis were evaluated for a number of summer
      annual species that either load sugars into the phloem via a symplastic route
      (Cucumis sativus L. cv. Straight Eight; Cucurbita pepo L. cv. Italian Zucchini
      Romanesco; Citrullus lanatus L. cv. Faerie Hybrid; Cucurbita pepo L. cv. Autumn
      Gold) or an apoplastic route (Nicotiana tabacum L.; Solanum lycopersicum L. cv.
      Brandywine; Gossypium hirsutum L.; Helianthus annuus L. cv. Soraya), as well as
      winter annual apoplastic loaders (Spinacia oleracea L. cv. Giant Nobel;
      Arabidopsis thaliana (L.) Heynhold Col-0, Swedish and Italian ecotypes). For all
      summer annuals, minor vein cross-sectional xylem area and tracheid number as well
      as the ratio of phloem loading cells to phloem sieve elements, each when
      normalized for foliar vein density (VD), was correlated with photosynthesis.
      These links presumably reflect (1) the xylem's role in providing water to meet
      foliar transpirational demand supporting photosynthesis and (2) the importance of
      the driving force of phloem loading as well as the cross-sectional area for
      phloem sap flux to match foliar photosynthate production. While photosynthesis
      correlated with the product of VD and cross-sectional phloem cell area among
      symplastic loaders, photosynthesis correlated with the product of VD and phloem
      cell number per vein among summer annual apoplastic loaders. Phloem cell size has
      thus apparently been a target of selection among symplastic loaders (where
      loading depends on enzyme concentration within loading cells) versus phloem cell
      number among apoplastic loaders (where loading depends on membrane transporter
      numbers). 

PMID- 24450756
TI  - Strategic and non-strategic problem gamblers differ on decision-making under risk
      and ambiguity.
AB  - AIMS: To analyse problem gamblers' decision-making under conditions of risk and
      ambiguity, investigate underlying psychological factors associated with their
      choice behaviour and examine whether decision-making differed in strategic (e.g.,
      sports betting) and non-strategic (e.g., electronic gaming machine) problem
      gamblers. DESIGN: Cross-sectional study. SETTING: Out-patient treatment centres
      and university testing facilities in Victoria, Australia. PARTICIPANTS: Thirty
      nine problem gamblers and 41 age, gender and estimated IQ-matched controls.
      MEASUREMENTS: Decision-making tasks included the Iowa Gambling Task (IGT) and a
      loss aversion task. The Prospect Valence Learning (PVL) model was used to provide
      an explanation of cognitive, motivational and response style factors involved in
      IGT performance. FINDINGS: Overall, problem gamblers performed more poorly than
      controls on both the IGT (P = 0.04) and the loss aversion task (P = 0.01), and
      their IGT decisions were associated with heightened attention to gains (P =
      0.003) and less consistency (P = 0.002). Strategic problem gamblers did not
      differ from matched controls on either decision-making task, but non-strategic
      problem gamblers performed worse on both the IGT (P = 0.006) and the loss
      aversion task (P = 0.02). Furthermore, we found differences in the PVL model
      parameters underlying strategic and non-strategic problem gamblers' choices on
      the IGT. CONCLUSIONS: Problem gamblers demonstrated poor decision-making under
      conditions of risk and ambiguity. Strategic (e.g. sports betting, poker) and non
      strategic (e.g. electronic gaming machines) problem gamblers differed in decision
      making and the underlying psychological processes associated with their
      decisions.

PMID- 24450757
TI  - Evaluation of the cytocompatibility hemocompatibility in vivo bone tissue
      regenerating capability of different PCL blends.
AB  - In this study, the optimized formulations of polycaprolactone (PCL) combined with
      poly(lactic-co-glycolic acid) (PLGA), gelatin (GEL), and biphasic calcium
      phosphate (BCP) were analyzed in terms of cytocompatibility with bone-related
      cells, hemocompatibility, and in vivo bone-regenerating capacity to determine
      their potentials for bone tissue regeneration. Fiber morphology of PCL/GEL and
      PCL/BCP electrospun mats considerably differs from that of the PCL membrane.
      Based on the contact angle analyses, the addition of GEL and PLGA was shown to
      reduce the hydrophobicity of these membranes. The assessment of in vitro
      cytocompatibility using MC3T3-E1 cells indicated that all of the membranes were
      suitable for pre-osteoblast proliferation and adhesion, with PCL/BCP having a
      significantly higher reading after seven days of incubation. The results of the
      in vitro hemocompatibility of the different fibrous scaffolds suggest that
      coagulation and platelet adhesion were higher for hydrophobic membranes (PCL and
      PCL/PLGA), while hemolysis can be associated with fiber morphology. The potential
      of the membranes for bone regeneration was determined by analyzing the microCT
      data and tissue sections of samples implanted in 5 mm sized defects (one and two
      months). Although all of the membranes were suitable for pre-osteoblast
      proliferation, in vivo bone regeneration after two months was found to be
      significantly higher in PCL/BCP (p < 0.001). 

PMID- 24450758
TI  - Evolution of vegetation and soil nutrients after uranium mining in Los Ratones
      mine (Caceres, Spain).
AB  - The evolution of vegetation structure following mine rehabilitation is rather
      scarce in the literature. The concentration of long-lived radionuclides of the
      (238)U series might have harmful effects on living organisms. We studied soil
      properties and the natural vegetation occurring along a gradient in Los Ratones,
      an area rehabilitated after uranium mining located in Caceres, Spain. Soil and
      vegetation were sampled seasonally and physical and chemical properties of soil
      were analysed, including natural isotopes of (238)U, (230)Th, (226)Ra and
      (210)Pb. Species richness, diversity, evenness and plant cover were estimated and
      correlated in relation to soil physical and chemical variables. The location of
      the sampling sites along a gradient had a strong explanatory effect on the
      herbaceous species, as well as the presence of shrubs and trees. Seasonal effects
      of the four natural isotopes were observed in species richness, species diversity
      and plant cover; these effects were directly related to the pH values in the
      soil, this being the soil property that most influences the plant distribution.
      Vegetation in the studied area resembles that of the surroundings, thus proving
      that the rehabilitation carried out in Los Ratones mine was successful in terms
      of understorey cover recovery. 

PMID- 24450759
TI  - Identification of early diagnostic antigens from major excretory-secretory
      proteins of Trichinella spiralis muscle larvae using immunoproteomics.
AB  - BACKGROUND: The excretory-secretory (ES) proteins of Trichinella spiralis muscle
      larvae (ML) come mainly from the excretory granules of the stichosome and the
      cuticles (membrane proteins), are directly exposed to the host's immune system,
      and are the main target antigens, which induce the immune responses. Although the
      ES proteins are the most commonly used diagnostic antigens for trichinellosis,
      their main disadvantage are the false negative results during the early stage of
      infection. The aim of this study was to identify early specific diagnostic
      antigens from the main components of T. spiralis muscle larval ES proteins.
      METHODS: Two-dimensional electrophoresis (2-DE) combined with Western blot were
      used to screen the early diagnostic antigens from the main components of T.
      spiralis muscle larval ES proteins. The protein spots recognized by the sera from
      BALB/c mice infected with T. spiralis at 18 days post-infection (dpi) were
      identified by MALDI-TOF/TOF-MS and putatively annotated using GO terms obtained
      from the InterPro databases. RESULTS: The ES proteins were analyzed by 2-DE, and
      more than 33 protein spots were detected with molecular weight varying from 40 to
      60 kDa and isoelectric point (pI) from 4 to 7. When probed with the sera from
      infected mice at 18 dpi, 21 protein spots were recognized and then identified,
      and they were characterized to correlate with five different proteins of T.
      spiralis, including two serine proteases, one deoxyribonuclease (DNase) II, and
      two kinds of trypsin. The five proteins were functionally categorized into
      molecular function and biological process according to GO hierarchy. CONCLUSIONS:
      2-DE and Western blot combined with MALDI-TOF/TOF-MS were used to screen the
      diagnostic antigens from the main components of T. spiralis muscle larval ES
      proteins. The five proteins of T. spiralis identified (two serine proteases,
      DNase II and two kinds of trypsin) might be the early specific diagnostic
      antigens of trichinellosis.

PMID- 24450760
TI  - Faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae
      is common 12 months after infection and is related to strain factors.
AB  - We aimed to determine the duration of faecal carriage of extended-spectrum beta
      lactamase (ESBL) -producing Enterobacteriaceae (EPE) in patients with clinical
      infection caused by an EPE, to study host strains during carriage, and to
      identify factors associated with prolonged carriage. Patients (n = 61) were
      followed with faecal samples and questionnaires about antimicrobial treatment and
      risk factors for EPE, 1, 3, 6 and 12 months after EPE infection. The EPE isolates
      were subjected to ESBL genotyping, epidemiological typing with pulsed-field gel
      electrophoresis and PCR-based replicon typing. Escherichia coli isolates were
      analysed with PCR for phylogrouping, detection of pabB (ST131) and virulence
      content. Patient-related and strain-related variables were compared for carriers
      and non-carriers at 12 months. Carriage of EPE was observed in 51 of 61 (84%)
      patients after 1 month, 36 of 61 (66%) after 3 months, 31 of 61 (55%) after 6
      months and 26 of 61 (43%) after 12 months. Of the 26 carriers at 12 months, five
      had previous negative samples. In 17 of 61 patients, ESBL was found in a new
      bacterial species and/or strain during carriage. Among E. coli, 14 of 49 belonged
      to the international clone ST131. Phylogroup B2 and CTX-M-gr.-9 were associated
      with being carriers at 12 months (OR 4.3, 95% CI 1.1-16.3 and OR 6.4, 95% CI 1.3
      30.9, respectively). In conclusion, EPE carriage is common 12 months after
      infection and persisting carriage may be associated with E. coli phylogroup B2
      and CTX-M-gr.-9. The host strain frequently changes throughout carriage and
      negative samples do not imply eliminated carriage. 

PMID- 24450762
TI  - The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as
      transcription factor-specific mitochondrial and other cell activities.
AB  - BACKGROUND: Our interest in Candida albicans mitochondria began with the
      identification of GOA1. We demonstrated its role in cell energy production, cross
      talk among mitochondria and peroxisomes, non-glucose energy metabolism,
      maintenance of stationary phase growth, and prevention of premature apoptosis.
      Its absence results in avirulence. However, what regulated transcription of GOA1
      was unknown. RESULTS: To identify transcriptional regulators (TRs) of GOA1, we
      screened a C. albicans TF knockout library (TRKO) and identified Rbf1p, Hfl1p,
      and Dpb4p as positive TRs of GOA1. The phenotypes of each mutant (reduced
      respiration, inability to grow on glycerol, reduced ETC CI and CIV activities)
      are reasonable evidence for their required roles especially in mitochondrial
      functions. While the integration of mitochondria with cell metabolic activities
      is presumed to occur, there is minimal information on this subject at the genome
      level. Therefore, microarray analysis was used to provide this information for
      each TR mutant. Transcriptional profiles of Rbf1p and Hfl1p are more similar than
      that of Dpn4p. Our data demonstrate common and also gene-specific regulatory
      functions for each TR. We establish their roles in carbon metabolism, stress
      adaptation, cell wall synthesis, transporter efflux, peroxisomal metabolism,
      phospholipid synthesis, rRNA processing, and nuclear/mtDNA replication.
      CONCLUSIONS: The TRs regulate a number of common genes but each also regulates
      specific gene transcription. These data for the first time create a genome
      roadmap that can be used to integrate mitochondria with other cell processes. Of
      interest, the TRs are fungal-specific, warranting consideration as antifungal
      drug targets.

PMID- 24450764
TI  - In vitro bioaccessibility of phenolics and vitamins from durum wheat aleurone
      fractions.
AB  - Durum wheat aleurone, thanks to its nutrient-rich composition, might be of
      potential use as a functional ingredient in cereal-based foods provided nutrients
      can be made available for absorption. We evaluated the in vitro bioaccessibility
      of thiamine, niacin, and phenolic acids in different aleurone fractions obtained
      with an industrial processing aimed to obtain material of different composition
      and particle size. Results indicate that the main phenolic compounds and vitamins
      investigated have a higher bioaccessibility when present in the inner part of the
      aleurone layer compared to the outer part of aleurone or the unfractionated bran.
      Moreover, an ultramicronization treatment employed to reduce particle size does
      not further improve the bioaccessibility of these compounds. We conclude that
      aleurone fractions from durum wheat bran could represent a nutritionally relevant
      ingredient, bringing together a high fiber content and an excellent
      bioaccessibility of vitamins and phytochemicals generally associated with
      nutritional benefits. 

PMID- 24450763
TI  - Choosing healthier foods in recreational sports settings: a mixed methods
      investigation of the impact of nudging and an economic incentive.
AB  - BACKGROUND: Nudging is an approach to environmental change that alters social and
      physical environments to shift behaviors in positive, self-interested directions.
      Evidence indicates that eating is largely an automatic behavior governed by
      environmental cues, suggesting that it might be possible to nudge healthier
      dietary behaviors. This study assessed the comparative and additive efficacy of
      two nudges and an economic incentive in supporting healthy food purchases by
      patrons at a recreational swimming pool. METHODS: An initial pre-intervention
      period was followed by three successive and additive interventions that promoted
      sales of healthy items through: signage, taste testing, and 30% price reductions;
      concluding with a return to baseline conditions. Each period was 8 days in
      length. The primary outcome was the change in the proportion of healthy items
      sold in the intervention periods relative to pre- and post-intervention in the
      full sample, and in a subsample of patrons whose purchases were directly
      observed. Secondary outcomes included change in the caloric value of purchases,
      change in revenues and gross profits, and qualitative process observations. Data
      were analyzed using analysis of covariance, chi-square tests and thematic content
      analysis. RESULTS: Healthy items represented 41% of sales and were significantly
      lower than sales of unhealthy items (p < 0.0001). In the full sample, sales of
      healthy items did not differ across periods, whereas in the subsample, sales of
      healthy items increased by 30% when a signage + taste testing intervention was
      implemented (p < 0.01). This increase was maintained when prices of healthy items
      were reduced by 30%, and when all interventions were removed. When adults were
      alone they purchased more healthy items compared to when children were present
      during food purchases (p < 0.001), however parental choices were not
      substantially better than choices made by children alone. CONCLUSIONS: This study
      found mixed evidence for the efficacy of nudging in cueing healthier dietary
      behaviors. Moreover, price reductions appeared ineffectual in this setting. Our
      findings point to complex, context-specific patterns of effectiveness and suggest
      that nudging should not supplant the use of other strategies that have proven to
      promote healthier dietary behaviors.

PMID- 24450765
TI  - Strictly conserved lysine of prolyl-tRNA Synthetase editing domain facilitates
      binding and positioning of misacylated tRNA(Pro.).
AB  - To ensure high fidelity in translation, many aminoacyl-tRNA synthetases, enzymes
      responsible for attaching specific amino acids to cognate tRNAs, require proof
      reading mechanisms. Most bacterial prolyl-tRNA synthetases (ProRSs) misactivate
      alanine and employ a post-transfer editing mechanism to hydrolyze Ala-tRNA(Pro).
      This reaction occurs in a second catalytic site (INS) that is distinct from the
      synthetic active site. The 2'-OH of misacylated tRNA(Pro) and several conserved
      residues in the Escherichia coli ProRS INS domain are directly involved in Ala
      tRNA(Pro) deacylation. Although mutation of the strictly conserved lysine 279
      (K279) results in nearly complete loss of post-transfer editing activity, this
      residue does not directly participate in Ala-tRNA(Pro) hydrolysis. We
      hypothesized that the role of K279 is to bind the phosphate backbone of the
      acceptor stem of misacylated tRNA(Pro) and position it in the editing active
      site. To test this hypothesis, we carried out pKa, charge neutralization, and
      free-energy of binding calculations. Site-directed mutagenesis and kinetic
      studies were performed to verify the computational results. The calculations
      revealed a considerably higher pKa of K279 compared to an isolated lysine and
      showed that the protonated state of K279 is stabilized by the neighboring acidic
      residue. However, substitution of this acidic residue with a positively charged
      residue leads to a significant increase in Ala-tRNA(Pro) hydrolysis, suggesting
      that enhancement in positive charge density in the vicinity of K279 favors tRNA
      binding. A charge-swapping experiment and free energy of binding calculations
      support the conclusion that the positive charge at position 279 is absolutely
      necessary for tRNA binding in the editing active site. 

PMID- 24450766
TI  - Trends in the prevalence of gestational diabetes mellitus in southern Sweden,
      2003-2012.
AB  - There is accumulating evidence that gestational diabetes is a growing problem.
      The lack of internationally standardized diagnostic procedures prevents
      consistent diagnosis and the burden of gestational diabetes must be determined in
      country-specific studies. In southern Sweden, gestational diabetes is defined as
      a 2-h capillary plasma glucose concentration of >=10.0 mmol/L during a universal
      75-g oral glucose tolerance test. We report the crude prevalence of gestational
      diabetes during the years 2003-2012. Of 156 144 women who gave birth, 2.2% were
      diagnosed with gestational diabetes. When the effect of time on the prevalence of
      gestational diabetes was assessed in a log-linear Poisson model, an overall
      increase in prevalence of 35% was predicted, corresponding to an average annual
      increase of 3.4%. Predicted prevalence was 1.9 (95% CI 1.8-2.0) in 2003 and 2.6
      (95% CI 2.4-2.7) in 2012 (p < 0.0001). Due to a simultaneous rise in birth rate,
      the number of women diagnosed with gestational diabetes increased by 64%. 

PMID- 24450767
TI  - Sarcoidosis associated with cosmetic fillers.

PMID- 24450768
TI  - Assessment of the hepatic CYP reductase null mouse model and its potential
      application in drug discovery.
AB  - CYP Oxidoreductase (Por) is the essential electron donor for all CYP enzymes and
      is responsible for the activation of CYP. The Taconic Hepatic CYP Reductase Null
      (HRN) mouse model possesses a targeted mutation that results in liver-specific
      deletion of the Por gene thereby resulting in a disruption of CYP metabolism in
      the liver. The objectives of these studies were to further characterize the HRN
      mouse using probe drugs metabolized by CYP. In addition, tumor exposure in
      xenograft tumor bearing HRN immune-compromised (nude) mice was also determined.
      In HRN mice following intravenous (iv) administration of midazolam, clearance
      (CL) was reduced by ~ 80% compared to wild-type mice (WT). After oral
      administration, the AUC of midazolam was increased by ~ 20-fold in HRN mice
      compared to WT mice; this greater effect suggests that hepatic first pass plays a
      role in the oral CL of midazolam. A 50% and an 80% decrease in CL were also
      observed in HRN mice following iv administration of docetaxel and theophylline,
      respectively, compared to WT mice. In addition, a 2- to 3-fold increase in tumor
      concentrations of G4222, a tool compound, were observed in tumor bearing HRN nude
      mice compared to tumor bearing nude WT mice. The observations from these
      experiments demonstrate that, for compounds that are extensively metabolized by
      hepatic CYP, the HRN mouse model could potentially be valuable for evaluating in
      vivo efficacy of tool compounds in drug discovery where high hepatic CL and low
      exposure may prevent in vivo evaluation of a new chemical entity.

PMID- 24450769
TI  - Light-dependent reversible phosphorylation of the minor photosystem II antenna
      Lhcb6 (CP24) occurs in lycophytes.
AB  - Evolution of vascular plants required compromise between photosynthesis and
      photodamage. We analyzed representative species from two divergent lineages of
      vascular plants, lycophytes and euphyllophytes, with respect to the response of
      their photosynthesis and light-harvesting properties to increasing light
      intensity. In the two analyzed lycophytes, Selaginella martensii and Lycopodium
      squarrosum, the medium phase of non-photochemical quenching relaxation increased
      under high light compared to euphyllophytes. This was thought to be associated
      with the occurrence of a further thylakoid phosphoprotein in both lycophytes, in
      addition to D2, CP43 and Lhcb1-2. This protein, which showed light intensity
      dependent reversible phosphorylation, was identified in S. martensii as Lhcb6, a
      minor LHCII antenna subunit of PSII. Lhcb6 is known to have evolved in the
      context of land colonization. In S. martensii, Lhcb6 was detected as a component
      of the free LHCII assemblies, but also associated with PSI. Most of the light
      induced changes affected the amount and phosphorylation of the LHCII assemblies,
      which possibly mediate PSI-PSII connectivity. We propose that Lhcb6 is involved
      in light energy management in lycophytes, participating in energy balance between
      PSI and PSII through a unique reversible phosphorylation, not yet observed in
      other land plants. 

PMID- 24450770
TI  - Protic ionic liquids and salts as versatile carbon precursors.
AB  - Instead of traditional polymer precursors and complex procedures, easily prepared
      and widely obtainable nitrogen-containing protic ionic liquids and salts were
      explored as novel, small-molecule precursors to prepare carbon materials (CMs)
      via direct carbonization without other treatments. Depending on the precursor
      structure, the resultant CMs can be readily obtained with a relative yield of up
      to 95.3%, a high specific surface area of up to 1380 m(2)/g, or a high N content
      of up to 11.1 wt%, as well as a high degree of graphitization and high
      conductivity (even higher than that of graphite). One of the carbons, which
      possesses a high surface area and a high content of pyridinic N, exhibits
      excellent electrocatalytic activity toward the oxygen reduction reaction in an
      alkaline medium, as revealed by an onset potential, half-wave potential, and
      kinetic current density comparable to those of commercial 20 wt% Pt/C. These low
      cost and versatile precursors are expected to be important building blocks for
      CMs. 

PMID- 24450771
TI  - Co-occurrence of anaerobic bacteria in colorectal carcinomas.
AB  - BACKGROUND: Numerous cancers have been linked to microorganisms. Given that
      colorectal cancer is a leading cause of cancer deaths and the colon is
      continuously exposed to a high diversity of microbes, the relationship between
      gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic
      studies have shown an association between Fusobacterium species and colorectal
      carcinoma. Here, we have extended these studies with deeper sequencing of a much
      larger number (n = 130) of colorectal carcinoma and matched normal control
      tissues. We analyzed these data using co-occurrence networks in order to identify
      microbe-microbe and host-microbe associations specific to tumors. RESULTS: We
      confirmed tumor over-representation of Fusobacterium species and observed
      significant co-occurrence within individual tumors of Fusobacterium, Leptotrichia
      and Campylobacter species. This polymicrobial signature was associated with over
      expression of numerous host genes, including the gene encoding the pro
      inflammatory chemokine Interleukin-8. The tumor-associated bacteria we have
      identified are all Gram-negative anaerobes, recognized previously as constituents
      of the oral microbiome, which are capable of causing infection. We isolated a
      novel strain of Campylobacter showae from a colorectal tumor specimen. This
      strain is substantially diverged from a previously sequenced oral Campylobacter
      showae isolate, carries potential virulence genes, and aggregates with a
      previously isolated tumor strain of Fusobacterium nucleatum. CONCLUSIONS: A
      polymicrobial signature of Gram-negative anaerobic bacteria is associated with
      colorectal carcinoma tissue.

PMID- 24450772
TI  - The cAMP-PKA pathway regulates growth, sexual and asexual differentiation, and
      pathogenesis in Fusarium graminearum.
AB  - Like many other filamentous ascomycetes, Fusarium graminearum contains two genes
      named CPK1 and CPK2 that encode the catalytic subunits of cyclic AMP (cAMP)
      dependent protein kinase A (PKA). To determine the role of cAMP signaling in
      pathogenesis and development in F. graminearum, we functionally characterized
      these two genes. In addition, we generated and characterized the cpk1 cpk2 double
      and fac1 adenylate cyclase gene deletion mutants. The cpk1 mutant was
      significantly reduced in vegetative growth, conidiation, and deoxynivalenol
      production but it had increased tolerance to elevated temperatures. It was
      defective in the production of penetration branches on plant surfaces,
      colonization of wheat rachises, and spreading in flowering wheat heads. Deletion
      of CPK1 had no effect on perithecium development but the cpk1 mutant was
      defective in ascospore maturation and releasing. In contrast, the cpk2 mutant had
      no detectable phenotypes, suggesting that CPK2 contributes minimally to PKA
      activities in F. graminearum. Nevertheless, the cpk1 cpk2 double mutant had more
      severe defects in vegetative growth and rarely produced morphologically abnormal
      conidia. The double mutant, unlike the cpk1 or cpk2 mutant, was nonpathogenic and
      failed to form perithecia on self-mating plates. Therefore, CPK1 and CPK2 must
      have overlapping functions in vegetative growth, differentiation, and plant
      infection in F. graminearum. The fac1 mutant was also nonpathogenic and had
      growth defects similar to those of the cpk1 cpk2 mutant. However, deletion of
      FAC1 had no effect on conidium morphology. These results indicated that CPK1 is
      the major PKA catalytic subunit gene and that the cAMP-PKA pathway plays critical
      roles in hyphal growth, conidiation, ascosporogenesis, and plant infection in F.
      graminearum. 

PMID- 24450773
TI  - OxyR and SoxR modulate the inducible oxidative stress response and are implicated
      during different stages of infection for the bacterial phytopathogen Pantoea
      stewartii subsp. stewartii.
AB  - Reactive oxygen species (ROS) from a variety of sources are often encountered by
      invading plant pathogens during the infection process. Pantoea stewartii subsp.
      stewartii, the etiological agent of Stewart's wilt, is a serious bacterial
      pathogen of sweet corn that colonizes both the apoplast and xylem tissues in
      which ROS are produced. The P. stewartii genome predicts the presence of two
      redox-sensing transcriptional regulators, OxyR and SoxR, which both activate gene
      expression in response to oxidative stress. ROS exposure in the form of hydrogen
      peroxide and the superoxide-generating compound paraquat initiates an induced
      stress response through OxyR and SoxR that includes activation of the ROS
      detoxifying enzymes alkyl hydroperoxide reductase and superoxide dismutase. P.
      stewartii DeltasoxR was more sensitive to paraquat and was compromised in the
      ability to form water-soaked lesions, while DeltaoxyR was more sensitive to
      hydrogen peroxide treatment and was deficient in exopolysaccharide production and
      the elicitation of wilting symptoms. This demonstrates that both SoxR and OxyR
      play an important role in virulence in the different niches that P. stewartii
      colonize during the infection process. 

PMID- 24450774
TI  - Salicylic acid and jasmonic acid are essential for systemic resistance against
      tobacco mosaic virus in Nicotiana benthamiana.
AB  - Systemic resistance is induced by pathogens and confers protection against a
      broad range of pathogens. Recent studies have indicated that salicylic acid (SA)
      derivative methyl salicylate (MeSA) serves as a long-distance phloem-mobile
      systemic resistance signal in tobacco, Arabidopsis, and potato. However, other
      experiments indicate that jasmonic acid (JA) is a critical mobile signal. Here,
      we present evidence suggesting both MeSA and methyl jasmonate (MeJA) are
      essential for systemic resistance against Tobacco mosaic virus (TMV), possibly
      acting as the initiating signals for systemic resistance. Foliar application of
      JA followed by SA triggered the strongest systemic resistance against TMV.
      Furthermore, we use a virus-induced gene-silencing-based genetics approach to
      investigate the function of JA and SA biosynthesis or signaling genes in systemic
      response against TMV infection. Silencing of SA or JA biosynthetic and signaling
      genes in Nicotiana benthamiana plants increased susceptibility to TMV. Genetic
      experiments also proved the irreplaceable roles of MeSA and MeJA in systemic
      resistance response. Systemic resistance was compromised when SA methyl
      transferase or JA carboxyl methyltransferase, which are required for MeSA and
      MeJA formation, respectively, were silenced. Moreover, high-performance liquid
      chromatography-mass spectrometry analysis indicated that JA and MeJA accumulated
      in phloem exudates of leaves at early stages and SA and MeSA accumulated at later
      stages, after TMV infection. Our data also indicated that JA and MeJA could
      regulate MeSA and SA production. Taken together, our results demonstrate that
      (Me)JA and (Me)SA are required for systemic resistance response against TMV. 

PMID- 24450775
TI  - Amino acid sequence motifs essential for P0-mediated suppression of RNA silencing
      in an isolate of potato leafroll virus from Inner Mongolia.
AB  - Polerovirus P0 suppressors of host gene silencing contain a consensus F-box-like
      motif with Leu/Pro (L/P) requirements for suppressor activity. The Inner
      Mongolian Potato leafroll virus (PLRV) P0 protein (P0(PL-IM)) has an unusual F
      box-like motif that contains a Trp/Gly (W/G) sequence and an additional GW/WG
      like motif (G139/W140/G141) that is lacking in other P0 proteins. We used
      Agrobacterium infiltration-mediated RNA silencing assays to establish that P0(PL
      IM) has a strong suppressor activity. Mutagenesis experiments demonstrated that
      the P0(PL-IM) F-box-like motif encompasses amino acids 76-LPRHLHYECLEWGLLCG THP
      95, and that the suppressor activity is abolished by L76A, W87A, or G88A
      substitution. The suppressor activity is also weakened substantially by mutations
      within the G139/W140/G141 region and is eliminated by a mutation (F220R) in a C
      terminal conserved sequence of P0(PL-IM). As has been observed with other P0
      proteins, P0(PL-IM) suppression is correlated with reduced accumulation of the
      host AGO1-silencing complex protein. However, P0(PL-IM) fails to bind SKP1, which
      functions in a proteasome pathway that may be involved in AGO1 degradation. These
      results suggest that P0(PL-IM) may suppress RNA silencing by using an alternative
      pathway to target AGO1 for degradation. Our results help improve our
      understanding of the molecular mechanisms involved in PLRV infection. 

PMID- 24450776
TI  - The effects of lowering nighttime and breakfast glucose levels with sensor
      augmented pump therapy on hemoglobin A1c levels in type 1 diabetes.
AB  - OBJECTIVE: This study determined the association of continuous glucose monitoring
      glucose (CGM-glucose) levels at different times of the day with improvement in
      glycated hemoglobin (HbA1c) levels. The potential application of these data is to
      focus effort to improve glucose control in patients with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: Data were analyzed from 196 patients with type 1
      diabetes who were randomized to receive sensor-augmented pump therapy in the 1
      year STAR 3 trial. CGM-glucose values and HbA1c levels from baseline and after 1
      year were evaluated to determine associations of improvement in CGM-glucose at
      different times of the day with longitudinal improvement in HbA1c. RESULTS:
      Improvement in HbA1c levels after 1 year was related to improvement in mean CGM
      glucose levels in daytime (6 a.m.-midnight), overnight (midnight-6 a.m.), and
      each mealtime period (P<0.0001 for each). In multivariable analysis, only
      improvement in breakfast meal period was associated with improvement in HbA1c
      after 1 year, explaining 59% of the HbA1c improvement using the partial R(2)
      test. Moreover, among those patients who only improved CGM-glucose in the
      overnight period there was an associated improvement in breakfast meal period CGM
      glucose of 26 +/- 22 mg/dL (P<0.01). CONCLUSIONS: Breakfast period glucose
      improvement had the greatest effect on lowering HbA1c levels in patients with
      type 1 diabetes. Improving glucose control overnight resulted in subsequent
      improvement in the breakfast period. Although glucose control should be improved
      at all times, methods to improve overnight and post-breakfast glucose levels may
      be of primary importance in improving glucose control in patients with type 1
      diabetes.

PMID- 24450777
TI  - FEV(1)/FEV(6) to diagnose airflow obstruction. Comparisons with computed
      tomography and morbidity indices.
AB  - RATIONALE: FVC is a difficult maneuver for many patients, and forced expiratory
      volume in 6 seconds (FEV6) has been proposed as a surrogate for FVC for the
      diagnosis of chronic obstructive pulmonary disease (COPD). Previous studies have
      performed head-to-head comparisons of these thresholds but did not examine their
      relationships with structural lung disease, symptoms, or exacerbations.
      OBJECTIVES: To compare FEV1/FEV6 with FEV1/FVC in the diagnosis of COPD-related
      morbidity and structural lung disease as assessed by CT. METHODS: We analyzed
      data from a large multicenter cohort study (COPDGene) that included current and
      former smokers (age 45-80 yr). Accuracy and concordance between the two ratios in
      diagnosing structural COPD was compared using CT measures of emphysema and airway
      disease and COPD-related morbidity to assess how the two ratios compare in
      defining disease. RESULTS: A total of 10,018 subjects were included. FEV1/FEV6
      showed excellent accuracy in diagnosing airflow obstruction using FEV1/FVC < 0.70
      as a reference (area under curve, 0.99; 95% confidence interval [CI], 0.989
      0.992; P < 0.001). FEV1/FEV6 < 0.73 had the best sum of sensitivity (92.1%; 95%
      CI, 90.8-92.4) and specificity (97.3%; 95% CI, 97.3-98.1). There was excellent
      agreement between the two diagnostic cutoffs (kappa = 0.90; 95% CI, 0.80-0.91; P
      < 0.001). In comparison with control subjects and those positive by FEV1/FVC
      alone, subjects positive by FEV1/FEV6 alone had greater gas trapping and airway
      wall thickness, worse functional capacity, and a greater number of exacerbations
      on follow-up. These relationships held true when disease definitions were made
      using the lower limits of normal. CONCLUSIONS: FEV1/FEV6 can be substituted for
      FEV1/FVC in diagnosing airflow obstruction and may better predict COPD-related
      pathology and morbidity.

PMID- 24450778
TI  - A multinational study of colonization with extended spectrum beta-lactamase
      producing Enterobacteriaceae in healthcare personnel and family members of
      carrier patients hospitalized in rehabilitation centres.
AB  - The study aims were: (i) to define the prevalence of and risk factors for
      colonization by extended spectrum beta-lactamase (ESBL) -producing
      Enterobacteriaceae (EPE) among healthcare workers (HCWs) and family members (FMs)
      of EPE-colonized patients in rehabilitation units and (ii) to compare EPE
      isolates from these three groups. The study included 286 FMs of 194 EPE-carrying
      patients identified in five rehabilitation units located in Israel, Italy, France
      and Spain. The EPE were detected in rectal swabs from 26 (9%) of 286 FMs
      screened. In multivariate analyses, older age of FM, greater mean number of hours
      spent with the patient, being a daughter or a female spouse of a patient, and
      chronic lung disease of the patient were significantly associated with carriage
      in the FM. Escherichia coli was the most common organism (76%), followed by
      Klebsiella pneumoniae (19%). Isolates were typed by pulsed field gel
      electrophoresis and multilocus sequence typing, and ESBLs were identified by PCR
      sequencing. A comparison of paired species isolates from FMs and their respective
      patient showed that 17 of 23 strains were indistinguishable. EPE were detected in
      35 (3.5%, E. coli = 34) of the 1001 HCWs screened. Feeding patients was
      associated with EPE carriage by HCWs. Only 7 of 23 E. coli subclones cultured
      from HCWs were also represented among 376 patient-derived ESBL-producing E. coli
      isolates from the same rehabilitation units. In Spain, a higher proportion of
      HCWs and FMs were ESBL carriers than elsewhere (p <0.05). In conclusion, the
      molecular and epidemiological data suggest that FMs are at higher risk of EPE
      acquisition from their relative patients than HCWs. 

PMID- 24450781
TI  - Reduction of low temperature engine pollutants by understanding the exhaust
      species interactions in a diesel oxidation catalyst.
AB  - The interactions between exhaust gas species and their effect (promotion or
      inhibition) on the light-off and activity of a diesel oxidation catalyst (DOC)
      for the removal of pollutants are studied, using actual engine exhaust gases from
      the combustion of diesel, alternative fuels (rapeseed methyl ester and gas-to
      liquid fuel) and diesel/propane dual fuel combustion. The activity of the
      catalyst was recorded during a heating temperature ramp where carbon monoxide
      (CO) and hydrocarbon (HC) light-off curves were obtained. From the catalyst
      activity tests, it was found that the presence of species including CO, medium
      heavy HC, alkenes, alkanes, and NOx and their concentration influence the
      catalyst ability to reduce CO and total HC emissions before release to the
      atmosphere. CO could inhibit itself and other species oxidation (e.g., light and
      medium-heavy hydrocarbons) while suffering from competitive adsorption with NO.
      Hydrocarbon species were also found to inhibit their own oxidation as well as CO
      through adsorption competition. On the other hand, NO2 was found to promote low
      temperature HC oxidation through its partial reduction, forming NO. The
      understanding of these exhaust species interactions within the DOC could aid the
      design of an efficient aftertreatment system for the removal of diesel exhaust
      pollutants. 

PMID- 24450782
TI  - Drinking in social groups. Does 'groupdrink' provide safety in numbers when
      deciding about risk?
AB  - AIMS: To investigate the impact of alcohol consumption on risk decisions taken
      both individually and while part of a four- to six-person ad-hoc group. DESIGN: A
      2 (alcohol: consuming versus not consuming alcohol) * 2 (decision: individual,
      group) mixed-model design; decision was a repeated measure. The dependent
      variable was risk preference, measured using choice dilemmas. SETTING:
      Opportunity sampling in campus bars and a music event at a campus-based
      university in the United Kingdom. PARTICIPANTS: A total of 101 individuals were
      recruited from groups of four to six people who either were or were not consuming
      alcohol. MEASUREMENTS: Participants privately opted for a level of risk in
      response to a choice dilemma and then, as a group, responded to a second choice
      dilemma. The choice dilemmas asked participants the level of accident risk at
      which they would recommend someone could drive while intoxicated. FINDINGS: Five
      three-level multi-level models were specified in the software program HLM 7.
      Decisions made in groups were less risky than those made individually (B = -0.73,
      P < 0.001). Individual alcohol consumers opted for higher risk than non-consumers
      (B = 1.27, P = 0.025). A significant alcohol * decision interaction (B = -2.79, P
      = 0.001) showed that individual consumers privately opted for higher risk than
      non-consumers, whereas risk judgements made in groups of either consumers or non
      consumers were lower. Decisions made by groups of consumers were less risky than
      those made by groups of non-consumers (B = 1.23, P < 0.001). CONCLUSIONS:
      Moderate alcohol consumption appears to produce a propensity among individuals
      towards increased risk-taking in deciding to drive while intoxicated, which can
      be mitigated by group monitoring processes within small (four- to six-person)
      groups.

PMID- 24450785
TI  - 'Fax mentis incendium gloriae'.

PMID- 24450783
TI  - Nisin A extends the shelf life of high-fat chilled dairy dessert, a milk-based
      pudding.
AB  - AIMS: The aims of this study were to evaluate the effectiveness of nisin A to
      control the growth of spore-forming bacteria, Bacillus and Paenibacillus, in
      chilled high-fat, milk pudding and to reduce heat treatment to improve aroma and
      flavour. METHODS AND RESULTS: Nisin A was added to milk pudding containing 5.0
      and 7.5% fat to final concentrations of 40, 80, 120 and 240 IU ml(-1). Spores
      from Bacillus thuringiensis, Bacillus cereus and Paenibacillus jamilae were
      inoculated into samples at 10 spores ml(-1) prior to pasteurization at 130
      degrees C for 2 s. Milk pudding without inoculation was pasteurized using less
      heat condition (100, 110 and 120 degrees C for 2 s) to measure the effect of
      adjusting the ingredients to prevent naturally occurring bacteria. The viable
      cells during storage at 15, 20 and 30 degrees C showed nisin A inhibited spiked
      bacteria to varying degrees depending on species, sensitivities to nisin A
      concentration and fat content, and inhibited natural populations at 80 IU g(-1)
      nisin A in 5.0% fat and at 120 IU g(-1) in 7.5% fat milk pudding. An aroma
      compound analysis and organoleptic assessment showed processing at 110 and 120
      degrees C decreased the temperature-dependent unpleasant odours, for example,
      reduced dimethyl sulfide and dimethyl disulfide by 1.2-1.5 times and increased
      rankings in taste tests compared with 130 degrees C treated pudding. CONCLUSIONS:
      Nisin A was found to be effective as a natural preservative to control spoilage
      bacteria in high-fat milk pudding and extend its shelf life, when using reduced
      heat treatments to improve the flavour and aroma without compromising food
      safety. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing
      nisin A is effective in reducing spoilage bacteria in high-fat, chilled dessert,
      milk pudding. Therefore, nisin A can be used to improve milk puddings to satisfy
      both industry and consumer demand for food quality and safety.

PMID- 24450786
TI  - Breast reconstruction in 2013.

PMID- 24450787
TI  - The arms revisited.

PMID- 24450788
TI  - Increasing breast reconstruction rates by offering more women a choice.
AB  - BACKGROUND: Breast reconstruction (BR) following mastectomy for breast cancer is
      safe and has high rates of patient satisfaction, yet only around 12% of
      Australian women undergo BR. This study presents BR rates and outcomes from a
      specialist practice that discusses reconstruction options with all women
      medically suitable for BR. METHODS: Retrospective clinical study of all women
      that had undergone therapeutic mastectomy between 2009 and 2011. Patient, tumour
      and adjuvant therapy factors, and surgical complication rates, were compared
      between BR and no BR (NBR) patients. RESULTS: Of the 331 women who had mastectomy
      for cancer, 136 (41%) had BR, with the vast majority (132, 97%) opting for
      immediate BR (IBR). Factors significantly associated with BR were young age, pure
      ductal carcinoma in-situ (DCIS), menopausal status and private health insurance.
      The main reasons for NBR were patient choice (88/195, 45%) and surgeon's
      perception of high-risk tumours (63/195, 32%). At mean follow-up of 15.6 months,
      five patients had developed local or distant recurrence (2 BR, 3 NBR). IBR did
      not cause significant delays in commencement of adjuvant therapy, and the BR
      group had a lower rate of surgical complications. DISCUSSION: A BR rate of 41%,
      over three times the national average, was achieved when BR was discussed with
      all patients. This significant gain in BR rate was not accompanied by a
      commensurate increase in adverse outcomes, providing evidence that expanding the
      indications for BR to women who were previously not considered eligible is a
      valid option.

PMID- 24450789
TI  - Response to Re: Alexis Carrel: the good, the bad, the ugly.

PMID- 24450790
TI  - Re: Alexis Carrel: the good, the bad, the ugly.

PMID- 24450792
TI  - Access to digital radiology imaging and the impact on specialists in private
      practice.

PMID- 24450791
TI  - The 'keystone concept': time for more science.

PMID- 24450793
TI  - General surgical trainee's iPhone toolkit: review of 'GenSurgCall' App.

PMID- 24450794
TI  - Response to re: history of lower limb reconstruction after trauma.

PMID- 24450795
TI  - Intranodal haemangioma within parotid gland: a new site for a rare lesion.

PMID- 24450796
TI  - Biological evaluation of human degenerated nucleus pulposus cells in
      functionalized self-assembling peptide nanofiber hydrogel scaffold.
AB  - Nucleus pulposus (NP) tissue engineering has been proposed as a novel biological
      treatment for early-stage intervertebral disc degeneration. In this study, a
      novel functional self-assembling peptide PKP was first designed by linking the
      short functional motif of bone morphogenetic protein-7 (BMP7) to the C-terminal
      of RADA16-I, and another new functional self-assembling peptide was obtained by
      mixing RKP with RADA16-I. Then, the biocompatibilities and bioactivities of RKP
      and RAD-RKP for human degenerated nucleus pulposus cells (hNPCs) were studied in
      vitro. Atomic force microscopy and scanning electron microscopy (SEM) confirmed
      that both RKP and RAD-RKP could self-assemble into three-dimensional (3D)
      nanofiber hydrogel scaffolds in a culture medium at 37 degrees C. After the hNPCs
      were cultured in 3D scaffolds, both RKP and RAD-RKP exhibited reliable attachment
      and extremely low cytotoxicities (<14%), which were verified by SEM and
      cytotoxity assays, respectively. Our results also showed that the functional
      based scaffolds could increase the proliferation and migration of hNPCs after 7
      days compared with culture plates and pure RADA16-I. Quantitative real-time
      polymerase chain reaction demonstrated that the expressions of collagen II
      alpha1, Sox-9, and aggrecan were upregulated, while collagen I alpha1 was
      downregulated by functional-based scaffolds after 28 days. Furthermore, we also
      confirmed that RAD-RKP exhibited a higher hNPC proliferation, migration, and
      expression of Sox-9 and aggrecan compared with pure RKP. Therefore, the results
      of this study indicated that the BMP7 short motif-designed functional self
      assembling peptide nanofiber hydrogels could be used as excellent scaffolds in NP
      tissue engineering, and RAD-RKP might have further potential application in human
      mild degenerated NP tissue regeneration.

PMID- 24450799
TI  - Differential gene expression in small and large rainbow trout derived from two
      seasonal spawning groups.
AB  - BACKGROUND: Growth in fishes is regulated via many environmental and
      physiological factors and is shaped by the genetic background of each individual.
      Previous microarray studies of salmonid growth have examined fish experiencing
      either muscle wastage or accelerated growth patterns following refeeding, or the
      influence of growth hormone and transgenesis. This study determines the gene
      expression profiles of genetically unmanipulated large and small fish from a
      domesticated salmonid strain reared on a typical feeding regime. Gene expression
      profiles of white muscle and liver from rainbow trout (Oncorhynchus mykiss) from
      two seasonal spawning groups (September and December lots) within a single strain
      were examined when the fish were 15 months of age to assess the influence of
      season (late fall vs. onset of spring) and body size (large vs. small). RESULTS:
      Although IGFBP1 gene expression was up-regulated in the livers of small fish in
      both seasonal lots, few expression differences were detected in the liver
      overall. Faster growing Dec. fish showed a greater number of differences in white
      muscle expression compared to Sept. fish. Significant differences in the GO
      Generic Level 3 categories 'response to external stimulus', 'establishment of
      localization', and 'response to stress' were detected in white muscle tissue
      between large and small fish. Larger fish showed up-regulation of cytoskeletal
      component genes while many genes related to myofibril components of muscle tissue
      were up-regulated in small fish. Most of the genes up-regulated in large fish
      within the 'response to stress' category are involved in immunity while in small
      fish most of these gene functions are related to apoptosis. CONCLUSIONS: A higher
      proportion of genes in white muscle compared to liver showed similar patterns of
      up- or down-regulation within the same size class across seasons supporting their
      utility as biomarkers for growth in rainbow trout. Differences between large and
      small Sept. fish in the 'response to stress' and 'response to external stimulus'
      categories for white muscle tissue, suggests that smaller fish have a greater
      inability to handle stress compared to the large fish. Sampling season had a
      significant impact on the expression of genes related to the growth process in
      rainbow trout.

PMID- 24450800
TI  - Diversity of mosquitoes and the aquatic insects associated with their oviposition
      sites along the Pacific coast of Mexico.
AB  - BACKGROUND: The abundance, richness and diversity of mosquitoes and aquatic
      insects associated with their oviposition sites were surveyed along eight states
      of the Pacific coast of Mexico. Diversity was estimated using the Shannon index
      (H'), similarity measures and cluster analysis. METHODS: Oviposition sites were
      sampled during 2-3 months per year, over a three year period. Field collected
      larvae and pupae were reared and identified to species following adult emergence.
      Aquatic insects present at oviposition sites were also collected, counted and
      identified to species or genus. RESULTS: In total, 15 genera and 74 species of
      mosquitoes were identified: Anopheles pseudopunctipennis, An. albimanus and Aedes
      aegypti were the most abundant and widely-distributed species, representing 47%
      of total mosquito individuals sampled. New species records for certain states are
      reported. Anopheline diversity was lowest in Sinaloa state (H' = 0.54) and
      highest in Chiapas (H' = 1.61) and Michoacan (H' = 1.56), whereas culicid
      diversity was lowest in Michoacan (H' = 1.93), Colima (H' = 1.95), Sinaloa (H' =
      1.99) and Jalisco (H' = 2.01) and highest in Chiapas (H' = 2.66). In total, 10
      orders, 57 families, 166 genera and 247 species of aquatic insects were
      identified in samples. Aquatic insect diversity was highest in Chiapas, Oaxaca
      and Michoacan (H' = 3.60-3.75). Mosquito larval/pupal abundance was not
      correlated with that of predatory Coleoptera and Hemiptera. CONCLUSION: This
      represents the first update on the diversity and geographic distribution of the
      mosquitoes and aquatic insects of Mexico in over five decades. This information
      has been cataloged in Mexico's National Biodiversity Information System (SNIB
      CONABIO) for public inspection.

PMID- 24450797
TI  - Outcomes of hepatitis C screening programs targeted at risk groups hidden in the
      general population: a systematic review.
AB  - BACKGROUND: Effective screening programs are urgently needed to provide
      undiagnosed hepatitis C virus (HCV)-infected individuals with therapy. This
      systematic review of characteristics and outcomes of screening programs for HCV
      focuses on strategies to identify HCV risk groups hidden in the general
      population. METHODS: We conducted a comprehensive search of MEDLINE and EMBASE
      databases for articles published between 1991-2010, including studies that
      screened the general population using either a newly developed (nonintegrated)
      screening program or one integrated in existing health care facilities. Look-back
      studies, prevalence studies, and programs targeting high-risk groups in care
      (e.g., current drug users) were excluded. RESULTS: After reviewing 7052 studies,
      we identified 67 screening programs: 24 nonintegrated; 41 programs integrated in
      a variety of health care facilities (e.g., general practitioner); and 2 programs
      with both integrated and nonintegrated strategies. Together, these programs
      identified approximately 25,700 HCV-infected individuals. In general, higher HCV
      prevalence was found in programs in countries with intermediate to high HCV
      prevalence, in psychiatric clinics, and in programs that used a prescreening
      selection based on HCV risk factors. Only 6 programs used a comparison group for
      evaluation purposes, and 1 program used theory about effective promotion for
      screening. Comparison of the programs and their effectiveness was hampered by
      lack of reported data on program characteristics, clinical follow-up, and type of
      diagnostic test. CONCLUSIONS: A prescreening selection based on risk factors can
      increase the efficiency of screening in low-prevalence populations, and we need
      programs with comparison groups to evaluate effectiveness. Also, program
      characteristics such as type of diagnostic test, screening uptake, and clinical
      outcomes should be reported systematically.

PMID- 24450801
TI  - Effect of salinity on the concentrations of radioisotopes in the aquatic
      environment of a hypersaline coastal lagoon.
AB  - Research of the effect of salinity on the fate of radionuclides has been focused
      on seas or estuarine systems while there is almost no information on marine
      environments with a salinity higher than that of sea water. The hypersaline
      Bardawil lagoon is a concentration basin, with evaporation exceeding
      precipitation. This study presents the characteristics of some environmental
      factors including salinity and their influence on the distribution of natural and
      artificial radionuclides in different compartments of the lagoon. The
      concentrations of (238)U, (234)Th, (228)Ra and (137)Cs in sediments show some
      degree of dependency on the water's salinity. Migration of these radionuclides in
      the lagoon's sediments must take place from high salinity to low-salinity
      regions. Cluster analysis revealed the data structure for sediment by separating
      (137)Cs and (40)K from (232)Th, (226)Ra, and (234)Th and for sand by separating
      (40)K from the other radioisotopes. 

PMID- 24450802
TI  - Soyasaponins Ab and Bb prevent scopolamine-induced memory impairment in mice
      without the inhibition of acetylcholinesterase.
AB  - Soy (Glycine max, family Leguminosae), which contains isoflavones and saponins as
      main constituents, is known to exhibit memory-enhancing effects. Therefore, to
      investigate the role of soyasaponins in memory impairments, we isolated
      soyasaponins Ab (SA) and Bb (SB) from soybean and measured their protective
      effects against scopolamine-induced memory impairment in mice. SA and SB
      significantly prevented scopolamine-induced memory impairment in passive
      avoidance and Y-maze tasks. Compared to SA, SB rescued memory impairment more
      potently. Treatment with SB (10 mg/kg, p.o.) protected memory impairment in
      passive avoidance and Y-maze tasks to 97% (F = 68.10, P < 0.05) and 78% (F =
      35.57, P < 0.05) of untreated normal control level, respectively. SA and SB (10
      mg/kg) also rescued scopolamine-induced memory impairment in Morris water maze
      task (F = 14.51, P < 0.05). In addition, soyasaponins preserved brain-derived
      neurotrophic factor (BNDF) expression (F = 33.69, P < 0.05) and cAMP response
      element-binding (CREB) protein phosphorylation (F = 91.62, P < 0.05) in the
      hippocampus of scopolamine-treated mice. However, SA and SB did not inhibit
      acetylcholinesterase in vitro and ex vivo. On the basis of these findings, we
      suggest that soybean, particularly soyasaponins, may protect memory impairment by
      increasing BDNF expression and CREB phosphorylation. 

PMID- 24450803
TI  - Feature tracking compared with tissue tagging measurements of segmental strain by
      cardiovascular magnetic resonance.
AB  - BACKGROUND: Left ventricular segmental wall motion analysis is important for
      clinical decision making in cardiac diseases. Strain analysis with myocardial
      tissue tagging is the non-invasive gold standard for quantitative assessment,
      however, it is time-consuming. Cardiovascular magnetic resonance myocardial
      feature-tracking (CMR-FT) can rapidly perform strain analysis, because it can be
      employed with standard CMR cine-imaging. The aim is to validate segmental peak
      systolic circumferential strain (peak SCS) and time to peak systolic
      circumferential strain (T2P-SCS) analysed by CMR-FT against tissue tagging, and
      determine its intra and inter-observer variability. METHODS: Patients in whom
      both cine CMR and tissue tagging has been performed were selected. CMR-FT
      analysis was done using endocardial (CMR-FTendo) and mid-wall contours (CMR
      FTmid). The Intra Class Correlation Coefficient (ICC) and Pearson correlation
      were calculated. RESULTS: 10 healthy volunteers, 10 left bundle branch block
      (LBBB) and 10 hypertrophic cardiomyopathy patients were selected. With CMR-FT all
      480 segments were analyzable and with tissue tagging 464 segments.Significant
      differences in mean peak SCS values of the total study group were present between
      CMR-FTendo and tissue tagging (-23.8 +/- 9.9% vs -13.4 +/- 3.3%, p<0.001).
      Differences were smaller between CMR-FTmid and tissue tagging (-16.4 +/- 6.1% vs 
      13.4 +/- 3.3%, p=0.001). The ICC of the mean peak SCS of the total study group
      between CMR-FTendo and tissue tagging was low (0.19 (95%-CI-0.10-0.49), p=0.02).
      Comparable results were seen between CMR-FTmid and tissue tagging. In LBBB
      patients, mean T2P-SCS values measured with CMR-FTendo and CMR-FTmid were 418 +/-
      66 ms, 454 +/- 60 ms, which were longer than with tissue tagging, 376 +/- 55 ms,
      both p<0.05. ICC of the mean T2P-SCS between CMR-FTendo and tissue tagging was
      0.64 (95%-CI-0.36-0.81), p<0.001, this was better in the healthy volunteers and
      LBBB group, whereas the ICC between CMR-FTmid and tissue tagging was lower.The
      intra and inter-observer agreement of segmental peak SCS with CMR-FTmid was lower
      compared with tissue tagging; similar results were seen for segmental T2P-SCS.
      CONCLUSIONS: The intra and inter-observer agreement of segmental peak SCS and T2P
      SCS is substantially lower with CMR-FTmid compared with tissue tagging.
      Therefore, current segmental CMR-FTmid techniques are not yet applicable for
      clinical and research purposes.

PMID- 24450804
TI  - Galactaro delta-lactone isomerase: lactone isomerization by a member of the
      amidohydrolase superfamily.
AB  - Agrobacterium tumefaciens strain C58 can utilize d-galacturonate as a sole source
      of carbon via a pathway in which the first step is oxidation of d-galacturonate
      to D-galactaro-1,5-lactone. We have identified a novel enzyme, D-galactarolactone
      isomerase (GLI), that catalyzes the isomerizaton of D-galactaro-1,5-lactone to D
      galactaro-1,4-lactone. GLI, a member of the functionally diverse amidohydrolase
      superfamily, is a homologue of LigI that catalyzes the hydrolysis of 2-pyrone-4,6
      dicarboxylate in lignin degradation. The ability of GLI to catalyze lactone
      isomerization instead of hydrolysis can be explained by the absence of the
      general basic catalysis used by 2-pyrone-4,6-dicarboxylate lactonase.

PMID- 24450805
TI  - Peri-implant soft tissue and marginal bone adaptation on implant with non
      matching healing abutments: micro-CT analysis.
AB  - PURPOSE: To assess (i) the outcome of changing the horizontal-offset dimension on
      the peri-implant soft tissues and the crestal bone and (ii) the effect of
      different healing abutments (flared vs. straight) on the marginal peri-implant
      soft tissues and crestal bone. MATERIALS AND METHODS: Two-piece dental implants
      diameters of 3.5 and 4.5 mm were placed at least 1 mm subcrestal in five beagle
      dogs. Three different investigational groups: (i) 3.5-mm-diameter implant with
      narrow healing abutment (3.5N), (ii) 4.5-mm-diameter implant with narrow healing
      abutment (4.5N), and (iii) 3.5-mm-diameter implant with wide healing abutment
      (3.5W), were assessed. After 4 months of healing, the vertical distance from the
      marginal crestal bone (MB) to the implant shoulder (IS); the vertical distance
      from the IS to the first bone-to-implant contact; and the horizontal distance of
      bone ingrowth on the implant platform were measured with a high-resolution micro
      CT (Xradia MicroXCT-200 system). RESULTS: Implants with a narrow healing caps
      showed an interproximal MB located between 0 and 1 mm above the implant shoulder,
      while the 3.5W group exhibits a mean value -0.50 mm. As all implants in group
      3.5N presented a fBIC located at the level of the IS. For the 4.5N group, the
      mean fBIC-IS distance was -0.52 mm apically to the IS. For the 3.5WC group, the
      mean fBIC-IS distance was -1.42 mm. Horizontal bone apposition was only observed
      for the 3.5N group and the 4.5N group. CONCLUSION: The dimension of the
      horizontal offset would play a minimal role in reducing bone remodeling, whereas
      the configuration of the transmucosal component would directly influence marginal
      bone remodeling.

PMID- 24450806
TI  - Retraction.
AB  - "Surgical Management of Cesarean Scar Ectopic Pregnancy with Totally
      Extraperitoneal Hysterotomy via Transvaginal Approach" by Ying-Han Chen, Dan-Bo
      Wang, Peng Chen and Fang Ren.The above article, published online on 23 January
      2014 in Wiley Online Library as an accepted article (wileyonlinelibrary. com;
      doi/10.1111/aogs.12341/abstract), has been retracted by agreement between the
      authors, the journal Chief Editor, Professor Reynir Tomas Geirsson, and John
      Wiley & Sons Ltd. The retraction has been agreed due to prior publication of a
      substantially similar article in Fertility and Sterility
      (http://www.fertstert.org/article/S0015-0282(13)03170-1/abstract).

PMID- 24450807
TI  - Follicular papules and pustules of the central face in a 40-year-old man.

PMID- 24450809
TI  - Obituary: Professor Christopher Stanislaus Potten BSc, PhD, DSc 1940-2012.

PMID- 24450808
TI  - Integrative analysis of the microbiome and metabolome of the human intestinal
      mucosal surface reveals exquisite inter-relationships.
AB  - BACKGROUND: Consistent compositional shifts in the gut microbiota are observed in
      IBD and other chronic intestinal disorders and may contribute to pathogenesis.
      The identities of microbial biomolecular mechanisms and metabolic products
      responsible for disease phenotypes remain to be determined, as do the means by
      which such microbial functions may be therapeutically modified. RESULTS: The
      composition of the microbiota and metabolites in gut microbiome samples in 47
      subjects were determined. Samples were obtained by endoscopic mucosal lavage from
      the cecum and sigmoid colon regions, and each sample was sequenced using the 16S
      rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass
      spectroscopy. Spearman correlations were used to identify widespread,
      statistically significant microbial-metabolite relationships. Metagenomes for
      identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway
      modules for imputed genes were assigned using HUMAnN. The resulting metabolic
      pathway abundances were mostly concordant with metabolite data. Analysis of the
      metabolome-driven distribution of OTU phylogeny and function revealed clusters of
      clades that were both metabolically and metagenomically similar. CONCLUSIONS: The
      results suggest that microbes are syntropic with mucosal metabolome composition
      and therefore may be the source of and/or dependent upon gut epithelial
      metabolites. The consistent relationship between inferred metagenomic function
      and assayed metabolites suggests that metagenomic composition is predictive to a
      reasonable degree of microbial community metabolite pools. The finding that
      certain metabolites strongly correlate with microbial community structure raises
      the possibility of targeting metabolites for monitoring and/or therapeutically
      manipulating microbial community function in IBD and other chronic diseases.

PMID- 24450810
TI  - Cytometry in the brain: studying differentiation to diagnostic applications in
      brain disease and regeneration therapy.
AB  - During brain development, a population of uniform embryonic cells migrates and
      differentiates into a large number of neural phenotypes - origin of the enormous
      complexity of the adult nervous system. Processes of cell proliferation,
      differentiation and programmed death of no longer required cells, do not occur
      only during embryogenesis, but are also maintained during adulthood and are
      affected in neurodegenerative and neuropsychiatric disease states. As
      neurogenesis is an endogenous response to brain injury, visible as proliferation
      (of to this moment silent stem or progenitor cells), its further stimulation can
      present a treatment strategy in addition to stem cell transfer for cell
      regeneration therapy. Concise techniques for studying such events in vitro and in
      vivo permit understanding of underlying mechanisms. Detection of subtle
      physiological alterations in brain cell proliferation and neurogenesis can be
      explored, that occur during environmental stimulation, exercise and ageing. Here,
      we have collected achievements in the field of basic research on applications of
      cytometry, including automated imaging for quantification of morphological or
      fluorescence-based parameters in cell cultures, towards imaging of three
      dimensional brain architecture together with DNA content and proliferation data.
      Multi-parameter and more recently in vivo flow cytometry procedures, have been
      developed for quantification of phenotypic diversity and cell processes that
      occur during brain development as well as in adulthood, with importance for
      therapeutic approaches. 

PMID- 24450811
TI  - Correlation between terminal restriction fragments and flow-FISH measures in
      samples over wide range telomere lengths.
AB  - OBJECTIVES: Terminal restriction fragment (TRF) analysis of human telomeres was
      used to calibrate flow-fluorescence in situ hybridization (FF) measures of
      telomere lengths to expand the range of measures and increase power of resolution
      of our previously published protocol. TRF data used as the gold standard should
      be obtained by electrophoresis with suitable resolution applied to appropriately
      isolated genomic DNA. When we considered TRF attained by correct methods, we
      found our method to be insufficiently accurate, thus we have reviewed our
      previously published FF protocol to obtain the best coefficient of determination
      (r(2)) between our experimental results and valid TRF lengths. MATERIALS AND
      METHODS: Using human telomere-specific PNA probe, Cy5-OO-(CCCTAA)3 , we measured
      telomere lengths of continuous cell line and of peripheral blood lymphocytes by
      FF. We modified hybridization, stringency, negative control handling,
      stoichiometric DNA staining and telomere fluorescence assessment of the protocol.
      RESULTS: We realized a procedure with increased power of resolution, improved TRF
      versus FF r(2) values that allowed simultaneous analysis of DNA and telomere
      duplication. Notwithstanding multiple steps in formamide sampling, recovery was
      satisfactory. DISCUSSION: The reviewed FF protocol appeared at least as suitable
      as the TRF method. Measures obtained by TRF can be affected by chromosome end
      variability, DNA fragmentation, incomplete digestion and unsuitable
      electrophoresis. In contrast, the FF technique analyses telomeric sequences
      confined to preserved nuclei thus overcome most previous limitations. As yet,
      however, the FF telomere measure cannot be performed together with
      immunophenotyping and/or generation study by the dye dilution method.

PMID- 24450812
TI  - Expression pattern of Ngn3 in dairy goat testis and its function in promoting
      meiosis by upregulating Stra8.
AB  - OBJECTIVES: Ngn3 is a typical transcription factor and marker of differentiating
      spermatogonial stem cells (SSCs) in mouse, belonging to the basic helix-loop
      helix (bHLH) family. Its gene is specifically expressed in A type spermatogonia
      in mouse testis, thus plays a critical role in controlling differentiation of
      SSCs. However, roles of Ngn3 and its protein in dairy goat testis remain unknown.
      MATERIALS AND METHODS: Testis development and expression patterns of Ngn3 were
      analysed by immunofluorescence and quantitative reverse transcription-polymerase
      chain reaction (QRT-PCR) in the dairy goat. Furthermore, effects of its
      overexpression on male germline stem cells (mGSCs) were evaluated by QRT-PCR,
      immunofluorescence, luciferase reporter assay and western blotting. RESULTS:
      Revealed that Ngn3 was expressed more highly during puberty and in the adult than
      in testis of other ages. Overexpression of Ngn3 promoted expression of meiosis
      related gene Stra8 and stem-cell differentiation marker CD117, but suppressed
      expression of Plzf, a classical marker of SSCs. Furthermore, Ngn3 did not promote
      expression of Stra8 directly as shown in transcription and translation levels
      detected by luciferase reporter assay and western blotting. CONCLUSIONS: Taken
      together, these results suggest that Ngn3 plays an important role in
      spermatogenesis and that overexpression of Ngn3 can promote meiosis in testis of
      the dairy goat.

PMID- 24450813
TI  - Inhibition of osteogenic differentiation of mesenchymal stem cells by copper
      supplementation.
AB  - OBJECTIVES: Copper has been added to scaffolds when investigating bone repair, as
      an agent to promote vascularization; however, little is known concerning its
      effect on mesenchymal stem cells (MSCs), which are considered to be the origin of
      osteoblasts. In this study, we have aimed to elucidate effects of copper on
      osteogenic differentiation of MSCs. MATERIALS AND METHODS: Rat bone marrow MSCs
      (rBMSCs) were used as a model. Their viability was assessed by MTT assay and
      Roche's CASY cell counter test and calcium deposition was evaluated by staining
      with alizarin red S. Fluorescent phalloidin F-actin stain was used to evaluate
      cytoskeletal changes, protein expressions were investigated by western blotting
      and mRNA levels were analysed using Q-PCR. A rat model for ectopic bone formation
      was used to assess effects of copper on MSCs in vivo. RESULTS: Copper
      supplementation resulted in inhibition of osteogenesis of rBMSCs, along with
      reduction in expression of a number of osteogenic genes, alkaline phosphatase
      activity and formation of bone nodules. Cytoskeletal changes to cells during
      osteogenesis was inhibited by copper supplementation. In vivo study confirmed
      that copper could inhibit collagen formation whilst promoting angiogenesis.
      CONCLUSIONS: Our study demonstrated that copper inhibited osteogenic
      differentiation of rBMSCs in vitro. The findings caution appropriate use of
      copper and have laid a foundation for further research.

PMID- 24450814
TI  - Staying at work and living with MS: a qualitative study of the impact of a
      vocational rehabilitation intervention.
AB  - OBJECTIVE: This study examines the impact of a patient designed occupational
      therapy led vocational rehabilitation (VR) intervention on the experiences of
      people with multiple sclerosis (MS) who were experiencing work instability. We
      used qualitative in-depth interviews to gain insight into participants'
      experiences of the intervention and identify the aspects that were most helpful
      from the participants' perspectives. DESIGN: We conducted interviews with 19
      participants 2-8 weeks after the completion of their VR intervention. In these
      interviews, the participants were asked to describe the processes of the
      intervention and the influence of these on their work and MS. The interviews were
      transcribed verbatim and data analysis involved coding and the use of the
      constant comparative method to develop themes. RESULTS: We identified five major
      themes related to the impact of the intervention on "understanding my symptoms
      and their management in the workplace", "removing my anxieties", "understanding
      and influencing my employer", "managing my loss of confidence" and "having
      professional support". CONCLUSIONS: The VR intervention was valued by people with
      MS who felt that after the intervention they had a greater understanding of
      disease related, work related and personal factors that impacted on their ability
      to work and they were supported to manage these by a skilled professional. The
      themes identified in this study help gain insight into the participants'
      experience of the intervention and identify aspects that were most helpful from
      the participants' perspectives. This information could be used to inform further
      research and service development.

PMID- 24450815
TI  - A novel fluorescence in situ hybridization test for rapid pathogen identification
      in positive blood cultures.
AB  - A novel molecular beacon-based fluorescence in situ hybridization (FISH) test
      allowing for the identification of a wide range of bacterial pathogens directly
      in positive blood cultures (BCs) was evaluated with positive BCs of 152 patients.
      Depending on the Gram stain, either a Gram-negative or a Gram-positive panel was
      used. The time to result was 30 min, and the hands-on time was only 10 min. Seven
      per cent of the cultured microorganisms were not included in the FISH panels; the
      identification rate of those included was 95.2%. Overall, the FISH test enabled
      accurate pathogen identification in 88.2% of all cases analysed.

PMID- 24450819
TI  - Targeted temperature management after intracerebral hemorrhage (TTM-ICH):
      methodology of a prospective randomized clinical trial.
AB  - RATIONALE: Intracerebral hemorrhage causes 15% of strokes annually in the United
      States, and there is currently no effective therapy. AIMS AND HYPOTHESIS: This is
      a clinical trial designed to study the safety, feasibility, and efficacy of a
      protocol of targeted temperature management to moderate hypothermia in
      intracerebral hemorrhage patients. METHODS: The targeted temperature management
      after intracerebral hemorrhage trial is a prospective, single-center,
      interventional, randomized, parallel, two-arm (1:1) phase-II clinical trial with
      blinded end-point ascertainment. Intracerebral hemorrhage patients will be
      randomized within 18 h of symptom onset to either 72 h of targeted temperature
      management to moderate hypothermia (32-34 degrees C) followed by a controlled
      rewarming at of 0.05-0.1 degrees C per hour or 72 h of targeted temperature
      management to normothermia (36-37 degrees C) using endovascular or surface
      cooling. OUTCOMES: The primary outcome is the development of serious adverse
      events possibly and probably related to treatment. Secondary outcomes include in
      hospital neurological deterioration between day 0-7, in-hospital mortality,
      functional outcome measured by the modified Rankin scale at discharge and 90
      days, and effect of treatment allocation on cerebral edema and hematoma volume.
      DISCUSSION: Intracerebral hemorrhage remains the most severe form of stroke with
      limited options to improve survival. As the early resuscitation phase in the
      intensive care unit represents the greatest opportunity for impact on clinical
      outcome, it also appears to be the most promising window of opportunity to
      demonstrate a benefit when investigating aggressive treatments. CONCLUSION: More
      research of novel therapies to improve outcomes after intracerebral hemorrhage is
      desperately needed. The results of the targeted temperature management after
      intracerebral hemorrhage clinical trial may provide additional information on the
      applicability of targeted temperature management after intracerebral hemorrhage.

PMID- 24450820
TI  - Chemical bonding in aqueous ferrocyanide: experimental and theoretical X-ray
      spectroscopic study.
AB  - Resonant inelastic X-ray scattering (RIXS) and X-ray absorption (XA) experiments
      at the iron L- and nitrogen K-edge are combined with high-level first-principles
      restricted active space self-consistent field (RASSCF) calculations for a
      systematic investigation of the nature of the chemical bond in potassium
      ferrocyanide in aqueous solution. The atom- and site-specific RIXS excitations
      allow for direct observation of ligand-to-metal (Fe L-edge) and metal-to-ligand
      (N K-edge) charge-transfer bands and thereby evidence for strong sigma-donation
      and pi-backdonation. The effects are identified by comparing experimental and
      simulated spectra related to both the unoccupied and occupied molecular orbitals
      in solution. 

PMID- 24450821
TI  - Faecal incontinence: standardizing outcome measures.

PMID- 24450822
TI  - Biosensor medaka for monitoring intersex caused by estrogenic chemicals.
AB  - Estrogenic chemicals can induce intersex in fish species leading to disturbance
      of spermatogenesis and impairment of reproductive success. To overcome the
      shortcomings of conventional histopathological observation on intersex (low
      sensitivity, relatively poor accuracy, long experimental periods, as well as
      laborious and time-consuming), we generated a pMOSP1-EGFP transgenic medaka fish
      model. In this transgenic fish, the green fluorescence protein (GFP) reporter
      gene was derived by the regulatory elements of the OSP1 gene, which is a specific
      and sensitive molecular biomarker for indicating intersex occurrence in male
      medaka fish exposed to estrogenic chemicals. The transgenic GFP was faithfully
      expressed in ovaries and in testes with intersex, perfectly mimicking the
      expression pattern of endogenous OSP1. In intersex testis, the diameters of
      primary oocytes which could be distinguished by GFP fluorescence observation were
      as small as 10 MUm, lower than that (more than 20 MUm) which is observable by
      histopathology. Using the novel transgenic medaka fish, intersex was observed
      after 90-day exposure to 0.75 ng/L 17alpha-ethinyloestradiol (EE2) (0-90 dph),
      but only at concentrations of at least 1.38 ng/L EE2 by histopathology. An
      effectiveness of a short-term in vivo assay for screening estrogenic chemicals
      that can monitor intersex appearance at early sex developmental stage (about 30
      dph) in male medaka fish was also demonstrated by assessing the intersex
      induction of EE2, 17beta-estradiol and 4-nonylphenol. This newly developed assay
      provides an enhanced ability for screening and testing estrogenic chemicals with
      the potential to induce intersex and studying their biological impacts. 

PMID- 24450823
TI  - The methylisothiazolinone epidemic: Is the fire out or is Rome still burning?

PMID- 24450824
TI  - Fragrance allergy and quality of life - a case-control study.
AB  - BACKGROUND: Fragrance ingredients can cause contact allergy, which may affect
      quality of life (QoL). However, few studies have investigated this topic.
      OBJECTIVES: To investigate QoL life among subjects with a fragrance allergy as
      compared with other eczema patients. METHODS: A case-control survey was sent to
      subjects with a positive patch test reaction to a fragrance ingredient/marker (n
      = 550) and to a control group (n = 1100). It contained questions on eczema and
      the newly developed fragrance QoL index. Participants had been consecutively
      patch tested at Gentofte University Hospital (2000-2010). The response rate was
      65.7%. Information on patch test data was retrieved from the National Contact
      Dermatitis Database. RESULTS: An increase in impairment of QoL was observed in
      women with fragrance allergy as compared with the control group (p = 0.042),
      which was not found among men. Several factors played a significant role in
      impairment of QoL in women: (i) number of fragrance allergies, (ii) severity of
      the patch test reaction, (iii) age combined with recent diagnosis; and (iv)
      allergy to specific fragrance ingredients/markers. CONCLUSION: Fragrance-allergic
      subjects are just as affected in their QoL as other eczema patients. However,
      women, and in particular recently diagnosed young women, seem to be more impaired
      in their QoL than other eczema patients.

PMID- 24450825
TI  - Allergic contact dermatitis resulting from multiple colophonium-related allergen
      sources.

PMID- 24450826
TI  - Allergic contact cheilitis caused by polysilicone-15 (Parsol(r) SLX) in a lipcare
      balm.

PMID- 24450827
TI  - Allergic contact dermatitis caused by self-adhesive electrocardiography
      electrodes: a rare case with concomitant roles of nickel and acrylates.

PMID- 24450828
TI  - Systemic allergic dermatitis resulting from oral administration of chromium with
      a food supplement.

PMID- 24450829
TI  - Severe recurrence of drug rash with eosinophilia and systemic symptoms syndrome
      secondary to rifampicin patch testing in a human immunodeficiency virus-infected
      man.

PMID- 24450830
TI  - Social capital and adherence to cervical and breast cancer screening guidelines:
      a cross-sectional study in rural Crete.
AB  - Breast and cervical cancers are among the leading causes of female mortality. The
      reasons that make women adhere, or not, to screening guidelines are not only
      related to individual and health characteristics but are also placed in a wider
      social and cultural context. Social capital might facilitate the dissemination of
      relevant knowledge of and the adherence to cancer screening guidelines. This
      cross-sectional study explored the associations of individual-level social
      capital with breast and cervical cancer screening and the knowledge for the
      existence of relevant screening tests (Pap test and mammography) in the
      municipality of Gorgolaini, a rural area in Crete, Greece. A random sample of 131
      of the 592 women of the 2001 electoral register were invited to participate in
      the study and 125 completed the Social Capital Questionnaire and two questions on
      self-reported health knowledge and behaviour (participation rate 95.4%). Women
      were eligible to participate if they were aged 35-75, had lived in the area for
      the last 10 years and were of Greek origin. Multiple logistic regressions were
      performed to establish associations among each social capital factor (total,
      participation in the community, value of life, tolerance for diversity, feelings
      of safety, family/friends connections) and knowledge of and adherence to breast
      and cervical cancer screening guidelines after adjustment for confounders. Our
      results suggest that early detection of breast and cervical cancers may be
      facilitated when taking into account the social context of the population. 

PMID- 24450831
TI  - Status and prospects of liver cirrhosis treatment by using bone marrow-derived
      cells and mesenchymal cells.
AB  - In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for
      treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow
      obtained under general anesthesia and infused mononuclear cells from the
      peripheral vein. The clinical study expanded and we treated liver cirrhosis
      induced by HCV and HBV infection and alcohol consumption. We found that the ABMi
      therapy was effective for cirrhosis patients and now we are treating patients
      with combined HIV and HCV infection and with metabolic syndrome-induced liver
      cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be
      successfully treated by the ABMi therapy, we are conducting randomized
      multicenter clinical studies designated "Advanced medical technology B" for HCV
      related liver cirrhosis in Japan. On the basis of our clinical study, we
      developed a proof-of-concept showing that infusion of bone marrow cells (BMCs)
      improved liver fibrosis and sequentially activated proliferation of hepatic
      progenitor cells and hepatocytes, further promoting restoration of liver
      functions. To treat patients with severe forms of liver cirrhosis, we continued
      translational research to develop less invasive therapies by using mesenchymal
      stem cells derived from bone marrow. We obtained a small quantity of BMCs under
      local anesthesia and expanded them into mesenchymal stem cells that will then be
      used for treating cirrhosis. In this review, we present our strategy to apply the
      results of our laboratory research to clinical studies.

PMID- 24450832
TI  - Updating the evidence base on the operational costs of supplementary immunization
      activities for current and future accelerated disease control, elimination and
      eradication efforts.
AB  - BACKGROUND: To achieve globally or regionally defined accelerated disease
      control, elimination and eradication (ADC/E/E) goals against vaccine-preventable
      diseases requires complementing national routine immunization programs with
      intensive, time-limited, and targeted Supplementary Immunization Activities
      (SIAs). Many global and country-level SIA costing efforts have historically
      relied on what are now outdated benchmark figures. Mobilizing adequate resources
      for successful implementation of SIAs requires updated estimates of non-vaccine
      costs per target population. METHODS: This assessment updates the evidence base
      on the SIA operational costs through a review of literature between 1992 and
      2012, and an analysis of actual expenditures from 142 SIAs conducted between 2004
      and 2011 and documented in country immunization plans. These are complemented
      with an analysis of budgets from 31 SIAs conducted between 2006 and 2011 in order
      to assess the proportion of total SIA costs per person associated with various
      cost components. All results are presented in 2010 US dollars. RESULTS: Existing
      evidence indicate that average SIA operational costs were usually less than
      US$0.50 per person in 2010 dollars. However, the evidence is sparse, non
      standardized, and largely out of date. Average operational costs per person
      generated from our analysis of country immunization plans are consistently higher
      than published estimates, approaching US$1.00 for injectable vaccines. The
      results illustrate that the benchmarks often used to project needs underestimate
      the true costs of SIAs and the analysis suggests that SIA operational costs have
      been increasing over time in real terms. Our assessment also illustrates that
      operational costs vary across several dimensions. Variations in the actual costs
      of SIAs likely to reflect the extents to which economies of scale associated with
      campaign-based delivery can be attained, the underlying strength of the
      immunization program, sensitivities to the relative ease of vaccine
      administration (i.e. orally, or by injection), and differences in disease
      specific programmatic approaches. The assessment of SIA budgets by cost component
      illustrates that four cost drivers make up the largest proportion of costs across
      all vaccines: human resources, program management, social mobilization, and
      vehicles and transportation. These findings suggest that SIAs leverage existing
      health system infrastructure, reinforcing the fact that strong routine
      immunization programs are an important pre-requisite for achieving ADC/E/E goals.
      CONCLUSIONS: The results presented here will be useful for national and global
      level actors involved in planning, budgeting, resource mobilization, and
      financing of SIAs in order to create more realistic assessments of resource
      requirements for both existing ADC/E/E efforts as well as for new vaccines that
      may deploy a catch-up campaign-based delivery component. However, limitations of
      our analysis suggest a need to conduct further research into operational costs of
      SIAs. Understanding the changing face of delivery costs and cost structures for
      SIAs will continue to be critical to avoid funding gaps and in order to improve
      vaccination coverage, reduce health inequities, and achieve the ADC/E/E goals
      many of which have been endorsed by the World Health Assembly and are included in
      the Decade of Vaccines Global Vaccine Action Plan.

PMID- 24450835
TI  - Intracellular growth of Mycobacterium avium subspecies and global transcriptional
      responses in human macrophages after infection.
AB  - BACKGROUND: Mycobacterium avium subsp. avium (Maa) and M. avium subsp.
      hominissuis (Mah) are environmental mycobacteria and significant opportunistic
      pathogens. Mycobacterium avium infections in humans and pigs are mainly due to
      Mah. It is not known whether this is caused by a difference in virulence or
      difference in exposure to the two subspecies. The aim of the present study was to
      investigate the ability of the M. avium subspecies to replicate intracellularly
      and to characterise the gene expression program triggered by infection of human
      primary macrophages. RESULTS: All isolates were able to invade and persist within
      human macrophages. However, intracellular replication was only evident in cells
      infected with the two Maa isolates. Transcriptional responses to the isolates
      were characterized by upregulation of genes involved in apoptosis, immune- and
      inflammatory response, signal transduction and NF-kB signaling, cell
      proliferation and T-cell activation. Although similar pathways and networks were
      perturbed by the different isolates, the response to the Maa subspecies was
      exaggerated, and there was evidence of increased activation of type I and II
      interferon signaling pathways. CONCLUSION: Mycobacterium avium isolates of
      different genetic characteristics invaded monocytes and induced different degree
      of macrophage activation. Isolates of Maa were able to replicate intracellularly
      suggesting that differences in exposure, uptake or induction of adaptive immunity
      are more likely explanations for the difference in prevalence between M. avium
      subspecies.

PMID- 24450833
TI  - Recent developments in cell-based assays and stem cell technologies for botulinum
      neurotoxin research and drug discovery.
AB  - Botulinum neurotoxins (BoNTs) are exceptionally potent inhibitors of
      neurotransmission, causing muscle paralysis and respiratory failure associated
      with the disease botulism. Currently, no drugs are available to counter
      intracellular BoNT poisoning. To develop effective medical treatments, cell-based
      assays provide a valuable system to identify novel inhibitors in a time- and cost
      efficient manner. Consequently, cell-based systems including immortalized cells,
      primary neurons and stem cell-derived neurons have been established. Stem cell
      derived neurons are highly sensitive to BoNT intoxication and represent an ideal
      model to study the biological effects of BoNTs. Robust immunoassays are used to
      quantify BoNT activity and play a central role during inhibitor screening. In
      this review, we examine recent progress in physiologically relevant cell-based
      assays and high-throughput screening approaches for the identification of both
      direct and indirect BoNT inhibitors. 

PMID- 24450837
TI  - Comprehensive study of valuable lipophilic phytochemicals in wheat bran.
AB  - Wheat bran, the major side-stream generated in the milling of wheat grains in the
      production of white flour, contains significant quantities of carbohydrate and
      proteins. While not interfering with flour utilization, the bran could be
      considered as an important feedstock within a biorefinery concept. Wheat bran
      also contains some amounts of lipids that can be used as a source of valuable
      phytochemicals. Gas chromatography and mass spectrometry analysis of the lipid
      composition of destarched wheat bran demonstrated that the predominant lipids
      found in wheat bran were free fatty acids (ca. 40% of total lipids), followed by
      acylglycerols (40%). Additionally, important amounts of alkylresorcinols (13% of
      total lipids) and steroid compounds (hydrocarbons, ketones, free sterols, sterol
      glycosides, sterol esters, and sterol ferulates) (7% of total lipids) were also
      present among the lipids of wheat bran. The use of wheat bran as a valuable
      source of phytochemicals of interest in the context of a wheat bran biorefinery
      is discussed. 

PMID- 24450836
TI  - Tick capillary feeding for the study of proteins involved in tick-pathogen
      interactions as potential antigens for the control of tick infestation and
      pathogen infection.
AB  - BACKGROUND: Ticks represent a significant health risk to animals and humans due
      to the variety of pathogens they can transmit during feeding. The traditional use
      of chemicals to control ticks has serious drawbacks, including the selection of
      acaricide-resistant ticks and environmental contamination with chemical residues.
      Vaccination with the tick midgut antigen BM86 was shown to be a good alternative
      for cattle tick control. However, results vary considerably between tick species
      and geographic location. Therefore, new antigens are required for the development
      of vaccines controlling both tick infestations and pathogen
      infection/transmission. Tick proteins involved in tick-pathogen interactions may
      provide good candidate protective antigens for these vaccines, but appropriate
      screening procedures are needed to select the best candidates. METHODS: In this
      study, we selected proteins involved in tick-Anaplasma (Subolesin and SILK) and
      tick-Babesia (TROSPA) interactions and used in vitro capillary feeding to
      characterize their potential as antigens for the control of cattle tick
      infestations and infection with Anaplasma marginale and Babesia bigemina.
      Purified rabbit polyclonal antibodies were generated against recombinant SUB,
      SILK and TROSPA and added to uninfected or infected bovine blood to capillary
      feed female Rhipicephalus (Boophilus) microplus ticks. Tick weight, oviposition
      and pathogen DNA levels were determined in treated and control ticks. RESULTS:
      The specificity of purified rabbit polyclonal antibodies against tick recombinant
      proteins was confirmed by Western blot and against native proteins in tick cell
      lines and tick tissues using immunofluorescence. Capillary-fed ticks ingested
      antibodies added to the blood meal and the effect of these antibodies on tick
      weight and oviposition was shown. However, no effect was observed on pathogen DNA
      levels. CONCLUSIONS: These results highlighted the advantages and some of the
      disadvantages of in vitro tick capillary feeding for the characterization of
      candidate tick protective antigens. While an effect on tick weight and
      oviposition was observed, the effect on pathogen levels was not evident probably
      due to high tick-to-tick variations among other factors. Nevertheless, these
      results together with previous results of RNA interference functional studies
      suggest that these proteins are good candidate vaccine antigens for the control
      of R. microplus infestations and infection with A. marginale and B. bigemina.

PMID- 24450838
TI  - Misdiagnosed amoebic colitis leading to severe dysentery and necrotizing colitis-
      report of a case and review of the literature.
AB  - We present a case of amoebic colitis, misdiagnosed as inflammatory bowel disease
      and treated with corticosteroids, leading to severe necrotizing enterocolitis. We
      review the literature on the epidemiology, pathogenesis, diagnosis, and treatment
      of amoebic dysentery, with special emphasis on the association between
      immunosuppressive treatment and the development of severe invasive amoebiasis.

PMID- 24450839
TI  - Pneumocystis jirovecii pneumonia in HIV-negative patients: a prospective study
      with focus on immunosuppressive drugs and markers of immune impairment.
AB  - Pneumocystis jirovecii pneumonia (PCP) is emerging in HIV-negative patients, for
      whom the prognosis is significantly worse than in HIV-infected patients and risk
      factors are poorly characterized. We performed an observational, multi-centre,
      prospective study of 56 consecutive cases of documented PCP in HIV-negative
      patients, and found that: (1) the main underlying conditions were haematological
      malignancies (43%), solid tumours (25%), inflammatory diseases (20%), and solid
      organ transplantation (7%); (2) most patients (80%) had received prolonged
      corticosteroids, with a mean daily dose of 47.3 +/- 32.8 mg equivalent prednisone
      when PCP was diagnosed, and a mean cumulative dose of 5807 +/- 5048 mg over the
      last 12 months; and (3) the median CD4 cell count was 0.12 * 109/l (range 0.0
      1.42), with a median CD4/CD8 ratio of 1.32 (0.0-6.4). These findings may be used
      to better target PCP prophylaxis according to the level of risk and contribute to
      decrease the burden of PCP in HIV-negative patients.

PMID- 24450840
TI  - Novel approaches to tuberculosis prevention: DNA vaccines.
AB  - It is estimated that there are approximately eight million new cases of active
      tuberculosis (TB) worldwide annually. There is only 1 vaccine available for
      prevention: bacillus Calmette-Guerin (BCG). This has variable efficacy and is
      only protective for certain extrapulmonary TB cases in children, therefore new
      strategies for the creation of novel vaccines have emerged. One of the promising
      approaches is the DNA vaccine, used as a direct vaccination or as a prime-boost
      vaccine. This review describes the experimental data obtained during the design
      of DNA vaccines for TB.

PMID- 24450841
TI  - Vertebral osteomyelitis: retrospective review of 11 years of experience.
AB  - INTRODUCTION: Infectious vertebral osteomyelitis (VO) is a significant source of
      morbidity that can lead to chronic sequelae. The objectives of this study were to
      describe the clinical presentations and assess the outcomes of VO. METHODS: A
      retrospective review of cases of VO admitted to an inpatient service between 1
      January 2000 and 31 March 2012 was carried out. Cases had evidence of VO by
      clinical syndrome, imaging, histopathology, and/or microbiology. Outcomes
      assessed were implantation of prosthetic material for stabilization, hospital
      readmission for management of VO, repeat surgical intervention, and additional or
      prolonged courses of antibiotics. RESULTS: Of 117 VO cases, a causative organism
      was identified in the majority (88.0%). Staphylococcus aureus was the most common
      organism isolated, followed by Streptococcus species. The most common infection
      site was the lumbar spine (55.5%). Surgical intervention was required in 81.2% of
      cases. Infections involving the lumbar vertebrae were associated with a higher
      risk of all 4 outcomes. Individuals with methicillin-resistant S. aureus
      infection were more likely to require a readmission for management of VO (odds
      ratio (OR) 3.94, 95% confidence interval (CI) 1.25-12.42). Individuals with
      lumbar infections were more likely to require additional antibiotics (OR 4.08,
      95% CI 1.34-12.40) and more likely to require readmission (OR 8.29, 95% CI 1.84
      37.33) for management of VO. An early infectious disease consultation was
      associated with a decreased risk for additional antibiotics (OR 0.30, 95% CI 0.11
      0.83). CONCLUSIONS: VO was frequently caused by S. aureus or Streptococcus
      species. Most cases required surgical intervention. An early infectious disease
      consult ensured a more appropriate antibiotic course.

PMID- 24450842
TI  - Disseminated cryptococcosis, invasive aspergillosis, and mucormycosis in a
      patient treated with alemtuzumab for chronic lymphocytic leukaemia.
AB  - We report the case of a 42-y-old man treated with alemtuzumab for chronic
      lymphocytic leukaemia, who developed 3 successive deep fungal infections. Despite
      being treated with liposomal amphotericin B and 5-flucytosine for disseminated
      cryptococcosis, he developed pulmonary invasive aspergillosis, followed by
      pulmonary mucormycosis. Several deep fungal infections may occur in association
      in an immunocompromised host after treatment with alemtuzumab.

PMID- 24450843
TI  - Outbreaks of methicillin-resistant Staphylococcus aureus among staff and dogs in
      Swedish small animal hospitals.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) was found in a dog for the
      first time in Sweden in 2006. Between October 2006 and May 2007, MRSA was
      diagnosed in 7 more dogs that had been treated in 3 different small animal
      hospitals, located 150-200 km apart, in different counties of Sweden. Screening
      of the animal hospital staff and environment in these small animal hospitals
      showed 20 of 152 staff to be positive for MRSA, with rates between 2% and 18% in
      the different hospitals, while all 128 environmental samples were negative. All
      MRSA isolates from dogs and staff belonged to spa type t032, were Panton
      Valentine leukocidin (PVL)-negative, and had indistinguishable pulsed-field gel
      electrophoresis patterns, except for 2 isolates with closely related patterns. To
      our knowledge, this is the first report of multiple outbreaks of MRSA in dogs
      caused by the same strain within a short time frame, and appearing in a country
      with low prevalence of MRSA in both humans and dogs. This highlights the
      importance of infection control programs in animal hospitals and in animal health
      care. Awareness of MRSA as an occupational risk for veterinary personnel is
      essential.

PMID- 24450844
TI  - Reductions in intestinal Clostridiales precede the development of nosocomial
      Clostridium difficile infection.
AB  - BACKGROUND: Antimicrobial use is thought to suppress the intestinal microbiota,
      thereby impairing colonization resistance and allowing Clostridium difficile to
      infect the gut. Additional risk factors such as proton-pump inhibitors may also
      alter the intestinal microbiota and predispose patients to Clostridium difficile
      infection (CDI). This comparative metagenomic study investigates the relationship
      between epidemiologic exposures, intestinal bacterial populations and subsequent
      development of CDI in hospitalized patients. We performed a nested case-control
      study including 25 CDI cases and 25 matched controls. Fecal specimens collected
      prior to disease onset were evaluated by 16S rRNA gene amplification and
      pyrosequencing to determine the composition of the intestinal microbiota during
      the at-risk period. RESULTS: The diversity of the intestinal microbiota was
      significantly reduced prior to an episode of CDI. Sequences corresponding to the
      phylum Bacteroidetes and to the families Bacteroidaceae and Clostridiales
      Incertae Sedis XI were depleted in CDI patients compared to controls, whereas
      sequences corresponding to the family Enterococcaceae were enriched. In
      multivariable analyses, cephalosporin and fluoroquinolone use, as well as a
      decrease in the abundance of Clostridiales Incertae Sedis XI were significantly
      and independently associated with CDI development. CONCLUSIONS: This study shows
      that a reduction in the abundance of a specific bacterial family - Clostridiales
      Incertae Sedis XI - is associated with risk of nosocomial CDI and may represent a
      target for novel strategies to prevent this life-threatening infection.

PMID- 24450845
TI  - Analysis of the dimensions of the labial bone wall in the anterior maxilla: a
      cone-beam computed tomography study.
AB  - BACKGROUND: Immediate implant placement in extraction socket does not appear to
      prevent the resorption of the labial wall. It has been recommended that a minimal
      thickness of 1-2 mm of buccal bone should be available to preclude the resorption
      of the facial vertical dimension of the socket wall. OBJECTIVE: The aim was to
      determine the dimension of the facial buccal plate of bone in the anterior
      esthetic zone at different levels and relate it to immediate implant placement.
      MATERIALS AND METHODS: Seventy-three patients' cone-beam tomographic scans were
      included in the study (42 female and 31 male, mean age 39.6 years). The images
      were acquired using OnDemand software. The measurements taken included: 1.
      Distance between the CEJ and the alveolar crest. 2. The labial bone thickness at
      different levels in relation to alveolar crest: at 1, 2, and 4 mm. THE RESULTS:
      The measurements demonstrated that the distance between the CEJ and the crest was
      2.10 +/- 0.85 for the central and 2.09 +/- 0.72 for the lateral incisor. The
      measurement taken at M0 (crestal level) revealed that only 1% of the incisors
      showed a thick labial bone (1-2 mm) and 73% showed a thin bony wall (0.5-1 mm)
      and 25% showed very thin wall <0.5 mm. At the M1, 7% showed very thin bony wall
      and 86% showed a thin bony wall while only 6% exhibited a thick bony wall. The M2
      showed only 1% of very thin bony wall, and about 85% showed a thin bony wall and
      14% exhibited a thick bony level. The M4 demonstrated very thin bony wall and
      about 75% thin bony wall and 23% showed thick bony wall. Males showed
      statistically significantly higher mean distance between cemento-enamel junction
      and alveolar crest (CEJ-AC) than females at the central as well as lateral
      incisors. To obtain good results, meticulous preoperative analysis is
      recommended. Thus, to chose an adequate treatment approach, the utilization of
      CBCT is recommended.

PMID- 24450846
TI  - Staff burnout in paediatric oncology: new tools to facilitate the development and
      evaluation of effective interventions.
AB  - Working in paediatric oncology can be stressful, and staff may need support if
      they are to avoid burnout, but there is currently no evidence base to guide the
      development of interventions. As a significant barrier to addressing this gap is
      a lack of context specific research instruments, a project was undertaken to
      develop measures of the stressors and rewards experienced by staff. Measure
      development involved: (1) qualitative interviews with a purposive sample of
      paediatric oncology staff to develop an 'item pool' (n = 32); (2) selection of
      items for draft measures; (3) cognitive interviews (n = 7) to gather feedback on
      draft measures; (4) a survey of staff (n = 203) using the draft and comparator
      measures; (5) factor and Rasch analysis to determine the scaling properties of
      the measures; (6) an assessment of construct validity. As a result, the Work
      Stressors Scale - Paediatric Oncology (WSS-PO) and the Work Rewards Scale -
      Paediatric Oncology (WRS-PO) were created. Both measures have considerable
      content validity, and fulfil classical test theory requirements and Rasch model
      requirements for an interval level scale. These new measures can be used in
      research and clinical practice to investigate factors associated with burnout,
      and to facilitate and direct the development of staff interventions. 

PMID- 24450847
TI  - The contribution of drugs to lichen sclerosus.

PMID- 24450848
TI  - Successful external cephalic version does not confer a measurable increased risk
      of intrapartum cesarean section in modern obstetric practice.

PMID- 24450849
TI  - Therapeutic peptides in inflammatory bowel disease.
AB  - INTRODUCTION: Therapeutic peptides in inflammatory bowel diseases essentially
      comprise cytokines affecting immune response, growth factors and monoclonal
      antibodies directed against key targets of mucosal inflammation, in particular,
      tumor necrosis factor-a (TNF-a). The latter have revolutionized standard medical
      treatment which previously was restricted to mesalamine, corticosteroids or
      classical immunosuppressants. AREAS COVERED: We review current evidence of the
      use of the so-called biologicals, including the well-established TNF-a
      antagonists and novel peptides and monoclonal antibodies developed for these
      diseases. The focus is on controlled clinical trials and meta-analyses, if
      available. Limitations and biases of these studies are important but tend to be
      ignored. Safety is also an important issue with opportunistic infections and
      lymphoma as relevant risks. There is significant heterogeneity between different
      countries, guidelines and opinions within the scientific community regarding
      clinical indications, even apart from pharmacoeconomics and reimbursement. EXPERT
      OPINION: TNF blockers have greatly extended medical options in inflammatory bowel
      diseases. Their more or less extensive use in nearly all patients or only a few
      selected indications is a matter of debate. It proved difficult to reproduce this
      success with other antibody targets as well as with immunomodulatory cytokines
      and growth factors. The most promising novel peptide is vedolizumab, an antibody
      against alpha4beta7 integrin.

PMID- 24450850
TI  - Temperature-dependent properties of silver-poly(methylmethacrylate)
      nanocomposites synthesized by in-situ technique.
AB  - Ag/PMMA nanocomposites were successfully synthesized by in-situ technique.
      Transmission electron microscopy (TEM) images show that the particles are
      spherical in shape and their sizes are dependent on temperature. The smallest
      particle achieved high stability as indicated from Zeta sizer analysis. The red
      shift of surface plasmon resonance (SPR) indicated the increases of particle
      sizes. X-ray diffraction (XRD) patterns exhibit a two-phase (crystalline and
      amorphous) structure of Ag/PMMA nanocomposites. The complexation of Ag/PMMA
      nanocomposites was confirmed using Raman spectroscopy. Fourier transform infrared
      spectroscopy spectra confirmed that the bonding was dominantly influenced by the
      PMMA and DMF solution. Finally, thermogravimetric analysis (TGA) results indicate
      that the total weight loss increases as the temperature increases. 

PMID- 24450851
TI  - Selective optical response of hydrolytically stable stratified Si rugate mirrors
      to liquid infiltration.
AB  - Stratified optical filters with distinct spectral features and layered surface
      chemistry were prepared on silicon substrates with stepwise anodic porosification
      and thermal carbonization. The use of differing parameters for successive
      carbonization treatments enabled the production of hydrolytically stable porous
      silicon-based layered optical structures where the adsorption of water to the
      lower layer is inhibited. This enables selective shifting of reflectance bands by
      means of liquid infiltration. The merit of using thermal carbonization for
      creating layered functionality was demonstrated by comparing the hydrolytic
      stability resulting from this approach to other surface chemistries available for
      Si. The functionality of the stratified optical structures was demonstrated under
      water and ethanol infiltration, and changes in the adsorption properties after 9
      months of storage were evaluated. The changes observed in the structure were
      explained using simulations based on the transfer matrix method and the Bruggeman
      effective medium approximation. Scanning electron microscopy was used for imaging
      the morphology of the porous structure. Finally, the adaptability of the method
      for preparing complex structures was demonstrated by stacking superimposed rugate
      structures with several reflective bands. 

PMID- 24450852
TI  - Prostacyclin signaling boosts NADPH oxidase 4 in the endothelium promoting
      cytoprotection and angiogenesis.
AB  - AIMS: Prostacyclin (PGI2) that is released from the vascular endothelium plays an
      important role in vasodilatation and thrombo-resistance, and it has long been
      suspected to protect cell survival. How it does so has never been clear.
      Recently, it has been shown that the NADPH oxidase 4 (Nox4) improves endothelial
      cell functions and promotes angiogenesis in vivo, but it was not known how to
      boost Nox4 therapeutically to exploit its protective functions in the
      vasculature. Here, we identified such a stimulus. RESULTS: The selective and
      stable prostacyclin receptor (IP-R) agonist cicaprost increases the expression of
      Nox4 in human endothelial cells of several types, including endothelial
      progenitor cells. The elevation of cellular cyclic-AMP increased Nox4 expression
      and H2O2 production and prevented endothelial cell apoptosis. We delineate the
      intracellular signaling that promotes cytoprotection: Cicaprost acts via the IP
      R/protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element
      binding (CREB) protein pathway. Importantly, the up-regulation of Nox4 by
      cicaprost also enhanced endothelial cell proliferation, migration, and
      angiogenesis, with all effects being substantially decreased by Nox4 gene
      silencing. Finally, cicaprost enhanced the growth of blood vessels into
      subcutaneous sponges implanted in mice, an effect that was also blocked by Nox4
      gene silencing. INNOVATION: The prostacyclin analogue cicaprost induces Nox4 via
      IP receptor-cAMP/PKA/CREB pathway. The activation of this pathway protects
      endothelial cells and enhances pro-angiogenic activity both in vitro and in vivo.
      CONCLUSION: Prostacyclin promotes the up-regulation of Nox4 in endothelial cells,
      which opens up a novel strategy that protects and enhances endothelial cell
      functions in cardiovascular disease, such as repair after myocardial infarction
      or other ischemic conditions.

PMID- 24450856
TI  - Open data.

PMID- 24450855
TI  - AltitudeOmics: exercise-induced supraspinal fatigue is attenuated in healthy
      humans after acclimatization to high altitude.
AB  - AIMS: We asked whether acclimatization to chronic hypoxia (CH) attenuates the
      level of supraspinal fatigue that is observed after locomotor exercise in acute
      hypoxia (AH). METHODS: Seven recreationally active participants performed
      identical bouts of constant-load cycling (131 +/- 39 W, 10.1 +/- 1.4 min) on
      three occasions: (i) in normoxia (N, PI O2 , 147.1 mmHg); (ii) in AH (FI O2 ,
      0.105; PI O2 , 73.8 mmHg); and (iii) after 14 days in CH (5260 m; PI O2 , 75.7
      mmHg). Throughout trials, prefrontal-cortex tissue oxygenation and middle
      cerebral artery blood velocity (MCAV) were assessed using near-infrared
      spectroscopy and transcranial Doppler sonography. Pre- and post-exercise twitch
      responses to femoral nerve stimulation and transcranial magnetic stimulation were
      obtained to assess neuromuscular and corticospinal function. RESULTS: In AH,
      prefrontal oxygenation declined at rest (Delta7 +/- 5%) and end-exercise (Delta26
      +/- 13%) (P < 0.01); the degree of deoxygenation in AH was greater than N and CH
      (P < 0.05). The cerebral O2 delivery index (MCAV * Ca O2 ) was 19 +/- 14% lower
      during the final minute of exercise in AH compared to N (P = 0.013) and 20 +/-
      12% lower compared to CH (P = 0.040). Maximum voluntary and potentiated twitch
      force were decreased below baseline after exercise in AH and CH, but not N.
      Cortical voluntary activation decreased below baseline after exercise in AH
      (Delta11%, P = 0.014), but not CH (Delta6%, P = 0.174) or N (Delta4%, P = 0.298).
      A twofold greater increase in motor-evoked potential amplitude was evident after
      exercise in CH compared to AH and N. CONCLUSION: These data indicate that
      exacerbated supraspinal fatigue after exercise in AH is attenuated after 14 days
      of acclimatization to altitude. The reduced development of supraspinal fatigue in
      CH may have been attributable to increased corticospinal excitability, consequent
      to an increased cerebral O2 delivery.

PMID- 24450859
TI  - Choosing wisely--the politics and economics of labeling low-value services.
AB  - More than 40 medical specialties have identified "Choosing Wisely" lists of five
      overused or low-value services. But these services vary widely in potential
      impact on care and spending, and specialty societies often name other
      specialties' services as low value. 

PMID- 24450857
TI  - Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.
AB  - BACKGROUND: Patients with relapsed chronic lymphocytic leukemia (CLL) who have
      clinically significant coexisting medical conditions are less able to undergo
      standard chemotherapy. Effective therapies with acceptable side-effect profiles
      are needed for this patient population. METHODS: In this multicenter, randomized,
      double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and
      safety of idelalisib, an oral inhibitor of the delta isoform of
      phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab
      plus placebo. We randomly assigned 220 patients with decreased renal function,
      previous therapy-induced myelosuppression, or major coexisting illnesses to
      receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice
      daily. The primary end point was progression-free survival. At the first
      prespecified interim analysis, the study was stopped early on the recommendation
      of the data and safety monitoring board owing to overwhelming efficacy. RESULTS:
      The median progression-free survival was 5.5 months in the placebo group and was
      not reached in the idelalisib group (hazard ratio for progression or death in the
      idelalisib group, 0.15; P<0.001). Patients receiving idelalisib versus those
      receiving placebo had improved rates of overall response (81% vs. 13%; odds
      ratio, 29.92; P<0.001) and overall survival at 12 months (92% vs. 80%; hazard
      ratio for death, 0.28; P=0.02). Serious adverse events occurred in 40% of the
      patients receiving idelalisib and rituximab and in 35% of those receiving placebo
      and rituximab. CONCLUSIONS: The combination of idelalisib and rituximab, as
      compared with placebo and rituximab, significantly improved progression-free
      survival, response rate, and overall survival among patients with relapsed CLL
      who were less able to undergo chemotherapy. (Funded by Gilead; ClinicalTrials.gov
      number, NCT01539512.).

PMID- 24450858
TI  - PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma.
AB  - BACKGROUND: Phosphatidylinositol-3-kinase delta (PI3Kdelta) mediates B-cell
      receptor signaling and microenvironmental support signals that promote the growth
      and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an
      orally active selective PI3Kdelta inhibitor, showed antitumor activity in
      patients with previously treated indolent non-Hodgkin's lymphomas. METHODS: In
      this single-group, open-label, phase 2 study, 125 patients with indolent non
      Hodgkin's lymphomas who had not had a response to rituximab and an alkylating
      agent or had had a relapse within 6 months after receipt of those therapies were
      administered idelalisib, 150 mg twice daily, until the disease progressed or the
      patient withdrew from the study. The primary end point was the overall rate of
      response; secondary end points included the duration of response, progression
      free survival, and safety. RESULTS: The median age of the patients was 64 years
      (range, 33 to 87); patients had received a median of four prior therapies (range,
      2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular
      lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma
      (15), and lymphoplasmacytic lymphoma with or without Waldenstrom's
      macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6%
      meeting the criteria for a complete response. The median time to a response was
      1.9 months, the median duration of response was 12.5 months, and the median
      progression-free survival was 11 months. Similar response rates were observed
      across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were
      small for some categories. The most common adverse events of grade 3 or higher
      were neutropenia (in 27% of the patients), elevations in aminotransferase levels
      (in 13%), diarrhea (in 13%), and pneumonia (in 7%). CONCLUSIONS: In this single
      group study, idelalisib showed antitumor activity with an acceptable safety
      profile in patients with indolent non-Hodgkin's lymphoma who had received
      extensive prior treatment. (Funded by Gilead Sciences and others;
      ClinicalTrials.gov number, NCT01282424.).

PMID- 24450860
TI  - Preventing and controlling influenza with available interventions.

PMID- 24450861
TI  - The Three Axial Perineal Evaluation (TAPE) score: a new scoring system for
      comprehensive evaluation of pelvic floor function.
AB  - AIM: Abnormalities of one pelvic floor compartment are usually associated with
      anomalies in the other compartments. Therapies which specifically address one
      clinical problem may potentially adversely affect other pelvic floor activities.
      A new comprehensive holistic scoring system defining global pelvic function is
      presented. METHOD: A novel scoring system with a software program is presented
      expressing faecal, urinary and gynaecological functions as a geometric polygon
      based on symptom-specific questionnaires [the three axial pelvic evaluation
      (TAPE) score] where differences in overall geometric area vary from normal. After
      validation in healthy volunteers, its clinical performance was tested on patients
      with obstructed defaecation, genital prolapse and urinary/faecal incontinence
      treated by the stapled transanal rectal resection (STARR) procedure, colpo
      hysterectomy and sacral nerve modulation, respectively. The TAPE score was
      correlated with the Pelvic Floor Impact Questionnaire 7 quality of life score.
      RESULTS: There was good inter-observer variation and internal consistency between
      two observers recording the TAPE score in normal volunteers. In the STARR
      patients, constipation improved but the TAPE score was unchanged because of
      deterioration in other pelvic floor functions leading to an unchanged overall
      postoperative recorded quality of life. Conversely, incontinent patients treated
      with sacral nerve stimulation improved their function showing concomitant
      improvements in TAPE scores and quality of life indices. Similar correlative
      improvements were noted in patients undergoing hysterectomy for genital prolapse.
      CONCLUSION: The TAPE score defines the impact of symptom-specific treatments on
      the pelvic floor and may provide an opportunity for comparison of clinical data
      between units and in clinical trials of specific medical and surgical pelvic
      floor management.

PMID- 24450862
TI  - Geochemical and microbiological characteristics during in situ chemical oxidation
      and in situ bioremediation at a diesel contaminated site.
AB  - While in situ chemical oxidation with persulfate has seen wide commercial
      application, investigations into the impacts on groundwater characteristics,
      microbial communities and soil structure are limited. To better understand the
      interactions of persulfate with the subsurface and to determine the compatibility
      with further bioremediation, a pilot scale treatment at a diesel-contaminated
      location was performed consisting of two persulfate injection events followed by
      a single nutrient amendment. Groundwater parameters measured throughout the 225
      day experiment showed a significant decrease in pH and an increase in dissolved
      diesel and organic carbon within the treatment area. Molecular analysis of the
      microbial community size (16S rRNA gene) and alkane degradation capacity (alkB
      gene) by qPCR indicated a significant, yet temporary impact; while gene copy
      numbers initially decreased 1-2 orders of magnitude, they returned to baseline
      levels within 3 months of the first injection for both targets. Analysis of soil
      samples with sequential extraction showed irreversible oxidation of metal
      sulfides, thereby changing subsurface mineralogy and potentially mobilizing Fe,
      Cu, Pb, and Zn. Together, these results give insight into persulfate application
      in terms of risks and effective coupling with bioremediation. 

PMID- 24450864
TI  - Relative contribution of stoichiometry and mean coordination to the fragility of
      Ge-As-Se glass forming liquids.
AB  - The structural relaxation properties of 34 compositions of Ge-As-Se glass forming
      liquids are investigated by differential scanning calorimetry (DSC). The
      fragility index (m) and activation energies for enthalpy relaxation (Ea) exhibit
      universal trends with respect to stoichiometry and mean coordination (?r?),
      respectively. The liquid fragility which defines the full temperature dependence
      of the relaxation processes shows no well defined trend with respect to ?r? but
      instead is found to be closely determined by the excess or deficiency in selenium
      with respect to stoichiometry. The mean coordination on the other hand appears to
      be an accurate predictor of the activation energy near the glass transition where
      most constraints are still intact. No intermediate phase is observed in either
      case. These results emphasize that chemical effects rather than topological
      effects appear to control the wide ranging structural mobility of these glass
      forming liquids. The consequences of these findings in terms of the thermal
      stability of the corresponding glasses are discussed. It is similarly found that
      sub-Tg relaxation is controlled by stoichiometry rather than topology. 

PMID- 24450863
TI  - The Nicotiana attenuata GLA1 lipase controls the accumulation of Phytophthora
      parasitica-induced oxylipins and defensive secondary metabolites.
AB  - Nicotiana attenuata plants silenced in the expression of GLYCEROLIPASE A1 (ir
      gla1 plants) are compromised in the herbivore- and wound-induced accumulation of
      jasmonic acid (JA). However, these plants accumulate wild-type (WT) levels of JA
      and divinyl-ethers during Phytophthora parasitica infection. By profiling
      oxylipin-enriched fractions with targeted and untargeted liquid chromatography
      tandem time-of-flight mass spectrometry approaches, we demonstrate that the
      accumulation of 9-hydroxy-10E,12Z-octadecadienoic acid (9-OH-18:2) and additional
      C18 and C19 oxylipins is reduced by ca. 20-fold in P. parasitica-infected ir-gla1
      leaves compared with WT. This reduced accumulation of oxylipins was accompanied
      by a reduced accumulation of unsaturated free fatty acids and specific lysolipid
      species. Untargeted metabolic profiling of total leaf extracts showed that 87
      metabolites accumulated differentially in leaves of P. parasitica-infected ir
      gla1 plants with glycerolipids, hydroxylated-diterpene glycosides and
      phenylpropanoid derivatives accounting together for ca. 20% of these 87
      metabolites. Thus, P. parasitica-induced oxylipins may participate in the
      regulation of metabolic changes during infection. Together, the results
      demonstrate that GLA1 plays a distinct role in the production of oxylipins during
      biotic stress responses, supplying substrates for 9-OH-18:2 and additional C18
      and C19 oxylipin formation during P. parasitica infection, whereas supplying
      substrates for the biogenesis of JA during herbivory and mechanical wounding. 

PMID- 24450865
TI  - Factors influencing tobacco use treatment patterns among Vietnamese health care
      providers working in community health centers.
AB  - BACKGROUND: Almost half of adult men in Viet Nam are current smokers, a smoking
      prevalence that is the second highest among South East Asian countries (SEAC).
      Although Viet Nam has a strong public health delivery system, according to the
      2010 Global Adult Tobacco Survey, services to treat tobacco dependence are not
      readily available to smokers. The purpose of this study was to characterize
      current tobacco use treatment patterns among Vietnamese health care providers and
      factors influencing adherence to guideline recommended tobacco use screening and
      cessation interventions. METHODS: A cross sectional survey of 134 health care
      providers including physicians, nurses, midwives, physician assistants and
      pharmacists working in 23 community health centers in Viet Nam. RESULTS: 23% of
      providers reported screening patients for tobacco use, 33% offered advice to quit
      and less than 10% offered assistance to half or more of their patients in the
      past three months. Older age, attitudes, self-efficacy and normative beliefs were
      associated with screening for tobacco use. Normative beliefs were associated with
      offering advice to quit. However in the logistic regression analysis only
      normative beliefs remained significant for both screening and offering advice to
      quit. Over 90% of providers reported having never received training related to
      tobacco use treatment. Major barriers to treating tobacco use included lack of
      training, lack of referral resources and staff to support counseling, and lack of
      patient interest. CONCLUSIONS: Despite ratifying the FCTC, Viet Nam has not made
      progress in implementing policies and systems to ensure that smokers are
      receiving evidence-based treatment. This study suggests a need to change
      organizational norms through changes in national policies, training and local
      system-level changes that facilitate treatment.

PMID- 24450866
TI  - Schwannomas and their pathogenesis.
AB  - Schwannomas may occur spontaneously, or in the context of a familial tumor
      syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney's
      complex. Schwannomas have a variety of morphological appearances, but they behave
      as World Health Organization (WHO) grade I tumors, and only very rarely undergo
      malignant transformation. Central to the pathogenesis of these tumors is loss of
      function of merlin, either by direct genetic change involving the NF2 gene on
      chromosome 22 or secondarily to merlin inactivation. The genetic pathways and
      morphological features of schwannomas associated with different genetic syndromes
      will be discussed. Merlin has multiple functions, including within the nucleus
      and at the cell membrane, and this review summarizes our current understanding of
      the mechanisms by which merlin loss is involved in schwannoma pathogenesis,
      highlighting potential areas for therapeutic intervention. 

PMID- 24450867
TI  - Review of use of a new rapid real-time PCR, the Cepheid GeneXpert(r) (Xpert)
      CT/NG assay, for Chlamydia trachomatis and Neisseria gonorrhoeae: results for
      patients while in a clinical setting.
AB  - Rapid diagnostics for Chlamydia trachomatis and Neisseria gonorrhoeae are
      desirable so that patients can be treated while they are still in the clinic or
      doctor's office. The Cepheid GeneXpert((r)) (Xpert) CT/NG assay was US FDA
      cleared in December 2012. The assay is a rapid real-time PCR nucleic acid
      amplified test. The cartridge-based assay detects DNA of Chlamydia trachomatis
      and Neisseria gonorrhoeae. It is FDA-cleared for use in female endocervical
      swabs, patient-collected vaginal swabs and for female and male urine specimens
      from symptomatic and asymptomatic patients. It has demonstrated near-perfect
      sensitivity and specificity in urogenital specimens. The Xpert is a modular
      platform for testing samples directly from patients, which requires no hands-on
      manipulation from specimen loading until results are available. Results are
      provided in approximately 90 minutes. It has been graded by the FDA as moderately
      complex for Clinical Laboratory Improvement Amendments. Several publications have
      reported its promising use in clinical settings. 

PMID- 24450868
TI  - Gene expression profiling of mesenteric lymph nodes from sheep with natural
      scrapie.
AB  - BACKGROUND: Prion diseases are characterized by the accumulation of the
      pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system.
      Although prions multiply/accumulate in the lymph nodes without any detectable
      pathology, transcriptional changes in this tissue may reflect biological
      processes that contribute to the molecular pathogenesis of prion diseases. Little
      is known about the molecular processes that occur in the lymphoreticular system
      in early and late stages of prion disease. We performed a microarray-based study
      to identify genes that are differentially expressed at different disease stages
      in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA
      microarrays were used to identify gene-expression profiles in the early/middle
      (preclinical) and late (clinical) stages of the disease. RESULTS: In the clinical
      stage of the disease, we detected 105 genes that were differentially expressed
      (>=2-fold change in expression). Of these, 43 were upregulated and 62
      downregulated as compared with age-matched negative controls. Fewer genes (50)
      were differentially expressed in the preclinical stage of the disease. Gene
      Ontology enrichment analysis revealed that the differentially expressed genes
      were largely associated with the following terms: glycoprotein, extracellular
      region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of
      the annotated genes could be grouped into 3 specific signaling pathways: focal
      adhesion, PPAR signaling and ECM-receptor interaction. We discuss the
      relationship between the observed gene expression profiles and PrPSc deposition
      and the potential involvement in the pathogenesis of scrapie of 7 specific
      differentially expressed genes whose expression levels were confirmed by real
      time-PCR. CONCLUSIONS: The present findings identify new genes that may be
      involved in the pathogenesis of natural scrapie infection in the lymphoreticular
      system, and confirm previous reports describing scrapie-induced alterations in
      the expression of genes involved in protein misfolding, angiogenesis and the
      oxidative stress response. Further studies will be necessary to determine the
      role of these genes in prion replication, dissemination and in the response of
      the organism to this disease.

PMID- 24450869
TI  - Vaccination with recombinant Brugia malayi cystatin proteins alters worm
      migration, homing and final niche selection following a subcutaneous challenge of
      Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae.
AB  - BACKGROUND: Cysteine protease inhibitors of Brugia malayi have been ascribed to
      be involved in parasite development as well as to immunomodulate the host's
      immune response. In Onchocerca volvulus, Onchocystatin has been shown to induce
      partial protection in the mouse diffusion chamber vaccination model. In the
      present study we investigated the impact of vaccination with recombinant Bm-CPI-1
      and Bm-CPI-2 proteins on protection against a subcutaneous challenge of B. malayi
      third stage larvae in gerbils. FINDINGS: Vaccination with E. coli derived
      recombinant B. malayi cysteine protease inhibitors (Bm-CPI-1 or -2) did not
      confer protection against B. malayi L3 challenge infection in gerbils but altered
      the homing of a significant number of adult worms from the lymphatics to the
      heart and lungs. CONCLUSION: Bm-CPI vaccination-induced alteration in worm
      migration is consistent with our previous observations in gerbils vaccinated with
      B. pahangi excretory-secretory (ES) proteins, which resulted in delayed migration
      of the L3s and altered the final location of adult worms. Similar observations
      have also been made in dogs vaccinated with Ancylostoma caninum proteins; an
      increased number of worms were recovered in the colon and not the expected small
      intestine. A change in the final niche was also reported in immune versus non
      immune hosts of two other gut dwelling nematodes. Vaccination induced alteration
      of the parasite's final homing might be a rare or a common phenomenon, which
      unfortunately is rarely recorded. The reason for the alteration in the final
      niche selection by adult nematode worms following vaccination is unknown and
      necessitates further investigation.

PMID- 24450870
TI  - Maternal fat supplementation during late pregnancy and lactation influences the
      development of hepatic steatosis in offspring depending on the fat source.
AB  - In this study we investigate the effects of maternal supplementation with
      different fat sources (margarine, olive oil, or butter) during pregnancy and
      lactation on offspring metabolic health in adulthood and under obesogenic
      conditions. In adulthood and under a high-fat (HF) diet, the margarine group
      showed lower body fat content than the butter group and was also protected
      against the increase in hepatic lipid content occurring in the other groups,
      whereas the butter group showed signs of more advanced hepatic steatosis. Under
      an HF diet, all fat-supplemented animals showed greater hepatic expression levels
      of fatty acid oxidation-related genes compared to their normal-fat diet
      counterparts, with higher levels in the margarine group. Under these conditions,
      the margarine group also showed higher white adipose tissue mRNA levels of
      adipogenic genes than the other fat-supplemented groups. Thus, compared to other
      fat sources, offspring from margarine-supplemented dams seem to be more protected
      from metabolic alterations related to the HF diet, particularly concerning
      hepatic fat accumulation. 

PMID- 24450871
TI  - Enrichment of lung microbiome with supraglottic taxa is associated with increased
      pulmonary inflammation.
AB  - BACKGROUND: The lung microbiome of healthy individuals frequently harbors oral
      organisms. Despite evidence that microaspiration is commonly associated with
      smoking-related lung diseases, the effects of lung microbiome enrichment with
      upper airway taxa on inflammation has not been studied. We hypothesize that the
      presence of oral microorganisms in the lung microbiome is associated with
      enhanced pulmonary inflammation. To test this, we sampled bronchoalveolar lavage
      (BAL) from the lower airways of 29 asymptomatic subjects (nine never-smokers, 14
      former-smokers, and six current-smokers). We quantified, amplified, and sequenced
      16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary
      inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes, and
      neutrophils. RESULTS: BAL had lower total 16S than supraglottic samples and
      higher than saline background. Bacterial communities in the lower airway
      clustered in two distinct groups that we designated as pneumotypes. The rRNA gene
      concentration and microbial community of the first pneumotype was similar to that
      of the saline background. The second pneumotype had higher rRNA gene
      concentration and higher relative abundance of supraglottic-characteristic taxa
      (SCT), such as Veillonella and Prevotella, and we called it pneumotypeSCT.
      Smoking had no effect on pneumotype allocation, alpha, or beta diversity.
      PneumotypeSCT was associated with higher BAL lymphocyte-count (P= 0.007), BAL
      neutrophil-count (P= 0.034), and eNO (P= 0.022). CONCLUSION: A pneumotype with
      high relative abundance of supraglottic-characteristic taxa is associated with
      enhanced subclinical lung inflammation.

PMID- 24450873
TI  - Esthetic outcome of single implant crowns following type 1 and type 3 implant
      placement: a systematic review.
AB  - OBJECTIVE: The aim of the current review was to systematically appraise the
      esthetic outcome of soft tissue around single implant crowns following type 1 and
      type 3 implants placement in published dental literature. MATERIALS AND METHODS:
      A PubMed, Embase, and the Cochrane Central Register of Controlled Trials search
      up to March 2013 was conducted for articles published in the dental literature
      and limited to human trials with no language restricted. Furthermore, the
      reference lists of related articles were systematically screened, and additional
      manual searches were also performed. The primary outcome was pink esthetics score
      (PES). RESULTS: The electronic search in the database of PubMed, Embase, and the
      Cohrane Central Register of Controlled Trials resulted in the identification of
      463 titles. These titles were initially screened by the two independent reviewers
      for possible inclusion. Screening the abstracts and titles led to 28 articles for
      future full-text consideration. From these articles, 18 studies were excluded.
      Manual search identified one article. After quality assessment, eight studies
      were included in this review. This review showed that no significant difference
      of PES index could be found between type 1 and type 3 implant placement.
      CONCLUSION: According to the current evidence, short-term esthetic outcomes of
      peri-implant soft tissue did not show significant difference following type 1 and
      type 3 implants placement with well-selected patients. However, caution should be
      taken for clinicians to extrapolate this result to all types of patients, as more
      randomized clinical trials are needed for long-term soft-tissue esthetic outcome
      in patients with high esthetic risk following type 1 implant placement. PES
      frequency, peri-implant condition and other risk factors for peri-implantitis are
      recommended to be reported for future studies.

PMID- 24450874
TI  - Data collection and sampling in qualitative research: does size matter?

PMID- 24450876
TI  - Twitter and nursing research: how diffusion of innovation theory can help uptake.

PMID- 24450877
TI  - Gene delivery strategies for the treatment of mucopolysaccharidoses.
AB  - INTRODUCTION: Mucopolysaccharidosis (MPS) disorders are genetic diseases caused
      by deficiencies in the lysosomal enzymes responsible for the degradation of
      glycosaminoglycans. Current treatments are not able to correct all disease
      symptoms and are not available for all MPS types, which makes gene therapy
      especially relevant. Multiple gene therapy approaches have been tested for
      different types of MPS, and our aim in this study is to critically analyze each
      of them. AREAS COVERED: In this review, we have included the major studies that
      describe the use of adeno-associated retroviral and lentiviral vectors, as well
      as relevant non-viral approaches for MPS disorders. EXPERT OPINION: Some
      protocols such as the use of adeno-associated vectors and lentiviral vectors are
      approaching the clinic for these disorders and, along with combined approaches,
      seem to be the future of gene therapy for MPS.

PMID- 24450878
TI  - Association between unmet needs and quality of life in hospitalised cancer
      patients no longer receiving anti-cancer treatment.
AB  - Assessing the quality of life and unmet needs of cancer patients is an integral
      part of palliative care. This cross-sectional study sought to determine whether
      there is an association between quality of life and unmet needs, anxiety and
      depression in cancer patients who are no longer receiving anti-cancer treatment.
      The sample consisted of 93 patients from the oncology department at the
      University Hospital in Ostrava for whom further cancer treatment had been
      terminated as ineffective in halting the progression of their cancer. The
      European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire (EORTC QLQ-C30), the Patient Needs Assessment in Palliative Care
      (PNAP) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) were
      used to collect data. The overall quality of life score was quite low at 46. Most
      unmet needs were defined in terms of physical, psychological or spiritual needs.
      Correlations were found between impaired quality of life and lower Karnofsky
      scores (r = 0.50); increased physical (r = 0.52), psychological (r = 0.44) and
      spiritual (r = 0.36) needs; and higher levels of anxiety (r = -0.30) and
      depression (r = -0.68). Effective management of patients' physical (pain, fatigue
      and depression), psychological and spiritual needs may improve their quality of
      life. 

PMID- 24450879
TI  - Daily blood feeding rhythms of laboratory-reared North American Culex pipiens.
AB  - BACKGROUND: Blood feeding by free-living insect vectors of disease is rhythmic
      and can be used to predict when infectious bites will occur. These daily rhythms
      can also be targeted by control measures, as in insecticide-treated nets. Culex
      pipiens form pipiens and C.p. f. molestus are two members of the Culex pipiens
      assemblage and vectors of West Nile Virus throughout North America. Although
      Culex species vector human pathogens and parasites, the daily blood feeding
      rhythms of C.p. f. molestus, to our knowledge, have not been studied. We
      described and compared the daily blood feeding rhythms of three laboratory-reared
      populations of Culex pipiens, one of which has confirmed molestus ancestry. We
      also examined the plasticity of blood feeding time for these three populations.
      RESULTS: For most (>70%) C.p. f. pipiens and C.p. f. molestus collected from
      metropolitan Chicago, IL, blood feeding took place during scotophase. Peak blood
      feeding occurred in mid-scotophase, 3-6 hours after lights off. For C.p. f.
      pipiens originating from Pennsylvania, most mosquitoes (> 90%) blood fed during
      late photophase and early scotophase. C.p. f. molestus denied a blood meal during
      scotophase were less likely to blood feed during early photophase (< 20%) than
      were C.p. f. pipiens from Chicago (> 50%). C.p. f. pipiens from Pennsylvania were
      capable of feeding readily at any hour of photo- or scotophase. CONCLUSIONS:
      Daily blood feeding rhythms of C.p. f. molestus are similar to those of C.p. f.
      pipiens, particularly when populations originate from the same geographic region.
      However, the timing of blood feeding is more flexible for C.p. f. pipiens
      populations relative to C.p. f. molestus.

PMID- 24450880
TI  - The major G-quadruplex formed in the human BCL-2 proximal promoter adopts a
      parallel structure with a 13-nt loop in K+ solution.
AB  - The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter
      that has been shown to be critically involved in the regulation of BCL-2 gene
      expression. Inhibition of BCL-2 expression can decrease cellular proliferation
      and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex
      formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4
      quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal
      loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V,
      unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G
      runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears
      to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded
      structures with two 1-nt loops and one variable-length middle loop are found to
      be prevalent in the promoter G-quadruplexes; the variable middle loop is
      suggested to determine the specific overall structure and potential ligand
      recognition site. A limit of 7 nt in loop length is used in all quadruplex
      predicting software. Thus, the formation and high stability of the 1245G4
      quadruplex with a 13-nt loop is significant. The presence of two distinct
      interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is
      intriguing, suggesting a novel mechanism for gene transcriptional regulation and
      ligand modulation. 

PMID- 24450881
TI  - Intraocular pressure, specular microscopy, and prostaglandin E2 concentration in
      dogs with mature and hypermature cataract.
AB  - This study aimed to evaluate and correlate intraocular pressure (IOP),
      endothelial cell density (CD), and hexagonality (HEX), and the aqueous humor
      prostaglandin E2 (PGE2 ) concentration in dogs with mature (MG, n = 8) and
      hypermature (HG, n = 8) cataracts. Eight laboratory beagles with no ocular
      abnormalities were included as a control group (CG). The IOP was measured using a
      digital applanation tonometer. Noncontact specular microscopy was used to
      evaluate CD and HEX. Samples of aqueous humor were used to determine
      prostaglandin E2 concentration using enzyme-linked immunoassay. Data were
      compared by anova and Bonferroni's multiple comparison test, and possible
      correlations among the PGE2 aqueous concentration and corneal endothelium cell
      parameters were assessed by Person's test (P < 0.05). Average values of IOP (P =
      0.45) and CD (P = 0.39) were not significantly different between MG, HM, and CG.
      Average values of HEX were lower, and PGE2 concentration was increased in the MG
      and HG in comparison with CG (P < 0.05); however, such parameters did not change
      significantly between MG and HG (P > 0.05). PGE2 values did not correlate with
      IOP, CD, and HEX in any group (P > 0.05). Although there were a small number of
      dogs studied, our results demonstrated that cataract progression from mature to
      hypermature did not have a significant change in PGE2 aqueous concentration, IOP,
      corneal endothelial cell count, or morphology. In addition, PGE2 concentration
      was not correlated with parameters of the corneal endothelium or IOP in dogs with
      mature or hypermature cataracts.

PMID- 24450882
TI  - Increased collagen III in culled chicken meat after feeding dietary wood charcoal
      and vinegar contributes to palatability and tenderness.
AB  - We comprehensively evaluated meat quality in chickens fed a diet consisting of
      wood charcoal and vinegar (WCV) using food scientific and histological
      approaches. In culled hens, lipid and fatty acid in Musculus semimembranosus,
      cooking loss and sensory tests of whole thigh meat, and meat texture of breast
      meat were observed. In male broilers, cross section of M. semimembranosus was
      used for observations on muscle area, perimysium, non-collagen total protein and
      total collagen content, and anti-collagen I and III reactions. In frozen male
      broilers, conventional morphology of M. semimembranosus as well as chicken anti
      collagen III reaction to selected muscles of thigh meat and breast meat were
      compared between the control and WCV-fed birds. Increased lipid and fatty acids,
      decreased cooking loss, high score in total evaluation for sensory test of thigh
      meat, and decreased meat texture values were observed for culled hens fed WCV.
      The higher values of muscle area, total collagen and collagen III were observed
      for broilers fed WCV. No perimysium collapse for M. semitendinosus or increased
      collagen III reactions of M. tensor fasciae latae, the flexor muscle group and M.
      pectoralis superficialis were observed for frozen muscles in the WCV group. These
      total results suggest that WCV produces palatable and tender meat by increasing
      collagen III. 

PMID- 24450883
TI  - Boron-dipyrromethene based reversible and reusable selective chemosensor for
      fluoride detection.
AB  - We synthesized benzimidazole substituted boron-dipyrromethene 1 (BODIPY 1) by
      treating 3,5-diformyl BODIPY 2 with o-phenylenediamine under mild acid catalyzed
      conditions and characterized by using various spectroscopic techniques. The X-ray
      structure analysis revealed that the benzimidazole NH group is involved in
      intramolecular hydrogen bonding with fluoride atoms which resulted in a coplanar
      geometry between BODIPY and benzimidazole moiety. The presence of benzimidazole
      moiety at 3-position of BODIPY siginificantly altered the electronic properties,
      which is clearly evident in bathochromic shifts of absorption and fluorescence
      bands, improved quantum yields, increased lifetimes compared to BODIPY 2. The
      anion binding studies indicated that BODIPY 1 showed remarkable selectivity and
      specificity toward F(-) ion over other anions. Addition of F(-) ion to BODIPY 1
      resulted in quenching of fluorescence accompanied by a visual detectable color
      change from fluorescent pink to nonfluorescent blue. The recognition mechanism is
      attributed to a fluoride-triggered disruption of the hydrogen bonding between
      BODIPY and benzimidazole moieties leading to (i) noncoplanar geometry between
      BODIPY and benzimidazole units and (ii) operation of photoinduced electron
      transfer (PET) from benzimidazole moiety to BODIPY unit causing quenching of
      fluorescence. Interestingly, when we titrated the nonfluorescent blue 1-F(-)
      solution with TFA resulted in a significant enhancement of fluorescence intensity
      (15-fold) because the PET quenching is prevented due to protonation of
      benzimidazole group. Furthermore, the reversibility and reusability of sensor 1
      for the detection of F(-) ion was tested for six cycles indicating the sensor 1
      is stable and can be used in reversible manner. 

PMID- 24450884
TI  - Membrane-bound CYB5R3 is a common effector of nutritional and oxidative stress
      response through FOXO3a and Nrf2.
AB  - AIMS: Membrane-bound CYB5R3 deficiency in humans causes recessive hereditary
      methaemoglobinaemia (RHM), an incurable disease that is characterized by severe
      neurological disorders. CYB5R3 encodes for NADH-dependent redox enzyme that
      contributes to metabolic homeostasis and stress protection; however, how it is
      involved in the neurological pathology of RHM remains unknown. Here, the role and
      transcriptional regulation of CYB5R3 was studied under nutritional and oxidative
      stress. RESULTS: CYB5R3-deficient cells exhibited a decrease of the NAD(+)/NADH
      ratio, mitochondrial respiration rate, ATP production, and mitochondrial electron
      transport chain activities, which were associated with higher sensitivity to
      oxidative stress, and an increase in senescence-associated beta-galactosidase
      activity. Overexpression of either forkhead box class O 3a (FOXO3a) or nuclear
      factor (erythroid-derived 2)-like2 (Nrf2) was associated with increased CYB5R3
      levels, and genetic ablation of Nrf2 resulted in lower CYB5R3 expression. The
      presence of two antioxidant response element sequences in the CYB5R3 promoter led
      to chromatin immunoprecipitation studies, which showed that cellular stressors
      enhanced the binding of Nrf2 and FOXO3a to the CYB5R3 promoter. INNOVATION: Our
      findings demonstrate that CYB5R3 contributes to regulate redox homeostasis,
      aerobic metabolism, and cellular senescence, suggesting that CYB5R3 might be a
      key effector of oxidative and nutritional stress pathways. The expression of
      CYB5R3 is regulated by the cooperation of Nrf2 and FOXO3a. CONCLUSION: CYB5R3 is
      an essential gene that appears as a final effector for both nutritional and
      oxidative stress responses through FOXO3a and Nrf2, respectively, and their
      interaction promotes CYB5R3 expression. These results unveil a potential
      mechanism of action by which CYB5R3 deficiency contributes to the
      pathophysiological underpinnings of neurological disorders in RHM patients.

PMID- 24450885
TI  - Transcriptomic analysis of Streptomyces clavuligerus DeltaccaR::tsr: effects of
      the cephamycin C-clavulanic acid cluster regulator CcaR on global regulation.
AB  - Streptomyces clavuligerus ATCC 27064 and S. clavuligerus DeltaccaR::tsr cultures
      were grown in asparagine-starch medium, and samples were taken in the exponential
      and stationary growth phases. Transcriptomic analysis showed that the expression
      of 186 genes was altered in the ccaR-deleted mutant. These genes belong to the
      cephamycin C gene cluster, clavulanic acid gene cluster, clavams, holomycin,
      differentiation, carbon, nitrogen, amino acids or phosphate metabolism and energy
      production. All the clavulanic acid biosynthesis genes showed Mc values in the
      order of -4.23. The blip gene-encoding a beta-lactamase inhibitory protein was
      also controlled by the cephamycin C-clavulanic acid cluster regulator (Mc -2.54).
      The expression of the cephamycin C biosynthesis genes was greatly reduced in the
      mutant (Mc values up to -7.1), while the genes involved in putative beta-lactam
      resistance were less affected (Mc average -0.88). Genes for holomycin
      biosynthesis were upregulated. In addition, the lack of clavulanic acid and
      cephamycin production negatively affected the expression of genes for the
      clavulanic acid precursor arginine and of miscellaneous genes involved in
      nitrogen metabolism (amtB, glnB, glnA3, glnA2, glnA1). The transcriptomic results
      were validated by quantative reverse transcription polymerase chain reaction and
      luciferase assay of luxAB-coupled promoters. Transcriptomic analysis of the
      homologous genes of S. coelicolor validated the results obtained for S.
      clavuligerus primary metabolism genes.

PMID- 24450887
TI  - Composition dependent Stokes shift dynamics in binary mixtures of 1-butyl-3
      methylimidazolium tetrafluoroborate with water and acetonitrile: quantitative
      comparison between theory and complete measurements.
AB  - Here we predict, using a semimolecular theory, the Stokes shift dynamics of a
      dipolar solute in binary mixtures of an ionic liquid (IL), 1-butyl-3
      methylimidazolium tetrafluoroborate ([Bmim][BF4]), with water (H2O) and
      acetonitrile (CH3CN), and compare with the experimental results. The latter are
      from the recent measurements that combined broad-band fluorescence up-conversion
      (FLUPS) with time-correlated single photon counting (TCSPC) techniques and used
      coumarin 153 (C153) as a solute probe. Nine different compositions of
      ([Bmim][BF4] + H2O) and ([Bmim][BF4] + CH3CN) binary mixtures are considered for
      the extensive comparison between theory and experiments. Two separate model
      calculations have been performed using the available experimental frequency
      dependent dielectric function, epsilon(omega). These calculations
      semiquantitatively reproduce the experimentally observed (i) IL mole fraction
      dependence of dynamic Stokes shifts in these mixtures, (ii) composition
      dependence of average fast, slow, and solvation times, (iii) viscosity dependence
      of slow times, and (iv) the nonlinear dependence of average solvation times on
      experimental inverse conductivity. Variations of the calculated dynamics on water
      dipole moment values (gas phase or liquid phase) and sensitivity to different
      measurements of epsilon(omega) for ([Bmim][BF4] + H2O) mixtures are examined. In
      addition, the importance of the missing contribution to experimental
      epsilon(omega) from high frequency collective solvent intermolecular modes for
      generating the experimentally observed sub-picosecond solvation response in these
      (IL + polar solvent) binary mixtures has been explored. 

PMID- 24450886
TI  - MET dysregulation is a hallmark of aggressive disease in multiple myeloma
      patients.
AB  - Abnormal activation of MET/HGF (Hepatocyte Growth Factor) pathway has been
      described in several tumours and increased HGF plasmatic levels have been
      detected in patients with aggressive multiple myeloma (MM). MET and HGF mRNA
      expression was investigated in 105 samples of purified plasma cells derived from
      newly diagnosed MM patients treated with bortezomib-based induction therapy. Gene
      expression was compared with response to therapy and clinical outcome. MET gene
      copy number was also evaluated. MET mRNA expression was higher in CD138(+) than
      in CD138(-) cells (median 76.90 vs. 11.24; P = 0.0009). Low MET mRNA expression
      characterized patients with better response (complete response or very good
      partial response) compared to other patients (median 56.10 vs. 134.83; P =
      0.0006). After a median follow-up of 50 months, patients with high MET mRNA
      expression displayed a worse progression-free survival (PFS; P = 0.0029) and
      overall survival (OS; P = 0.0023) compared to those with low MET mRNA levels.
      Patients with both high MET mRNA expression and high beta2-microglobulin level
      (>5.5 mg/l) had further worse median PFS (P < 0.0001) and OS (P < 0.0001).
      Patients carrying 4 MET gene copies (8 out of 82, 9.8%) also had a short PFS.
      High MET mRNA expression identifies patients with dismal PFS and OS and the
      combination with high beta2-microglobulin further characterizes patients with
      worse outcome.

PMID- 24450888
TI  - Smoke, the chief killer--strategies for targeting combustible tobacco use.

PMID- 24450889
TI  - A trial of mass isoniazid preventive therapy for tuberculosis control.
AB  - BACKGROUND: Tuberculosis is epidemic among workers in South African gold mines.
      We evaluated an intervention to interrupt tuberculosis transmission by means of
      mass screening that was linked to treatment for active disease or latent
      infection. METHODS: In a cluster-randomized study, we designated 15 clusters with
      78,744 miners as either intervention clusters (40,981 miners in 8 clusters) or
      control clusters (37,763 miners in 7 clusters). In the intervention clusters, all
      miners were offered tuberculosis screening. If active tuberculosis was diagnosed,
      they were referred for treatment; if not, they were offered 9 months of isoniazid
      preventive therapy. The primary outcome was the cluster-level incidence of
      tuberculosis during the 12 months after the intervention ended. Secondary
      outcomes included tuberculosis prevalence at study completion. RESULTS: In the
      intervention clusters, 27,126 miners (66.2%) underwent screening. Of these
      miners, 23,659 (87.2%) started taking isoniazid, and isoniazid was dispensed for
      6 months or more to 35 to 79% of miners, depending on the cluster. The
      intervention did not reduce the incidence of tuberculosis, with rates of 3.02 per
      100 person-years in the intervention clusters and 2.95 per 100 person-years in
      the control clusters (rate ratio in the intervention clusters, 1.00; 95%
      confidence interval [CI], 0.75 to 1.34; P=0.98; adjusted rate ratio, 0.96; 95%
      CI, 0.76 to 1.21; P=0.71), or the prevalence of tuberculosis (2.35% vs. 2.14%;
      adjusted prevalence ratio, 0.98; 95% CI, 0.65 to 1.48; P=0.90). Analysis of the
      direct effect of isoniazid in 10,909 miners showed a reduced incidence of
      tuberculosis during treatment (1.10 cases per 100 person-years among miners
      receiving isoniazid vs. 2.91 cases per 100 person-years among controls; adjusted
      rate ratio, 0.42; 95% CI, 0.20 to 0.88; P=0.03), but there was a subsequent rapid
      loss of protection. CONCLUSIONS: Mass screening and treatment for latent
      tuberculosis had no significant effect on tuberculosis control in South African
      gold mines, despite the successful use of isoniazid in preventing tuberculosis
      during treatment. (Funded by the Consortium to Respond Effectively to the AIDS TB
      Epidemic and others; Thibela TB Current Controlled Trials number,
      ISRCTN63327174.).

PMID- 24450890
TI  - Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease is characterized by amyloid-beta plaques,
      neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized
      monoclonal antibody, preferentially binds soluble forms of amyloid and in
      preclinical studies promoted its clearance from the brain. METHODS: In two phase
      3, double-blind trials (EXPEDITION 1 and EXPEDITION 2), we randomly assigned 1012
      and 1040 patients, respectively, with mild-to-moderate Alzheimer's disease to
      receive placebo or solanezumab (administered intravenously at a dose of 400 mg)
      every 4 weeks for 18 months. The primary outcomes were the changes from baseline
      to week 80 in scores on the 11-item cognitive subscale of the Alzheimer's Disease
      Assessment Scale (ADAS-cog11; range, 0 to 70, with higher scores indicating
      greater cognitive impairment) and the Alzheimer's Disease Cooperative Study
      Activities of Daily Living scale (ADCS-ADL; range, 0 to 78, with lower scores
      indicating worse functioning). After analysis of data from EXPEDITION 1, the
      primary outcome for EXPEDITION 2 was revised to the change in scores on the 14
      item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14;
      range, 0 to 90, with higher scores indicating greater impairment), in patients
      with mild Alzheimer's disease. RESULTS: Neither study showed significant
      improvement in the primary outcomes. The modeled difference between groups
      (solanezumab group minus placebo group) in the change from baseline was -0.8
      points for the ADAS-cog11 score (95% confidence interval [CI], -2.1 to 0.5;
      P=0.24) and -0.4 points for the ADCS-ADL score (95% CI, -2.3 to 1.4; P=0.64) in
      EXPEDITION 1 and -1.3 points (95% CI, -2.5 to 0.3; P=0.06) and 1.6 points (95%
      CI, -0.2 to 3.3; P=0.08), respectively, in EXPEDITION 2. Between-group
      differences in the changes in the ADAS-cog14 score were -1.7 points in patients
      with mild Alzheimer's disease (95% CI, -3.5 to 0.1; P=0.06) and -1.5 in patients
      with moderate Alzheimer's disease (95% CI, -4.1 to 1.1; P=0.26). In the combined
      safety data set, the incidence of amyloid-related imaging abnormalities with
      edema or hemorrhage was 0.9% with solanezumab and 0.4% with placebo for edema
      (P=0.27) and 4.9% and 5.6%, respectively, for hemorrhage (P=0.49). CONCLUSIONS:
      Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to
      improve cognition or functional ability. (Funded by Eli Lilly; EXPEDITION 1 and 2
      ClinicalTrials.gov numbers, NCT00905372 and NCT00904683.).

PMID- 24450894
TI  - Images in clinical medicine. Chorioretinal toxoplasmosis.

PMID- 24450895
TI  - Case records of the Massachusetts General Hospital. Case 3-2014. A 61-year-old
      woman with gastrointestinal symptoms, anemia, and acute kidney injury.

PMID- 24450893
TI  - Acute osteomyelitis in children.

PMID- 24450897
TI  - Antiamyloid therapy for Alzheimer's disease--are we on the right road?

PMID- 24450896
TI  - Troubles with tuberculosis prevention.

PMID- 24450892
TI  - National trends in patient safety for four common conditions, 2005-2011.
AB  - BACKGROUND: Changes in adverse-event rates among Medicare patients with common
      medical conditions and conditions requiring surgery remain largely unknown.
      METHODS: We used Medicare Patient Safety Monitoring System data abstracted from
      medical records on 21 adverse events in patients hospitalized in the United
      States between 2005 and 2011 for acute myocardial infarction, congestive heart
      failure, pneumonia, or conditions requiring surgery. We estimated trends in the
      rate of occurrence of adverse events for which patients were at risk, the
      proportion of patients with one or more adverse events, and the number of adverse
      events per 1000 hospitalizations. RESULTS: The study included 61,523 patients
      hospitalized for acute myocardial infarction (19%), congestive heart failure
      (25%), pneumonia (30%), and conditions requiring surgery (27%). From 2005 through
      2011, among patients with acute myocardial infarction, the rate of occurrence of
      adverse events declined from 5.0% to 3.7% (difference, 1.3 percentage points; 95%
      confidence interval [CI], 0.7 to 1.9), the proportion of patients with one or
      more adverse events declined from 26.0% to 19.4% (difference, 6.6 percentage
      points; 95% CI, 3.3 to 10.2), and the number of adverse events per 1000
      hospitalizations declined from 401.9 to 262.2 (difference, 139.7; 95% CI, 90.6 to
      189.0). Among patients with congestive heart failure, the rate of occurrence of
      adverse events declined from 3.7% to 2.7% (difference, 1.0 percentage points; 95%
      CI, 0.5 to 1.4), the proportion of patients with one or more adverse events
      declined from 17.5% to 14.2% (difference, 3.3 percentage points; 95% CI, 1.0 to
      5.5), and the number of adverse events per 1000 hospitalizations declined from
      235.2 to 166.9 (difference, 68.3; 95% CI, 39.9 to 96.7). Patients with pneumonia
      and those with conditions requiring surgery had no significant declines in
      adverse-event rates. CONCLUSIONS: From 2005 through 2011, adverse-event rates
      declined substantially among patients hospitalized for acute myocardial
      infarction or congestive heart failure but not among those hospitalized for
      pneumonia or conditions requiring surgery. (Funded by the Agency for Healthcare
      Research and Quality and others.).

PMID- 24450898
TI  - Immunotherapy for HIV Infection.

PMID- 24450899
TI  - Dabigatran in patients with mechanical heart valves.

PMID- 24450900
TI  - Dabigatran in patients with mechanical heart valves.

PMID- 24450901
TI  - Dabigatran in patients with mechanical heart valves.

PMID- 24450902
TI  - Dabigatran in patients with mechanical heart valves.

PMID- 24450903
TI  - Dabigatran in patients with mechanical heart valves.

PMID- 24450904
TI  - Dabigatran in patients with mechanical heart valves.

PMID- 24450905
TI  - High-flow nasal cannulae in very preterm infants after extubation.

PMID- 24450906
TI  - High-flow nasal cannulae in very preterm infants after extubation.

PMID- 24450907
TI  - High-flow nasal cannulae in very preterm infants after extubation.

PMID- 24450908
TI  - High-flow nasal cannulae in very preterm infants after extubation.

PMID- 24450909
TI  - High-flow nasal cannulae in very preterm infants after extubation.

PMID- 24450910
TI  - Calcium supplements and fracture prevention.

PMID- 24450911
TI  - Calcium supplements and fracture prevention.

PMID- 24450912
TI  - Calcium supplements and fracture prevention.

PMID- 24450913
TI  - Temporary pelvic stabilization after trauma.

PMID- 24450914
TI  - Temporary pelvic stabilization after trauma.

PMID- 24450915
TI  - An outbreak of exposure to a novel synthetic cannabinoid.

PMID- 24450916
TI  - Images in clinical medicine. Ocular manifestation of electrical burn.

PMID- 24450920
TI  - Ginsenoside metabolite compound K attenuates inflammatory responses of adjuvant
      induced arthritis rats.
AB  - OBJECTIVE: To investigate the effects of ginsenoside metabolite compound K (CK)
      on adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on the
      function of immunocyte (B cell and macrophage) and effectors' cell (fibroblast
      like synoviocyte, FLS). METHODS: Animals were divided randomly into nine groups
      including control, AA, CK (5, 10, 20, 40, 80, and 160 mg/kg, i.g.), and MTX (0.5
      mg/kg, i.g.). The effects of CK on AA rats are evaluated by swelling of the paw,
      histopathology of joint, and inflammatory cytokine production in serum. To
      further investigate the effects of CK on the function of B cell, peritoneal
      macrophage, and FLS from AA rats, we examined the proliferation of B cell and FLS
      by [3H] thymidine incorporation, and the phagocytic function of peritoneal
      macrophage was measured by neutral red uptake. Cytokines and antibodies in serum
      and the supernatant from peritoneal macrophage and FLS were measured by ELISA
      kit. RESULTS: CK suppressed the severity of AA rats by attenuating the paw
      swelling and histopathology of joint. CK can inhibit the proliferation of B cell
      and autoantibody levels, and suppressed the phagocytic function of peritoneal
      macrophage and secreted pro-inflammatory cytokines TNF-alpha, IFN-gamma, and IL
      17 and up-regulated the level of protective cytokines IL-10. CK attenuated the
      proliferation of FLS, and balanced the ratio of RANKL to OPG in AA rats.
      CONCLUSION: Our results suggest that CK may attenuate the severity of AA rats,
      partially by influencing the function of immunocyte (B cell and macrophage) and
      effectors' cells (FLS) in AA.

PMID- 24450922
TI  - Characterization of distinct root and shoot responses to low-oxygen stress in
      Arabidopsis with a focus on primary C- and N-metabolism.
AB  - Oxygen deficiency, caused by flooding of all or a portion of a plant, leads to
      significant gene regulatory and metabolic responses associated with survival.
      When oxygen-deprived in light, aerial organs and root systems respond in distinct
      manners because of their respective autotrophy and heterotrophy, as well as
      intrinsic differences in cell biology and organ function. To better understand
      organ-specific responses to oxygen deficiency, we monitored changes in the
      metabolome of roots and shoots of Arabidopsis thaliana seedlings using gas
      chromatography-mass spectrometry and (1) H-nuclear magnetic resonance
      spectroscopy. Only roots accumulated high amounts of gamma-aminobutyrate (GABA)
      and lactate, whereas both organs accumulated alanine (Ala) upon hypoxia. Meta
      analysis of gene regulation data revealed higher induction of mRNAs coding for
      fermentative enzymes in roots as compared with shoots. However, the elevation in
      GABA level was not correlated with changes in transcript abundance, supporting
      the proposal that post-translational mechanisms are important in metabolic
      acclimation to hypoxia. The biosynthesis, degradation and function of GABA and
      Ala during oxygen deprivation and re-aeration is discussed. Finally, a systematic
      survey of low-oxygen mediated regulation of genes associated with primary
      metabolism across organs and cell types reveals exciting new avenues for future
      studies. 

PMID- 24450925
TI  - Strawberry and human health: effects beyond antioxidant activity.
AB  - The usefulness of a diet rich in vegetables and fruits on human health has been
      widely recognized: a high intake of antioxidant and bioactive compounds may in
      fact play a crucial role in the prevention of several diseases, such as cancer,
      cardiovascular, neurodegenerative, and other chronic pathologies. The strawberry
      (Fragaria * ananassa Duch.) possesses a remarkable nutritional composition in
      terms of micronutrients, such as minerals, vitamin C, and folates, and non
      nutrient elements, such as phenolic compounds, that are essential for human
      health. Although strawberry phenolics are known mainly for their anti
      inflammatory and antioxidant actions, recent studies have demonstrated that their
      biological activities also spread to other pathways involved in cellular
      metabolism and cellular survival. This paper has the main objective of reviewing
      current information about the potential mechanisms involved in the effects
      elicited by strawberry polyphenols on human health, devoting special attention to
      the latest findings. 

PMID- 24450927
TI  - In situ KPFM imaging of local photovoltaic characteristics of structured organic
      photovoltaic devices.
AB  - Here, we discuss the local photovoltaic characteristics of a structured bulk
      heterojunction, organic photovoltaic devices fabricated with a liquid carbazole,
      and a fullerene derivative based on analysis by scanning kelvin probe force
      microscopy (KPFM). Periodic photopolymerization induced by an interference
      pattern from two laser beams formed surface relief gratings (SRG) in the
      structured films. The surface potential distribution in the SRGs indicates the
      formation of donor and acceptor spatial distribution. Under illumination, the
      surface potential reversibly changed because of the generation of fullerene
      anions and hole transport from the films to substrates, which indicates that we
      successfully imaged the local photovoltaic characteristics of the structured
      photovoltaic devices. Using atomic force microscopy, we confirmed the formation
      of the SRG because of the material migration to the photopolymerized region of
      the films, which was induced by light exposure through photomasks. The
      structuring technique allows for the direct fabrication and the control of donor
      and acceptor spatial distribution in organic photonic and electronic devices with
      minimized material consumption. This in situ KPFM technique is indispensable to
      the fabrication of nanoscale electron donor and electron acceptor spatial
      distribution in the devices. 

PMID- 24450926
TI  - Neuropathologic assessment of dementia markers in identical and fraternal twins.
AB  - Twin studies are an incomparable source of investigation to shed light on genetic
      and non-genetic components of neurodegenerative diseases, as Alzheimer's disease
      (AD). Detailed clinicopathologic correlations using twin longitudinal data and
      post-mortem examinations are mostly missing. We describe clinical and pathologic
      findings of seven monozygotic (MZ) and dizygotic (DZ) twin pairs. Our findings
      show good agreement between clinical and pathologic diagnoses in the majority of
      the twin pairs, with greater neuropathologic concordance in MZ than DZ twins.
      Greater neuropathologic concordance was found for beta-amyloid than tau pathology
      within the pairs. ApoE4 was associated with higher beta-amyloid and earlier
      dementia onset, and importantly, higher frequency of other co-occurring brain
      pathologies, regardless of the zygosity. Dementia onset, dementia duration,
      difference between twins in age at dementia onset and at death, did not correlate
      with AD pathology. These clinicopathologic correlations of older identical and
      fraternal twins support the relevance of genetic factors in AD, but not their
      sufficiency to determine the pathology, and consequently the disease, even in
      monozygotic twins. It is the interaction among genetic and non-genetic risks
      which plays a major role in influencing, or probably determining, the
      degeneration of those brain circuits associated with pathology and cognitive
      deficits in AD. 

PMID- 24450929
TI  - Selective alternate derivatization of the hexaphenylbenzene framework through a
      thermodynamically controlled halogen dance.
AB  - We report a practical synthetic protocol and mechanistic details for the
      selective alternate derivatization of the hexaphenylbenzene (HPB) framework
      through a thermodynamically controlled halogen dance. The stability of the
      alternately trilithiated species of HPB is interpreted by the through-space
      interaction at the ipso-carbons of the phenyl groups of the HPB framework. By
      using this approach, C3-symmetric and lower-symmetric HPB derivatives possessing
      two or three kinds of substituents on the periphery have become easily and
      practically available. 

PMID- 24450928
TI  - Bacterial community structure and functional contributions to emergence of health
      or necrotizing enterocolitis in preterm infants.
AB  - BACKGROUND: Preterm infants represent a unique patient population that is born
      functionally immature and must accomplish development under the influence of a
      hospital environment. Neonatal necrotizing enterocolitis (NEC) is an inflammatory
      intestinal disorder affecting preterm infants. The purpose of this study was to
      evaluate the progression of intestinal microbiota community development between
      preterm infants who remained healthy compared to preterm infants who developed
      NEC. RESULTS: Weekly fecal samples from ten preterm infants, five with NEC and
      five matched healthy controls were obtained. Bacterial DNA from individual fecal
      samples was subjected to sequencing of 16S rRNA-based inventories using the 454
      GS-FLX platform. Fecal samples from control infants demonstrated a temporal
      pattern in their microbiota, which converged toward that of a healthy full term
      breast-fed infant. Microbiota development in NEC patients diverged from controls
      beginning three weeks prior to diagnosis. Shotgun metagenomic sequencing was
      performed to identify functional differences in the respective microbiota of
      fecal samples from a set of twins in which one twin developed NEC and one did
      not. The majority of the differentially abundant genes in the NEC patient were
      associated with carbohydrate metabolism and mapped to members of the family
      Enterobacteriaceae. This may indicate an adaptation of the community to an
      altered profile of substrate availability for specific members as a first step
      towards the development of NEC. We propose that the microbial communities as a
      whole may metabolize milk differently, resulting in differential substrate
      availability for specific microbial groups. Additional differentially represented
      gene sets of interest were related to antibiotic resistance and vitamin
      biosynthesis. CONCLUSIONS: Our results suggest that there is a temporal component
      to microbiome development in healthy preterm infants. Thus, bacteriotherapy for
      the treatment or prevention of NEC must consider this temporal component of the
      microbial community in addition to its taxonomic composition and functional
      content.

PMID- 24450931
TI  - Multicentre cluster randomised controlled trial evaluating implementation of a
      fire prevention Injury Prevention Briefing in children's centres: study protocol.
AB  - BACKGROUND: The UK has one of the highest fatality rates for deaths from fire
      related injuries in children aged 0-14 years; these injuries have the steepest
      social gradient of all injuries in the UK. Children's centres provide children
      under five years old and their families with a range of services and information,
      including home safety, but their effectiveness in promoting injury prevention has
      yet to be evaluated. We developed a fire prevention intervention for use in
      children's centres comprising an Injury Prevention Briefing (IPB) which provides
      evidence on what works and best practice from those running injury prevention
      programmes, and a facilitation package to support implementation of the IPB. This
      protocol describes the design and methods of a trial evaluating the effectiveness
      and cost-effectiveness of the IPB and facilitation package in promoting fire
      prevention. METHODS/DESIGN: Pragmatic, multicentre cluster randomised controlled
      trial, with a nested qualitative study, in four study centres in England.
      Children's centres in the most disadvantaged areas will be eligible to
      participate and will be randomised to one of three treatment arms comprising: IPB
      with facilitation package; IPB with no facilitation package; usual care
      (control). The primary outcome measure will be the proportion of families who
      have a fire escape plan at follow-up. Eleven children's centres per arm are
      required to detect an absolute difference in the percentage of families with a
      fire escape plan of 20% in either of the two intervention arms compared with the
      control arm, with 80% power and a 5% significance level (2-sided), an intraclass
      correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families
      per children's centre. Secondary outcomes include the assessment of the cost
      effectiveness of the intervention, other fire safety behaviours and factors
      associated with degree of implementation of the IPB. DISCUSSION: This will be the
      first trial to develop and evaluate a fire prevention intervention for use in
      children's centres in the UK. Its findings will be generalisable to children's
      centres in the most disadvantaged areas of the UK and may also be generalisable
      to similar interventions to prevent other types of injury. TRIAL REGISTRATION:
      http://NCT01452191 (date of registration: 13/10/2011).

PMID- 24450932
TI  - Chabertia erschowi (Nematoda) is a distinct species based on nuclear ribosomal
      DNA sequences and mitochondrial DNA sequences.
AB  - BACKGROUND: Gastrointestinal nematodes of livestock have major socio-economic
      importance worldwide. In small ruminants, Chabertia spp. are responsible for
      economic losses to the livestock industries globally. Although much attention has
      given us insights into epidemiology, diagnosis, treatment and control of this
      parasite, over the years, only one species (C. ovina) has been accepted to infect
      small ruminants, and it is not clear whether C. erschowi is valid as a separate
      species. METHODS: The first and second internal transcribed spacers (ITS-1 and
      ITS-2) regions of nuclear ribosomal DNA (rDNA) and the complete mitochondrial
      (mt) genomes of C. ovina and C. erschowi were amplified and then sequenced.
      Phylogenetic re-construction of 15 Strongylida species (including C. erschowi)
      was carried out using Bayesian inference (BI) based on concatenated amino acid
      sequence datasets. RESULTS: The ITS rDNA sequences of C. ovina China isolates and
      C. erschowi samples were 852-854 bp and 862 -866 bp in length, respectively. The
      mt genome sequence of C. erschowi was 13,705 bp in length, which is 12 bp shorter
      than that of C. ovina China isolate. The sequence difference between the entire
      mt genome of C. ovina China isolate and that of C. erschowi was 15.33%. In
      addition, sequence comparison of the most conserved mt small subunit ribosomal
      (rrnS) and the least conserved nad2 genes among multiple individual nematodes
      revealed substantial nucleotide differences between these two species but limited
      sequence variation within each species. CONCLUSIONS: The mtDNA and rDNA datasets
      provide robust genetic evidence that C. erschowi is a valid strongylid nematode
      species. The mtDNA and rDNA datasets presented in the present study provide
      useful novel markers for further studies of the taxonomy and systematics of the
      Chabertia species from different hosts and geographical regions.

PMID- 24450933
TI  - HIV serostatus disclosure among people living with HIV/AIDS in Mwanza, Tanzania.
AB  - BACKGROUND: Disclosing HIV serostatus is important for HIV prevention and
      maintenance of health for people living with HIV their spouses and the community,
      it plays a role in the social relation which is critical in reducing HIV
      transmission. The process may have positive and negative effects to the HIV
      infected people who disclose their status. The present study was undertaken to
      describe HIV serostatus disclosure among HIV infected people attending care and
      treatment clinic at Sekou-Toure hospital in Mwanza, Tanzania. METHODS: A cross
      sectional study was carried out on 270 HIV infected adults attending Care and
      Treatment Clinic (CTC) at Sekou-Toure hospital between September and October,
      2010. A Swahili questionnaire was used to obtain demographic and HIV disclosure
      information. RESULTS: Hundred and ninety five (72.5%) of all recruited
      participants were females, 88.1% (238/270) were aged above 30 years and 44.1%
      (119/270) were married. The prevalence of serostatus disclosure was 93.3%
      (252/270) with participants aged above 30 years having significantly higher
      proportion of serostatus disclosure compared to those aged below 30 years (94.5%
      vs. 84.4%, p < 0.05). Among the participants who disclosed their status, 69.3%
      reported closeness to the disclosed person as the reason for disclosure while
      25.8% (65/252) disclosed because they needed help. Two hundred (79.4%) reported
      to have received emotional support following disclosure while 25.8% and 29.7%
      received financial support and freedom to use their anti-retroviral drugs around
      the person they disclosed their status respectively. Thirty four participants
      reported to have been discriminated following disclosure and 12 participants
      reported to have been divorced. CONCLUSIONS: Rate of disclosure of HIV serostatus
      was noted to be high in this study. Delayed disclosure was also noted in small
      proportion of participants. Negative outcomes following disclosure of serostatus
      were reported by participants. Efforts need to be increased to promote disclosure
      of HIV serostatus in Tanzania through health education and awareness for both HIV
      infected individuals and the community.

PMID- 24450934
TI  - Isolated growth hormone deficiency (GHD) in childhood and adolescence: recent
      advances.
AB  - The diagnosis of GH deficiency (GHD) in childhood is a multistep process
      involving clinical history, examination with detailed auxology, biochemical
      testing, and pituitary imaging, with an increasing contribution from genetics in
      patients with congenital GHD. Our increasing understanding of the factors
      involved in the development of somatotropes and the dynamic function of the
      somatotrope network may explain, at least in part, the development and
      progression of childhood GHD in different age groups. With respect to the genetic
      etiology of isolated GHD (IGHD), mutations in known genes such as those encoding
      GH (GH1), GHRH receptor (GHRHR), or transcription factors involved in pituitary
      development, are identified in a relatively small percentage of patients
      suggesting the involvement of other, yet unidentified, factors. Genome-wide
      association studies point toward an increasing number of genes involved in the
      control of growth, but their role in the etiology of IGHD remains unknown.
      Despite the many years of research in the area of GHD, there are still
      controversies on the etiology, diagnosis, and management of IGHD in children.
      Recent data suggest that childhood IGHD may have a wider impact on the health and
      neurodevelopment of children, but it is yet unknown to what extent treatment with
      recombinant human GH can reverse this effect. Finally, the safety of recombinant
      human GH is currently the subject of much debate and research, and it is clear
      that long-term controlled studies are needed to clarify the consequences of
      childhood IGHD and the long-term safety of its treatment. 

PMID- 24450935
TI  - Do thyroid ultrasonographic features change according to age in euthyroid dogs?
AB  - The thyroid gland was assessed by ultrasound in healthy euthyroid mixed-breed
      medium size dogs in different age groups. The objective was to verify
      ultrasonographic imaging patterns in these groups, as well as to identify
      possible changes in imaging features resulting from ageing. Thirty dogs - 10
      young (<1 year), 10 adult and 10 elderly - without clinical signs or history of
      thyroid gland disease with complete blood count and thyroid function tests within
      the reference values were evaluated. Each thyroid lobe was examined by ultrasound
      for shape, size, echogenicity and echotexture. The analysis of echogenicity and
      echotexture was made by histogram. Thyroid volume was estimated by the equation
      for ellipsoid (length * width * height) pi/6. The thyroid volume of the young
      dogs in this study had a tendency to be higher than in adult dogs (P = 0.068) and
      older dogs (P = 0.120). The height of the thyroid lobe in the longitudinal plane
      was significantly higher (P = 0.026) in young dogs compared with the other dogs.
      The echotexture and echogenicity had no significant differences between groups,
      but the echogenicity was greater in older dogs. The results point out that
      ultrasound imaging of the thyroid volume is influenced by age in euthyroid dogs.

PMID- 24450937
TI  - Exploring the formation and recognition of an important G-quadruplex in a
      HIF1alpha promoter and its transcriptional inhibition by a benzo[c]phenanthridine
      derivative.
AB  - Four putative G-quadruplex sequences (PGSs) in the HIF1alpha promoter and the
      5'UTR were evaluated for their G-quadruplex-forming potential using ESI-MS, CD,
      FRET, DMS footprinting, and a polymerase stop assay. An important G-quadruplex
      (S1) has been proven to inhibit HIF1alpha transcription by blocking AP2 binding.
      A benzo[c]phenanthridine derivative was found to target the S1 G-quadruplex and
      induce its conformational conversion from antiparallel to parallel orientation.
      The transcriptional suppression of HIF1alpha by this compound was demonstrated
      using western blotting, Q-RT-PCR, luciferase assay, and ChIP. Our new findings
      provided a novel strategy for HIF1alpha regulation and potential insight for
      cancer therapy. 

PMID- 24450936
TI  - Effects of different levels of protein supplementary diet on gene expressions
      related to intramuscular deposition in early-weaned yaks.
AB  - This study was conducted to estimate different levels of protein supplementary
      diet on gene expressions related to intramuscular deposition in early-weaned
      yaks. Results showed that supplementary dietary protein significantly increased
      final weight, average daily gain (ADG), intramuscular fat (IMF), serum free fatty
      acid (FFA), total triglycerides, total cholesterol (Ch), low-density lipoprotein
      cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) content. There
      was a quadratic response of ADG, IMF, FFA, Ch, HDL and LDL to dietary crude
      protein (CP) level. Lipoprotein lipase (LPL), fatty acid synthase (FAS) and
      acetyl-CoA carboxylase (ACC) enzyme activities were significantly increased by
      supplementary dietary CP, while hormone-sensitive lipase (HSL) and carnitine
      palmitoyltransferase-1 (CPT-1) activities were significantly decreased. LPL, ACC
      and FAS enzyme activities showed quadratic increase as dietary CP increased.
      Peroxisome proliferator-activated receptor gamma (PPARgamma), LPL, FAS, sterol
      regulatory element binding protein 1 (SREBP-1), ACC, stearoyl-CoA desaturase
      (SCD) and heart fatty-acid binding protein (H-FABP) gene expression were
      significantly increased by supplementary dietary CP, while HSL and CPT-1 gene
      expression were significantly decreased. PPARgamma, LPL, SREBP-1, ACC and H-FABP
      gene expression showed quadratic increase as dietary CP increased. These results
      indicated that supplementary dietary protein increased IMF accumulation mainly to
      increased intramuscular lipogenic gene expression and decreased lipolytic gene
      expression. 

PMID- 24450938
TI  - Candida albicans aspects of novel silane system-coated titanium and zirconia
      implant surfaces.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effect of novel
      silane system coatings on zirconia and titanium implant surfaces and the
      attachment of the fungal pathogen Candida albicans. MATERIALS AND METHODS:
      Titanium and zirconia specimens were silica-coated and silanized either with a
      commercial silane primer (RelyX Ceramic PrimerTM, 3M ESPE) or a novel silane
      system primer. The novel silane system primer was a blend of 1.0 vol% 3
      acryloxypropyltrimethoxysilane and 0.3 vol% bis-1,2-(triethoxysilyl)ethane
      diluted in acidified ethanol-water solvent. The surface roughness (Ra ), the
      surface free energy and the chemical composition of substrate surfaces after
      treatments were evaluated. C. albcans biofilms were developed on silica-coated +
      silanized surfaces during 48 h of incubation time. Colony forming units (CFU) and
      real-time PCR (RT-PCR) quantified the cells on the material surfaces. Statistical
      analyses were carried out by 1-way ANOVA, Tukey post hoc and Games Howell post
      hoc test at 5% significance level (p). RESULTS: On zirconia and titanium
      surfaces, the Ra and the chemical composition of the specimens were equal (P <
      0.05). The surface free energy was decreased on titanium specimens and increased
      on zirconia specimen after silanization. CFU of C. albicans was significantly
      lower on zirconia coated with RelyX Ceramic PrimerTM, (P < 0.001) and on titanium
      coated with both silanes (P = 0.002). RT-PCR revealed no differences between the
      mean quantities of C. albicans (P >= 0.067). CONCLUSION: Silica-coating and
      silanization had modified the titanium and zirconia surfaces significantly. Both
      the control and experimental silane primers might inhibit the biofilm formation
      of C. albicans.

PMID- 24450939
TI  - Is the reflux disease questionnaire useful for identifying GERD according to the
      Montreal definition?
AB  - BACKGROUND: Scales for aiding physicians diagnose gastro-oesophageal reflux
      disease (GERD) have not been evaluated in terms of their ability to discriminate
      between troublesome symptoms (TS) and non-troublesome symptoms (NTS). Our
      objective is to evaluate the ability of the Reflux Disease Questionnaire (RDQ) to
      identify GERD according to referral of TS, in patients without previous proton
      pump inhibitor (PPI) treatment and in patients on PPI treatment. METHODS:
      Patients consulting physicians because of heartburn or acid regurgitation were
      recruited at 926 primary-care centres in Spain. They were asked to complete
      several questionnaires including the RDQ, and to define which of their symptoms
      were troublesome. Information on drug treatment was collected by the physician.
      We performed a receiver operating characteristic (ROC) curve analysis to
      ascertain the RDQ's optimum cut-point for identifying TS. RESULTS: 4574 patients
      were included, 1887 without PPI and 2596 on PPI treatment. Among those without
      PPI treatment, 1722 reported TS. The area under the curve (AUC) was 0.79 for the
      RDQ, and the optimum RDQ cut-point for identifying TS was 3.18 (sensitivity,
      63.2%; specificity, 80.2%). A total of 2367 patients on PPI treatment reported
      TS, and the optimum RDQ cut-off value was 3.06 (sensitivity, 65.4%; specificity,
      71.8%). CONCLUSIONS: An RDQ score higher than 3 shows good sensitivity and
      specificity for differentiating TS from NTS among patients without PPI or on PPI
      treatment. The RDQ is useful in primary care for diagnosis of GERD based on the
      Montreal definition.

PMID- 24450941
TI  - A combined computational and spectroelectrochemical study of platinum-bridged bis
      triarylamine systems.
AB  - The character of the electronic transitions in the ultraviolet-visible-near
      infrared (UV-vis-NIR) spectra of platinum-bis(alkynyl) bridged, bis-triarylamine
      mixed-valence systems trans-[Pt(C=CC6H4NAr2)2 (PR3)2](n+) (R = ethyl, Ar =
      C6H4CH3-4 (1) or C6H4OCH3-4 (2); R = Ph, Ar = C6H4CH3-4 (3) or C6H4OCH3-4 (4), n
      = 0, 1, 2) has been determined from a combination of spectroscopic measurement
      and density functional theory calculations. The hybrid functional BLYP35 in
      combination with a suitable solvent model (i.e., conductor-like screening model
      (COSMO)) has been used to model the UV-vis-NIR and IR spectroscopic properties of
      [1-4](+), to confirm the description of [1-4](+) as examples of metal-bridged
      organic mixed-valence compounds, and to assign the principal features of the
      electronic spectra, including the triarylamine-based intervalence charge transfer
      transition located in the NIR region. The successful modeling of the charge
      distribution within the system demonstrates the utility of the BLYP35-COSMO
      protocol as a tool for use in the study of intramolecular charge transfer
      properties in mixed-valence complexes. 

PMID- 24450942
TI  - Intraocular pressure, ultrasonographic and echobiometric findings of juvenile
      Yacare caiman (Caiman yacare) eye.
AB  - OBJECTIVE: The aim was to determine the intraocular pressure (IOP), the
      ultrasonographic and echobiometric findings in the eyes of juvenile Yacare caiman
      (Caiman yacare). ANIMALS: Twenty-two healthy caimans from a breeding farm in
      Brazilian Pantanal. PROCEDURES: Intraocular pressure was measured under physical
      restraint and topical anesthesia by applanation tonometry. Five individual
      measurements of each eye were recorded by the same examiner. B-mode
      ultrasonography was performed with a 10-MHz linear transducer, and the anterior
      chamber depth, lens thickness, vitreous depth, and axial globe length were
      measured. Unpaired and paired t-tests were used to assess data. Pearson's test
      was used to assess correlations between IOP and ocular structures (P < 0.05).
      RESULTS: Mean +/- SD IOP of the 44 eyes studied was 9.56 +/- 2.69 mmHg, (range
      5.4-15.6 mmHg). IOP did not differ significantly between right and left eyes or
      between genders (P > 0.05). Echobiometric measurements did not differ
      significantly between eyes and genders (P > 0.05). Intraocular structures
      measured in male and female subjects were, respectively, 2.61 +/- 0.13 and 2.55
      +/- 0.18 mm for anterior chamber depth, 7.60 +/- 0.17 and 7.54 +/- 0.20 mm for
      lens thickness, 6.83 +/- 0.20 and 6.90 +/- 0.22 mm for vitreous chamber depth,
      and 17.55 +/- 0.25 and 17.54 +/- 0.29 mm for axial globe length. Correlations
      were not observed (P > 0.05). CONCLUSION: Reference values of tonometry and
      distances of intraocular structures of Yacare caiman were described. IOP did not
      correlate with echobiometric measurements in this crocodilian. The
      ultrasonographic appearance was similar to other domestic and wild species.

PMID- 24450940
TI  - Oxidant-induced activation of cGMP-dependent protein kinase Ialpha mediates
      neuropathic pain after peripheral nerve injury.
AB  - AIMS: Emerging lines of evidence indicate that oxidants such as hydrogen peroxide
      exert specific signaling functions during the processing of chronic pain.
      However, the mechanisms by which oxidants regulate pain processing in vivo remain
      poorly understood. Here, we investigated whether cyclic guanosine monophosphate
      (cGMP)-dependent protein kinase Ialpha (cGKIalpha), which can be activated by
      oxidants independently of cGMP, serves as a primary redox target during pain
      processing. RESULTS: After peripheral nerve injury, oxidant-induced cGKIalpha
      activation is increased in dorsal root ganglia of mice. Knock-in (KI) mice in
      which cGKIalpha cannot transduce oxidant signals demonstrated reduced neuropathic
      pain behaviors after peripheral nerve injury, and reduced pain behaviors after
      intrathecal delivery of oxidants. In contrast, acute nociceptive, inflammatory,
      and cGMP-induced pain behaviors were not impaired in these mice. INNOVATION:
      Studying cGKIalpha KI mice, we provide the first evidence that oxidants activate
      cGKIalpha in sensory neurons after peripheral nerve injury in vivo. CONCLUSION:
      Our results suggest that oxidant-induced activation of cGKIalpha specifically
      contributes to neuropathic pain processing, and that prevention of cGKIalpha
      redox activation could be a potential novel strategy to manage neuropathic pain.

PMID- 24450943
TI  - Using microwaves to prepare gastropods for DNA barcoding.
AB  - Extracting DNA from gastropods presents particular difficulties due to the
      capacity of the living animal to retract into the shell, resulting in poor
      penetration of the ethanol into the tissues. Because the shell is essential to
      establish the link between sequences and traditional taxonomic identity, cracking
      the shell to facilitate fixation is not ideal. Several methods are currently in
      routine use to overcome this difficulty, including chemical relaxation, drilling
      the shell and boiling. Most of these methods are time-consuming, may be safety
      hazards and constitute a bottleneck in the preparation of large numbers of
      specimens in the field. We have experimented with a method traditionally used to
      clean shells that involves placing the living gastropods in a microwave (MW)
      oven; the electromagnetic radiation very quickly heats both the animal and the
      water trapped inside the shell, resulting in separation of the muscles that
      anchor the animal to the shell. Done properly, the body can be removed intact
      from the shell and the shell voucher is preserved undamaged. To test the method,
      the bodies of live-collected specimens from two gastropod species were separated
      from their shell by microwaving and by anesthetizing/drilling. After identical
      extraction and PCR procedures, the gels showed no difference in DNA quantity or
      quality, and the resulting sequences are identical within species. The method was
      then implemented on a large scale during expeditions, resulting in higher
      percentage of DNA extraction success. The MWs are also effective for quickly and
      easily removing other molluscs from their shells, that is, bivalves and
      scaphopods. Workflows implementing the MW technique show a three- to fivefold
      increase in productivity compared with other methods. 

PMID- 24450945
TI  - Quality of life during chemotherapy and satisfaction with nursing care in Turkish
      breast cancer patients.
AB  - This descriptive cross-sectional study aimed to evaluate quality of life for
      breast cancer patients (n = 105) undergoing chemotherapy, and to assess their
      satisfaction with nursing care. It also explored relationships between quality of
      life, satisfaction with nursing care, and demographic and disease-related
      characteristics. Ethics approval for this study was provided. The research was
      carried out between October 2011 and June 2012. Quality of life and satisfaction
      with nursing care were assessed using the Functional Assessment of Cancer Therapy
      General Scale, the Memorial Symptom Assessment Scale and the Newcastle
      Satisfaction with Nursing Scale. We found that emotional well-being was the area
      most negatively affected, with patients reporting being afraid of death, feeling
      sad and being worried about their health. Patients were overall quite satisfied
      with the nursing care they received at the hospital. We found a positive
      correlation between total scores on the Newcastle Satisfaction with Nursing Scale
      and social and family well-being scores. Breast cancer patients have fears and
      concerns about their health and need support during chemotherapy for coping with
      negative changes in their emotional well-being, physical and functional well
      being. 

PMID- 24450944
TI  - Warfarin untargeted metabolomics study identifies novel procoagulant ethanolamide
      plasma lipids.

PMID- 24450946
TI  - Adsorption of bile salts to milk phospholipid and phospholipid-protein
      monolayers.
AB  - The adsorption of bile salts to milk phospholipid and phospholipid-protein
      monolayers at the air-water interface was studied under simulated intestinal
      conditions using a Langmuir trough, epifluorescence microscopy, and atomic force
      microscopy. Surface pressure changes were affected by temperature, initial
      surface pressure, and bile composition. The rate of addition of bile salts and
      the initial surface pressure of the monolayers had an impact on the
      microstructure of the mixed monolayers. The presence of proteins in monolayers at
      different ratios did not affect the surface pressure change upon addition of
      bile. However, at 20  degrees C, the addition of bile to phospholipid and
      phospholipid-protein monolayers led to different features with branching and
      clustering of liquid-ordered domains and possible formation of bile salt-rich
      areas within liquid-ordered domains. This study provides a basic understanding of
      the interfacial changes occurring at the surface of milk fat globules and milk
      phospholipid liposomes during their passage in the duodenum. 

PMID- 24450947
TI  - Current scenario for the hepatoprotective effects of Inchinkoto, a traditional
      herbal medicine, and its clinical application in liver surgery: A review.
AB  - Inchinkoto (ICKT) is one of the most commonly used herbal medicines as a
      hepatoprotective agent. Among the numerous chemical compounds included in ICKT,
      geniposide is the most abundant component. Geniposide, after p.o. intake, is
      converted to the active metabolite genipin by intestinal bacteria and is absorbed
      in the portal circulation. The biological properties of ICKT and genipin have
      been studied in numerous experiments. Administration of ICKT or genipin exerts
      choleretic effects through upregulation of multidrug resistance-associated
      protein 2 in hepatocytes. ICKT also exerts an anti-apoptotic action through
      inhibition of transforming growth factor-beta1- or tumor necrosis factor-alpha
      dependent signaling pathways. The excessive inflammatory response induced by
      various hepatic stresses is also attenuated by ICKT pre-administration. Moreover,
      ICKT upregulates antioxidant enzymes in the liver under conditions of oxidative
      stress. These experimental results suggest potential benefit of ICKT in liver
      disease and particularly in hepatic surgery, which justify further well-designed
      controlled clinical study. To date, however, clinical data regarding the benefit
      of ICKT for liver surgery are rare. This review article summarized and discussed
      recent evidence relating to the hepatoprotective effects of ICKT in the field of
      basic and clinical science. 

PMID- 24450949
TI  - The PAMPA datasets: a metagenomic survey of microbial communities in Argentinean
      pampean soils.
AB  - BACKGROUND: Soil is among the most diverse and complex environments in the world.
      Soil microorganisms play an essential role in biogeochemical cycles and affect
      plant growth and crop production. However, our knowledge of the relationship
      between species-assemblies and soil ecosystem processes is still very limited.
      The aim of this study was to generate a comprehensive metagenomic survey to
      evaluate the effect of high-input agricultural practices on soil microbial
      communities. RESULTS: We collected soil samples from three different areas in the
      Argentinean Pampean region under three different types of land uses and two soil
      sources (bulk and rhizospheric). We extracted total DNA from all samples and also
      synthetized cDNA from rhizospheric samples. Using 454-FLX technology, we
      generated 112 16S ribosomal DNA and 14 16S ribosomal RNA amplicon libraries
      totaling 1.3 M reads and 36 shotgun metagenome libraries totaling 17.8 million
      reads (7.7 GB). Our preliminary results suggested that water availability could
      be the primary driver that defined microbial assemblages over land use and soil
      source. However, when water was not a limiting resource (annual precipitation
      >800 mm) land use was a primary driver. CONCLUSION: This was the first
      metagenomic study of soil conducted in Argentina and our datasets are among the
      few large soil datasets publicly available. The detailed analysis of these data
      will provide a step forward in our understanding of how soil microbiomes respond
      to high-input agricultural systems, and they will serve as a useful comparison
      with other soil metagenomic studies worldwide.

PMID- 24450950
TI  - Site-selective ion beam synthesis and optical properties of individual CdSe
      nanocrystal quantum dots in a SiO2 matrix.
AB  - Cadmium selenide nanocrystal quantum dots (NC-QDs) are site-selectively
      synthesized by sequential ion beam implantation of selenium and cadmium ions in a
      SiO2 matrix through submicrometer apertures followed by a rapid thermal annealing
      step. The structural and optical properties of the NC-QDs are controlled by the
      ion fluence during implantation and the diameter of the implantation aperture.
      For low fluences and small apertures the emission of these optically active
      emitters is blue-shifted compared to that of the bulk material by >100 meV due to
      quantum confinement. The emission exhibits spectral diffusion and blinking on a
      second time scales as established also for solution-synthesized NC-QDs. 

PMID- 24450951
TI  - Universal vaccination with the quadrivalent HPV vaccine in Austria: impact on
      virus circulation, public health and cost-effectiveness analysis.
AB  - The International Agency for Research on Cancer acknowledges that HPV is a human
      carcinogen affecting both sexes. This study aimed to evaluate the public health
      impact of universal HPV vaccination in Austria, to assess its cost-effectiveness
      and to estimate the HPV prevalence reduction over time. Vaccinating 65% of 9-year
      old boys and girls in Austria would result in a 70% decrease in HPV infections in
      both males and females, hereby avoiding 9500 cases of genital warts annually and
      431 HPV 16/18-related cancers in males and females. This strategy would be cost
      effective with base case analysis of ?26,701/quality-adjusted life year (QALY)
      gained for cervical cancer only, ?15,820/QALY also including vaginal/vulvar
      cancers and genital warts, and ?10,033/QALY also considering anal, oropharyngeal
      and penile cancers, with an incremental cost-effectiveness ratio ranging from
      ?2500 to ?21,000/QALY in sensitivity analyses. HPV circulation would be
      controlled hereby preventing subsequent HPV-related cancers. 

PMID- 24450952
TI  - Suppression of UV-B stress responses by flg22 is regulated at the chromatin level
      via histone modification.
AB  - Genes of the flavonol pathway are activated by UV-B, but suppressed by
      concomitant flg22 application in Arabidopsis. Analysis at the metabolite level
      suggested that this regulation allows the plant to focus its secondary metabolism
      on the plant defence towards pathogen attack. We now demonstrate by chromatin
      immunoprecipitation followed by quantitative PCR, that this antagonistic gene
      regulation is mediated at the chromatin level by differential regulation of
      histone 3 lysine 9 acetylation (H3K9ac), which is a hallmark for gene activation.
      Since H3K9ac levels were altered at least at four independent gene loci, namely,
      chalcone synthase, chalcone-flavone isomerase, flavanone 3-hydroxylase and the
      positive regulator MYB12, which correlates with the observed gene
      activation/suppression reported previously, it appears that this process is
      mediated by chromatin remodelling. Since suppression of H3K9ac prevents gene
      expression, we conclude H3K9ac is rather cause than consequence of gene
      activation. This finding allows us also to extend our working model, involving
      the two opposing MYB transcription factors of the flavonol pathway, MYB12 (being
      UV-B-activated and flg22-suppressed) and MYB4 (a negative regulator, which is
      activated by both flg22 and UV-B stress). 

PMID- 24450953
TI  - Decomposition of L-valine under nonthermal dielectric barrier discharge plasma.
AB  - L-Valine solutions in water and phosphate buffer were treated with nonthermal
      plasma generated by using a dielectric barrier discharge (DBD) device and the
      products generated after plasma treatments were characterized by (1)H NMR and GC
      MS. Our results demonstrate that L-valine is decomposed to acetone, formic acid,
      acetic acid, threo-methylaspartic acid, erythro-methlyaspartic acid, and pyruvic
      acid after direct exposure to DBD plasma. The concentrations of these compounds
      are time-dependent with plasma treatment. The mechanisms of L-valine under the
      DBD plasma are also proposed in this study. Acetone, pyruvic acid, and organic
      radicals (*)CHO, CH3COCH2OO(*) (acetonylperoxy), and CH3COC(OH)2OO(*) (1,1
      dihydroxypropan-2-one peroxy) may be the determining chemicals in DNA damage.

PMID- 24450956
TI  - Vibsatins A and B, two new tetranorvibsane-type diterpenoids from Viburnum tinus
      cv. variegatus.
AB  - Vibsatins A (1) and B (2), a pair of 14,15,16,17-tetranorvibsane-type
      diterpenoids that feature a bicyclo[4.2.1]nonane moiety formed by a new C-13/C-2
      bond, were isolated from the twigs and leaves of Viburnum tinus cv. variegatus.
      The structures and absolute configurations were elucidated by a combination of
      NMR spectra, optical rotation, and X-ray diffraction experiments. A possible
      biogenetic pathway is also proposed. Moreover, vibsatin A (1) enhanced the
      neurite outgrowth of NGF-mediated PC12 cells at a concentration of 10 MUM. 

PMID- 24450958
TI  - Obesity and overweight in Bangladeshi children and adolescents: a scoping review.
AB  - BACKGROUND: Obesity and overweight in children and adolescents is an emerging
      public health concern alongside under-nutrition in low and middle income
      countries. Our aim was to conduct a scoping review of literature to ascertain
      what is known about childhood and adolescent overweight and/or obesity in
      Bangladesh. METHOD: Using the scoping review based on York methodology, a
      comprehensive search of published academic articles, conference proceedings and
      grey literature was carried out through PubMed, BanglaJOL, Google and Google
      scholar limited to English-written papers. We summarized prevalence, risk factors
      and health outcomes of obesity/overweight in young children and adolescents aged
      between 0 to 19 years old in Bangladesh and highlighted use of different
      reference standards to measure childhood obesity. RESULTS: In total 21 studies
      met the inclusion criteria. Nearly all of the reviewed articles used data from
      cross sectional studies, while only two used case-control design. Overall
      thirteen studies (62%) were primary research and eight (38%) included secondary
      data. Studies indicated an increasing trend in childhood obesity over time.
      Prevalence ranged from less than 1% to 17.9% based on different reference
      standards, with higher percentage amongst urban children across different age
      groups and sexes. CONCLUSION: This review demonstrated paucity of comprehensive
      literature on childhood obesity in Bangladesh, which might be explored through
      population-based prospective studies based on strong methodology and uniform
      reference standards. Sustainable and scalable preventative measures targeting
      high risk groups are required to avoid further rise.

PMID- 24450957
TI  - Epidemiology and genetic diversity of Taenia asiatica: a systematic review.
AB  - Taenia asiatica has made a remarkable journey through the scientific literature
      of the past 50 years, starting with the paradoxical observation of high
      prevalences of T. saginata-like tapeworms in non-beef consuming populations, to
      the full description of its mitochondrial genome. Experimental studies conducted
      in the 1980s and 1990s have made it clear that the life cycle of T. asiatica is
      comparable to that of T. saginata, except for pigs being the preferential
      intermediate host and liver the preferential location of the cysts. Whether or
      not T. asiatica can cause human cysticercosis, as is the case for Taenia solium,
      remains unclear. Given the specific conditions needed to complete its life cycle,
      in particular the consumption of raw or poorly cooked pig liver, the transmission
      of T. asiatica shows an important ethno-geographical association. So far, T.
      asiatica has been identified in Taiwan, South Korea, Indonesia, the Philippines,
      Thailand, south-central China, Vietnam, Japan and Nepal. Especially this last
      observation indicates that its distribution is not restricted to South-East-Asia,
      as was thought so far. Indeed, the molecular tools developed over the last 20
      years have made it increasingly possible to differentiate T. asiatica from other
      taeniids. Such tools also indicated that T. asiatica is related more closely to
      T. saginata than to T. solium, feeding the debate on its taxonomic status as a
      separate species versus a subspecies of T. saginata. Furthermore, the genetic
      diversity within T. asiatica appears to be very minimal, indicating that this
      parasite may be on the verge of extinction. However, recent studies have
      identified potential hybrids between T. asiatica and T. saginata, reopening the
      debate on the genetic diversity of T. asiatica and its status as a separate
      species. 

PMID- 24450960
TI  - Morning free and total testosterone in HIV-infected men: implications for the
      assessment of hypogonadism.
AB  - BACKGROUND: Hypogonadism is common among HIV-infected men, even among men
      receiving antiretroviral therapy (ART). Our objective in this study was to
      determine the prevalence of biochemical hypogonadism among HIV-infected men
      compared with HIV-uninfected controls. We also examined the use of free
      testosterone (FT) and total testosterone (TT) measurements in the assessment of
      biochemical hypogonadism in HIV-infected and -uninfected men. METHODS: This was a
      cross-sectional analysis from the Multicenter AIDS Cohort Study (MACS). TT levels
      were measured from archived serum using liquid chromatography-tandem mass
      spectrometry. FT was calculated from TT and sex hormone-binding globulin (SHBG)
      (measured by radioimmunoassay) using the Vermeulen equation. Biochemical
      hypogonadism was defined as having low TT, low FT, or both. RESULTS: Of 945 men
      in the MACS Cardiovascular Substudy, T assays were not performed in 89 because of
      insufficient/no stored serum (n = 18) or use of T replacement therapy (TRT) (n =
      71). 530 men had morning (AM) T measurements; 364 (68.7%) were HIV-infected. The
      prevalence of biochemical hypogonadism was similar in HIV-infected (34/364 =
      9.3%) and HIV-uninfected (12/166 = 7.2%) men. Prevalence of hypogonadism, when
      men on TRT (n = 71) were included in the group of hypogonadal men, was higher in
      HIV-infected (104/434 = 24.0%) compared with HIV-uninfected (13/167 = 7.8%) men
      (p < 0.0001). Of 34 HIV-infected men with biochemical hypogonadism not on TRT, 11
      (32.4%) had normal TT, but low FT. Of 12 HIV-uninfected men with biochemical
      hypogonadism not on TRT, none were in this category (p = 0.04) - all had low TT.
      CONCLUSIONS: The prevalence of biochemical hypogonadism in our sample of HIV
      infected men was approximately 10%, with a substantial proportion of these men
      having a normal TT, but low FT. The measurement of AM FT, rather than TT, in the
      assessment of hypogonadism in HIV-infected men will likely increase diagnostic
      sensitivity and should be recommended.

PMID- 24450959
TI  - Correlation of foodstuffs with ethanol-water mixtures with regard to the
      solubility of migrants from food contact materials.
AB  - Today most foods are available in a packed form. During storage, the migration of
      chemical substances from food packaging materials into food may occur and may
      therefore be a potential source of consumer exposure. To protect the consumer,
      standard migration tests are laid down in Regulation (EU) No. 10/2011. When using
      those migration tests and applying additional conservative conventions, estimated
      exposure is linked with large uncertainties including a certain margin of safety.
      Thus the research project FACET was initiated within the 7th Framework Programme
      of the European Commission with the aim of developing a probabilistic migration
      modelling framework which allows one (1) to calculate migration into foods under
      real conditions of use; and (2) to deliver realistic concentration estimates for
      consumer exposure modelling for complex packaging materials (including multi
      material multilayer structures). The aim was to carry out within the framework of
      the FACET project a comprehensive systematic study on the solubility behaviour of
      foodstuffs for potentially migrating organic chemicals. Therefore a rapid and
      convenient method was established to obtain partition coefficients between
      polymer and food, KP/F. With this method approximately 700 time-dependent kinetic
      experiments from spiked polyethylene films were performed using model migrants,
      foods and ethanol-water mixtures. The partition coefficients of migrants between
      polymer and food (KP/F) were compared with those obtained using ethanol-water
      mixtures (KP/F's) to investigate whether an allocation of food groups with common
      migration behaviour to certain ethanol-water mixtures could be made. These
      studies have confirmed that the solubility of a migrant is mainly dependent on
      the fat content in the food and on the ethanol concentration of ethanol-water
      mixtures. Therefore dissolution properties of generic food groups for migrants
      can be assigned to those of ethanol-water mixtures. All foodstuffs (including dry
      foods) when allocated to FACET model food group codes can be classified into a
      reduced number of food categories each represented by a corresponding ethanol
      water equivalency. 

PMID- 24450961
TI  - Quantitative high content imaging of cellular adaptive stress response pathways
      in toxicity for chemical safety assessment.
AB  - Over the past decade, major leaps forward have been made on the mechanistic
      understanding and identification of adaptive stress response landscapes
      underlying toxic insult using transcriptomics approaches. However, for predictive
      purposes of adverse outcome several major limitations in these approaches exist.
      First, the limited number of samples that can be analyzed reduces the in depth
      analysis of concentration-time course relationships for toxic stress responses.
      Second these transcriptomics analysis have been based on the whole cell
      population, thereby inevitably preventing single cell analysis. Third,
      transcriptomics is based on the transcript level, totally ignoring
      (post)translational regulation. We believe these limitations are circumvented
      with the application of high content analysis of relevant toxicant-induced
      adaptive stress signaling pathways using bacterial artificial chromosome (BAC)
      green fluorescent protein (GFP) reporter cell-based assays. The goal is to
      establish a platform that incorporates all adaptive stress pathways that are
      relevant for toxicity, with a focus on drug-induced liver injury. In addition,
      cellular stress responses typically follow cell perturbations at the subcellular
      organelle level. Therefore, we complement our reporter line panel with reporters
      for specific organelle morphometry and function. Here, we review the approaches
      of high content imaging of cellular adaptive stress responses to chemicals and
      the application in the mechanistic understanding and prediction of chemical
      toxicity at a systems toxicology level.

PMID- 24450962
TI  - Effects of oral administration of heat-killed Enterococcus faecium strain NHRD
      IHARA in post-weaning piglets.
AB  - Probiotic bacteria such as lactic acid bacteria (LAB) have recently received
      attention as candidates for alternative anti-microbial feed additives. We
      previously isolated Enterococcus faecium strain NHRD IHARA (FERM BP-11090, NHRD
      IHARA strain) and reported its probiotic efficacy. However, we have not
      determined the effect of oral administration of heat-killed cells of this strain.
      Here, we performed two experiments to investigate the effect of oral
      administration of the heat-killed NHRD IHARA strain on post-weaning piglets. In
      Experiment 1, there was a significant improvement in growth performance (P =
      0.04) and increase in serum immunoglobulin A (IgA) production (P = 0.03) in the
      group fed heat-killed cells. These results were similar to previous results we
      obtained with live cells. We also found changes in serum and fecal IgA production
      that were unrelated to the patterns of microbiotal change. In Experiment 2, we
      detected a significant improvement in villus growth in the jejunum (P = 0.0002).
      In conclusion, oral administration of the heat-killed NHRD IHARA strain in post
      weaning piglets had the same efficacy as administration of the live strain. The
      heat-killed NHRD IHARA strain can be used as feed additives to improve pig growth
      and health on commercial farms. 

PMID- 24450963
TI  - Xenobiotic effects in the ovary: temporary versus permanent infertility.
AB  - INTRODUCTION: Damage caused by xenobiotic compounds to the ovaries is a subject
      of concern because of their critical role in reproduction. Female mammals are
      born with a finite number of germ cells (oocytes) encased in primordial
      follicles. Xenobiotic-induced damage to primordial follicles can result in early
      ovarian failure (premature menopause). Alternatively, damage affecting larger
      growing follicles can prevent ovulation, thereby causing infertility during
      childbearing years. AREAS COVERED: This review summarizes information from animal
      studies and human observations about xenobiotic compound classes known to target
      the ovary to potentially cause reversible infertility (amenorrhea) as well as
      early ovarian failure. Toxicological evidence supporting ovotoxicity mechanisms
      from some of these compounds is presented. The reader will gain an appreciation
      of how exposures to certain widespread environmental chemicals are of concern as
      regards impacting a woman's reproductive capabilities and life span. EXPERT
      OPINION: Three emerging areas of mechanistic targeting of the ovary by these
      chemicals are identified. These areas relate to the type of cell death, effects
      on follicular development and the importance of ovarian metabolism. In each case,
      the potential translational relevance of these areas to toxicological as well as
      physiological insight is highlighted. A recommendation to expand upon these three
      areas is made.

PMID- 24450964
TI  - Macroscopic anatomy of the lower respiratory system in mole rats (Spalax
      leucodon).
AB  - The morphologic and morphometric features of the lower respiratory system in mole
      rats were examined. It was seen that the low respiratory system of this species
      leading a special life under highly hypoxic/hypercapnic conditions underground is
      structurally similar to other mammals living on land in terms of the parts
      examined; trachea was formed by 29.5 +/- 4 oval-formed cartilaginous tracheals
      arranged backwards and became gradually more stenotic diameter from cranial to
      the caudal of the neck. The trachea was separated in two principal bronchus at
      the fourth thoracal intercostal spatium level. The angle between the two main
      principal bronchi was 60.5 +/- 2.35 degrees . The lung constituted 1.29 +/- 0.03%
      of the body weight and the right lung was heavier than the left lung. Fissura
      inter-lobaris was deep and separated the lung lobes wholly, and the right lung
      was separated in four lobes, whereas the left lung was not separated into the
      lobes. Also, the medial lobe of the left lung was the lightest lobe.

PMID- 24450965
TI  - Do pi-conjugative effects facilitate SN2 reactions?
AB  - Rigorous quantum chemical investigations of the SN2 identity exchange reactions
      of methyl, ethyl, propyl, allyl, benzyl, propargyl, and acetonitrile halides (X =
      F(-), Cl(-)) refute the traditional view that the acceleration of SN2 reactions
      for substrates with a multiple bond at Cbeta (carbon adjacent to the reacting
      Calpha center) is primarily due to pi-conjugation in the SN2 transition state
      (TS). Instead, substrate-nucleophile electrostatic interactions dictate SN2
      reaction rate trends. Regardless of the presence or absence of a Cbeta multiple
      bond in the SN2 reactant in a series of analogues, attractive
      Cbeta(delta(+))...X(delta(-)) interactions in the SN2 TS lower net activation
      barriers (E(b)) and enhance reaction rates, whereas repulsive Cbeta(delta(
      ))...X(delta(-)) interactions increase E(b) barriers and retard SN2 rates. Block
      localized wave function (BLW) computations confirm that pi-conjugation lowers the
      net activation barriers of SN2 allyl (1t, coplanar), benzyl, propargyl, and
      acetonitrile halide identity exchange reactions, but does so to nearly the same
      extent. Therefore, such orbital interactions cannot account for the large range
      of E(b) values in these systems. 

PMID- 24450967
TI  - Intra-epidermal nerve fibres in human skin: back to the roots.
AB  - Regarding the existence and the role of intra-epidermal nerve fibres, the
      literature is ambiguous. However, performing a literature search, a landmark
      paper turned up that even many dermatologists seem to have forgotten, or may not
      even know at all. This paper is entitled 'The innervation of human epidermis'
      written by Arthur and Shelley (J Invest Dermatol, 32, 1959, 397). The full text
      is available via http://www.nature.com/jid/journal/v32/n3/pdf/jid195969a.pdf. The
      authors present data on intra-epidermal nerves at 16 representative body areas.
      The existence of intra-epidermal nerve fibres is undisputable and does not only
      explain clinical symptoms but may even provide a promising target for drug
      development. 

PMID- 24450969
TI  - Trialkylphosphine-stabilized copper(I) dialkylaluminum(III) ethanedithiolate
      complexes: single-source precursors and a novel modification of copper aluminum
      disulfide.
AB  - Four types of trialkylphosphine-stabilized copper dialkylaluminum
      ethanedithiolate complexes with the compositions [(i)Pr3PCuSC2H4SAlR2]2 (R = Me,
      Et, (i)Pr, (t)Bu, vinyl), [((i)Pr3PCu)3(SC2H4S)2AlR2] (R = Et),
      [(Me3P)3CuSC2H4SAlR2] (R = Me, Et), and [(Me3P)4Cu][SC2H4SAlR2] (R = Me, Et,
      (i)Pr) have been synthesized and structurally characterized by X-ray diffraction.
      The first series features an eight-membered (CuSAlS)2 ring as the core structure.
      The trimethylphosphine complexes can be distinguished as nonionic and ionic
      compounds, depending on the amount of trimethylphosphine. In systematic
      thermogravimetric studies, the complexes were converted into the ternary
      semiconductor CuAlS2. In this process, a novel wurtzite-type CuAlS2 phase was
      identified. Binary copper sulfide is observed as a minor side product in
      thermolysis reactions when volatile trialkylaluminum is released. The thermolysis
      reactions are completed at temperatures between 330 and 470  degrees C, depending
      on the aluminum alkyls. The Cu/Al ratio and phase purity of the thermolysis
      products were determined by Rietveld analysis of the powder X-ray diffraction
      patterns and by inductively coupled plasma optical emission spectroscopy
      measurements. To our knowledge, this is the first study of molecular single
      source precursors for CuAlS2. 

PMID- 24450968
TI  - Risk factors for depressed mood amongst a community dwelling older age population
      in England: cross-sectional survey data from the PRO-AGE study.
AB  - BACKGROUND: The Quality and Outcomes Framework in the United Kingdom (UK)
      National Health Service previously highlighted case finding of depression amongst
      patients with diabetes or coronary heart disease. However, depression in older
      people remains under-recognized. Comprehensive data for analyses of the
      association of depression in older age with other health and functional measures,
      and demographic factors from community populations within England, are lacking.
      METHODS: Secondary analyses of cross-sectional baseline survey data from the
      England arm of a randomised controlled trial of health risk appraisal for older
      people in Europe; PRO-AGE study. Data from 1085 community-dwelling non-disabled
      people aged 65 years or more from three group practices in suburban London
      contributed to this study. Depressed mood was ascertained from the 5-item Mental
      Health Inventory Screening test. Exploratory multivariable logistic regression
      was used to identify the strongest associations of depressed mood with a previous
      diagnosis of a specified physical/mental health condition, health and functional
      measures, and demographic factors. RESULTS: Depressed mood occurred in 14%
      (155/1085) of participants. A previous diagnoses of depression (OR 3.39; P <
      0.001) and poor vision as determined from a Visual Function Questionnaire (OR
      2.37; P = 0.001) were amongst the strongest factors associated with depressed
      mood that were independent of functional impairment, other co-morbidities, and
      demographic factors. A subgroup analyses on those without a previous diagnosis of
      depression also indicated that within this group, poor vision (OR 2.51; P =
      0.002) was amongst the strongest independent factors associated with depressed
      mood. CONCLUSIONS: Previous case-finding strategies in primary care focussed on
      heart disease and diabetes but health-related conditions other than coronary
      heart disease and diabetes are also associated with an increased risk for
      depression. Complex issues of multi-morbidity occur within aging populations.
      'Risk' factors that appeared stronger than those, such as, diabetes and coronary
      heart disease that until recently prompted for screening in the UK due to the
      QOF, were identified, and independent of other morbidities associated with
      depressed mood. From the health and functional factors investigated, amongst the
      strongest factors associated with depressed mood was poor vision. Consideration
      to case finding for depressed mood among older people with visual impairment
      might be justified.

PMID- 24450970
TI  - First insights into the transcriptome and development of new genomic tools of a
      widespread circum-Mediterranean tree species, Pinus halepensis Mill.
AB  - Aleppo pine (Pinus halepensis Mill.) is a relevant conifer species for studying
      adaptive responses to drought and fire regimes in the Mediterranean region. In
      this study, we performed Illumina next-generation sequencing of two
      phenotypically divergent Aleppo pine accessions with the aims of (i)
      characterizing the transcriptome through Illumina RNA-Seq on trees phenotypically
      divergent for adaptive traits linked to fire adaptation and drought, (ii)
      performing a functional annotation of the assembled transcriptome, (iii)
      identifying genes with accelerated evolutionary rates, (iv) studying the
      expression levels of the annotated genes and (v) developing gene-based markers
      for population genomic and association genetic studies. The assembled
      transcriptome consisted of 48,629 contigs and covered about 54.6 Mbp. The
      comparison of Aleppo pine transcripts to Picea sitchensis protein-coding
      sequences resulted in the detection of 34,014 SNPs across species, with a Ka /Ks
      average value of 0.216, suggesting that the majority of the assembled genes are
      under negative selection. Several genes were differentially expressed across the
      two pine accessions with contrasted phenotypes, including a glutathione-s
      transferase, a cellulose synthase and a cobra-like protein. A large number of new
      markers (3334 amplifiable SSRs and 28,236 SNPs) have been identified which should
      facilitate future population genomics and association genetics in this species. A
      384-SNP Oligo Pool Assay for genotyping with the Illumina VeraCode technology has
      been designed which showed an high overall SNP conversion rate (76.6%). Our
      results showed that Illumina next-generation sequencing is a valuable technology
      to obtain an extensive overview on whole transcriptomes of nonmodel species with
      large genomes.

PMID- 24450966
TI  - Exercise-induced skeletal muscle remodeling and metabolic adaptation: redox
      signaling and role of autophagy.
AB  - SIGNIFICANCE: Skeletal muscle is a highly plastic tissue. Exercise evokes
      signaling pathways that strongly modify myofiber metabolism and physiological and
      contractile properties of skeletal muscle. Regular physical activity is
      beneficial for health and is highly recommended for the prevention of several
      chronic conditions. In this review, we have focused our attention on the pathways
      that are known to mediate physical training-induced plasticity. RECENT ADVANCES:
      An important role for redox signaling has recently been proposed in exercise
      mediated muscle remodeling and peroxisome proliferator-activated receptor gamma
      (PPARgamma) coactivator-1alpha (PGC-1alpha) activation. Still more currently,
      autophagy has also been found to be involved in metabolic adaptation to exercise.
      CRITICAL ISSUES: Both redox signaling and autophagy are processes with ambivalent
      effects; they can be detrimental and beneficial, depending on their delicate
      balance. As such, understanding their role in the chain of events induced by
      exercise and leading to skeletal muscle remodeling is a very complicated matter.
      Moreover, the study of the signaling induced by exercise is made even more
      difficult by the fact that exercise can be performed with several different
      modalities, with this having different repercussions on adaptation. FUTURE
      DIRECTIONS: Unraveling the complexity of the molecular signaling triggered by
      exercise on skeletal muscle is crucial in order to define the therapeutic
      potentiality of physical training and to identify new pharmacological compounds
      that are able to reproduce some beneficial effects of exercise. In evaluating the
      effect of new "exercise mimetics," it will also be necessary to take into account
      the involvement of reactive oxygen species, reactive nitrogen species, and
      autophagy and their controversial effects.

PMID- 24450971
TI  - State of the art - how I manage coagulopathy in cardiac surgery patients.
AB  - Over 35 000 cardiac operations using cardiopulmonary bypass are performed
      annually in the UK. Post-operative bleeding is a common cause of morbidity.
      Although there have been improvements in surgical techniques, recent publications
      still show post-operative blood loss to be significant, with allogeneic blood
      product usage as high as 50%. Despite greater understanding of the mechanisms of
      the coagulopathy encountered during cardiac surgery the development of treatment
      options has been slow. There has been a realization of the inadequacy of fresh
      frozen plasma to correct the coagulopathy in this setting, leading to greater off
      label use of specific factor concentrates to stop bleeding, e.g., prothrombin
      complex concentrates and fibrinogen concentrates. Recent trials using factor XIII
      and IX concentrates have not been successful. This article will review
      preventative measures to reduce post-operative bleeding and the current
      management of bleeding with such factor concentrates and, in most cases, the
      limited evidence supporting their widespread use.

PMID- 24450972
TI  - Status and challenges for conservation of small mammal assemblages in South
      America.
AB  - South America spans about 44 degrees  latitude, covers almost 18 million km(2) ,
      and is second only to Africa in continental mammal species richness. In spite of
      this richness, research on the status of this fauna and on the nature and
      magnitude of contemporary threats remains limited. Distilling threats to this
      diverse fauna at a continental scale is challenging, in part because of the
      limited availability of rigorous studies. Recognizing this constraint, we
      summarize key threats to small mammals in South America, emphasizing the roles of
      habitat loss and degradation, direct persecution, and the increasing threat of
      climate change. We focus on three regional 'case studies': the tropical Andes,
      Amazonia and adjacent lowland regions, and the southern temperate region. We
      close with a brief summary of recent findings at our long-term research site in
      north-central Chile as they pertain to projected threats to this fauna. Habitat
      alteration is a pervasive threat that has been magnified by market forces and
      globalization (e.g. extensive agricultural development in Amazonia), and
      threatens increasing numbers of populations and species. Climate change poses
      even greater threats, from changes in rainfall and runoff regimes and resulting
      changes in vegetative structure and composition to secondary influences on fire
      dynamics. It is likely that many changes have yet to be recognized, but existing
      threats suggest that the future may bring dramatic changes in the distribution of
      many mammal taxa, although it is not clear if key habitat elements (vegetation)
      will respond as rapidly as climatic factors, leading to substantial uncertainty.
      Climate change is likely to result in 'winners' and 'losers' but available
      information precludes detailed assessment of which species are likely to fall
      into which category. In the absence of long-term monitoring and applied research
      to characterize these threats more accurately, and to develop strategies to
      reduce their impacts, managers already are being faced with daunting challenges.
      As the line between 'pure' and 'applied' research blurs in the face of converging
      interests of scientists and society we hope that solutions to these critical
      issues will be incorporated in addressing anticipated conservation crises. 

PMID- 24450973
TI  - Pathogenesis and management of Wilson disease.
AB  - Hepatolenticular degeneration, commonly known as Wilson disease, is an autosomal
      recessive inherited disease of abnormal copper metabolism, characterized by the
      accumulation of copper in the body due to decreased biliary excretion of copper
      from hepatocytes. Wilson disease protein, ATP7B, functions in copper excretion
      into bile and in copper secretion to the bloodstream coupled with ceruloplasmin
      synthesis. Various kinds of mutations of ATP7B cause Wilson disease. Wilson
      disease is a rare genetic disease that can be treated pharmacologically.
      Recognition and prompt diagnosis are very important, because Wilson disease is
      fatal if left untreated. In this review, I summarize the pathogenesis and
      management of Wilson disease. 

PMID- 24450977
TI  - FENO and AHR mannitol in patients referred to an out-of-hospital asthma clinic: a
      real-life study.
AB  - OBJECTIVE: Ongoing airway inflammation measured by fractional exhaled nitric
      oxide (FENO) and airway hyperresponsiveness (AHR) to mannitol are associated in
      selected asthma patients, but no evidence exists of this association in
      unselected asthma patients. The aim was to investigate the association between
      FENO and AHR to mannitol in unselected individuals with possible asthma. METHODS:
      A real-life study on patients with possible asthma referred to a specialized
      asthma clinic. Data on asthma history, FEV(1), FENO, atopy, smoking, treatment
      and AHR to mannitol were collected. RESULTS: In 217 unselected patients with
      symptoms suggestive of asthma, FENO and response to mannitol were tested. Of the
      141 who underwent both tests, 32 (23%) had FENO > 25 ppb, and 58 (41%) had AHR to
      mannitol. A significant association between high FENO and AHR was found (p <
      0.001); 26% responded to mannitol despite a normal NO, and 8% had a high FENO but
      no AHR. Additionally, a weak association was found between log FENO and log
      response to mannitol (r = 0.32, p < 0.01). The area under the ROC curve for FENO
      as a predictor of AHR was 0.66 (95% CI 0.6-0.8) and for mannitol for having high
      FENO was 0.73 (95%CI 0.6-0.9). CONCLUSION: In a large sample of patients referred
      to an asthma clinic, an association was found between FENO and AHR to mannitol.
      However, a significant proportion of asthma patients had a normal FENO despite
      having AHR, suggesting that in some patients, AHR to mannitol is not driven by
      eosinophilic airway inflammation.

PMID- 24450980
TI  - Ancient hyaenas highlight the old problem of estimating evolutionary rates.
AB  - Phylogenetic analyses of ancient DNA data can provide a timeline for evolutionary
      change even in the absence of fossils. The power to infer the evolutionary rate
      is, however, highly dependent on the number and age of samples, the information
      content of the sequence data and the demographic history of the sampled
      population. In this issue of Molecular Ecology, Sheng et al. (2014) analysed
      mitochondrial DNA sequences isolated from a combination of ancient and present
      day hyaenas, including three Pleistocene samples from China. Using an
      evolutionary rate inferred from the ages of the ancient sequences, they
      recalibrated the timing of hyaena diversification and suggest a much more recent
      evolutionary history than was believed previously. Their results highlight the
      importance of accurately estimating the evolutionary rate when inferring
      timescales of geographical and evolutionary diversification.

PMID- 24450981
TI  - Replicate divergence between and within sounds in a marine fish: the copper
      rockfish (Sebastes caurinus).
AB  - Understanding the factors that influence larval dispersal and connectivity among
      marine populations is critical to the conservation and sustainable management of
      marine resources. We assessed genetic subdivision among ten populations of copper
      rockfish (Sebastes caurinus) representing paired samples of outer coast and the
      heads of inlets in five replicate sounds on the west coast of Vancouver Island,
      British Columbia, using 17 microsatellite DNA loci. Overall, subdivision (F(ST))
      was low (F(ST) = 0.031, P < 0.001), but consistently higher between paired coast
      and head of inlet sites (mean FST = 0.047, P < 0.001) compared to among the five
      coast sites (mean F(ST) = -0.001, P > 0.5) or among the five head of inlet sites
      (mean F(ST) = 0.026, P < 0.001). Heterozygosity, allelic richness and estimates
      of effective population size were also lower in head of inlet sites than in coast
      sites. Bayesian analysis identified two genetic groups across all samples, a
      single genetic group among only coast samples, two genetic groups among head of
      inlet samples and two genetic groups within each sound analysed separately. Head
      of inlet copper rockfish tended to be shorter with lower condition factors and
      grew more slowly than coast sites fish. Reduced physical connectivity and
      selection against immigrants in contrasting outer coast-head of inlet
      environments likely contribute to the evolution of population structure of copper
      rockfish. Based on genetic connectivity, coast sites appear to be better served
      by existing marine protected areas than are head of inlet sites.

PMID- 24450982
TI  - Structure and dynamics of hybrid zones at different stages of speciation in the
      common vole (Microtus arvalis).
AB  - The genetic structure and dynamics of hybrid zones provide crucial information
      for understanding the processes and mechanisms of evolutionary divergence and
      speciation. In general, higher levels of evolutionary divergence between taxa are
      more likely to be associated with reproductive isolation and may result in
      suppressed or strongly restricted hybridization. In this study, we examined two
      secondary contact zones between three deep evolutionary lineages in the common
      vole (Microtus arvalis). Differences in divergence times between the lineages can
      shed light on different stages of reproductive isolation and thus provide
      information on the ongoing speciation process in M. arvalis. We examined more
      than 800 individuals for mitochondrial (mtDNA), Y-chromosome and autosomal
      markers and used assignment and cline analysis methods to characterize the extent
      and direction of gene flow in the contact zones. Introgression of both autosomal
      and mtDNA markers in a relatively broad area of admixture indicates selectively
      neutral hybridization between the least-divergent lineages (Central and Eastern)
      without evidence for partial reproductive isolation. In contrast, a very narrow
      area of hybridization, shifts in marker clines and the quasi-absence of Y
      chromosome introgression support a moving hybrid zone and unidirectional
      selection against male hybrids between the lineages with older divergence
      (Central and Western). Data from a replicate transect further support non-neutral
      processes in this hybrid zone and also suggest a role for landscape history in
      the movement and shaping of geneflow profiles.

PMID- 24450984
TI  - Contemporary generic market in Japan - key conditions to successful evolution.
AB  - The Japanese pharmaceutical market, the world's second largest, is traditionally
      renowned for the domination of patented drugs and the weakest generics share
      among major established economies. An in-depth observation of published evidence
      in Japanese/English language provided closer insight into current trends in
      Japanese domestic legislation and pharmaceutical market development. Recent
      governmental interventions have resulted in significant expansion of the generic
      medicines market size. Substantial savings due to generic substitution of patent
      protected drugs have already been achieved and are likely to increase in future.
      Nationwide population aging threatening sustainable healthcare funding is
      contributing to the relevance of generic policy success. Serious long-term
      challenges to the modest Japanese generic manufacturing capacities will be posed
      by foreign pharmaceutical industries particularly the ones based in emerging BRIC
      economies. 

PMID- 24450983
TI  - Community genomic analyses constrain the distribution of metabolic traits across
      the Chloroflexi phylum and indicate roles in sediment carbon cycling.
AB  - BACKGROUND: Sediments are massive reservoirs of carbon compounds and host a large
      fraction of microbial life. Microorganisms within terrestrial aquifer sediments
      control buried organic carbon turnover, degrade organic contaminants, and impact
      drinking water quality. Recent 16S rRNA gene profiling indicates that members of
      the bacterial phylum Chloroflexi are common in sediment. Only the role of the
      class Dehalococcoidia, which degrade halogenated solvents, is well understood.
      Genomic sampling is available for only six of the approximate 30 Chloroflexi
      classes, so little is known about the phylogenetic distribution of reductive
      dehalogenation or about the broader metabolic characteristics of Chloroflexi in
      sediment. RESULTS: We used metagenomics to directly evaluate the metabolic
      potential and diversity of Chloroflexi in aquifer sediments. We sampled genomic
      sequence from 86 Chloroflexi representing 15 distinct lineages, including members
      of eight classes previously characterized only by 16S rRNA sequences. Unlike in
      the Dehalococcoidia, genes for organohalide respiration are rare within the
      Chloroflexi genomes sampled here. Near-complete genomes were reconstructed for
      three Chloroflexi. One, a member of an unsequenced lineage in the Anaerolinea, is
      an aerobe with the potential for respiring diverse carbon compounds. The others
      represent two genomically unsampled classes sibling to the Dehalococcoidia, and
      are anaerobes likely involved in sugar and plant-derived-compound degradation to
      acetate. Both fix CO2 via the Wood-Ljungdahl pathway, a pathway not previously
      documented in Chloroflexi. The genomes each encode unique traits apparently
      acquired from Archaea, including mechanisms of motility and ATP synthesis.
      CONCLUSIONS: Chloroflexi in the aquifer sediments are abundant and highly
      diverse. Genomic analyses provide new evolutionary boundaries for obligate
      organohalide respiration. We expand the potential roles of Chloroflexi in
      sediment carbon cycling beyond organohalide respiration to include respiration of
      sugars, fermentation, CO2 fixation, and acetogenesis with ATP formation by
      substrate-level phosphorylation.

PMID- 24450985
TI  - New strategy for controlled release of drugs. Potential pinpoint targeting with
      multiresponsive tetraaniline diblock polymer vesicles: site-directed burst
      release with voltage.
AB  - A series of amphiphlic diblock polymers, tetraaniline block with different length
      of poly(N-isopropylacrylamide) (TA-b-PNIPAM), have been successfully synthesized.
      In a suitable solution, the as-synthesized diblock polymers can form stable large
      compound vesicles (LCVs) with multiple bimolecular-layer structure through self
      assembly. These factors, such as the block length, different organic solvent,
      solvent ratio, pH value, temperature, and voltage, which affect the morphology
      and properties of the assembled aggregates, are systematically investigated. When
      the degree of polymerization of PNIPAM block is close to 10, the as-synthesized
      diblock polymer may form stable LCVs with the uniform size as well as few defects
      in the mixed solvent of dimethylformamide/water (v/v = 3:7). The assembled LCVs
      possess the properties of triple-responsive capacity on temperature, pH, and
      voltage. Variation in any of these factors can cause some changes in the
      morphology of LCVs. The drug release properties for doxorubicin (DOX) loaded by
      LCVs affected by temperature, voltage, and different pH values have been
      investigated. It is interesting that the structure of LCVs can be destructed
      completely by applying a voltage at 0.6 V. With such an advantage, the drugs
      loaded by the LCVs could burst release into designated place by using appropriate
      circuit design or instrument, thus achieving maximum efficacy of the loaded drugs
      or other bioactive molecules without any unnecessary chemical substances added.
      This approach allows us to concentrate more on material design aspects only,
      without regard to the complex targeting issue which is the biggest obstacle of
      such materials in practical applications. 

PMID- 24450986
TI  - Effect of ZnO nanoparticle and hexadecyltrimethylammonium bromide on the dynamic
      and equilibrium oil-water interfacial tension.
AB  - The effect of ZnO nanoparticles on the dynamic and equilibrium interfacial
      tension in the presence and absence of cationic surfactant CTAB was investigated.
      The results show that nanoparticles solely have no effect on interfacial tension.
      However, in the presence of CTAB, both particles and surfactants are adsorbed at
      the interface, and by a synergistic effect decrease the interfacial tension more.
      The effect of ZnO nanoparticles on the contact angle and stability of emulsions
      was studied too. The dynamic interfacial tension data were fitted with two
      different models. The results show that the adsorption mechanism of surfactant
      from bulk to interface was controlled by the mixed diffusion-kinetic model. 

PMID- 24450987
TI  - The practical role of serum allergen-specific IgE as potential biomarker for
      predicting responder to allergen immunotherapy.
AB  - Allergic asthma and rhinitis are characterized by IgE-mediated inflammation
      consequent to the exposure to a specific allergen. Therefore, IgE production may
      be considered the hallmark of allergy. Actually, allergen immunotherapy (AIT) is
      the unique causal treatment for respiratory allergy. Indeed, successful AIT can
      induce a physiologic immune tolerance toward the causal allergen. There is
      evidence to show that AIT is safe and effective; its indication has been
      rigorously stated by robust position papers. AIT efficacy assessment is mainly
      based on symptom reduction and drug saving. AIT responder quote may range between
      60 and 90% of AIT prescription. As AIT is expensive and long-lasting, the
      availability of a marker able to predict AIT responder is a crucial relevance.
      This issue has been the topic of several studies. Very recently, it has been
      preliminarly reported that a cut-off of serum specific IgE levels could define
      AIT-responder. However, further rigorous studies will confirm this view.

PMID- 24450988
TI  - Partial versus complete submergence: snorkelling aids root aeration in Rumex
      palustris but not in R. acetosa.
AB  - The root and shoot tissues of flood-tolerant wetland plants are highly porous to
      enable internal gas phase diffusion of O2 during waterlogging or submergence. In
      the case of only partial submergence (snorkelling), the atmosphere can act as
      source of O2 . The aim of this study was to assess the effect of waterlogging,
      partial submergence and complete submergence in the dark as well as in light on
      O2 partial pressure (pO2 ) in roots of Rumex palustris (flood tolerant) and R.
      acetosa (flood intolerant). We used O2 microelectrodes to measure pO2 of
      adventitious roots during manipulations of the water level around the shoot. Root
      pO2 in both species declined significantly upon submergence but remained oxic
      also when shoots were completely submerged in the dark (0.8 and 4.6 kPa in R.
      acetosa and R. palustris, respectively). The snorkelling effect was substantial
      in R. palustris only. Submergence in light had less impact on root pO2 and the
      effect of snorkelling was also minor. Hence, the benefits of light (underwater
      photosynthesis) and air contact (snorkelling) upon growth and survival in
      submerged wetland plants can now be linked to enhanced internal aeration. 

PMID- 24450989
TI  - Iron-catalyzed arylation of heterocycles via directed C-H bond activation.
AB  - The iron-catalyzed arylation of aromatic heterocycles, such as pyridines,
      thiophenes, and furans, has been achieved. The use of an imine directing group
      allowed for the ortho functionalization of these heterocycles with complete
      conversion in 15 min at 0  degrees C. Yields up to 88% were observed in the
      synthesis of 15 heterocyclic biaryls. 

PMID- 24450990
TI  - Multiparametric PET/CT-perfusion does not add significant additional information
      for initial staging in lung cancer compared with standard PET/CT.
AB  - BACKGROUND: The purpose of this study was to assess the relationship of CT
      perfusion (CTP), 18F-FDG-PET/CT and histological parameters, and the possible
      added value of CTP to FDG-PET/CT in the initial staging of lung cancer. METHODS:
      Fifty-four consecutive patients (median age 65 years, 15 females, 39 males) with
      suspected lung cancer were evaluated prospectively by CT-perfusion scan and 18F
      FDG-PET/CT scan. Overall, 46 tumors were identified. CTP parameters blood flow
      (BF), blood volume (BV), and mean transit time (MTT) of the tumor tissue were
      calculated. Intratumoral microvessel density (MVD) was assessed quantitatively.
      Differences in CTP parameters concerning tumor type, location, PET positivity of
      lymph nodes, TNM status, and UICC stage were analyzed. Spearman correlation
      analyses between CTP and 18F-FDG-PET/CT parameters (SUVmax, SUVmean, PETvol, and
      TLG), MVD, tumor size, and tumor stage were performed. RESULTS: The mean BF
      (mL/100 mL min-1), BV (mL/100 mL), and MTT (s) was 35.5, 8.4, and 14.2,
      respectively. The BF and BV were lower in tumors with PET-positive lymph nodes (p
      = 0.02). However, the CTP values were not significantly different among the N
      stages. The CTP values were not different, depending on tumor size and location.
      No significant correlation was found between CTP parameters and MVD. CONCLUSIONS:
      Overall, the CTP information showed only little additional information for the
      initial staging compared with standard FDG-PET/CT. Low perfusion in lung tumors
      might possibly be associated with metabolically active regional lymph nodes.
      Apart from that, both CTP and 18F-FDG-PET/CT parameter sets may reflect different
      pathophysiological mechanisms in lung cancer.

PMID- 24450991
TI  - Association between lymphocyte and monocyte subsets and cognition in children
      with HIV.
AB  - BACKGROUND: This study assesses the relationships between lymphocyte and monocyte
      subsets and intelligence quotient (IQ) scores in antiretroviral therapy (ART)
      naive, HIV-infected Thai children without advanced HIV disease. FINDINGS: Sixty
      seven ART-naive Thai children with CD4 between 15-24% underwent cognitive testing
      by Weschler intelligence scale and had 13 cell subsets performed by flow
      cytometry including naive, memory and activated subsets of CD4+ and CD8+ T cells,
      activated and perivascular monocytes and B cells. Regression modelling with log10
      cell count and cell percentage transformation was performed.Median age (IQR) was
      9 (7-10) years, 33% were male, CDC stages N:A:B were 1:67:31%, median CD4% and
      count (IQR) were 21 (18-24)%, 597 (424-801) cells/mm3 and HIV RNA (IQR) was 4.6
      (4.1-4.9) log10 copies/ml. Most (82%) lived at home, 45% had a biological parent
      as their primary caregiver, and 26 (49%) had low family income. The mean (SD)
      scores were 75 (13) for full scale IQ (FIQ), 73 (12) for verbal IQ (VIQ) and 80
      (14) for performance IQ (PIQ). Adjusted multivariate regression analysis showed
      significant negative associations between B cell counts and FIQ, VIQ and PIQ (p <
      0.01 for all); similar associations were found for B cell percentages (p < 0.05
      for all). CONCLUSIONS: High B cell counts and percentages were strongly
      associated with poorer FIQ, VIQ and PIQ scores. Prospective, long-term assessment
      of cell subsets and determination of relevant B cell subpopulations could help
      further elucidate associations between lymphocyte subsets and neurocognitive
      development.

PMID- 24450993
TI  - Roles of the zona pellucida and functional exposure of the sperm-egg fusion
      factor 'IZUMO' during in vitro fertilization in pigs.
AB  - The zona pellucida (ZP) is considered to play important roles in the prevention
      of polyspermy in mammalian oocytes. However, in pigs we have shown that the
      presence of the ZP accelerates sperm penetration into the ooplasm during in vitro
      fertilization (IVF). In the present study, we investigated the effects of the ZP
      on sperm binding, acrosomal status, and functional exposure of IZUMO, a critical
      factor involved in sperm-egg fusion, during IVF in pigs. We evaluated the numbers
      and acrosomal statuses of sperm binding to the ZP and oolemma, and being present
      in the ZP and perivitelline space (PVS) using ZP-intact and ZP-free oocytes. More
      sperm bound to the ZP than to the oolemma. The average number of sperm present in
      the PVS was 0.44-0.51 per oocyte, and all sperm had lost their acrosomes. The
      proportion of sperm that were immunopositive for anti-IZUMO antibody was
      significantly higher after they were passing or had passed through the ZP.
      Furthermore, addition of anti-IZUMO antibody to the fertilization medium
      significantly inhibited the penetration of sperm into ZP-free oocytes. These
      results suggest that, in pigs, the ZP induces the acrosome reaction, which is
      associated with the functional exposure of IZUMO, resulting in completion of
      fertilization. 

PMID- 24450992
TI  - Behavioral and technological interventions targeting glycemic control in a
      racially/ethnically diverse population: a randomized controlled trial.
AB  - BACKGROUND: Diabetes self-care by patients has been shown to assist in the
      reduction of disease severity and associated medical costs. We compared the
      effectiveness of two different diabetes self-care interventions on glycemic
      control in a racially/ethnically diverse population. We also explored whether
      reductions in glycated hemoglobin (HbA1c) will be more marked in minority
      persons. METHODS: We conducted an open-label randomized controlled trial of 376
      patients with type 2 diabetes aged >=18 years and whose last measured HbA1c was
      >=7.5% (>=58 mmol/mol). Participants were randomized to: 1) a Chronic Disease
      Self-Management Program (CDSMP; n = 101); 2) a diabetes self-care software on a
      personal digital assistant (PDA; n = 81); 3) a combination of interventions
      (CDSMP + PDA; n = 99); or 4) usual care (control; n = 95). Enrollment occurred
      January 2009-June 2011 at seven regional clinics of a university-affiliated multi
      specialty group practice. The primary outcome was change in HbA1c from
      randomization to 12 months. Data were analyzed using a multilevel statistical
      model. RESULTS: Average baseline HbA1c in the CDSMP, PDA, CDSMP + PDA, and
      control arms were 9.4%, 9.3%, 9.2%, and 9.2%, respectively. HbA1c reductions at
      12 months for the groups averaged 1.1%, 0.7%, 1.1%, and 0.7%, respectively and
      did not differ significantly from baseline based on the model (P = .771). Besides
      the participants in the PDA group reporting eating more high-fat foods compared
      to their counterparts (P < .004), no other significant differences were observed
      in participants' diabetes self-care activities. Exploratory sub-analysis did not
      reveal any marked reductions in HbA1c for minority persons but rather modest
      reductions for all racial/ethnic groups. CONCLUSIONS: Although behavioral and
      technological interventions can result in some modest improvements in glycemic
      control, these interventions did not fare significantly better than usual care in
      achieving glycemic control. More research is needed to understand how these
      interventions can be most effective in clinical practice. The reduction in HbA1c
      levels found in our control group that received usual care also suggests that
      good routine care in an integrated healthcare system can lead to better glycemic
      control. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01221090.

PMID- 24450994
TI  - Redox biology and cell-matrix interactions: an auspicious link-up!
AB  - What do oxygen and its radicals have to do with cell adhesion? Several years ago,
      even experts in the research fields of redox biology and cell adhesion likely
      would have answered this question innocuously or evasively. Is there really
      little to talk about? Some of the former hypotheses on redox biology of cell
      adhesion have substantialized in the meantime. This Forum provides insights into
      the interplay between oxygen radical species and the cellular contacts with the
      extracellular matrix, including the subsequent steps, such as cytoskeleton
      rearrangement. Moreover, it describes evidences that the cell-matrix contact
      influences the production of reactive oxygen species (ROS), thereby underlying
      the potential liaison between redox biology and cell adhesion.

PMID- 24450995
TI  - The need for markers and predictors of Rituximab treatment resistance.
AB  - CD20-specific antibodies show remarkable therapeutic efficacy in B-cell
      malignancy and autoimmune diseases, but due to the occurrence of a significant
      treatment resistance, a critical, unmet need for improving B-cell-depleting
      approaches remains. A CD20 transcript variant (D393-CD20) appears to be
      associated with Rituximab treatment resistance in malignant B cells, but is
      lacking in patients with autoimmune dermatoses as shown by Gamonet et al. While
      CD20-specific factors certainly play a major role in the pathogenesis of
      Rituximab treatment resistance, the D393-CD2 transcript may greatly facilitate
      the development of clinical markers for monitoring the therapy in B-cell
      malignancies and (auto)antibody-mediated diseases. Its association with systemic
      autoimmune diseases should be therefore explored in further studies. 

PMID- 24450997
TI  - Highly mesoporous single-crystalline zeolite beta synthesized using a
      nonsurfactant cationic polymer as a dual-function template.
AB  - Mesoporous zeolites are useful solid catalysts for conversion of bulky molecules
      because they offer fast mass transfer along with size and shape selectivity. We
      report here the successful synthesis of mesoporous aluminosilicate zeolite Beta
      from a commercial cationic polymer that acts as a dual-function template to
      generate zeolitic micropores and mesopores simultaneously. This is the first
      demonstration of a single nonsurfactant polymer acting as such a template. Using
      high-resolution electron microscopy and tomography, we discovered that the
      resulting material (Beta-MS) has abundant and highly interconnected mesopores.
      More importantly, we demonstrated using a three-dimensional electron diffraction
      technique that each Beta-MS particle is a single crystal, whereas most previously
      reported mesoporous zeolites are comprised of nanosized zeolitic grains with
      random orientations. The use of nonsurfactant templates is essential to gaining
      single-crystalline mesoporous zeolites. The single-crystalline nature endows Beta
      MS with better hydrothermal stability compared with surfactant-derived mesoporous
      zeolite Beta. Beta-MS also exhibited remarkably higher catalytic activity than
      did conventional zeolite Beta in acid-catalyzed reactions involving large
      molecules. 

PMID- 24450996
TI  - The epidemiological impact of childhood influenza vaccination using live
      attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation
      study.
AB  - BACKGROUND: Routine annual influenza vaccination is primarily recommended for all
      persons aged 60 and above and for people with underlying chronic conditions in
      Germany. Other countries have already adopted additional childhood influenza
      immunisation programmes. The objective of this study is to determine the
      potential epidemiological impact of implementing paediatric influenza vaccination
      using intranasally administered live-attenuated influenza vaccine (LAIV) in
      Germany. METHODS: A deterministic age-structured model is used to simulate the
      population-level impact of different vaccination strategies on the transmission
      dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate
      the effects of adding a LAIV-based immunisation programme targeting children 2 to
      17 years of age to the existing influenza vaccination policy. The data used in
      the model is based on published evidence complemented by expert opinion. RESULTS:
      In our model, additional vaccination of children 2 to 17 years of age with LAIV
      leads to the prevention of 23.9 million influenza infections and nearly 16
      million symptomatic influenza cases within 10 years. This reduction in burden of
      disease is not restricted to children. About one third of all adult cases can
      indirectly be prevented by LAIV immunisation of children. CONCLUSIONS: Our
      results demonstrate that vaccinating children 2-17 years of age is likely
      associated with a significant reduction in the burden of paediatric influenza.
      Furthermore, annual routine childhood vaccination against seasonal influenza is
      expected to decrease the incidence of influenza among adults and older people due
      to indirect effects of herd protection. In summary, our model provides data
      supporting the introduction of a paediatric influenza immunisation programme in
      Germany.

PMID- 24451000
TI  - Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of
      drug interaction.
AB  - INTRODUCTION: Due to their multiple effects, glucocorticoids (GCs) have versatile
      medical uses. They can regulate many xenobiotic-metabolizing enzymes of the
      cytochrome P450 (CYP) superfamily, and thus, influence pharmacotherapy. AREAS
      COVERED: The aim of this paper is to summarize the molecular effects of GCs on
      CYP as well as the available clinical evidence on drug-drug interactions (DDIs)
      between GCs and other drugs in which GCs influence the metabolism of other
      medicines through modifying CYP activity. We used the factographic database
      DRUGDEX(r) along with bibliographic searches. EXPERT OPINION: Most of the
      literature reported CYP3A4 induction by GCs, but this was not proved in all
      research. As the conclusions on these DDIs are conflicting, there are several
      issues to be considered like the dosage of GCs, the length of GCs treatment and
      concomitant therapy, all of which can have an additive inducing effect. Further,
      in designing a DDI study, crossover studies are preferred. A literature search of
      the abovementioned information resources provided dissimilar results.

PMID- 24450998
TI  - Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory
      bowel diseases.
AB  - Inflammatory bowel diseases are characterized by a deregulated immune response
      targeting the gut bacterial flora. Mucosal-associated invariant T (MAIT) cells
      are major histocompatibility complex (MHC) class Ib-restricted innate-like
      lymphocytes with anti-bacterial functions. They display an effector/memory
      phenotype and are found in large numbers in the blood, mucosae and liver. They
      have also been implicated in inflammatory diseases such as multiple sclerosis.
      Therefore, we aimed to analyse the possible involvement of MAIT cells in Crohn's
      disease (CD) and ulcerative colitis (UC). To this end, a phenotypical and
      functional analysis of MAIT cells isolated from the blood of healthy subjects, CD
      and UC patients was undertaken. MAIT cells were also quantified in ileal biopsies
      of CD patients. The frequency of blood MAIT cells was specifically reduced in IBD
      patients compared with healthy donors, whereas it was dramatically greater in the
      inflamed versus healthy tissue. MAIT cells were activated as they expressed
      significantly more the Ki67 antigen, and this was accompanied by phenotypical
      changes such as increased expression of natural killer (NK)G2D and B and T
      lymphocyte attenuator (BTLA). Finally, in-vitro-activated MAIT cells from CD and
      UC patients secreted significantly more interleukin (IL)-17, together with a
      decreased interferon (IFN)-gamma in CD but an increased IL-22 in UC. These data
      show that MAIT cells are activated in IBD, which results in an increased
      recruitment towards the inflamed tissues, an altered phenotype and a switch in
      the pattern of cytokine secretion. This is the first demonstration that MAIT
      cells are immune players in IBD, whose precise functions in this context need to
      be addressed. 

PMID- 24451001
TI  - Exhaled nitric oxide after high-intensity exercise at 2800 m altitude.
AB  - BACKGROUND: Nitric oxide (NO) concentration in exhaled gas is a marker of some
      inflammatory processes in the lung, and endogenous NO plays a role in the
      physiological responses to exercise and altitude. The aim of this study was to
      compare changes in exhaled NO concentration 5-60 mins after high-intensity
      exercise at 2800 m and at 180 m altitude. METHODS: Twenty trained healthy
      volunteers (12 men), aged 19-28 years, were included in this open, crossover
      study. Subjects performed two exercise tests at different altitudes, 2800 m and
      180 m, in a randomized order. The fraction of NO in exhaled gas (FE(NO)) was
      measured 5 mins before and 5-60 mins after 8 mins of running on a treadmill at a
      heart rate (HR) of 90% of peak HR. Peak HR was assessed during a pretest at 180
      m. Ambient temperature was 20.1 degrees C (SD = 1.2) and relative humidity 40.2%
      (SD = 3.2). FE(NO) measurements were corrected for altitude gas density effects
      and converted to partial pressure of NO (PE(NOcorr)). RESULTS: PE(NOcorr) was
      reduced from 1.47 (1.21, 1.73) millipascal (mPa) at baseline to 1.11 (0.87, 1.34)
      mPa 5 mins after exercise at 2800 m and from 1.54 (1.24, 1.84) to 1.04 (0.87,
      1.22) mPa 5 mins after exercise at 180 m. There was no difference in PE(NOcorr)
      between exercise at 2800 m and 180 m, and PE(NOcorr) was normalized within 20
      mins. CONCLUSIONS: Exercise at 2800 m induces a similar acute reduction in
      exhaled nitric oxide concentration as compared with 180 m in healthy subjects.

PMID- 24451002
TI  - Will booster doses be required for serogroup B meningococcal vaccine?
AB  - The European licensure of 4CMenB, the first vaccine licensed to prevent non
      epidemic meningococcal B (MenB) disease, marked an important milestone in the
      fight against meningococcal disease. However, the potential introduction of
      4CMenB into the routine infant schedule is complicated by a number of factors.
      The recent decline in the number of cases of invasive MenB disease in the UK has
      important implications for cost effectiveness, though the unpredictable nature of
      meningococcal disease epidemiology (as evidenced by a recent outbreak in MenB
      disease at Princeton University) means that it is not clear whether this decline
      will be sustained. The variable waning of antibody levels against each of the
      four key vaccine components also complicates the assessment of the likely
      duration and breadth of protection. After considering these factors, the UK Joint
      Committee on Vaccination and Immunisation (JCVI) released an interim statement in
      July 2013 indicating that the introduction of 4CMenB to the routine infant
      schedule was unlikely to be cost effective but highlighted the need for further
      data on strain coverage and persistence of immunity. This brief editorial
      discusses the possible role that booster doses of 4CMenB may have in prolonging
      persistence of immunity. 

PMID- 24451003
TI  - Effects of vitamin D3 stimulation of thioredoxin-interacting protein in
      hepatocellular carcinoma.
AB  - AIM: Thioredoxin-interacting protein (TXNIP) promotes oxidative stress by
      inactivating thioredoxin (TXN). This protein is involved in diverse disease
      processes, including insulin resistance, atherosclerosis and carcinogenesis. The
      aim of the present study was to measure the expression and function of TXNIP in
      in vitro models of liver disease, as well as in primary human hepatocellular
      carcinoma (HCC) tissue specimens. In addition, we wanted to determine the effects
      of vitamin D3-induced TXNIP stimulation in HCC-derived cell lines. METHODS: TXNIP
      expression was measured by quantitative reverse transcription polymerase chain
      reaction and western blots. TXNIP expression was stimulated by vitamin D exposure
      and by transfection. Cell proliferation, apoptosis and reactive oxygen species
      were determined by standard assays. RESULTS: TXNIP expression levels were low in
      HCC cell lines, and vitamin D3 stimulated TXNIP expression in vitro. In HCC cells
      transfected with a TXNIP expression vector or treated with exogenous vitamin D3,
      there was a reduction in cell proliferation and an increase in apoptosis. Cells
      expressing TXNIP were markedly susceptible to oxidative injury induced by cobalt
      chloride or bacterial lipopolysaccharide. TXNIP expression was reduced or absent
      in a majority of primary human HCC specimens relative to matching, non-cancerous
      liver tissue. CONCLUSION: TXNIP expression is low or absent in human HCC
      specimens and HCC-derived cell lines. Vitamin D3 stimulates TXNIP expression,
      resulting in diminished proliferation and enhanced apoptosis. Liver cells
      expressing TXNIP are primed for oxidative injury. These findings suggest that
      stimulation of TXNIP expression, by factors such as vitamin D3, may attenuate
      carcinogenesis in patients with chronic liver disease.

PMID- 24451005
TI  - "About Brugada phenocopy": Brugada phenocopy with a flecainide overdose: a
      pharmacological dose effect?

PMID- 24451004
TI  - Partitioning of amino acids into a model membrane: capturing the interface.
AB  - Energetics of protein side chain partitioning between aqueous solution and
      cellular membranes is of fundamental importance for correctly capturing the
      membrane binding and specific protein-lipid interactions of peripheral membrane
      proteins. We recently reported a highly mobile membrane mimetic (HMMM) model that
      accelerates lipid dynamics by modeling the membrane interior partially as a fluid
      organic solvent while retaining a literal description of the lipid head groups
      and the beginning of the tails. While the HMMM has been successfully applied to
      study spontaneous insertion of a number of peripheral proteins into membranes, a
      quantitative characterization of the energetics of membrane-protein interactions
      in HMMM membranes has not been performed. We report here the free energy profiles
      for partitioning of 10 protein side chain analogues into a HMMM membrane. In the
      interfacial and headgroup regions of the membrane, the side chain free energy
      profiles show excellent agreement with profiles previously reported for
      conventional membranes with full-tail lipids. In regions where the organic
      solvent is prevalent, the increased dipole and fluidity of the solvent generally
      result in a less accurate description, most notably overstabilization of aromatic
      and polar amino acids. As an additional measure of the ability of the HMMM model
      to describe membrane-protein interactions, the water-to-membrane interface
      transfer energies were analyzed and found to be in agreement with the previously
      reported experimental and computational hydrophobicity scales. We discuss
      strengths and weaknesses of HMMM in describing protein-membrane interactions as
      well as further development of model membranes. 

PMID- 24451006
TI  - Predicting progression to lymphoma in Sjogren's syndrome patients.
AB  - Although the inherent complexity of the multifactorial nature of primary
      Sjogren's syndrome (pSS) renders the process of disease prognostication and
      prediction ambiguous, certain clinical and immunological characteristics have
      been described as lymphoma predictors in several studies. While the association
      between pSS and mucosa-associated lymphoid tissue lymphomas is indisputable,
      recent studies report a predominance of diffuse large B-cell lymphomas implying
      that pSS-lymphoma association is less subtype-specific than previously
      considered. The considerable differences in both disease severity and prognosis
      between patients with various types of lymphoma demand the identification of risk
      factors that can predict the development of the distinct subtypes. Additionally,
      a recently discovered diverse range of biological variables appears to influence
      clinical behavior and lymphoma outcome. In this review, we venture into the area
      of lymphoma prognostication in pSS, outlining long-established predictors,
      analyzing currently available prognostic models, and exploring the predictive
      potential of recent biological and molecular advances. 

PMID- 24451007
TI  - Catalytic reductive dehydration of tertiary amides to enamines under
      hydrosilylation conditions.
AB  - Tertiary amides are efficiently reduced to their corresponding enamines under
      hydrosilylation conditions, using a transition-metal-free catalytic protocol
      based on t-BuOK (5 mol %) and (MeO)3SiH or (EtO)3SiH as the reducing agent. The
      enamines were formed with high selectivity in good-to-excellent yields. 

PMID- 24451008
TI  - ZINClick: a database of 16 million novel, patentable, and readily synthesizable
      1,4-disubstituted triazoles.
AB  - Since Professors Sharpless, Finn, and Kolb first introduced the concept of "click
      reactions" in 2001 as powerful tools in drug discovery, 1,4-disubstituted-1,2,3
      triazoles have become important in medicinal chemistry due to the simultaneous
      discovery by Sharpless, Fokin, and Meldal of a perfect click 1,3-dipolar
      cycloaddition reaction between azides and alkynes catalyzed by copper salts.
      Because of their chemical features, these triazoles are proposed to be aggressive
      pharmacophores that participate in drug-receptor interactions while maintaining
      an excellent chemical and metabolic profile. Surprisingly, no virtual libraries
      of 1,4-disubstituted-1,2,3-triazoles have been generated for the systematic
      investigation of the click-chemical space. In this manuscript, a database of
      triazoles called ZINClick is generated from literature-reported alkynes and
      azides that can be synthesized within three steps from commercially available
      products. This combinatorial database contains over 16 million 1,4-disubstituted
      1,2,3-triazoles that are easily synthesizable, new, and patentable! The
      structural diversity of ZINClick ( http://www.symech.it/ZINClick ) will be
      explored. ZINClick will also be compared to other available databases, and its
      application during the design of novel bioactive molecules containing triazole
      nuclei will be discussed. 

PMID- 24451009
TI  - Comparison of PET template-based and MRI-based image processing in the
      quantitative analysis of C11-raclopride PET.
AB  - BACKGROUND: Quantitative measures of 11C-raclopride receptor binding can be used
      as a correlate of postsynaptic D2 receptor density in the striatum, allowing 11C
      raclopride positron emission tomography (PET) to be used for the differentiation
      of Parkinson's disease from atypical parkinsonian syndromes. Comparison with
      reference values is recommended to establish a reliable diagnosis. A PET template
      specific to raclopride may facilitate direct computation of parametric maps
      without the need for an additional MR scan, aiding automated image analysis.
      METHODS: Sixteen healthy volunteers underwent a dynamic 11C-raclopride PET and a
      high-resolution T1-weighted MR scan of the brain. PET data from eight healthy
      subjects was processed to generate a raclopride-specific PET template normalized
      to standard space. Subsequently, the data processing based on the PET template
      was validated against the standard magnetic resonance imaging (MRI)-based method
      in 8 healthy subjects and 20 patients with suspected parkinsonian syndrome. Semi
      quantitative image analysis was performed in Montreal Neurological Institute
      (MNI) and in original image space (OIS) using VOIs derived from a probabilistic
      brain atlas previously validated by Hammers et al. (Hum Brain Mapp, 15:165-174,
      2002). RESULTS: The striatal-to-cerebellar ratio (SCR) of 11C-raclopride uptake
      obtained using the PET template was in good agreement with the MRI-based image
      processing method, yielding a Lin's concordance coefficient of 0.87. Bland-Altman
      analysis showed that all measurements were within the +/-1.96 standard deviation
      range. In all 20 patients, the PET template-based processing was successful and
      manual volume of interest optimization had no further impact on the diagnosis of
      PD in this patient group. A maximal difference of <5% was found between the
      measured SCR in MNI space and OIS. CONCLUSIONS: The PET template-based method for
      automated quantification of postsynaptic D2 receptor density is simple to
      implement and facilitates rapid, robust and reliable image analysis. There was no
      significant difference between the SCR values obtained with either PET- or MRI
      based image processing. The method presented alleviates the clinical workflow and
      facilitates automated image analysis.

PMID- 24451010
TI  - Chronic Trypanosoma congolense infections in mice cause a sustained disruption of
      the B-cell homeostasis in the bone marrow and spleen.
AB  - Trypanosoma congolense is one of the main species responsible for Animal African
      Trypanosomosis (AAT). As preventive vaccination strategies for AAT have been
      unsuccessful so far, investigating the mechanisms underlying vaccine failure has
      to be prioritized. In T. brucei and T. vivax infections, recent studies revealed
      a rapid onset of destruction of the host B-cell compartment, resulting in the
      loss of memory recall capacity. To assess such effect in experimental T.
      congolense trypanosomosis, we performed infections with both the cloned Tc13
      parasite, which is considered as a standard model system for T. congolense rodent
      infections and the noncloned TRT55 field isolate. These infections differ in
      their virulence level in the C57BL/6 mouse model for trypanosomosis. We show that
      early on, an irreversible depletion of all developmental B cells stages occur.
      Subsequently, in the spleen, a detrimental decrease in immature B cells is
      followed by a significant and permanent depletion of Marginal zone B cells and
      Follicular B cells. The severity of these events later on in infection correlated
      with the virulence level of the parasite stock. In line with this, it was
      observed that later-stage infection-induced IgGs were largely nonspecific, in
      particular in the more virulent TRT55 infection model. 

PMID- 24451011
TI  - Clean method for the synthesis of reduced graphene oxide-supported PtPd alloys
      with high electrocatalytic activity for ethanol oxidation in alkaline medium.
AB  - In this article, a clean method for the synthesis of PtPd/reduced graphene oxide
      (RGO) catalysts with different Pt/Pd ratios is reported in which no additional
      components such as external energy (e.g., high temperature or high pressure),
      surfactants, or stabilizing agents are required. The obtained catalysts were
      characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM),
      high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, X
      ray photoelectron spectroscopy (XPS), induced coupled plasma atomic emission
      spectroscopy (ICP-AES), and electrochemical measurements. The HRTEM measurements
      showed that all of the metallic nanoparticles (NPs) exhibited well-defined
      crystalline structures. The composition of these Pt-Pd/RGO catalysts can be
      easily controlled by adjusting the molar ratio of the Pt and Pd precursors. Both
      cyclic voltammetry (CV) and chronoamperometry (CA) results demonstrate that
      bimetallic PtPd catalysts have superior catalytic activity for the ethanol
      oxidation reaction compared to the monometallic Pt or Pd catalyst, with the best
      performance found with the PtPd (1:3)/RGO catalyst. The present study may open a
      new approach for the synthesis of PtPd alloy catalysts, which is expected to have
      promising applications in fuel cells. 

PMID- 24451012
TI  - mPUMA: a computational approach to microbiota analysis by de novo assembly of
      operational taxonomic units based on protein-coding barcode sequences.
AB  - BACKGROUND: Formation of operational taxonomic units (OTU) is a common approach
      to data aggregation in microbial ecology studies based on amplification and
      sequencing of individual gene targets. The de novo assembly of OTU sequences has
      been recently demonstrated as an alternative to widely used clustering methods,
      providing robust information from experimental data alone, without any reliance
      on an external reference database. RESULTS: Here we introduce mPUMA (microbial
      Profiling Using Metagenomic Assembly, http://mpuma.sourceforge.net), a software
      package for identification and analysis of protein-coding barcode sequence data.
      It was developed originally for Cpn60 universal target sequences (also known as
      GroEL or Hsp60). Using an unattended process that is independent of external
      reference sequences, mPUMA forms OTUs by DNA sequence assembly and is capable of
      tracking OTU abundance. mPUMA processes microbial profiles both in terms of the
      direct DNA sequence as well as in the translated amino acid sequence for protein
      coding barcodes. By forming OTUs and calculating abundance through an assembly
      approach, mPUMA is capable of generating inputs for several popular microbiota
      analysis tools. Using SFF data from sequencing of a synthetic community of Cpn60
      sequences derived from the human vaginal microbiome, we demonstrate that mPUMA
      can faithfully reconstruct all expected OTU sequences and produce compositional
      profiles consistent with actual community structure. CONCLUSIONS: mPUMA enables
      analysis of microbial communities while empowering the discovery of novel
      organisms through OTU assembly.

PMID- 24451013
TI  - Logic control of enzyme-like gold nanoparticles for selective detection of lead
      and mercury ions.
AB  - Functional logic gates based on lead ions (Pb(2+)) and mercury ions (Hg(2+)) that
      induce peroxidase-like activities in gold nanoparticles (Au NPs) in the presence
      of platinum (Pt(4+)) and bismuth ions (Bi(3+)) are presented. The "AND" logic
      gate is constructed using Pt(4+)/Pb(2+) as the input and the peroxidase-like
      activity of the Au NPs as the output; this logic gate is denoted as
      "Pt(4+)/Pb(2+)(AND)-Au NPPOX". When Pt(4+) and Pb(2+) coexist, strong
      metallophilic interactions (between Pt and Pb atoms/ions) and aurophilic
      interactions (between Au and Pb/Pt atoms/ions) result in significant increases in
      the deposition of Pt and Pb atoms/ions onto the Au NPs, leading to enhanced
      peroxidase-like activity. The "INHIBIT" logic gate is fabricated by using Bi(3+)
      and Hg(2+) as the input and the peroxidase-like activity of the Au NPs as the
      output; this logic gate is denoted as "Bi(3+)/Hg(2+)(INHIBIT)-Au NPPOX". High
      peroxidase-like activity of Au NPs in the presence of Bi(3+) is a result of the
      various valence (oxidation) states of Bi(3+) and Au (Au(+)/Au(0)) atoms on the
      nanoparticle's surface. When Bi(3+) and Hg(2+) coexist, strong Hg-Au amalgamation
      results in a large decrease in the peroxidase-like activity of the Au NPs. These
      two probes (Pt(4+)/Pb(2+)(AND)-Au NPPOX and Bi(3+)/Hg(2+)(INHIBIT)-Au NPPOX)
      allow selective detection of Pb(2+) and Hg(2+) down to nanomolar quantities. The
      practicality of these two probes has been validated by analysis of Pb(2+) and
      Hg(2+) in environmental water samples (tap water, river water, and lake water).
      In addition, an integrated logic circuit based on the color change (formation of
      reddish resorufin product) and generation of O2 bubbles from these two probes has
      been constructed, allowing visual detection of Pb(2+) and Hg(2+) in aqueous
      solution. 

PMID- 24451016
TI  - Reproducibility of cardiac biomarkers response to prolonged treadmill exercise.
AB  - We examined the reproducibility of alterations in cardiac biomarkers after two
      identical bouts of prolonged exercise in young athletes. Serum high-sensitivity
      cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT
      proBNP) levels were assessed before and after exercise. Significant rises in
      median hs-cTnT and NT-proBNP occurred in both trials. While the absolute changes
      in hs-cTnT were smaller after trial 2, the pattern of change was similar and the
      delta scores were significantly related. However, the change in NT-proBNP was not
      correlated between trials. The hs-cTnT release demonstrates some consistency
      after exercise although the blunted hc-cTnT response requires further study.

PMID- 24451017
TI  - Female genital mutilation and intimate partner violence in the Ivory Coast.
AB  - BACKGROUND: Serious forms of violence against women include Female Genital
      Mutilation (FGM) and Intimate Partner Violence (IPV). The aim of this study was
      to determine if FGM is associated with IPV, using data obtained from the
      Demographic and Health Survey (DHS) 2012 in Ivory Coast. METHODS: Participants
      for this study were drawn from the 2011-12 Ivory Coast Demographic and Health
      Survey (CDHS), a nationally representative sample of 10060 women aged 15 to 49
      years. The analysis of this paper is restricted to the sample of women who
      responded to the FGM and domestic violence modules (N = 5005). RESULTS: The
      lifetime prevalence of physical violence was 24.8%, sexual violence, 5.7%, and
      emotional violence, 19.0%, and the prevalence of any lifetime IPV was 32.1%. In
      all, 40.6% reported female genital cutting or mutilation (FGM). Women reporting
      FGM were two times as likely to experience sexual IPV (AOR: 1.96, CI: 1.29-2.98),
      while other subtypes of IPV were higher in women reporting FGM but they were not
      significant. Of the socio-demographic covariates, urban residence and having a
      primary education were associated with most subtypes of IPV, while being a Muslim
      seemed protective from any type, sexual and emotional IPV. Having seen the father
      beating the mother was positively associated with most IPV subtypes, and having
      been diagnosed with a sexually transmitted infection (STI) in the previous 12
      months was associated with physical and sexual IPV. CONCLUSION: Significant rates
      of FGM and IPV were found among this sample of Ivorian women calling for the need
      for multiple strategies to reduce FGM and IPV.

PMID- 24451019
TI  - Immunoblotting of soluble antigens in Paracoccidioides brasiliensis culture.
AB  - This study investigated the major soluble antigens produced by Paracoccidioides
      brasiliensis (Pb339) cultured in solid Sabouraud (pH 5.6 and 8.5), Sabouraud plus
      brain heart infusion and liquid tomato juice-enriched complex medium media at
      intervals of 3 days over 30 days by immunoblotting and concluded that, to
      optimize the source of each antigen, both time and growth conditions should be
      considered. 

PMID- 24451018
TI  - A recall-by-genotype study of CHRNA5-A3-B4 genotype, cotinine and smoking
      topography: study protocol.
AB  - BACKGROUND: Genome-wide association studies have revealed an association between
      several loci in the nicotinic acetylcholine receptor gene cluster CHRNA5-A3-B4
      and daily cigarette consumption. Recent studies have sought to refine this
      phenotype, and have shown that a locus within this cluster, marked primarily by
      rs1051730 and rs16969968, is also associated with levels of cotinine, the primary
      metabolite of nicotine. This association remains after adjustment for self
      reported smoking, which suggests that even amongst people who smoke the same
      number of cigarettes there is still genetically-influenced variation in nicotine
      consumption. This is likely to be due to differences in smoking topography, that
      is, how a cigarette is smoked (e.g., volume of smoke inhaled per puff, number of
      puffs taken per cigarette). The aim of this study is to determine potential
      mediation of the relationship between the rs1051730 locus and cotinine levels by
      smoking topography. METHODS/DESIGN: Adopting a recall-by-genotype design, we will
      recruit 200 adults from the Avon Longitudinal Study of Parents and Children on
      the basis of minor or major homozygote status at rs1051730 (100 in each genotype
      group). All participants will be current, daily smokers. Our primary study
      outcome measures will be measures of smoking topography: total volume of smoke
      (ml) inhaled per cigarette, total volume of smoke (ml) inhaled over of the course
      of one day, and salivary cotinine level (ng/ml). DISCUSSION: This study will
      extend our understanding of the biological basis of inter-individual variability
      in heaviness of smoking, and therefore in exposure to smoking-related toxins. The
      novel recall-by-genotype approach we will use is efficient, maximising
      statistical power, and enables the collection of extremely precise phenotypic
      data that are impractical to collect in a larger sample. The methods described
      within this protocol also hold the potential for wider application in the field
      of molecular genetics.

PMID- 24451020
TI  - S100B as a potential biomarker for the detection of cytotoxicity of melanocytes.
AB  - Skin irritation is one of the most common adverse reactions in hydroquinone (HQ)
      and retinoic acid (RA). Although melanocytes have rarely been considered to be
      involved in skin irritation, RA and particularly HQ could induce melanocyte
      toxicity, resulting in depigmentation. We chose S100B as a candidate gene for
      melanocytotoxicity from a genome-wide transcriptional profiling analysis after
      applying irritant doses of HQ, RA and sodium lauryl sulphate (SLS) to cultures of
      keratinocytes and/or melanocytes. In this study, the role of S100B on melanocyte
      viability and cytotoxicity was examined. S100B was detected in melanocytes, but
      not in keratinocytes or fibroblasts. Melanocytes after treatment with increasing
      concentrations of HQ, RA, SLS and urushiol showed significant increases in
      intracellular and extracellular S100B expression with reduced viable cell number
      and increased release of lactate dehydrogenase. No RAGE expression and no
      significant function of CD166/ALCAM in melanocyte survival and cytotoxicity
      favoured the role of intracellular S100B in chemically irritated melanocytes.
      S100B knock-down increased apoptosis through inhibition of PI3K/AKT, NF-kappaB
      and ERK activation, suggesting the increased intracellular S100B expression by
      chemical irritation as a compensatory reaction to reduce cytotoxicity. The
      numerical decrease in S100B/c-kit-double-positive melanocytes was also examined
      in human skin epidermis irritated by HQ or RA with stronger staining intensities
      of S100B. Collectively, the decrease in viable cell number by reduced
      intracellular S100B levels in vitro and by chemical irritation in vivo suggests
      that S100B could be a potential biomarker for melanocytes cytotoxicity. 

PMID- 24451021
TI  - The so called "malignant fibrous histiocytoma" is actually an unusual
      fibrosarcoma.
AB  - The so-called "malignant fibrous histiocytoma (MFH)" has become progressively
      more enigmatic since entering the soft tissue tumor field, based on tissue
      culture studies performed almost 50 years ago. It inexplicably evolved from an
      exceedingly common soft tissue diagnosis into a problematic diagnosis. Because of
      the conundrum, clinicians require that "malignant fibrous histiocytoma", the name
      that they are familiar with, appears somewhere in the diagnosis. A recent review
      of the electron micrographs from 157 MFHs diagnosed over 32 years appears to
      explain how it was misnamed and its true identity, and as a consequence requires
      an updating of its clinico-pathologic correlation (CPC). It is an unusual
      fibroblastic entity that has the capacity to attract, activate, and stimulate
      fusion of normal macrophages.

PMID- 24451022
TI  - Influence of steric factors on chiral lithium amide aggregates.
AB  - The solution structures of three mixed aggregates dissolved in toluene-d8
      consisting of the lithiated amides derived from (S)-N-isopropyl-1
      ((triisopropylsilyl)oxy)propan-2-amine, (R)-N-(1-phenyl-2
      ((triisopropylsilyl)oxy)ethyl)propan-2-amine, or (S)-N-isobutyl-3-methyl-1
      ((triisopropylsilyl)oxy)butan-2-amine and n-butyllithium are characterized by
      various NMR experiments including diffusion-ordered NMR spectroscopy with
      diffusion coefficient-formula weight correlation analyses (D-FW) and other one-
      and two-dimensional NMR techniques. We report that steric hindrance of R1 and R2
      groups of the chiral lithium amide controls the aggregation state of the mixed
      aggregates. With a less hindered R2 group, lithium (S)-N-isopropyl-1
      ((triisopropylsilyl)oxy)propan-2-amide forms mostly a 2:2 ladder-type mixed
      aggregate with n-butyllithium. Increase of steric hindrance of the R1 and R2
      groups suppresses the formation of the 2:2 mixed aggregate and promotes formation
      of a 2:1 mixed aggregate. We observe that lithium (S)-N-isobutyl-3-methyl-1
      ((triisopropylsilyl)oxy)butan-2-amide forms both a 2:2 mixed aggregate and a 2:1
      mixed trimer with n-butyllithium. Further increase in the steric hindrance of R1
      and R2 groups results in the formation of only 2:1 mixed aggregate as observed
      with lithium (R)-N-(1-phenyl-2-((triisopropylsilyl)oxy)ethyl)propan-2-amide. 

PMID- 24451023
TI  - The efficacy of 3% minoxidil vs. combined 3% minoxidil and Korean red ginseng in
      treating female pattern alopecia.

PMID- 24451024
TI  - Probing of an adsorbate-specific excited state on an organic insulating surface
      by two-photon photoemission spectroscopy.
AB  - In this study, we investigate the photoexcited electronic states of ferrocene
      (Fc) molecules adsorbed on an organic insulating surface by two-photon
      photoemission spectroscopy. This insulating layer, composed of a decanethiolate
      self-assembled monolayer formed on an Au(111) substrate, enables us to probe the
      electronically excited states localized at the adsorbed Fc molecules. The
      adsorbate-specific state is resonantly excited by photons at 4.57 eV, which is
      0.5 eV smaller than the energy of the first molecular Rydberg state of free Fc in
      the gas phase. This result indicates that the electrons are bound to both the
      excited hole formed in the adsorbate and the positive image charge induced in the
      substrate. The hybridized electronic characteristics of the adsorbate-specific
      state are responsible for the strong transition selectivity and short lifetime of
      the excited state. 

PMID- 24451026
TI  - Survival analysis of high-intensity focused ultrasound therapy vs. transarterial
      chemoembolization for unresectable hepatocellular carcinomas.
AB  - BACKGROUND & AIMS: High-intensity focused ultrasound (HIFU) ablation is a non
      invasive treatment for unresectable hepatocellular carcinomas (HCCs), but long
      term survival analysis is lacking. This study was to analyse its outcome compared
      to that of transarterial chemoembolization (TACE). METHODS: From October 2003 to
      September 2010, 113 patients received HIFU ablation as a treatment of HCCs at our
      hospital. Twenty-six patients had HCCs sized 3-8 cm. Fifty-two patients with
      matched tumour characteristics having TACE as primary treatment were selected for
      comparison. Short-term outcome and long-term survival were analysed. RESULTS: In
      the HIFU group (n = 26), 46 tumours were ablated. The median age of the patients
      was 69 (49-84) years. The median tumour size was 4.2 (3-8) cm. In the TACE group
      (n = 52), the median age of the patients was 67 (44-84) years. The median tumour
      size was 4.8 (3-8) cm. There was no hospital mortality in any of the groups. In
      the HIFU group, the rates of complete tumour response, partial tumour response,
      stable disease and progressive disease were 50%, 7.7%, 25.6% and 7.7%
      respectively, according to the modified Response Evaluation Criteria in Solid
      Tumours. The TACE group had the corresponding rates at 0%, 21.2%, 63.5% and 15.4%
      respectively (P < 0.0001). The 1-year, 3-year and 5-year survival rates were
      84.6%, 49.2% and 32.3% respectively, in the HIFU group and 69.2%, 29.8% and 2.3%
      respectively, in the TACE group (P = 0.001). CONCLUSION: HIFU ablation is a safe
      and effective method for unresectable HCCs. A survival benefit is observed over
      sole TACE.

PMID- 24451027
TI  - Chromophore dynamics in the PYP photocycle from femtosecond stimulated Raman
      spectroscopy.
AB  - Femtosecond stimulated Raman spectroscopy (FSRS) is used to examine the
      structural dynamics of the para-hydroxycinnamic acid (HCA) chromophore during the
      first 300 ps of the photoactive yellow protein (PYP) photocycle, as the system
      transitions from its vertically excited state to the early ground state cis
      intermediate, I0. A downshift in both the C7?C8 and C1?O stretches upon
      photoexcitation reveals that the chromophore has shifted to an increasingly
      quinonic form in the excited state, indicating a charge shift from the phenolate
      moiety toward the C9?O carbonyl, which continues to increase for 170 fs. In
      addition, there is a downshift in the C9?O carbonyl out-of-plane vibration on an
      800 fs time scale as PYP transitions from its excited state to I0, indicating
      that weakening of the hydrogen bond with Cys69 and out-of-plane rotation of the
      C9?O carbonyl are key steps leading to photoproduct formation. HOOP intensity
      increases on a 3 ps time scale during the formation of I0, signifying distortion
      about the C7?C8 bond. Once on the I0 surface, the C7?C8 and C1?O stretches blue
      shift, indicating recovery of charge to the phenolate, while persistent intensity
      in the HOOP and carbonyl out-of-plane modes reveal HCA to be a cissoid structure
      with significant distortion about the C7?C8 bond and of C9?O out of the molecular
      plane. 

PMID- 24451025
TI  - Paracrine functions of fibrocytes to promote lung fibrosis.
AB  - Fibrocytes are derived from the bone marrow and are found in the circulation.
      They can be recruited to sites of injury and contribute to repair/remodeling. In
      vitro evidence suggests that fibrocytes may differentiate into fibroblasts to
      promote lung fibrosis. However, in vivo evidence for this is sparse. This review
      summarizes recent literature which may suggest that fibrocytes function to
      promote fibrosis via paracrine actions. In this way, secretion of growth factors,
      proteases and matricellular proteins may strongly influence the actions of
      resident epithelial and mesenchymal cells to promote repair and resolution or to
      tip the scale toward pathologic remodeling. 

PMID- 24451028
TI  - Plasma minichromosome maintenance complex component 6 is a novel biomarker for
      hepatocellular carcinoma patients.
AB  - AIM: This study aimed to investigate the presence of plasma minichromosome
      maintenance complex component 6 (MCM6) mRNA and protein levels in hepatocellular
      carcinoma (HCC) patients and evaluate their diagnostic value for HCC. METHODS:
      Blood samples were collected from 61 HCC and 29 cirrhotic patients, and 30
      healthy individuals. Circulating RNA was extracted from plasma of all samples.
      The mRNA for MCM6 were amplified and quantified by real-time polymerase chain
      reaction. Plasma MCM6 and alpha-fetoprotein (AFP) protein levels were measured by
      enzyme-linked immunosorbent assay. RESULTS: In HCC patients, MCM6 mRNA and
      protein levels were significantly increased over the cirrhotic and healthy
      controls. The levels of MCM6 mRNA and protein in the plasma of HCC patients
      correlated to vascular invasion (P < 0.01). Higher MCM6 protein levels also
      correlated with tumor stage progression and lymph node metastasis. The MCM6
      protein has sensitivity of 67.2% and specificity of 89.8% in differentiating
      total HCC from non-HCC individuals. In the AFP negative HCC group, MCM6 mRNA and
      protein could both detect 76.9% of HCC patients; combining the two of them
      increased the detection rate to 84.6%. In small HCC patients, MCM6 mRNA and
      protein could detect 64.3% and 71.4% of patients, respectively; combining AFP,
      MCM6 mRNA and MCM6 protein could detect 85.7% of small HCC patients. CONCLUSION:
      Our results suggest that MCM6 mRNA and protein levels in plasma can be promising
      independent biomarkers for HCC, especially in AFP negative and small HCC
      patients.

PMID- 24451029
TI  - About Brugada phenocopy: Brugada phenocopy with a flecainide overdose: a
      pharmacological dose effect?

PMID- 24451030
TI  - Morphology meets molecules: a new genus and two new species of diphyllidean
      cestodes from the Yellowspotted skate, Leucoraja wallacei, from South Africa.
AB  - Two morphologically disparate undescribed species of diphyllidean cestodes from
      the Yellowspotted skate, Leucoraja wallacei , from South Africa were included in
      a recent molecular phylogenetic study aimed at revising diphyllidean
      classification. From a molecular standpoint, these species were determined to be
      only distantly related to one another. One (originally referred to as
      Echinobothrium n. sp. 2) showed affinities with species of the batoid
      parasitizing Echinobothrium sensu stricto and is described here as Echinobothrium
      marquesi n. sp. This species most closely resembles Echinobothrium joshuai, an
      affinity supported by the previous molecular study, but differs in the form of
      its "B" hooks and degree of overlap between bothria and cephalic peduncle. The
      other species (originally referred to as New genus n. sp. 1), although exhibiting
      the full complement of scolex armature, grouped among primarily shark-hosted
      genera, most of which lack or exhibit reduced scolex armatures. That unexpected
      result suggested that erection of a novel genus might be warranted, but
      morphological grounds supporting the action were not apparent at that time. The
      present study aimed to explore the morphology of this taxon in more detail. Light
      and scanning electron microscopy revealed this taxon to be exceptional in that
      its lateral hooklets, which are arranged in 2 clusters like those of
      Echinobothrium and Coronocestus, are unique in being arranged in anterior and
      posterior rows, rather than in a single row. Andocadoncum n. gen. is erected,
      with Andocadoncum meganae n. sp. as its type, to accommodate this taxon. A minor
      adjustment to the existing hook formula by presenting counts for the anterior
      hooklets (a) separately from the posterior hooklets (b) readily accommodates this
      new form. Leucoraja wallacei is distinctive among skates in hosting 2 different
      genera of diphyllideans. In the context of the previous molecular phylogenetic
      analyses, it appears that the presence of Andocadoncum n. gen. in this skate
      species may be the result of a host-switching event involving a weakly or unarmed
      shark-hosted taxon moving to a batoid-a shift that was likely accompanied by a
      return to the fully armed condition seen, for example, in other batoid
      parasitizing members of the order.

PMID- 24451031
TI  - Synthesis of trans-2,6-disubstituted cyclohexanones through allylic substitution.
AB  - trans-2,6-Disubstituted cyclohexanones were synthesized with high regio- and
      stereoselectivity by allylic substitution followed by ozonolysis. Both alkyl and
      aryl groups were successfully installed to the cyclohexane ring. The
      stereochemistry of the SN2' products was determined to be controlled by the pre
      existing chirality on the ring. The present method is highlighted by the
      synthesis of enantiomerically enriched cyclohexanones. 

PMID- 24451032
TI  - Canakinumab for gout: a specific, patient-profiled indication.
AB  - The role of interleukin-1 (IL-1) in inflammation induced by crystals, and
      especially by monosodium urate crystals (MSUCs), has raised much interest in both
      basic and clinical investigation. Several drugs have been developed, and more are
      still in development, to block IL-1 driven inflammation, though to date only
      canakinumab (blocking IL-1beta) has been labelled, yet limited to the European
      Union, with a restricted indication to treat episodes of acute inflammation
      (EAIs) in patients with gout in whom other therapeutic choices are unacceptable.
      Other medications developed for IL-1 blocking, such as anakinra and rilonacept,
      have been tested in gout patients in clinical trials, but lack label approval and
      may be further restricted to orphan indication in gout. Notwithstanding, the use
      of IL-1 blockade to prevent EAIs in gout looks promising, but no drug has yet
      obtained approval for such an indication.

PMID- 24451033
TI  - A new approach to radial basis function approximation and its application to
      QSAR.
AB  - We describe a novel approach to RBF approximation, which combines two new
      elements: (1) linear radial basis functions and (2) weighting the model by each
      descriptor's contribution. Linear radial basis functions allow one to achieve
      more accurate predictions for diverse data sets. Taking into account the
      contribution of each descriptor produces more accurate similarity values used for
      model development. The method was validated on 14 public data sets comprising
      nine physicochemical properties and five toxicity endpoints. We also compared the
      new method with five different QSAR methods implemented in the EPA T.E.S.T.
      program. Our approach, implemented in the program GUSAR, showed a reasonable
      accuracy of prediction and high coverage for all external test sets, providing
      more accurate prediction results than the comparison methods and even the
      consensus of these methods. Using our new method, we have created models for
      physicochemical and toxicity endpoints, which we have made freely available in
      the form of an online service at http://cactus.nci.nih.gov/chemical/apps/cap.

PMID- 24451034
TI  - Microanalytical X-ray imaging of depleted uranium speciation in environmentally
      aged munitions residues.
AB  - Use of depleted uranium (DU) munitions has resulted in contamination of the near
      surface environment with penetrator residues. Uncertainty in the long-term
      environmental fate of particles produced by impact of DU penetrators with hard
      targets is a specific concern. In this study DU particles produced in this way
      and exposed to the surface terrestrial environment for longer than 30 years at a
      U.K. firing range were characterized using synchrotron X-ray chemical imaging.
      Two sites were sampled: a surface soil and a disposal area for DU-contaminated
      wood, and the U speciation was different between the two areas. Surface soil
      particles showed little extent of alteration, with U speciated as oxides U3O7 and
      U3O8. Uranium oxidation state and crystalline phase mapping revealed these oxides
      occur as separate particles, reflecting heterogeneous formation conditions.
      Particles recovered from the disposal area were substantially weathered, and
      U(VI) phosphate phases such as meta-ankoleite (K(UO2)(PO4) . 3H2O) were dominant.
      Chemical imaging revealed domains of contrasting U oxidation state linked to the
      presence of both U3O7 and meta-ankoleite, indicating growth of a particle
      alteration layer. This study demonstrates that substantial alteration of DU
      residues can occur, which directly influences the health and environmental
      hazards posed by this contamination.

PMID- 24451036
TI  - Combined treatment with sodium butyrate and PD153035 enhances keratinocyte
      differentiation.
AB  - Epidermal growth factor (EGF) receptor (EGFR) signalling is a critical
      determinant of keratinocyte proliferation and differentiation in both normal and
      diseased skin. Here we explore the effects of combined treatment with the
      differentiation-promoting agent sodium butyrate (SB) and the EGFR inhibitor
      (EGFRI) PD153035 on terminal differentiation of normal human epidermal
      keratinocytes (NHEKs). Cells treated with SB showed increased expression of the
      levels of mRNA and protein of the differentiation markers filaggrin and
      transglutaminase 1. Cotreatment with EGF significantly blunted these effects of
      SB. Combined treatment with SB and PD153035 alleviated these inhibitory actions
      of EGF, resulting in improved effects of decreased cell growth and increased
      terminal differentiation, relative to the individual treatments. These results
      indicate that the combined use of a differentiation-promoting agent and an EGFR
      inhibitor may offer an additional approach to the management of
      hyperproliferative skin diseases. 

PMID- 24451035
TI  - Opportunities and challenges for gut microbiome studies in the Indian population.
AB  - The gut microbiome is a complex ecosystem that affects the development,
      immunological responses and nutritional status of the host. Efforts are being
      made to unravel the complex interaction between the gut microbiome and host to
      have a greater understanding about its role in human health. Colonization of the
      gut by microbes begins at birth, but the succession and composition of the
      microbial community depends on a number of factors including, but not limited to,
      the age, diet, genetic composition, gender, geographic location, and health
      status of an individual. Therefore, inclusion of diverse human subjects in the
      study of the gut microbiome is indispensable. However, conducting such studies in
      India presents unique opportunities and challenges. The vast diversity in human
      genetic composition, dietary habits, and geographic distribution that exists in
      the Indian population adds to the complexity in understanding the gut microbiome.
      Gut microbiome-related studies from other parts of the world have reported a
      possible association of diseases such as obesity and diabetes with the human gut
      microbiome. In contrast, an in-depth assessment of risk factors associated with
      altered gut microbiome in such diseases in the Indian population is lacking.
      Studies including the Indian population may give insights into the association of
      the gut microbiome with various factors and diseases that may not be possible
      from studies on western populations. This review briefly discusses the
      significance of the gut microbiome on human health and the present status of gut
      microbiome studies in the Indian population. In addition, this review will
      highlight the unique opportunities and challenges for gut microbiome studies in
      the Indian population. 

PMID- 24451037
TI  - Detection of autofluorescent Mycobacterium chelonae in living zebrafish.
AB  - Mycobacterium chelonae is widespread in aquatic environments and can cause
      mycobacteriosis with low virulence in zebrafish. The risk of infection in
      zebrafish is exacerbated in closed-recirculating aquatic systems where rapidly
      growing mycobacteria can live on biofilms, as well as in zebrafish tissues. We
      have discovered a method of identifying and visualizing M. chelonae infections in
      living zebrafish using endogenous autofluorescence. Infected larvae are easily
      identified and can be excluded from experimental results. Because infection may
      reduce fertility in zebrafish, the visualization of active infection in
      contaminated eggs of transparent casper females simplifies screening. Transparent
      fish are also particularly useful as sentinels that can be examined periodically
      for the presence of autofluorescence, which can then be tested directly for M.
      chelonae.

PMID- 24451038
TI  - Adult and child automated immature granulocyte norms are inappropriate for
      evaluating early-onset sepsis in newborns.
AB  - AIM: Automated haematology analysers are increasingly being used. Normal ranges
      for automated immature granulocyte counts (IG%) are described in adults and
      children as <1%, but are not reported for newborns, who often have complete blood
      count with differential in evaluation for early-onset sepsis. Therefore, this
      study aimed to describe IG% during the first 48 hours of life (HOL) in newborns
      and determine the clinical factors affecting IG%. METHODS: We carried out
      retrospective chart reviews for newborns >=35 weeks gestational age with one or
      more complete blood count with differential in the first 48 HOL. Clinical history
      and automated haematology results were reviewed. RESULTS: Forty-seven of 215
      subjects had two or more complete blood counts within 48 h. In the first 48 HOL,
      IG% ranged from 0 to 8.4% (95th percentile 5.2%). At <12 h, 70% of samples had
      IG% >1%. IG% appears to decrease over time. Earlier hour of life and higher birth
      weight were independently associated with higher IG%. CONCLUSION: Immature
      granulocyte counts in newborns appeared to be higher than reported for other age
      groups. Use of adult and child norms for IG% would not be appropriate for
      newborns being evaluated for early-onset sepsis.

PMID- 24451039
TI  - Hierarchical hybrid organic-inorganic materials with tunable textural properties
      obtained using zeolitic-layered precursor.
AB  - Novel layered zeolitic organic-inorganic materials have been synthesized using a
      two-dimensional zeolite precursor IPC-1P prepared by a top-down approach from
      zeolite UTL. The formation of porous materials containing organic linkers or
      polyhedral oligomeric siloxane covalently bonded to zeolite layers in the
      interlayer space was confirmed by a variety of characterization techniques (N2/Ar
      sorption analysis, XRD, (29)Si and (13)C NMR, TEM). The organic-inorganic porous
      hybrids obtained by intercalation with silsesquioxane posessed layered morphology
      and contained large crystalline domains. The hybrids exhibited mesoporous or
      hierarchical micro-/mesoporous systems, stable up to 350  degrees C. Textural
      properties of the formed zeolitic organic-inorganic materials can be controlled
      by varying the linker or synthetic conditions over a broad range. Surface areas
      and pore volumes of synthesized hybrids significantly exceed those for parent
      zeolite UTL and corresponding swollen material; the amount of micropores
      increased with increasing rigidity and size of the organic linker in the order
      biphenyl > phenylene > ethanediyl. 

PMID- 24451040
TI  - The economic impact of acute coronary syndrome on length of stay: an analysis
      using the Healthcare Cost and Utilization Project (HCUP) databases.
AB  - OBJECTIVE: To assess the economic impact of initial and repeat hospitalizations
      associated with acute coronary syndrome (ACS) over 1 year (2009). DESIGN AND
      METHODS: National- and state-level data on length of stay (LOS) and related
      charges for ACS-associated hospital admissions were assessed using two Healthcare
      Utilization Project databases. The first, the Nationwide Inpatient Sample (NIS),
      provided clinical and resource use information from ~8 million hospital stays,
      representing a 20% stratified sample of ~40 million annual hospital stays in the
      US in 2009. The second, the State Inpatient Databases, provided 100% of inpatient
      data from nine states that included both patient age and linked information on
      multiple patient admissions within the same calendar year. For patients with
      repeat admissions, the LOS, primary diagnosis, and total charges between the
      first and subsequent admissions were evaluated. All patients>=18 years of age
      with at least one diagnosis of ACS, defined using the International
      Classification of Diseases, 9th Revision, were included (code 410.xx [except
      410.x2], 411.1x and 411.8x). Variables evaluated for each discharge included
      demographics, cardiovascular events and procedures, LOS, discharge status, and
      total charges. RESULTS: The NIS reported 1,437,735 discharges for ACS in 2009. In
      this dataset, mean LOS for an initial ACS event was 5.56 days. Patients>65 years
      of age had the highest numbers of admissions; this group also had the most
      comorbidities. Approximately 40% of ACS patients with data on repeat visits had
      more than one admission, >70% of these within 2 months of the primary discharge.
      Mean charges were $71,336 for the first admission and $53,290 for the second
      admission. CONCLUSION: Despite a variety of new therapies to prevent ACS, it
      remains a common condition. Better therapies are called for if the clinical and
      cost burden of ACS is to be alleviated.

PMID- 24451041
TI  - Mass spectrometry imaging: an expeditious and powerful technique for fast in situ
      lignin assessment in Eucalyptus.
AB  - Plant biomass has been suggested as an alternative to produce bioethanol. The
      recalcitrance of plant biomass to convert cellulose into simpler carbohydrates
      used in the fermentation process is partially due to lignin, but the standard
      methods used to analyze lignin composition frequently use toxic solvents and are
      laborious and time-consuming. MS imaging was used to study lignin in Eucalyptus,
      since this genus is the main source of cellulose in the world. Hand-cut sections
      of stems of two Eucalyptus species were covered with silica and directly analyzed
      by matrix-assisted laser sesorption ionization (MALDI)-imaging mass spectrometry
      (MS). Information available in the literature about soluble lignin subunits and
      structures were used to trace their distribution in the sections and using a
      software image a relative quantification could be made. Matrixes routinely used
      in MALDI-imaging analysis are not satisfactory to analyze plant material and were
      efficiently substituted by thin layer chromatography (TLC) grade silica. A total
      of 22 compounds were detected and relatively quantified. It was also possible to
      establish a proportion between syringyl and guaiacyl monolignols, characteristic
      for each species. Because of the simple way that samples are prepared, the MALDI
      imaging approach presented here can replace, in routine analysis, complex and
      laborious MS methods in the study of lignin composition. 

PMID- 24451042
TI  - Diagnosis of Noonan syndrome and related disorders using target next generation
      sequencing.
AB  - BACKGROUND: Noonan syndrome is an autosomal dominant developmental disorder with
      a high phenotypic variability, which shares clinical features with other rare
      conditions, including LEOPARD syndrome, cardiofaciocutaneous syndrome, Noonan
      like syndrome with loose anagen hair, and Costello syndrome. This group of
      related disorders, so-called RASopathies, is caused by germline mutations in
      distinct genes encoding for components of the RAS-MAPK signalling pathway. Due to
      high number of genes associated with these disorders, standard diagnostic testing
      requires expensive and time consuming approaches using Sanger sequencing. In this
      study we show how targeted Next Generation Sequencing (NGS) technique can enable
      accurate, faster and cost-effective diagnosis of RASopathies. METHODS: In this
      study we used a validation set of 10 patients (6 positive controls previously
      characterized by Sanger-sequencing and 4 negative controls) to assess the
      analytical sensitivity and specificity of the targeted NGS. As second step, a
      training set of 80 enrolled patients with a clinical suspect of RASopathies has
      been tested. Targeted NGS has been successfully applied over 92% of the regions
      of interest, including exons for the following genes: PTPN11, SOS1, RAF1, BRAF,
      HRAS, KRAS, NRAS, SHOC, MAP2K1, MAP2K2, CBL. RESULTS: All expected variants in
      patients belonging to the validation set have been identified by targeted NGS
      providing a detection rate of 100%. Furthermore, all the newly detected mutations
      in patients from the training set have been confirmed by Sanger sequencing.
      Absence of any false negative event has been excluded by testing some of the
      negative patients, randomly selected, with Sanger sequencing. CONCLUSION: Here we
      show how molecular testing of RASopathies by targeted NGS could allow an early
      and accurate diagnosis for all enrolled patients, enabling a prompt diagnosis
      especially for those patients with mild, non-specific or atypical features, in
      whom the detection of the causative mutation usually requires prolonged
      diagnostic timings when using standard routine. This approach strongly improved
      genetic counselling and clinical management.

PMID- 24451043
TI  - Vitamin D deficiency in patients with Behcet's disease.
AB  - BACKGROUND: Behcet's disease is an autoimmune, recurrent and multisystem disease.
      Vitamin D has immunomodulator role in immune system. So that vitamin D deficiency
      was reported in some autoimmune diseases. Behcet's disease as a Silk Road disease
      is common in Iran. The aim of this study was to detect the serum level of 25(OH)
      vitamin D in Behcet's patients and control group. METHODS: In this case-control
      study, 112 Behcet's patients as cases group and 112 healthy individuals as
      controls group were enrolled. Any subject on vitamin D supplement, steroid, and
      immunosuppressors during the last 6 months were excluded. The serum level of
      25(OH) vitamin D was measured in the two groups by ELISA method. The findings
      were compared via SPSS software. RESULTS: About 57% and 17% of Behcet's patients
      had vitamin D deficiency and insufficiency respectively. Vitamin D deficiency was
      significantly more common in controls than cases group (P < 0.001). Vitamin D
      levels were significantly lower in controls (P < 0.001). Age and sex did not have
      any confounding effect on the results. There was no significant relationship
      between disease duration, disease activity, Pathergy test, HLA-B5, and HLA-B51
      with vitamin D level in Behcet's patients. CONCLUSIONS: Vitamin D deficiency is
      common among Behcet's patients. However, our results revealed vitamin D
      deficiency was significantly more common in healthy controls in comparison with
      Behcet's cases.

PMID- 24451044
TI  - Clinical signs, treatment, and outcome in 15 cattle with sinonasal cysts.
AB  - OBJECTIVE: To evaluate clinical signs, diagnosis, treatment and outcome of cattle
      with sinonasal cysts. STUDY DESIGN: Case series. ANIMALS: Cattle (n = 15).
      METHODS: Medical records (2004-2011) of cattle with a fluid-filled mass in the
      nasal cavity, conchae, and/or paranasal sinuses were evaluated. Data retrieved
      and analyzed were reason of presentation, clinical signs, diagnostic techniques,
      surgical treatment, complications, and outcome. RESULTS: Common presenting
      clinical signs were abnormal respiratory noise, nasal discharge, and abnormal
      respiratory effort. Mean age of affected cattle was 21.7 months. In 9 animals,
      cysts were identified by endoscopy. Radiographic signs included a mass in the
      paranasal sinuses or conchae (13), nasal septum deviation (12), fluid lines (10),
      and bone atrophy (5). Ten cattle were treated surgically with osteoplastic flap
      techniques to gain access to the frontal or maxillary sinus (5), nasal extraction
      of the cyst under endoscopic control (3) or a combination of both techniques (2).
      Nine cattle returned to be productive members of their herd and had no recurrence
      (mean follow-up, 20.7 months). CONCLUSIONS: Sinonasal cysts should be considered
      as a primary differential diagnosis in cattle with abnormal respiratory noise,
      particularly in younger animals. Multiple cysts were common, which underlines the
      importance of a thorough preoperative examination using appropriate imaging
      modalities. Despite the often expansive nature of sinonasal cysts, the prognosis
      with surgical treatment was good.

PMID- 24451045
TI  - Soluble intracellular adhesion molecule, M30 and M65 as serum markers of disease
      activity and prognosis in cholestatic liver diseases.
AB  - AIM: Hepatic apoptosis is involved in the pathogenesis of immune-mediated liver
      diseases such as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and
      primary sclerosing cholangitis (PSC). The aim of our study was to quantify
      distinct markers of apoptosis in sera of patients with AIH, PBC and PSC, and to
      evaluate correlation with markers of disease activity and prognosis. METHODS:
      Sera of patients with AIH, PBC and PSC, and of healthy controls were collected
      and distinct cell death markers were quantified using a bead-based multiplex
      enzyme linked immunosorbent assay (soluble intracellular adhesion molecule
      [sICAM], macrophage migration inhibitory factor [MIF], soluble Fas [sFas],
      plasminogen activator inhibitor 1 [PAI-1]) or single enzyme-linked immunosorbent
      assays (DNAse, M30, M65). RESULTS: In comparison with healthy controls, the
      apoptotic markers sFas, sICAM (only in PSC patients), M30 and the cell death
      marker M65 were substantially elevated in sera of patients with immune-mediated
      liver diseases, whereas DNAse activity was reduced. Interestingly, patients with
      advanced PSC presented with higher levels of sICAM, M30 and M65 than patients
      with mild PSC. Regression analysis revealed correlations between serum levels of
      sICAM, M30 and M65 with the Mayo Risk Score for PSC, and of M65 with the Mayo
      Risk Score for PBC. CONCLUSION: Concentrations of the serum markers of apoptosis
      sFas and M30 and of the marker of total cell death M65 are elevated in patients
      with immune-mediated liver diseases, whereas activity of DNAse is reduced. In
      patients with PSC, sICAM, M30 and M65 may serve as indicators for disease
      activity and prognosis.

PMID- 24451046
TI  - Directed dispersal by rotational shepherding supports landscape genetic
      connectivity in a calcareous grassland plant.
AB  - Directed dispersal by animal vectors has been found to have large effects on the
      structure and dynamics of plant populations adapted to frugivory. Yet, empirical
      data are lacking on the potential of directed dispersal by rotational grazing of
      domestic animals to mediate gene flow across the landscape. Here, we investigated
      the potential effect of large-flock shepherding on landscape-scale genetic
      structure in the calcareous grassland plant Dianthus carthusianorum, whose seeds
      lack morphological adaptations to dispersal to animals or wind. We found a
      significant pattern of genetic structure differentiating population within grazed
      patches of three nonoverlapping shepherding systems and populations of ungrazed
      patches. Among ungrazed patches, we found a strong and significant effect of
      isolation by distance (r = 0.56). In contrast, genetic distance between grazed
      patches within the same herding system was unrelated to geographical distance but
      significantly related to distance along shepherding routes (r = 0.44). This
      latter effect of connectivity along shepherding routes suggests that gene flow is
      spatially restricted occurring mostly between adjacent populations. While this
      study used nuclear markers that integrate gene flow by pollen and seed, the
      significant difference in the genetic structure between ungrazed patches and
      patches connected by large-flock shepherding indicates the potential of directed
      seed dispersal by sheep across the landscape. 

PMID- 24451047
TI  - Self-care for minor illness.
AB  - AIM: To describe experiences with and knowledge of minor illness, self-care
      interventions used in minor illness and channels of information used when
      providing self-care for minor illness. BACKGROUND: Although minor illness is self
      limiting, symptoms can be substantial and have a great impact on the affected
      person's wellbeing. Possibilities to seek and find information about health and
      self-care have significantly increased through internet-based communities,
      forums, and websites. Still, a considerable number of consultations with general
      practitioners are for conditions that are potentially self-treatable. Seeking
      advanced care for minor illnesses is costly for society and can create discomfort
      for patients as they are down-prioritized at emergency departments. METHODS:
      Study participants were recruited randomly from the Swedish Address Register. A
      questionnaire was sent out, and the final sample included 317 randomly selected
      persons aged 18-80 and living in Sweden. FINDINGS: Having experienced a specific
      illness correlated with self-reported knowledge. Preferred self-care
      interventions differed between different conditions, but resting and self
      medicating were commonly used, along with consulting health care facilities.
      Compliance to advice was the highest for official information channels, and
      family members were a popular source of advice.

PMID- 24451048
TI  - Stimulation of dorsal root ganglia for the management of complex regional pain
      syndrome: a prospective case series.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic and progressive
      pain condition usually involving the extremities and characterized by
      sensorimotor, vascular, and trophic changes. Spinal cord stimulation (SCS) is an
      effective intervention for this condition, but is hampered by the technical
      challenges associated with precisely directing stimulation to distal extremities.
      Dorsal root ganglia (DRG) may be more effective as a physiological target for
      electrical modulation due to recruitment of the primary sensory neurons that
      innervate the painful distal anatomical regions. METHODS: Eleven subjects
      diagnosed with uni- or bilateral lower-extremity CRPS were recruited as part of a
      larger study involving chronic pain of heterogeneous etiologies. Quadripolar
      epidural leads of a newly developed neurostimulation system were placed near
      lumbar DRGs using conventional percutaneous techniques. The neurostimulators were
      trialed; 8 were successful and permanently implanted and programed to achieve
      optimal pain-paresthesia overlap. RESULTS: All 8 subjects experienced some degree
      of pain relief and subjective improvement in function, as measured by multiple
      metrics. One month after implantation of the neurostimulator, there was
      significant reduction in average self-reported pain to 62% relative to baseline
      values. Pain relief persisted through 12 months in most subjects. In some
      subjects, edema and trophic skin changes associated with CRPS were also mitigated
      and function improved. Neuromodulation of the DRG was able to provide excellent
      pain-paresthesia concordance in locations that are typically hard to target with
      traditional SCS, and the stimulation reduced the area of pain distributions.
      CONCLUSIONS: Neuromodulation of the DRG appears to be a promising option for
      relieving chronic pain and other symptoms associated with CRPS. The capture of
      discrete painful areas such as the feet, combined with stable paresthesia
      intensities independent of body position, suggests this stimulation modality may
      allow more selective and consistent targeting of painful areas than traditional
      SCS.

PMID- 24451050
TI  - Effect of neighbourhood deprivation and social cohesion on mental health
      inequality: a multilevel population-based longitudinal study.
AB  - BACKGROUND: The common mental disorders (CMDs) of anxiety and depression are the
      most common form of poor mental health in the general population. Evidence from
      the small number of previous cohort studies on the role of neighbourhood factors
      in mental health is inconclusive. We tested the hypothesis that high levels of
      neighbourhood social cohesion modify an adverse association between change in
      individual mental health and neighbourhood deprivation. METHOD: We carried out a
      longitudinal multilevel analysis using data from the Caerphilly Health and Social
      Needs Cohort Study with a 7-year follow-up (n = 4426; age range 18-74 years at
      baseline). Neighbourhood deprivation and neighbourhood social cohesion were
      assessed at baseline and change in mental health between follow-up and baseline
      was assessed using the five-item Mental Health Inventory (MHI-5). RESULTS:
      Residence in the most deprived neighbourhoods was negatively associated with
      change in mental health, after adjusting for baseline individual socio-economic
      risk factors and transitions in life events. This negative effect was
      significantly reduced in high social cohesion neighbourhoods. The predicted
      change in mental health score was calculated for the 10th and 90th centiles of
      the household low-income distribution. The difference between them was -2.8 in
      the low social cohesion group and 1.1 in the high cohesion group. The difference
      between the groups was 3.9 [95% confidence interval (CI) 0.2-7.6]. CONCLUSIONS:
      The public health burden of poor mental health and mental health inequality could
      potentially be reduced by strengthening social cohesion in deprived
      neighbourhoods. This offers a mechanism to address the adverse effect of
      neighbourhood deprivation on population mental health.

PMID- 24451051
TI  - An uncommon response to para-his pacing.

PMID- 24451053
TI  - Phylogenetic, ecological, and allometric correlates of cranial shape in Malagasy
      lemuriforms.
AB  - Adaptive radiations provide important insights into many aspects of evolution,
      including the relationship between ecology and morphological diversification as
      well as between ecology and speciation. Many such radiations include divergence
      along a dietary axis, although other ecological variables may also drive
      diversification, including differences in diel activity patterns. This study
      examines the role of two key ecological variables, diet and activity patterns, in
      shaping the radiation of a diverse clade of primates, the Malagasy lemurs. When
      phylogeny was ignored, activity pattern and several dietary variables predicted a
      significant proportion of cranial shape variation. However, when phylogeny was
      taken into account, only typical diet accounted for a significant proportion of
      shape variation. One possible explanation for this discrepancy is that this
      radiation was characterized by a relatively small number of dietary shifts (and
      possibly changes in body size) that occurred in conjunction with the divergence
      of major clades. This pattern may be difficult to detect with the phylogenetic
      comparative methods used here, but may characterize not just lemurs but other
      mammals. 

PMID- 24451054
TI  - Genetic incorporation of seven ortho-substituted phenylalanine derivatives.

PMID- 24451055
TI  - Kinetic trapping of metastable amino acid polymorphs.
AB  - Second harmonic generation (SHG) microscopy measurements indicate that inkjet
      printed racemic solutions of amino acids can produce nanocrystals trapped in
      metastable polymorph forms upon rapid solvent evaporation. Polymorphism impacts
      the composition, distribution, and physico-kinetic properties of organic solids,
      with energetic arguments favoring the most stable polymorph. In this study,
      unfavored noncentrosymmetric crystal forms were observed by SHG microscopy.
      Polarization-dependent SHG measurement and synchrotron X-ray microdiffraction
      analysis of individual printed drops are consistent with formation of homochiral
      crystal production. Fundamentally, these results provide evidence supporting the
      ubiquity of Ostwald's Rule of Stages, describing the hypothesized transitioning
      of crystals between metastable polymorphic forms in the early stages of crystal
      formation. Practically, the presence of homochiral metastable forms has
      implications on chiral resolution and on solid form preparations relying on rapid
      solvent evaporation. 

PMID- 24451061
TI  - Novel c.358C>T mutation of SOX9 gene in prenatal diagnosis of campomelic
      dysplasia.

PMID- 24451062
TI  - An in vitro biofilm model system maintaining a highly reproducible species and
      metabolic diversity approaching that of the human oral microbiome.
AB  - BACKGROUND: Our knowledge of microbial diversity in the human oral cavity has
      vastly expanded during the last two decades of research. However, much of what is
      known about the behavior of oral species to date derives from pure culture
      approaches and the studies combining several cultivated species, which likely
      does not fully reflect their function in complex microbial communities. It has
      been shown in studies with a limited number of cultivated species that early oral
      biofilm development occurs in a successional manner and that continuous low pH
      can lead to an enrichment of aciduric species. Observations that in vitro grown
      plaque biofilm microcosms can maintain similar pH profiles in response to
      carbohydrate addition as plaque in vivo suggests a complex microbial community
      can be established in the laboratory. In light of this, our primary goal was to
      develop a robust in vitro biofilm-model system from a pooled saliva inoculum in
      order to study the stability, reproducibility, and development of the oral
      microbiome, and its dynamic response to environmental changes from the community
      to the molecular level. RESULTS: Comparative metagenomic analyses confirmed a
      high similarity of metabolic potential in biofilms to recently available oral
      metagenomes from healthy subjects as part of the Human Microbiome Project. A time
      series metagenomic analysis of the taxonomic community composition in biofilms
      revealed that the proportions of major species at 3 hours of growth are
      maintained during 48 hours of biofilm development. By employing deep
      pyrosequencing of the 16S rRNA gene to investigate this biofilm model with
      regards to bacterial taxonomic diversity, we show a high reproducibility of the
      taxonomic carriage and proportions between: 1) individual biofilm samples; 2)
      biofilm batches grown at different dates; 3) DNA extraction techniques and 4)
      research laboratories. CONCLUSIONS: Our study demonstrates that we now have the
      capability to grow stable oral microbial in vitro biofilms containing more than
      one hundred operational taxonomic units (OTU) which represent 60-80% of the
      original inoculum OTU richness. Previously uncultivated Human Oral Taxa (HOT)
      were identified in the biofilms and contributed to approximately one-third of the
      totally captured 16S rRNA gene diversity. To our knowledge, this represents the
      highest oral bacterial diversity reported for an in vitro model system so far.
      This robust model will help investigate currently uncultivated species and the
      known virulence properties for many oral pathogens not solely restricted to pure
      culture systems, but within multi-species biofilms.

PMID- 24451064
TI  - Kinematic analysis of upper extremity movement during drinking in hemiplegic
      subjects.
AB  - BACKGROUND: It is necessary to analyze the kinematic properties of a paralyzed
      extremity to quantitatively determine the degree of impairment of hemiplegic
      people during functional activities of daily living (ADL) such as a drinking
      task. This study aimed to identify the kinematic differences between 16
      hemiplegic and 32 able-bodied participants in relation to the task phases when
      drinking with a cup and the kinematic strategy used during motion with respect to
      the gravity direction. METHODS: The subjects performed a drinking task that was
      divided into five phases according to Murphy's phase definition: reaching,
      forward transport, drinking, backward transport, and returning. We found that the
      groups differed in terms of the movement times and the joint angles and angular
      velocities of the shoulder, elbow, and wrist joints. FINDINGS: Compared to the
      control group, the hemiplegic participants had a larger shoulder abduction angle
      of at most 17.1 degrees  during all the phases, a larger shoulder flexion angle
      of 7.6 degrees  during the reaching phase, and a smaller shoulder flexion angle
      of 6.4 degrees  during the backward transporting phase. Because of these shoulder
      joint patterns, a smaller elbow pronation peak angle of at most 13.1 degrees  and
      a larger wrist extension peak angle of 12.0 degrees  were found in the motions of
      the hemiplegic participants, as compensation to complete the drinking task. The
      movement in the gravity direction during the backward transporting phase resulted
      in a 15.9% larger peak angular velocity for elbow extension in the hemiplegic
      participants compared to that of the control group. INTERPRETATION: These
      quantitative kinematic patterns help provide an understanding of the movements of
      an affected extremity and can be useful in designing rehabilitation robots to
      assist hemiplegic people with ADL.

PMID- 24451063
TI  - Toxicity assessment of air-delivered particle-bound polybrominated diphenyl
      ethers.
AB  - Human exposure to polybrominated diphenyl ethers (PBDEs) can occur via ingestion
      of indoor dust, inhalation of PBDE-contaminated air and dust-bound PBDEs.
      However, few studies have examined the pulmonary toxicity of particle-bound
      PBDEs, mainly due to the lack of an appropriate particle-cell exposure system. In
      this study we developed an in vitro exposure system capable of generating
      particle-bound PBDEs mimicking dusts containing PBDE congeners (BDEs 35, 47 and
      99) and delivering them directly onto lung cells grown at an air-liquid interface
      (ALI). The silica particles and particles-coated with PBDEs ranged in diameter
      from 4.3 to 4.5 MUm and were delivered to cells with no apparent aggregation.
      This experimental set up demonstrated high reproducibility and sensitivity for
      dosing control and distribution of particles. ALI exposure of cells to PBDE-bound
      particles significantly decreased cell viability and induced reactive oxygen
      species generation in A549 and NCI-H358 cells. In male Sprague-Dawley rats
      exposed via intratracheal insufflation (0.6 mg/rat), particle-bound PBDE
      exposures induced inflammatory responses with increased recruitment of
      neutrophils to the lungs compared to sham-exposed rats. The present study clearly
      indicates the potential of our exposure system for studying the toxicity of
      particle-bound compounds.

PMID- 24451066
TI  - Neural correlates of inhibitory control and visual processing in youths with
      attention deficit hyperactivity disorder: a counting Stroop functional MRI study.
AB  - BACKGROUND: Despite evidence of inhibitory control and visual processing
      impairment in attention deficit hyperactivity disorder (ADHD), knowledge about
      its corresponding alterations in the brain is still evolving. The current study
      used counting Stroop functional MRI and the Cambridge Neuropsychological Test
      Automated Battery (CANTAB) to investigate if brain activation of inhibitory
      control and visual processing would differ in youths with ADHD relative to
      neurotypical youths. METHOD: We assessed 25 youths with ADHD [mean age 10.9
      (s.d.=2.2) years] and 23 age-, gender- and IQ-matched neurotypical youths [mean
      age 11.2 (s.d.=2.9) years]. The participants were assessed by using the Wechsler
      Intelligence Scale for Children, third edition, and two tests from the CANTAB:
      rapid visual information processing (RVP) and pattern recognition memory (PRM)
      outside the scanner. RESULTS: Youths with ADHD showed more activation than
      neurotypical youths in the right inferior frontal gyrus [Brodmann area (BA) 45]
      and anterior cingulate cortex, which were correlated with poorer performance on
      the RVP test in the CANTAB. In contrast, youths with ADHD showed less activation
      than neurotypical youths in the left superior parietal lobule (BA 5/7), which was
      correlated with the percentage of correct responses on the PRM test in the
      CANTAB. CONCLUSIONS: Our findings suggest that youths with ADHD might need more
      inhibitory control to suppress interference between number and meaning and may
      involve less visual processing to process the numbers in the counting Stroop task
      than neurotypical youths.

PMID- 24451065
TI  - Elevated signal transducers and activators of transcription 1 correlates with
      increased C-C motif chemokine ligand 2 and C-X-C motif chemokine 10 levels in
      peripheral blood of patients with systemic lupus erythematosus.
AB  - INTRODUCTION: The present study examines the levels of recently reported
      biomarkers, adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand
      2 (CCL2), C-X-C motif chemokine 10 (CXCL10), signal transducers and activators of
      transcription 1 (STAT1), and miR-146a in systemic lupus erythematosus (SLE)
      patients over multiple visits. METHODS: Peripheral blood leukocytes were
      collected from 65 healthy donors and 103 SLE patients, 60 of whom had samples
      from 2 or more visits. Total RNA was isolated and analyzed for the expression of
      mRNA and microRNA using Taqman real time PCR assays. Relative expression of I-IFN
      signature genes, chemokines, and miR-146a were determined by the DeltaDeltaCT
      method. Results were correlated with clinical data and analyzed by
      Wilcoxon/Kruskal-Wallis test and Fisher's exact test. RESULTS: Levels of ADAR,
      CCL2, CXCL10, and STAT1 in SLE were significantly elevated compared with the
      healthy controls (P <0.0001). ADAR, CCL2, and CXCL10 showed significant
      correlation with IFN score in both healthy donors (P <0.0033) and SLE patients (P
      <0.0001). In SLE patients, miR-146a level was not significantly different from
      healthy controls nor correlated to the IFN score. Two STAT1 populations were
      identified: a low STAT1 and a high STAT1 group. High STAT1 patient visits
      displayed higher (P <=0.0020) levels of CCL2 and CXCL10 than the low STAT1
      patient visits. STAT1 levels correlated with IFN score in low STAT1 group but not
      in high STAT1 group. More importantly, high STAT1 levels appeared as an enhancer
      of CCL2 and CXCL10 as indicated by the significantly stronger correlation of CCL2
      and CXCL10 with IFN score in high STAT1 patient visits relative to low STAT1
      patient visits. CONCLUSION: Our data indicate a novel role for STAT1 in the
      pathogenesis of SLE as an expression enhancer of CCL2 and CXCL10 in SLE patients
      with high levels of STAT1. Future study is needed to examine the exact role of
      STAT1 in the etiology of SLE.

PMID- 24451067
TI  - Prevalence and management of atrial fibrillation in primary care: a case study.
AB  - AIM: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and
      a major predisposing risk factor for stroke. Current UK guidelines propose stroke
      risk stratification of AF patients. Anticoagulation with warfarin is recommended
      for high risk patients, whereas treatment with aspirin alone is advised for those
      at low risk. The aim of this audit was to review practice at our institution and
      ascertain if guidelines on AF treatment were being followed. METHODS: A
      retrospective review of all patients diagnosed with non-valvular AF in June 2010
      was undertaken. Patient records were reviewed to collect demographic and co
      morbidity data relevant to stroke risk stratification. This was subsequently used
      to stratify patients according to stroke-risk using the CHADS2 scoring system.
      The use of anticoagulation and anti-platelet medication as well as any documented
      reasons for the omission of anticoagulation in high risk patients was noted.
      RESULTS: The prevalence of non-valvular AF in our practice population was 1.5%
      (151/10,155); 70% (105/151) of AF patients were found to be at high risk of
      stroke; 36% (38/105) of high risk patients were not on anticoagulation and the
      majority (58%) of these patients had no clear reason documented for the omission
      of warfarin. Of the 15 patients at low risk of stroke, 12 (80%) were on warfarin.
      Seven (4.4%) of the 151 AF patients were on both warfarin and aspirin and six
      (4%) were on neither medication. The commonest documented reasons for omission of
      warfarin in the high risk group were dementia and a history of gastrointestinal
      bleeding. DISCUSSION: The lack of documentation on withholding a proven
      beneficial treatment in high risk patients could potentially leave physicians
      open to medico-legal scrutiny. Maintaining low risk patients on anticoagulation
      may expose them to unnecessary risk. We recommend the use of automated audit
      tools designed to improve compliance with national guidelines.

PMID- 24451068
TI  - Hepatic rupture: a rare but serious complication of HELLP syndrome.

PMID- 24451069
TI  - Determinants of condom use at sexual debut among young Vietnamese.
AB  - BACKGROUND AND AIMS: Condom use at sexual debut is associated with subsequent
      condom use and with decreased risk of sexually transmitted infections. There is a
      dearth of data on determinants of condom use at first sexual intercourse. We
      aimed to determine factors associated with condom use at first sexual intercourse
      before marriage among Vietnamese adolescents and youths. METHODS: The study
      involved the analysis of data from the Survey Assessment of Vietnamese Youth,
      2003, the first nationally representative survey of young people in Vietnam. The
      survey included 7584 adolescents and youths aged 14-25 years. In this study, data
      of 605 adolescents and youths who had engaged in premarital sex were analyzed for
      factors associated with condom use using descriptive analyses, and regression
      techniques, allowing for sampling weights, clustering and stratification.
      RESULTS: Of 605 adolescents and youths who had engaged in premarital sex, 28.6%
      reported condom use at first sexual intercourse. Condom use at sexual debut was
      less common in females than males [odds ratio (OR)=0.15; 95% confidence interval
      (95% CI)=0.07-0.30] and less common in those who experienced peer pressure to
      engage in social higher risk behaviors (OR=0.57; 95% CI=0.32-0.99). Condom use
      was more common if a friend/acquaintance or a stranger/sex worker was the first
      sexual partner (OR=2.20; 95% CI=1.16-4.17 and OR=17.90; 95% CI=6.88-46.54)
      respectively, each compared with fiance/boyfriend/girlfriend as first sexual
      partner. CONCLUSIONS: These data suggest that approximately one in three
      unmarried Vietnamese youths used a condom at first sexual intercourse. Gender,
      peer pressure and the nature of the relationship to the first sexual partner were
      independently associated with condom use. These results can inform programs
      directed at preventing HIV and other sexually transmitted infections among young
      Vietnamese.

PMID- 24451070
TI  - Lipid-based systems as a promising approach for enhancing the bioavailability of
      poorly water-soluble drugs.
AB  - Low oral bioavailability as a consequence of low water solubility of drugs is a
      growing challenge to the development of new pharmaceutical products. One of the
      most popular approaches of oral bioavailability and solubility enhancement is the
      utilization of lipid-based drug delivery systems. Their use in product
      development is growing due to the versatility of pharmaceutical lipid excipients
      and drug formulations, and their compatibility with liquid, semi-solid, and solid
      dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self
      microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems
      (SNEDDS) were explored in many studies as an efficient approach for improving the
      bioavailability and dissolution rate of poorly water-soluble drugs. One of the
      greatest advantages of incorporating poorly soluble drugs into such formulations
      is their spontaneous emulsification and formation of an emulsion, microemulsion
      or nanoemulsion in aqueous media. This review article focuses on the following
      topics. First, it presents a classification overview of lipid-based drug delivery
      systems and mechanisms involved in improving the solubility and bioavailability
      of poorly water-soluble drugs. Second, the article reviews components of lipid
      based drug delivery systems for oral use with their characteristics. Third, it
      brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often
      misused in literature, with special emphasis on the comparison between
      microemulsions and nanoemulsions.

PMID- 24451071
TI  - Liquisolid systems and aspects influencing their research and development.
AB  - Many modern drugs are poorly water soluble substances, which causes difficulties
      in the development of solid dosage forms with sufficient bioavailability.
      Preparation of liquisolid systems (LSS) is a novel technique for improving
      solubility, dissolution and bioavailability of such drugs. The basic principle of
      LSS preparation is conversion of the drug in liquid state into a free-flowing,
      compressible, dry powder through its absorption into suitable excipients - porous
      carriers (aluminometasilicates, microcrystalline cellulose), subsequently coated
      with material having high absorption capacity (silicon dioxide commonly known as
      colloidal silica). LSS exhibit advantages such as lower production costs compared
      to soft capsules, simple processing and enhanced drug release. The main benefit
      is higher bioavailability of the liquid drug, caused by a large surface area
      available for absorption. The article tries to clarify specific aspects connected
      with the formulation of LSS: properties of excipients (surface area, absorption
      capacity), variables related to the processing (solubility, liquid load factor)
      and dosage form evaluation.

PMID- 24451072
TI  - An in vitro based investigation into the cytotoxic effects of D-amino acids.
AB  - In the present study, cytotoxic effects of D-Ala, D-Pro and D-Lys are
      demonstrated. In an effort to study the possible mechanisms of the observed
      cytotoxicity, catalase activity, H2O2 generation, and apoptotic activity were
      measured in HeLa and MCF-7 cell lines. Although D-Lys is a poor substrate for DAO
      and therefore low H2O2 was detected, it was shown to provoke severe impairment of
      cellular integrity and survival. Interestingly, a very good substrate for DAO,
      such as D-Pro, did not substantially reduce cell viability. On the other hand, a
      moderate substrate for DAO, represented by D-Ala, was shown to moderately trigger
      toxicity in the tested cell lines. Although a correlation between the in vitro
      cytotoxicity of D-amino acids and the amount of H2O2 produced was absent, there
      was a good agreement between the ability of D-amino acids to trigger apoptosis
      and to provoke toxicity. Our results indicate that the toxicity of D-amino acids
      does not appear to be solely mediated by H2O2. Therefore, we hypothesize that
      other possible contributing apoptosis-mediated pathways might cause the observed
      toxicity.

PMID- 24451073
TI  - Preparation and evaluation of chitosan based thermoreversible gels for
      intraperitoneal delivery of 5-fluorouracil (5-FU).
AB  - Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate
      were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The
      formulation was evaluated for gelling characteristics and in vitro drug release.
      Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast
      cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino
      mice via intraperitoneal route and efficacy studies via intratumoral injections
      in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled
      reversibly in 8 min at 37  degrees C and provided prolonged release of the drug.
      Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while
      in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered
      intraperitoneally as the developed system. Tumor volume measurements showed
      comparable efficacy of 5-FU administered as gel and commercial injection with a
      greatly improved safety profile of the former as adjudged from mortality and body
      weight measurements.

PMID- 24451074
TI  - Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced
      cardiotoxicity in H9c2 myoblast cell line.
AB  - To investigate potential prevention or attenuation of anti- cancer drug induced
      cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was
      used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be
      cytotoxic for the H9c2 cell line with IC50 of 30.69 +/- 6.20 and 20.94 +/- 6.05
      mmol L-1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus
      IC50 could not be calculated. When 100 mmol L-1 doxorubicin was incubated for 72
      hours with 50 mmol L-1 diltiazem, 100 mmol L-1 dexrazoxane and 100 mmol L-1
      losartan, respectively, there was a 58.7 +/- 10.2, 52.2 +/- 11.7 and 44.7 +/- 5.4
      % reduction in cell death. When 200 mmol L-1 irinotecan was incubated for 72
      hours with 100 mmol L-1 dexrazoxane, losartan and diltiazem, respectively, a 27.7
      +/- 6.9, 25.6 +/- 5.1, and 19.1 +/- 2.3 % reduction in cell death was observed.
      Our data suggests that losartan and diltiazem were as effective as dexrazoxane in
      protecting the cells against irinotecan- and doxorubicin-induced cell toxicity.
      These findings offer potential uses of anti- -ischemic drugs for ablation of
      cytotoxicity in response to mitochondrial injury, thereby improving patient
      outcomes and reducing health-care costs.

PMID- 24451075
TI  - Chemical fingerprinting and quantitative analysis of two common Gleditsia
      sinensis fruits using HPLC-DAD.
AB  - Gleditsiae Fructus Abnormalis and Gleditsiae Sinensis Fructus are obtained from
      different developmental stages of fruits from Gleditsia sinensis Lam.
      (Leguminosae). The possible interchangeable usage of the two fruits, however, has
      long been very controversial. Here, high performance liquid chromatography
      coupled with diode array detection was developed to explore their chemical
      fingerprinting profiles. Besides, the amounts of aglycones of saponin compounds,
      echinocystic acid and oleanolic acid in both fruits were quantified. The results
      indicated that there was no significant difference in the content of aglycones
      from the two types of fruits. However, their chromatographic fingerprints showed
      distinct characteristics. Therefore, the interchangeable application of these
      fruits has to be taken with a specific precaution.

PMID- 24451076
TI  - Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle
      hydrogel for enhanced dermal delivery.
AB  - Coenzyme Q10 (Q10) loaded solid lipid nanoparticles (SLN) were prepared by the
      high speed homogenization method and incorporated into Carbopol 974P hydrogels.
      Compritol 888 ATO (C888) was employed as the lipid base; Poloxamer 188 (P188) and
      Tween 80 (Tw80) were used as surfactant and co-surfactant. Optimum particle size
      with narrow distribution was obtained as 152.2 nm for blank and 142.4 nm for Q10
      loaded SLNs. The overall charge of loaded SLNs was -13.7 +/- 1.3 mV. Q10
      entrapment efficiency was 89 % and the production yield was 94 %. Transmission
      electron microscopy analysis provided evidence of colloidal size, spherical shape
      while differential scanning calorimetry analysis confirmed recrystallization of
      the lipid after the preparation of SLNs. Trolox equivalent antioxidant capacity
      (TEAC) analysis has shown that antioxidant potential of Q10 can be protected in
      SLNs. Rheological characteristics demonstrated that the SLN incorporating gels
      were shear thinning and the mechanical strength of the gels was suitable for
      topical application. Diffusion studies from rat abdominal skin revealed that the
      delivery of Q10 was doubled in SLN incorporating gels, approximately 40 MUg cm-2,
      in comparison with gels prepared with only Q10 (not incorporated in SLNs). As a
      result, it can be stated that Q10-SLN loaded gels can be successful delivery
      systems for carrying Q10 efficiently into the skin without losing its antioxidant
      properties.

PMID- 24451077
TI  - Design and in vivo evaluation of emulgel formulations including green tea extract
      and rose oil.
AB  - Prevention of skin aging and its treatment is an emerging field for development
      of new formulations in cosmetics. Accordingly, plant extracts with antioxidant
      properties are beneficial cosmetic ingredients for this purpose. This study was
      aimed at developing a stable and easily manufactured emulgel including green tea
      extract and rose oil that is effective on the barrier function and hydration of
      the skin. An emulgel formulation containing 20 % green tea extract and 5 % rose
      oil was designed as a result of pre-formulation studies. Physicochemical
      characterization, in vitro stability studies, in vivo water content of the
      stratum corneum and transepidermal water loss studies were carried out
      afterwards. In vivo studies on ten female subjects were evaluated by using non
      invasive skin bioengineering techniques. Finally, a cosmetically acceptable,
      stable and effective emulgel formulation for skin barrier function with good
      hydrating properties was obtained for skin hydration, protection and anti-aging
      purposes.

PMID- 24451078
TI  - In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated
      salbutamol sulfate tablets.
AB  - The aim of this study was to investigate the in vitro and in vivo performance of
      salbutamol sulfate press-coated tablets for delayed release. The in vitro release
      behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100
      blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was
      examined. Morphological change of the press-coated tablet during in vitro release
      was recorded with a digital camera. Release of salbutamol sulfate from press
      coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8
      phosphate buffer solution. In vivo gamma scintigraphy study carried out on
      healthy men indicated that the designed system released the drug in lower parts
      of the GI tract after a lag time of 5 hours. The results showed the capability of
      the system of achieving delayed release of the drug in both in vitro and in vivo
      gamma scintigraphy studies.

PMID- 24451079
TI  - The content of fagopyrin and polyphenols in common and tartary buckwheat sprouts.
AB  - Dried buckwheat herb is used in medicinal products whereas fresh green plant
      parts, especially sprouts, are consumed as a vegetable. The herb contains
      fagopyrins, which cause sensitivity to light after ingestion. The aim of this
      study was to investigate the impact of different growing conditions and the
      development phase on the content of fagopyrin and phenolic compounds in buckwheat
      sprouts. Total flavonoid and total phenol contents, fagopyrin content and
      antioxidant activity were determined spectrophotometrically. Fagopyrin and
      flavonoids were located almost exclusively in cotyledons. Based on a comparison
      to hypericin toxicity, the recommendable intake of buckwheat sprouts was
      estimated to be less than 40 g per day.

PMID- 24451080
TI  - Molecular profiles of non-small cell lung cancers in cigarette smoking and never
      smoking patients.
AB  - PURPOSE: Molecular features of non-small cell lung cancer (NSCLC) in never
      smokers are not well recognized. We assessed the expression of genes potentially
      related to lung cancer etiology in smoking vs. never-smoking NSCLC patients.
      METHODS: We assayed frozen tumor samples from surgically resected 31 never
      smoking and 54 clinically pair-matched smoking NSCLC patients, and from
      corresponding normal lung tissue from 27 and 43 patients, respectively.
      Expression of 21 genes, including cell membrane kinases, sex hormone receptors,
      transcription factors, growth factors and others was assessed by reverse
      transcription - quantitative PCR. RESULTS: Expression of 5 genes was
      significantly higher in tumors of non-smokers vs. smokers: CSF1R (p<0.0001), RRAD
      (p<0.0001), PR (p=0.0004), TGFBR2 (p=0.0027) and EPHB6 (p=0.0033). Expression of
      AKR1B10 (p<0.0001), CDKN2A (p<0.0001), CHRNA6 (p<0.0001), SOX9 (p<0.0001),
      survivin (p<0.0001) and ER2 (p=0.002) was significantly higher in tumors compared
      to normal lung tissue. Expression of AR (p<0.0001), EPHB6 (p<0.0001), PR
      (p<0.0001), TGFBR2 (p<0.0001), TGFBR3 (p<0.0001), ER1 (p=0.0006) and DLG1
      (p=0.0016) was significantly lower in tumors than in normal lung tissue.
      Expression of IGF2 was higher in tumors than in healthy lung tissue in never
      smokers (p=0.003), and expression of AHR (p<0.0001), CSF1R (p<0.0001) and RRAD
      (p<0.0001) was lower in tumors than in healthy lung tissue in smokers.
      CONCLUSION: Expression of several genes in NSCLC is strongly related to smoking
      history. Lower expression of PR and higher expression of ER2 in tumors suggests a
      possibility of hormonal therapeutic intervention in selected NSCLC patients.
      Distinct molecular features of NSCLC in never-smokers, e.g. CHRNA6 upregulation,
      may prompt new treatment strategies.

PMID- 24451081
TI  - Seasonal variation in maternal and umbilical cord 25(OH) vitamin D and their
      associations with neonatal adiposity.
AB  - DESIGN: Neonatal body fat is an important indicator of foetal energy supply and
      growth with potential importance for long-term health. In this study, we wanted
      to explore seasonal variation of 25-hydroxy-vitamin D (25(OH)D) in maternal and
      umbilical cord plasma (UCP) to examine whether maternal and foetal 25(OH)D levels
      were associated with maternal BMI and neonatal fat mass (FM), and to explore the
      relationship among maternal and neonatal 25(OH)D levels, maternal glucose/insulin
      levels and UCP C-peptide. METHODS: An observational, prospective study of
      determinants of foetal growth and birth weight in healthy pregnant women. Total
      body composition in 202 newborns was measured by dual-energy X-ray
      absorptiometry. Circulating levels of biomarkers were assessed in mothers at
      gestational weeks 14-16 and 30-32 and UCP. RESULTS: The mean 25(OH)D
      concentration in UCP was significantly lower than in maternal circulation (31 vs
      45 nmol/l, P<0.001). Maternal and UCP 25(OH)D levels varied significantly with
      season. No significant association between maternal BMI (weeks 14-16) and UCP
      25(OH)D concentration was found. We found a strong positive association between
      maternal 25(OH)D and UCP 25(OH)D (P<0.001). There was no significant linear
      association between maternal BMI (weeks 14-16) and maternal 25(OH)D. We found no
      association between maternal 25(OH)D levels and glucose/insulin levels, nor with
      maternal or UCP 25(OH)D on UCP C-peptide levels. Finally, neonatal total body FM
      was positively associated with UCP 25(OH)D, P=0.02. CONCLUSIONS: We demonstrated
      seasonal variation in maternal and neonatal 25(OH)D levels at northern latitudes.
      UCP, but not maternal, 25(OH)D was a significant predictor of neonatal total FM.
      Maternal BMI and metabolic parameters such as glucose, insulin and UCP C-peptide
      levels were not associated with 25(OH)D in mothers or offspring.

PMID- 24451082
TI  - TSH measurement is not an appropriate screening test for autonomous functioning
      thyroid nodules: a retrospective study of 368 patients.
AB  - OBJECTIVE: Based on the assumption that normal TSH concentration rules out the
      presence of autonomous functioning thyroid nodules (AFTNs), clinical guidelines
      on the management of thyroid nodules only recommend a thyroid scan if TSH
      concentration is subnormal. However, the proportion of AFTN presenting with a
      normal TSH is unknown. Our objective is therefore to determine the proportion of
      AFTNs with a normal TSH level to ascertain whether a normal TSH really rules out
      an AFTN. DESIGN: Retrospective study on 368 patients with an AFTN. METHODS:
      Thyroid scans with a diagnosis of AFTN were reviewed retrospectively by one of us
      (R Moreno-Reyes), blinded to the clinical data. The diagnosis of solitary AFTN
      was confirmed in 368 patients. Among them, we selected 217 patients based on the
      absence of another thyroid nodule >10 mm, the absence of medical conditions able
      to interfere with thyroid function, and the completeness of the data. RESULTS:
      The proportion of AFTNs with normal TSH was 49%. This proportion increased to 71%
      in patients for whom thyroid scan was performed in the workup of a thyroid
      nodule. CONCLUSIONS: Our data suggest that serum TSH is not an effective
      screening tool to diagnose AFTNs. Using 'TSH-only' screening, as recommended by
      the majority of guidelines, the diagnosis of AFTN would have been missed in 71%
      of our patients in the workup of a thyroid nodule. Thyroid scan remains the gold
      standard for detecting AFTN and should be considered before performing fine
      needle aspiration cytology (FNAC), as the reliability of FNAC in an unsuspected
      AFTN remains unclear.

PMID- 24451084
TI  - Synthesis of CdS nanorod arrays and their applications in flexible piezo-driven
      active H2S sensors.
AB  - A flexible piezo-driven active H2S sensor has been fabricated from CdS nanorod
      arrays. By coupling the piezoelectric and gas sensing properties of CdS nanorods,
      the piezoelectric output generated by CdS nanorod arrays acts not only as a power
      source, but also as a response signal to H2S. Under externally applied
      compressive force, the piezoelectric output of CdS nanorod arrays is very
      sensitive to H2S. Upon exposure to 600 ppm H2S, the piezoelectric output of the
      device decreased from 0.32 V (in air) to 0.12 V. Such a flexible device can be
      driven by the tiny mechanical energy in our living environment, such as human
      finger pinching. Our research can stimulate a research trend on designing new
      material systems and device structures for high-performance piezo-driven active
      gas sensors.

PMID- 24451083
TI  - A theoretical framework for a virtual diabetes self-management community
      intervention.
AB  - Due to its high prevalence, chronic nature, potential complications, and self
      management challenges for patients, diabetes presents significant health
      education and support issues. We developed and pilot-tested a virtual community
      for adults with type 2 diabetes to promote self-management education and provide
      social support. Although digital-based programs such as virtual environments can
      address significant barriers to reaching patients (i.e., child care,
      transportation, location), they must be strongly grounded in a theoretical basis
      to be well-developed and effective. In this article, we discuss how we
      synthesized behavioral and virtual environment theoretical frameworks to guide
      the development of SLIDES (Second Life Impacts Diabetes Education and Support). 

PMID- 24451085
TI  - Designer phenethylamines routinely found in human urine: 2-ethylamino-1
      phenylbutane and 2-amino-1-phenylbutane.
AB  - 2-Ethylamino-1-phenylbutane (EAPB) and 2-amino-1-phenylbutane (APB) were
      identified by gas chromatography-mass spectrometry in multiple urine samples
      submitted for stimulant drug testing and screened positive for amphetamines by
      enzyme immunoassay. Forty-two samples from all over the USA were found,
      containing both analytes during a 3-month period May-July 2013. A sports dietary
      supplement 'CRAZE' has been determined to be one of the sources of EAPB supply.
      EAPB along with its suggested metabolite APB were detected in a urine sample,
      obtained from a person known to use 'CRAZE'. 

PMID- 24450891
TI  - Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease.
AB  - BACKGROUND: Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is
      in clinical development for the treatment of Alzheimer's disease. METHODS: We
      conducted two double-blind, randomized, placebo-controlled, phase 3 trials
      involving patients with mild-to-moderate Alzheimer's disease--one involving 1121
      carriers of the apolipoprotein E (APOE) epsilon4 allele and the other involving
      1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was
      administered by intravenous infusion every 13 weeks for 78 weeks. The primary
      outcome measures were scores on the 11-item cognitive subscale of the Alzheimer's
      Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher
      scores indicating greater impairment) and the Disability Assessment for Dementia
      (DAD, with scores ranging from 0 to 100 and higher scores indicating less
      impairment). A total of 1090 carriers and 1114 noncarriers were included in the
      efficacy analysis. Secondary outcome measures included findings on positron
      emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB
      PET) and cerebrospinal fluid phosphorylated tau (phospho-tau) concentrations.
      RESULTS: There were no significant between-group differences in the primary
      outcomes. At week 78, the between-group differences in the change from baseline
      in the ADAS-cog11 and DAD scores (bapineuzumab group minus placebo group) were 
      0.2 (P=0.80) and -1.2 (P=0.34), respectively, in the carrier study; the
      corresponding differences in the noncarrier study were -0.3 (P=0.64) and 2.8
      (P=0.07) with the 0.5-mg-per-kilogram dose of bapineuzumab and 0.4 (P=0.62) and
      0.9 (P=0.55) with the 1.0-mg-per-kilogram dose. The major safety finding was
      amyloid-related imaging abnormalities with edema among patients receiving
      bapineuzumab, which increased with bapineuzumab dose and APOE epsilon4 allele
      number and which led to discontinuation of the 2.0-mg-per-kilogram dose. Between
      group differences were observed with respect to PIB-PET and cerebrospinal fluid
      phospho-tau concentrations in APOE epsilon4 allele carriers but not in
      noncarriers. CONCLUSIONS: Bapineuzumab did not improve clinical outcomes in
      patients with Alzheimer's disease, despite treatment differences in biomarkers
      observed in APOE epsilon4 carriers. (Funded by Janssen Alzheimer Immunotherapy
      and Pfizer; Bapineuzumab 301 and 302 ClinicalTrials.gov numbers, NCT00575055 and
      NCT00574132, and EudraCT number, 2009-012748-17.).

PMID- 24451086
TI  - Estimation of equivalent cutoff thresholds in blood and oral fluid for drug
      prevalence studies.
AB  - Oral fluid is an easily available specimen for studying drug use in a cohort or
      population. The prevalence of drugs in samples of oral fluid is the same as the
      prevalence in blood if using equivalent cutoff concentrations. The cutoffs in
      oral fluid may be higher or lower than that in blood in accordance with the
      median oral fluid-to-blood (OF/B) concentration ratio, but it is also influenced
      by the skewness of the distribution of OF/B ratios. The aim of this study was to
      determine formulae for the estimation of equivalent cutoff concentrations in oral
      fluid and blood for 12 commonly used illegal and medicinal psychoactive drugs
      when oral fluid was collected with Statsure Saliva.SamplerTM. Paired samples from
      4,080 persons were collected and analyzed with chromatographic methods and mass
      spectroscopic detection. Regression formulae for the concentrations corresponding
      to selected percentiles in oral fluid versus the same concentration percentiles
      in blood were determined. The accuracy when multiplying the cutoff thresholds in
      blood with the average and median OF/B ratios to estimate equivalent cutoffs in
      oral fluid was also investigated. Prevalence regression gave the most accurate
      results. The regression formulae can be used to estimate equivalent cutoff
      concentrations in oral fluid and blood.

PMID- 24451087
TI  - HIV Infection is associated with compositional and functional shifts in the
      rectal mucosal microbiota.
AB  - BACKGROUND: Regardless of infection route, the intestine is the primary site for
      HIV-1 infection establishment and results in significant mucosal CD4+ T
      lymphocyte depletion, induces an inflammatory state that propagates viral
      dissemination, facilitates microbial translocation, and fosters establishment of
      one of the largest HIV reservoirs. Here we test the prediction that HIV infection
      modifies the composition and function of the mucosal commensal microbiota.
      RESULTS: Rectal mucosal microbiota were collected from human subjects using a
      sponge-based sampling methodology. Samples were collected from 20 HIV-positive
      men not receiving combination anti-retroviral therapy (cART), 20 HIV-positive men
      on cART and 20 healthy, HIV-negative men. Microbial composition of samples was
      analyzed using barcoded 16S Illumina deep sequencing (85,900 reads per sample
      after processing). Microbial metagenomic information for the samples was imputed
      using the bioinformatic tools PICRUST and HUMAnN. Microbial composition and
      imputed function in HIV-positive individuals not receiving cART was significantly
      different from HIV-negative individuals. Genera including Roseburia, Coprococcus,
      Ruminococcus, Eubacterium, Alistipes and Lachnospira were depleted in HIV
      infected subjects not receiving cART, while Fusobacteria, Anaerococcus,
      Peptostreptococcus and Porphyromonas were significantly enriched. HIV-positive
      subjects receiving cART exhibited similar depletion and enrichment for these
      genera, but were of intermediate magnitude and did not achieve statistical
      significance. Imputed metagenomic functions, including amino acid metabolism,
      vitamin biosynthesis, and siderophore biosynthesis differed significantly between
      healthy controls and HIV-infected subjects not receiving cART. CONCLUSIONS: HIV
      infection was associated with rectal mucosal changes in microbiota composition
      and imputed function that cART failed to completely reverse. HIV infection was
      associated with depletion of some commensal species and enrichment of a few
      opportunistic pathogens. Many imputed metagenomic functions differed between
      samples from HIV-negative and HIV-positive subjects not receiving cART, possibly
      reflecting mucosal metabolic changes associated with HIV infection. Such
      functional pathways may represent novel interventional targets for HIV therapy if
      normalizing the microbial composition or functional activity of the microbiota
      proves therapeutically useful.

PMID- 24451089
TI  - Is all chronic kidney disease created equal?
AB  - PURPOSE OF REVIEW: Chronic kidney disease (CKD) has generally been characterized
      functionally as a glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2,
      without accounting for cause, signs of structural damage, or relative risk of
      sequelae. Recently released guidelines define CKD as abnormalities of kidney
      structure or function, present for more than 3 months. We review the recent
      literature about CKD and its implications for renal surgery. RECENT FINDINGS:
      Most estimates of GFR are based on serum creatinine, after adjusting for age,
      race, sex, and/or body mass. Recent research indicates that many individuals have
      GFR values less than 60 ml/min/1.73 m2 without other manifestations of CKD.
      Nephron loss due to normal aging or renal surgery (CKD-S) may have lower
      likelihood of CKD progression, and may infer better survival, compared to
      individuals with the same degree of CKD due to medical causes. Patients with mild
      and moderate CKD due to surgical nephron loss may benefit from an alternative
      measurement method of renal function such as cystatin-C-derived or directly
      measured GFR. SUMMARY: CKD includes a diverse group of individuals with reduced
      GFR from a variety of causes. Classification of CKD according to GFR,
      albuminuria, and cause, may improve the management of patients with reduced GFR,
      as some causes (e.g., nephrectomy and aging) appear to be associated with a
      relatively low risk of progression.

PMID- 24451088
TI  - Sterilization of endoscopic instruments.
AB  - PURPOSE OF REVIEW: Sterilization of endoscopic instruments is an important but
      often ignored topic. The purpose of this article is to review the current
      literature on the sterilization of endoscopic instruments and elaborate on the
      appropriate sterilization practices. RECENT FINDING: Autoclaving is an economic
      and excellent method of sterilizing the instruments that are not heat sensitive.
      Heat sensitive instruments may get damaged with hot sterilization methods.
      Several new endoscopic instruments such as flexible ureteroscopes, chip on tip
      endoscopes, are added in urologists armamentarium. Many of these instruments are
      heat sensitive and hence alternative efficacious methods of sterilization are
      necessary. Although ethylene oxide and hydrogen peroxide are excellent methods of
      sterilization, they have some drawbacks. Gamma irradiation is mainly for
      disposable items. Various chemical agents are widely used even though they
      achieve high-level disinfection rather than sterilization. This article reviews
      various methods of endoscopic instrument sterilization with their advantages and
      drawbacks. SUMMARY: If appropriate sterilization methods are adopted, then it not
      only will protect patients from procedure-related infections but prevent
      hypersensitive allergic reactions. It will also protect instruments from damage
      and increase its longevity.

PMID- 24451094
TI  - Device-associated nosocomial infection rates and distribution of antimicrobial
      resistance in a medical-surgical intensive care unit in Turkey.
AB  - The aim of this study was to explore the rate of device-associated nosocomial
      infections (DANIs) and the distributions of causative agents and patterns of
      antibiotic resistance in the medical-surgical intensive care unit (ICU) over a 3
      year period and to compare these rates with those reported by National Nosocomial
      Infections Surveillance System and International Nosocomial Infection Control
      Consortium. A total of 1,798 patients were hospitalized in our ICU for 13,942
      days, of which 309 patients had DANIs, indicating an overall infection rate of
      22.1 per 1,000 ICU-days. The central line-associated bloodstream infection rate
      was 6.4 per 1,000 catheter-days, whereas the ventilator-associated pneumonia rate
      was 14.3 per 1,000 ventilator-days and the catheter-associated urinary tract
      infection rate was 4.3 per 1,000 catheter-days. Overall, 87.4% of all
      Staphylococcus aureus DANIs were caused by methicillin-resistant strains. With
      respect to Pseudomonas aeruginosa, 30.9% of the strains were resistant to
      ciprofloxacin, 23.3% to amikacin, 43.1% to ceftazidime, 19.1% to piperacillin
      tazobactam, and 34.7% to imipenem. Furthermore, 1.9% of the Enterococcus spp.
      were resistant to vancomycin, and 51.1% of Enterobacteriaceae were resistant to
      ceftriaxone. DANI rates decreased over the 3-year study period, which was likely
      in response to the infection control measures implemented in our ICU. 

PMID- 24451090
TI  - Robotic inferior vena cava thrombus surgery: novel strategies.
AB  - PURPOSE OF REVIEW: Kidney cancer is associated with renal vein or inferior vena
      cava (IVC) thrombus in up to 10% of cases. The management of these cases is
      complex, and thus typically performed open surgically. At selected institutions,
      the robotic approach is being explored. We review the literature on robotic IVC
      surgery. RECENT FINDINGS: Over the past 15 years, minimally invasive thrombectomy
      has been reported in 78 patients in the literature, including level I (67%),
      level II (30%) and level III (3%) thrombi. Of these, 91% involved hand-assisted
      or straight laparoscopic surgery, occasionally combined with open surgery for the
      IVC control aspect of the procedure. Only nine robotic cases have been reported
      in the literature to date, including level I (n=4) and high level thrombi.
      Additionally, we are developing novel strategies to advance robotic surgery for
      level II and level III thrombi. SUMMARY: Robotic surgery for selected level I and
      II caval thrombi is feasible. Further, clinical experience is necessary to
      determine the appropriate place of robotic surgery in managing these complex
      patients with caval involvement.

PMID- 24451095
TI  - Mutant murine hepatitis virus-induced apoptosis in the hippocampus.
AB  - The mutant virus Mu-3 was isolated from the soluble receptor-resistant mutant 7
      virus (srr7), which is a neuropathogenic strain of the mouse hepatitis virus
      JHMV, and cloned as a soluble receptor-resistant mutant from the highly
      neuropathogenic JHMV strain cl-2 virus (cl-2). In order to identify specific
      characteristics of Mu-3, the pathology of Mu-3-infected mice was compared with
      that of srr7- and cl-2-infected mice. The neuropathology after Mu-3 infection
      exhibited a mixed pattern comparable to that induced by srr7 and cl-2 infections.
      In addition, Mu-3 infection caused marked apoptotic lesions in the hippocampal
      region, particularly in the CA2 and CA3 subregions, in the brains of all infected
      mice. In contrast, in cl-2 infection, 10-20% of the infected mice exhibited
      apoptosis in the hippocampus, which was primarily observed in the CA1 subregion.
      Apoptosis also occurred in the pyramidal neurons and CD11b-bearing cells. The
      apoptotic cells, indicated by caspase 3-activation, were a mixed population of
      infected and a higher number of uninfected cells. These data indicated that
      apoptosis observed in Mu-3 infection could be induced by the indirect effects of
      infection in addition to direct effects of the infected cells occurring in a cell
      autonomous manner.

PMID- 24451091
TI  - Retrograde intrarenal surgery for kidney stones larger than 2.5 cm.
AB  - PURPOSE OF REVIEW: The management of large intrarenal stones (>2 cm) is typically
      percutaneous nephrolithotomy. Although the stone-free rate (SFR) of such a
      procedure is high (up to 95%), the complications related mainly to the renal
      access are sometimes a concern. Because of the evolution in technology, it is
      nowadays possible to treat intrarenal stones with retrograde intrarenal surgery.
      It remains unclear weather or not retrograde intrarenal surgery (RIRS) may be
      effective also for the treatment of larger stones (>2 cm). The purpose of this
      review is to provide recent data on the ureteroscopic management of kidney stones
      larger than 2.5 cm. RECENT FINDINGS: A systematic review of the literature for
      studies identified between January 2000 and September 2013 was performed. Only
      English language articles reporting on more than 10 cases treated with RIRS for
      intrarenal stones larger than 2.5 cm were considered for this review.Particular
      emphasis was given to studies published within the last 12 months. Of the 324
      studies identified, only 10 were considered suitable for this review. There were
      a total of 441 patients with a mean stone size of 2.9 cm. The SFR with an average
      of 1.6 procedures was 89.3%. The overall complication rate was 8% with major
      complication rate of 1.9%. SUMMARY: Although not supported by high evidence
      because of the absence of prospective randomized studies, it appears that in
      selected patients with large intrarenal stones, RIRS and laser lithotripsy may
      offer an acceptable efficacy with low morbidity.

PMID- 24451093
TI  - A cross-sectional survey of severe fever with thrombocytopenia syndrome virus
      infection of domestic animals in Laizhou City, Shandong Province, China.
AB  - A serosurvey of severe fever with thrombocytopenia syndrome virus (SFTSV)
      infection in domestic animals was conducted in the rural areas of Laizhou City,
      Shandong Province, China to determine strategies for control and prevention of
      SFTS. Serum samples were collected from cattle, goats, dogs, pigs, and chickens
      and antibodies against SFTSV were detected by double-antigen sandwich enzyme
      linked immunosorbent assay (ELISA). Of 641 serum samples, the SFTSV seropositive
      rate was 41.8% (268/641): 74.8%, 57.1%, 52.1%, 35.9%, and 0%, for goats, cattle,
      dogs, chickens, and pigs, respectively. We also found that the SFTSV seropositive
      rates were high among the aged cattle, goats, dogs, and chickens. SFTSV
      infections existed among cattle, goats, dogs, and chickens in Laizhou City, and
      goats had the highest seroprevalence. SFTSV seroprevalence increased with an
      increase in age among animals. To control of animal infestation with ticks may
      prevent human SFTSV infections. 

PMID- 24451098
TI  - Reducing the delay in initiation of treatment improved clinical outcomes in
      patients with imported malaria.
AB  - Although imported malaria poses a grave public health threat in Japan, diagnostic
      methods and disease management among patients and primary care providers has
      rarely been reported. Here, we retrospectively reviewed medical records of
      patients diagnosed with imported malaria in our hospital from 1991 to 2010.
      Thirty-four malaria cases were identified, corresponding to approximately 2% of
      the total number of cases in Japan. Falciparum malaria has become predominant in
      the last 2 decades, and compared with patients in the earlier decade (1991-2000),
      patients in the latter decade (2001-2010) showed significantly shorter delays in
      consulting medical facilities. The overall hospital delay also tended to be
      shorter in the latter decade, although delayed referral of patients by a week or
      more was still observed in more than one-third of the cases. The prevalence of
      risk factors for severe malaria among patients on the day of the referral visit
      was also lower in the latter decade. Further, the number of WHO-defined cases of
      severe malaria was smaller, and the length of the hospital stay was not prolonged
      during that decade. These findings indicated that a shorter delay in seeking
      medical treatment could reduce the risks of severe malaria. 

PMID- 24451092
TI  - Standards for prostate biopsy.
AB  - PURPOSE OF REVIEW: A variety of techniques have emerged for the optimization of
      prostate biopsy. In this review, we summarize and critically discuss the most
      recent developments regarding the optimal systematic biopsy and sampling labeling
      along with multiparametric MRI and magnetic resonance-targeted biopsies. RECENT
      FINDINGS: The use of 10-12-core-extended sampling protocols increases cancer
      detection rates compared with traditional sextant sampling and reduces the
      likelihood that patients will require a repeat biopsy, ultimately allowing more
      accurate risk stratification without increasing the likelihood of detecting
      insignificant cancers. As the number of cores increases above 12 cores, the
      increase in diagnostic yield becomes marginal. However, the limitations of this
      technique include undersampling, oversampling, and the need for repetitive
      biopsy. MRI and magnetic resonance-targeted biopsies have demonstrated
      superiority over systematic biopsies for the detection of clinically significant
      disease and representation of disease burden, while deploying fewer cores and may
      have applications in men undergoing initial or repeat biopsy and those with low
      risk cancer on or considering active surveillance. SUMMARY: A 12-core systematic
      biopsy that incorporates apical and far-lateral cores in the template
      distribution allows maximal cancer detection, avoidance of a repeat biopsy while
      minimizing the detection of insignificant prostate cancers. MRI-guided prostate
      biopsy has an evolving role in both initial and repeat prostate biopsy
      strategies, as well as active surveillance, potentially improving sampling
      efficiency, increasing the detection of clinically significant cancers, and
      reducing the detection of insignificant cancers.

PMID- 24451096
TI  - An epidemiological study of Mycoplasma genitalium infections among males
      attending a sexually transmitted disease clinic in Guangxi, China.
AB  - The objective of this study was to determine the prevalence of urethral
      Mycoplasma genitalium infections among male patients attending a sexually
      transmitted disease (STD) clinic in China and identify risk factors associated
      with this disease. A total of 423 patients were recruited in Hezhou City, Guangxi
      Province, China, and each was requested to complete a questionnaire regarding
      sociological and sexual behaviors. First-void urine samples were collected for M.
      genitalium analysis by polymerase chain reaction. Of the 406 urine samples
      collected, 114 were M. genitalium-positive, giving a prevalence rate of 28.1%.
      Univariate logistic regression analysis showed that M. genitalium infection was
      associated with younger age, having received at least senior high school
      education, and single marital status. In both univariate and multivariate
      logistic regression analyses, M. genitalium infection was found to be associated
      with lack of symptoms for STD in the past year (adjusted odds ratio [AOR] =
      2.839; 95% CI = 1.495-5.392; P = 0.001), no use of condoms with steady partners
      in the past year (AOR = 2.830; 95% CI = 1.468-5.455; P = 0.002), and having
      sexual encounters with female sexual workers within the past 3 months (AOR =
      2.955; 95% CI = 1.637-5.336; P < 0.0003). The observed high rate of M. genitalium
      infection among male STD patients in Hezhou City indicates an M. genitalium
      epidemic in the study population; thus, the national surveillance program and
      clinical health providers in China should more closely monitor this disease. 

PMID- 24451097
TI  - Plasma oxidative stress and total thiol levels in Crimean-Congo hemorrhagic
      fever.
AB  - In this study, we investigated the pro- and antioxidant status of patients with a
      pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) in terms of their role in
      its pathogenesis. During the study period, 34 children and 41 adults were
      diagnosed with CCHF. The control group consisted of healthy age- and gender
      matched children and adults. Serum levels of the total antioxidant capacity
      (TAC), total oxidant status (TOS), oxidative stress index (OSI), and plasma total
      thiol (TTL) were evaluated and compared between groups. The difference in mean
      TAC values between CCHF patients and healthy controls was not statistically
      significant (P > 0.05). Mean TOS, OSI, and TTL values were significantly lower in
      CCHF patients than in healthy controls (P < 0.001). Comparisons between the 2
      groups revealed that mean TOS and OSI values were significantly lower in adults
      with CCHF than in their healthy counterparts (P < 0.001). Similarly, mean TTL
      levels were lower in both children and adults with CCHF when compared separately
      with healthy controls (P < 0.05). There was no significant difference in the mean
      serum TTL levels between children and adults with CCHF (P > 0.05). Our results
      suggest that TTL may play a more important role in CCHF pathogenesis than the
      other parameters investigated. The mean TOS and OSI values were higher in the
      control group than in CCHF patients. 

PMID- 24451099
TI  - Comparisons of clinical characteristics between adult patients with 2009 H1N1
      influenza and those with seasonal influenza during the 2009 epidemic in Thailand.
AB  - Clinical presentations of patients with 2009 H1N1 influenza are generally similar
      to those of patients with seasonal influenza. A cross-sectional study was
      conducted among adults at an outpatient clinic in a university hospital setting
      during the 2009 epidemic. Infections in all patients were confirmed by real-time
      reverse transcription-polymerase chain reaction. There were 269 patients with
      2009 H1N1 influenza and 128 patients with seasonal influenza. Compared with
      patients with seasonal influenza, patients with 2009 H1N1 influenza were more
      likely to be aged <20 years (25.7% vs. 8.6%, P < 0.001) and to be students (38.7%
      vs. 22.0%, P = 0.001), or healthcare workers (20.1% vs. 10.9%, P = 0.022);
      however, they were less likely to have an underlying disease (25.6% vs. 39.8%, P
      = 0.004) and influenza vaccination (4.2% vs. 12.2%, P = 0.021). There were no
      differences in the illness duration, vital signs, and symptoms between groups.
      Patients with seasonal influenza were more likely to be admitted to the intensive
      care unit (2.4% vs. 0%, P = 0.033) and exhibited a higher mortality rate (2.4%
      vs. 0%, P = 0.093). A history of contact with a confirmed 2009 H1N1 influenza
      case (odds ratio [OR] = 12.91, P < 0.001) and age (OR = 1.05 per 10 years
      younger, P = 0.015) were associated with 2009 H1N1 influenza infections. In
      conclusion, these results showed differences in characteristics between the
      patients with 2009 H1N1 influenza and those with seasonal influenza. 

PMID- 24451100
TI  - Changes in Streptococcus pneumoniae serotypes in the nasopharynx of Japanese
      children after inoculation with a heptavalent pneumococcal conjugate vaccine.
AB  - In this study, we prospectively investigated changes in Streptococcus pneumoniae
      serotypes among Japanese children after heptavalent pneumococcal conjugate
      vaccine (PCV7) inoculation. We acquired nasopharyngeal swabs from the children at
      each routine PCV7 inoculation and again at least 2 months after the last PCV7
      inoculation. We defined 2 periods with regard to each culture: the inoculation
      period as "the period of pre- or incomplete vaccination" and post-inoculation as
      "the period of post- or completed vaccination." The prevalence of vaccine-type
      (VT) pneumococci was significantly reduced from 9.5% in the inoculation-period
      cultures to 2.9% in the post-inoculation cultures (P < 0.01). There was no
      statistical difference in the prevalence of non-vaccine-type pneumococci between
      the inoculation-period and post-inoculation cultures (24.1% versus 23.4%). The
      protection of PCV7 against nasopharyngeal colonization was inferred from the
      decrease in VT carriage post-inoculation. The decrease in VT carriage may be
      conducive to reducing VT transmission within the study area. 

PMID- 24451101
TI  - Epidemiology of extended-spectrum beta-lactamase, AmpC, and carbapenemase
      production in Proteus mirabilis.
AB  - Proteus mirabilis strains that produce extended-spectrum beta-lactamase (ESBL),
      AmpC beta-lactamase, and carbapenemase pose potential threats to patient care
      because most clinical diagnostic laboratories may not attempt to detect these
      three major groups of enzymes. Therefore, the objective of this study was to
      ascertain if P. mirabilis isolates collected from our heathcare facility possess
      various mechanisms of resistance to beta-lactams (i.e., ESBL, AmpC, and
      carbapenemases) and to additionally arrive at conclusions regarding concurrent
      testing for these three mechanism of drug resistance in order to reduce cost and
      time in routine diagnostic testing. Between January 2011 and June 2011, 60
      consecutive non-repeated strains of P. mirabilis were evaluated for production of
      ESBLs, AmpC beta-lactamases, and carbapenemases. Of these, 36 isolates were found
      to be ESBL producers, and 7 (12%) were positive for production of AmpC beta
      lactamases and ESBLs. Therefore, 19.4% of ESBL-producing Proteus strains
      coproduced AmpC enzymes. The modified Hodge test confirmed carbapenemase
      production in only 1 isolate (1.7%), which was also ESBL- and AmpC-positive. The
      clinical impact of additional AmpC expression in ESBL-producing P. mirabilis
      results in a newly acquired resistance to beta-lactamase inhibitors. In addition,
      to save time and costs, we recommend the use of cefepime/cefepime-clavulanate or
      boronic acid for the ESBL detection but in only those strains that were positive
      for ESBL by screening and negative by confirmatory tests. 

PMID- 24451102
TI  - PCR detection of Anaplasma phagocytophilum and Borrelia burgdorferi in Ixodes
      persulcatus ticks in Mongolia.
AB  - A molecular epidemiological survey was conducted to identify the tick-borne
      disease agents Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in
      Selenge Province, Mongolia. The survey was in response to a suspected A.
      phagocytophilum infection in a patient. In 2012, a total of 129 questing Ixodes
      persulcatus adult ticks were sampled by flagging vegetation. A. phagocytophilum
      and Borrelia spp. were detected by PCR, targeting the 16S rDNA (rrs) and 5S-23S
      intergenic spacer region, respectively. Infection rates for A. phagocytophilum
      and B. burgdorferi sensu lato spp. were 6.2% and 55.0%, respectively. Six of the
      129 ticks (4.9%) were coinfected with A. phagocytophilum and B. burgdorferi sensu
      lato. Among Borrelia spp., the highest prevalence rate was that for B. garinii
      20047 type (26.3%), followed by B. afzelii (7.8%) and B. garinii NT29 type
      (7.0%). Furthermore, ticks were detected that were dually infected with B.
      afzelii and B. garinii 20047 type (7.8%) and B. garinii NT29 and 20047 types
      (6.2%). 

PMID- 24451103
TI  - Characteristics of central nervous system tuberculosis in a low-incidence
      country: a series of 20 cases and a review of the literature.
AB  - Central nervous system tuberculosis (CNS-TB) is a devastating manifestation of
      tuberculosis (TB) caused by the hematogenous spread of Mycobacterium
      tuberculosis. Here, I present a retrospective analysis of 20 CNS-TB cases in
      Israel, a country with a low incidence of TB over an 11-year period (2000-2010).
      Most of the cases were those of African migrants, with an increased prevalence in
      adult females and in those with HIV coinfections. Clinical manifestations were
      usually non-specific, and miliary infiltrates were rare. Lymphocytic meningitis
      was frequent with bacteriological confirmation in 50% of the cases. The yields of
      cerebrospinal fluid smear examinations were low (20%). Brain computed tomography
      revealed tuberculomas (45%) and hydrocephalus (15%). All patients received
      individual treatment on the basis of drug susceptibility patterns and adjunctive
      steroid therapy. However, 35% of the patients died within the first year and the
      mortality rate was strongly correlated to disease severity (90%), HIV coinfection
      (85%), and hydrocephalus (66%). Progress in new diagnostic tests and early
      treatment may improve the current high mortality and morbidity rates. 

PMID- 24451104
TI  - Antimicrobial resistance in Salmonella strains clinically isolated in Hyogo,
      Japan (2009-2012).
AB  - The purpose of this study was to examine the in vitro susceptibilities to
      antimicrobial agents and genetic diversity of 195 clinical strains of Salmonella
      spp., which were isolated and examined for the extended-spectrum beta-lactamase
      (ESBL) blaCTX-M gene and the presence of gyrA, gyrB, parC, and parE genes
      mutations in Hyogo, Japan, from 2009 to 2012. Forty-three of the 195 strains were
      antimicrobial resistant. Two Salmonella enterica subsp. enterica strains, 1
      serovar Schwarzengrund, and 1 serovar Enteritidis were identified as ESBL
      producing strains possessing blaCTX-M-15 and blaCTX-M-2, respectively. Among 8
      nalidixic acid-resistant strains, 7 had mutations in gyrA alone or in gyrA and
      parC. In conclusion, we identified CTX-M ESBL-producing Salmonella clinical
      strains with multidrug resistance. Further studies are needed to monitor these
      serious drug-resistant Salmonella strains in Japan. 

PMID- 24451105
TI  - Genetic environments of the transferable plasmid-mediated blaCTX-M-3 gene in
      Serratia marcescens isolates.
AB  - In this study, genetic environments of the transferable plasmid-mediated blaCTX-M
      3 gene were characterized among 14 isolates of cefotaxime-resistant Serratia
      marcescens using PCR and BLAST DNA sequence analysis. A total of 3 types of
      genetic architectures in the regions surrounding this blaCTX-M-3 gene were
      identified. Type I architecture was characterized by the presence of a complete
      insertion sequence of tnpA-ISEcp1, identified as interrupting a reverse IS26
      sequence in the upstream region of the blaCTX-M-3 gene. A reverse-directional
      orf477 fragment was located downstream of the blaCTX-M-3 gene, which was in the
      same direction of the mucA gene. A common region containing the orf513 element
      was located upstream of the mucA gene. Moreover, a copy of the 3'-CS2 element was
      located immediately upstream of the orf513 element. A novel complex class 1
      integron was characterized by the presence of the dfrA19 gene, which was flanked
      by two copies of class 1 integrons. This is the first report to describe the
      dfrA19 gene within a novel complex class 1 integron in S. marcescens isolates
      from Taiwan. This novel complex class 1 integron structure was located distantly
      upstream of the blaCTX-M-3 gene. 

PMID- 24451106
TI  - MePIC, metagenomic pathogen identification for clinical specimens.
AB  - Next-generation DNA sequencing technologies have led to a new method of
      identifying the causative agents of infectious diseases. The analysis comprises
      three steps. First, DNA/RNA is extracted and extensively sequenced from a
      specimen that includes the pathogen, human tissue and commensal microorganisms.
      Second, the sequenced reads are matched with a database of known sequences, and
      the organisms from which the individual reads were derived are inferred. Last,
      the percentages of the organisms' genomic sequences in the specimen (i.e., the
      metagenome) are estimated, and the pathogen is identified. The first and last
      steps have become easy due to the development of benchtop sequencers and
      metagenomic software. To facilitate the middle step, which requires computational
      resources and skill, we developed a cloud-computing pipeline, MePIC: "Metagenomic
      Pathogen Identification for Clinical specimens." In the pipeline, unnecessary
      bases are trimmed off the reads, and human reads are removed. For the remaining
      reads, similar sequences are searched in the database of known nucleotide
      sequences. The search is drastically sped up by using a cloud-computing system.
      The webpage interface can be used easily by clinicians and epidemiologists. We
      believe that the use of the MePIC pipeline will promote metagenomic pathogen
      identification and improve the understanding of infectious diseases. 

PMID- 24451107
TI  - Evaluation of a double-disk synergy test with a common metallo-beta-lactamase
      inhibitor, mercaptoacetate, for detecting NDM-1-producing Enterobacteriaceae and
      Acinetobacter baumannii.

PMID- 24451108
TI  - Foodborne outbreak associated with Escherichia coli O112ac:H19 in China.

PMID- 24451110
TI  - Primary care approaches to musculoskeletal multiple-site joint pain
      pharmacological therapy: a survey of general practitioners.
AB  - Chronic multiple-site joint pain (MSJP) due to osteoarthritis and soft tissue
      disorders is common in people over 50 years old and associated with poor
      outcomes. This study examined current pharmacological approaches to MSJP
      management in primary care. One hundred and fifty general practitioners (GPs)
      attending an educational seminar participated in an electronic survey (mean
      response rate 96%). Most GPs reported treating multiple painful joints
      concurrently (78%) compared with focusing on a single joint (21%). The majority
      believed there was no difference in analgesia for different disorders when
      selecting paracetamol (84%), non-steroidal anti-inflammatory drugs (NSAID)/COX-2
      inhibitors (57%) or opioids (70%). When optimising therapy, intra-class
      optimisation (increase NSAID dose 41%, change to another NSAID/COX-2 inhibitor
      30%) was preferred to inter-class step up therapy (add opioid 23%, change to
      opioid 6%). For NSAID gastrointestinal intolerance, the preference was to add a
      gastro-protective agent (74%). There is a need to better characterise MSJP and
      examine optimal pharmacotherapy regimens. 

PMID- 24451109
TI  - Role of the androgen receptor in breast cancer and preclinical analysis of
      enzalutamide.
AB  - INTRODUCTION: The androgen receptor (AR) is widely expressed in breast cancers
      and has been proposed as a therapeutic target in estrogen receptor alpha (ER)
      negative breast cancers that retain AR. However, controversy exists regarding the
      role of AR, particularly in ER + tumors. Enzalutamide, an AR inhibitor that
      impairs nuclear localization of AR, was used to elucidate the role of AR in
      preclinical models of ER positive and negative breast cancer. METHODS: We
      examined nuclear AR to ER protein ratios in primary breast cancers in relation to
      response to endocrine therapy. The effects of AR inhibition with enzalutamide
      were examined in vitro and in preclinical models of ER positive and negative
      breast cancer that express AR. RESULTS: In a cohort of 192 women with ER + breast
      cancers, a high ratio of AR:ER (>=2.0) indicated an over four fold increased risk
      for failure while on tamoxifen (HR = 4.43). The AR:ER ratio had an independent
      effect on risk for failure above ER % staining alone. AR:ER ratio is also an
      independent predictor of disease-free survival (HR = 4.04, 95% CI: 1.68, 9.69; p
      = 0.002) and disease specific survival (HR = 2.75, 95% CI: 1.11, 6.86; p = 0.03).
      Both enzalutamide and bicalutamide inhibited 5-alpha-dihydrotestosterone (DHT)
      mediated proliferation of breast cancer lines in vitro; however, enzalutamide
      uniquely inhibited estradiol (E2)-mediated proliferation of ER+/AR + breast
      cancer cells. In MCF7 xenografts (ER+/AR+) enzalutamide inhibited E2-driven tumor
      growth as effectively as tamoxifen by decreasing proliferation. Enzalutamide also
      inhibited DHT- driven tumor growth in both ER positive (MCF7) and negative (MDA
      MB-453) xenografts, but did so by increasing apoptosis. CONCLUSIONS: AR to ER
      ratio may influence breast cancer response to traditional endocrine therapy.
      Enzalutamide elicits different effects on E2-mediated breast cancer cell
      proliferation than bicalutamide. This preclinical study supports the initiation
      of clinical studies evaluating enzalutamide for treatment of AR+ tumors
      regardless of ER status, since it blocks both androgen- and estrogen- mediated
      tumor growth.

PMID- 24451111
TI  - Younger patients are at increased risk for graft rupture and contralateral injury
      after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Graft rupture of the same knee or injury to the anterior cruciate
      ligament (ACL) in the contralateral knee is a devastating outcome after ACL
      reconstruction surgery. While a number of factors have been identified as
      potentially increasing the risk of subsequent ACL injury, the literature is far
      from definitive. PURPOSE: To determine the rates of graft rupture and
      contralateral ACL injury in a large cohort and to investigate patient
      characteristics that may be associated with these. STUDY DESIGN: Case-control
      study; Level of evidence, 3. METHODS: A consecutive cohort of 750 patients who
      had undergone primary ACL reconstruction surgery with a minimum 3-year follow-up
      were questioned about the incidence of ACL graft rupture, contralateral ACL
      injury, family history of ACL injury, and current activity level. Patient
      databases provided details for age, sex, original injury mechanism, meniscus or
      articular surface injury, and graft diameter. RESULTS: Responses were received
      from 561 patients (75%) at a mean +/- SD follow-up time of 4.8 +/- 1.1 years.
      Anterior cruciate ligament graft ruptures occurred in 25 patients (4.5%), and
      contralateral ACL injuries occurred in 42 patients (7.5%). The highest incidence
      of further ACL injury occurred in patients younger than 20 years at the time of
      surgery. In this group, 29% sustained a subsequent ACL injury to either knee. The
      odds for sustaining an ACL graft rupture or contralateral injury increased 6- and
      3-fold, respectively, for patients younger than 20 years. Returning to
      cutting/pivoting sports increased the odds of graft rupture by a factor of 3.9
      and contralateral rupture by a factor of 5. A positive family history doubled the
      odds for both graft rupture and contralateral ACL injury. CONCLUSION: Patients
      younger than 20 years who undergo ACL reconstruction are at significantly
      increased risk for both graft rupture and contralateral ACL injury. Whether age
      per se is a risk factor or age represents a proxy for other factors remains to be
      determined.

PMID- 24451112
TI  - Application of tendon-derived stem cell sheet for the promotion of graft healing
      in anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Both osteointegration and remodeling of graft midsubstance
      (collectively called graft healing) are slow processes after anterior cruciate
      ligament (ACL) reconstruction. Tendon-derived stem cells (TDSCs) form a cell
      sheet after treatment with connective tissue growth factor (CTGF) and ascorbic
      acid, which exhibits higher tenogenic and maintains high chondro-osteogenic gene
      expression of TDSCs. No external scaffold is required for cell delivery.
      HYPOTHESIS: Wrapping the TDSC sheet around the ACL graft would promote early
      graft healing in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS:
      Green fluorescent protein (GFP) rat TDSCs were treated with connective tissue
      growth factor and ascorbic acid to promote cell sheet formation. Rats undergoing
      unilateral ACL reconstruction were divided into a control group and a TDSC group.
      The tendon graft was wrapped with the GFP-TDSC sheet before graft insertion in
      the TDSC group. At weeks 2, 6, and 12 after reconstruction, the samples were
      harvested for computed tomography imaging and histologic or biomechanical
      testing. The fate of the transplanted cell sheet was examined by
      immunohistochemical staining of GFP. RESULTS: There were significantly higher
      tunnel bone mineral density (BMD) (42.3% increase, P = .047) and bone
      volume/total volume (BV/TV) (625% increase, P = .009) at the metaphyseal region
      of the tibial tunnel at week 2 and at the femoral tunnel at week 6 (BMD: 30.8%
      increase, P = .014; BV/TV: 100% increase, P = .014) in the TDSC group compared
      with the control group. Only the TDSC group showed a time-dependent increase in
      tunnel BMD (overall P = .038) and BV/TV (overall P = .015) at the epiphyseal
      region of the tibial tunnel. Semiquantitative image analysis showed better graft
      osteointegration and higher intra-articular graft integrity with lower
      cellularity and vascularity, better cell alignment, and higher collagen
      birefringence in the TDSC group. The ultimate load at week 2 (52.5% increase, P =
      .027) and stiffness at week 6 (62% increase, P = .008) were significantly higher
      in the TDSC group. Cells positive for GFP were observed in all samples in the
      TDSC group at week 2 but became reduced with time after reconstruction.
      CONCLUSION: The TDSC sheet improved early graft healing after ACL reconstruction
      in the rat model. CLINICAL RELEVANCE: The TDSC sheet could potentially be used
      for the promotion of graft healing in ACL reconstruction.

PMID- 24451113
TI  - Anatomic variance of the iliopsoas tendon.
AB  - BACKGROUND: The iliopsoas tendon has been implicated as a generator of hip pain
      and a cause of labral injury due to impingement. Arthroscopic release of the
      iliopsoas tendon has become a preferred treatment for internal snapping hips.
      Traditionally, the iliopsoas tendon has been considered the conjoint tendon of
      the psoas major and iliacus muscles, although anatomic variance has been
      reported. HYPOTHESIS: The iliopsoas tendon consists of 2 discrete tendons in the
      majority of cases, arising from both the psoas major and iliacus muscles. STUDY
      DESIGN: Descriptive laboratory study. METHODS: Fifty-three nonmatched, fresh
      frozen, cadaveric hemipelvis specimens (average age, 62 years; range, 47-70
      years; 29 male and 24 female) were used in this study. The iliopsoas muscle was
      exposed via a Smith-Petersen approach. A transverse incision across the entire
      iliopsoas musculotendinous unit was made at the level of the hip joint. Each
      distinctly identifiable tendon was recorded, and the distance from the lesser
      trochanter was recorded. RESULTS: The prevalence of a single-, double-, and
      triple-banded iliopsoas tendon was 28.3%, 64.2%, and 7.5%, respectively. The
      psoas major tendon was consistently the most medial tendinous structure, and the
      primary iliacus tendon was found immediately lateral to the psoas major tendon
      within the belly of the iliacus muscle. When present, an accessory iliacus tendon
      was located adjacent to the primary iliacus tendon, lateral to the primary
      iliacus tendon. CONCLUSION: Once considered a rare anatomic variant, the finding
      of >=2 distinct tendinous components to the iliacus and psoas major muscle groups
      is an important discovery. It is essential to be cognizant of the possibility
      that more than 1 tendon may exist to ensure complete release during endoscopy.
      CLINICAL SIGNIFICANCE: Arthroscopic release of the iliopsoas tendon is a well
      accepted surgical treatment for iliopsoas impingement. The most widely used site
      for tendon release is at the level of the anterior hip joint. The findings of
      this novel cadaveric anatomy study suggest that surgeons should be mindful that
      more than 1 tendon may be present and require release for curative treatment.

PMID- 24451114
TI  - TRAIL-secreting mesenchymal stem cells promote apoptosis in heat-shock-treated
      liver cancer cells and inhibit tumor growth in nude mice.
AB  - Liver cancer is one of the top six leading causes of cancer-related death.
      Radiofrequency ablation (RFA) is an important means of treating liver cancer.
      Residual cancer after RFA is the most frequent cause of recurrence in cases of
      liver cancer. The main difference between residual cancer cells and ordinary
      liver cancer cells is that residual cancer cells experience heat shock. The
      secretable form of trimeric human tumor necrosis factor-related apoptosis
      inducing ligand (stTRAIL) induces apoptosis in a variety of human cancers but not
      in normal tissues. It has shown potent cancer-selective killing activity and has
      drawn considerable attention as a possible cancer therapy. In the present work,
      the therapeutic potential of this stTRAIL-based gene therapy was evaluated in
      hepatocellular carcinoma subjected to RFA. Rat bone marrow mesenchymal stem cells
      (BM-MSCs) were isolated and transduced with a lentiviral vector encoding stTRAIL
      (stTRAIL-MSCs, T-MSCs). Cells treated with heat treatment at 43  degrees C for 45
      min served as simulated residual cancer cells. After treatment with T-MSCs,
      apoptosis in heat-shock-treated liver cancer cells increased significantly, and
      caspase-3 was upregulated. When T-MSCs were subcutaneously injected into nude
      mice, they localized to the tumors and inhibited tumor growth, significantly
      increasing survival. Collectively, the results of the present study indicate that
      BM-MSC can provide a steady source of stTRAIL and may be suitable for use in the
      prevention of the recurrence of hepatocellular carcinoma after RFA with
      secretable trimeric TRAIL. 

PMID- 24451115
TI  - Restoring ciliary function to differentiated primary ciliary dyskinesia cells
      with a lentiviral vector.
AB  - Primary ciliary dyskinesia (PCD) is a genetically heterogenous autosomal
      recessive disease in which mutations disrupt ciliary function, leading to
      impaired mucociliary clearance and life-long lung disease. Mouse tracheal cells
      with a targeted deletion in the axonemal dynein intermediate chain 1 (Dnaic1)
      gene differentiate normally in culture but lack ciliary activity. Gene transfer
      to undifferentiated cultures of mouse Dnaic1(-/-) cells with a lentiviral vector
      pseudotyped with avian influenza hemagglutinin restored Dnaic1 expression and
      ciliary activity. Importantly, apical treatment of well-differentiated cultures
      of mouse Dnaic1(-/-) cells with lentiviral vector also restored ciliary activity,
      demonstrating successful gene transfer from the apical surface. Treatment of
      Dnaic1(flox/flox) mice expressing an estrogen-responsive Cre recombinase with
      different doses of tamoxifen indicated that restoration of ~20% of ciliary
      activity may be sufficient to prevent the development of rhinosinusitis. However,
      although administration of a beta-galactosidase-expressing vector into control
      mice demonstrated efficient gene transfer to the nasal epithelium, treatment of
      Dnaic1(-/-) mice resulted in a low level of gene transfer, demonstrating that the
      severe rhinitis present in these animals impedes gene transfer. The results
      demonstrate that gene replacement therapy may be a viable treatment option for
      PCD, but further improvements in the efficiency of gene transfer are necessary. 

PMID- 24451116
TI  - Salmonella induce autophagy in melanoma by the downregulation of AKT/mTOR
      pathway.
AB  - Salmonella have been demonstrated to inhibit tumor growth. However, the mechanism
      of Salmonella-induced tumor cell death is less defined. Autophagy is a cellular
      process that mediates the degradation of long-lived proteins and unwanted
      organelles in the cytosol. Tumor cells frequently display lower levels of basal
      autophagic activity than their normal counterparts and fail to increase
      autophagic activity in response to stresses. Autophagy is involved in the cell
      defense elimination of bacteria. The signaling pathways leading to activation of
      Salmonella-induced autophagy in tumor cells remain to be elucidated. We used
      autophagy inhibitor (3-Methyladenine) and apoptosis inhibitor (Z-VAD-FMK) to
      demonstrate that Salmonella may induce cell death via apoptosis and autophagic
      pathway. Meanwhile, we suggested that Salmonella induce autophagy in a dose- and
      time-dependent manner. The autophagic markers were increased after tumor cell
      infected with Salmonella. In addition, the protein express levels of phosph
      protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), phosph
      p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased by western
      analysis after Salmonella infection. In conclusion, our results point out that
      Salmonella induce the autophagic signaling pathway via downregulation of AKT/mTOR
      pathway. Herein, our findings that Salmonella in controlling tumor growth may
      induce autophagic signal pathway. 

PMID- 24451117
TI  - Immune escape from NY-ESO-1-specific T-cell therapy via loss of heterozygosity in
      the MHC.
AB  - Adoptive immunotherapy of tumors with T cells specific for the cancer-testis
      antigen NY-ESO-1 has shown great promise in preclinical models and in early stage
      clinical trials. Tumor persistence or recurrence after NY-ESO-1-specific therapy
      occurs, however, and the mechanisms of recurrence remain poorly defined. In a
      murine xenograft model of NY-ESO-1(+) multiple myeloma, we observed tumor
      recurrence after adoptive transfer of CD8(+) T cells genetically redirected to
      the prototypic NY-ESO-1157-165 peptide presented by HLA-A*02:01. Analysis of the
      myeloma cells that had escaped from T-cell control revealed intact expression of
      NY-ESO-1 and B2M, but selective, complete loss of HLA-A*02:01 expression from the
      cell surface. Loss of heterozygosity (LOH) in the major histocompatibility
      complex (MHC) involving the HLA-A locus was identified in the tumor cells, and
      further analysis revealed selective loss of the allele encoding HLA-A*02:01.
      Although LOH involving the MHC has not been described in myeloma patients with
      persistent or recurrent disease after immune therapies such as allogeneic
      hematopoietic cell transplantation (HCT), it has been described in patients with
      acute myelogenous leukemia who relapsed after allogeneic HCT. These results
      suggest that MHC loss should be evaluated in patients with myeloma and other
      cancers who relapse after adoptive NY-ESO-1-specific T-cell therapy. 

PMID- 24451118
TI  - HSV-mediated p55TNFSR reduces neuropathic pain induced by HIV gp120 in rats
      through CXCR4 activity.
AB  - Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating
      chronic condition that is severe and unrelenting. Despite extensive research, the
      detailed neuropathological mechanisms remain unknown, which hinders our ability
      to develop effective treatments. In this study, we investigated the role of
      proinflammatory molecules, tumor necrosis factor-alpha (TNFalpha), CXCR4 and
      stromal-derived factor-1 alpha (SDF1alpha), in the L4/5 dorsal root ganglia (DRG)
      and the spinal dorsal horn in HIV gp120 protein-mediated neuropathic pain. Our
      results showed that the application of HIV gp120 to the sciatic nerve induced
      upregulation of TNFalpha, CXCR4 and SDF1alpha in both the DRG and the lumbar
      spinal dorsal horn. Non-replicating herpes simplex virus (HSV) vector encoding
      the p55TNFSR gene and producing a TNF-soluble receptor (TNFSR) to block
      bioactivity of TNFalpha reversed mechanical allodynia. Intrathecal AMD3100 (CXCR4
      antagonist) increased mechanical threshold. The HSV vectors expressing p55TNFSR
      reversed upregulation of TNFalpha, CXCR4 and SDF1alpha induced by gp120 in the
      DRG and the spinal dorsal horn. These studies suggest that proinflammatory
      TNFalpha to the CXCR4/SDF1 pathway has an important role in the HIV-related
      neuropathic pain state and that blocking the proinflammatory cytokines or
      chemokines is able to reduce neuropathic pain. This work provides a novel gene
      therapy proof-of-concept for HIV-associated neuropathic pain. 

PMID- 24451119
TI  - Comparative cost-effectiveness models for the treatment of multiple myeloma.
AB  - OBJECTIVES: To compare cost effectiveness models for the first-line treatment of
      multiple myeloma, and explore the differences between the models' structure,
      parameters, assumptions and results. METHODS: Three cost effectiveness models for
      the treatment of multiple myeloma, were compared that had been developed to
      inform resource allocation in the UK for the chemotherapy regimens bortezomib,
      melphalan and prednisolone (BMP); and melphalan, prednisolone and thalidomide
      (MPT) versus melphalan and prednisolone (MP). The models used alternative
      approaches and assumptions to estimate the overall survival and progression-free
      survival for each of the interventions. Through the use of sensitivity analyses,
      the most influential parameters and assumptions of each of the models were
      identified. RESULTS: The models developed by the manufacturers gave conflicting
      results, with each manufacturer favouring their drug. The differences between the
      model results were determined by two parameters: the hazard ratio for overall
      survival for MPT vs. MP and the cost of bortezomib. CONCLUSIONS: Using models
      developed for assessing treatments for multiple myeloma we demonstrated that it
      was feasible to compare models, which then aided decision makers in making
      reimbursement decisions.

PMID- 24451120
TI  - The harm of intraoperative awareness.

PMID- 24451121
TI  - Homebirth and the future child.
AB  - Debate around homebirth typically focuses on the risk of maternal and perinatal
      mortality and morbidity--the primary focus is on deaths. There is little
      discussion on the risk of long-term disability to the future child. We argue that
      maternal and perinatal mortality are truly tragic outcomes, but focusing
      disproportionately on them overshadows the importance of harm to a future child
      created by avoidable, foreseeable disability. The interests of future children
      are of great moral importance. Both professionals and pregnant women have an
      ethical obligation to minimize risk of long-term harm to the future child; harm
      to people who will exist is a clear and uncontroversial morally relevant harm.
      The medical literature does not currently adequately address the risk of long
      term disability, which is at least as relevant as other outcomes. The choice of
      place of elective birth (home, hospital or other) may only be justified if it
      does not expose the future child to an unreasonable increased risk of avoidable
      disability. Doctors' duty of care for the life of the pregnant woman and her
      fetus may be overridden by the woman's choices. But further research is required
      to document the prevalence of long term avoidable disability associated with
      different birth place choices. Couples should be informed of this risk and
      doctors should attempt to dissuade couples when they elect a place of birth that
      puts the health and well-being of the future child at risk.

PMID- 24451122
TI  - A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for
      HCV genotype 1 infection.
AB  - BACKGROUND: Daclatasvir-containing regimens have the potential to address
      limitations of current regimens combining peginterferon alfa and ribavirin with
      first-generation protease inhibitors for treatment of chronic HCV genotype 1
      infection. METHODS: In this randomized, double-blind study, 27 Japanese treatment
      naive patients received once-daily daclatasvir 10 mg or 60 mg or placebo, each
      combined with peginterferon alfa-2b/ribavirin; 18 prior null (n=9) or partial
      (n=9) responders received the same daclatasvir-containing regimens without a
      placebo arm. Daclatasvir recipients with protocol-defined response (HCV RNA<15
      IU/ml at week 4, undetectable at week 12) were treated for 24 weeks; those
      without protocol-defined response and placebo recipients continued treatment to
      week 48. RESULTS: Sustained virological response 24 weeks post-treatment (SVR24)
      was achieved by 66.7%, 90.0% and 62.5% of treatment-naive patients in the
      daclatasvir 10 mg, 60 mg and placebo groups, respectively. Prior non-responders
      had more frequent virological failure; 22.2% and 33.3% of daclatasvir 10 mg and
      60 mg recipients, respectively, achieved SVR24. Adverse events were similar
      across groups and were typical of peginterferon alfa-2b/ribavirin. Pyrexia,
      headache, alopecia, decreased appetite and malaise were the most common adverse
      events; two daclatasvir recipients discontinued due to adverse events.
      CONCLUSIONS: Daclatasvir 60 mg combined with peginterferon alfa-2b and ribavirin
      achieved a high rate of SVR24 in treatment-naive patients with HCV genotype 1
      infection, with tolerability similar to that of peginterferon alfa-2b/ribavirin
      alone. However, regimens with greater antiviral potency are needed for prior non
      responders.

PMID- 24451123
TI  - Unique microbial communities persist in individual cystic fibrosis patients
      throughout a clinical exacerbation.
AB  - BACKGROUND: Cystic fibrosis (CF) is caused by inherited mutations in the cystic
      fibrosis transmembrane conductance regulator gene and results in a lung
      environment that is highly conducive to polymicrobial infection. Over a lifetime,
      decreasing bacterial diversity and the presence of Pseudomonas aeruginosa in the
      lung are correlated with worsening lung disease. However, to date, no change in
      community diversity, overall microbial load or individual microbes has been shown
      to correlate with the onset of an acute exacerbation in CF patients. We followed
      17 adult CF patients throughout the course of clinical exacerbation, treatment
      and recovery, using deep sequencing and quantitative PCR to characterize
      spontaneously expectorated sputum samples RESULTS: We identified approximately
      170 bacterial genera, 12 of which accounted for over 90% of the total bacterial
      load across all patient samples. Genera abundant in any single patient sample
      tended to be detectable in most samples. We found that clinical stages could not
      be distinguished by absolute Pseudomonas aeruginosa load, absolute total
      bacterial load or the relative abundance of any individual genus detected, or
      community diversity. Instead, we found that the microbial structure of each
      patient's sputum microbiome was distinct and resilient to exacerbation and
      antibiotic treatment. CONCLUSION: Consistent with previously reported sputum
      microbiome studies we found that total and relative abundance of genera at the
      population level were remarkably stable for individual patients regardless of
      clinical status. Patient-by-patient analysis of diversity and relative abundance
      of each individual genus revealed a complex microbial landscape and highlighted
      the difficulty of identifying a universal microbial signature of exacerbation.
      Overall, at the genus level, we find no evidence of a microbial signature of
      clinical stage.

PMID- 24451124
TI  - Effect and mechanism of Mitomycin C combined with recombinant adeno-associated
      virus type II against glioma.
AB  - The effect of chemotherapy drug Mitomycin C (MMC) in combination with recombinant
      adeno-associated virus II (rAAV2) in cancer therapy was investigated, and the
      mechanism of MMC affecting rAAV2's bioactivity was also studied. The combination
      effect was evaluated by the level of GFP and TNF expression in a human glioma
      cell line, and the mechanism of MMC effects on rAAV mediated gene expression was
      investigated by AAV transduction related signal molecules. C57 and BALB/c nude
      mice were injected with rAAV-EGFP or rAAV-TNF alone, or mixed with MMC, to
      evaluate the effect of MMC on AAV-mediated gene expression and tumor suppression.
      MMC was shown to improve the infection activity of rAAV2 both in vitro and in
      vivo. Enhancement was found to be independent of initial rAAV2 receptor binding
      stage or subsequent second-strand synthesis of target DNA, but was related to
      cell cycle retardation followed by blocked genome degradation. In vivo injection
      of MMC combined with rAAV2 into the tumors of the animals resulted in significant
      suppression of tumor growth. It was thus demonstrated for the first time that MMC
      could enhance the expression level of the target gene mediated by rAAV2. The
      combination of rAAV2 and MMC may be a promising strategy in cancer therapy.

PMID- 24451125
TI  - Heat-killed VSL#3 ameliorates dextran sulfate sodium (DSS)-induced acute
      experimental colitis in rats.
AB  - To determine the effects of heat-killed VSL#3 (B. breve, B. longum and B.
      infantis; L. plantarum, L. bulgaricus, L. casei and L. acidophilus; S. salivarius
      subsp. thermophilus) therapy in the dextran sulfate sodium (DSS)-induced acute
      experimental colitis in rats. Acute experimental colitis was induced in rats by
      5% DSS and freely drink for seven days. Beginning on Day 8, rats underwent gavage
      once daily for seven days with heat-killed probiotic VSL#3 (0.6 g/kg/day),
      colonic damage was evaluated histologically and biochemically seven days after
      gavage. Expression of inflammatory related mediators (STAT3, P-STAT3) and
      cytokines (IL-6, IL-23, TGFbeta) in colonic tissue were detected. The results
      revealed that heat-killed and live VSL#3 have identical anti-inflammatory
      properties by the assessed DAI (disease activity index), colon length,
      histological tissue and MPO activity. Heat-killed and live VSL#3 results in
      reduced IL-6, IL-23, TGFbeta, STAT3 and P-STAT3 expression in colonic tissue.
      Heat-killed and live VSL#3 have showed the similar anti-inflammatory activity by
      inhibiting IL-6/STAT3 pathway in the DSS-induced acute experimental colitis in
      rats.

PMID- 24451126
TI  - Molecular dynamics simulation of the crystallizable fragment of IgG1-insights for
      the design of Fcabs.
AB  - An interesting format in the development of therapeutic monoclonal antibodies
      uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its
      structural loops allows generation of an antigen binding site. However, this
      might impair the molecule's conformational stability, which can be overcome by
      introducing stabilizing point mutations in the CH3 domains. These point mutations
      often affect the stability and unfolding behavior of both the CH2 and CH3
      domains. In order to understand this cross-talk, molecular dynamics simulations
      of the domains of the Fc fragment of human IgG1 are reported. The structure of
      human IgG1-Fc obtained from X-ray crystallography is used as a starting point for
      simulations of the wild-type protein at two different pH values. The stabilizing
      effect of a single point mutation in the CH3 domain as well as the impact of the
      hinge region and the glycan tree structure connected to the CH2 domains is
      investigated. Regions of high local flexibility were identified as potential
      sites for engineering antigen binding sites. Obtained data are discussed with
      respect to the available X-ray structure of IgG1-Fc, directed evolution
      approaches that screen for stability and use of the scaffold IgG1-Fc in the
      design of antigen binding Fc proteins. 

PMID- 24451127
TI  - Pharmacokinetic comparison of berberine in rat plasma after oral administration
      of berberine hydrochloride in normal and post inflammation irritable bowel
      syndrome rats.
AB  - In the present study, post inflammation irritable bowel syndrome (PI-IBS) rats
      were firstly established by intracolonic instillation of acetic acid with
      restraint stress. Then the pharmacokinetics of berberine in the rat plasma were
      compared after oral administration of berberine hydrochloride (25 mg/kg) to
      normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was
      achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were
      collected at 15 different points in time and the pharmacokinetic parameters were
      analyzed by WinNonlin software. Compared with the normal group, area under the
      plasma concentration vs. time curve from zero to last sampling time (AUC0-t) and
      total body clearance (CL/F) in the model group significantly increased or
      decreased, (2039.49 +/- 492.24 vs. 2763.43 +/- 203.14; 4999.34 +/- 1198.79 vs.
      3270.57 +/- 58.32) respectively. The results indicated that the pharmacokinetic
      process of berberine could be altered in PI-IBS pathological conditions. 

PMID- 24451128
TI  - 1-(2,6-dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone-induced cell cycle
      arrest in G1/G0 in HT-29 cells human colon adenocarcinoma cells.
AB  - 1-(2,6-Dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone (DMHE) was
      isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff.) Boerl
      fruits and the structure confirmed by GC-MS (gas chromatography-mass
      spectrometry) and NMR (nuclear magnetic resonance) analysis. This compound was
      tested on the HT-29 human colon adenocarcinoma cell line using MTT (method of
      transcriptional and translational) cell proliferation assay. The results of MTT
      assay showed that DMHE exhibited good cytotoxic effect on HT-29 cells in a dose-
      and time-dependent manner but no cytotoxic effect on the MRC-5 cell line after 72
      h incubation. Morphological features of apoptotic cells upon treatment by DMHE,
      e.g., cell shrinkage and membrane blebbing, were examined by an inverted and
      phase microscope. Other features, such as chromatin condension and nuclear
      fragmentation were studied using acridine orange and propidium iodide staining
      under the fluorescence microscope. Future evidence of apoptosis/necrosis was
      provided by result fromannexin V-FITC/PI (fluorescein-isothiocyanate/propidium
      iodide) staining revealed the percentage of early apoptotic, late apoptotic,
      necrotic and live cells in a dose- and time-dependent manner using flow
      cytometry. Cell cycle analysis showed G0/G1 arrest in a time-dependent manner. A
      western blot analysis indicated that cell death might be associated with the up
      regulation of the pro-apoptotic proteins Bax PUMA. However, the anit-apotptic
      proteins Bcl-2, Bcl-xL, and Mcl-1 were also found to increase in a time-dependent
      manner. The expression of the pro-apoptotic protein Bak was not observed. 

PMID- 24451129
TI  - The inhibitory effect of quercetin on asymmetric dimethylarginine-induced
      apoptosis is mediated by the endoplasmic reticulum stress pathway in glomerular
      endothelial cells.
AB  - Asymmetric dimethylarginine (ADMA) is considered an independent mortality and
      cardiovascular risk factor in chronic kidney disease (CKD) patients, and
      contributes to the development of renal fibrosis. Quercetin (QC), a natural
      component of foods, protects against renal injury. Here, we explored the possible
      mechanisms that are responsible for ADMA-induced renal fibrosis and the
      protective effect of QC. We found that ADMA treatment activated the endoplasmic
      reticulum (ER) stress sensor proteins phosphorylated protein kinase RNA-activated
      like ER kinase (PERK) and inositol requiring-1alpha (IRE1), which correspondingly
      induced C/EBP homologous protein (CHOP) expression and phosphorylated c-Jun N
      terminal kinase (JNK) phosphorylation in glomerular endothelial cells (GEnCs).
      Following this, ADMA promoted ER stress-induced apoptosis and resulted in
      transforming growth factor beta (TGF-beta) expression in GEnCs. SP600125, an
      inhibitor of JNK, and CHOP siRNA protected against ADMA-induced cell apoptosis
      and TGF-beta expression. QC prevented ADMA-induced PERK and IRE1 apoptotic ER
      stress pathway activation. Also, ADMA-induced GEnCs apoptosis and TGF-beta
      expression was reduced by QC. Overexpression of CHOP blocked QC-mediated
      protection from apoptosis in ER stressed cells. Overall, these observations
      indicate that ADMA may induce GEnCs apoptosis and TGF-beta expression by
      targeting the PERK-CHOP and IRE1-JNK pathway. In addition, drugs such as QC
      targeting ER stress may hold great promise for the development of novel therapies
      against ADMA-induced renal fibrosis.

PMID- 24451130
TI  - Low prostate concentration of lycopene is associated with development of prostate
      cancer in patients with high-grade prostatic intraepithelial neoplasia.
AB  - Prostate cancer (PC) is a frequent male malignancy and represents the second most
      diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade
      prostatic intraepithelial neoplasia (HGPIN), can be detected years before
      progression to PC, early diagnosis and chemoprevention are targeted strategies to
      reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained
      in tomatoes, is a promising candidate for the chemoprevention of PC. However, its
      efficacy in humans remains controversial. The present study aimed to investigate
      the relevance of plasma and prostate concentration of lycopene after a lycopene
      enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed
      with HGPIN were administered a lycopene-enriched diet (20-25 mg/day of lycopene;
      through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month
      follow-up prostate biopsy assessed progression to PC. Patients were classified
      into three groups according to the histopathological features of the 6-month
      follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene
      levels were measured before and after the dietary lycopene supplementation.
      Prostatic lycopene concentration was only assessed after the supplementation
      diet. Only prostatic lycopene concentration showed significant differences
      between the three groups (p = 0.03). Prostatic lycopene concentration below a 1
      ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003).
      We observed no overall benefits from a 6-month lycopene supplementation, as the
      rate of HGPIN progression to PC in our population (9/32, 28%) was similar to
      rates reported in the literature. Baseline PSA levels also showed no significant
      changes after a lycopene-enriched diet. Our findings point to prostatic lycopene
      concentration as a promising biomarker of PC. Further prospective longitudinal
      studies are needed to assess the prognostic role of prostatic lycopene in PC.

PMID- 24451131
TI  - Secondary plant products causing photosensitization in grazing herbivores: their
      structure, activity and regulation.
AB  - Photosensitivity in animals is defined as a severe dermatitis that results from a
      heightened reactivity of skin cells and associated dermal tissues upon their
      exposure to sunlight, following ingestion or contact with UV reactive secondary
      plant products. Photosensitivity occurs in animal cells as a reaction that is
      mediated by a light absorbing molecule, specifically in this case a plant
      produced metabolite that is heterocyclic or polyphenolic. In sensitive animals,
      this reaction is most severe in non-pigmented skin which has the least protection
      from UV or visible light exposure. Photosensitization in a biological system such
      as the epidermis is an oxidative or other chemical change in a molecule in
      response to light-induced excitation of endogenous or exogenously-delivered
      molecules within the tissue. Photo-oxidation can also occur in the plant itself,
      resulting in the generation of reactive oxygen species, free radical damage and
      eventual DNA degradation. Similar cellular changes occur in affected herbivores
      and are associated with an accumulation of photodynamic molecules in the affected
      dermal tissues or circulatory system of the herbivore. Recent advances in our
      ability to identify and detect secondary products at trace levels in the plant
      and surrounding environment, or in organisms that ingest plants, have provided
      additional evidence for the role of secondary metabolites in photosensitization
      of grazing herbivores. This review outlines the role of unique secondary products
      produced by higher plants in the animal photosensitization process, describes
      their chemistry and localization in the plant as well as impacts of the
      environment upon their production, discusses their direct and indirect effects on
      associated animal systems and presents several examples of well-characterized
      plant photosensitization in animal systems. 

PMID- 24451132
TI  - Plant dependence on rhizobia for nitrogen influences induced plant defenses and
      herbivore performance.
AB  - Symbiotic rhizobia induce many changes in legumes that could affect aboveground
      interactions with herbivores. We explored how changing the intensity of
      Bradyrhizobium japonicum, as modulated by soil nitrogen (N) levels, influenced
      the interaction between soybean (Glycine max) and herbivores of different feeding
      guilds. When we employed a range of fertilizer applications to manipulate soil N,
      plants primarily dependent on rhizobia for N exhibited increased root nodulation
      and higher levels of foliar ureides than plants given N fertilizer; yet all
      treatments maintained similar total N levels. Soybean podworm (Helicoverpa zea)
      larvae grew best on plants with the highest levels of rhizobia but, somewhat
      surprisingly, preferred to feed on high-N-fertilized plants when given a choice.
      Induction of the defense signaling compound jasmonic acid (JA) by H. zea feeding
      damage was highest in plants primarily dependent on rhizobia. Differences in
      rhizobial dependency on soybean did not appear to affect interactions with the
      phloem-feeding soybean aphid (Aphis glycines). Overall, our results suggest that
      rhizobia association can affect plant nutritional quality and the induction of
      defense signaling pathways and that these effects may influence herbivore feeding
      preferences and performance-though such effects may vary considerably for
      different classes of herbivores.

PMID- 24451133
TI  - Dopamine D4 receptor counteracts morphine-induced changes in u opioid receptor
      signaling in the striosomes of the rat caudate putamen.
AB  - The mu opioid receptor (MOR) is critical in mediating morphine analgesia.
      However, prolonged exposure to morphine induces adaptive changes in this receptor
      leading to the development of tolerance and addiction. In the present work we
      have studied whether the continuous administration of morphine induces changes in
      MOR protein levels, its pharmacological profile, and MOR-mediated G-protein
      activation in the striosomal compartment of the rat CPu, by using
      immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPgammaS
      autoradiography. MOR immunoreactivity, agonist binding density and its coupling
      to G proteins are up-regulated in the striosomes by continuous morphine treatment
      in the absence of changes in enkephalin and dynorphin mRNA levels. In addition,
      co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077
      fully counteracts these adaptive changes in MOR, in spite of the fact that
      continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same
      degree as seen after continuous morphine treatment. Thus, in spite of the fact
      that both receptors can be coupled to Gi/0 protein, the present results give
      support for the existence of antagonistic functional D4R-MOR receptor-receptor
      interactions in the adaptive changes occurring in MOR of striosomes on continuous
      administration of morphine.

PMID- 24451134
TI  - Genetic deletion of Rheb1 in the brain reduces food intake and causes
      hypoglycemia with altered peripheral metabolism.
AB  - Excessive food/energy intake is linked to obesity and metabolic disorders, such
      as diabetes. The hypothalamus in the brain plays a critical role in the control
      of food intake and peripheral metabolism. The signaling pathways in hypothalamic
      neurons that regulate food intake and peripheral metabolism need to be better
      understood for developing pharmacological interventions to manage eating behavior
      and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is
      a master regulator of cellular metabolism in different cell types.
      Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic
      neurons alter food intake and body weight. Our previous study identified Rheb1
      (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in
      the brain. Here we examine whether central Rheb1 regulates food intake and
      peripheral metabolism through mTORC1 signaling. We find that genetic deletion of
      Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food
      intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid
      mobilization in adipose tissue and ketogenesis in the liver. Our work highlights
      the importance of central Rheb1 signaling in euglycemia and energy homeostasis in
      animals. 

PMID- 24451135
TI  - Temperature-responsive poly(epsilon-caprolactone) cell culture platform with
      dynamically tunable nano-roughness and elasticity for control of myoblast
      morphology.
AB  - We developed a dynamic cell culture platform with dynamically tunable nano
      roughness and elasticity. Temperature-responsive poly(epsilon-caprolactone) (PCL)
      films were successfully prepared by crosslinking linear and tetra-branched PCL
      macromonomers. By optimizing the mixing ratios, the crystal-amorphous transition
      temperature (Tm) of the crosslinked film was adjusted to the biological relevant
      temperature (~33  degrees C). While the crosslinked films are relatively stiff
      (50 MPa) below the Tm, they suddenly become soft (1 MPa) above the Tm.
      Correspondingly, roughness of the surface was decreased from 63.4-12.4 nm. It is
      noted that the surface wettability was independent of temperature. To investigate
      the role of dynamic surface roughness and elasticity on cell adhesion, cells were
      seeded on PCL films at 32  degrees C. Interestingly, spread myoblasts on the film
      became rounded when temperature was suddenly increased to 37  degrees C, while
      significant changes in cell morphology were not observed for fibroblasts. These
      results indicate that cells can sense dynamic changes in the surrounding
      environment but the sensitivity depends on cell types.

PMID- 24451136
TI  - Role of insulin-transferrin-selenium in auricular chondrocyte proliferation and
      engineered cartilage formation in vitro.
AB  - The goal of this study is to determine the effects of Insulin-Transferrin
      Selenium (ITS) on proliferation of auricular chondrocytes and formation of
      engineered cartilage in vitro. Pig auricular monolayer chondrocytes and
      chondrocyte pellets were cultured in media containing 1% ITS at different
      concentrations of fetal bovine serum (FBS, 10%, 6%, 2%, 0%), or 10% FBS alone as
      a control for four weeks. Parameters including cell proliferation in monolayer,
      wet weight, collagen type I/II/X (Col I, II, X) and glycosaminoglycan (GAG)
      expression, GAG content of pellets and gene expression associated with cartilage
      formation/dedifferentiation (lost cartilage phenotype)/hypertrophy within the
      chondrocyte pellets were assessed. The results showed that chondrocytes
      proliferation rates increased when FBS concentrations increased (2%, 6%, 10% FBS)
      in ITS supplemented groups. In addition, 1% ITS plus 10% FBS significantly
      promoted cell proliferation than 10% FBS alone. No chondrocytes grew in ITS alone
      medium. 1% ITS plus 10% FBS enhanced cartilage formation in terms of size, wet
      weight, cartilage specific matrices, and homogeneity, compared to 10% FBS alone
      group. Furthermore, ITS prevented engineered cartilage from dedifferentiation
      (i.e., higher index of Col II/Col I mRNA expression and expression of aggrecan)
      and hypertrophy (i.e., lower mRNA expression of Col X and MMP13). In conclusion,
      our results indicated that ITS efficiently enhanced auricular chondrocytes
      proliferation, retained chondrogenic phenotypes, and promoted engineered
      cartilage formation when combined with FBS, which is potentially used as key
      supplementation in auricular chondrocytes and engineered cartilage culture. 

PMID- 24451137
TI  - Egr-1 upregulates Siva-1 expression and induces cardiac fibroblast apoptosis.
AB  - The early growth response transcription factor Egr-1 controls cell specific
      responses to proliferation, differentiation and apoptosis. Expression of Egr-1
      and downstream transcription is closely controlled and cell specific upregulation
      induced by processes such as hypoxia and ischemia has been previously linked to
      multiple aspects of cardiovascular injury. In this study, we showed constitutive
      expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used
      adenoviral mediated gene transfer to study the effects of continuous Egr-1
      overexpression and studied downstream transcription by Western blotting,
      immunohistochemistry and siRNA transfection. Apoptosis was assessed by
      fluorescence microscopy and flow cytometry in the presence of caspase inhibitors.
      Overexpression of Egr-1 directly induced apoptosis associated with caspase
      activation in human cardiac fibroblast cultures in vitro assessed by fluorescence
      microscopy and flow cytometry. Apoptotic induction was associated with a caspase
      activation associated loss of mitochondrial membrane potential and transient
      downstream transcriptional up-regulation of the pro-apoptotic gene product Siva
      1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated
      loss of cell viability. These findings suggest a previously unknown role for Egr
      1 and transcriptional regulation of Siva-1 in the control of cardiac accessory
      cell death. 

PMID- 24451138
TI  - Phosphorylation of histone H2AX in the mouse brain from development to
      senescence.
AB  - Phosphorylation of the histone H2AX (gammaH2AX form) is an early response to DNA
      damage and a marker of aging and disease in several cells and tissues outside the
      nervous system. Little is known about in vivo phosphorylation of H2AX in neurons,
      although it was suggested that gammaH2AX is an early marker of neuronal
      endangerment thus opening the possibility to target it as a neuroprotective
      strategy. After experimental labeling of DNA-synthesizing cells with 5-bromo-2
      deoxyuridine (BrdU), we studied the brain occurrence of gammaH2AX in developing,
      postnatal, adult and senescent (2 years) mice by light and electron microscopic
      immunocytochemistry and Western blotting. Focal and/or diffuse gammaH2AX
      immunostaining appears in interkinetic nuclei, mitotic chromosomes, and apoptotic
      nuclei. Immunoreactivity is mainly associated with neurogenetic areas, i.e., the
      subventricular zone (SVZ) of telencephalon, the cerebellar cortex, and, albeit to
      a much lesser extent, the subgranular zone of the hippocampal dentate gyrus. In
      addition, gammaH2AX is highly expressed in the adult and senescent cerebral
      cortex, particularly the piriform cortex. Double labeling experiments demonstrate
      that gammaH2AX in neurogenetic brain areas is temporally and functionally related
      to proliferation and apoptosis of neuronal precursors, i.e., the type C transit
      amplifying cells (SVZ) and the granule cell precursors (cerebellum). Conversely,
      gammaH2AX-immunoreactive cortical neurons incorporating the S phase-label BrdU do
      not express the proliferation marker phosphorylated histone H3, indicating that
      these postmitotic cells undergo a significant DNA damage response. Our study
      paves the way for a better comprehension of the role of H2AX phosphorylation in
      the normal brain, and offers additional data to design novel strategies for the
      protection of neuronal precursors and mature neurons in central nervous system
      (CNS) degenerative diseases.

PMID- 24451139
TI  - Genetic variants of GPER/GPR30, a novel estrogen-related G protein receptor, are
      associated with human seminoma.
AB  - Testicular germ cell tumors (TGCTs) are the most common solid cancers in young
      men, with an increasing incidence over several years. However, their pathogenesis
      remains a matter of debate. Some epidemiological data suggest the involvement of
      both environmental and genetic factors. We reported two distinct effects of
      estrogens and/or xeno-estrogens on in vitro human seminoma-derived cells
      proliferation: (1) an antiproliferative effect via a classical estrogen receptor
      beta-dependent pathway, and (2) a promotive effect via a non-classical membrane G
      protein-coupled receptor, GPR30/GPER, which is only overexpressed in seminomas,
      the most common TGCT. In order to explain this overexpression, we investigated
      the possible association of polymorphisms in the GPER gene by using allele
      specific tetra-primer polymerase chain reaction performed on tissue samples from
      150 paraffin-embedded TGCT specimens (131 seminomas, 19 non seminomas). Compared
      to control population, loss of homozygous ancestral genotype GG in two
      polymorphisms located in the promoter region of GPER (rs3808350 and rs3808351)
      was more frequent in seminomas but not in non-seminomas (respectively, OR = 1.960
      (1.172-3.277) and 7.000 (2.747-17.840); p < 0.01). These polymorphisms may
      explain GPER overexpression and represent a genetic factor of susceptibility
      supporting the contribution of environmental GPER ligands in testicular
      carcinogenesis. 

PMID- 24451140
TI  - Magnetic nanoparticles as intraocular drug delivery system to target retinal
      pigmented epithelium (RPE).
AB  - One of the most challenging efforts in drug delivery is the targeting of the eye.
      The eye structure and barriers render this organ poorly permeable to drugs. Quite
      recently the entrance of nanoscience in ocular drug delivery has improved the
      penetration and half-life of drugs, especially in the anterior eye chamber, while
      targeting the posterior chamber is still an open issue. The retina and the
      retinal pigment epithelium/choroid tissues, located in the posterior eye chamber,
      are responsible for the majority of blindness both in childhood and adulthood. In
      the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular
      drug delivery that is capable of specific localization in the retinal pigmented
      epithelium (RPE) layer. We demonstrate that, following intraocular injection in
      Xenopus embryos, MNPs localize specifically in RPE where they are retained for
      several days. The specificity of the localization did not depend on particle size
      and surface properties of the MNPs used in this work. Moreover, through similar
      experiments in zebrafish, we demonstrated that the targeting of RPE by the
      nanoparticles is not specific for the Xenopus species. 

PMID- 24451141
TI  - Intravitreal injection of ranibizumab and CTGF shRNA improves retinal gene
      expression and microvessel ultrastructure in a rodent model of diabetes.
AB  - Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have
      been used to treat neovascularization and macular edema. However, anti-VEGF
      treatment alone may cause up-regulation of connective tissue growth factor (CTGF)
      in the retina, increasing the risk of fibrosis and tractional retinal detachment.
      Therefore, in this study, we employ a novel dual-target intervention that
      involves intravitreal injection of the VEGF inhibitor ranibizumab and a
      transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin
      RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the
      dual-target intervention on the expression of VEGF and CTGF and on microvessel
      ultrastructure were examined in retina of streptozocin-induced diabetic rats.
      CTGF was significantly up-regulated at week 8 after diabetic induction, whereas
      VEGF was not up-regulated until week 10. The high expression of both genes was
      maintained at week 12. Transmission electron microscopy also revealed progressive
      exacerbation of microvessel ultrastructure during the same period. In addition,
      ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA
      significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas.
      Importantly, dual-target intervention normalized the transcript levels of both
      target genes and ameliorated retinal microvessel ultrastructural damage better
      than either single-target intervention. These results suggest the advantages of
      dual-target over single-target interventions in diabetic retina and reveal a
      novel therapeutic modality for diabetic retinopathy. 

PMID- 24451142
TI  - Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH
      SY5Y cells through induction of heme oxygenase-1 dependent autophagy.
AB  - Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a
      progressive loss of dopaminergic neurons. Mitochondrial dysfunction, oxidative
      stress or protein misfolding and aggregation may underlie this process. Autophagy
      is an intracellular catabolic mechanism responsible for protein degradation and
      recycling of damaged proteins and cytoplasmic organelles. Autophagic dysfunction
      may hasten the progression of neuronal degeneration. In this study, resveratrol
      promoted autophagic flux and protected dopaminergic neurons against rotenone
      induced apoptosis. In an in vivo PD model, rotenone induced loss of dopaminergic
      neurons, increased oxidation of mitochondrial proteins and promoted autophagic
      vesicle development in brain tissue. The natural phytoalexin resveratrol
      prevented rotenone-induced neuronal apoptosis in vitro, and this pro-survival
      effect was abolished by an autophagic inhibitor. Although both rotenone and
      resveratrol promoted LC3-II accumulation, autophagic flux was inhibited by
      rotenone and augmented by resveratrol. Further, rotenone reduced heme oxygenase-1
      (HO-1) expression, whereas resveratrol increased HO-1 expression. Pharmacological
      inhibition of HO-1 abolished resveratrol-mediated autophagy and neuroprotection.
      Notably, the effects of a pharmacological inducer of HO-1 were similar to those
      of resveratrol, and protected against rotenone-induced cell death in an autophagy
      dependent manner, validating the hypothesis of HO-1 dependent autophagy in
      preventing neuronal death in the in vitro PD model. Collectively, our findings
      suggest that resveratrol induces HO-1 expression and prevents dopaminergic cell
      death by regulating autophagic flux; thus protecting against rotenone-induced
      neuronal apoptosis. 

PMID- 24451144
TI  - The hOGG1 Ser326Cys gene polymorphism and the risk of coronary ectasia in the
      Chinese population.
AB  - Oxidative stress (OS) is related to vascular inflammation possibly, contributing
      to the development of coronary ectasia (CE). Base excision repair (BER) and
      nucleotide excision repair are the main DNA repair pathways that can help to
      remove 8-hydroxydeoxyguanine (8-OHdG), a marker of OS. Human 8-oxoguanine DNA
      glycosylase 1 (hOGG1) is a key enzyme of the BER pathway and catalyzes the
      removal of 8-OHdG. The aim of our study was to investigate the association
      between hOGG1 Ser326Cys gene polymorphism and CE in a Chinese population. Five
      hundred forty-seven patients who underwent diagnostic coronary angiography in a
      tertiary medical center were recruited. The angiographic definition of CE is the
      diameter of the ectatic segment being more than 1.5 times larger compared with an
      adjacent healthy reference segment. The gene polymorphisms were analyzed by
      polymerase chain reaction. The urine 8OHdG concentration was measured using a
      commercial ELISA kit. The distribution of hOGG1 Ser326Cys genotypes was
      significantly different between CE and non-CE groups (p = 0.033). The odds ratio
      of CE development for the Ser to the Cys variant was 1.55 (95% confidence
      interval (CI), 1.04-2.31, p = 0.033). Both univariate and logistic regression
      analysis showed a significant association of hOGG1 Ser326Cys polymorphism in the
      dominant model with CE development (p = 0.009 and 0.011, respectively). Urine 8
      OHdG levels were significantly higher in subjects carrying the hOGG1 Ser variant
      than in those with the Cys/Cys genotype (p < 0.03). In conclusion, our study
      suggests that the hOGG1 Ser326Cys gene variant might play a role in
      susceptibility to the development of CE. 

PMID- 24451143
TI  - Signaling involved in hair follicle morphogenesis and development.
AB  - Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling
      pathways interplay between epithelial and mesenchymal cells. The Wnt pathway
      plays an essential role during hair follicle induction, Shh is involved in
      morphogenesis and late stage differentiation, Notch signaling determines stem
      cell fate while BMP is involved in cellular differentiation. The Wnt pathway is
      considered to be the master regulator during hair follicle morphogenesis. Wnt
      signaling proceeds through EDA/EDAR/NF-kappaB signaling. NF-kappaB regulates the
      Wnt pathway and acts as a signal mediator by upregulating the expression of Shh
      ligand. Signal crosstalk between epithelial and mesenchymal cells takes place
      mainly through primary cilia. Primary cilia formation is initiated with
      epithelial laminin-511 interaction with dermal beta-1 integrin, which also
      upregulates expression of downstream effectors of Shh pathway in dermal lineage.
      PDGF signal transduction essential for crosstalk is mediated through epithelial
      PDGF-A and PDGFRalpha expressed on the primary cilia. Dermal Shh and PDGF
      signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of
      BMP signaling which helps in counteracting BMP mediated beta-catenin inhibition.
      This interplay of signaling between the epithelial and dermal lineage helps in
      epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation
      of epithelial Notch expression. Dysregulation of these pathways leads to certain
      abnormalities and in some cases even tumor outgrowth. 

PMID- 24451146
TI  - Assessment of osteopontin in early breast cancer: correlative study in a
      randomised clinical trial.
AB  - INTRODUCTION: Osteopontin (OPN) is a malignancy-associated glycoprotein that
      contributes functionally to tumor aggressiveness. In metastatic breast cancer, we
      previously demonstrated that elevated OPN in primary tumor and blood was
      associated with poor prognosis. METHODS: We measured OPN in plasma by ELISA, and
      in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of
      667 postmenopausal women with hormone responsive early breast cancer treated by
      surgery followed by adjuvant treatment with tamoxifen +/- octreotide in a
      randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical
      Trials Group Mammary.14). RESULTS: Plasma OPN was measured in 2,540 samples; 688
      at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46
      ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean
      percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was
      no correlation between plasma and tumor OPN values. In multivariate analysis,
      neither was associated with event-free survival (EFS), relapse-free survival
      (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis
      in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9
      to 543) in the recurrence period compared with baseline levels. CONCLUSIONS: The
      hypothesis that OPN tumor expression would have independent prognostic value in
      early breast cancer was not supported by multivariate analysis of this study
      population. Plasma OPN levels in women with hormone responsive early breast
      cancer in the MA.14 trial were not elevated and there was no evidence for
      prognostic value of plasma OPN in this defined group of patients. However, our
      finding of elevated mean OPN plasma level around the time of recurrence warrants
      further study. TRIAL REGISTRATION: NCT00002864,
      http://clinicaltrials.gov/show/NCT00002864.

PMID- 24451147
TI  - Atorvastatin prevents ATP-driven invasiveness via P2X7 and EHBP1 signaling in
      PTEN-expressing prostate cancer cells.
AB  - Epidemiological studies indicate that statins, cholesterol-lowering drugs,
      prevent aggressive prostate cancer and other types of cancer. Employing
      essentially non-prostate cell lines, we previously showed that statins rapidly
      downregulate nuclear levels of phosphorylated Akt via P2X7, a purinergic receptor
      recently implicated in invasive growth. Here, we present studies on phosphatase
      and tensin homolog deleted on chromosome 10 (PTEN)-positive prostatic cells. We
      document an involvement of EH domain-binding protein 1 (EHBP1), previously
      associated with aggressive prostate cancer and insulin-stimulated trafficking and
      cell migration, in P2X7 signaling. We also show that EHBP1 is essential for an
      anti-invasive effect of atorvastatin. Furthermore, EHBP1 interacted with P-Rex1,
      a guanine nucleotide exchange factor previously implicated in invasive growth.
      Mevalonate did not prevent this anti-invasive effect of atorvastatin. These data
      indicate that atorvastatin modulates invasiveness via P2X7, EHBP1 and P-Rex1.
      Interestingly, the interaction between EHBP1 and P-Rex1 was not induced by
      extracellular adenosine triphosphate (ATP), the endogenous P2X7 ligand, and
      statins counteracted invasiveness stimulated by extracellular ATP. In support of
      these experimental data, a population-based genetic analysis showed that a loss
      of function allele in the P2X7 gene (rs3751143) associated with non-aggressive
      cancer, and the common allele with aggressive cancer. Our data indicate a novel
      signaling pathway that inhibits invasiveness and that is druggable. Statins may
      reduce the risk of aggressive prostate cancer via P2X7 and by counteracting
      invasive effects of extracellular ATP.

PMID- 24451149
TI  - Mixed emotional and physical symptoms in general practice: what diagnoses do GPs
      use to describe them?
AB  - AIMS: To determine what diagnostic terms are utilized by general practitioners
      (GPs) when seeing patients with mixed emotional and physical symptoms. METHOD:
      Prototype cases of depression, anxiety, hypochondriasis, somatization and
      undifferentiated somatoform disorders were sourced from the psychiatric
      literature and the author's clinical practice. These were presented, in paper
      form, to a sample of GPs and GP registrars who were asked to provide a written
      diagnosis. RESULTS: Fifty-two questionnaires were returned (30% response rate).
      The depression and anxiety cases were identified correctly by most participants.
      There was moderate identification of the hypochondriasis and somatization
      disorder cases, and poor identification of the undifferentiated somatoform case.
      CONCLUSION: Somatization and undifferentiated somatoform disorders were
      infrequently recognized as diagnostic categories by the GPs in this study. Future
      research into the language and diagnostic reasoning utilized by GPs may help
      develop better diagnostic classification systems for use in primary care in this
      important area of practice.

PMID- 24451148
TI  - Speckle-type POZ protein, SPOP, is involved in the DNA damage response.
AB  - Speckle-type POZ protein (SPOP) is an adaptor of the cullin 3-based ubiquitin
      ligase responsible for the degradation of oncoproteins frequently overexpressed
      in many tumor cells. Altered expression and somatic mutations of SPOP have been
      observed in various tumor types with chromosomal aberrations, indicating a role
      of SPOP in maintaining genome stability, although a detailed mechanism remains
      unclear. Here, we show that SPOP is a component of the DNA damage response (DDR).
      SPOP is recruited to DNA double-strand break sites and it forms nuclear foci
      after DNA damage. SPOP foci colocalize with gamma-H2AX foci and are predominantly
      dependent on the activity of the ataxia-telangiectasia mutated (ATM) kinase.
      Furthermore, SPOP interacts with ATM in response to DNA damage. Finally, we
      demonstrate that knocking down of SPOP resulted in an impaired DDR and a
      hypersensitivity to ionizing irradiation. Together, we highlight a critical role
      of SPOP in the DDR. 

PMID- 24451150
TI  - Implementation of EUnetHTA core Model(r) in Lombardia: the VTS framework.
AB  - OBJECTIVES: This study describes the health technology assessment (HTA) framework
      introduced by Regione Lombardia to regulate the introduction of new technologies.
      The study outlines the process and dimensions adopted to prioritize, assess and
      appraise the requests of new technologies. METHODS: The HTA framework
      incorporates and adapts elements from the EUnetHTA Core Model and the EVIDEM
      framework. It includes dimensions, topics, and issues provided by EUnetHTA Core
      Model to collect data and process the assessment. Decision making is instead
      supported by the criteria and Multi-Criteria Decision Analysis technique from the
      EVIDEM consortium. RESULTS: The HTA framework moves along three process stages:
      (i) prioritization of requests, (ii) assessment of prioritized technology, (iii)
      appraisal of technology in support of decision making. Requests received by
      Regione Lombardia are first prioritized according to their relevance along eight
      dimensions (e.g., costs, efficiency and efficacy, organizational impact, safety).
      Evidence about the impacts of the prioritized technologies is then collected
      following the issues and topics provided by EUnetHTA Core Model. Finally, the
      Multi-Criteria Decision Analysis technique is used to appraise the novel
      technology and support Regione Lombardia decision making. CONCLUSIONS: The VTS
      (Valutazione delle Tecnologie Sanitarie) framework has been successfully
      implemented at the end of 2011. From its inception, twenty-six technologies have
      been processed.

PMID- 24451151
TI  - Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese
      patients infected with hepatitis C genotype 1.
AB  - BACKGROUND: New direct-acting antiviral agents are currently being developed to
      treat chronic HCV. The efficacy and safety of daclatasvir combined with
      peginterferon alfa-2a (alfa-2a) and ribavirin were assessed in a randomized,
      double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1
      infection. METHODS: Japanese patients who were treatment-naive (n=25) or prior
      null (n=12) or partial (n=5) responders received once-daily daclatasvir 10 mg or
      60 mg or placebo in combination with alfa-2a and ribavirin. Daclatasvir
      recipients with a protocol-defined response (HCV RNA<15 IU/ml at week 4 and
      undetectable at week 12) were treated for 24 weeks; placebo recipients and
      patients without a protocol-defined response were treated for 48 weeks. RESULTS:
      Sustained virological response at 24 weeks post-treatment (SVR24) was achieved by
      89% and 100% of treatment-naive patients receiving daclatasvir 10 mg and 60 mg,
      respectively, versus 75% in placebo recipients. Virological failure was more
      frequent in prior non-responder patients, with 50% and 78% achieving SVR24 in
      daclatasvir 10 mg and 60 mg groups, respectively. Adverse events occurred with
      similar frequency among treatment groups and were consistent with the adverse
      event profile of alfa-2a/ribavirin alone. The most commonly reported adverse
      events included pyrexia, alopecia, anaemia, lymphopenia, neutropenia, pruritus
      and diarrhoea. Three patients discontinued treatment due to anaemia. CONCLUSIONS:
      Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed
      greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated.
      The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both
      treatment-naive and non-responder populations and will be evaluated in a Phase
      III clinical trial.

PMID- 24451152
TI  - Engineering of human hepatic tissue with functional vascular networks.
AB  - Although absolute organ shortage highlights the needs of alternative organ
      sources for regenerative medicine, the generation of a three-dimensional (3D) and
      complex vital organ, such as well-vascularized liver, remains a challenge. To
      this end, tissue engineering holds great promise; however, this approach is
      significantly limited by the failure of early vascularization in vivo after
      implantation. Here, we established a stable 3D in vitro pre-vascularization
      platform to generate human hepatic tissue after implantation in vivo. Human fetal
      liver cells (hFLCs) were mixed with human umbilical vein endothelial cells
      (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a
      collagen/fibronectin matrix composite that was used as a 3-D carrier. After a
      couple of days, the fluorescent HUVECs developed premature vascular networks in
      vitro, which were stabilized by hMSCs. The establishment of functional vessels
      inside the pre-vascularized constructs was proven using dextran infusion studies
      after implantation under a transparency cranial window. Furthermore, dynamic
      morphological changes during embryonic liver cell maturation were intravitaly
      quantified with high-resolution confocal microscope analysis. The engineered
      human hepatic tissue demonstrated multiple liver-specific features, both
      structural and functional. Our new techniques discussed here can be implemented
      in future clinical uses and industrial uses, such as drug testing. 

PMID- 24451153
TI  - Colonization patterns of soil microbial communities in the Atacama Desert.
AB  - BACKGROUND: The Atacama Desert is one of the driest deserts in the world and its
      soil, with extremely low moisture, organic carbon content, and oxidizing
      conditions, is considered to be at the dry limit for life. RESULTS: Analyses of
      high throughput DNA sequence data revealed that bacterial communities from six
      geographic locations in the hyper-arid core and along a North-South moisture
      gradient were structurally and phylogenetically distinct (ANOVA test for observed
      operating taxonomic units at 97% similarity (OTU0.03), P <0.001) and that
      communities from locations in the hyper-arid zone displayed the lowest levels of
      diversity. We found bacterial taxa similar to those found in other arid soil
      communities with an abundance of Rubrobacterales, Actinomycetales,
      Acidimicrobiales, and a number of families from the Thermoleophilia. The
      extremely low abundance of Firmicutes indicated that most bacteria in the soil
      were in the form of vegetative cells. Integrating molecular data with climate and
      soil geochemistry, we found that air relative humidity (RH) and soil conductivity
      significantly correlated with microbial communities' diversity metrics (least
      squares linear regression for observed OTU0.03 and air RH and soil conductivity,
      P <0.001; UniFrac PCoA Spearman's correlation for air RH and soil conductivity, P
      <0.0001), indicating that water availability and salt content are key factors in
      shaping the Atacama soil microbiome. Mineralization studies showed communities
      actively metabolizing in all soil samples, with increased rates in soils from the
      southern locations. CONCLUSIONS: Our results suggest that microorganisms in the
      driest soils of the Atacama Desert are in a state of stasis for most of the time,
      but can potentially metabolize if presented with liquid water for a sufficient
      duration. Over geological time, rare rain events and physicochemical factors
      potentially played a major role in selecting micro-organisms that are most
      adapted to extreme desiccating conditions.

PMID- 24451155
TI  - Happiness intervention decreases pain and depression, boosts happiness among
      primary care patients.
AB  - AIM: The aim of the study was to determine whether positive psychological
      interventions (PPIs) in a primary health care setting would improve physical and
      mental health over time. BACKGROUND: Most treatments for depression focus on
      reducing symptoms rather than on creating positive states of mental health.
      Empirical studies to verify the efficacy of PPIs in primary health care are
      needed. METHOD: In a six-week pilot program, we invited patients in a primary
      health care setting with symptoms of depression to participate in groups designed
      to increase levels of happiness. The program involved interventions such as
      engaging in good deeds, writing gratitude letters, and introducing empirical
      research. Patients completed the SF12v2((r)) at the beginning and end of the
      program and at three- and six-month follow-up. Measures included physical
      functioning, bodily pain, mental health, social functioning, and vitality.
      Patients also participated in focus groups to discuss their experiences.
      FINDINGS: Of the 124 patients who enrolled in this pilot study, 75 completed the
      six-week program, and 35 participated in two follow-up assessments. Among the
      participants who remained for all follow-up assessments, scores improved from
      baseline to 6-month follow-up for health, vitality, mental health, and the
      effects of mental and physical health on daily activities. This subset of
      patients reported greater energy and more daily accomplishments, along with
      reductions in functional limitations. Improvements in mental and physical health
      and functioning were shown over a six-month period. The study provides a basis
      for the further investigation of PPIs in creating improvements for patients with
      depression in primary health care.

PMID- 24451156
TI  - Colloidal ZnO nanocrystals in dimethylsulfoxide: a new synthesis, optical, photo-
      and electroluminescent properties.
AB  - Stable colloidal solutions of zinc oxide in dimethylsulfoxide were synthesized
      via interaction between zinc(II) acetate and tetraalkylammonium hydroxides (alkyl
      ethyl, propyl, butyl, and pentyl). Colloids of ZnO emit photoluminescence in a
      broad band with a maximum at 2.3-2.4 eV with quantum yields of up to 9-10% at
      room temperature and 15-16% at 80 K. The photoluminescence is supposed to
      originate from the radiative recombination of conduction band electrons with
      holes captured by deep traps having corresponding states in the band gap 1.0-1.2
      eV above the valence band edge. The size of colloidal ZnO nanocrystals depends on
      the duration and temperature of the post-synthesis treatment and varies in the
      range of 3-6 nm. Growth of the ZnO nanocrystals can be terminated at any moment
      of the thermal treatment by freezing the colloidal solution or by addition of
      tetraethyl orthosilicate which hydrolyses forming core-shell ZnO@SiO2 particles.
      ZnO nanocrystals introduced into polyethyleneimine films can be used as an active
      component of an LED emitting at an applied voltage higher than 13 V.

PMID- 24451157
TI  - Rapid review: an emerging approach to evidence synthesis in health technology
      assessment.
AB  - BACKGROUND: Increasingly, healthcare decision makers demand quality evidence in a
      short timeframe to support urgent and emergent decisions related to procurement,
      clinical practice, and policy. Health technology assessment (HTA) producers are
      responding by developing innovative approaches to evidence synthesis that can be
      executed more quickly than traditional systematic review. These approaches, and
      the broader implications they bring to bear on health decision making and policy
      development, however, are generally neither well-understood nor well-described.
      This study intends to contribute to an emerging literature around methodological
      approaches to rapid review in HTA by outlining those developed and implemented by
      the Canadian Agency for Drugs and Technologies in Health (CADTH). METHODS: Since
      2005, CADTH has developed and implemented a rapid review approach that
      synthesizes evidence to support informed healthcare decisions and policy. Rapid
      Response reports are tailored to the identified needs of Canadian health decision
      makers, representing a range of options with regard to depth, breadth, and time
      to-delivery. RESULTS: Preliminary observations indicate that CADTH's approach to
      rapid evidence review is generally well-received by Canadian health decision
      makers; real-world case studies provide pragmatic examples of how health decision
      makers have used Rapid Response reports to support evidence-informed health
      decisions across Canada. CONCLUSIONS: Rapid review is becoming an increasingly
      important approach to evidence synthesis, both within and external to the field
      of HTA. Transparent reporting of the methods used to develop rapid review
      products will be critical to the assessment of their relevance, utility and
      effects in a range of contexts.

PMID- 24451154
TI  - Direct inhibition of PI3K in combination with dual HER2 inhibitors is required
      for optimal antitumor activity in HER2+ breast cancer cells.
AB  - INTRODUCTION: Despite multiple advances in the treatment of HER2+ breast cancers,
      resistance develops even to combinations of HER2 targeting agents. Inhibition of
      PI3K pathway signaling is critical for the efficacy of HER2 inhibitors.
      Activating mutations in PIK3CA can overlap with HER2 amplification and have been
      shown to confer resistance to HER2 inhibitors in preclinical studies. METHODS:
      Lapatinib-resistant cells were profiled for mutations in the PI3K pathway with
      the SNaPshot assay. Hotspot PIK3CA mutations were retrovirally transduced into
      HER2-amplified cells. The impact of PIK3CA mutations on the effect of HER2 and
      PI3K inhibitors was assayed by immunoblot, proliferation and apoptosis assays.
      Uncoupling of PI3K signaling from HER2 was investigated by ELISA for
      phosphoproteins in the HER2-PI3K signaling cascade. The combination of HER2
      inhibitors with PI3K inhibition was studied in HER2-amplified xenograft models
      with wild-type or mutant PIK3CA. RESULTS: Here we describe the acquisition of a
      hotspot PIK3CA mutation in cells selected for resistance to the HER2 tyrosine
      kinase inhibitor lapatinib. We also show that the gain of function conferred by
      these PIK3CA mutations partially uncouples PI3K signaling from the HER2 receptor
      upstream. Drug resistance conferred by this uncoupling was overcome by blockade
      of PI3K with the pan-p110 inhibitor BKM120. In mice bearing HER2-amplified wild
      type PIK3CA xenografts, dual HER2 targeting with trastuzumab and lapatinib
      resulted in tumor regression. The addition of a PI3K inhibitor further improved
      tumor regression and decreased tumor relapse after discontinuation of treatment.
      In a PIK3CA-mutant HER2+ xenograft, PI3K inhibition with BKM120 in combination
      with lapatinib and trastuzumab was required to achieve tumor regression.
      CONCLUSION: These results suggest that the combination of PI3K inhibition with
      dual HER2 blockade is necessary to circumvent the resistance to HER2 inhibitors
      conferred by PIK3CA mutation and also provides benefit to HER2+ tumors with wild
      type PIK3CA tumors.

PMID- 24451158
TI  - The origin and emergence of an HIV-1 epidemic: from introduction to endemicity.
AB  - OBJECTIVES: To describe, at patient-level detail, the determining events and
      factors involved in the development of a country's HIV-1 epidemic. DESIGN:
      Clinical information for all recorded Greenlandic HIV-1 patients was analysed and
      correlated with both novel and previously analysed pol sequences, representing
      more than half of the entire Greenlandic HIV-1 epidemic. Archival blood samples
      were sequenced to link early infection chain descriptions to the subsequent
      epidemic. METHODS: In-depth phylogenetic analyses were used in synergy with
      clinical information to assess number of introductions of HIV-1 into Greenland,
      the source of geographic origin, time of epidemic introduction and its
      epidemiological characteristics such as initial transmission chain, geographic
      dispersal within Greenland, method of infection, cluster size, sociological and
      behavioural factors. RESULTS: Despite its small population size and isolated
      geographic location, data support at least 25 introductions of HIV-1 into
      Greenland. Only a single of these led to an epidemic. This introduction occurred
      between 1985 and 1986, and the epidemic cluster is still active. Facilitating
      factors for the emergence and spread of the epidemic cluster include a rapid
      transition from MSM to heterosexual spread, high prevalence of other sexually
      transmitted diseases, rapid dispersal to larger cities and early emergence in a
      distinct subpopulation with high-risk behaviour including disregard for
      condomizing. CONCLUSIONS: The synergistic use of disparate data categories yields
      such unique detail, that the Greenland epidemic now serves as a model example for
      the epidemic emergence of HIV-1 in a society. This renders it suitable for
      testing of present and future sequence-based epidemiological methodologies.

PMID- 24451159
TI  - Efficient transfer of HIV-1 in trans and in cis from Langerhans dendritic cells
      and macrophages to autologous T lymphocytes.
AB  - OBJECTIVE: The chronology of HIV infection in mucosal tissue after sexual
      transmission is unknown. Several potential HIV target cells are present at these
      sites, including dendritic cells, macrophages, and CD4(+) T lymphocytes.
      Dendritic cells and macrophages are antigen-presenting cells (APCs) and are thus
      involved in cross-talk with T cells. This close contact may favor efficient HIV-1
      transfer to T lymphocytes, resulting in rapid HIV-1 dissemination. DESIGN: We
      investigated the role of APCs in HIV transfer to T cells by incubating Langerhans
      cells and interstitial dendritic cells (IDCs) or monocyte-derived macrophages
      (MDMs) with HIV for 2 h before addition of uninfected autologous CD4(+) T
      lymphocytes. METHODS: HIV infection was recorded after different time points.
      Following staining, the measurement of intracellular p24 in the different cell
      populations was analyzed by flow cytometry. RESULTS: We showed that Langerhans
      cells/IDCs and macrophages efficiently transferred HIV to CD4(+) T cells.
      Interestingly, a rapid HIV transfer in trans predominated in MDMs, whereas cis
      transfer mainly occurred in Langerhans cells/IDC cocultures. Neutralizing
      antibody 2G12, added to HIV-loaded APCs, efficiently blocked both the trans and
      the cis infection of T cells. CONCLUSION: These findings highlight the major
      contributions of various mucosal cells in HIV dissemination and suggest that HIV
      hijacks the different properties of APCs to favor its dissemination through the
      body. They emphasize the role of macrophages in the rapid transmission of HIV to
      T lymphocytes at mucosal sites, dendritic cells being prone to migration to
      lymphoid organ for subsequent dissemination by cis transfer.

PMID- 24451160
TI  - HIV drug resistance detected during low-level viraemia is associated with
      subsequent virologic failure.
AB  - BACKGROUND: The clinical implications of emergent HIV drug resistance on samples
      with low-level viraemia (LLV <1000 copies/ml) remain unclear. We undertook the
      present analysis to evaluate the impact of emergent HIV drug resistance at LLV on
      the risk of subsequent virologic failure. METHODS: One thousand, nine hundred and
      sixty-five patients had genotype results at LLV. Risk of virologic failure
      (>=1000 copies/ml) after LLV was evaluated by Kaplan-Meier analysis and Cox
      proportional hazards regression. Resistance was assessed using the Stanford
      algorithm or virtual phenotypes. Patients were grouped into four susceptibility
      categories ('GSS' or 'vPSS') during LLV, corresponding to the number of 'active'
      drugs prescribed: <1; 1-1.5; 2-2.5; and >=3. RESULTS: A total of 1702 patients
      with follow-up on constant therapy were eligible for analysis. Participants
      excluded due to changing therapy or loss to follow-up before their next
      observation had mostly similar characteristics to included participants. There
      was a 'dose-dependent' increase in the hazard ratio for virologic failure with
      susceptibility categories at LLV. Compared with a GSS of at least 3, hazard
      ratios for virologic failure were 1.4 for GSS 2-2.5; 2.0 for GSS 1-1.5; and 3.0
      for GSS less than 1 (P < 0.001). Numerous sensitivity analyses confirmed these
      findings. CONCLUSION: Our results demonstrate that emergent HIV drug resistance
      at LLV is strongly associated with subsequent virologic failure. Furthermore, we
      uncovered a 'dose-dependent' increase in the hazard ratio for virologic failure
      with decreasing GSS estimated at the time of LLV. On the basis of these findings,
      we propose that resistance genotyping be encouraged for HIV-infected individuals
      on antiretroviral therapy experiencing low-level viraemia.

PMID- 24451161
TI  - Social and ethical implications of HIV cure research.

PMID- 24451163
TI  - Daily temporal dynamics of vaginal microbiota before, during and after episodes
      of bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a common gynecologic diagnosis
      characterized by dysbiosis of the vaginal microbiota. It is often accompanied by
      vaginal symptoms such as odor and discharge, but can be asymptomatic. Despite
      over 50 years of research, the etiology of BV is not well understood, which is a
      major impediment to treatment and prevention of BV. RESULTS: Here we report on
      the temporal dynamics of 25 vaginal communities over a 10 week period using
      samples collected daily from women who were diagnosed with symptomatic BV (15
      women), asymptomatic BV (6 women), and women who did not have BV (4 women).
      CONCLUSION: This unique resource of samples and data will contribute to a better
      understanding of the role that the vaginal microbes have in the natural history
      of BV and lead to improved diagnosis and treatment.

PMID- 24451164
TI  - Modelling of a biologically inspired robotic fish driven by compliant parts.
AB  - Inspired by biological swimmers such as fish, a robot composed of a rigid head, a
      compliant body and a rigid caudal fin was built. It has the geometrical
      properties of a subcarangiform swimmer of the same size. The head houses a servo
      motor which actuates the compliant body and the caudal fin. It achieves this by
      applying a concentrated moment on a point near the compliant body base. In this
      paper, the dynamics of the compliant body driving the robotic fish is modelled
      and experimentally validated. Lighthill's elongated body theory is used to define
      the hydrodynamic forces on the compliant part and Rayleigh proportional damping
      is used to model damping. Based on the assumed modes method, an energetic
      approach is used to write the equations of motion of the compliant body and to
      compute the relationship between the applied moment and the resulting lateral
      deflections. Experiments on the compliant body were carried out to validate the
      model predictions. The results showed that a good match was achieved between the
      measured and predicted deformations. A discussion of the swimming motions between
      the real fish and the robot is presented. 

PMID- 24451162
TI  - Compartmentalization of innate immune responses in the central nervous system
      during cryptococcal meningitis/HIV coinfection.
AB  - OBJECTIVE: The role of innate immunity in the pathogenesis of cryptococcal
      meningitis is unclear. We hypothesized that natural killer (NK) cell and monocyte
      responses show central nervous system (CNS) compartment-specific profiles, and
      are altered by antifungal therapy and combination antiretroviral therapy (cART)
      during cryptococcal meningitis/HIV coinfection. DESIGN: Substudy of a prospective
      cohort study of adults with cryptococcal meningitis/HIV coinfection in Durban,
      South Africa. METHODS: We used multiparametric flow cytometry to study
      compartmentalization of subsets, CD69 (a marker of activation), CXCR3 and CX3CR1
      expression, and cytokine secretion of NK cells and monocytes in freshly collected
      blood and cerebrospinal fluid (CSF) at diagnosis (n = 23), completion of
      antifungal therapy induction (n = 19), and after a further 4 weeks of cART (n =
      9). RESULTS: Relative to blood, CSF was enriched with CD56(bright)
      (immunoregulatory) NK cells (P = 0.0004). At enrolment, CXCR3 expression was more
      frequent among blood CD56(bright) than either blood CD56(dim) (P < 0.0001) or CSF
      CD56(bright) (P = 0.0002) NK cells. Antifungal therapy diminished blood (P <
      0.05), but not CSF CXCR3(pos) NK-cell proportions nor CX3CR1(pos) NK-cell
      proportions. CD56(bright) and CD56(dim) NK cells were more activated in CSF than
      blood (P < 0.0001). Antifungal therapy induction reduced CD56(dim) NK-cell
      activation in CSF (P = 0.02). Activation of blood CD56(bright) and CD56(dim) NK
      cells was diminished following cART commencement (P < 0.0001, P = 0.03).
      Immunoregulatory NK cells in CSF tended to secrete higher levels of CXCL10 (P =
      0.06) and lower levels of tumor necrosis factor alpha (P = 0.06) than blood
      immunoregulatory NK cells. CSF was enriched with nonclassical monocytes (P =
      0.001), but antifungal therapy restored proportions of classical monocytes (P =
      0.007). CONCLUSION: These results highlight CNS activation, trafficking, and
      function of NK cells and monocytes in cryptococcal meningitis/HIV and implicate
      immunoregulatory NK cells and proinflammatory monocytes as potential modulators
      of cryptococcal meningitis pathogenesis during HIV coinfection.

PMID- 24451165
TI  - The progression of peroxisomal degradation through autophagy requires peroxisomal
      division.
AB  - Peroxisomes are highly dynamic organelles that have multiple functions in
      cellular metabolism. To adapt the intracellular conditions to the changing
      extracellular environment, peroxisomes undergo constitutive segregation and
      degradation. The segregation of peroxisomes is mediated by 2 dynamin-related
      GTPases, Dnm1 and Vps1, whereas, the degradation of peroxisomes is accomplished
      through pexophagy, a selective type of autophagy. During pexophagy, the size of
      the organelle is always a challenging factor for the efficiency of engulfment by
      the sequestering compartment, the phagophore, which implies a potential role for
      peroxisomal fission in the degradation process, similar to the situation with
      selective mitochondria degradation. In this study, we report that peroxisomal
      fission is indeed critical for the efficient elimination of the organelle. When
      pexophagy is induced, both Dnm1 and Vps1 are recruited to the degrading
      peroxisomes through interactions with Atg11 and Atg36. In addition, we found that
      specific peroxisomal fission, which is only needed for pexophagy, occurs at
      mitochondria-peroxisome contact sites. 

PMID- 24451166
TI  - Data on the utilization of treatment modalities for ED in Taiwan in the era of
      PDE5 inhibitors.
AB  - Oral PDE5 inhibitors, intracavernosal injection and penile implants are mainstay
      treatments for ED. Data on their utilization reflect economic aspects of ED, but
      are underreported. We report utilization data and user characteristics for these
      modalities in Taiwan between 1999 and 2011. Sales data on PDE5 inhibitors
      sildenafil citrate, tadalafil and vardenafil and on alprostadil were retrieved
      from International Market Services Health, and on penile implants from the local
      importing company for them. Users' clinical characteristics were derived from one
      institution. Between 1999 and 2011, sales of PDE5 inhibitors increased 5.9-fold,
      whereas those of alprostadil and penile implants remained stable. Over 90% of
      PDE5 inhibitors were purchased in pharmacies without a prescription. Between 1999
      and 2011, the number of patients who received PDE5 inhibitors (n=4715) exceeded
      those who underwent penile injection (n=333) and penile implantation (n=108). The
      mean age of patients with ED who first received PDE5 inhibitors tended to
      decrease over consecutive years. Discontinuation of treatment with PDE5
      inhibitors or intracavernosal injection reached 90% within 3 years of treatment
      initiation. Our data on the increasing market for PDE5 inhibitors and the trend
      for first use of PDE5 inhibitors at younger ages highlight the growing burden of
      ED and the acceptance of PDE5 inhibitors as the primary treatment for ED. 

PMID- 24451167
TI  - Changes in sexual inhibition and excitation during PDE5I therapy.
AB  - The aim of this longitudinal study was to assess possible changes in sexual
      inhibition and excitation (measured using the Sexual Inhibition and Sexual
      Excitation Scales (SIS/SES)) in men being treated with PDE5 inhibitors (PDE5I)
      for ED. Established PDE5I users diagnosed with psychogenic ED completed the
      SES/SIS questionnaire at recruitment and 3 months later. On the basis of
      International Index of Erectile Function scores at recruitment, subjects were
      divided into two groups - mildly affected (M) and mild-to-moderately affected
      (MM). SES scores were significantly lower, and SIS1 scores were significantly
      higher in Group MM at recruitment and at 3 months (P<0.001). In Group M, SES
      scores increased (P<0.005) and SIS1 (P<0.001) and SIS2 (P=0.01) scores decreased
      over the 3 months of the study. In Group MM, ongoing decreases in SES and
      increases in SIS1 scores were observed (P<0.001). The results of multiple linear
      regression showed that SIS/SES variables were of little value in predicting
      erectile function (EF) at recruitment, or changes in EF during the study period.
      The results for Group M showed that men whose EF scores increased were more
      likely to experience increased SIS2 and decreased SES scores. 

PMID- 24451168
TI  - Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for
      human HER2.
AB  - INTRODUCTION: The availability of mice transgenic for the human HER2 gene
      (huHER2) and prone to the development of HER2-driven mammary carcinogenesis
      (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive
      strategies targeting the human HER2 molecule in a tolerant host. METHODS: FVB
      huHER2 mice were vaccinated with either IL-12-adjuvanted human HER2-positive
      cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and
      number of mammary tumors were recorded to evaluate vaccine potency. Mice sera
      were collected and passively transferred to xenograft-bearing mice to assess
      their antitumor efficacy. RESULTS: Both cell and DNA vaccines significantly
      delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas
      mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of
      45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about
      90 weeks of age. The number of mammary tumors per mouse was also significantly
      reduced in vaccinated mice. Vaccines broke the immunological tolerance to the
      huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine
      mainly induced a high and sustained level of anti-huHER2 antibodies, the cell
      vaccine also elicited interferon (IFN)-gamma production. Sera of DNA-vaccinated
      mice transferred to xenograft-carrying mice significantly inhibited the growth of
      human HER2-positive cancer cells. CONCLUSIONS: Anti-huHER2 antibodies elicited in
      the tolerant host exert antitumor activity.

PMID- 24451169
TI  - Programmable DNA tile self-assembly using a hierarchical sub-tile strategy.
AB  - DNA tile based self-assembly provides a bottom-up approach to construct desired
      nanostructures. DNA tiles have been directly constructed from ssDNA and readily
      self-assembled into 2D lattices and 3D superstructures. However, for more complex
      lattice designs including algorithmic assemblies requiring larger tile sets, a
      more modular approach could prove useful. This paper reports a new DNA 'sub-tile'
      strategy to easily create whole families of programmable tiles. Here, we
      demonstrate the stability and flexibility of our sub-tile structures by
      constructing 3-, 4- and 6-arm DNA tiles that are subsequently assembled into 2D
      lattices and 3D nanotubes according to a hierarchical design. Assembly of sub
      tiles, tiles, and superstructures was analyzed using polyacrylamide gel
      electrophoresis and atomic force microscopy. DNA tile self-assembly methods
      provide a bottom-up approach to create desired nanostructures; the sub-tile
      strategy adds a useful new layer to this technique. Complex units can be made
      from simple parts. The sub-tile approach enables the rapid redesign and
      prototyping of complex DNA tile sets and tiles with asymmetric designs.

PMID- 24451170
TI  - Worker replacement and cost-benefit analysis of life-saving health care programs,
      a precautionary note.
AB  - The assumption according to which ill individuals can be replaced at work that
      underpins the 'friction cost method' (FCM) to value productivity costs has been
      primarily discussed within the framework of cost-utility analysis. This paper
      investigates the consequences of this assumption for cost-benefit analysis (CBA).
      It makes three contributions. First, it provides the first analytical account of
      the overall consequences of ill worker replacement on social welfare and it
      analyzes the associated compensation effects within a CBA framework. Second, it
      highlights a double counting problem that arises when ill worker replacement is
      assumed in the CBA of life-saving health care programs. To the best of our
      knowledge, no satisfactory solution to this problem has yet been provided in the
      literature. Third, this paper suggests and discusses two original ways to address
      this double counting issue. One consists in adjusting value of a statistical life
      estimations for the well-being provided by future incomes. Another possibility
      lies in the estimation of marginal rates of substitution between health and
      wealth so as to directly monetize the value of life over and above consumption.
      We show that both solutions raise unresolved questions that should be addressed
      in future research to enable appropriate use of the FCM in CBA. 

PMID- 24451172
TI  - Pregnancy, cardiomyopathies, and genetics.
AB  - Although familial forms of cardiomyopathy such as hypertrophic or dilated
      cardiomyopathy have been recognized for decades, it is only recently that much of
      the genetic basis of these inherited cardiomyopathies has been elucidated. This
      has provided important insights into the pathophysiological mechanisms underlying
      the disease phenotype. This increased knowledge and the availability of genetic
      testing has resulted in increasing numbers of mutation carriers who are being
      monitored, including many who are now of child-bearing age. Pregnancy is
      generally well tolerated in asymptomatic patients or mutation carriers with
      inherited cardiomyopathies. However, since pregnancy leads to major physiological
      changes in the cardiovascular system, in women with genetic cardiomyopathies or
      who carry a mutation pre-disposing to a genetic cardiomyopathy, pregnancy entails
      a risk of developing heart failure and/or arrhythmias. This deterioration of
      cardiac function may occur despite optimal medical treatment. Advanced left
      ventricular dysfunction, poor functional class (NYHA class III or IV), or prior
      cardiac events appear to increase the risk of maternal cardiac complications.
      However, there are no large series of cardiomyopathy patients who are regularly
      evaluated for cardiac complications during pregnancy and for certain types of
      inherited cardiomyopathy, only case reports on individual pregnancies are
      available. Pre-conception cardiologic evaluation and genetic counselling are
      important for every woman with a cardiomyopathy or a cardiomyopathy-related
      mutation who is considering having a family. In this article, we give an overview
      of the basic clinical aspects, genetics, and pregnancy outcome in women with
      different types of inherited cardiomyopathies. We also discuss the genetic
      aspects of pregnancy-associated cardiomyopathy, including peripartum
      cardiomyopathy. 

PMID- 24451173
TI  - Wasteful disposition: analysis of municipal household waste using geodemographic
      classification.
AB  - The continuous flow of resources through the economy is the origin of most of the
      environmental problems evident today. These problems are directly related to
      production and introduction of wastes and pollutants into the natural
      environment. The study investigated the relationship between household waste and
      geodemographic grouping (GDG) at the municipal level across England. A
      correlation analysis of the GDG and waste data revealed a positive relationship
      between waste and proportion of different GDG. A robust regression model
      generated represents 74% of the variation across the dataset, and it shows that
      there is a significant relationship between municipal waste and GDG. A higher
      number of GDG (e.g. 3, 4, 6, 7 and 8) displayed a very strong association with
      increasing total municipal household waste (TMHW). GDG such as 1, 2 and 10,
      despite their higher disposable incomes, displayed a weak association with TMHW.
      Furthermore, GDGs such as 8, 3, 7, 4 and 6 generated more household waste in
      comparison to GDG. This model provides an understanding that can influence the
      organisation of waste management programmes and forecasting of municipal waste.
      It also provides essential input for decisions in structuring promotion of
      sustainable behaviour and implementing local initiatives to support such
      activities. 

PMID- 24451174
TI  - Identification of genes essential for anaerobic growth of Listeria monocytogenes.
AB  - The facultative anaerobic bacterium Listeria monocytogenes encounters
      microaerophilic or anaerobic conditions in various environments, e.g. in soil, in
      decaying plant material, in food products and in the host gut. To elucidate the
      adaptation of Listeria monocytogenes to variations in oxygen tension, global
      transcription analyses using DNA microarrays were performed. In total, 139 genes
      were found to be transcribed differently during aerobic and anaerobic growth; 111
      genes were downregulated and 28 genes were upregulated anaerobically. The oxygen
      dependent transcription of central metabolic genes is in agreement with results
      from earlier physiological studies. Of those genes more strongly expressed under
      lower oxygen tension, 20 were knocked out individually. Growth analysis of these
      knock out mutants did not indicate an essential function for the respective genes
      during anaerobiosis. However, even if not essential, transcriptional induction of
      several genes might optimize the bacterial fitness of Listeria monocytogenes in
      anaerobic niches, e.g. during colonization of the gut. For example, expression of
      the anaerobically upregulated gene lmo0355, encoding a fumarate reductase alpha
      chain, supported growth on 10 mM fumarate under anaerobic but not under aerobic
      growth conditions. Genes essential for anaerobic growth were identified by
      screening a mutant library. Eleven out of 1360 investigated mutants were
      sensitive to anaerobiosis. All 11 mutants were interrupted in the atp locus.
      These results were further confirmed by phenotypic analysis of respective in
      frame deletion and complementation mutants, suggesting that the generation of a
      proton motive force via F1F0-ATPase is essential for anaerobic proliferation of
      Listeria monocytogenes. 

PMID- 24451176
TI  - Detrimental role of humoral signalling in cardio-renal cross-talk.
AB  - In critically ill patients, any acute organ injury is associated with a sudden
      change of circulating factors that may play a role in distant organ dysfunction
      through a complex cross-talk. In this issue, Virzi and colleagues discuss the
      relevance of humoral signalling between heart and kidney, focusing on type 1 and
      type 3 cardio-renal syndrome. We herein review the mechanisms of heart-kidney
      cross-talk, discussing the role of circulating detrimental mediators in the
      pathogenetic mechanisms of cardio-renal syndrome.

PMID- 24451175
TI  - Re-evaluation of liver stem/progenitor cells.
AB  - Liver stem/progenitor cells (LPCs) are defined as cells that supply two types of
      liver epithelial cells, hepatocytes and cholangiocytes, during development,
      cellular turnover, and regeneration. Hepatoblasts, which are fetal LPCs derived
      from endoderm stem cells, robustly proliferate and differentiate into hepatocytes
      and cholangiocytes during fetal life. Between mid-gestation and the neonatal
      period, some cholangiocytes function as LPCs. Although LPCs in adult livers can
      be enriched in cells positive for cholangiocyte markers, their tissue
      localization and functions in cellular turnover remain obscure. On the other
      hand, it is well known that liver regeneration under conditions suppressing
      hepatocyte proliferation is supported by LPCs, though their origin has not been
      clearly identified. Recently many groups took advantage of new techniques
      including prospective isolation of LPCs by fluorescence-activated cell sorting
      and genetic lineage tracing to facilitate our understanding of epithelial supply
      in normal and injured livers. Those works suggest that, in normal livers, the
      turnover of hepatocytes mostly depends on duplication of hepatocytes. It is also
      demonstrated that liver epithelial cells as well as LPCs have great plasticity
      and flexible differentiation capability to respond to various types of injuries
      by protecting or repairing liver tissues. 

PMID- 24451177
TI  - A multibody approach for 6-DOF flight dynamics and stability analysis of the
      hawkmoth Manduca sexta.
AB  - This paper investigates the six degrees of freedom (6-DOF) flight dynamics and
      stability of the hawkmoth Manduca sexta using a multibody dynamics approach that
      encompasses the effects of the time varying inertia tensor of all the body
      segments including two wings. The quasi-steady translational and unsteady
      rotational aerodynamics of the flapping wings are modeled with the blade element
      theory with aerodynamic coefficients derived from relevant experimental studies.
      The aerodynamics is given instantaneously at each integration time step without
      wingbeat-cycle-averaging. With the multibody dynamic model and the aerodynamic
      model for the hawkmoth, a direct time integration of the fully coupled 6-DOF
      nonlinear multibody dynamics equations of motion is performed. First, the passive
      damping magnitude of each single DOF is quantitatively examined with the measure
      of the time taken to half the initial velocity (thalf). The results show that the
      sideslip translation is less damped approximately three times than the other two
      translational DOFs, and the pitch rotation is less damped approximately five
      times than the other two rotational DOFs; each DOF has the value of (unit in
      wingbeat strokes): thalf,forward/backward = 7.10, thalf,sideslip = 17.95,
      thalf,ascending = 7.13, thalf,descending = 5.77, thalf,roll = 0.68, thalf,pitch =
      2.39, and thalf,yaw = 0.25. Second, the natural modes of motion, with the
      hovering flight as a reference equilibrium condition, are examined by analyzing
      fully coupled 6-DOF dynamic responses induced by multiple sets of force and
      moment disturbance combinations. The given disturbance combinations are set to
      excite the dynamic modes identified in relevant eigenmode analysis studies. The 6
      DOF dynamic responses obtained from this study are compared with eigenmode
      analysis results in the relevant studies. The longitudinal modes of motion showed
      dynamic modal characteristics similar to the eigenmode analysis results from the
      relevant literature. However, the lateral modes of motion revealed more complex
      behavior, which is mainly due to the coupling effect in the lateral flight states
      and also between the lateral and longitudinal planes of motion. The main sources
      of the flight instability of the hovering hawkmoth are examined as either the
      longitudinal instability grown from the coupled forward/backward velocity and the
      pitch rate, or the lateral instability grown from the coupled sideslip velocity
      and the roll rate. 

PMID- 24451178
TI  - Cardiac magnetic resonance imaging of congenital bicuspid aortic valves and
      associated aortic pathologies in adults.
AB  - AIMS: Bicuspid aortic valve (BAV) represents the most frequent congenital cardiac
      abnormality resulting in premature valvular degeneration and aortic dilatation.
      In a large series of consecutive patients, we evaluated the distribution of BAV
      types and the associated valvular and aortic abnormalities. METHODS AND RESULTS:
      We investigated 266 patients (58 +/- 14 years) with BAV using a 1.5 T cardiac
      magnetic resonance (CMR) scanner. Valve morphology was described according to the
      Sievers classification. The aortic valve orifice area, aortic regurgitation (AR)
      fraction, and aortic dilation were quantified. Two hundred and forty-two data
      sets were available for analysis; 24% had BAV without a valvular lesion. The
      predominant valvular lesion was aortic stenosis (AS) with 51%. Lone AR was found
      in 17%. A combined lesion of AS and AR was found in 9%. Those with AS were older
      than the overall average (64 +/- 12 vs. 57 +/- 15 years, P < 0.001). The patients
      with AR and those without valvular abnormality were younger than average (49 +/-
      13 and 50 +/- 12 years vs. 57 +/- 15 years, P < 0.01 respectively). Comparing two
      observers Kappa coefficient was 0.77 for differentiation of six valve
      morphologies and 0.80 for the differentiation of bicuspid and tricuspid valve.
      Aortic dilatation was found in 39% of cases with no discernible preference for
      any specific BAV-type and mainly affecting the ascending aorta. CONCLUSION: CMR
      can non-invasively differentiate various morphologies in BAV with low inter
      observer variability. Valvular pathologies vary across age. Aortic dilatation is
      frequent in BAV independent from valvular morphology or lesion. In future CMR
      might help to guide management in patients with BAV.

PMID- 24451179
TI  - Safety and tolerability of regadenoson CMR.
AB  - AIMS: Knowledge of adverse events associated with regadenoson perfusion cardiac
      magnetic resonance (CMR) and patient tolerability has implications for patient
      safety and staff training. We sought to assess the safety and tolerability of
      regadenoson stress CMR. MATERIALS AND METHODS: A group of 728 consecutive
      patients (median age 58, 44% female) and 25 normal volunteers (median age 21, 24%
      female) were recruited from August 2009 to March 2012 using a prospective, cross
      sectional study design. Subjects were stressed using fixed-dose regadenoson and
      imaged using a 1.5T MRI scanner. Symptoms and adverse events including death,
      myocardial infarction (MI), ventricular tachycardia (VT)/ventricular fibrillation
      (VF), hospitalization, arrhythmias, and haemodynamic stability were assessed.
      RESULTS: There were no occurrences of death, MI, VT/VF, high-grade
      atrioventricular block, or stress-induced atrial fibrillation. Notable adverse
      events included one case of bronchospasm and one case of heart failure
      exacerbation resulting in hospitalization. The most common symptoms in patients
      were dyspnoea (30%, n = 217), chest discomfort (27%, n = 200), and headache (15%,
      n = 111). There was minimal change between baseline and peak systolic and
      diastolic blood pressure in both patients and volunteers (P > 0.05). A blunted
      heart rate response to regadenoson was noted in patients with body mass index
      (BMI) >= 30 kg/m(2) (P < 0.001), and diabetes (P = 0.001). CONCLUSIONS:
      Regadenoson CMR is well tolerated and can be performed safely with few adverse
      events.

PMID- 24451180
TI  - Echocardiographic reference ranges for normal cardiac chamber size: results from
      the NORRE study.
AB  - AIMS: Availability of normative reference values for cardiac chamber quantitation
      is a prerequisite for accurate clinical application of echocardiography. In this
      study, we report normal reference ranges for cardiac chambers size obtained in a
      large group of healthy volunteers accounting for gender and age.
      Echocardiographic data were acquired using state-of-the-art cardiac ultrasound
      equipment following chamber quantitation protocols approved by the European
      Association of Cardiovascular Imaging. METHODS: A total of 734 (mean age: 45.8 +/
      13.3 years) healthy volunteers (320 men and 414 women) were enrolled at 22
      collaborating institutions of the Normal Reference Ranges for Echocardiography
      (NORRE) study. A comprehensive echocardiographic examination was performed on all
      subjects following pre-defined protocols. There were no gender differences in age
      or cholesterol levels. Compared with men, women had significantly smaller body
      surface areas, and lower blood pressure. Quality of echocardiographic data sets
      was good to excellent in the majority of patients. Upper and lower reference
      limits were higher in men than in women. The reference values varied with age.
      These age-related changes persisted for most parameters after normalization for
      the body surface area. CONCLUSION: The NORRE study provides useful two
      dimensional echocardiographic reference ranges for cardiac chamber
      quantification. These data highlight the need for body size normalization that
      should be performed together with age-and gender-specific assessment for the most
      echocardiographic parameters.

PMID- 24451182
TI  - Anaesthesia for orphan disease: combined spinal-epidural anaesthesia in a patient
      with Friedreich's ataxia.

PMID- 24451181
TI  - Genome resolved analysis of a premature infant gut microbial community reveals a
      Varibaculum cambriense genome and a shift towards fermentation-based metabolism
      during the third week of life.
AB  - BACKGROUND: The premature infant gut has low individual but high inter-individual
      microbial diversity compared with adults. Based on prior 16S rRNA gene surveys,
      many species from this environment are expected to be similar to those previously
      detected in the human microbiota. However, the level of genomic novelty and
      metabolic variation of strains found in the infant gut remains relatively
      unexplored. RESULTS: To study the stability and function of early microbial
      colonizers of the premature infant gut, nine stool samples were taken during the
      third week of life of a premature male infant delivered via Caesarean section.
      Metagenomic sequences were assembled and binned into near-complete and partial
      genomes, enabling strain-level genomic analysis of the microbial community.We
      reconstructed eleven near-complete and six partial bacterial genomes
      representative of the key members of the microbial community. Twelve of these
      genomes share >90% putative ortholog amino acid identity with reference genomes.
      Manual curation of the assembly of one particularly novel genome resulted in the
      first essentially complete genome sequence (in three pieces, the order of which
      could not be determined due to a repeat) for Varibaculum cambriense (strain
      Dora), a medically relevant species that has been implicated in abscess
      formation.During the period studied, the microbial community undergoes a
      compositional shift, in which obligate anaerobes (fermenters) overtake
      Escherichia coli as the most abundant species. Other species remain stable,
      probably due to their ability to either respire anaerobically or grow by
      fermentation, and their capacity to tolerate fluctuating levels of oxygen.
      Metabolic predictions for V. cambriense suggest that, like other members of the
      microbial community, this organism is able to process various sugar substrates
      and make use of multiple different electron acceptors during anaerobic
      respiration. Genome comparisons within the family Actinomycetaceae reveal
      important differences related to respiratory metabolism and motility.
      CONCLUSIONS: Genome-based analysis provided direct insight into strain-specific
      potential for anaerobic respiration and yielded the first genome for the genus
      Varibaculum. Importantly, comparison of these de novo assembled genomes with
      closely related isolate genomes supported the accuracy of the metagenomic
      methodology. Over a one-week period, the early gut microbial community
      transitioned to a community with a higher representation of obligate anaerobes,
      emphasizing both taxonomic and metabolic instability during colonization.

PMID- 24451183
TI  - The relationship between marital and parental status and the risk of dementia.
AB  - BACKGROUND: This study examines the association between marital and parental
      status and their individual and combined effect on risk of dementia diseases in a
      population-based longitudinal study while controlling for a range of potential
      confounders, including social networks and exposure to stressful negative life
      events. METHODS: A total of 1,609 participants without dementia, aged 65 years
      and over, were followed for an average period of 8.6 years (SD = 4.8). During
      follow-up, 354 participants were diagnosed with dementia. Cox regression was used
      to investigate the effect of marital and parental status on risk of dementia.
      RESULTS: In univariate Cox regression models (adjusted for age as time scale),
      widowed (hazard ratio (HR) 1.42, 95% confidence interval (CI) = 1.13-1.78), and
      not having children (HR 1.54, 95% CI = 1.15-2.06) were significantly associated
      with incident dementia. In multivariate analyses that included simultaneously
      marital and parental status and covariates that were found to be significant in
      univariate models (p < 0.10), the HR was 1.30 (95% CI = 1.01-1.66) for widowed,
      and 1.51 (95% CI = 1.08-2.10) for those not having children. Finally, a group of
      four combined factors was constructed: married parents (reference), married
      without children, widowed parents, and widowed without children. The combined
      effect revealed a 1.3 times higher risk (95% CI = 1.03-1.76) of dementia in widow
      parents, and a 2.2 times higher risk (95% CI = 1.36-3.60) in widowed persons
      without children, in relation to married parents. No significant difference was
      observed for those being married and without children. CONCLUSIONS: Our findings
      suggest that marital- and parental status are important risk factors for
      developing dementia, with especially increased risk in those being both widowed
      and without children.

PMID- 24451184
TI  - Water-mediated electrochemical nano-writing on thin ceria films.
AB  - Bias dependent mechanisms of irreversible cathodic and anodic processes on a pure
      CeO2 film are studied using modified atomic force microscopy (AFM). For a
      moderate positive bias applied to the AFM tip an irreversible electrochemical
      reduction reaction is found, associated with significant local volume expansion.
      By changing the experimental conditions we are able to deduce the possible role
      of water in this process. Simultaneous detection of tip height and current allows
      the onset of conductivity and the electrochemical charge transfer process to be
      separated, further elucidating the reaction mechanism. The standard
      anodic/cathodic behavior is recovered in the high bias regime, where a sizable
      transport current flows between the tip and the film. These studies give insight
      into the mechanisms of the tip-induced electrochemical reactions as mediated by
      electronic currents, and into the role of water in these processes, as well as
      providing a different approach for electrochemical nano-writing. 

PMID- 24451185
TI  - Gastrointestinal hormonal responses on GPR119 activation in lean and diseased
      rodent models of type 2 diabetes.
AB  - BACKGROUND: G protein-coupled receptor 119 (GPR119) has emerged as a potential
      target for the treatment of type 2 diabetes (T2D) and tool compounds have been
      critical in the evaluation of GPR119 functions. METHODS: We synthesised a novel
      small-molecule GPR119 agonist, PSN-GPR119, to study GPR119 signalling activities
      in cells overexpressing GPR119. We measured GPR119-stimulated peptide hormone
      release from intestinal loops and oral glucose tolerance in vivo from lean
      (C57BL/6J mouse or Sprague-Dawley (SD) rat) and diabetic (ob/ob mouse or ZDF rat)
      models. To evaluate the direct effects of GPR119 agonism on gastrointestinal (GI)
      tissue, we measured vectorial ion transport (measured as ISC; short-circuit
      current) across rodent GI mucosae and from normal human colon specimens. RESULTS:
      GPR119 activation by PSN-GPR119 increased cAMP accumulation in hGPR119
      overexpressing HEK293 cells (EC50, 5.5 nM), stimulated glucagon-like peptide 1
      (GLP-1) release from GLUTag cells (EC50, 75 nM) and insulin release from HIT-15
      cells (EC50, 90 nM). In vivo, PSN-GPR119 improved glucose tolerance by ~50% in
      lean mice or rats and ~60% in the diabetic ob/ob mouse or ZDF rat models. Luminal
      addition of PSN-GPR119 to isolated loops of lean rat small intestine stimulated
      GLP-1, glucose insulinotropic peptide (GIP) and peptide YY (PYY) release under
      basal (5 mM) and high glucose (25 mM) conditions. Activation of GPR119 also
      reduced intestinal ion transport. Apical or basolateral PSN-GPR119 addition (1
      MUM) to lean or T2D rodent colon mucosae reduced ISC levels via PYY-mediated Y1
      receptor agonism. The GPR119 response was glucose sensitive and was abolished by
      Y1 receptor antagonism. Similarly, in human colon, mucosa PSN-GPR119 acted via a
      Y1-specific mechanism. CONCLUSIONS: Our results show that functional GPR119
      responses are similar in lean and diabetic rodent, and human colon; that GPR119
      stimulation can result in glucose lowering through release of intestinal peptide
      hormones and that PSN-GPR119 is a useful tool compound for future studies.

PMID- 24451187
TI  - Gallstone disease in severely obese children participating in a lifestyle
      intervention program: incidence and risk factors.
AB  - INTRODUCTION: Cholelithiasis is increasingly encountered in childhood and
      adolescence due to the rise in obesity. As in adults, weight loss is presumed to
      be an important risk factor for cholelithiasis in children, but this has not been
      studied. METHODS: In a prospective observational cohort study we evaluated the
      presence of gallstones in 288 severely obese children and adolescents (mean age
      14.1+/-2.4 years, body mass index (BMI) z-score 3.39+/-0.37) before and after
      participating in a 6-month lifestyle intervention program. RESULTS: During the
      lifestyle intervention, 17/288 children (5.9%) developed gallstones. Gallstones
      were only observed in those losing >10% of initial body weight and the prevalence
      was highest in those losing >25% of weight. In multivariate analysis change in
      BMI z-score (odds ratio (OR) 3.26 (per 0.5 s.d. decrease); 95% CI:1.60-6.65) and
      baseline BMI z-score (OR 2.32 (per 0.5 s.d.); 95% CI: 1.16-4.70) were
      independently correlated with the development of gallstones. Sex, family history,
      OAC use, puberty and biochemistry were not predictive in this cohort. During post
      treatment follow-up (range 0.4-7.8 years) cholecystectomy was performed in 22% of
      those with cholelithiasis. No serious complications due to gallstones occurred.
      CONCLUSION: The risk of developing gallstones in obese children and adolescents
      during a lifestyle intervention is limited and mainly related to the degree of
      weight loss and initial body weight.

PMID- 24451186
TI  - Early atherogenesis and visceral fat in obese adolescents.
AB  - BACKGROUND/OBJECTIVES: Little information is available as to the cause of
      increased thickening of the intima-media of the carotid artery (cIMT) in the
      pediatric population. Therefore, cIMT was compared in obese adolescents and
      normal-weight controls, and associations between cIMT and lipid and non-lipid
      cardiovascular risk factors were assessed. SUBJECTS/METHODS: Subjects included 61
      obese non-diabetic male and female volunteers aged 12-18 years inclusive with a
      body mass index (BMI) >95th percentile for age and 2-h blood glucose <200 mg dl(
      1) matched to 25 normal-weight control volunteers with normal glucose levels.
      Each subject underwent a 2-h glucose tolerance test and measurement of hemoglobin
      A1c, ultrasensitive C-reactive protein, fasting insulin, blood lipids, visceral,
      subcutaneous abdominal and hepatic fat, and cIMT. RESULTS: Maximum cIMT was
      0.647+/-0.075 mm in the obese subjects versus 0.579+/-0.027 mm in normal-weight
      controls (P<0.001). There was no difference in maximum cIMT between male and
      female subjects. There were significant correlations between maximum cIMT and BMI
      z-score, 2-h glucose, fasting insulin, homeostasis model assessment (HOMA), total
      low-density lipoprotein (LDL) cholesterol, very LDL cholesterol, high-density
      lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, triglycerides,
      remnant lipoprotein cholesterol, intermediate-density lipoprotein cholesterol,
      lipoprotein(a), apoprotein B100, abdominal subcutaneous fat volume, visceral fat
      volume and hepatic phase difference. On multiple regression analysis, visceral
      fat was the most significant predictor of maximum cIMT. Two-hour blood glucose,
      HOMA and systolic blood pressure were also significant predictors of maximum
      cIMT. CONCLUSIONS: cIMT was increased in the obese adolescents compared with the
      normal-weight-matched controls. Visceral fat was a key predictor of arterial wall
      thickening in these subjects. The results suggest that the focus of
      cardiovascular disease prevention in the adolescent obese should be visceral
      obesity, and not blood lipids or lipid subclasses.

PMID- 24451188
TI  - Editorial: a synthetic approach to comparative cognition.

PMID- 24451189
TI  - Identification and biochemical characterization of halisulfate 3 and suvanine as
      novel inhibitors of hepatitis C virus NS3 helicase from a marine sponge.
AB  - Hepatitis C virus (HCV) is an important etiological agent that is responsible for
      the development of chronic hepatitis, liver cirrhosis, and hepatocellular
      carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for
      novel drug development due to its essential role in viral replication. In this
      study, we identified halisulfate 3 (hal3) and suvanine as novel NS3 helicase
      inhibitors, with IC50 values of 4 and 3 uM, respectively, from a marine sponge by
      screening extracts of marine organisms. Both hal3 and suvanine inhibited the
      ATPase, RNA binding, and serine protease activities of NS3 helicase with IC50
      values of 8, 8, and 14 uM, and 7, 3, and 34 uM, respectively. However, the dengue
      virus (DENV) NS3 helicase, which shares a catalytic core (consisting mainly of
      ATPase and RNA binding sites) with HCV NS3 helicase, was not inhibited by hal3
      and suvanine, even at concentrations of 100 uM. Therefore, we conclude that hal3
      and suvanine specifically inhibit HCV NS3 helicase via an interaction with an
      allosteric site in NS3 rather than binding to the catalytic core. This led to the
      inhibition of all NS3 activities, presumably by inducing conformational changes. 

PMID- 24451190
TI  - Alkaloids from the mangrove-derived actinomycete Jishengella endophytica 161111.
AB  - A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along
      with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2),
      (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde
      (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6
      carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1
      c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1
      c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-beta
      carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H
      indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13),
      were isolated and identified from the fermentation broth of an endophytic
      actinomycetes, Jishengella endophytica 161111. The new structure 1 and the
      absolute configurations of 2-6 were determined by spectroscopic methods, J-based
      configuration analysis (JBCA) method, lactone sector rule, and electronic
      circular dichroism (ECD) calculations. Compounds 8-11 were active against the
      influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of
      38.3(+/-1.2)/25.0(+/-3.6)/39.7(+/-5.6)/45.9(+/-2.1) MUg/mL and 3.0/16.1/3.1/11.4,
      respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(+/
      1.7) MUg/mL and 32.2, respectively. The results showed that compound 9 could be a
      promising new hit for anti-H1N1 drugs. The absolute configurations of 2-5, 13C
      nuclear magnetic resonance (NMR) data and the specific rotations of 3-6 were also
      reported here for the first time.

PMID- 24451191
TI  - Hyaluromycin, a new hyaluronidase inhibitor of polyketide origin from marine
      Streptomyces sp.
AB  - Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was
      isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase
      inhibitor on the basis of HAase activity screening. The structure of 1 was
      elucidated through the interpretation of NMR data for the compound and its 3"-O
      methyl derivative in combination with an incorporation experiment with [1,2
      13C2]acetate. The compound's absolute configuration was determined by the
      comparison of its circular dichroism (CD) spectrum with those of other
      rubromycins. Hyaluromycin (1) consists of a gamma-rubromycin core structure
      possessing a 2-amino-3-hydroxycyclopent-2-enone (C5N) unit as an amide
      substituent of the carboxyl function; both structural units have been reported
      only from actinomycetes. Hyaluromycin (1) displayed approximately 25-fold more
      potent hyaluronidase inhibitory activity against hyaluronidase than did
      glycyrrhizin, a known inhibitor of plant origin. 

PMID- 24451192
TI  - Analysis of the toxicity and histopathology induced by the oral administration of
      Pseudanabaena galeata and Geitlerinema splendidum (cyanobacteria) extracts to
      mice.
AB  - Cyanobacteria are common members of the freshwater microbiota in lakes and
      drinking water reservoirs, and are responsible for several cases of human
      intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are
      examples of the toxic species that are very frequently found in reservoirs in Sao
      Paulo, which is the most densely populated area in Brazil. In the search for
      toxic strains collected from water reservoirs and maintained in the
      Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil,
      the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt
      3223 were analyzed by planar chromatography, which indicated the absence of
      cyanotoxins. Animal tests were then carried out, and both extracts were found to
      induce toxic effects in mice when administered intraperitoneally. The present
      study aimed to investigate whether the oral ingestion of the above mentioned
      cyanobacteria extracts would also induce toxic effects in mice. Necropsy and
      histopathological studies were conducted using tissue samples from the animals,
      which were euthanized one week after the administration of the extracts. The AE
      of P. galeata did not cause death but did induce transient symptoms, including
      eyebrow ptosis, straub tail, and pain. The euthanized animals presented
      hemorrhage in the liver, whereas the histological analysis showed disorganization
      of the hepatic parenchyma, necrosis, hyperemia, and proximity of the
      centrilobular vein in the liver. In addition, alterations in the convoluted
      tubules of the kidneys were observed, and the lungs were unaffected. The AE of G.
      splendidum caused only one death, and induced transient symptoms, such as
      dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized
      mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic
      focuses, alveolar collapse, and granulomatous foci. The liver presented
      hemorrhagic and enlarged sinusoids, hyperemia, proximity of the centrilobular
      vein, and disorganization of the hepatic parenchyma. Some areas also exhibited an
      inflammatory infiltrate and calcified tissue inside blood vessels. Necrosis and
      rupture of the convoluted tubule cells were observed in the kidneys. Further
      analysis of the both extracts indicated the lack of hemolytic activity, and the
      presence of two unknown anti-AChE substances in the AE of G. splendidum. Thus, P.
      galeata and G. splendidum are producers of novel toxins that affect mammals when
      administered orally. 

PMID- 24451194
TI  - Apoptogenic metabolites in fractions of the Benthic diatom Cocconeis scutellum
      parva.
AB  - Benthic diatoms of the genus Cocconeis contain a specific apoptogenic activity.
      It triggers a fast destruction of the androgenic gland in the early post-larval
      life of the marine shrimp Hippolyte inermis, leading to the generation of small
      females. Previous in vitro investigations demonstrated that crude extracts of
      these diatoms specifically activate a dose-dependent apoptotic process in human
      cancer cells (BT20 breast carcinoma) but not in human normal lymphocytes. Here, a
      bioassay-guided fractionation has been performed to detect the apoptogenic
      compound(s). Various HPLC separation systems were needed to isolate the active
      fractions, since the apoptogenic metabolite is highly active, present in low
      amounts and is masked by abundant but non-active cellular compounds. The activity
      is due to at least two compounds characterized by different polarities, a
      hydrophilic and a lipophilic fraction. We purified the lipophilic fraction, which
      led to the characterization of an active sub-fraction containing a highly
      lipophilic compound, whose molecular structure has not yet been identified, but
      is under investigation. The results point to the possible medical uses of the
      active compound. Once the molecular structure has been identified, the study and
      modulation of apoptotic processes in various types of cells will be possible. 

PMID- 24451193
TI  - Marine natural products with P-glycoprotein inhibitor properties.
AB  - P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC)
      transporters superfamily that has clinical relevance due to its role in drug
      metabolism and multi-drug resistance (MDR) in several human pathogens and
      diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases,
      epilepsy and other disorders. This review article aims to summarize the research
      findings on the marine natural products with P-glycoprotein inhibitor properties.
      Natural compounds that modulate P-gp offer great possibilities for semi-synthetic
      modification to create new drugs and are valuable research tools to understand
      the function of complex ABC transporters. 

PMID- 24451195
TI  - Different resource allocation strategies result from selection for litter size at
      weaning in rabbit does.
AB  - This study examined the effect of long-term selection of a maternal rabbit line,
      solely for a reproductive criterion, on the ability of female rabbits to deal
      with constrained environmental conditions. Female rabbits from generations 16 and
      36 (n=72 and 79, respectively) of a line founded and selected to increase litter
      size at weaning were compared simultaneously. Female rabbits were subjected to
      normal (NC), nutritional (NF) or heat (HC) challenging conditions from 1st to 3rd
      parturition. Animals in NC and NF were housed at normal room temperatures (18
      degrees C to 25 degrees C) and respectively fed with control (11.6 MJ digestible
      energy (DE)/kg dry matter (DM), 126 g digestible protein (DP)/kg DM, and 168 g of
      ADF/kg DM) or low-energy fibrous diets (9.1 MJ DE/kg DM, 104 g DP/kg DM and 266 g
      ADF/kg DM), whereas those housed in HC were subjected to high room temperatures
      (25 degrees C to 35 degrees C) and the control diet. The litter size was lower
      for female rabbits housed in both NF and HC environments, but the extent and
      timing where this reduction took place differed between generations. In
      challenging conditions (NF and HC), the average reduction in the reproductive
      performance of female rabbits from generation 16, compared with NC, was -2.26
      (P<0.05) and -0.51 kits born alive at 2nd and 3rd parturition, respectively.
      However, under these challenging conditions, the reproductive performance of
      female rabbits from generation 36 was less affected at 2nd parturition (-1.25
      kits born alive), but showed a greater reduction at the 3rd parturition (-3.53
      kits born alive; P<0.05) compared with NC. The results also showed differences
      between generations in digestible energy intake, milk yield and accretion, and
      use of body reserves throughout lactation in NC, HC and NF, which together
      indicate that there were different resource allocation strategies in the animals
      from the different generations. Selection to increase litter size at weaning led
      to increased reproductive robustness at the onset of an environmental constraint,
      but failure to sustain the reproductive liability when the challenge was
      maintained in the long term. This response could be directly related to the short
      term environmental fluctuations (less severe) that frequently occur in the
      environment where this line has been selected.

PMID- 24451197
TI  - GraphProt: modeling binding preferences of RNA-binding proteins.
AB  - We present GraphProt, a computational framework for learning sequence- and
      structure-binding preferences of RNA-binding proteins (RBPs) from high-throughput
      experimental data. We benchmark GraphProt, demonstrating that the modeled binding
      preferences conform to the literature, and showcase the biological relevance and
      two applications of GraphProt models. First, estimated binding affinities
      correlate with experimental measurements. Second, predicted Ago2 targets display
      higher levels of expression upon Ago2 knockdown, whereas control targets do not.
      Computational binding models, such as those provided by GraphProt, are essential
      for predicting RBP binding sites and affinities in all tissues. GraphProt is
      freely available at http://www.bioinf.uni-freiburg.de/Software/GraphProt.

PMID- 24451198
TI  - Dilated cardiomyopathy due to a phospholamban duplication.
AB  - Dilated cardiomyopathy is characterised by dilation and impaired systolic
      function. We present the case of a child with dilated cardiomyopathy caused by a
      624 kb duplication of 6q22.31, which includes the phospholamban gene. The patient
      also has failure to thrive and developmental delay due to complex cytogenetic
      abnormalities including a 5p15 deletion associated with Cri du Chat and an 11p15
      duplication associated with Russell-Silver syndrome. 

PMID- 24451199
TI  - Positron emission tomography/computed tomography and biomarkers for early
      treatment response evaluation in metastatic colon cancer.
AB  - BACKGROUND: Treatment options for metastatic colon cancer (mCC) are widening. We
      prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission
      tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of
      metalloproteinases-1 (TIMP-1), carcinoembryonic antigen (CEA), and liberated
      domain I of urokinase plasminogen activator receptor (uPAR(I)) for early
      assessment of treatment response in mCC patients. METHODS: Thirty-three mCC
      patients scheduled for first-line chemotherapy with capecitabine and oxaliplatin
      (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before
      treatment, after one and four treatment series. Morphological and metabolic
      response was independently assessed according to Response Evaluation Criteria in
      Solid Tumors and European Organization for Research and Treatment of Cancer PET
      criteria. Plasma TIMP-1, plasma uPAR(I), and serum CEA were determined. RESULTS:
      Metabolic response after one treatment course predicted the ability of CAPOX and
      bevacizumab to induce morphological response after four treatment series with a
      sensitivity of 80%, specificity of 69%, and odds ratio of 13.9 (95% confidence
      interval [CI] 1.9; 182). Early metabolically stable or progressive disease was
      associated with shorter progression-free survival (hazard ratio [HR] = 3.2 [CI
      1.3; 7.8]). Biomarker levels at early evaluation were associated with shorter OS
      (TIMP-1 per unit increase on a log-2-transformed ng/mL scale: HR = 2.6 [CI 1.4;
      4.9]; uPAR(I) per 25 fmol/mL increase: HR = 1.5 [CI 1.1; 2.1]). CONCLUSION: This
      monocentric study demonstrated predictive value of early metabolic PET response
      and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and
      bevacizumab. Results support investigation of PET/CT, TIMP-1, and uPAR(I) guided
      early treatment adaptation in mCC.

PMID- 24451200
TI  - Tissue-specific pioneer factors associate with androgen receptor cistromes and
      transcription programs.
AB  - Androgen receptor (AR) binds male sex steroids and mediates physiological
      androgen actions in target tissues. ChIP-seq analyses of AR-binding events in
      murine prostate, kidney and epididymis show that in vivo AR cistromes and their
      respective androgen-dependent transcription programs are highly tissue specific
      mediating distinct biological pathways. This high order of tissue specificity is
      achieved by the use of exclusive collaborating factors in the three androgen
      responsive tissues. We find two novel collaborating factors for AR signaling in
      vivo--Hnf4alpha (hepatocyte nuclear factor 4alpha) in mouse kidney and AP-2alpha
      (activating enhancer binding protein 2alpha) in mouse epididymis--that define
      tissue-specific AR recruitment. In mouse prostate, FoxA1 serves for the same
      purpose. FoxA1, Hnf4alpha and AP-2alpha motifs are over-represented within unique
      AR-binding loci, and the cistromes of these factors show substantial overlap with
      AR-binding events distinct to each tissue type. These licensing or pioneering
      factors are constitutively bound to chromatin and guide AR to specific genomic
      loci upon hormone exposure. Collectively, liganded receptor and its DNA-response
      elements are required but not sufficient for establishment of tissue-specific
      transcription programs.

PMID- 24451201
TI  - Community differentiation of the cutaneous microbiota in psoriasis.
AB  - BACKGROUND: Psoriasis is a common chronic inflammatory disease of the skin. We
      sought to characterize and compare the cutaneous microbiota of psoriatic lesions
      (lesion group), unaffected contralateral skin from psoriatic patients (unaffected
      group), and similar skin loci in matched healthy controls (control group) in
      order to discern patterns that govern skin colonization and their relationship to
      clinical diagnosis. RESULTS: Using high-throughput 16S rRNA gene sequencing, we
      assayed the cutaneous bacterial communities of 51 matched triplets and
      characterized these samples using community data analysis techniques. Intragroup
      Unifrac beta diversity revealed increasing diversity from control to unaffected
      to lesion specimens. Likewise, principal coordinates analysis (PCoA) revealed
      separation of the lesion samples from unaffected and control along the first
      axis, suggesting that psoriasis is a major contributor to the observed diversity.
      The taxonomic richness and evenness decreased in both lesion and unaffected
      communities compared to control. These differences are explained by the combined
      increased abundance of the four major skin-associated genera (Corynebacterium,
      Propionibacterium, Staphylococcus, and Streptococcus), which present a
      potentially useful predictor for clinical skin type. Psoriasis samples also
      showed significant univariate decreases in relative abundances and strong
      classification performance of Cupriavidus, Flavisolibacter, Methylobacterium, and
      Schlegelella genera versus controls. The cutaneous microbiota separated into two
      distinct clusters, which we call cutaneotypes: (1) Proteobacteria-associated
      microbiota, and (2) Firmicutes-associated and Actinobacteria-associated
      microbiota. Cutaneotype 2 is enriched in lesion specimens compared to control
      (odds ratio 3.52 (95% CI 1.44 to 8.98), P <0.01). CONCLUSIONS: Our results
      indicate that psoriasis induces physiological changes both at the lesion site and
      at the systemic level, which select for specific differential microbiota among
      the assayed clinical skin types. These differences in microbial community
      structure in psoriasis patients are potentially of pathophysiologic and
      diagnostic significance.

PMID- 24451202
TI  - Role of thickness and intercalated water in the facile reduction of graphene
      oxide employing camera flash.
AB  - Graphene oxide (GO) is a potential precursor for the bulk production of graphene
      as the synthetic route is simple and cost-effective. Typically, reduction of GO
      is a time-consuming process and involves either toxic/hazardous reducing agents
      or high temperature treatment. Herein, we report the role of intercalated water
      and thickness of GO films towards the reduction of GO employing simple camera
      flash. A fast, simple and single camera flash instantaneously causes the
      deoxygenation reaction of GO without employing hazardous/toxic chemical
      reductants at room temperature. Successful reduction of GO employing camera flash
      has been verified via XRD, Raman and UV-vis spectroscopic analyses. Flash-reduced
      graphene shows a relatively high conductivity value of 740 S m(-1) with a C/O
      ratio of around 9.5. Intercalated water molecules facilitate the reduction by
      electron-hole pair formation. It has also been found that the intercalated water
      facilitates the reduction of GO up to a certain film thickness. However, the
      intensity of light passing through to the backside of a too thick film decreases
      significantly, causing incomplete reduction.

PMID- 24451203
TI  - Metagenomics reveals sediment microbial community response to Deepwater Horizon
      oil spill.
AB  - The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input
      of ~4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is
      unaccounted for, with unknown environmental consequences. Here we investigated
      the impact of oil deposition on microbial communities in surface sediments
      collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun
      metagenomic sequencing of 14 of these samples and mineralization experiments
      using (14)C-labeled model substrates. The 16S rRNA gene data indicated that the
      most heavily oil-impacted sediments were enriched in an uncultured
      Gammaproteobacterium and a Colwellia species, both of which were highly similar
      to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in
      structuring the microbial community were nitrogen and hydrocarbons. Annotation of
      unassembled metagenomic data revealed the most abundant hydrocarbon degradation
      pathway encoded genes involved in degrading aliphatic and simple aromatics via
      butane monooxygenase. The activity of key hydrocarbon degradation pathways by
      sediment microbes was confirmed by determining the mineralization of (14)C
      labeled model substrates in the following order: propylene glycol, dodecane,
      toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed
      an increase in abundance of genes involved in denitrification pathways in samples
      that exceeded the Environmental Protection Agency (EPA)'s benchmarks for
      polycyclic aromatic hydrocarbons (PAHs) compared with those that did not.
      Importantly, these data demonstrate that the indigenous sediment microbiota
      contributed an important ecosystem service for remediation of oil in the Gulf.
      However, PAHs were more recalcitrant to degradation, and their persistence could
      have deleterious impacts on the sediment ecosystem. 

PMID- 24451204
TI  - A new biofilm-associated colicin with increased efficiency against biofilm
      bacteria.
AB  - Formation of bacterial biofilm communities leads to profound physiological
      modifications and increased physical and metabolic exchanges between bacteria. It
      was previously shown that bioactive molecules produced within the biofilm
      environment contribute to bacterial interactions. Here we describe new pore
      forming colicin R, specifically produced in biofilms formed by the natural
      isolate Escherichia coli ROAR029 but that cannot be detected under planktonic
      culture conditions. We demonstrate that an increased SOS stress response within
      mature biofilms induces SOS-dependent colicin R expression. We provide evidence
      that colicin R displays increased activity against E. coli strains that have a
      reduced lipopolysaccharide length, such as the pathogenic enteroaggregative E.
      coli LF82 clinical isolate, therefore pointing to lipopolysaccharide size as an
      important determinant for resistance to colicins. We show that colicin R toxicity
      toward E. coli LF82 is increased under biofilm conditions compared with
      planktonic susceptibility and that release of colicin R confers a strong
      competitive advantage in mixed biofilms by rapidly outcompeting sensitive
      neighboring bacteria. This work identifies the first biofilm-associated colicin
      that preferentially targets biofilm bacteria. Furthermore, it indicates that the
      study of antagonistic molecules produced in biofilm and multispecies contexts
      could reveal unsuspected, ecologically relevant bacterial interactions
      influencing population dynamics in natural environments. 

PMID- 24451205
TI  - Single-cell enabled comparative genomics of a deep ocean SAR11 bathytype.
AB  - Bacterioplankton of the SAR11 clade are the most abundant microorganisms in
      marine systems, usually representing 25% or more of the total bacterial cells in
      seawater worldwide. SAR11 is divided into subclades with distinct spatiotemporal
      distributions (ecotypes), some of which appear to be specific to deep water. Here
      we examine the genomic basis for deep ocean distribution of one SAR11 bathytype
      (depth-specific ecotype), subclade Ic. Four single-cell Ic genomes, with
      estimated completeness of 55%-86%, were isolated from 770 m at station ALOHA and
      compared with eight SAR11 surface genomes and metagenomic datasets. Subclade Ic
      genomes dominated metagenomic fragment recruitment below the euphotic zone. They
      had similar COG distributions, high local synteny and shared a large number (69%)
      of orthologous clusters with SAR11 surface genomes, yet were distinct at the 16S
      rRNA gene and amino-acid level, and formed a separate, monophyletic group in
      phylogenetic trees. Subclade Ic genomes were enriched in genes associated with
      membrane/cell wall/envelope biosynthesis and showed evidence of unique phage
      defenses. The majority of subclade Ic-specfic genes were hypothetical, and some
      were highly abundant in deep ocean metagenomic data, potentially masking
      mechanisms for niche differentiation. However, the evidence suggests these
      organisms have a similar metabolism to their surface counterparts, and that
      subclade Ic adaptations to the deep ocean do not involve large variations in gene
      content, but rather more subtle differences previously observed deep ocean
      genomic data, like preferential amino-acid substitutions, larger coding regions
      among SAR11 clade orthologs, larger intergenic regions and larger estimated
      average genome size.

PMID- 24451206
TI  - Succession of cable bacteria and electric currents in marine sediment.
AB  - Filamentous Desulfobulbaceae have been reported to conduct electrons over
      centimetre-long distances, thereby coupling oxygen reduction at the surface of
      marine sediment to sulphide oxidation in sub-surface layers. To understand how
      these 'cable bacteria' establish and sustain electric conductivity, we followed a
      population for 53 days after exposing sulphidic sediment with initially no
      detectable filaments to oxygen. After 10 days, cable bacteria and electric
      currents were established throughout the top 15 mm of the sediment, and after 21
      days the filament density peaked with a total length of 2 km cm(-2). Cells
      elongated and divided at all depths with doubling times over the first 10 days of
      <20 h. Active, oriented movement must have occurred to explain the separation of
      O2 and H2S by 15 mm. Filament diameters varied from 0.4-1.7 MUm, with a general
      increase over time and depth, and yet they shared 16S rRNA sequence identity of
      >98%. Comparison of the increase in biovolume and electric current density
      suggested high cellular growth efficiency. While the vertical expansion of
      filaments continued over time and reached 30 mm, the electric current density and
      biomass declined after 13 and 21 days, respectively. This might reflect a
      breakdown of short filaments as their solid sulphide sources became depleted in
      the top layers of the anoxic zone. In conclusion, cable bacteria combine rapid
      and efficient growth with oriented movement to establish and exploit the
      spatially separated half-reactions of sulphide oxidation and oxygen consumption.

PMID- 24451208
TI  - Links between plant and fungal communities across a deforestation chronosequence
      in the Amazon rainforest.
AB  - Understanding the interactions among microbial communities, plant communities and
      soil properties following deforestation could provide insights into the long-term
      effects of land-use change on ecosystem functions, and may help identify
      approaches that promote the recovery of degraded sites. We combined high
      throughput sequencing of fungal rDNA and molecular barcoding of plant roots to
      estimate fungal and plant community composition in soil sampled across a
      chronosequence of deforestation. We found significant effects of land-use change
      on fungal community composition, which was more closely correlated to plant
      community composition than to changes in soil properties or geographic distance,
      providing evidence for strong links between above- and below-ground communities
      in tropical forests. 

PMID- 24451207
TI  - Evolutionary analysis of a streamlined lineage of surface ocean Roseobacters.
AB  - The vast majority of surface ocean bacteria are uncultivated. Compared with their
      cultured relatives, they frequently exhibit a streamlined genome, reduced G+C
      content and distinct gene repertoire. These genomic traits are relevant to
      environmental adaptation, and have generally been thought to become fixed in
      marine bacterial populations through selection. Using single-cell genomics, we
      sequenced four uncultivated cells affiliated with the ecologically relevant
      Roseobacter clade and used a composition-heterogeneous Bayesian phylogenomic
      model to resolve these single-cell genomes into a new clade. This lineage has no
      representatives in culture, yet accounts for ~35% of Roseobacters in some surface
      ocean waters. Analyses of multiple genomic traits, including genome size, G+C
      content and percentage of noncoding DNA, suggest that these single cells are
      representative of oceanic Roseobacters but divergent from isolates. Population
      genetic analyses showed that substitution of physicochemically dissimilar amino
      acids and replacement of G+C-rich to G+C-poor codons are accelerated in the
      uncultivated clade, processes that are explained equally well by genetic drift as
      by the more frequently invoked explanation of natural selection. The relative
      importance of drift vs selection in this clade, and perhaps in other marine
      bacterial clades with streamlined G+C-poor genomes, remains unresolved until more
      evidence is accumulated. 

PMID- 24451209
TI  - The quest for a unified view of bacterial land colonization.
AB  - Exploring molecular mechanisms underlying bacterial water-to-land transition
      represents a critical start toward a better understanding of the functioning and
      stability of the terrestrial ecosystems. Here, we perform comprehensive analyses
      based on a large variety of bacteria by integrating taxonomic, phylogenetic and
      metagenomic data, in the quest for a unified view that elucidates genomic,
      evolutionary and ecological dynamics of the marine progenitors in adapting to
      nonaquatic environments. We hypothesize that bacterial land colonization is
      dominated by a single-gene sweep, that is, the emergence of dnaE2 derived from an
      early duplication event of the primordial dnaE, followed by a series of niche
      specific genomic adaptations, including GC content increase, intensive horizontal
      gene transfer and constant genome expansion. In addition, early bacterial
      radiation may be stimulated by an explosion of land-borne hosts (for example,
      plants and animals) after initial land colonization events. 

PMID- 24451210
TI  - Lateral transfer of eukaryotic ribosomal RNA genes: an emerging concern for
      molecular ecology of microbial eukaryotes.
AB  - Ribosomal RNA (rRNA) genes are widely utilized in depicting organismal diversity
      and distribution in a wide range of environments. Although a few cases of lateral
      transfer of rRNA genes between closely related prokaryotes have been reported, it
      remains to be reported from eukaryotes. Here, we report the first case of lateral
      transfer of eukaryotic rRNA genes. Two distinct sequences of the 18S rRNA gene
      were detected from a clonal culture of the stramenopile, Ciliophrys infusionum.
      One was clearly derived from Ciliophrys, but the other gene originated from a
      perkinsid alveolate. Genome-walking analyses revealed that this alveolate-type
      rRNA gene is immediately adjacent to two protein-coding genes (ubc12 and usp39),
      and the origin of both genes was shown to be a stramenopile (that is, Ciliophrys)
      in our phylogenetic analyses. These findings indicate that the alveolate-type
      rRNA gene is encoded on the Ciliophrys genome and that eukaryotic rRNA genes can
      be transferred laterally. 

PMID- 24451212
TI  - Relationship between use of labor pain medications and delayed onset of
      lactation.
AB  - BACKGROUND: Despite estimates that 83% of mothers in the United States receive
      labor pain medications, little research has been done on how use of these
      medications affect onset of lactation. OBJECTIVE: To investigate whether use of
      labor pain medications is associated with delayed onset of lactation (DOL).
      METHODS: We analyzed data from the 2005-2007 Infant Feeding Practices Study II, a
      longitudinal study of women from late pregnancy through the entire first year
      after birth (n = 2366). In multivariable logistic regression analyses, we
      assessed the relationship between mothers' use of labor pain medication/method
      and DOL (milk coming in > 3 days after delivery). RESULTS: Overall, 23.4% of
      women in our sample experienced DOL. Compared with women who delivered vaginally
      and received no labor pain medication, women who received labor pain medications
      had a higher odds of experiencing DOL: vaginal with spinal/epidural only (aOR
      2.05; 95% CI, 1.43-2.95), vaginal with spinal/epidural plus another medication
      (aOR 1.79; 95% CI, 1.16-2.76), vaginal with other labor pain medications only
      ([not spinal/epidural]; aOR 1.84; 95% CI, 1.14-2.98), planned cesarean section
      with spinal/epidural only (aOR 2.13; 95% CI, 1.39-3.27), planned cesarean with
      spinal/epidural plus another medication (aOR 2.67; 95% CI, 1.35-5.29), emergency
      cesarean with spinal/epidural only (aOR 2.17; 95% CI, 1.34-3.51), and emergency
      cesarean with spinal/epidural plus another medication (aOR 3.03; 95% CI, 1.77
      5.18). CONCLUSION: Mothers who received labor pain medications were more likely
      to report DOL, regardless of delivery method. This information could help inform
      clinical decisions regarding labor/delivery.

PMID- 24451213
TI  - PIPE-CLIP: a comprehensive online tool for CLIP-seq data analysis.
AB  - CLIP-seq is widely used to study genome-wide interactions between RNA-binding
      proteins and RNAs. However, there are few tools available to analyze CLIP-seq
      data, thus creating a bottleneck to the implementation of this methodology. Here,
      we present PIPE-CLIP, a Galaxy framework-based comprehensive online pipeline for
      reliable analysis of data generated by three types of CLIP-seq protocol: HITS
      CLIP, PAR-CLIP and iCLIP. PIPE-CLIP provides both data processing and statistical
      analysis to determine candidate cross-linking regions, which are comparable to
      those regions identified from the original studies or using existing
      computational tools. PIPE-CLIP is available at http://pipeclip.qbrc.org/.

PMID- 24451214
TI  - Analysis of tumor mitotic rate in thin metastatic melanomas compared with thin
      melanomas without metastasis using both the hematoxylin and eosin and anti
      phosphohistone 3 IHC stain.
AB  - Studies have suggested that elevated tumor mitotic rate (MR) is linked to overall
      survival in thin melanoma. Recently, promising data regarding anti-phosphohistone
      3 (pHH3) immunohistochemistry and its ability to aid in calculation of MR have
      emerged. The authors retrospectively analyzed original biopsies from 13 thin
      melanomas with positive sentinel node (SN) status and 16 thin melanomas with
      negative SN status. Both anti-pHH3 immunohistochemistry and the hematoxylin and
      eosin (H&E) stain were used to evaluate MR by 2 dermatopathologists blinded to SN
      status using the "hot spot" method. Intraclass coefficient values were attained
      to measure interobserver concordance and reliability of the pHH3 stain. By
      generating a receiver operating characteristic curve and analyzing the overall
      area under the curve, pHH3 was found to have good interobserver reliability. The
      relationship between MR and SN involvement was also evaluated, but this
      correlation was not statistically significant.

PMID- 24451215
TI  - Nodule developing over a tattoo: challenge. Cutaneous lymphoid hyperplasia
      (pseudolymphoma).

PMID- 24451217
TI  - Effects of methoxychlor and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1
      trichloroethane on human and rat 17alpha-hydroxylase/17,20-lyase activity.
AB  - Exposure to methoxychlor, an agricultural pesticide, has been associated with
      reduced testicular androgen secretion. However, methoxychlor is converted to 2,2
      bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) in the liver, which then acts
      as its biologically active metabolite. Both methoxychlor and HPTE have been
      credited with estrogenic properties and have a weak anti-androgenic activity.
      However, the exact mechanisms of steroidogenic enzyme inhibition remain to be
      clarified. In the present study, human and rat testis microsomes were employed to
      investigate the inhibitory activities of methoxychlor and HPTE on 17alpha
      hydroxylase/17,20-lyase (CYP17A1). The CYP17A1 enzyme is critical for androgen
      biosynthesis and catalyzes conversion of progesterone into androstenedione. The
      results demonstrated that HPTE directly inhibited human and rat CYP17A1
      activities, while methoxychlor had no effects on this enzyme activity even at a
      concentration of 100 MUM. The IC50 values of HPTE were 1.13+/-0.10 (human) and
      6.87+/-0.13 MUM (rat), respectively. When HPTE was incubated with rat immature
      Leydig cells, it also inhibited CYP17A1 activity with an IC50 value of 6.29+/-0.1
      MUM. Results of enzyme inhibition were supported by the observation that HPTE
      inhibited luteinizing hormone-stimulated 5alpha-androstane-3alpha,17beta-diol and
      testosterone secretion by immature Leydig cells with IC50 values of 6.61+/-0.03
      and 3.78+/-0.003 MUM, respectively. The mode of action of HPTE on CYP17A1
      activity was determined to be uncompetitive with the substrate progesterone. In
      conclusion, HPTE, the metabolite of MXC, directly inhibited human and rat testis
      CYP17A1 activities.

PMID- 24451218
TI  - UPLC-MS-based serum metabonomics for identifying acute liver injury biomarkers in
      Chinese miniature pigs.
AB  - Metabonomics has emerged as an important technology for exploring the underlying
      mechanisms of diseases and screening for biomarkers. In this investigation, to
      comprehensively assess metabolite changes in D-galactosamine (GalN)-induced liver
      injury in Chinese miniature pigs and to increase our understanding of
      physiological changes in normal and pathological states, we used ultra
      performance liquid chromatography coupled with quadrupole time-of-flight mass
      spectrometry (UPLC-QTOF-MS) to analyze metabolites and identify biomarkers in
      serum. Blood samples were collected both from 18 h after GalN treatment group and
      control group pigs. We performed multivariate analyses on the metabolite profiles
      to identify potential biomarkers of acute liver injury, which were then confirmed
      by tandem MS. Based on "variable of importance in the project" (VIP) values and S
      plots, four groups of biomarkers were identified--namely conjugated bile acids,
      lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and fatty acid amides
      (FAAs)--that were present at significantly different levels in the control and
      GalN-induced groups. LPCs, PCs, and FAAs showed marked decreases in the GalN
      treated group, whereas conjugated bile acids in the treated group showed
      considerable increases. Taken together, our results suggested that obvious
      metabolic disturbances occur during acute liver injury, which provided novel
      insights into the molecular mechanism(s) of D-galactosamine (GalN)-induced liver
      injury, and will facilitate future research and management of liver injury.

PMID- 24451219
TI  - Electrolocation-based underwater obstacle avoidance using wide-field integration
      methods.
AB  - Weakly electric fish are capable of efficiently performing obstacle avoidance in
      dark and navigationally challenging aquatic environments using electrosensory
      information. This sensory modality enables extraction of relevant proximity
      information about surrounding obstacles by interpretation of perturbations
      induced to the fish's self-generated electric field. In this paper, reflexive
      obstacle avoidance is demonstrated by extracting relative proximity information
      using spatial decompositions of the perturbation signal, also called an electric
      image. Electrostatics equations were formulated for mathematically expressing
      electric images due to a straight tunnel to the electric field generated with a
      planar electro-sensor model. These equations were further used to design a wide
      field integration based static output feedback controller. The controller was
      implemented in quasi-static simulations for environments with complicated
      geometries modelled using finite element methods to demonstrate sense and avoid
      behaviours. The simulation results were confirmed by performing experiments using
      a computer operated gantry system in environments lined with either conductive or
      non-conductive objects acting as global stimuli to the field of the electro
      sensor. The proposed approach is computationally inexpensive and readily
      implementable, making underwater autonomous navigation in real-time feasible. 

PMID- 24451220
TI  - Menstrual cycle changes in women with inflammatory bowel disease: a study from
      the ocean state Crohn's and colitis area registry.
AB  - BACKGROUND: The effect of the inflammatory bowel diseases (IBD) on menstrual
      function is largely unknown. The aims of this study were to determine whether
      changes in menstrual function occur in the year before IBD diagnosis or in the
      initial years after diagnosis. METHODS: Women aged 18 years and older in the
      Ocean State Crohn's and Colitis Area Registry with at least 2 years of follow-up
      were eligible for this study. All patients were enrolled within 6 months of IBD
      diagnosis and followed prospectively. Menstrual cycle characteristics were
      retrospectively assessed. To assess for changes over time, general linear models
      for correlated data were used for continuous outcomes, and generalized estimating
      equations were used for discrete outcomes. RESULTS: One hundred twenty-one
      patients were studied. Twenty-five percent of patients experienced a change in
      cycle interval in the year before IBD diagnosis and 21% experienced a change in
      the duration of flow. Among women with dysmenorrhea, 40% experienced a change in
      the intensity of their menstrual pain and 31% experienced a change in its
      duration. Overall cycle regularity increased over time. Quality of life was
      significantly lower in women without regular cycles across all time points.
      CONCLUSIONS: Changes in menstrual function occur frequently in the year before
      IBD diagnosis; therefore, screening for menstrual irregularities should be
      considered in women with newly diagnosed IBD. Patients can be reassured that
      cycles typically become more regular over time.

PMID- 24451221
TI  - Validation of an internet-based cohort of inflammatory bowel disease (CCFA
      partners).
AB  - BACKGROUND: As traditional methods have become increasingly difficult, the
      Internet offers a mechanism for conducting survey research quickly and
      efficiently. However, the validity of this research depends on the ability of
      respondents to accurately report health status. We used a large Internet-based
      inflammatory bowel disease (IBD) cohort to validate self-reported IBD against
      physician reports. METHODS: Between June 22, 2012, and April 01, 2013, all
      participants of CCFA Partners (n = 6681) were invited to participate, and 450
      were selected by random stratified sampling. We sent physicians a survey to
      confirm IBD diagnosis and characteristics. We used descriptive statistics to
      compare data. RESULTS: A total of 4423 participants (66%) indicated interest. Of
      450 selected, 261 (58%) consented, and physician reports were obtained for 184
      (71%). Physicians confirmed IBD status in 178 (97%) and type in 171 (97% of
      confirmed). The matching between patient and physician reports for Crohn's
      disease (CD) was 82% for disease location, 89% for the presence of perianal
      disease, and 46% for disease behavior. For ulcerative colitis (UC), disease
      location matched 54% of the time. Physician reports confirmed the status of ever
      having bowel surgery for 97% of CD and 94% for UC and confirmed current pouch or
      ostomy in 84% of CD and 81% of UC. CONCLUSIONS: Self-reported IBD in CCFA
      Partners is highly accurate, and participants are willing to release medical
      records for research. Self-reported phenotypic characteristics were less valid.
      The validity of IBD diagnoses among the participants of CCFA Partners supports
      the use of this cohort for patient-centered outcome research.

PMID- 24451222
TI  - Implementable strategies and exploratory considerations to reduce costs
      associated with anti-TNF therapy in inflammatory bowel disease.
AB  - A health care system is needed where care is based on the best available evidence
      and is delivered reliably, efficiently, and less expensively (best care at lower
      cost). In gastroenterology, anti-tumor necrosis factor agents represent the most
      effective medical therapeutic option for patients with moderate-to-severe
      inflammatory bowel disease (IBD), but are very expensive and account for nearly a
      quarter of the cost of IBD care, representing a major area of present and future
      impact in direct health care costs. The ImproveCareNow Network, consisting of
      over 55 pediatric IBD centers, seeks ways to improve the value of care in IBD,
      curtailing unnecessary costs and promoting better health outcomes through
      systematic and incremental quality improvement initiatives. This report
      summarizes the key evidence to facilitate the cost-effective use of anti-tumor
      necrosis factor agents for patients with IBD. Our review outlines the scientific
      rationale for initiating cost-reducing measures in anti-tumor necrosis factor use
      and focuses on 3 implementable strategies and 4 exploratory considerations
      through practical clinical guidelines, as supported by existing evidence.
      Implementable strategies can be readily integrated into today's daily practice,
      whereas exploratory considerations can guide research to support future
      implementation.

PMID- 24451224
TI  - Maternal dietary omega-3 fatty acids and placental function.
AB  - The developing fetus requires substantial amounts of fatty acids to support rapid
      cellular growth and activity. Although the fatty acid composition delivered to
      the fetus is largely determined by maternal circulating levels, the placenta
      preferentially transfers physiologically important long-chain polyunsaturated
      fatty acids (LC-PUFAs), particularly omega-3 (n-3) PUFAs. Maternal dietary
      supplementation with n-3 PUFAs during pregnancy has been shown to increase
      gestation length, enhance fetal growth, and reduce the risk of pregnancy
      complications, although the precise mechanisms governing these effects remain
      uncertain. Omega-3 PUFAs are involved in several physiological pathways which
      could account for these effects, including anti-inflammatory, pro-resolving, and
      anti-oxidative pathways. Recent studies have shown that maternal dietary n-3 PUFA
      supplementation during rat pregnancy can reduce placental oxidative damage and
      increase placental levels of pro-resolving mediators, effects associated with
      enhanced fetal and placental growth. Because several placental disorders, such as
      intrauterine growth restriction, preeclampsia, and gestational diabetes mellitus,
      are associated with heightened placental inflammation and oxidative stress, there
      is considerable interest in the potential for dietary n-3 PUFAs as a therapeutic
      intervention for these disorders. In this study, we review the impact of dietary
      n-3 PUFAs on placental function, with particular focus on placental inflammation,
      inflammatory resolution, and oxidative stress. 

PMID- 24451223
TI  - Chromosome 22q11.21 microduplication in association with hypoplastic left heart
      syndrome with hypoplastic pulmonary arteries.
AB  - We describe a case of a baby girl born with hypoplastic left heart syndrome
      consisting of mitral atresia, aortic atresia, hypoplastic ascending aorta, and
      left ventricle. The pulmonary arteries were hypoplastic, measuring 3 mm.
      Fluorescence in situ hybridisation analysis demonstrated a microduplication of
      chromosome 22q11.2. Subsequent array comparative genomic hybridisation showed a
      gain of 2.3 Mb in one copy of chromosome 22q at band 22q11.21. The proband
      underwent a successful Norwood procedure with Sano shunt and subsequently
      underwent bi-directional Glenn shunt and Fontan procedure. This report highlights
      the association between hypoplastic left heart syndrome with hypoplastic
      pulmonary arteries and chromosome 22q11.21 microduplication. 

PMID- 24451225
TI  - Ubiquitous presence of paracetamol in human urine: sources and implications.
AB  - N-acetyl-4-aminophenol (acetaminophen/paracetamol, NA4AP) is one of the most
      commonly used over-the-counter analgesic and antipyretic drugs. Recent studies
      have reported anti-androgenic effects of NA4AP in vitro and possible associations
      between intrauterine exposure to NA4AP and the development of male reproductive
      disorders in humans. NA4AP is also a major metabolite of aniline (phenylamine),
      representing 75-86% of the aniline dose excreted in urine. Aniline is an
      important large-volume intermediate in several industrial processes. Besides
      individuals in various occupational settings with aniline exposure, the general
      population is also known to be ubiquitously exposed to aniline. In this article,
      we provide an overview of the recent literature concerning the intake of NA4AP
      during pregnancy and the possible anti-androgenic effects of NA4AP as well as
      literature concerning its known metabolic precursor aniline. We also present new
      research data, including the first human biomonitoring data on NA4AP excretion in
      urine, showing ubiquitous NA4AP body burdens in the general population at a wide
      range of concentrations. We found a small but significant impact of smoking on
      urinary NA4AP concentrations. We further present preliminary data on NA4AP
      excretion after therapeutic acetaminophen use, after aniline exposure in an
      occupational setting, and during a controlled fasting study (excluding oral
      exposure to both aniline and acetaminophen). Our findings indicate exposure to
      aniline (or aniline-releasing substances) as well as nutrition (next to the
      direct use of acetaminophen as medication) as possible sources of internal body
      burdens of NA4AP. 

PMID- 24451226
TI  - A stepwise likelihood ratio test procedure for rare variant selection in case
      control studies.
AB  - There is much recent interest in finding rare genetic variants associated with
      various diseases. Owing to the scarcity of rare mutations, single-variant
      analyses often lack power. To enable pooling of information across variants, we
      use a random effect formulation within a retrospective modeling framework that
      respects the retrospective data collecting mechanism of case-control studies.
      More concretely, we model the control allele frequencies of the variants as
      random effects, and the systematic differences between the case and control
      frequencies as fixed effects, resulting in a mixed model. The use of Poisson
      approximation and gamma-distributed random effects results in a generalized
      negative binomial distribution for the joint distribution of the control and case
      frequencies. Variants are selected by conducting stepwise likelihood ratio tests.
      The superiority of the proposed method over two existing variant selection
      methods is demonstrated in a simulation study. The effects of non-gamma random
      effects and correlated variants are also found to be not too detrimental in the
      simulation study. When the proposed procedure is applied to identify rare
      variants associated with obesity, it identifies one additional variant not picked
      up by existing methods.

PMID- 24451227
TI  - p.Arg75Gln, a CFTR variant involved in the risk of CFTR-related disorders?
AB  - c.224G>A, p.Arg75Gln (R75Q) presumably leads to an amino-acid change from
      arginine to glutamine in the membrane-spanning domain of the CFTR protein.
      Initially reported as a benign sequence variation, p.Arg75Gln was shown to be
      associated with a high risk of pancreatitis, a risk that was strikingly higher
      when p.Arg75Gln was combined with a SPINK1 variant. In addition, it was shown
      that p.Arg75Gln alters bicarbonate but not chloride conductance and that the
      mutation also induces exon 3 skipping. To investigate the role of p.Arg75Gln in
      idiopathic chronic pancreatitis (ICP), we performed genotyping of the CFTR gene
      in 880 patients with ICP, 198 patients with idiopathic bronchiectasis (IB), 74
      patients with classical cystic fibrosis (CF), 48 patients with congenital
      bilateral absence of the vas deferens (CBAVD) and 148 healthy controls.
      p.Arg75Gln variant was identified in 3.3% (29/880) of patients with ICP, 3.3%
      (9/272) patients with a pulmonary disease, 2.1% (1/48) of patients with CBAVD and
      4.7% (7/148) of healthy controls. It was frequently associated with the c.[1210
      12T[7];1408A>G] (T7-p.Val470) allele and this CFTR genetic background could not
      explain the putative pathogenicity of this variant. To assess whether CFTR and
      SPINK1 mutations are co-inherited in pancreatitis, we sequenced SPINK1 gene exon
      3 in the 46 patients who were previously identified to be heterozygous for
      p.Arg75Gln. Two SPINK1 pancreatitis-associated variants, p.Asn34Ser and
      p.Pro55Ser, were found in 6 patients: 4 of 29 (13.8%) patients with ICP (3
      p.Asn34Ser and 1 p.Pro55Ser), 1 of 7 (14.3%) healthy controls (p.Asn34Ser) and 1
      of 9 (11.1%) patients with IB (p.Pro55Ser). Our study does not confirm that the
      CFTR p.Arg75Gln mutation confers a significant risk of pancreatitis both when
      considered individually and with a concurrent SPINK1 mutation, suggesting the
      role of other genetic and environmental factors.

PMID- 24451229
TI  - Estimation of viral richness from shotgun metagenomes using a frequency count
      approach.
AB  - BACKGROUND: Viruses are important drivers of ecosystem functions, yet little is
      known about the vast majority of viruses. Viral shotgun metagenomics enables the
      investigation of broad ecological questions in phage communities. One ecological
      characteristic is species richness, which is the number of different species in a
      community. Viruses do not have a phylogenetic marker analogous to the bacterial
      16S rRNA gene with which to estimate richness, and so contig spectra are employed
      to measure the number of virus taxa in a given community. A contig spectrum is
      generated from a viral shotgun metagenome by assembling the random sequence reads
      into groups of sequences that overlap (contigs) and counting the number of
      sequences that group within each contig. Current tools available to analyze
      contig spectra to estimate phage richness are limited by relying on rank
      abundance data. RESULTS: We present statistical estimates of virus richness from
      contig spectra. The program CatchAll (http://www.northeastern.edu/catchall/) was
      used to analyze contig spectra in terms of frequency count data rather than rank
      abundance, thus enabling formal statistical analyses. Also, the influence of
      potentially spurious low-frequency counts on richness estimates was minimized by
      two methods, empirical and statistical. The results show greater estimates of
      viral richness than previous calculations in nearly all environments analyzed,
      including swine feces and reclaimed fresh water. CONCLUSIONS: CatchAll yielded
      consistent estimates of richness across viral metagenomes from the same or
      similar environments. Additionally, analysis of pooled viral metagenomes from
      different environments via mixed contig spectra resulted in greater richness
      estimates than those of the component metagenomes. Using CatchAll to analyze
      contig spectra will improve estimations of richness from viral shotgun
      metagenomes, particularly from large datasets, by providing statistical measures
      of richness.

PMID- 24451228
TI  - Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in
      the Japanese population based on comprehensive mutational analyses.
AB  - Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous
      neurodegenerative disorders characterized by progressive spasticity and pyramidal
      weakness of lower limbs. Because >30 causative genes have been identified,
      screening of multiple genes is required for establishing molecular diagnosis of
      individual patients with HSP. To elucidate molecular epidemiology of HSP in the
      Japanese population, we have conducted mutational analyses of 16 causative genes
      of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1,
      BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays,
      array-based comparative genomic hybridization and Sanger sequencing. The
      mutational analysis of 129 Japanese patients revealed 49 mutations in 46
      patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3%
      (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients,
      mutations were identified in 11.1% (7/63) of them. The present study elucidated
      the molecular epidemiology of HSP in the Japanese population and further
      broadened the mutational and clinical spectra of HSP. 

PMID- 24451230
TI  - Global developmental delay with sodium valproate-induced gingival hyperplasia.
AB  - Global developmental delay (GDD) refers to a disturbance in an individual child
      across one or more developmental domains, which include motor, cognition, daily
      activities, speech and language. The present case discusses a 5-year-old child
      with GDD associated with infantile spasms treated with sodium valproate. Delay in
      the widespread acquisition of skills, epilepsy and poor oral hygiene with
      gingival enlargement was the main concern to seek medical aid. This case is
      special as the child was suffering from GDD associated with sodium valproate
      induced gingival enlargement. 

PMID- 24451232
TI  - Bilateral axillary arterial obstruction.
AB  - A 74-year-old patient with longstanding diabetes mellitus and hypertension
      presented with obstruction in both axillary arteries. Although atherosclerotic
      obstructive disease would have been the most likely diagnosis in this patient,
      clinical findings were highly suggestive of extracranial giant-cell arteritis.
      Prompt treatment with systemic corticosteroids resulted in an excellent clinical
      response, avoiding the risks of endovascular or surgical intervention. 

PMID- 24451233
TI  - Plummer-Vinson syndrome with pectus carinatum mitral valve prolapsus and
      exotropia in an 18-year-old boy.
AB  - The Plummer-Vinson syndrome is a clinical syndrome characterised by dysphagia,
      web or webs in upper oesophagus and iron-deficiency anaemia. The syndrome is
      often seen in women of age 40-70 years and rarely in adolescents. Plummer-Vinson
      syndrome might be associated with malignancy, myeloproliferative disorder and
      autoimmune diseases including coeliac disease, rheumatoid arthritis and Sjogren
      syndrome. However, according to our literature search, there are no reports of
      such case associated with thorax deformity, cardiac pathology and ocular
      findings. We present a case of an 18-year-old boy with a rare presentation of
      this syndrome including pectus carinatum, exotropia and mitral valve prolapsus. 

PMID- 24451235
TI  - Enhancement of microbial motility due to speed-dependent nutrient absorption.
AB  - Marine microorganisms often reach high swimming speeds, either to take advantage
      of evanescent nutrient patches or to beat Brownian forces. Since this implies
      that a sizable part of their energetic budget must be allocated to motion, it is
      reasonable to assume that some fast-swimming microorganisms may increase their
      nutrient intake by increasing their speed v. We formulate a model to investigate
      this hypothesis and its consequences, finding the steady-state solutions and
      analyzing their stability. Surprisingly, we find that even modest increases in
      nutrient absorption may lead to a significant increase of the microbial speed. In
      fact, evaluations obtained using realistic parameter values for bacteria indicate
      that the speed increase due to the enhanced nutrient absorption may be quite
      large. 

PMID- 24451234
TI  - MutPred Splice: machine learning-based prediction of exonic variants that disrupt
      splicing.
AB  - We have developed a novel machine-learning approach, MutPred Splice, for the
      identification of coding region substitutions that disrupt pre-mRNA splicing.
      Applying MutPred Splice to human disease-causing exonic mutations suggests that
      16% of mutations causing inherited disease and 10 to 14% of somatic mutations in
      cancer may disrupt pre-mRNA splicing. For inherited disease, the main mechanism
      responsible for the splicing defect is splice site loss, whereas for cancer the
      predominant mechanism of splicing disruption is predicted to be exon skipping via
      loss of exonic splicing enhancers or gain of exonic splicing silencer elements.
      MutPred Splice is available at http://mutdb.org/mutpredsplice.

PMID- 24451236
TI  - Electronic states and wavefunctions of diatomic donor molecular ions in silicon:
      multi-valley envelope function theory.
AB  - Using the Burt-Foreman envelope function theory and effective mass approximation,
      we develop a theoretical model for an arbitrary number of interacting donor atoms
      embedded in silicon which reproduces the electronic energy spectrum with high
      computational efficiency, taking into account the effective mass anisotropy and
      the valley-orbit coupling. We show that the variation of the relative magnitudes
      of the electronic coupling between the donor atoms with respect to the valley
      orbit coupling as a function of the internuclear distance leads to different
      kinds of spatial interference patterns of the wavefunction. We also report on the
      impact of the orientation of the diatomic phosphorus donor molecular ion in the
      crystal lattice on the ionization energy and on the energy separation between the
      ground state and the lowest excited state.

PMID- 24451237
TI  - "Genetically Modified Lite" placates public but not activists: New technologies
      to manipulate plant genomes could help to overcome public concerns about GM
      crops.

PMID- 24451238
TI  - Marked effects of combined TPGS and PVA emulsifiers in the fabrication of
      etoposide-loaded PLGA-PEG nanoparticles: in vitro and in vivo evaluation.
AB  - The purpose of this study was to investigate the effect of d-alpha tocopheryl
      polyethylene glycol 1000 succinate (TPGS) alone or in combination with other
      emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles for in
      vivo applications. Nanoparticles were prepared by nanoprecipitation or single
      emulsion solvent evaporation method using TPGS alone or in combination with other
      surfactants. These nanoparticles were fully characterized by different
      techniques. For nanoprecipitation preparations, by adding 0.1% TPGS to polyvinyl
      alcohol in the aqueous phase, encapsulation efficiency markedly increased (up to
      82%); moreover, drug release was readily controlled up to 3 days. Regarding
      emulsion solvent evaporation method, the highest encapsulation efficiency was
      obtained for nanoparticles emulsified with polyvinyl alcohol or TPGS; however,
      the burst release was high. When the combination of TPGS and polyvinyl alcohol
      was applied a marked increase in encapsulation efficiency (~ 90%) was observed
      and the drug release was extended to more than one week. Pharmacokinetic
      measurements showed that the optimum formulation generated 14.4 times higher AUC
      and lasted 5.1 times longer when compared to free drug. Overall, using TPGS in
      combination with polyvinyl alcohol as an emulsifier in preparing etoposide loaded
      PLGA-PEG nanoparticles markedly increased the encapsulation efficiency, sustained
      drug release and resulted in nanoparticles with noticeable sustainable in vivo
      disposition.

PMID- 24451239
TI  - Polyethylene glycol-modified arachidyl chitosan-based nanoparticles for prolonged
      blood circulation of doxorubicin.
AB  - Doxorubicin (DOX)-loaded nanoparticles based on polyethylene glycol-conjugated
      chitosan oligosaccharide-arachidic acid (CSOAA-PEG) were explored for potential
      application to leukemia therapy. PEG was conjugated with CSOAA backbone via amide
      bond formation and the final product was verified by (1)H NMR analysis. Using the
      synthesized CSOAA-PEG, nanoparticles having characteristics of a 166-nm mean
      diameter, positive zeta potential, and spherical shape were produced for the
      delivery of DOX. The mean diameter of CSOAA-PEG nanoparticles in the serum
      solution (50% fetal bovine serum) remained relatively constant over 72 h as
      compared with CSOAA nanoparticles (changes of 20.92% and 223.16%, respectively).
      The sustained release pattern of DOX from CSOAA-PEG nanoparticles was displayed
      at physiological pH, and the release rate increased under the acidic pH
      conditions. The cytotoxicity of the CSOAA-PEG conjugate was negligible in human
      leukemia cells (K562) at the concentrations tested (~ 100 MUg/ml). The uptake
      rate of DOX from the nanoparticles by K562 cells was higher than that from the
      solution. Judging from the results of pharmacokinetic studies in rats, in vivo
      clearance rate of DOX from the CSOAA-PEG nanoparticle group was slower than other
      groups, subsequently extending the circulation period. The PEGylated CSOAA-based
      nanoparticles could represent an effective nano-sized delivery system for DOX
      which has been used for the treatment of blood malignancies.

PMID- 24451240
TI  - Does spinal MRI add incremental diagnostic value to MRI of the sacroiliac joints
      alone in patients with non-radiographic axial spondyloarthritis?
AB  - OBJECTIVE: To assess the incremental diagnostic value of spine MRI evaluated
      separately from and combined with sacroiliac joint (SIJ) MRI in non-radiographic
      axial spondyloarthritis (nr-axSpA) compared with SIJ MRI alone. METHODS: The
      study sample comprised two independent cohorts A/B of 130 consecutive patients
      aged <=50 years with back pain, newly referred to two university clinics, and 20
      healthy controls. Patients were classified according to clinical examination and
      pelvic radiographs as having nr-axSpA (n=50), ankylosing spondylitis (n=33), or
      non-specific back pain (n=47). Four readers assessed SIJ and spine MRI separately
      6 months apart, and 1-12 months later both scans simultaneously using
      standardised modules. Readers recorded presence/absence of SpA and their level of
      confidence in this conclusion on a 0-10 scale (0=definitely not; 10=definite). We
      analysed differences between SIJ MRI versus spine MRI alone, and SIJ MRI alone
      versus combined MRI, descriptively by the number/percentage of subjects according
      to the mean of four readers. RESULTS: In cohorts A/B, 15.8%/24.2% of patients
      with nr-axSpA having a negative SIJ MRI were reclassified as being positive for
      SpA by global evaluation of combined scans. However, 26.8%/11.4% of non-specific
      back pain controls and 17.5% of healthy volunteers with a negative SIJ MRI were
      falsely reclassified as having SpA by combined MRI. Low confidence in a diagnosis
      of SpA by SIJ MRI increased to high confidence by combined MRI in 6.6%/7.3% of
      patients with nr-axSpA. CONCLUSIONS: Combined spine and SIJ MRI added little
      incremental value compared with SIJ MRI alone for diagnosing patients with nr
      axSpA and enhancing confidence in this diagnosis.

PMID- 24451241
TI  - Hormone replacement therapy and mid-term implant survival following knee or hip
      arthroplasty for osteoarthritis: a population-based cohort study.
AB  - OBJECTIVES: Osteolysis and subsequent prosthesis loosening is the most common
      cause for revision following total knee arthroplasty (TKA) or total hip
      arthroplasty (THA). Hormone replacement therapy (HRT) could reduce osteolysis
      through its antiresorptive effects. We studied whether HRT use is associated with
      reduced revision rates in a community-based cohort of women undergoing TKA or THA
      for osteoarthritis. METHODS: Female participants in the General Practice Research
      Database undergoing a primary TKA or THA from 1986 to 2006 were included. We
      excluded patients aged <40 years at the date of primary, and those with a history
      of previous hip fracture or rheumatoid arthritis. Women with at least 6 months of
      HRT were identified as HRT users. We further explored the associations among HRT
      use of >=12 months, adherence (medication possession ratio) and cumulative use
      and revision risk. Cox models were fitted to model implant survival in years.
      Propensity score matching was used to control for confounding. RESULTS: We
      matched 2700 HRT users to 8100 non-users, observed for a median (IQR) of 3.3 (1.5
      6.1) years after TKA/THA. HR for HRT >=6 months was 0.62 (95% CI 0.41 to 0.94),
      whereas HR for >=12 months was 0.48 (0.29 to 0.78). Higher adherence and therapy
      duration were associated with further reductions in revision rates. Preoperative
      HRT appeared unrelated to implant survival. CONCLUSIONS: HRT use is associated
      with an almost 40% reduction in revision rates after a TKA/THA. These findings
      require replication in external cohorts and experimental studies.

PMID- 24451242
TI  - Two new phenolic compounds from the heartwood of Caesalpinia sappan L.
AB  - Two new phenolic compounds, epicaesalpin J and 7,10,11-trihydroxydracaenone, were
      isolated from the heartwood of Caesalpinia sappan L. Their structures were
      identified by spectroscopic analysis methods, such as 1D and 2D NMR, along with
      the high resolution mass spectral data. The NO inhibition activities of two new
      compounds and six known compounds were tested. 

PMID- 24451243
TI  - Influence of temperature on the enantioselectivity of koga tetraamines on amylose
      chiral stationary phases.
AB  - Enantioseparation is largely based on the formation of transitional complexes,
      the solvation species, the stationary phase configurations or the diastereomeric
      complexes formed by analytes and the chiral stationary phase. Temperature and the
      chemical nature and composition of the eluent play significant roles during that
      process. In this study; unique temperature-induced behaviors were observed during
      the enantioseparation of Koga tetraamines, also known as Koga bases, on
      polysaccharide chiral stationary phases, in which van't Hoff plots were acquired
      over a temperature range of 10  degrees C to 40  degrees C with 5  degrees C
      increments. Koga bases were eluted by a mixture of methanol and 2-propanol with
      0.03% triethylamine as a modifier. The van't Hoff plots are linear in the case of
      eluent containing equal volumes of methanol and 2-propanol. Increasing 2-propanol
      concentration from 50% to 85% in volume led to non-linear van't Hoff plots over
      the entire temperature range studied. Examination of the individual non-linear
      plots revealed two linear regions of 10  degrees C-20  degrees C and 20  degrees
      C-40  degrees C. Transition from one linear region to the other at 20  degrees C
      indicates alterations of chiral stationary phase conformation and/or
      enantioseparation mechanism as a result of temperature changes. 

PMID- 24451244
TI  - Physicochemical characteristics and anti-inflammatory activities of antrodan, a
      novel glycoprotein isolated from Antrodia cinnamomea mycelia.
AB  - Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of
      Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its
      bioproducts have been used to meet the market demand for natural fruiting bodies.
      AC exhibits anti-inflammatory, antitumor, antioxidant, and immunomodulatory
      effects. Previously, we isolated polysaccharide AC-2 from AC mycelia by means of
      alkali extraction with subsequent acid precipitation and found it had a
      pronounced anti-inflammatory effect. In this study, a novel polysaccharide named
      "antrodan" was obtained by further purification of AC-2 using Sepharose CL-6B
      column chromatography. Antrodan exhibited a molecular weight of 442 kD and
      contained a particularly high content of uronic acid (152.6+/-0.8 mg/g). The
      protein content was 71.0%, apparently, higher than the carbohydrate content
      (14.1%), and thus antrodan was characterized as a glycoprotein. Its total glucan
      content was 15.65%, in which beta-glucan (14.20%) was prominently higher than
      alpha-glucan (1.45%). Its FTIR confirmed the presence of beta-linkages between
      sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR
      spectrum showed that antrodan was a complex union of alpha- and beta-glucans,
      which had (1->4)-linked alpha-Glcp and (1->3)-linked beta-Glcp linkages to the
      carbohydrate chains via asparagine linked to protein site. Biologically, antrodan
      was confirmed to be totally non-detrimental to RAW 264.7 cell line even at dose
      as high as 400 MUg/mL. It showed potent suppressing effect on the
      lipopolysaccharide-induced inflammatory responses in RAW 264.7 cell line.
      Moreover, antrodan significantly reduced the nitrogen oxide production at doses
      as low as 18.75 MUg/mL.

PMID- 24451245
TI  - Wine by-products: phenolic characterization and antioxidant activity evaluation
      of grapes and grape pomaces from six different French grape varieties.
AB  - Grenache, Syrah, Carignan Noir, Mourvedre, Counoise and Alicante Bouchet grape
      seeds and skins, harvested in 2009 and 2010 in the Rhone valley area of France,
      and their respective pomaces remaining after vinification, were analyzed for
      their phenolic composition and antioxidant activity. The polyphenol content was
      quantified by HPLC and the Folin-Ciocalteu assay. The antioxidant potential was
      measured with four different assays: ORAC, FRAP, ABTS and DPPH. Seeds contained
      higher amounts of total polyphenols, up to 44.5 mg of gallic acid equivalent
      [GAE]/g dry weight in Alicante pomace, than skin extracts. The maximum total
      phenolic in skins was 31.6 mg GAE/g dry weight detected in 2010 Alicante pomace.
      Seeds also had the highest antioxidant capacity. HPLC analysis revealed that,
      despite the vinification process, pomaces still contained an appreciable amount
      of proanthocyanidins as well as several anthocyanin glycosides. Alicante and
      Syrah proved to be the varieties of most interest in terms of their potential
      development for nutraceutical purposes. 

PMID- 24451246
TI  - Characterization of a new sesquiterpene and antifungal activities of chemical
      constituents from Dryopteris fragrans (L.) Schott.
AB  - One new sesquiterpene and six known compounds were isolated from Dryopteris
      fragrans (L.) Schot. They were identified as 3-O-beta-D-glucopyranosylalbicanol-
      11-O-beta-D-glucopyranoside (1), dihydroconiferylalcohol (2), (E)-3-(4
      hydroxyphenyl)acrylic acid (3), esculetin (4), 5,7-dihydroxy-2
      hydroxymethylchromone (5), eriodictyol (6) and isoorientin (7) by UV, MS, 1D-NMR
      and 2D-NMR spectroscopy. The antifungal activities of the seven isolated
      compounds were screened. Compounds 2, 3, 4 and 5 showed obvious activities
      against Microsporum canis and Epidermophyton floccosum. 

PMID- 24451247
TI  - New natural diterpene-type abietane from Tetradenia riparia essential oil with
      cytotoxic and antioxidant activities.
AB  - Tetradenia riparia (Hochstetter) Codd belongs to the Lamiaceae family and it was
      introduced in Brazil as an exotic ornamental plant. A previous study showed its
      antimicrobial, acaricidal and analgesic activities. Two compounds were isolated
      from essential oil of T. riparia leaves and identified as 9beta,13beta-epoxy-7
      abietene (1), a new one, and 6,7-dehydroroyleanone (2), already reported for
      another plant. The structure of these compounds was determined by spectroscopic
      analysis and by comparison with literature data. The cytotoxic activities of the
      essential oil and compounds 1 and 2 were determined by a 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and by tumor cells MDA-MB
      435 (human breast carcinoma), HCT-8 (human colon), SF-295 (human nervous system)
      and HL-60 (human promyelocytic leukemia). The essential oil and compound 1 showed
      high cytotoxic potential of the cell lines SF-295 (78.06% and 94.80%,
      respectively), HCT-8 (85.00% and 86.54%, respectively) and MDA-MB-435 (59.48% and
      45.43%, respectively). Compound 2 had no cytotoxic activity. The antioxidant
      activity was determined by 2,2-diphenyl-1-picryl-hydrazyl (DPPH), beta-carotene
      linoleic acid system and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS) assays. The inhibitory concentration (IC50 in ug mL-1) for essential oil
      and compound 2 was, respectively 15.63 and 0.01 for DPPH; 130.1 and 109.6 for
      beta-carotene-linoleic acid and 1524 and 1024 for ABTS. Compound 1 had no
      antioxidant activity. By fractioning the oil, it was possible to identify two
      unpublished compounds: 1 with high cytotoxic potential and 2 with high
      antioxidant potential. 

PMID- 24451248
TI  - Saccharide substituted zinc phthalocyanines: optical properties, interaction with
      bovine serum albumin and near infrared fluorescence imaging for sentinel lymph
      nodes.
AB  - Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1
      (beta-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and
      [2,9(10), 16(17),23(24)-tetrakis((1-(beta-D-lactose-2-yl)-1H-1,2,3-triazol-4
      yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared
      fluorescence agents. Their interaction with bovine serum albumin was investigated
      by fluorescence and circular dichroism spectroscopy and isothermal titration
      calorimetry. Near infrared imaging for sentinel lymph nodes in vivo was performed
      using nude mice as models. Results show that saccharide- substituted zinc
      phthalocyanines have favourable water solubility, good optical stability and high
      emission ability in the near infrared region. The interaction of lactose
      substituted phthalocyanine with bovine serum albumin displays obvious differences
      to that of glucose- substituted phthalocyanine. Moreover, lactose-substituted
      phthalocyanine possesses obvious imaging effects for sentinel lymph nodes in
      vivo. 

PMID- 24451249
TI  - Synthesis of 4-methoxybenzoylhydrazones and evaluation of their antiglycation
      activity.
AB  - A series of 4-methoxybenzoylhydrazones 1-30 was synthesized and the structures of
      the synthetic derivatives elucidated by spectroscopic methods. The compounds
      showed a varying degree of antiglycation activity, with IC50 values ranging
      between 216.52 and 748.71 uM, when compared to a rutin standard (IC50=294.46+/
      1.50 uM). Compounds 1 (IC50=216.52+/-4.2 uM), 3 (IC50=289.58+/-2.64 uM), 6
      (IC50=227.75+/-0.53 uM), 7 (IC50=242.53+/-6.1) and 11 (IC50=287.79+/-1.59) all
      showed more activity that the standard, and these compounds have the potential to
      serve as possible leads for drugs to inhibit protein glycation in diabetic
      patients. A preliminary SAR study was performed.

PMID- 24451250
TI  - Crystal structures, vibrational spectra, and fungicidal activity of 1,5-diaryl-3
      oxypyrazoles.
AB  - The aryloxypyrazole structure is present in a number of bioactive molecules. Four
      1,5-diaryl-3-oxypyrazoles containing benzoyl (I), thiazolidinethione (II and III)
      or per-O-acetylated glucopyranosyl (IV) moieties were characterized by single
      crystal X-ray diffraction. Compounds I and II crystallize in a triclinic P-1
      system, whereas III and IV crystallize in an orthorhombic Pbca and a monoclinic
      P21 space groups, respectively. The dihedral angles between the two benzene rings
      of the pyrazole are 61.33 degrees  (I), 62.87 degrees  (II), 57.09 degrees  (III)
      and 70.25 degrees  (IV). The structures were stabilized by classical intra- (C
      H...S for II and III, C-H...O for IV) and intermolecular (C-H...O for I and IV) H
      bonds, as well as intermolecular C-H...pi stacking interactions. The theoretical
      FTIR results showed good agreement with the experimental data. Compounds IV, II
      and III showed moderate fungicidal activity against Sclerotinia sclerotiorum and
      Gibberella zeae. The structure-activity relationships were discussed. 

PMID- 24451251
TI  - Antibacterial and antioxidant activities of ursolic acid and derivatives.
AB  - Ursolic acid, an important bioactive compound, was isolated from ethanol extract
      of aerial parts of Sambucus australis. In order to develop bioactive ursolic acid
      derivatives, two semi-synthetic compounds were obtained through modification at C
      3. The antibacterial activity of the ursolic acid and its derivatives was
      investigated. The microdilution method was used for determination of the minimal
      inhibitory concentration (MIC), against twelve bacterial strains. The influence
      of ursolic acid and its derivatives on the susceptibility of some bacterial
      pathogens to the aminoglycosides antibiotics neomycin, amikacin, kanamycin and
      gentamicin was evaluated. The most representative synergistic effect was observed
      by 3beta-formyloxy-urs-12-en-28-oic acid at the concentration of 64 MUg/mL in
      combination with kanamycin against Escherichia coli (27), a multidrug-resistant
      clinical isolate from sputum, with reduction of MIC value from 128 MUg/mL to 8
      MUg/mL. Ursolic acid and its derivatives were examined for their radical
      scavenger activity using the DPPH assay, and showed significant activity. 

PMID- 24451252
TI  - EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall
      glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK
      signaling pathway.
AB  - Our previous studies showed that urinary Tamm-Horsfall glycoprotein (THP)
      potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the
      domain structure(s), signaling pathway and the intracellular events responsible
      for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from
      normal human urine. The human promyelocytic leukemia cell line HL-60 was induced
      to differentiate into PMNs by all-trans retinoid acid. Pretreatment with
      different MAPK and PI3K inhibitors was used to delineate signaling pathways in
      THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN
      phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human
      recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38
      MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP
      induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho
      family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further
      studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell
      phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974
      significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and
      ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF
      receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by
      activating Rho family and MAP kinase. 

PMID- 24451253
TI  - Synthesis and characterization of impurities of barnidipine hydrochloride, an
      antihypertensive drug substance.
AB  - Barnidipine hydrochloride is a long term dihydropyridine calcium channel blocker
      used for the treatment of hypertension. During the process development of
      barnidipine hydrochloride, four barnidipine impurities were detected by high
      performance liquid chromatography (HPLC) with an ordinary column (Agilent ZORBAX
      Eclipse XDB-C18, 150 mm*4.6 mm, 5 um). All these impurities were identified,
      synthesized, and subsequently characterized by their respective spectral data
      (MS, 1H-NMR, and 13C-NMR). The identification of these impurities should be
      useful for quality control in the manufacture of barnidipine.

PMID- 24451254
TI  - Molecular dynamics of neutral polymer bonding agent (NPBA) as revealed by solid
      state NMR spectroscopy.
AB  - Neutral polymer bonding agent (NPBA) is one of the most promising polymeric
      materials, widely used in nitrate ester plasticized polyether (NEPE) propellant
      as bonding agent. The structure and dynamics of NPBA under different conditions
      of temperatures and sample processing are comprehensively investigated by solid
      state NMR (SSNMR). The results indicate that both the main chain and side chain
      of NPBA are quite rigid below its glass transition temperature (Tg). In contrast,
      above the Tg, the main chain remains relatively immobilized, while the side
      chains become highly flexible, which presumably weakens the interaction between
      bonding agent and the binder or oxidant fillers and in turn destabilizes the high
      modulus layer formed around the oxidant fillers. In addition, no obvious
      variation is found for the microstructure of NPBA upon aging treatment or soaking
      with acetone. These experimental results provide useful insights for
      understanding the structural properties of NPBA and its interaction with other
      constituents of solid composite propellants under different processing and
      working conditions. 

PMID- 24451255
TI  - Comment on Gao, W., et al. "Efficient one-pot synthesis of 5-chloromethyl
      furfural (CMF) from carbohydrates in mild biphasic systems", Molecules 2013, 18,
      7675-7685.
AB  - In a recent paper entitled "Efficient One-Pot Synthesis of 5-Chloromethyl
      furfural (CMF) from Carbohydrates in Mild Biphasic Systems," published in
      Molecules [1], Gao and coworkers describe the use of a biphasic aq. HCl
      H3PO4/CHCl3 reagent for the preparation of CMF from various feedstocks. The
      maximum yield (46.8%) was obtained from fructose by reaction at 45  degrees C for
      20 h. While sucrose gave a similar yield, the same reaction with glucose and
      cellulose gave 7.3% and 7.8% yields, respectively. Remarkably, the same process
      applied to Kraft pulp and powdered wood samples gave between 16.0% and 31.4% CMF,
      based on sugar content. Looking to the Experimental section for insight into this
      unusual outcome, the statement, "the procedure of treating lignocellulose sample
      (Table 6) was almost the same as the carbohydrate, except adding the selected
      simple 1.0 mg each trial " [sic] appears, which is difficult to interpret.

PMID- 24451256
TI  - Correction: Gao, W., et al. Efficient One-Pot Synthesis of 5-Chloromethyl
      furfural (CMF) from Carbohydrates in Mild Biphasic Systems. Molecules 2013, 18,
      7675-7685.

PMID- 24451257
TI  - Molecules Best Paper Award 2014.

PMID- 24451258
TI  - Golgi complex-plasma membrane trafficking directed by an autonomous, tribasic
      Golgi export signal.
AB  - Although numerous linear motifs that direct protein trafficking within cells have
      been identified, there are few examples of linear sorting signals mediating
      directed export of membrane proteins from the Golgi complex to the plasma
      membrane. The reovirus fusion-associated small transmembrane proteins are simple,
      single-pass transmembrane proteins that traffic through the endoplasmic reticulum
      Golgi pathway to the plasma membrane, where they induce cell-cell membrane
      fusion. Here we show that a membrane-proximal, polybasic motif (PBM) in the
      cytosolic tail of p14 is essential for efficient export of p14 from the Golgi
      complex to the plasma membrane. Extensive mutagenic analysis reveals that the
      number, but not the identity or position, of basic residues present in the PBM
      dictates p14 export from the Golgi complex, with a minimum of three basic
      residues required for efficient Golgi export. Results further indicate that the
      tribasic motif does not affect plasma membrane retention of p14. Furthermore,
      introduction of the tribasic motif into a Golgi-localized, chimeric ERGIC-53
      protein directs export from the Golgi complex to the plasma membrane. The p14 PBM
      is the first example of an autonomous, tribasic signal required for Golgi export
      to the plasma membrane. 

PMID- 24451259
TI  - Borg5 is required for angiogenesis by regulating persistent directional migration
      of the cardiac microvascular endothelial cells.
AB  - The microvasculature is important for vertebrate organ development and
      homeostasis. However, the molecular mechanism of microvascular angiogenesis
      remains incompletely understood. Through studying Borg5 (Binder of the Rho GTPase
      5), which belongs to a family of poorly understood effector proteins of the Cdc42
      GTPase, we uncover a role for Borg5 in microvascular angiogenesis. Deletion of
      Borg5 in mice results in defects in retinal and cardiac microvasculature as well
      as heart development. Borg5 promotes angiogenesis by regulating persistent
      directional migration of the endothelial cells (ECs). In primary mouse cardiac
      ECs (MCECs), Borg5 associates with septins in the perinuclear region and
      colocalizes with actomyosin fibers. Both Borg5 deletion and septin 7 knockdown
      lead to a disruption of the perinuclear actomyosin and persistent directional
      migration. Our findings suggest that Borg5 and septin cytoskeleton spatially
      control actomyosin activity to ensure persistent directional migration of MCECs
      and efficient microvascular angiogenesis. Our studies reported here should offer
      a new avenue to further investigate the functions of Borg5, septin, and
      actomyosin in the microvasculature in the context of development and disease. 

PMID- 24451260
TI  - Transcriptional repression of hypoxia-inducible factor-1 (HIF-1) by the protein
      arginine methyltransferase PRMT1.
AB  - Hypoxia-inducible factors (HIF-1 and HIF-2) are essential mediators for the
      adaptive transcriptional response of cells and tissues to low-oxygen conditions.
      Under hypoxia or when cells are treated with various nonhypoxic stimuli, the
      active HIF-alpha subunits are mainly regulated through increased protein
      stabilization. For HIF-1alpha, it is clear that further transcriptional,
      translational, and posttranslational regulations are important for complete HIF-1
      activity. Novel evidence links hypoxia and HIF-1 to arginine methylation, an
      important protein modification. These studies suggest that arginine
      methyltransferases may be important for hypoxic responses. Protein arginine
      methyltransferase 1 (PRMT1), the predominant arginine methyltransferase, can act
      as a transcriptional activator or repressor by modifying a diverse set of
      substrates. In this work, we show that PRMT1 is a repressor of both HIF-1 and HIF
      2. The cellular depletion of PRMT1 by small interference RNA targeting leads to
      increased HIF transcriptional activity. This activation is the result of enhanced
      HIF-alpha subunit transcription, which allows increased HIF-alpha subunit
      availability. We provide evidence that PRMT1-dependent HIF-1alpha regulation is
      mediated through the activities of both specificity protein 1 (Sp1) and Sp3, two
      transcription factors known to control HIF-1alpha expression. This study
      therefore identifies PRMT1 as a novel regulator of HIF-1- and HIF-2-mediated
      responses. 

PMID- 24451261
TI  - The depletion of F1 subunit epsilon in yeast leads to an uncoupled respiratory
      phenotype that is rescued by mutations in the proton-translocating subunits of
      F0.
AB  - The central stalk of the ATP synthase is an elongated hetero-oligomeric structure
      providing a physical connection between the catalytic sites in F1 and the proton
      translocation channel in F0 for energy transduction between the two subdomains.
      The shape of the central stalk and relevance to energy coupling are essentially
      the same in ATP synthases from all forms of life, yet the protein composition of
      this domain changed during evolution of the mitochondrial enzyme from a two- to a
      three-subunit structure (gamma, delta, epsilon). Whereas the mitochondrial gamma-
      and delta-subunits are homologues of the bacterial central stalk proteins, the
      deliberate addition of subunit epsilon is poorly understood. Here we report that
      down-regulation of the gene (ATP15) encoding the epsilon-subunit rapidly leads to
      lethal F0-mediated proton leaks through the membrane because of the loss of
      stability of the ATP synthase. The epsilon-subunit is thus essential for
      oxidative phosphorylation. Moreover, mutations in F0 subunits a and c, which slow
      the proton translocation rate, are identified that prevent epsilon-deficient ATP
      synthases from dissipating the electrochemical potential. Cumulatively our data
      lead us to propose that the epsilon-subunit evolved to permit operation of the
      central stalk under the torque imposed at the normal speed of proton movement
      through mitochondrial F0.

PMID- 24451263
TI  - Aim44p regulates phosphorylation of Hof1p to promote contractile ring closure
      during cytokinesis in budding yeast.
AB  - Whereas actomyosin and septin ring organization and function in cytokinesis are
      thoroughly described, little is known regarding the mechanisms by which the
      actomyosin ring interacts with septins and associated proteins to coordinate cell
      division. Here we show that the protein product of YPL158C, Aim44p, undergoes
      septin-dependent recruitment to the site of cell division. Aim44p colocalizes
      with Myo1p, the type II myosin of the contractile ring, throughout most of the
      cell cycle. The Aim44p ring does not contract when the actomyosin ring closes.
      Instead, it forms a double ring that associates with septin rings on mother and
      daughter cells after cell separation. Deletion of AIM44 results in defects in
      contractile ring closure. Aim44p coimmunoprecipitates with Hof1p, a conserved F
      BAR protein that binds both septins and type II myosins and promotes contractile
      ring closure. Deletion of AIM44 results in a delay in Hof1p phosphorylation and
      altered Hof1p localization. Finally, overexpression of Dbf2p, a kinase that
      phosphorylates Hof1p and is required for relocalization of Hof1p from septin
      rings to the contractile ring and for Hof1p-triggered contractile ring closure,
      rescues the cytokinesis defect observed in aim44 cells. Our studies reveal a
      novel role for Aim44p in regulating contractile ring closure through effects on
      Hof1p. 

PMID- 24451262
TI  - NAADP and the two-pore channel protein 1 participate in the acrosome reaction in
      mammalian spermatozoa.
AB  - The functional relationship between the formation of hundreds of fusion pores
      during the acrosome reaction in spermatozoa and the mobilization of calcium from
      the acrosome has been determined only partially. Hence, the second messenger
      NAADP, promoting efflux of calcium from lysosome-like compartments and one of its
      potential molecular targets, the two-pore channel 1 (TPC1), were analyzed for its
      involvement in triggering the acrosome reaction using a TPCN1 gene-deficient
      mouse strain. The present study documents that TPC1 and NAADP-binding sites
      showed a colocalization at the acrosomal region and that treatment of spermatozoa
      with NAADP resulted in a loss of the acrosomal vesicle that showed typical
      properties described for TPCs: Registered responses were not detectable for its
      chemical analogue NADP and were blocked by the NAADP antagonist trans-Ned-19. In
      addition, two narrow bell-shaped dose-response curves were identified with maxima
      in either the nanomolar or low micromolar NAADP concentration range, where TPC1
      was found to be responsible for activating the low affinity pathway. Our finding
      that two convergent NAADP-dependent pathways are operative in driving acrosomal
      exocytosis supports the concept that both NAADP-gated cascades match local NAADP
      concentrations with the efflux of acrosomal calcium, thereby ensuring complete
      fusion of the large acrosomal vesicle. 

PMID- 24451264
TI  - Mitotic regulation of fungal cell-to-cell connectivity through septal pores
      involves the NIMA kinase.
AB  - Intercellular bridges are a conserved feature of multicellular organisms. In
      multicellular fungi, cells are connected directly via intercellular bridges
      called septal pores. Using Aspergillus nidulans, we demonstrate for the first
      time that septal pores are regulated to be opened during interphase but closed
      during mitosis. Septal pore-associated proteins display dynamic cell cycle
      regulated locations at mature septa. Of importance, the mitotic NIMA kinase
      locates to forming septa and surprisingly then remains at septa throughout
      interphase. However, during mitosis, when NIMA transiently locates to nuclei to
      promote mitosis, its levels at septa drop. A model is proposed in which NIMA
      helps keep septal pores open during interphase and then closed when it is removed
      from them during mitosis. In support of this hypothesis, NIMA inactivation is
      shown to promote interphase septal pore closing. Because NIMA triggers nuclear
      pore complex opening during mitosis, our findings suggest that common cell cycle
      regulatory mechanisms might control septal pores and nuclear pores such that they
      are opened and closed out of phase to each other during cell cycle progression.
      The study provides insights into how and why cytoplasmically connected
      Aspergillus cells maintain mitotic autonomy. 

PMID- 24451265
TI  - Characteristics of hospitals diverting ambulances in a California EMS system.
AB  - INTRODUCTION: While several reports discuss controversies regarding ambulance
      diversion from acute care hospitals and the mortality, financial, and resource
      effects, there is scant literature related to the effect of hospital
      characteristics. HYPOTHESIS/PROBLEM: The objective of this study was to describe
      specific paramedic receiving center characteristics that are associated with
      ambulance diversion rates in an Emergency Medical Services system. METHODS: A
      retrospective observational study design was used. The study was performed in a
      suburban EMS system with 27 paramedic receiving centers studied; one additional
      hospital present at the beginning of the study period (2000-2008) was excluded
      due to lack of recent data. Hospital-level and population-level characteristics
      were gathered, including diversion rate (hours on diversion/total hours open),
      for-profit status, number of specialty services (including trauma, burn,
      cardiovascular surgery, renal transplant services, cardiac catheterization
      capability [both interventional and diagnostic], and burn surgery), average
      inpatient bed occupancy rate (total patient days/licensed bed days), annual
      emergency department (ED) volume (patients per year), ED admission rate (percent
      of ED patients admitted), and percent of patients leaving without being seen.
      Demographic characteristics included percent of persons in each hospital's
      immediate census tract below the 100% and 200% poverty lines (each considered
      separately), and population density within the census tract. Bivariate and
      regression analyses were performed. RESULTS: Diversion rates for the 27 centers
      ranged from 0.3%-14.5% (median 4.5%). Average inpatient bed occupancy rate and
      presence of specialty services were correlated with an increase in diversion
      rate; occupancy rate showed a 0.08% increase in diversion hours per 1% increase
      in occupancy rate (95% CI, 0.01%-0.16%), and hospitals with specialty services
      had, on average, a 4.1% higher diversion rate than other hospitals (95% CI, 1.6%
      6.7%). Other characteristics did not show a statistically significant effect.
      When a regression was performed, only the presence of specialty services was
      related to the ambulance diversion rate. CONCLUSIONS: Hospitals in this study
      providing specialty services were more likely to have higher diversion rates.
      This may result in increased difficulty getting patients requiring specialty care
      to centers able to provide the needed level of service. Major limitations include
      the retrospective nature of the study, as well as reliance on multiple data
      systems.

PMID- 24451266
TI  - Biocompatibility and characterization of a Kolsterised((r)) medical grade cobalt
      chromium-molybdenum alloy.
AB  - High failure rates of cobalt-chromium-molybdenum (Co-Cr-Mo) metal-on-metal hip
      prosthesis were reported by various authors, probably due to the alloy's limited
      hardness and tribological properties. This thus caused the popularity of the
      alloy in metal-on-metal hip replacements to decrease due to its poor wear
      properties when compared with other systems such as ceramic-on-ceramic. S-phase
      surface engineering has become an industry standard when citing surface hardening
      of austenitic stainless steels. This hardening process allows the austenitic
      stainless steel to retain its corrosion resistance, while at the same time also
      improving its hardness and wear resistance. By coupling S-phase surface
      engineering, using the proprietary Kolsterising((r)) treatment from Bodycote
      Hardiff GmbH, that is currently being used mainly on stainless steel, with Co-Cr
      Mo alloys, an improvement in hardness and tribological characteristics is
      predicted. The objective of this paper is to analyze the biocompatibility of a
      Kolsterised((r)) Co-Cr-Mo alloy, and to characterize the material surface in
      order to show the advantages gained by using the Kolsterised((r)) material
      relative to the original untreated alloy, and other materials. This work has been
      performed on 3 fronts including; Material characterization, "In-vitro" corrosion
      testing, and Biological testing conforming to BS EN ISO 10993-18:2009 -
      Biological evaluation of medical devices. Using these techniques, the
      Kolsterised((r)) cobalt-chromium-molybdenum alloys were found to have good
      biocompatibility and an augmented corrosion resistance when compared with the
      untreated alloy. The Kolsterised((r)) samples also showed a 150% increase in
      surface hardness over the untreated material thus predicting better wear
      properties. 

PMID- 24451267
TI  - Landscape complexity influences route-memory formation in navigating pigeons.
AB  - Observations of the flight paths of pigeons navigating from familiar locations
      have shown that these birds are able to learn and subsequently follow habitual
      routes home. It has been suggested that navigation along these routes is based on
      the recognition of memorized visual landmarks. Previous research has identified
      the effect of landmarks on flight path structure, and thus the locations of
      potentially salient sites. Pigeons have also been observed to be particularly
      attracted to strong linear features in the landscape, such as roads and rivers.
      However, a more general understanding of the specific characteristics of the
      landscape that facilitate route learning has remained out of reach. In this
      study, we identify landscape complexity as a key predictor of the fidelity to the
      habitual route, and thus conclude that pigeons form route memories most strongly
      in regions where the landscape complexity is neither too great nor too low. Our
      results imply that pigeons process their visual environment on a characteristic
      spatial scale while navigating and can explain the different degrees of success
      in reproducing route learning in different geographical locations. 

PMID- 24451268
TI  - HONEST to clarify association between home blood pressure and cardiovascular
      events under antihypertensive medication.

PMID- 24451269
TI  - Effect of olmesartan on blood pressure in patients with hypertension:
      specification on causality.

PMID- 24451270
TI  - CloVR-ITS: Automated internal transcribed spacer amplicon sequence analysis
      pipeline for the characterization of fungal microbiota.
AB  - BACKGROUND: Besides the development of comprehensive tools for high-throughput
      16S ribosomal RNA amplicon sequence analysis, there exists a growing need for
      protocols emphasizing alternative phylogenetic markers such as those representing
      eukaryotic organisms. RESULTS: Here we introduce CloVR-ITS, an automated pipeline
      for comparative analysis of internal transcribed spacer (ITS) pyrosequences
      amplified from metagenomic DNA isolates and representing fungal species. This
      pipeline performs a variety of steps similar to those commonly used for 16S rRNA
      amplicon sequence analysis, including preprocessing for quality, chimera
      detection, clustering of sequences into operational taxonomic units (OTUs),
      taxonomic assignment (at class, order, family, genus, and species levels) and
      statistical analysis of sample groups of interest based on user-provided
      information. Using ITS amplicon pyrosequencing data from a previous human gastric
      fluid study, we demonstrate the utility of CloVR-ITS for fungal microbiota
      analysis and provide runtime and cost examples, including analysis of extremely
      large datasets on the cloud. We show that the largest fractions of reads from the
      stomach fluid samples were assigned to Dothideomycetes, Saccharomycetes,
      Agaricomycetes and Sordariomycetes but that all samples were dominated by
      sequences that could not be taxonomically classified. Representatives of the
      Candida genus were identified in all samples, most notably C. quercitrusa, while
      sequence reads assigned to the Aspergillus genus were only identified in a subset
      of samples. CloVR-ITS is made available as a pre-installed, automated, and
      portable software pipeline for cloud-friendly execution as part of the CloVR
      virtual machine package (http://clovr.org). CONCLUSION: The CloVR-ITS pipeline
      provides fungal microbiota analysis that can be complementary to bacterial 16S
      rRNA and total metagenome sequence analysis allowing for more comprehensive
      studies of environmental and host-associated microbial communities.

PMID- 24451271
TI  - Study of the electronic and magnetic properties as a function of isoelectronic
      substitution in SmFe(1-x)RuxAsO0.85F0.15.
AB  - We have studied the electronic and magnetic properties of SmFe(1
      x)RuxAsO0.85F0.15 (x = 0, 0.05, 0.25, 0.33, 0.5) by high-resolution x-ray
      absorption and x-ray emission spectroscopy. The local Fe magnetic moment (MU)
      tends to decrease for a small Ru substitution, but it shows a clear increase with
      further substitution. It appears that impurity scattering prevails in reducing
      the MU with small Ru substitution due to an extended Ru d-band. A nanoscale phase
      separation, that decouples the FeAs layers from the spacer layers, drives the
      increase of MU at higher Ru substitution. The results provide important
      information on nanoscale phase separation due to isoelectronic substitution in
      the active layers of iron-based 1111-superconductors and its effect on the local
      magnetic properties.

PMID- 24451276
TI  - Comparative analysis of atypical spitz tumors with heterozygous versus homozygous
      9p21 deletions for clinical outcomes, histomorphology, BRAF mutation, and p16
      expression.
AB  - Studies have shown that atypical Spitz tumors (ASTs) with homozygous deletions in
      9p21 have worse prognosis than those without this finding. Conversely, numerous
      studies have shown that a range of other copy number aberrations including
      isolated 6q23 or 3p21 loss may be seen in ASTs without conferring higher risk for
      aggressive behavior. We studied 31 cases of ASTs with heterozygous 9p21 loss and
      hypothesize that heterozygous 9p21 loss in ASTs does not confer an increased risk
      for aggressive behavior. We compared clinical, histopathologic, and
      immunohistochemical features of 31 ASTs with heterozygous 9p21 deletions with 30
      ASTs with homozygous 9p21 deletions. No ASTs with heterozygous 9p21 deletions
      resulted in distant metastasis. Severe cytologic atypia, a predominance of
      epithelioid cytomorphology and increased dermal mitotic activity were more
      frequent in ASTs with homozygous deletions versus ASTs with heterozygous
      deletions (P=0.0003, 0.0004, and 0.042, respectively). Expression of p16 and
      mutated BRAF proteins was also evaluated in 17 conventional (nonspitzoid)
      melanomas with homozygous 9p21 loss and the 2 groups of ASTs. Expression of p16
      was retained in 67% of ASTs with heterozygous loss, whereas among ASTs with
      homozygous loss, 100% of cases had areas with complete loss of staining. Mutated
      BRAF protein expression was detected in 53% of conventional melanomas, in none of
      the ASTs with heterozygous loss, and in 1 AST with homozygous loss (P=0.0007
      between homozygous ASTs and the conventional melanomas). Coexisting BRAF mutation
      and 9p21 deletion was more common in conventional melanomas than in ASTs with
      heterozygous or homozygous 9p21 deletion. BRAF mutation was highly uncommon among
      the ASTs. 

PMID- 24451277
TI  - Diagnostic utility of targeted next-generation sequencing in problematic cases.
AB  - Targeted next-generation sequencing (NGS) provides predictive and prognostic
      information in the routine care of patients with cancer. However, with increasing
      knowledge of the biological basis of cancer, NGS of the same gene sets can also
      provide diagnostic information in challenging cases, on the basis of
      identification of both known and novel variants, including single-nucleotide
      variants, insertions and deletions, copy number alterations, and translocations.
      Here, we present 3 clinical cases in which targeted NGS of hybrid-capture
      enriched DNA from formalin-fixed, paraffin-embedded tumor samples provided unique
      and clinically important diagnostic and/or staging information in 3 different
      challenging clinical scenarios. In the first patient, NGS played a key role in
      both diagnosis and staging in a patient with multiple tumors of the same
      histologic type. The second case demonstrates the ability of NGS to clarify the
      tumor tissue type in a single mass involving multiple organs, and thereby guide
      appropriate chemotherapy. The third case illustrates that information regarding
      susceptibility to targeted therapeutics can also clarify the original histologic
      diagnosis. 

PMID- 24451278
TI  - Whipple made simple for surgical pathologists: orientation, dissection, and
      sampling of pancreaticoduodenectomy specimens for a more practical and accurate
      evaluation of pancreatic, distal common bile duct, and ampullary tumors.
AB  - Pancreaticoduodenectomy (PD) specimens present a challenge for surgical
      pathologists because of the relative rarity of these specimens, combined with the
      anatomic complexity. Here, we describe our experience on the orientation,
      dissection, and sampling of PD specimens for a more practical and accurate
      evaluation of pancreatic, distal common bile duct (CBD), and ampullary tumors.
      For orientation of PDs, identification of the "trapezoid," created by the
      vascular bed at the center, the pancreatic neck margin on the left, and the
      uncinate margin on the right, is of outmost importance in finding all the
      pertinent margins of the specimen including the CBD, which is located at the
      upper right edge of this trapezoid. After orientation, all the margins can be
      sampled. We submit the uncinate margin entirely as a perpendicular inked margin
      because this adipose tissue-rich area often reveals subtle satellite carcinomas
      that are grossly invisible, and, with this approach, the number of R1 resections
      has doubled in our experience. Then, to ensure proper identification of all lymph
      nodes (LNs), we utilize the orange-peeling approach, in which the soft tissue
      surrounding the pancreatic head is shaved off in 7 arbitrarily defined regions,
      which also serve as shaved samples of the so-called "peripancreatic soft tissue"
      that defines pT3 in the current American Joint Committee on Cancer TNM. With this
      approach, our LN count increased from 6 to 14 and LN positivity rate from 50% to
      73%. In addition, in 90% of pancreatic ductal adenocarcinomas there are grossly
      undetected microfoci of carcinoma. For determination of the primary site and the
      extent of the tumor, we believe bisectioning of the pancreatic head, instead of
      axial (transverse) slicing, is the most revealing approach. In addition,
      documentation of the findings in the duodenal surface of the ampulla is crucial
      for ampullary carcinomas and their recent site-specific categorization into 4
      categories. Therefore, we probe both the CBD and the pancreatic duct from distal
      to the ampulla and cut the pancreatic head to the ampulla at a plane that goes
      through both ducts. Then, we sample the bisected pancreatic head depending on the
      findings of the case. For example, for proper staging of ampullary carcinomas, it
      is imperative to take the sections perpendicular to the duodenal serosa at the
      "groove" area, as ampullary carcinomas often extend to this region. Amputative
      (axial) sectioning of the ampulla, although good for documentation of the peri
      Oddi spread of the intra-ampullary tumors, unfortunately disallows documentation
      of mucosal spread of the papilla of Vater tumors (those arising from the edge of
      the ampulla, where the ducts transition to duodenal mucosa and extending) into
      the neighboring duodenum. Axial sectioning also often fails to document tumor
      spread to the "groove" area. In conclusion, knowledge of the gross
      characteristics of the anatomic hallmarks is essential for proper dissection of
      PD specimens. The approach described above allows practical and accurate
      documentation and staging of pancreas, distal CBD, and ampullary cancers. 

PMID- 24451279
TI  - Appendiceal or cecal endometriosis with intestinal metaplasia: a potential mimic
      of appendiceal mucinous neoplasms.
AB  - Appendiceal or cecal endometriosis uncommonly presents diagnostic challenges, but
      rare cases with intestinal metaplasia can mimic mucinous tumors of the appendix.
      We describe 6 cases of appendiceal or cecal endometriosis with intestinal
      metaplasia that grossly and microscopically mimicked appendiceal mucinous tumors.
      The cases were characterized by marked mural hypertrophy and elastosis, with
      distortion of the appendix, and virtual obliteration of the lumen of the
      appendix. All cases had conventional endometriosis, together with varying amounts
      of endometriosis with intestinal-type epithelium. In 2 cases, scant or virtually
      no stroma around some mucin-filled glands made their recognition as endometriosis
      more difficult. None of the cases had dysplasia of the mucinous epithelium. All
      patients had benign follow-up (mean 3.6 y). Endometriosis with intestinal
      metaplasia is a rare phenomenon that, when it occurs in the appendix or cecum,
      may lead to misdiagnosis as a low-grade appendiceal mucinous neoplasm or mucinous
      carcinoma. 

PMID- 24451280
TI  - Molecular characterization of undifferentiated carcinoma associated with
      endometrioid carcinoma.
AB  - Uterine and ovarian undifferentiated carcinomas (UCs) are often associated with
      low-grade endometrioid carcinomas (EMCs) and are characterized by a solid growth
      pattern and a lack of appreciable features of differentiation. As compared with
      pure EMC, UC is highly malignant, and the molecular pathogenesis that leads to
      disease aggressiveness remains largely unknown. This study interrogates the
      molecular pathogenesis of UCs by comparing the molecular alterations between the
      UC and the EMC components. A total of 20 UCs were studied, 12 of which contained
      both UC and EMC components. Mutation analysis was performed for the genes
      commonly mutated in EMC, and immunohistochemistry was used to determine the
      expression pattern of beta-catenin and PTEN. Sequencing analysis revealed that
      UCs harbored somatic mutations in PIK3CA (50%), CTNNB1 (30%), TP53 (30%), FBXW7
      (20%), and PPP2R1A (20%). All somatic mutations detected in EMCs were also
      present in concurrent UCs. Moreover, additional somatic mutations were detected
      in the UC component in 5 (42%) cases with concurrent EMC and UC. Concordance of
      immunostaining pattern for beta-catenin and PTEN was recorded in all 12 matched
      EMCs and UCs, except 4 cases in which nuclear accumulation of beta-catenin
      staining was detected in one of the components but not in the other. Our findings
      support a clonal relationship between EMCs and their associated UCs. Additional
      molecular genetics alteration, including mutations of CTNNB1, PPP2R1A, and TP53,
      may contribute to tumor progression from EMC to UC. 

PMID- 24451287
TI  - Majorana fermions in T-shaped semiconductor nanostructures.
AB  - We investigate the Majorana fermions in a T-shaped semiconductor nanostructure
      with the Rashba spin-orbit coupling and a magnetic field in the proximity of an s
      wave superconductor. It is found that the properties of the low-energy modes
      (including the Majorana and near-zero-energy modes) at the ends of this system
      are similar to those in the Majorana nanowire. However, very distinct from the
      nanowire, one Majorana mode emerges at the intersection of the T-shaped structure
      when the number of the low-energy modes at each end N is odd, whereas neither
      Majorana nor near-zero-energy mode appears at the intersection for even N. We
      also discover that the intersection Majorana mode plays an important role in the
      transport through the above T-shaped nanostructure with each end connected with a
      normal lead. Due to the presence of the intersection mode, the deviation of the
      zero-bias conductance from the ideal value in the long-arm limit Ne2/h is more
      pronounced in the regime of odd N compared to the one of even N. Furthermore,
      when the magnetic field increases from the regime of odd N to the one of even N +
      1, the deviation from the ideal value tends to decrease. This behavior is also
      very distinct from that in a nanowire, where the deviation always tends to
      increase with the increase of magnetic field.

PMID- 24451290
TI  - Health economic evaluation of single-lead atrial pacing vs. dual-chamber pacing
      in sick sinus syndrome.
AB  - AIMS: The recent Danish Multicentre Randomized Trial on Single-Lead Atrial (AAIR)
      Pacing versus Dual-Chamber (DDDR) Pacing in Sick Sinus Syndrome (DANPACE)
      suggested DDDR pacing as standard care. However, previous findings supported the
      routine use of AAIR pacing. This study investigated the cost-effectiveness of
      DDDR pacing compared with AAIR pacing for sick sinus syndrome. METHODS AND
      RESULTS: A decision-analytical model based on patient-level data from three
      randomized trials was designed from the Danish healthcare system's perspective.
      The main outcomes were lifetime costs, quality-adjusted lifeyears (QALYs), and
      net monetary benefit. Quality-adjusted lifeyears were calculated by utilizing
      community-based preferences. Costs were calculated by utilizing the extensive
      data on resource consumption, from the DANPACE trial. Data were pooled and
      adjusted for baseline differences. Dual-chamber pacing was shown to be cost
      effective in all the analyses using a willingness-to-pay (WTP) threshold of
      L20,000/QALY, and most analyses using a WTP of L30,000/QALY. When pooling the
      data and adjusting for baseline differences, Monte Carlo simulations revealed a
      51-71% probability of DDDR pacing being cost-effective at a WTP of L20,000/QALY,
      and a 42-58% probability at a WTP of L30,000/QALY. Dual-chamber pacing was most
      likely to be cost-effective among elderly patients with comorbidity. The expected
      value of perfect information was low and initiation of additional publicly funded
      Danish trials was discouraged. CONCLUSION: Dual-chamber pacing is likely to be a
      cost-effective treatment for sick sinus syndrome patients.

PMID- 24451291
TI  - Awareness of indications for device therapy among a broad range of physicians: a
      survey study.
AB  - AIMS: Cardiac resynchronization therapy (CRT) and primary prophylactic
      implantable cardioverter-defibrillators (ICDs) are underutilized in heart failure
      (HF). This may originate from an unawareness of device benefits and indications
      among physicians responsible for HF care and referral. We aimed to describe the
      awareness of indications for device therapy in a generalized sample of Swedish
      physicians. METHODS AND RESULTS: A randomly selected sample of Swedish physicians
      specializing in cardiology, internal medicine, and family medicine and interns
      (5% of eligible physicians, n = 519) was invited to fill in a 23-item survey,
      testing their awareness of indications for device therapy and, as comparison,
      pharmacological therapy. Acceptable awareness (AA) of CRT indication was
      predefined as recognizing that a left bundle branch block on ECG warrants further
      evaluation for CRT. Acceptable awareness of ICD indication was predefined as
      recognizing that ejection fraction <=35% alone, without a history of ventricular
      tachycardia, is sufficient to warrant a primary prophylactic ICD. The response
      rate was 37% (n = 168). Overall, 32% met AA of CRT indication, and significantly
      less (15%) met AA of ICD indication. Specialist certification in cardiology was
      the only significant predictor for AA [odds ratio (95% confidence interval): 37
      (10-138)]. However, even among cardiologists, awareness of ICD indications was
      low (61% with AA). Guideline-recommended indications for pharmacological therapy
      were conceived significantly better (P = 0.02) than device therapy [median
      (interquartile range) of correct answers: 50% (33-50) compared with 36% (14-57)].
      CONCLUSIONS: The study identified an important and substantial awareness gap in
      the medical community that may explain some of the previously reported low
      referral rates and utilization of device therapy in HF.

PMID- 24451292
TI  - Reduction in STEMI transfer times utilizing a municipal "911" ambulance service.
AB  - INTRODUCTION: The time interval from diagnosis to reperfusion therapy for
      patients experiencing ST-segment elevation myocardial infarction (STEMI) has a
      significant impact on morbidity and mortality. HYPOTHESIS: It is hypothesized
      that the time required for interfacility patient transfers from a community
      hospital to a regional percutaneous coronary intervention (PCI) center using an
      Advanced Life Support (ALS) transfer ambulance service is no different than
      utilizing the "911" ALS ambulance. METHODS: Quality assurance data collected by a
      tertiary care center cardiac catheterization program were reviewed
      retrospectively. Data were collected on all patients with STEMI requiring
      interfacility transfer from a local community hospital to the tertiary care
      center's PCI suite, approximately 16 miles away by ground, 12 miles by air. In
      2009, transfers of patients with STEMI were redirected to the municipal ALS
      ambulance service, instead of the hospital's contracted ALS transfer service.
      Data were collected from January 2007 through May 2013. Temporal data were
      compared between transports initiated through the contracted ALS ambulance
      service and the municipal ALS service. Data points included time of initial
      transport request and time of ambulance arrival to the sending facility and the
      receiving PCI suite. RESULTS: During the 4-year study period, 63 patients
      diagnosed with STEMI and transferred to the receiving hospital's PCI suite were
      included in this study. Mean times from the transport request to arrival of the
      ambulance at the sending hospital's emergency department were six minutes (95%
      CI, 4-7 minutes) via municipal ALS and 13 minutes (95% CI, 9-16 minutes) for the
      ALS transfer service. The mean times from the ground transport request to arrival
      at the receiving hospital's PCI suite when utilizing the municipal ALS ambulance
      and hospital contracted ALS ambulance services were 48 minutes (95% CI, 33-64
      minutes) and 56 minutes (95% CI 52-59 minutes), respectively. This eight-minute
      period represented a 14% (P = .001) reduction in the mean transfer time to the
      PCI suite for patients transported via the municipal ALS ambulance. CONCLUSION:
      In the appropriate setting, the use of the municipal "911" ALS ambulance service
      for the interfacility transport of patients with STEMI appears advantageous in
      reducing door-to-catheterization times.

PMID- 24451293
TI  - Finding the rules for successful drug optimisation.
AB  - Drug discovery is a process of multiparameter optimisation, with the objective of
      finding compounds that achieve multiple, project-specific property criteria.
      These criteria are often based on the subjective opinion of the project team, but
      analysis of historical data can help to find the most appropriate profile.
      Computational 'rule induction' approaches enable an objective analysis of complex
      data to identify interpretable, multiparameter rules that distinguish compounds
      with the greatest likelihood of success for a project. Each property criterion
      highlights the most critical data that enable effective compound prioritisation
      decisions. We illustrate this with two applications: determining rules for
      simple, drug-like properties; and exploring experimental target inhibition data
      to find rules to reduce the risk of toxicity. 

PMID- 24451294
TI  - Addressing toxicity risk when designing and selecting compounds in early drug
      discovery.
AB  - Prioritising compounds with a lower chance of causing toxicity, early in the drug
      discovery process, would help to address the high attrition rate in
      pharmaceutical R&D. Expert knowledge-based prediction of toxicity can alert
      chemists if their proposed compounds are likely to have an increased likelihood
      of causing toxicity. We will discuss how multiparameter optimisation approaches
      can be used to balance the potential for toxicity with other properties required
      in a high-quality candidate drug, giving appropriate weight to the alert in the
      selection of compounds. Furthermore, we will describe how information about the
      region of a compound that triggers a toxicity alert can be interactively
      visualised to guide the modification of a compound to reduce the likelihood of
      toxicity. 

PMID- 24451295
TI  - Isoniazid Pharmacokinetics in the Presence of Ofloxacin and Norfloxacin
      Antibiotics.
AB  - The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on isoniazid (INH)
      pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39
      years after an informed consent. The study was carried out in 3 phases with an
      interval drug wash out period of at least 1 week in between the phases. In phase
      1 (INH alone), subject received 300 mg (usual adult dose) of INH. In phase 2 (INH
      + OXC), 300 mg of INH was coadministered with 200 mg of OXC, and in phase 3 (INH
      + NXC) each received 300 mg of INH together with 400 mg of NXC after 1-week drug
      wash period. Drugs were taken orally with 350 mL of water after an overnight
      fast, and the subject fasted 3 hours after drug. Plasma, saliva, and urine
      concentration of INH were predetermined at zero hour, then hourly until the
      eighth hour, 12 hours, 24 hours, and finally at 48 hours. The urine samples were
      further collected at 72 hours after drug(s) administration using validated
      methods. Various pharmacokinetics parameters were calculated. Various
      pharmacokinetic parameters of INH significantly differed when administered alone
      or in combination with OXC or with NXC. The mean saliva to plasma ratio of INH
      concentration was 0.14. The bioavailability indices of INH in the saliva and
      plasma were similar in all the groups. NXC and OXC reduced the extent and rate of
      absorption of INH. The determination of INH levels in saliva may be useful in
      therapeutic drug monitoring and pharmacokinetic studies.

PMID- 24451296
TI  - Cardiovascular safety monitoring during oncology drug development and therapy.
AB  - Assessments of cardiac and cardiovascular toxicity are prominent components of
      drug safety endeavors during drug development and clinical practice. Oncologic
      drugs bring several challenges to both domains. First, during drug development,
      it is necessary to adapt the ICH E14 "Thorough QT/QTc Study" because the
      cytotoxic nature of many oncologics precludes their being administered to healthy
      individuals. Second, appropriate benefit-risk assessments must be made by
      regulators: given the benefit these drugs provide in life-threatening illnesses,
      a greater degree of risk may be acceptable when granting marketing authorization
      than for drugs for less severe indications. Third, considerable clinical
      consideration is needed for patients who are receiving and have finished
      receiving pharmacotherapy. Paradoxically, although such therapy has proved very
      successful in many cases, with disease states going into remission and patients
      living for many years after cessation of treatment, cardiotoxicities can manifest
      themselves relatively soon or up to a decade later. Oncologic drugs have been
      associated with various off-target cardiovascular responses, including
      cardiomyopathy leading to heart failure, cardiac dysrhythmias, thromboembolic
      events, and hypertension. Follow-up attention and care are, therefore, critical.
      This article reviews the process of benefit-risk estimation, provides an overview
      of nonclinical and preapproval clinical assessment of cardiovascular safety of
      oncology drugs, and discusses strategies for monitoring and management of
      patients receiving drugs with known cardiotoxicity risk. These measures include
      cardiac function monitoring, limitation of chemotherapy dose, use of
      anthracycline analogs and cardioprotectants, and early detection of myocardial
      cell injury using biomarkers. 

PMID- 24451297
TI  - Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.
AB  - Although statins are generally well-tolerated drugs, recent cases of drug-induced
      liver injury associated with their use have been reported. A 52-year-old Chinese
      man reported with liver damage, which appeared 12 hours after beginning treatment
      with fluvastatin. Patient presented with complaints of increasing nausea,
      anorexia, and upper abdominal pain. His laboratory values showed elevated
      creatine kinase and transaminases. Testing for autoantibodies was also negative.
      The liver biochemistries eventually normalized within 3 weeks of stopping the
      fluvastatin. Therefore, when prescribing statins, the possibility of hepatic
      damage should be taken into account. 

PMID- 24451298
TI  - Gemcitabine-Induced Pseudocellulitis in a Patient With Recurrent Lymphedema: A
      Case Report and Review of the Current Literature.
AB  - Gemcitabine is a chemotherapeutic agent used for treatment of a variety of
      malignancies. It has been associated with multiple cutaneous reactions including
      rash, alopecia, and pruritus. Less commonly, gemcitabine has been associated with
      "pseudocellulitis," a noninfectious skin inflammatory reaction, which resembles
      cellulitis. The majority of cases reported in the literature are radiation recall
      reactions in which inflammation occurs in areas of previous radiation post drug
      treatment; however, there are also reports of pseudocellulitis occurring in areas
      of preexisting lymphedema. The pathophysiology of both of these reactions are
      still unknown, though it is theorized that areas of lymphedema may both increase
      concentration of gemcitabine and reduce its rate of metabolism leading to
      increased drug exposure time. In this study, we report a case of pseudocellulitis
      in a patient with chronic lower extremity lymphedema and a review of the current
      literature. By recognizing this side effect of gemcitabine, one can avoid
      unnecessary hospitalization and exposure to antibiotics. 

PMID- 24451299
TI  - Angiotensin-Converting Enzyme Inhibitors--Are They Worth Their Salt?

PMID- 24451300
TI  - Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective
      Cohort Analysis.
AB  - Previous case reports and small studies have suggested that 3-hydroxy-3
      methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of
      tendon rupture. We conducted a population-based retrospective cohort evaluation
      to better assess this relationship. From approximately 800,000 enrollees of a
      private insurance database, those who were aged <=64 years with at least 1 year
      of continuous enrollment were selected. Exposure was defined as initiation of HMG
      CoA-I after the beginning of the study period. Each exposed person was matched
      with 2 controls of similar age and gender. Baseline characteristics, including
      known risk factors for tendon rupture, were compared between exposed and control
      cohorts with fidelity to the study's matched design. After adjusting for
      differences in follow-up and baseline characteristics, incidence rate ratios for
      tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749
      exposed patients were matched with 69,498 controls. There was no difference in
      the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results
      remained unchanged after adjustment for age and gender. In conclusion, this
      population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is
      as a group are not associated with tendon rupture. 

PMID- 24451301
TI  - Challenges in Diagnosis, Management, and Treatment of Allopurinol-Induced DRESS
      Syndrome: Case Report and Literature Review.
AB  - We describe the presentation, diagnosis, management, and treatment of a 62-year
      old woman with a medical history of gout who presented with a maculopapular rash,
      facial and tongue edema. Her initial presentation, coupled with a history of
      recent allopurinol use for systematic relief, led to the diagnosis of allopurinol
      induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome,
      further confirmed by the RegiSCAR scoring criteria including a skin biopsy. The
      patient was initially treated conservatively but required systemic corticosteroid
      therapy as she developed severe multi-organ dysfunction. This article will
      highlight the challenges involved in diagnosing DRESS syndrome from other adverse
      cutaneous drug reactions, delayed systemic complications, and the need for
      evidence-based treatment modalities and regimens using the most recent published
      literature and analysis of case reports. Among treatment modalities, pulsed
      parenteral steroids show promise in a few case reports. We also discuss the newer
      alternative gout therapies since the mainstay of gout treatment, allopurinol, is
      potentially associated with morbidity and mortality risks as manifested in our
      patient with DRESS.

PMID- 24451302
TI  - Murine norovirus infection does not cause major disruptions in the murine
      intestinal microbiota.
AB  - BACKGROUND: Murine norovirus (MNV) is the most common gastrointestinal pathogen
      of research mice and can alter research outcomes in biomedical mouse models of
      inflammatory bowel disease (IBD). Despite indications that an altered microbiota
      is a risk factor for IBD, the response of the murine intestinal microbiota to MNV
      infection has not been examined. Microbiota disruption caused by MNV infection
      could introduce the confounding effects observed in research experiments.
      Therefore, this study investigated the effects of MNV infection on the intestinal
      microbiota of wild-type mice. RESULTS: The composition of the intestinal
      microbiota was assessed over time in both outbred Swiss Webster and inbred
      C57BL/6 mice following MNV infection. Mice were infected with both persistent and
      non-persistent MNV strains and tissue-associated or fecal-associated microbiota
      was analyzed by 16S rRNA-encoding gene pyrosequencing. Analysis of intestinal
      bacterial communities in infected mice at the phylum and family level showed no
      major differences to uninfected controls, both in tissue-associated samples and
      feces, and also over time following infection, demonstrating that the intestinal
      microbiota of wild-type mice is highly resistant to disruption following MNV
      infection. CONCLUSIONS: This is the first study to describe the intestinal
      microbiota following MNV infection and demonstrates that acute or persistent MNV
      infection is not associated with major disruptions of microbial communities in
      Swiss Webster and C57BL/6 mice.

PMID- 24451303
TI  - Locally mediated analgesic effect of bradykinin type 2 receptor antagonist HOE
      140 during acute inflammatory pain in rats.
AB  - Opioids like morphine form the mainstay of treatment for moderate to severe burn
      pain. However, lack of dedicated burn care service and potentially serious side
      effects of opioids often compromise effective treatment. Newer drugs as well as
      newer routes of administration of analgesic drugs are long-felt needs in the
      management of burn pain. Bradykinin is a potent inflammatory mediator present at
      sites of tissue damage. The present study investigated the analgesic effect of
      bradykinin type 2 receptor antagonist HOE 140 after direct intrawound
      administration in rats. Also, whether the analgesic effect was locally mediated
      was further evaluated. Tissue damage was produced by a surgical incision
      involving skin, fascia, and muscle. It has been reported that there are minor
      differences in inflammatory mediators underlying incision-related and burn injury
      related pain. HOE 140 (1, 3, or 10 MUg/10 MUl physiological saline) was
      administered into the wound by a sterile micropipette. After an interval of 30
      seconds, the wound was closed. HOE 140-induced analgesic effect was compared to
      other experimental groups of rats which did not receive any drug or those which
      were treated with either saline (vehicle) or water. Postincisional pain was
      determined by monitoring behavior, allodynia, and thermal hyperalgesia. Analgesic
      effect was also determined after drug administration in contralateral paw. HOE
      140 (1, 3, 10 MUg) significantly relieved mechanical allodynia and guarding in
      comparison with vehicle-treated group. The analgesic effect of HOE 140 was
      locally mediated. Healing of the wound was normal. In conclusion, the results
      suggest that bradykinin type 2 receptor antagonists such as HOE 140 could be
      useful in the treatment of acute inflammatory pain. 

PMID- 24451304
TI  - Can carbohydrate mouth rinse improve performance during exercise? A systematic
      review.
AB  - The purpose of this review was to identify studies that have investigated the
      effect of carbohydrate (CHO) mouth rinse on exercise performance, and to quantify
      the overall mean difference of this type of manipulation across the studies. The
      main mechanisms involving the potential benefit of CHO mouth rinse on performance
      was also explored. A systematic review was conducted in the following electronic
      databases: PubMed, SciELO, Science Direct, MEDLINE, and the Cochrane Library
      (Cochrane Central Register of Controlled Trials), without limit of searches.
      Eleven studies were classified as appropriate and their results were summarized
      and compared. In nine of them, CHO mouth rinse increased the performance (range
      from 1.50% to 11.59%) during moderate- to high-intensity exercise (~75% Wmax or
      65% VO2max, ~1 h duration). A statistical analysis to quantify the individual and
      overall mean differences was performed in seven of the 11 eligible studies that
      reported power output (watts, W) as the main performance outcome. The overall
      mean difference was calculated using a random-effect model that accounts for true
      variation in effects occurring in each study, as well as random error within a
      single study. The overall effect of CHO mouth rinse on performance was
      significant (mean difference=5.05 W, 95% CI 0.90 to 9.2 W, z=2.39, p=0.02) but
      there was a large heterogeneity between the studies (I2=52%). An activation of
      the oral receptors and consequently brain areas involved with reward
      (insula/operculum frontal, orbitofrontal cortex, and striatum) is suggested as a
      possible physiological mechanism responsible for the improved performance with
      CHO mouth rinse. However, this positive effect seems to be accentuated when
      muscle and liver glycogen stores are reduced, possibly due to a greater
      sensitivity of the oral receptors, and require further investigation. Differences
      in duration of fasting before the trial, duration of mouth rinse, type of
      activity, exercise protocols, and sample size may account for the large
      variability between the studies.

PMID- 24451305
TI  - Vitamin D and human health: celebrating diversity.

PMID- 24451306
TI  - The prevalence of antibodies against wheat and milk proteins in blood donors and
      their contribution to neuroimmune reactivities.
AB  - The aim of this study was to look for the presence of IgG, IgM, and IgA
      antibodies against two widely consumed foods, wheat and milk, in a relatively
      large number of specimens. As wheat, milk, and their antigens have been found to
      be involved in neuroimmune disorders, we measured the co-occurrence of their
      antibodies against various neural antigens. We assessed the reactivity of sera
      from 400 donors to wheat and milk proteins, GAD-65, cerebellar, MBP, and MOG.
      Statistical analysis showed significant clustering when certain wheat and milk
      protein antibodies were cross-referenced with neural antibodies. Approximately
      half of the sera with antibody elevation against gliadin reacted significantly
      with GAD-65 and cerebellar peptides; about half of the sera with elevated
      antibodies against alpha + beta-casein and milk butyrophilin also showed antibody
      elevation against MBP and MOG. Inhibition studies showed that only two out of
      four of the samples with elevated cerebellar or MOG antibodies could be inhibited
      by gliadin or alpha + beta-casein, confirming individual variation in epitope
      recognition. We conclude that a subgroup of blood donors, due to a breakdown in
      immunological tolerance, may react and produce significant levels of antibodies
      (p-values less than 0.05) against wheat and milk antigens that cross-react with
      different neural antigens, which may have broader implications in the induction
      of neuroimmune reactivities. 

PMID- 24451307
TI  - 24-h fluid kinetics and perception of sweat losses following a 1-h run in a
      temperate environment.
AB  - This study examined 24-h post-run hydration status and sweat loss estimation
      accuracy in college age runners (men=12, women=8) after completing a 1-h self
      paced outdoor run (wet bulb globe temperature=19.9+/-3.0  degrees C). Sweat
      losses (1353+/-422 mL; 1.9%+/-0.5% of body mass) were significantly greater
      (p<0.001) than perceived losses (686+/-586 mL). Cumulative fluid consumption
      equaled 3876+/-1133 mL (218+/-178 mL during) with 37% of fluid ingested lost
      through urine voids (1450+/-678 mL). Fluid balance based on intake and urine
      production equaled +554+/-669 mL at 12 h and +1186+/-735 mL at 24 h. Most runners
      reported euhydrated (pre-run urine specific gravity (USG)=1.018+/-0.008) with no
      changes (p=0.33) at hours 12 or 24 when both genders were included. However, USG
      was higher (p=0.004) at 12 h post-run for men (1.025+/-0.0070 vs. 1.014+/-0.007),
      who consumed 171%+/-40% of sweat losses at 12 h vs. 268%+/-88% for women. Most
      runners do not need intervention concerning between bout hydration needs in
      temperate environments. However, repeated USG measurements were able to identify
      runners who greatly under or over consumed fluid during recovery. Practitioners
      can use multiple USG assessments as cheap method to detect runners who need to
      modify their hydration strategies and should promote assessment of sweat losses
      by change in body mass, as runners had poor perception of sweat losses.

PMID- 24451308
TI  - Celiac disease and overweight in children: an update.
AB  - The clinical presentation of celiac disease in children is very variable and
      differs with age. The prevalence of atypical presentations of celiac disease has
      increased over the past 2 decades. Several studies in adults and children with
      celiac disease indicate that obesity/overweight at disease onset is not unusual.
      In addition, there is a trend towards the development of overweight/obesity in
      celiac patients who strictly comply with a gluten-free diet. However, the
      pathogenesis and clinical implications of the coexistence of classic
      malabsorption (e.g., celiac disease) and overweight/obesity remain unclear. This
      review investigated the causes and main clinical factors associated with
      overweight/obesity at the diagnosis of celiac disease and clarified whether
      gluten withdrawal affects the current trends of the nutritional status of celiac
      disease patients. 

PMID- 24451309
TI  - Association between serum 25-hydroxyvitamin D and inflammatory cytokines in
      healthy adults.
AB  - Here, we aimed to examine the associations between levels of serum 25
      hydroxyvitamin D [25(OH)D] and inflammatory cytokines in healthy Japanese adults.
      A total of 95 healthy adults (61 women; age range 21-69 years) participated in
      our study. Fasting blood samples were analyzed for 25(OH)D, 1,25-dihydroxyvitamin
      D [1,25(OH)2D], interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and
      interleukin-17 (IL-17) levels using enzyme-linked immunosorbent assays kits.
      Total percent body fat was determined by dual energy X-ray absorptiometry (DXA).
      Moderate to vigorous physical activity (MVPA) was assessed objectively using an
      activity monitor for 7 days. The mean 25(OH)D concentration was 34.7 nmol/L, and
      83 subjects had 25(OH)D concentrations less than 50 nmol/L. Multiple linear
      regression analysis revealed that serum 25(OH)D level was positively related to
      plasma IL-17 level (beta=0.26, p=0.025), after adjustment for gender, age,
      vitamin D intake, alcohol consumption, smoking status, and percent body fat. This
      relationship remained statistically significant (beta=0.28, p=0.019) even after
      additional adjustment for MVPA. However, no significant association was found
      between serum 25(OH)D level and plasma IFN-gamma or IL-6 levels. In conclusion,
      this study identified a high prevalence of vitamin D deficiency in healthy
      Japanese adults. Serum 25(OH)D level was positively related to IL-17 level,
      independent of physical activity.

PMID- 24451310
TI  - Recent advances and uses of grape flavonoids as nutraceuticals.
AB  - Grape is one of the oldest fruit crops domesticated by humans. The numerous uses
      of grape in making wine, beverages, jelly, and other products, has made it one of
      the most economically important plants worldwide. The complex phytochemistry of
      the berry is characterized by a wide variety of compounds, most of which have
      been demonstrated to have therapeutic or health promoting properties. Among them,
      flavonoids are the most abundant and widely studied, and have enjoyed greater
      attention among grape researchers in the last century. Recent studies have shown
      that the beneficial health effects promoted by consumption of grape and grape
      products are attributed to the unique mix of polyphenolic compounds. As the
      largest group of grape polyphenols, flavonoids are the main candidates considered
      to have biological properties, including but not limited to antioxidant, anti
      inflammatory, anti-cancer, antimicrobial, antiviral, cardioprotective,
      neuroprotective, and hepatoprotective activities. Here, we discuss the recent
      scientific advances supporting the beneficial health qualities of grape and grape
      derived products, mechanisms of their biological activity, bioavailability, and
      their uses as nutraceuticals. The advantages of modern plant cell based
      biotechnology as an alternative method for production of grape nutraceuticals and
      improvement of their health qualities are also discussed. 

PMID- 24451311
TI  - Nutrition prescription to achieve positive outcomes in chronic kidney disease: a
      systematic review.
AB  - In Chronic Kidney Disease (CKD), management of diet is important in prevention of
      disease progression and symptom management, however evidence on nutrition
      prescription is limited. Recent international CKD guidelines and literature was
      reviewed to address the following question "What is the appropriate nutrition
      prescription to achieve positive outcomes in adult patients with chronic kidney
      disease?" Databases included in the search were Medline and CINAHL using
      EBSCOhost search engine, Embase and the Cochrane Database of Systematic Reviews
      published from 2000 to 2009. International guidelines pertaining to nutrition
      prescription in CKD were also reviewed from 2000 to 2013. Three hundred and
      eleven papers and eight guidelines were reviewed by three reviewers. Evidence was
      graded as per the National Health and Medical Research Council of Australia
      criteria. The evidence from thirty six papers was tabulated under the following
      headings: protein, weight loss, enteral support, vitamin D, sodium, fat, fibre,
      oral nutrition supplements, nutrition counselling, including protein and
      phosphate, nutrients in peritoneal dialysis solution and intradialytic parenteral
      nutrition, and was compared to international guidelines. While more evidence
      based studies are warranted, the customary nutrition prescription remains
      satisfactory with the exception of Vitamin D and phosphate. In these two areas,
      additional research is urgently needed given the potential of adverse outcomes
      for the CKD patient. 

PMID- 24451318
TI  - Technological assessment of the biogalvanic method for tissue characterization.
AB  - Biogalvanic cells have the potential to be used in characterizing biological
      tissue properties and ultimately tissue health. A biogalvanic cell is established
      by placing two differing metal electrodes across a target tissue allowing an
      electrical tissue-specific internal resistance to be determined. A novel data
      analysis method using least-squares fitting has been developed to more
      effectively determine the parameters of the biogalvanic system model proposed in
      the literature. The validity of the method has been examined through
      characterization of electrical models, ex vivo porcine tissue, and in vivo
      porcine tissue. Strong agreement between test results and the proposed
      characterization model has been shown. However, determined internal resistances
      are influenced by mechanical strain, current modulation direction and tissue
      thickness, indicating complexities at the electrode-tissue interface. These
      complexities undermine some assumptions upon which the biogalvanic model is
      based. Ultimately this technique could offer potential for use in minimally
      invasive surgery for discriminating tissue health but requires improved
      understanding and control of testing conditions.

PMID- 24451312
TI  - Association between lutein and zeaxanthin status and the risk of cataract: a meta
      analysis.
AB  - The purpose of this meta-analysis was to evaluate the relationship between blood
      lutein and zeaxanthin concentration and the risk of age-related cataract (ARC).
      MEDLINE, EMBASE, ISI and Cochrane Library were searched to identify relevant
      studies up to April 2013. Meta-analysis was conducted to obtain pooled relative
      risks (RRs) for the highest-versus-lowest categories of blood lutein and
      zeaxanthin concentrations. One cohort study and seven cross-sectional studies
      were included in the meta-analysis. There were significant inverse associations
      between nuclear cataract and blood lutein and zeaxanthin concentrations, with the
      pooled RRs ranging from 0.63 (95% confidence interval (CI): 0.49, 0.77) for
      zeaxanthin to 0.73 (95% CI: 0.59, 0.87) for lutein. A stronger association
      between nuclear cataract and blood zeaxanthin might be noted for the studies
      conducted in the European Nations. Blood lutein and zeaxanthin were also noted to
      lead towards a decrease in the risk of cortical cataract and subcapsular
      cataract; however, these pooled RRs were not statistically significant, with the
      exception of a marginal association between lutein and subcapsular cataract. Our
      results suggest that high blood lutein and zeaxanthin are significantly
      associated with a decrease in the risk of nuclear cataract. However, no
      significant associations were found for ARC in other regions of the lens. 

PMID- 24451321
TI  - Magnetic and magnetothermal properties and the magnetic phase diagram of high
      purity single crystalline terbium along the easy magnetization direction.
AB  - The magnetic and magnetothermal properties of a high purity terbium single
      crystal have been re-investigated from 1.5 to 350 K in magnetic fields ranging
      from 0 to 75 kOe using magnetization, ac magnetic susceptibility and heat
      capacity measurements. The magnetic phase diagram has been refined by
      establishing a region of the fan-like phase broader than reported in the past, by
      locating a tricritical point at 226 K, and by a more accurate definition of the
      critical fields and temperatures associated with the magnetic phases observed in
      Tb.

PMID- 24451322
TI  - Rictor/mTORC2 protects against cisplatin-induced tubular cell death and acute
      kidney injury.
AB  - The mammalian target of rapamycin (mTOR) plays a critical role for cell growth
      and survival in many cell types. While substantial progress has been made in
      understanding the abnormal activation of mTORC1 in the pathogenesis of kidney
      disease, little is known about mTORC2 in kidney disease such as acute kidney
      injury (AKI). To study this, we generated a mouse model with tubule-specific
      deletion of Rictor (Tubule-Rictor-/-). The knockouts were born normal and no
      obvious kidney dysfunction or kidney morphologic abnormality was found within 2
      months of birth. However, ablation of Rictor in the tubular cells exacerbated
      cisplatin-induced AKI compared to that in the control littermates. As expected,
      tubular cell apoptosis, Akt phosphorylation (Ser473), and autophagy were induced
      in the kidneys from the control littermates by cisplatin treatment. Less cell
      autophagy or Akt phosphorylation and more cell apoptosis in the kidneys of the
      knockout mice were identified compared with those in the control littermates. In
      NRK-52E cells in vitro, Rictor siRNA transfection sensitized cell apoptosis to
      cisplatin but with reduced cisplatin-induced autophagy. Metformin, an inducer of
      autophagy, abolished cell death induced by Rictor siRNA and cisplatin. Thus,
      endogenous Rictor/mTORC2 protects against cisplatin-induced AKI, probably
      mediated by promoting cell survival through Akt signaling activation and
      induction of autophagy. 

PMID- 24451323
TI  - Increased risk of solid renal tumors in lithium-treated patients.
AB  - Cystic kidney diseases and toxic interstitial nephritis may be complicated by
      renal tumors. Long-term lithium intake is associated with tubulointerstitial
      nephritis and renal cysts but to date such an association with tumors has not
      been determined. We evaluated this in a retrospective study to determine whether
      lithium-treated patients were at higher risk of renal tumors compared with
      lithium-free patients with chronic kidney disease (CKD), and to the general
      population. Over a 16-year period, 14 of 170 lithium-treated patients had renal
      tumors, including seven malignant and seven benign tumors. The mean duration of
      lithium exposure at diagnosis was 21.4 years. The renal cancers included three
      clear-cell and two papillary renal cell carcinomas, one hybrid tumor with
      chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with
      leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed
      epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal
      tumors, particularly cancers and oncocytomas, was significantly higher in lithium
      treated patients compared with 340 gender-, age-, and estimated glomerular
      filtration rate (eGFR)-matched lithium-free patients. Additionally, the
      Standardized Incidence Ratio of renal cancer was significantly higher in lithium
      treated patients compared with the general population: 7.51 (95% confidence
      interval (CI) (1.51-21.95)) and 13.69 (95% CI (3.68-35.06)) in men and women,
      respectively. Thus, there is an increased risk of renal tumors in lithium-treated
      patients. 

PMID- 24451324
TI  - Characterization and outcomes of renal leukocyte chemotactic factor 2-associated
      amyloidosis.
AB  - Amyloidosis derived from leukocyte chemotactic factor 2 (ALECT2) is a recently
      described disease. Here, we report the characteristics and outcome of 72 patients
      with renal ALECT2, which included 19 who had another kidney disease on biopsy.
      Ninety-two percent of patients were Hispanics and over half were elderly. Three
      had other organ, but not cardiac, amyloidosis involvement. All patients without
      concurrent disease, except three, presented with chronic renal insufficiency.
      Proteinuria was variable and absent in a third, whereas nephrotic syndrome and
      hematuria were rare. After a median follow-up of 26 months, one-third developed
      end-stage renal disease (ESRD). The median renal survival was 62 months.
      Independent predictors of renal survival were serum creatinine at diagnosis, with
      a value of 2.0 mg/dl being the best cutoff for predicting ESRD, percentage global
      glomerulosclerosis, and presence of diabetes. Only four patients died and four
      had received chemotherapy for an erroneous diagnosis of immunoglobulin light
      chain-derived amyloidosis. Five patients underwent kidney transplantation; none
      had graft loss but one had disease recurrence. Patient survival is superior to
      renal immunoglobulin light chain-derived amyloidosis and reactive amyloidosis
      largely due to the absence of cardiac involvement. Thus, renal ALECT2 mainly
      affects elderly Hispanics who typically present with chronic renal insufficiency
      and bland urine sediment, with or without proteinuria. 

PMID- 24451325
TI  - Functional divergence for every paralog.
AB  - Because genes can be constrained by selection at more than one phenotypic level,
      the relaxation of constraints following gene duplication allows for functional
      divergence (FD) along multiple phenotypic axes. Many studies have generated
      individual measures of FD, but the profile of FD between paralogs across levels
      of phenotypic space remains largely uncharted. We evaluate paralog pairs that
      originated via the yeast whole-genome duplication (ohnolog pairs) at three
      distinct phenotypic levels (properties of proteins, gene expression, and overall
      organismal growth) using eight complementary measures of FD (protein:
      evolutionary rates, radical amino acid substitutions, and domain architecture;
      gene expression: expression differences in a single species and condition, across
      species in a single condition, and in a single species across conditions; and
      organismal: genetic interaction profiles and growth profiles in multiple
      conditions). We find that the majority of ohnolog pairs show FD by multiple
      phenotypic measures. Within each phenotypic level, measures of FD are strongly
      correlated but are generally weakly correlated between levels, suggesting that
      functional constraints exerted on genes from distinct phenotypic levels are
      largely decoupled. Our results suggest that redundancy is a rare functional fate
      for retained paralogs and that FD cannot be fully captured by measures at any
      single phenotypic level. 

PMID- 24451326
TI  - The contribution of SERF1 to root-to-shoot signaling during salinity stress in
      rice.
AB  - Stress perception and communication play important roles in the adaptation of
      plants to changing environmental conditions. Plant roots are the first organs to
      detect changes in the soil water potential induced by salt stress. In the
      presence of salinity stress, root-to-shoot communication occurs to adjust the
      growth of the whole plant. So far, the phytohormone abscisic acid (ABA),
      hydraulic signals and reactive oxygen species (ROS) have been proposed to mediate
      this communication under salt stress. Recently, we identified the rice
      transcription factor SALT-RESPONSIVE ERF1 (SERF1), which regulates a ROS
      dependent transcriptional cascade in roots required for salinity tolerance. Upon
      salt stress, SERF1 knockout mutant plants show an increased leaf temperature as
      compared with wild type. As this occurs within the first 20 min of salt stress,
      we here evaluated the involvement of SERF1 in the perception of salt stress in
      the shoot. By metabolic profiling and expression analysis we show that the action
      of SERF1 in signal communication to the shoot is independent from ABA, but does
      affect the accumulation of ROS-related metabolites and transcripts under short
      term salt stress. 

PMID- 24451327
TI  - Purification, stability, and immunogenicity analyses of five bluetongue virus
      proteins for use in development of a subunit vaccine that allows differentiation
      of infected from vaccinated animals.
AB  - Bluetongue virus (BTV) causes bluetongue disease, a vector-borne disease of
      ruminants. The recent northerly spread of BTV serotype 8 in Europe resulted in
      outbreaks characterized by clinical signs in cattle, including unusual
      teratogenic effects. Vaccination has been shown to be crucial for controlling the
      spread of vector-borne diseases such as BTV. With the aim of developing a novel
      subunit vaccine targeting BTV-8 that allows differentiation of infected from
      vaccinated animals, five His-tagged recombinant proteins, VP2 and VP5 of BTV-8
      and NS1, NS2, and NS3 of BTV-2, were expressed in baculovirus or Escherichia coli
      expression systems for further study. Optimized purification protocols were
      determined for VP2, NS1, NS2, and NS3, which remained stable for detection for at
      least 560 to 610 days of storage at +4 degrees C or -80 degrees C, and Western
      blotting using sera from vaccinated or experimentally infected cattle indicated
      that VP2 and NS2 were recognized by BTV-specific antibodies. To characterize
      murine immune responses to the four proteins, mice were subcutaneously immunized
      twice at a 4-week interval with one of three protein combinations plus
      immunostimulating complex ISCOM-Matrix adjuvant or with ISCOM-Matrix alone (n = 6
      per group). Significantly higher serum IgG antibody titers specific for VP2 and
      NS2 were detected in immunized mice than were detected in controls. VP2, NS1, and
      NS2 but not NS3 induced specific lymphocyte proliferative responses upon
      restimulation of spleen cells from immunized mice. The data suggest that these
      recombinant purified proteins, VP2, NS1, and NS2, could be an important part of a
      novel vaccine design against BTV-8. 

PMID- 24451328
TI  - Flagellin a toll-like receptor 5 agonist as an adjuvant in chicken vaccines.
AB  - Chicken raised under commercial conditions are vulnerable to environmental
      exposure to a number of pathogens. Therefore, regular vaccination of the flock is
      an absolute requirement to prevent the occurrence of infectious diseases. To
      combat infectious diseases, vaccines require inclusion of effective adjuvants
      that promote enhanced protection and do not cause any undesired adverse reaction
      when administered to birds along with the vaccine. With this perspective in mind,
      there is an increased need for effective better vaccine adjuvants. Efforts are
      being made to enhance vaccine efficacy by the use of suitable adjuvants,
      particularly Toll-like receptor (TLR)-based adjuvants. TLRs are among the types
      of pattern recognition receptors (PRRs) that recognize conserved pathogen
      molecules. A number of studies have documented the effectiveness of flagellin as
      an adjuvant as well as its ability to promote cytokine production by a range of
      innate immune cells. This minireview summarizes our current understanding of
      flagellin action, its role in inducing cytokine response in chicken cells, and
      the potential use of flagellin as well as its combination with other TLR ligands
      as an adjuvant in chicken vaccines. 

PMID- 24451329
TI  - An attenuated duck plague virus (DPV) vaccine induces both systemic and mucosal
      immune responses to protect ducks against virulent DPV infection.
AB  - Duck plague (DP) is a severe disease caused by DP virus (DPV). Control of the
      disease is recognized as one of the biggest challenges in avian medicine.
      Vaccination is an efficient way to control DPV, and an attenuated vaccine is the
      main routine vaccine. The attenuated DPV vaccine strain CHa is a modified live
      vaccine, but the systemic and mucosal immune responses induced by this vaccine
      have been poorly understood. In this study, the immunogenicity and efficacy of
      the vaccine were evaluated after subcutaneous immunization of ducks. CD4(+) and
      CD8(+) T cells were counted by flow cytometry, and humoral and mucosal Ig
      antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA). The
      results showed that high levels of T cells and Ig antibodies were present
      postimmunization and that there were more CD4(+) T cells than CD8(+) T cells.
      Titers of humoral IgG were higher than those of humoral IgA. Local IgA was found
      in each sample, whereas local IgG was found only in the spleen, thymus, bursa of
      Fabricius, harderian gland, liver, bile, and lung. In a protection assay, the
      attenuated DPV vaccine completely protected ducks against 1,000 50% lethal doses
      (LD50) of the lethal DPV strain CHv via oral infection. These data suggest that
      this subcutaneous vaccine elicits sufficient systemic and mucosal immune
      responses against lethal DPV challenge to be protective in ducks. This study
      provides broad insights into understanding the immune responses to the attenuated
      DPV vaccine strain CHa through subcutaneous immunization in ducks. 

PMID- 24451330
TI  - Serodiagnosis of equine leptospirosis by enzyme-linked immunosorbent assay using
      four recombinant protein markers.
AB  - Leptospirosis, caused by Leptospira spp., is one of the most common zoonotic
      diseases in the world. We tested four recombinant proteins of Leptospira
      interrogans, namely, rLipL21, rLoa22, rLipL32, and rLigACon4-8, to evaluate their
      potential for use as antigens for the diagnosis of equine leptospirosis. We
      employed equine sera (n = 130) that were microscopic agglutination test (MAT)
      negative and sera (n = 176) that were MAT positive for the 5 serovars that most
      commonly cause equine leptospirosis. The sensitivity and specificity of ELISA
      compared to MAT were 82.39% and 86.15%, respectively, for LigACon4-8, 77.84% and
      92.31%, respectively, for Loa22, 77.84% and 86.15%, respectively, for LipL32, and
      84.66% and 83.85%, respectively, for LipL21. When one of the two antigens was
      test positive, the sensitivity and specificity of ELISA were 93.75% and 78.46%,
      respectively, for rLigACon4-8 and LipL32, 93.18% and 76.15%, respectively, for
      rLigACon4-8 and LipL21, 89.77% and 80.77%, respectively, for rLigACon4-8 and
      Loa22, 91.48% and 78.46%, respectively, for LipL21 and Loa22, 93.75% and 76.92%,
      respectively, for LipL21 and LipL32, and 90.34% and 80.77%, respectively, for
      Loa22 and LipL32. In conclusion, we have developed an indirect ELISA utilizing
      rLigACon4-8, rLoa22, rLipL32, and rLipL21 as diagnostic antigens for equine
      leptospirosis. The use of four antigens in the ELISA was found to be sensitive
      and specific, the assay was easy to perform, and the results concurred with the
      results of the standard Leptospira MAT. 

PMID- 24451332
TI  - Disaster health after the 2011 great East Japan earthquake.
AB  - INTRODUCTION: The March 11, 2011 disaster was unparalleled in the disaster
      history of Japan. There is still enormous effort required in order for Japan to
      recover from the damage, not only financially, but psychosocially. This paper is
      a review of the studies that have been undertaken since this disaster, from after
      the March 11th disaster in 2011 to the end of 2012, and will provide an overview
      of the disaster-health research literature published during this period. METHODS:
      The Japanese database Ichushi Ver. 5 was used to review the literature. This
      database is the most frequently used database in Japanese health-sciences
      research. The keywords used in the search were "Higashi Nihon Dai-shinsai" (The
      Great East Japan Earthquake). RESULTS: A total of 5,889 articles were found.
      Within this selection, 163 articles were categorized as original research (gencho
      ronbun). The articles were then sorted and the top four key categories were as
      follows: medicine (n = 98), mental health (n = 18), nursing (n = 13), and
      disaster management (n = 10). Additional categories were: nutrition (n = 4),
      public health (n = 3), radiology, preparedness, and pharmacology (n = 2 for each
      category). Nine articles appeared with only one category label and were grouped
      as "others." CONCLUSION: This review provides the current status of disaster
      health research following the Great East Japan Earthquake. The research focus
      over the selected period was greatly directed towards medical considerations,
      especially vascular conditions and renal dialysis. Considering the compounding
      factors of the cold temperatures at the time of the disaster, the geography, the
      extensive dislocation of the population, and the demographics of an aging
      community, it is noteworthy that the immediate and acute impact of the March 11th
      disaster was substantial compared with other events and their studies on the
      impact of disaster on chronic and long-term illness. The complexity of damage
      caused by the earthquake event and the associated nuclear power plant event,
      which possibly affected people more psychologically than physically, might also
      need to be investigated with respect to long term objectives for improving
      disaster preparedness and management.

PMID- 24451333
TI  - Are there specific indications for the different alveolar bone augmentation
      procedures for implant placement? A systematic review.
AB  - Bone resorption following tooth loss often interferes with dental implant
      placement in a desired position, and requires additional bone augmentation
      procedures. Many techniques have been described to augment and reconstruct
      alveolar ridge width and height. The aim of this study was to systemically review
      whether there is evidence to provide indications for the various bone
      augmentation procedures based on defect dimension and type. An electronic search
      of the Medline database and Cochrane library, complemented by a manual search,
      was performed. Inclusion criteria for partial edentulism were: clinical trials on
      bone augmentation procedures in preparation or at the time of implant placement,
      reporting preoperative and postoperative dimensions of the ridge. For edentulous
      patients, studies were included when providing the data on ridge and defect
      description, or the amount of augmentation achieved. The search yielded 53
      publications for partially edentulous patients and 15 publications for edentulous
      patients. The literature provides evidence that dehiscence and fenestrations can
      be treated successfully with guided bone regeneration (GBR) at the time of
      implant placement (mean implant survival rate (MISR) 92.2%, mean complication
      rate (MCR) 4.99%). In partially edentulous ridges, when a horizontal defect is
      present, procedures such as staged GBR (MISR 100%, MCR 11.9%), bone block grafts
      (MISR 98.4%, MCR 6.3%), and ridge expansion/splitting (MISR 97.4%, MCR 6.8%) have
      proved to be effective. Vertical defects can be treated with simultaneous and
      staged GBR (MISR 98.9%, MCR 13.1% and MISR 100%, MCR 6.95%, respectively), bone
      block grafts (MISR 96.3%, MCR 8.1%), and distraction osteogenesis (MISR 98.2%,
      MCR 22.4%). In edentulous patients, there is evidence that bone block grafts can
      be used (MISR 87.75%), and that Le Fort I osteotomies can be applied (MISR
      87.9%), but associated with a high complication rate. The objective of extracting
      specific indications for each procedure could not be fully achieved due to the
      heterogeneity of the studies available. Further studies on bone augmentation
      procedures should report precise preoperative and postoperative measurements to
      enable a more exact analysis of the augmentation procedure, as well as to provide
      the clinician with the rationale for choosing the most indicated surgical
      approach.

PMID- 24451331
TI  - Inclusion of the bovine neutrophil beta-defensin 3 with glycoprotein D of bovine
      herpesvirus 1 in a DNA vaccine modulates immune responses of mice and cattle.
AB  - Bovine herpesvirus 1 (BoHV-1) causes recurrent respiratory and genital infections
      in cattle and predisposes them to lethal secondary infections. While modified
      live and killed BoHV-1 vaccines exist, these are not without problems.
      Development of an effective DNA vaccine for BoHV-1 has the potential to address
      these issues. As a strategy to enhance DNA vaccine immunity, a plasmid encoding
      the bovine neutrophil beta-defensin 3 (BNBD3) as a fusion with truncated
      glycoprotein D (tgD) and a mix of two plasmids encoding BNBD3 and tgD were tested
      in mice and cattle. In mice, coadministration of BNBD3 on the separate plasmid
      enhanced the tgD-induced gamma interferon (IFN-gamma) response but not the
      antibody response. BNBD3 fused to tgD did not affect the antibody levels or the
      number of IFN-gamma-secreting cells but increased the induction of tgD-specific
      cytotoxic T lymphocytes (CTLs). In cattle, the addition of BNBD3 as a fusion
      construct also modified the immune response. While the IgG and virus-neutralizing
      antibody levels were not affected, the number of IFN-gamma-secreting cells was
      increased after BoHV-1 challenge, specifically the CD8(+) IFN-gamma(+) T cells,
      including CD8(+) IFN-gamma(+) CD25(+) CTLs. While reduced virus shedding, rectal
      temperature, and weight loss were observed, the level of protection was
      comparable to that observed in pMASIA-tgD-vaccinated animals. These data show
      that coadministration of BNBD3 with a protective antigen as a fusion in a DNA
      vaccine strengthened the Th1 bias and increased cell-mediated immune responses
      but did not enhance protection from BoHV-1 infection. 

PMID- 24451334
TI  - A gene-targeted approach to investigate the intestinal butyrate-producing
      bacterial community.
AB  - BACKGROUND: Butyrate, which is produced by the human microbiome, is essential for
      a well-functioning colon. Bacteria that produce butyrate are phylogenetically
      diverse, which hinders their accurate detection based on conventional
      phylogenetic markers. As a result, reliable information on this important
      bacterial group is often lacking in microbiome research. RESULTS: In this study
      we describe a gene-targeted approach for 454 pyrotag sequencing and quantitative
      polymerase chain reaction for the final genes in the two primary bacterial
      butyrate synthesis pathways, butyryl-CoA:acetate CoA-transferase (but) and
      butyrate kinase (buk). We monitored the establishment and early succession of
      butyrate-producing communities in four patients with ulcerative colitis who
      underwent a colectomy with ileal pouch anal anastomosis and compared it with
      three control samples from healthy colons. All patients established an abundant
      butyrate-producing community (approximately 5% to 26% of the total community) in
      the pouch within the 2-month study, but patterns were distinctive among
      individuals. Only one patient harbored a community profile similar to the healthy
      controls, in which there was a predominance of but genes that are similar to
      reference genes from Acidaminococcus sp., Eubacterium sp., Faecalibacterium
      prausnitzii and Roseburia sp., and an almost complete absence of buk genes. Two
      patients were greatly enriched in buk genes similar to those of Clostridium
      butyricum and C. perfringens, whereas a fourth patient displayed abundant
      communities containing both genes. Most butyrate producers identified in previous
      studies were detected and the general patterns of taxa found were supported by
      16S rRNA gene pyrotag analysis, but the gene-targeted approach provided more
      detail about the potential butyrate-producing members of the community.
      CONCLUSIONS: The presented approach provides quantitative and genotypic insights
      into butyrate-producing communities and facilitates a more specific functional
      characterization of the intestinal microbiome. Furthermore, our analysis refines
      but and buk reference annotations found in central databases.

PMID- 24451335
TI  - Gait disturbances in patients with stroke.
AB  - Poststroke hemiplegic gait is a mixture of deviations and compensatory motion
      dictated by residual functions, and thus each patient must be examined and
      his/her unique gait pattern identified and documented. Quantitative 3-dimensional
      gait analysis is the best way to understand the complex multifactorial gait
      dysfunction in hemiparetic patients. The goals of the present work are to (1)
      review the temporospatial, kinematic, kinetic, and electromyographic deviations
      from normal gait that commonly occur after stroke and are of clinical
      significance, along with the most likely causes of these deviations, and (2)
      differentiate the departures from normal gait parameters that arise as a direct
      consequence of poststroke motor problems and those that arise as learned or
      adaptive compensations for poststroke motor problems. 

PMID- 24451343
TI  - Biological materials by design.
AB  - In this topical review we discuss recent advances in the use of physical insight
      into the way biological materials function, to design novel engineered materials
      'from scratch', or from the level of fundamental building blocks upwards and by
      using computational multiscale methods that link chemistry to material function.
      We present studies that connect advances in multiscale hierarchical material
      structuring with material synthesis and testing, review case studies of wood and
      other biological materials, and illustrate how engineered fiber composites and
      bulk materials are designed, modeled, and then synthesized and tested
      experimentally. The integration of experiment and simulation in multiscale design
      opens new avenues to explore the physics of materials from a fundamental
      perspective, and using complementary strengths from models and empirical
      techniques. Recent developments in this field illustrate a new paradigm by which
      complex material functionality is achieved through hierarchical structuring in
      spite of simple material constituents. 

PMID- 24451336
TI  - Life care planning: a natural domain of physiatry.
AB  - This article is an introduction to life care planning and its relevance to
      physiatry and physiatric practice. It includes a discussion of life care
      planning, physiatry's role within its history and evolution, and life care
      planning methodologies. It also discusses life care planning education and
      certification, how the core competencies of the physiatrist are particularly
      relevant and applicable to life care planning, and life care planning's capacity
      to complement and diversify a clinical physiatric practice.

PMID- 24451345
TI  - Drug response depends on mouse substrain.

PMID- 24451346
TI  - Cell communication feeds the fountain of youth.

PMID- 24451348
TI  - A wake-up call for injured neurons.

PMID- 24451349
TI  - Excess fat reprograms circadian rhythms.

PMID- 24451351
TI  - Neuroscience 2013.

PMID- 24451352
TI  - The Arabian horse SCIDs to a halt.

PMID- 24451353
TI  - The regulatory process.

PMID- 24451354
TI  - Response to protocol review scenario: Chair should be a voting member.

PMID- 24451355
TI  - An IACUC Chair who isn't a member.

PMID- 24451356
TI  - Response to protocol review scenario: Legal, but is it effective?

PMID- 24451357
TI  - Response to protocol review scenario: Conflict of interest.

PMID- 24451358
TI  - Response to protocol review scenario: A word from OLAW and USDA.

PMID- 24451360
TI  - Effects of short-term niacin treatment on plasma lipoprotein concentrations in
      African green monkeys (Chlorocebus aethiops).
AB  - Niacin is the most effective drug available for raising levels of high-density
      lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid
      concentrations, the authors administered a low dose of niacin to healthy, adult,
      female African green monkeys for 3 months. In the treated monkeys, low-density
      lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas
      concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and
      34%, respectively. The results suggest that in this primate model, a low dose of
      niacin can effectively increase concentrations of HDL cholesterol. 

PMID- 24451361
TI  - Safety and blood sample volume and quality of a refined retro-orbital bleeding
      technique in rats using a lateral approach.
AB  - The collection of blood samples from laboratory rats requires the use of bleeding
      techniques that provide quality samples of sufficient volume for analysis without
      injury to the animal. Retro-orbital bleeding (ROB) is a phlebotomy technique that
      can yield high-quality samples of adequate volume, but it has been criticized for
      its potential to cause injury. To evaluate the injury-causing potential of their
      refined ROB method using a lateral approach, the authors retrospectively reviewed
      ROB procedures carried out in their colony during an 18-month period and found
      that 0.6% of these procedures were associated with ocular injury. The authors
      also compared the quality of blood samples collected by ROB and by saphenous
      phlebotomy and found that ROB yielded samples of better quality. The authors
      conclude that, when done using a lateral approach and by an experienced
      technician, ROB is humane and safe and provides blood samples of adequate volume
      and quality for analysis. 

PMID- 24451362
TI  - Training tools from ASTD.

PMID- 24451363
TI  - The slippery slopes with Tommy, Kiko, Hercules, Leo and Duke.

PMID- 24451364
TI  - Apoptotic adipose-derived mesenchymal stem cell therapy protects against lung and
      kidney injury in sepsis syndrome caused by cecal ligation puncture in rats.
AB  - INTRODUCTION: We tested the hypothesis that apoptotic adipose-derived mesenchymal
      stem cells (A-ADMSC) are superior to healthy (H)-ADMSC in attenuating cecal
      ligation puncture (CLP)-induced sepsis-mediated lung and kidney injuries.
      METHODS: Adult male rats divided into group 1 (sham controls), group 2 (CLP),
      group 3 [CLP + H-ADMSC administered at 0.5, 6, and 18 hours after CLP], and group
      4 [CLP + A-ADMSC administered as in group 3] were sacrificed 72 hours after CLP
      with blood, lung, and kidney collected for studies. RESULTS: White blood cell
      (WBC) count, circulating TNF-alpha and creatinine levels were higher in groups 2
      and 3 than in groups 1 and 4 (all P < 0.001). Kidney and lung damage scores were
      highest in group 2, lowest in group 1, significantly higher in group 3 than in
      group 4 (all P < 0.0001). Protein expressions of inflammatory (ICAM-1, MMP-9, TNF
      alpha, NF-kappaB), oxidative, and apoptotic (Bax, caspase-3, PARP) biomarkers
      were higher in groups 2 and 3 than groups 1 and 4, whereas anti-apoptotic (Bcl-2)
      and mitochondrial integrity (cytochrome-C) biomarkers were lower in groups 2 and
      3 than in groups 1 and 4 (all P < 0.001). Expressions of anti-oxidant biomarkers
      at protein (GR, GPx, NQO-1, HO-1) and cellular (GR, GPx) levels were highest in
      group 4 (all P < 0.001). The number of inflammatory cells (CD3+) in lungs and
      levels of DNA damage marker (gamma-H2AX) in kidneys were higher in groups 2 and 3
      than in groups 1 and 4 (all P < 0.001). CONCLUSIONS: A-ADMSC therapy was superior
      to H-ADMSC therapy in protecting major organs from damage in rats with CLP
      induced sepsis syndrome.

PMID- 24451365
TI  - The effect of adding core stability training to a standard balance exercise
      program on sit to stand performance in older adults: a pilot study.
AB  - This study compared sit to stand (STS) performance between older adults in a nine
      week training program focusing on core stability exercises to enhance balance and
      postural control (EB) versus standard balance (SB) exercises. Repetitions in 30 s
      (STSreps) and kinematic performance (vertical and horizontal momentum, and margin
      of stability) were measured pre and postintervention in 23 older adults with at
      least one fall risk factor. Although both groups combined improved STSreps (P =
      .001) and vertical momentum (.008), a significant between-group difference was
      observed for completers only (MANCOVA of posttest group differences, with pretest
      scores as covariates; P = .04). EB demonstrated a greater but nonsignificant
      improvement in vertical momentum (P = .095). In conclusion, core stability
      training added to SB did not result in STS reps improvement. Compliance may
      modify these results and future larger sample studies should evaluate the impact
      of core stability training on STS biomechanics. 

PMID- 24451366
TI  - Multiphasic analysis of the temporal development of the distal gut microbiota in
      patients following ileal pouch anal anastomosis.
AB  - BACKGROUND: The indigenous gut microbiota are thought to play a crucial role in
      the development and maintenance of the abnormal inflammatory responses that are
      the hallmark of inflammatory bowel disease. Direct tests of the role of the gut
      microbiome in these disorders are typically limited by the fact that sampling of
      the microbiota generally occurs once disease has become manifest. This limitation
      could potentially be circumvented by studying patients who undergo total
      proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive
      treatment of ulcerative colitis. A subset of patients who undergo IPAA develops
      an inflammatory condition known as pouchitis, which is thought to mirror the
      pathogenesis of ulcerative colitis. Following the development of the microbiome
      of the pouch would allow characterization of the microbial community that
      predates the development of overt disease. RESULTS: We monitored the development
      of the pouch microbiota in four patients who underwent IPAA. Mucosal and luminal
      samples were obtained prior to takedown of the diverting ileostomy and compared
      to samples obtained 2, 4 and 8 weeks after intestinal continuity had been
      restored. Through the combined analysis of 16S rRNA-encoding gene amplicons,
      targeted 16S amplification and microbial cultivation, we observed major changes
      in structure and function of the pouch microbiota following ileostomy. There is a
      relative increase in anaerobic microorganisms with the capacity for fermentation
      of complex carbohydrates, which corresponds to the physical stasis of intestinal
      contents in the ileal pouch. Compared to the microbiome structure encountered in
      the colonic mucosa of healthy individuals, the pouch microbial community in three
      of the four individuals was quite distinct. In the fourth patient, a community
      that was much like that seen in a healthy colon was established, and this patient
      also had the most benign clinical course of the four patients, without the
      development of pouchitis 2 years after IPAA. CONCLUSIONS: The microbiota that
      inhabit the ileal-anal pouch of patients who undergo IPAA for treatment of
      ulcerative colitis demonstrate significant structural and functional changes
      related to the restoration of fecal flow. Our preliminary results suggest once
      the pouch has assumed the physiologic role previously played by the intact colon,
      the precise structure and function of the pouch microbiome, relative to a normal
      colonic microbiota, will determine if there is establishment of a stable, healthy
      mucosal environment or the reinitiation of the pathogenic cascade that results in
      intestinal inflammation.

PMID- 24451367
TI  - The Novel Secreted Adipokine WNT1-inducible Signaling Pathway Protein 2 (WISP2)
      Is a Mesenchymal Cell Activator of Canonical WNT.
AB  - WNT1-inducible-signaling pathway protein 2 (WISP2) is primarily expressed in
      mesenchymal stem cells, fibroblasts, and adipogenic precursor cells. It is both a
      secreted and cytosolic protein, the latter regulating precursor cell adipogenic
      commitment and PPARgamma induction by BMP4. To examine the effect of the secreted
      protein, we expressed a full-length and a truncated, non-secreted WISP2 in NIH3T3
      fibroblasts. Secreted, but not truncated WISP2 activated the canonical WNT
      pathway with increased beta-catenin levels, its nuclear targeting
      phosphorylation, and LRP5/6 phosphorylation. It also inhibited Pparg activation
      and the effect of secreted WISP2 was reversed by the WNT antagonist DICKKOPF-1.
      Differentiated 3T3-L1 adipose cells were also target cells where extracellular
      WISP2 activated the canonical WNT pathway, inhibited Pparg and associated adipose
      genes and, similar to WNT3a, promoted partial dedifferentiation of the cells and
      the induction of a myofibroblast phenotype with activation of markers of
      fibrosis. Thus, WISP2 exerts dual actions in mesenchymal precursor cells;
      secreted WISP2 activates canonical WNT and maintains the cells in an
      undifferentiated state, whereas cytosolic WISP2 regulates adipogenic commitment. 

PMID- 24451368
TI  - Myostatin induces insulin resistance via Casitas B-lineage lymphoma b (Cblb)
      mediated degradation of insulin receptor substrate 1 (IRS1) protein in response
      to high calorie diet intake.
AB  - To date a plethora of evidence has clearly demonstrated that continued high
      calorie intake leads to insulin resistance and type-2 diabetes with or without
      obesity. However, the necessary signals that initiate insulin resistance during
      high calorie intake remain largely unknown. Our results here show that in
      response to a regimen of high fat or high glucose diets, Mstn levels were induced
      in muscle and liver of mice. High glucose- or fat-mediated induction of Mstn was
      controlled at the level of transcription, as highly conserved carbohydrate
      response and sterol-responsive (E-box) elements were present in the Mstn promoter
      and were revealed to be critical for ChREBP (carbohydrate-responsive element
      binding protein) or SREBP1c (sterol regulatory element-binding protein 1c)
      regulation of Mstn expression. Further molecular analysis suggested that the
      increased Mstn levels (due to high glucose or fatty acid loading) resulted in
      increased expression of Cblb in a Smad3-dependent manner. Casitas B-lineage
      lymphoma b (Cblb) is an ubiquitin E3 ligase that has been shown to specifically
      degrade insulin receptor substrate 1 (IRS1) protein. Consistent with this, our
      results revealed that elevated Mstn levels specifically up-regulated Cblb,
      resulting in enhanced ubiquitin proteasome-mediated degradation of IRS1. In
      addition, over expression or knock down of Cblb had a major impact on IRS1 and
      pAkt levels in the presence or absence of insulin. Collectively, these
      observations strongly suggest that increased glucose levels and high fat diet,
      both, result in increased circulatory Mstn levels. The increased Mstn in turn is
      a potent inducer of insulin resistance by degrading IRS1 protein via the E3
      ligase, Cblb, in a Smad3-dependent manner.

PMID- 24451369
TI  - Shear stress-induced redistribution of vascular endothelial-protein-tyrosine
      phosphatase (VE-PTP) in endothelial cells and its role in cell elongation.
AB  - Vascular endothelial cells (ECs) are continuously exposed to shear stress (SS)
      generated by blood flow. Such stress plays a key role in regulation of various
      aspects of EC function including cell proliferation and motility as well as
      changes in cell morphology. Vascular endothelial-protein-tyrosine phosphatase (VE
      PTP) is an R3-subtype PTP that possesses multiple fibronectin type III-like
      domains in its extracellular region and is expressed specifically in ECs. The
      role of VE-PTP in EC responses to SS has remained unknown, however. Here we show
      that VE-PTP is diffusely localized in ECs maintained under static culture
      conditions, whereas it undergoes rapid accumulation at the downstream edge of the
      cells relative to the direction of flow in response to SS. This redistribution of
      VE-PTP triggered by SS was found to require its extracellular and transmembrane
      regions and was promoted by integrin engagement of extracellular matrix ligands.
      Inhibition of actin polymerization or of Cdc42, Rab5, or Arf6 activities
      attenuated the SS-induced redistribution of VE-PTP. VE-PTP also underwent
      endocytosis in the static and SS conditions. SS induced the polarized
      distribution of internalized VE-PTP. Such an effect was promoted by integrin
      engagement of fibronectin but prevented by inhibition of Cdc42 activity or of
      actin polymerization. In addition, depletion of VE-PTP by RNA interference in
      human umbilical vein ECs blocked cell elongation in the direction of flow induced
      by SS. Our results suggest that the polarized redistribution of VE-PTP in
      response to SS plays an important role in the regulation of EC function by blood
      flow. 

PMID- 24451370
TI  - Endocytosis and vacuolar degradation of the yeast cell surface glucose sensors
      Rgt2 and Snf3.
AB  - Sensing and signaling the presence of extracellular glucose is crucial for the
      yeast Saccharomyces cerevisiae because of its fermentative metabolism,
      characterized by high glucose flux through glycolysis. The yeast senses glucose
      through the cell surface glucose sensors Rgt2 and Snf3, which serve as glucose
      receptors that generate the signal for induction of genes involved in glucose
      uptake and metabolism. Rgt2 and Snf3 detect high and low glucose concentrations,
      respectively, perhaps because of their different affinities for glucose. Here, we
      provide evidence that cell surface levels of glucose sensors are regulated by
      ubiquitination and degradation. The glucose sensors are removed from the plasma
      membrane through endocytosis and targeted to the vacuole for degradation upon
      glucose depletion. The turnover of the glucose sensors is inhibited in
      endocytosis defective mutants, and the sensor proteins with a mutation at their
      putative ubiquitin-acceptor lysine residues are resistant to degradation. Of
      note, the low affinity glucose sensor Rgt2 remains stable only in high glucose
      grown cells, and the high affinity glucose sensor Snf3 is stable only in cells
      grown in low glucose. In addition, constitutively active, signaling forms of
      glucose sensors do not undergo endocytosis, whereas signaling defective sensors
      are constitutively targeted for degradation, suggesting that the stability of the
      glucose sensors may be associated with their ability to sense glucose. Therefore,
      our findings demonstrate that the amount of glucose available dictates the cell
      surface levels of the glucose sensors and that the regulation of glucose sensors
      by glucose concentration may enable yeast cells to maintain glucose sensing
      activity at the cell surface over a wide range of glucose concentrations. 

PMID- 24451371
TI  - CD226 protein is involved in immune synapse formation and triggers Natural Killer
      (NK) cell activation via its first extracellular domain.
AB  - CD226, an activating receptor that interacts with the ligands CD155 and CD112,
      activates natural killer (NK) cells via its immunoreceptor tyrosine-based
      activatory motif (ITAM). There are two extracellular domains of CD226; however,
      the comparative functional relevance of these domains remains unknown. In this
      study, two different deletion mutants, rCD226-ECD1 (the first extracellular
      domain) and rCD226-ECD (full extracellular domains), were recombinantly
      expressed. We observed that rCD226-ECD1, similar to rCD226-ECD, specifically
      bound to ligand-positive cell lines and that this interaction could be
      competitively blocked by an anti-CD226 mAb. In addition, rCD226-ECD1 was able to
      block the binding of CD112 mAb to tumor cells in a competitive binding assay.
      Importantly, based on surface plasmon resonance (SPR), we determined that rCD226
      ECD1, similar to rCD226-ECD, directly bound to its ligand CD155 on a protein
      chip. Functionally, NK cell cytotoxicity against K562 or HeLa cells was blocked
      by rCD226-ECD1 by reducing the expression of CD69 and granzyme B, indicating the
      critical role of ECD1 in NK cell activation. We also examined the role of rCD226
      ECD1 in effector/target interactions by using rCD226-ECD to block these
      interactions. Using flow cytometry, we found that the number of conjugates
      between IL-2-dependent NKL cells and HeLa cells was reduced and observed that the
      formation of immune synapses was also decreased under confocal microscopy. In
      addition, we prepared two anti-rCD226-ECD1 agonistic antibodies, 2E6 and 3B9.
      Both 2E6 and 3B9 antibodies could induce the phosphorylation of ERK in NK-92
      cells. Taken together, our results show that CD226 functions via its first
      extracellular domain. 

PMID- 24451372
TI  - Histone deacetylase 2 (HDAC2) protein-dependent deacetylation of mortality factor
      4-like 1 (MORF4L1) protein enhances its homodimerization.
AB  - Histone acetyltransferase mortality factor 4-like 1 (MORF4L1) is a relatively new
      histone acetyltransferase component that exists as a homodimer to exert its
      epigenetic function. The mechanism of MORF4L1 self-assembly is unknown. Here we
      report that Lys-148 deacetylation is indispensable for facilitating MORF4L1 self
      assembly into a homodimeric unit. Among a stretch of ~10 amino acids in the NH2
      terminus between the chromodomain and MORF4-related gene (MRG) domain within
      MORF4L1, Lys-148 is normally acetylated. Substitution of Lys-148 with arginine
      augments MORF4L1 self-assembly. However, acetylation mimics of MORF4L1, including
      K148L and K148Q, abolished its self-assembly of the histone acetyltransferase
      component. HDAC2, a deacetylase, interacts with and keeps MORF4L1 in a
      deacetylation status at Lys(148) that triggers MORF4L1 self-assembly. Knockdown
      of HDAC2 reduces MORF4L1 self-assembly. HDAC2-dependent deacetylation of MORF4L1
      enhances MORF4L1 homodimerization, thus facilitating the functionality of complex
      formation to repress cell proliferation. 

PMID- 24451373
TI  - p53 protein regulates Hsp90 ATPase activity and thereby Wnt signaling by
      modulating Aha1 expression.
AB  - The p53 tumor suppressor gene encodes a homotetrameric transcription factor which
      is activated in response to a variety of cellular stressors, including DNA damage
      and oncogene activation. p53 mutations occur in >50% of human cancers. Although
      p53 has been shown to regulate Wnt signaling, the underlying mechanisms are not
      well understood. Here we show that silencing p53 in colon cancer cells led to
      increased expression of Aha1, a co-chaperone of Hsp90. Heat shock factor-1 was
      important for mediating the changes in Aha1 levels. Increased Aha1 levels were
      associated with enhanced interactions with Hsp90, resulting in increased Hsp90
      ATPase activity. Moreover, increased Hsp90 ATPase activity resulted in increased
      phosphorylation of Akt and glycogen synthase kinase-3beta (GSK3beta), leading to
      enhanced expression of Wnt target genes. Significantly, levels of Aha1, Hsp90
      ATPase activity, Akt, and GSK3beta phosphorylation and expression of Wnt target
      genes were increased in the colons of p53-null as compared with p53 wild type
      mice. Using p53 heterozygous mutant epithelial cells from Li-Fraumeni syndrome
      patients, we show that a monoallelic mutation of p53 was sufficient to activate
      the Aha1/Hsp90 ATPase axis leading to stimulation of Wnt signaling and increased
      expression of Wnt target genes. Pharmacologic intervention with CP-31398, a p53
      rescue agent, inhibited recruitment of Aha1 to Hsp90 and suppressed Wnt-mediated
      gene expression in colon cancer cells. Taken together, this study provides new
      insights into the mechanism by which p53 regulates Wnt signaling and raises the
      intriguing possibility that p53 status may affect the efficacy of anticancer
      therapies targeting Hsp90 ATPase. 

PMID- 24451374
TI  - Vaccinia viral protein A27 is anchored to the viral membrane via a cooperative
      interaction with viral membrane protein A17.
AB  - The vaccinia viral protein A27 in mature viruses specifically interacts with
      heparan sulfate for cell surface attachment. In addition, A27 associates with the
      viral membrane protein A17 to anchor to the viral membrane; however, the specific
      interaction between A27 and A17 remains largely unclear. To uncover the active
      binding sites and the underlying binding mechanism, we expressed and purified the
      N-terminal (18-50 residues) and C-terminal (162-203 residues) fragments of A17,
      which are denoted A17-N and A17-C. Through surface plasmon resonance, the binding
      affinity of A27/A17-N (KA = 3.40 * 10(8) m(-1)) was determined to be
      approximately 3 orders of magnitude stronger than that of A27/A17-C (KA = 3.40 *
      10(5) m(-1)), indicating that A27 prefers to interact with A17-N rather than A17
      C. Despite the disordered nature of A17-N, the A27-A17 interaction is mediated by
      a specific and cooperative binding mechanism that includes two active binding
      sites, namely (32)SFMPK(36) (denoted as F1 binding) and (20)LDKDLFTEEQ(29) (F2).
      Further analysis showed that F1 has stronger binding affinity and is more
      resistant to acidic conditions than is F2. Furthermore, A27 mutant proteins that
      retained partial activity to interact with the F1 and F2 sites of the A17 protein
      were packaged into mature virus particles at a reduced level, demonstrating that
      the F1/F2 interaction plays a critical role in vivo. Using these results in
      combination with site-directed mutagenesis data, we established a computer model
      to explain the specific A27-A17 binding mechanism. 

PMID- 24451375
TI  - Induction of Gsk3beta-beta-TrCP interaction is required for late phase
      stabilization of beta-catenin in canonical Wnt signaling.
AB  - A pivotal step in canonical Wnt signaling is Wnt-induced beta-catenin
      stabilization. In the absence of Wnt, beta-catenin is targeted for beta
      transducin repeats-containing proteins (beta-TrCP)-mediated degradation due to
      phosphorylation by glycogen synthase kinase 3 (Gsk3). How canonical Wnt signaling
      regulates Gsk3 to inhibit beta-catenin proteolysis remains largely elusive. This
      study reveals novel key molecular events in Wnt signaling: induction of Gsk3beta
      ubiquitination and Gsk3beta-beta-TrCP binding. We found that Wnt stimulation
      induced prolonged monoubiquitination of Gsk3beta and Gsk3beta-beta-TrCP
      interaction. Monoubiquitination did not cause Gsk3beta degradation nor affects
      its enzymatic activity. Rather, increased monoubiquitination of Gsk3beta/Gsk3beta
      beta-TrCP association suppressed beta-catenin recruitment of beta-TrCP, leading
      to long-term inhibition of beta-catenin ubiquitination and degradation. 

PMID- 24451376
TI  - The carboxyl terminus of FANCE recruits FANCD2 to the Fanconi Anemia (FA) E3
      ligase complex to promote the FA DNA repair pathway.
AB  - Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow
      failure and cellular hypersensitivity to DNA cross-linking agents. In response to
      DNA damage, the FA pathway is activated through the cooperation of 16 FA
      proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase
      complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and
      FANCI. FANCE, a subunit of the FA core complex, plays an essential role by
      promoting the integrity of the complex and by directly recognizing FANCD2. To
      delineate its role in substrate ubiquitination from the core complex assembly, we
      analyzed a series of mutations within FANCE. We report that a phenylalanine
      located at the highly conserved extreme C terminus, referred to as Phe-522, is a
      critical residue for mediating the monoubiquitination of the FANCD2-FANCI
      complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2
      interaction as a tool, we found that the interaction-deficient mutant conferred
      cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree
      as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction
      in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE
      C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating
      the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair. 

PMID- 24451377
TI  - The Chinese herb isolate yuanhuacine (YHL-14) induces G2/M arrest in human cancer
      cells by up-regulating p21 protein expression through an p53 protein-independent
      cascade.
AB  - Yuanhuacine (YHL-14), the major component of daphnane diterpene ester isolated
      from the flower buds of Daphne genkwa, has been reported to have activity against
      cell proliferation in various cancer cell lines. Nevertheless, the potential
      mechanism has not been explored yet. Here we demonstrate that YHL-14 inhibits
      bladder and colon cancer cell growth through up-regulation of p21 expression in
      an Sp1-dependent manner. We found that YHL-14 treatment resulted in up-regulation
      of p21 expression and a significant G2/M phase arrest in T24T and HCT116 cells
      without affecting p53 protein expression and activation. Further studies indicate
      that p21 induction by YHL-14 occurs at the transcriptional level via up
      regulation of Sp1 protein expression. Moreover, our results show that p38 is
      essential for YHL-14-mediated Sp1 protein stabilization, G2/M growth arrest
      induction, and anchorage-independent growth inhibition of cancer cells. Taken
      together, our studies demonstrate a novel mechanism of YHL-14 against cancer cell
      growth in bladder and colon cancer cell lines, which provides valuable
      information for the design and synthesis of other new conformation-constrained
      derivatives on the basis of the structure of YHL-14 for cancer therapy. 

PMID- 24451378
TI  - Histone deacetylase inhibitors modulate the transcriptional regulation of
      guanylyl cyclase/natriuretic peptide receptor-a gene: interactive roles of
      modified histones, histone acetyltransferase, p300, AND Sp1.
AB  - Atrial natriuretic peptide (ANP) binds guanylyl cyclase-A/natriuretic peptide
      receptor-A (GC-A/NPRA) and produces the intracellular second messenger, cGMP,
      which regulates cardiovascular homeostasis. We sought to determine the function
      of histone deacetylases (HDACs) in regulating Npr1 (coding for GC-A/NPRA) gene
      transcription, using primary mouse mesangial cells treated with class-specific
      HDAC inhibitors (HDACi). Trichostatin A, a pan inhibitor, and mocetinostat
      (MGCD0103), a class I HDAC inhibitor, significantly enhanced Npr1 promoter
      activity (by 8- and 10-fold, respectively), mRNA levels (4- and 5.3-fold,
      respectively), and NPRA protein (2.7- and 3.5-fold, respectively). However,
      MC1568 (class II HDAC inhibitor) had no discernible effect. Overexpression of
      HDAC1 and HDAC2 significantly attenuated Npr1 promoter activity, whereas HDAC3
      and HDAC8 had no effect. HDACi-treated cultured cells in vitro and intact animals
      in vivo showed significantly reduced binding of HDAC1 and -2 and increased
      accumulation of acetylated H3-K9/14 and H4-K12 at the Npr1 promoter. Deletional
      analyses of the Npr1 promoter along with ectopic overexpression and inhibition of
      Sp1 confirmed that HDACi-induced Npr1 gene transcription is accomplished by Sp1
      activation. Furthermore, HDACi attenuated the interaction of Sp1 with HDAC1/2 and
      promoted Sp1 association with p300 and p300/cAMP-binding protein-associated
      factor; it also promoted the recruitment of p300 and p300/cAMP-binding protein
      associated factor to the Npr1 promoter. Our results demonstrate that trichostatin
      A and MGCD0103 enhanced Npr1 gene expression through inhibition of HDAC1/2 and
      increased both acetylation of histones (H3-K9/14, H4-K12) and Sp1 by p300, and
      their recruitment to Npr1 promoter. Our findings define a novel epigenetic
      regulatory mechanism that governs Npr1 gene transcription. 

PMID- 24451379
TI  - Characterization of all family-9 glycoside hydrolases synthesized by the
      cellulosome-producing bacterium Clostridium cellulolyticum.
AB  - The genome of Clostridium cellulolyticum encodes 13 GH9 enzymes that display
      seven distinct domain organizations. All but one contain a dockerin module and
      were formerly detected in the cellulosomes, but only three of them were
      previously studied (Cel9E, Cel9G, and Cel9M). In this study, the 10
      uncharacterized GH9 enzymes were overproduced in Escherichia coli and purified,
      and their activity pattern was investigated in the free state or in cellulosome
      chimeras with key cellulosomal cellulases. The newly purified GH9 enzymes,
      including those that share similar organization, all exhibited distinct activity
      patterns, various binding capacities on cellulosic substrates, and different
      synergies with pivotal cellulases in mini-cellulosomes. Furthermore, one enzyme
      (Cel9X) was characterized as the first genuine endoxyloglucanase belonging to
      this family, with no activity on soluble and insoluble celluloses. Another GH9
      enzyme (Cel9V), whose sequence is 78% identical to the cellulosomal cellulase
      Cel9E, was found inactive in the free and complexed states on all tested
      substrates. The sole noncellulosomal GH9 (Cel9W) is a cellulase displaying a
      broad substrate specificity, whose engineered form bearing a dockerin can act
      synergistically in minicomplexes. Finally, incorporation of all GH9 cellulases in
      trivalent cellulosome chimera containing Cel48F and Cel9G generated a mixture of
      heterogeneous mini-cellulosomes that exhibit more activity on crystalline
      cellulose than the best homogeneous tri-functional complex. Altogether, our data
      emphasize the importance of GH9 diversity in bacterial cellulosomes, confirm that
      Cel9G is the most synergistic GH9 with the major endoprocessive cellulase Cel48F,
      but also identify Cel9U as an important cellulosomal component during cellulose
      depolymerization. 

PMID- 24451380
TI  - LT175 is a novel PPARalpha/gamma ligand with potent insulin-sensitizing effects
      and reduced adipogenic properties.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent
      transcription factors regulating lipid and glucose metabolism. Ongoing drug
      discovery programs aim to develop dual PPARalpha/gamma agonists devoid of the
      side effects of the marketed antidiabetic agents thiazolidinediones and the dual
      agonists glitazars. Recently, we described a new dual PPARalpha/gamma ligand,
      LT175, with a partial agonist profile against PPARgamma and interacting with a
      newly identified region of the PPARgamma-ligand binding domain (1). Here we show
      that LT175 differentially activated PPARgamma target genes involved in fatty acid
      esterification and storage in 3T3-L1-derived adipocytes. This resulted in a less
      severe lipid accumulation compared with that triggered by rosiglitazone,
      suggesting that LT175 may have a lower adipogenic activity. Consistent with this
      hypothesis, in vivo administration of LT175 to mice fed a high-fat diet decreased
      body weight, adipocyte size, and white adipose tissue mass, as assessed by
      magnetic resonance imaging. Furthermore, LT175 significantly reduced plasma
      glucose, insulin, non-esterified fatty acids, triglycerides, and cholesterol and
      increased circulating adiponectin and fibroblast growth factor 21 levels. Oral
      glucose and insulin tolerance tests showed that the compound improves glucose
      homeostasis and insulin sensitivity. Moreover, we demonstrate that the peculiar
      interaction of LT175 with PPARgamma affected the recruitment of the coregulators
      cyclic-AMP response element-binding protein-binding protein and nuclear
      corepressor 1 (NCoR1), fundamentals for the PPARgamma-mediated adipogenic
      program. In conclusion, our results describe a new PPAR ligand, modulating lipid
      and glucose metabolism with reduced adipogenic activity, that may be used as a
      model for a series of novel molecules with an improved pharmacological profile
      for the treatment of dyslipidemia and type 2 diabetes. 

PMID- 24451381
TI  - In situ dimerization of multiple wild type and mutant zinc transporters in live
      cells using bimolecular fluorescence complementation.
AB  - Zinc transporters (ZnTs) facilitate zinc efflux and zinc compartmentalization,
      thereby playing a key role in multiple physiological processes and pathological
      disorders, presumed to be modulated by transporter dimerization. We recently
      proposed that ZnT2 homodimerization is the underlying basis for the dominant
      negative effect of a novel heterozygous G87R mutation identified in women
      producing zinc-deficient milk. To provide direct visual evidence for the in situ
      dimerization and function of multiple normal and mutant ZnTs, we applied here the
      bimolecular fluorescence complementation (BiFC) technique, which enables direct
      visualization of specific protein-protein interactions. BiFC is based upon
      reconstitution of an intact fluorescent protein including YFP when its two
      complementary, non-fluorescent N- and C-terminal fragments (termed YN and YC) are
      brought together by a pair of specifically interacting proteins. Homodimerization
      of ZnT1, -2, -3, -4, and -7 was revealed by high subcellular fluorescence
      observed upon co-transfection of non-fluorescent ZnT-YC and ZnT-YN; this
      homodimer fluorescence localized in the characteristic compartments of each ZnT.
      The validity of the BiFC assay in ZnT dimerization was further corroborated when
      high fluorescence was obtained upon co-transfection of ZnT5-YC and ZnT6-YN, which
      are known to form heterodimers. We further show that BiFC recapitulated the
      pathogenic role that ZnT mutations play in transient neonatal zinc deficiency.
      Zinquin, a fluorescent zinc probe applied along with BiFC, revealed the in situ
      functionality of ZnT dimers. Hence, the current BiFC-Zinquin technique provides
      the first in situ evidence for the dimerization and function of wild type and
      mutant ZnTs in live cells. 

PMID- 24451383
TI  - Molecular motions involved in Na-K-Cl cotransporter-mediated ion transport and
      transporter activation revealed by internal cross-linking between transmembrane
      domains 10 and 11/12.
AB  - We examined the relationship between transmembrane domain (TM) 10 and TM11/12 in
      NKCC1, testing homology models based on the structure of AdiC in the same
      transporter superfamily. We hypothesized that introduced cysteine pairs would be
      close enough for disulfide formation and would alter transport function: indeed,
      evidence for cross-link formation with low micromolar concentrations of copper
      phenanthroline or iodine was found in 3 of 8 initially tested pairs and in 1 of
      26 additionally tested pairs. Inhibition of transport was observed with copper
      phenanthroline and iodine treatment of P676C/A734C and I677C/A734C, consistent
      with the proximity of these residues and with movement of TM10 during the
      occlusion step of ion transport. We also found Cu(2+) inhibition of the single
      cysteine mutant A675C, suggesting that this residue and Met(382) of TM3 are
      involved in a Cu(2+)-binding site. Surprisingly, cross-linking of P676C/I730C was
      found to prevent rapid deactivation of the transporter while not affecting the
      dephosphorylation rate, thus uncoupling the phosphorylation and activation steps.
      Consistent with this, (a) cross-linking of P676C/I730C was dependent on
      activation state, and (b) mutants lacking the phosphoregulatory domain could
      still be activated by cross-linking. These results suggest a model of NKCC
      activation that involves movement of TM12 relative to TM10, which is likely tied
      to movement of the large C terminus, a process somehow triggered by
      phosphorylation of the regulatory domain in the N terminus. 

PMID- 24451382
TI  - A redox-resistant sirtuin-1 mutant protects against hepatic metabolic and oxidant
      stress.
AB  - Sirtuin-1 (SirT1), a member of the NAD(+)-dependent class III histone deacetylase
      family, is inactivated in vitro by oxidation of critical cysteine thiols. In a
      model of metabolic syndrome, SirT1 activation attenuated apoptosis of hepatocytes
      and improved liver function including lipid metabolism. We show in SirT1
      overexpressing HepG2 cells that oxidants (nitrosocysteine and hydrogen peroxide)
      or metabolic stress (high palmitate and high glucose) inactivated SirT1 by
      reversible oxidative post-translational modifications (OPTMs) on three cysteines.
      Mutating these oxidation-sensitive cysteines to serine preserved SirT1 activity
      and abolished reversible OPTMs. Overexpressed mutant SirT1 maintained deacetylase
      activity and attenuated proapoptotic signaling, whereas overexpressed wild type
      SirT1 was less protective in metabolically or oxidant-stressed cells. To prove
      that OPTMs of SirT1 are glutathione (GSH) adducts, glutaredoxin-1 was
      overexpressed to remove this modification. Glutaredoxin-1 overexpression
      maintained endogenous SirT1 activity and prevented proapoptotic signaling in
      metabolically stressed HepG2 cells. The in vivo significance of oxidative
      inactivation of SirT1 was investigated in livers of high fat diet-fed C57/B6J
      mice. SirT1 deacetylase activity was decreased in the absence of changes in SirT1
      expression and associated with a marked increase in OPTMs. These results indicate
      that glutathione adducts on specific SirT1 thiols may be responsible for
      dysfunctional SirT1 associated with liver disease in metabolic syndrome. 

PMID- 24451385
TI  - Rate and extent NOM removal during oxidation and biofiltration.
AB  - The presence of natural organic matter (NOM) in drinking water treatment presents
      many challenges. Integrated treatment processes combining oxidation and
      biofiltration have been demonstrated to be very effective at reducing NOM,
      specifically biodegradable organics. Laboratory bench-scale experiments were
      carried out to investigate the effect of oxidation by ozonation or UV/H2O2 on
      NOM. Specifically the rate of biodegradation was studied by performing bench
      scale biodegradation experiments using acclimatized biological activated carbon
      (BAC). For the source water investigated, oxidation did not preferentially react
      with the biodegradable or non-biodegradable NOM. In addition, the type or dose of
      oxidation applied did not affect the observed rate of biodegradation. The rate
      kinetics for biodegradation were constant for all oxidation conditions
      investigated. Oxidation prior to biofiltration increased the overall removal of
      organic matter, but did not affect the rate of biodegradation of NOM. 

PMID- 24451384
TI  - Inherent regulation of EAL domain-catalyzed hydrolysis of second messenger cyclic
      di-GMP.
AB  - The universal second messenger cyclic di-GMP (cdG) is involved in the regulation
      of a diverse range of cellular processes in bacteria. The intracellular
      concentration of the dinucleotide is determined by the opposing actions of
      diguanylate cyclases and cdG-specific phosphodiesterases (PDEs). Whereas most
      PDEs have accessory domains that are involved in the regulation of their
      activity, the regulatory mechanism of this class of enzymes has remained unclear.
      Here, we use biophysical and functional analyses to show that the isolated EAL
      domain of a PDE from Escherichia coli (YahA) is in a fast thermodynamic monomer
      dimer equilibrium, and that the domain is active only in its dimeric state.
      Furthermore, our data indicate thermodynamic coupling between substrate binding
      and EAL dimerization with the dimerization affinity being increased about 100
      fold upon substrate binding. Crystal structures of the YahA-EAL domain determined
      under various conditions (apo, Mg(2+), cdG.Ca(2+) complex) confirm structural
      coupling between the dimer interface and the catalytic center. The built-in
      regulatory properties of the EAL domain probably facilitate its modular,
      functional combination with the diverse repertoire of accessory domains. 

PMID- 24451386
TI  - Endothelial mineralocorticoid receptor activation enhances endothelial protein C
      receptor and decreases vascular thrombosis in mice.
AB  - Previous studies have shown that aldosterone, which activates the
      mineralocorticoid receptor (MR), promotes thrombosis in animal models. Our
      objective was to determine whether MR activation/expression in the vascular
      endothelium could modify thrombotic risk in vivo and to examine thrombin
      generation at the surface of aortic endothelial cells (HAECs). MR was
      conditionally overexpressed in vivo in vascular endothelial cells in mice (MR-EC
      mice) or stimulated with aldosterone in HAECs. Thrombosis after ferric chloride
      injury was delayed in MR-EC mice compared with controls as well as in wild-type
      FVB/NRj mice treated with aldosterone (60 MUg/kg/d for 21 d). Thrombin generation
      in platelet-poor plasma did not differ between MR-EC mice and controls. In MR-EC
      mice, aortic endothelial cell protein C receptor (EPCR) expression was increased.
      Aldosterone (10(-8) M) attenuated thrombin generation at the surface of cultured
      HAECs, and this effect was associated with up-regulation of expression of EPCR,
      which promotes formation of activated protein C. Aldosterone increases EPCR
      expression via a transcriptional mechanism involving interaction of MR with the
      specificity protein 1 site. These findings demonstrate that MR activation acts on
      endothelial cells to protect against thrombosis in physiological conditions and
      that MR-mediated EPCR overexpression drives this antithrombotic property through
      enhancing protein C activation.

PMID- 24451387
TI  - Nedd4-2 regulates surface expression and may affect N-glycosylation of
      hyperpolarization-activated cyclic nucleotide-gated (HCN)-1 channels.
AB  - HCN channels are important regulators of neuronal excitability. The proper
      function of these channels is governed by various mechanisms, including post
      translational modifications of channel subunits. Here, we provide evidence that
      ubiquitination via a ubiquitin ligase, neuronal precursor cell expressed
      developmentally downregulated (Nedd)-4-2, is involved in the regulation of
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. We identified
      a PY motif (L/PPxY), the characteristic binding motif for Nedd4-2 in the C
      terminus of the HCN1 subunit, and showed that HCN1 and Nedd4-2 interacted both in
      vivo (rat hippocampus, neocortex, and cerebellum) and in vitro [human embryonic
      kidney 293 (HEK293) cells], resulting in increased HCN1 ubiquitination.
      Elimination of the PY motif reduced, but did not abolish, Nedd4-2 binding, which
      further involved a stretch of ~100 aa downstream in the HCN1 C terminus.
      Coexpression of Nedd4-2 and HCN1 drastically reduced the HCN1-mediated h-current
      amplitude (85-92%) in Xenopus laevis oocytes and reduced surface expression (34%)
      of HCN1 channels in HEK293 cells, thereby opposing effects of tetratricopeptide
      repeat-containing Rab8b interacting protein (TRIP8b)-(1a-4), an auxiliary subunit
      that promotes HCN1 surface expression. Regulation may further include N
      glycosylation of HCN1 channels, which is significantly enhanced by TRIP8b(1a-4),
      but may be reduced by Nedd4-2. Taken together, our data indicate that Nedd4-2
      plays an important role in the regulation of HCN1 trafficking and may compete
      with TRIP8b(1a-4) in this process.

PMID- 24451388
TI  - FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during
      ovarian development in mice.
AB  - Steroidogenic factor 1 (SF1; Ad4BP/NR5A1) plays key roles in gonadal development.
      Initially, the Sf1 gene is expressed in mouse fetal gonads of both sexes, but
      later is up-regulated in testes and down-regulated in ovaries. While Sf1
      expression is activated and maintained by Wilms tumor 1 (WT1) and LIM homeobox 9
      (LHX9), the mechanism of sex-specific regulation remains unclear. We hypothesized
      that Sf1 is repressed by the transcription factor Forkhead box L2 (FOXL2) during
      ovarian development. In an in vitro system (TM3 cells), up-regulation of Sf1 by
      the WT1 splice variant WT1-KTS was antagonized by FOXL2, as determined by
      quantitative RT-PCR. Using reporter assays, we localized the Sf1 proximal
      promoter region involved in this antagonism to a 674-bp interval. A conserved
      FOXL2 binding site was identified in this interval by in vitro chromatin
      immunoprecipitation. Introducing mutations into this site abolished negative
      regulation by FOXL2 in reporter assays. Finally, in Foxl2-null mice, Sf1
      expression was increased 2-fold relative to wild-type XX fetal gonads. Our
      results support the hypothesis that FOXL2 negatively regulates Sf1 expression by
      antagonizing WT1-KTS during early ovarian development in mice.

PMID- 24451389
TI  - Predicting connectivity of green turtles at Palmyra Atoll, central Pacific: a
      focus on mtDNA and dispersal modelling.
AB  - Population connectivity and spatial distribution are fundamentally related to
      ecology, evolution and behaviour. Here, we combined powerful genetic analysis
      with simulations of particle dispersal in a high-resolution ocean circulation
      model to investigate the distribution of green turtles foraging at the remote
      Palmyra Atoll National Wildlife Refuge, central Pacific. We analysed
      mitochondrial sequences from turtles (n = 349) collected there over 5 years (2008
      2012). Genetic analysis assigned natal origins almost exclusively (approx. 97%)
      to the West Central and South Central Pacific combined Regional Management Units.
      Further, our modelling results indicated that turtles could potentially drift
      from rookeries to Palmyra Atoll via surface currents along a near-Equatorial
      swathe traversing the Pacific. Comparing findings from genetics and modelling
      highlighted the complex impacts of ocean currents and behaviour on natal origins.
      Although the Palmyra feeding ground was highly differentiated genetically from
      others in the Indo-Pacific, there was no significant differentiation among years,
      sexes or stage-classes at the Refuge. Understanding the distribution of this
      foraging population advances knowledge of green turtles and contributes to
      effective conservation planning for this threatened species.

PMID- 24451390
TI  - Spatio-temporal skin strain distributions evoke low variability spike responses
      in cuneate neurons.
AB  - A common method to explore the somatosensory function of the brain is to relate
      skin stimuli to neurophysiological recordings. However, interaction with the skin
      involves complex mechanical effects. Variability in mechanically induced spike
      responses is likely to be due in part to mechanical variability of the
      transformation of stimuli into spiking patterns in the primary sensors located in
      the skin. This source of variability greatly hampers detailed investigations of
      the response of the brain to different types of mechanical stimuli. A novel
      stimulation technique designed to minimize the uncertainty in the strain
      distributions induced in the skin was applied to evoke responses in single
      neurons in the cat. We show that exposure to specific spatio-temporal stimuli
      induced highly reproducible spike responses in the cells of the cuneate nucleus,
      which represents the first stage of integration of peripheral inputs to the
      brain. Using precisely controlled spatio-temporal stimuli, we also show that
      cuneate neurons, as a whole, were selectively sensitive to the spatial and to the
      temporal aspects of the stimuli. We conclude that the present skin stimulation
      technique based on localized differential tractions greatly reduces response
      variability that is exogenous to the information processing of the brain and
      hence paves the way for substantially more detailed investigations of the brain's
      somatosensory system. 

PMID- 24451391
TI  - Re-epithelialization: advancing epithelium frontier during wound healing.
AB  - The first function of the skin is to serve as a protective barrier against the
      environment. Its loss of integrity as a result of injury or illness may lead to a
      major disability and the first goal of healing is wound closure involving many
      biological processes for repair and tissue regeneration. In vivo wound healing
      has four phases, one of them being the migration of the healthy epithelium
      surrounding the wound in the direction of the injury in order to cover it. Here,
      we present a theoretical model of the re-epithelialization phase driven by
      chemotaxis for a circular wound. This model takes into account the diffusion of
      chemoattractants both in the wound and the neighbouring tissue, the uptake of
      these molecules by the surface receptors of epithelial cells, the migration of
      the neighbour epithelium, the tension and proliferation at the wound border.
      Using a simple Darcy's law for cell migration transforms our biological model
      into a free-boundary problem, which is analysed in the simplified circular
      geometry leading to explicit solutions for the closure and making stability
      analysis possible. It turns out that for realistic wound sizes of the order of
      centimetres and from experimental data, the re-epithelialization is always an
      unstable process and the perfect circle cannot be observed, a result confirmed by
      fully nonlinear simulations and in agreement with experimental observations. 

PMID- 24451392
TI  - Improving controllable adhesion on both rough and smooth surfaces with a hybrid
      electrostatic/gecko-like adhesive.
AB  - This paper describes a novel, controllable adhesive that combines the benefits of
      electrostatic adhesives with gecko-like directional dry adhesives. When working
      in combination, the two technologies create a positive feedback cycle whose
      adhesion, depending on the surface type, is often greater than the sum of its
      parts. The directional dry adhesive brings the electrostatic adhesive closer to
      the surface, increasing its effect. Similarly, the electrostatic adhesion helps
      engage more of the directional dry adhesive fibrillar structures, particularly on
      rough surfaces. This paper presents the new hybrid adhesive's manufacturing
      process and compares its performance to three other adhesive technologies
      manufactured using a similar process: reinforced PDMS, electrostatic and
      directional dry adhesion. Tests were performed on a set of ceramic tiles with
      varying roughness to quantify its effect on shear adhesive force. The relative
      effectiveness of the hybrid adhesive increases as the surface roughness is
      increased. Experimental data are also presented for different substrate materials
      to demonstrate the enhanced performance achieved with the hybrid adhesive.
      Results show that the hybrid adhesive provides up to 5.1* greater adhesion than
      the electrostatic adhesive or directional dry adhesive technologies alone.

PMID- 24451393
TI  - Computer-assisted design for scaling up systems based on DNA reaction networks.
AB  - In the past few years, there have been many exciting advances in the field of
      molecular programming, reaching a point where implementation of non-trivial
      systems, such as neural networks or switchable bistable networks, is a reality.
      Such systems require nonlinearity, be it through signal amplification,
      digitalization or the generation of autonomous dynamics such as oscillations. The
      biochemistry of DNA systems provides such mechanisms, but assembling them in a
      constructive manner is still a difficult and sometimes counterintuitive process.
      Moreover, realistic prediction of the actual evolution of concentrations over
      time requires a number of side reactions, such as leaks, cross-talks or
      competitive interactions, to be taken into account. In this case, the design of a
      system targeting a given function takes much trial and error before the correct
      architecture can be found. To speed up this process, we have created DNA
      Artificial Circuits Computer-Assisted Design (DACCAD), a computer-assisted design
      software that supports the construction of systems for the DNA toolbox. DACCAD is
      ultimately aimed to design actual in vitro implementations, which is made
      possible by building on the experimental knowledge available on the DNA toolbox.
      We illustrate its effectiveness by designing various systems, from Montagne et
      al.'s Oligator or Padirac et al.'s bistable system to new and complex networks,
      including a two-bit counter or a frequency divider as well as an example of very
      large system encoding the game Mastermind. In the process, we highlight a variety
      of behaviours, such as enzymatic saturation and load effect, which would be hard
      to handle or even predict with a simpler model. We also show that those
      mechanisms, while generally seen as detrimental, can be used in a positive way,
      as functional part of a design. Additionally, the number of parameters included
      in these simulations can be large, especially in the case of complex systems. For
      this reason, we included the possibility to use CMA-ES, a state-of-the-art
      optimization algorithm that will automatically evolve parameters chosen by the
      user to try to match a specified behaviour. Finally, because all possible
      functionality cannot be captured by a single software, DACCAD includes the
      possibility to export a system in the synthetic biology markup language, a widely
      used language for describing biological reaction systems. DACCAD can be
      downloaded online at http://www.yannick-rondelez.com/downloads/.

PMID- 24451394
TI  - Synthesising periodic triggering signals with genetic oscillators.
AB  - The potential of the clock lies in its role of triggering logic reaction for
      sequential biological circuits. This research introduces an idea of designing a
      genetic clock generator by Fourier series based on the genetic oscillators. The
      authors generalise the design idea using a combination of fundamental sinusoidal
      signals. Since biochemical reaction of the biological system is extremely slow,
      however, transition between minimal and maximal levels is instantaneous for an
      ideal clock signal; it is thus not directly realisable in biological systems.
      That means it would be hard to directly synthesize a square wave generator for
      use as a genetic clock. They apply Fourier series to represent a square wave as a
      finite summation of sinusoidal waves generated by some genetic oscillators with
      different harmonic oscillating frequencies, in which the amplitude alternates at
      a constant frequency between the fixed minimal and maximal levels with the same
      duration of time. 

PMID- 24451395
TI  - On the design of human immunodeficiency virus treatment based on a non-linear
      time-delay model.
AB  - Mathematical modelling and methods from control theory can be employed to find
      appropriate drug regimens in human immunodeficiency virus (HIV) treatment. In
      this study, using a non-linear time-delay model, the authors design some
      suboptimal highly active antiretroviral therapy (HAART)
      [http://www.en.wikipedia.org/wiki/Protease_inhibitor_%28pharmacology%29] regimens
      for patients with HIV. The non-linear delayed model is used to describe the
      dynamical interactions between HIV and human immune system in the presence of
      HAART. Based on the model, a set point tracking problem is defined in order to
      set the number of susceptible CD4+T cells to a desired value. To solve this set
      point tracking problem in a suboptimal way, the authors introduce a new method
      which is able to consider constraints on the amount of drug dosage. It is proved
      that the proposed method is able to set the number of susceptible CD4+T cells to
      the desired value. Simulation results confirm that the method is efficient even
      in the presence of parametric uncertainties. 

PMID- 24451397
TI  - Event-related brain potential study of semantic priming in unaffected first
      degree relatives of schizophrenia patients.
AB  - Schizophrenia is associated with abnormalities in using meaningful stimuli to
      activate or prime related concepts in semantic long-term memory. A
      neurophysiological index of this activation is the N400, an event-related brain
      potential (ERP) waveform elicited by meaningful stimuli, which is normally
      reduced (made less negative) by relatedness between the eliciting stimulus and
      preceding ones (N400 semantic priming). Schizophrenia patients exhibit N400
      semantic priming deficits, suggesting impairment in using meaningful context to
      activate related concepts. To address whether this abnormality is a trait-like
      marker of liability to schizophrenia or, alternatively, a biomarker of the
      illness itself, we tested for its presence in schizophrenia patients' unaffected
      biological relatives. We recorded ERPs from 12 unaffected first-degree relatives
      of schizophrenia patients, 12 schizophrenia patients, and 12 normal control
      participants (NCPs) who viewed prime words each followed at 300- or 750-ms
      stimulus-onset asynchrony (SOA) by an unrelated or related target word, or a
      nonword, in a lexical-decision task. As expected, across SOAs, NCPs exhibited
      smaller (less negative) N400 amplitudes for related versus unrelated targets. The
      same pattern held in relatives, whose N400 amplitudes for related and unrelated
      targets did not differ from NCPs'. In contrast, consistent with previous results,
      schizophrenia patients exhibited larger N400 amplitudes than NCPs (and relatives)
      for related targets, such that patients' N400 amplitudes for related and
      unrelated targets did not differ. N400 amplitudes for unrelated targets did not
      differ between the three groups. Thus, N400 semantic priming deficits in a visual
      word-pair paradigm may be an illness biomarker for schizophrenia. 

PMID- 24451398
TI  - A comparison of cardio-metabolic risk between the deficit and non-deficit
      subtypes of schizophrenia.

PMID- 24451399
TI  - Cervical spine fractures in elderly patients with hip fracture after low-level
      fall: an opportunity to refine prehospital spinal immobilization guidelines?
AB  - BACKGROUND: Conventional prehospital spine-assessment approaches based on low
      index of suspicion and mechanism of injury (MOI) result in the liberal
      application of spinal immobilization in trauma patients. A painful distracting
      injury (DI), such as a suspected hip fracture, historically has been a sufficient
      condition for immobilization, even in an elderly patient who suffers a simple
      fall from standing and exhibits no other risk factors for spinal injury. Because
      the elderly are at increased risk of hip fracture from low-level falls, and are
      also particularly susceptible to the discomfort and morbidity associated with
      immobilization, the prevalence of cervical spine (c-spine) fracture in this
      patient population was examined. METHODS: Hospital billing records were used to
      identify all cases of traumatic femur fracture in Minnesota (USA) in 2010-2011.
      Concurrent diagnosis and external cause codes were used to estimate the
      prevalence of c-spine fracture by age and MOI. RESULTS: Among 1,394 patients with
      femur fracture, 23 (1.7%) had a c-spine fracture. When the MOI was a fall from
      standing or sitting height and the patient age was >= 65, the prevalence dropped
      to 0.4% (2/565). The prevalence was similar when the definition of hip fracture
      additionally included pelvis fractures (0.5%; 11/2,441). Eight of the 11 patients
      with c-spine fracture had diagnosis codes indicative of criteria other than the
      DI that likely would have resulted in immobilization (eg, head injury and
      compromised mental status). CONCLUSIONS: C-spine fracture is extremely rare in
      elderly patients who sustain hip fracture as a result of a low-level fall, and
      appears to be accompanied frequently by other known predictors of spinal injury
      besides DI. More research is needed to determine whether conservative use of
      spinal immobilization may be warranted in elderly patients with hip fracture
      after low-level falls when the only criteria for immobilization is the
      distracting hip injury.

PMID- 24451403
TI  - Ritonavir-Mediated Induction of Apoptosis in Pancreatic Cancer Occurs via the
      RB/E2F-1 and AKT Pathways.
AB  - Recent observations suggest a lower incidence of malignancies in patients
      infected with HIV during treatment with Highly Active Anti-Retroviral Therapy
      (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir,
      a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal
      adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and
      PANC-1 were propagated under standard conditions and treated with serial
      dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent
      manner as well as activated the intrinsic apoptotic pathway in human pancreatic
      ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell
      cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced
      interaction of retinoblastoma protein (RB) with E2F-1 transcription factor;
      inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and
      subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with
      its consensus binding sites; inhibition of cell motility and invasiveness; and
      inhibition of the AKT pathway. Our results demonstrate a potential use of
      ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA
      approved for HIV, drug repositioning for PDAC would limit the costs and reduce
      risks. 

PMID- 24451404
TI  - Asymmetric Synthesis of Spirocyclic 2-Benzopyrans for Positron Emission
      Tomography of sigma1 Receptors in the Brain.
AB  - Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded chiral
      triols (R)-7 and (S)-7, which were cyclized with tosyl chloride in the presence
      of Bu2SnO to provide 2-benzopyrans (R)-4 and (S)-4 with high regioselectivity.
      The additional hydroxy moiety in the 4-position was exploited for the
      introduction of various substituents. Williamson ether synthesis and replacement
      of the Boc protective group with a benzyl moiety led to potent sigma1 ligands
      with high sigma1/sigma2-selectivity. With exception of the ethoxy derivative 16,
      the (R)-configured enantiomers represent eutomers with eudismic ratios of up to
      29 for the ester (R)-18. The methyl ether (R)-15 represents the most potent
      sigma1 ligand of this series of compounds, with a Ki value of 1.2 nM and an
      eudismic ratio of 7. Tosylate (R)-21 was used as precursor for the radiosynthesis
      of [18F]-(R)-20, which was available by nucleophilic substitution with K[18F]F
      K222 carbonate complex. The radiochemical yield of [18F]-(R)-20 was 18%-20%, the
      radiochemical purity greater than 97% and the specific radioactivity 175-300
      GBq/umol. Although radiometabolites were detected in plasma, urine and liver
      samples, radiometabolites were not found in brain samples. After 30 min, the
      uptake of the radiotracer in the brain was 3.4% of injected dose per gram of
      tissue and could be reduced by coadministration of the sigma1 antagonist
      haloperidol. [18F]-(R)-20 was able to label those regions of the brain, which
      were reported to have high density of sigma1 receptors. 

PMID- 24451405
TI  - Heart rate variability at limiting stationarity: evidence of neuro-cardiac
      control mechanisms operating at ultra-low frequencies.
AB  - This study considers the linkage of exogenously stimulated emotional stress with
      the neurogenic regulation of heart rate operating at very low frequencies. The
      objectives were three-fold: to consider the present evidence that such a linkage
      exists as a primary phenomenon; to compare the potential of a frequency-domain
      method and a time-domain method in revealing this phenomenon by characterizing
      heart rate variability (HRV) at frequencies of [0.0005...0.4] Hz and to design,
      implement and report a physiological experiment in which alternating periods of
      exposure to bland and high valence visual stimuli might reveal this phenomenon. A
      methodical challenge was to optimize the length of exposure to the stimulus such
      that subjects did not have time to habituate to stimuli, whilst acquiring
      sufficient data (heart beats) such that the ultra-low frequency (ULF) components
      of HRV could be described. With exposure times set to approximately 5 min, during
      which time the strength of the stimulus and the corresponding evoked response
      were considered stationary, the lowest HRV frequency component that could be
      characterized was 0.003 Hz. In trials with parametrically defined test data, the
      time-domain method based on the Ornstein-Uhlenbeck Gaussian process (OU-GP) was
      shown to be better than the frequency-domain method in describing the ULF
      components of the HRV. In an experimental cohort of 16 subjects, analysis using
      the OU-GP revealed evidence of cardiac regulatory mechanisms influenced by
      emotional valence operating in the bandwidth (ULF*) [0.002...0.01] Hz.

PMID- 24451406
TI  - Understanding health and disease with multidimensional single-cell methods.
AB  - Current efforts in the biomedical sciences and related interdisciplinary fields
      are focused on gaining a molecular understanding of health and disease, which is
      a problem of daunting complexity that spans many orders of magnitude in
      characteristic length scales, from small molecules that regulate cell function to
      cell ensembles that form tissues and organs working together as an organism. In
      order to uncover the molecular nature of the emergent properties of a cell, it is
      essential to measure multiple-cell components simultaneously in the same cell. In
      turn, cell heterogeneity requires multiple-cells to be measured in order to
      understand health and disease in the organism. This review summarizes current
      efforts towards a data-driven framework that leverages single-cell technologies
      to build robust signatures of healthy and diseased phenotypes. While some
      approaches focus on multicolor flow cytometry data and other methods are designed
      to analyze high-content image-based screens, we emphasize the so-called
      Supercell/SVM paradigm (recently developed by the authors of this review and
      collaborators) as a unified framework that captures mesoscopic-scale emergence to
      build reliable phenotypes. Beyond their specific contributions to basic and
      translational biomedical research, these efforts illustrate, from a larger
      perspective, the powerful synergy that might be achieved from bringing together
      methods and ideas from statistical physics, data mining, and mathematics to solve
      the most pressing problems currently facing the life sciences. 

PMID- 24451411
TI  - Impact of targeted therapy on outcome of chronic lymphocytic leukemia patients
      with relapsed del(17p13.1) karyotype at a single center.

PMID- 24451412
TI  - Residual neuromuscular blockade after anesthesia: a possible cause of
      postoperative aspiration-induced pneumonia.

PMID- 24451410
TI  - BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of
      response in myeloid malignancies.
AB  - Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid
      malignancies have remained elusive. RNA-interference drug modifier screens
      identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing
      targets. In further dissecting BCL-XL, BCL-2 and MCL-1 contribution to 5
      Azacytidine activity, siRNA silencing of BCL-XL and MCL-1, but not BCL-2,
      exhibited variable synergy with 5-Azacytidine in vitro. The BCL-XL, BCL-2 and BCL
      w inhibitor ABT-737 sensitized most cell lines more potently compared with the
      selective BCL-2 inhibitor ABT-199, which synergized with 5-Azacytidine mostly at
      higher doses. Ex vivo, ABT-737 enhanced 5-Azacytidine activity across primary
      AML, MDS and MPN specimens. Protein levels of BCL-XL, BCL-2 and MCL-1 in 577 AML
      patient samples showed overlapping expression across AML FAB subtypes and
      heterogeneous expression within subtypes, further supporting a concept of
      dual/multiple BCL-2 family member targeting consistent with RNAi and
      pharmacologic results. Consequently, silencing of MCL-1 and BCL-XL increased the
      activity of ABT-199. Functional interrogation of BCL-2 family proteins by BH3
      profiling performed on patient samples significantly discriminated clinical
      response versus resistance to 5-Azacytidine-based therapies. On the basis of
      these results, we propose a clinical trial of navitoclax (clinical-grade ABT-737)
      combined with 5-Azacytidine in myeloid malignancies, as well as to prospectively
      validate BH3 profiling in predicting 5-Azacytidine response. 

PMID- 24451413
TI  - Gas dialysis: a new perspective on extracorporeal ventilation.

PMID- 24451415
TI  - [Health promotion and quality of life in work in crisis].

PMID- 24451414
TI  - Regional blood acidification enhances extracorporeal carbon dioxide removal: a 48
      hour animal study.
AB  - BACKGROUND: Extracorporeal carbon dioxide removal has been proposed to achieve
      protective ventilation in patients at risk for ventilator-induced lung injury. In
      an acute study, the authors previously described an extracorporeal carbon dioxide
      removal technique enhanced by regional extracorporeal blood acidification. The
      current study evaluates efficacy and feasibility of such technology applied for
      48 h. METHODS: Ten pigs were connected to a low-flow veno-venous extracorporeal
      circuit (blood flow rate, 0.25 l/min) including a membrane lung. Blood
      acidification was achieved in eight pigs by continuous infusion of 2.5 mEq/min of
      lactic acid at the membrane lung inlet. The acid infusion was interrupted for 1 h
      at the 24 and 48 h. Two control pigs did not receive acidification. At baseline
      and every 8 h thereafter, the authors measured blood lactate, gases, chemistry,
      and the amount of carbon dioxide removed by the membrane lung (VCO2ML). The
      authors also measured erythrocyte metabolites and selected cytokines.
      Histological and metalloproteinases analyses were performed on selected organs.
      RESULTS: Blood acidification consistently increased VCO2ML by 62 to 78%, from 79
      +/- 13 to 128 +/- 22 ml/min at baseline, from 60 +/- 8 to 101 +/- 16 ml/min at 24
      h, and from 54 +/- 6 to 96 +/- 16 ml/min at 48 h. During regional acidification,
      arterial pH decreased slightly (average reduction, 0.04), whereas arterial
      lactate remained lower than 4 mEq/l. No sign of organ and erythrocyte damage was
      recorded. CONCLUSION: Infusion of lactic acid at the membrane lung inlet
      consistently increased VCO2ML providing a safe removal of carbon dioxide from
      only 250 ml/min extracorporeal blood flow in amounts equivalent to 50% production
      of an adult man.

PMID- 24451416
TI  - [Six-month outcome of 795 patients admitted to Annecy hospital emergency
      department for mild traumatic brain injury].
AB  - INTRODUCTION: Mild traumatic brain injuries (mTBI) are common, but their outcomes
      are not very well known. A prospective study was conducted in Annecy hospital,
      France (CHRA), to assess the incidence of disorders 6 months after the injury and
      to identify risk factors for persistent disorders. METHOD: All patients admitted
      to the emergency department after a mild brain injury between February 2006 and
      July 2007 were included. They were contacted by telephone 6 months later to
      detect (by questionnaire) the presence of persistent disorders. Patients
      reporting disorders were referred to the l ocal brain injury centre for a follow
      up check-up. RESULTS: Ninety three of the 795 patients contacted reported
      disorders: memory disorders (80%), sleep disorders (79%), headaches (65%),
      irritability (64%), speech disorders (64%) and concentration disorders (62%).
      Disorders at 6 months were independently associated with age, female gender,
      presence of headache at the initial examination and CT scan performed in the
      emergency department. DISCUSSION: The disorders reported in this study were
      consistent with the results of previous studies. As these disorders are usually
      nonspecific, a case-control study or an exposed-unexposed study would be
      necessary to determine whether or not these disorders are linked to mTBI.

PMID- 24451417
TI  - [Perceived needs and social participation of people with mild traumatic brain
      injury].
AB  - INTRODUCTION: Only limited data are available concerning the perception of
      quality of life and social participation of people with mild Traumatic Brain
      Injury (mTBI). The APIC personalized community integration support programme
      encourages people with TBI to achieve significant daily living or leisure
      activities. OBJECTIVES: To explore the social participation needs and
      expectations of people with mTBI. METHODS: 1) Qualitative multiple-case study; 2)
      Questionnaires based on Assessment of Activities of Daily Living Profile, Leisure
      Profile and Life Habits in the form of semi-structured interviews. RESULTS:
      Participants reported deterioration of their quality of life after the accident,
      especially affecting leisure activities and social role. They would like to have
      someone to help reduce their loneliness, reassure them and motivate them to start
      changing their lives. DISCUSSION: Unlike the main interventions provided by the
      social welfare and healthcare system and relatives, people with mTBI express the
      need for reassuring activities in public places to help them regain their social
      role and accept their new identity.

PMID- 24451418
TI  - [Psychiatric disorders observed in the Angers university hospital occupational
      psychopathology department].
AB  - INTRODUCTION: This epidemiological study was conducted on the medical records of
      168 employees consecutively evaluated by the occupational health psychiatrist
      between 2007 and 2009. METHODS: Psychiatric disorders were listed according to
      the WHO International Classification of Diseases. RESULTS: The diagnoses observed
      were anxiety disorder including post-traumatic stress disorder, major depressive
      episode, burn-out and work-related stress. Suicidal thoughts were systematically
      investigated and more often affected men and were associated with major
      depressive episodes, burn-out and post-traumatic stress disorder. DISCUSSION:
      This study opens several fields of reflection. The delayed management of
      suffering employees could be improved by better awareness and training of
      healthcare professionals in work-related mental health problems. Employees should
      be encouraged to more readily consult occupational health services. The creation
      of specific healthcare networks would avoid inappropriate treatment and delayed
      management that predispose to chronic disorders. A detailed analysis by policy
      makers on working conditions in post-modern societies is essential to prevent
      progression of mental suffering in the workplace.

PMID- 24451419
TI  - [Teacher educators and health education: from their concepts to their
      professional identity].
AB  - INTRODUCTION: The objective of this study was to determine why some teacher
      educators use health education actions as part of their teacher training.
      METHODS: We therefore studied the educators' discourse in order to identify
      factors affecting declared practices and adhesion to health education training.
      The study was conducted in two steps. Teacher educators were interviewed by
      telephone using a questionnaire and teacher training curricula were reviewed to
      assess current teacher training practices. A qualitative analysis was then
      conducted by structured telephone interviews of 16 teacher educators. RESULTS AND
      DISCUSSION: The teacher educators interviewed in this study presented a holistic
      approach to health and health education, focusing on the individual, which had a
      positive impact on implementation of health education training. All of the
      teacher educators interviewed had also adopted health education as part of their
      professional identity: they felt competent in health education, and considered it
      to be part of their job. However, most teacher trainers reported concepts and
      declared practices according to an application-based model, focussing on acquired
      knowledge, or a didactic model, focussing on implementation of projects. The
      holistic model, focussing on individual health, remained very marginal and was
      not part of teacher educators' perceptions of their role in the training future
      teachers.

PMID- 24451420
TI  - [Dental status and related factors in an occupational health service in Northern
      France].
AB  - BACKGROUND: Few data are available concerning the dental health of adults in
      France. This study was designed to describe dental status, oral health behaviour
      and factors associated with caries among workers followed by an occupational
      health service in Northern France. METHODS: A representative sample of workers
      was selected between May and July 2006. Data were collected by occupational
      health physicians using a questionnaire completed during a face-to-face interview
      and a dental examination. After descriptive analysis of the variables, two groups
      were defined according to the degree of caries as assessed by the Significant
      Caries Index. Factors associated with the degree of caries were investigated
      using logistic regression adjusted to age. RESULTS: 420 workers with a mean age
      of 34.6(+/-10.4) years were included. The mean DMFT (Decayed Missing Filled
      Teeth) score and the mean number of decayed teeth were 8.9 (+/- 6.5) and 1.3 (+/
      2.8), respectively. Three independent factors associated with high caries rates
      were identified: level of education less than Baccalaureate (ORa = 1.85; p <
      0.05), regular consumption of sweet snacks and/or sweet drinks (ORa = 2.01; p <
      0.05) and a last dental visit motivated by pain or a reason other than preventive
      care (ORa = 1.89; p < 0.05). CONCLUSION: This study showed a high need for care
      and oral health education in this population of workers. More oral health
      education programmes should be set up in the adult working population by
      occupational health services.

PMID- 24451421
TI  - [Transfer and sharing of public health knowledge: reflections on the components
      of a national information system in France].
AB  - It is becoming increasingly necessary, in France, to develop a more efficient
      public health policy and define research in terms of the perspective of its use
      for public decisions and clinical practice. One possible solution consists of
      knowledge transfer and sharing based on a continuous exchange and interaction
      process between scientists and potential users of research data - field workers
      and health policy decision-makers. Such a process would involve collaboration
      with users to help them apply the evidence produced by research as well as the
      mobilization of research scientists to develop research more adapted to needs.
      This article defines the goals of development of knowledge transfer in the French
      setting. The conceptual bases are defined and four strategic axes and their
      operational modalities are developed. This proposal also integrates all of the
      public authorities concerned: promote knowledge transfer; reinforce observation
      and diffusion of evidence and its usability; promote the development of more
      adapted public health research by facilitating research scientist /research data
      user relationships; assist the various parties in the exchange and sharing of
      knowledge. Apart from improving the efficiency of health policies, the
      development of knowledge transfer and sharing would also strengthen the
      credibility of certain intervention strategies, especially in the field of
      prevention, by designing evidence-based strategies. 

PMID- 24451422
TI  - [Validation of the IPC65 questionnaire: a tool to measure interdisciplinarity in
      clinical practice].
AB  - AIM: Interdisciplinary clinical practice has become an essential objective for
      the management of complex cases in a large number of health facilities in Quebec
      and elsewhere. However, this highly desirable practice cannot be implemented on
      demand and requires a carefully designed approach in combination with continuous
      feedback between the various partners involved in the management and functioning
      of an interdisciplinary team. The purpose of this research was to provide teams
      with a tool to help them identify their strengths and weaknesses in order to
      ensure continuous improvement. METHODS: Following a comprehensive review of the
      literature on microsystems ensuring interdisciplinarity in health, we identified
      a large number of elements considered to be important factors allowing effective
      interdisciplinarity. These factors were used to construct a questionnaire that
      was submitted to several stages of validation (qualitative and statistical)
      designed to enable health professionals to measure their degree of integration of
      the concepts allowing interdisciplinary clinical practice. RESULTS: This approach
      allowed validation of this questionnaire (Cronbach's alpha greater than 0.97).
      During the validation process, the number of questions of the questionnaire was
      reduced from 99 to 65. CONCLUSION: The various steps of validation of the
      questionnaire allowed the development of a relevant tool to promote continuous
      improvement of interdisciplinary clinical teams.

PMID- 24451423
TI  - [The impact of a general practitioner training program on the colorectal cancer
      screening participation rate].
AB  - AIM: Colorectal cancer mortality in France in 2011 was 13.8/100,000 men and
      8.2/100,000 women. As participation in mass screening remains insufficient,
      training was proposed to general practitioners in the Drome-Ardeche departments.
      The objective of this study was to assess the impact of this training after one
      year. METHODS: This study compared a group of trained volunteers with the other
      general practitioners in the two departments. The participation rate was measured
      in patients aged 50 to 74 years examined during the year following the training
      programme. The participation rate was then assessed on the total population of
      patients aged 50 to 74 seen by each practitioner, and the practitioner's degree
      of conviction (tests performed / test kits delivered) and the clarity of
      instructions (interpretable tests / tests performed) were assessed. RESULTS:
      Thirty-five general practitioners attended the training programme in Spring 2011.
      The number of tests performed in this group of trained GPs was 0.29 per target
      patient examined (vs 0.17 among the 604 practitioners who did not attend the
      training programme) with a significant difference (p < 0.0001). The number of
      tests performed on the total patient population aged 50 to 74 was 0.24 per
      patient (vs 0.14) with p < 0.001. The conviction index was 0.85 (vs 0.90) with p
      < 0.0008 and the clarity of instructions index was 0.94 (vs 0.93) (p not
      significant). CONCLUSION: The training programme had a limited impact on
      participation in colorectal cancer screening, but trained practitioners
      nevertheless distributed more test kits and more tests were performed.

PMID- 24451424
TI  - [Geographic distribution of supportive care for disabled young people].
AB  - AIM: To analyse the logic for the distribution of home care services for disabled
      children (SESSAD) in a context of under-equipment. METHODS: Questionnaire-based
      survey of 75 units (82% of the region's SESSAD units) concerning patient
      transport. Equipment and transport mapping. RESULTS: Support units for disabled
      children are often set up in the housing facilities that contributed to their
      creation. These sites are sometimes situated a long way from densely populated
      regions, thereby generating unnecessary travel times and expenses. Chronic under
      equipment makes these sites viable, as the various units are always full, despite
      their distance from the children for whom they provide support. Mapping
      illustrates the extensive recruitment zones overlapping several units managing
      similar patients. CONCLUSION: The major revision of accreditation of these units,
      planned for 2017, could lead to redefinition of geographical zones of
      accreditations. New unit opening procedures based on ARS calls for tenders may
      help to improve the geographical distribution of this supportive care.

PMID- 24451425
TI  - [Qualitative survey of the law of 5 July 2011 in the field of psychiatry].
AB  - The law of 5 July 2011 concerning the rights and protection of subjects in
      psychiatric care and the modalities of their management has been severely
      criticized and often rejected, both before and following its application in
      August 2011. This study was designed to describe and compare perceptions of this
      law by actors in the field, six months after application of the law. This
      qualitative study based on twenty-four interviewees from Isere and Savoie -
      including psychiatrists, judges, patients and families - shows that this law is
      not completely rejected in practice and that it provides a number of advantages:
      independent view of a judge, an initial observation period, rapid management for
      isolated patients presenting an immediately life-threatening risk, improvement of
      mandatory outpatient healthcare. However, the law of 5 July 2011 also raises a
      number of problems: hospital leave for more than twelve hours was strictly
      limited by the initial text; complex relationships between justice and
      psychiatry; insufficient funding; hearings are problematic as they are held
      early, in public, and sometimes outside of hospitals; excessive number of medical
      certificates; certain parts of the text are unclear. As is already the case for
      some of these issues (law of 23 September 2013), these problems should be
      resolved in order to ensure better law enforcement. 

PMID- 24451426
TI  - [Information and consent in dental care associated with biomedical research].
AB  - INTRODUCTION: Tooth extraction as a part of dental care provides an opportunity
      to obtain dental pulp stem cells that could constitute new therapeutic tools for
      craniofacial bone and teeth repair. However, the use of tooth as a biological
      sample of human origin must comply with legislation and ethical rules. METHODS: A
      systematic literature review was conducted using Medline, Reseau Rodin, EM
      Premium, Legifrance, and the Comite consultatif national d'ethique and Comite
      national odontologique d'ethique websites. RESULTS: A total of 32 articles were
      included. This review of the literature on ethical issues identified the
      principles allowing research to be conducted in the context of dental care, while
      respecting the patient's autonomy and dignity. CONCLUSION: The patient must
      receive clear and accurate information and must give his/her consent before using
      a tooth for research purposes. However, a number of problems remain unresolved.
      This study explains how patient information and consent in the context of
      biomedical research must remain an integral part of dental care based on an
      ethical relationship.

PMID- 24451427
TI  - [Impact of AQUASOU: a practice-based research program at the Rufisque Health
      Centre, Senegal].
AB  - INTRODUCTION: Due to the inadequacy of preventive strategies to reduce maternal
      and neonatal mortality, the current priority concerns emergency obstetric and
      neonatal care, as defined in the Improvement of the Quality and Access to
      Emergency Obstetric Healthcare programme (AQUASOU). The objective of this study
      was to assess the impact of the AQUASOU programme on improved availability and
      quality of healthcare in the Rufisque Health District in Senegal. METHODOLOGY: We
      conducted a qualitative and operational descriptive study evaluating the
      activities of the AQUASOU programme between May 2004 and December 2007:
      observation of Prenatal Consultations, supervision of emergency care,
      organization of "mirror meetings" and medical evacuation audits. The periods
      before and after setting-up of the programme were compared. RESULTS: These
      various activities had a real impact on indicators of accessibility and
      availability of healthcare. A consultation framework based on the principle of
      feedback control and a "practice review" approach allowed an improvement of the
      quality of care. The number of deliveries increased by 60%. The annual surgical
      activity was increased sevenfold and the number of evacuations to more
      specialised structures was decreased (0.4% versus 9.6%), while evacuations
      admitted to the local structure increased. The maternal mortality rate decreased
      from 656 to 435 per 100,000 live births. The stillbirth rate decreased from 51 to
      56 per thousand. The leading causes of death were bleeding complications
      (mortality of 3.7%) and paroxysmal complications of hypertension (mortality of
      2.7%).

PMID- 24451428
TI  - [Vitamin A supplementation in children under five during a one-week nutrition
      intensification program in Mali].
AB  - INTRODUCTION: The National Nutrition Week (NNW) is designed to achieve 80%
      coverage of vitamin A supplementation among children aged 6 to 59 months. The
      objectives of this study were to describe the modalities of implementation of the
      NNW in 2006 in Mali and to document parents' and health workers' opinions.
      METHODS: A qualitative and quantitative cross-sectional study was conducted in
      two phases in May and June 2006 in four health districts (Kita, Kolondieba, Dire
      and town VI of Bamako) selected at random. Individual interviews were conducted
      with Ministry of Health officials, partners and health workers. The focus groups
      were conducted with community leaders, carers / mothers of children. The coverage
      survey was conducted among 1,699 children aged 6 to 59 months. RESULTS: The
      channels most commonly used to increase public awareness were local radio (6/7
      cases), public criers (5/7) and community health workers or traditional leaders
      (2/7). The main sources of information for mothers were: health workers (39%),
      relatives / neighbours / friends (37%), local leaders (24%) and radio (25%).
      Vitamin A supplementation coverage was 90% (1,520/1,699) for children aged 6 to
      59 months. CONCLUSION: The NNW achieved its goal, but the National Department of
      Health should implement a door-to-door strategy and enhance communication in
      order to change behaviour.

PMID- 24451429
TI  - [The Burkinabe experience of the creation of a Community Advisory Committee to
      improve the support of HIV research projects].
AB  - INTRODUCTION: Community Advisory Committees (CAC) have become indicators of good
      community involvement in health research all over the world. CACs have been
      developed only recently in several Sub-Saharan African countries. Many countries
      wonder about how to create and ensure good functioning of a community advisory
      committee. The objective of this article is to describe the creation of two CACs
      in Burkina Faso. METHODS: This qualitative study comprised a literature review
      phase, a data collection phase conducted on a sample of 27 subjects (research
      scientists, representatives of AIDS associations or networks and the local
      technical and/or financial partners of these associations) and an implementation
      phase. Study participants were selected on a rational basis, the study complied
      with the ethical principles of research and data were transcribed and analysed
      manually. RESULTS: Scientists and/or community workers may initiate the creation
      of a CAC based on the following main elements: the profile of individuals and/or
      structures, the dynamism of CAC members, reinforcement of their skills and
      capacities. The CAC must be independent of research scientists and must be
      designed to be sustainable. DISCUSSION: The difficulties of sustainability and
      the poor perception of CACs remain major challenges. Continuing collaboration
      between CAC members and research scientists improves their knowledge in the field
      of research ethics, allowing the community to perceive CACs as supporters of
      research.

PMID- 24451430
TI  - [Sexual behavior and condom use by people living with HIV/AIDS in Gabon].
AB  - INTRODUCTION: The HIV/AIDS prevalence rate in Gabon in 2011 was 5% among subjects
      aged 15 to 49 years. The objective of this study was to describe sexuality and
      condom use among people living with HIV/AIDS (PLWH) by comparing those living in
      the capital with those living in two provinces of Gabon: Ogowe-Maritime (Port
      Gentil) and Ogowe-Moyen (Lambarene). METHODS: A 5-month, cumulative, cross
      sectional descriptive survey was conducted between May 2009 and September 2010
      among PLWH over the age of 18 years, attending Gabon treatment centres and
      treated with ARVs for at least six months. A simple random sampling method was
      used to construct this sample. This survey was conducted in seven different
      centres for PLWH. RESULTS: The survey was conducted among 422 PLWH treated with
      ARV for at least six months: 284 (67.3%) subjects in Libreville and 138 (32.7%)
      in the provinces. The F/M sex ratio was 0.71. In this sample, 68% of PLWH
      reported sexual intercourse at least once during the previous 6 months. 49.5% of
      PLWH declared that they always used a condom with their main partner (p = 0.0096)
      and 52.4% declared that they always used a condom with other partners (p <
      0.0001). 50.1% of PLWH also reported that their last sexual intercourse during
      the previous 6 months was with their main partner (p < 0.0001). CONCLUSION: The
      majority of patients on ARV therapy use condoms with their main partner and with
      occasional partners. Management and condom use are more effective in Libreville.

PMID- 24451431
TI  - [Seroprevalence of HIV infection in the context of a mobile counseling and
      voluntary testing strategy in rural areas of Cote d'Ivoire].
AB  - INTRODUCTION: In Cote d'Ivoire, HIV testing and counselling has been identified
      as a priority in the National 2006-2010 AIDS Strategic Plan, which is designed to
      evaluate the prevalence of HIV in rural areas measured by means of a mobile
      strategy. METHODS: We conducted a cross-sectional descriptive and analytical
      study from 1st April, 2007 to 31st March 2008 in six rural areas of Cote
      d'Ivoire: Dabou, San Pedro, Abengourou, Tanda, Daloa, and Soubre*. The study
      population consisted of subjects attending the mobile voluntary counselling and
      testing units. RESULTS: The mean prevalence of HIV infection in this study was
      5.30%. The mean prevalence rate in men was 5.26%, with a peak of 7.55% in the 30
      34 years age-group. The mean prevalence rate in women was 5.35%, with a peak of
      6.59% in the same age-group. Type HIV-1 was predominant (84.2% of the total). The
      most affected area was Dabou, with a rate three times higher (15.83%) than the
      average rate observed during the study. More educated people (university level)
      presented 3.5-fold (for men) or 6-fold (for women) higher infection rates than
      illiterate people. Although 100% of people who tested positive received a medical
      or community referral according to their specific needs, only 62.1% were first
      line referred for medical care. CONCLUSION: In the light of the results of this
      study, we believe that community mobilization must be redirected to the most
      severely affected populations to facilitate earlier diagnosis. Actions such as
      training and prevention based on communication to encourage changes of behaviour
      should therefore be priorities in the national counselling and testing programme.

PMID- 24451432
TI  - [Contribution of humanities and social sciences to the training of healthcare
      professionals in Africa: an experience in the context of the mother and child
      Priority Solidarity Fund].
AB  - The mother-and-child Priority Solidarity Fund is a programme supported by
      Cooperation Francaise in the fields of health, higher education and new
      technologies. It aims to achieve the Millennium Development Goals of reducing
      maternal and infantile mortality. This programme, focused on the training of
      trainers, is developing two innovative plans: digital resources and the
      integration of the humanities and social sciences. This second aspect is
      decisive: by aligning content, skills, and needs, it can place greater emphasis
      on preventive care and give a real meaning to the work of trainers. 

PMID- 24451434
TI  - A comparison of women with fibromyalgia syndrome to criterion fitness standards:
      a pilot study.
AB  - PURPOSE: To compare fitness of women with fibromyalgia syndrome (FMS) aged 50+
      with performance standards associated with functional independence in late life.
      METHODS: Data came from a longitudinal study tracking physical and cognitive
      function of 93 women with FMS and included the most recent symptoms, activity
      levels, and fitness assessments. RESULTS: Most women performed below criterion
      referenced fitness standards for all measures. Nearly 90% percent of those < 70
      years scored below the standard for lower body strength. Only ~20% of respondents
      < 70 years old met the criteria for aerobic endurance. A third of those aged over
      70 met the standard in agility and dynamic balance. Physical activity was
      positively associated with fitness performance, while pain and depression
      symptoms were negatively associated. DISCUSSION: High proportions of women with
      FMS do not meet fitness standards recommended for maintaining physical
      independence in late life, indicating a risk for disability. Regular fitness
      assessments and targeted exercise interventions are warranted.

PMID- 24451436
TI  - Olfactory impairment and subjective olfactory complaints independently predict
      conversion to dementia: a longitudinal, population-based study.
AB  - We examined whether conversion to dementia can be predicted by self-reported
      olfactory impairment and/or by an inability to identify odors. Common forms of
      dementia involve an impaired sense of smell, and poor olfactory performance
      predicts cognitive decline among the elderly. We followed a sample of 1529
      participants, who were within a normal range of overall cognitive function at
      baseline, over a 10-year period during which 159 were classified as having a
      dementia disorder. Dementia conversion was predicted from demographic variables,
      Mini-Mental State Examination score, and olfactory assessments. Self-reported
      olfactory impairment emerged as an independent predictor of dementia. After
      adjusting for effects of other predictors, individuals who rated their olfactory
      sensitivity as "worse than normal" were more likely to convert to dementia than
      those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95%
      confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor
      identification test also predicted conversion to dementia (OR per 1 point
      increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We
      suggest that assessing subjective olfactory complaints might supplement other
      assessments when evaluating the risk of conversion to dementia. Future studies
      should investigate which combination of olfactory assessments is most useful in
      predicting dementia conversion.

PMID- 24451437
TI  - Prior autoimmune disease and risk of monoclonal gammopathy of undetermined
      significance and multiple myeloma: a systematic review.
AB  - BACKGROUND: Several observational studies have investigated autoimmune disease
      and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS)
      and multiple myeloma. Findings have been largely inconsistent and hindered by the
      rarity and heterogeneity of the autoimmune disorders investigated. A systematic
      review of the literature was undertaken to evaluate the strength of the evidence
      linking prior autoimmune disease and risk of MGUS/multiple myeloma. METHODS: A
      broad search strategy using key terms for MGUS, multiple myeloma, and 50
      autoimmune diseases was used to search four electronic databases (PubMed,
      Medline, Embase, and Web of Science) from inception through November 2011.
      RESULTS: A total of 52 studies met the inclusion criteria, of which 32 were
      suitably comparable to perform a meta-analysis. "Any autoimmune disorder" was
      associated with an increased risk of both MGUS [n = 760 patients; pooled relative
      risk (RR) 1.42; 95% confidence interval (CI), 1.14-1.75] and multiple myeloma
      (n>2,530 patients; RR 1.13, 95% CI, 1.04-1.22). This risk was disease dependent
      with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95%
      CI, 1.21-2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25-1.80). CONCLUSIONS:
      Our findings, based on the largest number of autoimmune disorders and patients
      with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases
      and/or their treatment may be important in the etiology of MGUS/multiple myeloma.
      The strong associations observed for pernicious anemia suggest that anemia seen
      in plasma cell dyscrasias may be of autoimmune origin. IMPACT: Underlying
      mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment
      of autoimmune diseases may be important in the pathogenesis of MGUS/multiple
      myeloma.

PMID- 24451439
TI  - How do we know if we're innovating? Setting the strategy for innovation
      evaluation.

PMID- 24451438
TI  - Effects and barriers to deployment of telehealth wellness programs for chronic
      patients across 3 European countries.
AB  - BACKGROUND: Benefits of cardiopulmonary rehabilitation (CPR) in patients with
      chronic obstructive pulmonary disease (COPD) are well established, but long-term
      sustainability of training-induced effects and its translation into healthy
      lifestyles are unsolved issues. It is hypothesized that Integrated Care Services
      supported by Information and Communication Technologies (ICS-ICT) can overcome
      such limitations. In the current study, we explored 3 ICS-ICT deployment
      experiences conducted in Barcelona, Trondheim and Athens. METHODS: In the 3
      sites, a total of 154 patients completed an 8-week supervised CPR program.
      Thereafter, they were allocated either to an ICS-ICT group or to usual care (CPR
      + UC) during a follow-up period of at least 12 months with assessment of 6-min
      walking test (6MWT) as main outcome variable at all time points in the 3 sites.
      Because real deployment was prioritized, the interventions were adapted to site
      heterogeneities. RESULTS: In the ICS-ICT group from Barcelona (n = 77), the use
      of the personal health folder (PHF) was the cornerstone technological tool to
      empower COPD patients for self-management showing high applicability and user
      acceptance. Long-term sustainability of training-induced increase in exercise
      capacity was observed in ICS-ICT compared to the control group (p = 0.01).
      Likewise, ICS-ICT enhanced the activities domain of the SGRQ (p < 0.01) and daily
      physical activity (p = 0.03), not seen in controls. No effects of ICS-ICT were
      observed in Trondheim (n = 37), nor in Athens (n = 40), due to technological
      and/or organizational limitations. CONCLUSIONS: The study results suggest the
      potential of the ICS-ICT Barcelona's approach to enhance COPD management.
      Moreover, it allowed identification of the factors limiting transferability to
      the other sites. The research prompts the need for large multicenter trials
      specifically designed to assess effectiveness, efficiencies and transferability
      of this type of intervention.

PMID- 24451440
TI  - Developing dual role nursing staff-clinical instructor: a partnership model.
AB  - Supported by visionary leadership, a unique strategic-academic partnership model
      was established with grant support between the University of Maryland School of
      Nursing, Baltimore, and 13 Maryland hospitals to prepare hospital-based staff
      nurses as clinical instructors. Participating hospitals gained masters' degree
      prepared nurses able to lead the achievement of clinical and organizational
      goals. The schools of nursing gained additional access to clinical education
      resources to enable increased undergraduate enrollment. 

PMID- 24451441
TI  - The influence of emerging administrative scientists: an interview with Dr
      Christopher Friese.
AB  - This department highlights emerging nursing leaders who have demonstrated great
      work and much potential in advancing innovation and patient care leadership in
      practice, policy, research, education, and theory. This interview profiles
      Christopher Friese, PhD, RN, AOCN, FAAN, assistant professor, University of
      Michigan School of Nursing. 

PMID- 24451442
TI  - How Magnet(r) standards improve pediatric care.
AB  - This month's Magnet((r)) Perspectives profiles the journey of children's
      hospitals as they have embraced the concepts of the Magnet Recognition
      Program((r)).

PMID- 24451443
TI  - Designing tomorrow: an investment in our future leaders.

PMID- 24451444
TI  - Exploring early and future use of DNP prepared nurses within healthcare
      organizations.
AB  - A strategy to gather data on DNP utilization and impact was designed using
      Donabedian's conceptual model and was piloted by surveying chief nursing officers
      (CNOs) leading Michigan's public and teaching hospital systems. Few of the
      responding CNOs reported currently employing DNP-prepared nurses. The majority
      reported gaps in knowledge related to role expectations and projected outcomes
      from a DNP-prepared nurse. Nurse leaders should become familiar with the role
      competencies of the DNP in order to maximize the potential contribution of this
      new level of care provider to improving care quality and access. 

PMID- 24451445
TI  - Enhancing nursing practice by utilizing voice recognition for direct
      documentation.
AB  - Innovative strategies that preserve nursing time for direct patient care
      activities are needed. This study examined the utility, feasibility, and
      acceptability of voice recognition (VR) software to document nursing care and
      patient outcomes in an electronic health record in a simulated nursing care
      environment. A phase 1 trial included 5 iterative experiments with observations
      and nurse participant feedback to allow enhancements to the speech detection
      capabilities and refinement of the technology, software, and processes. Utility
      ratings improved over time; however, interference on nursing care remained a
      concern throughout. Nurse participants favored keyboard entry electronic health
      record, largely due to software and technical issues, but also relative to the
      culture shift the new technology brings to nursing practice. Successful adoption
      of VR technology by nursing will be dependent on receptiveness of the nurses and
      perceived benefits, timely access to education and training, and minimization of
      barriers to using the software. 

PMID- 24451446
TI  - Quality and financial impact of adding nurse practitioners to inpatient care
      teams.
AB  - OBJECTIVE: The purpose of this project was to examine the financial impact of
      adding nurse practitioners (NPs) to inpatient care teams at Vanderbilt University
      Hospital. BACKGROUND: National initiatives targeting quality, safe, and cost
      effective healthcare have created the optimal environment for NPs to showcase
      their abilities and contributions. Identifying outcomes that are directly
      affected by NPs and quantifying data in terms of dollars can be affirmation for
      the contribution of the NP practice. Value can be garnered in terms of revenue
      generation and cost-effectiveness of hiring NP providers; however, a considerable
      financial impact can be in cost avoidance and cost savings through NP-associated
      outcomes of care. METHODS: This was a retrospective, secondary analysis of return
      on investment after adding NPs to 5 teams. Software was used to abstract billing,
      acuity, and length of stay (LOS) data and NP-associated quality metrics. Billing
      data, LOS, and risk-adjusted LOS data for designated years before and after
      adding NPs were compared. RESULTS: Gross collections compared with expenses for 4
      NP-led teams for 2 year time periods were 62%, 36%, and 47%, and +32%. Average
      risk-adjusted LOS for the 5 time periods after adding NPs decreased and charges
      decreased, thus demonstrating less resource use. Most clinical outcomes improved
      beyond preproject baselines. CONCLUSION: This project demonstrated the value of
      adding NPs to inpatient care teams by means of generated revenue, reduction in
      LOS, and standardization of quality care.

PMID- 24451447
TI  - Evaluation of a TeamSTEPPS(c) initiative on staff attitudes toward teamwork.
AB  - Teamwork is a critical component of a patient safety culture, and highly
      functioning teams make fewer errors. The purpose of this study was to determine
      if a customized TeamSTEPPS((c)) training initiative would result in improved
      attitudes toward teamwork among nursing staff on an inpatient hospital unit.
      Analysis revealed significant increases in total scores as well as statistical
      significance on all 5 components of teamwork including team structure,
      leadership, situation monitoring, mutual support, and communication. Data support
      that TeamSTEPPS training can be useful to promote improved attitudes toward
      teamwork.

PMID- 24451448
TI  - Nursing contributions to chronic disease management in primary care.
AB  - BACKGROUND: As the prevalence of chronic diseases continues to increase, emphasis
      is being placed on the development of primary care strategies that enhance
      healthcare delivery. Innovations include interprofessional healthcare teams and
      chronic disease management strategies. OBJECTIVE: To determine the roles of
      nurses working in primary care settings in Ontario and the extent to which
      chronic disease management strategies have been implemented. METHODS: We
      conducted a cross-sectional survey of a random sample of primary care nurses,
      including registered practical nurses, registered nurses, and nurse
      practitioners, in Ontario between May and July 2011. RESULTS: Nurses in primary
      care reported engaging in chronic disease management activities but to different
      extents depending on their regulatory designation (licensure category). Chronic
      disease management strategy implementation was not uniform across primary care
      practices where the nurses worked. CONCLUSIONS: There is the potential to
      optimize and standardize the nursing role within primary care and improve the
      implementation of chronic disease management strategies.

PMID- 24451449
TI  - An empirical analysis of nurse retention: what keeps RNs in nursing?
AB  - OBJECTIVE: This study investigates the effects of stress, economic factors,
      altruism, and value congruence on intentions to leave jobs and the nursing
      profession. BACKGROUND: Retaining nurses will be critical for healthcare
      organizations as the demand for nurses increases. Regulation and cost pressures
      are changing the nursing work environment. METHODS: We surveyed 861 RNs in the
      southeastern United States. Structural equation modeling was used to analyze the
      survey. RESULTS: Results confirm the importance of stress and salaries and
      underscore the impact of both value congruence and altruism. Evidence shows a
      correlation between altruistic desires and intentions to leave the profession.
      CONCLUSIONS: Efforts to retain nurses should include matching nurse and
      organizational values. Initiatives need to be undertaken to increase professional
      autonomy and provide opportunities for the expression of altruism. Further
      research is indicated to investigate the unexpected result that highly altruistic
      nurses are leaving the profession.

PMID- 24451450
TI  - The impact of health information technology on staffing.
AB  - Hospitals nationwide must demonstrate meaningful use by 2015 or face fines. For
      over 20 years, researchers have attempted to assess the impact of electronic
      record keeping technologies on the quality, safety, and efficiency of care, but
      results are inconclusive and hospital managers have little evidence on which to
      base staffing decisions as we hurtle toward the era of the paperless hospital. 

PMID- 24451451
TI  - Resolving mixed algal species in hyperspectral images.
AB  - We investigated a lab-based hyperspectral imaging system's response from pure
      (single) and mixed (two) algal cultures containing known algae types and
      volumetric combinations to characterize the system's performance. The spectral
      response to volumetric changes in single and combinations of algal mixtures with
      known ratios were tested. Constrained linear spectral unmixing was applied to
      extract the algal content of the mixtures based on abundances that produced the
      lowest root mean square error. Percent prediction error was computed as the
      difference between actual percent volumetric content and abundances at minimum
      RMS error. Best prediction errors were computed as 0.4%, 0.4% and 6.3% for the
      mixed spectra from three independent experiments. The worst prediction errors
      were found as 5.6%, 5.4% and 13.4% for the same order of experiments.
      Additionally, Beer-Lambert's law was utilized to relate transmittance to
      different volumes of pure algal suspensions demonstrating linear logarithmic
      trends for optical property measurements. 

PMID- 24451452
TI  - Performance evaluation and comparative analysis of SubCarrier Modulation Wake-up
      Radio systems for energy-efficient wireless sensor networks.
AB  - Energy-efficient communication is one of the main concerns of wireless sensor
      networks nowadays. A commonly employed approach for achieving energy efficiency
      has been the use of duty-cycled operation of the radio, where the node's
      transceiver is turned off and on regularly, listening to the radio channel for
      possible incoming communication during its on-state. Nonetheless, such a paradigm
      performs poorly for scenarios of low or bursty traffic because of unnecessary
      activations of the radio transceiver. As an alternative technology, Wake-up Radio
      (WuR) systems present a promising energy-efficient network operation, where
      target devices are only activated in an on-demand fashion by means of a special
      radio signal and a WuR receiver. In this paper, we analyze a novel wake-up radio
      approach that integrates both data communication and wake-up functionalities into
      one platform, providing a reconfigurable radio operation. Through physical
      experiments, we characterize the delay, current consumption and overall
      operational range performance of this approach under different transmit power
      levels. We also present an actual single-hop WuR application scenario, as well as
      demonstrate the first true multi-hop capabilities of a WuR platform and simulate
      its performance in a multi-hop scenario. Finally, by thorough qualitative
      comparisons to the most relevant WuR proposals in the literature, we state that
      the proposed WuR system stands out as a strong candidate for any application
      requiring energy-efficient wireless sensor node communications. 

PMID- 24451453
TI  - Dimension reduction of multivariable optical emission spectrometer datasets for
      industrial plasma processes.
AB  - A new data dimension-reduction method, called Internal Information Redundancy
      Reduction (IIRR), is proposed for application to Optical Emission Spectroscopy
      (OES) datasets obtained from industrial plasma processes. For example in a
      semiconductor manufacturing environment, real-time spectral emission data is
      potentially very useful for inferring information about critical process
      parameters such as wafer etch rates, however, the relationship between the
      spectral sensor data gathered over the duration of an etching process step and
      the target process output parameters is complex. OES sensor data has high
      dimensionality (fine wavelength resolution is required in spectral emission
      measurements in order to capture data on all chemical species involved in plasma
      reactions) and full spectrum samples are taken at frequent time points, so that
      dynamic process changes can be captured. To maximise the utility of the gathered
      dataset, it is essential that information redundancy is minimised, but with the
      important requirement that the resulting reduced dataset remains in a form that
      is amenable to direct interpretation of the physical process. To meet this
      requirement and to achieve a high reduction in dimension with little information
      loss, the IIRR method proposed in this paper operates directly in the original
      variable space, identifying peak wavelength emissions and the correlative
      relationships between them. A new statistic, Mean Determination Ratio (MDR), is
      proposed to quantify the information loss after dimension reduction and the
      effectiveness of IIRR is demonstrated using an actual semiconductor manufacturing
      dataset. As an example of the application of IIRR in process monitoring/control,
      we also show how etch rates can be accurately predicted from IIRR dimension
      reduced spectral data. 

PMID- 24451454
TI  - RAZOR: a compression and classification solution for the Internet of Things.
AB  - The Internet of Things is expected to increase the amount of data produced and
      exchanged in the network, due to the huge number of smart objects that will
      interact with one another. The related information management and transmission
      costs are increasing and becoming an almost unbearable burden, due to the
      unprecedented number of data sources and the intrinsic vastness and variety of
      the datasets. In this paper, we propose RAZOR, a novel lightweight algorithm for
      data compression and classification, which is expected to alleviate both aspects
      by leveraging the advantages offered by data mining methods for optimizing
      communications and by enhancing information transmission to simplify data
      classification. In particular, RAZOR leverages the concept of motifs, recurrent
      features used for signal categorization, in order to compress data streams: in
      such a way, it is possible to achieve compression levels of up to an order of
      magnitude, while maintaining the signal distortion within acceptable bounds and
      allowing for simple lightweight distributed classification. In addition, RAZOR is
      designed to keep the computational complexity low, in order to allow its
      implementation in the most constrained devices. The paper provides results about
      the algorithm configuration and a performance comparison against state-of-the-art
      signal processing techniques. 

PMID- 24451455
TI  - A uniform energy consumption algorithm for wireless sensor and actuator networks
      based on dynamic polling point selection.
AB  - Recent research has indicated that using the mobility of the actuator in wireless
      sensor and actuator networks (WSANs) to achieve mobile data collection can
      greatly increase the sensor network lifetime. However, mobile data collection may
      result in unacceptable collection delays in the network if the path of the
      actuator is too long. Because real-time network applications require meeting data
      collection delay constraints, planning the path of the actuator is a very
      important issue to balance the prolongation of the network lifetime and the
      reduction of the data collection delay. In this paper, a multi-hop routing mobile
      data collection algorithm is proposed based on dynamic polling point selection
      with delay constraints to address this issue. The algorithm can actively update
      the selection of the actuator's polling points according to the sensor nodes'
      residual energies and their locations while also considering the collection delay
      constraint. It also dynamically constructs the multi-hop routing trees rooted by
      these polling points to balance the sensor node energy consumption and the
      extension of the network lifetime. The effectiveness of the algorithm is
      validated by simulation. 

PMID- 24451457
TI  - Quality factor effect on the wireless range of microstrip patch antenna strain
      sensors.
AB  - Recently introduced passive wireless strain sensors based on microstrip patch
      antennas have shown great potential for reliable health and usage monitoring in
      aerospace and civil industries. However, the wireless interrogation range of
      these sensors is limited to few centimeters, which restricts their practical
      application. This paper presents an investigation on the effect of circular
      microstrip patch antenna (CMPA) design on the quality factor and the maximum
      practical wireless reading range of the sensor. The results reveal that by using
      appropriate substrate materials the interrogation distance of the CMPA sensor can
      be increased four-fold, from the previously reported 5 to 20 cm, thus improving
      considerably the viability of this type of wireless sensors for strain
      measurement and damage detection. 

PMID- 24451456
TI  - On the capability of smartphones to perform as communication gateways in medical
      wireless personal area networks.
AB  - This paper evaluates and characterizes the technical performance of medical
      wireless personal area networks (WPANs) that are based on smartphones. For this
      purpose,a prototype of a health telemonitoring system is presented. The prototype
      incorporates a commercial Android smartphone, which acts as a relay point, or
      "gateway", between a set of wireless medical sensors and a data server.
      Additionally, the paper investigates if the conventional capabilities of current
      commercial smartphones can be affected by their use as gateways or "Holters" in
      health monitoring applications. Specifically, the profiling has focused on the
      CPU and power consumption of the mobile devices. These metrics have been measured
      under several test conditions modifying the smartphone model, the type of sensors
      connected to the WPAN, the employed Bluetooth profile (SPP (serial port profile)
      orHDP (health device profile)), the use of other peripherals, such as a GPS
      receiver, the impact of the use of the Wi-Fi interface or the employed method to
      encode and forward the data that are collected from the sensors.

PMID- 24451458
TI  - Design and mechanical evaluation of a capacitive sensor-based indexed platform
      for verification of portable coordinate measuring instruments.
AB  - During the last years, the use of Portable Coordinate Measuring Machines (PCMMs)
      in industry has increased considerably, mostly due to their flexibility for
      accomplishing in-line measuring tasks as well as their reduced costs and
      operational advantages as compared to traditional coordinate measuring machines
      (CMMs). However, their operation has a significant drawback derived from the
      techniques applied in the verification and optimization procedures of their
      kinematic parameters. These techniques are based on the capture of data with the
      measuring instrument from a calibrated gauge object, fixed successively in
      various positions so that most of the instrument measuring volume is covered,
      which results in time-consuming, tedious and expensive verification procedures.
      In this work the mechanical design of an indexed metrology platform (IMP) is
      presented. The aim of the IMP is to increase the final accuracy and to radically
      simplify the calibration, identification and verification of geometrical
      parameter procedures of PCMMs. The IMP allows us to fix the calibrated gauge
      object and move the measuring instrument in such a way that it is possible to
      cover most of the instrument working volume, reducing the time and operator
      fatigue to carry out these types of procedures. 

PMID- 24451460
TI  - Active design method for the static characteristics of a piezoelectric six-axis
      force/torque sensor.
AB  - To address the bottleneck issues of an elastic-style six-axis force/torque sensor
      (six-axis force sensor), this work proposes a no-elastic piezoelectric six-axis
      force sensor. The operating principle of the piezoelectric six-axis force sensor
      is analyzed, and a structural model is constructed. The static-active design
      theory of the piezoelectric six-axis force sensor is established, including a
      static analytical/mathematical model and numerical simulation model (finite
      element model). A piezoelectric six-axis force sensor experimental prototype is
      developed according to the analytical mathematical model and numerical simulation
      model, and selected static characteristic parameters (including sensitivity,
      isotropic degree and cross-coupling) are tested using this model with three
      approaches. The measured results are in agreement with the analytical results
      from the static-active design method. Therefore, this study has successfully
      established a foundation for further research into the piezoelectric multi-axis
      force sensor and an overall design approach based on static characteristics. 

PMID- 24451459
TI  - Technological solutions and main indices for the assessment of newborns'
      nutritive sucking: a review.
AB  - Nutritive Sucking (NS) is a highly organized process that is essential for
      infants' feeding during the first six months of their life. It requires the
      complex coordination of sucking, swallowing and breathing. The infant's inability
      to perform a safe and successful oral feeding can be an early detector of
      immaturity of the Central Nervous System (CNS). Even though the importance of
      early sucking measures has been confirmed over the years, the need for
      standardized instrumental assessment tools still exists. Clinicians would benefit
      from specifically designed devices to assess oral feeding ability in their
      routine clinical monitoring and decision-making process. This work is a review of
      the main instrumental solutions developed to assess an infant's NS behavior, with
      a detailed survey of the main quantities and indices measured and/or estimated to
      characterize sucking behavior skills and their development. The adopted sensing
      measuring systems will be described, and their main advantages and weaknesses
      will be discussed, taking into account their application to clinical practice, or
      to at-home monitoring as post-discharge assessment tools. Finally, the study will
      highlight the most suitable sensing solutions and give some prompts for further
      research. 

PMID- 24451461
TI  - Embedded ARM system for volcano monitoring in remote areas: application to the
      active volcano on Deception Island (Antarctica).
AB  - This paper describes the development of a multi-parameter system for monitoring
      volcanic activity. The system permits the remote access and the connection of
      several modules in a network. An embedded ARMTM processor has been used, allowing
      a great flexibility in hardware configuration. The use of a complete Linux
      solution (DebianTM) as Operating System permits a quick, easy application
      development to control sensors and communications. This provides all the
      capabilities required and great stability with relatively low energy consumption.
      The cost of the components and applications development is low since they are
      widely used in different fields. Sensors and commercial modules have been
      combined with other self-developed modules. The Modular Volcano Monitoring System
      (MVMS) described has been deployed on the active Deception Island (Antarctica)
      volcano, within the Spanish Antarctic Program, and has proved successful for
      monitoring the volcano, with proven reliability and efficient operation under
      extreme conditions. In another context, i.e., the recent volcanic activity on El
      Hierro Island (Canary Islands) in 2011, this technology has been used for the
      seismic equipment and GPS systems deployed, thus showing its efficiency in the
      monitoring of a volcanic crisis.

PMID- 24451462
TI  - Advanced technologies for the improvement of spray application techniques in
      spanish viticulture: an overview.
AB  - Spraying techniques have been undergoing continuous evolution in recent decades.
      This paper presents part of the research work carried out in Spain in the field
      of sensors for characterizing vineyard canopies and monitoring spray drift in
      order to improve vineyard spraying and make it more sustainable. Some methods and
      geostatistical procedures for mapping vineyard parameters are proposed, and the
      development of a variable rate sprayer is described. All these technologies are
      interesting in terms of adjusting the amount of pesticides applied to the target
      canopy. 

PMID- 24451463
TI  - Short-range six-axis interferometer controlled positioning for scanning probe
      microscopy.
AB  - We present a design of a nanometrology measuring setup which is a part of the
      national standard instrumentation for nanometrology operated by the Czech
      Metrology Institute (CMI) in Brno, Czech Republic. The system employs a full six
      axis interferometric position measurement of the sample holder consisting of six
      independent interferometers. Here we report on description of alignment issues
      and accurate adjustment of orthogonality of the measuring axes. Consequently,
      suppression of cosine errors and reduction of sensitivity to Abbe offset is
      achieved through full control in all six degrees of freedom. Due to the geometric
      configuration including a wide basis of the two units measuring in y-direction
      and the three measuring in z-direction the angle resolution of the whole setup is
      minimize to tens of nanoradians. Moreover, the servo-control of all six degrees
      of freedom allows to keep guidance errors below 100 nrad. This small range system
      is based on a commercial nanopositioning stage driven by piezoelectric
      transducers with the range (200 * 200 * 10) um. Thermally compensated miniature
      interferometric units with fiber-optic light delivery and integrated homodyne
      detection system were developed especially for this system and serve as sensors
      for othogonality alignment. 

PMID- 24451464
TI  - An ambulatory method of identifying anterior cruciate ligament reconstructed gait
      patterns.
AB  - The use of inertial sensors to characterize pathological gait has traditionally
      been based on the calculation of temporal and spatial gait variables from
      inertial sensor data. This approach has proved successful in the identification
      of gait deviations in populations where substantial differences from normal gait
      patterns exist; such as in Parkinsonian gait. However, it is not currently clear
      if this approach could identify more subtle gait deviations, such as those
      associated with musculoskeletal injury. This study investigates whether
      additional analysis of inertial sensor data, based on quantification of gyroscope
      features of interest, would provide further discriminant capability in this
      regard. The tested cohort consisted of a group of anterior cruciate ligament
      reconstructed (ACL-R) females and a group of non-injured female controls, each
      performed ten walking trials. Gait performance was measured simultaneously using
      inertial sensors and an optoelectronic marker based system. The ACL-R group
      displayed kinematic and kinetic deviations from the control group, but no
      temporal or spatial deviations. This study demonstrates that quantification of
      gyroscope features can successfully identify changes associated with ACL-R gait,
      which was not possible using spatial or temporal variables. This finding may also
      have a role in other clinical applications where small gait deviations exist. 

PMID- 24451465
TI  - Automatic rice crop height measurement using a field server and digital image
      processing.
AB  - Rice crop height is an important agronomic trait linked to plant type and yield
      potential. This research developed an automatic image processing technique to
      detect rice crop height based on images taken by a digital camera attached to a
      field server. The camera acquires rice paddy images daily at a consistent time of
      day. The images include the rice plants and a marker bar used to provide a height
      reference. The rice crop height can be indirectly measured from the images by
      measuring the height of the marker bar compared to the height of the initial
      marker bar. Four digital image processing steps are employed to automatically
      measure the rice crop height: band selection, filtering, thresholding, and height
      measurement. Band selection is used to remove redundant features. Filtering
      extracts significant features of the marker bar. The thresholding method is
      applied to separate objects and boundaries of the marker bar versus other areas.
      The marker bar is detected and compared with the initial marker bar to measure
      the rice crop height. Our experiment used a field server with a digital camera to
      continuously monitor a rice field located in Suphanburi Province, Thailand. The
      experimental results show that the proposed method measures rice crop height
      effectively, with no human intervention required. 

PMID- 24451466
TI  - Control framework for dexterous manipulation using dynamic visual servoing and
      tactile sensors' feedback.
AB  - Tactile sensors play an important role in robotics manipulation to perform
      dexterous and complex tasks. This paper presents a novel control framework to
      perform dexterous manipulation with multi-fingered robotic hands using feedback
      data from tactile and visual sensors. This control framework permits the
      definition of new visual controllers which allow the path tracking of the object
      motion taking into account both the dynamics model of the robot hand and the
      grasping force of the fingertips under a hybrid control scheme. In addition, the
      proposed general method employs optimal control to obtain the desired behaviour
      in the joint space of the fingers based on an indicated cost function which
      determines how the control effort is distributed over the joints of the robotic
      hand. Finally, authors show experimental verifications on a real robotic
      manipulation system for some of the controllers derived from the control
      framework. 

PMID- 24451467
TI  - Applicability of time-averaged holography for micro-electro-mechanical system
      performing non-linear oscillations.
AB  - Optical investigation of movable microsystem components using time-averaged
      holography is investigated in this paper. It is shown that even a harmonic
      excitation of a non-linear microsystem may result in an unpredictable chaotic
      motion. Analytical results between parameters of the chaotic oscillations and the
      formation of time-averaged fringes provide a deeper insight into computational
      and experimental interpretation of time-averaged MEMS holograms.

PMID- 24451468
TI  - Thermal balance analysis of a micro-thermoelectric gas sensor using catalytic
      combustion of hydrogen.
AB  - A thermoelectric gas sensor (TGS) with a combustion catalyst is a calorimetric
      sensor that changes the small heat of catalytic combustion into a signal voltage.
      We analyzed the thermal balance of a TGS to quantitatively estimate the sensor
      parameters. The voltage signal of a TGS was simulated, and the heat balance was
      calculated at two sections across the thermoelectric film of a TGS. The thermal
      resistances in the two sections were estimated from the thermal time constants of
      the experimental signal curves of the TGS. The catalytic combustion heat
      Q(catalyst) required for 1 mV of ?V(gas) was calculated to be 46.1 MUW. Using
      these parameters, we find from simulations for the device performance that the
      expected Q(catalyst) for 200 and 1,000 ppm H2 was 3.69 MUW and 11.7 MUW,
      respectively.

PMID- 24451469
TI  - Markov jump linear systems-based position estimation for lower limb exoskeletons.
AB  - In this paper, we deal with Markov Jump Linear Systems-based filtering applied to
      robotic rehabilitation. The angular positions of an impedance-controlled
      exoskeleton, designed to help stroke and spinal cord injured patients during
      walking rehabilitation, are estimated. Standard position estimate approaches
      adopt Kalman filters (KF) to improve the performance of inertial measurement
      units (IMUs) based on individual link configurations. Consequently, for a multi
      body system, like a lower limb exoskeleton, the inertial measurements of one link
      (e.g., the shank) are not taken into account in other link position estimation
      (e.g., the foot). In this paper, we propose a collective modeling of all inertial
      sensors attached to the exoskeleton, combining them in a Markovian estimation
      model in order to get the best information from each sensor. In order to
      demonstrate the effectiveness of our approach, simulation results regarding a set
      of human footsteps, with four IMUs and three encoders attached to the lower limb
      exoskeleton, are presented. A comparative study between the Markovian estimation
      system and the standard one is performed considering a wide range of parametric
      uncertainties. 

PMID- 24451470
TI  - A spatial division clustering method and low dimensional feature extraction
      technique based indoor positioning system.
AB  - Indoor positioning systems based on the fingerprint method are widely used due to
      the large number of existing devices with a wide range of coverage. However,
      extensive positioning regions with a massive fingerprint database may cause high
      computational complexity and error margins, therefore clustering methods are
      widely applied as a solution. However, traditional clustering methods in
      positioning systems can only measure the similarity of the Received Signal
      Strength without being concerned with the continuity of physical coordinates.
      Besides, outage of access points could result in asymmetric matching problems
      which severely affect the fine positioning procedure. To solve these issues, in
      this paper we propose a positioning system based on the Spatial Division
      Clustering (SDC) method for clustering the fingerprint dataset subject to
      physical distance constraints. With the Genetic Algorithm and Support Vector
      Machine techniques, SDC can achieve higher coarse positioning accuracy than
      traditional clustering algorithms. In terms of fine localization, based on the
      Kernel Principal Component Analysis method, the proposed positioning system
      outperforms its counterparts based on other feature extraction methods in low
      dimensionality. Apart from balancing online matching computational burden, the
      new positioning system exhibits advantageous performance on radio map clustering,
      and also shows better robustness and adaptability in the asymmetric matching
      problem aspect. 

PMID- 24451471
TI  - A secure trust establishment scheme for wireless sensor networks.
AB  - Trust establishment is an important tool to improve cooperation and enhance
      security in wireless sensor networks. The core of trust establishment is trust
      estimation. If a trust estimation method is not robust against attack and
      misbehavior, the trust values produced will be meaningless, and system
      performance will be degraded. We present a novel trust estimation method that is
      robust against on-off attacks and persistent malicious behavior. Moreover, in
      order to aggregate recommendations securely, we propose using a modified one-step
      M-estimator scheme. The novelty of the proposed scheme arises from combining past
      misbehavior with current status in a comprehensive way. Specifically, we
      introduce an aggregated misbehavior component in trust estimation, which assists
      in detecting an on-off attack and persistent malicious behavior. In order to
      determine the current status of the node, we employ previous trust values and
      current measured misbehavior components. These components are combined to obtain
      a robust trust value. Theoretical analyses and evaluation results show that our
      scheme performs better than other trust schemes in terms of detecting an on-off
      attack and persistent misbehavior. 

PMID- 24451473
TI  - Prevalence of pathogenic Yersinia enterocolitica in slaughter-aged pigs during a
      one-year survey, 2010-2011, France.
AB  - The prevalence of pathogenic Yersinia enterocolitica in French slaughter-aged
      pigs was estimated by sampling 3120 pigs from 96 batches in 16 slaughterhouses
      from January 2010 to February 2011. Respectively, 36 batches (20 pigs/batch) and
      60 batches (40 pigs/batch) were considered during the cold period and the warm
      period. Tonsils were swabbed before the chilling step. Pathogenic Y.
      enterocolitica was detected after enrichment in ITC and streaking on CIN and YeCM
      media. Typical isolates were confirmed as Y. enterocolitica and biotyped by
      biochemical tests as described in the ISO 10273:2003 method. Of the tested pigs,
      13.7% (CI95% [10.1-17.3]) were found positive for pathogenic Y. enterocolitica
      and 74.3% (CI95% [64.8-83.8]) of the pig batches contained at least one positive
      pig. The percentage of positive pigs per batch was generally low; 60.3% of
      positive batches contained fewer than 5 positive pigs. The prevalence of the
      pathogen at the batch level remained unchanged throughout this one-year study,
      but the prevalence in pigs was significantly higher during the warm period than
      during the cold period. Biotype 4 was the most prevalent biotype among the 827
      isolated strains (91.9% of the isolates), followed by biotype 3 (7.25% of the
      isolates). Six isolates were of biotype 5 and one of biotype 2. Biotype 4 was
      found in all the 16 participating slaughterhouses, biotype 3 in ten
      slaughterhouses and biotype 5 in four. This study provides valuable recent
      figures for the prevalence of pathogenic Y. enterocolitica in French pigs. It
      also highlights the seasonal aspect of the carriage of this pathogen by pigs, a
      pattern which differs from those in other countries. 

PMID- 24451474
TI  - The magnetic resonance imaging-based approach for identification of high-risk
      patients with upper rectal cancer.
AB  - OBJECTIVE: To assess the efficacy of preoperative magnetic resonance imaging
      (MRI) in identifying upper rectal cancer patients who are at high risk for local
      recurrence. METHODS: 110 upper rectal cancer patients with locally advanced (pT3
      4N0 or pTanyN+) tumors treated with tumor-specific mesorectal excision and no
      adjuvant radiotherapy were identified from an institutional database at a large
      academic medical center in Korea. Information on the extent of mesorectal
      invasion, sacral-side involvement was collected from preoperative MRI. RESULTS:
      At a median follow-up of 47 months, 5 patients (4.5%) experienced local
      recurrence (LR). LR rates for patients with intermediate risk (T1-2/N1, T3N0),
      moderately high risk (T1-2/N2, T3N1, T4N0), and high risk (T3N2, T4/N1-2) were
      3%, 4.8%, and 8.7%, respectively. Patients who did not have sacral-side
      involvement or mesorectal invasion of 5 mm or less did not experience LR. The
      patients with sacral-side involvement and intermediate risk, moderately high
      risk, and high risk had an LR rate of 4.2%, 5.6%, and 10%, respectively, or
      11.1%, 33.3%, and 18.2%, respectively, when combined with those with mesorectal
      invasion of greater than 5 mm. Multivariate analyses demonstrated the presence of
      both sacral-side location and mesorectal invasion of greater than 5 mm was
      significantly associated with adverse disease-free and overall survival (P <
      0.05). CONCLUSIONS: Patients with mesorectal invasion of greater than 5 mm and
      sacral-side involvement identified on MRI were at an increased risk of local
      recurrence. The detection of these features on MRI provides prognostic
      information that is not available in conventional risk classification systems.
      Improved identification of a high-risk subset of upper rectal cancer patients may
      guide indications for preoperative chemoradiotherapy in this subset.

PMID- 24451475
TI  - The influence of carbon monoxide bolus on the measurement of total haemoglobin
      mass using the optimized CO-rebreathing method.
AB  - The optimized carbon monoxide (CO) rebreathing method (oCOR-method) is routinely
      used to measure total haemoglobin mass (tHbmass). The tHbmass measure is subject
      to a test-retest typical error of ~2%, mostly from the precision of
      carboxyhaemoglobin (HbCO) measurement. We hypothesized that tHbmass would be
      robust to differences in the bolus of CO administered during the oCOR-method.
      Twelve participants (ten males and two females; age 27 +/- 6 yr, height 177 +/-
      11 cm and mass 73.9 +/- 12.1 kg) completed the oCOR-method on four occasions.
      Different bolus of CO were administered (LOW: 0.6 ml kg(-1); MED1: 1.0 ml kg(-1)
      and HIGH: 1.4 ml kg(-1)); to determine the reliability of MED1, a second trial
      was conducted (MED2). tHbmass was found to be significantly less from the HIGH CO
      bolus (776 +/- 148 g) when compared to the LOW CO (791 +/- 149 g) or MED1 CO (788
      +/- 149 g) trials. MED2 CO was 785 +/- 150 g. The measurement of tHbmass is
      repeatable to within 0.8%, but a small and notable difference was seen when using
      a HIGH CO bolus (1.4 to 1.9% less), potentially due to differences in CO uptake
      kinetics. Previously, an improved precision of the oCOR-method was thought to
      require a higher bolus of CO (i.e. larger Delta%HbCO), as commercial hemoximeters
      only estimate %HbCO levels to a single decimal place (usually +/- 0.1%). With the
      new hemoximeter used in this study, a bolus of 1.0 ml kg(-1) allows adequate
      precision with acceptable safety.

PMID- 24451476
TI  - Attitudes toward physical activity and exercise: comparison of memory clinic
      patients and their caregivers and prediction of activity levels.
AB  - Regular physical activity and exercise (PA&E) reduces cognitive aging, may delay
      dementia onset, and for persons with dementia, may slow progression and improve
      quality of life. Memory clinic patients and caregivers described their PA&E and
      completed the Older Persons' Attitudes Toward Physical Activity and Exercise
      Questionnaire (OPAPAEQ). Caregivers and patients differed in their PA&E
      attitudes: patients were less likely to believe in the importance of PA&E for
      health promotion. PA&E attitudes were explored as predictors of self-reported
      exercise habits. Belief in the importance of high intensity exercise for health
      maintenance was the only variable that significantly predicted engagement in
      regular PA&E. Moreover, caregivers' attitudes toward high intensity exercise
      predicted memory patients' participation in PA&E. These findings may aid in
      development of exercise interventions for people with memory problems, and
      suggest that modification of specific attitudes toward exercise is an important
      component to ensure maximum participation and engagement in PA&E. 

PMID- 24451477
TI  - Sedimentation dynamics and equilibrium profiles in multicomponent mixtures of
      colloidal particles.
AB  - In this paper we give a general theoretical framework that describes the
      sedimentation of multicomponent mixtures of particles with sizes ranging from
      molecules to macroscopic bodies. Both equilibrium sedimentation profiles and the
      dynamic process of settling, or its converse, creaming, are modeled. Equilibrium
      profiles are found to be in perfect agreement with experiments. Our model
      reconciles two apparently contradicting points of view about buoyancy, thereby
      resolving a long-lived paradox about the correct choice of the buoyant density.
      On the one hand, the buoyancy force follows necessarily from the suspension
      density, as it relates to the hydrostatic pressure gradient. On the other hand,
      sedimentation profiles of colloidal suspensions can be calculated directly using
      the fluid density as apparent buoyant density in colloidal systems in
      sedimentation-diffusion equilibrium (SDE) as a result of balancing gravitational
      and thermodynamic forces. Surprisingly, this balance also holds in multicomponent
      mixtures. This analysis resolves the ongoing debate of the correct choice of
      buoyant density (fluid or suspension): both approaches can be used in their own
      domain. We present calculations of equilibrium sedimentation profiles and dynamic
      sedimentation that show the consequences of these insights. In bidisperse
      mixtures of colloids, particles with a lower mass density than the homogeneous
      suspension will first cream and then settle, whereas particles with a suspension
      matched mass density form transient, bimodal particle distributions during
      sedimentation, which disappear when equilibrium is reached. In all these cases,
      the centers of the distributions of the particles with the lowest mass density of
      the two, regardless of their actual mass, will be located in equilibrium above
      the so-called isopycnic point, a natural consequence of their hard-sphere
      interactions. We include these interactions using the Boublik-Mansoori-Carnahan
      Starling-Leland (BMCSL) equation of state. Finally, we demonstrate that our model
      is not limited to hard spheres, by extending it to charged spherical particles,
      and to dumbbells, trimers and short chains of connected beads. 

PMID- 24451479
TI  - Multiple isotope analyses of the pike tapeworm Triaenophorus nodulosus reveal
      peculiarities in consumer-diet discrimination patterns.
AB  - Previous studies of dietary isotope discrimination have led to the general
      expectation that a consumer will exhibit enriched stable isotope levels relative
      to its diet. Parasite-host systems are specific consumer-diet pairs in which the
      consumer (parasite) feeds exclusively on one dietary source: host tissue.
      However, the small numbers of studies previously carried out on isotopic
      discrimination in parasite-host (DeltaXP-HT) systems have yielded controversial
      results, showing some parasites to be isotopically depleted relative to their
      food source, while others are enriched or in equilibrium with their hosts.
      Although the mechanism for these deviations from expectations remains to be
      understood, possible influences of specific feeding niche or selection for only a
      few nutritional components by the parasite are discussed. DeltaXP-HT for multiple
      isotopes (delta13C, delta15N, delta34S) were measured in the pike tapeworm
      Triaenophorus nodulosus and two of its life-cycle fish hosts, perch Perca
      fluviatilis and pike Esox lucius, within which T. nodulosus occupies different
      feeding locations. Variability in the value of DeltaXP-HT calculated for the
      parasite and its different hosts indicates an influence of feeding location on
      isotopic discrimination. In perch liver DeltaXP-HT was relatively more negative
      for all three stable isotopes. In pike gut DeltaXP-HT was more positive for
      delta13C, as expected in conventional consumer-diet systems. For parasites
      feeding on pike gut, however, the delta15N and delta34S isotope values were
      comparable with those of the host. We discuss potential causes of these
      deviations from expectations, including the effect of specific parasite feeding
      niches, and conclude that DeltaXP-HT should be critically evaluated for trophic
      interactions between parasite and host before general patterns are assumed. 

PMID- 24451478
TI  - Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival
      mechanism.
AB  - BACKGROUND: Unlike glycolytic enzymes that directly catabolize glucose to
      pyruvate, the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases
      (PFKFBs) control the conversion of fructose-6-phosphate to and from fructose-2,6
      bisphosphate, a key regulator of the glycolytic enzyme phosphofructokinase-1 (PFK
      1). One family member, PFKFB3, has been shown to be highly expressed and
      activated in human cancer cells, and derivatives of a PFKFB3 inhibitor, 3-(3
      pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), are currently being developed in
      clinical trials. However, the effectiveness of drugs such as 3PO that target
      energetic pathways is limited by survival pathways that can be activated by
      reduced ATP and nutrient uptake. One such pathway is the process of cellular self
      catabolism termed autophagy. We hypothesized that the functional glucose
      starvation induced by inhibition of PFKFB3 in tumor cells would induce autophagy
      as a pro-survival mechanism and that inhibitors of autophagy could increase the
      anti-tumor effects of PFKFB3 inhibitors. RESULTS: We found that selective
      inhibition of PFKFB3 with either siRNA transfection or 3PO in HCT-116 colon
      adenocarcinoma cells caused a marked decrease in glucose uptake simultaneously
      with an increase in autophagy based on LC3-II and p62 protein expression,
      acridine orange fluorescence of acidic vacuoles and electron microscopic
      detection of autophagosomes. The induction of autophagy caused by PFKFB3
      inhibition required an increase in reactive oxygen species since N-acetyl
      cysteine blocked both the conversion of LC3-I to LC3-II and the increase in
      acridine orange fluorescence in acidic vesicles after exposure of HCT-116 cells
      to 3PO. We speculated that the induction of autophagy might protect cells from
      the pro-apoptotic effects of 3PO and found that agents that disrupt autophagy,
      including chloroquine, increased 3PO-induced apoptosis as measured by double
      staining with Annexin V and propidium iodide in both HCT-116 cells and Lewis lung
      carcinoma (LLC) cells. Chloroquine also increased the anti-growth effect of 3PO
      against LLCs in vivo and resulted in an increase in apoptotic cells within the
      tumors. CONCLUSIONS: We conclude that PFKFB3 inhibitors suppress glucose uptake,
      which in turn causes an increase in autophagy. The addition of selective
      inhibitors of autophagy to 3PO and its more potent derivatives may prove useful
      as rational combinations for the treatment of cancer.

PMID- 24451480
TI  - The need for development of protocol for managing refractory cerebral vasospasm.

PMID- 24451481
TI  - Protocol for vasospasm.

PMID- 24451483
TI  - In vivo activity of modafinil on dopamine transporter measured with positron
      emission tomography and [18F]FE-PE2I.
AB  - Modafinil, a wake-promoting drug used to treat narcolepsy, is a dopamine
      transporter inhibitor and is said to have very low abuse liability; this,
      however, is still up for debate. We conducted a dopamine transporter (DAT)
      occupancy study with modafinil (200 or 300 mg) in ten healthy volunteers using
      positron emission tomography (PET) with [18F]FE-PE2I, a new PET radioligand with
      high affinity and selectivity for the dopamine transporter, to characterize its
      relation to abuse liability. Mean striatal DAT occupancies were 51.4% at 200 mg
      and 56.9% at 300 mg. There was a significant correlation between occupancy and
      plasma concentration, indicating dose dependency of DAT inhibition by modafinil
      in the striatum, and especially in the nucleus accumbens. This study showed that
      DAT occupancy by modafinil was close to that of methylphenidate, indicating that
      modafinil may be near the same level as methylphenidate in relation to abuse
      liability in terms of dopaminergic transmission.

PMID- 24451491
TI  - Photocontrol of the mitotic kinesin Eg5 using a novel S-trityl-L-cysteine
      analogue as a photochromic inhibitor.
AB  - Because the mitotic kinesin Eg5 is essential for the formation of bipolar
      spindles during eukaryotic cell division, it has been considered as a potential
      target for cancer treatment. A number of specific and potent inhibitors of Eg5
      are known. S-trityl-L-cysteine is one of the inhibitors of Eg5 whose molecular
      mechanism of inhibition was well studied. The trityl group of S-trityl-L-cysteine
      was shown to be a key moiety required for potent inhibition. In this study, we
      synthesized a novel photochromic S-trityl-L-cysteine analogue, 4-(N-(2-(N
      acetylcysteine-S-yl) acetyl) amino)-4'- (N-(2-(N
      (triphenylmethyl)amino)acetyl)amino)azobenzene (ACTAB), composed of a trityl
      group, azobenzene and N-acetyl-L-cysteine, which exhibits cis-trans
      photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited
      cis-trans photoisomerization upon alternating irradiation at two different
      wavelengths in the visible range, 400 and 480 nm. ACTAB induced reversible
      changes in the inhibitory activity of ATPase and motor activities correlating
      with the cis-trans photoisomerization. Compared with cis-ACTAB, trans-ACTAB
      reduced ATPase activity and microtubule gliding velocity more significantly.
      These results suggest that ACTAB could be used as photochromic inhibitor of Eg5
      to achieve photocontrol of living cells.

PMID- 24451492
TI  - Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances
      cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish
      embryo.
AB  - Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are second
      generation lysophospholipid mediators that exert multiple biological functions
      through their own cognate receptors. They are both present in the blood stream,
      activate receptors with similar structures (endothelial differentiation gene
      receptors), have similar roles in the vasculature and are vasoactive. However, it
      is unclear whether these lysophospholipid mediators cross-talk downstream of each
      receptor. Here, we provide in vivo evidence that LPA signaling counteracted S1P
      signaling. When autotaxin (Atx), an LPA-producing enzyme, was overexpressed in
      zebrafish embryos by injecting atx mRNA, the embryos showed cardia bifida, a
      phenotype induced by down-regulation of S1P signaling. A similar cardiac
      phenotype was not induced when catalytically inactive Atx was introduced. The
      cardiac phenotype was synergistically enhanced when antisense morpholino
      oligonucleotides (MO) against S1P receptor (s1pr2/mil) or S1P transporter (spns2)
      was introduced together with atx mRNA. The Atx-induced cardia bifida was
      prominently suppressed when embryos were treated with an lpar1 receptor
      antagonist, Ki16425, or with MO against lpar1. These results provide the first in
      vivo evidence of cross-talk between LPA and S1P signaling. 

PMID- 24451493
TI  - Calcium-dependent structural changes in human reticulocalbin-1.
AB  - Human reticulocalbin-1 (hRCN1) has six EF-hand motifs and binds Ca(2+). hRCN1 is
      a member of the CREC family localized in the secretory pathway, and its cellular
      function remains unclear. In this study, we established a new bacterial
      expression and purification procedure for hRCN1. We observed that hRCN1 binds
      Ca(2+) in a cooperative manner and the Ca(2+) binding caused an increase in the
      alpha-helix content of hRCN1. On the other hand, hRCN1 did not change the
      structure with Mg(2+) loading. hRCN1 is a monomeric protein, and its overall
      structure became more compact upon Ca(2+) binding, as revealed by gel-filtration
      column chromatography and small-angle X-ray scattering. This is the first report
      of conformational changes in the CREC family upon Ca(2+) binding. Our data
      suggest that CREC family member interactions with target proteins are regulated
      in the secretory pathway by conformational changes upon Ca(2+) binding. 

PMID- 24451494
TI  - [Epidemiology of tinea capitis in outpatients at the Children's Hospital in Rabat
      (Morocco)].
AB  - OBJECTIVE: The aims of this report on results of a retrospective study were to
      identify the incidence of this pathology among outpatients at the Children's
      Hospital in Rabat, Morocco, the species involved, their respective prevalence,
      and the influence of the age and sex of the patient. PATIENTS AND METHODS:
      Between 1993 and 2007, a mycological examination was performed on 2962 patients
      in the dermatology service of Ibn Sina University Health Center in Rabat. Mean
      patient age was 35 (ages ranged from three months to 70 years). RESULTS: Direct
      microscopic examination was made of all the patients' hair, followed by culture
      on Sabouraud medium leading to the identification of scalp ringworm in 1299
      patients. The age group most affected was children under ten years of age (50% of
      the cases), mostly boys (M: F sex-ratio 1:14). The majority of cases of ringworm
      in our study were caused by Trichophyton mentagrophytes with 992 cases (76.4%),
      followed by Microsporum canis with 174 cases (13.4%). Inflammatory ringworm was
      identified in 32 patients (2.5%) and 30 cases of honeycomb ringworm (tinea
      favosa) (2.3%). Trichophyton violaceum was more frequent among girls and M. canis
      was more frequent among boys. Analysis of the incidence of the different species
      over the years revealed a clear decrease in case of tinea favosa, a decreasing
      trend for T. violaceum and a significant recrudescence of M. canis. CONCLUSION:
      T. violaceum continues to be the most common species of scalp ringworm in
      Morocco, despite a significant increase in M. canis. Tinea favosa has been
      practically eradicated.

PMID- 24451495
TI  - [Current aspects of neuromeningeal cryptococcosis in adults infected with HIV in
      the internal medicine service of the University Hospital of Treichville Abidjan
      (Cote d'Ivoire)].
AB  - OBJECTIVES: To determine the prevalence of neuromeningeal cryptococcosis (NMC)
      and reporting sociodemographic, clinical, paraclinical aspects and outcome of
      patients. METHODS: It was a retrospective study concerning 22 HIV positive
      patients hospitalized between 2006 to and 2009 in the internal medicine service
      of University Hospital of Treichville for NMC. RESULTS: The prevalence of NMC in
      patients infected with HIV was 0.6%. The mean age was 35+/-4.5 years old. The sex
      ratio was 0.5. The average time evolution of the symptomatology was 10+/-2.1
      days. The installation of the disease was progressive (86.4%). The main signs
      were fever (100%) and headache (95.4%). The cerebrospinal fluid was inflammatory
      aspect (95.4%) with low glucose (91%), hyper lymphocytosis(100%). There were
      Cryptococcus neoformans in direct exam by China ink (72.7%) and culture on
      Sabouraud (100%). Treatment was injectable amphoterin B in monotherapy (54.5%)
      followed by fluconazole per os (45.5%). The mortality was 54.5%. CONCLUSION: This
      study shows a reduction of NMC prevalence in our service in relation with
      tritherapy.

PMID- 24451496
TI  - Study on fungal flora of tap water as a potential reservoir of fungi in hospitals
      in Sari city, Iran.
AB  - OBJECTIVE: The aim of the present investigation was to evaluate the fungal flora
      of tap water from university hospitals of Sari city, Iran. MATERIALS AND METHODS:
      During a 1-year period, 240 water samples were collected from four university
      hospitals. All water samples were collected in sterile polystyrene bottles. A
      volume of 100ml of the samples passed through sterile 0.45-micrometer filters.
      The filters were placed directly on malt extract agar and incubated at 27 degrees
      C for 3 to 7 days. Routine mycological techniques were applied to identification
      of grown fungi. RESULTS: Out of 240 plates, 77.5% were positive for fungal
      growth. Twelve different genera were identified. Aspergillus (29.7%),
      Cladosporium (26.7%) and Penicillium (23.9%) were the most common isolated. Among
      Aspergillus species, A. flavus had the highest frequency. Highest colony counts
      were found in autumn. Aspergillus predominated in autumn, Cladosporium in winter
      and spring and Penicillium in summer. CONCLUSION: The results of our study showed
      that hospital water should be considered as a potential reservoir of fungi
      particularly Aspergillus.

PMID- 24451497
TI  - [Quality controls in medical mycology].
AB  - The Quality Management System in medical mycology refers to the systematic
      monitoring with internal and external quality controls: it needs to be organized
      in the laboratory. ISO 15189 standard is not precise in how to demonstrate the
      correctness of tests, in terms of frequency and requirements for quality controls
      QC. That's why the COFRAC, the French Accreditation Committee has published
      guides to which we should refer. The laboratory has to apply internal Quality
      Control Programs. They consist of various tests to check the reagents including
      the culture media. Reference strains have to be provided and preparations of
      homemade reagents are needed, because few are commercialized. Maintaining the
      competence of the technical staff through identification of unknown strains is
      also required. In the fungal serology field, home made antibodies with pooled
      sera or antigen controls are needed. This monitoring has to follow the
      recommandations from the Cofrac technical guide LAB GTA 06. For quantitative
      analysis, the Levey-Jennings chart is a graph with quality control data plotted
      on to give a visual indication. Some external QC references, besides the national
      quality control AFSSAPS, are available. Data evaluation, corrective actions in
      case of out of range results and preventive actions have to be determined in the
      Quality System documents and presented in the annual management review. 

PMID- 24451499
TI  - Cases of tinea capitis as encountered in a private practice laboratory from
      Jordan.
AB  - Tinea capitis is of health concern in many Middle Eastern countries. This study
      reports on the etiologic agents as well as certain demographic factors of tinea
      capitis cases encountered in a medical laboratory. Over a period of 6 years, a
      total of 39 patients were referred to the Medical Diagnostic Laboratories for the
      diagnosis of tinea capitis. Hair and scalp scales were collected and examined
      microscopically using 10% KOH wet mount and by culture using Sabouraud dextrose
      agar. Twenty-five (64.1%) cases were positive for fungal elements by direct
      microscopy, whereas 30 cases (76.9%) were positive for dermatophytes by culture.
      Age of patients with positive cultures varied from 4 to 18 years, with the
      majority of cases (86.7%) occurring in children below 14 years. The isolated
      etiologic agents were T. violaceum (14), M. canis (eight), T. verrucosum (three),
      T. tonsurans (three) and T. schoenleinii (two). However, this communication
      clearly demonstrates that mycological work in medical laboratories in Jordan is
      very limited; it provides an idea about certain epidemiological aspects of tinea
      capitis in the country. It also emphasizes the need for prospective
      investigations at a national level to determine the true incidence of tinea
      capitis. 

PMID- 24451498
TI  - Seven imported histoplasmosis cases due to Histoplasma capsulatum var.
      capsulatum: From few weeks to more than three decades asymptomatic period.
AB  - Histoplasma capsulatum is a nonendemic fungus in Europe. Epidemiological,
      clinical biological features and follow-up of seven imported cases in France were
      reported. These cases underlined the difficulties of such diagnosis in nonendemic
      areas due to greatly variable asymptomatic period, and lack of specific clinical
      signs. Thus, anamnesis should be carefully analysed; mucocutaneous signs and
      immunosuppression should be systematically investigated. Biological diagnosis
      requires multiple sites sampling and long-term conservation of culture medium. 

PMID- 24451500
TI  - [Seasonal and geographical variation range of antifungal activity of sponge
      extracts from the Moroccan Atlantic coasts].
AB  - Currently, marine organisms have a very important source of new molecules in
      pharmacology and thus in the development of new bioactive products. The organic
      and aqueous extracts of two marine sponges, Cinachyrella tarentine collected
      during two different seasons, winter and summer, and Cliona viridis collected in
      two different zones on the coast of El Jadida (Morocco) were tested for their
      antifungal activity using the diffusion method. The C. tarentine sponge collected
      in January (winter) has a very important activity compared to that collected in
      August (summer). While the sponge C. viridis collected from Jorf Lasfar port
      (shallower and polluted area) has a very important activity compared to that
      collected from the coast of El Jadida (depth and unpolluted area). 

PMID- 24451501
TI  - Coccidioidomycosis in India: Report of a third imported case.
AB  - We describe the third fatal case of imported coccidioidomycosis in India in a 31
      year-old mechanical engineer originally from Andhra Pradesh, India, who lived in
      Gwinner, North Dakota. He had traveled to Arizona in summer of 2006, where he
      drove tractors in a dusty environment at a tractor production facility near
      Phoenix, Arizona. He was human immunodeficiency virus (HIV) positive. Initially,
      he was treated in Fargo, North Dakota, in 2006, with liposomal amphotericin B
      followed by oral fluconazole. Antiretroviral treatment for HIV infection was
      started. He moved back to India and was admitted to the intensive care unit of
      St. John's Medical College and Hospital, Bangalore, India. His blood cultures
      yielded Coccidioides sp. The identity of the isolate was confirmed using the Gen
      Probe Accuprobe test at the Centers for Disease Control and Prevention, Atlanta,
      Georgia. In spite of initiation of treatment with antifungal agents (amphotericin
      B and fluconazole), his condition deteriorated and he expired three days
      following his admission to the hospital. 

PMID- 24451502
TI  - Basidiobolomycosis: Case series.
AB  - BACKGROUND: Basidiobolus ranarum is a fungus found in the dung of amphibians,
      reptiles and insectivorous bats. Basidiobolomycosis is a chronic subcutaneous
      infection of the trunk and limbs caused by B. ranarum. The disease is a well
      known infection in the tropical areas. It usually presents with subcutaneous or
      gastrointestinal lesions and rarely with systemic affection. Recently, the
      etiologic role of B. ranarum in the gastrointestinal infections has been
      increasingly recognized. PATIENTS AND METHODS: Here, we retrospectively reviewed
      the records of five patients with basidiobolomycosis, all from the same
      geographic region (Tohama area, Aseer province, southern region of the Kingdom of
      Saudi Arabia). RESULTS: All the cases presented with prolonged fever and other
      manifestations suggestive of either chronic infection (such as tuberculosis) or
      malignancies (such as lymphoma). The diagnosis of gastrointestinal
      basidiobolomycosis was established on histolological ground (granulomatous
      reaction, dense infiltrate of eosinophils and fungal structures). One case was
      diagnosed based on the histological features combined with positive tissue
      culture for B. ranarum. One case was treated by surgical resection of fungal
      masses (Case I), followed by itraconazole and amphoterecin-B therapy. The other
      four cases had non-resectable fungal masses and they responded very well for
      antifungal therapy (cases II, III, and IV received amphotericin-B and
      itraconazole and case V received amphotericin-B and voriconazole). CONCLUSIONS:
      Our study raises several notions. Gastrointestinal basidiobolomycosis is often
      misdiagnosed as cancer (lymphoma or carcinoma), tuberculosis or inflammatory
      bowel disease. Its recognition needs high index of suspicion and increased
      awareness especially in patients with chest, abdominal or neck masses and
      eosinophilia. The diagnosis of basidiobolomycosis can be established on
      histological basis in most cases. The fungal morphology and the Splendore-Hoeppli
      phenomenon are characteristic histological features of this condition. There are
      no prominent risk factors. Usually, surgery and prolonged antifungal therapy are
      required.

PMID- 24451503
TI  - [Interaction between azole antifugals drugs and tacrolimus in four kidney
      transplant patients].
AB  - Tacrolimus, an immunosuppressor indicated in solid organ transplantation, has a
      large inter- and intra-individual variability, a narrow therapeutic index and
      numerous drug interactions. It is metabolized in the enterocytes and the liver by
      CYP3A4. Association to enzymatic inhibitors like azole antifungals increase its
      blood levels and may increase its toxicity directly related to an increase of its
      blood concentration. We describe in this study four cases of drug interaction
      between tacrolimus and azole antifungals. These patients were renal transplanted
      in 2009 and treated with tacrolimus. For fungal infections, azole antifungals
      were added in these cases. Three were treated by fluconazole and one with
      voriconazole. By the risk of drug interaction occurrence, tacrolimus doses were
      decreased by two thirds in one case and by the third in the second case. This
      association leaded to an increase in tacrolimus concentration (1.33 to 2.45 times
      the initial concentration) in all patients. Side effects observed in our patients
      were liver toxicity in two cases, an increase in serum creatinin and an
      hyperglycemia were notified in all patients. An increase in tacrolimus
      concentration with about 1.33 times was observed in the case receiving
      fluconazole intravenously at the dose of 100mg one day out of two and with a
      tacrolimus doses decrease by two thirds. The patient had impaired renal function
      before fluconazole introduction. This suggests that in the presence of renal
      function alteration even low doses of fluconazole with an inhibition of only
      liver CYPA3A4 (without inhibition of intestinal CYP3A4 and P-gp) leads to an
      increase on tacrolimus concentration and occurrence of adverse effects related to
      tacrolimus toxicity. With the co-administration of azole antifugals, it is
      recommended to adjust tacrolimus dosage on the basis of therapeutic tacrolimus
      blood monitoring in order to maintain tacrolimus concentration in therapeutic
      range and to avoid adverse toxic effects. 

PMID- 24451504
TI  - [Rhinofacial mucormycosis: A case report].
AB  - INTRODUCTION: Mucormycosis is the third among deep fungal opportunistic
      infections after candidiasis and aspergillosis. It is a rare fungal infection in
      children, but often fatal, which occurs in immunocompromised patients. It is
      caused by fungi belonging to the order of mucorales. It causes extensive damage
      and decaying soft parts. The authors report the case of a sinonasal mucormycosis
      with fatal outcome in a child suffering from hemophagocytic syndrome. REPORT: PL,
      aged 23 months, resulting from non-consanguineous parents, hospitalized for
      management of hemophagocytic syndrome lasting for 2 months suspected on clinical
      and biological data. This diagnosis was confirmed on histology. The etiological
      diagnosis was negative. A broad-spectrum antibiotics and corticosteroids was
      introduced. A month later, the patient developed necrotic lesions in the nose and
      facing the right maxillary sinus. CT scan of facial mass objectived
      ethmoidomaxillary bilateral sinusitis. The mycological examination of a nasal
      swab showed the presence of non-compartmentalized hyphae, culture on Sabouraud
      chloramphenicol medium without actidione at 37 degrees C isolated Absidia
      corymbifera. Treatment with amphotericin B was initiated but not tolerated. The
      negative trend was rapidly leading to death. CONCLUSION: Rhinocerebral
      mucormycosis is a rare fungal infection in children, we must know how to keep it
      in mind. The mycological examination and/or histology of a local levy allows
      rapid diagnosis. Treatment should be initiated urgently to improve the prognosis.

PMID- 24451505
TI  - [Primitive aspergillosis of the posterior cerebral fossa in immunocompetent
      patient].
AB  - Cerebral aspergillosis arises in the great majority of cases during an invasive
      aspergillosis with hematogene scattering from the lung hurts. The cerebral, not
      rare location is one of the worse criteria forecast during the invasive
      aspergillosis. We report the case of patient who was hospitalized in the
      neurosurgery department for syndrome of increased intracranial pressure,
      hemiparesis and cerebellar syndrome in febrile context. The radiological
      exploration objectified a collection of the posterior fossa. A stereotactic
      biopsy was performed. It collected fragments biopsy and pus. The pathological and
      microbiological analysis allowed the identification of Aspergillus fumigatus. The
      originality of this observation comes from the rare location in the posterior
      fossa of aspergillosis and because the patient is immunocompetent and no primary
      location is found. The patient presents however a viral hepatitis B of fortuitous
      discovery. He is put under treatment by amphotericin B. The evolution is marked
      by meningitis comment-diversion. Antibiotics are prescribed, and then the patient
      is operated for total ablation of the tumor. He dies following an osmolar coma
      associated with thrombopenia and a secondary renal insufficiency due to his
      treatment by the amphotericin B. 

PMID- 24451506
TI  - [Disseminated histoplasmosis due to Histoplasma capsulatum var. duboisii in
      Senegal. A case in HIV-infected patient].
AB  - INTRODUCTION: Histoplasmosis, a disease due to Histoplasma capsulatum, is an
      invasive opportunistic fungal infection, endemic in Africa. So, the occurrence of
      african histoplasmosis associated with HIV infection has been rarely reported
      despite the high prevalence of both pathogens in this area. We report the first
      case of disseminated african histoplasmosis in an HIV-infected Senegalese
      patient. OBSERVATION: A patient, 50-year-old has been admitted for umbilicate,
      necrotic and disseminated papulonodular lesions with oral infection, fever and
      reduction of total body mass. HIV1 test was positive, and CD4 count was 4/mm(3).
      Direct examination of ulcerated lesions shown extracellular, large, doubly
      contoured yeasts. After culture, we obtain brownish colonies, septate hyphae,
      echinulated chlamydospores characteristic of Histoplasma. Cutaneous biopsy
      revealed polymorphous granulomatous infiltrate, giant cells containing numerous
      large, doubly contoured, thick-wall yeast-bodies characteristic of H. capsulatum
      var. duboisii. DISCUSSION: The association AIDS and histoplasmosis frequency is
      probably underestimated because the difficult diagnosis and the ignorance of the
      medical staff.

PMID- 24451507
TI  - Don't stop the quest to measure Big G.

PMID- 24451519
TI  - Budget offers recovery hope.

PMID- 24451520
TI  - Polar drilling problems revealed.

PMID- 24451521
TI  - Rock's power to mop up carbon revisited.

PMID- 24451522
TI  - Yellowstone grizzlies face losing protected status.

PMID- 24451523
TI  - Sea drilling project launches.

PMID- 24451524
TI  - Cloning comeback.

PMID- 24451525
TI  - Quantum physics: flawed to perfection.

PMID- 24451529
TI  - Land management: Weighing up reuse of Soviet croplands.

PMID- 24451530
TI  - Land management: Resolving soil pollution in China.

PMID- 24451531
TI  - Reproducibility: Fraud is not the big problem.

PMID- 24451532
TI  - Immunotherapy: Natural killers take on cancer.

PMID- 24451533
TI  - Peer review: Payback time for referee refusal.

PMID- 24451534
TI  - Sexism: Editor's note.

PMID- 24451535
TI  - Janet Rowley (1925-2013).

PMID- 24451536
TI  - Solar system: Evaporating asteroid.

PMID- 24451537
TI  - Stem cells: Sex specificity in the blood.

PMID- 24451539
TI  - Climate science: A resolution of the Antarctic paradox.

PMID- 24451540
TI  - HIV: Not-so-innocent bystanders.

PMID- 24451541
TI  - Localized sources of water vapour on the dwarf planet (1) Ceres.
AB  - The 'snowline' conventionally divides Solar System objects into dry bodies,
      ranging out to the main asteroid belt, and icy bodies beyond the belt. Models
      suggest that some of the icy bodies may have migrated into the asteroid belt.
      Recent observations indicate the presence of water ice on the surface of some
      asteroids, with sublimation a potential reason for the dust activity observed on
      others. Hydrated minerals have been found on the surface of the largest object in
      the asteroid belt, the dwarf planet (1) Ceres, which is thought to be
      differentiated into a silicate core with an icy mantle. The presence of water
      vapour around Ceres was suggested by a marginal detection of the
      photodissociation product of water, hydroxyl (ref. 12), but could not be
      confirmed by later, more sensitive observations. Here we report the detection of
      water vapour around Ceres, with at least 10(26) molecules being produced per
      second, originating from localized sources that seem to be linked to mid-latitude
      regions on the surface. The water evaporation could be due to comet-like
      sublimation or to cryo-volcanism, in which volcanoes erupt volatiles such as
      water instead of molten rocks.

PMID- 24451542
TI  - Impacts of the north and tropical Atlantic Ocean on the Antarctic Peninsula and
      sea ice.
AB  - In recent decades, Antarctica has experienced pronounced climate changes. The
      Antarctic Peninsula exhibited the strongest warming of any region on the planet,
      causing rapid changes in land ice. Additionally, in contrast to the sea-ice
      decline over the Arctic, Antarctic sea ice has not declined, but has instead
      undergone a perplexing redistribution. Antarctic climate is influenced by, among
      other factors, changes in radiative forcing and remote Pacific climate
      variability, but none explains the observed Antarctic Peninsula warming or the
      sea-ice redistribution in austral winter. However, in the north and tropical
      Atlantic Ocean, the Atlantic Multidecadal Oscillation (a leading mode of sea
      surface temperature variability) has been overlooked in this context. Here we
      show that sea surface warming related to the Atlantic Multidecadal Oscillation
      reduces the surface pressure in the Amundsen Sea and contributes to the observed
      dipole-like sea-ice redistribution between the Ross and Amundsen-Bellingshausen
      Weddell seas and to the Antarctic Peninsula warming. Support for these findings
      comes from analysis of observational and reanalysis data, and independently from
      both comprehensive and idealized atmospheric model simulations. We suggest that
      the north and tropical Atlantic is important for projections of future climate
      change in Antarctica, and has the potential to affect the global thermohaline
      circulation and sea-level change. 

PMID- 24451543
TI  - Oestrogen increases haematopoietic stem-cell self-renewal in females and during
      pregnancy.
AB  - Sexually dimorphic mammalian tissues, including sexual organs and the brain,
      contain stem cells that are directly or indirectly regulated by sex hormones. An
      important question is whether stem cells also exhibit sex differences in
      physiological function and hormonal regulation in tissues that do not show sex
      specific morphological differences. The terminal differentiation and function of
      some haematopoietic cells are regulated by sex hormones, but haematopoietic stem
      cell function is thought to be similar in both sexes. Here we show that mouse
      haematopoietic stem cells exhibit sex differences in cell-cycle regulation by
      oestrogen. Haematopoietic stem cells in female mice divide significantly more
      frequently than in male mice. This difference depends on the ovaries but not the
      testes. Administration of oestradiol, a hormone produced mainly in the ovaries,
      increased haematopoietic stem-cell division in males and females. Oestrogen
      levels increased during pregnancy, increasing haematopoietic stem-cell division,
      haematopoietic stem-cell frequency, cellularity, and erythropoiesis in the
      spleen. Haematopoietic stem cells expressed high levels of oestrogen receptor
      alpha (ERalpha). Conditional deletion of ERalpha from haematopoietic stem cells
      reduced haematopoietic stem-cell division in female, but not male, mice and
      attenuated the increases in haematopoietic stem-cell division, haematopoietic
      stem-cell frequency, and erythropoiesis during pregnancy. Oestrogen/ERalpha
      signalling promotes haematopoietic stem-cell self-renewal, expanding splenic
      haematopoietic stem cells and erythropoiesis during pregnancy. 

PMID- 24451545
TI  - The effect of rising obesity on eligibility to serve in the U.S. Public Health
      Service Commissioned Corps.
AB  - This study investigates how rising obesity has affected eligibility to serve in
      the United States Public Health Service Commissioned Corps (PHSCC), the uniformed
      service charged with protecting and promoting public health in the U.S. Data are
      drawn from the National Health and Nutrition Examination Surveys. Between 1959
      and 2010, the percentage of eligible civilians who exceed the weight-for-height
      and body fat standards of the PHSCC rose from 9.05% to 18.24% among men, and from
      6.13% to 23.10% among women. Simulations indicate that a further 1% increase in
      population body weight will result in an additional 3.42% of men and 5.08% of
      women exceeding PHSCC accession standards. This study documents an under
      appreciated consequence of the rise in obesity: fewer Americans eligible to
      develop and implement a public health response to obesity through the PHSCC. This
      illustrates how a public health problem can undermine the public health labor
      force, compromising a response and risking a self-reinforcing trend. These
      findings are timely as the Patient Protection and Affordable Care Act (ACA) calls
      for a major expansion of the PHSCC. 

PMID- 24451546
TI  - Genetic and physical interaction of Ssp1 CaMKK and Rad24 14-3-3 during low pH and
      osmotic stress in fission yeast.
AB  - The Ssp1 calmodulin kinase kinase (CaMKK) is necessary for stress-induced re
      organization of the actin cytoskeleton and initiation of growth at the new cell
      end following division in Schizosaccharomyces pombe. In addition, it regulates
      AMP-activated kinase and functions in low glucose tolerance. ssp1(-) cells
      undergo mitotic delay at elevated temperatures and G2 arrest in the presence of
      additional stressors. Following hyperosmotic stress, Ssp1-GFP forms transient
      foci which accumulate at the cell membrane and form a band around the cell
      circumference, but not co-localizing with actin patches. Hyperosmolarity-induced
      localization to the cell membrane occurs concomitantly with a reduction of its
      interaction with the 14-3-3 protein Rad24, but not Rad25 which remains bound to
      Ssp1. The loss of rad24 in ssp1(-) cells reduces the severity of hyperosmotic
      stress response and relieves mitotic delay. Conversely, overexpression of rad24
      exacerbates stress response and concomitant cell elongation. rad24(-) does not
      impair stress-induced localization of Ssp1 to the cell membrane, however this
      response is almost completely absent in cells overexpressing rad24. 

PMID- 24451547
TI  - Cross-talk between Rho and Rac GTPases drives deterministic exploration of
      cellular shape space and morphological heterogeneity.
AB  - One goal of cell biology is to understand how cells adopt different shapes in
      response to varying environmental and cellular conditions. Achieving a
      comprehensive understanding of the relationship between cell shape and
      environment requires a systems-level understanding of the signalling networks
      that respond to external cues and regulate the cytoskeleton. Classical
      biochemical and genetic approaches have identified thousands of individual
      components that contribute to cell shape, but it remains difficult to predict how
      cell shape is generated by the activity of these components using bottom-up
      approaches because of the complex nature of their interactions in space and time.
      Here, we describe the regulation of cellular shape by signalling systems using a
      top-down approach. We first exploit the shape diversity generated by systematic
      RNAi screening and comprehensively define the shape space a migratory cell
      explores. We suggest a simple Boolean model involving the activation of Rac and
      Rho GTPases in two compartments to explain the basis for all cell shapes in the
      dataset. Critically, we also generate a probabilistic graphical model to show how
      cells explore this space in a deterministic, rather than a stochastic, fashion.
      We validate the predictions made by our model using live-cell imaging. Our work
      explains how cross-talk between Rho and Rac can generate different cell shapes,
      and thus morphological heterogeneity, in genetically identical populations. 

PMID- 24451548
TI  - Anillin-dependent organization of septin filaments promotes intercellular bridge
      elongation and Chmp4B targeting to the abscission site.
AB  - The final step of cytokinesis is abscission when the intercellular bridge (ICB)
      linking the two new daughter cells is broken. Correct construction of the ICB is
      crucial for the assembly of factors involved in abscission, a failure in which
      results in aneuploidy. Using live imaging and subdiffraction microscopy, we
      identify new anillin-septin cytoskeleton-dependent stages in ICB formation and
      maturation. We show that after the formation of an initial ICB, septin filaments
      drive ICB elongation during which tubules containing anillin-septin rings are
      extruded from the ICB. Septins then generate sites of further constriction within
      the mature ICB from which they are subsequently removed. The action of the
      anillin-septin complex during ICB maturation also primes the ICB for the future
      assembly of the ESCRT III component Chmp4B at the abscission site. These studies
      suggest that the sequential action of distinct contractile machineries
      coordinates the formation of the abscission site and the successful completion of
      cytokinesis. 

PMID- 24451550
TI  - Impact of psychosocial factors on functional improvement in Latino older adults
      after Tai Chi exercise.
AB  - Increasing evidence underscores the health benefits of Tai Chi (TC), although
      there is limited evidence of benefits among racial and ethnic minorities. This
      study investigated the impact of psychosocial status on balance among 23 Latino
      seniors after a twice-a-week, 12-week TC exercise program. Functional status was
      measured at baseline, immediately after, and three months following the TC
      exercise program, using the Timed Up and Go Test and Tinetti Falls Efficacy
      Scale. Psychosocial status was measured at baseline by the Center for
      Epidemiologic Studies Depression Scale and Norbeck Social Support Questionnaire.
      Both measures of functional status improved and were sustained after three months
      of TC. Greater improvement was significantly related to a higher level of
      baseline social support. More depressed seniors reported less fear of falling
      after TC. Depression and social support are important moderators of functional
      improvement after TC among Latino seniors. 

PMID- 24451551
TI  - Utilizing optical coherence tomography in diagnosing a unique presentation of
      chiasmal hypoplasia variant of septo-optic dysplasia.

PMID- 24451549
TI  - A novel O-linked glycan modulates Campylobacter jejuni major outer membrane
      protein-mediated adhesion to human histo-blood group antigens and chicken
      colonization.
AB  - Campylobacter jejuni is an important cause of human foodborne gastroenteritis;
      strategies to prevent infection are hampered by a poor understanding of the
      complex interactions between host and pathogen. Previous work showed that C.
      jejuni could bind human histo-blood group antigens (BgAgs) in vitro and that
      BgAgs could inhibit the binding of C. jejuni to human intestinal mucosa ex vivo.
      Here, the major flagella subunit protein (FlaA) and the major outer membrane
      protein (MOMP) were identified as BgAg-binding adhesins in C. jejuni NCTC11168.
      Significantly, the MOMP was shown to be O-glycosylated at Thr(268); previously
      only flagellin proteins were known to be O-glycosylated in C. jejuni.
      Substitution of MOMP Thr(268) led to significantly reduced binding to BgAgs. The
      O-glycan moiety was characterized as Gal(beta1-3)-GalNAc(beta1-4)-GalNAc(beta1-4)
      GalNAcalpha1-Thr(268); modelling suggested that O-glycosylation has a notable
      effect on the conformation of MOMP and this modulates BgAg-binding capacity.
      Glycosylation of MOMP at Thr(268) promoted cell-to-cell binding, biofilm
      formation and adhesion to Caco-2 cells, and was required for the optimal
      colonization of chickens by C. jejuni, confirming the significance of this O
      glycosylation in pathogenesis. 

PMID- 24451552
TI  - The 25th reunion of CLAN, the Latin American Neuro-Ophthalmology Club.

PMID- 24451554
TI  - Non-Abelian gapless and quasi-gapless excitations of vortices in condensed matter
      systems.
AB  - We discuss the low energy effective theory of gapless excitations of the mass
      vortices of systems similar to the Ginzburg-Landau description of superfluid
      helium-3 in the bulk B-phase. Our approach is to determine the vortex solution by
      considering a specific ansatz for the order parameter and minimizing the free
      energy. The conditions on the betai coefficients required for the stability of
      the various solutions for the order parameter are calculated. By considering the
      symmetries that are broken by the vortex solutions we are able to generate the
      modulus fields associated with the low energy excitations of the vortices. Using
      these fields we determine the effective free energy describing the dynamics of
      these excitations. 

PMID- 24451553
TI  - Analysis of maternal microchimerism in rhesus monkeys (Macaca mulatta) using real
      time quantitative PCR amplification of MHC polymorphisms.
AB  - Although pregnancy-associated microchimerism is known to exist in humans, its
      clinical significance remains unclear. Fetal microchimerism has been documented
      in rhesus monkeys, but the trafficking and persistence of maternal cells in the
      monkey fetus and infant have not been fully explored. To investigate the
      frequency of maternal microchimerism in the rhesus monkey (Macaca mulatta), a
      real-time polymerase chain reaction (PCR) strategy was developed and validated to
      target polymorphic major histocompatibility complex (MHC) gene sequences.
      Informative PCR assays were identified for 19 of 25 dams and their respective
      offspring. Analyses were performed on tissues (thymus, liver, spleen, lymph
      nodes, and bone marrow) and peripheral blood mononuclear cells (PBMCs) collected
      prenatally and postnatally in a subset of animals. Seven of 19 monkeys had
      detectable maternal microchimerism in at least one compartment (range: 0.001-1.9%
      chimeric cells). In tissues, maternal microchimerism was found in 2 of 7 fetuses
      and 3 of 12 juveniles (1-1.5 years of age), and most of the animals that were
      positive had microchimeric cells in more than one tissue. Maternal microchimerism
      was detected in PBMCs from all (4 of 4) fetuses. These observations suggest that
      maternal microchimerism occurs in the rhesus monkey fetus and can be detected in
      tissues in a subset of offspring after birth. 

PMID- 24451555
TI  - Enhancing capacity for risk factor surveillance at the regional/local level: a
      follow-up review of the findings of the Canadian Think Tank Forum after 4 years.
AB  - BACKGROUND: National health surveys are sometimes used to provide estimates on
      risk factors for policy and program development at the regional/local level.
      However, as regional/local needs may differ from national ones, an important
      question is how to also enhance capacity for risk factor surveillance
      regionally/locally. METHODS: A Think Tank Forum was convened in Canada to discuss
      the needs, characteristics, coordination, tools and next steps to build capacity
      for regional/local risk factor surveillance. A series of follow up activities to
      review the relevant issues pertaining to needs, characteristics and capacity of
      risk factor surveillance were conducted. RESULTS: Results confirmed the need for
      a regional/local risk factor surveillance system that is flexible, timely, of
      good quality, having a communication plan, and responsive to local needs. It is
      important to conduct an environmental scan and a gap analysis, to develop a
      common vision, to build central and local coordination and leadership, to build
      on existing tools and resources, and to use innovation. CONCLUSIONS: Findings of
      the Think Tank Forum are important for building surveillance capacity at the
      local/county level, both in Canada and globally. This paper provides a follow-up
      review of the findings based on progress over the last 4 years.

PMID- 24451556
TI  - The use of antipsychotics in preschoolers: a veto or a sensible last option?
AB  - Recent reports have illustrated a dramatic rise in the use of antipsychotics in
      preschool children, medications originally designed and licensed for the
      treatment of adult psychotic disorders. Within this context, the current usage
      and the associated diagnoses are reviewed and compared with official guidelines
      and licensing for such use, highlighting a controversial challenge for
      clinicians. A review of the evidence base of the relative efficacy of such
      medications for a range of disorders is given. Associated safety and side effects
      are discussed, with compelling evidence for increased adverse events associated
      with use of antipsychotics in preschoolers, and neurodevelopmental hypotheses are
      used to guide predictions of long-term risk. An apparent gap in the literature
      and evidence base supporting such use and elucidating the risks and benefits
      leaves a challenge for clinicians and researchers and hinders the development of
      appropriate guidelines. Pragmatism in clinical practice, mindful of the limited
      evidence base that does exist and the propensity for harm, is necessary; far more
      research is required in this important area. 

PMID- 24451557
TI  - [Survey on the medical mycology processes to the members of the French Society
      for Medical Mycology].
AB  - AIM OF THE STUDY: The objective of the survey was to describe the practices of
      clinical laboratories in terms of cultures in medical mycology. We have
      implemented this project within the members of the French Society for Medical
      Mycology (SFMM) to evaluate the analytical processes of the mycological
      examination in our laboratories. This preliminary study would help to suggest the
      future French guidelines. MATERIALS AND METHODS: A questionnaire regarding the
      processing of mycology analysis was sent to the 227 members of the SFMM in 2009.
      The data involved 21 types of samples, direct microscopic examination with or
      without colouring and the reagents, the number of culture media, the types of
      media (Sabouraud, Sabouraud antibiotic, Sabouraud cycloheximide and chromogenic
      medium), temperature and duration of the incubation (days) and the existence of a
      first result before the end of the incubation period. The analytical processes
      were compared to an accredited laboratory according to EN ISO 15189. RESULTS: A
      great heterogeneity was observed in the 36 forms from 27 (75%) laboratories
      belonging to university hospitals among the 38 existing in France. As for deep
      samples, two microscopic exams were performed, only one was usually done. A more
      sensitive technique was preferred to the wet-mount for some samples. Routine
      samples are often inoculated on a chromogenic media. For deep samples two medium
      are inoculated (chromogenic media, Sabouraud and antibiotics). If the temperature
      of incubation is unique, 30 degrees C was chosen. A temperature of 37 degrees C
      was preferred for samples where Candida spp. is selected. When there are two
      temperatures of incubation, 27 degrees C and 37 degrees C were preferred.
      CONCLUSION: Each biologist can compare his proceedings to the other laboratories
      and to a laboratory already accredited. The question is to find the best
      strategies for each medical mycology specimen. They will aid the process of
      accreditation according to EN ISO 15189, which now applies in all laboratories in
      Europe.

PMID- 24451558
TI  - Antifungal activity of Pterocaulon species (Asteraceae) against Sporothrix
      schenckii.
AB  - Plants of the genus Pterocaulon (Asteraceae) are popularly used in the treatment
      of skin diseases caused by fungi and bacteria. The aim of this work was to
      investigate the in vitro activity of the crude methanolic extracts obtained from
      the aerial parts of Pterocaulon polystachyum, P. balansae, P. lorentzii, P.
      lanatum, and P. cordobense against 24 Sporothrix schenckii clinical isolates and
      determine the minimum inhibitory concentration (MIC) and the minimum fungicidal
      concentration (MFC). MIC were performed by the broth microdilution method
      according guidelines recommended by Clinical and Laboratory Standards Institute
      for filamentous fungi and MFC were determined for transference of aliquots of the
      well that showed 100% of growth inhibition into tubes with culture medium. The
      extract from P. polystachyum was the most active sample, presenting MIC range of
      156 and 312MUg/mL. The popular use of these plants corroborates the importance of
      ethnopharmacological surveys and opens the possibility for finding new clinically
      effective antifungal agents. 

PMID- 24451559
TI  - [Mycetomas diagnosed in Senegal from 2008 to 2010].
AB  - INTRODUCTION: Mycetomas are inflammatory pseudotumours of subcutaneous and
      possibly osseous soft fabrics, generally polyfistulas with chronic mode of
      evolution. PATIENTS AND METHODS: This study was carried out at the laboratory of
      parasitology and mycology of Le Dantec hospital in Dakar, Senegal, including 113
      patients, from june 2008 to july 2010. RESULTS: Patients were from different
      regions in Senegal and in neighborhood countries, referred to the laboratory for
      mycetoma diagnosis. Among the 250 patients referred, 113 were positives after
      direct observation and culture corresponding to 45.2% index of infestation. The
      age range varies between 13 to 73years with an average age of 33.9years. The age
      bracket ranging between 20-39years is more infected (27.34%), followed by 40
      59years (25.2%), 60years and more (4.5%), 30-39years (16.64%), 13-19years (7.2%).
      The infection sex rate were, male: 79.6% and female: 20.4%. Infection prevalence
      profession dependant was found mainly in farmers and breeders with respectively:
      48.7%, and 42.5%. The foot infestation is most represented with 72.5%, then leg
      (12.3%), knee (7.1%), scalp (2.7%), hand (1.8%). The other localizations are
      found with less than 1%: back, thigh, chest and ganglion inguinal. According to
      mycetoma agents, fungy are represented than mycetomas actinomycosic with
      respectively 70% and 30%. The species found were: Madurella mycetomatis (53.1%),
      Actinomadura pelletieri (23%), Leptosphaeria senegalensis (9.7%), Streptomyces
      somaliensis (2.6%), Actinomadura madurae (2,6%), Pseudallescheria boydii (1.8%),
      Nocardia spp. (1.8%), Scedosporium apiospermum (0.9%), Fusarium solani (0.9%). We
      found agents of dermatophytes: Microsporum langeronii (1.8%), and Trichophyton
      mentagrophytes (0.9%). CONCLUSION: This study confirms that mycetomas are endemic
      affections in Senegal, where it still remain a real cause of disability among
      population leaving in rural area.

PMID- 24451560
TI  - Candida albicans biofilms formed into catheters and probes and their resistance
      to amphotericin B.
AB  - In Algeria, many bacterial biofilms have been studied but those of fungal origin,
      particularly those due to the yeast Candida albicans remained unidentified. The
      present study was performed at the Chabane Hamdoune hospital in Maghnia
      (Algeria), where 51 strains of C. albicans representing 16.94% of all taken
      samples were isolated. They were collected from catheters and probes used in
      different hospital services with variable rates; the most concerned service was
      ICU (40.74%) followed by gynecology department (17.39%), while general surgery
      came third (15.79%). Testing the antifungal property of amphotericin B (AmB) we
      showed clearly that the sessile cells of C. albicans were much more resistant
      than their planktonic counterparts (suspended cells), especially when the
      resistance increased during the different phases of biofilm formation until it
      reached its threshold at the ripening stage (at 48h). Furthermore, scanning
      electron microscopy of the isolated strains in the laboratory revealed the
      formation of biofilms on catheters by C. albicans. Surprisingly, observations
      revealed the presence of a new structure in these biofilms: a chlamydospore? 

PMID- 24451561
TI  - Screening of antimicrobial membrane-active metabolites of soil microfungi by
      using chromatic phospholipid/polydiacetylene vesicles.
AB  - OBJECTIVE: The focus of this study is screening of antimicrobial membrane-active
      metabolites of soil microfungi by using chromatic phospholipid/polydiacetylene
      vesicles. MATERIALS AND METHODS: In this work, soil samples were collected from
      desert, forest, farm, lake shore and mineral zones of Northern and Central parts
      of Iran. These parts were not studied for antimicrobial potential of the soil
      isolates producing metabolites with membrane activity in particular, from
      microfungi. In the primary screening that was performed to evaluate the
      antimicrobial activity, isolates were analyzed in terms of their general
      inhibition effects to indicator strains including Escherichia coli, Candida
      albicans, and Saccharomyces cerevisiae. In the secondary screening, isolates
      producing membrane-active metabolites were determined using a Rapid Chromatic
      Detection method. The chromatic technology is simple and this method provides a
      rapid and easy evaluation of interactions between antimicrobial membrane-active
      metabolites and lipid layers of vesicles as well. RESULTS: A total number of 59
      species of fungi was isolated from the soil samples. It has been found that 20
      isolates were effective against indicator strains. Based on color and
      fluorescence changes that are easily identified by the naked eye and fluorescent
      microscopy and can be recorded by UV-Vis spectrophotometery, one fungus showed
      antimicrobial membrane-activity effect against some of the indicator strains.
      This isolate was identified to the genus level that belonged to Aspergillus.
      CONCLUSION: As resistance is barely developed against membrane-active
      antibiotics, in this paper, we demonstrated the application of the chromatic
      vesicle model for screening of antimicrobial membrane-active metabolites as
      potential new antibiotics from soil microfungi.

PMID- 24451562
TI  - [Dermatomycosis due to Trichophyton verrucosum in Sfax-Tunisia].
AB  - Trichophyton verrucosum is a zoophilic dermatophyte. It can be responsible of
      various clinical aspects especially inflammatory lesions of skin and scalp. The
      aim of this study was to determine the clinical and epidemiological
      characteristics of dermatophytosis due to T. verrucosum. PATIENTS AND METHODS: It
      is a retrospective study realized on 35,918 patients suspected to have
      superficial mycoses in a 13-year-period (from 1998 to 2010). RESULTS: T.
      verrucosum was isolated in 178 patients corresponding to 1.2% of all
      dermatophytosis. Ochraceum variety was the most frequent (60%), followed by album
      variety (40%). Frequency of isolated T. verrucosum increased passing from one
      case in 1998 to 37 cases in 2010. The mean age was 22.7 years (range: 1.5-71
      years). A percentage of 74.2 of our patients were male and 61% were from urban
      regions. A percentage of 32.5 could link their clinical lesions to contact with
      an animal (mainly cattle and sheep). Other family members were infected by tinea
      in 7.3% of cases. Tinea corporis was the most frequent (62.2%), followed by tinea
      capitis (31.6%). Ten cases of sycosis, one case of tinea pedis and one case of
      pubic tinea were diagnosed. Lesions of skin were erythemato-squamous (82.5%) and
      pustulo-inflammatory (17.5%), affecting mainly upper limb (58.3%) and face
      (25.8%). For tinea capitis, lesions were squamous (30.8%) and pustulo
      inflammatory (41%). Eleven cases of kerion celsi were diagnosed (28.2%). Patients
      were affected in one site (79.7%), two sites (16.9%) and three or more (3.4%).
      CONCLUSION: Dermatophytosis due to T. verrucosum is in recrudescence in our
      region. This finding may be explained by changing behaviors and activities of the
      population with a low socioeconomic level who kept a larger number of domestic
      animals at homes.

PMID- 24451563
TI  - [Erysipelas of the face revealing a mucormycosis].
AB  - BACKGROUND: Mucormycosis is an opportunistic fungal infection, typically
      affecting immunocompromised patients. Rhino-orbital location is the most frequent
      form with cerebral blood vessels invasion and a fatal outcome. CASE REPORT: An
      immunocompetent 38-year-old woman, with previous history of primary cutaneous
      mucormycosis, was admitted for a febrile erythemato-oedematous lesion of the face
      with well-demarcated edge evoking erysipelas. No cutaneous portal of entry was
      identified. Oral cavity examination found an ulceronecrotic lesion of the hard
      palate. Diagnosis of mucormycosis was retained after nasal endoscopy and
      histological findings. The patient was first treated for erysipelas, then by
      ascending dose of intravenous amphotericin B. A good outcome was observed despite
      the occurrence of nephrotoxicity which normalized by alkaline hyperhydratation.
      Healing was obtained after 1month of effective dose leaving cleft palate
      sequelae. DISCUSSION: Mucormycosis occurs rarely in immunocompetent, even more if
      it is a second episode. Affecting the face, it may simulate or be revealed by
      superficial skin infection. Within that, a meticulous otorhinolaryngeal
      examination is required when the portal of entry is not obvious.

PMID- 24451564
TI  - [Severe keratomycosis due to Fusarium solani induced by a telluric foreign body:
      About a case in moroccan Sahara].
AB  - We report a case of severe keratitis due to Fusarium solani in a young man in the
      Sahara in Morocco where the climate is arid. This patient reported had a grain of
      sand in his right eye for a week after a sandstorm. On admission he had a corneal
      abscess. Despite rapid diagnosis and initiation of treatment with available
      antifungal drugs: amphotericin B and natamycin eye drops, the prognosis worsened
      and led to the enucleation of the right eye. Faced with a suspected eye infection
      after a microtrauma caused by grains of sand carried by a sandstorm, it is
      important to take biological samples to search for fungal infections among other.
      It is also important to have new triazole antifungal drugs available to treat
      ocular mycosis rapidly and effectively. 

PMID- 24451565
TI  - Probable primary cutaneous histoplasmosis in a patient infected with HIV.
AB  - Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma
      capsulatum. Most infections occur after inhalation of fungal spores. A wide
      variety of clinical manifestations can occur depending on the host response and
      the extent of inoculation. We report a case of probable cutaneous histoplasmosis
      after trauma in a 26-year-old man from Paraguay who was also infected with the
      human immunodeficiency virus. Diagnosis was based on histological and mycological
      examination. No systemic involvement was found. 

PMID- 24451566
TI  - [Auditory hallucinations due to voriconazole: Illustration by plasma monitoring].
AB  - Voriconazole is a second-generation azole antifungal that is widely indicated in
      the treatment of invasive aspergillosis. It is generally well tolerated. It has
      nevertheless numerous side effects like hepatotoxicity, photosensitivity, skin
      rashes, and visual disturbances. Hallucinations were also reported as side
      effects to voriconazole but auditory hallucinations were rarely reported and seem
      to be related to toxic voriconazole blood levels. We report, herein, a case of
      auditory hallucination with monitoring of voriconazole plasma concentration
      during hallucination and after its disappearance. A 38-year-old man was treated
      with intravenously voriconazole for a pulmonary aspergillosis. Seven days after
      the initiation of voriconazole, the patient presented a sudden history of
      auditory hallucination associated to incoherence and temporo-spatial
      disorientation. Therapeutic drug monitoring of voriconazole showed a plasmatic
      residual concentration (C0) of 7.5MUg/mL (therapeutic interval: 1.4-1.8MUg/mL)
      and a pic concentration (Cmax) of 9.83MUg/mL (therapeutic interval: 2.1
      4.8MUg/ml). Voriconazole was then stopped and, two days later, symptomatology
      completely disappeared and at the same time levels of voriconazole decreased
      (C0=0.11MUg/mL and Cmax=2.17MUg/mL). We concluded in our case that the patient's
      auditory hallucinations were caused by voriconazole treatment. In fact, the
      sudden onset of hallucinations was concomitant with high plasmatic voriconazole
      levels, and since the medication was stopped, an important decrease of
      voriconazole levels was observed which was associated with a sudden disappearance
      of the auditory hallucinations. 

PMID- 24451567
TI  - [Parotid mucormycosis: A new case and review of the literature].
AB  - INTRODUCTION: Mucormycosis is a rare, devastating, fungal infection, which
      disproportionately affects non-controlled diabetic patients, notably during
      ketoacidosis. The authors report the case of cervical mucormycoses with a
      particularly favorable evolution in diabetic woman. REPORT: A 54-year-old woman,
      type 2 diabetic, had presented a left lateral cervical mass. The diagnosis was
      confirmed by histological examination. She was treated with Amphotericin B with
      favorable evolution. CONCLUSION: The mucormycose is a rare infection. The
      treatment is medical and surgical. The prognosis is severe with an overall
      mortality rate of 40%.

PMID- 24451568
TI  - Pharmacological characterization of BDNF promoters I, II and IV reveals that
      serotonin and norepinephrine input is sufficient for transcription activation.
AB  - Compelling evidence has shown that the effects of antidepressants, increasing
      extracellular serotonin and noradrenaline as a primary mechanism of action,
      involve neuroplastic and neurotrophic mechanisms. Brain-derived neurotrophic
      factor (BDNF) has been shown to play a key role in neuroplasticity and synaptic
      function, as well as in the pathophysiology of neuropsychiatric disorders and the
      mechanism of action of antidepressants. The expression of BDNF is mediated by the
      transcription of different mRNAs derived by the splicing of one of the eight 5'
      non-coding exons with the 3' coding exon (in rats). The transcription of each non
      coding exon is driven by unique and different promoters. We generated a gene
      reporter system based on hippocampal and cortical neuronal cultures, in which the
      transcription of luciferase is regulated by BDNF promoters I, II, IV or by cAMP
      response element (CRE), to investigate the activation of selected promoters
      induced by monoaminergic antidepressants and by serotonin or noradrenaline
      agonists. We found that incubation with fluoxetine or reboxetine failed to induce
      any activation of BDNF promoters or CRE. On the other hand, the incubation of
      cultures with selective agonists of serotonin or noradrenaline receptors induced
      a specific and distinct profile of activation of BDNF promoters I, II, IV and
      CRE, suggesting that the monoaminergic input, absent in dissociated cultures, is
      essential for the modulation of BDNF expression. In summary, we applied a rapidly
      detectable and highly sensitive reporter gene assay to characterize the selective
      activation profile of BDNF and CRE promoters, through specific and different
      pharmacological stimuli. 

PMID- 24451569
TI  - Plk1 phosphorylates CLIP-170 and regulates its binding to microtubules for
      chromosome alignment.
AB  - The microtubule (MT) cytoskeleton is essential for cellular morphogenesis, cell
      migration, and cell division. MT organization is primarily mediated by a variety
      of MT-associated proteins. Among these proteins, plus-end-tracking proteins
      (+TIPs) are evolutionarily conserved factors that selectively accumulate at
      growing MT plus ends. Cytoplasmic linker protein (CLIP)-170 is a +TIP that
      associates with diverse proteins to determine the behavior of MT ends and their
      linkage to intracellular structures, including mitotic chromosomes. However, how
      CLIP-170 activity is spatially and temporally controlled is largely unknown.
      Here, we show that phosphorylation at Ser312 in the third serine-rich region of
      CLIP-170 is increased during mitosis. Polo-like kinase 1 (Plk1) is responsible
      for this phosphorylation during the mitotic phase of dividing cells. In vitro
      analysis using a purified CLIP-170 N-terminal fragment showed that
      phosphorylation by Plk1 diminishes CLIP-170 binding to the MT ends and lattice
      without affecting binding to EB3. Furthermore, we demonstrate that during
      mitosis, stable kinetochore/MT attachment and subsequent chromosome alignment
      require CLIP-170 and a proper phosphorylation/dephosphorylation cycle at Ser312.
      We propose that CLIP-170 phosphorylation by Plk1 regulates proper chromosome
      alignment by modulating the interaction between CLIP-170 and MTs in mitotic cells
      and that CLIP-170 activity is stringently controlled by its phosphorylation
      state, which depends on the cellular context. 

PMID- 24451572
TI  - Shortened stapedius tendon: a rare cause of conductive hearing loss.
AB  - INTRODUCTION: Anomalies of the stapedius tendon have been reported to cause
      conductive hearing loss; in theory, such anomalies limit the movement of the
      stapes. OBJECTIVES: To demonstrate a rare cause of conductive hearing loss
      resulting from anomaly of the stapedius tendon and to compare the clinical
      findings of this patient to other stapedius tendon anomalies reported in the
      literature. METHOD: Case report of a single case of shortened stapedius tendon
      and a review of the English literature on stapedius tendon anomalies. RESULTS:
      This is a case report of a 15-year-old boy with shortened stapedius tendon
      causing unilateral hearing loss, accompanied by a review of the literature.
      Contrary to other reported cases, this patient did not have an ossified tendon,
      but rather an extremely short tendon. The boy regained normal hearing following
      excision of the stapedius tendon. CONCLUSION: A shortened stapedius tendon is a
      very rare diagnosis, yet it should be considered as a possible cause of
      conductive hearing loss.

PMID- 24451573
TI  - The bean counters are coming!

PMID- 24451579
TI  - Natural product biosynthesis: It's all downhill from here.

PMID- 24451580
TI  - Enzymatic C-H bond activation: Using push to get pull.

PMID- 24451581
TI  - Graphene synthesis: Nanoribbons from the bottom-up.

PMID- 24451582
TI  - Chemical biology: Knockout for malaria.

PMID- 24451583
TI  - C-H Activation: A surrogate for selectivity.

PMID- 24451584
TI  - Hollow nanotubular toroidal polymer microrings.
AB  - Despite the remarkable progress made in the self-assembly of nano- and microscale
      architectures with well-defined sizes and shapes, a self-organization-based
      synthesis of hollow toroids has, so far, proved to be elusive. Here, we report
      the synthesis of polymer microrings made from rectangular, flat and rigid-core
      monomers with anisotropically predisposed alkene groups, which are crosslinked
      with each other by dithiol linkers using thiol-ene photopolymerization. The
      resulting hollow toroidal structures are shape-persistent and mechanically robust
      in solution. In addition, their size can be tuned by controlling the initial
      monomer concentrations, an observation that is supported by a theoretical
      analysis. These hollow microrings can encapsulate guest molecules in the
      intratoroidal nanospace, and their peripheries can act as templates for circular
      arrays of metal nanoparticles. 

PMID- 24451585
TI  - Biosynthetic consequences of multiple sequential post-transition-state
      bifurcations.
AB  - Selectivity in chemical reactions that form complex molecular architectures from
      simpler precursors is usually rationalized by comparing competing transition
      state structures that lead to different possible products. Herein we describe a
      system for which a single transition-state structure leads to the formation of
      many isomeric products via pathways that feature multiple sequential
      bifurcations. The reaction network described connects the pimar-15-en-8-yl cation
      to miltiradiene, a tricyclic diterpene natural product, and isomers via
      cyclizations and/or rearrangements. The results suggest that the selectivity of
      the reaction is controlled by (post-transition-state) dynamic effects, that is,
      how the carbocation structure changes in response to the distribution of energy
      in its vibrational modes. The inherent dynamical effects revealed herein
      (characterized through quasiclassical direct dynamics calculations using density
      functional theory) have implications not only for the general principles of
      selectivity prediction in systems with complex potential energy surfaces, but
      also for the mechanisms of terpene synthase enzymes and their evolution. These
      findings redefine the challenges faced by nature in controlling the biosynthesis
      of complex natural products. 

PMID- 24451586
TI  - Validation of N-myristoyltransferase as an antimalarial drug target using an
      integrated chemical biology approach.
AB  - Malaria is an infectious disease caused by parasites of the genus Plasmodium,
      which leads to approximately one million deaths per annum worldwide. Chemical
      validation of new antimalarial targets is urgently required in view of rising
      resistance to current drugs. One such putative target is the enzyme N
      myristoyltransferase, which catalyses the attachment of the fatty acid myristate
      to protein substrates (N-myristoylation). Here, we report an integrated chemical
      biology approach to explore protein myristoylation in the major human parasite P.
      falciparum, combining chemical proteomic tools for identification of the
      myristoylated and glycosylphosphatidylinositol-anchored proteome with selective
      small-molecule N-myristoyltransferase inhibitors. We demonstrate that N
      myristoyltransferase is an essential and chemically tractable target in malaria
      parasites both in vitro and in vivo, and show that selective inhibition of N
      myristoylation leads to catastrophic and irreversible failure to assemble the
      inner membrane complex, a critical subcellular organelle in the parasite life
      cycle. Our studies provide the basis for the development of new antimalarials
      targeting N-myristoyltransferase. 

PMID- 24451587
TI  - Conversion of 1-alkenes into 1,4-diols through an auxiliary-mediated formal
      homoallylic C-H oxidation.
AB  - The ubiquitous nature of C-H bonds in organic molecules makes them attractive as
      a target for rapid complexity generation, but brings with it the problem of
      achieving selective reactions. In developing new methodologies for C-H
      functionalization, alkenes are an attractive starting material because of their
      abundance and low cost. Here we describe the conversion of 1-alkenes into 1,4
      diols. The method involves the installation of a new Si,N-type chelating
      auxiliary group on the alkene followed by iridium-catalysed C-H silylation of an
      unactivated delta-C(sp(3))-H bond to produce a silolane intermediate. Oxidation
      of the C-Si bonds affords a 1,4-diol. The method is demonstrated to have broad
      scope and good functional group compatibility by application to the selective 1,4
      oxygenation of several natural products and derivatives. 

PMID- 24451588
TI  - Synthesis of structurally well-defined and liquid-phase-processable graphene
      nanoribbons.
AB  - The properties of graphene nanoribbons (GNRs) make them good candidates for next
      generation electronic materials. Whereas 'top-down' methods, such as the
      lithographical patterning of graphene and the unzipping of carbon nanotubes, give
      mixtures of different GNRs, structurally well-defined GNRs can be made using a
      'bottom-up' organic synthesis approach through solution-mediated or surface
      assisted cyclodehydrogenation reactions. Specifically, non-planar polyphenylene
      precursors were first 'built up' from small molecules, and then 'graphitized' and
      'planarized' to yield GNRs. However, fabrication of processable and
      longitudinally well-extended GNRs has remained a major challenge. Here we report
      a bottom-up solution synthesis of long (>200 nm) liquid-phase-processable GNRs
      with a well-defined structure and a large optical bandgap of 1.88 eV. Self
      assembled monolayers of GNRs can be observed by scanning probe microscopy, and
      non-contact time-resolved terahertz conductivity measurements reveal excellent
      charge-carrier mobility within individual GNRs. Such structurally well-defined
      GNRs may prove useful for fundamental studies of graphene nanostructures, as well
      as the development of GNR-based nanoelectronics. 

PMID- 24451589
TI  - Probing chemical space with alkaloid-inspired libraries.
AB  - Screening of small-molecule libraries is an important aspect of probe and drug
      discovery science. Numerous authors have suggested that bioactive natural
      products are attractive starting points for such libraries because of their
      structural complexity and sp(3)-rich character. Here, we describe the
      construction of a screening library based on representative members of four
      families of biologically active alkaloids (Stemonaceae, the structurally related
      cyclindricine and lepadiformine families, lupin and Amaryllidaceae). In each
      case, scaffolds were based on structures of the naturally occurring compounds or
      a close derivative. Scaffold preparation was pursued following the development of
      appropriate enabling chemical methods. Diversification provided 686 new compounds
      suitable for screening. The libraries thus prepared had structural
      characteristics, including sp(3) content, comparable to a basis set of
      representative natural products and were highly rule-of-five compliant. 

PMID- 24451590
TI  - The rate of the F + H2 reaction at very low temperatures.
AB  - The prototypical F + H2 -> HF + H reaction possesses a substantial energetic
      barrier (~800 K) and might therefore be expected to slow to a negligible rate at
      low temperatures. It is, however, the only source of interstellar HF, which has
      been detected in a wide range of cold (10-100 K) environments. In fact, the
      reaction does take place efficiently at low temperatures due to quantum
      mechanical tunnelling. Rate constant measurements at such temperatures have
      essentially been limited to fast barrierless reactions, such as those between two
      radicals. Using uniform supersonic hydrogen flows we can now report direct
      experimental measurements of the rate of this reaction down to a temperature of
      11 K, in remarkable agreement with state-of-the-art quantum reactive scattering
      calculations. The results will allow a stronger link to be made between
      observations of interstellar HF and the abundance of the most common interstellar
      molecule, H2, and hence a more accurate estimation of the total mass of
      astronomical objects. 

PMID- 24451591
TI  - Ligand-enabled cross-coupling of C(sp3)-H bonds with arylboron reagents via
      Pd(II)/Pd(0) catalysis.
AB  - There have been numerous developments in C-H activation reactions in the past
      decade. Attracted by the ability to functionalize molecules directly at
      ostensibly unreactive C-H bonds, chemists have discovered reaction conditions
      that enable reactions of C(sp(2))-H and C(sp(3))-H bonds with a variety of
      coupling partners. Despite these advances, the development of suitable ligands
      that enable catalytic C(sp(3))-H bond functionalization remains a significant
      challenge. Herein we report the discovery of a mono-N-protected amino acid ligand
      that enables Pd(II)-catalysed coupling of gamma-C(sp(3))-H bonds in triflyl
      protected amines with arylboron reagents. Remarkably, no background reaction was
      observed in the absence of ligand. A variety of amine substrates and arylboron
      reagents were cross-coupled using this method. Arylation of optically active
      substrates derived from amino acids also provides a potential route for preparing
      non-proteinogenic amino acids. 

PMID- 24451592
TI  - Scalable enhancement of graphene oxide properties by thermally driven phase
      transformation.
AB  - Chemical functionalization of graphene is promising for a variety of next
      generation technologies. Although graphene oxide (GO) is a versatile material in
      this direction, its use is limited by the production of metastable, chemically
      inhomogeneous and spatially disordered GO structures under current synthetic
      protocols, which results in poor optoelectronic properties. Here, we present a
      mild thermal annealing procedure, with no chemical treatments involved, to
      manipulate as-synthesized GO on a large scale to enhance sheet properties with
      the oxygen content preserved. Using experiments supported by atomistic
      calculations, we demonstrate that GO structures undergo a phase transformation
      into prominent oxidized and graphitic domains by temperature-driven oxygen
      diffusion. Consequently, as-synthesized GO that absorbs mainly in the ultraviolet
      region becomes strongly absorbing in the visible region, photoluminescence is
      blue shifted and electronic conductivity increases by up to four orders of
      magnitude. Our thermal processing method offers a suitable way to tune and
      enhance the properties of GO, which creates opportunities for various
      applications. 

PMID- 24451593
TI  - Exceptionally fast carbon-carbon bond reductive elimination from gold(III).
AB  - Reductive elimination of carbon-carbon bonds occurs in numerous metal-catalysed
      reactions. This process is well documented for a variety of transition metal
      complexes. However, carbon-carbon bond reductive elimination from a limited
      number of Au(III) complexes has been shown to be a slow and prohibitive process
      that generally requires elevated temperatures. Herein we show that oxidation of a
      series of mono- and bimetallic Au(I) aryl complexes at low temperature generates
      observable Au(III) and Au(II) intermediates. We also show that aryl-aryl bond
      reductive elimination from these oxidized species is not only among the fastest
      observed for any transition metal, but is also mechanistically distinct from
      previously studied alkyl-alkyl and aryl-alkyl reductive eliminations from
      Au(III). 

PMID- 24451594
TI  - Zinc of unsuspected worth.

PMID- 24451595
TI  - International variations in bladder cancer incidence and mortality.
AB  - CONTEXT: Previous studies have reported substantial worldwide regional variations
      in bladder cancer (BCa) incidence and mortality. OBJECTIVE: To describe
      contemporary international variations in BCa incidence and mortality rates and
      trends using the most recent data from the International Agency for Research on
      Cancer (IARC). EVIDENCE ACQUISITION: Estimated 2008 BCa incidence and mortality
      rates for each country by sex were obtained from GLOBOCAN. Recent trends in
      incidence for 43 countries and in mortality for 64 countries were assessed by
      join-point model using data from the IARC's Cancer Incidence in Five Continents
      and from the World Health Organisation's mortality database, respectively.
      EVIDENCE SYNTHESIS: The highest incidence rates for both men and women are found
      in Europe, the United States, and Egypt, and the lowest rates are found in sub
      Saharan Africa, Asia, and South America. Mortality rates are highest in parts of
      Europe and northern Africa and lowest in Asia, Central America, and middle
      Africa. Incidence rates among men decreased in 11 of 43 countries (46 registries)
      (North America, western and northern Europe), remained stable in 20, and
      increased in 12 countries (southern, central, and eastern Europe). Among women,
      incidence rates decreased in 10 countries, stabilised in 22 countries, and
      increased in 12 countries. Mortality rates among men decreased in 32 of 65
      countries (throughout all world regions except Central and South America),
      stabilised in 30 countries, and increased in 3 (Romania, Slovenia, and Cuba).
      Among women, mortality rates decreased in 24 countries, remained stable in 36
      countries, and increased in 5 countries (central and eastern Europe).
      CONCLUSIONS: Incidence and mortality rates in general decreased in most Western
      countries but increased in some eastern European and developing countries. These
      patterns in part may reflect differences in the stage and extent of the tobacco
      epidemic, changes in coding practices, prevalence of schistosomiasis (Africa),
      and occupational exposure.

PMID- 24451605
TI  - Pseudo-Casimir interactions across nematic films with disordered anchoring axis.
AB  - We study the effective pseudo-Casimir interaction forces mediated by a nematic
      liquid-crystalline film bounded by two planar surfaces, one of which imposes a
      random (disordered) distribution of the preferred anchoring axis in the so-called
      easy direction. We consider both the case of a quenched as well as an annealed
      disorder for the easy direction on the disordered surface and analyze the
      resultant fluctuation-induced interaction between the surfaces. In the case of
      quenched disorder, we show that the disorder effects appear additively in the
      total interaction and are dominant at intermediate inter-surface separations.
      Disorder effects are shown to be unimportant at both very small and very large
      separations. In the case of annealed disorder its effects are non-additive in the
      total inter-surface interaction and can be rationalized in terms of a
      renormalized extrapolation length. 

PMID- 24451596
TI  - Hexameric GFP and mCherry reporters for the Drosophila GAL4, Q, and LexA
      transcription systems.
AB  - The ability to distinguish cells and tissues of interest is critical for
      understanding their biological importance. In genetic model organisms, a
      prominent approach for discerning particular cells or tissues from others is the
      use of cell or tissue-specific enhancers to drive fluorescent reporters. This
      approach, however, is often limited by the brightness of the fluorescent
      reporter. To augment the ability to visualize cells or tissues of interest in
      Drosophila melanogaster, homo-hexameric GFP and mCherry reporters were developed
      for the GAL4, Q, and LexA transcription systems and functionally validated in
      vivo. The GFP and mCherry homo-hexameric fusion proteins exhibited significantly
      enhanced fluorescence as compared to monomeric fluorescent reporters and could be
      visualized by direct fluorescence throughout the cytoplasm of neurons, including
      the fine processes of axons and dendrites. These high-sensitivity fluorescent
      reporters of cell morphology can be utilized for a variety of purposes,
      especially facilitating fluorescence-based genetic screens for cell morphology
      phenotypes. These results suggest that the strategy of fusing monomeric
      fluorescent proteins in tandem to enhance brightness should be generalizable to
      other fluorescent proteins and other genetic model organisms. 

PMID- 24451606
TI  - Does affective organizational commitment and experience of meaning at work
      predict long-term sickness absence? An analysis of register-based outcomes using
      pooled data on 61,302 observations in four occupational groups.
AB  - OBJECTIVE: To investigate whether experience of low meaning at work (MAW) and low
      affective organizational commitment (AOC) predicts long-term sickness absence
      (LTSA) for more than 3 consecutive weeks and whether this association is
      dependent on the occupational group. METHODS: Survey data pooling 61,302
      observations were fitted to the DREAM register containing information on payments
      of sickness absence compensation. Using multiadjusted Cox regression,
      observations were followed for an 18-month follow-up period to assess the risk
      for LTSA. RESULTS: Low levels of MAW and AOC significantly increased the risk for
      LTSA during follow-up. Subgroup analyses showed that associations were
      statistically significant for employees working with clients and office workers
      but not for employees working with customers and manual workers. Further analyses
      showed that associations between MAW and LTSA varied significantly across the
      four occupational groups. CONCLUSIONS: Meaning at work and affective
      organizational commitment significantly predict LTSA. Promoting MAW and AOC may
      contribute toward reducing LTSA in contemporary workplaces.

PMID- 24451607
TI  - The predictive validity of the HERO Scorecard in determining future health care
      cost and risk trends.
AB  - OBJECTIVE: To determine the ability of the Health Enhancement Research
      Organization (HERO) Scorecard to predict changes in health care expenditures.
      METHODS: Individual employee health care insurance claims data for 33
      organizations completing the HERO Scorecard from 2009 to 2011 were linked to
      employer responses to the Scorecard. Organizations were dichotomized into "high"
      versus "low" scoring groups and health care cost trends were compared. A
      secondary analysis examined the tool's ability to predict health risk trends.
      RESULTS: "High" scorers experienced significant reductions in inflation-adjusted
      health care costs (averaging an annual trend of -1.6% over 3 years) compared with
      "low" scorers whose cost trend remained stable. The risk analysis was
      inconclusive because of the small number of employers scoring "low." CONCLUSIONS:
      The HERO Scorecard predicts health care cost trends among employers. More
      research is needed to determine how well it predicts health risk trends for
      employees.

PMID- 24451608
TI  - Dietary inflammatory index scores differ by shift work status: NHANES 2005 to
      2010.
AB  - OBJECTIVE: Shift workers are affected by diet- and inflammation-related diseases,
      including cardiovascular disease, diabetes, and cancer. We examined a dietary
      inflammatory index (DII) in relation to shift work from the National Health and
      Nutrition Examination Survey data (2005 to 2010). METHODS: The DII was calculated
      using data from a 24-hour dietary recall. Shift work categories included day
      workers, evening/night shift workers, or rotating shift workers. General linear
      models were fit to examine the relationship between shift work and adjusted mean
      DII values. RESULTS: Among all shift workers and specifically rotating shift
      workers, higher (ie, more pro-inflammatory) mean DII scores (1.01 and 1.07 vs
      0.86; both P <= 0.01) were observed compared with day workers. Women tended to
      express strong evening/night shift effects. CONCLUSIONS: More proinflammatory
      diets observed among shift workers may partially explain increased inflammation
      related chronic disease risk observed in other studies among shift workers
      compared with their day-working counterparts.

PMID- 24451609
TI  - Short-term effects of air pollution on oxygen saturation in a cohort of senior
      adults in Steubenville, Ohio.
AB  - OBJECTIVE: We examine whether ambient air pollution is associated with oxygen
      saturation in 32 elderly subjects in Steubenville, Ohio. METHODS: We used linear
      mixed models to examine the effects of fine particulate matter less than 2.5 MUm
      (PM(2.5)), sulfate (SO(4)(-2)), elemental carbon, and gases on median oxygen
      saturation. RESULTS: An interquartile range increase of 13.4 MUg/m in PM(2.5) on
      the previous day was associated with a decrease of -0.18% (95% confidence
      interval: -0.31 to -0.06) and a 5.1 MUg/m(3) interquartile range increase in
      SO(4)(-2) on the previous day was associated with a decrease of -0.16% (95%
      confidence interval: -0.27 to -0.04) in oxygen saturation during the initial 5
      minute rest period of the protocol. CONCLUSIONS: Increased exposure to air
      pollution, including the nontraffic pollutant SO(4)(-2) from industrial sources,
      led to changes in oxygen saturation that may reflect particle-induced pulmonary
      inflammatory or vascular responses.

PMID- 24451610
TI  - Cognitive disorders and tau-protein expression among retired aluminum smelting
      workers.
AB  - OBJECTIVES: To analyze cognitive functions and tau-protein expression in
      peripheral blood lymphocytes of retired aluminum (Al)-exposed workers. METHODS: A
      total of 66 retired Al potroom workers and 70 unexposed controls were
      investigated. The cognitive functions were assessed with the Mini-Mental State
      Examination. The tau-protein expression in peripheral blood lymphocyte was
      analyzed with Western blot. RESULTS: The cognitive functions of the exposed group
      were significantly decreased. Twelve mild cognitive impairment cases in the
      exposed group and four mild cognitive impairment cases in the control group were
      diagnosed. Significantly higher p-tau181 and p-tau231 levels were detected in the
      Al-exposed workers than in the control group. CONCLUSIONS: The study suggests
      that long-term exposure to Al may cause cognitive disorders and that p-tau181 and
      p-tau231 might be useful indicators for monitoring cognitive decline in Al
      exposed workers.

PMID- 24451611
TI  - Cohort analysis assessing medical and nonmedical cost associated with obesity in
      the workplace.
AB  - OBJECTIVE: Quantify the impact of employee overweight and obesity on costs,
      absence days, and self-reported productivity. METHODS: Employees' retrospective
      body mass index (BMI) values (kg/m(2)) from 2003 to 2011 health appraisal data
      defined three cohorts: BMI < 27, 27 <= BMI < 30, BMI >= 30. Medical, pharmacy,
      sick leave, short-term disability, long-term disability, and workers'
      compensation costs and absence days, and Health Productivity Questionnaire
      responses were compared using regression modeling, controlling for demographics,
      salary, and index year. RESULTS: Among 39,696 (BMI < 27), 14,281 (27 <= BMI <
      30), and 18,801 (BMI >= 30) eligible employees, per-employee adjusted total
      annual costs were $4258, $4873, and $6313, respectively. Medical, pharmacy, sick
      leave, workers' compensation costs and days were higher for higher-BMI cohorts (P
      < 0.01). Employees with BMI >= 30 kg/m(2) had the most short-term disability
      costs and days and least productivity (P < 0.001). CONCLUSIONS: Employees with
      higher BMI levels are associated with significantly more costs and absences and
      lower self-reported productivity.

PMID- 24451612
TI  - A naturopathic approach to the prevention of cardiovascular disease: cost
      effectiveness analysis of a pragmatic multi-worksite randomized clinical trial.
AB  - OBJECTIVE: To determine the cost-effectiveness of a worksite-based naturopathic
      (individualized lifestyle counseling and nutritional medicine) approach to
      primary prevention of cardiovascular disease (CVD). METHODS: Economic evaluation
      alongside a pragmatic, multi-worksite, randomized controlled trial comparing
      enhanced usual care (EUC; usual care plus biometric screening) to the addition of
      a naturopathic approach to CVD prevention (NC+EUC). RESULTS: After 1 year, NC+EUC
      resulted in a net decrease of 3.3 (confidence interval: 1.7 to 4.8) percentage
      points in 10-year CVD event risk (number needed to treat = 30). These risk
      reductions came with average net study-year savings of $1138 in societal costs
      and $1187 in employer costs. There was no change in quality-adjusted life years
      across the study year. CONCLUSIONS: A naturopathic approach to CVD primary
      prevention significantly reduced CVD risk over usual care plus biometric
      screening and reduced costs to society and employers in this multi-worksite-based
      study. Trial Registration clinicaltrials.gov Identifier: NCT00718796.

PMID- 24451614
TI  - Psychometric properties of the 25-item Work Limitations Questionnaire in Japan:
      factor structure, validity, and reliability in information and communication
      technology company employees.
AB  - OBJECTIVE: The 25-item Work Limitations Questionnaire (WLQ-25) measures
      presenteeism but has not been sufficiently validated in a Japanese population.
      METHODS: A total of 451 employees from four information technology companies in
      Tokyo completed the WLQ-25 and questionnaires of other variables on two
      occasions, 2 weeks apart. RESULTS: The WLQ-25 yielded a two-factor structure:
      Cognitive Demand and Physical Demand. These subscales showed good internal
      consistency, and both were associated with adverse working conditions, greater
      perceived job strain, lower skill use, poorer workplace social support, and less
      satisfactory psychological adjustment. Intraclass correlation coefficients of the
      two WLQ-25 subscales between time 1 and time 2 were 0.78 and 0.55, respectively.
      CONCLUSIONS: This study suggests acceptable psychometric properties of the WLQ-25
      in Japan.

PMID- 24451613
TI  - Systemic effects of wood smoke in a short-term experimental exposure study of
      atopic volunteers.
AB  - OBJECTIVE: To investigate whether short-term systemic effects of wood smoke
      occurred in atopic subjects after experimental wood smoke exposures. METHODS: A
      double-blind climate chamber study was conducted on 20 healthy atopic subjects
      with exposures to filtered air and wood smoke. Pneumoproteins, coagulation and
      adhesion factors, and cytokines were measured. Heart rate was monitored with
      pulse monitors. Data were analyzed with mixed models. RESULTS: Few differences in
      the outcomes were observed. Plasma tissue factor remained elevated during
      filtered air exposure (P = 0.002). P-selectin declined independent of exposure (P
      = 0.0006). Interleukin-6 increased after filtered air (P = 0.03). CONCLUSIONS:
      The study confirmed previous observations among nonatopics of limited changes
      after a 3-hour wood smoke exposure.

PMID- 24451615
TI  - Responsiveness of the Work Role Functioning Questionnaire (Spanish version) in a
      general working population.
AB  - OBJECTIVE: To examine the responsiveness of the Work Role Functioning
      Questionnaire (Spanish version) (WRFQ-SpV) so that it could be used in evaluative
      studies. METHODS: A longitudinal survey was performed. Combinations of
      distribution- and anchor-based approaches were used. Five hypotheses were tested,
      examining validity of change scores. The consensus-based standards for the
      selection of health status measurement instruments (COSMIN) guided the study
      design. RESULTS: One hundred two participants (mean age, 47.3 years; SD = 10.3
      years) completed the WRFQ-SpV twice, within a mean interval of 3.7 (SD = 1.8)
      months. Four hypotheses were confirmed and one was rejected. It was verified that
      the WRFQ-SpV was able to detect (true) changes over time. CONCLUSION: Suggestive
      evidence about the possible use of the WRFQ-SpV with evaluative purposes was
      provided. More research is needed to examine the instrument responsiveness for
      groups whose health is stable or deteriorates.

PMID- 24451616
TI  - Implications of lumbar epidural steroid injections after lumbar surgery.
AB  - OBJECTIVE: Assess the relationship between performing lumbar epidural steroid
      injections (ESIs) after lumbar surgery and workers' compensation claim duration
      and cost. METHODS: A multivariate logistic regression was used to determine the
      association between performing ESI after the first lumbar surgery in 11,394 lost
      time injury claims filed from 1999 to 2002 followed for 7 years postinjury.
      RESULTS: Odds ratio of costs more than $100,000 is 6.49 (95% confidence interval:
      4.30 to 9.81) for ever having lumbar ESI after the first lumbar surgery, compared
      with no spinal procedures, controlling for sex, age, attorney involvement, opioid
      use, other spinal procedures, and claim duration. Odds ratio of having claim
      duration longer than 1000 days was 14.73 (95% confidence interval: 7.01 to
      30.95). CONCLUSION: Lumbar ESI after the first lumbar surgery was associated with
      high cost and longer claim duration.

PMID- 24451617
TI  - Is carpal tunnel syndrome related to computer exposure at work? A review and meta
      analysis.
AB  - OBJECTIVE: A meta-analysis on epidemiological studies was undertaken to assess
      association between carpal tunnel syndrome (CTS) and computer work. METHODS: Four
      databases (PubMed, Embase, Web of Science, and Base de Donnees de Sante Publique)
      were searched with cross-references from published reviews. We included recent
      studies, original epidemiological studies for which the association was assessed
      with blind reviewing with control group. Relevant associations were extracted,
      and a metarisk was calculated using the generic variance approach (meta-odds
      ratio [meta-OR]). RESULTS: Six studies met the criteria for inclusion. Results
      are contradictory because of heterogeneous work exposure. The meta-OR for
      computer use was 1.67 (95% confidence interval [CI], 0.79 to 3.55). The meta-OR
      for keyboarding was 1.11 (95% CI, 0.62 to 1.98) and for mouse 1.94 (95% CI, 0.90
      to 4.21). CONCLUSION: It was not possible to show an association between computer
      use and CTS, although some particular work circumstances may be associated with
      CTS.

PMID- 24451618
TI  - Collaboration between general practitioners and occupational physicians: a
      comparison of the results of two national surveys in France.
AB  - OBJECTIVE: To study the perceptions that general practitioners (GPs) and
      occupational physicians (OPs) have of GPs' role in occupational health and their
      willingness to work together to prevent the exclusion of patients with
      disabilities from the workplace. METHODS: Cross-sectional telephone survey of two
      randomly selected national samples of GPs and OPs was conducted. RESULTS: The
      majority of GPs and OPs are in favor of cooperation, especially to prevent
      exclusion from the workplace. However, some GPs lack trust in OPs' independence,
      an attitude associated negatively with the practice of GP referral to OPs to
      anticipate disability-related problems likely to occur when returning to work
      after a prolonged sick leave. CONCLUSIONS: There are some barriers to
      cooperation, on the part of both OPs and GPs. Initiatives are needed to encourage
      cooperation between these two types of physicians.

PMID- 24451619
TI  - Revisiting ventilatory and cardiovascular predictions of whole-body metabolic
      rate.
AB  - OBJECTIVE: The influence of variations in exercise mode, thermal state, and load
      carriage on cardiac and ventilatory predictors of metabolic rate were
      investigated. METHODS: Fifteen males were studied at rest and during whole-,
      upper-, and lower-body exercise (unloaded and loaded) under thermoneutral and hot
      conditions. RESULTS: Ventilatory predictions were superior in thermoneutral
      (residual mean square error range: 0.04 to 0.17 L.min(-1) vs 0.21 to 0.36 L.min(
      1)) and hot conditions (0.03 to 0.07 L.min(-1) vs 0.21 to 0.24 L.min(-1)).
      Predictions derived from whole- or lower-body exercise, and unloaded or loaded
      exercise could be interchanged without significant error. Nevertheless, a mode
      specific prediction was required for upper-body work, and mild hyperthermia
      significantly reduced the precision of cardiac predictions. CONCLUSION:
      Ventilatory predictions were more precise, but errors from heart-rate predictions
      could be minimized by using thermal-state and exercise mode-specific predictions.

PMID- 24451620
TI  - A new method for maturity-dependent fractionation of neutrophil progenitors
      applicable for the study of myelodysplastic syndromes.
AB  - We applied our new method, maturity-dependent fractionation of bone marrow
      derived neutrophil progenitors, to a study of gene expression profiles during
      granulopoiesis in myelodysplastic syndromes. CD34+ cells with low density [F1],
      CD11b-/CD16- [F2], CD11b+/CD16- [F3] and CD11b+/CD16low [F4] with intermediate
      density, CD11b+/CD16int [F5] and CD11b+/CD16high [F6] with high density were
      isolated from six patients. Although AML1 and C/EBP-epsilon mRNA peaked at F1 and
      F4, respectively, in healthy individuals, C/EBP-epsilon was maximized at F2/F3 in
      all patients, two of whom showed simultaneous peaks of AML1 at F2. Thus, this
      fractionation is useful to detect mistimed induction of granulopoiesis-regulating
      genes in myelodysplastic syndromes. 

PMID- 24451621
TI  - jmodeltest.org: selection of nucleotide substitution models on the cloud.
AB  - The selection of models of nucleotide substitution is one of the major steps of
      modern phylogenetic analysis. Different tools exist to accomplish this task,
      among which jModelTest 2 (jMT2) is one of the most popular. Still, to deal with
      large DNA alignments with hundreds or thousands of loci, users of jMT2 need to
      have access to High Performance Computing clusters, including installation and
      configuration capabilities, conditions not always met. Here we present
      jmodeltest.org, a novel web server for the transparent execution of jMT2 across
      different platforms and for a wide range of users. Its main benefit is
      straightforward execution, avoiding any configuration/execution issues, and
      reducing significantly in most cases the time required to complete the analysis.

PMID- 24451622
TI  - Reference-free cell mixture adjustments in analysis of DNA methylation data.
AB  - MOTIVATION: Recently there has been increasing interest in the effects of cell
      mixture on the measurement of DNA methylation, specifically the extent to which
      small perturbations in cell mixture proportions can register as changes in DNA
      methylation. A recently published set of statistical methods exploits this
      association to infer changes in cell mixture proportions, and these methods are
      presently being applied to adjust for cell mixture effect in the context of
      epigenome-wide association studies. However, these adjustments require the
      existence of reference datasets, which may be laborious or expensive to collect.
      For some tissues such as placenta, saliva, adipose or tumor tissue, the relevant
      underlying cell types may not be known. RESULTS: We propose a method for
      conducting epigenome-wide association studies analysis when a reference dataset
      is unavailable, including a bootstrap method for estimating standard errors. We
      demonstrate via simulation study and several real data analyses that our proposed
      method can perform as well as or better than methods that make explicit use of
      reference datasets. In particular, it may adjust for detailed cell type
      differences that may be unavailable even in existing reference datasets.
      AVAILABILITY AND IMPLEMENTATION: Software is available in the R package
      RefFreeEWAS. Data for three of four examples were obtained from Gene Expression
      Omnibus (GEO), accession numbers GSE37008, GSE42861 and GSE30601, while reference
      data were obtained from GEO accession number GSE39981. CONTACT:
      andres.houseman@oregonstate.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 24451623
TI  - RAxML version 8: a tool for phylogenetic analysis and post-analysis of large
      phylogenies.
AB  - MOTIVATION: Phylogenies are increasingly used in all fields of medical and
      biological research. Moreover, because of the next-generation sequencing
      revolution, datasets used for conducting phylogenetic analyses grow at an
      unprecedented pace. RAxML (Randomized Axelerated Maximum Likelihood) is a popular
      program for phylogenetic analyses of large datasets under maximum likelihood.
      Since the last RAxML paper in 2006, it has been continuously maintained and
      extended to accommodate the increasingly growing input datasets and to serve the
      needs of the user community. RESULTS: I present some of the most notable new
      features and extensions of RAxML, such as a substantial extension of substitution
      models and supported data types, the introduction of SSE3, AVX and AVX2 vector
      intrinsics, techniques for reducing the memory requirements of the code and a
      plethora of operations for conducting post-analyses on sets of trees. In
      addition, an up-to-date 50-page user manual covering all new RAxML options is
      available.

PMID- 24451624
TI  - CAFE: an R package for the detection of gross chromosomal abnormalities from gene
      expression microarray data.
AB  - SUMMARY: The current methods available to detect chromosomal abnormalities from
      DNA microarray expression data are cumbersome and inflexible. CAFE has been
      developed to alleviate these issues. It is implemented as an R package that
      analyzes Affymetrix *.CEL files and comes with flexible plotting functions,
      easing visualization of chromosomal abnormalities. AVAILABILITY AND
      IMPLEMENTATION: CAFE is available from https://bitbucket.org/cob87icW6z/cafe/ as
      both source and compiled packages for Linux and Windows. It is released under the
      GPL version 3 license. CAFE will also be freely available from Bioconductor.
      CONTACT: sander.h.bollen@gmail.com or nancy.mah@mdc-berlin.de SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 24451625
TI  - MEMBPLUGIN: studying membrane complexity in VMD.
AB  - SUMMARY: Computer simulations are giving way to more complex and accurate studies
      of biological membranes by molecular dynamics (MD) simulations. The analysis of
      MD trajectories comprises the biophysical characterization of membrane properties
      or the study of protein-lipid interactions and dynamics. However, there is a lack
      of automated tools to analyse MD simulations of complex membrane or membrane
      protein systems. Here we present MEMBPLUGIN, a plugin for the Visual Molecular
      Dynamics package that provides algorithms to measure a host of essential
      biophysical properties in simulated membranes. MEMBPLUGIN features are accessible
      both through a user-friendly graphical interface and as command-line procedures
      to be invoked in analysis scripts. AVAILABILITY AND IMPLEMENTATION: MEMBPLUGIN is
      a VMD extension written in Tcl. Multi-platform source code, documentation and
      tutorials are freely available at http://membplugin.sourceforge.net. CONTACT:
      toni.giorgino@isib.cnr.it or jana.selent@upf.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 24451626
TI  - InterProScan 5: genome-scale protein function classification.
AB  - MOTIVATION: Robust large-scale sequence analysis is a major challenge in modern
      genomic science, where biologists are frequently trying to characterize many
      millions of sequences. Here, we describe a new Java-based architecture for the
      widely used protein function prediction software package InterProScan.
      Developments include improvements and additions to the outputs of the software
      and the complete reimplementation of the software framework, resulting in a
      flexible and stable system that is able to use both multiprocessor machines
      and/or conventional clusters to achieve scalable distributed data analysis.
      InterProScan is freely available for download from the EMBl-EBI FTP site and the
      open source code is hosted at Google Code.

PMID- 24451627
TI  - IQRray, a new method for Affymetrix microarray quality control, and the
      homologous organ conservation score, a new benchmark method for quality control
      metrics.
AB  - MOTIVATION: Microarray results accumulated in public repositories are widely
      reused in meta-analytical studies and secondary databases. The quality of the
      data obtained with this technology varies from experiment to experiment, and an
      efficient method for quality assessment is necessary to ensure their reliability.
      RESULTS: The lack of a good benchmark has hampered evaluation of existing methods
      for quality control. In this study, we propose a new independent quality metric
      that is based on evolutionary conservation of expression profiles. We show, using
      11 large organ-specific datasets, that IQRray, a new quality metrics developed by
      us, exhibits the highest correlation with this reference metric, among 14 metrics
      tested. IQRray outperforms other methods in identification of poor quality arrays
      in datasets composed of arrays from many independent experiments. In contrast,
      the performance of methods designed for detecting outliers in a single experiment
      like Normalized Unscaled Standard Error and Relative Log Expression was low
      because of the inability of these methods to detect datasets containing only low
      quality arrays and because the scores cannot be directly compared between
      experiments. AVAILABILITY AND IMPLEMENTATION: The R implementation of IQRray is
      available at: ftp://lausanne.isb-sib.ch/pub/databases/Bgee/general/IQRray.R.
      CONTACT: Marta.Rosikiewicz@unil.ch SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 24451628
TI  - BLESS: bloom filter-based error correction solution for high-throughput
      sequencing reads.
AB  - MOTIVATION: Rapid advances in next-generation sequencing (NGS) technology have
      led to exponential increase in the amount of genomic information. However, NGS
      reads contain far more errors than data from traditional sequencing methods, and
      downstream genomic analysis results can be improved by correcting the errors.
      Unfortunately, all the previous error correction methods required a large amount
      of memory, making it unsuitable to process reads from large genomes with
      commodity computers. RESULTS: We present a novel algorithm that produces accurate
      correction results with much less memory compared with previous solutions. The
      algorithm, named BLoom-filter-based Error correction Solution for high-throughput
      Sequencing reads (BLESS), uses a single minimum-sized Bloom filter, and is also
      able to tolerate a higher false-positive rate, thus allowing us to correct errors
      with a 40* memory usage reduction on average compared with previous methods.
      Meanwhile, BLESS can extend reads like DNA assemblers to correct errors at the
      end of reads. Evaluations using real and simulated reads showed that BLESS could
      generate more accurate results than existing solutions. After errors were
      corrected using BLESS, 69% of initially unaligned reads could be aligned
      correctly. Additionally, de novo assembly results became 50% longer with 66%
      fewer assembly errors. AVAILABILITY AND IMPLEMENTATION: Freely available at
      http://sourceforge.net/p/bless-ec CONTACT: dchen@illinois.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 24451629
TI  - h5vc: scalable nucleotide tallies with HDF5.
AB  - SUMMARY: As applications of genome sequencing, including exomes and whole
      genomes, are expanding, there is a need for analysis tools that are scalable to
      large sets of samples and/or ultra-deep coverage. Many current tool chains are
      based on the widely used file formats BAM and VCF or VCF-derivatives. However,
      for some desirable analyses, data management with these formats creates
      substantial implementation overhead, and much time is spent parsing files and
      collating data. We observe that a tally data structure, i.e. the table of counts
      of nucleotides * samples * strands * genomic positions, provides a reasonable
      intermediate level of abstraction for many genomics analyses, including single
      nucleotide variant (SNV) and InDel calling, copy-number estimation and mutation
      spectrum analysis. Here we present h5vc, a data structure and associated software
      for managing tallies. The software contains functionality for creating tallies
      from BAM files, flexible and scalable data visualization, data quality
      assessment, computing statistics relevant to variant calling and other
      applications. Through the simplicity of its API, we envision making low-level
      analysis of large sets of genome sequencing data accessible to a wider range of
      researchers. AVAILABILITY AND IMPLEMENTATION: The package H5VC for the
      statistical environment R is available through the Bioconductor project. The HDF5
      system is used as the core of our implementation. CONTACT: pyl@embl.de or
      whuber@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 24451630
TI  - The bidirectional relationship between pain intensity and sleep
      disturbance/quality in patients with low back pain.
AB  - OBJECTIVES: This study investigated the bidirectional relationship between the
      intensity of low back pain (LBP) and sleep disturbance. Further, the study aimed
      to determine whether any relationship is dependent on pain duration, symptoms of
      depression and anxiety, and the method of sleep assessment (subjective vs.
      objective). MATERIALS AND METHODS: Eighty patients with LBP completed a sleep
      diary. A subgroup of 50 patients additionally wore an electronic device (Armband)
      to measure sleep for 7 consecutive days. Pain intensity was assessed twice daily
      using a sleep diary. Depression and anxiety symptoms were assessed at baseline
      using the Depression Anxiety Stress Scale questionnaire. Generalized estimating
      equations (GEE) with an exchangeable correlation structure were used to examine
      the relationship between day-time pain intensity and sleep. RESULTS: The GEE
      analysis showed that a night of poor sleep quality, difficulty falling sleep
      (assessed by the sleep diary), waking after sleep onset, and low sleep efficiency
      (assessed by the sleep diary and Armband) were followed by a day with higher pain
      intensity. Further, a day with higher pain intensity was associated with a
      decrease in the subsequent night's sleep quality, an increase in sleep latency
      (assessed by the sleep diary), waking after sleep onset (assessed by both
      measures), and low sleep efficiency (assessed by the Armband). DISCUSSION: The
      findings demonstrate that there is a bidirectional relationship between sleep and
      pain intensity in patients with LBP. The relationship is independent of pain
      duration and baseline symptoms of depression and anxiety and somewhat dependent
      on the method of sleep measurement (sleep diary or Armband). Future research is
      needed to determine whether targeting sleep improvement in patients with LBP
      contributes to pain reduction.

PMID- 24451631
TI  - MiR-203 involves in neuropathic pain development and represses Rap1a expression
      in nerve growth factor differentiated neuronal PC12 cells.
AB  - OBJECTIVES: Although microRNAs (miRNAs) have been shown to play a role in
      numerous biological processes, their function in neuropathic pain is not clear.
      The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an
      established model of neuropathic pain, so we examined miRNA expression and
      function in the spinal dorsal horn in bCCI rats. METHODS: Microarray and real
      time polymerase chain reaction were used to examine the expression of miRNA in
      nerve system of bCCI rats, and the targets of miRNA were predicted by
      bioinformatic approaches. The function of specific miRNA was estimated through
      the methods of gene engineering. RESULTS: This study revealed substantially (~10
      fold) decreased miR-203 expression in the spinal dorsal horns but not the dorsal
      root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a
      protein expression was upregulated in bCCI rat spinal dorsal horns. We further
      verified that miR-203 directly targeted the 3'-untranslated region of the rap1a
      gene, thereby decreasing rap1a protein expression in neuron-like cells.
      DISCUSSION: Rap1a has diverse neuronal functions and their perturbation is
      responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved
      in peripheral sensitization. These data suggest a potential role for miR-203 in
      regulating neuropathic pain development, and Rap1a is a validated target gene in
      vitro. Results from our study and others indicate the possibility that Rap1a may
      be involved in pain. We hope that these results can provide support for future
      research into miR-203 in gene therapy for neuropathic pain.

PMID- 24451632
TI  - You may need a nerve to treat pain: the neurobiological rationale for vagal nerve
      activation in pain management.
AB  - OBJECTIVES: Pain is a complex common health problem, with important implications
      for quality of life and with huge economic consequences. Pain can be elicited due
      to tissue damage, as well as other multiple factors such as inflammation and
      oxidative stress. Can there be 1 therapeutic pathway that may target multiple
      etiologic factors in pain? METHODS: In the present article, we review evidence
      for the relationships between vagal nerve activity and pain, and between vagal
      nerve activity and 5 factors that are etiologic to or protective in pain.
      RESULTS: Vagal nerve activity inhibits inflammation, oxidative stress, and
      sympathetic activity, activates brain regions that can oppose the brain "pain
      matrix," and finally it might influence the analgesic effects of opioids.
      Together, these can explain the antinociceptive effects of vagal nerve activation
      or of acetylcholine, the principal vagal nerve neurotransmitter. These findings
      form an evidence-based neurobiological rationale for testing and possibly
      implementing different vagal nerve-activating treatments in pain conditions.
      DISCUSSION: In this article, we show evidence for the relationships between vagal
      nerve activity and pain, and between vagal nerve activity and 5 factors that are
      etiologic to pain. Given the evidence and effects of the vagus nerve activation
      in pain, people involved in pain therapy may need to seriously consider
      activation of this nerve.

PMID- 24451633
TI  - Approaches to Scaffold Hopping.

PMID- 24451634
TI  - De novo design - hop(p)ing against hope.
AB  - Current trends in computational de novo design provide a fresh approach to
      'scaffold-hopping' in drug discovery. The methodological repertoire is no longer
      limited to receptor-based methods, but specifically ligand-based techniques that
      consider multiple properties in parallel, including the synthetic feasibility of
      the computer-generated molecules and their polypharmacology, provide innovative
      ideas for the discovery of new chemical entities. The concept of fragment-based
      and virtual reaction-driven design enables rapid compound optimization from
      scratch with a manageable complexity of the search. Starting from known drugs as
      a reference, such algorithms suggest drug-like molecules with motivated scaffold
      variations, and advanced mathematical models of structure-activity landscapes and
      multi-objective design techniques have created new opportunities for hit and lead
      finding.

PMID- 24451635
TI  - Building in molecular diversity for targeted libraries.
AB  - The use of gene-focussed libraries for screening against protein targets can
      improve timelines for drug discovery projects. This is especially true when the
      library is based on a novel core scaffold, avoiding the potential need to
      scaffold hop from early hits. Identification of an appropriate novel scaffold is
      therefore integral to the success of such a library. In this article we outline a
      new method to aid scaffold design that combines structure- based virtual
      screening (VS) with a second phase in which fragmentation of the output is made
      before the final scaffold design step. Through consideration of a refined set of
      bound fragments, in the context of the compounds from which they originated,
      appropriate vectors for appended R-groups can be assigned before validation of
      the final library.

PMID- 24451636
TI  - De-peptidising protein-protein interactions - big jobs for small molecules.
AB  - Virtually all biological processes rely on protein-protein interactions (PPIs)
      for signal propagation, therefore representing a vast array of potentially viable
      therapeutic intervention points. Targeting PPIs is a relatively novel drug
      development strategy so computational approaches towards analysing the interface
      between protein partners and predicting the likelihood of developing a small
      molecule inhibitor are still progressing. This review provides an overview of
      recent successful examples of computational methodologies used to predict
      druggable PPIs and small molecules designed to inhibit them.

PMID- 24451637
TI  - Molecular topology - dissimilar similarities.
AB  - The present paper depicts the role of molecular topology in the study of
      similarity-dissimilarity between molecular structures. It proves that molecular
      topology represents a very useful tool for getting common patterns of
      pharmacological activity and hence an efficient approach for the search of novel
      lead drugs.

PMID- 24451638
TI  - Scaffold variations in amine warhead of histamine H3 receptor antagonists.
AB  - The histamine H3 receptor (H3R) is involved in numerous regulatory
      neurotransmission processes and there-fore, is a prominent target for centrally
      occurring disease with some promising clinical candidates. Previous research
      resulted in the identification of a core pharmacophore blueprint for H3R
      antagonists/inverse agonists, which when inserted in a molecule, mostly ensures
      acceptable affinity. Nevertheless, variations of scaffold and peripheral areas
      can increase potency and pharmacokinetic profile of drug candidates. The
      variations in amine scaffolds of antagonists for this aminergic GPCR are of
      special importance.

PMID- 24451639
TI  - Molecular crime scene investigation - dusting for fingerprints.
AB  - In chemoinformatics and drug design, fingerprints (FPs) are defined as string
      representations of molecular structure and properties and are popular descriptors
      for similarity searching. FPs are generally characterized by the simplicity of
      their design and ease of use. Despite a long history in chemoinformatics, the
      potential and limitations of FP searching are often not well under- stood.
      Standard FPs can also be subjected to engineering techniques to tune them for
      specific search applications.

PMID- 24451640
TI  - Small-molecule modulation of protein-protein interactions.

PMID- 24451641
TI  - Probing structural adaptivity at PPI interfaces with small molecules.
AB  - There is strong interest in developing small molecules that modulate protein
      protein interactions (PPI), since such compounds could serve as drug leads or as
      probes of protein function. Fragment-based ligand discovery has been a
      particularly useful approach for modulating PPI. Fragments are typically <250 Da
      compounds that bind to proteins with weak affinity but high ligand efficiency.
      Here, we review a method for fragment- based ligand discovery using covalent
      disulfide trapping (Tethering). Tethering uses a native or engineered cysteine
      residue to select thiol-containing fragments that bind to the protein near the
      tethering cysteine. Taking advantage of the site-directed nature of Tethering,
      one can investigate the 'druggability' of particular binding sites on a protein
      surface; furthermore, Tethering has been used to find new binding sites and to
      stabilize allosteric conformations. We review the principles of Tethering and
      discuss two examples where disulfide trapping has expanded our understanding of
      PPI. For the cytokine interleukin-2 (IL2), Tethering identified a binding site
      adjacent to the IL2/IL2- receptor and a new site allosterically coupled to this
      PPI. For the kinase PDK1, Tethering identified ligands that activated or
      inhibited enzymatic activity by bind-ing to a single allosteric site. These
      examples provide a context for successful fragment-discovery projects, in which
      complementary technologies work together to identify starting points for chemical
      biology and drug discovery.

PMID- 24451642
TI  - Inhibitors of protein-protein interactions: new methodologies to tackle this
      challenge.
AB  - Several advances in the fields of crystallography, molecular modeling,
      biophysical assays and chemistry are converging to making protein-protein
      interaction targets more amenable to drug design. These include steps towards
      improving crystallization of protein-protein complexes, identifying the clusters
      of residues that constitute putative small molecule binding 'hot spots',
      generating new methods for detecting the binding of small molecules to target
      proteins, and generating custom libraries via diversity oriented synthesis to
      enable the identification of natural-product-like hits.

PMID- 24451643
TI  - Rational design of LEDGINs as first allosteric integrase inhibitors for the
      treatment of HIV infection.
AB  - The interaction between lens epithelium-derived growth factor (LEDGF/p75) and HIV
      1 integrase (IN) is an attractive target for antiviral development because its
      inhibition blocks HIV replication. Developing novel small molecules that disrupt
      the LEDGF/p75-IN interaction constitutes a promising new therapeutic strategy for
      the treatment of HIV. Here we will highlight recent advances in the design and
      development of small-molecule inhibitors binding to the LEDGF/p75 binding pocket
      of IN, referred to as LEDGINs.

PMID- 24451645
TI  - Inhibition of PDZ domain-mediated interactions.
AB  - Modulating protein-protein interactions constitutes a promising strategy both for
      the investigation of biological mechanisms and for developing new therapeutic
      approaches. Among the many types of inter-actions, PDZ domain-mediated
      interactions (PDMIs) have emerged over the last decade as attractive targets in
      the drug discovery field. Indeed, these small domains are involved in the
      regulation of many signaling pathways and possess structural properties which are
      favorable for the design of competing ligands. Herein, we describe the recent
      approaches developed to inhibit this class of protein-protein interactions.

PMID- 24451644
TI  - Small molecule inhibitors of the HIV-1 virulence factor, Nef.
AB  - Although antiretroviral therapy has revolutionized the clinical management of
      AIDS, life-long treatment is required because these drugs do not eradicate HIV-
      infected cells. Chronic antiretroviral therapy may not protect AIDS patients from
      cognitive impairment, raising important quality of life issues. Because of the
      rise of HIV strains resistant to current drugs and uncertain vaccine prospects,
      an urgent need exists for the discovery and development of new therapeutic
      approaches. This review is focused on one such approach, which involves targeting
      HIV-1 Nef, a viral accessory protein essential for AIDS pathogenesis.

PMID- 24451646
TI  - Small molecules modulation of 14-3-3 protein-protein interactions.
AB  - 14-3-3 is a family of highly conserved regulatory proteins which is attracting a
      significant interest due to its potential role as target for pharmacological
      intervention against cancer and neurodegenerative disorders. Although modulating
      protein-protein interactions (PPI) is still conceived as a challenging task in
      drug discovery, in past few years peptide inhibitors and small molecular
      modulators of 14-3-3 PPI have been described. Here we examine structural and
      biological features of 14-3-3 and propose an overview on techniques used for
      discovering small molecular inhibitors and stabilizers of 14-3-3 PPI.

PMID- 24451647
TI  - Clinicopathological features of mucoepidermoid carcinoma.
AB  - OBJECTIVE: We aimed to examine the clinical usefulness of a new World Health
      Organization classification scheme for salivary gland mucoepidermoid carcinoma,
      and to identify the factors most strongly associated with prognosis and outcome.
      METHODS: The clinicopathological features of 45 patients who received treatment
      for mucoepidermoid carcinoma between 1986 and 2010 were retrospectively
      investigated. RESULTS: The overall disease-specific 5-year survival rate was 81.8
      per cent. The rate for patients with low-grade tumours (92.5 per cent) was
      significantly higher than that for patients with intermediate or high-grade
      tumours (52.2 per cent). Univariate analysis revealed that five factors were
      significantly associated with five-year survival: age, tumour stage
      classification, lymph node status, histological grade and treatment method. Four
      factors were significant in multivariate analysis: age, sex, tumour stage
      classification and lymph node status. CONCLUSION: The new World Health
      Organization classification was useful in predicting disease progression in
      patients with mucoepidermoid carcinoma. Patients with high-grade tumours or other
      prognostic factors positively associated with disease progression should be
      carefully evaluated and monitored.

PMID- 24451648
TI  - PARK2/Parkin-mediated mitochondrial clearance contributes to proteasome
      activation during slow-twitch muscle atrophy via NFE2L1 nuclear translocation.
AB  - Skeletal muscle atrophy is thought to result from hyperactivation of
      intracellular protein degradation pathways, including autophagy and the ubiquitin
      proteasome system. However, the precise contributions of these pathways to muscle
      atrophy are unclear. Here, we show that an autophagy deficiency in denervated
      slow-twitch soleus muscles delayed skeletal muscle atrophy, reduced mitochondrial
      activity, and induced oxidative stress and accumulation of PARK2/Parkin, which
      participates in mitochondrial quality control (PARK2-mediated mitophagy), in
      mitochondria. Soleus muscles from denervated Park2 knockout mice also showed
      resistance to denervation, reduced mitochondrial activities, and increased
      oxidative stress. In both autophagy-deficient and Park2-deficient soleus muscles,
      denervation caused the accumulation of polyubiquitinated proteins. Denervation
      induced proteasomal activation via NFE2L1 nuclear translocation in control mice,
      whereas it had little effect in autophagy-deficient and Park2-deficient mice.
      These results suggest that PARK2-mediated mitophagy plays an essential role in
      the activation of proteasomes during denervation atrophy in slow-twitch muscles. 

PMID- 24451650
TI  - Rivaroxaban in clinical practice for atrial fibrillation with special reference
      to prothrombin time.
AB  - BACKGROUND:  Prothrombin time (PT) distribution in Japanese nonvalvular atrial
      fibrillation (NVAF) patients under rivaroxaban therapy remains to be clarified.
      METHODS AND RESULTS:  Between May 2012 and July 2013, 115 NVAF patients received
      rivaroxaban (PT was measured in 94; reagent: recombiplastin). In these patients,
      (1) PT values were distributed widely from patient to patient and from peak to
      trough, (2) the time-dependence was obscure with sampling at any time in the
      outpatient clinic, and (3) the incidence of adverse events was too low for
      analyzing the relation with PT. CONCLUSIONS:  We report the distribution of PT
      for Japanese NVAF patients under rivaroxaban therapy in real-world clinical
      practice.  

PMID- 24451649
TI  - Emergency care of acute myocardial infarction and the great East Japan earthquake
      disaster.
AB  - BACKGROUND: Although emergency care of acute myocardial infarction (AMI) could
      theoretically be improved through improved patient delay, this notion remains to
      be confirmed. Additionally, the influence of large earthquakes on the emergency
      care of AMI cases remains to be elucidated. The Great East Japan Earthquake
      (March 11, 2011) has enabled us to address these issues. METHODS AND RESULTS:  We
      analyzed the data from 2008 to 2011 (n=3,937) in the Miyagi AMI Registry Study.
      In-hospital mortality was significantly lower in 2011 as compared with the
      previous 3 years (7.3% vs. 10.5%, P<0.05). This improvement was noted especially
      during the first 2 months after the Earthquake, associated with shorter elapsing
      time from onset to admission (120 vs. 240min, P<0.001) and higher performance
      rate of primary percutaneous coronary intervention (PCI) (86.8% vs. 76.2%,
      P<0.01). Importantly, after the Earthquake, patients with early admission (<=3h
      from onset) was significantly increased (59.1% vs. 47.0%, P<0.05) and their
      prognosis became better (7.9% vs. 11.4%, P=0.02), associated with a lower
      prevalence of heart failure on admission (6.9% vs. 16.2%, P=0.02) and higher
      performance rate of primary PCI (89.1% vs. 76.4%, P<0.01). CONCLUSIONS: 
      Emergency care of AMI improved soon after the Great East Japan Earthquake
      compared with ordinary times by the contribution of earlier admission from onset
      and higher performance rate of primary PCI.  (Circ J 2014; 78: 634-643).

PMID- 24451651
TI  - Challenges in long-term mechanical circulatory support and biological replacement
      of the failing heart.
AB  - The burden of advanced heart failure is reaching epidemic proportions. Generally
      considered for cardiac transplantation, patients often cannot receive this
      therapy because of their advanced age, comorbidity or the scarcity of donors.
      Most transplants are concentrated in North America and Europe, with the average
      center performing fewer than 20 annual transplants. A search for nonbiological
      means of cardiac support has led to the advent of mechanical circulatory support
      (MCS), a concept now entrenched as a bridge to transplantation or, for those
      ineligible for transplantation, as lifetime therapy. In this review we discuss
      contemporary challenges posed by the changing epidemiology of cardiac transplant
      and MCS and outline the basis for an understanding of the future of this
      important therapeutic stance.  

PMID- 24451652
TI  - Hard rods in a cylindrical pore: the nematic-to-smectic phase transition.
AB  - The effect of cylindrical confinement on the phase behaviour of a system of
      parallel hard rods is studied using Onsager's second-virial theory. The hard rods
      are represented as hard cylinders of diameter D and length L, while the
      cylindrical pore is infinite with diameter W. The interaction between the wall
      and the rods is hard repulsive, and it is assumed that molecules are parallel to
      the surface of the pore (planar anchoring). In very narrow pores (D < W < 2D),
      the structure is homogeneous and the system behaves as a one-dimensional Tonks
      gas. For wider pores, inhomogeneous fluid structures emerge because of the
      lowering of the average excluded volume due to the wall-particle interaction. The
      bulk nematic-smectic A phase transition is replaced by a transition between
      inhomogeneous nematic and smectic A phases. The smectic is destabilized with
      respect to the nematic for decreasing pore width; this effect becomes substantial
      for W < 10D. For W > 100D, results for bulk and confined fluids agree well due to
      the short range effect of the wall (~ 3-4D).

PMID- 24451654
TI  - Continuing improvement in type 2 diabetes care through performance-based
      evaluations.
AB  - AIMS: The timely evidence-based care of type 2 diabetes mellitus (T2DM) is
      imperative for achieving and maintaining glycemic control, reducing
      complications, and changing the paradigm of this epidemic. Based largely on
      results from earlier performance improvement (PI) activities, we conducted a
      continuing medical education (CME)-certified PI activity to foster improved
      adherence to guideline recommendations and current evidence for the care of
      patients with T2DM. METHODS: Participants engaged in a 3-stage process of self
      assessment, goal setting, and reassessment. RESULTS: A total of 64 clinicians
      completed the entire PI process, abstracting data from 1600 patient charts before
      and after a period of self-improvement. After the intervention, clinicians were
      more likely to assess patients for disease-related complications and provide
      counseling on proper nutrition, exercise, and smoking cessation. Patients with
      A1C, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) values
      above goal (defined as A1C >=7, BP >=130/80 mm Hg, and LDL-C >100 g/dL) were more
      likely to receive treatment modifications compared with baseline clinician
      performance. Significant changes observed in patient outcomes included improved
      mean A1C values (baseline 7.5% vs postintervention 7.3%; P = .027), decreased
      likelihood of BP at or above 130/80 mm Hg (baseline 37% vs postintervention 30%;
      P < .001), and decreased likelihood of LDL-C above 100 g/dL (baseline 33% vs
      postintervention, 27%; P < .001). CONCLUSIONS: Significant changes in clinician
      performance of key quality measures were reported in patients with T2DM after a
      PI CME activity improved adherence to evidence-based recommendations of care.

PMID- 24451653
TI  - Avermectins differentially affect ethanol intake and receptor function:
      implications for developing new therapeutics for alcohol use disorders.
AB  - Our laboratory is investigating ivermectin (IVM) and other members of the
      avermectin family as new pharmaco-therapeutics to prevent and/or treat alcohol
      use disorders (AUDs). Earlier work found that IVM significantly reduced ethanol
      intake in mice and that this effect likely reflects IVM's ability to modulate
      ligand-gated ion channels. We hypothesized that structural modifications that
      enhance IVM's effects on key receptors and/or increase its brain concentration
      should improve its anti-alcohol efficacy. We tested this hypothesis by comparing
      the abilities of IVM and two other avermectins, abamectin (ABM) and selamectin
      (SEL), to reduce ethanol intake in mice, to alter modulation of GABAARs and
      P2X4Rs expressed in Xenopus oocytes and to increase their ability to penetrate
      the brain. IVM and ABM significantly reduced ethanol intake and antagonized the
      inhibitory effects of ethanol on P2X4R function. In contrast, SEL did not affect
      either measure, despite achieving higher brain concentrations than IVM and ABM.
      All three potentiated GABAAR function. These findings suggest that chemical
      structure and effects on receptor function play key roles in the ability of
      avermectins to reduce ethanol intake and that these factors are more important
      than brain penetration alone. The direct relationship between the effect of these
      avermectins on P2X4R function and ethanol intake suggest that the ability to
      antagonize ethanol-mediated inhibition of P2X4R function may be a good predictor
      of the potential of an avermectin to reduce ethanol intake and support the use of
      avermectins as a platform for developing novel drugs to prevent and/or treat
      AUDs.

PMID- 24451655
TI  - Effect of MAOA Genotype on Resting-State Networks in Healthy Participants.
AB  - Up to now, it remains unclear how monoamine oxidase A (MAOA), which has been
      repeatedly linked to aggression, affects brain activity within resting-state
      networks (RSN). Here, we used functional magnetic resonance imaging (fMRI) to
      test whether the MAOA genotype might influence activity within the common RSN.
      Our results demonstrate that during rest, participants with the low-activity
      genotype (MAOA-L) exhibit more activity within frontoparietal and temporal parts
      of the default mode network (DMN) and the cerebellum. The executive control and
      salience RSN revealed reduced activity for the MAOA-L group in several areas
      related to executive control, namely the right middle frontal gyrus (BA 6 and BA
      9), and the dorsal part of the anterior cingulate cortex. Participants with the
      high-activity genotype (MAOA-H) showed increased activity in the posterior
      cingulate part of the DMN. Taken together, we found widespread hyperactivity
      within the DMN and reduced activity in brain areas related to executive and
      inhibitory control for the MAOA-L group. We discuss how these first results
      examining the influence of MAOA on the resting brain might be related to previous
      findings regarding the genetics of aggression, while acknowledging that this is
      an exploratory study which needs further confirmation. 

PMID- 24451656
TI  - Hedonic Hotspots Regulate Cingulate-driven Adaptation to Cognitive Demands.
AB  - Positive hedonic states are known to attenuate the impact of demanding events on
      our body and brain, supporting adaptive behavior in response to changes in the
      environment. We used functional magnetic resonance imaging to examine the neural
      mechanism of this hedonic regulation. The effect of hedonic state (as induced by
      funny vs. neutral cartoons) on flexible behavioral and neural adaptation to
      cognitive demands was assessed in a flanker task in female volunteers. Behavioral
      results showed that humor reduced the compensatory adjustments to cognitive
      demands, as observed in sequential adaptations. This modulation was also
      reflected in midcingulate cortex (MCC; also known as the dorsal anterior
      cingulate cortex, ACC) activation. Furthermore, hedonic context increased
      activation in ventral striatum (VS) and ventral pallidum (VP). These hedonic
      hotspots attenuated the medial prefrontal cortex response to the cognitive
      demands in the ACC (also known as the rostral ACC). Activity in the ACC proved
      predictive of subsequent behavioral adaptation. Moreover, psychophysiological
      interaction analyses revealed that the MCC and the ACC were functionally
      connected with VS and VP, respectively. These observations reveal how MCC-VS and
      VP-ACC interactions are involved in the detection and hedonic modulation of
      behavioral adaptations to cognitive demands, which supports behavioral
      flexibility. 

PMID- 24451657
TI  - Functional Dopaminergic Neurons in Substantia Nigra are Required for Transcranial
      Magnetic Stimulation-Induced Motor Plasticity.
AB  - Repetitive magnetic stimulation (rTMS), including theta burst stimulation (TBS),
      is capable of modulating motor cortical excitability through plasticity-like
      mechanisms and might have therapeutic potential for Parkinson's disease (PD). An
      animal model would be helpful for elucidating the mechanism of rTMS that remain
      unclear and controversial. Here, we have established a TMS model in rat and
      applied this model to study the impact of substantia nigra dopamine neuron on TBS
      induced motor plasticity in PD rats. In parallel with human results, continuous
      TBS (cTBS) successfully suppressed motor evoked potentials (MEPs), while MEPs
      increased after intermittent TBS (iTBS) in healthy rats. We then tested the
      effect of iTBS in early and advanced 6-hydroxydopamine (6-OHDA)-lesioned PD.
      Moreover, dopaminergic neurons in substantia nigra and rotation behavior were
      assessed to correlate with the amount of iTBS-induced plasticity. In results,
      iTBS-induced potentiation was reduced in early PD rats and was absent in advanced
      PD rats. Such reduction in plasticity strongly correlated with the dopaminergic
      cell loss and the count of rotation in PD rats. In conclusion, we have
      established a TMS PD rat model. With the help of this model, we confirmed the
      loss of domaninergic neurons in substantia nigra resulting in reduced rTMS
      induced motor plasticity in PD. 

PMID- 24451658
TI  - The Rostro-Caudal Axis of Frontal Cortex Is Sensitive to the Domain of Stimulus
      Information.
AB  - Evidence suggests that lateral frontal cortex implements cognitive control
      processing along its rostro-caudal axis, yet other evidence supports a dorsal
      ventral functional organization for processes engaged by different stimulus
      domains (e.g., spatial vs. nonspatial). This functional magnetic resonance
      imaging study investigated whether separable dorsolateral and ventrolateral
      rostro-caudal gradients exist in humans, while participants performed tasks
      requiring cognitive control at 3 levels of abstraction with language or spatial
      stimuli. Abstraction was manipulated by using 3 different task sets that varied
      in relational complexity. Relational complexity refers to the process of
      manipulating the relationship between task components (e.g., to associate a
      particular cue with a task) and drawing inferences about that relationship. Tasks
      using different stimulus domains engaged distinct posterior regions, but within
      the lateral frontal cortex, we found evidence for a single rostro-caudal gradient
      that was organized according to the level of abstraction and was independent of
      processing of the stimulus domain. However, a pattern of dorsal/ventral
      segregation of processing engaged by domain-specific information was evident in
      each separable frontal region only within the most rostral region recruited by
      task demands. These results suggest that increasingly abstract information is
      represented in the frontal cortex along distinct rostro-caudal gradients that
      also segregate along a dorsal-ventral axis dependent on task demands. 

PMID- 24451659
TI  - Cerebral Lateralization is Protective in the Very Prematurely Born.
AB  - Individuals born prematurely are at risk for developmental delay, and converging
      data suggest alterations in neural networks in the developing preterm brain.
      Nevertheless, those critical period processes such as cerebral lateralization
      that underlie these findings remain largely unexplored. To test the hypothesis
      that preterm birth alters the fundamental program of corticogenesis in the
      developing brain, we interrogated cerebral lateralization at rest in very
      prematurely born participants and term controls at young adulthood. Employing a
      novel, voxel-based measure of functional connectivity, these data demonstrate for
      the first time that cerebral lateralization of functional connectivity in right
      hemisphere language homologs is altered for very preterm participants. Very
      preterm participants with no evidence for severe brain injury exhibited a
      significant decrease in right hemisphere lateralization in the right parietal and
      temporal lobes in this data driven analysis. Further, for the very preterm
      participants, but not the term participants, these fundamental alterations in the
      cerebral lateralization for language significantly correlate with language
      scores. These findings provide evidence that cerebral asymmetry is both plastic
      and experiential, and suggest the need for further study of underlying
      environmental factors responsible for these changes. 

PMID- 24451662
TI  - Manual rotation to decrease operative delivery in posterior or transverse
      positions: effect of rotation on perineal lacerations in forceps-assisted vaginal
      delivery.

PMID- 24451660
TI  - Evidence for Cerebellar Contributions to Adaptive Plasticity in Speech
      Perception.
AB  - Human speech perception rapidly adapts to maintain comprehension under adverse
      listening conditions. For example, with exposure listeners can adapt to heavily
      accented speech produced by a non-native speaker. Outside the domain of speech
      perception, adaptive changes in sensory and motor processing have been attributed
      to cerebellar functions. The present functional magnetic resonance imaging study
      investigates whether adaptation in speech perception also involves the
      cerebellum. Acoustic stimuli were distorted using a vocoding plus spectral-shift
      manipulation and presented in a word recognition task. Regions in the cerebellum
      that showed differences before versus after adaptation were identified, and the
      relationship between activity during adaptation and subsequent behavioral
      improvements was examined. These analyses implicated the right Crus I region of
      the cerebellum in adaptive changes in speech perception. A functional correlation
      analysis with the right Crus I as a seed region probed for cerebral cortical
      regions with covarying hemodynamic responses during the adaptation period. The
      results provided evidence of a functional network between the cerebellum and
      language-related regions in the temporal and parietal lobes of the cerebral
      cortex. Consistent with known cerebellar contributions to sensorimotor
      adaptation, cerebro-cerebellar interactions may support supervised learning
      mechanisms that rely on sensory prediction error signals in speech perception. 

PMID- 24451663
TI  - In reply.

PMID- 24451661
TI  - miRNAs are Essential for the Survival and Maturation of Cortical Interneurons.
AB  - Complex and precisely orchestrated genetic programs contribute to the generation,
      migration, and maturation of cortical GABAergic interneurons (cIN). Yet, little
      is known about the signals that mediate the rapid alterations in gene expression
      that are required for cINs to transit through a series of developmental steps
      leading to their mature properties in the cortex. Here, we investigated the
      function of post-transcriptional regulation of gene expression by microRNAs on
      the development of cIN precursors. We find that conditional removal of the
      RNAseIII enzyme Dicer reduces the number of cINs in the adult mouse. Dicer is
      further necessary for the morphological and molecular maturation of cINs. Loss of
      mature miRNAs affects cINs development by impairing migration and differentiation
      of this cell type, while leaving proliferation of progenitors unperturbed. These
      developmental defects closely matched the abnormal expression of molecules
      involved in apoptosis and neuronal specification. In addition, we identified
      several miRNAs that are selectively upregulated in the postmitotic cINs,
      consistent with a role of miRNAs in the post-transcriptional control of the
      differentiation and apoptotic programs essential for cIN maturation. Thus, our
      results indicate that cIN progenitors require Dicer-dependent mechanisms to fine
      tune the migration and maturation of cINs. 

PMID- 24451664
TI  - In reply.

PMID- 24451665
TI  - Maternal mortality: time for national action.

PMID- 24451666
TI  - In reply.

PMID- 24451667
TI  - Elective induction of labor at term compared with expectant management: maternal
      and neonatal outcomes.

PMID- 24451668
TI  - Contemporary labor patterns and maternal age.

PMID- 24451669
TI  - In reply.

PMID- 24451673
TI  - College publications.

PMID- 24451674
TI  - ACOG Practice Bulletin No.142: Cerclage for the management of cervical
      insufficiency.
AB  - The inability of the uterine cervix to retain a pregnancy in the second trimester
      is referred to as cervical insufficiency. Controversy exists in the medical
      literature pertaining to issues of pathophysiology, screening, diagnosis, and
      management of cervical insufficiency. The purpose of this document is to provide
      a review of current evidence of cervical insufficiency, including screening of
      asymptomatic at-risk women, and to offer guidelines on the use of cerclage for
      management. The diagnosis and management of other cervical issues during
      pregnancy, such as short cervical length, are discussed more in-depth in other
      publications of the American College of Obstetricians and Gynecologists.

PMID- 24451675
TI  - ACOG Committee Opinion No. 585: Health literacy.
AB  - According to the Institute of Medicine of the National Academies, health literacy
      is defined as the degree to which individuals have the capacity to obtain,
      process, and understand basic health information and services needed to make
      appropriate health decisions. The American College of Obstetricians and
      Gynecologists is committed to the promotion of health literacy for all.
      Responsibility for recognizing and addressing the problem of limited health
      literacy lies with all entities in the health care arena-from the system level to
      the health care professional.

PMID- 24451676
TI  - ACOG Committee Opinion No. 586: Health disparities in rural women.
AB  - Rural women experience poorer health outcomes and have less access to health care
      than urban women. Many rural areas have limited numbers of health care providers,
      especially women's health providers. Rural America is heterogeneous where
      problems vary depending on the region and state. Health care professionals should
      be aware of this issue and advocate for reducing health disparities in rural
      women.

PMID- 24451677
TI  - ACOG Committee Opinion No. 587: Effective patient-physician communication.
AB  - Physicians' ability to effectively and compassionately communicate information is
      key to a successful patient-physician relationship. The current health care
      environment demands increasing clinical productivity and affords less time with
      each patient, which can impede effective patient-physician communication. The use
      of patient-centered interviewing, caring communication skills, and shared
      decision making improves patient-physician communication. Involving advanced
      practice nurses or physician assistants may improve the patient's experience and
      understanding of her visit. Electronic communication with established patients
      also can enhance the patient experience in select situations.

PMID- 24451678
TI  - ACOG Technology Assessment No. 11: Genetics and molecular diagnostic testing.
AB  - Human genetics and molecular testing are playing an increasingly important role
      in medicine, including obstetric and gynecologic practice. As the genetic basis
      for reproductive disorders, common diseases, and cancer is elucidated with
      improved molecular technology, genetic testing opportunities are expanding and
      influencing treatment options and prevention strategies. It is essential that
      obstetrician-gynecologists be aware of advances in the understanding of genetic
      disease and the fundamental principles of genetic screening and molecular testing
      as genetics becomes a more integral part of routine medical practice. This
      document reviews the basics of genetic transmission and genetic technologies in
      current use.

PMID- 24451679
TI  - Phytoremediation of benzene, toluene, ethylbenzene and xylene contaminated air by
      D. deremensis and O. microdasys plants.
AB  - BACKGROUND: People usually spent about 90% of their time indoors, which are
      probably more polluted than outside the buildings. High levels of volatile
      organic compounds (VOCs) are known as causes of sick building syndrome. The
      present study was designed to determine the quantitative effects of some plants
      to improve the quality of the environmental air. RESULTS: D. deremensis and O.
      microdasys were chosen for the present study. There is no report of using O.
      microdasys for cleaning the air from pollutants. So, in this study, the
      effectiveness of O. microdasys in air removing from pollutants was studied and
      compared with D. dermensis.O. microdasys plant can remove 2 ppm concentration
      benzene, toluene, xylene and ethylbenzene from air in test chambers completely
      after 48, 55, 47 and 57 hours, respectively. The removal rates of benzene,
      toluene, xylene and ethylbenzene (BTEX) from air in the test chambers were 1.18,
      0.54, 1.64 and 1.35 mg/ m2d1, respectively. CONCLUSIONS: If an office containing
      2.5 ppm of each of BTEX and had an approximate volume of 30 m3, it contains 16,
      8, 22 and 22 mg/m3 benzene, toluene, xylene and ethylbenzene, respectively. Using
      ten O. microdasys pots with the same size used in this study, can remove benzene,
      toluene, xylene and ethylbenzene totally after 36, 40, 30 and 39 hours.The
      authors recommended studying the efficiency of the plants for removal of BTEX
      from air at higher range of concentrations such as 20-30 ppm.

PMID- 24451680
TI  - Spiracular air breathing in polypterid fishes and its implications for aerial
      respiration in stem tetrapods.
AB  - The polypterids (bichirs and ropefish) are extant basal actinopterygian (ray
      finned) fishes that breathe air and share similarities with extant lobe-finned
      sarcopterygians (lungfishes and tetrapods) in lung structure. They are also
      similar to some fossil sarcopterygians, including stem tetrapods, in having large
      paired openings (spiracles) on top of their head. The role of spiracles in
      polypterid respiration has been unclear, with early reports suggesting that
      polypterids could inhale air through the spiracles, while later reports have
      largely dismissed such observations. Here we resolve the 100-year-old mystery by
      presenting structural, behavioural, video, kinematic and pressure data that show
      spiracle-mediated aspiration accounts for up to 93% of all air breaths in four
      species of Polypterus. Similarity in the size and position of polypterid
      spiracles with those of some stem tetrapods suggests that spiracular air
      breathing may have been an important respiratory strategy during the fish
      tetrapod transition from water to land. 

PMID- 24451682
TI  - Pomegranate extract: a potential protector against aminoglycoside ototoxicity.
AB  - OBJECTIVE: To investigate the effectiveness of pomegranate extract as protection
      against aminoglycoside ototoxicity. DESIGN: Prospective, randomised, controlled,
      experimental study. SUBJECTS: Eighteen Wistar albino rats were randomly allocated
      to 5 days of either: saline injections; gentamicin injections; or pomegranate
      extract (100 ul/day via gavage) plus gentamicin injections. Distortion product
      otoacoustic emissions were tested before treatment and on day 3. After treatment,
      reactive oxygen species levels were measured in each rat's right cochlea and
      right kidney via chemiluminescence. RESULTS: Baseline emission amplitudes were
      similar. Post-treatment emissions differed significantly in the two treatment
      groups (p < 0.001). Cochlear reactive oxygen species levels were significantly
      higher in the gentamicin group (mean +/- standard deviation, 316.6 +/- 36.5
      relative light units per mg) than the gentamicin plus pomegranate extract group
      (240 +/- 24.6 relative light units per mg) (p = 0.004); control group levels were
      119.1 +/- 10.3 relative light units per mg. Renal reactive oxygen species levels
      were similar for the control and gentamicin plus pomegranate extract groups (p =
      0.59) but much higher in the gentamicin group (p = 0.004). CONCLUSION: Concurrent
      systemic pomegranate extract administration reduced reactive oxygen species level
      increases and otoacoustic emission changes, following aminoglycoside injection.

PMID- 24451681
TI  - Metabolic enzyme expression highlights a key role for MTHFD2 and the
      mitochondrial folate pathway in cancer.
AB  - Metabolic remodeling is now widely regarded as a hallmark of cancer, but it is
      not clear whether individual metabolic strategies are frequently exploited by
      many tumours. Here we compare messenger RNA profiles of 1,454 metabolic enzymes
      across 1,981 tumours spanning 19 cancer types to identify enzymes that are
      consistently differentially expressed. Our meta-analysis recovers established
      targets of some of the most widely used chemotherapeutics, including
      dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while
      also spotlighting new enzymes, such as the mitochondrial proline biosynthetic
      enzyme PYCR1. The highest scoring pathway is mitochondrial one-carbon metabolism
      and is centred on MTHFD2. MTHFD2 RNA and protein are markedly elevated in many
      cancers and correlated with poor survival in breast cancer. MTHFD2 is expressed
      in the developing embryo, but is absent in most healthy adult tissues, even those
      that are proliferating. Our study highlights the importance of mitochondrial
      compartmentalization of one-carbon metabolism in cancer and raises important
      therapeutic hypotheses. 

PMID- 24451684
TI  - 'Chaplains for well-being' in primary care: analysis of the results of a
      retrospective study.
AB  - AIM: To analyse quantitative changes in patient well-being concurrent with
      chaplaincy interventions in a retrospective study of a group of Primary Care
      centres in Sandwell and West Birmingham, United Kingdom. BACKGROUND: Anecdotal
      evidence suggests that support from trained Primary Care Chaplains may be
      particularly useful for those with subclinical mental health issues; it can
      reduce the tendency to 'medicalise unhappiness' and is a positive response to
      patients with medically unexplained symptoms. However, to date there has been no
      published research attempting to quantify their contribution. METHOD: Data were
      gathered from a group of Primary Care Centres, which make use of a shared
      Chaplaincy service. Demographic data and pre-post scores on the Warwick and
      Edinburgh Mental Wellbeing Scale (WEMWBS) were collected for patients who had
      attended consultations with a Chaplain. These were subjected to tests of
      statistical significance to evaluate the possible contribution of chaplaincy to
      patient well-being along with possible confounding variables. FINDINGS: a
      substantial improvement in WEMWBS scores (mean=9 points, BCa 95% CI [7.23,
      10.79], P=0.001) post-intervention. The improvement in scores was highest for
      those with initially lower levels of well-being. There is therefore evidence that
      chaplaincy interventions correlate with an improvement of holistic well-being as
      measured by a WEMWBS score. A prospective study on a larger scale would provide
      more detailed information on the interaction of possible variables. Further study
      is also required to evaluate the implications of this result for patient outcomes
      and GP resources. The efficacy of Primary Care Chaplaincy is under-researched and
      difficult to measure. This paper represents the first attempt to quantify a
      measurable improvement in the well-being of patients who are referred to the
      service.

PMID- 24451685
TI  - The electron-hole superfluidity in two coaxial nanotubes.
AB  - The superfluid phase and Coulomb drag effect caused by the pairing in a system of
      spatially separated electrons and holes in two coaxial cylindrical nanotubes are
      predicted. It is found that the drag resistance as a function of temperature
      experiences a jump at the critical temperature and can be used for the
      manifestation of the superfluid transition. It is demonstrated that at
      sufficiently low temperatures the order parameter and free energy density exhibit
      a kink due to the electron-hole asymmetry that is controlled by the radii of the
      nanotubes. 

PMID- 24451686
TI  - High-sensitivity cardiac troponin T predicts non-cardiac mortality in heart
      failure.
AB  - BACKGROUND:  Cardiac troponins are independent predictors of cardiac mortality in
      patients with heart failure (HF). Recently, elevation of troponins was described
      in non-cardiac diseases such as stroke and infection, among others, but it
      remains unclear whether high-sensitivity troponin T (hs-TnT) predicts non-cardiac
      mortality in HF patients. METHODS AND RESULTS:  Four-hundred and forty-four
      consecutive HF patients admitted to hospital for the treatment of decompensated
      HF were divided into 2 groups based on median hs-TnT: group L (<0.028ng/ml,
      n=220) and group H (>=0.028ng/ml, n=224). We compared all-cause mortality and
      echocardiographic findings between the 2 groups. In the follow-up period (mean
      472 days), 77 deaths (49 cardiac deaths and 28 non-cardiac deaths) were observed.
      The event-free rate was significantly lower in group H than in group L for non
      cardiac death (P=0.025), cardiac death (P<0.001), and all-cause mortality
      (P<0.001). On multivariate Cox proportional hazard analysis, high hs-TnT was
      found to be an independent predictor of non-cardiac death (P=0.042), cardiac
      death (P<0.001) and all-cause mortality (P<0.001) in HF patients after adjusting
      for risk factors. Regarding echocardiographic parameters, left ventricular wall
      thickness was higher (P<0.001), and ejection fraction was lower (P=0.011) in
      group H than in group L. CONCLUSIONS:  Hs-TnT is an independent predictor not
      only of cardiac mortality, but also of non-cardiac mortality in HF patients.

PMID- 24451687
TI  - Therapeutic effects of serelaxin in acute heart failure.
AB  - Over the past few decades, research on the peptide hormone, relaxin, has
      significantly improved our understanding of its biological actions under
      physiological and diseased conditions. This has facilitated the conducting of
      clinical trials to explore the use of serelaxin (human recombinant relaxin).
      Acute heart failure (AHF) is a very difficult to treat clinical entity, with
      limited success so far in developing new drugs to combat it. A recent phase-III
      RELAX-AHF trial using serelaxin therapy given during hospitalization revealed
      acute (ameliorated dyspnea) and chronic (improved 180-day survival) effects.
      Although these findings support a substantial improvement by serelaxin therapy
      over currently available therapies for AHF, they also raise key questions and
      stimulate new hypotheses. To facilitate the development of serelaxin as a new
      drug for heart disease, joint efforts of clinicians, research scientists and
      pharmacological industries are necessary to study these questions and hypotheses.
      In this review, after providing a brief summary of clinical findings and the
      pathophysiology of AHF, we present a working hypothesis of the mechanisms
      responsible for the observed efficacy of serelaxin in AHF patients. The existing
      clinical and preclinical data supporting our hypotheses are summarized and
      discussed. The development of serelaxin as a drug provides an excellent example
      of the bilateral nature of translational research. 

PMID- 24451688
TI  - Angular position of the cleat according to torsional parameters of the cyclist's
      lower limb.
AB  - OBJECTIVE: The aim of this work was to study the relationship of torsional and
      rotational parameters of the lower limb with a specific angular position of the
      cleat to establish whether these variables affect the adjustment of the cleat.
      DESIGN: Correlational study. SETTING: Motion analysis laboratory. PARTICIPANTS:
      Thirty-seven male cyclists of high performance. INTERVENTIONS: The variables
      studied of the cyclist's lower limb were hip rotation (internal and external),
      tibial torsion angle, Q angle, and forefoot adductus angle. MAIN OUTCOME
      MEASURES: The cleat angle was measured through a photograph of the sole and with
      an Rx of this using the software AutoCAD 2008. The variables were photograph
      angle (photograph), the variable denominated cleat-tarsus minor angle, and a
      variable denominated cleat-second metatarsal angle (Rx). Analysis included the
      intraclass correlation coefficient for the reliability of the measurements,
      Student's t test performed on the dependent variables to compare side, and the
      multiple linear regression models were calculated using the software SPSS 15.0
      for Windows. RESULTS: The Student's t test performed on the dependent variables
      to compare side showed no significant differences (P = 0.209 for the photograph
      angle, P = 0.735 for the cleat-tarsus minor angle, and P = 0.801 for the cleat
      second metatarsal angle). Values of R and R2 for the photograph angle model were
      0.303 and 0.092 (P = 0.08), the cleat/tarsus minor angle model were 0.683 and
      0.466 (P < 0.001), and the cleat/second metatarsal angle model were 0.618 and
      0.382, respectively (P < 0.001). CONCLUSIONS: The equation given by the model was
      cleat-tarsus minor angle = 75.094 - (0.521 * forefoot adductus angle) + (0.116 *
      outward rotation of the hips) + (0.220 * Q angle).

PMID- 24451689
TI  - Examining computerized software reliability to measure individual exposure time.
AB  - OBJECTIVE: Epidemiological sport injury research lacks relevance when all
      athletes are assumed to have equal time exposed to risk. Because athletes do not
      play equal minutes in ice hockey games, it is important to control for players'
      individual exposure times (IETs) when studying risk factors for injury. DESIGN:
      Cohort study. SETTING: Hockey games. PARTICIPANTS: Twenty-eight Minnesota Junior
      A hockey players. INTERVENTIONS: Individual exposure times were measured on all
      players dressed for their home games using both a manual (game clock, paper, and
      pencil) and a computer-based system [Time on Ice (TOI) software]. A sample of
      matched records was evaluated to compare the 2 methods of recording exposure.
      MAIN OUTCOME MEASURES: Values of individual player exposure times obtained by TOI
      software designed for hockey and the manual recording method were compared.
      RESULTS: Individual exposure times were measured simultaneously by computer-based
      and manual methods. For 26 games, it would require 156 hours to determine IET per
      game by the manual method. Conversely, IET totals on TOI software were computed
      automatically for each player per game. When IET was compared across periods and
      games, the computer analysis consistently totaled more IET than the manual
      method. CONCLUSIONS: Time on Ice software was user friendly, required no postgame
      processing, and showed a high degree of correlation to manually recorded times,
      although consistently higher IET per player per period than the manual method was
      noted.

PMID- 24451690
TI  - Determination of the criterion-related validity of hip joint angle test for
      estimating hamstring flexibility using a contemporary statistical approach.
AB  - OBJECTIVE: To examine the criterion-related validity of the horizontal hip joint
      angle (H-HJA) test and vertical hip joint angle (V-HJA) test for estimating
      hamstring flexibility measured through the passive straight-leg raise (PSLR) test
      using contemporary statistical measures. DESIGN: Validity study. SETTING:
      Controlled laboratory environment. PARTICIPANTS: One hundred thirty-eight
      professional trampoline gymnasts (61 women and 77 men). ASSESSMENT OF RISK
      FACTORS: Hamstring flexibility. MAIN OUTCOME MEASURES: Each participant performed
      2 trials of H-HJA, V-HJA, and PSLR tests in a randomized order. The criterion
      related validity of H-HJA and V-HJA tests was measured through the estimation
      equation, typical error of the estimate (TEEST), validity correlation (beta), and
      their respective confidence limits. RESULTS: The findings from this study suggest
      that although H-HJA and V-HJA tests showed moderate to high validity scores for
      estimating hamstring flexibility (standardized TEEST = 0.63; beta = 0.80), the
      TEEST statistic reported for both tests was not narrow enough for clinical
      purposes (H-HJA = 10.3 degrees; V-HJA = 9.5 degrees). Subsequently, the predicted
      likely thresholds for the true values that were generated were too wide (H-HJA =
      predicted value +/- 13.2 degrees; V-HJA = predicted value +/- 12.2 degrees).
      CONCLUSIONS: The results suggest that although the HJA test showed moderate to
      high validity scores for estimating hamstring flexibility, the prediction
      intervals between the HJA and PSLR tests are not strong enough to suggest that
      clinicians and sport medicine practitioners should use the HJA and PSLR tests
      interchangeably as gold standard measurement tools to evaluate and detect short
      hamstring muscle flexibility.

PMID- 24451691
TI  - Wheelchair marathon creates a systemic anti-inflammatory environment in persons
      with spinal cord injury.
AB  - OBJECTIVE: To investigate interleukin (IL)-6 and other inflammation markers in
      athletes with spinal cord injury (SCI) during a wheelchair marathon race. DESIGN:
      Nonrandomized study in an actual race. SETTING: The 28th Oita International
      Wheelchair Marathon Race, Japan. PARTICIPANTS: Twenty-eight men with SCI between
      T7 and L2 (16 full-marathon racers, full-group; and 12 half-marathon racers, half
      group). MAIN OUTCOME MEASURES: Plasma IL-6, tumor necrosis factor (TNF)-alpha,
      and high-sensitivity C-reactive protein (hsCRP) were measured the day before,
      immediately after the race, and 2 hours after the race. RESULTS: Plasma IL-6
      concentrations increased by 18.4-fold and by 9.4-fold (P < 0.05) in the full- and
      half-groups immediately after the race (P < 0.05), respectively, but returned to
      baseline at 2 hours of recovery. In contrast, plasma TNF-alpha and hsCRP did not
      change throughout the race in both groups. The fold change in plasma IL-6
      immediately after the race relative to the prerace was significantly higher in
      the full-group than the half-group (P < 0.05). In both groups, plasma IL-6
      immediately after the race did not correlate with the average wheelchair speed.
      Interestingly, plasma IL-6 and hsCRP before the race in the full-group, but not
      in half-group, correlated negatively with the average wheelchair speed (P <
      0.05). CONCLUSIONS: The study demonstrated that half- and full-marathon
      wheelchair races increased plasma IL-6, but not TNF-alpha and hsCRP. Furthermore,
      the top athletes of the full-group had low plasma IL-6 and hsCRP at baseline.
      Wheelchair marathon competition, especially full-marathon, and daily training
      seem to have beneficial effects on SCI through the plasma IL-6 response.

PMID- 24451692
TI  - Plantar cutaneous sensitivity and balance in individuals with and without chronic
      ankle instability.
AB  - OBJECTIVE: To determine if plantar cutaneous sensation and postural control
      differ between individuals with and without chronic ankle instability (CAI).
      DESIGN: Case-control. SETTING: Laboratory. PARTICIPANTS: Ten subjects with CAI
      and 10 subjects with no ankle sprain history participated. INTERVENTIONS: Light
      touch was evaluated at 3 sites (heel, base of fifth metatarsal, and head of first
      metatarsal) on the plantar aspect of the foot using Semmes-Weinstein
      Monofilaments (SWMs). Postural control was assessed using the single leg firm and
      foam conditions of the Balance Error Scoring System (BESS) and during eyes open
      and eyes closed static postural control on a force plate. MAIN OUTCOME MEASURES:
      Semmes-Weinstein Monofilament detection thresholds, BESS errors, and the mean of
      time-to-boundary (TTB) minima (TTB-mean) and the SD of TTB minima (TTB-SD) in the
      anterior-posterior (AP) and medial-lateral directions were evaluated for each
      subject. RESULTS: Subjects with CAI demonstrated increased SWM detection
      thresholds at the heel (P = 0.009), head of the first (P = 0.01), and base of the
      fifth metatarsal (P < 0.001) and postural control deficits on the BESS firm (P =
      0.04) and foam (P = 0.001) conditions and with eyes open TTB-mean AP (P = 0.007)
      and TTB-SD AP (P = 0.02). When combining groups, a negative moderate correlation
      was observed between the base of the fifth metatarsal detection threshold and
      eyes open TTB-mean AP (r = -0.50; P = 0.03). CONCLUSIONS: Light touch and
      postural control deficits were observed in individuals with CAI. The correlation
      between light touch over the base of the fifth metatarsal and eyes open TTB-mean
      AP suggests that there may be a relevant relationship between these measures.
      CLINICAL RELEVANCE: Individuals with CAI demonstrated deficits in light touch
      over the plantar aspect of the foot. The relationship between base of the fifth
      metatarsal sensation and TTB-mean AP may provide a starting point to link plantar
      cutaneous sensory deficits to changes in other aspects of sensorimotor function.

PMID- 24451693
TI  - Cardiovascular preparticipation screening practices of college team physicians.
AB  - OBJECTIVE: Determine the cardiovascular screening practices of college team
      physicians. DESIGN: Cross-sectional survey. SETTING: Electronic mail with a link
      to a 9-item survey. PARTICIPANTS: American Medical Society for Sports Medicine
      college team physicians. INTERVENTIONS: Screening practices survey administered
      to college team physicians. MAIN OUTCOME MEASURES: Cardiovascular
      preparticipation screening practices including noninvasive cardiac screening
      (NICS) such as electrocardiogram (ECG) or echocardiogram. RESULTS: Two hundred
      twenty-four of 613 AMSSM members identifying themselves as college team
      physicians (36.5%) responded: National Collegiate Athletic Association Division
      I: 146, Division II: 41, Division III: 27, National Association of
      Intercollegiate Athletics: 8, and Junior College: 2. The majority (78%) of
      schools conducted the American Heart Association (AHA) 12-element history and
      physical examination. Division I institutions were more likely to add an ECG
      and/or echocardiogram (30%) to their preparticipation examination (PPE) compared
      with lower divisions (P < 0.0001). Those Division I schools using NICS were more
      likely to do so for all athletes (P < 0.001) or revenue generating sports (P <
      0.001), whereas other institutions did so only for high-risk subgroups (P <
      0.01). Lower division schools would consider adding ECG if it cost less (P =
      0.01) or if there were more local expertise in athlete-specific interpretation
      standards (P = 0.04). CONCLUSIONS: Many National Collegiate Athletic Association
      Athletes Division I programs already use NICS to screen athletes, whereas a
      significant portion of lower division schools add ECG for athletes deemed high
      risk. Increased use of these modalities suggests limitations of traditional PPE
      screening methods. CLINICAL RELEVANCE: This is the first study to assess cardiac
      screening practices across all collegiate divisions and broadens our
      understanding of cardiac screening in high-level athletes.

PMID- 24451694
TI  - Concussion surveillance: do low concussion rates in the Qatar Professional
      Football League reflect a true difference or emphasize challenges in knowledge
      translation?
AB  - OBJECTIVE: To investigate concussion epidemiology in the first football (soccer)
      division of Qatar. DESIGN: Prospective cohort study. SETTING: Professional First
      Division Football League of Qatar. PARTICIPANTS: All first team players were
      included at the beginning of each season. INTERVENTIONS: Daily collection of
      training and match exposure from August 2008 until April 2012 by club medical
      staff. Head injuries during training and match play were recorded on standardized
      injury cards. MAIN OUTCOME MEASURES: Injury incidence was calculated as number of
      injuries per hour exposed to risk and expressed as rate per 1000 hours. RESULTS:
      The incidence of concussions in professional club football in Qatar is 0.016
      (0.000-0.033) per 1000 hours of exposure. CONCLUSIONS: The concussion incidence
      is only 25% of that in the previous European studies using the same time loss
      injury definition. This raises the possibility that concussions are
      underreported. Further research is necessary. In the meantime, concussion
      education of players, club medical, and support staff is warranted, in keeping
      with the Zurich concussion consensus call for the need for an increase in
      knowledge translation.

PMID- 24451695
TI  - Injury profile of mixed martial arts competitors.
AB  - OBJECTIVE: To provide an updated comprehensive profile of mixed martial arts
      (MMAs) injuries. DESIGN: Correlational and multivariate analyses were conducted
      on cross-sectional data to examine injuries sustained during 711 MMA bouts. One
      physician diagnosed any injuries occurring during the bouts. SETTING: Various
      sports venues in Kansas and Missouri holding MMA competitions. PARTICIPANTS: Male
      and female and amateur and professional MMA competitors contributing to 1422
      fight participations (fight participations = 711 bouts * 2 fighters/bout).
      INDEPENDENT VARIABLES: State, level (amateur or professional), gender, number of
      rounds, and bout outcome (knockout/technical knockout [KO/TKO] vs other outcomes
      [eg, decision]). MAIN OUTCOME MEASURES: Injuries/fight participations, injury
      sustained (yes vs no), and fighter referred to emergency room (ER; yes vs no).
      RESULTS: The overall injury rate was 8.5% of fight participations (121
      injuries/1422 fight participations) or 5.6% of rounds (121/2178 rounds). Injury
      rates were similar between men and women, but a greater percentage of the
      injuries caused an altered mental state in men. The risk of being injured was
      significantly greater for bouts held in Kansas, at the professional level,
      lasting more rounds, and ending in a KO/TKO. Fighters also were more likely to be
      referred to the ER if they participated in longer bouts ending in a KO/TKO.
      CONCLUSIONS: The observed injury rate was lower than previously reported
      suggesting recent regulatory changes have made MMA a safer sport. Increased
      clinical awareness and additional research should be extended to head-related
      injuries in MMAs especially those associated with KOs/TKOs.

PMID- 24451696
TI  - Assessment of muscle architecture of the biceps femoris and vastus lateralis by
      ultrasound after a chronic stretching program.
AB  - OBJECTIVE: To evaluate the chronic effects of a static stretching program on the
      muscle architecture of biceps femoris (BF) and vastus lateralis (VL) muscles in
      ultrasound (US) images. DESIGN: Randomized controlled longitudinal trial.
      SETTING: Biomechanics Laboratory of Physical Education School of the Army, Rio de
      Janeiro, Brazil. PARTICIPANTS: The study included 24 healthy and physically
      active male volunteers (19.05 +/- 1.40 years, 1.73 +/- 0.07 m, and 73.15 +/- 8.33
      kg), randomly allocated to 1 of 2 groups: stretching group (SG, n = 12) and
      control group (n = 12). INTERVENTIONS: The SG was submitted to 3 sets of 30
      seconds of static stretching 3 times a week during 8 weeks. MAIN OUTCOME
      MEASURES: Ultrasound equipment (7.5 MHz) was used for the evaluation of BF and VL
      muscle architecture variables (pennation angle, fiber length, muscle thickness,
      and fascicle displacement) before and after training. Knee range of motion (ROM)
      and isometric flexion and extension torque (TQ) were also measured. RESULTS:
      There were no significant changes in muscle architecture, TQ, and maximum knee
      flexion angle (P > 0.05). However, maximum knee extension angle (MEA) increased
      significantly in the SG (pretraining: 159.37 +/- 7.27 degrees and posttraining:
      168.9 +/- 3.7 degrees; P < 0.05). CONCLUSIONS: Volume or intensity (or both) of
      the stretching protocol was insufficient to cause structural changes in the VL
      and BF muscles. The increase in MEA could not be explained by muscle architecture
      changes. CLINICAL RELEVANCE: To describe changes in the VL and BF muscle tendon
      unit using US after a long-term stretching program to identify which structures
      are responsible for ROM increase.

PMID- 24451697
TI  - The ergogenic effect of long-term use of high dose salbutamol.
AB  - OBJECTIVE: Investigate the effect of inhaling 1600 MUg salbutamol for 6 weeks on
      endurance, strength, and power performances. DESIGN: Randomized double-blind,
      mixed-model repeated measures. PARTICIPANTS: Sixteen male athletes (mean +/- SD:
      age, 20.1 +/- 1.6 years; height, 179.9 +/- 8.2 cm; weight, 74.6 +/- 9.1 kg).
      INTERVENTIONS: Participants were assigned to either a placebo inhaler (PLA) or
      inhaled 1600 MUg salbutamol group (SAL). Over 6 weeks, participants inhaled PLA
      or SAL and completed 4 training sessions per week that focused on endurance,
      strength, and power. MAIN OUTCOME MEASURES: Participants completed the
      assessments of peak oxygen consumption (V[Combining Dot Above]O2peak), 3-km time
      trial, vertical jump height, 1 repetition maximum (1RM) bench and leg press, and
      peak torque knee flexion and extension. Assessments were undertaken at baseline,
      week 3, and week 6. RESULTS: Over the 6 weeks, PLA and SAL groups improved
      V[Combining Dot Above]O2peak (51.7 +/- 4.7 vs 56.8 +/- 7.1 mL.min.kg; 53.1 +/-
      6.1 vs 55.0 +/- 6.7 mL.min.kg); 3-km running time trial (988.6 +/- 194.6 vs 947.5
      +/- 155.5 seconds; 1040.4 +/- 187.4 vs 1004.2 +/- 199.4 seconds); 1RM bench press
      (65.7 +/- 15.4 vs 70.3 +/- 13.8 kg; 64.3 +/- 14.0 vs 72.5 +/- 15.3 kg); and leg
      press (250.0 +/- 76.4 vs 282.5 +/- 63.6 kg; 217.9 +/- 54.0 vs 282.8 +/- 51.9 kg).
      The SAL group did not improve significantly greater in any endurance or strength
      and power measure when compared with the PLA group. CONCLUSIONS: Inhaling 1600 ug
      salbutamol daily over 6 weeks does not result in significant improvements in
      endurance, or strength and power performances. CLINICAL RELEVANCE: Athletes using
      inhaled salbutamol to treat bronchoconstriction during exercise on a daily basis
      will not gain an advantage over nonasthmatic athletes not using inhaled
      salbutamol.

PMID- 24451698
TI  - Does ulnar variance change with age and what is the influence of training and
      biological characteristics in this change? A short-term longitudinal study in
      Portuguese artistic gymnasts.
AB  - OBJECTIVE: To analyze the variability and longitudinal stress-related changes in
      ulnar variance (UV) in a group of immature artistic gymnasts. The relationship
      between UV and a group of biological and training variables was also
      investigated. DESIGN: Prospective cohort study. SETTING: Portuguese Federation of
      Gymnastics. PARTICIPANTS: Twenty-five Portuguese skeletally immature gymnasts
      competing nationally. ASSESSMENT OF RISK FACTORS: Skeletal age (Tanner-Whitehouse
      3 method), stature, body mass and body mass index (BMI) (Seca stadiometer), fat
      free mass and percentage of body fat mass (Tanita BC 418), handgrip strength
      (Takei dynamometer), and training data (interview). MAIN OUTCOME MEASURES: To
      determine UV stress-related changes over time, left UV was obtained using Hafner
      procedure. Ulnar variance values and biological characteristics were tested twice
      (at baseline and after 18 months of training). RESULTS: Analysis of covariance
      analysis presented a significant interaction between age and time effect in UV at
      baseline. Each category of UV reacted differently to the interaction between age
      and training time. Significant relationships between UV and biological and
      training variables (chronological and skeletal age, body mass, BMI, handgrip
      strength, hour per week, and years of training) were evident in at least one of
      the moments of data collection. CONCLUSIONS: The gymnasts showed significant
      longitudinal UV changes toward less negative UV over the training period.
      Nevertheless, we could not find a significant correlation between UV and the
      majority of the researched variables. Thus, although UV has been broadly studied,
      this phenomenon is complex because it depends on different intrinsic and
      extrinsic factors that are difficult to control, making necessary additional
      research on this topic. CLINICAL RELEVANCE: The gymnast's wrist has been
      associated with a high incidence of painful symptomatology and injuries, leading
      to the formulation of several hypotheses related to the UV ethiology. Knowledge
      about the possible intrinsic or extrinsic factors related to UV changes and/or
      different UV categories (negative, neutral, and positive), as well as their
      consequent specific injuries in gymnasts' wrists may contribute to a primary
      prevention or reduction in the occurrence, recurrence and severity of pain,
      functional disability, or injuries in radius-ulnocarpal joint, thereby improving
      gymnasts' performance.

PMID- 24451699
TI  - Reductions in intraocular pressure after acute aerobic exercise: a meta-analysis.
AB  - OBJECTIVE: Aerobic exercise is known to reduce elevated intraocular pressure
      (IOP), a primary risk factor for a disease of the eye known as primary open-angle
      glaucoma. Given the disparate nature of experimental protocols across the
      literature, an analysis of studies on the effect of acute aerobic exercise on IOP
      is necessary to verify the influence of participant characteristics, exercise
      intensity, and duration. DATA SOURCES: The electronic databases PubMed, Web of
      Science, and Embase were searched, producing 35 empirical studies for review. Ten
      studies producing 14 independent groups were chosen as per the criteria of the
      analysis. MAIN RESULTS: Random effects model was used to produce subgroup
      analyses, and meta-regressions were used to verify the impact of group
      allocation, intensity, and duration on the interstudy variability of the effect
      size (ES). The outcome variable of postexercise change in IOP produced a
      significant effect of exercise, almost 2-fold greater for sedentary populations
      than for normally active populations (ES = -4.198; confidence interval, -5.151 to
      -3.245); ES = -2.340; confidence interval, -3.305 to 1.375, respectively). The
      significant effect of exercise on IOP is potentially mediated by group
      allocation. Intensity and duration do not contribute to the overall ES nor do
      they explain the difference between sedentary and normally active populations.
      CONCLUSIONS: There is a robust effect of exercise on IOP for sedentary
      participants. However, the heterogeneity across study parameters, such as
      exercise protocol, IOP measurement, and participant selection, prohibited the
      inclusion of studies in this analysis that may have influenced the results. The
      current analysis makes clear the need for standardization of protocol across this
      field of research.

PMID- 24451701
TI  - Adjuvant therapy for older women with early-stage breast cancer: treatment
      selection in a complex population.
AB  - Breast cancer is a disease of aging. However, older women with breast cancer are
      less likely to participate in clinical trials or to receive recommended
      treatment. This undertreatment has contributed to a lag in breast cancer survival
      outcomes for older women compared with that for their younger counterparts. The
      principles that govern recommendations for adjuvant treatment of breast cancer
      are the same for younger and older women. Systemic adjuvant treatment
      recommendations should be offered on the basis of tumor characteristics that
      divide patients into three distinct subgroups. These include (1) older women with
      hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)
      negative breast cancer who should be offered endocrine therapy; (2) older women
      with HR-negative and HER2-negative breast cancer who should be offered adjuvant
      chemotherapy; and (3) older women with HER2-positive disease who should be
      offered chemotherapy with trastuzumab. Exceptions to these guidelines may be made
      for older women with small node-negative tumors or frail older women with limited
      life expectancy, where close surveillance may be a reasonable alternative.
      Addressing the current age-related disparities in breast cancer survival will
      require that older women are offered the same state-of-the-art-treatment as their
      younger counterparts, with a careful weighing of the risks and benefits of each
      treatment in the context of the individual's preferences. In addition, older
      women should be encouraged to participate in breast cancer clinical trials to
      generate additional chemotherapy efficacy, toxicity, and quality of life data. 

PMID- 24451700
TI  - Thoracic outlet syndrome in a patient with absent scalenus anterior muscle.
AB  - This case report describes the rare anomaly of an absent right anterior scalene
      muscle presenting with the symptoms and signs of the thoracic outlet syndrome.
      The thoracic outlet syndrome in our patient can be attributed to the absence of
      the right anterior scalene muscle, which resulted in the brachial plexus being in
      proximity to the subclavian vein and artery in a narrowed and abnormal
      interscalene space. In addition, the absence of the anterior scalene muscle
      resulted in the neurovascular structures being compressed onto the first rib in
      the costoclavicular space. The most likely cause of the presentation is, however,
      the possibility of the presence of aberrant muscle slips, which would cause
      compression of the structures in the anterior (venous) and posterior
      (neurological) sections of the thoracic outlet.

PMID- 24451702
TI  - Management of Small T1a/b N0 Breast Cancers.
AB  - T1ab N0 breast cancer generally has excellent prognosis. Adverse prognostic
      factors include HER2+ disease, ER-negative disease, high-grade histology, T1b,
      and young age of patient. These patients are largely excluded from most trials,
      and to date, no prospective studies for this group yet reported. Treatment
      guidelines are vague and treatment inconsistent. As yet, in the HER2+ population,
      little experience with targeted therapy has been reported. Prospective trials are
      needed. 

PMID- 24451703
TI  - Controversies in adjuvant endocrine therapy for breast cancer.
AB  - Adjuvant endocrine therapy for early-stage breast cancer has had the single
      biggest impact on improving survival from the disease-with tamoxifen alone
      contributing to saving many thousands of lives. In postmenopausal women,
      additional progress has been made by the incorporation of aromatase inhibitors
      into the treatment of early-stage, estrogen receptor (ER)-positive breast cancer,
      as several large well-conducted trials have established either "up-front" or
      "switch" strategies that are now widely used. To date, both have been shown to be
      beneficial when compared with tamoxifen alone, although controversy exists as to
      which approach is superior. Increasingly, extended adjuvant therapy is being
      considered, as "longer may be better" for some women who have an ongoing risk of
      recurrence beyond 5 years. However, controversy remains as to how long adjuvant
      endocrine therapy should be given for; in clinical practice, clinicians balance
      the level of risk for individual patients versus any ongoing toxicity concerns.
      For premenopausal women, with ER-positive breast cancer, tamoxifen remains the
      gold standard with uncertainty in the added overall benefit of ovarian
      suppression. Important clinical trials have recently been completed that may help
      answers this question, including whether complete estrogen deprivation using a
      luteinizing hormone releasing hormone (LHRH) agonist plus aromatase inhibitors
      (AIs) is of added benefit. In recent years, molecular profiling of ER-positive
      breast cancer has started to distinguish those women with a low risk of
      recurrence on endocrine therapy who may not need chemotherapy. Thus, with more
      therapy options and greater tumour stratification, modern, adjuvant endocrine
      therapy is becoming increasingly personalised to suit each individual patient's
      risk. 

PMID- 24451704
TI  - A dickens tale of the treatment of advanced breast cancer: the past, the present,
      and the future.
AB  - Metastatic breast cancer (MBC), a usually incurable disease, continues to vex
      physicians and patients. Recent decades have seen great improvements in the
      treatment of MBC, based on the availability of novel targeted therapeutics and
      more standard chemotherapeutic agents. This article describes the goals of
      therapy for MBC, the progress made against MBC in recent decades, the current
      standard of care, and the ongoing efforts of basic and translational researchers
      to transfer the fruits of modern scientific discovery to patients in the clinic. 

PMID- 24451705
TI  - Ductal carcinoma in situ: challenges, opportunities, and uncharted waters.
AB  - Ductal carcinoma in situ (DCIS) is a heterogeneous group of diseases that differ
      in biology and clinical behavior. Until 1980, DCIS represented less than 1% of
      all breast cancer cases. With the increased utilization of mammography, DCIS now
      accounts for 15% to 25% of newly diagnosed breast cancer cases in the United
      States. Although our ability to detect DCIS has radically improved, our
      understanding of the pathophysiology and factors involved in its progression to
      invasive carcinoma is still poorly defined. In many patients, DCIS will never
      progress to invasive breast cancer and these women are overtreated. In contrast,
      some DCIS cases are clinically aggressive and the women may be undertreated. We
      are able to define some of the predictors of aggressive DCIS compared with DCIS
      of low malignant potential. However, our ability to risk-stratify DCIS is still
      in its infancy. Clinical risk factors that predict aggressive disease and
      increased risk of local recurrence include young age at diagnosis, large lesion
      size, high nuclear grade, comedo necrosis, and involved margins. Treatment
      factors such as wider surgical margins and radiation therapy reduce the risk of
      local recurrence. DCIS represents a key intermediate in the stepwise progression
      to malignancy, but not all aggressive breast cancers appear to have a DCIS
      intermediate, notably within triple-negative breast cancer. Ongoing studies of
      the genetic and epigenetic alterations in precancerous breast lesions (atypia and
      DCIS) as well as the breast microenvironment are important for developing
      effective early detection and individualized targeted prevention. 

PMID- 24451706
TI  - Ductal carcinoma in situ, and the influence of the mode of detection, population
      characteristics, and other risk factors.
AB  - Approximately 25% of breast cancers in the United States are diagnosed as ductal
      carcinoma in situ (DCIS). Rates of DCIS have risen from 5.8 per 100,000 women in
      the 1970s to 32.5 per 100,000 in 2004. This pattern is generally attributed to
      increased use of screening mammography. DCIS is a major risk factor for invasive
      breast cancer, and considerable controversy remains about whether DCIS should be
      considered a direct precursor of invasive breast cancer. There is, however, a
      general consensus that DCIS represents an intermediate step between normal breast
      tissue and invasive breast cancer. Although the majority of major risk factors
      are similar for DCIS and invasive breast cancer, prognostic factors including
      estrogen and progesterone receptor status and HER2 positivity are less well
      studied but look to have similar value in both cases. The use of postdiagnostic
      MRI, sentinel lymph node biopsy, surgery, radiation, and endocrine therapy are
      all evolving as evidence from randomized and observational studies continues to
      accumulate. Treatment of DCIS requires a balance between risk of overtreatment
      and undertreatment. Ongoing studies are focusing on whether partial-breast
      irradiation is as effective as whole-breast irradiation and whether treatment
      with endocrine therapies can reduce the likelihood of either invasive breast
      cancer or DCIS recurrence. In general, treatment decisions should take into
      account the likelihood that an apparent case of DCIS could harbor foci of
      invasive disease. 

PMID- 24451707
TI  - Postmastectomy radiation and partial breast irradiation.
AB  - Between 1997 and 1999, three modern postmastectomy radiation therapy (PMXRT)
      trials were published. These trials showed a significant benefit with respect to
      local control and survival in women who received adjuvant radiation after
      mastectomy. Despite two decades of follow-up, reanalyses, meta-analyses and
      vigorous and often acrimonious debate, questions about the benefit of PMXRT in
      women with one to three positive lymph nodes (LNs) remain unanswered for many.
      This persistent debate has limited the use of PMXRT. A treatment concept certain
      to be as vigorously debated as that of PMXRT is that of partial breast
      irradiation (PBI). However, unlike PMXRT, the acceptance of PBI, by community
      physicians, has been nothing short of meteoric and represents the first major
      shift in the local therapy paradigm in more than 10 years. Herein, information
      will be presented that will suggest we are nearing the end of one debate-PMXRT in
      patients with one to three positive LNs-and beginning another-appropriateness of
      PBI. 

PMID- 24451708
TI  - The appropriate extent of surgery for early-stage breast cancer.
AB  - Attitudes regarding the appropriate extent of surgery for breast cancer and the
      effect of surgery on breast cancer-specific survival have varied over time.
      Failure to maintain local control is associated with decreased survival, but the
      extent of surgery necessary for local control has decreased as other treatment
      modalities, such as radiotherapy and systemic therapy, have become more widely
      used. Both endocrine therapy and chemotherapy considerably reduce rates of local
      recurrence in the breast, as well as the incidence of contralateral breast
      cancer, and as efficacy in reducing metastatic disease increases, so does the
      benefit in reducing local recurrence. The excellent rates of local control in the
      ACOSOG Z11 trial after elimination of axillary dissection in patients with
      positive sentinel nodes receiving whole-breast irradiation and systemic therapy
      are a model for reducing surgical morbidity in the era of multimodality therapy. 

PMID- 24451709
TI  - How does biology affect local therapy decisions?
AB  - Breast cancer represents a biologically diverse set of diseases. Previous data
      suggest that the estrogen/progesterone receptor (ER/PR) status and HER2/neu
      status are important determinants of prognosis and response to various systemic
      treatments. Recent data also suggest that these receptors correlate with outcomes
      of local-regional therapies. Specifically, patients with ER-positive HER2/neu
      negative disease have an excellent outcome with radiation treatments, either
      given as a component of breast-conservative therapy (BCT) or for those with more
      advanced disease, when given after mastectomy. For patients with triple-negative
      disease, data suggest that the proportional benefits offered from radiation in
      reducing local-regional recurrences may be less. This article will highlight some
      of these data and discuss strategies for new local-regional research avenues that
      are based on breast cancer biologic subtype. 

PMID- 24451710
TI  - Clinical and imaging surveillance following breast cancer diagnosis.
AB  - Breast cancer is the most common malignancy affecting women worldwide. Women have
      a 1 in 8 lifetime risk of breast cancer. Breast conservation therapy (BCT) is the
      most common method of definitive treatment. Patients who previously have had to
      undergo mastectomy may be now eligible for BCT or a multitude of options for
      reconstruction, either immediate or delayed. Surveillance imaging after a breast
      cancer diagnosis is important because there is an increased risk of recurrence
      developing in patients, and early detection has been shown to improve survival.
      There is currently no consensus on a protocol for imaging the postoperative
      breast. In patients who have undergone mastectomy, detection of recurrence has
      mostly been via clinical symptoms and physical exam, often at a later stage. New
      imaging modalities, such as magnetic resonance imaging (MRI), ultrasound (US),
      and positron emission mammography (PEM) are changing the way we image the
      postsurgical breast. MRI, coupled with physical exam and mammography, approaches
      100% sensitivity and high specificity for the identification of recurrent
      disease. We present a review of major academic institutions' imaging protocols
      and discuss the advantages of including MRI in traditional mammographic and
      clinical exams. 

PMID- 24451711
TI  - Advanced imaging techniques for the detection of breast cancer.
AB  - Mammography is the only breast imaging examination that has been shown to reduce
      breast cancer mortality. Population-based sensitivity is 75% to 80%, but
      sensitivity in high-risk women with dense breasts is only in the range of 50%.
      Breast ultrasound and contrast-enhanced breast magnetic resonance imaging (MRI)
      have become additional standard modalities used in the diagnosis of breast
      cancer. In high-risk women, ultrasound is known to detect approximately four
      additional cancers per 1,000 women. MRI is exquisitely sensitive for the
      detection of breast cancer. In high-risk women, it finds an additional four to
      five cancers per 100 women. However, both ultrasound and MRI are also known to
      lead to a large number of additional benign biopsies and short-term follow-up
      examinations. Many new breast imaging tools have improved and are being developed
      to improve on our current ability to diagnose early-stage breast cancer. These
      can be divided into two groups. The first group is those that are advances in
      current techniques, which include digital breast tomosynthesis and contrast
      enhanced mammography and ultrasound with elastography or microbubbles. The other
      group includes new breast imaging platforms such as breast computed tomography
      (CT) scanning and radionuclide breast imaging. These are exciting advances.
      However, in this era of cost and radiation containment, it is imperative to look
      at all of them objectively to see which will provide clinically relevant
      additional information. 

PMID- 24451712
TI  - Update of the oxford overview: new insight and perspectives in the era of
      personalized medicine.
AB  - There is great appreciation for the heterogeneity of breast cancers, particularly
      of hormone-receptor positive breast cancers. A goal of modern oncology managing
      such heterogeneity is to determine how to individualize therapy based on the
      specific pathological and biological features of a given tumor. Two distinctive
      clinical literatures exist to guide treatment of hormone-receptor-positive breast
      cancer. The Oxford Overview, a seminal meta-analysis effort, has recently been
      updated, and suggests that nearly all patients with ER-positive tumors benefit
      from adjuvant endocrine therapy. In addition, the overview finds that nearly all
      subsets of patients with ER-positive tumors also benefit from modern adjuvant
      chemotherapy regimens. Meanwhile, retrospective subset analyses of specific
      trials or populations suggests that the benefits of chemotherapy are not so
      uniform, and in particular that molecular diagnostics assays can identify
      patients who do not warrant chemotherapy. This article will highlight recent data
      and controversies in personalizing adjuvant breast cancer therapy. 

PMID- 24451713
TI  - Gene patents and personalized medicine.
AB  - The use of genetic information to design and guide therapies and to develop novel
      diagnostic procedures creates important patent issues. Patents on human gene
      sequences have likely helped stimulate the introduction of new biologics;
      however, their role and that of patents on genotype-phenotype correlations in
      diagnostic testing is highly controversial. Genotype-phenotype associations are
      at the heart of personalized medicine. The intellectual property rules by which
      these biologic relationships are governed have profound implications for the
      growth of individualized medicine. 

PMID- 24451714
TI  - Chemoprevention for breast cancer: overcoming barriers to treatment.
AB  - Evidence from placebo-controlled, randomized clinical trials supports the use of
      chemoprevention in women at high risk for developing breast cancer, and two
      agents-tamoxifen and raloxifene-are U.S. Food and Drug Administration (FDA)
      approved for the indication. Despite clinical guidelines that recommend
      physicians counsel high-risk women about the use of chemoprevention and the
      estimated 2.4 million women in the United States who meet eligibility criteria
      for net benefit, the uptake of breast cancer chemoprevention has been exceedingly
      low. Assessments of the risks and benefits of chemoprevention are aided by the
      availability of models that can be used to estimate of the risk-benefit ratio.
      However, many physicians remain unaware of these resources to determine patient
      eligibility for chemoprevention and lack the time to provide informed counseling
      to their patients. The barriers for patients' acceptance of chemoprevention
      treatment include fear of side effects and the perception that chemoprevention
      will not substantially lower their risk of developing breast cancer. Despite
      these challenges, there are substantial opportunities to increase the utilization
      of chemoprevention. These strategies include education, dissemination of user
      friendly risk-benefit models, and the support of research efforts focused on
      identifying biomarkers that can more accurately select women most likely to
      develop breast cancer and predict responsiveness of treatment. 

PMID- 24451715
TI  - The case for prostate cancer risk reduction by 5-alpha reductase inhibitors.
AB  - Prostate cancer remains a significant public health problem. The current approach
      with prostate-specific antigen (PSA)-based screening has questionable effects on
      prostate cancer-specific mortality but is clearly associated with overdiagnosis
      of prostate cancer, especially relatively low-risk and low-volume tumors. Methods
      to decrease overdiagnosis include alterations in screening practices and,
      potentially, the use of 5-alpha reductase inhibitors. This article reviews the
      major trials that have evaluated 5-alpha reductase inhibitors in this setting:
      the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride
      Prostate Cancer Events Trial (REDUCE). Although these trials enrolled different
      patient populations, their findings are complementary and suggest a potential
      role for these agents in prostate cancer risk reduction. Use of 5-alpha reductase
      inhibitors results in an approximate 25% reduction in the detection of prostate
      cancer, reduces diagnosis of high-grade prostatic intraepithelial neoplasia
      (PIN), and improves benign prostatic hyperplasia (BPH)-related outcomes and the
      performance of PSA as a diagnostic test for aggressive prostate cancer. Side
      effects occur in a small percentage of men and consist of decreased sexual
      function and libido as well as gynecomastia. The risk of high-grade tumor
      development while receiving these agents is uncertain. 

PMID- 24451716
TI  - Screening for Prostate Cancer with Prostate-Specific Antigen: What's the
      Evidence?
AB  - In October 2011, the U.S. Preventive Services Task Force (USPSTF, or "Task
      Force") released draft recommendations on prostate cancer screening with prostate
      specific antigen (PSA), concluding that "PSA-based screening results in small or
      no reduction in prostate cancer-specific mortality and is associated with harms
      related to subsequent evaluation and treatments, some of which may be
      unnecessary." This statement was accompanied by a grade "D" recommendation, which
      indicates that in the Task Force's judgment there "is moderate or high certainty
      that the service has no net benefit or that the harms outweigh the benefits." The
      Task Force, an independent panel of nonfederal (U.S.) experts in prevention and
      evidence-based medicine, conducts systematic evidence reviews of preventive
      health care services and makes recommendations about preventive services in
      primary care. Task Force recommendations do not set U.S. federal policy but can
      and do influence reimbursement and clinical practice. In this article, we will
      present evidence the Task Force considered when making its decision, including
      two highly influential randomized controlled trials (RCTs) of prostate cancer
      screening, the European Randomized Study of Prostate Cancer (ERSPC) and the
      Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The two
      trials arrived at different conclusions about the efficacy of routine prostate
      cancer screening, but similar conclusions about the accompaniment of clinically
      relevant harms with prostate cancer screening, including overdiagnosis (screen
      detection of cancers that never would be diagnosed in the absence of screening).
      We also will present other available evidence on benefits and harms of PSA-based
      screening and consider that evidence and the findings of ERSPC and PLCO in
      conjunction with one another. 

PMID- 24451717
TI  - Glioblastoma: biology, genetics, and behavior.
AB  - Glioblastoma (GBM) is a highly malignant, rapidly progressive astrocytoma that is
      distinguished pathologically from lower-grade tumors by necrosis and
      microvascular hyperplasia. The global pattern of growth changes dramatically with
      the development of GBM histology and is characterized by hypoxia-driven
      peripheral expansion from a growing necrotic core. Necrotic foci present
      centrally in GBM and are typically surrounded by "pseudopalisading" cells-a
      configuration that is relatively unique and long recognized as an ominous
      prognostic feature. Theses pseudopalisades are severely hypoxic, overexpress
      hypoxia inducible factor-1 (HIF-1), and secrete proangiogenic factors, such as
      vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The
      microvascular hyperplasia that emerges in response promotes peripheral tumor
      expansion. Recent evidence suggests that pseudopalisades represent a wave of
      tumor cells actively migrating away from central hypoxia that arises following a
      vascular insult. Vaso-occlusive and prothrombotic mechanisms in GBM could readily
      explain the presence of pseudopalisading necrosis in tissue sections, the rapid
      peripheral expansion on neuroimaging, and the dramatic shift to an accelerated
      rate of clinical progression as a result of hypoxia-induced angiogenesis. The
      genetic alterations that coincide with progression to GBM include amplification
      of epidermal growth factor receptor (EGFR), deletion of CDKN2A, and mutation or
      deletion of PTEN. Other diagnostic and prognostic tests used in neuro-oncology
      include assessment of 1p/19q, MGMT promoter methylation, IDH1, and p53. More
      recently, the Cancer Genome Atlas data have indicated that there are four robust
      transcriptional classes of GBM, referred to as proneural, neural, classical, and
      mesenchymal. These classes have genetic associations and may pave the road for
      future development of targeted therapies. 

PMID- 24451718
TI  - Future directions in glioblastoma therapy.
AB  - The standard of care for both newly diagnosed and recurrent glioblastoma (GBM)
      patients has changed significantly in the past 10 years. Surgery followed by
      radiation and concurrent and adjuvant temozolomide is now the well-established
      standard treatment for newly diagnosed GBM. More recently, bevacizumab has become
      a mainstay of treatment for recurrent GBM. However, despite these advances and
      significant improvements in patient outcomes, the management and treatment of GBM
      patients remains a challenging and frustrating endeavor. Difficulties in
      interpretation of imaging changes after initial treatment, as well as the effects
      of antiangiogenic agents like bevacizumab on MRI characteristics, can make even
      the determination of disease progression complicated in multiple situations.
      Although a high percentage of patients benefit from antiangiogenic therapy in
      terms of radiographic response and progression-free survival, the effects of
      bevacizumab on prolonging overall survival remain controversial. Furthermore,
      tumor progression after treatment with antiangiogenic agents carries a
      particularly poor prognosis and there is a general lack of effective therapies
      for this group of patients. These limitations in terms of standard treatments
      contrast with a relative wealth of new information regarding the molecular
      underpinnings of GBM. Data from several large-scale efforts to molecularly
      profile GBM tumors including The Cancer Genome Atlas (TCGA) project have helped
      define specific molecular subtypes of GBM with distinct biology and clinical
      outcomes. These findings are helping to refine our understanding of the molecular
      heterogeneity and pathogenesis of these tumors and provide a basis for the future
      development of rational and targeted therapies for specific tumor subtypes. 

PMID- 24451719
TI  - Establishing the standard of care for patients with newly diagnosed and recurrent
      glioblastoma.
AB  - The current standard of care for patients with newly diagnosed glioblastoma
      includes maximal safe tumor resection followed by concurrent external-beam
      radiation with daily low-dose temozolomide followed by 6 to 12 months of adjuvant
      temozolomide, typically by using a cycle of 5 consecutive days out of 28. Efforts
      to improve on these results from the European Organisation for Research and
      Treatment of Cancer (EORTC)/National Cancer Institute of Canada (NCIC) trial
      using either dose-dense chemotherapy strategies or combinations with signal
      transduction modulators have, to date, been unsuccessful. Two large international
      randomized trials examining the efficacy of adding bevacizumab, an antiangiogenic
      agent, to the standard treatment have been completed, with expectations of
      results within in the next 2 years. For recurrent glioblastoma, there are no
      firmly established standards of care. Although intracavitary insertion of
      carmustine-impregnated polymers has been approved by the U.S. Food and Drug
      Administration (FDA), this strategy is not widely used. Bevacizumab has been FDA
      approved for recurrent glioblastoma, but no randomized trial has clearly
      demonstrated a survival benefit. Alternative dosing schedules of temozolomide
      (i.e., metronomic) has modest activity even in patients with prior temozolomide
      exposure. Clinical trials testing small-molecule signal transduction modulators
      have been disappointing, although most report a small response rate, suggesting
      that molecularly definable tumor subpopulations may help guide treatment
      decisions. Successful implementation of marker-based treatment would lead to
      personalized care and the creation of individualized standards of care. 

PMID- 24451720
TI  - Current concepts in brain tumor imaging.
AB  - Magnetic resonance imaging (MRI) is the most useful imaging tool in the
      evaluation of patients with brain tumors. Most information is supplied by
      standard anatomic images that were developed in the 1980s and 1990s. More
      recently, functional imaging including diffusion and perfusion MRI has been
      investigated as a way to generate predictive and prognostic biomarkers for high
      grade glioma evaluation, but additional research is needed to establish the added
      benefits of these indices to standard MRI. Response critieria for high-grade
      gliomas have recently been updated by the Response Assessment in Neuro-Oncology
      (RANO) working group. The new criteria account for nonenhancing tumor in addition
      to the contrast-enhancing abnormalities on which older criteria relied. This
      issue has recently come to the fore with the introduction of the antiangiogenic
      agent bevacizumab into standard treatment for recurrent glioblastoma. Because of
      its potent antipermeability effect, contrast enhancement is markedly reduced in
      patients who receive bevacizumab. The RANO criteria also address the phenomenon
      of pseudoprogression, in which there may be transient MRI worsening of a
      glioblastoma following concurrent radiotherapy and temozolomide. 

PMID- 24451721
TI  - Noninvasive application of alternating electric fields in glioblastoma: a fourth
      cancer treatment modality.
AB  - Tumor treating fields (TTF) therapy is a novel antimitotic, electric field-based
      treatment for cancer. This nonchemical, nonablative treatment is unlike any of
      the established cancer treatment modalities, such as surgery, radiation, and
      chemotherapy. Recently, it has entered clinical use after a decade of intensive
      translational research. TTF therapy is delivered to patients by a portable,
      battery-operated, medical device using noninvasive transducer arrays placed on
      the skin surface surrounding the treated tumor. TTF therapy is now a U.S. Food
      and Drug Administration (FDA)-approved treatment for patients with recurrent
      glioblastoma (GBM) who have exhausted surgical and radiation treatments. This
      article will introduce the basic science behind TTF therapy, its mechanism of
      action, the preclinical findings that led to its clinical testing, and the
      clinical safety and efficacy data available to date, as well as offer future
      research directions on this novel treatment modality for cancer. 

PMID- 24451722
TI  - Limitations of adaptive clinical trials.
AB  - Adaptive designs are aimed at introducing flexibility in clinical research by
      allowing important characteristics of a trial to be adapted during the course of
      the trial based on data coming from the trial itself. Adaptive designs can be
      used in all phases of clinical research, from phase I to phase III. They tend to
      be especially useful in early development, when the paucity of prior data makes
      their flexibility a key benefit. The need for adaptive designs lessened as new
      treatments progress to later phases of development, when emphasis shifts to
      confirmation of hypotheses using fully prespecified, well-controlled designs. 

PMID- 24451723
TI  - Capturing the patient perspective: patient-reported outcomes as clinical trial
      endpoints.
AB  - Just as clinical trial design and rigor have evolved with improvements in methods
      and processes, so too have methods for capturing patient data in clinical trials.
      Substantial evidence suggests that standard physician reporting of symptoms for
      which we lack objective diagnostics (e.g., pain) is often discordant with patient
      self-report. Current reporting using the National Cancer Institute Common
      Terminology Criteria for Adverse Events (CTC[AE]) for symptom capture relies on a
      filtering system, from patient to physician to medical record to medical record
      abstraction to data entry, with each step requiring interpretation and the
      possibility of error. In contrast, patient-reported outcomes (PROs) eliminate the
      filter and rely on direct report. Furthermore, the lack of validation and
      training in use of the CTC(AE) creates an inadequate data capture system.
      Inadequacies might be observed as underreporting or overreporting symptom
      prevalence and severity compared with patient self-report. Inaccuracies in
      symptom reporting can lead to missing important prognostic information, lack of
      understanding of patient adherence with therapies, and lack of information for
      patient decision making. They can also lead to opportunities lost in terms of
      labeling claims and comparative effectiveness analyses. New developments in
      patient-reported outcome (PRO) reporting, including the PRO-CTC(AE) and models
      for incorporation of PROs in clinical trials, might facilitate routine PRO
      reporting complementary to CTC(AE) in clinical trials. In addition, the cadre of
      validated PRO instruments already in existence allows for more in-depth,
      hypothesis-driven evaluations. For standard toxicity reporting, the time has come
      for mandatory routine PRO symptom reporting complementary to the CTC(AE). 

PMID- 24451724
TI  - The new national cancer institute national clinical trials network.
AB  - The National Cancer Institute (NCI) Cooperative Group Program has been reviewed
      by three published studies in the last 7 years evaluating the efficiency and
      effectiveness of this national oncology clinical trials system. The
      recommendations for improvement from these reports have prompted NCI to transform
      the Cooperative Group Program into a new NCI National Clinical Trials Network
      (NCTN) to improve the efficiency of large clinical trials and increase the speed
      of cancer translational research. The new NCTN offers community-based clinical
      investigators new opportunities to advance cancer research in their community
      setting but also presents challenges in promoting community-based research. 

PMID- 24451725
TI  - Successful Integration of Cooperative Groups: The Origin of the Children's
      Oncology Group.
AB  - In March 2000, the four legacy pediatric cooperative groups officially merged to
      become the Children's Oncology Group (COG). This was accomplished by the
      ratification of a new constitution by the respective executive committees and
      voting membership of the four legacy groups. The actual merger was preceded by a
      12 to 18 month period of planning, negotiation, and transition, overseen by a
      Transition Committee of select executive leadership under the direction of the
      four current chairs of the existing pediatric groups. Despite the constant threat
      of budget reductions and questions related to the judicious use of National
      Cancer Institute (NCI) funds to support four pediatric groups when "children
      constitute only 3% of the US cancer problem," the decision to unify was initiated
      and driven internally. The merger was envisioned as an opportunity to create
      efficiency by reducing duplicative systems and processes, which was becoming
      increasingly apparent as more planned clinical trials required intergroup
      collaboration. It was also recognized that such intergroup efforts would become
      more of a reality as clinical trial paradigms were built on risk-adjusted
      approaches. Clinically, biologically, and molecularly defined homogeneous
      subgroups of patients were of insufficient sample size within each group to
      design and conduct studies within a reasonable time frame. In essence, this
      merger was motivated by an overwhelming sense of necessity to preserve our
      mission of defining and delivering compassionate and state-of-the-art care
      through scientific discovery. The merger process itself was challenging, time
      consuming, not supported by any supplemental funding, and at times painful. What
      has emerged as a result is the largest pediatric cancer research organization in
      the world. Accomplishments in epidemiology, biology, translational science, and
      improved clinical outcomes for some pediatric cancers would have never been
      achieved without the merger. The very fact that outcome improvements were not
      realized in every type of pediatric cancer is testimony to the commitment of the
      COG membership to continue to look and move forward. 

PMID- 24451726
TI  - A critical review of the enrollment of black patients in cancer clinical trials.
AB  - Although clinical trials represent a vital opportunity for improvements in cancer
      treatment, data show that a small proportion of patients with newly diagnosed
      cancer participate in clinical research. Black patients continue to have a worse
      prognosis for most cancers compared with other patients of other
      races/ethnicities. Racial/ethnic- and age-related disparities in clinical trial
      accrual are also well documented. The recruitment and retention of minorities in
      these trials present an even greater challenge despite regulatory efforts and
      initiatives to increase representation. Treatment data from homogenous
      populations prevent us from understanding therapeutic response and the true
      safety profile of novel therapies. Patient-, physician-, and system-level factors
      that affect trial participation have been extensively studied. However, years of
      accrual data remain largely unchanged, suggesting the challenge lies in
      effectively addressing these factors. Furthermore, data showing that black
      patients tend to have more advanced stage cancers at the time of diagnosis in
      fact beg their overrepresentation on clinical trials. An inability to
      successfully enroll diverse populations in clinical trials only exacerbates
      racial/ethnic differences in cancer treatment and survivorship. 

PMID- 24451727
TI  - Trastuzumab Emtansine (T-DM1): Hitching a Ride on a Therapeutic Antibody.
AB  - The treatment of cancers with chemotherapy is frequently limited by side effects.
      The effectiveness may be improved by the use of monoclonal antibodies to deliver
      cytotoxic agents to cancer cells while limiting exposure to normal tissues. The
      use of antibody-drug conjugates (ADCs) is one such strategy: a drug connected by
      a linker to an antibody specific for a tumor antigen is the basic makeup of an
      ADC. Overexpression and amplification of HER2 is associated with clinically
      aggressive breast cancers, and the use of trastuzumab to target HER2 has been
      highly effective. That said, most patients with HER2-positive metastatic breast
      cancer will eventually have disease progression during targeted therapy.
      Trastuzumab emtansine (T-DM1) is a novel ADC that combines the humanized antibody
      trastuzumab and the potent antimicrotubule agent T-DM1 (derivative of maytansine)
      using a unique and highly stable linker. The potential of maytansine was found in
      the 1970s with clinical responses noted against breast cancer; however,
      substantial toxicity prohibited further development. DM1 possesses in vitro
      cytotoxicity 10 to 200 times greater than that of taxanes and vinca alkaloids. A
      phase I trial of T-DM1 for patients with heavily pretreated HER2-positive breast
      cancer determined a recommended dose of 3.6 mg per kilogram delivered every 3
      weeks. Responses were seen in multiple patients. T-DM1 was then studied in phase
      II trials of patients with HER2-positive metastatic breast cancer. In a studies
      of 112 and 110 patients in whom disease had progressed during HER2-directed
      therapy, T-DM1 was associated with objective response rates of 26% and 34%,
      respectively. The agent was well tolerated in both trials, with most toxicities
      being grade 1 and 2, and no bleeding episodes or cardiac events occurring.
      Additional phase II and III trials are now evaluating T-DM1 in the first-line
      setting. In one such trial, T-DM1 was compared with standard dosing of
      trastuzumab every 3 weeks plus docetaxel every 3 weeks. Objective response rates
      were comparable and grade 3 or4 adverse events were substantially reduced in the
      T-DM1 arm. The anticipated selective activity and reduction in side effects were
      thus noted. Randomized multicenter phase III trials are ongoing, including the
      EMILIA trial, an open-label trial of T-DM1 compared with the U.S. Food & Drug
      Administration-approved regimen of capecitabine plus lapatinib. The results of
      studies completed to date suggest T-DM1 is active in patients who have cancer
      resistant to trastuzumab-based combinations. 

PMID- 24451728
TI  - Targeting CD30 in hodgkin lymphoma: antibody-drug conjugates make a difference.
AB  - CD30 expression is characteristic of the malignant Reed-Sternberg cell in Hodgkin
      lymphoma (HL) and several other lymphoid malignancies, such as anaplastic large
      cell lymphoma (ALCL). Although unconjugated anti-CD30 antibodies have had minimal
      therapeutic activity in patients with HL as single agents, the CD30-directed
      antibody-drug conjugate (ADC) brentuximab vedotin has demonstrated activity that
      has resulted in its recent regulatory approval for the treatment of patients with
      relapsed HL and ALCL. Approximately 75% of patients with recurrent HL achieve
      objective responses, with the principal toxicity being peripheral neuropathy.
      Ongoing studies are evaluating treatment with this agent as part of first-line
      therapy, for patients with relapsed disease, and for patients with resistant
      disease and limited other options. Brentuximab vedotin demonstrates the
      therapeutic value of antibody-drug conjugation and serves as a model of how a
      novel, targeted approach can be employed to potentially further improve outcomes
      in settings where curative chemotherapeutic regimens are already available. 

PMID- 24451729
TI  - Drug development in the era of personalized oncology: from population-based
      trials to enrichment and prescreening strategies.
AB  - Recent advances in tumor biology and human genetics along with the development of
      drugs for specific targets hold promise for an era of personalized oncology
      treatment. Routine use of modern technologies, such as large-scale genome
      sequencing, will help to unravel the specific biology of each tumor. Adding a
      rigorous genomic view could determine key genetic events, critical dependencies,
      and stratification of patients in early clinical trials. Integrating biomarker
      development into the early testing of novel agents might provide clinically
      relevant therapeutic opportunities for patients with advanced-stage cancer and
      also accelerate the drug-approval process. After recent success stories of
      therapies targeting driver molecular aberrations in genetically defined tumor
      subtypes, innovative clinical trials based on a strong biologic hypothesis are
      expected to bring further excitement to the field. In this article, we describe a
      new trend in biomarker-driven early drug development using enrichment and
      prescreening strategies. Technical and logistical obstacles that may hinder
      progress of this approach will be discussed, along with ethical and economic
      concerns. 

PMID- 24451730
TI  - Practical management of immune-related adverse events from immune checkpoint
      protein antibodies for the oncologist.
AB  - Monoclonal antibodies directed against immune checkpoint proteins, such as
      cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1), can boost
      endogenous immune responses directed against tumor cells. Recently, ipilimumab
      was approved by the U.S. Food and Drug Administration (FDA) for the treatment of
      metastatic melanoma, and the anti-PD-1 antibody BMS-936558 has shown promising
      results in patients with melanoma, non-small cell lung cancer, and renal cell
      cancer. During treatment with these antibodies, a unique set of toxicities occur
      called immune-related adverse events (irAEs). These irAEs may occur at any time
      during treatment and include colitis characterized by a mild to moderate but
      occasionally severe and persistent diarrhea. Hypophysitis, hepatitis,
      pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have
      also been reported with ipilimumab, and a subset of those side effects has also
      been observed with BMS-936558. Patient and physician education as well as good
      patient-caretaker communication are keys to limiting the morbidity of irAEs.
      Early recognition of these irAEs and initiation of treatment are critical to
      reduce the risk of complications, since virtually all irAEs are reversible with
      the use of steroids and other immune suppressants. The onset of grade 3 to 4
      irAEs correlated with treatment response in some ipilimumab studies. This article
      provides detailed description and recommendations for practicing oncologists to
      manage the common irAEs associated with antibodies against immune checkpoint
      blockade. 

PMID- 24451731
TI  - Treatment of chronic myelogenous leukemia as a paradigm for solid tumors: how
      targeted agents in newly diagnosed disease transformed outcomes.
AB  - Although chronic myelogenous leukemia (CML) is rare, with approximately 5000 new
      cases in the United States annually, it may be the poster child for the future of
      oncology. Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor (TKI),
      transformed the course of CML from a rapidly fatal disease (median survival, 3 to
      6 years) to a functionally curable, indolent disease with an estimated median
      survival of more than 25 years. This transformation can be attributed to several
      key factors: the identification of a causal and actionable molecular aberration
      BCR-ABL; the development of a potent and selective Bcr-Abl TKI-imatinib; and,
      importantly the application of imatinib in the earliest phase of CML. In
      contrast, imatinib, if used in CML blastic phase, improves median survival to
      only about 1 year. Similar to CML blastic phase, metastatic solid malignancies
      have undergone genetic evolution, and their molecular aberrations are complex. As
      a result, resistance is common and eradication is difficult. The key to the
      dramatic improvement in the survival of patients with CML involved using imatinib
      in newly diagnosed disease, before blastic transformation. We hypothesize that
      metastatic solid tumors are analogous to CML blastic phase, and that to achieve
      improvements in solid tumor outcomes similar to those seen in CML, application of
      targeted agents to newly diagnosed disease may be required to prevent disease
      transformation (i.e., metastases). Targeting driver mutations at the time of
      diagnosis may be critical to the goal of markedly changing the outlook for
      patients with cancer. 

PMID- 24451732
TI  - Targeting Molecular Aberrations in Breast Cancer: Is It about Time?
AB  - Breast cancer is not one homogeneous disease; it is a heterogeneous cancer with
      remarkable genomic variation and variable risk for systemic spread, time to
      recurrence, and response to treatment. Although it is increasingly clear that a
      substantial proportion of newly diagnosed patients with breast cancer carry only
      minimal risk of developing metastatic disease, our inability to accurately
      prognosticate leads to systemic overtreatment. The recent introduction of
      multigene predictors for baseline risk assessment and treatment response in
      breast cancer subsets heralds the beginning of personalized cancer care and the
      transition to precision medicine. At the same time, rapid clinical adoption of
      these predictors illustrates the voracious unmet need for better and more finely
      tuned prognostic and predictive tools. Recent advances in clinical trial designs
      have enabled the testing of novel agents in combination with standard therapy in
      the neoadjuvant setting, with a goal of identifying the specific biomarker-drug
      pairs that should be advanced for confirmatory trials and accelerated approval on
      the basis of response to therapy. 

PMID- 24451733
TI  - Is there currently an established role for the use of predictive or prognostic
      molecular markers in the management of colorectal cancer? A point/counterpoint.
AB  - The term "personalized oncology" means different things to the oncologist than to
      the patient. But fundamentally, the phrase creates the expectation that decisions
      can be informed by the unique features of the patient and patient's cancer. Much
      like determining antibiotic sensitivities in urinary tract infections, the
      oncologist is expected to choose the right treatment(s), for each individual
      patient. Numerous methods can be used to "personalize" management decisions,
      although truly useful biomarkers continue to escape our grasp. Positron Emission
      Tomography in patients with GI stromal tumors or genotyping of c-kit in chronic
      myelogenous leukemia cells can guide the use of imatinib, these scenarios
      represent a minority of patients. The promise of individualized therapy, however,
      has led to the commercialization of numerous assays to probe patient's genetic
      make-up and that of the tumor. Breast cancer management has benefitted from the
      analysis of gene recurrence scores. More recently the analysis of germline or
      tumor-associated mutations in non-small cell lung cancer and melanoma has led to
      clinically meaningful molecular subsets of these diseases, guiding the successful
      targeting of such cancers with small-molecule inhibitors. Despite the high
      incidence of colorectal cancer and our relatively long-standing grasp of the
      molecular pathways in colorectal carcinogenesis, the management of these patients
      remains mostly empiric and movement toward "personalization" has been slow and
      incremental. Now, however, molecular imaging and commercial assays for genetic
      makeup of tumor specimens has put the oncologist and oncologic surgeon in the
      crossfire with patients and families who believe the era of "personalization" is
      here. 

PMID- 24451734
TI  - The interventional radiologist role in treating liver metastases for colorectal
      cancer.
AB  - Interventional radiologists (IRs) have an expanding role in the treatment of
      liver metastases from colorectal cancer. Increasing data on the ability to treat
      liver metastases with locoregional therapies has solidified this position.
      Ablative approaches, such as radiofrequency ablation and microwave ablation, have
      shown durable eradication of tumors. Catheter-directed therapies-such as
      transarterial chemoembolization (TACE), drug-eluting beads (DEB), Y90
      radioembolization, intra-arterial chemotherapy ports, and isolated hepatic
      perfusion (IHP)-are potential techniques for managing patients with unresectable
      liver metastases. Understanding the timing and role of these techniques in the
      multidisciplinary care of the patient is critical. Implementation of the IR
      clinic for consultation has enabled better integration of these therapies into
      the patient's overall care and has facilitated improved opportunities for
      clinical studies. 

PMID- 24451735
TI  - Curative-Intent Treatment for Colorectal Liver Metastases: A Medical Oncologist's
      Perspective.
AB  - Resection or ablation of CRC liver metastases can be offered with curative intent
      in some, but not all patients in whom resection is technically possible.
      Chemotherapy can improve the potential for cure to some degree, either in the
      adjuvant or neoadjuvant setting, or, in relatively rare circumstances, by
      converting truly unresectable disease into resectable. Careful and realistic
      patient selection, with an individualized and realistic assessment of curative
      potential, is key to providing each patient with the means to make realistic
      treatment choices. 

PMID- 24451736
TI  - Surgical treatment of colorectal cancer liver metastases.
AB  - Treatment strategies for patients with stage IV colorectal cancer have changed
      markedly in the last decade. Patients with colorectal cancer metastases to the
      liver have always been a fascinating group to consider biologically and for local
      regional treatment strategies. In the late 1980s through the 1990s, resection was
      performed for a select subset of patients who had resectable disease. However, a
      high proportion of patients had bilobar unresectable disease and were treated
      with either 5-fluorouracil-based systemic chemotherapy or implanted hepatic
      arterial infusion pumps. The advent of the new millennium was associated with the
      availability of several new cytotoxic and biologic agents active in colorectal
      cancer. These agents have completely changed the approach to the treatment of
      patients with colorectal cancer liver metastases and thus have increased the
      complexity of the decision-making process for treatment of these patients. 

PMID- 24451737
TI  - Minimally invasive surgery of rectal cancer: current evidence and options.
AB  - Minimally invasive surgery (MIS) of colorectal cancer has become more popular in
      the past two decades. Laparoscopic colectomy has been accepted as an alternative
      standard approach in colon cancer, with comparable oncologic outcomes and several
      better short-term outcomes compared to open surgery. Unlike the treatment for
      colon cancer, however, the minimally invasive approach in rectal cancer has not
      been established. In this article, we summarize the current status of MIS for
      rectal cancer and explore the various technical options. 

PMID- 24451738
TI  - Radiation in rectal cancer: what are the options and if/when can it be avoided?
AB  - Treatment of rectal cancer has improved greatly over recent decades. This review
      looks at the pivotal trials in the development of the current standard of therapy
      as well as new directions for more individualized therapy for rectal cancer.
      Rates of local recurrence and overall survival (OS) for surgery alone have
      improved with the use of (neo)adjuvant 5-fluorouracil (5-FU)-based
      chemoradiation. New surgical techniques have improved outcomes, but preoperative
      radiotherapy still confers an additional benefit. Despite benefits in the
      metastatic setting, the addition of oxaliplatin to 5-FU and radiotherapy has not
      shown improved outcomes, although it increased toxicity. Preoperative therapy
      also allows for the identification of predictive and prognostic markers for
      response to treatment, which has great potential to individualize treatment.
      Currently, the search for validated biomarkers and the refinement of risk
      stratification are the focus of ongoing study. Tailored therapy may include
      modification of the pelvic radiotherapy field, nonoperative therapy, or avoidance
      of radiotherapy. 

PMID- 24451739
TI  - Stage III Colon Cancer: What Works, What Doesn't and Why, and What's Next.
AB  - Adjuvant treatment for patients with stage III colon cancer, one of the most
      common malignancies, is an important issue in oncology. The use of adjuvant
      chemotherapy in this setting has undoubtedly improved prognosis. This article
      describes the development of adjuvant therapy and progress in the past decade as
      well as failures in multiple agents that have demonstrated efficacy in the
      metastatic setting. Finally, the current clinical trials will be reviewed, as
      well as complementary therapies including diet and exercise for survivors of
      colorectal cancer. 

PMID- 24451740
TI  - A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context.
AB  - Since 1996, the cornerstone of chemotherapy for advanced pancreatic cancer has
      been gemcitabine, which has a genuine, but modest effect on survival and quality
      of life. It has been remarkably difficult to improve on these outcomes. Many
      phase III studies of gemcitabine doublets have been uniformly negative, with the
      exception of a trial of gemctabine plus erlotinib, which provided only marginal
      benefit. In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil,
      irinotecan, and oxaliplatin) emerged as a major treatment advance for patients
      with metastatic pancreatic cancer. In a trial with 342 patients, FOLFIRINOX
      yielded a longer median overall survival (11.1 vs. 6.8 months, hazard ratio [HR]
      0.57, p < 0.001), a superior progression-free survival (6.4 vs. 3.3 months, HR
      0.47, p < 0.001), a higher objective response rate (31.6% vs. 9.4%, p < 0.001),
      and a significant increase in time until definitive deterioration in quality of
      life, compared with gemcitabine. FOLFIRINOX is also more cost-effective than
      gemcitabine. Because of higher rates of grade 3 to 4 neutropenia (46% vs. 21%),
      febrile neutropenia (5% vs. 1%), and diarrhea (13% vs. 2%) with FOLFIRINOX,
      vigilant patient selection, education, and monitoring are essential.
      Retrospective single-institution series confirm the substantial activity of
      FOLFIRINOX in metastatic, locally advanced, and previously-treated patients;
      demonstrate its safety in individuals with biliary stents; and elucidate how
      physicians routinely modify drug doses without clear evidence or guidelines.
      Ongoing and planned studies will prospectively evaluate FOLFIRINOX in the
      adjuvant, locally advanced, and borderline resectable settings, will add targeted
      agents to FOLFIRINOX, and will evaluate how to adjust doses to ameliorate
      toxicity. 

PMID- 24451741
TI  - A matter of timing: is there a role for radiation in locally advanced pancreatic
      cancer, and if so, when?
AB  - The role of radiation therapy in the management of locally advanced pancreatic
      cancer is controversial. Despite its localized presentation, locally advanced
      pancreatic cancer is characterized by high rates of metastases. Historic data
      have been mixed, and newer studies have called into question the use of radiation
      therapy. However, it appears that patients more likely to benefit from
      chemoradiation can be identified with an induction phase of chemotherapy. Data
      evaluating this approach suggest that approximately 30% of patients will develop
      metastatic disease within the first 3 to 4 months of chemotherapy. Patients
      without progression who receive chemoradiation therapy may experience improved
      survival. Future directions include the validation of this strategy and the
      integration of biologic agents. 

PMID- 24451742
TI  - A myriad of symptoms: new approaches to optimizing palliative care of patients
      with advanced pancreatic cancer.
AB  - Patients with advanced pancreatic cancer (APC) require early and frequent
      palliative interventions to achieve optimal quality of life for the duration of
      illness. Evidence-based supportive treatments exist to maximize quality of life
      for any patient, whether receiving chemotherapy or not. This article provides a
      comprehensive review of symptoms with current treatment recommendations and
      directions for future development. Celiac plexus neurolysis improves pain in the
      majority of patients with APC and should be moved earlier in the analgesic
      paradigm. Malignant bowel obstruction can be palliated quickly with optimal
      management via gastric decompression, octreotide, parenteral opioids, and
      standing antiemetics. Recommendations are provided for best treatment of
      malignant gastroparesis, gastric outlet obstruction, and chemotherapy-induced
      nausea and vomiting in this population. Malignant ascites can be treated
      initially with diuretics and sodium-restriction in patients with an exudative
      process; however, an indwelling catheter is recommended for patients with
      recurrent ascites, particularly because of carcinomatosis or a refractory
      process. With exocrine insufficiency contributing to weight loss, pancreatic
      enzyme replacement is essential to improve nourishment in the majority of
      patients. Presently, megestrol acetate is the only U.S. Food and Drug
      Administration (FDA)-approved therapy for the anorexia-cachexia syndrome,
      although future developments are promising. Finally, patients with advanced
      pancreatic cancer should be screened and treated early for depression as a common
      comorbid diagnosis. Early palliative care consultation also helps address the
      existential and psychosocial concerns of patients facing death from pancreatic
      cancer in a holistic manner. 

PMID- 24451743
TI  - Varying lymphadenectomies for gastric adenocarcinoma in the East compared with
      the west: effect on outcomes.
AB  - There are notable differences in surgical approaches to gastric adenocarcinoma
      throughout the world, particularly in terms of the extent of lymphadenectomy
      (LAD). In high-incidence countries such as Japan and South Korea, more extensive
      (e.g., D2) lymphadenectomies are standard, and these surgeries are generally done
      by experienced surgeons with low morbidity and mortality. In countries such as
      the United States, where the incidence of gastric adenocarcinoma is 10-fold
      lower, the majority of patients are treated at nonreferral centers with less
      extensive (e.g., D1 or D0) lymphadenectomy. There is little disagreement among
      gastric cancer (GC) experts that the minimum lymphadenectomy that should be
      performed for gastric adenocarcinoma should be at least a D1 lymphadenectomy, and
      many of these experts recommend a D2 lymphadenectomy. More extensive
      lymphadenectomies provide better staging of patient disease and likely reduce
      locoregional recurrence rates. Two large, prospective randomized trials performed
      in the United Kingdom and the Netherlands in the 1990s failed to demonstrate a
      survival benefit of D2 over D1 lymphadenectomy, but these trials have been
      criticized for inadequate surgical training and high surgical morbidity and
      mortality rates (10% to 13%) in the D2 group. More recent studies have
      demonstrated that Western surgeons can be trained to perform D2 lymphadenectomies
      on Western patients with low morbidity and mortality. The 15-year follow-up of
      the Netherlands trial now demonstrates an improved disease-specific survival and
      locoregional recurrence in the D2 group. Retrospective analyses and one
      prospective, randomized trial suggest that there may be a survival benefit to
      more extensive lymphadenectomies when performed safely, but this assertion
      requires further validation. 

PMID- 24451744
TI  - Will disease heterogeneity help define treatment paradigms for gastroesophageal
      adenocarcinoma? A global perspective.
AB  - Cancers of the upper gastrointestinal (GI) tract form a heterogeneous group of
      diseases for which treatment paradigms for localized disease continue to emerge.
      Recently, several phase III studies in esophagus and gastric cancer that have
      attempted to define new standards of care have been reported. However,
      controversy still persists and treatment algorithms often depend on individual
      preference, patient referral patterns, and treatment biases. In the current era
      of improving quality control and standardization of care, such variations in
      practice present a substantial challenge for both patients and physicians. In
      this article, I will highlight differences in disease biology for upper GI
      diseases, and in particular, gastric cancer. 

PMID- 24451745
TI  - Stereotactic body radiation therapy for hepatocellular carcinoma.
AB  - Stereotactic body radiotherapy (SBRT), in which highly conformal potent radiation
      doses are delivered in fewer fractions than traditional radiation therapy (RT),
      is an increasingly popular treatment for hepatocellular carcinoma (HCC). The
      great majority of HCCs smaller than 6 cm and with Child-Pugh A liver function are
      controlled with SBRT with limited toxicity. Long-term local control is reduced in
      larger tumors, and toxicity is increased in patients with Child-Pugh B or C liver
      function. SBRT is an effective treatment for tumor vascular thrombi and can lead
      to sustained vascular recanalization. The first site of recurrence following SBRT
      is most often within the liver, away from the high dose volume, providing
      rationale for combining SBRT with regional or systemic therapies. Randomized
      trials of SBRT are warranted. 

PMID- 24451746
TI  - Patient selection, resection, and outcomes for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an aggressive malignancy of the liver that most
      often arises in patients with cirrhosis and other chronic liver diseases.
      Worldwide, it is the sixth most common cancer and the third most common cause of
      cancer-related death. Median survival is poor, ranging from 6 to 20 months.
      Definitive treatment options for HCC are surgical resection, ablation, or
      transplantation. The selection of patients for surgical resection is based on
      clinical findings, laboratory data, and imaging. Although a number of staging
      systems exist, all have their limitations. A multidisciplinary approach to
      patient selection for surgery that includes the input of an experienced liver
      surgeon assures optimal outcomes. Sound understanding of liver segmentation,
      modern surgical techniques, and the use of intraoperative ultrasound have led to
      a reported perioperative mortality rate below 3%, blood transfusion requirements
      of less than 10%, and 5-year survival rates of at least 50%. Advances in
      laparoscopic technique and technology have expanded the indications for a safe
      and oncologically appropriate minimally invasive resection. Deciding which
      treatment option to employ depends on tumor resectability and the degree of
      underlying liver disease, which is present in 80% to 85% of patients with HCC;
      however, despite these surgical advances, a high recurrence rate of 70% in
      patients with cirrhosis and a survival rate of 65% to 80% in well-selected
      transplant patients are expected. This article will focus on the evaluation and
      selection of patients for surgical intervention, considerations in selecting the
      appropriate type of resection, and expected outcomes following liver resection. 

PMID- 24451747
TI  - A renaissance in therapeutic options for pancreatic neuroendocrine tumors.
AB  - The field of pancreatic neuroendocrine tumors (NETs) has seen a remarkable
      renaissance in recent years with exponential increases in published research,
      clinical trials, and U.S. Food and Drug Administration (FDA)-approved treatments.
      Surgical resection remains the foundation for management of locoregional disease.
      However, for patients with advanced disease, novel therapeutic options have
      emerged. Two separate randomized placebo-controlled studies have shown prolonged
      progression-free survival (PFS) with everolimus or sunitinib. Future studies are
      designed to answer questions about the role of somatostatin analogs as
      antiproliferative agents, combinations of biologic therapies, and new cytotoxic
      chemotherapy backbones. 

PMID- 24451748
TI  - A review of the management of hepatocellular carcinoma: standard therapy and a
      look to new targets.
AB  - Management of hepatocellular carcinoma (HCC) continues to be challenging, but new
      treatment options are evolving. A multidisciplinary evaluation will help make the
      best treatment decisions for each patient. Although we continue to improve the
      outcomes of curative treatment with resection, liver transplant, and
      radiofrequency ablation (RFA), many new liver-directed regional therapies
      including drug-eluting beads, radioembolization, and radiation are emerging.
      Sorafenib remains the only approved agent for advanced HCC, and its role in the
      adjuvant setting following resection or RFA, with transarterial
      chemoembolization, or in combination with other targeted agents or chemotherapy
      in the advanced stage is under investigation. Many molecularly targeted agents
      with novel mechanisms of action are under active development. 

PMID- 24451749
TI  - Advanced biliary tract cancers.
AB  - Single-agent management of metastatic biliary tract cancers with 5-fluorouracil
      (5-FU) or gemcitabine has shown limited efficacy, although 5-FU has been shown to
      be more effective than best supportive care alone. An analysis of phase II trials
      has suggested that platinums enhanced the efficacy of single-agent
      fluoropyrimidines. In a phase III randomized trial comparing single-agent
      gemcitabine with gemcitabine plus cisplatin, the gemcitabine/cisplatin
      combination significantly improved median overall survival (OS) and progression
      free survival (PFS), which established a new option for standard of care.
      However, the future of cancer medicine lies in newer, targeted agents. In the
      management of biliary tract cancers, preliminary evidence with epidermal growth
      factor receptor inhibitors has already demonstrated activity. This article
      reviews systemic therapies for metastatic biliary tract cancers as they relate to
      current and emerging standards of care. 

PMID- 24451750
TI  - Optimal use of imaging to guide treatment decisions for kidney cancer.
AB  - Treatment monitoring for solid tumors in general and for metastatic renal cancer
      in particular has been dominated by assessment of tumor burden via cross
      sectional imaging. This poses a special problem for the mammalian target of
      rapamycin and vascular endothelial growth factor pathway-directed agents used in
      this disease. The standard RECIST metrics used to categorize "response" and
      "progression" are arbitrary and do not adequately capture the effect of these
      agents. Other approaches, including use of relative RECIST measures as a
      continuous variable, volumetric measurements, and functional assessments, such as
      dynamic contrast-enhanced magnetic resonance imaging-based quantitative variables
      and fluorodeoxyglucose-positron emission tomography, have been proposed as
      alternatives, but the data do not support their routine clinical use. Even fewer
      data are available on the use of baseline imaging characteristics to choose a
      specific therapy. Therefore, until further research on imaging predictive and
      intermediate biomarkers matures, a combination of standard cross-sectional
      imaging and clinical judgment is the most pragmatic option for treatment decision
      making for patients with metastatic renal cancer. 

PMID- 24451751
TI  - State-of-the-Art Management for the Patient with Castration-Resistant Prostate
      Cancer in 2012.
AB  - Much progress has been made in metastatic castration-resistant prostate cancer
      (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved
      survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was
      the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T,
      cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new
      agents, radium-223 and MDV-3100, have recently reported large phase III trials
      prolonging overall survival and will be submitted for regulatory approval in
      2012. One can now begin to ask, is there an optimal sequence for therapies in
      metastatic CRPC? Despite the recent progress, there is much we do not know and
      virtually no information on this important question. We know that
      abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a
      patient after receiving docetaxel, but we do not know what, if anything,
      represents the optimal sequence for abiraterone and cabazitaxel. In fact we do
      not understand how one therapy may affect the response to a subsequent therapy.
      We are also aware that the pre- and postdocetaxel spaces represent regulatory
      rather than biologic divisions. In addition, despite the proven role of
      docetaxel/prednisone, many patients with CRPC are not considered to be suitable
      for chemotherapy, and worldwide many never receive any form of chemotherapy. What
      is the optimal management for these patients? Taken together it is reasonable to
      assess patient preferences, prior therapies and response/tolerance to prior
      therapies, burden of disease, comorbidities, current symptoms, drug toxicities,
      out-of-pocket costs, etc., in clinical decision making. Given the many factors we
      do not know, it is hard to be dogmatic in approaching the therapeutic options for
      the patient with CRPC. We will likely soon move beyond the current sequencing
      paradigm and begin to assess new combinations in a systematic and rational
      fashion. Perhaps one day, in the not too distant future, we will develop
      molecular "stratification systems" to better guide therapeutic choices in CRPC. 

PMID- 24451752
TI  - Prognostic, predictive, and surrogate factors for individualizing treatment for
      men with castration-resistant prostate cancer.
AB  - With the surge in therapeutic options for castration-resistant prostate cancer
      (CRPC) comes increasingly complicated treatment decision making, highlighting the
      need for biomarkers that can identify appropriate patients for specific
      treatments and accurately assess disease response. Here we discuss existing and
      potential prognostic, predictive, and surrogate biomarkers in CRPC. 

PMID- 24451753
TI  - The evolving landscape of metastatic renal cell carcinoma.
AB  - The treatment paradigm in metastatic renal cell carcinoma (mRCC) has evolved over
      the last 5 years. There are now seven approved targeted therapies against the
      vascular endothelial growth factor (VEGF) and mammalian target of rapamycin
      (mTOR) pathways. The use of targeted therapy, sequences, combinations, and
      investigational compounds will be discussed. Prognostic and predictive tools are
      detailed, although much work must be done to find predictive biomarkers in an
      effort to individualize therapy for patients. 

PMID- 24451754
TI  - New developments in urothelial cancer.
AB  - Urothelial cancer is among the most chemotherapy-sensitive neoplasms of all the
      solid tumors. However, for the majority of patients with advanced disease,
      response durations with conventional treatment are relatively short. Second-line
      systemic treatment regimens are associated with modest response rates and poor
      outcomes. Trials in both the first- and second-line settings have demonstrated
      that a ceiling in efficacy has likely been reached with cytotoxic drugs,
      particularly in unselected patient populations. Promising areas of investigation
      include integrating predictive biomarkers to optimize patient selection for
      specific therapies, disrupting driving oncogenomic mutations, and associated
      signaling pathways and cotargeting both tumor and the immune system or tumor
      stroma. In addition, expanded sources of evidence generation are of interest in
      an effort to refine treatment for the general population of patients with
      advanced urothelial cancer, not only those who meet the narrow eligibility
      criteria used in most clinical trials. 

PMID- 24451755
TI  - New developments in prostate cancer therapy.
AB  - Prostate cancer is the most common nonskin malignant neoplasm in men worldwide.
      In the United States, 241,740 new diagnoses of prostate cancer and 28,170
      prostate cancer deaths have been estimated for 2012, representing 28% of new
      cancer cases and 10% of male cancer deaths.(1) Although metastatic prostate
      cancer remains an incurable disease, substantial advances have been made in
      therapeutic options available for men in the past several years. Development of
      novel agents that modulate the androgen receptor pathway, growth factor signaling
      pathways, and immune function and bone targeting pathways has been the focus of
      therapeutic strategies because of its significance in the biology of prostate
      cancer progression. Several of the agents have gained U.S. Food and Drug
      Administration (FDA) approval, whereas many are in late-stage clinical trials.
      With the growth of available treatment options, a major challenge as we move
      forward will be to determine the best sequence and/or combination of therapy that
      will result in maximum clinical efficacy with minimum toxicity. Highlighted in
      this publication are several of the exciting advances in prostate cancer therapy
      for patients with metastatic, castrate-resistant prostate cancer. 

PMID- 24451756
TI  - Adjuvant treatment of older patients with lung cancer.
AB  - Although advances in the molecular biology of lung cancer have rapidly impacted
      management of patients with advanced stage non-small cell lung cancer (NSCLC),
      the principal treatment in the adjuvant setting of early stage NSCLC remains
      platinum-based chemotherapy regimens. The evidence available from clinical trials
      demonstrates a similar benefit of adjuvant chemotherapy in fit, older patients as
      well as younger patients. Observational studies suggest that adjuvant
      chemotherapy for older patients provides comparable survival benefit, along with
      increased toxicity. The lower use of chemotherapy in the older population also
      suggests that the selection of appropriate patients remains an important part of
      the decision process. Carboplatin therapy may be substituted for cisplatin in
      selected older patients, and different options exist for the second cytotoxic
      chemotherapy agent. As in all patients, and particularly in this vulnerable
      population receiving cytotoxic chemotherapy, supportive care is vital. Increasing
      enrollment of the older population in clinical trials will be important to
      improve the evidence for our decision-making in the future. 

PMID- 24451757
TI  - Considerations and controversies in the management of older patients with
      advanced cancer.
AB  - The incidence of cancer increases with age. Oncologists need to be adept at
      assessing physiologic and functional capacity in older patients in order to
      provide safe and efficacious cancer treatment. Assessment of underlying health
      status is especially important for older patients with advanced cancer, for whom
      the benefits of treatment may be low and the toxicity of treatment high. The
      comprehensive geriatric assessment (CGA) is the criterion standard for evaluation
      of the older patient. The combined data from the CGA can be used to stratify
      patients into categories to better predict risk for chemotherapy toxicity as well
      as overall outcomes. The CGA can also be used to identify and follow-up on
      possible functional consequences from treatment. A variety of screening tools
      might be useful in the oncology practice setting to identify patients who may
      benefit from further testing and intervention. In this chapter, we discuss how
      the principles of geriatrics can help improve the clinical care of older adults
      with advanced cancer. Specifically, we discuss assessing tolerance for treatment,
      options for chemotherapy scheduling and dosing for older patients with advanced
      cancer, and management of under-recognized symptoms in older patients with
      cancer. 

PMID- 24451758
TI  - International perspective on the global advances in gynecologic oncology.
AB  - The treatment of gynecologic cancer has evolved over the years, with greater
      emphasis on tailored surgery and reducing morbidity and mortality related to
      surgery, particularly in the management of vulvar and cervical cancer. The
      addition of concurrent chemotherapy to radiation regimens has improved survival
      of patients with cervical cancer in developed countries; however, most women with
      cancer in developing countries have advanced, untreatable disease and minimal
      access to anticancer therapies. In the past 15 years there has been intense
      research into alternatives to cervical cytologic testing, particularly in low
      resourced regions but also in an attempt to improve on cytologic testing in
      developed countries. Surgical staging in endometrial cancer has enabled the use
      of adjuvant radiation to be individualized to the patient's particular risk
      factors for recurrence. The management of ovarian cancer, long stagnant since the
      introduction of platinum and paclitaxel as chemotherapeutic agents, is set to
      change with the onset of molecular and genetic profiling and the introduction of
      novel therapies. 

PMID- 24451759
TI  - The European society of gynaecological oncology: update on objectives and
      educational and research activities.
AB  - The European Society of Gynaecological Oncology (ESGO) is the principal European
      society contributing to the study, prevention, and treatment of gynecologic
      cancers. Founded in 1983, ESGO has more than 1,300 members in more than 40
      European countries and worldwide who benefit from ESGO's innovative education and
      research initiatives and networking opportunities. ESGO objectives have been
      recently identified through a strategic planning process and include education,
      care, research, collaboration, awareness, and sustainability. As a leading
      gynecologic oncology society, ESGO holds biennial meetings where experts meet to
      discuss latest advances in gynecologic treatment and care. The 17(th)
      International Meeting of ESGO (ESGO 17) proved to be a resounding success, with
      2,700 delegates and speakers who gathered from around the world in the cultured
      city of Milan, Italy. The structure of the congress included keynote lectures,
      debates, state-of-the art sessions, and focused sunrise sessions, together with
      oral and poster presentations and satellite symposia sponsored by pharmaceutical
      companies. For the first time, during ESGO 17 the Society organized a seminar for
      European patient groups with an interest in gynecologic cancers with the aim of
      facilitating different patientrelated activities across Europe. Moreover, The
      European Network of Young Gynaecologic Oncologists (ENYGO), the European Network
      of Gynaecologic Oncology Trial Groups (ENGOT), and the European Network of
      Translational Research in Gynaecological Oncology (ENTRIGO) had their own section
      during ESGO 17. ESGO also holds numerous workshops throughout the calendar year
      and provides clinical and research grants, online educational materials,
      webcasts, and numerous networking opportunities. 

PMID- 24451760
TI  - Biologicals in the upfront treatment of ovarian cancer: focus on bevacizumab and
      poly (adp-ribose) polymerase inhibitors.
AB  - Biologicals have made a major impact in the management of several cancers, but
      have hitherto had a negligible impact in ovarian cancer. Fortunately, ovarian
      cancer has been much more sensitive to cytotoxic chemotherapy than many cancers,
      so treatments were still available. However, improvements are required as more
      than 80% of patients who present with advanced ovarian cancer eventually will die
      as a result of their disease. The antiangiogenic antibody bevacizumab and the
      poly (ADP-ribose) polymerase (PARP) inhibitor olaparib have recently been shown
      to improve progression-free survival of patients with ovarian cancer with better
      hazard ratios in certain groups than have been seen previously. 

PMID- 24451761
TI  - Intraperitoneal treatment in ovarian cancer: the gynecologic oncology group
      perspective in 2012.
AB  - The peritoneal cavity is the major site of disease in ovarian cancer. The
      peritoneal predominance of disease provides a rationale for administration of
      chemotherapy within the peritoneal cavity. Intraperitoneal (IP) chemotherapy for
      ovarian cancer has been studied rigorously for more than 30 years and has been
      reproducibly shown to improve the survival of patients with ovarian cancer. Three
      large randomized trials of IP compared with intravenous (IV) therapy have
      demonstrated statistically significant improvement in clinical outcome measures.
      Despite this, the IP approach has not gained widespread acceptance in the
      treatment of ovarian cancer. Here, we review reported, recently completed, and
      ongoing trials of IP therapy in ovarian cancer including attempts to improve the
      tolerability and acceptance of this proven approach. 

PMID- 24451762
TI  - Dose-dense chemotherapy and neoadjuvant chemotherapy for ovarian cancer.
AB  - Two of the innovative chemotherapeutic approaches to ovarian cancer treatment,
      dose-dense chemotherapy and neoadjuvant chemotherapy, will be discussed herein.
      The primary concept of dose-dense chemotherapy is to administer the same
      cumulative dose of chemotherapy over a shorter period. Increased dose density is
      achieved by reducing the interval between each dose of chemotherapy. The Japanese
      Gynecologic Oncology Group (JGOG) first demonstrated the survival advantage of
      dose-dense weekly administration of paclitaxel in 2009. However, there are
      unanswered questions, such as the question of dose-dense carboplatin versus less
      dose-intensive regimens. Clear cell or mucinous carcinomas seem to need other
      strategies, such as targeted agents. The aim of neoadjuvant chemotherapy is to
      reduce tumor volume or spread before main treatment. This could then make the
      main procedures easier or less invasive, just like breast-conserving surgery
      after neoadjuvant chemotherapy. In advanced ovarian cancer, standard procedure is
      maximum primary debulking surgery followed by chemotherapy. Recently, a
      prospective randomized trial demonstrated that neoadjuvant chemotherapy followed
      by interval debulking surgery was not inferior to the standard procedure.
      However, there are several questions that remain unanswered, such as the suitable
      number of chemotherapy cycles before interval debulking surgery. Some of those
      questions regarding dose-dense chemotherapy or neoadjuvant chemotherapy may be
      resolved by ongoing or future prospective trials. 

PMID- 24451763
TI  - Uterine sarcomas: histology and its implications on therapy.
AB  - Uterine sarcomas are rare cancers, they comprise only 5% of all uterine
      malignancies. There are about 2,000 cases of uterine sarcoma diagnosed annually
      in the United States. Uterine sarcomas may be categorized as either favorable
      risk, low-grade malignancies with a relatively good prognosis or as poor-risk,
      high-grade cancers that carry a high risk for tumor recurrence and disease
      progression. Expert histologic review is critical for appropriate diagnosis and
      management. Uterine sarcoma histologies considered to carry a more favorable
      prognosis include low-grade endometrial stromal sarcomas and adenosarcomas. The
      high-grade sarcomas include high-grade leiomyosarcomas, high-grade
      undifferentiated endometrial sarcomas, and adenosarcomas with sarcomatous
      overgrowth. The favorable histology, low-grade uterine sarcomas may be cured with
      surgical resection of uterus-limited disease. These tumors are often hormone
      sensitive, and treatment with hormonal therapies may be efficacious for patients
      with advanced, unresectable disease. High-grade uterine leiomyosarcomas and
      undifferentiated endometrial sarcomas carry a high risk for recurrence, even
      after complete resection of uterus-limited disease. No adjuvant intervention has
      been shown to improve survival outcomes. Advanced, metastatic disease is
      generally treated with systemic cytotoxic therapies, which may result in
      objective response but is not curative. Selected patients with isolated
      metastatic disease and a long disease-free interval may benefit from
      metastatectomy. 

PMID- 24451764
TI  - Surgical options for recurrent uterine sarcomas.
AB  - Leiomyosarcoma, the most frequent pure uterine sarcoma, is an aggressive tumor
      with a tendency toward early relapse. Survival for patients with recurrent
      disease is poor. In contrast, endometrial stromal sarcoma, the second most common
      uterine sarcoma, is a more indolent malignancy with a tendency toward recurrence
      after a long latency period. The relative infrequency of both diseases makes the
      study and standardization of treatment for recurrent disease challenging.
      Treatment of recurrence with cytotoxic chemotherapy, radiation therapy, or
      hormone therapy produces modest to poor response rates. Surgical resection is one
      treatment modality offering the potential for cure and perhaps a more durable
      response than is seen with medical management. Although initial studies focused
      on pulmonary metastasectomy in recurrent soft tissue sarcoma, an increasingly
      large body of data specifically evaluating outcomes after both thoracic and
      extrathoracic metastasectomy in patients with recurrent uterine sarcoma is now
      available. Though no prospective trials have been conducted, retrospective
      comparisons of chemotherapy or radiation therapy with surgery for recurrent
      uterine sarcoma suggest improvement in disease-specific survival for the surgery
      group. Clearly defined factors are associated with better prognosis after
      surgical resection of recurrence, including a prolonged disease-free interval and
      complete resection of disease. In properly selected women, surgery and even
      repeated metastasectomy for recurrent disease may improve survival and should be
      considered. 

PMID- 24451765
TI  - Management of human papillomavirus-induced oropharynx cancer.
AB  - Oropharynx cancer (OPC) constitutes the most common location for squamous-cell
      head and neck cancer, and most OPC is caused by the human papilloma virus (HPV).
      Early-stage (American Joint Committee on Cancer [AJCC] stage I and II) disease
      should be treated with single modality surgery or radiotherapy whenever possible.
      More advanced presentations generally require combined-modality therapy with
      various combinations of surgery, radiotherapy, and chemotherapy or molecularly
      targeted therapy. All of these approaches expose patients to a substantial risk
      of serious long-term functional morbidity. HPV-induced OPC has a very favorable
      prognosis compared with its HPV-negative counterpart irrespective of the
      treatment platform that is used. Current clinical trials are investigating the
      concept of therapeutic deintensification with the dual objectives of decreasing
      toxicity and maintaining efficacy. 

PMID- 24451766
TI  - Important early advances in squamous cell carcinoma of the head and neck.
AB  - Therapeutic advances in squamous cell carcinomas of the head and neck (SCCHN) are
      attained by improvement in locoregional and/or distant disease control, as well
      as by reduction in treatment-related morbidity-especially long-term complications
      affecting normal organ functions and quality of life. New technological
      innovations in surgical management, such as transoral robotic surgery (TORS), and
      in radiotherapy (RT), such as proton and carbon ion therapy, bring promises of
      equal or superior efficacy outcomes coupled with the potential to minimize normal
      tissue toxicity. Scientific insights in the systemic treatment of SCCHN, such as
      novel approaches to overcome epidermal growth factor receptor (EGFR) resistance,
      may enable more effective molecular targeting in SCCHN beyond the current
      armamentarium of available agents. An overarching theme of these early
      multidisciplinary advances is to enable the delivery of precision-based
      therapeutic regimens from both the technical and scientific perspectives.
      Rigorous clinical trial evaluations are necessary to help define their roles in
      practice. 

PMID- 24451767
TI  - Application of genomic and proteomic technologies in biomarker discovery.
AB  - Sequencing of the human genome was completed in 2001. Building on the technology
      and experience of whole-exome sequencing, numerous cancer genomes have been
      sequenced, including head and neck squamous cell carcinoma (HNSCC) in 2011.
      Although DNA sequencing data reveals a complex genome with numerous mutations,
      the biologic interaction and clinical significance of the overall genetic
      aberrations are largely unknown. Comprehensive analyses of the tumors using
      genomics and proteomics beyond sequencing data can potentially accelerate the
      rate and number of biomarker discoveries to improve biology-driven classification
      of tumors for prognosis and patient selection for a specific therapy. In this
      review, we will summarize the current genomic and proteomic technologies, general
      biomarker-discovery paradigms using the technology and published data in HNSCC
      including potential clinical applications and limitations. 

PMID- 24451768
TI  - Evaluation of patients with disseminated or locoregionally advanced thyroid
      cancer: a primer for medical oncologists.
AB  - Historically, patients with thyroid cancers are managed by endocrinologists,
      surgeons and radiation oncologists. Due to recent progress in this field with
      advances in treatment of thyroid cancer, medical oncologists are now commonly
      involved in care of patients with advanced thyroid cancers. In this manuscript,
      we describe general principles in management of patients with various types of
      thyroid cancers including differentiated, medullary and anaplastic thyroid
      cancers. 

PMID- 24451769
TI  - Systemic therapeutic approaches to advanced thyroid cancers.
AB  - Until only recently, few effective systemic therapies were available to treat
      patients with metastatic thyroid cancers. Recent advances in better understanding
      the pathogenesis and altered signaling pathways-especially in medullary and
      differentiated thyroid cancers (MTCs and DTCs)-have begun to change this
      situation substantially. Vandetanib, an orally bioavailable inhibitor of the RET
      kinase that is constitutively activated in MTC, has now been approved by the U.S.
      Food and Drug Administration (FDA) for use in progressive and symptomatic
      metastatic MTC; it has been shown to delay time to progression relative to
      placebo in a randomized phase III trial. Further, vascular endothelial growth
      factor receptor (VEGF-R) inhibitory agents including sorafenib, sunitinib,
      pazopanib, and axitinib that are already approved in the United States for use in
      advanced renal cell carcinoma have shown high response rates in treating advanced
      DTCs in multiple phase II trials, and have become commonly used in progressive
      radioiodine-refractory metastatic DTC. Yet additional agents are now in
      development, with several including XL184 (cabozantinib) also showing promise in
      DTC and MTC. In anaplastic thyroid cancer (ATC), progress has been slower, with
      the greatest apparent gains resulting more from the application of systemic
      therapies earlier in the disease course, especially when used in conjunction with
      initial surgical and radiation therapies. Despite recent progress, additional
      effective systemic therapeutic approaches remain sorely needed for treating
      metastatic MTC, DTC, and ATC. 

PMID- 24451770
TI  - Predicting clinical outcome in B-chronic lymphocytic leukemia.
AB  - B-Chronic lymphocytic leukemia (CLL) is a relatively common B-cell malignancy
      that has a very heterogeneous clinical course, despite carrying the designation
      of "chronic," which is a gross oversimplification. Being able to give some
      estimate of the rates of disease progression and overall survival (OS) at first
      diagnosis is, therefore, important in CLL. The ability to accurately predict
      response to therapy, as well as subsequent duration of response to therapy, is
      required given the variability of current therapies to induce and sustain
      treatment responses. The holy grail of prognostics would be to state with
      accuracy which therapy or types of therapy are best for a given patient. Although
      there is no complete answer to prognostic counseling, there is a continued
      development of markers specific to the CLL B cell and/or to its environment, as
      well as of testing of prognostic models. These models use both traditional and
      novel prognostic markers that can aid in the dissection of outcome for early
      stage CLL in terms of progression risk and time to therapy. This has resulted in
      significant enhancement of our ability to guide and predict outcome for our
      patients with CLL. 

PMID- 24451771
TI  - Transplant in chronic lymphocytic leukemia: to do it or not and if so, when and
      how?
AB  - Most patients with chronic lymphocytic leukemia (CLL) have an indolent clinical
      course, but the disease remains incurable with standard therapy and the prognosis
      is dismal for those patients with disease refractory to available treatment
      options. The only potentially curative treatment is allogeneic hematopoietic stem
      cell transplantation (SCT), but since CLL is a disease of elderly patients, few
      patients are candidates for myeloablative allogeneic SCT. Although autologous SCT
      is feasible and has low treatment-related mortality, it is not curative. The
      widespread adoption of reduced-intensity conditioning (RIC) allogeneic SCT has
      made this approach applicable to the elderly patient population with CLL. This
      approach relies on the documented graft-versus-leukemia (GVL) effect and is
      strong in CLL. Steps to further decrease the morbidity and mortality of the RIC
      SCT and in particular to reduce the incidence of chronic extensive graft-versus
      host disease (GVHD) remain a major focus. Many potential treatments are available
      for CLL, and appropriate patient selection and SCT timing remain controversial
      and the focus of ongoing clinical trials. The use of SCT must always be weighed
      against the risk of the underlying disease, particularly in a setting where
      improvements in treatment are leading to improved outcome. The major challenge
      remains how to identify which patients with CLL merit this approach and where in
      the treatment course this treatment can be applied optimally. 

PMID- 24451772
TI  - Therapeutic advances in myeloproliferative neoplasms: the role of new-small
      molecule inhibitors.
AB  - The discovery that a somatic point mutation (JAK2V617F) in the Janus kinase 2
      (JAK2) is highly prevalent in patients with myeloproliferative neoplasms (MPNs)
      has been a crucial breakthrough in our understanding of the underlying molecular
      mechanisms of these diseases. Therefore, preclinical and clinical research in
      recent years has focused intensely on the development of new therapies targeted
      to JAK2. These efforts culminated in recent approval of ruxolitinib as the first
      official therapy for patients with intermediate- or high-risk myelofibrosis (MF).
      Therapy with JAK2 inhibitors substantially improves quality of life and reduces
      organomegaly in MF with or without JAKV617F mutation. Recent results suggest that
      patients with advanced MF may live longer when receiving therapy with
      ruxolitinib. However, JAK2 inhibitors do not eliminate the disease and new
      medications are needed to expand on the benefits seen with JAK2 inhibitors.
      Although many agents are still in the early stages of development, the wealth of
      publications and presentations has continued to support our growing understanding
      of the pathophysiology of MF as well as the potential short- and long-term
      outcomes of these new and diverse approaches to treatment. Focus of ongoing
      efforts is particularly on the improvements in anemia and fibrosis, as well as on
      rational combination trials of JAK2 inhibitors and other potentially active
      agents. Therapeutic potential and limitations of JAK2 inhibitors and other novel
      medications in clinical studies are reviewed. 

PMID- 24451773
TI  - Insights into the molecular genetics of myeloproliferative neoplasms.
AB  - The molecular biology of the BCR-ABL1-negative chronic myeloproliferative
      neoplasms (MPNs) has witnessed unprecedented advances since the discovery of the
      acquired JAK2 V617F mutation in 2005. Despite the high prevalence of JAK2 V617F
      in polycythemia vera (PV), essential thrombocythemia (ET), and primary
      myelofibrosis (PMF), and the common finding of dysregulated JAK-STAT signaling in
      these disorders, it is now appreciated that MPN pathogenesis can reflect the
      acquisition of multiple genetic mutations that alter several biologic pathways,
      including epigenetic control of gene expression. Although certain gene mutations
      are identified at higher frequencies with disease evolution to the blast phase,
      MPN initiation and progression are not explained by a single, temporal pattern of
      clonal changes. A complex interplay between acquired molecular abnormalities and
      host genetic background, in addition to the type and allelic burden of mutations,
      contributes to the phenotypic heterogeneity of MPNs. At the population level, an
      inherited predisposition to developing MPNs is linked to a relatively common JAK2
      associated haplotype (referred to as '46/1'), but it exhibits a relatively low
      penetrance. This review details the current state of knowledge of the molecular
      genetics of the classic MPNs PV, ET, and PMF and discusses the clinical
      implications of these findings. 

PMID- 24451774
TI  - Classification of myeloproliferative neoplasms and prognostic factors.
AB  - Myeloproliferative neoplasms (MPNs) are currently diagnosed according to the
      World Health Organization (WHO) criteria. Molecular profiling should include the
      analysis of JAK2 V617F (first, exon 12 only in V617F-negative polycythemia vera
      [PV]) and MPL mutations (in V617F-negative essential thrombocythemia [ET] and
      myelofibrosis [MF]). For patients with PV and ET, the risk stratification of low-
      and high-risk disease requires only two parameters: older than age 60 and prior
      history of thrombosis. Additionally, it might be important to monitor leukocyte
      count and know the mutational profile. Survival of patients with MF is defined by
      the International Prognostic Scoring System (IPSS) model at diagnosis and the
      Dynamic IPSS (DIPSS) anytime during the course of the disease. The IPSS and the
      DIPSS are based on patient age older than age 65, presence of constitutional
      symptoms, hemoglobin level less than 10 g/dL, leukocyte count greater than 25 *
      10(9)/L, and circulating blast cells 1% or greater. The DIPSS-plus adds critical
      prognostic information and suggests also considering cytogenetic categories,
      platelet count, and red blood cell transfusion need. 

PMID- 24451775
TI  - Lung cancer in Brazil.
AB  - Cancer is now the second leading cause of death in Brazil (after cardiovascular
      diseases) and a public health problem, with around 500,000 new cases in 2012.
      Excluding nonmelanoma skin cancer, lung cancer is the second most incident cancer
      type in men, with 17,210 expected new cases. In women, it is the fifth most
      incident cancer, with 10,110 expected new cases. The estimated age-adjusted lung
      cancer mortality rate is about 13/100,000 for men and 5.4/100,000 for women. Lung
      cancer rates in men increased until the early 1990s and decreased thereafter,
      especially in the younger population. In contrast, a steady upward trend was
      observed for women. The positive effects in men were probably due to the
      successful anti-tobacco campaign conducted in Brazil over the last decades, which
      led to a decrease in the adult smoking population, from 32% in the early 1980s to
      17% in the 2000s. Although the Brazilian National Cancer Institute is strongly
      committed to providing excellence in multimodality care to cancer patients,
      limitations in availability and adequate geographic distribution of specialists
      and well-equipped cancer centers are evident. Major disparities in patient access
      to proper staging and state-of-the-art treatment still exist. Considering that
      World Health Organization (WHO) officials estimate that cancer will become the
      number one cause of death in most developing countries, including Brazil, in the
      next decades, it is highly recommended for government authorities to implement
      firm actions to face this tremendous challenge. 

PMID- 24451776
TI  - Research and standard care: lung cancer in china.
AB  - China has an enormous burden from rising tobacco consumption and lung cancer
      incidence. Governmental intervention on lung cancer prevention is insufficient,
      and both incidence and mortality related to lung cancer are still on the rise.
      Treatment guidelines are available, but heterogeneity in the quality of care
      between centers, especially the disparity between urban and rural areas, have
      resulted in inconsistent care to patients with lung cancer. Despite knowledge on
      molecular-targeted therapy, only a small fraction of patients have access to
      routine EGFR mutation analysis. Platinum-based doublet chemotherapy remains the
      most commonly used regimen irrespective of mutation status. On a positive note,
      both clinical and translational research on lung cancer are in rapid progress.
      The Chinese Thoracic Oncology Group (CTONG) has already contributed substantially
      to the care of patients with lung cancer and is expected to continue in the
      trend. 

PMID- 24451777
TI  - Research and standard of care: lung cancer in romania.
AB  - In Romania, lung cancer is the most frequent cancer in men and fourth most
      frequent in women, and its incidence and mortality continue to rise. Recently,
      firm antitobacco policies were implemented, in agreement with the MPOWER
      strategies recommended by the World Health Organization (WHO). As of January
      2012, the recognized "official" standard of care in lung cancer is still
      represented by the 2009 edition of the European Society for Medical Oncology
      (ESMO) guidelines. Cancer treatment is free, as the National Program of Oncology
      covers the budget for all cytotoxic agents and targeted therapy. However,
      reimbursement for several expensive drugs such as pemetrexed, erlotinib, and
      bevacizumab is individually approved by a centralized commission. All new drugs
      registered in Europe by the European Medicines Agency are concomitantly
      registered in Romania. However, no new drugs (such as gefitinib) or new
      indications (such as first-line tyrosine-kinase inhibitors or maintenance
      treatment) have been accepted for reimbursement since 2008. Clinical research is
      rapidly growing, and Romanian centers demonstrate a high recruitment rate in
      pivotal trials, despite initial delays because of a slow approval of the studies
      by authorities. 

PMID- 24451778
TI  - A new model: physician-patient collaboration in online communities and the
      clinical practice of oncology.
AB  - The practice of medicine is in the midst of a fundamental transformation based on
      the new availability of health information through the Internet and other sources
      accessible by the broad lay public, as well as on the easy sharing of experiences
      and content through social media. This is occurring at a time when the volume of
      new information required for optimal medical care is exceeding that which an
      individual physician can feasibly follow and master. The changes in cancer care
      are especially acute as we experience an ongoing reclassification of many disease
      entities to reflect divisions by molecular variables, often with new clinical
      options now optimized for very limited patient subsets. The increasing complexity
      of the field, combined with the high stakes of optimizing treatment decisions and
      the growing availability of a wide range of information in the public domain,
      make oncology an area in which patients and caregivers are most motivated to
      become active seekers of medical information and participants in their care
      decisions. The credibility of the available online information in such a
      situation has emerged as a critical issue, but physicians have historically been
      reluctant to create content or interact with the lay public in online patient
      communities. Here we will highlight several examples of collaborative engagement
      between health care professionals and motivated patients in an online environment
      that illustrate how a new bidirectional or even networked model that is a product
      of the Internet age can accelerate clinical research and improve delivery of
      cancer care. 

PMID- 24451779
TI  - Lung cancer screening: promise and pitfalls.
AB  - The results of the National Lung Screening Trial (NLST) have provided the medical
      community and American public with considerable optimism about the potential to
      reduce lung cancer mortality with imaging-based screening. Designed as a
      randomized trial, the NLST has provided the first evidence of screening benefit
      by showing a 20% reduction in lung cancer mortality and a 6.7% reduction in all
      cause mortality with low dose helical computed tomography (LDCT) screening
      relative to chest X-ray. The major harms of LDCT screening include the potential
      for radiation-induced carcinogenesis; high false-positivity rates in individuals
      without lung cancer, and overdiagnosis. Following the results of the NLST, the
      National Comprehensive Cancer Network (NCCN) published the first of multiple lung
      cancer screening guidelines under development by major medical organizations.
      These recommendations amalgamated screening cohorts, practices, interpretations,
      and diagnostic follow-up based on the NLST and other published studies to provide
      guidance for the implementation of LDCT screening. There are major areas of
      opportunity to optimize implementation. These include standardizing practices in
      the screening setting, optimizing risk profiles for screening and for managing
      diagnostic evaluation in individuals with indeterminate nodules, developing
      interdisciplinary screening programs in conjunction with smoking cessation, and
      approaching all stakeholders systematically to ensure the broadest education and
      dissemination of screening benefits relative to risks. The incorporation of
      validated biomarkers of risk and preclinical lung cancer can substantially
      enhance the effectiveness screening programs. 

PMID- 24451780
TI  - Molecular testing of non-small cell lung carcinoma biopsy and cytology specimens.
AB  - During the past decade, substantial progress has been made in the
      characterization of molecular abnormalities in non-small cell carcinoma (NSCLC)
      tumors that are being used as molecular targets and predictive biomarkers for
      selection of targeted therapy. These recent advances in NSCLC targeted therapy
      require the analysis of a panel of molecular abnormalities in tumor specimens,
      including gene mutations (e.g., EGFR, KRAS, BRAF, DDR2), gene amplifications
      (e.g., MET, FGFR1), and fusions (e.g., EML4-ALK) by applying different methods to
      tumor tissue (biopsy) and cell (cytology) samples. However, the biopsy and
      cytology samples available for molecular testing in advanced metastatic NSCLC
      tumors are likely to be small specimens, including core needle biopsies and/or
      fine needle aspiration, which may limit the molecular and genomic analysis with
      currently available methods and technologies. In this process, the role of the
      pathologist is becoming increasingly important to adequately integrate both
      routine histopathologic assessment and molecular testing into the clinical
      pathology for proper tumor diagnosis and subsequent selection of the most
      appropriate therapy. 

PMID- 24451781
TI  - Multidisciplinary management of thymic carcinoma.
AB  - Thymic carcinomas represent approximately 10% of thymic tumors. In our approach
      to patients with thymic carcinoma, we emphasize multimodality treatment with
      close communication between the pathologist, thoracic surgeon, medical
      oncologist, and radiation oncologist. Given the paucity of high-quality clinical
      research data, treatment decisions are guided by a small amount of prospective
      trial data, retrospective reports, and clinical experience. Surgical management
      of thymic carcinoma must account for the more aggressive biology, higher degree
      of local invasion of neighboring structures, greater propensity for nodal
      metastasis, and higher risk of distant metastatic disease. Although surgical
      resection remains the most important component in the management of localized
      thymic tumors, radiation therapy (RT) may be used as adjuvant therapy after
      surgical resection or as the definitive treatment modality in patients who are
      deemed unresectable because of medical comorbidities or technical reasons.
      Systemic therapy for thymic carcinoma is used in two clinical scenarios:
      preoperative treatment and palliative therapy. First-line, platinum-based
      chemotherapy regimens are associated with response rates between 22% and 75%.
      Recent data from targeted therapy trials do not reveal a clear role for targeted
      therapies for patients with thymic carcinoma. 

PMID- 24451782
TI  - The creation of the international thymic malignancies interest group as a model
      for rare diseases.
AB  - Similar to other orphan diseases, little progress has been made in the past
      decades in thymic malignancies. A determination to make a difference, despite the
      challenges facing a rare disease, led to the formation of the International
      Thymic Malignancies Interest Group (ITMIG) in 2010. This organization has brought
      together the majority of those focused on the management of thymic malignancies
      and has built a foundation for scientific collaboration, including consistent use
      of terms, an international database, and multidisciplinary engagement of
      clinicians and researchers from around the world. ITMIG has embarked on the
      development of novel approaches to research particularly suited to a rare
      condition. ITMIG has gained substantial recognition for the rapid progress that
      has been made and serves as a model for the advancement of knowledge in a rare
      disease. 

PMID- 24451783
TI  - Thymoma: from chemotherapy to targeted therapy.
AB  - Thymic malignancies are rare epithelial tumors that may be aggressive and
      difficult to treat. Thymomas are frequently eligible for upfront surgical
      resection. However, nearly 30% of patients present with locally advanced tumor at
      time of diagnosis, and chemotherapy is then used to reduce the tumor burden
      possibly allowing subsequent surgery and/or radiotherapy. Metastatic and
      recurrent thymic malignancies may be similarly treated with chemotherapy. More
      recently, the molecular characterization of thymoma led to the identification of
      potentially druggable targets, laying the foundation to implement personalized
      medicine for patients. 

PMID- 24451784
TI  - What is the best strategy for incorporating new agents into the current treatment
      of follicular lymphoma?
AB  - Although there is increasing knowledge about the pathobiology of follicular
      lymphoma (FL), the incorporation of new agents is challenged by the long clinical
      course and inherent heterogeneity of the disease. Furthermore, a longstanding
      concept in FL is that although most patients have an indolent initial phase of
      disease, this is typically followed by sequentially shorter remission durations
      and justifies the continued intense search for new rationally designed agents.
      Ideally, there would be personalized prognostic tools, preemptive target
      identification, and means to predict response in individual patients. Short of
      having these tools, one conceptual approach is to consider FL as a series of
      clinical disease states divided between treatment-naive (low tumor burden and
      high tumor burden), relapsed (typically still chemoimmunotherapy-sensitive), and
      multiply relapsed (usually chemoimmunotherapy-resistant) disease. By applying
      what is known about the biology of FL along with the available agents, new
      treatment options can be better defined and tested within these clinical
      contexts. During the last few years, novel chemotherapeutics, biologic agents,
      monoclonal antibodies, antibody drug conjugates, and maintenance strategies are
      all either replacing or adding onto existing strategies. These new agents and
      approaches challenge the notion of inevitably shorter response durations, and
      offer hope of improved clinical outcomes compared with traditional sequential
      cytotoxic therapy. 

PMID- 24451785
TI  - What is the best first-line treatment strategy for patients with indolent
      lymphomas?
AB  - Although advanced follicular lymphoma is considered incurable, patient outcomes
      have improved over the last decade with the use of anti-CD20 monoclonal
      antibodies. Multiple treatment options are available and their use depends on
      clinical presentation (i.e., Ann Arbor stage, tumor burden, symptoms) and patient
      condition and age. Radiation therapy for patients with limited stage disease
      remains useful, although its use in the era of anti-CD20 antibodies should be re
      evaluated. Single-agent rituximab has been tested in multiple studies with
      patients with low tumor burden. Short treatment duration provides a response
      lasting 2 to 3 years, although the benefit of maintenance therapy with rituximab
      after induction therapy with rituximab remains unproven. When watchful waiting is
      not an option, a combination of rituximab with chemotherapy is the standard of
      care: alkylating agents with anthracycline or bendamustine appear to be the most
      widely used regimens, but alkylating agents alone may still be used in selected
      patients subgroups. The toxicity of regimens containing fludarabine appears to
      limit their indication as first-line treatment. In patients responding to one of
      these combinations, consolidation therapy with rituximab maintenance has been
      shown to prolong progression-free survival with acceptable toxicity. The benefit
      of radioimmunotherapy in first-line treatment is still uncertain. With patients
      surviving for many years, the therapeutic strategy of first-line management
      should weigh the quality and duration of response against the risk of long-term
      toxicities. 

PMID- 24451786
TI  - What is the role of transplantation for indolent lymphoma?
AB  - Despite advances in chemoimmunotherapy, indolent B-cell non-Hodgkin lymphomas (B
      NHLs) are generally not considered curable with this approach. Much attention has
      been paid to the prospect of hematopoietic cell transplantation (HCT) as a way to
      improve long-term outcomes for this group of diseases. Autologous (auto) HCT
      provides intensive conditioning therapy followed by rescue of hematopoiesis, and
      this has been shown in randomized studies to prolong survival compared with more
      standard chemotherapy, albeit with increased short-term toxicity and the
      potential for higher rates of secondary malignancies. Allogeneic (allo) HCT can
      provide anticancer effects beyond the conditioning therapy through the immune
      mediated graft-versus-lymphoma (GVL) effect. It can be administered following
      myeloablative (MA) conditioning or reduced-intensity (RI) regimens aimed at
      sufficiently suppressing the patient's immune system to allow engraftment of
      donor hematopoiesis. However, this same potentially curative alloreactivity of
      the engrafted immune system can lead to graft-versus-host disease (GVHD), a
      significant cause of morbidity and mortality following allo HCT. This article
      will discuss the current role of both auto HCT and allo HCT in the management of
      indolent lymphoma as well as the relative risks and benefits of each approach
      such that the reader can place this in context of the multitude of options
      available for patients with indolent B-NHL. 

PMID- 24451787
TI  - Stem cell transplantation for multiple myeloma: who, when, and what type?
AB  - Early randomized trials of high-dose chemotherapy with autologous stem cell
      rescue showed improved progression-free survival (PFS) over conventional
      chemotherapy. However, in the era of novel agents for myeloma in conjunction with
      the evolution of hematopoietic stem cell transplantation, many new questions
      arise. First, how can novel agents be incorporated into the transplant paradigm?
      Given the efficacy of new induction regimens, should transplant be delayed until
      relapse? Also, in the era of individualized medicine, chronologic age alone
      should not drive decisions regarding transplantation. Therefore, the feasibility
      and role of transplantation in older patients with myeloma is being studied. The
      controversy of transplant type (i.e., autologous compared with reduced intensity
      allogeneic transplant) remains unresolved. Several large international trials
      have demonstrated conflicting results in regard to an overall survival (OS)
      benefit with the allogeneic approach. The role of allogeneic transplant remains
      under study especially in the high-risk population, which has high relapse rates
      with traditional autologous approaches. Future directions to reduce relapse
      include post-transplantation consolidation and maintenance therapy with either
      approved agents or new agents and immunotherapy, either vaccine based or natural
      killer (NK) and T-cell based. 

PMID- 24451788
TI  - Upfront Therapy for Myeloma: Tailoring Therapy across the Disease Spectrum.
AB  - The treatment of multiple myeloma is evolving rapidly. Despite the number of
      regimens and combinations available, there is lack of data from phase III trials
      demonstrating superiority of one regimen over the other in terms of overall
      survival and/or quality of life. The only clear survival signals have come from
      studies that compared newer regimens with historic ones such as melphalan
      prednisone (MP) or vincristine-doxorubicin hydrochloride-thalidomide (VAD). Thus,
      the choice of therapy at present is often made based on physician discretion,
      bias, and limited data from phase II studies. Further, the regimens available
      have considerably different profiles in terms of safety, convenience, and cost.
      Given the dramatic variations in expected outcome depending on the various known
      prognostic factors, a risk-adapted strategy is required to provide the best
      available therapy to each patient based on host factors as well as prognostic
      markers of disease aggressiveness. This article reviews the current status of
      myeloma therapy and risk stratification. Results from major phase III trials are
      reviewed, and a risk-adapted individualized approach to therapy is presented and
      discussed. 

PMID- 24451789
TI  - Maintenance therapy for myeloma: how much, how long, and at what cost?
AB  - Maintenance therapy in multiple myeloma has been under investigation for more
      than 3 decades and has been without evidence of clear advantage in terms of
      progression-free survival (PFS) until the mid-2000s. Neither conventional
      chemotherapy, prednisone, nor interferon-based maintenance regimens offered any
      benefit after conventional or high-dose therapy. Thalidomide was the first drug,
      mainly given as maintenance after high dose therapy, to demonstrate clinical
      benefits in terms of PFS and, in some studies, of overall survival (OS). The role
      of other novel agents such as lenalidomide and bortezomib as maintenance therapy
      is emerging. Lenalidomide has been shown to reduce the risk of relapse with
      longer follow-up needed to see if this will translate into a survival benefit. At
      present, a number of key questions remain unanswered. What are the optimal dose
      and duration of those treatments? Is the risk of toxicity and second primary
      malignancies acceptable? Will the disease be more aggressive at time of relapse?
      Is the clinical benefit predicted by initial prognostic factors and response to
      previous therapy? Does maintenance therapy work by further eradication of minimal
      residual disease or by immunological control of the malignant clone? Ongoing
      randomized trials are evaluating lenalidomide and bortezomib, both in the
      transplant and nontransplant settings, to better define the role of these drugs
      as maintenance in multiple myeloma. 

PMID- 24451790
TI  - New options and new questions: how to select and sequence therapies for patients
      with metastatic melanoma.
AB  - Recent advances in the understanding of the melanoma biology and tumor immunology
      have yielded new treatment strategies for patients with advanced melanoma. Within
      the past year, the selective BRAF inhibitor vemurafenib and immune checkpoint
      inhibitor ipilimumab have been added to the treatment armamentarium. In addition,
      other molecularly targeted agents and immunotherapies are showing considerable
      promise. The availability of multiple, effective treatment options for patients
      with melanoma, although long sought, has complicated treatment decisions. This
      article will review the advances in our understanding of melanoma biology and
      tumor immunology, the current status of immunotherapy, the advances in
      molecularly targeted therapy for patients with BRAF mutant melanomas, the
      possible approaches to patients with BRAF wild-type (WT) tumors, and the current
      considerations for treatment selection of individual patients. 

PMID- 24451791
TI  - Antiemetic Use in Oncology: Updated Guideline Recommendations from ASCO.
AB  - In 2011, ASCO updated its guideline for the use of antiemetics in oncology,
      informed by a systematic review of the medical literature. This is an abbreviated
      version of that guideline, which is available in full at
      www.asco.org/guidelines/antiemetics. Key changes from the prior update in 2006
      include the following: Combined anthracycline and cyclophosphamide regimens were
      reclassified as highly emetic. Patients who receive this combination or any
      highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone,
      and an NK1 receptor antagonist. A large trial validated the equivalency of
      fosaprepitant, a single-day intravenous formulation, with aprepitant; either
      therapy is appropriate. Preferential use of palonosetron is recommended for
      moderate emetic risk regimens, combined with dexamethasone. For low-risk agents,
      patients can be offered dexamethasone before the first dose of chemotherapy.
      Patients undergoing high emetic risk radiation therapy should receive a 5-HT3
      receptor antagonist before each fraction and for 24 hours following treatment and
      may receive a 5-day course of dexamethasone during fractions 1 to 5. Continued
      symptom monitoring throughout therapy is recommended. Clinicians often
      underestimate the incidence of nausea, which is not as well controlled as
      vomiting. Detailed information about the development of the guideline as well as
      practice tools are available at www.asco.org/guidelines/antiemetics. 

PMID- 24451792
TI  - Chemotherapy-induced nausea and vomiting incidence and prevalence.
AB  - Although chemotherapy-induced nausea and vomiting is recognized as having been an
      important problem during the initial introduction of chemotherapy into the
      antineoplastic armamentarium, the assumption that this problem has already been
      solved can restrict optimal management and further advances. Underestimation of
      nausea and vomiting may have many causes. If these toxicities are assumed to be
      necessary properties of chemotherapy, then their incidence may be taken for
      granted. If nausea and vomiting appear after discharge from the clinic several
      days after chemotherapy, these toxicities may not be reported because of poor
      recall or because of efforts by patients to avoid unnecessary complaints.
      Physician education may be compromised if physicians see nausea and vomiting as
      population problems but not problems for their own patients. Failure to recognize
      nausea and vomiting as two distinct entities that may appear independently of
      each other can also limit understanding of the prevalence of these problems and
      efforts at effective management. Continued attention to the impact of nausea and
      vomiting on the patient experience will be necessary to insure optimal
      maintenance of quality of life. 

PMID- 24451793
TI  - New frontiers in mucositis.
AB  - Mucositis is among the most debilitating side effects of radiotherapy,
      chemotherapy, and targeted anticancer therapy. Research continues to escalate
      regarding key issues such as etiopathology, incidence and severity across
      different mucosae, relationships between mucosal and nonmucosal toxicities, and
      risk factors. This approach is being translated into enhanced management
      strategies. Recent technology advances provide an important foundation for this
      continuum. For example, evolution of applied genomics is fostering development of
      new algorithms to rapidly screen genomewide single-nucleotide polymorphisms
      (SNPs) for patient-associated risk prediction. This modeling will permit
      individual tailoring of the most effective, least toxic treatment in the future.
      The evolution of novel cancer therapeutics is changing the mucositis toxicity
      profile. These agents can be associated with unique mechanisms of mucosal damage.
      Additional research is needed to optimally manage toxicity caused by agents such
      as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase
      inhibitors, without reducing antitumor effect. There has similarly been
      heightened attention across the health professions regarding clinical practice
      guidelines for mucositis management in the years following the first published
      guidelines in 2004. New opportunities exist to more effectively interface this
      collective guideline portfolio by capitalizing upon novel technologies such as an
      Internet-based Wiki platform. Substantive progress thus continues across many
      domains associated with mucosal injury in oncology patients. In addition to
      enhancing oncology patient care, these advances are being integrated into high
      impact educational and scientific venues including the National Cancer Institute
      Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference
      on mucosal health and disease scheduled for June 2013. 

PMID- 24451794
TI  - Short- and Long-term Cardiovascular Complications of Cancer Treatment: Overview
      for the Practicing Oncologist.
AB  - As new therapies improve survival from cancer, attention to comorbid illness and
      complications of therapy-both short- and long-term-become much more important to
      improving not only quality of life but also overall survival. Recognized for its
      importance as the leading cause of death in the United States, heart disease
      often coexists with cancer, and cancer treatment may increase risk and/or
      severity. In addition, there are well-recognized cardiovascular toxicities of
      cancer treatment, including not only cardiomyopathy, but also hypertension,
      hypercholesterolemia, and others. Oncologists and cardiologists are working
      closely to learn more about the complex interaction and to improve management and
      outcome for patients. 

PMID- 24451795
TI  - Recent advances in cardiotoxicity of anticancer therapies.
AB  - The treatment of two major diseases in the Western world, cancer and heart
      disease, has improved significantly in recent years. Today, many more cancers are
      curable than in previous years. Cancer treatment often consists of chemotherapy,
      radiation therapy, and now also targeted therapy. All three types of treatment
      can lead to an increased risk of developing or of worsening a pre-existent
      cardiovascular disease either during the treatment, immediately afterward, or
      several years after cessation of therapy. Anthracyclines, a class of drugs that
      are also known as anthracycline antibiotics, and the drug cisplatin have
      contributed to the success of cancer treatment. However, these agents can cause
      cardiovascular disease during treatment, and studies have shown that the risk of
      disease persists for many years after treatment stops. Irradiation contributes
      significantly to this risk when the cardiovascular system is part of the
      radiation field. If the targeted therapy also inhibits the genes responsible for
      maintaining the function of the cardiovascular system, development of
      cardiovascular symptoms is inevitable. Therefore, it is essential to have a
      cardiovascular endpoint in trials with targeted therapy. When treatment stops,
      however, the effect on the cardiovascular system appears to cease, but it is not
      known whether the long-term risk of developing cardiovascular disease increases.
      Combined, these factors indicate that close cooperation between oncologists and
      cardiologists is essential to optimally benefit patients with cancer. 

PMID- 24451796
TI  - The oncologist as the patient with cancer or relative.
AB  - To an extent, physicians are familiar with the consequences of illness through
      their interactions with patients. However, when cancer becomes personal, the
      physician has an opportunity to gain greater insight into the intricacies of
      medical care, including its humanistic elements. Physicians who encounter cancer
      in themselves or in a relative may deepen their understanding of the patient
      experience. Their views provide a unique perspective, on the basis of the
      convergence of their medical knowledge and personal reaction to illness. They
      also confront distinct challenges specific to their work environment. An enhanced
      recognition of their viewpoints provides valuable information in the quest to
      alleviate patient suffering and explore the fundamentals of patient care. 

PMID- 24451797
TI  - Prolonged febrile neutropenia in the pediatric patient with cancer.
AB  - Infectious diseases continue to be major causes of morbidity and mortality in
      pediatric patients with cancer. Yet not all pediatric patients with cancer with
      fever and neutropenia are at equal risk for substantial morbidity or mortality
      from infection. Patients at highest risk for developing infectious complications
      are those with severe and prolonged neutropenia, substantial medical comorbidity,
      and hematologic malignancy, or recipients of stem-cell transplantation. These
      "high-risk" patients also have concomitant host immune deficits as well: severe
      mucositis, lymphopenia, hypogammaglobulinemia, and gut microbial dysbiosis.
      Because bacterial and fungal infections are the most common infectious
      complications, continuation of empirical antibacterial antibiotics that were
      initiated at the onset of febrile neutropenia and prompt initiation of empirical
      antifungal therapy in the setting of prolonged fever and neutropenia continue to
      be the standard of care. In high-risk patients, antibiotic therapy should be
      maintained until neutrophil counts have recovered. Adjunctive therapies have been
      shown to be ineffective (e.g., colony-stimulating factors) or necessitate further
      study (e.g., granulocyte infusions or keratinocyte growth factor treatment to
      heal mucositis). Prophylactic use of antibacterial and antifungal antibiotics in
      high-risk patients has shown promise but the fear of inducing antimicrobial
      resistant strains remains a deterrent. Finally, the novel concepts of
      manipulating the host gut microbiota and/or augmenting GI mucosal immunity to
      prevent invasive bacterial and fungal infections in pediatric patients with
      cancer offers great promise, but more definitive studies need to be performed. 

PMID- 24451798
TI  - Initial Management of Low-Risk Pediatric Fever and Neutropenia: Efficacy and
      Safety, Costs, Quality-of-Life Considerations, and Preferences.
AB  - Initial management options for pediatric low-risk fever and neutropenia (FN)
      include outpatient compared with inpatient management and oral compared with
      intravenous therapy. Single-arm and randomized trials have been conducted in
      children. Meta-analyses provide support for the equivalence of outpatient and
      inpatient approaches. Outpatient oral management may be associated with a higher
      risk of readmission compared with outpatient intravenous management in children
      with FN, although other outcomes such as treatment failure and discontinuation of
      the regimen because of adverse effects were similar. Importantly, there have been
      no reported deaths among low-risk children treated as outpatients or with oral
      antibiotics. Costs, whether derived directly or through cost-effectiveness
      analysis, are consistently reduced when an outpatient approach is used. Quality
      of life (QoL) and preferences should be considered in order to evaluate different
      strategies, plan programs, and anticipate uptake of outpatient programs. Using
      parent-proxy report, child QoL is consistently higher with outpatient approaches,
      although research evaluating child self-report is limited. Preferences
      incorporate estimated QoL, but, in addition, factor in issues such as costs,
      fear, anxiety, and logistical issues. Only approximately 50% of parents prefer
      outpatient management. Future research should develop tools to facilitate
      outpatient care and to measure caregiver burden associated with this strategy.
      Additional work should also focus on eliciting child preferences for outpatient
      management. Finally, studies of effectiveness of an ambulatory approach in the
      real-world setting outside of clinical trials are important. 

PMID- 24451799
TI  - Identification, management, and evaluation of children with cancer-predisposition
      syndromes.
AB  - A substantial proportion of childhood cancers are attributable to an underlying
      genetic syndrome or inherited susceptibility. Recognition of affected children
      allows for appropriate cancer risk assessment, genetic counseling, and testing.
      Identification of individuals who are at increased risk to develop cancers during
      childhood can guide cancer surveillance and clinical management, which may
      improve outcomes for both the patient and other at-risk relatives. The
      information provided through this article will focus on the current complexities
      involved in the evaluation and management of children with cancer-predisposing
      genetic conditions and highlight remaining questions for discussion. 

PMID- 24451800
TI  - Treating rare cancer in children: the importance of evidence.
AB  - The study of pediatric rare cancers, which account for approximately 9% of all
      childhood malignancies, has been hindered by their histologic heterogeneity and
      by their preferential occurrence in adolescents, a population that has been
      underrepresented in clinical trials sponsored by the National Cancer Institute.
      The use of cooperative group and investigator-initiated registries can help
      improve our ability to identify and select populations of patients with rare
      cancers that can benefit from single-arm studies, and incorporation of biologic
      aims and tissue banking can accelerate our understanding of the biology of these
      cancers. These studies should be promoted further through expansion of
      international outreach efforts. Well-designed preclinical models that accurately
      recapitulate human disease offer an attractive alternative to the study of rare
      cancers and may accelerate the process of target identification and drug
      discovery and development. The concept of specialized clinics for selected rare
      cancers has proven to be very successful in pediatric gastrointestinal tumors.
      This paradigm should be further explored in other rare cancers because it offers
      an unprecedented opportunity to collaborate closely with interested
      investigators. In addition, it offers patients an opportunity to discuss their
      disease with specialists, allows these patients to provide tissue for further
      research, and ultimately can promote the development of clinical trials that are
      unique for that specific disease. 

PMID- 24451801
TI  - Genetic alterations in childhood melanoma.
AB  - Melanoma is rare in children. However, the clinical features of the disease in
      this population have been well-documented through single-institution experiences
      and population-based analyses. Still, our understanding of the etiologic factors
      in children remains unclear and diagnosis of melanoma remains challenging in
      certain cases. This article reviews emerging evidence indicating that molecular
      characterization of these lesions in children may be of diagnostic and
      therapeutic value. 

PMID- 24451802
TI  - Desmoid-type fibromatosis in children: a step forward in the cooperative group
      setting.
AB  - Desmoid-type (aggressive) fibromatosis (desmoid tumor) is a soft tissue neoplasm
      that can occur in both children and adults. Although it is formally classified as
      an intermediate-grade neoplasm because of its propensity for locally invasive
      growth, it can lead to severe and life-threatening problems. Because metastases
      do not arise from desmoid tumor, therapeutic interventions have historically
      focused on surgery or radiation to achieve local tumor control. These approaches
      may be ineffective or impractical for some children. In those cases, systemic
      therapy with cytotoxic or noncytotoxic therapy has been used. Because of the
      relative rarity of this neoplasm in children, knowledge on the use of
      chemotherapy is based largely on anecdotal reports or retrospective series.
      Limited conclusions can be drawn, though, from these types of reports. In the
      last 10 years, two prospective phase II clinical trials of chemotherapy for
      children with desmoid tumor have been conducted in cooperative clinical trials
      centered in North America. We review the results of those clinical trials and
      suggest future directions for systematically approaching this disease to better
      define the role of chemotherapy for children with desmoid tumor. 

PMID- 24451803
TI  - Targeting the Insulin-Like Growth Factor (IGF) System Is Not as Simple as Just
      Targeting the Type 1 IGF Receptor.
AB  - Increased signaling of the insulin-like growth factor (IGF) system via
      alterations in expression levels of its components has been demonstrated in
      various tumor types. Numerous experimental studies have supported the involvement
      of the IGF system signaling axis in tumor initiation and progression. These
      studies, combined with data that link alterations in the levels of circulating
      IGFs with cancer risk and prognosis, have focused on the IGF-1 receptor (IGF-1R)
      as a therapeutic target for patients with cancer. As a consequence, most
      therapeutic strategies have been designed to specifically inhibit IGF-1R but have
      for the most part ignored the insulin receptor (IR), based on concerns that
      targeting IR would lead to unacceptable toxicity both because of its role in
      physiologic metabolism and because we frequently try to oversimplify biologic
      complexity whenever we are urged to find practical, friendly solutions for
      clinical practice. Although this is an understandable and necessary starting
      point in the complex and long-lasting processes that leads to translational
      biology, the crude reality of the results obtained from phase I and II studies
      suggest a need for researchers to be humble and go back to the drawing board.
      Cancer research has substantially neglected the role of IR, and it remains
      unclear whether and to what extent avoiding the inhibition of IR has compromised
      the efficacy of anti-IGF-1R therapy. Clarifying its role might also help us take
      advantage of older drugs that could offer new perspectives in cancer care. 

PMID- 24451804
TI  - Hedgehog Pathway in Pediatric Cancers: They're Not Just for Brain Tumors Anymore.
AB  - The Hedgehog (HH) pathway regulates fundamental processes in embryonic
      development, including stem cell maintenance, cell differentiation, tissue
      polarity, and cell proliferation. In the vertebrate pathway, Sonic hedgehog (SHH)
      binds to Patched1 (PTCH1), which relieves its inhibition of Smoothened (SMO),
      allowing the GLI family of transcription factors to translocate to the nucleus
      and activate HH target genes such as GLI1, GLI2, PTCH1, CYCLIN D1, BCL-2, and
      MYCN. The HH pathway is also an active participant in tumorigenesis. In 1996,
      loss-of-function mutation in PTCH1 was discovered to be the cause of nevoid basal
      cell carcinoma syndrome (NBCCS, or Gorlin syndrome), an autosomal dominant
      disease associated with increased rates of basal cell carcinoma (BCC),
      medulloblastoma (MB), and rarely, rhabdomyosarcoma. It is now estimated that 100%
      of sporadic BCC and up to 20% to 30% of MB also harbor activating HH pathway
      mutations. Together, these discoveries firmly established the linkage between HH
      pathway activation and cancer development. Intense research has since been
      focused on further defining the role of the HH pathway in BCC and MB and
      potential therapeutic strategies to inhibit HH signaling. Early clinical trials
      of SMO inhibitors have shown promising results in the treatment of adult BCC and
      SHH-driven MB. More recently, a number of other pediatric cancers have been
      reported to show HH activity, making these tumors potential candidates for HH
      inhibitor therapy. To date however, no HH pathway mutations have been identified
      in other pediatric cancers. This review will describe the HH pathway signaling in
      development and cancer with a focus on recent evidence for HH pathway activation
      in central nervous system (CNS) and non-CNS pediatric cancers. 

PMID- 24451805
TI  - Development and refinement of augmented treatment regimens for pediatric high
      risk acute lymphoblastic leukemia.
AB  - The 5-year survival rate for children and adolescents with acute lymphoblastic
      leukemia (ALL) is now at least 90%. However, clinical features (age and initial
      white blood cell count [WBC]), early treatment response, and the presence/absence
      of specific sentinel genomic lesions can identify subsets of high-risk (HR) ALL
      patients with a much higher risk of treatment failure. Chemotherapy regimens used
      to treat HR ALL have been refined over the past 3 decades through randomized
      clinical trials conducted by the Children's Oncology Group (COG) in North America
      and the Berlin-Frankfurt-Muenster (BFM) group in Western Europe. Contemporary COG
      HR ALL treatment regimens were developed from the BFM-76 regimen, with subsequent
      changes that led to development and refinement of a so-called augmented BFM
      (ABFM) regimen used today. Although contemporary COG and BFM treatment regimens
      are not identical, there are many more similarities than differences. With
      improvements in survival, it has become clear that although the outcome of some
      patients with HR ALL can be improved by optimizing use of standard cytotoxic
      chemotherapy agents, this approach has had only limited success for other patient
      subsets. In contrast, introduction of the tyrosine kinase inhibitor imatinib has
      led to dramatic outcome improvements for children and adolescents with
      Philadelphia chromosome-positive ALL. Genomic studies are identifying new
      sentinel genomic lesions that can serve as potential therapeutic targets, which
      will likely lead to the testing of novel and/or targeted therapies in more
      children with HR ALL. Such studies will require increased collaboration between
      Western European and North American cooperative groups. 

PMID- 24451806
TI  - Refining the role of radiation therapy in pediatric hodgkin lymphoma.
AB  - The role of radiation therapy in the treatment of pediatric Hodgkin lymphoma has
      continued to be refined, motivated by the desire to avoid disruption to normal
      tissue development and function and secondary carcinogenesis. Such progress has
      occurred in tandem with modifications of the multiagent chemotherapy regimens
      that have been used in place of or in combination with low-dose involved-field
      radiation that are also associated with dose-related risks of cardiopulmonary and
      gonadal dysfunction and leukemogenesis. Consequently, treatment strategies for
      young patients, who have an excellent prognosis of long-term survival, utilizes a
      risk-adapted approach that provides optimal efficacy for disease control whereas
      limiting toxicity associated with both radiation and chemotherapy. Because of the
      differences in age-related developmental status and gender-related sensitivity to
      chemotherapy and radiation toxicity, no single treatment approach is ideal for
      all pediatric patients. This manuscript summarizes results from published
      clinical trials with the goal of defining optimal treatment strategies for
      children and adolescents with Hodgkin lymphoma in regards to the use of radiation
      therapy. 

PMID- 24451807
TI  - Role of Doxorubicin in rhabdomyosarcoma: is the answer knowable?
AB  - The role of doxorubicin in treatment of rhabdomyosarcoma (RMS) has been
      controversial for 30 years. Despite its known activity in RMS, because of its
      risk of cardiotoxicity, its use is not justified in low-risk patients who have an
      excellent chance of cure with vincristine, actinomycin with or without
      cyclophosphamide, and primary tumor treatment. For patients with intermediate and
      high risks, the risk/benefit ratio must be carefully considered. In addition, the
      peak incidence of RMS is in toddlers, with whom the risk of cardiotoxicity of
      anthracyclines is higher. A number of trials both in North America and Europe,
      which are reviewed in this article, have investigated the role of doxorubicin in
      RMS, with no conclusive outcomes. In addition, differences in risk-group
      assignment on two sides of the Atlantic further complicate comparisons and
      analyses. The current European EpSSG 2005 study for high-risk RMS (by the
      European definition) may come closest to giving an answer to the role of
      doxorubicin in RMS. 

PMID- 24451808
TI  - Identification of novel biologic targets in the treatment of newly diagnosed
      diffuse intrinsic pontine glioma.
AB  - Diffuse intrinsic pontine gliomas (DIPGs) carry an extremely poor prognosis.
      Standard practice has been to base the diagnosis on classic imaging and clinical
      characteristics and to treat with focal radiation therapy, usually accompanied
      with experimental therapy. As a result of the desire to avoid upfront biopsy,
      little has been learned regarding the molecular features of this disease.
      Findings from several autopsy series have included loss of p53 and PTEN, and
      amplification of PDGFR. Based on these and other findings, murine models have
      been generated and provide a new tool for preclinical testing. DIPG biopsy at
      diagnosis has increasingly become incorporated into national protocols at several
      centers, bringing the prospect of a better understanding of DIPG biology in the
      future. Initial analyses of pretreatment tumors cast valuable new light and
      establish the importance of p53 inactivation and the RTK-PI3K pathway in this
      disease. 

PMID- 24451809
TI  - Is biopsy safe in children with newly diagnosed diffuse intrinsic pontine glioma?
AB  - Diffuse intrinsic pontine gliomas (DIPGs), with a median survival of 9 months,
      represent the biggest therapeutic challenge in pediatric neuro-oncology. Despite
      many clinical trials, no major improvements in treatment have been made over the
      past 30 years. In most cases, biopsy is not needed for diagnosis because DIPG
      diagnosis is based on a typical clinical picture with radiologic evidence on
      magnetic resonance imaging. Therefore, little data on newly diagnosed DIPG have
      been published and are confounded by including autopsy (i.e., postradiation
      therapy) cases. In most cancers, advancing to cure has been linked to the
      discovery of relevant biomarkers, only found by access to tissue. Therefore, to
      further understand the biology of DIPG, fresh tissue samples must be obtained at
      diagnosis. However, most neurosurgical teams are reluctant to perform biopsy in
      pediatric patients, citing potential risks and lack of direct benefit. Yet, in
      reviewing 90 patients with and the published data on brainstem biopsy, these
      procedures have a diagnostic yield and morbidity and mortality rates similar to
      those reported for other brain locations. In addition, the quality and quantity
      of the material obtained confirm the diagnosis and inform an extended molecular
      screen, including biomarker study-information important to designing next
      generation trials with targeted agents. Stereotactic biopsies can be considered a
      safe procedure in well-trained neurosurgical teams and could be incorporated in
      well-defined protocols for patients with DIPG. 

PMID- 24451810
TI  - Ethics of biopsy in children with newly diagnosed diffuse intrinsic pontine
      glioma.
AB  - To understand the ethical dilemmas that beset this issue of biopsy in children
      with newly diagnosed diffuse intrinsic pontine glioma, one must understand both
      the history behind it and the current dominant interpretation of ethics through
      the medium of the institutional review boards. It is also important to understand
      that this article represents the author's personal viewpoint. At a consensus
      meeting to discuss the issue of biopsies in Diffuse Intrinsic Pontine Glioma
      (DIPG) at the National institutes of Health held in the fall of 2011, there were
      a variety of opinions expressed. 

PMID- 24451811
TI  - Communication and decision support for children with advanced cancer and their
      families.
AB  - Clinician communication related to treatment decision making is a fundamentally
      important health care intervention and is often reported by parents of seriously
      ill children to be the most valued of clinician skills. Since different children
      and families have different communication styles and expectations, and since
      these may change over the course of the illness experience, one of the early and
      recurring tasks is to clarify and work with these diverse styles and
      expectations. Adopting a stance of compassionate desire to know more about
      patients and families, in addition to imparting information, is vital, and can be
      facilitated by following a general strategy of "ask, tell, ask." In addition to
      the exchange of information, communication between clinician and patient and
      family also involves the signaling and exchange of emotions, in which the pace,
      verbal inflection, and body language of the conversation are fundamental.
      Discussions about prognosis and goals of care, while needing to be handled in a
      gentle manner, should start early in the illness experience and be revised
      whenever there is a relapse or major complication. Children often want to
      participate in these conversations to a degree of their own choosing, which they
      themselves can clarify. Effective and empathetic clinician communication can
      greatly facilitate decision making and care for children with advanced cancer and
      their families, and provide a substantial source of comfort. 

PMID- 24451812
TI  - How to decide whether to offer and use "nonstandard" therapies in patients with
      advanced sarcomas and gastrointestinal stromal tumors: global variations in
      clinical practice, assessment, and access to therapies in diseases with limited
      incidence and data.
AB  - As cancer is more generally recognized as a collection of various rare diseases
      rather than a homogeneous illness, sarcomas have become a model for the manner in
      which data can and cannot be used to drive clinical decision making. In this
      article, we explore the limitations of data generated in rare diseases such as
      sarcomas to provide an evidence base for clinical practice. How should patients
      be treated if there is no "standard" that offers "proof" of clinical benefit? By
      asking this question, we also raise the issue of what constitutes "clinical
      benefit"-and how to measure that-for patients with sarcomas and other rare
      diseases. As physicians become more accountable for decisions-and yet are always
      accountable to the patients and families who rely on them to provide the best and
      most appropriate care-oncologists must be cognizant of the limitations of data in
      rare diseases and be ready to justify actions that are in the best medical and
      social interests of patients. 

PMID- 24451813
TI  - Targeted therapy in sarcoma: should we be lumpers or splitters?
AB  - The identification of KIT as a critical driver in the pathogenesis of GI stromal
      tumor (GIST), and its subsequent inhibition with imatinib, have resulted in
      tremendous efforts to identify other potential therapeutic targets for the
      heterogeneous group of diseases known as sarcomas. Because of the rarity of
      sarcoma and the often limited number of patients per individual sarcoma subtype,
      clinical trials to date have often utilized unselected patient populations
      including multiple subtypes. Although this strategy increases the ease with which
      a particular trial may accrue patients, statistically significant therapeutic
      responses across an unselected patient population are often limited. Furthermore,
      in the absence of biologic correlatives, the identification of significant
      activity and subsequent interpretation of clinical trial results utilizing
      targeted therapies for this patient population have been challenging. However,
      hints have emerged, on the basis of preclinical and clinical observations, to
      suggest that certain targeted therapeutic approaches are appropriate in select
      histologic subtypes. This brief review will highlight data supporting the use of
      targeted therapy in both unselected and selected sarcoma patient populations. 

PMID- 24451814
TI  - Adjuvant treatment of gastrointestinal stromal tumor: the proof, the pro, and the
      practice.
AB  - Gastrointestinal stromal tumors (GIST) are rare tumors, but they are the most
      common mesenchymal tumor of the gastrointestinal tract, driven by mutations in
      KIT and PDGF. The KIT and PDGF inhibiting agent imatinib has been tested as
      adjuvant postsurgery in GIST patients with an intermediate or high risk of
      relapse. Two of three prospective, randomized controlled studies have meanwhile
      been reported. The American College of Surgical Oncology Group (ACOSOG) in 713
      patients reported a relapse-free survival benefit for adjuvant imatinib given for
      1 year, but not an overall survival benefit. The Scandinavian Sarcoma Group (SSG)
      performed a study comparing 1 year of imatinib to 3 years of imatinib. At 3 years
      the overall survival (OS) in patients with 3 years of imatinib therapy was
      similar to the OS in those with 1 year of imatinib 96% and 94% respectively,
      while at 5 years these numbers were 92% and 82% (HR: 0.45; 95% CI [0.22-0.89]; p
      = 0.019). Data from the largest study, conducted by the European Organisation for
      Research and Treatment of Cancer (EORTC) in 908 patients randomly assigned to
      receive either 2 years of adjuvant imatinib or no imatinib, have not yet been
      reported. Based on the current evidence, 3 years of imatinib at a daily dose of
      400 mg should be considered in patients with a 50% or higher risk of relapse
      within 5 years after surgery. The evidence and the remaining caveats are
      discussed. 

PMID- 24451815
TI  - Management of tyrosine kinase inhibitor-resistant gastrointestinal stromal
      tumors.
AB  - The treatment of gastrointestinal stromal tumors (GISTs) has been a model for
      targeted cancer therapy. The discovery of driver somatic mutations in the KIT and
      PDGFRA receptor tyrosine kinases led to a shift of therapy from conventional
      cytotoxic chemotherapy to inhibitors of these receptors. Targeted molecular
      therapy of GIST has markedly increased the overall survival of patients with
      advanced disease. However, the ability of kinase therapy to control metastatic
      disease is ultimately limited by the ability of these agents to overcome
      intrinsic or acquired resistance mechanisms. Ongoing basic and clinical research
      is focusing on identifying new agents to inhibit KIT/PDGFRA kinase activity
      and/or other novel molecular targets in GIST. 

PMID- 24451816
TI  - Opportunities and pitfalls of targeted therapeutic combinations in solid tumors.
AB  - Recent advances in cancer biology have led to the discovery and development of
      chemical compounds and drugs that target specific cellular receptors, mediators,
      or effectors that are central to oncogenic survival, growth, and invasion.
      However, the complexity of tumor biology makes it is unrealistic to expect an
      antitumor therapeutic to be successful based on the inhibition of a single target
      or even a lone signaling pathway. Therefore, the potential success of such
      "targeted therapies" is likely to require the development of multiagent
      combinations. Combination strategies have a greater likelihood of addressing
      issues with genetically complex tumors, potentially avoiding drug resistance
      mechanisms through the inhibition of escape signaling pathways and slowing the
      development of newly resistant tumor cells. Combination regimes also have the
      potential of enhancing target inhibition through synergistic antitumor effects
      and minimizing drug-related toxicities to patients. However, numerous challenges
      to developing these combinations exist. This review will focus on the
      opportunities and pitfalls of developing novel targeted drug combinations, with a
      particular focus on early-phase drug development, where the greatest challenges
      exist, analyzing key points for the design and development of clinical trials for
      combinations of targeted agents. 

PMID- 24451817
TI  - Combination Therapies Building on the Efficacy of CTLA4 and BRAF Inhibitors for
      Metastatic Melanoma.
AB  - The demonstration of improved survival with the anti-CTLA4 antibody ipilimumab
      and the BRAF inhibitor vemurafenib in patients with metastatic melanoma is
      arguably the most significant advance in the treatment for these patients in the
      last 30 years. However, the majority of patients will either not experience
      response, or will experience response and then progression, when receiving these
      therapies, so additional treatment options are required. Since these agents have
      been developed with a refined understanding of their mechanism of action and
      mechanisms leading to resistance are being elucidated, then combination therapies
      building on these single-agent therapies can be designed rationally. Such
      combinations are being tested both preclinically and in the clinic, and provide a
      strong promise to improve on the current treatment approaches for patients with
      metastatic melanoma. 

PMID- 24451818
TI  - Mechanisms of Resistance to Mitogen-Activated Protein Kinase Pathway Inhibition
      in BRAF-Mutant Melanoma.
AB  - Anticancer drug resistance remains a crucial impediment to the care of many
      patients with cancer. Although the exact mechanisms of resistance may differ for
      each therapy, common mechanisms of resistance predominate, including drug
      inactivation or modification, mutation of the target protein, reduced drug
      accumulation, or bypass of target inhibition. With the discovery and use of
      targeted therapies (such as small-molecule kinase inhibitors), resistance has
      received renewed attention-especially in light of the dramatic responses that may
      emerge from such therapeutics in particular genetic or molecular contexts.
      Recently, the mitogen-activated protein kinase (MAPK) pathway has become
      exemplary in this regard, since it is activated in many different cancers. Drugs
      targeting RAF and MAPK kinase (MEK) are currently in clinical trials for the
      treatment of several types of cancer. Vemurafenib, a selective RAF kinase
      inhibitor recently approved for the treatment of BRAF(V600E) melanoma, shows
      strong efficacy initially; however, the development of resistance is nearly
      ubiquitous. In vitro testing and analysis of patient samples have uncovered
      several mechanisms of resistance to RAF inhibition. Surprisingly, mutations in
      the drug-binding pocket have not thus far been observed; however, other
      alterations at the level of RAF, as well as downstream activation of MEK and
      bypass of MEK/extracellular signal-regulated kinase (ERK) signaling altogether,
      confer resistance to vemurafenib. Looking forward, combined RAF and MEK inhibitor
      treatments may improve efficacy-yet we must anticipate mechanisms of resistance
      to this combination as well. Therefore, understanding and/or determining the
      mechanism of resistance are paramount to effective cancer treatment. 

PMID- 24451819
TI  - Mechanisms of resistance to targeted therapies in acute myeloid leukemia and
      chronic myeloid leukemia.
AB  - Small molecule kinase inhibitors of BCR-ABL in chronic myeloid leukemia (CML) and
      of FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in acute
      myeloid leukemia (AML) have been successful at achieving remissions in these
      diseases as monotherapy, but these leukemias do not initially respond in a subset
      of patients (primary resistance) and they progress in an additional group of
      patients after an initial response (secondary resistance). Resistance to these
      agents can be divided into mechanisms that allow reactivation kinase activity and
      those that bypass reliance on oncogenic signaling mediated by the target kinase.
      Elucidation of clinical resistance mechanisms to targeted therapies for patients
      can provide important insights into disease pathogenesis and signaling. 

PMID- 24451820
TI  - Translating PI3K-Delta Inhibitors to the Clinic in Chronic Lymphocytic Leukemia:
      The Story of CAL-101 (GS1101).
AB  - Targeted therapy with imatinib has transformed the treatment of chronic myeloid
      leukemia (CML). Unlike CML, chronic lymphocytic leukemia (CLL) lacks a common
      genetic aberration but does demonstrate constitutive activation of PI3-kinase
      (PI3K) as compared to normal B cells. This constitutively active PI3K in CLL
      likely relates to tonic B-cell receptor signaling that is present across a wide
      variety of B-cell malignancies. Although PI3K is quite proximal and represents an
      ideal target to pharmacologically modulate, the complexity of this pathway on
      which many normal functions are dependent had for many years been problematic.
      The p110 delta isoform of PI3K is relatively specific to hematopoietic cells, and
      elegant mouse studies where p110 delta was genetically inactivated demonstrated
      only a selective B-cell defect. Subsequent development of a potent, selective
      p110 delta inhibitor prompted translation into the clinic for the treatment of
      CLL and low-grade non-Hodgkin lymphoma (NHL). From the first patient treated
      where a dramatic early nodal response was noted, considerable excitement has
      developed for this class of drugs in CLL and NHL. We will summarize the
      development process of CAL-101 (now GS1101) in the treatment of chronic lymphoid
      malignancies such as CLL. 

PMID- 24451821
TI  - Approval of New Agents after Phase II Trials.
AB  - Cancer drug approval has evolved as the understanding of cancer biology, and the
      ability to select patients for trials of targeted agents, has matured. The
      longstanding reliance on Phase III trials to prove drug efficacy and positive
      impact on patient survival may no longer be necessary, as early trials,
      particularly the expansion phase of a Phase I trial, may provide convincing
      evidence of a high response rate to a targeted drug in a patient population who
      has been poorly responsive to conventional therapy. If the new drug produces no
      safety signals of great concern, and if a validated biomarker for patient
      selection has been established and is readily available, accelerated approval may
      be achievable prior to completion of a randomized trial. The advantages, and
      potential downside, of rapid approval scenarios will be discussed in this
      article. 

PMID- 24451822
TI  - Are oncologists accountable only to patients or also to their families? An
      international perspective.
AB  - In most societies, health professionals traditionally carry responsibility only
      toward their patients. However, this is not the case in all cultures. In the
      contemporary practice of oncology in Western cultures, there is a shift toward
      assuming broader responsibility for patients with cancer' families during the
      illness course, the grieving stage, and in cancer prevention and genetic
      counseling. Traditional family, community, and religious values play a central
      role in determining people's perceptions and attitudes toward life and death as
      well as toward caregiving for a sick relative. The meaning of cancer illness
      within the family culture is thus influenced not only by each individual's values
      and beliefs but also by the family's makeup and dynamics, as well as their taboos
      and secrets. Global cancer care should therefore be directed at the family as a
      unit, while respecting patient autonomy and privacy. This reappraisal of our
      traditional understanding of physicians' duty as solely directed at the patient
      is reflected in the recent US trend toward a patient- and family-centered care
      approach. An additional challenge for oncology professionals is to integrate and
      tailor interventions toward the needs of both care recipients and caregivers and
      relate it to this dyad as the basic and enduring unit of care. 

PMID- 24451823
TI  - The Oncologist's Duty to Provide Hope: Fact or Fiction?
AB  - There are many sources of conflict in oncology. Conflicts arise because there are
      numerous therapeutic options, each of which is imperfect, and these conflicts
      produce ethical dilemmas. A recent American Medical Association (AMA) publication
      outlined the principles of medical ethics for managing conflicts. Common
      conflicts in oncology include whether to resuscitate, to give more chemotherapy,
      and how much truth to tell. These conflicts are magnified because of the life and
      death scenario of advanced cancer. Denial, avoidance, and hope are psychologic
      mechanisms that enable adaptation to the life-threatening circumstances. Hope is
      widely written about though poorly understood and defined. Ethical statements
      regarding its virtue and importance to preserve are frequently given. In an
      effort to progress the understanding of hope, two critical features are defined:
      (1) hope as a thought process only exists in the future, and (2) hope is only
      ever associated with positive and good thoughts. The future is unknown and
      uncertain; therefore, hoping can be manipulated by presenting statistics in a way
      to boost hoping. Thus a dilemma and specific ethical responsibility falls on
      oncologists when discussing conflicts. Furthermore, since hope is a subjective
      assessment of a possibility that is considered "good" by the hoper, it cannot be
      perceived as "false." "False hope" is an erroneous assessment. Finally, this
      article introduces the concept that there might be a role to stop hoping-since
      hope of the future is also filled with doubt and fear-and instead live in the
      present and try to find joy and meaning today. 

PMID- 24451824
TI  - Onclogists' difficulties in facing and disclosing medical errors: suggestions for
      the clinic.
AB  - Along with improved safety measures and changes in the culture of medicine,
      communication is key to reducing the effect of medical errors and to easing the
      medical, psychologic, and existential burdens they impose on all parties.
      Disclosure demonstrates respect for patients' autonomy and promotes patient's
      involvement in informed decision making about ways to correct or alleviate the
      effects of the error. It also enhances oncologists' integrity and helps restore
      trust in the patient-doctor relationship. Because of the complexity of cancer
      treatments and the uncertainty regarding outcomes in oncology, oncologists may
      rationalize nondisclosure as a way to avoid adding to the physical and
      existential suffering of their patients. Although there is broad agreement among
      professional and regulatory bodies, as well as medical ethicists, that physicians
      should disclose errors to patients-and physicians largely support disclosure of
      error to patients-studies show discrepancy between physicians' responses to
      hypothetical clinical scenarios of truth telling about medical errors and actual
      practices of withholding or tempering the truth. Among common reasons for
      avoiding disclosure are risk of malpractice lawsuits, fear of being exposed as
      incompetent, and feeling shame before patients and colleagues. Proper disclosure,
      however, including a sincere apology, should be part of the management of errors
      and of their long-term aftermaths. In disclosing medical errors, it is essential
      for oncologists to pay equal attention to the medical and the emotional aspects
      of the information they are giving and the reaction that it elicits in patients
      and families. Specific communication skills regarding disclosure of medical
      errors can be learned. 

PMID- 24451825
TI  - Preventing errors in oncology: perspective of a physician who is also a cancer
      patient.
AB  - This article presents my personal experiences as a physician who underwent
      laryngectomy for hypopharyngeal squamous cell carcinoma. I describe the numerous
      medical and surgical errors that occurred during my hospitalization at three
      different medical centers. It is my hope that my presentation will contribute to
      the reduction of such errors and lead to a safer hospital environment for
      patients. 

PMID- 24451826
TI  - Adjuvant Treatments for Localized Advanced Gastric Cancer: Differences among
      Geographic Regions.
AB  - After much debate, adjuvant therapy has become the standard of care worldwide for
      resected localized gastric cancer. However, geographic differences exist in
      standard adjuvant treatments: postoperative chemoradiation in North America,
      perioperative chemotherapy in the United Kingdom, and postoperative chemotherapy
      in East Asia. Now that D2 gastrectomy has been recognized as the optimal surgery
      for localized gastric cancer in the West as well as in Asia, the standard
      adjuvant treatments used in the West may need to be reconsidered. One of the most
      important issues in adjuvant therapy for localized gastric cancer is how to
      improve the clinical outcomes of current standard treatments. Recent Cancer and
      Leukemia Group B (CALGB) and AMC studies suggest that simply intensifying
      chemotherapy by adding more agents or prolonging treatment duration is
      insufficient. However, new strategies like early initiation of chemotherapy
      and/or intraperitoneal chemotherapy may further improve the current standard
      adjuvant therapy. In the era of targeted therapy, the role of biologic agents for
      gastric cancer should also be explored in the adjuvant setting. With a deeper
      understanding of the molecular biology of gastric cancer, adjuvant therapy for
      patients with localized gastric cancer can be optimized and individualized. 

PMID- 24451827
TI  - Overdiagnosis and overtreatment of prostate cancer.
AB  - Prostate cancer is a ubiquitous disease, affecting as many as two-thirds of men
      in their 60s. Through widespread prostate-specific antigen (PSA) testing,
      increasing rates of prostate biopsy, and increased sampling of the prostate, a
      larger fraction of low-grade, low-volume tumors have been detected, consistent
      with tumors often found at autopsy. These tumors have historically been treated
      in a manner similar to that used for higher-grade tumors but, more recently, it
      has become evident that with a plan of active surveillance that reserves
      treatment for only those patients whose tumors show evidence of progression, very
      high disease-specific survival can be achieved. Unfortunately, the frequency of
      recommendation of an active surveillance strategy in the United States is low. An
      alternative strategy to improve prostate cancer detection is through selected
      biopsy of those men who are at greater risk of harboring high-grade, potentially
      lethal cancer. This strategy is currently possible through the use of risk
      assessment tools such as the Prostate Cancer Prevention Trial Risk Calculator
      (www.prostate.cancer.risk.calculator.com) as well as others. These tools can
      predict with considerable accuracy a man's risk of low-grade and high-grade
      cancer, allowing informed decision making for the patient with a goal of
      detection of high-risk disease. Ultimately, other biomarkers including PCA3,
      TMPRSS2:ERG, and [-2]proPSA will likely aid in discriminating these two types of
      cancer before biopsy. 

PMID- 24451828
TI  - Core elements of the patient protection and affordable care act and their
      relevance to the delivery of high-quality cancer care.
AB  - The Affordable Care Act (ACA) contains many provisions that affect cancer care.
      The provisions of health care reform aim to improve access to quality cancer
      care, particularly among the most vulnerable Americans. However, health care
      reform also offers many challenges and opportunities that affect every
      stakeholder in oncology. This article summarizes the ACA provisions relevant to
      oncology, discusses the ethical implications for the oncology caregiver, and
      describes the effects on specific oncology stakeholders. 

PMID- 24451829
TI  - Overdiagnosis and overtreatment of breast cancer.
AB  - Breast cancer is the most common cancer in women. Through greater awareness,
      mammographic screening, and aggressive biopsy of calcifications, the proportion
      of low-grade, early stage cancers and in situ lesions among all breast cancers
      has risen substantially. The introduction of molecular testing has increased the
      recognition of lower risk subtypes, and less aggressive treatments are more
      commonly recommended for these subtypes. Mammographically detected breast cancers
      are much more likely to have low-risk biology than symptomatic tumors found
      between screenings (interval cancers) or that present as clinical masses.
      Recognizing the lower risk associated with these lesions and the ability to
      confirm the risk with molecular tests should safely enable the use of less
      aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or
      what have been called stage I cancers, in and of themselves are not life
      threatening. In situ lesions have been treated in a manner similar to that of
      invasive cancer, but there is little evidence to support that this practice has
      improved mortality. It is also being recognized that DCIS lesions are
      heterogeneous, and a substantial proportion of them may in fact be precursors of
      more indolent invasive cancers. Increasing evidence suggests that these lesions
      are being overtreated. The introduction of molecular tests should be able to help
      usher in a change in approach to these lesions. Reclassifying these lesions as
      part of the spectrum of high-risk lesions enables the use of a prevention
      approach. Learning from the experience with active surveillance in prostate
      cancer should empower the introduction of new approaches, with a focus on
      preventing invasive cancer, especially given that there are effective, United
      States Food and Drug Administration (FDA)-approved breast cancer preventive
      interventions. 

PMID- 24451830
TI  - Reducing the cost of cancer care: how to bend the curve downward.
AB  - Health care and cancer care costs are rising unsustainably such that insurance
      costs have doubled in 10 years. Oncologists find themselves both victims of high
      costs and the cause of high-cost care by what we do and what we do not do. We
      previously outlined five ways that oncologists could personally bend the cost
      curve downward and five societal attitudes that would require change to lower
      costs. Here, we present some practical ways to reduce costs while maintaining or
      improving quality, including: 1) evidence-based surveillance after curative
      therapy; 2) reduced use of white cell stimulating factors (filgrastim and
      pegfilgrastim); 3) better integration of palliative care into usual oncology
      care; and 4) use of evidence-based, cost-conscious clinical pathways that allow
      appropriate care and lead to equal or better outcomes at one-third lower cost. 

PMID- 24451831
TI  - Why Hasn't Genomic Testing Changed the Landscape in Clinical Oncology?
AB  - The "omics" revolution produced great optimism that tumor biomarker tests based
      on high-order analysis of multiple (sometimes thousands) of factors would result
      in truly personalized oncologic care. Unfortunately, 10 years into the
      revolution, the promise of omics-based research has not yet been realized. The
      factors behind the slow progress in omics-based clinical care are many. First,
      over the last 15 years, there has been a gradual recognition of the importance of
      conducting tumor biomarker science with the kind of rigor that has traditionally
      been used for therapeutic research. However, this recognition has only recently
      been applied widely, and therefore most tumor biomarkers have insufficiently high
      levels of evidence to determine clinical utility. Second, omics-based research
      offers its own particular set of concerns, especially in regard to overfitting
      computational models and false discovery rates. Researchers and clinicians need
      to understand the importance of analytic validity, and the difference between
      clinical/biologic validity and clinical utility. The latter is required to
      introduce a tumor biomarker test of any kind (single analyte or omics-based), and
      are ideally generated by carefully planned and properly conducted "prospective
      retrospective" or truly prospective clinical trials. Only carefully planned
      studies, which take all three of these into account and in which the
      investigators are aware and recognize the enormous risk of unintended bias and
      overfitting inherent in omics-based test development, will ultimately result in
      translation of the exciting new technologies into better care for patients with
      cancer. 

PMID- 24451832
TI  - Planning for the future: the role of nurse practitioners and physician assistants
      in survivorship care.
AB  - The number of cancer survivors in the United States now approaches 12 million
      individuals, with an estimated 7.2% of the general population aged 18 years or
      older reporting a previous cancer diagnosis. These figures highlight a number of
      questions about the care of survivors-how patients at risk for a known set of
      health problems should be followed, by whom, and for how long. At the same time
      that oncologists are developing strategies to provide services to this growing
      population, there are economic and systems challenges that have relevance to the
      previous questions, including a predicted national shortage of physicians to
      provide oncology services. Nurse practitioners (NPs) and physician assistants
      (PAs) have been identified as members of the health care team who can help reduce
      the oncology supply and demand gap in a number of ways. The ASCO Study of
      Collaborative Practice Arrangements (SCPA) in 2011 concluded that oncology
      patients were aware and satisfied when their care was provided by NPs and PAs;
      there was an increase in productivity in practices that utilized NPs and PAs;
      utilizing the full scope of practice of NPs and PAs was financially advantageous;
      and, physicians, NPs, and PAs are highly satisfied with their collaborative
      practices. Increasingly, the oncology and health policy literature contains
      evidence supporting innovative provider models. There is still much work to be
      done to move beyond pilot data to establish the true value of these models. 

PMID- 24451833
TI  - Driving Evidence-Based Standardization of Care within a Framework of Personalized
      Medicine.
AB  - Cancer care in the United States faces a number of key challenges today that are
      causing payers, referring physicians, and patients alike to question the value of
      the care, in terms of both outcomes and costs. New technologies in the form of
      pharmaceuticals and biologics, prognostic tests, and new radiation therapy tools
      and techniques offer the promise of improved outcomes, but their cost
      effectiveness is often unclear. Oncologists themselves are caught in the middle,
      as they are the prescribers of such technologies and the entity billing for such
      services but have only limited ability to influence the pricing models for these
      services. Finally, as oncology care becomes more complex because of increased
      understanding of the pathogenesis of the many subtypes of cancer, the community
      based oncologist who cares for patients with all cancer subtypes is confronted
      with maintaining an up-to-date knowledge base that is expanding rapidly. Although
      no single solution for these issues exists in oncology today, the experience at
      the University of Pittsburgh Medical Center has demonstrated that a clinical
      pathways program can reduce unwarranted variability in both treatment and
      outcomes, drive adherence to evidence-based medicine, and, in the process, reduce
      the growth rate in the total costs of cancer care. 

PMID- 24451834
TI  - The future of oncology care with personal health records.
AB  - Personal health records (PHRs) and patients' access to their own clinical
      information through a patient portal are changing the patient-physician
      relationship. Historically, health care providers have been gatekeepers of
      patients' medical records. Now, these portals provide patients access to clinical
      information, electronic messaging with the clinical team, and appointment and
      billing information. This type of access supports patient empowerment by engaging
      patients in their own care. Patients desire online access to information. The
      health care industry, like any other, must respond to the needs of its consumers.
      Oncology practices face unique challenges to meeting this need because of the
      complex nature of medical records of patients with cancer. Health care providers
      worry about the consequences of patients receiving "bad news" online, thereby
      increasing patient anxiety. This anxiety may, in turn, increase providers'
      workload by creating additional calls or visits to the office. These valid
      concerns require careful consideration when implementing a PHR or patient portal
      into a practice. Providers will benefit from a clear understanding of actual
      compared with potential risks and benefits. Much of the concerns about the
      negative effect on providers' workload and the potential increase in patients'
      anxiety have not been borne out. On the other hand, the implementation strategy,
      governance structure, and end-user education are crucial components to ensuring
      success. Successful implementation of a PHR or patient portal affords the
      opportunity to improve patient satisfaction and increase efficiency in provider
      workflow. The possibility exists to improve patient outcomes by engaging the
      patient in decision making and follow through. 

PMID- 24451835
TI  - Measuring and Improving Value of Care in Oncology Practices: ASCO Programs from
      Quality Oncology Practice Initiative to the Rapid Learning System.
AB  - Rising cancer care costs are no longer sustainable. Medical oncologists must
      focus on providing the maximum value to their patients; improving short-term,
      intermediate and long-term outcomes; and managing overall costs. Accurate
      measurement of outcomes and overall cost is essential to informing providers and
      institutions and in the quest for continuous improvement in value. The ASCO
      Quality Oncology Practice Initiative (QOPI) is an excellent tool for sampling
      processes of care in medical oncology practices. To achieve the larger goal of
      improving the value of cancer care, ASCO is investing in the development of a
      Rapid Learning System, which will leverage emerging information technologies to
      more accurately measure outcomes (including those reported by the patient) and
      costs, resulting in highly efficient, effective, and safe cancer care. 

PMID- 24451836
TI  - Buoyancy: A Model for Self-Reflection about Stress and Burnout in Oncology
      Providers.
AB  - Burnout is a prevalent syndrome among oncology providers marked by exhaustion, a
      sense of ineffectiveness, and depersonalization. This syndrome can have enormous
      influence on patient care as well as the provider's career fulfillment and
      personal and family well-being. A buoyancy model is proposed as a method to take
      stock of key parameters that may contribute to happiness and resiliency. Self
      monitoring of personal buoyancy parameters may help oncology providers prevent
      burnout. 

PMID- 24451837
TI  - Encountering grief in patient care.
AB  - Grief is essentially unavoidable and is a normal reaction to loss. Grief may be
      experienced by patients and their loved ones as well as by physicians and members
      of the health care team in response to the consequences of illness or death.
      Grief is typified by certain indicators that may significantly effect one's
      emotional and physical well-being. Although these indicators tend to follow a
      general pattern, there is variability among individuals. Complicated grief may
      require psychiatric intervention. Caring for the seriously ill or dying patient
      may be particularly challenging from an emotional level and may increase the risk
      of burnout. Recognition of these emotions is a critical aspect of providing
      compassionate care on a sustainable level. Various strategies may be beneficial
      in coping with grief, and the exploration of grief may provide greater insight
      into the humanistic basis of medicine. 

PMID- 24451838
TI  - New insights in cross-cultural communication.
AB  - Improving clinician-patient communication, improving clinical decision making,
      and eliminating mistrust have been identified as three key areas for reducing
      disparities in care. An important step is the training of cancer professionals to
      deliver culturally competent care in clinical settings as well as increasing the
      proportion of underrepresented minorities in the health care workforce. Providing
      care that is attuned to the patient's cultural preferences begins by talking to
      the patient about his or her cultural history and identifying the locus of
      decision making, preferences for disclosure of vital health information, and
      goals of care. Patients with low literacy and those with poor fluency of the
      dominant language require additional services. Language interpretation by trained
      professionals is fundamental to ensure that patients are able to provide informed
      consent for treatment. A working definition of culture involves multiple
      dimensions and levels and must be viewed as both dynamic and adaptive, rather
      than simply as a collection of beliefs and values. Effective cross-cultural
      education avoids stereotyping and promotes communication and negotiation to solve
      problems and minimize tension and conflict. Recent research has identified that
      unconscious biases held by clinicians affect their behavior and recommendations
      for treatment. 

PMID- 24451839
TI  - Patients with cancer, internet information, and the clinical encounter: a
      taxonomy of patient users.
AB  - The Internet has changed all of our lives forever and has certainly changed the
      way in which patients acquire information, share their stories, find others in
      similar circumstances, and analyze their medical situations. It is very clear
      that patients have widely adopted the use of online resources in the face of
      illness. Access to unfiltered information online clearly has positive and
      negative potential effects, and the introduction of Internet information into the
      physician-patient encounter may be managed in more or less productive ways. The
      means of managing such introductions of information should vary based on
      physicians' analyses of patients' information preferences and styles and their
      apparent reactions to the information. Managed well, knowledgeable patients can
      offer important opportunities of informed and shared decision making. 

PMID- 24451840
TI  - A Balanced Approach to Physician Responsibilities: Oncologists' Duties toward
      Themselves.
AB  - Although critical to the provision of best patient care, physician self-care is
      an underattended aspect of responsibility in the medical professions, including
      oncology. Neglecting self-care bears negative consequences for the individual
      oncologist, ranging from burnout and fatigue to interpersonal and relationship
      stress, addiction, and disruptive behavior. It may also contribute to medical
      errors, disinterest in or depersonalization of patient care, and lower quality of
      care. Because of its effect on physicians, patients, and the health care
      environment, physician self-care is increasingly recognized as an important
      professional responsibility. Nonetheless, professional obligations, competing
      demands on time, and personal priorities conspire to prevent a large proportion
      of oncologists from adequately attending to self-care in even simple ways, such
      as getting sufficient exercise and sleep. This chapter discusses the need for
      physician self-care and the repercussions of not meeting this fundamental
      responsibility. Self-care is described in the context of three life domains:
      professional, personal (physical, psychological, mental, and spiritual), and
      interpersonal (relationships, family, social, and community). Strategies are
      provided for caring for the self in each domain. 

PMID- 24451841
TI  - PI3 Kinase in Cancer: From Biology to Clinic.
AB  - The discovery and clinical development of small-molecule inhibitors of the
      phosphatidylinositide 3-kinase (PI3 kinase) family of lipid kinases have marked a
      remarkable 20-year journey that follows the progressive developments in cancer
      biology over the last few decades: from hypothesis-driven, basic cancer research
      that began with viral oncogenesis and developed in the 1960s and 70s, through the
      discovery of individual mutated oncogenes and tumor suppressor genes in 1970 and
      80s and the linkage of these cancer genes to signal transduction pathways in the
      1990s, to all large-scale genome-wide sequencing, functional screening, and
      network biology efforts today. Thus, PI3 kinase research began with the discovery
      in 1985 of a new type of enzyme activity associated with viral oncogenesis. It
      benefited greatly from the discovery of wortmannin and LY294002 as PI3 kinase
      inhibitors and chemical tools in late 1980s to mid-90s. Alongside these tools,
      genetic validation of PI3 kinase as a target initially involved activation by
      upstream oncogenic receptor tyrosine kinases and RAS mutation, together with
      overexpression and amplification of the p110alpha catalytic isoform of PI3 kinase
      and frequent loss of the tumor suppressor and negative regulator of PI3 kinase
      activity, PTEN. As PI3 kinase drug development began, further stimulus came from
      the discovery through genome sequencing of mutations in PIK3CA, which encodes
      p110alpha and is the most frequently mutated kinase in the human genome. From
      these beginnings, there are now many PI3 kinase inhibitors in clinical trials and
      more in preclinical development. We review progress, current challenges, and
      future opportunities in this article. 

PMID- 24451842
TI  - Urinary concentrations of 2,4-dichlorophenol and 2,5-dichlorophenol in the U.S.
      population (National Health and Nutrition Examination Survey, 2003-2010): trends
      and predictors.
AB  - BACKGROUND: 2,4-Dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), and their
      precursors are widely used in industry and in consumer products. Urinary
      concentrations of these dichlorophenols (DCPs) have been measured as part of four
      National Health and Nutrition Examination Survey (NHANES) cycles in order to
      assess the exposure to these compounds or their precursors among the general U.S.
      population. OBJECTIVES: We identified predictors and evaluated trends in DCP
      concentrations according to race/ethnicity, age, sex, family income, and housing
      type. METHODS: We used analysis of covariance to examine associations of various
      demographic parameters and survey cycle with urinary concentrations of DCPs
      during NHANES 2003-2010. We also conducted weighted logistic regressions to
      estimate associations of DCP concentrations above the 95th percentile with
      housing type, race/ethnicity, and income. RESULTS: We detected DCPs in at least
      81% of participants. Geometric mean (GM) urinary concentrations were higher for
      2,5-DCP (6.1-12.9 MUg/L) than 2,4-DCP (0.8-1.0 MUg/L) throughout 2003-2010.
      Adjusted GM concentrations of the DCPs among children (6-11 years of age) and
      adults > 60 years of age were higher than among adolescents and other adults.
      Adjusted GM concentrations among non-Hispanic whites were lower than among non
      Hispanic blacks and Mexican Americans, although differences according to
      race/ethnicity were less pronounced among participants in high-income households.
      Among non-Hispanic blacks and Mexican Americans, adjusted GM concentrations were
      lowest among high-income participants relative to other income groups, with a
      monotonic decrease with increasing income among Mexican Americans. Type of
      housing and race/ethnicity were significant predictors of DCP urinary
      concentrations above the 95th percentile. Furthermore, urinary DCP concentrations
      have showed a downward trend since 2003. CONCLUSIONS: Exposure to DCPs and their
      precursors was prevalent in the general U.S. population in 2003-2010. We
      identified age and race/ethnicity, family income, and housing type as predictors
      of exposure to these compounds.

PMID- 24451843
TI  - Deoxynivalenol: a major player in the multifaceted response of Fusarium to its
      environment.
AB  - The mycotoxin deoxynivalenol (DON), produced by several Fusarium spp., acts as a
      virulence factor and is essential for symptom development after initial wheat
      infection. Accumulating evidence shows that the production of this secondary
      metabolite can be triggered by diverse environmental and cellular signals,
      implying that it might have additional roles during the life cycle of the fungus.
      Here, we review data that position DON in the saprophytic fitness of Fusarium, in
      defense and in the primary C and N metabolism of the plant and the fungus. We
      combine the available information in speculative models on the role of DON
      throughout the interaction with the host, providing working hypotheses that await
      experimental validation. We also highlight the possible impact of control
      measures in the field on DON production and summarize the influence of abiotic
      factors during processing and storage of food and feed matrices. Altogether, we
      can conclude that DON is a very important compound for Fusarium to cope with a
      changing environment and to assure its growth, survival, and production of toxic
      metabolites in diverse situations. 

PMID- 24451844
TI  - Active immunity induced by passive IgG post-exposure protection against ricin.
AB  - Therapeutic antibodies can confer an instant protection against biothreat agents
      when administered. In this study, intact IgG and F(ab')2 from goat anti-ricin
      hyperimmune sera were compared for the protection against lethal ricin mediated
      intoxication. Similar ricin-binding affinities and neutralizing activities in
      vitro were observed between IgG and F(ab')2 when compared at the same molar
      concentration. In a murine ricin intoxication model, both IgG and F(ab')2 could
      rescue 100% of the mice by one dose (3 nmol) administration of antibodies 1 hour
      after 5 * LD50 ricin challenge. Nine days later, when the rescued mice received a
      second ricin challenge (5 * LD50), only the IgG-treated mice survived; the
      F(ab')2-treated mice did not. The experimental design excluded the possibility of
      residual goat IgG responsible for the protection against the second ricin
      challenge. Results confirmed that the active immunity against ricin in mice was
      induced quickly following the passive delivery of a single dose of goat IgG post
      exposure. Furthermore, it was demonstrated that the induced active immunity
      against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy
      not only provides immediate protection to the victim after ricin exposure, but
      also elicits an active immunity against ricin that subsequently results in long
      term protection. 

PMID- 24451845
TI  - Effects of bread making and wheat germ addition on the natural deoxynivalenol
      content in bread.
AB  - Deoxynivalenol (DON, vomitoxin) is a type-B trichothecene mycotoxin produced by
      several field fungi such as Fusarium graminearum and Fusarium culmorum and known
      to have various toxic effects. This study investigated the effect of the bread
      making process on the stability of DON in common bread and wheat germ-enriched
      bread using naturally contaminated ingredients at the level of 560 ug/kg. The
      concentration of DON and its evolution during bread making were determined by
      immunoaffinity column cleanup followed by liquid chromatography with diode array
      detection (HPLC-DAD). During the bread making process, DON was reduced by 2.1%
      after fermentation and dropped by 7.1% after baking, reaching a maximum reduction
      of 19.8% in the crust as compared with a decrease of 5.6% in the crumb. The
      addition of 15% wheat germ to the dough did not affect DON stability during bread
      making, showing an apparent increase of 3.5% after fermentation and a reduction
      by 10.2% after baking. 

PMID- 24451848
TI  - Plasmonic-cavity model for radiating nano-rod antennas.
AB  - In this paper, we propose the analytical solution of nano-rod antennas utilizing
      a cylindrical harmonics expansion. By treating the metallic nano-rods as
      plasmonic cavities, we derive closed-form expressions for both the internal and
      the radiated fields, as well as the resonant condition and the radiation
      efficiency. With our theoretical model, we show that besides the plasmonic
      resonances, efficient radiation takes advantage of (a) rendering a large value of
      the rods' radius and (b) a central-fed profile, through which the radiation
      efficiency can reach up to 70% and even higher in a wide frequency band. Our
      theoretical expressions and conclusions are general and pave the way for
      engineering and further optimization of optical antenna systems and their
      radiation patterns. 

PMID- 24451847
TI  - Interplay between phosphoinositide lipids and calcium signals at the leading edge
      of chemotaxing ameboid cells.
AB  - The chemotactic migration of eukaryotic ameboid cells up concentration gradients
      is among the most advanced forms of cellular behavior. Chemotaxis is controlled
      by a complex network of signaling proteins bound to specific lipids on the
      cytoplasmic surface of the plasma membrane at the front of the cell, or the
      leading edge. The central lipid players in this leading edge signaling pathway
      include the phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), both of
      which play multiple roles. The products of PI(4,5)P2 hydrolysis, diacylglycerol
      (DAG) and Ins(1,4,5)P3 (IP3), are also implicated as important players. Together,
      these leading edge phosphoinositides and their degradation products, in concert
      with a local Ca(2+) signal, control the recruitment and activities of many
      peripheral membrane proteins that are crucial to the leading edge signaling
      network. The present critical review summarizes the current molecular
      understanding of chemotactic signaling at the leading edge, including newly
      discovered roles of phosphoinositide lipids and Ca(2+), while highlighting key
      questions for future research. 

PMID- 24451849
TI  - Reactive oxygen species mediate pollen tube rupture to release sperm for
      fertilization in Arabidopsis.
AB  - In flowering plants, sperm are transported inside pollen tubes to the female
      gametophyte for fertilization. The female gametophyte induces rupture of the
      penetrating pollen tube, resulting in sperm release and rendering them available
      for fertilization. Here we utilize the Arabidopsis FERONIA (FER) receptor kinase
      mutants, whose female gametophytes fail to induce pollen tube rupture, to
      decipher the molecular mechanism of this critical male-female interactive step.
      We show that FER controls the production of high levels of reactive oxygen
      species at the entrance to the female gametophyte to induce pollen tube rupture
      and sperm release. Pollen tube growth assays in vitro and in the pistil
      demonstrate that hydroxyl free radicals are likely the most reactive oxygen
      molecules, and they induce pollen tube rupture in a Ca(2+)-dependent process
      involving Ca(2+) channel activation. Our results provide evidence for a RHO
      GTPase-based signalling mechanism to mediate sperm release for fertilization in
      plants. 

PMID- 24451850
TI  - Dental implant cone beam scans of older individuals often reveal potentially life
      threatening atherosclerotic disease.

PMID- 24451851
TI  - Comparison of osseointegration on various implant surfaces after bacterial
      contamination and cleaning: a rabbit study.
AB  - PURPOSE: To examine the osseointegration of various implant surfaces after
      bacterial contamination and cleaning. MATERIALS AND METHODS: Four types of
      implant surface were manufactured: machined (M); plasma-spray hydroxyapaptite
      (HA); sandblasted, large-grit, acid-etched (SA); and titanium anodic oxide (TAO)
      were manufactured. The surface characteristics of these implants were determined
      using a scanning electron microscope, an energy dispersive spectrometer, and a
      contact profilometer. Each surface was subdivided into control and test groups.
      Test implants were co-incubated with Prevotella intermedia for 2 weeks, then
      cleaned with cotton pellets, soaked in saline, and irrigated. Control implants
      underwent the same cleaning procedure, but without bacterial contamination. Four
      control or test implants with different surface types were randomly inserted into
      the tibia of 10 New Zealand white rabbits. After 6 weeks of healing, 5 rabbits
      were sacrificed for histomorphometry, and the rest for removal torque assay.
      RESULTS: Bacterial contamination adversely influenced every implant surface in
      terms of bone-to-implant contact (BIC) ratio and required removal torque. The
      negative results reached significant levels for rougher surfaces (HA and SA). For
      both contaminated and uncontaminated samples, HA and SA implants required
      significantly higher removal torque than that required for M implants.
      CONCLUSION: Bacterial contamination jeopardized osseointegration on every tested
      implant surface. A more negative effect on BIC was found for implants with
      rougher surfaces. However, contaminated rough-surfaced implants showed more
      removal torque resistance than contaminated smooth implants.

PMID- 24451852
TI  - A novel method to evaluate the neurocompatibility of dental implants.
AB  - PURPOSE: To evaluate the neurocompatibility of different types of dental implant
      surface treatments using the P19 neural cell line. MATERIALS AND METHODS: P19
      cells were plated and supplemented with retinoic acid to grow as aggregates for 4
      days. Twenty dental implants were selected from four different implant systems
      with five different surface treatments. The implants were divided into four
      groups (n=5), placed inside medical rings, and fixed by injection of warm gutta
      percha using a thermoplastic injection technique. Implant molds were placed
      inside graded culture dishes, and culture medium containing P19 neural cells were
      plated on the dishes for 4 days. After 24 hours, the surfaces of the implant
      molds were covered with self-curing resin to make a replica of each mold surface.
      Replicas were assessed under a scanning electron microscope, and the number of
      cells and the total cells covering the areas were evaluated. Data were analyzed
      by a post hoc Tukey test. RESULTS: There were significant differences in P19 cell
      counts between all modified and electropolished surfaces. The highest P19 cell
      counts were shown on OsseoSpeed and Laser-Lok surfaces. The lowest counts were
      shown on the Nanotite surface at the collar. OsseoSpeed and Laser-Lok surfaces
      showed higher counts at the collar than on the body; the opposite was seen for
      SLActive and Nanotite surfaces. Cell-covered areas on Laser-Lok surfaces showed
      significantly higher values than the resorbable blasted media (RBM)-treated
      surfaces, while it was not significantly different from the OsseoSpeed surface of
      collar regions. SLActive collar regions showed larger cell-covered areas than the
      SLActive body surfaces, but this was not significant. CONCLUSIONS: All test
      surface treatments in this study showed better neurocompatibility than control
      group surfaces. The Laser-Lok, RBM, and OsseoSpeed surfaces were superior to the
      Nanotite and SLActive surfaces in terms of neurocompatibility.

PMID- 24451853
TI  - Evaluation of bone heating, drill deformation, and drill roughness after implant
      osteotomy: guided surgery and classic drilling procedure.
AB  - PURPOSE: This study evaluated and compared bone heating, drill deformation, and
      drill roughness after several implant osteotomies in the guided surgery technique
      and the classic drilling procedure. MATERIALS AND METHODS: The tibias of 20
      rabbits were used. The animals were divided into a guided surgery group (GG) and
      a control group (CG); subgroups were then designated (G0, G1, G2, G3, and G4,
      corresponding to drills used 0, 10, 20, 30 and 40 times, respectively). Each
      animal received 10 sequential osteotomies (5 in each tibia) with each technique.
      Thermal changes were quantified, drill roughness was measured, and the drills
      were subjected to scanning electron microscopy. RESULTS: Bone temperature
      generated by drilling was significantly higher in the GG than in the CG. Drill
      deformation in the GG and CG increased with drill use, and in the CG a
      significant difference between G0 and groups G3 and G4 was observed. In the GG, a
      significant difference between G0 and all other groups was found. For GG versus
      CG, a significant difference was found in the 40th osteotomy. Drill roughness in
      both groups was progressive in accordance with increased use, but there was no
      statistically significant difference between subgroups or between GG and CG
      overall. CONCLUSION: During preparation of implant osteotomies, the guided
      surgery technique generated a higher bone temperature and deformed drills more
      than the classic drilling procedure. The increase in tissue temperature was
      directly proportional to the number of times drills were used, but neither
      technique generated critical necrosis-inducing temperatures. Drill deformation
      was directly proportional to the number of times the drills were used. The
      roughness of the drills was directly proportional to the number of reuses in both
      groups but tended to be higher in the GG group.

PMID- 24451854
TI  - The effect of abutment screw length on screw loosening in dental implants with
      external abutment connections after thermocycling.
AB  - PURPOSE: The aim of this study was to investigate the effects of abutment screw
      length on screw loosening after thermocycling. MATERIALS AND METHODS: Twenty-one
      grade 5 titanium (Ti) abutments were connected to grade 4 Ti implants with grade
      5 Ti abutment screws. These implant/abutment screw/abutment assemblies were
      divided into seven groups according to the length of the abutment screw; each
      group included three assemblies. The screws were tightened to 30 Ncm and
      subjected to 2,000 thermocycles in water baths at 4 degrees C and 60 degrees C,
      with 60 seconds of immersion at each temperature. Removal torque values (RTVs)
      were measured before and after thermocycling, and differences in RTVs according
      to abutment screw length pre- and post-thermocycling were analyzed statistically.
      RESULTS: Mean RTVs before and after thermocycling were as follows: 23.0+/-4.4 Ncm
      and 25.5+/-0.9 Ncm for 1.4-mm-long abutment screws, 26.7+/-2.5 and 24.5+/-2.6 Ncm
      for 1.8-mm screws, 26.0+/-1.3 and 25.0+/-1.8 for 2.2-mm screws, 25.0+/-2.0 and
      25.3+/-0.8 for 2.6-mm screws, 22.5+/-4.4 and 22.5+/-0.5 for 3.0-mm screws, 26.5+/
      2.3 and 25.2+/-1.3 for 3.4-mm screws, and 25.5+/-4.8 and 23.2+/-0.8 for 3.8-mm
      screws, respectively. As the screw length increased, no statistically significant
      differences were found in the mean RTVs among the groups before or after
      thermocycling. Additionally, none of the groups showed significant changes in
      RTVs after cyclic thermal stress. CONCLUSION: Abutment screw length had no
      significant effect on screw loosening under thermal stress. From the results of
      this study, daily temperature changes in the oral cavity may have no negative
      influence on the integrity of an implant-abutment joint when a minimum of three
      and a half threads of an abutment screw are engaged.

PMID- 24451855
TI  - Biologic response to titanium implants with laser-treated surfaces.
AB  - PURPOSE: To examine the biologic response to titanium implant surfaces treated
      with a neodymium:yttrium-aluminum-garnet laser. MATERIALS AND METHODS: Sixty mini
      implants made of grade 2 titanium were placed in the femora of 30 Wistar rats.
      Thirty implants had a machined surface and the other 30 had surfaces that were
      roughened by laser treatment. The animals were subdivided into three groups
      according to bone repair periods of 15, 30, and 60 days. The samples were
      observed under light and electron scanning microscopes and analyzed with the
      Student t test. RESULTS: Formation of new bone trabeculae toward the surface was
      apparent for the laser-treated implants at 15 days. Thin layers of bone matrix in
      intimate contact with the surface in the area of the central screw threads were
      observed, indicating high biocompatibility. Similar results were seen with
      machined implants after 30 days. A significant difference in bone formation was
      observed between the implant types at 15 days. CONCLUSION: Bone-to-implant
      contact was better on the surfaces subjected to laser treatment than on the
      machined titanium implants. The development of new laser treatments, which
      promote alterations in the surface energy as well as in the macro- and
      microstructures of titanium, may lead to improved bone-to-implant contact and
      thus better outcomes.

PMID- 24451856
TI  - Assessment of the visibility and characteristics of the mandibular incisive
      canal: cone beam computed tomography versus panoramic radiography.
AB  - PURPOSE: The aim of this study was to assess and compare the visibility,
      diameter, and course of the mandibular incisive canal (MIC) using cone beam
      computed tomography (CBCT) and panoramic radiography. MATERIALS AND METHODS: CBCT
      images and panoramic radiographs from 243 patients were used in this study.
      Standard exposure and patient positioning protocols were used for all the
      patients. Both types of images were assessed by two dentomaxillofacial
      radiologists. The diameter and the endpoint level of the MIC were measured using
      the CBCT images. Statistical analysis was performed using t tests in statistical
      software. RESULTS: Of the 486 hemimandibles examined, the MIC was visible in 249
      (51.2%) radiographs and 459 (94.4%) CBCT images. The mean diameters of the MICs
      were 1.91+/-0.45 mm on the right side and 1.94+/-0.41 mm on the left side. The
      MICs on both the right and left sides of the mandible showed statistically
      significant differences in diameter in male versus female patients. The
      visibility of the MIC on the panoramic radiographs according to the increase in
      the diameter was not statistically significant for both sides. Twenty MICs
      reached to the midline of the mandible, and the majority of the MICs (n=114)
      terminated between the canine and the first premolar. CONCLUSION: The visibility
      of the MIC in CBCT is much better than that observed in conventional panoramic
      radiography. Even some large MICs could not be observed in panoramic radiographs.
      Detection of the MIC using CBCT may be crucial for surgical procedures involving
      the interforaminal region.

PMID- 24451857
TI  - Peri-implant bone loss around single and multiple prostheses: systematic review
      and meta-analysis.
AB  - PURPOSE: The objective of this systematic review and meta-analysis was to assess
      and compare the marginal bone loss around implants supporting single fixed
      prostheses and multiple-unit screw-retained prostheses. MATERIALS AND METHODS:
      The literature was searched manually and electronically to identify studies in
      which the marginal peri-implant bone loss around single-implant prostheses and
      screw-retained multiple-implant prostheses was evaluated radiographically. Two
      reviewers independently selected the literature and extracted the data. The
      random-effects method was used to obtain estimates of marginal peri-implant bone
      loss (means and 95% confidence intervals [CIs]). RESULTS: Of the 2,107 studies
      identified by a preliminary search, 17 fulfilled the inclusion criteria; 7 were
      related to single-implant prostheses and 10 to multiple-implant screw-retained
      fixed prostheses. The mean marginal peri-implant bone loss was 0.9 mm (95% CI,
      0.49 to 1.32 mm) for multiple-implant screw-retained prostheses and 0.58 mm (95%
      CI, 0.37 to 0.80 mm) for single-implant prostheses. CONCLUSION: This indirect
      comparison provided no evidence to support the assertion that there are
      differences in marginal peri-implant bone loss between single implant prostheses
      and multiple screw-retained prostheses.

PMID- 24451858
TI  - Loss of preload in screwed implant joints as a function of time and
      tightening/untightening sequences.
AB  - PURPOSE: The purpose of this study was to determine whether abutment screw
      tightening and untightening influenced loss of preload in three different
      implant/abutment interfaces, or on the implant body. MATERIALS AND METHODS: Five
      custom-fabricated machined titanium implants were used, each with its respective
      abutment, with different connection types, retention screws, and torque values
      (external hexagon with titanium screw/32 Ncm, external hexagon with coated
      screw/32 Ncm, internal hexagon/20 Ncm and internal conical/20 and 32 Ncm). Each
      implant tested had two strain gauges attached and was submitted to five
      tightening/untightening sequences. RESULTS: External hexagons resulted in the
      lowest preload values generated in the implant cervical third (mean of 27.75 N),
      while the internal hexagon had the highest values (mean of 219.61 N).
      CONCLUSIONS: There was no immediate significant loss of preload after screw
      tightening. Tightening/untightening sequences, regardless of the implant/abutment
      interface design or type of screw used in the study, did not result in any
      significant loss of initial preload. Conical implant connections demonstrated
      greater structural reinforcement within the internal connections.

PMID- 24451859
TI  - Integrity of implant surface modifications after insertion.
AB  - PURPOSE: The surface integrity associated with implant placement was examined to
      determine whether the topography of common implant surface modifications is
      retained after implant insertion. MATERIALS AND METHODS: Turned (TU), acid-etched
      (AE), and anodized (AN) experimental implants prepared in-house were inserted
      into polyurethane foam blocks using a standard drilling protocol at maximum
      torque of 37 Ncm. Qualitative analysis of the surfaces of preinserted and
      postinserted implants was done by scanning electron microscopy (SEM), and
      quantitative analysis of the implant threads was performed by interferometry.
      Among the roughness parameters calculated were average height deviation (Sa),
      peak height above core roughness (Spk), and maximum peak height (Sp). RESULTS:
      SEM showed that TU implants exhibited similar morphology before and after implant
      insertion. The AE implants showed reduced peak height associated with flattened
      areas after insertion. AN implants demonstrated the most extensive damage
      associated with insertion; the entire porous oxide layer had been removed at the
      apical region and on the crests of the threads. Surface roughness evaluation was
      corroborated with the SEM findings. Roughness parameters were similar for TU
      implants, and reduced Sp and Spk values were observed for the AE implants after
      insertion. AN implants were more complex to measure quantitatively because of
      variations in the extent of damage to the oxide layer during insertion. In some
      cases, the AN layer had been completely removed, exposing the underlying material
      and clearly decreasing the roughness, and in other cases it remained intact and
      rough. Polyurethane foam blocks in contact with AN implants demonstrated loose
      titanium particles of different sizes. CONCLUSION: This preliminary study
      demonstrated surface damage after insertion of experimental anodized implants
      into polyurethane blocks associated with loose titanium particles at the
      interface. Future in vivo studies should investigate the relevance of such loose
      particles on the peri-implant bone response.

PMID- 24451860
TI  - Influence of simulated bone quality and cortical bone thickness on implant
      stability detection using resonance frequency and damping factor analysis.
AB  - PURPOSE: The aim of this study was to test whether damping factor is an adequate
      parameter for monitoring the status of the trabecular bone-implant interface.
      MATERIALS AND METHODS: Implants were placed in epoxy resin with elastic moduli of
      2,900, 210, and 1.4 MPa to simulate cortical bone, cancellous bone, and
      connective tissue, respectively. Resonance frequency and damping factor (DF)
      values of the tested implants were measured using vibration analysis. An impulse
      force was used to induce vibration within implants. The DF values of the tested
      implants were calculated from the obtained frequency spectrum using a half-power
      method. The resulting data were analyzed to test the statistical effects of the
      cortical height and trabecular status on the DF values of the sample implants.
      RESULTS: When the simulated tissue at the implant-bone interface changed from
      connective tissue to bone, the detected DF value decreased markedly. In addition,
      the mean DF value of the tested implants increased significantly (P<.05) from
      0.043+/-0.008 when the elastic modulus of the surrounding resins was 2,900 MPa to
      0.114+/-0.018 when the modulus was 1.4 MPa. Furthermore, when the tested implants
      were firmly fixed with 2 mm of simulated cortical bone, the alternation of
      healing tissue at the trabecular bone area could be detected by the DF method.
      CONCLUSION: DF is a sensitive measure for monitoring the status of oral implant
      osseointegration when implant boundary conditions are good at the cortical level
      but still weak at the trabecular bone area.

PMID- 24451861
TI  - Evaluation of UCLA implant-abutment sealing.
AB  - PURPOSE: To evaluate the effect of the presence of a prefabricated cobalt
      chromium (CoCr) margin in a universal castable long abutment (UCLA) on the
      sealing capability and fit of the implant-abutment interface. MATERIALS AND
      METHODS: One-hundred twenty external hexagon implants (SIN) were divided into two
      groups (n=60 each) to receive UCLA abutments from six manufacturers (n=10 each)
      either with or without a CoCr margin (n=60 each). Abutments were cast and 12
      groups were formed: M (Microplant), I (Impladen), S (SIN), Sv (Signo Vinces), T
      (TitaniumFix), and B (Bionnovation). Sealing was determined by placing 0.7 uL of
      0.1% toluidine blue in the implant wells before abutment torquing. Implant
      abutment samples were placed into 2.0-mL vials containing 0.7 mL of distilled
      water to maintain the implant-abutment interface, and aliquots of 100 uL of water
      were retrieved at 1, 3, 6, 24, 48, 72, 96, and 144 hour incubation times for
      measurement of absorbance in a spectrophotometer, and returned for repeated
      measurements. Two-way ANOVA (P<.05) and Tukey's test were used. Scanning electron
      microscopy (SEM) was used for observation of the implant-abutment fit. RESULTS:
      Groups M, Sv, and T without the CoCr margin resulted in complete release of
      toluidine blue at 1 hour, whereas I, S, and B did so at 3, 24, and 96 hours,
      respectively. Complete leakage in abutments with the prefabricated margin
      occurred at 6 hours for S; 24 hours for Sv, T, and B; and 72 hours for M and I.
      Implant-abutment gaps were observed in all groups. A poorer fit was depicted for
      groups M and T without the CoCr margin. CONCLUSION: Complete leakage was observed
      for all UCLA abutments regardless of the presence of the CoCr margin. Implant
      abutment gaps were observed in all groups.

PMID- 24451862
TI  - In vivo effectiveness of silicone gel sheets as barriers at the inner microgap
      between a prosthetic abutment and an external-hexagon implant platform.
AB  - PURPOSE: Bacterial penetration and colonization of the microgap at the implant
      abutment interface have been reported in several studies. The aim of this study
      was to evaluate the effectiveness of placing a silicone membrane between the
      abutment and the implant platform in an attempt to seal the interface. MATERIALS
      AND METHODS: A total of 15 external-hex implants were placed in 10 patients with
      clinically healthy peri-implant tissues, and all of the patients had ceramic
      prosthetic crowns. Samples were collected from the microgaps before, 30 days
      after, and 90 days after insertion of a silicone membrane. Bacterial DNA was
      extracted and submitted in triplicate to polymerase chain reaction using primers
      specific for four peri-implant pathogens: Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia.
      RESULTS: In the initial samples, a positivity of 52% was found, which was
      different from that found in samples collected after 30 days (32%) and 90 days
      (27%) after insertion of the membrane. CONCLUSION: It was evident that the
      silicone membrane reduced, but did not prevent, penetration of these species into
      external-hex implants.

PMID- 24451863
TI  - Gingival margin changes in maxillary anterior sites after single immediate
      implant placement and provisionalization: a 5-year retrospective study of 47
      patients.
AB  - PURPOSE: To evaluate gingival margin changes in the esthetic zone after immediate
      implant placement and provisionalization over 5 years with a custom anatomic
      provisional abutment. MATERIALS AND METHODS: Single maxillary incisor immediate
      implant placement and provisionalization procedures, completed and followed
      between February 2006 and August 2006, were analyzed retrospectively. During
      clinical recalls at 3 months, 1 year, and 5 years, changes in gingival margins
      were recorded with clinical photographs and recorded in millimeters. RESULTS:
      Forty-seven patients each received a single implant (19 central incisors, 28
      lateral incisors) and were followed for 5 years. Implants and restorations had a
      100% survival rate during the study. The mean gingival margin changes (recession)
      were 0.17 mm at the time of definitive restoration, 0.27 mm at 3 months, 0.30 mm
      at 1 year, and 0.30 mm at 5 years. After 5 years, 24 of the 47 implant crowns had
      no significant gingival recession. All central incisor sites received 4.3-mm
      diameter implants and had a mean change in tooth length of 0.03 mm at 5 years.
      Lateral incisor sites (n=28) received either a 3.5-mm-diameter implant (n=20) or
      a 4.3-mm-diameter implant (n=8). Lateral sites with the 3.5-mm implant had a mean
      change in gingival margin height of 0.08 mm of tooth length at 5 years; lateral
      sites with a 4.3-mm platform displayed a mean change of 0.82 mm of tooth length.
      CONCLUSION: This study suggests that implant diameter, gingival biotype, surgical
      technique, and/or the reason for tooth loss can influence the amount of gingival
      recession occurring over 5 years. Most recession occurred within the first 3
      months, between implant placement/provisionalization and definitive restoration.
      The use of a customized anatomic provisional abutment can reduce the amount and
      frequency of recession.

PMID- 24451864
TI  - Mandibular ridge expansion using a horizontal bone-splitting technique and
      synthetic bone substitute: an alternative to bone block grafting?
AB  - PURPOSE: Inadequate bone width in atrophic edentulous jaws is a challenge for
      successful oral rehabilitation with endosseous dental implants. The aim of this
      clinical study was to evaluate the effectiveness of a new method for ridge
      expansion with sagittal splitting using a new surgical device (Crest-Control Bone
      Splitting System, Meisinger) and to determine whether it is necessary to fill the
      expansion area with bone substitute to maintain the expanded bone volume.
      MATERIALS AND METHODS: During a 3-year period, a prospective study was performed
      in 32 patients (59% women, 41% men). All participants needed implants in the
      horizontally atrophied edentulous mandible and were treated in a private practice
      and a hospital. The only inclusion criteria were a mandibular ridge width between
      3 and 4 mm and ridge height of at least 11 mm. Expansion with horizontal
      splitting of the ridge was performed simultaneously with implant placement. In 17
      of the 32 arches, selected alternately, the expanded ridges were filled with a
      biphasic calcium phosphate (hydroxyapatite 60% and beta-tricalcium phosphate 40%)
      synthetic bone substitute (SBS 60/40). The other 15 expanded arches were left
      unfilled. All areas were covered with a resorbable collagen membrane (Bio-Gide,
      Geistlich). Results were analyzed with the Mann-Whitney and Kruskal-Wallis tests
      (alpha=.05). RESULTS: There was a significant difference (alpha=.02) between the
      patients who received SBS 60/40 (17 cases) and those who did not (15 cases). The
      ridges that received SBS 60/40 after expansion showed no bone resorption.
      CONCLUSION: Horizontal expansion of the ridge is easily reproducible. In this
      study, in very narrow ridges, a lack of bone substitute resulted in significant
      resorption of 3- to 4-mm-wide crests (5%), even after expansion. A bone
      substitute should be placed to maintain the alveolar bone walls after expansion.

PMID- 24451865
TI  - A randomized, blinded, controlled clinical study of particulate anorganic bovine
      bone mineral and calcium phosphosilicate putty bone substitutes for socket
      preservation.
AB  - PURPOSE: The purpose of this study was to compare the clinical efficacy of an
      anorganic bovine bone graft particulate to that of a calcium phosphosilicate
      putty alloplast for socket preservation. MATERIALS AND METHODS: Thirty teeth were
      extracted from 24 patients. The sockets were debrided and received anorganic
      bovine bone mineral (BOV, n=12), calcium phosphosilicate putty (PUT, n=12), or no
      graft (CTRL, n=6). The sockets were assessed clinically and radiographically 5
      months later. Eight sockets in the BOV group and nine in the PUT group received
      implants 5 to 6 months postgrafting. The maximum implant insertion torque (MIT)
      was measured as an index of primary implant stability. The data were analyzed
      with the Mann-Whitney test. RESULTS: Both test groups had statistically
      significantly less reduction in mean ridge width (BOV: 1.39+/-0.57 mm; PUT:
      1.26+/-0.41 mm) in comparison to the control group (2.53+/-0.59 mm). No
      statistically significant difference was identified between the test groups. MIT
      for PUT was <=35 N/cm2 (MIT grade 4) for seven of the nine implants. MIT values
      in the BOV group ranged from grade 1 (10 to 19 N/cm2) to grade 4, which was
      statistically significantly lower than for the PUT group. The overall implant
      success rate was 94.1% (16 of 17 implants were successful). No implants were lost
      in the PUT group; one implant failed in the BOV group. CONCLUSION: Both tested
      bone substitutes can be recommended for preservation of alveolar ridge width
      following extraction. PUT might be more suitable for achieving primary stability
      for implants placed at 5 to 6 months postextraction.

PMID- 24451866
TI  - Clinical and radiologic experience with moderately rough oxidized titanium
      implants: up to 10 years of retrospective follow-up.
AB  - PURPOSE: The long-term success of machined-surface implants is well documented,
      whereas the reliability of the moderately rough oxidized implant surface has not
      been definitively assessed in the long term. The aim of this retrospective study
      was to assess the long-term clinical and radiologic outcomes of moderately rough
      oxidized implants supporting fixed prostheses. MATERIALS AND METHODS: Seventy
      three consecutive patients needing an implant-supported restoration received 1 to
      11 implants each (n=167). All implants (82 cylindric and 85 tapered-body
      implants) had a self-tapping design and a moderately rough oxidized surface and
      were immediately loaded (n=48) or loaded after a delay (n=113). Patients were
      followed for up to 10 years. Outcomes were implant and prosthetic survival rates,
      peri-implant bone level changes, bleeding on probing, and plaque and gingival
      indices. RESULTS: One patient (one implant) dropped out. Seventy-two patients
      (166 implants) were followed for at least 8 years (mean, 8.82 years; range, 8.0
      to 10.4 years. No implants or prostheses were lost, resulting in a cumulative
      implant and prosthetic survival rate of 100% after up to 10 years in function. At
      the final follow-up, the accumulated mean marginal bone loss values were -1.72+/
      1.53 mm (n=27) and -1.27+/-1.67 mm (n=44) for cylindric and tapered implants,
      respectively, with no statistically significant difference. Bleeding on probing
      was 12.1%. The cumulative plaque score was 19.7%; 83.8% of patients showed normal
      gingiva, 10.1% displayed mild inflammation, and 6.1% showed moderate
      inflammation. CONCLUSION: This retrospective study of 73 patients treated with
      either cylindric or tapered-body moderately rough oxidized implants and followed
      for up to 10 years demonstrated good treatment outcomes with regard to implant
      survival, marginal bone changes, and soft tissue conditions.

PMID- 24451867
TI  - Effect of implant support for prostheses on electromyographic activity of
      masseter muscle and jaw movement in patients after mandibular fibula free flap
      reconstruction.
AB  - PURPOSE: Dental implants are used to stabilize, support, and retain prostheses in
      the mandible following fibula free flap reconstruction. A previous longitudinal
      prospective study showed that an implant-supported prosthesis (IP) provided
      additional improvement in masticatory performance compared to a conventional
      prosthesis (CP). Therefore, in this paper, the impact of implant retention and
      support of mandibular prostheses on neuromuscular function is reported via a
      within-subject analysis. MATERIALS AND METHODS: Forty-six participants were
      enrolled in the study. Prosthetic treatment with a CP was completed in 33
      subjects following oromandibular resection and fibula free flap reconstruction.
      Twenty-five subjects completed evaluation of the CP after an adaptation period.
      Standardized masticatory tests with peanuts were given to subjects on the defect
      and nondefect chewing sides. Electromyography (EMG) of masseter muscles and jaw
      movement was performed and recorded simultaneously in 19 of these subjects. IP
      treatment was then completed in 16 of these subjects, and 15 of them participated
      in the IP evaluation after an adaptation period. Of these 15 subjects, 13
      completed EMG and jaw movement recordings for both CP and IP. RESULTS: EMG
      activity of the defect-side masseter muscle increased significantly from CP to IP
      conditions when chewing on either side, but no significant change was found for
      nondefect-side muscle activity. Jaw movement parameters showed no significant
      changes from CP to IP. CONCLUSION: In patients restored with mandibular fibula
      free flap reconstruction, implant support for mandibular prostheses has the
      benefit of permitting greater muscle effort on the defect side, irrespective of
      the side on which the bolus is being chewed. The impact of an IP on jaw movements
      is limited.

PMID- 24451868
TI  - Incidence of implant buccal plate fenestration in the esthetic zone: a cone beam
      computed tomography study.
AB  - PURPOSE: The aim of this cone beam computed tomography (CBCT) study was to
      investigate the incidence of fenestration and associated risk factors with
      virtual placement of an implant in the maxillary incisor region. MATERIALS AND
      METHODS: Edentulous ridges missing a maxillary central or lateral incisor and
      amenable for single implant placement were included. Root-form implants (4*12 mm
      and 3.5*12 mm for the central and lateral incisors, respectively) were placed
      virtually in the edentulous space following the axis of the ipsilateral crown.
      Buccolingually, the implants were placed in the ideal prosthetic cingulum
      position. The angles of the ridge (RA) and implants (IA) in relation to the hard
      palate and the incidence of fenestration were recorded. RESULTS: A total of 48
      CBCT scans were analyzed. The mean RA and IA were 124.32 degrees and 110.91
      degrees, respectively. Nine cases resulted in fenestration, equivalent to 18.75%
      of the total cases. The discrepancy between the RA and IA was statistically
      significantly larger in the fenestration sites (19.93 degrees) than in the
      nonfenestration sites (13.05 degrees). The concavity depth of the alveolar ridge
      was statistically significantly higher in the fenestration sites (4.79 mm) than
      in the nonfenestration sites (3.40 mm). CONCLUSION: Within the limitations of
      this study, it can be concluded that the occurrence of fenestration is common
      (approximately 20%) if an implant is placed in the cingulum position with the
      axis following that of its restoration.

PMID- 24451869
TI  - Three-dimensional volume change of grafted bone in the maxillary sinus.
AB  - PURPOSE: The purpose of this study was to evaluate the three-dimensional
      radiographic changes of 100% anorganic bovine bone xenograft volume in a grafted
      maxillary sinus, based on a computerized analysis of cone-beam computed
      tomography (CBCT) scan. MATERIALS AND METHODS: A maxillary sinus augmentation
      procedure done with a lateral approach using 100% anorganic bovine bone was
      performed in 20 patients. A CBCT scan of the grafted area was taken immediately
      after the procedure (T1) and 8 to 9 months later (T2). CBCT scan data were
      analyzed with image processing software to evaluate differences in the volume of
      grafted material between T1 and T2. Residual ridge height and width were also
      measured at T1. RESULTS: The mean residual bone height and width at the implant
      sites was 4.40+/-0.87 mm and 7.9+/-2.22 mm, respectively. The mean graft volume
      was 1,432+/-539 mm3 and 1,287+/-498 mm3 at T1 and T2, respectively. A significant
      difference in graft volume was found between T1 and T2 data by paired t test
      (P=.01). The mean ratio between the volume at T2 and the volume at T1 was 0.90+/
      0.12, meaning a graft volume contraction of 10%. CONCLUSION: Within the limits of
      the present investigation, good stability of anorganic bovine bone graft volume
      up to 8 months after the grafting procedure was demonstrated. Three-dimensional
      computed tomographic volumetric assessment seems to be a promising approach to
      quantify long-term changes in the regenerated area.

PMID- 24451870
TI  - Vertical ridge augmentation with titanium-reinforced, dense-PTFE membranes and a
      combination of particulated autogenous bone and anorganic bovine bone-derived
      mineral: a prospective case series in 19 patients.
AB  - PURPOSE: This prospective case series evaluated the use of a new titanium
      reinforced nonresorbable membrane (high-density polytetrafluoroethylene), in
      combination with a mixture of anorganic bovine bone-derived mineral (ABBM) and
      autogenous particulated bone, for vertical augmentation of deficient alveolar
      ridges. MATERIALS AND METHODS: A mixture of ABBM and autogenous particulated bone
      was used for vertical ridge augmentation and covered with a new titanium
      reinforced nonresorbable membrane. Ridge measurements were obtained before and
      after the procedure, complications were recorded, and biopsy specimens were taken
      for histologic examination. RESULTS: Twenty vertical ridge augmentation
      procedures were carried out in 19 patients. All treated defect sites exhibited
      excellent bone formation, with an average bone gain of 5.45 mm (standard
      deviation 1.93 mm). The healing period was uneventful, and no complications were
      observed. Eight specimens were examined histologically; on average, autogenous or
      regenerated bone represented 36.6% of the specimens, ABBM 16.6%, and marrow space
      46.8%. No inflammatory responses or foreign-body reactions were noted in the
      specimens. CONCLUSION: The treatment of vertically deficient alveolar ridges with
      guided bone regeneration using a mixture of autogenous bone and ABBM and a new
      titanium-reinforced nonresorbable membrane can be considered successful.

PMID- 24451871
TI  - The effect of magnesium-incorporated hydroxyapatite coating on titanium implant
      fixation in ovariectomized rats.
AB  - PURPOSE: This study compared the effect of magnesium-incorporated hydroxyapatite
      (MgHA) coating with that of HA coating on implant fixation in ovariectomized
      (OVX) rats. MATERIALS AND METHODS: Coatings of HA and MgHA (10 mol% Ca2+ replaced
      by Mg2+) were prepared on the surface of titanium substrates using the sol-gel
      dip-coating method, and powders of HA and MgHA were produced by the same method.
      The two kinds of materials were then characterized by scanning electron
      microscopy and x-ray diffraction. Twelve weeks after bilateral ovariectomy, 18
      OVX rats received implants in the distal femora; half of the implants were HA
      coated and the other half were MgHA-coated. After 12 weeks of healing, rats were
      selected randomly for histomorphometry, microcomputed tomography evaluation, and
      biomechanical testing. RESULTS: Surface characterization analysis demonstrated
      that the addition of Mg did not dramatically change the surface topography or
      apatite patterns of the coating. Histomorphometry revealed higher bone-to-implant
      contact and bone area ratio for MgHA-coated implants than for HA-coated implants.
      Microcomputed tomographic evaluation revealed improved trabecular parameters and
      increased osseointegration for MgHA-coated implants. Biomechanical testing
      revealed that the MgHA coating increased the maximum push-out force and
      interfacial shear strength compared to the HA coating. CONCLUSION: Mg
      incorporated into an HA coating on titanium implants could improve the biologic
      fixation of implants in osteoporotic bone.

PMID- 24451872
TI  - A pilot histologic comparison of bone-to-implant contact between phosphate-coated
      and control titanium implants in the canine model.
AB  - PURPOSE: This study tested the null hypothesis that phosphate-treated titanium
      implants would perform no differently on mineral apposition rates (MARs), new
      bone-to-implant contact (new BIC), and total bone-to-implant contact (total BIC)
      compared to standard titanium implants. MATERIALS AND METHODS: Forty 3.3*8.0-mm
      titanium implants, either phosphate-treated or untreated, were placed in the
      mandibles of five foxhounds following 6 weeks of postextraction healing. The
      untreated implants (control) had sandblasted, acid-etched (SLA) surfaces, while
      the treated implants were electrolytically phosphorylated at 50 volts (T50) or
      100 volts (T100). Confocal and histologic analyses were performed on all the
      implants after 4 weeks of healing. RESULTS: The MARs could not be analyzed due to
      a lack of delineation between the three bone markers. New BIC results for control
      implants ranged from 6.0% to 56.0% with a mean of 23.92% and standard deviation
      (SD) of 13.29%; T50 implants ranged from 8.0% to 43.0% with a mean of 22.29% and
      SD of 10.26%; and T100 implants ranged from 0.0% to 47.0% with a mean of 17.43%
      and SD of 11.40%. Total BIC results for control implants ranged from 8.0% to
      68.0% BIC with a mean of 41.4% and SD of 19.3%; T50 implants ranged from 21.0% to
      65.0% with a mean of 43.7% and SD of 15.2%; and T100 implants ranged from 5.0% to
      68.0% with a mean of 38.0% and SD of 19.5%. CONCLUSION: Within the limitations of
      this pilot study, no significant differences in new BIC or total BIC were found
      between the three implant groups (C, T50, and T100). Given the very large sample
      size required to show clinically significant differences, phosphated surfaces do
      not appear to provide additional advantages to SLA surfaces.

PMID- 24451873
TI  - In vitro and in vivo evaluation of the osteogenic ability of implant surfaces
      with a local delivery of simvastatin.
AB  - PURPOSE: This study established local delivery with a calcium phosphate (CaP)
      coating and investigated effects of delivery on implant osseointegration by in
      vitro and in vivo experiments. MATERIAL AND METHODS: Simvastatin was prepared
      onto titanium surfaces with varying concentration (10-7, 10-6, 10-5, and 10-4
      mol/L). Surface characteristics were performed by field-emission scanning
      electron microscope (FSEM), x-ray diffractometer (XRD), and fourier transform
      infrared spectroscopy (FTIR). Alkaline phosphatase activity (ALP) and osteocalcin
      release were used to measure osteoblastic activities. Ovariectomized rats
      randomly received control and test implants in both tibiae. After 4 and 12 weeks
      of implantation, the tibiae were retrieved and prepared for histomorphometric
      evaluation. RESULTS: FSEM observation showed that the size of flakes decreased
      with an increase of simvastatin concentrations. XRD and FTIR examinations
      demonstrated that all coatings were composed of octacalcium phosphate (OCP).
      Simvastatin-loaded titanium surface had an increased effect on ALP activities at
      different concentrations on day 4 and day 7, and only the 10-6 mol/L group showed
      significant differences on day 14 (P<.05). The 10-6 mol/L group showed
      significant expression of osteocalcin (P<.05). Test implants (10-6 mol/L) showed
      a significantly greater bone area and bone-implant contact compared to control
      implants during the observation periods (P<.05). CONCLUSIONS: It was concluded
      that the local delivery of simvastatin was established onto implant surfaces
      using the biomimetic CaP coating and could improve osteoblast function and
      implant osseointegration in ovariectomized rats.

PMID- 24451874
TI  - Impact of caffeine and/or estrogen deficiency on trabecular bone area and
      healing: a study in rats.
AB  - PURPOSE: To evaluate the effects of caffeine and/or estrogen deficiency on
      trabecular bone area (TBA) and bone healing in rats. MATERIALS AND METHODS: Rats
      were divided into groups (n=15/group) as follows: control, caffeine, ovariectomy
      (OVX), and caffeine/OVX. Critical-sized defects were created in the tibiae (57
      days after beginning caffeine administration and 43 days after OVX). The intact
      femurs were evaluated for TBA and the number of positive cells for tartrate
      resistant acid phosphatase (TRAP), receptor activator of nuclear factor-kappaB
      ligand (RANKL), and osteoprotegerin (OPG). In the defects, bone healing, the
      number of TRAP+ and RANKL/OPG+ cells, and gene expression of bone morphogenetic
      protein (BMP)-2, BMP-7, osteopontin, and CBP/p300-interacting-transactivator-with
      ED-rich-tail-2 (CITED-2) were evaluated. RESULTS: Bone healing was poorer in
      defects of the caffeine group than in those of the control group. The femurs of
      the OVX and OVX/caffeine groups presented lower TBAs and higher RANKL/OPG+ cell
      ratios. The number of TRAP+ cells was higher in femurs of the caffeine group and
      in defects of the OVX group. The caffeine/OVX group presented the highest
      RANKL/OPG+ cell ratio in femurs and defects. The OVX group presented the highest
      expression of BMP-2, BMP-7, and CITED-2. CONCLUSION: Caffeine affected bone
      healing, while estrogen deficiency mainly affected TBA, but no significant
      deleterious synergic effects of both conditions were observed.

PMID- 24451875
TI  - Biomechanical effects of different fixed partial denture designs planned on
      bicortically anchored short, graft-supported long, or 45-degree-inclined long
      implants in the posterior maxilla: a three-dimensional finite element analysis.
AB  - PURPOSE: The purpose of this study was to analyze the functional stresses around
      implants and supporting tissues placed in different combinations in the grafted
      and nongrafted atrophic posterior maxilla and to consider the acceptability of
      various fixed partial denture treatment options. MATERIALS AND METHODS: A
      computer model of the atrophic posterior maxilla was created from the computed
      tomography images of an actual patient. Three different treatment scenarios were
      modeled with partial denture restorations, grafted and nongrafted maxillary
      sinuses, and various implant inclinations. Oblique forces were applied to
      simulate chewing movements. Stress analyses were performed with a three
      dimensional finite element analysis computer program, and the von Mises and
      minimum principal stresses on the implants and supporting tissues were compared.
      RESULTS: In all models, minimum principal (compressive) stress peak points were
      the highest within the crestal cortical bone (49.761 MPa), lower within sinus
      cortical (14.144 MPa) and trabecular bone (4.347 MPa), and lowest within grafted
      bone (0.049 MPa). The second molar implant in the third model (5*11-mm implant,
      inclined 45 degrees) showed the highest von Mises stresses (499.50 MPa), and the
      second molar implant in the first model (6*5-mm implant) showed the lowest
      (219.63 MPa) von Mises stresses. CONCLUSION: The stress absorption capacity of
      graft material is not sufficient and is much lower than that of other supporting
      tissues. For a fixed partial prosthesis, the use of short, wide implants with
      sinus floor bicortical fixation was found to be the most feasible approach for
      the atrophied posterior maxilla.

PMID- 24451876
TI  - Split-thickness flap with a semicircular punched-ridge pedicled periosteal flap
      for implant restoration in highly atrophic patients: a technical note.
AB  - Attached gingiva is a crucial aspect of healthy peri-implant tissue. Severely
      atrophied jaws have minimal quantities of attached gingiva. Any surgical
      procedure bears the potential risk of further loss of attached gingiva. The split
      thickness flap described here provides excellent access. Using a biopsy punch,
      the periosteum is easily cut in semicircular fashion on the labial surface of the
      bone so that it remains pedicled on the lingual or palatal ridge. The split
      thickness flap permits fixation of the gingival flap to the periosteum. The
      periosteal flap is closed with sutures to achieve soft tissue closure over the
      implants even in case of simultaneous vestibuloplasty. 

PMID- 24451877
TI  - Fabrication of printed titanium shells for containment of BMP-2 composite graft
      materials for alveolar bone reconstruction.
AB  - The engineering, design, manufacture, and rationale for use of printed titanium
      shells for alveolar bone reconstruction using BMP-2/ACS/allograft are described.
      This is proposed as a possible improvement to the current hand-configured mesh
      graft technique in common use today. 

PMID- 24451878
TI  - Sp1-dependent regulation of PPARalpha in bone metabolism.
AB  - PURPOSE: Successful repair and regeneration in bone tissue engineering vastly
      depends on proper interaction between the tissue-engineered construct and the
      recipient's immune system. In clinical application, adverse responses to
      bioartificial implants may result in chronic inflammation and loss of the
      implant. It is known that prolonged inflammation linked to NF-kappaB inflammatory
      pathways inhibits bone-forming activity of osteoblast cells. Contributing to
      orchestrate inflammatory processes, the ligand-activated transcription factor
      peroxisome proliferator-activated receptor alpha (PPARalpha) holds inhibitory
      effects on NF-kappaB and CEBbeta activity. Sp1, a widely expressed transcription
      factor, has been linked to PPAR pathways, cellular homeostasis, and
      responsiveness to environmental perturbation. Formerly not being characterized,
      the role of PPARalpha in inflammatory-mediated bone loss requires further
      investigation. The aim of the present study was to identify regulatory
      transcription factor binding sites (TFBS) on the PPAR alpha promoter and to
      assess the role of Sp1 and associated proteins in its regulation. MATERIALS AND
      METHODS: In a first set of experiments, polymerase chain reaction assessed the
      presence of PPARalpha gene expression in isolated murine bone tissue. Deletion
      mutagenesis was performed on the human PPARalpha (hPPARalpha) promoter gene, and
      the deletion constructs were transiently transfected to murine osteoblasts to
      identify important TFBS. PPARalpha promoter-driven reporter gene expression was
      monitored in response to overexpression and repression of Sp1 to analyze
      functional transcription factor recruitment to the PPARalpha promoter. RESULTS:
      This study could demonstrate that the full-length hPPARalpha promoter contains
      inhibiting promoter regions and that hPPARalpha basal expression can be
      significantly increased by deletion mutagensis. Sp1 TFBS proved functional in the
      regulation of PPARalpha promoter activity, and the first five Sp1 motifs on the
      PPARalpha promoter were sufficient to significantly increase PPARalpha
      expression. Additional transient co-transfection experiments could not detect any
      direct effect of NF-kappaB/IkappaB downstream pathway on the regulation of
      PPARalpha promoter activity. Taken together, we could demonstrate that Sp1 plays
      a key role in transcriptional regulation of PPARalpha promoter activity and gene
      expression. CONCLUSION: This study provides further insight on Sp1-dependent
      PPARalpha regulatory mechanisms and suggests that Sp1-regulated PPARalpha
      expression plays a key role in inflammatory mediated bone loss.

PMID- 24451879
TI  - Improved enzymatic treatment for accurate cell counting from extracellular matrix
      rich periodontal ligament cell sheets.
AB  - PURPOSE: The objective of this study was to establish a method for accurate cell
      counting from matrix-rich cell sheets in the clinical setting. MATERIALS AND
      METHODS: Human periodontal ligament (HPDL) cells were obtained from healthy
      donors to prepare PDL cell sheets. To obtain single cell suspensions, the cell
      sheets were treated with three different enzymatic formulations: collagenase
      alone, trypsin-ethylenediaminetetraacetic acid (EDTA) alone, and a combination of
      collagenase and trypsin-EDTA. After cell dispersion, cell numbers and cell
      survival rates were measured. To evaluate damage to the cell surfaces from the
      enzymes, the dispersed cells were analyzed by a flow cytometer with an anti
      alkaline phosphatase antibody. RESULTS: Treatment with collagenase alone or
      trypsin-EDTA alone dispersed few cells from HPDL cell sheets. In contrast,
      combined treatment with collagenase and trypsin-EDTA successfully produced a
      large amount of single cells from cell sheets. Flow cytometry analysis showed
      that single cells obtained by combined use of collagenase and trypsin-EDTA
      preserved alkaline phosphatase epitopes on the cell surfaces. CONCLUSIONS: Cell
      sheets rich with extracellular matrix were dispersed via combined treatment with
      collagenase and trypsin-EDTA without destroying the expression of cell surface
      markers. The results suggest that this method would be useful for determining the
      accurate cell number of cell sheets for cell therapies and should also be
      applicable for other kinds of matrix-rich cell sheets.

PMID- 24451880
TI  - Evaluation of a collagen scaffold for cell-based bone repair.
AB  - PURPOSE: To determine whether a collagen scaffold could provide an environment
      for mesenchymal stem cell (MSC)-related bone repair of critical-size bone defects
      in rat calvaria. MATERIALS AND METHODS: Craniotomy defects were created in 28
      adult Sprague-Dawley rats. Two additional rats were used as MSC donors by means
      of femoral bone marrow lavage and culture. The rats were randomly divided into
      four groups: (1) empty/no graft; (2) collagen scaffold (matrix)+saline; (3)
      matrix+MSCs; (4) matrix+bone morphogenetic protein. The animals were euthanized
      28 days after surgery. Microcomputed tomographic reconstructions were obtained to
      measure bone fill. The specimens were processed for histologic examination, and
      the total defect and bone fill areas were measured. RESULTS: Mean bone fill (+/-
      standard deviation) of 9.25%+/-10.82%, 19.07%+/-17.38%, 44.21%+/-3.93%, and
      66.06%+/-15.08%, respectively, was observed for the four groups; the differences
      were statistically significant. Bone repair was statistically significant for
      groups 3 and 4. No significant difference was seen for bone repair between groups
      1 and 2 or between groups 3 and 4. Bone formation differed significantly across
      the four groups. Statistically significant changes in radiodensity were observed
      between groups 1 and 3, groups 1 and 4, and groups 2 and 4. Significant
      differences were not observed between groups 1 and 2, groups 2 and 3, or groups 3
      and 4. CONCLUSION: After grafting of adult MSCs adherent within a collagen
      matrix, repair of bone was significant. Expanded three-dimensional collagen
      represents a radiolucent, resorbable, biocompatible scaffold that is capable of
      supporting MSC repair of bone.

PMID- 24451881
TI  - Paranasal bone: the prime factor affecting the decision to use transsinus vs
      zygomatic implants for biomechanical support for immediate function in maxillary
      dental implant reconstruction.
AB  - Paranasal bone affects the decision-making process for placement of implants for
      immediate function in the highly resorbed maxilla. The most important bone for
      apical fixation of implants in this setting is the lateral nasal bone mass.
      Maximum available bone mass found at the pyriform above the nasal fossa,
      designated M point, can most often engage two implants placed at 30-degree
      angles. The second most important area of paranasal bone mass is the subnasal
      bone of the premaxilla, which is required to engage an angled implant at the
      alveolar crest. However, only 4 to 5 mm in height is needed when implants are
      angled posterior to engage M point. The third most important paranasal bone site
      for implant fixation is the midline nasal crest extending upward to the vomer.
      This site, which is usually type 1/2 bone, can engage implants apically and
      provide enough fixation for immediate function even if implants are short. These
      anatomical bone sites enable placement of implants to obtain a 12- to 15-mm
      anterior-posterior spread, which is favorable for immediate function. 

PMID- 24451882
TI  - Implant placement in alveolar composite defects regenerated with rhBMP-2,
      anorganic bovine bone, and titanium mesh: a report of eight reconstructed sites.
AB  - PURPOSE: To present a retrospective report of eight significant alveolar defects
      in which the alveolus was regenerated with recombinant human bone morphogenetic
      protein 2 (rhBMP-2) combined with anorganic bovine bone and contoured using
      titanium mesh to facilitate implant-supported restorations. MATERIALS AND
      METHODS: A total of seven patients underwent extractions and debridement of the
      compromised alveolar sites with simultaneous grafting using a mixture of rhBMP-2
      and anorganic bovine bone. The three-dimensional contour of the compromised
      alveolus was reestablished using titanium mesh with rigid screw fixation.
      Implants were placed a minimum of 6 months after healing and subsequently were
      restored. RESULTS: The treated defects were successfully regenerated and did not
      require any additional surgery prior to implant placement or prosthetic
      restoration. A total of 14 implants were placed and restored with fixed single or
      multiple restorations. Thirteen of the 23 treated sites were in the anterior
      esthetic zone. CONCLUSION: Vertical and horizontal alveolar bone defects can be
      predictably regenerated by grafting with a combination of rhBMP-2 and anorganic
      bovine bone contained by titanium mesh to successfully accommodate implant
      placement.

PMID- 24451883
TI  - New-design dental implants: a 1-year prospective clinical study of 344
      consecutively placed implants comparing immediate loading versus delayed loading
      and flapless versus full-thickness flap.
AB  - PURPOSE: This study compared the 1-year success rates of immediately loaded
      dental implants to delayed loaded implants, regardless of the surgical technique
      (flapless or conventional full-thickness flap) and regardless of extraction time.
      It also examined whether the surgical technique had an influence on the success
      rate of the immediately loaded implants. MATERIALS AND METHODS: A total of 344
      dental implants, some with a new expanded winged-thread design, were placed in
      155 patients; 53% of the implants were immediately loaded. Of the immediately
      loaded implants, 68.9% were placed with a flapless surgical technique and 88%
      were placed in extraction sites. Pocket depth, mobility, bleeding on probing,
      presence of erythema, pain, or radiolucency around the implants, as well as
      clinical findings, were recorded. Implants were followed from placement through
      definitive restoration. Descriptive, univariate, and multivariate analyses using
      clustered marginal approach of the Cox proportional hazards model were applied.
      RESULTS: Of the 344 implants in the study, 10 (2.9%) failures were recorded, 7 of
      which were immediately loaded; however, there was no significant difference in
      failure rates between the immediate and delayed loading groups. Seven of the
      implants that failed were placed with a flapless (extraction site) technique;
      however, there was no significant difference in the failure rates between the
      flapless versus full-thickness flap technique in immediately loaded implants.
      CONCLUSIONS: The clinical success of immediately loaded implants after 1 year
      showed no difference from the success rate of delayed loaded implants. The
      implantation procedure (flapless versus conventional flap) or extraction time
      also had no influence on the success rate of the immediately loaded implants.

PMID- 24451884
TI  - Combined immediate loading of zygomatic and mandibular implants: a preliminary 2
      year report of 19 patients.
AB  - PURPOSE: A retrospective study was performed to evaluate the feasibility of
      simultaneous use of immediately loaded zygomatic and mandibular implants for full
      maxillomandibular restoration. MATERIALS AND METHODS: A total of 40 zygomatic and
      112 conventional implants were placed in 19 edentulous and partially edentulous
      patients and restored with full-arch acrylic resin prostheses within 3 hours of
      surgery. Implant insertion torque values were between 35 and 45 Ncm. RESULTS:
      During the 1-year follow-up period, none of the 19 patients experienced implant
      or prosthesis failures. The patients did not experience any sinus infections or
      any other surgical complications from the performed procedures. CONCLUSION:
      Zygomatic and conventional implants can be simultaneously placed in the maxilla
      and mandible and successfully loaded with an acrylic resin prosthesis using the
      All-on-Four concept.

PMID- 24451885
TI  - Angled dental implant placement into the vomer/nasal crest of atrophic maxillae
      for All-on-Four immediate function: a 2-year clinical study of 100 consecutive
      patients.
AB  - PURPOSE: To report on the use of angled implants placed into the vomer/nasal
      crest to support a complete-arch maxillary prosthesis. MATERIALS AND METHODS:
      Consecutive patients were treated with the All-on-Four concept to restore the
      maxillary dentition. When bone volume in the subnasal region was inadequate,
      angled implants were placed into the vomer/nasal crest area to support the
      restoration. All implants were loaded immediately. RESULTS: One hundred
      consecutive maxillary All-on-Four patients were treated over a period of 2 years.
      Four hundred six implants were placed; 12 were inserted into the vomer/nasal
      crest area. One year later, at definitive restoration, the 12 vomer implants were
      found to be osseointegrated without bone loss or instability. CONCLUSIONS:
      Midline maxillary bone volume at the nasal crest appeared to be a viable
      alternative to the lateral nasal rim when subnasal bone was deficient. Vomer
      implants allowed for immediate function or were sometimes used as a rescue
      implant when an anterior implant failed.

PMID- 24451886
TI  - The deception and fallacies of sponsored randomized prospective double-blinded
      clinical trials: the bisphosphonate research example.
AB  - The randomized prospective double-blinded clinical trial (RCT) is accepted as
      Level I evidence and is highly regarded. However, RCTs that gained FDA approval
      of drugs such as Vioxx, Fen-Phen, and oral and intravenous bisphosphonates have
      proven to generate misleading results and have not adequately identified serious
      adverse reactions. The development, research, and clinical marketing of the oral
      and intravenous bisphosphonates can serve as a representative example for the
      deteriorated value of many of today's RCTs. The expected high value of RCTs is
      jeopardized by: (1) sponsorship that incorporates bias; (2) randomization that
      can select out an expected improved result or eliminate higher-risk individuals;
      (3) experimental design that can avoid recognition of serious adverse reactions;
      (4) blinding that can easily become unblinded by the color, shape, odor, or
      administration requirements of a drug; (5) definitions that can define an
      observation as something other than what it actually represents, or fail to
      define it as an adverse reaction; (6) labeling of retrospective data as a
      prospective trial by using adjudicators prospectively to look at retrospective
      data; (7) change of the length of study to avoid the longer-term adverse reaction
      from accumulation of drug or treatment effects; (8) ghost writing, as when drug
      company physicians or a hired corporation either edit or write the entire
      protocol and/or manuscript for publication. Such corruption of the well-intended
      properly conducted RCT should be viewed with a sense of outrage by practitioners
      and requires a restructuring of the levels of evidence accepted today. 

PMID- 24451887
TI  - A review of pharmaceutical agents and oral bone health: how osteonecrosis of the
      jaw has affected the field.
AB  - Just a decade ago, the outlook appeared limitless for the use of bisphosphonates
      for the treatment of a large number of metabolic bone diseases ranging from
      osteoporosis to cancer-related bone alterations to oral bone loss. Soon
      thereafter, however, osteonecrosis of the jaw (ONJ) emerged as a rare but
      significant condition associated with bisphosphonate treatment. Although many
      questions remain concerning ONJ, some significant knowledge has been gained over
      the past decade. Ideas have emerged regarding how to stage and treat the
      condition, and a number of preclinical models have been developed that will soon
      begin to speed progress toward understanding the pathophysiology of this
      condition. Researchers have also discovered that ONJ is not specific to
      bisphosphonates, as other potent antiremodeling agents have now been associated
      with the condition. While antiremodeling agents remain essential tools in
      medicine, ONJ has somewhat slowed the momentum for this drug class, especially as
      it relates to new and emerging applications. Until more effective prevention or
      treatment regimens for ONJ are developed, this side effect of remodeling
      suppression will continue-for better or worse-to have a significant impact on the
      field. One potential treatment option may be in the form of osteoanabolics.
      Exciting new data have emerged demonstrating the efficacy of teriparatide
      (parathyroid hormone) in reversing oral cavity bone loss and even as a potential
      therapy for ONJ. 

PMID- 24451888
TI  - Commentary: cellular destruction vs cellular promotion.

PMID- 24451889
TI  - A novel approach for skin rejuvenation by regenerative medicine: delivery of stem
      cell-derived growth factors through an iontophoretic system.
AB  - PURPOSE: It was hypothesized that mesenchymal stem cell (MSC)-derived growth
      factor applied by iontophoretic transdermal delivery might improve ultraviolet
      beam (UVB)-induced photoaged skin. This experimental study was performed to
      confirm this hypothesis. MATERIALS AND METHODS: Photoaged skin was induced in
      nude rat after an 8-week regimen of UVB irradiation, and an MSC-conditioned
      medium (MSC-CM) was conducted by an iontophoretic transdermal transport system.
      The effect of iontophoresis with MSC-CM was evaluated by replica method and
      measurement of the hyaluronic acid level in the dermis after treatment. RESULTS:
      MSC-CM conducted by iontophoresis significantly reduced all parameters for
      wrinkles and increased hyaluronic acid in the dermis. CONCLUSION: MSC-CM
      application by iontophoresis can be considered as a supplemental treatment to the
      methods for skin rejuvenation.

PMID- 24451890
TI  - Island osteoperiosteal flap vitality when isolated from basal bone by silicone
      interposition: an experimental study in rabbit tibia.
AB  - PURPOSE: This study sought to confirm, through histologic evaluation, the
      vitality and viability of the island osteoperiosteal flap (i-flap) in a rabbit
      tibia model. MATERIALS AND METHODS: In four rabbits, an osteotomy was performed
      on the tibial aspect of the right leg. A bone flap was raised, but the periosteal
      attachment was kept intact. The free-floating i-flap was separated from the rest
      of the bone by a silicone sheet. The rabbits were to be sacrificed after 1, 2, 4,
      and 8 weeks and histologic samples examined. RESULTS: All surgeries were
      accomplished successfully; however, three animals showed fractured tibiae within
      a few days after surgery and were sacrificed immediately after the fractures were
      discovered. The fourth rabbit was sacrificed at 4 weeks. Histologic specimens
      showed vital new bone in the i-flap area and signs of remodeling in the
      transition zone and the original basal bone. CONCLUSION: The i-flap remained
      vital. This suggests potential for use in bone augmentation strategies,
      particularly for the alveolar split procedure.

PMID- 24451891
TI  - The effect of gabapentin-lactam hydroxamic acid derivatives on ovine osteoblast
      proliferation and phenotype: perspectives for tissue engineering application.
AB  - PURPOSE: Modern bone tissue engineering associated with mesenchymal stem cells
      (MSCs) provides promising treatment alternatives for the loss of bone, one of the
      foremost challenges in oral and craniofacial surgery today. The effect of
      gabapentin-lactam (GBP-L) and its analogs on osteogenic differentiated MSCs has
      not yet been deciphered. Consequently, this study investigates the effect of
      novel trans-8-tertbutylgabapentin-lactam (trans-8-TB-GBP-L) hydroxamic acid
      derivatives on metabolism, proliferation, and physiologic mineralization
      characteristics of ovine osteoblast cells. MATERIALS AND METHODS: Osteoblasts
      were extracted and prepared from sheep femoral heads and cultured in medium
      enriched with hydroxamic acid derivatives of trans-8-TB-GBP-L. The cell
      proliferation rate, cell metabolism, cell viability, and basic osteoblastic
      function were assessed. RESULTS: After 3 and 5 days of incubation, no significant
      increase in DNA content was detected in any of 12 test groups versus the control
      group. However, after 8 days of incubation, a significant increase of DNA
      contents in the test groups containing nanomolar concentrations of trans-8-TB-GBP
      L hydroxamic acid derivatives was found. No significant aberration in metabolic
      activity was detected when any of the test substances were applied. ALP displayed
      similar activity rates among the test groups and the control at all time points.
      Calcification of osteoblastic cells occurred solely when nanomolar concentrations
      were used. CONCLUSION: Trans-8-TB-GBP-L hydroxamic acid derivatives do not
      interfere with physiologic function and phenotype of ovine osteoblasts. However,
      when applied at nanomolar concentrations, the assessed GBP-L derivatives
      significantly increased the cell proliferation rate after 8 days of incubation,
      indicating a dose-response curve with the maximum peak at nanomolar concentration
      and a retarded drug response between 5 and 8 days.

PMID- 24451892
TI  - BMP-2/ACS/allograft for combined maxillary alveolar split/sinus floor grafting
      with and without simultaneous dental implant placement: report of 21 implants
      placed into 7 alveolar split sites followed for up to 3 years.
AB  - This report presents seven patients who were treated with combined alveolar
      split/sinus grafting technique and dental implants and followed for 1 to 3 years.
      The grafting material included bone morphogenetic protein-2 in an absorbable
      collagen sponge plus allograft. The procedure was successful in all patients, who
      received implants either simultaneously with grafting or 4 to 6 months after
      grafting. 

PMID- 24451893
TI  - Ultraviolet photofunctionalization of titanium implants.
AB  - In the face of growing demands and challenges in implant therapy, implant
      surfaces with improved biologic capabilities are required. This review paper
      summarizes the findings of recent in vitro and in vivo studies related to
      ultraviolet (UV) photofunctionalization of titanium. UV photofunctionalization is
      defined as an overall phenomenon of modification of titanium surfaces occuring
      after UV treatment, including the alteration of physicochemical properties and
      the enhancement of biologic capabilities. Bone morphogenesis around UV-treated
      titanium implants is distinctly improved compared with that seen around untreated
      control implants, leading to rapid and complete establishment of osseointegration
      with nearly 100% bone-to-implant contact in an animal model, as opposed to less
      than 55% for untreated implants. A series of in vitro studies demonstrated
      considerable enhancement of attachment, retention, and subsequent functional
      cascades of osteogenic cells derived from animals and humans after UV treatment.
      UV treatment converts titanium surfaces from hydrophobic to superhydrophilic and
      removes unavoidably contaminated hydrocarbons. UV-treated titanium surfaces also
      manifest a unique electrostatic status and act as direct cell attractants without
      the aid of ionic and organic bridges, which imparts a novel physicochemical
      functionality to titanium, which has long been understood as a bioinert material.
      UV treatment is simple and low in cost, and it has been proven effective for all
      types of titanium surfaces tested. These data suggest that UV
      photofunctionalization can be a novel, effective measure to improve implant
      therapy in the dental and orthopedic fields. Future research will focus on
      validating these findings in clinical studies. 

PMID- 24451894
TI  - Patients' responses to the communication of vascular risk in primary care: a
      qualitative study.
AB  - AIM: To examine the perspectives of patients identified as being at 'high risk'
      of cardiovascular events, with particular reference to the potential responses to
      risk messages. BACKGROUND: Systematic population screening for cardiovascular
      disease (CVD) aims to identify those at high risk and provide medication and
      lifestyle support. In the United Kingdom, this takes the form of the National
      Health Service Health Check. METHODS: We conducted a qualitative interview study.
      In 2011 we interviewed 37 patients, from seven UK primary care practices, who
      were at high risk of developing CVD. FINDINGS: Risk messages were delivered via
      face-to-face consultations or by letter and were relayed in either a
      'downplaying' or 'serious warning' style. Patients' accounts of receiving
      information about risk revealed two broad response styles: 'committed' (active
      resistance; commitment to change) and 'non-committed' (procrastination;
      downplaying and fatalism). Responses to risk messages are usually assumed to be
      due to individual characteristics but they may be explained by an interaction
      between the way risk is communicated and the patient's response style.

PMID- 24451895
TI  - Unmet Assistance Need Among Older American Indians: The Native Elder Care Study.
AB  - PURPOSE: We examined the prevalence and correlates of unmet assistance need with
      respect to activities of daily living (ADLs) and instrumental activities of daily
      living (IADLs) among older American Indians. DESIGN AND METHODS: Data for our
      analyses were collected in 2006-2008 as part of the Native Elder Care Study, a
      cross-sectional study of community-dwelling American Indians aged >=55 years. In
      person interviewer-administered surveys were used to collect data on demographic
      characteristics, physical functioning, mental and physical health, personal
      assistance needs, and psychosocial resources. RESULTS: Among those with an
      assistance need, 47.8% reported an unmet need with one or more ADLs or IADLs.
      Significant adjusted correlates of unmet assistance need included greater number
      of ADL and IADL difficulties and lower levels of social support. IMPLICATIONS:
      Initiatives and programs aimed at increasing social support and augmenting
      informal care networks can support efforts to meet American Indian adults'
      personal assistance needs.

PMID- 24451896
TI  - Implementing Culture Change in Nursing Homes: An Adaptive Leadership Framework.
AB  - PURPOSE OF THE STUDY: To describe key adaptive challenges and leadership
      behaviors to implement culture change for person-directed care. DESIGN AND
      METHODS: The study design was a qualitative, observational study of nursing home
      staff perceptions of the implementation of culture change in each of 3 nursing
      homes. We conducted 7 focus groups of licensed and unlicensed nursing staff,
      medical care providers, and administrators. Questions explored perceptions of
      facilitators and barriers to culture change. Using a template organizing style of
      analysis with immersion/crystallization, themes of barriers and facilitators were
      coded for adaptive challenges and leadership. RESULTS: Six key themes emerged,
      including relationships, standards and expectations, motivation and vision,
      workload, respect of personhood, and physical environment. Within each theme,
      participants identified barriers that were adaptive challenges and facilitators
      that were examples of adaptive leadership. Commonly identified challenges were
      how to provide person-directed care in the context of extant rules or policies or
      how to develop staff motivated to provide person-directed care. IMPLICATIONS:
      Implementing culture change requires the recognition of adaptive challenges for
      which there are no technical solutions, but which require reframing of norms and
      expectations, and the development of novel and flexible solutions. Managers and
      administrators seeking to implement person-directed care will need to consider
      the role of adaptive leadership to address these adaptive challenges.

PMID- 24451897
TI  - How Does Satisfaction With Medical Care Differ by Citizenship and Nativity
      Status?: A County-Level Multilevel Analysis.
AB  - PURPOSE OF THE STUDY: This study examined patient satisfaction among community
      dwelling older adults by their citizenship and nativity statuses. Since the
      welfare reform of 1996, citizenship has been an important factor in determining
      health care access among foreign-born individuals. Little is known regarding how
      the perceived satisfaction of older noncitizens compares with that of U.S.-born
      and naturalized citizens and how it is affected by county-level contextual
      characteristics. DESIGN AND METHODS: The 2000-2007 Medical Expenditure Panel
      Survey and linked Area Resource File were analyzed for 27,383 individuals (65+).
      Two dimensions of satisfaction (perceived access and ease of access) were
      examined using the Consumer Assessment of Health Plans Survey. Multilevel models
      were conducted using STATA. RESULTS: After both individual- and county-level
      covariates were controlled for, noncitizens were less likely to agree that their
      providers had spent enough time with them (p = .03) or had sufficiently explained
      treatment (p = .01) compared with U.S.-born citizens. Noncitizens' overall
      ratings of their providers were also lower (p < .001). Among those reported
      needs, noncitizens reported greater difficulties in accessing acute care (p <
      .001), routine care (p < .001), and specialty care (p = .009). In these models,
      some county-level characteristics (e.g., % of foreign-born individuals) were
      negatively associated with individual-level satisfaction. Interestingly,
      noncitizens from counties with high densities of foreign-born populations had
      higher overall satisfaction levels than did their U.S.-born counterparts (i.e.,
      interaction effect). IMPLICATIONS: Guided by the expanded Andersen model, this
      study demonstrates the importance of considering both individual- and county
      level contextual characteristics to accurately understand older noncitizens'
      access to health care and patient satisfaction.

PMID- 24451898
TI  - Location of the middle cranial fossa dural plate in patients with chronic otitis
      media.
AB  - AIM: This study aimed to determine whether or not the middle cranial fossa dural
      plate is located lower (i.e. more caudally) in patients with chronic otitis
      media, relative to adjacent structures. METHODS: The authors retrospectively
      investigated computed tomography temporal bone scans of 267 ears of 206 patients
      who had undergone surgery with a diagnosis of chronic otitis media, together with
      scans of 222 ears of 111 patients without chronic otitis media. The depth of the
      middle cranial fossa dural plates was recorded. RESULTS: The mean depth of the
      middle cranial fossa dural plate was 4.59 mm in the study group and 2.71 mm in
      the control group (p < 0.001). The middle cranial fossa dural plate was located
      lower in the right ear in both the study and control groups. CONCLUSION: The
      middle cranial fossa dural plate was located lower in patients with chronic
      otitis media, and in the right ears of both patients and controls. Surgeons
      should take this low location into consideration, and take extra care, during
      relevant surgery on patients with chronic otitis media.

PMID- 24451906
TI  - Hydrogen sulfide attenuates NMDA-induced neuronal injury via its anti-oxidative
      activity in the rat retina.
AB  - Although hydrogen sulfide (H2S) is generally thought to be a toxic gas, it has
      been reported to protect various tissues against ischemia-reperfusion injury. In
      the present study, we histologically investigated whether H2S, using sodium
      hydrosulfide (NaHS) as its donor, had a protective effect on N-methyl-d-aspartate
      (NMDA)-induced retinal injury in the rat in vivo. Under ketamine/xylazine
      anesthesia, male Sprague-Dawley rats were subjected to intravitreal NMDA
      injection. NaHS (0.163-120 MUmol/kg) was intraperitoneally administered 15 min
      before NMDA injection. Morphometric evaluation at 7 days after NMDA injection
      showed that intravitreal NMDA injection resulted in ganglion cell loss. NaHS dose
      dependently prevented this damage. NaHS (120 MUmol/kg) significantly decreased
      the numbers of TUNEL-positive, 4-hydroxy-2-nonenal-positive, and 8-OHdG-positive
      cells 12 h after NMDA injection. In another experimental series, we demonstrated
      that NaHS (120 MUmol/kg) significantly reduced the retinal injury induced by
      intravitreal NOC12 (400 nmol/eye), which was a nitric oxide donor and reported to
      induce oxidative stress, in the retina, 7 days after intravitreal injection.
      These results suggested that H2S protects retinal neurons against the injury
      induced by intravitreal NMDA in rats in vivo. Anti-oxidative activity of H2S are
      possibly involved in underlying protective mechanisms. 

PMID- 24451907
TI  - Childhood cancer camps: their role in adults surviving childhood cancers lives.
AB  - This study investigates the role that childhood cancer camps continue to play in
      the lives of adults surviving childhood cancers (ASCCs). Specifically, the
      purpose of this study is to understand the roles these camps play in enhancing
      ASCCs' psychosocial and emotional well-being and access to information. Twenty
      three ASCCs participated in this study. Illness narratives were used to
      understand ASCCs' camp experiences. Three themes emerged from the data analysis
      to reflect ASCCs' experiences: (1) normalcy, (2) meaningful camp experiences, and
      (3) access to information. Results show that in the years following camp
      participation, childhood cancer camps continue to play an important role in
      ASCCs' lives, providing them with ongoing social and emotional support and access
      to resources. 

PMID- 24451908
TI  - Eating behavior and BMI in adolescent survivors of brain tumor and acute
      lymphoblastic leukemia.
AB  - OBJECTIVES: Elevated body mass index (BMI) has been reported in pediatric cancer
      survivors. It is unclear whether this is related to altered energy intake (via
      disordered eating), decreased energy expenditure (via limited exercise), or
      treatment-related direct/indirect changes. The aims of this study are to describe
      the occurrence of overweight and obesity, exercise frequency, and the extent of
      disordered eating patterns in this sample of survivors, and to examine
      relationships among BMI, eating patterns, exercise frequency, and demographic and
      disease and treatment-related variables to identify those survivors most at risk
      for overweight/obesity. METHODS: This cross-sectional study recruited 98 cancer
      survivors (50 acute lymphoblastic leukemia [ALL], 48 brain tumor [BT]), aged 12
      to 17 years and >=12 months posttreatment from a large pediatric oncology
      hospital. Survivors completed health behavior measures assessing disordered
      eating patterns and physical activity. Clinical variables were obtained through
      medical record review. Univariate analyses were conducted to make comparisons on
      health behaviors by diagnosis, gender, treatment history, and BMI category.
      RESULTS: Fifty-two percent of ALL survivors and 41.7% of BT survivors were
      classified as overweight/obese. Overweight/obesity status was associated with
      higher cognitive restraint (odds ratio = 1.0; 95% confidence interval = 1.0-1.1).
      Only 12% of ALL survivors and 8.3% of BT survivors met Centers for Disease
      Control and Prevention guidelines for physical activity. Males reported more
      physical activity, t(96) = 2.2, P < .05. CONCLUSIONS: Overweight/obese survivors
      may attempt to purposefully restrict their food intake and rely less on
      physiological cues to regulate consumption. Survivors should be screened at
      follow-up for weight-related concerns.

PMID- 24451909
TI  - Why mothers accompany adolescent and young adult childhood cancer survivors to
      follow-up clinic visits.
AB  - PURPOSE: Parents often accompany adolescent and young adult (AYA) pediatric
      cancer survivors to follow-up oncology clinic visits and remain involved in their
      care, although little is known about their reasons for doing so. METHOD: This
      mixed methods (qualitative-quantitative) study of 76 mothers of AYA survivors of
      childhood cancer uses content analysis and logistic regression to identify and
      explore reasons mothers provided for coming to the visit. Demographic and
      treatment data are examined as potentially explanatory factors. RESULTS: Ten
      reasons (in decreasing order of frequency) were derived: Concern for Child's
      Health and Well-Being, Practical Support, Transportation, Familial Experience,
      General Support, Companionship, Personal Interest in Follow-up Care,
      Characteristics of their Child, Emotional Support, and Parental Duty. The reasons
      were not related to demographic or treatment factors. CONCLUSION: Mothers
      accompany AYAs to survivorship clinic for both maternal/family-focused and
      survivor-focused reasons that can be incorporated in survivorship and transition
      care to reflect ongoing communications among survivors, parents, and health care
      teams.

PMID- 24451910
TI  - The relationships between environmental bacterial exposure, airway bacterial
      colonization, and asthma.
AB  - PURPOSE OF REVIEW: Recent application of advanced culture-independent molecular
      techniques for the identification of microorganisms has contributed to our
      knowledge on the role of early-life microbial exposure and colonization in health
      and disease. The purpose of this review is to present the current perspectives
      regarding the role of microbial exposure and airway bacterial colonization on the
      development and the activity of asthma. RECENT FINDINGS: Recent findings continue
      to support the protective role of early-life diverse microbial exposure against
      the development of atopic diseases. However, airway bacterial colonization early
      in life serves as a risk factor for the development of asthma. Culture
      independent molecular techniques for the identification of microorganisms have
      challenged the traditional paradigm that the lower airway is a sterile
      compartment. Asthmatics, compared with nonasthmatics, appear to have a different
      lung microbiome composition and some of these differences might contribute to
      asthma activity, severity, and corticosteroid response. SUMMARY: Bacterial
      presence in the airway appears to influence the inception and may affect the
      activity of asthma. Complex interactions between different types and routes of
      bacterial exposures, the airway, and the immune system early in life may
      determine whether these exposures augment or reduce the risk of asthma
      development.

PMID- 24451911
TI  - Early weight gain and the development of asthma and atopy in children.
AB  - PURPOSE OF REVIEW: To provide perspective to the most recent evidence regarding
      the association between early weight gain in infancy and the development of
      asthma and atopy during childhood, and highlight the potential mechanisms
      involved. RECENT FINDINGS: Recently, several birth cohort studies involving more
      than 25 000 children have found a consistent association between early weight
      gain in the first 2 years of life and incident asthma during school age.
      Methodology differs substantially between the studies and complicates the
      establishment of definite conclusions. Specific mechanisms for this association
      have been proposed, including impairment in lung development and elevated levels
      of growth factors and cytokines associated with airway inflammation and
      remodeling. A limited number of studies indicate that early weight gain in
      infancy is also associated with recurrent wheezing during preschool age but not
      with the development of atopy. SUMMARY: A consistent association between early
      weight gain in infancy and incident asthma during school age has been observed in
      several cohort studies. The identification of this modifiable risk factor for the
      development of asthma opens the possibility of preventive intervention.
      Additional studies are necessary to clarify the involved mechanisms and some
      pending questions, such as the influence of early weight gain in asthma
      phenotypes and severity.

PMID- 24451912
TI  - Occupational allergy: respiratory hazards in healthcare workers.
AB  - PURPOSE OF REVIEW: Allergens are one group of respiratory hazards in the
      workplace of healthcare workers (HCWs). The purpose of this review is to
      summarize the recent advances in occupational allergy as well as potential
      hazardous agents in HCWs. RECENT FINDINGS: The review covers new developments on
      the epidemiology, diagnosis and management of occupational allergy in HCWs. This
      article also provides updated information on the prevalence of work-related
      respiratory symptoms, as well as on respiratory hazards among healthcare
      providers. SUMMARY: It is established that HCWs are at risk of asthma symptoms.
      The growing use of cleaning products is one of the causes of occupational airway
      disease in that group. Among healthcare professionals, the prevalence of asthma
      varies depending on worksite. Recent findings indicate a need for education among
      HCWs concerning occupational risks. A lack of knowledge of product components as
      well as about exposure to cleaning/disinfecting agents has been demonstrated.
      Further studies are necessary to determine the relative role of individual agents
      versus complex workplace exposures in the development of work-related asthma in
      HCWs.

PMID- 24451913
TI  - Airway effects of traffic-related air pollution on outdoor workers.
AB  - PURPOSE OF REVIEW: Traffic-related air pollution has been well documented to be
      associated with increased risks of airway diseases in the general population.
      Particularly, susceptible subgroups have included children and endurance athletes
      exercising outdoors. Relatively little has been published on the risks for
      outdoor workers. The purpose of this review is to identify the relative airway
      risks of outdoor work in areas with increased vehicular air pollution. RECENT
      FINDINGS: We found a small body of recent literature published on this topic.
      Most of the relevant studies have focused on traffic police, petrol pump workers,
      and highway workers, especially in the urban areas of high traffic pollution.
      These studies suggest increases in respiratory symptoms and reduction in
      spirometric indices in nonsmoking workers in these occupations when compared with
      control individuals. Research is needed to investigate the relationship with
      duration of exposures in these workers, and to determine the duration and
      reversibility of effects in order to develop standards for safe working
      exposures. SUMMARY: A significant impact on airway function and respiratory
      symptoms has been reported from outdoor work with exposure to traffic pollution.
      Further research is needed to confirm these associations and to develop standards
      for safe outdoor work in urban settings.

PMID- 24451914
TI  - Transient receptor potential channels and occupational exposure.
AB  - PURPOSE OF REVIEW: The discovery that a number of transient receptor potential
      (TRP) channels are expressed in a subpopulation of primary sensory neurons
      innervating the upper and lower airways as well as in nonneuronal cells in the
      airways and lungs has initiated a quest for the understanding of their role in
      the physiology and pathophysiology of the respiratory tract. RECENT FINDINGS:
      Various members of the TRP vanilloid subfamily (TRPV1, TRPV4) and the TRP ankyrin
      1 (TRPA1), because of their localization in peptidergic sensory neurons, promote
      airway neurogenic inflammation. In particular, TRPA1, which is gated by oxidative
      and nitrative stress byproducts, has been found to mediate inflammatory responses
      produced by an unprecedented series of toxic and irritant agents produced by air
      pollution, contained in cigarette smoke, and produced by accidental events at the
      workplace. The observation that reactive molecules endogenously produced in the
      airways/lungs of asthma, work-related asthma, and chronic obstructive pulmonary
      disease target TRPA1 underscores the primary role of the TRPA1 channel in these
      conditions. SUMMARY: Identification of TRP channels, and especially TRPA1, as
      major targets of oxidative/nitrative stress and a variety of irritant
      environmental agents supports the hypothesis that neurogenic inflammation plays
      an important role in work-related inflammatory diseases and that antagonists for
      such channels may be novel therapeutic options for the treatment of these
      diseases.

PMID- 24451915
TI  - Response to a letter regarding a paper entitled, "post-intervention TCD
      examination may be useful to predict outcome in acute ischemic stroke patients
      with successful intra-arterial intervention".

PMID- 24451917
TI  - Intrinsic Ge nanowire nonvolatile memory based on a simple core-shell structure.
AB  - Intrinsic Ge nanowires (NWs) with a Ge core covered by a thick Ge oxide shell are
      utilized to achieve nanoscale field-effect transistor nonvolatile memories, which
      show a large memory window and a high ON/OFF ratio with good retention. The
      retainable surface charge trapping is considered to be responsible for the memory
      effect, and the Ge oxide shell plays a key role as the insulating tunneling
      dielectric which must be thick enough to prevent stored surface charges from
      leaking out. Annealing the device in air is demonstrated to be a simple and
      effective way to attain thick Ge oxide on the Ge NW surface, and the Ge-NW-based
      memory corresponding to thick Ge oxide exhibits a much better retention
      capability compared with the case of thin Ge oxide. 

PMID- 24451916
TI  - Ultrahigh-gain photodetectors based on atomically thin graphene-MoS2
      heterostructures.
AB  - Due to its high carrier mobility, broadband absorption, and fast response time,
      the semi-metallic graphene is attractive for optoelectronics. Another two
      dimensional semiconducting material molybdenum disulfide (MoS2) is also known as
      light- sensitive. Here we show that a large-area and continuous MoS2 monolayer is
      achievable using a CVD method and graphene is transferable onto MoS2. We
      demonstrate that a photodetector based on the graphene/MoS2 heterostructure is
      able to provide a high photogain greater than 10(8). Our experiments show that
      the electron-hole pairs are produced in the MoS2 layer after light absorption and
      subsequently separated across the layers. Contradictory to the expectation based
      on the conventional built-in electric field model for metal-semiconductor
      contacts, photoelectrons are injected into the graphene layer rather than trapped
      in MoS2 due to the presence of a perpendicular effective electric field caused by
      the combination of the built-in electric field, the applied electrostatic field,
      and charged impurities or adsorbates, resulting in a tuneable photoresponsivity. 

PMID- 24451918
TI  - Ethylene glycol adjusted nanorod hematite film for active photoelectrochemical
      water splitting.
AB  - We reported a facile adjusted method for the synthesis of high surface area
      nanorod hematite film as a photoanode for application in water splitting.
      Crystalline hematite nanorods (EG-alpha-Fe2O3) are fabricated by
      electrodeposition in Fe(2+) precursor solution with the addition of ethylene
      glycol (EG) and followed by annealing at 450  degrees C. The nanorod hematite
      film fabricated by the modified electrodeposition approach exhibits a more
      uncompact structure than alpha-Fe2O3 obtained by directly electrodepositing on
      the FTO substrate. The optical and structural characteristics of the obtained
      film are also tested. The results infer that EG can tune the morphology of
      hematite and improve the photoabsorption in the visible light region due to its
      inducement of one-dimensional growth of crystal hematite. It also enhances the
      photoresponse activity of hematite in water splitting by improving the activities
      at the semiconductor/solution interface. The photocurrent density of EG-alpha
      Fe2O3 nanorods increased to 0.24 mA cm(-2) at 1.4 V vs. RHE in 1 M KOH (pH =
      13.6), almost 5 times higher than the original alpha-Fe2O3 (0.05 mA cm(-2),
      measured under the same conditions). 

PMID- 24451920
TI  - Replication of flexible polymer membranes with geometry-controllable nano
      apertures via a hierarchical mould-based dewetting.
AB  - Membranes with nano-apertures are versatile templates that possess a wide range
      of electronic, optical and biomedical applications. However, such membranes have
      been limited to silicon-based inorganic materials to utilize standard
      semiconductor processes. Here we report a new type of flexible and free-standing
      polymeric membrane with nano-apertures by exploiting high-wettability difference
      and geometrical reinforcement via multiscale, multilevel architecture. In the
      method, polymeric membranes with various pore sizes (50-800 nm) and shapes (dots,
      lines) are fabricated by a hierarchical mould-based dewetting of ultraviolet
      curable resins. In particular, the nano-pores are monolithically integrated on a
      two-level hierarchical supporting layer, allowing for the rapid (<5 min) and
      robust formation of multiscale and multilevel nano-apertures over large areas (2
      * 2 cm(2)).

PMID- 24451921
TI  - Guess who's not coming to dinner? Evaluating online restaurant reservations for
      disease surveillance.
AB  - BACKGROUND: Alternative data sources are used increasingly to augment traditional
      public health surveillance systems. Examples include over-the-counter medication
      sales and school absenteeism. OBJECTIVE: We sought to determine if an increase in
      restaurant table availabilities was associated with an increase in disease
      incidence, specifically influenza-like illness (ILI). METHODS: Restaurant table
      availability was monitored using OpenTable, an online restaurant table
      reservation site. A daily search was performed for restaurants with available
      tables for 2 at the hour and at half past the hour for 22 distinct times: between
      11:00 am-3:30 pm for lunch and between 6:00-11:30 PM for dinner. In the United
      States, we examined table availability for restaurants in Boston, Atlanta,
      Baltimore, and Miami. For Mexico, we studied table availabilities in Cancun,
      Mexico City, Puebla, Monterrey, and Guadalajara. Time series of restaurant use
      was compared with Google Flu Trends and ILI at the state and national levels for
      the United States and Mexico using the cross-correlation function. RESULTS:
      Differences in restaurant use were observed across sampling times and regions. We
      also noted similarities in time series trends between data on influenza activity
      and restaurant use. In some settings, significant correlations greater than 70%
      were noted between data on restaurant use and ILI trends. CONCLUSIONS: This study
      introduces and demonstrates the potential value of restaurant use data for event
      surveillance.

PMID- 24451919
TI  - Inverse Effect of Fluoxetine on Medial Prefrontal Cortex Activation During Reward
      Reversal in ADHD and Autism.
AB  - Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder
      (ASD) share brain function abnormalities during cognitive flexibility. Serotonin
      is involved in both disorders, and selective serotonin reuptake inhibitors
      (SSRIs) can modulate cognitive flexibility and improve behavior in both
      disorders. Thus, this study investigates shared and disorder-specific brain
      dysfunctions in these 2 disorders during reward reversal, and the acute effects
      of an SSRI on these. Age-matched boys with ADHD (15), ASD (18), and controls (21)
      were compared with functional magnetic resonance imaging (fMRI) during a reversal
      task. Patients were scanned twice, under either an acute dose of Fluoxetine or
      placebo in a double-blind, placebo-controlled randomized design. Repeated
      measures analyses within patients assessed drug effects. Patients under each drug
      condition were compared with controls to assess normalization effects. fMRI data
      showed that, under placebo, ASD boys underactivated medial prefrontal cortex
      (mPFC), compared with control and ADHD boys. Both patient groups shared decreased
      precuneus activation. Under Fluoxetine, mPFC activation was up-regulated and
      normalized in ASD boys relative to controls, but down-regulated in ADHD boys
      relative to placebo, which was concomitant with worse task performance in ADHD.
      Fluoxetine therefore has inverse effects on mPFC activation in ASD and ADHD
      during reversal learning, suggesting dissociated underlying serotonin
      abnormalities. 

PMID- 24451922
TI  - Decreased macular thickness in nonproliferative macular telangiectasia type 2
      with oral carbonic anhydrase inhibitors.
AB  - PURPOSE: To evaluate whether carbonic anhydrase inhibitors reduce the macular
      thickness and/or cystic spaces in patients with macular telangiectasia (MacTel)
      Type 2. METHODS: Retrospective review of patients with nonproliferative cystoid
      changes associated with MacTel seen at the University of Iowa between 2009 and
      2012. Carbonic anhydrase inhibitors were used in 8 patients with MacTel Type 2.
      Five patients with MacTel Type 2 were observed during this period. Initial and
      final visual acuities were documented. The presence of cystic spaces and the
      retinal thickness were measured with spectral-domain optical coherence
      tomography. RESULTS: Patients treated with oral carbonic anhydrase inhibitors
      showed significant reduction in both the cystoid cavities and central macular
      thickness when compared with the patients who were observed (-12.2 MUm; P =
      0.020). The reduction in retinal thickness was more pronounced in patients
      receiving acetazolamide (-20.13 MUm; P = 0.007) compared with methazolamide (
      6.25 MUm; P = 0.177). There was no significant change in visual acuity in
      patients receiving carbonic anhydrase inhibitors. Five patients with MacTel Type
      2 did not receive treatment and demonstrated no change in visual acuity, cystoid
      cavities, or central macular thickness. CONCLUSION: Oral carbonic anhydrase
      inhibitors, particularly acetazolamide, may decrease macular cystic cavities and
      reduce central macular thickness but does not appear to improve visual acuity.
      These findings have yet to be confirmed with a prospective treatment trial.

PMID- 24451923
TI  - Exacerbation of choroidal and retinal pigment epithelial atrophy after anti
      vascular endothelial growth factor treatment in neovascular age-related macular
      degeneration.
AB  - PURPOSE: To study the progression of retinal pigment epithelium (RPE) and
      choroidal atrophy in patients with neovascular age-related macular degeneration
      (AMD) and to assess for a possible association with the number and type of anti
      vascular endothelial growth factor treatments. METHODS: Patients with neovascular
      AMD and a minimum of 1-year follow-up were reviewed. Fellow eyes with
      nonneovascular AMD were used as control eyes. Retinal pigment epithelial atrophy
      area and choroidal thickness were determined using spectral-domain optical
      coherence tomography. Multivariable regression models were used for statistical
      analyses. RESULTS: A total of 415 eyes were included in the study, with a mean
      follow-up of 2.2 years. Eyes with neovascular AMD had greater progression of RPE
      atrophy and choroidal atrophy compared with those with nonneovascular AMD (P <
      0.001). Progression of RPE atrophy and choroidal atrophy was independently
      associated with the total number of injections of bevacizumab and ranibizumab
      (all P values <= 0.001). In the subgroup of 84 eyes with neovascular AMD and
      without RPE atrophy at baseline, only bevacizumab was associated with the
      progression of RPE atrophy (P = 0.003). This study likely lacked statistical
      power to detect an association with ranibizumab in this subgroup. CONCLUSION:
      Retinal pigment epithelial atrophy and choroidal atrophy in neovascular AMD seem
      to be exacerbated by anti-vascular endothelial growth factor treatment. Possible
      differences between bevacizumab and ranibizumab require further investigation.

PMID- 24451924
TI  - Spectral-domain optical coherence tomography study of macular structure as
      prognostic and determining factor for macular hole surgery outcome.

PMID- 24451925
TI  - Volume and composition of reflux after intravitreal injection.
AB  - PURPOSE: To quantify the amount of drug loss from cadaveric human eyes, which are
      injected via the pars plana with a known volume of dye at variable intraocular
      pressures. METHODS: Eight cadaver eyes were divided into 2 intraocular pressure
      groups: normal (15 mmHg; 4 eyes) or high (30 mmHg; 4 eyes). Each eye was injected
      with 50 MUL of hematoxylin dye, and the subsequent reflux was immediately
      collected on a Schirmer's test strip. The test strip was scanned and digitally
      analyzed to determine the area of saturation and total color intensity present.
      Using a previously established equation, total volume of reflux and the amount of
      dye within that reflux were calculated. RESULTS: The average total volume of
      refluxed fluid was 1.68 MUL (median, 0.62 MUL), with a range of 0 MUL to 8.05
      MUL. The average volume of refluxed dye was 0.37 MUL (median, 0.08 MUL), with a
      range of 0 MUL to 2.15 MUL. On average, only 0.74% of the original 50 MUL of
      injected dye was lost (median, 0.15%), with a range from 0% to 4.30%. CONCLUSION:
      Although the presence of subconjunctival bleb formation after intravitreal
      injection may be a concern to the clinician, data from the present study shows
      that only a very small amount of the injected therapeutic agent is lost in the
      reflux.

PMID- 24451926
TI  - Reply: To PMID 23584694.

PMID- 24451927
TI  - A genetic method for sex identification of raccoons (Procyon lotor) with using
      the ZFX and ZFY genes.
AB  - A genetic method for sex determination in raccoons was developed based on
      nucleotide differences of the zinc finger protein genes ZFX and ZFY. Four novel
      internal primers specific for ZFX or ZFY were designed. PCR amplification using
      two primer sets followed by agarose gel electrophoresis enabled sex
      determination. 141-bp and 447-bp bands were in both sex, and 346-bp band was
      specific only in male with primer set I. 345-bp and 447-bp bands were in both
      sex, and 141-bp band was specific only in male with primer set II, which could
      distinguish raccoon's electrophoresis pattern from three native carnivores in
      Hokkaido. This method will be useful for conservation genetics studies or
      biological analyses of raccoons. 

PMID- 24451928
TI  - Immune-stimulatory effects of a bacteria-based probiotic on peripheral leukocyte
      subpopulations and cytokine mRNA expression levels in scouring holstein calves.
AB  - Subpopulations of peripheral leukocytes and cytokine mRNA expression levels were
      evaluated in scouring and healthy Holstein calves (age 10 +/- 5 days; n=42)
      treated with a probiotic consisting of Lactobacillus plantarum, Enterococcus
      faecium and Clostridium butyricum. The calves were assigned to the scouring or
      healthy group and then subdivided into pathogen-positive treated (n=8), pathogen
      positive control (n=8), pathogen-negative treated (n=6), pathogen-negative
      control (n=6), healthy treated (n=6) and healthy control (n=8) groups. A single
      dose of the probiotic (3.0 g/100 kg body weight) was given to each calf in the
      treatment groups for 5 days. Blood samples were collected on the first day of
      scour occurrence (day 0) and on day 7. In the scouring calves, smaller peripheral
      leukocyte subpopulations and cytokine mRNA expression levels were noted on day 0.
      The numbers of CD3(+) T cells; CD4(+), CD8(+) and WC1(+) gammadelta T cell
      subsets; and CD14(+), CD21(+) and CD282(+) (TLR2) cells were significantly
      increased in the scouring and healthy treated calves on day 7. Furthermore,
      interleukin-6, tumor necrosis factor-alpha and interferon-gamma mRNA expression
      was elevated in the peripheral leukocytes of the scouring and healthy treated
      calves on day 7. The scouring calves given the probiotic recovered on day 7. A
      significantly smaller number of peripheral leukocytes and lower cytokine mRNA
      expression level might be induced by scouring in calves. Repeated probiotic
      administration might stimulate cellular immunity and encourage recovery from
      scouring in pre-weaning Holstein calves. 

PMID- 24451929
TI  - Species identification key of Korean mammal hair.
AB  - The hair microstructures of Korean terrestrial mammals from 23 species (22 wild
      and one domestic) were analyzed using light and scanning electron microscopy
      (SEM) to construct a hair identification key. The hairs were examined using the
      medulla structures and cuticular scales of guard hairs from the dorsal regions of
      mature adult animals. All cuticular scale structures in the hair of Rodentia,
      Lagomorpha, Carnivora and Insectivora showed the petal pattern, and those of
      Artiodactyla and Chiroptera showed the wave pattern and coronal pattern,
      respectively. Rodentia, Lagomorpha and Carnivora showed multicellular, and
      Insectivora and Artiodactyla showed unicellular regular, mesh or columnar in the
      medulla structures, respectively. Chiroptera did not show the medulla structures
      in their hair. We found that it is possible to distinguish between species and
      order based on general appearance, medulla structures and cuticular scales. Thus,
      we constructed a hair identification key with morphological characteristics from
      each species. This study suggests that hair identification keys could be useful
      in fields, such as forensic science, food safety and foraging ecology. 

PMID- 24451938
TI  - Promoting physical activity among older people in primary care using peer
      mentors.
AB  - INTRODUCTION: The home-based Otago Exercise Programme has been shown to increase
      sustained physical-activity levels in older people recruited through primary
      care, when supported by health professionals. The ProAct65+ trial is testing this
      programme using volunteer peer mentors to support behaviour change. This
      qualitative study explored how these peer mentors experienced their role.
      METHODS: Ten peer mentors from the ProAct65+ trial were interviewed. Semi
      structured interviews were audio-recorded, transcribed verbatim and thematically
      analysed. RESULTS: Peer mentors reported positive experiences including meeting
      new people, watching mentees progress, developing friendships and being shown
      gratitude for their support. Key barriers and facilitators to the mentoring
      process included the home and telephone as settings for support, geography and
      making contact with mentees. CONCLUSION: Findings from this study can help the
      development of peer mentor programmes in primary care for older people. Future
      programmes should recruit peer mentors who are local to where mentoring is needed
      to reduce travel difficulties.

PMID- 24451940
TI  - Multielements of medical caring in gastric cancer.

PMID- 24451939
TI  - Trianthema portulacastrum Linn. exerts chemoprevention of 7,12
      dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats.
AB  - Due to limited treatment options for advanced-stage metastatic breast cancer, a
      high priority should be given to develop non-toxic chemopreventive drugs. The
      value of various natural and dietary agents to reduce the risk of developing
      breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a
      dietary and medicinal plant, has been found to exert antihepatotoxic and
      antihepatocarcinogenic properties in rodents. This study was initiated to
      investigate mechanism-based chemopreventive potential of an ethanolic extract of
      T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated
      rat mammary gland carcinogenesis, an experimental tumor model that closely
      resembles human breast cancer. Rats had access to a basal diet supplemented with
      TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body
      weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated
      by oral administration of DMBA (50 mg/kg body weight). At the end of the study
      (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA
      induced mammary tumor incidence, total tumor burden and average tumor weight and
      reversed intratumor histopathological alterations. TPE dose-dependently
      suppressed proliferating cell nuclear antigen and cyclin D1 expression, induced
      apoptosis, upregulated proapoptotic protein Bax, downregulated antiapoptotic
      protein Bcl-2 and diminished the expression of nuclear and cytosolic beta-catenin
      in mammary tumors. Our results clearly provide the first experimental evidence
      that TPE exerts chemopreventive effect in the classical DMBA model of breast
      cancer by suppressing abnormal cell proliferation and inducing apoptosis mediated
      through alteration of Bax/Bcl-2 ratio. Mechanistically, TPE is capable of
      diminishing activated canonical Wnt/beta-catenin signaling to exhibit
      antiproliferative, proapoptotic and oncostatic effects during an early-stage
      breast cancer. These results may encourage further studies to explore full
      potential of T. portulacastrum phytoconstituents as breast cancer chemopreventive
      agents.

PMID- 24451941
TI  - A matched cohort study of laparoscopy-assisted and open total gastrectomy for
      advanced proximal gastric cancer without serosa invasion.
AB  - BACKGROUND: Little is known about the feasibility and safety of laparoscopy
      assisted total gastrectomy (LATG) with extended lymphadenectomy in patients with
      advanced gastric cancer (AGC). This study compared the technical feasibility,
      safety, and oncologic efficacy of LATG with open total gastrectomy (OTG) for AGC
      without serosa invasion. METHODS: From January 2009 to December 2011, 235
      patients underwent LATG and 153 patients underwent OTG for AGC without serosa
      invasion. Age, gender, and depth of invasion (pT2 and pT3) were matched by
      propensity scoring, and 116 patients (58 LATG and 58 OTG) were selected for
      analysis. Their clinicopathologic characteristics, postoperative outcomes, and
      survival were compared. RESULTS: There was no significant difference in
      clinicopathologic characteristics between the two propensity-matched groups.
      Median number of lymph nodes per patient was 29, and the mean number of retrieved
      lymph nodes was similar in the LATG and OTG groups (30.8+/-10.2 vs. 29.0+/-8.3).
      Peri-operative characteristics, operation time, number of transfused units per
      patient, and time to resumption of activities were similar in the two groups;
      while blood loss, times to first flatus and resumption of soft diet, and post
      operative stay were significantly lower in the LATG group (P < 0.05,
      respectively). Rates of post-operative complications (12.1% vs. 15.5%) and
      postoperative mortality (0% vs. 1.7%), as well as cumulative survival rates, were
      similar. CONCLUSIONS: LATG with D2 lymphadenectomy is a safe and feasible
      procedure for AGC patients without serosa invasion. Prospective, multicenter,
      randomized trials are needed to confirm the efficacy of LATG in this patient
      population.

PMID- 24451942
TI  - Biocompatibility, biodegradation, and neovascularization of human single-unit
      platelet-rich fibrin glue: an in vivo analysis.
AB  - BACKGROUND: The clinical applications of fibrin glue span over several surgical
      modalities. The aim of this study was to evaluate the biocompatibility and
      biodegradation of different formulations of platelet-rich fibrin glue in vivo and
      examine its effects on the neovascularization of wound sites. METHODS: Human
      derived single-unit fibrin glue was prepared. Incisions were made on the backs of
      rats, and these were coated with homemade glues containing different
      concentrations of aminomethylbenzoic acid (Groups A-F) or commercial adhesives
      (Group G). A sham control group was included (Group H). The wounds were examined
      by histological analysis and immunohistochemistry at several time points.
      RESULTS: Successful wound closure was achieved in all groups by day 12. Acute
      inflammation occurred during the first six days, but gradually disappeared. The
      longest sealant duration was achieved using the lowest concentration of anti
      fibrinolytic agent in a 1:10 volume ratio with cryoprecipitate. Expression levels
      of the platelet endothelial cell adhesion molecule-1 were significantly higher in
      Groups A and C compared to the control groups (Groups G and H) on day 3 (P <
      0.05). CONCLUSIONS: Single-unit platelet-rich fibrin glue has excellent
      biocompatibility and is associated with the upregulation of neovascularization.
      The addition of aminomethylbenzoic acid could prevent the degradation of fibrin
      glue.

PMID- 24451943
TI  - Role of polymorphisms of the IGF2 and IGFBP3 genes and risk of gastric carcinoma
      in China.
AB  - BACKGROUND: The insulin-like growth factor signaling pathway plays an important
      role in the modulation of cell growth and proliferation. The aim of this study
      was to investigate the role of polymorphisms of the insulin-like growth factor 2
      (IGF2) and IGF-binding protein 3 (IGFBP3) genes, which encode key proteins of
      this pathway, as risk factors for gastric carcinoma (GC). METHODS: A case-control
      study including 404 histologically confirmed GC patients and 424 healthy controls
      of the same ethnicity was conducted to retrospectively investigate the genetic
      polymorphisms of two genes, IGF2+820A>G (rs680) and IGFBP3 A-202C (rs2854744).
      Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
      using Logistic regression. RESULTS: The IGF2 genetic variants examined
      contributed to GC risk individually (OR, 1.26; 95% CI, 1.08-1.46). The genotype
      frequencies of IGFBP3 A-202C were not significantly different between the cancer
      cases and controls (P > 0.05). Compared to the IGF2 AA genotype, carriers of one
      variant combined genotype were more pronounced among young subjects (<60 years),
      male subjects, never smokers, and those with a family history of cancer (OR =
      1.36, 95% CI = 1.09-1.72, P < 0.05; OR = 1.61, 95% CI = 1.28-2.08, P < 0.05; OR =
      1.46, 95% CI = 1.11-1.98, P < 0.05; OR = 1.53, 95% CI = 0.91-2.6, P < 0.05;
      respectively). Moreover, when the combined effects of the risk genotypes were
      investigated, significant associations were detected between highrisk genotypes
      in IGF2 and IGFBP3 (OR, 2.47; 95% CI, 1.75-3.49). CONCLUSIONS: Our results
      suggest that polymorphic variants of the IGF2 genes modulate gastric
      carcinogenesis. Moreover, when the IGF2 and IGFBP3 variants are evaluated
      together, a greater effect on GC risk is observed.

PMID- 24451944
TI  - Effectiveness and safety of endoscopic submucosal dissection for intraepithelial
      neoplasia of the esophagogastric junction.
AB  - BACKGROUND: Endoscopic submucosal dissection of the esophagogastric junction is
      the most difficult gastric and esophageal dissection procedure. No reports of
      endoscopic submucosal dissection for Siewert type II carcinoma of the
      esophagogastric junction have compared the outcomes of endoscopic submucosal
      dissection for all three Siewert types of adenocarcinoma. This study aimed to
      evaluate the efficacy and safety of endoscopic submucosal dissection for
      intraepithelial neoplasia of the esophagogastric junction. METHODS: From October
      2008 to June 2013, 73 patients underwent endoscopic submucosal dissection for
      intraepithelial neoplasia of the esophagogastric junction. The patients were
      prospectively evaluated regarding the executability of the technique, short-term
      results of the procedure, en bloc resection rate, curative resection rate,
      complications and additional treatment after endoscopic submucosal dissection,
      and follow-up outcomes. RESULTS: Sixty-eight of the 73 patients (93.2%) underwent
      en bloc resection; the mean maximum specimen diameter was 33.7 mm. Fifty-seven of
      61 patients (93.4%) who underwent curative resection were successfully followed
      up for 1.0 to 56.0 months (average, 24.1 months). Local recurrence developed in
      one patient with high-grade intraepithelial neoplasm. Twelve patients underwent
      noncurative resection, including lateral resection margin residues in three,
      vertical resection margin residues in one, signet ring cell carcinoma or
      undifferentiated adenocarcinoma in four, lymphatic or vessel invasion in one,
      vertical residual margin residues combined with signet ring cell carcinoma in
      one, and undifferentiated adenocarcinoma with lymphatic or vessel invasion in
      two. In the noncurative resection group, one patient was lost to follow-up, seven
      underwent additional surgery, and the remaining four were periodically followed
      up; none had local recurrence or distant metastases. The only complication was
      delayed bleeding in three patients, which was successfully controlled by
      conservative treatment or endoscopic therapy. CONCLUSIONS: Endoscopic submucosal
      dissection is safe and effective for intraepithelial neoplasia of the
      esophagogastric junction. R0 en bloc resection is possible and can avoid the risk
      of local recurrence.

PMID- 24451945
TI  - Role of paxillin in colorectal carcinoma and its relationship to
      clinicopathological features.
AB  - BACKGROUND: Colorectal carcinoma is one of the most common malignant tumors.
      Despite advances in therapy, mortality is still very high. The aim of this study
      was to evaluate the expression of paxillin in the human colon adenocarcinoma cell
      line SW480 and its role in cell cycle and apoptosis. We also investigated the
      expression of paxillin in colorectal carcinoma tissues and its relationship to
      clinicopathological features and survival. METHODS: Paxillin short hairpin RNA
      (shRNA) was constructed and transfected into the colon adenocarcinoma cell line
      SW480. The influence of paxillin shRNA on the cell cycle and cell apoptosis was
      analyzed by flow cytometry. Immunohistochemistry staining was used to assess the
      expression of paxillin and its association with the expression of
      carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, p53 and Bcl-2 in
      102 patients with primary colorectal carcinoma. Western blotting was also used to
      investigate the expression of paxillin. Medical records were reviewed and a
      clinicopathological analysis was performed. RESULTS: In vitro, the percentage of
      cells in S phase was (45.23+/-1.05)%, (43.53+/-1.23)%, and (36.13+/-0.57)% in the
      blank control group, negative control group, and paxillin shRNA group
      respectively. It was significantly decreased in the paxillin shRNA group (P =
      0.000). The early apoptosis index of the paxillin shRNA group (17.2+/-1.18%) was
      significantly increased compared to the control shRNA group ((13.17+/-1.15)%, P =
      0.013). Paxillin was positive in 71 (69.6%) patients, and it was found to be
      overexpressed in tumor tissues compared with normal adjacent tissues. Paxillin
      positive rate was higher in patients who are less than 50-years old (100.0% vs.
      65.6%, P = 0.016). Paxillin expression was associated with a high histologic
      grade of carcinoma (81.4% vs. 61.0%, P = 0.031), a high rate of regional lymph
      node metastasis (22.5% vs. 13.0%, P = 0.031), mesenteric artery lymph node
      metastasis (100.0% vs. 64.8%, P = 0.008), distant metastasis (94.1% vs. 64.7%, P
      = 0.016) and a high Tumor Node Metastasis (TNM) stage (94.1%, 73.2%, 60.0%, and
      50%, P = 0.030). Multivariate analyses revealed that recurrence was associated
      with the rate of regional lymph node metastasis (P = 0.001) and paxillin
      expression (P = 0.024). Multivariate analysis indicated that the overall survival
      is related to the TNM stage (P = 0.000). CONCLUSIONS: In vitro, paxillin may
      promote cell proliferation and inhibit apoptosis in SW480 cells. Paxillin may be
      a potential metastasis predictor, and an independent prognosis factor of
      recurrence. It may also be related to poor patient outcomes, but was not an
      independent predictor of survival.

PMID- 24451946
TI  - A single center experience: post-transplantation adjuvant chemotherapy impacts
      the prognosis of hepatocellular carcinoma patients.
AB  - BACKGROUND: The aim of this research was to investigate the impact of post
      transplantation adjuvant chemotherapy in the prevention of tumor recurrence and
      metastasis for hepatocellular carcinoma (HCC) exceeding Milan criteria after
      liver transplantation. METHODS: A total of 117 patients with HCC exceeding the
      Milan criteria who had undergone orthotopic liver transplantation (OLT) from
      August 2002 to February 2009 were enrolled and retrospectively analyzed. The
      patients were divided into four groups according to chemotherapy regimens and the
      impact of different chemotherapy regimens on survival, disease-free survival, and
      adverse effects were compared. RESULTS: One year survival rates for the
      gemicitabine, conventional chemotherapy, oxaliplatin plus capecitabine and the
      best supportive care (BSC) group were 87.5%, 84.2%, 81.6%, and 67.5%. The 3-year
      survival rates were 48.1%, 25.9%, 31.6%, and 33.7%, respectively for the four
      groups. One year disease free survival rates for the four groups were 69.8%,
      47.4%, 53.8%, and 45.7% respectively. And 3-year disease free survival rates were
      43.2%, 23.7%, 23.6%, and 25.1% for the four groups. Stratification analysis
      showed that the gemcitabine regimen and conventional chemotherapy could
      significantly improve the survival rate and disease free survival rate for HCC
      patients who had major vascular invasion and/or microvascular invasion after
      liver transplantation compared with BSC group. CONCLUSIONS: For HCC patients
      beyond Milan criteria, especially who had vascular invasion and/or micorvascular
      invasion, post-transplantation adjuvant chemotherapy can significantly improve
      survival. Gemcitabine is a proper regimen for postoperative adjuvant
      chemotherapy. Conventional chemotherapy can also benefit patients, but the
      adverse effects are not satisfactory.

PMID- 24451947
TI  - Evaluation of para-aortic nodal dissection for locoregionally advanced gastric
      cancer with 1-3 involved para-aortic nodes.
AB  - BACKGROUND: Prophylactic para-aortic nodal dissection (PAND) has no proven
      benefits for potentially curable advanced gastric cancer. However, the value of
      therapeutic PAND for involved para-aortic nodes (PANs) in patients with locally
      advanced gastric cancers has not been determined yet. METHODS: Between 1998 and
      2010, 157 gastric cancer patients with 1-3 involved PANs underwent extended D2
      (D2+) lymphadenectomy plus PAND (PAND group, n = 69) or extended D2
      lymphadenectomy alone (non-PAND group, n = 88). The clinicopathologic features
      and prognostic data were compared between the two groups. A propensity score
      adjusted analysis was used for a balanced comparison. RESULTS: The rate of PAN
      metastasis was 40.6% (28/69) in the PAND group. The 5-year survival rate was
      significantly higher in the PAND group than in the non-PAND group (43.7% vs.
      31.8%, P = 0.044). Compared to the non-PAND group, the death hazard ratios in the
      PAND group were 0.45 (95% CI 0.274-0.739; P = 0.002) and 0.536 (95% CI 0.328
      0.861; P = 0.0097) by multivariate analysis without and with propensity score
      adjustment respectively. Recurrence rate at 5 years was 39.1% in the PAND group
      and 43.2% in the non-PAND group (P = 0.628). CONCLUSION: Extended D2
      lymphadenectomy plus PAND is associated with superior outcomes for advanced
      gastric cancer patients with 1-3 involved PANs.

PMID- 24451948
TI  - Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.
AB  - BACKGROUND: Paclitaxel (PAC) is the first-line chemotherapy drug for most breast
      cancer patients, but clinical studies showed that some breast cancer patients
      were insensitive to PAC, which led to chemotherapy failure. It was reported that
      Notch1 signaling participated in drug resistance of breast cancer. Here, we show
      whether Notch1 expression is related to PAC sensitivity of breast cancer.
      METHODS: We employed Notch1 siRNA and Notch1 inhibitor, N-[N-(3,5
      difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT), to down
      regulate Notch1 expression in human breast cancer cells MDA-MB-231, and detected
      the inhibition effect by Western blotting and reverse trans cription-polymerase
      chain reaction, respectively. After 24 hours exposure to different concentration
      of PAC (0, 1, 5, 10, 15, 20, and 25 ug/ml), the viability of the control group
      and experimental group cells was tested by MTT. We also examined the expression
      of Notch1 in PAC sensitive and nonsensitive breast cancer patients, respectively
      by immunohistochemistry (IHC). The PAC sensitivity of breast cancer patients were
      identified by collagen gel droplet embedded culture-drug sensitivity test (CD
      DST). RESULTS: Down regulation of Notch1 expression by Notch1siRNA interference
      or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P < 0.05).
      Also, the expression of Notch1 in PAC sensitive patients was much lower than that
      of PAC non-sensitive patients (P < 0.01). CONCLUSION: Notch1 expression has an
      effect on PAC sensitivity in breast cancer patients, and the inhibition of Notch1
      increases paclitaxel sensitivity to human breast cancer.

PMID- 24451950
TI  - A two-year follow-up for Chinese patients with abdominal aortic aneurysm
      undergoing open/endovascular repair.
AB  - BACKGROUND: A number of studies have demonstrated the rates of overall and
      aneurysm-related mortality and morbidity in Western populations. The
      cardiovascular risk factors influencing postoperative outcome have been also
      reported. Until recently, little has been known about the prognosis in this
      patient cohort in the Chinese population. We evaluated the independent predictors
      of mortality and morbidity in abdominal aortic aneurysm (AAA) patients undergoing
      elective surgical treatment and emphasized whether the coronary artery
      revascularization could have any effect on the overall mortality and morbidity in
      patients following the current guideline recommendation. METHODS: A total of 386
      patients (174 women) undergoing surgery in Beijing Anzhen Hospital from January
      2008 to June 2010 were enrolled (mean age (70.6+/-10.5) years). Kaplan-Meier
      curves were constructed to compare the mortality and morbidity of AAA patients
      with coronary artery revascularization and those without. A Cox proportional
      hazards model was constructed to identify clinical factors associated with two
      year outcomes. The primary outcomes were death from any cause, the pre-specified
      morbidity was re-hospitalization for pulmonary conditions, congestive heart
      failure, angina, ischemic/hemorrhagic stroke. RESULTS: During the two-year follow
      up, 34 patients died and 65 experienced re-hospitalization with pulmonary
      conditions, congestive heart failure, angina, or ischemic/hemorrhagic stroke.
      Kaplan-Meier survival analysis showed that the AAA patients with cardiac
      revascularization had no higher incidence of overall mortality and major
      morbidity than those without (log-rank test P = 0.35 and P = 0.40, respectively).
      Cox proportional hazards regression analysis showed that level of lowdensity
      lipoprotein (HR, 4.06; 95% CI: 1.19-18.7, P = 0.027) and AAA size (HR, 2.18; 95%
      CI: 1.28-11.65, P = 0.036) were independently associated with the incidence of
      overall mortality. Long-term use of angiotensin converting enzyme inhibitors,
      statins, AAA size and systolic blood pressure were independent predictors of the
      secondary pre-specified outcomes. CONCLUSIONS: Coronary artery revascularization
      following the guideline recommendations did not increase the mortality and
      morbidity of Chinese with AAA who were undergoing repair. Absence of angiotensin
      converting enzyme inhibitors and statins, AAA size, and systolic blood pressure
      were powerful predictors of the clinical events.

PMID- 24451949
TI  - Construction of the Chinese Veteran Clinical Research (CVCR) platform for the
      assessment of non-communicable diseases.
AB  - BACKGROUND: Based on the excellent medical care and management system for Chinese
      veterans, as well as the detailed medical documentation available, we aim to
      construct a Chinese Veteran Clinical Research (CVCR) platform on non-communicable
      diseases (NCDs) and carry out studies of the primary disabling NCDs. METHODS: The
      Geriatric Neurology Department of Chinese People's Liberation Army General
      Hospital and veterans' hospitals serve as the leading and participating units in
      the platform construction. The fundamental constituents of the platform are
      veteran communities. Stratified typical cluster sampling is adopted to recruit
      veteran communities. A cross-sectional study of mental, neurological, and
      substance use (MNS) disorders are performed in two stages using screening scale
      such as the Mini-Mental State Examination and Montreal cognitive assessment,
      followed by systematic neuropsychological assessments to make clinical diagnoses,
      evaluated disease awareness and care situation. RESULTS: A total of 9 676 among
      277 veteran communities from 18 cities are recruited into this platform, yielding
      a response rate of 83.86%. 8 812 subjects complete the MNS subproject screening
      and total response rate is 91.70%. The average participant age is (82.01+/-4.61)
      years, 69.47% of veterans are 80 years or older. Most participants are male
      (94.01%), 83.36% of subjects have at least a junior high school degree. The
      overall health status of veterans is good and stable. The most common NCD are
      cardiovascular disorders (86.44%), urinary and genital diseases (73.14%), eye and
      ear problems (66.25%), endocrine (56.56%) and neuro-psychiatric disturbances
      (50.78%). CONCLUSION: We first construct a veterans' comprehensive clinical
      research platform for the study of NCDs that is primarily composed of highly
      educated Chinese males of advanced age and utilize this platform to complete a
      cross-sectional national investigation of MNS disorders among veterans. The good
      and stable health condition of the veterans could facilitate the long-term follow
      up studies of NCDs and provide prospective data to the prevention and management
      of NCDs.

PMID- 24451951
TI  - Automated brain tumor segmentation in magnetic resonance imaging based on sliding
      window technique and symmetry analysis.
AB  - BACKGROUND: Brain tumor segmentation from magnetic resonance imaging (MRI) is an
      important step toward surgical planning, treatment planning, monitoring of
      therapy. However, manual tumor segmentation commonly used in clinic is time
      consuming and challenging, and none of the existed automated methods are highly
      robust, reliable and efficient in clinic application. An accurate and automated
      tumor segmentation method has been developed for brain tumor segmentation that
      will provide reproducible and objective results close to manual segmentation
      results. METHODS: Based on the symmetry of human brain, we employed sliding
      window technique and correlation coefficient to locate the tumor position. At
      first, the image to be segmented was normalized, rotated, denoised, and bisected.
      Subsequently, through vertical and horizontal sliding-windows technique in turn,
      that is, two windows in the left and the right part of brain image moving
      simultaneously pixel by pixel in two parts of brain image, along with calculating
      of correlation coefficient of two windows, two windows with minimal correlation
      coefficient were obtained, and the window with bigger average gray value is the
      location of tumor and the pixel with biggest gray value is the locating point of
      tumor. At last, the segmentation threshold was decided by the average gray value
      of the pixels in the square with center at the locating point and 10 pixels of
      side length, and threshold segmentation and morphological operations were used to
      acquire the final tumor region. RESULTS: The method was evaluated on 3D FSPGR
      brain MR images of 10 patients. As a result, the average ratio of correct
      location was 93.4% for 575 slices containing tumor, the average Dice similarity
      coefficient was 0.77 for one scan, and the average time spent on one scan was 40
      seconds. CONCLUSIONS: An fully automated, simple and efficient segmentation
      method for brain tumor is proposed and promising for future clinic use.
      Correlation coefficient is a new and effective feature for tumor location.

PMID- 24451952
TI  - Cigarette smoking contributes to idiopathic pulmonary fibrosis associated with
      emphysema.
AB  - BACKGROUND: Combined emphysema and pulmonary fibrosis, including idiopathic
      pulmonary fibrosis (IPF), is a distinct disorder described with upper-lobe
      emphysema and lower-lobe fibrosis on chest computed tomography. Smoking appears
      to be the predominant risk factor for this disorder. We aimed to compare clinical
      features, smoking history, physiological and radiological findings between IPF
      with and without emphysema. METHODS: A sample of 125 IPF patients over a period
      of 48 months were evaluated. High resolution CT scans were reviewed blinded to
      clinical data. The IPF patients with or without emphysema were classified
      accordingly. RESULTS: The prevalence of emphysema in this IPF sample was 70/125.
      IPF with emphysema was significantly associated with smoking status (OR 63; 95%
      CI 4.4 to 915; P = 0.002) and smoking pack year (OR 1.1; 95% CI 1.05 to 1.13; P =
      0.000). The patients with IPF and emphysema had a higher decrease in carbon
      monoxide diffusing capacity adjusted for alveolar volume ((58+/-19)% pred vs.
      (66+/-21)% pred; P = 0.021) and a higher prevalence of pulmonary hypertension
      (24/70 vs. 7/55; P = 0.006). The two groups of patients had similar forced and
      residual volumes. No significant differences were found in cell differentials of
      bronchoalveolar lavage or the scores of fibrosis on chest CT. Survival of the
      patients with emphysema was significantly less than that of patients with IPF
      alone. CONCLUSIONS: Cigarette smoking induces IPF combined with emphysema.
      Emphysema further impairs physiological function and increases the prevalence of
      pulmonary hypertension that leads to poor prognosis. The inclusion of the
      patients with combined pulmonary fibrosis and emphysema in IPF clinical trials
      may lead to under evaluation of the effect of treatment in patients.

PMID- 24451953
TI  - Allogeneic compact bone-derived mesenchymal stem cell transplantation increases
      survival of mice exposed to lethal total body irradiation: a potential
      immunological mechanism.
AB  - BACKGROUND: Radiation-induced injury after accidental or therapeutic total body
      exposure to ionizing radiation has serious pathophysiological consequences, and
      currently no effective therapy exists. This study was designed to investigate
      whether transplantation of allogeneic murine compact bone derived-mesenchymal
      stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage
      total body irradiation (TBI), and to explore the potential immunoprotective role
      of MSCs. METHODS: BALB/c mice were treated with 8 Gy TBI, and then some were
      administered CB-MSCs isolated from C57BL/6 mice. Survival rates and body weight
      were analyzed for 14 days post-irradiation. At three days post-irradiation, we
      evaluated IFN-gamma and IL-4 concentrations; CD4(+)CD25(+)Foxp3(+) regulatory T
      cell (Treg) percentage; CXCR3, CCR5, and CCR7 expressions on CD3(+) T cells; and
      splenocyte T-bet and GATA-3 mRNA levels. CB-MSC effects on bone marrow
      hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM)
      assay. RESULTS: After lethal TBI, compared to non-transplanted mice, CB-MSC
      transplanted mice exhibited significantly increased survival, body weight, and
      CFU-GM counts of bone marrow cells (P < 0.05), as well as higher Treg
      percentages, reduced IFN-gamma, CXCR3 and CCR5 down-regulation, and CCR7 up
      regulation. CB-MSC transplantation suppressed Th1 immunity. Irradiated
      splenocytes directly suppressed CFU-GM formation from bone marrow cells, and CB
      MSC co-culture reversed this inhibition. CONCLUSION: Allogeneic CB-MSC
      transplantation attenuated radiation-induced hematopoietic toxicity, and provided
      immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition, expanding
      Tregs, regulating T cell chemokine receptor expressions, and skewing the Th1/Th2
      balance toward anti-inflammatory Th2 polarization.

PMID- 24451954
TI  - Effect of two volume responsiveness evaluation methods on fluid resuscitation and
      prognosis in septic shock patients.
AB  - BACKGROUND: Few studies have reported the effect of different volume
      responsiveness evaluation methods on volume therapy results and prognosis. This
      study was carried out to investigate the effect of two volume responsiveness
      evaluation methods, stroke volume variation (SVV) and stroke volume changes
      before and after passive leg raising (PLR-DeltaSV), on fluid resuscitation and
      prognosis in septic shock patients. METHODS: Septic shock patients admitted to
      the Department of Critical Care Medicine of Zhejiang Hospital, China, from March
      2011 to March 2013, who were under controlled ventilation and without arrhythmia,
      were studied. Patients were randomly assigned to the SVV group or the PLR-DeltaSV
      group. The SVV group used the Pulse Indication Continuous Cardiac Output
      monitoring of SVV, and responsiveness was defined as SVV >=12%. The PLR-DeltaSV
      group used DeltaSV before and after PLR as the indicator, and responsiveness was
      defined as DeltaSV >=15%. Six hours after fluid resuscitation, changes in tissue
      perfusion indicators (lactate, lactate clearance rate, central venous oxygen
      saturation (SCVO2), base excess (BE)), organ function indicators (white blood
      cell count, neutrophil percentage, platelet count, total protein, albumin,
      alanine aminotransferase, total and direct bilirubin, blood urea nitrogen, serum
      creatinine, serum creatine kinase, oxygenation index), fluid balance (6- and 24
      hour fluid input) and the use of cardiotonic drugs (dobutamine), prognostic
      indicators (the time and rate of achieving early goal-directed therapy (EGDT)
      standards, duration of mechanical ventilation and intensive care unit stay, and
      28- day mortality) were observed. RESULTS: Six hours after fluid resuscitation,
      there were no significant differences in temperature, heart rate, blood pressure,
      SpO2, organ function indicators, or tissue perfusion indicators between the two
      groups (P > 0.05). The 6- and 24-hour fluid input was slightly less in the SVV
      group than in the PLR-DeltaSV group, but the difference was not statistically
      significant (P > 0.05). The SVV group used significantly more dobutamine than the
      PLR-DeltaSV group (33.3% vs. 10.7%, P = 0.039). There were no significant
      differences in the time ((4.8+/-1.4) h vs. (4.3+/-1.3) h, P = 0.142) and rate of
      achieving EGDT standards (90.0% vs. 92.9%, P = 0.698), or in the length of
      mechanical ventilation and ICU stay. The 28-day mortality in the SVV group (16.7%
      (5/30)) was slightly higher than the PLR-?SV group (14.3% (4/28)), but the
      difference was not statistically significant (P = 0.788). CONCLUSIONS: In septic
      shock patients under controlled ventilation and without arrhythmia, using SVV or
      PLR-DeltaSV methods to evaluate volume responsiveness has a similar effect on
      volume therapy results and prognosis. The evaluation and dynamic monitoring of
      volume responsiveness is more important for fluid resuscitation than the
      evaluation methods themselves. Choosing different methods to evaluate volume
      responsiveness has no significant influence on the effect of volume therapy and
      prognosis.

PMID- 24451955
TI  - High expression of follicle stimulating hormone receptor in testicular tissue of
      idiopathic azoospermic patients with severe spermatogenic defects.
AB  - BACKGROUND: Follicle stimulating hormone is necessary for normal reproduction in
      men. The biochemical actions of follicle stimulating hormone result from binding
      to the follicle stimulating hormone receptor in the plasma membrane of Sertoli
      cells. Here, we investigated the expression of the follicle stimulating hormone
      receptor in different testicular histological phenotypes of patients with
      idiopathic azoospermia. METHODS: Fifty-seven cases of idiopathic azoospermia were
      classified into three groups according to the results of testicular biopsy:
      patients with hypospermatogenesis, patients with maturation arrest, and patients
      with Sertoli cell-only syndrome. Thirteen azoospermic patients identified by
      testicular biopsy as being capable of completing spermatogenesis acted as the
      control group. Immunohistochemistry and real-time quantitative reverse
      transcriptase polymerase chain reaction were performed in each case, and the
      serum hormone level was also measured in all patients. RESULTS: The serum
      follicle stimulating hormone level in patients with Sertoli cell-only syndrome
      was significantly higher than in patients with hypospermatogenesis, maturation
      arrest, and complete spermatogenesis (P < 0.01). The serum follicle stimulating
      hormone level in patients with maturation arrest was significantly higher than in
      patients with hypospermatogenesis and complete spermatogenesis (P < 0.05). There
      was no difference in serum follicle stimulating hormone levels in patients with
      hypospermatogenesis and complete spermatogenesis. The follicle stimulating
      hormone receptor expression level of testicular samples with Sertoli cell-only
      syndrome was significantly higher than in those with hypospermatogenesis,
      maturation arrest, and complete spermatogenesis (P < 0.05), but no significant
      difference was observed among hypospermatogenesis, maturation arrest, and
      complete spermatogenesis testicular samples. CONCLUSIONS: Different serum
      follicle stimulating hormone levels and follicle stimulating hormone receptor
      expression were found in the different testicular histology phenotypes in
      azoospermic patients. Differential follicle stimulating hormone receptor
      expression in testicular tissue of patients with idiopathic azoospermia may be
      associated with the degree of spermatogenesis.

PMID- 24451956
TI  - Shortening of the 3' untranslated region: an important mechanism leading to
      overexpression of HMGA2 in serous ovarian cancer.
AB  - BACKGROUND: Oncofetal protein high-mobility-group AT-hook protein 2 (HMGA2) is
      reactivated in serous ovarian cancer (SOC) and its overexpression correlates with
      poor prognosis. To explore the mechanism, we investigated whether HMGA2 could
      avoid microRNA regulation due to gene truncation or 3' UTR shortening by
      alternative polyadenylation. METHODS: Real-time reverse transcription polymerase
      chain reaction (RT-PCR) was used to evaluate the abundance of different regions
      of HMGA2 mRNA in 46 SOC samples. Rapid amplification of cDNA 3' ends (3' RACE)
      and Southern blotting were used to confirm the shortening of 3' untranslated
      region (UTR). 5' RACE and Southern blotting were used to prove the mRNA decay.
      RESULTS: No significant difference in the ratio of the stable coding region to
      the fragile region was observed between SOC and control normal fallopian tubes,
      indicating that the HMGA2 gene is not truncated in SOC. Varying degrees of 3' UTR
      shortening in SOC samples were observed by comparing the abundance of the
      proximal region and distal region of the HMGA2 3' UTR. The ratio of the proximal
      to the distal region of the 3' UTR correlated significantly with expression of
      the HMGA2 coding region in SOC (r = 0.579, P < 0.01). Moreover, although the
      abundance of the HMGA2 coding region varied, all samples, including the very low
      expressed samples, exhibit relatively high levels of the proximal 3' UTR region,
      suggesting a dynamic decay of HMGA2 mRNA from the 5' end. The shortening of 3'
      UTR and the decay from the 5' end were confirmed by 3' RACE, 5' RACE and
      subsequent Southern blotting. CONCLUSION: Heterogeneous 3' UTR lengths render
      HMGA2 susceptible to different levels of negative regulation by microRNAs, which
      represents an important mechanism of HMGA2 reactivation in SOC.

PMID- 24451957
TI  - Advancement of maxillary anterior segment by distraction osteogenesis for severe
      maxillary retrusion in cleft lip and palate.
AB  - BACKGROUND: Maxillary anterior segmental distraction osteogenesis (MASDO) is a
      recently used method for correction of severe maxillary retrusion in cleft lip
      and palate (CLP) patients. In this article, we evaluated the feasibility of MASDO
      using rigid external distraction (RED) and rapid orthodontic tooth movement to
      correct severe maxillary retrusion in CLP patients. METHODS: Fourteen male and
      five female complete CLP patients between the ages of 18 and 22 years (mean age
      19.7 years) at the time of distraction, with severe maxillary retrusion, were
      treated with the rigid external distraction (RED) device after maxillary anterior
      osteotomy. Rapid orthodontic tooth movement was started one week after the MASDO.
      Standard profile photographic, cephalometric films were obtained preoperatively
      and after therapy. Sella-nasion-point A (SNA) and Sella-nasion-point B (SNB)
      angles were measured to reflect changes in maxillary and mandibular position, and
      the distance between anterior nasal spine and posterior nasal spine (ANS-PNS) was
      measured to represent the maxillary dental arch length. RESULTS: The SNA angle
      increased from an average of 74.6 degrees  (range 73.0 degrees -78.0 degrees ),
      preoperatively, to 83.4 degrees  (range 78.6 degrees -88.0 degrees ) after the
      RED was removed (P < 0.01). All cases of severe maxillary retrusion were
      improved. Nine patients' profiles became harmonious after therapy. One patient
      had a bimaxillary protrusion deformity and needed further surgery. The regenerate
      alveolar crest and edentulous space on both segments was almost completely
      eliminated after rapid orthodontic tooth movement. CONCLUSION: MASDO with the RED
      system and rapid orthodontic tooth movement is a successful way of correcting
      severe maxillary retrusion in CLP patients.

PMID- 24451958
TI  - Current status of pediatric kidney transplantation in China: data analysis of
      Chinese Scientific Registry of Kidney Transplantation.
AB  - BACKGROUND: Kidney transplantation (KTx) is the primary therapy for children with
      renal failure. Unlike KTx in adult patients, it is commonly agreed that pediatric
      KTx in China is far behind that of America. There has been no systematic analysis
      of Chinese pediatric KTx reported. This study aimed to demonstrate the current
      status of pediatric KTx in China. METHODS: Registry data of pediatric KTx (1983
      2012) from Chinese Scientific Registry of Kidney Transplantation (CSRKT) were
      retrospectively analyzed. RESULTS: There were 851 pediatric KTx from 102
      transplant units. The recipients were (15.4+/-2.5) years of age, 93.9% of who
      were over 10 years old. Chronic glomerulonephritis and pyelonephritis accounted
      for 75.6% of recognized primary diseases. Allografts were from deceased donors
      (72.2%) or living donation (27.7%). The patient survival for 1, 3, 5, and 10
      years was 96.9%, 94.2%, 92.3%, and 92.3% and the graft survival was 94.6%, 91.4%,
      86.3%, and 79.2%, respectively. The majority of post-transplant complications
      were acute rejection and infections. Annual transplant reached the peak in 2008
      (n = 114), and decreased sharply in 2006 (n = 41) and 2010 (n = 57). The
      percentage of pediatric KTx in total KTx was highest in 2007 (1.95%) and
      decreased to trough level in 2010 (1.0%). Living donation increased by 32.5-folds
      from 2004 to 2008 and then decreased by 86.6% till 2010. The percentage of living
      donation in pediatric or total KTx dynamically changed in a similar manner, while
      living donation ratio in pediatric KTx was much higher. CONCLUSIONS: Kidney
      transplant can provide long-term benefits to pediatric recipients. Rejection and
      infections are worthy of concern during follow-up. Pediatric kidney transplant in
      China is very much lagging behind that in developed countries. Living donation
      played an important role in its development in the past decades. New strategies
      for implementation are encouraged to increase the priority of uremic children in
      organ allocation so as to promote its progress in China.

PMID- 24451959
TI  - Resolvin-D1 inhibits interleukin-8 and hydrogen peroxide production induced by
      cigarette smoke extract in 16HBE cells via attenuating NF-kappaB activation.
AB  - BACKGROUND: Cigarette smoke induced airway inflammation plays a role in
      pathogenesis of airway inflammation. Resolvin-D1 derived from omega-3
      polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolving
      lipid mediator. Resolvin-D1 ameliorated inflammatory responses in lung injury,
      asthma, peritonitis and atherosclerosis. We investigated whether resolvin-D1
      suppressed the productions of chemokines and oxidative stress induced by
      cigarette smoke extract (CSE) in vitro and its possible mechanism. METHODS: We
      examined the proinflammatory chemokine interleukin-8 and hydrogen peroxide (H2O2)
      productions induced by CSE in 16 human bronchial epithelial (16HBE) cells after
      resolvin-D1 treatment and their mechanisms. 16HBE cells were treated with
      resolvin-D1 at up to 10 nmol/L, for 30 minutes before CSE up to 16% (v/v)
      exposure. Release of interlukin-8 proteins was assessed by enzyme linked
      immunosort assay (ELISA) and its mRNA level by RT-PCR. We evaluated extracellular
      H2O2 expression in the supernatant. Phosphorylation of NF-kappaB/p65 and
      degradation of I-kappaB in 16HBE cells were determined by Western blotting
      analysis and NF-kappaB DNA binding activity by electrophoretic mobility shift
      assay (EMSA). RESULTS: 16HBE cells treated with 8% CSE showed significantly
      higher interlukin-8 production. Resolvin-D1 pretreatment inhibited CSE induced
      interlukin-8 production (mRNA and protein) in a dose and time dependent manner.
      Extracellular H2O2 level decreased after resolvin-D1 treatment. Resolvin-D1
      attenuated CSE triggered I-kappaB degradation and NF-kappaB/p65 activation dose
      dependently and inhibited NF-kappaB DNA binding activity. CONCLUSION: Resolvin-D1
      inhibits CSE induced interlukin-8 and H2O2 production in 16HBE cells by
      modulating NF-kappaB activation and has therapeutic potential for pulmonary
      inflammation.

PMID- 24451960
TI  - Optimal time to use low molecular weight heparin on prethrombotic state of rat
      chronic obstructive pulmonary disease model.
AB  - BACKGROUND: Low molecular weight heparin (LMWH), as one of anticoagulant drugs,
      has been used for the treatment of chronic obstructive pulmonary disease (COPD)
      with prethrombotic state, but the specific use time is unclear. The aim of the
      study is to observe the effect of LMWH at two different periods of prethrombotic
      state in COPD in rats and to find the optimal time to use LMWH. METHODS: Forty
      Wistar rats were randomly divided into 4 groups: normal control, raised for 55
      days without any treatment; COPD control without LMWH, cigarette inhalation plus
      intratracheal instillation of lipopolysaccharide and hypodermic injection of
      normal saline once a day for 10 days; COPD control given LMWH 150 U/kg
      subcutaneous injection, once a day for 10 days starting day 15 (LMWH-d15); COPD
      control given LMWH 150 U/kg subcutaneous injection, once a day for 10 days
      starting day 29 (LMWH-d29). RESULTS: Comparing LMWH-d15 with LMWH-d29, plasma
      viscosity, whole blood viscosity, von Willebrand factor, serum fibrinogen,
      plasminogen activator inhibitor-1 and fibrin D-dimer were each significantly
      reduced; but thrombin plasminogen activator increased significantly whilst
      arterial PO2 and PCO2 improved significantly. CONCLUSION: The better time to use
      LMWH is the time when coagulation and fibrinolytic indices begin to change in
      COPD.

PMID- 24451961
TI  - In vivo detection of severity of optic nerve crush using manganese-enhanced
      magnetic resonance imaging in rats.
AB  - BACKGROUND: Traumatic optic neuropathy (TON) is one of the reasons for permanent
      vision loss. Currently, the clinical practices may not be sufficient for direct
      assessments and comprehensively determining the location and extent of the
      patients with optic nerve injury in traumatic optic neuropathy. Magnetic
      resonance imaging (MRI) provides a non-invasive option. However, rare reports
      have found whether the differentdegree of injury of the optic nerve can be
      detected by manganese-enhanced MRI (MEMRI). This study aimed to explore the
      efficacy of MEMRI in the visual pathway for different severity of opitic nerve
      injury in rats. METHODS: The different injuries of mild, moderate, and heavy
      damages were created by modified reverse tweezer and were evaluated by counting
      retinal ganglion cells (RGCs) and VEP ananlysis. Sprague-Dawley (SD) rats were
      intravitreally injected with 2 l of 25 mmol/L MnCl2, which has been confirmed as
      a safe injection concentration. The contrast-to-noise ratio (CNR) of MEMRI for
      optic nerve enhancement at different injury levels was measured. RESULTS: The
      location of the significantly decreased signal point on optic nerve (ON) was
      corresponding to the location we made. However, similar findings are not obvious,
      or even have not been observed in 28 days in each group and also in 14 days at
      F100 group, indicating that MEMRI could be directly intuitive positioned in the
      early stage on the optic nerve injury. CONCLUSIONS: The possibility of using
      MEMRI in optic nerve injury in a safe injection concentration of 25 mmol/L is
      confirmed. Therefore, it is possible to detect the severity of the optic nerve by
      MEMRI examination.

PMID- 24451962
TI  - Emergence of Klebsiella pneumoniae carbapenemase-producing Escherichia coli
      sequence type 131 in Hangzhou, China.
AB  - BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia (E.)
      coli has been reported in China since 2008. However, there is no information
      about the molecular epidemiology of KPC-producing E. coli in China. In this
      study, we aimed to investigate the sequence type (ST) and characteristics of KPC
      producing E. coli isolates in China. METHODS: Three carbapenem-resistant isolates
      of E. coli (E1, E2, and E3) from one teaching hospital in Hangzhou covering a one
      year period were analyzed. Antibiotic susceptibility was determined by Etest.
      Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST)
      were used for epidemiological analysis. The genetic structure around blaKPC, the
      major plasmid incompatibility typing, and the identification of beta-lactamase
      gene types were performed by PCR and the positive products were subsequently
      sequenced. Plasmids were analyzed by transformation, restriction, and Southern
      blotting. RESULTS: PFGE demonstrated that patterns of isolates E1 and E2 were
      clonally-related and designated as patterns A1 and A2; pattern of isolate E3 was
      different and designated as pattern B. MLST analysis showed that the three
      isolates displayed one common sequence type ST131. The identification of bla gene
      types by PCR and sequencing showed that blaKPC-2, blaCTX-M-14, and blaTEM-1 were
      detected in all three isolates. All three isolates carried a KPC-2-encoding
      plasmid of the IncN replicon. Plasmid analysis and hybridization experiments
      showed that the isolates were found simultaneously to carry two or four plasmids.
      The blaKPC-2 gene in E1 and E2 was located in a plasmid with size of ca. 50 kb.
      However, the blaKPC-2 gene in E3 was located in a plasmid with size of ca. 130
      kb. CONCLUSIONS: E. coli ST131 with KPC-2 beta-lactamase has emerged in China,
      which enlarges the geographical area where the ST131 KPC-producing E. coli
      strains have diffused.

PMID- 24451963
TI  - Age-related white matter degradation rule of normal human brain: the evidence
      from diffusion tensor magnetic resonance imaging.
AB  - BACKGROUND: Diffusion tensor imaging can evaluate white matter function in human
      brain. Fractional anisotropy is the most important parameter. This study aimed to
      find regional reduction of fractional anisotropy (FA) with aging in the whole
      brain and the changing rules of anisotropy with aging. METHODS: Fifty volunteers
      from 20 to 75 years old were divided into five consecutive age groups; a young
      group and four senior groups. FA values were calculated with diffusion tensor
      imaging (DTI) studio software. The difference of FA between the young group and
      the four senior groups were analyzed by analysis of voxel-level height threshold
      in Statistic Parametric Mapping (SPM), and the regions with decreased FA were
      obtained. The FA values of these regions were then extracted using an in-house
      developed program, and a multiple linear regression model was built to assess the
      influence of age and sex on the FA values of these regions. RESULTS: Eight
      regions, including frontal lobe, postcentral gyrus, optic radiation, hippocampus,
      cerebella hemisphere, corona radiate, corpus callosum and internal capsule, were
      found to have decreased FA. There was a strong negative correlation between age
      and the FA in the frontal lobe, postcentral gyrus, optic radiation, hippocampus,
      and cerebella hemisphere, while a weaker negative correlation in the corona
      radiate, corpus callosum, and internal capsule was found. The FA reduction in the
      frontal lobe, postcentral gyrus, optic radiation, hippocampus and cerebella
      hemisphere were found earlier than in the corona radiate, corpus callosum and
      internal capsule. There was no correlation between sex and FA in these regions.
      CONCLUSIONS: The FA in the subcortical white matter area reduces earlier than
      that in deep white matter. The areas with decreased FA continuously enlarge with
      aging. The FAs in these regions have a strong negative correlation with age.

PMID- 24451965
TI  - Current practice of gastric cancer treatment.
AB  - OBJECTIVE: The aim of this review was to overview the current practice of gastric
      cancer treatment including surgery and other adjuvant modalities. DATA SOURCES:
      The review was based on data obtained from the published articles and main
      guidelines in the East and West. STUDY SELECTION: Articles with high level of
      evidence or current best evidence in each issue were selected to be reviewed.
      RESULTS: Although varied adjuvant modalities have been proved to be benefit for
      treating gastric cancer, surgery is still the most important treatment strategy
      against gastric cancer. Actively adapting to new technology is important but it
      should be balanced with an effort to establish sound scientific rationale that
      adheres to oncologic principles. CONCLUSIONS: Future treatment of gastric cancer
      will be focused on tailored, personalized therapy. For achieving it,
      collaboration across disciplines is essential. Also the philosophy of caring for
      the patients with gastric cancer should be rooted in the realization of true
      patient benefit regardless of who is providing the care. With these philosophies,
      we can shift the scientific and technological advances toward triumph over
      gastric cancer.

PMID- 24451964
TI  - Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with
      metastatic colorectal cancer: a meta-analysis.
AB  - BACKGROUND: What benefits and toxicities patients acquire from the use of
      bevacizumab combined with firstline chemotherapy remains controversial. This
      study was performed to evaluate the efficacy and safety of first-line
      chemotherapy plus bevacizumab in patients with metastatic colorectal cancer
      (mCRC). METHODS: Several databases, including PubMed, Embase, and Cochrane
      Library, were searched up to April 30, 2013. Eligible studies were only
      randomized, controlled trials (RCTs) with a direct comparison between mCRC
      patients treated with and without bevacizumab. Overall risk ratio (RR), hazard
      ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) were calculated
      employing fixed or random-effects models depending on the heterogeneity of the
      included trials. RESULTS: Six RCTs, including 1582 patients in chemotherapy plus
      bevacizumab group and 1484 patients in chemotherapyalone group, were included.
      Overall, the addition of bevacizumab to first-line chemotherapy increased overall
      response rate (ORR) by 4.5%, prolonged both progression-free survival (PFS) and
      overall survival (OS), and increased the rate of total Grades 3 or 4 adverse
      events (G3/4AEs) by 6.9%. Significant differences were found in ORR (RR = 1.22
      (95% CI 1.01-1.46), P = 0.03), PFS (HR = 0.60 (95% CI 0.47-0.77), P < 0.0001), OS
      (HR = 0.83 (95% CI 0.70-0.97), P = 0.02), and any G3/4AEs (OR = 1.56 (95% CI 1.29
      1.89), P < 0.00001). CONCLUSION: Bevacizumab is a valuable addition to the
      current first-line chemotherapy regimens used in patients with mCRC, because of
      conferring a significant improvement in ORR, PFS, and OS, even though it
      increased adverse events.

PMID- 24451966
TI  - MicroRNAs are implicated in the initiation and progression of gastric cancer.
AB  - OBJECTIVE: Gastric cancer is a genetically heterogeneous disease that progresses
      via different oncogenes. MicroRNA (miRNA) can regulate oncogene expression at the
      post-translational level. In this review, we summarize the most commonly altered
      miRNAs and their possible roles in cancer initiation and progression in gastric
      cancer. DATA SOURCES: Most articles were identified by searching PubMed online
      resources using the key terms of microRNA and gastric cancer. STUDY SELECTION:
      Mainly original milestone articles and critical reviews written by major pioneer
      investigators in the field were selected, and the 69 most important articles were
      cited finally. RESULTS: A set of miRNAs are consistently deregulated in gastric
      cancer, although there is no clear miRNA expression profiles, such as miR-21 and
      miR-17 (~92 clusters). These deregulated miRNAs play important roles in promoting
      cell proliferation, tumor metastasis, and chemotherapeutic resistance in gastric
      cancer by targeting different oncogenes. Clinical relevance of these deregulated
      miRNAs is proved to be associated with TNM stages, metastasis, and prognosis of
      gastric cancer patients. In addition, circulating miRNAs are promising
      noninvasive biomarkers for gastric cancer. CONCLUSIONS: miRNAs have produced a
      novel paradigm in research in gastric cancer. These small molecules play
      macroroles in gastric cancer initiation and progression. These results will help
      us improve management of gastric cancer in future.

PMID- 24451968
TI  - Helicobacter pylori infection: an overview in 2013, focus on therapy.
AB  - OBJECTIVE: This article aimed to review the incidence of Helicobacter pylori (H.
      pylori) infection and its therapy. DATA SOURCES: Relevant articles published in
      English were identified by searching in PubMed from 2000 to 2013, with keywords
      "H. pylori". Important references from selected articles were also retrieved from
      Elsevier, Wiley, EBSCO, and SPRINGER. The Chinese articles published were
      searched from China National Knowledge Infrastructure (CNKI). STUDY SELECTION:
      Articles about "prevalence", "gastric carcinoma", "peptic ulcer",
      "gastroesophageal reflux disease", "functional dyspepsia", "pathogenic
      mechanism", "therapy", "eradication rate", "antibiotic resistance", and "gene
      polymorphisms" were selected. RESULTS: The decreased infection rates of H. pylori
      could also be linked to the changed disease spectrum, such as the decreased
      morbidity and recurrence rate of H. pylori-related peptic ulcer, and the
      increased morbidity of gastroesophageal reflux. Although different treatment
      regimens have been used for H. pylori infection, the H. pylori eradication rate
      declined gradually. Due to primary resistance to antibiotics, the gene
      polymorphism of host and infected strain, and the therapy regimes, H. pylori
      eradication became even more difficult. CONCLUSIONS: The prevalence of H. pylori
      infection had been decreasing, but the rate of eradication failure has
      dramatically risen in many countries due to resistance to antibiotic. H. pylori
      therapy in clinical practice is becoming progressively more difficult.

PMID- 24451967
TI  - Lymph node metastasis in early gastric cancer.
AB  - OBJECTIVE: To discuss the clinicopathological factors for lymph node metastasis
      (LNM) in early gastric cancer (EGC), including age, gender, location, size,
      macroscopic type, depth of invasion, histological type, and lymphatic invasion,
      and the regulation of LNM in EGC. DATA SOURCES: The data used in this review were
      mainly from PubMed articles published in English. The search terms were "early
      gastric cancer" and "lymph node metastasis". STUDY SELECTION: Articles were
      selected if they reported the clinicopathological factors and regulation of LNM
      in EGC. RESULTS: The prognosis of EGC is better than advanced gastric cancer,
      with over 90% 5-year survival rate. The main risk factors for LNM in EGC are
      tumor size, macroscopic type, depth of invasion, histological type, ulceration,
      and lymphatic invasion. CONCLUSIONS: LNM in EGC is a critical factor for
      assessment of prognosis and determination of therapeutic strategy. Endoscopic
      mucosal resection or endoscopic submucosal dissection should be considered when
      patients have low risk of LNM.

PMID- 24451969
TI  - Total mesoesophageal esophagectomy.

PMID- 24451970
TI  - Advances in diagnosis and management of chronic heart failure in China: reference
      limits of N-terminal-pro-B-type natriuretic peptide, pharmacal management, and
      community care.

PMID- 24451971
TI  - Incidence and factors influencing postpartum bacterial vaginosis: a controlled
      study.

PMID- 24451972
TI  - Functional magnetic resonace imaging in patients with optic neuritis.

PMID- 24451973
TI  - Late recurrence and metastasis of an appendiceal goblet cell carcinoid 24 years
      after appendectomy.

PMID- 24451974
TI  - Reproductive outcomes after operative laparoscopy of patients with tubal
      infertility with or without hydrosalpinx.

PMID- 24451975
TI  - Emergency scenario of fentanyl induced faciocervical rigidity and complete upper
      airway obstruction during anesthesia induction.

PMID- 24451976
TI  - Laser confocal microscopy findings of Thygeson superficial punctate keratitis.

PMID- 24451977
TI  - Acute graft occlusion caused by heparin resistance during on-pump coronary artery
      bypass graft surgery.

PMID- 24451978
TI  - Tuberculoid leprosy presenting as unilateral big toe drop.

PMID- 24451979
TI  - Structural basis for the active site inhibition mechanism of human kidney-type
      glutaminase (KGA).
AB  - Glutaminase is a metabolic enzyme responsible for glutaminolysis, a process
      harnessed by cancer cells to feed their accelerated growth and proliferation.
      Among the glutaminase isoforms, human kidney-type glutaminase (KGA) is often
      upregulated in cancer and is thus touted as an attractive drug target. Here we
      report the active site inhibition mechanism of KGA through the crystal structure
      of the catalytic domain of KGA (cKGA) in complex with 6-diazo-5-oxo-L-norleucine
      (DON), a substrate analogue of glutamine. DON covalently binds with the active
      site Ser286 and interacts with residues such as Tyr249, Asn335, Glu381, Asn388,
      Tyr414, Tyr466 and Val484. The nucleophilic attack of Ser286 sidechain on DON
      releases the diazo group (N2) from the inhibitor and results in the formation of
      an enzyme-inhibitor complex. Mutational studies confirmed the key role of these
      residues in the activity of KGA. This study will be important in the development
      of KGA active site inhibitors for therapeutic interventions. 

PMID- 24451980
TI  - The role of surveillance cultures in guiding ventilator-associated pneumonia
      therapy.
AB  - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is the most frequent
      cause of death among the nosocomial infections acquired in the ICU. Routine
      surveillance endotracheal aspirate (ETA) cultures in patients on mechanical
      ventilation have been proposed to predict the cause of VAP. Our aim is to review
      the available experience regarding the role of surveillance ETA cultures in
      guiding VAP antimicrobial therapy. RECENT FINDINGS: Microorganisms arrive in the
      lower respiratory tract by aspiration from the oropharynx or gastric reflux,
      extension from a contiguous infection, air contamination or by hematogenous
      seeding. Bacterial colonization of the airway leads to the development of VAP and
      may result from the aspiration of oropharyngeal or gastric secretions. Recent
      studies have suggested that surveillance cultures could provide a rationale for
      prescribing appropriate antibiotics, while waiting for culture results, in up to
      95% of patients in whom VAP is ultimately diagnosed by bronchoalveolar lavage
      fluid culture. However, some authors observed that guiding therapy with those
      routine surveillance cultures leads to unacceptably low coverage of the pathogens
      producing VAP. SUMMARY: This article describes the evidence supporting the use of
      routine ETA cultures to prescribe appropriate initial empirical therapy compared
      with the current practice dictated by guidelines.

PMID- 24451981
TI  - MED18 interaction with distinct transcription factors regulates multiple plant
      functions.
AB  - Mediator is an evolutionarily conserved transcriptional regulatory complex.
      Mechanisms of Mediator function are poorly understood. Here we show that
      Arabidopsis MED18 is a multifunctional protein regulating plant immunity,
      flowering time and responses to hormones through interactions with distinct
      transcription factors. MED18 interacts with YIN YANG1 to suppress disease
      susceptibility genes glutaredoxins GRX480, GRXS13 and thioredoxin TRX-h5.
      Consequently, yy1 and med18 mutants exhibit deregulated expression of these genes
      and enhanced susceptibility to fungal infection. In addition, MED18 interacts
      with ABA INSENSITIVE 4 and SUPPRESSOR OF FRIGIDA4 to regulate abscisic acid
      responses and flowering time, respectively. MED18 associates with the promoter,
      coding and terminator regions of target genes suggesting its function in
      transcription initiation, elongation and termination. Notably, RNA polymerase II
      occupancy and histone H3 lysine tri-methylation of target genes are affected in
      the med18 mutant, reinforcing MED18 function in different mechanisms of
      transcriptional control. Overall, MED18 conveys distinct cues to engender
      transcription underpinning plant responses. 

PMID- 24451982
TI  - Adult glucocorticoid exposure leads to transcriptional and DNA methylation
      changes in nuclear steroid receptors in the hippocampus and kidney of mouse male
      offspring.
AB  - Synthetic glucocorticoids (sGCs) are commonly prescribed for the management of
      inflammatory and endocrine disorders. However, nothing is known regarding the
      effects of sGC on adult germline methylome and whether these effects can be
      transmitted to the next generation. We hypothesized that administration of sGC to
      adult male mice alters DNA methylation in mature sperm and modifies the
      transcription and methylation of steroid receptors in male F1 offspring. Adult
      C57BL/6 males (n = 10/group) were injected on five consecutive days with 1 mg/kg
      sGC (i.e., dexamethasone) or vehicle and euthanized 35 or 60 days after initial
      treatment or bred with control females (60 days postinitial treatment; n =
      5/group). A significant increase in global non-CpG methylation was observed in F0
      sperm 60 days following sGC treatment. In the hippocampus and kidney of Postnatal
      Day 50 (PND50) and PND240 male offspring derived from fathers exposed to sGC,
      significant differences in mineralocorticoid receptor (Nr3c2; Mr), estrogen alpha
      receptor (Nr3a1; Ers1), and glucocorticoid receptor (Nr3c1; Gr) expression were
      observed. Furthermore, significant demethylation in regulatory regions of Mr, Gr,
      and Esr1 was observed in the PND50 kidney derived from fathers exposed to sGC.
      This is the first demonstration that paternal pharmacological exposure to sGC can
      alter the expression and DNA methylation of nuclear steroid receptors in brain
      and somatic tissues of offspring. These findings provide proof of principle that
      adult male exposure to sGC can affect DNA methylation and gene expression in
      offspring, indicating the possibility that adult experiences that evoke increases
      in endogenous glucocorticoid (i.e., stress) might have similar effects. 

PMID- 24451984
TI  - Loss of Sertoli-germ cell adhesion determines the rapid germ cell elimination
      during the seasonal regression of the seminiferous epithelium of the large hairy
      armadillo Chaetophractus villosus.
AB  - The armadillo Chaetophractus villosus is a seasonal breeder whose seminiferous
      epithelium undergoes rapid regression with massive germ cell loss, leaving the
      tubules with only Sertoli cells and spermatogonia. Here, we addressed the
      question of whether this regression entails 1) the disassembly of cell junctions
      (immunolocalization of nectin-3, Cadm1, N-cadherin, and beta-catenin, and
      transmission electron microscopy [TEM]); 2) apoptosis (immunolocalization of
      cytochrome c and caspase 3; TUNEL assay); and 3) the involvement of Sertoli cells
      in germ cell phagocytosis (TEM). We showed a dramatic reduction in the extension
      of vimentin filaments associated with desmosomelike junctions at the interface
      between Sertoli and germ cells, and an increased diffusion of the immunosignals
      of nectin-3, Cadm1, N-cadherin, and beta-catenin. Together, these results suggest
      loss of Sertoli-germ cell adhesion, which in turn might determine postmeiotic
      cell sloughing at the beginning of epithelium regression. Then, loss of Sertoli
      germ cell adhesion triggers cell death. Cytochrome c is released from
      mitochondria, but although postmeiotic cells were negative for late apoptotic
      markers, at advanced regression spermatocytes were positive for all apoptotic
      markers. Transmission electron microscopy analysis showed cytoplasmic engulfment
      of cell debris and lipid droplets within Sertoli cells, a sign of their
      phagocytic activity, which contributes to the elimination of the residual
      meiocytes still present in the latest regression phases. These findings are novel
      and add new players to the mechanisms of seminiferous epithelium regression
      occurring in seasonal breeders, and they introduce the armadillo as an
      interesting model for studying seasonal spermatogenesis. 

PMID- 24451983
TI  - Testicular development in male rats is sensitive to a soy-based diet in the
      neonatal period.
AB  - Approximately 30% of infants in the United States are exposed to high doses of
      isoflavones resulting from soy infant formula consumption. Soybeans contain the
      isoflavones genistin and daidzin, which are hydrolyzed in the gastrointestinal
      tract to their genistein and daidzein aglycones. Both aglycones possess hormonal
      activity and may interfere with male reproductive development. Testosterone,
      which supports male fertility, is mainly produced by testicular Leydig cells. Our
      previous studies indicated that perinatal exposure of male rats to isoflavones
      induced proliferative activity in Leydig cells and increased testosterone
      concentrations into adulthood. However, the relevance of the neonatal period as
      part of the perinatal window of isoflavone exposure remains to be established.
      The present study examined the effects of exposure to isoflavones on male
      offspring of dams maintained on a casein-based control or whole soybean diet in
      the neonatal period, that is, Days 2 to 21 postpartum. The results showed that
      the soybean diet stimulated proliferative activity in developing Leydig cells
      while suppressing their steroidogenic capacity in adulthood. In addition,
      isoflavone exposure decreased production of anti-Mullerian hormone by Sertoli
      cells. Similar to our previous in vitro studies of genistein action in Leydig
      cells, daidzein induced proliferation and interfered with signaling pathways to
      suppress steroidogenic activity. Overall, the data showed that the neonatal
      period is a sensitive window of exposure to isoflavones and support the view that
      both genistein and daidzein are responsible for biological effects associated
      with soy-based diets. 

PMID- 24451985
TI  - Stimulatory Effect of Vascular Endothelial Growth Factor on Proliferation and
      Migration of Porcine Trophectoderm Cells and Their Regulation by the
      Phosphatidylinositol-3-Kinase-AKT and Mitogen-Activated Protein Kinase Cell
      Signaling Pathways.
AB  - Vascular endothelial growth factor (VEGF), a potent stimulator for angiogenesis,
      is likely to regulate implantation by stimulating endometrial angiogenesis and
      vascular permeability. In addition to known angiogenetic effects, VEGF has been
      suggested to participate in development of the early embryo as a mediator of
      fetal-maternal dialogue. Current studies have determined VEGF in terms of its
      role in endometrial vascular events, but VEGF-induced effects on the peri
      implantation conceptus (embryo and extraembryonic membranes) remains unknown. In
      the present study, endometrial VEGF, VEGF receptor-1 (VEGFR-1), and VEGF receptor
      2 (VEGFR-2) mRNAs increased significantly during the peri-implantation period of
      pregnancy as compared to the estrous cycle. Expression of VEGF, VEGFR-1, and
      VEGFR-2 mRNAs was abundant in endometrial luminal and glandular epithelia,
      endothelial blood vessels, and scattered cells in the stroma and conceptus
      trophectoderm. In addition, porcine trophectoderm (pTr) cells treated with VEGF
      exhibited increased abundance of phosphorylated (p)-AKT1, p-ERK1/2, p-p70RSK, p
      RPS6, and p-4EBP1 in a time-dependent manner. The addition of U0126, an inhibitor
      of ERK1/2, inhibited VEGF-induced ERK1/2 phosphorylation, but AKT1
      phosphorylation was not affected. The addition of LY294002, a PI3K inhibitor,
      decreased VEGF-induced phosphorylation of ERK1/2 and AKT1. Furthermore, VEGF
      significantly stimulated proliferation and migration of pTr cells, but these
      effects were blocked by SB203580, U0126, rapamycin, and LY294002, which inhibit
      p38 MAPK, ERK1/2, mTOR, and PI3K, respectively. These results suggest that VEGF
      is critical to successful growth and development of pTr during early pregnancy
      and that VEGF-induced stimulatory effect is coordinately regulated by multiple
      cell signaling pathways, including PI3K-AKT1 and MAPK signaling pathways. 

PMID- 24451986
TI  - Effect of epidermal growth factor-like peptides on the metabolism of in vitro-
      matured mouse oocytes and cumulus cells.
AB  - Oocyte in vitro maturation (IVM) is an assisted reproductive technology that
      involves the maturation of cumulus-oocyte complexes (COCs) that are then capable
      of normal development. We have shown that epidermal growth factor (EGF)-like
      peptide signaling is perturbed in mouse COCs undergoing IVM when matured with
      follicle-stimulating hormone (FSH) and/or EGF, but supplementation of IVM with
      EGF-like peptides amphiregulin or epiregulin improves oocyte developmental
      competence. Here we aimed to determine whether EGF-like peptides regulate COC
      metabolism. Immature 129/Sv mouse COCs underwent IVM with FSH, EGF, amphiregulin,
      epiregulin, betacellulin, or no treatment (control). Epiregulin significantly
      increased intraoocyte flavin adenine dinucleotide (FAD) and REDOX (reduction and
      oxidation) ratio compared to FSH and control. Amphiregulin and epiregulin
      significantly increased the proportion of J aggregates (from JC-1) in oocyte
      mitochondria compared to control, FSH, or EGF, and this coupled with FAD and
      REDOX measures indicates greater mitochondrial activity. There were no
      differences in glucose consumption, lactate production, or glycolysis between
      COCs matured with FSH, EGF, and EGF-like peptides. COCs matured with EGF or EGF
      like peptides exhibited significantly higher mRNA expression of the hexosamine
      biosynthesis pathway (HBP) rate-limiting enzyme gene Gfpt2, Has2 expression, and
      global beta-O-linked glycosylation of proteins, compared to control or FSH,
      suggesting greater HBP activity. Our findings suggest that 1) EGF-like peptides,
      particularly epiregulin, induce more oocyte mitochondrial activity than EGF or
      FSH and 2) EGF-like peptides and EGF induce greater HBP activity, enabling more
      hyaluronic acid synthesis and protein beta-O-linked glycosylation. These
      metabolic alterations may be a mechanism by which EGF-like peptides increase
      oocyte developmental competence. 

PMID- 24451987
TI  - Integral proteomic analysis of blastocysts reveals key molecular machinery
      governing embryonic diapause and reactivation for implantation in mice.
AB  - Among nearly 100 mammalian species, implantation can be suspended at blastocyst
      stage for a certain time and reactivated under favorable conditions, a phenomenon
      known as embryonic diapause. Until now, the underlying molecular mechanism
      governing embryonic diapause and reactivation for implantation remained largely
      unknown. Here we conducted the first integral proteomic analysis of blastocysts
      from diapause to reactivation by using a physiologically relevant mouse delayed
      implantation model. More than 6000 dormant and reactivated blastocysts were used
      for the proteomic analysis. A total of 2255 proteins were detected. Various
      cellular and molecular processes, including protein translation, aerobic
      glycolysis, pentose phosphate pathway, purine nucleotide biosynthesis,
      glutathione metabolism, and chromatin organization were identified as
      differentially regulated. In particular, we demonstrated a remarkable activation
      of mitochondria in blastocysts upon reactivation from dormancy, highlighting
      their essential physiological significance. Moreover, the activities of the
      endosome-lysosome system were prominently enhanced in the mural trophectoderm of
      reactivated blastocysts, accompanied by active phagocytosis at the fetal-maternal
      interface, suggesting a critical role in promoting trophoblast invasion.
      Collectively, we provided an integral proteomic view upon the regulatory network
      of blastocyst reactivation from diapause, which will help to better interpret the
      nature of embryonic diapause and reactivation in wild animals and to identify
      molecular indicators for selecting blastocysts with high implantation competency.

PMID- 24451988
TI  - Pacific white shrimp (Litopenaeus vannamei) vitellogenesis-inhibiting hormone
      (VIH) is predominantly expressed in the brain and negatively regulates
      hepatopancreatic vitellogenin (VTG) gene expression.
AB  - Ovarian maturation in crustaceans is temporally orchestrated by two processes:
      oogenesis and vitellogenesis. The peptide hormone vitellogenesis-inhibiting
      hormone (VIH), by far the most potent negative regulator of crustacean
      reproduction known, critically modulates crustacean ovarian maturation by
      suppressing vitellogenin (VTG) synthesis. In this study, cDNA encoding VIH was
      cloned from the eyestalk of Pacific white shrimp, Litopenaeus vannamei, a highly
      significant commercial culture species. Phylogenetic analysis suggests that L.
      vannamei VIH (lvVIH) can be classified as a member of the type II crustacean
      hyperglycemic hormone family. Northern blot and RT-PCR results reveal that both
      the brain and eyestalk were the major sources for lvVIH mRNA expression. In in
      vitro experiments on primary culture of shrimp hepatopancreatic cells, it was
      confirmed that some endogenous inhibitory factors existed in L. vannamei
      hemolymph, brain, and eyestalk that suppressed hepatopancreatic VTG gene
      expression. Purified recombinant lvVIH protein was effective in inhibiting VTG
      mRNA expression in both in vitro primary hepatopancreatic cell culture and in
      vivo injection experiments. Injection of recombinant VIH could also reverse
      ovarian growth induced by eyestalk ablation. Furthermore, unilateral eyestalk
      ablation reduced the mRNA level of lvVIH in the brain but not in the remaining
      contralateral eyestalk. Our study, as a whole, provides new insights on VIH
      regulation of shrimp reproduction: 1) the brain and eyestalk are both important
      sites of VIH expression and therefore possible coregulators of hepatopancreatic
      VTG mRNA expression and 2) eyestalk ablation could increase hepatopancreatic VTG
      expression by transcriptionally abolishing eyestalk-derived VIH and diminishing
      brain-derived VIH. 

PMID- 24451989
TI  - Expression and regulation of MMP1, MMP3, and MMP9 in the chicken ovary in
      response to gonadotropins, sex hormones, and TGFB1.
AB  - Matrix metalloproteinases (MMPs) are a specific class of proteolytic enzymes that
      play critical roles in follicular development and luteinization in mammals.
      However, the role of MMPs in avian ovary remains largely unknown. We found that
      three MMP genes (MMP1, MMP3, and MMP9) were significantly up-regulated in 23-wk
      old (laying phase) chicken ovaries compared with 6-wk-old ovaries (prepubertal
      phase). In reproductively active chicken ovary, MMP1 expression (both mRNA and
      protein) remained low in prehierarchical and preovulatory follicles but increased
      in postovulatory follicles (POFs). Both MMP3 and MMP9 expression levels increased
      during follicular maturation. MMP3 reached maximal expression in the first
      largest follicle (F1), while MMP9 levels continued to rise in POF1 and POF2 after
      ovulation. Immunohistochemistry, Western blot analysis, and zymography
      experiments indicated that MMP1, MMP3, and MMP9 were synthesized and secreted by
      granulosa cells of different follicles in the chicken ovary. The mRNA expression
      of MMP1 and MMP3 in the granulosa cells was stimulated by follicle-stimulating
      hormone, luteinizing hormone, progesterone, and estrogen but not by transforming
      growth factor beta 1 (TGFB1). However, the mRNA of MMP9 was induced by TGFB1 but
      not follicle-stimulating hormone, luteinizing hormone, progesterone, or estrogen.
      Luciferase reporter and mutagenesis analysis indicated the AP1 and NFkappaB
      elements located in the promoter region from -1700 to -2400 bp were critical for
      both basal and TGFB1-induced MMP9 transcription. These data provide the first
      spatial-temporal expression analysis of MMP system in the chicken ovary. 

PMID- 24451990
TI  - Assessment of rotation thromboelastometry (ROTEM) parameters in patients with
      multiple myeloma at diagnosis.
AB  - INTRODUCTION: Patients with multiple myeloma (MM) have an increased risk of
      thromboembolic events (TEE). Due to the complex nature of the prothrombotic state
      in MM, no single laboratory test has been designed to identify patients with the
      highest risk of developing TEE. Hence, this study is intended to assess the
      feasibility of using global hemostasis test rotation thromboelastometry (ROTEM)
      in MM patients to identify the presence of changes indicating hypercoagulability.
      MATERIALS AND METHODS: The study included 26 patients with MM at the time of
      diagnosis and 20 healthy volunteers. Clotting time (CT), clot formation time
      (CFT), alpha angle (alpha), maximum clot firmness (MCF) and maximum lysis (ML)
      were among the most important parameters recorded during the NATEM, INTEM, EXTEM,
      FIBTEM and APTEM tests. RESULTS: For the NATEM test, CT and CFT readings were
      markedly lower in MM patients than in controls (524s v. 753s; p=0.0006 and 136s
      v. 242s; p=0.02 respectively). However, no marked differences concerning these
      parameters were observed in the INTEM, EXTEM, FIBTEN or APTEM tests. alpha-angle
      values were significantly higher for MM samples according to the NATEM, EXTEM,
      FIBTEM and APTEM tests (64 degrees  v. 48.5 degrees , p=0.02; 77 degrees  v. 74
      degrees , p=0.02; 80 degrees  v.69.5 degrees , p=0.00007; 77 degrees  v. 74
      degrees , p=0.01 respectively). MCF readings were significantly higher in the
      FIBTEM test (22mm v. 15.5mm, p=0.0003) in MM patients. Also, the NATEM test
      revealed a trend toward higher MCF values in MM samples (56mm v. 49.5mm,
      p=0.055). No marked differences were seen in the INTEM, EXTEM and APTEM tests. ML
      readings were markedly lower (0 % v. 4.5 %, p=0.0008) in MM samples than in
      controls according to the FIBTEM test. The studied clot lysis parameters did not
      differ markedly between analyzed groups in other tests. Marked negative
      correlations were noted between IgG concentration and CT (EXTEM, FIBTEM) and CFT
      (INTEM), as well as a significant positive correlation between IgG concentration
      and MCF (INTEM, FIBTEM) and alpha (INTEM) in MM IgG patients. CONCLUSIONS: Our
      results suggest that patients with MM display changes in ROTEM tests at the time
      of diagnosis that may indicate a prothrombotic state.

PMID- 24451991
TI  - Structural basis of redox-dependent modulation of galectin-1 dynamics and
      function.
AB  - Galectin-1 (Gal-1), a member of a family of multifunctional lectins, plays key
      roles in diverse biological processes including cell signaling, immunomodulation,
      neuroprotection and angiogenesis. The presence of an unusual number of six
      cysteine residues within Gal-1 sequence prompted a detailed analysis of the
      impact of the redox environment on the functional activity of this lectin. We
      examined the role of each cysteine residue in the structure and function of Gal-1
      using both experimental and computational approaches. Our results show that: (i)
      only three cysteine residues present in each carbohydrate recognition domain
      (CRD) (Cys2, Cys16 and Cys88) were important in protein oxidation, (ii) oxidation
      promoted the formation of the Cys16-Cys88 disulfide bond, as well as multimers
      through Cys2, (iii) the oxidized protein did not bind to lactose, probably due to
      poor interactions with Arg48 and Glu71, (iv) in vitro oxidation by air was
      completely reversible and (v) oxidation by hydrogen peroxide was relatively slow
      (1.7 +/- 0.2 M(-1) s(-1) at pH 7.4 and 25 degrees C). Finally, an analysis of key
      cysteines in other human galectins is also provided in order to predict their
      behaviour in response to redox variations. Collectively, our data provide new
      insights into the structural basis of Gal-1 redox regulation with critical
      implications in physiology and pathology. 

PMID- 24451993
TI  - The global burden of anxiety disorders in 2010.
AB  - BACKGROUND: Despite their high prevalence, the global burden of anxiety disorders
      has never been calculated comprehensively. The new Global Burden of Disease (GBD)
      study has estimated burden due to morbidity and mortality caused by any anxiety
      disorder. METHOD: Prevalence was estimated using Bayesian meta-regression
      informed by data identified in a systematic review. Years of life lived with
      disability (YLDs) were calculated by multiplying prevalent cases by an average
      disability weight based on severity proportions (mild, moderate and severe).
      Disability-adjusted life years (DALYs) were then calculated and age standardized
      using global standard population figures. Estimates were also made for additional
      suicide mortality attributable to anxiety disorders. Findings are presented for
      YLDs, DALYs and attributable burden due to suicide for 21 world regions in 1990
      and 2010. RESULTS: Anxiety disorders were the sixth leading cause of disability,
      in terms of YLDs, in both high-income (HI) and low- and middle-income (LMI)
      countries. Globally, anxiety disorders accounted for 390 DALYs per 100,000
      persons [95% uncertainty interval (UI) 191-371 DALYs per 100,000] in 2010, with
      no discernible change observed over time. Females accounted for about 65% of the
      DALYs caused by anxiety disorders, with the highest burden in both males and
      females experienced by those aged between 15 and 34 years. Although there was
      regional variation in prevalence, the overlap between uncertainty estimates means
      that substantive differences in burden between populations could not be
      identified. CONCLUSIONS: Anxiety disorders are chronic, disabling conditions that
      are distributed across the globe. Future estimates of burden could be further
      improved by obtaining more representative data on severity state proportions.

PMID- 24451992
TI  - Tribolium embryo morphogenesis: may the force be with you.
AB  - Development of multicellular organisms depends on patterning and growth
      mechanisms encoded in the genome, but also on the physical properties and
      mechanical interactions of the constituent cells that interpret these genetic
      cues. This fundamental biological problem requires integrated studies at multiple
      levels of biological organization: from genes, to cell behaviors, to tissue
      morphogenesis. We have recently combined functional genetics with live imaging
      approaches in embryos of the insect Tribolium castaneum, in order to understand
      their remarkable transformation from a uniform single-layered blastoderm into a
      condensed multi-layered embryo covered by extensive extra-embryonic tissues. We
      first developed a quick and reliable methodology to fluorescently label various
      cell components in entire Tribolium embryos. Live imaging of labeled embryos at
      single cell resolution provided detailed descriptions of cell behaviors and
      tissue movements during normal embryogenesis. We then compared cell and tissue
      dynamics between wild-type and genetically perturbed embryos that exhibited
      altered relative proportions of constituent tissues. This systematic comparison
      led to a qualitative model of the molecular, cellular and tissue interactions
      that orchestrate the observed epithelial rearrangements. We expect this work to
      establish the Tribolium embryo as a powerful and attractive model system for
      biologists and biophysicists interested in the molecular, cellular and mechanical
      control of tissue morphogenesis. 

PMID- 24451994
TI  - Quantitative characterization of nanoscale polycrystalline magnets with electron
      magnetic circular dichroism.
AB  - Electron magnetic circular dichroism (EMCD) allows the quantitative, element
      selective determination of spin and orbital magnetic moments, similar to its well
      established X-ray counterpart, X-ray magnetic circular dichroism (XMCD). As an
      advantage over XMCD, EMCD measurements are made using transmission electron
      microscopes, which are routinely operated at sub-nanometre resolution, thereby
      potentially allowing nanometre magnetic characterization. However, because of the
      low intensity of the EMCD signal, it has not yet been possible to obtain
      quantitative information from EMCD signals at the nanoscale. Here we demonstrate
      a new approach to EMCD measurements that considerably enhances the outreach of
      the technique. The statistical analysis introduced here yields robust
      quantitative EMCD signals. Moreover, we demonstrate that quantitative magnetic
      information can be routinely obtained using electron beams of only a few
      nanometres in diameter without imposing any restriction regarding the crystalline
      order of the specimen. 

PMID- 24451995
TI  - Detection of thalidomide embryotoxicity by in vitro embryotoxicity testing based
      on human iPS cells.
AB  - The mouse embryonic stem cell test (mEST) is used to assess the embryotoxicity of
      drug candidates by evaluating the effects on the cardiac differentiation of stem
      cells. However, thalidomide embryotoxicity has not yet been reported using the
      mEST. To detect the effects of thalidomide, we used human induced pluripotent
      stem cells (hiPSCs) instead of mouse embryonic stem cells, and assessed three
      endpoints: the inhibition of cardiac differentiation, the cytotoxicity to hiPSCs,
      and the cytotoxicity to human dermal fibroblasts, according to the mEST. From
      these data (IC50 values), the embryotoxicity was classified into one of three
      different classes based on the mEST and our criteria. Valproate was used as a
      positive control and ascorbic acid was used as a negative control, and their
      effects were assessed. Similar to valproate, thalidomide was classified as a
      Class 2 agent, with weak embryotoxicity, by the mEST criteria, and was classified
      as Category 3 embryotoxic based on our criteria. Ascorbic acid was classified as
      a Class 1 / Category 1, non-embryotoxic agent, based on both criteria.
      Thalidomide embryotoxicity was detected in the embryonic stem cell test based on
      hiPSCs. This test system is thus considered to have a much greater predictive
      ability than the mEST.

PMID- 24451996
TI  - Effects of pH on nifekalant-induced electrophysiological change assessed in the
      Langendorff heart model of guinea pigs.
AB  - Since information regarding the effects of pH on the extent of nifekalant-induced
      repolarization delay and torsades de pointes remains limited, we assessed it with
      a Langendorff heart model of guinea pigs. First, we investigated the effects of
      pH change from 7.4 to 6.4 on the bipolar electrogram simulating surface lead II
      ECG, monophasic action potential (MAP), effective refractory period (ERP), and
      terminal repolarization period (TRP) and found that acidic condition transiently
      enhanced the ventricular repolarization. Next, we investigated the effects of pH
      change from 6.4 to 7.4 in the presence of nifekalant (10 MUM) on the ECG, MAP,
      ERP, TRP, and short-term variability (STV) of MAP90 and found that the
      normalization of pH prolonged the MAP90 and ERP while the TRP remained unchanged,
      suggesting the increase in electrical vulnerability of the ventricle. Meanwhile,
      the STV of MAP90 was the largest at pH 6.4 in the presence of nifekalant,
      indicating the increase in temporal dispersion of repolarization, which gradually
      decreased with the return of pH to 7.4.Thus, a recovery period from acidosis
      might be more dangerous than during the acidosis, because electrical
      vulnerability may significantly increase for this period while temporal
      dispersion of repolarization remained increased.

PMID- 24451997
TI  - High-performance self-powered UV photodetectors based on TiO2 nano-branched
      arrays.
AB  - Nano-branched TiO2 arrays were fabricated on fluorine-doped tin oxide (FTO) glass
      by a facile two-step chemical synthesis process. Self-powered UV photodetectors
      based on photoelectrochemical cells (PECs) were assembled using these TiO2 nano
      branched arrays as photoanodes. These visible-blind self-powered UV
      photodetectors exhibit high sensitivity and high-speed photoresponse. Compared
      with photodetectors based on bare TiO2 nanorod arrays, TiO2 nano-branched arrays
      show drastically improved photodetecting performance as photoanodes. The
      photosensitivity increases from 0.03 to 0.22 A W(-1) when optimized nano-branched
      TiO2 arrays are used, corresponding to an incident photon-to-current conversion
      efficiency higher than 77%. The UV photodetectors also exhibit excellent spectral
      selectivity and fast response (0.05 s decay time). The improved performance is
      attributed to a markedly enlarged TiO2/electrolyte contact area and good electron
      conductivity in the one-dimensional, well-aligned TiO2 nanorod trunk.

PMID- 24451998
TI  - Differences in Al distribution and acidic properties between RTH-type zeolites
      synthesized with OSDAs and without OSDAs.
AB  - In addition to the original preparation route of the RTH-type zeolites using
      1,2,2,6,6-pentamethylpiperidine (PMP) as an organic structure directing agent
      (OSDA), we have found that simpler organic amines such as N-methylpiperidine and
      pyridine can be used as alternative OSDAs in place of PMP. Furthermore, we have
      established a synthesis method for preparing the RTH-type zeolites without using
      any OSDAs. In this study, RTH-type aluminosilicates were synthesized with
      different types of OSDA or without using any OSDAs. The obtained zeolites
      synthesized with different preparation methods were characterized by using
      various techniques, especially high-resolution (27)Al MAS NMR and in situ FT-IR
      techniques using CO adsorption. The relationship between the preparation method
      and the catalytic performance in the methanol to olefins (MTO) reaction was
      discussed. Finally, the distribution of Al species in the RTH-framework was
      clarified. 

PMID- 24452004
TI  - Solid-state solar modules based on mesoscopic organometal halide perovskite: a
      route towards the up-scaling process.
AB  - We fabricated the first solid state modules based on organometal halide
      perovskite CH3NH3PbI3-xClx using Spiro-OMeTAD and poly(3-hexylthiophene) as hole
      transport materials. Device up-scaling was performed using innovative procedures
      to realize large-area cells and the integrated series-interconnections. The
      perovskite-based modules show a maximum conversion efficiency of 5.1% using both
      poly(3-hexylthiophene) and Spiro-OMeTAD. A long-term stability test was performed
      (in air, under AM1.5G, 1 Sun illumination conditions) using both materials
      showing different behaviour under continuous light stress. Whilst the poly(3
      hexylthiophene)-based module efficiency drops by about 80% with respect to the
      initial value after 170 hours, the Spiro-based module shows a promising long-term
      stability maintaining more than 60% of its initial efficiency after 335 hours. 

PMID- 24451999
TI  - Divergent label-free cell phenotypic pharmacology of ligands at the overexpressed
      beta2-adrenergic receptors.
AB  - We present subclone sensitive cell phenotypic pharmacology of ligands at the
      beta2-adrenergic receptor (beta2-AR) stably expressed in HEK-293 cells. The
      parental cell line was transfected with green fluorescent protein (GFP)-tagged
      beta2-AR. Four stable subclones were established and used to profile a library of
      sixty-nine AR ligands. Dynamic mass redistribution (DMR) profiling resulted in a
      pharmacological activity map suggesting that HEK293 endogenously expresses
      functional Gi-coupled alpha2-AR and Gs-coupled beta2-AR, and the label-free cell
      phenotypic activity of AR ligands are subclone dependent. Pathway deconvolution
      revealed that the DMR of epinephrine is originated mostly from the remodeling of
      actin microfilaments and adhesion complexes, to less extent from the microtubule
      networks and receptor trafficking, and certain agonists displayed different
      efficacy towards the cAMP-Epac pathway. We demonstrate that receptor signaling
      and ligand pharmacology is sensitive to the receptor expression level, and the
      organization of the receptor and its signaling circuitry. 

PMID- 24452005
TI  - Preface of the special issue: "recent CMV research".

PMID- 24452006
TI  - First molecular evidence for Puumala hantavirus in Poland.
AB  - Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with
      renal syndrome (HFRS), and is responsible for the majority of hantavirus
      infections of humans in Fennoscandia, Central and Western Europe. Although there
      are relatively many PUUV sequences available from different European countries,
      little is known about the presence of this virus in Poland. During population
      studies in 2009 a total of 45 bank voles were trapped at three sites in north
      eastern Poland, namely islands on Dejguny and Dobskie Lakes and in a forest near
      Mikolajki. S and M segment-specific RT-PCR assays detected PUUV RNA in three
      animals from the Mikolajki site. The obtained partial S and M segment sequences
      demonstrated the highest similarity to the corresponding segments of a PUUV
      strain from Latvia. Analysis of chest cavity fluid samples by IgG ELISA using a
      yeast-expressed PUUV nucleocapsid protein resulted in the detection of two
      seropositive samples, both being also RT-PCR positive. Interestingly, at the
      trapping site in Mikolajki PUUV-positive bank voles belong to the Carpathian and
      Eastern genetic lineages within this species. In conclusion, we herein present
      the first molecular evidence for PUUV in the rodent reservoir from Poland. 

PMID- 24452008
TI  - Understanding the drug resistance mechanism of hepatitis C virus NS5B to PF
      00868554 due to mutations of the 423 site: a computational study.
AB  - NS5B, a hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) that plays a
      key role in viral replication, is an important target in the discovery of
      antiviral agents. PF-00868554 is a potent non-nucleoside inhibitor (NNI) that
      binds to the Thumb II allosteric pocket of NS5B polymerase and has shown
      significant promise in phase II clinical trials. Unfortunately, several PF
      00868554 resistant mutants have been identified. M423 variants were the most
      common NS5B mutations that occurred after PF-00868554 monotherapy. In this study,
      we used molecular dynamics (MD) simulations, binding free energy calculations and
      free energy decomposition to explore the drug resistance mechanism of HCV to PF
      00868554 resulting from three representative mutations (M423T/V/I) in NS5B
      polymerase. Free energy decomposition analysis reveals that the loss of binding
      affinity mainly comes from the reduction of both van der Waals (DeltaE(vdw)) and
      electrostatic interaction contributions in the gas phase (DeltaE(ele)). Further
      structural analysis indicates that the location of PF-00868554 and the binding
      mode changed due to mutation of the residue at the 423 site of NS5B polymerase
      from methionine to threonine, isoleucine or valine, which further resulted in the
      loss of binding ability of PF-00868554 to NS5B polymerase. The obtained
      computational results will have important value for the rational design of novel
      non-nucleoside inhibitors targeting HCV NS5B polymerase.

PMID- 24452007
TI  - Analysis of essential viral gene functions after highly efficient adenofection of
      cells with cloned human cytomegalovirus genomes.
AB  - Human cytomegalovirus (HCMV) has a large 240 kb genome that may encode more than
      700 gene products with many of them remaining uncharacterized. Mutagenesis of
      bacterial artificial chromosome (BAC)-cloned CMV genomes has greatly facilitated
      the analysis of viral gene functions. However, the roles of essential proteins
      often remain particularly elusive because their investigation requires the
      cumbersome establishment of suitable complementation systems. Here, we show that
      HCMV genomes can be introduced into cells with unprecedented efficiency by
      applying a transfection protocol based on replication-defective, inactivated
      adenovirus particles (adenofection). Upon adenofection of several permissive cell
      types with HCMV genomes carrying mutations in essential genes, transfection rates
      of up to 60% were observed and viral proteins of all kinetic classes were found
      expressed. This enabled further analyses of the transfected cells by standard
      biochemical techniques. Remarkably, HCMV genomes lacking elements essential for
      viral DNA replication, such as the lytic origin of replication, still expressed
      several late proteins. In conclusion, adenofection allows the study of essential
      HCMV genes directly in BAC-transfected cells without the need for sophisticated
      complementation strategies. 

PMID- 24452010
TI  - A hydrophobic residue in position 15 of the rP2X3 receptor slows desensitization
      and reveals properties beneficial for pharmacological analysis and high
      throughput screening.
AB  - The homotrimeric P2X3 subtype, one of the seven members of the ATP-gated P2X
      receptor family, plays a role in sensory neurotransmission, including
      nociception. To overcome the bias resulting from fast desensitization of the P2X3
      receptor in dose-response analyses, a non-desensitizing P2X2-X3 receptor chimera
      has been repeatedly used as a surrogate for the P2X3 receptor for functional
      analysis. Here, we show that only three of the P2X2-specific amino acid residues
      of the P2X2-X3 chimera, (19)P(21)V(22)I, are needed to confer a slowly
      desensitizing phenotype to the P2X3 receptor. The strongest delay in
      desensitization of the P2X3 receptor by a single residue was observed when
      (15)Ser was replaced by Val or another hydrophobic residue. Pharmacologically,
      the S(15)V-rP2X3 mutant behaved similarly to the wt-P2X3 receptor. Analysis of
      the S(15)V-rP2X3 receptor in 1321N1 astrocytoma cells by a common calcium-imaging
      based assay showed 10-fold higher calcium transients relative to those of the wt
      rP2X3 receptor. The S(15)V-rP2X3 cell line enabled reliable analysis of
      antagonistic potencies and correctly reported the mechanism of action of the P2X3
      receptor antagonists A-317491 and TNP-ATP by a calcium-imaging assay. Together,
      these data suggest that the S(15)V-rP2X3 mutant may be suitable not only for
      automated fluorescence-based screening of molecule libraries for identification
      of lead compounds but also for facilitated pharmacological characterization of
      specific P2X3 receptor ligands. We suggest that the mechanism of desensitization
      of the P2X3 receptor may involve the movement of an N-terminal inactivation
      particle, in analogy to the "hinged-lid" or "ball and chain" mechanisms of
      voltage-gated NaV and Shaker KV channels, respectively. 

PMID- 24452011
TI  - The role of DNA methylation in stress-related psychiatric disorders.
AB  - Epigenetic modifications in response to traumatic experience and stress are
      emerging as important factors in the long-term biological trajectories leading to
      stress-related psychiatric disorders, reflecting both environmental influences as
      well as individual genetic predisposition. In particular, recent evidence on DNA
      methylation changes within distinct genes and pathways but also on a genome-wide
      level provides new insights into the pathophysiology of stress related
      psychiatric disorders. This review summarizes current findings and concepts on
      DNA methylation changes in stress-related disorders with a focus on major
      depressive disorder and posttraumatic stress disorder (PTSD). We highlight
      studies of DNA methylation in animals and humans pertinent to these disorders,
      both focusing on candidate loci as well as genome-wide studies. We describe
      molecular mechanisms of how exposure to stress can induce long lasting changes in
      DNA methylation and how these may relate to the pathophysiology of depression and
      PTSD. We discuss data suggesting that DNA methylation, even in peripheral
      tissues, appears to be an informative reflection of environmental exposures on
      the genome and may have potential as a biomarker for the early prevention of
      stress-related disorders.

PMID- 24452012
TI  - Corneal topographic and tomographic analysis of fellow eyes in unilateral
      keratoconus patients using Pentacam.
AB  - PURPOSE: To evaluate topographic and tomographic changes in fellow eyes in
      unilateral keratoconus (KCN) patients by comparing them with normal eyes. DESIGN:
      Retrospective comparative case series. METHODS: Fourteen eyes of 14 patients with
      unilateral KCN and 34 eyes of 34 refractive surgery candidates were divided into
      3 diagnostic groups using a Pentacam rotating Scheimpflug camera: advanced KCN
      eyes of unilateral KCN (KCN group, 14 eyes), normal fellow eyes of unilateral KCN
      (fellow eye group, 14 eyes), and refractive surgery candidates (normal group, 34
      eyes). Topographic and tomographic parameters, which were obtained from Pentacam
      using sagittal curvature, elevation, and corneal thickness maps, were compared
      among the 3 groups. Receiver operating characteristic (ROC) curves were used to
      identify cutoff points in discriminating between fellow and normal eyes. RESULTS:
      Keratometric asymmetry, topometric indices, and elevation differences (maximum -
      minimum) on both the anterior and posterior surfaces were statistically different
      (P < .05). On ROC curve analysis, keratometric asymmetry and topometric index
      were best at discriminating fellow eyes from normal, followed by elevation
      differences (maximum - minimum) on the posterior and anterior cornea surface.
      CONCLUSIONS: Fellow eyes in unilateral KCN showed differences in several
      parameters that were not detectable with the Pentacam detection program, when
      compared with normal. However, each single parameter alone is not sufficient to
      detect early changes; thus, elevation indices as well as indices of anterior
      curvature should be considered together.

PMID- 24452014
TI  - Controlling Na diffusion by rational design of Si-based layered architectures.
AB  - By means of density functional theory, we systematically investigate the
      insertion and diffusion of Na and Li in layered Si materials (polysilane and H
      passivated silicene), in comparison with bulk Si. It is found that Na binding and
      mobility can be significantly facilitated in layered Si structures. In contrast
      to the Si bulk, where Na insertion is energetically unfavorable, Na storage can
      be achieved in polysilane and silicene. The energy barrier for Na diffusion is
      reduced from 1.06 eV in the Si bulk to 0.41 eV in polysilane. The improvements in
      binding energetics and in the activation energy for Na diffusion are attributed
      to the large surface area and available free volume for the large Na cation.
      Based on these results, we suggest that polysilane may be a promising anode
      material for Na-ion and Li-ion batteries with high charge-discharge rates. 

PMID- 24452013
TI  - The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated
      cell proliferation and migration.
AB  - Alternative splicing of pre-messenger RNA (mRNA) is a critical stage of gene
      regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA
      binding protein involved in mammalian development and spermatogenesis, promotes
      inclusion of weak exons through specific recognition of diverse cis-elements. The
      carboxy-terminal proline-rich domain of DAZAP1 interacts with and neutralizes
      general splicing inhibitors, and is sufficient to activate splicing when
      recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk
      (extracellular signal-regulated protein kinase) pathway and this modification is
      essential for the splicing regulatory activity and the nuclear/cytoplasmic
      translocation of DAZAP1. Using mRNA-seq, we identify endogenous splicing events
      regulated by DAZAP1, many of which are involved in maintaining cell growth.
      Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken
      together, these studies reveal a molecular mechanism that integrates splicing
      control into MEK/Erk-regulated cell proliferation. 

PMID- 24452015
TI  - Second-line treatments for dyslipidemia in patients at risk of cardiovascular
      disease.
AB  - Previous studies have shown that approximately 50% patients at risk of
      cardiovascular disease do not achieve lipid management goals. Thus, improvements
      dyslipidemia management are needed. We investigated the clinical choice and
      efficacy of second-line treatments for dyslipidemia in the Japanese clinical
      setting. Using a retrospective cohort design, we collected lipid profile data
      from patients who had been treated with hypolipidemic agents at a stable dosage
      for at least 12 weeks. These patients had then been administered a second-line
      treatment for dyslipidemia because they had not achieved the low-density
      lipoprotein cholesterol (LDL-C) management goals. We included data from 641
      patients in our analysis. The top three choices for second-line treatment were
      adding ezetimibe, switching to strong statins (statin switching), and doubling
      the original statin dosage (statin doubling). Adding ezetimibe, statin switching,
      and statin doubling decreased LDL-C levels by 28.2 +/- 14.5%, 23.2 +/- 24.4%, and
      23.5 +/- 17.2%, respectively. Among these three strategies, adding ezetimibe
      decreased LDL-C levels to the maximum extent. In patients with dysglycemia,
      baseline-adjusted change in hemoglobin A1c (HbA1c) levels decreased slightly in
      the adding-ezetimibe, statin-switching, and statin-doubling groups, but the
      differences were not statistically significant among the groups (-0.10 +/- 0.62%,
      -0.22 +/- 0.54%, and -0.12 +/- 0.52%, p = 0.19). In conclusion, the most common
      second-line treatment options for dyslipidemia were adding ezetimibe, statin
      switching, or statin doubling. Adding ezetimibe resulted in the highest reduction
      in LDL-C levels. These strategies did not increase HbA1c levels when administered
      with conventional diabetes treatment. 

PMID- 24452016
TI  - Fetal cell carcinogenesis of the thyroid: a modified theory based on recent
      evidence.
AB  - Thyroid cancer cells were believed to be generated by multi-step carcinogenesis,
      in which cancer cells are derived from thyrocytes, via multiple incidences of
      damage to their genome, especially in oncogenes or anti-oncogenes that accelerate
      proliferation or foster malignant phenotypes, such as the ability to invade the
      surrounding tissue or metastasize to distant organs, until a new hypothesis,
      fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid
      tumor cells are assumed to be derived from three types of fetal thyroid cell
      which only exist in fetuses or young children, namely, thyroid stem cells (TSCs),
      thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic
      alternations, such as RET/PTC and PAX8-PPARgamma1 rearrangements and a mutation
      in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from
      differentiating. Fetal cell carcinogenesis effectively explains recent molecular
      and clinical evidence regarding thyroid cancer, including thyroid cancer
      initiating cells (TCICs), and it underscores the importance of identifying a stem
      cells and clarifying the molecular mechanism of organ development in cancer
      research. It introduces three important concepts, the reverse approach, stem cell
      crisis and mature and immature cancers. Further, it implies that analysis of a
      small population of cells in a cancer tissue will be a key technique in
      establishing future laboratory tests. In the contrary, mass analysis such as gene
      expression profiling, whole genomic scan, and proteomics analysis may have
      definite limitations since they can only provide information based on many cells.

PMID- 24452017
TI  - Effects of exenatide on metabolic parameters/control in obese Japanese patients
      with type 2 diabetes.
AB  - The effects of exenatide on glycemic control, lipid metabolism, blood pressure,
      and gastrointestinal symptoms were investigated in obese Japanese patients with
      type 2 diabetes mellitus. Twenty-six outpatients were enrolled and administered 5
      MUg of exenatide twice daily. If there was insufficient weight loss and/or
      insufficient improvement in glycemic control, the dose was increased to 10 MUg
      twice daily. Follow-up was continued until the 12th week of administration.
      Hemoglobin A1c, glycoalbumin, fasting plasma glucose, body weight, fasting serum
      C-peptide, serum lipids, blood pressure, and pulse rate were measured before and
      after the observation period. In the initial phase of exenatide therapy, each
      patient received a diary to record gastrointestinal symptoms. During treatment
      with exenatide, hemoglobin A1c decreased significantly and serum C-peptide
      increased significantly. Body weight, low-density lipoprotein cholesterol, and
      systolic blood pressure decreased significantly. Nausea was the most frequent
      gastrointestinal symptom and occurred in 16 patients. Its onset was noted at a
      mean of 1.7 h after injection, the mean duration was 1.1 h, and it continued for
      a mean of 9.3 days after the initiation of administration. Patients with nausea
      showed a significant decrease in hemoglobin Alc, glycoalbumin, or body weight
      compared with those without nausea. These findings suggest that a more marked
      improvement in metabolic parameters by exenatide can be partly dependent on the
      manifestation of gastrointestinal symptoms.

PMID- 24452018
TI  - Acquisition of innate-like microbial reactivity in mucosal tissues during human
      fetal MAIT-cell development.
AB  - Innate-like, evolutionarily conserved MR1-restricted mucosa-associated invariant
      T (MAIT) cells represent a large antimicrobial T-cell subset in humans. Here, we
      investigate the development of these cells in second trimester human fetal
      tissues. MAIT cells are rare and immature in the fetal thymus, spleen and
      mesenteric lymph nodes. In contrast, mature IL-18Ralpha(+) CD8alphaalpha MAIT
      cells are enriched in the fetal small intestine, liver and lung. Independently of
      localization, MAIT cells express CD127 and Ki67 in vivo and readily proliferate
      in response to Escherichia coli in vitro. Maturation is accompanied by the
      gradual post-thymic acquisition of the PLZF transcription factor and the ability
      to produce IFNgamma and IL-22 in response to bacteria in mucosa. Thus, MAIT cells
      acquire innate-like antimicrobial responsiveness in mucosa before exposure to
      environmental microbes and the commensal microflora. Establishment of this arm of
      immunity before birth may help protect the newborn from a range of pathogenic
      microbes. 

PMID- 24452019
TI  - ASPM and mammalian brain evolution: a case study in the difficulty in making
      macroevolutionary inferences about gene-phenotype associations.

PMID- 24452020
TI  - A dynamic global equilibrium in carnivoran diversification over 20 million years.
AB  - The ecological and evolutionary processes leading to present-day biological
      diversity can be inferred by reconstructing the phylogeny of living organisms,
      and then modelling potential processes that could have produced this genealogy. A
      more direct approach is to estimate past processes from the fossil record. The
      Carnivora (Mammalia) has both substantial extant species richness and a rich
      fossil record. We compiled species-level data for over 10 000 fossil occurrences
      of nearly 1400 carnivoran species. Using this compilation, we estimated
      extinction, speciation and net diversification for carnivorans through the
      Neogene (22-2 Ma), while simultaneously modelling sampling probability. Our
      analyses show that caniforms (dogs, bears and relatives) have higher speciation
      and extinction rates than feliforms (cats, hyenas and relatives), but lower rates
      of net diversification. We also find that despite continual species turnover, net
      carnivoran diversification through the Neogene is surprisingly stable, suggesting
      a saturated adaptive zone, despite restructuring of the physical environment.
      This result is strikingly different from analyses of carnivoran diversification
      estimated from extant species alone. Two intervals show elevated diversification
      rates (13-12 Ma and 4-3 Ma), although the precise causal factors behind the two
      peaks in carnivoran diversification remain open questions. 

PMID- 24452021
TI  - Population-level effects of suppressing fever.
AB  - Fever is commonly attenuated with antipyretic medication as a means to treat
      unpleasant symptoms of infectious diseases. We highlight a potentially important
      negative effect of fever suppression that becomes evident at the population
      level: reducing fever may increase transmission of associated infections. A
      higher transmission rate implies that a larger proportion of the population will
      be infected, so widespread antipyretic drug use is likely to lead to more illness
      and death than would be expected in a population that was not exposed to
      antipyretic pharmacotherapies. We assembled the published data available for
      estimating the magnitudes of these individual effects for seasonal influenza.
      While the data are incomplete and heterogeneous, they suggest that, overall,
      fever suppression increases the expected number of influenza cases and deaths in
      the US: for pandemic influenza with reproduction number , the estimated increase
      is 1% (95% CI: 0.0-2.7%), whereas for seasonal influenza with , the estimated
      increase is 5% (95% CI: 0.2-12.1%). 

PMID- 24452022
TI  - Between migration load and evolutionary rescue: dispersal, adaptation and the
      response of spatially structured populations to environmental change.
AB  - The evolutionary potential of populations is mainly determined by population size
      and available genetic variance. However, the adaptability of spatially structured
      populations may also be affected by dispersal: positively by spreading beneficial
      mutations across sub-populations, but negatively by moving locally adapted
      alleles between demes. We develop an individual-based, two-patch, allelic model
      to investigate the balance between these opposing effects on a population's
      evolutionary response to rapid climate change. Individual fitness is controlled
      by two polygenic traits coding for local adaptation either to the environment or
      to climate. Under conditions of selection that favour the evolution of a
      generalist phenotype (i.e. weak divergent selection between patches) dispersal
      has an overall positive effect on the persistence of the population. However,
      when selection favours locally adapted specialists, the beneficial effects of
      dispersal outweigh the associated increase in maladaptation for a narrow range of
      parameter space only (intermediate selection strength and low linkage among
      loci), where the spread of beneficial climate alleles is not strongly hampered by
      selection against non-specialists. Given that local selection across
      heterogeneous and fragmented landscapes is common, the complex effect of
      dispersal that we describe will play an important role in determining the
      evolutionary dynamics of many species under rapidly changing climate. 

PMID- 24452023
TI  - Prospecting and dispersal: their eco-evolutionary dynamics and implications for
      population patterns.
AB  - Dispersal is not a blind process, and evidence is accumulating that individual
      dispersal strategies are informed in most, if not all, organisms. The acquisition
      and use of information are traits that may evolve across space and time as a
      function of the balance between costs and benefits of informed dispersal. If
      information is available, individuals can potentially use it in making better
      decisions, thereby increasing their fitness. However, prospecting for and using
      information probably entail costs that may constrain the evolution of informed
      dispersal, potentially with population-level consequences. By using individual
      based, spatially explicit simulations, we detected clear coevolutionary dynamics
      between prospecting and dispersal movement strategies that differed in sign and
      magnitude depending on their respective costs. More specifically, we found that
      informed dispersal strategies evolve when the costs of information acquisition
      during prospecting are low but only if there are mortality costs associated with
      dispersal movements. That is, selection favours informed dispersal strategies
      when the acquisition and use processes themselves were not too expensive. When
      non-informed dispersal strategies evolve, they do so jointly with the evolution
      of long dispersal distance because this maximizes the sampling area. In some
      cases, selection produces dispersal rules different from those that would be
      'optimal' (i.e. the best possible population performance--in our context
      quantitatively measured as population density and patch occupancy--among all
      possible individual movement rules) for the population. That is, on the one hand,
      informed dispersal strategies led to population performance below its highest
      possible level. On the other hand, un- and poorly informed individuals nearly
      optimized population performance, both in terms of density and patch occupancy.

PMID- 24452024
TI  - A well-constrained estimate for the timing of the salmonid whole genome
      duplication reveals major decoupling from species diversification.
AB  - Whole genome duplication (WGD) is often considered to be mechanistically
      associated with species diversification. Such ideas have been anecdotally
      attached to a WGD at the stem of the salmonid fish family, but remain untested.
      Here, we characterized an extensive set of gene paralogues retained from the
      salmonid WGD, in species covering the major lineages (subfamilies Salmoninae,
      Thymallinae and Coregoninae). By combining the data in calibrated relaxed
      molecular clock analyses, we provide the first well-constrained and direct
      estimate for the timing of the salmonid WGD. Our results suggest that the event
      occurred no later in time than 88 Ma and that 40-50 Myr passed subsequently until
      the subfamilies diverged. We also recovered a Thymallinae-Coregoninae sister
      relationship with maximal support. Comparative phylogenetic tests demonstrated
      that salmonid diversification patterns are closely allied in time with the
      continuous climatic cooling that followed the Eocene-Oligocene transition, with
      the highest diversification rates coinciding with recent ice ages. Further tests
      revealed considerably higher speciation rates in lineages that evolved anadromy-
      the physiological capacity to migrate between fresh and seawater--than in sister
      groups that retained the ancestral state of freshwater residency. Anadromy, which
      probably evolved in response to climatic cooling, is an established catalyst of
      genetic isolation, particularly during environmental perturbations (for example,
      glaciation cycles). We thus conclude that climate-linked ecophysiological
      factors, rather than WGD, were the primary drivers of salmonid diversification.

PMID- 24452025
TI  - The geography and ecology of plant speciation: range overlap and niche divergence
      in sister species.
AB  - A goal of evolutionary biology is to understand the roles of geography and
      ecology in speciation. The recent shared ancestry of sister species can leave a
      major imprint on their geographical and ecological attributes, possibly revealing
      processes involved in speciation. We examined how ecological similarity, range
      overlap and range asymmetry are related to time since divergence of 71 sister
      species pairs in the California Floristic Province (CFP). We found that plants
      exhibit strikingly different age-range correlation patterns from those found for
      animals; the latter broadly support allopatric speciation as the primary mode of
      speciation. By contrast, plant sisters in the CFP were sympatric in 80% of cases
      and range sizes of sisters differed by a mean of 10-fold. Range overlap and range
      asymmetry were greatest in younger sisters. These results suggest that speciation
      mechanisms broadly grouped under 'budding' speciation, in which a larger ranged
      progenitor gives rise to a smaller ranged derivative species, are probably
      common. The ecological and reproductive similarity of sisters was significantly
      greater than that of sister-non-sister congeners for every trait assessed.
      However, shifts in at least one trait were present in 93% of the sister pairs;
      habitat and soil shifts were especially common. Ecological divergence did not
      increase with range overlap contrary to expectations under character displacement
      in sympatry. Our results suggest that vicariant speciation is more ubiquitous in
      animals than plants, perhaps owing to the sensitivity of plants to fine-scale
      environmental heterogeneity. Despite high levels of range overlap, ecological
      shifts in the process of budding speciation may result in low rates of fine-scale
      spatial co-occurrence. These results have implications for ecological studies of
      trait evolution and community assembly; despite high levels of sympatry, sister
      taxa and potentially other close relatives, may be missing from local
      communities. 

PMID- 24452026
TI  - A Silurian short-great-appendage arthropod.
AB  - A new arthropod, Enalikter aphson gen. et sp. nov., is described from the
      Silurian (Wenlock Series) Herefordshire Lagerstatte of the UK. It belongs to the
      Megacheira (=short-great-appendage group), which is recognized here, for the
      first time, in strata younger than mid-Cambrian age. Discovery of this new
      Silurian taxon allows us to identify a Devonian megacheiran representative,
      Bundenbachiellus giganteus from the Hunsruck Slate of Germany. The phylogenetic
      position of megacheirans is controversial: they have been interpreted as stem
      chelicerates, or stem euarthropods, but when Enalikter and Bundenbachiellus are
      added to the most comprehensive morphological database available, a stem
      euarthropod position is supported. Enalikter represents the only fully three
      dimensionally preserved stem-group euarthropod, it falls in the sister clade to
      the crown-group euarthropods, and it provides new insights surrounding the origin
      and early evolution of the euarthropods. Recognition of Enalikter and
      Bundenbachiellus as megacheirans indicates that this major arthropod group
      survived for nearly 100 Myr beyond the mid-Cambrian. 

PMID- 24452027
TI  - Fish species introductions provide novel insights into the patterns and drivers
      of phylogenetic structure in freshwaters.
AB  - Despite long-standing interest of terrestrial ecologists, freshwater ecosystems
      are a fertile, yet unappreciated, testing ground for applying community
      phylogenetics to uncover mechanisms of species assembly. We quantify phylogenetic
      clustering and overdispersion of native and non-native fishes of a large river
      basin in the American Southwest to test for the mechanisms (environmental
      filtering versus competitive exclusion) and spatial scales influencing community
      structure. Contrary to expectations, non-native species were phylogenetically
      clustered and related to natural environmental conditions, whereas native species
      were not phylogenetically structured, likely reflecting human-related changes to
      the basin. The species that are most invasive (in terms of ecological impacts)
      tended to be the most phylogenetically divergent from natives across watersheds,
      but not within watersheds, supporting the hypothesis that Darwin's naturalization
      conundrum is driven by the spatial scale. Phylogenetic distinctiveness may
      facilitate non-native establishment at regional scales, but environmental
      filtering restricts local membership to closely related species with
      physiological tolerances for current environments. By contrast, native species
      may have been phylogenetically clustered in historical times, but species loss
      from contemporary populations by anthropogenic activities has likely shaped the
      phylogenetic signal. Our study implies that fundamental mechanisms of community
      assembly have changed, with fundamental consequences for the biogeography of both
      native and non-native species. 

PMID- 24452028
TI  - A syndrome of mutualism reinforces the lifestyle of a sloth.
AB  - Arboreal herbivory is rare among mammals. The few species with this lifestyle
      possess unique adaptions to overcome size-related constraints on nutritional
      energetics. Sloths are folivores that spend most of their time resting or eating
      in the forest canopy. A three-toed sloth will, however, descend its tree weekly
      to defecate, which is risky, energetically costly and, until now, inexplicable.
      We hypothesized that this behaviour sustains an ecosystem in the fur of sloths,
      which confers cryptic nutritional benefits to sloths. We found that the more
      specialized three-toed sloths harboured more phoretic moths, greater
      concentrations of inorganic nitrogen and higher algal biomass than the generalist
      two-toed sloths. Moth density was positively related to inorganic nitrogen
      concentration and algal biomass in the fur. We discovered that sloths consumed
      algae from their fur, which was highly digestible and lipid-rich. By descending a
      tree to defecate, sloths transport moths to their oviposition sites in sloth
      dung, which facilitates moth colonization of sloth fur. Moths are portals for
      nutrients, increasing nitrogen levels in sloth fur, which fuels algal growth.
      Sloths consume these algae-gardens, presumably to augment their limited diet.
      These linked mutualisms between moths, sloths and algae appear to aid the sloth
      in overcoming a highly constrained lifestyle. 

PMID- 24452029
TI  - Ocean warming and acidification have complex interactive effects on the dynamics
      of a marine fungal disease.
AB  - Diseases threaten the structure and function of marine ecosystems and are
      contributing to the global decline of coral reefs. We currently lack an
      understanding of how climate change stressors, such as ocean acidification (OA)
      and warming, may simultaneously affect coral reef disease dynamics, particularly
      diseases threatening key reef-building organisms, for example crustose coralline
      algae (CCA). Here, we use coralline fungal disease (CFD), a previously described
      CCA disease from the Pacific, to examine these simultaneous effects using both
      field observations and experimental manipulations. We identify the associated
      fungus as belonging to the subphylum Ustilaginomycetes and show linear lesion
      expansion rates on individual hosts can reach 6.5 mm per day. Further, we
      demonstrate for the first time, to our knowledge, that ocean-warming events could
      increase the frequency of CFD outbreaks on coral reefs, but that OA-induced
      lowering of pH may ameliorate outbreaks by slowing lesion expansion rates on
      individual hosts. Lowered pH may still reduce overall host survivorship, however,
      by reducing calcification and facilitating fungal bio-erosion. Such complex,
      interactive effects between simultaneous extrinsic environmental stressors on
      disease dynamics are important to consider if we are to accurately predict the
      response of coral reef communities to future climate change. 

PMID- 24452030
TI  - Oestradiol and prostaglandin F2alpha regulate sexual displays in females of a sex
      role reversed fish.
AB  - The mechanisms regulating sexual behaviours in female vertebrates are still
      poorly understood, mainly because in most species sexual displays in females are
      more subtle and less frequent than displays in males. In a sex-role reversed
      population of a teleost fish, the peacock blenny Salaria pavo, an external
      fertilizer, females are the courting sex and their sexual displays are
      conspicuous and unambiguous. We took advantage of this to investigate the role of
      ovarian-synthesized hormones in the induction of sexual displays in females. In
      particular, the effects of the sex steroids oestradiol (E2) and testosterone (T)
      and of the prostaglandin F2alpha (PGF2alpha) were tested. Females were
      ovariectomized and their sexual behaviour tested 7 days (sex steroids and
      PGF2alpha) and 14 days (sex steroids) after ovariectomy by presenting females to
      an established nesting male. Ovariectomy reduced the expression of sexual
      behaviours, although a significant proportion of females still courted the male
      14 days after the ovary removal. Administration of PGF2alpha to ovariectomized
      females recovered the frequency of approaches to the male's nest and of courtship
      displays towards the nesting male. However, E2 also had a positive effect on
      sexual behaviour, particularly on the frequency of approaches to the male's nest.
      T administration failed to recover sexual behaviours in ovariectomized females.
      These results suggest that the increase in E2 levels postulated to occur during
      the breeding season facilitates female mate-searching and assessment behaviours,
      whereas PGF2alpha acts as a short-latency endogenous signal informing the brain
      that oocytes are mature and ready to be spawned. In the light of these results,
      the classical view for female fishes, that sex steroids maintain sexual behaviour
      in internal fertilizers and that prostaglandins activate spawning behaviours in
      external fertilizers, needs to be reviewed. 

PMID- 24452031
TI  - Honeybees (Apis mellifera) learn to discriminate the smell of organic compounds
      from their respective deuterated isotopomers.
AB  - The understanding of physiological and molecular processes underlying the sense
      of smell has made considerable progress during the past three decades, revealing
      the cascade of molecular steps that lead to the activation of olfactory receptor
      (OR) neurons. However, the mode of primary interaction of odorant molecules with
      the OR proteins within the sensory cells is still enigmatic. Two different
      concepts try to explain these interactions: the 'odotope hypothesis' suggests
      that OR proteins recognize structural aspects of the odorant molecule, whereas
      the 'vibration hypothesis' proposes that intra-molecular vibrations are the basis
      for the recognition of the odorant by the receptor protein. The vibration
      hypothesis predicts that OR proteins should be able to discriminate compounds
      containing deuterium from their common counterparts which contain hydrogen
      instead of deuterium. This study tests this prediction in honeybees (Apis
      mellifera) using the proboscis extension reflex learning in a differential
      conditioning paradigm. Rewarding one odour (e.g. a deuterated compound) with
      sucrose and not rewarding the respective analogue (e.g. hydrogen-based odorant)
      shows that honeybees readily learn to discriminate hydrogen-based odorants from
      their deuterated counterparts and supports the idea that intra-molecular
      vibrations may contribute to odour discrimination. 

PMID- 24452032
TI  - Spatial scale and sampling resolution affect measures of gap disturbance in a
      lowland tropical forest: implications for understanding forest regeneration and
      carbon storage.
AB  - Treefall gaps play an important role in tropical forest dynamics and in
      determining above-ground biomass (AGB). However, our understanding of gap
      disturbance regimes is largely based either on surveys of forest plots that are
      small relative to spatial variation in gap disturbance, or on satellite imagery,
      which cannot accurately detect small gaps. We used high-resolution light
      detection and ranging data from a 1500 ha forest in Panama to: (i) determine how
      gap disturbance parameters are influenced by study area size, and the criteria
      used to define gaps; and (ii) to evaluate how accurately previous ground-based
      canopy height sampling can determine the size and location of gaps. We found that
      plot-scale disturbance parameters frequently differed significantly from those
      measured at the landscape-level, and that canopy height thresholds used to define
      gaps strongly influenced the gap-size distribution, an important metric
      influencing AGB. Furthermore, simulated ground surveys of canopy height
      frequently misrepresented the true location of gaps, which may affect conclusions
      about how relatively small canopy gaps affect successional processes and
      contribute to the maintenance of diversity. Across site comparisons need to
      consider how gap definition, scale and spatial resolution affect
      characterizations of gap disturbance, and its inferred importance for carbon
      storage and community composition. 

PMID- 24452033
TI  - Do angiotensin type 2 receptors modulate haemodynamic effects of type 1 receptors
      in conscious newborn lambs?
AB  - INTRODUCTION AND HYPOTHESIS: It was hypothesized that in the immediate newborn
      period, when the renin-angiotensin system (RAS) is activated, angiotensin type 2
      receptors (AT2Rs) buffer the haemodynamic effects of angiotensin type 1 receptors
      (AT1Rs), as occurs in adult animals when the RAS is activated. MATERIALS AND
      METHODS: Arterial (systolic, diastolic, and mean) pressures (SAP, DAP, MAP), mean
      venous pressures (MVP) and renal blood flows (RBF) were measured in conscious,
      chronically instrumented lambs aged ~1 (8+/-2 days, N=8) and 6 weeks (41+/-4
      days, N=11). In each animal, measurements were made before and after
      administration of the selective AT1R antagonist ZD 7155 (experiment one) and the
      selective AT2R antagonist PD123319 (experiment two) as well as both antagonists,
      ZD 7155 and PD 123319 (experiment three). RESULTS: Haemodynamic responses to
      combined inhibition of both AT1Rs and AT2Rs were similar to inhibition of AT1Rs
      alone: there was a significant decrease in SAP, DAP, and MAP and a significant
      increase in RBF within minutes of concomitant administration of ZD 7155 and PD
      123319 in both age groups. These responses were similar to responses to ZD 7155
      alone, whereas PD 123319 alone did not alter any of the measured variables.
      CONCLUSIONS: AT2Rs do not counterbalance the pressor and renal vasoconstrictor
      effects elicited by activation of AT1Rs in the immediate newborn period. During
      this time, AT1Rs appear to predominate in eliciting the haemodynamic effects of
      angiotensin II (ANG II), whereas the role of the upregulated AT2Rs remains
      elusive.

PMID- 24452034
TI  - Novel variants detected in AGT gene among patients with essential hypertension.
AB  - INTRODUCTION: AGT is the first gene to be linked to essential hypertension (EHT).
      It harbors several variants of which only few polymorphisms are found to exhibit
      positive and negative associations with hypertension. In the present study, the
      AGT gene was screened to detect already reported and novel variations
      contributing to the development of hypertension. METHOD: In total, 215
      hypertensives and 230 normotensives were screened for variations in all the five
      exons and a part of promoter of AGT gene using single strand conformation
      polymorphism analysis followed by sequencing of samples showing mobility shifts
      on polyacrylamide gels. RESULTS: Five novel variants, namely c.-61G>A in
      promoter, c.-4+17C>T in intron1, c.24T>C and c.28A>T in Exon2, and c.*90 T>C in
      3' untranslated region were detected in the AGT gene. c.-61G>A lies in the
      promoter region that plays a critical role in its expression. Variation c.
      4+17C>T created a new enhancer site. c.24T>C (TCT-TCC) is a silent mutation while
      c.28A>T (p. M10L) has a possible damaging effect on the AGT protein. c.*90T>C,
      detected in the 3' untranslated region is thought to play an important role in
      the translation and stability of the mRNA. CONCLUSION: Studies on the functional
      role of these novel variants are warranted to understand the mechanism underlying
      the development of EHT.

PMID- 24452035
TI  - ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective
      effect of renin-angiotensin system blockade in patients with IgA nephropathy.
AB  - INTRODUCTION: Little is known about genetic predictors that modify the
      renoprotective effect of renin-angiotensin system (RAS) blockade in IgA
      nephropathy (IgAN). MATERIALS AND METHODS: The present multicenter retrospective
      observational study examined effect modification between RAS blockade and three
      RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D
      (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). RESULTS: During 9.9 +/-
      4.2 years of observation, 63 patients progressed to a 50% increase in serum
      creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard
      ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective
      effect of RAS blockade (p for interaction between ACE DD and RAS blockade =
      0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II
      patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade
      1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS
      blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of
      slope of estimated glomerular filtration rate (p = 0.045 for interaction).
      CONCLUSION: ACE I/D predicted the IgAN progression and the renoprotective effect
      of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did.

PMID- 24452036
TI  - Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus:
      Susceptibility and complications.
AB  - HYPOTHESIS/INTRODUCTION: Polymorphisms of angiotensin converting enzyme (ACE) and
      methylene-tetrahydrofolate reductase (MTHFR) genes have been proposed to be
      associated with type 2 diabetes mellitus (T2DM) with conflicting results. This
      work was planned in order to check for the association of these polymorphisms
      with the susceptibility for and complications of T2DM among Egyptian cases.
      MATERIALS AND METHODS: This is a case controlled study involving 203 patients
      with T2DM and 311 healthy controls. Polymorphic variants of ACE I>D and MTHFR
      (677 C>T and 1298 A>C) were determined using the polymerase chain reaction (PCR)
      restriction analysis technique. RESULTS: The susceptibility to T2DM was higher
      among subjects having the MTHFR 677TT (odds ratio (OR)=2.2, p=0.01), MTHFR 1298
      AA (OR=1.84, p=0.001) and ACE (ID+II) (OR=2.0, p=0.0007) genotypes. Logistic
      regression analysis showed that MTHFR 677T allele was a risk factor for diabetic
      retinopathy (DR) (OR=3.47, p<0.001), diabetic polyneuropathy (DPN) (OR=5.2,
      p<0.0001) and ischemic heart disease (IHD) (OR=2.9, p<0.05), while MTHFR 1298 C
      allele was a risk factor for DR (OR=4.2, p<0.001) and the ACE DD genotype was a
      risk factor for DPN (OR=3.1, p<0.001). CONCLUSIONS: The MTHFR 677 TT genotype was
      associated with T2DM susceptibility and complications (DR, DPN and IHD). The
      MTHFR 1298 CC, AC and ACE DD genotypes were associated with DR and DPN.

PMID- 24452037
TI  - Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy
      subjects and gastroesophageal reflux disease patients.
AB  - INTRODUCTION: The human esophageal mucosa expresses various components of the
      renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II
      (AngII). The aim of this study was to investigate the esophageal presence of
      angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV
      receptor (AT4R). The aim was also to study the actions of AngIV and to look for
      aberrations in patients with gastroesophageal reflux disease (GERD). MATERIALS
      AND METHODS: Esophageal biopsies were collected from healthy volunteers (n: 19)
      and individuals with erosive reflux disease (n: 14). Gene transcripts and protein
      expression of aminopeptidase A, -B and -M, and the AT4R were investigated by
      reverse transcriptase polymerase chain reaction (rt-PCR), western blot (WB) and
      immunohistochemistry (IHC). The functional impact of AngIV was examined in an
      Ussing chamber. RESULTS: Aminopeptidase A, -B and -M and the AT4R were expressed
      in the esophageal epithelium. The AT4R was less prominent in certain areas in the
      mucosa of reflux patients. AngIV influenced the esophageal epithelial ion
      transport. The impact was lower in patients with GERD. CONCLUSION: The AT4R and
      formation enzymes of AngIII and AngIV are present in the human esophageal
      epithelium. Moreover, the present results suggest that AngIV exert regulatory
      impact on the epithelium and that RAS is involved in mucosal aberrations
      associated with GERD.

PMID- 24452038
TI  - Health in the Arab world: a renewed opportunity.

PMID- 24452039
TI  - Responding to priority health challenges in the Arab world.

PMID- 24452040
TI  - Health equity in the Arab world: the future we want.

PMID- 24452041
TI  - Huda Zurayk: advancing health and research in the Arab world.

PMID- 24452042
TI  - The state of health in the Arab world, 1990-2010: an analysis of the burden of
      diseases, injuries, and risk factors.
AB  - BACKGROUND: The Arab world has a set of historical, geopolitical, social,
      cultural, and economic characteristics and has been involved in several wars that
      have affected the burden of disease. Moreover, financial and human resources vary
      widely across the region. We aimed to examine the burden of diseases and injuries
      in the Arab world for 1990, 2005, and 2010 using data from the Global Burden of
      Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010). METHODS: We divided
      the 22 countries of the Arab League into three categories according to their
      gross national income: low-income countries (LICs; Comoros, Djibouti, Mauritania,
      Yemen, and Somalia), middle-income countries (MICs; Algeria, Egypt, Iraq, Jordan,
      Lebanon, Libya, Morocco, occupied Palestinian territory, Sudan, Syria, and
      Tunisia), and high-income countries (HICs; Bahrain, Kuwait, Oman, Qatar, Saudi
      Arabia, and the United Arab Emirates). For the whole Arab world, each income
      group, and each individual country, we estimated causes of death, disability
      adjusted life years (DALYs), DALY-attributable risk factors, years of life lived
      with disability (YLDs), years of life lost due to premature mortality (YLLs), and
      life expectancy by age and sex for 1990, 2005, and 2010. FINDINGS: Ischaemic
      heart disease was the top cause of death in the Arab world in 2010 (contributing
      to 14.3% of deaths), replacing lower respiratory infections, which were the
      leading cause of death in 1990 (11.0%). Lower respiratory infections contributed
      to the highest proportion of DALYs overall (6.0%), and in female indivduals
      (6.1%), but ischaemic heart disease was the leading cause of DALYs in male
      individuals (6.0%). DALYs from non-communicable diseases--especially ischaemic
      heart disease, mental disorders such as depression and anxiety, musculoskeletal
      disorders including low back pain and neck pain, diabetes, and cirrhosis-
      increased since 1990. Major depressive disorder was ranked first as a cause of
      YLDs in 1990, 2005, and 2010, and lower respiratory infections remained the
      leading cause of YLLs in 2010 (9.2%). The burden from HIV/AIDS also increased
      substantially, specifically in LICs and MICs, and road injuries continued to rank
      highly as a cause of death and DALYs, especially in HICs. Deaths due to
      suboptimal breastfeeding declined from sixth place in 1990 to tenth place in
      2010, and childhood underweight declined from fifth to 11th place.
      INTERPRETATION: Since 1990, premature death and disability caused by
      communicable, newborn, nutritional, and maternal disorders (with the exception of
      HIV/AIDS) has decreased in the Arab world--although these disorders do still
      persist in LICs--whereas the burden of non-communicable diseases and injuries has
      increased. The changes in the burden of disease will challenge already stretched
      human and financial resources because many Arab countries are now dealing with
      both non-communicable and infectious diseases. A road map for health in the Arab
      world is urgently needed. FUNDING: Bill & Melinda Gates Foundation.

PMID- 24452043
TI  - Governance and health in the Arab world.
AB  - Since late 2010, the Arab world has entered a tumultuous period of change, with
      populations demanding more inclusive and accountable government. The region is
      characterised by weak political institutions, which exclude large proportions of
      their populations from political representation and government services. Building
      on work in political science and economics, we assess the extent to which the
      quality of governance, or the extent of electoral democracy, relates to adult,
      infant, and maternal mortality, and to the perceived accessibility and
      improvement of health services. We compiled a dataset from the World Bank, WHO,
      Institute for Health Metrics and Evaluation, Arab Barometer Survey, and other
      sources to measure changes in demographics, health status, and governance in the
      Arab World from 1980 to 2010. We suggest an association between more effective
      government and average reductions in mortality in this period; however, there
      does not seem to be any relation between the extent of democracy and mortality
      reductions. The movements for changing governance in the region threaten access
      to services in the short term, forcing migration and increasing the vulnerability
      of some populations. In view of the patterns observed in the available data, and
      the published literature, we suggest that efforts to improve government
      effectiveness and to reduce corruption are more plausibly linked to population
      health improvements than are efforts to democratise. However, these patterns are
      based on restricted mortality data, leaving out subjective health metrics,
      quality of life, and disease-specific data. To better guide efforts to transform
      political and economic institutions, more data are needed for health-care access,
      health-care quality, health status, and access to services of marginalised
      groups. 

PMID- 24452044
TI  - Non-communicable diseases in the Arab world.
AB  - According to the results of the Global Burden of Disease Study 2010, the burden
      of non-communicable diseases (cardiovascular disease, cancer, chronic lung
      diseases, and diabetes) in the Arab world has increased, with variations between
      countries of different income levels. Behavioural risk factors, including tobacco
      use, unhealthy diets, and physical inactivity are prevalent, and obesity in
      adults and children has reached an alarming level. Despite epidemiological
      evidence, the policy response to non-communicable diseases has been weak. So far,
      Arab governments have not placed a sufficiently high priority on addressing the
      high prevalence of non-communicable diseases, with variations in policies between
      countries and overall weak implementation. Cost-effective and evidence-based
      prevention and treatment interventions have already been identified. The
      implementation of these interventions, beginning with immediate action on salt
      reduction and stricter implementation of tobacco control measures, will address
      the rise in major risk factors. Implementation of an effective response to the
      non-communicable-disease crisis will need political commitment, multisectoral
      action, strengthened health systems, and continuous monitoring and assessment of
      progress. Arab governments should be held accountable for their UN commitments to
      address the crisis. Engagement in the global monitoring framework for non
      communicable diseases should promote accountability for effective action. The
      human and economic burden leaves no room for inaction. 

PMID- 24452045
TI  - The path towards universal health coverage in the Arab uprising countries
      Tunisia, Egypt, Libya, and Yemen.
AB  - The constitutions of many countries in the Arab world clearly highlight the role
      of governments in guaranteeing provision of health care as a right for all
      citizens. However, citizens still have inequitable health-care systems. One
      component of such inequity relates to restricted financial access to health-care
      services. The recent uprisings in the Arab world, commonly referred to as the
      Arab spring, created a sociopolitical momentum that should be used to achieve
      universal health coverage (UHC). At present, many countries of the Arab spring
      are considering health coverage as a priority in dialogues for new constitutions
      and national policy agendas. UHC is also the focus of advocacy campaigns of a
      number of non-governmental organisations and media outlets. As part of the health
      in the Arab world Series in The Lancet, this report has three overarching
      objectives. First, we present selected experiences of other countries that had
      similar social and political changes, and how these events affected their path
      towards UHC. Second, we present a brief overview of the development of health
      care systems in the Arab world with regard to health-care coverage and financing,
      with a focus on Egypt, Libya, Tunisia, and Yemen. Third, we aim to integrate
      historical lessons with present contexts in a roadmap for action that addresses
      the challenges and opportunities for progression towards UHC. 

PMID- 24452046
TI  - Changing therapeutic geographies of the Iraqi and Syrian wars.
AB  - The health consequences of the ongoing US-led war on terror and civil armed
      conflicts in the Arab world are much more than the collateral damage inflicted on
      civilians, infrastructure, environment, and health systems. Protracted war and
      armed conflicts have displaced populations and led to lasting transformations in
      health and health care. In this report, we analyse the effects of conflicts in
      Iraq and Syria to show how wars and conflicts have resulted in both the
      militarisation and regionalisation of health care, conditions that complicate the
      rebuilding of previously robust national health-care systems. Moreover, we show
      how historical and transnational frameworks can be used to show the long-term
      consequences of war and conflict on health and health care. We introduce the
      concept of therapeutic geographies--defined as the geographic reorganisation of
      health care within and across borders under conditions of war.

PMID- 24452047
TI  - The making of the Lancet Series on health in the Arab world.

PMID- 24452048
TI  - Importance of research networks: the Reproductive Health Working Group, Arab
      world and Turkey.

PMID- 24452049
TI  - State formation and underdevelopment in the Arab world.

PMID- 24452050
TI  - Research and activism for tobacco control in the Arab world.

PMID- 24452051
TI  - Health and ecological sustainability in the Arab world: a matter of survival.
AB  - Discussions leading to the Rio+20 UN conference have emphasised the importance of
      sustainable development and the protection of the environment for future
      generations. The Arab world faces large-scale threats to its sustainable
      development and, most of all, to the viability and existence of the ecological
      systems for its human settlements. The dynamics of population change, ecological
      degradation, and resource scarcity, and development policies and practices, all
      occurring in complex and highly unstable geopolitical and economic environments,
      are fostering the poor prospects. In this report, we discuss the most pertinent
      population-environment-development dynamics in the Arab world, and the two-way
      interactions between these dynamics and health, on the basis of current data. We
      draw attention to trends that are relevant to health professionals and
      researchers, but emphasise that the dynamics generating these trends have
      implications that go well beyond health. We argue that the current discourse on
      health, population, and development in the Arab world has largely failed to
      convey a sense of urgency, when the survival of whole communities is at stake.
      The dismal ecological and development records of Arab countries over the past two
      decades call for new directions. We suggest that regional ecological integration
      around exchange of water, energy, food, and labour, though politically difficult
      to achieve, offers the best hope to improve the adaptive capacity of individual
      Arab nations. The transformative political changes taking place in the Arab world
      offer promise, indeed an imperative, for such renewal. We call on policy makers,
      researchers, practitioners, and international agencies to emphasise the urgency
      and take action. 

PMID- 24452052
TI  - Health and contemporary change in the Arab world.

PMID- 24452054
TI  - Primary cardiac angiosarcoma - a review.
AB  - Primary cardiac neoplasms are extremely rare. Angiosarcoma is the most commonly
      seen histological subtype and is characterized by its permeating and destructive
      nature. Unfortunately, primary cardiac angiosarcoma is often overlooked as an
      initial diagnosis because of its rarity. Since the time it was first identified
      in 1934, little progress has been made in improving survival outcome. Complete or
      partial surgical resection is still the best option for palliation, with little
      hope for cure. Improvements have been made in the ability to view and distinguish
      tumors. Echocardiography is one of the most useful diagnostic tools because of
      its high sensitivity; therefore, CT and MR images are often used to detect sites
      of metastatic disease. Immunohistochemistry staining can also be employed as an
      adjunctive diagnostic tool. CD31, CD34, FLI-1, and von Willebrand factor are the
      most commonly used markers in detecting tumors of endothelial origin. However,
      due to the vast heterogeneity within a tumor, immunohistochemistry staining can
      be quite variable. Surgical resection remains the standard modality of treatment.
      Primary cardiac angiosarcoma is largely resistant to chemotherapy and/or
      radiation. However, the exact benefit and its place in a multimodality treatment
      regimen are still under investigation. 

PMID- 24452053
TI  - The effects of pdr1, djr1.1 and pink1 loss in manganese-induced toxicity and the
      role of alpha-synuclein in C. elegans.
AB  - Parkinson's disease (PD) is a neurodegenerative brain disorder characterized by
      selective dopaminergic (DAergic) cell loss that results in overt motor and
      cognitive deficits. Current treatment options exist to combat PD symptomatology,
      but are unable to directly target its pathogenesis due to a lack of knowledge
      concerning its etiology. Several genes have been linked to PD, including three
      genes associated with an early-onset familial form: parkin, pink1 and dj1. All
      three genes are implicated in regulating oxidative stress pathways. Another
      hallmark of PD pathophysiology is Lewy body deposition, associated with the gain
      of-function genetic risk factor alpha-synuclein. The function of alpha-synuclein
      is poorly understood, as it shows both neurotoxic and neuroprotective activities
      in PD. Using the genetically tractable invertebrate Caenorhabditis elegans (C.
      elegans) model system, the neurotoxic or neuroprotective role of alpha-synuclein
      upon acute Mn exposure in the background of mutated pdr1, pink1 or djr1.1 was
      examined. The pdr1 and djr1.1 mutants showed enhanced Mn accumulation and
      oxidative stress that was reduced by alpha-synuclein. Moreover, DAergic
      neurodegeneration, while unchanged with Mn exposure, returned to wild-type (WT)
      levels for pdr1, but not djr1.1 mutants expressing alpha-synuclein. Taken
      together, this study uncovers a novel, neuroprotective role for WT human alpha
      synuclein in attenuating Mn-induced toxicity in the background of PD-associated
      genes, and further supports the role of extracellular dopamine in exacerbating Mn
      neurotoxicity. 

PMID- 24452056
TI  - Optical study of lithographically defined, subwavelength plasmonic wires and
      their coupling to embedded quantum emitters.
AB  - We present an optical investigation of surface plasmon polaritons propagating
      along nanoscale Au-wires, lithographically defined on GaAs substrates. A two-axis
      confocal microscope was used to perform spatially and polarization resolved
      measurements in order to confirm the guiding of surface plasmon polaritons over
      lengths ranging from 5 to 20 MUm along nanowires with a lateral dimension of only
      ~ 100 nm. Finite difference time domain simulations are used to corroborate our
      experimental observations, and highlight the potential to couple proximal quantum
      emitters to propagating plasmon modes in such extreme subwavelength devices. Our
      findings are of strong relevance for the development of semiconductor based
      integrated plasmonic and active quantum plasmonic nanosystems that merge quantum
      emitters with nanoscale plasmonic elements.

PMID- 24452055
TI  - Detecting phase-amplitude coupling with high frequency resolution using adaptive
      decompositions.
AB  - BACKGROUND: Phase-amplitude coupling (PAC)--the dependence of the amplitude of
      one rhythm on the phase of another, lower-frequency rhythm - has recently been
      used to illuminate cross-frequency coordination in neurophysiological activity.
      An essential step in measuring PAC is decomposing data to obtain rhythmic
      components of interest. Current methods of PAC assessment employ narrowband
      Fourier-based filters, which assume that biological rhythms are stationary,
      harmonic oscillations. However, biological signals frequently contain irregular
      and nonstationary features, which may contaminate rhythms of interest and
      complicate comodulogram interpretation, especially when frequency resolution is
      limited by short data segments. NEW METHOD: To better account for
      nonstationarities while maintaining sharp frequency resolution in PAC
      measurement, even for short data segments, we introduce a new method of PAC
      assessment which utilizes adaptive and more generally broadband decomposition
      techniques - such as the empirical mode decomposition (EMD). To obtain high
      frequency resolution PAC measurements, our method distributes the PAC associated
      with pairs of broadband oscillations over frequency space according to the time
      local frequencies of these oscillations. COMPARISON WITH EXISTING METHODS: We
      compare our novel adaptive approach to a narrowband comodulogram approach on a
      variety of simulated signals of short duration, studying systematically how
      different types of nonstationarities affect these methods, as well as on EEG
      data. CONCLUSIONS: Our results show: (1) narrowband filtering can lead to poor
      PAC frequency resolution, and inaccuracy and false negatives in PAC assessment;
      (2) our adaptive approach attains better PAC frequency resolution and is more
      resistant to nonstationarities and artifacts than traditional comodulograms.

PMID- 24452057
TI  - Regulation of EB1/3 proteins by classical MAPs in neurons.
AB  - Microtubules (MTs) are key cytoskeletal elements in developing and mature
      neurons. MT reorganization underlies the morphological changes that occur during
      neuronal development. Furthermore, MTs contribute to the maintenance of neuronal
      architecture, enable intracellular transport and act as scaffolds for signaling
      molecules. Thus, a fine-tuned regulation of MT dynamics and stability is crucial
      for the correct differentiation and functioning of neurons. Different types of
      proteins contribute to the regulation of the MT state, such as plus-end tracking
      proteins (+TIPs), which interact with the plus-ends of growing microtubules, and
      classical microtubule-associated proteins (MAPs), which bind along the
      microtubule lattice. Recent evidence indicates that MAPs interplay with End
      Binding Proteins (EBs), the core +TIPs, in neuronal cells. This might contribute
      to the orchestrated regulation of MT dynamics in neurons. In this mini-review
      article, we address recent research on the neuronal crosstalk between EBs and
      classical MAPs and speculate on its possible functional relevance. 

PMID- 24452058
TI  - Early prediction of response of sorafenib on hepatocellular carcinoma by CT
      perfusion imaging: an animal study.
AB  - OBJECTIVE: This study evaluated the feasibility of CT perfusion parameters for
      the early efficacy prediction of sorafenib in the treatment of hepatocellular
      carcinoma (HCC) in rats. METHODS: CT hepatic perfusion measurements were
      performed in the livers of 40 rats implanted with rat HCC. The rats in the
      experimental group (n = 28) were treated by oral gavage with sorafenib (20 mg per
      day), whereas the rats in the control group (n = 12) were treated by normal
      saline. Rats were classified into the responder group if the maximum diameter of
      their tumour had decreased 21 days after treatment, whereas the other rats were
      classified into the non-responder group. Data were analysed using the Pearson
      correlation analysis or analysis of variance. RESULTS: CT perfusion was used to
      depict haemodynamic changes before and after treatment. The arterial liver
      perfusion was significantly decreased in the responder group on Day 11 after
      treatment with sorafenib (from 71.5 to 53.4 ml min(-1) 100 ml(-1)), whereas no
      significant changes were observed in the non-responder group (p = 0.87). The
      maximum diameter of the tumour was also significantly decreased in the responder
      group on Day 21 after treatment (p = 0.042), whereas the maximum tumour diameter
      was significantly increased in the control group (p = 0.001). CONCLUSION AND
      ADVANCES IN KNOWLEDGE: CT perfusion could be used to quantitatively analyse the
      haemodynamic changes in the treatment of HCC with sorafenib, which indicates that
      this approach may be developed for the early prediction of treatment efficacy for
      sorafenib.

PMID- 24452059
TI  - Should the justification of medical exposures take account of radiation risks
      from previous examinations?
AB  - With the growing availability of dose histories for patients, the question of
      whether previous diagnostic radiation exposures should affect decisions on future
      examinations is coming into sharper focus. This article discusses ways in which
      cumulative dose information may affect our thinking in justifying exposures.
      Based on a common tendency to see a connection between past and future events
      even where we know them to be independent-the gambler's fallacy-we may find
      ourselves treating past risks as if they contribute to the present risk. We take
      the example of two patients scheduled for CT scans, one with no previous
      diagnostic radiation exposures, the other with a history of previous CT scans, to
      show that the risks, and justification process, are equivalent in both cases. For
      the patient with a history of diagnostic exposures, there are only two
      possibilities: either harm has been caused or there has been no effect. If
      previous CT examinations have not caused harm, then, as past risks, they are
      irrelevant. The patient is in precisely the same position with regard to risk as
      a patient with no dose history. If harm has been caused, avoiding further
      diagnostic exposures does not change this outcome; again in this case, a
      justified radiation examination should proceed. We argue that bringing dose
      history into the decision process for justifying examinations is contrary to our
      understanding of risk for low-dose radiation and, rather than improving patient
      safety, would unnecessarily restrict access to radiation-based diagnostic
      examinations. 

PMID- 24452060
TI  - Synthesis of an efficient heteroatom-doped carbon electro-catalyst for oxygen
      reduction reaction by pyrolysis of protein-rich pulse flour cooked with SiO2
      nanoparticles.
AB  - Development of a highly durable, fuel-tolerant, metal-free electro-catalyst for
      oxygen reduction reaction (ORR) is essential for robust and cost-effective Anion
      Exchange Membrane Fuel Cells (AEMFCs). Herein, we report the development of a
      nitrogen-doped (N-doped) hierarchically porous carbon-based efficient ORR
      electrocatalyst from protein-rich pulses. The process involves 3D silica
      nanoparticle templating of the pulse flour(s) followed by their double pyrolysis.
      The detailed experiments are performed on gram flour (derived from chickpeas)
      without any in situ/ex situ addition of dopants. The N-doped porous carbon thus
      generated shows remarkable electrocatalytic activity towards ORR in the alkaline
      medium. The oxygen reduction on this material follows the desired 4-electron
      transfer mechanism involving the direct reduction pathway. Additionally, the
      synthesized carbon catalyst also exhibits good electrochemical stability and fuel
      tolerance. The results are also obtained and compared with the case of soybean
      flour having higher nitrogen content to highlight the significance of different
      parameters in the ORR catalyst performance. 

PMID- 24452061
TI  - Rapid recovery of soil bacterial communities after wildfire in a Chinese boreal
      forest.
AB  - Fires affect hundreds of millions of hectares annually. Above-ground community
      composition and diversity after fire have been studied extensively, but effects
      of fire on soil bacterial communities remain largely unexamined despite the
      central role of bacteria in ecosystem recovery and functioning. We investigated
      responses of bacterial community to forest fire in the Greater Khingan Mountains,
      China, using tagged pyrosequencing. Fire altered soil bacterial community
      composition substantially and high-intensity fire significantly decreased
      bacterial diversity 1-year-after-burn site. Bacterial community composition and
      diversity returned to similar levels as observed in controls (no fire) after 11
      years. The understory vegetation community typically takes 20-100 years to reach
      pre-fire states in boreal forest, so our results suggest that soil bacteria could
      recover much faster than plant communities. Finally, soil bacterial community
      composition significantly co-varied with soil pH, moisture content, NH4(+)
      content and carbon/nitrogen ratio (P < 0.05 in all cases) in wildfire-perturbed
      soils, suggesting that fire could indirectly affect bacterial communities by
      altering soil edaphic properties. 

PMID- 24452063
TI  - Preschoolers' hair cortisol levels are linked to parental income.

PMID- 24452064
TI  - Medicinal herbs and therapeutic drugs interactions.
AB  - People mistakenly think that all herbs are safe, because of the fact that they
      are natural, and the use of herbal medication is growing. Aspects of the
      efficacy, safety, and quality of herbal or natural products are the subjects of
      on-going debates. Concurrent administration of herbs may interfere with the
      effect of drugs. Lack of knowledge of the interaction potential together with an
      underreporting of herbal use poses a challenge for health care providers and a
      safety concern for patients. A good understanding of the mechanisms of herb-drug
      interactions is also essential for assessing and minimizing clinical risks.
      Examples of herbal medicine-pharmaceutical drug interactions of commonly used
      herbs are presented. The potential pharmacokinetic and pharmacodynamic basis of
      such interactions is discussed, as well as the challenges associated with the
      identification and prediction of herb-drug interactions.

PMID- 24452062
TI  - Activation of membrane estrogen receptors attenuates opioid receptor-like1
      receptor-mediated antinociception via an ERK-dependent non-genomic mechanism.
AB  - To our knowledge, the present data are the first to demonstrate that activation
      of membrane estrogen receptors (mERs) abolishes opioid receptor-like 1 (ORL1)
      receptor-mediated analgesia via extracellular signal-regulated kinase (ERK)
      dependent non-genomic mechanisms. Estrogen was shown previously to both attenuate
      ORL1-mediated antinociception and down-regulate the ORL1 gene expression. The
      present study investigated whether non-genomic mechanisms contribute to estrogen
      induced attenuation of ORL1-mediated antinociception by the mERs GPR30, Gq
      coupled mER, ERalpha, and ERbeta. E2BSA [beta-estradiol-6-(O-carboxymethyl)oxime:
      bovine serum albumin] (0.5mM), a membrane impermeant analog of estradiol,
      injected intrathecally immediately prior to orphanin FQ (OFQ;10 nmol), the
      endogenous ligand for the ORL1 receptor, abolished OFQ's antinociceptive effect
      in both male and ovariectomized (OVX) female rats, assessed using the heat
      induced tail-flick assay. This effect was not altered by protein synthesis
      inhibitor, anisomycin (125 MUg), given intrathecally 15 min prior to E2BSA and
      OFQ. Intrathecal application of selective receptor agonists permitted the
      relative contributions of various estrogen receptors in mediating this blockade
      of the antinociceptive response of OFQ. Activation of GPR30, Gq-mER, ERalpha, but
      not ERbeta abolished ORL1-mediated antinociception in males and OVX females.
      E2BSA produced a parallel and significant increase in the phosphorylation of ERK
      2 only in OVX females, and pre-treatment with MEK/ERK 1/2 inhibitor, U0126 (10
      MUg), blocked the mER-mediated abolition of ORL1-mediated antinociception in OVX
      females. Taken together, the data are consistent with the interpretations that
      mER activation attenuates ORL1-mediated antinociception through a non-genomic,
      ERK 2-dependent mechanism in females.

PMID- 24452065
TI  - Pharmacokinetics of total and unbound prednisone and prednisolone in stable
      kidney transplant recipients with diabetes mellitus.
AB  - BACKGROUND: The corticosteroid prednisone is an important component of
      posttransplantation immunosuppressive therapy. Pharmacokinetic parameters of
      prednisone or its pharmacologically active metabolite, prednisolone, are not well
      characterized in transplant recipients. The objective of this study was to
      compare the pharmacokinetics of total and unbound prednisone and prednisolone in
      diabetic and nondiabetic stable kidney transplant recipients and to evaluate the
      factors influencing plasma protein binding of prednisolone. METHODS: Prednisone
      and prednisolone concentration-time profiles were obtained in 20 diabetic and 18
      nondiabetic stable kidney transplant recipients receiving an oral dose of 5-10 mg
      prednisone per day. In addition to drug and metabolite exposures, factors
      influencing prednisolone protein binding were evaluated using a nonlinear mixed
      effects modeling approach. This model takes into account the binding of
      prednisolone and cortisol to corticosteroid-binding globulin (CBG) in a saturable
      fashion and binding of prednisolone to albumin in a nonsaturable fashion.
      Finally, we have investigated the influence of several covariates including
      diabetes, glucose concentration, hemoglobin A1c, creatinine clearance, body mass
      index, gender, age, and time after transplantation on the affinity constant (K)
      between corticosteroids and their binding proteins. RESULTS: In patients with
      diabetes, the values of dose-normalized area under the concentration-time curves
      were 27% and 23% higher for total and unbound prednisolone, respectively.
      Moreover, the ratio of total prednisolone to prednisone concentrations
      (active/inactive forms) was higher in diabetic subjects (P < 0.001). Modeling
      protein binding results revealed that the affinity constant of corticosteroid
      binding globulin-prednisolone (KCBG,PL) was related to the patient's gender and
      diabetes status. CONCLUSIONS: Higher prednisolone exposure could potentially lead
      to the increased risk of corticosteroid-related complications in diabetic kidney
      transplant recipients.

PMID- 24452066
TI  - Use of graft-derived cell-free DNA as an organ integrity biomarker to reexamine
      effective tacrolimus trough concentrations after liver transplantation.
AB  - BACKGROUND: Immunosuppressant therapeutic ranges for transplant patients have
      traditionally been established by indirect clinical means. However, "liquid
      biopsy" methods measuring graft-derived cell-free DNA (GcfDNA) in blood directly
      interrogate donor organ integrity. This study was performed to determine whether
      GcfDNA quantification could be used to reexamine minimally effective trough
      tacrolimus (Tacro) concentrations in liver transplantation (LTx) patients.
      METHODS: As part of a large prospective study to demonstrate the ability of
      GcfDNA to identify early graft rejection, 10 adult white LTx patients [8 men, 2
      women, 3 hepatitis C virus (HCV) positive; mean +/- SD age (years) = 56 +/- 9.4]
      had simultaneous GcfDNA and whole-blood trough Tacro concentrations measured
      between days 5 and 30 after LTx. Samples were analyzed using droplet digital
      polymerase chain reaction for GcfDNA and liquid chromatography tandem mass
      spectrometry for Tacro. GcfDNA and trough Tacro concentrations were then compared
      to identify Tacro concentrations associated with intact graft integrity. RESULTS:
      Although there were large individual differences, there was a highly significant
      (Fisher P = 0.00002) segregation between whole-blood Tacro concentrations of >=8
      MUg/L and normal (<=10%) GcfDNA percentages. The best discrimination in this
      population between effective and ineffective trough Tacro concentrations was
      estimated to be at 6.8 MUg/L (P < 10(-7)). Compared with HCV- patients (n = 7),
      the 3 HCV+ patients had more variable associations between GcfDNA percentages and
      Tacro concentrations. CONCLUSIONS: Direct measurement of graft integrity using
      GcfDNA was useful to confirm the lower limit of the therapeutic ranges for trough
      Tacro concentrations after LTx. It would probably be useful to do so also for
      other immunosuppressant drugs and after other solid organ transplants. The method
      might be especially useful to detect graft injury during immunosuppressant dose
      minimization strategies.

PMID- 24452067
TI  - Vancomycin monitoring in children using bayesian estimation.
AB  - BACKGROUND: Optimal monitoring of vancomycin in children needs evaluation using
      the exposure target with area under the curve (AUC) of the serum concentrations
      versus time over 24 hours. Our study objectives were to: (1) compare the accuracy
      and precision of vancomycin AUC estimations using 2 sampling strategies-1 serum
      concentration sample (1S, near trough) versus 2 samples (2S, near peak and
      trough) against the rich sample (RS) method; and (2) determine the performance of
      these strategies in predicting future AUC against an internal validation sample
      (VS). METHODS: This was a retrospective cohort study using population-based
      pharmacokinetic modeling with Bayesian post hoc individual estimations in
      nonlinear mixed effects modeling (version 7.2). Pediatric subjects 3 months-21
      years of age who received vancomycin >=48 hours and had more than 3 drug samples
      within the first <=96 hours of therapy were enrolled. Outcome measures were the
      accuracy, precision, and internal predictive performance of AUC estimations using
      2 monitoring strategies (ie, 1S versus 2S) against the RS (which was derived from
      modeling all serum vancomycin concentrations obtained anytime during therapy) and
      VS (from serum concentrations obtained after 96 hours of therapy). RESULTS:
      Analysis included 138 subjects with 712 vancomycin serum concentrations. Median
      age was 6.1 (interquartile range, 2.2-12.2) years, weight 22 (13-38) kg, and
      baseline serum creatinine 0.37 (0.30-0.50) mg/dL. Both accuracy and precision
      were improved with the 2S, compared with 1S, for AUC estimations (-2.0% versus 
      7.6% and 10.3% versus 12.8%, respectively) against the RS. Improved accuracy and
      precision were also observed for 2S when evaluated against VS in predicting
      future AUC. CONCLUSIONS: Compared with 1S, the 2S sampling strategy for
      vancomycin monitoring improved accuracy and precision in estimating and
      predicting future AUC. Evaluating 2 drug concentrations in children may be
      prudent to ensure adequate drug exposure.

PMID- 24452068
TI  - Serum concentrations of hydroxybupropion for dose optimization of depressed
      patients treated with bupropion.
AB  - BACKGROUND: Bupropion is a dopamine and norepinephrine reuptake inhibitor
      approved for the treatment of depression and smoking cessation. According to the
      recently published reviews, it is a candidate for therapeutic drug monitoring
      (TDM) to improve therapeutic outcomes and reduce risks of intolerability or
      intoxication. In practice, however, the use of TDM is limited due to the chemical
      instability of bupropion. This investigation sought to determine if the major,
      active, and chemically stable metabolite 4-hydroxybupropion is a suitable measure
      to guide antidepressant drug therapy with bupropion. METHODS: 4-Hydroxybupropion
      serum levels were measured using a newly developed and validated high-performance
      liquid chromatography assay with ultraviolet detection. They correlated with
      therapeutic effects measured by the clinical global impression scale for
      improvement. RESULTS: The study included 52 patients (50% women). Patients who
      were markedly improved according to the clinical global impression scale score
      had significantly (P = 0.042) higher 4-hydroxybupropion serum levels than those
      with moderate or minimal improvement (mean +/- SD, 1113 +/- 576, 825 +/- 398, and
      475 +/- 331 ng/mL, respectively). Analysis of receiver operating characteristics
      revealed significant predictive properties of 4-hydroxybupropion serum levels (P
      = 0.002) for marked improvement with a lower threshold level of 858 ng/mL. Under
      similar mean doses (265 +/- 107 versus 239 +/- 100 mg, respectively), women
      attained significantly higher serum levels than men (1050 +/- 524 versus 589 +/-
      352 ng/mL, respectively) and exhibited a better therapeutic effect (P = 0.018).
      CONCLUSIONS: Despite multiple limitations of this naturalistic study, evidence
      could be given that the measurement of 4-hydroxybupropion in serum is suitable to
      perform TDM for bupropion. Blood levels should be above 860 ng/mL to attain
      therapeutic improvement. Potential sex differences in bupropion pharmacokinetics,
      probably due to differential activities of CYP2B6, should be taken into account
      when the drug is prescribed.

PMID- 24452069
TI  - Determination of amphetamine and methylphenidate in exhaled breath of patients
      undergoing attention-deficit/hyperactivity disorder treatment.
AB  - OBJECTIVES: It has been discovered recently that exogenous substances are
      detectable in exhaled breath after intake. Exhaled breath therefore constitutes a
      new possible matrix in clinical pharmacology and toxicology. The present work was
      aimed at exploring this possibility further by a study on patients treated for
      attention-deficit/hyperactivity disorder with D-amphetamine and methylphenidate.
      METHODS: Thirteen patients (age range: 32-61 years; 5 women) were included in the
      study, and breath and urine samples were collected at different times in the dose
      interval. Analyses of breath and urine samples were done with liquid
      chromatography-mass spectrometry methods. Urine was examined for amphetamine,
      methylphenidate, and its metabolite ritalinic acid. RESULTS: Among the 9 patients
      who received D-amphetamine medication in daily doses of 20-100 mg, amphetamine
      was detected in all subjects in amounts ranging from 1200 to 30,800 picogram per
      filter. Among 8 patients receiving methylphenidate medication in daily doses of
      80-400 mg, it was detected and quantified in 7 of the cases in amounts ranging
      from 150 to 10,400 picogram per filter and ritalinic acid was detected and
      quantified in 3 of the cases ranging from 35 to 360 picogram per filter. In 1
      case, methylphenidate was only detectable in breath and urine, whereas ritalinic
      acid was quantifiable in urine, which could indicate noncompliance, with the 4
      hours of dose regimen prescribed. In a number of cases, the sampling was
      performed 24 hours after the last dose intake. Identification of amphetamine and
      methylphenidate was based on correct chromatographic retention time and correct
      product ion ratio with detection performed in selected reaction monitoring mode.
      CONCLUSIONS: The results confirm that amphetamine is present in exhaled breath
      after intake and demonstrate for the first time the presence of methylphenidate
      and ritalinic acid after its intake. This gives further support to the potential
      use of exhaled breath for detecting drug intake.

PMID- 24452070
TI  - A review of evidence-based early intervention for behavioural problems in
      children with autism spectrum disorder: the core components of effective
      programs, child-focused interventions and comprehensive treatment models.
AB  - PURPOSE OF REVIEW: This article reviews recent evidence and other earlier
      relevant articles regarding early intervention studies for children with autism
      spectrum disorder (ASD). RECENT FINDINGS: There is a well-established body of
      empirical evidence for the effectiveness of Early Intensive Behavioural
      Intervention (EIBI) with young children with ASD. The importance of parent skills
      training, education and positive behaviour support is also a key factor in
      influencing outcomes. Drug treatment is of short-term benefit for disruptive
      behaviour but long-term outcome and metabolic side-effects have not been studied.
      SUMMARY: Few studies have measured the long-term value and effectiveness of early
      intervention treatments, and currently there are no articles published on effects
      into adulthood of such treatments. Such research would indicate whether early
      intervention results in reduced reliance on health services into adulthood.

PMID- 24452071
TI  - Substituent effect on the photoinduced structural change of Cu(I) complexes
      observed by femtosecond emission spectroscopy.
AB  - The Cu(I) complexes having phenanthroline derivatives as ligands are known to
      exhibit photo-induced 'flattening' structural change in the metal-to-ligand
      charge transfer (MLCT) excited state. Our recent ultrafast spectroscopic studies
      of [Cu(dmphen)2](+) (dmphen = 2,9-dimethyl-1,10-phenanthroline) showed that the
      photo-induced structural change predominantly occurs in the S1 state on a
      subpicosecond time scale, with the appearance of the 'perpendicular' S1 state
      before the structural change. In this work, we carried out femto/picosecond time
      resolved emission spectroscopy of [Cu(phen)2](+) (phen = 1,10-phenanthroline) and
      [Cu(dpphen)2](+) (dpphen = 2,9-diphenyl-1,10-phenanthroline) in dichloromethane
      with the S2 <- S0 photo-excitation to examine the substituent effect on the
      ultrafast structural change. The femtosecond time-resolved emission spectra of
      the two complexes exhibit ultrafast fluorescence changes that are attributed to
      the structural change in the S1 state after fast (50-100 fs) S2 -> S1 internal
      conversion. By comparing with the dynamics of [Cu(dmphen)2](+), it was found that
      the time constant of the structural change increases as the substituents at 2-
      and 9- positions of the ligand become bulkier, i.e., [Cu(phen)2](+) (200 fs) <
      [Cu(dmphen)2](+) (660 fs) < [Cu(dpphen)2](+) (920 fs). This implies that the
      complex needs a longer time to flatten with the bulkier substituent. This
      demonstrates that the dynamics of the photo-induced structural change of Cu(I)
      complexes is substantially affected by the substituent of the ligand. The
      dynamics of the ultrafast structural change and the substituent effect are
      discussed with the multidimensional S1 potential energy surface of Cu(I)
      complexes.

PMID- 24452072
TI  - The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis.
AB  - Aberrant activation of Wnt signalling results in colorectal tumours. Lgr5 is
      specifically expressed in stem cells of the intestine and has an essential role
      in maintaining tissue homeostasis. Lgr5-positive stem cells are responsible for
      the intestinal adenoma initiated by mutations in adenomatous polyposis coli.
      Furthermore, Lgr5 interacts with R-spondins and thereby activates Wnt signalling.
      However, the function of Lgr5 in colorectal tumourigenesis is unclear. Here we
      show that LGR5 is required for the tumourigenicity of colorectal cancer cells. We
      show that the transcription factor GATA6 directly enhances the expression of
      LGR5. We further demonstrate that GATA6 is upregulated in colorectal cancer cells
      due to the downregulation of miR-363, which directly targets GATA6. Moreover, we
      show that overexpression of miR-363 suppresses the tumourigenicity of colorectal
      cancer cells. These results suggest that the miR-363-GATA6-LGR5 pathway is
      critical for colorectal tumourigenesis and would be a promising target for the
      treatment of colorectal cancer. 

PMID- 24452073
TI  - Alternation and tunable composition in hydrogen bonded supramolecular copolymers.
AB  - Sequence control in supramolecular copolymers is limited by the selectivity of
      the associating monomer end groups. Here we introduce the use of monomers with
      aminopyrimidinone and aminohydroxynaphthyridine quadruple hydrogen bonding end
      groups, which both homodimerize, but form even stronger heterodimers. These
      features allow the formation of supramolecular copolymers with a tunable
      composition and a preference for alternating sequences. 

PMID- 24452074
TI  - Autoinflammatory diseases.
AB  - Autoinflammatory diseases represent an expanding spectrum of genetic and non
      genetic inflammatory diseases characterized by recurrent episodes of fever and
      systemic inflammation affecting the eyes, joints, skin, and serosal surfaces.
      Thus, these syndromes are recognized as disorders of innate immunity. Confirming
      this view, most autoinflammatory diseases are uniquely responsive to IL-1beta
      blockade. Although many autoinflammatory diseases have a genetic cause,
      increasing evidence indicates that the degree of cell stress concurs to the
      severity of the disease phenotype. In this mini-review, I will discuss the recent
      advances on pathogenesis, pathophysiology and therapeutic approaches in
      autoinflammatory syndromes. 

PMID- 24452078
TI  - The role of glutathione in mercury tolerance resembles its function under cadmium
      stress in Arabidopsis.
AB  - Recent research efforts have highlighted the importance of glutathione (GSH) as a
      key antioxidant metabolite for metal tolerance in plants. Little is known about
      the mechanisms involved in stress due to mercury (Hg), one of the most hazardous
      metals to the environment and human health. To understand the implication of GSH
      metabolism for Hg tolerance, we used two gamma-glutamylcysteine synthetase
      (gammaECS) Arabidopsis thaliana allele mutants (rax1-1 and cad2-1) and a
      phytochelatin synthase (PCS) mutant (cad1-3). The leaves of these mutants and of
      wild type (Col-0) were infiltrated with a solution containing Cd or Hg (0, 3 and
      30 MUM) and incubated for 24 and 48 h. The formation of phytochelatins (PCs) in
      the leaf extracts was followed by two different HPLC-based methods and occurred
      in Col-0, cad2-1 and rax1-1 plants exposed to Cd, whereas in the Hg treatments,
      PCs accumulated mainly in Col-0 and rax1-1, where Hg-PC complexes were also
      detected. ASA and GSH/GSSG levels increased under moderate metal stress
      conditions, accompanied by increased GSH reductase (GR) activity and expression.
      However, higher metal doses led to a decrease in the analysed parameters, and
      stronger toxic effects appeared with 30 MUM Hg. The GSH concentration was
      significantly higher in rax1-1 (70% of Col-0) than in cad2-1 (40% of Col-0). The
      leaves of rax1-1 were less sensitive than cad2-1, in accordance with the greater
      expression of gammaECS in rax1-1. Our results underline the existence of a
      minimal GSH concentration threshold needed to minimise the toxic effects exerted
      by Hg. 

PMID- 24452079
TI  - Lupus vasculopathy: Diagnostic, pathogenetic and therapeutic considerations.
AB  - A rare form of vascular disease in systemic lupus erythematosus (SLE), lupus
      vasculopathy is characterized by necrosis and accumulation of immunoglobulins
      (IGs) and complements in the wall of arterioles and small arteries resulting in
      luminal narrowing. Lupus vasculopathy often accompanies lupus nephritis and
      portends a poor prognosis. Although there is general agreement on the treatment
      of lupus nephritis, effective treatment strategies for lupus vasculopathy remain
      to be defined. We report a 20-year-old woman with SLE who presented with
      generalized tonic-clonic seizure. Her immunosuppressive regimen consisted of
      mycophenolate mofetil, prednisone and hydroxychloroquine. On physical
      examination, she was Cushingoid in appearance and hypertensive. Laboratory tests
      indicated renal disease. Coagulation studies disclosed de novo lupus
      anticoagulant. Magnetic resonance imaging of the brain demonstrated acute focal
      cerebral hemorrhage. Echocardiography revealed reduced ejection fraction and
      severe mitral regurgitation. Despite high-dose glucocorticoids and mycophenolate
      mofetil, renal function remained poor. Kidney biopsy demonstrated lupus
      vasculopathy and glomerulonephritis. Plasma exchange therapy and intravenous
      cyclophosphamide were administered. Over the ensuing four weeks, renal function
      improved, complement levels increased, autoantibody titers decreased and lupus
      anticoagulant disappeared. In conclusion, lupus vasculopathy can occur in SLE
      despite a heavy immunosuppressive regimen. Antiphospholipid antibodies might be
      involved in the pathogenesis of lupus vasculopathy. Plasma exchange therapy in
      conjunction with intravenous cyclophosphamide may represent an effective
      treatment strategy for lupus vasculopathy. 

PMID- 24452080
TI  - Actomyosin-dependent formation of the mechanosensitive talin-vinculin complex
      reinforces actin anchoring.
AB  - The force generated by the actomyosin cytoskeleton controls focal adhesion
      dynamics during cell migration. This process is thought to involve the mechanical
      unfolding of talin to expose cryptic vinculin-binding sites. However, the ability
      of the actomyosin cytoskeleton to directly control the formation of a talin
      vinculin complex and the resulting activity of the complex are not known. Here we
      develop a microscopy assay with pure proteins in which the self-assembly of
      actomyosin cables controls the association of vinculin to a talin-micropatterned
      surface in a reversible manner. Quantifications indicate that talin refolding is
      limited by vinculin dissociation and modulated by the actomyosin network
      stability. Finally, we show that the activation of vinculin by stretched talin
      induces a positive feedback that reinforces the actin-talin-vinculin association.
      This in vitro reconstitution reveals the mechanism by which a key molecular
      switch senses and controls the connection between adhesion complexes and the
      actomyosin cytoskeleton. 

PMID- 24452081
TI  - Duplex ultrasound, clinical score, thrombotic risk, and D-dimer testing for
      evidence based diagnosis and management of deep vein thrombosis and alternative
      diagnoses in the primary care setting and outpatient ward.
AB  - Deep vein thrombosis (DVT) has an annual incidence of 0.2% in the urban
      population. First episodes of calf vein thrombosis (CVT) and proximal DVT are
      frequently elicited by risk factors, including varicose veins, cancer,
      pregnancy/postpartum, oral contraceptives below the age of 50 years, immobility
      or surgery. Leg pain and tenderness in the calf and popliteal fossa on physical
      examination may result from other conditions than DVT labeled as alternative
      diagnosis (AD) Congenital venous thrombophilia is present in every third first
      DVT, increased FVIII in every fourth first DVT, and FV Leiden/FII mutation in 40%
      of women on oral anticonceptive pill before reaching the menopause. Routine
      thrombophilia testing for FV Leiden/prothrombin mutation and FVIII as main risk
      factor for venous thrombosis is recommended. Primary superficial venous
      thrombosis (SVT) and DVT patients with a autosomal dominant family history of DVT
      are candidates for thrombophilia testing for congenital AT, PC and PS deficiency.
      The requirement for a safe diagnostic strategy of CVT and DVT should be based on
      an objective post-test incidence of venous thromboembolism (VTE) of less than
      0.1% with a negative predictive value for exclusion of DVT of 99.9% during 3
      months follow-up. Modification of the Wells score by elimination of the "minus 2
      points" for AD is mandatory and will improve the diagnostic accuracy of CVT/DVT
      suspicion in the primary care setting and outpatient ward. The sequential use of
      complete DUS, ELISA D-dimer testing and modified clinical Wells' score assessment
      is safe and effective for the exclusion and diagnosis of CVT, DVT and AD. About
      10% to 20% of patients with DVT develop overt post-thrombotic syndrome (PTS) at
      one year post-DVT, and both PTS and DVT recurrences further increase to about 30%
      during long-term follow-up. Objective risk stratification of PTS complications
      using DUS for recanalization and reflux and D-dimer testing will become an
      integral part in routine clinical practice to assess the optimal duration of
      wearing medical elastic stockings and anticoagulation for the prevention DVT
      recurrence as the best option to reduce the incidence and costs of suffering from
      irreversible PTS. 

PMID- 24452082
TI  - Pycnogenol(r) and Centella Asiatica for asymptomatic atherosclerosis progression.
AB  - AIM: The aim of the study was to evaluate the effect of the nutritional
      supplements Pycnogenol and TECA (total triterpenic fraction of Centella Asiatica)
      on atherosclerosis progression in low-risk asymptomatic subjects with carotid or
      femoral non-stenosing plaques. METHODS: This was an observational pilot substudy
      of the San Valentino epidemiological cardiovascular study. The study included
      1363 subjects aged 45-60 without any conventional risk factors who had non
      stenosing atherosclerotic plaques (<50%) in at least one carotid or common
      femoral bifurcation, allocated into 6 groups: Group 1 (CONTROLS): management was
      based on education, exercise, diet and lifestyle changes. This same management
      plan was used in all groups; Group 2 Pycnogenol 50 mg/day; Group 3 Pycnogenol 100
      mg/day; Group 4 Aspirin 100 mg/day or Ticlopidine 250 mg/day if intolerant to
      aspirin; Group 5 Aspirin 100 mg/day and Pycnogenol 100 mg/day; Group 6 Pycnogenol
      100 mg/day plus TECA (total triterpenic fraction of Centella Asiatica) 100
      mg/day. There was a six monthly follow-up up to 30 months. Plaque progression was
      assessed using the ultrasonic arterial score based on the arterial wall
      morphology and the number of plaques that progressed from the non-stenotic to the
      stenotic group. A secondary endpoint was to evaluate the changes in oxidative
      stress at baseline and at 30 months. RESULTS: The ultrasonic score increased
      significantly in groups 1, 2 and 4 but not in groups 3, 5 and 6 suggesting a
      beneficial effect of Pycnogenol 100 mg. The percentage of plaques that progressed
      from class IV to class V was 8.4% in group 2, 5.3% in group 3, 4% in group 5 and
      1.1% in group 6 (P<0.0001) compared with 16.6% in group 4 (aspirin) and 21.3% in
      the control group suggesting a beneficial effect of Pycnogenol. The lowest rate
      of progression was in group 6 (Pycnogenol plus TECA). At 30 months, the oxidative
      stress in all the Pycnogenol groups was less than in the control group. The
      oxidative stress was lower in the Pycnogenol 100 mg group than the Pycnogenol 50
      mg group (P<0.0001). In the combined group of Pycnogenol and TECA the oxidative
      stress was less than the Pycnogenol alone (P<0.001). CONCLUSION: Pycnogenol and
      the combination of Pycnogenol+TECA appear to reduce the progression of
      subclinical arterial lesions in low-risk asymptomatic subjects. The reduction in
      plaque progression was associated with a reduction in oxidative stress. The
      results justify a large randomized controlled study to demonstrate the efficacy
      of the combined Pycnogenol and TECA prophylactic therapy in subclinical
      atherosclerosis.

PMID- 24452083
TI  - Anti-sympathetic action enhances statin's pleiotropic effects: the combined
      effect of rosuvastatin and atenolol on endothelial function.
AB  - AIM: Assessment of flow-mediated dilation (FMD) and nitroglycerin-mediated
      dilation (NMD) in the brachial artery by a new device (UNEXEF18G) has been
      reported to be excellent for evaluating endothelial function, and sympathetic
      overdrive can accelerate the atherosclerotic process. The purpose of this study
      was to investigate and confirm whether anti-sympathetic beta-blocking action can
      enhance the pleiotropic effects of statins. METHODS: FMD and NMD were measured
      using the UNEXEF18G before and after 4-week treatment of rosuvastatin (5 mg/day)
      with or without atenolol (25 mg/day) in 44 hypercholesterolemic patients (70+/-8
      years old, LDL-C >140 mg/dL) with hypertension. Patients were randomly allocated
      to two treatment arms: rosuvastatin alone (R-group, N.=22) and rosuvastatin with
      atenolol (RA-group, N.=22). RESULTS: Baseline FMD was not different between the
      two treatment arms, and both groups showed improvement in FMD (R-group, 3.48+/
      1.9% to 4.65+/-2.41%, P<0.05; RA-group, 3.42+/-1.48% to 5.46+/-1.79%, P<0.05),
      while there were no differences in NMD. The effects on lipid profiles were
      identical in the two groups. In addition, FMD improvement was greater in the RA
      group than in the R-group (Deltachange 2.15+/-1.29% vs. 1.16+/-1.15%, P<0.05).
      CONCLUSION: Beta-blockade enhances the pleiotropic effects of statins on
      endothelial function. The mechanism should be confirmed by further studies.

PMID- 24452084
TI  - The level of complement C3 is associated with the severity of atherosclerosis but
      not with arterial calcification in peripheral artery disease.
AB  - AIM: Recent evidences show correlations between atherosclerosis and the serum
      level of third component of complement (C3). However, there is less data on the
      connection of C3 and the severity of atherosclerosis. The aim of our study was to
      evaluate the association of serum C3 levels with atherosclerosis and arterial
      calcification in patients with chronic lower extremity atherosclerosis. METHODS:
      In a single centre cross-sectional study 103 patients and 109 healthy controls
      were examined. Sera were analyzed for C3. To identify the severity of
      atherosclerosis and calcification, ankle-brachial Doppler index, angiographic
      Bollinger score, arterial calcification score and carotid intima-media thickness
      was determined. RESULTS: Serum level of C3 was significantly higher in the lower
      extremity atherosclerosis group than in healthy patients (P=0.00004). In the
      patient group, serum level of C3, C4 was significantly and inversely associated
      with ABI (r=-0.246, P=0.014), (r=-0.259, P=0.011). C3 inversely correlates with
      Bollinger score (r= -0.357, P=0.028). Among our patients no correlation was found
      between C3 levels and CS (P=0.672, r=-0.046) or between C3 levels and carotid IMT
      (r=0.104, P=0.351). The serum levels of different complement components were
      associated with C-reactive protein, Hba1c, peptide-C and insulin. CONCLUSION: Our
      results suggest that C3 serum levels are associated with ABI and angiographic
      parameters of atherosclerosis, but do not relate to the severity of
      calcification.

PMID- 24452085
TI  - Electrical calf muscle stimulation with Veinoplus device in postoperative venous
      thromboembolism prevention.
AB  - AIM: The aim of this pilot study was to evaluate the potential effect of
      electrical calf muscle stimulation (EMS) in the prevention of postoperative deep
      vein thrombosis (DVT) in high risk patients and to assess efficacy and safety of
      EMS in patients with calf DVT. METHODS: This was a prospective non-randomized
      controlled study involving 80 patients over the age of 40 having major surgery
      (44 abdominal and 36 cranial or spinal surgery; duration more than 60 min under
      general anesthesia). Patients were divided into 2 comparable groups: main (N.=40)
      and control (N.=40). In both groups graduated middle stretch compression bandage
      with compression level 20-40 mmHg was applied and low dose unfractioned heparin
      (LDUH) injections (5000 U s.c. 3 t.i.d) were started on 1st or 2-5th day after
      surgery and continued until discharge. The time of starting LDUH was comparable
      in both groups. In addition, electrical calf muscle stimulation (EMS) with
      Veinoplus device was performed for not less than 5 periods of 20 minutes per day
      (total >100 minutes) in the main group. Control of venous patency was performed
      with duplex ultrasound obligatory at baseline (first 24 h after surgery) and then
      every 3 days until discharge. RESULTS: The incidence of DVT was 2.5% in the main
      group and 25% in the control group (P=0.007). In patients without DVT at baseline
      it was 3% versus 21% (P=0.025). Patients with baseline thrombosis who underwent
      EMS did not have any new cases of DVT and PE, while in patients without EMS
      thrombosis progression was observed in 43% cases also without pulmonary embolism
      (not significant). CONCLUSION: EMS with Veinoplus device at >100 min per day (>5
      sessions) can decrease the rate of postoperative DVT in high risk patients. Using
      of EMS in patients with calf DVT does not increase the rate of PE. These findings
      need to be confirmed in a randomized controlled trial.

PMID- 24452086
TI  - Usefulness of automatic measurement of contrast flow intensity: an innovative
      tool in contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque
      neovascularization. A pilot study.
AB  - AIM: Contrast-enhanced ultrasound imaging of the carotid arteries (CECU) permits
      direct, real-time visualization of neovascularization in atherosclerotic plaques
      and is a confirmed predictor of unstable atheromatous lesions. The aim of the
      study was the assessment of a new, automatically measured index of intensity in
      quantitative estimation of the contrast flow through the carotid plaque (till now
      assessed only visually). METHODS: Forty-four patients (mean age 70.4+/-11.4) with
      ultrasound diagnosed significant stenosis of internal carotid artery (ICA), after
      cerebrovascular or cardiovascular events, qualified for carotid artery stenting
      (CAS) were examined. The carotid ultrasound examinations with contrast agent
      Sonovue were performed. RESULTS: Visually in 22 patients (50%) contrast flow
      through the atherosclerotic plaques was found. In 17 patients (38.6%) massive,
      calcified atherosclerotic plaques were present. Patients with preserved contrast
      flow through the plaque more frequently had a history of cerebral stroke
      (P=0.04). Massive calcifications of atherosclerotic plaques correlated with a
      previous MI (P=0.03) and the degree of advancement of coronary artery disease
      (P=0.04), but not with a previous cerebral stroke. Contrast flow through the
      atherosclerotic plaque positively correlated with values of the index of
      intensity (r=0.69, P<0.00001). In patients with preserved contrast flow the mean
      value of the index of intensity was 22.24+/-3.55 dB as compared with 12.37+/-7.67
      dB - a value present in patients without preserved contrast flow. No significant
      relation for the degree of calcifications and the value of the index of intensity
      was found. CONCLUSION: The assessment of the index of intensity is a novel,
      simple and automatic method to estimate the degree of contrast flow through the
      carotid plaque. The values of the index of intensity correlate with the contrast
      flow through the atherosclerotic plaque, but not with its calcification.

PMID- 24452087
TI  - Socioeconomic characteristics of patients undergoing ambulatory diagnostic
      cerebral angiography in four US States.
AB  - AIMS: Several groups have demonstrated the safety of ambulatory cerebral
      angiography, with no patients experiencing complications related to early
      discharge. Although this practice appears to be safe, the socioeconomic
      characteristics factoring in the selection of the patients have not been
      investigated. METHODS: We performed a retrospective cohort study involving 45,226
      patients undergoing outpatient and 159,046 undergoing inpatient cerebral
      angiography, who were registered in the State Ambulatory Surgery Databases (SASD)
      and State Inpatient Databases (SID) respectively for 4 US States (New York,
      California, Florida, North Carolina). RESULTS: In a multivariate analysis of
      diagnostic cerebral angiography, Caucasian race (OR 1.36, 95% CI, 1.31, 1.42) and
      male gender (OR 1.36, 95% CI, 1.31, 1.41), were significantly associated with
      outpatient procedures. Higher Charlson Comorbidity Index (CCI) (OR 0.60, 95% CI,
      0.54, 0.67), high income (OR 0.70, 95% CI, 0.67, 0.73), high volume hospitals (OR
      0.69, 95% CI, 0.66, 0.73), and coverage by Medicare/Medicaid (OR 0.96, 95% CI,
      0.92, 0.99) were associated with a decreased chance of outpatient procedures.
      Institutional charges were significantly less for outpatient cerebral
      angiography. The median charge for inpatient diagnostic cerebral angiography was
      $26,968 as compared to $16,151 in the outpatient setting (P < 0.0001, Student's t
      test). CONCLUSION: Access to ambulatory diagnostic cerebral angiography appears
      to be more common for patients with private insurance and less comorbidities, in
      the setting of lower volume hospitals. Further investigation is needed in the
      direction of mapping these disparities in resource utilization.

PMID- 24452088
TI  - Incidence and related factors of upper gastrointestinal bleeding in a Chinese
      population of peripheral arterial disease during a six-year follow-up.
AB  - AIM: The aim of the study was to investigate the incidence and related factors of
      upper gastrointestinal bleeding (UGIB) in a Chinese population of peripheral
      arterial disease (PAD). METHODS: A total of 850 Chinese PAD patients were
      followed up for about 6 years. The incidence of UGIB was recorded and related
      factors were evaluated RESULTS: A total of 749 PAD patients with complete data
      were included in the final statistical analysis during the median follow-up time
      of 69 months. The incidence of UGIB in this PAD population was 8.4% during the
      follow-up. Univariate analysis indicated that PAD patients with UGIB were older.
      A higher percentage of patients with UGIB had hypertension, CKD, history of PUD,
      and used aspirin or warfarin than those without UGIB. But a lower percentage of
      patients with UGIB used PPI. The Cox regression analysis suggested that older age
      (HR: 1.035, 95% CI: 1.007-1.064), comorbidities of CKD (HR: 2.410, 95% CI: 1.455
      3.993), history of PUD (HR: 2.127, 95% CI: 1.102-4.100), use of aspirin (HR:
      1.517, 95% CI: 1.029-2.235) or warfarin (HR: 1.576, 95% CI: 1.002-2.252) were
      correlated with the higher incidence of UGIB in PAD patients during follow-up.
      Nevertheless, PPI use (HR: 0.612, 95% CI: 0.392-0.957) was correlated with the
      lower incidence of UGIB. CONCLUSION: There was a high incidence of UGIB in this
      Chinese population of PAD. Various factors including older age, comorbidities of
      CKD, history of PUD, use of aspirin or warfarin were correlated with the higher
      incidence of UGIB. PPI use was able to reduce the incidence of UGIB.

PMID- 24452089
TI  - Unfavorable results following surgical, endovascular and dermal treatments of
      vascular anomalies.
AB  - AIM: The aim of this paper to summarize the clinical characteristics of
      unfavorable results occurred following an unsuitable surgical, endovascular or
      dermal treatment for vascular anomalies. METHODS: Seventeen patients with
      vascular anomalies who had unintentional results following an intervention that
      was not consistent with the one suggested by a local academic multidisciplinary
      team were enrolled. The medical records of all patients were retrospectively
      examined. RESULTS: Venous malformation was the most frequent lesion in the
      patients (41.2%). More than half of the patients (52.9%) had an inadequate
      treatment as a concomitant of lack of a correct diagnosis. The most frequently
      occurred unfavorable result was the progression of the disease, the recurrence of
      the lesions, and clinical deterioration (64.7%). CONCLUSION: The physicians who
      participating in the management of vascular anomalies should have a higher order
      of qualification than an average degree. Also, a multidisciplinary approach for
      the management of these anomalies is recommended.

PMID- 24452090
TI  - The effect of aliskiren versus ramipril-based treatment on the Ambulatory
      Arterial Stiffness Index in hypertensive patients.
AB  - AIM: Aim of the present study was to compare the effectiveness of two renin
      angiotensin-aldosterone system inhibitors in arterial stiffness reduction in
      previously untreated hypertensive patients. METHODS: In this open label study,
      154 naive, or not treated in the last six months hypertensive patients were
      randomly assigned to receive aliskiren 300 mg or ramipril 5 mg daily. Six weeks
      after the initiation of treatment, patients were evaluated for blood pressure
      (BP) control. Patients with SBP >=140 and/or DBP >=90 mmHg were assigned to an
      adjunct of 25 mg hydrochlorothiazide as combination treatment. A re-evaluation of
      BP control was done after another 6 weeks. Individuals with BP >=140/90 mmHg were
      further administered amlodipine 5 mg. The final evaluation was performed six
      months after the start of the study. Twenty four-hour ambulatory blood pressure
      monitoring was carried out and the ambulatory arterial stiffness index (AASI) was
      calculated at baseline and after 6 months of treatment. RESULTS: Aliskiren-based
      therapy, as compared with ramipril-based therapy reduced BP to a similar degree:
      13+/-11 vs. 12+/-11 mmHg reduction in systolic (P=0.34) and 8+/-7 vs. 7+/-7 mmHg
      reduction in diastolic BP (P=0.44). AASI was reduced by 0.04+/-0.1 in the
      aliskiren group and by 0.02+/-0.2 in the ramipril group. AASI reduction did not
      differ significantly in the two groups (P=0.13). CONCLUSION: In hypertensive
      patients, aliskiren-based treatment as well as ramipril-based treatment appears
      to have a beneficial effect on arterial stiffness. As arterial stiffness is an
      important modifiable risk factor, our findings highlight the value of aliskiren
      beyond BP lowering properties.

PMID- 24452091
TI  - Varicose veins, there is more than meets the eye.

PMID- 24452092
TI  - Alexander Schirger.

PMID- 24452093
TI  - Production of reactive oxygen and nitrogen species by light irradiation of a
      nitrosyl phthalocyanine ruthenium complex as a strategy for cancer treatment.
AB  - Production of reactive oxygen species has been used in clinical therapy for
      cancer treatment in a technique known as Photodynamic Therapy (PDT). The success
      of this therapy depends on oxygen concentration since hypoxia limits the
      formation of reactive oxygen species with consequent clinical failure of PDT.
      Herein, a possible synergistic effect between singlet oxygen and nitric oxide
      (NO) is examined since this scenario may display increased tumoricidal activity.
      To this end, the trinuclear species [Ru(pc)(pz)2{Ru(bpy)2(NO)}2](PF6)6 (pc =
      phthalocyanine; pz = pyrazine; bpy = bipyridine) was synthesized to be a combined
      NO and singlet oxygen photogenerator. Photobiological assays using at 4 * 10(-6)
      M in the B16F10 cell line result in the decrease of cell viability to 21.78 +/-
      0.29% of normal under light irradiation at 660 nm. However, in the dark and at
      the same concentration of compound , viability was 91.82 +/- 0.37% of normal. The
      potential application of a system like in clinical therapy against cancer may be
      as an upgrade to normal photodynamic therapy. 

PMID- 24452095
TI  - The acceleration of boron neutron capture therapy using multi-linked
      mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide.
AB  - New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the
      nuclear reaction of boron-10 with neutron irradiation. The median survival of
      BNCT patients with glioblastoma was almost twice as long as those receiving
      standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two
      boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were
      used for BNCT. BPA is taken up into cells through amino acid transporters that
      are expressed highly in almost all malignant cells, but BSH cannot pass through
      the cell membrane and remains outside the cell. We simulated the energy transfer
      against the nucleus at different locations of boron from outside the cell to the
      nuclear region with neutron irradiation and concluded that there was a marked
      difference between inside and outside the cell in boron localization. To overcome
      this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for
      transduction of BSH. CPP (cell-membrane penetrating peptide) is very common
      peptide domains that transduce many physiologically active substances into cells
      in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize
      inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH
      fused to 11R with a dendritic lysine structure was synthesized and administrated
      to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at
      the cell nucleus and showed a very high boron value in ICP results. With neutron
      irradiation, the 8BSH-11R administrated group showed a significant cancer killing
      effect compared to the 100 times higher concentration of BSH-administrated group.
      We concluded that BSH-fused CPPs were one of the most improved and potential
      boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the
      clinical setting.

PMID- 24452096
TI  - Intramolecular electron transfer between molybdenum and iron mimicking bacterial
      sulphite dehydrogenase.
AB  - Diferrocenyl/diferrocenium substituted dioxido molybdenum(VI) complexes [Fe2MoO2]
      2(Fc)/[2(FC)]2+ mimic the catalytic active site including the redox subunits as
      well as the catalytic function of bacterial sulphite oxidases.

PMID- 24452097
TI  - Enantioselective lactic acid production by an Enterococcus faecium strain showing
      potential in agro-industrial waste bioconversion: physiological and proteomic
      studies.
AB  - The growing demand of biodegradable plastic polymers is increasing the industrial
      need of enantiospecific l-lactic acid (l-LA), the building block to produce
      polylactides. The most suitable industrial strategy to obtain high amounts of LA
      is the microbial fermentation of fruit and vegetable wastes by lactic acid
      bacteria (LAB). In this paper seven LAB strains from our laboratory collection,
      were screened for their ability to produce the highest amount of pure l-LA. A
      strain of Enterococcus faecium (LLAA-1) was selected and retained for further
      investigations. E. faecium LLAA-1 was grown in different culture media
      supplemented with the most abundant sugars present in agricultural wastes (i.e.,
      glucose, fructose, cellobiose and xylose) and its ability to metabolize them to l
      LA was evaluated. All tested sugars proved to be good carbon sources for the
      selected strain, except for xylose, which resulted in unsatisfactory biomass and
      LA production. Growth under aerobic conditions further stimulated l-LA production
      in fructose supplemented cultures with respect to anoxic-grown cultures.
      Proteomic profiles of E. faecium LLAA-1 grown in aerobiosis and anoxia were
      compared by means of two-dimensional electrophoresis followed by MALDI-TOF mass
      spectrometry. Seventeen proteins belonging to three main functional groups were
      differentially expressed: the biosynthesis of 6 proteins was up-regulated in
      aerobic-grown cultures while 11 proteins were biosynthesized in higher amounts in
      anoxia. The de novo biosynthesis of the f-subunit of alkyl hydroperoxide
      reductase involved in the re-oxidation of NADH seems the key element of the
      global re-arrangement of E. faecium LLAA-1 metabolism under aerobic conditions.
      An improved oxidative catabolism of proteinaceous substrates (i.e., protein
      hydrolisates) seems the main phenomenon allowing both higher biomass growth and
      improved LA production under these conditions. 

PMID- 24452098
TI  - On-line near infrared bioreactor monitoring of cell density and concentrations of
      glucose and lactate during insect cell cultivation.
AB  - Near infrared spectroscopy is demonstrated as a suitable method for monitoring
      real time cell density and concentrations of glucose and lactate during insect
      cell cultivation. The utility of this approach is illustrated during the
      cultivation of Trichoplusia ni BTI-Tn-5B1-4 insect cells in a stirred-tank
      bioreactor. On-line near infrared measurements are made by passing unaltered
      culture medium through an autoclavable near infrared flow-through sample cell
      during the cultivation process. Single-beam near infrared spectra were collected
      over the combination spectral range (5000-4000cm(-1)) through a 1.5mm path length
      sample. Cell density calibration model was established by uni-variable linear
      regressions with measured mean absorbance values of on-line spectra collected
      during a cultivation run. Calibration models are generated for glucose and
      lactate by regression analysis of both off line and on line spectra collected
      during a series of pre-measurement cultivation runs. Analyte-specific calibration
      models are generated by using a combination of spectra from both natural,
      unaltered samples and samples spiked with known levels of glucose and lactate.
      Spiked samples are used to destroy concentration correlations between solutes,
      thereby enhancing the selectivity of the calibration models. Absorbance spectra
      are used to build partial least squares calibration models for glucose and
      lactate. The calibration model for cell density corresponds to a univariate
      linear regression calibration model based on the mean absorbance between 4750 and
      4250cm(-1). The standard errors of prediction are 1.54mM, 0.83mM, and
      0.38*10(6)cells/mL for the glucose, lactate, and cell density models,
      respectively. 

PMID- 24452099
TI  - Expression of green fluorescent protein in the chicken using in vivo transfection
      of the piggyBac transposon.
AB  - The chicken is a well-established model system for studying developmental biology
      and is recognized as one of the top food production animals in the world. For
      this reason the chicken is an excellent candidate for transgenic applications, as
      the technology can be applied to both areas of research. Transgenic technology
      has not been broadly utilized in the chicken model, however, primarily due to
      difficulties in targeting germ cells and establishing germ line transmission.
      Transgenic technologies using non-replicating viral particles have been used in
      the chick, but are unsuitable for many applications because of size and sequence
      restraints and low efficiency. To create a more versatile method to target chick
      germ line stem cells, we utilized the transposable element system piggyBac paired
      with an in vivo transfection reagent, JetPEI. piggyBac has been previously shown
      to be highly active in mammalian cells and will transpose into the chicken
      genome. Here, we show that JetPEI can transfect multiple chick cell types, most
      notably germline stem cells. We also show that pairing these two reagents is a
      viable and reproducible method for long-term expression of a transgene in the
      chicken. Stable expression of the green fluorescent protein (GFP) transgene was
      seen in multiple tissue types including heart, brain, liver, intestine, kidney
      and gonad. Combining an in vivo transfection strategy with the PB system provides
      a simple and flexible method for efficiently producing stable chimeric birds and
      could be used for production of germ line transgenics. 

PMID- 24452100
TI  - Rewiring global regulator cAMP receptor protein (CRP) to improve E. coli
      tolerance towards low pH.
AB  - Bioprocesses such as production of organic acids or acid hydrolysis of
      bioresources during biofuel production often suffer limitations due to microbial
      sensitivity under acidic conditions. Approaches for improving the acid tolerance
      of these microbes have mainly focused on using metabolic engineering tools. Here,
      we tried to improve strain acidic tolerance from its transcription level, i.e. we
      adopted error-prone PCR method to engineer global regulator cAMP receptor protein
      (CRP) of Escherichia coli to improve its performance at low pH. The best mutant
      AcM1 was identified from random mutagenesis libraries based on its growth
      performance. AcM1 almost doubled (0.113h(-1)) the growth rate of the control
      (0.062h(-1)) at pH 4.24. It also demonstrated better thermotolerance than the
      control at 48 degrees C, whose growth was completely inhibited at this
      temperature. Quantitative real time reverse transcription PCR results revealed a
      stress response overlap among low pH stress-, oxidative stress- and osmotic
      stress-related genes. The chief enzyme responsible for cell acid tolerance,
      glutamate decarboxylase, demonstrated over twofold activity in AcM1 compared to
      the control. Differential binding properties of AcM1 mutant CRP with Class-I, II,
      and III CRP-dependent promoters suggested that modifications to native CRP may
      lead to transcription profile changes. Hence, we believe that transcriptional
      engineering of global regulator CRP can provide a new strain engineering
      alternative for E. coli. 

PMID- 24452101
TI  - A nickel hydroxide-coated 3D porous graphene hollow sphere framework as a high
      performance electrode material for supercapacitors.
AB  - A three-dimensional (3D) porous graphene hollow sphere (PGHS) framework has been
      fabricated via a hard template method and used to anchor alpha-Ni(OH)2
      nanoparticles with the size of about 4 nm through electrochemical deposition. It
      is found that a 3D PGHS framework can improve the capacitive performance of
      Ni(OH)2 effectively. In hybrid materials, alpha-Ni(OH)2 achieves the high
      specific capacitance of 2815 F g(-1) at a scan rate of 5 mV s(-1) and 1950 F g(
      1) even at 200 mV s(-1) with a capacitance retention of about 70%, indicating
      that the alpha-Ni(OH)2-coated 3D PGHS framework exhibits high rate capability.
      The excellent performance of such hybrid material is believed to be due to the
      smaller size of Ni(OH)2 nanoparticles and the PGHS framework with large specific
      surface area promoting efficient electron transport and facilitating the
      electrolyte ions migration. These impressive results suggest that the composite
      is a promising electrode material for an efficient supercapacitor. 

PMID- 24452102
TI  - Nonadherence in chronic obstructive pulmonary disease patients: what do we know
      and what should we do next?
AB  - PURPOSE OF REVIEW: Although nonadherence research in patients with chronic
      obstructive pulmonary disease (COPD) lags well behind other diseases, new
      evidence helps inform understanding about the degree and underlying causes of
      patient nonadherence, interventions that can improve adherence, and areas of
      research needed to further progress in improving this problem in patients with
      COPD. RECENT FINDINGS: Fewer than half of treatments for COPD, including oxygen
      supplementation, physical rehabilitation, and medication, are taken as
      prescribed. Most patients abandon their treatment after an initial start.
      Nonadherence in turn contributes to rising rates of hospitalization, death, and
      healthcare costs. The reasons why patients choose not to use their COPD
      treatments are not fully understood, although depression is clearly a
      contributing factor. Although a substantial number of studies have tested
      adherence interventions, few have included COPD patients or addressed
      polypharmacy in patients with multiple comorbidities. SUMMARY: The paucity of
      research does not reflect the inadequacy of available treatments. Lessons learned
      from the research outside of COPD and a small number of COPD studies suggest that
      a collaborative care approach will likely provide the most potential for
      improving overall care, including management of depression and enhancement of
      adherence. Exploitation of mobile telephone technology to engage patients in a
      discussion of their self-care should not be ignored as a potential intervention
      for COPD patients. VIDEO ABSTRACT: 

PMID- 24452103
TI  - Man-made mineral fibers and interstitial lung diseases.
AB  - PURPOSE OF REVIEW: Manufactured (artificial) fibers represent an important and
      continuously growing volume among substitutes to natural fibers. A major
      proportion of the population in an industrialized society has been, is, or will
      be in contact with these fibers. The fibrous configuration of asbestos is well
      recognized as being an important parameter in toxicity, and now that of synthetic
      fibers is also suspected of inducing serious health effects on the respiratory
      system. There is an ongoing debate about the actual fibrogenic effect of these
      man-made mineral fibers (MMMFs) in humans. RECENT FINDINGS: Several case reports
      have demonstrated the biopersistance of MMMFs in the lung of workers who were
      exposed to rock wool or fiberglass for long periods of time and were diagnosed
      with interstitial pulmonary fibrosis. A 20-year follow up also identified
      refractory ceramic fibers in workers' lung tissue, with significant association
      between cumulative fiber exposure and radiographic pleural changes. Newly
      emerging man-made fiber industries appear to induce new types of occupational
      diseases. SUMMARY: Exposure of workers in MMMFs production plants is correlated
      to high risk for developing pneumoconiosis. Large epidemiological studies are
      needed in order to determine dose metrics for risk assessment and management.
      VIDEO ABSTRACT: 

PMID- 24452104
TI  - Further limiting bisphenol a in food uses could provide health and economic
      benefits.
AB  - There is mounting evidence that bisphenol A (BPA), a chemical used in the
      production of polycarbonate plastics and the linings of aluminum cans, may have
      adverse health consequences. The Food and Drug Administration has banned BPA from
      baby bottles and sippy cups but has deferred further action on other food uses
      that is, uses in metal-based food and beverage containers. This article
      quantifies the potential social costs of childhood obesity and adult coronary
      heart disease attributable to BPA exposure in the United States in 2008 and
      models the potential health and economic benefits associated with replacing BPA
      in all food uses. BPA exposure was estimated to be associated with 12,404 cases
      of childhood obesity and 33,863 cases of newly incident coronary heart disease,
      with estimated social costs of $2.98 billion in 2008. Removing BPA from food uses
      might prevent 6,236 cases of childhood obesity and 22,350 cases of newly incident
      coronary heart disease per year, with potential annual economic benefits of $1.74
      billion (sensitivity analysis: $889 million-$13.8 billion per year). Although
      more data are needed, these potentially large health and economic benefits could
      outweigh the costs of using a safer substitute for BPA.

PMID- 24452105
TI  - Epigenetic silencing of Na,K-ATPase beta 1 subunit gene ATP1B1 by methylation in
      clear cell renal cell carcinoma.
AB  - The Na,K-ATPase or sodium pump carries out the coupled extrusion of Na(+) and
      uptake of K(+) across the plasma membranes of cells of most higher eukaryotes. We
      have shown earlier that Na,K-ATPase-beta 1 (NaK-beta) protein levels are highly
      reduced in poorly differentiated kidney carcinoma cells in culture and in
      patients' tumor samples. The mechanism(s) regulating the expression of NaK-beta
      in tumor tissues has yet to be explored. We hypothesized that DNA methylation
      plays a role in silencing the NaK-beta gene (ATP1B1) expression in kidney
      cancers. In this study, to the best of our knowledge we provide the first
      evidence that ATP1B1 is epigenetically silenced by promoter methylation in both
      renal cell carcinoma (RCC) patients' tissues and cell lines. We also show that
      knockdown of the von Hippel-Lindau (VHL) tumor suppressor gene in RCC cell lines
      results in enhanced ATP1B1 promoter AT hypermethylation, which is accompanied by
      reduced expression of NaK-beta. Furthermore, treatment with 5-Aza-2'
      deoxycytidine rescued the expression of ATP1B1 mRNA as well as NaK-beta protein
      in these cells. These data demonstrate that promoter hypermethylation is
      associated with reduced NaK-beta expression, which might contribute to RCC
      initiation and/or disease progression. 

PMID- 24452106
TI  - X-ray phase-contrast imaging of the breast--advances towards clinical
      implementation.
AB  - Breast cancer constitutes about one-quarter of all cancers and is the leading
      cause of cancer death in women. To reduce breast cancer mortality, mammographic
      screening programmes have been implemented in many Western countries. However,
      these programmes remain controversial because of the associated radiation
      exposure and the need for improvement in terms of diagnostic accuracy. Phase
      contrast imaging is a new X-ray-based technology that has been shown to provide
      enhanced soft-tissue contrast and improved visualization of cancerous structures.
      Furthermore, there is some indication that these improvements of image quality
      can be maintained at reduced radiation doses. Thus, X-ray phase-contrast
      mammography may significantly contribute to advancements in early breast cancer
      diagnosis. Feasibility studies of X-ray phase-contrast breast CT have provided
      images that allow resolution of the fine structure of tissue that can otherwise
      only be obtained by histology. This implies that X-ray phase-contrast imaging may
      also lead to the development of entirely new (micro-) radiological applications.
      This review provides a brief overview of the physical characteristics of this new
      technology and describes recent developments towards clinical implementation of X
      ray phase-contrast imaging of the breast. 

PMID- 24452107
TI  - Assessment of coincidence and defect sizes in Bankart and Hill-Sachs lesions
      after anterior shoulder dislocation: a radiological study.
AB  - OBJECTIVE: Bankart and Hill-Sachs lesions are often associated with anterior
      shoulder dislocation. The MRI technique is sensitive in diagnosing both injuries.
      The aim of this study was to investigate Bankart and Hill-Sachs lesions with MRI
      to determine the correlation in occurrence and defect sizes of these lesions.
      METHODS: Between 2006 and 2013, 446 patients were diagnosed with an anterior
      shoulder dislocation and 105 of these patients were eligible for inclusion in the
      study. All patients were examined using MRI. Bankart lesions were classified as
      cartilaginous or bony lesions. Hill-Sachs lesions were graded I-III using a
      modified Calandra classification. RESULTS: The co-occurrence of injuries was high
      [odds ratio (OR) = 11.47; 95% confidence interval (CI) = 3.60-36.52; p < 0.001].
      Patients older than 29 years more often presented with a bilateral injury (OR =
      16.29; 95% CI = 2.71-97.73; p = 0.002). A correlation between a Bankart lesion
      and the grade of a Hill-Sachs lesion was found (rho = 0.34; 95% CI = 0.16-0.49; p
      < 0.001). Bankart lesions co-occurred more often with large Hill-Sachs lesions (O
      = 1.24; 95% CI = 1.02-1.52; p = 0.033). CONCLUSION: If either lesion is
      diagnosed, the patient is 11 times more likely to have suffered the associated
      injury. The size of a Hill-Sachs lesion determines the co-occurrence of
      cartilaginous or bony Bankart lesions. Age plays a role in determining the type
      of Bankart lesion as well as the co-occurrence of Bankart and Hill-Sachs lesions.
      ADVANCES IN KNOWLEDGE: This study is the first to demonstrate the use of high
      quality MRI in a reasonably large sample of patients, a positive correlation of
      Bankart and Hill-Sachs lesions in anterior shoulder dislocations and an
      association between the defect sizes.

PMID- 24452108
TI  - Composite risk scores and composite endpoints in the risk prediction of outcomes
      in anticoagulated patients with atrial fibrillation. The Loire Valley Atrial
      Fibrillation Project.
AB  - Several validated risk stratification schemes for prediction of ischaemic stroke
      (IS)/thromboembolism (TE) and major bleeding are available for patients with non
      valvular atrial fibrillation (NVAF). On the basis for multiple common risk
      factors for IS/TE and bleeding, it has been suggested that composite risk
      prediction scores may be more practical and user-friendly than separate scores
      for bleeding and IS/TE. In a long-term prospective hospital registry of
      anticoagulated patients with newly diagnosed AF, we compared the predictive value
      of existing risk prediction scores as well as composite risk scores, and also
      compared these risk scoring systems using composite endpoints. Endpoint 1 was the
      simple composite of IS and major bleeds. Endpoint 2 was based on a composite of
      IS plus intracerebral haemorrhage (ICH). Endpoint 3 was based on weighted
      coefficients for IS/TE and ICH. Endpoint 4 was a composite of stroke,
      cardiovascular death, TE and major bleeding. The incremental predictive value of
      these scores over CHADS2 (as reference) for composite endpoints was assessed
      using c-statistic, net reclassification improvement (NRI) and integrated
      discrimination improvement (IDI). Of 8,962 eligible individuals, 3,607 (40.2%)
      had NVAF and were on OAC at baseline. There were no statistically significant
      differences between the c-statistics of the various risk scores, compared with
      the CHADS2 score, regardless of the endpoint. For the various risk scores and
      various endpoints, NRI and IDI did not show significant improvement (>=1%),
      compared with the CHADS2 score. In conclusion, composite risk scores did not
      significantly improve risk prediction of endpoints in patients with NVAF,
      regardless of how endpoints were defined. This would support individualised
      prediction of IS/TE and bleeding separately using different separate risk
      prediction tools, and not the use of composite scores or endpoints for everyday
      'real world' clinical practice, to guide decisions on thromboprophylaxis. 

PMID- 24452110
TI  - Cardio-ankle velocity index(CAVI) contributes to coronary artery disease risk
      prediction.

PMID- 24452111
TI  - Trends in the incidence and mortality of coronary heart disease in asian pacific
      region: the Singapore experience.
AB  - The rates of coronary heart disease are lower in Asia than in developed
      countries. Singapore has undergone rapid urbanization over the past several
      decades. In the several decades between the 1960s and 1980s, a rapid increase in
      the rates of ischemic heart disease was observed, to the extent that Singapore
      exhibits one of the highest rates of mortality from cardiovascular disease in the
      Asia-Pacific region, higher even than the rates in North America. Rates of
      cardiovascular disease have now stabilized, and are declining. This is, a pattern
      that has been observed in many developed countries. Increased life expectancy has
      resulted in an epidemiologic transition that has seen chronic non-communicable
      diseases replace malnutrition and infections as the major causes of mortality. At
      the same time, there have been changes in nutrient intake and physical activity
      as well as rapid increases in the levels of several cardiovascular risk factors
      including obesity, hypertension, hyperlipidemia, diabetes mellitus and systemic
      inflammation. Furthermore, when present, there is a lack of awareness and sub
      optimal treatment of these risk factors. In addition to the changes in
      environmental exposures related to socio-economic development, it does appear
      that specific populations are particularly prone to the development of
      cardiovascular disease and its risk factors. In particular, Asian Indians
      experience a high rate of coronary heart disease and diabetes mellitus. Emerging
      data suggests that Chinese may be particularly prone to the adverse effects of
      obesity in relation to insulin resistance and inflammation. A concerted effort to
      change lifestyles to prevent the development of coronary heart disease risk
      factors, and to improve awareness and treatment of risk factors when then
      develop, is required to halt the epidemic of coronary heart disease that is
      occurring in Asia. 

PMID- 24452112
TI  - Gender disparities in optimal lipid control among patients with coronary artery
      disease.
AB  - Coronary heart disease(CHD) is the leading cause of death worldwide in both men
      and women. Hypercholesterolemia is a major factor contributing to the incidence
      of CHD. Many lipid-lowering trials have shown statins to be effective medications
      for the primary and secondary prevention of CHD. Some studies have suggested that
      statins are as or more effective in women than in men. However, there is a
      substantial gender gap in lipid goal attainment with respect to primary care
      guidelines, as reported in observational studies. In this article, we attempt to
      explain gender differences in lipid control in individuals with or at risk of CHD
      in order to improve awareness of and narrow gaps in gender disparities in lipid
      management. 

PMID- 24452115
TI  - Metabolic syndrome and cardiovascular diseases in Korea.
AB  - There has been a rapid increase in the prevalence of obesity, type 2 diabetes and
      metabolic syndrome(MetS) over the past two to three decades in most Asian
      countries. According to the Korean National Health and Nutrition Examination
      Survey(KNHANES), the prevalence of MetS significantly increased from 24.9% to
      31.3% between 1998 and 2007. The clinical significance of MetS is based on the
      increased risk for the development of cardiovascular disease(CVD). We analyzed
      the 8-year follow-up data of 2,435 healthy subjects and found that MetS was
      associated with an increased risk of CVD in both men and women(OR: 1.98, 95% CI:
      1.30-3.03 in men; OR: 4.04, 95% CI: 1.78-9.14 in women). MetS was significantly
      associated with the risk for future coronary heart disease(CHD) in men(OR: 3.68;
      95% CI: 1.93-7.01) and stroke in women(OR: 3.96; 95% CI: 1.58- 9.94). We also
      analyzed the echocardiographic findings of 1,600 healthy subjects to evaluate the
      relationship between metabolic syndrome and left ventricular diastolic
      dysfunction(LVDD). The patients with MetS exhibited significant differences in
      parameters of cardiac structure and the LV diastolic function compared to that
      observed in the patients without MetS. MetS was associated with an increased risk
      of LVDD(OR: 1.67; 95% CI: 1.18-2.37). These results suggest that the presence of
      MetS is associated with an increased risk for the development of serious CVD and
      abnormal changes in the LV structure and diastolic function, even before the
      development of overt CVD. 

PMID- 24452116
TI  - The risk factors of acute coronary syndrome in patients over 65 years old at
      Thong Nhat Hospital of Ho Chi Minh City, Vietnam.
AB  - BACKGROUND: Elderly patient group is increasing quickly. The same phenomenon is
      seen in Vietnam. The prevalence of coronary artery disease(CAD) also increases
      with age. This was seen at Thong Nhat hospital, where was a high proportion of
      elderly patients admitted with acute coronary syndrome(ACS). This is why there
      was a need for studies on the risk factors and prevention of ACS for the elderly
      patients in Vietnam. OBJECTIVES: We assess the prevalence of common risk factors
      in the elderly patients with ACS admitted to Thong Nhat hospital. METHOD OF
      STUDY: A retrospective cross-sectional descriptive study was conducted at Thong
      Nhat hospital in Ho Chi Minh city from 1/2009 to 1/2011, in which 338 patients
      with ACS were divided in two groups: 214 patients over 65 years(62 females and
      152 males) formed elderly group and 124 patients <= 65 years(21 females and 103
      males) formed non-elderly group. The cardiovascular risk factors of ACS were
      hypertension(HT), diabetes mellitus(DM), smoking, dyslipidemia and obesity(BMI >=
      23 kg/m(2)). A comparison of risk factors between the two group was done by Chi
      square. RESULTS: The number of female with was higher in the elderly group with
      ACS. Most of the elderly group had multiple risk factors. The percentage of 1, 2,
      3 and 4 risk factor were 3.3; 32.2; 41.1% and 23.4%, respectively and they were
      similar to non-elderly group. In the elderly group, the prevalence of HT and DM
      were 84.6% and 29.0% higher than that in the non elderly group; the prevalence of
      smoking and dyslipidemia were 22.0% and 56.9% lower than that in the non-elderly
      group. The prevalence of the elderly patients with angina pectoris was 41.1%
      higher than that in the nonelderly group but the prevalence of non-typical angina
      was 42.1% higher than that in the non-elderly group(16.1%). The prevalence of
      prior myocardial infarction in elderly group was 18.2%, while the prevalence of
      obesity was 35.8% similar to that of the non-elderly group. CONCLUSION: In
      elderly patients with ACS, multiple risk factors were common. The prevalence of
      HTN and DM was higher, smoking and dyslipidemia were lower, being overweight and
      having a prior myocardial infarction was similar to that of the non-elderly
      group.

PMID- 24452117
TI  - Socio-demographic factors and the prevalence of metabolic syndrome among
      filipinos from the LIFECARE cohort.
AB  - BACKGROUND: Metabolic syndrome(MetS) is an aggregation of multiple metabolic risk
      factors shown to lead to the development of cardiovascular disease. The
      International Diabetes Federation(IDF) and the modified National Cholesterol
      Education Program Adult Treatment Panel III(mNCEP) criteria are used in
      identifying MetS. This report will determine the prevalence of MetS and its
      component risk factors of the Philippine cohort of the LIFE course study in
      CARdiovascular disease Epidemiology(LIFECARE). METHODS: Our study recruited 3,072
      participants aged 20-50 years old from Metro Manila and four nearby provinces.
      Baseline anthropometric and clinical parameters were measured. Prevalence of MetS
      and its component factors were determined. Associations with socio-demographic
      factors were determined. RESULTS: The prevalence of MetS was 19.7% and 25.6% by
      IDF and mNCEP, respectively(kappa 0.83). Both were associated with increasing
      age, urban residence, and employed status. It was higher in females by IDF and in
      males by mNCEP. IDF missed 40% of males and 10% of females identified with MetS
      by mNCEP. More males were identified by the mNCEP as MetS despite relatively
      normal waist circumference. CONCLUSION: MetS is common in the Philippines among
      older, educated, and urban residents. The mNCEP criteria identified more MetS
      than the IDF criteria.

PMID- 24452118
TI  - Bringing microbial interactions to light using imaging mass spectrometry.
AB  - Covering: up to the end of September 2013 Microorganisms are a plentiful resource
      for natural products research. Traditionally, natural products discovery from
      microbial sources depends on the screening of target-mediated inhibition. The
      natural products identified through this strategy usually correlate to
      significant microbial phenotypes. However, the target-mediated transcriptions
      deduced from low concentrations of natural products sometimes do not generate an
      obvious phenotype. The better understanding of the true biological roles of those
      microbial natural products will permit the application of rational approaches to
      the more effective exploitation of their use. Imaging mass spectrometry (IMS) has
      been developed and applied in many fields for decades. However, the applications
      of IMS on microbial natural products research have just been recently reported.
      IMS is one of few tools capable of revealing both phenotype and relevant and
      irrelevant chemotypes of microorganisms. In this review, we summarize the latest
      applications of IMS technologies. The challenges and prospect of improvement and
      application of IMS to microbial natural products research are discussed as well.

PMID- 24452119
TI  - Wharton's Jelly human mesenchymal stem cell contact guidance by noisy
      nanotopographies.
AB  - The development of biomaterials ensuring proper cell adhesion, polarization,
      migration and differentiation represents a true enabler for successful tissue
      engineering applications. Surface nanostructuring was suggested as a promising
      method for improving cell-substrate interaction. Here, we study Wharton's Jelly
      human Mesenchymal Stem Cells (WJ-hMSC) interacting with nanogratings (NGs) having
      a controlled amount of nanotopographical noise (nTN). Our data demonstrate that
      unperturbed NGs induce cell polarization, alignment and migration along NG lines.
      The introduction of nTN dramatically modifies this behavior and leads to a marked
      loss of cell polarization and directional migration, even at low noise levels.
      High-resolution focal adhesions (FAs) imaging showed that this behavior is caused
      by the release of the geometrical vinculum imposed by the NGs to FA shaping and
      maturation. We argue that highly anisotropic nanopatterned scaffolds can be
      successfully exploited to drive stem cell migration in regenerative medicine
      protocols and discuss the impact of scaffold alterations or wear. 

PMID- 24452129
TI  - New lead-free piezoelectric ceramics based on (K0.48Na0.52)(Nb0.95Ta0.05)O3
      Bi0.5(Na0.7K0.2Li0.1)0.5ZrO3.
AB  - (1 - x)(K0.48Na0.52)(Nb0.95Ta0.05)O3-xBi0.5(Na0.7K0.2Li0.1)0.5ZrO3 lead-free
      piezoelectric ceramics with a new type of phase boundary have been designed and
      fabricated. This phase boundary lies in the compositional range of 0.04 <= x <=
      0.05, and is formed by the coexistence of the rhombohedral, orthorhombic, and
      tetragonal phases. Interestingly, we found that the ferroelectric, dielectric,
      and piezoelectric properties of the ceramics with compositions near the phase
      boundary are significantly enhanced. In particular, the ceramic with x = 0.045
      shows the best piezoelectric behavior of d33 ~ 290 pC/N and kp ~ 0.42 among all
      the compositions studied in this work, and it also exhibits a good thermal
      stability at annealing temperatures of <=270  degrees C. All these results
      indicate that such a material system is a good candidate for lead-free
      piezoelectric applications in the future. 

PMID- 24452130
TI  - HIF-1alpha silencing suppresses growth of lung adenocarcinoma A549 cells through
      induction of apoptosis.
AB  - Lung adenocarcinoma (AC) is one of the most deadly malignancies. The disease has
      a low five-year survival rate; therefore, the identification of novel therapeutic
      agents is required. This study aimed to investigate the effect of small
      interfering RNA (siRNA) targeting hypoxia-inducible factor 1alpha (HIF-1alpha) on
      the growth of AC A549 cells. A549 cells were transfected with various
      concentrations of HIF-1alpha or control siRNA, and the effect on HIF-1alpha
      expression was analyzed using quantitative polymerase chain reaction and western
      blot analysis. The effects of HIF-1alpha siRNA on growth inhibition and apoptosis
      were then assessed using standard methods. HIF-1alpha siRNA treatment
      significantly reduced HIF-1alpha mRNA and protein expression in A549 cells.
      Furthermore, the downregulation of HIF-1alpha expression inhibited the growth of
      A549 cells and induced apoptosis of A549 cells by upregulating caspase-3
      expression. The present in vitro study demonstrates that the downregulation of
      HIF-1alpha is capable of suppressing AC A549 cell growth, through the induction
      of apoptosis. This suggests that HIF-1alpha inhibition may represent a promising
      strategy for the treatment of AC.

PMID- 24452131
TI  - Binding behaviors of protein on spatially controlled poly[oligo(ethylene glycol)
      methacrylate] brushes grafted from mixed self-assembled monolayers on gold.
AB  - Binding behaviors of streptavidin were investigated with different lateral
      packing densities of biotin-functionalized, non-biofouling pOEGMA brushes,
      synthesized by surface-initiated polymerization from mixed SAMs with different
      mole fractions of the polymerization initiator on gold surfaces. 

PMID- 24452132
TI  - Fatal hemophagocytic lymphohistiocytosis associated with locally acquired dengue
      virus infection - New Mexico and Texas, 2012.
AB  - Dengue is caused by infection with any of four mosquito-transmitted dengue
      viruses (DENV-1-4) and is characterized by fever, headache, myalgia, and
      leukopenia. Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal
      hyperinflammatory syndrome that can be familial or acquired, and is characterized
      by persistent fever, pancytopenia, hepatosplenomegaly, and increased serum
      ferritin. Acquired HLH is most frequently associated with Epstein Barr virus
      infection but also has been associated with dengue. This report describes a fatal
      case of acquired HLH that was apparently triggered by infection with DENV-3. The
      patient developed an acute febrile illness in August 2012 during a 1-month
      vacation in New Mexico. After returning to her home in Texas, she was initially
      diagnosed with West Nile virus (WNV) infection, developed pancytopenia, liver
      failure, and disseminated intravascular coagulopathy, and died. DENV-3 was
      detected in a premortem bone marrow biopsy in which erythrophagocytosis was
      evident. This case underscores the need for clinicians in the United States to be
      vigilant for dengue and request diagnostic testing for suspected cases, which
      should be reported to public health authorities. 

PMID- 24452120
TI  - Regulation of mRNA transport, localization and translation in the nervous system
      of mammals (Review).
AB  - Post-transcriptional control of mRNA trafficking and metabolism plays a critical
      role in the actualization and fine tuning of the genetic program of cells, both
      in development and in differentiated tissues. Cis-acting signals, responsible for
      post-transcriptional regulation, reside in the RNA message itself, usually in
      untranslated regions, 5' or 3' to the coding sequence, and are recognized by
      trans-acting factors: RNA-binding proteins (RBPs) and/or non-coding RNAs
      (ncRNAs). ncRNAs bind short mRNA sequences usually present in the 3'-untranslated
      (3'-UTR) region of their target messages. RBPs recognize specific nucleotide
      sequences and/or secondary/tertiary structures. Most RBPs assemble on mRNA at the
      moment of transcription and shepherd it to its destination, somehow determining
      its final fate. Regulation of mRNA localization and metabolism has a particularly
      important role in the nervous system where local translation of pre-localized
      mRNAs has been implicated in developing axon and dendrite pathfinding, and in
      synapse formation. Moreover, activity-dependent mRNA trafficking and local
      translation may underlie long-lasting changes in synaptic efficacy, responsible
      for learning and memory. This review focuses on the role of RBPs in neuronal
      development and plasticity, as well as possible connections between ncRNAs and
      RBPs. 

PMID- 24452133
TI  - Prevalence and indicators of viral suppression among persons with diagnosed HIV
      infection retained in care - Georgia, 2010.
AB  - Advances in treatment have led to dramatic improvements in the health of persons
      infected with human immunodeficiency virus (HIV). Moreover, treatment can reduce
      HIV transmission because suppressed levels of circulating virus makes HIV
      infected persons less infectious. Until recently, antiretroviral therapy (ART)
      was recommended only for HIV patients with advanced disease (stages 2 and 3), and
      was optional for patients with early disease (stage 1). In March 2012, national
      HIV treatment guidelines were changed to recommend ART at all disease stages. To
      establish a baseline for care and treatment outcomes among persons with HIV, the
      Georgia Department of Public Health (DPH) examined whether viral suppression
      among HIV patients in Georgia varied by disease stage at diagnosis before
      implementation of the new guidelines. Disease stage at diagnosis was assessed as
      an indicator of viral suppression several months after diagnosis, adjusting for
      age, sex, and race/ethnicity among patients who were reported to DPH with HIV
      infections newly diagnosed during 2010 and retained in care. This report
      describes the results of that analysis, which indicated that disease stage at
      diagnosis was a significant indicator of viral suppression; viral suppression was
      significantly less frequent among persons with earlier disease stage at
      diagnosis. Compared with viral suppression among 80.5% of persons with stage 3
      HIV disease, only 72.3% with stage 2 disease (prevalence ratio [PR] = 0.9; 95%
      confidence interval [CI] = 0.8-1.0) and 64.5% with stage 1 disease (PR = 0.8; CI
      = 0.7-0.9) met criteria for viral suppression, likely resulting from lack of
      initiating treatment or inadequate adherence to treatment regimens, as suggested
      in previous studies. These data can serve as a baseline to determine the impact
      of the guideline change in the future, and can be used to emphasize the
      importance of implementing the guidelines by expanding treatment to persons at
      all disease stages to reach the goal of viral suppression for all persons with
      HIV, thus closing the gap in viral suppression among persons diagnosed at disease
      stages 1 and 2. Health-care providers and community-based organizations should
      inform patients of the recommendation for ART initiation at all disease stages. 

PMID- 24452134
TI  - Trends in uninsured clients visiting health centers funded by the Title X family
      planning program - Massachusetts, 2005-2012.
AB  - In 2006, Massachusetts passed legislation that broadened access to health
      insurance for its residents. The percentage of the state population that had
      health insurance (obtained through either private insurance or publicly funded
      programs) subsequently increased, reaching 97% in 2011, leaving only 3%
      uninsured, compared with approximately 9%-20% uninsured among nonelderly
      residents in 2006. Given such high rates of insurance coverage, questions arise
      about the need for categorical public health programs designed to serve clients
      without health insurance. This report describes trends in the percentage of
      uninsured clients seen at community-based organizations in Massachusetts that
      received federal funding for one such program, the Title X family planning
      program. Title X program data from 2005-2012 indicate that client volume remained
      high throughout the period, and that the percentage of clients who were uninsured
      declined, from 59% in 2005 to 36% in 2012. Across years, young adults aged 20-29
      years and persons whose incomes were 101%-250% of the federal poverty level were
      more likely to be uninsured than were persons in other age and income groups.
      After health-care reform, publicly funded family planning services in
      Massachusetts saw continued demand from uninsured and insured clients. Family
      planning services in other states implementing health-care reform might have a
      similar experience, and public health agencies are encouraged to track such
      trends to monitor the demand for such services and inform budget planning and
      resource allocation. 

PMID- 24452135
TI  - Notes from the field: Increase in reported legionellosis - Milwaukee, Wisconsin,
      June-September 2013.
AB  - In early July 2013, the City of Milwaukee Health Department (MHD) was notified by
      the Wisconsin Division of Public Health of an increase in reported cases of
      legionellosis in southeastern Wisconsin. Legionellosis is a reportable disease to
      state and local public health authorities in Wisconsin. During June 1-September
      30, 2013, a total of 58 clinically diagnosed cases of Legionnaires' disease,
      confirmed by laboratory testing, were reported in Milwaukee County, more than
      twice the number of total annual case reports in each of the previous 5 years.
      Forty-five (78%) of these cases were reported in the city of Milwaukee. The
      median age of county patients was 53 years (range = 29-77 years); all but one was
      hospitalized, and no deaths were reported. MHD received one report of a death
      attributed to legionellosis in the county during this period. 

PMID- 24452136
TI  - Density functional theory study on the activation of molecular oxygen on a
      stepped gold surface in an aqueous environment: a new approach for simulating
      reactions in solution.
AB  - The activation of oxygen molecules is an important issue in the gold-catalyzed
      partial oxidation of alcohols in aqueous solution. The complexity of the solution
      arising from a large number of solvent molecules makes it difficult to study the
      reaction in the system. In this work, O2 activation on an Au catalyst is
      investigated using an effective approach to estimate the reaction barriers in the
      presence of solvent. Our calculations show that O2 can be activated, undergoing
      OOH* in the presence of water molecules. The OOH* can readily be formed on
      Au(211) via four possible pathways with almost equivalent free energy barriers at
      the aqueous-solid interface: the direct or indirect activation of O2 by surface
      hydrogen or the hydrolysis of O2 following a Langmuir-Hinshelwood mechanism or an
      Eley-Rideal mechanism. Among them, the Eley-Rideal mechanism may be slightly more
      favorable due to the restriction of the low coverage of surface H on Au(211) in
      the other mechanisms. The results shed light on the importance of water molecules
      on the activation of oxygen in gold-catalyzed systems. Solvent is found to
      facilitate the oxygen activation process mainly by offering extra electrons and
      stabilizing the transition states. A correlation between the energy barrier and
      the negative charge of the reaction center is found. The activation barrier is
      substantially reduced by the aqueous environment, in which the first solvation
      shell plays the most important role in the barrier reduction. Our approach may be
      useful for estimating the reaction barriers in aqueous systems. 

PMID- 24452137
TI  - Mass spectrometry imaging of plant metabolites--principles and possibilities.
AB  - Covering: up to the end of 2013 New mass spectrometry imaging (MSI) techniques
      are gaining importance in the analysis of plant metabolite distributions, and
      significant technological improvements have been introduced in the past decade.
      This review provides an introduction to the different MSI techniques and their
      applications in plant science. The most common methods for sample preparation are
      described, and the review also features a comprehensive table of published
      studies in MSI of plant material. A number of significant works are highlighted
      for their contributions to advance the understanding of plant biology through
      applications of plant metabolite imaging. Particular attention is given to the
      possibility for imaging of surface metabolites since this is highly dependent on
      the methods and techniques which are applied in imaging studies.

PMID- 24452138
TI  - Integrating mental health and social development in theory and practice.
AB  - In many low and middle income countries, attention to mental illness remains
      compartmentalized and consigned as a matter for specialist policy. Despite great
      advances in global mental health, mental health policy and practice dovetail only
      to a limited degree with social development efforts. They often lag behind
      broader approaches to health and development. This gap ignores the small but
      growing evidence that social development unavoidably impacts the mental health of
      those affected, and that this influence can be both positive and negative. This
      article examines the theoretical and practical challenges that need to be
      overcome for a more effective integration of social development and mental health
      policy. From a theoretical perspective, this article demonstrates compatibility
      between social development and mental health paradigms. In particular, the
      capability approach is shown to provide a strong framework for integrating mental
      health and development. Yet, capability-oriented critiques on 'happiness' have
      recently been applied to mental health with potentially detrimental outcomes.
      With regard to policy and practice, horizontal and vertical integration
      strategies are suggested. Horizontal strategies require stronger devolution of
      mental health care to the primary care level, more unified messages regarding
      mental health care provision and the gradual expansion of mental health packages
      of care. Vertical integration refers to the alignment of mental health with
      related policy domains (particularly the social, economic and political domains).
      Evidence from mental health research reinforces aspects of social development
      theory in a way that can have tangible implications on practice. First, it
      encourages a focus on avoiding exclusion of those affected by or at risk of
      mental illness. Secondly, it underscores the importance of the process of
      implementation as an integral component of successful policies. Finally, by
      retaining a focus on the individual, it seeks to avoid uneven approaches to
      development. 

PMID- 24452139
TI  - The association of hospital cost-inefficiency with certificate-of-need
      regulation.
AB  - Certificate-of-need (CON) regulations can promote hospital efficiency by reducing
      duplication of services; however, there are practical and theoretical reasons why
      they might be ineffective, and the empirical evidence generated has been mixed.
      This study compares the cost-inefficiency of urban, acute care hospitals in
      states with CON regulations against those in states without CON requirements.
      Stochastic frontier analysis was performed on pooled time-series, cross-sectional
      data from 1,552 hospitals in 37 states for the period 2005 to 2009 with controls
      for variations in hospital product mix, quality, and patient burden of illness.
      Average estimated cost-inefficiency was less in CON states (8.10%) than in non
      CON states (12.46%). Results suggest that CON regulation may be an effective
      policy instrument in an era of a new medical arms race. However, broader analysis
      of the effects of CON regulation on efficiency, quality, access, prices, and
      innovation is needed before a policy recommendation can be made. 

PMID- 24452140
TI  - Surface glycoproteins of the recently identified African Henipavirus promote
      viral entry and cell fusion in a range of human, simian and bat cell lines.
AB  - The recent discovery of a wide range of henipavirus-like viruses circulating in
      Megabats in Africa raises the question as to the zoonotic potential of these
      pathogens given the high human mortality rates seen with their pathogenic
      relatives Nipah virus and Hendra virus. In the absence of cultured infectious
      African Henipavirus we have performed experiments with recombinant F and G
      glycoproteins from the representative African Henipavirus strain M74a aimed at
      estimating its cellular tropism and capacity to use similar receptors to its
      highly pathogenic counterparts. The ability of the M74a virus G surface protein
      to use the ubiquitous Ephrin B2 host cell receptor and its heterologous cross
      compatibility with Nipah virus could be expected to impart upon this virus a
      reasonable potential for species spillover, although differences in fusion
      efficiency seen with the M74a virus F protein in certain cell lines could present
      a barrier for zoonotic transmission. 

PMID- 24452141
TI  - Evolution of serotype A foot-and-mouth disease virus capsid under neutralizing
      antibody pressure in vitro.
AB  - In this study, the Indian foot-and-mouth disease virus (FMDV) vaccine strain (A
      IND 40/2000) was passaged under homologous bovine convalescent serum (BCS)
      pressure to gain insight into the evolutionary dynamics of the antigenic sites. A
      considerable drop in the neutralization titres of the BCS for the isolated
      variants as compared to the parental population in either virus neutralization or
      plaque reduction neutralization test was observed. T143K substitution preceding
      the integrin binding 'RGD'-motif in the betaG-betaH loop of VP1 was found to be
      selected consistently and exclusively under immune pressure. By virtue of its
      location within an immunodominant site, sequence heterogeneity observed in the
      field viruses and residues already mapped in the neutralizing monoclonal antibody
      resistant mutants, position 143 in VP1 was predicted to be a critical residue of
      an important neutralizing epitope in serotype A FMDV. Using next-generation
      sequencing approach, the gradual overtaking of the originally dominating major
      variant by a minor one under a selective environment could be demonstrated. In
      the control passage regimen, VP2 E131K substitution was fixed within the heparan
      sulfate binding pocket probably as a result of adaptation to use alternative
      cellular receptors. But at the same time, these substitutions arising under
      selection forces other than immune pressure changed the antigenic behaviour of
      the virus inadvertently. 

PMID- 24452142
TI  - Inhibition of the 26S proteasome as a possible mechanism for toxicity of heavy
      metal species.
AB  - In this paper we report on the synthesis of five metal complexes coordinated to
      the [NN'O] ligand HL(iodo) (2,4-diiodo-6-((pyridine-2
      ylmethylamino)methyl)phenol), namely [Al(III)(L(iodo))2]ClO4 (1),
      [Cd(II)(L(iodo))Cl].H2O (2), [Hg(II)(L(iodo))2].4DMSO (3), [Pb(II)(L(iodo))NO3]
      (4), and [Sn(IV)(L(iodo))Cl3] (5). Species 1-5 are thoroughly characterized by
      spectroscopic and spectrometric methods, as well as by elemental analysis. X-ray
      crystallography results for complex 3 indicate the presence of Hg(II) ion
      hexacoordinated to two facially oriented [NN'O] ligands, whereas for complex 5 an
      Sn(IV) ion chelates to one deprotonated ligand and three chlorido coligands. The
      toxicity of species 1-5 is tested against transformed human prostate epithelial
      cells CRL2221 and we observe that the five complexes demonstrate high levels of
      cell growth inhibition in a dose-dependent manner. In order to evaluate the
      relationship between these species and the proteasome, we test 1-5 against
      purified 20S, CRL2221 cell extracts, and intact cells, followed by the
      measurement of the percent chymotrypsin-like activity inhibition levels. Results
      suggest a good correlation between the toxicity of [Hg(II)(L(iodo))2].4DMSO (3)
      and proteasome inhibition. 

PMID- 24452143
TI  - Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors
      and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic
      Treatment.
AB  - In the present study we investigated the prognostic value of Circulating Tumour
      Cells (CTC) and their utility for therapy monitoring in non-small cell lung
      cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were
      prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th
      cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC
      related objects (not morphological standard or broken epithelial cells) were
      counted. At baseline 18 (41.9%) patients were positive for intact CTC count and
      10 (23.2%) of them had >=5 CTC, while CK positive events were found in 79.1% of
      patients. The group of patients with CTC 35 at baseline presented worse PFS and
      OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally,
      high levels of total CK positive events were associated with poor prognosis in
      the group of patients with <5 CTC. Regarding therapy monitoring, patients
      presenting increased levels of CTC during the treatment demonstrated lower OS and
      PFS rates. All these data supported the value of CTC as a prognostic biomarker
      and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC
      patients, with the additional value of analyzing other "objects" such as
      apoptotic CTC or CK fragments to guide the clinical management of these patients.

PMID- 24452144
TI  - Gene Expression Profiling Identifies Important Genes Affected by R2 Compound
      Disrupting FAK and P53 Complex.
AB  - Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role
      in many cellular processes: adhesion, proliferation, invasion, angiogenesis,
      metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl
      15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53
      proteins, activates p53 transcriptional activity, and blocks tumor growth. In
      this report we performed a microarray gene expression analysis of R2-treated
      HCT116 p53+/+ and p53-/- cells and detected 1484 genes that were significantly up
      or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53-/- cells.
      Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets:
      Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and
      other genes were identified. In addition, a combination of R2 compound with M13
      compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm
      2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more
      significantly than each agent alone in a p53-dependent manner. Thus, the report
      detects gene expression profile in response to R2 treatment and demonstrates that
      the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy
      approach. 

PMID- 24452145
TI  - [Picture in clinical hematology no. 68].

PMID- 24452146
TI  - [Outcome of patients with relapsed/refractory adult T-cell leukemia-lymphoma
      after salvage therapy].
AB  - We retrospectively analyzed 81 relapsed or refractory adult T-cell leukemia
      lymphoma (ATL) patients who received salvage therapy in our institution between
      2000 and 2010. These patients had received chemotherapy, radiation, or
      hematopoietic stem cell transplantation (HSCT) as an initial treatment, and were
      then given chemotherapy, radiation, HSCT, or donor lymphocyte infusion (DLI) as
      salvage therapy. Median survival time was 3.9 months. Of 5 long-term survivors,
      who survived more than 2 years after the first salvage therapy, 4 patients
      received HSCT or DLI, and the other was given mogamulizumab as the salvage
      therapy. For patients with relapsed or refractory ATL, HSCT/DLI is a promising
      treatment for achieving long-term survival. Mogamulizumab may be the good choice
      for those who are ineligible for HSCT. 

PMID- 24452147
TI  - [Acute monoblastic leukemia with MLL/AF9 rearrangement which developed 18 months
      after myeloid sarcoma onset].
AB  - We describe a 36-month-old boy with acute monoblastic leukemia (AMoL M5a) and
      mixed-lineage leukemia (MLL)-AF9 rearrangement. At 18 months of age, he presented
      with swelling on the back of his hand that was considered to be an inflammatory
      change, but no hematological abnormalities were found. However, blasts with MLL
      AF9 rearrangement were detected in biopsied tissue taken at the time and in
      peripheral blood samples taken 18 months later. These findings indicate that
      myeloid sarcoma with MLL-AF9 rearrangement may ultimately, though slowly,
      progress to AMoL. 

PMID- 24452148
TI  - [Rapidly progressive AL amyloidosis in a patient with relapsed multiple myeloma
      after achieving a complete response to tandem autologous PBSCT].
AB  - A 56-year-old male presented with pathological rib fracture and lumbago in 2006.
      He was diagnosed with multiple myeloma (IgG-lambda type, D&S stage IIIA, ISS 2).
      He was treated with VAD therapy and tandem auto-PBSCT, and achieved CR in 2007.
      He was followed without chemotherapy, but relapsed in 2009. He received
      lenalidomide plus dexamethasone and bortezomib plus dexamethasone and achieved PR
      which was sustained for 25 months. In 2012, he developed edema of the lower legs
      and pleural effusion, and was diagnosed as having nephrotic syndrome and heart
      failure due to AL amyloidosis. He died of renal failure and heart failure 3
      months after this diagnosis. Autopsy findings showed amyloid deposition in many
      organs including the heart, kidneys, liver, spleen, and intestines. Development
      of rapidly progressive AL amyloidosis is a rare complication of relapse after the
      achievement of CR, but careful monitoring is needed in patients with multiple
      myeloma. 

PMID- 24452149
TI  - [Successful treatment with azacitidine for a patient with relapsed
      myelodysplastic syndrome after cord blood transplantation].
AB  - A 72-year-old man visited our hospital in July 2009 with a major complaint of
      lightheadedness. Based on bone marrow aspiration, myelodysplastic syndrome (MDS),
      refractory anemia with excessive blast-2 was diagnosed. Complete remission (CR)
      was achieved after low-dose cytarabine and aclarubicin therapy. After two courses
      of low-dose cytarabine therapy, at the first CR, cord blood transplantation (CBT)
      was performed after reduced-intensity conditioning in January 2010. However,
      recurrence was found in September 2011. Azacitidine (AZA) was administered
      subcutaneously daily for either 7 or 5 days and repeated every 4 weeks at doses
      of 100 mg/day. During nine cycles of AZA treatment, no graft-versus-host disease
      was observed and no transfusions of red cells/platelet concentrate were required.
      As of 1 year after the relapse was detected, the patient remains alive with
      stable disease. As there are few reports on AZA treatment for patients with MDS
      who experience relapse after CBT, the efficacy of this approach remains unclear.
      Further clinical trials including dose, duration, and number of cycles of AZA for
      MDS patients who relapse after transplantation are required. 

PMID- 24452150
TI  - [Latent malignant lymphoma diagnosed at autopsy in a patient with cold agglutinin
      disease coexisting thrombotic thrombocytopenic purpura].
AB  - An 89-year-old woman presented to our hospital with hemolytic anemia and a high
      titer of cold agglutinins. Red cell agglutination was observed on a blood smear.
      Agglutination visibly decreased after warming the blood; therefore, the patient
      was diagnosed with cold agglutinin disease (CAD). Bone marrow aspiration revealed
      no infiltration of malignant cells. Computed tomography indicated moderate
      splenomegaly. The patient had neither an infection nor autoimmune disease.
      Initial steroid therapy was ineffective and hemolysis worsened. Meanwhile,
      thrombocytopenia, delirium, fever, and schistocytes in the blood were observed.
      The progression of hemolysis was attributed not only to CAD but also to
      coexisting thrombotic thrombocytopenic purpura (TTP) because of the decreased
      ADAMTS 13 level. Autopsy revealed mild paraaortic lymphadenopathy and
      splenomegaly. Microscopic examination revealed lymphoma cell infiltration in the
      spleen, liver, bone marrow, and paraaortic lymph nodes. These observations
      suggested that TTP and CAD were both secondary complications. This case
      highlights the importance of an autopsy for the detection of latent lymphoma,
      which can be difficult to diagnose before the patient's death. Careful
      examination to exclude lymphomas is important in patients with CAD at the time of
      diagnosis. 

PMID- 24452151
TI  - [Sodium-losing nephropathy caused by tacrolimus after allogeneic hematopoietic
      stem cell transplantation].
AB  - A 39-year-old woman (Case 1) and a 57-year-old woman (Case 2) underwent
      allogeneic bone marrow transplantation for acute lymphoblastic leukemia and
      follicular lymphoma, respectively. Both patients had received tacrolimus orally
      for treatment of or prophylaxis against graft-versus-host disease. Seventeen
      months (Case 1) and 2 months (Case 2) post-transplantation, when the trough level
      of tacrolimus was maintained around 10 ng/ml, the serum sodium levels of Cases 1
      and 2 decreased to 123.5 mEq/l and 125.6 mEq/l, respectively. Urinary sodium
      excretions increased to 186.8 mEq/day and 375.7 mEq/day, respectively. Sodium
      losing nephropathy due to tacrolimus was diagnosed, and reducing the dose of
      tacrolimus with no other intervention resulted in resolution of the hyponatremia.
      Although sporadic kidney transplantation cases with sodium-losing nephropathy due
      to tacrolimus have been reported, no prior cases with this complication after
      hematopoietic stem cell transplantation (HSCT) have been reported. Sodium-losing
      nephropathy should be recognized as one of the renal toxicities of tacrolimus in
      HSCT as well as kidney recipients. 

PMID- 24452152
TI  - [Primary myelofibrosis complicated by acquired hemophilia A and subsequent
      development of acute myeloid leukemia].
AB  - A 77-year-old man diagnosed with primary myelofibrosis (PMF), successfully
      controlled by thalidomide and prednisolone, was referred to us for massive
      subcutaneous bleeding involving the face, body, and all four limbs. Hemostatic
      studies showed prolonged activated partial thromboplastin time, decreased factor
      VIII coagulation, and a high factor VIII inhibitor titer, resulting in a
      diagnosis of acquired hemophilia A (AHA) for which he was treated with
      prednisolone and cyclophosphamide on admission. He developed right femoral
      intramuscular hemorrhage soon after immunosuppressive therapy and was treated
      with rituximab combined with activated prothrombin complex concentrates.
      Furthermore, he suffered complications of respiratory failure with increasing
      throat hemorrhaging. Recombinant activated factor VII (rFVIIa) was administered
      combined with methylprednisolone pulse therapy. Bleeding, including respiratory
      failure, was ameliorated with rFVIIa. Immunosuppressive rituximab therapy
      resolved AHA with marked efficacy. He died of Pneumocystis jiroveci pneumonitis.
      Autopsy showed transformation from PMF to acute myeloid leukemia. 

PMID- 24452153
TI  - [Diffuse large B-cell lymphoma with intravascular involvement of neoplastic CD5
      positive cells].
AB  - A 77-year-old man was admitted because of fever. A small number of large CD20
      positive neoplastic cells were seen in the bone marrow specimen. Clinical
      symptoms improved with oral prednisolone. After 11 months, abdominal CT scan
      revealed a liver mass. The biopsy specimen from the liver mass showed diffuse
      infiltration of large CD20-positive neoplastic cells. The patient was diagnosed
      as having diffuse large B-cell lymphoma. It was of particular interest that only
      neoplastic B cells within small blood vessels in the liver mass were positive for
      CD5. The patient died of lymphoma three months after diagnosis. 

PMID- 24452154
TI  - [Inv(16)-type acute myeloid leukemia with repeated skin infiltration without bone
      marrow relapse before and after allogeneic hematopoietic stem cell
      transplantation].
AB  - We report a 40-year-old woman diagnosed as having acute myeloid leukemia with
      CBFB-MYH11. Before and after stem cell transplantation in the phase of molecular
      remission of the marrow, CBFB-MYH11-positive cells were detected by RT-PCR
      analysis in skin lesions. The former was pathologically diagnosed as leukemic
      infiltration, while the latter was considered to be graft-versus-host disease. We
      can speculate that a low level of leukemic stem cells not detectable by RT-PCR
      analysis remained in the bone marrow, at least prior to transplantation. This
      case may suggest interesting biological features of inv(16)-type acute myeloid
      leukemia. 

PMID- 24452158
TI  - Evaluation of four single-locus markers for Leishmania species discrimination by
      sequencing.
AB  - Several genetic markers have been described for discriminating Leishmania
      species. In most reported cases, one or a few polymorphisms are the basis of
      species identification, and the methods were validated on a limited number of
      strains from a particular geographical region. Therefore, most techniques may
      underestimate the global intraspecies variability and are applicable only in
      certain areas. In addition, interlaboratory standardization is mostly absent,
      complicating comparisons among different studies. Here, we compared species
      typing results from all sequence polymorphisms found in four popular markers that
      can be applied directly on clinical samples: the miniexon or spliced leader, the
      internal transcribed spacer of the ribosomal DNA array, the 7SL RNA gene, and the
      heat shock protein 70 gene. Clustering was evaluated among 74 Leishmania strains,
      selected to represent a wide geographic distribution and genetic variability of
      the medically relevant species of the genus. Results were compared with a
      multilocus sequence typing (MLST) approach using 7 single-copy household genes
      and with multilocus enzyme electrophoresis (MLEE), still considered the gold
      standard by some. We show that strain groupings are highly congruent across the
      four different single-locus markers, MLST, and MLEE. Overall, the heat shock
      protein 70 gene and the miniexon presented the best resolutions for separating
      medically relevant species. As gene sequence analysis is validated here on a
      global scale, it is advocated as the method of choice for use in genetic,
      clinical, and epidemiological studies and for managing patients with unknown
      origins of infection, especially in Western infectious disease clinics dealing
      with imported leishmaniasis. 

PMID- 24452159
TI  - Evaluation of the Bruker MALDI Biotyper for identification of Gram-positive rods:
      development of a diagnostic algorithm for the clinical laboratory.
AB  - Reported matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) identification rates of Gram-positive rods (GPR) are
      low compared to identification rates of Gram-positive cocci. In this study, three
      sample preparation methods were compared for MALDI-TOF MS identification of 190
      well-characterized GPR strains: direct transfer, direct transfer-formic acid
      preparation, and ethanol-formic acid extraction. Using the interpretation
      criteria recommended by the manufacturer, identification rates were significantly
      higher for direct transfer-formic acid preparation and ethanol-formic acid
      extraction than for direct transfer. Reducing the species cutoff from 2.0 to 1.7
      significantly increased species identification rates. In a subsequent prospective
      study, 215 clinical GPR isolates were analyzed by MALDI-TOF MS, and the results
      were compared to those for identification using conventional methods, with
      discrepancies being resolved by 16S rRNA and rpoB gene analysis. Using the direct
      transfer-formic acid preparation and a species cutoff of 1.7, congruencies on the
      genus and species levels of 87.4% and 79.1%, respectively, were achieved. In
      addition, the rate of nonidentified isolates dropped from 12.1% to 5.6% when
      using an extended database, i.e., the Bruker database amended by reference
      spectra of the 190 GPR of the retrospective study. Our data demonstrate three
      ways to improve GPR identification by the Bruker MALDI Biotyper, (i) optimize
      sample preparation using formic acid, (ii) reduce cutoff scores for species
      identification, and (iii) expand the database. Based on our results, we suggest
      an identification algorithm for the clinical laboratory combining MALDI-TOF MS
      with nucleic acid sequencing. 

PMID- 24452160
TI  - Real-time cellular analysis coupled with a specimen enrichment accurately detects
      and quantifies Clostridium difficile toxins in stool.
AB  - We describe here the use of an immunomagnetic separation enrichment process
      coupled with a modified real-time cellular analysis (RTCA) system (RTCA version
      2) for the detection of C. difficile toxin (CDT) in stool. The limit of CDT
      detection by RTCA version 2 was 0.12 ng/ml. Among the consecutively collected 401
      diarrheal stool specimens, 53 (13.2%) were toxin-producing C. difficile strains
      by quantitative toxigenic culture (qTC); bacterial loads ranged from 3.00 * 10(1)
      to 3.69 * 10(6) CFU/ml. The RTCA version 2 method detected CDT in 51 samples,
      resulting in a sensitivity of 96.2%, a specificity of 99.7%, and positive and
      negative predictive values of 98.1% and 99.4%, respectively. The positive step
      time ranged from 1.43 to 35.85 h, with <24 h for 80% of the samples. The CDT
      concentrations in stool samples determined by RTCA version 2 correlated with
      toxigenic C. difficile bacterial load (R(2) = 0.554, P = 0.00002) by qTC as well
      as the threshold cycle (R(2) = 0.343, P = 0.014) by real-time PCR. A
      statistically significant correlation between the CDT concentrations and the
      clinical severity of CDI was observed (P = 0.015). The sensitivity of the RTCA
      version 2 assay for the detection of functional toxins in stool specimens was
      significantly improved when the immunomagnetic separation enrichment process was
      incorporated. More than 80% positive results can be obtained within 24 h. The
      stool specimen CDT concentration derived using the RTCA version 2 assay
      correlates with clinical severity and may be used as a marker for monitoring the
      status of CDI. 

PMID- 24452161
TI  - Serodiagnosis using microagglutination assay during the food-poisoning outbreak
      in Japan caused by consumption of raw beef contaminated with enterohemorrhagic
      Escherichia coli O111 and O157.
AB  - A microagglutination (MA) assay to identify antibodies to Escherichia coli O111
      and O157 was conducted in sera collected from 60 patients during a food-poisoning
      outbreak affecting 181 patients in Japan which was caused by the consumption of
      contaminated raw beef. Enterohemorrhagic E. coli (EHEC) O111:H8 and/or O157:H7
      was isolated from the stools of some of the patients, but the total rate of
      positivity for antibodies to O111 (45/60, 75.0%) was significantly higher than
      that for antibodies to O157 (10/60, 16.7%). The MA titers of antibodies to O111
      measured in patients with hemolytic-uremic syndrome and bloody diarrhea were
      higher than those measured in patients with only diarrhea. In patients from whose
      stool no isolates of E. coli O111 and O157 were obtained, the positive antibody
      detection rates were 12/19 (63.2%) for O111 and 2/19 (10.5%) for O157, and the MA
      titers of antibodies to O111 measured were higher than those to O157. Similarly,
      the MA titers of antibodies to O111 were significantly higher than those to O157,
      regardless of the other groups, including groups O111, O111 and O157, and O157.
      These serodiagnosis results suggest that EHEC O111:H8 stx2 played a primary role
      in the pathogenesis of this outbreak. Furthermore, our findings suggest that the
      isolates from the patients' stool specimens were not always the major causative
      pathogen in patients with multiple EHEC infections, because the sera from
      patients from whose stools only O157 was isolated were positive for antibodies to
      O111. Measuring antibodies to E. coli O antigen is helpful especially in cases
      with multiple EHEC infections, even with a non-O157 serotype. 

PMID- 24452162
TI  - Simultaneous detection and discrimination of virulent and benign Dichelobacter
      nodosus in sheep of flocks affected by foot rot and in clinically healthy flocks
      by competitive real-time PCR.
AB  - Ovine foot rot caused by Dichelobacter nodosus is affecting sheep worldwide. The
      current diagnostic methods are difficult and cumbersome. Here, we present a
      competitive real-time PCR based on allelic discrimination of the protease genes
      aprV2 and aprB2. This method allows direct detection and differentiation of
      virulent and benign D. nodosus from interdigital skin swabs in a single test.
      Clinically affected sheep harbored high loads of only virulent strains, whereas
      healthy sheep had lower loads of predominantly benign strains. 

PMID- 24452163
TI  - Small colony variant of methicillin-resistant Staphylococcus pseudintermedius
      ST71 presenting as a sticky phenotype.
AB  - We first observed the phenomenon of small colony variants (SCVs) in a
      Staphylococcus pseudintermedius sequence type 71 (ST71) strain, isolated from a
      non-pet owner. Although we found that small-sized colonies share main features
      with Staphylococcus aureus SCVs, they nevertheless show a novel, particular, and
      sticky phenotype, whose expression was extremely stable, even after
      subcultivation. 

PMID- 24452164
TI  - Mycobacterium paraffinicum causing symptomatic pulmonary infection.
AB  - Mycobacterium paraffinicum has been newly recognized as a species. A case of
      symptomatic pulmonary infection caused by M. paraffinicum is described, and as
      far as we know, this is the first case of the organism as a human pathogen. 

PMID- 24452165
TI  - False-positive reaction of L-canavanine glycine bromothymol blue medium with
      Candida famata.

PMID- 24452166
TI  - Phenotypic and genotypic characterization of Canadian clinical isolates of Vibrio
      parahaemolyticus collected from 2000 to 2009.
AB  - Vibrio parahaemolyticus is the leading bacterial cause of food-borne illness due
      to the consumption of contaminated seafood. The aim of the present study was to
      determine the population of its subtypes and establish a better understanding of
      the various types of V. parahaemolyticus strains that are causing human illness
      in Canada. The subtypes for 100 human clinical isolates of V. parahaemolyticus
      collected between 2000 and 2009 were determined by performing serotyping,
      ribotyping, pulsed-field gel electrophoresis, and multilocus sequence typing.
      Within this panel of strains, there was a high level of diversity (between 22 and
      53 subtypes per method), but the presence of predominant clones with congruent
      subtypes between the various methods was also observed. For example, all 32
      isolates belonging to sequence type 36 (ST36) were from serogroup O4, while 31 of
      them were ribotype EcoVib235-287, and 24 of the 32 were SfiI pulsed-field gel
      electrophoresis (PFGE) pattern VPSF1.0001. With regard to the presence of known
      virulence genes, 74 of the 100 isolates were PCR positive for the presence of the
      thermostable direct hemolysin (tdh); and 59 of these 74 strains also contained
      the second virulence marker, the tdh-related hemolysin (trh). The detection of
      trh was more predominant (81%) among the clinical isolates, and only four (4%) of
      the clinical isolates tested negative for the presence of both tdh and trh. This
      database, comprising 100 clinical isolates of V. parahaemolyticus strains from
      Canada, forms a baseline understanding of subtype diversity for future source
      attribution and other epidemiologic studies.

PMID- 24452167
TI  - Twenty-five-year outbreak of Pseudomonas aeruginosa infecting individuals with
      cystic fibrosis: identification of the prairie epidemic strain.
AB  - Transmissible strains of Pseudomonas aeruginosa have been described for cystic
      fibrosis (CF) and may be associated with a worse prognosis. Using a comprehensive
      strain biobank spanning 3 decades, we sought to determine the prevalence and
      stability of chronic P. aeruginosa infection in an adult population. P.
      aeruginosa isolates from sputum samples collected at initial enrollment in our
      adult clinic and at the most recent clinic visit were examined by a combination
      of pulsed-field gel electrophoresis and multilocus sequence typing and compared
      against a collection of established transmissible and local non-CF bronchiectasis
      (nCFB) isolates. A total of 372 isolates from 107 patients, spanning 674 patient
      years, including 66 patients with matched isolates from initial and final
      encounters, were screened. A novel clone with increased antibacterial resistance,
      termed the prairie epidemic strain (PES), was found in 29% (31/107 patients) of
      chronically infected patients referred from multiple prairie-based CF centers.
      This isolate was not found in those diagnosed with CF as adults or in a control
      population with nCFB. While 90% (60/66 patients) of patients had stable infection
      over a mean of 10.8 years, five patients experienced strain displacement of
      unique isolates, with PES occurring within 2 years of transitioning to adult
      care. PES has been present in our cohort since at least 1987, is unique to CF,
      generally establishes chronic infection during childhood, and has been found in
      patients at the time of transition of patients from multiple prairie-based CF
      clinics, suggesting broad endemicity. Studies are under way to evaluate the
      clinical implications of PES infection. 

PMID- 24452168
TI  - Concordance of PCR and culture from nasal swabs for detection of methicillin
      resistant Staphylococcus aureus in a setting of concurrent antistaphylococcal
      antibiotics.
AB  - The effect of concurrent administration of antibiotics on the detection of
      methicillin-resistant Staphylococcus aureus (MRSA) remains unresolved. Here, we
      assessed the concordance of paired nasal swabs processed using commercial PCR and
      culture and found high concordance in both the absence and presence of
      antibiotics with activity against MRSA (93.7% [95% confidence interval [CI],
      88.1%, 96.8%] and 90.9% [95% CI, 84.8%, 94.7%], respectively), although PCR was
      more likely to be positive in the presence of antibiotics. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT01234831.). 

PMID- 24452169
TI  - Performance of phenotypic tests for detection of penicillinase in Staphylococcus
      aureus isolates from Australia.
AB  - Recent studies have shown that chromogenic cephalosporin tests are inferior to
      disc zone edge tests in detecting penicillinase in Staphylococcus aureus
      isolates, resulting in a change to CLSI and EUCAST guidelines in 2012. We sought
      to confirm these findings using Australian isolates and compare the performance
      of the CLSI and EUCAST methods, which use different disc strengths, penicillin at
      10 units (P10) and 1 unit (P1), respectively. Using blaZ PCR as the reference
      standard, the sensitivities of the tests for detection of penicillinase
      production were as follows: Cefinase disc test, 24/38 isolates (63%); P10 disc
      zone edge test, 34/38 isolates (89%); P10 disc diameter test, 25/38 isolates
      (66%); P1 disc zone edge test, 38/38 isolates (100%); and P1 disc diameter test,
      38/38 isolates (100%). We also found that the P10 disc zone edge test reading was
      interpreted differently by the clinical laboratory and the study investigators in
      11% of instances. Our findings support those of previous studies showing that
      chromogenic cephalosporin-based beta-lactamase tests are inferior to disc methods
      in detecting S. aureus penicillinase. We also conclude that the EUCAST method
      using the P1 disc has the best performance, particularly because the P1 disc zone
      diameter reading closely correlated with penicillinase production and reading of
      the disc zone diameter is less subjective than reading of the zone edge. 

PMID- 24452170
TI  - Empyema caused by Prevotella bivia complicating an unusual case of spontaneous
      chylothorax.
AB  - Spontaneous chylothorax is rare in adults. We present an unusual case that was
      complicated by Prevotella bivia empyema. Full recovery was achieved with chest
      tube drainage and prompt treatment with intravenous clindamycin. 

PMID- 24452171
TI  - PCR-based in vitro synthesis of hepatitis C virus NS3 protease for rapid
      phenotypic resistance testing of protease inhibitors.
AB  - Protease inhibitors (PIs) targeting the hepatitis C virus (HCV) NS3 protease,
      such as telaprevir, have significantly improved the sustained virologic response
      (SVR) rates of HCV genotype 1 antiviral therapy. Given the expanding antiviral
      therapy regimen, fast HCV PI resistance assays are urgently needed. In this view,
      we have developed a novel phenotypic resistance test for HCV PIs based on in
      vitro synthesis of patient-derived HCV NS3 protease and subsequent enzymatic
      testing in a fluorescent readout. The enzymatically active HCV NS3 proteases were
      synthesized from PCR-derived templates by an Escherichia coli S30 extract system.
      Tests of the protease genes with known mutations for telaprevir resistance showed
      that the phenotypic resistance test was fast, with a total turnaround time of <10
      h, and was fully in agreement with the previous resistance results. The initial
      tests with 38 treatment-naive serum samples showed that the method was
      significantly less laborious and faster than currently available phenotypic
      resistance assays of HCV NS3 PIs. 

PMID- 24452173
TI  - Comparative assessment of automated nucleic acid sample extraction equipment for
      biothreat agents.
AB  - Magnetic beads offer superior impurity removal and nucleic acid selection over
      older extraction methods. The performances of nucleic acid extraction of
      biothreat agents in blood or buffer by easyMAG, MagNA Pure, EZ1 Advanced XL, and
      Nordiag Arrow were evaluated. All instruments showed excellent performance in
      blood; however, the easyMAG had the best precision and versatility. 

PMID- 24452178
TI  - Solution-phase catalytic synthesis, characterization and growth kinetics of Ag2S
      CdS matchstick-like heteronanostructures.
AB  - A facile catalytic growth route was developed for the low-temperature solution
      synthesis of Ag2S-CdS matchstick-like heteronanostructures in oleylamine, which
      are composed of a Ag2S spherical head and a CdS rod-like stem. Ag2S nanoseeds
      acted as an effective catalyst for the growth of CdS nanorods and remained at the
      tip of the resultant nanorods, leading to the formation of Ag2S-CdS
      heterostructures with a matchstick shape. The diameter of the Ag2S heads and the
      length of the CdS stems could be easily controlled by varying the molar ratios of
      the Ag/Cd precursors. The differential scanning calorimetry (DSC) and variable
      temperature X-ray diffraction (XRD) studies confirmed that Ag2S catalytic seeds
      underwent a phase change, that is, they were in a high-temperature superionic
      conducting cubic structure during the CdS nanorod growth and then converted to a
      low-temperature monoclinic crystal structure as the reaction was cooled to room
      temperature. The influence of synthetic temperature on the product morphology was
      investigated and the morphological evolution at different growth stages was
      monitored using transmission electron microscopy (TEM). Furthermore, the growth
      kinetics of the Ag2S-CdS matchstick-like heteronanostructures, including the
      dissolution, nucleation and growth of CdS within the Ag2S catalyst, was
      reasonably discussed on the basis of the structural characteristics of the
      superionic cubic Ag2S catalyst and the low solubility of CdS in Ag2S derived from
      the Ag2S-CdS binary phase diagram. 

PMID- 24452175
TI  - Detection of Campylobacter in stool and determination of significance by culture,
      enzyme immunoassay, and PCR in developing countries.
AB  - Campylobacter is a common bacterial enteropathogen that can be detected in stool
      by culture, enzyme immunoassay (EIA), or PCR. We compared culture for C.
      jejuni/C. coli, EIA (ProSpecT), and duplex PCR to distinguish Campylobacter
      jejuni/C. coli and non-jejuni/coli Campylobacter on 432 diarrheal and matched
      control stool samples from infants in a multisite longitudinal study of enteric
      infections in Tanzania, Bangladesh, and Peru. The sensitivity and specificity of
      culture were 8.5% and 97.6%, respectively, compared with the results of EIA and
      8.7% and 98.0%, respectively, compared with the results of PCR for C. jejuni/C.
      coli. Most (71.6%) EIA-positive samples were positive by PCR for C. jejuni/C.
      coli, but 27.6% were positive for non-jejuni/coli Campylobacter species.
      Sequencing of 16S rRNA from 53 of these non-jejuni/coli Campylobacter samples
      showed that it most closely matched the 16S rRNA of C. hyointestinalis subsp.
      lawsonii (56%), C. troglodytis (33%), C. upsaliensis (7.7%), and C. jejuni/C.
      coli (2.6%). Campylobacter-negative stool spiked with each of the above-mentioned
      Campylobacter species revealed reactivity with EIA. PCR detection of
      Campylobacter species was strongly associated with diarrhea in Peru (odds ratio
      [OR] = 3.66, P < 0.001) but not in Tanzania (OR = 1.56, P = 0.24) or Bangladesh
      (OR = 1.13, P = 0.75). According to PCR, Campylobacter jejuni/C. coli infections
      represented less than half of all infections with Campylobacter species. In sum,
      in infants in developing country settings, the ProSpecT EIA and PCR for
      Campylobacter reveal extremely high rates of positivity. We propose the use of
      PCR because it retains high sensitivity, can ascertain burden, and can
      distinguish between Campylobacter infections at the species level. 

PMID- 24452174
TI  - Misidentification of Aspergillus nomius and Aspergillus tamarii as Aspergillus
      flavus: characterization by internal transcribed spacer, beta-Tubulin, and
      calmodulin gene sequencing, metabolic fingerprinting, and matrix-assisted laser
      desorption ionization-time of flight mass spectrometry.
AB  - Aspergillus nomius and Aspergillus tamarii are Aspergillus species that
      phenotypically resemble Aspergillus flavus. In the last decade, a number of case
      reports have identified A. nomius and A. tamarii as causes of human infections.
      In this study, using an internal transcribed spacer, beta-tubulin, and calmodulin
      gene sequencing, only 8 of 11 clinical isolates reported as A. flavus in our
      clinical microbiology laboratory by phenotypic methods were identified as A.
      flavus. The other three isolates were A. nomius (n = 2) or A. tamarii (n = 1).
      The results corresponded with those of metabolic fingerprinting, in which the A.
      flavus, A. nomius, and A. tamarii strains were separated into three clusters
      based on ultra-high-performance liquid chromatography-tandem mass spectrometry
      (UHPLC MS) analysis. The first two patients with A. nomius infections had
      invasive aspergillosis and chronic cavitary and fibrosing pulmonary and pleural
      aspergillosis, respectively, whereas the third patient had A. tamarii
      colonization of the airway. Identification of the 11 clinical isolates and three
      reference strains by matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS) showed that only six of the nine strains of A.
      flavus were identified correctly. None of the strains of A. nomius and A. tamarii
      was correctly identified. beta-Tubulin or the calmodulin gene should be the gene
      target of choice for identifying A. flavus, A. nomius, and A. tamarii. To improve
      the usefulness of MALDI-TOF MS, the number of strains for each species in MALDI
      TOF MS databases should be expanded to cover intraspecies variability. 

PMID- 24452176
TI  - A molecular surveillance reveals the prevalence of Vibrio cholerae O139 isolates
      in China from 1993 to 2012.
AB  - Vibrio cholerae serogroup O139 was first identified in 1992 in India and
      Bangladesh, in association with major epidemics of cholera in both countries;
      cases were noted shortly thereafter in China. We characterized 211 V. cholerae
      O139 isolates that were isolated at multiple sites in China between 1993 and 2012
      from patients (n = 92) and the environment (n = 119). Among clinical isolates, 88
      (95.7%) of 92 were toxigenic, compared with 47 (39.5%) of 119 environmental
      isolates. Toxigenic isolates carried the El Tor CTX prophage and toxin
      coregulated pilus A gene (tcpA), as well as the Vibrio seventh pandemic island I
      (VSP-I) and VSP-II. Among a subset of 42 toxigenic isolates screened by
      multilocus sequence typing (MLST), all were in the same sequence type as a
      clinical isolate (MO45) from the original Indian outbreak. Nontoxigenic isolates,
      in contrast, generally lacked VSP-I and -II, and fell within 13 additional
      sequence types in two clonal complexes distinct from the toxigenic isolates. In
      further pulsed-field gel electrophoresis (PFGE) (with NotI digestion) studies,
      toxigenic isolates formed 60 pulsotypes clustered in one group, while the
      nontoxigenic isolates formed 43 pulsotypes which clustered into 3 different
      groups. Our data suggest that toxigenic O139 isolates from widely divergent
      geographic locations, while showing some diversity, have maintained a relatively
      tight clonal structure across a 20-year time span. Nontoxigenic isolates, in
      contrast, exhibited greater diversity, with multiple clonal lineages, than did
      their toxigenic counterparts.

PMID- 24452180
TI  - The roles of density-tunable surface oxygen vacancy over bouquet-like Bi2O3 in
      enhancing photocatalytic activity.
AB  - Bouquet-like hierarchical Bi2O3 photocatalyst materials with high-density surface
      oxygen vacancy are synthesized via a hydrothermal method by the synergetic
      control of NaOH and a polyvinyl alcohol (PVA) stabilizer. The OH(-) ion addition
      led to the formation of more relaxed PVA macromolecular clusters, as a result, a
      thinner PVA film was formed, the species adsorbed on the surface of the produced
      Bi2O3 crystal nucleus could tune both the surface microstructure size and oxygen
      vacancy density via controlling the velocity, transfer and reaction of the OH(-)
      ions. The significant enhancement of photocatalytic performances could be
      attributed to the high density of the surface oxygen vacancy which was propitious
      to the charge separation efficiencies, distribution characteristic, and its role
      in a photo-redox reaction. A turnable-bending self-assembly mechanism was
      proposed to clarify the formation process of the bouquet-like hierarchical
      structure. 

PMID- 24452179
TI  - Antitumor activity of CDA-II, a urinary preparation, on human multiple myeloma
      cell lines via the mitochondrial pathway.
AB  - Cell differentiation agent II (CDA-II) is a DNA methyltransferase inhibitor
      isolated from healthy human urine. In the present study, the antitumor activity
      of CDA-II on human multiple myeloma (MM) cell lines via the mitochondrial pathway
      was first revealed. The human MM cell lines were exposed to CDA-II. Cytotoxicity,
      caspase activation, apoptosis and the effects on the mitochondrial pathway were
      assessed. CDA-II was capable of decreasing the depolarized mitochondrial
      membranes and activating caspase-3 and -9 and poly (ADP-ribose) polymerase in MM
      cells treated with CDA-II. CDA-II induced caspase-dependent cell death
      accompanied by a significant decrease in X-linked inhibitor of apoptosis protein
      (XIAP), survivin and Mcl-1 levels. The caspase-3 inhibitor, Z-DEVD-FMK, inhibited
      CDA-II-induced apoptosis. CDA-II potently increased the Bax levels, decreased the
      Bcl-2/Bax ratio and decreased the expression of the downstream targets of NF
      kappaB. In conclusion, the results of the present study demonstrated that CDA-II
      treatment leads to the inhibition of p65 nuclear localization and potently
      induces caspase-dependent apoptosis in MM cells mediated through the
      mitochondrial pathway at low nanomolar concentrations. These results indicate
      that CDA-II is a novel inhibitor of NF-kappaB activity, with notable antimyeloma
      efficacy. This study provides a rationale for the clinical investigation of CDA
      II in human MM.

PMID- 24452181
TI  - Semi-basements used as dwellings: hygienic considerations and analysis of the
      regulations.
AB  - Current housing shortage in Italy is forcing a growing number of individuals to
      use as living environment spaces that were originally devoted to other purposes.
      Among such spaces, semi-basements hold a particular relevance because of their
      specific characteristics and their effects on human health. The authors analyse
      the relatively scarce legislation about this topic at both national and regional
      level. The local Building Codes of the ten most populous cities of Italy are
      reviewed, assessing whether the use of semi-basements as living spaces is allowed
      and, if so, which restrictions and requirements are imposed. The authors conclude
      that, on one hand, further research is strongly needed to estimate the amount of
      exposed population and their health risk, on the other the existing legislation
      on the topic is often discretionary and deeply unhomogeneous across the country. 

PMID- 24452182
TI  - [Molecular epidemiology of infectious diseases: analytical methods and results
      interpretation].
AB  - Molecular typing and fingerprinting of microbial pathogens represent an essential
      tool for the epidemiological surveillance, outbreak detection and control of
      infectious diseases. Indeed, epidemiological investigation without genotyping
      data may not provide comprehensive information to allow the most appropriate
      interventions; despite this consideration, some barriers still hamper the routine
      application and interpretation of molecular typing data. In this paper, the most
      important methods currently used for characterization of pathogenic
      microorganisms for microbial source tracking and for the identification of clonal
      relationships among different isolates, are described according to their
      principles, advantages and limitations. Criteria for their evaluation and
      guidelines for the correct interpretation of results are also proposed. Molecular
      typing methods can be grouped into four categories based on different
      methodological principles, which include the characterization of restriction
      sites in genomic or plasmid DNA; the amplification of specific genetic targets;
      the restriction enzyme digestion and the subsequent amplification; sequence
      analysis. Although the development and the extensive use of molecular typing
      systems have greatly improved the understanding of the infectious diseases
      epidemiology, the rapid diversification, partial evaluation and lack of
      comparative data on the methods have raised significant questions about the
      selection of the most appropriate typing method, as well as difficulties for the
      lack of consensus about the interpretation of the results and nomenclature used
      for interpretation. Several criteria should be considered in order to evaluate
      the intrinsic performance and practical advantages of a typing system. However
      none of the available genotyping methods fully meets all these requirements.
      Therefore, the combined use of different approaches may lead to a more precise
      characterization and discrimination of isolates than a single method, especially
      if used in a hierarchical manner. The interpretation of the molecular results
      differs according to the typing system's characteristics: for example in the
      restriction fragments-based analysis, the divergences or the similarity
      percentages among the profiles are evaluated, whilst the differences in terms of
      number and intensity of bands are analyzed in the amplification-based approaches.
      Moreover, a correct interpretation of molecular results significantly depends by
      other critical factors, such as the comprehension of the typing system and data
      quality, the microbial diversity, and the epidemiological context in which the
      method is used. The analysis of PFGE data, considered as the "gold standard", is
      based on the differences of the number and position of bands patterns, although
      recent recommendations are now available from the Centers for Diseases Control
      and Prevention (CDC) for a more accurate interpretation, which also include the
      evaluation of the gel quality, the genetic diversity of the microorganism, the
      time and geographical scale of an epidemic event. Future advances in the
      molecular typing technologies indeed will provide rapid methodological
      improvements, such as a greater degree of automation, better resolution, higher
      throughput, and a greater availability of dedicated bioinformatics tools. These
      factors will all contribute to an increasing application of genotyping methods to
      better understand the epidemiology of infectious diseases, and to implement,
      along with the strengthened international and interdisciplinary partnerships,
      more effective control and prevention strategies for Public Health improvements. 

PMID- 24452172
TI  - Genomic portrait of the evolution and epidemic spread of a recently emerged
      multidrug-resistant Shigella flexneri clone in China.
AB  - Shigella flexneri is the major cause of shigellosis in developing countries. A
      new S. flexneri serotype, Xv, appeared in 2000 and replaced serotype 2a as the
      most prevalent serotype in China. Serotype Xv is a variant of serotype X, with
      phosphoethanolamine modification of its O antigen mediated by a plasmid that
      contained the opt gene. Serotype Xv isolates belong to sequence type 91 (ST91).
      In this study, whole-genome sequencing of 59 S. flexneri isolates of 14 serotypes
      (serotypes 1 to 4, Y, Yv, X, and Xv) indicated that ST91 arose around 1993 by
      acquiring multidrug resistance (MDR) and spread across China within a decade. A
      comparative analysis of the chromosome and opt-carrying plasmid pSFXv_2 revealed
      independent origins of 3 serotype Xv clusters in China, with different divergence
      times. Using 18 cluster-dividing single-nucleotide polymorphisms (SNPs), SNP
      typing divided 380 isolates from 3 provinces (Henan, Gansu, and Anhui) into 5 SNP
      genotypes (SGs). One SG predominated in each province, but substantial
      interregional spread of SGs was also evident. These findings suggest that MDR is
      the key selective pressure for the emergence of the S. flexneri epidemic clone
      and that Shigella epidemics in China were caused by a combination of local
      expansion and interregional spread of serotype Xv. 

PMID- 24452183
TI  - Quality of life, psychological wellbeing and resilience: a survey on the Italian
      population living in a new lodging after the earthquake of April 2009.
AB  - OBJECTIVE: The aim of this study is to estimate the quality of life and the
      psychological wellbeing as a result of the earthquake which occurred the 6th of
      April 2009 and that struck the population of the city of L'Aquila. METHODS: A
      random sample of 281 subjects, from the population that had the possibility of
      living in a temporary lodging provided by the State, were interviewed after the
      earthquake, during the period between July and October 2010. Two self
      administered questionnaires were used: the Psychological General Well-Being Index
      (PGWBI) and the Dispositional Resilience Scale (DRS II). RESULTS: The women's
      health status is worse than the men's, this is true both on a general level
      (79,24 vs 70,55), and on different estimated dimensions. Health status is
      significantly worse in older age groups (F2;245=4,34, p=0,0140): the elderly
      appear to be more depressed (F2;245=6,52, p=0,0017) and to have less self-control
      (F2;245=3,06, p=0,0487) than the younger. CONCLUSIONS: Generally women tend to
      experience greater emotional involvement in social and interpersonal
      relationships. Although many months have passed since the catastrophic event,
      feelings of disease and a sense of impotence (about life) are still persistent in
      people, even though they generally are hopeful about the future.

PMID- 24452184
TI  - [Public health strategies in the prevention of induced abortion. An experience of
      interprofessional education based strategy].
AB  - In Italy recent statistics show a huge difference between abortion rate among
      Italian and migrant women: is it an inequity in health? The Italian Ministry of
      Health / Center for Disease Prevention and Control, which recognized this issue
      as a specific public health problem, has financed a national Project whose aim
      was the prevention of abortion among migrant women. The Project was characterized
      by a multitasking approach: 1) information and health education of migrant women
      and their communities; 2) education of health and social care professionals; 3)
      analysis and development of new proposals for the networks of services directed
      towards the improvement of woman's health. In this article the Authors describe
      the main characteristics of the realized intervention of inter-professional
      education. It began with a multidisciplinary process for the identification of
      educational needs which has allowed the identification of educational goals. A
      Training of Trainers event was then organized in order to involve and make the
      ten Italian Regions partners of the Project aware of their responsibilities. A
      DVD collecting all the material of the course and other useful resources was
      produced in order to support the educational process. At the moment it is not
      possible to evaluate the medium- and long-time results of the process (e.g. the
      efficacy of educational interventions or the health outcomes related to the
      reduction of abortion among migrant women). Nevertheless all the actors involved
      have made positive evaluations on the usefulness of the process. 

PMID- 24452185
TI  - Effectiveness of two interventions in preventing traffic accidents: a systematic
      review.
AB  - BACKGROUND: The prevention of road traffic accidents should be considered a
      serious public health concern, since they are the eighth leading cause of death
      globally and the main cause of death for young people aged 15-29. Evidences from
      many countries show that successes in preventing road traffic injuries can be
      achieved through concerted efforts at national level. The aim of our study was to
      assess the effectiveness of two interventions to prevent road traffic accidents:
      the introduction of graduated driver licensing (GDL) and the interventions to
      improve pedestrian and cyclist visibility. METHODS: Our search started with a
      scoping review on the interventions to prevent road traffic accidents to allow
      the development of a logical framework of traffic accidents. Specific and
      answerable questions formulated according to PICO scheme and combinations of
      keywords were used to perform a systematic search in the following databases:
      Pubmed, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews
      of Effects (DARE), Health Evidence, Transport Research International
      Documentation (TRID) and Google. References of selected papers were searched.
      Only systematic reviews and meta-analyses were eligible. No temporal limits or
      linguistic filters were applied. RESULTS: 160 systematic reviews and meta
      analyses were found for the question of the introduction of GDL program and 188
      on the improvement of visibility in cyclists and pedestrians. After selection,
      four papers were included in qualitative synthesis for each question. All
      included studies underwent quality evaluation. GDL programs seem to be effective
      in reducing crash rates among young drivers, in particular in 16 year-old.
      Programs with more restrictions seem also to reduce fatal events. To improve
      visibility of pedestrians and cyclists, street lighting has been suggested as an
      intervention able to improve driver's visual capabilities and ability to detect
      roadway hazards and to prevent car crashes. Visibility aids (fluorescent
      materials, lamps, flashing lights and retroreflective materials) have the
      potential to increase visibility and enable drivers to detect pedestrians and
      cyclists earlier. CONCLUSIONS: The two interventions seem to be effective, but
      further examinations are needed to measure long-term effects. It is necessary to
      provide feasible studies in local context to estimate the impact of introduction
      of GDL programs or of some of their components and to improve interventions to
      increase visibility of pedestrians and cyclists.

PMID- 24452186
TI  - Food supplements: survey of the ASL TO3.
AB  - INTRODUCTION: In recent years, the increase of the consumption of supplements
      reveals problems concerning the safety of use. Current legislation states that
      supplements must be free of any therapeutic purpose and must have quality
      guarantees for the users' safety. The operators of the of Hygiene, Food and
      Nutrition Service (SIAN) of ASL TO 3 (province of Turin) conducted a surveillance
      in order to asses the situation on the territory, to know the use and consumption
      in local gyms. During the official control at the manufacturers / packers of
      supplements, located on the territory of the ASL TO 3, labels of supplement
      produced / packed were acquired, to analyze the components indicated, to carry
      out a deep evaluation of the individual product . METHODS: Updating of the
      register of companies located in the territory of the ASL TO 3 was carried out;
      and during the period October 2011-March 2013 the labels of the products of these
      companies have been found and analyzed. The detailed content of the labels
      (ingredients, dose, method of recruitment, composition, etc. ..) was written in a
      database. It was also checked how many local gyms marketed supplements, and, in a
      small sample, a questionnaire was administered to visitors, in order to assess
      consumption. RESULTS: 355 labels were acquired and loaded on the database. 80% of
      them falls within the category of supplements based on ingredients derived from
      plants or similar. For these products was evaluated the presence on the label of
      not allowed plant extracts (according to the Ministerial Decree of 9 July 2012):
      only 2 products (of the same company) contained an ingredient not allowed. In all
      the examined labels was evaluated the presence of the substances for which there
      are specific warnings: 97% of the label is compliant and 3% are not in
      compliance. In the analyzed products the indications for use mainly found on the
      labels are related to increased demand and/or reduced intake, followed by
      antioxidant action. The study also evaluated the sale of supplements at gyms
      located on the territory of ASLTO3: 59 gyms are available on territory, but only
      in one of them supplements are sold. Some customers of these gyms have filled a
      questionnaire concerning the consumption of supplements. The processing of the
      questionnaires showed that 27% of respondents in the past 2 years used only
      occasionally food supplements. For 42% of the subjects the use of these products
      was to achieve weight loss, for 33% for athletes and 17% have used specific
      products in the case of particular physiological situations such as pregnancy and
      lactation. The reasons that lead to the use of dietary supplements, in all cases,
      are attributed to the improvement of health status. In addition, in 50% of cases
      the pharmacist has led to the use of these products or, alternatively, friends
      and relatives. The general practitioner is often not informed even in case of
      disturbances introduced after their use (seen in 8% of our sample). The majority
      of the sample (58%) said that they had benefited from the use of supplements and
      they are aware (68%) that there could be contraindications. CONCLUSIONS: A
      greater knowledge of the topic, with attention focused on the entire supply chain
      of the product, is essential to ensure the safety of consumers in the use of food
      supplements. For these reasons a more detailed check on the procedure is
      essential: selection and verification of suppliers (especially for raw materials
      coming from Eastern countries, because they are not subjected to a thorough
      inspection); traceability of products marketed; correspondence between
      manufactured and authorized products. Finally, promote an awareness campaign at
      all levels is necessary, including general practitioners for a conscious
      purchase.

PMID- 24452187
TI  - Legionella contamination in hospitals of the Campania Region: five years of
      environmental surveillance results.
AB  - OBJECTIVE: The purpose of this study was to assess the presence and the
      distribution of Legionella serotypes in 50 hospital facilities in the Campania
      Region (Italy) through the sampling of their waters. METHODS: From January 2008
      to December 2012, in compliance with the Italian Monitoring Guidelines for
      Legionellosis, 4.842 water samples were collected from the end points of hot
      water distribution networks, air conditioning systems, boilers and cooling
      towers. RESULTS: 1.426 (29.4%) of the 4.842 samples resulted positive for
      Legionella spp, with a bacterial average of 3.40 log10 cfu/L. The frequency of
      Legionella isolation in the specimens progressively decreased during the study
      (43.8% in 2008 vs 22.9% in 2012). Samples from cooling towers (32.7%), showers
      and taps (31.9%) revealed a more frequent presence of the microorganism, although
      considerable bacterial concentration variability was found in all examined
      points. A bacterial average of 3.33 + 0.88 log10 cfu/L was detected in cooling
      towers, whereas the lowest values (2.89 + 0.92 cfu/L) were found in ACSs. The
      most frequently isolated species were L. pneumophila 2-14, detected in 60.6% of
      positive samples. Within serotypes, types 6 (23.8%), 8 (21.9%) and 3 (21.4%)
      resulted as being the most representative. CONCLUSIONS: A significant
      contamination was found in examined centers. It is therefore advisable to
      systematically implement currently available surveillance and monitoring
      strategies through the scrupulous monitoring of systems as well as through the
      application of validated and effective procedures.

PMID- 24452188
TI  - H1N1 pandemic influenza: habits and behaviour of the nurses. A public health
      issue.
AB  - BACKGROUND: One of the main concerns related to pandemic H1N1 influenza 2009 is
      the overwhelming burden on medical structures. The aim of this work is to study
      the behaviour and attitudes of Nurses in relation to the spreading pandemic in
      order to develop public health strategies. METHODS: During the spread of
      Pandemic, in winter 2009, an anonymous questionnaire online of thirty-four
      questions was available for participants. Data obtained were analyzed using
      descriptive, univariate and multivariate statistics. RESULTS: A total of 2313
      nurses were interviewed. In univariate analysis 72.6% of 573 males (versus 63.9%
      of 1740 females) have been talk to a doctor (p<0.001). The female group appear
      less likely to get vaccinated (60.3% vs 51.1%, p<0.001). Multivariate analysis
      revealed that to be worried (OR=2.82 95% CI: 2.31-3.46), female (OR=0.62 95% CI:
      0.51-0.77), age group 30-49 (OR=0.72 95% CI: 0.58-0.90) were associated with the
      willingness of Get vaccinated. CONCLUSIONS: Prevention, as washing hands and
      vaccination, are crucial in pandemics events. Given the low rates of acceptance
      of pandemic vaccination among nurses, public health bodies should consider
      campaign education, in order to prevent nosocomial transmission, to protect
      patients and the continuity of the essential health-care infrastructure.

PMID- 24452189
TI  - [Comparison of cultural methods for the recovery of Pseudomonas aeruginosa: the
      UNI EN ISO 16266 reference method and the alternative method Pseudalert(r)].
AB  - BACKGROUND: For the water analysis, for Pseudomonas aeruginosa a presumptive
      positive result can be achieved in 40- 48 hours using the traditional membrane
      filtration technique followed by an additional 24-48 hour confirmation stage.
      Conversely, the Pseudalert Quanti-TrayTM method can give confirmed results after
      24-28 hours. In this case, actively growing strains of Pseudomonas aeruginosa
      show a confirmed positive result when a specific enzyme cleaving the substrate in
      the reagent produces a blue fluorescence under 365 nm ultraviolet light. A
      comparison of the performance of the Pseudalert respect to the standard method
      was conducted using statistical methods. METHODS: Drinking water was analyzed in
      parallel with the membrane filtration technique using Pseudomonas CN agar (UNI EN
      ISO 16266) and the Pseudalert. Confirmation test are requested by the standard
      method and although Pseudalert Quanti-TrayTM gives confirmed results, all the
      positive isolates were also confirmed. Data were analyzed by statistical methods.
      RESULTS: For drinking water, Pseudalert showed a very high sensitivity (98,8%)
      and a high percentage of specificity (96,8%). From a total of 889 positive
      isolates, a very high confirmation rates (99,3%) was calculated. Statistical
      analyses confirmed that the two methods were not statistically different.
      CONCLUSIONS: These results indicate that the Pseudalert produces confirmed
      results in a shorter time than the standard reference method allowing the
      detection of Pseudomonas aeruginosa with no further confirmation steps. It could
      be a valid alternative method for the water analysis.

PMID- 24452190
TI  - Immunity status against poliomyelitis in childbearing women in a province of
      northern Italy.

PMID- 24452191
TI  - Immunity status against poliomyelitis in childbearing women in a province of
      northern Italy -- reply.

PMID- 24452193
TI  - Artificial synapse network on inorganic proton conductor for neuromorphic
      systems.
AB  - The basic units in our brain are neurons, and each neuron has more than 1,000
      synapse connections. Synapse is the basic structure for information transfer in
      an ever-changing manner, and short-term plasticity allows synapses to perform
      critical computational functions in neural circuits. Therefore, the major
      challenge for the hardware implementation of neuromorphic computation is to
      develop artificial synapse network. Here in-plane lateral-coupled oxide-based
      artificial synapse network coupled by proton neurotransmitters are self-assembled
      on glass substrates at room-temperature. A strong lateral modulation is observed
      due to the proton-related electrical-double-layer effect. Short-term plasticity
      behaviours, including paired-pulse facilitation, dynamic filtering and
      spatiotemporally correlated signal processing are mimicked. Such laterally
      coupled oxide-based protonic/electronic hybrid artificial synapse network
      proposed here is interesting for building future neuromorphic systems. 

PMID- 24452192
TI  - BurrH: a new modular DNA binding protein for genome engineering.
AB  - The last few years have seen the increasing development of new DNA targeting
      molecular tools and strategies for precise genome editing. However, opportunities
      subsist to either improve or expand the current toolbox and further broaden the
      scope of possible biotechnological applications. Here we report the discovery and
      the characterization of BurrH, a new modular DNA binding protein from
      Burkholderia rhizoxinica that is composed of highly polymorphic DNA targeting
      modules. We also engineered this scaffold to create a new class of designer
      nucleases that can be used to efficiently induce in vivo targeted mutagenesis and
      targeted gene insertion at a desired locus. 

PMID- 24452194
TI  - Clinical implications of pathogenic calcium crystals.
AB  - PURPOSE OF REVIEW: The role of intraarticular calcifications has been challenged
      over the past years, with respect to cartilage destruction, especially in
      osteoarthritis. RECENT FINDINGS: Main themes reviewed in this article will
      discuss prevalence of articular cartilage calcifications, mechanisms of cartilage
      calcifications, and mostly the pathogenic role of both calcium pyrophosphate and
      basic calcium phosphate crystals. SUMMARY: A direct pathogenic role of both
      calcium crystals has been depicted, in cartilage as a crystal-induced stress, or
      via acute or chronic crystal-induced synovitis.

PMID- 24452195
TI  - Priming with proangiogenic growth factors and endothelial progenitor cells
      improves revascularization in linear diabetic wounds.
AB  - In the present study, we investigated whether proangiogenic growth factors and
      endothelial progenitor cells (EPCs) induce favourable effects on cutaneous
      incisional wound healing in diabetic mice. The proangiogenic effects of human
      EPCs were initially analyzed using a HUVEC in vitro angiogenesis assay and an in
      vivo Matrigel assay in nude mice (n=12). For the diabetic wound model, 48 Balb/c
      mice with streptozotocin (STZ)-induced diabetes were divided randomly into 4
      groups (12 mice in each group). Subsequently, 3, 5 and 7 days before a 15-mm full
      thickness incisional skin wound was set, group 1 was pre-treated subcutaneously
      with a mixture of vascular endothelial growth factor (VEGF)/basic fibroblast
      growth factor (bFGF)/platelet-derived growth factor (PDGF) (3.5 ug of each),
      group 2 with 3.5 ug PDGF and group 3 with an aliquot of two million EPCs, whereas
      the control animals (group 4) were pre-treated with 0.2 ml saline solution. The
      wounds were assessed daily and the repaired tissues were harvested 7 days after
      complete wound closure. The angiogenesis assay demonstrated significantly
      increased sprout densities, areas and lengths in the EPC-treated group (all
      p<0.01). In the Matrigel assay, significantly increased microvessel densities,
      areas and sizes (all p<0.001) were also detected in the EPC-treated group. In the
      STZ-induced model of diabetes, the animals pre-treated with a combination of
      proangiogenic factors and EPCs showed in general, a more rapid wound closure.
      Vessel densities were >2-fold higher in the mice treated with a combination of
      proangiogenic factors and EPCs (p<0.05) and tensile strengths were higher in the
      groups treated with proangiogenic growth factors compared to the controls
      (p<0.05). These results suggest a beneficial effect of pre-treatment with
      proangiogenic growth factors and EPCs in incisional wound healing.

PMID- 24452196
TI  - Microporous Co@CoO nanoparticles with superior microwave absorption properties.
AB  - Nanoporous metal materials with many potential applications have been synthesized
      by a chemical dealloying approach. The fabrication of nanoporous metal
      nanoparticles (NPs), however, is still challenging due to the difficulties in
      producing suitable nanoscale precursors. Herein, nanoporous Co NPs of 31 nm have
      been successfully prepared by dealloying Co-Al NPs, and surprisingly they possess
      micropores in a range from 0.7 to 1.7 nm and a large surface area of 50 m(2) g(
      1). The crystalline size of the microporous NPs is 2-5 nm. Through the
      passivation process, the microporous Co NPs covered with CoO (Co@CoO) are
      generated as a result of the surface oxidation of Co. They exhibit better
      microwave absorption properties than their nonporous counterpart. An enhanced
      reflection loss (RL) value of -90.2 dB is obtained for the microporous Co@CoO NPs
      with a thickness of merely 1.3 mm. The absorption bandwidth corresponding to the
      RL below -10 dB reaches 7.2 GHz. The microwave absorption mechanism is discussed
      in terms of micropore morphology, core@shell structure and nanostructure. This
      novel microporous material may open new routes for designing high performance
      microwave absorbers. 

PMID- 24452197
TI  - Silicon isotopes indicate enhanced carbon export efficiency in the North Atlantic
      during deglaciation.
AB  - Today's Sargasso Sea is nutrient starved, except for episodic upwelling events
      caused by wind-driven winter mixing and eddies. Enhanced diatom opal burial in
      Sargasso Sea sediments indicates that silicic acid, a limiting nutrient today,
      may have been more available in subsurface waters during Heinrich Stadials,
      millennial-scale climate perturbations of the last glacial and deglaciation. Here
      we use the geochemistry of opal-forming organisms from different water depths to
      demonstrate changes in silicic acid supply and utilization during the most recent
      Heinrich Stadial. We suggest that during the early phase (17.5-18 ka), wind
      driven upwelling replenished silicic acid to the subsurface, resulting in low Si
      utilization. By 17 ka, stratification reduced the surface silicic acid supply
      leading to increased Si utilization efficiency. This abrupt shift in Si cycling
      would have contributed to high regional carbon export efficiency during the
      recent Heinrich Stadial, despite being a period of increasing atmospheric CO2.

PMID- 24452199
TI  - Lithography-assisted alignment control for preparation of mesoporous silica films
      with uniaxially oriented mesochannels.
AB  - We report the lithography-assisted alignment control of one-dimensional (1D)
      mesochannels. The effectiveness on both nonionic and cationic surfactants is
      discussed, and a continuous film with fully uniaxially oriented mesochannels is
      also successfully prepared. 

PMID- 24452200
TI  - Response to "the life table method of half-cycle correction: getting it right".

PMID- 24452201
TI  - Phosphorothioate-modified CpG oligodeoxynucleotide (CpG ODN) induces apoptosis of
      human hepatocellular carcinoma cells independent of TLR9.
AB  - Toll-like receptors (TLRs) expressed on cancer cells are closely associated with
      tumor development. In this study, we investigated the biological functions of the
      TLR9 ligand, CpG oligodeoxynucleotide (CpG ODN), on TLR9 expressed in the
      cytoplasm of hepatocellular carcinoma (HCC) cells. In vitro, human HCC cell lines
      were transfected with phosphorothioate-modified oligodeoxynucleotides TLR9
      agonist OND M362 and its negative control ODN M362 ctrl, which inhibited the
      proliferation of HCC cells by inducing apoptosis without altering the cell cycle.
      Interestingly, ODN M362 and ODN M362 Ctrl displayed a similar proapoptotic effect
      on HCC, possibly related to phosphorothioate modification of the structure of CpG
      ODN. Although both of them resulted in the upregulation of the TLR9 receptor,
      their effect on HCC apoptosis was independent of TLR9. They also upregulated
      inflammatory cytokines, but did not activate the NF-kappaB signaling pathway.
      Finally, the activities of ODN M362 and ODN M362 Ctrl were demonstrated in nude
      mice inoculated with HCC cells. These findings suggest that the phosphorothioate
      modified TLR9 agonist ODN M362, and its control, elicit antitumor activity in HCC
      cells and may serve as a novel therapeutic target for HCC therapy. 

PMID- 24452202
TI  - Cryoimmunotherapy with local co-administration of ex vivo generated dendritic
      cells and CpG-ODN immune adjuvant, elicits a specific antitumor immunity.
AB  - Cryoablation is a low-invasive surgical procedure for management of malignant
      tumors. Tissue destruction is obtained by repeated deep freezing and thawing and
      results in coagulative necrosis and in apoptosis. This procedure induces the
      release of tumor-associated antigens and proinflammatory factors into the
      microenvironment. Local administration of immature dendritic cells (DCs)
      potentiates the immune response induced by cryoablation. To further augment the
      induction of long-lasting antitumor immunity, we investigated the clinical value
      of combining cryoimmunotherapy consisting of cryoablation and inoculation of
      immature DCs with administration of the immune adjuvant, CpG
      oligodeoxynucleotides. Injection of the murine Lewis lung carcinoma, D122-luc-5.5
      that expresses the luciferase gene, results in spontaneous metastases, which can
      be easily monitored in vivo. The local tumor was treated by the combined
      treatment. The clinical outcome was assessed by monitoring tumor growth,
      metastasis in distant organs, overall survival, and protection from tumor
      recurrence. The nature of the induced T cell responses was analyzed. Combined
      cryoimmunotherapy results in reduced tumor growth, low metastasis and
      significantly prolonged survival. Moreover, this treatment induces antitumor
      memory that protected mice from rechallenge. The underlying suggested mechanisms
      are the generation of tumor-specific type 1 T cell responses, subsequent
      induction of cytotoxic T lymphocytes, and generation of systemic memory. Our data
      highlight the combined cryoimmunotherapy as a novel antitumor vaccine with
      promising preclinical results. Adjustment of this technique into practice will
      provide the therapeutic benefits of both, ablation of the primary tumor and
      induction of robust antitumor and antimetastatic immunity. 

PMID- 24452203
TI  - Bone marrow stroma CD40 expression correlates with inflammatory mast cell
      infiltration and disease progression in splenic marginal zone lymphoma.
AB  - Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized
      by rather indolent clinical course. However, nearly one third of patients
      experience a rapidly progressive disease with a dismal outcome. Despite the
      characterization of clone genetics and the recognition of deregulated immunologic
      stimulation in the pathogenesis of SMZL, little is known about microenvironment
      dynamics and their potential biological influence on disease outcome. Here we
      investigate the effect of stroma-intrinsic features on SMZL disease progression
      by focusing on the microenvironment of the bone marrow (BM), which represents an
      elective disease localization endorsing diagnostic and prognostic relevance. We
      show that the quality of the BM stromal meshwork of SMZL infiltrates correlates
      with time to progression. In particular, we describe the unfavorable prognostic
      influence of dense CD40 expression by BM stromal cells, which involves the
      contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating
      SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal
      cells and mast cells populating the SMZL microenvironment finds correlation in
      p53(-/-) mice developing SMZL and contributes to the engendering of detrimental
      proinflammatory conditions. Our study highlights a dynamic interaction, playing
      between nonneoplastic elements within the SMZL niche, toward disease progression.

PMID- 24452204
TI  - Perinucleolar relocalization and nucleolin as crucial events in the
      transcriptional activation of key genes in mantle cell lymphoma.
AB  - In mantle cell lymphoma (MCL), one allele of the cyclin D1 (Ccnd1) gene is
      translocated from its normal localization on chromosome 11 to chromosome 14. This
      is considered as the crucial event in the transformation process of a normal
      naive B-cell; however, the actual molecular mechanism leading to Ccnd1 activation
      remains to be deciphered. Using a combination of three-dimensional and immuno
      fluorescence in situ hybridization experiments, the radial position of the 2
      Ccnd1 alleles was investigated in MCL-derived cell lines and malignant cells from
      affected patients. The translocated Ccnd1 allele was observed significantly more
      distant from the nuclear membrane than its nontranslocated counterpart, with a
      very high proportion of IgH-Ccnd1 chromosomal segments localized next to a
      nucleolus. These perinucleolar areas were found to contain active RNA polymerase
      II (PolII) clusters. Nucleoli are rich in nucleolin, a potent transcription
      factor that we found to bind sites within the Ccnd1 gene specifically in MCL
      cells and to activate Ccnd1 transcription. We propose that the Ccnd1
      transcriptional activation in MCL cells relates to the repositioning of the
      rearranged IgH-Ccnd1-carrying chromosomal segment in a nuclear territory with
      abundant nucleolin and active PolII molecules. Similar transforming events could
      occur in Burkitt and other B-cell lymphomas. 

PMID- 24452205
TI  - Sevoflurane postconditioning against cerebral ischemic neuronal injury is
      abolished in diet-induced obesity: role of brain mitochondrial KATP channels.
AB  - Obesity is associated with increased infarct volumes and adverse outcomes
      following ischemic stroke. However, its effect on anesthetic postconditioning
      induced neuroprotection has not been investigated. The present study examined the
      effect of sevoflurane postconditioning on focal ischemic brain injury in diet
      induced obesity. Sprague-Dawley rats were fed a high-fat diet (HF; 45% kcal as
      fat) for 12 weeks to develop obesity syndrome. Rats fed a low-fat diet (LF; 10%
      kcal as fat) served as controls. The HF or LF-fed rats were subjected to focal
      cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning
      was performed by exposure to sevoflurane for 15 min immediately at the onset of
      reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was
      analyzed by the administration of a selective inhibitor of 5-hydroxydecanoate (5
      HD) prior to sevoflurane postconditioning or by administration of diazoxide
      (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct
      volume, neurological score and motor coordination were evaluated 24 h after
      reperfusion. The HF-fed rats had larger infarct volumes, and lower neurological
      scores than the LF-fed rats and also failed to respond to neuroprotection by
      sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes
      and improved the neurological scores and motor coordination in the LF-fed rats.
      Pretreatment with 5-HD inhibited sevoflurane-induced neuroprotection in the LF
      fed rats, whereas it had no effect in the HF-fed rats. Molecular studies
      demonstrated that the expression of Kir6.2, a significant mitoKATP channel
      component, was reduced in the brains of the HF-fed rats compared with the LF-fed
      rats. The results of this study indicate that diet-induced obesity eliminates the
      ability of anesthetic sevoflurane postconditioning to protect the brain against
      cerebral ischemic neuronal injury, most likely due to an impaired brain mitoKATP
      channel.

PMID- 24452206
TI  - A new TRPV3 missense mutation in a patient with Olmsted syndrome and
      erythromelalgia.
AB  - IMPORTANCE: Olmsted syndrome (OS) is a rare keratinizing disorder characterized
      by excessive epidermal thickening of the palms and soles, with clinical and
      genetic heterogeneity. Approximately 50 cases have been reported, with the
      molecular basis described in only 9. Recently, TRPV3 (transient receptor
      potential vanilloid 3) mutations were identified in autosomal-dominant OS in 7
      sporadic cases and 1 familial case, whereas an MBTPS2 (membrane-bound
      transcription factor protease, site 2) mutation was reported in X-linked
      recessive OS. We report a new sporadic case of severe, atypical OS and its
      underlying genetic basis. OBSERVATIONS: Our patient is a young girl with severe
      nonmutilating (palmo)plantar keratoderma without periorificial keratotic plaques
      associated with intense acute flares of inflammation, itching, burning pain,
      vasodilatation, and redness of the extremities consistent with erythromelalgia.
      Whole exome sequencing of patient DNA identified a novel de novo heterozygous
      missense mutation within TRPV3, p.Leu673Phe, predicted to be damaging.
      CONCLUSIONS AND RELEVANCE: This case study further implicates TRPV3 in OS
      pathogenesis. In addition, previous reports of OS have not described
      erythromelalgia as a clinical feature. Its occurrence in our patient could be a
      chance event, but, if associated with OS, the features of erythromelalgia may
      expand the phenotypic spectrum of this rare syndrome.

PMID- 24452207
TI  - Lower-extremity electromyography measures during walking with ankle
      destabilization devices.
AB  - CONTEXT: Ankle-destabilization devices are rehabilitation tools that may improve
      neuromuscular control by increasing lower-extremity muscle activation. Their
      effects should be tested in healthy individuals before being implemented in
      rehabilitation programs. OBJECTIVE: To compare EMG activation of lower-extremity
      muscles during walking while wearing 2 different ankle-destabilization devices.
      DESIGN: Crossover. SETTING: Laboratory. PARTICIPANTS: 15 healthy young adults (5
      men, 10 women). INTERVENTION: Surface EMG activity was recorded from the anterior
      tibialis, peroneus longus, lateral gastrocnemius, rectus femoris, biceps femoris,
      and gluteus medius as subjects walked on a treadmill shod, with an ankle
      destabilization boot (ADB), and an ankle-destabilization sandal (ADS). MAIN
      OUTCOME MEASURES: Normalized amplitudes 100 ms before and 200 ms after initial
      heel contact, time of onset activation relative to initial contact, and percent
      of activation time across the stride cycle were calculated for each muscle in
      each condition. RESULTS: The precontact amplitudes of the peroneus longus and
      lateral gastrocnemius and the postcontact amplitudes of the lateral gastrocnemius
      were significantly greater in the ADB and ADS conditions. In the ADB condition,
      the rectus femoris and biceps femoris postcontact amplitudes were significantly
      greater than shod. The peroneus longus and lateral gastrocnemius were activated
      significantly earlier, and the anterior tibialis, lateral gastrocnemius, and
      rectus femoris were activated significantly longer across the stride cycle in the
      ADB and the ADS conditions. In addition, the peroneus longus was activated
      significantly longer in the ADB condition when compared with shod. CONCLUSIONS:
      Both ankle-destabilization devices caused an alteration in muscle activity during
      walking, which may be favorable to an injured patient. Therefore, implementing
      these devices in rehabilitation programs may be beneficial to improving
      neuromuscular control.

PMID- 24452208
TI  - Predicting transepithelial phototherapeutic keratectomy outcomes using Fourier
      domain optical coherence tomography.
AB  - PURPOSE: The aim of this study was to use Fourier domain optical coherence
      tomography to predict transepithelial phototherapeutic keratectomy outcomes.
      METHODS: This is a prospective case series. Subjects with anterior stromal
      corneal opacities underwent an excimer laser phototherapeutic keratectomy (PTK)
      combined with a photorefractive keratectomy using the VISX S4 excimer laser (AMO,
      Inc, Santa Ana, CA). Preoperative and postoperative Fourier domain optical
      coherence tomography images were used to develop a simulation algorithm to
      predict treatment outcomes. Main outcome measures included preoperative and
      postoperative uncorrected distance visual acuities and corrected distance visual
      acuity. RESULTS: Nine eyes of 8 patients were treated. The nominal ablation depth
      was 75 to 177 MUm centrally and 62 to 185 MUm peripherally. Measured PTK ablation
      depths were 20% higher centrally and 26% higher peripherally, compared with those
      for laser settings. Postoperatively, the mean uncorrected distance visual acuity
      was 20/41 (range, 20/25-20/80) compared with 20/103 (range, 20/60-20/400)
      preoperatively. The mean corrected distance visual acuity was 20/29 (range, 20/15
      20/60) compared with 20/45 (range, 20/30-20/80) preoperatively. The MRSE was
      +1.38 +/- 2.37 diopters (D) compared with -2.59 +/- 2.83 D (mean +/- SD). The
      mean astigmatism magnitude was 1.14 +/- 0.83 D compared with 1.40 +/- 1.18 D
      preoperatively. Postoperative MRSE correlated strongly with ablation settings,
      central and peripheral epithelial thickness (r = 0.99, P < 0.00001). Central
      islands remained difficult to predict and limited visual outcomes in some cases.
      CONCLUSIONS: Optical coherence tomography measurements of opacity depth and 3
      dimensional ablation simulation provide valuable guidance in PTK planning. Post
      PTK refraction may be predicted with a regression formula that uses epithelial
      thickness measurements obtained by optical coherence tomography. The laser
      ablation rates described in this study apply only to the VISX laser.

PMID- 24452209
TI  - Outcomes of corneal collagen crosslinking in pseudophakic bullous keratopathy.
AB  - PURPOSE: The aim was to evaluate the outcomes of corneal collagen crosslinking
      (CXL) in symptomatic pseudophakic bullous keratopathy (PBK). METHODS: In a
      retrospective noncomparative, interventional case series, we reviewed the records
      of 50 eyes (50 patients) with symptomatic PBK who underwent CXL. Central corneal
      thickness (CCT), pain score, best corrected visual acuity (BCVA), and corneal
      transparency were recorded at baseline; at day 7, day 15; and 1, 3, and 6 months
      after the CXL. RESULTS: The mean pain score decreased from 8.1 +/- 0.6 at
      presentation to 2.1 +/- 0.7 on day 7 (P = 0.0001). A subsequent regression was
      seen in pain scores over 6 months (5.3 +/- 1.5). The mean CCT decreased from a
      preoperative value of 724.8 +/- 78.4 to 694.9 +/- 77.9 MUm by the end of the
      first month (P = 0.0001). The CCT remained stable at subsequent follow-up. The
      BCVA improved from logarithm of the minimum angle of resolution (log MAR) 2.0 +/-
      0.5 preoperatively to log MAR 1.8 +/- 0.5 by the end of the first month (P =
      0.001). The subsequent follow-up showed a progressive deterioration in the BCVA
      to the preoperative levels at 6 months. Corneal bullae recurred in 44% (22 eyes)
      at 6 months after an initial disappearance. A significant improvement in the BCVA
      and a lack of recurrence of bullae were significantly associated with a thinner
      CCT on presentation. CONCLUSIONS: CXL in symptomatic PBK temporarily improves
      pain without providing long-term improvement in the BCVA. Case selection is
      important with more effect seen in patients with a thinner CCT at presentation.

PMID- 24452210
TI  - Inhibition of pathological corneal neovascularization by a small peptide derived
      from human apolipoprotein (a) Kringle V.
AB  - PURPOSE: The aim of this study was to evaluate the antiangiogenic activity of
      AU6, a novel 6-amino acid peptide derived from Kringle V of human apolipoprotein
      (a). METHODS: RF/6A rhesus macaque choroid endothelial cells were used for in
      vitro studies. MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium, inner salt] assays and modified Boyden chamber and
      Matrigel assays were used to evaluate the inhibitory effect of AU6 on vascular
      endothelial growth factor (VEGF)-stimulated endothelial cell functions, including
      cell proliferation, migration, and tube formation. The chick chorioallantoic
      membrane model, micropocket corneal neovascularization (CNV) model, and alkali
      burn CNV model were evaluated in vivo. Bevacizumab (Avastin), the VEGF
      neutralizing antibody, and a scrambled peptide (AU6s) were used as positive and
      negative controls, respectively. RESULTS: AU6 inhibited VEGF-induced RF/6A cell
      migration, proliferation, and tube formation. It also reduced pathological
      neovascularization in the chorioallantoic membrane model and in the 2 CNV models,
      that is, the mouse corneal micropocket model and the rat cornea alkali burn
      model. CONCLUSIONS: AU6 effectively inhibited pathogenic CNV. This novel peptide
      shows potential as a new treatment for ocular neovascularization.

PMID- 24452211
TI  - Comparison of sulfur hexafluoride and air for donor attachment in Descemet
      stripping endothelial keratoplasty in patients with pseudophakic bullous
      keratopathy.
AB  - PURPOSE: The aim of this study was to evaluate the clinical efficacy and safety
      of sulfur hexafluoride (SF6) as a tamponading agent after donor placement during
      Descemet stripping endothelial keratoplasty (DSEK) surgery and to compare the
      outcomes with those of air. METHODS: Forty-four eyes of 44 consecutive patients
      who underwent DSEK were included in the study. Air was used in 22 eyes of 22
      patients (air group), and SF6 was used in 22 eyes of 22 patients (SF6 group) to
      attach the donor lenticule. The complications, corrected visual acuity (CVA), and
      the endothelial cell density (ECD) results were compared between these 2 groups.
      RESULTS: Six eyes had graft dislocation in the air group that underwent
      successful rebubbling on postoperative day 1. There was no graft dislocation in
      the SF6 group. There was no other complication observed in both the groups. The
      mean increase in the CVA was 1.09 +/- 0.36 logarithm of the minimum angle of
      resolution in the air group, whereas it was 0.80 +/- 0.57 logarithm of the
      minimum angle of resolution in the SF6 group. The mean increase in the CVA was
      not statistically different between the 2 groups (P = 0.060). Compared with the
      mean ECD in donor grafts, the mean decrease in the ECD was 222 +/- 86 (44%) cells
      per square millimeter in the air group and 178 +/- 52 (39%) cells per square
      millimeter in the SF6 group at the 1-year follow-up. The mean decrease in the ECD
      was statistically significantly higher in the air group compared with that in the
      SF6 group (P = 0.049). CONCLUSIONS: SF6 is comparable to air for attaching the
      donor graft as a tamponading agent in DSEK surgery.

PMID- 24452212
TI  - DSAEK: practical approach to choose the microkeratome head on the basis of donor
      cornea pachymetry.
AB  - PURPOSE: The aim of this study was to supply data on the relationship between
      Descemet stripping automated endothelial keratoplasty (DSAEK) graft thickness and
      its effects on visual acuity (VA), pace of visual recovery, endothelial cell
      densities (ECDs), and surgical complications. We additionally provide an approach
      for choosing the microkeratome blade thickness when multiple patients are
      scheduled for DSAEK. METHODS: This is a retrospective analysis of all DSAEK
      procedures performed at our institute from January 2011 to December 2012. The VA
      was assessed at all postop visits. The ECD was assessed at 6 and 12 months
      postoperatively. An algorithm based on donor cornea pachymetry was used to assist
      in the choice of a microkeratome blade either 350 or 400 MUm thick. Two groups
      were created on the basis of the microkeratome blade chosen. Outcomes were given
      per treatment group. RESULTS: One hundred two consecutive DSAEK procedures were
      performed; 60 grafts were prepared with the 350-MUm blade and 39 with the 400-MUm
      blade. Baseline characteristics did not differ materially. Grafts dissected using
      the 350-MUm knife were significantly thicker than the grafts dissected with the
      400-MUm blade, with values of 257 +/- 47 MUm and 222 +/- 33 MUm, respectively (P
      = 0.01). The pace of visual recovery, VA at maximum follow-up, and ECD did not
      differ significantly between groups. Surgical complications were evenly
      distributed over both groups. CONCLUSIONS: This study indicates that using
      neither the 350-MUm nor 400-MUm microkeratome blade for the DSAEK altered the
      outcomes in terms of VA, ECD, and surgical complications. The algorithm presented
      in this study is helpful in equally distributing benefits from thinner grafting
      for all DSAEK-operated patients.

PMID- 24452213
TI  - Treatment of ocular rosacea with once-daily low-dose doxycycline.
AB  - PURPOSE: The aim of this study was to determine the efficacy of once-daily
      systemic treatment of ocular rosacea with a slow-release form of 40 mg of
      doxycycline. METHODS: Fifteen patients with ocular rosacea were enrolled between
      February 2010 and October 2012 in a retrospective observational case series.
      Patient complaints and clinical findings including blepharitis with
      telangiectasia and meibomian gland dysfunction, conjunctival redness, and
      fluorescein staining of the cornea were evaluated. The ocular manifestations were
      scored as follows: 0-absent, 1-mild, 2-moderate, and 3-severe. All measurements
      were repeated at the 6-week follow-up visit. The mean duration of treatment was 8
      months (range, 5-12 months), and the mean duration of the follow-up was 9 months
      (range, 6-17 months). RESULTS: At the baseline visit, 73.3% of the patients had
      severe complaints, and 80% had severe blepharitis despite topical therapy with
      artificial tears and eyelid hygiene. After 12 weeks of systemic therapy, severe
      complaints and blepharitis strongly improved and were seen in only 13.3% and 20%
      of the patients (P = 0.01). Follow-up investigations 6 to 17 months after
      discontinuation of the treatment showed further significant improvement of
      complaints (absent or mild in 66.7% and 20% of the patients, respectively) and
      blepharitis (absent or mild in 26.7% and 60% of the patients, respectively). One
      patient had a mild stomach ache so that therapy was shortened to 5 months.
      CONCLUSIONS: An antiinflammatory dose of slow-release doxycycline 40 mg given
      daily may be an effective and safe therapy of ocular rosacea.

PMID- 24452214
TI  - Estimation of the central corneal power in keratoconus: theoretical and clinical
      assessment of the error of the keratometric approach.
AB  - PURPOSE: The aim of this study was to analyze theoretically the errors in the
      central corneal power calculation in eyes with keratoconus when a keratometric
      index (nk) is used and to clinically confirm the errors induced by this approach.
      METHODS: Differences (DeltaPc) between central corneal power estimation with the
      classical nk (Pk) and with the Gaussian equation ((Equation is included in full
      text article.)) in eyes with keratoconus were simulated and evaluated
      theoretically, considering the potential range of variation of the central radius
      of curvature of the anterior (r1c) and posterior (r2c) corneal surfaces. Further,
      these differences were also studied in a clinical sample including 44 keratoconic
      eyes (27 patients, age range: 14-73 years). The clinical agreement between Pk and
      (Equation is included in full-text article.)(true net power) obtained with a
      Scheimpflug photography-based topographer was evaluated in such eyes. RESULTS:
      For nk = 1.3375, an overestimation was observed in most cases in the theoretical
      simulations, with DeltaPc ranging from an underestimation of -0.1 diopters (D)
      (r1c = 7.9 mm and r2c = 8.2 mm) to an overestimation of 4.3 D (r1c = 4.7 mm and
      r2c = 3.1 mm). Clinically, Pk always overestimated the (Equation is included in
      full-text article.)given by the topography system in a range between 0.5 and 2.5
      D (P < 0.01). The mean clinical DeltaPc was 1.48 D, with limits of agreement of
      0.71 and 2.25 D. A very strong statistically significant correlation was found
      between DeltaPc and r2c (r = -0.93, P < 0.01). CONCLUSIONS: The use of a single
      value for nk for the calculation of corneal power is imprecise in keratoconus and
      can lead to significant clinical errors.

PMID- 24452215
TI  - Descemet membrane endothelial keratoplasty donor preparation: navigating
      challenges and improving efficiency.
AB  - PURPOSE: The aim of this study was to describe the challenges in Descemet
      membrane endothelial keratoplasty (DMEK) donor preparations and provide new
      strategies to achieve success. METHODS: A series of 263 consecutive DMEK
      preparation attempts by a novice surgeon during a corneal fellowship are
      described. In all cases, the Descemet membrane (DM) and the endothelium were
      peeled off from the donor cornea while it was submerged in corneal storage
      medium. RESULTS: The success rate of preparing DMEK tissue was 99%. Three donor
      preparations of 263 (1.1%) could not be completed successfully because spots of
      strong adherence between the DM and the stroma caused multiple horseshoe-shaped
      tears (HST) to form in the DM. Lamellar splitting of the DM ("partial thickness
      HST") preceded the formation of most HSTs. At least 1 HST occurred in 13% of
      donor preparations. In donor pairs (right and left corneas of 1 individual
      donor), if 1 cornea had any HSTs, there was a 60% chance that the contralateral
      cornea would have at least 1 HST. If 1 cornea had multiple HSTs, there was an 80%
      chance that the contralateral cornea would have at least 1 HST. Noting this
      trend, 3 donor corneas were returned to the eye bank unopened for other uses
      after their mates had multiple HSTs. CONCLUSIONS: With appropriate techniques,
      DMEK donor preparation can be highly successful, even for a novice surgeon. When
      a donor develops multiple HSTs, we recommend not using the mate for DMEK because
      of a higher risk of encountering a preparation difficulty.

PMID- 24452216
TI  - Impact of Valsalva maneuver on corneal morphology and anterior chamber
      parameters.
AB  - PURPOSE: Our aim was to examine the influence of the Valsalva maneuver (VM) on
      corneal morphology and anterior chamber parameters. METHODS: This prospective
      observational study included 35 eyes of 35 healthy volunteers. One of the eyes of
      each subject was selected randomly. The keratometry (K), pachymetry, corneal
      volume, iridocorneal angle, anterior chamber depth, anterior chamber volume, and
      corneal wave front measurements (high-order aberration, low-order aberration,
      total root mean square) were performed with the Pentacam HR (Oculus, Wetzlar,
      Germany). RESULTS: The subjects were aged between 22 and 41 years. There were 24
      men (69%) and 11 women (31%). The VM did not have any significant influence on K
      flat and K-average values (P > 0.05), but it decreased K-steep values
      significantly (P = 0.006). The VM did not have any significant impact on low
      order aberrations and total root mean square parameters (P > 0.05), but it
      increased high-order aberrations significantly (P = 0.008). The central corneal
      thickness and corneal volume decreased significantly during the VM (P < 0.05).
      The iridocorneal angle, anterior chamber depth, and anterior chamber volume
      decreased markedly during the VM (P < 0.001). CONCLUSIONS: The VM has some
      influence on corneal morphology and anterior chamber parameters, so that it
      should be considered during anterior segment examinations and operations.

PMID- 24452217
TI  - Novel approach for the treatment of corneal ectasia in a graft.
AB  - PURPOSE: The aim of this study was to report the use of novel masking agents
      during an anterior lamellar keratoplasty performed using a femtosecond laser in a
      patient with corneal ectasia that was consistent with recurrent keratoconus.
      METHODS: This is a case report. RESULTS: A 55-year-old man, with a 23-year status
      after penetrating keratoplasty for keratoconus, presented with a chief complaint
      of ocular discomfort in the right eye. On slit-lamp examination, the physician
      estimated 70% to 80% inferior thinning at the graft-host interface with inferior
      corneal neovascularization. Because of the high risk of developing corneal
      perforation and the patient's desire to minimize visual recovery time, anterior
      lamellar keratoplasty was chosen. To minimize the risk of perforation during
      femtosecond dissection of the anterior lamellar bed, gentian violet and
      cyanoacrylate glue were used in the area of thinning as masking agents.
      CONCLUSIONS: This represents the first documented use of gentian violet and
      cyanoacrylate glue as double masking agents to defocus the femtosecond laser
      raster pass during keratoplasty.

PMID- 24452218
TI  - Induction of neoplasia after deep anterior lamellar keratoplasty in a CXL-treated
      cornea.
AB  - PURPOSE: Corneal collagen crosslinking (CXL) with ultraviolet-A energy plus
      riboflavin has become a ubiquitous treatment in early keratoconus, although its
      long-term safety is unknown. We describe severe sequelae in a CXL-treated patient
      after he underwent a standard deep anterior lamellar keratoplasty procedure.
      METHODS: In April 2009, a healthy 49-year-old male patient (R.H.) underwent
      bilateral CXL according to the Dresden protocol for progressive keratoconus stage
      3. The best-corrected visual acuity did not improve over 20/100 within a
      postoperative period of 2 years, and contact lenses were not tolerated.
      Consequently, a unilateral deep anterior lamellar keratoplasty was performed, to
      transplant an 8-mm fully epithelialized button onto an 8-mm bed with a bared
      Descemet membrane (surgeon: J.H.K.). RESULTS: The postoperative healing course
      was unusually disturbed. Sutures pulled through the recipient tissue, which
      required suture replacement. Portions of the epithelium sloughed off repeatedly,
      and bulky regrowth displayed no attachment to the Bowman membrane. Within the
      first weeks, the transplant became cloudy. Two biopsies were removed from the
      limbus area and submitted to independent histopathological laboratories, both of
      which diagnosed the condition as epithelial neoplasia. Pathology tests indicated
      conjunctival intraepithelial neoplasia, the preliminary stage of invasive
      squamous cell carcinoma, in the keratocyte-voided bed of the recipient.
      CONCLUSIONS: This case suggests that CXL might hamper the ocular healing process
      and, combined with subsequent corneal surgery, could potentially initiate
      neoplasia. Further investigation is warranted to determine the safety of the
      combination of ultraviolet-A/riboflavin treatment and subsequent corneal tissue
      transplantation.

PMID- 24452219
TI  - Modification of the Miyake-Apple technique for simultaneous anterior and
      posterior video imaging of wet laboratory-based corneal surgery.
AB  - PURPOSE: The aim of this study was to describe a modification of the Miyake-Apple
      posterior video analysis for the simultaneous visualization of the anterior and
      posterior corneal surfaces during wet laboratory-based deep anterior lamellar
      keratoplasty (DALK). METHODS: A human donor corneoscleral button was affixed to a
      microscope slide and placed onto a custom-made mounting box. A big bubble DALK
      was performed on the cornea in the wet laboratory. An 11-diopter intraocular lens
      was positioned over the aperture of the back camera of an iPhone. This served to
      video record the posterior view of the corneoscleral button during the big bubble
      formation. An overhead operating microscope with an attached video camcorder
      recorded the anterior view during the surgery. RESULTS: The anterior and
      posterior views of the wet laboratory-based DALK surgery were simultaneously
      captured and edited using video editing software. The formation of the big bubble
      can be studied. CONCLUSIONS: This video recording camera system has the potential
      to act as a valuable research and teaching tool in corneal lamellar surgery,
      especially in the behavior of the big bubble formation in DALK.

PMID- 24452220
TI  - Descemet membrane detachment after heavy silicone oil removal from the anterior
      chamber.
AB  - PURPOSE: The aim of this study was to report a case of a central Descemet
      membrane detachment after heavy silicone oil removal from the anterior chamber.
      METHODS: This is a case report of a patient operated with scleral buckling and
      heavy silicone oil implantation for recurrent retinal detachment. In the
      patient's follow-up examination, silicone oil was found to completely fill the
      anterior chamber. He underwent silicone extraction through a paracentesis from
      the anterior chamber. Immediately after the surgery, a central Descemet membrane
      detachment combined with corneal edema was identified on slit-lamp examination,
      and confirmed by anterior segment optical coherence tomography. The detached
      Descemet membrane was tamponaded successfully with the air bubble injection
      technique. RESULTS: Four days later, the patient's cornea appeared to be clear,
      and the Descemet membrane was found to be attached to the corneal stroma with no
      presence of silicone oil in the anterior chamber. CONCLUSIONS: Descemet membrane
      detachment is a possible and rare complication that occurs after heavy silicone
      oil removal from the anterior chamber.

PMID- 24452222
TI  - Heart failure and COPD: time to SHIFT?

PMID- 24452221
TI  - Formation mechanism of chalcogenide nanocrystals confined inside genetically
      engineered virus-like particles.
AB  - Engineered virus-like particles (VLP) are attractive for fabricating
      nanostructured materials for applications in diverse areas such as catalysis,
      drug delivery, biomedicine, composites, etc. Basic understanding of the
      interaction between the inorganic guest and biomolecular host is thus important
      for the controlled synthesis of inorganic nanoparticles inside VLP and rational
      assembly of ordered VLP-based hierarchical nanostructures. We have investigated
      in detail the formation mechanism and growth kinetics of semiconducting
      nanocrystals confined inside genetically engineered bacteriophage P22 VLP using
      semiconducting CdS as a prototypical example. The selective nucleation and growth
      of CdS at the engineered sites is found to be uniform during the early stage,
      followed by a more stochastic growth process. Furthermore, kinetic studies reveal
      that the presence of an engineered biotemplate helps in significantly retarding
      the reaction rate. These findings provide guidance for the controlled synthesis
      of a wide range of other inorganic materials confined inside VLP, and are of
      practical importance for the rational design of VLP-based hierarchical
      nanostuctures. 

PMID- 24452224
TI  - Obstructive sleep apnea and risk of stroke: a meta-analysis of prospective
      studies.

PMID- 24452223
TI  - Basal functional status predicts three-month mortality after a heart failure
      hospitalization in elderly patients - the prospective RICA study.
AB  - BACKGROUND: Many elderly heart failure (HF) patients show some degree of
      functional impairment. The study aim was to evaluate the functional status of
      oldest-old cohort of patients hospitalized with a diagnosis of decompensated
      (HF), and to analyze whether preadmission functional status predicts risk of 3
      month mortality. METHODS: We analyzed 1431 elderly (>= 75 years) patients
      prospectively included in the Spanish National Registry on HF (RICA). We added
      Barthel Index (BI) to the usual HF patient assessment to measure patients'
      functional status, and we evaluated the relationship between preadmission BI
      values and 3-month mortality. RESULTS: The mean age of patients was 82.3 (4.6)
      years. Patients' mean preadmission BI score was 81.3 (21.5); 802 patients (55.9%)
      had BI scores <61. Multivariate analysis confirmed an independent association
      between poor preadmission BI and older age, female sex, higher comorbidity,
      cognitive impairment, previous institutionalization, worse New York Heart
      Association (NYHA) functional class and lack of beta-blocker use. A total of 210
      patients died (14.7%) after 3 months of follow-up. Cox multivariate analyses
      found that higher preadmission BI is correlated with reduced all-cause, 3-month
      postdischarge mortality [hazard ratio (HR) 0.981; CI95% 0.975-0.986, p<0.001].
      Other variables independently associated with 3-month mortality were male sex,
      lower body mass index, lower systolic blood pressure, a diagnosis of diabetes and
      chronic kidney disease, worse NYHA class and not receiving treatment with beta
      blockers. CONCLUSIONS: Severe functional disability is present among more than
      half of older patients admitted because of a HF decompensation. For this
      population, preadmission BI is a strong predictor of short-term mortality.

PMID- 24452225
TI  - Spinal angle and foot pressure during cardiac electrophysiological procedures.

PMID- 24452226
TI  - How did Haly Abbas look at the cardiovascular system?
AB  - Persian scholars, especially those who lived during the Golden Age of Islamic
      Medicine (9th-12th century AD), made significant contributions to the healing
      arts and secured a place of honor for themselves in the history of this science.
      Abu l-Hasan Ali ibn al-'Abbas al-Majusi Ahvazi (? 930-994AD), with the Latinized
      name of Haly Abbas, was a scientist from this part of the world who contributed
      to the advancement of medicine. He is the author of Kamil al-Sina'ah al-Tibbiyah
      (The Perfect Book of the Art of Medicine), also commonly known as al-Kitab al
      Maliki (The Royal Book), a medical encyclopedia renowned for its systematic and
      precise content. This textbook covers a wide variety of medical issues, among
      them topics related to the science of cardiology. This paper reviews the main
      points of Haly Abbas' knowledge of the cardiovascular system, of which little has
      been written until now.

PMID- 24452227
TI  - 320-slice CT-based finding of aortic wall tissue invasion into left-main coronary
      artery does not have relationship with coronary risk factors and coronary
      arteriosclerosis and stenosis.

PMID- 24452228
TI  - Network correlates of sexual health advice seeking and substance use among
      members of the Los Angeles House and Ball communities.
AB  - House and Ball communities (HBCs), represent a prime context for human
      immunodeficiency virus prevention with African American young men who have sex
      with men and transgender persons. This study sought to understand the composition
      and function of social support and sexual networks of HBC members in Los Angeles,
      California (N = 263). Participants were recruited using venue-based sampling and
      asked to report on sexual health advice seeking, alcohol use and illicit
      substance use. Participants were more likely to seek sexual health advice from
      social support network members compared with sexual network members [odds ratio
      (OR): 2.50, P < 0.001]. HBC members were more likely to get drunk (OR: 1.57; P <
      0.05) and use illicit substances (OR: 1.87; P < 0.10) with House members and
      sexual network members compared with non-House members and social support network
      members. Health promotion programs tailored for the HBC should encourage open
      communication regarding sexual health; these interventions must include
      information about the role of substance use in sexual risk taking. 

PMID- 24452229
TI  - The use of message framing to promote sexual risk reduction in young adolescents:
      a pilot exploratory study.
AB  - Few studies have explored the application of message framing to promote health
      behaviors in adolescents. In this exploratory study, we examined young
      adolescents' selection of gain- versus loss-framed images and messages when
      designing an HIV-prevention intervention to promote delayed sexual initiation.
      Twenty-six adolescents (aged 10-14 years) participated in six focus groups and
      created and discussed posters to persuade their peers to delay the initiation of
      sexual activity. Focus groups were audio-recorded and transcribed. A five-person
      multidisciplinary team analyzed the posters and focus group transcripts using
      thematic analysis. The majority of the posters (18/26, 69%) contained both gain-
      and loss-framed content. Of the 93/170 (56%) images and messages with framing,
      similar proportions were gain- (48/93, 52%) and loss-framed (45/93, 48%). Most
      gain-framed content (23/48, 48%) focused on academic achievement, whereas loss
      framed content focused on pregnancy (20/45, 44%) and HIV/AIDS (14/45, 31%). These
      preliminary data suggest that young adolescents may prefer a combination of gain-
      and loss-framing in health materials to promote reduction in sexual risk
      behaviors. 

PMID- 24452230
TI  - The vitamin D RDA for African American adults: higher than that for white
      persons?

PMID- 24452231
TI  - Infant formula and infant nutrition: bioactive proteins of human milk and
      implications for composition of infant formulas.
AB  - Human milk contains an abundance of biologically active components that are
      highly likely to contribute to the short- and long-term benefits of
      breastfeeding. Many of these components are proteins; this article describes some
      of these proteins, such as alpha-lactalbumin, lactoferrin, osteopontin, and milk
      fat globule membrane proteins. The possibility of adding their bovine
      counterparts to infant formula is discussed as well as the implications for
      infant health and development. An important consideration when adding bioactive
      proteins to infant formula is that the total protein content of formula needs to
      be reduced, because formula-fed infants have significantly higher concentrations
      of serum amino acids, insulin, and blood urea nitrogen than do breastfed infants.
      When reducing the protein content of formula, the amino acid composition of the
      formula protein becomes important because serum concentrations of the essential
      amino acids should not be lower than those in breastfed infants. Both the supply
      of essential amino acids and the bioactivities of milk proteins are dependent on
      their digestibility: some proteins act only in intact form, others act in the
      form of larger or small peptides formed during digestion, and some are completely
      digested and serve as a source of amino acids. The purity of the proteins or
      protein fractions, potential contaminants of the proteins (such as
      lipopolysaccharide), as well as the degree of heat processing used during their
      isolation also need to be considered. It is likely that there will be more
      bioactive components added to infant formulas in the near future, but guidelines
      on how to assess their bioactivities in vitro, in animal models, and in clinical
      studies need to be established. The extent of testing needed is likely going to
      depend on the degree of complexity of the components and their bioequivalence
      with the human compounds whose effects they are intended to mimic. 

PMID- 24452232
TI  - Data needs for B-24 and beyond: NHANES data relevant for nutrition surveillance
      of infants and young children.
AB  - The period from birth to 24 mo (B-24) is a critical phase in which nutrient
      requirements for growth and development are high and several transitions in food
      consumption practices occur. A few large-scale national studies (eg, the Feeding
      Infants and Toddlers Study and Infant Feeding Practices Study) offer important
      insights into infant feeding practices and food consumption patterns in young
      children in the United States. The NHANES collects comprehensive cross-sectional
      data on the nutrition and health of Americans including infants and toddlers.
      This article describes the NHANES program and data from NHANES 1999-2010 on young
      children that are relevant for the B-24 Project. NHANES is a nationally
      representative survey of the noninstitutionalized US population that combines
      personal interviews with standardized physical examination and measurements via
      mobile examination centers. Data on infant feeding practices (breastfeeding and
      timing of introduction and nature of complementary foods), dietary intake (two 24
      h recalls), and nutrient supplements are collected. Data on demographic
      characteristics, anthropometric measurements, biomarkers of nutrient status, food
      security, and participation in federal nutrition programs are also available.
      Data can be accessed online, downloaded, and pooled over several survey cycles,
      allowing examination of infant feeding practices, food and nutrient intakes, and
      nutritional status of Americans <2 y old. Subgroup analyses by race-ethnicity and
      income status are also possible. NHANES responds to evolving data needs, as
      feasible, in the context of the survey design, research priorities, and funding.
      It offers a vehicle for potentially gathering additional data on children <2 y to
      address the objectives of the B-24 Project in the future. 

PMID- 24452233
TI  - Protein needs early in life and long-term health.
AB  - The objective of this review was to summarize selected health aspects of protein
      intake during the first 2 y of life. During this period there is a marked
      increase in protein intake from an intake of ~ 5% of energy from protein (PE%) in
      an exclusively breastfed infant to ~ 15 PE% when complementary foods have been
      introduced. At this age, mean protein intake is ~ 3 times as high as the
      physiologic requirement, but some children receive 4-5 times their physiologic
      requirement. Protein from cow milk constitutes a main part of protein intake in
      toddlers and seems to have a specific effect on insulin-like growth factor I
      concentrations and growth. Meat has a high protein content, but the small amounts
      of meat needed to ensure good iron status have less impact on total protein
      intake. The difference in protein intake between breastfed and formula-fed
      infants is likely to play a role in the difference between breastfed and formula
      fed infants. There is emerging evidence that high protein intake during the first
      2 y of life is a risk factor for later development of overweight and obesity. It
      therefore seems prudent to avoid a high protein intake during the first 2 y of
      life. This could be accomplished by decreasing the upper allowable limit of the
      protein content of infant formulas for the first year of life and limiting the
      intake of cow milk in the second year of life.

PMID- 24452234
TI  - USDA Nutrition Evidence Library: methodology used to identify topics and develop
      systematic review questions for the birth-to-24-mo population.
AB  - The USDA's Nutrition Evidence Library (NEL) specializes in conducting food- and
      nutrition-related systematic reviews that are used to inform federal government
      decision making. To ensure the utility of NEL systematic reviews, the most
      relevant topics must be addressed, questions must be clearly focused and
      appropriate in scope, and review frameworks must reflect the state of the
      science. Identifying the optimal topics and questions requires input from a
      variety of stakeholders, including scientists with technical expertise, as well
      as government policy and program leaders. The objective of this article is to
      describe the rationale and NEL methodology for identifying topics and developing
      systematic review questions implemented as part of the "Evaluating the evidence
      base to support the inclusion of infants and children from birth to 24 months of
      age in the Dietary Guidelines for Americans--the B-24 Project." This is the first
      phase of a larger project designed to develop dietary guidance for the birth to
      24-mo population in the United States.

PMID- 24452235
TI  - Learning to eat: birth to age 2 y.
AB  - During the first 2 y of life, development is rapid and includes dramatic changes
      in eating behavior. Individual patterns of food preferences and eating behaviors
      emerge and differ depending on the foods offered and on the contexts of feeding
      during this early period of dietary transition. In this review, we discuss
      evidence on ways in which early learning influences food preferences and eating
      behavior, which, in turn, shape differences in dietary patterns, growth, and
      health. Although the evidence reviewed indicates that this early period of
      transition provides opportunities to influence children's developing intake
      patterns, there is no consistent, evidence-based guidance for caregivers who are
      feeding infants and toddlers; the current Dietary Guidelines are intended to
      apply to Americans over the age of 2 y. At present, the evidence base with regard
      to how and what children learn about food and eating behavior during these first
      years is limited. Before developing guidance for parents and caregivers, more
      scholarship and research is necessary to understand how infants and toddlers
      develop the food preferences and self-regulatory processes necessary to promote
      healthy growth, particularly in today's environment. By the time they reach 2 y
      of age, children have essentially completed the transition to "table foods" and
      are consuming diets similar to those of other family members. This article
      discusses parenting and feeding approaches that may facilitate or impede the
      development of self-regulation of intake and the acceptance of a variety of foods
      and flavors necessary for a healthy diet. We review the limited evidence on how
      traditional feeding practices, familiarization, associative learning, and
      observational learning affect the development of eating behavior in the context
      of the current food environment. Areas for future research that could inform the
      development of anticipatory guidance for parents and caregivers responsible for
      the care and feeding of young children are identified. 

PMID- 24452236
TI  - Food-addiction scale measurement in 2 cohorts of middle-aged and older women.
AB  - BACKGROUND: Excess weight is a major threat to public health. An addiction-like
      tendency toward certain foods may contribute to overeating. OBJECTIVE: We aimed
      to describe the prevalence and associated characteristics in relation to a food
      addiction scale in middle-aged and older women. DESIGN: We examined the
      prevalence and associated characteristics of a food-addiction scale measure in a
      cross-sectional analysis of 134,175 women participating in 2 ongoing prospective
      cohort studies of US nurses. RESULTS: Overall, 7839 (5.8%) of the women surveyed
      met the criteria for food addiction measured by using the modified Yale Food
      Addiction Scale. The prevalence of food addiction was 8.4% in the younger cohort
      of women aged 45-64 y and 2.7% in the older cohort of women aged 62-88 y. In the
      multivariate model, body mass index (BMI; in kg/m2) >= 35.0 (compared with 18.5
      22.9) was associated with food addiction, a prevalence ratio (PR) of 15.83 (95%
      CI: 12.58, 19.91) in the younger cohort of women, and a PR of 18.41 (95% CI:
      11.63, 29.14) in the older cohort of women. Several other demographic
      characteristics and other factors were associated with the food-addiction measure
      in both cohorts of women. CONCLUSIONS: To our knowledge, for the first time in a
      large, US-based population of women, we documented the prevalence of food
      addiction by using a novel measurement scale in middle-aged and older women. The
      results may provide insight into the strong association between behavioral
      attributes of food consumption and the development of obesity.

PMID- 24452238
TI  - Flavonoid-rich fruit and vegetables improve microvascular reactivity and
      inflammatory status in men at risk of cardiovascular disease--FLAVURS: a
      randomized controlled trial.
AB  - BACKGROUND: Observed associations between increased fruit and vegetable (F&V)
      consumption, particularly those F&Vs that are rich in flavonoids, and vascular
      health improvements require confirmation in adequately powered randomized
      controlled trials. OBJECTIVE: This study was designed to measure the dose
      response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual
      F&V intakes and vascular function and other cardiovascular disease (CVD) risk
      indicators. DESIGN: A single-blind, dose-dependent, parallel randomized
      controlled dietary intervention study was conducted. Male and female low-F&V
      consumers who had a >= 1.5-fold increased risk of CVD (n = 174) were randomly
      assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V
      amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every
      6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with
      iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis
      (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO),
      vascular function, and inflammation were determined at baseline and at 6, 12, and
      18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent
      microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C
      reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion
      molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO
      (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase
      in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated
      increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO
      (P = 0.0299) in the control group. CONCLUSION: These data support recommendations
      to increase F&V intake to >= 6 portions daily, with additional benefit from F&Vs
      that are rich in flavonoids, particularly in men with an increased risk of CVD.

PMID- 24452237
TI  - Ontogeny of taste preferences: basic biology and implications for health.
AB  - Health initiatives address childhood obesity in part by encouraging good
      nutrition early in life. This review highlights the science that shows that
      children naturally prefer higher levels of sweet and salty tastes and reject
      lower levels of bitter tastes than do adults. Thus, their basic biology does not
      predispose them to favor the recommended low-sugar, low-sodium, vegetable-rich
      diets and makes them especially vulnerable to our current food environment of
      foods high in salt and refined sugars. The good news is that sensory experiences,
      beginning early in life, can shape preferences. Mothers who consume diets rich in
      healthy foods can get children off to a good start because flavors are
      transmitted from the maternal diet to amniotic fluid and mother's milk, and
      breastfed infants are more accepting of these flavors. In contrast, infants fed
      formula learn to prefer its unique flavor profile and may have more difficulty
      initially accepting flavors not found in formula, such as those of fruit and
      vegetables. Regardless of early feeding mode, infants can learn through repeated
      exposure and dietary variety if caregivers focus on the child's willingness to
      consume a food and not just the facial expressions made during feeding. In
      addition, providing complementary foods low in salt and sugars may help protect
      the developing child from excess intake later in life. Early-life experiences
      with healthy tastes and flavors may go a long way toward promoting healthy
      eating, which could have a significant impact in addressing the many chronic
      illnesses associated with poor food choice. 

PMID- 24452240
TI  - BMI and all-cause mortality in older adults: a meta-analysis.
AB  - BACKGROUND: Whether the association between body mass index (BMI) and all-cause
      mortality for older adults is the same as for younger adults is unclear.
      OBJECTIVE: The objective was to determine the association between BMI and all
      cause mortality risk in adults >=65 y of age. DESIGN: A 2-stage random-effects
      meta-analysis was performed of studies published from 1990 to 2013 that reported
      the RRs of all-cause mortality for community-based adults aged >=65 y. RESULTS:
      Thirty-two studies met the inclusion criteria; these studies included 197,940
      individuals with an average follow-up of 12 y. With the use of a BMI (in kg/m2)
      of 23.0-23.9 as the reference, there was a 12% greater risk of mortality for a
      BMI range of 21.0-21.9 and a 19% greater risk for a range of 20.0-20.9 [BMI of
      21.0-21.9; HR (95% CI): 1.12 (1.10, 1.13); BMI of 20.0-20.9; HR (95% CI): 1.19
      (1.17, 1.22)]. Mortality risk began to increase for BMI >33.0 [BMI of 33.0-33.9;
      HR (95% CI): 1.08 (1.00, 1.15)]. Self-reported anthropometric measurements,
      adjustment for intermediary factors, and exclusion of early deaths or preexisting
      disease did not markedly alter the associations, although there was a slight
      attenuation of the association in never-smokers. CONCLUSIONS: For older
      populations, being overweight was not found to be associated with an increased
      risk of mortality; however, there was an increased risk for those at the lower
      end of the recommended BMI range for adults. Because the risk of mortality
      increased in older people with a BMI <23.0, it would seem appropriate to monitor
      weight status in this group to address any modifiable causes of weight loss
      promptly with due consideration of individual comorbidities.

PMID- 24452239
TI  - The marriage of nutrigenomics with the microbiome: the case of infant-associated
      bifidobacteria and milk.
AB  - Broadly, nutrigenomics examines the association of exogenous nutrients and
      molecular responses to maintain homeostasis in an individual. Phenotypic
      expression profiling, often transcriptomics, has been applied to identify markers
      and metabolic consequences of suboptimal diet, lifestyle, or both. The decade
      after the Human Genome Project has been marked with advances in high-throughput
      analysis of biological polymers and metabolites, prompting a rapid increase in
      characterization of the profound nature by which our symbiotic microbiota
      influences human physiology. Although the technology is widely accessible to
      assess microbiome composition, genetic potential, and global function,
      nutrigenomics studies often exclude the microbial contribution to host responses
      to ingested nutritive molecules. Perhaps a hallmark of coevolution, milk provides
      a dramatic example of a diet that promotes a particular microbial community
      structure, because the lower infant gastrointestinal tract is often dominated by
      bifidobacteria that flourish on milk glycans. Systems-level approaches should
      continue to be applied to examine the microbial communities in the context of
      their host's dietary habits and metabolic status. In addition, studies of
      isolated microbiota species should be encouraged to inform clinical studies and
      interventions as well as community studies. Whereas nutrigenomics research is
      beginning to account for resident microbiota, the need remains to consistently
      consider our microscopic partners in the human holobiont. 

PMID- 24452242
TI  - The interplay between mechanics and stability of viral cages.
AB  - The stability and strength of viral nanoparticles are crucial to fulfill the
      functions required through the viral cycle as well as using capsids for
      biomedical and nanotechnological applications. The mechanical properties of viral
      shells obtained through Atomic Force Microscopy (AFM) and continuum elasticity
      theory, such as stiffness or Young's modulus, have been interpreted very often in
      terms of stability. However, viruses are normally subjected to chemical rather
      than to mechanical aggression. Thus, a correct interpretation of mechanics in
      terms of stability requires an adequate linkage between the ability of viral
      cages to support chemical and mechanical stresses. Here we study the mechanical
      fragility and chemical stability of bacteriophage T7 in two different maturation
      states: the early proheads and the final mature capsids. Using chemical stress
      experiments we show that proheads are less stable than final mature capsids.
      Still, both particles present similar anisotropic stiffness, indicating that a
      continuum elasticity description in terms of Young's modulus is not an adequate
      measure of viral stability. In combination with a computational coarse-grained
      model we demonstrate that mechanical anisotropy of T7 emerges out of the discrete
      nature of the proheads and empty capsids. Even though they present the same
      stiffness, proheads break earlier and have fractures ten times larger than mature
      capsids, in agreement with chemical stability, thus demonstrating that fragility
      rather than stiffness is a better indicator of viral cages' stability. 

PMID- 24452241
TI  - RPL39L is an example of a recently evolved ribosomal protein paralog that shows
      highly specific tissue expression patterns and is upregulated in ESCs and HCC
      tumors.
AB  - Ribosomal proteins (RPs) have been shown to be able to impart selectivity on the
      translating ribosome implicating them in gene expression control. Many ribosomal
      proteins are highly conserved and recently a number of ribosomal protein paralogs
      have been described in mammals. We examined the expression pattern of RPs in
      differentiating mouse Embryonic Stem Cells (ESCs), paying particular attention to
      the RP paralogs. We find the RP paralog Rpl39l is highly expressed in ESC and its
      expression strongly correlates with hepatocellular carcinoma tumor (HCC) samples
      with high tumor grading and alpha-fetoprotein level giving it diagnostic
      potential. We further screen the expression pattern of all RPs and their paralogs
      across 22 different tissues. We find that the more recently evolved RP paralogs
      show a much greater level of tissue-specific expression. We propose that these RP
      paralogs evolved more recently to provide a greater level of gene expression
      control to higher eukaryotes. 

PMID- 24452243
TI  - Analysis of genes causing hypertension and stroke in spontaneously hypertensive
      rats: gene expression profiles in the brain.
AB  - Spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) are frequently
      used as rat models not only of essential hypertension and stroke, but also of
      attention-deficit hyperactivity disorder (ADHD). Normotensive Wistar-Kyoto rats
      (WKY) are used as the control rats in these cases. An increasing number of
      studies has demonstrated the critical role of the central nervous system in the
      development and maintenance of hypertension. In a previous study, we analyzed the
      gene expression profiles in the adrenal glands of SHR. Thus, in this study, we
      analyzed gene expression profiles in the brains of SHR in order to identify the
      genes responsible for causing hypertension and stroke, as well as those involved
      in ADHD. Using genome-wide microarray technology, we examined the gene expression
      profiles in the brains of 3 rat strains (SHR, SHRSP and WKY) when the rats were 3
      and 6 weeks of age, a period in which the rats are considered to be in a pre
      hypertensive state. Gene expression profiles in the brain were compared between
      SHR and WKY, and between SHRSP and SHR. A total of 179 genes showing a >4- or <-4
      fold change in expression were isolated, and candidate genes were selected using
      two different web tools: the first tool was the Database for Annotation,
      Visualization and Integrated Discovery (DAVID), which was used to search for
      significantly enriched genes, and categorized them using Gene Ontology (GO)
      terms, and the second was the network explorer of Ingenuity Pathway Analysis
      (IPA), which was used to search for interaction networks among SHR- and SHRSP
      specific genes. The IPA of SHR-specific genes revealed that prostaglandin E
      receptor 4 (Ptger4) is one of the candidate genes responsible for causing
      hypertension in SHR, and that albumin (Alb) and chymase 1 (Cma1) are also
      responsible for causing hypertension in SHR in the presence of angiotensinogen
      (Agt). Similar analyses of SHRSP-specific genes revealed that the angiotensin II
      receptor-associated gene (Agtrap) interacts with the FBJ osteosarcoma oncogene
      (Fos), and with the angiotensin II receptor type-1b (Agtr1b). As Agtrap and
      Agtr1b not only participate in the 'uptake of norepinephrine' and 'blood
      pressure', but also in the 'behavior' of SHRSP at 6 weeks of age, our data
      demonstrate a close association between hypertension and ADHD.

PMID- 24452244
TI  - [Mason I fracture - a simple injury?].
AB  - BACKGROUND: Mason I fractures of the radial head are judged to be simple injuries
      that can generally be treated nonoperatively. According to the current literature
      mainly good and excellent results can be expected. We present a case series of
      patients presenting to us due to complications of Mason I fractures. PATIENTS AND
      METHODS: We reviewed all cases of patients that were treated because of
      complaints following Mason I radial head fractures. In all, 16 patients (10 men
      and 6 women) were identified. Mean age was 37 years (range 16-59 years). Mean
      time between trauma and surgery was 25 months (range 1-108 months). RESULTS: Ten
      patients developed painful osteoarthritis with elbow stiffness and loose bodies,
      4 patients suffered a posterolateral rotatory instability that had to be treated
      with ligament reconstruction, 1 patient presented with a combined medial and
      lateral instability, and 1 patient with a symptomatic hypertophic plica
      posterolateralis. Diagnotics and therapeutic concepts of these complications will
      be presented. CONCLUSION: In light of the complications, Mason I fractures must
      be reevaluated. They remain the domain of conservative treatment but close follow
      up is recommended to recognize possible complications early in order to prevent
      stiffness, chronic instabilities, and osteoarthritis.

PMID- 24452245
TI  - The European functional tree of bird life in the face of global change.
AB  - Despite the recognized joint impact of climate and land cover change on facets of
      biodiversity and their associated functions, risk assessments have primarily
      evaluated impacts on species ranges and richness. Here we quantify the
      sensitivity of the functional structure of European avian assemblages to changes
      in both regional climate and land cover. We combine species range forecasts with
      functional-trait information. We show that species sensitivity to environmental
      change is randomly distributed across the functional tree of the European
      avifauna and that functionally unique species are not disproportionately
      threatened by 2080. However, projected species range changes will modify the mean
      species richness and functional diversity of bird diets and feeding behaviours.
      This will unequally affect the spatial structure of functional diversity, leading
      to homogenization across Europe. Therefore, global changes may alter the
      functional structure of species assemblages in the future in ways that need to be
      accounted for in conservation planning. 

PMID- 24452250
TI  - Dual fluorescence of excited state intra-molecular proton transfer of HBFO:
      mechanistic understanding, substituent and solvent effects.
AB  - A combined approach of the multiconfigurational perturbation theory with the Rice
      Ramsperger-Kassel-Marcus methodology has been employed to calculate the minimum
      potential energy profiles and the rates of excited state intra-molecular proton
      transfer (ESIPT) for the WOLED material molecule of HBFO and its four meta- or
      para-substituted compounds in gas phase, acetonitrile and cyclohexane solvents.
      The kinetic control for these reactions is quantitatively determined and
      extensively studied on the basis of the accurate potential energy surfaces when
      the thermodynamic factor associated with the free energy change becomes
      negligible in the case of the existence of a significant barrier in the ESIPT
      process. These computational efforts contribute to a deep understanding of the
      ESIPT mechanism, dual emission characteristics, kinetic controlling factor,
      substituent and solvent effects for these material molecules. The white light
      emission is generated by the establishment of dynamic equilibrium between enol
      and keto forms in the charge transfer excited SCT((1)pipi*) state. The
      performance of white light emission is quantitatively demonstrated to be mainly
      sensitive to the molecular tailoring approach of the electronic properties of
      meta- or para- substituents by the modulation of the forward/backward ESIPT rate
      ratio. The quality of white light emission is slightly tunable through its
      surrounding solvent environment. These computational results will provide a
      useful strategy for the molecular design of OLED and WOLED materials. 

PMID- 24452251
TI  - Time trends of Italian former smokers 1980-2009 and 2010-2030 projections using a
      Bayesian age period cohort model.
AB  - This study aimed to describe past time trends of the prevalence of former smokers
      in Italy and to estimate prevalence projections using a Bayesian approach. An age
      period-cohort (APC) analysis has been carried out in order to investigate the
      effect of the age, period and birth cohort on the prevalence of former smokers
      during 1980-2009. A Bayesian APC model with an autoregressive structure for the
      age, period and cohort parameters has been used to estimate future trends.
      Results showed that awareness of harm from smoking occurred at younger ages with
      each advancing cohort, and that women were more likely to attempt to stop smoking
      during pregnancies and breastfeeding, whereas men attempted to quit only when
      smoking-related diseases became evident. Projections of future trend recorded a
      further increase in the number of former smokers in future decades, showing an
      estimate of the "end of smoking" around years 2060 and 2055 in men and women,
      respectively. The application of the APC analysis to study the prevalence of
      former smokers turned out to be a useful method for the evaluation of past
      smoking trends, reflecting the effects of tobacco control policies on time and
      generations, and to make projections of future trend. 

PMID- 24452253
TI  - Health in the new scenarios for climate change research.
AB  - The climate change research community is developing a toolkit for creating new
      scenarios to explore and evaluate the extensive uncertainties associated with
      future climate change and development pathways. Components of the toolkit include
      pathways for greenhouse gas emissions over this century and their associated
      magnitude and pattern of climate change; descriptions of a range of possible
      socioeconomic development pathways, including qualitative narratives and
      quantitative elements; and climate change policies to achieve specific levels of
      radiative forcing and levels of adaptive capacity. These components are combined
      within a matrix architecture to create a scenario. Five reference socioeconomic
      development pathways have been described along axes describing increasing
      socioeconomic and environmental challenges to adaptation and to mitigation. This
      paper extends these global pathways to describe their possible consequences for
      public health and health care, and considers the additional elements that could
      be added to increase the relevance of the new scenarios to address a wider range
      of policy relevant questions than previously possible. 

PMID- 24452252
TI  - Climate change and public health policy: translating the science.
AB  - Public health authorities are required to prepare for future threats and need
      predictions of the likely impact of climate change on public health risks. They
      may get overwhelmed by the volume of heterogeneous information in scientific
      articles and risk relying purely on the public opinion articles which focus
      mainly on global warming trends, and leave out many other relevant factors. In
      the current paper, we discuss various scientific approaches investigating climate
      change and its possible impact on public health and discuss their different roles
      and functions in unraveling the complexity of the subject. It is not our
      objective to review the available literature or to make predictions for certain
      diseases or countries, but rather to evaluate the applicability of scientific
      research articles on climate change to evidence-based public health decisions. In
      the context of mosquito borne diseases, we identify common pitfalls to watch out
      for when assessing scientific research on the impact of climate change on human
      health. We aim to provide guidance through the plethora of scientific papers and
      views on the impact of climate change on human health to those new to the
      subject, as well as to remind public health experts of its multifactorial and
      multidisciplinary character. 

PMID- 24452254
TI  - Noise producing toys and the efficacy of product standard criteria to protect
      health and education outcomes.
AB  - An evaluation of 28 commercially available toys imported into New Zealand
      revealed that 21% of these toys do not meet the acoustic criteria in the ISO
      standard, ISO 8124-1:2009 Safety of Toys, adopted by Australia and New Zealand as
      AS/NZS ISO 8124.1:2010. While overall the 2010 standard provided a greater level
      of protection than the earlier 2002 standard, there was one high risk toy
      category where the 2002 standard provided greater protection. A secondary set of
      toys from the personal collections of children known to display atypical methods
      of play with toys, such as those with autism spectrum disorders (ASD), was part
      of the evaluation. Only one of these toys cleanly passed the 2010 standard, with
      the remainder failing or showing a marginal-pass. As there is no tolerance level
      stated in the standards to account for interpretation of data and experimental
      error, a value of +2 dB was used. The findings of the study indicate that the
      current standard is inadequate in providing protection against excessive noise
      exposure. Amendments to the criteria have been recommended that apply to the
      recently adopted 2013 standard. These include the integration of the new
      approaches published in the recently amended European standard (EN 71) on safety
      of toys. 

PMID- 24452255
TI  - Toxic metal concentrations in cigarettes obtained from U.S. smokers in 2009:
      results from the International Tobacco Control (ITC) United States survey cohort.
AB  - Smoking-related diseases can be attributed to the inhalation of many different
      toxins, including heavy metals, which have a host of detrimental health effects.
      The current study reports the levels of arsenic (As), cadmium (Cd), chromium
      (Cr), nickel (Ni), and lead (Pb) in cigarettes obtained from adult smokers
      participating in the 2009 wave of the ITC United States Survey (N = 320). The
      mean As, Cd, Cr, Ni, and Pb levels were 0.17, 0.86, 2.35, 2.21, and 0.44 ug/g,
      respectively. There were some differences in metal concentrations of cigarette
      brands produced by different manufacturers, suggesting differences in the source
      of tobaccos used by different companies. For Ni, there were significant pairwise
      differences between Philip Morris U.S. (PMUSA) and R.J. Reynolds (RJR) brands
      (PMUSA higher; p < 0.001), PMUSA and other manufacturer (OM) brands (PMUSA
      higher; p < 0.001), and RJR and OM brands (RJR higher; p = 0.006). For Cr, RJR
      brands had higher levels than did OM brands (p = 0.02). Levels of As, Cd, and Pb
      did not differ significantly across manufacturer groups (p > 0.10). Because of
      the variety of toxic heavy metals in cigarette tobacco, and their numerous
      negative health effects, metal content in cigarette tobacco should be reduced.

PMID- 24452256
TI  - A mobile multi-agent information system for ubiquitous fetal monitoring.
AB  - Electronic fetal monitoring (EFM) systems integrate many previously separate
      clinical activities related to fetal monitoring. Promoting the use of ubiquitous
      fetal monitoring services with real time status assessments requires a robust
      information platform equipped with an automatic diagnosis engine. This paper
      presents the design and development of a mobile multi-agent platform-based open
      information systems (IMAIS) with an automated diagnosis engine to support
      intensive and distributed ubiquitous fetal monitoring. The automatic diagnosis
      engine that we developed is capable of analyzing data in both traditional paper
      based and digital formats. Issues related to interoperability, scalability, and
      openness in heterogeneous e-health environments are addressed through the
      adoption of a FIPA2000 standard compliant agent development platform-the Java
      Agent Development Environment (JADE). Integrating the IMAIS with light-weight,
      portable fetal monitor devices allows for continuous long-term monitoring without
      interfering with a patient's everyday activities and without restricting her
      mobility. The system architecture can be also applied to vast monitoring
      scenarios such as elder care and vital sign monitoring. 

PMID- 24452257
TI  - Residential racial composition and black-white obesity risks: differential
      effects of neighborhood social and built environment.
AB  - This study investigates the association between neighborhood racial composition
      and adult obesity risks by race and gender, and explores whether neighborhood
      social and built environment mediates the observed protective or detrimental
      effects of racial composition on obesity risks. Cross-sectional data from the
      2006 and 2008 Southeastern Pennsylvania Household Health Survey are merged with
      census-tract profiles from 2005-2009 American Community Survey and Geographic
      Information System-based built-environment data. The analytical sample includes
      12,730 whites and 4,290 blacks residing in 953 census tracts. Results from
      multilevel analysis suggest that black concentration is associated with higher
      obesity risks only for white women, and this association is mediated by lower
      neighborhood social cohesion and socioeconomic status (SES) in black-concentrated
      neighborhoods. After controlling for neighborhood SES, black concentration and
      street connectivity are associated with lower obesity risks for white men. No
      association between black concentration and obesity is found for blacks. The
      findings point to the intersections of race and gender in neighborhood effects on
      obesity risks, and highlight the importance of various aspects of neighborhood
      social and built environment and their complex roles in obesity prevention by
      socio-demographic groups. 

PMID- 24452260
TI  - Size-induced enhanced magnetoelectric effect and multiferroicity in chromium
      oxide nanoclusters.
AB  - The control of the magnetization of a material with an electric field would make
      the design and the integration of novel electronic devices possible. This
      explains the renewed interest in multiferroic materials. Progress in this field
      is currently hampered by the scarcity of the materials available and the
      smallness of the magnetoelectric effects. Here we present a proof-of-principle
      experiment showing that engineering large strains through nanoscale size
      reduction is an efficient route for increasing magnetoelectric coefficients by
      orders of magnitude. The archetype magnetoelectric material, Cr2O3, in the form
      of epitaxial clusters, exhibits an unprecedented 600% change in magnetization
      magnitude under 1 V. Furthermore, a multiferroic phase, with both magnetic and
      electric spontaneous polarizations, is found in the clusters, while absent in the
      bulk.

PMID- 24452258
TI  - Objective indicators of physical activity and sedentary time and associations
      with subjective well-being in adults aged 70 and over.
AB  - This study explored the associations of the volume and intensity of physical
      activity and the volume of sedentary time with subjective well-being in a diverse
      group of 228 older adults in the UK (111 female, mean age 78.2 years (SD 5.8)).
      Physical activity (PA) and sedentary behaviour were assessed by accelerometry
      deriving mean steps per day, mean moderate/vigorous PA minutes per hour (MVPA min
      . h(-1)) and minutes of sedentary time per hour (ST min . h(-1)). Lower limb
      function was assessed by the Short Physical Performance Battery. Subjective well
      being was assessed using the SF-12 health status scale, the Ageing Well Profile
      and the Satisfaction with Life Scale. Linear regressions were used to investigate
      associations between the independent variables which included physical activity
      (steps and MVPA), sedentary time, participant characteristics (gender, age, BMI,
      education, number of medical conditions), and lower limb function and dependent
      variables which included mental and physical well-being. Steps, MVPA and lower
      limb function were independently and moderately positively associated with
      perceived physical well-being but relationships with mental well-being variables
      were weak. No significant associations between sedentary behaviours and well
      being were observed. The association between objectively evaluated physical
      activity and function and subjective evaluations of physical well-being suggest
      that improving perceptions of physical health and function may provide an
      important target for physical activity programmes. This in turn may drive further
      activity participation.

PMID- 24452261
TI  - Pharmacogenetics at 50: genomic personalization comes of age.
AB  - The study of the genetics of drug responses has a long history but has provided
      only a few examples of gene variants that are relevant clinically. Here, we
      discuss the current state of the pharmacogenomics field with emphasis on the
      potential of data generated through drug development in order to shed new light
      on genetic variants predictive of therapeutic outcomes-and likewise the potential
      of pharmacogenomics to improve clinical trial design. We note some examples in
      which data from clinical trials have already provided clear pharmacogenomic
      insights and suggest ways in which genomic technology might be used successfully
      in drug development. 

PMID- 24452262
TI  - Gene therapy prolongs survival and restores function in murine and canine models
      of myotubular myopathy.
AB  - Loss-of-function mutations in the myotubularin gene (MTM1) cause X-linked
      myotubular myopathy (XLMTM), a fatal, congenital pediatric disease that affects
      the entire skeletal musculature. Systemic administration of a single dose of a
      recombinant serotype 8 adeno-associated virus (AAV8) vector expressing murine
      myotubularin to Mtm1-deficient knockout mice at the onset or at late stages of
      the disease resulted in robust improvement in motor activity and contractile
      force, corrected muscle pathology, and prolonged survival throughout a 6-month
      study. Similarly, single-dose intravascular delivery of a canine AAV8-MTM1 vector
      in XLMTM dogs markedly improved severe muscle weakness and respiratory
      impairment, and prolonged life span to more than 1 year in the absence of
      toxicity or a humoral or cell-mediated immune response. These results demonstrate
      the therapeutic efficacy of AAV-mediated gene therapy for myotubular myopathy in
      small- and large-animal models, and provide proof of concept for future clinical
      trials in XLMTM patients. 

PMID- 24452263
TI  - Identifying gut microbe-host phenotype relationships using combinatorial
      communities in gnotobiotic mice.
AB  - Identifying a scalable, unbiased method for discovering which members of the
      human gut microbiota influence specific physiologic, metabolic, and immunologic
      phenotypes remains a challenge. We describe a method in which a clonally arrayed
      collection of cultured, sequenced bacteria was generated from one of several
      human fecal microbiota samples found to transmit a particular phenotype to
      recipient germ-free mice. Ninety-four bacterial consortia of diverse size,
      randomly drawn from the culture collection, were introduced into germ-free
      animals. We identified an unanticipated range of bacterial strains that promoted
      accumulation of colonic regulatory T cells (T(regs)) and expansion of Nrp1(lo/-)
      peripheral T(regs), as well as strains that modulated mouse adiposity and cecal
      metabolite concentrations, using feature selection algorithms and follow-up
      monocolonizations. This combinatorial approach enables a systems-level
      understanding of microbial contributions to human biology.

PMID- 24452264
TI  - Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked
      infantile spasms syndrome.
AB  - Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate
      treatment. In patients, mutation of ARX, a transcription factor selectively
      expressed in neuronal precursors and adult inhibitory interneurons, impairs cell
      migration and causes a major inherited subtype of the disease X-linked infantile
      spasms syndrome. Using an animal model, the Arx((GCG)10+7) mouse, we determined
      that brief estradiol (E2) administration during early postnatal development
      prevented spasms in infancy and seizures in adult mutants. E2 was ineffective
      when delivered after puberty or 30 days after birth. Early E2 treatment altered
      mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and
      restored depleted interneuron populations without increasing GABAergic synaptic
      density. Postnatal E2 treatment may induce lasting transcriptional changes that
      lead to enduring disease modification and could potentially serve as a therapy
      for inherited interneuronopathies. 

PMID- 24452265
TI  - SPAG7 is a candidate gene for the periodic fever, aphthous stomatitis,
      pharyngitis and adenopathy (PFAPA) syndrome.
AB  - Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome
      is an auto-inflammatory disease for which a genetic basis has been postulated.
      Nevertheless, in contrast to the other periodic fever syndromes, no candidate
      genes have yet been identified. By cloning, following long insert size paired-end
      sequencing, of a de novo chromosomal translocation t(10;17)(q11.2;p13) in a
      patient with typical PFAPA syndrome lacking mutations in genes associated with
      other periodic fever syndromes we identified SPAG7 as a candidate gene for PFAPA.
      SPAG7 protein is expressed in tissues affected by PFAPA and has been functionally
      linked to antiviral and inflammatory responses. Haploinsufficiency of SPAG7 due
      to a microdeletion at the translocation breakpoint leading to loss of exons 2-7
      from one allele was associated with PFAPA in the index. Sequence analyses of
      SPAG7 in additional patients with PFAPA point to genetic heterogeneity or
      alternative mechanisms of SPAG7 deregulation, such as somatic or epigenetic
      changes. 

PMID- 24452266
TI  - Plasmodium genetic loci linked to host cytokine and chemokine responses.
AB  - Both host and parasite factors contribute to disease severity of malaria
      infection; however, the molecular mechanisms responsible for the disease and the
      host-parasite interactions involved remain largely unresolved. To investigate the
      effects of parasite factors on host immune responses and pathogenesis, we
      measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice
      infected with two Plasmodium yoelii strains having different virulence phenotypes
      and in progeny from a genetic cross of the two parasites. Quantitative trait loci
      (QTL) analysis linked levels of many CCs, particularly IL-1beta, IP-10, IFN
      gamma, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite
      chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome
      sequences spanning the mapped loci revealed various candidate genes. The loci on
      chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1beta, IL-5
      and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017)
      interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10
      in parasitemia control and host mortality. These results provide important
      information for a better understanding of malaria pathogenesis and can be used to
      examine the role of these factors in human malaria infection. 

PMID- 24452267
TI  - Diubiquitin (Ubd) is a susceptibility gene for virus-triggered autoimmune
      diabetes in rats.
AB  - Genetic studies of type 1 diabetes (T1D) have been advanced by comparative
      analysis of multiple susceptible and resistant rat strains with a permissive
      class II MHC haplotype, RT1(u). LEW.1WR1 (but not resistant LEW.1W or WF) rats
      are susceptible to T1D induced by a TLR3 agonist polyinosinic:polycytidylic acid
      followed by infection with parvovirus. We have mapped genetic loci for virus
      induced T1D susceptibility, identifying a major susceptibility locus (Iddm37)
      near the MHC. The Iddm37 homologs on mouse and human chromosomes are also
      diabetes linked. We report that a major effect gene within Iddm37 is diubiquitin
      (Ubd). Gene expression profiling of pancreatic lymph nodes in susceptible and
      resistant rats during disease induction showed differences in Ubd transcript
      abundance. The LEW.1WR1 Ubd promoter allele leads to higher inducible levels of
      UBD than that of LEW.1W or WF. Using zinc-finger nucleases , we deleted a segment
      of the LEW.1WR1 Ubd gene and eliminated its expression. UBD-deficient rats show
      substantially reduced diabetes after viral infection. Complementary studies show
      that there may be another diabetes gene in addition to Ubd in the Iddm37
      interval. These data prove that Ubd is a diabetes susceptibility gene, providing
      insight into the interplay of multiple genes and environmental factors in T1D
      susceptibility. 

PMID- 24452268
TI  - Placental leptin gene methylation and macrosomia during normal pregnancy.
AB  - The present study examined the placental leptin (LEP) DNA methylation and mRNA
      levels in macrosomic infants from normal pregnancies. In total, 49 neonates with
      macrosomia, i.e., high birth weights of >= 4,000 g, and 52 neonates with normal
      birth weights between 2,500 g and 4,000 g were recruited from The Second
      Affiliated Hospital of Wenzhou Medical University (Wenzhou, Zhejiang) in China.
      Placental LEP promoter methylation and LEP transcript levels were determined by
      Sequenom MassARRAY and quantitative PCR, respectively. LEP promoter methylation
      and mRNA levels were not significantly different between the individuals with
      macrosomia and the controls. However, stratification revealed that individual CpG
      dinucleotides were hypermethylated in macrosomia (P<0.05) in primiparous females
      and at 39 weeks of gestation (P<0.05). Variations in methylation did not affect
      placental LEP expression. It was concluded that the methylation of the placental
      LEP promoter was altered during a specific gestational period in macrosomia
      following a normal pregnancy and under certain conditions. However, placental LEP
      expression was not affected.

PMID- 24452270
TI  - Quaternary Ti-20Nb-10Zr-5Ta alloy during immersion in simulated physiological
      solutions: formation of layers, dissolution and biocompatibility.
AB  - Samples of the quaternary Ti-20Nb-10Zr-5Ta alloy were immersed in Hanks'
      simulated physiological solution and in minimum essential medium (MEM) for 25
      days. Samples of Ti metal served as controls. During immersion, the concentration
      of ions dissolved in MEM was measured by inductively coupled plasma mass
      spectrometry, while at the end of the experiment the composition of the surface
      layers was analyzed by X-ray photoelectron spectroscopy, and their morphology by
      scanning electron microscopy equipped for chemical analysis. The surface layer
      formed during immersion was comprised primarily of TiO2 but contained oxides of
      alloying elements as well. The degree of oxidation differed for different metal
      cations; while titanium achieved the highest valency, tantalum remained as the
      metal or is oxidized to its sub-oxides. Calcium phosphate was formed in both
      solutions, while formation of organic-related species was observed only in MEM.
      Dissolution of titanium ions was similar for metal and alloy. Among alloying
      elements, zirconium dissolved in the largest quantity. The long-term effects of
      alloy implanted in the recipient's body were investigated in MEM, using two types
      of human cells-an osteoblast-like cell line and immortalized pulmonary
      fibroblasts. The in vitro biocompatibility of the quaternary alloy was similar to
      that of titanium, since no detrimental effects on cell survival, induction of
      apoptosis, delay of growth, or change in alkaline phosphatase activity were
      observed on incubation in MEM.

PMID- 24452269
TI  - Long term exposure to ambient air pollution and incidence of acute coronary
      events: prospective cohort study and meta-analysis in 11 European cohorts from
      the ESCAPE Project.
AB  - OBJECTIVES: To study the effect of long term exposure to airborne pollutants on
      the incidence of acute coronary events in 11 cohorts participating in the
      European Study of Cohorts for Air Pollution Effects (ESCAPE). DESIGN: Prospective
      cohort studies and meta-analysis of the results. SETTING: Cohorts in Finland,
      Sweden, Denmark, Germany, and Italy. PARTICIPANTS: 100 166 people were enrolled
      from 1997 to 2007 and followed for an average of 11.5 years. Participants were
      free from previous coronary events at baseline. MAIN OUTCOME MEASURES: Modelled
      concentrations of particulate matter <2.5 MUm (PM2.5), 2.5-10 MUm (PMcoarse), and
      <10 MUm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides,
      and traffic exposure at the home address based on measurements of air pollution
      conducted in 2008-12. Cohort specific hazard ratios for incidence of acute
      coronary events (myocardial infarction and unstable angina) per fixed increments
      of the pollutants with adjustment for sociodemographic and lifestyle risk
      factors, and pooled random effects meta-analytic hazard ratios. RESULTS: 5157
      participants experienced incident events. A 5 MUg/m(3) increase in estimated
      annual mean PM2.5 was associated with a 13% increased risk of coronary events
      (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 MUg/m(3)
      increase in estimated annual mean PM10 was associated with a 12% increased risk
      of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between
      cohorts. Positive associations were detected below the current annual European
      limit value of 25 MUg/m(3) for PM2.5 (1.18, 1.01 to 1.39, for 5 MUg/m(3) increase
      in PM2.5) and below 40 MUg/m(3) for PM10 (1.12, 1.00 to 1.27, for 10 MUg/m(3)
      increase in PM10). Positive but non-significant associations were found with
      other pollutants. CONCLUSIONS: Long term exposure to particulate matter is
      associated with incidence of coronary events, and this association persists at
      levels of exposure below the current European limit values.

PMID- 24452271
TI  - A multilayer tissue engineered meniscus substitute.
AB  - Various methods have been tried to treat the main meniscus problem, meniscal
      tears, for which we believe tissue engineering could be a viable solution. In
      this study, a three dimensional, collagen-based meniscus substitute was prepared
      by tissue engineering using human fibrochondrocytes and a collagen based
      scaffold. This construct was made with 3 different collagen-based foams
      interspaced with two electrospun nano/microfibrous mats. The top layer was made
      of collagen type I-chondroitin sulfate-hyaluronic acid (Coll-CS-HA), and the
      middle and the bottom layers were made of only collagen type I with different
      porosities and thus with different mechanical properties. The mats of aligned
      fibers were a blend of collagen type I and poly(L-lactic acid-co-glycolic acid)
      (PLGA). After seeding with human fibrochondrocytes, cell attachment,
      proliferation, and production of extracellular matrix and glucoseaminoglycan were
      studied. Cell seeding had a positive effect on the compressive properties of
      foams and the 3D construct. The 3D construct with all its 5 layers had better
      mechanical properties than the individual foams. 

PMID- 24452272
TI  - Comparison of morphology and biocompatibility of acellular nerve scaffolds
      processed by different chemical methods.
AB  - To investigate the morphological differences among acellular rat nerve scaffolds
      processed by different chemical methods and compare the biocompatibility between
      rat nerve grafts processed by different chemical methods and rat adipose-derived
      stem cells in vitro. Acellular rat sciatic nerve scaffolds processed by two
      different chemical methods (the Sondell method and the optimized method) and
      normal rat sciatic nerves were used as control. The structure and components of
      nerve scaffold were observed under microscopy, the degrees of decellularization
      and demyelination of nerve scaffold and integrity of nerve fiber tubes were
      assessed. The rat adipose-derived stem cells growth and adherence on scaffold
      were studied by scanning electron microscopy, the activity and adhesive ratio of
      rat adipose-derived stem cells in the nerve scaffold were compared. The basal
      lamina tubes and the extracellular matrix in the epineurium and perineurium in
      the nerve graft of optimized method were better preserved than the nerve graft of
      the Sondell method. After co-cultured with scaffolds, the difference of cell
      activity between three groups (two cell-scaffold combinations and control group)
      at the same observation time were not statistically significant (P > 0.05),the
      adhesive ratio of rat adipose-derived stem cells in the scaffold of the optimized
      method was better than that of the Sondell method. The scaffold of the optimized
      method is more effective than the scaffold of the Sondell method for peripheral
      nerve tissue engineering.

PMID- 24452273
TI  - Surface-immobilized DNAzyme-type biocatalysis.
AB  - The structure of the double helix of deoxyribonucleic acid (DNA, also called
      duplex-DNA) was elucidated sixty years ago by Watson, Crick, Wilkins and
      Franklin. Since then, DNA has continued to hold a fascination for researchers in
      diverse fields including medicine and nanobiotechnology. Nature has indeed
      excelled in diversifying the use of DNA: beyond its canonical role of repository
      of genetic information, DNA could also act as a nanofactory able to perform some
      complex catalytic tasks in an enzyme-mimicking manner. The catalytic capability
      of DNA was termed DNAzyme; in this context, a peculiar DNA structure, a quadruple
      helix also named quadruplex-DNA, has recently garnered considerable interest
      since its autonomous catalytic proficiency relies on its higher-order folding
      that makes it suitable to interact efficiently with hemin, a natural cofactor of
      many enzymes. Quadruplexes have thus been widely studied for their hemoprotein
      like properties, chiefly peroxidase-like activity, i.e., their ability to perform
      hemin-mediated catalytic oxidation reactions. Recent literature is replete with
      applications of quadruplex-based peroxidase-mimicking DNAzyme systems. Herein, we
      take a further leap along the road to biochemical applications, assessing the
      actual efficiency of catalytic quadruplexes for the detection of picomolar levels
      of surface-bound analytes in an enzyme-linked immunosorbent (ELISA)-type assay.
      To this end, we exploit an innovative strategy based on the functionalization of
      DNA by a multitasking platform named RAFT (for regioselectivity addressable
      functionalized template), whose versatility enables the grafting of DNA whatever
      its nature (duplex-DNA, quadruplex-DNA, etc.). We demonstrate that the resulting
      biotinylated RAFT/quadruplex systems indeed acquire catalytic properties that
      allow for efficient luminescent detection of picomoles of surface-bound
      streptavidin. We also highlight some of the pitfalls that have to be faced during
      optimization, notably demonstrating that highly optimized experimental conditions
      can make DNA pre-catalysts catalytically competent whatever their secondary
      structures. 

PMID- 24452275
TI  - Effect of chromophore encapsulation on linear and nonlinear optical properties:
      the case of "miniSOG", a protein-encased flavin.
AB  - Linear and nonlinear spectroscopic parameters of flavin mononucleotide, FMN, have
      been examined both experimentally and computationally under conditions in which
      FMN is (1) solvated in a buffered aqueous solution, and (2) encased in a protein
      that is likewise solvated in a buffered aqueous solution. The latter was achieved
      using "miniSOG" which is an FMN-containing protein engineered from Arabidopsis
      thaliana phototropin 2. Although it is reasonable to expect that the encasing
      protein could have an appreciable effect, certainly on the nonlinear two-photon
      absorption cross section, we find that replacing the dynamic aqueous environment
      with the more static protein environment does little to influence the
      spectroscopic properties of FMN. The experimental and computational studies are
      consistent in this regard, and this agreement indicates that comparatively high
      level computational methods can indeed be used with success on large chromophores
      with a complicated local environment. The results of the present study facilitate
      the much-needed development of well-characterized and readily-controlled
      chromophores suitable for use as intracellular sensitizers and fluorophores. 

PMID- 24452276
TI  - 4th International Symposium on Metallomics, 2013.

PMID- 24452274
TI  - Cystatin B is a progression marker of human epithelial ovarian tumors mediated by
      the TGF-beta signaling pathway.
AB  - Advanced ovarian cancer is a devastating disease. Gaining biomarkers of early
      detection during ovarian tumorigenesis may lead to earlier diagnosis and better
      therapeutic strategies. Cystatin B (CSTB) functions as an inhibitor to suppress
      intracellular cysteine proteases and has been implicated in several types of
      cancers. The present study explored the expression of CSTB in human ovarian
      tumors, to investigate CSTB expression associated with clinicopathological
      features, and to examine the effect of transforming growth factor-beta (TGF
      beta), which plays a key role in ovarian tumorigenesis, on CSTB expression in
      ovarian cancer cells. The ovarian tissue samples from 33 patients were retrieved.
      The expression of CSTB in ovarian tissue was examined by immunohistochemistry. We
      found that CSTB was over-expressed in human ovarian surface epithelial tumors,
      including serous, mucinous and clear cell tumors. The immunoreactive staining of
      CSTB was strong in borderline and malignant tumors, weak in benign tumors, and
      negative in normal tissue counterparts, but was not correlated with the
      clinicopathological features of patients with ovarian tumors, such as age,
      histological types, tumor size, lymph node metastasis and clinical stages. The
      CSTB at mRNA and protein levels in two types of epithelial ovarian cancer cells,
      OVCAR-3 and SK-OV-3, was decreased after TGF-beta1 treatment detected by
      quantitative PCR and western blot analysis, respectively. The inhibitory effect
      of TGF-beta1 on CSTB expression was abolished in the presence of SB-431542, a TGF
      beta type I receptor kinase inhibitor. Our data suggest that CSTB is tumor tissue
      specific and overexpressed in ovarian borderline and malignant tumors. The
      increased CSTB expression in ovarian tissue represents tumor progression and is
      dysregulated by the TGF-beta signaling pathway. CSTB may become a novel
      diagnostic intracellular biomarker for the early detection of ovarian cancer.

PMID- 24452277
TI  - Efficient immunization strategies to prevent financial contagion.
AB  - Many immunization strategies have been proposed to prevent infectious viruses
      from spreading through a network. In this work, we study efficient immunization
      strategies to prevent a default contagion that might occur in a financial
      network. An essential difference from the previous studies on immunization
      strategy is that we take into account the possibility of serious side effects.
      Uniform immunization refers to a situation in which banks are "vaccinated" with a
      common low-risk asset. The riskiness of immunized banks will decrease
      significantly, but the level of systemic risk may increase due to the de
      diversification effect. To overcome this side effect, we propose another
      immunization strategy, called counteractive immunization, which prevents pairs of
      banks from failing simultaneously. We find that counteractive immunization can
      efficiently reduce systemic risk without altering the riskiness of individual
      banks. 

PMID- 24452278
TI  - Synchronization of spin Hall nano-oscillators to external microwave signals.
AB  - Recently, a novel type of spin-torque nano-oscillators driven by pure spin
      current generated via the spin Hall effect was demonstrated. Here we report the
      study of the effects of external microwave signals on these oscillators. Our
      results show that they can be efficiently synchronized by applying a microwave
      signal at approximately twice the frequency of the auto-oscillation, which opens
      additional possibilities for the development of novel spintronic devices. We find
      that the synchronization exhibits a threshold determined by magnetic fluctuations
      pumped above their thermal level by the spin current, and is significantly
      influenced by the nonlinear self-localized nature of the auto-oscillatory mode. 

PMID- 24452279
TI  - Molecular mechanisms and treatment targets of muscle wasting and cachexia in
      heart failure: an overview.
AB  - PURPOSE OF REVIEW: This article aims to describe molecular pathways involved in
      the development of muscle wasting and cachexia, diagnostic possibilities, and
      potential treatments that have seen clinical testing in recent heart failure
      trials. An understanding of the specific changes that cause an anabolic-catabolic
      imbalance is an essential first step in the development of pharmaceutical
      intervention strategies aimed at blocking muscle wasting. RECENT FINDINGS:
      Skeletal muscle mass and muscle strength are the most important determinants of
      exercise capacity in patients with heart failure. In contrast to cachexia, muscle
      wasting is not usually associated with weight loss, implying the need for
      sophisticated assessment methods to correctly diagnose muscle wasting, for
      example the use of computed tomography, magnetic resonance imaging, or dual
      energy X-ray absorptiometry. Simpler techniques such as handgrip strength,
      exercise testing, or even a biomarker may help in determining patients with a
      high pre-test probability of muscle wasting. SUMMARY: Despite intensive research
      efforts in the field of muscle wasting during the last couple of decades, no
      effective treatment of muscle wasting currently exists other than exercise
      training. This situation remains true even though study of the molecular pathways
      involved in muscle wasting suggests many therapeutic targets. Easily applicable
      diagnostic tools may help to identify patients at risk of developing muscle
      wasting.

PMID- 24452280
TI  - Clinical remission of primary aggressive CD8+ cutaneous T-cell lymphoma after
      pralatrexate infusion.

PMID- 24452281
TI  - Scaling calibration in region of interest reconstruction with the 1D and 2D
      ATRACT algorithm.
AB  - PURPOSE: Recently, a reconstruction algorithm for region of interest (ROI)
      imaging in C-arm CT was published, named Approximate Truncation Robust Algorithm
      for Computed Tomography (ATRACT). Even in the presence of substantial data
      truncation, the algorithm is able to reconstruct images without the use of
      explicit extrapolation or prior knowledge. However, the method suffers from a
      scaling and offset artifact in the reconstruction. Hence, the reconstruction
      results are not quantitative. It is our goal to reduce the scaling and offset
      artifact so that Hounsfield unit (HU) values can be used for diagnosis. METHODS:
      In this paper, we investigate two variants of the ATRACT method and present the
      analytical derivations of these algorithms in the Fourier domain. Then, we
      propose an empirical correction measure that can be applied to the ATRACT
      algorithm, to effectively compensate the scaling and offset issue. The proposed
      method is evaluated on ten clinical datasets in the presence of different degrees
      of artificial truncation. RESULTS: With the proposed correction approach, we
      achieved an average relative root-mean-square error (rRMSE) of 2.81% with respect
      to non-truncated Feldkamp, Davis, and Kress reconstruction, even for severely
      truncated data. The rRMSE is reduced to as little as 10% of the image
      reconstructed without the scaling calibration. CONCLUSIONS: The reconstruction
      results show that ROI reconstruction of high accuracy can be achieved since the
      scaling and offset artifact are effectively eliminated by the proposed method.
      With this improvement, the HU values may be used for post-processing operations
      such as bone or soft tissue segmentation if some tolerance is accepted.

PMID- 24452283
TI  - Dose adjustment of carboplatin in patients on hemodialysis.
AB  - Carboplatin is one of the most prescribed cytotoxic drug, which is extensively
      used in the treatment regimens of several malignancies. The therapeutic
      efficiency of carboplatin has been found to correlate the area under curve (AUC).
      The Calvert formula has been extensively used to determine the dose of
      carboplatin for a fixed AUC and glomerular filtration rate (GFR). This formula
      has also been used in patients with end-stage renal disease on hemodialysis by
      assuming that the GFR is zero. This is applicable to patients who receive
      hemodialysis within 12-18 h after carboplatin infusion. After the first 24 h, a
      majority of the carboplatin is bound to proteins is not easily dialyzable and
      hence continues to remain in the blood stream despite repeated sessions of
      hemodialysis. We derive a correction factor to calculate the resultant AUC in
      such patients. The analysis done by using this correction factor shows that the
      AUC can increase by eightfold in patients who received the adjusted dose but
      whose hemodialysis was delayed beyond 24 h after infusion. The correction factor
      proposed here can also be used to calculate the dose adjustment required a priori
      in patients who may receive delayed hemodialysis. It is also useful to predict
      the AUC and estimate the resultant toxicity in such patients. 

PMID- 24452284
TI  - Dinuclear Mn(II,II) complexes: magnetic properties and microwave assisted
      oxidation of alcohols.
AB  - A series of six new mixed-ligand dinuclear Mn(II,II) complexes of three different
      hydrazone Schiff bases (H3L(1), H3L(2) and H3L(3)), derived from condensation of
      the aromatic acid hydrazides benzohydrazide, 2-aminobenzohydrazide or 2
      hydroxybenzohydrazide, with 2,3-dihydroxy benzaldehyde, respectively, is
      reported. Reactions of Mn(NO3)2.4H2O with the H3L(1-3) compounds, in the presence
      of pyridine (1 : 1 : 1 mole ratio), in methanol at room temperature, yield
      [Mn(H2L(1))(py)(H2O)]2(NO3)2.2H2O (1.2H2O), [Mn(H2L(2))(py)(CH3OH)]2(NO3)2.4H2O
      (2.4H2O) and [Mn(H2L(3))(py)(H2O)]2(NO3)2 (3) respectively, whereas the use of
      excess pyridine yields complexes with two axially coordinated pyridine molecules
      at each Mn(II) centre, viz. [Mn(H2L(1))(py)2]2(NO3)2.H2O (4.H2O),
      [Mn(H2L(2))(py)2]2(NO3)2.2H2O (5.2H2O) and [Mn(H2L(3))(py)2]2(NO3)2.2CH3OH
      (6.2CH3OH), respectively. In all the complexes, the (H2L(1-3))(-) ligand
      coordinates in the keto form. Complexes 1.2H2O, 2.4H2O, 4.H2O, 5.2H2O and
      6.2CH3OH are characterized by single crystal X-ray diffraction analysis. The
      complexes 1, 2 and 6, having different coordination environments, have been
      selected for variable temperature magnetic susceptibility measurements to examine
      the nature of magnetic interaction between magnetically coupled Mn(II) centres
      and also for exploration of the catalytic activity towards microwave assisted
      oxidation of alcohols. A yield of 81% (acetophenone) is obtained using a maximum
      of 0.4% molar ratio of catalyst relative to the substrate in the presence of
      TEMPO and in aqueous basic solution, under mild conditions.

PMID- 24452282
TI  - Association between epidermal growth factor receptor gene copy number and ERCC1,
      BRCA1 protein expression in Chinese patients with non-small cell lung cancer.
AB  - Mutation in epidermal growth factor receptor (EGFR) gene may predict response to
      chemotherapy in non-small cell lung cancer (NSCLC). However, the correlation
      between EGFR gene copy status and protein levels of drug-resistant genes, such as
      excision repair cross-complementing 1 (ERCC1) and breast cancer 1 (BRCA1),
      remains unclear. We retrospectively analyzed formalin-fixed, paraffin-embedded
      tumor tissues from 109 Chinese patients with NSCLC. EGFR gene copy number was
      evaluated by fluorescence in situ hybridization (FISH), and protein levels of
      platinum-resistance-associated genes, including ERCC1 and BRCA1, were determined
      by immunohistochemical staining. High EGFR gene copy (EGFR FISH-positive) was
      found in 21.1% of the patients (amplification in 7.3% and high polysomy in 13.8%,
      respectively). Immunohistochemical analysis revealed that ERCC1 protein
      expression was not associated with clinicopathological factors, whereas a
      significantly higher BRCA1 positive rate was found in poorly differentiated
      tumors (P=0.02). Further association studies demonstrated that EGFR gene copy
      number status was not correlated with protein levels of ERCC1 or BRCA1; however,
      expression of ERCC1 was significantly associated with that of BRCA1 in this set
      of Chinese patients with NSCLC (P<0.001, r=0.484). Our study demonstrated that
      EGFR gene copy number status was not correlated with ERCC1 or BRCA1 protein
      expression, but ERCC1 protein levels were significantly correlated to BRCA1
      protein expression levels in tumor tissues from Chinese patients with NSCLC.

PMID- 24452285
TI  - A new marine reptile from the Triassic of China, with a highly specialized
      feeding adaptation.
AB  - The Luoping fauna (Anisian, Middle Triassic) is probably the oldest of Triassic
      faunas in Guizhou-Yunnan area, China. The reptilian assemblage is comprised of
      ichthyosaurs, a number of sauropterygians (pachypleurosaur-like forms),
      saurosphargids, protorosaurs, and archosauriforms. Here, we report on a peculiar
      reptile, newly found in this fauna. Its dentition is fence or comb-like and bears
      more than 175 pleurodont teeth in each ramus of the upper and lower jaws, tooth
      crown is needle-like distally and blade-shaped proximally; its rostrum strongly
      bends downward and the anterior end of its mandible expands both dorsally and
      ventrally to form a shovel-headed structure; and its ungual phalanges are hoof
      shaped. The specializations of the jaws and dentition indicate that the reptile
      may have been adapted to a way of bottom-filter feeding in water. It is obvious
      that such delicate teeth are not strong enough to catch prey, but were probably
      used as a barrier to filter microorganisms or benthic invertebrates such as sea
      worms. These were collected by the specialized jaws, which may have functioned as
      a shovel or pushdozer (the mandible) and a grasper or scratcher (the rostrum).
      Our preliminary analysis suggests that the new reptile might be more closely
      related to the Sauropterygia than to other marine reptiles.

PMID- 24452286
TI  - A novel CO2-stable dual phase membrane with high oxygen permeability.
AB  - By cobalt-doping of the mixed conducting phase PSFC, a good combination of high
      CO2 stability and high oxygen permeability is obtained for the 60 wt%
      Ce(0.9)Pr(0.1)O(2-delta)-40 wt% Pr(0.6)Sr(0.4)Fe(0.5)Co(0.5)O(3-delta) (CP-PSFC)
      dual phase membrane, which suggests that CP-PSFC is a promising membrane for
      industrial applications in the oxyfuel process for CO2 capture.

PMID- 24452287
TI  - Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and
      Hrb1.
AB  - Eukaryotic cells have to prevent the export of unspliced pre-mRNAs until intron
      removal is completed to avoid the expression of aberrant and potentially harmful
      proteins. Only mature mRNAs associate with the export receptor Mex67/TAP and
      enter the cytoplasm. Here we show that the two shuttling serine/arginine (SR)
      proteins Gbp2 and Hrb1 are key surveillance factors for the selective export of
      spliced mRNAs in yeast. Their absence leads to the significant leakage of
      unspliced pre-mRNAs into the cytoplasm. They bind to pre-mRNAs and the
      spliceosome during splicing, where they are necessary for the surveillance of
      splicing and the stable binding of the TRAMP complex to spliceosome-bound
      transcripts. Faulty transcripts are marked for their degradation at the nuclear
      exosome. On correct mRNAs the SR proteins recruit Mex67 upon completion of
      splicing to allow a quality controlled nuclear export. Altogether, these data
      identify a role for shuttling SR proteins in mRNA surveillance and nuclear mRNA
      quality control. 

PMID- 24452288
TI  - In silico search for multi-target therapies for osteoarthritis based on 10 common
      Huoxue Huayu herbs and potential applications to other diseases.
AB  - Huoxue Huayu (HXHY) has been widely used in traditional Chinese medicine (TCM) as
      a key therapeutic principle for osteoarthritis (OA), and related herbs have been
      widely prescribed to treat OA in the clinic. The aims of the present study were
      to explore a multi-target therapy for OA using 10 common HXHY herbs and to
      investigate their potential applications for treatment of other diseases. A novel
      computational simulation approach that integrates chemical structure, ligand
      clusters, chemical space and drug-likeness evaluations, as well as docking and
      network analysis, was used to investigate the properties and effects of the
      herbs. The compounds contained in the studied HXHY herbs were divided into 10
      clusters. Comparison of the chemical properties of these compounds to those of
      other compounds described in the DrugBank database indicated that the properties
      of the former are more diverse than those of the latter and that most of the HXHY
      derived compounds do not violate the 'Lipinski's rule of five'. Docking analysis
      allowed for the identification of 39 potential bioactive compounds from HXHY
      herbs and 11 potential targets for these compounds. The identified targets were
      closely associated with 49 diseases, including neoplasms, musculoskeletal,
      nervous system and cardiovascular diseases. Ligand-target (L-T) and ligand-target
      disease (L-T-D) networks were constructed in order to further elucidate the
      pharmacological effects of the herbs. Our findings suggest that a number of
      compounds from HXHY herbs are promising candidates for mult-target therapeutic
      application in OA and may exert diverse pharmacological effects, affecting
      additional diseases besides OA.

PMID- 24452289
TI  - Oral ketamine augmentation for chronic suicidality in treatment-resistant
      depression.

PMID- 24452290
TI  - Location, size, and distance: criteria for quality in esophagogastroduodenos copy
      reporting for pre-operative gastric cancer evaluation.
AB  - BACKGROUND: There is a lack of existing literature regarding the quality of
      esophagogastroduodenoscopy (EGD) reporting for gastric cancer evaluation. This
      study aims to determine criteria for quality endoscopic evaluation of gastric
      cancer in North America by identifying important features of the EGD report for
      pre-operative evaluation of gastric cancer and assessing inclusion of these
      features in existing reports. METHODS: Semi-structured interviews were conducted
      with experienced endoscopists from community and academic hospitals affiliated
      with the University of Toronto to identify essential elements for an EGD report.
      Then, 225 EGD reports from 2005 to 2008 were evaluated by two trained reviewers
      for inclusion of recommended EGD report elements and global assessment of report
      quality and adequacy for surgical planning. RESULTS: Essential elements
      recommended by interviewed endoscopists include tumor size, location, and
      distance from gastroesophageal junction (GEJ). Approximately 95 % of all reports
      documented the location of lesions, <5 % documented distance from the GEJ, and
      <15 % documented tumor size. Overall report quality was rated as excellent for 4
      5 % of reports; 20-42 % of all reports were deemed to be adequate for surgical
      planning. All surgeons interviewed as part of the endoscopist panel indicated
      that they would repeat the EGD before consulting with patients regarding surgical
      planning. CONCLUSIONS: For pre-operative evaluation of gastric cancer, tumor
      size, location, and distance from key anatomical landmarks were proposed as
      essential elements of a quality EGD report. Most of the reviewed reports did not
      document these elements. Report quality is perceived to be poor and may lead to
      repeat endoscopy. Developing a standardized EGD reporting format based on
      inclusion of individual parameters can improve the quality of gastric cancer
      management.

PMID- 24452291
TI  - Thyroid surgery without antibiotic prophylaxis: experiences with 1,030 patients
      from a teaching hospital in China.
AB  - OBJECTIVE: Our objective was to evaluate the outcome of thyroidectomy without the
      use of prophylactic antibiotics. This study was held from January 2005 to May
      2012 in a teaching hospital in Dongguan, China. METHODS: A total of 1,030
      thyroidectomy patients were retrospectively reviewed and basic data were
      recorded, including age, sex, peri-operative antibiotic use, type of thyroid
      surgery done, and post-operative complications. Either an open approach or an
      endoscopic approach was performed according to the doctor's or patient's
      preference following a strict aseptic technique. The drain was routinely placed.
      Any complications were analyzed. RESULTS: A total of 834 (81 %) females and 196
      (19 %) males were included, giving a ratio of 4.2:1. The average age was 38.3
      years. The mean operation time was 85.3 min. Pathological type included 818 (79.4
      %) nodular goiter, 34 (3.3 %) Graves' disease, 102 (9.9 %) nodular papillary
      hyperplasia, 12 (1.2 %) Hashimoto's disease, 62 (6 %) papillary carcinoma, and 2
      (0.2 %) medullary carcinoma. Four patients had postoperative bleeding, four had
      temporally recurrent nerve paralysis. Only one had wound infection (0.09 %).
      CONCLUSION: Antibiotic prophylaxis in elective thyroidectomy is not an essential
      pre-operation preparation for all patients, if guidelines for antibiotic
      prophylaxis in clean surgery are adhered to and surgeons have sophisticated
      skills in the procedure.

PMID- 24452293
TI  - Chemoselective and repetitive intermolecular cross-acyloin condensation reactions
      between a variety of aromatic and aliphatic aldehydes using a robust N
      heterocyclic carbene catalyst.
AB  - We found that chemoselectivity of the crossed acyloin product is controlled by
      the adjustment of the aromatic aldehyde/aliphatic aldehyde ratio. Moreover, we
      observed the persistent catalytic activity of the homogeneous NHC catalyst in a
      solution due to NHC catalyst robustness. 

PMID- 24452292
TI  - Adrenal metastectomy is safe in selected patients.
AB  - BACKGROUND: The benefit of adrenalectomy (ADX) for adrenal metastasis is not
      established. We evaluated outcomes after ADX for patients with adrenal
      metastasis. METHODS: We retrospectively analyzed the records of 90 patients who
      underwent ADX for metastatic disease. Overall survival (OS) after ADX was
      calculated using the Kaplan-Meier method. Clinical factors were evaluated for
      associations with OS using a Cox regression model, and with operative factors
      using the Wilcoxon two-sample or Fisher's exact test. RESULTS: The most common
      primary tumor types were melanoma (35, 39 %) and lung cancer (32, 35 %). A total
      of 49 (54 %) patients had isolated adrenal metastasis; 55 (61 %) underwent
      laparoscopic resection (LADX). Median OS was 2.46 years (range < 1 month-15
      years), and 5-year survival rate was 38 % (6 % standard error). Most patients
      experienced disease progression (56, 62 %) despite achieving disease-free status
      following ADX (78, 86 %). When compared with the open approach, LADX was
      associated with smaller tumor size, as well as reduced blood loss, operative
      time, and length of stay (all p < 0.0001), and no difference in OS (p = 0.4122)
      or complications (p = 1). Isolated adrenal bed recurrence was similar in LADX (N
      = 3, 5 %) and open ADX (N = 2, 6 %) (p = 1), and did not affect OS (p = 0.2).
      Larger tumors were associated with shorter median OS (p = 0.0014). CONCLUSIONS:
      ADX for metastasis can be safely performed in selected patients. Some patients
      with adrenal metastasis achieve prolonged survival following ADX. Compared with
      an open approach, LADX has no measurable oncologic disadvantage, minimizes
      morbidity, and should be considered when tumor characteristics permit.

PMID- 24452294
TI  - Risk factors for anal fistula: a case-control study.
AB  - BACKGROUND: The aim of our study was to identify potential risk factors for anal
      fistula in order to improve prevention and treatment of anal fistula. METHODS: A
      retrospective case-control study for anal fistula was conducted at our unit.
      Logistic regression analyses were carried out to identify associated risk factors
      for anal fistula. RESULTS: The final model obtained by the stepwise forward
      logistic regression analysis method identified the following items as independent
      risk factors: body mass index of >25.0 kg/m(2), high daily salt intake, history
      of diabetes, hyperlipidemia, dermatosis, anorectal surgery, history of smoking
      and alcohol intake, sedentary lifestyle, excessive intake of spicy/greasy food,
      very infrequent participation in sports and prolonged sitting on the toilet for
      defecation. CONCLUSIONS: Our results indicate that lifestyle factors and certain
      medical conditions increase an individual's risk of developing anal fistula.

PMID- 24452295
TI  - Screening of differentially expressed genes related to esophageal squamous cell
      carcinoma and functional analysis with DNA microarrays.
AB  - The aim of this study was to find disease-associated genes and gene functions in
      esophageal squamous cell carcinoma (ESCC) with DNA microarrays. We downloaded the
      gene expression profile GSE20347 from the Gene Expression Omnibus database
      including 17 ESCC and 17 matched normal adjacent tissue samples. Compared with
      normal samples, the probe level data were pre-processed and the differentially
      expressed genes (DEGs) were identified (FDR <0.05, and |logFC|>2) with packages
      in R language. The selected DEGs were further analyzed with bioinformatic
      methods. After an interaction network of DEGs was constructed by STRING, we
      selected the most important hub gene through network topological analysis
      (including node degree, clustering coefficient and path length) and analyzed
      functions and pathways of the hub gene network. A total of 538 genes were
      filtered as DEGs between normal and disease samples, and we selected the gene
      TSPO as the most important hub gene. Among its interactors, the CTSK gene and the
      IL8 gene participated in the toll-like receptor signaling pathway which is
      closely related to tumor occurrence. The TSPO gene and its interactors may affect
      the cancer-specific gene expression by participating in the toll-like receptor
      signaling pathway. Our discovery may be useful in investigating the complex
      interacting mechanisms underlying the disease. However, further experiments are
      still needed to confirm our result. 

PMID- 24452296
TI  - Surface induced dissociation yields quaternary substructure of refractory
      noncovalent phosphorylase B and glutamate dehydrogenase complexes.
AB  - Ion mobility (IM) and tandem mass spectrometry (MS/MS) coupled with native MS are
      useful for studying noncovalent protein complexes. Collision induced dissociation
      (CID) is the most common MS/MS dissociation method. However, some protein
      complexes, including glycogen phosphorylase B kinase (PHB) and L-glutamate
      dehydrogenase (GDH) examined in this study, are resistant to dissociation by CID
      at the maximum collision energy available in the instrument. Surface induced
      dissociation (SID) was applied to dissociate the two refractory protein
      complexes. Different charge state precursor ions of the two complexes were
      examined by CID and SID. The PHB dimer was successfully dissociated to monomers
      and the GDH hexamer formed trimeric subcomplexes that are informative of its
      quaternary structure. The unfolding of the precursor and the percentages of the
      distinct products suggest that the dissociation pathways vary for different
      charge states. The precursors at lower charge states (+21 for PHB dimer and +27
      for GDH hexamer) produce a higher percentage of folded fragments and dissociate
      more symmetrically than the precusors at higher charge states (+29 for PHB dimer
      and +39 for GDH hexamer). The precursors at lower charge state may be more native
      like than the higher charge state because a higher percentage of folded fragments
      and a lower percentage of highly charged unfolded fragments are detected. The
      combination of SID and charge reduction is shown to be a powerful tool for
      quaternary structure analysis of refractory noncovalent protein complexes, as
      illustrated by the data for PHB dimer and GDH hexamer. 

PMID- 24452297
TI  - ESI mass spectrometric exploration of selective recognition of G-quadruplex in c
      myb oncogene promoter using a novel flexible cyclic polyamide.
AB  - In this research, electrospray ionization mass spectrometry (ESI-MS) was used to
      probe the binding selectivity of a flexible cyclic polyamide (cbeta) to G
      quadruplexes from the long G-rich sequences in the c-myb oncogene promoter. The
      results show that three G-rich sequences, including d[(GGA)3GGTCAC(GGA)4],
      d[(GGA)4GAA(GGA)4], and d[(GGA)3GGTCAC(GGA)4GAA(GGA)4] species in the c-myb
      promoter can form parallel G-quadruplexes, and cbeta selectively binds towards
      these G-quadruplexes over both several other G-quadruplexes and the duplex DNA.
      These properties of cbeta have profound implications on future studies of the
      regulation of c-myb oncogene expression. 

PMID- 24452298
TI  - Understanding gas phase modifier interactions in rapid analysis by differential
      mobility-tandem mass spectrometry.
AB  - A systematic study involving the use and optimization of gas-phase modifiers in
      quantitative differential mobility-mass spectrometry (DMS-MS) analysis is
      presented using nucleoside-adduct biomarkers of DNA damage as an important
      reference point for analysis in complex matrices. Commonly used polar protic and
      polar aprotic modifiers have been screened for use against two deoxyguanosine
      adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N
      (deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8
      PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak
      shapes, and product ion signal intensities while optimizing the DMS-MS
      conditions. The optimized parameters were then applied to rapid quantitation of
      the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct
      levels corresponding to less than one modification in 10(6) normal DNA bases were
      detected using the DMS-MS platform. Based on DMS fundamentals and ab initio
      thermochemical results, we interpret the complexity of DMS modifier responses in
      terms of thermal activation and the development of solvent shells. At very high
      bulk gas temperature, modifier dipole moment may be the most important factor in
      cluster formation and cluster geometry, but at lower temperatures, multi-neutral
      clusters are important and less predictable. This work provides a useful protocol
      for targeted DNA adduct quantitation and a basis for future work on DMS modifier
      effects. 

PMID- 24452299
TI  - Cation-induced stabilization of protein complexes in the gas phase: mechanistic
      insights from hemoglobin dissociation studies.
AB  - Collision-induced dissociation (CID) of electrosprayed protein complexes usually
      involves asymmetric charge partitioning, where a single unfolded chain gets
      ejected that carries a disproportionately large fraction of charge. Using
      hemoglobin (Hb) tetramers as model system, we confirm earlier reports that bound
      metal ions can stabilize protein complexes under CID conditions. We examine the
      mechanism underlying this effect. Nonvolatile salts cause extensive adduct
      formation. Significant stabilization was observed for Mg(2+) and Ca(2+), whereas
      K(+), Rb(+), and Cs(+) had no effect. Precursor ion selection was used to examine
      Hb subpopulations with well-defined metal binding levels. K(+), Rb(+), and Cs(+)
      adducted tetramers eject monomers that carry roughly one-quarter of the metal
      ions that were bound to the precursor. This demonstrates that charge migration
      during CID is exclusively due to proton transfer, not metal ion transfer. Also,
      replacement of highly mobile charge carriers (protons) with less mobile species
      (metal ions) does not exert a stabilizing influence under the conditions used
      here. Interestingly, Hb carrying stabilizing ions (Mg(2+) and Ca(2+)) generates
      monomeric CID products that are metal depleted. This effect is attributed to a
      combination of two factors: (1) Me(2+) binding stabilizes Hb via formation of
      chelation bridges (e.g., R-COO(-) Me(2+) (-)OOC-R); the more Me(2+) a subunit
      contains the more stable it is. (2) More than ~90% of the tetramers contain at
      least one subunit with a below-average number of Me(2+). The prevalence of
      monomeric CID products with depleted Me(2+) levels is caused by the tendency of
      these low metal-containing subunits to undergo preferential unfolding/ejection.

PMID- 24452304
TI  - Oropharyngeal carcinoma in young adults: an alarming national trend.
AB  - OBJECTIVES: To assess the incidence, treatment methods, and outcomes of
      oropharyngeal squamous cell carcinoma (OPSCC) in patients younger than 45 years.
      STUDY DESIGN: Retrospective population based. SETTING: Surveillance Epidemiology
      End Results (SEER) 9 database. SUBJECTS AND METHODS: The SEER 9 database was
      queried from 1973 to 2009 for OPSCC patients <45 years of age. RESULTS: There
      were 1603 patients with OPSCC younger than 45 years. The incidence in patients
      between 36 and 44 years increased from 0.79 to 1.39 (per 100,000). In the same
      time period, there was an increase in the rate from 0.20 to 0.42 in whites and a
      decrease in the rate in African American (AA) patients from 0.67 to 0.32. The
      proportion of grade III/IV tumors also steadily increased from 28% in 1973 to
      1979 to 43% in 2000 to 2009 (P < .0001). Surgery alone was performed in 220
      patients (13.72%) and in combination with radiation therapy in 734 patients
      (45.79%). Five-year survival for the study cohort is 54%. Compared with white
      patients, AA patients had worse survival (P < .0001). Patients who had surgery,
      either alone (localized stage patients) or in combination with radiation, had the
      highest 5-year survival followed by those who had radiation. CONCLUSIONS: There
      was an increase in OPSCC in the study patients within the past 4 decades,
      particularly in those aged 36 to 44 years. Interestingly, the incidence in whites
      increased and in AA patients it decreased. It is important to note that most of
      these patients were treated with surgery, either alone or with radiation therapy.
      The rising incidence within recent decades is thought to be related to human
      papillomavirus transmission and changes in sexual practices.

PMID- 24452306
TI  - Graphene/g-C3N4 bilayer: considerable band gap opening and effective band
      structure engineering.
AB  - The layered graphene/g-C3N4 composites show high conductivity, electrocatalytic
      performance and visible light response and have potential applications in
      microelectronic devices and photocatalytic technology. In the present work, the
      stacking patterns and the correlations between electronic structures and related
      properties of graphene/g-C3N4 bilayers are investigated systematically by means
      of first-principles calculations. Our results indicate that the band gap of
      graphene/g-C3N4 bilayers can be up to 108.5 meV, which is large enough for the
      gap opening at room temperature. The calculated charge density difference
      unravels that the charge redistribution drives the interlayer charge transfer
      from graphene to g-C3N4. Interestingly, the investigation also shows that
      external electric field can tune the band gap of graphene/g-C3N4 bilayers
      effectively. Our research demonstrates that graphene on g-C3N4 with a tunable
      band gap and high carrier mobility may provide a novel way for fabricating high
      performance graphene-based nanodevices. 

PMID- 24452305
TI  - Spin memristive magnetic tunnel junctions with CoO-ZnO nano composite barrier.
AB  - The spin memristive devices combining memristance and tunneling magnetoresistance
      have promising applications in multibit nonvolatile data storage and artificial
      neuronal computing. However, it is a great challenge for simultaneous realization
      of large memristance and magnetoresistance in one nanoscale junction, because it
      is very hard to find a proper spacer layer which not only serves as good
      insulating layer for tunneling magnetoresistance but also easily switches between
      high and low resistance states under electrical field. Here we firstly propose to
      use nanon composite barrier layers of CoO-ZnO to fabricate the spin memristive
      Co/CoO-ZnO/Co magnetic tunnel junctions. The bipolar resistance switching ratio
      is high up to 90, and the TMR ratio of the high resistance state gets to 8% at
      room temperature, which leads to three resistance states. The bipolar resistance
      switching is explained by the metal-insulator transition of CoO(1-v) layer due to
      the migration of oxygen ions between CoO(1-v) and ZnO(1-v).

PMID- 24452307
TI  - A large cohort of patients with hepatocellular carcinoma in a single European
      centre: aetiology and prognosis now and in a historical cohort.
AB  - PRINCIPLES: The incidence of hepatocellular carcinoma is rising. However, this is
      occurring not only in developing nations, but in industrial countries as well.
      Surveillance programmes, classification systems and therapeutic options have
      improved, but there is a lack of data regarding their impact on the prognosis of
      this difficult-to-treat cancer. MATERIALS AND METHODS: We evaluated 484 patients
      and reported on disease stage, therapeutic procedures and survival time. Data
      were compared with a historical cohort treated in the same centre 10 years
      before. RESULTS: In this cohort, the main reason for liver disease was
      alcoholism, although hepatitis B remains the leading cause of hepatocellular
      carcinoma worldwide. Now, most patients have compensated liver function and
      hepatocellular carcinoma is diagnosed in the early tumour stages (it was
      diagnosed in the advanced disease stages in the previous cohort). Overall, median
      survival time was 62.4 weeks, 1-year survival was 58.6% and 3-year survival was
      23.2%. Survival time correlated with the stage of liver disease, tumour stage and
      with therapeutic options. CONCLUSION: Surveillance programmes lead to diagnosis
      in earlier tumour stages. Differentiated classification systems allow
      individualised therapeutic approaches. Earlier cancer stage and compensated liver
      function allow combination or sequential therapy, which was nearly impossible
      some years ago but is an option for most now. Primary liver cancer remains a
      difficult-to-treat malignancy, but the prognosis has improved remarkably, at
      least in the western world.

PMID- 24452308
TI  - [Deep brain stimulation for hyperkinetic movement disorders].
AB  - The term hyperkinetic movement disorder encompasses dystonia, tremor, chorea,
      myoclon and tics. These symptoms are all caused by dysfunctional neural networks
      including the basal ganglia loop and can be accompanied by other neurological or
      psychiatric symptoms. Deep brain stimulation (DBS) is an important extension of
      therapeutic options for this group of patients in whom drug therapy is limited.
      Permanent electrodes are implanted in various subcortical brain areas in order to
      achieve an improvement in motor symptoms by high frequency stimulation. Already
      established indications include primary generalized or segmental dystonia and
      essential tremor but an increasingly better understanding of systemic
      pathophysiology has allowed DBS to be explored as a treatment for other disorders
      of the hyperkinetic spectrum. This article provides an overview of common
      hyperkinetic movement disorders from the viewpoint of recent advances in
      neurostimulation therapy. 

PMID- 24452309
TI  - [Alcohol-induced psychotic disorder--a diagnostic entity of its own?].
AB  - Alcohol-induced psychotic disorders are relatively rare schizophrenia-like
      disorders characterized by key symptoms, such as auditory hallucinations, anxiety
      and delusions while disorders of consciousness and orientation are lacking. The
      diagnostic entity of this disorder has been questioned. Recent findings indicate
      a high risk for rehospitalization and relapse but compared to other drug-induced
      disorders a low risk of schizophrenia-like course of the illness (5 % compared to
      40-50 % with other drugs). Pathophysiological, diagnostic and therapeutic aspects
      of alcohol-induced psychotic disorders are discussed. 

PMID- 24452310
TI  - Female monopolization mediates the relationship between pre- and postcopulatory
      sexual traits.
AB  - Theory predicts a trade-off between investments in precopulatory (ornaments and
      armaments) and postcopulatory (testes and ejaculates) sexual traits due to the
      costs associated with their growth and maintenance within the finite energy
      resources available. Empirical studies, however, have revealed considerable
      inconsistency in the strength and direction of relationships among these sexual
      traits. Ambiguity may result from variance in the marginal benefits gained by
      increasing investments in either pre- or postcopulatory sexual traits. Here, in a
      broad comparative study, we test the prediction that the relationship between pre
      and postcopulatory sexual traits differs among taxa relative to the importance
      of male-male contest competition within them. We find that covariance between pre
      and postcopulatory sexual traits gradually shifts from strongly positive to
      strongly negative with increasing male-male contest competition. Thus, our
      findings reveal a potentially unifying explanation for the oftentimes
      inconsistent relationships in the strength and direction of covariance among
      sexual traits. 

PMID- 24452311
TI  - Share information about patients to tackle static suicide rate, doctors are told.

PMID- 24452312
TI  - Transformylating amine with DMF to formamide over CeO2 catalyst.
AB  - We here report a new protocol for the formylation of various amines, primary or
      secondary, aromatic or alkyl, cyclic or linear, mono- or di-amine, with
      dimethylformamide (DMF) as the formylation reagent to obtain the corresponding
      formamides in good to excellent yields over CeO2 catalyst. The reaction requires
      no homogeneous acidic or basic additives and is tolerant to water. 

PMID- 24452313
TI  - Fabrication of magnetically separable fluorescent terbium-based MOF nanospheres
      for highly selective trace-level detection of TNT.
AB  - In this work, we present novel kinds of Fe3O4@Tb-BTC magnetic metal-organic
      framework (MOF) nanospheres which possess both magnetic characteristics and
      fluorescent properties using a layer by layer assembly technique. The structure
      and morphology of the as-prepared Fe3O4@Tb-BTC were systematically characterized
      and it was applied in detection of nitroaromatic explosives, such as 2,4
      dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2-nitrotoluene (2-NT), 4
      nitrotoluene (4-NT), nitrobenzene (NB) and picric acid (PA). The results indicate
      that the fluorescence intensity of Fe3O4@Tb-BTC can be quenched by all analytes
      studied in the present work. Remarkably, the as-synthesized nanospheres exhibit
      high sensitivity for 2,4,6-trinitrotoluene (TNT) detection with Ksv value of (94
      800 M(-1)). Besides, the magnetic nanospheres can be easily recycled, which makes
      it more convenient for reutilization and friendly to the environment. The results
      show that it has broad application prospects in the detection of nitroaromatic
      explosives. 

PMID- 24452314
TI  - Thrombolysis for acute deep vein thrombosis.
AB  - BACKGROUND: Standard treatment for deep vein thrombosis aims to reduce immediate
      complications. Use of thrombolysis or clot dissolving drugs could reduce the long
      term complications of post-thrombotic syndrome (PTS) (pain, swelling, skin
      discolouration, or venous ulceration) in the affected leg. This is the second
      update of a review first published in 2004. OBJECTIVES: To assess the effects of
      thrombolytic therapy and anticoagulation versus anticoagulation in the management
      of people with acute deep vein thrombosis (DVT) of the lower limb as determined
      by the effects on pulmonary embolism, recurrent venous thromboembolism, major
      bleeding, post-thrombotic complications, venous patency and venous function.
      SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group
      Trials Search Co-ordinator searched the Specialised Register (last searched April
      2013) and CENTRAL (2013, Issue 4). SELECTION CRITERIA: Randomised controlled
      trials (RCTs) examining thrombolysis and anticoagulation versus anticoagulation
      for acute DVT were considered. DATA COLLECTION AND ANALYSIS: In the previous
      review of 2010, one review author (LW) selected trials, extracted data and
      assessed study quality, with checking at all stages by the other review author
      (MPA). If necessary, we sought additional information from trialists. For this
      update (2013), LW and CB selected trials, extracted data independently, and
      sought advice from MPA where necessary. All studies, existing and new, required
      full risk of bias assessment in line with current Cochrane procedures. Two of LW,
      CB and MA independently assessed risk of bias with discussion with the third
      author where necessary. MAIN RESULTS: Seventeen studies with 1103 participants
      were included. Complete clot lysis occurred significantly more often in the
      treatment group in early follow up (risk ratio (RR) 4.91; 95% confidence interval
      (CI) 1.66 to 14.53, P = 0.004) and at intermediate follow up (RR 2.37; 95% CI
      1.48 to 3.80, P = 0.0004). A similar effect was seen for any degree of
      improvement in venous patency. Significantly less PTS occurred in those receiving
      thrombolysis, (RR 0.64; 95% CI 0.52 to 0.79, P < 0.0001). Leg ulceration was
      reduced although the data were limited by small numbers (RR 0.48; 95% CI 0.12 to
      1.88, P = 0.29). Those receiving thrombolysis had significantly more bleeding
      complications (RR 2.23; 95% CI 1.41 to 3.52, P = 0.0006). Three strokes occurred
      in the treatment group, all in trials conducted pre-1990, and none in the control
      group. There was no significant effect on mortality detected at either early or
      intermediate follow up. Data on the occurrence of pulmonary embolism (PE) and
      recurrent DVT were inconclusive. Systemic thrombolysis is now not commonly used
      and catheter-directed thrombolysis (CDT) is the more favoured means of
      administration. This has been studied in iliofemoral DVT, and results from two
      trials are consistent with those from trials of systemic thrombolysis in DVT at
      other levels of occlusion. AUTHORS' CONCLUSIONS: Thrombolysis increases the
      patency of veins and reduces the incidence of PTS following proximal DVT by a
      third. Strict eligibility criteria are necessary to reduce the risk of bleeding
      complications and this limits the applicability of this treatment. In those who
      are treated there is a small increased risk of bleeding. In recent years CDT is
      the most studied route of administration, and results appear to be similar to
      systemic administration.

PMID- 24452315
TI  - Forkhead-box A1 suppresses the progression of endometrial cancer via crosstalk
      with estrogen receptor alpha.
AB  - Mechanisms governing the function of Forkhead-box A1 (FOXA1), a member of the FOX
      class of transcription factors, have been extensively studied. However, little is
      known about the activities and expression pattern of FOXA1 in endometrial cancer
      (EC). In the present study, we investigated the level of FOXA1 in multiple human
      EC cell lines and clinical samples by immunohistochemistry, qRT-PCR and Western
      blot analysis. FOXA1 overexpression was observed in estrogen receptor (ER)alpha
      positive EC cell lines (P=0.0048). In endometrial tissues, FOXA1 was
      significantly upregulated in both normal endometrium and well-differentiated
      endometrial cancer tissues (P<0.001). Functional analyses of FOXA1 were evaluated
      by MTT, plate colony formation and Transwell assay. The results revealed that
      forced expression of FOXA1 inhibited EC cell proliferation, whereas FOXA1
      depletion promoted cell viability and was associated with tumorigenesis. The nude
      mouse tumor xenograft assay also confirmed that ablation of FOXA1 expression
      promoted cell proliferation. Furthermore, we found that knockdown of FOXA1
      decreased the expression of ERalpha, and FOXA1 interacted with this receptor in
      the EC cell lines. Collectively, these experiments suggest that FOXA1 is a tumor
      suppressor in EC and has a possible interaction with ERalpha. 

PMID- 24452316
TI  - Variable clinical expressivity of STAT3 mutation in hyperimmunoglobulin E
      syndrome: genetic and clinical studies of six patients.
AB  - BACKGROUND AND PURPOSE: Autosomal dominant Hyper IgE syndrome (AD-HIES) is a rare
      and complex primary immunodeficiency that affects multiple systems. Mutations in
      signal transducer and activator of transcription 3 (STAT3) gene cause AD-HIES.
      These mutations have a dominant-negative effect and the presence of such
      mutations is associated with a clinical phenotype. We aim to describe genetic and
      clinical characteristics of patients with AD-HIES in our clinic and to highlight
      the variability of clinical patterns in the same family. METHODS: We describe six
      patients, four individuals of the same family and two unrelated patients. All
      patients were given a clinical score based on disease phenotype according to the
      National Institute of Health (NIH) score. Mutation analysis of STAT3 was done by
      PCR amplification of all coding exons followed by bidirectional sequencing using
      the BigDye kit v1.1 and an ABI3700 genetic analyzer (Applied Biosystems).
      RESULTS: All six patients had DNA binding region point mutations: a proband and
      his three children with p.Phe384Leu mutation, a patient with p.Arg382Trp
      substitution and a patient with p.Arg382Gln mutation. All of these mutations were
      previously reported. Patients differed in infectious, immunologic and somatic
      features. We observed an extreme variability in disease phenotype within the
      reported family with one genetically affected patient displaying an 'unaffected'
      phenotype. CONCLUSIONS: Although the genetic cause of AD-HIES is known, more
      studies are required to better understand the possible additional factors that
      may affect disease expressivity within families and the clinical diversity of the
      disease.

PMID- 24452317
TI  - Mechanical thrombectomy in basilar artery thrombosis: technical advances and
      safety in a 10-year experience.
AB  - PURPOSE: Multiple endovascular devices have been used for mechanical thrombectomy
      (MT) in basilar artery occlusion (BAO) for >10 years. Based on a single-center
      experience during the course of one decade, we present data on safety and
      efficacy of previous MT devices compared with modern stent retriever and suction
      thrombectomy. MATERIALS AND METHODS: Eighty-one patients (29 women, 52 men, mean
      age 61.5 years, range 17-90) with angiographically confirmed BAO that had been
      treated by MT between 2001 and 2011 were retrospectively evaluated. Patients in
      group 1 (n = 60) had been treated between 2001 and 2008 with different devices
      available at that time. Patients in group 2 (n = 21) had been treated by modern
      stent retriever or local suction devices between 2008 and 2011. Recanalization
      rate, needle to recanalization time, procedure-related complications, and distal
      embolization of thrombotic material were recorded and compared. RESULTS:
      Recanalization rates of 95% were high in both groups. Procedure-related
      dissection (n = 5) and subarachnoid hemorrhage (n = 9) occurred in group 1 but
      not in group 2 (p < 0.016). Needle-to-recanalization time was less than half in
      group 2 compared with group 1 (54.6 vs. 132.3 min, p < 0.01). Frequency of distal
      embolization was comparable in both groups (47%). CONCLUSION: High recanalization
      rates have been achieved since the introduction of MT in BAO. However, modern
      stent retriever and suction devices allow for safer and more rapid recanalization
      compared with previous MT devices.

PMID- 24452319
TI  - High-pitch carbon dioxide contrasted CT angiography: pilot study.
AB  - PURPOSE: This study was designed to evaluate CO2 computed tomography angiography
      (CO2-CTA) of the iliac and lower limb arteries in patients with contraindications
      for iodinated contrast agent (ICA). METHODS: Five patients with contraindications
      for ICA were examined using CO2-fluoroscopic enhanced angiography (CO2-FLA) and
      CO2-CTA using a high-pitch examination protocol. Objective (vessel diameter) and
      subjective (visual score) image quality parameters were evaluated. Pathological
      findings in both modalities were compared. RESULTS: CO2-CTA was feasible in all
      patients without adverse side effects, except for CO2 injection-associated pain.
      Objective vessel analysis revealed no significant difference in diameters as
      determined by CO2-CTA and CO2-FLA (0.44 +/- 0.4 and 0.46 +/- 0.41 mm, p = 0.93).
      CO2-CTA had on average a higher image-quality score (2.6 +/- 1.0 vs. 2.3 +/- 1.0,
      p = 0.009). While for pelvic and upper leg CO2-CTA advantageous (3.1 +/- 0.74 vs.
      2.7 +/- 0.9, p = 0.0014) at good quality scores, for calf vessels no significant
      improvement was visible (1.9 +/- 1.0 vs. 1.7 +/- 0.9, p = 0.49) and scores were
      poorer. CONCLUSIONS: CO2-CTA with high-pitch CT was feasible in a limited number
      of patients. Image-quality scores were on average higher for CO2-CTA than for CO2
      FLA, while limited imaging quality in the vessels below the knee needs further
      work on the CT protocol. An added value of cross-sectional imaging was apparent
      but needs further quantification.

PMID- 24452318
TI  - Role for putative hepatocellular carcinoma stem cell subpopulations in biological
      response to incomplete thermal ablation: in vitro and in vivo pilot study.
AB  - PURPOSE: To investigate the potential role for CD44(+) and CD90(+) hepatocellular
      carcinoma (HCC) cellular subpopulations in biological response to thermal
      ablation-induced heat stress. METHODS: This study was approved by the
      institutional animal care committee. The N1S1 rat HCC cell line was subjected to
      sublethal heat stress (45  degrees C) or control (37  degrees C) for 10 min,
      costained with fluorescent-labeled antibodies against CD44, CD90, and 7-AAD after
      a 48-h recovery and analyzed by flow cytometry to assess the percentage of live
      CD44(+) and CD90(+) HCC cells (n = 4). Experiments were repeated with
      pretreatment of N1S1 cells with a dose titration of the dual PI3K-mTOR inhibitor
      BEZ235 or vehicle control (n = 3). Rats bearing orthotopic N1S1 tumors were
      subjected to ultrasound-guided partial laser ablation (n = 5) or sham ablation (n
      = 3), euthanized 24 h after ablation, and liver/tumor analyzed for
      immunohistochemical staining of CD44 and CD90. Differences between groups were
      compared with an unpaired t test. RESULTS: Sublethal heat stress induced a
      significant increase in the relative proportion of live CD44(+) and CD90(+) HCC
      cells compared to the control group: CD44(+)CD90(-) (5.3-fold; p = 0.0001), CD44(
      )CD90(+) (2.4-fold; p = 0.003), and CD44(+)CD90(+) (22.0-fold; p < 0.03).
      Inhibition of PI3K-mTOR prevented heat stress-induced enrichment of the
      population of live CD44(+) HCC cells (p < 0.01), but not CD90(+) cells (p >
      0.10). Immunohistochemical analysis demonstrated preferential localization of
      clusters of CD44(+) cells at both the tumor margin and ablation margin.
      CONCLUSION: These studies provide experimental evidence supporting a role for HCC
      cells expressing the putative stem cell marker CD44 in HCC response to heat
      stress.

PMID- 24452321
TI  - A case of vulval ulceration.

PMID- 24452320
TI  - Percutaneous balloon dilatation and long-term drainage as treatment of
      anastomotic and nonanastomotic benign biliary strictures.
AB  - PURPOSE: This study was designed to determine the effectiveness of percutaneous
      balloon dilation and long-term drainage of postoperative benign biliary
      strictures. METHODS: Medical records of patients with postoperative benign
      biliary strictures, in whom percutaneous transhepatic biliary drainage (PTBD) and
      balloon dilation was performed between January 1999 and December 2011, were
      retrospectively reviewed. PTBD and balloon dilation (4-10 mm) were followed by
      placement of internal-external biliary drainage catheters (8.5-12 F). Patients
      were scheduled for elective tube changes, if necessary combined with repeated
      balloon dilation of the stenosis, at 3-week intervals up to a minimum of 3
      months. RESULTS: Ninety-eight patients received a total of 134 treatments. The
      treatment was considered technically successful in 98.5%. Drainage catheters were
      left in with a median duration of 14 weeks. Complications occurred in 11
      patients. In 13 patients, percutaneous treatment was converted to surgical
      intervention. Of 85 patients in whom percutaneous treatment was completed, 11.8%
      developed clinically relevant restenosis. Median follow-up was 35 months.
      Probability of patency at 1, 2, 5, and 10 years was 0.95, 0.92, 0.88, and 0.72,
      respectively. Overall, 76.5% had successful management with PTBD. Restenosis and
      treatment failure occurred more often in patients who underwent multiple
      treatments. Treatments failed more often in patients with multiple strictures.
      All blood markers of liver function significantly decreased to normal values.
      CONCLUSIONS: Percutaneous balloon dilation and long-term drainage demonstrate
      good short- and long-term effectiveness as treatment for postoperative benign
      biliary strictures with an acceptably low complication rate and therefore are
      indicated as treatment of choice.

PMID- 24452322
TI  - A new Australian online and phone mental health support service for young people
      living with cancer.
AB  - OBJECTIVE: The purpose of CanTeen's E-Mental Health Service for Young People
      Living With Cancer (YPLWC) is to meet the unique psychosocial needs of young
      people (12-24 years) in Australia impacted by cancer (either as a patient or
      family member of someone with cancer). CONCLUSIONS: This online platform will
      provide the primary site where all YPLWC can find information, connect with
      others going through a similar experience, express their feelings, utilise tools
      for support and access professional psychosocial support services that will meet
      their individual needs. The overall outcome of the service will be to ensure that
      the YPLWC visiting the site experience optimal psychological wellbeing.
      Ultimately, the service's value will be in improving the lives of young people
      who engage with it and the follow-on effect that this will have on their families
      and communities in the long-term.

PMID- 24452323
TI  - Effect of opening middle-ear cavity on vibrations of gerbil tympanic membrane.
AB  - This paper presents in vivo experimental measurements of vibrations on the pars
      flaccida, along the manubrium and at several points on the pars tensa in the
      gerbil with open middle-ear cavity. The effects of progressive opening of the
      middle-ear cavity are presented, with up to five different extents of opening. In
      all manubrial, pars-tensa and pars-flaccida responses, opening the cavity causes
      an increase in the low-frequency magnitude and a shift of the main middle-ear
      resonance to lower frequencies and introduces an antiresonance. However, opening
      the cavity has little or no effect on either the mode of vibration of the
      manubrium or the breakup frequency of the pars tensa. When the opening is
      gradually widened, the antiresonance frequency moves to higher frequencies. When
      the opening is made as wide as anatomically possible, the antiresonance moves to
      almost 10 kHz. The main increase in the low-frequency response magnitude happens
      upon making the smallest hole in the cavity wall, and further progressive
      enlarging of the opening has little or no effect on the low-frequency magnitude.
      The antiresonance interferes with the response shapes. An identification method
      is suggested for eliminating the effect of the antiresonance in order to estimate
      the ideal open-cavity response. The method is validated and then applied to
      manubrial and pars-tensa responses. Estimating the ideal open-cavity responses
      will simplify comparison of the data with numerical models which do not include
      the air cavity. The data collected at intermediate stages of opening will be
      useful in validating models that do include the cavity.

PMID- 24452324
TI  - Musashi-1 expression and clinicopathological significance in young gastric cancer
      patients: a matched case-control study.
AB  - Musashi-1 (Msi-1) is proposed to be a marker of progenitor cells in the human
      gastric mucosa. We examined Msi-1 expression and localization in surgical
      specimens of gastric cancer in young patients using immunohistochemistry and
      tested associations of Msi-1 expression with clinicopathological features.
      Patients (n=611) with gastric cancer who underwent radical gastrectomy were
      included in the present study. To minimize confounding effects, we matched 26
      gastric cancer patients 30 years of age or younger (age <=30) with 26 patients 60
      years of age or older (age >=60). The groups were matched by gender, tumor
      histological type and tumor stage. Gastric cancer in the younger patients was
      significantly associated with female gender and with diffuse histological type,
      compared with 585 gastric cancer patients older than 31 years. Msi-1 expression
      was more frequently upregulated in gastric cancer in young patients than in
      patients older than 60 years. Msi-1 expression was significantly associated with
      diffuse histological type, depth of tumor invasion, lymph node metastasis and
      tumor stage in the 26 young patients with gastric cancer. Univariate Kaplan-Meier
      survival analysis identified Msi-1 expression as a significantly negative factor
      in the survival of young gastric cancer patients. However, Msi-1 expression was
      not significantly associated with survival in the 26 matched older patients.
      According to mucin phenotype, the gastric foveolar type predominated in Msi-1
      positive gastric cancers. Our principal findings included a significantly higher
      level of Msi-1 expression in younger gastric cancer patients compared to older
      ones, and a probable association of tumor Msi-1 expression in young gastric
      cancer patients with more aggressive tumor type.

PMID- 24452325
TI  - Detection of skeletal muscle metastases on initial staging of lung cancer: a
      retrospective case series.
AB  - PURPOSE: Estimation of skeletal muscle metastases (SMMs) at the time of diagnosis
      and/or initial staging of lung cancer. MATERIALS AND METHODS: Retrospective
      evaluation of clinical charts and imaging data suggestive of SMMs of patients
      with histology-proved lung cancer over a 5-year period. RESULTS: SMMs were
      identified in 46 out of 1,754 patients. Single and multiple (62.9% of cases) SMMs
      were detected by total body multi-detector computed tomography (MDCT). They were
      associated with poorly differentiated (43%) and advanced adenocarcinomas (52%)
      without clinically relevant symptoms and/or signs. Psoas and buttock muscles were
      most frequently involved (33.3%). MDCT findings consisted of well-defined
      homogeneously hyperdense oval masses (31%), lesions with ring-like enhancement
      and central hypoattenuation (68%), or large abscess-like necrotic lesions (24%).
      Sonography revealed well-defined hypoechoic masses (41.6%), ill-defined
      hypoechoic lesions (33.3%), or anechoic areas with a necrotic centre (25%).
      Positron emission tomography revealed that all SMMs were metabolically active.
      CONCLUSIONS: SMMs are uncommon but not negligible in lung cancer, with an
      estimated prevalence of 2.62% in our series. Although histology remains the
      recommended method, use of high-performance imaging techniques and increased
      clinical suspicion may improve their early detection. Efforts addressing their
      effect on the natural history of lung cancer are needed.

PMID- 24452326
TI  - Muscle involvement in two Behcet cases: magnetic resonance imaging and histology
      findings.
AB  - Behcet's disease (BD) is a systemic vasculitis with a classic trio of symptoms of
      oral aphthous ulcers, genital ulcers, and ocular lesions that present in a
      relapsing fashion. Despite these most frequently encountered symptoms of the
      disease, other systems such as vascular, gastrointestinal, and neurological
      involvements can also occur. Muscular involvement is rare, and there are only a
      few cases in the literature, which were reported mainly in a pediatric
      population. In this two-adult case report, muscular involvement of BD with an
      emphasis on magnetic resonance imaging and histology findings will be presented. 

PMID- 24452327
TI  - Liver and systemic insulin resistance.

PMID- 24452328
TI  - Developing a framework for evaluating kidney transplantation candidacy in
      children with multiple comorbidities.
AB  - Children with multiple comorbidities, including neurodevelopmental delay, can
      develop end-stage kidney disease (ESKD). When and if these children should be
      eligible for kidney transplantation is an area of debate within the pediatric
      nephrology community and the public. Discussions focus on expected survival and
      quality of life posttransplant, as well as resource allocation decisions, as
      donor kidneys remain a limited resource. This paper focuses on the evidence
      available regarding outcomes in this population and the ethical issues that
      should be considered. The authors offer a framework for transplant teams
      evaluating children with comorbidities for kidney transplant, focusing on the
      benefits and burdens that transplantation can be expected to achieve. 

PMID- 24452330
TI  - Thirty-three years of progress: the International Workshops on Developmental
      Nephrology and the role of IPNA.

PMID- 24452329
TI  - miRNAs in mammalian ureteric bud development.
AB  - The collecting duct network and the urothelium of the ureter of the metanephric
      kidney are derived from the ureteric bud epithelium, initially an outgrowth from
      the caudal end of the Wolffian duct at the onset of the metanephric kidney
      development. The tips of the ureteric bud epithelium undergo reiterative
      branching morphogenesis, which generates more tips and trunks, whereas the
      ureteric trunks grow and differentiate into principal cells and intercalated
      cells of the collecting ducts that regulate body water and acid-base homeostasis.
      microRNAs (miRNAs) are a family of small non-coding RNAs that regulate a
      diversity of biological processes including organogenesis, mostly by negatively
      regulating their target gene expression. In this review, I will summarize the
      current knowledge on the critical roles of miRNAs expressed in the ureteric bud
      epithelium in ureteric bud morphogenesis and differentiation, including ureteric
      bud branching morphogenesis, collecting duct terminal differentiation,
      cystogenesis of the collecting ducts, and ureter development. 

PMID- 24452332
TI  - Transgenic Brassica juncea plants expressing MsrA1, a synthetic cationic
      antimicrobial peptide, exhibit resistance to fungal phytopathogens.
AB  - Cationic antimicrobial peptides (CAPs) have shown potential against broad
      spectrum of phytopathogens. Synthetic versions with desirable properties have
      been modeled on these natural peptides. MsrA1 is a synthetic chimera of cecropin
      A and melittin CAPs with antimicrobial properties. We generated transgenic
      Brassica juncea plants expressing the msrA1 gene aimed at conferring fungal
      resistance. Five independent transgenic lines were evaluated for resistance to
      Alternaria brassicae and Sclerotinia sclerotiorum, two of the most devastating
      pathogens of B. juncea crops. In vitro assays showed inhibition by MsrA1 of
      Alternaria hyphae growth by 44-62 %. As assessed by the number and size of
      lesions and time taken for complete leaf necrosis, the Alternaria infection was
      delayed and restricted in the transgenic plants with the protection varying from
      69 to 85 % in different transgenic lines. In case of S. sclerotiorum infection,
      the lesions were more severe and spread profusely in untransformed control
      compared with transgenic plants. The sclerotia formed in the stem of
      untransformed control plants were significantly more in number and larger in size
      than those present in the transgenic plants where disease protection of 56-71.5 %
      was obtained. We discuss the potential of engineering broad spectrum biotic
      stress tolerance by transgenic expression of CAPs in crop plants. 

PMID- 24452331
TI  - Molecular and functional characterization of an invertase secreted by Ashbya
      gossypii.
AB  - The repertoire of hydrolytic enzymes natively secreted by the filamentous fungus
      Ashbya (Eremothecium) gossypii has been poorly explored. Here, an invertase
      secreted by this flavinogenic fungus was for the first time molecularly and
      functionally characterized. Invertase activity was detected in A. gossypii
      culture supernatants and cell-associated fractions. Extracellular invertase
      migrated in a native polyacrylamide gel as diffuse protein bands, indicating the
      occurrence of at least two invertase isoforms. Hydrolytic activity toward sucrose
      was approximately 10 times higher than toward raffinose. Inulin and levan were
      not hydrolyzed. Production of invertase by A. gossypii was repressed by the
      presence of glucose in the culture medium. The A. gossypii invertase was
      demonstrated to be encoded by the AFR529W (AgSUC2) gene, which is highly
      homologous to the Saccharomyces cerevisiae SUC2 (ScSUC2) gene. Agsuc2 null
      mutants were unable to hydrolyze sucrose, proving that invertase is encoded by a
      single gene in A. gossypii. This mutation was functionally complemented by the
      ScSUC2 and AgSUC2 genes, when expressed from a 2-MUm-plasmid. The signal
      sequences of both AgSuc2p and ScSuc2p were able to direct the secretion of
      invertase into the culture medium in A. gossypii. 

PMID- 24452333
TI  - Transgenic expression of Map3k4 rescues T-associated sex reversal (Tas) in mice.
AB  - Disorders of sex development in the human population range in severity from mild
      genital defects to gonadal sex reversal. XY female development has been
      associated with heterozygous mutations in several genes, including SOX9, WT1 and
      MAP3K1. In contrast, XY sex reversal in mice usually requires complete absence of
      testis-determining gene products. One exception to this involves T-associated sex
      reversal (Tas), a phenomenon characterized by the formation of ovotestes or
      ovaries in XY mice hemizygous for the hairpin-tail (T(hp)) or T-Orleans (T(Orl))
      deletions on proximal mouse chromosome 17. We recently reported that mice
      heterozygous for a null allele of Map3k4, which resides in the T(hp) deletion,
      exhibit XY ovotestis development and occasional gonadal sex reversal on the
      sensitized C57BL/6J-Y(AKR) (B6-Y(AKR)) genetic background, reminiscent of the Tas
      phenotype. However, these experiments did not exclude the possibility that loss
      of other loci in the T(hp) deletion, or other effects of the deletion itself,
      might contribute to Tas. Here, we show that disruption to Sry expression
      underlies XY gonadal defects in B6-Y(AKR) embryos harbouring the T(hp) deletion
      and that a functional Map3k4 bacterial artificial chromosome rescues these
      abnormalities by re-establishing a normal Sry expression profile. These data
      demonstrate that Map3k4 haploinsufficiency is the cause of T-associated sex
      reversal and that levels of this signalling molecule are a major determinant of
      the expression profile of Sry. 

PMID- 24452334
TI  - Glycogen accumulation underlies neurodegeneration and autophagy impairment in
      Lafora disease.
AB  - Lafora disease is a fatal neurodegenerative condition characterized by the
      accumulation of abnormal glycogen inclusions known as Lafora bodies. It is an
      autosomal recessive disorder caused by mutations in either the laforin or malin
      gene. To study whether glycogen is primarily responsible for the
      neurodegeneration in Lafora disease, we generated malin knockout mice with
      impaired (totally or partially) glycogen synthesis. These animals did not show
      the increase in markers of neurodegeneration, the impairments in
      electrophysiological properties of hippocampal synapses, nor the susceptibility
      to kainate-induced epilepsy seen in the malin knockout model. Interestingly, the
      autophagy impairment that has been described in malin knockout animals was also
      rescued in this double knockout model. Conversely, two other mouse models in
      which glycogen is over-accumulated in the brain independently of the lack of
      malin showed impairment in autophagy. Our findings reveal that glycogen
      accumulation accounts for the neurodegeneration and functional consequences seen
      in the malin knockout model, as well as the impaired autophagy. These results
      identify the regulation of glycogen synthesis as a key target for the treatment
      of Lafora disease.

PMID- 24452335
TI  - Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of
      onset in Huntington's disease.
AB  - Huntington's disease (HD) is a devastating neurodegenerative disorder which is
      inherited in an autosomal dominant manner. HD is caused by a trinucleotide CAG
      repeat expansion that encodes a polyglutamine stretch in the huntingtin (HTT)
      protein. Mutant HTT expression leads to a myriad of cellular dysfunctions
      culminating in neuronal loss and consequent motor, cognitive and psychiatric
      disturbances in HD patients. The length of the CAG repeat is inversely correlated
      with age of onset (AO) in HD patients, while environmental and genetic factors
      can further modulate this parameter. Here, we explored whether the recently
      described copy-number variation (CNV) of the gene SLC2A3-which encodes the
      neuronal glucose transporter GLUT3-could modulate AO in HD. Strikingly, we found
      that increased dosage of SLC2A3 delayed AO in an HD cohort of 987 individuals,
      and that this correlated with increased levels of GLUT3 in HD patient cells. To
      our knowledge this is the first time that CNV of a candidate gene has been found
      to modulate HD pathogenesis. Furthermore, we found that increasing dosage of
      Glut1-the Drosophila melanogaster homologue of this glucose transporter
      ameliorated HD-relevant phenotypes in fruit flies, including neurodegeneration
      and life expectancy. As alterations in glucose metabolism have been implicated in
      HD pathogenesis, this study may have important therapeutic relevance for HD.

PMID- 24452337
TI  - Population variation in and selection for resistance to pyrethroid-neonicotinoid
      insecticides in the bed bug.
AB  - Pyrethroid resistance in bed bugs, Cimex lectularius, has prompted a change to
      combination products that include a pyrethroid and a neonicotinoid. Ten
      populations of bed bugs were challenged with two combination products (Temprid SC
      and Transport GHP). Susceptibility of these populations varied, with the
      correlated response of the two products indicating cross resistance. We imposed
      selection on three populations using label rate Temprid, and then reared progeny
      from unselected and selected strains. All selected strains were significantly
      less susceptible to Temprid SC than unselected strains. Temprid selected strains
      were also less susceptible to Transport. The pyrethroid component of Temprid
      showed a significantly higher LD50 in selected strains, but susceptibility to the
      neonicotinoid remained unchanged. Taken together these results indicate
      resistance to combination insecticides is present in field populations at levels
      that should be of concern, and that short-term selection affecting existing
      variance in susceptibility can quickly increase resistance. 

PMID- 24452338
TI  - Gastrointestinal bleeding associated with rivaroxaban administration in a treated
      patient infected with human immunodeficiency virus.
AB  - The use of rivaroxaban in fixed dosing regimens without need for routine
      coagulation monitoring may lead to the misconception that there is a minimal risk
      of drug-drug interactions. We describe the case of a patient infected with human
      immunodeficiency virus (HIV) on salvage therapy who developed gastrointestinal
      bleeding while receiving the standard dose of rivaroxaban for the prevention of
      venous thromboembolism after surgery. This case clearly sends a warning that
      protease inhibitors should not be co-administered with rivaroxaban. Furthermore,
      it highlights the importance of clinicians' caution about potential drug-drug
      interactions. 

PMID- 24452336
TI  - Human skeletal muscle xenograft as a new preclinical model for muscle disorders.
AB  - Development of novel therapeutics requires good animal models of disease.
      Disorders for which good animal models do not exist have very few drugs in
      development or clinical trial. Even where there are accepted, albeit imperfect
      models, the leap from promising preclinical drug results to positive clinical
      trials commonly fails, including in disorders of skeletal muscle. The main
      alternative model for early drug development, tissue culture, lacks both the
      architecture and, usually, the metabolic fidelity of the normal tissue in vivo.
      Herein, we demonstrate the feasibility and validity of human to mouse xenografts
      as a preclinical model of myopathy. Human skeletal muscle biopsies transplanted
      into the anterior tibial compartment of the hindlimbs of NOD-Rag1(null)
      IL2rgamma(null) immunodeficient host mice regenerate new vascularized and
      innervated myofibers from human myogenic precursor cells. The grafts exhibit
      contractile and calcium release behavior, characteristic of functional muscle
      tissue. The validity of the human graft as a model of facioscapulohumeral
      muscular dystrophy is demonstrated in disease biomarker studies, showing that
      gene expression profiles of xenografts mirror those of the fresh donor biopsies.
      These findings illustrate the value of a new experimental model of muscle
      disease, the human muscle xenograft in mice, as a feasible and valid preclinical
      tool to better investigate the pathogenesis of human genetic myopathies and to
      more accurately predict their response to novel therapeutics.

PMID- 24452339
TI  - Believing in seeing.

PMID- 24452340
TI  - Optical excitation of thin magnetic layers in multilayer structures.

PMID- 24452341
TI  - Reply to 'Optical excitation of thin magnetic layers in multilayer structures'.

PMID- 24452342
TI  - On the thermodynamics of light trapping in solar cells.

PMID- 24452343
TI  - Reply to 'On the thermodynamics of light trapping in solar cells'.

PMID- 24452344
TI  - Tracking gene and cell fate for therapeutic gain.

PMID- 24452351
TI  - Nanoscale friction: Distorted by the tip.

PMID- 24452345
TI  - A targeted approach to cancer imaging and therapy.

PMID- 24452352
TI  - Thermoelectric polymers: Behind organics' thermopower.

PMID- 24452353
TI  - Nanoparticle crystallization: DNA-bonded 'atoms'.

PMID- 24452354
TI  - Cancer imaging: Lighting up tumours.

PMID- 24452355
TI  - Material witness: No substitute.

PMID- 24452357
TI  - Flat optics with designer metasurfaces.
AB  - Conventional optical components such as lenses, waveplates and holograms rely on
      light propagation over distances much larger than the wavelength to shape
      wavefronts. In this way substantial changes of the amplitude, phase or
      polarization of light waves are gradually accumulated along the optical path.
      This Review focuses on recent developments on flat, ultrathin optical components
      dubbed 'metasurfaces' that produce abrupt changes over the scale of the free
      space wavelength in the phase, amplitude and/or polarization of a light beam.
      Metasurfaces are generally created by assembling arrays of miniature, anisotropic
      light scatterers (that is, resonators such as optical antennas). The spacing
      between antennas and their dimensions are much smaller than the wavelength. As a
      result the metasurfaces, on account of Huygens principle, are able to mould
      optical wavefronts into arbitrary shapes with subwavelength resolution by
      introducing spatial variations in the optical response of the light scatterers.
      Such gradient metasurfaces go beyond the well-established technology of frequency
      selective surfaces made of periodic structures and are extending to new spectral
      regions the functionalities of conventional microwave and millimetre-wave
      transmit-arrays and reflect-arrays. Metasurfaces can also be created by using
      ultrathin films of materials with large optical losses. By using the controllable
      abrupt phase shifts associated with reflection or transmission of light waves at
      the interface between lossy materials, such metasurfaces operate like optically
      thin cavities that strongly modify the light spectrum. Technology opportunities
      in various spectral regions and their potential advantages in replacing existing
      optical components are discussed. 

PMID- 24452356
TI  - Imaging macrophages with nanoparticles.
AB  - Nanomaterials have much to offer, not only in deciphering innate immune cell
      biology and tracking cells, but also in advancing personalized clinical care by
      providing diagnostic and prognostic information, quantifying treatment efficacy
      and designing better therapeutics. This Review presents different types of
      nanomaterial, their biological properties and their applications for imaging
      macrophages in human diseases, including cancer, atherosclerosis, myocardial
      infarction, aortic aneurysm, diabetes and other conditions. We anticipate that
      future needs will include the development of nanomaterials that are specific for
      immune cell subsets and can be used as imaging surrogates for nanotherapeutics.
      New in vivo imaging clinical tools for noninvasive macrophage quantification are
      thus ultimately expected to become relevant to predicting patients' clinical
      outcome, defining treatment options and monitoring responses to therapy. 

PMID- 24452360
TI  - Photocurrent spectroscopic studies of diketopyrrolopyrrole-based statistical
      copolymers.
AB  - Diketopyrrolopyrrole (DPP) containing copolymers have gained a lot of interest in
      organic optoelectronics with great potential in organic photovoltaics. In this
      work, DPP based statistical copolymers, with slightly different bandgap energies
      and a varying fraction of donor-acceptor ratio are investigated using
      monochromatic photocurrent spectroscopy and Fourier-transform photocurrent
      spectroscopy (FTPS). The statistical copolymer with a lower DPP fraction, when
      blended with a fullerene derivative, shows the signature of an inter charge
      transfer complex state in photocurrent spectroscopy. Furthermore, the absorption
      spectrum of the blended sample with a lower DPP fraction is seen to change as a
      function of an external bias, qualitatively similar to the quantum confined Stark
      effect, from where we estimate the exciton binding energy. The statistical
      copolymer with a higher DPP fraction shows no signal of the inter charge transfer
      states and yields a higher external quantum efficiency in a photovoltaic
      structure. In order to gain insight into the origin of the observed charge
      transfer transitions, we present theoretical studies using density-functional
      theory and time-dependent density-functional theory for the two pristine DPP
      based statistical monomers. 

PMID- 24452362
TI  - Intramolecular excimer formation in hexakis(pyrenyloxy)cyclotriphosphazene:
      photophysical properties, crystal structure, and theoretical investigation.
AB  - A hexakis(pyrenyloxy)cyclotriphosphazene is synthesized by the reaction of
      N3P3Cl6 with 2-hydroxypyrene, and its excimer emission through intramolecular
      interactions in solution and in the solid state has been investigated by
      fluorescence spectroscopy and X-ray crystallography. Thermal and electrochemical
      properties were investigated. A DFT benchmark study has been performed to
      evaluate the intramolecular interactions and molecular orbital levels by
      comparing with the experimental results. 

PMID- 24452361
TI  - Conjugation of vitamin E analog alpha-TOS to Pt(IV) complexes for dual-targeting
      anticancer therapy.
AB  - We report two platinum(IV) complexes conjugated with a vitamin E analog, alpha
      tocopherol succinate (alpha-TOS). One of the conjugates displays the activity of
      both cisplatin and alpha-TOS in cancer cells, causing damage to DNA and
      mitochondria simultaneously. Accordingly, it serves as a promising dual-targeting
      anticancer agent.

PMID- 24452363
TI  - miR-186, miR-3651 and miR-494: potential biomarkers for oral squamous cell
      carcinoma extracted from whole blood.
AB  - microRNAs (miRNAs) are aberrantly expressed in the whole blood of patients
      suffering from different types of cancer. Collection of whole blood samples is a
      minimally invasive procedure. To date, little is known concerning the altered
      miRNA expression in patients suffering from oral squamous cell carcinoma (OSCC).
      The present study aimed to evaluate the difference in miRNA expression in whole
      blood samples in OSCC patients as compared to healthy volunteers who served as
      controls. In 20 blood samples from patients and healthy volunteers, the
      expression patterns of 1,205 human miRNAs were examined by miRNA microarray in
      order to identify those with the most pronounced differential expression. The
      results were verified by quantitative RT-PCR (RT-qPCR) for miR-186, miR-3651 and
      miR-494 using 57 samples of patients and 33 samples of healthy volunteers.
      Receiver operating characteristic (ROC) curves and the highest Youden index were
      calculated in order to assess cut-off points (COPs) that allowed the
      distinguishing of blood samples of OSCC patients from those of healthy
      volunteers. Significantly different expression rates were found for miR-186
      (p=0.01), miR-3651 (p=0.0001) and miR-494 (p=0.004) between the OSCC patients and
      healthy controls. In the OSCC patients, there was a 2-fold upregulation for miR
      494 and miR-3651 and a 2-fold downregulation for miR-186. Based on the determined
      COPs, significant correlations between miR-3651 overexpression and lymph node
      status (p=0.04), tumor grade (p=0.02) and clinical stage (p=0.04) were indicated.
      Aberrant expression levels of miR-186, miR-494 and miR-3651 in whole blood
      samples of OSCC patients may provide the possibility to establish a minimally
      invasive screening method for OSCC.

PMID- 24452364
TI  - [Mentoring program - team approach for career planning].

PMID- 24452359
TI  - Insidious changes in stromal matrix fuel cancer progression.
AB  - Reciprocal interactions between tumor and stromal cells propel cancer progression
      and metastasis. A complete understanding of the complex contributions of the
      tumor stroma to cancer progression necessitates a careful examination of the
      extracellular matrix (ECM), which is largely synthesized and modulated by cancer
      associated fibroblasts. This structurally supportive meshwork serves as a
      signaling scaffold for a myriad of biologic processes and responses favoring
      tumor progression. The ECM is a repository for growth factors and cytokines that
      promote tumor growth, proliferation, and metastasis through diverse interactions
      with soluble and insoluble ECM components. Growth factors activated by proteases
      are involved in the initiation of cell signaling pathways essential to invasion
      and survival. Various transmembrane proteins produced by the cancer stroma bind
      the collagen and fibronectin-rich matrix to induce proliferation, adhesion, and
      migration of cancer cells, as well as protease activation. Integrins are critical
      liaisons between tumor cells and the surrounding stroma, and with their mechano
      sensing ability, induce cell signaling pathways associated with contractility and
      migration. Proteoglycans also bind and interact with various matrix proteins in
      the tumor microenvironment to promote cancer progression. Together, these
      components function to mediate cross-talk between tumor cells and fibroblasts
      ultimately to promote tumor survival and metastasis. These stromal factors, which
      may be expressed differentially according to cancer stage, have prognostic
      utility and potential. This review examines changes in the ECM of cancer
      associated fibroblasts induced through carcinogenesis, and the impact of these
      changes on cancer progression. The implication is that cancer progression, even
      in epithelial cancers, may be based in large part on changes in signaling from
      cancer-associated stromal cells. These changes may provide early prognostic
      indicators to further stratify patients during treatment or alter the timing of
      their follow-up visits and observations.

PMID- 24452365
TI  - Hb Famagusta--analysis of a novel delta-globin chain variant [HBD:c.60C>A] in
      four families with diverse globin genotypes.

PMID- 24452366
TI  - Rituximab single agent in age-related Epstein-Barr virus associated B cell
      disorder complicated by autoimmune anemia and pure red cell aplasia.

PMID- 24452367
TI  - Rates of problematic gambling in a British homeless sample: a preliminary study.
AB  - Homelessness and problem gambling are two public health concerns in the UK that
      are rarely considered concurrently, and little is known about the extent of
      gambling involvement and problematic gambling in the homeless. We recruited 456
      individuals attending homelessness services in London, U.K. All participants
      completed a screen for gambling involvement, and where gambling involvement was
      endorsed, the Problem Gambling Severity Index (PGSI) was administered. The PGSI
      risk categories were compared against data from the 2010 British Gambling
      Prevalence Survey (BGPS). PGSI problem gambling was indicated in 11.6% of the
      homeless population, compared to 0.7% in the BGPS. Of participants endorsing any
      PGSI symptoms, a higher proportion of homeless participants were problem gamblers
      relative to the low and moderate risk groups, compared to the BGPS data. These
      results confirm that the homeless constitute a vulnerable population for problem
      gambling, and that diagnostic tools for gambling involvement should be integrated
      into homelessness services in the U.K.

PMID- 24452369
TI  - Pakikisama: lessons learned in partnership building with Filipinas with breast
      cancer for culturally meaningful support.
AB  - San Francisco Bay Area Filipinas with breast cancer underutilize support
      services. Our partnership engaged in community-based participatory research
      (CBPR) that involved formation of a community advisory board (CAB) representing
      low-income, low-English-proficient Filipinas with breast cancer. While CABs are a
      standard component of CBPR projects, the process of establishing and fostering
      CAB involvement has been under studied. This commentary explores the process our
      team used-building upon the Filipino cultural method of pakikisama which stresses
      making the other feel welcome, safe, and nurtured-to overcome barriers to active
      engagement. Challenges included minimizing power imbalances between the research
      team and CAB, and the establishment of an environment of familiarity, trust and
      caring among CAB members. We recorded all CAB meetings, transcribed them
      verbatim, and Tagalog portions were transcribed into English for analysis.
      Mobilizing pakikisama supported partnership building and allowed CAB members to
      engage in inclusive dialogue and formulate a culturally relevant support model. 

PMID- 24452370
TI  - Primary cutaneous mucinous carcinoma: a systematic review and meta-analysis of
      outcomes after surgery.
AB  - IMPORTANCE: Evidence-based treatment guidelines are not available for primary
      cutaneous mucinous carcinoma (PCMC). OBJECTIVE: To assess outcomes associated
      with surgical treatment of PCMC. DATA SOURCES: MEDLINE, Cumulative Index to
      Nursing and Allied Health, and Embase from 1952 to 2010. Search terms were
      "primary cutaneous mucinous carcinoma," "primary mucinous adenocarcinoma of the
      skin," "primary mucinous sweat-gland carcinoma," and "endocrine mucin-producing
      sweat gland carcinoma." STUDY SELECTION: Articles describing primary data on
      treatment (ie, case reports, case series, and cohort studies) of any patients
      with PCMC. A total of 116 articles were identified, with 90 of these assessed for
      eligibility and 87 used for final analysis. DATA EXTRACTION AND SYNTHESIS: Each
      case was verified to be of primary cutaneous origin by 2 observers.
      Histopathologic descriptions were confirmed to be consistent with PCMC. Extracted
      fields included age, sex, race, lesion duration, tumor diameter, method of
      treatment, follow-up, and whether the lesion recurred or metastasized. MAIN
      OUTCOMES AND MEASURES: Outcomes were dichotomized into good and bad depending on
      the presence of recurrence or metastasis during follow-up. Multivariate logistic
      regression analysis was performed to determine significant factors for predicting
      bad outcomes. RESULTS One hundred fifty-nine cases of PCMC, of whom 54.7% were
      male and 77.2% were white, with mean (SD) age 63.5 (13.2) years, were analyzed.
      Most had been treated with traditional surgical excision (85.5%), with only 9.4%
      of cases treated with Mohs surgery. Older (odds ratio [OR], 0.93; P = .04) and
      Asian (OR, 0.02; P = .01) patients had relatively better postsurgical outcomes.
      Larger tumors (OR, 6.71; P = .14), those persistent for longer prior to surgery
      (OR, 1.02; P = .11), and those located on the trunk (OR, 103.24; P = .005) also
      were associated with poorer outcomes. Limitations included reliance on case
      report data. CONCLUSIONS AND RELEVANCE: Patient demographic characteristics and
      tumor-specific features may provide predictive information regarding the risk of
      postsurgical recurrence and metastasis after treatment of PCMC.

PMID- 24452368
TI  - Off-hour presentation and outcomes in patients with acute myocardial infarction:
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the association between off-hour (weekends and nights)
      presentation, door to balloon times, and mortality in patients with acute
      myocardial infarction. DATA SOURCES: Medline in-process and other non-indexed
      citations, Medline, Embase, Cochrane Database of Systematic Reviews, and Scopus
      through April 2013. STUDY SELECTION: Any study that evaluated the association
      between time of presentation to a healthcare facility and mortality or door to
      balloon times among patients with acute myocardial infarction was included. DATA
      EXTRACTION: Studies' characteristics and outcomes data were extracted. Quality of
      studies was assessed with the Newcastle-Ottawa scale. A random effect meta
      analysis model was applied. Heterogeneity was assessed using the Q statistic and
      I(2). RESULTS: 48 studies with fair quality, enrolling 1,896,859 patients, were
      included in the meta-analysis. 36 studies reported mortality outcomes for
      1,892,424 patients with acute myocardial infarction, and 30 studies reported door
      to balloon times for 70,534 patients with ST elevation myocardial infarction
      (STEMI). Off-hour presentation for patients with acute myocardial infarction was
      associated with higher short term mortality (odds ratio 1.06, 95% confidence
      interval 1.04 to 1.09). Patients with STEMI presenting during off-hours were less
      likely to receive percutaneous coronary intervention within 90 minutes (odds
      ratio 0.40, 0.35 to 0.45) and had longer door to balloon time by 14.8 (95%
      confidence interval 10.7 to 19.0) minutes. A diagnosis of STEMI and countries
      outside North America were associated with larger increase in mortality during
      off-hours. Differences in mortality between off-hours and regular hours have
      increased in recent years. Analyses were associated with statistical
      heterogeneity. CONCLUSION: This systematic review suggests that patients with
      acute myocardial infarction presenting during off-hours have higher mortality,
      and patients with STEMI have longer door to balloon times. Clinical performance
      measures may need to account for differences arising from time of presentation to
      a healthcare facility.

PMID- 24452371
TI  - Diurnal body temperature rise is reduced in diabetes with autonomic neuropathy.
AB  - We conducted a retrospective study of 60 patients with ischemic heart disease (31
      with diabetes and 29 without diabetes) to investigate the impact of diabetes on
      diurnal body temperature patterns. We found that the increase of axillary body
      temperature in the evening was reduced in the presence of diabetes, which was
      associated with autonomic neuropathy.

PMID- 24452372
TI  - The Mindful Way Through the Semester: An Investigation of the Effectiveness of an
      Acceptance-Based Behavioral Therapy Program on Psychological Wellness in First
      Year Students.
AB  - First-year students in higher education deal with an increasing number of mental
      health issues. Cost-effective and time-efficient programs that ease transitions
      and reduce risk of depression are needed. To date, programs informed by both
      cognitive-behavioral and acceptance-based-behavioral therapy (ABBT) approaches
      have produced some positive outcomes, but methodological limitations limit their
      utility. The aim of the present study was to address some of these limitations,
      by developing and preliminary testing the efficacy of a one-session ABBT
      intervention with first-year undergraduates and first-year law students. Ninety
      eight first-year students were randomly assigned to receive either a single
      session 90-min ABBT workshop within their first month of school or to a waitlist
      control condition. Students who received the intervention reported significantly
      less depression and more acceptance. Moreover, increase in acceptance over the
      course of the semester was associated with reductions in depression. Implications
      of these findings for future interventions are discussed. 

PMID- 24452373
TI  - Extracellular membrane vesicles as a mechanism of cell-to-cell communication:
      advantages and disadvantages.
AB  - Microvesicles represent a newly identified mechanism of intercellular
      communication. Two different types of microvesicles have been identified:
      membrane-derived vesicles (EVs) and exosomes. EVs originate by direct budding
      from the plasma membrane, while exosomes arise from ectocytosis of multivesicular
      bodies. Recent attention has focused on the capacity of EVs to alter the
      phenotype of neighboring cells to make them resemble EV-producing cells. Stem
      cells are an abundant source of EVs, and the interaction between stem cells and
      the microenvironment (i.e., stem cell niche) plays a critical role in determining
      stem cell phenotype. The stem cell niche hypothesis predicts that stem cell
      number is limited by the availability of niches releasing the necessary signals
      for self-renewal and survival, and the niche thus provides a mechanism for
      controlling and limiting stem cell numbers. EVs may play a fundamental role in
      this context by transferring genetic information between cells. EVs can transfer
      mRNA and microRNA to target cells, both of which may be involved in the change in
      target-cell phenotype towards that of EV-producing cells. The exchange of genetic
      information may be bidirectional, and EV-mediated transfer of genetic information
      after tissue damage may reprogram stem cells to acquire the phenotypic features
      of the injured tissue cells. In addition, stem cell-derived EVs may induce the de
      differentiation of cells that survive injury by promoting their reentry into the
      cell cycle and subsequently increasing the possibility of tissue regeneration. 

PMID- 24452374
TI  - A-kinase anchoring proteins contribute to loss of E-cadherin and bronchial
      epithelial barrier by cigarette smoke.
AB  - Airway epithelium, which forms the first barrier towards environmental insults,
      is disturbed by cigarette smoking, a major risk factor for developing chronic
      obstructive pulmonary disease (COPD). A-kinase anchoring proteins (AKAP) maintain
      endothelial barrier function and coordinate subcellular localization of protein
      kinase A (PKA). However, the role of AKAPs in epithelial barrier function is
      unknown. We studied the role of AKAPs in regulating human bronchial epithelial
      (Hogg JC, Timens W. Annu Rev Pathol 4: 435-459, 2009; HBE) barrier. Cigarette
      smoke extract (CSE) reduced barrier function in 16HBE cells and the expression of
      the adhesion molecule E-cadherin specifically at the cell membrane. In addition,
      CSE reduced the protein expression of the AKAP family member AKAP9 at the cell
      membrane. The expression of AKAP5 and AKAP12 was unaffected by CSE. AKAP9
      interacted and colocalized with E-cadherin at the cell membrane, suggesting that
      the reduction of both proteins may be related. Interestingly, disruption of AKAP
      PKA interactions by st-Ht31 prevented the CSE-induced reduction of E-cadherin and
      AKAP9 protein expression and subsequent loss of barrier function. Silencing of
      AKAP9 reduced the functional epithelial barrier and prevented the ability of st
      Ht31 to restore membrane localization of E-cadherin. Our data suggest the
      possibility of a specific role for AKAP9 in the maintenance of the epithelial
      barrier. E-cadherin, but not AKAP9, protein expression was reduced in lung tissue
      from COPD patients compared with controls. However, AKAP9 mRNA expression was
      decreased in primary bronchial epithelial cells from current smokers compared
      with non/ex-smokers. In conclusion, our results indicate that AKAP proteins, most
      likely AKAP9, maintain the bronchial epithelial barrier by regulating the E
      cadherin expression at the cell membrane. 

PMID- 24452375
TI  - Tiny transporters: how exosomes and calcineurin signaling regulate miR-23a levels
      during muscle atrophy. Focus on "miR-23a is decreased during muscle atrophy by a
      mechanism that includes calcineurin signaling and exosome-mediated export".

PMID- 24452376
TI  - Elevated cAMP increases aquaporin-3 plasma membrane diffusion.
AB  - Regulated urine concentration takes place in the renal collecting duct upon
      arginine vasopressin (AVP) stimulation, where subapical vesicles containing
      aquaporin-2 (AQP2) are inserted into the apical membrane instantly increasing
      water reabsorption and urine concentration. The reabsorped water exits via
      basolateral AQP3 and AQP4. Upon long-term stimulation with AVP or during thirst,
      expression levels of both AQP2 and AQP3 are increased; however, there is so far
      no evidence for short-term AVP regulation of AQP3 or AQP4. To facilitate the
      increase in transepithelial water transport, AQP3 may be short-term regulated via
      changes in protein-protein interactions, incorporation into lipid rafts, and/or
      changes in steady-state turnover, which could result in changes in the diffusion
      behavior of AQP3. Thus we measured AQP3 diffusion coefficients upon stimulation
      with the AVP mimic forskolin to reveal if AQP3 could be short-term regulated by
      AVP. k-Space image correlation spectroscopy (kICS) analysis of time-lapse image
      sequences of basolateral enhanced green fluorescent protein-tagged AQP3 (AQP3
      EGFP) revealed that the forskolin-mediated elevation of cAMP increased the
      diffusion coefficient by 58% from 0.0147 +/- 0.0082 MUm(2)/s (control) to 0.0232
      +/- 0.0085 MUm(2)/s (forskolin, P < 0.05). Quantum dot-conjugated antibody
      labeling also revealed a significant increase in AQP3 diffusion upon forskolin
      treatment by 44% [0.0104 +/- 0.0040 MUm(2)/s (control) vs. 0.0150 +/- 0.0016
      MUm(2)/s (forskolin, P < 0.05)]. Immunoelectron microscopy showed no obvious
      difference in AQP3-EGFP expression levels or localization in the plasma membrane
      upon forskolin stimulation. Thus AQP3-EGFP diffusion is altered upon increased
      cAMP, which may correspond to basolateral adaptations in response to the
      increased apical water readsorption.

PMID- 24452377
TI  - Force-dependent vinculin binding to talin in live cells: a crucial step in
      anchoring the actin cytoskeleton to focal adhesions.
AB  - Mechanical forces play a pivotal role in the regulation of focal adhesions (FAs)
      where the actin cytoskeleton is anchored to the extracellular matrix through
      integrin and a variety of linker proteins including talin and vinculin. The
      localization of vinculin at FAs depends on mechanical forces. While in vitro
      studies have demonstrated the force-induced increase in vinculin binding to
      talin, it remains unclear whether such a mechanism exists at FAs in vivo. In this
      study, using fibroblasts cultured on elastic silicone substrata, we have examined
      the role of forces in modulating talin-vinculin binding at FAs. Stretching the
      substrata caused vinculin accumulation at talin-containing FAs, and this
      accumulation was abrogated by expressing the talin-binding domain of vinculin
      (domain D1, which inhibits endogenous vinculin from binding to talin). These
      results indicate that mechanical forces loaded to FAs facilitate vinculin binding
      to talin at FAs. In cell-protruding regions, the actin network moved backward
      over talin-containing FAs in domain D1-expressing cells while it was anchored to
      FAs in control cells, suggesting that the force-dependent vinculin binding to
      talin is crucial for anchoring the actin cytoskeleton to FAs in living cells. 

PMID- 24452378
TI  - Effects of low cell pH and elevated inorganic phosphate on the pCa-force
      relationship in single muscle fibers at near-physiological temperatures.
AB  - Intense muscle contraction induces high rates of ATP hydrolysis with resulting
      increases in Pi, H(+), and ADP, factors thought to induce fatigue by interfering
      with steps in the cross-bridge cycle. Force inhibition is less at physiological
      temperatures; thus the role of low pH in fatigue has been questioned. Effects of
      pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were
      assessed in skinned fast and slow rat skeletal muscle fibers at 15 and 30 degrees
      C. At 30 degrees C, pH 6.2 + 30 mM Pi significantly depressed peak force in all
      fiber types, with the greatest effect in type IIx fibers. Across fiber types,
      Ca(2+) sensitivity was depressed by low pH and low pH + high Pi, with the greater
      effect at 30 degrees C. For type IIx fibers at 30 degrees C, half-maximal
      activation (pCa50) was 5.36 at pH 6.2 (no added Pi) and 4.98 at pH 6.2 + 30 mM Pi
      compared with 6.58 in the control condition (pH 7, no added Pi). At 30 degrees C,
      n2, reflective of thick filament cooperativity, was unchanged by low cell pH but
      was depressed from 5.02 to 2.46 in type IIx fibers with pH 6.2 + 30 mM Pi. With
      acidosis, activation thresholds of all fiber types required higher free Ca(2+) at
      15 and 30 degrees C. With the exception of type IIx fibers, the Ca(2+) required
      to reach activation threshold increased further with added Pi. In conclusion, it
      is clear that fatigue-inducing effects of low cell pH and elevated Pi at near
      physiological temperatures are substantial. 

PMID- 24452379
TI  - A new molecular target for blunting organ fibrosis. Focus on "Secreted Frizzled
      related protein 2 as a target in antifibrotic therapeutic intervention".

PMID- 24452380
TI  - Suppression of autophagic genes sensitizes CUG2-overexpressing A549 human lung
      cancer cells to oncolytic vesicular stomatitis virus-induced apoptosis.
AB  - We showed in our previous study that cancer upregulated gene (CUG) 2, a novel
      oncogene, confers resistance to infection of oncolytic vesicular stomatitis virus
      (VSV) by activating Stat1-mediated signal transduction. Since many studies have
      reported that autophagy is involved in virus replication, we investigated whether
      autophagy also plays a role in the antiviral activity in A549 cells
      overexpressing CUG2 (A549-CUG2). We suppressed Atg5 or Beclin 1 expression using
      siRNA and examined its effect on the susceptibility of cells to infection by
      oncolytic VSV. We found that A549-CUG2 cells treated with Atg5 or Beclin 1 siRNA
      became susceptible to VSV infection, whereas A549-CUG2 cells treated with control
      siRNA were resistant. This result suggests that autophagy is involved in the
      antiviral response of A549-CUG2 cells. Further investigation revealed that
      autophagy impairment enhanced the generation of reactive oxygen species (ROS),
      which resulted in inactivation of S6 kinase. Under these conditions, the levels
      of ISG15 transcript and protein decreased, which conferred on A549-CUG2 cell
      susceptibility to VSV infection. Finally, we found that overloading of H2O2
      sensitized control A549-CUG2 cells to VSV-induced apoptosis. Taken together,
      these results indicate that autophagy impairment induces excessive ROS formation,
      which decreases S6 kinase activity and ISG15 expression, ultimately rendering the
      A549-CUG2 cells susceptible to VSV infection. We propose that autophagy
      impairment is a potential strategy for successful VSV virotherapy of CUG2
      overexpressing tumors.

PMID- 24452381
TI  - Calcifying fibrous tumor of the small intestine associated with Castleman-like
      lymphadenopathy.
AB  - Calcifying fibrous tumor is a rare mesenchymal tumor that most commonly presents
      in younger individuals. We report the case of a 25-year-old woman that presented
      with severe abdominal pain and a small bowel mass at the site of an ileocolic
      intussusception with associated mesenteric lymphadenopathy. Surgical resection
      was performed, and pathologic analysis revealed that the mass was a calcifying
      fibrous tumor associated with Castleman-like adenopathy. This case intends to
      support a possible association between these two entities. 

PMID- 24452382
TI  - Does stimulus complexity determine whether working memory storage relies on
      prefrontal or sensory cortex?
AB  - Traditionally, working and short-term memory (WM/STM) have been believed to rely
      on storage systems located in prefrontal cortex (PFC). However, recent
      experimental and theoretical efforts have suggested that, in many cases, sensory
      or other task-relevant cortex is the actual storage substrate for WM/STM. What
      factors determine whether a given WM/STM task relies on PFC or sensory cortex? In
      the present article, we outline recent experimental findings and suggest that the
      dimensionality or complexity of the to-be-remembered property or properties of a
      stimulus can be a determining factor. 

PMID- 24452383
TI  - Orienting attention in visual working memory requires central capacity: decreased
      retro-cue effects under dual-task conditions.
AB  - The retro-cue effect (RCE) describes superior working memory performance for
      validly cued stimulus locations long after encoding has ended. Importantly, this
      happens with delays beyond the range of iconic memory. In general, the RCE is a
      stable phenomenon that emerges under varied stimulus configurations and timing
      parameters. We investigated its susceptibility to dual-task interference to
      determine the attentional requirements at the time point of cue onset and
      encoding. In Experiment 1, we compared single- with dual-task conditions. In
      Experiment 2, we borrowed from the psychological refractory period paradigm and
      compared conditions with high and low (dual-) task overlap. The secondary task
      was always binary tone discrimination requiring a manual response. Across both
      experiments, an RCE was found, but it was diminished in magnitude in the critical
      dual-task conditions. A previous study did not find evidence that sustained
      attention is required in the interval between cue offset and test. Our results
      apparently contradict these findings and point to a critical time period around
      cue onset and briefly thereafter during which attention is required. 

PMID- 24452384
TI  - Evidence for scene-based motion correspondence.
AB  - To maintain stable object representations as our eyes or the objects themselves
      move, the visual system must determine how newly sampled information relates to
      existing object representations. To solve this correspondence problem, the visual
      system uses not only spatiotemporal information (e.g., the spatial and temporal
      proximity between elements), but also feature information (e.g., the similarity
      in size or luminance between elements). Here we asked whether motion
      correspondence relies solely on image-based feature information, or whether it is
      influenced by scene-based information (e.g., the perceived sizes of surfaces or
      the perceived illumination conditions). We manipulated scene-based information
      separately from image-based information in the Ternus display, an ambiguous
      apparent-motion display, and found that scene-based information influences how
      motion correspondence is resolved, indicating that theories of motion
      correspondence that are based on "scene-blind" mechanisms are insufficient. 

PMID- 24452385
TI  - The effect of the weather on pulmonary exacerbations and viral infections among
      adults with cystic fibrosis.
AB  - The effect of changes in the weather on the respiratory health of patients with
      cystic fibrosis (CF) is unclear. We conducted a prospective study to determine
      the impact of climate and season on the incidence of viral respiratory infections
      (VRI) and pulmonary exacerbations (PEx) among adults with CF. Between December
      2010 and April 2012, 98 adults with CF were followed for 12 months. Polymerase
      chain reaction assays for nine viruses were performed on sputum, nose and throat
      swabs every 2 months and additionally at onset of PEx. Hourly temperature and
      relative humidity measurements were recorded throughout the study. Statistical
      analysis utilized generalized estimating equation (GEE) models. Pre-specified
      criteria for VRI and PEx were met at 29% and 37% of visits, respectively.
      Rhinovirus accounted for 72% of identified viruses. Incidence of rhinovirus
      peaked in autumn while non-rhinovirus VRI peaked in winter. Rhinovirus was
      associated with increased mean temperatures (OR 1.07; p = 0.001), while non
      rhinovirus VRI was associated with lower mean temperatures (OR 0.87; p < 0.001).
      PEx occurred frequently throughout the study with no clear seasonal pattern
      observed. There was no significant association between climate variables and the
      incidence of either PEx or antibiotic prescription. There is a seasonal pattern
      to VRI in adults with CF. The incidence of VRI but not PEx is associated with
      changes in ambient temperature.

PMID- 24452386
TI  - Chilling and heat requirements for leaf unfolding in European beech and sessile
      oak populations at the southern limit of their distribution range.
AB  - With global warming, an advance in spring leaf phenology has been reported
      worldwide. However, it is difficult to forecast phenology for a given species,
      due to a lack of knowledge about chilling requirements. We quantified chilling
      and heat requirements for leaf unfolding in two European tree species and
      investigated their relative contributions to phenological variations between and
      within populations. We used an extensive database containing information about
      the leaf phenology of 14 oak and 10 beech populations monitored over elevation
      gradients since 2005. In parallel, we studied the various bud dormancy phases, in
      controlled conditions, by regularly sampling low- and high-elevation populations
      during fall and winter. Oak was 2.3 times more sensitive to temperature for leaf
      unfolding over the elevation gradient and had a lower chilling requirement for
      dormancy release than beech. We found that chilling is currently insufficient for
      the full release of dormancy, for both species, at the lowest elevations in the
      area studied. Genetic variation in leaf unfolding timing between and within oak
      populations was probably due to differences in heat requirement rather than
      differences in chilling requirement. Our results demonstrate the importance of
      chilling for leaf unfolding in forest trees and indicate that the advance in leaf
      unfolding phenology with increasing temperature will probably be less pronounced
      than forecasted. This highlights the urgent need to determine experimentally the
      interactions between chilling and heat requirements in forest tree species, to
      improve our understanding and modeling of changes in phenological timing under
      global warming. 

PMID- 24452388
TI  - Chromothripsis: how does such a catastrophic event impact human reproduction?
AB  - The recent discovery of a new kind of massive chromosomal rearrangement, baptized
      chromothripsis (chromo for chromosomes, thripsis for shattering into pieces),
      greatly modifies our understanding of molecular mechanisms implicated in the
      repair of DNA damage and the genesis of complex chromosomal rearrangements.
      Initially described in cancers, and then in constitutional rearrangements,
      chromothripsis is characterized by the shattering of one (or a few) chromosome(s)
      segments followed by a chaotic reassembly of the chromosomal fragments, occurring
      during one unique cellular event. The diversity and the high complexity of
      chromothripsis events raise questions about their origin, their ties to
      chromosome instability and their impact in pathology. Several causative
      mechanisms, involving abortive apoptosis, telomere erosion, mitotic errors,
      micronuclei formation and p53 inactivation, have been proposed. The remarkable
      point is that all these mechanisms have been identified in the field of human
      reproduction as causal factors for reproductive failures and chromosomal
      abnormalities. Consequently, it seems important to consider this unexpected
      catastrophic phenomenon in the context of fertilization and early embryonic
      development in order to discuss its potential impact on human reproduction. 

PMID- 24452389
TI  - A combined theoretical and experimental study for silver electroplating.
AB  - A novel method combined theoretical and experimental study for environmental
      friendly silver electroplating was introduced. Quantum chemical calculations and
      molecular dynamic (MD) simulations were employed for predicting the behaviour and
      function of the complexing agents. Electronic properties, orbital information,
      and single point energies of the 5,5-dimethylhydantoin (DMH), nicotinic acid
      (NA), as well as their silver(I)-complexes were provided by quantum chemical
      calculations based on density functional theory (DFT). Adsorption behaviors of
      the agents on copper and silver surfaces were investigated using MD simulations.
      Basing on the data of quantum chemical calculations and MD simulations, we
      believed that DMH and NA could be the promising complexing agents for silver
      electroplating. The experimental results, including of electrochemical
      measurement and silver electroplating, further confirmed the above prediction.
      This efficient and versatile method thus opens a new window to study or design
      complexing agents for generalized metal electroplating and will vigorously
      promote the level of this research region. 

PMID- 24452390
TI  - Minimal residual disease monitoring: the new standard for treatment evaluation of
      haematological malignancies?
AB  - Minimal residual disease (MRD) refers to the small number of malignant cells that
      remain after therapy when the patient is in remission and shows no symptoms or
      overt signs of disease. Current treatment protocols for haematological
      malignancies allow most patients to obtain some form of MRD state, but cure
      seldom follows and in most cases fatal relapses occur sooner or later, leaving a
      bitter impression of having won a battle yet lost the war. MRD detection and
      quantification are used for evaluation of treatment efficiency, patient risk
      stratification and long-term outcome prediction. Whereas multicolour flow
      cytometry (MCFC) and polymerase chain reaction (PCR) based methods constitute the
      two most commonly used techniques for MRD detection, next generation sequencing
      will certainly be widely employed in the future. As MRD reflects the nature of
      the malignant disease itself, including its sensitivity to the drug regimens
      applied, it constitutes the ideal method for surveillance and patient follow-up.
      The morphological examination of peripheral blood or bone marrow smears, although
      still an indispensable part of routine laboratory testing, is clearly
      insufficient for patient management, and clinicians should not ask themselves
      whether to look for MRD or not, but how and when. 

PMID- 24452387
TI  - The potential role of rho GTPases in Alzheimer's disease pathogenesis.
AB  - Alzheimer's disease (AD) is characterized by a wide loss of synapses and
      dendritic spines. Despite extensive efforts, the molecular mechanisms driving
      this detrimental alteration have not yet been determined. Among the factors
      potentially mediating this loss of neuronal connectivity, the contribution of Rho
      GTPases is of particular interest. This family of proteins is classically
      considered a key regulator of actin cytoskeleton remodeling and dendritic spine
      maintenance, but new insights into the complex dynamics of its regulation have
      recently determined how its signaling cascade is still largely unknown, both in
      physiological and pathological conditions. Here, we review the growing evidence
      supporting the potential involvement of Rho GTPases in spine loss, which is a
      unanimously recognized hallmark of early AD pathogenesis. We also discuss some
      new insights into Rho GTPase signaling framework that might explain several
      controversial results that have been published. The study of the connection
      between AD and Rho GTPases represents a quite unchartered avenue that holds
      therapeutic potential. 

PMID- 24452391
TI  - Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of
      glutamate transporter EAAT2.
AB  - Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe
      alcohol dependence that presents a significant challenge to treatment. Although
      AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines,
      which target the GABAergic system, comprise the first line of treatment for AWS.
      Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a beta
      lactam antibiotic known to increase the expression and activity of glutamate
      uptake transporter EAAT2, reduces the occurrence or severity of ethanol
      withdrawal manifestations. After a 2-week period of habituation to ethanol in two
      bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg)
      every 6 h for 3-5 consecutive days via gavage. Rats were then deprived of ethanol
      for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or
      saline twice a day starting 12 h after the last ethanol administration.
      Withdrawal manifestations were captured by continuous video recording and coded.
      The evolution of ethanol withdrawal was markedly different for P rats vs Wistar
      rats, with withdrawal manifestations occurring >12 h later in P rats than in
      Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day)
      reduced or abolished all manifestations of ethanol withdrawal in both rat
      variants and prevented withdrawal-induced escalation of alcohol intake. Finally,
      ceftriaxone treatment was associated with lasting upregulation of ethanol
      withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the
      role of ceftriaxone in alleviating alcohol withdrawal and open a novel
      pharmacologic avenue that requires clinical evaluation in patients with AWS.

PMID- 24452393
TI  - First-in-human, phase I dose-escalation study of single and multiple doses of a
      first-in-class enhancer of fluoropyrimidines, a dUTPase inhibitor (TAS-114) in
      healthy male volunteers.
AB  - PURPOSE: TAS-114 is a first-in-class oral deoxyuridine triphosphatase (dUTPase)
      inhibitor, which acts as a modulator of the pyrimidine nucleotide metabolic
      pathway. This was a first-in-human, phase 1 study that investigated the
      pharmacokinetics (PK) and safety of single-agent TAS-114 when it was given at
      single and multiple doses. METHODS: For the single-dose cohort (n = 25), healthy
      male volunteers received a single dose of TAS-114 at 6, 18, 60, 150, and 300 mg.
      The magnitude of dihydropyrimidine dehydrogenase (DPD) inhibition and the food
      effect on TAS-114 PK were also investigated. For the multiple-dose cohort (n =
      10), subjects received TAS-114 for 14 days consecutively. RESULTS: In the dose
      escalating single-dose cohort, the disposition of TAS-114 followed linear
      kinetics. The elimination half-life was approximately 2 h. The urine excretion
      rate and food effect were minimal. A significant increase in uracil Cmax was
      observed at administered doses of 150 mg or higher of TAS-114, suggesting that
      significant inhibition of DPD occurred at these doses. No apparent CYP3A4 auto
      induction was observed in the multiple-dose cohort. No significant safety
      concerns at these dose levels were noted after single and multiple dosing.
      CONCLUSIONS: TAS-114 has shown both a favorable safety and pharmacokinetic
      profile after single and repeated doses. TAS-114 was considered to possess a
      moderate DPD inhibitory effect. These findings will facilitate clinical studies
      of the combination chemotherapies in cancer patients and may reduce the safety
      risk in the frail cancer patients.

PMID- 24452392
TI  - A novel somatic FGFR3 mutation in primary lung cancer.
AB  - The recent discovery of mutations and fusions of oncokinase genes in a subset of
      lung cancers (LCs) is of considerable clinical interest, since LCs containing
      such mutations or fusion transcripts are reportedly sensitive to kinase
      inhibitors. To better understand the role of the recently identified fibroblast
      growth factor receptor 3 (FGFR3) mutations and fusions in pulmonary
      carcinogenesis, we examined 214 LCs for mutations in the mutation cluster region
      of the FGFR3 gene using sequencing analysis. We also examined 190 LCs for the
      FGFR3-TACC3 and FGFR3-BAIAP2L1 fusion transcripts using reverse transcription
      polymerase chain reaction (RT-PCR) analysis. Although the expression of FGFR3
      TACC3 and FGFR3-BAIAP2L1 fusion transcripts was not detected in any of the
      carcinomas, somatic FGFR3 mutations were detected in two (0.9%) LCs. The two
      mutations were the same, i.e., p.R248H. That was a novel mutation occurring in
      the same codon as p.R248C, for which an oncogenic potential has previously been
      shown. Increased FGFR3 expression was shown in the two LCs containing the FGFR3
      p.R248H mutation using qPCR. Histologically, both carcinomas were squamous cell
      carcinomas, therefore the incidence of the FGFR3 mutation among the squamous cell
      carcinoma cases was calculated as 3.2% (2/63). When we examined other co
      occurring genetic abnormalities, one case exhibited a p53 p.R273C mutation, while
      the other case exhibited PIK3CA and SOX2 amplifications. The above results
      suggest that an FGFR3 p.R248H mutation is involved in the carcinogenesis of a
      subset of LCs and may contribute to the elucidation of the characteristics of
      FGFR3 mutation-positive LCs in the future.

PMID- 24452394
TI  - High-dose vitamin B1 reduces proliferation in cancer cell lines analogous to
      dichloroacetate.
AB  - PURPOSE: The dichotomous effect of thiamine supplementation on cancer cell growth
      is characterized by growth stimulation at low doses and growth suppression at
      high doses. Unfortunately, how thiamine reduces cancer cell proliferation is
      currently unknown. Recent focuses on metabolic targets for cancer therapy have
      exploited the altered regulation of the thiamine-dependent enzyme pyruvate
      dehydrogenase (PDH). Cancer cells inactivate PDH through phosphorylation by
      overexpression of pyruvate dehydrogenase kinases (PDKs). Inhibition of PDKs by
      dichloracetate (DCA) exhibits a growth suppressive effect in many cancers.
      Recently, it has been shown that the thiamine coenzyme, thiamine pyrophosphate
      reduces PDK-mediated phosphorylation of PDH. Therefore, the objective of this
      study was to determine whether high-dose thiamine supplementation reduces cell
      proliferation through a DCA-like mechanism. METHODS: Cytotoxicity of thiamine and
      DCA was assessed in SK-N-BE and Panc-1 cancer cell lines. Comparative effects of
      high-dose thiamine and DCA on PDH phosphorylation were measured by Western blot.
      The metabolic impact of PDH reactivation was determined by glucose and lactate
      assays. Changes in the mitochondrial membrane potential, reactive oxygen species
      (ROS) production, and caspase-3 activation were assessed to characterize the
      mechanism of action. RESULTS: Thiamine exhibited a lower IC50 value in both cell
      lines compared with DCA. Both thiamine and DCA reduced the extent of PDH
      phosphorylation, reduced glucose consumption, lactate production, and
      mitochondrial membrane potential. High-dose thiamine and DCA did not increase
      ROS, but increased caspase-3 activity. CONCLUSION: Our findings suggest that high
      dose thiamine reduces cancer cell proliferation by a mechanism similar to that
      described for dichloroacetate.

PMID- 24452395
TI  - A phase I study of olaratumab, an anti-platelet-derived growth factor receptor
      alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors.
AB  - PURPOSE: The platelet-derived growth factor receptor (PDGFR) has an important
      role in tumorigenesis and tumor progression. Olaratumab (IMC-3G3) is a fully
      human monoclonal antibody that selectively binds human PDGFRalpha and blocks
      ligand binding. This phase I study assessed the safety, maximum tolerated dose
      (MTD), recommended phase II dose (RP2D), pharmacokinetics, and preliminary
      antitumor activity of olaratumab in patients with advanced solid tumors. METHODS:
      Patients were enrolled into five dose-escalating cohorts of 3-6 patients each.
      Olaratumab was administered intravenously weekly at 4, 8, or 16 mg/kg (cohorts 1
      3) or once every other week at 15 or 20 mg/kg (cohorts 4-5), with 4 weeks/cycle.
      RESULTS: Nineteen patients were treated in five cohorts. There were no dose
      limiting toxicities; the MTD was not identified with the doses studied. The most
      common olaratumab-related adverse events (AE) were fatigue and infusion reactions
      (10.5 % each). With the exception of 1 patient (20 mg/kg) experiencing two grade
      3 drug-related AEs after the dose-limiting toxicity assessment period, all drug
      related AEs were grade 1 or 2. The trough concentrations (C min) for 16 mg/kg
      weekly and 20 mg/kg biweekly were higher than 155 MUg/mL, and the concentration
      found to be efficacious in preclinical xenograft models. Twelve patients (63.2 %)
      had a best response of stable disease [median duration of 3.9 months (95 % CI 2.3
      8.7)]. CONCLUSIONS: Olaratumab was well tolerated and showed preliminary
      antitumor activity. RP2Ds are 16 mg/kg weekly and 20 mg/kg biweekly. Phase II
      studies of olaratumab as monotherapy and in combination are ongoing in several
      tumor types.

PMID- 24452396
TI  - Pyridine imines as ligands in luminescent iridium complexes.
AB  - Biscyclometallated iridium complexes [Ir(ppz)2(X^Y)][PF6] (X^Y = pyridine imine)
      have been synthesised. The pyridineimine ligands are prepared in situ during the
      complexation. The complexes show room temperature emission between 640 and 780 nm
      in CH2Cl2 solution. The emission is red shifted compared with the analogous
      bipyridine complex [Ir(ppz)2(bipy)][PF6]. DFT calculations have been used to shed
      light on the influence of the imine substituent on the electrochemical and
      photochemical properties. In particular, the calculations suggests that there is
      a significant change in geometry between the ground state and the first triplet
      excited state for arylimines but not for alkylimines, leading to much weaker
      emission for the arylimine complexes. The work demonstrates that pyridineimines
      can be used as a substitute for bipyridines in luminescent iridium complexes. 

PMID- 24452397
TI  - Polaron coupling in graphene field effect transistors on patterned self-assembled
      monolayer.
AB  - We investigated the device characteristics of a graphene field effect transistor
      (FET) of which interfaces were controlled by a self-assembled monolayer (SAM).
      Electrical transport measurements together with Raman spectroscopy
      characterizations for bilayer graphene (BLG) and single layer graphene (SLG) on
      micro-patterned SAM (mp-SAM), respectively, elucidate spatial carrier modulations
      on the graphene sheets driven by mp-SAM. The SLG-mp-SAM-FET device exhibits
      unconventional graphene p-n junction characteristics depending on the polarity of
      source-drain voltage. The observed characteristics can be interpreted as a
      velocity saturation of hole carriers coupled with polaron states, of which phonon
      energy is around 30 meV, on the SAM molecules at the graphene p-n junction. The
      SAM-based micro fabrication techniques presented in this report not only provide
      a spatial control of electronic properties for graphene but also lend a new
      perspective in the understanding of graphene-substrate interface based molecular
      self-assembled systems. 

PMID- 24452398
TI  - Rational hopping of a peptidic scaffold into non-peptidic scaffolds: structurally
      novel potent proteasome inhibitors derived from a natural product, belactosin A.
AB  - Rational scaffold hopping of a natural product belactosin A derivative was
      successfully achieved based on the pharmacophore model constructed. The peptidic
      scaffold was replaced by significantly simplified non-peptidic scaffolds, by
      which weak belactosin A (IC50 = 1440 nM) was converted into highly potent non
      peptidic inhibitors (IC50 = 26-393 nM). 

PMID- 24452399
TI  - [Costs and benefits of quality management].
AB  - The establishment of quality management (QM) has been mandatory for health care
      providers of the national health insurance since 2004; however, certification is
      so far only compulsory for rehabilitation clinics. The costs have so far only
      been quantified in a few medical studies, while they are widely known in business
      administration with a basic distinction made between planning, steering,
      auditing, and declaration costs. Another business economics approach
      differentiates between prevention, appraisal, and non-conformance costs. The
      benefits of QM relates to customers, employees, external service providers, and
      health insurance providers. Also important in our consideration of the patient as
      a customer is that they should not be considered a customer in the usual business
      sense because the patient is in an emergency situation and can not freely decide.
      Improvements in treatment quality and in reducing the rate of adverse events make
      up the largest portion of the benefits of QM. Furthermore, QM can have a positive
      influence on motivation and employee recruitment. In addition, the cost savings
      that result despite costs for QM must not be forgotten.

PMID- 24452400
TI  - [Economic implications of bedside communication errors].
AB  - Good communication can contribute significantly to avoiding expert disputes. An
      open and honest relationship in dealing with errors allows people to learn from
      them and avoid them in the future. This benefits both doctors and patients. 

PMID- 24452401
TI  - [Development of the 2014 G-DRG system. Departure from coding of secondary
      diagnoses?].
AB  - The objective of the German DRG (diagnosis-related groups) system is to
      adequately reimburse hospital costs using flat rate payments. The goal is to
      thereby achieve the most adequate representation of hospital costs in flat rate
      payments. The DRG for 2014 is based on the actual number of cases treated and the
      costs determined from 2012. For 2014, the current changes of the DRG system for
      the specialty urology concerning the coding and recording of secondary diagnoses
      are presented and discussed. 

PMID- 24452402
TI  - [How can the coding quality in the DRG system be determined?].
AB  - The permanent adjustments since 2003 to the G-DRG system have made the system
      even less understandable, so that many users have the feeling of feeding data
      into a black box which gives them a result without them being able to actively
      use the system itself. While chief physicians, senior physicians, and nursing
      managers are responsible to management for the results of the billing, they are
      in most cases not involved in the steps of DRG coding and billing. From this
      situation, a common question arises: "How well does my department code?" This
      uncertainty is exploited by many commercial vendors, who offer a wide variety of
      approaches for DRG optimization. The goal of this work is to provide advice as to
      how coding quality can be determined. 

PMID- 24452403
TI  - [German-Japanese scientific exchange in urology in the early 20th century].
AB  - This paper analyzes the importance of the German language and German culture and
      institutional development of urology in Japan in the early 20th century, starting
      from the development of the medical school for Japanese in Germany and their
      function in the process of modernization of the Meiji period (1868-1912).
      Examples of bi-directional German-Japanese relations in medicine, which also
      included an integrated knowledge transfer, are shown. The study is based mainly
      on Japanese and German sources about Japanese physicians in Germany as well as
      contemporary publications in German and international medical journals.
      Methodologically, the article combines quantitative analysis with individual
      biographical aspects. 

PMID- 24452404
TI  - ["UroEvidence" - Centre for knowledge translation of the DGU (German Society of
      Urology). Summarizing, analysing and making current knowledge available].

PMID- 24452406
TI  - Frequency and predictors of non-compliance to dietary recommendations among
      hypertensive patients.
AB  - Compliance to dietary recommendations among hypertensive people is a major health
      care issue. Non-compliance can nullify the effects of even the most scientific
      and optimum treatment plan. The main aim of this study was to determine the
      frequency and predictors of non-adherence in our region. We also investigated the
      possible factors based on patient opinions that could increase compliance. A
      sample of 400 adult patients, diagnosed with hypertension for at least 3 years,
      who visited Civil Hospital during the time period April-June 2013 were included
      in this cross sectional study. Patient data and opinions were collected by two
      trained interviewers using a pre-coded questionnaire. Compliance was assessed
      based on patients self report. More than three quarters (n = 310, 77.5%) of the
      hypertensive patients were non-compliant. More than one social gathering in a
      week, peer-influence, no friends to follow the recommended diet plan and lack of
      believe regarding diet as an effective measure to control blood pressure were
      found to be the significant predictors of non-compliance (P values <0.0001).
      Counseling was thought to be the most effective way by the patients to increase
      adherence. Non-compliance to dietary recommendations is a major problem prevalent
      especially in Pakistan. There is an urgent need for doctors and nurses to counsel
      their patients effectively to prevent future morbidities and mortalities because
      of non-compliance.

PMID- 24452407
TI  - Acute myocardial infarction.

PMID- 24452408
TI  - The modified Glasgow prognostic score as a predictor of survival after
      hepatectomy for colorectal liver metastases.
AB  - BACKGROUND: The inflammation-based Glasgow prognostic score (GPS) has been
      demonstrated to be prognostic for various tumors. We investigated the value of
      the modified GPS (mGPS) for the prognosis of patients undergoing curative
      resection for colorectal liver metastases (CRLM). METHODS: A total of 343
      patients were enrolled onto this study. The mGPS was calculated as follows: mGPS
      0, C-reactive protein (CRP) <=10 mg/L; mGPS-1, CRP >10 mg/L and albumin >=35 g/L;
      and mGPS-2, CRP >10 mg/L and albumin <35 g/L. Prognostic significance was
      retrospectively analyzed by univariate and multivariate analyses. RESULTS: Of the
      343 patients, 295 (86.0 %) were assigned to mGPS-0, 33 (9.6 %) to mGPS-1, and 15
      (4.4 %) to mGPS-2. The median disease-free survival of patients with mGPS-0, -1,
      and -2 was 18.3, 15.5, and 5.2 months, respectively. The median cancer-specific
      survival (CSS) of patients with mGPS-0, -1, and -2 was 89.5, 62.2, and 25.8
      months, respectively. The CSS of patients with mGPS-0 was significantly longer
      than that of patients with mGPS-2. Multivariate analysis revealed a significant
      association between cancer-related postoperative mortality and mGPS and
      carcinoembryonic antigen level. CONCLUSIONS: The preoperative mGPS is a useful
      prognostic factor for postoperative survival in patients undergoing curative
      resection for CRLM.

PMID- 24452409
TI  - Operative failure in minimally invasive parathyroidectomy utilizing an
      intraoperative parathyroid hormone assay.
AB  - BACKGROUND: Minimally invasive parathyroidectomy (MIP) is a targeted operation to
      cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone
      monitoring (IOPTH). The purpose of this study was to quantify the operative
      failure of MIP. METHODS: Utilizing institutional parathyroid surgery database,
      demographic, operative, and biochemical data were analyzed for successful and
      failed MIP. Operative failure was defined as <6 months of eucalcemia after
      operation. RESULTS: Five hundred thirty-eight patients (96.6 %) had successful
      MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The
      major cause of operative failure (11 of 19) was the result of surgeons' inability
      to identify all abnormal parathyroid glands. The remaining eight operative
      failures were the result of falsely positive IOPTH results. Eleven of 19 patients
      whose MIP had failed underwent a second parathyroid surgery. All but one of these
      patients achieved operative success, and 9 patients had missed multigland
      disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical
      exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease,
      and all had successful operations. Patients with a marginal IOPTH decrease (50-59
      %) had a treatment failure rate of 20 %. CONCLUSIONS: The most common cause of
      operative failure in MIP utilizing IOPTH was the result of surgeons' failure to
      identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a
      targeted MIP utilizing IOPTH can achieve an excellent operative success rate
      without routine BCE. Selective BCE on patients with marginal IOPTH decrease may
      improve surgical outcome.

PMID- 24452410
TI  - Invited commentary on "Thoraco-pleuro-pneumonectomy (TPP) with riblike
      reconstruction for recurrent thoracic sarcomas" by A. Gronchi et al., (ASO-2013
      09-1533.R1).

PMID- 24452411
TI  - Neoadjuvant chemotherapy for localized pancreatic cancer: too little or too long?

PMID- 24452413
TI  - Lessons learned? Nurses and health demonstration projects in New York City, 1920
      1935.
AB  - This historical case study looks at two foundation-funded health demonstration
      projects in New York City from 1920 to 1935. It specifically examines the
      disciplinary interests, the work, and the aspirations of nurses and social
      workers as they tried to provide coordinated and cost-effective care to the
      individuals and families with whom they worked. It attends to the processes--not
      just the outcomes--involved in the coming together and moving apart of the
      different organizations, disciplinary interests, knowledge domains, and spheres
      of public and private responsibilities involved in caring for those in need. It
      locates the problems of coordination within disciplinary tensions as nurses and
      social worker--working within a web of gender, class, race, and power--sought to
      advance their own disciplinary interests even as they searched for better ways to
      care for the families in their charge.

PMID- 24452412
TI  - Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced
      peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal
      cancer patients.
AB  - BACKGROUND: The oxaliplatin-based regimen FOLFOX is widely used to treat patients
      with advanced colorectal cancer (CRC). However, dose-limiting toxicity after
      continuous oxaliplatin administration can lead to peripheral neuropathy. Several
      agents, including opioids, that have been employed to treat oxaliplatin-induced
      peripheral neuropathy (OIPN) have been examined in clinical settings regarding
      their protective and therapeutic effects. However, the pharmacotherapy of these
      agents has not yet been established. Therefore, we investigated the efficacy and
      tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC
      patients. METHODS: This was a single-center retrospective study of 64 CRC
      patients who underwent FOLFOX therapy at the Toho University Sakura Medical
      Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly
      administered to 29 patients (OXY group), whereas the additional 35 patients (non
      OXY group) were not given oxycodone during the FOLFOX treatment course. The
      incidence and severity of OIPN and the number of FOLFOX cycles were measured and
      compared between the two groups. Neurological toxicities were assessed according
      to the Common Terminology Criteria for Advanced Events, version 3.0. RESULTS: All
      study patients had OIPN. Most patients experienced grade 1 or 2 sensory
      neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non
      OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy,
      whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due
      to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY
      and non-OXY groups were 13 (range, 6-46) and 7 (range, 2-18), respectively (P <
      0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m(2) (range, 408.7
      3385.3 mg/m(2)) in the OXY group and 483.0 mg/m(2) (range 76.2-1414.1 mg/m(2)) in
      the non-OXY group (P < 0.05). CONCLUSIONS: Our findings indicate that CR
      oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX
      therapy.

PMID- 24452414
TI  - Cooperative breeding and Aka children's nutritional status: is flexibility key?
AB  - Research suggests that nonmaternal caregivers (allomothers) offer essential
      assistance through caregiving and provisioning, helping to support lengthy child
      development. Here, we examine the role of allomothers and the broader social and
      sharing network on Aka forager children's anthropometrics. We hypothesize that
      nonmaternal investors strategically target their assistance when it is most
      needed and when it will have the greatest effect. We evaluate children's
      nutritional status using WHO standards [weight-for-age (WAZ), height-for-age
      (HAZ), and weight-for-height (WHZ)] during four periods of child development
      [early infancy (birth to <9 months), mobility to weaning (9 to <36 months), early
      childhood (36 to <72 months), and middle childhood (72 to <120 months); N = 127].
      We explore the effects of allomothers and the social network across these
      different risk periods and examine whether the broader social network buffers the
      loss of a primary allomother. ANOVA results suggest that girls may be
      experiencing some growth faltering, while boys start smaller and remain small
      across these stages. We used OLS multiple regression models to evaluate the
      effects of sex, camp composition, risk periods, and allomothers' presence on WAZ,
      HAZ, and WHZ. Grandmothers are the most influential allomother, with their effect
      most evident during the 9 to <36 month period. Camp size was also associated with
      greater WAZ, suggesting that children residing in small camps may be
      disadvantaged. Our findings also indicate that, under specific residence
      patterns, cooperative child rearing networks buffer the loss of a grandmother.
      Overall, our results suggest the importance of social networks to children's
      nutritional status and that individuals target investment to critical phases.

PMID- 24452415
TI  - Characterization of cleavage intermediate and star sites of RM.Tth111II.
AB  - Tth111II is a thermostable Type IIGS restriction enzyme that recognizes DNA sites
      CAARCA (R = A or G) and cleaves downstream at N11/N9. Here, the tth111IIRM gene
      was cloned and expressed in E. coli, and Tth111II was purified. The purified
      enzyme contains internally-bound S-adenosylmethionine (SAM). When the internal
      SAM was removed, the endonuclease activity was stimulated by adding SAM or its
      analog sinefungin. The cleavage intermediate is mostly top-strand nicked DNA on a
      single-site plasmid. Addition of duplex oligos with a cognate site stimulates
      cleavage activity of the one-site substrate. Tth111II cleaves a two-site plasmid
      DNA with equal efficiency regardless of site orientation. We propose the top
      strand nicking is carried out by a Tth111II monomer and bottom-strand cleavage is
      carried out by a transient dimer. Tth111II methylates cleavage product-like
      duplex oligos CAAACAN9, but the modification rate is estimated to be much slower
      than the top-strand nicking rate. We cloned and sequenced a number of Tth111II
      star sites which are 1-bp different from the cognate sites. A biochemical pathway
      is proposed for the restriction and methylation activities of Tth111II. 

PMID- 24452416
TI  - miR-222 regulates the cell biological behavior of oral squamous cell carcinoma by
      targeting PUMA.
AB  - Previous reports have shown that low expression of p53 upregulated modulator of
      apoptosis (PUMA) and abnormal expression patterns of a number of miRNAs may be
      associated with poor prognosis in various types of human malignancies. As a
      member of the oncomiRs, miR-222 has been found to be upregulated in oral squamous
      cell carcinoma (OSCC). We hypothesized that there was an important relationship
      between miR-222 and PUMA in OSCC based on the prediction of the target genes of
      miR-222. In the present study, Pre-miR-222, As-miR-222 and the empty vector, were
      used to treat OSCC cells, respectively. Using the non-transfected cells as blank
      control, the expression levels of miR-222 and the PUMA gene were evaluated by RT
      PCR and western blotting. Cell proliferation and migration abilities were
      analyzed by MTT and Transwell assays. Cell cycle distribution and apoptosis were
      assessed by flow cytometry. Our results demonstrated that, when compared with the
      blank control group, OSCC cells in the Pre-miR-222 transfection group showed
      increased expression of miR-222 and decreased expression of PUMA, enhanced
      proliferation and invasion abilities, and decreased apoptosis. In contrast, the
      above indices in the As-miR-222 transfection group confirmed the opposite results
      when compared with those in the Pre-miR-222 transfection group. In addition, no
      significant differences between the empty vector transfection group and the
      control group were noted. Our results suggest that miR-222 targets the expression
      of PUMA in OSCC cells and affects cell growth, invasive and apoptotic abilities.
      Thus, PUMA may be a possible new target for the treatment of OSCC. 

PMID- 24452417
TI  - Effects of animacy and noun-phrase relatedness on the processing of complex
      sentences.
AB  - Previous work has suggested that syntactically complex object-extracted relative
      clauses are easier to process when the head noun phrase (NP1) is inanimate and
      the embedded noun phrase (NP2) is animate, as compared with the reverse animacy
      configuration, with differences in processing difficulty beginning as early as
      NP2 (e.g., The article that the senator . . . vs. The senator that the article .
      . .). Two eye-tracking-while-reading experiments were conducted to better
      understand the source of this effect. Experiment 1 showed that having an
      inanimate NP1 facilitated processing even when NP2 was held constant. Experiment
      2 manipulated both animacy of NP1 and the degree of semantic relatedness between
      the critical NPs. When NP1 and NP2 were paired arbitrarily, the early animacy
      effect emerged at NP2. When NP1 and NP2 were semantically related, this effect
      disappeared, with effects of NP1 animacy emerging in later processing stages for
      both the related and arbitrary conditions. The results indicate that differences
      in the animacy of NP1 influence early processing of complex sentences only when
      the critical NPs share no meaningful relationship. 

PMID- 24452418
TI  - Six persistent research misconceptions.
AB  - Scientific knowledge changes rapidly, but the concepts and methods of the conduct
      of research change more slowly. To stimulate discussion of outmoded thinking
      regarding the conduct of research, I list six misconceptions about research that
      persist long after their flaws have become apparent. The misconceptions are: 1)
      There is a hierarchy of study designs; randomized trials provide the greatest
      validity, followed by cohort studies, with case-control studies being least
      reliable. 2) An essential element for valid generalization is that the study
      subjects constitute a representative sample of a target population. 3) If a term
      that denotes the product of two factors in a regression model is not
      statistically significant, then there is no biologic interaction between those
      factors. 4) When categorizing a continuous variable, a reasonable scheme for
      choosing category cut-points is to use percentile-defined boundaries, such as
      quartiles or quintiles of the distribution. 5) One should always report P values
      or confidence intervals that have been adjusted for multiple comparisons. 6)
      Significance testing is useful and important for the interpretation of data.
      These misconceptions have been perpetuated in journals, classrooms and textbooks.
      They persist because they represent intellectual shortcuts that avoid more
      thoughtful approaches to research problems. I hope that calling attention to
      these misconceptions will spark the debates needed to shelve these outmoded ideas
      for good. 

PMID- 24452419
TI  - Elevated liver enzymes indicating a diagnosis of limb-girdle muscular dystrophy.
AB  - A 27-year-old man presented to an internal medicine clinic to establish primary
      care. His past medical history was significant for elevated liver transaminases
      found during laboratory monitoring while taking isotretinoin for acne. He had an
      extensive workup spanning 7 years including serial hepatic function panels after
      withholding isotretinoin, viral serologies, and two liver biopsies, which
      eventually led to a diagnosis of an idiopathic elevation in serum transaminases.
      During his present evaluation, he endorsed complaints of significant muscle
      soreness with strenuous activity despite conditioning. Creatine kinase was found
      to be elevated at 11,778 U/l. Nerve conduction studies and electromyogram
      indicated a myopathy. DNA sequencing confirmed a diagnosis of limb-girdle
      muscular dystrophy. The aminotransferases are most notable for their association
      with liver pathology; however, they are also present in other tissues such as
      heart, kidney, and skeletal muscle. Muscle pathology, including the inherited
      muscular dystrophies, are often identified by elevations in creatine kinase, but
      can also be suggested by elevations of aminotransferases. This case illustrates
      that myopathies should be considered in patients with otherwise unexplained
      elevations in liver aminotransferases. 

PMID- 24452420
TI  - The right way to treat a woman.

PMID- 24452423
TI  - Calcitonin gene-related peptide and migraine with aura: A systematic review.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine
      pathophysiology. Most studies have focused on CGRP in relation to migraine
      without aura (MO). About one-third of migraine patients have attacks with aura
      (MA), and this is a systematic review of the current literature on CGRP and MA.
      METHODS: We performed a systematic literature search on MEDLINE for reports of
      CGRP and MA, covering basic science, animal and human studies as well as
      randomized clinical trials. RESULTS: The literature search identified 594
      citations, of which 38 contained relevant, original data. Plasma levels of CGRP
      in MA patients are comparable to MO, but CGRP levels varied among studies. A
      number of animal studies, including knock-ins of familial hemiplegic migraine
      (FHM) genes, have examined the relationship between CGRP and cortical spreading
      depression. In patients, CGRP does not trigger migraine in FHM, but is a robust
      trigger of migraine-like headache both in MA and MO patients. The treatment
      effect of CGRP antagonists are well proven in the treatment of migraine, but no
      studies have studied the effect specifically in MA patients. CONCLUSION: This
      systematic review indicates that the role of CGRP in MA is less studied than in
      MO. Further studies of the importance of CGRP for auras and migraine are needed.

PMID- 24452421
TI  - Does the declining lethality of gunshot injuries mask a rising epidemic of gun
      violence in the United States?
AB  - Recent mass shootings in the U.S. have reignited the important public health
      debate concerning measures to decrease the epidemic of gun violence.
      Editorialists and gun lobbyists have criticized the recent focus on gun violence,
      arguing that gun-related homicide rates have been stable in the last decade.
      While true, data from the U.S. Centers for Disease Control and Prevention also
      demonstrate that although gun-related homicide rates were stable between 2002 and
      2011, rates of violent gunshot injuries increased. These seemingly paradoxical
      trends may reflect the declining lethality of gunshot injuries brought about by
      surgical advances in the care of the patient with penetrating trauma. Focusing on
      gun-related homicide rates as a summary statistic of gun violence, rather than
      total violent gunshot injuries, can therefore misrepresent the rising epidemic of
      gun violence in the U.S. 

PMID- 24452422
TI  - Obeticholic acid: a new light in the shadows treating portal hypertension?

PMID- 24452424
TI  - Backbone (1)H, (13)C and (15)N resonance assignments of the human eukaryotic
      release factor eRF1.
AB  - Eukaryotic translation termination is mediated by two interacting release
      factors, eukaryotic class 1 release factor (eRF1) and eukaryotic class 3 release
      factor (eRF3), which act cooperatively to ensure efficient stop codon recognition
      and fast polypeptide release. eRF1 consisting of three well-defined functional
      domains recognizes all three mRNA stop codons located in the A site of the small
      ribosomal subunit and triggers hydrolysis of the ester bond of peptidyl-tRNA in
      the peptidyl transfer center of the large ribosomal subunit. Nevertheless,
      various aspects of molecular mechanism of translation termination in eukaryotes
      remain unclear. Elucidation of the structure and dynamics of eRF1 in solution is
      essential for understanding molecular mechanism of its function in translation
      termination. To approach this problem, here we report NMR backbone signal
      assignments of the human eRF1 (437 a.a., 50 kDa). 

PMID- 24452425
TI  - An environmental Escherichia albertii strain, DM104, induces protective immunity
      to Shigella dysenteriae in guinea pig eye model.
AB  - The environmental Escherichia albertii strain DM104, which cross-reacts
      serologically with Shigella dysenteriae was assessed for pathogenic properties,
      immunogenicity, and protective efficacy in different animal models to evaluate it
      as a vaccine candidate against S. dysenteriae, which causes the severe disease,
      shigellosis. The DM104 isolate was found to be non-invasive and did not produce
      any entero- or cyto-toxins. The strain also showed negative results in the mouse
      lethal activity assay. The non-pathogenic DM104 strain gave, however, a high
      protective efficacy as an ocularly administered vaccine in the guinea pig eye
      model against S. dysenteriae type 4 challenge. It also induced a high titer of
      serum IgG against S. dysenteriae type 4 whole cell lysate and lipopolysaccharide.
      Taken together, all these results indicate a good potential for the use of the
      DM104 as a live vaccine candidate against shigellosis. 

PMID- 24452426
TI  - Phenotypic switching in biofilm-forming marine bacterium Paenibacillus lautus
      NE3B01.
AB  - Biofilm-forming marine bacterium Paenibacillus lautus NE3B01 was isolated from a
      mangrove ecosystem, Odisha, India. This isolate formed a swarming type of colony
      pattern on the solid culture medium with 0.5-2 % agar. Phase contrast microscopy
      study of a growing colony of P. lautus on solid media and swarming pattern
      revealed the existence of two phenotypically distinct cells (i.e. cocci and rods)
      across the colonies. However, in actively growing planktonic culture, only rod
      shaped cells were observed. Biofilm growth studies (crystal violet assay) with
      the isolate showed significant biofilm formation by 6 h, and the detachment phase
      was observed after 18 h. Biofilm parameters (such as total biomass, roughness
      coefficient, biofilm thickness, etc.) of 24-h-old P. lautus biofilm were studied
      by confocal scanning laser microscopy (CSLM). The CSLM study showed that P.
      lautus formed a biofilm with an average thickness of 14.8 +/- 2.6 MUm, a high
      roughness coefficient (0.379 +/- 0.103) and surface to bio-volume ratio (4.59 +/-
      1.12 MUm(2)/MUm(3)), indicating a highly uneven topography of the biofilm. This
      also indicates that the 24-h-old biofilm is in dispersal phase. Scanning electron
      microphotographs of P. lautus also supported the existence of two distinct
      phenotypes of P. lautus. The current findings suggest that P. lautus has two
      vegetative phenotypes and to decongest the overcrowded biofilm the bacterium can
      switch over to motile rods from nonmotile cocci and vice versa.

PMID- 24452427
TI  - Analysis of the gut microbiota by high-throughput sequencing of the V5-V6 regions
      of the 16S rRNA gene in donkey.
AB  - Considerable evidence suggests that the gut microbiota is complex in many mammals
      and gut bacteria communities are essential for maintaining gut homeostasis. To
      date the research on the gut microbiota of donkey is surprisingly scarce.
      Therefore, we performed high-throughput sequencing of the 16S rRNA genes V5-V6
      hypervariable regions from gut fecal material to characterize the gut microbiota
      of healthy donkeys and compare the difference of gut microbiota between male and
      female donkeys. Sixty healthy donkeys (30 males and 30 females) were enrolled in
      the study, a total of 915,691 validated reads were obtained, and the bacteria
      found belonged to 21 phyla and 183 genera. At the phylum level, the bacterial
      community composition was similar for the male and female donkeys and
      predominated by Firmicutes (64 % males and 64 % females) and Bacteroidetes (23 %
      males and 21 % females), followed by Verrucomicrobia, Euryarchaeota,
      Spirochaetes, and Proteobacteria. At the genus level, Akkermansia was the most
      abundant genus (23 % males and 17 % females), followed by Sporobacter,
      Methanobrevibacter, and Treponema, detected in higher distribution proportion in
      males than in females. On the contrary, Acinetobacter and Lysinibacillus were
      lower in males than in females. In addition, six phyla and 15 genera were
      significantly different between the male and female donkeys for species
      abundance. These findings provide previously unknown information about the gut
      microbiota of donkeys and also provide a foundation for future investigations of
      gut bacterial factors that may influence the development and progression of
      gastrointestinal disease in donkey and other animals.

PMID- 24452428
TI  - [Communication preferences of oncology patients].
AB  - PURPOSE: After testing the psychometric properties of a new questionnaire that
      measures patient preferences for patient-physician communication (KOPRA
      questionnaire), the communication preferences of cancer patients were described.
      In order to do this, the preferences were differentiated according to
      sociodemographic subgroups and a comparison was made to the preferences of
      patients with chronic back pain and chronic ischaemic heart disease. METHODS:
      N=1,635 patients from 31 medical oncology practices were surveyed. For the KOPRA
      questionnaire, reliability, unidimensionality, and fit to the Rasch model were
      tested. Hierarchical models were used to conduct subgroup analyses and
      comparisons with other diseases. RESULTS: The psychometric properties of the
      KOPRA are satisfactory to good. For patients, the 4 communication domains
      (patient participation and patient orientation, effective and open communication,
      emotionally supportive communication, communication about personal circumstances)
      measured by the KOPRA questionnaire are equally important. Women generally have
      higher expectations of the physician's communicative behaviour. Affective
      communication is considerably more important for cancer patients than for back
      pain or cardiac patients. CONCLUSION: The KOPRA questionnaire is well suited for
      examining the communication preferences of cancer patients. In general, physician
      behaviour associated with high scores in all 4 KOPRA dimensions is optimal.
      Especially in cases where the 4 communication aspects conflict with each other,
      the physician's communication style should be individualised.

PMID- 24452429
TI  - [Length of stay in institutionalised long-term care 1999-2011: a population-based
      study].
AB  - BACKGROUND AND OBJECTIVE: From the perspective of welfare economics,
      institutionalised long-term care (ILTC) is expensive and thus requires key
      figures. This article provides the population-based mean length of stay in ILTC,
      which is a meaningful measure for monitoring purposes. METHOD: The Sullivan
      method was applied to official statistics on population and long-term care
      between 1999 and 2011. This method splits up the life expectancy at birth into
      one part in and one part out of ILTC. The part in ILTC can be interpreted as
      length of stay. RESULTS: In 2011, males in Germany experienced 5.5 months in
      ILTC, females 14.4 months. In 1999, the length of stay was 3.8 and 11.8 months,
      respectively. Thus, the length of stay in ILTC has increased over time. However,
      the increase regarding women stopped in 2007. Furthermore, the onset of ILTC has
      been protracted. In 2011, the mean age at the start of ILTC was 77.6 years
      (males) and 81.7 years (females). In 1999 the mean age was 74.5 years (males) and
      79.9 years (females). In 2011, males spent 0.6% of their life expectancy in ILTC,
      females 1.4%. In 1999, this share was 0.4% (males) and 1.2% (females).
      CONCLUSIONS: The utilisation of ILTC needs to be monitored by meaningful key
      figures over time. The length of stay, as proposed here, provides information on
      life expectancy and ILTC prevalence collapsed into one measure. This article
      reports the length of stay and substantiates its increase over time (in women,
      the increase ended in 2007). It is recommended to regularly update the time
      series by using official statistics.

PMID- 24452430
TI  - [Verbal aggression against health-care staff: results of a qualitative study].
AB  - Verbal aggression against health-care staff can induce considerable stress.
      Compared to physical aggression, systematic studies on verbal aggression are
      lacking.A qualitative focus group study was conducted in several clinical
      settings in north-western Germany: acute mental health care, forensic mental
      health care, children and adolescent psychiatry, residential care for mentally
      ill persons, general hospital, and nursing home. 74 staff members from various
      professions participated in 8 focus groups.Various forms of verbal aggression
      were reported, from verbal abuse over threats to non-compliant behaviour.
      Backgrounds for verbal aggression by patients were usually non-satisfaction with
      the situation or the treatment, organisational problems, and mental disorders.
      Staff reported about various coping strategies such as ignorance and
      rationalisation, but also helplessness. Compared to physical aggression, the
      severity of verbal aggression was rated non-uniformly. A clear boundary between
      verbal aggression and 'normal' speech acts could not be drawn, as subjective and
      individual factors play an important role while interpreting aggressive
      acts.Verbal aggression is a relevant stressor for health-care staff which has
      been widely neglected in care institutions. Prevention efforts may include
      situational coping (e. g., communication training) and psychological coping (e.
      g., resilience enhancement). 

PMID- 24452431
TI  - [Transfer managment of postoperative acute pain therapy to outpatient aftercare].
AB  - The significance of postoperative pain management for patients in the hospital is
      well known and has been a focus of research for several years. The ambulatory
      care after hospital discharge, however, is not well investigated. A prospective
      observational study was therefore conducted to study the transfer management from
      in-hospital patients to ambulatory care. A patient questionnaire was developed
      and patients were asked to fill it out at different time points after the
      operation: during the time in the hospital, then at 2 weeks and 6 months after
      hospital discharge. In addition, the responsible family doctor was approached and
      interviewed. The main focus of the questionnaire was the measurement of post
      surgical pain (numeric rating scale NRS), patient satisfaction (Cologne patient
      questionnaire), and quality of life (SF 12). Of a total of 128 patients 72.9%
      described moderate to severe pain after the orthopaedic operations in the
      hospital. 90.8% of the patients had pain directly after discharge from the
      hospital; in 67.4% of the cases pain was >=3 and in 23.4% of the cases pain was
      >=6. Six months after discharge pain was significant in 29.4% of the patients,
      60.8% of the patients were satisfied with the transfer to the home setting. 16%
      were not satisfied at all and 23.2% were neutral. Important factors for
      dissatisfaction with the transfer management were, according to stepwise logistic
      regeression analysis, sex (female patients), young age, a poor bodily
      constitution at the hospital and thereafter, and the pain management in the
      hospital and after discharge. The study shows the significance of the acute pain
      therapy not only during the hospital stay but also after discharge. There are
      very few data on pain therapy after discharge from the hospital. Based on the
      significance of the chronification of acute pain it is of the utmost importance
      to close this gap. 

PMID- 24452432
TI  - Bridging dermatologists with patient advocacy organizations through smartphones.
AB  - IMPORTANCE: Patient advocacy organizations seek to increase their benefits for
      patients with skin disease; low awareness and patient referrals among
      dermatologists have presented an obstacle to this. OBJECTIVE: To determine
      whether the Skin Advocate iPhone App would increase awareness and referrals to
      patient advocacy organizations in the Coalition of Skin Diseases (CSD) among
      Texas dermatologists and dermatology residents and patient registrations among
      CSD member organizations. DESIGN, SETTING, AND PARTICIPANTS: We present results
      of an institutional review board-exempted investigation conducted among member
      organizations of the CSD and among dermatologists and dermatology residents in
      Texas from April 1, 2011, through March 31, 2013. Effects were measured in a
      blinded fashion subjectively through pre-intervention and post-intervention
      surveys and objectively through internal analytics that tracked downloads and use
      of the iPhone app, as well as pre-intervention and post-intervention numbers of
      registrations for CSD member organizations. INTERVENTION: The Skin Advocate
      iPhone App. MAIN OUTCOMES AND MEASURES: Awareness and referrals to patient
      advocacy organizations in the CSD among Texas dermatologists and dermatology
      residents and patient registrations among CSD member organizations. RESULTS:
      Throughout the study, mean app use ranged from 3.3 to 3.6 uses per user per
      month, maintaining the 3-fold improvement compared with self-reported referral
      for 90% of the study population and a 12-fold improvement for 64% of the study
      population. Our data revealed substantial improvement in self-reported physician
      awareness and referrals, and increased patient registrations for CSD
      organizations. CONCLUSIONS AND RELEVANCE: The Skin Advocate iPhone App improved
      physician awareness and subsequent referrals to CSD member organizations.

PMID- 24452433
TI  - Glycemic Control in US Immigrant and Nonimmigrant Black Youth with Type 1
      Diabetes.
AB  - Differences in glycemic control based on race have been reported in pediatric
      populations with type 1 diabetes (T1D). It is unknown if differences exist
      between pediatric populations within the same race classification. This
      retrospective study identified all immigrant and nonimmigrant Black youth
      diagnosed with T1D and treated at Seattle Children's Hospital from 2001 to 2011.
      Demographic characteristics and hemoglobin A1c (HbA1c) levels at 12, 24, and 36
      months post diagnosis were obtained from existing medical records. Immigrant
      youth had lower mean HbA1c levels at all three time points. The ethnicity effect
      on mean HbA1c levels approached significance at 36 months. When comparing 12 and
      36 months, the time effect was significant; the ethnicity effect approached
      significance. Clinically important differences may exist in glycemic control
      between pediatric populations with T1D from the same race classification.
      Additional work is needed to confirm these findings and determine potential
      causes. 

PMID- 24452434
TI  - Medial opening-wedge high tibial osteotomy fixation with short plate without any
      graft, synthetic material or spacer.
AB  - PURPOSE: Medial opening-wedge high tibial osteotomy (MOWHTO) is an effective
      surgical procedure for patients who have medial compartmental osteoarthritis of
      the knee with varus deformity of the limb. The abnormal load on the medial
      compartment of the knee is directed to the lateral compartment with this
      procedure. A gap occurs on the proximal tibia while providing adequate
      correction. Filling this gap with bone grafts or synthetic materials has gained
      wide acceptance for preventing bone union problems or osteotomy site collapse.
      The aim of this study is to report our results of MOWHTOs performed without any
      bone graft or any other synthetic materials. METHODS: We evaluated 41 MOWHTOs
      that have been performed between 2009 and 2012 with no use of any grafts or
      synthetic materials and spacer. Age of the patients ranged from 43 to 67. Thirty
      five of the patients were females and three of them were males. The follow-up
      time was 6 months. RESULTS: Seven knees had opening at the osteotomy site <10 mm,
      26 knees had 10-12.5 mm, and eight knees had >12.5 mm (range 7.5-14 mm, mean
      11.07 mm). All osteotomies united without loss of correction. The mean bone union
      time was 12.8 weeks. We did not have any major complication regarding the
      technique. CONCLUSION: The results of our study have shown that we can achieve
      satisfactory and good results by performing MOWHTO procedure without using any
      bone grafts or synthetic materials and spacer.

PMID- 24452436
TI  - Technical note: cervical dimensions for in situ and loose teeth: a critique of
      the Hillson et al. (2005) method.
AB  - In 2005, Hillson and colleagues developed a method for obtaining cervicometrics
      on a collection of loose teeth. However, I identified problems with the method
      when trying to apply it to material from archaeological collections with a
      mixture of in situ and loose teeth. The correct placement of the caliper tips at
      the suggested mesiodistal landmarks proved impossible for many in situ teeth.
      Their recommendation to rotate teeth to access the suggested landmarks resulted
      in large errors because not all teeth could be rotated. Other problems were
      identified with the suggested buccolingual dimensions of molars, which produced
      measurements that are not homologous across tooth class because of differential
      reduction in the distal cusps.

PMID- 24452437
TI  - Lipid charge regulation of non-specific biological ion channels.
AB  - Ion channels are specialized proteins that enable the movement of charges through
      otherwise impermeable lipidic membranes. Their action is essential in living
      organisms facilitating electric signaling, muscle contraction or osmotic stress
      response among other effects. The protein and the lipid charges configure a
      polarized interface that yields local ionic concentrations and electric
      potentials that are very different from those of the bulk electrolyte. The
      combined effect of gradients of ionic concentration and electric potential causes
      the transport of ions through channels. Here we analyze charge regulation effects
      in different protein-lipid conformations, stressing how important is the role of
      electrostatic interactions in the ion channel function that traditionally has
      been rationalized paying attention mainly to changes in pore size. Tuning lipid
      charge combined with conductance and selectivity measurements is shown to be a
      complementary method to evidence lipid involvement in the structure of a
      biological ion channel. 

PMID- 24452435
TI  - Chronic spinal cord electrical stimulation protects against 6-hydroxydopamine
      lesions.
AB  - Although L-dopa continues to be the gold standard for treating motor symptoms of
      Parkinson's disease (PD), it presents long-term complications. Deep brain
      stimulation is effective, but only a small percentage of idiopathic PD patients
      are eligible. Based on results in animal models and a handful of patients, dorsal
      column stimulation (DCS) has been proposed as a potential therapy for PD. To
      date, the long-term effects of DCS in animal models have not been quantified.
      Here, we report that DCS applied twice a week in rats treated with bilateral 6
      OHDA striatal infusions led to a significant improvement in symptoms. DCS-treated
      rats exhibited a higher density of dopaminergic innervation in the striatum and
      higher neuronal cell count in the substantia nigra pars compacta compared to a
      control group. These results suggest that DCS has a chronic therapeutical and
      neuroprotective effect, increasing its potential as a new clinical option for
      treating PD patients. 

PMID- 24452438
TI  - The impact of population structure on genomic prediction in stratified
      populations.
AB  - Impacts of population structure on the evaluation of genomic heritability and
      prediction were investigated and quantified using high-density markers in diverse
      panels in rice and maize. Population structure is an important factor affecting
      estimation of genomic heritability and assessment of genomic prediction in
      stratified populations. In this study, our first objective was to assess effects
      of population structure on estimations of genomic heritability using the
      diversity panels in rice and maize. Results indicate population structure
      explained 33 and 7.5% of genomic heritability for rice and maize, respectively,
      depending on traits, with the remaining heritability explained by within
      subpopulation variation. Estimates of within-subpopulation heritability were
      higher than that derived from quantitative trait loci identified in genome-wide
      association studies, suggesting 65% improvement in genetic gains. The second
      objective was to evaluate effects of population structure on genomic prediction
      using cross-validation experiments. When population structure exists in both
      training and validation sets, correcting for population structure led to a
      significant decrease in accuracy with genomic prediction. In contrast, when
      prediction was limited to a specific subpopulation, population structure showed
      little effect on accuracy and within-subpopulation genetic variance dominated
      predictions. Finally, effects of genomic heritability on genomic prediction were
      investigated. Accuracies with genomic prediction increased with genomic
      heritability in both training and validation sets, with the former showing a
      slightly greater impact. In summary, our results suggest that the population
      structure contribution to genomic prediction varies based on prediction
      strategies, and is also affected by the genetic architectures of traits and
      populations. In practical breeding, these conclusions may be helpful to better
      understand and utilize the different genetic resources in genomic prediction.

PMID- 24452440
TI  - Synthesis and characterization of copper(II) 4'-phenyl-terpyridine compounds and
      catalytic application for aerobic oxidation of benzylic alcohols.
AB  - The reactions between 4'-phenyl-terpyridine (L) and nitrate, acetate or chloride
      Cu(II) salts led to the formation of [Cu(NO3)2L] (1), [Cu(OCOCH3)2L].CH2Cl2
      (2.CH2Cl2) and [CuCl2L].[Cu(Cl)(MU-Cl)L]2 (3), respectively. Upon dissolving 1 in
      mixtures of DMSO-MeOH or EtOH-DMF the compounds [Cu(H2O){OS(CH3)2}L](NO3)2 (4)
      and [Cu(HO)(CH3CH2OH)L](NO3) (5) were obtained, in this order. Reaction of 3 with
      AgSO3CF3 led to [CuCl(OSO2CF3)L] (6). The compounds were characterized by ESI-MS,
      IR, elemental analysis, electrochemical techniques and, for 2-6, also by single
      crystal X-ray diffraction. They undergo, by cyclic voltammetry, two single
      electron irreversible reductions assigned to Cu(II) -> Cu(I) and Cu(I) -> Cu(0)
      and, for those of the same structural type, the reduction potential appears to
      correlate with the summation of the values of the Lever electrochemical EL ligand
      parameter, which is reported for the first time for copper complexes. Complexes 1
      6 in combination with TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxyl radical) can
      exhibit a high catalytic activity, under mild conditions and in alkaline aqueous
      solution, for the aerobic oxidation of benzylic alcohols. Molar yields up to 94%
      (based on the alcohol) with TON values up to 320 were achieved after 22 h.

PMID- 24452439
TI  - Cloning of seed dormancy genes (TaSdr) associated with tolerance to pre-harvest
      sprouting in common wheat and development of a functional marker.
AB  - KEY MESSAGE: After cloning and mapping of wheat TaSdr genes, both the functional
      markers for TaSdr - B1 and TaVp - 1B were validated, and the distribution of
      allelic variations at TaSdr - B1 locus in the wheat cultivars from 19 countries
      was characterized. Seed dormancy is a major factor associated with pre-harvest
      sprouting (PHS) in common wheat (Triticum aestivum L.). Wheat TaSdr genes,
      orthologs of OsSdr4 conferring seed dormancy in rice, were cloned by a
      comparative genomics approach. They were located on homoeologous group 2
      chromosomes, and designated as TaSdr-A1, TaSdr-B1 and TaSdr-D1, respectively.
      Sequence analysis of TaSdr-B1 revealed a SNP at the position -11 upstream of the
      initiation codon, with bases A and G in cultivars with low and high germination
      indices (GI), respectively. A cleaved amplified polymorphism sequence marker
      Sdr2B was developed based on the SNP, and subsequently functional analysis of
      TaSdr-B1 was conducted by association and linkage mapping. A QTL for GI co
      segregating with Sdr2B explained 6.4, 7.8 and 8.7 % of the phenotypic variances
      in a RIL population derived from Yangxiaomai/Zhongyou 9507 grown in Shijiazhuang,
      Beijing and the averaged data from those environments, respectively. Two sets of
      Chinese wheat cultivars were used for association mapping, and results indicated
      that TaSdr-B1 was significantly associated with GI. Analysis of the allelic
      distribution at the TaSdr-B1 locus showed that the frequencies of TaSdr-B1a
      associated with a lower GI were high in cultivars from Japan, Australia,
      Argentina, and the Middle and Lower Yangtze Valley Winter Wheat Region and
      Southwest Winter Wheat Region in China. This study provides not only a reliable
      functional marker for molecular-assisted selection of PHS in wheat breeding
      programs, but also gives novel information for a comprehensive understanding of
      seed dormancy.

PMID- 24452441
TI  - Key considerations for the success of Medical Education Research and Innovation
      units in Canada: unit director perceptions.
AB  - Growth in the field of medical education is evidenced by the proliferation of
      units dedicated to advancing Medical Education Research and Innovation (MERI).
      While a review of the literature discovered narrative accounts of MERI unit
      development, we found no systematic examinations of the dimensions of and
      structures that facilitate the success of these units. We conducted qualitative
      interviews with the directors of 12 MERI units across Canada. Data were analyzed
      using qualitative description (Sandelowski in Res Nurs Health 23:334-340, 2000).
      Final analysis drew on Bourdieu's (Outline of a theory of practice. Cambridge
      University Press, Cambridge, 1977; Media, culture and society: a critical reader.
      Sage, London, 1986; Language and symbolic power. Harvard University Press,
      Cambridge, 1991) concepts of field, habitus, and capital, and more recent
      research investigating the field of MERI (Albert in Acad Med 79:948-954, 2004;
      Albert et al. in Adv Health Sci Educ 12:103-115, 2007). When asked about the
      metrics by which they define their success, directors cited: teaching, faculty
      mentoring, building collaborations, delivering conference presentations, winning
      grant funding, and disseminating publications. Analyzed using Bourdieu's
      concepts, these metrics are discussed as forms of capital that have been
      legitimized in the MERI field. All directors, with the exception of one,
      described success as being comprised of elements (capital) at both ends of the
      service-research spectrum (i.e., Albert's PP-PU structure). Our analysis
      highlights the forms of habitus (i.e., behaviors, attitudes, demeanors) directors
      use to negotiate, strategize and position the unit within their local context.
      These findings may assist institutions in developing a new-or reorganizing an
      existing-MERI unit. We posit that a better understanding of these complex social
      structures can help units become savvy participants in the MERI field. With such
      insight, units can improve their academic output and their status in the MERI
      context-locally, nationally, and internationally. 

PMID- 24452442
TI  - Exploring features of integrative teaching through a microanalysis of connection
      making processes in a health sciences curriculum.
AB  - The interconnected nature of knowledge in the health sciences is not always
      reflected in how curricula, courses, and learning activities are designed. Thus
      have scholars advocated for more explicit attention to connection-making, or
      integration, in teaching and learning. However, conceptual and empirical work to
      guide such efforts is limited. This study analyzed classroom processes to
      determine what connections educators promoted in their classrooms and how those
      connections were made. A qualitative, focused ethnography design explored
      connection-making in a health science curriculum. Eight instructors were observed
      during ten class sessions resulting in 35 h of video data. Video data were
      entered into the observational software, Noldus Observer, and coded using
      continuous sampling. Frequency and duration of connections made were calculated
      in Noldus. Connection-making involved four interactive elements: The topic under
      direct consideration, other domains of professional knowledge (practice, student
      experience, research, theory, other content, core construct of the profession,
      external influences, metacognition), the integrative processes instructors used
      to connect a topic to other knowledge domains (informal example, stories,
      questioning, linking statements, formal cases, and program descriptions), and the
      learning and instructor context (type and purpose of course, instructor personal
      and professional experience). These elements are presented as an initial
      integrative learning taxonomy that can be used to guide explicit attention to
      connection-making in education and research.

PMID- 24452443
TI  - Resigned professionalism? Non-acute inpatients and resident education.
AB  - A growing group of inpatients on acute clinical teaching units have non-acute
      needs, yet require attention by the team. While anecdotally, these patients have
      inspired frustration and resource pressures in clinical settings, little is known
      about the ways in which they influence physician perceptions of the learning
      environment. This qualitative study explored residents' and attending physicians'
      perceptions of caring for these patients, including their educational value.
      Using constructivist grounded theory, we conducted seven homogeneous focus groups
      and three interviews with residents and attending physicians from neurology and
      general internal medicine. A constant comparative analytical approach was
      employed alongside data collection, using theoretical sampling to explore
      emergent themes. Residents consistently described non-acute patients as non
      educational, uninteresting, but still in need of care. Some attending physicians
      echoed this view, while others described multiple learning opportunities
      presented by non-acute patients. Both groups described residents as engaging with
      non-acute patients in a professional capacity, but not as learners. This
      engagement in a professional capacity could be considered diligent disinterest,
      or resigned professionalism. A constructivist understanding of the dynamics which
      influence learning in the workplace was used to explore the reasons why the
      residents in our study did not recognize the learning opportunities presented by
      non-acute patients. Our results resonate with Billett's theory of workplace
      affordances, which offers an explanation as to why learners may not identify or
      take advantage of potential learning opportunities. Overall, our study assists
      our understanding of the sociocultural factors that influence learners' choices
      to engage with particular clinical learning opportunities. 

PMID- 24452444
TI  - Expedient access to substituted 3-amino-2-cyclopentenones by dirhodium-catalyzed
      [3+2]-annulation of silylated ketene imines and enoldiazoacetates.
AB  - In a reaction that proceeds under mild conditions with remarkable functional
      group tolerance, structurally diverse 3-amino-2-cyclopentenones bearing a
      quaternary carbon at the 4-position have been synthesized through a formal [3+2]
      cycloaddition reaction of silylated ketene imines (SKIs) and enoldiazoaceates by
      dirhodium catalysis. 

PMID- 24452445
TI  - Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human
      osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest.
AB  - The overexpression of Aurora kinase A (AURKA), a member of serine/threonine
      kinase family, has been observed in various types of human cancers. However, the
      role of AURKA in osteosarcoma (OS), the most common type of primary malignancy
      arising from bone, has not been clarified. We used AURKA-specific lentivirus
      delivered short hairpin RNA (shRNA) to significantly and sustainably silence the
      endogenous AURKA expression in human OS cells SAOS-2 and U2OS. We found that
      AURKA downregulation in OS cells prominently decreased colony formation ability
      in vitro and tumorigenesis ability in vivo. We further evaluated the effect of
      AURKA silence on cell viability by MTT assay, cell apoptosis and cell cycle by
      flow cytometer detection. The results showed that AURKA silence inhibited cell
      viability by inducing cell apoptosis and G2/M cell cycle arrest in OS cells.
      Taken together, our findings indicate that AURKA plays a crucial role on OS
      growth by inhibiting cell apoptosis and propelling cell cycle. Inhibition of
      AURKA by lentivirus-delivered specific shRNA showed the therapeutic potential in
      treatment of osteosarcoma.

PMID- 24452446
TI  - Early body weight loss during concurrent chemo-radiotherapy for non-small cell
      lung cancer.
AB  - BACKGROUND AND PURPOSE: Radiation-esophagitis and weight loss are frequently
      observed toxicities in patients treated with concurrent chemo-radiotherapy (CT
      RT) for non-small cell lung cancer (NSCLC) and might be related. The purpose was
      to investigate whether weight loss already starts early after initiation of CT-RT
      and precedes radiation-esophagitis. MATERIALS AND METHODS: In a retrospective
      cohort, weight and esophagitis grade >=2 were assessed during the first weeks of
      (CT-)RT in patients treated with concurrent (n = 102) or sequential (n = 92)
      therapy. In a prospective validation study, data on body weight, esophagitis
      grade >=2, nutritional intake and muscle strength were obtained before, during
      and following CT-RT. RESULTS: In the retrospective cohort, early weight loss was
      observed in concurrently treated patients (p = 0.002), independent of esophagitis
      >= grade 2. Early weight loss was also observed in the prospective cohort (p =
      0.003) and was not accompanied by decreases in nutritional intake. In addition
      lower limb muscle strength rapidly declined (p = 0.042). In the later weeks of
      treatment, further body weight loss occurred (p < 0.001) despite increased
      nutritional supplementation and body weight was only partly recovered after 4
      weeks post CT-RT (p = 0.003). CONCLUSIONS: Weight loss during concurrent CT-RT
      for NSCLC starts early and prior to onset of esophagitis, requiring timely and
      intense nutritional rehabilitation.

PMID- 24452447
TI  - Overexpression of fibronectin confers cell adhesion-mediated drug resistance (CAM
      DR) against 5-FU in oral squamous cell carcinoma cells.
AB  - The tumor-associated microenvironment has been shown to protect tumor cells from
      treatment, and the extracellular matrix (ECM) is known to affect drug resistance
      as a key regulator of the tumor microenvironment. However, little is known about
      cell adhesion-mediated drug resistance (CAM-DR) due to cell-ECM contact in
      patients with oral squamous cell carcinoma (OSCC). In the present study, we
      evaluated the ECM molecule fibronectin (FN) using DNA microarray data obtained
      from parental and 5-FU-resistant OSCC cell lines. We investigated the effects of
      cell adhesion to FN on 5-FU resistance in OSCC cells and examined the activation
      of FN receptor beta1 integrin-mediated survival regulators such as ILK, Akt and
      NF-kappaB. In addition, we investigated whether FNIII14, a 22-mer peptide derived
      from FN that potently prevents beta1 integrin-mediated adhesion to FN, could
      overcome CAM-DR against 5-FU in OSCC cells and examined the activation of
      survival regulators and apoptosis-related molecules. Consequently, we obtained
      the following results. FN was extracellularly overexpressed in the 5-FU-resistant
      cells compared with that observed in the 5-FU-sensitive cells. Cell adhesion to
      FN enhanced 5-FU resistance and activated integrin-mediated ILK/Akt/NF-kappaB
      survival signaling in the 5-FU-resistant OSCC cells. Furthermore, the inhibition
      of cell adhesion to FN by FNIII14 enhanced chemosensitivity to 5-FU and apoptosis
      by suppressing ILK/Akt/NF-kappaB signaling in the 5-FU-resistant cells. These
      novel findings demonstrate that FN is a potentially useful biomarker and
      therapeutic target for improving the treatment of OSCC, particularly in the
      setting of 5-FU resistance.

PMID- 24452448
TI  - FDA acts to limit exposure to acetaminophen in combination products.

PMID- 24452449
TI  - Healthcare-associated urinary tract infections in hospitalized urological
      patients--a global perspective: results from the GPIU studies 2003-2010.
AB  - INTRODUCTION: European Section for Infections in Urology has been conducting an
      annual prevalence survey investigating various aspects of healthcare-associated
      urinary tract infections (HAUTI) since 2003. MATERIAL AND METHODS: The data on
      various clinical categories of HAUTI, the contamination status of HAUTI patients
      who underwent any urological intervention with regard to microorganisms isolated,
      resistance status and antibiotics used to treat HAUTI will be presented. RESULTS:
      Of a total of 19,756 patients screened, 1,866 patients had HAUTI (9.4 %); 1,313
      males (70.4 %) and 553 (29.6 %) females. Mean age was 59.9 +/- 18.2. Asymptomatic
      bacteriuria (ASB) and cystitis were the most frequent clinical diagnoses
      representing 27.0 and 26 % of all HAUTI, respectively. Echerichia coli was found
      to be the most frequent uropathogen (544 of 1,371 isolates) (39.7 %).
      Fluoroquinolones were preferred in 26.6 % of cases followed by cephalosporins
      (23.3 %), aminoglycosides (14.1 %) and penicillins (13.8 %). High global
      resistance rates to ciprofloxacin (>50 %), cephalosporins (35-50 %) and
      penicillins (50 %) were found in the GPIU studies 2003-2010. DISCUSSION: We
      showed that around 10 % of hospitalized urological patients are at risk to
      develop HAUTI often caused by multiresistant uropathogens. Increased antibiotic
      use often with broad-spectrum antimicrobials will inevitably be followed by
      increasing bacterial resistance. To interrupt such a vicious cycle, our results
      suggest (1) there is still room for improvement in surgical prophylaxis in terms
      of limiting exposure to antibiotics and (2) far too many patients with ASB are
      being treated which shows that the new proposal of classification should be
      adopted where ABS is regarded as colonization and not as an infection to be
      treated.

PMID- 24452450
TI  - Is a wider angle of the membranous urethra associated with incontinence after
      radical prostatectomy?
AB  - PURPOSE: To investigate whether differences in the anatomy and dynamics of the
      pelvic floor (PF) in patients after radical prostatectomy (RP) depicted on
      magnetic resonance imaging (MRI) are associated with continence status. METHODS:
      In the prospective designed study, 24 patients with post-prostatectomy stress
      urinary incontinence were enrolled. Additionally, 10 continent patients after RP
      were matched for age, body mass index and perioperative parameters. All patients
      underwent continence assessment and MRI (TrueFISP sequence; TR 4.57 ms; TE 2.29
      ms; slice thickness 7 mm; FOV 270 mm) 12 months after RP. Images were analyzed
      for membranous urethra length (MUL), angle of the membranous urethra (AMU),
      severity of periurethral/urethral fibrosis, lifting of the levator ani muscle,
      lowering of the posterior bladder wall (BPW), bladder neck (BN) and external
      urinary sphincter (EUS), and symphyseal rotation of these structures during the
      Valsalva maneuver and voiding. RESULTS: Compared to continent controls,
      incontinent patients showed a significant wider AMU during voiding (p = 0.002)
      and more pronounced lowering of the BN and EUS (p < 0.001). No differences
      between the groups were found in symphyseal rotation of the analyzed structures,
      MUL and severity of periurethral/urethral fibrosis. CONCLUSIONS: The angle of the
      membranous urethra as a result of anchoring of the BN and EUS in the PF appears
      to be an important functional factor with an essential impact on continence after
      RP. Functional MRI seems to be a helpful imaging tool for morphologic and dynamic
      evaluation of the PF.

PMID- 24452451
TI  - An ethnographic study of participant roles in school bullying.
AB  - An ethnographic study in a 10th grade remedial class was undertaken in order to
      discern patterns of school bullying. Twenty 10th graders were observed over the
      course of one academic year as they interacted with their peers and teachers. The
      observations helped us identify dispositional and situational factors which
      influenced participant roles. In-depth interviews of students involved in school
      bullying showed how participants interpreted and explained their classroom
      behaviors. The analysis of the data gathered allowed the identification of four
      main actor roles recognized in the existing literature on bullying-the pure
      victim, the pure bully, the provocative-victim, and the bystander-as well as the
      differentiation between aggressive bullies and the bully managers. Most roles
      fluctuated according to specific circumstances and often appeared to be moderated
      by the teacher's management style and contextual variables. Some pupils assumed
      different roles in different contexts, sometimes changing roles within or between
      episodes. Teacher personality and style also had an impact on the frequencies and
      types of aggression and victimization. The use of an ethnographic research
      paradigm is discussed as an important supplement to positivistic studies of
      school bullying.

PMID- 24452452
TI  - Changes in lifestyle modestly reduce the estimated cardiovascular disease risk in
      one-year follow-up of the Finnish diabetes prevention program (FIN-D2D).
AB  - AIMS: The purpose of this study was to assess whether changes in self-rated
      physical activity and diet during a type 2 diabetes (T2D) prevention program were
      associated with changes in estimated 10-year risk for cardiovascular disease
      (CVD) events and mortality in people at high risk for T2D. METHODS: Individuals
      were identified and offered lifestyle counseling as part of the Finnish diabetes
      prevention program. Ten-year risk for estimated CVD events and mortality were
      calculated with Framingham Risk Score (FRS) and Systematic Coronary Risk
      Evaluation (SCORE) formula. FRS was available for 774 men and 1474 women and
      SCORE for 961 men and 1766 women. RESULTS: During the one-year follow-up, 9.6% of
      the men reported both an increase in physical activity and improved dietary
      pattern, 4.1% an increase in physical activity, 39.3% an increase in improved
      dietary pattern, while 47.0% reported no lifestyle changes. Corresponding numbers
      for women were 14.2%, 3.8%, 39.2% and 42.7%. Estimated 10-year risk for CVD
      events decreased 3.5% in men and 1.5% in women reporting an increase in physical
      activity and improvement in diet, compared to an increase of 0.15% in men
      (p<0.001, between groups) and decrease of 0.43% (p=0.027, between groups) in
      women with no lifestyle changes after adjustment for age and baseline FRS.
      Numbers needed to treat to prevent one CVD event by lifestyle changes were 25 for
      men and 59 for women. Lifestyle changes had no effect on estimated CVD mortality
      risk. CONCLUSIONS: Lifestyle counseling offered in primary health care for one
      year results in favorable changes in lifestyle, and lowered the estimated 10-year
      risk for CVD events.

PMID- 24452453
TI  - Regulation of body temperature and brown adipose tissue thermogenesis by bombesin
      receptor subtype-3.
AB  - Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, with Brs3
      knockout (Brs3(-/y)) mice being hypometabolic, hypothermic, and hyperphagic and
      developing obesity. We now report that the reduced body temperature is more
      readily detected if body temperature is analyzed as a function of physical
      activity level and light/dark phase. Physical activity level correlated best with
      body temperature 4 min later. The Brs3(-/y) metabolic phenotype is not due to
      intrinsically impaired brown adipose tissue function or in the communication of
      sympathetic signals from the brain to brown adipose tissue, since Brs3(-/y) mice
      have intact thermogenic responses to stress, acute cold exposure, and beta3
      adrenergic activation, and Brs3(-/y) mice prefer a cooler environment. Treatment
      with the BRS-3 agonist MK-5046 increased brown adipose tissue temperature and
      body temperature in wild-type but not Brs3(-/y) mice. Intrahypothalamic infusion
      of MK-5046 increased body temperature. These data indicate that the BRS-3
      regulation of body temperature is via a central mechanism, upstream of
      sympathetic efferents. The reduced body temperature in Brs3(-/y) mice is due to
      altered regulation of energy homeostasis affecting higher center regulation of
      body temperature, rather than an intrinsic defect in brown adipose tissue. 

PMID- 24452454
TI  - The biochemistry and cell biology of aging: metabolic regulation through
      mitochondrial signaling.
AB  - Cellular and organ metabolism affects organismal lifespan. Aging is characterized
      by increased risks for metabolic disorders, with age-associated degenerative
      diseases exhibiting varying degrees of mitochondrial dysfunction. The traditional
      view of the role of mitochondria generated reactive oxygen species (ROS) in
      cellular aging, assumed to be causative and simply detrimental for a long time
      now, is in need of reassessment. While there is little doubt that high levels of
      ROS are detrimental, mounting evidence points toward a lifespan extension effect
      exerted by mild to moderate ROS elevation. Dietary caloric restriction,
      inhibition of insulin-like growth factor-I signaling, and inhibition of the
      nutrient-sensing mechanistic target of rapamycin are robust longevity-promoting
      interventions. All of these appear to elicit mitochondrial retrograde signaling
      processes (defined as signaling from the mitochondria to the rest of the cell,
      for example, the mitochondrial unfolded protein response, or UPR(mt)). The
      effects of mitochondrial retrograde signaling may even spread to other
      cells/tissues in a noncell autonomous manner by yet unidentified signaling
      mediators. Multiple recent publications support the notion that an evolutionarily
      conserved, mitochondria-initiated signaling is central to the genetic and
      epigenetic regulation of cellular aging and organismal lifespan. 

PMID- 24452455
TI  - Insulinotropic effect of high potassium concentration beyond plasma membrane
      depolarization.
AB  - The question whether K+ depolarization is an appropriate experimental substitute
      for the physiological nutrient-induced depolarization of the beta-cell plasma
      membrane was investigated using primary mouse beta-cells and islets. At basal
      glucose 40 mM K+ induced a massive monophasic response, whereas 15 mM K+ had only
      a minimal insulinotropic effect, even though the increase in the cytosolic Ca2+
      concentration ([Ca2+]i) was not inferior to that by 20 mM glucose. In voltage
      clamp experiments, Ca2+ influx appeared as nifedipine-inhibitable inward action
      currents in the presence of sulfonylurea plus TEA to block compensatory outward
      K+ currents. Under these conditions, 15 mM K+ induced prolonged action currents
      and 40 mM K+ transformed the action current pattern into a continuous inward
      current. Correspondingly, 15 mM K+ led to an oscillatory increase and 40 mM K+ to
      a plateau of [Ca2+]i superimposed on the [Ca2+]i elevated by sulfonylurea plus
      TEA. Raising K+ to 15 or 40 mM in the presence of sulfonylurea (+/-TEA) led to a
      fast further increase of insulin secretion. This was reduced to basal levels by
      nifedipine or CoCl2. The effects of 15 mM K+ on depolarization, action currents,
      and insulin secretion were mimicked by adding 35 mM Cs+ and those of 40 mM K+ by
      adding 35 mM Rb+, in parallel with their ability to substitute for K+ as permeant
      cation. In conclusion, the alkali metals K+, Rb+, or Cs+ concentration
      dependently transform the pattern of Ca2+ influx into the beta-cell and may thus
      generate stimuli of supraphysiological strength for insulin secretion.

PMID- 24452456
TI  - The COP9 signalosome is a repressor of replicative stress responses and
      polyploidization in the regenerating liver.
AB  - Aberrant DNA replication induced by deregulated or excessive proliferative
      stimuli evokes a "replicative stress response" leading to cell cycle restriction
      and/or apoptosis. This robust fail-safe mechanism is eventually bypassed by
      transformed cells, due to ill-defined epistatic interactions. The COP9
      signalosome (CSN) is an evolutionarily conserved regulator of cullin ring ligases
      (CRLs), the largest family of ubiquitin ligases in metazoans. Conditional
      inactivation of the CSN in several tissues leads to activation of S- or G2-phase
      checkpoints resulting in irreversible cell cycle arrest and cell death. Herein we
      ablated COPS5, the CSNs catalytic subunit, in the liver, to investigate its role
      in cell cycle reentry by differentiated hepatocytes. Lack of COPS5 in
      regenerating livers causes substantial replicative stress, which triggers a
      CDKN2A-dependent genetic program leading to cell cycle arrest, polyploidy, and
      apoptosis. These outcomes are phenocopied by acute overexpression of c-Myc in
      COPS5 null hepatocytes of adult mice. CONCLUSION: We propose that combined
      control of proto-oncogene product levels and proteins involved in DNA replication
      origin licensing may explain the deleterious consequences of CSN inactivation in
      regenerating livers and provide insight into the pathogenic role of the
      frequently observed overexpression of the CSN in hepatocellular carcinoma.

PMID- 24452457
TI  - Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells
      under sub-lethal doses of oxidative stress.
AB  - The regenerative potential of mesenchymal stem cells (MSCs) is impaired by
      cellular senescence, a multi factorial process that has various functions.
      However, pathways and molecules involved in senescence have not been fully
      identified. Lipocalin 2 (Lcn2) has been the subject of intensive research, due to
      its contribution to many physiological and pathophysiological conditions. The
      implication of Lcn2 has been reported in many conditions where senescence also
      occurs. In the present study, we evaluated the role of Lcn2 in the occurrence of
      senescence in human bone marrow-derived mesenchymal stem cells (hB-MSCs) under
      oxidative conditions. When hB-MSCs were genetically engineered to over-express
      Lcn2 (MSC-Lcn2) and exposed to H2O2, the proliferation rate of the cells
      increased. However, the number of colonies and the number of cells that made up
      each colony in both MSC-V and MSC-Lcn2 cells decreased compared to those
      cultivated under normal conditions. Our results revealed that over-expression of
      recombinant Lcn2 in hB-MSCs decreases senescence induced by H2O2 treatment.
      Senescent cells were observed in aged hB-MSCs; however, no alteration in the
      expression level of Lcn2 was detected compared to earlier passages. Finally, a
      higher amount of Lcn2 protein was detected in the plasma of the elderly than in
      young people. Our findings suggest that Lcn2 might restore the health and
      regeneration potential of MSCs by decreasing senescence.

PMID- 24452458
TI  - Cdc37 engages in stable, S14A mutation-reinforced association with the most
      atypical member of the yeast kinome, Cdk-activating kinase (Cak1).
AB  - In most eukaryotes, Cdc37 is an essential chaperone, transiently associating with
      newly synthesised protein kinases in order to promote their stabilisation and
      activation. To determine whether the yeast Cdc37 participates in any stable
      protein interactions in vivo, genomic two-hybrid screens were conducted using
      baits that are functional as they preserve the integrity of the conserved N
      terminal region of Cdc37, namely a Cdc37-Gal4 DNA binding domain (BD) fusion in
      both its wild type and its S14 nonphosphorylatable (Cdc37(S14A)) mutant forms.
      While this failed to identify the protein kinases previously identified as Cdc37
      interactors in pull-down experiments, it did reveal Cdc37 engaging in a stable
      association with the most atypical member of the yeast kinome, cyclin-dependent
      kinase (Cdk1)-activating kinase (Cak1). Phosphorylation of the conserved S14 of
      Cdc37 is normally crucial for the interaction with, and stabilisation of, those
      protein kinase targets of Cdc37, Cak1 is unusual in that the lack of this Cdc37
      S14 phosphorylation both reinforces Cak1:Cdc37 interaction and does not
      compromise Cak1 expression in vivo. Thus, this is the first Cdc37 client kinase
      found to be excluded from S14 phosphorylation-dependent interaction. The unusual
      stability of this Cak1:Cdc37 association may partly reflect unique structural
      features of the fungal Cak1. 

PMID- 24452459
TI  - Diterpene alkaloids from the roots of Aconitum moldavicum and assessment of Nav
      1.2 sodium channel activity of aconitum alkaloids.
AB  - A new aconitane alkaloid, 1-O-demethylswatinine (1), was isolated from the root
      of Aconitum moldavicum together with the known compounds cammaconine (2),
      columbianine (3), swatinine (4), gigactonine (5), delcosine (6), lycoctonine (7),
      and ajacine (8). The structures were established by means of HRESIMS, 1D and 2D
      NMR spectroscopy, including 1H-1H COSY, NOESY, HSQC, and HMBC experiments,
      resulting in complete 1H-NMR chemical shift assignments for 1-4. The effects of
      the isolated compounds 4-8, together with eighteen other Aconitum diterpene and
      norditerpene alkaloids with different skeletal types and substitution patterns,
      were studied on Nav 1.2 channels by the whole-cell patch clamp technique, using
      the QPatch-16 automated patch clamp system. Pyroaconitine, ajacine,
      septentriodine, and delectinine demonstrated significant Nav 1.2 channel
      inhibition (57-42 %) at 10 uM concentration; several other compounds
      (acovulparine, acotoxicine, hetisinone, 14-benzoylaconine-8-O-palmitate,
      aconitine, and lycoctonine) exerted moderate inhibitory activity (30-22 %), while
      the rest of the tested alkaloids were considered to be inactive. On the basis of
      these results and by exhaustive comparison of data of previously published
      computerized QSAR studies on diterpene alkaloids, certain conclusions on the
      structure-activity relationships of Aconitum alkaloids concerning Nav 1.2 channel
      inhibitory activity are proposed. 

PMID- 24452460
TI  - In vitro and in vivo studies of trypanocidal activity of dietary isothiocyanates.
AB  - Six dietary isothiocyanates, allyl-isothiocyanate, benzyl-isothiocyanate,
      phenylethyl-isothiocyanate, sulforaphane, erucin, and iberin, were tested for
      their trypanocidal activities in vitro using culture-adapted bloodstream forms of
      Trypanosoma brucei. All isothiocyanates showed a dose-dependent effect on the
      growth of trypanosomes. Five compounds displayed MIC values of 10 uM and GI50
      values of around 1.5 uM, while allyl-isothiocyanate exhibited values of 100 and
      11 uM, respectively. The compounds showed similar cytotoxic activities against
      human HL-60 cells with GI50 values of 1-4 uM and MIC values of 10-100 uM. Short
      term experiments revealed that, with the exception of allyl-isothiocyanate,
      isothiocyanates at a concentration of 10 uM kill trypanosomes within 1-4 h of
      incubation. In contrast, HL-60 cells were not affected by any of the compounds in
      short-term incubation experiments. Sulforaphane, the most intensively studied
      isothiocyanate, was also investigated for its in vivo trypanocidal activity.
      However, administration of 50 mg/kg sulforaphane orally or intraperitoneally for
      four days had no effect on the parasitaemia in mice infected with T. brucei
      compared to control animals treated with vehicle alone. 

PMID- 24452461
TI  - Cinchona alkaloids from Cinchona succirubra and Cinchona ledgeriana.
AB  - Seven new cinchona alkaloids, cinchonanines A-G (1-7), and 29 known alkaloids
      were isolated from the barks of Cinchona surrirubra and C. ledgeriana collected
      from Yunnan Province in China. The new structures were elucidated by extensive
      spectroscopic analysis. All compounds were evaluated for their cytotoxicity
      against five human cancer cell lines. Compounds 2, 13, 14, and 15 showed moderate
      cytotoxicity. 

PMID- 24452462
TI  - Pharmacokinetic Interaction of astragaloside IV with atractylenolide I and prim-O
      glucosylcimifugin in male Sprague Dawley rats.
AB  - Astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin are main
      medicinal components of the traditional Chinese medicine prescription Yu-ping
      feng which is composed of three herbs: Astragalus membranaceus, Atractylodes
      macrocephala, and Saposhnikovia divaricata. This study is aimed to assess the
      influence of atractylenolide I and prim-O-glucosylcimifugin on the
      pharmacokinetic profile of astragaloside IV so as to investigate the
      pharmacokinetic mechanisms of the Yu-ping-feng prescription. Fifteen Sprague
      Dawley rats were randomized to three groups; astragaloside IV, astragaloside IV
      plus atractylenolide I, and a combination of astragaloside IV, atractylenolide I,
      and prim-O-glucosylcimifugin were respectively administered to rats of these
      three groups via intragastric gavage. Serum samples were collected at different
      times after drug administration, and serum concentrations of astragaloside IV and
      atractylenolide I were simultaneously detected using HPLC-electrospray ionization
      MS. Compared with administration of astragaloside IV alone, concentrations of
      astragaloside IV in the serum were significantly increased when it was given in
      combination with atractylenolide I or atractylenolide I+prim-O-glucosylcimifugin,
      with higher values for Cmax (p = 0.019 and p = 0.033 compared with astragaloside
      IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O
      glucosylcimifugin groups, respectively) and AUC (p = 0.0052 and p = 0.0047
      compared with astragaloside IV + atractylenolide I and astragaloside IV +
      atractylenolide I + prim-O-glucosylcimifugin groups, respectively). Improvement
      in mean oral Cmax and mean systemic serum exposure because of the pharmacokinetic
      interaction between astragaloside IV and atractylenolide I might explain the
      rationale for the use of multiple herbs in Yu-ping-feng and of combinations of
      A.membranaceus and A. macrocephala. 

PMID- 24452463
TI  - RNA decay: stabilizing stemness through m6A.

PMID- 24452467
TI  - Gene expression: methyltransferases 'talk' at histone H3.

PMID- 24452468
TI  - Stem cells: moving out of the niche.

PMID- 24452469
TI  - A day in the life of the spliceosome.
AB  - One of the most amazing findings in molecular biology was the discovery that
      eukaryotic genes are discontinuous, with coding DNA being interrupted by
      stretches of non-coding sequence. The subsequent realization that the intervening
      regions are removed from pre-mRNA transcripts via the activity of a common set of
      small nuclear RNAs (snRNAs), which assemble together with associated proteins
      into a complex known as the spliceosome, was equally surprising. How do cells
      coordinate the assembly of this molecular machine? And how does the spliceosome
      accurately recognize exons and introns to carry out the splicing reaction?
      Insights into these questions have been gained by studying the life cycle of
      spliceosomal snRNAs from their transcription, nuclear export and re-import to
      their dynamic assembly into the spliceosome. This assembly process can also
      affect the regulation of alternative splicing and has implications for human
      disease. 

PMID- 24452470
TI  - Regulated protein turnover: snapshots of the proteasome in action.
AB  - The ubiquitin proteasome system (UPS) is the main ATP-dependent protein
      degradation pathway in the cytosol and nucleus of eukaryotic cells. At its centre
      is the 26S proteasome, which degrades regulatory proteins and misfolded or
      damaged proteins. In a major breakthrough, several groups have determined high
      resolution structures of the entire 26S proteasome particle in different
      nucleotide conditions and with and without substrate using cryo-electron
      microscopy combined with other techniques. These structures provide some
      surprising insights into the functional mechanism of the proteasome and will give
      invaluable guidance for genetic and biochemical studies of this key regulatory
      system. 

PMID- 24452471
TI  - Regulated necrosis: the expanding network of non-apoptotic cell death pathways.
AB  - Cell death research was revitalized by the understanding that necrosis can occur
      in a highly regulated and genetically controlled manner. Although RIPK1 (receptor
      interacting protein kinase 1)- and RIPK3-MLKL (mixed lineage kinase domain-like)
      mediated necroptosis is the most understood form of regulated necrosis, other
      examples of this process are emerging, including cell death mechanisms known as
      parthanatos, oxytosis, ferroptosis, NETosis, pyronecrosis and pyroptosis.
      Elucidating how these pathways of regulated necrosis are interconnected at the
      molecular level should enable this process to be therapeutically targeted.

PMID- 24452473
TI  - Regulation of GluA1 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptor function by protein kinase C at serine-818 and threonine-840.
AB  - Three residues within the AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid) receptor subunit GluA1 C terminus (Ser818, Ser831,
      Thr840) can be phosphorylated by Ca(2+)/phospholipid-dependent protein kinase
      (PKC). Here, we show that PKC phosphorylation of GluA1 Ser818 or Thr840 enhances
      the weighted mean channel conductance without altering the response time course
      or agonist potency. These data support the idea that these residues constitute a
      hyper-regulatory domain for the AMPA receptor. Introduction of phosphomimetic
      mutations increases conductance only at these three sites within the proximal C
      terminus, consistent with a structural model with a flexible linker connecting
      the distal C-terminal domain to the more proximal domain containing a helix
      bracketed by Ser831 and Thr840. NMR spectra support this model and raise the
      possibility that phosphorylation can alter the configuration of this domain. Our
      findings provide insight into the structure and function of the C-terminal domain
      of GluA1, which controls AMPA receptor function and trafficking during synaptic
      plasticity in the central nervous system. 

PMID- 24452474
TI  - Motivational orientation of people participating in vocational rehabilitation.
AB  - PURPOSE: The task of vocational rehabilitation is to support the employee's
      chances of continuing in working life. The study aimed to examine the
      motivational orientation of people participating in vocational rehabilitation and
      to find out what characteristics of the clients, their life situation, and their
      beliefs and perceptions were associated with it. METHODS: A mail questionnaire
      was answered by 839 rehabilitation clients who had received an affirmative
      rehabilitation decision under the earnings-related pension scheme 12 months
      earlier (response rate 67 %). Two variables depicting motivational orientation
      were formed, i.e., motivation for continuing in working life and motivation for
      participating in vocational rehabilitation. Logistic regression analyses were
      applied in examining the factors associated with each motivation variable.
      RESULTS: The results indicate that the two motivational orientations can be
      regarded as partly separate and partly overlapping constructs. The rehabilitation
      clients' motivational orientations were associated with their experiences and
      their perceptions on environmental factors and future possibilities, both those
      that precipitated the application for rehabilitation and those that are important
      in their current life situation and their perceived future possibilities.
      CONCLUSIONS: In the planning of individual rehabilitation processes there is a
      clear need to sort out what factors may hide behind the client's weak contextual
      or situational motivation. In the course of the rehabilitation process, it is
      important to discuss these factors in order to alleviate the clients' uncertainty
      towards change and enhance their motivation to participate in rehabilitation and
      re-think their future prospects of returning to work.

PMID- 24452472
TI  - beta-Arrestin1 and distinct CXCR4 structures are required for stromal derived
      factor-1 to downregulate CXCR4 cell-surface levels in neuroblastoma.
AB  - CXC chemokine receptor 4 (CXCR4) is a G protein-coupled receptor (GPCR) located
      on the cell surface that signals upon binding the chemokine stromal derived
      factor-1 (SDF-1; also called CXCL 12). CXCR4 promotes neuroblastoma proliferation
      and chemotaxis. CXCR4 expression negatively correlates with prognosis and drives
      neuroblastoma growth and metastasis in mouse models. All functions of CXCR4
      require its expression on the cell surface, yet the molecular mechanisms that
      regulate CXCR4 cell-surface levels in neuroblastoma are poorly understood. We
      characterized CXCR4 cell-surface regulation in the related SH-SY5Y and SK-N-SH
      human neuroblastoma cell lines. SDF-1 treatment caused rapid down-modulation of
      CXCR4 in SH-SY5Y cells. Pharmacologic activation of protein kinase C similarly
      reduced CXCR4, but via a distinct mechanism. Analysis of CXCR4 mutants delineated
      two CXCR4 regions required for SDF-1 treatment to decrease cell-surface CXCR4 in
      neuroblastoma cells: the isoleucine-leucine motif at residues 328 and 329 and
      residues 343-352. In contrast, and unlike CXCR4 regulation in other cell types,
      serines 324, 325, 338, and 339 were not required. Arrestin proteins can bind and
      regulate GPCR cell-surface expression, often functioning together with kinases
      such as G protein-coupled receptor kinase 2 (GRK2). Using SK-N-SH cells which are
      naturally deficient in beta-arrestin1, we showed that beta-arrestin1 is required
      for the CXCR4 343-352 region to modulate CXCR4 cell-surface expression following
      treatment with SDF-1. Moreover, GRK2 overexpression enhanced CXCR4
      internalization, via a mechanism requiring both beta-arrestin1 expression and the
      343-352 region. Together, these results characterize CXCR4 structural domains and
      beta-arrestin1 as critical regulators of CXCR4 cell-surface expression in
      neuroblastoma. beta-Arrestin1 levels may therefore influence the CXCR4-driven
      metastasis of neuroblastoma as well as prognosis. 

PMID- 24452476
TI  - The presence and impact of biofilm-producing staphylococci in atopic dermatitis.
AB  - IMPORTANCE: Atopic dermatitis (AD) is thought to be a double-hit phenomenon with
      an unknown environmental component and a genetic abnormality likely centered on
      the filaggrin gene. Biologically, the presence of Staphylococcus aureus in AD was
      reported more than 2 decades ago, but the relationship to AD has been elusive.
      OBJECTIVE: To explore the bacteria that produce the biofilms in the lesions of AD
      and the response of the innate immune system to these biofilm occlusions of the
      sweat ducts by specifically evaluating Toll-like receptor 2. DESIGN, SETTING, AND
      PARTICIPANTS: University hospital dermatologic clinic study involving the
      environmental component related to the characterization, correlation, and impact
      of staphylococci and their biofilms in AD. We processed routine skin swabs from
      lesional and nonlesional skin from 40 patients with AD and performed scrapings
      and biopsies. We also obtained 20 samples from controls (10 inflamed skin samples
      and 10 normal skin samples). EXPOSURES: Gram staining, bright-field microscopy,
      hematoxylin and eosin, periodic acid-Schiff, Congo red, and light microscopy.
      MAIN OUTCOMES AND MEASURES: Association of staphylococcal biofilms with AD
      pathogenesis. RESULTS: All AD-affected samples contained multidrug-resistant
      staphylococci, with S aureus (42.0%) and Staphylococcus epidermidis (20.0%) as
      the predominant species. All isolates were positive for extracellular
      polysaccharide and biofilm (85.0% strong biofilm producers and 15.0% moderately
      to weakly positive). Polymerase chain reaction revealed the biofilm-mediating
      icaD (93.0%) and aap (12.5%) genes in the isolates (some contained both). We also
      examined tissues for microbial identification, extracellular biomass formation,
      biofilm formation, and staphylococcal biofilm in skin tissues. Occlusion of sweat
      ducts with periodic acid-Schiff-positive and Congo red-positive material was
      noted on microscopic tissue examination. Toll-like receptor 2 was shown to be
      activated in AD lesional skin (immediately proximal to the sweat ducts), which
      likely led to the initiation of proteinase-activated receptor 2-mediated pruritus
      and MyD88-mediated spongiosis. CONCLUSIONS AND RELEVANCE: Biofilm formation by AD
      associated staphylococci almost certainly plays a major role in the occlusion of
      sweat ducts and leads to inflammation and pruritus. We believe the environmental
      hit in AD relates to staphylococci and their biofilms, which occlude sweat ducts.

PMID- 24452475
TI  - Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking
      activation of TLR4/MyD88-dependent pathway.
AB  - Paclitaxel, a known TLR4 ligand, leads to activation of TLR4/MyD88-dependent
      pathway that mediates chemoresistance and tumor progression in epithelial ovarian
      carcinoma (EOC). Atractylenolide-I (AO-I), a novel TLR4-antagonizing agent,
      inhibits TLR4 signaling by interfering with the binding of LPS or paclitaxel to
      membrane TLR4 of human leukocytes. In this study, AO-I was found to attenuate
      paclitaxel-induced protein expression of IL-6, VEGF and survivin, and to enhance
      early apoptosis and growth inhibition in MyD88(+) EOC cells; AO-I was shown to
      fit into the hydrophobic pocket of human MD-2 and to partially overlap with the
      binding site of paclitaxel by docking simulations, suggesting that AO-I may block
      the MD-2-mediated TLR4/MyD88-dependent paclitaxel signaling in MyD88(+) EOC
      cells. Therefore, AO-I could significantly sensitize the response of MyD88(+) EOC
      cells to paclitaxel by blocking MD-2-mediated TLR4/MyD88 signaling, and that AO-I
      paclitaxel combination could be a promising strategy for the treatment of EOC
      with a functional TLR4/MyD88/NF-kappaB pathway. 

PMID- 24452477
TI  - Long-standing type 1 diabetes: patients with adult-onset develop celiac-specific
      immunoreactivity more frequently than patients with childhood-onset diabetes, in
      a disease duration-dependent manner.
AB  - To assess the frequency of celiac-associated humoral autoimmunity in patients
      with long-standing childhood- and adult-onset type 1 diabetes (LDM1) and whether
      it occurs more frequently as the disease progresses. IgA-/IgG-anti-tissue
      transglutaminase (IgA-tTG and IgG-tTG) and IgA-/IgG-deamidated gliadin (DGP)
      antibodies were analyzed in 277 LDM1 sera (120 females; disease duration 19.3 +/-
      12.3 years, range 5.0-54.0 years). Of the 277 patients, 147 were childhood-onset
      LDM1 ((CH)LDM1) and 130 adult-onset LDM1 ((AD)LDM1); 6.1 % LDM1 sera were tTG-
      and/or DGP-antibody-positive, with a lower frequency among (CH)LDM1 as compared
      with (AD)LDM1 patients (3.4 vs 9.2 %, p = 0.048). Celiac-associated
      immunoreactivity was significantly more frequent in LDM1 with >15 years of
      disease duration (9.4 vs 2.9 % in those with <=15 years, p = 0.042) and among
      them in (AD)LDM1 (14.7 vs 4.2 % (CH)LDM1, p = 0.043). Celiac disease humoral
      immunoreactivity should be screened not only at diabetes onset, but also in long
      standing patients, especially adults with disease duration >15 years. 

PMID- 24452478
TI  - Differences in methylmercury and inorganic mercury biomagnification in a tropical
      marine food web.
AB  - Methylmercury (MeHg), inorganic mercury (Hginorg) and their biomagnification
      factors (BMF) were evaluated along a non-degraded Brazilian bay food web. Highly
      significant differences (p < 0.0001) were found between MeHg and Hginorg
      concentrations among all organisms (microplankton, shrimp, fish and dolphin).
      MeHg increased with increasing trophic position while Hginorg did not present the
      same pattern. BMF values for MeHg were higher than 1 for all trophic interactions
      from source to consumer, indicating that MeHg was transferred more efficiently
      and biomagnified over the entire web. Only one BMF exceeding one was observed for
      Hginorg (27) between microplankton and their consumer, planktivorous fish. BMF
      values for Hginorg were significantly different than those found for MeHg (20) at
      the base of the food web.

PMID- 24452479
TI  - Porous inorganic nanostructures with colloidal dimensions: synthesis and
      applications in electrochemical energy devices.
AB  - Porous inorganic nanostructures with colloidal dimensions can be considered as
      ideal components of electrochemical devices that operate on renewable energy
      sources. They combine nanoscale properties with good accessibility, a high number
      of active sites, short diffusion distances and good processability. Herein, we
      review some of the liquid-phase routes that lead to the controlled synthesis of
      these nanostructures in the form of non-hollow, hollow or yolk-shell
      configurations. From solar and fuel cells to batteries and supercapacitors, we
      put special emphasis on showing how these sophisticated structures can enhance
      the efficiency of electrochemical energy devices. 

PMID- 24452480
TI  - Diversification of EPR signatures in Site Directed Spin Labeling using a beta
      phosphorylated nitroxide.
AB  - Site Directed Spin Labeling (SDSL) combined with EPR spectroscopy is a very
      powerful approach to investigate structural transitions in proteins in particular
      flexible or even disordered ones. Conventional spin labels are based on nitroxide
      derivatives leading to classical 3-line spectra whose spectral shapes are
      indicative of the environment of the labels and thus constitute good reporters of
      structural modifications. However, the similarity of these spectral shapes
      precludes probing two regions of a protein or two partner proteins
      simultaneously. To overcome the limitation due to the weak diversity of nitroxide
      label EPR spectral shapes, we designed a new spin label based on a beta
      phosphorylated nitroxide giving 6-line spectra. This paper describes the
      synthesis of this new spin label, its grafting at four different positions of a
      model disordered protein able to undergo an induced alpha-helical folding and its
      characterization by EPR spectroscopy. For comparative purposes, a classical
      nitroxide has been grafted at the same positions of the model protein. The
      ability of the new label to report on structural transitions was evaluated by
      analyzing the spectral shape modifications induced either by the presence of a
      secondary structure stabilizer (trifluoroethanol) or by the presence of a partner
      protein. Taken together the results demonstrate that the new phosphorylated label
      gives a very distinguishable signature which is able to report from subtle to
      larger structural transitions, as efficiently as the classical spin label. As a
      complementary approach, molecular dynamics (MD) calculations were performed to
      gain further insights into the binding process between the labeled NTAIL and PXD.
      MD calculations revealed that the new label does not disturb the interaction
      between the two partner proteins and reinforced the conclusion on its ability to
      probe different local environments in a protein. Taken together this study
      represents an important step forward in the extension of the panoply of SDSL-EPR
      approaches. 

PMID- 24452483
TI  - Complexation of metal carbonyl units with [alpha-PW11O39]7- and [alpha2
      P2W17O61]10-: insights into the chiral "twisted-sandwich" dimeric structures.
AB  - Several polyoxometalate-supported metal carbonyl complexes,
      K7Na3P2W23O80{Re(CO)3}2.38H2O (1), (C3H10N)8Na2P2W23O80{Re(CO)3}2.10H2O (1a) and
      (C3H10N)6KNa3P2W23O80{Mn(CO)3}2.7H2O (2), have been prepared from the
      dimerization of the monovacant Keggin [alpha-PW11O39](7-) with metal carbonyl
      complexes [M(CO)3](+) (M = Re, Mn) in acidic aqueous solutions. The resulting
      "twisted-sandwich" architectures are chiral, but their crystalline solids are
      racemic. A detailed investigation involving syntheses, crystal structures, and
      electrochemistry is presented.

PMID- 24452481
TI  - Cause and outcome of cerebellar mutism: evidence from a systematic review.
AB  - PURPOSE: Cerebellar mutism is a serious neurosurgical complication after
      posterior fossa surgery, but the cause, incidence and outcome remain incompletely
      defined. The aim of this paper was to identify and review all reports of this
      phenomenon to better delineate and improve the evidence base. METHODS: A
      systematic search and retrieval of databases was conducted using advanced search
      techniques. Review/outcomes criteria were developed, and study quality was
      determined. RESULTS: The retrieval identified 2,281 papers of which 96 were
      relevant, identifying 650 children with cerebellar mutism. Causative factors,
      clinical features and outcomes were reported variably; papers focussed on
      multiple areas, the majority reporting incidence in single or series of case
      studies with little or no analysis further than description. CONCLUSIONS: The
      complexity and variability of data reporting, likely contributing factors and
      outcomes make cerebellar mutism difficult to predict in incidence and the degree
      of impact that may ensue. A clear and accepted universal definition would help
      improve reporting, as would the application of agreed outcome measures. Clear and
      consistent reporting of surgical technique remains absent. Recommendations for
      practice are provided.

PMID- 24452482
TI  - Ten-year follow-up of a prospective trial for the targeted therapy of gastric
      cancer with the human monoclonal antibody PAT-SC1.
AB  - The fully human monoclonal antibody PAT-SC1 is specific for an isoform of CD55
      (decay-accelerating factor) designated CD55PAT-SC1. This antigen is expressed in
      the majority (80%) of gastric cancers (GCs), and the antibody induces tumour cell
      specific apoptosis in vitro as well as in vivo. PAT-SC1, therefore, has been
      deemed promising as a therapeutic agent. Here, we describe the results of an
      academic clinical study performed in a neoadjuvant setting with resectable GC
      patients. Patients undergoing treatment for GC between 1997 and 2001 were tested
      for CD55PAT-SC1 expression. Fifty-one resectable patients that tested positively
      received a single administration of 20 mg PAT-SC1 48 h prior to surgery. They
      underwent standard surgery with either subtotal or total gastrectomy with
      bursectomy, omentectomy and a modified D2-lymphadenectomy, aimed at R0 resection.
      Primary endpoints of the present study were to evaluate side-effects of the PAT
      SC1 antibody treatment and to evaluate histopathological effects such as tumour
      regression and induction of apoptosis. Long-term survival was a secondary
      endpoint. Administration of PAT-SC1 appeared safe with only reversible side
      effects according to WHO grade I and II. Despite the low-dose of the antibody,
      81.6% of the patients showed signs of increased apoptosis within the primary
      tumour and 60% showed signs of tumour cell regression. Comparison of the 10-year
      survival rates of the R0-resected CD55PAT-SC1-positive patients treated with the
      PAT-SC1 antibody with a historical collective of R0-resected CD55PAT-SC1-positive
      patients not treated with PAT-SC1 indicated a survival benefit in the treated
      patients. Furthermore, comparison of the patient survival of CD55PAT-SC1-positive
      vs. CD55PAT-SC1-negative groups suggested that CD55PAT-SC1 antigen expression is
      an independent predictor of poor survival in a Cox regression analysis. Antibody
      PAT-SC1 may be a useful additive therapeutic agent in the treatment of patients
      with CD55PAT-SC1-expressing GCs. In combination with radical standard surgery,
      PAT-SC1 given as an adjuvant or neoadjuvant immunotherapeutic agent induces
      apoptosis in tumour cells which may improve survival of these patients. Because
      of the human origin and its specific binding to the CD55PAT-SC1 antigen, PAT-SC1
      was well tolerated in this trial.

PMID- 24452484
TI  - Efficacy and safety of secukinumab in chronic plaque psoriasis and psoriatic
      arthritis therapy.
AB  - Psoriasis is a chronic inflammatory skin disease affecting about 1-3% of the
      general population. Moderate-to-severe psoriasis is commonly associated with
      various comorbidities, including psoriatic arthritis (PsA) and cardio-metabolic
      disorders such as obesity, hypertension, diabetes, and metabolic syndrome. There
      is increasing recognition that systemic inflammation accompanies severe skin
      disease. Abnormal innate and adaptive immune responses in the skin are involved
      in pathogenesis. The cytokine interleukin (IL)-17A is produced by T helper 17
      (Th17) cells, neutrophils, mast cells, and T cytotoxic 17 cells. IL-17 plays a
      key role in host defense against extracellular bacteria and fungi. IL-17A acts on
      keratinocytes to increase expression of chemokines involved in recruiting myeloid
      dendritic cells, Th17 cells, and neutrophils to the lesion site. IL-17A also
      induces the production of antimicrobial peptides and pro-inflammatory cytokines
      that, in turn, may amplify and sustain immune responses in the skin. Blocking IL
      17A improved psoriasis-like pathology in experimental models, and reduction in IL
      17 signaling is part of the mechanism of action of tumor necrosis factor-alpha
      blockers. Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or
      antagonizing its receptor (i.e., brodalumab) are currently being tested for
      efficacy and safety in the treatment of plaque psoriasis and PsA. Secukinumab is
      a fully human IgG1 monoclonal antibody that selectively binds and neutralizes IL
      17A whose efficacy in the therapy of chronic plaque psoriasis has been
      demonstrated in different phase II clinical trial. No new safety signals have
      emerged so far. 

PMID- 24452485
TI  - Correlation of low expression of hMOF with clinicopathological features of
      colorectal carcinoma, gastric cancer and renal cell carcinoma.
AB  - Human MOF (males absent on the first), as a histone acetyltransferase, is
      responsible for histone H4K16 acetylation in human cells. Recent studies have
      shown that the abnormal gene expression of hMOF is involved in certain primary
      cancers. Here, we first report the involvement of hMOF expression in clinically
      diagnosed primary colorectal carcinoma (CRC) and gastric cancer. Simultaneously,
      the correlation of hMOF expression and clinicopathological features in CRC,
      gastric cancer and renal cell carcinoma (RCC) was analyzed. The hMOF mRNA
      expression was assessed in 44 CRC, 16 gastric cancer and 47 RCC human tissue
      samples by quantitative PCR (qPCR). Statistical analysis of qPCR data revealed a
      significant reduction (>2-fold decrease) of hMOF gene expression in CRC, 57%
      (25/44), 94% (15/16) in gastric cancer and 74% (35/47) in RCC tissues of the
      patients. In patients with CRC, lymph node metastasis and tumor stage were
      associated with hMOF expression patterns. However, no significant association
      between hMOF expression and tumor types emerged (p>0.05). Interestingly, in
      patients with gastric cancer, although no statistically significant difference
      was found between adjacent (<2 cm away from the cancer tissue) and normal tissues
      (>5 cm away from the cancer tissue), >2-fold reduction of hMOF expression in
      adjacent tissues had already appeared in 35% of patients. In addition, low
      expression of hMOF was strongly correlated with tumor differentiation (p<0.05)
      and survival of patients with gastric cancer (p<0.001). While in patients with
      RCC, downregulation of hMOF was connected to ccRCC and tissues with T1 tumor
      status. Our results suggest that downregulation of hMOF may be common in cancer
      tissues, and may represent a novel biomarker for tumor diagnosis.

PMID- 24452486
TI  - A qualitative investigation of the effects of psycho-spiritual integrative
      therapy on breast cancer survivors' experience of paradox.
AB  - This study is an exploratory, qualitative investigation of breast cancer
      survivors' experiences of paradox, following psycho-spiritual integrative therapy
      (PSIT). Previous studies examined the role of paradox in spiritual development
      among women diagnosed with cancer; this study investigated a psycho-spiritual
      intervention for multicultural cancer survivors. Twelve multicultural breast
      cancer survivors, from a sample of 30 women participants in an 8-week PSIT group
      intervention, were recruited from oncologists, hospitals, support groups,
      outpatient oncology centers, surgeons, radiation therapy centers, cancer events,
      and websites. We conducted semi-structured, open-ended interviews lasting 1-2 h
      regarding participants' experiences coping with cancer and their experience of
      PSIT. We transcribed interviews and conducted blind searches for both new and
      previously identified paradoxes and themes. Two previously identified themes
      emerged: (1) attempting to maintain coherence in new and old ways and (2) letting
      go of ultimate control in life. Additionally, three novel themes emerged: (1)
      interconnection between helpers and hinderers, (2) spiritual edges and tensions,
      and (3) new paths to empowerment. Results of this qualitative analysis indicate
      participants experienced previously identified themes and experienced an expanded
      range of paradoxes. After learning compassionate acceptance through PSIT, breast
      cancer survivors develop greater access to the multidimensionality of paradoxes,
      which can go beyond a binary (either/or) construction to a more interdependent
      (both/and) relationship. Devoting greater attention to investigating and
      understanding how diverse participants engage with and move through paradoxical
      change processes could enhance the effectiveness of existential and spiritual
      interventions. 

PMID- 24452487
TI  - The role of attention problems and impulsiveness in media violence effects on
      aggression.
AB  - Previous research has established media violence as a causal risk factor for
      aggressive behavior. Several theoretical mechanisms have been identified to
      explain this effect. The present study assessed 422 undergraduate students to
      test the possibility that individual differences in attention problems and
      impulsiveness can help explain the link between violent media and aggression.
      Attention problems and impulsiveness proved to be a distinct construct from other
      processes believed to mediate aggression (aggressive beliefs, aggression related
      schemata, trait anger, and trait hostility). Attention problems and impulsiveness
      were uniquely related to both media exposure (total weekly hours and violent
      content) and aggression. Attention problems and impulsiveness were particularly
      related to impulsive (as opposed to premeditated) aggression. These results
      suggest that attention problems and impulsiveness may play an important role in
      violent media effects on aggression.

PMID- 24452488
TI  - Objectifying research on special region corresponding to five internal organs in
      colour inspections of Chinese medicine.
AB  - OBJECTIVE: To study the differences in a special region (SR) corresponding to
      five internal organs between the young and the elderly and to verify the
      effectiveness of a developed system for objectifying research in colour
      inspections of Chinese medicine (CICM). METHODS: An image acquisition device
      imitating daylight to meet the requirement of CICM was designed. Image processing
      software based on CICM theory was developed. A total of 83 normal people were
      sampled and assigned to two groups. The first group (Group I) included 30 people
      with an average age of 24+/-2, and the second group (Group II) included 53 people
      with an average age of 74+/-4. After image processing, the chromaticity of 10 SRs
      corresponding to five internal organs was calculated. R, G, and B represent the
      chromaticity of color red, green, and blue, L indicates color brightness, whereas
      a and b denote red and yellow respectively. The difference between the young and
      the elderly was analyzed. RESULTS: (1) The chromaticity of each SR corresponding
      to five organs was obtained. The average R, G, B, L, a, and b of the sample were
      194.4, 147.6, 119.3, 65.2, 15.5, and 22.3, respectively. (2) The R, G, B, and L
      of the young were greater than those of the elderly, but the a and b of the young
      were less than those of the elderly. (3) A statistically significant difference
      in each SR was found between the young and the elderly (P <0.05). The total
      differences for the Lung (Fei), Heart (Xin), Liver (Gan), Spleen (Pi), and Kidney
      (Shen) were 50% (3/6), 66.7% (4/6), 66.7% (4/6), 83.3% (5/6), and 91.7% (33/36),
      respectively. However, the Kidney SR had the greatest statistical discrepancy.
      CONCLUSION: The old Chinese saying that human Kidney deficiency worsens with age
      was verified by the results. The objectifying system used to examine CICM was
      effective. Thus, this system may be used as a basis for further research.

PMID- 24452490
TI  - Use of evidence-based pharmacotherapy for secondary prevention of coronary heart
      disease: a Chinese medicine hospital versus a general hospital.
AB  - OBJECTIVE: To determine differences in adherence to secondary prevention
      guidelines (pharmacological interventions) among coronary heart disease (CHD)
      patients between a Chinese medicine (CM) hospital and a general hospital in a
      Chinese city. METHODS: Medical records of 200 patients consecutively discharged
      from the CM hospital and the general hospital for CHD were reviewed to determine
      the proportions of eligible patients who received antiplatelet agents, beta
      blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor
      blockers (ARBs) and statins at discharge. The effects of patient characteristics
      and hospital type on the use of these medicines were estimated using logistic
      regression models. RESULTS: Patients discharged from the CM hospitals were older;
      more likely females; had greater history of hyperlipidemia, cerebrovascular
      diseases and less smoker (P<0.01 or P<0.05). They were less likely to receive
      coronary angiography and percutaneous coronary intervention, and had a longer
      length of stay than those discharged from the general hospital (P<0.01 or
      P<0.05). There were no significant differences in antiplatelet agents (96% vs.
      100%, P=0.121) or statins (97.9% vs. 100%, P=0.149) use between the CM hospital
      and the general hospital. In multivariable analyses that adjusted for patient
      characteristics and hospital type, there was no significant difference in use of
      beta-blockers between the CM hospital and the general hospital. In contrast,
      patients discharged from the CM hospital were less likely to receive ACE
      inhibitors/ARBs compared with those discharged from the general hospital (odds
      ratio: 0.3, 95% confidence interval: 0.105-0.854). CONCLUSION: In this study, the
      CM hospital provides the same quality of care in CHD for prescribing evidence
      based medications at discharge compared with another general hospital except for
      ACE inhibitors/ARBs use.

PMID- 24452492
TI  - HR 3 Tesla MRI for the diagnosis of endolymphatic hydrops and differential
      diagnosis of inner ear tumors--demonstrated by two cases with similar symptoms.
AB  - The synchronous appearance of different inner ear pathologies with a nearly
      equivalent clinical manifestation such as Meniere's disease and vestibular
      schwannoma is very rare but leads to a relevant dilemma concerning therapy
      options. MRI is the method of choice to detect intralabyrinthine tumors. Since
      endolymphatic hydrops is considered the morphological equivalent of Meniere's
      disease, magnetic resonance imaging including hT2w-FLAIR sequences 4 h after i.
      v. administration of gadolinium-based contrast agents (GBCA) allows the diagnosis
      and grading of endolymphatic hydrops in vivo synchronous to diagnosis and
      monitoring of ILT. To this day, only a few cases of intralabyrinthine schwannoma
      could be shown to appear simultaneously with endolymphatic hydrops by MRI, but to
      our knowledge the dedicated distinction of endolymphatic space has not been
      previously demonstrated. The aim of this work was not only to detect the
      coincidence of endolymphatic hydrops and vestibular schwannoma, but also to
      differentiate tumor tissue from endolymphatic space by 3 Tesla MRI. This enables
      therapy options that are originally indicated for Meniere's disease. The aim of
      this work was to describe the feasibility and usefulness of endolymphatic hydrops
      MRI on intralabyrinthal tumors in a special case of intravestibular schwannoma to
      demonstrate the high clinical relevance and impact in therapeutic decision-making
      for the synchronous appearance of endolymphatic hydrops and intralabyrinthine
      tumors. Therefore, we present a typical case of Meniere's disease in contrast to
      a patient with an intralabyrinthine schwannoma and Meniere-like symptoms.

PMID- 24452489
TI  - Changes of neuronal acetylcholine receptor alpha 7 of peritoneal macrophage in
      experimental acute pancreatitis treated by Chaiqin Chengqi Decoction ().
AB  - OBJECTIVE: To investigate effect of Chaiqin Chengqi Decoction (, CQCQD) on
      changes of neuronal acetylcholine receptor alpha 7 (nAChRalpha7) of peritoneal
      macrophages in acute pancreatitis (AP). METHODS: Eighteen Kunming mice were
      equally randomized into the control group, AP group and CQCQD treatment group. AP
      was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart,
      while control mice received saline injections. At 72 h after the first injection
      of L-arginine, mice in the treatment group were intragastrically administered 0.1
      mL/10 g CQCQD every 2 h for 3 times, whilst mice in the other two groups received
      the same amount of saline feeding. Mice were sacrificed by cervical dislocation 2
      h after the last feeding of either CQCQD or saline. Peritoneal macrophages were
      collected for determination of nAChRalpha7 mRNA and protein expression. Serum was
      collected for detection of interleukin-6 (IL-6), IL-10 and acetylcholine (ACh)
      levels, and pancreas was for histopathology analysis. RESULTS: The CQCQD
      treatment significantly ameliorated the severity of AP as evidenced by reducing
      the pancreatic histopathology score (4.5+/-0.5 vs. 6.2+/-1.7, P<0.05) and the
      serum IL-6 levels (1228.3+/-419.2 pg/mL vs. 1589.6+/-337.3 pg/mL, P<0.05). The
      mRNA and protein expression of nAChRalpha7 of the peritoneal macrophages in the
      AP group were similar to the control group (P>0.05), but were significantly up
      regulated after the CQCQD treatment (P<0.05). The serum ACh levels in the AP
      group were significantly lower than those in the control group (3.1+/-0.6 MUg/mL
      vs 4.8+/-0.7 MUg/mL P<0.05), but were significantly increased after the CQCQD
      treatment (5.6+/-1.5 MUg/mL vs 3.1+/-0.6 MUg/mL, P<0.05). CONCLUSION: CQCQD is
      protective against L-arginine-induced AP through mechanisms involving nAChRalpha7
      of peritoneal macrophages.

PMID- 24452493
TI  - Multiparametric magnetic resonance imaging in the detection of prostate cancer.
AB  - Prostate cancer is the most common malignancy in men, but only about 10 % of
      patients die from that cancer. Recent studies suggest that not all patients
      benefit from a radical therapeutic approach. When prostate cancer is suspected,
      magnetic resonance imaging (MRI) can make an important contribution to cancer
      localization within the prostate. Many studies show that T2-weighted morphologic
      imaging should be supplemented by multiparametric MRI techniques including
      diffusion-weighted imaging, contrast-enhanced sequences, and MR spectroscopy.
      This approach detects aggressive prostate cancer with high sensitivity and
      specificity. The findings of multiparametric MRI additionally contribute
      information to the assessment of cancer aggressiveness. The use of these
      multiparametric MRI techniques will gain an increasing role in the clinical
      management of prostate cancer patients. They can help in establishing a
      definitive diagnosis with a minimum of invasiveness and may also contribute to
      optimal individualized treatment. This review article presents the different
      techniques of multiparametric MRI and discusses their contribution to the
      detection of prostate cancer. Moreover, this review outlines an objective
      approach to image interpretation and structured reporting of MRI findings using
      the PI-RADS criteria. The review concludes with an outline of approaches to
      prostate biopsy on the basis of MRI (transrectal ultrasound, direct MRI guidance
      of tissue sampling, and MRI-ultrasound fusion biopsy) and emerging future uses of
      MRI in the planning of focal treatment options and in the active surveillance of
      patients diagnosed with prostate cancer.

PMID- 24452494
TI  - 'Click cyclic ADP-ribose': a neutral second messenger mimic.
AB  - Analogues of the potent Ca(2+) releasing second messenger cyclic ADP-ribose
      (cADPR) with a 1,2,3-triazole pyrophosphate bioisostere were synthesised by click
      mediated macrocyclisation. The ability to activate Ca(2+) release was
      surprisingly retained, and hydrolysis of cADPR by CD38 could also be inhibited,
      illustrating the potential of this approach to design drug-like signalling
      pathway modulators. 

PMID- 24452495
TI  - Correction of hemostatic abnormalities and portal pressure variations in patients
      with cirrhosis.

PMID- 24452496
TI  - Condoms used but sex not well protected.
AB  - Condom use is often equated to safer sex. The prevalence of condom use during sex
      work among female sex workers (FSW) in China is high. Condom use, however, co
      exists with condom failure and improper use and hence risk of HIV transmission.
      In a cross-sectional study, we interviewed 195 FSW in Shenzhen, China. The
      prevalence of condom use in the last episode of sex work was 97.4 %, However,
      respectively 53.8 and 86.2 % had experienced at least one condition of condom
      failure that may lead to genital contact (wearing condoms after penetration,
      condom breakage/slippage, condoms removed by clients) and at least one condition
      of improper condom use (not removing air from the tip of the condom, not pulling
      it down to the root of penis and not choosing good quality condoms). Factors of
      individual level (e.g. never choosing high quality condoms for sex work), inter
      personal level (e.g. agreement to have unprotected sex if fond of clients or paid
      more) and environmental/structural level (e.g. non-availability of condoms) were
      associated with various types of condom failure and improper use. Although HIV
      prevention interventions have increased prevalence of condom use among FSW, the
      risk of HIV transmission may still be high as "unsafe" sex due to condom failure
      and improper use is prevalent. Interventions promoting safer sex need to address
      such issues and take socio-ecological factors into account. Condom use during sex
      work is not equivalent to well protected sex as the protective effects could be
      compromised by frequent condom failure and improper use.

PMID- 24452498
TI  - Effectiveness of HIV prevention for women: what is working?
AB  - The HIV-AIDS remains a public health problem which disproportionally affects
      women. However, prevention strategies have rarely considered their specific
      efficacy for them. For this reason, this study examines the differential
      effectiveness of six intervention elements based on socio-cognitive theories
      addressing young women. A controlled between-groups design examined the change in
      risk profile among 167 young Spanish women (mean age 21.3 years old) involved in
      five sexual risk prevention interventions (informative talk, attitudinal
      discussion, role-play, fear induction and informative website) and one control
      non-intervening group (waiting list). Our findings support the differential
      efficacy of some HIV preventive intervention elements comparing others for women.
      In particular, the attitudinal discussion stands out followed by the informative
      talk and the role play. Contrarily, the fear induction component did not reveal
      relevant improvements. This study provides new evidence related to HIV
      prevention. Particularly, the higher efficacy of motivational components for
      these young Spanish women is revealed.

PMID- 24452497
TI  - The validity of the Substance Abuse and Mental Illness Symptom Screener (SAMISS)
      in people living with HIV/AIDS in primary HIV care in Cape Town, South Africa.
AB  - Given the high prevalence of HIV in South Africa and co-morbid mental disorders
      in people living with HIV/AIDs (PLWHA) we sought to validate a brief screening
      tool in primary HIV care. METHODS: 366 PLWHA were recruited prior to combination
      anti-retroviral treatment (CART) initiation from two primary health HIV clinics.
      A mental health nurse administered a socio-demographic questionnaire and the Mini
      Neuropsychiatric Interview (MINI) and a lay counsellor administered the Substance
      and Mental Illness Symptom Screener (SAMISS). RESULTS: Using the MINI, 17 % of
      participants were identified with either depression, anxiety disorders or
      adjustment disorder and 18 % with substance or alcohol abuse/dependence. The
      sensitivity and specificity of the SAMISS was 94 % (95 % CI: 88-98 %) and 58 %
      (95 % CI: 52-65 %) respectively, with the alcohol component (sensitivity: 94 %;
      specificity: 85 %) performing better than the mental illness component of the
      SAMISS (sensitivity: 97 %; specificity: 60 %). The specificity of the tool
      improved when the cut-off for the mental illness component was increased.
      CONCLUSION: The SAMISS may provide a useful first tier screening tool for common
      mental disorders in primary care for PLWHA.

PMID- 24452499
TI  - Advances in metered dose inhaler technology: formulation development.
AB  - Pressurized metered dose inhalers (MDIs) are a long-standing method to treat
      diseases of the lung, such as asthma and chronic obstructive pulmonary disease.
      MDIs rely on the driving force of the propellant, which comprises the bulk of the
      MDI formulation, to atomize droplets containing drug and excipients, which
      ideally should deposit in the lungs. During the phase out of chlorofluorocarbon
      propellants and the introduction of more environmentally friendly
      hydrofluoroalkane propellants, many improvements were made to the methods of
      formulating for MDI drug delivery along with a greater understanding of
      formulation variables on product performance. This review presents a survey of
      challenges associated with formulating MDIs as solution or suspension products
      with one or more drugs, while considering the physicochemical properties of
      various excipients and how the addition of these excipients may impact overall
      product performance of the MDI. Propellants, volatile and nonvolatile cosolvents,
      surfactants, polymers, suspension stabilizers, and bulking agents are among the
      variety of excipients discussed in this review article. Furthermore, other
      formulation approaches, such as engineered excipient and drug-excipient
      particles, to deliver multiple drugs from a single MDI are also evaluated. 

PMID- 24452500
TI  - Self-nanoemulsifying drug delivery system of nifedipine: impact of hydrophilic
      lipophilic balance and molecular structure of mixed surfactants.
AB  - A simple but novel mixed surfactant system was designed to fabricate a self
      nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic
      balance (HLB) value. The impacts of HLB and molecular structure of surfactants on
      the formation of SNEDDS were investigated. After screening various oils and
      surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with
      Imwitor((r)) 742 as oil and Tween((r))/Span((r)) or Cremophor((r))/Span((r)) as
      mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS
      containing Tween((r))/Span((r)) in aqueous medium was independent of the HLB of a
      mixed surfactant. The use of the Cremophor((r))/Span((r)) blend gave nanosized
      emulsion at higher HLB. The structure of the surfactant was found to influence
      the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded
      liquid SNEDDS comprising Cremophor((r)) RH40/Span((r)) 80 onto Aerosil((r)) 200
      or Aerosil((r)) R972 as inert solid carrier. Solid SNEDDS formulations using
      higher amounts (30-50% w/w) of Aerosil((r)) 200 exhibited good flow properties
      with smooth surface and preserved the self-emulsifying properties of liquid
      SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid
      SNEDDS revealed the transformation of the crystalline structure of NDP due to its
      molecular dispersion state. In vitro dissolution study demonstrated higher
      dissolution of NDP from solid SNEDDS compared with NDP powder. 

PMID- 24452501
TI  - Engineering topological surface states and giant Rashba spin splitting in
      BiTeI/Bi2Te3 heterostructures.
AB  - The search for strongly inversion asymmetric topological insulators is an active
      research field because these materials possess distinct properties compared with
      the inversion symmetric ones. In particular, it is desirable to realize a large
      Rashba spin-splitting (RSS) in such materials, which combined with the
      topological surface states (TSS) could lead to useful spintronics applications.
      In this report, based on first principles calculations, we predict that the
      heterostructure of BiTeI/Bi2Te3 is a strong topological insulator with a giant
      RSS. The coexistence of TSS and RSS in the current system is native and stable.
      More importantly, we find that both the Z2 invariants and the Rashba energy can
      be controlled by engineering the layer geometries of the heterostructure, and the
      Rashba energy can be made even larger than that of bulk BiTeI. Our work opens a
      new route for designing topological spintronics devices based on inversion
      asymmetric heterostructures.

PMID- 24452503
TI  - Catalysis and molecular magnetism of dinuclear iron(III) complexes with N-(2
      pyridylmethyl)-iminodiethanol/-ate.
AB  - The reaction of N-(2-pyridylmethyl)iminodiethanol (H2pmide) and Fe(NO3)3.9H2O in
      MeOH led to the formation of a dimeric iron(III) complex,
      [(Hpmide)Fe(NO3)]2(NO3)2.2CH3OH (1). Its anion-exchanged form, [(pmide)Fe(N3)]2
      (2), was prepared by the reaction of 1and NaN3 in MeOH, during which the Hpmide
      ligand of 1 was also deprotonated. These compounds were investigated by single
      crystal X-ray diffraction and magnetochemistry. In complex 1, one iron(III) ion
      was bonded with a mono-deprotonated Hpmide ligand and a nitrate ion. The two
      iron(III) ions within the dinuclear unit were connected by two ethoxy groups with
      an inversion center. In 2, one iron(III) ion was coordinated with a deprotonated
      pmide ligand and an azide ion. The Fe(pmide)(N3) unit was related by symmetry
      through an inversion center. Both 1 and 2 efficiently catalyzed the oxidation of
      a variety of alcohols under mild conditions. The oxidation mechanism was proposed
      to involve an Fe(IV)=O intermediate as the major reactive species and an Fe(V)=O
      intermediate as a minor oxidant. Evidence for this proposal was derived from
      reactivity and Hammett studies, KIE (kH/kD) values, and the use of MPPH (2-methyl
      1-phenylprop-2-yl hydroperoxide) as a mechanistic probe. Both compounds had
      significant antiferromagnetic interactions between the iron(III) ions via the
      oxygen atoms. 1 showed a strong antiferromagnetic interaction within the Fe(III)
      dimer, while 2 had a weak antiferromagnetic coupling within the Fe(III) dimer.

PMID- 24452502
TI  - Clinical and MRI evaluation of medium- to long-term results after autologous
      osteochondral transplantation (OCT) in the knee joint.
AB  - PURPOSE: Autologous osteochondral transplantation (OCT) is one of the surgical
      options currently used to treat cartilage defects. It is the only cartilage
      repair method that leads to a transfer of hyaline cartilage repair tissue. The
      purpose of this study was to evaluate the magnetic resonance observation of
      cartilage repair tissue (MOCART) score, the 3D MOCART score and various clinical
      scores in patients after OCT in knee joints. METHODS: Two women and eight men
      were evaluated 6-9 years (median 7.2 years) after OCT on the femoral condyle of
      the knee joint. All patients were evaluated by magnetic resonance imaging (MRI)
      measurement, using a 3.0 T Scanner with different cartilage-specific sequences.
      Clinical assessment included the knee injury and osteoarthritis outcome score
      (KOOS), the international knee documentation committee (IKDC) subjective knee
      form, the Noyes sport activity rating scale and the Tegner activity score. For
      MRI evaluation, the MOCART score and 3D MOCART score were applied. RESULTS:
      Clinical long-term results after OCT showed median values of 77 (range 35.7-71.4)
      for the IKDC; 50 (6.3-100), 66.7 (30.6-97.2), 65 (0-75), 57.1 (35.7-71.4) and
      80.9 (30.9-100) for the KOOS subscales (quality of life, pain sports, symptoms
      and activity of daily living); 61.4 (22.3-86.2) for the Noyes scale; and 3 (0-6)
      for the Tegner activity score. The median MOCART score was 75 (30-90) after both
      1 and 2 years and 57.5 (35-90) after 7 years, as assessed by different cartilage
      specific sequences. The 3D MOCART score showed values of 70 (50-85) and 60 (50
      80) in the two different isotropic sequences after 7 years. CONCLUSION: The
      MOCART and 3D MOCART scores are applicable tools for patient follow-up after OCT.
      Post-operative follow-up assessments would also benefit from the inclusion of OCT
      specific parameters. Long-term results after OCT reflect an impairment in
      clinical scores in the first 2 years with good results during follow-up. Stable
      conditions were observed between 2 and 7 years after surgery. The filling of the
      defects and the cartilage interface appeared good at MRI evaluation after the
      first 2 years, but cartilage loss was observed between the medium- and long-term
      follow-ups. Isotropic imaging with multiplanar reconstruction is useful for daily
      clinical use to assess bony cylinders in cartilage repair, especially in
      combination with the 3D MOCART. LEVEL OF EVIDENCE: Retrospective therapeutic
      study, Level IV.

PMID- 24452504
TI  - Potential impact of DSM-5 criteria on autism spectrum disorder prevalence
      estimates.
AB  - IMPORTANCE: The DSM-5 contains revised diagnostic criteria for autism spectrum
      disorder (ASD) from the DSM-IV-TR. Potential impacts of the new criteria on ASD
      prevalence are unclear. OBJECTIVE: To assess potential effects of the DSM-5 ASD
      criteria on ASD prevalence estimation by retrospectively applying the new
      criteria to population-based surveillance data collected for previous ASD
      prevalence estimation. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional,
      population-based ASD surveillance based on clinician review of coded behaviors
      documented in children's medical and educational evaluations from 14
      geographically defined areas in the United States participating in the Autism and
      Developmental Disabilities Monitoring (ADDM) Network in 2006 and 2008. This study
      included 8-year-old children living in ADDM Network study areas in 2006 or 2008,
      including 644 883 children under surveillance, of whom 6577 met surveillance ASD
      case status based on the DSM-IV-TR. MAIN OUTCOMES AND MEASURES: Proportion of
      children meeting ADDM Network ASD criteria based on the DSM-IV-TR who also met
      DSM-5 criteria; overall prevalence of ASD using DSM-5 criteria. RESULTS: Among
      the 6577 children classified by the ADDM Network as having ASD based on the DSM
      IV-TR, 5339 (81.2%) met DSM-5 ASD criteria. This percentage was similar for boys
      and girls but higher for those with than without intellectual disability (86.6%
      and 72.5%, respectively; P < .001). A total of 304 children met DSM-5 ASD
      criteria but not current ADDM Network ASD case status. Based on these findings,
      ASD prevalence per 1000 for 2008 would have been 10.0 (95% CI, 9.6-10.3) using
      DSM-5 criteria compared with the reported prevalence based on DSM-IV-TR criteria
      of 11.3 (95% CI, 11.0-11.7). CONCLUSIONS AND RELEVANCE: Autism spectrum disorder
      prevalence estimates will likely be lower under DSM-5 than under DSM-IV-TR
      diagnostic criteria, although this effect could be tempered by future adaptation
      of diagnostic practices and documentation of behaviors to fit the new criteria.

PMID- 24452505
TI  - Impact of long-term exposure to sodium arsenite on cytogenetic radiation damage.
AB  - The aim of this work was to investigate the impact of long-term exposure to low
      concentrations of sodium arsenite on the cellular response to ionising radiation.
      Human lymphoblastoid GM1899a cells were cultured in the presence of sodium
      arsenite for up to six months. Following chemical exposure, acute challenge doses
      of X-rays were given and chromosome damage (dicentrics, acentric fragments,
      translocations, micronuclei) as well as cell growth and changes in cell cycle
      kinetics were determined. Initial short-term chemical exposures determined 8
      ng/ml (60 nM) sodium arsenite as a suitable concentration for chronic exposures,
      which is below the current World Health Organization limit for arsenic in
      drinking water. At this concentration, cell growth was slightly, but
      consistently, slower than in untreated cultures throughout the six-month exposure
      period. Long-term exposure to the chemical induced no dicentrics and did not
      significantly alter the yield of dicentrics induced by 1 Gy acute X-irradiation.
      Similar results were obtained for chromosome translocations. In contrast,
      exposure to 8 ng/ml sodium arsenite induced significant levels of acentric
      fragments and micronuclei. Fragment/micronuclei data in combined treatment
      samples compared with single treatments were consistent with an additive effect
      of chemical and radiation exposure. As for X-rays, micronuclei induced by sodium
      arsenite tended to show no centromere in situ hybridisation signal, indicating
      that they represent structural aberrations rather than mis-segregated
      chromosomes. Similar results were obtained in human peripheral lymphocytes
      following short-term exposure to sodium arsenite or X-rays. Overall, an additive
      effect was observed for all combined exposures. Cellular radiation responses
      therefore seem to operate without any modulatory effects from chronic low level
      exposure to sodium arsenite in the systems analysed here.

PMID- 24452506
TI  - Intracellular galectins in cancer cells: potential new targets for therapy
      (Review).
AB  - Dysregulation of galectin expression is frequently observed in cancer tissues.
      Such an abnormal expression pattern often correlates with aggressiveness and
      relapse in many types of cancer. Because galectins have the ability to modulate
      functions that are important for cell survival, migration and metastasis, they
      also represent attractive targets for cancer therapy. This has been well
      exploited for extracellular galectins, which bind glycoconjugates expressed on
      the surface of cancer cells. Although the existence of intracellular functions of
      galectins has been known for many years, an increasing number of studies indicate
      that these proteins can also alter tumor progression through their interaction
      with intracellular ligands. In fact, in some instances, the interactions of
      galectins with their intracellular ligands seem to occur independently of their
      carbohydrate recognition domain. Such findings call for a change in the basic
      assumptions, or paradigms, concerning the activity of galectins in cancer and may
      force us to revisit our strategies to develop galectin antagonists for the
      treatment of cancer. 

PMID- 24452508
TI  - Conditioning of the abdominal cavity reduces tumor implantation in a laparoscopic
      mouse model.
AB  - PURPOSE: The addition of 4 % O2 and 10 % N2O to the CO2 pneumoperitoneum (PP),
      together with slight cooling and humidification (conditioning), contributes to
      reducing adhesions by preventing mesothelial damage. We investigated the effect
      of peritoneal damage during laparoscopy on tumor implantation. METHODS: In
      Experiment 1, different tumor cell concentrations were injected into control mice
      without PP and into mice with 60-min dry CO2PP (mesothelial damage). In
      Experiment 2, tumor cells were injected into control mice (group I) and in mice
      with mesothelial damage (group II). In groups III to VI, mesothelial damage was
      decreased by adding humidification, humidification + 10 % N2O, humidification +
      10 % N2O + 4 % O2, and conditioning, respectively. RESULTS: In Experiment 1, the
      tumors increased with the number of cells injected and with mesothelial damage in
      the abdominal cavity (p = 0.018) and abdominal wall (p < 0.0001). Experiment 2
      confirmed that 60 min of dry CO2PP increased the number of tumors in the
      abdominal cavity and wall (p = 0.026 and p = 0.003, respectively). The number of
      tumors was decreased in the abdominal cavity by conditioning (p = 0.030) and in
      the abdominal wall using humidified CO2 (p = 0.032) or conditioning (p = 0.026).
      CONCLUSIONS: Tumor implantation was enhanced by peritoneal damage (60 min of dry
      CO2PP and desiccation), but this was prevented by conditioning. If confirmed in
      humans, conditioning would become important for oncologic surgery.

PMID- 24452507
TI  - Factors affecting survival after resection of intrahepatic cholangiocarcinoma.
AB  - PURPOSE: This study aimed at assessing the prognostic factors of resection of
      intrahepatic cholangiocarcinoma (IHCC), which remain unclear. METHODS: Among 70
      patients with IHCC, who were admitted to our hospital between 1998 and 2011, 45
      (64 %) underwent resection and 25 had unresectable tumors. Univariate and
      multivariate analyses were conducted retrospectively to assess the factors
      influencing survival of the patients who underwent resection. RESULTS: The median
      survival times of the patients who underwent resection versus those who did not
      were 16 months versus 9 months, respectively (P < 0.001). Multivariate analysis
      identified residual tumor status (relative risk 4.12, P = 0.04) and pathological
      differentiation (relative risk 5.55, P = 0.04) as independent factors predicting
      survival. Patients who underwent R1 resection had a significantly higher rate of
      local recurrence than those who underwent R0 resection (P = 0.008). With R0
      resection, there were no significant differences in patterns and rates of
      recurrence between patients with narrow (<= 5 mm) versus wide (>5 mm) surgical
      margins. CONCLUSIONS: R0/1 resection and a well-differentiated tumor were found
      to be independent prognostic factors for long-term survival after IHCC resection.
      If R0 resection was achieved, the width of the negative surgical margin did not
      affect the patterns and rates of recurrence.

PMID- 24452509
TI  - Classification of diastolic function with phase-contrast cardiac magnetic
      resonance imaging: validation with echocardiography and age-related reference
      values.
AB  - OBJECTIVES: To investigate whether cardiac magnetic resonance phase-contrast
      imaging (PC-CMR) can determine left ventricular (LV) diastolic function in
      comparison to echocardiography (EC). BACKGROUND: Non-invasive evaluation of
      diastolic function is important for the diagnostic classification and risk
      stratification of patients with cardiomyopathies. With EC, diastolic function is
      classified based on the mitral blood flow, LV myocardial tissue Doppler
      velocities and pulmonary venous flow. PC-CMR has the potential to measure these
      parameters and may be an important tool to assess diastolic function in clinical
      routine. METHODS: In 36 patients with various cardiovascular diseases and 6
      healthy volunteers, we performed single-slice short-axis PC-CMR at the level of
      the mitral leaflet tip and the inflow of the pulmonary veins to generate EC
      comparable mitral E and A waves, septal and lateral e' and a' tissue velocities,
      and E/A and E/e' ratios. EC was performed after PC-CMR in all patients and six
      volunteers. Patients were classified into three groups of DD for both techniques.
      In addition, we evaluated 120 healthy volunteers as controls (3 age groups: 1 =
      20-35 years; 2 = 36-50 years; 3 >= 51 years) for reference values. RESULTS: PC
      CMR correlation with EC regarding the relation of mitral E and A velocities was
      good (r = 0.83, p < 0.001). The correlation for the mean septal and lateral E/e'
      ratio was high with r = 0.90 (p < 0.001). 40/42 subjects (95 %) were categorized
      correctly. The mean scan time for PC-CMR was 189 +/- 16 s and mean analysis time
      was 348 +/- 95 s. EC image acquisition time was slightly higher (201 +/- 37 s, p
      = n.s.), whereas EC image analysis time was significantly lower (149 +/- 23 s, p
      < 0.001). CONCLUSION: The classification of DD with PC-CMR is feasible and shows
      good agreement with the widely accepted EC classification of DD. We present a
      practical approach for the clinically important assessment of DD with PC-CMR,
      circumventing sophisticated and time-consuming CMR sequences and specially
      designed software analysis tools.

PMID- 24452510
TI  - Carboxylic acids in crystallization of macromolecules: learning from successful
      crystallization experiments.
AB  - The production of macromolecular crystals suitable for structural analysis is one
      of the most important and limiting steps in the structure determination process.
      Often, preliminary crystallization trials are performed using hundreds of
      empirically selected conditions. Carboxylic acids and/or their salts are one of
      the most popular components of these empirically derived crystallization
      conditions. Our findings indicate that almost 40 % of entries deposited to the
      Protein Data Bank (PDB) reporting crystallization conditions contain at least one
      carboxylic acid. In order to analyze the role of carboxylic acids in
      macromolecular crystallization, a large-scale analysis of the successful
      crystallization experiments reported to the PDB was performed. The PDB is
      currently the largest source of crystallization data, however it is not easily
      searchable. These complications are due to a combination of a free text format,
      which is used to capture information on the crystallization experiments, and the
      inconsistent naming of chemicals used in crystallization experiments. Despite
      these difficulties, our approach allows for the extraction of over 47,000
      crystallization conditions from the PDB. Initially, the selected conditions were
      investigated to determine which carboxylic acids or their salts are most often
      present in crystallization solutions. From this group, selected sets of
      crystallization conditions were analyzed in detail, assessing parameters such as
      concentration, pH, and precipitant used. Our findings will lead to the design of
      new crystallization screens focused around carboxylic acids. 

PMID- 24452511
TI  - Effect of a dedicated osteoporosis health professional on screening and treatment
      in outpatients presenting with acute low trauma non-hip fracture: a systematic
      review.
AB  - The aim of this study was to identify the effect a dedicated osteoporosis health
      professional on screening and treatment in outpatients presenting with acute low
      trauma fracture. A dedicated osteoporosis health professional improved
      investigation and management of osteoporosis. Osteoporosis management was
      enhanced, leading to the potential for future fracture prevention. PURPOSE: This
      study aimed to review the effect a dedicated osteoporosis health professional on
      screening and treatment in outpatients presenting with acute low trauma fracture.
      METHODS: We searched the electronic databases of Medline, EMBASE, CINAHL, Current
      Contents Connect, Joanna Briggs Institute EBP, and Cochrane from database
      development to April 2013, examined grey literature, and completed manual
      searches of reference lists to identify English language research that examined
      the effect that dedicated health professional input had on osteoporosis
      management with acute low trauma non-hip fracture in the outpatient setting.
      Outcomes were defined as the proportion of patients with investigation (bone
      mineral density (BMD) or blood screen); treated with vitamin D supplementation or
      antiresorptive agent; documented BMD reading change; recurrent fracture
      occurrence; or referral to specialist bone (osteoporosis) clinic. RESULTS: All
      studies with a suitable control group showed an increase in BMD screening in the
      intervention group (odds ratio (OR) 5.4, 95% confidence interval (CI) 4.3-6.9,
      P<0.0001). The effect on treatment initiation showed a significantly increased
      rate of antiresorptive+/-vitamin D therapy (OR 5.3, 95% CI 4.1-6.8, P<0.0001). No
      studies examined improvement or decline in BMD guiding clinical practice as an
      outcome. Two studies showed reduced fracture recurrence. The osteoporosis health
      professional significantly increased referrals to a specialist bone clinic (OR
      9.6, 95% CI 6.2-14.6, P<0.0001). CONCLUSIONS: The presence of a dedicated
      osteoporosis health professional coordinating a targeted intervention for
      outpatients with low trauma non-hip fracture improves investigation and
      management of osteoporosis, resulting in the potential for future fracture
      prevention.

PMID- 24452512
TI  - Effect of vitamin D in fracture healing in a child: case report.
AB  - In this report, we describe the effect of vitamin D and calcium supplementation
      on fracture healing in a young boy with a hypovitaminosis D who had a radius
      refracture. The radiographic evaluation of the callus formation shows a clear
      effect of vitamin D on fracture healing in absence of additional variables.
      INTRODUCTION: Fracture healing restores the tissue to its original physical and
      mechanical properties and it involves a complex multistep process that involves
      response to injury, intramembranous bone formation, chondrogenesis, endochondral
      bone formation, and bone remodeling. All this process is influenced by a variety
      of systemic and local factors. It is generally assumed that vitamin D plays an
      intimate role in healing fractures; however, very little data exists on how it
      does. CASE REPORT: In this report, the authors describe the effect of vitamin D
      and calcium supplementation on fracture healing in a young boy with a
      hypovitaminosis D who had a radius refracture. CONCLUSIONS: Our case report
      suggests that the hypovitaminosis D is a possible cause of inadequate fracture
      healing and refracture in children and it shows a clear effect of vitamin D
      supplementation on callus formation in the absence of additional variables.

PMID- 24452515
TI  - Kinetically controlled seed-mediated growth of narrow dispersed silver
      nanoparticles up to 120 nm: secondary nucleation, size focusing, and Ostwald
      ripening.
AB  - A facile synthesis method was developed based on the seed-mediated growth to get
      the narrow dispersed silver nanoparticles with controllable sizes ranging from 20
      nm to larger than 120 nm. Environmentally friendly glucose acts as a reducing
      agent. Because of its weak reducing ability, the secondary nucleation is
      prevented in the seed-mediated growth, and the size of silver nanoparticles can
      be tuned continuously by the continuous addition of reactants. Controlling the
      supersaturation level is critical to suppress both the nucleation and Ostwald
      ripening, which can be realized by carefully controlling the addition rate of the
      reactants. We also set up a convenient method to determine the size and size
      distribution of silver nanoparticles from the size-dependent absorption spectra
      of the colloids, and optimize the growth parameters using this method to get
      narrow dispersed silver nanoparticles. 

PMID- 24452514
TI  - Comprehensive microRNA profiling of prostate cancer cells after ionizing
      radiation treatment.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene
      expression and have emerged as potential biomarkers in radiation response to
      human cancer. Only a few miRNAs have been identified in radiation response to
      prostate cancer and the involvement of the radiation-associated miRNA machinery
      in the response of prostate cancer cells to radiation is not thoroughly
      understood. Therefore, the purpose of the present study was to comprehensively
      investigate the expression levels, arm selection preference and isomiRs of
      radiation-response miRNAs in radiation-treated PC3 cells using a next-generation
      sequencing (NGS) approach. Our data revealed that the arm selection preference
      and 3' modification of miRNAs may be altered in prostate cancer after radiation
      exposure. In addition, the proportion of AA dinucleotide modifications at the end
      of the read gradually increased in a time-dependent manner after PC3 radiation
      treatment. We also identified 6 miRNAs whose expression increased and 16 miRNAs
      whose expression decreased after exposure to 10 Gy of radiation. A pathway
      enrichment analysis revealed that the target genes of these radiation-induced
      miRNAs significantly co-modulated the radiation response pathway, including the
      mitogen-activated protein kinase (MAPK), Wnt, transforming growth factor-beta
      (TGF-beta) and ErbB signaling pathways. Furthermore, analysis of The Cancer
      Genome Atlas (TCGA) database revealed that the expression of these radiation
      induced miRNAs was frequently dysregulated in prostate cancer. Our study
      identified radiation-induced miRNA candidates which may contribute to
      radiosensitivity and can be used as biomarkers for radiotherapy.

PMID- 24452517
TI  - Quantitative determination of ketoconazole by UPLC-MS/MS in human plasma and its
      application to pharmacokinetic study.
AB  - In this study, a simple, rapid and sensitive ultra-performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) method is described for
      determination of ketoconazole (KTZ) in human plasma samples using carbamazepine
      as the internal standard (IS). Sample preparation was accomplished through one
      step liquid-liquid extraction by ethyl acetate, and chromatographic separation
      was performed on an Acquity BEH C18 column (2.1 mm*50 mm, 1.7 MUm) with gradient
      profile at a flow of 0.45 mL/min. Mass spectrometric analysis was performed using
      a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI)
      source in the positive ion mode. The MRM transition of m/z 531.2->489.3 was used
      to quantify for KTZ. The linearity of this method was found to be within the
      concentration range of 5-15 000 ng/mL for KTZ in human plasma. Only 1.5 min was
      needed for an analytical run. The method herein described was superior to
      previous methods and was successfully applied to the pharmacokinetic study of KTZ
      in healthy Chinese volunteers after oral administration. 

PMID- 24452518
TI  - A proteomic analysis using an animal model for hyperlipidemia-related erectile
      dysfunction.
AB  - To investigate the pathogenesis of hyperlipidemia-related erectile dysfunction
      and the effects of DA-8159, a new phosphodiesterase-5 inhibitor, on protein
      expression, we performed a proteomic analysis of differentially expressed
      proteins in the corpus cavernosum of hyperlipidemic rats by two-dimensional
      electrophoresis-mass spectrometry. Rats were fed high-cholesterol diet and
      treated with 5 mg.kg(-1).day(-1) DA-8159 concurrently. After 5 months apparent
      hyperlipidemia and significantly decreased maximal intra-cavernous pressure were
      observed in the control group with the alteration of 8 proteins, which were
      restored by DA-8159 treatment. The proteins whose levels decreased >2-fold and
      attenuated by DA-8159 were determined alcohol dehydrogenase, aldolase A, annexin
      1, and tropomyosin-rat, whereas proteins increased>2-fold and recovered by DA
      8159 were found to be aldehyde dehydrogenase complex, guanine deaminase, creatine
      kinase-B, and phosphoglycerate mutase type B subunit.

PMID- 24452519
TI  - Saliva vs. plasma bioequivalence of paracetamol in humans: validation of class I
      drugs of the salivary excretion classification system.
AB  - AIMS: To study saliva and plasma bioequivalence of paracetamol in healthy human
      volunteers, and to investigate the robustness of using saliva instead of plasma
      as surrogate for bioequivalence of class I drugs according to the salivary
      excretion classification system (SECS). METHODS: Saliva and plasma
      pharmacokinetic parameters were calculated by non compartmental analysis.
      Analysis of variance, 90% confidence intervals, intra-subject and inter-subject
      variability values of pharmacokinetic parameters were calculated after
      logarithmic transformation. Calculations were done using Kinetica program V5.
      Descriptive and comparative statistics were also calculated by Excel. RESULTS AND
      DISCUSSION: Paracetamol falls into class I (High permeability/High fraction
      unbound to plasma proteins) and was subjected to salivary excretion, with
      correlation coefficient of 0.99 between saliva and plasma concentrations and
      saliva/plasma concentrations ratios of 1.45-1.50. The 90% confidence limits of
      areas under curve (AUC(last) and AUC(infinity)) showed similar trend and passed
      the 80-125% acceptance criteria in both saliva and plasma. On the other hand for
      maximum concentration (C(max)), the 90% confidence limits passed the acceptance
      criteria in plasma and failed in saliva. Inter and intra subject variability
      values in saliva were higher than plasma leading to need for higher number of
      subjects to be used in saliva. Saliva and plasma parameter ratios were not
      significantly different (P>0.05). CONCLUSIONS: Saliva instead of plasma can be
      used as surrogate for bioequivalence of class I drugs according to SECS when
      adequate sample size is used. Future work is planned to demonstrate SECS
      robustness in drugs that fall into classes II or III.

PMID- 24452520
TI  - Saliva vs. plasma bioequivalence of metformin in humans: validation of class II
      drugs of the salivary excretion classification system.
AB  - To study saliva and plasma bioequivalence of metformin in humans, and to
      investigate the robustness of using saliva instead of plasma as surrogate for
      bioequivalence of class II drugs according to the salivary excretion
      classification system (SECS).Plasma and saliva samples were collected for 12 h
      after 500 mg oral dosing of metformin to 16 healthy humans. Plasma and saliva
      pharmacokinetic parameters, 90% confidence intervals and intra-subject
      variability values were calculated using Kinetica V5. Descriptive statistics and
      dimensional analysis were calculated by Excel. SimCYP program V13 was used for
      estimation of effective intestinal permeability.Metformin was subjected to
      salivary excretion since it falls into class II (Low permeability/High fraction
      unbound to plasma proteins), with correlation coefficients of 0.95-0.99 between
      plasma and saliva concentrations. Saliva/plasma concentration ratios were 0.29
      0.39. The 90% confidence limits of all parameters failed in both saliva and
      plasma. Intra-subject variability values in saliva were higher than plasma
      leading to need for higher number of subjects to be used in saliva.Saliva instead
      of plasma can be used as surrogate for bioequivalence of class II drugs according
      to SECS when adequate sample size is used. Future work is planned to demonstrate
      SECS robustness in drugs that fall into class III. 

PMID- 24452521
TI  - UPLC-MS/MS determination of phentolamine in human plasma and its application to a
      pharmacokinetic study.
AB  - A sensitive and rapid ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS) method was developed to determine phentolamine in human
      plasma. Sample preparation was accomplished through a simple liquid-liquid
      extraction with ethyl acetate. Chromatographic separation was carried out on an
      Acquity UPLC BEH C18 column using an isocratic mobile phase system composed of
      acetonitrile and 1% formic acid in water (33:67, v/v) at a flow rate of 0.45
      mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass
      spectrometer coupled with an electro-spray ionization (ESI) source in the
      positive ion mode. The MRM transitions of m/z 282.1 -> 212.0 and m/z 237.1 ->
      194.2 were used to quantify for phentolamine and carbamazepine (internal
      standard, IS), respectively. The linearity of this method was found to be within
      the concentration range of 0.5-100.0 ng/mL with a lower limit of quantification
      of 0.5 ng/mL. Only 1.0 min was needed for an analytical run. This fully validated
      method was successfully applied to the pharmacokinetic study after oral
      administration of 60 mg phentolamine to 20 Chinese healthy male volunteers. 

PMID- 24452522
TI  - An intra-hippocampal injection of nandrolone induces learning and memory
      impairments in rat.
AB  - This study was investigated to evaluate the effect of intra-hippocampal injection
      of the nandrolone on spatial learning task in rats. The drug or vehicle was
      manually injected into the hippocampus with a 10-ul Hamilton syringe attached via
      polyethylene tubing to 27-gauge stainless-steel injection cannula. After 6 days
      of recovery, learning behaviors were evaluated using an 8-arm radial maze. The
      results showed that intra-hippocampal injection of nandrolone can impair trained
      spatial learning at a dose of 5 ul. We also observed a dense cytoplasm and
      nucleus in CA1 neurons as well as signs of necrosis. Nandrolone can impair the
      time required to reach the baited arm as well as the frequency of successful arm
      entries. At the 10 ul dose of nandrolone, neural hypertrophy and increased
      dentate gyrus volume were also observed. 

PMID- 24452523
TI  - Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)
      5-aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide derivatives.
AB  - 28 new 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-1H-pyrazole-1
      carbothioamide derivatives were synthesized and evaluated in vitro for their
      monoamine oxidase (MAO) A and B inhibitory activity and selectivity. The
      derivatives substituted by halogen on the fifth position of pyrazole ring,
      inhibited MAO-A enzyme with a high selectivity index. On the other hand,
      compounds substituted with 2-naphthyl inhibited MAO-B enzyme with a moderate
      selectivity index. Docking studies were done to highlight the interactions of the
      most active derivative with the active site of MAO-A. In addition, in vivo
      antidepressant and anxiolytic activities of the compounds having selective MAO-A
      inhibitory effects, were investigated by using Porsolt forced swimming and
      elevated plus-maze tests respectively. 3-(4-Fluorophenyl)-5-(4-chloro-phenyl)-N
      allyl-4,5-dihydro-1H-pyrazole-1-carbothio-amide has antidepressant, 3-(4
      fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1
      carbothioamide and 3-(4-fluoro-phenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H
      pyrazole-1-carbothioamide have anxiolytic activity. 

PMID- 24452525
TI  - Ruthenium-catalyzed ortho-arylation of acetanilides with aromatic boronic acids:
      an easy route to prepare phenanthridines and carbazoles.
AB  - The highly regioselective ortho-arylation of acetanilides with aromatic boronic
      acids in the presence of a Ru(II) complex (3 mol%), AgSbF6 (12 mol%), Cu(OTf)2
      (20 mol%) and Ag2O (1.0 eq.) is described. Later, ortho-arylated acetanilides
      were converted into phenanthridine and carbazole derivatives by using Ph3PO and
      Tf2O or palladium or Cu(OTf)2 catalysts.

PMID- 24452524
TI  - Non-clinical pharmacokinetic/pharmacodynamic and early clinical studies
      supporting development of a novel subcutaneous formulation for the monoclonal
      antibody rituximab.
AB  - This overview article describes the non-clinical pharmacology, pharmacokinetic
      and clinical dose-finding programs supporting the development of a novel
      subcutaneous formulation for rituximab, a monoclonal antibody that selectively
      targets CD20-positive B-lymphocytes. The subcutaneous route of administration is
      expected to improve convenience for patients and to reduce healthcare
      professional resource use compared with conventional intravenous infusion.
      Various non-clinical and clinical studies were conducted to support the bridge
      from the approved intravenous formulation to the novel subcutaneous treatment.
      The underlying hypothesis for these studies was that achieving subcutaneous
      rituximab serum trough concentrations that are at least as high as those reached
      with the intravenous formulation would result in at least the same degree of
      receptor saturation. Preclinical mouse xenograft and cynomolgus monkey B-cell
      depletion studies were performed at intravenous and subcutaneous doses that were
      previously found to result in comparable serum concentrations in pharmacokinetic
      studies in the same species. Results from these non-clinical assessments guided
      dose selection for the subsequent phase 1b dose finding trials in patients with
      follicular lymphoma as part of maintenance treatment. A fixed dose of 1 400 mg
      was found to result in noninferior serum trough concentrations to the intravenous
      formulation. Clinical trials in the induction setting in patients with follicular
      lymphoma and chronic lymphocytic leukemia are currently ongoing. 

PMID- 24452526
TI  - Pulmonary toxocariasis: a case report and literature review.
AB  - Toxocariasis is a parasitic disease caused by Toxocara canis or T. cati. We
      report a patient with toxocariasis who presented with dyspnea, high-grade
      eosinophilia, and bilateral pulmonary nodules. To further characterize the
      pulmonary manifestations of toxocariasis, we have reviewed 11 previously
      published pulmonary toxocariasis cases. The most common pulmonary symptoms in our
      review were cough and dyspnea, and the most common finding on chest imaging was
      bilateral pulmonary nodules. Risk factors for Toxocara infection primarily
      included exposure to dogs. Most patients received albendazole and responded well.
      A high index of suspicion is needed to diagnose this otherwise preventable
      parasitic disease.

PMID- 24452527
TI  - Homo- and heteropolymetallic 3-(2-pyridyl)pyrazolate manganese and rhenium
      complexes.
AB  - fac-[MBr(CO)3(pypzH)] (M = Mn, Re; pypzH = (3-(2-pyridyl)pyrazole) complexes are
      prepared from fac-[MBr(CO)3(NCMe)2] and pypzH. The result of their deprotonation
      depends on the metallic substrate: the rhenium complex affords cleanly the
      bimetallic compound [fac-{Re(CO)3(MU(2)-pypz)}]2 (MU(2)-pypz = MU(2)-3-(2-pyridyl
      kappa(1)N)pyrazolate-2kappa(1)N), which was crystallographically characterized,
      whereas a similar manganese complex was not detected. When two equivalents of
      pyridylpyrazolate are used, polymetallic species [fac-M(CO)3(MU(2)-pypz)(MU(3)
      pypz)M'] (MU(3)-pypz = MU(3)-3-(2-pyridyl-kappa(1)N)pyrazolate
      1kappa(2)N,N:2kappa(1)N:; M = Mn, M' = Li, Na, K; M = Re, M' = Na) are obtained.
      The crystal structures of the manganese carbonylate complexes were determined.
      The lithium complex is a monomer containing one manganese and one lithium atom,
      whereas the sodium and potassium complexes are dimers and reveal an unprecedented
      coordination mode for the bridging 3-(2-pyridyl)pyrazolate ligand, where the
      nitrogen of the pyridyl fragment and the nitrogen-1 of pyrazolate are chelated to
      manganese atoms, and each nitrogen-2 of pyrazolate is coordinated to two alkaline
      atoms. The polymetallic carbonylate complexes are unstable in solution and evolve
      spontaneously to [fac-{Re(CO)3(MU(2)-pypz)}]2 or to the trimetallic paramagnetic
      species [Mn(II)(MU(2)-pypz)2{fac-{Mn(I)(CO)3(MU(2)-pypz)}2}]. The related complex
      cis-[MnCl2(pypzH)2] was also synthesized and structurally characterized. The
      electrochemical behavior of the new homo- and heteropolymetallic 3-(2
      pyridyl)pyrazolate complexes has been studied and details of their redox
      properties are reported. 

PMID- 24452528
TI  - "A community with diversity of culture, wealth, resources, and living
      experiences": defining neighborhood in an unincorporated community.
AB  - To obtain a better understanding of how people living in an unincorporated region
      define their neighborhood, a long-term photovoice project was conducted. Thirty
      one photovoice sessions and eight structured interviews were coded and analyzed
      to assess participants' neighborhood definitions. Participant's difficulties in
      identifying the geographic, physical and demographic characteristics of their
      neighborhood led them to use social interactions, place-mediated values, and
      civic engagement to define neighborhood. 

PMID- 24452529
TI  - Barriers to addressing substance abuse in domestic violence court.
AB  - Substance abuse commonly co-occurs with intimate partner violence among both
      perpetrators and survivors. Specialized courts that focus on intimate partner
      violence provide a unique opportunity to address both problems simultaneously,
      but research has yet to identify whether this happens. In this qualitative study
      of a domestic violence court in a large midwestern metropolitan area, key
      informants were interviewed to understand how the Court treats substance abuse.
      Results indicate that substance abuse typically is not identified among
      perpetrators or survivors going through the Court unless it is mentioned in a
      police report. Barriers to such identification are the organization of the Court,
      bounded definition of actors' roles in the Court, limited resources, and negative
      attitudes towards survivors. These results suggest that specialized courts that
      attend to only one problem may overlook the possibility of addressing issues that
      commonly co-occur. 

PMID- 24452530
TI  - Generation and characterization of immortalized rat retinal microglial cell
      lines.
AB  - Retinal microglia play an important role as resident immunocompetent and
      phagocytic cells in the event of injury and disease. Retinal microglia and
      microglia precursor transplantation show a rescue effect in ischemic retina and
      retinal degeneration. However, studies of retinal microglia have been hampered by
      the difficulty of obtaining sufficient numbers of microglia. One way to
      circumvent this difficulty is to establish permanent retinal microglia cell
      lines. In the present study, we report the generation of immortalized retinal
      microglia, T-MG cells, from postnatal day 3 rat retinal tissue using a lentiviral
      vector encoding SV40 large T antigen. The T-MG cells exhibited cell-type-specific
      antigens for monocyte/macrophage lineage cells, including CD11b (OX42), ED1
      (OX6), and Iba1, and actively phagocytosed latex beads. In addition to primary
      retinal microglia, T-MG cells also have the ability to recruit into chemokines.
      Treatment of T-MG cells with lipopolysaccharide (LPS) led to increased levels of
      tumor necrosis factor-alpha, interleukin-1beta, and inducible nitric oxide
      synthase. Genome-wide microarray analysis showed a less than 1% difference in the
      genes between the T-MG cells and the control primary retinal microglia. The T-MG
      cells exhibited properties similar to those of the primary retinal microglia and
      should have considerable utility as an in vitro model for the study of retinal
      microglia in health and as a curative therapy and an in vivo model for the study
      of retinal microglia in disease.

PMID- 24452531
TI  - The animal in you: animalistic descriptions of a violent crime increase
      punishment of perpetrator.
AB  - Criminal acts are sometimes described using animal metaphors. What is the impact
      of a violent crime being described in an animalistic versus a non-animalistic way
      on the subsequent retribution toward the perpetrator? In two studies, we
      experimentally varied animalistic descriptions of a violent crime and examined
      its effect on the severity of the punishment for the act. In Study 1, we showed
      that compared to non-animalistic descriptions, animalistic descriptions resulted
      in significantly harsher punishment for the perpetrator. In Study 2, we
      replicated this effect and further demonstrated that this harsher sentencing is
      explained by an increase in perceived risk of recidivism. Our findings suggest
      that animalistic descriptions of crimes lead to more retaliation against the
      perpetrator by inducing the perception that he is likely to continue engaging in
      violence.

PMID- 24452532
TI  - Photonic simulation of topological excitations in metamaterials.
AB  - Condensed matter systems with topological order and metamaterials with left
      handed chirality have attracted recently extensive interests in the fields of
      physics and optics. So far the topological order and chirality of electromagnetic
      wave are two independent concepts, and there is no work to address their
      connection. Here we propose to establish the relation between the topological
      order in condensed matter systems and the chirality in metamaterials, by mapping
      explicitly Maxwell's equations to the Dirac equation in one dimension. We report
      an experimental implement of the band inversion in the Dirac equation, which
      accompanies change of chirality of electromagnetic wave in metamaterials, and the
      first microwave measurement of topological excitations and topological phases in
      one dimension. Our finding provides a proof-of-principle example that
      electromagnetic wave in the metamaterials can be used to simulate the topological
      order in condensed matter systems and quantum phenomena in relativistic quantum
      mechanics in a controlled laboratory environment. 

PMID- 24452533
TI  - Molecular profiling of chordoma.
AB  - The molecular basis of chordoma is still poorly understood, particularly with
      respect to differentially expressed genes involved in the primary origin of
      chordoma. In this study, therefore, we compared the transcriptional expression
      profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U
      CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high
      density oligonucleotide array. The expression of 65 genes whose mRNA levels
      differed significantly (p<0.001; >=6-fold change) between chordoma and control
      (vertebral disc) was identified. Genes with increased expression in chordoma
      compared to control and chondrosarcoma were most frequently located on
      chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics
      of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q
      (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were
      confirmed for selected genes by quantitative polymerase chain reaction analysis.
      As in other studies, we showed the expression of brachyury. We demonstrate the
      expression of new potential candidates for chordoma tumorigenesis, such as CD24,
      ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and
      others. Thus, we identified and validated a set of interesting candidate genes
      whose differential expression likely plays a role in chordoma.

PMID- 24452534
TI  - Extract of Aronia melanocarpa-modified hemostasis: in vitro studies.
AB  - PURPOSE: Aronia melanocarpa has an extremely high content of procyanidins and
      anthocyanins. The multidirectional benefits of consumption of these berries are
      widely reported. Although numerous studies confirmed the influence of polyphenols
      on various stages of hemostasis, the exact mechanism of this phenomenon is not
      understood. The aim of our study was to evaluate the in vitro effect of A.
      melanocarpa extract on various parameters of hemostasis. METHODS: Adenosine 5'
      diphosphate (ADP)-induced aggregation was measured with turbidimetric method.
      Spontaneous and ADP-activated platelet adhesion were investigated using a
      colorimetric method. The global assay of coagulation and fibrinolysis was
      performed with the use of optical clotting and lysis (CL) test. Thrombin (0.5
      IU/mL) and tissue plasminogen activator (60 ng/mL) were used to obtain a CL
      curve. The activity of thrombin and plasmin was determined by means of
      chromogenic substrate (S-2238, S-2251) RESULTS: The aronia extract contributed to
      the reduction in spontaneous and ADP-activated platelet adhesion. A significant
      increase in overall potential of CL as well as significant changes in key
      parameters of these processes (T t-thrombin time, F vo-initial plasma clotting
      velocity, and L max-maximum lysis) was reported. Chokeberry extract significantly
      inhibited the amidolytic activity of thrombin and plasmin. CONCLUSION: Our in
      vitro findings indicate a complex mechanism of influence of chokeberry
      polyphenols on platelet activity and the overall potential of CL. We confirmed
      that chokeberry inhibits the amidolytic activity of thrombin. It was demonstrated
      for the first time that chokeberry polyphenols inhibit the amidolytic activity of
      another serine protease, i.e., plasmin, which is the main fibrinolytic enzyme.
      Furthermore, our research points out a significant contribution of other plasma
      components and fibrinogen in the modulation of hemostasis by polyphenols.

PMID- 24452535
TI  - A comprehensive assessment of parental age and psychiatric disorders.
AB  - IMPORTANCE: There has been recent interest in the findings that the offspring of
      older fathers have an increased risk of both de novo mutations and
      neuropsychiatric disorders. However, the offspring of younger parents are also at
      risk for some adverse mental health outcomes. OBJECTIVE: To determine the
      association between maternal and paternal age and a comprehensive range of mental
      health disorders. DESIGN, SETTING, AND PARTICIPANTS: A comprehensive, population
      based record linkage study using the Danish Psychiatric Central Research Register
      from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons
      born in Denmark from January 1, 1955, through December 31, 2006, were followed up
      during the study period. EXPOSURES: Maternal and paternal age at the time of
      offspring's birth. MAIN OUTCOMES AND MEASURES: We examined a broad range of
      International Classification of Diseases-defined mental disorders, including
      substance use; schizophrenia and related disorders; mood disorders; neurotic,
      stress-related, and somatoform disorders; eating disorders; specific personality
      disorders; and a range of developmental and childhood disorders. The incidence
      rate ratios for each mental disorder outcome were estimated by log linear Poisson
      regression with adjustments for the calendar period, age, sex, and age of the
      other parent. RESULTS: The cohort was observed for 42.7 million person-years,
      during which 218 441 members of the cohort had their first psychiatric contact
      for any psychiatric disorder. Based on the overall risk of psychiatric disorders,
      the offspring of younger and older parents were at increased risk compared with
      those of parents aged 25 to 29 years. When the offspring were examined for
      particular disorders, the nature of the relationship changed. For example, the
      offspring of older fathers were at an increased risk of schizophrenia and related
      disorders, mental retardation, and autism spectrum disorders. In contrast, the
      offspring of young mothers (and to a lesser extent young fathers) were at an
      increased risk for substance use disorders, hyperkinetic disorders, and mental
      retardation. CONCLUSIONS AND RELEVANCE: The offspring of younger mothers and
      older fathers are at risk for different mental health disorders. These
      differences can provide clues to the complex risk architecture underpinning the
      association between parental age and the mental health of offspring.

PMID- 24452536
TI  - Differential selection in HIV-1 gp120 between subtype B and East Asian variant
      B'.
AB  - HIV-1 evolves strongly and undergoes geographic differentiation as it spreads in
      diverse host populations around the world. For instance, distinct genomic
      backgrounds can be observed between the pandemic subtype B, prevalent in Europe
      and North-America, and its offspring clade B' in East Asia. Here we ask whether
      this differentiation affects the selection pressure experienced by the virus. To
      answer this question we evaluate selection pressure on the HIV-1 envelope protein
      gp120 at the level of individual codons using a simple and fast estimation method
      based on the ratio k a /k s of amino acid changes to synonymous changes. To
      validate the approach we compare results to those from a state-of-the-art mixed
      effect method. The agreement is acceptable, but the analysis also demonstrates
      some limitations of the simpler approach. Further, we find similar distributions
      of codons under stabilizing and directional selection pressure in gp120 for
      subtypes B and B' with more directional selection pressure in variable loops and
      more stabilizing selection in the constant regions. Focusing on codons with
      increased k a /k s values in B', we show that these codons are scattered over the
      whole of gp120, with remarkable clusters of higher density in regions flanking
      the variable loops. We identify a significant statistical association of
      glycosylation sites and codons with increased k a /k s values. 

PMID- 24452537
TI  - The phenotype and activation status of regulatory T cells during Friend
      retrovirus infection.
AB  - The suppressive capacity of regulatory T cells (Tregs) has been extensively
      studied and is well established for many diseases. The expansion, accumulation,
      and activation of Tregs in viral infections are of major interest in order to
      find ways to alter Treg functions for therapeutic benefit. Tregs are able to
      dampen effector T cell responses to viral infections and thereby contribute to
      the establishment of a chronic infection. In the Friend retrovirus (FV) mouse
      model, Tregs are known to expand in all infected organs. To better understand the
      characteristics of these Treg populations, their phenotype was analyzed in
      detail. During acute FV-infection, Tregs became activated in the spleen and bone
      marrow, as indicated by various T cell activation markers, such as CD43 and
      CD103. Interestingly, Tregs in the bone marrow, which contains the highest viral
      loads during acute infection, displayed greater levels of activation than Tregs
      from the spleen. Treg expansion was driven by proliferation but no FV-specific
      Tregs could be detected. Activated Tregs in FV-infection did not produce Granzyme
      B (GzmB) or tumor necrosis factor alpha (TNFalpha), which are thought to be a
      potential mechanism for their suppressive activity. Furthermore, Tregs expressed
      inhibitory markers, such as TIM3, PD-1 and PD-L1. Blocking TIM3 and PD-L1 with
      antibodies during chronic FV-infection increased the numbers of activated Tregs.
      These data may have important implications for the understanding of Treg
      functions during chronic viral infections. 

PMID- 24452538
TI  - Construction of a chimeric hepatitis C virus replicon based on a strain isolated
      from a chronic hepatitis C patient.
AB  - Subgenomic replicons of hepatitis C virus (HCV) have been widely used for
      studying HCV replication. Here, we report a new subgenomic replicon based on a
      strain isolated from a chronically infected patient. The coding sequence of HCV
      was recovered from a Chinese chronic hepatitis C patient displaying high serum
      HCV copy numbers. A consensus sequence designated as CCH strain was constructed
      based on the sequences of five clones and this was classified by sequence
      alignment as belonging to genotype 2a. The subgenomic replicon of CCH was
      replication-deficient in cell culture, due to dysfunctions in NS3 and NS5B.
      Various JFH1/CCH chimeric replicons were constructed, and specific mutations were
      introduced. The introduction of mutations could partially restore the replication
      of chimeric replicons. A replication-competent chimeric construct was finally
      obtained by the introduction of NS3 from JFH1 into the backbone of the CCH
      strain. 

PMID- 24452539
TI  - New therapeutic vaccination strategies for the treatment of chronic hepatitis B.
AB  - Chronic hepatitis B virus (CHB) is currently treated with either interferon-based
      or nucleot(s)ide-based antiviral therapies. However, treatment with pegylated
      interferon alpha results in a durable antiviral response in only about 30%
      patients and is associated with side effects. Most patients receiving
      nucleot(s)ide analogue treatment do not establish long-term, durable control of
      infection and have rebounding viremia after cessation of therapy. Thus, novel
      therapy strategies are necessary to achieve the induction of potent and durable
      antiviral immune responses of the patients which can maintain long-term control
      of viral replication. Therapeutic vaccination of HBV carriers is a promising
      strategy for the control of hepatitis B. Here the authors review new therapeutic
      vaccination strategies to treat chronic hepatitis B which may be introduced for
      patient treatment in the future. 

PMID- 24452541
TI  - Role of hepatitis C virus in B cell lymphoproliferations.

PMID- 24452540
TI  - Interplay between hepatitis B virus and the innate immune responses: implications
      for new therapeutic strategies.
AB  - Hepatitis B virus (HBV) infection is still a worldwide health problem; however,
      the current antiviral therapies for chronic hepatitis B are limited in efficacy.
      The outcome of HBV infection is thought to be the result of complex interactions
      between the HBV and the host immune system. While the role of the adaptive immune
      responses in the resolution of HBV infection has been well characterized, the
      contribution of innate immune mechanisms remains elusive until recent evidence
      implicates that HBV appears to activate the innate immune response and this
      response is important for controlling HBV infection. Here, we review our current
      understanding of innate immune responses to HBV infection and the multifaceted
      evasion by the virus and discuss the potential strategies to combat chronic HBV
      infection via induction and restoration of host innate antiviral responses. 

PMID- 24452542
TI  - The two faces of vaccine-induced immune response: protection or increased risk of
      HIV infection?!

PMID- 24452543
TI  - Ficolins and infectious diseases.
AB  - Ficolins are serum complement lectins, with a structure similar to mannose
      binding lectin (MBL) and lung surfactant protein (SP)-A and SP-D. Ficolins
      activate the lectin complement system and play important roles in host innate
      immunity. Ficolins are members of the collectin family of proteins, which act as
      pattern recognition receptors (PRRs). They are soluble oligomeric defense
      proteins with lectin-like activity, and are able to recognize pathogen-associated
      molecular patterns (PAMPs), which are carbohydrate molecules on the surface of
      pathogens, and of apoptotic, necrotic, and malignant cells. Upon binding to their
      specific PAMPs, ficolins may trigger activation of the immune system either (1)
      by initiating activation of complement via the lectin pathway, (2) by a primitive
      type of opsonophagocytosis, or (3) by stimulating secretion of the inflammatory
      cytokines interferon (IFN)-Gamma, interleukin (IL)-17, IL-6, and tumor necrosis
      factor (TNF)-alpha, and production of nitric oxide (NO) by macrophages, thus
      limiting the infection and concurrently orchestrating the subsequent adaptive
      immune response. Recently, a number of reports have shown that dysfunction or
      abnormal expression of ficolins may play crucial roles in viral and bacterial
      diseases and in inflammation. This review summarizes the reports on the roles of
      ficolins in the infectious diseases, and provides insight into ficolins as novel
      innate immune therapeutic options to treat these diseases. 

PMID- 24452544
TI  - Central sympathetic innervations to visceral and subcutaneous white adipose
      tissue.
AB  - There is a link between visceral white adipose tissue (WAT) and the metabolic
      syndrome in humans, with health improvements produced with small visceral WAT
      reduction. By contrast, subcutaneous WAT provides a site for lipid storage that
      is rather innocuous relative to ectopic lipid storage in muscle or liver. The
      sympathetic nervous system (SNS) is the principal initiator for lipolysis in WAT
      by mammals. Nothing is known, however, about the central origins of the SNS
      circuitry innervating the only true visceral WAT in rodents, mesenteric WAT
      (MWAT), which drains into the hepatic portal vein. We tested whether the central
      sympathetic circuits to subcutaneous [inguinal WAT (IWAT)] and visceral WAT
      (MWAT) are separate or shared and whether they possess differential sympathetic
      drives with food deprivation in Siberian hamsters. Using two isogenic strains of
      pseudorabies virus, a retrograde transneuronal viral tract tracer within the same
      hamsters, we found some overlap (~20-55% doubly infected neurons) between the two
      circuitries across the neural axis with lesser overlap proximal to the depots
      (spinal cord and sympathetic chain) and with more neurons involved in the
      innervation of IWAT than MWAT in some brain regions. Food deprivation triggered a
      greater sympathetic drive to subcutaneous (IWAT) than visceral (MWAT) depots.
      Collectively, we demonstrated both shared and separate populations of brain,
      spinal cord, and sympathetic chain neurons ultimately project to a subcutaneous
      WAT depot (IWAT) and the only visceral WAT depot in rodents (MWAT). In addition,
      the lipolytic stimulus of food deprivation only increased SNS drive to
      subcutaneous fat (IWAT).

PMID- 24452546
TI  - High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with
      adenine-induced chronic renal failure.
AB  - This study examined the effects of 2 wk of high-NaCl diet on kidney function and
      dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced
      chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow
      containing adenine or were pair-fed an identical diet without adenine (controls).
      After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl)
      or to be switched to high 4% NaCl chow. Two weeks after randomization, renal
      clearance experiments were performed under isoflurane anesthesia and dynamic
      RBFA, baroreflex sensitivity (BRS), systolic arterial pressure variability
      (SAPV), and heart rate variability were assessed by spectral analytical
      techniques. Rats with ACRF showed marked reductions in glomerular filtration rate
      and renal blood flow (RBF), whereas mean arterial pressure and SAPV were
      significantly elevated. In addition, spontaneous BRS was reduced by ~50% in ACRF
      animals. High-NaCl diet significantly increased transfer function fractional gain
      values between arterial pressure and RBF in the frequency range of the myogenic
      response (0.06-0.09 Hz) only in ACRF animals (0.3 +/- 4.0 vs. -4.4 +/- 3.8 dB; P
      < 0.05). Similarly, a high-NaCl diet significantly increased SAPV in the low
      frequency range only in ACRF animals. To conclude, a 2-wk period of a high-NaCl
      diet in ACRF rats significantly impaired dynamic RBFA in the frequency range of
      the myogenic response and increased SAPV in the low-frequency range. These
      abnormalities may increase the susceptibility to hypertensive end-organ injury
      and progressive renal failure by facilitating pressure transmission to the
      microvasculature.

PMID- 24452545
TI  - Brown adipose tissue thermogenesis contributes to emotional hyperthermia in a
      resident rat suddenly confronted with an intruder rat.
AB  - Body temperature increases when individuals experience salient, emotionally
      significant events. There is controversy concerning the contribution of
      nonshivering thermogenesis in brown adipose tissue (BAT) to emotional
      hyperthermia. In the present study we compared BAT, core body, and brain
      temperature, and tail blood flow, simultaneously measured, to determine whether
      BAT thermogenesis contributes to emotional hyperthermia in a resident Sprague
      Dawley rat when an intruder rat, either freely-moving or confined to a small
      cage, is suddenly introduced into the cage of the resident rat for 30 min.
      Introduction of the intruder rat promptly increased BAT, body, and brain
      temperatures in the resident rat. For the caged intruder these temperature
      increases were 1.4 +/- 0.2, 0.8 +/- 0.1, 1.0 +/- 0.1 degrees C, respectively,
      with the increase in BAT temperature being significantly greater (P < 0.01) than
      the increases in body and brain. The initial 5-min slope of the BAT temperature
      record (0.18 +/- 0.02 degrees C/min) was significantly greater (P < 0.01) than
      the corresponding value for body (0.10 +/- 0.01 degrees C/min) and brain (0.09 +/
      0.02 degrees C/min). Tail artery pulse amplitude fell acutely when the intruder
      rat was introduced, possibly contributing to the increases in body and brain
      temperature. Prior blockade of beta3 adrenoceptors (SR59230A 10 mg/kg ip)
      significantly reduced the amplitude of each temperature increase. Intruder-evoked
      increases in BAT temperature were similar in resident rats maintained at 11
      degrees C for 3 days. In the caged intruder situation there is no bodily contact
      between the rats, so the stimulus is psychological rather than physical. Our
      study thus demonstrates that BAT thermogenesis contributes to increases in body
      and brain temperature occurring during emotional hyperthermia.

PMID- 24452547
TI  - Nutrient-specific feeding and endocrine effects of jejunal infusions in obese
      animals.
AB  - Intestinal nutrient infusions result in variable decreases in food intake and
      body weight based on the nutrient type and the specific intestinal infusion site.
      We previously found that intrajejunal infusions of a fatty acid and glucose, but
      not casein hydrolysate, decreases food intake and body weight in lean chow-fed
      laboratory rats. To test whether obese, high fat-fed animals would show similar
      decreases in food intake and body weight in response to intrajejunal infusions of
      the same nutrients, equal kilocalorie loads of these nutrients (11.4 kcal) or
      vehicle were infused into the jejunum of obese, high fat-fed male Sprague-Dawley
      rats over 7 h/day for 5 consecutive days. Food intake was continuously monitored,
      and body weight was measured daily. After the infusion on the final day, rats
      were killed and plasma was collected. Similar to lean chow-fed rats, intrajejunal
      infusions of linoleic acid (LA) and glucose (Glu), but not casein hydrolysate
      (Cas), suppressed food intake with no compensatory increase in food intake after
      the infusion period. In contrast to lean chow-fed rats, only the LA, and not the
      Glu or Cas, produced decreases in body weight in the obese high fat-fed rat.
      There also were no differences in plasma glucagon-like peptide-1 levels in any of
      the nutrient infusion groups compared with saline infusion. These results suggest
      that there is a differential response to the same nutrients in lean vs. obese
      animals.

PMID- 24452548
TI  - Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han
      population of Northern China?
AB  - Papillary thyroid carcinoma (PTC) is one of the most common tumors of the thyroid
      gland. The common risk factors of PTC include ionizing radiation, positive family
      history, and thyroid nodular disease. PTC was identified in Europeans by
      conducting a genome-wide association study, and a strong association signal with
      PTC was observed in rs944289 and NKX2-1 (located at the 14q13.3 locus), which was
      probably the genetic risk factor of PTC. This study aimed to examine the
      association of this gene with PTC in Chinese. A total of 354 patients with PTC
      and 360 healthy control subjects from the Han population of Northern China were
      recruited in the study. These individuals were genotyped to determine rs12589672,
      rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was
      obtained (C vs. T, P = 0.027, OR = 1.264, 95% CI = 1.026 - 1.557; and C/C - C/T
      vs. T/T, P = 0.034, OR = 1.474, 95% CI = 1.028 - 2.112). Conducting a subgroup
      analysis, we found a marginal difference in the allele frequency distribution of
      rs944289 (adjusted P = 0.062) between the patients with PTC and multi-nodular
      goiter and the control subjects. We also observed an interaction (P = 0.029; OR =
      2.578, 95% CI = 1.104 - 6.023) between rs944289 and diabetes in patients with
      PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the
      Han population of Northern China, but no clear association was observed in either
      of the tag single nucleotide polymorphisms of NKX2-1.

PMID- 24452549
TI  - Nicotine gum or patch treatment for smoking cessation and smoking reduction: a
      multi-centre study in Chinese physicians.
AB  - In China, around 23% of physicians (41% male, 3% female) currently smoke.
      Pharmacotherapy for tobacco dependence is available, but is not widely used in
      China. The purpose of this study was to estimate the effectiveness and the safety
      on smoking cessation of nicotine gum and nicotine patch in Chinese healthcare
      professionals. Three hundred regular smokers motivated to quit were recruited
      from six hospitals in China. All subjects were accepted nicotine replacement
      therapy, and they could choose nicotine gum (2 mg or 4 mg, depending on baseline
      smoking level) or nicotine patch (15 mg/16 h) for 12 weeks, with a 12-week follow
      up. Limited behavioural support was provided. At Week 24, the 2-24 weeks
      continuous abstinence rate (verified by expired carbon monoxide) was 17%, the
      point prevalence abstinence rate (no smoking since the previous visit) was 35%,
      and 38% of subjects had continuously reduced their daily cigarette consumption by
      at least 50% versus baseline. Compliance with treatment was good, particularly
      with patch. No serious adverse event was reported, and most adverse events were
      mild or moderate. The most common treatment-related adverse events were
      gastrointestinal (both gum and patch) and local irritation symptoms. Nicotine
      patch and gum were well tolerated in Chinese smokers. Abstinence rates were
      comparable to those previously reported with nicotine replacement therapy, and
      many smokers who did not quit substantially reduced their cigarette consumption. 

PMID- 24452550
TI  - Regulation and function of histone acetyltransferase MOF.
AB  - The mammalian MOF (male absent on the first), a member of the MYST (MOZ, YBF2,
      SAS2, and Tip60) family of histone acetyltransferases (HATs), is the major enzyme
      that catalyzes the acetylation of histone H4 on lysine 16. Acetylation of K16 is
      a prevalent mark associated with chromatin decondensation. MOF has recently been
      shown to play an essential role in maintaining normal cell functions. In this
      study, we discuss the important roles of MOF in DNA damage repair, apoptosis, and
      tumorigenesis. We also analyze the role of MOF as a key regulator of the core
      transcriptional network of embryonic stem cells. 

PMID- 24452551
TI  - The quiet revolutionary.

PMID- 24452552
TI  - Why continuity matters: Ian McWhinney's insights for 21st-century medical
      education.

PMID- 24452553
TI  - From clinical observation to clinical discovery: the challenge for family
      medicine research.

PMID- 24452554
TI  - What would an Ian McWhinney health care system look like?

PMID- 24452555
TI  - The gentle radical: ten reflections on Ian McWhinney, generalism, and family
      medicine today.

PMID- 24452556
TI  - Instructional video on vasectomy: evidence-based procedure should be
      demonstrated.

PMID- 24452557
TI  - Lower treatment thresholds.

PMID- 24452558
TI  - Hot yoga and pregnancy: fitness and hyperthermia.
AB  - QUESTION: One of my pregnant patients wishes to continue her hot yoga exercises
      during pregnancy. Is this practice safe? ANSWER: With the increased risk of
      neural tube defects and possibly of other malformations among fetuses exposed to
      excessive heat, pregnant women should avoid practising hot yoga during pregnancy.

PMID- 24452559
TI  - Antihistamines for children with otitis media.
AB  - QUESTION: Otitis media is a very common condition in pediatrics and can be quite
      distressing for children and their parents. Is there a role for antihistamines
      and decongestants in the management of acute otitis media orotitis media with
      effusion in children? ANSWER: Traditionally, antihistamines and decongestants
      have been used in the treatment of otitis media;however, recent guidelines, which
      are based on study findings with negative results, recommend against routine use.
      No antihistamine-decongestant combination has been shown to be of clinically
      significant benefit,and there are potential adverse events that need to be taken
      into account.

PMID- 24452561
TI  - Effectiveness of the trivalent influenza vaccine.

PMID- 24452560
TI  - Treatment of acute migraine in the emergency department.

PMID- 24452562
TI  - Mycobacterium fortuitum breast abscess after nipple piercing.

PMID- 24452563
TI  - Methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination
      continues to occur.

PMID- 24452564
TI  - Microscopic potassium hydroxide preparation.

PMID- 24452566
TI  - Telling stories about stories.

PMID- 24452565
TI  - Marathon maternity oral history project: Exploring rural birthing through
      narrative methods.
AB  - OBJECTIVE: To explore how birthing and maternity care are understood and valued
      in a rural community. DESIGN: Oral history research. SETTING: The rural community
      of Marathon, Ont, with a population of approximately 3500. PARTICIPANTS: A
      purposive selection of mothers, grandmothers, nurses, physicians, and community
      leaders in the Marathon medical catchment area. METHODS: Interviews were
      conducted with a purposive sample, employing an oral history research
      methodology. Interviews were conducted non-anonymously in order to preserve the
      identity and personhood of participants. Interview transcripts were edited into
      short narratives. Oral histories offer perspectives and information not revealed
      in other quantitative or qualitative research methodologies. Narratives re
      personalize and humanize medical research by offering researchers and
      practitioners the opportunity to bear witness to the personal stories affected
      through medical decision making. MAIN FINDINGS: Eleven stand-alone narratives,
      published in this issue of Canadian Family Physician, form the project's
      findings. Similar to a literary text or short story, they are intended for
      personal reflection and interpretation by the reader. Presenting the results of
      these interviews as narratives requires the reader to participate in the research
      exercise and take part in listening to these women's voices. The project's
      narratives will be accessible to readers from academic and non-academic
      backgrounds and will interest readers in medicine and allied health professions,
      medical humanities, community development, gender studies, social anthropology
      and history, and literature. CONCLUSION: Sharing personal birthing experiences
      might inspire others to reevaluate and reconsider birthing practices and services
      in other communities. Where local maternity services are under threat, Marathon's
      stories might contribute to understanding the meaning and challenges of local
      birthing, and the implications of losing maternity services in rural Canada.

PMID- 24452567
TI  - Fledgling.

PMID- 24452568
TI  - Little things matter.

PMID- 24452569
TI  - Jeffrey Sirzyk MD CCFP(EM) FCFP.

PMID- 24452570
TI  - Facilitating informed consent for EMR research in Quebec.

PMID- 24452571
TI  - Video review: communication skills-oriented approach for community preceptors.

PMID- 24452572
TI  - An exciting time of year.

PMID- 24452573
TI  - Nurturing curiosity and making an impact.

PMID- 24452575
TI  - Patient-reported access to primary care in Ontario: effect of organizational
      characteristics.
AB  - OBJECTIVE: To describe patient-reported access to primary health care across 4
      organizational models of primary care in Ontario, and to explore how access is
      associated with patient, provider, and practice characteristics. DESIGN: Cross
      sectional survey. SETTING: One hundred thirty-seven randomly selected primary
      care practices in Ontario using 1 of 4 delivery models (fee for service,
      established capitation, reformed capitation, and community health centres).
      PARTICIPANTS: Patients included were at least 18 years of age, were not severely
      ill or cognitively impaired, were not known to the survey administrator, had
      consenting providers at 1 of the participating primary care practices, and were
      able to communicate in English or French either directly or through a translator.
      MAIN OUTCOME MEASURES: Patient-reported access was measured by a 4-item scale
      derived from the previously validated adult version of the Primary Care
      Assessment Tool. Questions were asked about physician availability during and
      outside of regular office hours and access to health information via telephone.
      Responses to the scale were normalized, with higher scores reflecting greater
      patient-reported access. Linear regressions were used to identify characteristics
      independently associated with access to care. RESULTS: Established capitation
      model practices had the highest patient-reported access, although the difference
      in scores between models was small. Our multilevel regression model identified
      several patient factors that were significantly (P = .05) associated with higher
      patient-reported access, including older age, female sex, good-to-excellent self
      reported health, less mental health disability, and not working. Provider
      experience (measured as years since graduation) was the only provider or practice
      characteristic independently associated with improved patient-reported access.
      CONCLUSION: This study adds to what is known about access to primary care. The
      study found that established capitation models outperformed all the other
      organizational models, including reformed capitation models, independent of
      provider and practice variables save provider experience. This suggests that the
      capitation models might provide better access to care and that it might take time
      to realize the benefits of organizational reforms.

PMID- 24452574
TI  - Patient-specific academic detailing for smoking cessation: feasibility study.
AB  - OBJECTIVE: To describe and to determine the feasibility of a patient-specific
      academic detailing (PAD) smoking cessation (SC) program in a primary care
      setting. DESIGN: Descriptive cohort feasibility study. SETTING: Hamilton, Ont.
      PARTICIPANTS: Pharmacists, physicians, nurse practitioners, and their patients.
      INTERVENTIONS: Integrated pharmacists received basic academic detailing training
      and education on SC and then delivered PAD to prescribers using structured verbal
      education and written materials. Data were collected using structured forms. MAIN
      OUTCOME MEASURES: Five main feasibility criteria were generated based on Canadian
      academic detailing programs: PAD coordinator time to train pharmacists less than
      40 hours; median time of SC education per pharmacist less than 20 hours; median
      time per PAD session less than 60 minutes for initial visit; percentage of
      prescribers receiving PAD within 3 months greater than 50%; and number of new SC
      referrals to pharmacists at 6 months more than 10 patients per 1.0 full-time
      equivalent (FTE) pharmacist (total of approximately 30 patients). RESULTS: Eight
      pharmacists (5.8 FTE) received basic academic detailing training and education on
      SC PAD. Forty-eight physicians and 9 nurse practitioners consented to participate
      in the study. The mean PAD coordinator training time was 29.1 hours. The median
      time for SC education was 3.1 hours. The median times for PAD sessions were 15
      and 25 minutes for an initial visit and follow-up visit, respectively. The
      numbers of prescribers who had received PAD at 3 and 6 months were 50 of 64
      (78.1%) and 57 of 64 (89.1%), respectively. The numbers of new SC referrals at 3
      and 6 months were 11 patients per FTE pharmacist (total of 66 patients) and 34
      patients per FTE pharmacist (total of 200 patients), respectively. CONCLUSION:
      This study met the predetermined feasibility criteria with respect to the
      management, resources, process, and scientific components. Further study is
      warranted to determine whether PAD is more effective than conventional academic
      detailing.

PMID- 24452576
TI  - Improving delivery of primary care for vulnerable migrants: Delphi consensus to
      prioritize innovative practice strategies.
AB  - OBJECTIVE: To identify and prioritize innovative strategies to address the health
      concerns of vulnerable migrant populations. DESIGN: Modified Delphi consensus
      process. SETTING: Canada. PARTICIPANTS: Forty-one primary care practitioners,
      including family physicians and nurse practitioners, who provided care for
      migrant populations. METHODS: We used a modified Delphi consensus process to
      identify and prioritize innovative strategies that could potentially improve the
      delivery of primary health care for vulnerable migrants. Forty-one primary care
      practitioners from various centres across Canada who cared for migrant
      populations proposed strategies and participated in the consensus process. MAIN
      FINDINGS: The response rate was 93% for the first round. The 3 most highly ranked
      practice strategies to address delivery challenges for migrants were language
      interpretation, comprehensive interdisciplinary care, and evidence-based
      guidelines. Training and mentorship for practitioners, intersectoral
      collaboration, and immigrant community engagement ranked fourth, fifth, and
      sixth, respectively, as strategies to address delivery challenges. These
      strategies aligned with strategies coming out of the United States, Europe, and
      Australia, with the exception of the proposed evidence-based guidelines.
      CONCLUSION: Primary health care practices across Canada now need to evolve to
      address the challenges inherent in caring for vulnerable migrants. The selected
      strategies provide guidance for practices and health systems interested in
      improving health care delivery for migrant populations.

PMID- 24452577
TI  - Thanks, Dad.

PMID- 24452578
TI  - Penny Armitage: "I'm the 85th baby born in Marathon": Narrative 1 of the Marathon
      maternity oral history project. Interview date: August 14, 2008.

PMID- 24452579
TI  - Jennifer Coleman: "I deliver babies with the docs": Narrative 2 of the Marathon
      maternity oral history project. Interview date: August 11, 2008.

PMID- 24452580
TI  - Nancy Fitch: "Humanity isn't machines, you know": Narrative 3 of the Marathon
      maternity oral history project. Interview date: August 12, 2008.

PMID- 24452581
TI  - Jillian McPeake: "Look at that face!": Narrative 4 of the Marathon maternity oral
      history project. Interview date: August 21, 2008.

PMID- 24452582
TI  - Cheryl McWatch: "If you do it right, you'll feel it in your heart": Narrative 5
      of the Marathon maternity oral history project. Interview date: August 21, 2008.

PMID- 24452583
TI  - Connie McWatch: "I have a lot of blessings": Narrative 6 of the Marathon
      maternity oral history project. Interview date: August 12, 2008.

PMID- 24452584
TI  - Physician surveillance of influenza: collaboration between primary care and
      public health.
AB  - PROBLEM ADDRESSED: Influenza-like illness (ILI) is a global and national concern.
      The surveillance of ILI requires collaborative efforts from many diverse
      settings, including primary care clinics. OBJECTIVE OF PROGRAM: To develop a
      sustainable reporting mechanism that enables primary care practices to provide
      ILI surveillance information to public health (PH) and addresses the needs of
      primary care practices and PH. PROGRAM DESCRIPTION: An automated, electronic ILI
      reporting program that collects information on ILI activity directly from family
      physicians; the program is integrated with the practice's electronic medical
      record (EMR) system and therefore does not require physician initiation or
      disrupt physician workflow. Surveillance information is collected from a random
      sample of patient encounters using an automated pop-up screen that appears when
      exiting the patient's EMR. Weekly summary reports are transmitted electronically
      to PH. CONCLUSION: The EMR-integrated physician ILI reporting program is a simple
      and inexpensive way for family physicians to provide PH with important real-time,
      community-level disease surveillance information that is both complete and
      accurate. The program has been used in Hamilton, Ont, since 2004, which clearly
      demonstrates that it is a feasible and sustainable program in practice.

PMID- 24452585
TI  - Marie Michano: "That sense of being at home": Narrative 7 of the Marathon
      maternity oral history project. Interview date: August 21, 2008.

PMID- 24452586
TI  - Tracy Michano-Stewart: "A lifestyle type of thing": Narrative 8 of the Marathon
      maternity oral history project. Interview date: August 18, 2008.

PMID- 24452587
TI  - Ada Parsons: "Giving birth should be a special time": Narrative 9 of the Marathon
      maternity oral history project. Interview date: August 22, 2008.

PMID- 24452588
TI  - Rupa Patel: "We straddle those worlds": Narrative 10 of the Marathon maternity
      oral history project. Interview date: November 22, 2008.

PMID- 24452589
TI  - Patti Pella: "Someone knows your life story": Narrative 11 of the Marathon
      maternity oral history project. Interview date: August 22, 2008.

PMID- 24452590
TI  - Improvement in asthma control and inflammation in children undergoing
      adenotonsillectomy.
AB  - BACKGROUND: Observational studies suggest that asthma control improves after
      adenotonsillectomy, but longitudinal studies that correlate the effect of the
      procedure on the levels of biomarkers associated with airway inflammation are
      limited. METHODS: We conducted a longitudinal, observational study on pediatric
      patients, both with and without asthma, undergoing adenotonsillectomy. Asthma
      control test (ACT) scores and chitinase activity in the circulation were measured
      at time of surgery and at 6-mo follow-up. RESULTS: Sixty-six children with asthma
      and 64 control subjects were enrolled. Mean ACT scores improved by three points
      (P < 0.001) after 6 mo. 85% of children with poorly controlled asthma
      demonstrated an increase in ACT score of at least three points or a decrease in
      emergency department/urgent care visits, oral corticosteroid courses, or rescue
      short acting bronchodilator usage. Chitinase activity decreased significantly in
      asthmatics who improved (P < 0.01). Higher chitinase activity levels at baseline
      were associated with improved asthma control following surgery (P < 0.01).
      CONCLUSION: In children with high preoperative circulating chitinase activity
      levels, asthma control and healthcare utilization were significantly improved
      after adenotonsillecotmy. Chitinase activity decreased after surgery in children
      with improved control. This suggests that adenotonsillectomy modulates chitinase
      activity, affecting airway inflammation and improving airway disease.

PMID- 24452591
TI  - Impact of maternal overnutrition on gluconeogenic factors and methylation of the
      phosphoenolpyruvate carboxykinase promoter in the fetal and postnatal liver.
AB  - BACKGROUND: Exposure to maternal obesity or hyperglycemia increases the risk of
      obesity and poor glucose tolerance in the offspring. We hypothesized that
      maternal overnutrition in late pregnancy would result in (i) lower methylation in
      the promoter region of the cytosolic form of phosphoenolpyruvate carboxykinase
      (PEPCK-C; PCK1) and (ii) higher expression of hepatic gluconeogenic factors in
      the fetal and postnatal lamb. METHODS: Ewes were fed 100% (n = 18) or ~155% (n =
      17) of energy requirements from 115 d gestation, and livers were collected at
      ~140 d gestation or 30 d postnatal age. RESULTS: Maternal overnutrition resulted
      in a decrease in hepatic expression of the mitochondrial form of PEPCK (PEPCK-M;
      PCK2) but not of PEPCK-C or glucose-6-phosphatase (G6PHOS) before and after
      birth. Hepatic expression of peroxisome proliferator-activated receptor gamma
      coactivator 1 (PGC-1), peroxisome proliferator-activated receptor alpha
      (PPARalpha), PEPCK-C, G6PHOS, and 11beta hydroxysteroid dehydrogenase type 1
      (11betaHSD1), but not PEPCK-M, was higher in the postnatal lamb compared with
      that in the fetal lamb. The level of PCK1 methylation was paradoxically
      approximately twofold higher in the postnatal liver compared with that in the
      fetal liver. CONCLUSION: Maternal overnutrition programs a decrease in hepatic
      PEPCK-M in the offspring and as ~50% of total hepatic PEPCK is PEPCK-M, the
      longer-term consequences of this decrease may be significant.

PMID- 24452592
TI  - Nonfunctioning pituitary adenomas: association of Ki-67 and HMGA-1 labeling
      indices with residual tumor growth.
AB  - BACKGROUND: The postoperative biological behavior of nonfunctioning pituitary
      adenomas (NFPAs) is variable. Some residual NFPAs are stable long-term, others
      grow, and some recur despite complete removal. The usual histological markers of
      tumor aggressiveness are often similar between recurring, regrowing, and stable
      tumors, and therefore are not reliable as prognostic parameters. In this study,
      the clinical utility of proliferation indices (labeling index, Li) based on
      immunohistochemistry targeted at antigens Ki-67 and High-mobility group A1 (HMGA
      1) for prediction of NFPA prognosis was investigated. METHODS: Fifty patients
      with NFPAs were investigated. In each patient, Ki-67 and HMGA-1 Li were
      evaluated. Based on postoperative magnetic resonance images, patients were
      classified as tumor-free (18 patients), or harboring a residual tumor (32
      patients). The latter group was further subdivided into groups with stable tumor
      remnants (11 patients) or progressive tumor remnants (21 patients). RESULTS: The
      median follow-up period was 8 years. No significant relationship between HMGA-1
      Li and residual tumor growth was found. Growing residual tumors showed a trend
      towards higher Ki-67 Li compared with stable ones (p = 0.104). All tumor remnants
      with Ki-67 Li above 2.2% were growing. The relationship between residual tumor
      growth and Ki-67 Li exceeding the cutoff value of 2.2% was significant (p = 0.01
      in univariate, p = 0.044 in multivariate analysis). CONCLUSIONS: The prognostic
      significance of the HMGA-1 antigen was not confirmed. In contrast, the Ki-67 Li
      provides useful and valuable information for the postoperative management of
      NFPAs. In residual adenomas with a Ki-67 Li above 2.2%, regrowth should be
      expected, and these tumors may require shorter intervals of follow-up magnetic
      resonance imaging (MRI) and/or early adjuvant therapy. Future larger studies are
      needed to confirm the results of this study.

PMID- 24452593
TI  - Improvement in intraoperative transcranial electrical motor-evoked potentials in
      tethered cord surgery: an analysis of 45 cases.
AB  - BACKGROUND: Improvement of transcranial electrical motor-evoked potentials
      (TeMEPs) following untethering during tethered cord surgery (TCS) and its
      clinical significance have not been analyzed in the literature. METHODS: Forty
      five consecutive cases of tethered cord were operated on with multimodality
      intraoperative neurophysiological monitoring (IONM) between February 2005 and
      January 2012. Intraoperative TeMEP change was classified as improvement,
      worsening or no change. Motor, sensory, bladder and bowel symptoms and signs were
      evaluated preoperatively, in the first week post-surgery and at the last follow
      up (maximum of 2 years). RESULTS: Patient age ranged from 5 to 44 years (mean, 16
      +/- 10 years), with 30 children. Intraoperative MEPs improved in 23 (51 %),
      remained the same in 21 (46.7 %) and worsened in 1 (2 %) patient. Motor
      improvement occurred in 7 patients and clinical improvement in 17 patients in the
      immediate postoperative period. Postoperative neurological worsening occurred in
      one patient (2.2 %). Improved and stable MEPs correlated with the motor (p =
      0.002) and clinical improvement (p = 0.02) in the immediate postoperative period.
      Follow-up was available in 35 patients (77.7 %), ranging from 5 to 24 months
      (median, 21 months; mean, 17.7 +/- 6.8 months). There was late clinical
      improvement in 73.5 % of the patients in whom the intraoperative MEP had remained
      the same or improved. However, there was no statistically significant correlation
      between MEP change and long-term outcome. CONCLUSIONS: Intraoperative MEP
      improvement occurs in about 50 % of the patients following successful
      untethering. This finding probably provides support to the ischemic theory of
      tethered cord syndrome.

PMID- 24452594
TI  - The persistent crucial role of the left hemisphere for language in left-handers
      with a left low grade glioma: a stimulation mapping study.
AB  - BACKGROUND: Left-handers have a more bilateral language representation than right
      handers. Therefore, in left-handers with a low-grade glioma (LGG) in the left
      hemisphere (LH), one could hypothesize that the right hemisphere (RH) might allow
      language compensation, at least partly, with no or only a minor persistent role
      of the LH in speech. However, although LGG induces language reorganization in
      right-handed patients, little is known in left-handers. Here, we report the first
      series of left-handers who underwent awake surgery for a left LGG using
      intraoperative mapping, in order to investigate whether there was still an
      involvement of LH in language. METHOD: Ten consecutive left-handed patients were
      operated for a left LGG (three frontal, four paralimbic, one parietal, one
      temporal, one parieto-temporal tumor) using an awake procedure with
      intraoperative electrical language mapping. RESULTS: Intraoperative language
      disorders were elicited in all cases but one by electrostimulation in the LH.
      Cortical language sites were detected in nine cases. Subcortical stimulation also
      demonstrated the crucial role of left white matter pathways in language,
      including the inferior occipital-frontal fascicle, arcuate fascicle, lateral
      segment of the superior longitudinal fascicle and fibers from the ventral
      premotor cortex. Moreover, stimulation of deep gray nuclei generated language
      disturbances in four patients. These nine patients experienced transient
      postoperative language worsening, supporting the persistent critical role of LH
      in speech. In only one patient, no language deficit was evoked intraoperatively
      and postoperatively. The ten patients returned to a normal life. Total or
      subtotal resection was achieved in all cases but one. CONCLUSIONS: Our results
      suggest that, even though the RH may participate in language compensation, the LH
      in left-handers still plays a crucial role, despite a left slow-growing LGG.
      Thus, we propose to routinely consider awake surgery for left LGG removal in left
      handers patients, to optimize the extent of resection while preserving language.

PMID- 24452596
TI  - Cobalt selenium oxohalides: catalysts for water oxidation.
AB  - Two new oxohalides Co4Se3O9Cl2 and Co3Se4O10Cl2 have been synthesized by solid
      state reactions. They crystallize in the orthorhombic space group Pnma and the
      monoclinic space group C2/m respectively. The crystal structure of the two
      compounds are made up of similar building blocks; Co4Se3O9Cl2 is made up of
      [CoO4Cl2], [CoO5Cl] and [SeO3] polyhedra and Co3Se4O10Cl2 is made up of [CoO4Cl2]
      and [SeO3] polyhedra. As several Co-containing compounds have proved to be good
      catalysts for water oxidation, the activities of the two new compounds were
      compared with the previously found oxohalide Co5Se4O12Cl2 in reference to CoO and
      CoCl2. The one electron oxidant Ru(bpy)3(3+) was used as oxidizing species in a
      phosphate buffer and it was found that the activities of the oxohalide species
      were in between CoO and CoCl2. The roles of Cl(-) and PO4(3-) ions are discussed.

PMID- 24452595
TI  - E3 ubiquitin ligase Cullin4B mediated polyubiquitination of p53 for its
      degradation.
AB  - Controlled protein ubiquitination through E3 ubiquitin ligases and degradation
      via 26S proteasome machinery is required for orderly progression through cell
      cycle, chromatin remodeling, DNA repair, and development. Each cullin-dependent
      ubiquitin ligase (E3) complex can recruit various substrates for their
      degradation. Cullin 4A (CUL4A) and Cullin 4B (CUL4B) are members of cullin family
      proteins that mediate ubiquitin dependent proteolysis. Though, these two cul4
      genes are functionally redundant, Cullin 4B is not a substitute for all the
      Cullin 4A functions. Published report has shown that CUL4A interacts with p53 and
      induces its decay. Although, CUL4A has been known to control several cellular
      processes, little is known about CUL4B functions. Therefore, in this study, we
      analyzed the role of CUL4B on p53 polyubiquitination. Our stable cell line and
      transient transfection studies show that CUL4B indeed interacts with p53 and
      induces its polyubiquitination. Importantly, both CUL4A and CUL4B overexpressing
      cells show almost equal levels of p53 polyubiquitination. Moreover, we observed
      an increased level of polyubiquitination on p53 in CUL4B overexpressing stable
      cell line upon treatment with siRNA specific for CUL4A indicating that CUL4B
      plays a vital role in p53 stability. In addition, we have observed the
      differential expression of CUL4B in various eukaryotic cell lines and mouse
      tissues suggesting the important role of CUL4B in various tissues. Together,
      these observations establish an important negative regulatory role of CUL4B on
      p53 stability.

PMID- 24452597
TI  - Downregulation of microRNA-26a is associated with metastatic potential and the
      poor prognosis of osteosarcoma patients.
AB  - Accumulating evidence indicates that microRNAs are involved in multiple processes
      in cancer development and progression. microRNA-26a (miR-26a) has been identified
      as a tumor suppressor and its downregulation is associated with poor prognosis in
      several types of human cancer. However, the specific function of miR-26a in
      osteosarcoma remains unclear. In the present study, we found that the expression
      of miR-26a in osteosarcoma tissues and cell lines was much lower than that in the
      normal controls, respectively. In addition, downregulation of miR-26a more
      frequently occurred in osteosarcoma specimens with adverse clinical stage and
      with the presence of distant metastasis. Moreover, multivariate survival analyses
      demonstrated that loss of miR-26a is an independent prognostic factor for both
      disease-free and overall survival in osteosarcoma. In addition, restoration of
      miR-26a expression inhibited the invasion and migration in osteosarcoma cells,
      and miR-26a directly inhibited enhancer of zeste homolog 2 (EZH2) expression by
      targeting its 3'-UTR. Moreover, EZH2 was upregulated and inversely correlated
      with miR-26a expression in the osteosarcoma tissues. Thus, for the first time, we
      provide convincing evidence that downregulation of miR-26a is associated with
      tumor aggressiveness and tumor metastasis, and miR-26a inhibits cell migration
      and invasion by targeting the EZH2 gene in osteosarcoma. Thus, miR-26a is an
      independent prognostic marker for osteosarcoma patients.

PMID- 24452598
TI  - Temporary adjunctive cilostazol vs clopidogrel loading for ST-segment elevation
      acute myocardial infarction.
AB  - BACKGROUND: Clopidogrel loading is a standard method to achieve rapid platelet
      inhibition and prevent thrombotic events. At the current time, little information
      is available to determine the effect of adjunctive cilostazol compared with
      clopidogrel loading. METHODS: We retrospectively analyzed 212 patients undergoing
      primary percutaneous coronary intervention with drug-eluting stents for ST
      segment elevation acute myocardial infarction. All patients were administered
      aspirin (100 mg once a day) and clopidogrel (75 mg once a day). The patients were
      divided into two groups according to the presence (loading group, n = 100) or
      absence (cilostazol group, n = 112) of clopidogrel loading (300 mg). Patients in
      the cilostazol group were administered adjunctive cilostazol (100 mg twice a day)
      in place of clopidogrel loading. Patient characteristics, medications, and 30-day
      clinical outcomes were examined. RESULTS: The mean duration of cilostazol
      administration in the cilostazol group was 6.2 +/- 4.9 days from the time of
      primary coronary intervention. No significant difference was observed in major
      adverse cardiac events (cardiac death, definite stent thrombosis, and non-fatal
      myocardial infarction) between the loading group and the cilostazol group (9/100;
      9.0 vs. 8/112; 7.1%, p = 0.62). Definite stent thrombosis was observed for two
      patients in the loading group and one patient in the cilostazol group. The
      occurrence ratio of bleeding events did not differ significantly between the two
      groups (9.0 vs. 5.4%, p = 0.30). CONCLUSION: There was no significant difference
      in the incidence of major adverse cardiac events between temporary adjunctive
      cilostazol treatment and clopidogrel loading in ST-segment elevation acute
      myocardial infarction patients. Our findings suggest one potential of cilostazol.

PMID- 24452599
TI  - Heart rate reduction with ivabradine in patients with acute decompensated
      systolic heart failure.
AB  - INTRODUCTION: In patients with acute decompensated systolic heart failure (ADSHF)
      high resting heart rate (HR) could be either a compensatory mechanism or
      contribute to worsening heart failure. The aim of this study was to evaluate, in
      patients with ADSHF and resting HR >70 bpm, the early (within 24 h) and late (at
      discharge) effects of oral administration of ivabradine on HR reduction. METHODS:
      Ten consecutive patients with ADSHF, left ventricular ejection fraction <40 % and
      HR >70 bpm, without other acute conditions or inotropic therapy, began open-label
      treatment with oral ivabradine according to a pre-established Heart Failure Unit
      protocol. We obtained clinical and laboratory data at four periods: admission
      (T0), immediately before initiation of ivabradine (T2), 24 h after initiation of
      ivabradine (T3), and at discharge (T4). RESULTS: Ivabradine was administered in
      60 % of the patients before the second day. HR decreased 10.7 +/- 7.2 bpm at T3
      (p < 0.001) and 16.3 +/- 8.2 bpm at T4 (p = 0.002). The systolic blood pressure
      decreased at T3 (p = 0.012), returning to baseline values at T4. There was no
      change in diastolic and mean blood pressure. New York Heart Association (NYHA)
      class improvement by two levels was associated with lower HR at T4 (p = 0.033).
      HR and N-terminal pro-brain natriuretic peptide (Nt-ProBNP) at baseline
      correlated significantly [Spearman correlation coefficient (rs) = 0.789, p =
      0.013]. Total Nt-ProBNP reduction correlated with the HR before (r = 0.762, p =
      0.028) and after (T3: r = 0.647, p = 0.083; T4: r = 0.738, p = 0.037) ivabradine
      addition. CONCLUSION: In the present cohort of patients with ADSHF and HR >70
      bpm, the selective reduction of HR with oral ivabradine was safe and efficient.

PMID- 24452600
TI  - New oral anticoagulants in practice: pharmacological and practical
      considerations.
AB  - Although highly effective, warfarin use is complicated by its unpredictable
      narrow therapeutic window, genetic heterogeneity in pharmacokinetic response,
      numerous food and drug interactions, and the need for regular international
      normalized ratio (INR) monitoring. Currently, several novel oral anticoagulant
      (NOAC) drugs (dabigatran, rivaroxaban, apixaban) are available on the market as
      alternatives to warfarin. These agents all feature more predictable
      pharmacodynamic and pharmacokinetic properties than warfarin. Additionally, the
      NOACs do not require routine monitoring of coagulation parameters, and have a
      relatively lower potential for interactions with drug, herb, and dietary
      constituents, which enhances the convenience of management for both patients and
      health professionals alike. However, there are other considerations regarding the
      use of NOACs that must be taken into account during management of therapy. In
      contrast to warfarin, most NOACs need dosage adjustments in renal impairment and
      are contraindicated in severe liver impairment, and there are no specific
      antidotes for treating NOAC-related over-anticoagulation. The more frequent
      dosing needed for NOACs may reduce adherence, especially in elderly patients with
      polypharmacy. Furthermore, NOACs, especially dabigatran, are not as well
      tolerated as warfarin in patients with gastrointestinal diseases. Overall, the
      availability of the NOACs has expanded the treatment armamentarium, but they are
      not without risk. Given the limited experience with the NOACs, their limited
      range of indications, and their cost, the characteristics of each anticoagulant
      must be carefully considered to carefully select the agent that will provide the
      optimal risk/benefit profile in the individual patient.

PMID- 24452601
TI  - FOXO1-dependent DNA damage repair is regulated by JNK in lung cancer cells.
AB  - DNA damage or mutation in cells contributes to tumorigenesis. The transcription
      factor FOXO1 modulates the expression of genes involved in DNA damage repair,
      cell cycle arrest and apoptosis. The transcriptional activity of FOXO1 is
      fundamentally regulated by post-translational modification and subcellular
      localization. H1299 lung cancer cells were treated with the alkylating agent
      MNNG, and the cell viability and DNA damage were separately determined by MTT and
      comet assay. Using immunofluorescence and western blotting, we observed the
      subcellular localization of FOXO1 and measured the relevant protein expression
      levels, respectively. To examine cell cycle arrest and apoptosis, flow cytometry
      analysis was preformed. The interaction between FOXO1 and JNK was analyzed
      through immunoprecipitation. Our results showed that cell viability was reduced
      at 24 h after MNNG treatment, and appeared to recover to some degree at 48 h. The
      increased expression and nuclear export of FOXO1 emerged at 4 h after the
      treatment. Nuclear FOXO1 played a pivotal role in cell cycle arrest, apoptosis
      and DNA damage repair by upregulating p27(Kip1), Bim and GADD45 gene expression,
      respectively. AKT-dependent S256 phosphorylation of FOXO1 and the S473
      phosphorylation of AKT were both enhanced following DNA damage. Moreover, our
      studies revealed that FOXO1 directly interacted with JNK, and the inhibition of
      the JNK activity led to decreased expression of FOXO1 target genes. These
      findings suggest for the first time that FOXO1 is a promising candidate substrate
      for JNK, and the FOXO1-dependent DNA damage repair may be regulated positively by
      the JNK pathway in H1299 lung cancer cells.

PMID- 24452602
TI  - Bilateral internal thoracic artery grafting for peripheral arterial disease
      patients.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is known to have a poor prognosis.
      Some reports have also described poor late results after coronary artery bypass
      grafting (CABG). However, there have been few reports about whether bilateral
      internal thoracic artery grafting improves the long-term survival of PAD patients
      after CABG. We performed this study to clarify whether or not this is the case.
      METHODS: One hundred and thirty-six PAD patients who underwent elective CABG with
      two or more grafts were enrolled in this study. Patients were divided into two
      groups, 71 patients in the bilateral internal thoracic artery (BITA) group and 65
      patients in the single internal thoracic artery (SITA) group. The maximum follow
      up period was 19 years, with a mean of 5.7 +/- 4.4 years. RESULTS: We
      investigated the long-term results based on three factors; survival, freedom from
      cardiac death, and freedom from cardiac events. The 3-, 5- and 10-year survival
      rates in the BITA group were 83.0, 74.2, and 43.1%, respectively. And those in
      the SITA group were 79.4, 67.7, and 32.3%, respectively. There were no
      significant differences between the two groups (p = 0.5843). There were also no
      statistically significant differences between the two groups in terms of the
      freedom from cardiac death (p = 0.8589) or in the freedom from cardiac events (p
      = 0.9445). CONCLUSION: No long-term advantage was observed for CABG with BITA in
      comparison to SITA alone in patients with PAD.

PMID- 24452603
TI  - Staying the course: the option of doing nothing and its impact on postchoice
      persistence.
AB  - Individuals regularly face adversity in the pursuit of goals that require ongoing
      commitment. Whether or not individuals persist in the face of adversity greatly
      affects the likelihood that they will achieve their goals. We argue that a
      seemingly minor change in the individual's original choice set-specifically, the
      addition of a no-choice option-will increase persistence along the chosen path.
      Drawing on self-perception theory, we propose that choosing from a set that
      includes a no-choice (do nothing) option informs individuals that they both
      prefer the chosen path to other paths and that they consider this path alone to
      be worth pursuing, an inference that cannot be made in the absence of a no-choice
      option. This unique information strengthens individuals' commitment to, and
      increases their persistence on, their chosen path. Three studies employing
      incentive-compatible designs supported our predictions and ruled out several
      rival accounts. 

PMID- 24452604
TI  - Assessing "economic value": symbolic-number mappings predict risky and riskless
      valuations.
AB  - Diminishing marginal utility (DMU) is a basic tenet of economic and psychological
      models of judgment and choice, but its determinants are little understood. In the
      research reported here, we tested whether insensitivities in valuations of dollar
      amounts (e.g., $40, $100) may be due to inexact mappings of symbolic numbers
      (i.e., "40," "100") onto mental magnitudes. In three studies, we demonstrated
      that inexact mappings appear to guide valuation and mediate numeracy's relations
      with riskless valuations (Studies 1 and 1a) and risky choices (Study 2). The
      results highlight the fundamental notion that individuals' valuations of $100
      depend critically on how individuals perceive and map the symbolic quantity
      "100." This notion has implications for conceptualizations of value, risk
      aversion, intertemporal choice, and dual-process theories of decision making.
      Normative implications are also briefly discussed.

PMID- 24452605
TI  - Positive and negative correlations between confidence and accuracy for the same
      events in recognition of categorized lists.
AB  - Different researchers have reported positive, null, and negative relationships
      between confidence and accuracy in reports from memory. One possible reason for
      this paradox is the variety of materials used across experiments, but the two
      experiments reported in this article show that positive and negative confidence
      accuracy correlations can be observed using a single procedure and the same
      materials. Subjects studied words from semantic categories and then took a
      recognition test while making confidence ratings. For previously studied items,
      positive correlations between confidence and accuracy were obtained using three
      different measures. Yet when confidence-accuracy correlations were assessed for
      unstudied items from studied categories, the correlations were zero or negative.
      The critical factors in determining when negative correlations will be found are
      the similarity of lures to presented items and the type of analysis used. These
      results indicate that one should be cautious about relying on confidence of
      recognition when rememberers must decide among highly similar events. 

PMID- 24452606
TI  - The scent of disease: human body odor contains an early chemosensory cue of
      sickness.
AB  - Observational studies have suggested that with time, some diseases result in a
      characteristic odor emanating from different sources on the body of a sick
      individual. Evolutionarily, however, it would be more advantageous if the innate
      immune response were detectable by healthy individuals as a first line of defense
      against infection by various pathogens, to optimize avoidance of contagion. We
      activated the innate immune system in healthy individuals by injecting them with
      endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed
      individuals had a more aversive body odor relative to when they were exposed to a
      placebo. Moreover, this effect was statistically mediated by the individuals'
      level of immune activation. This chemosensory detection of the early innate
      immune response in humans represents the first experimental evidence that disease
      smells and supports the notion of a "behavioral immune response" that protects
      healthy individuals from sick ones by altering patterns of interpersonal contact.

PMID- 24452607
TI  - Mitochondrial lactate metabolism is involved in antioxidative defense in human
      astrocytoma cells.
AB  - Although lactate has traditionally been known to be an end product of anaerobic
      metabolism, recent studies have revealed its disparate biological functions.
      Oxidative energy production and cell signaling are two important roles assigned
      to this monocarboxylic acid. Here we demonstrate that mitochondrial lactate
      metabolism to pyruvate mediated by lactate dehydrogenase (LDH) in a human
      astrocytic cell line is involved in antioxidative defense. The pooling of this
      alpha-ketoacid helps to detoxify reactive oxygen species, with the concomitant
      formation of acetate. In-gel activity assays following blue native PAGE
      electrophoresis were utilized to demonstrate the increase in mitochondrial LDH
      activity coupled to the decrease in pyruvate dehydrogenase activity in the cells
      challenged by oxidative stress. The enhanced production of pyruvate with the
      concomitant formation of acetate in astrocytoma cells was monitored by high
      performance liquid chromatography. The ability of pyruvate to fend off oxidative
      stress was visualized by fluorescence microscopy with the aid of the dye 2',7'
      dichlorodihydrofluorescein diacetate. Immunoblotting helped confirm the presence
      of elevated levels of LDH in cells exposed to oxidative stress, and recovery
      experiments were performed with pyruvate to diminish the oxidative burden on the
      astrocytoma. The acetate, generated as a consequence of the antioxidative
      attribute of pyruvate, was subsequently channeled toward the production of
      lipids, a process facilitated by the upregulation in activity of acetyl-CoA
      synthetase and acetyl-CoA carboxylase, as demonstrated by in-gel activity assays.
      The mitochondrial lactate metabolism mediated by LDH appears to play an important
      role in antioxidative defence in this astrocytic system.

PMID- 24452608
TI  - Devices for mitral valve repair.
AB  - The natural history of severe mitral regurgitation (MR) is unfavorable, leading
      to left ventricular failure, atrial fibrillation, stroke, and death. Many
      patients affected by severe regurgitation (MR) do not currently undergo surgery,
      mainly due to the perceived risk of the procedure (old age, impaired left
      ventricular function, and comorbidities). Mitral transcatheter interventions
      carry the hope of minimizing risks while preserving clinical efficacy of surgical
      repair, as an alternative to conventional treatment. Multiple technologies and
      diversified approaches are under development with the purpose of treating MR in
      less invasive ways. They can be categorized based on the anatomical and patho
      physiological addressed target. Among them, MitraClip (Abbott Vascular, Inc.,
      Menlo Park, California) has emerged as a clinically safe and effective method for
      percutaneous mitral valve repair in patients either with degenerative and
      functional regurgitation. This device mimics the surgical edge-to-edge repair
      initially described by Alfieri in the early 1990s. Other repair technologies
      include percutaneous direct and indirect annuloplasty, neochordae implantation,
      and left ventricular reshaping. They are still in early phase clinical trials or
      preclinical studies. The combination of different repair techniques is likely to
      be required to achieve good long-lasting results. In the future, novel devices,
      improved knowledge, more efficient imaging, and transcatheter mitral prosthetic
      valve implantation may expand the indications to those patients currently not
      treated, as well as improve the results both in terms of early efficacy and long
      term durability. These treatments are currently reserved to high-risk and
      inoperable patients, and their application requires an integrated Heart-Team
      approach. They represent the natural evolution of surgery and promise to expand
      treatment options and improve patients' outcomes in the near future. 

PMID- 24452609
TI  - Cognitive impairment in chronic kidney disease: clinical findings, risk factors
      and consequences for patient care.
AB  - Cognitive deficits have a high prevalence in elderly patients with chronic kidney
      disease (CKD). The clinical picture consists of cognitive slowing, executive,
      memory and language deficits, and is attributed to cerebral white matter disease
      and clinically often silent brain infarcts. In the meantime, robust evidence
      exists that low estimated glomerular filtration rate, a measure of CKD severity,
      predisposes to cognitive deficits, cerebral white matter lesions, and ischemic
      brain infarcts in addition to demographic factors, vascular risk factors and
      diseases which also contribute to CKD-related cognitive deficits. In terminal
      CKD, cerebral blood flow is compromized during hemodialysis sessions, resulting
      in oxygen desaturation, cognitive deterioration and-in the longer run-brain
      atrophy. Kidney transplantation improves cognitive deficits in terminal CKD. At
      all stages, vascular risk factors and associated diseases should stringently be
      treated according to therapeutic guidelines. 

PMID- 24452610
TI  - New antithrombotics for secondary prevention of acute coronary syndrome.
AB  - Patients with acute coronary syndrome (ACS) usually receive acetylsalicylic acid
      plus an adenosine diphosphate (ADP) receptor inhibitor to reduce the long-term
      risk of recurrent events. However, patients receiving standard antiplatelet
      prophylaxis still face a substantial risk of recurrent events. Strategies
      involving 3 antithrombotic agents with different modes of action have now been
      tested. In Thrombin Receptor Antagonists for Clinical Event Reduction (TRA-CER),
      compared with standard care alone, bleeding complications including intracranial
      hemorrhage (ICH) were increased with the addition of vorapaxar, without efficacy
      benefit. In Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack
      and Stroke in Patients With Atherosclerosis (TRA 2 degrees P-TIMI 50), the
      addition of vorapaxar reduced recurrent events compared with standard care in
      stable patients with prior myocardial infarction. This study was terminated early
      in patients with prior stroke owing to excess ICH, though an increased risk of
      ICH or fatal bleeding was not detected in patients with prior myocardial
      infarction. The Apixaban for Prevention of Acute Ischemic and Safety Events 2
      (APPRAISE-2) trial of standard-dose apixaban added to standard care in patients
      with ACS was also stopped early owing to excess serious bleeding. However, in
      Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a
      Thienopyridine in Patients With Acute Coronary Syndromes (ATLAS ACS 2 TIMI 51),
      fatal bleeding or fatal ICH did not increase with low-dose rivaroxaban added to
      low-dose acetylsalicylic acid-based standard care compared with standard care
      alone. In that trial, a significant reduction of recurrent vascular events was
      shown with 3 antithrombotic regimens compared with standard care. Therefore,
      depending on drug dose and patient population, further reductions in recurrent
      vascular events after ACS may be possible in future clinical practice, with a
      favorable benefit-risk profile. 

PMID- 24452613
TI  - A B-C-N hybrid porous sheet: an efficient metal-free visible-light absorption
      material.
AB  - The polyphenylene network, known as porous graphene, is one of the most important
      and widely studied two-dimensional materials. As a potential candidate for
      photocatalysis and photovoltaic energy generation, its application has been
      limited by the low photocatalytic activity in the visible-light region. State-of
      the-art hybrid density functional theory investigations are presented to show
      that an analogous B-C-N porous sheet outperforms the pristine polyphenylene
      network with significantly enhanced visible-light absorption. Compared with
      porous graphene, the calculated energy gap of the B-C-N hybrid crystal shrinks to
      2.7 eV and the optical absorption peak remarkably shifts to the visible light
      region. The redox potentials of water splitting are well positioned in the middle
      of the band gap. Hybridizations among B_p, N_p and C_p orbitals are responsible
      for these findings. Valence and conduction band calculations indicate that the
      electrons and holes can be effectively separated, reducing charge recombination
      and improving the photoconversion efficiency. Moreover, the band gap and optical
      properties of the B-C-N hybrid porous sheet can be further finely engineered by
      external strain. 

PMID- 24452611
TI  - Erythrina abyssinica prevents meningoencephalitis in chronic Trypanosoma brucei
      brucei mouse model.
AB  - Human African trypanosomiasis is prevalent in Sub-sahara African countries that
      lie between 14 degrees  North and 29 degrees  south of the equator. Sixty million
      people are at risk of infection. Trypanosoma brucei gambesience occurs in West
      and Central Africa while Trypanosoma brucei rhodesience occurs in East and
      Southern Africa. The neurological stage of the disease is characterized by
      neuroinflammation. About 10% of patients treated with the recommended drug,
      melarsoprol develop post treatment reactive encephalopathy, which is fatal in 50%
      of these patients, thus melarsoprol is fatal in 5% of all treated patients. This
      study was aimed at establishing the potential activity of Erythrina abyssinica in
      reducing neuroinflammation following infection with Trypanosoma brucei brucei.
      Swiss white mice were divided into ten groups, two control groups and eight
      infected groups. Infected mice received either methanol or water extract of
      Erythrina abyssinica at 12.5, 25, 50 or 100 mg/kg body weight. Parasite counts
      were monitored in peripheral circulation from the third day post infection up to
      the end of the study. Brains were processed for histology, immunohistochemistry
      scanning and transmission electron microscopy. Following infection, trypanosomes
      were observed in circulation 3 days post-infection, with the parasitaemia
      occurring in waves. In the cerebrum, typical brain pathology of chronic
      trypanosomiasis was reproduced. This was exhibited as astrocytosis, perivascular
      cuffing and infiltration of inflammatory cells into the neuropil. However, mice
      treated with Erythrina abyssinica water extract exhibited significant reduction
      in perivascular cuffing, lymphocytic infiltration and astrocytosis in the
      cerebrum. The methanol extract did not have a significant difference compared to
      the non-treated group. This study provides evidence of anti-inflammatory
      properties of Erythrina abyssinica and may support its wide use as a medicinal
      plant by various communities in Kenya.

PMID- 24452612
TI  - Perioperative complications after live-donor hepatectomy.
AB  - Current studies of complications following donor hepatectomy may not be
      generalizable to all hospitals performing this procedure. To address this, live
      liver donors were identified in the Nationwide Inpatient Sample (2000-2008).
      Complications after donor hepatectomy were categorized using International
      Classification of Diseases, Ninth Revision codes and risk factors for
      complications were tested using logistic regression. Negative binomial regression
      models were used to estimate the increase in length of stay and hospital charge
      associated with complications. Among 555 donors (representing 2783 donors
      nationwide), 23% had 1 or more complications and 5% had a major complication. The
      most common complications were ileus (27%) and atelectasis (26%). No patient or
      hospital factors were associated with complications. Having any complication was
      associated with increased length of stay (incidence rate ratio, 1.36; 95% CI,
      1.16-1.58; P < .001) and hospital charge (incidence rate ratio, 1.25; 95% CI,
      1.09-1.44; P = .002). Approximately 25% of liver donors have complications
      immediately postoperatively but most are minor, lending support to current
      practices in live liver donation and donor selection.

PMID- 24452614
TI  - Identifying druggable targets by protein microenvironments matching: application
      to transcription factors.
AB  - Druggability of a protein is its potential to be modulated by drug-like
      molecules. It is important in the target selection phase. We hypothesize that:
      (i) known drug-binding sites contain advantageous physicochemical properties for
      drug binding, or "druggable microenvironments" and (ii) given a target, the
      presence of multiple druggable microenvironments similar to those seen previously
      is associated with a high likelihood of druggability. We developed DrugFEATURE to
      quantify druggability by assessing the microenvironments in potential small
      molecule binding sites. We benchmarked DrugFEATURE using two data sets. One data
      set measures druggability using NMR-based screening. DrugFEATURE correlates well
      with this metric. The second data set is based on historical drug discovery
      outcomes. Using the DrugFEATURE cutoffs derived from the first, we accurately
      discriminated druggable and difficult targets in the second. We further
      identified novel druggable transcription factors with implications for cancer
      therapy. DrugFEATURE provides useful insight for drug discovery, by evaluating
      druggability and suggesting specific regions for interacting with drug-like
      molecules.CPT: Pharmacometrics Systems Pharmacology (2014) 3, e93;
      doi:10.1038/psp.2013.66; published online 22 January 2014. 

PMID- 24452615
TI  - The pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of
      evacetrapib administered as monotherapy or in combination with statins.
AB  - Evacetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor
      currently being evaluated in a late-stage cardiovascular outcome trial. Using
      population-based models, we analyzed evacetrapib concentration data along with
      high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein
      cholesterol (LDL-C) data from a 12-week study in dyslipidemic patients treated
      with evacetrapib alone or in combination with atorvastatin, simvastatin, or
      rosuvastatin. Evacetrapib pharmacokinetics were characterized using a two
      compartment model with first-order absorption. Evacetrapib exposure increased in
      a less than dose-proportional manner, similar to other CETP inhibitors. No
      patient factors had a clinically relevant impact on evacetrapib pharmacokinetics.
      The relationships between evacetrapib exposure and HDL-C and LDL-C were
      characterized using Emax models. The theoretical maximal mean HDL-C increase and
      LDL-C decrease relative to baseline were 177 and 44.1%, respectively. HDL-C
      change from baseline was found to be negatively correlated with baseline HDL-C. A
      pharmacologically independent LDL-C reduction was found when evacetrapib was
      coadministered with statins.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e94;
      doi:10.1038/psp.2013.70; published online 22 January 2014. 

PMID- 24452616
TI  - Capturing drug responses by quantitative promoter activity profiling.

PMID- 24452618
TI  - Climbing a long hill: pelvic floor surgery and the need for geriatric
      urogynecology.

PMID- 24452619
TI  - Randomized clinical trial comparing TVT Secur system and trans vaginal obturator
      tape for the surgical management of stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: This prospective randomized study aimed to compare
      the safety and efficacy of the TVT-Secur (TVT-S) with the trans vaginal obturator
      tape (TVT-O) for the treatment of stress urinary incontinence. METHODS: We set
      out to enroll 136 patients in our study. 106 patients with stress urinary
      incontinence were randomized to either the TVT-S (n = 56) or TVT-O (n = 50)
      procedure. Patients were evaluated postoperatively at 2 months and 1 year. Our
      primary outcome was objective cure measured by the cough test. Secondary outcomes
      of subjective symptoms, questionnaires, pain scores, complications, and
      urodynamic studies were also included. Statistical analysis was by Chi-squared,
      Kruskal-Wallis, Wilcoxon, and Fisher's exact tests as appropriate. P values of
      <0.05 were considered significant. RESULTS: Objective cure rates were better for
      TVT-O compared with TVT-S at 1 year (86 % and 63 % respectively, p = 0.01).
      Subjective cure rates were 88 % for TVT-O and 63 % for TVT-S. Quality of life
      scores through questionnaires improved in both groups and were not statistically
      different. Initial post-operative groin pain was more prevalent in the TVT-O
      group; however, this resolved quickly with time. CONCLUSION: TVT-O was superior
      to TVT-S in the objective cure of stress urinary incontinence at 1-year follow
      up.

PMID- 24452620
TI  - Biomechanics of the rat vagina during pregnancy and postpartum: a 3-dimensional
      ultrasound approach.
AB  - INTRODUCTION AND HYPOTHESIS: The vagina and surrounding structures have been
      shown to remodel during pregnancy. Our objective was to characterize the
      biomechanical properties of the vagina in the rodent model in vivo utilizing
      three-dimensional (3D) ultrasound. METHODS: The vagina was visualized by
      ultrasound after distention by increasing pressures throughout pregnancy (15 and
      18 days) and after vaginal delivery (7 and 30 days postpartum) of six
      longitudinally followed rodents. The pelvic floor compliance and vaginal cross
      sectional area of the proximal, middle, and distal vagina were compared with
      those of nulliparous control animals (n = 8). RESULTS: The compliance of the
      pelvic floor increased 3.5- and 5.4-fold at days 15 and 18 of pregnancy
      respectively (p < 0.05). The compliance of the pelvic floor decreased 7 days
      postpartum, and it continued to decrease after vaginal delivery through the 30
      day time point. Using 3D ultrasound, we could characterize the remodeling of the
      vagina throughout pregnancy and after vaginal delivery. We could reconstruct the
      vaginal wall cross-sectional area and found the distal vaginal wall throughout
      pregnancy to be distended more than the proximal and middle regions. CONCLUSIONS:
      The observed changes in vaginal area may improve our understanding of which areas
      are at risk of injury during delivery. Further, 3D ultrasound allowed the
      determination of the in vivo biomechanical properties of the vagina. This image
      modality is beneficial for characterizing the in vivo properties of the vagina
      and surrounding pelvic support longitudinally within an animal.

PMID- 24452621
TI  - Catherine DeAngelis: Would like forgiveness from her patients.

PMID- 24452622
TI  - Early management of head injury: summary of updated NICE guidance.

PMID- 24452623
TI  - Beware the lies of patients.

PMID- 24452624
TI  - Homeopaths will be allowed to practise modern medicine in Maharashtra after one
      year pharmacology course.

PMID- 24452625
TI  - Romanian health system is in crisis as doctors leave for better working life.

PMID- 24452626
TI  - After period of failure, NHS regulator is now fit for purpose, say MPs.

PMID- 24452627
TI  - Presumed safe no more: lessons from the Wingspan saga on regulation of devices.

PMID- 24452628
TI  - Amyloid and tau in the brain in sporadic Alzheimer's disease: defining the
      chicken and the egg.

PMID- 24452629
TI  - Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA
      expression and chromosomal instability in primary intracranial pure germinomas.
AB  - Intracranial germ cell tumors (iGCTs) are the second most common brain tumors
      among children under 15 in Japan. The pathogenesis of iGCTs is largely
      unexplored. Although a subset of iGCTs is known to have KIT mutation, its impact
      on the biology and patients' survival has not been established. In this study, we
      investigated genes involved in the KIT signaling pathway. 65 iGCTs (30 pure
      germinomas, 14 teratomas, 18 mixed GCTs, 2 yolk sac tumors, 1 choriocarcinoma)
      were screened for mutation of KIT, KRAS, NRAS, HRAS, BRAF, PDGFRA, and IDH1 by
      direct sequencing. KIT expression was examined by immunohistochemistry and
      quantitative PCR. Chromosomal status was analyzed by array-comparative genomic
      hybridization (aCGH). Somatic mutations were detected only in KIT and RAS, which
      were frequently observed in pure germinomas (60.0 %), but rare in non
      germinomatous GCTs (NGGCTs) (8.6 %). All KIT/RAS mutations were mutually
      exclusive. Regardless of the mutation status or mRNA expression, the KIT protein
      was expressed in all germinomas, while only in 54.3 % of NGGCTs. Amplification of
      KIT was found in one pure germinoma by aCGH. In pure germinomas, high expression
      of KIT mRNA was associated with the presence of KIT/RAS alterations and severe
      chromosomal instability. Our results indicate that alterations of the KIT
      signaling pathway play an important role in the development of germinomas. Pure
      germinomas may develop through two distinct pathogeneses: one with KIT/RAS
      alterations, elevated KIT mRNA expression and severe chromosomal instability, and
      the other through yet an unidentified mechanism without any of the above
      abnormalities. 

PMID- 24452630
TI  - Consenting to sexual activity: the development and psychometric assessment of
      dual measures of consent.
AB  - Sexual assault prevention efforts have focused on educating students to obtain
      consent as a mechanism to reduce sexual assault, yet little is known about how
      college students consent to sex. Additionally, there are currently no measures
      available to assess students' consent to sex. The current study aimed to better
      understand college students consent by using a systematic approach to develop
      validated measures of sexual consent. This study integrated mixed methods via
      three phases and two waves of data collection to develop two measures of consent.
      In Phase 1, qualitative data were collected from college students (n = 185) to
      inform the design of quantitative measures aimed at assessing sexual consent at
      last sexual intercourse. In Phase 2, items were written for the closed-ended
      quantitative instrument and reviewed by a team of experts, educators, and
      clinicians. In Phase 3, a quantitative survey was administered to college
      students (n = 660) which included the measures of consent developed from the
      Phase 1 data; the measures were assessed for their psychometric properties.
      Exploratory factor analyses were utilized to assess the measures and resulted in
      five factors each for both consent scales. Both scales had high internal
      consistency reliability, showed gender differences, and showed differences across
      relationship status (single vs. in a relationship). The two newly developed
      measures assess unique constructs of consent and demonstrate assessments of
      specific concepts. Our findings provide an important contribution to the field of
      sexuality as these measures can be used in future research to better understand
      sexual consent.

PMID- 24452631
TI  - Sex-typed personality traits and gender identity as predictors of young adults'
      career interests.
AB  - Gender segregation of careers is still prominent in the U.S. workforce. The
      current study was designed to investigate the role of sex-typed personality
      traits and gender identity in predicting emerging adults' interests in sex-typed
      careers. Participants included 586 university students (185 males, 401 females).
      Participants reported their sex-typed personality traits (masculine and feminine
      traits), gender identities (gender typicality, contentment, felt pressure to
      conform, and intergroup bias), and interests in sex-typed careers. Results
      indicated both sex-typed personality traits and gender identity were important
      predictors of young adults' career interests, but in varying degrees and
      differentially for men and women. Men's sex-typed personality traits and gender
      typicality were predictive of their masculine career interests even more so when
      the interaction of their masculine traits and gender typicality were considered.
      When gender typicality and sex-typed personality traits were considered
      simultaneously, gender typicality was negatively related to men's feminine career
      interests and gender typicality was the only significant predictor of men's
      feminine career interests. For women, sex-typed personality traits and gender
      typicality were predictive of their sex-typed career interests. The level of
      pressure they felt to conform to their gender also positively predicted interest
      in feminine careers. The interaction of sex-typed personality traits and gender
      typicality did not predict women's career interests more than when these
      variables were considered as main effects. Results of the multidimensional
      assessment of gender identity confirmed that various dimensions of gender
      identity played different roles in predicting career interests and gender
      typicality was the strongest predictor of career interests. 

PMID- 24452632
TI  - User-identified gel characteristics: a qualitative exploration of perceived
      product efficacy of topical vaginal microbicides.
AB  - Research has demonstrated that certain vaginal gel products--microbicides
      containing antiretroviral drugs--may reduce HIV infection risk among women. But
      for vaginal gels to avert HIV and other sexually transmitted infections (STIs),
      at-risk women must be willing to use them as directed. These products must
      therefore be "acceptable" to women and an important component of acceptability is
      users' perception that the product will work to prevent infection. We sought to
      understand how women's perceptions of vaginal gel properties may shape their
      understanding of product efficacy for HIV and STI prevention. Sixteen women
      completed two in-depth qualitative interviews (k = 32) to identify the range and
      types of sensory perceptions they experienced when using two vaginal gels. We
      identified emergent themes and linkages between users' sensory perceptions and
      their beliefs about product efficacy. Users' predictions about product efficacy
      for preventing infection corresponded to measurable physical properties,
      including gel volume, location in the vagina, coating behavior, sensation of the
      gel in the vagina, leakage, and gel changes during coital acts. Although the
      women described similar sensory experiences (e.g., gel leaked from the vagina),
      they interpreted these experiences to have varying implications for product
      efficacy (e.g., leakage was predicted to increase or decrease efficacy). To
      improve microbicide acceptability, gel developers should investigate and
      deliberately incorporate properties that influence users' perceptions of
      efficacy. When a microbicide is approved for use, providers should educate users
      to anticipate and understand their sensory experiences; improving users'
      experience can maximize adherence and product effectiveness.

PMID- 24452633
TI  - Differential effects of bitter compounds on the taste transduction channels TRPM5
      and IP3 receptor type 3.
AB  - Transient receptor potential cation channel subfamily M member 5 (TRPM5) is a
      Ca(2+)-activated nonselective cation channel involved in the transduction of
      sweet, bitter, and umami tastes. We previously showed that TRPM5 is a locus for
      the modulation of taste perception by temperature changes, and by quinine and
      quinidine, 2 bitter compounds that suppress gustatory responses. Here, we
      determined whether other bitter compounds known to modulate taste perception also
      affect TRPM5. We found that nicotine inhibits TRPM5 currents with an effective
      inhibitory concentration of ~1.3mM at -50 mV. This effect may contribute to the
      inhibitory effect of nicotine on gustatory responses in therapeutic and
      experimental settings, where nicotine is often employed at millimolar
      concentrations. In addition, it implies the existence of a TRPM5-independent
      pathway for the detection of nicotine bitterness. Nicotine seems to act from the
      extracellular side of the channel, reducing the maximal whole-cell conductance
      and inducing an acceleration of channel closure that leads to a negative shift of
      the activation curve. TRPM5 currents were unaffected by nicotine's metabolite
      cotinine, the intensive sweetener saccharin or by the bitter xanthines caffeine,
      theobromine, and theophylline. We also tested the effects of bitter compounds on
      another essential element of the sweet taste transduction pathway, the type 3 IP3
      receptor (IP3R3). We found that IP3R3-mediated Ca(2+) flux is slightly enhanced
      by nicotine, not affected by saccharin, modestly inhibited by caffeine,
      theobromine, and theophylline, and strongly inhibited by quinine. Our results
      demonstrate that bitter compounds have differential effects on key elements of
      the sweet taste transduction pathway, suggesting for heterogeneous mechanisms of
      bitter-sweet taste interactions. 

PMID- 24452634
TI  - Utilization of FibroScan in clinical practice.
AB  - The evaluation of liver fibrosis is critical, particularly to rule out cirrhosis.
      Novel non-invasive tests such as transient ultrasound elastography are widely
      used to stage liver fibrosis as an alternative to liver biopsy, and this
      technology has recently been approved in the US. In this review, we discuss the
      performance characteristics of elastography for a variety of liver diseases and
      highlight practical appropriate suggestions for how to incorporate this
      technology into clinical practice. 

PMID- 24452635
TI  - Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines
      with epithelial to mesenchymal transition changes.
AB  - 5-Fluorouracil (5-FU) has been used for oral squamous cell carcinoma (OSCC)
      treatments, and the acquisition of resistance is the major problem to successful
      OSCC treatment. It has been reported that the epithelial to mesenchymal
      transition (EMT) is associated with chemoresistance in several types of cancers.
      In the present study, we established 5-FU-resistant OSCC cell lines (HSC2/FU and
      HSC4/FU), and aimed to elucidate the mechanism(s) involved in resistance in
      association with its EMT characteristics. MTT assay revealed that HSC2/FU is
      about 14-fold more resistant compared to HSC2, and HSC4/FU is 5-fold more
      resistant compared to HSC4. TUNEL assay also showed a dramatically decreased
      number of apoptotic cells in the 5-FU-resistant OSCC cell lines compared to each
      parental cell after treatment with 5-FU. Moreover, the 5-FU-resistant OSCC cell
      lines had typical morphologic phenotypes of EMT; loss of cell-cell adhesion,
      increased formation of pseudopodia and spindle-shaped morphology. Western blot
      analysis showed downregulated E-cadherin, and upregulated N-cadherin and Twist in
      the 5-FU-resistant OSCC cell lines. Results of our tumor xenograft studies
      coincide with our in vitro study data that confirmed the 5-FU resistant nature of
      HSC2/FU and HSC4/FU tumors. Moreover, immunohistochemistry showed that EMT
      changes (downregulated E-cadherin, and upregulated Twist and N-cadherin) occurred
      in the 5-FU-resistant xenografted tumor cells. These results suggest that EMT has
      important roles in the 5-FU-resistant OSCC cells, and that these resistant cells
      may be considered as useful tools for understanding the mechanisms involved in 5
      FU resistance in OSCC.

PMID- 24452636
TI  - RPRD1B promotes tumor growth by accelerating the cell cycle in endometrial
      cancer.
AB  - RPRD1B, the regulation of nuclear pre-mRNA domain containing 1B gene, functions
      as a cell cycle manipulator and has been found overexpressed in a small panel of
      endometrial cancer types. In the present study, we investigated the roles of
      RPRD1B in endometrial cancer using various in vitro and in vivo experiments.
      According to our results, RPRD1B mRNA was significantly upregulated in
      endometrial cancer tissues (P=0.0012). RPRD1B overexpression was correlated with
      tumor stage (P=0.0004), histology type (P=0.0146) and depth of myometrial
      invasion (P=0.024). In vitro, RPRD1B promoted cellular proliferation (P=0.032 for
      MTT assay and P=0.018 for colony formation assay), and accelerated the cell cycle
      (P=0.007) by upregulating cyclin D1, CDK4 and CDK6, while knockdown of RPRD1B
      suppressed cellular proliferation (P=0.02 for MTT assay and P=0.031 for colony
      formation assay), and led to G1 phase arrest (P=0.025) through downregulating
      cyclin D1, CDK4 and CDK6. Consistently, in the nude mice model, RPRD1B
      overexpression significantly accelerated the tumor xenograft growth (P=0.0012),
      accompanied by elevated Ki-67 and cyclin D1. In addition, we demonstrated that
      downregulating RPRD1B could sensitize Ishikawa cells to Raloxifene (P=0.01). In
      summary, we demonstrated that RPRD1B was frequently overexpressed in human
      endometrial cancer. Both in vitro and in vivo, over-abundant RPRD1B could promote
      tumor growth and accelerate cellular cell cycle. In addition, knockdown of RPRD1B
      also increased cell sensitivity to Raloxifene, making RPRD1B a potent therapeutic
      target for endometrial cancer, particularly in patients with resistance to the
      selective ER modulators.

PMID- 24452637
TI  - Field dissipation and plant uptake of benzotriazole ultraviolet stabilizers in
      biosolid-amended soils.
AB  - Benzotriazole ultraviolet stabilizers (BUVSs) have been commonly used in
      industrial and household product formulations, and have been detected in
      biosolids from wastewater treatment plants. However, little is known about their
      occurrence and dissipation behavior in the soil environment associated with
      biosolid application. This study investigated the occurrence and dissipation of
      five typical BUVSs (UV-326, UV-327, UV-328, UV-329 and UV-P) in biosolid-amended
      soils, and the uptake of these biocides by plants. The field trial includes two
      treatment groups: old groups with biosolid application at rates of 5, 10, 20 and
      40 t ha(-1) every year within 5 years, and new groups with only one biosolid
      application. The results showed that the five BUVSs could be detected in most
      biosolid-amended soils at a few to tens of ng g(-1) levels, but not detected in
      the control soils. These chemicals were not found in the crop plants collected
      from the trial plots. Moreover, high biosolid application rates and repeated
      biosolid applications resulted in high accumulation of these BUVSs in soil.
      During one year monitoring, the five BUVSs were significantly dissipated in the
      biosolid-amended soils with their half-lives ranging from 79 to 223 days, which
      were comparable with the modeling results. The results from this study
      demonstrated the persistence of BUVSs in soil environments with quite slow
      dissipation rates. 

PMID- 24452638
TI  - ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in
      the kidneys of db/db mice.
AB  - Epigenetics plays a key role in the pathogenesis of diabetic nephropathy (DN),
      although the precise regulatory mechanism is still unclear. Here, we examined the
      role of endoplasmic reticulum (ER) stress in histone H3 lysine 4 (H3K4)
      methyltransferase SET7/9-induced monocyte chemoattractant protein-1 (MCP-1)
      expression in the kidneys of db/db mice. Our results indicate that the expression
      of MCP-1 significantly increased in the kidneys of db/db mice in a time-dependent
      manner. An increased chromatin mark associated with an active gene (H3K4me1) at
      MCP-1 promoters accompanied this change in expression. The expression of SET7/9
      and the recruitment to these promoters were also elevated. SET7/9 gene silencing
      with small interfering (si) RNAs significantly attenuated the expression of
      H3K4me1 and MCP-1. Furthermore, expression of signaling regulator glucose
      regulated protein 78 (GRP78), a monitor of ER stress, significantly increased in
      the kidneys of db/db mice. The expression of spliced X-box binding protein 1
      (XBP1s), an ER stress-inducible transcription factor, and recruitment to the
      SET7/9 promoters were also increased. XBP1s gene silencing with siRNAs
      significantly attenuated the expression of SET7/9, H3K4me1, and MCP-1. The
      chaperone betaine not only effectively downregulated the GRP78 and XBP1s
      expression levels but also markedly decreased the SET7/9, H3K4me1, and MCP-1
      levels. Luciferase reporter assay demonstrated that XBP1s participated in ER
      stress-induced SET7/9 transcription, Taken together, these results reveal that ER
      stress can trigger the expression of MCP-1, in part through the XBP1s-mediated
      induction of SET7/9. 

PMID- 24452639
TI  - Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita
      mice.
AB  - Angiotensin-converting enzyme 2 (ACE2) is located in several tissues and is
      highly expressed in renal proximal tubules, where it degrades the vasoconstrictor
      angiotensin II (ANG II) to ANG-(1-7). Accumulating evidence supports protective
      roles of ACE2 in several disease states, including diabetic nephropathy. A
      disintegrin and metalloprotease (ADAM) 17 is involved in the shedding of several
      transmembrane proteins, including ACE2. Our previous studies showed increased
      renal ACE2, ADAM17 expression, and urinary ACE2 in type 2 diabetic mice
      (Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. PLoS One 8:
      e62833, 2013). The aim of the present study was to determine the effect of
      insulin on ACE2 shedding and ADAM17 in type 1 diabetic Akita mice. Results
      demonstrate increased renal ACE2 and ADAM17 expression and increased urinary ACE2
      fragments (~70 kDa) and albumin excretion in diabetic Akita mice. Immunostaining
      revealed colocalization of ACE2 with ADAM17 in renal tubules. Renal proximal
      tubular cells treated with ADAM17 inhibitor showed reduced ACE2 shedding into the
      media, confirming ADAM17-mediated shedding of ACE2. Treatment of Akita mice with
      insulin implants for 20 wk normalized hyperglycemia and decreased urinary ACE2
      and albumin excretion. Insulin also normalized renal ACE2 and ADAM17 but had no
      effect on tissue inhibitor of metalloproteinase 3 (TIMP3) protein expression.
      There was a positive linear correlation between urinary ACE2 and albuminuria,
      blood glucose, plasma creatinine, glucagon, and triglycerides. This is the first
      report showing an association between hyperglycemia, cardiovascular risk factors,
      and increased shedding of urinary ACE2 in diabetic Akita mice. Urinary ACE2 could
      be used as a biomarker for diabetic nephropathy and as an index of intrarenal
      ACE2 status. 

PMID- 24452641
TI  - Tonabersat for migraine prophylaxis: a systematic review.
AB  - BACKGROUND: Randomized clinical trials assessing the efficacy and tolerability of
      tonabersat compared with placebo as prophylaxis for migraine were systematically
      reviewed in this study. By analyzing all available data, we aimed to establish an
      overall estimate of any association in order to more accurately inform clinicians
      and care-givers about how to prevent migraines. OBJECTIVE: To evaluate the
      efficacy and tolerability of tonabersat when it is used for migraine prevention.
      STUDY DESIGN: Systematic review of tonabersat for migraine prophylaxis. METHODS:
      Computerized database search of The Cochrane Pain, Palliative & Supportive Care
      Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library), Pubmed, and EMBASE for randomized, double-blind, placebo
      controlled trials on tonabersat for migraine until January, 2013. We also
      searched the ongoing trials. We did not impose any language restrictions.The
      quality assessment and clinical relevance criteria utilized were the Cochrane
      Pain, Palliative & Supportive Care review group criteria as utilized for
      randomized trials. OUTCOME MEASURES: The primary outcome measure was the change
      in mean number of migraine headache days. The secondary outcome measures were
      change in attacks, responder rates, the reduction of the consumption of rescue
      medication, and adverse events. RESULTS: For this systematic review, 133 studies
      were identified. Of these, 131 studies were excluded, and a total of 2 studies
      (after removal of duplicate publications) met inclusion criteria for
      methodological quality assessment with the randomized trial study. The evidence
      for tonabersat for migration prophylaxis failed to demonstrate a reduction when
      compared to placebo because of a lack of evidence. But the good tolerability
      supports further exploration of tonabersat in the prevention of migraine attacks.
      LIMITATIONS: The limitation of this systematic review was a lack of available
      evidence. CONCLUSION: There is fair evidence for migraine prophylaxis, but a lack
      of available evidence for tonabersat for migraine prophylaxis. Although
      tonabersat failed to demonstrate a significantly greater reduction of migraine
      headache days than placebo, it was well tolerated. Future work should further
      investigate the utility of tonabersat in the preventive management of migraine.

PMID- 24452642
TI  - Intravascular flow detection during transforaminal epidural injections: a
      prospective assessment.
AB  - BACKGROUND: Transforaminal epidural steroid injections (TFESI) are a mainstay in
      the treatment of spine pain. Though this commonly performed procedure is
      generally felt to be safe, devastating complications following inadvertent intra
      arterial injections of particulate steroid have been reported. The use of digital
      subtraction angiography (DSA) has been suggested as a means of detecting intra
      arterial needle placements prior to medication injection. OBJECTIVE: To examine
      the efficacy of DSA in detecting intra-arterial needle placements during TFESI.
      STUDY DESIGN: Prospective cohort study evaluating the impact of DSA on detecting
      intra-arterial needle placements during TFESI. METHODS: We enrolled 150
      consecutive patients presenting to a university-affiliated spine center with
      discogenic and/or radicular symptoms affecting the cervical, lumbar, and sacral
      regions. For each injection, prior to imaging with DSA, traditional methods for
      vascular penetration detection were employed, including the identification of
      blood in the needle hub (flash), negative aspiration of blood prior to injection,
      and live fluoroscopic injection of contrast. Once these tests were performed and
      negative for signs of intra-arterial needle placement, DSA imaging was utilized
      prior to medication administration for identification of vascular flow. RESULTS:
      A total number of 222 TFESI were performed, 41 injections at the cervical levels
      (18.47%), 113 at the lumbar levels (50.9%), and 68 at the sacral levels (30.36%).
      Flash was observed in 13 injections performed (5.85% of the total number of
      injections): one (0.45%) in the cervical, 2 (0.9%) in the lumbar, and 10 (4.5%)
      in the sacral levels. In 11 TFESI blood aspiration was obtained (4.95% of all
      injections): 3 (1.3%) in cervical, 4 (1.8%) in lumbar, and 4 (1.8%) in sacral
      injections. Live fluoroscopy during contrast injection detected 46 (20.72%)
      intravascular flow patterns: 7 (3.1%) cervical, 17 (7.6%) lumbar, and 22 (9.9%)
      sacral. DSA identified an additional 5 intravascular injections after all
      previous steps had resulted in negative vascular penetration signs, which
      accounted for 2.25% of all injections. LIMITATIONS: This is a prospective, single
      center study with a relatively small number of patients and no control group.
      CONCLUSION: DSA detected additional 5.26% intravascular needle placements
      following traditional methods. Our findings also support other studies that
      conclude TFESI are generally a safe procedure. We recommend that special
      attention should be paid to the sacral injections as vascular penetration was
      statistically higher than at other levels.

PMID- 24452640
TI  - Measurement of renal tissue oxygenation with blood oxygen level-dependent MRI and
      oxygen transit modeling.
AB  - Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of
      tissue oxygenation level (Po2), is in fact influenced by multiple confounding
      factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to
      explore the feasibility of extracting tissue Po2 from renal BOLD data. A method
      of two steps was proposed: first, a Monte Carlo simulation to estimate blood
      oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to
      convert SHb to tissue Po2. The proposed method was calibrated and validated with
      20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue
      Po2 was compared with microprobe-measured values. The method was then applied to
      nine healthy human subjects (age: 25.7 +/- 3.0 yr) in whom BOLD was performed
      before and after furosemide. For the 12 pigs before furosemide injection, the
      proposed model estimated renal tissue Po2 with errors of 2.3 +/- 5.2 mmHg (5.8 +/
      13.4%) in cortex and -0.1 +/- 4.5 mmHg (1.7 +/- 18.1%) in medulla, compared with
      microprobe measurements. After injection of furosemide, the estimation errors
      were 6.9 +/- 3.9 mmHg (14.2 +/- 8.4%) for cortex and 2.6 +/- 4.0 mmHg (7.7 +/-
      11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased
      from 16.0 +/- 4.9 mmHg (SHb: 31 +/- 11%) at baseline to 26.2 +/- 3.1 mmHg (SHb:
      53 +/- 6%) at 5 min after furosemide injection, while cortical Po2 did not change
      significantly at ~58 mmHg (SHb: 92 +/- 1%). Our proposed method, validated with a
      porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI
      data in human subjects. 

PMID- 24452643
TI  - Occipital nerve stimulation in the treatment of medically intractable SUNCT and
      SUNA.
AB  - BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with
      conjunctival injection and tearing (SUNCT) or with cranial autonomic symptoms
      (SUNA) are primary headaches characterized by frequent attacks of severe
      headaches in association with cranial autonomic features. Patients with chronic
      SUNCT or SUNA have unremitting symptoms that necessitate prolonged use of medical
      preventive treatments, many of which are prone to causing side effects. They can
      be medically intractable, in which case neurally destructive or cranially
      invasive surgical treatments can be offered, though these have hitherto yielded
      conflicting results. Occipital nerve stimulation (ONS) offers a nondestructive
      and relatively low risk surgical alternative. OBJECTIVE: To assess the efficacy
      and safety of ONS in chronic, medically intractable SUNCT and SUNA patients.
      STUDY DESIGN: Prospective open-label study. METHODS: Nine medically intractable,
      chronic SUNCT and SUNA patients were implanted with electrodes for bilateral
      occipital nerve stimulation. Data were collected prospectively for pre- and
      postimplantation headache characteristics, including frequency, intensity and
      duration of attacks. Diaries were used to assess headache improvement. RESULTS:
      At a median follow-up of 38 months (range 24-55 months), all but one patient
      reported substantial improvement. Four patients became pain-free, 3 were almost
      pain-free (96 - 98% improvement), and one had a marked reduction in attack
      frequency and severity (81% improvement). After an initial rapid improvement, the
      maximum benefit of ONS was attained after a lag of a few months. Device
      malfunction was followed by recurrence or worsening of the attacks within a few
      days in most patients. Adverse events included lead migration, exposure of the
      electrode, and pain due to muscle recruitment over the leads. One patient
      developed hemicrania continua one month after implantation and was successfully
      treated with indomethacin. CONCLUSION: ONS appears to offer an effective and safe
      treatment option, without significant morbidity, for medically intractable SUNCT
      and SUNA. Given the variable results with cranially invasive or neurally
      destructive surgery, ONS might be considered the surgical treatment of choice for
      medically intractable SUNCT and SUNA.

PMID- 24452644
TI  - Pelvic belt effects on sacroiliac joint ligaments: a computational approach to
      understand therapeutic effects of pelvic belts.
AB  - BACKGROUND: The sacroiliac joint is a widely described source of low back pain.
      Therapeutic approaches to relieve pain include the application of pelvic belts.
      However, the effects of pelvic belts on sacroiliac joint ligaments as potential
      pain generators are mostly unknown. OBJECTIVES: The aim of our study was to
      analyze the influence of pelvic belts on ligament load by means of a computer
      model. STUDY DESIGN: Experimental computer study using a finite element method.
      METHODS: A computer model of the human pelvis was created, comprising bones,
      ligaments, and cartilage. Detailed geometries, material properties of ligaments,
      and in-vivo pressure distribution patterns of a pelvic belt were implemented. The
      effects of pelvic belts on ligament strain were computed in the double-leg
      stance. RESULTS: Pelvic belts increase sacroiliac joint motion around the
      sagittal axis but decrease motion around the transverse axis. With pelvic belt
      application, most of the strained sacroiliac joint ligaments were relieved,
      especially the sacrospinous, sacrotuberous, and the interosseous sacroiliac
      ligaments. Sacroiliac joint motion and ligament strains were minute. These
      results agree with validation data from other studies. LIMITATIONS: Assigning
      homogenous and linear material properties and excluding muscle forces are clear
      simplifications of the complex reality. CONCLUSIONS: Pelvic belts alter
      sacroiliac joint motion and provide partial relief of ligament strain that is
      subjectively marked, although minimal in absolute terms. These findings confirm
      theories that besides being mechanical stabilizers, the sacroiliac joint
      ligaments are likely involved in neuromuscular feedback mechanisms. The results
      from our computer model help with unraveling the therapeutic mechanisms of pelvic
      belts.

PMID- 24452645
TI  - Is Life better after motor cortex stimulation for pain control? Results at long
      term and their prediction by preoperative rTMS.
AB  - BACKGROUND: A positive effect of motor cortex stimulation (MCS) (defined as
      subjective estimations of pain relief >= 30%) has been reported in 55 - 64% of
      patients. Repetitive magnetic cortical stimulation (rTMS) is considered a
      predictor of MCS effect. These figures are, however, mostly based on subjective
      reports of pain intensity, and have not been confirmed in the long-term.
      OBJECTIVES: This study assessed long-term pain relief (2 - 9 years) after
      epidural motor cortex stimulation and its pre-operative prediction by rTMS, using
      both intensity and Quality of Life (QoL) scales. STUDY DESIGN: Analysis of the
      long-term evolution of pain patients treated by epidural motor cortex
      stimulation, and predictive value of preoperative response to rTMS. SETTING:
      University Neurological Hospital Pain Center. METHODS:  PATIENTS: Twenty patients
      suffering chronic pharmaco-resistant neuropathic pain. INTERVENTION: All patients
      received first randomized sham vs. active 20 Hz-rTMS, before being submitted to
      MCS surgery. MEASUREMENT: Postoperative pain relief was evaluated at 6 months and
      then up to 9 years post-MCS (average 6.1 +/- 2.6 y) using (i) pain numerical
      rating scores (NRS); (ii) a combined assessment (CPA) including NRS, drug intake,
      and subjective quality of life; and (iii) a short questionnaire (HowRu) exploring
      discomfort, distress, disability, and dependence. RESULTS: Pain scores were
      significantly reduced by active (but not sham) rTMS and by subsequent MCS. Ten
      out of 20 patients kept a long-term benefit from MCS, both on raw pain scores and
      on CPA. The CPA results were strictly comparable when obtained by the surgeon or
      by a third-party on telephonic survey (r = 0.9). CPA scores following rTMS and
      long-term MCS were significantly associated (Fisher P = 0.02), with 90% positive
      predictive value and 67% negative predictive value of preoperative rTMS over long
      term MCS results. On the HowRu questionnaire, long-term MCS-related improvement
      concerned "discomfort" (physical pain) and "dependence" (autonomy for daily
      activities), whereas "disability" (work, home, and leisure activities) and
      "distress" (anxiety, stress, depression) did not significantly improve.
      LIMITATIONS: Limited cohort of patients with inhomogeneous pain etiology.
      Subjectivity of the reported items by the patient after a variable and long delay
      after surgery. Predictive evaluation based on a single rTMS session compared to
      chronic MCS. CONCLUSIONS: Half of the patients still retain a significant benefit
      after 2 - 9 years of continuous MCS, and this can be reasonably predicted by
      preoperative rTMS. Adding drug intake and QoL estimates to raw pain scores allows
      a more realistic assessment of long-term benefits and enhance the rTMS predictive
      value. The aims of this study and its design were approved by the local ethics
      committee (University Hospitals St Etienne and Lyon, France).

PMID- 24452646
TI  - Utility of oral fluid in compliance monitoring of opioid medications.
AB  - BACKGROUND: Prescription drug abuse is the fastest growing drug problem in the
      United States, and the increase in unintentional drug overdose deaths has been
      driven by the increase in opioid analgesic use. Given the epidemic of non-medical
      prescription pain reliever use and the current medico-legal climate, it is
      increasingly important for the prescriber to monitor for medication compliance.
      OBJECTIVES: The purpose of this IRB approved study is to compare the results of
      oral fluid (OF) and routine urinalysis for monitoring compliance in a single
      academic pain management program in an urban setting in order to evaluate the
      utility of OF analysis in compliance monitoring when prescribing opioid
      medications. STUDY DESIGN: Outcomes analysis of prospective, consecutive, paired
      comparison study with clinical implications. SETTING: Single academic
      interventional pain management center in the United States. METHODS: Paired OF
      and urine specimens were collected for each patient with signed informed consent,
      at the Institute for Pain Medicine, Western Pennsylvania Hospital, from patients
      who routinely donated urine on a random basis for compliance testing. A total of
      153 paired specimens were analyzed. Demographic and prescription data were made
      available. Specimens were screened using immunoassay and presumptive positive
      findings were confirmed with liquid-chromatography and mass spectrometry.
      Although both matrices were tested for a wider range of medications, the data
      presented here are representative of analgesic opioids and benzodiazepine drug
      classes only. RESULTS: Following exclusion criteria, of the 132 remaining
      specimen pairs that were positive for opioids or benzodiazepines in at least one
      matrix, 101 pairs showed exact drug class matches (76.5%). In an additional 21
      pairs, at least one drug class was positive in both matrices (15.9%), giving an
      overall agreement of 92.4%. Overall, 191 positive results were found in urine
      averaging 1.4 drugs per specimen; 176 positives were detected using OF for an
      average of 1.3 drugs per specimen. CONCLUSIONS: In the setting of stable dosing
      of prescription opioids and/or concomitant illicit drug use, given comparable
      detection rates between urine and OF matrix qualitative results, the OF matrix
      for drug testing for compliance monitoring may serve as a useful and valid
      testing tool. The authors conclude that overall OF analysis produces comparable
      results to urine sample analysis with detection rates differing primarily due to
      differences in windows of detection for different drug classes. LIMITATIONS: The
      limitations include the study was performed in a single academic center in an
      urban community. Also, there is a paucity of literature regarding windows of
      detection for OF analysis compared to urine. IRB: APPROVED - Allegheny-Singer
      Research Institute West Penn Allegheny Heath System (ASRI-WPAHS) - IRB Study
      #FWA00015120.

PMID- 24452647
TI  - Thermal pain in complex regional pain syndrome type I.
AB  - BACKGROUND: Quantitative sensory testing (QST), with thermal threshold
      determinations, is a routine part of the comprehensive clinical workup of
      patients suffering from chronic pain, especially those with Complex Regional Pain
      Syndrome seen at our outpatient pain clinic. This is done to quantitatively
      assess each patient's small fiber and sensory function in a controlled manner.
      Most patients have normal sensory detection thresholds, but there are large
      differences in thermal pain thresholds. Some patients display no thermal
      hyperalgesia, while other patients display severe thermal hyperalgesia when
      tested in all 4 limbs. OBJECTIVES: To ascertain the prevalence of thermal
      hyperalgesia in patients with complex regional pain syndrome type 1 (CRPS-I).
      STUDY DESIGN: This was a retrospective review of the results of QST performed on
      105 patients as part of their clinical workup. SETTING: The outpatient clinic of
      the Department of Neurology at Drexel University College of Medicine. METHODS:
      All patients had a diagnosis of CRPS-I. Thermal quantitative sensory testing,
      including cool detection, warm detection, cold pain, and heat pain, was performed
      on 8 distal sites on each patient as part of a comprehensive clinical
      examination. RESULTS: With regards to thermal hyperalgesia, patients with CPRS-I
      appear to fall into distinct groups. One subgroup displays evidence of
      generalized cold and heat hyperalgesia, one subgroup displays evidence of
      generalized cold hyperalgesia only, one displays evidence of heat hyperalgesia
      only, and one subgroup does not display evidence of cold or heat hyperalgesia.
      LIMITATIONS: This study is based on retrospective information on a relatively
      small (105 patient records) number of patients. Since only patients with CRPS-I
      were included, the results are only applicable to this group. CONCLUSIONS:
      Thermal QST provides useful information about the sensory phenotype of individual
      patients. Subgrouping based on thermal hyperalgesia may be useful for future
      studies regarding prognosis, treatment selection, and efficacy.

PMID- 24452648
TI  - Medication compliance in patients with chronic pain.
AB  - BACKGROUND: Despite hints about the high incidence of pain patients misreporting
      their pain medication use, there are only a few non-controlled studies on the
      topic that focus solely on opioids. OBJECTIVE: Using toxicological analyses in a
      cross-sectional study, we investigated patients' reliability regarding their
      report of any current pain medication use. STUDY DESIGN: A cross-sectional study.
      SETTING: A comprehensive pain center and a surgical unit of a German University
      Hospital. METHODS: Consecutive outpatients at their first visit to the pain
      clinic (PG, n = 243) and pre-surgical control patients (SG, n = 100) suffering
      from pain reported on their current pain medication. The patients' reports were
      verified in serum and urine using specific toxicological methods. Two types of
      noncompliance were defined: under-reporting (detection of non-reported
      substances) and over-reporting (reported substances undetectable). The impact of
      clinical parameters on compliance was investigated using binary logistic
      regression. RESULTS: The incidence of noncompliance was significantly higher in
      the PG (43.3%) than in the SG (24%; P < 0.05). Under-reporting occurred similarly
      in both groups (31% PG; 23% SG), whereas over-reporting predominantly appeared in
      the PG (11% vs. 2%; P < 0.05). Opioids were not most frequently under-reported,
      but the highest proportion of under-reported drugs (under-reported in relation to
      detection incidence) was found for non-opioid analgesics (NSAIDs: 29% PG; 25% SG;
      other: 42% PG; 32% SG) and psychotropic drugs (35% PG; 53% SG). In the PG,
      logistic regression revealed high depression scores to be predictive for
      noncompliance (odds ratio 2.12). LIMITATIONS: Due to lack of a structured follow
      up interview motives of under- and over-reporting stay speculative. CONCLUSIONS:
      Under-reporting of non-opioid analgesics is the main type of noncompliance, a
      disquieting fact in light of their toxicity and adverse effects. Further research
      is required in terms of drug assessment and compliance improvement strategies in
      pain clinics; therefore, toxicological monitoring is indispensable. CLINICAL
      TRIAL: NCT01625065; Medi-3889-10.

PMID- 24452649
TI  - Evidence of specific cognitive deficits in patients with chronic low back pain
      under long-term substitution treatment of opioids.
AB  - BACKGROUND: There is a growing number of patients worldwide being treated with
      long-term opioids for chronic non-cancer pain, although there is limited evidence
      for their effectiveness in improving pain and function. Opioid-use related
      adverse effects, especially in cognitive functioning in these patients, are
      rarely evaluated. OBJECTIVES: The present study investigated the cognitive
      functions of patients with chronic back pain who underwent long-term opioid
      treatment in comparison with those patients without opioid usage and healthy
      controls. STUDY DESIGN: A prospective, nonrandomized, cross-sectional study.
      SETTING: Multidisciplinary pain management clinic, specialty referral center,
      University Hospital in Germany. METHODS: In a prospective cross-sectional design,
      37 patients with chronic back pain who underwent long-term opioid therapy (OP)
      were compared with 33 patients with chronic back pain without opioid therapy (NO)
      and 25 healthy controls (HC). Assessment of primary outcome included cognitive
      function such as information processing speed, choice reaction time, pattern
      recognition memory, and executive function. Other data included pain, back
      function, depression and anxiety, use of medication, and education status. The
      relationship between cognitive functions and anxiety/depression was analysed.
      RESULTS: Both patient groups needed significantly longer time in information
      processing when compared to HC (Group 1: 41.87 +/- 20.47 Group 2: 38.29 +/- 19.99
      Group 3: 30.25 +/- 14.19). Additionally, OP patients had significantly reduced
      spatial memory capacity, flexibility for concept change, and impaired performance
      in working memory assessment compared to NO patients and HC. The impaired
      cognitive outcomes were significantly associated with pain intensity, depression
      scores, and medication use. LIMITATIONS: Limitations include small number of
      patients with heterogeneous opioid therapy and the nonrandomized observational
      nature of the study. CONCLUSIONS: Our findings give a differential view into the
      cognitive changes from chronic back pain with and without long-term opioids
      treatment. Chronic back pain itself impairs some distinct cognitive functions.
      Long-term opioid therapy adds further cognitive impairment.

PMID- 24452651
TI  - Opioids in chronic noncancer pain: have we reached a boiling point yet?

PMID- 24452650
TI  - Craniofacial pain and disability inventory (CF-PDI): development and psychometric
      validation of a new questionnaire.
AB  - BACKGROUND: Orofacial pain, headaches, and neck pain are very common pain
      conditions in the general population and might be associated in their
      pathophysiology, although this is not yet clarified. The development and
      validation of a prediction inventory is important to minimize risks. Most recent
      questionnaires have not focused on pain, but pain is the common symptom in
      temporomandibular disorders, headaches, and neck pain. It is necessary to provide
      tools for these conditions. OBJECTIVES: The purpose of this study is to present
      the development and analysis of the factorial structure and psychometric
      properties of a new self-administered questionnaire (Craniofacial Pain and
      Disability Inventory [CF-PDI]) designed to measure pain, disability, and
      functional status of the mandibular and craniofacial regions. STUDY DESIGN:
      Multicenter, prospective, cross-sectional, descriptive survey design. A secondary
      analysis of the reliability of the measures was a longitudinal, observational
      study. SETTING: A convenience sample was recruited from a hospital and 2
      specialty clinics in Madrid, Spain. METHODS: The study sample consisted of 192
      heterogeneous chronic craniofacial pain patients. A sub-sample of 106 patients
      was asked to answer the questionnaire a second time, to assess the test-retest
      reliability. The development and validation of the CF-PDI were conducted using
      the standard methodology, which included item development, cognitive debriefing,
      and psychometric validation. The questionnaire was assessed for the following
      psychometric properties: internal consistency (Cronbach's alpha); floor and
      ceiling effects; test-retest reliability (Intraclass Correlation Coefficient
      [ICC]; Bland and Altman method); construct validity (exploratory factor
      analysis); responsiveness (standard error of measurement [SEM] and minimal
      detectable change [MDC]); and convergent validity (Pearson correlation
      coefficient), by comparing visual analog scale (VAS), the Tampa Scale for
      Kinesiophobia (TSK-11), the Pain Catastrophizing Scale (PCS), the Neck Disability
      Index (NDI), and the Headache Impact Test-6 (HIT-6). Multiple linear regression
      analysis was used to estimate the strength of the associations with theoretically
      similar constructs. RESULTS: The final version of the CF-PDI consists of 21
      items. Exploratory factor analysis revealed 2 factors ("pain and disability" and
      "jaw functional status"), both with an eigenvalue greater than one, explaining
      44.77% of the variance. Floor or ceiling effects were not observed. High internal
      consistency of the CF-PDI (Cronbach's alpha: 0.88) and also of the 2 subscales
      (Cronbach's alpha: 0.80 - 0.86) was confirmed. ICC was found to be 0.90 (95%
      confidence interval [CI] 0.86 - 0.93), which was considered to be excellent test
      retest reliability. The SEM and MDC were 2.4 and 7 points, respectively. The
      total CF-PDI score showed a moderate correlation with most of the assessed
      questionnaires (r = 0.36 - 0.52) and a strong correlation with the NDI (r = 0.65;
      P < 0.001). The NDI, VAS, and TSK-11 were predictors of CF-PDI. LIMITATIONS: Only
      self-reported measures were considered for convergent validity. Future research
      should use physical tests to explore the clinical signs relating to pain and
      disability. CONCLUSION: The CF-PDI showed good psychometric properties. Based on
      the findings of this study, the CF-PDI can be used in research and clinical
      practice for the assessment of patients with craniofacial pain.

PMID- 24452652
TI  - Ganglion Impar block for sympathetically mediated pain in a patient with a
      rectourethral fistula.

PMID- 24452653
TI  - Ankle brachial index and exercise transcutaneous oxygen pressure measurement in
      patients with peripheral artery disease and lumbar spinal stenosis.

PMID- 24452654
TI  - Declining value of work of interventional pain physicians.

PMID- 24452655
TI  - The tragedy of the sustained growth rate formula continues into 2014: is there
      hope for repeal?

PMID- 24452656
TI  - Anti-tumor necrosis factor antagonists in the treatment of low back pain and
      radiculopathy: a systematic review and meta-analysis.
AB  - BACKGROUND: Low back pain, with or without radiculopathy, is an important cause
      of disability and economic expenditure. However, many patients are not achieving
      optimal pain control with existing medications. Tumor necrosis factor antagonists
      (anti-TNFalpha) could be an alternative drug treatment. OBJECTIVES: Systematic
      review the efficacy and safety of anti-TNFalpha in the treatment of low back pain
      with or without radiculopathy. STUDY DESIGN: Inclusion criteria were
      observational studies with safety as an outcome, and randomized or nonrandomized
      controlled trial (RCT) studies on efficacy and/or safety of anti-TNFalpha drugs
      on low back pain. Exclusion criteria included patients with auto-immune
      conditions or osteoporosis. RESULTS: Studies were assessed independently by 2
      authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance,
      quality, and strength of evidence (GRADE approach). Of the 1,179 studies
      retrieved, all duplicates were excluded and then the inclusion/exclusion criteria
      was applied. One observational study (n = 143) and 11 RCTs remained (n = 539): 8
      for etanercept (n = 304), one for adalimumab (n = 61), one for adalimumab and
      etanercept (n = 60), one for infliximab (n = 40) and one for REN-1654 (n = 74).
      Only 3 etanercept and 2 adalimumab studies showed statistically significant pain
      relief when compared to placebo. There was no difference in the overall incidence
      of adverse effects when comparing anti-TNF-alpha and placebo. LIMITATIONS:
      Despite the statistically significant effect, this meta-analysis has important
      limitations, such as high heterogeneity and high use of outcome imputation.
      CONCLUSIONS: There is low evidence that epidural etanercept has a low-to-moderate
      effect size when compared to placebo for pain due to discogenic lumbar
      radiculopathy (5 studies, n=185), with a standardized mean difference = -0.43
      (95% confidence interval [CI] -0.84 to -0.02).There is moderate evidence that
      epidural etanercept does not have a higher adverse effects incidence rate when
      compared to placebo for discogenic lumbar radiculopathy (5 studies, n = 185) with
      a relative risk (RR) = 0.84 (95% CI 0.53 to 1.34).There is moderate evidence that
      anti-TNFalpha does not have a higher adverse effects incidence rate when compared
      to placebo for low back pain (10 studies, n= 343) with an RR = 0.93 (95% CI 0.56
      to 1.55).We strongly suggest that anti-TNFalpha continue to be studied in
      experimental settings for the treatment of low back pain. We cannot currently
      recommend this therapy in clinical practice. New research could shed some light
      on the efficacy of anti-TNFalpha and change this recommendation in the future.

PMID- 24452657
TI  - Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a
      systematic review and a meta-analysis.
AB  - BACKGROUND: Low back pain with or without radiculopathy is an important cause of
      disability and economic expenditure. However, many patients are not meeting
      optimal pain control through existing treatments. Recent studies have linked
      nerve growth factor (NGF) and the pathophysiology of persistent pain. Anti-NGF
      could be an alternative drug treatment for low back pain. OBJECTIVE:
      Systematically review the efficacy and safety of anti-NGF in the treatment of low
      back pain. METHODS: A systematic review of the literature with no language, date
      or publication status restriction, using Medline, EMBASE, Cochrane Library, and
      the clinicaltrials.gov database. Additional literature was retrieved by
      conferring with experts in the field or reviewing bibliographies and annals of
      meetings and congresses. Search terms included "monoclonal antibodies," "nerve
      growth factor," "anti-ngf," "fulranumab," "tanezumab," "sciatica," "back pain,"
      and "spine." STUDY DESIGN: Inclusion criteria were observational studies with
      safety as an outcome and randomized or nonrandomized controlled trials studying
      the efficacy and/or the safety of anti-NGF drugs on low back pain. Exclusion
      criteria included patients with autoimmune conditions or osteoporosis. Studies
      were assessed independently by 2 authors regarding inclusion/exclusion criteria,
      risk of bias, clinical relevance, and quality of evidence (GRADE approach).
      RESULTS: 1,168 studies were retrieved. After excluding duplicates and applying
      the inclusion/exclusion criteria, 4 RCTs remained (n = 2,109): 2 for tanezumab,
      one for REGN475, and one for fulranumab. Only the tanezumab studies showed any
      significant difference over placebo (n = 1,563) for both pain relief and
      functional improvement. CONCLUSIONS: There is very low evidence that systemically
      administered anti-NGF therapy has a small positive effect compared to placebo for
      both pain relief (standarized mean difference [SMD] = -0.29, 95% confidence
      interval [CI] -0.58 to 0.00) and functional improvement (SMD = -0.21, 95%CI -0.37
      to -0.05 ) of low back pain. There was low evidence of adverse effects (AEs)
      compared to placebo and low evidence of neurological AEs than placebo (relative
      risk = 1.93, 95%CI 1.41 to 2.64).Tanezumab, as a specific anti-NGF treatment,
      showed low evidence of a small to moderate effect for pain relief of low back
      pain (SMD = -0.44, 95%CI -0.81 to -0.07); and low evidence of a small effect for
      functional improvement (SMD = -0.26, 95%CI -0.40 to -0.12) with systemic
      administration, although not clinically significant. Tanezumab and anti-NGFs
      overall had, respectively, moderate and low evidence of overall AEs and serious
      AEs and a higher risk of developing neurological AEs when compared with placebo.
      Although anti-NGF, specifically tanezumab, showed a low-to-moderate effect on
      pain relief and functional improvement, it cannot be recommended for low back
      pain treatment. Without more research on the pathophysiology of anti-NGFs and
      adverse effects, its use is not safe in the overall population. However, as
      corroborated by the US Food and Drug Administration, this meta-analysis
      underscores a role for greater insight into anti-NGF therapy for painful
      conditions that are refractory to current drugs, such as oncologic pain, chronic
      pancreatitis, and phantom-limb pain. Given the pathophysiology of axial pain
      involving inflammatory mediators and the adverse effects of systemic anti-NGF
      use, consideration of local therapies may warrant further exploration.

PMID- 24452658
TI  - A randomized, double-blind, active-control trial of the effectiveness of lumbar
      interlaminar epidural injections in disc herniation.
AB  - BACKGROUND: Among the multiple nonsurgical modalities, epidural injections are
      one of the most commonly utilized treatment modalities in managing chronic low
      back and lower extremity pain due to disc herniation and radiculitis. There is a
      paucity of randomized trials from contemporary interventional pain management
      settings utilizing fluoroscopy with long-term follow-up. STUDY DESIGN:
      Randomized, double-blind, active-controlled trial with 2-year follow-up. SETTING:
      An interventional pain management practice in the United States. OBJECTIVE: The
      objective was to assess the effectiveness of lumbar interlaminar epidural
      injections of local anesthetic with or without steroids for managing chronic low
      back pain of disc herniation or radiculitis. METHODS: Two groups of patients were
      studied, with 60 patients in each group receiving either local anesthetic only or
      local anesthetic mixed with betamethasone. OUTCOME MEASURES: The primary outcome
      measure was defined as pain relief and functional status improvement of 50%. The
      outcomes were assessed by numeric rating scale (NRS) of pain and functional
      status with Oswestry Disability Index (ODI). Secondary outcome measures included
      employment status and opioid intake. RESULTS: Results showed significant
      improvement in 60% of patients in Group I and 70% of patients in Group II at the
      end of 2 years. In addition, in the successful groups, those with at least 3
      weeks of relief (with the first 2 procedures), the improvement was 72% in Group I
      and 71% in Group II. Results were somewhat superior for pain relief at 6 months
      and functional status at 12 months in the steroid group. Thus, the results
      indicate that a patient's failure to respond to local anesthetic alone, may be
      treated with addition of steroids. LIMITATIONS: The results of the study are
      limited by the lack of a placebo group. CONCLUSION: Lumbar interlaminar epidural
      injections of local anesthetic with or without steroids is an effective modality,
      in patients with chronic function limiting low back and lower extremity pain
      secondary to disc herniation after failure of conservative modalities.

PMID- 24452659
TI  - Adjuvant hyaluronidase to epidural steroid improves the quality of analgesia in
      failed back surgery syndrome: a prospective randomized clinical trial.
AB  - BACKGROUND: Management of low back pain after spinal surgeries is one of the most
      challenging problems in pain medicine. Transforaminal lumbar epidural steroid
      injection has been used with inconsistent response. Most patients require
      multiple and frequent injections due to high recurrence of back pain. OBJECTIVE:
      To find out whether the addition of hyaluronidase to the epidural injectate
      affects the quality and duration of analgesia in patients with low back pain
      secondary to failed back surgery syndrome. STUDY DESIGN: Prospective randomized
      trial. METHODS: The study was registered in the Government Clinical Trial
      registry and the protocol was reviewed and approved by the institutional review
      board. After obtaining an informed consent, 25 patients with low back pain due to
      failed back syndrome were randomly assigned to receive a transforaminal epidural
      injection of hyaluronidase 1500 IU (HYL) or normal saline (NSL) to a mixture of
      bupivacaine 0.5% (1 mL) and triamcinolone 40 mg (1 mL) in a double-blind fashion.
      An interventional pain specialist using fluoroscopic guidance performed all
      epidural injections. The patients received a comprehensive neurological
      examination by a non-interventional pain specialist who was blinded to the
      treatment during their follow-up visits, scheduled one, 2, and 4 weeks after the
      intervention. Numerical pain scores, analgesic requirement, and satisfaction
      scores were recorded during every visit. RESULTS: There was no difference in
      demographic data between the 2 groups. Pain scores and total analgesic
      requirement were significantly lower in the HYL group at 2 and 4 weeks after
      blockade (P < 0.01). Patient satisfaction was higher in the HYL group.
      LIMITATIONS: The study was limited by a relatively small sample size. CONCLUSION:
      We conclude that adding hyaluronidase to the epidural injectate was effective in
      the management of chronic low back pain in patients with failed back surgery
      syndrome demonstrated over a period of 4 weeks.

PMID- 24452660
TI  - Combined ultrasound and fluoroscopic guidance for radiofrequency ablation of the
      obturator nerve for intractable cancer-associated hip pain.
AB  - Management of pain from skeletal metastases is notoriously difficult. Case
      reports and case series have described radiofrequency ablation of the obturator
      nerve branches to the femoral head for treatment of intractable hip pain.
      Ablation of the obturator branches to the femoral head is technically difficult
      because of bony and vascular anatomy, including close proximity of the femoral
      vessels. Here we present the case of a 79-year-old woman with intractable right
      hip pain and inability to ambulate secondary to metastatic non-small cell lung
      cancer in the femoral head and acetabulum, treated with thermal radiofrequency
      ablation of the obturator and femoral nerve branches to the femoral head.
      Ablation of the obturator nerve was done via anterior placement of the
      radiofrequency needle under combined ultrasound and fluoroscopic guidance,
      passing the radiofrequency needle between the femoral artery and femoral vein.
      Real-time ultrasound guidance was used to avoid vascular puncture. Thermal
      radiofrequency ablation resulted in sustained pain relief, and resumption in the
      ability of the patient to ambulate. From this case we suggest that an anterior
      approach to the obturator nerve branches to the femoral head may be technically
      feasible using combined ultrasound and fluoroscopic guidance to avoid vascular
      puncture. 

PMID- 24452661
TI  - Radioisotope cisternography: a potentially useful tool for headache diagnosis in
      patients with an IDD pump.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) and related headache after
      intrathecal pump implantation is a possibility. Knowing the exact location of the
      cerebrospinal fluid (CSF) leak is mandatory for managing with interventional
      therapies. OBJECTIVES: Radioisotope cisternography (RICG) is a common procedure
      in nuclear medicine and may be used as an additional procedure in the
      differential diagnosis of headaches due to intracranial liquor hypotension
      syndrome caused by microleakage of CSF. STUDY DESIGN: We report an imaging case
      of complex chronic headache in a patient with an implanted drug delivery pump.
      The symptomatology of the patient was considered typical of spontaneous
      intracranial hypotension (SIH). Therefore, the initial suspicion was the loss of
      CSF due to the implanted pump catheter. The negativity of the routine headache
      test can exclude any leakage of CSF at the site of catheter insertion. SETTING:
      Anesthesia, Critical Care, and Multidisciplinary Pain Management Department,
      General University General Hospital, Valencia, Spain. RESULTS: Many patients are
      treated with implanted intrathecal infusion systems. In these patients, any
      neurological symptoms are readily attributed to the invasive neuroaxial system,
      especially severe cephalalgia. RICG was helpful in this particular case to make a
      diagnosis of exclusion of the diagnosis of SIH due to CSF leakage. CONCLUSION:
      RICG may be considered as an additional diagnostic technique in patients with
      chronic pain and implanted spinal infusion devices for whom standard detection
      procedures have been exhausted.

PMID- 24452662
TI  - Resolution of long standing tinnitus following radiofrequency ablation of C2-C3
      medial branches--a case report.
AB  - Tinnitus is described as an auditory phantom perception analogous to central
      neuropathic pain. Despite the high prevalence of this debilitating symptom, no
      intervention is recognized that reliably eliminates tinnitus symptoms; a cause
      has yet to be determined. A 65-year-old healthy man presented with a 3 year
      history of left-sided tinnitus. Full workup performed by the primary care
      physician including blood tests for electrolyte imbalance, consultations by 2
      independent otholaryngologists, and imaging did not reveal abnormalities to
      provide etiology of the tinnitus. No other complaints were noted except for
      occasional minimal left sided neck pain. Cervical spine x-ray showed degenerative
      changes with facet hypertrophy more pronounced on the left side. Subsequently,
      the patient underwent diagnostic left-sided C2-C3 medial branch block, resulting
      in complete resolution of tinnitus for more than 6 hours. After successful
      radiofrequency ablation of left C2-C3 medial branches, the patient became
      asymptomatic. At one year follow-up, he continued to be symptom free. Sparce
      studies have shown interaction between the somatosensory and auditory system at
      dorsal cochlear nucleus (DCN), inferior colliculus, and parietal association
      areas. Upper cervical nerve (C2) electrical stimulation evokes potentials in the
      DCN, eliciting strong patterns of inhibition and weak excitation of the DCN
      principal cells. New evidence demonstrated successful transcutaneous electrical
      nerve stimulation (TENS) of upper cervical nerve (C2) for treatment of somatic
      tinnitus in 240 patients. This case indicates that C2-C3 facet arthropathy may
      cause tinnitus and radiofrequency ablation of C2-C3 medial branches can provide
      an effective approach not previously considered. 

PMID- 24452663
TI  - Deactivation of distant pain-related regions induced by 20-day rTMS: a case study
      of one-week pain relief for long-term intractable deafferentation pain.
AB  - BACKGROUND: Deafferentation pain secondary to brachial plexus avulsion, spinal
      cord injury, and other peripheral nerve injuries is often refractory to
      conventional treatments. Stimulation of the primary motor cortex (M1) has been
      proven to be an effective treatment for intractable deafferentation pain. The
      mechanisms underlying the attenuation of deafferentation pain by motor cortex
      stimulation remain hypothetical. OBJECTIVES: The purpose of this case report is
      to: (1) summarize a case in which a patient suffering chronic intractable
      deafferentation pain for 25 years underwent rTMS treatment over M1, (2) describe
      the evidence from PET imaging, and (3) reveal a possible relief mechanism with
      cortical plasticity. STUDY DESIGN: Case report. SETTING: University hospital.
      RESULTS: This patient had successful pain control with no transient or lasting
      side effects. The pain relief remained stable for at least one week. At the end
      of the 20-day procedure, pain relief was obtained according to the Visual Analog
      Scale (VAS) (-34.6%) and the McGill Pain Questionnaire (MPQ) (-31.6%). In the
      PET/CT scans, the glucose metabolism was significantly reduced contralaterally to
      the pain side in the anterior cingulate cortex (ACC), insula, and caudate
      nucleus. There was no statistically significant difference in any other cortical
      area. LIMITATIONS: Single case of a patient with long-term intractable
      deafferentation pain having a PET study. CONCLUSION: This study implies that a
      single session of 20 Hz rTMS over the motor cortex could reduce the pain level in
      patients suffering from long-term, intractable deafferentation pain. The
      stimulation of the M1 induces deactivation in the ACC, insula, and caudate
      nucleus. The changes in these pain-related regions may mirror an adaptive
      mechanism to pain relief after rTMS treatment.

PMID- 24452665
TI  - Temporal decrease in overall antibiotic consumption accompanying antibiotic
      prescribing rate disclosure policy: evidence from analysis of national health
      insurance claims data in South Korea.
AB  - The health insurance review and assessment services, responsible for the
      assessment of quality and quantity of healthcare providers' services, implemented
      a public disclosure policy for antibiotic prescribing rate in February 2006. The
      aim of this study was to investigate changes of overall antibiotic consumption
      following the policy by analysing national healthcare utilization data from 2005
      to 2009. Prescription information of systemic antibiotics excluding antifungals
      and topical antibiotics was retrospectively collected from the population-based
      health insurance claims sample data for the five years from 2005 to 2009. Those
      data were analysed using the standardised anatomical therapeutic chemical/defined
      daily dose method. Antibiotic consumption was standardised by the defined daily
      dose per 1,000 inhabitants per day (DID). Descriptive statistics was used to
      present consumption figures for every year. Secondary comparison to other OECD
      countries based on published reports was added to weigh the antibiotic
      consumption level of South Korea in a global perspective. Overall antibiotic
      consumption decreased in 2006 (23.8 DID, 3.6 % decrease from 24.7 DID in 2005)
      and 2007 (21.5 DID, 9.7 % decrease from 2006), but rebounded in 2008 (24.3 DID,
      13 % increase from 2007) and 2009 (25.2 DID, 3.7 % increase from 2008). Temporal
      decreases in 2006 and 2007 were attributed to fewer prescriptions of penicillins
      (J01C group), among which the decrease in amoxicillin consumption was almost
      equal to that of overall antibiotic consumption. A similar fluctuation trend in
      overall antibiotic consumption occurred in the out-patient setting rather than
      the in-patient setting. Amoxicillin decreased since 2007, while
      amoxicillin/clavulanic acid, cefaclor and clarithromycin increased without
      dropping. The estimated antibiotic consumption level in this study was higher
      than the average of OECD countries, and the yearly fluctuation shown during the
      five years was a country specific pattern observed only in South Korea. Overall
      antibiotic consumption was temporarily decreased in 2006 and 2007. But this
      result might not signify an effect of government policy of antibiotic prescribing
      rate disclosure to the public. The results presented in DID unit, a more
      objective index than prescribing rates, suggest the need for further strategies
      to reduce antibiotic use nationwide. 

PMID- 24452666
TI  - Prehospital telemedicine electrocardiogram triage for a regional public emergency
      medical service: is it worth it? A preliminary cost analysis.
AB  - BACKGROUND: Telemedicine has been shown to improve quality of health-care
      delivery in several fields of medicine; its cost-effectiveness, however, is still
      a matter of debate. HYPOTHESIS: Pre-hospital telemedicine electrocardiogram
      triage for regional public emergency medical service may reduce costs. METHODS:
      An economic evaluation (cost analysis) was performed from the perspective of
      regional health-care system. Patients enrolled in the study and considered for
      cost analysis were those who called the local emergency medical service (EMS;
      dialing 1-1-8) during 2012 and underwent prehospital field triage with a
      telemedicine electrocardiogram (ECG) in the case of suspected acute cardiac
      disease (acute coronary syndrome, arrhythmia). The prehospital ECGs were read by
      a remote cardiologist, available 24/7. Cost savings associated with this method
      were calculated by subtracting the cost of prehospital triage with telemedicine
      support from the cost of conventional emergency department triage (ECG and
      consultation by a cardiologist). RESULTS: During 2012, the regional EMS performed
      109 750 ECGs by telemedicine support. The associated total cost for the regional
      health-care system was ?1 833 333, with a ?16.70 cost per single
      ECG/consultation. Given the cost of similar conventional emergency department
      treatment from a regional rate list of ?24.80 to ?55.20, the savings was ?8.10 to
      ?38.40 per ECG/consultation (total savings, ?891 759.50 to ?4 219 379.50). The
      cost for ruling out an acute cardiac disease was ?25.30; for a prehospital
      diagnosis of cardiovascular disease, ?49.20. With 629 prehospital diagnoses of ST
      elevation myocardial infarction and reported reductions in mortality thanks to
      prehospital diagnosis deduced from prior studies, 69 lives per year presumably
      could be saved, with a cost per quality-adjusted life year gained of ?1927,
      ?990/? - 2508 after correction for potential savings. CONCLUSIONS: Prehospital
      EMS triage with telemedicine ECG in patients with suspected acute cardiac disease
      may reduce health-care costs.

PMID- 24452667
TI  - Molecular evidence of kobuviruses in free-ranging red foxes (Vulpes vulpes).
AB  - Red foxes (Vulpes vulpes) are susceptible to viral diseases of domestic
      carnivores. In this study, by screening rectal swabs collected from 34 red foxes
      in Italy, we identified kobuvirus RNA in five samples. Based on analysis of
      partial RdRp and full-length VP1 genes, all of the strains shared the highest
      identity with canine kobuviruses (CaKVs) recently detected in the US, the UK and
      Italy. These findings provide the first evidence of the circulation of these
      novel viruses in foxes. 

PMID- 24452668
TI  - Chicken melanoma differentiation-associated gene 5 (MDA5) recognizes infectious
      bursal disease virus infection and triggers MDA5-related innate immunity.
AB  - The objective of the present study was to determine if chicken melanoma
      differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus
      (IBDV) infection to initiate and amplify an innate immune response in the chicken
      MDA5 (chMDA5) signaling pathway. Chicken embryo fibroblast DF-1 cells were
      infected with IBDV LP1 at a multiplicity of infection (MOI) of 0.5 or 10. In
      addition, knockdown and overexpression of chMDA5 were performed by transfecting
      DF-1 cells with chMDA5-targeting small interfering RNA (siRNA) or chMDA5
      expressing DNA. The transfected cells were infected with IBDV LP1 at an MOI of
      10. Cell culture supernatants and lysates were collected at 2, 8, 16 and 24 hours
      postinfection (hpi) for IBDV titer determination and RNA extraction,
      respectively. IBDV RNA loads and mRNA expression levels of chicken MDA5,
      interferon-beta (IFN-beta) promoter stimulator 1 (IPS-1), interferon regulatory
      factor-3 (IRF-3), IFN-beta, double-stranded RNA-dependent protein kinase (PKR),
      2',5'-oligoadenylate synthetase (OAS), myxovirus resistance gene (Mx), and major
      histocompatibility complex class I (MHC class I) were determined by real-time RT
      PCR. The IBDV titer increased up to 1.4 * 10(7) plaque-forming units (PFU)/mL at
      24 hpi, and the IBDV RNA load reached 464 ng/MUL at 24 hpi. The mRNA expression
      levels of chicken MDA5, IRF-3, IFN-beta, PKR, OAS, Mx and MHC class I in IBDV
      infected DF-1 cells exhibited significant (p < 0.05) upregulation up to 906-, 199
      , 26,310-, 12-, 66,144-, 64,039- and 33-fold, respectively. Expressed chMDA5 from
      transfection and double-stranded RNA from IBDV infection were localized or
      colocalized in the cytoplasm of DF-1 cells at 16 hpi. When chMDA5 was knocked
      down in DF-1 cells, IBDV titers and RNA loads were significantly higher (p <
      0.05) than those in DF-1 cells without chMDA5 knockdown at 24 hpi. The expression
      levels of chicken MDA5, IRF-3, IFN-beta and MHC class I in chMDA5-knockdown DF-1
      cells were significantly lower (p < 0.05) at 16 and 24 hpi. DF-1 cells
      overexpressing chMDA5 by transfection with chMDA5 expressing DNA had
      significantly lower (p < 0.05) IBDV titers and RNA loads at 16 and 24 hpi and
      showed significantly higher (p < 0.05) expression of chicken MDA5, IRF-3, IFN
      beta, PKR, OAS, Mx and MHC class I at 2 hpi. The results indicated that chicken
      MDA5 recognized IBDV infection and that this interaction resulted in the
      activation of chMDA5-related innate immune genes and upregulation of chicken MHC
      class I.

PMID- 24452670
TI  - Drug parity legislation: states, organizations seek to make oral cancer drugs
      more affordable.

PMID- 24452671
TI  - Most women have an inaccurate perception of their breast cancer risk.

PMID- 24452672
TI  - Breast cancer risk associated with HRT varies.

PMID- 24452673
TI  - An international phase 3 trial in head and neck cancer: quality of life and
      symptom results: EORTC 24954 on behalf of the EORTC Head and Neck and the EORTC
      Radiation Oncology Group.
AB  - BACKGROUND: The European Organization for Research and Treatment of Cancer
      (EORTC) 24954 phase 3 randomized clinical trial compared 2 schemes of combined
      chemotherapy for patients with resectable cancers of the hypopharynx and larynx:
      sequential induction chemotherapy and radiotherapy versus alternating
      chemoradiotherapy. The current study reports detailed effects of both treatment
      arms on health-related quality of life (HRQOL) and symptoms. METHODS: A total of
      450 patients aged 35 years to 76 years (World Health Organization performance
      status (WHO PS) <= 2) with untreated, resectable advanced squamous cell carcinoma
      of the larynx (tumor classification of T3-T4) or hypopharynx (tumor
      classification of T2-T3-T4) with regional lymph nodes in the neck classified as
      N0 to N2 with no metastases were randomized in this prospective phase 3 trial
      into either the sequential arm (control) or the alternating arm (experimental).
      QOL assessment was performed at randomization; at baseline; at 42 days; and at 6,
      12, 24, 36, and 48 months. RESULTS: There were no observed differences with
      regard to the primary endpoint of Fatigue and secondary endpoint of Dyspnea.
      Significant differences were found in the secondary endpoints of Swallowing and
      Speech problems at 42 days after randomization in favor of patients in the
      sequential arm. Explanatory and sensitivity analysis revealed that the primary
      analysis favored the sequential arm, but the majority of differences in HRQOL did
      not exist at the end of treatment, and returned to baseline levels. CONCLUSIONS:
      In the current study, a trend toward worse scores was noted in the patients
      treated on the alternating chemoradiotherapy arm but very few differences reached
      the level of statistical significance. The HRQOL scores of the majority of
      patients returned to baseline after therapy.

PMID- 24452674
TI  - What factors influence minority use of National Cancer Institute-designated
      cancer centers?
AB  - BACKGROUND: National Cancer Institute (NCI) cancer centers provide high-quality
      care and are associated with better outcomes. However, racial and ethnic minority
      populations tend not to use these settings. The current study sought to
      understand what factors influence minority use of NCI cancer centers. METHODS: A
      data set containing California Cancer Registry (CCR) data linked to patient
      discharge abstracts identified all patients with colorectal cancer (CRC) who were
      treated from 1996 through 2006. Multivariable models were generated to predict
      the use of NCI settings by race. Geographic proximity to an NCI center and
      patient sociodemographic and clinical characteristics were assessed. RESULTS:
      Approximately 5% of all identified patients with CRC (n = 79,231) were treated in
      NCI settings. The median travel distance for treatment for all patients in all
      hospitals was <= 5 miles. A higher percentage of minorities lived near an NCI
      cancer center compared with whites. A baseline multivariable model predicting use
      showed a negative association between Hispanic ethnicity and NCI center use (odds
      ratio, 0.71; 95% confidence interval, 0.64-0.79). Asian/Pacific Islander patients
      were more likely to use NCI centers (odds ratio, 1.41; 95% confidence interval,
      1.28-1.54). There was no difference in use noted among black patients. Increasing
      living distance from an NCI cancer center was found to be predictive of lower
      odds of use for all populations. Medicare and Medicaid insurance statuses were
      positively associated with NCI center use. Neighborhood-level education was found
      to be a more powerful predictor of NCI use than poverty or unemployment.
      CONCLUSIONS: Select minority groups underuse NCI cancer centers for CRC
      treatment. Sociodemographic factors and proximity to NCI centers are important
      predictors of use. Interventions to address these factors may improve minority
      attendance to NCI cancer centers for care.

PMID- 24452675
TI  - Clinical and economic outcomes of patients with brain metastases based on
      symptoms: an argument for routine brain screening of those treated with upfront
      radiosurgery.
AB  - BACKGROUND: Insurers have started to deny reimbursement for routine brain
      surveillance with magnetic resonance imaging (MRI) after stereotactic
      radiosurgery (SRS) for brain metastases in favor of symptom-prompted imaging. The
      authors investigated the clinical and economic impact of symptomatic versus
      asymptomatic metastases and related these findings to the use of routine brain
      surveillance. METHODS: Between January 2000 and December 2010, 442 patients
      underwent upfront SRS for brain metastases. In total, 127 asymptomatic patients
      and 315 symptomatic patients were included. Medical records were used to
      determine the presenting symptoms, distant and local brain failure, retreatment,
      and need for hospital and rehabilitative care. Cost-of-care estimates were based
      on Medicare payment rates as of January 2013. RESULTS: Symptomatic patients had
      an increased hazard for all-cause mortality (hazard ratio, 1.448) and were more
      likely to experience neurologic death (42% vs 20%; P < .0001). Relative to
      asymptomatic patients, symptomatic patients required more craniotomies (43% vs
      5%; P < .0001), had more prolonged hospitalization (2 vs 0 days; P < .0001), were
      more likely to have Radiation Therapy Oncology Group grade 3 and 4 post-treatment
      symptoms (24% vs 5%; P < .0001), and required $11,957 more on average to manage
      per patient. Accounting for all-cause mortality rates and the probability of
      diagnosis at each follow-up period, the authors estimated that insurers would
      save an average $1326 per patient by covering routine surveillance MRI after SRS
      to detect asymptomatic metastases. CONCLUSIONS: Patients who presented with
      symptomatic brain metastases had worse clinical outcomes and cost more to manage
      than asymptomatic patients. The current findings argue that routine brain
      surveillance after radiosurgery has clinical benefits and reduces the cost of
      care.

PMID- 24452676
TI  - Margin assessment in oral squamous cell carcinoma.

PMID- 24452677
TI  - Reply to margin assessment in oral squamous cell carcinoma.

PMID- 24452678
TI  - Epigenetic analysis of neurocognitive development at 1 year of age in a community
      based pregnancy cohort.
AB  - Multiple studies show that molecular genetic changes and epigenetic modifications
      affect the risk of cognitive disability or impairment. However, the role of
      epigenetic variation in cognitive development of neurotypical young children
      remains largely unknown. Using data from a prospective, community-based study of
      mother-infant pairs, we investigated the association of DNA methylation patterns
      in neonatal umbilical cord blood with cognitive and language development at 1
      year of age. No CpG loci achieved genome-wide significance, although a small
      number of weakly suggestive associations with Bayley-III Receptive Communication
      scales were noted. While umbilical cord blood is a convenient resource for
      genetic analyses of birth outcomes, our results do not provide conclusive
      evidence that its use for DNA methylation profiling yields epigenetic markers
      that are directly related to postnatal neurocognitive outcomes at 1 year of age.

PMID- 24452679
TI  - Induction of virulence gene expression in Staphylococcus aureus by pulmonary
      surfactant.
AB  - We performed a genomewide analysis using a next-generation sequencer to
      investigate the effect of pulmonary surfactant on gene expression in
      Staphylococcus aureus, a clinically important opportunistic pathogen. RNA
      sequence (RNA-seq) analysis of bacterial transcripts at late log phase revealed
      142 genes that were upregulated >2-fold following the addition of pulmonary
      surfactant to the culture medium. Among these genes, we confirmed by quantitative
      reverse transcription-PCR analysis that mRNA amounts for genes encoding ESAT-6
      secretion system C (EssC), an unknown hypothetical protein (NWMN_0246; also
      called pulmonary surfactant-inducible factor A [PsiA] in this study), and
      hemolysin gamma subunit B (HlgB) were increased 3- to 10-fold by the surfactant
      treatment. Among the major constituents of pulmonary surfactant, i.e.,
      phospholipids and palmitate, only palmitate, which is the most abundant fatty
      acid in the pulmonary surfactant and a known antibacterial substance, stimulated
      the expression of these three genes. Moreover, these genes were also induced by
      supplementing the culture with detergents. The induction of gene expression by
      surfactant or palmitate was not observed in a disruption mutant of the sigB gene,
      which encodes an alternative sigma factor involved in bacterial stress responses.
      Furthermore, each disruption mutant of the essC, psiA, and hlgB genes showed
      attenuation of both survival in the lung and host-killing ability in a murine
      pneumonia model. These findings suggest that S. aureus resists membrane stress
      caused by free fatty acids present in the pulmonary surfactant through the
      regulation of virulence gene expression, which contributes to its pathogenesis
      within the lungs of the host animal. 

PMID- 24452680
TI  - Targeting pili in enterococcal pathogenesis.
AB  - Passive protection, the administration of antibodies to prevent infection, has
      garnered significant interest in recent years as a potential prophylactic
      countermeasure to decrease the prevalence of hospital-acquired infections. Pili,
      polymerized protein structures covalently anchored to the peptidoglycan wall of
      many Gram-positive pathogens, are ideal targets for antibody intervention, given
      their importance in establishing infection and their accessibility to antibody
      interactions. In this work, we demonstrated that a monoclonal antibody to the
      major component of Enterococcus faecalis pili, EbpC, labels polymerized pilus
      structures, diminishes biofilm formation, and significantly prevents the
      establishment of a rat endocarditis infection. The effectiveness of this anti
      EbpC monoclonal provides strong evidence in support of its potential as a
      preventative. In addition, after radiolabeling, this monoclonal identified the
      site of enterococcal infection, providing a rare example of molecularly specific
      imaging of an established bacterial infection and demonstrating the versatility
      of this agent for use in future diagnostic and therapeutic applications. 

PMID- 24452681
TI  - CsrA (BB0184) is not involved in activation of the RpoN-RpoS regulatory pathway
      in Borrelia burgdorferi.
AB  - Borrelia burgdorferi encodes a homologue of the bacterial carbon storage
      regulator A (CsrA). Recently, it was reported that CsrA contributes to B.
      burgdorferi infectivity and is required for the activation of the central RpoN
      RpoS regulatory pathway. However, many questions concerning the function of CsrA
      in B. burgdorferi gene regulation remain unanswered. In particular, there are
      conflicting reports concerning the molecular details of how CsrA may modulate
      rpoS expression and, thus, how CsrA may influence the RpoN-RpoS pathway in B.
      burgdorferi. To address these key discrepancies, we examined the role of CsrA in
      differential gene expression in the Lyme disease spirochete. Upon engineering an
      inducible csrA expression system in B. burgdorferi, controlled hyperexpression of
      CsrA in a merodiploid strain did not significantly alter the protein and
      transcript levels of bosR, rpoS, and RpoS-dependent genes (such as ospC and
      dbpA). In addition, we constructed isogenic csrA mutants in two widely used
      infectious B. burgdorferi strains. When expression of bosR, rpoS, ospC, and dbpA
      was compared between the csrA mutants and their wild-type counterparts, no
      detectable differences were observed. Finally, animal studies indicated that the
      csrA mutants remained infectious for and virulent in mice. Analyses of B.
      burgdorferi gene expression in mouse tissues showed comparable levels of rpoS
      transcripts by the csrA mutants and the parental strains. Taken together, these
      results constitute compelling evidence that CsrA is not involved in activation of
      the RpoN-RpoS pathway and is dispensable for mammalian infectious processes
      carried out by B. burgdorferi. 

PMID- 24452682
TI  - Role of urinary cathelicidin LL-37 and human beta-defensin 1 in uncomplicated
      Escherichia coli urinary tract infections.
AB  - Cathelicidin (LL-37) and human beta-defensin 1 (hBD-1) are important components
      of the innate defense in the urinary tract. The aim of this study was to
      characterize whether these peptides are important for developing uncomplicated
      Escherichia coli urinary tract infections (UTIs). This was investigated by
      comparing urinary peptide levels of UTI patients during and after infection to
      those of controls, as well as characterizing the fecal flora of participants with
      respect to susceptibility to LL-37 and in vivo virulence. Forty-seven UTI
      patients and 50 controls who had never had a UTI were included. Participants were
      otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for
      fecal E. coli clones from patients and controls and were also compared based on
      phylotypes (A, B1, B2, and D). In vivo virulence was investigated in the murine
      UTI model by use of selected fecal isolates from patients and controls. On
      average, UTI patients had significantly more LL-37 in urine during infection than
      postinfection, and patient LL-37 levels postinfection were significantly lower
      than those of controls. hBD-1 showed similar urine levels for UTI patients and
      controls. Fecal E. coli isolates from controls had higher LL-37 susceptibility
      than fecal and UTI E. coli isolates from UTI patients. In vivo studies showed a
      high level of virulence of fecal E. coli isolates from both patients and controls
      and showed no difference in virulence correlated with the LL-37 MIC level. The
      results indicate that the concentration of LL-37 in the urinary tract and low
      susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay
      between host and pathogen attributes. 

PMID- 24452683
TI  - Phosphatidylinositol-specific phospholipase C contributes to survival of
      Staphylococcus aureus USA300 in human blood and neutrophils.
AB  - Staphylococcus aureus is an important human pathogen that employs a large
      repertoire of secreted virulence factors to promote disease pathogenesis. Many
      strains of S. aureus possess a plc gene that encodes a phosphatidylinositol (PI)
      specific phospholipase C (PI-PLC) capable of hydrolyzing PI and cleaving glycosyl
      PI (GPI)-linked proteins from cell surfaces. Despite being secreted by virulent
      staphylococci, the contribution of PI-PLC to the capacity of S. aureus to cause
      disease remains undefined. Our goal in these studies was to understand PI-PLC in
      the context of S. aureus biology. Among a collection of genetically diverse
      clinical isolates of S. aureus, community-associated methicillin-resistant S.
      aureus (CA-MRSA) USA300 secreted the most PI-PLC. Screening a collection of two
      component system (TCS) mutants of S. aureus, we identified both the agr quorum
      sensing system and the SrrAB TCS to be positive regulators of plc gene
      expression. Real-time PCR and PI-PLC enzyme assays of the TCS mutants, coupled
      with SrrA promoter binding studies, demonstrated that SrrAB was the predominant
      transcriptional activator of plc. Furthermore, plc regulation was linked to
      oxidative stress both in vitro and in vivo in a SrrAB-dependent manner. A
      Deltaplc mutant in a CA-MRSA USA300 background exhibited a survival defect in
      human whole blood and in isolated neutrophils. However, the same mutant strain
      displayed no survival defect in murine models of infection or murine whole blood.
      Overall, these data identify potential links between bacterial responses to the
      host innate immune system and to oxidative stress and suggest how PI-PLC could
      contribute to the pathogenesis of S. aureus infections. 

PMID- 24452684
TI  - Francisella tularensis Schu S4 lipopolysaccharide core sugar and O-antigen
      mutants are attenuated in a mouse model of tularemia.
AB  - The virulence factors mediating Francisella pathogenesis are being investigated,
      with an emphasis on understanding how the organism evades innate immunity
      mechanisms. Francisella tularensis produces a lipopolysaccharide (LPS) that is
      essentially inert and a polysaccharide capsule that helps the organism to evade
      detection by components of innate immunity. Using an F. tularensis Schu S4 mutant
      library, we identified strains that are disrupted for capsule and O-antigen
      production. These serum-sensitive strains lack both capsule production and O
      antigen laddering. Analysis of the predicted protein sequences for the disrupted
      genes (FTT1236 and FTT1238c) revealed similarity to those for waa (rfa)
      biosynthetic genes in other bacteria. Mass spectrometry further revealed that
      these proteins are involved in LPS core sugar biosynthesis and the ligation of O
      antigen to the LPS core sugars. The 50% lethal dose (LD50) values of these
      strains are increased 100- to 1,000-fold for mice. Histopathology revealed that
      the immune response to the F. tularensis mutant strains was significantly
      different from that observed with wild-type-infected mice. The lung tissue from
      mutant-infected mice had widespread necrotic debris, but the spleens lacked
      necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected
      mice had nominal necrosis, but the spleens had widespread necrosis. These data
      indicate that murine death caused by wild-type strains occurs by a mechanism
      different from that by which the mutant strains kill mice. Mice immunized with
      these mutant strains displayed >10-fold protective effects against virulent type
      A F. tularensis challenge. 

PMID- 24452685
TI  - MyD88- and TRIF-independent induction of type I interferon drives naive B cell
      accumulation but not loss of lymph node architecture in Lyme disease.
AB  - Rapidly after infection, live Borrelia burgdorferi, the causative agent of Lyme
      disease, is found within lymph nodes, causing rapid and strong tissue
      enlargement, a loss of demarcation between B cell follicles and T cell zones, and
      an unusually large accumulation of B cells. We sought to explore the mechanisms
      underlying these changes, as lymph tissue disruption could be detrimental for the
      development of robust Borrelia-specific immunity. A time course study
      demonstrated that the loss of the normal lymph node structure was a distinct
      process that preceded the strong increases in B cells at the site. The selective
      increases in B cell frequencies were due not to proliferation but rather to
      cytokine-mediated repositioning of B cells to the lymph nodes, as shown with
      various gene-targeted and bone marrow irradiation chimeras. These studies
      demonstrated that B. burgdorferi infection induced type I interferon receptor
      (IFNR) signaling in lymph nodes in a MyD88- and TRIF-independent manner and that
      type I IFNR indirect signaling was required for the excessive increases of naive
      B cells at those sites. It did not, however, drive the observed histopathological
      changes, which occurred independently also from major shifts in the lymphocyte
      homing chemokines, CXCL12, CXCL13, and CCL19/21, as shown by quantitative reverse
      transcription-PCR (qRT-PCR), flow cytometry, and transwell migration experiments.
      Thus, B. burgdorferi infection drives the production of type I IFN in lymph nodes
      and in so doing strongly alters the cellular composition of the lymph nodes, with
      potential detrimental effects for the development of robust Borrelia-specific
      immunity. 

PMID- 24452686
TI  - VgrG-5 is a Burkholderia type VI secretion system-exported protein required for
      multinucleated giant cell formation and virulence.
AB  - The type VI secretion system (T6SS) has emerged as a critical virulence factor
      for the group of closely related Burkholderia spp. that includes Burkholderia
      pseudomallei, B. mallei, and B. thailandensis. While the genomes of these
      bacteria, referred to as the Bptm group, appear to encode several T6SSs, we and
      others have shown that one of these, type VI secretion system 5 (T6SS-5), is
      required for virulence in mammalian infection models. Despite its pivotal role in
      the pathogenesis of the Bptm group, the effector repertoire of T6SS-5 has
      remained elusive. Here we used quantitative mass spectrometry to compare the
      secretome of wild-type B. thailandensis to that of a mutant harboring a
      nonfunctional T6SS-5. This analysis identified VgrG-5 as a novel secreted protein
      whose export depends on T6SS-5 function. Bioinformatics analysis revealed that
      VgrG-5 is a specialized VgrG protein that harbors a C-terminal domain (CTD)
      conserved among Bptm group species. We found that a vgrG-5 DeltaCTD mutant is
      avirulent in mice and is unable to stimulate the fusion of host cells, a hallmark
      of the Bptm group previously shown to require T6SS-5 function. The singularity of
      VgrG-5 as a detected T6SS-5 substrate, taken together with the essentiality of
      its CTD for virulence, suggests that the protein is critical for the effector
      activity of T6SS-5. Intriguingly, we show that unlike the bacterial-cell
      targeting T6SSs characterized so far, T6SS-5 localizes to the bacterial cell
      pole. We propose a model whereby the CTD of VgrG-5-, propelled by T6SS-5-, plays
      a key role in inducing membrane fusion, either by the recruitment of other
      factors or by direct participation. 

PMID- 24452687
TI  - Identification of point mutations in clinical Staphylococcus aureus strains that
      produce small-colony variants auxotrophic for menadione.
AB  - Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and
      relapsing infections that are difficult to diagnose and treat. Despite many years
      of study, the underlying molecular mechanisms and virulence effect of the small
      colony phenotype remain incompletely understood. We sequenced the genomes of five
      S. aureus SCV strains recovered from human patients and discovered previously
      unidentified nonsynonymous point mutations in three genes encoding proteins in
      the menadione biosynthesis pathway. Analysis of genetic revertants and
      complementation with wild-type alleles confirmed that these mutations caused the
      SCV phenotype and decreased virulence for mice. 

PMID- 24452688
TI  - Incorporation of phosphorylcholine into the lipooligosaccharide of nontypeable
      Haemophilus influenzae does not correlate with the level of biofilm formation in
      vitro.
AB  - Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that
      causes otitis media in children and community-acquired pneumonia or exacerbations
      of chronic obstructive pulmonary disease in adults. A large variety of studies
      suggest that biofilm formation by NTHi may be an important step in the
      pathogenesis of this bacterium. The objective of this report was to determine the
      relationship between the presence of phosphorylcholine in the lipooligosaccharide
      of NTHi and the level of biofilm formation. The study was performed on 111 NTHi
      clinical isolates collected from oropharyngeal samples of healthy children,
      middle ear fluid of children with otitis media, and sputum samples of patients
      with chronic obstructive pulmonary disease or community-acquired pneumonia. NTHi
      clinical isolates presented a large variation in the level of biofilm formation
      in a static assay and phosphorylcholine content. Isolates collected from the
      oropharynx and middle ear fluid of children tended to have more phosphorylcholine
      and made denser biofilms than isolates collected from sputum samples of patients
      with chronic obstructive pulmonary disease or community-acquired pneumonia. No
      correlation was observed between biofilm formation and the presence of
      phosphorylcholine in the lipooligosaccharide for either planktonic or biofilm
      growth. This lack of correlation was confirmed by abrogating phosphorylcholine
      incorporation into lipooligosaccharide through licA gene deletion, which had
      strain-specific effects on biofilm formation. Altogether, we present strong
      evidence to conclude that there is no correlation between biofilm formation in a
      static assay and the presence of phosphorylcholine in lipooligosaccharide in a
      large collection of clinical NTHi isolates collected from different groups of
      patients. 

PMID- 24452690
TI  - Efficacy and safety of patent foramen ovale closure in patients with a
      cryptogenic stroke: Systematic review and meta-analysis.

PMID- 24452689
TI  - Neutrophils select hypervirulent CovRS mutants of M1T1 group A Streptococcus
      during subcutaneous infection of mice.
AB  - Pathogen mutants arise during infections. Mechanisms of selection for pathogen
      variants are poorly understood. We tested whether neutrophils select mutations in
      the two-component regulatory system CovRS of group A Streptococcus (GAS) during
      infection using the lack of production of the protease SpeB (SpeB activity
      negative [SpeB(A-)]) as a marker. Depletion of neutrophils by antibodies RB6-8C5
      and 1A8 reduced the percentage of SpeB(A-) variants (SpeB(A-)%) recovered from
      mice infected with GAS strain MGAS2221 by >76%. Neutrophil recruitment and SpeB(A
      )% among recovered GAS were reduced by 95% and 92%, respectively, in subcutaneous
      MGAS2221 infection of CXCR2(-/-) mice compared with control mice. In air sac
      infection with MGAS2221, levels of neutrophils and macrophages in lavage fluid
      were reduced by 49% and increased by 287%, respectively, in CXCR2(-/-) mice
      compared with control mice, implying that macrophages play an insignificant role
      in the reduction of selection for SpeB(A-) variants in CXCR2(-/-) mice. One
      randomly chosen SpeB(A-) mutant outcompeted MGAS2221 in normal mice but was
      outcompeted by MGAS2221 in neutropenic mice and had enhancements in expression of
      virulence factors, innate immune evasion, skin invasion, and virulence. This and
      nine other SpeB(A-) variants from a mouse all had nonsynonymous covRS mutations
      that resulted in the SpeB(A-) phenotype and enhanced expression of the CovRS
      controlled secreted streptococcal esterase (SsE). Our findings are consistent
      with a model that neutrophils select spontaneous covRS mutations that maximize
      the potential of GAS to evade neutrophil responses, resulting in variants with
      enhanced survival and virulence. To our knowledge, this is the first report of
      the critical contribution of neutrophils to the selection of pathogen variants. 

PMID- 24452691
TI  - Transplanting neural progenitors into a complete transection model of spinal cord
      injury.
AB  - Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy
      for spinal cord injury (SCI) because of the potential for cell replacement and
      restoration of connectivity. Our previous studies have shown that transplants of
      NPC, composed of neuron- and glia-restricted progenitors derived from the
      embryonic spinal cord, survived well in partial lesion models and generated graft
      derived neurons, which could be used to form a functional relay. We have now
      examined the properties of a similar NPC transplant using a complete transection
      model in juvenile and adult rats. We found poor survival of grafted cells despite
      using a variety of lesion methods, matrices, and delays of transplantation. If,
      instead of cultured progenitor cells, the transplants were composed of segmental
      or dissociated segments of fetal spinal cord (FSC) derived from similar-staged
      embryos, grafted cells survived and integrated well with host tissue in juvenile
      and adult rats. FSC transplants differentiated into neurons and glial cells,
      including astrocytes and oligodendrocytes. Graft-derived neurons expressed
      glutaminergic and GABAergic markers. Grafted cells also migrated and extended
      processes into host tissue. Analysis of axon growth from the host spinal cord
      showed serotonin-positive fibers and biotinylated dextran amine-traced
      propriospinal axons growing into the transplants. These results suggest that in
      treating severe SCI, such as complete transection, NPC grafting faces major
      challenges related to cell survival and formation of a functional relay. Lessons
      learned from the efficacy of FSC transplants could be used to develop a
      therapeutic strategy based on neural progenitor cells for severe SCI.

PMID- 24452692
TI  - Reverse total shoulder arthroplasty after failed deltoid flap reconstruction.
AB  - HYPOTHESIS: Reverse shoulder arthroplasty (RSA) yields unsatisfactory results
      after deltoid flap reconstruction due to defect of the deltoid muscle. METHODS:
      We retrospectively reviewed the outcome of 19 patients after failed deltoid flap
      reconstruction treated with RSA. Follow-up was after a mean of 4.5 years.
      RESULTS: Seven patients (37 %) had nine postoperative complications requiring
      totally 16 revision surgeries. Nonetheless, at latest follow-up, 17 patients had
      no or mild, two had moderate, and none had severe pain. Before RSA; 13 patients
      had a pseudoparesis. At latest follow-up, none of the patients had a
      pseudoparesis. Mean flexion was 121 degrees  (90 degrees -160 degrees ).
      Abduction strength averaged 2.3 kg (range 0-5.4 kg). The mean constant score was
      70 % (range 28-98 %). Of the 19 patients, 15 were very satisfied with the
      outcome, four were satisfied, and none was dissatisfied. The mean overall
      subjective shoulder value was 73 % (30-95 %) of the value of a normal shoulder.
      CONCLUSIONS: Despite of a localized defect of the deltoid muscle after deltoid
      flap repair, RSA can reliably be associated with a satisfactory outcome.

PMID- 24452693
TI  - Addition of the Akt inhibitor triciribine overcomes antibody resistance in cells
      from ErbB2/Neu-positive/PTEN-deficient mammary tumors.
AB  - Trastuzumab resistance is a challenging problem in ErbB2/HER2-positive breast
      cancers. Multiple mechanisms of resistance have been proposed and, thus, may
      require the development of more personalized therapies. In this study, we report
      the establishment of a mouse mammary cancer cell line, designated MT104T,
      obtained from spontaneous tumors in genetically engineered FVB/N-ErbB2/Neu
      positive-PTEN-deficient mice. The critical molecular phenotype of MT104T cells
      was confirmed by genotyping and western blot analysis. This cell line was
      tumorigenic in immunologically intact syngeneic mice, forming tumors of generally
      similar histology as its origin. PTEN loss led to hyperactivation of Akt and
      conferred resistance to anti-ErbB2/Neu antibody treatment in MT104T cells.
      Addition of the Akt inhibitor triciribine (TCN) inhibited the viability of MT104T
      cells in a dose- and time-dependent manner as evaluated by MTT assay. ErbB2/Neu
      antibody and TCN combination treatment greatly induced apoptosis of MT104T cells
      as indicated by Annexin V-FITC staining. Moreover, this combination treatment
      also significantly reduced both Akt and Erk activities, which are responsible for
      the inhibitory effect on MT104T cells. Therefore, MT104T cells could represent an
      alternative model system to investigate the nature of ErbB2-positive breast
      cancer and for the experimental therapeutics studies of this disease. Our
      findings also suggest that combination of TCN may be a potential strategy for the
      treatment of trastu-zumab-resistant breast cancer mediated by PTEN loss or PI3K
      hyperactivation, which may facilitate the development of more personalized
      therapies for breast cancer patients. 

PMID- 24452694
TI  - Hemicrania continua.
AB  - In recent years, hemicrania continua has become a well-recognized primary
      headache disorder known for its chronicity and resulting disability in a subset
      of patients with headache. The core clinical features have been well described:
      unilateral, side-locked headaches that are continuous (although interrupted by
      frequent severe exacerbations), associated with autonomic symptoms and a response
      to indomethacin. However, areas of relative controversy remain in its
      classification and diagnosis. Several relatively large case series have better
      delineated the associated features of this disorder, including atypical
      presentations. Recently, neuroimaging research has provided new insights into the
      underlying pathways involved in the disorder, in particular activation of the
      contralateral posterior hypothalamus and the ipsilateral dorsal rostral pons.
      Despite its well-known response to indomethacin, many patients still endure long
      delays in the appropriate diagnosis and treatment. There remains a need for new
      treatments given the morbidity associated with long-term indomethacin use. 

PMID- 24452695
TI  - Hybrid pn-junction solar cells based on layers of inorganic nanocrystals and
      organic semiconductors: optimization of layer thickness by considering the width
      of the depletion region.
AB  - We report the formation and characterization of hybrid pn-junction solar cells
      based on a layer of copper diffused silver indium disulfide (AgInS2@Cu)
      nanoparticles and another layer of copper phthalocyanine (CuPc) molecules. With
      copper diffusion in the nanocrystals, their optical absorption and hence the
      activity of the hybrid pn-junction solar cells was extended towards the near-IR
      region. To decrease the particle-to-particle separation for improved carrier
      transport through the inorganic layer, we replaced the long-chain ligands of
      copper-diffused nanocrystals in each monolayer with short-ones. Under
      illumination, the hybrid pn-junctions yielded a higher short-circuit current as
      compared to the combined contribution of the Schottky junctions based on the
      components. A wider depletion region at the interface between the two active
      layers in the pn-junction device as compared to that of the Schottky junctions
      has been considered to analyze the results. Capacitance-voltage characteristics
      under a dark condition supported such a hypothesis. We also determined the width
      of the depletion region in the two layers separately so that a pn-junction could
      be formed with a tailored thickness of the two materials. Such a "fully-depleted"
      device resulted in an improved photovoltaic performance, primarily due to
      lessening of the internal resistance of the hybrid pn-junction solar cells. 

PMID- 24452696
TI  - Estrous cycle and sex affect cocaine-induced behavioural changes in CD1 mice.
AB  - RATIONALE: Several findings on sex differences in cocaine response suggest a role
      for hormonal milieu in modulating the subjective effects of cocaine. Nitric oxide
      (NO) has been involved in the neurochemical, hormonal, and behavioral changes
      related to stress and anxiety. Within the brain, the anteroventral subdivision of
      the medial amygdala (MeAV) is an important area involved in processing emotional
      responses such as anxiety and a high density of NO-producing neurons is observed
      in this area. OBJECTIVES: In this study, we hypothesize the possibility of
      sex/hormonal differences in response to cocaine and that these differences may
      reflect a change in the MeAV nitrergic system. We have examined cocaine's acute
      effects on nicotinamide adenine dinucleotide phosphate diaphorase (nadph-d)
      expression, as well as its effect on motor activity and anxiety in male and
      estrus and diestrus females. RESULTS: Our results show that acute cocaine
      administration produces an increase in both anxiety behaviors and nadph-d
      expression in the MeAV. Male and diestrus female mice were more susceptible to
      these effects of cocaine than estrus female mice in which no differences were
      detected. In addition, we examined individual differences in male and female mice
      responding to intravenous cocaine reinforcement in a self-administration
      paradigm. Female mice acquired cocaine self-administration at a faster rate than
      males and showed a higher motivation to self-administer cocaine under a
      progressive ratio schedule of reinforcement. CONCLUSIONS: Our data suggest a
      complex interaction between hormonal milieu and the behavioral and reinforcing
      effects of cocaine.

PMID- 24452698
TI  - Downregulation of NOB1 suppresses the proliferation and tumor growth of non-small
      cell lung cancer in vitro and in vivo.
AB  - Non-small cell lung cancer (NSCLC) is a lethal disease due to the absence of
      effective diagnostic biomarkers and therapeutic targets. Therefore, novel
      molecular targets are critically needed to formulate new approaches for this
      devastating disease. In the present study, using quantitive real-time PCR and
      immunohistochemistry. we initially found that expression of the ribosome assembly
      factor NIN/RPN12 binding protein (NOB1) was elevated in the majority of NSCLC
      tissues when compared to that in the normal lung tissue counterparts, and its
      expression level was correlated with key pathological characteristics including
      tumor differentiation, stage and metastasis. Then, the recombinant lentiviral
      shRNA expression vector carrying NOB1 was constructed and infected into the human
      NSCLC A549 cell line. Cell proliferation, cell apoptosis, cell cycle distribution
      and colony formation ability in A549 cells were assessed following downregulation
      of NOB1 by siRNA. In addition, tumor growth ability in nude mice was evaluated to
      define the function of NOB1 in cell transformation and tumorigenesis. It was
      found that downregulation of NOB1 expression using the RNA silencing approach in
      A549 tumor cells significantly suppressed the proliferation and colony formation
      ability, and induced tumor apoptosis in vitro. Tumor growth was also suppressed
      in vivo. These data suggest that NOB1 is an important regulator of the
      tumorigenic properties of human NSCLC and may be used as a new promising
      diagnostic biomarker and a potential anticancer therapeutic target for NSCLC. 

PMID- 24452699
TI  - Short- and long-term changes in perceived work ability after interdisciplinary
      rehabilitation of chronic musculoskeletal disorders: prospective cohort study
      among 854 rehabilitants.
AB  - OBJECTIVE: To investigate the changes in rehabilitants' perceived work ability
      after rehabilitation for chronic musculoskeletal disorders with respect to the
      baseline characteristics. DESIGN: Prospective cohort study based on register and
      repeated survey data. SETTING: Public sector employees in ten towns and five
      hospital districts. SUBJECTS: A total of 854 employees who participated in the
      rehabilitation programme owing to common chronic musculoskeletal disorders
      between 1997 and 2009. INTERVENTIONS: Interdisciplinary, biopsychosocial,
      inpatient rehabilitation programme targeting people of working age with common
      chronic musculoskeletal disorders. The programme was executed in different
      rehabilitation centres across the country and funded by the Social Insurance
      Institution of Finland. MAIN MEASURES: Differences in perceived work ability
      level before and after rehabilitation. Data were derived from repeated surveys on
      average 2.1 years before rehabilitation, and 1.5 years (short-term follow-up) and
      6.0 years (long-term follow-up) after rehabilitation. RESULTS: Before the
      rehabilitation, perceived work ability was 7.13 (SD 1.84) among the rehabilitants
      and 7.27 (SD 1.72) in the matched reference population. Among rehabilitants, this
      figure decreased by 0.82 (95% confidence interval -0.98 to -0.67) in the short
      term and by 1.26 (95% confidence interval -1.45 to -1.07) in the long-term follow
      up. Only slight differences in steepness of this deterioration were observed
      between subgroups, created based on the participants' baseline characteristics.
      CONCLUSIONS: Perceived work ability of participants, in an interdisciplinary
      biopsychosocial rehabilitation programme for common musculoskeletal disorders,
      deteriorated regardless of any studied pretreatment characteristics. The
      improvement of work ability may be an unrealistic goal for participants in this
      type of rehabilitation.

PMID- 24452697
TI  - Effects of psychotropic drugs on second messenger signaling and preference for
      nicotine in juvenile male mice.
AB  - RATIONALE: A common treatment strategy for pediatric attention
      deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) is
      combined methylphenidate (MPH) and fluoxetine (FLX). This has raised concerns
      because MPH + FLX treatment may have pharmacodynamic properties similar to
      cocaine, potentially increasing drug abuse liability. OBJECTIVES: To examine the
      short- and long-term consequences of repeated vehicle, MPH, FLX, MPH + FLX, and
      cocaine treatment on gene expression in juvenile (postnatal days [PD] 20-34) and
      adult (PD 70-84) male mice. We further assessed whether juvenile drug treatment
      influenced subsequent sensitivity for nicotine in adulthood. METHODS: Juvenile
      and adult C57BL/6J mice received vehicle, MPH, FLX, MPH + FLX, or cocaine twice
      daily for 15 consecutive days. Mice were sacrificed 24 h or 2 months after the
      last drug injection to assess drug-induced effects on the extracellular signal
      regulated protein kinase-1/2 (ERK) pathway within the ventral tegmental area.
      Subsequent sensitivity for nicotine (0.05, 0.07, and 0.09 mg/kg) was measured
      using the place-conditioning paradigm (CPP) 24 h and 2 months after juvenile drug
      exposure. RESULTS: MPH + FLX, or cocaine exposure in juvenile mice increased mRNA
      expression of ERK2 and its downstream targets (CREB, cFos, and Zif268), and
      increased protein phosphorylation of ERK2 and CREB 2 months after drug exposure.
      Similar mRNA findings were observed in the adult-treated mice. Findings on gene
      expression 24 h following drug treatment were variable. Juvenile drug exposure
      increased preference for nicotine when tested in adulthood. CONCLUSIONS: Early
      life MPH + FLX, or cocaine exposure similarly disrupts the ERK pathway, a
      signaling cascade implicated in motivation and mood regulation, and increases
      sensitivity for nicotine in adulthood.

PMID- 24452700
TI  - Immediate effects of two attention strategies on trunk control on patients after
      stroke. A randomized controlled pilot trial.
AB  - OBJECTIVE: To compare the immediate effects of an external focus to enhance
      lateral body weight shift after stroke. DESIGN: Randomized controlled trial.
      SETTING: Inpatient rehabilitation hospital. SUBJECTS: Twenty patients after
      stroke (11 males; mean (SD) age 72.2 (7.4) years; duration of illness 56 (14)
      days; there were 9 (45%) left-sided strokes) with impaired sitting balance were
      randomly allocated into two groups either external focus (n = 10) or internal
      focus (n = 10). INTERVENTION: Patients in the external focus group, while
      sitting, were instructed to shift as much weight as they could sidewards to an
      external point next to their hip. Patients in the internal focus group were
      instructed to shift as much weight as they could sidewards to their hip. MAIN
      OUTCOME MEASURES: Immediate lateral body weight shift as well as anterior
      posterior deviation was measured in centimetres with a sensor mat. RESULTS:
      Patients in the external focus group achieved greater lateral body weight shift
      than those in the internal focus group (mean shift (SD) 8.7 (2.6) cm vs. 4.5
      (3.3) cm, respectively; P = 0.006). However, there were no significant
      differences in anterior-posterior deviation (mean shift (SD) 2.3 (1.3) cm vs. 1.2
      (1.2) cm, respectively; P = 0.08). CONCLUSION: Using an external focus may lead
      immediately to an enhanced lateral body weight shift while sitting, without
      increasing anterior-posterior deviation.

PMID- 24452701
TI  - A randomized controlled trial of the effectiveness of handheld computers for
      improving everyday memory functioning in patients with memory impairments after
      acquired brain injury.
AB  - OBJECTIVE: To determine the effectiveness of personal digital assistant devices
      on achievement of memory and organization goals in patients with poor memory
      after acquired brain injury. DESIGN: Assessor blinded randomized controlled
      trial. SETTING: Specialist brain injury rehabilitation hospital (inpatients and
      outpatients). PARTICIPANTS: Adults with acquired brain impairments (85% traumatic
      brain injury; aged >=17 years) who were assessed as having functional memory
      impairment on the Rivermead Behavioural Memory Test (General Memory Index).
      INTERVENTIONS: Training and support to use a personal digital assistant for eight
      weeks to compensate for memory failures by an occupational therapist. The control
      intervention was standard rehabilitation, including use of non-electronic memory
      aids. MAIN OUTCOME MEASURES: Goal Attainment Scale which assessed achievement of
      participants' daily memory functioning goals and caregiver perception of memory
      functioning; and General Frequency of Forgetting subscale of the Memory
      Functioning Questionnaire administered at baseline (pre-randomization) and post
      intervention (eight weeks later). RESULTS: Forty-two participants with memory
      impairment were recruited. Use of a personal digital assistant led to greater
      achievement of functional memory goals (mean difference 1.6 (95% confidence
      interval (CI) 1.0 to 2.2), P = 0.0001) and improvement on the General Frequency
      of Forgetting subscale (mean difference 12.5 (95% CI 2.0 to 22.9), P = 0.021).
      CONCLUSIONS: Occupational therapy training in the use of a handheld computer
      improved patients' daily memory function more than standard rehabilitation.

PMID- 24452702
TI  - The Restore4Stroke self-management intervention 'Plan ahead!': rationale and
      description of the treatment protocol based on proactive action planning.
AB  - OBJECTIVE: To describe the rationale behind and description of a group-based self
      management intervention developed for stroke patients and their partners.
      RATIONALE: Based on the assumption that proactive coping strategies are
      beneficial for the re-uptake of daily life by stroke patients and partners, we
      developed a new stroke-specific, group-based self-management intervention based
      on proactive action planning. A first concept of the treatment protocol was
      developed based on the proactive coping theory, the Health Action Process
      Approach model, existing interventions and expert consultations. Further
      adjustments were based on two pilot studies, including addition of solution-based
      therapeutic techniques. DESCRIPTION OF THE INTERVENTION: 'Plan ahead!' is a 10
      week group-based self-management intervention, consisting of six 2-hour sessions
      in the first six weeks and a 2-hour booster session in the 10th week. It is
      offered in an outpatient setting by two rehabilitation professionals with
      experience in group counselling and working with stroke patients. It is provided
      to groups of four stroke patients living at home (stroke >=2 months ago) and
      their partners. The main features are (1) proactive action planning as the main
      constituent, (2) stroke-specific elements and (3) considering partners as full
      participants. DISCUSSION: This stroke-specific intervention is expected to
      increase the use of proactive action planning and thus improve the participation
      of stroke patients and their partners. It is innovative in its aim to change
      behaviour patterns of participants directly, teaching participants a general
      action planning strategy and considering partners as full participants with their
      own goals and opportunities.

PMID- 24452703
TI  - The Needs and Provision Complexity Scale: a first psychometric analysis using
      multicentre data.
AB  - OBJECTIVE: A psychometric evaluation of the Needs and Provision Complexity Scale
      (NPCS). MAIN MEASURE: The NPCS is designed to evaluate both needs for health and
      social support (NPCS-Needs) and services provided to meet those needs (NPCS
      Gets). DESIGN: A consecutive cohort of patients were recruited from nine
      specialist neurorehabilitation units in London. SUBJECTS: Four hundred and twenty
      eight patients were assessed at discharge (63.1% males; mean age 49 years) of
      whom 73.6% had acquired brain injury (49.5% stroke/subarachnoid, 14.7% traumatic
      brain injury, 9.3% 'other acquired brain injury'), 8.9% spinal cord injury, 6.1%
      peripheral neuropathy, 4.9% progressive neurological and 6.3% other neurological
      conditions. RESULTS: The NPCS-Needs was completed by the clinical team at
      discharge and 212 patients reported NPCS-Gets after six months. NPCS-Gets
      repeatability was tested in a subsample (n = 60). Factor analysis identified two
      principal domains ('Health and personal care' and 'Social care and support')
      accounting for 66% of variance, and suggested a large general factor underpinning
      the NPCS. Internal consistency was high (alpha = 0.94) and repeatability
      acceptable. Intraclass coefficients for domain scores were healthcare 0.67 (95%
      confidence interval (CI) 0.48-0.80); personal care 0.83 (0.73-0.90);
      rehabilitation 0.65 (0.45-0.78); social/family support 0.66 (0.46-0.79) and
      environment 0.84 (0.74-0.90). Linear-weighted kappas for item-by-item agreement
      ranged from 0.42 to 0.83. Concurrent validity was demonstrated through
      correlations with measures of dependency and community integration. CONCLUSIONS:
      Notwithstanding a 50% response rate after six months, the NPCS has good internal
      consistency, a robust two-factor structure, acceptable test-retest reliability
      and initial evidence of concurrent validity.

PMID- 24452704
TI  - Does botulinum toxin injection site determine outcome in post-stroke
      plantarflexion spasticity? Comparison study of two injection sites in the
      gastrocnemius muscle: a randomized double-blind controlled trial.
AB  - OBJECTIVE: To determine if botulinum toxin type A injection at the proximal 2/10
      and 3/10 of calf length, where the intramuscular nerve endings of the
      gastrocnemius muscle are densely distributed, is more efficacious in controlling
      plantarflexion spasticity than injection at distant sites within the same muscle.
      DESIGN: A double-blind randomized controlled trial. SETTTING: Two rehabilitation
      centres. SUBJECTS: Forty stroke patients were randomly allocated to two groups.
      Group A received injection at the proximal 2/10 and 3/10 of calf length, group B
      at and below the midbelly of the muscle. Both groups received 200 IU of botulinum
      toxin A and were followed up to eight weeks. MAIN MEASURES: Primary variables
      were the surface electromyography values recorded during plantarflexion;
      secondary variables were the Modified Ashworth Scale, Modified Tardieu Scale,
      clonus scale, 10-metre walking test, ABILOCO and Functional Ambulation
      Categories. RESULTS: At baseline, the median Modified Ashworth Scale was 2.0
      (range,1+ -3.0), and there were no significant differences between the two groups
      in all the parameters, including spasticity. Compared to baseline, no significant
      differences between the two groups were detected in all the surface
      electromyography and clinical parameters at week 8 (P > 0.05). Both groups showed
      significant improvement of spasticity with a median Modified Ashworth Scale of 1+
      (range, 0.0-2.0) at eight weeks. CONCLUSIONS: Botulinum toxin A injection was
      associated with a significant improvement from baseline to week 8 in both
      treatment groups, however, no significant difference between the 2 groups was
      observed, based on the electrophysiological and clinical parameters employed in
      this study.

PMID- 24452705
TI  - Group memory rehabilitation for people with multiple sclerosis: a feasibility
      randomized controlled trial.
AB  - OBJECTIVE: To assess the feasibility and effectiveness of a group memory
      rehabilitation programme combining compensation and restitution strategies.
      DESIGN: Randomized controlled trial. SETTING: Community. PARTICIPANTS: People
      with multiple sclerosis who reported memory difficulties were recruited.
      INTERVENTIONS: A group memory rehabilitation programme, comprising ten 1.5-hour
      sessions, was compared with a waiting list control. MAIN MEASURES: The primary
      outcome was the Everyday Memory Questionnaire. Secondary outcomes included the
      General Health Questionnaire 28 and MS Impact Scale administered four and eight
      months after randomization. In addition, those in the intervention group gave
      feedback about the intervention. RESULTS: Forty-eight participants were
      recruited. They were aged 34-72 years (mean 54.3, SD 11.0) and 33 (69%) were
      women. There were no significant differences between the two groups on the
      Everyday Memory Questionnaire or MS Impact Scale (P > 0.05) at four or eight
      months after randomization. However, the intervention group reported
      significantly better mood than controls on the GHQ-28 at eight months (P = 0.04).
      Participants showed minimal benefit from the memory rehabilitation programme on
      quantitative measures but the intervention was well received, as indicated by
      positive feedback at the end of the intervention. CONCLUSIONS: There was no
      significant effect of the intervention on memory but there was a significant
      effect on mood. The results suggest a larger scale study is justified.

PMID- 24452706
TI  - Effect on arm function and cost of robot-assisted group therapy in subacute
      patients with stroke and a moderately to severely affected arm: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness and efficiency of robot-assisted arm
      group therapy (RAGT) versus individual arm therapy (IAT) to restore motor
      function in the moderately to severely affected patient after stroke. DESIGN:
      Single blind randomized controlled trial. SETTING: Two in-patient neurological
      rehabilitation centers. PARTICIPANTS: Fifty first time subacute patients with
      stroke and a non-functional hand. INTERVENTION: The patients practiced either 30
      minutes of RAGT + 30 minutes of IAT (group A) or 2x30 minutes of IAT (group B),
      per workday for four weeks. The RAGT consisted of six workstations enabling
      repetitive practice of finger, wrist, forearm and shoulder movements. Patients
      practiced according to their impairment level on at least two workstations per
      session. The IAT followed the Motor Relearning Programme, enriched by elements of
      the impairment-oriented training. MAIN OUTCOME MEASURE: Changes of the Fugl Meyer
      Score (FM, 0-66) between baseline and after 4 weeks, incremental cost
      effectiveness. RESULTS: Patients were homogeneous at study onset. All patients
      improved their upper limb motor function over time, but there were no between
      group differences. The initial (terminal) FM scores were 14.6+/-9.4 (25.7+/-16.5)
      in group A and 16.5+/-9.8 (31.1+/-19.1) in group B. The treatment of a single
      patient with RAGT cost 4.15 ?, compared to 10.00 ? for a patient to receive IAT.
      CONCLUSION: RAGT in combination with IAT was equally effective as a double
      session of IAT regarding the restoration of upper limb motor functions in
      moderate to severely affected subacute patients with stroke. The treatment costs
      for RAGT were less.

PMID- 24452707
TI  - Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and
      challenges in treating headache.
AB  - A role for calcitonin gene-related peptide (CGRP) in the pathophysiology of
      migraine has been established over the past 25 years. There have now been at
      least five different small-molecule CGRP antagonists that have demonstrated
      statistical proof of efficacy in the acute treatment of migraine. At present,
      multiple clinical trials are underway that are assessing the ability of long
      acting antibodies against CGRP to prevent frequent migraine attacks. This review
      summarizes the existing data concerning the role of CGRP in migraine and attempts
      to highlight some possible outcomes from the ongoing anti-CGRP antibody trials. 

PMID- 24452709
TI  - The role of charge transfer in the energy level alignment at the pentacene/C60
      interface.
AB  - Understanding the mechanism of energy level alignment at organic-organic
      interfaces is a crucial line of research to optimize applications in organic
      electronics. We address this problem for the C60-pentacene interface by
      performing local-orbital Density Functional Theory (DFT) calculations, including
      the effect of the charging energies on the energy gap of both organic materials.
      The results are analyzed within the induced density of interface states (IDIS)
      model. We find that the induced interface potential is in the range of 0.06-0.10
      eV, in good agreement with the experimental evidence, and that such potential is
      mainly induced by the small, but non-negligible, charge transfer between the two
      compounds and the multipolar contribution associated with pentacene. We also
      suggest that an appropriate external intercompound potential could create an
      insulator-metal transition at the interface. 

PMID- 24452710
TI  - Bacopa monnieri (L.) exerts anti-inflammatory effects on cells of the innate
      immune system in vitro.
AB  - Bacopa monnieri (L., BM) is a traditional Ayurvedic medicinal herb recognised for
      its efficacy in relieving acute pain and inflammation, as related to selective
      inhibition of cyclo-oxygenase-2 (COX-2) enzyme and consequent reduction in COX-2
      mediated prostanoid mediators. BM is also associated with cognitive enhancing
      (nootropic) activity including improving memory free recall, observed after
      prolonged intake (>3 months). It is likely that the time frame required to exert
      an effect in the brain reflects regulation by BM of chronic inflammation and
      oxidative stress associated with aging and chronic diseases, and other
      polypharmacological effects. We report down-regulation by BM of NO and TNF-alpha
      in stimulated RAW 246.7 macrophages and of IFN-gamma in stimulated human blood
      cells. Furthermore, in human blood cells, IL-10 was slightly elevated indicating
      polarisation towards a regulatory T cell phenotype. These results provide further
      supportive evidence to justify the clinical evaluation of BM for managing
      diseases involving chronic systemic and brain inflammation driven by the innate
      immune system. 

PMID- 24452711
TI  - Matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo
      cells by inactivating Akt pathway.
AB  - The present study has investigated the anti-tumor activity and the underlying
      mechanisms of matrine on human colon cancer LoVo cells. Matrine inhibited the
      proliferation of the cells in dose- and time-dependent manners. The concentration
      required for 50 % inhibition (IC50) was 1.15, 0.738, and 0.414 mg/ml, when cell
      were incubated with matrine for 24, 48, and 72 h, respectively. Matrine induced
      cell cycle arrest at G1 phase by downregulating cyclin D1 and upregulating p27
      and p21. Matrine induced cell apoptosis by reducing the ratio of Bcl-2/Bax and
      increasing the activation of caspase-9 in a dose-dependent manner. Matrine
      displayed its anti-tumor activity by inactivating Akt, the upstream factor of the
      above proteins. Matrine significantly reduced the protein levels of pAkt, and
      increased the protein levels of other downstream factors, pBad and pGSK-3beta.
      Specific inhibition of pAkt induced cell apoptosis, and synergized with matrine
      to inhibit the proliferation of LoVo cells; whereas activation of Akt neutralized
      the inhibitory effect of matrine on cell proliferation. The present study has
      demonstrated that matrine inhibits proliferation and induces apoptosis of human
      colon cancer LoVo cells by inactivating Akt pathway, indicating matrine may be a
      potential anti-cancer agent for colon cancer.

PMID- 24452712
TI  - Reference gene selection for qRT-PCR in Caragana korshinskii Kom. under different
      stress conditions.
AB  - Caragana korshinskii Kom., which is widely distributed in the northwest China and
      Mongolia, is an important forage bush belonging to the legume family with high
      economic and ecological value. Strong tolerance ability to various stresses makes
      C. korshinskii Kom. a valuable species for plant stress research. In this study,
      suitable reference genes for quantitative real-time reverse transcription PCR
      (qRT-PCR) were screened from 11 candidate reference genes, including ACT, GAPDH,
      EF1alpha, UBQ, TUA, CAP, TUB, TUB3, SKIP1, SKIP5-1 and SKIP5-2. A total of 129
      samples under drought, heat, cold, salt, ABA and high pH treatment were profiled,
      and software such as geNORM, NormFinder and BestKeeper were used for reference
      gene evaluation and selection. Different suitable reference genes were selected
      under different stresses. Across all 129 samples, GAPDH, EF1alpha and SKIP5-1
      were found to be the most stable reference genes, and EF1alpha+SKIP5-1 is the
      most stable reference gene combination. Conversely, TUA, TUB and SKIP1 were not
      suitable for using as reference genes owing to their great expression variation
      under some stress conditions. The relative expression levels of CkWRKY1 were
      detected using the stable and unstable reference genes and their applicability
      was confirmed. These results provide some stable reference genes and reference
      gene combinations for qRT-PCR under different stresses in C. korshinskii Kom. for
      future research work, and indicate that CkWRKY1 plays essential roles in response
      to stresses in C. korshinskii.

PMID- 24452713
TI  - Atorvastatin inhibits hyperglycemia-induced expression of osteopontin in the
      diabetic rat kidney via the p38 MAPK pathway.
AB  - Osteopontin (OPN), a large phosphoglycoprotein adhesion molecule, which is up
      regulated in the kidneys of humans and mice with diabetes, has emerged as a
      potentially key pathophysiological contributor in diabetic nephropathy. Here, we
      investigated the role of OPN in kidney injury caused by diabetic nephropathy and
      the effect of atorvastatin on the expression of OPN and on diabetic nephropathy.
      Diabetes was induced with streptozotocin in rats, and atorvastatin (5 mg/kg) was
      orally administered once a day for 8 weeks. We analyzed the expression and
      regulation of OPN in the kidneys of streptozotocin-induced diabetic Sprague
      Dawley albino rats by immunohistochemistry and western blot analysis. The
      expression of OPN was increased in diabetic rat kidney, and atorvastatin
      inhibited this process. Atorvastatin also decreased the expression and
      phosphorylation of p38. In vitro, atorvastatin inhibited the high glucose-induced
      OPN expression in Madin-Darby canine kidney epithelial cells through the p38 MAPK
      signaling pathway. These results suggested that atorvastatin reduced the
      expression of OPN through inhibition of the p38 MAPK pathway. The expression of
      OPN was associated with kidney injury. These molecules may represent therapeutic
      targets for the prevention of acute kidney injury induced by diabetes.

PMID- 24452714
TI  - Genetic variation in RPOIILS gene encoding RNA polymerase II largest subunit from
      Leishmania major.
AB  - Leishmaniasis is a geographically widespread severe disease which includes
      visceral leishmaniasis, cutaneous leishmaniasis (CL). There are 350 million
      people at risk in over 80 countries. In the Old World, CL is usually caused by
      Leishmania major, Leishmania tropica, and Leishmania aethiopica complex which 90
      % of cases occurring in Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, Syria,
      Brazil, and Peru. Recently, some reports showed that some strains of L. major
      have internal transcribed space (ITS-1) with differential size exhibiting
      homology with the related gene in a divergent genus of kinetoplastida, the
      Crithidia. This prompted us to analyze the mentioned gene in 100 isolates
      obtained from patients with suspected CL. After obtaining samples from 100
      patients, DNA extraction was performed and ITS-1 was analyzed using PCR-RFLP.
      These samples were sequenced for verifying their homology. Then, RPOIILS gene was
      analyzed in the samples that their ITS-1 gene exhibiting homology with the
      related gene in Crithidia. Results showed that 10 % of the isolates have ITS-1
      exhibiting different size with the routine ones. Sequencing of them showed their
      similarity to the one from Crithidia fasciculata. RPOIILS gene encoding RNA
      polymerase II largest subunit analysis showed genetic diversity. This study might
      also help in solving the problems concerning Leishmaniasis outbreak currently
      facing in Iran and some other endemic regions of the world.

PMID- 24452716
TI  - Genetic variations and head and neck cancer risks.
AB  - Variations in CYP1A1, GSTM1, GSTT1 and GSTP1 in head and neck cancer have been
      frequently found in literature. But these studies give an overview of these
      genetic variations in different populations. The current mini review focus on the
      analysis of these genetic variations at DNA, mRNA and protein levels in the same
      study group. Eight publications were reviewed on the same study samples yielding
      results at DNA, mRNA and protein levels. At DNA level, CYP1A1 showed
      significantly higher mutations in head and neck cancer patients compared to
      controls at g.2842A>C and g.2842_2843insT. GSTM1 and GSTT1 showed deletion
      polymorphisms and heterozygous deletion confers protection against cancer.
      Mutations were also found in GSTP1 at g.2848A>T, g.2849G>A, g.1074delC and
      g.1466delC. mRNA and protein expressional analysis revealed underexpression of
      CYP1A1, loss or underexpression of GSTM1 and GSTT1 and overexpression of GSTP1.
      In addition an unusual intronic variant of GSTP1 mRNA was also found, retaining
      the intronic portion between exons. The current review gives a complete study
      overview regarding CYP1A1, GSTM1, GSTT1 and GSTP1 variations at DNA, mRNA and
      protein levels in head and neck cancer. The review is helpful in designing a new
      experiment or gene therapy for head and neck cancer patients.

PMID- 24452715
TI  - Cloning and molecular modelling of pectin degrading glycosyl hydrolase of family
      28 from soil metagenomic library.
AB  - Western Ghats of India is recognized as one of the 12 mega diversity regions of
      the world and is the hot spot for unrevealed microbial diversity. To explore the
      diversity of polysaccharide degrading enzymes in that region, metagenomic library
      was constructed from forest soil of Southern Western Ghats region. Nine
      pectinolytic clones with the ability to degrade citrus pectin were isolated based
      on function based screening of the library. Sequence analysis of pg_4 clone
      containing revealed that it contained GH family 28 domain (pfam00295) belonging
      to polygalacturonase superfamily (PLN03003). Its amino acid sequence analysis
      showed 25-55 % identity to the other well-characterized polygalacturonases.
      Molecular modeling of pg_4 revealed that it comprised of three right handed
      parallel beta sheets, one anti-parallel beta sheet and one alpha helix with three
      conserved catalytic residue D 2263, D 284-85 and H 312 at the C terminal end. The
      enzyme characterized was able to hydrolyze both apple and citrus pectin with K m
      values of 1.685 and 1.542 mg ml(-1) and retained more that 80 % of activity at pH
      5-9 and temperature 20-60  degrees C.

PMID- 24452717
TI  - MicroRNA-30c serves as an independent biochemical recurrence predictor and
      potential tumor suppressor for prostate cancer.
AB  - MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various
      human malignancies. However, the involvement of miR-30c in prostate cancer (PCa)
      is still unclear. The aim of this study was to investigate the molecular function
      and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in
      PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR).
      Additionally, the associations of miR-30c expression with clinicopathological
      features and prognosis in PCa patients were analyzed. The potential role of miR
      30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays.
      MiR-30c was significantly down-regulated in PCa tissues and cells compared with
      the corresponding controls (P<0.05). In addition, the downregulation of miR-30c
      in PCa tissues was significantly associated with higher Gleason score (P=0.009),
      advanced pathological stage (P=0.016) and biochemical recurrence (P=0.034).
      Moreover, Kaplan-Meier survival analysis showed that the reduced expression of
      miR-30c was correlated with shorter biochemical recurrence-free survival
      (P=0.023). The multivariate analysis also identified miR-30c as an independent
      prognostic predictor for biochemical recurrence-free survival in patients with
      PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation,
      migration and invasion of PCa cells in vitro. Our data indicated the involvement
      of miR-30c in PCa progression and suggested its potential role as an independent
      predictor of biochemical recurrence in PCa. On cellular level, miR-30c may
      function as a tumor suppressor for PCa cells by inhibiting tumor cell
      proliferation, migration and invasion.

PMID- 24452718
TI  - Meta-analysis of the association between common interleukin-1 polymorphisms and
      dental implant failure.
AB  - Interleukin-1 (IL) plays a pivotal role in immune-inflammatory response that
      maintains periodontal homeostasis. A number of epidemiological studies have been
      conducted to investigate the associations between common polymorphisms of IL-1
      (IL-1A, IL-1B) genes and risk of peri-implant disease, but the findings remain
      inconclusive. Thirteen studies evaluating the association between IL-1
      polymorphisms and risk for peri-implant diseases (implant failure/loss, peri
      implantitis) were included. Fixed model or random-effects models were applied to
      calculate overall and ethnicity-specific summary odds ratios (ORs) and
      corresponding 95% confidence intervals (CIs) as risk estimates for IL-1
      polymorphisms individually or in combination. Heterogeneity and publication bias
      were evaluated by Q-test, I2 statistic, Begg's funnel plot and Egger's test
      accordingly. The composite genotype of IL-1A (-889) and IL-1B (+3954) was
      associated with increased risk of implant failure/loss (OR 1.76, 95% CI 1.21
      2.57) and peri-implantitis (OR 2.34, 95% CI 1.03-5.33). The significance was
      borderline in European descents (implant failure/loss: OR 1.48, 95% CI 0.99-2.22;
      peri-implantitis: OR 1.65, 95% CI 1.00-2.73). T allele of IL-1B (-511) was
      associated with increased risk of implant failure/loss (OR 1.28, 95% CI 1.01
      1.62), while the association was not significant in European descents (OR 1.12,
      95% CI 0.85-1.48). These findings support a potential role of IL-1 polymorphisms,
      particularly the composite genotype of IL-1A (-889) and IL-1B (+3954), in peri
      implant disease susceptibility. More studies with large sample size are needed to
      validate the associations.

PMID- 24452719
TI  - A novel genotyping method for detection of the CRHR1 (rs1396862: C>T) gene
      variation among North Indian population.
AB  - Today, the genomic revolution in epidemiology, medicine and population based
      genetic association studies are results of on-going refocusing efforts toward
      development of inexpensive and accurate techniques for SNP genotyping. Despite
      this considerable gain, high throughput and routinely applicable newer SNP
      detection techniques are still needed. Therefore, aim of this study was to
      develop and validate a simple, rapid and inexpensive restriction enzyme based
      method for genotyping of corticotrophin-releasing hormone receptor1 (CRHR1;
      rs1396862: C>T) gene variant. This polymorphism has been investigated in a
      variety of psychiatric and association studies of asthma. A total of 250 healthy
      volunteers were recruited from same ethnicity and their blood DNA samples were
      employed for genotyping. Primers were designed using Batch primer3 Software.
      Specificity and functionality of primers were tested with BLAST database and UCSC
      In-silco PCR respectively. The lake of a PstI recognition site was seen with T
      allele. The allele frequencies for rs1396862: C>T were 0.88 (C allele) and 0.12
      (T allele). We get 100% concordant genotyping results for sequencing and PCR
      RFLP. This newer genotyping approach lowers the cost and increased the speed. It
      is particularly useful for small basic research studies of complex genetic
      disorder.

PMID- 24452720
TI  - Microsatellite instability typing in serum and tissue of patients with colorectal
      cancer: comparing real time PCR with hybridization probe and high-performance
      liquid chromatography.
AB  - Allelic variation of BAT-25 (a 25-repeat quasimonomorphic poly T) and BAT-26 (a
      26-repeat quasimonomorphic polyA) loci as two mononucleotide microsatellite
      markers, were analyzed with high-performance liquid chromatography (HPLC)
      compared with Real-Time PCR using hybridization probes. BAT-26 and BAT-25 markers
      were used to determine an appropriate screening technique with high sensitivity
      and specificity to diagnose microsatellite instability (MSI) status in patients
      with colorectal cancer (CRC). One of the pathways in colorectal tumor genesis is
      microsatellite instability (MSI+). MSI is detected in about 15% of all CRCs; 3%
      are of these are associated with Lynch syndrome and the other 12% are caused by
      sporadic. Colorectal tumors with MSI have distinctive features compared with
      microsatellite stable tumors. Due to the high percentage of MSI+ CRC in Iran,
      screening of this type of CRC is imperative. Two markers were analyzed in tissues
      and sera of 44 normal volunteers and tumor and matched normal mucosal tissues as
      well as sera of 44 patients with sporadic CRC. The sensitivity and specificity of
      BAT-26 with real time PCR method (Hybridization probe) were 100% in comparison
      with sequencing method as the gold standard, while HPLC had a lower sensitivity
      and specificity. According to HPLC data, BAT-26 was more sensitive than BAT-25 in
      identifying MSI tumors. Therefore, MSI typing using the BAT-26 hybridization
      probe method compared to HPLC could be considered as an accurate method for
      diagnosing MSI in CRC tumors but not in serum circulating DNAs.

PMID- 24452721
TI  - The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal
      aortic aneurysm.
AB  - The most important feature of abdominal aortic aneurysm (AAA) pathogenesis is an
      enzymatic degradation of elastic lamellae and extracellular matrix proteins
      particularly with participation of matrix metalloproteinases. Plasmin, which is
      responsible for the dissolution of fibrin in blood vessels, plays also a key role
      in the cascade for activation of the metalloproteinases. The purpose of this
      study was to evaluate the influence of selected polymorphisms in genes coding for
      tissue plasminogen activator (-7351 C/T polymorphism), urokinase-type plasminogen
      activator (1788 C/T polymorphism) and plasminogen activator inhibitor 1 (-675
      4G/5G and -844 G/A polymorphism) on the susceptibility to AAA. We performed a
      case-control study of 153 polish patients hospitalized due to AAA and compared
      them with matched healthy control subjects. The polymorphisms were ascertained
      through genotyping by polymerase chain reaction and restriction digestion of
      amplified fragments or through high-resolution melting analysis. In this study we
      have found lower frequency of wild-type GG genotype of the -844G/A PAI-1
      polymorphism in cases than in controls, what may suggest the protective effect of
      this genotype for the risk of AAA development. None of the remaining
      polymorphisms tested were associated with AAA occurrence. 

PMID- 24452722
TI  - In vitro analysis of splice site mutations in the CLCN1 gene using the minigene
      assay.
AB  - Mutations in the chloride channel gene CLCN1 cause the allelic disorders Thomsen
      (dominant) and Becker (recessive) myotonia congenita (MC). The encoded protein,
      ClC-1, is the primary channel that mediates chloride (Cl-) conductance in
      skeletal muscle. Mutations in CLCN1 lower the channel's threshold voltage,
      leading to spontaneous action potentials that are not coupled to neuromuscular
      transmission and resulting in myotonia. Over 120 mutations in CLCN1 have been
      described, 10% of which are splicing defects. Biological specimens suitable for
      RNA extraction are not always available, but obtaining genomic DNA for analysis
      is easy and non-invasive. This is the first study to evaluate the pathogenic
      potential of novel splicing mutations using the minigene approach, which is based
      on genomic DNA analysis. Splicing mutations accounted for 23% of all pathogenic
      variants in our cohort of MC patients. Four were heterozygous mutations in four
      unrelated individuals, belonging to this cohort: c.563G>T in exon 5; c.1169-5T>G
      in intron 10; c.1251+1G>A in intron 11, and c.1931-2A>G in intron 16. These
      variants were expressed in HEK 293 cells, and aberrant splicing was verified by
      in vitro transcription and sequencing of the cDNA. Our findings confirm the need
      to further investigate the nature of rearrangements associated with this class of
      mutations and their effects on mature transcripts. In particular, splicing
      mutations predicted to generate in-frame transcripts may generate out-of-frame
      mRNA transcripts that do not produce functional ClC-1. Clinically, incomplete
      molecular evaluation could lead to delayed or faulty diagnosis.

PMID- 24452723
TI  - Molecular characterization, expression profile, and polymorphism of goose
      dopamine D1 receptor gene.
AB  - Dopamine D1 receptor (DRD1) is one of the dopamine receptors with seven
      transmembrane domains that are coupled to the G protein. In the present study, we
      cloned the full coding region of DRD1 gene by the reverse transcription
      polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends from the
      goose hypothalamus tissues. Results showed that the goose DRD1 cDNA (GenBank:
      KF156790) contained a 1,356 bp open reading frame encoding a protein 452 amino
      acid with a molecular weight of 50.52 kDa and a isoelectric point of 6.96.
      Bioinformatics analysis indicated that the deduced amino acid sequence was 71-98%
      identical to the DRD1 protein of other species, contained seven transmembrane
      domains and four N-glycosylation sites. A phylogenetic tree analysis revealed
      that the deduced goose DRD1 protein had a close genetic relationship and
      evolutional distance with that of duck, chicken, and zebra finch. The semi
      quantitative RT-PCR analysis displayed goose DRD1 gene was widely expressed in
      all detected tissues, including heart, lung, liver, spleen, kidney, breast
      muscle, duodenum, sebum, pituitary, hypothalamus, ovary and oviduct. Eighteen
      single nucleotide polymorphisms were indentified in 3,169 bp length of this gene.
      For G90A mutation, the genotyping analysis of PCR-TspRI-RFLP showed the allele G
      was in dominance in all detected goose breeds, and the allele frequencies of this
      polymorphism were significantly different between Chinese goose breeds and
      foreign breeds (P<0.01). These findings will help us understand the functions of
      the DRD1 gene and the molecular breeding in geese.

PMID- 24452724
TI  - Risky alcohol use among migrant women in entertainment venues in China.
AB  - AIMS: The aims of this study are to describe the prevalence of hazardous drinking
      among migrant women working in entertainment venues in an urban setting in China
      and to identify specific risk factors and locations where hazardous drinking
      occurs. METHODS: From March to July 2012, we conducted a cross-sectional survey
      of 358 young migrant women working in entertainment venues in the capital city of
      Hefei, Anhui Province, China. Participants were asked about information regarding
      their demographic characteristics, sexual behavior, mental health, alcohol use
      and drug use. RESULTS: Overall, 203 (57%) participants had an AUDIT score >=8
      (risky drinking) and 95 (27%) women had an AUDIT >=16 (probable dependence).
      Greater likelihood of probable alcohol dependence was associated with being
      younger (OR = 0.85, 95% CI: 0.76-0.95), working at an affluent venue (OR = 2.46,
      95% CI: 1.13-5.36) and depressive symptoms during the past week (OR = 2.74, 95%
      CI = 1.10-6.83). CONCLUSION: Our study documents risky drinking practices among
      female migrants, irrespective of whether or not women reported engaging in
      commercial sex, working in entertainment venues. Our data suggest that
      entertainment venues, particularly those that are higher end (i.e. affluent)
      venues, should be targeted for public health interventions aimed to reduce
      harmful drinking practices.

PMID- 24452725
TI  - First evidence of putrescine involvement in mitigating the floral malformation in
      mangoes: a scanning electron microscope study.
AB  - Floral malformation is the most destructive disease in mangoes. To date, the
      etiology of this disease has not been resolved. There are indications that stress
      stimulated ethylene production might be responsible for the disease. Putrescine
      mediates various physiological processes for normal functioning and cellular
      metabolism. Here, the effect of putrescine in concentration ranging from 10(-1)
      to 10(-3) M was evaluated on disease incidence during mango flowering seasons of
      2012 and 2013. In a scanning electron microscopy (SEM) study, putrescine (10(-2)
      M)-treated malformed floral buds bloomed into opened flowers with separated
      sepals and/or petals like healthy, whereas the untreated (control) malformed buds
      remained deformed. Further, malformed flowers recovered upon putrescine
      treatment, displaying clearly bilobed anthers, enclosing a large number of normal
      pollen grains and functional ovary with broad stigmatic surface as compared to
      control. The present findings provide the first report to demonstrate the role of
      putrescine in reducing various adverse effects of stress ethylene via
      decelerating the higher pace of its biosynthesis. It stabilizes the normal
      morphology, development, and functions of malformed reproductive organs to
      facilitate successful pollination, fertilization, and, thereby, fruit set in
      mango flowers. However, putrescine-ethylene-mediated cell signaling network,
      involving various genes to trigger the response, which regulates a wide range of
      developmental and physiological processes leading to normal cell physiology,
      needs to be investigated further. 

PMID- 24452727
TI  - Clinical implications and correlates of Q waves in patients with ST-elevation
      myocardial infarction treated with fibrinolysis: observations from the CLARITY
      TIMI 28 trial.
AB  - BACKGROUND: The relationships between Q waves that appear during the acute phase
      of ST-elevation myocardial infarction (STEMI), clinical characteristics, ST
      segment resolution (STRes), and clopidogrel therapy in patients treated with
      fibrinolysis are not well described. HYPOTHESIS: We hypothesized that Q waves
      would be associated with less successful reperfusion and increased cardiovascular
      events. METHODS: In the CLARITY-TIMI 28 trial, 3491 STEMI patients treated with
      fibrinolysis were randomized to clopidogrel or placebo. Electrocardiograms were
      evaluated for STRes post-fibrinolysis and the presence of pathologic Q waves
      during the index hospitalization in 3322 patients. RESULTS: Q waves were
      identified in 2045 patients (61.6%) prior to discharge and were associated with
      increased odds of congestive heart failure (CHF) (adjusted odds ratio [ORadj ]:
      2.10, P = 0.002) or the composite of cardiovascular death/CHF at 30 days (ORadj :
      2.08, P <= 0.001). Q waves were associated with lower odds of Thrombolysis in
      Myocardial Infarction [TIMI] flow grade 2 to 3 (ORadj : 0.78, P = 0.028), TIMI
      myocardial perfusion grade 3 (ORadj : 0.83, P = 0.029), and complete STRes at 90
      minutes (ORadj : 0.80, P = 0.030). Patients with both a Q wave and incomplete
      STRes 90 minutes after fibrinolysis were at higher risk for cardiovascular death
      or CHF (11.1%) than patients with no Q wave and at least partial STRes (1.9%).
      Overall, clopidogrel tended to be equally or more effective in patients without Q
      waves compared to those with Q waves. CONCLUSIONS: Among STEMI patients treated
      with fibrinolysis, evaluating for Q waves prior to discharge is a simple method
      of assessing for less successful reperfusion and an increased risk of adverse 30
      day cardiovascular outcomes. The combination of Q waves and 90-minute STRes
      allows additional risk refinement.

PMID- 24452726
TI  - Prospective, unmasked evaluation of the iStent(r) inject system for open-angle
      glaucoma: synergy trial.
AB  - INTRODUCTION: Micro-invasive glaucoma surgical implantation of trabecular micro
      bypass stents, previously shown to be safe and effective for open-angle glaucoma
      (OAG) subjects during cataract surgery, was considered for evaluation as a sole
      procedure. The aim of this study was to evaluate the safety and intraocular
      pressure (IOP)-lowering efficacy after ab interno implantation of two Glaukos
      Trabecular Micro-Bypass iStent inject second generation devices in subjects with
      OAG. This study was performed at sites in France, Germany, Italy, Republic of
      Armenia, and Spain. METHODS: In this pan-European, multi-center prospective, post
      market, unmasked study, 99 patients with OAG on at least two topical ocular
      hypotensive medications who required additional IOP lowering to control glaucoma
      disease underwent implantation of two GTS400 stents in a stand-alone procedure.
      Patients were qualified if they presented with preoperative mean IOP between 22
      and 38 mmHg after medication washout. Postoperatively, subjects were assessed at
      Day 1, Months 1, 3, 6, 7, 9, and 12. IOP, medication use and safety were assessed
      at each visit. RESULTS: Sixty-six percent of subjects achieved IOP <=18 mmHg at
      12 months without medication, and 81% of subjects achieved Month 12 IOP <= 18
      mmHg with either a single medication or no medication. Mean baseline washout IOP
      values decreased by 10.2 mmHg or 39.7% from 26.3 (SD 3.5) mmHg to 15.7 (SD 3.7)
      mmHg at Month 12. Mean IOP at 12 months was 14.7 (SD 3.1) mmHg in subjects not
      using ocular hypotensive medications. Reduction from preoperative medication
      burden was achieved in 86.9% of patients, including 15.2% with reduction of one
      medication and 71.7% with reduction of two or more medications. Postoperative
      complications occurred at a low rate and resolved without persistent effects.
      CONCLUSION: In this series, implantation of two trabecular micro-bypass second
      generation stents in subjects with OAG resulted in IOP and medication reduction
      and favorable safety outcomes.

PMID- 24452728
TI  - Prevalence and extent of atherosclerotic coronary artery disease and related
      outcome based on coronary computed tomographic angiography in asymptomatic
      elderly patients: retrospective cohort study.
AB  - There is little data regarding coronary artery disease (CAD) and/or
      atherosclerotic plaques on coronary computed tomographic angiography (CCTA) among
      the elderly and its outcome, especially in asymptomatic patients. Using CCTA, we
      evaluated the prevalence and extent of CAD and/or atherosclerosis and related
      outcomes in asymptomatic elderly patients as compared with symptomatic elderly
      patients. The study included 1,196 consecutive patients aged 70 years or older
      who underwent CCTA over a 2-year period. Data were retrospectively evaluated for
      clinical cardiovascular risk factors with co-morbidities, and CCTA findings,
      including calcium scores, atherosclerotic plaques (number, plaque-segment score,
      plaque-extent score, and plaque-significant score) and presence of significant
      CAD. Follow-up data for active management and all-cause mortality after CCTA were
      collected for 2 years. Two-sided Student's t test for independent samples, Chi
      square contingency tables, and Kaplan-Meier survival curves were used for
      statistical analysis. Data for 454 asymptomatic and 742 symptomatic elderly
      patients were analyzed. The prevalence of significant CAD and the extent of
      atherosclerotic plaques did not differ between the two groups (all P > 0.05).
      Asymptomatic patients with significant CAD on CCTA, were less likely to receive
      active management (P < 0.001), which may be related to the higher death rate in
      this group (P = 0.012) than in the symptomatic patients with significant CAD.
      Overall, symptoms were not related to the presence of significant CAD or to the
      extent of atherosclerosis in these elderly patients. However, all-cause mortality
      was higher in the asymptomatic patients with significant CAD than in the
      symptomatic ones.

PMID- 24452729
TI  - Randomized comparison of biolimus-eluting stents with biodegradable polymer
      versus everolimus-eluting stents with permanent polymer coatings assessed by
      optical coherence tomography.
AB  - We sought to compare the healing patterns of biolimus-eluting stents with
      biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with
      permanent polymer (PP-EES, Xience) using intravascular optical coherence
      tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary
      lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19).
      Stent tissue coverage and apposition as well as the incidence of peri-strut low
      intensity area (PLIA) were assessed by OCT at 6-8 months. Generalized linear
      mixed models were used to account for clustered data. OCT imaging was available
      for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890
      struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of
      uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63-3.79), P =
      0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21-12.5], P =
      0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %)
      had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was
      similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43
      2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar
      stent coverage and apposition as assessed by OCT at 6-8 months. In addition, PLIA
      possible markers of delayed arterial healing-were observed with similar frequency
      in both groups.

PMID- 24452730
TI  - Factors associated with high transmission risk and detectable plasma HIV RNA in
      HIV-infected MSM on ART.
AB  - Summary HIV transmission risk is increased during antiretroviral therapy (ART)
      use if individuals are not virologically suppressed and engage in high risk
      transmission behaviour. Baseline data of HIV-infected men who have sex with men
      (MSM) with recent history of risky behaviour on ART for >=3 months (n = 139) were
      evaluated to assess predictors of detectable viraemia and HIV transmission risk
      taking behaviour. Twenty-four subjects had viral load (VL) >75 copies/mL and 12
      had VL >1000 copies/mL. In multivariable regression analyses, subjects with VL
      >75 copies/mL were more likely to be Black (OR = 4.48, p = 0.007), have lower CD4
      cell counts (OR = 0.727, p = 0.005) and have used methamphetamines in the last
      month (OR = 6.64, p = 0.019). Subjects with VL >1000 copies/mL were more likely
      to have lower CD4 cell counts (OR = 0.494, p = 0.004), report <90% adherence (OR
      = 7.94; p = 0.046) and have used methamphetamines in the last month (OR = 10.01,
      p = 0.034). Subjects with VL >75 copies/mL with the greatest transmission risk
      behaviour (n = 14) were more likely to be Black (OR = 8.00, p = 0.006), have
      lower CD4 cell counts (OR = 0.657, p = 0.009) and have used methamphetamines in
      the last month (OR = 5.20, p = 0.042). High risk HIV transmission behaviour with
      viraemia occurred in 10% of the cohort. Future efforts to reduce HIV transmission
      among MSM on ART will require combined interventions that target risk-taking
      behaviours and substance use. 

PMID- 24452731
TI  - Durability of response to vaccination against viral hepatitis A in HIV-infected
      patients: a 5-year observation.
AB  - The aim of this study was to estimate the prevalence of total antibodies to
      hepatitis A virus (anti-HAV-T) in the group of HIV-positive adults in Lodz region
      of Poland, and to evaluate the response and long-term immunity after vaccination
      against hepatitis A virus. In the group of 234 HIV-infected patients, 72 persons
      (30.8%) were anti-HAV-T positive (>20 IU/L). In multivariate analysis, two
      independent factors associated with the presence of anti-HAV-T were identified:
      the age of patients (OR = 1.07) and the presence of antibodies to hepatitis C
      virus (OR = 2.87). Vaccination was completed in 83 patients. Good response (anti
      HAV-T >20 IU/L one month after the booster dose) was obtained in 79.5% of
      patients. In patients with CD4 >200 cells/uL in multivariate analysis only
      presence of antibodies to hepatitis C virus was a prognostic factor for the
      response to vaccination (OR = 0.13). Among responders available for the follow
      up, 82% (50 out of 61) had detectable anti-HAV-T at 1 year and 75.5% (37 out of
      49) at 5 years. Our results demonstrate that most of the studied HIV-positive
      patients were susceptible to hepatitis A virus infection. Most HIV-infected
      adults with high CD4 counts had a durable response even up to 5 years after
      vaccination. Patients with a HIV/hepatitis C virus coinfection displayed a worse
      response to vaccination. 

PMID- 24452732
TI  - Black stone - a natural remedy for premature ejaculation and performance
      enhancement, or maybe not?
AB  - We describe the use of a non-prescribed aid (Black stone) for premature
      ejaculation that resulted in a chemical burn on the penis with an appearance
      similar to severe balanitis. 

PMID- 24452733
TI  - Correlates of syphilis seropositivity and risk for syphilis-associated adverse
      pregnancy outcomes among women attending antenatal care clinics in the Democratic
      Republic of Congo.
AB  - Screening and treatment for syphilis among pregnant women is the primary means of
      prevention of congenital syphilis. Sentinel surveillance for syphilis can inform
      these prevention efforts. We reviewed antenatal syphilis screening results to
      assess trends and to identify correlates of seropositivity among women attending
      antenatal care clinics in the Democratic Republic of Congo during 2011. Syphilis
      seropositivity among the 17,669 women attending the antenatal care clinics during
      2011 was 4.2% (range 0.4%-16.9%). Syphilis seropositivity was significantly
      higher among women attending rural clinics (5.0%) as compared to urban clinics
      (3.0%) and those tested in antenatal care clinics in the provinces of Equateur
      (7.6%) and Orientale (7.7%) as compared to other provinces (p < 0.001). Based on
      the antenatal care syphilis seroprevalence and national pregnancy estimates, we
      estimate that approximately 128,591 pregnant women countrywide would have tested
      seropositive for syphilis during 2011. Over 85,000 adverse pregnancy outcomes
      would have resulted from these maternal infections, assuming prenatal syphilis
      diagnosis and treatment were not available. The prevalence of syphilis was
      highest in rural areas, but exceeded 1% in every area, indicating a need to
      assure screening and treatment throughout Democratic Republic of Congo. These
      sentinel surveillance estimates can be used to guide national congenital syphilis
      prevention efforts.

PMID- 24452734
TI  - HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the
      metastatic colonization of cancers in lungs.
AB  - Hypoxia-inducible factor 1 (HIF-1) has been associated with distant tumor
      metastasis; however, its function in multiple metastatic processes has not yet
      been fully elucidated. In the present study, we demonstrated that cancer cells
      transiently upregulated HIF-1 activity during their metastatic colonization after
      extravasation in the lungs in hypoxia-independent and reactive oxygen species
      (ROS)-dependent manners. Transient activation induced the expression of lactate
      dehydrogenase A and phosphorylation of the E1alpha subunit of pyruvate
      dehydrogenase, which indicated the reprogramming of glucose metabolic pathways
      from mitochondrial oxidative phosphorylation to anaerobic glycolysis and lactic
      acid fermentation. The administration of the HIF-1 inhibitor, YC-1, inhibited
      this reprogramming, increased intratumoral ROS levels, and eventually suppressed
      the formation of metastatic lung tumors. These results indicate that HIF-1
      mediated metabolic reprogramming is responsible for the survival of metastatic
      cancers during their colonization in lungs by reducing cytotoxic ROS levels;
      therefore, its blockade by HIF-1-inhibitors is a rational strategy to prevent
      tumor metastasis. 

PMID- 24452735
TI  - A novel thromboxane A2 receptor N42S variant results in reduced surface
      expression and platelet dysfunction.
AB  - A small number of thromboxane receptor variants have been described in patients
      with a bleeding history that result in platelet dysfunction. We have identified a
      patient with a history of significant bleeding, who expresses a novel
      heterozygous thromboxane receptor variant that predicts an asparagine to serine
      substitution (N42S). This asparagine is conserved across all class A GPCRs,
      suggesting a vital role for receptor structure and function.We investigated the
      functional consequences of the TP receptor heterozygous N42S substitution by
      performing platelet function studies on platelet-rich plasma taken from the
      patient and healthy controls. We investigated the N42S mutation by expressing the
      wild-type (WT) and mutant receptor in human embryonic kidney (HEK) cells.
      Aggregation studies showed an ablation of arachidonic acid responses in the
      patient, whilst there was right-ward shift of the U46619 concentration response
      curve (CRC). Thromboxane generation was unaffected. Calcium mobilisation studies
      in cells lines showed a rightward shift of the U46619 CRC in N42S-expressing
      cells compared to WT. Radioligand binding studies revealed a reduction in BMax in
      platelets taken from the patient and in N42S-expressing cells, whilst cell
      studies confirmed poor surface expression. We have identified a novel thromboxane
      receptor variant, N42S, which results in platelet dysfunction due to reduced
      surface expression. It is associated with a significant bleeding history in the
      patient in whom it was identified. This is the first description of a naturally
      occurring variant that results in the substitution of this highly conserved
      residue and confirms the importance of this residue for correct GPCR function. 

PMID- 24452736
TI  - Preoperative hepatic CT perfusion as an early predictor for the recurrence of
      esophageal squamous cell carcinoma: initial clinical results.
AB  - Reports suggest that hepatic blood flow may have an association with cancer
      progression. The aim of the present study was to evaluate whether the hepatic
      blood flow measured by CT perfusion (CTP) may identify patients at high-risk for
      postoperative recurrence of esophageal squamous cell carcinoma (ESCC). Prior to
      surgery, hepatic CTP images were obtained using a 320-row area detector CT. The
      data were analyzed by a commercially available software based on the dual input
      maximum slope method, and arterial blood flow (AF, ml/min/100 ml tissue), portal
      blood flow (PF, ml/min/100 ml tissue) and perfusion index [PI (%) = AF/AF + PF x
      100] were measured. These parameters were compared with the pathological stage
      and outcome of the ESCC patients. Forty-five patients with ESCC were eligible for
      this study. The median follow-up period was 17 months, and recurrences were
      observed in 9 patients (20%). The preoperative PI values of the 9 patients with
      recurrence were significantly higher than those of the 36 patients without
      recurrence (23.9 vs. 15.9, P=0.0022). Patients were categorized into the
      following two groups; high PI (>20) and low PI (<20). The recurrence-free
      survival of the low PI group was significantly better than that of the high PI
      group (P<0.0001). A multivariate analysis showed that a high PI was an
      independent risk factor for recurrence (odds ratio, 19.1; P=0.0369).Therefore,
      the preoperative PI of the liver may be a useful imaging biomarker for predicting
      the recurrence of patients with esophageal cancer.

PMID- 24452737
TI  - Association between fragile X premutation and premature ovarian failure: a case
      control study and meta-analysis.
AB  - AIM: The aim of the present study was to investigate the association between FMR1
      premutation and premature ovarian failure (POF) patients in Indian population,
      and a meta-analysis of published results was undertaken to clarify whether FMR1
      premutation consistently contributed to the susceptibility. METHODS: A total of
      289 POF samples and 360 control samples were included in the study. Repeat
      variation was checked using GeneScan technique. Results were analyzed with
      GeneMapper software. Meta-analysis was performed using the Open Meta-Analyst and
      STATA 12.0 software. The crude odds ratio with 95 % confidence interval (CI) was
      computed to assess the strength of the associations. RESULTS: The assayed case
      and control population showed 29 different CGG repeat sizes (alleles), ranging
      from 7 to 40. Within this population, we found that the CGG repeat length
      polymorphisms were within the normal range of 6-55 in both patients as well as
      control samples. Eleven case-control studies were included in the meta-analysis
      with a total of 1,313 POF cases and 3,132 control subjects. Our meta-analysis
      revealed that there was a significant difference in the incidence of FMR1
      premutation between POF cases and control subjects with p value <0.001 (OR 5.41;
      95 % CI 2.53, 11.61). CONCLUSIONS: We found no significant association between
      FMR1 CGG repeat premutation and POF in Indian population. However, the meta
      analysis showed an increased risk of POF associated with a premutation,
      especially among populations from European descent. Further functional research
      should be performed to explain the inconsistent results in different ethnicities
      and POF susceptibility.

PMID- 24452738
TI  - Estimating risk factors for spontaneous preterm delivery in teen pregnancies.
AB  - PURPOSE: Our aim was to estimate the perinatal risk factors associated with
      spontaneous preterm birth in the teenage parturient. METHODS: In a cohort study
      of all nulliparous teen (<=18-year old) deliveries over a 4-year period at one
      institution, we identified all cases of spontaneous preterm birth as defined by
      non-indicated delivery prior to 37 weeks of gestation. Analysis was performed
      using Fisher's exact, Student t test and logistic regression modeling. RESULTS:
      Of the 650 included teen deliveries, 88 (14 %) cases of spontaneous preterm birth
      were identified. Teenage mothers with spontaneous preterm birth had a
      significantly lower body mass index (BMI) (27.2 +/- 6.4 vs. 31.0 +/- 6.2, p =
      0.0001) and had lower gestational weight gain (14.4 +/- 6.6 vs. 11.2 +/- 5.0 kg,
      p = 0.0001) than those mothers with uncomplicated term births. In fact, a normal
      prepregnancy BMI (<25 kg/m(2)) placed the teen at elevated risk for spontaneous
      preterm birth (OR 3.35, 95 % CI 1.98-5.64), while prepregnancy obesity (30-35
      kg/m(2)) was protective (OR 0.26, 95 % CI 0.12-0.58). Controlling for potential
      confounders such as race, tobacco or illicit drug use, late prenatal care and
      sexually transmitted infections did not attenuate the above findings.
      CONCLUSIONS: Higher prepregnancy BMI, especially obesity, appears to be
      protective against spontaneous preterm birth in the nulliparous teen parturient.
      Further studies confirming this finding and investigation of potential underlying
      mechanisms of this association are warranted.

PMID- 24452739
TI  - Prostate cancer nomograms: a review of their use in cancer detection and
      treatment.
AB  - As prostate cancer treatment discussions have grown more complex, increasing
      numbers of nomograms to guide decision-making have been found in the literature.
      Such nomograms can influence every step in the prostate cancer therapeutic
      process, from determining the need for biopsy to the need for adjuvant therapy.
      With a properly counseled patient who is aware of the limitations of nomograms,
      such tools assist in the shared decision-making that characterizes modern
      informed consent. 

PMID- 24452740
TI  - Real-time elastography for the detection of prostate cancer.
AB  - The lack of reliable imaging tools in detecting prostate cancer makes a random
      biopsy still the standard of care to detect prostate cancer. To reduce the number
      of cores during a biopsy and therefore the risk of biopsy-related complications,
      an imaging tool which provides reliable guided biopsies is required. Transrectal
      real-time elastography has shown to have the ability to visualize prostate cancer
      foci to some extent. In addition to the conventional B-mode image of transrectal
      ultrasound, it adds information about the stiffness of the prostate tissue. This
      review highlights the most important studies on elastography to follow the
      improvements in techniques and to outline the ability to detect prostate cancer
      and guide biopsies. 

PMID- 24452742
TI  - Computational contributions to chemistry, biological chemistry and biophysical
      chemistry: the 2013 Nobel Prize in Chemistry.

PMID- 24452741
TI  - Identification of nitrated tyrosine residues of protein kinase G-Ialpha by mass
      spectrometry.
AB  - The nitration of tyrosine to 3-nitrotyrosine is an oxidative modification of
      tyrosine by nitric oxide and is associated with many diseases, and targeting of
      protein kinase G (PKG)-I represents a potential therapeutic strategy for
      pulmonary hypertension and chronic pain. The direct assignment of tyrosine
      residues of PKG-I has remained to be made due to the low sensitivity of the
      current proteomic approach. In order to assign modified tyrosine residues of PKG
      I, we nitrated purified PKG-Ialpha expressed in insect Sf9 cells by use of
      peroxynitrite in vitro and analyzed the trypsin-digested fragments by matrix
      assisted laser desorption/ionization-time of flight mass spectrometry and liquid
      chromatography-tandem mass spectrometry. Among the 21 tyrosine residues of PKG
      Ialpha, 16 tyrosine residues were assigned in 13 fragments; and six tyrosine
      residues were nitrated, those at Y71, Y141, Y212, Y336, Y345, and Y567, in the
      peroxynitrite-treated sample. Single mutation of tyrosine residues at Y71, Y212,
      and Y336 to phenylalanine significantly reduced the nitration of PKG-Ialpha; and
      four mutations at Y71, Y141, Y212, and Y336 (Y4F mutant) reduced it additively.
      PKG-Ialpha activity was inhibited by peroxynitrite in a concentration-dependent
      manner from 30 MUM to 1 mM, and this inhibition was attenuated in the Y4F mutant.
      These results demonstrated that PKG-Ialpha was nitrated at multiple tyrosine
      residues and that its activity was reduced by nitration of these residues. 

PMID- 24452743
TI  - Studies on the metabolism and the detectability of 4-methyl-amphetamine and its
      isomers 2-methyl-amphetamine and 3-methyl-amphetamine in rat urine using GC-MS
      and LC-(high-resolution)-MSn.
AB  - 4-Methyl-amphetamine (1-(4-methylphenyl)propane-2-amine; 4-MA) and its isomers 2
      methyl-amphetamine (2-MA) and 3-methyl-amphetamine (3-MA) belong to the group of
      amphetamine-type stimulants and of new psychoactive substances. Several studies
      showed similar potencies in releasing noradrenalin and dopamine, but higher
      potencies in releasing serotonin than amphetamine. In March 2013, the EU Council
      decided on an EU-wide control based on the European Monitoring Centre for Drugs
      and Drug Addiction risk assessment report documenting that 4-MA was sold as
      amphetamine on the illicit market and detected in several fatal cases. Therefore,
      4-MA and its isomers should be covered by drug testing in clinical and forensic
      toxicology. The aims of the presented work were to study the metabolism and
      detectability of each isomer in urine samples. For metabolism studies, rat urine
      samples were isolated by solid-phase extraction without and after enzymatic
      cleavage of conjugates. The phase I metabolites were separated and identified
      after acetylation by gas chromatography-mass spectrometry (GC-MS) and/or liquid
      chromatography-high resolution-linear ion trap mass spectrometry (LC-HR-MS(n))
      and the phase II metabolites by LC-HR-MS(n). From the identified phase I and II
      metabolites, the following main metabolic pathways were deduced: aromatic
      hydroxylation, hydroxylation of the phenylmethyl group followed by oxidation to
      the corresponding carboxylic acid, hydroxylation of the side chain, and
      glucuronidation and/or sulfation of the hydroxy and carboxy groups. CYP2D6 was
      involved in the aromatic hydroxylation. Finally, the intake of a commonly used
      dose of the MAs could be confirmed in rat urine using the authors' GC-MS and the
      LC-MS(n) standard urine screening approaches. Differentiation of the isomers to
      confirm the intake of a specific isomer was possible with an additional workup in
      rat urine.

PMID- 24452744
TI  - Rapid on-site TLC-SERS detection of four antidiabetes drugs used as adulterants
      in botanical dietary supplements.
AB  - A novel facile method has been established for rapid on-site detection of
      antidiabetes chemicals used to adulterate botanical dietary supplements (BDS) for
      diabetes. Analytes and components of pharmaceutical matrices were separated by
      thin-layer chromatography (TLC) then surface-enhanced Raman spectroscopy (SERS)
      was used for qualitative identification of trace substances on the HPTLC plate.
      Optimization and standardization of the experimental conditions, for example the
      method used for preparation of silver colloids, the mobile phase, and the
      concentration of colloidal silver, resulted in a very robust and highly sensitive
      method which enabled successful detection when the amount of adulteration was as
      low as 0.001 % (w/w). The method was also highly selective, enabling successful
      identification of some chemicals in extremely complex herbal matrices. The
      established TLC-SERS method was used for analysis of real BDS used to treat
      diabetes, and the results obtained were verified by liquid chromatography-triple
      quadrupole mass spectrometry (LC-MS-MS). The study showed that TLC-SERS could be
      used for effective separation and detection of four chemicals used to adulterate
      BDS, and would have good prospects for on-site qualitative screening of BDS for
      adulterants. 

PMID- 24452745
TI  - Elucidation of transformation pathway of ketoprofen, ibuprofen, and furosemide in
      surface water and their occurrence in the aqueous environment using UHPLC-QTOF
      MS.
AB  - The identification and determination of transformation products (TPs) of
      pharmaceuticals is essential nowadays, in order to track their fate in the
      aqueous environment and, thus, to estimate the actual pollution. However, this is
      a challenging task due to the necessity to apply high-resolution instruments
      enable to detect known and unknown compounds. This work presents the use of
      liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) as
      a powerful tool for the identification of three selected pharmaceuticals,
      furosemide (FUR), ibuprofen (IBP), and ketoprofen (KET), and their TPs in various
      water samples. Laboratory degradation experiments were performed using xenon lamp
      as a source of the irradiation in order to simulate phototransformation processes
      which may occur in the environment. Furthermore, the photodegradation kinetics of
      three selected compounds were assessed in a reactor equipped with xenon lamp in
      river water samples. Five TPs of IBP, seven of KET, and five of FUR were
      identified; some of them are presented here for the first time. Accurate mass
      measurements and fragmentation pattern obtained during an LC-QTOF-MS analysis
      allowed for structure elucidation of TPs followed by the creation of
      transformation pathway of selected pharmaceuticals. Finally, different water
      samples (wastewater influent and effluent, river water, untreated and treated
      water) were analyzed in order to estimate the presence of parent and transformed
      compounds. Only KET was detected in untransformed form in considered samples.
      Most of the TPs of selected drugs were found at least once in all water samples.
      Although IBP and FUR were not present in water samples as parent compounds, their
      different TPs occur. A great potential of LC-QTOF-MS in the identification and
      structural elucidation of TPs in the environment, allowing the recognition of the
      fate of pharmaceuticals in the environment through the determination of
      transformation pathway, has been presented. 

PMID- 24452747
TI  - Synthesis of diketopyrrolopyrrole based copolymers via the direct arylation
      method for p-channel and ambipolar OFETs.
AB  - In this paper, we have synthesized two novel diketopyrrolopyrrole (DPP) based
      donor-acceptor (D-A) copolymers poly{3,6-dithiophene-2-yl-2,5-di(2-octyl)
      pyrrolo[3,4-c]pyrrole-1,4-dione-alt-1,5-bis(dodecyloxy)naphthalene} (PDPPT-NAP)
      and poly{3,6-dithiophene-2-yl-2,5-di(2-butyldecyl)-pyrrolo[3,4-c]pyrrole-1,4
      dione-alt-2-dodecyl-2H-benzo[d][1,2,3]triazole} (PDPPT-BTRZ) via direct arylation
      organometallic coupling. Both copolymers contain a common electron withdrawing
      DPP building block which is combined with electron donating alkoxy naphthalene
      and electron withdrawing alkyl-triazole comonomers. The number average molecular
      weight (M(n)) determined by gel permeation chromatography (GPC) for polymer PDPPT
      NAP is around 23400 g mol(-1) whereas for polymer PDPPT-BTRZ it is 18600 g mol(
      1). The solid state absorption spectra of these copolymers show a wide range of
      absorption from 400 nm to 1000 nm with optical band gaps calculated from
      absorption cut off values in the range of 1.45-1.30 eV. The HOMO values
      determined for PDPPT-NAP and PDPPT-BTRZ copolymers from photoelectron
      spectroscopy in air (PESA) data are 5.15 eV and 5.25 eV respectively. These
      polymers exhibit promising p-channel and ambipolar behaviour when used as an
      active layer in organic thin-film transistor (OTFT) devices. The highest hole
      mobility measured for polymer PDPPT-NAP is around 0.0046 cm(2) V(-1) s(-1)
      whereas the best ambipolar performance was calculated for PDPPT-BTRZ with a hole
      and electron mobility of 0.01 cm(2) V(-1) s(-1) and 0.006 cm(2) V(-1) s(-1) .

PMID- 24452746
TI  - Effect of steady-state atorvastatin on the pharmacokinetics of a single dose of
      colchicine in healthy adults under fasted conditions.
AB  - BACKGROUND AND OBJECTIVE: Colchicine is commonly prescribed for gout. While
      minimally metabolized by the cytochrome P450 (CYP) 3A4 isoenzyme, colchicine is a
      substrate for P-glycoprotein (P-gp). Atorvastatin is metabolized primarily by
      CYP3A4 and is a P-gp inhibitor. Patients with gout often have dyslipidemia;
      therefore, the potential for co-administration of atorvastatin and colchicine
      exists. The objective of this study was to determine the effect of oral
      atorvastatin on the pharmacokinetics of a single, oral dose of colchicine.
      METHODS: Twenty-four healthy adult subjects were enrolled in this single-center,
      open-label, non-randomized, one-sequence, two-period drug-drug interaction study.
      On day 1, subjects received a single oral dose of colchicine 0.6 mg. After a 14
      day washout, subjects received atorvastatin 40 mg once daily for 14 days followed
      by a single dose of colchicine 0.6 mg co-administered with atorvastatin 40 mg on
      day 28. Main outcome measures were colchicine maximum plasma concentration (C
      max), area under the plasma concentration-time curve (AUC) from time zero to the
      last measurable concentration (AUC last), and AUC from time zero to infinity
      (AUCinfinity), which were compared with and without concurrent atorvastatin.
      RESULTS: Colchicine AUC last, AUCinfinity, and C max increased by 27, 24, and 31
      %, respectively, when co-administered with atorvastatin. Corresponding 90 %
      confidence intervals around the ratios were outside the established no-effect 80
      125 % interval. CONCLUSION: Increased colchicine exposure was observed after a
      single dose of colchicine was administered with steady-state atorvastatin.
      Additional studies with multiple dosing of both drugs are needed to further
      determine the clinical implications of these results.

PMID- 24452748
TI  - Should regionalization only be in 1 direction?

PMID- 24452749
TI  - Lab-on-a-chip technology: impacting non-invasive prenatal diagnostics (NIPD)
      through miniaturisation.
AB  - This paper aims to provide a concise review of non-invasive prenatal diagnostics
      (NIPD) to the lab-on-a-chip and microfluidics community. Having a market of over
      one billion dollars to explore and a plethora of applications, NIPD requires
      greater attention from microfluidics researchers. In this review, a complete
      overview of conventional diagnostic procedures including invasive as well as non
      invasive (fetal cells and cell-free fetal DNA) types are discussed. Special focus
      is given to reviewing the recent and past microfluidic approaches to NIPD, as
      well as various commercial entities in NIPD. This review concludes with future
      challenges and ethical considerations of the field. 

PMID- 24452750
TI  - Expression of microRNA-21 in non-small cell lung cancer tissue increases with
      disease progression and is likely caused by growth conditional changes during
      malignant transformation.
AB  - MicroRNAs can govern up to hundred different mRNAs and are important regulators
      of gene expression programs in development and disease. We analyzed the
      expression of microRNA-21, one of the most common oncomirs, in non-small cell
      lung cancer (NSCLC). Using northern blots the microRNA-21 expression levels of
      NSCLC-derived tissue and cell lines were measured. In line with earlier
      observations we show that mature microRNA-21 expression levels are highly
      increased in NSCLC-derived tissue compared to normal lung tissue. Additionally,
      we demonstrate that microRNA-21 levels correlate with malignancy since its
      expression in higher staged tumors is significantly more elevated compared to
      stage 1A. Interestingly, microRNA-21 levels in cultured NSCLC-derived cells are
      comparable to the expression detected in non-malignant lung tissue. Since
      microRNA-21 levels showed no fluctuation during the cell cycle, accelerated
      proliferation of tumor cells is not responsible for microRNA-21 upregulation in
      the tumor compartment. Similarly to NSCLC-derived cancer cells, the tumor
      associated fibroblasts show low expression levels of microRNA-21. Together, these
      data indicate that rather microenviromental and growth conditional changes than
      intrinsic features of the cancer cells are responsible for the observed increase
      of microRNA-21 levels in tumor tissues. Subsequently culturing conditions were
      changed to assess the impact of co-cultivation with fibroblasts, hypoxia and
      anchorage-independent growth on microRNA-21 expression. While co-cultivation with
      tumor-associated fibroblasts had no effect on microRNA-21 expression, both
      hypoxia and anchorage-independent growth cause a microRNA-21 elevation. In
      summary, our data demonstrate that growth conditions especially expected in more
      malignant tumors result in microRNA-21 upregulation explaining the observed
      increase in higher staged lung cancer tissue, but not in lung cancer-derived
      cells. 

PMID- 24452751
TI  - A pint of sweat will save a gallon of blood: a call for randomized trials of
      anticoagulation in end-stage renal disease.

PMID- 24452752
TI  - Warfarin use and the risk for stroke and bleeding in patients with atrial
      fibrillation undergoing dialysis.
AB  - BACKGROUND: Current observational studies on warfarin use and the risk for stroke
      and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found
      conflicting results. METHODS AND RESULTS: We conducted a population-based
      retrospective cohort study of patients aged >=65 years admitted to a hospital
      with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from
      1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and
      peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin
      users according to the first prescription filled for warfarin within 30 days
      after AF hospital discharge. We determined the association between warfarin use
      and the risk for stroke and bleeding in dialysis and nondialysis patients. The
      cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among
      dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among
      dialysis patients, warfarin users had more congestive heart failure and diabetes
      mellitus, but fewer prior bleeding events in comparison with the no-warfarin
      users. Among dialysis patients, warfarin use, in comparison with no-warfarin use,
      was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95%
      confidence interval, 0.78-1.67) but was associated with a 44% higher risk for
      bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13-1.85) after
      adjusting for potential confounders. Propensity score-adjusted analyses yielded
      similar results. CONCLUSIONS: Our results suggest that warfarin use is not
      beneficial in reducing stroke risk, but it is associated with a higher bleeding
      risk in patients with AF undergoing dialysis.

PMID- 24452753
TI  - R2 and R2* are equally effective in evaluating chronic response to iron
      chelation.
AB  - MRI relaxometry (R2, R2*) has generally replaced liver biopsy for estimation of
      liver iron stores in response to iron chelation, but there have been no
      longitudinal studies comparing R2 and R2* techniques. We use R2 and R2* liver
      iron concentration (LIC) estimates, transfusional iron burdens, and drug
      compliance data to calculate iron chelation efficiency (ICE) in patients
      undergoing a Phase II trial of SPD602. Fifty-one patients underwent a baseline
      examination, 39 patients completed 1 year, and 26 patients completed 2 years.
      Baseline LICR2 and LICR2* estimates were unbiased, but had limits of agreement
      exceeding 50%, suggesting that these techniques cannot be interchanged with one
      another in the same patient. However, ICE estimates across the two techniques
      compared more favorably, with r(2) values reaching 0.89 at 2 years. 95 confidence
      intervals for efficiency estimates were 0.0 +/- 4.1%. These data indicate that
      clinical trial and clinical effectiveness data calculated using LICR2 and LICR2*
      estimates can be compared to one another, even though LIC estimates may be
      disparate on cross-sectional analysis. While the choice of MRI assessment
      technique for clinical trials and for clinical management depends on many
      logistical considerations, one can have confidence comparing conclusions on
      clinical effectiveness.

PMID- 24452754
TI  - Prediction of protein kinase-specific phosphorylation sites in hierarchical
      structure using functional information and random forest.
AB  - Reversible protein phosphorylation is one of the most important post
      translational modifications, which regulates various biological cellular
      processes. Identification of the kinase-specific phosphorylation sites is helpful
      for understanding the phosphorylation mechanism and regulation processes.
      Although a number of computational approaches have been developed, currently few
      studies are concerned about hierarchical structures of kinases, and most of the
      existing tools use only local sequence information to construct predictive
      models. In this work, we conduct a systematic and hierarchy-specific
      investigation of protein phosphorylation site prediction in which protein kinases
      are clustered into hierarchical structures with four levels including kinase,
      subfamily, family and group. To enhance phosphorylation site prediction at all
      hierarchical levels, functional information of proteins, including gene ontology
      (GO) and protein-protein interaction (PPI), is adopted in addition to primary
      sequence to construct prediction models based on random forest. Analysis of
      selected GO and PPI features shows that functional information is critical in
      determining protein phosphorylation sites for every hierarchical level.
      Furthermore, the prediction results of Phospho.ELM and additional testing dataset
      demonstrate that the proposed method remarkably outperforms existing
      phosphorylation prediction methods at all hierarchical levels. The proposed
      method is freely available at http://bioinformatics.ustc.edu.cn/phos_pred/.

PMID- 24452755
TI  - Recurrence of left ventricular dysfunction in patients with restored idiopathic
      dilated cardiomyopathy.
AB  - BACKGROUND: In some patients with nonischemic idiopathic dilated cardiomyopathy
      (DCM), left ventricular (LV) dysfunction improves spontaneously but can recur.
      The factors predicting recurrence of LV dysfunction in recovered idiopathic DCM
      are poorly defined. We investigated the clinical, echocardiographic, and
      laboratory variables affecting recurrence of LV dysfunction in patients who
      recovered from DCM. HYPOTHESIS: The recurrence of LV dysfunction in recovered
      idiopathic DCM is impacted by clinical, echocardiographic, and laboratory
      variables. METHODS: The study comprised 85 consecutively enrolled patients (62
      males, age 57 +/- 16 years) with DCM who achieved a restoration of LV systolic
      function. Patients were followed up for 50 +/- 33 months after recovery from LV
      dysfunction without discontinuation of standard medication for heart failure with
      depressed ejection fraction. Clinical, echocardiographic, and laboratory
      variables were analyzed to identify factors independently associated with
      recurrence of LV dysfunction. RESULTS: LV dysfunction recurred in 33 patients (23
      males, age 64 +/- 12 years). Univariate analysis revealed that age, duration from
      initial presentation to recovery time, diabetes, and LV end-diastolic dimension
      (LVEDD) at initial presentation were associated with recurrence of LV
      dysfunction. Multivariate analysis revealed that only age, diabetes, and LVEDD at
      initial presentation were independent predictors in patients who recovered from
      LV dysfunction. CONCLUSIONS: The recurrence of LV dysfunction was significantly
      correlated with age, presence of diabetes, and LVEDD at initial presentation.
      Clinicians should consider maintenance of intensive care to patients who
      recovered from DCM with these factors.

PMID- 24452756
TI  - Sphingosine kinases/sphingosine-1-phosphate and death Signalling in APP
      transfected cells.
AB  - It has been postulated that disturbances in the sphingolipid metabolism play a
      key role in the pathogenesis of Alzheimer's disease (AD). An alteration in
      sphingosine kinases 1, 2 (SphK1/2) and sphingosine-1-phosphate (S1P) was recently
      reported in AD. However, the effect of AD-related amyloid beta (Abeta) peptides
      on SphK1/2 and the role of S1P in Abeta toxicity have not been fully elucidated.
      In this study the relationship between the Abeta concentration and SphK1/2
      expression/activity was analysed in PC12 cells transfected with the Abeta
      precursor protein, wild-type (APPwt) or bearing a double Swedish mutation
      (APPsw). The role of SphK(s)/S1P in cell survival and death was also
      investigated. Our results indicated that endogenously liberated Abeta
      significantly decreases expression and activity of SphK1/2. The SphK(s) inhibitor
      (SKI II, 10 MUM) decreased the viability of APPwt, APPsw as well as empty vector
      transfected PC12 control cells. Our data demonstrated that expression of S1P
      receptor-1 (S1P1) was significantly reduced in APP-transfected cells. The effect
      of S1P applied exogenously was cell type-dependent. In control and APPwt cells
      S1P reduced the effect of the SphK1 inhibitor on death signalling. Conversely, it
      decreased the survival of APPsw cells and had no protective effect on cells
      treated with SKI II. Using the S1P1 agonist (SEW2871, 5 MUM) and antagonist
      (W123, 20 MUM), we demonstrated that the cytoprotective effect of S1P was
      receptor-independent. Summarising, we showed that Abeta peptides evoke down
      regulation of gene expression and activity for SphK(s) and S1P1. Inhibition of
      SphK(s) significantly decreased cell survival. The effect of exogenous S1P
      depended on the concentration of Abeta peptides. 

PMID- 24452757
TI  - Pancreatic NETs: where do we stand now?
AB  - The systemic management of patients with pancreatic neuroendocrine tumors
      includes chemotherapy and targeted agents such as everolimus and sunitinib. Which
      treatment to favor in a particular patient is not known. The most commonly used
      chemotherapy agents are streptozocin and temozolamide, often prescribed in
      combination with fluoropyrimidines. A potential biomarker for selection of
      temozolomide-based chemotherapy is O-6-methylguanine-DNA-methyltrasferase
      expression. Chemotherapy yields higher response rates and may be preferable in
      patients with higher-grade tumors and those who are symptomatic. The mammalian
      target of rapamycin inhibitor everolimus has shown improvement in progression
      free survival (PFS) in a robust, well-conducted phase III study. Everolimus,
      however, can induce limiting toxicities that may result in treatment
      discontinuation and does not improve survival. However, the objective response
      rate is very low. Sunitinib, likewise, increases PFS but the data comes from a
      smaller trial which was terminated early. Sunitinib displays a different toxicity
      profile and is associated with a trend towards improved overall survival. It is
      clear that biomarkers to properly select the most effective agents in an
      individual patient are needed.

PMID- 24452758
TI  - Metastatic castration-resistant prostate cancer (CRPC): preclinical and clinical
      evidence for the sequential use of novel therapeutics.
AB  - With five novel therapies shown to improve survival in metastatic castration
      resistant prostate cancer (CRPC) in the last 3 years, patients are now living
      longer and experiencing better quality of life. Since docetaxel became standard
      of care for men with symptomatic metastatic CRPC, three artificial treatment
      "spaces" have emerged for prostate cancer drug development: pre-docetaxel,
      docetaxel combinations, and following docetaxel. Multiple therapies are currently
      under development in both early and late stage CRPC. Additionally, the novel
      agents abiraterone, radium-223, cabazitaxel, and enzalutamide have all been
      approved in the post-docetaxel setting. Strategies for patient selection and
      treatment sequencing are therefore urgently required. In this comprehensive
      review, we will summarize the preclinical and clinical data available with
      regards to sequencing of the novel treatments for CRPC. 

PMID- 24452760
TI  - [Cardiac surgery in underlying chronic pulmonary disease. Prognostic implications
      and efficient preoperative evaluation].
AB  - Cardiac surgery in patients with chronic pulmonary diseases carries a high risk
      of postoperative pulmonary complications (ppc) because both are known to cause
      ppc. Autopsy studies have revealed ppc as the main cause of mortality in
      approximately 5-8% of patients after cardiac surgery. Not all pulmonary diseases
      are high risk comorbidities in cardiac surgery: whereas chronic obstructive
      pulmonary disease (COPD) and obstructive sleep apnea significantly increase the
      risk of ppc, a well controlled asthma does not carry an additional risk of ppc. A
      thorough preoperative risk stratification is crucial for risk estimation and some
      validated risk calculators, such as the Canet risk score exist. Surprisingly the
      additional value of pulmonary function testing beyond a thorough patient history
      and physical examination is low. No validated thresholds exist in pulmonary
      function testing below which cardiac surgery should be denied if clearly
      indicated. Perioperative strategies for risk reduction should be applied to all
      patients whenever possible. 

PMID- 24452759
TI  - Mouse models of prostate cancer: picking the best model for the question.
AB  - When the National Institutes of Health Mouse Models of Human Cancer Consortium
      initiated the Prostate Steering Committee 15 years ago, there were no genetically
      engineered mouse (GEM) models of prostate cancer (PCa). Today, a PubMed search
      for "prostate cancer mouse model" yields 3,200 publications and this list
      continues to grow. The first generation of GEM utilized the newly discovered and
      characterized probasin promoter driving viral oncogenes such as Simian virus 40
      large T antigen to yield the LADY and TRAMP models. As the PCa research field has
      matured, the second generation of models has incorporated the single and multiple
      molecular changes observed in human disease, such as loss of PTEN and
      overexpression of Myc. Application of these models has revealed that mice are
      particularly resistant to developing invasive PCa, and once they achieve invasive
      disease, the PCa rarely resembles human disease. Nevertheless, these models and
      their application have provided vital information on human PCa progression. The
      aim of this review is to provide a brief primer on mouse and human prostate
      histology and pathology, provide descriptions of mouse models, as well as attempt
      to answer the age old question: Which GEM model of PCa is the best for my
      research question? 

PMID- 24452761
TI  - [Medical therapy of heart and lung diseases. Effects on the respective other
      organ].
AB  - Many patients suffer from both heart and lung diseases. The choice of medical
      drugs should not only be driven by the clinical and prognostic effects on the
      target organ but should also be selected based on the effects on the respective
      other organ. Beta blockers and statins have both beneficial and harmful effects
      on the respiratory system. Angiotensin-converting enzyme (ACE) inhibitors and
      amiodarone can cause severe lung damage. Low-dose thiazides and calcium
      antagonists are first-line medications in hypertensive asthma patients but beta
      blockers should be avoided. Theophyline should be used with caution in patients
      with known cardiac disease. Glucocorticosteroids can cause cardiovascular
      symptoms while the phosphodiesterase inhibitor roflumilast appears to have no
      relevant cardiovascular side effects. Anticholinergic drugs have both favorable
      and unfavorable cardiovascular (side) effects. Short-acting beta-2
      sympathomimetic drugs (SABA) and macrolides in particular can trigger arrhythmia
      and some SABAs are associated with a higher incidence of myocardial infarction.
      Detailed knowledge of the effects of drugs used for the treatment of lung and
      heart diseases on the respective other organ and the associated complications and
      long-term effects are essential in providing optimal medical care to the many
      patients who present with both respiratory and cardiovascular diseases. 

PMID- 24452762
TI  - [Heart and combined heart-lung transplantation. Indications, chances and risks].
AB  - Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold
      standard for the treatment of terminal heart failure. The main indications for
      HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the
      acute phase after HTX the survival rate is approximately 90%. Good short and long
      term results with survival rates ranging from 81% after 1 year to more than 50%
      after 11 years demonstrate that there is currently no real treatment alternative
      to HTX for treatment of end-stage heart failure. In the case of irreversible
      pulmonary hypertension in combination with end-stage heart failure or complex
      congenital heart syndromes, a combined heart and lung transplantation (HLTX) is
      necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly
      for technical reasons. Improved long-term results after HTX and HLTX are a result
      of highly specialized transplantation units and effective immunosuppression.
      However, a major problem is the shortage of organ donors in Germany and the
      resulting long waiting times for patients with frequently occurring blood groups
      of up to 10 months for transplantation. The consequence of the latter is the ever
      increasing number of implanted cardiac assist devices in patients not only as a
      bridge to transplant but also as destination therapy. 

PMID- 24452763
TI  - Effects of unilateral phrenic nerve stimulation on tidal volume. First case
      report of a patient responding to remede(r) treatment for nocturnal Cheyne-Stokes
      respiration.

PMID- 24452764
TI  - Slow deactivation channels in UV-photoexcited adenine DNA.
AB  - The molecular mechanism for removing the excess energy in DNA bases is
      responsible for the high photostability of DNA and is thus the subject of intense
      theoretical/computational investigation. To understand why the excited state
      decay of the stacked bases is significantly longer than that of the monomers, we
      carried out electronic structure calculations on an adenine monomer and an
      aqueous (dA)5 oligonucleotide employing the CASPT2//CASSCF and
      CASPT2//CASSCF/AMBER levels of theory. The newly-found bright excited state pair
      Sstack1((1)pipi*) and Sstack2((1)pipi*) of d(A)5, originated from base stacking,
      is of intra-base charge transfer nature and occurs in different stacked bases
      with charge transfer along opposite directions. Two slow deactivation channels of
      d(A)5 were proposed as a result of the sizable barriers along the relaxation
      paths starting from the FC point of the Sstack1((1)pipi*) state. The
      SN1P((1)npi*) state of d(A)5 serves as an intermediate state in one relaxation
      channel, to which a nonadiabatic decay from the Sstack1((1)pipi*) state occurs in
      an energy degeneracy region. A relatively high barrier in this state is found and
      attributed to the steric hindrance of the DNA environment due to the large NH2
      group twisting, which gives a weak and red-shifted fluorescence. Another direct
      relaxation channel, induced by the C2-H2 bond twisting motion, is found to go
      through a conical intersection between the Sstack1((1)pipi*) and the ground
      state. The barrier found here enables fluorescence from the Sstack1((1)pipi*)
      state and may explain the bright state emission observed in the fluorescence
      upconversion measurements. The inter-molecular SCT((1)pipi*) state may be
      involved in the slow relaxation process of the photoexcited adenine oligomers
      through efficient internal conversion to the intra-base Sstack1((1)pipi*) state. 

PMID- 24452765
TI  - An Exploration of Sexual Victimization and Academic Performance Among College
      Women.
AB  - The literature has documented the widespread nature of sexual assault
      victimization among college women. While the aftermath of violence against
      university women has also received focus, that is, documenting trauma-related
      sequelae; risk factors; reporting patterns; and legal interventions, the impact
      on academic performance has not received adequate attention in the literature.
      The primary purpose of this study was to explore the association of rape and
      sexual assault with academic performance among college women. Its specific aims
      included the following: to compare high school and college sexual assault
      experiences with collegiate grade point averages (GPAs) at key points in time; to
      examine any differences in GPA by type of sexual assault; to urge researchers
      studying retention and persistence patterns or sexual assault among college
      students to ensure that the relationship between the two is included in research
      designs; and to recommend that academic institutions expand programming on
      retention to include rape and sexual assault among the risk factors associated
      with a lack of persistence.

PMID- 24452766
TI  - Vertigo and imbalance.

PMID- 24452767
TI  - Two is better than one: physical interactions improve motor performance in
      humans.
AB  - How do physical interactions with others change our own motor behavior? Utilizing
      a novel motor learning paradigm in which the hands of two - individuals are
      physically connected without their conscious awareness, we investigated how the
      interaction forces from a partner adapt the motor behavior in physically
      interacting humans. We observed the motor adaptations during physical
      interactions to be mutually beneficial such that both the worse and better of the
      interacting partners improve motor performance during and after interactive
      practice. We show that these benefits cannot be explained by multi-sensory
      integration by an individual, but require physical interaction with a reactive
      partner. Furthermore, the benefits are determined by both the interacting
      partner's performance and similarity of the partner's behavior to one's own. Our
      results demonstrate the fundamental neural processes underlying human physical
      interactions and suggest advantages of interactive paradigms for sport-training
      and physical rehabilitation. 

PMID- 24452768
TI  - Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease.
AB  - OPINION STATEMENT: While anti-TNF agents have had a marked impact in the
      treatment of inflammatory bowel disease, a significant number of patients lose
      their response to these medications over time. Clinical trials have demonstrated
      that antibodies against anti-TNF medications may impact treatment response and
      increase the risk of infusion reaction. Scheduled dosing and concurrent use of
      immunomodulators may help to mitigate these risks via inhibiting the formation of
      these antibodies. The recent availability of assays to measure anti-TNF drug
      levels and antibodies against anti-TNFs offer the opportunity to assess patients
      who have lost response with infliximab and adalimumab, and potentially determine
      the most appropriate therapeutic strategy. There is growing evidence that such
      testing improves patient outcomes and is cost-effective, although heterogeneity
      in the assays used in clinical and observational trials has resulted in mixed
      results.

PMID- 24452769
TI  - Automated analysis of background EEG and reactivity during therapeutic
      hypothermia in comatose patients after cardiac arrest.
AB  - Visual analysis of electroencephalography (EEG) background and reactivity during
      therapeutic hypothermia provides important outcome information, but is time
      consuming and not always consistent between reviewers. Automated EEG analysis may
      help quantify the brain damage. Forty-six comatose patients in therapeutic
      hypothermia, after cardiac arrest, were included in the study. EEG background was
      quantified with burst-suppression ratio (BSR) and approximate entropy, both used
      to monitor anesthesia. Reactivity was detected through change in the power
      spectrum of signal before and after stimulation. Automatic results obtained
      almost perfect agreement (discontinuity) to substantial agreement (background
      reactivity) with a visual score from EEG-certified neurologists. Burst
      suppression ratio was more suited to distinguish continuous EEG background from
      burst-suppression than approximate entropy in this specific population. Automatic
      EEG background and reactivity measures were significantly related to good and
      poor outcome. We conclude that quantitative EEG measurements can provide
      promising information regarding current state of the patient and clinical
      outcome, but further work is needed before routine application in a clinical
      setting. 

PMID- 24452770
TI  - Dissociating conscious and unconscious learning with objective and subjective
      measures.
AB  - According to functionalist theories, consciousness can be defined by the
      functions that it serves and by the way it contributes to cognition. For example,
      when trying to establish dissociations between conscious and unconscious
      knowledge, conscious representations would be identified by the fact that they
      allow cognitive control or successful identification or recollection, assessed by
      verbal reports or forced-choice tasks. Even though the functionalist approach has
      brought about important dissociation results concerning conscious and unconscious
      cognition, critics emphasize that it does not account for the qualitative
      properties of conscious experience. Phenomenal theories are precisely based on
      the notion that conscious representations are such that it feels like something
      to have these representations. Thus, one way to assess conscious knowledge is to
      ask people, after they have produced a forced-choice response, to identify their
      mental states through the use of subjective confidence ratings, in which they
      discriminate between a complete guess and a response based on some feeling of
      knowing. However, these 2 approaches are not mutually exclusive. In this article,
      we review a series of studies showing that the joint use of objective judgments
      about some external stimuli and about one's own subjective knowledge concerning
      these stimuli, provides new insights into the putative dissociation between
      conscious and unconscious knowledge in learning. 

PMID- 24452771
TI  - Endolymphatic sac involvement in bacterial meningitis.
AB  - The commonest sequelae of bacterial meningitis are related to the inner ear.
      Little is known about the inner ear immune defense. Evidence suggests that the
      endolymphatic sac provides some protection against infection. A potential
      involvement of the endolymphatic sac in bacterial meningitis is largely
      unaccounted for, and thus the object of the present study. A well-established
      adult rat model of Streptococcus pneumoniae meningitis was employed. Thirty adult
      rats were inoculated intrathecally with Streptococcus pneumoniae and received no
      additional treatment. Six rats were sham-inoculated. The rats were killed when
      reaching terminal illness or on day 7, followed by light microscopy preparation
      and PAS-Alcian blue staining. The endolymphatic sac was examined for bacterial
      invasion and leukocyte infiltration. Neither bacteria nor leukocytes infiltrated
      the endolymphatic sac during the first days. Bacteria invaded the inner ear
      through the cochlear aquaduct. On days 5-6, the bacteria invaded the
      endolymphatic sac through the endolymphatic duct subsequent to invasion of the
      vestibular endolymphatic compartment. No evidence of direct bacterial invasion of
      the sac through the meninges was found. Leukocyte infiltration of the sac
      occurred prior to bacterial invasion. During meningitis, bacteria do not invade
      the endolymphatic sac through the dura, but solely through the endolymphatic
      duct, following the invasion of the vestibular system. Leukocyte infiltration of
      the sac occurs prior to, as well as concurrent with bacterial invasion. The
      findings support the endolymphatic sac as part of an innate immune defense system
      protecting the inner ear from infection. 

PMID- 24452772
TI  - The clinical characteristics and treatment for sudden sensorineural hearing loss
      with vestibular schwannoma.
AB  - The aim of this study is to analyze the clinical characteristics and treatment of
      sudden sensorineural hearing loss (SSNHL) patients with vestibular schwannoma
      (VS). The clinical features of the VS patients were explored by retrospectively
      analyzing the clinical data from 542 cases of SSNHL patients between January 2008
      and March 2013. There were 10 cases (10 ears) diagnosed with VS in 542 cases of
      SSNHL patients (10 ears, 1.85 %), 3 males, 7 females, with a range of 28-57
      years. Among all the cases, eight patients with abnormal ABR, ten with ear
      ipsilateral stapedius reflexes which were completely not elicited and seven
      patients with healthy ear contralateral stapedius reflexes which were completely
      not elicited. Neuromas were classified by Koos grades according to size (8 of
      grade I, 1 of grade II, 1 of grade IV). Eight small VS  patients were taken
      waiting and MRI therapy strategies. Meanwhile, we used glucocorticoid treatment
      and timely and short-term medication to improve the microcirculation of the inner
      ear for these patients. And four cases' hearing was improved. Some vestibular
      schwannomas have SSNHL as initial symptoms, especially the small ones in internal
      auditory canal. To prevent misdiagnosis or leak-diagnosis, MRI should be
      performed as a routine test for SSNHL, and ABR is sometimes necessary for SSNHL
      patients. It is also necessary to give appropriate treatment to protect hearing
      of the small vestibular schwannoma patients whose first symptoms are diagnosed as
      SSNHL in acute phase. 

PMID- 24452773
TI  - Air, bone and soft tissue excitation of the cochlea in the presence of severe
      impediments to ossicle and window mobility.
AB  - Clinical conditions have been described in which one of the two cochlear windows
      is immobile (otosclerosis) or absent (round window atresia), but nevertheless
      bone conduction (BC) thresholds are relatively unaffected. To clarify this
      apparent paradox, experimental manipulations which would severely impede several
      of the classical osseous mechanisms of BC were induced in fat sand rats,
      including discontinuity or immobilization of the ossicular chain, coupled with
      window fixation. Effects of these manipulations were assessed by recording
      auditory nerve brainstem evoked response (ABR) thresholds to stimulation by air
      conduction (AC), by osseous BC and by non-osseous BC (also called soft tissue
      conduction-STC) in which the BC bone vibrator is applied to skin sites. Following
      the immobilization, discontinuity and window fixation, auditory stimulation was
      also delivered to cerebro-spinal fluid (CSF) and to saline applied to the middle
      ear cavity. While the manipulations (immobilization, discontinuity, window
      fixation) led to an elevation of AC thresholds, nevertheless, there was no change
      in osseous and non-osseous BC thresholds. On the other hand, ABR could be
      elicited in response to fluid pressure stimulation to CSF and middle ear saline,
      even in the presence of the severe restriction of ossicular chain and window
      mobility. The results of these experiments in which osseous and non-osseous BC
      thresholds remained unchanged in the presence of severe restriction of the
      classical middle ear mechanisms and in the absence of an efficient release
      window, while ABR could be recorded in response to fluid pressure auditory
      stimulation to fluid sites, indicate that it is possible that the inner ear may
      be activated at low sound intensities by fast fluid pressure stimulation. At
      higher sound intensities, a slower passive basilar membrane traveling wave may
      serve to excite the inner ear. 

PMID- 24452774
TI  - Haemophilia A mutations in patients with non-severe phenotype associated with a
      discrepancy between one-stage and chromogenic factor VIII activity assays.
AB  - About one-third of patients with non-severe haemophilia A (HA) show a discrepancy
      of factor (F)VIII activity (FVIII:C) measured by one-stage (FVIII:C1st), two
      stage assays or the chromogenic method (FVIII:Cchr). The aim of the study was to
      characterise the mutation profile in patients with FVIII:C assay discrepancies.
      FVIII:C discrepancy was considered significant if the calculated ratio between
      FVIII:C1st and FVIII:Cchr was <= 0.6. In 16 patients FVIII:C1st was higher than
      FVIII:Cchr. The reversephenomenon was observed in 83 patients. Genetic analysis
      revealed 23 different missense mutations of which 17 were novel. Most mutations,
      exhibiting a higher FVIII:C1st were localised in the A1-A2-A3 interface. The
      majority of mutations associated with FVIII:Cchr>FVIII:C1st discrepancy were
      located close to or within the thrombin cleavage sites, FIX or vWF binding sites.
      Our data show a correlation between FVIII:C and thrombin generation testing with
      a clear differentiation between patients with haemophilia and normal controls.
      However, in the subgroup of FVIII:C1st>FVIII:Cchr discrepancy, the endogenous
      thrombin potential and peak thrombin parameters were similar to non-discrepant
      haemophilia patients, while in the inverse discrepancy FVIII:Cchr>FVIII:C1st,
      these variables showed values close to that of the normal control group. Certain
      hereditary F8 missense mutations cause discrepancy in FVIII:C as measured with
      different assays. This can lead to failure in diagnosing HA or incorrectly
      classifying the severity of the disease. Therefore, we recommend that initial
      diagnosis of non-severe HA phenotypes should be based on results of both
      FVIII:C1st and FVIII:Cchr assays. 

PMID- 24452775
TI  - Diagnostic performance of copeptin in patients with acute nontraumatic chest
      pain: BWH-TIMI ED chest pain study.
AB  - BACKGROUND: Arginine-vasopressin (AVP) is an acute marker of physiologic stress.
      Copeptin is the C-terminal fragment of vasopressin precursor hormone that is more
      easily measured than AVP. Studies assessing the utility of copeptin in the
      diagnosis of myocardial infarction (MI) have demonstrated mixed results.
      HYPOTHESIS: The aim of this study was to test the hypothesis that copeptin
      improves diagnostic performance when added to troponin for detecting MI in
      patients presenting to the emergency department with nontraumatic chest pain.
      METHODS: We measured copeptin, local cardiac troponin I (local cTnI), and a
      contemporary sensitive cardiac troponin I (sensitive cTnI) at presentation and
      serially in patients who presented with acute chest pain. A copeptin cutoff of 14
      pmol/L was utilized. RESULTS: MI was diagnosed in 25.7% of patients. Noncoronary
      acute cardiopulmonary causes of chest pain occurred in 12.8%. Patients with MI
      had significantly higher copeptin levels than patients with noncardiac chest pain
      (P < 0.001). The area under the receiver operating characteristic curve (AUC) for
      copeptin was 0.60 (95% confidence interval: 0.54-0.66), significantly less than
      the AUC for local cTnI (0.92) or sensitive cTnI (0.96). The combination of
      copeptin with either the local or sensitive troponin assay (c-statistics 0.92 and
      0.95, respectively) did not significantly improve the AUC as compared to either
      troponin assay alone. This finding persisted in the subgroup of early presenters
      (<= 6 hours from symptom onset). CONCLUSIONS: Copeptin did not improve the
      diagnostic performance for detecting MI when used alone or in combination with a
      contemporary sensitive cTnI assay, though our cohort had relatively few early
      presenters.

PMID- 24452776
TI  - Ventromedial prefrontal cortex activity and rapid eye movement sleep are
      associated with subsequent fear expression in human subjects.
AB  - In humans, activity patterns in the ventromedial prefrontal cortex (vmPFC) have
      been found to be predictive of subsequent fear memory consolidation. Pioneering
      work in rodents has further shown that vmPFC-amygdala theta synchronization is
      correlated with fear memory consolidation. We aimed to evaluate whether vmPFC
      activity during fear conditioning is (1) correlated with fear expression the
      subsequent day and whether (2) this relationship is mediated by rapid eye
      movement (REM) sleep. We analyzed data from 17 young healthy subjects undergoing
      a fear conditioning task, followed by a fear extinction task 24 h later, both
      recorded with simultaneous skin conductance response (SCR) and functional
      magnetic resonance imaging measurements, with a polysomnographically recorded
      night sleep in between. Our results showed a correlation between vmPFC activity
      during fear conditioning and subsequent REM sleep amount, as well as between REM
      sleep amount and SCR to the conditioned stimulus 24 h later. Moreover, we
      observed a significant correlation between vmPFC activity during fear
      conditioning and SCR responses during extinction, which was no longer significant
      after controlling for REM sleep amount. vmPFC activity during fear conditioning
      was further correlated with sleep latency. Interestingly, hippocampus activity
      during fear conditioning was correlated with stage 2 and stage 4 sleep amount.
      Our results provide preliminary evidence that the relationship between REM sleep
      and fear conditioning and extinction observed in rodents can be modeled in
      healthy human subjects, highlighting an interrelated set of potentially relevant
      trait markers.

PMID- 24452777
TI  - The effect of movement kinematics on predicting the timing of observed actions.
AB  - The ability to predict the actions of other agents is vital for joint action
      tasks. Recent theory suggests that action prediction relies on an emulator system
      that permits observers to use a model of their own movement kinematics to predict
      the actions of other agents. If this is the case, then people should be more
      accurate at generating predictions about actions that are similar to their own.
      We tested this hypothesis in two experiments in which participants were required
      to predict the occurrence and timing of particular critical points in an observed
      action. In Experiment 1, we employed a self/other prediction paradigm in which
      prediction accuracy for recordings of self-generated movements was compared with
      prediction accuracy for recordings of other-generated movements. As expected,
      prediction was more accurate for recordings of self-generated actions because in
      this case the movement kinematics of the observer and observed stimuli are
      maximally similar. In Experiment 1, people were able to produce actions at their
      own tempo and, therefore, the results might be explained in terms of self
      similarity in action production tempo rather than in terms of movement
      kinematics. To control for this possibility in Experiment 2, we compared
      prediction accuracy for stimuli that were matched in tempo but differed only in
      terms of kinematics. The results showed that participants were more accurate when
      predicting actions with a human kinematic profile than tempo-matched stimuli that
      moved with non-human kinematics. Finally, in Experiment 3, we confirmed that the
      results of Experiment 2 cannot be explained by human-like stimuli containing a
      slowing down phase before the critical points. Taken together, these findings
      provide further support for the role of motor emulation in action prediction, and
      they suggest that the action prediction mechanism produces output that is
      available rapidly and available to drive action control suggesting that it can
      plausibly support joint action coordination. 

PMID- 24452778
TI  - Positive and negative volume-outcome relationships in the geriatric trauma
      population.
AB  - IMPORTANCE: In trauma populations, improvements in outcome are documented in
      institutions with higher case volumes. However, it is not known whether improved
      outcomes are attributable to the case volume within specific higher-risk groups,
      such as the elderly, or to the case volume among all trauma patients treated by
      an institution. OBJECTIVE: To test the hypothesis that outcomes of trauma care
      for geriatric patients are affected differently by the volume of geriatric cases
      and nongeriatric cases of an institution. DESIGN, SETTING, AND PARTICIPANTS: This
      retrospective cohort study using a statewide trauma registry was set in state
      designated levels 1 and 2 trauma centers in Pennsylvania. It included 39 431
      eligible geriatric trauma patients (aged >65 years) in the Pennsylvania Trauma
      Outcomes Study. MAIN OUTCOMES AND MEASURES: In-hospital mortality, major
      complications, and mortality after major complications (failure to rescue).
      RESULTS: Between 2001 and 2010, 39 431 geriatric trauma patients and 105 046
      nongeriatric patients were captured in a review of outcomes in 20 state
      designated levels 1 and 2 trauma centers. Larger volumes of geriatric trauma
      patients were significantly associated with lower odds of in-hospital mortality,
      major complications, and failure to rescue. In contrast, larger nongeriatric
      trauma volumes were significantly associated with higher odds of major
      complications in geriatric patients. CONCLUSIONS AND RELEVANCE: Higher rates of
      in-hospital mortality, major complications, and failure to rescue were associated
      with lower volumes of geriatric trauma care and paradoxically with higher volumes
      of trauma care for younger patients. These findings offer the possibility that
      outcomes might be improved with differentiated pathways of care for geriatric
      trauma patients.

PMID- 24452779
TI  - Association of a polymorphism of BTN2A1 with dyslipidemia in community-dwelling
      individuals.
AB  - We have previously shown that the C->T polymorphism (rs6929846) of the
      butyrophilin, subfamily 2, member A1 gene (BTN2A1) was significantly associated
      with myocardial infarction. Considering that dyslipidemia is a significant risk
      factor for coronary heart disease, it was hypothesized that the association
      between rs6929846 of BTN2A1 and myocardial infarction may be attributable, at
      least in part, to its effect on the susceptibility to dyslipidemia. The purpose
      of the present study was to examine a possible association of rs6929846 of BTN2A1
      with dyslipidemia in community-dwelling individuals. The study subjects were
      comprised of 5,958 community-dwelling individuals (2,909 subjects with
      dyslipidemia and 3,049 controls) who were recruited into a population-based
      cohort study in Inabe, Japan. Dyslipidemia was defined by a serum concentration
      of triglycerides of >=1.65 mmol/l, a serum high-density lipoprotein-cholesterol
      concentration of <1.04 mmol/l or a serum low-density lipoprotein (LDL)
      cholesterol concentration of >=3.64 mmol/l. A comparison of the allele
      frequencies or genotype distributions by the chi2 test revealed that rs6929846 of
      BTN2A1 was significantly associated with dyslipidemia (P<0.05). A multivariable
      logistic regression analysis adjusted for age, gender, body mass index, smoking
      status and the prevalence of diabetes mellitus revealed that rs6929846 of BTN2A1
      was significantly (dominant model; P=2.4x10-4; odds ratio, 1.29) associated with
      dyslipidemia, with the minor T allele representing a risk for this condition.
      Among all the individuals, the serum concentrations of total cholesterol,
      triglycerides and LDL-cholesterol were significantly greater for individuals in
      the combined CT and TT genotype groups than for those with the CC genotype.
      BTN2A1 may thus be a susceptibility gene for dyslipidemia in community-dwelling
      individuals.

PMID- 24452780
TI  - The CNR continues to grow; the editorial board keeps pace.

PMID- 24452784
TI  - EWOD (electrowetting on dielectric) digital microfluidics powered by finger
      actuation.
AB  - We report finger-actuated digital microfluidics (F-DMF) based on the manipulation
      of discrete droplets via the electrowetting on dielectric (EWOD) phenomenon.
      Instead of requiring an external power supply, our F-DMF uses piezoelectric
      elements to convert mechanical energy produced by human fingers to electric
      voltage pulses for droplet actuation. Voltage outputs of over 40 V are provided
      by single piezoelectric elements, which is necessary for oil-free EWOD devices
      with thin (typically <1 MUm) dielectric layers. Higher actuation voltages can be
      provided using multiple piezoelectric elements connected in series when needed.
      Using this energy conversion scheme, we confirmed basic modes of EWOD droplet
      operation, such as droplet transport, splitting and merging. Using two
      piezoelectric elements in series, we also successfully demonstrated applications
      of F-DMF for glucose detection and immunoassay. Not requiring power sources, F
      DMF offers intriguing paths for various portable and other microfluidic
      applications. 

PMID- 24452783
TI  - Tribe-specific satellite DNA in non-domestic Bovidae.
AB  - Satellite sequences present in the centromeric and pericentric regions of
      chromosomes represent useful source of information. Changes in satellite DNA
      composition may coincide with the speciation and serve as valuable markers of
      phylogenetic relationships. Here, we examined satellite DNA clones isolated by
      laser microdissection of centromeric regions of 38 bovid species and categorized
      them into three types. Sat I sequences from members of
      Bovini/Tragelaphini/Boselaphini are similar to the well-documented 1.715 sat I
      DNA family. Sat I DNA from
      Caprini/Alcelaphini/Hippotragini/Reduncini/Aepycerotini/Cephalophini/Antilopini/N
      otragini/Oreotragini form the second group homologous to the common 1.714 sat I
      DNA. The analysis of sat II DNAs isolated in our study confirmed conservativeness
      of these sequences within Bovidae. Newly described centromeric clones from
      Madoqua kirkii and Strepsiceros strepsiceros were similar in length and
      repetitive tandem arrangement but showed no similarity to any other satellite DNA
      in the GenBank database. Phylogenetic analysis of sat I sequences isolated in our
      study from 38 bovid species enabled the description of relationships at the
      subfamily and tribal levels. The maximum likelihood and Bayesian inference
      analyses showed a basal position of sequences from Oreotragini in the subfamily
      Antilopinae. According to the Bayesian inference analysis based on the indels in
      a partitioned mixed model, Antilopinae satellite DNA split into two groups with
      those from Neotragini as a basal tribe, followed by a stepwise, successive
      branching of Cephalophini, Aepycerotini and Antilopini sequences. In the second
      group, Reduncini sequences were basal followed by Caprini, Alcelaphini and
      Hippotragini. 

PMID- 24452785
TI  - Optimization of amorphous silicon double junction solar cells for an efficient
      photoelectrochemical water splitting device based on a bismuth vanadate
      photoanode.
AB  - A photoelectrochemical water splitting device (PEC-WSD) was designed and
      fabricated based on cobalt-phosphate-catalysed and tungsten-gradient-doped
      bismuth vanadate (W:BiVO4) as the photoanode. A simple and cheap hydrogenated
      amorphous silicon (a-Si:H) double junction solar cell has been used to provide
      additional bias. The advantage of using thin film silicon (TF-Si) based solar
      cells is that this photovoltaic (PV) technology meets the crucial requirements
      for the PV component in PEC-WSDs based on W:BiVO4 photoanodes. TF-Si PV devices
      are stable in aqueous solutions, are manufactured by simple and cheap fabrication
      processes and their spectral response, voltage and current density show an
      excellent match with the photoanode. This paper is mainly focused on the
      optimization of the TF-Si solar cell with respect to the remaining solar spectrum
      transmitted through the W:BiVO4 photoanode. The current matching between the top
      and bottom cells is studied and optimized by varying the thickness of the a-Si:H
      top cell. We support the experimental optimization of the current balance between
      the two sub-cells with simulations of the PV devices. In addition, the impact of
      the light induced degradation of the a-Si:H double junction, the so-called
      Staebler-Wronski Effect (SWE), on the performance of the PEC-WSD has been
      studied. The light soaking experiments on the a-Si:H/a-Si:H double junctions over
      1000 hours show that the efficiency of a stand-alone a-Si:H/a-Si:H double
      junction cell is significantly reduced due to the SWE. Nevertheless, the SWE has
      a significantly smaller effect on the performance of the PEC-WSD. 

PMID- 24452786
TI  - Robust multispectral transparency in continuous metal film structures via
      multiple near-field plasmon coupling by a finite-difference time-domain method.
AB  - We propose a robust multispectral transparent plasmonic structure and calculate
      its transparency response by using the three-dimensional finite-difference time
      domain (FDTD) method. The proposed structure is composed of a continuous
      ultrathin metal film sandwiched by double two-dimensional (2D) hexagonal non
      close-packed metal-dielectric multilayer core-shell nanoparticle arrays. The top
      and bottom plasmonic arrays in such a structure, respectively, act as the light
      input and output couplers to carry out the efficient trapping and release of
      light. Near-perfect multispectral optical transparency in the visible and near
      infrared regions is achieved theoretically. The calculated electric field
      distribution patterns show that the near-perfect multispectral optical
      transparency mainly originates from the excitation and hybridization of shell and
      core plasmon modes, strong near-field coupling of dipole plasmon modes between
      adjacent nanoparticles as well as the excitation of surface plasmon waves of the
      metal film. The robust transparency bands can be efficiently tuned in a large
      range by varying the structural parameters and the surrounding dielectric
      environment. The proposed structure also shows additional merits such as a deep
      sub-wavelength size and fully retained electrical and mechanical properties of
      the natural metal. These features might provide promising applications in highly
      integrated optoelectronic devices including plasmonic filters, nanoscale
      multiplexers, and non-linear optics. 

PMID- 24452787
TI  - E-cigarettes cause indoor air pollution and inflammation, German study shows.

PMID- 24452788
TI  - Disseminated histoplasmosis (Histoplasma capsulatum) in a pet rabbit: case report
      and review of the literature.
AB  - A 2.5-year-old intact male miniature lop rabbit (Oryctolagus cuniculus) was
      presented with multiple nodules surrounding the eyes, nose, mouth, and prepuce.
      Cytological evaluation of the periocular nodules revealed the presence of
      intracellular (within macrophages) and extracellular yeast organisms. The yeast
      organisms were approximately 3-5 um in diameter, round to oval, with a thin clear
      capsule, and contained an eccentrically placed basophilic crescent-shaped
      nucleus. The clinical pathological interpretation was granulomatous inflammation
      with intralesional yeast of a morphology consistent with Histoplasma spp. The
      rabbit was treated with microsized griseofulvin (25 mg/kg, orally, once a day)
      for 12 days pending final cytological diagnosis of histoplasmosis. No significant
      improvement was noted during the treatment period, and humane euthanasia was
      performed. Postmortem examination revealed the presence of intracellular and
      extracellular yeast organisms in the small intestine, skin (antebrachium,
      perioral, palpebral, perianal, and pinnal), penis, penile urethra, rectum,
      axillary lymph node, and conjunctiva. Postmortem fungal culture yielded
      Histoplasma capsulatum. Based on clinical and postmortem findings, a definitive
      diagnosis of disseminated histoplasmosis was made. Disseminated histoplasmosis
      appears to be unreported in rabbits. Although the treatment used did not provide
      noticeable improvement, available information on histoplasmosis treatment in
      other species has been reviewed to provide useful information for future
      management of this condition in rabbits. 

PMID- 24452789
TI  - Safely assessing radiofrequency heating potential of conductive devices using
      image-based current measurements.
AB  - PURPOSE: Many procedures involving catheters and implanted medical devices could
      benefit from MRI guidance but are currently contraindicated due to risk of
      significant heating near linear conductive structures. A priori safety prediction
      is impossible in vivo and thus, safety is typically investigated in vitro by
      directly measuring temperature rise. Existing methods of investigating safety are
      inflexible and provide few data. Furthermore, they are fundamentally limited
      because dangerous temperatures rises can only be investigated if induced. A
      method of remotely predicting safety is necessary for ensuring safety in
      patients. THEORY AND METHODS: Electric current induced on the metallic object
      causes any dangerous heating; thus a remote method of safely characterizing the
      induced radiofrequency (RF) current distribution would suffice to evaluate safety
      assuming conservative estimates for local tissue properties. Here we propose a
      method of analyzing induced phase artifacts seen in low-specific absorption rate
      characterization images, to determine induced current on an interventional
      device. This induced current distribution can then be used to predict RF heating
      behavior under application of any other imaging sequence. RESULTS: This method
      has been successfully used to reproduce numerical simulations in a phantom.
      Furthermore, the heating behavior around a conductive wire produced by a scan
      other than that used to characterize current was successfully predicted.
      CONCLUSION: It has been shown in phantom experiments that remote current
      characterization can safely prevent dangerous scans as well as enable safe scans
      that previously would not have been attempted.

PMID- 24452790
TI  - FOXM1c promotes pancreatic cancer epithelial-to-mesenchymal transition and
      metastasis via upregulation of expression of the urokinase plasminogen activator
      system.
AB  - PURPOSE: The transcription factor Forkhead box M1 (FOXM1) plays important roles
      in the formation of several human tumors, including pancreatic cancer. However,
      the molecular mechanisms by which FOXM1 promotes pancreatic tumor epithelial-to
      mesenchymal transition (EMT) and metastasis are unknown. EXPERIMENTAL DESIGN: The
      effect of altered expression of FOXM1 and urokinase-type plasminogen activator
      receptor (uPAR) on EMT and metastasis was examined using animal models of
      pancreatic cancer. Also, the underlying mechanisms of altered pancreatic cancer
      invasion and metastasis were analyzed using in vitro molecular biology assays.
      Finally, the clinical relevance of dysregulated FOXM1/uPAR signaling was
      investigated using pancreatic tumor and normal pancreatic tissue specimens.
      RESULTS: Pancreatic tumor specimens and cell lines predominantly overexpressed
      the FOXM1 isoform FOXM1c. FOXM1c overexpression promoted EMT in and migration,
      invasion, and metastasis of pancreatic cancer cells, whereas downregulation of
      FOXM1 expression inhibited these processes. The level of FOXM1 expression
      correlated directly with that of uPAR expression in pancreatic cancer cell lines
      and tumor specimens. Moreover, FOXM1c overexpression upregulated uPAR expression
      in pancreatic cancer cells, whereas inhibition of FOXM1 expression suppressed
      uPAR expression. Furthermore, transfection of FOXM1c into pancreatic cancer cells
      directly activated the uPAR promoter, whereas inhibition of FOXM1 expression by
      FOXM1 siRNA suppressed its activation in these cells. Finally, we identified an
      FOXM1-binding site in the uPAR promoter and demonstrated that FOXM1 protein bound
      directly to it. Deletion mutation of this site significantly attenuated uPAR
      promoter activity. CONCLUSIONS: Our findings demonstrated that FOXM1c contributes
      to pancreatic cancer development and progression by enhancing uPAR gene
      transcription, and thus, tumor EMT and metastasis.

PMID- 24452791
TI  - Improved recurrence-free survival with ARCON for anemic patients with laryngeal
      cancer.
AB  - PURPOSE: Anemia is associated with poor tumor control. It was previously observed
      that accelerated radiotherapy combined with carbogen breathing and nicotinamide
      (ARCON) can correct this adverse outcome in patients with head and neck cancer.
      The purpose of this study was to validate this observation based on data from a
      randomized trial. EXPERIMENTAL DESIGN: Of 345 patients with cT2-4 laryngeal
      cancer, 174 were randomly assigned to accelerated radiotherapy and 171 to ARCON.
      Hemoglobin levels, measured before treatment, were defined as low when <7.5
      mmol/L for women and <8.5 mmol/L for men. The hypoxia marker pimonidazole was
      used to assess the oxygenation status in tumor biopsies. Data were analyzed 2
      years after inclusion of the last patient. RESULTS: Pretreatment hemoglobin
      levels were available and below normal in 27 of 173 (16%) accelerated
      radiotherapy and 27 of 167 (16%) ARCON patients. In patients with normal
      pretreatment, hemoglobin levels treatment with ARCON had no significant effect on
      5-year loco-regional control (LRC, 79% versus 75%; P = 0.44) and disease-free
      survival (DFS, 75% vs. 70%; P = 0.46) compared with accelerated radiotherapy.
      However, in patients with low pretreatment, hemoglobin levels ARCON significantly
      improved 5-year LRC (79% vs. 53%; P = 0.03) and DFS (68% vs. 45%; P = 0.04). In
      multivariate analysis including other prognostic factors, pretreatment hemoglobin
      remained prognostic for LRC and DFS in the accelerated radiotherapy treatment
      arm. No correlation between pretreatment hemoglobin levels and pimonidazole
      uptake was observed. CONCLUSION: Results from the randomized phase III trial
      support previous observations that ARCON has the potential to correct the poor
      outcome of cancer patients with anemia (ClinicalTrials.gov number, NCT00147732).

PMID- 24452792
TI  - Giants in orthopaedic surgery: Jacquelin Perry MD, DSc (Hon).

PMID- 24452793
TI  - Managing acetabular fractures in the elderly with fixation and primary
      arthroplasty: aiming for early weightbearing.
AB  - BACKGROUND: Osteoporotic acetabular fractures in the elderly are becoming more
      common. Regardless of treatment, most patients are managed with a period of
      protected weightbearing, even if a THA has been performed. We have tried to treat
      these patients analogously to geriatric femoral neck fractures in a way that
      allows immediate full weightbearing. QUESTIONS/PURPOSES: We determined return to
      mobility, length of hospital stay (LOS), radiographic outcomes, and complications
      in a series of elderly osteoporotic patients treated for acetabular fractures
      with early fracture fixation and simultaneous THA, allowing full weightbearing
      immediately postoperatively. METHODS: Since 2009, one surgeon (MR) used a
      consistent approach for fracture fixation and THA with immediate weightbearing in
      all patients older than 65 years with acetabular fractures who were fit for
      surgery and whose injuries were deemed osteoporotic fractures (low-energy
      mechanisms) meeting particular radiographic criteria (significant marginal
      impaction or femoral head damage). Twenty-four patients met these criteria and
      were reviewed at a mean of 24 months (range, 8-38 months). Mean age was 77 years
      (range, 63-90 years), and eight patients were women. The surgical technique
      included plate stabilization of both acetabular columns plus simultaneous THA
      using a tantalum socket and a cemented femoral stem. Clinical and note reviews
      were conducted to ascertain return to mobility, LOS, and postoperative
      complications. Component migration and fracture healing were assessed on plain
      radiographs. RESULTS: All patients mobilized with full weightbearing by Day 7
      postoperatively. Only one patient remained dependent on a frame to mobilize at
      discharge. At 6 weeks, two patients already required no walking aids. At 6
      months, patients were using a single stick at home at most, and all patients had
      managed stairs. Mean LOS was 18 days (range, 10-36 days). Radiographically, no
      component migration was seen in any patient. Seventeen of 24 fractures (71%)
      healed radiographically by 12 weeks, and all healed by 6 months. We recorded one
      superficial wound infection, one symptomatic deep venous thrombosis, and one in
      hospital death from myocardial infarction. CONCLUSIONS: Selected older patients
      with acetabular fractures may be managed using immediate weightbearing after
      fracture fixation and THA. However, this surgery is complex and requires a mixed
      skill set. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 24452794
TI  - Is there a difference in sagittal alignment of Blount's disease between
      radiographic and clinical evaluation?
AB  - BACKGROUND: A procurvatum deformity of the proximal tibia often is seen in
      patients with Blount's disease. If left untreated, it can lead to progressive
      angulation in the sagittal plane and altered contact stresses across the knee.
      QUESTIONS/PURPOSES: We asked the following questions: (1) Is the mean angle of
      procurvatum measured from full-length lateral radiographs of the tibia greater
      than that of procurvatum measured from clinical photographs of the affected lower
      extremity? (2) Is there a linear relationship between radiographically measured
      procurvatum and radiographically measured procurvatum? METHODS: We treated 72
      patients surgically for Blount's disease between 1997 and 2012; of those, 29
      patients were excluded from this analysis because they did not have adequate
      photographs or radiographs, leaving 43 patients (60% of the patients treated
      surgically; 47 limbs total), mean age of 13 years (range, 6-25 years), who
      underwent surgical realignment for Blount's disease were retrospectively
      evaluated at a median of 97 months after surgery (range, 24-170 months). Genu
      procurvatum was measured from full-length lateral radiographs of the tibia and
      clinical photographs of the affected lower extremity. We then assessed the
      relationship between radiographically measured procurvatum and clinically
      measured procurvatum using linear regression analysis. RESULTS: The mean
      preoperative radiographically measured procurvatum (12.3 degrees ; range -3.1
      degrees  to 55.2 degrees ) was larger than the clinically measured procurvatum
      (6.0 degrees ; range, -1 degrees  to 45 degrees ; p = 0.024). The mean
      postoperative radiographically measured procurvatum (4.2 degrees ; range -4.8
      degrees  to 30.3 degrees ) was larger than the clinically measured procurvatum
      (2.1 degrees ; range, -2 degrees  to 20 degrees ; p = 0.041). Preoperatively and
      postoperatively, radiographically measured procurvatum and clinically measured
      procurvatum were well correlated (linear regression p < 0.001). After surgical
      realignment, the mean improvement in radiographically measured procurvatum (8.2
      degrees ) was larger than that measured for clinically measured procurvatum (3.8
      degrees ) (p = 0.018). CONCLUSIONS: In patients with Blount's disease, visual
      inspection of the extremity can underestimate the procurvatum deformity of the
      proximal tibia relative to the measurable deformity on radiographs. Furthermore,
      surgical correction of proximal tibial procurvatum does not lead to clinical
      hyperextension of the knee. LEVEL OF EVIDENCE: Level IV, diagnostic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 24452795
TI  - A novel closed reduction with extension block and flexion block using Kirschner
      wires and microscrew fixation for mallet fractures.
AB  - BACKGROUND: Some patients with mallet fractures who undergo extension block
      pinning complain of exposed wires, which delay their return to sports and causes
      inconvenience while performing tasks that require the use of hands during the
      early postoperative period. The purpose of this retrospective study was to
      present and evaluate a novel surgical procedure for mallet fractures. METHODS: We
      treated 20 patients (14 males and six females; mean age, 38.4 years; range 17-68
      years) with displaced mallet fractures involving >30 % of the articular surface
      using the closed reduction and microscrew fixation between January 2009 and
      January 2012. The distal interphalangeal joint (DIP) joint was immobilized with a
      splint for 1-3 weeks on an individual case basis. According to Wehbe and
      Schneider's classification, there were 12 type IB, six type IIB, and two type IA
      fractures. The mean follow-up duration was 12.6 months (range 6-31 months).
      RESULTS: Bone union was achieved in all patients within a mean period of 6.8
      weeks, with no incidence of infection, skin necrosis, permanent nail deformity,
      or secondary osteoarthritis. Only two complications-temporary nail ridging in one
      patient and a dorsal bump caused by the screw in one patient-were observed.
      Minimum postoperative displacement was observed in one patient, for whom
      immobilization with a splint was continued for 4 weeks. Articular incongruity was
      <1.0 mm in four patients and 1.0-2.0 mm in two patients. Mean DIP joint extension
      loss was 6.5 degrees  and mean flexion was 67.8 degrees . The surgical outcomes
      were excellent in seven patients, good in nine, and fair in four according to
      Crawford's evaluation criteria. CONCLUSION: Our novel surgical procedure
      combining closed reduction with extension block and flexion block using Kirschner
      wires and microscrew fixation produces good clinical results with relatively few
      complications.

PMID- 24452796
TI  - A ribozyme that triphosphorylates RNA 5'-hydroxyl groups.
AB  - The RNA world hypothesis describes a stage in the early evolution of life in
      which RNA served as genome and as the only genome-encoded catalyst. To test
      whether RNA world organisms could have used cyclic trimetaphosphate as an energy
      source, we developed an in vitro selection strategy for isolating ribozymes that
      catalyze the triphosphorylation of RNA 5'-hydroxyl groups with trimetaphosphate.
      Several active sequences were isolated, and one ribozyme was analyzed in more
      detail. The ribozyme was truncated to 96 nt, while retaining full activity. It
      was converted to a trans-format and reacted with rates of 0.16 min(-1) under
      optimal conditions. The secondary structure appears to contain a four-helical
      junction motif. This study showed that ribozymes can use trimetaphosphate to
      triphosphorylate RNA 5'-hydroxyl groups and suggested that RNA world organisms
      could have used trimetaphosphate as their energy source. 

PMID- 24452797
TI  - Super-resolution optical DNA Mapping via DNA methyltransferase-directed click
      chemistry.
AB  - We demonstrate an approach to optical DNA mapping, which enables near single
      molecule characterization of whole bacteriophage genomes. Our approach uses a DNA
      methyltransferase enzyme to target labelling to specific sites and copper
      catalysed azide-alkyne cycloaddition to couple a fluorophore to the DNA. We
      achieve a labelling efficiency of ~70% with an average labelling density
      approaching one site every 500 bp. Such labelling density bridges the gap between
      the output of a typical DNA sequencing experiment and the long-range information
      derived from traditional optical DNA mapping. We lay the foundations for a wider
      scale adoption of DNA mapping by screening 11 methyltransferases for their
      ability to direct sequence-specific DNA transalkylation; the first step of the
      DNA labelling process and by optimizing reaction conditions for fluorophore
      coupling via a click reaction. Three of 11 enzymes transalkylate DNA with the
      cofactor we tested (a readily prepared s-adenosyl-l-methionine analogue). 

PMID- 24452798
TI  - Purification, characterization and crystallization of the human 80S ribosome.
AB  - Ribosomes are key macromolecular protein synthesis machineries in the cell. Human
      ribosomes have so far not been studied to atomic resolution because of their
      particularly complex structure as compared with other eukaryotic or prokaryotic
      ribosomes, and they are difficult to prepare to high homogeneity, which is a key
      requisite for high-resolution structural work. We established a purification
      protocol for human 80S ribosomes isolated from HeLa cells that allows obtaining
      large quantities of homogenous samples as characterized by biophysical methods
      using analytical ultracentrifugation and multiangle laser light scattering.
      Samples prepared under different conditions were characterized by direct single
      particle imaging using cryo electron microscopy, which helped optimizing the
      preparation protocol. From a small data set, a 3D reconstruction at subnanometric
      resolution was obtained showing all prominent structural features of the human
      ribosome, and revealing a salt concentration dependence of the presence of the
      exit site tRNA, which we show is critical for obtaining crystals. With these well
      characterized samples first human 80S ribosome crystals were obtained from
      several crystallization conditions in capillaries and sitting drops, which
      diffract to 26 A resolution at cryo temperatures and for which the
      crystallographic parameters were determined, paving the way for future high
      resolution work. 

PMID- 24452799
TI  - Adjacent single-stranded regions mediate processing of tRNA precursors by RNase E
      direct entry.
AB  - The RNase E family is renowned for being central to the processing and decay of
      all types of RNA in many species of bacteria, as well as providing the first
      examples of endonucleases that can recognize 5'-monophosphorylated ends thereby
      increasing the efficiency of cleavage. However, there is increasing evidence that
      some transcripts can be cleaved efficiently by Escherichia coli RNase E via
      direct entry, i.e. in the absence of the recognition of a 5'-monophosphorylated
      end. Here, we provide biochemical evidence that direct entry is central to the
      processing of transfer RNA (tRNA) in E. coli, one of the core functions of RNase
      E, and show that it is mediated by specific unpaired regions that are adjacent,
      but not contiguous to segments cleaved by RNase E. In addition, we find that
      direct entry at a site on the 5' side of a tRNA precursor triggers a series of 5'
      monophosphate-dependent cleavages. Consistent with a major role for direct entry
      in tRNA processing, we provide additional evidence that a 5'-monophosphate is not
      required to activate the catalysis step in cleavage. Other examples of tRNA
      precursors processed via direct entry are also provided. Thus, it appears
      increasingly that direct entry by RNase E has a major role in bacterial RNA
      metabolism. 

PMID- 24452800
TI  - Distinct functions of the RNA polymerase sigma subunit region 3.2 in RNA priming
      and promoter escape.
AB  - The sigma subunit of bacterial RNA polymerase (RNAP) has been implicated in all
      steps of transcription initiation, including promoter recognition and opening,
      priming of RNA synthesis, abortive initiation and promoter escape. The post
      promoter-recognition sigma functions were proposed to depend on its conserved
      region sigma3.2 that directly contacts promoter DNA immediately upstream of the
      RNAP active centre and occupies the RNA exit path. Analysis of the transcription
      effects of substitutions and deletions in this region in Escherichia coli
      sigma(70) subunit, performed in this work, suggests that (i) individual residues
      in the sigma3.2 finger collectively contribute to RNA priming by RNAP, likely by
      the positioning of the template DNA strand in the active centre, but are not
      critical to promoter escape; (ii) the physical presence of sigma3.2 in the RNA
      exit channel is important for promoter escape; (iii) sigma3.2 promotes sigma
      dissociation during initiation and suppresses sigma-dependent promoter-proximal
      pausing; (iv) sigma3.2 contributes to allosteric inhibition of the initiating NTP
      binding by rifamycins. Thus, region sigma3.2 performs distinct functions in
      transcription initiation and its inhibition by antibiotics. The B-reader element
      of eukaryotic factor TFIIB likely plays similar roles in RNAPII transcription,
      revealing common principles in transcription initiation in various domains of
      life. 

PMID- 24452801
TI  - Transcriptome-wide investigation of genomic imprinting in chicken.
AB  - Genomic imprinting is an epigenetic mechanism by which alleles of some specific
      genes are expressed in a parent-of-origin manner. It has been observed in mammals
      and marsupials, but not in birds. Until now, only a few genes orthologous to
      mammalian imprinted ones have been analyzed in chicken and did not demonstrate
      any evidence of imprinting in this species. However, several published
      observations such as imprinted-like QTL in poultry or reciprocal effects keep the
      question open. Our main objective was thus to screen the entire chicken genome
      for parental-allele-specific differential expression on whole embryonic
      transcriptomes, using high-throughput sequencing. To identify the parental origin
      of each observed haplotype, two chicken experimental populations were used, as
      inbred and as genetically distant as possible. Two families were produced from
      two reciprocal crosses. Transcripts from 20 embryos were sequenced using NGS
      technology, producing ~200 Gb of sequences. This allowed the detection of 79
      potentially imprinted SNPs, through an analysis method that we validated by
      detecting imprinting from mouse data already published. However, out of 23
      candidates tested by pyrosequencing, none could be confirmed. These results come
      together, without a priori, with previous statements and phylogenetic
      considerations assessing the absence of genomic imprinting in chicken. 

PMID- 24452802
TI  - Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA
      precursors.
AB  - Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with
      let-7 precursors. Previous studies have described seemingly inconsistent Lin28
      binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the
      binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using
      biochemical and biophysical methods. First, we investigate Lin28 binding to TL
      let-7g variants and short RNA fragments and identify three independent binding
      sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a
      stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold
      shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of
      TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28
      to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal
      loop of pre-let-7g extends to other precursors of the let-7 family, but not to
      other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2
      and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let
      7 is required for maximum inhibition of Dicer cleavage for a least one member of
      the let-7 family and may be important for orchestrating the activity of the
      several factors that regulate let-7 biogenesis. 

PMID- 24452803
TI  - Expanding the zinc-finger recombinase repertoire: directed evolution and
      mutational analysis of serine recombinase specificity determinants.
AB  - The serine recombinases are a diverse family of modular enzymes that promote high
      fidelity DNA rearrangements between specific target sites. Replacement of their
      native DNA-binding domains with custom-designed Cys2-His2 zinc-finger proteins
      results in the creation of engineered zinc-finger recombinases (ZFRs) capable of
      achieving targeted genetic modifications. The flexibility afforded by zinc-finger
      domains enables the design of hybrid recombinases that recognize a wide variety
      of potential target sites; however, this technology remains constrained by the
      strict recognition specificities imposed by the ZFR catalytic domains. In
      particular, the ability to fully reprogram serine recombinase catalytic
      specificity has been impeded by conserved base requirements within each
      recombinase target site and an incomplete understanding of the factors governing
      DNA recognition. Here we describe an approach to complement the targeting
      capacity of ZFRs. Using directed evolution, we isolated mutants of the beta and
      Sin recombinases that specifically recognize target sites previously outside the
      scope of ZFRs. Additionally, we developed a genetic screen to determine the
      specific base requirements for site-specific recombination and showed that
      specificity profiling enables the discovery of unique genomic ZFR substrates.
      Finally, we conducted an extensive and family-wide mutational analysis of the
      serine recombinase DNA-binding arm region and uncovered a diverse network of
      residues that confer target specificity. These results demonstrate that the ZFR
      repertoire is extensible and highlights the potential of ZFRs as a class of
      flexible tools for targeted genome engineering.

PMID- 24452804
TI  - Rational optimization of tolC as a powerful dual selectable marker for genome
      engineering.
AB  - Selection has been invaluable for genetic manipulation, although counter
      selection has historically exhibited limited robustness and convenience. TolC, an
      outer membrane pore involved in transmembrane transport in E. coli, has been
      implemented as a selectable/counter-selectable marker, but counter-selection
      escape frequency using colicin E1 precludes using tolC for inefficient genetic
      manipulations and/or with large libraries. Here, we leveraged unbiased deep
      sequencing of 96 independent lineages exhibiting counter-selection escape to
      identify loss-of-function mutations, which offered mechanistic insight and guided
      strain engineering to reduce counter-selection escape frequency by ~40-fold. We
      fundamentally improved the tolC counter-selection by supplementing a second
      agent, vancomycin, which reduces counter-selection escape by 425-fold, compared
      colicin E1 alone. Combining these improvements in a mismatch repair proficient
      strain reduced counter-selection escape frequency by 1.3E6-fold in total, making
      tolC counter-selection as effective as most selectable markers, and adding a
      valuable tool to the genome editing toolbox. These improvements permitted us to
      perform stable and continuous rounds of selection/counter-selection using tolC,
      enabling replacement of 10 alleles without requiring genotypic screening for the
      first time. Finally, we combined these advances to create an optimized E. coli
      strain for genome engineering that is ~10-fold more efficient at achieving
      allelic diversity than previous best practices. 

PMID- 24452805
TI  - Effects of cardiac rehabilitation in diabetic patients: both cardiac and
      noncardiac factors determine improvement in exercise capacity.
AB  - BACKGROUND: Diabetic patients have a worse prognosis than nondiabetic patients
      after myocardial infarction. Although exercise improves risk factors, exercise
      capacity, and mortality, it is still unclear if these benefits are the same as in
      nondiabetics. Furthermore, although exercise tolerance is predicted by systolic
      and diastolic dysfunction in nondiabetics, its role as a predictor of exercise
      capacity in diabetics remains unclear. HYPOTHESIS: Diabetics and nondiabetics see
      a similar improvement in their cardiac risk factors and exercise parameters from
      exercise-based cardiac rehabilitation (CR). METHODS: A series of 370 diabetics
      and 942 nondiabetics entered a 36-session outpatient CR program after
      interventions for coronary heart disease or after bypass or cardiac valve
      surgery. The program consisted of physical exercise, lifestyle modification, and
      pharmacotherapy. RESULTS: Quality of life, weight, blood pressure, and lipid
      profiles improved significantly in both groups during the 12-week program.
      Baseline metabolic equivalents (METs) were lower in diabetics vs nondiabetics at
      the start of CR (2.4 vs 2.7, P < 0.001). Although both groups increased their
      exercise capacity, diabetics had less improvement (change in METs 1.7 vs 2.6, P <
      0.001). Significant predictors for improvement after CR included age, sex, and
      weight, as well as both systolic and diastolic function. After adjustment for
      these, diabetes remained a significant predictor of reduced improvement in
      exercise capacity. CONCLUSIONS: Diabetics saw a significant benefit in quality of
      life, weight, exercise tolerance, and cardiac risk factors, but to a lesser
      extent when compared with nondiabetics. The mechanisms for poorer improvement in
      diabetics following CR also include noncardiac factors and require further study.

PMID- 24452806
TI  - Genetic analysis of the 9p21.3 CAD risk locus in Asian Indians.
AB  - The 9p21.3 locus is the best replicated region to date for coronary artery
      disease (CAD). We investigated the association of 9p21.3 common variants with
      CAD, candidate gene expression including ANRIL, a non-coding RNA, followed by in
      vitro validation. Five variants, rs10757278, rs10757274, rs2383206, rs1333049 and
      rs4977574 were genotyped in 1,034 cases and 1,034 controls. Gene expression of
      C9orf5, MTAP1, MTAP 2, p16INK4a, p14ARF, p15INK4b and two ANRIL splice variants,
      NR_003529 and EU741058, were measured in 100 cases and 100 controls. Human aortic
      smooth muscle cells (HuAoSMCs) were transfected with siRNA targeting ANRIL exon
      19 (siRNA-1) or exon 2 (siRNA-2) and consequent effect determined. rs2383206
      showed the highest association with CAD (odds ratio [OR] 2.02, 95% confidence
      interval [CI] 1.56 -2.62) and an adjusted OR of 2.55, 1.33-2.88 along with
      rs10757278. Conventional risk factors (conventional RFs), rs2383206 and
      rs10757278 variants together yielded a higher c index (OR 0.790, 95% CI 0.770 
      0.810) as compared to conventional RFs (OR 0.783, 95% CI 0.763-0.803) or genetic
      variants (OR 0.561, 95% CI 0.536-0.586) alone. GAAAA haplotype showed significant
      protective association with CAD compared to CGGGG risk haplotype (OR 0.45, 95% CI
      0.27-0.77). Expression of p16INK4a, p14ARF and p15INK4b as well as plasma CDKN2A
      levels were lower in cases than controls. GG genotype was associated with higher
      EU741058 expression and lower p16INK4a expression. HuAoSMCs transfected with
      siRNA-1 showed lower NR_003529, p16INK4aand p14ARFexpression. Our study provides
      further evidence on the significance of 9p21.3 locus for CAD wherein the risk
      allele regulate the expression of ANRIL and adjacent tumour suppressor genes
      which in turn alter smooth muscle proliferation, a fundamental process in
      atherosclerosis. 

PMID- 24452807
TI  - Concentration dependency in nicotine skin penetration flux from aqueous solutions
      reflects vehicle induced changes in nicotine stratum corneum retention.
AB  - PURPOSE: This study sought to understand the mechanism by which the steady state
      flux of nicotine across the human skin from aqueous solutions is markedly
      decreased at higher nicotine concentrations. METHODS: Nicotine's steady state
      flux through human epidermis and its amount in the stratum corneum for a range of
      aqueous nicotine solutions was determined using Franz diffusion cells, with the
      nicotine analysed by high performance liquid chromatography (HPLC). Nicotine's
      thermodynamic activity in the various solutions was estimated from its partial
      vapour pressure and stratum corneum hydration was determined using a corneometer.
      The amount of nicotine retained in the stratum corneum was estimated from the
      nicotine amount found in individual stratum corneum tape strips and a D-Squame
      determined weight for each strip. RESULTS: The observed steady state flux of
      nicotine across human epidermis was found to show a parabolic dependence on
      nicotine concentration, with the flux proportional to its thermodynamic activity
      up to a concentration of 48% w/w. The nicotine retention in the stratum corneum
      showed a similar dependency on concentration whereas the diffusivity of nicotine
      in the stratum corneum appeared to be concentration independent. This retention,
      in turn, could be estimated from the extent of stratum corneum hydration and the
      nicotine concentration in the applied solution and volume of water in the skin.
      CONCLUSIONS: Nonlinear dependency of nicotine skin flux on its concentration
      results from a dehydration induced decrease in its stratum corneum retention at
      higher concentration and not dehydration induced changes nicotine diffusivity in
      the stratum corneum.

PMID- 24452809
TI  - Population pharmacokinetic modelling of recombinant factor IX Fc fusion protein
      (rFIXFc) in patients with haemophilia B.
AB  - BACKGROUND AND OBJECTIVES: Recombinant factor IX Fc fusion protein (rFIXFc) is a
      clotting factor developed using monomeric Fc fusion technology to prolong the
      circulating half-life of factor IX. The objective of this analysis was to
      elucidate the pharmacokinetic characteristics of rFIXFc in patients with
      haemophilia B and identify covariates that affect rFIXFc disposition. METHODS:
      Population pharmacokinetic analysis using NONMEM((r)) was performed with clinical
      data from two completed trials in previously treated patients with severe to
      moderate haemophilia B. Twelve patients from a phase 1/2a study and 123 patients
      from a registrational phase 3 study were included in this population analysis.
      RESULTS: A three-compartment model was found to best describe the
      pharmacokinetics of rFIXFc. For a typical 73 kg patient, the clearance (CL),
      volume of the central compartment (V 1) and volume of distribution at steady
      state (V ss) were 2.39 dL/h, 71.4 dL and 198 dL, respectively. Because of repeat
      pharmacokinetic profiles at week 26 for patients in a subgroup, inclusion of
      inter-occasion variability (IOV) on CL and V 1 were evaluated and significantly
      improved the model. The magnitude of IOV on CL and V 1 were both low to moderate
      (<20 %) and less than the corresponding inter-individual variability. Body weight
      (BW) was found to be the only significant covariate for rFIXFc disposition.
      However, the impact of BW was limited, as the BW power exponents on CL and V 1
      were 0.436 and 0.396, respectively. CONCLUSION: This is the first population
      pharmacokinetic analysis that systematically characterized the pharmacokinetics
      of long-lasting rFIXFc in patients with haemophilia B. The population
      pharmacokinetic model for rFIXFc can be utilized to evaluate and optimize dosing
      regimens for the treatment of patients with haemophilia B.

PMID- 24452808
TI  - Encapsulation of poorly soluble drugs in polymer-drug conjugates: effect of dual
      drug nanoformulations on cancer therapy.
AB  - PURPOSE: Current cancer chemotherapy is gradually shifting to the application of
      drug combinations that prevent development of drug resistance. Many anticancer
      drugs have poor solubility and limited oral bioavailability. Using an innovative
      approach, we developed dual-drug nanoformulations of a polymeric nanogel
      conjugate with anticancer 5-FU nucleoside analog, floxuridine (FLOX), and the
      second anticancer drugs, paclitaxel (PCL), or a geldanamycin analog, 17-AAG, for
      combination therapy. METHODS: PCL or 17-AAG had been encapsulated in the
      cholesteryl-polyvinyl alcohol-floxuridine nanogel (CPVA-FLOX) by simple solution
      mixing and sonication. Dual nanodrugs formed particles with diameter 180 nm and
      either drug content (5-20%) that were stable and could be administered orally.
      Their cytotoxicity in human and mouse cancer cells was determined by MTT assay,
      and cellular target inhibition - by Western blot analysis. Tumor growth
      inhibition was evaluated using an orthotopic mouse mammary 4T1 cancer model.
      RESULTS: CPVA-FLOX was more potent than free drug in cancer models including drug
      resistant ones; while dual nanodrugs demonstrated a significant synergy (CPVA
      FLOX/PCL), or showed no significant synergy (CPVA-FLOX/17-AAG) compared to free
      drugs (PCL or 17-AAG). Dual nanodrug CPVA-FLOX/17-AAG effect on its cellular
      target (HSP70) was similar to 17-AAG alone. In animal model, however, both dual
      nanodrugs effectively inhibited tumor growth compared to CPVA-FLOX after oral
      administration. CONCLUSION: Oral dual-drug nanoformulations of poorly-soluble
      drugs proved to be a highly efficient combination anticancer therapy in
      preclinical studies.

PMID- 24452810
TI  - Population pharmacokinetic modeling of veliparib (ABT-888) in patients with non
      hematologic malignancies.
AB  - BACKGROUND AND OBJECTIVE: Veliparib (ABT-888) is a potent oral inhibitor of
      Poly(ADP-ribose) polymerase enzyme that is currently in development for the
      treatment of non-hematologic and hematologic malignancies. This analysis
      characterizes the population pharmacokinetics of veliparib, including developing
      a structural pharmacokinetic model and testing patient demographics and
      covariates for potential influence on veliparib pharmacokinetics in patients with
      non-hematologic malignancies. METHODS: The analysis dataset included 3,542
      veliparib concentration values from 325 patients with non-hematologic
      malignancies enrolled in three phase I and one phase II studies. Population
      pharmacokinetic modeling was performed using NONMEM. The likelihood ratio test
      was used for comparison of nested models, and visual predictive check was
      employed for model qualification. Covariates tested included body size measures,
      creatinine clearance (CLCR), formulation, age, sex, race, liver function tests,
      and coadministration with temozolomide. RESULTS: A one-compartment model with
      first-order absorption and elimination adequately described veliparib
      pharmacokinetics. The final model included fixed effects for CLCR on veliparib
      oral clearance (CL/F) and lean body mass (LBM) on volume of distribution (V d/F).
      CL/F and V d/F were 20.9 L/h (for a CLCR of 100 mL/min) and 173 L (for an LBM of
      56 kg), respectively. CONCLUSION: Only LBM and CLCR were found to be determinants
      of veliparib V d/F and CL/F, respectively. Dosage adjustments of veliparib on the
      basis of body size, age, sex, race, liver function, and temozolomide
      coadministration are not necessary in patients with non-hematologic malignancies.
      This is the first study to characterize the population pharmacokinetics of
      veliparib, and the developed model will be used to conduct simulations and
      evaluate veliparib exposure-response relationships.

PMID- 24452811
TI  - Role of microdialysis in pharmacokinetics and pharmacodynamics: current status
      and future directions.
AB  - Diagnostic and therapeutic decisions in medical practice are still generally
      based on blood concentrations of drugs and/or biomolecules despite the knowledge
      that biochemical events and pharmacological effects usually take place in tissue
      rather than in the bloodstream. Microdialysis is a semi-invasive technique that
      is able to measure concentrations of the free, active drug or endogenous
      compounds in almost all human tissues and organs. It is currently being used to
      monitor brain metabolic processes and quantify tissue biomarkers, and determine
      transdermal drug distribution and tissue pharmacokinetics, confirming its
      importance as a widely used sampling technique in clinical drug monitoring and
      drug development as well as therapy and disease follow-up, contributing to
      rationalizing drug dosing regimens and influencing the clinical decision-making
      process. 

PMID- 24452813
TI  - Optofluidic SERS chip with plasmonic nanoprobes self-aligned along microfluidic
      channels.
AB  - This work reports an optofluidic SERS chip with plasmonic nanoprobes self-aligned
      along microfluidic channels. Plasmonic nanoprobes with rich electromagnetic hot
      spots are selectively patterned along PDMS microfluidic channels by using a
      Scotch tape removal and oxygen plasma treatment, which also provide the permanent
      bonding between PDMS and a glass substrate. A silver film with an initial
      thickness of 30 nm after oxygen plasma treatment creates nanotips and nanodots
      with a maximum SERS performance, which were successfully implanted with
      microfluidic concentration gradient generators. The novel device enables the
      label-free and solution-phase SERS detection of small molecules with low Raman
      activity such as dopamine at micromolar level in flow. This optofluidic SERS chip
      can be readily expanded for microfluidic networks with diverse functions for
      advanced optical biochemical assays. 

PMID- 24452812
TI  - Survival benefit of CPAP favors hypercapnic patients with the overlap syndrome.
AB  - BACKGROUND: Patients with the combination of chronic obstructive pulmonary
      disease (COPD) and obstructive sleep apnea (OSA), known as the "overlap
      syndrome," have a substantially greater risk of morbidity and mortality compared
      to those with either COPD or OSA alone. The study's objective was to report on
      the long-term outcome of hypercapnic (PaCO2 >= 45 mmHg) and normocapnic patients
      with the overlap syndrome treated with continuous positive airway pressure
      (CPAP). METHODS: A nonconcurrent cohort of consecutive patients with the overlap
      syndrome was followed for a median duration of 71 months (range 1-100) at a VA
      sleep center. All patients were managed according to the prevailing
      recommendations of both diseases. The end point of the study was all-cause
      mortality. RESULTS: Of the 271 patients identified, 104 were hypercapnic (PaCO2 =
      51.6 +/- 4.3 mmHg). Both normocapnic and hypercapnic patients had comparable
      apnea-hypopnea indexes (AHI) (29.2 +/- 23.8 and 35.2 +/- 29.2/h, respectively; p
      = 0.07) and similar adherence rates to CPAP (43 and 42 %, respectively, p = 0.9).
      Survival analysis revealed that hypercapnic patients who were adherent to CPAP
      had reduced mortality compared to nonadherent hypercapnic patients (p = 0.04). In
      contrast, the cumulative mortality rate for normocapnic patients was not
      significantly different between the adherent and the nonadherent group (p =
      0.42). In multivariate analysis, the comorbidity index was the only independent
      predictor of mortality in normocapnic patients with the overlap syndrome [hazard
      ratio (HR) 1.68; p < 0.001] while CPAP adherence was associated with improved
      survival (HR 0.65; p = 0.04). CONCLUSIONS: CPAP mitigates the excess risk of
      mortality in hypercapnic patients but not in normocapnic patients with the
      overlap syndrome.

PMID- 24452814
TI  - Re-irradiation for painful heel spur syndrome. Retrospective analysis of 101
      heels.
AB  - PURPOSE: Painful heel spur syndrome is a common disease with a lifetime
      prevalence of approximately 10 %. One of the most effective treatment options is
      radiotherapy. Many authors recommend a second or third series of radiation for
      recurrent pain and partial or no response to the initial treatment. As the
      results of re-irradiation have not been systematically analyzed the aim of this
      study was to document the results of repeated radiation treatment and to identify
      patients who could benefit from this treatment. MATERIAL AND METHODS: The
      analysis was performed on patients from 2 German radiotherapy institutions and
      included 101 re-irradiated heels. Pain was documented with the numeric rating
      scale (NRS) and carried out before and directly after each radiation therapy as
      well as for the follow-up period of 24 months. The median age of the patients was
      56 years with 30.1 % male and 69.9 % female patients. Pain was caused by plantar
      fasciitis in 72.3 %, Haglund's exostosis in 15.8 % and Achilles tendinitis in
      11.9 %. Repeated radiation was indicated because the initial radiotherapy
      resulted in no response in 35.6 % of patients, partial response in 39.6 % and
      recurrent pain in 24.8 %. RESULTS: A significant response to re-irradiation could
      be found. For the whole sample the median NRS pain score was 6 before re
      irradiation, 2 after 6 weeks and 0 after 12 and 24 months. Of the patients 73.6 %
      were free of pain 24 months after re-irradiation. All subgroups, notably those
      with no response, partial response and recurrent pain had a significant reduction
      of pain. CONCLUSION: Re-irradiation of painful heel spur syndrome is an effective
      and safe treatment. All subgroups showed a good response to re-irradiation for at
      least 24 months.

PMID- 24452815
TI  - Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis
      (mouse) induced by fractionated irradiation.
AB  - BACKGROUND AND PURPOSE: Oral mucositis is a severe and dose limiting early side
      effect of radiotherapy for head-and-neck tumors. This study was initiated to
      determine the effect of bone marrow- and mesenchymal stem cell transplantation on
      oral mucositis (mouse tongue model) induced by fractionated irradiation. MATERIAL
      AND METHODS: Daily fractionated irradiation (5 * 3 Gy/week) was given over 1
      (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day
      7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to
      generate complete dose-effect curves. The incidence of mucosal ulceration,
      corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the
      primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were
      transplanted intravenously at various time points within these fractionation
      protocols. RESULTS: Transplantation of 6 * 10(6), but not of 3 * 10(6) bone
      marrow stem cells on day - 1, + 4, + 8, + 11 or + 15 significantly increased the
      ED50 values (dose, at which an ulcer is expected in 50 % of the mice);
      transplantation on day + 2, in contrast, was ineffective. Mesenchymal stem cell
      transplantation on day - 1, 2 or + 8 significantly, and on day + 4 marginally
      increased the ED50 values. CONCLUSION: Transplantation of bone marrow or
      mesenchymal stem cells has the potential to modulate radiation-induced oral
      mucositis during fractionated radiotherapy. The effect is dependent on the timing
      of the transplantation. The mechanisms require further investigation.

PMID- 24452816
TI  - Hippocampus sparing in whole-brain radiotherapy. A review.
AB  - Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not
      changed significantly since development of the procedure. However, the recent
      development of novel techniques such as intensity-modulated radiation therapy
      (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well
      as an increasing body of evidence concerning neural stem cells (NSCs) have
      altered the conventional WBRT treatment paradigm. In this regard, hippocampus
      sparing WBRT is a novel technique that aims to spare critical hippocampus regions
      without compromising tumour control. Published data on this new technique are
      limited to planning and feasibility studies; data on patient outcome are still
      lacking. However, several prospective trials to analyse the feasibility of this
      technique and to document clinical outcome in terms of reduced neurotoxicity are
      ongoing. 

PMID- 24452817
TI  - Temozolomide-induced liver damage. A case report.
AB  - BACKGROUND: Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy
      and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent
      glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed
      each year. Therefore, all severe side effects of TMZ, even those rarely observed,
      are relevant to radiotherapists. MATERIALS AND METHODS: We report a case of
      severe drug-induced toxic hepatitis that developed during chemoradiotherapy with
      TMZ in a patient with glioblastoma multiforme. RESULTS: Transaminase elevation
      was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms
      which only subsided 2 months later. These findings were consistent with diagnosis
      of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the
      early termination of treatment, no life-threatening complications occurred in our
      patient. However, rare reports of encephalopathy and fatality as complications of
      TMZ therapy can be found in the literature. CONCLUSION: When using TMZ for
      treatment of glioblastoma, monitoring of liver enzyme levels should be performed
      twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced
      hepatitis, TMZ must be discontinued immediately.

PMID- 24452818
TI  - Training staff to implement brief stimulus preference assessments.
AB  - We trained 9 behavioral staff members to conduct 2 brief preference assessments
      using 30-min video presentations that contained instructions and modeling. After
      training, we evaluated each staff member's implementation of the assessments in
      situ. Results indicated that 1 or 2 training sessions for each method were
      sufficient for teaching each staff member to implement each assessment. We
      briefly discuss the clinical implications of our findings. 

PMID- 24452819
TI  - Advantages of exercise in rehabilitation, treatment and prevention of altered
      morphological features in knee osteoarthritis. A narrative review.
AB  - Knee osteoarthritis (OA) represents one of the most common causes of disability
      in the world. It leads to social, psychological and economic costs with financial
      consequences, also because a further increase is expected. Different knee OA
      treatments are usually considered in relation to the stage of the disease, such
      as surgical management and pharmacologic and non-pharmacologic treatments.
      Treatment should begin with the safest and least invasive one, before proceeding
      to more invasive, expensive ones. Non-pharmacologic, behavioral treatments of
      knee OA are recommended not only in rehabilitation but also in prevention because
      many risk factors, such as excess weight, obesity and joint tissue inflammation,
      can be monitored and thus prevented. In the present review, we analyze data from
      the most recent literature in relation to the effects of physical exercise on
      prevention, therapy and rehabilitation in knee OA. All data suggest that physical
      exercise is an effective, economical and accessible tool to everyone, in the
      treatment and prevention of knee OA. The literature search was conducted on
      PubMed, Scopus and Google Scholar using appropriate keywords in relation to knee
      osteoarthritis.

PMID- 24452820
TI  - Cooperativity in beryllium bonds.
AB  - A theoretical study of the beryllium bonded clusters of the
      (iminomethyl)beryllium hydride and (iminomethyl)beryllium fluoride [HC(BeX)=NH, X
      = H, F] molecules has been carried out at the B3LYP/6-311++G(3df,2p) level of
      theory. Linear and cyclic clusters have been characterized up to the decamer. The
      geometric, energetic, electronic and NMR properties of the clusters clearly
      indicate positive cooperativity. The evolution of the molecular properties, as
      the size of the cluster increases, is similar to those reported in polymers held
      together by hydrogen bonds.

PMID- 24452821
TI  - Facile synthesis and characterization of polyethylenimine-coated Fe3O4
      superparamagnetic nanoparticles for cancer cell separation.
AB  - The detection of cancer cells in clinical samples is of great interest for a
      range of diagnostic applications, and separation and enrichment of cancer cells
      in low concentrations from complex sample matrices is necessary for efficient
      cancer diagnostics. In the present study, new surface-modified iron oxide
      nanoparticles were synthesized for the separation of lung cancer cells by simple
      precipitation of Fe(II) and Fe(III) salts in an aqueous ammonia solution,
      followed by the addition of polyethylenimine (PEI). The modified nanoparticles
      were characterized by X-ray diffractometry (XRD), transmission electron
      microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray
      photoelectron spectroscopy (XPS) and vibrating sample magnetometry (VSM). XRD and
      TEM revealed that the particles were ~10 nm in diameter, while FTIR and XPS
      showed that their surfaces were well coated with PEI. VSM results confirmed the
      superparamagnetic nature of PEI-coated Fe3O4 nanoparticles. The separation and
      enrichment of lung cancer cells from sputum samples was demonstrated using the
      synthesized developed PEI-coated Fe3O4 magnetic nanoparticles. Exfoliative
      cytopathology showed that the percentage of positive cells increased from 6.3%
      (38/600) in untreated sputum samples to 38.5% (231/600) in sputum samples treated
      with PEI-coated Fe3O4 magnetic nanocomposites. This finding indicated that PEI
      coated Fe3O4 magnetic nanocomposites can be used to efficiently enrich lung
      cancer cells from sputum for subsequent cytopathological analysis.

PMID- 24452822
TI  - Access to some NICE approved drugs varies hugely across England.

PMID- 24452823
TI  - Success of electrocardioversion on the elderly.
AB  - BACKGROUND: There are two treatment strategies for medication-resistant atrial
      fibrillation (AF): rhythm control or rate control. It has been suggested that
      rate control is a valid strategy in well-tolerated AF because it does not result
      in increased mortality. We aimed to investigate the 1-year outcome of rhythm
      control in an elderly population of AF patients. METHOD: The study was
      retrospective, using the data collected from electrocardioversions (ECV) of
      elderly patients and the data of their follow-up visits to the outpatient clinic.
      We looked for recurrence of AF within the first year after ECV. Furthermore, we
      investigated possible predictors of recurrence. RESULTS: From February 2008 till
      November 2011, 436 consecutive elderly patients admitted for ECV were included.
      The 1-year recurrence rate of AF was 51.3 %. We found that being female and a
      large left atrial diameter were independent predictors of recurrence. CONCLUSION:
      The AF recurrence rate in our elderly population is comparable with reported AF
      recurrence rates in a younger population; we conclude that rhythm control can be
      regarded as the viable strategy in persistent AF in elderly patients.

PMID- 24452824
TI  - Predictors of medication non-adherence in Bulgarian outpatients with
      schizophrenia.
AB  - The purpose of this study is to assess the adherence status and to identify the
      risk factors for medication non-adherence in Bulgarian outpatients with
      schizophrenia. Variables with possible impact on adherence behaviour were
      assessed via a set of pre-determined clinical interviews and self-rating scales
      in a total of 226 patients with schizophrenia. As non-adherent were classified
      55.8% of the participants. Differences between adherent and non-adherent patients
      were identified. A multiple regression analysis revealed three variables
      predictive for the medication adherence--attitudes toward medication, severity of
      positive symptoms and the ability to recognize psychotic symptoms. Interventions
      focusing on the identified predictive variables might be useful when aiming at
      improvement of medication adherence and outcome in schizophrenia.

PMID- 24452825
TI  - Effect of periodontal treatment on peak serum levels of inflammatory markers.
AB  - BACKGROUND AND OBJECTIVE: Some subjects with untreated periodontitis exhibit
      elevated levels of distinct inflammatory markers in serum. The aim of the study
      was to assess whether nonsurgical periodontal therapy changes the levels of these
      markers and lowers these peaks. METHODS: Forty periodontally diseased subjects
      received nonsurgical periodontal therapy (full-mouth scaling and root planing
      within 48 h) with either adjunctive systemic amoxicillin and metronidazole (n =
      19) or placebo (n = 21). Serum samples, obtained at baseline (BL) and 3 months
      after treatment (M3), were evaluated for 15 cytokines and 9 acute-phase proteins
      using the Bio-Plex bead array multianalyte detection system. For each analyte,
      peak values were defined as greater than the mean + 2 standard deviations (SD) of
      measurements found in 40 periodontally healthy persons. Proportions were compared
      using Fisher's exact test. RESULTS: At M3, a significantly better primary
      clinical outcome (persisting pockets of >4 mm with bleeding on probing) was
      obtained in patients treated with scaling and root planing plus antibiotics
      compared to those receiving placebo (3.3 +/- 5.1 vs. 6.8 +/- 7.8 pockets per
      patient, p < 0.05). The levels of cytokines and acute-phase proteins of
      periodontitis patients were usually below the mean + 2 SD threshold of healthy
      persons. However, values above threshold were found in some individuals. Eleven
      patients showed a peak value of one analyte, and seven patients showed two peaks.
      In the remaining 12 patients, between three and ten analytes showed peak values.
      Therapy greatly reduced the number of subjects with four or more peaks (BL, 11
      subjects; M3, 1 subject, p = 0.003). With regards to the reduction of peaks, no
      specific benefit of adjunctive antibiotics could be seen. CONCLUSION: Subjects
      with untreated periodontitis may show high peaks for several inflammatory markers
      in serum simultaneously. Nonsurgical periodontal treatment with or without
      antibiotics reduced most of these peak levels.

PMID- 24452826
TI  - The randomized shortened dental arch study: temporomandibular disorder pain.
AB  - OBJECTIVES: The aim of this multi-center, randomized controlled trial was to
      assess the impact of missing posterior support on the risk for temporomandibular
      disorder (TMD) pain by comparing patients with either shortened dental arches
      (SDA) or molar replacement by removable dental prostheses (RDP). METHODS: A
      sample of 215 patients with bilateral molar loss in at least one jaw was
      consecutively recruited in 14 prosthodontic departments of dental schools in
      Germany. Of the initial sample, 152 patients (mean age: 59.7 years; 53.9 %
      female) received randomly allocated interventions (SDA: n = 71; RDP: n = 81).
      Presence of TMD pain was assessed using patients' self-reports and was verified
      by physical examination and by pain intensity, as the mean of current pain, worst
      pain, and average pain in the last 6 months, with 10-point ordinal rating scales.
      Assessments were performed before treatment and at follow-ups until 60 months
      after treatment. Impact of interventions on TMD risk and pain intensity was
      computed by applying logistic and linear random-intercept models. RESULTS: Tooth
      replacement (RDP) did not significantly change the risk for self-reported (odds
      ratio [OR]: 1.1; confidence interval [CI]: 0.4 to 3.4) or clinically verified
      (OR: 0.7; CI: 0.1 to 4.3) TMD pain compared to no tooth replacement (SDA). Mean
      characteristic pain intensity was virtually identical in both groups (Coeff:
      0.01; CI: -0.30 to 0.32). CONCLUSION: Retaining or preservation of an SDA is not
      a major risk factor for TMD pain over the course of 5 years when compared to
      molar replacement with RPDs. CLINICAL RELEVANCE: Seemingly, missing molars do not
      have to be replaced in order to prevent TMD pain.

PMID- 24452827
TI  - Mineral trioxide aggregate versus formocresol pulpotomy: a systematic review and
      meta-analysis of randomized clinical trials.
AB  - OBJECTIVES: This study systematically reviewed randomized clinical trials (RCTs)
      investigating the effectiveness of primary molar pulpotomies with mineral
      trioxide aggregate (MTA) and formocresol. The study also aimed to assess the
      possible association of reported prognostic factors on the success rate and
      relative risk using meta-regression analysis. MATERIALS AND METHODS: A
      comprehensive literature search using Medline, EMBASE, and Cochrane Central
      databases up to March 2013 was conducted. After scoring and data extraction of
      qualified trials (n = 19, representing 1,585 patients), meta-analyses were
      performed using Mantel-Haenszel model and inverse variance-weighted method.
      RESULTS: The results revealed that MTA is more effective than formocresol in
      primary molars pulpotomy, resulting in a lower failure rate with a relative risk
      of 0.26 (CI, 0.13-0.49), 0.37 (CI, 0.19-0.70), and 0.41 (CI, 0.25-0.68) for 6-,
      12-, and 24-month follow-ups (test for statistical heterogeneity: p = 0.99, p =
      0.98, and p = 0.23), respectively. Compared to amalgam restoration, success rate
      was significantly greater with SS crown (P < 0.05); however, no evidence for
      association between other reported prognostic factors such as selection of
      first/second molar, upper/lower jaw, gender, and various follow-up times with
      treatment success was observed. CONCLUSIONS: Based on the quality, homogeneity,
      and sufficient number of included RCTs, primary molar pulpotomy with MTA can
      produce a higher success rate in comparison with formocresol. CLINICAL RELEVANCE:
      When compared with formocresol, MTA pulpotomy is superior in treating primary
      molars.

PMID- 24452828
TI  - Quality of care for patients with acute coronary syndromes as a function of
      hospital revascularization capability: Insights from get with the guidelines-CAD.
AB  - BACKGROUND: Revascularization availability at US hospitals varies and may impact
      care quality for acute coronary syndrome patients. HYPOTHESIS: The hypothesis of
      this study was that there would be differences in care quality at Get With The
      Guidelines-Coronary Artery Disease (GWTG-CAD) hospitals based on
      revascularization capability. METHODS: For acute coronary syndrome patients
      admitted to GWTG-CAD hospitals between 2000 and 2010, care quality at hospitals
      with or without revascularization capability was examined by assessing conformity
      with performance and quality measures. RESULTS: This study included 95 999 acute
      coronary syndrome patients admitted to 310 GWTG-CAD hospitals. There were 89 000
      patients admitted to 226 revascularization-capable hospitals and 6999 patients
      admitted to 84 hospitals without revascularization capability included. Adjusted
      multivariate analysis demonstrated that 8 of the 19 measures were more frequently
      performed in the revascularization cohort: aspirin (odds ratio [OR]: 1.41, 95%
      confidence interval [CI]: 1.04-1.92), clopidogrel (OR: 2.31, 95% CI: 1.78-3.00),
      lipid-lowering therapies at discharge (OR: 1.39, 95% CI: 1.04-1.87), lipid
      lowering therapies for low-density lipoprotein >100 mg/dL (OR: 1.85, 95% CI: 1.23
      2.77), achievement of blood pressure <140/90 mm Hg (OR: 1.20, 95% CI: 1.03-1.40),
      LDL recorded (OR: 1.47, 95% CI: 1.05-2.06), and recommendations offered for
      physical activity (OR: 3.82, 95% CI: 2.23-6.55) or weight management (OR: 1.74,
      95% CI: 1.12-2.69). CONCLUSIONS: The GWTG-CAD revascularization hospitals were
      associated with better performance in some, but not all, measures assessed.
      Although the difference in conformity between hospital types was modest for
      performance measures but more variable for quality measures, room for improvement
      exists in key aspects of care.

PMID- 24452829
TI  - High-performance blue phosphorescent OLEDs using energy transfer from exciplex.
AB  - An efficient energy transfer from an exciplex between a sulfone and an arylamine
      derivatives to a blue phosphorescent emitter enables OLED performances among the
      best, of over 50 lm W(-1) at 100 cd m(-2) . The formation of the exciplex
      realizes a barrier-free hole-electron recombination pathway, thereby leading to
      high OLED performances with an extremely low driving voltage of 2.9 V at 100 cd
      m(-2) . 

PMID- 24452830
TI  - A hindbrain segmental scaffold specifying neuronal location in the adult
      goldfish, Carassius auratus.
AB  - The vertebrate hindbrain develops as a series of well-defined neuroepithelial
      segments or rhombomeres. While rhombomeres are visible in all vertebrate embryos,
      generally there is not any visible segmental anatomy in the brains of adults.
      Teleost fish are exceptional in retaining a rhombomeric pattern of reticulospinal
      neurons through embryonic, larval, and adult periods. We use this feature to map
      more precisely the segmental imprint in the reticular and motor basal hindbrain
      of adult goldfish. Analysis of serial sections cut in three planes and computer
      reconstructions of retrogradely labeled reticulospinal neurons yielded a
      segmental framework compatible with previous reports and more amenable to
      correlation with surrounding neuronal features. Cranial nerve motoneurons and
      octavolateral efferent neurons were aligned to the reticulospinal scaffold by
      mapping neurons immunopositive for choline acetyltransferase or retrogradely
      labeled from cranial nerve roots. The mapping corresponded well with the known
      ontogeny of these neurons and helps confirm the segmental territories defined by
      reticulospinal anatomy. Because both the reticulospinal and the motoneuronal
      segmental patterns persist in the hindbrain of adult goldfish, we hypothesize
      that a permanent "hindbrain framework" may be a general property that is retained
      in adult vertebrates. The establishment of a relationship between individual
      segments and neuronal phenotypes provides a convenient method for future studies
      that combine form, physiology, and function in adult vertebrates.

PMID- 24452831
TI  - Micropatterned array to assess the interaction of single platelets with platelet
      factor 4-heparin-IgG complexes.
AB  - We report a strategy to generate by electron beam lithography high fidelity
      micropatterned arrays to assess the interaction of single platelets with
      immobilised ligands. As a proof-of-principle we functionalised the microarrays
      with platelet factor 4 (PF4)-heparin-IgG complexes. We embedded biotinylated
      water-soluble quantum dots into polyethylene glycol (PEG)-coated micropatterned
      arrays and functionalised them via streptavidin to bind biotinylated ligands,
      here biotinylated-PF4/heparin complexes. The integrity of the PF4/heparin
      complexes was shown by binding of anti-PF4/heparin antibodies. Ligand density was
      quantified by immunofluorescence and immunogold antibody labelling. Real-time
      calcium imaging was employed for read-out of single platelets activated on
      micropatterned surfaces functionalised with PF4/heparin-IgG complexes. With the
      smallest micropatterns (0.5x0.5 um) we show that single platelets become strongly
      activated by binding to surface-immobilised PF4/heparin-IgG, while on larger
      micropatterns (10x10 um), platelet aggregates formed. These findings that HIT
      antibodies can cause platelet activation on microarrays illustrate how this novel
      method opens new avenues to study platelet function at single cell level.
      Generating functionalized microarray surfaces to which highly complex ligands can
      be bound and quantified has the potential for platelet and other cell function
      assays integrated into high-throughput microfluidic microdevices. 

PMID- 24452832
TI  - Percutaneous transvesical chorionic villus sampling: a safe alternative method
      for difficult procedures?

PMID- 24452834
TI  - Validation of the English version of the Walking Estimated-Limitation Calculated
      by History (WELCH) questionnaire in patients with intermittent claudication.
AB  - The Walking Estimated-Limitation Calculated by History (WELCH) questionnaire has
      recently been proposed as a valid and simple instrument for assessing walking
      limitation in patients with intermittent claudication. The aim of this study was
      to validate an English version of the WELCH questionnaire in an English native
      population. Thirty-nine patients (ankle-brachial index 0.59 +/- 0.16, age 65 +/-
      11 years, 82% male) completed an English version of the WELCH questionnaire.
      Maximum walking distance was measured objectively using the Gardner-Skinner
      treadmill test and the 6-minute walk test. The median WELCH score was 24 (9-39).
      Maximum walking distances were 412 m (149-675 m) for the treadmill test and 381
      +/- 88 m for the 6-minute walking test. The Spearman's correlation coefficient
      was rho = 0.59 between the WELCH score and treadmill distance (p < 0.001) and rho
      = 0.82 between the WELCH score and 6-minute walk distance (p < 0.001). These
      findings suggest that the English version of the WELCH questionnaire is a valid
      instrument for assessing walking impairment in patients with intermittent
      claudication. 

PMID- 24452833
TI  - Syntaxin 31 functions in Glycine max resistance to the plant parasitic nematode
      Heterodera glycines.
AB  - A Glycine max syntaxin 31 homolog (Gm-SYP38) was identified as being expressed in
      nematode-induced feeding structures known as syncytia undergoing an incompatible
      interaction with the plant parasitic nematode Heterodera glycines. The observed
      Gm-SYP38 expression was consistent with prior gene expression analyses that
      identified the alpha soluble NSF attachment protein (Gm-alpha-SNAP) resistance
      gene because homologs of these genes physically interact and function together in
      other genetic systems. Syntaxin 31 is a protein that resides on the cis face of
      the Golgi apparatus and binds alpha-SNAP-like proteins, but has no known role in
      resistance. Experiments presented here show Gm-alpha-SNAP overexpression induces
      Gm-SYP38 transcription. Overexpression of Gm-SYP38 rescues G. max [Williams 82/PI
      518671], genetically rhg1 (-/-), by suppressing H. glycines parasitism. In
      contrast, Gm-SYP38 RNAi in the rhg1 (+/+) genotype G. max [Peking/PI 548402]
      increases susceptibility. Gm-alpha-SNAP and Gm-SYP38 overexpression induce the
      transcriptional activity of the cytoplasmic receptor-like kinase BOTRYTIS INDUCED
      KINASE 1 (Gm-BIK1-6) which is a family of defense proteins known to anchor to
      membranes through a 5' MGXXXS/T(R) N-myristoylation sequence. Gm-BIK1-6 had been
      identified previously by RNA-seq experiments as expressed in syncytia undergoing
      an incompatible reaction. Gm-BIK1-6 overexpression rescues the resistant
      phenotype. In contrast, Gm-BIK1-6 RNAi increases parasitism. The analysis
      demonstrates a role for syntaxin 31-like genes in resistance that until now was
      not known. 

PMID- 24452835
TI  - Risk of intracranial haemorrhage in patients with atrial fibrillation treated
      with novel oral anticoagulants: testing the equivalence margins between
      dabigratran, rivaroxaban and apixaban.

PMID- 24452836
TI  - Posttransplantation bone marrow assessment by quantifying hematopoietic cell
      derived mRNAs in plasma exosomes/microvesicles.
AB  - BACKGROUND: Bone marrow (BM) aspiration often can be a painful medical procedure.
      It is unavoidable, however, because hematopoietic precursor cells (HPC) exist
      only in BM and few escape to peripheral blood (PB). We hypothesized that HPCs
      might release exosomes and microvesicles (EMV) in BM, and the resulting EMV would
      penetrate into PB. Such BM-derived EMV might be identified in PB by measuring
      specific mRNAs produced by HPC. METHODS: Human plasma was applied to an EMV
      capture filter plate. After centrifugation, captured EMV were lysed on the filter
      plate. Resulting lysates were transferred to an oligo(dT)-immobilized microplate
      for mRNA isolation followed by reverse transcription PCR (RT-PCR). Using this
      system, myeloid-, erythroid-, and megakaryocyte-lineage-specific poly(A)(+) mRNAs
      were quantified in plasma obtained from 18 patients who had undergone
      hematopoietic stem cell transplantation (HSCT). RESULTS: When fluorescent
      liposomes were applied to the filter plate, more than 95% of applied liposomes
      were absorbed. When human plasma was applied, a scanning electron microscope
      showed EMV-like particles on the membrane of the filter plate. After RT-PCR,
      various HPC-specific mRNAs were detected, and the results were equivalent to
      those derived from the standard ultracentrifugation method. The levels of these
      mRNAs were undetectable after HSCT and became detectable 1-2 weeks after HSCT, a
      substantially earlier time point than with traditional hematological analysis.
      The recovery of EMV mRNA at day 15 corresponded to the final clinical outcome at
      day 180. CONCLUSIONS: HPC-derived mRNAs in plasma EMV may represent new
      biomarkers for the assessment of BM condition and could reduce the necessity for
      frequent BM aspiration.

PMID- 24452837
TI  - Life-course fertility patterns associated with childhood externalizing and
      internalizing behaviors.
AB  - Childhood behavioral problems have been associated with earlier childbearing, but
      their life-course reproductive consequences are unknown. The present study
      examined whether and how behavioral problems assessed in childhood predict
      fertility patterns over the life course in women and men. Participants were 9,472
      individuals from the British National Child Development Study (4,739 men and
      4,733 women). Childhood externalizing and internalizing behaviors were rated by
      teachers at ages 7 and 11. Information on fertility history was derived from
      interviews at ages 33, 42, and 46, including date of pregnancy, whether the
      pregnancy was planned or non-planned, and pregnancy outcome (live birth,
      miscarriages/stillbirth, induced abortion). Transition to parenthood and
      fertility rate were assessed using survival analysis and age-stratified
      regression models. In both sexes, higher externalizing behavior was associated
      with higher rate of pregnancies, especially non-planned pregnancies in
      adolescence and early adulthood, but this association attenuated or even reversed
      later in adulthood. Internalizing behavior was associated with lower pregnancy
      rates, especially planned pregnancies and later in adulthood, and particularly in
      men. In women, higher internalizing behavior was also associated with earlier
      transition to parenthood. Externalizing behavior in women predicted higher risk
      of miscarriages and induced abortions, while internalizing behavior predicted
      lower risk for these outcomes. These findings suggest that childhood behavioral
      problems have long-term associations with fertility behavior over the life
      course, including earlier transition to parenthood, lower probability of
      normative family formation later in adulthood, and higher risk of adverse
      pregnancy outcomes. 

PMID- 24452838
TI  - Regional alterations in cortical thickness and white matter integrity in
      amyotrophic lateral sclerosis.
AB  - Previous neuroimaging studies have revealed that both gray matter (GM) and white
      matter (WM) are altered in several morphological aspects in amyotrophic lateral
      sclerosis (ALS). However, the relations between GM and WM measures and their
      contributions to clinical features remain in doubt. In this study, we acquired
      high-resolution diffusion tensor imaging along with structural magnetic resonance
      imaging data on 20 patients with clinical evidence of ALS and 21 matched healthy
      controls. WM microstructural metrics and cortical thickness were measured to
      characterize the whole brain WM and GM degenerative patterns. Probabilistic
      diffusion tractography was used to reconstruct the tracts from the WM regions
      characterized by fractional anisotropy (FA) decrease in patients. Decreased FA
      and increased radial diffusivity was observed in WM regions of the bilateral
      corticospinal tracts (CST) and callosal motor fibers in the ALS patients, while
      the superior longitudinal fasciculus exhibited a changing trend. Cortical
      thinning was found in the anatomically congruent regions, including the motor
      related cortices (i.e., bilateral precentral gyri, dorsal premotor cortices, and
      left supplementary motor area), prefrontal and occipito-parietal regions.
      However, there was no significant relationship between FA reduction and cortical
      thinning. Finally, patients with faster clinical progression showed more severe
      cortical thinning of the left precentral gyrus and FA reduction of the left CST.
      Together, these findings suggest that ALS is multisystem degeneration involving
      both the widespread cortices and the underlying WM fibers. GM and WM changes
      might play distinct roles in the disease progression. 

PMID- 24452839
TI  - The protective role of interleukin-11 against neutron radiation injury in mouse
      intestines via MEK/ERK and PI3K/Akt dependent pathways.
AB  - BACKGROUND: Neutron irradiation (IR) has been proven to cause more serious damage
      than gamma IR. Preventing and curing neutron IR damage remains an urgent issue.
      AIMS: The objective of this study was to investigate the radioprotective effects
      of IL-11 against neutron IR-induced damage in small intestine of mice. METHODS:
      Mice were exposed to 3-Gy neutron IR whole body and then treated with 500 MUg/kg
      interleukin-11 (IL-11) intraperitoneally every day. Mice were observed at various
      time-points over 1-5 days after IR. IEC-6 cells were exposed to 4 Gy neutron IR,
      and 100 ng/mL rhIL-11 was added to culture medium. Cell proliferation activity
      was estimated by MTT assay and rates of apoptosis were estimated by flow
      cytometry. RESULTS: IL-11 slightly alleviated the incidence of diarrhea in the
      mice and promoted intestinal epithelia regeneration. In the in vitro study,
      neutron IR activated extracellular signal-regulated kinase (ERK)1/2
      phosphorylation in intestinal epithelial cells constitutively, which was
      initially suppressed and then activated later by IL-11. The MEK-specific
      inhibitor U0126 could antagonize the positive effect of IL-11 on cell growth.
      Phosphatidylinositol 3-kinase (PI3K)/Akt pathway activation was suppressed after
      neutron IR, but could be triggered by IL-11 to protect the cells. The PI3K
      inhibitor LY294002 suppressed the positive effect of IL-11 on cell growth, and
      antagonized the protective effect of IL-11 against cell death after neutron IR.
      CONCLUSION: IL-11 increases cell proliferation after neutron IR in MEK and PI3K
      dependent signaling pathways, but protects cells against death only in the PI3K
      dependent signaling pathway.

PMID- 24452840
TI  - Induction of murine TNBS colitis is strictly controlled by a modified method
      using continuous inhalation anesthesia with sevoflurane.
AB  - BACKGROUND: Trinitrobenzenesulfonic acid (TNBS)-induced colitis is one of the
      most widely used experimental colitis models. However, there is no standard
      procedure for inducing colitis by TNBS because it is difficult to achieve a
      uniform distribution of colitis. We have developed a modified method of murine
      TNBS-induced colitis that involves inhalation anesthesia with sevoflurane
      combined with both single and repeated TNBS administrations. AIMS: To compare the
      usefulness of our newly developed method for inducing murine TNBS-induced colitis
      with that of conventional intraperitoneal anesthesia. METHODS: TNBS in ethanol
      was administered to C57BL/6J mice held in an inverted vertical position either
      under continuous inhalation anesthesia with sevoflurane, in accordance with our
      newly developed method, or by intraperitoneal injection with 2.5 % avertin, in
      accordance with the conventional procedure. Body weight change, cytokine profile,
      and histological findings were examined during the course of colitis. RESULTS:
      The dispersion of anesthesia time, TNBS retention time, and nadir weight during
      the course of colitis was decreased using the newly developed method compared
      with the conventional procedure. Optimization of the modified TNBS-induced
      colitis, as evidenced by the predominant expression of Th1 and Th17 cytokines on
      day 7, was attained by the injection of 2.25 mg TNBS in 55 % ethanol. Regulation
      of the TNBS retention time using inhalation anesthesia with sevoflurane allowed
      strict control of the disease severity of TNBS-induced colitis. Using the
      modified method we were also able to develop a chronic TNBS-induced colitis model
      by repeated TNBS administration without excessive mortality of the mice.
      CONCLUSIONS: Our modified method for murine TNBS-induced colitis using continuous
      inhalation anesthesia with sevoflurane provides a better experimental colitis
      model following both single and repeated TNBS administrations.

PMID- 24452842
TI  - [Pigmented lesion at base of tongue: mucosal melanoma or amalgam tattoo?].

PMID- 24452841
TI  - Bone marrow cells enhance liver regeneration after massive hepatectomy in mice.
AB  - BACKGROUND: Recent evidence indicates that transplanted autologous bone marrow
      cells (BMCs) can be converted into functional liver cells. BMC therapy can
      improve hepatic function and increase the potential for liver regeneration in
      patients with serious liver damage. We investigated whether BMC therapy
      influenced liver regeneration after massive hepatectomy in mice. METHODS: Male
      C57/BL6 mice underwent 70 % hepatectomy, followed by injection of BMCs via the
      portal vein (PV group), BMCs via the tail vein (IV group), or saline via the
      portal vein (control group). Analysis of serum enzyme levels and liver histology
      was performed on postoperative days (POD) 1, 3, and 5. RESULTS: Compared with the
      control group, the rate of liver regeneration on POD 3 and 5 was significantly
      higher in the PV group, but not in the IV group. Examination of the mitotic index
      and Ki-67 labeling index revealed that the increased liver regeneration resulted
      from stimulation of DNA synthesis. On POD 3, the serum levels of interleukin (IL)
      6 and hepatocyte growth factor (HGF) were significantly higher and the expression
      of IL-6 and HGF mRNA in the remnant liver tended to be higher in the PV group
      than in the control group. Histological examination showed BMCs in the liver of
      the PV group, as well as conversion of BMCs into liver cells. CONCLUSIONS: Our
      findings indicate that the injection of BMCs via the portal vein, but not the
      injection of BMCs via the tail, enhances liver regeneration after massive
      hepatectomy in mice.

PMID- 24452843
TI  - [Drug-induced subacute cutaneous lupus erythematosus: repeated occurrence
      following treatment with terbinafine].
AB  - A woman developed subacute cutaneous lupus erythematosus (SCLE) in 1995 and 2013,
      each time 6 weeks after initiation of terbinafine therapy. Within the
      heterogeneous group of drug-induced SCLE terbinafine is considered the most
      common cause. The clinical, histopathological and laboratory findings of
      idiopathic and drug-induced SCLE are largely identical. The pathogenesis of drug
      induced SCLE is not known. Cytotoxic and immunological mechanisms are considered
      likely. The treatment of drug-induced SCLE is discontinuation of the suspected
      drug. In addition, corticosteroids are recommended alone or in combination with
      chloroquine or hydroxychloroquine. 

PMID- 24452845
TI  - Interactive video gaming compared with health education in older adults with mild
      cognitive impairment: a feasibility study.
AB  - OBJECTIVE: We evaluated the feasibility of a trial of Wii interactive video
      gaming, and its potential efficacy at improving cognitive functioning compared
      with health education, in a community sample of older adults with
      neuropsychologically defined mild cognitive impairment. METHODS: Twenty older
      adults were equally randomized to either group-based interactive video gaming or
      health education for 90 min each week for 24 weeks. Although the primary outcomes
      were related to study feasibility, we also explored the effect of the
      intervention on neuropsychological performance and other secondary outcomes.
      RESULTS: All 20 participants completed the intervention, and 18 attended at least
      80% of the sessions. The majority (80%) of participants were "very much"
      satisfied with the intervention. Bowling was enjoyed by the most participants and
      was also rated the highest among the games for mental, social, and physical
      stimulation. We observed medium effect sizes for cognitive and physical
      functioning in favor of the interactive video gaming condition, but these effects
      were not statistically significant in this small sample. CONCLUSION: Interactive
      video gaming is feasible for older adults with mild cognitive impairment, and
      medium effect sizes in favor of the Wii group warrant a larger efficacy trial.

PMID- 24452844
TI  - Immunobiology of critical pediatric asthma.
AB  - Asthma is a heterogeneous disease with numerous clinical phenotypes. Severe
      asthma constitutes about 10 % of all cases of asthma. There is significant
      geographic and regional variation in the incidence and severity of asthma. Other
      important factors include gender, ethnicity, living environment, lifestyle,
      socioeconomic class, and pathophysiology. These factors can often be identified
      as either genetic or environmental influences on asthma severity. The immune
      system derangements in severe asthma are poorly understood. Many molecules and
      cell types have been implicated in severe asthma, including neutrophils, airway
      epithelial cells, thymic stromal lymphopoietin, and even filaggrin. Recently,
      vitamin D has been thought to have a role in the severity of asthma. Aspirin
      exacerbated respiratory disease is an example of a phenotype that includes severe
      asthma as a feature. This suggests a role of leukotrienes or prostaglandins in
      the pathogenesis of severe asthma. Both the innate and adaptive immune system may
      play a role in the development of severe asthma. Besides filaggrin, other factors
      of the innate immune system, including TLR4 and TLR9 have been implicated in
      asthma. Airway epithelial cells possess pattern recognition receptors that
      recognize danger or pathogen-associated molecular patterns, and the result of
      binding of the ligand is the triggering of a signaling pathway that ultimately
      can lead to an activation of inflammatory mediators through the action of
      calcineurin and NF-kappaB. Components of the adaptive immune system, including
      TH2 and Th17 cells, have been implicated in the pathogenesis of asthma. The fact
      that so many molecules and cells may be variably involved in asthma patients,
      coupled with the presence of redundant pathways that lead to secretion of
      inflammatory mediators, make the development of effective drugs for the treatment
      of asthma extremely difficult. A better understanding of the heterogeneity and
      what drives this diversity on a genetic and epigenetic level will help to develop
      strategies for novel therapeutic agents or methods. 

PMID- 24452846
TI  - Role of metallothioneins as danger signals in the pathogenesis of colitis.
AB  - Inflammatory bowel diseases (IBDs) are recurrent intestinal pathologies
      characterized by a compromised epithelial barrier and an exaggerated immune
      activation. Mediators of immune cell infiltration may represent new therapeutic
      opportunities. Metallothioneins (MTs) are stress-responsive proteins with immune
      modulating functions. Metallothioneins have been linked to IBDs, but their role
      in intestinal inflammation is inconclusive. We investigated MT expression in
      colonic biopsies from IBDs and acute infectious colitis patients and healthy
      controls and evaluated MT's role in experimental colitis using MT knockout mice
      and anti-MT antibodies. Antibody potential to target extracellular MT and its
      mechanism was tested in vitro. Biopsies of patients with active colitis showed
      infiltration of MT-positive cells in a pattern that correlated with the grade of
      inflammation. MT knockout mice displayed less severe acute dextran sulphate
      sodium (DSS)-induced colitis compared to congenic wild-type mice based on
      survival, weight loss, colon length, histological inflammation and leukocyte
      infiltration. Chronic DSS-colitis confirmed that Mt1 and Mt2 gene disruption
      enhances clinical outcome. Blockade of extracellular MT with antibodies reduced
      F4/80-positive macrophage infiltration in DSS- and trinitrobenzene sulphonic acid
      colitis, with a tendency towards a better outcome. Whole-body single-photon
      emission computer tomography of mice injected with radioactive anti-MT antibodies
      showed antibody accumulation in the colon during colitis and clearance during
      recovery. Necrotic and not apoptotic cell death resulted in western blot MT
      detection in HT29 cell supernatant. In a Boyden chamber migration assay,
      leukocyte attraction towards the necrotic cell supernatant could be abolished
      with anti-MT antibody, indicating the chemotactic potential of endogenous
      released MT. Our results show that human colitis is associated with infiltration
      of MT-positive inflammatory cells. Since antibody blockade of extracellular MT
      can reduce colitis in mice, MT may act as a danger signal and may represent a
      novel target for reducing leukocyte infiltration and inflammation in IBD
      patients.

PMID- 24452847
TI  - Synergism between upregulation of Rab7 and inhibition of autophagic degradation
      caused by mycoplasma facilitates intracellular mycoplasma infection.
AB  - Following fusion of a mycoplasma with a host cell membrane, the inserted
      components of mycoplasma may then be transported through the endocytic pathway.
      However, the effects of mycoplasmas on the host cell endomembrane system are
      largely unknown. In this study, mycoplasma-induced changes in the dynamics of
      endocytic and autophagic systems were investigated. Endocytosis and autophagy are
      two major processes involved in the survival of intracellular prokaryotic
      pathogens. It was found that, immediately following infection, mycoplasmas induce
      endocytosis in the host cell; however, in the long term the mycoplasmas suppress
      turnover of the components of the endocytic pathway. Immunofluorescence
      microscopy revealed that Rab7 and LC3-II are recruited to the intracellular
      mycoplasma-containing compartments. Western blot analysis and quantitative
      reverse transcription-polymerase chain reaction (qPCR) showed that mycoplasmas
      increase expression of Rab7 by upregulating transcription, but increase levels of
      LC3-II and p62 by post-translational regulation. Furthermore, it was demonstrated
      that mycoplasma infection causes inhibition of autophagic degradation of LC3-II
      and p62. In addition, it was found that upregulation of Rab7 and inhibition of
      autophagic degradation synergistically contributes to intracellular mycoplasma
      accumulation. In conclusion, these findings suggest that mycoplasmas may
      manipulate host cell endosomal and autophagic systems in order to facilitate
      intracellular infection.

PMID- 24452848
TI  - Specific substrate recognition and thioester intermediate determinations in
      ubiquitin and SUMO conjugation cascades revealed by a high-sensitive FRET assay.
AB  - Ubiquitin and ubiquitin-like proteins (Ubls), such as SUMO, are covalently
      conjugated to their targets by related, but distinct enzymatic conjugation
      reactions that involve the dynamic E1-E2-E3 enzyme cascade. E1s activate Ubls by
      catalyzing Ubl C-terminal adenylation, with the help of ATP, to form a covalent
      thioester bond. Subsequently, Ubls are transferred to E2 to generate a thioester
      linked product. In previous studies, we showed the dynamic processes and
      thioester intermediates of SUMO with its E1 and E2 conjugating enzymes. Studies
      of the enzyme specificity of the Ubl conjugation cascade are normally carried out
      by tedious biochemical processes, and the reaction intermediates are often
      difficult to capture because they are unstable and have short half-lives. Here,
      using our recently developed robust quantitative FRET-based technology, we
      describe systematic investigations of enzymatic specificity and thioester
      intermediate determination of ubiquitin with its E1-E2 ligases in conjugation
      with SUMO and its ligases. Our technology easily determined the strong
      specificity of enzyme-substrate interactions and thioester intermediates in
      ubiquitination and SUMOylation cascades. The traditional FRET pair ECFP/EYFP
      lacked adequate signals for these assays. However, in contrast, the highly
      sensitive FRET pair CyPet/YPet was easily harnessed to define the reaction
      specificities and intermediates. In addition, the thioester intermediates can be
      readily monitored by a newly defined FRET index parameter. These results provide
      an example of a systems biology approach to determine Ubl conjugation specificity
      and demonstrate that a robust FRET technology can be used to identify enzymes and
      substrates in other Ubl pathways. 

PMID- 24452849
TI  - Short-term efficacy and safety of sitagliptin treatment in long-term stable renal
      recipients with new-onset diabetes after transplantation.
AB  - BACKGROUND: New-onset diabetes after transplantation (NODAT) is a common
      complication after renal transplantation. There are limited available oral drugs
      to treat hyperglycaemia in this population owing to reduced renal function,
      potential interactions with immunosuppressive drugs and adverse effects such as
      hypoglycaemic events that may increase the cardiovascular risk. This study was
      initiated to investigate efficacy and safety of sitagliptin treatment that may
      represent a novel alternative in renal transplant recipients. METHODS: Nineteen
      long-term stable renal transplant recipients with NODAT were included in a
      controlled, cross-over study and randomized to first receive either sitagliptin
      50-100 mg/day or a sitagliptin-free period of 4 weeks. Median age (interquartile
      range, IQR) was 67 (62-72) years (12 males/7 females), all studied 1 (1-3) year
      after transplantation. The immunosuppressive regimen was a triple calcineurin
      inhibitor-based therapy. Oral glucose tolerance test (OGTT) with insulin and C
      peptide responses and laser Doppler (LD) flowmetry assessment of endothelial
      function were performed at baseline and after each treatment period. Home
      measurements of plasma glucose were performed daily during the study. RESULTS:
      The median (IQR) first- and second-phase insulin secretion responses increased
      significantly by 56.3% (45.2-112.6%, P = 0.005) and 39.3% (26.5-81.0%, P =
      0.006), respectively, following sitagliptin treatment as compared with no
      sitagliptin treatment. Fasting and 2-h plasma glucose concentrations fell
      significantly {0.9 mmol/L [0.5-1.7 mmol/L (16.2 mg/dL), P = 0.003] and 2.9 mmol/L
      [0.5-6.4 mmol/L (52.3 mg/dL), P = 0.004], respectively}, as did also home
      measurements of plasma glucose. Endothelial function and plasma markers of
      cardiovascular risk were unaffected. No serious adverse events were observed. Two
      mild and asymptomatic hypoglycaemic episodes were observed in combination with
      glipizide. CONCLUSIONS: Sitagliptin increases insulin secretion and reduces
      fasting and postprandial plasma glucose in renal transplant recipients with
      NODAT. The short-term treatment was well tolerated, and sitagliptin seems safe in
      this population.

PMID- 24452850
TI  - Endometrial vascularity is lower in pregnancies with pregnancy-induced
      hypertension or small-for-gestational-age fetus in live birth after in-vitro
      fertilization.
AB  - OBJECTIVE: To assess the relationship between endometrial/subendometrial
      vascularity and the risk of pregnancy-induced hypertension (PIH) or small-for
      gestational-age (SGA) fetuses in women who had a live birth following in-vitro
      fertilization (IVF). METHODS: This was a retrospective study of women who had a
      live birth after IVF from November 2002 to December 2004. Only women with a
      singleton pregnancy (n = 104) were included for analysis. Three-dimensional
      ultrasound measurement with power Doppler of the endometrial and subendometrial
      regions was performed on the day of oocyte retrieval in stimulated IVF cycles or
      on luteinizing hormone surge + 1 day in frozen-thawed embryo transfer cycles to
      measure the endometrial volume and the vascularization index (VI), flow index
      (FI) and vascularization flow index (VFI) of the endometrial and subendometrial
      regions. Pregnancy outcomes were also reviewed. RESULTS: Eight women (7.7%) had
      PIH or an SGA fetus. Women in the PIH/SGA group had significantly lower
      endometrial VI (0.504 vs 1.051; P = 0.023) and VFI (0.121 vs 0.253; P = 0.023)
      than those in the non-PIH/SGA group. However endometrial FI was significantly
      higher in the PIH/SGA group (23.04 vs 22.71; P = 0.028). There were no
      significant differences in subendometrial indices between the two groups.
      CONCLUSION: Women who had a live birth following IVF and whose pregnancy was
      complicated by PIH or an SGA fetus had significantly lower endometrial
      vascularity in terms of VI and VFI than did women without PIH or SGA.

PMID- 24452851
TI  - Determinants of trends in loneliness among Dutch older people over the period
      2005-2010.
AB  - OBJECTIVE: This study aims to investigate the influence of socio-demographic,
      health, and municipal characteristics on trends in loneliness among community
      dwelling elderly people. METHOD: Data were gathered from 4,868 and 4,773 non
      institutionalized elderly people aged 65 years and above in a health survey in
      2005 and 2010, respectively. Crude and adjusted multilevel models were analyzed
      to study the independent associations of study year and socio-demographic,
      health, and municipal characteristics with loneliness. RESULTS: Overall and
      across municipalities, loneliness estimates did not significantly differ between
      2005 and 2010. However, among the sub-group with activity limitations, loneliness
      was higher in 2010 compared with 2005. DISCUSSION: This study indicates a
      constant trend in loneliness in the total population and across sub-groups with
      the exception of participants with one or more activity limitations, where
      loneliness increased. Individual socio-demographic and health characteristics
      were explanatory factors for variation in loneliness over time, whereas municipal
      characteristics were not.

PMID- 24452852
TI  - Physically flexible, rapid-response gas sensor based on colloidal quantum dot
      solids.
AB  - A gas sensor based on PbS colloidal quantum dots (CQDs) is constructed on a paper
      substrate, yielding flexible, rapid-response NO2 gas sensors, fabricated from the
      solution phase. The devices are highly sensitive and fully recoverable at room
      temperature, which is attributed to the excellent access of gas molecules to the
      CQD surface, realized by surface ligand removal, combined with the desirable
      binding energy of NO2 with the PbS CQDs.

PMID- 24452855
TI  - Mesenchymal stem cell-based tissue engineering strategies for repair of articular
      cartilage.
AB  - Restoration of articular cartilage function and structure following pathological
      or traumatic damage is still considered a challenging problem in the orthopaedic
      field. Currently, tissue engineering-based reconstruction of articular cartilage
      is a feasible and continuously developing strategy to restore structure and
      function. Successful articular cartilage tissue engineering strategy relies
      largely on several essential components including cellular component, supporting
      3D carrier scaffolding matrix, bioactive agents, proper physical stimulants, and
      safe gene delivery. Designing the right formulations from these components remain
      the main concern of the orthopaedic community. Utilization of mesenchymal stem
      cells (MSCs) for articular cartilage tissue engineering is continuously
      increasing compared to use of chondrocytes. Various sources of MSCs have been
      investigated including adipose tissue, amniotic fluid, blood, bone marrow,
      dermis, embryonic stem cells, infrapatellar fat pad, muscle, periosteum,
      placenta, synovium, trabecular bone, and umbilical cord. MSCs derived from bone
      marrow and umbilical cord are currently in different phases of clinical trials. A
      wide range of matrices have been investigated to develop tissue engineering-based
      strategies including carbohydrate-based scaffolds (agarose, alginate,
      chitosan/chitin, and hyaluronate), protein-based scaffolds (collagen, fibrin, and
      gelatin), and artificial polymers (polyglycolic acid, polylactic acid,
      poly(lactic-co-glycolic acid), polyethylene glycol, and polycaprolactone).
      Collagen-based scaffolds and photopolymerizable PEG-based scaffolds are currently
      in different phases of clinical trials. TGF-beta1, TGF-beta3, BMP-2, and hypoxic
      environment are the recommended bioactive agents to induce optimum chondrogenesis
      of MSCs, while TGF-beta1, TGF-beta3, SOX-9, BMP-2, and BMP-7 genes are the best
      candidate for gene delivery to MSCs. Electromagnetic field and the combination of
      shear forces/dynamic compression are the best maturation-promoting physical
      stimulants.

PMID- 24452853
TI  - Synergies of phosphatidylserine and protein disulfide isomerase in tissue factor
      activation.
AB  - Tissue factor (TF), the cellular receptor and cofactor for factor VII/VIIa,
      initiates haemostasis and thrombosis. Initial tissue distribution studies
      suggested that TF was sequestered from the circulation and only present at
      perivascular sites. However, there is now clear evidence that TF also exists as a
      blood-borne form with critical contributions not only to arterial thrombosis
      following plaque rupture and to venous thrombosis following endothelial
      perturbation, but also to various other clotting abnormalities associated with
      trauma, infection, or cancer. Because thrombin generation, fibrin deposition, and
      platelet aggregation in the contexts of haemostasis, thrombosis, and pathogen
      defence frequently occur without TF de novo synthesis, considerable efforts are
      still directed to understanding the molecular events underlying the conversion of
      predominantly non-coagulant or cryptic TF on the surface of haematopoietic cells
      to a highly procoagulant molecule following cellular injury or stimulation. This
      article will review some of the still controversial mechanisms implicated in
      cellular TF activation or decryption with particular focus on the coordinated
      effects of outer leaflet phosphatidylserine exposure and thiol-disulfide exchange
      pathways involving protein disulfide isomerase (PDI). In this regard, our recent
      findings of ATP-triggered stimulation of the purinergic P2X7 receptor on myeloid
      and smooth muscle cells resulting in potent TF activation and shedding of
      procoagulant microparticles as well as of rapid monocyte TF decryption following
      antithymocyte globulin-dependent membrane complement fixation have delineated
      specific PDI-dependent pathways of cellular TF activation and thus illustrated
      additional and novel links in the coupling of inflammation and coagulation. 

PMID- 24452854
TI  - Impact of methodological variables on functional connectivity findings in autism
      spectrum disorders.
AB  - Growing evidence suggests that Autism Spectrum Disorder (ASD) involves
      abnormalities of multiple functional networks. Neuroimaging studies of ASD have
      therefore increasingly focused on connectivity. Many functional connectivity
      (fcMRI) studies have reported network underconnectivity in children and adults
      with ASD. However, there are notable inconsistencies, with some studies reporting
      overconnectivity. A previous literature survey suggested that a few
      methodological factors play a crucial role in differential fcMRI outcomes. Using
      three ASD data sets (two task-related, one resting state) from 54 ASD and 51
      typically developing (TD) participants (ages 9-18 years), we examined the impact
      of four methodological factors: type of pipeline (co-activation vs. intrinsic
      analysis, related to temporal filtering and removal of task-related effects),
      seed selection, field of view (whole brain vs. limited ROIs), and dataset.
      Significant effects were found for type of pipeline, field of view, and dataset.
      Notably, for each dataset results ranging from robust underconnectivity to robust
      overconnectivity were detected, depending on the type of pipeline, with intrinsic
      fcMRI analyses (low bandpass filter and task regressor) predominantly yielding
      overconnectivity in ASD, but co-activation analyses (no low bandpass filter or
      task removal) mostly generating underconnectivity findings. These results suggest
      that methodological variables have dramatic impact on group differences reported
      in fcMRI studies. Improved awareness of their implications appears indispensible
      in fcMRI studies when inferences about "underconnectivity" or "overconnectivity"
      in ASD are made. In the absence of a gold standard for functional connectivity,
      the combination of different methodological approaches promises a more
      comprehensive understanding of connectivity in ASD.

PMID- 24452856
TI  - Identification and refinement of two strong constitutive promoters for gene
      expression system of Schizosaccharomyces pombe.
AB  - Fission yeast Schizosaccharomyces pombe shares various important properties with
      higher eukaryotes and is now considered a useful host for elevated production of
      mammalian proteins for medicinal applications. The full-length nmt1 promoter has
      been widely used as a strong promoter in S. pombe expression system. In the
      present study, the promoters of the eno101 and gpd3 genes in S. pombe were
      identified as strong constitutive promoters. For convenient applications in the
      plasmids of S. pombe, these promoters were refined to 276-bp eno and 273-bp gpd
      promoters by deleting undesired sequences and examining the expression of
      reporter genes including lacZ and xynA. Both the refined eno and gpd promoters
      provided approximately 1.5-fold higher expression of LacZ than nmt1 promoter.
      Furthermore, gene expression under the control of the eno or gpd promoter was not
      repressed by the components of YES medium while nmt1 promoter was inhibited by
      thiamine in yeast extract. Therefore, both eno and gpd promoters offer
      opportunities for efficient production of recombinant proteins by S. pombe in
      high cell-density fermentation. 

PMID- 24452857
TI  - Cardiologists criticize US regulator for keeping intracranial stent on market.

PMID- 24452858
TI  - Mercury in the sediments of Vembanad Lake, western coast of India.
AB  - Mercury, a global pollutant, is popping up in places where it was never expected
      before and it burdens in sediments and other non-biological materials. It is
      estimated to have increased up to five times the pre-human level due to
      anthropogenic activities. Vembanad backwaters, one of the largest Ramsar site in
      India, which have extraordinary importance for its hydrological function, are now
      considered as one of the mercury hot spots in India. In this study, surface
      sediment samples of Vembanad Lake and nearshore areas have been seasonally
      analysed for total mercury and methyl mercury concentrations while the core
      sediment samples were analysed for total mercury. The results showed that the
      northern part of the lake was more contaminated with mercury than the southern
      part. The mercury concentration was relatively high in the subsurface sediment
      samples, indicating the possibility of historic industrial mercury deposition. A
      decreasing trend in the mercury level towards the surface in the core sediment
      was also observed. The geochemical parameters were also analysed to understand
      the sediment mercury chemistry. Anoxic conditions, pH and organic carbon, sulphur
      and Fe determined the presence of various species of mercury in the sediments of
      Vembanad Lake. The prevailing physical and geochemical conditions in Vembanad
      Lake have indicated the chances of chemical transformation of mercury and the
      potential hazard if the deposited mercury fractions are remobilised. 

PMID- 24452859
TI  - The need for ecological monitoring of freshwaters in a changing world: a case
      study of Lakes Annecy, Bourget, and Geneva.
AB  - Lakes Annecy, Bourget, and Geneva are large, deep carbonated peri-alpine lakes in
      eastern France. They are located in the same ecoregion but have been subject to
      differing degrees of anthropogenic pressure over the past decades. A comparative
      analysis of these ecosystems can therefore provide valuable information on how
      the lakes have responded to changes in phosphorus runoff, fish management
      practices, and global warming. Each of these lakes has undergone a restoration
      process, and changes in water quality and trophic state, as measured using
      parameters like transparency, chlorophyll a, nutrient concentrations, and
      phytoplankton biomass and structure, can be used to evaluate efforts made to
      preserve these ecosystems. Our results reveal that (1) peri-alpine lakes are
      exemplary cases of restoration in the world where freshwater eutrophication is on
      the increase, and (2) efforts must be maintained because of the new context of
      climate change, the effects of which on the quality and the ecological
      functioning of lakes are still poorly understood. 

PMID- 24452860
TI  - Using Landsat image time series to study a small water body in Northern Spain.
AB  - Ramsar Convention and EU Water Framework Directive are two international
      agreements focused on the conservation and achievement of good ecological and
      chemical status of wetlands. Wetlands are important ecosystems holding many plant
      and animal communities. Their environmental status can be characterised by the
      quality of their water bodies. Water quality can be assessed from biophysical
      parameters (such as Chlorophyll-a concentration ([Chla]), water surface
      temperature and transparency) in the deeper or lacustrine zone, or from
      bioindicators (as submerged aquatic vegetation) in the shallow or palustrine
      zone. This paper proves the use of Landsat time series to measure the evolution
      of water quality parameters and the environmental dynamics of a small water body
      (6.57 ha) in a Ramsar wetland (Arreo Lake in the North of Spain). Our results
      show that Landsat TM images can be used to describe periodic behaviours such as
      the water surface temperature or the phenologic state of the submerged vegetation
      (through normalized difference vegetation index, NDVI) and thus detect anomalous
      events. We also show how [Chla] and transparency can be measured in the
      lacustrine zone using Landsat TM images and an algorithm adjusted for mesotrophic
      Spanish lakes, and the resulting values vary in time in accordance with field
      measurements (although these were not synchronous with the images). The
      availability of this algorithm also highlights anomalies in the field data series
      that are found to be related with the concentration of suspended matter. All this
      potential of Landsat imagery to monitor small water bodies in wetlands can be
      used for hindcasting of past evolution of these wetlands (dating back to 1970s)
      and will be also useful in the future thanks to the Landsat continuity mission
      and the Operational Land Imager.

PMID- 24452861
TI  - Total synthesis of (+/-)-aspidophylline A.
AB  - A total synthesis of aspidophylline A, a pentacyclic akuammiline-type monoterpene
      indole alkaloid, is described. The synthesis features: 1) rapid access to a fully
      functionalized dihydrocarbazole through the desymmetrization of readily available
      2-allyl-2-(o-nitrophenyl)cyclohexane-1,3-dione; 2) an intramolecular
      azidoalkoxylation of an enecarbamate to install both the furoindoline ring and
      the azido functionality; and 3) an intramolecular Michael addition for the
      construction of the 2-azabicyclo[3.3.1]nonane ring system. 

PMID- 24452862
TI  - Distribution curve of waist-to-height ratio and its association with blood
      pressure among children and adolescents: study in a large population in an
      eastern coastal province, China.
AB  - Several studies have suggested that waist-to-height ratio (WHtR) is an accurate
      and easier index for evaluating abdominal obesity in both children and adults.
      The present study examined the distribution of WHtR and its association with
      blood pressure (BP) levels among children and adolescents in a large population
      in Shandong, China. A total of 38,810 students (19,453 boys and 19,357 girls)
      aged 7-17 years participated in this study. Height, waist circumference (WC), and
      BP of all subjects were measured, and WHtR was calculated. Abdominal obesity was
      defined as WHtR >=0.5; high BP status was defined as systolic blood pressure
      (SBP) and/or diastolic blood pressure (DBP) >=95th percentile for age and gender.
      Overall, 16.45% (95%CI: 15.93-16.97) and 7.80% (95%CI: 7.42-8.17) of boys and
      girls had a WHtR >=0.5. WHtR was positively correlated with SBP and DBP in both
      boys and girls. The mean values of SBP and DBP for both boys and girls were all
      significantly higher in the WHtR >=0.5 group than in the WHtR<0.5 group. Z-scores
      of BP and the prevalence of high BP increased with WHtR. The prevalence of high
      BP increased from 10.61 (boys) and 9.64% (girls) in the WHtR <0.34 group to 55.11
      (boys) and 51.97% (girls) in the WHtR >=0.58 group, an increase of 4.2- and 4.4
      times. We conclude that children and adolescents with high WHtR might have an
      increased risk of elevated BP. These findings highlight the importance of the
      prevention of abdominal obesity in order to prevent future-related problems such
      as hypertension in children and adolescents.

PMID- 24452863
TI  - Hepatic glucuronidation of isoneochamaejasmin a from the traditional Chinese
      medicine Stellera chamaejasme L. Root.
AB  - Isoneochamaejasmin A (INCA), a biflavonoid, is one of main active ingredients in
      the dried root of Stellera chamaejasme L., a widely used traditional Chinese
      medicine. In the present study, we identified the glucuronidation metabolite of
      INCA and characterized the UDP glucuronosyltransferases (UGTs) responsible for
      INCA glucuronidation. 7-O-glucuronide (M1) and 4'-O-glucuronide (M2) were
      identified by incubation of INCA with human liver microsomes (HLMs) in the
      presence of UDP glucuronic acid, and their structures were confirmed by high
      resolution mass spectrometry and nuclear magnetic resonance analyses. Although
      INCA is a single enantiomer molecule, its M1 metabolite showed two equal-size
      peaks on a piNAP stationary phase but only one peak on a C(18) stationary phase,
      indicating that the 7-/7''- and 4'-/4'''-hydroxyl groups of INCA were in
      different spatial configurations relative to each other. Among the recombinant
      human UGT isoform test and correlation analysis, UGT1A1, UGT1A3, and UGT1A9 were
      found to mediate M1 formation, whereas only UGT1A3 mediated M2 formation. Kinetic
      studies showed obvious species differences between human, mouse, rat, dog, and
      pig liver microsomes. UGT1A1, HLMs, and human intestinal microsomes, but not
      human kidney microsomes, exhibited substrate inhibition for the formation of M1.
      UGT1A1-mediated formation of M1 showed a 6- and 11-fold higher V(max) than did
      UGT1A3- and UGT1A9-mediated formation of M1, respectively. The results of the
      relative activity factor assay showed that UGT1A1 contributed approximately 75%
      in the formation of M1. These findings collectively indicate that UGT1A1 is the
      major enzyme in the formation of M1, whereas UGT1A3 is the major enzyme in the
      formation of M2.

PMID- 24452864
TI  - Hypericum perforatum modulates apoptosis and calcium mobilization through voltage
      gated and TRPM2 calcium channels in neutrophil of patients with Behcet's disease.
AB  - Behcet's disease (BD) is a chronic, inflammatory, and multisystemic condition
      although its pathogenesis is uncertain. Main component of St. John's wort
      (Hypericum perforatum, HP) is hyperforin and induces antiinflammatory and
      antioxidant properties. We aimed to investigate effects of HP on oxidative
      stress, apoptosis, and cytosolic-free Ca2+ [Ca2+](i) concentration in neutrophil
      of BD patients. Nine new-diagnosed active patients with BD and nine control
      subjects were included in the study. Disease activity was considered by clinical
      findings. Neutrophil samples were obtained from the patients and controls. The
      neutrophils from patients were divided into three subgroups and were incubated
      with HP, voltage-gated calcium channel (VGCC) blockers, (verapamil+dilitiazem)
      and non-specific TRPM2 channel blocker (2-aminoethyl diphenylborinate, 2-APB),
      respectively. The neutrophils were stimulated by fMLP as a Ca2+-concentration
      agonist and oxidative stress former. Caspase-3, caspase-9, apoptosis, lipid
      peroxidation, and [Ca2+](i) values were high in the patient groups, although cell
      viability, glutathione (GSH), and glutathione peroxidase (GSH-Px) values were low
      in patient group. However, the [Ca2+](i), caspase-3, and caspase-9 values
      decreased markedly in patient+HP group although GSH and GSH-Px values increased
      in the group. The [Ca2+](i) concentration was also decreased in the patient group
      by V+D, 2-APB, and HP incubations. In conclusion, we observed the importance of
      neutrophil Ca2+ entry, apoptosis, and oxidative stress through gating VGCC and
      TRPM2 channels in the neutrophils in the pathogenesis and activation of the
      patients with BD. HP induced protective effects on oxidative stress by modulating
      Ca2+ influx in BD patients.

PMID- 24452865
TI  - Transcription of click-linked DNA in human cells.
AB  - Click DNA ligation promises an alternative to the current enzymatic approaches
      for DNA assembly, with the ultimate goal of using efficient chemical reactions
      for the total chemical synthesis and assembly of genes and genomes. Such an
      approach would enable the incorporation of various chemically modified bases
      throughout long stretches of DNA, a feat not possible with current polymerase
      based methods. An unequivocal requirement for this approach is the
      biocompatibility of the resulting triazole-linked DNA. The correct function of
      this unnatural DNA linker in human cells is demonstrated here by using a click
      linked gene encoding the fluorescent protein mCherry. Reverse transcription of
      mRNA isolated from these cells and subsequent sequencing of the mCherry cDNA
      shows error-free transcription. Nucleotide excision repair (NER) is shown to not
      play a role in the observed biocompatibility by using a NER-deficient human cell
      line. This is the first example of a non-natural DNA linker being functional in a
      eukaryotic cell. 

PMID- 24452867
TI  - Proteomic analysis of the thermophilic methylotroph Bacillus methanolicus MGA3.
AB  - Bacillus methanolicus MGA3 is a facultative methylotroph of industrial relevance
      that is able to grow on methanol as its sole source of carbon and energy. The
      Gram-positive bacterium possesses a soluble NAD(+) -dependent methanol
      dehydrogenase and assimilates formaldehyde via the ribulose monophosphate (RuMP)
      cycle. We used label-free quantitative proteomics to generate reference proteome
      data for this bacterium and compared the proteome of B. methanolicus MGA3 on two
      different carbon sources (methanol and mannitol) as well as two different growth
      temperatures (50 degrees C and 37 degrees C). From a total of approximately 1200
      different detected proteins, approximately 1000 of these were used for
      quantification. While the levels of 213 proteins were significantly different at
      the two growth temperatures tested, the levels of 109 proteins changed
      significantly when cells were grown on different carbon sources. The carbon
      source strongly affected the synthesis of enzymes related to carbon metabolism,
      and in particular, both dissimilatory and assimilatory RuMP cycle enzyme levels
      were elevated during growth on methanol compared to mannitol. Our data also
      indicate that B. methanolicus has a functional tricarboxylic acid cycle, the
      proteins of which are differentially regulated on mannitol and methanol. Other
      proteins presumed to be involved in growth on methanol were constitutively
      expressed under the different growth conditions. All MS data have been deposited
      in the ProteomeXchange with the identifiers PXD000637 and PXD000638
      (http://proteomecentral.proteomexchange.org/dataset/PXD000637,
      http://proteomecentral.proteomexchange.org/dataset/PXD000638). 

PMID- 24452866
TI  - Structural characterization of IgG1 mAb aggregates and particles generated under
      various stress conditions.
AB  - IgG1 mAb solutions were prepared with and without sodium chloride and subjected
      to different environmental stresses. Formation of aggregates and particles of
      varying size was monitored by a combination of size-exclusion chromatography,
      Nanoparticle Tracking Analysis, Micro-flow Imaging (MFI), turbidity, and visual
      assessments. Stirring and heating induced the highest concentration of particles.
      In general, the presence of NaCl enhanced this effect. The morphology of the
      particles formed from mAb samples exposed to different stresses was analyzed from
      transmission electron microscopy and MFI images. Shaking samples without NaCl
      generated the most fibrillar particles, whereas stirring created largely
      spherical particles. The composition of the particles was evaluated for covalent
      cross-linking by SDS-PAGE, overall secondary structure by FTIR microscopy, and
      surface apolarity by extrinsic fluorescence spectroscopy. Freeze-thaw and shaking
      led to particles containing protein with native-like secondary structure. Heating
      and stirring produced IgG1-containing aggregates and particles with some non
      native disulfide cross-links, varying levels of intermolecular beta sheet
      content, and increased surface hydrophobicity. These results highlight the
      importance of evaluating protein particle morphology and composition, in addition
      to particle number and size distributions, to better understand the effect of
      solution conditions and environmental stresses on the formation of protein
      particles in mAb solutions.

PMID- 24452868
TI  - TSH stimulates the proliferation of vascular smooth muscle cells.
AB  - Subclinical hypothyroidism (SCH) was reported to be associated with
      atherosclerosis (AS) in recent studies. Thyroid hormone levels are normal in
      patients with SCH, but the levels of thyroid-stimulating hormone (TSH) are
      increased. Thyroid-stimulating hormone receptor (TSHR) in extra-thyroidal tissues
      plays a pathophysiological role in these conditions. Our previous results
      demonstrated that TSHR was functional in hepatocytes and revealed elevated total
      cholesterol levels in the serum, which were an independent risk factor for AS.
      TSHR is expressed in vascular smooth muscle cells (VSMCs), and VSMC proliferation
      plays an important role in the development of AS. Cell proliferation was measured
      by the MTT assay. Intracellular cyclic AMP (cAMP) was measured using a cAMP ELISA
      kit. Cells were analyzed using a flow cytometer to determine the cell-cycle phase
      of each cell. For the purpose of detecting cyclin A and cyclin D,
      immunohistochemical staining and western blots were performed. Real-time PCR was
      used to assess the VSMC phenotypes. TSH increased cell progression into the G2/M
      phases and induced VSMC proliferation; thus, functional TSHR was present on
      VSMCs. Furthermore, the expression of cyclin D1 and cyclin A was increased. In
      addition, the results indicated that VSMCs undergo a phenotypic transformation
      from a contractile state to a synthetic state after treatment with different
      concentrations of TSH. Elevated TSH can promote VSMC proliferation through the
      cAMP-dependent pathway.

PMID- 24452869
TI  - Familial Cushing syndrome due to thymic carcinoids in a multiple endocrine
      neoplasia type 1 kindred.
AB  - The objective of this study is to present a familial Cushing syndrome (CS) caused
      by multiple endocrine neoplasia type 1 (MEN-1)-associated thymic carcinoid.
      Immunohistochemistry, gene sequencing, loss of heterozygosity analysis, and
      Western blot were used to determine the expression of ACTH in MEN-1-related
      thymic tumors, MEN1 gene mutation, the pattern and extent of allelic deletion,
      and the expression of Menin in MEN-1-associated tumors, respectively. Tumor cells
      from thymus ectopic-secreted ACTH. A deletion involving the MEN1 gene locus was
      confirmed. The expression of Menin in MEN-1-associated tumors declined. To
      conclude, we presented an unusual kindred of MEN-1, which pointed out the
      significance of making screening of MEN-1 for both male and female patients with
      CS and thymic carcinoid. 

PMID- 24452870
TI  - Risk profiles for metabolic syndrome and its transition patterns for the elderly
      in Beijing, 1992-2009.
AB  - There have been few reports on the development of metabolic disorders, especially
      when they are considered as a cluster. The purpose of this study was to describe
      risk profiles for metabolic syndrome (MetS) in elderly dwellers in Beijing, and
      to find their transition patterns over time. Data were derived from Beijing
      longitudinal study of aging, a community-based cohort study hosted by Xuanwu
      hospital. There were 3,257 elderly people aged 55 years or over recruited in
      1992. MetS was assessed for the years 1992, 2000, and 2009. Finally, 363 subjects
      with complete information for components of MetS in the three years were included
      in the study. The criteria of MetS recommended by the joint interim statement
      criteria were adopted. Latent transition analysis was used to calculate the
      transition probabilities between adjacent visits. A risk typology consisting of
      four time-invariant groups was detected based on the components of MetS for all
      subjects. Low MetS risk group, BP risk group, BP-HDL risk group, and BP-FPG-TG
      risk group were found. The probability of staying at the same status was higher
      at the two intervals across 18 years. Four latent groups were extracted based on
      three assessments for the components of MetS, together with their transition
      patterns. Findings suggested various trajectories for MetS components. Different
      combinations of intervention strategy might be needed for MetS risk groups.

PMID- 24452871
TI  - Contribution of protein kinase Calpha in the stimulation of insulin by the down
      regulation of Cavbeta subunits.
AB  - Voltage-gated calcium (Cav) channels and protein kinase C (PKC) isozymes are
      involved in insulin secretion. In addition, Cavbeta, one of the auxiliary
      subunits of Cav channels, also regulates the secretion of insulin as knockout of
      Cavbeta3 (beta3(-/-)) subunits in mice led to efficient glucose homeostasis and
      increased insulin levels. We examined whether other types of Cavbeta subunits
      also have similar properties. In this regard, we used small interfering RNA
      (siRNA) of these subunits (20 MUg each) to down-regulate them and examined blood
      glucose, serum insulin and PKC translocation in isolated pancreatic beta cells of
      mice. While the down-regulation of Cavbeta2 and beta3 subunits increased serum
      insulin levels and caused efficient glucose homeostasis, the down-regulation of
      Cavbeta1 and beta4 subunits failed to affect both these parameters. Examination
      of PKC isozymes in the pancreatic beta-cells of Cavbeta2- or beta3 siRNA-injected
      mice showed that three PKC isozymes, viz., PKC alpha, betaII and theta,
      translocated to the membrane. This suggests that when present, Cavbeta2 and beta3
      subunits inhibited PKC activation. Among these three isozymes, only PKCalpha
      siRNA inhibited insulin and increased glucose concentrations. It is possible that
      the activation of PKCs betaII and theta is not sufficient for the release of
      insulin and PKCalpha is the mediator of insulin secretion under the control of
      Cavbeta subunits. Since Cavbeta subunits are present intracellularly, it is
      possible that they (1) inhibited the translocation of PKC isozymes to the
      membrane and (2) decreased the interaction between Cav channels and PKC isozymes
      and thus the secretion of insulin.

PMID- 24452872
TI  - Additional BRAF mutation analysis may have additional diagnostic value in thyroid
      nodules with "suspicious for malignant" cytology alone even when the nodules do
      not show suspicious US features.
AB  - The BRAF(V600E) mutation test has been more effective in thyroid nodules with
      suspicious US features than ones without suspicious features. Therefore, we
      investigated the role of the BRAF(V600E) mutation as an additional study to
      cytology in diagnosing a thyroid nodule without suspicious US features. This
      study was performed at Severance hospital from December 2010 through February
      2012. During this period, 2,650 patients with 2,918 nodules underwent FNA with an
      additional BRAF(V600E) mutation test. Among them, we excluded thyroid nodules
      with suspicious US features. Finally, 485 thyroid nodules in 466 patients (mean
      age 50.3 years; range 9-80 years) were included in this study. We compared the
      differences between patients with malignant and benign thyroid nodules. We
      evaluated the detection rates of the BRAF(V600E) mutation according to the
      Bethesda System for Reporting Thyroid Cytopathology (BSRTC). There were 60
      (60/485, 12.4 %) malignant and 425 (425/485, 87.6 %) benign nodules. The
      detection rate of the BRAF(V600E) mutation in thyroid nodules without suspicious
      US features was only 6.6 % (32/485). Most had malignant cytology (62.5 %, 20/32).
      For nodules without malignant cytology, only 12 nodules (2.6 %, 12/462) had the
      BRAF mutation. Among the 12 nodules, nine nodules were suspicious for malignancy
      on cytology. Additional BRAF mutation analysis shows additional diagnostic value
      in thyroid nodules with "suspicious for malignant" cytology alone even when the
      nodules do not show suspicious US features. Therefore, the test should be
      selectively performed in thyroid nodules without suspicious US features,
      considering cost-effectiveness as well as diagnostic accuracy.

PMID- 24452873
TI  - Ultrasonographic visceral fat thickness in the first trimester can predict
      metabolic syndrome and gestational diabetes mellitus.
AB  - The aim of this study is to evaluate whether ultrasonographic visceral fat
      thickness measurement in the early gestational period is useful for predicting
      the development of gestational diabetes mellitus (GDM) and metabolic syndrome
      (MS). The visceral fat thickness and subcutaneous fat thickness were measured via
      ultrasound at the first prenatal visit. The correlation between visceral and
      subcutaneous fat thickness and MS parameters, such as dyslipidemia, hypertension,
      and insulin resistance, was assessed. We also compared the use of visceral fat
      thickness measurement with body mass index (BMI) and waist circumference (WC)
      measurements for predicting the development of GDM. The subcutaneous fat
      thickness was found to be similar in the normal glucose metabolism and GDM groups
      at the first visit, whereas the visceral fat thickness was found to be
      considerably higher in the GDM groups (p = 0.04). The visceral fat thickness in
      the early stage of the gestation was correlated with hyperglycemia, dyslipidemia,
      high diastolic blood pressure, and insulin resistance. In contrast to
      subcutaneous fat thickness, BMI, and WC, only the visceral fat thickness was
      correlated with insulin resistance. The subcutaneous and visceral fat thicknesses
      at the first visit were significantly higher in the MS group (p = 0.02). There
      was a good correlation between visceral and subcutaneous fat thicknesses (r =
      0.492, p < 0.001); however, there were poor correlations between visceral fat
      thickness and BMI and WC (r = 0.338, p = 0.01; r = 0.312, p = 0.02). The visceral
      fat thickness seemed to be a more sensitive predictor of GDM than WC and BMI. The
      optimal cutoff points for predicting GDM were visceral fat thickness 19.5 mm
      [area under curve (AUC) = 0.66, p = 0.043], WC 103.5 cm (AUC = 0.64, p = 0.079),
      and BMI 34.5 (AUC = 0.64, p = 0.069). Ultrasonographic visceral fat thickness
      measurement in the early period of gestation may be an easy, safe, and cost
      effective scan test for predicting the development of metabolic diseases and GDM.

PMID- 24452875
TI  - Glucagon/insulin ratio in preoperative screening before pancreatic surgery:
      correlation with hemoglobin A1C in subjects with and without pancreatic cancer.
AB  - Role of impaired suppression of glucagon secretion in the pathogenesis of
      pancreatic cancer-associated diabetes has been suggested. We examined the
      correlation between glucagon/insulin ratio (G/I) after glucose challenge and
      hemoglobin A1C (A1C) in subjects with and without pancreatic cancer. Data were
      gathered from a preoperative screening 75-g oral glucose tolerance test in
      patients who would eventually undergo pancreatic resection. A multiple linear
      regression analysis was conducted using the following covariates: age, body mass
      index, hemoglobin, glucose and insulin levels at the corresponding time points,
      indices of insulin resistance, duration of diabetes, insulinogenic index, and use
      of glucose-lowering drugs. In subject group with pancreatic cancer (n = 45), but
      not in subject group without pancreatic cancer (n = 101), participants with A1C
      >= 6.5 % had significantly higher glucagon levels, lower insulin levels, and
      higher G/I ratios after the glucose challenge than those of the subjects with A1C
      <5.7 %. In the multiple linear regression analysis, there was an independent
      correlation between post-challenge G/I ratio and A1C in both groups. Some of the
      patients without pancreatic cancer had inappropriately elevated G/I ratios
      despite A1C <6.5 %. These patients were characterized by lower insulinogenic
      indices (p = 0.004) and less insulin resistance (p = 0.008). In conclusion, post
      challenge G/I ratio independently correlated with A1C in patients with pancreatic
      cancer. Although significant, the degree of correlation was weakened in the
      subjects without pancreatic cancer because some had lower insulin secretory
      reserve compensated by less insulin resistance, resulting in inappropriately
      elevated G/I ratios relative to A1C.

PMID- 24452874
TI  - Prevention of macrovascular disease in patients with short-duration type 2
      diabetes by multifactorial target control: an 8-year prospective study.
AB  - A longitudinal prospective study was undertook to investigate the effect of
      multifactorial target control, recommended by the American Diabetes Association
      (ADA), on macrovascular disease in patients with short-duration type 2 diabetes.
      Patients who were newly diagnosed with type 2 diabetes or within 1 year and had
      no previous vascular diseases or atherosclerosis plaques were enrolled in the
      present study. All patients received multifactorial intervention, with
      pharmacologic therapy targeting hyperglycemia, hypertension, dyslipidemia, along
      with secondary prevention of vascular disease with aspirin when necessary
      according to the ADA recommendation. Patients were followed up for 8 years (2002
      2010). The ultrasounds of arteries (carotid, iliac and femoral arteries) were
      measured every year. The primary endpoint was the time to the first occurrence of
      atherosclerosis plaques of the arteries. The second endpoint was clinical
      evidence of cardiovascular diseases. One hundred and forty-three patients were
      recruited, and the mean age was 50 (6.92) years. During the study,
      atherosclerosis plaques occurred in 49 patients. Systolic blood pressure less
      than 130 mmHg [hazard ratio (HR), 0.236; 95 % confidence interval (CI) 0.076
      0.734; P = 0.013] and fasting plasma glucose less than 7 mmol/l (HR, 0.457; 95 %
      CI 0.210-0.994; P = 0.048) were significantly associated with decreased onset of
      atherosclerosis plaques. Simultaneous target control of systolic blood pressure
      and fasting plasma glucose reduced the risk of atherosclerosis plaques by 18 % (P
      = 0.097) and cardiovascular diseases by 16 % (P = 0.046). Multifactorial target
      treatment in patients with short-duration type 2 diabetes can effectively reduce
      the risk of macrovascular complications.

PMID- 24452876
TI  - Non-functioning adrenal incidentalomas caused by 21-hydroxylase deficiency or
      carrier status?
AB  - Adrenal incidentalomas (AI) are an escalating clinical issue due to the
      increasing use of imaging techniques. Occasional patients with AIs have been
      reported who have subsequently been diagnosed with congenital adrenal hyperplasia
      (CAH) due to CYP21A2 mutations (21-hydroxylase deficiency) or carrier status. The
      objective of this investigation was to describe a larger cohort of patients with
      AI suspected to be caused by 21-hydroxylase deficiency or carrier status. All
      patients with AI and suspected CYP21A2 mutations during the last decade at a
      single center in Stockholm, Sweden, were included. Nine patients were identified
      (54 +/- 19-year-old at presentation). Two-thirds were females and two-thirds were
      from Sweden, while one-third was from the Middle East. Almost all (8/9) had
      children, but two had experienced fertility problems. Four of six women had
      symptoms of hyperandrogenism, and three had previously been diagnosed with
      polycystic ovary syndrome. The majority (7/9) had multiple AIs. In two cases, the
      initial suspicion had been adrenal cortical cancer, but increased urinary
      pregnanetriol had lead to the diagnosis of CAH. Basal serum 17
      hydroxyprogesterone was 10 (1.75-338) nmol/L. Seven was diagnosed with CAH (six
      non-classic, one simple virilizing). Two patients were considered to be carriers.
      However, in four patients, no CYP21A2 mutation was found and thus no confirmation
      of the diagnosis could be achieved. Patient presented with multiple AIs with
      hyperandrogenism or a Middle East origin screening for CAH or carrier status may
      be indicated.

PMID- 24452877
TI  - Screening for key genes associated with atopic dermatitis with DNA microarrays.
AB  - The aim of the present study was to identify key genes associated with atopic
      dermatitis (AD) using microarray data and bioinformatic analyses. The dataset
      GSE6012, downloaded from the Gene Expression Omnibus (GEO) database, contains
      gene expression data from 10 AD skin samples and 10 healthy skin samples.
      Following data preprocessing, differentially expressed genes (DEGs) were
      identified using the limma package of the R project. Interaction networks were
      constructed comprising DEGs that showed a degree of node of >3, >5 and >10, using
      the Osprey software. Functional enrichment and pathway enrichment analysis of the
      network comprising all DEGs and of the network comprising DEGs with a high degree
      of node, were performed with the DAVID and WebGestalt toolkits, respectively. A
      total of 337 DEGs were identified. The functional enrichment analysis revealed
      that the list of DEGs was significantly enriched for proteins related to
      epidermis development (P=2.95E-07), including loricrin (LOR), keratin 17 (KRT17),
      small proline-rich repeat proteins (SPRRs) and involucrin (IVL). The chemokine
      signaling pathway was the most significantly enriched pathway (P=0.0490978) in
      the network of all DEGs and in the network consisting of high degree-node DEGs
      (>10), which comprised the genes coding for chemokine receptor 7 (CCR7),
      chemokine ligand (CCL19), signal transducer and activator of transcription 1
      (STAT1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In
      conclusion, the list of AD-associated proteins identified in this study,
      including LOR, KRT17, SPRRs, IVL, CCR7, CCL19, PIK3R1 and STAT1 may prove useful
      for the development of methods to treat AD. From these proteins, PIK3R1 and KRT17
      are novel and promising targets for AD therapy.

PMID- 24452878
TI  - T-cell trafficking and anti-adhesion strategies in inflammatory bowel disease:
      current and future prospects.
AB  - The medical management of idiopathic inflammatory bowel disease (IBD) has
      historically been based upon the use of broad-spectrum anti-inflammatory drugs
      such as corticosteroids and thiopurines. Recently, the identification of novel
      mechanisms central to the pathophysiology of IBD has provided more specific
      targets, including inhibition of leukocyte trafficking to the gut. In this
      article, we discuss the molecular biology of intestinal leukocyte trafficking and
      review the emerging therapies that target this process, including vedolizumab,
      natalizumab, etrolizumab, PF-547659, alicaforsen, efalizumab, and emerging
      members of this class. 

PMID- 24452880
TI  - Associations between perceived social reactions to trauma-related experiences
      with PTSD and depression among veterans seeking PTSD treatment.
AB  - The Social Acknowledgment Questionnaire (SAQ; Maercker & Mueller, ) is a measure
      of trauma survivors' perceptions of social acknowledgment and disapproval from
      others, and these factors are shown to be associated with posttraumatic stress
      disorder (PTSD) among civilian trauma survivors. This study seeks to validate the
      structure of the SAQ among U.S. military veterans and test the hypothesis that
      family and general disapproval are associated with PTSD and depression among
      veterans. Participants were 198 U.S. veterans who experienced military trauma and
      completed an intake evaluation through a Veterans Affairs PTSD treatment program.
      Structural equation modeling (SEM) results supported a well-fitting 3-factor
      model for the SAQ that was similar to prior studies in capturing the constructs
      of social acknowledgment, general disapproval, and family disapproval. SEM
      results also showed that all 3 of the SAQ factors were associated with veterans'
      depression (-.31, .22, and .39, respectively), whereas only general disapproval
      was related to veterans' PTSD. This is the first study of which we are aware to
      investigate the factor structure of the SAQ in a veteran sample and to
      investigate the relationship between SAQ factors and trauma survivors'
      depression. Results build upon prior findings by showing the importance of
      positive and negative social reactions to veterans' traumatic experiences. 

PMID- 24452879
TI  - Oxycodone/Naloxone prolonged-release: a review of its use in the management of
      chronic pain while counteracting opioid-induced constipation.
AB  - A combination of prolonged-release (PR) oxycodone with PR naloxone (Targin((r)),
      Targiniq((r)), Targinact((r))) in one tablet with a fixed 2:1 ratio is available
      for the treatment of patients with severe pain, which can only be adequately
      managed with opioid analgesics. The aim of this formulation is to counteract
      opioid-induced constipation through the local antagonist effect of naloxone in
      the gut wall, while maintaining analgesia due to the low bioavailability of oral
      naloxone. Three large, 12-week, randomized, double-blind, phase III trials in
      patients with moderate to severe, chronic, non-malignant pain, plus a
      prospectively planned pooled analysis of two of these studies, demonstrated that
      oxycodone/naloxone PR improved bowel function, as measured by the bowel function
      index, compared with oxycodone PR. Additionally, oxycodone/naloxone PR relieved
      pain more effectively than placebo and no less effectively than oxycodone PR
      after 12 weeks. Phase II efficacy data in cancer patients are consistent with
      those observed in patients with non-malignant pain. Oxycodone/naloxone PR was
      generally well tolerated; the most frequently reported adverse events were of
      gastrointestinal origin, consistent with those known to occur with opioid
      therapy. Of note, numerically lower rates of constipation were observed in the
      oxycodone/naloxone PR group compared with the oxycodone PR group. A cost-utility
      analysis predicted that oxycodone/naloxone PR would be a cost-effective option
      compared with oxycodone PR in patients with non-malignant pain. Although more
      comparative data are needed, oxycodone/naloxone PR is an effective option for use
      in patients with severe chronic pain, particularly among those with opioid
      induced constipation. 

PMID- 24452881
TI  - New oral anticoagulant agents - general features and outcomes in subsets of
      patients.
AB  - During the past four years the phase III trials on stroke prophylaxis in atrial
      fibrillation and on treatment of venous thromboembolism have been completed for
      four new oral anticoagulants - dabigatran, apixaban, edoxaban and rivaroxaban.
      The studies have revealed advantages in terms of a reduced risk of bleeding, most
      importantly of intracranial bleeding. These anticoagulants also have favourable
      pharmacokinetics, eliminating the need for routine laboratory monitoring and dose
      adjustments. There are, however, some differences between the drugs in certain
      subsets of patients, according to patient characteristics or to indication for
      treatment. These features are reviewed here. The management of patients in
      association with invasive procedures or major bleeding is also discussed.
      Finally, a strategy of how to select patients for warfarin or the new
      anticoagulants and thereafter possibly also among the latter is outlined. 

PMID- 24452882
TI  - In vitro osteogenic cell proliferation, mineralization, and in vivo
      osseointegration of injection molded high-density polyethylene-based hybrid
      composites in rabbit animal model.
AB  - The present work reports the biocompatibility property of injection molded HDPE
      HA-Al2O3 hybrid composites. In vitro cytocompatibility results reveal that
      osteogenic cell viability and bone mineralization are favorably supported in a
      statistically significant manner on HDPE-20% HA-20% Al2O3 composite, in
      comparison to HDPE-40 wt.% HA or HDPE-40 wt.% Al2O3 The difference in
      cytocompatibility property is explained in terms of difference in substrate
      wettability/surface energy and importantly, both the cell proliferation at 7 days
      or bone mineralization at 21 days on HDPE-20% HA-20% Al2O3 composite are either
      comparable or better than sintered HA. The progressive healing of cylindrical
      femoral bone defects in rabbit animal model was assessed by implantation
      experiments over 1, 4 and 12 weeks. Based on the histological analysis as well as
      histomorphometrical evaluation, a better efficacy of HDPE-20% HA-20% Al2O3 over
      high-density polyethylene (HDPE) for bone regeneration and neobone formation at
      host bone-implant interface was established. Taken together, the present study
      unequivocally establishes that despite the presence of 20% Al2O3, HDPE-based
      hybrid composites are as biocompatible as HA in vitro or better than HDPE in
      vivo.

PMID- 24452883
TI  - The utility of transthoracic echocardiography to confirm central line placement:
      an observational study.
AB  - BACKGROUND: Ultrasound visualization of neck vessels is the standard method used
      to assist with internal jugular vein (IJV) central line placement. Nevertheless,
      this practice has not eliminated the risk of carotid puncture and/or inadvertent
      arterial cannulation. Transesophageal echocardiography (TEE) effectively verifies
      wire placement within the heart but is invasive and not always available. We
      examined the feasibility and potential utility of using transthoracic
      echocardiography (TTE) to verify the distal wire in the right atrium (RA) before
      dilation and cannulation of the IJV. METHODS: Following institutional Research
      Ethics Board approval and signed consent, 100 patients scheduled for elective
      cardiac surgery were recruited. As per standard practice at our institution, all
      patients were to have a central line inserted under general anesthesia with TEE
      visualization of the guidewire. Transesophageal echocardiography (apical or
      subcostal four-chamber images) was performed by one of four operators while
      another anesthesiologist performed central line placement. Following IJV
      puncture, blood was rapidly aspirated and reinjected to produce microbubbles.
      Subsequently, a 0.035-inch j-tipped flexible guidewire was inserted and
      visualized with TEE. The wire was then reinserted into the RA under TTE
      visualization. RESULTS: Overall, the RA was viewed 94% (95% confidence interval
      [CI] 87 to 98) of the time with TTE, and both the microbubbles and guidewire were
      detected 91% (95% CI 84 to 96) of the time. The subjects in whom the guidewire
      could not be well visualized had a higher mean body mass index (33.6 vs 28.8; P =
      0.01). CONCLUSIONS: Transthoracic echocardiography [corrected] is a feasible,
      noninvasive, and potentially useful method to confirm appropriate placement of
      the guidewire before dilation and cannulation of the IJV.

PMID- 24452884
TI  - Money: the elephant in the resident's room.

PMID- 24452885
TI  - Temporal bone fracture.
AB  - Transverse fractures account for approximately 20% of temporal bone fractures.
      They occur secondary to frontal or occipital head trauma, and they run
      perpendicular to the petrous pyramid.

PMID- 24452886
TI  - Unusual rhabdomyolysis of the masticator space.

PMID- 24452887
TI  - Cervical accessory tragus: an unusual pediatric neck mass.

PMID- 24452888
TI  - Polymorphous low-grade adenocarcinoma.

PMID- 24452889
TI  - How to approach a bilobed petrous apex granuloma: a case report.
AB  - Cholesterol granulomas are the most common lesions involving the petrous apex.
      However, they are still an uncommon finding overall, and they often remain
      undiagnosed until they have become extremely large and symptomatic. Many surgical
      approaches to the petrous apex exist. Factors that often influence the surgical
      approach include the surgeon's experience, the patient's anatomy, and the
      patient's hearing status. The purpose of this case report-which involved a 66
      year-old woman who was referred to our clinic for evaluation of severe headaches,
      dizziness, and left-sided pulsatile tinnitus-is to demonstrate the definitive
      need for an extended middle fossa approach when a bilobed petrous apex mass is
      encountered. 

PMID- 24452890
TI  - Concha bullosa mucocele and mucopyocele: a series of 4 cases.
AB  - Concha bullosa is an aerated turbinate in the nose. It is a common anatomic
      variant that can develop a mucocele if obstructed, which can further progress to
      become a mucopyocele if infected. A mucopyocele can expand and cause destruction
      of neighboring tissues. A review of the literature revealed only 10 cases
      previously reported. We describe 2 cases of mucocele and 2 cases of mucopyocele. 

PMID- 24452891
TI  - Vocal fold fixation caused by penetration of a high-velocity steel projectile.
AB  - Vocal fold fixation as a result of trauma caused by a foreign body is rare. We
      report a unique case of vocal fold fixation caused by traumatic penetration of a
      shard of steel in a 31-year-old steelworker. While the patient was at work, an
      airborne projectile suddenly pierced his neck and entered his larynx, causing
      progressive hoarseness and dyspnea. Flexible laryngoscopy detected no obvious
      foreign body, but it did reveal that the right vocal fold had become immobile.
      Computed tomography revealed that a 2.5-cm sliver of steel had become impacted in
      the right cricoarytenoid joint, which made the arytenoid cartilage unable to
      rotate. An emergency tracheostomy was performed with local anesthesia to
      construct a functioning airway, and then rigid laryngoscopy was performed with
      general anesthesia. The foreign body was removed with the assistance of a
      microscope and microscissors. Postoperatively, the patient immediately regained
      control of his right vocal fold, and he experienced no permanent injury. 

PMID- 24452892
TI  - A rare cause of submandibular swelling in a 12-year-old child: pleomorphic
      adenoma.
AB  - Pleomorphic adenoma is rare in pediatric populations, where viral and congenital
      problems are the usual culprits responsible for submandibular masses. We report
      the case of a 12-year-old child who presented with a painless right submandibular
      mass that had developed over the course of 4 months. The patient denied fever,
      erythema, and edema. The mass was diagnosed as a branchial cleft cyst before
      complete excision was performed. The pattern and etiology of a pleomorphic
      adenoma in children differs from those in adults. In children, it requires prompt
      and correct diagnosis to keep morbidity and mortality at a minimum. 

PMID- 24452893
TI  - When is a neck lump not a neck lump? Initial presentation of a solitary
      sternocleidomastoid muscle in an adult.
AB  - A 70-year-old woman was referred to us for evaluation of a presumed left-sided
      neck mass. The referral was based on the visual appearance of subtle neck
      asymmetry. The patient reported no ENT symptoms. Clinical examination and
      ultrasonography identified no pathology, but computed tomography revealed that
      the asymmetry was present because the patient's right sternocleidomastoid muscle
      (SCM) was absent. The SCM on the left side was normal. Congenital absence of an
      SCM is uncommon, and to the best of our knowledge, an initial presentation in an
      adult has not been previously reported in the literature. 

PMID- 24452895
TI  - Clinical management of a patient with advanced mucosal malignant melanoma in the
      sinonasal area.
AB  - We describe a case of mucosal malignant melanoma in the sinonasal area of a 65
      year-old woman. She presented with a history of nasal obstruction and epistaxis
      with subsequent tenderness, facial anesthesia involving cranial nerve V2, red
      eye, proptosis, diplopia, and conjunctival chemosis. Computed tomography detected
      a nonspecific solid mass that had involved the left maxillary sinus and
      surrounding tissues, with extension into the nasal cavity and invasion of the
      orbital floor and eye muscles. Histopathologic examination of the neoplasm
      revealed that it was a malignant melanoma. We performed a radical
      hemimaxillectomy that extended to the orbit, which allowed for radical excision
      of the tumor. Postoperatively, the patient received adjuvant chemotherapy and
      radiotherapy. Mucosal melanoma in the head and neck is a rare and highly
      malignant neoplasm. We suggest that malignant melanoma be suspected when a small
      round-cell tumor is found on light microscopy, and we confirm the usefulness of
      immunohistochemical investigations. 

PMID- 24452896
TI  - Primary amelanotic melanoma of the nasal cavity: a case report.
AB  - Primary mucosal malignant melanomas of the nose are rare, accounting for only 0.3
      to 2% of all cases of malignant melanoma and about 4% of all head and neck
      melanomas. The amelanotic variant of mucosal malignant melanoma is even more
      rare, and the prognosis is poor. This variant usually arises in locations in
      which it is not noticeable, and therefore it is usually diagnosed at an advanced
      clinical stage when symptoms eventually manifest. We report a case of locally
      advanced amelanotic melanoma of the nasal cavity in a 55-year-old woman who
      presented with complaints of nasal obstruction and intermittent bleeding on the
      right side of the nose for 3 months and a gradually progressive diffuse swelling
      over the right periorbital and maxillary areas for 2 months with associated pain
      for 15 days. She was diagnosed with amelanotic melanoma on the basis of clinical,
      radiologic, and pathologic findings. In view of her advanced disease, she
      declined surgery and was treated with chemoradiotherapy, and she experienced a
      significant alleviation of her symptoms. 

PMID- 24452897
TI  - A case of bilateral internal auditory canal osteomas.
AB  - Osteomas of the skull base are rare, benign, slowly progressing growths of dense
      cortical bone. Osteomas occurring in the internal auditory canal are extremely
      rare. These lesions have sometimes been linked with dizziness, sensorineural
      hearing loss, and/or tinnitus. Although there have been documented cases in which
      surgical excision has improved these symptoms, symptomatic relief is not always
      achieved with surgical management. Here we present, to the best of our knowledge,
      only the third reported case of bilateral osteomas of the internal auditory
      canal. An 82-year-old woman presented with an acute onset of vertigo without a
      history of trauma or ear infection. She reported two similar episodes occurring a
      few years earlier, with symptoms persisting for only a few days. Audiometry
      showed presbycusis. Computed tomography and magnetic resonance imaging identified
      bilateral internal auditory canal osteomas. The patient was treated
      conservatively, monitored, and had complete resolution of her symptoms. 

PMID- 24452898
TI  - Basaloid squamous cell carcinoma of the pinna: report of a rare case.
AB  - Basaloid squamous cell carcinoma (BSCC) is rare. We report a case of BSCC in a 60
      year-old woman who presented with a bleeding vascular growth on the left pinna.
      To the best of our knowledge, no case of BSCC of the pinna has been previously
      reported in the literature. We present this case to alert physicians that this
      highly aggressive variant of squamous cell carcinoma can appear on the pinna and
      therefore it should be considered in the differential diagnosis of lesions in
      this area. 

PMID- 24452899
TI  - Melioidosis of salivary glands with coexisting diabetes: management of a
      difficult case.
AB  - Melioidosis is an infectious disease caused by the gram-negative bacillus
      Burkholderia pseudomallei. Melioidosis is endemic in Southeast Asia and northern
      Australia. An important risk factor for the development of melioidosis is the
      presence of diabetes mellitus, which may increase the relative risk of infection
      by as much as 100-fold. We report a rare case of melioidosis of the parotid and
      submandibular gland with coexisting diabetes. This was successfully managed
      conservatively with intravenous ceftazidime followed by
      trimethoprim/sulfamethoxazole and doxycycline. 

PMID- 24452900
TI  - Bilateral dacryocystoceles as a rare cause of neonatal respiratory distress:
      report of 2 cases.
AB  - Although obstruction of the nasolacrimal duct is a fairly common finding in
      newborns, development of a dacryocystocele (nasolacrimal duct cyst) is uncommon.
      Bilateral dacryocystoceles that expand intranasally and cause respiratory
      distress in the newborn are rarer still. We present 2 cases of bilateral
      dacryocystoceles that caused neonatal respiratory compromise. Our first patient,
      a newborn girl, was managed successfully with probing of the nasolacrimal ducts
      and endoscopic marsupialization of the cysts. Our second patient, a newborn boy,
      responded well to conservative treatment with a nasal decongestant, lacrimal sac
      massage, and warm compresses. While bilateral dacryocystoceles are rare, they
      should be considered in cases of neonatal respiratory distress and concomitant
      nasal obstruction. 

PMID- 24452901
TI  - Recurrent chondro-osseous respiratory epithelial adenomatoid hamartoma of the
      nasal cavity in a child.
AB  - Chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH) is an
      extremely rare type of hamartoma. To the best of our knowledge, only 1 case has
      been previously reported. A 7-year-old girl presented with a case of COREAH of
      the bilateral nasal cavities. Polypous masses in both nasal cavities were
      resected endoscopically, and they were histologically diagnosed as COREAH. A
      large polypous mass recurred 1 year postsurgically on the right side only. A
      second endoscopic surgery was performed, and the lesion was confirmed to be
      recurrent COREAH. Hamartoma of the nasal cavity is rare and is generally
      considered to be self-limiting. This case suggests that nasal hamartomas may have
      neoplastic characteristics, and therefore require complete resection. 

PMID- 24452902
TI  - Recurrent pyogenic granuloma in a noncompliant patient.

PMID- 24452903
TI  - Endoscopic view of a biodegradable middle meatal spacer.

PMID- 24452904
TI  - Severe symptomatic hypocalcemia following total thyroidectomy in a patient with a
      history of Roux-en-Y gastric bypass surgery.
AB  - Patients who undergo a Roux-en-Y gastric bypass (RYGB) procedure are at moderate
      risk for calcium and vitamin D deficiency. Those who subsequently undergo thyroid
      or parathyroid surgery are at high risk for developing severe symptomatic
      hypocalcemia if they are not monitored and adequately treated prophylactically.
      We describe the case of a morbidly obese 40-year-old man who had undergone RYGB
      surgery 6 months prior to the discovery of metastatic papillary thyroid
      carcinoma. He subsequently underwent total thyroidectomy with central and
      bilateral neck dissection. Following surgery, he developed severe symptomatic
      hypocalcemia, as his calcium level fell to a nadir of 6.0 mg/dl. He required
      aggressive oral and intravenous repletion therapy with calcium, vitamin D, and
      magnesium for 10 days before hospital discharge. Providers should institute
      careful preoperative screening, patient counseling, and prophylactic calcium and
      vitamin D therapy for all thyroid surgery patients who have previously undergone
      RYGB surgery to prevent the development of severe and life-threatening
      hypocalcemia. Only a few reports of patients have been published on the dangers
      of thyroid and parathyroid surgery in patients who have undergone bariatric
      surgery. We report a new case to add to the body of literature on this patient
      population. We also review calcium homeostasis and supplementation as they relate
      to this situation. 

PMID- 24452905
TI  - Characterization of hindered amine light stabilizers employing capillary
      electrophoresis coupled to quadrupole time-of-flight mass spectrometry.
AB  - In the current work, a fast and reliable CE method for characterizing of six
      hindered amine light stabilizers (HALS), technical products commonly employed as
      UV-stabilizing agents for various polymeric materials, is presented. These
      compounds can be monomeric or oligomeric species whereby there is no or only
      limited information available concerning purity or actual structural composition
      of the respective stabilizer. Using a BGE based on formic acid with 10%
      acetonitrile, different constituents of several HALS could be separated by CE and
      identified employing QTOF/MS detection. In the case of Cyasorb 3529, ten
      different oligomers were discovered and possible structures were suggested based
      on exact mass measurements. The majority of the elucidated structures is not
      fully congruent with the information provided by the manufacturers. Furthermore,
      in the case of Chimassorb 119 and Tinuvin 770 impurities or unreacted compounds
      remaining from the manufacturing process could be identified. Besides performing
      such basic characterizations of technical grade HALS, the presented method is
      also shown to be suitable for a reliable identification of these stabilizers in
      real polymer samples. 

PMID- 24452906
TI  - The impact of vascular factors on language localization in the superior temporal
      sulcus.
AB  - The left superior temporal sulcus (STS) has been shown in numerous functional
      imaging studies to be a critical region for language processing, as it is
      reliably activated when language comprehension is compared with acoustically
      matched control conditions. Studies in non-human primates have demonstrated
      several subdivisions in the STS, yet the precise region(s) within the STS that
      are important for language remain unclear, in large part because the presence of
      draining veins in the sulcus makes it difficult to determine whether neural
      activity is localized to the dorsal or ventral bank of the sulcus. We used
      functional MRI to localize language regions, and then acquired several additional
      sequences in order to account for the impact of vascular factors. A breath
      holding task was used to induce hypercapnia in order to normalize voxel-wise
      differences in blood oxygen level-dependent (BOLD) responsivity, and veins were
      identified on susceptibility-weighted and T2*-weighted BOLD images, and masked
      out. We found that the precise locations of language areas in individual
      participants were strongly influenced by vascular factors, but that these
      vascular effects could be ameliorated by hypercapnic normalization and vein
      masking. After these corrections were applied, the majority of regions activated
      by language processing were localized to the dorsal bank of the STS.

PMID- 24452907
TI  - How "drug-like" are naturally occurring anti-cancer compounds?
AB  - We attempt to evaluate the "drug-likeness" of a collection of ~1500 natural
      products, exhibiting in vitro or in vivo activities against cancers of various
      forms, by using a set of calculated molecular descriptors. Compliance to
      Lipinski's "Rule of Five" and Jorgensen's "Rule of Three" have been used to
      assess oral availability, by making use of popular parameters like molecular
      weights, predicted lipophilicities, number of hydrogen bond donors/acceptors,
      predicted aqueous solubilities, number of primary metabolites and Caco-2
      permeabilities. Meanwhile 24 descriptors have been used to predict properties
      related to the absorption, distribution, metabolism, elimination, and toxicity
      (ADMET). The ADMET profiles of the anticancer natural products have been analyzed
      in comparision with the range of properties for 95 % of known drugs. Our results
      show that the computed parameters fall within the recommended range for about 42
      % of the studied compounds, while respectively 63 % and 69 % of the corresponding
      'drug-like' and 'lead-like' subsets had properties predicted to fall within the
      recommended range for 95 % of known drugs. The aim of giving a picture of how
      drug-like they are and bring out the need to return to natural sources in
      searching for anticancer lead compounds.

PMID- 24452908
TI  - DFT study of ozone dissociation on BC3 graphene with Stone-Wales defects.
AB  - Ozone (O3) adsorption on pristine Stone-Wales (SW) defective BC3 graphene-like
      sheets was investigated using density functional calculations. It was found that
      O3 is weakly adsorbed on the pristine sheet. Two types of SW-defective sheets
      were studied, SW-CC and SW-BC, in which a defect is formed by rotating a C-C or B
      N bond, respectively. O3 molecules were found to be more reactive on SW-BC
      defective sheets. It was predicted that O3 molecules are reduced to O2 molecules
      on SW-BC sheets, overcoming an energy barrier of 34.2 kcal/mol(-1) at the B3LYP
      level of theory and 27.2 kcal/mol(-1) at the BP98 level of theory. Therefore, SW
      BC sheets could potentially be employed as a metal-free catalyst for O3
      reduction. The HOMO-LUMO gap of a SW-BC sheet decreases from 2.16 to 1.21 eV
      after O3 dissociation on its surface in the most stable state.

PMID- 24452909
TI  - Burst speciation processes and genomic expansion in the neotropical annual
      killifish genus Austrolebias (Cyprinodontiformes, Rivulidae).
AB  - The extent to which genome sizes and other nucleotypic factors influence the
      phyletic diversification of lineages has long been discussed but remains largely
      unresolved. In the present work, we present evidence that the genomes of at least
      16 species of the neotropical rivulid killifish genus Austrolebias are unusually
      large, with an average DNA content of about 5.95 +/- 0.45 picograms per diploid
      cell (mean C-value of about 2.98 pg). They are thus larger than the genomes of
      very nearly all other diploid, i.e. non-(paleo) polyploid species of
      actinopterygian fishes so far reported. Austrolebias species appear to be
      conventional diploids in all other respects and there is no reason to believe
      that they arise from polyploid ancestors. The genome sizes reported for other
      rivulid killifishes, including a putative sister group, are considerably smaller
      and fall within the range typical of most other cyprinodontoid species.
      Therefore, it appears that the ancestor(s) of contemporary Austrolebias have
      undergone one or more episodes of genome expansion encompassing sudden speciation
      process during the Pleistocene. In addition, these findings are consistent with
      the hypothesis of a positive correlation between species richness and genome
      size.

PMID- 24452910
TI  - 3D nanostar dimers with a sub-10-nm gap for single-/few-molecule surface-enhanced
      raman scattering.
AB  - Plasmonic nanostar-dimers, decoupled from the substrate, have been fabricated by
      combining electron-beam lithography and reactive-ion etching techniques. The 3D
      architecture, the sharp tips of the nanostars and the sub-10 nm gap size promote
      the formation of giant electric-field in highly localized hot-spots. The
      single/few molecule detection capability of the 3D nanostar-dimers has been
      demonstrated by Surface-Enhanced Raman Scattering. 

PMID- 24452911
TI  - Mycobacterium tuberculosis RpfE crystal structure reveals a positively charged
      catalytic cleft.
AB  - Resuscitation promoting factor (Rpf) proteins, which hydrolyze the sugar chains
      in cell-wall peptidoglycan (PG), play key roles in prokaryotic cell elongation,
      division, and escape from dormancy to vegetative growth. Like other bacteria,
      Mycobacterium tuberculosis (Mtb) expresses multiple Rpfs, none of which is
      individually essential. This redundancy has left unclear the distinct functions
      of the different Rpfs. To explore the distinguishing characteristics of the five
      Mtb Rpfs, we determined the crystal structure of the RpfE catalytic domain. The
      protein adopts the characteristic Rpf fold, but the catalytic cleft is narrower
      compared to Mtb RpfB. Also in contrast to RpfB, in which the substrate-binding
      surfaces are negatively charged, the corresponding RpfE catalytic pocket and
      predicted peptide-binding sites are more positively charged at neutral pH. The
      complete reversal of the electrostatic potential of the substrate-binding site
      suggests that the different Rpfs function optimally at different pHs or most
      efficiently hydrolyze different micro-domains of PG. These studies provide
      insights into the molecular determinants of the evolution of functional
      specialization in Rpfs. 

PMID- 24452912
TI  - Epigallocatechin-3-gallate inhibits the proliferation and migration of human
      ovarian carcinoma cells by modulating p38 kinase and matrix metalloproteinase-2.
AB  - Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, has recently
      been reported to exhibit anticancer effects on a number of types of cancer cells
      in vitro; however, the molecular mechanisms of this anticancer effect remain
      poorly understood. In the current study, the effects of EGCG on the proliferation
      and migration of the OVCAR-3 human ovarian carcinoma cell line were investigated.
      Cells were treated with EGCG and their proliferation rates were determined by an
      MTT assay. In addition, cell migration was detected by transwell assay. The
      activity of mitogen-activated protein kinases (MAPKs) and the expression of
      matrix metalloproteinase-2/9 (MMP-2/9) were examined by western blotting. The
      results showed that EGCG significantly inhibited (P<0.05) the proliferation of
      OVCAR-3 cells in a time- and concentration-dependent manner. EGCG (100 uM) time
      dependently increased (P<0.05) the activity of p38, but not extracellular signal
      regulated kinases 1/2. SB203580, a specific p38 MAPK inhibitor, completely
      diminished EGCG-induced phosphorylation of p38 and partially blocked EGCG
      inhibited OVCAR-3 cell proliferation. Furthermore, EGCG (0-100 uM) dose
      dependently inhibited (P<0.05) OVCAR-3 cell migration. The protein expression
      levels of MPP-2, but not MMP-9, were dose-dependently decreased following
      treatment with EGCG (0-100 uM) for 48 h. These data indicated that EGCG inhibited
      OVCAR-3 cell proliferation and migration, potentially mediated via the activation
      of p38 MAPK and downregulation of the protein expression of MMP2. Thus, the
      therapeutic potential of EGCG for ovarian cancer requires further investigation.

PMID- 24452913
TI  - New Year's greetings from ESNR.

PMID- 24452915
TI  - Ultrastructure of spermatozoa in the seminal receptacle of the liver fluke
      Opisthorchis felineus (Rivolta, 1884).
AB  - The spermatozoon ultrastructure in the seminal receptacle of the liver fluke
      Opisthorchis felineus (Digenea, Opisthorchiidae), the agent of human
      opisthorchiasis endemic to Russia and Eastern Europe, was examined. The bean
      shaped seminal receptacle of O. felineus has a wall consisting of epithelial and
      muscle layers. Mature spermatozoa are located in the interior of the seminal
      receptacle, whereas vacuoles containing degenerating spermatozoa are detectable
      at the periphery. The mature spermatozoon of O. felineus has two axonemes of a 9
      + "1" pattern, a nucleus, two mitochondria, a lamellar body, two bundles of
      parallel cortical microtubules and an external ornamentation of the plasma
      membrane in the anterior area of the sperm. The lamellar body is likely to be the
      third mitochondrion of a small size. The cytoplasm of the spermatozoon is filled
      with numerous electron-dense granules of storage polysaccharides. Additionally,
      the ultrastructural characteristics of the seminal receptacle and spermatozoa of
      O. felineus were compared to available published data on other trematode species.
      The functional roles of the observed structures of this spermatozoon are
      discussed.

PMID- 24452916
TI  - Simultaneous priming with DNA encoding Sm-p80 and boosting with Sm-p80 protein
      confers protection against challenge infection with Schistosoma mansoni in mice.
AB  - Prophylactic efficacy of Sm-p80 was tested in the mouse model using DNA priming
      and boosting with protein approach. However, the novelty of the approach utilized
      in this study is that both the DNA priming and protein boosting was performed on
      a single day and no further vaccine inoculations were given to mice; the animals
      were challenged 1 month after the initial vaccine administration. Using this
      approach, significant reduction in worm burden (33 to 57 %) and marked decrease
      in egg retention in tissues (34 to 66%) was observed. Robust antibody titers and
      upregulation of cytokines (IL-1alpha/beta, IL-12alpha, and IFN-gamma) appears to
      correlate with the protection. This approach of administering vaccine on a single
      day could be greatly helpful in the field setting because it will eliminate the
      compliance issues that may arise with multiple boosters that may be required for
      optimal efficacy for some vaccines.

PMID- 24452917
TI  - Impact of mechanical disturbance on the emergence of Culicoides from cowpats.
AB  - The outbreaks of Bluetongue virus and Schmallenberg virus between 2006 and 2012
      highlighted the need for control methods for north-western Palaearctic biting
      midge species. There is especially a demand for alternative control methods
      without application of insecticides. Therefore, the objective of this paper was
      to evaluate the impact of mechanical disturbance as a control method for
      Culicoides biting midges in cowpats. We used a trash rake to destroy the compact
      structure of cowpats and spread the dung over the ground. We expected the
      disturbance to cause a faster alteration of physical characteristics and drying
      of the dung, resulting in lower emergence from disturbed cowpats. Emerging biting
      midges were collected with emergence traps. The number of emerged Culicoides was
      compared between treated and control cowpats. A total of 12,979 biting midges
      emerged, all belonging to the Obsoletus group. The majority of the 6,758 male
      individuals were identified as Culicoides chiopterus (Meigen, 1830) (91.4%),
      followed by Culicoides dewulfi (Goetghebuer, 1936) (6.5%), and a small number of
      Culicoides scoticus (Downes & Kettle, 1952) (1.2%). Our results showed no
      significant differences between the emergence of Culicoides (males and females)
      from disturbed and control cowpats. The lack of differences is discussed in light
      of the time period chosen for the experiment and the climatic conditions
      (especially low temperatures) during the study period. The climatic conditions
      during the study did not favour desiccation effects and therefore did not cause a
      severe alteration of the dung and the biotic parameters. In conclusion, immature
      Culicoides showed a high tolerance against mechanical disturbance.

PMID- 24452919
TI  - "Shaken baby syndrome" and forensic pathology.

PMID- 24452918
TI  - Comparative evaluation of Schistosoma mansoni, Schistosoma intercalatum, and
      Schistosoma haematobium alkaline phosphatase antigenicity by the alkaline
      phosphatase immunoassay (APIA).
AB  - To know if alkaline phosphatase (AP) from schistosomes other than Schistosoma
      mansoni can be used as diagnostic marker for schistosomiasis in alkaline
      phosphatase immunocapture assay (APIA), we comparatively tested n-butanol
      extracts of adult worm membranes from a Venezuelan (JL) strain of S. mansoni
      (Ven/AWBE/Sm); a Cameroonian (EDEN) strain of Schistosoma intercalatum
      (Cam/AWBE/Si) and a Yemeni strain of Schistosoma haematobium (Yem/AWBE/Sh). APIA
      was evaluated with sera of patients from Venezuela, Senegal, and Gabon infected
      with S. mansoni, from Gabon infected with S. intercalatum or S. haematobium, from
      Chine infected with Schistosoma japonicum and from Cambodian patients infected
      with Schistosoma mekongi. Results indicate that 92.5% (37/40) of Venezuela sera,
      75% (15/20) of Senegal sera, 39.5% (17/43) of S. haematobium sera, and 19.2%
      (5/26) S. intercalatum sera were APIA-positive with the Ven/AWBE/Sm preparation.
      APIA with the Cam/AWBE/Si preparation showed that 53.8% of S. intercalatum
      positive sera had anti-AP antibodies, and 51.2% S. haematobium-positive sera
      cross-immunocapturing the S. intercalatum AP. APIA performed with Yem/AWBE/Sh
      showed that 55.8% S. haematobium sera were positive. Only two out of nine S.
      japonicum sera were APIA-positive with the Ven/AWBE/Sm and Cam/AWBE/Si, and no
      reaction was observed with Cambodian S. mekongi-positive sera. AP activity was
      shown to be present in all the schistosome species/strains studied. The use of
      APIA as a tool to explore the APs antigenicity and the presence of Schistosoma
      sp. infections through the detection of anti-Schistosoma sp. AP antibodies in a
      host, allowed us to demonstrate the antigenicity of APs of S. mansoni, S.
      intercalatum, and S. haematobium.

PMID- 24452920
TI  - Preventive pathology revisited.

PMID- 24452921
TI  - Prevalence and impact of fall-risk-increasing drugs, polypharmacy, and drug-drug
      interactions in robust versus frail hospitalised falls patients: a prospective
      cohort study.
AB  - BACKGROUND: Several measures of medication exposure are associated with adverse
      outcomes in older people. Exposure to and the clinical outcomes of these measures
      in robust versus frail older inpatients are not known. OBJECTIVE: In older robust
      and frail patients admitted to hospital after a fall, we investigated the
      prevalence and clinical impact of fall-risk-increasing drugs (FRIDs), total
      number of medications, and drug-drug interactions (DDIs). METHODS: Patients >=60
      years of age admitted with a fall to a tertiary referral teaching hospital in
      Sydney were recruited and frailty was assessed. Data were collected at admission,
      discharge, and 2 months after admission. RESULTS: A total of 204 patients were
      recruited (mean age 80.5 +/- 8.3 years), with 101 robust and 103 frail. On
      admission, compared with the robust, frail participants had significantly higher
      mean +/- SD number of FRIDs (frail 3.4 +/- 2.2 vs. robust 1.6 +/- 1.5, P <
      0.0001), total number of medications (9.8 +/- 4.3 vs. 4.4 +/- 3.3, P < 0.0001),
      and DDI exposure (35 vs. 5 %, P = 0.001). Number of FRIDs on discharge was
      significantly associated with recurrent falls [odds ratio (OR) 1.7 (95 %
      confidence interval [CI] 1.3-2.1)], which were most likely to occur with 1.5
      FRIDs in the frail and 2.5 FRIDs in the robust. Number of medications on
      discharge was also associated with recurrent falls [OR 1.2 (1.0-1.3)], but DDIs
      were not. CONCLUSION: Exposure to FRIDs and other measures of high-risk
      medication exposures is common in older people admitted with falls, especially
      the frail. Number of FRIDs and to a lesser extent total number of medicines at
      discharge were associated with recurrent falls.

PMID- 24452922
TI  - Nematicidal activity of fluensulfone against some migratory nematodes under
      laboratory conditions.
AB  - BACKGROUND: The fluoroalkenyl fluensulfone, known to have strong nematicidal
      activity against Meloidogyne spp. (root-knot nematodes), was evaluated in vitro
      and in soil against the migratory nematodes Bursaphelenchus xylophilus,
      Aphelenchoides besseyi, Aphelenchoides fragariae, Ditylenchus dipsaci,
      Pratylenchus penetrans, Pratylenchus thornei and Xiphinema index. RESULTS: B.
      xylophilus and D. dipsaci were not immobilised by 48 h in vitro exposure to up to
      16 mg L(-1) of fluensulfone. A. besseyi and A. fragariae were affected by 8 mg L(
      1) , the highest concentration used for these nematodes. More than 60% of P.
      penetrans and P. thornei were immobilised by 4 mg L(-1) of fluensulfone; however,
      exposure of P. penetrans to the compound prior to inoculation did not affect
      their root penetration ability. The immobilisation rate of X. index was increased
      by 48 h exposure to even 1.0 mg L(-1) of fluensulfone. Incorporation of over 2 mg
      L(-1) of fluensulfone into the soil reduced populations of P. penetrans and P.
      thornei before and after planting lettuce and chickpea respectively. The efficacy
      of fluensulfone against the tested nematodes was the same or higher than that of
      fenamiphos in most cases. CONCLUSION: A. besseyi, A. fragariae, B. xylophilus and
      D. dipsaci were tolerant to fluensulfone and fenamiphos. P. penetrans, P. thornei
      and X. index were affected by fluensulfone, but nematicidal activity was much
      lower than that reported for root-knot nematodes.

PMID- 24452923
TI  - Procedural and follow-up outcomes among patients undergoing successful
      recanalisation of coronary chronic total occlusions using biolimus drug-eluting
      stents.
AB  - This study aimed at evaluating the outcome of Biolimus eluting stent (BES)
      implantation in the treatment of chronic total coronary occlusions (CTO). We
      identified patients who underwent successful angioplasty for a CTO lesion with
      >=1 BES between June 2008 and March 2012. All patients were followed up for major
      adverse cardiac events (MACE), which comprised death, non-fatal myocardial
      infarction (MI), cerebrovascular accident, target vessel revascularization (TVR),
      target lesion revascularization (TLR) and stent thrombosis. 125 patients
      underwent successful CTO angioplasty with >=1 Biolimus-eluting stents. Mean age
      was 63.8 +/- 12.0 years, and 82.4 % were males. Lesion location was right
      coronary artery (n = 80, 64 %), left anterior descending artery (n = 35, 28 %)
      and left circumflex artery (n = 10, 8 %). During follow-up of 579 +/- 293 days,
      all cause mortality was n = 8 (6.4 %) patients, non-fatal MI was n = 3 (2.4 %),
      TVR was n = 3 (2.4 %) and TLR was n = 1 (0.8 %). Overall MACE was, therefore, n =
      15 (12 %). BES is safe and effective in treatment of CTO lesions, with a low rate
      of major adverse cardiovascular events during follow-up. 

PMID- 24452924
TI  - Top-down proteomics: enhancing 2D gel electrophoresis from tissue processing to
      high-sensitivity protein detection.
AB  - The large-scale resolution and detection of proteins from complex native mixtures
      is fundamental to quantitative proteomic analyses. Comprehensive analyses depend
      on careful tissue handling and quantitative protein extraction and assessment. To
      most effectively link these analyses with an understanding of underlying
      molecular mechanisms, it is critical that all protein types - isoforms, splice
      variants and those with functionally important PTMs - are quantitatively
      extracted with high reproducibility. Methodological details concerning protein
      extraction and resolution using 2DE are discussed with reference to current in
      gel protein detection limits. We confirm a significant increase in total protein,
      and establish that extraction, resolution and detection of phospho- and
      glycoproteins are improved following automated frozen disruption relative to
      manual homogenisation. The quality of 2DE protein resolution is established using
      third-dimension separations and 'deep imaging'; substantially more
      proteins/protein species than previously realised are actually resolved by 2DE.
      Thus, the key issue for effective proteome analyses is most likely to be
      detection, not resolution. Thus, these systematic methodological and technical
      advances further solidify the role of 2DE in top-down proteomics. By routinely
      assessing as much proteomic data from a sample as possible, 2DE enables more
      detailed and critical insights into molecular mechanisms underlying different
      physiological states. 

PMID- 24452925
TI  - Water uptake, distribution, and mobility in amorphous poly(D,L-lactide) by
      molecular dynamics simulation.
AB  - An explicit all-atom computational model for amorphous poly(lactide) (PLA) was
      developed. Molecular dynamics simulations of PLA glasses were conducted to
      explore various molecular interactions and predict certain physical properties.
      The density of a newly formed PLA glass aged for 100 ns at 298 K was 1.23
      g/cm(3), close to the experimental range (1.24-1.25 g/cm(3)). The glass
      transition temperature (Tg = 364 K) was higher than experimental values because
      of the fast cooling rate (0.03 K/ps) in the simulation. The solubility parameter
      (20.6 MPa(1/2)) compared favorably to the literature. The water sorption isotherm
      obtained by relating the excess chemical potential of water in PLA to the Henry's
      law constant for water sorption was close to the experiment. At 0.6% (w/w), water
      molecules localize next to polar ester groups in PLA because of hydrogen bonding.
      Local mobility in PLA as characterized by the atomic fluctuation was sharply
      reduced near the Tg , decreasing further with aging at 298 K. The non-Einsteinian
      diffusion of water was found to correlate with the rotational beta-relaxation of
      PLA C=O groups at 298 K. A relaxation-diffusion coupling model proposed recently
      by the authors gave a diffusion coefficient (1.3 * 10(-8) cm(2) /s at 298 K)
      which is comparable to reported experimental values.

PMID- 24452927
TI  - A multiplex single nucleotide polymorphism genotyping method using ligase-based
      mismatch discrimination and CE-SSCP.
AB  - Accuracy, simplicity, and cost-effectiveness are the most important criteria for
      a genotyping method for SNPs compatible with clinical use. One method developed
      for SNP genotyping, ligase-based discrimination, is considered the simplest for
      clinical diagnosis. However, multiplex assays using this method are limited by
      the detection method. Although CE has been introduced as an alternative to error
      prone microarray-based detection, the design process and multiplex assay
      procedure are complicated because of the DNA size-dependent separation principle.
      In this study, we developed a simple and accurate multiplex genotyping method
      using reaction condition-optimized ligation and high-resolution CE-based SSCP.
      With this high-resolution CE-SSCP system, we are able to use similar-sized
      probes, thereby eliminating the complex probe design step and simplifying the
      optimization process. We found that this method could accurately discriminate
      single-base mismatches in SNPs of the tp53 gene, used as targets for multiplex
      detection.

PMID- 24452926
TI  - Near-infrared-light-mediated imaging of latent fingerprints based on molecular
      recognition.
AB  - Photoluminescence is one of the most sensitive techniques for fingerprint
      detection, but it also suffers from background fluorescence and selectivity at
      the expense of generality. The method described herein integrates the advantages
      of near-infrared-light-mediated imaging and molecular recognition. In principle,
      upconversion nanoparticles (UCNPs) functionalized with a lysozyme-binding aptamer
      were used to detect fingerprints through recognizing lysozyme in the fingerprint
      ridges. UCNPs possess the ability to suppress background fluorescence and make it
      possible for fingerprint imaging on problematic surfaces. Lysozyme, a universal
      compound in fingerprints, was chosen as the target, thus simultaneously meeting
      the selectivity and generality criteria in photoluminescence approaches.
      Fingerprints on different surfaces and from different people were detected
      successfully. This strategy was used to detect fingerprints with cocaine powder
      by using UCNPs functionalized with a cocaine-binding aptamer. 

PMID- 24452928
TI  - Ligament-induced sacral fractures of the pelvis are possible.
AB  - Pelvic ring stability is maintained passively by both the osseous and the
      ligamentous apparatus. Therapeutic approaches focus mainly on fracture patterns,
      so ligaments are often neglected. When they rupture along with the bone after
      pelvic ring fractures, disrupting stability, ligaments need to be considered
      during reconstruction and rehabilitation. Our aim was to determine the influence
      of ligaments on open-book injury using two experimental models with body donors.
      Mechanisms of bone avulsion related to open-book injury were investigated. Open
      book injuries were induced in human pelves and subsequently investigated by
      anatomical dissection and endoscopy. The findings were compared to CT and MRI
      scans of open-book injuries. Relevant structures were further analyzed using
      plastinated cross-sections of the posterior pelvic ring. A fragment of the distal
      sacrum was observed, related to open-book injury. Two ligaments were found to be
      responsible for this avulsion phenomenon: the caudal portion of the anterior
      sacroiliac ligament and another ligament running along the ventral surface of the
      third sacral vertebra. The sacral fragment remained attached to the coxal bone by
      this second ligament after open-book injury. These results were validated using
      plastination and the structures were identified. Pelvic ligaments are probably
      involved in sacral avulsion caused by lateral traction. Therefore, ligaments
      should to be taken into account in diagnosis of open-book injury and subsequent
      therapy.

PMID- 24452929
TI  - Synthetic approaches to site selective deuterium incorporation in a novel CRTh2
      receptor antagonist clinical candidate.
AB  - Selection of acidic or basic reaction conditions, combined with appropriate
      temperatures, allowed for site selective direct incorporation of deuterium at
      multiple positions in the 7-azaindole-3-acetic acid CRTh2 receptor antagonist
      clinical candidate NVP-QAV680.

PMID- 24452930
TI  - Schley's inguinal hernia repair: a single unit's experience of a forgotten
      technique.
AB  - BACKGROUND: This study was done to assess the effectiveness of Schley's inguinal
      hernia repair. It is a retrospective study analysing the outcome of patients who
      received the said technique over a period of 1 year at our institution. The
      minimum and the maximum follow-up periods were 2 and 3 years. METHOD: The
      patients who underwent the above technique in 2011 were reviewed retrospectively
      in December 2013 by going through the hospital records and examining the patients
      in person. RESULTS: 105 patients had undergone surgery in 2011. The majority of
      them had right-sided hernias and were in 40-59 age group. Two cases of wound
      infection, one case of haematocele and one hernia recurrence were noted.
      Operating on the recurrent hernia was straightforward. CONCLUSION: Schley's
      inguinal hernia repair is an effective technique with favourable outcome.

PMID- 24452931
TI  - The intracellular carboxyl terminal domain of Vangl proteins contains plasma
      membrane targeting signals.
AB  - Vangl1 and Vangl2 are integral membrane proteins that play a critical role in
      establishing planar cell polarity (PCP) in epithelial cells and are required for
      convergent extension (CE) movements during embryogenesis. Their proper targeting
      to the plasma membrane (PM) is required for function. We created discrete
      deletions at the amino and carboxy termini of Vangl1 and monitored the effect of
      the mutations on PM targeting in Madin-Darby canine kidney cells. Our results
      show that the Vangl1 amino terminus lacks PM targeting determinants, and these
      are restricted to the carboxy terminus, including the predicted PDZBM motif at
      the C-terminus. 

PMID- 24452932
TI  - Nanocoating of single cells: from maintenance of cell viability to manipulation
      of cellular activities.
AB  - The chronological progresses in single-cell nanocoating are described. The
      historical developments in the field are divided into biotemplating,
      cytocompatible nanocoating, and cells in nano-nutshells, depending on the main
      research focuses. Each subfield is discussed in conjunction with the others,
      regarding how and why to manipulate living cells by nanocoating at the single
      cell level. 

PMID- 24452934
TI  - Nasal function alterations in OSA during nasal CPAP: an overly complex influence
      of humidification?

PMID- 24452933
TI  - Deventilation syndrome in severe COPD patients during long-term noninvasive
      mechanical ventilation: poor sleep pattern, hyperinflation, or silent chronic
      muscular fatigue?

PMID- 24452935
TI  - Corneal biomechanical characteristics in children with diabetes mellitus.
AB  - To compare the corneal biomechanical properties in children with type 1 diabetes
      mellitus (DM) and healthy children. In this cross-sectional study, the study and
      control groups were composed of 68 children with DM and 74 healthy children,
      respectively. The corneal hysteresis (CH), corneal resistance factor (CRF),
      Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated
      intraocular pressure (IOPcc) were measured with the ocular response analyzer
      (ORA). Associations between ocular and diabetic parameters were also evaluated.
      There were no statistically significant differences between the two groups in age
      or gender distribution. The mean CH was 10.8 +/- 1.5 and 10.7 +/- 1.7 mmHg while
      the mean CRF was 10.9 +/- 1.9 and 10.5 +/- 1.6 mmHg in the diabetic group and
      control group, respectively. The mean IOPg was 15.9 +/- 3.7 and 15.2 +/- 3.4
      mmHg, and the mean IOPcc was 15.8 +/- 3.0 and 15.3 +/- 3.4 mmHg in the diabetic
      and control group, respectively. There were no statistically significant
      differences between the two groups for CH, CRF, IOPg, and IOPcc measurements
      (independent t test, p = 0.624, p = 0.207, p = 0.263, p = 0.395, respectively).
      This study shows that type 1 DM does not have any effect on the corneal
      biomechanical parameters in childhood.

PMID- 24452936
TI  - Impact of R&D expenditures on research publications, patents and high-tech
      exports among European countries.
AB  - OBJECTIVES: This study aimed to compare the impact of Research&Development (R&D)
      expenditures on research publications, patents and high-tech exports among
      European countries. MATERIALS AND METHODS: In this study, 47 European countries
      were included. The information regarding European countries, their per capita
      Gross Domestic Product (GDP), R&D spending, number of universities, indexed
      scientific journals, high technology exports and number of patents were
      collected. We recorded the total number of research documents in various science
      and social sciences subjects during the period 1996-2011. The main source for
      information was World Bank, Web of Science, Thomson Reuters and SCImago/Scopus.
      RESULTS: The mean GDP per capita for all the European countries is 23372.64 +/-
      3588.42 US$, yearly per capita spending on R&D 1.14 +/- 0.13 US$, number of
      universities 48.17 +/- 10.26, mean number of Institute of Scientific Information
      (ISI) indexed journal per country 90.72 +/- 38.47, high technology exports 12.86
      +/- 1.59 and number of patent applications 61504.23 +/- 22961.85. The mean of
      research documents published in various science and social science subjects among
      all the European countries during the period 1996-2011 is 213405.70 +/- 56493.04.
      Spending on R&D, number of universities, indexed journals, high technology
      exports and number of patents have a positive correlation with number of
      published documents in various science and social science subjects. We found a
      positive correlation between patent application and high-tech exports. However,
      there was no association between GDP per capita and research outcomes.
      CONCLUSIONS: It is concluded that, the most important contributing factors
      towards a knowledge based economy are spending on R&D, number of universities,
      scientific indexed journals and research publications, which in turn give a boast
      to patents, high technology exports and ultimately GDP.

PMID- 24452937
TI  - Effect of etanercept and lithium chloride on preventing secondary tissue damage
      in rats with experimental diffuse severe brain injury.
AB  - OBJECTIVE: Studies in animals have provided key evidence that antagonizing TNF
      alpha is a viable therapeutic strategy for diffuse severe brain injury. This
      study is planned to prevent post-traumatic secondary tissue damages in rat
      diffuse severe brain injury model, which is induced by alone or combined
      administration of Etanercept and lithium chloride (LiCl). MATERIALS AND METHODS:
      Male Sprague-Dawley rats were used in the current study. Rats were divided into 5
      groups. Trauma was not induced and treatment was not applied to rats of Sham
      group. For rats of Trauma+Saline group, saline 0.9% was administered via
      intraperitoneal (i.p.) route at dose of 1 mg/100 g body weight 1 hour after
      trauma. For rats of Trauma+Etanercept group, Etanercept was administered via i.p.
      route at dose of 5 mg/kg body weight 1 hour after trauma. For rats of Trauma+LiCl
      group, LiCl was administered via i.p. route at dose of 50 mg/kg body weight 1
      hour after trauma. For rats of Etanercept+LiCl group, Etanercept and LiCl were
      administered via i.p. route at dose of 5 mg/kg body weight and 50 mg/kg body
      weight, respectively, 1 hour after trauma. Serum glial fibrillary acidic protein
      (GFAP) and Tau levels were analyzed with ELISA. For analyses H&E, TUNEL, GFAP and
      TNF-alpha staining methods were used. RESULTS: We demonstrate that Etanercept
      treatment reduced the TBI-induced brain tissues alteration, reduced the
      expression of TNF-alpha and improve edema and axonal swelling. We observed a
      significant decrease in TNF-alpha and GFAP positivity after LiCl was
      administered. CONCLUSIONS: The findings obtained in this study suggest that the
      combination therapy with Etanercept and LiCl decreased neuronal degeneration and
      alleviated secondary tissue damage in post-traumatic period.

PMID- 24452938
TI  - Rat embryo exposure to all-trans retinoic acid results in long-term cognitive
      deficits.
AB  - AIM: The present study examines in particular associative learning and aversive
      memory abilities in adult Sprague Dawley rats exposed to all-trans retinoic acid
      (ATRA) in the period spanning gestational days (GD) 11-13. MATERIALS AND METHODS:
      The ATRA dosage of 2.5 mg/kg compatible with high neonatal survival, sufficient
      to supply offspring for later behavioral testing, was used. RESULTS: The results
      show that the GD 11-13 ATRA exposure compromises the ability of rats to learn an
      active avoidance task. Indeed, unlike control rats, the ATRA-treated rats did not
      improve in performance over blocks of training, the number of attempts they made
      to avoid foot shock being significantly affected. The memory ability, assessed
      with the passive avoidance paradigm, was not affected by ATRA exposure.
      CONCLUSIONS: The results provide further evidence that, beyond gross CNS
      malformations, gestational ATRA exposure induces long-term cognitive deficits in
      the offspring, thus raising further warning for better control of retinoid safety
      during pregnancy, an aspect relevant to human health protection within the
      regulatory environment.

PMID- 24452939
TI  - Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose)
      polymerase in distant liver injury induced by renal ischemia-reperfusion in rats.
AB  - BACKGROUND AND AIMS: Renal ischemia followed by reperfusion causes remote liver
      injury. This research was planned to investigate whether 3-aminobenzamide (3-AB),
      has any preventive effect against distant liver injury triggered by renal IR.
      MATERIALS AND METHODS: Twenty four rats were randomly divided into three
      different groups Each group has 8 rats. The groups were as follows: (1) Sham
      operated group; (2) Renal ischemia-reperfusion (IR) group; (3) Renal IR+ 3-AB
      group. 3-AB (10 mg/kg) was given intraperitoneally 10 minute before reperfusion.
      At the end of study, the rats were sacrificed. Their liver tissues and serum
      samples were collected for measurement of malondialdehyde (MDA) levels, total
      oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1)
      activity and nitric oxide (NO). RESULTS: Renal IR injury significantly increased
      Oxidative stress index (OSI) and MDA, TOS levels and significantly decreased PON
      1 actvity and TAS, NO levels in serum and liver tissue (p < 0.05). Despite that,
      changes in these biochemical parameters related with IR injury were diminished by
      3-AB administration (p < 0.05). CONCLUSIONS: The inhibition of PARP [Poly(ADP
      Ribose)Polymerase] by 3-AB showed protective effects against distant liver injury
      triggered by renal ischemia-reperfusion by the ameliorating effects of 3-AB on
      oxidative stress.

PMID- 24452940
TI  - Endothelial constitutive nitric oxide synthase, angiotensin converting enzyme,
      angiotensin II type 1 receptor gene polymorphisms and endothelial functions in
      healthy individuals.
AB  - INTRODUCTION: Endothelial dysfunction is recognized as an early and initiating
      event in the pathogenesis of coronary artery disease. Gene polymorphisms of
      endothelial constitutive nitric oxide synthase (ecNOS), angiotensin converting
      enzyme (ACE) and angiotensin II type 1 receptor (AT1R) have been found to be
      associated with atherosclerosis.  We aimed to investigate the possible effects of
      ecNOS, ACE and AT1R gene polymorphisms on endothelial functions in healthy
      population. MATERIALS AND METHODS: In 255 healthy subjects (male/female: 119/136
      mean age 35.1+/-2.3 years)  ecNOS, ACE and AT1R gene polymorphisms were assessed
      by polymerase chain reaction (PCR). Endothelium dependent (EDD, flow-mediated)
      and endothelium independent vasodilation (EID) were measured by high resolution
      brachial artery ultrasound and 0.5 mg sublingual nitroglycerine respectively.
      RESULTS: ecNOS and ACE genes had no significant effect on EDD and EID. However,
      subjects with AT1RAC+CC genotypes had lower EDD compared to subjects with AT1RAA
      genotype in females (19.4 +/- 6.6% vs 21.5 +/- 7.8%, p = 0.041). EDD and EID were
      significantly negatively associated with  age, body mass index, serum creatinine,
      glucose, uric acid and hemoglobin levels. When the data on age, uric acid, BMI,
      glucose, creatinine, and hemoglobin were split into 3 as low-1/3, mid-1/3 and 
      high 1/3, there was significant graded decrease in EDD and EID with these
      parameters. In multiple regression analysis, age and presence of AT1RAC+CC
      genotype  retained as significant independent factors predicting endothelial
      functions. CONCLUSIONS: Gene polymorphisms of endothelial constitutive nitric
      oxide synthase and  angiotensin converting enzyme had no effect on endothelial
      functions. However, the presence of angiotensin II type 1 receptor polymorhism
      (AT1RAC+CC genotype) seemed to adversely affect the endothelial functions as
      reflected by impaired endothelium dependent and independent vasodilatation in
      healthy individuals.

PMID- 24452942
TI  - Screening of genes related to acute coronary syndrome and identification of
      functional modules in the PPI network.
AB  - BACKGROUND: Acute coronary syndrome (ACS), referring to any group of symptoms
      attributed to obstruction of the coronary arteries, affects millions of patients
      annually and requires immediate diagnosis and therapy. OBJECTIVE: The purpose of
      this study was to find more biomarkers through identifying the genes which are
      related to ACS with samples from normal and diseased blood vessel. MATERIALS AND
      METHODS: We downloaded the gene expression profile of GSE19339 from GEO (Gene
      Expression Omnibus) database, including 4 samples for normal and 4 for ACS. Then,
      the preprocessing of the data and analysis of differentially expressed genes
      (DEGs) were conducted with R language. WebGestalt was used to analyze the
      functions of the DEGs and STRING was applied to build the protein-protein
      interaction (PPI) network. At last, we used two plugins of Cytoscape to map the
      functional modules on the base of the PPI network. RESULTS: A total of 480 genes
      were identified as DEGs between normal and disease samples, which were most
      significantly related to blood vessel development. After the partition of the PPI
      network, we got two functional modules, and CD, CXCL, CCL and ICAM1 genes were
      found served as the nodes of the two modules. These genes were all related to the
      immune response system. CONCLUSIONS: Our present findings suggest that CD, CXCL,
      CCL and IL genes may be used as biomarkers in the research of ACS and the immune
      response system may also play an important role in the pathogenesis of ACS.
      However, further experiments are still needed to confirm our result.

PMID- 24452941
TI  - Effect of bauhinia bauhinioides kallikrein inhibitor on endothelial proliferation
      and intracellular calcium concentration.
AB  - OBJECTIVES: Proteinase inhibitors act as a defensive system against predators
      e.g. insects, in plants. Bauhinia bauhinioides kallikrein inhibitor (BbKI) is a
      serine proteinase inhibitor, isolated from seeds of Bauhinia bauhinioides and is
      structurally similar to plant Kunitz-type inhibitors but lacks disulfide bridges.
      In this study we evaluated the antiproliferative effect of BbKI on endothelial
      cells and its impact on changes in membrane potential and intracellular calcium.
      MATERIALS AND METHODS: HUVEC proliferation was significantly reduced by
      incubation with BbKI 50 and 100 uM 12% and 13%. Furthermore, BbKI (100 uM)
      exposure caused a significant increase in intracellular Ca2+ concentration by 35%
      as compared to untreated control. RESULTS: The intracellular rise in calcium was
      not affected by the absence of extracellular calcium. BBKI also caused a
      significant change in the cell membrane potential but the antiproliferative
      effect was independent of changes in membrane potential. CONCLUSIONS: BBKI has an
      antiproliferative effect on HUVEC, which is independent of the changes in
      membrane potential, and it causes an increase in intracellular Ca2+.

PMID- 24452943
TI  - The influence of antihypertensive drugs on mineral status in hypertensive
      patients.
AB  - OBJECTIVES: Long-term therapy of hypertension may influence mineral status in
      patients. However, drug-micronutrient interactions are largely unexplored in
      practice. This study intended to evaluate the effect of hypotensive monotherapy
      on iron, zinc, and copper levels, as well as on selected biochemical parameters,
      in newly diagnosed patients with hypertension, and to assess the influence of
      diet with optimal mineral levels on the mineral balance in these subjects.
      PATIENTS AND METHODS: Forty-five patients, aged 18-65 years with diagnosed
      essential hypertension, beginning monotherapy treatment with diuretics, calcium
      antagonists, angiotensin-converting enzyme inhibitors, and beta-blockers, were
      employed. Over three months, the patients underwent monotherapy (stage II). Next,
      patients were randomly divided into a diet group (of 27 subjects) and a control
      group (of 18 subjects). In this stage, which lasted one month, patients were
      given the same drug but also followed an optimal mineral-content diet (for the
      diet group), or else continued drug use without any change in diet (for control
      group) (stage III). Lipids, glucose, ceruloplasmin, and ferritin--along with
      superoxide dismutase and catalase activities--were assayed in serum. Iron, zinc,
      and copper concentrations in serum, erythrocytes, and urine were determined using
      flame atomic absorption spectrometry. Blood pressure was measured. Diet intake
      was monitored at each stage. RESULTS: It was found that the zinc level in serum
      significantly decreased following treatment, and that the use of the optimal
      mineral diet during antihypertensive treatment markedly increased zinc serum
      concentration. After treatment, a significant increase in zinc excretion in the
      urine was observed. Glucose levels in the serum of patients in stage II were
      significantly higher than in the baseline. In patients in the diet group, glucose
      levels markedly decreased. Moreover, a negative correlation was found between
      serum glucose and zinc levels in patients. CONCLUSIONS: Antihypertensive
      treatments should include monitoring of mineral status. It seems that the zinc
      balance of patients on long-term therapy with hypotensive drugs may benefit from
      an optimal-mineral diet.

PMID- 24452944
TI  - Predictors of reintervention after coronary artery bypass grafting.
AB  - AIM: Percutaneous and surgical reintervention after coronary artery bypass
      grafting (CABG) is frequent. The purpose of this study was to determine the
      predictors of reintervention in patients with symptoms of recurrent ischemia
      after coronary artery bypass graft surgery (CABG). PATIENTS AND METHODS: The data
      of 20000 patients who had coronary angiography (CAG) from 2003 to 2010 in our
      centre were retrospectively analysed. 485 of these patients with CABG who had CAG
      were included in this study. Demographic characteristics, the presence of
      coronary artery disease (CAD), risk factors for CAD, electrocardiographic (ECG)
      changes, troponin and CKMB levels, and left ventricular function were evaluated
      in terms of time elapsed after CABG. RESULTS: Reintervention was performed
      significantly more frequent in patients with acute coronary syndrome, diabetes
      mellitus (DM), hypertension (HT), family history of CAD, ECG changes, positive
      troponin level, elevated CKMB, ejection fraction (EF) > 50% and in smoker
      patients (p < 0.05). Multivariate backward logistic regression analysis revealed
      that DM, smoking, family history of CAD, HT, ECG changes and patients with EF >
      50% were found the independent predictors of reintervention. CONCLUSIONS:
      Reintervention after CABG is especially higher in patients with risk factors for
      atherosclerosis and those who have ECG changes and normal EF. Knowledge of these
      risk factors is useful in the determination of CAG requirement and modification
      of risk factors for  atherosclerosis may play an important role in reducing
      reintervention.

PMID- 24452945
TI  - Twin left circumflex arteries in a patient undergoing aortic valve replacement.
AB  - We present the case of a patient with severe symptomatic aortic valve (AV)
      stenosis in whom preoperative coronary angiography revealed two separate left
      circumflex (LCx) arteries, one arising from the left main coronary artery and the
      other from the right aortic sinus following thereafter a retroaortic course to
      the left. The pattern of LCx artery anatomy revealed was recognized as one of
      bilaterally arising twin LCx arteries that is a rare coronary anomaly with only 7
      reported cases in the English literature. We discuss the importance of
      preoperative identification of this anomaly in patients undergoing AV surgery and
      describe simple clues in order to easily identify it. 

PMID- 24452946
TI  - The role of 3D and speckle tracking echocardiography in cardiac amyloidosis: a
      case report.
AB  - Cardiac amyloidosis (CA) is a disorder characterized by amyloid fibrils
      deposition in cardiac interstitium; it results in a restrictive cardiomyopathy
      with heart failure (HF) and conduction abnormalities. The "gold standard" for
      diagnosis of CA is myocardial biopsy but possible sampling errors and procedural
      risks, limit it's use. Magnetic resonance (RMN) offers more information than
      traditional echocardiography and allows diagnosis of CA but often it's impossible
      to perform. We report the case of a man with HF and symptomatic bradyarrhythmia
      that required an urgent pacemaker implant. Echocardiography was strongly
      suggestive of CA but wasn't impossible to perform an RMN to confirm this
      hypothesis because the patient was implanted with a definitive pacemaker. So was
      performed a Speckle Tracking Echocardiography (STE) and a 3D echocardiography:
      STE allows to differentiate CA from others hypertrophic cardiomyopathy by
      longitudinal strain value < 12% and 3D echocardiography shows regional left
      ventricular dyssynchrony with a characteristic temporal pattern of dispersion of
      regional volume systolic change. On the basis of these results, finally was
      performed an endomyocardial biopsy that confirmed the diagnosis of CA. This case
      underlines the importance of news, noninvasive techniques such as eco 3D and STE
      for early diagnosis of CA, especially when RMN cannot be performed. 

PMID- 24452948
TI  - Biomechanical assessment of a novel L4/5 level interspinous implant using three
      dimensional finite element analysis.
AB  - OBJECTIVES: Range of motion (ROM) is often restricted by conventional spinal
      fusion surgery, while some complications also occurred after applying posterior
      dynamic devices in clinic. Therefore, new surgical implant options were
      necessitated. The biomechanical features of a novel interspinous implant were
      investigated using three dimensional (3D) finite element models (FEMs). MATERIALS
      AND METHODS: An "H-shaped" polyether ether ketone (PEEK) interspinous implant was
      designed to tightly fit the upper and lower spinous processes, featuring a hollow
      cylindrical portion which was implanted autologous bones to enhance fusion with
      spinous processes. A 3D FEM of the intact L3/S segment with mild disc
      degeneration in L4/5 (degenerated model) was developed and subjected to flexion
      extension, lateral bending, and axial rotation either with or without the
      implanted prosthesis (implant model) in order to examine effects on ROM,
      intradiscal stress, and facet joint load. RESULTS: The whole lumbar ROM was
      altered slightly by implant insertion, and reduced end plate stress, nucleus
      stress, and facet joints load at the L4/5 level (implant location) were observed.
      L4/5 flexion-extension maximal end plate stress, nucleus stress, and facet joints
      load were 5.262 MPa, 0.1648 MPa, and 29.7 N, respectively, in the degenerated
      model and 2.323 MPa, 0.0892 MPa, and 5.4 N, respectively, in the implant model.
      End plate and nucleus stresses were partially alleviated at the L3/4 level.
      Slightly higher maximal von Mises stress in L3/4 and L5/S annuli were observed in
      the implant model. CONCLUSIONS: The proposed novel interspinous implant
      effectively restored stability without producing excessive ROM limitations,
      meriting further clinical evaluation. Furthermore, these findings provide a
      useful basis for wide application of FEM in a broad variety of spinal implant
      assessments.

PMID- 24452947
TI  - Increased apoptosis induction in CD4+ CD25+ Foxp3+ T cells contributes to
      enhanced disease activity in patients with rheumatoid arthritis through IL-10
      regulation.
AB  - BACKGROUND: Abnormality in the number and function of regulatory T cells (Tregs)
      has been linked to initiation and progression in patients with Rheumatoid
      Arthritis (RA). AIM: This study aims to demonstrate the apoptosis status of
      regulatory T cells (Tregs) and its correlation with clinical activity of RA
      patients and the effect of interleukin-10 (IL-10) on Tregs apoptosis in RA.
      MATERIALS AND METHODS: Apoptosis rates and its related molecules including Fas,
      Bcl-2, Caspase-3 and Caspase-8 were examined using flow cytometry. The
      correlation between the apoptosis level of Tregs and clinical activity parameters
      including ESR (erythrocyte sedimentation rate), CPR (C reactive protein), RF
      (Rheumatoid Factor) and DAS28 (Disease activity score 28) was analysed. PBMCs
      isolated from RA patients were cultured with IL-10 or anti-IL-10, and the
      apoptosis frequency of Tregs was then analyzed. RESULTS: The frequency of Tregs
      in active RA patients was decreased, and Fas, Caspase-3 and Caspase-8 expression
      on Tregs was much higher compared with the healthy subjects. The expression of
      anti-apoptotic protein, Bcl-2 on Tregs did not display significant changes
      between active RA patients and healthy subjects. There was a significantly
      positive correlation between the levels of apoptosis rates and Caspase-3
      expression in Tregs and DAS28 of active RA patients. The apoptosis rates of Tregs
      in RA patients decreased or increased, respectively, following treatment with IL
      10 or anti-IL-10 antibody in vitro. CONCLUSIONS: Apoptosis pathways are defective
      in Treg cells from RA patients with active disease. IL-10 treatment can modulate
      apoptosis in Tregs via extrinsic (type I) pathway, which may lead to restoration
      of the Tregs towards that of controlling autoimmune reaction in RA patients.

PMID- 24452949
TI  - The effect of bevacizumab and 5-Fluorouracil combination on epidural fibrosis in
      a rat laminectomy model.
AB  - OBJECTIVE: An animal model of laminectomy in rats was used to study scar tissue
      formation around the spinal cord. Bevacizumab (BV) [a recombinant, humanized,
      monoclonal antibody targeting vascular endothelial growth factor], 5-Fluorouracil
      (5-FU) and BV+5-FU was tested in this system for its ability to decrease fibrous
      tissue formation. MATERIALS AND METHODS: Twenty-eight Sprague Dawley rats were
      used in this sudy. Rats were divided into four groups; a control group, a BV
      group, a 5-FU group and a BV+5-FU group. L1-2 laminectomies were performed on the
      rats. The medicated groups were treated with topical drug administration. After 6
      weeks, the rats were sacrified and histologic sections prepared from the spines
      were examined and graded by a pathologist. Epidural fibrosis and fibroblast
      density were evaluated under light microscope. RESULTS: BV (Avastin: Genentech,
      San Francisco, CA, USA) significantly reduced the density of the scar tissue
      undermining the laminas (p < 0.005). Monotherapy with 5-FU did not change the
      scar formation in the back (p = 0.317). Combination of 5-FU and BV was more
      effective on reducing the epidural fibrosis after laminectomy on rats (p <
      0.001). CONCLUSIONS: Bevacizumab reduced the spinal epidural fibrosis
      significantly that developed in rats after laminectomy and 5-Fluorouracil
      combination had a synergic effect. Further investigations under the light of
      these findings may help to reduce epidural fibrosis formation after laminectomy.

PMID- 24452950
TI  - Bioinformatics analysis of gene expression profiles in the rat cerebral cortex
      following traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a serious neurodisorder commonly
      caused by sports related events or violence. It is the leading cause of
      disability in people under 40. AIM: In order to elucidate the molecular mechanism
      of the secondary injury after TBI. MATERIALS AND METHODS: In this study, we
      downloaded gene expression profile on TBI model with sham controls for gene set
      enrichment analysis and pathway analysis. RESULTS: At a q-value of 5%, 361 genes
      were up-regulated and 373 were down-regulated in samples obtained at 48 hours
      after TBI. Functional analyses revealed that steroid biosynthesis, cell cycle,
      metal ion transport, inflammation and apoptosis were significantly dysregulated
      during the late period after trauma. In addition, MAPK3 (mitogen-activated
      protein kinase 3), was identified as the hub node in the protein-protein
      interaction (PPI) network constructed by the differentially expressed genes
      (DEGs). CONCLUSIONS: Further elucidation of genes and proteins in our study may
      reveal their potential as novel therapeutic targets.

PMID- 24452951
TI  - Identification of typical miRNAs and target genes in hepatocellular carcinoma by
      DNA microarray technique.
AB  - OBJECTIVES: The purpose of this study was to identify featured miRNAs of
      hepatocellular carcinoma (HCC) by comparing normal and cancer cell line samples
      and find potential utility as biomarkers for early diagnosis and treatment of
      HCC. MATERIALS AND METHODS: We downloaded the gene expression profile GSE41077
      from Gene Expression Omnibus database which included 6 HCC cell lines samples and
      2 controls. Differentially expressed miRNAs were identified by multtest package
      in R language after the data normalization. The selected differentially expressed
      miRNAs were further analyzed using bioinformatics methods. Target genes of these
      miRNAs were predicted using miRTarBase and miRecords databases. STRING software
      was used to construct the interaction network of target genes. Finally, we made
      module analysis by using Cytoscape software and its plugins--MCODE and BiNGO.
      RESULTS: A total of 40 differentially expressed miRNAs were identified and the
      remarkably down-regulated miRNA was hsa-miR-122 which included 29 high confident
      target genes. The interaction network of target genes was constructed among 629
      interaction pairs. Four functional modules in the network were obtained, from
      which EGLN3, ALDOA, NCAM1 and AACS were the high confident target genes,
      respectively. Genes in the modules most related to biological functions of signal
      transmission, regulation of macromolecule metabolic process. CONCLUSIONS: Low
      level of expression of hsa-miR-122 in HCC cell line is consistent with the
      existed previous studies. It is not only confirm the importance role of such
      miRNA in HCC cells, but also provide important help in identifying specific
      biomarker of HCC cells.

PMID- 24452952
TI  - Screening of genes related to lung cancer caused by smoking with RNA-Seq.
AB  - AIM: To study the lung cancer caused by smoking from RNA-seq data and its
      mechanism at molecular level. MATERIALS AND METHODS: We downloaded gene
      expression profile SRA (Sequence Read Archive) data from Gene Expression Omnibus
      database that included two samples: one was lung cancer tissue samples from
      smoker (GSM718710) and the other was from non-smoker (GSM718709). We analyzed
      differential expression of genes with packages software TopHat and Cufflinks, and
      did Gene Ontology (GO) function clustering of the differentially expressed genes
      by BLASTX. Then we utilized KEGG Orthology Based Annotation System (KOBAS) to
      make pathway annotation and do enrichment analysis of KEGG pathway. After that,
      we searched for probable alternative splicing of the selected differentially
      expressed genes and found closely-linked genes. RESULTS: we screened 1603
      differentially expressed genes, most of which were involved in cellular
      processes. We also identified that the possible alternative splicing of gene
      FCGBP might have an important impact on lung cancer. CONCLUSIONS: These findings
      in this study may help better understand the relationship between smoking and
      lung cancer pathogenesis.

PMID- 24452953
TI  - Effects of chemotherapy on global gene expression in non-small cell lung cancer.
AB  - INTRODUCTION: Gene expression profiles of peripheral blood monocytes from
      patients with non-small cell lung cancer (NSCLC) before and after chemotherapy
      were used to investigate the effect of chemotherapy on gene expression. MATERIALS
      AND METHODS: Microarray dataset GSE39345 was downloaded from Gene Expression
      Omnibus, including 32 NSCLC samples before chemotherapy, 17 NSCLC samples after
      chemotherapy and 20 healthy samples. Raw data pretreatment and differentially
      expressed genes (DEGs) analysis between health and NSCLC samples before
      chemotherapy, health and NSCLC samples after chemotherapy were performed with
      packages of R. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment
      analysis was done for the common DEGs with WebGestalt to investigate their
      underlying function. RESULTS: A total of 904 DEGs were identified in health vs.
      NSCLC samples before chemotherapy and 2148 in health vs. NSCLC samples after
      chemotherapy. Further, they were divided into three sets: 584 common DEGs, 320
      unique DEGs (health vs NSCLC samples before chemotherapy), and 1564 unique DEGs
      (health vs NSCLC samples after chemotherapy). Function enrichment analysis showed
      that these common DEGs were associated with cell cycle and cell differentiation.
      CONCLUSIONS: Chemotherapy could not completely reverse the lung cancer
      development because several cell growth-related genes are still present even
      after chemotherapy.

PMID- 24452954
TI  - Exploring the potential mechanism and screening small molecule drugs for glaucoma
      by using bioinformatics approach.
AB  - BACKGROUND: Glaucoma is a neurodegenerative disease which is the second most
      common cause of blindness worldwide. AIM: To investigate the mechanism of
      glaucoma and identify small molecule drugs. MATERIALS AND METHODS: Gene
      expression profiles of GSE2378 were downloaded from Gene Expression Omnibus (GEO)
      database which included 15 astrocytes from 8 and 7 donors with and without
      glaucoma, respectively. Then the raw data were normalized by Robust Multichip
      Averaging and the differentially expressed genes (DEGs) were identified with
      limma package in R. Moreover, the Gene Ontology and pathway enrichment analyses
      were performed by GOEAST and Gene Set Analysis Toolkit V2, respectively. In
      addition, the potential target sites of transcription factors were detected using
      MSigDB. Finally, small molecule drugs were screened for glaucoma treatment by
      Connectivity Map. RESULTS: A total of 961 DEGs between glaucoma and normal cells
      were identified. These DEGs were discovered mainly involved in cell surface,
      molecule binding, changes in protein activity and signal transduction.
      Additionally, the most significant pathway was pathway in cancer (FDR = 0.0051).
      Some DEGs shared target sites of the transcription factor, such as NFkappaB. (FDR
      = 0.0132) and PBX1 (FDR = 0.0158). Luteolin (enrichment = 0.87) can simulate the
      state of normal cells, while vancomycin (enrichment = -0.883) and Prestwick-1082
      (enrichment = -0.882) might be potential pathogenic substances. CONCLUSIONS: We
      hypothesize that glaucoma cells may be not only caused by the optic nerve cells
      themselves, but also caused by infections due to resistance decline. All these
      results may facilitate glaucoma treatment with a new breakthrough.

PMID- 24452955
TI  - The neutrophil lymphocyte ratio in patients with ST segment elevation myocardial
      infarction.

PMID- 24452956
TI  - Lipid levels in patients with Behcet's disease.

PMID- 24452958
TI  - Potential effects of environmental chemical contamination in congenital heart
      disease.
AB  - There is compelling evidence that prenatal exposures to environmental xenobiotics
      adversely affect human development and childhood. Among all birth defects,
      congenital heart disease (CHD) is the most prevalent of all congenital
      malformations and remains the leading cause of death. It has been estimated that
      in most cases the causes of heart defects remain unknown, while a growing number
      of studies have indicated the potential role of environmental agents as risk
      factors in CHD occurrence. In particular, maternal exposure to chemicals during
      the first trimester of pregnancy represents the most critical window of exposure
      for CHD. Specific classes of xenobiotics (e.g. organochlorine pesticides, organic
      solvents, air pollutants) have been identified as potential risk factors for CHD.
      Nonetheless, the knowledge gained is currently still incomplete as a consequence
      of the frequent heterogeneity of the methods applied and the difficulty in
      estimating the net effect of environmental pollution on the pregnant mother. The
      presence of multiple sources of pollution, both indoor and outdoor, together with
      individual lifestyle factors, may represent a further confounding element for
      association with the disease. A future new approach for research should probably
      focus on individual measurements of professional, domestic, and urban exposure to
      physical and chemical pollutants in order to accurately retrace the environmental
      exposure of parents of affected offspring during the pre-conceptional and
      pregnancy periods. 

PMID- 24452959
TI  - Comparison of non-invasive and invasive arterial blood pressure measurement for
      assessment of dynamic cerebral autoregulation.
AB  - BACKGROUND: There is a growing interest in measuring cerebral autoregulation in
      patients with acute brain injury. Non-invasive finger photo-plethysmography
      (Finapres) is the method of choice to relate arterial blood pressure to changes
      in cerebral blood flow. Among acutely ill patients, however, peripheral
      vasoconstriction often limits the use of Finapres requiring direct intravascular
      blood pressure measurement. We evaluated how these two different forms of blood
      pressure monitoring affect the parameters of dynamic cerebral autoregulation
      (DCA). METHODS: We performed 37 simultaneous recordings of BP and cerebral blood
      flow velocity in 15 patients with acute brain injury. DCA was estimated in the
      frequency domain using transfer function analysis to calculate phase shift, gain,
      and coherence. In addition the mean velocity index (Mx) was calculated for
      assessment of DCA in the time domain. RESULTS: The mean patient age was 58.1 +/-
      15.9 years, 80 % (n = 12) were women. We found good inter-method agreement
      between Finapres and direct intravascular measurement using Bland-Altman and
      correlation analyses. Finapres gives higher values for the efficiency of dynamic
      CA compared with values derived from radial artery catheter, as indicated by
      biases in the phase (26.3 +/- 11.6 degrees  vs. 21.7 +/- 10.5 degrees , p =
      0.001) and Mx (0.571 +/- 0.137 vs. 0.649 +/- 0.128, p < 0.001). Gain in the low
      frequency range did not significantly differ between the two arterial blood
      pressure methods. The average coherence between CBFV and ABP was higher when BP
      was measured with arterial catheter for frequencies above 0.05 Hz (0.8 vs. 0.73,
      p < 0.001). CONCLUSION: Overall, both methods yield similar results and can be
      used for the assessment of DCA. However, there was a small but significant
      difference for both mean Mx and phase shift, which would need to be adjusted for
      during monitoring of patients when using both methods. When available, invasive
      arterial blood pressure monitoring may improve accuracy and thus should be the
      preferred method for DCA assessment in the ICU.

PMID- 24452957
TI  - Na+/H+ exchangers and intracellular pH in perinatal brain injury.
AB  - Encephalopathy consequent on perinatal hypoxia-ischemia occurs in 1-3 per 1,000
      term births in the UK and frequently leads to serious and tragic consequences
      that devastate lives and families, with huge financial burdens for society.
      Although the recent introduction of cooling represents a significant advance,
      only 40% survive with normal neurodevelopmental function. There is thus a
      significant unmet need for novel, safe, and effective therapies to optimize brain
      protection following brain injury around birth. The Na+/H+ exchanger (NHE) is a
      membrane protein present in many mammalian cell types. It is involved in
      regulating intracellular pH and cell volume. NHE1 is the most abundant isoform in
      the central nervous system and plays a role in cerebral damage after hypoxia
      ischemia. Excessive NHE activation during hypoxia-ischemia leads to intracellular
      Na+ overload, which subsequently promotes Ca2+ entry via reversal of the Na+/Ca2+
      exchanger. Increased cytosolic Ca2+ then triggers the neurotoxic cascade.
      Activation of NHE also leads to rapid normalization of pHi and an alkaline shift
      in pHi. This rapid recovery of brain intracellular pH has been termed pH paradox
      as, rather than causing cells to recover, this rapid return to normal and
      overshoot to alkaline values is deleterious to cell survival. Brain pHi changes
      are closely involved in the control of cell death after injury: an alkalosis
      enhances excitability while a mild acidosis has the opposite effect. We have
      observed a brain alkalosis in 78 babies with neonatal encephalopathy serially
      studied using phosphorus-31 magnetic resonance spectroscopy during the first year
      after birth (151 studies throughout the year including 56 studies of 50 infants
      during the first 2 weeks after birth). An alkaline brain pHi was associated with
      severely impaired outcome; the degree of brain alkalosis was related to the
      severity of brain injury on MRI and brain lactate concentration; and a
      persistence of an alkaline brain pHi was associated with cerebral atrophy on MRI.
      Experimental animal models of hypoxia-ischemia show that NHE inhibitors are
      neuroprotective. Here, we review the published data on brain pHi in neonatal
      encephalopathy and the experimental studies of NHE inhibition and neuroprotection
      following hypoxia-ischemia.

PMID- 24452960
TI  - Dual delivery of vascular endothelial growth factor and hepatocyte growth factor
      coacervate displays strong angiogenic effects.
AB  - Controlled delivery of multiple growth factors (GFs) holds great potential for
      the clinical treatment of ischemic diseases and might be more therapeutically
      effective to reestablish vasculature than the provision of a single GF. Vascular
      endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are two
      potent angiogenic factors. However, due to rapid degradation and dilution in the
      body, their clinical potential will rely on an effective mode of delivery. A
      coacervate, composed of heparin and a biodegradable polycation, which protects
      GFs from proteolysis and potentiates their bioactivities, is developed. Here, the
      coacervate incorporates VEGF and HGF and sustains their release for at least
      three weeks. Their strong angiogenic effects on endothelial cell proliferation
      and tube formation in vitro are confirmed. Furthermore, it is demonstrated that
      coacervate-based delivery of these factors has stronger effects than free
      application of both factors and to coacervate delivery of each GF separately. 

PMID- 24452961
TI  - Return of visual function after bilateral visual loss following flow diversion
      embolization of a giant ophthalmic aneurysm due to both reduction in mass effect
      and reduction in aneurysm pulsation.
AB  - Large and giant paraclinoid aneurysms are challenging to treat by either surgical
      or endovascular means. Visual dysfunction secondary to optic nerve compression
      and its relationship with aneurysm size, pulsation and thrombosis is poorly
      understood. We present a patient with a giant paraclinoid aneurysm resulting in
      bilateral visual loss that worsened following placement of a Pipeline
      Embolization Device and adjunctive coiling. Visual worsening occurred in
      conjunction with aneurysm thrombosis, increase in maximal aneurysm diameter and
      new adjacent edema. Her visual function spontaneously improved in a delayed
      fashion to better than pre-procedure, in conjunction with reduced aneurysmal mass
      effect, size and pulsation artifact on MRI. This report documents detailed
      ophthalmologic and MRI evidence for the role of thrombosis, aneurysm mass effect
      and aneurysm pulsation as causative etiologies for both cranial nerve dysfunction
      and delayed resolution following flow diversion treatment of large cerebral
      aneurysms. 

PMID- 24452962
TI  - Bone marrow mesenchymal stromal cells to treat tissue damage in allogeneic stem
      cell transplant recipients: correlation of biological markers with clinical
      responses.
AB  - Bone marrow mesenchymal stromal cells (BMSCs) have been used to treat acute graft
      versus-host disease (GVHD) and other complications following allogeneic
      hematopoietic stem cell transplantation (SCT). We conducted a phase I trial using
      third party, early passage BMSCs for patients with steroid-refractory GVHD,
      tissue injury, or marrow failure following SCT to investigate safety and
      efficacy. To identify mechanisms of BMSC immunomodulation and tissue repair,
      patients were serially monitored for plasma GVHD biomarkers, cytokines, and
      lymphocyte phenotype. Ten subjects were infused a fixed dose of 2 * 10(6)
      BMSCs/kg intravenously weekly for three doses. There was no treatment-related
      toxicity (primary endpoint). Eight subjects were evaluable for response at 4
      weeks after the last infusion. Five of the seven patients with steroid-refractory
      acute GVHD achieved a complete response, two of two patients with tissue injury
      (pneumomediastinum/pneumothorax) achieved resolution but there was no response in
      two subjects with delayed marrow failure. Rapid reductions in inflammatory
      cytokines were observed. Clinical responses correlated with a fall in biomarkers
      (Reg 3alpha, CK18, and Elafin) relevant for the site of GVHD or tissue injury.
      The GVHD complete responders survived significantly longer and had higher
      baseline absolute lymphocyte and central memory CD4 and CD8 counts. Cytokine
      changes also segregated with survival. These results confirm that BMSCs are
      associated with rapid clinical and biomarker responses in GVHD and tissue injury.
      However, BMSCs were ineffective in patients with prolonged GVHD with lower
      lymphocyte counts, which suggest that effective GVHD control by BMSCs requires a
      relatively intact immune system.

PMID- 24452963
TI  - Using photovoice to explore patient perceptions of patient-centered care in the
      Veterans Affairs Health Care System.
AB  - BACKGROUND: Accounting for patient views and context is essential in evaluating
      and improving patient-centered care initiatives, yet few studies have examined
      the patient perspective. In the Veterans Affairs (VA) Health Care System, several
      VA facilities have transitioned from traditionally disease- or problem-based care
      to patient-centered care. We used photovoice to explore perceptions and
      experiences related to patient-centered care among Veterans receiving care in VA
      facilities that have implemented patient-centered care initiatives. DESIGN:
      Participants were provided prompts to facilitate their photography, and were
      asked to capture salient features in their environment that may describe their
      experiences and perceptions related to patient-centered care. Follow-up
      interviews were conducted with each participant to learn more about their
      photographs and intended meanings. Participant demographic data were also
      collected. RESULTS: Twenty-two Veteran patients (n = 22) across two VA sites
      participated in the photovoice protocol. Participants defined patient-centered
      care broadly as caring for a person as a whole while accommodating for individual
      needs and concerns. Participant-generated photography and interview data revealed
      various contextual factors influencing patient-centered care perceptions,
      including patient-provider communication and relationships, physical and social
      environments of care, and accessibility of care. CONCLUSIONS: This study
      contributes to the growing knowledge base around patient views and preferences
      regarding their care, care quality, and environments of care. Factors that shaped
      patient-centered care perceptions and the patient experience included
      communication with providers and staff, decor and signage, accessibility and
      transportation, programs and services offered, and informational resources. Our
      findings may be integrated into system redesign innovations and care design
      strategies that embody what is most meaningful to patients.

PMID- 24452964
TI  - Longitudinal Analysis of Academic Burnout in Korean Middle School Students.
AB  - The purpose of the study was to investigate the longitudinal relationships
      between the initial values and slopes of three dimensions of burnout syndrome
      (i.e. emotional exhaustion, cynicism and academic inefficacy). The study utilized
      four-wave longitudinal data from a total of 367 (81.6% response rate) middle
      school students in South Korea. Comprising a 6-month interval survey, the first
      survey was conducted in June 2010, the second in December 2010, the third in June
      2011 and the fourth in December 2011. All participants were 13-year-olds at the
      first and second surveys, and 14-year-olds at the third and fourth surveys. The
      Maslach Burnout Inventory-Student Survey was used for each survey to assess the
      level of academic burnout. The longitudinal data were analysed using latent
      growth modelling. The results of the study indicated that high initial values
      (intercept) for emotional exhaustion were associated with a higher rate of
      increase (slope) in cynicism and academic inefficacy. On the other hand, high
      initial values for cynicism and academic inefficacy were associated with a lower
      rate of increase in the other dimensions. This longitudinal study should promote
      understanding of burned-out students and contribute to the literature by
      informing the design of prevention programmes for academic burnout.

PMID- 24452965
TI  - Alzheimer's disease and disseminated mycoses.
AB  - Alzheimer's disease (AD) is characterized by the presence in the brain of amyloid
      plaques and neurofibrillary tangles that provoke neuronal cell death, vascular
      dysfunction and inflammatory processes. In the present work, we have analyzed the
      existence of fungal infection in AD patients. A number of tests have been carried
      out in blood serum, including the detection of antibodies against several yeast
      species and fungal proteins, and also the presence of fungal (1,3)-beta-glucan.
      Results from this analysis indicate that there is disseminated fungal infection
      in the majority of AD patients tested. Of interest, several AD patients contain
      high levels of fungal polysaccharides in peripheral blood, reflecting that
      disseminated fungal infection occurs in these patients. Together, these results
      suggest the presence of disseminated mycoses in blood serum from AD patients. To
      our knowledge these findings represent the first evidence that fungal infection
      is detectable in blood samples in AD patients. The possibility that this may
      represent a risk factor or may contribute to the etiological cause of AD is
      discussed.

PMID- 24452966
TI  - The microbiologic profile of diabetic foot infections in Turkey: a 20-year
      systematic review: diabetic foot infections in Turkey.
AB  - The causative pathogens in diabetic foot infections differ in studies of European
      compared with Asian populations. The purpose of this study was to determine the
      causative microorganisms and their antibiotic sensitivity patterns in diabetic
      patients with a foot infection in Turkey, a country at the crossroads of these
      two continents. We performed a comprehensive literature search to identify all
      published studies pertaining to DFIs in patients cared for in Turkey. To assess
      changes in causative organisms and their antibiotic sensitivity patterns over
      time, we compared the results of just the most recent 5 years (2007-2011) with
      those of the past 20-years (1989-2011). We identified 31 studies meeting our
      inclusion criteria. Overall, these studies reported 2,097 patients, from whom
      1,974 microorganisms were isolated. The total percentage of gram-negative and
      gram-positive aerobic bacteria were similar in each of the assessed periods. The
      rate of isolation of Staphylococcus aureus during the entire period, compared
      with just the past 5 years, was 23.8% and 19.1%, respectively, while the rate of
      methicillin-resistant S. aureus was 7.8% and 5.7%, respectively. The isolation
      rate of Pseudomonas aeruginosa was 13.7% for the entire period and 14.9% for the
      past 5 years. While linezolid, vancomycin and teicoplanin were the most active
      agents against gram-positive microorganisms, imipenem and cefoperazone-sulbactam
      were the most active against gram-negative microorganisms. This systematic review
      demonstrated few substantial changes in diabetic foot microbiology over the past
      20 years. The data may help develop and update local clinical guidelines
      regarding antibiotic therapy for diabetic foot infections in Turkey. Further
      studies, especially with optimal culture methods, would be useful to validate
      these findings.

PMID- 24452967
TI  - Evaluation of phenotypic detection methods for metallo-beta-lactamases (MBLs) in
      clinical isolates of Pseudomonas aeruginosa.
AB  - Metallo-beta-lactamase (MBL) production in Pseudomonas aeruginosa is a growing
      issue across the globe. Fast and reliable diagnostic tools are needed for
      appropriate implementation of infection control measures. In this study we
      evaluated the performance of three commercial combined disk tests, two EDTA based
      in-house combined disk tests and the Carba NP test in comparison to molecular
      detection of MBL genes on 133 meropenem non-susceptible non-duplicate P.
      aeruginosa clinical isolates. The meropenem/DPA based commercial KPC + MBL
      confirm ID kit (Rosco Diagnostica, Denmark) and the MASTDISCSTM ID carbapenemase
      (Enterobacteriaceae) detection disc set (MAST Diagnostics, UK) showed
      sensitivities of 31.1 % and 28.8 % and specificities of 69.3 % and 79.6 %,
      respectively. The total MBL confirm kit (Rosco Diagnostica, Denmark) contains
      imipenem/DPA and imipenem/EDTA combination disks. Evaluation of the single disk
      combinations revealed 84.4 % sensitivity and 81.8 % specificity for the
      imipenem/DPA assay and 86.7 % sensitivity and 51.1 % specificity for the
      imipenem/EDTA test. Applying both tests simultaneously resulted in a slightly
      higher sensitivity of 88.9 % but a lower specificity of 48.9 % when compared to
      the single tests alone. The Carba NP test showed 93.3 % sensitivity and 96.6 %
      specificity. All phenotypic combined disk tests lacked either sensitivity or
      specificity for the detection of MBL in P. aeruginosa. The Carba NP test showed
      excellent test properties, but suffers from drawbacks in handling and high costs.
      The optimal diagnostic approach needs to be chosen depending on the
      epidemiological situation, laboratory resources and availability of molecular
      confirmation tests.

PMID- 24452968
TI  - 25th anniversary article: label-free electrical biodetection using carbon
      nanostructures.
AB  - Nanostructures are promising candidates for use as active materials for the
      detection of chemical and biological species, mainly due to the high surface-to
      volume ratio and the unique physical properties arising at the nanoscale. Among
      the various nanostructures, materials comprised of sp(2) -carbon enjoy a unique
      position due to the possibility to readily prepare them in various dimensions
      ranging from 0D, through 1D to 2D. This review focuses on the use of 1D (carbon
      nanotubes) and 2D (graphene) carbon nanostructures for the detection of
      biologically relevant molecules. A key advantage is the possibility to perform
      the sensing operation without the use of any labels or complex reaction schemes.
      Along this spirit, various strategies reported for the label-free electrical
      detection of biomolecules using carbon nanostructures are discussed. With their
      promise for ultimate sensitivity and the capability to attain high selectivity
      through controlled chemical functionalization, carbon-based nanobiosensors are
      expected to open avenues to novel diagnostic tools as well as to obtain new
      fundamental insight into biomolecular interactions down to the single molecule
      level. 

PMID- 24452970
TI  - Otto Loewi (1873-1961): Dreamer and Nobel laureate.

PMID- 24452971
TI  - Lipoma arborescens.
AB  - Lipoma arborescens is a chronic, slowly progressive intra-articular lesion
      characterised by villous lipomatous proliferation of the synovium, usually
      involving the suprapatellar pouch of the knee joint. It is an uncommon cause of
      intra-articular masses that presents as slowly progressive painless swelling of
      the joint, which persists for many years and is accompanied by intermittent
      effusions. We highlight this condition to raise awareness of its clinical
      spectrum and imaging features, so that early diagnosis and appropriate treatment
      can be given, and misinterpretation of this condition as other more complex intra
      articular masses is avoided. This pictorial essay aims to provide a brief yet
      comprehensive review of the clinical features, distribution, morphological types
      and imaging characteristics of lipoma arborescens, including its common
      differential diagnoses and management. 

PMID- 24452972
TI  - Childhood immunisation.
AB  - Primary care practitioners play an important role in administering and advocating
      childhood vaccination to protect our children against infectious diseases and to
      ensure herd immunity in our population. Primary care practitioners may encounter
      children who present out-of-schedule, as well as children who come for
      vaccination with intercurrent illnesses, egg or other allergies, or are on long
      term medications. This article describes the approach to these issues and present
      useful resources and references that primary care practitioners can access. 

PMID- 24452973
TI  - An audit of preoperative fasting compliance at a major tertiary referral hospital
      in Singapore.
AB  - INTRODUCTION: To avoid the risk of pulmonary aspiration, fasting before
      anaesthesia is important. We postulated that the rate of noncompliance with
      fasting would be high in patients who were admitted on the day of surgery.
      Therefore, we surveyed patients in our institution to determine the rate of
      fasting compliance. We also examined patients' knowledge on preoperative fasting,
      as well as their perception of and attitudes toward preoperative fasting.
      METHODS: Patients scheduled for 'day surgery' or 'same day admission surgery'
      under general or regional anaesthesia were surveyed over a four-week period. The
      patients were asked to answer an eighteen-point questionnaire on demographics,
      preoperative fasting and attitudes toward fasting. RESULTS: A total of 130
      patients were surveyed. 128 patients fasted before surgery, 111 patients knew
      that they needed to fast for at least six hours before surgery, and 121 patients
      believed that preoperative fasting was important, with 103 believing that
      preoperative fasting was necessary to avoid perioperative complications. However,
      patient understanding was poor, with only 44.6% of patients knowing the reason
      for fasting, and 10.8% of patients thinking that preoperative fasting did not
      include abstinence from beverages and sweets. When patients who did and did not
      know the reason for fasting were compared, we did not find any significant
      differences in age, gender or educational status. CONCLUSION: Despite the
      patients' poor understanding of the reason for fasting, they were highly
      compliant with preoperative fasting. This is likely a result of their perception
      that fasting was important. However, poor understanding of the reason for fasting
      may lead to unintentional noncompliance.

PMID- 24452974
TI  - A bibliometric study of scientific research conducted on second-generation
      antipsychotic drugs in Singapore.
AB  - INTRODUCTION: A bibliometric study was carried out to ascertain the volume and
      impact of scientific literature published on second-generation antipsychotic
      drugs (SGAs) in Singapore from 1997 to 2011. METHODS: A search of the EMBASE and
      MEDLINE databases was performed to identify articles originating from Singapore
      that included the descriptors 'atypic* antipsychotic*', 'second-generation
      antipsychotic*', 'clozapine', 'risperidone', 'olanzapine', 'ziprasidone',
      'quetiapine', 'sertindole', 'aripiprazole', 'paliperidone', 'amisulpride',
      'zotepine', 'asenapine', 'iloperidone', 'lurasidone', 'perospirone' and
      'blonanserin' in the article titles. Certain bibliometric indicators of
      production and dispersion (e.g. Price's Law on the increase of scientific
      literature, and Bradford's Law) were applied, and the participation index of
      various countries was calculated. The bibliometric data was also correlated with
      some social and health data from Singapore, such as the total per capita
      expenditure on health and gross domestic expenditure on research and development.
      RESULTS: From 1997 to 2011, a total of 51 articles on SGAs in Singapore were
      published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after
      exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely
      studied drugs were clozapine (21 articles), risperidone (16 articles) and
      olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied
      by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore
      Medical Journal(4 articles). The analysed material was published in a total of 30
      journals, with the majority from six journals. Four of these six journals have an
      impact factor greater than 2. CONCLUSION: Publications on SGAs in Singapore are
      still too few to confirm an exponential growth of scientific literature.

PMID- 24452976
TI  - Multiple variations of the tendons of the anatomical snuffbox.
AB  - INTRODUCTION: Multiple tendons of the abductor pollicis longus (APL) in the
      anatomical snuffbox of the wrist can lead to the development of de Quervain's
      syndrome, which is caused by stenosing tenosynovitis. A cadaveric study was
      performed to establish the variations present in the tendons of the anatomical
      snuffbox in a Malaysian population, in the hope that this knowledge would aid
      clinical investigation and surgical treatment of de Quervain's tenosynovitis.
      METHODS: Routine dissection of ten upper limbs was performed to determine the
      variations in the tendons of the anatomical snuffbox of the wrist. RESULTS: In
      all the dissected upper limbs, the APL tendon of the first extensor compartment
      was found to have several (3-14) tendon slips. The insertion of the APL tendon
      slips in all upper limbs were at the base of the first metacarpal bone, trapezium
      and fascia of the opponens pollicis muscle; however, in seven specimens, they
      were also found to be attached to the fleshy belly of the abductor pollicis
      brevis muscle. In two specimens, double tendons of the extensor pollicis longus
      located in the third extensor compartment were inserted into the capsule of the
      proximal interphalangeal joints before being joined to the extensor expansion. In
      two other specimens, the first extensor compartment had two osseofibrous tunnels
      divided by a septum that separated the APL tendon from the extensor pollicis
      brevis tendon. CONCLUSION: Multiple variations were found in the anatomical
      snuffbox region of the dissected upper limbs. Knowledge of these variations would
      be useful in interventional radiology and orthopaedic surgery.

PMID- 24452975
TI  - Reactivity of allergy skin test in healthy volunteers.
AB  - INTRODUCTION: Healthy individuals may be exposed and sensitised to allergens, and
      have a positive response to a skin prick test despite being asymptomatic. The
      objectives of this study were to evaluate the prevalence of atopic sensitisation
      and identify the reactivity of healthy volunteers to common aeroallergens.
      METHODS: Healthy volunteers with no known allergic symptoms were recruited in
      this study. All volunteers were scheduled to undergo a skin prick test with 16
      common aeroallergens that were previously identified among atopic patients.
      RESULTS: A total of 100 volunteers (mean age 28 years) were enrolled in this
      study. 42 volunteers had positive skin prick tests for at least one allergen. The
      median number of sensitised allergen was 2 (range 1-7). Volunteers with positive
      skin tests (n = 42) were younger than those with negative skin tests (n = 58)
      (mean age 25.5 vs. 29.2 years; p < 0.05). The group with positive skin tests also
      had a higher proportion of males (57.1% vs. 31.0%; p < 0.01) and first-degree
      relatives with a history of atopic diseases (31.0% vs. 10.3%; p < 0.05). The most
      common sensitised allergens in these healthy asymptomatic volunteers were mite (n
      = 33), house dust (n = 23) and American cockroach (n = 20). CONCLUSION: In this
      study, up to 42% of healthy volunteers, particularly those with a family history
      of atopy, were sensitised to allergens. Reactivity of the skin test without
      allergic symptoms, however, does not indicate allergic disease. Therefore, the
      skin test should only be indicated in atopic symptomatic individuals.

PMID- 24452977
TI  - Anatomical study of the suprascapular notch: quantitative analysis and clinical
      considerations for suprascapular nerve entrapment.
AB  - INTRODUCTION: Detailed anatomical knowledge of the suprascapular notch (SSN) is
      important for the management of entrapment neuropathy and interventional
      procedures. The objective of the present study was to collect data on the
      morphological features and anatomical variations of the SSN in an Indian
      population. METHODS: We studied 268 human scapulae of unknown sex (126 right
      sided, 142 left-sided) taken from the Department of Anatomy, Dayanand Medical
      College and Hospital, India. SSNs were classified as either type I, II, III, IV
      or V, based on the shape of the inferior border of the incisura, and comparison
      of the SSN's vertical and transverse diameters. The shape of the SSN (i.e V- or U
      shaped), if present, was also recorded. RESULTS: Type II SSN was the most common
      (50.00%), followed by type I, type IV and type III (32.46%, 9.70% and 7.84%,
      respectively). For right-sided type II SSNs, the transverse and vertical
      diameters were 9.1 +/- 3.2 mm and 5.2 +/- 1.9 mm, respectively, while those for
      left-sided type ll SSNs were 9.2 +/- 2.4 mm and 5.1 +/- 1.8 mm, respectively.
      Generally, the transverse diameter of type II SSN was found to be greater than
      that of type III SSN. The incidence of U-shaped SSN was 51.49%, while that of V
      shaped SSN was 2.99%. CONCLUSION: This study of the morphometrical
      characteristics and anatomical variations of SSN provides an anatomical database
      of SSN in the Indian context. This database will be of use in surgical
      procedures, as the information can be used to ensure adequate access to and
      complete decompression of the suprascapular nerve.

PMID- 24452978
TI  - The forensic significance of enteric duplication.

PMID- 24452981
TI  - Exogenous ochronosis in a Chinese patient: use of dermoscopy aids early diagnosis
      and selection of biopsy site.
AB  - The diagnosis of exogenous ochronosis is often challenging and requires a high
      index of suspicion. Herein, we report a case of exogenous ochronosis in a Chinese
      patient. The condition was caused by the use of bleaching agents, including
      creams containing hydroquinone. We demonstrate the use of dermoscopy as an
      invaluable tool for the early recognition of the condition, as well as in the
      selection of an appropriate site for a skin biopsy. 

PMID- 24452982
TI  - Cystic lymphoid hyperplasia of the parotid gland as the initial manifestation of
      HIV infection.
AB  - We report the case of a patient who presented with cystic lymphoid hyperplasia of
      the right parotid gland as the index diagnosis of HIV infection. Histological
      examination of the excised parotid gland revealed a solid-cystic lymphoepithelial
      lesion with a non-keratinous squamous epithelium, which grew into the lymphoid
      component via anastomosing cords and islands. These anastomosing cords and
      islands contained variably abundant B cells, several subepithelial multinucleated
      histiocytes, salivary ducts infiltrated by small lymphocytes, and a dense
      lymphoid infiltrate containing lymphoid follicles with enlarged, irregular
      germinal centres. 

PMID- 24452983
TI  - Isoniazid-induced cerebellitis: a disguised presentation.
AB  - Cerebellitis is a rarely encountered complication of isoniazid therapy. Its
      occurrence is usually associated with concomitant renal disease and
      haemodialysis. Herein, we report the case of a patient with this complication who
      presented with isolated bilateral symmetrical dentate nucleus T2 hyperintensities
      on magnetic resonance imaging. Isoniazid neurotoxicity has never been reported to
      cause bilateral dentate hyperintensities, for which the differentials are few and
      include metronidazole toxicity. 

PMID- 24452984
TI  - Recurrent and persistent pityriasis rosea: an atypical case presentation.
AB  - We report a case of atypical pityriasis rosea in a 24-year-old Malay man. He
      presented with an 11-month history of three recurrent and persistent episodes of
      pityriasis rosea associated with oral ulcers. The first episode lasted for one
      month and recurred within 14 days. The second episode lasted for three months and
      recurred within nine days. The third episode lasted for seven months. Although
      all three episodes were not preceded by any prodromal symptoms, a herald patch
      was noted on three different sites (the left iliac fossa, abdomen and chest) on
      each successive episode. Recurrent pityriasis rosea and its association with oral
      ulcers, although quite uncommon, have been reported in the literature. However,
      reports of multiple recurrences, with prolonged duration of each episode and very
      short remissions in between, have not been made. To the best of our knowledge,
      this is the first report of such unique presentation. 

PMID- 24452985
TI  - Melanonychia and mucocutaneous hyperpigmentation from hydroxyurea use for the
      treatment of essential thrombocytosis.
AB  - Hydroxyurea is an antineoplastic agent commonly used to treat essential
      thrombocytosis. We report the case of a 50-year-old woman who was incidentally
      detected to have essential thrombocytosis after suffering an episode of
      cerebrovascular accident with faciobrachial monoparesis. She was subsequently
      initiated on hydroxyurea. Within seven weeks of therapy, the patient noticed
      irregular hyperpigmented patches over her feet, hands and perioral region, with
      bluish-grey longitudinal bands on all 20 nails. Hydroxyurea-induced
      hyperpigmentation and melanonychia are not commonly reported. To the best of our
      knowledge, this is only the third published report of hydroxyurea-induced
      hyperpigmentation and melanonychia involving all 20 nails. Physicians need to be
      aware of such mucocutaneous side effects to avoid misdiagnosis and unwarranted
      fear in patients. The decision to discontinue the intake of the drug depends
      heavily on the future risk of thrombotic events. 

PMID- 24452986
TI  - Anaesthetic management of a premature low-birth-weight neonate with congenital
      complete heart block for implantation of temporary epicardial pacing wires.
AB  - The optimal anaesthetic management of neonates with complete congenital heart
      block (CCHB) is unknown, as there is a low incidence of such cases. Neonates with
      CCHB often require surgery for the initiation of electronic pacing. In addition
      to the challenges of anaesthetising a neonate, this procedure is risky due to the
      potential for hypotension, arrhythmias and cardiac arrest. We herein present the
      case of a premature low-birth-weight neonate with antibody-related CCHB and
      normal heart structure who underwent anaesthesia and surgery for epicardial
      pacing wire insertion on Day 1 of life. We also compare our patient's anaesthetic
      conduct and outcome with similar previously reported cases. 

PMID- 24452987
TI  - High resolution non-invasive detection of a fetal microdeletion using the GCREM
      algorithm.
AB  - BACKGROUND/OBJECTIVE: The non-invasive prenatal detection of fetal microdeletions
      becomes increasingly challenging as the size of the mutation decreases, with
      current practical lower limits in the range of a few megabases. Our goals were to
      explore the lower limits of microdeletion size detection via non-invasive
      prenatal tests using Minimally Invasive Karyotyping (MINK) and introduce/evaluate
      a novel statistical approach we recently developed called the GC Content Random
      Effect Model (GCREM). METHODS: Maternal plasma was obtained from a pregnancy
      affected by a 4.2-Mb fetal microdeletion and three normal controls. Plasma DNA
      was subjected to capture an 8-Mb sequence spanning the breakpoint region and
      sequence. Data were analyzed with our published method, MINK, and a new method
      called GCREM. RESULTS: The 8-Mb capture segment was divided into either 38 or 76
      non-overlapping regions of 200 and 100 Kb, respectively. At 200 Kb resolution,
      using GCREM (but not MINK), we obtained significant adjusted p-values for all 20
      regions overlapping the deleted sequence, and non-significant p-values for all 18
      reference regions. At 100 Kb resolution, GCREM identified significant adjusted p
      values for all but one 100-Kb region located inside the deleted region.
      CONCLUSION: Targeted sequencing and GCREM analysis may enable cost effective
      detection of fetal microdeletions and microduplications at high resolution.

PMID- 24452990
TI  - Prevention and early treatment of peritoneal metastases from colorectal cancer:
      second-look laparotomy or prophylactic HIPEC?

PMID- 24452989
TI  - Ensemble MD simulations restrained via crystallographic data: accurate structure
      leads to accurate dynamics.
AB  - Currently, the best existing molecular dynamics (MD) force fields cannot
      accurately reproduce the global free-energy minimum which realizes the
      experimental protein structure. As a result, long MD trajectories tend to drift
      away from the starting coordinates (e.g., crystallographic structures). To
      address this problem, we have devised a new simulation strategy aimed at protein
      crystals. An MD simulation of protein crystal is essentially an ensemble
      simulation involving multiple protein molecules in a crystal unit cell (or a
      block of unit cells). To ensure that average protein coordinates remain correct
      during the simulation, we introduced crystallography-based restraints into the MD
      protocol. Because these restraints are aimed at the ensemble-average structure,
      they have only minimal impact on conformational dynamics of the individual
      protein molecules. So long as the average structure remains reasonable, the
      proteins move in a native-like fashion as dictated by the original force field.
      To validate this approach, we have used the data from solid-state NMR
      spectroscopy, which is the orthogonal experimental technique uniquely sensitive
      to protein local dynamics. The new method has been tested on the well-established
      model protein, ubiquitin. The ensemble-restrained MD simulations produced lower
      crystallographic R factors than conventional simulations; they also led to more
      accurate predictions for crystallographic temperature factors, solid-state
      chemical shifts, and backbone order parameters. The predictions for (15) N R1
      relaxation rates are at least as accurate as those obtained from conventional
      simulations. Taken together, these results suggest that the presented
      trajectories may be among the most realistic protein MD simulations ever
      reported. In this context, the ensemble restraints based on high-resolution
      crystallographic data can be viewed as protein-specific empirical corrections to
      the standard force fields. 

PMID- 24452991
TI  - Nutmeg poisonings: a retrospective review of 10 years experience from the
      Illinois Poison Center, 2001-2011.
AB  - Nutmeg is a commonly consumed spice. The toxic effects of nutmeg have been
      purported to be due mainly to myristicin oil. Prior poison center series of
      nutmeg exposures show very few unintentional exposures of nutmeg to children
      younger than 13. Case series from these centers did not record drug exposures
      combined with nutmeg. This study is a review of Illinois Poison Center (IPC) data
      regarding nutmeg exposures from January of 2001 to December 2011. The goal of
      this study was to compare the Illinois data to the literature as well as look for
      current trends in nutmeg poisonings. The data were extracted using the code for
      hallucinogenic plants in the IPC database, and poisonings unrelated to nutmeg
      exposure were eliminated. Medical outcomes were noted as recorded. Thirty-two
      cases of nutmeg ingestion were reported. Of the 17 (53.1 %) unintentional
      exposures, 10 subjects (58.8 %) were under the age of 13. Four of the exposures
      in children under the age of 13 were ocular exposures. Fifteen exposures (46.9 %)
      were intentional exposures. Of these intentional exposures, five (33.3 %) were
      recorded to have combined drug intoxication. All of these were between the ages
      of 15 and 20. One patient with polypharmaceutical exposure required ventilatory
      support in the hospital. Our study shows an unexpected percentage of
      unintentional exposures in juveniles under the age of 13, out of the total
      exposures to nutmeg. Mixing of nutmeg with other drugs was seen and required more
      intervention in adolescents. More education about these two factors, i.e., nutmeg
      exposures as intentional polypharmacy in adolescents and unintentional exposures
      in young children, is advised. 

PMID- 24452992
TI  - Using discrete trial training to identify specific learning impairments in boys
      with fragile X syndrome.
AB  - We examined whether discrete trial training (DTT) could be used to identify
      learning impairments in mathematical reasoning in boys with fragile X syndrome
      (FXS). Boys with FXS, aged 10-23 years, and age and IQ-matched controls, were
      trained to match fractions to pie-charts and pie-charts to decimals either on a
      computer or with a trained behavior analyst using DTT. Participants with FXS
      obtained significantly lower learning rates on the fractions to pie-charts task,
      and were more likely to perseverate on previously reinforced responses during
      learning compared to controls. These data suggest that DTT can be used to
      identify specific learning impairments in boys with FXS, as well as other low
      functioning individuals with developmental disabilities.

PMID- 24452993
TI  - A general catalytic hydroamidation of 1,3-dienes: atom-efficient synthesis of N
      allyl heterocycles, amides, and sulfonamides.
AB  - Transition-metal-catalyzed hydroamination reactions are sustainable and atom
      economical C?N bond-forming processes. Although remarkable progress has been made
      in the inter- and intramolecular amination of olefins and 1,3-dienes, related
      intermolecular reactions of amides are still much less known. Control of the
      regioselectivity without analogous telomerization is the particular challenge in
      the catalytic hydroamidation of alkenes and 1,3-dienes. Herein, we report a
      general protocol for the hydroamidation of electron-deficient N-heterocyclic
      amides and sulfonamides with 1,3-dienes and vinyl pyridines in the presence of a
      catalyst derived from [{Pd(pi-cinnamyl)Cl}2 ] and ligand L7 or L10. The reactions
      proceeded in good to excellent yield with high regioselectivity. The practical
      utility of our method is demonstrated by the hydroamidation of functionalized
      biologically active substrates. The high regioselectivity for linear amide
      products makes the procedure useful for the synthesis of a variety of allylic
      amides. 

PMID- 24452994
TI  - Insight into the structures of the second and fifth transmembrane domains of
      Slc11a1 in membrane mimics.
AB  - Slc11a1 is an integral membrane protein with 12 putative transmembrane domains
      and functions as a pH-coupled divalent metal cation transporter. In the present
      study, the structures of the peptides corresponding to the second and fifth
      transmembrane domains of Slc11a1 (from 88 to 109 for TMD2 and from 190 to 215 for
      TMD5) were determined in membrane-mimic environments by CD and NMR techniques. It
      was demonstrated that TMD2 and TMD5 form an alpha-helical structure in 30% 2,2,2
      trifluoroethanol (TFE) and 40% hexafluoro-2-propanol (HFIP) aqueous solution,
      respectively. The alpha-helix of TMD5 displays a less space-occupied face
      consisting of the residues Ala194, Gly197, Thr201, Ala204 and Gly208. The alpha
      helix is partially unfolded in the N-terminal region when Gly197 is substituted
      by Val. The unfolding of the helix in the N-terminal part and/or increase in
      volume at the less space-occupied face of the helix may exert an effect on the
      arrangement of TMD5 in membrane.

PMID- 24452995
TI  - Phase II trial of adjuvant oral thalidomide following cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy for peritoneal surface disease from
      colorectal/appendiceal cancer.
AB  - PURPOSE: This phase II single-institution trial of adjuvant thalidomide after
      cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      for patients with appendiceal and colorectal malignancies sought to detect an
      improvement in progression-free survival (PFS) from 7 to 12 months. METHODS:
      Eligible patients received CS, HIPEC, and baseline imaging, followed by
      pretreatment thalidomide counseling. All participants were then started on a 28
      day regimen of thalidomide, 100 mg by mouth at bedtime, followed by 200 mg for 4
      weeks, followed by 300 mg as the final maintenance dose, as tolerated. RESULTS:
      Twenty-seven eligible patients (median age 52 years; 52% appendiceal/48%
      colorectal) were enrolled on this trial and included in the analysis, and 26 were
      evaluable for response. Eighteen patients demonstrated stable disease on adjuvant
      thalidomide, while eight showed evidence of progression. Approximately 30% of the
      patients withdrew due to toxicity. Grade 3/4 toxicities included neurological
      disorders (16%), nausea (12%), vomiting (8%), and thromboembolism (8%). Median
      overall survival (OS) and PFS were 43.0 and 9.3 months, respectively, and median
      follow-up was 40.4 months. Multivariate modeling showed significant improvements
      in PFS and OS for appendiceal patients and those with R0 or R1 resections. On an
      intent-to-treat analysis, the PFS of the study group was 9 months. CONCLUSIONS:
      Based on these findings, thalidomide cannot be recommended as adjuvant therapy
      after CS and HIPEC for gastrointestinal malignancies. Further research is needed
      to identify active agents in this population.

PMID- 24452996
TI  - Listeria monocytogenes can form biofilms in tap water and enter into the viable
      but non-cultivable state.
AB  - Listeria monocytogenes is a foodborne pathogen that can be transmitted through
      contaminated raw food or by ready-to-eat products that have been in contact with
      contaminated surfaces. Tap water (TW) is used to wash produce, as a processed
      food constituent and to wash processing surfaces and floors. The main aim of this
      work was to investigate the formation and survival of L. monocytogenes biofilms
      on stainless steel (SS) coupons in TW at 4, 22, 30 and 37  degrees C. For that,
      coupons with biofilm were visualised in situ while other coupons were scraped to
      quantify total cells by SYTO 9, cultivable numbers by plating onto brain heart
      infusion agar and viable numbers by the direct viable count method. Results
      showed that L. monocytogenes can form biofilms on SS surfaces in TW at any
      temperature, including at 4  degrees C. The number of total cells was similar for
      all the conditions tested while cultivable numbers varied between the level of
      detection (<8.3 CFU cm(-2)) and 3.5 * 10(5) CFU cm(-2), meaning between 7.0 *
      10(4) and 1.1 * 10(7) cells cm(-2) have entered the viable but non-cultivable
      (VBNC) state. This work clearly demonstrates that L. monocytogenes can form
      biofilms in TW and that sessile cells can remain viable and cultivable in some
      conditions for at least the 48 h investigated. On the other hand, VBNC adaptation
      suggests that the pathogen can remain undetectable using traditional culture
      recovery techniques, which may give a false indication of processing surface
      hygiene status, leading to potential cross-contamination of food products.

PMID- 24452997
TI  - Antidepressant drugs and the risk of suicide in children and adolescents.
AB  - Government agencies have issued warnings about the use of antidepressant
      medications in children, adolescents, and young adults since 2003. The statements
      warn that such medications may cause de novo 'suicidality' in some people. This
      review explores the data on the treatment of depression that led to these
      warnings and subsequent data that are relevant to the warnings. It also addresses
      the effectiveness of antidepressant treatment in general and the relationship of
      suicide rates to antidepressant treatment. It concludes that the decisions for
      the 'black box' warnings were based on biased data and invalid assumptions.
      Furthermore, the decisions were unsupported by the observational data regarding
      suicide in young people that existed in 2003. The following recommendations would
      seem to follow from these observations. First, drug authorities should re
      evaluate the basis for their imposed warnings on antidepressant medicines, and
      analyze the actual public health consequences the warnings have had. In the
      absence of substantial evidence supporting the warnings, they should be removed.
      Second, physicians and other providers with prescription privileges should
      continue to be educated regarding the importance of aggressively treating
      depression in young people, using antidepressants when indicated. Third,
      physicians and other professionals who treat depressed young people must always
      be aware of the risk of suicide (albeit quite low) and observe them closely for
      any signs of increased risk of suicide. This is necessary regardless of the type
      of treatment being provided. 

PMID- 24452998
TI  - Interventions for Mooren's ulcer.
AB  - BACKGROUND: Mooren's ulcer is a chronic, painful peripheral ulcer of the cornea.
      Its cause is unknown but it can or will lead to loss of vision if untreated.
      Severe pain is common in patients with Mooren's ulcer and the eye(s) may be
      intensely reddened, inflamed and photophobic, with tearing. The disease is rare
      in the northern hemisphere but more common in southern and central Africa, China
      and the Indian subcontinent. There are a number of treatments used such as anti
      inflammatory drugs (steroidal and non-steroidal), cytotoxic drugs (topical and
      systemic), conjunctivectomy and cornea debridement (superficial keratectomy).
      There is no evidence to show which is the most effective amongst these treatment
      modalities. OBJECTIVES: The aim of this systematic review is to assess the
      effectiveness of the various interventions (medical and surgical) for Mooren's
      ulcer. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and
      Vision Group Trials Register) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE,
      Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid
      OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1980 to June 2013), Latin
      American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to
      June 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled
      trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 4 June 2013. SELECTION CRITERIA: We planned to include randomised controlled
      trials (RCTs) or discuss any prospective non-RCTs in the absence of any RCTs. The
      trials included would be of people of any age or gender diagnosed with Mooren's
      ulcer and all interventions (medical and surgical) would be considered. DATA
      COLLECTION AND ANALYSIS: Two authors screened the search results independently;
      we found no studies that met our inclusion criteria. MAIN RESULTS: As we found no
      studies that met our inclusion criteria, we highlighted important considerations
      for conducting RCTs in the future in this area. AUTHORS' CONCLUSIONS: We found no
      evidence in the form of RCTs to assess the treatment effect for the various
      interventions for Mooren's ulcer. High quality RCTs that compare medical or
      surgical interventions across different demographics are needed. Such studies
      should make use of various outcome measures, (i.e. healed versus not healed,
      percentage of area healed, speed of healing etc.) as well as ensuring high
      quality randomisation and data analysis, as highlighted in this review .

PMID- 24452999
TI  - Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment.
AB  - Mesenchymal stem cells (MSC) are present in most, if not all, tissues and are
      believed to contribute to tissue regeneration and the tissue immune
      microenvironment. Murine MSCs exert immunosuppressive effects through production
      of inducible nitric oxide synthase (iNOS), whereas human MSCs use indoleamine 2,3
      dioxygenase (IDO). Thus, studies of MSC-mediated immunomodulation in mice may not
      be informative in the setting of human disease, although this critical difference
      has been mainly ignored. To address this issue, we established a novel humanized
      system to model human MSCs, using murine iNOS(-/-) MSCs that constitutively or
      inducibly express an ectopic human IDO gene. In this system, inducible IDO
      expression is driven by a mouse iNOS promoter that can be activated by
      inflammatory cytokine stimulation in a similar fashion as the human IDO promoter.
      These IDO-expressing humanized MSCs (MSC-IDO) were capable of suppressing T
      lymphocyte proliferation in vitro. In melanoma and lymphoma tumor models, MSC-IDO
      promoted tumor growth in vivo, an effect that was reversed by the IDO inhibitor 1
      methyl-tryptophan. We found that MSC-IDO dramatically reduced both tumor
      infiltrating CD8(+) T cells and B cells. Our findings offer an important new line
      of evidence that interventional targeting of IDO activity could be used to
      restore tumor immunity in humans, by relieving IDO-mediated immune suppression of
      MSCs in the tumor microenvironment as well as in tumor cells themselves.

PMID- 24453000
TI  - Activated ERBB2/HER2 licenses sensitivity to apoptosis upon endoplasmic reticulum
      stress through a PERK-dependent pathway.
AB  - HER2/Neu/ERBB2 is a receptor tyrosine kinase overexpressed in approximately 20%
      of human breast tumors. Truncated or mutant isoforms that show increased
      oncogenicity compared with the wild-type receptor are found in many breast
      tumors. Here, we report that constitutively active ERBB2 sensitizes human breast
      epithelial cells to agents that induce endoplasmic reticulum stress, altering the
      unfolded protein response (UPR) of these cells. Deregulation of the ERK, AKT, and
      mTOR activities elicited by mutant ERBB2 was involved in mediating this
      differential UPR response, elevating the response to endoplasmic reticulum
      stress, and apoptotic cell death. Mechanistic investigations revealed that the
      increased sensitivity of mutant ERBB2-expressing cells to endoplasmic reticulum
      stress relied upon a UPR effector signaling involving the PERK-ATF4-CHOP pathway,
      upregulation of the proapoptotic cell surface receptor TRAIL-R2, and activation
      of proapoptotic caspase-8. Collectively, our results offer a rationale for the
      therapeutic exploration of treatments inducing endoplasmic reticulum stress
      against mutant ERBB2-expressing breast tumor cells.

PMID- 24453001
TI  - Chromosome 10, frequently lost in human melanoma, encodes multiple tumor
      suppressive functions.
AB  - Although many DNA aberrations in melanoma have been well characterized, including
      focal amplification and deletions of oncogenes and tumor suppressors, broad
      regions of chromosomal gain and loss are less well understood. One possibility is
      that these broad events are a consequence of collateral damage from targeting
      single loci. Another possibility is that the loss of large regions permits the
      simultaneous repression of multiple tumor suppressors by broadly decreasing the
      resident gene dosage and expression. Here, we test this hypothesis in a targeted
      fashion using RNA interference to suppress multiple candidate residents in broad
      regions of loss. We find that loss of chromosome regions 6q, 10, and 11q21-ter is
      correlated with broadly decreased expression of most resident genes and that
      multiple resident genes impacted by broad regional loss of chromosome 10 are
      tumor suppressors capable of affecting tumor growth and/or invasion. We also
      provide additional functional support for Ablim1 as a novel tumor suppressor. Our
      results support the hypothesis that multiple cancer genes are targeted by
      regional chromosome copy number aberrations.

PMID- 24453003
TI  - Molecular rules governing de novo methylation in cancer.
AB  - De novo methylation of CpG islands is seen in many cancers, but the general rules
      governing this process are not known. By analyzing DNA from tumors, as well as
      normal tissues, and by utilizing a range of published data, we have identified a
      universal set of tumor targets, each with its own "coefficient" of methylation
      that is largely correlated with its inherent relative ability to recruit
      polycomb. This pattern is initially formed by a slow process of de novo
      methylation that occurs during aging and then undergoes expansion early in
      tumorigenesis, where we hypothesize that it may act as an inhibitor of
      development-associated gene activation.

PMID- 24453004
TI  - Cancer-associated mutations in healthy individuals: assessing the risk of
      carcinogenesis.
AB  - Mutations associated with hematopoietic malignancies have been repeatedly
      identified in healthy individuals. For certain cases, such as the t(14;18)
      translocation and monoclonal B-cell lymphocytosis, no clear link between the
      presence of aberrant cells and the later development of cancer has been
      established. Intriguingly, longitudinal studies suggest that these abnormalities
      persist for long periods of time in some individuals, but in others are transient
      in which they disappear completely. Here, we present a mathematical model, based
      on cellular replication limits, that provides a possible explanation for these
      seemingly contradictory findings. It proposes that the transient and persistent
      nature of the phenotypes depends on the stage in the differentiation pathway of a
      given lineage in which the mutation originates. Our work suggests that cellular
      replication limits may not only prevent cancer by aborting clonal expansion of
      cells, but also by influencing the fate of altered but nonneoplastic cells in
      healthy tissue.

PMID- 24453002
TI  - Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate
      therapeutic target in glioblastoma.
AB  - Glioblastoma is the most common and aggressive histologic subtype of brain cancer
      with poor outcomes and limited treatment options. Here, we report the selective
      overexpression of the protein arginine methyltransferase PRMT5 as a novel
      candidate theranostic target in this disease. PRMT5 silences the transcription of
      regulatory genes by catalyzing symmetric dimethylation of arginine residues on
      histone tails. PRMT5 overexpression in patient-derived primary tumors and cell
      lines correlated with cell line growth rate and inversely with overall patient
      survival. Genetic attenuation of PRMT5 led to cell-cycle arrest, apoptosis, and
      loss of cell migratory activity. Cell death was p53-independent but caspase
      dependent and enhanced with temozolomide, a chemotherapeutic agent used as a
      present standard of care. Global gene profiling and chromatin immunoprecipitation
      identified the tumor suppressor ST7 as a key gene silenced by PRMT5. Diminished
      ST7 expression was associated with reduced patient survival. PRMT5 attenuation
      limited PRMT5 recruitment to the ST7 promoter, led to restored expression of ST7
      and cell growth inhibition. Finally, PRMT5 attenuation enhanced glioblastoma cell
      survival in a mouse xenograft model of aggressive glioblastoma. Together, our
      findings defined PRMT5 as a candidate prognostic factor and therapeutic target in
      glioblastoma, offering a preclinical justification for targeting PRMT5-driven
      oncogenic pathways in this deadly disease.

PMID- 24453005
TI  - [(18)F]Fluoropyruvate: radiosynthesis and initial biological evaluation.
AB  - The radiosynthesis of [(18)F]fluoropyruvate was investigated using numerous
      precursors were synthesized from ethyl 2,2-diethoxy-3-hydroxypropanoate (5)
      containing different leaving groups: mesylate, tosylate, triflate, and nonaflate.
      These precursors were evaluated for [(18)F]fluoride incorporation with triflate
      being superior. The subsequent hydrolysis step was investigated, and an acidic
      hydrolysis was optimized. After establishing suitable purification and
      formulation methods, the [(18)F]fluoropyruvate could be isolated in ca. 50% d.c.
      yield. The [(18)F]fluoropyruvate was evaluated in vitro for its uptake into tumor
      cells using adenocarcinomic human alveolar basal epithelial cells (A549) and
      unfortunately showed an uptake of approximately 0.1% of the applied dose per
      100,000 cells after 30 min. Initial pharmacokinetic properties were assessed in
      vivo using nude mice showed a high degree of bone uptake from defluorination,
      which will limit its potential as an imaging agent for metabolic processes.

PMID- 24453006
TI  - Effect of prey richness on a consumer's intrinsic growth rate.
AB  - The intrinsic growth rate of non-selective microbivores increases asymptotically
      with increasing prey biomass, but we do not know how intrinsic growth rate is
      affected by prey richness. The objective of this experiment was to determine the
      effect of prey richness on the growth kinetics of nematode predators while
      grazing on mixed bacterial lawns. We found that the intrinsic growth rate of
      Caenorhabditis elegans in laboratory culture increased asymptotically with prey
      richness. The mechanism of this pattern was primarily due to the best available
      prey species in the mixture: the intrinsic growth rate of the consumer feeding on
      a mixture of prey was approximately equal to the intrinsic growth rate of the
      predator when feeding on the single best prey in monoculture. This was analogous
      to the selection effect observed in biodiversity-ecosystem functioning
      relationships. Generation time, and not reproductive output, was the life history
      trait component that was most consistent with the pattern of intrinsic growth
      rate. Our results suggest that in order to link invertebrate consumers' growth
      rates to their microbial species composition in the field, it will be necessary
      to determine the ability of microbivorous invertebrates to selectively forage in
      natural environments and to better understand the micro-scale distribution of
      microbial communities in their natural environments. 

PMID- 24453007
TI  - Climate change and grazing interact to alter flowering patterns in the Mongolian
      steppe.
AB  - Socio-economic changes threaten nomadic pastoralism across the world, changing
      traditional grazing patterns. Such land-use changes will co-occur with climate
      change, and while both are potentially important determinants of future ecosystem
      functioning, interactions between them remain poorly understood. We investigated
      the effects of grazing by large herbivores and climate manipulation using open
      top chambers (OTCs) on flower number and flowering species richness in mountain
      steppe of northern Mongolia. In this region, sedentary pastoralism is replacing
      nomadic pastoralism, and temperature is predicted to increase. Grazing and OTCs
      interacted to affect forb flowering richness, which was reduced following grazing
      removal, and reduced by OTCs in grazed plots only. This interaction was directly
      linked to the soil moisture and temperature environments created by the
      experimental treatments: most species flowered when both soil moisture and
      temperature levels were high (i.e. in grazed plots without OTCs), while fewer
      species flowered when either temperature, or moisture, or both, were low. Removal
      of grazing increased the average number of graminoid flowers produced at peak
      flowering in Year 1, but otherwise grazing removal and OTCs did not affect
      community-level flower composition. Of four abundant graminoid species examined
      individually, three showed increased flower number with grazing removal, while
      one showed the reverse. Four abundant forb species showed no significant response
      to either treatment. Our results highlight how climate change effects on mountain
      steppe could be contingent on land-use, and that studies designed to understand
      ecosystem response to climate change should incorporate co-occurring drivers of
      change, such as altered grazing regimes. 

PMID- 24453008
TI  - Prenatal diagnosis of chromosomal mosaicism in over 1600 cases using array
      comparative genomic hybridization as a first line test.
AB  - OBJECTIVE: The aim of this study was to assess the detection of chromosomal
      mosaicism in chorionic villus (CVS) and amniotic fluid (AF) samples using array
      comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase
      chain reaction. METHODS: All patients undergoing invasive prenatal testing by
      aCGH at a specialist prenatal screening service were included in the study. A
      total of 1609 samples (953 CVS and 656 AF) underwent quantitative fluorescent
      polymerase chain reaction and targeted aCGH without concurrent conventional G
      banded karyotyping. RESULTS: Chromosomal mosaicism was detected in 20 of the 1609
      cases (1.24%); of which 17 were derived from 953 CVS (1.78%), and three from 656
      AF (0.46%). Mosaicism was observed at a level as low as 9%. Four cases were
      likely confined placental mosaicism, 12 were likely true fetal mosaicism, and
      four cases were unable to be classified into either group. CONCLUSIONS: This
      study demonstrates that the use of aCGH as a first line test is able to identify
      chromosomal mosaicism down to 9%, which is lower than the level reliably detected
      using standard cytogenetic analysis. aCGH avoids the disadvantages of culturing,
      which include culture bias, artifact, and culture failure.

PMID- 24453009
TI  - Flexible fabrication of biomimetic bamboo-like hybrid microfibers.
AB  - Biomimetic and flexible bamboo-like hybrid fibers are produced using a novel one
      step strategy. By combining a droplet microfluidic technique with a wet-spinning
      process, biocompatible microfibers are incorporated with polymer spheres or
      multicellular spheroids. As a result of the controllability of this approach, it
      has potential applications in materials science and tissue engineering. 

PMID- 24453011
TI  - Multilingual education of students on a global scale and perspective
      international networking on the example of bioindication and biomonitoring (B&B
      technologies).
AB  - Living or formerly living organisms are being used to obtain information on the
      quality of the general health status of our environment by bioindication and
      biomonitoring methods for many decades. Thus, different roads toward this common
      scientific goal were developed by a lot of different international research
      groups. Global cooperation in between various scientific teams throughout the
      world has produced common ideas, scientific definitions, and highly innovative
      results of this extremely attractive working field. The transdisciplinary
      approach of different and multifaceted scientific areas-starting from biology,
      analytical chemistry, via health physics, up to social and economic issues-have
      surpassed mental barriers of individual scientists, so that "production" of
      straightforward common results related to the influence of material and
      immaterial environmental factors to the well-being of organisms and human life
      has now reached the forefront of international thinking. For the further
      sustainable development of our common scientific "hobby" of bioindication and
      biomonitoring, highest personal energy has to be given by us, being teachers to
      our students and to convince strategically decision makers as politicians to
      invest (financially) into the development of education and research of this
      innovative technique. Young people have to be intensively convinced on the
      "meaning" of our scientific doing, e.g., by extended forms of education. One
      example of multilingual education of students on a global scale and perspective
      is given here, which we started about 3 years ago. 

PMID- 24453012
TI  - Review on physical and chemical characterizations of contaminated sediments from
      urban stormwater infiltration basins within the framework of the French
      observatory for urban hydrology (SOERE URBIS).
AB  - Urban stormwater infiltration basins are designed to hold runoff from impervious
      surfaces and allow the settling of sediments and associated pollutants. However
      concerns have been expressed about the environmental impacts that may be exerted
      by the trapped pollutants on groundwater, soils and ecosystems. In this context,
      sediment characterization represents a key issue for local authorities in terms
      of management strategies. During the last two decades, several studies were
      launched including either physical or chemical characterization of stormwater
      sediments but without real synthesis of data and methods used. Consequently,
      there is an important need for reviewing the current experimental techniques
      devoted to the physico-chemical characterization of sediment. The review is based
      on the outcomes of two experimental sites for which long term monitoring and data
      collection have been done: the Chevire basin (near Nantes) and the Django
      Reinhardt basin (near Lyon). The authors summarize the studies dealing with bulk
      properties, pollutant contents, their potential mobility and speciation. This
      paper aims at promoting the significant progresses that were made through a
      multidisciplinary approach involving multi-scaled and combined experimental
      techniques. 

PMID- 24453013
TI  - Saline irrigation and Zn amendment effect on Cd phytoavailability to Swiss chard
      (Beta vulgaris L.) grown on a long-term amended agricultural soil: a human risk
      assessment.
AB  - Crops, particularly in the Northeast region of Mexico, have to cope with
      increasing soil salinization due to irrigation. Chloride (Cl(-)) concentration
      has been strongly related to enhance cadmium (Cd) uptake by plants due to
      increased solubility in the soil solution. The effect of irrigation with slightly
      saline water from a local well was evaluated in this work on the accumulation and
      translocation of Cd in Swiss chard (Beta vulgaris L.) grown in soil historically
      amended with stabilized sewage sludge under a regime of phosphorus and zinc
      fertilization. A factorial pot experiment was conducted with two phosphate
      fertilizer levels (PF, 0 and 80 kg ha(-1) dry soil, respectively), two Zn levels
      (0 and 7 kg ha(-1) dry soil), and two sources of water for irrigation deionized
      water (DW) and slightly saline well water (WW) from an agricultural site.
      Additionally, a human risk assessment for Cd ingestion from plants was assessed.
      Results showed that Cl(-) salinity in the WW effectively mobilized soil Cd and
      increased its phytoavailability. A higher level of Cd was found in roots (46.41
      mg kg(-1)) compared to shoots (10.75 mg kg(-1)). Although the total content of Cd
      in the edible parts of the Swiss chard irrigated with WW exceeded permissible
      recommended consumption limit, bioavailable cadmium in the aboveground parts of
      the plant in relation to the total cadmium content was in the range from 8 to 32
      %. Therefore, human health risks might be overestimated when the total
      concentration is taken into account. 

PMID- 24453014
TI  - Sonochemical degradation of diclofenac: byproduct assessment, reaction mechanisms
      and environmental considerations.
AB  - The study covers a thorough assessment of the overall degradation of diclofenac
      Na (DCF) by high-frequency ultrasound, focusing particularly on identification,
      interpretation, and characterization of the oxidation byproducts and their
      reaction mechanisms. It was found that sonication of 5 mg L(-1) DCF at near
      neutral pH rendered complete conversion of the compound, 45 % carbon, 30 %
      chlorine, and 25 % nitrogen mineralization. Density functional theory (DFT)
      calculations confirmed the experimentally detected major byproduct 2,6
      dichloroaniline, the formation of which was explained by OH* addition to the ipso
      position of the amino group. The stability of UV absorption at around 276-280 nm
      throughout reaction was in agreement with the detected byproduct structures,
      i.e., the presence of amino/amine groups and phenolic, aniline, benzene, and
      quinine-type derivatives, which all absorbed at around the same band. Microtox
      toxicity of the reactor aliquots at early reaction showed that initially the
      reaction products, specifically 1-(2,6-dichlorophenyl)-2-indoline-one, were very
      toxic; subsequently toxicity exhibited a fluctuating pattern, and a steady
      declination towards the "non-toxic" level was observed only after 90 min. Oxygen
      uptake analysis also revealed the formation of harmful products at early
      reaction, but the reactor was totally biodegradable upon 1-h sonication. 

PMID- 24453015
TI  - Continuous flow photo-Fenton treatment of ciprofloxacin in aqueous solutions
      using homogeneous and magnetically recoverable catalysts.
AB  - The degradation of ciprofloxacin was studied in aqueous solutions by using a
      continuous flow homogeneous photo-Fenton process under simulated solar light. The
      effect of different operating conditions on the degradation of ciprofloxacin was
      investigated by changing the hydrogen peroxide (0-2.50 mM) and iron(II) sulphate
      (0-10 mg Fe L(-1)) concentrations, as well as the pH (2.8-10), irradiance (0-750
      W m(-2)) and residence time (0.13-3.4 min) of the process. As expected, the
      highest catalytic activity in steady state conditions was achieved at acidic pH
      (2.8), namely 85 % of ciprofloxacin conversion, when maintaining the other
      variables constant (i.e. 2.0 mg L(-1) of iron(II), 2.50 mM of hydrogen peroxide,
      1.8 min of residence time and 500 W m(-2) of irradiance). Additionally, magnetite
      magnetic nanoparticles (ca. 20 nm of average particle size) were synthesized,
      characterized and tested as a possible catalyst for this reaction. In this case,
      the highest catalytic activity was achieved at natural pH, namely a 55 % average
      conversion of ciprofloxacin in 1.8 min of residence time and under 500 W m(-2).
      Some of the photocatalytic activity was attributed to Fe(2+) leaching from the
      magnetic nanoparticles to the solution.

PMID- 24453016
TI  - Outbreak of fatal nitrate toxicosis associated with consumption of fennels
      (Foeniculum vulgare) in cattle farmed in Campania region (southern Italy).
AB  - Nitrate and nitrite are toxicants that have become increasingly significant
      environmental chemicals. Increase in environmental distribution of nitrogenous
      compounds, especially in surface and ground water, has been attributed to the
      intensive use of nitrate as agricultural fertilizers and to increasing amounts of
      nitrogenous wastes produced by municipalities, industries, and feedlots. The
      purpose of this study is to illustrate a fatal nitrate toxicosis in cattle
      associated with the consumption of fennels (Foeniculum vulgare). Fifteen cows
      from the same farm suddenly developed weakness, muscular tremors, respiratory
      distress, and finally convulsions. The affected animals died within 24 to 48 h
      from the onset of the clinical signs. Five cows underwent a complete post-mortem
      examination. In all examined animals, gross lesions included presence of dark
      unclotted blood around the nostrils and the anal region, moderate inflammation of
      the gastrointestinal mucosa, and brown discoloration of the skeletal muscles and
      kidneys. The histological examination showed tubular degeneration and congestion
      of glomerular vessels in the kidney. Toxicological analysis detected nitrates at
      4 672.2 ppm in the fennels used to feed the animals. The source of exposure to
      nitrates was identified in the fennels. The fennels were grown in a polluted area
      of the Campania region in southern Italy and distributed in a public market for
      human consumption. The waste from the sale of the fennels was fed to the cows.
      The accumulation of nitrates in some vegetables poses a risk not only for animal
      health but also for human and environmental safety. 

PMID- 24453017
TI  - Does energy consumption contribute to environmental pollutants? Evidence from
      SAARC countries.
AB  - The objective of the study is to examine the causal relationship between energy
      consumption and environmental pollutants in selected South Asian Association for
      Regional Cooperation (SAARC) countries, namely, Bangladesh, India, Nepal,
      Pakistan, and Srilanka, over the period of 1975-2011. The results indicate that
      energy consumption acts as an important driver to increase environmental
      pollutants in SAARC countries. Granger causality runs from energy consumption to
      environmental pollutants, but not vice versa, except carbon dioxide (CO2)
      emissions in Nepal where there exists a bidirectional causality between CO2 and
      energy consumption. Methane emissions in Bangladesh, Pakistan, and Srilanka and
      extreme temperature in India and Srilanka do not Granger cause energy consumption
      via both routes, which holds neutrality hypothesis. Variance decomposition
      analysis shows that among all the environmental indicators, CO2 in Bangladesh and
      Nepal exerts the largest contribution to changes in electric power consumption.
      Average precipitation in India, methane emissions in Pakistan, and extreme
      temperature in Srilanka exert the largest contribution. 

PMID- 24453018
TI  - Temperature and nutrients are significant drivers of seasonal shift in
      phytoplankton community from a drinking water reservoir, subtropical China.
AB  - Reservoirs are an important source of water supply in many densely populated
      areas in southeast China. Phytoplankton plays an important role in maintaining
      the structure and function of these reservoir ecosystems. Understanding of
      seasonal succession in phytoplankton communities and its driving factors is
      essential for effective water quality management in drinking-water reservoirs. In
      this study, water samples were collected monthly at the surface layers of
      riverine, transitional, and lacustrine zones from May 2010 to April 2011 in
      Tingxi Reservoir, southeast China. The phytoplankton showed distinct seasonal
      shifts in community structure at both taxonomic and functional levels. Cyanophyta
      was the dominant group in summer, especially species of Raphidiopsis in May and
      Aphanizomenon in June, and cyanobacterial dominance was promoted by both warmer
      conditions and excessive nutrients loading. Cyanophyta was gradually replaced by
      Cryptophyta (e.g., Chroomonas caudata) in abundance and by Bacillariophyta
      (Fragilaria sp. or Synedra sp. and Melosira sp.) in biomass with decreasing
      temperature. It appeared that seasonal shifts in phytoplankton composition were
      closely related to climate, nutrient status, and hydrology in this reservoir. Our
      partial RDA results clearly showed that water temperature and nutrients (TN and
      TP) were the most critical factors driving phytoplankton community shift in the
      abundance and biomass data, respectively. Further, with the global warming,
      cyanobacterial blooms may increase in distribution, duration, and intensity. In
      our study, the abundance and biomass of cyanobacteria had significant and
      positive correlations with temperature and phosphorus. Therefore, a stricter
      limit on nutrient input should be a priority in watershed management to protect
      drinking water from the effects of cyanobacterial blooms, especially in high
      temperature period. 

PMID- 24453019
TI  - Elevated CO2 concentration increase the mobility of Cd and Zn in the rhizosphere
      of hyperaccumulator Sedum alfredii.
AB  - The effects of elevated CO2 on metal species and mobility in the rhizosphere of
      hyperaccumulator are not well understood. We report an experiment designed to
      compare the effects of elevated CO2 on Cd/Zn speciation and mobility in the
      rhizosphere of hyperaccumulating ecotype (HE) and a non-hyperaccumulating ecotype
      (NHE) of Sedum alfredii grown under ambient (350 MUl l(-1)) or elevated (800 MUl
      l(-1)) CO2 conditions. No difference in solution pH of NHE was observed between
      ambient and elevated CO2 treatments. For HE, however, elevated CO2 reduced soil
      solution pH by 0.22 unit, as compared to ambient CO2 conditions. Elevated CO2
      increased dissolved organic carbon (DOC) and organic acid levels in soil solution
      of both ecotypes, but the increase in HE solution was much greater than in NHE
      solution. After the growth of HE, the concentrations of Cd and Zn in soil
      solution decreased significantly regardless of CO2 level. The visual MINTEQ
      speciation model predicted that Cd/Zn-DOM complexes were the dominant species in
      soil solutions, followed by free Cd(2+) and Zn(2+) species for both ecotypes.
      However, Cd/Zn-DOM complexes fraction in soil solution of HE was increased by the
      elevated CO2 treatment (by 8.01 % for Cd and 8.47 % for Zn, respectively). Resin
      equilibration experiment results indicated that DOM derived from the rhizosphere
      of HE under elevated CO2 (HE-DOM-E) (90 % for Cd and 73 % for Zn, respectively)
      showed greater ability to form complexes with Cd and Zn than those under ambient
      CO2 (HE-DOM-A) (82 % for Cd and 61 % for Zn, respectively) in the undiluted
      sample. HE-DOM-E showed greater ability to extract Cd and Zn from soil than HE
      DOM-A. It was concluded that elevated CO2 could increase the mobility of Cd and
      Zn due to the enhanced formation of DOM-metal complexes in the rhizosphere of HE
      S. alfredii. 

PMID- 24453020
TI  - How complete are E-codes in commercial plan claims databases?

PMID- 24453021
TI  - Anatomy and clinical significance of the uncinate process and uncovertebral
      joint: A comprehensive review.
AB  - INTRODUCTION: The uncinate process and its associated uncovertebral articulation
      are features unique to the cervical spine. This review examines the morphology of
      these unique structures with particular emphasis on the regional anatomy,
      development and clinical significance. MATERIALS AND METHODS: Five electronic
      databases were utilized in the literature search and additional relevant
      citations were retrieved from the references. A total of 74 citations were
      included for review. RESULTS: This literature review found that the uncinate
      processes and uncovertebral articulations are rudimentary at birth and develop
      and evolve with age. With degeneration they become clinically apparent with
      compression of related structures; most importantly affecting the spinal nerve
      root and vertebral artery. The articulations have also been found to precipitate
      torticollis when edematous and be acutely damaged in severe head and neck
      injuries. The uncinate processes are also important in providing stability and
      guiding the motion of the cervical spine. CONCLUSION: This review is intended to
      re-examine an often overlooked region of the cervical spine as not only an
      interesting anatomical feature but also a clinically relevant one.

PMID- 24453022
TI  - Infantile myofibromatosis as an unusual cause for unilateral atelectasis in an
      infant.

PMID- 24453023
TI  - Insulin for glycaemic control in acute ischaemic stroke.
AB  - BACKGROUND: People with hyperglycaemia concomitant with an acute stroke have
      greater mortality, stroke severity, and functional impairment when compared with
      those with normoglycaemia at stroke presentation. This is an update of a Cochrane
      Review first published in 2011. OBJECTIVES: To determine whether intensively
      monitoring insulin therapy aimed at maintaining serum glucose within a specific
      normal range (4 to 7.5 mmol/L) in the first 24 hours of acute ischaemic stroke
      influences outcome. SEARCH METHODS: We searched the Cochrane Stroke Group Trials
      Register (September 2013), CENTRAL (The Cochrane Library 2013, Issue 8), MEDLINE
      (1950 to September 2013), EMBASE (1980 to September 2013), CINAHL (1982 to
      September 2013), Science Citation Index (1900 to September 2013), and Web of
      Science (ISI Web of Knowledge) (1993 to September 2013). We also searched ongoing
      trials registers and SCOPUS. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing intensively monitored insulin therapy versus usual care in
      adults with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: We obtained a
      total of 1565 titles through the literature search. Two review authors
      independently selected the included articles and extracted the study
      characteristics, study quality, and data to estimate the odds ratio (OR) and 95%
      confidence interval (CI), mean difference (MD) and standardised mean difference
      (SMD) of outcome measures. We resolved disagreements by discussion. MAIN RESULTS:
      We included 11 RCTs involving 1583 participants (791 participants in the
      intervention group and 792 in the control group). We found that there was no
      difference between the treatment and control groups in the outcomes of death or
      dependency (OR 0.99, 95% CI 0.79 to 1.23) or final neurological deficit (SMD 
      0.09, 95% CI -0.19 to 0.01). The rate of symptomatic hypoglycaemia was higher in
      the intervention group (OR 14.6, 95% CI 6.6 to 32.2). In the subgroup analyses of
      diabetes mellitus (DM) versus non-DM, we found no difference for the outcomes of
      death and disability or neurological deficit. The number needed to treat was not
      significant for the outcomes of death and final neurological deficit. The number
      needed to harm was nine for symptomatic hypoglycaemia. AUTHORS' CONCLUSIONS:
      After updating the results of our previous review, we found that the
      administration of intravenous insulin with the objective of maintaining serum
      glucose within a specific range in the first hours of acute ischaemic stroke does
      not provide benefit in terms of functional outcome, death, or improvement in
      final neurological deficit and significantly increased the number of
      hypoglycaemic episodes. Specifically, those people whose glucose levels were
      maintained within a tighter range with intravenous insulin experienced a greater
      risk of symptomatic and asymptomatic hypoglycaemia than those people in the
      control group.

PMID- 24453024
TI  - Role of endoplasmic reticulum stress via the PERK signaling pathway in brain
      injury from status epilepticus.
AB  - Endoplasmic reticulum (ER) stress may play a role in status epilepticus (SE).
      Sprague-Dawley rats were randomized into three groups: control (saline), SE
      (pentylenetetrazol), and dentate gyrus (DG), pretreated with 2-deoxy-D-glucose (2
      DG). Expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer
      binding protein homologous protein (CHOP), eukaryotic initiation factor 2alpha
      (eIF2alpha), and protein kinase RNA-like ER kinase (PERK) were determined. CHOP
      messenger RNA (mRNA) and protein expression levels in SE group were significantly
      increased as compared to the control group (P < 0.0001), and significantly
      decreased in DG group as compared to the SE group (P < 0.0001). Phosphorylated
      eIF-2alpha protein expression level in SE group was significantly increased as
      compared to the control group (P < 0.0001) and significantly decreased in DG
      group as compared to the SE group (P < 0.0001). GRP messenger RNA expression
      levels and protein levels in SE group was significantly increased as compared to
      the control group (P < 0.0001) and significantly decreased in DG group as
      compared to the SE group (P < 0.0001). Phosphorylated PERK protein expression
      level in SE group was significantly increased as compared to the control group (P
      < 0.0001), and significantly decreased in DG group as compared to the SE group (P
      < 0.0001) at the time of 12 and 24 h. Our results suggest that brain injury from
      SE might involve ER stress via the pro-apoptotic PERK-eIF2alpha-CHOP signaling
      pathway.

PMID- 24453025
TI  - Outcome of long-axis percutaneous sacroplasty for the treatment of sacral
      insufficiency fractures with a radiofrequency-induced, high-viscosity bone
      cement.
AB  - Our goal was to assess the technical results in patients who underwent long-axis
      sacroplasty for the treatment of sacral insufficiency fractures (SIF) by
      radiofrequency-induced high-viscosity bone cement augmentation. Twelve patients
      with bilateral sacral fractures were treated by augmentation with radiofrequency
      activated, high-viscosity polymethylmethacrylate (PMMA) bone cement under local
      anesthesia. CT-guided sacroplasty was performed by using a long-axis approach
      through a single entry point. Thirty-six vertebrae were treated in 12 sessions
      under a combination of CT and fluoroscopic guidance using a bilateral access and
      a cavity-creating osteotome prior to remote-controlled, hydraulically driven
      cement injection. The visual analogue scale (VAS) score before sacroplasty and at
      1 and 3 months after the treatment was obtained. PMMA leaks were evaluated
      retrospectively using the post-interventional CT. The mean amount of high
      viscosity PMMA injected per patient was 7.8 ml. No major adverse events were
      observed. In the first 4 days after the procedure, the mean VAS score decreased
      from 8.1 +/- 1.9 to mean 3.1 +/- 1.2 and was followed by a gradual but continuous
      decrease throughout the rest of the follow-up period at 24 weeks (mean 2.2 +/-
      1.1) and 48 weeks (mean 2.1 +/- 1.4). CT fluoroscopy-guided sacral augmentation
      was safe and effective in all 12 patients with osteoporotic SIF.

PMID- 24453027
TI  - MDCT findings after elbow dislocation: a retrospective study of 140 patients.
AB  - OBJECTIVE: To assess the number and anatomical location of fractures associated
      with elbow dislocation, to study the correlation between the direction of
      dislocation and the trauma energy, and to assess radiographs' diagnostic
      performance characteristics for fractures using MDCT as a reference standard.
      MATERIALS AND METHODS: A retrospective study was performed at a level 1 trauma
      center, finding a total of 140 patients who had sustained an elbow dislocation
      and who had undergone a subsequent MDCT examination. The CT and radiographs of
      the patient were reviewed by two musculoskeletal radiologists. CT images were
      analyzed for the site and size of the fracture fragments. In addition, the
      primary direction of the dislocation, patients' age, and gender were recorded.
      Trauma energy was also assessed. RESULTS: One hundred and thirty-four out of 140
      patients (96%) had a fracture that was seen on the correlative CT examination.
      The most common anatomical fracture locations were the coronoid process of the
      ulna 84 out of 140 (60%), the radial head 75 out of 140 (54%), and the humeral
      capitellum 57 out of 140 (41%). Multiple fractures were seen in 71 out of 134
      (53%) patients with fractures. The left elbow was more commonly dislocated than
      the right one. The overall sensitivity of the radiographs was 62% and the
      specificity 96%. CONCLUSION: Small fractures and impaction fractures are almost
      invariably present in elbow dislocations, and half of the patients have more than
      one fracture. Radiographs have a sensitivity of only 62%. MDCT is an invaluable
      method for determining the extent of bony injury and revealing occult fractures.

PMID- 24453026
TI  - Magnetic resonance imaging of pelvic entheses--a systematic comparison between
      short tau inversion recovery (STIR) and T1-weighted, contrast-enhanced, fat
      saturated sequences.
AB  - OBJECTIVE: To assess the contribution of contrast material in detecting and
      evaluating enthesitis of pelvic entheses by MRI. MATERIALS AND METHODS: Sixty
      seven hip or pelvic 1.5-T MRIs (30:37 male:female, mean age: 53 years) were
      retrospectively evaluated for the presence of hamstring and gluteus medius (GM)
      enthesitis by two readers (a resident and an experienced radiologist). Short tau
      inversion recovery (STIR) and T1-weighted pre- and post-contrast (T1+Gd) images
      were evaluated by each reader at two sessions. A consensus reading of two senior
      radiologists was regarded as the gold standard. Clinical data was retrieved from
      patients' referral form and medical files. Cohen's kappa was used for intra- and
      inter-observer agreement calculation. Diagnostic properties were calculated
      against the gold standard reading. RESULTS: A total of 228 entheses were
      evaluated. Gold standard analysis diagnosed 83 (36%) enthesitis lesions. Intra
      reader reliability for the experienced reader was significantly (p = 0.0001)
      higher in the T1+Gd images compared to the STIR images (hamstring: k = 0.84/0.45,
      GM: k = 0.84/0.47). Sensitivity and specificity increased from 0.74/0.8 to
      0.87/0.9 in the STIR images and T1+Gd sequences. Intra-reader reliability for the
      inexperienced reader was lower (p > 0.05). CONCLUSIONS: Evidence showing that
      contrast material improves the reliability, sensitivity, and specificity of
      detecting enthesitis supports its use in this setting.

PMID- 24453028
TI  - Bursal synovial chondromatosis formation following osteochondroma resection.
AB  - Osteochondroma is a common tumor of the bone and can be complicated by
      adventitial bursa formation and malignant transformation of the cartilaginous
      cap. Synovial chondromatosis formation within these bursae is extremely rare and
      can be confused with malignant transformation of the osteochondroma cap to a
      chondrosarcoma. We describe a case of extra-articular synovial chondromatosis
      formation several years following osteochondroma resection. Cartilage nodule
      formation within the bursal synovial lining and proliferation of cartilage debris
      shed from the cartilaginous cap during surgery or biopsy are potential etiologies
      of this rare complication of osteochondromas. 

PMID- 24453029
TI  - Association between a functional insertion/deletion polymorphism in IL1A gene and
      risk of papillary thyroid carcinoma.
AB  - The aim of this study was to evaluate whether an insertion/deletion polymorphism
      (rs3783553) locating in the miR-122 target gene IL1A 3' untranslated region was
      related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was
      extracted from peripheral venous blood of 273 patients with PTC and 509 controls.
      The IL1A rs3783553 polymorphism was genotyped by using a polymerase chain
      reaction assay. No significant difference of the distribution of the IL1A
      rs3783553 polymorphism was observed between PTC patients and controls. However,
      patients carrying the IL1A rs3783553 ins/ins genotype and ins allele had
      significantly decreased risks for developing T3 and T4 when compared with
      patients carrying the IL1A rs3783553 del/del genotype and del allele (ins/ins vs.
      del/del: OR = 0.22, 95% confidence interval (CI), 0.09-0.54; ins vs. del: OR =
      0.58, 95% CI, 0.41-0.83, respectively). These results suggest that the rs3783553
      polymorphism may be used as a genetic marker to predict the size/extension of
      PTC.

PMID- 24453030
TI  - DNA repair gene ERCC1 polymorphisms may contribute to the risk of glioma.
AB  - Polymorphisms in excision repair cross-complementing rodent repair deficiency
      complementation group 1 (ERCC1) gene have been shown to affect individual
      susceptibility to glioma, though studies have yielded conflicting results. This
      meta-analysis aims to derive a more precise estimation of the association between
      ERCC1 C8092A and C118T polymorphisms and glioma risk. A literature search of
      PubMed, Embase, Web of Science, Cochrane Library, and CBM databases was conducted
      to identify all eligible studies published before August 5, 2013. Crude odds
      ratios (ORs) with their corresponding confidence intervals (95% CIs) were used to
      assess the strength of this association. A meta-analysis was performed by
      reviewing seven studies on the C8092A polymorphism (2,978 cases and 4,051
      controls) and four studies on the C118T polymorphism (1,390 Asian cases and 1,546
      Asian controls). Pooled analysis yielded a significant association between the
      C8092A variant genotype and increased risk of glioma. As for ethnicity, the A
      allele was associated with increased risk of glioma in Asians, while no similar
      finding was observed in Caucasians. Stratified analyses by histological subtype
      indicated that the C8092A polymorphism showed a significant association with the
      risk of non-glioblastoma multiforme. For the C118T polymorphism, increased glioma
      susceptibility was also observed among Asians. Taken together, results from our
      meta-analysis support the view that common variants in ERCC1 may contribute to
      susceptibility to glioma, especially in Asians. However, further studies
      investigating the significance of these two polymorphisms as markers of
      susceptibility to and disease progression of glioma are still needed.

PMID- 24453031
TI  - The CYP1B1 Leu432Val polymorphism and risk of urinary system cancers.
AB  - The cytochrome P450 1B1 (CYP1B1) gene plays a key role in the metabolism of
      various carcinogens. The CYP1B1 Leu432Val polymorphism leads to leucine to valine
      substitution at codon 432. A lot of studies have shown that the CYP1B1 Leu432Val
      polymorphism was associated with urinary system cancers, especially prostate
      cancer. However, the results were still inconclusive. In this meta-analysis, by
      searching online databases and references of related reviews, we identified 17
      eligible studies to assess the relationship between CYP1B1 Leu432Val polymorphism
      and urinary system cancers, including 7,783 cancer cases and 7,238 controls. By
      pooling all eligible studies, we found that the CYP1B1 Leu432Val polymorphism was
      not associated with overall urinary system cancers. However, in subgroup
      analyses, we found that the variant 432Val allele significantly increased the
      risk of prostate cancer (Val vs. Leu, odds ratio (OR) = 1.064, 95% confidence
      interval (CI) 0.981-1.154; Pheterogeneity = 0.002), while no association was
      found for bladder cancer (Val vs. Leu, OR = 0.942, 95% CI 0.853-1.041;
      Pheterogeneity = 0.504). No evidence of publication bias was found (Begg's test,
      P = 0.053; Egger's test, P = 0.073). In conclusion, based on 17 eligible studies,
      we found that the CYP1B1 Leu432Val polymorphism was associated with an increased
      risk of prostate cancer, while no association of bladder cancer was observed.

PMID- 24453032
TI  - Expression and clinical significance of BIRC6 in human epithelial ovarian cancer.
AB  - Baculoviral IAP repeat containing 6 (BIRC6), an unusually large member of the IAP
      family, may play an important role in oncogenesis. The aim of this study was to
      assess the value of BIRC6 in predicting tumor recurrence after curative resection
      in epithelial ovarian cancer (EOC) patients. In this study, the differences of
      BIRC6 expression in four paired EOC and normal tissue were performed by Western
      blot, and expression of BIRC6 protein was analyzed in 100 clinicopathologically
      characterized EOC cases from those who underwent curative resection between 2003
      and 2011 by immunohistochemistry. Kaplan-Meier survival estimates and log-rank
      tests were used to assess the prognostic significance. It was found that BIRC6
      expression was higher in the carcinoma tissue than in normal control tissue at
      protein level by Western blot. There was a significant difference of BIRC6
      expression in patients categorized according to tumor differentiation (p =
      0.016). Univariate analyses and multivariate analyses revealed that BIRC6 was an
      independent significant predictor for overall survival and disease-free survival.
      A prognostic significance of BIRC6 was also found by Kaplan-Meier method. The
      expression of BIRC6 in the cytoplasm is associated with EOC differentiation and
      may be a novel predictor for poor prognosis of EOC patients after curative
      resection. 

PMID- 24453033
TI  - Detection of circulating antibodies to linear peptide antigens derived from ANXA1
      and DDX53 in lung cancer.
AB  - The EarlyCDT(r)-Lung test was the first autoantibody-based diagnostic tool for
      lung cancer, which was developed with a panel of recombinant protein antigens. To
      confirm whether the antibody test developed with linear peptide antigens has a
      similar power to that developed with the whole protein molecules, the present
      work was then undertaken to develop an in-house enzyme-linked immunosorbent assay
      with linear peptide antigens derived from annexin A1 (ANXA1) and DEAD box protein
      53 (DDX53), which have been used to develop the EarlyCDT(r)-Lung test. A total of
      272 patients with non-small cell lung cancer (NSCLC) and 227 control subjects
      matched in age and smoking history were recruited. Student's t test showed that
      the levels of circulating IgG to ANXA1-derived peptide antigens were
      significantly higher in patients with NSCLC than control subjects (t = 5.66, P <
      0.0001), in which the increased anti-ANXA1 IgG levels were observed only in
      patients at stages I, II, or III, but not in those at stage IV. However, the
      levels of circulating IgG to DDX53-derived peptide antigens were not
      significantly altered in NSCLC (t = 1.78, P = 0.076). Receiver operating
      characteristic analysis showed that the sensitivity against specificity of >90%
      was 23.7% for ANXA1 IgG assay and 13.8% for DDX53 IgG assay. This work suggests
      that the linear peptide antigen derived from ANXA1 may be suitable for the
      development of diagnostic tool for lung cancer although further screening is
      needed to identify more such peptide antigens derived from tumor-associated
      antigens.

PMID- 24453034
TI  - Association study of SNPs of genes IFNGR1 (rs137854905), GSTT1 (rs71748309), and
      GSTP1 (rs1695) in gastric cancer development in samples of patient in the
      northern and northeastern Brazil.
AB  - Cancer is a multifactorial disease with a high mortality rate in Brazil and
      worldwide. Gastric cancer (GC) is considered the fourth type of malignancy more
      frequent in the population worldwide and the second leading cause of death. This
      work aimed to evaluate single nucleotide polymorphisms (SNPs) of IFNGR1, GSTT1,
      and GSTP1 genes samples in gastric cancer. We analyzed 60 samples of gastric
      cancer, 26 diffuse and 34 intestinal types, totaling 120 alleles for each SNP.
      The results were obtained by PCR and allele-specific PCR. Statistical analyzes
      performed using BioEstat 5.0 software, applying the Fisher's exact test and chi
      square. Only the SNP gene GSTP1 (rs1695) were significantly associated with
      gastric cancer in the samples analyzed (chi(2) = 8.73, P < 0.05). Our results
      suggest that the GSTP1 gene SNP (rs1695) can be considered a risk factor
      associated with gastric carcinogenesis.

PMID- 24453035
TI  - The prodrug platin-A: simultaneous release of cisplatin and aspirin.
AB  - Cancer-associated inflammation induces tumor progression to the metastatic stage,
      thus indicating that a chemo-anti-inflammatory strategy is of interest for the
      management of aggressive cancers. The platinum(IV) prodrug Platin-A was designed
      to release cisplatin and aspirin to ameliorate the nephrotoxicity and ototoxicity
      caused by cisplatin. Platin-A exhibited anticancer and anti-inflammatory
      properties which are better than a combination of cisplatin and aspirin. These
      findings highlight the advantages of combining anti-inflammatory treatment with
      chemotherapy when both the drugs are delivered in the form of a single prodrug. 

PMID- 24453036
TI  - Intra-lesional interleukin-2 therapy for in transit melanoma.
AB  - Intra-lesional interleukin-2 (IL-2) is effective in treating in transit melanoma
      metastases. Results from multiple studies were examined to evaluate the efficacy
      of IL-2 for in transit disease. In the published literature, complete response
      ranged from 0% to 69% per patient, and 41% to 96% per lesion, with excellent
      tolerability. Combining the results of six studies show complete response in 50%
      of patients and 78% of lesions. Intra-lesional IL-2 should be considered early in
      the course of treatment for in transit disease, ahead of other, more toxic
      therapies.

PMID- 24453037
TI  - Chiral separability of boron cluster species studied by screening approaches
      utilizing polysaccharide-based chiral stationary phases.
AB  - In this study, the screening steps of chiral separation strategies with
      polysaccharide-based chiral stationary phases were applied on boron cluster
      compounds in normal-phase liquid chromatography (NPLC) and polar organic solvents
      chromatography (POSC). Since the screening steps were initially developed to
      analyze organic compounds, their applicability for boron clusters was
      investigated. Overall, the screening steps in NPLC were applicable for the
      separation of zwitterions, while for anions mostly no elution was observed. A
      hypothesis for the latter behavior is precipitation of anions in the nonpolar
      mobile phases. Ten out of 11 compounds could be partially or baseline separated
      on the NPLC screening systems. In POSC, all zwitterions were separated on at
      least one of the screening systems, with an overall lower retention as in NPLC.
      Anions were detected but not separated in the majority of the experiments. Also
      their retention on the chiral stationary phases was very limited. This study
      showed that the chiral discrimination potential of chemically modified
      polysaccharides is meaningful for chiral separations of structurally chiral boron
      cluster species, but needs further systematic research, in which recognition
      mechanisms should be further explored. In addition, some unusual peaks also
      indicated that conditions with a high separation efficiency must first be
      searched for some of the tested systems.

PMID- 24453038
TI  - Interaction of protamine with gram-negative bacteria membranes: possible
      alternative mechanisms of internalization in Escherichia coli, Salmonella
      typhimurium and Pseudomonas aeruginosa.
AB  - This study was concerned with the interaction between the cationic antimicrobial
      peptide, protamine (Ptm) and the cytoplasmic membranes of the gram-negative
      bacteria Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa. The
      objective of the study was to explain the observed paradox of internalization
      without permanent disruption of the cell envelope. We carried out Monte Carlo
      computer simulation of Ptm in an aqueous environment in the presence of ~100 mM
      NaCl and model membranes consisting of either (65:35) or (75:25) PE:PG molar
      ratios. The (75:25) model, representative of the gram-negative cytoplasmic
      membrane, showed that the Ptm center of mass remained at least 7 nm from the
      membrane surface leading to the prediction that Ptm would not internalize via
      disruption of the inner membrane. By using immunoelectron microscopy of Ptm
      treated cells, we showed that Ptm internalization to the cytoplasm took place
      rapidly in the presence or absence of the outer envelope. Ultrastructural
      examination revealed no obvious morphological changes to cells that were treated
      with subinhibitory or bactericidal levels of Ptm. Reconstituted phospholipid
      bilayers were constructed and were unperturbed by Ptm treatment over a wide range
      of concentrations and applied transmembrane voltages. We conclude that in the
      cases of the cell envelopes of E. coli, S. typhimurium and P. aeruginosa, Ptm
      internalized by means independent of the phospholipid bilayer, most likely
      mediated by one or more membrane proteins such as cation-selective barrel-like
      proteins. Work is currently underway to test this hypothesis.

PMID- 24453039
TI  - Ratiometric MRI sensors based on core-shell nanoparticles for quantitative pH
      imaging.
AB  - Ratiometric MRI sensors consist of paramagnetic cores and pH-sensitive polymer
      shells. The core-shell nanostructure enables the coexistence of two incompatible
      NMR relaxation properties in one particle. The sensors show pH sensitivity in
      transverse relaxivity (r2 ), but not in longitudinal relaxivity (r1 ).
      Quantitative pH imaging is achieved by measuring the r2 /r1 value with a clinical
      3 T MRI scanner. 

PMID- 24453040
TI  - The genome sequence of the highly acetic acid-tolerant Zygosaccharomyces bailii
      derived interspecies hybrid strain ISA1307, isolated from a sparkling wine plant.
AB  - In this work, it is described the sequencing and annotation of the genome of the
      yeast strain ISA1307, isolated from a sparkling wine continuous production plant.
      This strain, formerly considered of the Zygosaccharomyces bailii species, has
      been used to study Z. bailii physiology, in particular, its extreme tolerance to
      acetic acid stress at low pH. The analysis of the genome sequence described in
      this work indicates that strain ISA1307 is an interspecies hybrid between Z.
      bailii and a closely related species. The genome sequence of ISA1307 is
      distributed through 154 scaffolds and has a size of around 21.2 Mb, corresponding
      to 96% of the genome size estimated by flow cytometry. Annotation of ISA1307
      genome includes 4385 duplicated genes (~ 90% of the total number of predicted
      genes) and 1155 predicted single-copy genes. The functional categories including
      a higher number of genes are 'Metabolism and generation of energy', 'Protein
      folding, modification and targeting' and 'Biogenesis of cellular components'. The
      knowledge of the genome sequence of the ISA1307 strain is expected to contribute
      to accelerate systems-level understanding of stress resistance mechanisms in Z.
      bailii and to inspire and guide novel biotechnological applications of this yeast
      species/strain in fermentation processes, given its high resilience to acidic
      stress. The availability of the ISA1307 genome sequence also paves the way to a
      better understanding of the genetic mechanisms underlying the generation and
      selection of more robust hybrid yeast strains in the stressful environment of
      wine fermentations.

PMID- 24453042
TI  - Apoptosis regulation at the mitochondrial outer membrane.
AB  - Mitochondria play a critical role in apoptosis, or programmed cell death, by
      releasing apoptogenic factors from the intermembrane space. This process, known
      as mitochondrial outer membrane permeabilization (MOMP), is tightly regulated by
      the Bcl-2 family proteins. Pro-apoptotic Bcl-2 family members, Bax and Bak,
      change their conformation when activated by BH3 domain-only proteins in the
      family and permeabilize the MOM, whereas pro-survival members inhibit
      permeabilization. The precise nature of the apoptotic pore in the MOM is unknown,
      but is probably lipidic. Furthermore, it has been realized that there is another
      layer of MOMP regulation by a protein factor termed the catalyst in the MOM in
      order for Bax/Bak to achieve efficient and complete membrane permeabilization.
      Mitochondrial dynamics do not affect MOMP directly, but seem closely coordinated
      with MOMP for swift protein efflux from mitochondria. This review will present
      current views on the molecular mechanisms and regulation of MOMP and conclude
      with recent developments in clinical applications based on the knowledge gleaned
      from the investigation.

PMID- 24453041
TI  - Genome-wide evolutionary characterization and expression analyses of WRKY family
      genes in Brachypodium distachyon.
AB  - Members of plant WRKY gene family are ancient transcription factors that function
      in plant growth and development and respond to biotic and abiotic stresses. In
      our present study, we have investigated WRKY family genes in Brachypodium
      distachyon, a new model plant of family Poaceae. We identified a total of 86 WRKY
      genes from B. distachyon and explored their chromosomal distribution and
      evolution, domain alignment, promoter cis-elements, and expression profiles.
      Combining the analysis of phylogenetic tree of BdWRKY genes and the result of
      expression profiling, results showed that most of clustered gene pairs had higher
      similarities in the WRKY domain, suggesting that they might be functionally
      redundant. Neighbour-joining analysis of 301 WRKY domains from Oryza sativa,
      Arabidopsis thaliana, and B. distachyon suggested that BdWRKY domains are
      evolutionarily more closely related to O. sativa WRKY domains than those of A.
      thaliana. Moreover, tissue-specific expression profile of BdWRKY genes and their
      responses to phytohormones and several biotic or abiotic stresses were analysed
      by quantitative real-time PCR. The results showed that the expression of BdWRKY
      genes was rapidly regulated by stresses and phytohormones, and there was a strong
      correlation between promoter cis-elements and the phytohormones-induced BdWRKY
      gene expression. 

PMID- 24453043
TI  - Diversity of hepatocellular carcinoma clones bearing hematopoietic malignancies
      related chromosomal translocation.
AB  - Interpatient heterogeneity of hepatocellular carcinoma has been in-depth
      addressed. Intrapatient heterogeneity is less known. Four clones were freshly
      isolated from an Edmondson grade I HCV-associated hepatocellular carcinoma.
      Biochemical approaches, functional assays and cytogenetics were used. Albumin
      inducibility was uncoupled from canonical cytokeratin profiles, suggesting
      pathological combinations of hepatospecific and biliary markers. Poor
      differentiation and TGFbeta's proproliferative effect on all clones were
      observed. TGFbeta, Interferon alpha and doxorubicin sensitivity levels were found
      highly heterogeneous. Progenitor and stem cells markers OV6 and EpCAM were
      mutually exclusively expressed. All clones were CD44+, while none expressed CD90,
      CD133, or CD117. Three clones displayed a liver progenitor OV6+ phenotype, and
      were susceptible to hepatocytic differentiation, among which one fibroblastoid
      clone displayed intrahepatic parenchymal engraftment capability. A fourth clone,
      the less motile, displayed a cancer stem cell EpCAM+ phenotype, was essentially
      beta-catenin negative, and was as expected devoid of hepatocytic differentiation
      capability, yet the most sensitive to doxorubicin treatment. Cytogenetics
      evidenced in all clones a t(12;22)(p11;q11) translocation found in several
      myelodysplastic syndromes. All clones, that probably derive from EpCAM+ tumor
      cells, display aberrant E-cadherin cytosolic localization. Because of their
      diverse pathophysiolocal features, these freshly isolated, low population
      doubling-defined, HCC clones may provide novel opportunities to tackle HCC
      heterogeneity in a single patient background for therapy improvement purposes,
      especially regarding recently developed targeted strategies.

PMID- 24453045
TI  - Requirement of miR-144 in CsA induced proliferation and invasion of human
      trophoblast cells by targeting titin.
AB  - MicroRNAs (miRNAs) are endogenous 19-25 nucleotide noncoding single-stranded RNAs
      that regulate gene expression by blocking the translation or decreasing the
      stability of mRNAs. In this study, with the treatment of CsA (Cyclosporin A), we
      showed that miR144 expression levels were decreased while titin mRNA expression
      levels were increased in human trophoblast (HT) cells, and identified titin as a
      novel direct target of miR-144. Overexpression of miR-144 suppressed titin and
      its downstream signaling molecule such as p-ERK1/2 and MMP2/9 expression, and
      attenuated cell proliferation and invasion. Forced expression of titin can partly
      rescue the inhibitory effect of miR-144 in the cells. Taken together, these
      findings will shed light to the role and mechanism of miR-144 in regulating HT
      cells proliferation and invasion via miR-144/titin axis, and miR-144 may serve as
      a potential therapeutic target in HT in the future.

PMID- 24453044
TI  - Antibodies against potassium channel interacting protein 2 induce necrosis in
      isolated rat cardiomyocytes.
AB  - Auto-antibodies against cardiac proteins have been described in patients with
      dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti
      KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying
      mechanisms are not fully understood. Therefore, we wanted to explore the
      mechanisms responsible for anti-KChIP2-mediated cell death. Rat cardiomyocytes
      were treated with anti-KChIP2 (C-12). KChIP2 RNA and protein expressions, nuclear
      NF-kappaB, mitochondrial membrane potential Deltapsim, caspase-3 and -9
      activities, necrotic and apoptotic cells, total Ca(2+) and K(+) concentrations,
      and the effects on L-type Ca(2+) channels were quantified. Anti-KChIP2 (C-12)
      induced nuclear translocation of NF-kappaB. Anti-KChIP2 (C-12)-treatment for 2 h
      significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12)
      induced nuclear translocation of NF-kappaB after 1 h. After 6 h, Deltapsim and
      caspase-3 and -9 activities were not significantly changed. After 24 h, anti
      KChIP2 (C-12)-treated cells were 75 +/- 3% necrotic, 2 +/- 1% apoptotic, and 13
      +/- 2% viable. Eighty-six +/- 1% of experimental buffer-treated cells were
      viable. Anti-KChIP2 (C-12) induced significant increases in total Ca(2+) (plus 11
      +/- 2%) and K(+) (plus 18 +/- 2%) concentrations after 5 min. Anti-KChIP2 (C-12)
      resulted in an increased Ca(2+) influx through L-type Ca(2+) channels. In
      conclusion, our results suggest that anti-KChIP2 (C-12) enhances cell death of
      rat cardiomyocytes probably due to necrosis.

PMID- 24453046
TI  - Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate
      cancer cell.
AB  - Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), also known as
      tumor metastasis suppressor gene 1 (TMSG1), was firstly cloned by our laboratory
      in 1999. However, its antitumor molecular mechanisms are still unclear.
      LASS2/TMSG-1 could directly interact with the C subunit of Vacuolar H(+) ATPase
      (V-ATPase), which suggested that LASS2/TMSG1 might inhibit the invasion and
      metastasis through regulating the function of V-ATPase. In this study, we
      explored the effect of small hairpin RNA (shRNA) targeting LASS2/TMSG1 on the
      invasion and metastasis of human prostate carcinoma cell line PC-3M-2B4 with low
      metastatic potential and its functional interaction with V-ATPase. Silencing of
      LASS2/TMSG1 gene in PC-3M-2B4 cells increased V-ATPase activity, extracellular
      hydrogen ion concentration and in turn the activation of secreted MMP-2 and MMP
      9, which coincided with enhancing cell proliferation, cell survival, and cell
      invasion in vitro, as well as acceleration of prostate cancer (PCA) growth and
      lymph node metastases in vivo. Thus we concluded that silencing of LASS2/TMSG1
      enhances invasion and metastasis of PCA cell through increase of V-ATPase
      activity. These results establish LASS2/TMSG1 as a promising therapeutic target
      for advanced PCA.

PMID- 24453047
TI  - Identification of FHL2-regulated genes in liver by microarray and bioinformatics
      analysis.
AB  - FHL2 is a LIM domain protein that is able to form various protein complexes and
      regulate gene transcription. Recent findings showed that FHL2 is a potential
      tumor suppressor gene that was down-regulated in hepatocellular carcinoma. In the
      present study, microarray profiling of gene expression was performed to identify
      the genes regulated by FHL2 in mouse livers. The differentially expressed genes
      were further analyzed by bioinformatics tools including DAVID, KEGG, and STRING.
      Our data illustrate that FHL2 affects genes involved in various functions
      including signal transduction, responses to external stimulus, cancer-related
      pathways, cardiovascular function and regulation of actin cytoskeleton. Moreover,
      a network of differentially expressed genes identified in this study and known
      FHL2-interacting proteins was constructed. Then, genes identified by
      bioinformatics tools and most functional relevant to FHL2 were selected for
      further validation. Finally, the differential expression of Ar, Id3, Inhbe,
      Alas1, Bcl6, Ppardelta, Angptl4, and Erbb4 were confirmed by quantitative real
      time PCR. In summary, we have established a database of genes that are
      potentially regulated by FHL2 and these genes should be future targets for the
      elucidation of functional roles of FHL2.

PMID- 24453048
TI  - Genistein induces cytokinesis failure through RhoA delocalization and anaphase
      chromosome bridging.
AB  - Genistein, an isoflavone abundantly present in soybeans, possesses anticancer
      properties and induces growth inhibition including cell cycle arrest and
      apoptosis. Although abnormal cell division, such as defects in chromosome
      segregation and spindle formation, and polyploidization have been described, the
      mechanisms underlying the induction of abnormal cell division are unknown. In
      this study, we examined the effect of genistein on cell division in cells that
      are synchronized in M phase, since genistein treatment delays mitotic entry in
      asynchronous cells. HeLa S3 cells were arrested at the G2 phase and subsequently
      released into the M phase in presence of genistein. Immunofluorescence staining
      showed that genistein treatment delays M phase progression. Time-lapse analysis
      revealed that the delay occurs until anaphase onset. In addition, genistein
      treatment induces cleavage furrow regression, resulting in the generation of
      binucleated cells. Central spindle formation, which is essential for cytokinesis,
      is partially disrupted in genistein-treated cells. Moreover, aberrant chromosome
      segregation, such as a chromosome bridge and lagging chromosome, occurs through
      progression of cytokinesis. RhoA, which plays a role in the assembly and
      constriction of an actomyosin contractile ring, is delocalized from the cortex of
      the ingressing cleavage furrow. These results suggest that genistein treatment
      induces binucleated cell formation through cleavage furrow regression, which is
      accompanied by chromosome bridge formation and RhoA delocalization. Our results
      provide the mechanism that underlies genistein-induced polyploidization, which
      may be involved in genistein-induced growth inhibition.

PMID- 24453049
TI  - Amnioinfusion for meconium-stained liquor in labour.
AB  - BACKGROUND: Amnioinfusion is thought to dilute meconium present in the amniotic
      fluid and so reduce the risk of meconium aspiration. OBJECTIVES: To assess the
      effects of amnioinfusion for meconium-stained liquor on perinatal outcome. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (1 December 2013). SELECTION CRITERIA: Randomised trials comparing
      amnioinfusion with no amnioinfusion for women in labour with moderate or thick
      meconium staining of the amniotic fluid. DATA COLLECTION AND ANALYSIS: Three
      review authors independently assessed eligibility and trial quality, and
      extracted data. MAIN RESULTS: Fourteen studies of variable quality (4435 women)
      are included.Subgroup analysis was performed for studies from settings with
      limited facilities to monitor the baby's condition during labour and intervene
      effectively, and settings with standard peripartum surveillance.Settings with
      standard peripartum surveillance: there was considerable heterogeneity for
      several outcomes. There was no significant reduction in the primary outcomes
      meconium aspiration syndrome, perinatal death or severe morbidity, and maternal
      death or severe morbidity. There was a reduction in caesarean sections (CSs) for
      fetal distress but not overall. Meconium below the vocal cords diagnosed by
      laryngoscopy was reduced, as was neonatal ventilation or neonatal intensive care
      unit admission, but there was no significant reduction in perinatal deaths or
      other morbidity. Planned sensitivity analysis excluding trials with greater risk
      of bias resulted in an absence of benefits for any of the outcomes
      studied.Settings with limited peripartum surveillance: three studies were
      included. In the amnioinfusion group there was a reduction in CS for fetal
      distress and overall; meconium aspiration syndrome (three studies, 1144 women;
      risk ratio (RR) 0.17, 95% confidence interval (CI) 0.05 to 0.52); perinatal
      mortality (three studies, 1151 women; RR 0.24, 95% CI 0.11 to 0.53) and neonatal
      ventilation or neonatal intensive care unit admission. In one of the studies,
      meconium below the vocal cords was reduced and, in the other, neonatal
      encephalopathy was reduced. AUTHORS' CONCLUSIONS: Amnioinfusion is associated
      with substantive improvements in perinatal outcome only in settings where
      facilities for perinatal surveillance are limited. It is not clear whether the
      benefits are due to dilution of meconium or relief of oligohydramnios.In settings
      with standard peripartum surveillance, some non-substantive outcomes were
      improved in the initial analysis, but sensitivity analysis excluding trials with
      greater risk of bias eliminated these differences. Amnioinfusion is either
      ineffective in this setting, or its effects are masked by other strategies to
      optimise neonatal outcome.The trials reviewed are too small to address the
      possibility of rare but serious maternal adverse effects of amnioinfusion.

PMID- 24453050
TI  - Subcortical anatomy of the lateral association fascicles of the brain: A review.
AB  - Precise knowledge of the connectivities of the different white matter bundles is
      of great value for neuroscience research. Our knowledge of subcortical anatomy
      has improved exponentially during recent decades owing to the development of
      magnetic resonance diffusion tensor imaging tractography (DTI). Although DTI
      tractography has led to important progress in understanding white matter anatomy,
      the precise trajectory and cortical connections of the subcortical bundles remain
      poorly determined. The recent literature was extensively reviewed in order to
      analyze the trajectories and cortical terminations of the lateral association
      fibers of the brain.The anatomy of the following tracts is reviewed: superior
      longitudinal fasciculus, middle longitudinal fasciculus, inferior longitudinal
      fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, frontal
      aslant tract, and vertical occipital fasciculus. The functional role of a tract
      can be inferred from its topography within the brain. Knowing the functional
      roles of the cortical areas connected by a certain bundle, it is possible to
      develop new insights into the putative functional properties of such connections.

PMID- 24453051
TI  - Concise synthesis of 3D pi-extended polyphenylene cylinders.
AB  - The synthesis of structurally well-defined, monodisperse carbon nanotube (CNT)
      sidewall segments poses a challenge in materials science. The synthesis of
      polyphenylene cylinders that comprise typical benzene connectivity to resemble
      precursors of [9,9] and [15,15] CNTs is now reported, and the products were
      characterized by X-ray crystallography. To investigate the oxidative
      cyclodehydrogenation of ring-strained molecules as a final step towards a bottom
      up synthesis of CNT sidewall segments, phenylene-extended cyclic p
      hexaphenylbenzene trimers ([3]CHPB) were prepared, and NMR studies revealed a
      strain-induced 1,2-phenyl shift. It was further shown that an increase in ring
      size leads to selectively dehydrogenated macrocycles. Larger homologues are
      envisioned to give smooth condensation reactions toward graphenic sidewalls and
      should be used in the future as seeds for CNT formation. 

PMID- 24453053
TI  - Utilizing pharmacogenetics in psychiatry: the time has come.

PMID- 24453055
TI  - Macroscopic supramolecular assembly of rigid building blocks through a flexible
      spacing coating.
AB  - Macroscopic supramolecular assembly is a promising method for manufacturing
      macroscopic, ordered structures for tissue-engineering scaffolds. A flexible
      spacing coating is shown to overcome undesired surface and size effects and to
      enable assembly of macroscopic cubes with host/guest groups. The assembled pairs
      disassembled upon introduction of competitive guest molecules, thereby
      demonstrating a multivalent assembly mechanism. 

PMID- 24453052
TI  - Differences in UGT1A1, UGT1A7, and UGT1A9 polymorphisms between Uzbek and
      Japanese populations.
AB  - BACKGROUND AND OBJECTIVES: Uridine-diphosphate glucuronosyltransferase 1A (UGT1A)
      is a key enzyme involved in irinotecan metabolism, and polymorphisms in the UGT1A
      gene are associated with irinotecan-induced toxicity. The aim of this study was
      to elucidate the allele frequencies of UGT1A polymorphisms in healthy Uzbek
      volunteers, and to compare them with those of the Japanese population. METHOD: A
      total of 97 healthy volunteers from Uzbekistan were enrolled and blood samples
      were collected from each participant. Genotyping analysis was performed by
      fragment size analysis for UGT1A1*28, direct sequencing for UGT1A7*3 and
      UGT1A9*22, and TaqMan assays for UGT1A1*93, UGT1A1*6, UGT1A1*27, UGT1A1*60, and
      UGT1A7*12. The frequencies of polymorphisms were compared with the Japanese
      population by using the data previously reported from our study group. RESULTS:
      When the Uzbek and Japanese populations were compared, heterozygotes or
      homozygotes for UGT1A1*28, UGT1A1*60, and UGT1A1*93 were significantly more
      frequent in the Uzbek population (P < 0.01). The rate of UGT1A7*12 was not
      significantly different between the two populations, whereas UGT1A1*6 and
      UGT1A9*22 were significantly less frequent in the Uzbek population (P < 0.05).
      UGT1A7*1 were less prevalent in the Uzbek population than in the Japanese
      population (P < 0.01). CONCLUSION: The Uzbek population has different frequencies
      of polymorphisms in UGT1A genes compared with the Japanese population. A
      comprehensive study of the influence of UGT1A1 polymorphisms on the risk of
      irinotecan-induced toxicity is necessary for optimal use of irinotecan treatment.

PMID- 24453056
TI  - Fibromyalgia syndrome: a somatoform disorder?
AB  - BACKGROUND AND OBJECTIVE: Whether fibromyalgia syndrome (FMS) can be classified
      as a somatoform disorder is under debate. DATABASES AND DATA TREATMENT:
      Literature searches on the classification of FMS as a somatoform disorder were
      performed in Medline and in evidence-based guideline databases. RESULTS: A
      somatoform disorder is defined by medically unexplained somatic symptoms that
      persist for at least 6 months and lead to a significant impairment of the ability
      to function in everyday life. The nature and extent of the symptoms or the
      distress and pre-occupation of the patient cannot be explained fully by a general
      medical condition or by the direct effect of a substance, and are not
      attributable to another mental disorder. Emotional and psychosocial conflicts
      play a major role in the onset, severity, exacerbation or maintenance of the
      physical symptoms. There is disagreement in the FMS research community on the
      existence of somatic factors sufficiently explaining FMS symptoms. Psychosocial
      factors play a major role in the onset, exacerbation or maintenance of FMS
      symptoms in the majority of patients. A biopsychosocial model of interacting
      biological and psychosocial factors in the predisposition, onset and maintenance
      of FMS symptoms is more appropriate than the dichotomy between a somatic disease
      and a mental (somatoform) disorder. CONCLUSIONS: The clinical features of FMS and
      persistent somatoform pain disorder or somatization disorder according to the
      International Classification of Diseases (ICD)-10 overlap in individuals with
      chronic widespread pain without specific somatic disease factors. FMS is not
      synonymous with somatoform disorder.

PMID- 24453057
TI  - Analysis of normal and modified nucleosides in urine samples by high-performance
      liquid chromatography with different stationary phases.
AB  - The main aim of the present work was to study the retention behavior and
      quantification of nine nucleosides with the use of octadecyl, alkylamide,
      cholesterol and alkyl-phosphate stationary phases. The influence of organic
      solvent and buffer concentration on the separation of these compounds was under
      investigation. The retention factor had the highest values for the octadecyl and
      cholesterol packing materials. Complete separation of all the studied nucleosides
      was achieved in case of cholesterol stationary phase. The optimized separation
      method was applied for the quantification of nucleosides in the urine samples.
      Calibration plots showed good linearity (R(2) > 0.999) and the limits of
      detection were in a range of 0.3-0.5 ug/mL, while the limits of quantitation were
      >0.9 ug/mL. Accuracy was in the range of 5-11%.

PMID- 24453058
TI  - Epithelial-to-mesenchymal transition predicts prognosis in clinical gastric
      cancer.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is considered to play an
      important role in cancer invasion and metastasis. METHODS: The mRNA levels of an
      epithelial marker (E-cadherin), mesenchymal marker (vimentin), and Zeb-1 were
      measured in 11 gastric cancer cell lines. Functional analysis was performed using
      Zeb-1 knockdown. EMT status of 116 gastric cancer patients was determined by
      calculating the vimentin/E-cadherin mRNA expression ratio in cancerous tissue and
      the correlation between EMT status, clinicopathological factors, prognosis, and
      Zeb-1 were analyzed. RESULTS: Cell lines were classified as epithelial or
      mesenchymal. Zeb-1 expression was significantly correlated with the mesenchymal
      phenotype. Treatment with Zeb-1 siRNA also reduced the capacity to proliferate,
      migrate, and invade. Patients were classified as epithelial or mesenchymal by V/E
      ratio (vimentin/E-cadherin ratio) and as Zeb-1 low or high expression group. The
      mesenchymal group was significantly associated with diffuse type cancer and stage
      IV. On multivariate analysis, the EMT status (mesenchymal group) was an
      independent prognostic factor (P = 0.022). There was a significant correlation
      between the V/E ratio and Zeb-1 expression (r = 0.73). Patients in Zeb-1 high
      group had significantly poorer survival than those in low group (P = 0.0071).
      CONCLUSIONS: EMT is a critical prognostic factor for gastric cancer. Zeb-1 might
      be a promising therapeutic target.

PMID- 24453060
TI  - An assessment of biodegradability of quaternary carbon-containing fragrance
      compounds: comparison of experimental OECD screening test results and in silico
      prediction data.
AB  - An assessment of biodegradability was carried out for fragrance substances
      containing quaternary carbons by using data obtained from Organisation for
      Economic Co-operation and Development (OECD) 301F screening tests for ready
      biodegradation and from Biowin and Catalogic prediction models. Despite an
      expected challenging profile, a relatively high percentage of common-use
      fragrance substances showed significant biodegradation under the stringent
      conditions applied in the OECD 301F test. Among 27 test compounds, 37% met the
      pass level criteria after 28 d, while another 26% indicated partial breakdown
      (>=20% biodegradation). For several compounds for which structural analogs were
      available, the authors found that structures that were rendered less water
      soluble by either the presence of an acetate ester or the absence of oxygen
      tended to degrade to a lesser extent compared to the primary alcohols or
      oxygenated counterparts under the test conditions applied. Difficulties were
      encountered when attempting to correlate experimental with in silico data.
      Whereas the Biowin model combinations currently recommended by regulatory
      agencies did not allow for a reliable discrimination between readily and
      nonbiodegradable compounds, only a comparably small proportion of the chemicals
      studied (30% and 63% depending on the model) fell within the applicability domain
      of Catalogic, a factor that critically reduced its predictive power. According to
      these results, currently neither Biowin nor Catalogic accurately reflects the
      potential for biodegradation of fragrance compounds containing quaternary
      carbons.

PMID- 24453059
TI  - Neuropsychology reports for childhood brain tumor survivors: implementation of
      recommendations at home and school.
AB  - BACKGROUND: As pediatric brain tumor survivors may experience cognitive decline
      post-treatment, a neuropsychology assessment is often conducted. The assessment
      evaluates the child's cognitive functioning and highlights potential challenges.
      Whilst neuropsychology reports provide recommendations for the home and school,
      how this translates in practice is under researched. This study explored parent
      and teacher understanding of neuropsychology reports, implementation rates for
      recommendations and their perceived effectiveness. Barriers to implementation
      were also investigated. PROCEDURE: Twenty-five semi-structured interviews were
      conducted with 17 parents and 8 teachers of childhood brain tumor survivors from
      15 Australian families who had received a neuropsychology report within 2 years
      of the interview. Twenty-four neuropsychology reports encompassing 131
      recommendations were reviewed. The qualitative methodological framework of Miles
      and Huberman [Miles M, Huberman A. Qualitative data analysis: An expanded
      sourcebook. London: Sage; 1994] was used to analyze interview transcripts with
      QSR NVivo 9.0. RESULTS: The majority of parents and teachers had a sound
      understanding of the report. Implementation of recommendations at home and school
      was 47% and 41%, respectively. Recommendations that did not require extra effort
      and organization appeared more likely to be implemented, however, those perceived
      to be more effective or helpful did not necessarily have higher implementation
      rates. Key reported barriers to implementation barrier were patient reluctance,
      and a lack of parents' willingness to adopt the recommendation. CONCLUSIONS:
      Patient understanding and willingness play a significant role in the
      implementation of neuropsychology recommendations. Collaboration and clear
      communication between the patient, teacher, parent, and neuropsychologist is
      vital for effective management.

PMID- 24453061
TI  - Yellow fever vaccine for patients with HIV infection.
AB  - BACKGROUND: Yellow fever (YF) is an acute viral haemorrhagic disease prevalent in
      tropical Africa and Latin America. The World Health Organization (WHO) estimates
      that there are 200,000 cases of YF and 30,000 deaths worldwide annually.
      Treatment for YF is supportive, but a live attenuated virus vaccine is effective
      for preventing infection. WHO recommends immunisation for all individuals > 9
      months living in countries or areas at risk. However, the United States Advisory
      Committee on Immunization Practices (ACIP) advises that YF vaccine is
      contraindicated in individuals with HIV. Given the large populations of HIV
      infected individuals living in tropical areas where YF is endemic, YF vaccine may
      be an important intervention for preventing YF in immunocompromised populations.
      OBJECTIVES: To assess the risk and benefits of YF immunisation for people
      infected with HIV. SEARCH METHODS: We used standard Cochrane methods to search
      electronic databases and conference proceedings with relevant search terms
      without limits to language. SELECTION CRITERIA: Randomised controlled trials and
      cohort studies of individuals with HIV infection who received YF vaccine (17DD or
      17D-204). DATA COLLECTION AND ANALYSIS: Two authors screened abstracts of
      references identified by electronic or bibliographic searches according to
      inclusion and exclusion criteria as detailed in the protocol. We identified 199
      references and examined 19 in detail for study eligibility. Data were abstracted
      independently using a standardised abstraction form. MAIN RESULTS: Three cohort
      studies were included in the review. They examined 484 patients with HIV
      infection who received YF immunisation. Patients with HIV infection developed
      significantly lower concentrations of neutralising antibodies in the first year
      post immunisation compared to uninfected patients, though decay patterns were
      similar for recipients regardless of HIV infection. No study patient with HIV
      infection suffered serious adverse events as a result of YF vaccination. AUTHORS'
      CONCLUSIONS: YF vaccination can produce protective levels of neutralising
      antibodies in HIV patients. Immunogenicity of YF vaccine is slightly less in HIV
      infected patients compared to HIV-uninfected patients. No serious adverse events
      related to YF vaccine were observed in HIV-infected study participants. At time
      of immunisation, higher CD4 cell counts and lower HIV RNA levels in patients with
      HIV infection seem to be key determinants for development of protective titres of
      neutralising antibodies. The quality of the evidence for all outcomes was low to
      very low. YF vaccine may potentially be used safely in HIV-infected patients,
      although our conclusions are limited by small numbers of patients who have been
      reported. To assure maximum effectiveness YF vaccine should be given to HIV
      infected patients after HIV replication has been suppressed.

PMID- 24453062
TI  - Clinical and surgical anatomy of the liver: a review for clinicians.
AB  - The liver is the largest gland in the body occupying 2.5% of total body weight
      and providing a host of functions necessary for maintaining normal physiological
      homeostasis. Despite the complexity of its functions, the liver has a homogenous
      appearance, making hepatic anatomy a challenging topic of discussion. To address
      this issue, scholars have devoted time to establishing a framework for describing
      hepatic anatomy to aid clinicians. Work by the anatomist Sir James Cantlie
      provided the first accurate division between the right and left liver in 1897.
      The French surgeon and anatomist Claude Couinaud provided additional insight by
      introducing the Couinaud segments on the basis of hepatic vasculature. These
      fundamental studies provided a framework for medical and surgical discussions of
      hepatic anatomy and were essential for the advancement of modern medicine. In
      this article, the authors review the normal anatomy and physiology of the liver
      with a view to enhancing the clinician's knowledge base. They also provide a
      convenient model to assist with understanding and discussion of liver anatomy.

PMID- 24453063
TI  - Ruthenium-catalyzed cascade C-H functionalization of phenylacetophenones.
AB  - Three orthogonal cascade C?H functionalization processes are described, based on
      ruthenium-catalyzed C?H alkenylation. 1-Indanones, indeno indenes, and indeno
      furanones were accessed through cascade pathways by using arylacetophenones as
      substrates under conditions of catalytic [{Ru(p-cymene)Cl2 }2 ] and
      stoichiometric Cu(OAc)2 . Each transformation uses C?H functionalization methods
      to form C?C bonds sequentially, with the indeno furanone synthesis featuring a
      C?O bond formation as the terminating step. This work demonstrates the power of
      ruthenium-catalyzed alkenylation as a platform reaction to develop more complex
      transformations, with multiple C?H functionalization steps taking place in a
      single operation to access novel carbocyclic structures. 

PMID- 24453064
TI  - A general strategy for assembling nanoparticles in one dimension.
AB  - Alignment of 1D assemblies of a wide variety of nanoparticles (e.g., metal, metal
      oxide, semiconductor quantum dots, or organic microspheres) in one direction upon
      diverse substrates (including industrial silicon wafers and transparent glass
      plates) by a general strategy is demonstrated. This sandwich method provides an
      efficient way of rapidly and precisely assembling nanoparticles on a large scale
      (up to 10 cm * 10 cm) for device applications. 

PMID- 24453065
TI  - Lactobacillus brevis OPK-3 isolated from kimchi inhibits adipogenesis and exerts
      anti-inflammation in 3T3-L1 adipocyte.
AB  - BACKGROUND: Kimchi is a traditional fermented food in Korea that contains various
      unique microorganisms. Diverse bacteria are involved in the process of Kimchi
      fermentation and the healthful advantages; one of the major species is
      Lactobacillus. We investigated whether lactic acid bacteria isolated from Kimchi
      (KLAB) are capable of reducing intracellular lipid accumulation by downregulating
      the expression of adipogenesis and lipogenesis promoting genes in differentiating
      3T3-L1 cells. RESULTS: KLAB (Lactobacillus brevis OPK-3) mediated dose-dependent
      inhibition of adipocyte differentiation, intracellular triglyceride accumulation
      and glycerol-3-phosphate dehydrogenase (GPDH) activity. The expression of
      transcription factors such as peroxisome proliferator-activated receptor gamma
      and CCAAT/enhancer-binding protein alpha involved in adipogenesis was markedly
      decreased by the KLAB treatment. Terminal adipogenic marker, e.g. adipocyte fatty
      acid binding protein (aP2), lipoprotein lipase, liver X receptor alpha, leptin
      and GPDH were significantly downregulated by KLAB treatment compared to untreated
      control. Moreover, cytokine genes, such as tumor necrosis factor-alpha and
      interleukin-6 mRNA expressions level were also decreased, whereas adiponectin
      mRNA level was upregulated by KLAB. CONCLUSION: These results suggest that the
      KLAB inhibits lipid accumulation in the differentiating adipocyte through
      downregulating the expression of adipogenic transcription factors and other
      specific genes involved in lipid metabolism.

PMID- 24453066
TI  - Identification of men with the highest risk of early disease recurrence after
      radical prostatectomy.
AB  - BACKGROUND: Men destined to have early biochemical recurrence (BCR) following
      radical prostatectomy (RP) may be optimal candidates for multimodal treatment.
      Here we identified pre-operative predictors of early BCR within a surgical cohort
      who recurred. METHODS: An institutional prostate cancer (PCa) database containing
      over 20,000 patients was queried to identify 1,471 men who had BCR after RP, and
      pre-operative predictors of early versus late BCR were assessed. Early BCR was
      defined as recurrence within 1 year after RP. Within the recurrence cohort, those
      with National Comprehensive Cancer Network (NCCN) high-risk features were more
      likely to experience early BCR. Therefore, in all NCCN high-risk men in the
      database, we abstracted detailed pathologic biopsy data. Among 753 high-risk men,
      41 alternate multivariable criteria were assessed for their ability to predict
      early BCR in crude and adjusted logistic regression models. RESULTS: The criteria
      that best identified those likely to experience early BCR are primary Gleason
      pattern 5 on biopsy or >=4 cores containing pattern 4 (odds ratio 3.17, P <
      0.001). These criteria included 26.7% of NCCN high-risk men. Additionally, these
      criteria selected for men within the high-risk classification who were at
      significantly higher risk of subsequent metastasis (adjusted hazard ratio 3.04, P
      < 0.001) and cancer-specific death (adjusted hazard ratio 3.27, P < 0.001).
      CONCLUSIONS: In men with PCa who present with high-risk features, pre-operative
      criteria have the ability to discriminate the subgroup most likely to experience
      early BCR after RP. Men at risk for early disease recurrence may be the most
      suitable candidates for multimodal therapy.

PMID- 24453067
TI  - Loss of GATA-1 full length as a cause of Diamond-Blackfan anemia phenotype.
AB  - Mutations in the hematopoietic transcription factor GATA-1 alter the
      proliferation/differentiation of hemopoietic progenitors. Mutations in exon 2
      interfere with the synthesis of the full-length isoform of GATA-1 and lead to the
      production of a shortened isoform, GATA-1s. These mutations have been found in
      patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia
      typically caused by mutations in genes encoding ribosomal proteins. We sequenced
      GATA-1 in 23 patients that were negative for mutations in the most frequently
      mutated DBA genes. One patient showed a c.2T > C mutation in the initiation codon
      leading to the loss of the full-length GATA-1 isoform.

PMID- 24453068
TI  - Endovascular repair of abdominal aortic aneurysm.
AB  - BACKGROUND: An abnormal dilatation of the abdominal aorta is referred to as an
      abdominal aortic aneurysm (AAA). Due to the risk of rupture, surgical repair is
      offered electively to individuals with aneurysms greater than 5.5 cm in size.
      Traditionally, conventional open surgical repair (OSR) was considered the first
      choice approach. However, over the past two decades endovascular aneurysm repair
      (EVAR) has gained popularity as a treatment option. This article intends to
      review the role of EVAR in the management of elective AAA. OBJECTIVES: To assess
      the effectiveness of EVAR versus conventional OSR in individuals with AAA
      considered fit for surgery, and EVAR versus best medical care in those considered
      unfit for surgery. This was determined by the effect on short, intermediate and
      long-term mortality, endograft related complications, re-intervention rates and
      major complications. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases
      Group Trials Search Co-ordinator (TSC) searched the Specialised Register (January
      2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012,
      Issue 12). The TSC also searched trial databases for details of ongoing or
      unpublished studies. SELECTION CRITERIA: Prospective randomised controlled trials
      (RCTs) comparing EVAR with OSR in individuals with AAA considered fit for
      surgery. and comparing EVAR with best medical care in individuals considered
      unfit for surgery. We excluded studies with inadequate data or using an
      inadequate randomisation technique. DATA COLLECTION AND ANALYSIS: Three reviewers
      independently evaluated trials for appropriateness for inclusion and extracted
      data using pro forma designed by the Cochrane PVD Group. We assessed the quality
      of trials using The Cochrane Collaboration's 'Risk of bias' tool. We entered
      collected data in to Review Manager (version 5.2.3) for analysis. Where direct
      comparisons could be made, we determined odds ratios (OR). We tested studies for
      heterogeneity and, when present, we used a random-effects model; otherwise we
      used a fixed-effect model. We tabulated data that could not be collated. MAIN
      RESULTS: Four high-quality trials comparing EVAR with OSR (n = 2790) and one high
      quality trial comparing EVAR with no intervention (n = 404) fulfilled the
      inclusion criteria. In individuals considered fit for surgery, a pooled analysis,
      including 1362 individuals randomised to EVAR and 1361 randomised to OSR, found
      short-term mortality (including 30-day or inhospital mortality, excluding deaths
      prior to intervention) with EVAR to be significantly lower than with OSR (1.4%
      versus 4.2%, OR 0.33, 95% confidence interval (CI) 0.20 to 0.55; P < 0.0001).
      Using intention-to-treat analysis (ITT) there was no significant difference in
      mortality at intermediate follow-up (up to four years from randomisation), with
      221 (15.8%) and 237 (17%) deaths in the EVAR (n = 1393) and OSR (n = 1390)
      groups, respectively (OR 0.92, 95% CI 0.75 to 1.12; P = 0.40). There was also no
      significant difference in long-term mortality (beyond four years), with 464
      (37.3%) deaths in the EVAR and 470 (37.8%) deaths in the OSR group (OR 0.98, 95%
      CI 0.83 to 1.15; P = 0.78). Similarly, there was no significant difference in
      aneurysm-related mortality between groups, either at the intermediate- or long
      term follow up.Studies showed that both EVAR and OSR were associated with similar
      incidences of cardiac deaths (OR 1.14, 95% CI 0.86 to 1.52; P = 0.36) and fatal
      stroke rate (OR 0.81, 95% CI 0.42 to 1.55; P = 0.52). The long-term
      reintervention rate was significantly higher in the EVAR group than in the OSR
      group (OR 1.98, 95% CI 1.12 to 3.51; P = 0.02; I(2) = 85%). Results of the
      reintervention analysis should be interpreted with caution due to significant
      heterogeneity. Operative complications, health-related quality of life and sexual
      dysfunction were generally comparable between the EVAR and OSR groups. However,
      there was a slightly higher incidence of pulmonary complications in the OSR group
      compared with the EVAR group (OR 0.36, 95% CI 0.17 to 0.75; P = 0.006).In
      individuals considered unfit for conventional OSR, the one included trial found
      no difference between the EVAR and no-intervention groups with regard to all
      cause mortality at final follow up, with 21.0 deaths per 100 person-years in the
      EVAR group and 22.1 deaths per 100 person years in the no-intervention group
      (adjusted hazard ratio (HR) with EVAR 0.99, 95% CI 0.78 to 1.27; P = 0.97).
      Aneurysm-related deaths were, however, significantly higher in the no
      intervention group than in the EVAR group (adjusted HR 0.53, 95% CI 0.32 to 0.89;
      P = 0.02). There was no difference in myocardial events (HR 1.07, 95% CI 0.60 to
      1.91) between the groups in this study. AUTHORS' CONCLUSIONS: In individuals
      considered fit for conventional surgery, EVAR was associated with lower short
      term mortality than OSR. However, this benefit from EVAR did not persist at the
      intermediate- and long-term follow ups. Individuals undergoing EVAR had a higher
      reintervention rate than those undergoing OSR. Most of the reinterventions
      undertaken following EVAR, however, were catheter-based interventions associated
      with low mortality. Operative complications, health-related quality of life and
      sexual dysfunction were generally comparable between EVAR and OSR. However, there
      was a slightly higher incidence of pulmonary complications in the OSR group than
      in the EVAR group.In individuals considered unfit for open surgery, the results
      of a single trial found no overall short- or long-term benefits of EVAR over no
      intervention with regard to all-cause mortality, but individuals may differ and
      individual preferences should always be taken into account.

PMID- 24453069
TI  - Effects of the commercial antiandrogen flutamide on the biomarkers of
      reproduction in male Murray rainbowfish (Melanotaenia fluviatilis).
AB  - The endocrine responses in male Murray rainbowfish (Melanotaenia fluviatilis)
      were evaluated after exposures to biologically active concentrations of the
      nonsteroidal pharmaceutical, flutamide. Fish were exposed to nominal
      concentrations of 125 ug/L, 250 ug/L, 500 ug/L, and 1000 ug/L of flutamide for 7
      d, after which plasma vitellogenin concentration; brain aromatase activity; and
      hepatic expression of the genes for vitellogenin, choriogenin, and androgen and
      estrogen receptors were assessed. Qualitative assessment of the testes of the
      fish exposed to flutamide exhibited hindrance in the transformation of
      spermatogonia to spermatozoa and increased testicular anomalies, such as
      multinucleated and pyknotic cells and interstitial fibrosis. An increase in the
      hepatosomatic index with respect to the controls was noted after treating the
      fish with flutamide at all concentrations. Vitellogenin was induced in plasma in
      the 1000 ug/L flutamide group. The activity of aromatase in the brain declined
      significantly after exposures to flutamide at all concentrations. Males exposed
      to 1000 ug/L of flutamide showed a downregulation in the genes encoding androgen
      receptors alpha and beta. The expression of the gene for the estrogen receptor
      alpha was induced and of vitellogenin was downregulated after treatment with 250
      ug/L to 1000 ug/L of flutamide. The results suggest that 7-d exposures to 125
      ug/L to 1000 ug/L flutamide can impair the reproductive endocrine system in male
      Murray rainbowfish at multiple levels by an antiandrogenic mode of action.

PMID- 24453070
TI  - Correcting Psychotherapists' Blindsidedness: Formal Feedback as a Means of
      Overcoming the Natural Limitations of Therapists.
AB  - PURPOSE: Monitoring of client progress in psychological therapy using formal
      outcome measures at each session has been shown to increase the effectiveness of
      treatment. It seems likely that this 'feedback' effect is achieved by enabling
      therapists to identify clients at risk of treatment failure so that therapists
      can pay greater attention to client difficulties, which may be hindering
      therapeutic work. To date, little attention has been given to understanding
      relevant mechanisms of formal feedback in psychological therapy. In order to
      understand and maximize the benefits of feedback, it is essential to explore
      potential mechanisms contributing to this effect. Research in social psychology
      may help to explain how feedback works. METHODS: Findings on cognitive biases in
      the field of social psychology are explored and linked to preliminary findings in
      the field of psychotherapy research. RESULTS: Research on cognitive biases and
      expertise is congruent with indications that clinical prediction in psychotherapy
      is unreliable and that it may be difficult for clinicians to detect errors in
      their judgement as a result of a lack of clear corrective feedback. This problem
      is linked to the fact that clinical outcomes occur in a complex 'noisy'
      environment where prediction is inherently difficult. CONCLUSION: Formal feedback
      may derive its benefits from its ability to help correct naturally occurring
      biases in therapists' assessment of their work. If these biases are seen as
      normal, but often avoidable if feedback is used, this may pave the way to greater
      acceptance of formal feedback by clinicians and enhanced outcomes for clients.
      KEY PRACTITIONER MESSAGE: The use of formal feedback tools can help therapists
      overcome inevitable limitations in their ability to predict poor response to
      treatment, enhancing the likelihood of detecting and resolving client
      difficulties in therapy.

PMID- 24453071
TI  - Variations of the tracheobronchial tree: anatomical and clinical significance.
AB  - Tracheobronchial variations can be found during routine bronchoscopy or computed
      tomography. Previous sources estimate an incidence of 1-12%; however, these
      variations are often asymptomatic. Symptomatic patients present typically with
      cough and lower respiratory tract infection. Knowledge and understanding of
      tracheobronchial variations have important implications for diagnosis of
      symptomatic patients and performing certain procedures, including bronchoscopy
      and endotracheal intubation. In this review, we describe the most commonly
      encountered variations, tracheal bronchus and accessory cardiac bronchus, along
      with three minor abnormalities of this region. We also review the various imaging
      modalities in the diagnosis and treatment of these conditions.

PMID- 24453072
TI  - Foxp2 regulates neuronal differentiation and neuronal subtype specification.
AB  - Mutations of the transcription factor FOXP2 in humans cause a severe speech and
      language disorder. Disruption of Foxp2 in songbirds or mice also leads to
      deficits in song learning or ultrasonic vocalization, respectively. These data
      suggest that Foxp2 plays important roles in the developing nervous system.
      However, the mechanism of Foxp2 in regulating neural development remains elusive.
      In the current study, we found that Foxp2 increased neuronal differentiation
      without affecting cell proliferation and cell survival in primary neural
      progenitors from embryonic forebrains. Foxp2 induced the expression of platelet
      derived growth factor receptor alpha, which mediated the neurognic effect of
      Foxp2. In addition, Foxp2 positively regulated the differentiation of medium
      spiny neurons derived from the lateral ganglionic eminence and negatively
      regulated the formation of interneurons derived from dorsal medial ganglionic
      eminence by interacting with the Sonic hedgehog pathway. Taken together, our
      results suggest that Foxp2 regulates multiple aspects of neuronal development in
      the embryonic forebrain.

PMID- 24453073
TI  - Increased topsoil carbon stock across China's forests.
AB  - Biomass carbon accumulation in forest ecosystems is a widespread phenomenon at
      both regional and global scales. However, as coupled carbon-climate models
      predicted, a positive feedback could be triggered if accelerated soil carbon
      decomposition offsets enhanced vegetation growth under a warming climate. It is
      thus crucial to reveal whether and how soil carbon stock in forest ecosystems has
      changed over recent decades. However, large-scale changes in soil carbon stock
      across forest ecosystems have not yet been carefully examined at both regional
      and global scales, which have been widely perceived as a big bottleneck in
      untangling carbon-climate feedback. Using newly developed database and
      sophisticated data mining approach, here we evaluated temporal changes in topsoil
      carbon stock across major forest ecosystem in China and analysed potential
      drivers in soil carbon dynamics over broad geographical scale. Our results
      indicated that topsoil carbon stock increased significantly within all of five
      major forest types during the period of 1980s-2000s, with an overall rate of 20.0
      g C m(-2) yr(-1) (95% confidence interval, 14.1-25.5). The magnitude of soil
      carbon accumulation across coniferous forests and coniferous/broadleaved mixed
      forests exhibited meaningful increases with both mean annual temperature and
      precipitation. Moreover, soil carbon dynamics across these forest ecosystems were
      positively associated with clay content, with a larger amount of SOC accumulation
      occurring in fine-textured soils. In contrast, changes in soil carbon stock
      across broadleaved forests were insensitive to either climatic or edaphic
      variables. Overall, these results suggest that soil carbon accumulation does not
      counteract vegetation carbon sequestration across China's forest ecosystems. The
      combination of soil carbon accumulation and vegetation carbon sequestration
      triggers a negative feedback to climate warming, rather than a positive feedback
      predicted by coupled carbon-climate models.

PMID- 24453074
TI  - Supramolecular protein assemblies in the nucleus of human cells.
AB  - Genetically encoded supramolecular protein assemblies (SMPAs) are induced to form
      in living cells by combination of distinct self-assembly properties. A single
      fusion construct contains genes encoding the heavy chain (H) of human ferritin
      and the citrine fluorescent protein, the latter exposing a weak dimerization
      interface, as well as a nuclear localization signal. Upon expression in HeLa
      cells, in vivo confocal fluorescence and differential interference contrast
      imaging revealed extended SMPA structures exclusively in the nuclei. Assemblies
      were typically round and took alveolar, shell-like, or hybrid structure.
      Transmission electron microscopy revealed a crystalline packing. Site-specific
      mutagenesis of the citrine dimerization interface clarified the mechanism of SMPA
      formation. The constituent proteins retained their activity in iron binding and
      fluorescence emission, thus suggesting a general strategy for formation of
      synthetic cellular bodies with specific biochemical function. 

PMID- 24453075
TI  - New insights into the nature of observable reaction intermediates in cytochrome
      P450 NO reductase by using a combination of spectroscopy and quantum
      mechanics/molecular mechanics calculations.
AB  - Cytochrome P450 NO reductase is an unusual member of the cytochrome P450
      superfamily. It catalyzes the reduction of nitric oxide to nitrous oxide. The
      reaction intermediates were studied in detail by a combination of experimental
      and computational methods. They have been characterized experimentally by UV/Vis,
      EPR, Mossbauer, and MCD spectroscopy. In conjunction with quantum
      mechanics/molecular mechanics (QM/MM) calculations, we sought to characterize the
      resting state and the two detectable intermediates in detail and to elucidate the
      nature of the key intermediate I of the reaction. Six possible candidates were
      taken into account for the unknown key intermediate in the computational study,
      differing in protonation state and electronic structure. Two out of the six
      candidates could be identified as putative intermediates I with the help of the
      spectroscopic data: singlet diradicals Fe(III)-NHO(.)(-) and Fe(III)-NHOH(.). In
      a companion publication (C. Riplinger, F. Neese, ChemPhysChem- 2011, 12, 3192) we
      have used QM/MM models based on these structures and performed a kinetic
      simulation. The combination of these two studies shows the nature of the key
      intermediate to be the singlet diradical, Fe(III)-NHOH(.).

PMID- 24453076
TI  - Naive CD4 T-cell activation identifies MS patients having rapid transition to
      progressive MS.
AB  - OBJECTIVE: Our objective was to determine whether altered naive CD4 T-cell
      biology contributes to development of disease progression in secondary
      progressive multiple sclerosis (SPMS). METHODS: We compared the naive CD4 T-cell
      gene expression profiles of 19 patients with SPMS and 14 healthy controls (HCs)
      using a whole-genome microarray approach. We analyzed surface protein expression
      of critical genes by flow cytometry after T-cell receptor (TCR) stimulation of
      naive CD4 T cells isolated from HCs and patients with SPMS. RESULTS: Hierarchical
      clustering segregated patients with SPMS into 2 subgroups: SP-1, which had a
      short duration of relapsing-remitting multiple sclerosis (MS), and SP-2, which
      had a long duration of relapsing-remitting MS. SP-1 patients upregulated numerous
      immune genes, including genes within TCR and toll-like receptor (TLR) signaling
      pathways. SP-2 patients showed immune gene downregulation in comparison with HCs.
      We identified an SP-1-specific transcriptional signature of 3 genes (TLR4, TLR2,
      and chemokine receptor 1), and these genes had higher surface protein expression
      in SP-1 than in SP-2. After TCR stimulation for 48 hours, only SP-1 showed a
      progressive linear increase in TLR2 and TLR4 protein expression. CONCLUSIONS:
      Differences in naive CD4 T-cell biology, notably of TCR and TLR signaling
      pathways, identified patients with MS with more rapid conversion to secondary
      progression, a critical determinant of long-term disability in MS.

PMID- 24453077
TI  - Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes:
      WHIMS-MRI study.
AB  - OBJECTIVE: To test whether red blood cell (RBC) levels of marine omega-3 fatty
      acids measured in the Women's Health Initiative Memory Study were related to MRI
      brain volumes measured 8 years later. METHODS: RBC eicosapentaenoic acid (EPA),
      docosahexaenoic acid (DHA), and MRI brain volumes were assessed in 1,111
      postmenopausal women from the Women's Health Initiative Memory Study. The
      endpoints were total brain volume and anatomical regions. Linear mixed models
      included multiple imputations of fatty acids and were adjusted for hormone
      therapy, time since randomization, demographics, intracranial volume, and
      cardiovascular disease risk factors. RESULTS: In fully adjusted models, a 1 SD
      greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm(3) larger
      brain volume (p = 0.048). DHA was marginally correlated (p = 0.063) with total
      brain volume while EPA was less so (p = 0.11). There were no correlations between
      ischemic lesion volumes and EPA, DHA, or EPA + DHA. A 1 SD greater omega-3 index
      was correlated with greater hippocampal volume (50 mm(3), p = 0.036) in fully
      adjusted models. Comparing the fourth quartile vs the first quartile of the omega
      3 index confirmed greater hippocampal volume (159 mm(3), p = 0.034). CONCLUSION:
      A higher omega-3 index was correlated with larger total normal brain volume and
      hippocampal volume in postmenopausal women measured 8 years later. While normal
      aging results in overall brain atrophy, lower omega-3 index may signal increased
      risk of hippocampal atrophy. Future studies should examine whether maintaining
      higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain
      atrophy.

PMID- 24453078
TI  - Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a
      phase 2 study.
AB  - OBJECTIVES: We present the first study to explore safety and efficacy of the
      human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple
      sclerosis (RRMS). METHODS: In this randomized, double-blind, placebo-controlled
      study, patients received 2 ofatumumab infusions (100 mg, 300 mg, or 700 mg) or
      placebo 2 weeks apart. At week 24, patients received alternate treatment. Safety
      and efficacy were assessed. RESULTS: Thirty-eight patients were randomized
      (ofatumumab/placebo, n = 26; placebo/ofatumumab, n = 12) and analyzed; 36
      completed the study. Two patients in the 300-mg group withdrew from the study
      because of adverse events. No unexpected safety signals emerged. Infusion-related
      reactions were common on the first infusion day but not observed on the second
      infusion day. None of the patients developed human anti-human antibodies.
      Ofatumumab was associated with profound selective reduction of B cells as
      measured by CD19(+) expression. New brain MRI lesion activity was suppressed
      (>99%) in the first 24 weeks after ofatumumab administration (all doses), with
      statistically significant reductions (p < 0.001) favoring ofatumumab found in new
      T1 gadolinium-enhancing lesions, total enhancing T1 lesions, and new and/or
      enlarging T2 lesions. CONCLUSIONS: Ofatumumab (up to 700 mg) given 2 weeks apart
      was not associated with any unexpected safety concerns and was well tolerated in
      patients with RRMS. MRI data suggest a clinically meaningful effect of ofatumumab
      for all doses studied. Results warrant further exploration of ofatumumab in RRMS.
      CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in
      patients with RRMS, ofatumumab compared with placebo does not increase the number
      of serious adverse events and decreases the number of new MRI lesions.

PMID- 24453079
TI  - Bezafibrate in skeletal muscle fatty acid oxidation disorders: a randomized
      clinical trial.
AB  - OBJECTIVE: To assess whether bezafibrate increases fatty acid oxidation (FAO) and
      lowers heart rate (HR) during exercise in patients with carnitine
      palmitoyltransferase (CPT) II and very long-chain acyl-CoA dehydrogenase (VLCAD)
      deficiencies. METHODS: This was a 3-month, randomized, double-blind, crossover
      study of bezafibrate in patients with CPT II (n = 5) and VLCAD (n = 5)
      deficiencies. Primary outcome measures were changes in FAO, measured with stable
      isotope methodology and indirect calorimetry, and changes in HR during exercise.
      RESULTS: Bezafibrate lowered low-density lipoprotein, triglyceride, and free
      fatty acid concentrations; however, there were no changes in palmitate oxidation,
      FAO, or HR during exercise. CONCLUSION: Bezafibrate does not improve clinical
      symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies.
      These findings indicate that previous in vitro studies suggesting a therapeutic
      potential for fibrates in disorders of FAO do not translate into clinically
      meaningful effects in vivo. CLASSIFICATION OF EVIDENCE: This study provides Class
      I evidence that bezafibrate 200 mg 3 times daily is ineffective in improving
      changes in FAO and HR during exercise in adults with CPT II and VLCAD
      deficiencies.

PMID- 24453081
TI  - Comment: should we induce ketosis in super-refractory status epilepticus?

PMID- 24453080
TI  - APOE epsilon4 worsens hippocampal CA1 apical neuropil atrophy and episodic
      memory.
AB  - OBJECTIVES: Using high-resolution structural MRI, we endeavored to study the
      relationships among APOE epsilon4, hippocampal subfield and stratal anatomy, and
      episodic memory. METHODS: Using a cross-sectional design, we studied 11 patients
      with Alzheimer disease dementia, 14 patients with amnestic mild cognitive
      impairment, and 14 age-matched healthy controls with no group differences in APOE
      epsilon4 carrier status. Each subject underwent ultra-high-field 7.0-tesla MRI
      targeted to the hippocampus and neuropsychological assessment. RESULTS: We found
      a selective, dose-dependent association of APOE epsilon4 with greater thinning of
      the CA1 apical neuropil, or stratum radiatum/stratum lacunosum-moleculare (CA1
      SRLM), a hippocampal subregion known to exhibit early vulnerability to
      neurofibrillary pathology in Alzheimer disease. The relationship between the
      epsilon4 allele and CA1-SRLM thinning persisted after controlling for dementia
      severity, and the size of other hippocampal subfields and the entorhinal cortex
      did not differ by APOE epsilon4 carrier status. Carriers also exhibited worse
      episodic memory function but similar performance in other cognitive domains
      compared with noncarriers. In a statistical mediation analysis, we found support
      for the hypothesis that CA1-SRLM thinning may link the APOE epsilon4 allele to
      its phenotypic effects on memory. CONCLUSIONS: The APOE epsilon4 allele
      segregated dose-dependently and selectively with CA1-SRLM thinning and worse
      episodic memory performance in a pool of older subjects across a cognitive
      spectrum. These findings highlight a possible role for this gene in influencing a
      critical hippocampal subregion and an associated symptomatic manifestation.

PMID- 24453082
TI  - Abnormal metabolic network activity in REM sleep behavior disorder.
AB  - OBJECTIVE: To determine whether the Parkinson disease-related covariance pattern
      (PDRP) expression is abnormally increased in idiopathic REM sleep behavior
      disorder (RBD) and whether increased baseline activity is associated with greater
      individual risk of subsequent phenoconversion. METHODS: For this cohort study, we
      recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects
      with RBD (63.5 +/- 9.4 years old) and 10 healthy volunteers (62.7 +/- 8.6 years
      old) who underwent resting-state metabolic brain imaging with (18)F
      fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 +/- 4.8
      years old) and 17 healthy volunteers (66.6 +/- 6.0 years old) who underwent
      resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter
      group was followed clinically for 4.6 +/- 2.5 years by investigators blinded to
      the imaging results. PDRP expression was measured in both RBD groups and compared
      with corresponding control values. RESULTS: PDRP expression was elevated in both
      groups of subjects with RBD (cohort 1: p < 0.04; cohort 2: p < 0.005). Of the 17
      subjects with long-term follow-up, 8 were diagnosed with Parkinson disease or
      dementia with Lewy bodies; the others did not phenoconvert. For individual
      subjects with RBD, final phenoconversion status was predicted using a logistical
      regression model based on PDRP expression and subject age at the time of imaging
      (r(2) = 0.64, p < 0.0001). CONCLUSIONS: Latent network abnormalities in subjects
      with idiopathic RBD are associated with a greater likelihood of subsequent
      phenoconversion to a progressive neurodegenerative syndrome.

PMID- 24453083
TI  - Ketogenic diet for adults in super-refractory status epilepticus.
AB  - OBJECTIVE: To describe a case series of adult patients in the intensive care unit
      in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours
      or more despite appropriate anesthetic treatment) who received treatment with the
      ketogenic diet (KD). METHODS: We performed a retrospective case review at 4
      medical centers of adult patients with SRSE treated with the KD. Data collected
      included demographic features, clinical presentation, diagnosis, EEG data,
      anticonvulsant treatment, and timing and duration of the KD. Primary outcome
      measures were resolution of status epilepticus (SE) after initiation of KD and
      ability to wean from anesthetic agents. RESULTS: Ten adult patients at 4 medical
      centers were started on the KD for SRSE. The median age was 33 years
      (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had
      encephalitis. The median duration of SE before initiation of KD was 21.5 days
      (IQR 28) and the median number of antiepileptic medications used before
      initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and
      SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three
      patients had minor complications of the KD including transient acidosis and
      hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the
      KD. CONCLUSION: We describe treatment of critically ill adult patients with SRSE
      with the KD, with 90% of patients achieving resolution of SE. Prospective trials
      are warranted to examine the efficacy of the KD in adults with refractory SE.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for
      intensive care unit patients with refractory SE, a KD leads to resolution of the
      SE.

PMID- 24453084
TI  - Age is not a prognostic factor in children with Wilms tumor beyond stage I in
      Africa.
AB  - BACKGROUND: Patients under age 4 with stage I favorable histology (FH) Wilms
      tumor have a reported survival advantage. Among children above 10 years, a poorer
      prognosis has been associated with a higher prevalence of diffuse anaplasia.
      PURPOSE: To determine if, in our practice, patients with Wilms tumors >8 years of
      age (stage II-V) have a poorer prognosis than those aged <8 years or <4 years.
      PROCEDURE: Case-control study of 19 patients >8 years with Wilms tumor stages II
      V who were identified from a cohort of 192 new patients (2002-2012). For each
      patient two controls were chosen matched for stage and histology, one 0-3 years
      and one 4-7 years. Neo-adjuvant chemotherapy was offered to all, combined with
      intensive supportive care. Postoperative treatment was determined by local stage
      and histology. OS and EFS at 5 years for the different age groups were compared.
      RESULTS: Each age group contained 19 patients, of whom 6 had stage II tumors, 3
      stage III, 8 stage IV, and 2 stage V. Histology was intermediate risk (IR) in 17
      and high risk (HR) in 2. OS at 5 years was 80.8% and EFS was 79.2% for the whole
      group. No significant difference in outcome could be shown between age groups.
      Loss to follow up was 6/57 (11%). CONCLUSIONS: The survival advantage of young
      age (<4 years) associated with stage I FH could not be demonstrated in higher
      stages. Age had no significant impact on prognosis although a trend to better
      outcome was seen in children <4 years.

PMID- 24453085
TI  - Novel anticoagulants in patients with mechanical heart valves.

PMID- 24453086
TI  - Percutaneous coronary intervention of culprit and non-culprit coronary arteries
      in acute ST-elevation MI may improve outcomes.

PMID- 24453087
TI  - Neither ibuprofen nor steam improves symptom control compared with paracetamol in
      patients with acute respiratory tract infections in primary care.

PMID- 24453088
TI  - Neither anti-inflammatory nor antibiotic treatment significantly shortens
      duration of cough in acute bronchitis compared with placebo.

PMID- 24453090
TI  - Factors controlling transport of graphene oxide nanoparticles in saturated sand
      columns.
AB  - The authors conducted column experiments and a modeling study to understand the
      effects of several environmental factors on the aggregation and transport of
      graphene oxide nanoparticles (GONPs) in saturated quartz sand. The GONPs were
      negatively charged and stable under the test conditions (0-50 mM NaCl; pH 4.8
      9.0), and the Derjaguin-Landau-Verwey-Overbeek (DLVO) calculation indicated that
      deposition of GONPs was under unfavorable attachment conditions. The GONPs
      exhibited high mobility even at an ionic strength of 25 mM NaCl. The transport of
      GONPs was insensitive to the changes of pH (from 5.1 to 9.0), but the presence of
      10 mg/L Suwannee River humic acid (SRHA) considerably enhanced transport at high
      ionic strength (35 mM NaCl), likely via enhanced steric repulsion and
      significantly inhibited stacking of GO flakes. Varying flow velocity also
      enhanced transport at high ionic strength. In general, GONPs exhibit greater
      mobility compared with other carbon nanoparticles because the aggregation and
      transport of GONPs are more resilient to changes in solution chemistry and
      hydrodynamic forces that favor aggregation and deposition of nanoparticles. A 2
      site transport model incorporating both the blocking-affected attachment process
      and straining effects can effectively model the transport of GONPs. The high
      mobility of GONPs should be given full consideration in assessing their
      environmental risks.

PMID- 24453089
TI  - Neurodevelopmental alterations of large-scale structural networks in children
      with new-onset epilepsy.
AB  - Recent neuroimaging and behavioral studies have revealed that children with new
      onset epilepsy already exhibit brain structural abnormalities and cognitive
      impairment. How the organization of large-scale brain structural networks is
      altered near the time of seizure onset and whether network changes are related to
      cognitive performances remain unclear. Recent studies also suggest that regional
      brain volume covariance reflects synchronized brain developmental changes. Here,
      we test the hypothesis that epilepsy during early-life is associated with
      abnormalities in brain network organization and cognition. We used graph theory
      to study structural brain networks based on regional volume covariance in 39
      children with new-onset seizures and 28 healthy controls. Children with new-onset
      epilepsy showed a suboptimal topological structural organization with enhanced
      network segregation and reduced global integration compared with controls. At the
      regional level, structural reorganization was evident with redistributed nodes
      from the posterior to more anterior head regions. The epileptic brain network was
      more vulnerable to targeted but not random attacks. Finally, a subgroup of
      children with epilepsy, namely those with lower IQ and poorer executive function,
      had a reduced balance between network segregation and integration. Taken
      together, the findings suggest that the neurodevelopmental impact of new onset
      childhood epilepsies alters large-scale brain networks, resulting in greater
      vulnerability to network failure and cognitive impairment.

PMID- 24453091
TI  - Discovery of inhibitors of Shiga toxin type 2 by on-plate generation and
      screening of a focused compound library.
AB  - A new microtiter-plate-based method for the rapid generation and evaluation of
      focused compound libraries was developed and applied to screening ligand
      analogues for the E. coli Shiga-like toxin Stx2a. The method is general, it
      mitigates the masking of intrinsic affinity gains by multivalency and enables the
      discovery of potential hits when starting from ligands that exhibit extremely low
      affinity with proteins that depend on multivalency for their function. 

PMID- 24453092
TI  - Assessment of different mouthwashes on cannabis oral fluid concentrations.
AB  - Since the implementation of mandatory drug testing in drivers' oral fluid,
      several solutions to avoid an onsite positive result can be found on drug users'
      forums, especially for marijuana, including the use of different mouthwashes.
      Recently, a product for personal hygiene, Kleaner, has been sold for this
      purpose. The aims of this study were to assess the effect of water, whole milk,
      and Kleaner mouthwashes on tetrahydrocannabinol (THC) oral fluid concentrations,
      and those observed in passive smokers subjected to extreme contamination
      conditions. The study was performed on four days. On day 0, study information was
      given to the participants. On days 1, 2, and 3, 11 chronic cannabis users smoked
      their usual daily dose, and oral fluid specimens were collected before smoking
      (t=-0.5h) and at t=0.25, 0.5, 1, 3, 6, 12, and 24 h post-smoking. On day 1,
      participants rinsed their mouth with water before each specimen collection. On
      day 2, 5 participants rinsed their mouth with Kleaner and 6 with whole milk. On
      day 3, a specimen was collected before and after rinsing the mouth with water.
      Statistically significant lower concentrations were observed comparing
      concentrations in oral fluid specimens collected before and after a water rinse.
      However, maximum THC concentrations at t=0.25 h were >3-fold higher than the cut
      off employed by the Spanish police (25 ng/mL) regardless of the use of any
      mouthwash. THC was also detected in the oral fluid of passive smokers subjected
      to extreme contamination conditions; however, concentrations were <25 ng/mL in
      all cases.

PMID- 24453093
TI  - Evidence-based co-medication in heart failure: necessary or bystander?
AB  - This article refers to 'Impact of aspirin and statins on longterm survival in
      patients with acute myocardial infarction complicated by heart failure: an
      analysis in 1746 patients' by C. Lewinter et al., published in this issue on page
      95-102.

PMID- 24453094
TI  - Why and when should we worry about worsening renal function?

PMID- 24453095
TI  - Meeting highlights from the 2013 European Society of Cardiology Heart Failure
      Association Winter Meeting on Translational Heart Failure Research.

PMID- 24453096
TI  - Analysing recurrent hospitalizations in heart failure: a review of statistical
      methodology, with application to CHARM-Preserved.
AB  - AIMS: Heart failure is characterized by recurrent hospitalizations, but often
      only the first event is considered in clinical trial reports. In chronic
      diseases, such as heart failure, analysing all events gives a more complete
      picture of treatment benefit. We describe methods of analysing repeat
      hospitalizations, and illustrate their value in one major trial. METHODS AND
      RESULTS: The Candesartan in Heart failure Assessment of Reduction in Mortality
      and morbidity (CHARM)-Preserved study compared candesartan with placebo in 3023
      patients with heart failure and preserved systolic function. The heart failure
      hospitalization rates were 12.5 and 8.9 per 100 patient-years in the placebo and
      candesartan groups, respectively. The repeat hospitalizations were analysed using
      the Andersen-Gill, Poisson, and negative binomial methods. Death was incorporated
      into analyses by treating it as an additional event. The win ratio method and a
      method that jointly models hospitalizations and mortality were also considered.
      Using repeat events gave larger treatment benefits than time to first event
      analysis. The negative binomial method for the composite of recurrent heart
      failure hospitalizations and cardiovascular death gave a rate ratio of 0.75 [95%
      confidence interval (CI) 0.62-0.91, P = 0.003], whereas the hazard ratio for time
      to first heart failure hospitalization or cardiovascular death was 0.86 (95% CI
      0.74-1.00, P = 0.050). CONCLUSIONS: In patients with preserved EF, candesartan
      reduces the rate of admissions for worsening heart failure, to a greater extent
      than apparent from analysing only first hospitalizations. Recurrent events should
      be routinely incorporated into the analysis of future clinical trials in heart
      failure.

PMID- 24453097
TI  - Worsening renal function during renin-angiotensin-aldosterone system inhibitor
      initiation and long-term outcomes in patients with left ventricular systolic
      dysfunction.
AB  - AIMS: Impaired renal function is associated with worse clinical outcomes in
      patients with LV systolic dysfunction (LVSD) and heart failure. Renin-angiotensin
      aldosterone system (RAAS) inhibitors provide clinical benefit in these settings
      and often worsen renal function. It is not clear whether worsening renal function
      (WRF) in patients exposed to these agents predicts a worse prognosis or merely
      reflects the pharmacological action of the drug on the kidney. METHODS AND
      RESULTS: We performed a meta-analysis of all RAAS inhibitor LVSD trials reporting
      on outcomes according to WRF (as per individual study definition) in both active
      intervention and placebo groups. Five major studies (SOLVD, SAVE, RALES, Val-HeFT
      and EPHESUS) contributed, with 20 573 patients. Compared with placebo, RAAS
      inhibitors reduced all-cause mortality overall [n = 20 573, relative risk ratio
      (RR) 0.91, 95% confidence interval (CI) 0.86-0.95, P = 0.0003], in the group with
      no WRF (n = 18 209, RR 0.91, 95% CI 0.83-0.99, P = 0.04), and in the WRF group (n
      = 2364, RR 0.72, 95% CI 0.62-0.84, P < 0.0001). Compared with no WRF, WRF was
      associated with increased all-cause mortality; however, this was less in the RAAS
      inhibitor group (n = 8905, RR 1.22, 95% CI 1.10-1.36, P = 0.0003) than in the
      placebo group (n = 9304, RR 1.52, 95% CI 1.37-1.69, P < 0.00001). CONCLUSIONS:
      WRF shortly after randomization is associated with worsened outcomes compared
      with no WRF; however, the reduction in all-cause mortality associated with the
      use of RAAS inhibitors was significantly greater in the presence of WRF than in
      the no WRF group. Clinicians should not be deterred from using RAAS inhibitors in
      the setting of WRF.

PMID- 24453098
TI  - Impact of aspirin and statins on long-term survival in patients hospitalized with
      acute myocardial infarction complicated by heart failure: an analysis of 1706
      patients.
AB  - AIMS: Aspirin and statins are established therapies for acute myocardial
      infarction (MI), but their benefits in patients with chronic heart failure (HF)
      remain elusive. We investigated the impact of aspirin and statins on long-term
      survival in patients hospitalized with acute MI complicated by HF. METHODS AND
      RESULTS: Of 4251 patients in the Evaluation of Methods and Management of Acute
      Coronary Events (EMMACE)-1 and -2 observational studies, 1706 patients had HF. A
      propensity score-matching method estimated the average treatment effects (ATEs)
      of aspirin and statins on survival over 90 months. ATEs were calculated as
      relative risk differences in all-cause mortality comparing patients receiving
      aspirin and statins with controls, respectively. Moreover, combined aspirin and
      statins vs. none (ATE I), aspirin or statins vs. none (ATE II), and aspirin and
      statins vs. aspirin or statins (ATE III) were assessed. The median survival times
      of the ATE I, ATE II and ATE III were 25, 50, and 85 months, respectively.
      Regarding aspirin, the ATE was significantly improved at 6, 12, and 90 months
      [ATE 6 months: 10%, 95% confidence interval (CI) 3-18%], where the ATE of statins
      favoured survival at 1-24 months (ATE 1 month: 5%, 95% CI 0.3-10%). Mortality was
      lower at 1, 6, and 24 months in those who received aspirin and statins (ATE I).
      When the combination was compared with either treatment alone, an effect
      persisted between 6 and 90 months (ATE III). CONCLUSION: In patients with acute
      MI complicated by HF, prescription of aspirin and statins either alone or
      together was associated with better long-term survival.

PMID- 24453099
TI  - Co-morbidities in patients with heart failure: an analysis of the European Heart
      Failure Pilot Survey.
AB  - AIMS: Co-morbidities frequently accompany heart failure (HF), contributing to
      increased morbidity and mortality, and an impairment of quality of life. We
      assessed the prevalence, determinants, regional variation, and prognostic
      implications of co-morbidities in patients with chronic HF in Europe. METHODS AND
      RESULTS: A total of 3226 European outpatients with chronic HF were included in
      this analysis of the European Society of Cardiology (ESC) Heart Failure Pilot
      Survey. The following co-morbidities were considered: diabetes, hyper- and
      hypothyroidism, stroke, COPD, sleep apnoea, chronic kidney disease (CKD), and
      anaemia. Prognostic implications of co-morbidities were evaluated using
      population attributable risks (PARs), and patients were divided into geographic
      regions. Clinical endpoints were all-cause mortality and HF hospitalization. The
      majority of patients (74%) had a least one co-morbidity, the most prevalent being
      CKD (41%), anaemia (29%), and diabetes (29%). Co-morbidities were independently
      associated with higher age (P < 0.001), higher NYHA functional class (P < 0.001),
      ischaemic aetiology of HF (P < 0.001), higher heart rate (P = 0.011), history of
      hypertension (P < 0.001), and AF (P < 0.001). Only diabetes, CKD, and anaemia
      were independently associated with a higher risk of mortality and/or HF
      hospitalization. There were marked regional differences in prevalence and
      prognostic implications of co-morbidities. Prognostic implications of co
      morbidities (PARs) were: CKD = 41%, anaemia = 37%, diabetes = 14%, COPD = 10%,
      and <10% for all other co-morbidities. CONCLUSION: In this pilot survey, co
      morbidities are prevalent in patients with chronic HF and are related to the
      severity of the disease. The presence of diabetes, CKD, and anaemia was
      independently related to increased mortality and HF hospitalization, with the
      highest PAR for CKD and anaemia.

PMID- 24453100
TI  - Is microvolt T-wave alternans testing suitable for patients recently hospitalized
      due to decompensated heart failure?

PMID- 24453101
TI  - Microvolt T-wave alternans testing in patients recently hospitalized with
      decompensated heart failure.

PMID- 24453102
TI  - Complete atrioventricular block DOES reduce mortality in patients with atrial
      fibrillation treated with cardiac resynchronization therapy.

PMID- 24453103
TI  - Complete atrioventricular block does reduce mortality in patients with atrial
      fibrillation treated with cardiac resynchronization therapy: reply.

PMID- 24453104
TI  - The development of a core syllabus for the teaching of head and neck anatomy to
      medical students.
AB  - The study of human anatomy has traditionally served as a fundamental component in
      the basic science education of medical students, yet there exists a remarkable
      lack of firm guidance on essential features that must be included in a gross
      anatomy course, which would constitute a "Core Syllabus" of absolutely mandatory
      structures and related clinical pathologies. While universal agreement on the
      details of a core syllabus is elusive, there is a general consensus that a core
      syllabus aims to identify the minimum level of knowledge expected of recently
      qualified medical graduates in order to carry out clinical procedures safely and
      effectively, while avoiding overloading students with unnecessary facts that have
      less immediate application to their future careers as clinicians. This paper aims
      to identify consensus standards of essential features of Head and Neck anatomy
      via a Delphi Panel consisting of anatomists and clinicians who evaluated syllabus
      content structures (greater than 1,000) as "essential", "important",
      "acceptable", or "not required." The goal is to provide guidance for
      program/course directors who intend to provide the optimal balance between
      establishing a comprehensive list of clinically relevant essential structures and
      an overwhelming litany, which would otherwise overburden trainees in their
      initial years of medical school with superficial rote learning, which potentially
      dilutes the key and enduring fundamental lessons that prepare students for
      training in any medical field.

PMID- 24453105
TI  - Cost minimization analysis of two treatment regimens for low-risk
      rhabdomyosarcoma in children: a report from the Children's Oncology Group.
AB  - BACKGROUND: Recent Children's Oncology Group trials for low-risk rhabdomyosarcoma
      attempted to reduce therapy while maintaining excellent outcomes. D9602 delivered
      45 weeks of outpatient vincristine and dactinomycin (VA) for patients in Subgroup
      A. ARST0331 reduced the duration of therapy to 22 weeks but added four doses of
      cyclophosphamide to VA for patients in Subset 1. Failure-free survival was
      similar. We undertook a cost minimization comparison to help guide future
      decision-making. PROCEDURE: Addressing the costs of treatment from the healthcare
      perspective we modeled a simple decision-analytic model from aggregate clinical
      trial data. Medical care inputs and probabilities were estimated from trial
      reports and focused chart review. Costs of radiation, surgery and off-therapy
      surveillance were excluded. Unit costs were obtained from literature and national
      reimbursement and inpatient utilization databases and converted to 2012 US
      dollars. Model uncertainty was assessed with first-order sensitivity analysis.
      RESULTS: Direct medical costs were $46,393 for D9602 and $43,261 for ARST0331
      respectively, making ARST0331 the less costly strategy. Dactinomycin contributed
      the most to D9602 total costs but varied with age (42-69%). Chemotherapy
      administration costs accounted for the largest proportion of ARST0331 total costs
      (39-57%). ARST0331 incurred fewer costs than D9602 under most alternative
      distributive models and alternative clinical practice assumptions. CONCLUSIONS:
      Cost analysis suggests that ARST0331 may incur fewer costs than D9602 from the
      healthcare system's perspective. Attention to the services driving the costs
      provides directions for future efficiency improvements. Future studies should
      prospectively consider the patient and family's perspective.

PMID- 24453106
TI  - Insights into the tautomerism in meso-substituted corroles: a variable
      temperature 1H, 13C, 15N, and 19F NMR spectroscopy study.
AB  - Tris(pentafluorophenyl)corrole and its (15)N-enriched isotopomer were studied in
      [D8]toluene solution by 1D and 2D variable-temperature NMR techniques to
      establish the mechanisms of tautomerization of the NH protons inside the interior
      of the corrole macrocycle. Three such rate processes could be identified of which
      two modulate the spectral line shapes at temperatures above 205 K and the third
      is NMR-inaccessible as it is very fast. The latter involves the proton engaged in
      an unsymmetrical proton sponge unit formed by two pyrrole nitrogen atoms.
      Temperature and concentration dependences of the two remaining processes were
      determined. One of them is purely intramolecular and the other is intermolecular
      at low temperatures, with growing contribution of an intramolecular mechanism at
      elevated temperatures. The proposed microscopic mechanisms of all these processes
      are semi-quantitatively confirmed by quantum chemical calculations using density
      functional theory.

PMID- 24453108
TI  - Modeling and correction of bolus dispersion effects in dynamic susceptibility
      contrast MRI.
AB  - PURPOSE: Bolus dispersion in DSC-MRI can lead to errors in cerebral blood flow
      (CBF) estimation by up to 70% when using singular value decomposition analysis.
      However, it might be possible to correct for dispersion using two alternative
      methods: the vascular model (VM) and control point interpolation (CPI).
      Additionally, these approaches potentially provide a means to quantify the
      microvascular residue function. METHODS: VM and CPI were extended to correct for
      dispersion by means of a vascular transport function. Simulations were performed
      at multiple dispersion levels and an in vivo analysis was performed on a healthy
      subject and two patients with carotid atherosclerotic disease. RESULTS:
      Simulations showed that methods that could not address dispersion tended to
      underestimate CBF (ratio in CBF estimation, CBFratio = 0.57-0.77) in the presence
      of dispersion; whereas modified CPI showed the best performance at low-to-medium
      dispersion; CBFratio = 0.99 and 0.81, respectively. The in vivo data showed
      trends in CBF estimation and residue function that were consistent with the
      predictions from simulations. CONCLUSION: In patients with atherosclerotic
      disease the estimated residue function showed considerable differences in the
      ipsilateral hemisphere. These differences could partly be attributed to
      dispersive effects arising from the stenosis when dispersion corrected CPI was
      used. It is thus beneficial to correct for dispersion in perfusion analysis using
      this method.

PMID- 24453107
TI  - Prefrontal transcranial direct current stimulation alters activation and
      connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation
      technique used both experimentally and therapeutically to modulate regional brain
      function. However, few studies have directly measured the aftereffects of tDCS on
      brain activity or examined changes in task-related brain activity consequent to
      prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI
      data from 22 human subjects, both at rest and while performing the Balloon Analog
      Risk Task (BART), before and after true or sham transcranial direct current
      stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and
      the right caudate and increased task-related activity in the right dorsolateral
      prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to
      losses but not wins or increasing risk. Network analysis showed that whole-brain
      connectivity of the right ACC correlated positively with the number of pumps
      subjects were willing to make on the BART, and that tDCS reduced connectivity
      between the right ACC and the rest of the brain. Whole-brain connectivity of the
      right DLPFC also correlated negatively with pumps on the BART, as prior
      literature would suggest. Our results suggest that tDCS can alter activation and
      connectivity in regions distal to the electrodes.

PMID- 24453109
TI  - Large hexagonal bi- and trilayer graphene single crystals with varied interlayer
      rotations.
AB  - Bi- and trilayer graphene have attracted intensive interest due to their rich
      electronic and optical properties, which are dependent on interlayer rotations.
      However, the synthesis of high-quality large-size bi- and trilayer graphene
      single crystals still remains a challenge. Here, the synthesis of 100 MUm pyramid
      like hexagonal bi- and trilayer graphene single-crystal domains on Cu foils using
      chemical vapor deposition is reported. The as-produced graphene domains show
      almost exclusively either 0 degrees  or 30 degrees  interlayer rotations. Raman
      spectroscopy, transmission electron microscopy, and Fourier-transformed infrared
      spectroscopy were used to demonstrate that bilayer graphene domains with 0
      degrees  interlayer stacking angles were Bernal stacked. Based on first-principle
      calculations, it is proposed that rotations originate from the graphene
      nucleation at the Cu step, which explains the origin of the interlayer rotations
      and agrees well with the experimental observations. 

PMID- 24453111
TI  - Tongue lesions.

PMID- 24453110
TI  - Peptide ligands stabilized by small molecules.
AB  - Bicyclic peptides generated through directed evolution by using phage display
      offer an attractive ligand format for the development of therapeutics. Being
      nearly 100-fold smaller than antibodies, they promise advantages such as access
      to chemical synthesis, efficient diffusion into tissues, and needle-free
      application. However, unlike antibodies, they do not have a folded structure in
      solution and thus bind less well. We developed bicyclic peptides with hydrophilic
      chemical structures at their center to promote noncovalent intramolecular
      interactions, thereby stabilizing the peptide conformation. The sequences of the
      peptides isolated by phage display from large combinatorial libraries were
      strongly influenced by the type of small molecule used in the screen, thus
      suggesting that the peptides fold around the small molecules. X-ray structure
      analysis revealed that the small molecules indeed formed hydrogen bonds with the
      peptides. These noncovalent interactions stabilize the peptide-protein complexes
      and contribute to the high binding affinity. 

PMID- 24453112
TI  - Is electrostatics sufficient to describe hydrogen-bonding interactions?
AB  - The stability and geometry of a hydrogen-bonded dimer is traditionally attributed
      mainly to the central moiety A-H???B, and is often discussed only in terms of
      electrostatic interactions. The influence of substituents and of interactions
      other than electrostatic ones on the stability and geometry of hydrogen-bonded
      complexes has seldom been addressed. An analysis of the interaction energy in the
      water dimer and several alcohol dimers--performed in the present work by using
      symmetry-adapted perturbation theory--shows that the size and shape of
      substituents strongly influence the stabilization of hydrogen-bonded complexes.
      The larger and bulkier the substituents are, the more important the attractive
      dispersion interaction is, which eventually becomes of the same magnitude as the
      total stabilization energy. Electrostatics alone are a poor predictor of the
      hydrogen-bond stability trends in the sequence of dimers investigated, and in
      fact, dispersion interactions predict these trends better.

PMID- 24453113
TI  - Concurrent stable and unstable cortical correlates of human wrist movements.
AB  - Cortical activity has been shown to correlate with different parameters of
      movement. However, the dynamic properties of cortico-motor mappings still remain
      unexplored in humans. Here, we show that during the repetition of simple
      stereotyped wrist movements both stable and unstable correlates simultaneously
      emerge in human sensorimotor cortex. Using visual feedback of wrist movement
      target inferred online from MEG, we assessed the dynamics of the tuning
      properties of two neuronal signals: the MEG signal below 1.6 Hz and within the 4
      to 6 Hz range. We found that both components are modulated by wrist movement
      allowing for closed-loop inference of movement targets. Interestingly, while
      tuning of 4 to 6 Hz signals remained stable over time leading to stable inference
      of movement target using a static classifier, the tuning of cortical signals
      below 1.6 Hz significantly changed resulting in steadily decreasing inference
      accuracy. Our findings demonstrate that non-invasive neuronal population signals
      in human sensorimotor cortex can reflect a stable correlate of voluntary
      movements. Hence, we provide first evidence for a stable control signal in non
      invasive human brain-machine interface research. However, as not all neuronal
      signals initially tuned to movement were stable across days, a careful selection
      of features for real-life applications seems to be mandatory.

PMID- 24453114
TI  - Mannose binding lectin and ficolin-2 polymorphisms are associated with increased
      risk for bacterial infections in children with B acute lymphoblastic leukemia.
AB  - BACKGROUND: We aimed to investigate whether the presence of mannose binding
      lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency
      significantly influence the risk and subsequently the frequency of chemotherapy
      induced bacterial infections in children with B acute lymphoblastic leukemia (B
      ALL). PROCEDURE: MBL2 polymorphisms for exon 1 and FCN2 polymorphisms for
      promoter regions -986, -602, -557, -64, -4 and exon 8 regions +6,359, +6,424 were
      determined in children with B-ALL. FCN2 haplotype was determined by gene
      sequencing. Number and duration of FN episodes as well as number of bacterial
      infections were recorded during induction chemotherapy. RESULTS: Forty-four
      children with B-ALL (median age 4.3 years, 65.9% males) suffered from 142 FN
      episodes and 92 bacterial infections (40.2% Gram positive and 59.8% Gram
      negative). MBL2 low-risk genotype was found in 59.1%, medium-risk in 31.8% and
      high-risk in 9%. FCN2 low-risk haplotypes were detected in 38.2%, medium-risk in
      44.1% and high-risk in 17.6%. MBL2 genotype and FCN2 haplotype were not
      associated with increased frequency of FN episodes. MBL2 medium/high-risk
      genotype and FCN2 medium/high-risk haplotype were associated with prolonged
      duration of FN (P = 0.007 and P = 0.001, respectively) and increased number of
      bacterial infections (P = 0.001 and P = 0.002, respectively). The combined
      MBL2/FCN2 medium/high-risk genotype was associated with an increased number of
      bacterial infections (P = 0.001). CONCLUSIONS: MBL2 and FCN2 single or combined
      deficiencies are associated with increased duration of FN episodes as well as
      increased number of bacterial infections in children with B-ALL suggesting a
      prognostic role of these genes.

PMID- 24453115
TI  - Peierls-distorted monoclinic MnB(4) with a Mn-Mn bond.
AB  - Tetraborides of chromium and manganese exhibit an unusual boron-atom framework
      that resembles the hypothetical tetragonal diamond. They are believed to be very
      hard. Single crystals of MnB4 have now been grown. The compound crystallizes in
      the monoclinic crystal system (space group P21 /c) with a structure that has four
      crystallographically independent boron-atom positions, as confirmed by (11) B MAS
      NMR spectroscopy. An unexpected short distance between the Mn atoms suggests a
      double Mn-Mn bond and is caused by Peierls distortion. The structure was solved
      using group-subgroup-relationships. DFT calculations indicate Mn(I) centers and
      paramagnetism, as confirmed by magnetic measurements. The density of states shows
      a pseudo-band gap at the Fermi energy and semiconducting behavior was observed
      for MnB4 . 

PMID- 24453116
TI  - 3DQRS: a method to obtain reliable QRS complex detection within high field MRI
      using 12-lead electrocardiogram traces.
AB  - PURPOSE: To develop a technique that accurately detects the QRS complex in 1.5
      Tesla (T), 3T, and 7T MRI scanners. METHODS: During early systole, blood is
      rapidly ejected into the aortic arch, traveling perpendicular to the MRI's main
      field, which produces a strong voltage (V(MHD)) that eclipses the QRS complex.
      Greater complexity arises in arrhythmia patients, since V(MHD) varies between
      sinus-rhythm and arrhythmic beats. The 3DQRS method uses a kernel consisting of 6
      electrocardiogram (ECG) precordial leads (V1-V6), compiled from a 12-lead ECG
      performed outside the magnet. The kernel is cross-correlated with signals
      acquired inside the MRI to identify the QRS complex in real time. The 3DQRS
      method was evaluated against a vectorcardiogram (VCG)-based approach in two
      premature ventricular contraction (PVC) and two atrial fibrillation (AF)
      patients, a healthy exercising athlete, and eight healthy volunteers, within 1.5T
      and 3T MRIs, using a prototype MRI-conditional 12-lead ECG system. Two volunteers
      were recorded at 7T using a Holter recorder. RESULTS: For QRS complex detection,
      3DQRS subject-averaged sensitivity levels, relative to VCG were: 1.5T (100%
      versus 96.7%), 3T (98.9% versus 92.2%), and 7T (96.2% versus 77.7%). CONCLUSION:
      The 3DQRS method was shown to be more effective in cardiac gating than a
      conventional VCG-based method.

PMID- 24453117
TI  - A double-imprinted diffraction-grating sensor based on a virus-responsive super
      aptamer hydrogel derived from an impure extract.
AB  - The detection of viruses is of interest for a number of fields including
      biomedicine, environmental science, and biosecurity. Of particular interest are
      methods that do not require expensive equipment or trained personnel, especially
      if the results can be read by the naked eye. A new "double imprinting" method was
      developed whereby a virus-bioimprinted hydrogel is further micromolded into a
      diffraction grating sensor by using imprint-lithography techniques to give a
      "Molecularly Imprinted Polymer Gel Laser Diffraction Sensor" (MIP-GLaDiS). A
      simple laser transmission apparatus was used to measure diffraction, and the
      system can read by the naked eye to detect the Apple Stem Pitting Virus (ASPV) at
      concentrations as low as 10 ng mL(-1), thus setting the limit of detection of
      these hydrogels as low as other antigen-binding methods such as ELISA or
      fluorescence-tag systems.

PMID- 24453118
TI  - Body-weight perception and related preoccupations in a large national sample of
      adolescents.
AB  - OBJECTIVES: This study aimed to investigate the association between body-weight
      (BW) perception, weight preoccupation and behaviour, including weight control
      practices and compulsive over-eating episodes, across gender and actual BW
      classes. DESIGN: This study used a cross-sectional observational study.
      PARTICIPANTS: A large, nationally representative sample of 6404 ninth-grade
      French adolescents was randomly selected from schools throughout France. METHODS:
      Weight and height were measured, and BW preoccupation, BW control practices and
      compulsive over-eating were self-reported using standardized questionnaires.
      RESULTS: Nearly one-third of adolescents misperceived their BW. Misperception was
      more frequent among girls than boys (42.2% vs. 27.3%, P < 0.01). Underestimation
      of BW among overweight adolescents, like BW overestimation among underweight
      adolescents, was associated with less preoccupation with weight and fewer weight
      control practices than accurate perception of BW. Normal weight adolescents who
      overestimated their BW were more likely to declare weight preoccupations (ORa =
      8.66 [6.67-11.25]), dieting (ORa = 4.81 [3.68-6.27]) and recurrent compulsive
      over-eating episodes (ORa = 2.36 [1.72-3.23]) compared with their counterparts
      who correctly estimated their BW. CONCLUSION: Our study underlines the role of
      these associations in each category of actual BW (underweight, normal weight and
      overweight) in a large national sample.

PMID- 24453119
TI  - First highly efficient and photostable E and C derivatives of 4,4-difluoro-4-bora
      3a,4a-diaza-s-indacene (BODIPY) as dye lasers in the liquid phase, thin films,
      and solid-state rods.
AB  - A new library of E- and C-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)
      derivatives has been synthesized through a straightforward protocol from
      commercially available BODIPY complexes, and a systematic study of the
      photophysical properties and laser behavior related to the electronic properties
      of the B-substituent group (alkynyl, cyano, vinyl, aryl, and alkyl) has been
      carried out. The replacement of fluorine atoms by electron-withdrawing groups
      enhances the fluorescence response of the dye, whereas electron-donor groups
      diminish the fluorescence efficiency. As a consequence, these compounds exhibit
      enhanced laser action with respect to their parent dyes, both in liquid solution
      and in the solid phase, with lasing efficiencies under transversal pumping up to
      73 % in liquid solution and 53 % in a solid matrix. The new dyes also showed
      enhanced photostability. In a solid matrix, the derivative of commercial dye
      PM597 that incorporated cyano groups at the boron center exhibited a very high
      lasing stability, with the laser emission remaining at the initial level after
      100 000 pump pulses in the same position of the sample at a 10 Hz repetition
      rate. Distributed feedback laser emission was demonstrated with organic films
      that incorporated parent dye PM597 and its cyano derivative. The films were
      deposited onto quartz substrates engraved with appropriate periodical structures.
      The C derivative exhibited a laser threshold lower than that of the parent dye as
      well as lasing intensities up to three orders of magnitude higher. 

PMID- 24453120
TI  - Establishing the resting state default mode network derived from functional
      magnetic resonance imaging tasks as an endophenotype: A twins study.
AB  - The resting state default mode network (DMN) has been shown to characterize a
      number of neurological and psychiatric disorders. Evidence suggests an underlying
      genetic basis for this network and hence could serve as potential endophenotype
      for these disorders. Heritability is a defining criterion for endophenotypes. The
      DMN is measured either using a resting-state functional magnetic resonance
      imaging (fMRI) scan or by extracting resting state activity from task-based fMRI.
      The current study is the first to evaluate heritability of this task-derived
      resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same
      sex twin pairs) completed five cognitive and emotion processing fMRI tasks.
      Resting state DMN functional connectivity was derived from these five fMRI tasks.
      We validated this approach by comparing connectivity estimates from task-derived
      resting activity for all five fMRI tasks, with those obtained using a dedicated
      task-free resting state scan in an independent cohort of 27 healthy individuals.
      Structural equation modeling using the classic twin design was used to estimate
      the genetic and environmental contributions to variance for the resting-state DMN
      functional connectivity. About 9-41% of the variance in functional connectivity
      between the DMN nodes was attributed to genetic contribution with the greatest
      heritability found for functional connectivity between the posterior cingulate
      and right inferior parietal nodes (P<0.001). Our data provide new evidence that
      functional connectivity measures from the intrinsic DMN derived from task-based
      fMRI datasets are under genetic control and have the potential to serve as
      endophenotypes for genetically predisposed psychiatric and neurological
      disorders.

PMID- 24453121
TI  - Squamous cell carcinoma of larynx in an 8-year-old child: successful management
      with chemo-radiation.
AB  - Incidence of laryngeal squamous cell cancer (SCC) in childhood is rare, more so
      in children below 10 years of age. Due to the rarity of the disease and
      nonspecific symptoms diagnosis often gets delayed. Treatment is challenging and
      demands expert multi-modality care. We describe the clinico-pathologic findings
      and management of laryngeal cancer with chemo-radiation in an 8-year-old male.
      After 18 months of completion of treatment the child is in complete remission
      clinically and radiologically. This report aims at increasing awareness of head
      and neck SCC in paediatric population and also underscores the importance of
      multi-modality care in managing such cases.

PMID- 24453123
TI  - Electronic health record systems: risks and benefits.

PMID- 24453122
TI  - A photocleavable masked nuclear-receptor ligand enables temporal control of C.
      elegans development.
AB  - The development and lifespan of C. elegans are controlled by the nuclear hormone
      receptor DAF-12, an important model for the vertebrate vitamin D and liver X
      receptors. As with its mammalian homologues, DAF-12 function is regulated by bile
      acid-like steroidal ligands; however, tools for investigating their biosynthesis
      and function in vivo are lacking. A flexible synthesis for DAF-12 ligands and
      masked ligand derivatives that enable precise temporal control of DAF-12 function
      was developed. For ligand masking, photocleavable amides of 5-methoxy-N-methyl-2
      nitroaniline (MMNA) were introduced. MMNA-masked ligands are bioavailable and
      after incorporation into the worm, brief UV irradiation can be used to trigger
      the expression of DAF-12 target genes and initiate development from dauer larvae
      into adults. The in vivo release of DAF-12 ligands and other small-molecule
      signals by using photocleavable MMNA-masked ligands will enable functional
      studies with precise spatial and temporal resolution. 

PMID- 24453125
TI  - Transcriptional profiling of recall responses to Francisella live vaccine strain.
AB  - Global gene expression profile changes were monitored in human peripheral blood
      mononuclear cells (PBMCs) after challenge with the live vaccine strain (LVS) of
      Francisella tularensis. Because these PBMCs were from individuals previously
      immunized with LVS, stimulating these cells with LVS should activate memory
      responses. The Ingenuity Pathway Analysis tool identified pathways, functions,
      and networks associated with this in vitro recall response, including novel
      pathways triggered by the memory response. Dendritic cell (DC) maturation was the
      most significant among the more than 25 relevant pathways discovered. Interleukin
      15, granulocyte-macrophage colony-stimulating factor, and triggering receptor
      expressed on myeloid cells 1 signaling pathways were also significant. Pathway
      analysis indicated that Class 1 antigen presentation may not be optimal with LVS
      vaccination. The top three biological functions were antigen presentation, cell
      mediated and humoral immune responses. Network analysis revealed that the top
      network associated with these functions had IFNgamma and TNFalpha in central
      interactive positions. Our results suggest that DC maturation is a key factor in
      the recall responses and that more effective antigen processing and presentation
      is needed for cytotoxic T lymphocyte responses. Taken together, these
      considerations are critical for future tularemia vaccine development studies. 

PMID- 24453124
TI  - Palladium-catalyzed difluoroalkylation of aryl boronic acids: a new method for
      the synthesis of aryldifluoromethylated phosphonates and carboxylic acid
      derivatives.
AB  - The palladium-catalyzed difluoroalkylation of aryl boronic acids with
      bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has
      been developed. This method provides a facile and useful access to a series of
      functionalized difluoromethylated arenes (ArCF2 PO(OEt)2 , ArCF2 CO2 Et, and
      ArCF2 CONR(1) R(2) ) that have important applications in drug discovery and
      development. Preliminary mechanistic studies reveal that a single electron
      transfer (SET) pathway may be involved in the catalytic cycle. 

PMID- 24453126
TI  - Copper-promoted oxidative coupling of enamides and alkynes for the synthesis of
      substituted pyrroles.
AB  - An efficient copper-promoted oxidative coupling of enamides with alkynes has been
      developed for the synthesis of substituted pyrroles. The reaction proceeded
      through C-H and N-H bond functionalization of enamides under mild conditions.

PMID- 24453127
TI  - Acculturation determines BMI percentile and noncore food intake in Hispanic
      children.
AB  - Hispanic children in the United States are disproportionately affected by
      obesity. The role of acculturation in obesity is unclear. This study examined the
      relation between child obesity, dietary intake, and maternal acculturation in
      Hispanic children. We hypothesized that children of more acculturated mothers
      would consume more unhealthy foods and would have higher body mass index (BMI)
      percentiles. A total of 209 Hispanic mothers of children aged 2-4 y (50% female,
      35.3 +/- 8.7 mo, BMI percentile: 73.1 +/- 27.8, 30% obese, 19% overweight) were
      recruited for an obesity prevention/reversal study. The associations between
      baseline maternal acculturation [Brief Acculturation Rating Scale for Mexican
      Americans-II (Brief ARSMA-II)], child BMI percentile, and child diet were
      examined. Factor analysis of the Brief ARSMA-II in Puerto Rican mothers resulted
      in 2 new factors, which were named the Hispanic Orientation Score (4 items,
      loadings: 0.64-0.81) and U.S. Mainland Orientation Score (6 items, loadings: 
      0.61-0.92). In the total sample, children who consumed more noncore foods were
      more likely to be overweight or obese (P < 0.01). Additionally, children of
      mothers with greater acculturation to the United States consumed more noncore
      foods (P < 0.0001) and had higher BMI percentiles (P < 0.04). However, mothers
      with greater Hispanic acculturation served fewer noncore foods (P < 0.0001). In
      the Puerto Rican subgroup of mothers, Puerto Rican mothers with greater
      acculturation to the United States served more noncore foods (P < 0.0001), but
      there was no association between acculturation and child BMI percentile in this
      subgroup. These mothers, however, served fewer sugar-sweetened beverages (P <
      0.01) compared with non-Puerto Rican mothers, and this may have negated the
      effect of noncore food consumption on BMI percentile. These data suggest a
      complex relation between acculturation, noncore food consumption, and child BMI
      percentile in Puerto Rican and non-Puerto Rican Hispanic children. 

PMID- 24453129
TI  - Stunting prevalence, plasma zinc concentrations, and dietary zinc intakes in a
      nationally representative sample suggest a high risk of zinc deficiency among
      women and young children in Cameroon.
AB  - Before initiating a mass zinc fortification program, this study assessed the
      prevalence of and risk factors for low zinc status among Cameroonian women and
      children. In a nationally representative survey, we randomly selected 30 clusters
      in each of 3 strata (North, South, and Yaounde/Douala) and 10 households per
      cluster, each with a woman aged 15-49 y and a child aged 12-59 mo (n = 1002
      households). Twenty-four-hour dietary recalls (with duplicates in a subset) and
      anthropometric measurements were conducted, and non-fasting blood was collected
      to measure plasma zinc concentration (PZC) and markers of inflammation. PZC was
      adjusted for methodologic factors (time of collection and processing, and
      presence of inflammation). The prevalence of stunting was 33% (32% South; 46%
      North; 13% Yaounde/Douala). Among women, 82% had low adjusted PZC (<50 MUg/dL for
      pregnant women; <66 MUg/dL for others; 79% South, 89% North, 76% Yaounde/Douala).
      Among children, 83% had low adjusted PZC (<65 MUg/dL; 80% South, 92% North, 74%
      Yaounde/Douala). Risk factors for low PZC among women and children and for low
      height-for-age Z-score among children were similar and included residence in the
      North region and rural areas and households with low socioeconomic status. Using
      estimated average requirement values from the International Zinc Nutrition
      Consultative Group (IZiNCG), 29 and 41% of women had inadequate zinc intakes,
      assuming moderate and low bioavailability, respectively, but only 8% of children
      had inadequate zinc intake. Depending on the estimated physiologic zinc
      requirement applied, 17% (IZiNCG) and 92% (Institute of Medicine) of women had
      inadequate absorbable zinc intakes. Total zinc intakes were greatest in the North
      region, possibly because of different dietary patterns in this area. Zinc
      deficiency is a public health problem among women and children in Cameroon,
      although PZC and dietary zinc yield different estimates of the prevalence of
      deficiency. Large-scale programs to improve zinc nutrition, including food
      fortification, are needed. 

PMID- 24453128
TI  - The Healthy Eating Index-2010 is a valid and reliable measure of diet quality
      according to the 2010 Dietary Guidelines for Americans.
AB  - The Healthy Eating Index (HEI), a measure of diet quality, was updated to reflect
      the 2010 Dietary Guidelines for Americans and the accompanying USDA Food
      Patterns. To assess the validity and reliability of the HEI-2010, exemplary menus
      were scored and 2 24-h dietary recalls from individuals aged >=2 y from the 2003
      2004 NHANES were used to estimate multivariate usual intake distributions and
      assess whether the HEI-2010 1) has a distribution wide enough to detect
      meaningful differences in diet quality among individuals, 2) distinguishes
      between groups with known differences in diet quality by using t tests, 3)
      measures diet quality independently of energy intake by using Pearson correlation
      coefficients, 4) has >1 underlying dimension by using principal components
      analysis (PCA), and 5) is internally consistent by calculating Cronbach's
      coefficient alpha. HEI-2010 scores were at or near the maximum levels for the
      exemplary menus. The distribution of scores among the population was wide (5th
      percentile = 31.7; 95th percentile = 70.4). As predicted, men's diet quality
      (mean HEI-2010 total score = 49.8) was poorer than women's (52.7), younger
      adults' diet quality (45.4) was poorer than older adults' (56.1), and smokers'
      diet quality (45.7) was poorer than nonsmokers' (53.3) (P < 0.01). Low
      correlations with energy were observed for HEI-2010 total and component scores
      (|r| <= 0.21). Cronbach's coefficient alpha was 0.68, supporting the reliability
      of the HEI-2010 total score as an indicator of overall diet quality. Nonetheless,
      PCA indicated multiple underlying dimensions, highlighting the fact that the
      component scores are equally as important as the total. A comparable reevaluation
      of the HEI-2005 yielded similar results. This study supports the validity and the
      reliability of both versions of the HEI. 

PMID- 24453130
TI  - Supplementation with calcium and short-chain fructo-oligosaccharides affects
      markers of bone turnover but not bone mineral density in postmenopausal women.
AB  - This 24-mo randomized, double-blind, controlled trial aimed to examine whether
      supplementation with a natural marine-derived multi-mineral supplement rich in
      calcium (Ca) taken alone and in conjunction with short-chain fructo
      oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD)
      and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non
      osteoporotic postmenopausal women were randomly assigned to daily supplements of
      800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin.
      BMD was measured before and after intervention along with BTMs, which were also
      measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in
      the Ca and CaFOS groups did not differ from that in the maltodextrin group.
      Secondary analysis of changes to BTMs over time identified a greater decline in
      osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared
      with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12
      mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group
      compared with the maltodextrin group. In exploratory subanalyses of each
      treatment group against the maltodextrin group, women classified with osteopenia
      and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P =
      0.03) BMD compared with the maltodextrin group, although this effect was
      restricted to those with higher total-body and mean spinal BMD at baseline,
      respectively. Although the change in BMD observed did not differ between the
      groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the
      maltodextrin group suggests a more favorable bone health profile after
      supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of
      total-body and spinal bone loss in postmenopausal women with osteopenia-an effect
      that warrants additional investigation. This trial was registered at
      www.controlled-trials.com as ISRCTN63118444. 

PMID- 24453131
TI  - Maternal dietary docosahexaenoic acid supplementation attenuates fetal growth
      restriction and enhances pulmonary function in a newborn mouse model of perinatal
      inflammation.
AB  - The preterm infant is often exposed to maternal and neonatal inflammatory stimuli
      and is born with immature lungs, resulting in a need for oxygen therapy.
      Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has
      been shown to attenuate inflammation in various human diseases. Previous studies
      demonstrated that maternal DHA supplementation during late gestation and
      lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present
      studies, we tested the hypothesis that DHA supplementation to the dam would
      reduce hyperoxic lung injury and growth deficits in a more severe model of
      systemic maternal inflammation, including lipopolysaccharide (LPS) and neonatal
      hyperoxia exposure. On embryonic day 16, dams were placed on DHA (6.3 g DHA/kg
      diet) or control diets and injected with saline or LPS. Diets were maintained
      through weaning. At birth, pups were placed in room air or hyperoxia for 14 d.
      Improvements in birth weight (P < 0.01), alveolarization (P <= 0.01), and
      pulmonary function (P <= 0.03) at 2 and 8 wk of age were observed in pups exposed
      to perinatal inflammation and born to DHA-supplemented dams compared with control
      diet-exposed pups. These improvements were associated with decreases in tissue
      macrophage numbers (P < 0.01), monocyte chemoattractant protein-1 expression (P
      <= 0.05), and decreases in soluble receptor for advanced glycation end products
      concentrations (P < 0.01) at 2 and 8 wk. Furthermore, DHA supplementation
      attenuated pulmonary fibrosis, which was associated with the reduction of matrix
      metalloproteinases 2, 3, and 8 (P <= 0.03) and collagen mRNA (P <= 0.05), and
      decreased collagen (P < 0.01) and vimentin (P <= 0.03) protein concentrations. In
      a model of severe inflammation, maternal DHA supplementation lessened
      inflammation and improved lung growth in the offspring. Maternal supplementation
      with DHA may be a therapeutic strategy to reduce neonatal inflammation. 

PMID- 24453133
TI  - Burden of diagnostic radiation exposure in children with sickle cell disease.
AB  - Children with sickle cell disease (SCD) are repeatedly exposed to diagnostic
      radiation. We identified 938 children with SCD who had 9,246 radiographic tests.
      Mean number of tests/patient was 9.9 (95% CI: 8.9-10.9) over 8,817 patient-years.
      Mean rate was 1.5 tests/year (95% CI: 1.3-1.6). On average, a child with SCD will
      have 26.7 (95% CI: 24.1-29.3) radiographic tests by 18 years of age, and 5% will
      have >=100 tests. Six percent have >=3 CT scans, which may be associated with an
      increased risk of cancer. Strong consideration should be given to limiting the
      exposure of children with SCD to radiation.

PMID- 24453134
TI  - The superacid HBr/AlBr(3) : protonation of benzene and ordered crystal structure
      of [C(6)H(7)](+)[Al(2)Br(7)](-).
AB  - Crystalline and properly ordered protonated benzene as the [C6 H7 ](+) [Al2 Br7
      ](-) ?(C6 H6 ) salt 1 are obtained by the combination of solid AlBr3 , benzene,
      and HBr gas. Compound 1 was characterized and verified by NMR, Raman and X-Ray
      spectroscopy. This unexpected simple and straight forward access shows that
      HBr/AlBr3 is an underestimated superacid that should be used more frequently. 

PMID- 24453135
TI  - Chemoselective polymerization control: from mixed-monomer feedstock to
      copolymers.
AB  - A novel chemoselective polymerization control yields predictable (co)polymer
      compositions from a mixture of monomers. Using a dizinc catalyst and a mixture of
      caprolactone, cyclohexene oxide, and carbon dioxide enables the selective
      preparation of either polyesters or polycarbonates or copoly(ester-carbonates).
      The selectivity depends on the nature of the zinc-oxygen functionality at the
      growing polymer chain end, and can be controlled by the addition of exogeneous
      switch reagents. 

PMID- 24453136
TI  - HPLC/UV analysis of polyacetylenes, phenylpropanoid and pyrrolidine alkaloids in
      medicinally used Codonopsis species.
AB  - INTRODUCTION: Codonopsis Radix is commonly used as a tonic in traditional Chinese
      medicine. However, there is no suitable method to assess the quality of
      Codonopsis Radix based on multiple components having potential bioactivities.
      OBJECTIVE: To establish a HPLC/UV method for simultaneous quantitation of
      polyacetylenes (lobetyol, lobetyolin, lobetyolinin, cordifolioidyne B),
      phenylpropanoid (tangshenoside I) and pyrrolidine alkaloids (codonopyrrolidiums
      A, B) in Codonopsis Radix. METHODS: Large-scale methanol extraction of Codonopsis
      Radix, followed by chromatographic separation, provided the seven analytes for
      quantitation standards. Ultrasound-assisted methanol extracts of samples were
      analysed using reversed phase, gradient elution HPLC monitored at 215 nm.
      RESULTS: The method developed allowed efficient separation of the seven compounds
      and the detection and quantitation limits of the seven analytes were 0.10-0.32
      ug/mL and 0.35-1.07 ug/mL, respectively. All calibration curves showed good
      linearities (r>0.9993) within the test ranges. Intraday and interday precisions
      were good with RSD<2.84%. The recoveries of all analytes ranged from 95.8 to
      104.7%. CONCLUSION: HPLC/UV is an efficient and accurate method of analysis for
      simultaneous quantitation of seven components in Codonopsis Radix.

PMID- 24453132
TI  - Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N
      = 725 surface-based Alzheimer's disease neuroimaging initiative study.
AB  - The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor
      for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD
      patients carrying the e4 allele compared to e4 noncarriers. Here we examined the
      effect of APOE e4 on hippocampal morphometry in a large imaging database-the
      Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented
      and constructed hippocampal surfaces from the baseline MR images of 725 subjects
      with known APOE genotype information including 167 with AD, 354 with mild
      cognitive impairment (MCI), and 204 normal controls. High-order correspondences
      between hippocampal surfaces were enforced across subjects with a novel inverse
      consistent surface fluid registration method. Multivariate statistics consisting
      of multivariate tensor-based morphometry (mTBM) and radial distance were computed
      for surface deformation analysis. Using Hotelling's T(2) test, we found
      significant morphological deformation in APOE e4 carriers relative to noncarriers
      in the entire cohort as well as in the nondemented (pooled MCI and control)
      subjects, affecting the left hippocampus more than the right, and this effect was
      more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent
      with previous studies that showed e4 carriers exhibit accelerated hippocampal
      atrophy; we extend these findings to a novel measure of hippocampal morphometry.
      Hippocampal morphometry has significant potential as an imaging biomarker of
      early stage AD.

PMID- 24453137
TI  - A functional MRI study of the relationship between naming treatment outcomes and
      resting state functional connectivity in post-stroke aphasia.
AB  - BACKGROUND: The majority of studies investigating the neural mechanisms
      underlying treatment in people with aphasia have examined task-based brain
      activity. However, the use of resting-state fMRI may provide another method of
      examining the brain mechanisms responsible for treatment-induced recovery, and
      allows for investigation into connectivity within complex functional networks
      METHODS: Eight people with aphasia underwent 12 treatment sessions that aimed to
      improve object naming. Half the sessions employed a phonologically-based task,
      and half the sessions employed a semantic-based task, with resting-state fMRI
      conducted pre- and post-treatment. Brain regions in which the amplitude of low
      frequency fluctuations (ALFF) correlated with treatment outcomes were used as
      seeds for functional connectivity (FC) analysis. FC maps were compared from pre-
      to post-treatment, as well as with a group of 12 healthy older controls RESULTS:
      Pre-treatment ALFF in the right middle temporal gyrus (MTG) correlated with
      greater outcomes for the phonological treatment, with a shift to the left MTG and
      supramarginal gyrus, as well as the right inferior frontal gyrus, post-treatment.
      When compared to controls, participants with aphasia showed both normalization
      and up-regulation of connectivity within language networks post-treatment,
      predominantly in the left hemisphere CONCLUSIONS: The results provide preliminary
      evidence that treatments for naming impairments affect the FC of language
      networks, and may aid in understanding the neural mechanisms underlying the
      rehabilitation of language post-stroke.

PMID- 24453138
TI  - Reelin gene variants and risk of autism spectrum disorders: an integrated meta
      analysis.
AB  - Autism spectrum disorder (ASD) is a severe neurological disorder with a high
      degree of heritability. Reelin gene (RELN), which plays a crucial role in the
      migration and positioning of neurons during brain development, has been strongly
      posed as a candidate gene for ASD. Genetic variants in RELN have been
      investigated as risk factors of ASD in numerous epidemiologic studies but with
      inconclusive results. To clearly discern the effects of RELN variants on ASD, the
      authors conducted a meta-analysis integrating case-control and transmission
      disequilibrium test (TDT) studies published through 2001 to 2013. Odds ratios
      (ORs) with 95% confidence intervals were used to estimate the associations
      between three RELN variants (rs736707, rs362691, and GGC repeat variant) and ASD.
      In overall meta-analysis, the summary ORs for rs736707, rs362691, and GGC repeat
      variant were 1.11 [95% confidence interval (CI): 0.80-1.54], 0.69 (95% CI: 0.56
      0.86), and 1.09 (95% CI: 0.97-1.23), respectively. Besides, positive result was
      also obtained in subgroup of broadly-defined ASD for rs362691 (OR = 0.67, 95% CI:
      0.52-0.86). Our meta-analysis revealed that the RELN rs362691, rather than
      rs736707 or GGC repeat variant, might contribute significantly to ASD risk.

PMID- 24453139
TI  - Sodium phosphaethynolate as a building block for heterocycles.
AB  - Phosphorus-containing heterocycles have evolved from laboratory curiosities to
      functional components, such as ligands in catalytically active metal complexes or
      molecular constituents in electronic devices. The straightforward synthesis of
      functionalized heterocycles on a larger scale remains a challenge. Herein, we
      report the use of the phosphaethynolate (OCP)(-) anion as a building block for
      various sterically unprotected and functionalized hydroxy substituted phosphorus
      heterocycles. Because the resulting heterocycles are themselves anions, they are
      building blocks in their own right and allow further facile functionalization.
      This property may be of interest in coordination chemistry and material science. 

PMID- 24453140
TI  - Electron transfer in a supramolecular associate of a fullerene fragment.
AB  - Herein, we investigate the association of a fullerene fragment, hemifullerene
      C30H12, with an electron-donating bowl-shaped tetrathiafulvalene derivative
      (truxTTF). UV/Vis titrations and DFT calculations support formation of the
      supramolecular complex, for which an association constant of log Ka = 3.6+/-0.3
      in CHCl3 at room temperature is calculated. Remarkably, electron transfer from
      truxTTF to C30H12 to form the fully charge-separated species takes place upon
      irradiation of the associate with light, constituting the first example in which
      a fullerene fragment mimics the electron-accepting behavior of fullerenes within
      a supramolecular complex.

PMID- 24453141
TI  - A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and
      choreoathetosis: part of the spectrum of brain-thyroid-lung syndrome.
AB  - The NKX2-1 (TTF-1 or TITF-1) gene on chromosome 14q13 codes for the thyroid
      transcription factor 1 (TTF-1). It is expressed in the developing brain, lung,
      and thyroid. Defects have been associated with chorea, hypothyroidism, and lung
      disease, comprising the "brain-thyroid-lung syndrome." We describe here 3 cases
      of novel missense mutation (c.626G>C; p.Arg209Pro) in NKX2-1 in 2 generations of
      a nonconsanguinous family. Firstly 2 sons were affected by childhood-onset
      hypothyroidism and a movement disorder characterized by ataxia in the early years
      followed by the emergence of a superimposed chorea. The mutation was also found
      in the granddaughter, when she presented with the same clinical features. We
      hypothesize that the mutation arose as a result of gonadal mosaicism, as the
      mutation was not detected in leucocyte DNA from either grandparent. The features
      are consistent with a diagnosis of Brain-thyroid-lung syndrome, which previously
      could have been classified as benign hereditary chorea with hypothyroidism. 

PMID- 24453142
TI  - Early surgical treatment in a case of myoclonus dystonia syndrome.
AB  - Myoclonus dystonia syndrome is often misdiagnosed in young children and
      appropriate treatment is delayed, which has a negative impact on motor
      development, participation, and emotional well-being. In severely affected
      patients, deep brain stimulation of the globus pallidus internus has been used
      successfully to treat both dystonia and myoclonus. Here, the authors present a
      case of early successful treatment of myoclonus dystonia syndrome by pallidal
      deep brain stimulation in a patient at the age of 17 years leading to 83%
      reduction in dystonia score and 89% reduction in myoclonus. The patient gained
      significant improvement in motor function as well as increased participation and
      reduced stigma. 

PMID- 24453144
TI  - Does infantile abduction deficit indicate duane retraction syndrome until
      disproven?
AB  - Duane retraction syndrome consists of abduction deficit and palpebral fissure
      narrowing, upshoots, or downshoots on adduction. Infants with abduction deficit
      should be considered to have Duane retraction syndrome until disproven, because
      congenital abducens nerve palsy is extremely rare. The abducens nerve on the
      affected side is absent in type 1 Duane retraction syndrome and in some type 3
      patients. The authors present a 7-month-old girl who showed limitation of
      abduction simulating Duane retraction syndrome. High-resolution magnetic
      resonance imaging (MRI) revealed atrophic lateral rectus and present abducens
      nerve. This report is important because this case showed that congenital abducens
      nerve palsy exists, although it is extremely rare, and high-resolution MRI could
      be pivotal for the differentiation of Duane retraction syndrome and congenital
      abducens nerve palsy in infancy. 

PMID- 24453143
TI  - Psychological and adjustment problems due to acquired brain lesions in pediatric
      patients: a comparison of vascular, infectious, and other origins.
AB  - The aim of this study was to describe psychological, behavioral, and adjustment
      problems in children and adolescents with acquired brain lesions of different
      origins. Three groups of patients with acquired brain lesions (15 patients with
      infectious origin, 37 with vascular origin, and 15 with other origin), ranging in
      age from 4 to 18 years, received a psychological evaluation, including the Child
      Behavior Checklist for ages 4 to 18 and the Vineland Adaptive Behavior Scale.
      About half of the total sample (47.8%) showed psychological problems.
      Difficulties varied according to the cause of the brain lesions. The most
      problematic patients were children with brain lesions of infectious origin,
      whereas children with brain lesions of vascular origin scored lower on most of
      the Child Behavior Checklist scales. The authors conclude that psychological and
      behavioral difficulties are very common among school-aged children with acquired
      brain lesions, and their relevance and impact must necessarily be considered. 

PMID- 24453145
TI  - Glutaric aciduria type II presenting as myopathy and rhabdomyolysis in a
      teenager.
AB  - Late-onset glutaric aciduria type II has been described recently as a rare but
      treatable cause of proximal myopathy in teenagers and adults. It is an autosomal
      recessive disease affecting fatty acid, amino acid, and choline metabolism. This
      is usually a result of 2 defective flavoproteins: either electron transfer
      flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase
      (ETF:QO). We present a 14-year-old boy with a background of autistic spectrum
      disorder who presented with severe muscle weakness and significant
      rhabdomyolysis. Before the onset of muscle weakness, he was very active but was
      completely bedridden at presentation. Diagnosis was established quickly by urine
      organic acid and plasma acylcarnitine analysis. He has shown significant
      improvement after starting oral riboflavin supplementation and is now fully
      mobile. This case highlights that late-onset glutaric aciduria type II is an
      important differential diagnosis to consider in teenagers presenting with
      proximal myopathy and rhabdomyolysis and it may not be associated with
      hypoglycemia. 

PMID- 24453146
TI  - Clobazam-clonazepam combination effective for stimulus-induced falling in
      hyperekplexia.
AB  - A child with the major form of hyperekplexia is presented who stopped ambulating
      because of frequent unexpected falls associated with acoustic and visual stimuli.
      A combination of clobazam and clonazepam was well tolerated and was rapidly and
      dramatically effective in eliminating the falls and restoring ambulation. 

PMID- 24453147
TI  - Behavioral Assessment of the Dysexecutive Syndrome for Children: an examination
      of clinical utility for children with attention-deficit hyperactivity disorder
      (ADHD).
AB  - The present study evaluated the utility of the Behavioral Assessment of
      Dysexecutive Syndrome for Children for discerning differences in executive
      functioning between attention-deficit hyperactivity disorder (ADHD) children and
      normal controls and examined its associations with real-life executive function
      as rated by parent reports on the Dysexecutive Questionnaire for Children. Sixty
      three children diagnosed with ADHD and 60 normal healthy peers were recruited for
      this study. All participants completed the Behavioral Assessment of Dysexecutive
      Syndrome for Children, while their parents completed the Dysexecutive
      Questionnaire for Children. Results revealed that the ADHD group exhibited
      significantly poorer performance than the controls on 3 subtests of the
      Behavioral Assessment of Dysexecutive Syndrome for Children (ie, Playing Cards
      Test, Water Test, and Zoo Map Test 2), as well as on the total Dysexecutive
      Questionnaire for Children. Significant correlation was found between the total
      Dysexecutive Questionnaire for Children and the 6-Part Test. Findings suggested
      that some subtests of the Behavioral Assessment of Dysexecutive Syndrome for
      Children were particularly useful for detecting real-life executive dysfunction
      in ADHD. Yet, further studies are needed to provide extended validity data. 

PMID- 24453148
TI  - Acute axonal polyneuropathy following honey-bee sting: a case report.
AB  - Hymenoptera stings lead to a myriad of neurologic manifestations by the mechanism
      of immediate or delayed hypersensitivity reactions. The more common form of
      polyneuropathy associated with these stings is the acute inflammatory
      demyelinating type. We describe a 6-year-old girl, who developed progressive,
      symmetrical, ascending weakness within 3 days after a bee sting. Serial nerve
      conduction studies confirmed acute, motor-predominant axonal polyneuropathy. Use
      of intravenous immunoglobulin induced halt of progression, prompt stabilization
      and a gradual recovery. This case highlights that even a single honey-bee sting
      can result in acute-onset axonal variety of polyneuropathy in children. 

PMID- 24453149
TI  - Relationship between common viral upper respiratory tract infections and febrile
      seizures in children from Suzhou, China.
AB  - This study aimed to determine the potential predisposing factors for the
      development of febrile seizures among children with upper respiratory tract
      infection in the eastern Chinese region. Participants were individuals aged 6
      months and 6 years (n = 189) who were diagnosed with febrile seizure, complicated
      with upper respiratory tract infection, and 174 age-matched children who had
      upper respiratory tract infection without seizures as controls. The viral
      antigens including influenza A and B, parainfluenza, adenovirus, and respiratory
      syncytial virus were detected from nasopharyngeal aspirates. The incidence of
      influenza A infection was much higher in patients with febrile seizure than
      controls, especially those children aged >36 months. Patients with influenza A
      infection had higher body temperatures at seizure occurrence, shorter seizure
      duration, and shorter fever duration before seizure onset. Influenza A infections
      are frequently associated with febrile seizure in children with upper respiratory
      tract infection. During an influenza epidemic, effective vaccination of children,
      especially those with a past history of febrile seizure, may minimize the
      development of febrile seizure. 

PMID- 24453150
TI  - Giant cerebral cysticercosis in an infant confused with a thalamic glioma.
AB  - Neurocysticercosis is a common parasitic infection of the central nervous system.
      Intraparenchymal giant cysticercosis has been described in literature, but this
      is a rare report of a thalamic giant cysticercosis in a young child where the
      diagnosis could be made on follow-up. A 11/2-year-old male child presented with
      seizures, hemiparesis, and features of raised intracranial pressure. Initial
      neuroimaging findings of thalamic swelling with minimal edema and contrast
      enhancement with choline peak on magnetic resonance spectroscopy were attributed
      to thalamic glioma. Subsequent imaging revealed a ring enhancing lesion with an
      eccentric nodule suggestive of neurocysticercosis. It later resolved with
      residual gliosis. The presence of a pathognomic scolex and the resolution of size
      and symptoms without definitive treatment helped in making the diagnosis. This
      report reinforces the importance of considering cysticercosis in diagnosis of
      acute presentations of large cerebral masses in infants, particularly in
      prevalent regions, and emphasizes the follow-up of these patients. 

PMID- 24453151
TI  - A new tool for identifying children with motor problems: reliability and validity
      study.
AB  - This study examined reliability and validity of the Zuk Assessment for diagnosis
      of motor problems and determined standardized scores in an Israeli population
      aged 5 to 6 years. For standardization, 156 children recruited from 13
      Kindergartens of typically developing children were evaluated with the Zuk
      Assessment. Intrarater and interrater reliability were examined on 2 samples of
      15 and 13 children, respectively. A total of 151 children referred for motor
      problems were examined with the Zuk and Movement Assessment Battery for Children
      assessment tools for validation of the Zuk Assessment. Findings showed that the
      Zuk total score had a normal distribution similar to that found in the literature
      identifying 5.1% (-2 standard deviations) and 12% (between -1 and -2 standard
      deviations) of children with motor-related problems. Reliability was indicated by
      high intraclass correlation scores both in intrarater (intraclass correlation =
      .89) and interrater (intraclass correlation = .95) paradigms. The Zuk assessment
      identified differences in subgroups, namely, typical, suspicious, and impaired,
      as found in the Movement Assessment Battery for Children, confirming the Zuk
      validity.

PMID- 24453152
TI  - Enterovirus 71 infection-associated acute flaccid paralysis: a case series of
      long-term neurologic follow-up.
AB  - The authors undertook long-term neurologic outcomes of 27 patients aged 0 to 15
      years with enterovirus 71-related acute flaccid paralysis from June 1998 to July
      2012. Motor function outcome was graded from class I (complete recovery) to class
      V (permanent paralytic limbs). Twelve of 20 patients (60%) who received
      intravenous immunoglobulin for treatment of acute flaccid paralysis had motor
      function outcomes in classes III to V. The median duration of follow-up was 6
      months, during which time 7 of 13 patients (54%) with central nervous system
      infection, 3 of 6 patients (50%) with autonomic nervous system dysregulation, and
      3 of 8 patients (37%) with heart failure showed motor function outcomes in
      classes III to V. These findings suggested that the usage of intravenous
      immunoglobulin and the severity of disease staging at disease onset might not be
      able to predict long-term motor function outcomes. 

PMID- 24453153
TI  - Evolutive leukoencephalopathy in congenital cytomegalovirus infection.
AB  - Congenital cytomegalovirus infection is the most common infectious cause of
      congenital brain injury. Type and severity of congenital cytomegalovirus
      infection-related brain abnormalities depend on the developmental stage of the
      central nervous system at the time of fetal infection. The aim of this study was
      to follow the course of leukoencephalopathy in a patient with congenital
      cytomegalovirus infection. We describe brain magnetic resonance imaging (MRI)
      findings of a boy with symptomatic congenital cytomegalovirus infection performed
      at the age of 3 weeks, 13 months, and 4 and 7 years. Neonatal brain MRI showed
      most of characteristic findings in congenital cytomegalovirus infection with most
      prominent white matter abnormalities and cortical dysplasia. MRI follow-up images
      showed that cortical dysgenesis remained unchanged and static, whereas white
      matter abnormalities evolved over the years. We propose that leukoencephalopathy
      in congenital cytomegalovirus infection is not only nonprogressive or static but
      even evolutive and suggests both underlying disruption and delay of myelination. 

PMID- 24453154
TI  - Stroke in a case of neonatal lupus: an uncommon complication.
AB  - Stroke is an extremely rare complication of congenital heart block in children.
      We report a 2-year-old girl with congenital complete heart block who presented
      with acute-onset right middle cerebral artery territory stroke. The congenital
      heart block was secondary to maternal lupus. 

PMID- 24453156
TI  - Vitamin B12 deficiency in children: a treatable cause of neurodevelopmental
      delay.
AB  - Vitamin B12 deficiency in children can rarely cause neurologic manifestations. In
      this series, 14 pediatric cases (median age 11 months) have been described in
      whom association of vitamin B12 deficiency with developmental delay or regression
      was observed. Severe to profound delay was present in 8 (57%) patients. All the
      patients were exclusively or predominantly breast-fed and 10 of 12 mothers had
      low serum vitamin B12 levels. Three to 6 months after treatment, a mean gain of
      development quotient of 38.8 points was seen in 7 follow-ups. In settings with a
      high prevalence of vitamin B12 deficiency, this association should be actively
      searched for. 

PMID- 24453155
TI  - Global developmental delay, progressive relapsing-remitting parkinsonism, and
      spinal syrinx in a child with SOX6 mutation.
AB  - SOX6, a member of the SOX gene family, plays a key role in the development of
      several mammalian tissues and organs, including the central nervous system.
      Specifically, this gene modulates the differentiation and proliferation of
      interneurons in the medial ganglionic eminence, as well as oligodendrocytes in
      the spinal cord. We describe the case of a 4-year-old girl with global
      developmental delay and a spinal cord syrinx who presented with recurrent
      episodes of parkinsonian symptoms subsequent to febrile illnesses. The symptoms
      included gait instability, tremor, and dysarthria, with a progressive relapsing
      remitting course over the span of 2 years. The patient was later found to have a
      large deletion-type mutation in the SOX6 gene. This case is the first report in
      humans implying a role for SOX6 in basal ganglia function, as well as spinal cord
      development. 

PMID- 24453157
TI  - The prognostic value of concurrent Horner syndrome in extended Erb obstetric
      brachial plexus palsy.
AB  - Horner syndrome may be seen in infants with extended Erb obstetric brachial
      plexus palsy. However, its prognostic value in these infants has not been
      previously investigated. A total of 220 infants with extended Erb palsy were
      included and divided into 2 groups: group I (n = 209) were infants with extended
      Erb palsy without Horner syndrome, and group II (n = 11) were infants with
      extended Erb palsy and concurrent Horner syndrome. The rate of good spontaneous
      recovery of elbow flexion was 59% in group I and 27% in group II, and the
      difference was significant (P = .038). The rate of good spontaneous recovery of
      wrist extension was 61% in group I and 0% in group II, and the difference as
      highly significant (P < .0001). Concurrent Horner syndrome in infants with
      extended Erb palsy may be considered as a poor prognostic sign for recovery of
      the sixth and seventh cervical roots. 

PMID- 24453158
TI  - Episodic epileptic verbal auditory agnosia in Landau Kleffner syndrome treated
      with combination diazepam and corticosteroids.
AB  - We report 2 pediatric patients who presented initially with seizures followed by
      subacute language regression characterized by a verbal auditory agnosia. These
      previously normal children had no evidence of expressive aphasia during their
      symptomatic periods. Further, in both cases, auditory agnosia was associated with
      sleep-activated electroencephalographic (EEG) epileptiform activity, consistent
      with Landau-Kleffner syndrome. However, both cases are unique since the episodic
      auditory agnosia and sleep-activated EEG epileptiform activity rapidly responded
      to combination therapy with pulse benzodiazepine and corticosteroids. Further, in
      each case, recurrences were characterized by similar symptoms, EEG findings, and
      beneficial responses to the pulse benzodiazepine and corticosteroid therapy.
      These observations suggest that pulse combination high-dose corticosteroid and
      benzodiazepine therapy may be especially effective in Landau-Kleffner syndrome. 

PMID- 24453159
TI  - 16p13.11 microdeletion in a patient with hemiconvulsion-hemiplegia-epilepsy
      syndrome: a case report.
AB  - We describe a patient with hemiconvulsion-hemiplegia-epilepsy syndrome. The
      pathophysiology of hemiconvulsion-hemiplegia-epilepsy syndrome remains uncertain
      and there are probably multiple potential contributing factors. Our patient had a
      chromosomal 16p13.11 microdeletion that confers susceptibility to various types
      of epilepsy. This is the first report detailing an association of hemiconvulsion
      hemiplegia-epilepsy syndrome with a 16p13.11 deletion and identifies another
      potential causal factor for hemiconvulsion-hemiplegia-epilepsy syndrome. 

PMID- 24453160
TI  - Development of novel mechanisms for housing, handling, and remote monitoring of
      common marmosets at animal biosafety level 3.
AB  - The use of common marmosets as an alternative non-human primate model for
      infectious disease research using BSL-3 viruses such as Rift Valley fever virus
      (RVFV) presents unique challenges with respect to housing, handling, and safety.
      Subject matter experts from veterinary care, animal husbandry, biosafety,
      engineering, and research were consulted to design a pilot experiment using
      marmosets infected with RVFV. This paper reviews the caging, handling, and safety
      related adaptations and modifications that were required to humanely utilize
      marmosets as a model for high-hazard BSL-3 viral diseases. 

PMID- 24453161
TI  - An easy, convenient cell and tissue extraction protocol for nuclear magnetic
      resonance metabolomics.
AB  - INTRODUCTION: As a complement to the classic metabolomics biofluid studies, the
      visualisation of the metabolites contained in cells or tissues could be a very
      powerful tool to understand how the local metabolism and biochemical pathways
      could be affected by external or internal stimuli or pathologies. Therefore,
      extraction and/or lysis is necessary to obtain samples adapted for use with the
      current analytical tools (liquid NMR and MS). These extraction or lysis work-ups
      are often the most labour-intensive and rate-limiting steps in metabolomics, as
      they require accuracy and repeatability as well as robustness. Many of the
      procedures described in the literature appear to be very time-consuming and not
      easily amenable to automation. OBJECTIVE: To find a fast, simplified procedure
      that allows release of the metabolites from cells and tissues in a way that is
      compatible with NMR analysis. METHODS: We assessed the use of sonication to
      disrupt cell membranes or tissue structures. Both a vibrating probe and an
      automated bath sonicator were explored. RESULTS: The application of sonication as
      the disruption procedure led to reproducible NMR spectral data compatible with
      metabolomics studies. This method requires only a small biological tissue or cell
      sample, and a rapid, reduced work-up was applied before analysis. The spectral
      patterns obtained are comparable with previous, well-described extraction
      protocols. CONCLUSION: The rapidity and the simplicity of this approach could
      represent a suitable alternative to the other protocols. Additionally, this
      approach could be favourable for high- throughput applications in intracellular
      and intratissular metabolite measurements.

PMID- 24453162
TI  - Progression of brain atrophy in the early stages of Parkinson's disease: a
      longitudinal tensor-based morphometry study in de novo patients without cognitive
      impairment.
AB  - The presence of brain atrophy and its progression in early Parkinson's disease
      (PD) are still a matter of debate, particularly in patients without cognitive
      impairment. The aim of this longitudinal study was to assess whether PD patients
      who remain cognitively intact develop progressive atrophic changes in the early
      stages of the disease. For this purpose, we employed high-resolution T1-weighted
      MR imaging to compare 22 drug-naive de novo PD patients without cognitive
      impairment to 17 age-matched control subjects, both at baseline and at three-year
      follow-up. We used tensor-based morphometry to explore the presence of atrophic
      changes at baseline and to compute yearly atrophy rates, after which we performed
      voxel-wise group comparisons using threshold-free cluster enhancement. At
      baseline, we did not observe significant differences in regional atrophy in PD
      patients with respect to control subjects. In contrast, PD patients showed
      significantly higher yearly atrophy rates in the prefrontal cortex, anterior
      cingulum, caudate nucleus, and thalamus when compared to control subjects. Our
      results indicate that even cognitively preserved PD patients show progressive
      cortical and subcortical atrophic changes in regions related to cognitive
      functions and that these changes are already detectable in the early stages of
      the disease.

PMID- 24453163
TI  - A generic tool for transcription factor target gene discovery in Arabidopsis cell
      suspension cultures based on tandem chromatin affinity purification.
AB  - Genome-wide identification of transcription factor (TF) binding sites is pivotal
      to our understanding of gene expression regulation. Although much progress has
      been made in the determination of potential binding regions of proteins by
      chromatin immunoprecipitation, this method has some inherent limitations
      regarding DNA enrichment efficiency and antibody necessity. Here, we report an
      alternative strategy for assaying in vivo TF-DNA binding in Arabidopsis
      (Arabidopsis thaliana) cells by tandem chromatin affinity purification (TChAP).
      Evaluation of TChAP using the E2Fa TF and comparison with traditional chromatin
      immunoprecipitation and single chromatin affinity purification illustrates the
      suitability of TChAP and provides a resource for exploring the E2Fa
      transcriptional network. Integration with transcriptome, cis-regulatory element,
      functional enrichment, and coexpression network analyses demonstrates the quality
      of the E2Fa TChAP sequencing data and validates the identification of new direct
      E2Fa targets. TChAP enhances both TF target mapping throughput, by circumventing
      issues related to antibody availability, and output, by improving DNA enrichment
      efficiency. 

PMID- 24453165
TI  - Simultaneous quantification of L-tetrahydropalmatine and its urine metabolites by
      ultra high performance liquid chromatography with tandem mass spectrometry.
AB  - l-tetrahydropalmatine (l-THP) is a tetrahydroprotoberberine isoquinoline alkaloid
      that has been used as an analgesic agent in China for more than 40 years. Recent
      studies indicated its potential application in the treatment of drug addiction.
      In this study, a sensitive and rapid method using ultra high performance liquid
      chromatography with MS/MS was developed and validated for simultaneous
      quantitation of l-THP and its desmethyl metabolites. Enzymatic hydrolysis was
      integrated into sample preparation to enable the quantitative determination of
      both free and conjugated metabolites. Chromatographic separation was achieved on
      an Agilent Poroshell 120 EC-C18 column. Detection was performed by MS in the
      positive ion ESI mode. The calibration curves of the analytes were linear (r(2) >
      0.9936) over the concentration range of 1-1000 ng/mL with the lower limit of
      quantification at 1 ng/mL. The precision for both intra- and interday
      determinations was <8.97%, and the accuracy ranged from -8.74 to 8.65%. The
      recovery for all the analytes was >70% without significant matrix effect. The
      method has been successfully applied to the urinary excretion study of l-THP in
      rats. The conjugates were found to be the major urine metabolites of the drug. 

PMID- 24453166
TI  - S-F and S-C activation of SF6 and SF5 derivatives at rhodium: conversion of SF6
      into H2S.
AB  - The degradation of SF6 and SF5 organyls by S-F and S-C bond-activation reactions
      at [{Rh(MU-H)(dippp)}2] under mild conditions is reported. Fluorido and thiolato
      species were identified as products or intermediates, and were characterized by X
      ray diffraction analysis and multinuclear NMR spectroscopy. An unprecedented
      cyclic process for the conversion of the potent greenhouse gas SF6 into H2S was
      developed.

PMID- 24453164
TI  - Plastidial NAD-dependent malate dehydrogenase is critical for embryo development
      and heterotrophic metabolism in Arabidopsis.
AB  - In illuminated chloroplasts, one mechanism involved in reduction-oxidation
      (redox) homeostasis is the malate-oxaloacetate (OAA) shuttle. Excess electrons
      from photosynthetic electron transport in the form of nicotinamide adenine
      dinucleotide phosphate, reduced are used by NADP-dependent malate dehydrogenase
      (MDH) to reduce OAA to malate, thus regenerating the electron acceptor NADP. NADP
      MDH is a strictly redox-regulated, light-activated enzyme that is inactive in the
      dark. In the dark or in nonphotosynthetic tissues, the malate-OAA shuttle was
      proposed to be mediated by the constitutively active plastidial NAD-specific MDH
      isoform (pdNAD-MDH), but evidence is scarce. Here, we reveal the critical role of
      pdNAD-MDH in Arabidopsis (Arabidopsis thaliana) plants. A pdnad-mdh null mutation
      is embryo lethal. Plants with reduced pdNAD-MDH levels by means of artificial
      microRNA (miR-mdh-1) are viable, but dark metabolism is altered as reflected by
      increased nighttime malate, starch, and glutathione levels and a reduced
      respiration rate. In addition, miR-mdh-1 plants exhibit strong pleiotropic
      effects, including dwarfism, reductions in chlorophyll levels, photosynthetic
      rate, and daytime carbohydrate levels, and disordered chloroplast ultrastructure,
      particularly in developing leaves, compared with the wild type. pdNAD-MDH
      deficiency in miR-mdh-1 can be functionally complemented by expression of a
      microRNA-insensitive pdNAD-MDH but not NADP-MDH, confirming distinct roles for
      NAD- and NADP-linked redox homeostasis. 

PMID- 24453167
TI  - Building nanocomposite magnets by coating a hard magnetic core with a soft
      magnetic shell.
AB  - Controlling exchange coupling between hard magnetic and soft magnetic phases is
      the key to the fabrication of advanced magnets with tunable magnetism and high
      energy density. Using FePt as an example, control over the magnetism in exchange
      coupled nanocomposites of hard magnetic face-centered tetragonal (fct) FePt and
      soft magnetic Co (or Ni, Fe2C) is shown. The dispersible hard magnetic fct-FePt
      nanoparticles are first prepared with their coercivity (Hc) reaching 33 kOe. Then
      core/shell fct-FePt/Co (or Ni, Fe2C) nanoparticles are synthesized by reductive
      thermal decomposition of the proper metal precursors in the presence of fct-FePt
      nanoparticles. These core/shell nanoparticles are strongly coupled by exchange
      interactions and their magnetic properties can be rationally tuned by the shell
      thickness of the soft phase. This work provides an ideal model system for the
      study of exchange coupling at the nanoscale, which will be essential for building
      superstrong magnets for various permanent magnet applications in the future.

PMID- 24453168
TI  - Anti-biofilm agents: recent breakthrough against multi-drug resistant
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a Gram-positive pathogen that causes potentially life
      threatening nosocomial- and community-acquired infections, such as osteomyelitis
      and endocarditis. Staphylococcus aureus has the ability to form multicellular,
      surface-adherent communities called biofilms, which enables it to survive in
      various sources of stress, including antibiotics, nutrient limitations, heat
      shock, and immune responses. Biofilm-forming capacity is now recognized as an
      important virulence determinant in the development of staphylococcal device
      related infections. In light of the projected increase in the numbers of elderly
      patients who will require semi-permanent indwelling medical devices such as
      artificial knees and hips, we can anticipate an expanded need for new agents and
      treatment options to manage biofilm-associated infections in an expanding at-risk
      population. With better understanding of staphylococcal biofilm formation and
      growth, novel strategies that target biofilm-associated infections caused by S.
      aureus have recently been described and seem promising as future anti-biofilm
      therapies.

PMID- 24453169
TI  - Rapid separation of free fatty acids in vegetable oils by capillary zone
      electrophoresis.
AB  - INTRODUCTION: Olive oil is a very important product to human health since it
      inhibits formation of free radicals, tumour growth, lesions and inflammatory
      substances. High concentrations of free fatty acids in olive oils results in
      lipid deterioration due to oxidative or hydrolytic rancidity. OBJECTIVE: To
      optimise an alternative capillary zone electrophoresis methodology, under
      ultraviolet indirect detection and to determine free fatty acids in edible
      vegetable oils without derivatisation steps in sample preparation. METHODS: The
      condition used consisted of 15 mm NaH2 PO4 -Na2 HPO4 at pH ~6.86, 4.0 mm of
      sodium dodecybenzenesulphonate, 8.3 mm of Brij 35(r), 45% v/v of acetonitrile and
      2.1% of 1-octanol, injection at 12.0 mbar of pressure for 4 s, +19 kV of applied
      voltage and indirect detection at 224 nm, within an analysis time of 11 min.
      RESULTS: The capillary zone electrophoresis method was successfully applied to
      determination of free fatty acids in extra virgin olive oil, virgin olive oil and
      soybean oil samples. The comparison with the official volumetric titration method
      showed no significant difference within the 95% confidence interval. CONCLUSION:
      The main advantage to the proposed method is the possibility to observe the
      individual amount of the free fatty acids, which would be useful for researchers
      interested in studying the effect of the free fatty acids profile on oxidative
      process in food.

PMID- 24453170
TI  - Aging effects on the resting state motor network and interlimb coordination.
AB  - Both increases and decreases in resting state functional connectivity have been
      previously observed within the motor network during aging. Moreover, the
      relationship between altered functional connectivity and age-related declines in
      bimanual coordination remains unclear. Here, we explored the developmental
      dynamics of the resting brain within a task-specific motor network in a sample of
      128 healthy participants, aged 18-80 years. We found that age-related increases
      in functional connectivity between interhemispheric dorsal and ventral premotor
      areas were associated with poorer performance on a novel bimanual visuomotor
      task. Additionally, a control analysis performed on the default mode network
      confirmed that our age-related increases in functional connectivity were specific
      to the motor system. Our findings suggest that increases in functional
      connectivity within the resting state motor network with aging reflect a loss of
      functional specialization that may not only occur in the active brain but also in
      the resting brain.

PMID- 24453171
TI  - Chemoselective catalytic conjugate addition of alcohols over amines.
AB  - A highly chemoselective conjugate addition of alcohols in the presence of amines
      is described. The cooperative nature of the catalyst enabled chemoselective
      activation of alcohols over amines, allowing the conjugate addition to soft Lewis
      basic alpha,beta-unsaturated nitriles. Divergent transformation of the nitrile
      functionality highlights the utility of the present catalysis. 

PMID- 24453172
TI  - Selective extraction of berberine from Cortex Phellodendri using polydopamine
      coated magnetic nanoparticles.
AB  - A new extraction agent featuring dopamine self-polymerized on magnetic Fe3 O4
      nanoparticles has been successfully synthesized and evaluated for the SPE of
      berberine from the extract of the traditional Chinese medicinal plant, Cortex
      Phellodendri. The nanoparticles prepared possessed a core-shell structure and
      showed super-paramagnetism. It was found that these polydopamine-coated
      nanoparticles exhibited strong and selective adsorption for berberine. Among the
      chemical components present in C. Phellodendri, only berberine was adsorbed by
      the nanoparticles and extracted by a following SPE procedure. Various conditions
      such as the amount of polydopamine-coated nanoparticles, desorption solvent,
      desorption time and equilibrium time were optimized for the SPE of berberine. The
      purity of berberine extracted from C. Phellodendri was determined to be as high
      as 91.3% compared with that of 9.5% in the extract. The established SPE protocol
      combined advantages of highly selective enrichment with easy magnetic separation,
      and proved to be a facile efficient procedure for the isolation of berberine.
      Further, the prepared polydopamine-coated magnetic nanoparticles could be reused
      for multiple times, reducing operational cost. The applicability and reliability
      of the developed SPE method were demonstrated by isolating berberine from three
      different C. Phellodendri extracts. Recoveries of 85.4-111.2% were obtained with
      relative standard deviations ranging from 0.27-2.05%. 

PMID- 24453173
TI  - Gallium oxide nanorods: novel, template-free synthesis and high catalytic
      activity in epoxidation reactions.
AB  - Gallium oxide nanorods with unprecedented small dimensions (20-80 nm length and 3
      5 nm width) were prepared using a novel, template-free synthesis method. This
      nanomaterial is an excellent heterogeneous catalyst for the sustainable
      epoxidation of alkenes with H2 O2 , rivaling the industrial benchmark microporous
      titanosilicate TS-1 with linear alkenes and being much superior with bulkier
      substrates. A thorough characterization study elucidated the correlation between
      the physicochemical properties of the gallium oxide nanorods and their catalytic
      performance, and underlined the importance of the nanorod morphology for
      generating a material with high specific surface area and a high number of
      accessible acid sites. 

PMID- 24453174
TI  - Mycobacterium tuberculosis pellicles express unique proteins recognized by the
      host humoral response.
AB  - Mycobacterium tuberculosis (MTB) causes both acute and chronic infections in
      humans characterized by tolerance to antibiotics and reactivation to cause
      secondary tuberculosis. These characteristics have led to renewed interest in the
      in vitro pellicle, or biofilm mode of growth, where bacteria grow to produce a
      thick aggregate at the air-liquid interface and exhibit increased phenotypic
      resistance to antibiotics. We infected guinea pigs with the virulent H37Rv strain
      of MTB for 60 days at which point we collected blood. To identify antigenic
      proteins, membrane protein extracts of MTB H37Ra pellicles and shaken cultures
      grown for 3, 5, or 7 weeks were probed with the infected animals' sera after the
      proteins were separated by two-dimensional gel electrophoresis (2DGE). Antigenic
      proteins were then identified using MALDI-TOF/TOF mass spectrometry peptide mass
      fingerprinting. Antigenic pellicle proteins were compared across the three
      timepoints to identify those that were produced consistently during pellicle
      growth. They were also compared to those membrane proteins identified from
      harvested shaken cultures to determine pellicle-specific vs. universally
      expressed proteins. Using this technique, we identified 44 distinct antigenic
      proteins, nine of which were pellicle-specific. The sequence of antigenic
      pellicle-specific proteins was checked for sequence conservation across 15
      sequenced MTB clinical isolates, three other members of the MTB complex, as well
      as M. avium and M. smegmatis. The antigenic pellicle-specific protein Rv0097 was
      found to have very high sequence conservation within the MTB complex but not with
      related mycobacteria, while FabG4 was highly conserved in all mycobacteria
      analyzed. These conserved pellicle-specific proteins represent targets for the
      development of future diagnostic tests and vaccines.

PMID- 24453175
TI  - Sensitive and selective determination of phenolic compounds from aromatic plants
      using an electrochemical detection coupled with HPLC method.
AB  - INTRODUCTION: Phenolic compounds contained in essential oils from plants are
      responsible for their anti-oxidant capacity. The natural extract from each
      aromatic plant is characterised by a typical ratio of phenolic components, so
      each one of the essential oils shows different properties. OBJECTIVE: The
      development of a simple reversed-phase high-performance liquid chromatographic
      (RP-HPLC) method for the determination of phenolic compounds from aromatic plants
      using spectrophotometric detection with a diode-array and electrochemical
      detection with amperometric and coulometric detectors. METHODS: Chromatographic
      conditions are optimised to separate vanillin, eugenol, thymol and carvacrol
      using spectrophotometric detection. Acetonitrile and methanol are studied as
      mobile-phase organic modifiers. The hydrodynamic curves are obtained for both
      electrochemical detection modes and the principal values of merit are calculated.
      The proposed methodology is applied to determine the four analytes in real
      samples. RESULTS: The shortest elution times and the highest electrochemical
      signals are achieved using 65% methanol solution in 0.1 mol/L acetic acid-acetate
      buffer as the mobile phase. Potential values of 0.925 V for amperometric
      detection and 0.500 V for coulometric detection are chosen as working potentials.
      The limits of detection (LOD) for the compounds studied ranged between 9.7-17
      ug/L and 0.81-3.1 ug/L in amperometric and coulometric detection modes,
      respectively. In general, the obtained LODs are better than those previously
      reported. CONCLUSION: The low LODs obtained using coulometric detection make this
      methodology very competitive and adequate for quality control of these phenolic
      compounds in comparison with others, such as GC-MS, that are more expensive and
      complicated to use than the RP-HPLC method with coulometric detection.

PMID- 24453176
TI  - Common and dissociated mechanisms for estimating large and small dot arrays:
      value-specific fMRI adaptation.
AB  - An fMRI pair-adaptation paradigm was used to identify the brain regions linked to
      the apprehension of small and large numbers of items. Participants classified
      stimuli on the basis of their numerosities (fewer or more than five dots). We
      manipulated the type of repetition within pairs of dot arrays. Overall processing
      of pairs with small as opposed to large quantities was associated with a
      decreased BOLD response in the midline structures and inferior parietal cortex.
      The opposite pattern was observed in middle cingulate cortex. Pairs in which the
      same numerosity category was repeated, were associated with a decreased signal in
      the left prefrontal and the left inferior parietal cortices, compared with when
      numerosities changed. Repetitions of exact numerosities irrespective of sample
      size were associated with decreased responses in bi-lateral prefrontal, sensory
      motor regions, posterior occipital and left intraparietal sulcus (IPS). More
      importantly, we found value-specific adaptation specific to repeated small
      quantity in the left lateral occipito-temporal cortex, irrespective of whether
      the exact same stimulus pattern repeated. Our results indicate that a large
      network of regions (including the IPS) support visual quantity processing
      independent of the number of items present; however assimilation of small
      quantities is associated with additional support from regions within the left
      occipito-temporal cortex. We propose that processing of small quantities is aided
      by a subitizing-specific network. This network may account for the increased
      processing efficiency often reported for numerosities in the subitizing range.

PMID- 24453177
TI  - Enantioselective organocatalytic oxaziridination of N-tosyl aldimine catalyzed by
      Cinchona alkaloid-ester derivatives.
AB  - A series of cinchona alkaloid-ester derivatives was synthesized and applied to
      catalyze the enantioselective oxaziridination of aryl aldimines with m-CPBA. The
      (R,R)-oxaziridines were obtained in good yields with high enantiomeric excess
      (ee) values (up to 98%).

PMID- 24453179
TI  - Inhibitory effects of PLAP-1/asporin on periodontal ligament cells.
AB  - PLAP-1/asporin is an extracellular matrix protein that is predominantly expressed
      in the human periodontal ligament (PDL) and has an aspartic acid (D) repeat
      polymorphism in its N-terminal region. In this study, we hypothesized that the D
      repeat polymorphism of PLAP-1/asporin may affect the physiological functions of
      periodontal ligaments. We established periodontal ligament cell lines transfected
      with the D13- or D14-PLAP-1 gene. Alkaline phosphatase staining and alizarin red
      staining revealed that the cytodifferentiation of the D14-PLAP-1-expressing PDL
      cells was more repressed compared with that of the D13-PLAP-1-expressing cells.
      Furthermore, the D14-PLAP-1-expressing cells inhibited BMP-2-induced
      cytodifferentiation more strongly than did the D13-PLAP-1-expressing cells.
      Western blotting analysis and luciferase assay revealed that D14-PLAP-1
      suppressed BMP-2 signal transduction more efficiently than did D13-PLAP-1, and co
      immunoprecipitation demonstrated the stronger affinity of the D14-PLAP-1 protein
      to BMP-2 compared with the D13-PLAP-1 protein. Analysis of these data suggests
      that the D repeat polymorphism of PLAP-1/asporin has a significant influence on
      the functions of PDL cells. 

PMID- 24453180
TI  - Ascorbic acid as an initiator for the direct C-H arylation of (hetero)arenes with
      anilines nitrosated in situ.
AB  - Ascorbic acid (vitamin C) has been used as a radical initiator in a metal-free
      direct C-H arylation of (hetero)arenes. Starting from an aniline, the
      corresponding arenediazonium ion is generated in situ and immediately reduced by
      vitamin C to an aryl radical that undergoes a homolytic aromatic substitution
      with a (hetero)arene. Notably, neither heating nor irradiation is required. This
      procedure is mild, operationally simple, and constitutes a greener approach to
      arylation.

PMID- 24453181
TI  - Helical carbon and graphite films prepared from helical poly(3,4
      ethylenedioxythiophene) films synthesized by electrochemical polymerization in
      chiral nematic liquid crystals.
AB  - Helical carbon and graphite films from helical poly(3,4-ethylenedioxythiophene)
      (H-PEDOT) films synthesized through electrochemical polymerization in a chiral
      nematic liquid-crystal (N*-LC) field are prepared. The microscope investigations
      showed that the H-PEDOT film synthesized in the N*-LC has large domains of one
      handed spiral morphology consisting of fibril bundles. The H-PEDOT films
      exhibited distinct Cotton effects in circular dichroism spectra. The highly
      twisted N*-LC with a helical pitch of smaller than 1 MUm produced the H-PEDOT
      film with a highly ordered morphology. The spiral morphologies with left- and
      right-handed screws were observed for the carbon films prepared from the H-PEDOT
      films at 800  degrees C and were well correlated with the textures and helical
      pitches of the N*-LCs. The spiral morphologies of the precursors were also
      retained even in the graphite films prepared from the helical carbon films at
      2600  degrees C. 

PMID- 24453178
TI  - TMJ degeneration in SAMP8 mice is accompanied by deranged Ihh signaling.
AB  - The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint
      during mastication, and its continuous use and stress can lead to degeneration
      over age. Using senescence-accelerated (SAMP8) mice that develop early
      osteoarthritis-like changes in synovial joints at high frequency, we analyzed
      possible molecular mechanisms of TMJ degeneration and tested whether and how
      malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice
      displayed early-onset osteoarthritic changes that included reductions in
      superficial/chondroprogenitor cell number, proteoglycan/collagen content, and
      Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by
      tooth milling, the SAMP8 condyles became morphologically defective, displayed
      even lower proteoglycan levels, and underwent abnormal chondrocyte maturation
      compared with malocclusion-treated condyles in wild-type mice. Malocclusion also
      induced faster progression of pathologic changes with increasing age in SAMP8
      condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors
      and increased TUNEL-positive apoptotic cells. These changes were accompanied by
      steeper reductions in Ihh signaling and by expression of matrix metalloproteinase
      13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show
      for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied
      by--and possibly attributable to--altered Ihh signaling and that occlusal
      dysfunction accelerates progression toward degenerative TMJ disease in this
      model.

PMID- 24453183
TI  - Tandem solid-phase extraction followed by HPLC-ESI/QTOF/MS/MS for rapid screening
      and structural identification of trace diterpenoids in flowers of Rhododendron
      molle.
AB  - INTRODUCTION: 'Naoyanghua', composed of the flowers of Rhododendron molle G. Don,
      is a traditional Chinese medicine that is widely known for its toxicity.
      Grayanane-type diterpenoids are the main active ingredients in R. molle, as well
      as possibly their toxicity: they are, however, difficult to isolate and analyse
      using common chromatographic methods, due to their small amounts and absence of
      conjugated groups, such as phenyl and alpha, beta-unsaturated ketone. OBJECTIVE:
      To establish a highly sensitive, selective and reliable method for the
      qualitative evaluation of trace diterpenoids in the flowers of R. molle by using
      tandem solid-phase extraction followed by high-performance liquid chromatography
      with electrospray ionisation quadrupole-time-of-flight mass spectrometry (HPLC
      ESI/QTOF/MS/MS). METHODS: Tandem solid phase extraction (SPE) was undertaken
      using a polyamide cartridge and a C18E cartridge in succession to enrich the
      trace diterpenoids. HPLC-ESI/QTOF/MS/MS was used to determine the fragmentation
      patterns of diterpenoids and to tentatively characterise their fragmentation
      pathways. RESULTS: HPLC-ESI/QTOF/MS/MS detected a total of 14 diterpenoids, eight
      of which were identified by comparison with literature sources and six based on
      fragmentation analysis. Among the latter six, rhodojaponin VI-3-glucoside was
      tentatively identified as a new diterpenoid glycoside and rhodojaponin VII,
      rhodojaponin IV and rhodojaponin I were reported from R. molle for the first
      time. CONCLUSION: By qualitative research of diterpenoids in this plant by HPLC
      ESI/QTOF/MS/MS, a reliable methodology for the analysis of these active
      constituents of R. molle was established for the first time.

PMID- 24453182
TI  - Electrospun PGS:PCL microfibers align human valvular interstitial cells and
      provide tunable scaffold anisotropy.
AB  - Tissue engineered heart valves (TEHV) can be useful in the repair of congenital
      or acquired valvular diseases due to their potential for growth and remodeling.
      The development of biomimetic scaffolds is a major challenge in heart valve
      tissue engineering. One of the most important structural characteristics of
      mature heart valve leaflets is their intrinsic anisotropy, which is derived from
      the microstructure of aligned collagen fibers in the extracellular matrix (ECM).
      In the present study, a directional electrospinning technique is used to
      fabricate fibrous poly(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds
      containing aligned fibers, which resemble native heart valve leaflet ECM
      networks. In addition, the anisotropic mechanical characteristics of fabricated
      scaffolds are tuned by changing the ratio of PGS:PCL to mimic the native heart
      valve's mechanical properties. Primary human valvular interstitial cells (VICs)
      attach and align along the anisotropic axes of all PGS:PCL scaffolds with various
      mechanical properties. The cells are also biochemically active in producing heart
      valve-associated collagen, vimentin, and smooth muscle actin as determined by
      gene expression. The fibrous PGS:PCL scaffolds seeded with human VICs mimick the
      structure and mechanical properties of native valve leaflet tissues and would
      potentially be suitable for the replacement of heart valves in diverse patient
      populations. 

PMID- 24453184
TI  - Dissociable identity- and modality-specific neural representations as revealed by
      cross-modal nonspatial inhibition of return.
AB  - There are ongoing debates on whether object concepts are coded as supramodal
      identity-based or modality-specific representations in the human brain. In this
      fMRI study, we adopted a cross-modal "prime-neutral cue-target" semantic priming
      paradigm, in which the prime-target relationship was manipulated along both the
      identity and the modality dimensions. The prime and the target could refer to
      either the same or different semantic identities, and could be delivered via
      either the same or different sensory modalities. By calculating the main effects
      and interactions of this 2 (identity cue validity: "Identity_Cued" vs.
      "Identity_Uncued") * 2 (modality cue validity: "Modality_Cued" vs.
      "Modality_Uncued") factorial design, we aimed at dissociating three neural
      networks involved in creating novel identity-specific representations independent
      of sensory modality, in creating modality-specific representations independent of
      semantic identity, and in evaluating changes of an object along both the identity
      and the modality dimensions, respectively. Our results suggested that bilateral
      lateral occipital cortex was involved in creating a new supramodal semantic
      representation irrespective of the input modality, left dorsal premotor cortex,
      and left intraparietal sulcus were involved in creating a new modality-specific
      representation irrespective of its semantic identity, and bilateral superior
      temporal sulcus was involved in creating a representation when the identity and
      modality properties were both cued or both uncued. In addition, right inferior
      frontal gyrus showed enhanced neural activity only when both the identity and the
      modality of the target were new, indicating its functional role in novelty
      detection.

PMID- 24453185
TI  - Neighboring residue effects in terminally blocked dipeptides: implications for
      residual secondary structures in intrinsically unfolded/disordered proteins.
AB  - For nuclear magnetic resonance (NMR)-based protein structure determinations, the
      random coil chemical shifts are very important because the secondary and tertiary
      protein structure predictions become possible by examining deviations of measured
      chemical shifts from those reference chemical shift values. In addition,
      neighboring residue effects on chemical shifts and J-coupling constants are
      crucial in understanding the nature of conformational propensities exhibited by
      unfolded or intrinsically disordered proteins. We recently reported the 1D NMR
      results for a complete set of terminally blocked dipeptides (Oh KI, Jung YS,
      Hwang GS, Cho M. J Biomol NMR 2012;53:25-41), but the NMR resonance assignments
      were not possible so that the average chemical shifts and J-coupling constants
      were only considered. In the present work, to thoroughly investigate the
      neighboring residue effects and random coil chemical shifts we extend the
      previous studies with 2D NMR, and measured all the (3) J(HNHalpha) values and
      H(alpha) and H(N) chemical shifts of the same set of terminally blocked
      dipeptides that are free from structural effects like secondary structure,
      hydrogen-bond, long-range backbone, and side-chain interactions. In particular,
      the preceding and following residue effects on amino-acid backbone conformational
      propensities are revealed and directly compared with previous works on either
      short peptides or empirical chemical shift database.

PMID- 24453186
TI  - Iron(II)-catalyzed direct cyanation of arenes with aryl(cyano)iodonium triflates.
AB  - A direct oxidative cyanation of arenes under Fe(II) catalysis with 3,5
      di(trifluoromethyl)phenyl(cyano)iodonium triflate (DFCT) as the cyanating agent
      has been developed. The reaction is applicable to wide range of aromatic
      substrates, including polycyclic structures and heteroaromatic compounds. 

PMID- 24453188
TI  - The jmzQuantML programming interface and validator for the mzQuantML data
      standard.
AB  - The mzQuantML standard from the HUPO Proteomics Standards Initiative has recently
      been released, capturing quantitative data about peptides and proteins, following
      analysis of MS data. We present a Java application programming interface (API)
      for mzQuantML called jmzQuantML. The API provides robust bridges between Java
      classes and elements in mzQuantML files and allows random access to any part of
      the file. The API provides read and write capabilities, and is designed to be
      embedded in other software packages, enabling mzQuantML support to be added to
      proteomics software tools (http://code.google.com/p/jmzquantml/). The mzQuantML
      standard is designed around a multilevel validation system to ensure that files
      are structurally and semantically correct for different proteomics quantitative
      techniques. In this article, we also describe a Java software tool
      (http://code.google.com/p/mzquantml-validator/) for validating mzQuantML files,
      which is a formal part of the data standard. 

PMID- 24453187
TI  - Single mutations in tau modulate the populations of fibril conformers through
      seed selection.
AB  - Seeded conversion of tau monomers into fibrils is a central step in the
      progression of tau pathology in Alzheimer's disease and other neurodegenerative
      disorders. Self-assembly is mediated by the microtubule binding repeats in tau.
      There are either three or four repeats present depending on the protein isoform.
      Here, double electron-electron resonance spectroscopy was used to investigate the
      conformational ensemble of four-repeat tau fibrils. Single point mutations at key
      positions in the protein (DeltaK280, P301S, P312I, D314I) markedly change the
      distribution of fibril conformers after template-assisted growth, whereas other
      mutations in the protein (I308M, S320F, G323I, G326I, Q336R) do not. These
      findings provide unprecedented insights into the seed selection of tau disease
      mutants and establish conformational compatibility as an important driving force
      in tau fibril propagation. 

PMID- 24453189
TI  - Chemometric resolution approaches in characterisation of volatile constituents in
      Plantago ovata seeds using gas chromatography-mass spectrometry: methodology and
      performance assessment.
AB  - INTRODUCTION: Comprehensive chemical profiling of herbal medicines (HMs) is a
      major challenge in chemical characterisation of source materials. Many analytical
      platforms such as gas chromatography-mass spectrometry (GC-MS) have been applied
      to the characterisation. However, the great complexity of analytical results has
      been an obstacle. Chemometric resolution methods as a supplementary tool for data
      processing are proposed for solving this problem. OBJECTIVE: To develop and
      demonstrate the ability of chemometric techniques in the characterisation of
      volatile components in herbal medicines. METHODS: The volatile components of
      Plantago ovata were extracted using a solvent extraction method. GC-MS analysis
      were performed using an Agilent HP-6890 gas chromatograph equipped with a HP-5MS
      capillary, interfaced with an Agilent HP- 5973 mass selective detector. Resolved
      spectra were identified by matching against the standard mass spectral database
      of the National Institute of Standards and Technology (NIST). RESULTS: Results of
      this study show that the 71 constituents that are qualitatively recognised
      represent 94.53% of the total relative content of constituents from Plantago
      ovata oil, whereas without applying the chemometric methods only 51 constituents
      were recognised by direct searching utilising a mass database. In addition the
      presence of valuable components such as thymol, 2,4-decadienal, linoleic acid and
      oleic acid in Plantago ovata oil has been demonstrated. CONCLUSION: GC-MS
      combined with chemometric resolution methods, such as multivariate curve
      resolution-alternating least squares (MCR-ALS), will provide a reliable means for
      rapid and accurate analyses of unknown complicated practical systems.

PMID- 24453190
TI  - Prediction of human actions: expertise and task-related effects on neural
      activation of the action observation network.
AB  - The action observation network (AON) is supposed to play a crucial role when
      athletes anticipate the effect of others' actions in sports such as tennis. We
      used functional magnetic resonance imaging to explore whether motor expertise
      leads to a differential activation pattern within the AON during effect
      anticipation and whether spatial and motor anticipation tasks are associated with
      a differential activation pattern within the AON depending on participant
      expertise level. Expert (N=16) and novice (N=16) tennis players observed video
      clips depicting forehand strokes with the instruction to either indicate the
      predicted direction of ball flight (spatial anticipation) or to decide on an
      appropriate response to the observed action (motor anticipation). The experts
      performed better than novices on both tennis anticipation tasks, with the experts
      showing stronger neural activation in areas of the AON, namely, the superior
      parietal lobe, the intraparietal sulcus, the inferior frontal gyrus, and the
      cerebellum. When novices were contrasted with experts, motor anticipation
      resulted in stronger activation of the ventral premotor cortex, the supplementary
      motor area, and the superior parietal lobe than spatial anticipation task did. In
      experts, the comparison of motor and spatial anticipation revealed no increased
      activation. We suggest that the stronger activation of areas in the AON during
      the anticipation of action effects in experts reflects their use of the more fine
      tuned motor representations they have acquired and improved during years of
      training. Furthermore, results suggest that the neural processing of different
      anticipation tasks depends on the expertise level.

PMID- 24453192
TI  - Synthesis of triangular tripalladium cations as noble-metal analogues of the
      cyclopropenyl cation.
AB  - The first C3 -symmetric 44-core-valence-electron triangular palladium clusters,
      [{(SAr')(PAr3 )Pd}3 ](+) , have been synthesized by activation of the C?S bond of
      isothioureas. Owing to delocalized metal-metal bonding, these stable complexes
      are the first noble-metal analogues of the pi-aromatic cyclopropenyl cation [C3
      H3 ](+) , with their all-metal aromaticity involving d-type atomic orbitals. 

PMID- 24453191
TI  - Consumption of acidic water alters the gut microbiome and decreases the risk of
      diabetes in NOD mice.
AB  - Infant formula and breastfeeding are environmental factors that influence the
      incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To
      determine if altering the intestinal microbiome is one mechanism through which an
      acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt
      mice on neutral (N) or acidified H2O and monitored the impact on microbial
      composition and diabetes incidence. NOD-N mice showed an increased development of
      diabetes, while exhibiting a decrease in Firmicutes and an increase in
      Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of
      age. NOD-N mice had a decrease in the levels of Foxp3 expression in
      CD4(+)Foxp3(+) cells, as well as decreased CD4(+)IL17(+) cells, and a lower ratio
      of IL17/IFNgamma CD4+ T-cells. Our data clearly indicates that a change in the
      acidity of liquids consumed dramatically alters the intestinal microbiome, the
      presence of protective Th17 and Treg cells, and the incidence of diabetes. This
      data suggests that early dietary manipulation of intestinal microbiota may be a
      novel mechanism to delay T1D onset in genetically pre-disposed individuals. 

PMID- 24453193
TI  - Highly efficient near-infrared organic light-emitting diode based on a butterfly
      shaped donor-acceptor chromophore with strong solid-state fluorescence and a
      large proportion of radiative excitons.
AB  - The development of near-infrared (NIR) organic light-emitting diodes (OLEDs) is
      of growing interest. Donor-acceptor (D-A) chromophores have served as an
      important class of NIR materials for NIR OLED applications. However, the external
      quantum efficiencies (EQEs) of NIR OLEDs based on conventional D-A chromophores
      are typically below 1 %. Reported herein is a butterfly-shaped D-A compound, PTZ
      BZP. A PTZ-BZP film displayed strong NIR fluorescence with an emission peak at
      700 nm, and the corresponding quantum efficiency reached 16 %. Remarkably, the
      EQE of the NIR OLED based on PTZ-BZP was 1.54 %, and a low efficiency roll-off
      was observed, as well as a high radiative exciton ratio of 48 %, which breaks
      through the limit of 25 % in conventional fluorescent OLEDs. Experimental and
      theoretical investigations were carried out to understand the excited-state
      properties of PTZ-BZP. 

PMID- 24453195
TI  - Enantiomeric separation of underivatized amino acids: predictability of chiral
      recognition on ristocetin a chiral stationary phase.
AB  - The present work aimed to investigate the predictability of the chromatographic
      behavior for the separation of underivatized amino acids on ristocetin A, known
      as Chirobiotic R, using a DryLab high-performance liquid chromatography (HPLC)
      method development software, which is typically used to predict the effect of
      changing various chromatographic parameters on resolution in the reversed phase
      mode. After implementing the basic runs, and judging the predictability via the
      computed resolution map, it can be deduced that the chiral recognition mechanisms
      tend towards a hydrophilic interaction chromatography rather than the reversed
      phase mode, which limits the ability of DryLab software to predict separations on
      Chirobiotic R.

PMID- 24453194
TI  - The utilization of fluorescence to identify the components of lipofuscin by
      imaging mass spectrometry.
AB  - Lipofuscin, an aging marker in the retinal pigment epithelium (RPE) associated
      with the development of age-related macular degeneration, is primarily
      characterized by its fluorescence. The most abundant component of RPE lipofuscin
      is N-retinylidene-N-retinylethanolamine (A2E) but its exact composition is not
      known due to the complexity of the RPE extract. In this study, we utilized MALDI
      imaging to find potential molecules responsible for lipofuscin fluorescence in
      RPE tissue from Abca4(-/-) , Sv129, and C57Bl6/J mice aged 2 and 6 months. To
      assert relationships, the individual images in the MALDI imaging datasets were
      correlated with lipofuscin fluorescence recorded from the same tissues following
      proper registration. Spatial correlation information, which is usually lost in
      bioanalytics, pinpointed a relatively small number of potential lipofuscin
      components. The comparison of four samples in each condition further limited the
      possibility of false positives and provided various new, age- and strain-specific
      targets. Validating the usefulness of the fluorescence-enhanced imaging strategy,
      many known adducts of A2E were identified in the short list of lipofuscin
      components. These results provided evidence that mass spectrometric imaging can
      be utilized as a tool to begin to identify the molecular substructure of
      clinically-relevant diagnostic information. 

PMID- 24453206
TI  - A B-C double bond unit coordinated to platinum: an alkylideneboryl ligand that is
      isoelectronic to neutral aminoborylene Ligands.
AB  - The reaction of [Pt(PCy3)2] with Br2B-CH(SiMe3)2 resulted in generation of the
      first alkylideneboryl complex, trans-[Br(Cy3P)2Pt{B=CH(SiMe3)}], with concomitant
      elimination of Me3 SiBr. The trans bromide ligand of the alkylideneboryl complex
      was readily substituted by a methyl group upon treatment with methyllithium,
      leading to another alkylideneboryl complex, trans-[Me(Cy3P)2Pt{B=CH(SiMe3)}].
      Various spectrochemical techniques, single-crystal X-ray crystallography, and
      quantum chemical calculations confirmed the formulation of a double bond between
      the boron and the carbon atom. The theoretical studies also provided evidence for
      the stronger trans influence of the alkylideneboryl ligand over iminoboryl and
      oxoboryl ligands.

PMID- 24453207
TI  - Solvent-driven chiral-interaction reversion for organogel formation.
AB  - For chiral gels and related applications, one of the critical issues is how to
      modulate the stereoselective interaction between the gel and the chiral guest
      precisely, as well as how to translate this information into the macroscopic
      properties of materials. Herein, we report that this process can also be
      modulated by nonchiral solvents, which can induce a chiral-interaction reversion
      for organogel formation. This process could be observed through the clear
      difference in gelation speed and the morphology of the resulting self-assembly.
      This chiral effect was successfully applied in the selective separation of
      quinine enantiomers and imparts "smart" merits to the gel materials. 

PMID- 24453208
TI  - Proteomic profiles of human lung adeno and squamous cell carcinoma using super
      SILAC and label-free quantification approaches.
AB  - Nonsmall cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is
      subdivided into two major histological subtypes: adenocarcinoma (ADC) and
      squamous cell carcinoma (SCC). There is an unmet need to further subdivide NSCLC
      according to distinctive molecular features that may be associated with
      responsiveness to therapies. Four primary tumor-derived xenograft proteomes (two
      each ADC and SCC) were quantitatively compared by using a super-SILAC labeling
      approach together with ultrahigh-resolution MS. Proteins highly differentially
      expressed in the two subtypes were identified, including 30 that were validated
      in an independent cohort of 12 NSCLC primary tumor-derived xenograft tumors whose
      proteomes were quantified by an alternative, label-free shotgun MS methodology.
      The 30-protein signature contains metabolism enzymes including phosphoglycerate
      dehydrogenase, which is more highly expressed in SCC, as well as a comprehensive
      set of cytokeratins and other components of the epithelial barrier, which is
      therefore distinctly different between ADC and SCC. These results demonstrate the
      utility of the super-SILAC method for the characterization of primary tissues,
      and compatibility with datasets derived from different MS-based platforms. The
      validation of proteome signatures of NSCLC subtypes supports the further
      development and application of MS-based quantitative proteomics as a basis for
      precision classifications and treatments of tumors. All MS data have been
      deposited in the ProteomeXchange with identifier PXD000438
      (http://proteomecentral.proteomexchange.org/dataset/PXD000438). 

PMID- 24453210
TI  - Enantiomerically pure [M(6)L(12)] or [M(12)L(24)] polyhedra from flexible
      bis(pyridine) ligands.
AB  - Coordination-driven self-assembly is one of the most powerful strategies to
      prepare nanometer-sized discrete (supra)molecular assemblies. Herein, we report
      on the use of two constitutionally isomeric BINOL-based bis(pyridine) ligands for
      this purpose. Upon coordination to Pd(II) ions these self-assemble into
      enantiomerically pure endo- and exo-functionalized hexa- and dodecanuclear
      metallosupramolecular spheres with a chiral skeleton depending on the
      substitution pattern of the BINOL core. These aggregates were characterized by
      NMR, MS, DLS, TEM, and EELS as well as ECD. Furthermore, experimental ECD data
      could be compared to those obtained from theoretical simulations using a
      simplified Tamm-Dancoff approximation to time-dependent DFT to rationalize the
      extraordinary high molar circular dichroisms. Despite the rotational freedom
      around the central aryl-aryl bond of these ligands, the self-assembly process
      happens completely selective in a "narcissistic" self-recognition manner. 

PMID- 24453211
TI  - Quantitative phosphoproteomic analysis of RIP3-dependent protein phosphorylation
      in the course of TNF-induced necroptosis.
AB  - Tumor necrosis factor (TNF) induced cell death in murine fibrosarcoma L929 cells
      is a model system in studying programed necrosis (also known as necroptosis).
      Receptor interacting protein 3 (RIP3), a serine-threonine kinase, is known to
      play an essential role in TNF-induced necroptosis; however, the phosphorylation
      events initiated by RIP3 activation in necroptotic process is still largely
      unknown. Here, we performed a quantitative MS based analysis to compare TNF
      induced changes in the global phosphoproteome of wild-type (RIP3(+/+) ) and RIP3
      knockdown L929 cells at different time points after TNF treatment. A total of
      8058 phosphopeptides spanning 6892 phosphorylation sites in 2762 proteins were
      identified in the three experiments, in which cells were treated with TNF for
      0.5, 2, and 4 h. By comparing the phosphorylation sites in wild-type and RIP3
      knockdown L929 cells, 174, 167, and 177 distinct phosphorylation sites were
      revealed to be dependent on RIP3 at the 0.5, 2, and 4 h time points after TNF
      treatment, respectively. Notably, most of them were not detected in a previous
      phosphoproteomic analysis of RIP3-dependent phosphorylation in lipopolysaccharide
      stimulated peritoneal macrophages and TNF-treated murine embryonic fibroblasts
      (MEFs), suggesting that the data presented in this report are highly relevant to
      the study of TNF-induced necroptosis of L929 cells. 

PMID- 24453212
TI  - The double-stranded transcriptome of Escherichia coli.
AB  - Advances in high-throughput transcriptome analyses have revealed hundreds of
      antisense RNAs (asRNAs) for many bacteria, although few have been characterized,
      and the number of functional asRNAs remains unknown. We have developed a genome
      wide high-throughput method to identify functional asRNAs in vivo. Most
      mechanisms of gene regulation via asRNAs require an RNA-RNA interaction with its
      target RNA, and we hypothesized that a functional asRNA would be found in a
      double strand (dsRNA), duplexed with its cognate RNA in a single cell. We
      developed a method of isolating dsRNAs from total RNA by immunoprecipitation with
      a ds-RNA specific antibody. Total RNA and immunoprecipitated dsRNA from
      Escherichia coli RNase III WT and mutant strains were deep-sequenced. A
      statistical model was applied to filter for biologically relevant dsRNA regions,
      which were subsequently categorized by location relative to annotated genes. A
      total of 316 potentially functional asRNAs were identified in the RNase III
      mutant strain and are encoded primarily opposite to the 5' ends of transcripts,
      but are also found opposite ncRNAs, gene junctions, and the 3' ends. A total of
      21 sense/antisense RNA pairs identified in dsRNAs were confirmed by Northern blot
      analyses. Most of the RNA steady-state levels were higher or detectable only in
      the RNase III mutant strain. Taken together, our data indicate that a significant
      amount of dsRNA is formed in the cell, that RNase III degrades or processes these
      dsRNAs, and that dsRNA plays a major role in gene regulation in E. coli. 

PMID- 24453214
TI  - Probing large conformational rearrangements in wild-type and mutant spectrin
      using structural mass spectrometry.
AB  - Conformational changes of macromolecular complexes play key mechanistic roles in
      many biological processes, but large, highly flexible proteins and protein
      complexes usually cannot be analyzed by crystallography or NMR. Here, structures
      and conformational changes of the highly flexible, dynamic red cell spectrin and
      effects of a common mutation that disrupts red cell membranes were elucidated
      using chemical cross-linking coupled with mass spectrometry. Interconversion of
      spectrin between closed dimers, open dimers, and tetramers plays a key role in
      maintaining red cell shape and membrane integrity, and spectrins in other cell
      types serve these as well as more diverse functions. Using a minispectrin
      construct, experimentally verified structures of closed dimers and tetramers were
      determined by combining distance constraints from zero-length cross-links with
      molecular models and biophysical data. Subsequent biophysical and structural mass
      spectrometry characterization of a common hereditary elliptocytosis-related
      mutation of alpha-spectrin, L207P, showed that cell membranes were destabilized
      by a shift of the dimer-tetramer equilibrium toward closed dimers. The structure
      of alphaL207P mutant closed dimers provided previously unidentified mechanistic
      insight into how this mutation, which is located a large distance from the
      tetramerization site, destabilizes spectrin tetramers and cell membrane
      integrity. 

PMID- 24453213
TI  - Sel1L is indispensable for mammalian endoplasmic reticulum-associated
      degradation, endoplasmic reticulum homeostasis, and survival.
AB  - Suppressor/Enhancer of Lin-12-like (Sel1L) is an adaptor protein for the E3
      ligase hydroxymethylglutaryl reductase degradation protein 1 (Hrd1) involved in
      endoplasmic reticulum-associated degradation (ERAD). Sel1L's physiological
      importance in mammalian ERAD, however, remains to be established. Here, using the
      inducible Sel1L knockout mouse and cell models, we show that Sel1L is
      indispensable for Hrd1 stability, ER homeostasis, and survival. Acute loss of
      Sel1L leads to premature death in adult mice within 3 wk with profound pancreatic
      atrophy. Contrary to current belief, our data show that mammalian Sel1L is
      required for Hrd1 stability and ERAD function both in vitro and in vivo. Sel1L
      deficiency disturbs ER homeostasis, activates ER stress, attenuates translation,
      and promotes cell death. Serendipitously, using a biochemical approach coupled
      with mass spectrometry, we found that Sel1L deficiency causes the aggregation of
      both small and large ribosomal subunits. Thus, Sel1L is an indispensable
      component of the mammalian Hrd1 ERAD complex and ER homeostasis, which is
      essential for protein translation, pancreatic function, and cellular and
      organismal survival. 

PMID- 24453215
TI  - Structure of signaling-competent neurotensin receptor 1 obtained by directed
      evolution in Escherichia coli.
AB  - Crystallography has advanced our understanding of G protein-coupled receptors,
      but low expression levels and instability in solution have limited structural
      insights to very few selected members of this large protein family. Using
      neurotensin receptor 1 (NTR1) as a proof of principle, we show that two directed
      evolution technologies that we recently developed have the potential to overcome
      these problems. We purified three neurotensin-bound NTR1 variants from
      Escherichia coli and determined their X-ray structures at up to 2.75 A resolution
      using vapor diffusion crystallization experiments. A crystallized construct was
      pharmacologically characterized and exhibited ligand-dependent signaling,
      internalization, and wild-type-like agonist and antagonist affinities. Our
      structures are fully consistent with all biochemically defined ligand-contacting
      residues, and they represent an inactive NTR1 state at the cytosolic side. They
      exhibit significant differences to a previously determined NTR1 structure
      (Protein Data Bank ID code 4GRV) in the ligand-binding pocket and by the presence
      of the amphipathic helix 8. A comparison of helix 8 stability determinants
      between NTR1 and other crystallized G protein-coupled receptors suggests that the
      occupancy of the canonical position of the amphipathic helix is reduced to
      various extents in many receptors, and we have elucidated the sequence
      determinants for a stable helix 8. Our analysis also provides a structural
      rationale for the long-known effects of C-terminal palmitoylation reactions on G
      protein-coupled receptor signaling, receptor maturation, and desensitization. 

PMID- 24453216
TI  - Structure of sugar-bound LacY.
AB  - Here we describe the X-ray crystal structure of a double-Trp mutant (Gly46
      >Trp/Gly262->Trp) of the lactose permease of Escherichia coli (LacY) with a
      bound, high-affinity lactose analog. Although thought to be arrested in an open
      outward conformation, the structure is almost occluded and is partially open to
      the periplasmic side; the cytoplasmic side is tightly sealed. Surprisingly, the
      opening on the periplasmic side is sufficiently narrow that sugar cannot get in
      or out of the binding site. Clearly defined density for a bound sugar is observed
      at the apex of the almost occluded cavity in the middle of the protein, and the
      side chains shown to ligate the galactopyranoside strongly confirm more than two
      decades of biochemical and spectroscopic findings. Comparison of the current
      structure with a previous structure of LacY with a covalently bound inactivator
      suggests that the galactopyranoside must be fully ligated to induce an occluded
      conformation. We conclude that protonated LacY binds D-galactopyranosides
      specifically, inducing an occluded state that can open to either side of the
      membrane.

PMID- 24453217
TI  - Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion
      inhibits pathological cardiac hypertrophy.
AB  - Chronic neurohormonal and mechanical stresses are central features of heart
      disease. Increasing evidence supports a role for the transient receptor potential
      canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression
      for both is normally very low but is increased by cardiac disease, and genetic
      gain- or loss-of-function studies support contributions to hypertrophy and
      dysfunction. Selective small-molecule inhibitors remain scarce, and none target
      both channels, which may be useful given the high homology among them and
      evidence of redundant signaling. Here we tested selective TRPC3/6 antagonists
      (GSK2332255B and GSK2833503A; IC50, 3-21 nM against TRPC3 and TRPC6) and found
      dose-dependent blockade of cell hypertrophy signaling triggered by angiotensin II
      or endothelin-1 in HEK293T cells as well as in neonatal and adult cardiac
      myocytes. In vivo efficacy in mice and rats was greatly limited by rapid
      metabolism and high protein binding, although antifibrotic effects with pressure
      overload were observed. Intriguingly, although gene deletion of TRPC3 or TRPC6
      alone did not protect against hypertrophy or dysfunction from pressure overload,
      combined deletion was protective, supporting the value of dual inhibition.
      Further development of this pharmaceutical class may yield a useful therapeutic
      agent for heart disease management. 

PMID- 24453218
TI  - Dopamine prediction error responses integrate subjective value from different
      reward dimensions.
AB  - Prediction error signals enable us to learn through experience. These experiences
      include economic choices between different rewards that vary along multiple
      dimensions. Therefore, an ideal way to reinforce economic choice is to encode a
      prediction error that reflects the subjective value integrated across these
      reward dimensions. Previous studies demonstrated that dopamine prediction error
      responses reflect the value of singular reward attributes that include magnitude,
      probability, and delay. Obviously, preferences between rewards that vary along
      one dimension are completely determined by the manipulated variable. However, it
      is unknown whether dopamine prediction error responses reflect the subjective
      value integrated from different reward dimensions. Here, we measured the
      preferences between rewards that varied along multiple dimensions, and as such
      could not be ranked according to objective metrics. Monkeys chose between rewards
      that differed in amount, risk, and type. Because their choices were complete and
      transitive, the monkeys chose "as if" they integrated different rewards and
      attributes into a common scale of value. The prediction error responses of single
      dopamine neurons reflected the integrated subjective value inferred from the
      choices, rather than the singular reward attributes. Specifically, amount, risk,
      and reward type modulated dopamine responses exactly to the extent that they
      influenced economic choices, even when rewards were vastly different, such as
      liquid and food. This prediction error response could provide a direct updating
      signal for economic values. 

PMID- 24453221
TI  - Profiling of protein thiophosphorylation by Phos-tag affinity electrophoresis:
      evaluation of adenosine 5'-O-(3-thiotriphosphate) as a phosphoryl donor in
      protein kinase reactions.
AB  - Adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) has been widely used as a
      phosphoryl donor to trace protein kinase activities. However, the question
      remains whether particular kinases accept ATPgammaS as readily as they accept
      natural ATP. We investigated the characteristics of several kinase reactions in
      the presence of ATPgammaS by using Phos-tag affinity electrophoresis. The Phos
      tag gel permitted quantitative analysis of thiophosphorylated proteins produced
      by kinase reactions in vitro and it identified differences in the efficiencies of
      utilization of ATPgammaS and ATP in these reactions. Using the method, we
      evaluated the utility of ATPgammaS as a phosphoryl donor in studies on bacterial
      two-component systems. Histidine kinases accepted ATPgammaS as readily as they
      accepted ATP in autophosphorylation reactions. However, downstream
      phosphotransfer reactions with ATPgammaS were markedly slower than the
      corresponding reactions with ATP. In an analysis of the sluggish thiophosphate
      transfer, we found that detergent-denatured thiophosphorylated histidine kinases
      gradually hydrolyzed at the P-N bond, even at neutral pH, during incubation for
      24 h, whereas the native form of the thiophosphorylated enzymes were much more
      stable. Profiling of protein thiophosphorylation by using Phos-tag affinity
      electrophoresis might provide new insights into the characteristics of various
      types of kinase reactions with ATPgammaS. 

PMID- 24453220
TI  - EphB receptor forward signaling regulates area-specific reciprocal thalamic and
      cortical axon pathfinding.
AB  - In early brain development, ascending thalamocortical axons (TCAs) navigate
      through the ventral telencephalon (VTel) to reach their target regions in the
      young cerebral cortex. Descending, deep-layer cortical axons subsequently target
      appropriate thalamic and subcortical target regions. However, precisely how and
      when corticothalamic axons (CTAs) identify their appropriate, reciprocal thalamic
      targets remains unclear. We show here that EphB1 and EphB2 receptors control
      proper navigation of a subset of TCA and CTA projections through the VTel. We
      show in vivo that EphB receptor forward signaling and the ephrinB1 ligand are
      required during the early navigation of L1-CAM(+) thalamic fibers in the VTel,
      and that the misguided thalamic fibers in EphB1/2 KO mice appear to interact with
      cortical subregion-specific axon populations during reciprocal cortical axon
      guidance. As such, our findings suggest that descending cortical axons identify
      specific TCA subpopulations in the dorsal VTel to coordinate reciprocal cortical
      thalamic connectivity in the early developing brain. 

PMID- 24453224
TI  - Rat bite fever: an unusual cause of a maculopapular rash.

PMID- 24453225
TI  - Symplasmic networks in secondary vascular tissues: parenchyma distribution and
      activity supporting long-distance transport.
AB  - Stems that develop secondary vascular tissue (i.e. xylem and phloem derived from
      the vascular cambium) have unique demands on transport owing to their mass and
      longevity. Transport of water and assimilates must occur over long distances,
      while the increasing physical separation of xylem and phloem requires radial
      transport. Developing secondary tissue is itself a strong sink positioned between
      xylem and phloem along the entire length of the stem, and the integrity of these
      transport tissues must be maintained and protected for years if not decades.
      Parenchyma cells form an interconnected three-dimensional lattice throughout
      secondary xylem and phloem and perform critical roles in all of these tasks, yet
      our understanding of their physiology, the nature of their symplasmic
      connections, and their activity at the symplast-apoplast interface is very
      limited. This review highlights key historical work as well as current research
      on the structure and function of parenchyma in secondary vascular tissue in the
      hopes of spurring renewed interest in this area, which has important implications
      for whole-plant transport processes and resource partitioning.

PMID- 24453226
TI  - A 13-lipoxygenase, TomloxC, is essential for synthesis of C5 flavour volatiles in
      tomato.
AB  - C5 volatile compounds, derived from fatty acids, are among the most important
      contributors to consumer liking of fresh tomatoes. Despite their important roles
      in flavour, the genes responsible for C5 volatile synthesis have yet to be
      identified. This work shows that their synthesis is catalysed in part by a 13
      lipoxygenase (LOX), TomloxC, the same enzyme responsible for synthesis of C6
      volatiles. C5 synthesis is independent of hydroperoxide lyase (HPL); moreover,
      HPL knockdown significantly increased C5 volatile synthesis. This LOX-dependent,
      HPL-independent pathway functions in both fruits and leaves. Synthesis of C5
      volatiles increases in leaves following mechanical wounding but does not increase
      in response to infection with Xanthomonas campestris pv. vesicatoria. Large
      reductions in C5 and C6 volatiles in antisense TomloxC knockdown plants were
      observed but those reductions did not alter the development of disease symptoms,
      indicating that these volatiles do not have an important defensive function
      against this bacterial pathogen. 

PMID- 24453229
TI  - Sugar signals and the control of plant growth and development.
AB  - Sugars have a central regulatory function in steering plant growth. This review
      focuses on information presented in the past 2 years on key players in sugar
      mediated plant growth regulation, with emphasis on trehalose 6-phosphate, target
      of rapamycin kinase, and Snf1-related kinase 1 regulatory systems. The regulation
      of protein synthesis by sugars is fundamental to plant growth control, and recent
      advances in our understanding of the regulation of translation by sugars will be
      discussed.

PMID- 24453228
TI  - Peace, a MYB-like transcription factor, regulates petal pigmentation in flowering
      peach 'Genpei' bearing variegated and fully pigmented flowers.
AB  - Flowering peach Prunus persica cv. Genpei bears pink and variegated flowers on a
      single tree. The structural genes involved in anthocyanin biosynthesis were
      expressed strongly in pink petals but only very weakly or not at all in
      variegated petals. A cDNA clone encoding a MYB-like gene, isolated from pink
      petals was strongly expressed only in pink petals. Introduction of this gene, via
      biolistics gave magenta spots in the white areas of variegated petals, therefore
      this gene was named as Peace (peach anthocyanin colour enhancement). Differences
      in Peace expression determine the pattern of flower colouration in flowering
      peach. The R2R3 DNA-binding domain of Peace is similar to those of other plant
      MYBs regulating anthocyanin biosynthesis. Key amino acids for tertiary structure
      and the motif for interaction with bHLH proteins were conserved in Peace.
      Phylogenetic analysis indicates that Peace is closely related to AtMYB123 (TT2),
      which regulates proanthocyanidin biosynthesis in Arabidopsis, and to anthocyanin
      regulators in monocots rather than to regulators in dicots. This is the first
      report that a TT2-like R2R3 MYB has been shown to regulate anthocyanin
      biosynthesis. 

PMID- 24453227
TI  - Inducible knock-down of GNOM during root formation reveals tissue-specific
      response to auxin transport and its modulation of local auxin biosynthesis.
AB  - In plants, active transport of auxin plays an essential role in root development.
      Localization of the PIN1 auxin transporters to the basal membrane of cells
      directs auxin flow and depends on the trafficking mediator GNOM. GNOM-dependent
      auxin transport is vital for root development and thus offers a useful tool for
      the investigation of a possible tissue-specific response to dynamic auxin
      transport. To avoid pleiotropic effects, DEX-inducible expression of GNOM
      antisense RNA was used to disrupt GNOM expression transiently or persistently
      during embryonic root development. It was found that the elongation zone and the
      pericycle layer are the most sensitive to GNOM-dependent auxin transport
      variations, which is shown by the phenotypes in cell elongation and the
      initiation of lateral root primordia, respectively. This suggests that auxin
      dynamics is critical to cell differentiation and cell fate transition, but not to
      cell division. The results also reveal that GNOM-dependent auxin transport could
      affect local auxin biosynthesis. This suggests that local auxin biosynthesis may
      also contribute to the establishment of GNOM-dependent auxin gradients in
      specific tissues, and that auxin transport and local auxin biosynthesis may
      function together in the regulatory network for initiation and development of
      lateral root primordia. Thus, the data reveal a tissue-specific response to auxin
      transport and modulation of local auxin biosynthesis by auxin transport. 

PMID- 24453230
TI  - Wickerhamomyces arborarius f.a., sp. nov., an ascomycetous yeast species found in
      arboreal habitats on three different continents.
AB  - Five strains representing a novel yeast species belonging to the genus
      Wickerhamomyces were independently isolated from Ecuador, Taiwan and the USA. One
      strain (CLQCA 10-161(T)) was isolated from the white flower of an unidentified
      plant species collected in the Maquipucuna cloud forest reserve, near Quito, in
      Ecuador. A second strain (GY7L12) was isolated from the leaf of a Chinese sumac
      or nutgall tree (Rhus chinensis 'roxburghiana') collected in the Taoyuan mountain
      area, Kachsiung, in Taiwan. Three additional strains (A543, A546 and A563) were
      isolated from two species of wood-boring beetle (Xyleborus glabratus and
      Xyleborinus saxeseni) collected near Clyo, Georgia, USA. Analysis of the D1/D2
      domains of the LSU rRNA gene indicated that the novel species belongs to the
      genus Wickerhamomyces, and is most closely related to Wickerhamomyces sydowiorum,
      an insect-associated species predominantly found in South Africa. The North
      American and Taiwanese strains have identical internal transcribed spacer (ITS)
      sequences and can be distinguished from the Ecuadorian strain based on a single
      nucleotide substitution in the ITS1 region. The species name of Wickerhamomyces
      arborarius f.a., sp. nov. is proposed to accommodate these strains, with CLQCA 10
      161(T) ( = CBS 12941(T) = NCYC 3743(T)) designated the type strain. 

PMID- 24453231
TI  - Moheibacter sediminis gen. nov., sp. nov., a member of the family
      Flavobacteriaceae isolated from sediment, and emended descriptions of
      Empedobacter brevis, Wautersiella falsenii and Weeksella virosa.
AB  - A Gram-reaction-negative, yellow-pigmented, strictly aerobic bacterium,
      designated M0116T, was isolated from the sediment of the Mohe Basin in north-east
      China. Flexirubin-type pigments were produced. Cells were catalase- and oxidase
      positive and non-gliding rods. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain M0116T was a member of the family
      Flavobacteriaceae and was most closely related to members of the genera
      Empedobacter, Wautersiella and Weeksella with 90.5-91.0% sequence similarities.
      The major cellular fatty acids were iso-C15:0 and iso-C17:0 3-OH. The major
      respiratory quinone was MK-6 and the major polar lipid was
      phosphatidylethanolamine. The DNA G+C content was 38.2 mol%. Based on phenotypic,
      phylogenetic and genotypic data, strain M0116T is considered to represent a novel
      species of a new genus in the family Flavobacteriaceae, for which the name
      Moheibacter sediminis gen. nov., sp. nov. is proposed. The type strain is M0116T
      (=CGMCC 1.12708T=JCM 19634T). Emended descriptions of Empedobacter brevis,
      Wautersiella falsenii and Weeksella virosa are also proposed.

PMID- 24453232
TI  - Flavobacterium longum sp. nov. and Flavobacterium urocaniciphilum sp. nov.,
      isolated from a wastewater treatment plant, and emended descriptions of
      Flavobacterium caeni and Flavobacterium terrigena.
AB  - Two Gram-staining-negative, strictly aerobic, non-endospore-forming, non-motile,
      rod-shaped bacteria, designated strains YIT 12745T and YIT 12746T, were isolated
      from sludge from a wastewater treatment plant. 16S rRNA gene sequence analyses
      indicated that these strains belonged to the genus Flavobacterium. In these
      analyses, strains YIT 12745T and YIT 12746T were most closely related to the type
      strains of Flavobacterium caeni and Flavobacterium terrigena, with 16S rRNA gene
      sequence similarity values of 94.9% and 96.2%, respectively. For both novel
      strains, menaquinone (MK-6) was the only respiratory quinone. The major fatty
      acids of strain YIT 12745T were iso-C15:1 G (14.4%), iso-C16:0 (13.2%), C15:0
      (12.9%), iso-C15:0 (12.9%) and iso-C17:0 3-OH (11.5%). Those of strain YIT 12746T
      were iso-C15:0 (21.5%), iso-C16:0 (13.3%), C15:0 (12.0%) and iso-C15:1 G (11.9%).
      The genomic DNA G+C contents of strains YIT 12745T and YIT 12746T were 48.7 and
      30.9 mol%, respectively. From their differential phenotypic and phylogenetic
      characteristics, these strains are considered to represent two novel species of
      the genus Flavobacterium, for which the names Flavobacterium longum sp. nov.
      (type strain YIT 12745T=JCM 19141T=DSM 27077T) and Flavobacterium urocaniciphilum
      sp. nov. (type strain YIT 12746T=JCM 19142T=DSM 27078T) are proposed. Emended
      descriptions of Flavobacterium caeni and Flavobacterium terrigena are also
      proposed.

PMID- 24453234
TI  - Commentary: multivitamins and early pregnancy loss.

PMID- 24453233
TI  - Oceanobacillus luteolus sp. nov., isolated from soil.
AB  - Two Gram-stain-positive, rod-shaped and endospore-forming bacteria, designated WM
      1T and WM-4, were isolated from a paddy soil and a forest soil, respectively, in
      South China. Comparative 16S rRNA gene sequence analyses showed that both strains
      were members of the genus Oceanobacillus and most closely related to
      Oceanobacillus chironomi LMG 23627T with pairwise sequence similarity of 96.0%.
      The isolates contained menaquinone-7 (MK-7) as the respiratory quinone and
      anteiso-C15:0, anteiso-C17:0 and iso-C15:0 as the major fatty acids (>10%). Polar
      lipids consisted of a predominance of diphosphatidylglycerol and moderate to
      minor amounts of phosphatidylglycerol and phosphatidylinositol. The cell-wall
      peptidoglycan contained meso-diaminopimelic acid. The DNA G+C content was 38.6
      39.2 mol%. The 16S rRNA gene sequence of strain WM-1T displayed 99.7 % similarity
      to that of strain WM-4, and DNA-DNA hybridization between the two strains showed
      a relatedness value of 91 %. Based on the results of this polyphasic study,
      strains WM-1T and WM-4 represent a novel species in the genus Oceanobacillus, for
      which the name Oceanobacillus luteolus sp. nov. is proposed. The type strain is
      WM-1T (=KCTC 33119T=CGMCC 1.12406T).

PMID- 24453236
TI  - The dog-leg: an alternative to a cross-over design for pragmatic clinical trials
      in relatively stable populations.
AB  - BACKGROUND: A cross-over trial design is more powerful than a parallel groups
      design, but requires that treatment effects do not carry over from one period of
      the trial to the next. We focus here on interventions in chronic disease
      populations where the control is routine care: in such cases we cannot assume the
      intervention effect is easily washed out in crossing over from the experimental
      intervention back to the control. METHODS: We introduce an alternative trial
      design for these situations, and investigate its performance. One group is
      assessed before and after the experimental intervention, whereas two other groups
      provide respective, independent treatment comparisons in each period. We call
      this a dog-leg design because of the pattern of assessments in the three groups.
      The dog-leg design is reminiscent of a stepped wedge design, but with a reduced
      schedule of assessments and with the notable difference that not all groups
      receive the intervention. RESULTS: If the correlation between baseline and follow
      up is <0.72, the dog-leg design is more efficient than a parallel groups design
      with a baseline assessment. The dog-leg design also requires fewer assessments in
      total than a parallel groups design where participants are only assessed once, at
      follow-up. CONCLUSIONS: The dog-leg design is simple, and has some attractive
      properties. Though there is a risk of differential attrition in the three arms,
      the design's good performance relative to alternatives makes it a useful addition
      to the methodologist's toolkit.

PMID- 24453235
TI  - Periconceptional intake of vitamins and fetal death: a cohort study on
      multivitamins and folate.
AB  - BACKGROUND: Women planning to conceive are often advised to take multivitamins.
      Whether this affects the survival of the fetus is not known. METHODS: We used
      data from 35 914 women in the Danish National Birth Cohort who at recruitment had
      reported the number of weeks of supplement use during a 12-week periconceptional
      period. A telephone interview provided information about maternal characteristics
      and data on fetal death came from registers. The associations between
      periconceptional multivitamin or folate-only use and early (<20 weeks) and late
      (>=20 weeks) fetal death were estimated by hazard ratios (HR) with 95% confidence
      intervals (CI). Follow-up started at 8 completed weeks of gestation, and
      comparisons were made with no supplement use at any time during the
      periconceptional period. RESULTS: Any multivitamin use was associated with a
      small increased crude risk of fetal death [HR 1.12 (1.01-1.25)], which was
      restricted to early losses [HR 1.18 (1.05-1.33)] compared with late losses [HR
      0.82 (0.62-1.10)]. Adjustment for maternal factors increased this excess risk
      further. Whereas regular users of multivitamins (4-6 weeks of 6) before
      conception had more early losses [HR 1.29 (1.12-1.48)], a decreased risk of late
      losses was indicated when use started after conception [HR 0.65 (0.39-1.09)].
      Folate-only use was not associated with fetal death. CONCLUSIONS: Multivitamin
      use was associated with a modest increased risk of early fetal death. For late
      fetal death, regular supplement use after conception may decrease risk, but
      numbers were small. Further studies on preconceptional multivitamin use are
      needed to guide public health recommendations.

PMID- 24453237
TI  - Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual
      transmission of HCV.
AB  - BACKGROUND: HCV coinfection remains a major cause of morbidity and mortality
      among HIV-infected individuals and its incidence has increased dramatically in
      HIV-infected men who have sex with men(MSM). METHODS: Hepatitis C virus (HCV)
      coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical
      data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We
      inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission
      pairs as monophyletic patient pairs, and then considered the distribution of HCV
      on those pairs. RESULTS: Among the 9748 patients in the SHCS-DRDB with known HCV
      status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we
      identified 1555 potential HIV-1 transmission pairs. There, we found that, even
      after controlling for transmission group, calendar year, age and sex, the odds
      for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95%
      confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV
      positive case. This strong association persisted if transmission groups of
      intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered
      separately(in all cases OR>2). Finally we found that HCV incidence was increased
      by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive
      partner. CONCLUSIONS: Patients whose HIV virus is closely related to the HIV
      virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring
      HCV themselves. This indicates the occurrence of domestic and sexual HCV
      transmission and allows the identification of patients with a high HCV-infection
      risk.

PMID- 24453239
TI  - Commentary: maternal pre-pregnancy BMI and offspring ADHD: a lesson in the
      importance of testing causal pathways.

PMID- 24453238
TI  - Season of birth and other perinatal risk factors for melanoma.
AB  - BACKGROUND: Ultraviolet radiation (UVR) exposure is the main risk factor for
      cutaneous malignant melanoma (CMM), but its specific effect in infancy is
      unknown. We examined whether season of birth, a proxy for solar UVR exposure in
      the first few months of life, is associated with CMM in childhood through young
      adulthood. METHODS: National cohort study of 3,571,574 persons born in Sweden in
      1973-2008, followed up for CMM incidence through 2009 (maximum age 37 years) to
      examine season of birth and other perinatal factors. RESULTS: There were 1595 CMM
      cases in 63.9 million person-years of follow-up. We found a sinusoidal pattern in
      CMM risk by season of birth (P=0.006), with peak risk corresponding to birthdates
      in spring (March-May). Adjusted odds ratios for CMM by season of birth were 1.21
      [95% confidence interval (CI), 1.05-1.39; P=0.008] for spring, 1.07 (95% CI, 0.92
      1.24; P=0.40) for summer and 1.12 (95% CI, 0.96-1.29; P=0.14) for winter,
      relative to fall. Spring birth was associated with superficial spreading subtype
      of CMM (P=0.02), whereas there was no seasonal association with nodular subtype
      (P=0.26). Other CMM risk factors included family history of CMM in a sibling (>6
      fold) or parent (>3-fold), female gender, high fetal growth and high paternal
      education level. CONCLUSIONS: In this large cohort study, persons born in spring
      had increased risk of CMM in childhood through young adulthood, suggesting that
      the first few months of life may be a critical period of UVR susceptibility. Sun
      avoidance in early infancy may play an important role in the prevention of CMM in
      high-risk populations.

PMID- 24453240
TI  - Association of height and violent criminality: results from a Swedish total
      population study.
AB  - BACKGROUND: Violent criminality is at least moderately heritable, but the
      mechanisms behind this remain largely unexplained. Height, a highly heritable
      trait, may be involved but no study has estimated the effect of height on crime
      while simultaneously accounting for important demographic, biological and other
      heritable confounders. METHODS: We linked nationwide, longitudinal registers for
      760 000 men who underwent mandatory military conscription from 1980 through 1992
      in Sweden, to assess the association between height and being convicted of a
      violent crime. We used Cox proportional hazard modelling and controlled for three
      types of potential confounders: physical characteristics, childhood demographics
      and general cognitive ability (intelligence). RESULTS: In unadjusted analyses,
      height had a moderate negative relationship to violent crime; the shortest of men
      were twice as likely to be convicted of a violent crime as the tallest. However,
      when simultaneously controlling for all measured confounders, height was weakly
      and positively related to violent crime. Intelligence had the individually
      strongest mitigating effect on the height-crime relationship. CONCLUSIONS:
      Although shorter stature was associated with increased risk of violent offending,
      our analyses strongly suggested that this relationship was explained by
      intelligence and other confounding factors. Hence, it is unlikely that height, a
      highly heritable physical characteristic, accounts for much of the unexplained
      heritability of violent criminality.

PMID- 24453241
TI  - Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins:
      kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity,
      and protection across serotypes.
AB  - Shigella is one of the leading pathogens contributing to the vast pediatric
      diarrheal disease burden in low-income countries. No licensed vaccine is
      available, and the existing candidates are only partially effective and serotype
      specific. Shigella type III secretion system proteins IpaB and IpaD, which are
      conserved across Shigella spp., are candidates for a broadly protective, subunit
      based vaccine. In this study, we investigated the immunogenicity and protective
      efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant
      of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using
      microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT,
      were tested in mice. Vaccine delivery into the dermis, recruitment of
      neutrophils, macrophages, dendritic cells, and Langerhans cells, and
      colocalization of vaccine Ag within skin-activated APC were demonstrated through
      histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages,
      dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB,
      IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced
      following i.d. immunization. The protective efficacy was 70% against Shigella
      flexneri and 50% against Shigella sonnei. Similar results were obtained when the
      vaccine was administered intranasally, with the i.d. route requiring 25-40 times
      lower doses. Distinctively, IgG was detected in mucosal secretions; secretory
      IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly
      absent. Vaccine-induced T cells produced IFN-gamma, IL-2, TNF-alpha, IL-17, IL-4,
      IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with
      IpaB and IpaD to prevent Shigella infection and support further studies in
      humans. 

PMID- 24453242
TI  - IL-37 ameliorates the inflammatory process in psoriasis by suppressing
      proinflammatory cytokine production.
AB  - IL-37 is a potent inhibitor of innate immunity by shifting the cytokine
      equilibrium away from excessive inflammation. Psoriasis is thought to be
      initiated by abnormal interactions between the cutaneous keratinocytes and
      systemic immune cells, triggering keratinocyte hyperproliferation. In the current
      study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte
      cell line (HaCaT) and the keratin 14 VEGF-A-transgenic mouse model. First, we
      used the HaCaT cell line, which was transiently transfected with an
      overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using
      a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing
      the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the
      mixture of five proinflammatory cytokines. Keratin 14 VEGF-A-transgenic mice were
      treated with plasmid coding human IL-37 sequence-formulated cationic liposomes,
      and we observed potent immunosuppressive effects over the 18-d period. In this
      model, we observed reduced systemic IL-10 levels, local IFN-gamma gene
      transcripts, as well as mild mast cell infiltration into the psoriatic lesions of
      the mice. Immunohistochemical analysis indicated that IL-37 was expressed by
      effector memory T cells, as well as macrophages, in human psoriatic plaques. In
      conclusion, our studies strongly indicate that IL-37 plays a potent
      immunosuppressive role in the pathogenesis of both experimental psoriasis models
      in vitro and in vivo by downregulating proinflammatory cytokines. Importantly,
      our findings highlight new therapeutic strategies that can be designed to use
      this immunosuppressive anti-inflammatory cytokine in psoriasis and other
      inflammatory cutaneous diseases. 

PMID- 24453243
TI  - Bruton's tyrosine kinase promotes persistence of mature anti-insulin B cells.
AB  - Autoreactive B lymphocytes are essential for the development of T cell-mediated
      type 1 diabetes (T1D). Cytoplasmic Bruton's tyrosine kinase (BTK) is a key
      component of B cell signaling, and its deletion in T1D-prone NOD mice
      significantly reduces diabetes. However, the role of BTK in the survival and
      function of autoreactive B cells is not clear. To evaluate the contributions of
      BTK, we used mice in which B cells express an anti-insulin BCR (125Tg) and
      promote T1D, despite being anergic. Crossing Btk deficiency onto 125Tg mice
      reveals that, in contrast to immature B cells, mature anti-insulin B cells are
      exquisitely dependent upon BTK, because their numbers are reduced by 95%. BTK
      kinase domain inhibition reproduces this effect in mature anti-insulin B cells,
      with less impact at transitional stages. The increased dependence of anti-insulin
      B cells on BTK became particularly evident in an Igkappa locus site-directed
      model, in which 50% of B cells edit their BCRs to noninsulin specificities; Btk
      deficiency preferentially depletes insulin binders from the follicular and
      marginal zone B cell subsets. The persistent few Btk-deficient anti-insulin B
      cells remain competent to internalize Ag and invade pancreatic islets. As such,
      loss of BTK does not significantly reduce diabetes incidence in 125Tg/NOD mice as
      it does in NOD mice with a normal B cell repertoire. Thus, BTK targeting may not
      impair autoreactive anti-insulin B cell function, yet it may provide protection
      in an endogenous repertoire by decreasing the relative availability of mature
      autoreactive B cells. 

PMID- 24453245
TI  - FLT3-ligand treatment of humanized mice results in the generation of large
      numbers of CD141+ and CD1c+ dendritic cells in vivo.
AB  - We established a humanized mouse model incorporating FLT3-ligand (FLT3-L)
      administration after hematopoietic cell reconstitution to investigate expansion,
      phenotype, and function of human dendritic cells (DC). FLT3-L increased numbers
      of human CD141(+) DC, CD1c(+) DC, and, to a lesser extent, plasmacytoid DC (pDC)
      in the blood, spleen, and bone marrow of humanized mice. CD1c(+) DC and CD141(+)
      DC subsets were expanded to a similar degree in blood and spleen, with a bias
      toward expansion of the CD1c(+) DC subset in the bone marrow. Importantly, the
      human DC subsets generated after FLT3-L treatment of humanized mice are
      phenotypically and functionally similar to their human blood counterparts.
      CD141(+) DC in humanized mice express C-type lectin-like receptor 9A, XCR1,
      CADM1, and TLR3 but lack TLR4 and TLR9. They are major producers of IFN-lambda in
      response to polyinosinic-polycytidylic acid but are similar to CD1c(+) DC in
      their capacity to produce IL-12p70. Although all DC subsets in humanized mice are
      efficient at presenting peptide to CD8(+) T cells, CD141(+) DC are superior in
      their capacity to cross-present protein Ag to CD8(+) T cells following activation
      with polyinosinic-polycytidylic acid. CD141(+) DC can be targeted in vivo
      following injection of Abs against human DEC-205 or C-type lectin-like receptor
      9A. This model provides a feasible and practical approach to dissect the function
      of human CD141(+) and CD1c(+) DC and evaluate adjuvants and DC-targeting
      strategies in vivo. 

PMID- 24453244
TI  - Embryonic trophoblasts induce decidual regulatory T cell differentiation and
      maternal-fetal tolerance through thymic stromal lymphopoietin instructing
      dendritic cells.
AB  - Physiological pregnancy requires the maternal immune system to recognize and
      tolerate embryonic Ags. Although multiple mechanisms have been proposed, it is
      not yet clear how the fetus evades the maternal immune system. In this article,
      we demonstrate that trophoblast-derived thymic stromal lymphopoietin (TSLP)
      instructs decidual CD11c(+) dendritic cells (dDCs)with increased costimulatory
      molecules; MHC class II; and Th2/3-type, but not Th1-type, cytokines. TSLP
      activated dDCs induce proliferation and differentiation of decidual CD4(+)CD25(-)
      T cells into CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) through TGF-beta1.
      TSLP-activated dDC-induced Tregs display immunosuppressive features and express
      Th2-type cytokines. In addition, decidual CD4(+)CD25(+)FOXP3(+) Tregs promote
      invasiveness and HLA-G expression of trophoblasts, resulting in preferential
      production of Th2 cytokines and reduced cytotoxicity in decidual
      CD56(bright)CD16(-) NK cells. Of interest, decreased TSLP expression and reduced
      numbers of Tregs were observed at the maternal-fetal interface during
      miscarriage. Our study identifies a novel feedback loop between embryo-derived
      trophoblasts and maternal decidual leukocytes, which induces a tolerogenic immune
      response to ensure a successful pregnancy. 

PMID- 24453246
TI  - KIR3DL01 recognition of Bw4 ligands in the rhesus macaque: maintenance of Bw4
      specificity since the divergence of apes and Old World monkeys.
AB  - The identification of MHC class I ligands for rhesus macaque killer cell Ig-like
      receptors (KIRs) is fundamental to our basic understanding of KIR and MHC class I
      coevolution and to the study of NK cell responses in this nonhuman primate model
      for AIDS and other viral diseases. In this study, we show that Mamu-KIR3DL01,
      which is expressed by ~90% of rhesus macaques, recognizes MHC class I molecules
      with a Bw4 motif. Primary NK cells expressing Mamu-KIR3DL01 were identified by
      staining with a mAb which, in this study, was shown to bind Mamu-KIR3DL01
      allotypes with an aspartic acid at position 233. The cytolytic activity of Mamu
      KIR3DL01(+) NK cells was suppressed by cell lines expressing the Bw4 molecules
      Mamu-B*007:01, -B*041:01, -B*058:02, and -B*065:01. The Bw4 motif was necessary
      for Mamu-KIR3DL01 recognition because substitutions in this region abrogated Mamu
      KIR3DL01(+) NK cell inhibition. However, the presence of a Bw4 motif was not
      sufficient for recognition because another Bw4 molecule, Mamu-B*017:01, failed to
      suppress the cytolytic activity of these NK cells. Replacement of three residues
      in Mamu-B*017:01, predicted to be KIR contacts based on the three-dimensional
      structure of the human KIR3DL1-HLA-Bw4 complex, with the corresponding residues
      at these positions for the other Mamu-Bw4 ligands restored Mamu-KIR3DL01(+) NK
      cell inhibition. These results define the ligand specificity of one of the most
      polymorphic and commonly expressed KIRs in the rhesus macaque and reveal
      similarities in Bw4 recognition by Mamu-KIR3DL01 and human KIR3DL1, despite the
      absence of an orthologous relationship between these two KIRs or conservation of
      surface residues predicted to interact with MHC class I ligands. 

PMID- 24453248
TI  - Oral combined therapy with probiotics and alloantigen induces B cell-dependent
      long-lasting specific tolerance.
AB  - Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the
      treatment of hematologic malignancies. Although aHSCT provides a good response
      against the malignant cells (graft-versus-leukemia [GVL]), it also leads to the
      development of graft-versus-host disease (GVHD), a severe disease with high
      mortality and morbidity rates. Therapy for GVHD is commonly based on nonspecific
      immunosupression of the transplanted recipient, resulting in the concomitant
      inhibition of the GVL effect. In this study, we propose an alternative approach
      to specifically suppress GVHD while sparing the GVL, based on oral treatment of
      transplant donors with recipient Ags, associated with the intake of probiotic
      Lactococcus lactis as tolerogenic adjuvant (combined therapy). We show that
      treatment of C57BL/6 donor mice with combined therapy before the transplant
      protects the recipients F1 (C57BL/6 * BAL/c) mice from clinical and pathological
      manifestations of disease, resulting in 100% survival rate. Importantly, the
      animals keep the immunological competence maintaining the GVL response as well as
      the response to third-party Ags. The protection is specific, long lasting and
      dependent on donor IL-10-sufficient B cells activity, which induces regulatory T
      cells in the host. These data suggest that combined therapy is a promising
      strategy for prevention of GVHD with preservation of GVL, opening new
      possibilities to treat human patients subjected to transplantation. 

PMID- 24453247
TI  - Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary
      inflammation independently from its role in sensitization.
AB  - The myeloid C-type lectin receptor Dectin-2 directs the generation of Th2 and
      Th17 immune responses to the house dust mite Dermatophagoides farinae through the
      generation of cysteinyl leukotrienes and proinflammatory cytokines, respectively,
      but a role for Dectin-2 in effector phase responses has not been described. In
      this study, we demonstrate that administration of the Dectin-2 mAb solely at the
      time of D. farinae challenge abrogated eosinophilic and neutrophilic inflammation
      in the bronchoalveolar lavage fluid and Th1, Th2, and Th17 inflammation in the
      lung of previously sensitized mice. Furthermore, Dectin-2 null mice (Clec4n(-/-))
      sensitized with the adoptive transfer of D. farinae-pulsed wild-type (WT) bone
      marrow-derived dendritic cells (DCs) also had less D. farinae-elicited pulmonary
      inflammation, supporting an effector function for Dectin-2. The protection from
      pulmonary inflammation seen with the Dectin-2 mAb or in Clec4n(-/-) mice was
      associated with little or no reduction in lung-draining lymph node cells or their
      cytokine production and with no reduction in serum IgE. WT and Clec4n(-/-) mice
      recipients, sensitized with D. farinae-pulsed WT bone marrow-derived DCs, had
      comparable levels of D. farinae-elicited IL-6, IL-23, TNF-alpha, and cysteinyl
      leukotrienes in the lung. By contrast, D. farinae-elicited CCL4 and CCL8
      production from pulmonary CD11c(+)CD11b(+)Ly6C(+) and CD11c(+)CD11b(+)Ly6C(
      )CD64(+) monocyte-derived DCs was reduced in Clec4n(-/-) recipients. Addition of
      CCL8 at the time of D. farinae challenge abrogated the protection from
      eosinophilic, neutrophilic, and Th2 pulmonary inflammation seen in Clec4n(-/-)
      recipients. Taken together, these results reveal that Dectin-2 regulates monocyte
      derived DC function in the pulmonary microenvironment at D. farinae challenge to
      promote the local inflammatory response. 

PMID- 24453249
TI  - CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1
      in children with mild malaria.
AB  - The immune response against the variant surface Ag Plasmodium falciparum
      erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity
      against malaria. We have investigated the development and maintenance of CD4(+) T
      cell responses to a small semiconserved area of the Duffy binding-like domain
      (DBL)alpha-domain of PfEMP1, the DBLalpha-tag. Young children were followed up
      longitudinally, and parasites and PBMCs were isolated from 35 patients presenting
      with an acute case of uncomplicated malaria. The DBLalpha-tag from the PfEMP1
      dominantly expressed by the homologous parasite isolate was cloned and expressed
      as recombinant protein. The recombinant DBLalpha-tag was used to activate PBMCs
      collected from each acute episode and from an annual cross-sectional survey
      performed after the acute malaria episode. In this article, we report that CD4(+)
      T cell responses to the homologous DBLalpha-tag were induced in 75% of the
      children at the time of the acute episode and in 62% of the children at the
      following cross-sectional survey on average 235 d later. Furthermore, children
      who had induced DBLalpha-tag-specific CD4(+)IL-4(+) T cells at the acute episode
      remained episode free for longer than children who induced other types of CD4(+)
      T cell responses. These results suggest that a wide range of DBLalpha-tag
      specific CD4(+) T cell responses were induced in children with mild malaria and,
      in the case of CD4(+)IL-4(+) T cell responses, were associated with protection
      from clinical episodes. 

PMID- 24453251
TI  - Binding of HLA-G to ITIM-bearing Ig-like transcript 2 receptor suppresses B cell
      responses.
AB  - Inhibition of B cells constitutes a rational approach for treating B cell
      mediated disorders. We demonstrate in this article that the engagement of the
      surface Ig-like transcript 2 (ILT2) inhibitory receptor with its preferential
      ligand HLA-G is critical to inhibit B cell functions. Indeed, ILT2-HLA-G
      interaction impedes both naive and memory B cell functions in vitro and in vivo.
      Particularly, HLA-G inhibits B cell proliferation, differentiation, and Ig
      secretion in both T cell-dependent and -independent models of B cell activation.
      HLA-G mediates phenotypic and functional downregulation of CXCR4 and CXCR5
      chemokine receptors on germinal center B cells. In-depth analysis of the
      molecular mechanisms mediated by ILT2-HLA-G interaction showed a G0/G1 cell cycle
      arrest through dephosphorylation of AKT, GSK-3beta, c-Raf, and Foxo proteins.
      Crucially, we provide in vivo evidence that HLA-G acts as a negative B cell
      regulator in modulating B cell Ab secretion in a xenograft mouse model. This B
      cell regulatory mechanism involving ILT2-HLA-G interaction brings important
      insight to design future B cell-targeted therapies aimed at reducing
      inappropriate immune reaction in allotransplantation and autoimmune diseases. 

PMID- 24453250
TI  - B cell depletion curtails CD4+ T cell memory and reduces protection against
      disseminating virus infection.
AB  - Dynamic interactions between CD4(+) T cells and B cells are needed for humoral
      immunity and CD4(+) T cell memory. It is not known whether B cells are needed
      early on to induce the formation of memory precursor cells or are needed later to
      sustain memory cells. In this study, primary and memory CD4(+) T cells responses
      were followed in wild-type mice that were depleted of mature B cells by anti-CD20
      before or different times after acute lymphocytic choriomeningitis virus
      infection. The Ab treatment led to a 1000-fold reduction in B cell number that
      lasted 6 wk. Primary virus-specific CD4(+) Th1 cells were generated in B cell
      depleted mice; however, there was a decrease in the CD4(+)Ly6C(lo)Tbet(+) memory
      precursor population and a corresponding 4-fold reduction in CD4(+) memory cell
      number. Memory T cells showed impaired cytokine production when they formed
      without B cells. B cell depletion had no effect on established memory
      populations. During disseminating virus infection, B cell depletion led to
      sustained weight loss and functional exhaustion of CD4(+) and CD8(+) T cells, and
      prevented mice from resolving the infection. Thus, B cells contribute to the
      establishment and survival of memory CD4(+) T cells post-acute infection and play
      an essential role in immune protection against disseminating virus infection. 

PMID- 24453252
TI  - Mst1/Mst2 regulate development and function of regulatory T cells through
      modulation of Foxo1/Foxo3 stability in autoimmune disease.
AB  - Foxp3 expression and regulatory T cell (Treg) development are critical for
      maintaining dominant tolerance and preventing autoimmune diseases. Human MST1
      deficiency causes a novel primary immunodeficiency syndrome accompanied by
      autoimmune manifestations. However, the mechanism by which Mst1 controls immune
      regulation is unknown. In this article, we report that Mst1 regulates Foxp3
      expression and Treg development/function and inhibits autoimmunity through
      modulating Foxo1 and Foxo3 (Foxo1/3) stability. We have found that Mst1
      deficiency impairs Foxp3 expression and Treg development and function in mice.
      Mechanistic studies reveal that Mst1 enhances Foxo1/3 stability directly by
      phosphorylating Foxo1/3 and indirectly by attenuating TCR-induced Akt activation
      in peripheral T cells. Our studies have also shown that Mst1 deficiency does not
      affect Foxo1/3 cellular localization in CD4 T cells. In addition, we show that
      Mst1(-/-) mice are prone to autoimmune disease, and mutant phenotypes, such as
      overactivation of naive T cells, splenomegaly, and autoimmune pathological
      changes, are suppressed in Mst1(-/-) bone marrow chimera by cotransplanted wt
      Tregs. Finally, we demonstrate that Mst1 and Mst2 play a partially redundant role
      in Treg development and autoimmunity. Our findings not only identify Mst kinases
      as the long-searched-for factors that simultaneously activate Foxo1/3 and inhibit
      TCR-stimulated Akt downstream of TCR signaling to promote Foxp3 expression and
      Treg development, but also shed new light on understanding and designing better
      therapeutic strategies for MST1 deficiency-mediated human immunodeficiency
      syndrome. 

PMID- 24453253
TI  - A spliced antigenic peptide comprising a single spliced amino acid is produced in
      the proteasome by reverse splicing of a longer peptide fragment followed by
      trimming.
AB  - Peptide splicing is a novel mechanism of production of peptides relying on the
      proteasome and involving the linkage of fragments originally distant in the
      parental protein. Peptides produced by splicing can be presented on class I
      molecules of the MHC and recognized by CTLs. In this study, we describe a new
      antigenic peptide, which is presented by HLA-A3 and comprises two noncontiguous
      fragments of the melanoma differentiation Ag gp100(PMEL17) spliced together in
      the reverse order to that in which they appear in the parental protein. Contrary
      to the previously described spliced peptides, which are produced by the
      association of fragments of 3-6 aa, the peptide described in this work results
      from the ultimate association of an 8-aa fragment with a single arginine residue.
      As described before, peptide splicing takes place in the proteasome by
      transpeptidation involving an acyl-enzyme intermediate linking one of the peptide
      fragment to a catalytic subunit of the proteasome. Interestingly, we observe that
      the peptide causing the nucleophilic attack on the acyl-enzyme intermediate must
      be at least 3 aa long to give rise to a spliced peptide. The spliced peptide
      produced from this reaction therefore bears an extended C terminus that needs to
      be further trimmed to produce the final antigenic peptide. We show that the
      proteasome is able to perform the final trimming step required to produce the
      antigenic peptide described in this work. 

PMID- 24453254
TI  - MMTV superantigens coerce an unconventional topology between the TCR and MHC
      class II.
AB  - Mouse mammary tumor virus superantigens (vSAGs) are notorious for defying
      structural characterization, and a consensus has yet to be reached regarding
      their ability to bridge the TCR to MHC class II (MHCII). In this study, we
      determined the topology of the T cell signaling complex by examining the
      respective relation of vSAG7 with the MHCII molecule, MHCII-associated peptide,
      and TCR. We used covalently linked peptide/MHCII complexes to demonstrate that
      vSAG presentation is tolerant to variation in the protruding side chains of the
      peptide, but can be sensitive to the nature of the protruding N-terminal
      extension. An original approach in which vSAG was covalently linked to either
      MHCII chain confirmed that vSAG binds outside the peptide binding groove. Also,
      whereas the C-terminal vSAG segment binds to the MHCII alpha-chain in a
      conformation-sensitive manner, the membrane-proximal N-terminal domain binds the
      beta-chain. Because both moieties of the mature vSAG remain noncovalently
      associated after processing, our results suggest that vSAG crosslinks MHCII
      molecules. Comparing different T cell hybridomas, we identified key residues on
      the MHCII alpha-chain that are differentially recognized by the CDR3beta when
      engaged by vSAG. Finally, we show that the highly conserved tyrosine residue
      found in the vSAg TGXY motif is required for T cell activation. Our results
      reveal a novel SAG/MHCII/TCR architecture in which vSAGs coerce a near-canonical
      docking between MHCII and TCR that allows eschewing of traditional CDR3 binding
      with the associated peptide in favor of MHCII alpha-chain binding. Our findings
      highlight the plasticity of the TCR CDRs. 

PMID- 24453255
TI  - FADD and caspase-8 mediate priming and activation of the canonical and
      noncanonical Nlrp3 inflammasomes.
AB  - The Nlrp3 inflammasome is critical for host immunity, but the mechanisms
      controlling its activation are enigmatic. In this study, we show that loss of
      FADD or caspase-8 in a RIP3-deficient background, but not RIP3 deficiency alone,
      hampered transcriptional priming and posttranslational activation of the
      canonical and noncanonical Nlrp3 inflammasome. Deletion of caspase-8 in the
      presence or absence of RIP3 inhibited caspase-1 and caspase-11 activation by
      Nlrp3 stimuli but not the Nlrc4 inflammasome. In addition, FADD deletion
      prevented caspase-8 maturation, positioning FADD upstream of caspase-8.
      Consequently, FADD- and caspase-8-deficient mice had impaired IL-1beta production
      when challenged with LPS or infected with the enteropathogen Citrobacter
      rodentium. Thus, our results reveal FADD and caspase-8 as apical mediators of
      canonical and noncanonical Nlrp3 inflammasome priming and activation. 

PMID- 24453256
TI  - PTPN22 controls the germinal center by influencing the numbers and activity of T
      follicular helper cells.
AB  - A single nucleotide polymorphism in PTPN22 (R620W), which encodes the Lyp
      tyrosine phosphatase, has been linked to a number of autoimmune diseases
      including type 1 diabetes, rheumatoid arthritis, and systemic lupus
      erythematosus. Studies in PTPN22 knockout (KO) mice and in mice expressing the
      mouse homolog of the pro-autoimmune allele, PEP(R619W), have reported increased
      germinal center activity and enhanced Ab production. In this article, we present
      findings that explain the basis for increased germinal center activity in PTPN22
      mutant mice. As compared with their wild type equivalents, T follicular helper
      cells from PTPN22 KO mice proliferate and accumulate to a greater extent, and
      exhibit enhanced production of IL-21. The follicular regulatory T cells in PTPN22
      KO mice do not expand to effectively regulate these T follicular helper cells,
      resulting in an increase in B cell numbers and Ab production. This is evident in
      the KBxN mouse model of arthritis in which PTPN22 deficiency results in increased
      severity of disease. Our findings demonstrate the importance of cell type
      specific PTPN22 activity on regulation of Ab production. 

PMID- 24453257
TI  - Infection and cellular defense dynamics in a novel 17beta-estradiol murine model
      of chronic human group B streptococcus genital tract colonization reveal a role
      for hemolysin in persistence and neutrophil accumulation.
AB  - Genital tract carriage of group B streptococcus (GBS) is prevalent among adult
      women; however, the dynamics of chronic GBS genital tract carriage, including how
      GBS persists in this immunologically active host niche long term, are not well
      defined. To our knowledge, in this study, we report the first animal model of
      chronic GBS genital tract colonization using female mice synchronized into estrus
      by delivery of 17beta-estradiol prior to intravaginal challenge with wild-type
      GBS 874391. Cervicovaginal swabs, which were used to measure bacterial
      persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers
      (10(6)-10(7) CFU/swab) for at least 90 d. Cellular and histological analyses
      showed that chronic GBS colonization of the murine genital tract caused
      significant lymphocyte and PMN cell infiltrates, which were localized to the
      vaginal mucosal surface. Long-term colonization was independent of regular
      hormone cycling. Immunological analyses of 23 soluble proteins related to
      chemotaxis and inflammation showed that the host response to GBS in the genital
      tract comprised markers of innate immune activation including cytokines such as
      GM-CSF and TNF-alpha. A nonhemolytic isogenic mutant of GBS 874391, Deltacyle9,
      was impaired for colonization and was associated with amplified local PMN
      responses. Induction of DNA neutrophil extracellular traps, which was observed in
      GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be
      part of this response. Overall, this study defines key infection dynamics in a
      novel murine model of chronic GBS genital tract colonization and establishes
      previously unknown cellular and soluble defense responses to GBS in the female
      genital tract. 

PMID- 24453258
TI  - Mast cells contribute to bleomycin-induced lung inflammation and injury in mice
      through a chymase/mast cell protease 4-dependent mechanism.
AB  - Mast cells (MCs) are found in large numbers in lungs of patients with pulmonary
      fibrosis. However, the functions of MCs in lung fibrosis remain largely unknown.
      We assessed the role of MCs and MC protease 4 (MCPT4), the mouse counterpart of
      human MC chymase, in a mouse model of bleomycin (BLM)-induced lung injury. We
      found that levels of inflammation in the bronchoalveolar lavage and the lung, as
      well as levels of lung fibrosis, were reduced 7 d after intranasal delivery of
      BLM MC-deficient Kit(W-sh/W-sh) mice compared with wild-type (WT) mice.
      Confirming the implication of MCs in these processes, we report that the levels
      of inflammation and fibrosis observed in Kit(W-sh/W-sh) mice can be restored to
      those observed in WT mice after the adoptive transfer of bone marrow-derived
      cultured MCs into Kit(W-sh/W-sh) mice. Additionally, we show that levels of
      inflammation and fibrosis are also reduced in MC chymase MCPT4-deficient mice as
      compared with WT mice at day 7, suggesting a role for MC-derived MCPT4 in these
      processes. Our results support the conclusion that MCs can contribute to the
      initial lung injury induced by BLM through release of the MCPT4 chymase. 

PMID- 24453259
TI  - Computational approach to characterize causative factors and molecular indicators
      of chronic wound inflammation.
AB  - Chronic inflammation is rapidly becoming recognized as a key contributor to
      numerous pathologies. Despite detailed investigations, understanding of the
      molecular mechanisms regulating inflammation is incomplete. Knowledge of such
      critical regulatory processes and informative indicators of chronic inflammation
      is necessary for efficacious therapeutic interventions and diagnostic support to
      clinicians. We used a computational modeling approach to elucidate the critical
      factors responsible for chronic inflammation and to identify robust molecular
      indicators of chronic inflammatory conditions. Our kinetic model successfully
      captured experimentally observed cell and cytokine dynamics for both acute and
      chronic inflammatory responses. Using sensitivity analysis, we identified
      macrophage influx and efflux rate modulation as the strongest inducing factor of
      chronic inflammation for a wide range of scenarios. Moreover, our model predicted
      that, among all major inflammatory mediators, IL-6, TGF-beta, and PDGF may
      generally be considered the most sensitive and robust indicators of chronic
      inflammation, which is supported by existing, but limited, experimental evidence.

PMID- 24453260
TI  - In menopausal women physical activity and taking dietary supplements may protect
      against coronary artery disease.

PMID- 24453261
TI  - Immunity status against influenza A subtype H7N9 and other avian influenza
      viruses in a high-risk group and the general population in India.

PMID- 24453262
TI  - Reply to Pawar et al.

PMID- 24453263
TI  - Does the use of antipyretics prolong the duration of fever or illness?

PMID- 24453264
TI  - Acute tamponade of the left paracorporeal pump house due to membrane defect in a
      patient with a Berlin Heart EXCOR biventricular assist device.
AB  - We report a case of acute tamponade of the left paracorporeal pump house in a
      patient supported by a Berlin Heart EXCOR biventricular assist device (BiVAD)
      caused by mechanical defect in the membrane of the arterial chamber. A 36-year
      old male was admitted for composite graft surgery due to a large aortic
      regurgitation and consecutive heart failure, decompensated postoperatively and
      was rescued by with an extracorporeal membrane oxygenation (ECMO) device. He was
      accepted for heart transplantation, and a BiVAD (Berlin Heart EXCOR) was
      implanted as bridge-to-transplantation. Two months after discharge, he
      experienced dyspnoea and received error signals from his BiVAD. Relatives
      released him from his BiVAD companion driver, connected him to the hand pump and
      transported him to our institution. On arrival, he was in cardiogenic shock and
      was stabilized by ECMO. Inspection of the arterial chamber revealed a wear hole
      and delamination of the diaphragm, which had led to a tamponade by air
      insufflation into the three-layer membrane. New BiVAD paracorporeal pumps were
      connected, and the patient was subsequently successfully transplanted. The case
      depicts the difficulty of diagnosis in this specific patient setting. Despite
      transparent design of the BiVAD chambers, the development of a chamber tamponade
      remained undetected until explantation of the system. 

PMID- 24453265
TI  - Observations in lung cancer over multiple decades: an analysis of outcomes and
      cost at a single high-volume institution.
AB  - OBJECTIVES: This study reviews survival outcomes and cost of lung cancer care
      over multiple decades at a single high-volume institution. METHODS: All patients
      with a diagnosis of lung cancer were analysed at a single institution from 1959
      to 2010. Data were extracted from a tumour registry, which was linked to a
      longitudinal medical record, clinical data repository and social security master
      death index. In-depth survival analyses by stage were performed using Kaplan
      Meier methods from 1981 to 2010. The analysis contains hospital billing data on
      1025 lung cancer patients from 2004 to 2010. RESULTS: A total of 17 025 patients
      with lung cancer were identified over the study period. The 1-year, 5-year and 10
      year all-cause mortality rates were 41, 78 and 87%, respectively. Non-small-cell
      lung cancer comprised 73% (n = 12 361) of cases where the median survival = 2.5
      years and the population was 94% Caucasian. Lung cancer was most prevalent
      between ages 60-79 years of life. Female gender and adenocarcinoma were
      increasingly more prevalent over the decades. The 5-, 10- and 15-year survival
      for non-small-cell lung cancer (NSCLC) patients were 27, 15 and 5%, respectively.
      Death rates measured at 1 year after diagnosis were reduced; however, 5-year
      survival over each subsequent decade did not significantly change. In patients
      where the full scope of cost data were available, the median cost/patient with
      any stage NSCLC = $40 500, where 63% of the cost is expended in the first year
      after diagnosis. The average length of treatment for NSCLC was 20.2 months. The
      greatest single category of expense was chemotherapy (31%), followed by surgery
      (24%), inpatient medical (17%), radiation therapy (12%) and diagnostics (5%). For
      surgically treated patients, Stage II-IV costs were roughly twice those of Stage
      I. CONCLUSIONS: There has been no evident improvement over the past 3 decades in
      5-year survival (~27%) in patients diagnosed with NSCLC at a single high-volume
      institution. Improvement in 1-year survival is thought to be attributed to
      improvements in diagnosing lung cancer earlier. Most of the healthcare
      expenditure for lung cancer is incurred during the first year after diagnosis
      despite stage.

PMID- 24453267
TI  - Patients with prolonged disorders of consciousness: more than a clinical
      challenge.

PMID- 24453266
TI  - Comparison of the Ross/Ross-Konno aortic root in children before and after the
      age of 18 months.
AB  - OBJECTIVES: Evaluation of long-term results after the Ross/Ross-Konno operation
      in patients <18 months of age, focusing on pulmonary autograft performance.
      METHODS: Retrospective analysis of patients who underwent the Ross/Ross-Konno
      operation (1991-2011). Data were obtained from hospital records and follow-up was
      100% complete. RESULTS: Between January 1991 and December 2011, 140 patients
      underwent the Ross/Ross-Konno operation and 22 patients were <18 months of age
      (male/female: 15/7). The median age was 166 days. 14 patients had a Ross
      operation and 8 patients a Ross-Konno operation. Presentation at surgery was
      aortic valve stenosis in 13, regurgitation in 7 and mixed disease in 2. Only 4
      patients (18%) had no surgery prior to Ross/Ross-Konno, and among the others the
      previous most frequent operation was aortic valvotomy (55%). There were 3 early
      deaths, all in high-risk cases with poor preoperative left ventricular function.
      At discharge there was no neoaortic regurgitation in 10, trivial in 4 and mild in
      5. The median follow-up is 10.8 years (range 0.96-21). There was 1 late death due
      to progressive ventricular dysfunction 2.4 years after Ross-Konno and mitral
      valve replacement. Survival for patients <18 months was 81% at 5-10 years (18
      patients) and for older patients was 98.2% at 5-10 years. There was no neoaortic
      regurgitation in 8 patients, mild in another 8 and moderate in 2 with a freedom
      from moderate regurgitation significantly lower in comparison with older patients
      (100-80% vs 83.5-73.4% at 5-10 years). Freedom from aortic reoperation for
      patients <18 months was significantly higher compared with older (100 vs 95.4
      84.4% at 5-10 years, P < 0.04). Reoperation in the RVOT was higher in younger
      patients compared with the other (85-64.6% vs 97.2 and 84.7% at 5-10 years P =
      0.02). Z-score aortic root diameter remained constant in the <18-months group
      compared with significant dilatation in the >18-months patients (P < 0.01).
      CONCLUSIONS: Ross/Ross-Konno can be invaluable in the younger age group but not
      without risk in the setting of ventricular dysfunction. Long-term performance of
      the neoaortic valve is significantly better than in older children, which is
      related to maintenance of normal root dimensions compared with progressive
      dilatation in patients undergoing Ross/Ross-Konno at older ages.

PMID- 24453268
TI  - Using Option Grids: a referee's commentary.

PMID- 24453270
TI  - Rules of tongue: look, listen, feel.

PMID- 24453269
TI  - Transient ischaemic attacks: mimics and chameleons.
AB  - Suspected transient ischaemic attack (TIA) is a common diagnostic challenge for
      physicians in neurology, stroke, general medicine and primary care. It is
      essential to identify TIAs promptly because of the very high early risk of
      ischaemic stroke, requiring urgent investigation and preventive treatment. On the
      other hand, it is also important to identify TIA 'mimics', to avoid unnecessary
      and expensive investigations, incorrect diagnostic labelling and inappropriate
      long-term prevention treatment. Although the pathophysiology of ischaemic stroke
      and TIA is identical, and both require rapid and accurate diagnosis, the
      differential diagnosis differs for TIA owing to the transience of symptoms. For
      TIA the diagnostic challenge is greater, and the 'mimic' rate higher (and more
      varied), because there is no definitive diagnostic test. TIA heralds a high risk
      of early ischaemic stroke, and in many cases the stroke can be prevented if the
      cause is identified, hence the widespread dissemination of guidelines including
      rapid assessment and risk tools like the ABCD2 score. However, these guidelines
      do not emphasise the substantial challenges in making the correct diagnosis in
      patients with transient neurological symptoms. In this article we will mainly
      consider the common TIA mimics, but also briefly mention the rather less common
      situations where TIAs can look like something else ('chameleons'). 

PMID- 24453272
TI  - Soy intake and breast cancer risk: an evaluation based on a systematic review of
      epidemiologic evidence among the Japanese population.
AB  - OBJECTIVE: We reviewed epidemiological studies of soy intake and breast cancer
      among Japanese women. This report is one among a series of articles by our
      research group, which is evaluating the existing evidence concerning the
      association between health-related lifestyles and cancer. METHODS: Original data
      were obtained from MEDLINE searches using PubMed or from searches of the Ichushi
      database, complemented with manual searches. Evaluation of associations was based
      on the strength of evidence and the magnitude of association, together with
      biological plausibility. RESULTS: Five cohort studies and six case-control
      studies were identified. Among the cohort studies, two studies observed that
      total soy intake (in terms of total amounts of soy foods or soy isoflavones) was
      associated with a moderate (0.5 <= relative risk <= 0.67 with statistical
      significance) or strong (relative risk <= 0.5 with statistical significance) risk
      reduction of breast cancer in postmenopausal women. Among the case-control
      studies, two studies reported a weak (0.67 <= odds ratio <= 1.5 with statistical
      significance or 0.5 <= odds ratio <= 0.67 without statistical significance)
      inverse association between total soy intake and the risk of breast cancer. In
      the former, this association was observed in all women combined-premenopausal and
      postmenopausal women-but in the latter, the association was confined to
      postmenopausal women. The associations of intakes of individual soy foods with
      the risk of breast cancer were generally null. There is some evidence that
      supports the biological plausibility of a protective effect of isoflavones on
      breast cancer risk. CONCLUSIONS: We conclude that soy intake possibly decreases
      the risk of breast cancer among Japanese women.

PMID- 24453273
TI  - XRCC3 polymorphisms are associated with the risk of developing radiation-induced
      late xerostomia in nasopharyngeal carcinoma patients treated with intensity
      modulation radiated therapy.
AB  - OBJECTIVE: The incidence of radiation-induced late xerostomia varies greatly in
      nasopharyngeal carcinoma patients treated with radiotherapy. The single
      nucleotide polymorphisms in genes involved in DNA repair and fibroblast
      proliferation may be correlated with such variability. The purpose of this paper
      was to evaluate the association between the risk of developing radiation-induced
      late xerostomia and four genetic polymorphisms: TGFbeta1 C-509T, TGFbeta1 T869C,
      XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with
      Intensity Modulation Radiated Therapy. METHODS: The severity of late xerostomia
      was assessed using a patient self-reported validated xerostomia questionnaire.
      Polymerase chain reaction-ligation detection reaction methods were performed to
      determine individual genetic polymorphism. The development of radiation-induced
      xerostomia associated with genetic polymorphisms was modeled using Cox
      proportional hazards, accounting for equivalent uniform dose. RESULTS: A total of
      43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox
      proportional hazard analyses showed a higher risk of late xerostomia for patients
      with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and
      dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for
      higher risk of late xerostomia. CONCLUSIONS: To our knowledge, this is the first
      study that demonstrated an association between genetic polymorphisms and the risk
      of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated
      with Intensity Modulation Radiated Therapy. Our findings suggest that the
      polymorphisms in XRCC3 are significantly associated with the risk of developing
      radiation-induced late xerostomia.

PMID- 24453274
TI  - Effect of the weekly administration of liposome-Paclitaxel combined with s-1 on
      advanced gastric cancer.
AB  - OBJECTIVE: This study is aimed to assess the efficacy and toxicity of weekly
      liposome-paclitaxel and S-1 combination therapy as first-line treatment for
      advanced gastric cancer. METHODS: The chemotherapy regime was 80 mg/m(2) liposome
      paclitaxel given on days 1, 8, 15 and 22, combined with S-1 60 mg (body surface
      area > 1.5) or 50 mg (1.25 < body surface area < 1.5) twice a day on days 1-28, 6
      weeks as one cycle. The patients continued to be treated until they received four
      cycles or until they developed either progressive disease or untolerated
      toxicity. The response rate, progression-free survival, overall survival and
      toxicity were evaluated. RESULTS: A total of 56 patients were enrolled, and the
      median age was 60 years (range = 38-70 years; 39 males and 17 females). The
      response rate and disease control rate were 25% (14/56) and 87.5% (49/56),
      respectively. The median progression-free survival was 6.1 months (95% confidence
      interval: 5.0-7.2), and the median overall survival was 10.6 months (95%
      confidence interval: 7.2-14.0). The most frequent hematological toxicities were
      neutropenia and anemia, which occurred in 22 (48.9%) and 11 (19.6%) patients,
      respectively. CONCLUSIONS: The weekly administration of a combined regimen of
      liposome-paclitaxel plus S-1 is effective and has a favorable toxicity profile
      for advanced gastric cancer.

PMID- 24453275
TI  - High-mobility group box-1 and its role in angiogenesis.
AB  - HMGB1 is an architectural chromatin-binding protein that can be released actively
      by activated cells or passively by dying cells and can serve as a DAMP molecule
      to drive the pathogenesis of inflammatory and angiogenic diseases. Through TLR4
      and RAGE signaling pathways, HMGB1 could regulate vascular growth in vivo and in
      vitro through diverse mechanisms, including induction of proangiogenic cytokine
      release and activation of ECs, macrophages, EPCs, and mesoangioblasts, all of
      which could contribute to vessel formation. Accordingly, HMGB1 plays a
      significant role in many angiogenesis-related conditions, such as tumors, PDR,
      wound-healing, and ischemia-induced angiogenesis. In this review, we focus on the
      regulatory role of HMGB1 in angiogenesis and recent progress in therapeutic
      strategies targeting HMGB1. 

PMID- 24453276
TI  - Stem cell factor induces AP-1-dependent mast cell IL-6 production via MAPK kinase
      3 activity.
AB  - Mast cells are critical immune effectors abundant in tissues interfacing with the
      environment and have major roles in allergen-induced inflammation and host
      responses to infection. SCF is a regulator of mast cell function and growth.
      However, the critical mechanisms in SCF-directed events remain incompletely
      defined. Here, we have investigated the role of MKK3 in mast cell SCF signaling
      dependent functions by using BMMCs from MKK3-deficient mice. MKK3 was
      phosphorylated rapidly and persistently following SCF-induced activation and
      contributed to mast cell proliferation but not survival or migration in response
      to SCF. Analysis of SCF-induced mast cell mediator secretion demonstrated that IL
      6 production is specifically dependent on MKK3 signals, both independently and in
      concert with IgE. Analysis of SCF-induced signaling showed that sustained p38
      phosphorylation was impaired in MKK3-deficient mast cells, where as early JNK and
      IkappaBalpha activation were enhanced. Notably, SCF-inducible expression and
      activation of c-Jun, a component of the AP-1 transcription factor, was
      significantly dependent on MKK3. Accordingly, AP-1 DNA-binding activity and
      interaction with the IL6 gene promoter was markedly impaired in MKK3-deficient
      mast cells, whereas transcription factors of the Egr family, NF-kappaB, and NFAT
      retained near-full activity. These results designate MKK3 as a novel, positive
      regulator of SCF-induced mast cell proliferation and a critical signaling protein
      for AP-1-dependent IL-6 production.

PMID- 24453277
TI  - High-frequency electrical stimulation of the human skin induces heterotopical
      mechanical hyperalgesia, heat hyperalgesia, and enhanced responses to
      nonnociceptive vibrotactile input.
AB  - High-frequency electrical stimulation (HFS) of the human skin induces increased
      pain sensitivity in the surrounding unconditioned skin. The aim of the present
      study was to characterize the relative contribution of the different types of
      nociceptive and nonnociceptive afferents to the heterotopical hyperalgesia
      induced by HFS. In 17 healthy volunteers (9 men and 8 women), we applied HFS to
      the ventral forearm. The intensity of perception and event-related brain
      potentials (ERPs) elicited by vibrotactile stimuli exclusively activating
      nonnociceptive low-threshold mechanoreceptors and thermonociceptive stimuli
      exclusively activating heat-sensitive nociceptive afferents were recorded before
      and after HFS. The previously described mechanical hyperalgesia following HFS was
      confirmed by measuring the changes in the intensity of perception elicited by
      mechanical punctate stimuli. HFS increased the perceived intensity of both
      mechanical punctate and thermonociceptive stimuli applied to the surrounding
      unconditioned skin. The time course of the effect of HFS on the perception of
      mechanical and thermal nociceptive stimuli was similar. This indicates that HFS
      does not only induce mechanical hyperalgesia, but also induces heat hyperalgesia
      in the heterotopical area. Vibrotactile ERPs were also enhanced after HFS,
      indicating that nonnociceptive somatosensory input could contribute to the
      enhanced responses to mechanical pinprick stimuli. Finally, the magnitude of
      thermonociceptive ERPs was unaffected by HFS, indicating that type II A-fiber
      mechano-heat nociceptors, thought to be the primary contributor to these brain
      responses, do not significantly contribute to the observed heat hyperalgesia. 

PMID- 24453278
TI  - Intracortical microstimulation of supplementary eye field impairs ability of
      monkeys to make serially ordered saccades.
AB  - Neurons in the supplementary eye field (SEF) of the macaque monkey exhibit rank
      selectivity, firing differentially as a function of the phase attained during the
      performance of a task requiring the execution of saccades to a series of objects
      in fixed order. The activity of these neurons is commonly thought to represent
      ordinal position in the service of serial-order performance. However, there is
      little evidence causally linking neuronal activity in the SEF to sequential
      behavior. To explore the role of the SEF in serial-order performance, we
      delivered intracortical microstimulation while monkeys performed a task requiring
      them to make saccades to three objects in a fixed order on each trial.
      Microstimulation, considered on average across all SEF sites and all phases of
      the trial, affected saccadic kinematics. In particular, it prolonged the reaction
      time, increased the peak velocity, and slightly increased the amplitude of
      saccades. In addition, it interfered with the monkeys' ability to select the
      target appropriate to a given phase of the trial. The pattern of the errors was
      such as would be expected if microstimulation shifted the neural representation
      of ordinal position toward a later phase of the trial. 

PMID- 24453279
TI  - Reorganization of muscle synergies during multidirectional reaching in the
      horizontal plane with experimental muscle pain.
AB  - Muscle pain induces a complex reorganization of the motor strategy which cannot
      be fully explained by current theories. We tested the hypothesis that the neural
      control of muscles during reaching in the presence of nociceptive input is
      determined by a reorganization of muscle synergies with respect to control
      conditions. Muscle pain was induced by injection of hypertonic saline into the
      anterior deltoid muscle of eight men. Electromyographic (EMG) signals were
      recorded from 12 upper limb muscles as subjects performed a reaching task before
      (baseline) and after the injection of hypertonic (pain) saline, and after the
      pain sensation vanished. The EMG envelopes were factorized in muscle synergies,
      and activation signals extracted for each condition. Nociceptive stimulation
      resulted in a complex muscle reorganization without changes in the kinematic
      output. The anterior deltoid muscle activity decreased in all subjects while the
      changes in other muscles were subject specific. Three synergies sufficed to
      describe the EMG patterns in each condition, suggesting that reaching movements
      remain modular in the presence of experimental pain. Muscle reorganization in all
      subjects was accompanied by a change in the activation signals compatible with a
      change in the central drive to muscles. One, two or three synergies were shared
      between the baseline and painful conditions, depending on the subject. These
      results indicate that nociceptive stimulation may induce a reorganization of
      modular control in reaching. We speculate that such reorganization may be due to
      the recruitment of synergies specific to the painful condition. 

PMID- 24453280
TI  - Polycystic liver disease presenting as acute abdomen.

PMID- 24453281
TI  - Limits on use of health economic assessments for rare diseases.
AB  - Funding of expensive treatments for rare (orphan) diseases is contentious. These
      agents fare poorly on 'efficiency' or health economic measures, such as the
      quality-adjusted life years, because of high cost and frequently poor gains in
      quality of life and survival. We show that cost-effectiveness assessments are
      flawed, and have only a limited role to play in reimbursement decisions for
      orphan drugs and beyond. 

PMID- 24453282
TI  - Vitamin D supplementation-clarity required regarding treatment regimens and
      target plasma levels.

PMID- 24453283
TI  - Vascular remodelling in the pathogenesis of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrosing
      interstitial pneumonia of unknown aetiology that usually leads to respiratory
      failure and death within 5 years of diagnosis. Alveolar epithelial cell injury,
      disruption of alveolar capillary membrane integrity and abnormal vascular repair
      and remodelling have all been proposed as possible pathogenic mechanisms. This
      review summarizes our current knowledge of the abnormalities in vascular
      remodelling observed in IPF and highlights several of the cytokines thought to
      play a pathogenic role, which may ultimately prove to be future therapeutic
      targets. 

PMID- 24453284
TI  - Gallstones increase the risk of developing renal stones: a nationwide population
      based retrospective cohort study.
AB  - BACKGROUND: This study identifies the effects of gall stone on the risks of
      developing renal stone in a nationwide cohort study. AIM: Studies on the
      association between gall stone and renal stone are scarce. METHODS: We identified
      patients with gallstones using the catastrophic illness registry of the Taiwan
      National Health Insurance Research Database (NHIRD). We selected a comparison
      cohort, random frequency-matched by age, sex and index year, from the general
      population. We analyzed the risk of renal stones by using Cox proportional
      hazards regression models for sex, age and comorbidities. RESULTS: Of the 23.74
      million people in the database, we followed 25 258 gallstone patients (54.5%
      female) and 101 029 control patients. The risk of developing renal stones was
      1.68-fold greater in gallstone patients, compared with patients without
      gallstones after adjusting for age, sex and comorbidities. The substantially
      increased risk of renal stones was also significant in gallstone patients
      regardless of comorbidities. In the follow-up period <1 year, the adjusted hazard
      ratio was 2.51 (95% CI = 2.25-2.80) compared to non-gallstone group. The
      cumulative incidence of renal stone in the gallstone group was higher than in the
      non-gallstone group (P < 0.0001, in the log-rank test). CONCLUSION: This
      nationwide cohort study demonstrates that the risk of renal stones is
      significantly higher in gallstone patients, compared with the general population.
      This study provides information to enable physicians to implement adequate
      prevention measures to decrease both stones formation.

PMID- 24453285
TI  - Sporadic lymphangioleiomyomatosis.

PMID- 24453286
TI  - Stem cells for liver regeneration.
AB  - The liver has a unique capacity to repair following injury, which is largely
      achieved by proliferation of hepatocytes. However, in situations of chronic or
      overwhelming liver injury, additional repair mechanisms, namely liver progenitor
      or oval cells, are activated. These cells, located in the canals of Hering,
      express markers for both hepatocytes and biliary cells and have the capacity to
      differentiate down both hepatocyte and biliary lineages. Previous work has
      suggested that the administration of autologous or allogeneic cell therapies such
      as haematopoietic or mesenchymal stem cells can augment liver repair by either
      stimulating endogenous repair mechanisms or by suppressing ongoing damage. A
      better understanding of how cell therapies can promote liver regeneration will
      lead to the refinement of these therapeutic approaches and also develop new
      pharmacological agents for liver repair.

PMID- 24453287
TI  - A work in progress: developing the new NCCN guidelines for survivorship.

PMID- 24453288
TI  - A patient with metastatic lung adenocarcinoma harboring concurrent EGFR L858R,
      EGFR germline T790M, and PIK3CA mutations: the challenge of interpreting results
      of comprehensive mutational testing in lung cancer.
AB  - Mutational testing has moved to the forefront as an integral component in the
      management of patients with non-small cell lung cancer (NSCLC). Currently 3
      targeted therapies (erlotinib, afatinib, and crizotinib) are approved by the FDA
      to treat patients with specific genetic abnormalities in NSCLC. As mutational
      screening expands to include a greater number of genes, the results will become
      more difficult to interpret, particularly if mutations are found in multiple
      genes or genes that are not actionable at the time of testing. This case report
      summarizes the diagnosis and treatment of a patient with NSCLC that harbored
      multiple potentially targetable driver mutations. It also discusses the current
      NCCN Clinical Practice Guidelines in Oncology for mutational testing in NSCLC and
      the inherent difficulties with interpreting mutational results when multiple
      mutations are found in a single gene or across multiple genes. 

PMID- 24453289
TI  - Brentuximab vedotin in patients with relapsed HIV-related lymphoma.
AB  - Lymphoma is a well-recognized complication in patients infected with HIV.
      Although its incidence has declined since the advent of antiretroviral therapy,
      it remains higher than seen in the general population. Several recent studies
      have noted improvement in clinical outcomes with the use of modern
      chemoimmunotherapy regimens. In patients who experience relapse, however, fewer
      data are available on the role of immunotherapy and its impact on outcomes. This
      case report presents 2 patients with relapsed HIV-associated lymphoma who
      experienced a second complete remission after treatment with the immunotherapy
      agent brentuximab vedotin. 

PMID- 24453290
TI  - Adolescent and young adult oncology, version 2.2014.
AB  - The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss
      the fertility and endocrine issues that are relevant to the management of AYA
      patients with cancer. Fertility preservation should be an essential part in the
      treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion
      of fertility preservation and contraception before the start of treatment.
      Oophoropexy and embryo cryopreservation are the 2 established options for
      fertility preservation in women. Semen cryopreservation before the start of
      treatment is the most reliable and well-established method of preserving
      fertility in men. AYA women with cancer also have unique contraception needs,
      depending on the type of cancer, its treatment, and treatment-related
      complications. Management of cancer during pregnancy poses significant diagnostic
      and therapeutic challenges for both the patient and the physician. AYA women
      diagnosed with cancer during pregnancy require individualized treatment from a
      multidisciplinary team involving medical, surgical, radiation, and gynecologic
      oncologists; obstetricians; and perinatologists. 

PMID- 24453291
TI  - Survivorship: introduction and definition. Clinical practice guidelines in
      oncology.
AB  - Many cancer survivors experience physical and/or psychosocial side effects, which
      can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for
      Survivorship provide screening, evaluation, and treatment recommendations for
      common consequences of cancer and cancer treatment for health care professionals
      who work with survivors of adult-onset cancer in the posttreatment period. These
      introductory sections of the guidelines include the panel's definition of cancer
      survivors, a discussion of the effects of cancer and its treatment, general
      principles and standards for survivorship care, and guidance regarding screening
      for problems that require further assessment. 

PMID- 24453293
TI  - The prostate cancer risk stratification project: database construction and risk
      stratification outcome analysis.
AB  - This investigation reports on the biochemical and clinical outcomes of a newly
      created pan-Canadian Prostate Cancer Risk Stratification (ProCaRS) database
      developed by the Genitourinary Radiation Oncologists of Canada (GUROC). GUROC
      ProCaRS template-compliant data on 7974 patients who underwent radiotherapy were
      received from 7 unique databases. Descriptive analysis, Cox proportional hazards,
      and Kaplan-Meier analyses were performed using American Society for Radiation
      Oncology (ASTRO) biochemical failure-free survival (BFFS), prostate cancer
      specific survival, and overall survival. Multivariable modeling for the primary
      ASTRO BFFS end point showed that age, prostate-specific antigen, T stage, and
      Gleason score and components such as hormonal therapy, and radiation treatment
      (brachytherapy with better outcome than external-beam) were predictive of
      outcome. Kaplan-Meier analysis of the existing GUROC and new NCCN classification
      system both showed good separation of all clinical outcome curves. The
      construction of a pan-Canadian database has informed important prostate cancer
      radiotherapy outcomes and risk stratification. 

PMID- 24453292
TI  - Baseline hemoglobin-A1c impacts clinical outcomes in patients with pancreatic
      cancer.
AB  - An association between diabetes mellitus and pancreatic ductal adenocarcinoma
      (PDA) has long been recognized. This article assesses the effect of the baseline
      hemoglobin-A1c (HbA1c) value on the clinical outcomes of patients with PDA. HbA1c
      values were prospectively collected on 656 consecutive patients presenting to a
      pancreas multidisciplinary cancer clinic from 2009 to 2012. Patients were
      diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable
      (R), borderline/locally advanced (BL), or metastatic (M) PDA. Excluded were those
      with prior treatment for PDA or a history of chronic diabetes mellitus (>1-year
      or unknown duration), resulting in a final cohort of 284 patients. Of 284
      patients, 44 had benign disease, 62 had R-PDA, 115 had BL-PDA, and 63 had M-PDA.
      Patients with malignant disease (R-, BL-, and M-PDA) collectively had a higher
      average HbA1c value than patients with BPD (6.1% vs 5.6%; P<.001). Among patients
      with PDA (n=240), HbA1c values of 6.5% or greater were significantly associated
      with inferior overall survival (OS) compared with patients with HbA1c values less
      than 6.5% (hazard ratio [HR], 1.74; OS, 10.2 vs 13.0 months; P=.007), along with
      other known prognostic factors, such as age of 65 years or older, ECOG
      performance status of 1 or greater, carbohydrate antigen 19-9 level greater than
      90, tumor size larger than 3 cm, and disease stage. HbA1c values of 6.5% or
      greater remained in the final predictive model using backward elimination (HR,
      1.46; P=.097), indicating that HbA1c values of 6.5% or greater influence OS of
      patients with PDA even when accounting for other known prognostic factors. HbA1c
      level at presentation is significantly higher in patients with PDA than patients
      with BPD and seems to affect survival. 

PMID- 24453294
TI  - Use and duration of chemotherapy in patients with metastatic breast cancer
      according to tumor subtype and line of therapy.
AB  - Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC).
      This article describes the impact of tumor subtype and the line of therapy on the
      duration of chemotherapy. Clinicopathologic characteristics were extracted from
      the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer
      Institute and analyzed according to subtype. Tumor subtypes were classified as
      hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast
      cancer. Duration of chemotherapy of each line was defined as the start of a
      chemotherapy regimen to the start of the next line of therapy as a result of
      progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and
      HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53
      years. Median overall survivals were 32 and 54 months for HER2-amplified disease,
      36 months for HR(+) breast cancer, and 17 months for TNBC (P<.0001). Patients
      with HER2-amplified disease received the most lines (median, 4; P=.032) and the
      longest duration of chemotherapy for every line. The median duration of
      chemotherapy in HER2-amplified patients remained at more than 4 months even out
      to sixth-line therapy. Patients with TNBC tended to receive the shortest duration
      of chemotherapy for every line of therapy. Tumor subtypes influence the number of
      lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2
      amplified disease who undergo chemotherapy beyond the third line, substantial
      rates of prolonged therapies suggest clinical benefit. The role of advanced
      (greater than third) chemotherapy lines in improving survival of all patients
      with MBC warrants further study. 

PMID- 24453295
TI  - Senior adult oncology, version 2.2014: clinical practice guidelines in oncology .
AB  - Cancer is the leading cause of death in older adults aged 60 to 79 years. The
      biology of certain cancers and responsiveness to therapy changes with the
      patient's age. Advanced age alone should not preclude the use of effective
      treatment that could improve quality of life or extend meaningful survival. The
      challenge of managing older patients with cancer is to assess whether the
      expected benefits of treatment are superior to the risk in a population with
      decreased life expectancy and decreased tolerance to stress. These guidelines
      provide an approach to decision-making in older cancer patients based on
      comprehensive geriatric assessment and also include disease specific issues
      related to age in the management of some cancer types in older adults.

PMID- 24453296
TI  - Hematopoietic stem cell transplantation for hematologic malignancies in older
      adults: geriatric principles in the transplant clinic.
AB  - Hematopoietic cell transplantation (HCT) provides a life-prolonging or
      potentially curative treatment option for patients with hematologic malignancies.
      Given the high transplant-related morbidity, these treatment strategies were
      initially restricted to younger patients, but are increasingly being used in
      older adults. The incidence of most hematologic malignancies increases with age;
      with the aging of the population, the number of potential older candidates for
      HCT increases. Autologous HCT (auto-HCT) in older patients may confer a slightly
      increased risk of specific toxicities (such as cardiac toxicities and mucositis)
      and have modestly lower effectiveness (in the case of lymphoma). However, auto
      HCT remains a feasible, safe, and effective therapy for selected older adults
      with multiple myeloma and lymphoma. Similarly, allogeneic transplant (allo-HCT)
      is a potential therapeutic option for selected older adults, although fewer data
      exist on allo-HCT in older patients. Based on currently available data, age alone
      is not the best predictor of toxicity and outcomes; rather, the comorbidities and
      functional status of the older patient are likely better predictors of toxicity
      than chronologic age in both the autologous and allogeneic setting. A
      comprehensive geriatric assessment (CGA) in older adults being considered for
      either an auto-HCT or allo-HCT may identify additional problems or geriatric
      syndromes, which may not be detected during the standard pretransplant
      evaluation. Further research is needed to establish the utility of CGA in
      predicting toxicity and to evaluate the quality of survival in older adults
      undergoing HCT. 

PMID- 24453298
TI  - Staying true to a mission: NCCN then and now.

PMID- 24453297
TI  - Assessing cognitive function and capacity in older adults with cancer.
AB  - The number of older individuals with cancer is increasing exponentially,
      mandating that oncologists contemplate more comprehensive and multidisciplinary
      approaches to treatment of this cohort. Recruitment of assessment instruments
      validated in older patients can be invaluable for guiding treatment and decision
      making by both patients and providers, and can arguably contribute to improving
      outcomes and health-related quality of life. The Comprehensive Geriatric
      Assessment is one such validated instrument that can be used by oncologists to
      assess patient readiness and appropriateness for prescribed cancer therapy. As a
      multidisciplinary diagnostic and treatment process, it comprises functional
      status, cognitive status, social support, and advance care preferences, and is an
      ideal instrument for evaluating complex older individuals. It is well established
      that many older individuals with cancer travel with multiple comorbid illnesses,
      including cognitive impairment, and when presented with a cancer diagnosis
      struggle to choose from multiple treatment options. In addition to the complete
      medical history, the ability of patients to decide on a course of therapy in
      concert with their oncologist is critically important. Alternatively, many
      oncologists are conflicted as to whether true informed consent for treatment can
      be obtained from many older patients. Having a roadmap to decision-making
      capacity is therefore an inescapable imperative in geriatric oncology, because
      careful attention must be directed at identifying older patients with cancer who
      might benefit from these assessments and the individualized treatment plans that
      emerge. 

PMID- 24453300
TI  - Neutrophil contribution in facilitating optic nerve regeneration.

PMID- 24453302
TI  - Ministrokes in channelrhodopsin-2 transgenic mice reveal widespread deficits in
      motor output despite maintenance of cortical neuronal excitability.
AB  - We evaluated the effects of ministrokes targeted to individual pial arterioles on
      motor function in Thy-1 line 18 channelrhodopsin-2 (ChR2) transgenic mice within
      the first hours after ischemia. Using optogenetics, we directly assessed both the
      excitability and motor output of cortical neurons in a manner independent of
      behavioral state or training. Occlusion of individual arterioles within the motor
      cortex led to a ministroke that was verified using laser speckle contrast
      imaging. Surprisingly, ministrokes targeted to a relatively small region of the
      forelimb motor map, with an ischemic core of 0.07 +/- 0.03 mm(2), impaired motor
      responses evoked from points across widespread areas of motor cortex even 1.5 mm
      away. Contrasting averaged ChR2-evoked electroencephalographic, spinal (ChR2
      evoked potential), and electromyographic responses revealed a mismatch between
      measures of cortical excitability and motor output within 60 min after stroke.
      This mismatch suggests that apparently excitable cortical neurons (even >1 mm
      into peri-infarct areas, away from the infarct core) were impaired in their
      capacity to generate spinal potentials leading to even more severe deficits in
      motor output at muscles. We suggest that ischemia, targeted to a subset of motor
      cortex, leads to relatively small reductions in excitability within motor cortex,
      and cumulative depression of both descending spinal circuits and motor output in
      response to the activation of widespread cortical territories even outside of the
      area directly affected by the ischemia. 

PMID- 24453301
TI  - Inhibitory plasticity dictates the sign of plasticity at excitatory synapses.
AB  - The broad connectivity of inhibitory interneurons and the capacity of inhibitory
      synapses to be plastic make them ideal regulators of the level of excitability of
      many neurons simultaneously. Whether inhibitory synaptic plasticity may also
      contribute to the selective regulation of single neurons and local microcircuits
      activity has not been investigated. Here we demonstrate that in rat primary
      visual cortex inhibitory synaptic plasticity is connection specific and depends
      on the activation of postsynaptic GABAB-Gi/o protein signaling. Through the
      activation of this intracellular signaling pathway, inhibitory plasticity can
      alter the state of a single postsynaptic neuron and directly affect the induction
      of plasticity at its glutamatergic inputs. This interaction is modulated by
      sensory experience. Our data demonstrate that in recurrent circuits, excitatory
      and inhibitory forms of synaptic plasticity are not integrated as independent
      events, but interact to cooperatively drive the activity-dependent rewiring of
      local microcircuits. 

PMID- 24453303
TI  - Rapid eye movement sleep and hippocampal theta oscillations precede seizure onset
      in the tetanus toxin model of temporal lobe epilepsy.
AB  - Improved understanding of the interaction between state of vigilance (SOV) and
      seizure onset has therapeutic potential. Six rats received injections of tetanus
      toxin (TeTX) in the ventral hippocampus that resulted in chronic spontaneous
      seizures. The distribution of SOV before 486 seizures was analyzed for a total of
      19 d of recording. Rapid eye movement sleep (REM) and exploratory wake, both of
      which express prominent hippocampal theta rhythm, preceded 47 and 34%, for a
      total of 81%, of all seizures. Nonrapid eye movement sleep (NREM) and
      nonexploratory wake, neither of which expresses prominent theta, preceded 6.8 and
      13% of seizures. We demonstrate that identification of SOV yields significant
      differentiation of seizure susceptibilities, with the instantaneous seizure rate
      during REM nearly 10 times higher than baseline and the rate for NREM less than
      half of baseline. Survival analysis indicated a shorter duration of preseizure
      REM bouts, with a maximum transition to seizure at ~90 s after the onset of REM.
      This study provides the first analysis of a correlation between SOV and seizure
      onset in the TeTX model of temporal lobe epilepsy, as well as the first
      demonstration that hippocampal theta rhythms associated with natural behavioral
      states can serve a seizure-promoting role. Our findings are in contrast with
      previous studies suggesting that the correlations between SOV and seizures are
      primarily governed by circadian oscillations and the notion that hippocampal
      theta rhythms inhibit seizures. The documentation of significant SOV-dependent
      seizure susceptibilities indicates the potential utility of SOV and its time
      course in seizure prediction and control. 

PMID- 24453304
TI  - Hippocampal pyramidal neurons switch from a multipolar migration mode to a novel
      "climbing" migration mode during development.
AB  - The hippocampus plays important roles in brain functions. Despite the importance
      of hippocampal functions, recent analyses of neuronal migration have mainly been
      performed on the cerebral neocortex, and the cellular mechanisms responsible for
      the formation of the hippocampus are not yet completely understood. Moreover, why
      a prolonged time is required for hippocampal neurons to complete their migration
      has been unexplainable for several decades. We analyzed the migratory profile of
      neurons in the developing mouse hippocampal CA1 region and found that the
      hippocampal pyramidal neurons generated near the ventricle became postmitotic
      multipolar cells and accumulated in the multipolar cell accumulation zone (MAZ)
      in the late stage of development. The hippocampal neurons passed through the
      pyramidal layer by a unique mode of migration. Their leading processes were
      highly branched and made contact with many radial fibers. Time-lapse imaging
      revealed that the migrating cells changed their scaffolds from the original
      radial fibers to other radial fibers, and as a result they proceed in a zigzag
      manner, with long intervals. The migrating cells in the hippocampus reminded us
      of "rock climbers" that instead of using their hands to pull up their bodies were
      using their leading processes to pull up their cell bodies. Because this mode of
      migration had never been described, we called it the "climbing" mode. The change
      from the "climbing" mode in the hippocampus to the "locomotion" mode in the
      neocortex may have contributed to the brain expansion during evolution. 

PMID- 24453305
TI  - A hierarchy of responses to auditory regularities in the macaque brain.
AB  - Can monkeys learn simple auditory sequences and detect when a new sequence
      deviates from the stored pattern? Here we tested the predictive-coding
      hypothesis, which postulates that cortical areas encode internal models of
      sensory sequences at multiple hierarchical levels, and use these predictive
      models to detect deviant stimuli. In humans, hierarchical predictive coding has
      been supported by studies of auditory sequence processing, but it is unclear
      whether internal hierarchical models of auditory sequences are also available to
      nonhuman animals. Using fMRI, we evaluated the encoding of auditory regularities
      in awake monkeys listening to first- and second-order sequence violations. We
      observed distinct fMRI responses to first-order violations in auditory cortex and
      to second-order violations in a frontoparietal network, a distinction only
      demonstrated in conscious humans so far. The results indicate that the capacity
      to represent and predict the structure of auditory sequences is shared by humans
      and nonhuman primates. 

PMID- 24453306
TI  - GABAergic neurogliaform cells represent local sources of insulin in the cerebral
      cortex.
AB  - Concentrations of insulin in the brain are severalfold higher than blood plasma
      levels. Insulin in the brain regulates the metabolism, molecular composition, and
      cognitive performance of microcircuits and reduces food intake; cerebral insulin
      levels are altered in diabetes, aging, obesity, and Alzheimer's disease. Released
      by pancreatic beta cells, insulin passes the blood-brain barrier, but sources of
      locally released insulin still remain unclear. We find that insulin is strongly
      expressed in GABAergic neurogliaform cells in the cerebral cortex of the rat
      detected by single-cell digital PCR. Focal application of glucose or
      glibenclamide to neurogliaform cells mimics the excitation suppressing effect of
      external insulin on local microcircuits via insulin receptors. Thus,
      neurogliaform cells might link GABAergic and insulinergic action in cortical
      microcircuits. 

PMID- 24453308
TI  - The electrogenic sodium bicarbonate cotransporter NBCe1 is a high-affinity
      bicarbonate carrier in cortical astrocytes.
AB  - The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is a robust
      regulator of intracellular H(+) and a significant base carrier in many cell
      types. Using wild-type (WT) and NBCe1-deficient (NBC-KO) mice, we have studied
      the role of NBCe1 in cortical astrocytes in culture and in situ by monitoring
      intracellular H(+) using the H(+)-sensitive dye BCECF [2',7'-bis-(carboxyethyl)-5
      (and-6)-carboxyfluorescein] in wide-field and confocal microscopy. Adding 0.1-3
      mm HCO3(-) to an O2-gassed, HEPES-buffered saline solution lowered the
      intracellular H(+) concentration with a Km of 0.65 mm HCO3(-) in WT astrocytes,
      but slowly raised [H(+)]i in NBCe1-KO astrocytes. Human NBCe1 heterologously
      expressed in Xenopus oocytes could be activated by adding 1-3 mm HCO3(-), and
      even by residual HCO3(-) in a nominally CO2/HCO3(-)-free saline solution. Our
      results demonstrate a surprisingly high apparent bicarbonate sensitivity mediated
      by NBCe1 in cortical astrocytes, suggesting that NBCe1 may operate over a wide
      bicarbonate concentration in these cells. 

PMID- 24453307
TI  - Prefrontal deficits in a murine model overexpressing the down syndrome candidate
      gene dyrk1a.
AB  - The gene Dyrk1a is the mammalian ortholog of Drosophila minibrain. Dyrk1a
      localizes in the Down syndrome (DS) critical region of chromosome 21q22.2 and is
      a major candidate for the behavioral and neuronal abnormalities associated with
      DS. PFC malfunctions are a common denominator in several neuropsychiatric
      diseases, including DS, but the contribution of DYRK1A in PFC dysfunctions, in
      particular the synaptic basis for impairments of executive functions reported in
      DS patients, remains obscure. We quantified synaptic plasticity, biochemical
      synaptic markers, and dendritic morphology of deep layer pyramidal PFC neurons in
      adult mBACtgDyrk1a transgenic mice that overexpress Dyrk1a under the control of
      its own regulatory sequences. We found that overexpression of Dyrk1a largely
      increased the number of spines on oblique dendrites of pyramidal neurons, as
      evidenced by augmented spine density, higher PSD95 protein levels, and larger
      miniature EPSCs. The dendritic alterations were associated with anomalous NMDAR
      mediated long-term potentiation and accompanied by a marked reduction in the
      pCaMKII/CaMKII ratio in mBACtgDyrk1a mice. Retrograde endocannabinoid-mediated
      long-term depression (eCB-LTD) was ablated in mBACtgDyrk1a mice. Administration
      of green tea extracts containing epigallocatechin 3-gallate, a potent DYRK1A
      inhibitor, to adult mBACtgDyrk1a mice normalized long-term potentiation and spine
      anomalies but not eCB-LTD. However, inhibition of the eCB deactivating enzyme
      monoacylglycerol lipase normalized eCB-LTD in mBACtgDyrk1a mice. These data shed
      light on previously undisclosed participation of DYRK1A in adult PFC dendritic
      structures and synaptic plasticity. Furthermore, they suggest its involvement in
      DS-related endophenotypes and identify new potential therapeutic strategies. 

PMID- 24453309
TI  - Decoding the dynamics of action, intention, and error detection for conscious and
      subliminal stimuli.
AB  - How do we detect our own errors, even before we receive any external feedback?
      One model hypothesizes that error detection results from the confrontation of two
      signals: a fast and unconscious motor code, based on a direct sensory-motor
      pathway; and a slower conscious intention code that computes the required
      response given the stimulus and task instructions. To test this theory and assess
      how the chain of cognitive processes leading to error detection is modulated by
      consciousness, we applied multivariate decoding methods to single-trial
      magnetoencephalography and electroencephalography data. Human participants
      performed a fast bimanual number comparison task on masked digits presented at
      threshold, such that about half of them remained unseen. By using both erroneous
      and correct trials, we designed orthogonal decoders for the actual response (left
      or right), the required response (left or right), and the response accuracy
      (correct or incorrect). While perceptual stimulus information and the actual
      response hand could be decoded on both conscious and non-conscious trials, the
      required response could only be decoded on conscious trials. Moreover, whether
      the current response was correct or incorrect could be decoded only when the
      target digits were conscious, at a time and with a certainty that varied with the
      amount of evidence in favor of the correct response. These results are in
      accordance with the proposed dual-route model of conscious versus nonconscious
      evidence accumulation, and suggest that explicit error detection is possible only
      when the brain computes a conscious representation of the desired response,
      distinct from the ongoing motor program. 

PMID- 24453312
TI  - Active dendrites regulate spectral selectivity in location-dependent spike
      initiation dynamics of hippocampal model neurons.
AB  - How does the presence of plastic active dendrites in a pyramidal neuron alter its
      spike initiation dynamics? To answer this question, we measured the spike
      triggered average (STA) from experimentally constrained, conductance-based
      hippocampal neuronal models of various morphological complexities. We transformed
      the STA computed from these models to the spectral and the spectrotemporal
      domains and found that the spike initiation dynamics exhibited temporally
      localized selectivity to a characteristic frequency. In the presence of the
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, the STA
      characteristic frequency strongly correlated with the subthreshold resonance
      frequency in the theta frequency range. Increases in HCN channel density or in
      input variance increased the STA characteristic frequency and its selectivity
      strength. In the absence of HCN channels, the STA exhibited weak delta frequency
      selectivity and the characteristic frequency was related to the repolarization
      dynamics of the action potentials and the recovery kinetics of sodium channels
      from inactivation. Comparison of STA obtained with inputs at various dendritic
      locations revealed that nonspiking and spiking dendrites increased and reduced
      the spectrotemporal integration window of the STA with increasing distance from
      the soma as direct consequences of passive filtering and dendritic spike
      initiation, respectively. Finally, the presence of HCN channels set the STA
      characteristic frequency in the theta range across the somatodendritic arbor and
      specific STA measurements were strongly related to equivalent transfer-impedance
      related measurements. Our results identify explicit roles for plastic active
      dendrites in neural coding and strongly recommend a dynamically reconfigurable
      multi-STA model to characterize location-dependent input feature selectivity in
      pyramidal neurons. 

PMID- 24453311
TI  - Active vision in marmosets: a model system for visual neuroscience.
AB  - The common marmoset (Callithrix jacchus), a small-bodied New World primate,
      offers several advantages to complement vision research in larger primates.
      Studies in the anesthetized marmoset have detailed the anatomy and physiology of
      their visual system (Rosa et al., 2009) while studies of auditory and vocal
      processing have established their utility for awake and behaving
      neurophysiological investigations (Lu et al., 2001a,b; Eliades and Wang, 2008a,b;
      Osmanski and Wang, 2011; Remington et al., 2012). However, a critical unknown is
      whether marmosets can perform visual tasks under head restraint. This has been
      essential for studies in macaques, enabling both accurate eye tracking and head
      stabilization for neurophysiology. In one set of experiments we compared the free
      viewing behavior of head-fixed marmosets to that of macaques, and found that
      their saccadic behavior is comparable across a number of saccade metrics and that
      saccades target similar regions of interest including faces. In a second set of
      experiments we applied behavioral conditioning techniques to determine whether
      the marmoset could control fixation for liquid reward. Two marmosets could fixate
      a central point and ignore peripheral flashing stimuli, as needed for receptive
      field mapping. Both marmosets also performed an orientation discrimination task,
      exhibiting a saturating psychometric function with reliable performance and
      shorter reaction times for easier discriminations. These data suggest that the
      marmoset is a viable model for studies of active vision and its underlying neural
      mechanisms. 

PMID- 24453310
TI  - Electroencephalography correlates of spatial working memory deficits in attention
      deficit/hyperactivity disorder: vigilance, encoding, and maintenance.
AB  - In the current study we sought to dissociate the component processes of working
      memory (WM) (vigilance, encoding and maintenance) that may be differentially
      impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected
      electroencephalographic (EEG) data from 52 children with ADHD and 47 typically
      developing (TD) children, ages 7-14 years, while they performed a spatial
      Sternberg working memory task. We used independent component analysis and time
      frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding
      processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes.
      We tested for effects of task difficulty and cue processing to evaluate
      vigilance. Children with ADHD showed attenuated alpha band event-related
      desynchronization (ERD) during encoding. This effect was more pronounced when
      task difficulty was low (consistent with impaired vigilance) and was predictive
      of memory task performance and symptom severity. Correlated with alpha ERD during
      encoding were alpha power increases during the maintenance period (relative to
      baseline), suggesting a compensatory effort. Consistent with this interpretation,
      midfrontal theta power increases during maintenance were stronger in ADHD and in
      high-load memory conditions. Furthermore, children with ADHD exhibited a
      maturational lag in development of posterior alpha power whereas age-related
      changes in frontal theta power deviated from the TD pattern. Last, subjects with
      ADHD showed age-independent attenuation of evoked responses to warning cues,
      suggesting low vigilance. Combined, these three EEG measures predicted diagnosis
      with 70% accuracy. We conclude that the interplay of impaired vigilance and
      encoding in ADHD may compromise maintenance and lead to impaired WM performance
      in this group. 

PMID- 24453313
TI  - Vigor of movements and the cost of time in decision making.
AB  - If we assume that the purpose of a movement is to acquire a rewarding state, the
      duration of the movement carries a cost because it delays acquisition of reward.
      For some people, passage of time carries a greater cost, as evidenced by how long
      they are willing to wait for a rewarding outcome. These steep discounters are
      considered impulsive. Is there a relationship between cost of time in decision
      making and cost of time in control of movements? Our theory predicts that people
      who are more impulsive should in general move faster than subjects who are less
      impulsive. To test our idea, we considered elementary voluntary movements:
      saccades of the eye. We found that in humans, saccadic vigor, assessed using
      velocity as a function of amplitude, was as much as 50% greater in one subject
      than another; that is, some people consistently moved their eyes with high vigor.
      We measured the cost of time in a decision-making task in which the same subjects
      were given a choice between smaller odds of success immediately and better odds
      if they waited. We measured how long they were willing to wait to obtain the
      better odds and how much they increased their wait period after they failed. We
      found that people that exhibited greater vigor in their movements tended to have
      a steep temporal discount function, as evidenced by their waiting patterns in the
      decision-making task. The cost of time may be shared between decision making and
      motor control. 

PMID- 24453314
TI  - Working memory load-dependent brain response predicts behavioral training gains
      in older adults.
AB  - In the domain of working memory (WM), a sigmoid-shaped relationship between WM
      load and brain activation patterns has been demonstrated in younger adults. It
      has been suggested that age-related alterations of this pattern are associated
      with changes in neural efficiency and capacity. At the same time, WM training
      studies have shown that some older adults are able to increase their WM
      performance through training. In this study, functional magnetic resonance
      imaging during an n-back WM task at different WM load levels was applied to
      compare blood oxygen level-dependent (BOLD) responses between younger and older
      participants and to predict gains in WM performance after a subsequent 12-session
      WM training procedure in older adults. We show that increased neural efficiency
      and capacity, as reflected by more "youth-like" brain response patterns in
      regions of interest of the frontoparietal WM network, were associated with better
      behavioral training outcome beyond the effects of age, sex, education, gray
      matter volume, and baseline WM performance. Furthermore, at low difficulty
      levels, decreases in BOLD response were found after WM training. Results indicate
      that both neural efficiency (i.e., decreased activation at comparable performance
      levels) and capacity (i.e., increasing activation with increasing WM load) of a
      WM-related network predict plasticity of the WM system, whereas WM training may
      specifically increase neural efficiency in older adults. 

PMID- 24453315
TI  - Dopamine-modulated recurrent corticoefferent feedback in primary sensory cortex
      promotes detection of behaviorally relevant stimuli.
AB  - Dopaminergic neurotransmission in primary auditory cortex (AI) has been shown to
      be involved in learning and memory functions. Moreover, dopaminergic projections
      and D1/D5 receptor distributions display a layer-dependent organization,
      suggesting specific functions in the cortical circuitry. However, the circuit
      effects of dopaminergic neurotransmission in sensory cortex and their possible
      roles in perception, learning, and memory are largely unknown. Here, we
      investigated layer-specific circuit effects of dopaminergic neuromodulation using
      current source density (CSD) analysis in AI of Mongolian gerbils. Pharmacological
      stimulation of D1/D5 receptors increased auditory-evoked synaptic currents in
      infragranular layers, prolonging local thalamocortical input via positive
      feedback between infragranular output and granular input. Subsequently, dopamine
      promoted sustained cortical activation by prolonged recruitment of long-range
      corticocortical networks. A detailed circuit analysis combining layer-specific
      intracortical microstimulation (ICMS), CSD analysis, and pharmacological cortical
      silencing revealed that cross-laminar feedback enhanced by dopamine relied on a
      positive, fast-acting recurrent corticoefferent loop, most likely relayed via
      local thalamic circuits. Behavioral signal detection analysis further showed that
      activation of corticoefferent output by infragranular ICMS, which mimicked
      auditory activation under dopaminergic influence, was most effective in eliciting
      a behaviorally detectable signal. Our results show that D1/D5-mediated
      dopaminergic modulation in sensory cortex regulates positive recurrent
      corticoefferent feedback, which enhances states of high, persistent activity in
      sensory cortex evoked by behaviorally relevant stimuli. In boosting horizontal
      network interactions, this potentially promotes the readout of task-related
      information from cortical synapses and improves behavioral stimulus detection. 

PMID- 24453316
TI  - Sensory cortical population dynamics uniquely track behavior across learning and
      extinction.
AB  - Neural responses in many cortical regions encode information relevant to
      behavior: information that necessarily changes as that behavior changes with
      learning. Although such responses are reasonably theorized to be related to
      behavior causation, the true nature of that relationship cannot be clarified by
      simple learning studies, which show primarily that responses change with
      experience. Neural activity that truly tracks behavior (as opposed to simply
      changing with experience) will not only change with learning but also change back
      when that learning is extinguished. Here, we directly probed for this pattern,
      recording the activity of ensembles of gustatory cortical single neurons as rats
      that normally consumed sucrose avidly were trained first to reject it (i.e.,
      conditioned taste aversion learning) and then to enjoy it again (i.e.,
      extinction), all within 49 h. Both learning and extinction altered cortical
      responses, consistent with the suggestion (based on indirect evidence) that
      extinction is a novel form of learning. But despite the fact that, as expected,
      postextinction single-neuron responses did not resemble "naive responses,"
      ensemble response dynamics changed with learning and reverted with extinction:
      both the speed of stimulus processing and the relationships among ensemble
      responses to the different stimuli tracked behavioral relevance. These data
      suggest that population coding is linked to behavior with a fidelity that single
      neuron coding is not. 

PMID- 24453317
TI  - Large-scale somatotopic refinement via functional synapse elimination in the
      sensory thalamus of developing mice.
AB  - Functional synapse elimination and strengthening are crucial developmental
      processes in the formation of precise neuronal circuits in the somatosensory
      system, but the underlying alterations in topographical organization are not yet
      fully understood. To address this issue, we generated transgenic mice in which
      afferent fibers originating from the whisker-related brain region, called the
      maxillary principal trigeminal nucleus (PrV2), were selectively visualized with
      genetically expressed fluorescent protein. We found that functional synapse
      elimination drove and established large-scale somatotopic refinement even after
      the thalamic barreloid architecture was formed. Before functional synapse
      elimination, the whisker sensory thalamus was innervated by afferent fibers not
      only from the PrV2, but also from the brainstem nuclei representing other body
      parts. Most notably, only afferent fibers from PrV2 onto a whisker sensory
      thalamic neuron selectively survived and were strengthened, whereas other
      afferent fibers were preferentially eliminated via their functional synapse
      elimination. This large-scale somatotopic refinement was at least partially
      dependent on somatosensory experience. These novel results uncovered a previously
      unrecognized role of developmental synapse elimination in the large-scale,
      instead of the fine-scale, somatotopic refinement even after the initial
      segregation of the barreloid map. 

PMID- 24453318
TI  - Reward-related activity in ventral striatum is action contingent and modulated by
      behavioral relevance.
AB  - Multiple features of the environment are often imbued with motivational
      significance, and the relative importance of these can change across contexts.
      The ability to flexibly adjust evaluative processes so that currently important
      features of the environment alone drive behavior is critical to adaptive
      routines. We know relatively little about the neural mechanisms involved,
      including whether motivationally significant features are obligatorily evaluated
      or whether current relevance gates access to value-sensitive regions. We
      addressed these questions using functional magnetic resonance imaging data and a
      task design where human subjects had to choose whether to accept or reject an
      offer indicated by visual and auditory stimuli. By manipulating, on a trial-by
      trial basis, which stimulus determined the value of the offer, we show choice
      activity in the ventral striatum solely reflects the value of the currently
      relevant stimulus, consistent with a model wherein behavioral relevance modulates
      the impact of sensory stimuli on value processing. Choice outcome signals in this
      same region covaried positively with wins on accept trials, and negatively with
      wins on reject trials, consistent with striatal activity at feedback reflecting
      correctness of response rather than reward processing per se. We conclude that
      ventral striatum activity during decision making is dynamically modulated by
      behavioral context, indexed here by task relevance and action selection. 

PMID- 24453319
TI  - Firing of hippocampal neurogliaform cells induces suppression of synaptic
      inhibition.
AB  - Little is known about how neuron firing recorded in vivo retrogradely influences
      synaptic strength. We injected the firing of a rat hippocampal neurogliaform cell
      (NGFC), a widely expressed GABAergic neuron type, detected in vivo during theta
      rhythm, into NGFCs of rat or neuronal nitric oxide synthase (nNOS)-Cre-tdTomato
      mouse recorded in vitro. We found that the "in vivo firing pattern" produced a
      transient firing-induced suppression of synaptic inhibition (FSI) evoked by a
      presynaptic NGFC. Imaging experiments demonstrate that FSI was associated with
      action potential backpropagation (bAP) and a supralinear increase in dendritic
      Ca(2+). The application of the L-type Ca(2+) channel antagonist nimodipine
      blocked FSI. Further pharmacological experiments, such as the application of a
      nitric oxide-sensitive guanylyl cyclase (NO-sGC) receptor antagonist, a NOS
      inhibitor, and NO donors, suggested that NO released from postsynaptic cells
      mediated FSI and likely activated presynaptic receptors to inhibit GABA release.
      The in vivo firing pattern modulated the size of unitary EPSPs impinging on NGFCs
      through FSI and not via a direct effect on excitatory synaptic transmission. Our
      data demonstrate: (1) retrograde signaling initiated by in vivo firing pattern,
      (2) interneuron bAPs detected with fast temporal resolution, and (3) a novel role
      for NO expressed by specific interneuron types. 

PMID- 24453320
TI  - The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by
      expression of mutant huntingtin, leading to defective cargo degradation.
AB  - Autophagy is an essential cellular pathway for degrading defective organelles and
      aggregated proteins. Defects in autophagy have been implicated in the
      neurodegenerative disorder Huntington's disease (HD), in which polyglutamine
      expanded huntingtin (polyQ-htt) is predominantly cleared by autophagy. In
      neurons, autophagosomes form constitutively at the axon tip and undergo robust
      retrograde axonal transport toward the cell body, but the factors regulating
      autophagosome dynamics and autophagosome maturation are not well understood.
      Here, we show that both huntingtin (htt) and its adaptor protein huntingtin
      associated protein-1 (HAP1) copurify and colocalize with autophagosomes in
      neurons. We use live-cell imaging and RNAi in primary neurons from GFP-LC3
      transgenic mice to show that htt and HAP1 control autophagosome dynamics,
      regulating dynein and kinesin motors to promote processive transport. Expression
      of polyQ-htt in either primary neurons or striatal cells from HD knock-in mice is
      sufficient to disrupt the axonal transport of autophagosomes. Htt is not required
      for autophagosome formation or cargo loading. However, the defective
      autophagosome transport observed in both htt-depleted neurons and polyQ-htt
      expressing neurons is correlated with inefficient degradation of engulfed
      mitochondrial fragments. Together, these studies identify htt and HAP1 as
      regulators of autophagosome transport in neurons and suggest that misregulation
      of autophagosome transport in HD leads to inefficient autophagosome maturation,
      potentially due to inhibition of autophagosome/lysosome fusion along the axon.
      The resulting defective clearance of both polyQ-htt aggregates and dysfunctional
      mitochondria by neuronal autophagosomes may contribute to neurodegeneration and
      cell death in HD. 

PMID- 24453321
TI  - Suboptimal use of neural information in a mammalian auditory system.
AB  - Establishing neural determinants of psychophysical performance requires both
      behavioral and neurophysiological metrics amenable to correlative analyses. It is
      often assumed that organisms use neural information optimally, such that any
      information available in a neural code that could improve behavioral performance
      is used. Studies have shown that detection of amplitude-modulated (AM) auditory
      tones by humans is correlated to neural synchrony thresholds, as recorded in
      rabbit at the level of the inferior colliculus, the first level of the ascending
      auditory pathway where neurons are tuned to AM stimuli. Behavioral thresholds in
      rabbit, however, are ~10 dB higher (i.e., 3 times less sensitive) than in humans,
      and are better correlated to rate-based than temporal coding schemes in the
      auditory midbrain. The behavioral and physiological results shown here illustrate
      an unexpected, suboptimal utilization of available neural information that could
      provide new insights into the mechanisms that link neuronal function to behavior.

PMID- 24453322
TI  - Short-term synaptic depression is topographically distributed in the cochlear
      nucleus of the chicken.
AB  - In the auditory system, sounds are processed in parallel frequency-tuned
      circuits, beginning in the cochlea. Activity of auditory nerve fibers reflects
      this frequency-specific topographic pattern, known as tonotopy, and imparts
      frequency tuning onto their postsynaptic target neurons in the cochlear nucleus.
      In birds, cochlear nucleus magnocellularis (NM) neurons encode the temporal
      properties of acoustic stimuli by "locking" discharges to a particular phase of
      the input signal. Physiological specializations exist in gradients corresponding
      to the tonotopic axis in NM that reflect the characteristic frequency (CF) of
      their auditory nerve fiber inputs. One feature of NM neurons that has not been
      investigated across the tonotopic axis is short-term synaptic plasticity. NM
      offers a rather homogeneous population of neurons with a distinct topographical
      distribution of synaptic properties that is ideal for the investigation of
      specialized synaptic plasticity. Here we demonstrate for the first time that
      short-term synaptic depression (STD) is expressed topographically, where unitary
      high CF synapses are more robust with repeated stimulation. Correspondingly, high
      CF synapses drive spiking more reliably than their low CF counterparts. We show
      that postsynaptic AMPA receptor desensitization does not contribute to the
      observed difference in STD. Further, rate of recovery from depression, a
      presynaptic property, does not differ tonotopically. Rather, we show that another
      presynaptic feature, readily releasable pool (RRP) size, is tonotopically
      distributed and inversely correlated with vesicle release probability.
      Mathematical model results demonstrate that these properties of vesicle dynamics
      are sufficient to explain the observed tonotopic distribution of STD. 

PMID- 24453323
TI  - Functional regulation of the SLC26-family protein prestin by calcium/calmodulin.
AB  - The solute carrier gene family 26 (SLC26) encodes membrane proteins with diverse
      physiological roles but with the common feature of halide involvement. Here, we
      present bioinformatic and biochemical evidence that SLC26 proteins have
      intrinsically disordered regions (IDRs) in their C-terminal domains and that
      these regions contain calmodulin (CaM) binding sites. The veracity of these
      predictions and the functional consequences of CaM binding were examined in
      prestin, SLC26A5, as a model for the SLC26 family and as one of the most
      investigated and best understood members. We found that CaM binds directly to the
      IDR in the C-terminal domain of prestin in a calcium-obligate manner. Using both
      isolated murine outer hair cells (OHCs) and a heterologous expression system, we
      also found that this calcium-obligate CaM binding shifts the operating point of
      the protein to more hyperpolarized potentials with consequent alteration of the
      function of the prestin. Because calcium is the main intracellular second
      messenger used by the efferent medial olivocochlear (MOC) pathway of the auditory
      system and CaM is abundant in OHCs, the CaM-prestin interaction may be involved
      in the MOC-mediated modulation of cochlear amplification. However, this
      regulatory mechanism is not likely to be restricted to cochlear OHCs, in light of
      both clear bioinformatic evidence and the fact that calcium and CaM are
      ubiquitous intracellular second messengers used by virtually all cell types.
      Hence, the calcium/CaM-dependent regulatory mechanism described herein is likely
      applicable to most, if not all, SLC26 paralogs. 

PMID- 24453325
TI  - Rapid dynamic changes of dendritic inhibition in the dentate gyrus by presynaptic
      activity patterns.
AB  - The dentate gyrus (DG) serves as a primary gate to control information transfer
      from the cortex to the hippocampus. Activation of incoming cortical inputs
      results in rapid synaptic excitation followed by slow GABA-mediated (GABAergic)
      synaptic inhibition onto DG granule cells (GCs). GABAergic inhibitory
      interneurons (INs) in the DG comprise fast-spiking (FS) and non-fast-spiking (non
      FS) cells. Anatomical analyses of DG INs reveal that FS cells are soma-targeting
      INs, whereas non-FS cells are dendrite-targeting INs. These two IN classes are
      differentially recruited by excitatory inputs and in turn provide exquisite
      spatiotemporal control over GC activity. Yet, little is known how FS and non-FS
      cells transform their presynaptic dynamics into varying postsynaptic response
      amplitudes. Using paired recordings in rat hippocampal slices, we show that
      inhibition in the DG is dominated by somatic GABAergic inputs during periods of
      sparse presynaptic activity, whereas dendritic GABAergic inputs are rapidly
      shifted to powerful and sustained inhibition during periods of intense
      presynaptic activity. The variant dynamics of dendritic inhibition is dependent
      on presynaptic IN subtypes and their activity patterns and is attributed to
      Ca(2+)-dependent increases in the probability of release and the size of the
      readily releasable pool. Furthermore, the degree of dynamic GABA release can be
      reduced by blocking voltage-gated K(+) channels, which increases the efficacy of
      dendrite-targeting IN output synapses during sparse firing. Such rapid dynamic
      modulation of dendritic inhibition may act as a frequency-dependent filter to
      prevent overexcitation of GC dendrites and thus set the excitatory-inhibitory
      synaptic balance in the DG circuits. 

PMID- 24453324
TI  - Expression of proteolipid protein gene in spinal cord stem cells and early
      oligodendrocyte progenitor cells is dispensable for normal cell migration and
      myelination.
AB  - Plp1 gene expression occurs very early in development, well before the onset of
      myelination, creating a conundrum with regard to the function of myelin
      proteolipid protein (PLP), one of the major proteins in compact myelin. Using PLP
      EGFP mice to investigate Plp1 promoter activity, we found that, at very early
      time points, PLP-EGFP was expressed in Sox2+ undifferentiated precursors in the
      spinal cord ventricular zone (VZ), as well as in the progenitors of both neuronal
      and glial lineages. As development progressed, most PLP-EGFP-expressing cells
      gave rise to oligodendrocyte progenitor cells (OPCs). The expression of PLP-EGFP
      in the spinal cord was quite dynamic during development. PLP-EGFP was highly
      expressed as cells delaminated from the VZ. Expression was downregulated as cells
      moved laterally through the cord, and then robustly upregulated as OPCs
      differentiated into mature myelinating oligodendrocytes. The presence of PLP-EGFP
      expression in OPCs raises the question of its role in this migratory population.
      We crossed PLP-EGFP reporter mice into a Plp1-null background to investigate the
      role of PLP in early OPC development. In the absence of PLP, normal numbers of
      OPCs were generated and their distribution throughout the spinal cord was
      unaffected. However, the orientation and length of OPC processes during migration
      was abnormal in Plp1-null mice, suggesting that PLP plays a role either in the
      structural integrity of OPC processes or in their response to extracellular cues
      that orient process outgrowth. 

PMID- 24453326
TI  - delta-opioid and dopaminergic processes in accumbens shell modulate the
      cholinergic control of predictive learning and choice.
AB  - Decision-making depends on the ability to extract predictive information from the
      environment to guide future actions. Outcome-specific Pavlovian-instrumental
      transfer (PIT) provides an animal model of this process in which a stimulus
      predicting a particular outcome biases choice toward actions earning that
      outcome. Recent evidence suggests that cellular adaptations of delta-opioid
      receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens
      shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in
      CINs critically influences D1-receptor (D1R)-expressing projection neurons in the
      NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling
      processes in dopamine D1- and D2-receptor-expressing neurons using drd2-eGFP
      mice, and found that PIT-related signaling was restricted to non-D2R-eGFP
      expressing neurons, suggesting major involvement of D1R-neurons. Next we
      confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but
      not the D2R antagonist raclopride, infused into the NAc-S abolished PIT in rats,
      an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH
      23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR
      agonists were found to sensitize the firing responses of CINs in brain slices
      prepared immediately after the PIT test. We confirmed the opioid
      acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic
      M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a
      treatment that rescued the deficit in PIT induced by naltrindole. We describe a
      model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons
      and stimulus-guided choice between goal-directed actions. 

PMID- 24453327
TI  - CLAC-P/collagen type XXV is required for the intramuscular innervation of
      motoneurons during neuromuscular development.
AB  - Formation of proper neuromuscular connections is a process coordinated by both
      motoneuron-intrinsic and target-dependent programs. Under these programs,
      motoneurons innervate target muscles, escape programmed cell death during fetal
      development, and form neuromuscular junctions (NMJ). Although a number of studies
      have revealed molecules involved in axon guidance to target muscles and NMJ
      formation, little is known about the molecular mechanisms linking intramuscular
      innervation and target-derived trophic factor-dependent prevention of motoneuron
      apoptosis. Here we studied the physiological function of CLAC-P/collagen XXV, a
      transmembrane-type collagen originally identified as a component of senile plaque
      amyloid of Alzheimer's disease brains, by means of generating Col25a1-deficient
      (KO) mice. Col25a1 KO mice died immediately after birth of respiratory failure.
      In Col25a1 KO mice, motor axons projected properly toward the target muscles but
      failed to elongate and branch within the muscle, followed by degeneration of
      axons. Failure of muscular innervation in Col25a1 KO mice led to excessive
      apoptosis during development, resulting in almost complete and exclusive loss of
      spinal motoneurons and immaturity in skeletal muscle development. Bax deletion in
      Col25a1 KO mice rescued motoneurons from apoptosis, although motor axons remained
      halted around the muscle entry site. Furthermore, these motoneurons were positive
      for phosphorylated c-Jun, an indicator of insufficient supply of target-derived
      survival signals. Together, these observations indicate that CLAC-P/collagen XXV
      is a novel essential factor that regulates the initial phase of intramuscular
      motor innervation, which is required for subsequent target-dependent motoneuron
      survival and NMJ formation during development. 

PMID- 24453328
TI  - Reward inference by primate prefrontal and striatal neurons.
AB  - The brain contains multiple yet distinct systems involved in reward prediction.
      To understand the nature of these processes, we recorded single-unit activity
      from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing
      a reward inference task using an asymmetric reward schedule. We found that
      neurons both in the LPFC and in the striatum predicted reward values for stimuli
      that had been previously well experienced with set reward quantities in the
      asymmetric reward task. Importantly, these LPFC neurons could predict the reward
      value of a stimulus using transitive inference even when the monkeys had not yet
      learned the stimulus-reward association directly; whereas these striatal neurons
      did not show such an ability. Nevertheless, because there were two set amounts of
      reward (large and small), the selected striatal neurons were able to exclusively
      infer the reward value (e.g., large) of one novel stimulus from a pair after
      directly experiencing the alternative stimulus with the other reward value (e.g.,
      small). Our results suggest that although neurons that predict reward value for
      old stimuli in the LPFC could also do so for new stimuli via transitive
      inference, those in the striatum could only predict reward for new stimuli via
      exclusive inference. Moreover, the striatum showed more complex functions than
      was surmised previously for model-free learning. 

PMID- 24453329
TI  - The limits of human stereopsis in space and time.
AB  - To encode binocular disparity, the visual system determines the image patches in
      one eye that yield the highest correlation with patches in the other eye. The
      computation of interocular correlation occurs after spatiotemporal filtering of
      monocular signals, which leads to restrictions on disparity variations that can
      support depth perception. We quantified those restrictions by measuring humans'
      ability to see disparity variation at a wide range of spatial and temporal
      frequencies. Lower-disparity thresholds cut off at very low spatiotemporal
      frequencies, which is consistent with the behavior of V1 neurons. Those
      thresholds are space-time separable, suggesting that the underlying neural
      mechanisms are separable. We also found that upper-disparity limits were
      characterized by a spatiotemporal, disparity-gradient limit; to be visible,
      disparity variation cannot exceed a fixed amount for a given interval in space
      time. Our results illustrate that the disparity variations that humans can see
      are very restricted compared with the corresponding luminance variations. The
      results also provide insight into the neural mechanisms underlying depth from
      disparity, such as why stimuli with long interocular delays can still yield clear
      depth percepts. 

PMID- 24453330
TI  - Propagation of epileptiform activity can be independent of synaptic transmission,
      gap junctions, or diffusion and is consistent with electrical field transmission.
AB  - The propagation of activity in neural tissue is generally associated with
      synaptic transmission, but epileptiform activity in the hippocampus can propagate
      with or without synaptic transmission at a speed of ~0.1 m/s. This suggests an
      underlying common nonsynaptic mechanism for propagation. To study this mechanism,
      we developed a novel unfolded hippocampus preparation, from CD1 mice of either
      sex, which preserves the transverse and longitudinal connections and recorded
      activity with a penetrating microelectrode array. Experiments using synaptic
      transmission and gap junction blockers indicated that longitudinal propagation is
      independent of chemical or electrical synaptic transmission. Propagation speeds
      of 0.1 m/s are not compatible with ionic diffusion or pure axonal conduction. The
      only other means of communication between neurons is through electric fields.
      Computer simulations revealed that activity can indeed propagate from cell to
      cell solely through field effects. These results point to an unexpected
      propagation mechanism for neural activity in the hippocampus involving endogenous
      field effect transmission. 

PMID- 24453331
TI  - Cell type-specific expression analysis to identify putative cellular mechanisms
      for neurogenetic disorders.
AB  - Recent advances have substantially increased the number of genes that are
      statistically associated with complex genetic disorders of the CNS such as autism
      and schizophrenia. It is now clear that there will likely be hundreds of distinct
      loci contributing to these disorders, underscoring a remarkable genetic
      heterogeneity. It is unclear whether this genetic heterogeneity indicates an
      equal heterogeneity of cellular mechanisms for these diseases. The commonality of
      symptoms across patients suggests there could be a functional convergence
      downstream of these loci upon a limited number of cell types or circuits that
      mediate the affected behaviors. One possible mechanism for this convergence would
      be the selective expression of at least a subset of these genes in the cell types
      that comprise these circuits. Using profiling data from mice and humans, we have
      developed and validated an approach, cell type-specific expression analysis, for
      identifying candidate cell populations likely to be disrupted across sets of
      patients with distinct genetic lesions. Using human genetics data and postmortem
      gene expression data, our approach can correctly identify the cell types for
      disorders of known cellular etiology, including narcolepsy and retinopathies.
      Applying this approach to autism, a disease where the cellular mechanism is
      unclear, indicates there may be multiple cellular routes to this disorder. Our
      approach may be useful for identifying common cellular mechanisms arising from
      distinct genetic lesions. 

PMID- 24453332
TI  - Functional reorganization of a prefrontal cortical network mediating
      consolidation of trace eyeblink conditioning.
AB  - The medial prefrontal cortex (mPFC) has been studied for its role in various
      cognitive functions, but the roles of its subregions remain unclear. We performed
      tetrode recordings simultaneously from prelimbic (PL) and rostral (rACC) and
      caudal (cACC) anterior cingulate subregions of the rabbit mPFC to understand
      their interactions during learning and tests of remote memory retention for
      whisker-signaled trace eyeblink conditioning. cACC neurons exhibited an innate
      response to the conditioning stimulus (CS) that rapidly decreased across
      sessions, suggesting an attentional role for facilitating CS-US associations.
      rACC neurons from conditioned rabbits exhibited robust responses to the CS that
      decreased within each session, possibly evaluating its emotional salience. PL
      neurons exhibited robust persistent activity during the trace interval during
      tests of remote memory retention, suggesting its involvement in retrieval and
      execution of a consolidated response. Mechanistically, conditioning was
      associated with a greater percentage of persistently responsive neurons than
      neurons from pseudoconditioned control rabbits, and responses differed
      significantly between trials with and without conditioned responses.
      Collectively, these responses reflect a functional reorganization of neural
      activity within the prefrontal network from an attentional mode to one that
      orchestrates the retrieval and execution of the learned response. 

PMID- 24453334
TI  - Cav2.1 channels control multivesicular release by relying on their distance from
      exocytotic Ca2+ sensors at rat cerebellar granule cells.
AB  - The concomitant release of multiple numbers of synaptic vesicles [multivesicular
      release (MVR)] in response to a single presynaptic action potential enhances the
      flexibility of synaptic transmission. However, the molecular mechanisms
      underlying MVR at a single CNS synapse remain unclear. Here, we show that the
      Cav2.1 subtype (P/Q-type) of the voltage-gated calcium channel is specifically
      responsible for the induction of MVR. In the rat cerebellar cortex, paired-pulse
      activation of granule cell (GC) ascending fibers leads not only to a facilitation
      of the peak amplitude (PPFamp) but also to a prolongation of the decay time
      (PPPdecay) of the EPSCs recorded from molecular layer interneurons. PPFamp is
      elicited by a transient increase in the number of released vesicles. PPPdecay is
      highly dependent on MVR and is caused by dual mechanisms: (1) a delayed release
      and (2) an extrasynaptic spillover of the GC transmitter glutamate and subsequent
      pooling of the glutamate among active synapses. PPPdecay was specifically
      suppressed by the Cav2.1 channel blocker omega-agatoxin IVA, while PPFamp
      responded to Cav2.2/Cav2.3 (N-type/R-type) channel blockers. The membrane
      permeable slow Ca(2+) chelator EGTA-AM profoundly reduced the decay time constant
      (taudecay) of the second EPSC; however, it only had a negligible impact on that
      of the first, thereby eliminating PPPdecay. These results suggest that the
      distance between presynaptic Cav2.1 channels and exocytotic Ca(2+) sensors is a
      key determinant of MVR. By transducing presynaptic action potential firings into
      unique Ca(2+) signals and vesicle release profiles, Cav2.1 channels contribute to
      the encoding and processing of neural information. 

PMID- 24453333
TI  - Differential neuronal targeting of a new and two known calcium channel beta4
      subunit splice variants correlates with their regulation of gene expression.
AB  - The beta subunits of voltage-gated calcium channels regulate surface expression
      and gating of CaV1 and CaV2 alpha1 subunits and thus contribute to neuronal
      excitability, neurotransmitter release, and calcium-induced gene regulation. In
      addition, certain beta subunits are targeted into the nucleus, where they
      interact directly with the epigenetic machinery. Whereas their involvement in
      this multitude of functions is reflected by a great molecular heterogeneity of
      beta isoforms derived from four genes and abundant alternative splicing, little
      is known about the roles of individual beta variants in specific neuronal
      functions. In the present study, an alternatively spliced beta4 subunit lacking
      the variable N terminus (beta4e) is identified. It is highly expressed in mouse
      cerebellum and cultured cerebellar granule cells (CGCs) and modulates P/Q-type
      calcium currents in tsA201 cells and CaV2.1 surface expression in neurons.
      Compared with the other two known full-length beta4 variants (beta4a and beta4b),
      beta4e is most abundantly expressed in the distal axon, but lacks nuclear
      targeting properties. To determine the importance of nuclear targeting of beta4
      subunits for transcriptional regulation, we performed whole-genome expression
      profiling of CGCs from lethargic (beta4-null) mice individually reconstituted
      with beta4a, beta4b, and beta4e. Notably, the number of genes regulated by each
      beta4 splice variant correlated with the rank order of their nuclear-targeting
      properties (beta4b > beta4a > beta4e). Together, these findings support isoform
      specific functions of beta4 splice variants in neurons, with beta4b playing a
      dual role in channel modulation and gene regulation, whereas the newly detected
      beta4e variant serves exclusively in calcium-channel-dependent functions. 

PMID- 24453335
TI  - Visual spatial attention has opposite effects on bidirectional plasticity in the
      human motor cortex.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are key mechanisms of
      synaptic plasticity that are thought to act in concert to shape neural
      connections. Here we investigated the influence of visual spatial attention on
      LTP-like and LTD-like plasticity in the human motor cortex. Plasticity was
      induced using paired associative stimulation (PAS), which involves repeated
      pairing of peripheral nerve stimulation and transcranial magnetic stimulation to
      alter functional responses in the thumb area of the primary motor cortex. PAS
      induced changes in cortical excitability were assessed using motor-evoked
      potentials. During plasticity induction, participants directed their attention to
      one of two visual stimulus streams located adjacent to each hand. When
      participants attended to visual stimuli located near the left thumb, which was
      targeted by PAS, LTP-like increases in excitability were significantly enhanced,
      and LTD-like decreases in excitability reduced, relative to when they attended
      instead to stimuli located near the right thumb. These differential effects on
      (bidirectional) LTP-like and LTD-like plasticity suggest that voluntary visual
      attention can exert an important influence on the functional organization of the
      motor cortex. Specifically, attention acts to both enhance the strengthening and
      suppress the weakening of neural connections representing events that fall within
      the focus of attention. 

PMID- 24453338
TI  - A novel function for Foxm1 in interkinetic nuclear migration in the developing
      telencephalon and anxiety-related behavior.
AB  - Interkinetic nuclear migration (INM) is a key feature of cortical neurogenesis.
      INM functions to maximize the output of the neuroepithelium, and more
      importantly, balance the self-renewal and differentiation of the progenitors.
      Although INM has been reported to be highly correlated with the cell cycle,
      little is known about the effects of cell cycle regulators on INM. In this study,
      by crossing Foxm1(fl/fl) mice with Emx1-Cre line, we report that a conditional
      disruption of forkhead transcription factor M1 (Foxm1) in dorsal telencephalon
      results in abnormal cell cycle progression, leading to impaired INM through the
      downregulation of Cyclin b1 and Cdc25b. The impairment of INM disturbs the
      synchronization of apical progenitors (APs) and promotes the transition from APs
      to basal progenitors (BPs) in a cell-autonomous fashion. Moreover, ablation of
      Foxm1 causes anxiety-related behaviors in adulthood. Thus, this study provides
      evidence of linkages among the cell cycle regulator Foxm1, INM, and adult
      behavior. 

PMID- 24453336
TI  - E2F1 coregulates cell cycle genes and chromatin components during the transition
      of oligodendrocyte progenitors from proliferation to differentiation.
AB  - Cell cycle exit is an obligatory step for the differentiation of oligodendrocyte
      progenitor cells (OPCs) into myelinating cells. A key regulator of the transition
      from proliferation to quiescence is the E2F/Rb pathway, whose activity is highly
      regulated in physiological conditions and deregulated in tumors. In this paper we
      report a lineage-specific decline of nuclear E2F1 during differentiation of
      rodent OPC into oligodendrocytes (OLs) in developing white matter tracts and in
      cultured cells. Using chromatin immunoprecipitation (ChIP) and deep-sequencing in
      mouse and rat OPCs, we identified cell cycle genes (i.e., Cdc2) and chromatin
      components (i.e., Hmgn1, Hmgn2), including those modulating DNA methylation
      (i.e., Uhrf1), as E2F1 targets. Binding of E2F1 to chromatin on the gene targets
      was validated and their expression assessed in developing white matter tracts and
      cultured OPCs. Increased expression of E2F1 gene targets was also detected in
      mouse gliomas (that were induced by retroviral transformation of OPCs) compared
      with normal brain. Together, these data identify E2F1 as a key transcription
      factor modulating the expression of chromatin components in OPC during the
      transition from proliferation to differentiation. 

PMID- 24453337
TI  - TREK2 expressed selectively in IB4-binding C-fiber nociceptors hyperpolarizes
      their membrane potentials and limits spontaneous pain.
AB  - Ongoing/spontaneous pain behavior is associated with ongoing/spontaneous firing
      (SF) in adult DRG C-fiber nociceptors (Djouhri et al., 2006). Causes of this SF
      are not understood. We show here that conducting (sometimes called uninjured) C
      nociceptors in neuropathic pain models with more hyperpolarized resting membrane
      potentials (Ems) have lower SF rates. Understanding the control of their Ems may
      therefore be important for limiting pathological pain. We report that TREK2, a
      leak K(+) channel, is selectively expressed in IB4 binding rat C-nociceptors.
      These IB4(+) C-neurons are ~10 mV more hyperpolarized than IB4(-) C-neurons in
      vivo (Fang et al., 2006). TREK2 knockdown by siRNA in these neurons in culture
      depolarized them by ~10 mV, suggesting that TREK2 is responsible for this ~10 mV
      difference. In vivo, more hyperpolarized C-nociceptor Ems were associated with
      higher cytoplasmic edge-TREK2 expression (edge-TREK2). Edge-TREK2 decreased in C
      neurons 7 d after axotomy, and their Ems depolarized by ~10 mV. This again
      supports a contribution of TREK2 to their Ems. These relationships between (1) Em
      and TREK2, (2) SF rate and Em, and (3) spontaneous pain behavior and C-nociceptor
      SF rate suggested that TREK2 knockdown might increase spontaneous pain. After CFA
      induced inflammation, spontaneous foot lifting (a measure of spontaneous pain)
      was (1) greater in rats with naturally lower TREK2 in ipsilateral small DRG
      neurons and (2) increased by siRNA-induced TREK2 knockdown in vivo. We conclude
      that TREK2 hyperpolarizes IB4 binding C-nociceptors and limits pathological
      spontaneous pain. Similar TREK2 distributions in small DRG neurons of several
      species suggest that these role(s) of TREK2 may be widespread. 

PMID- 24453339
TI  - Hemispheric asymmetry in auditory processing of speech envelope modulations in
      prereading children.
AB  - The temporal envelope of speech is an important cue contributing to speech
      intelligibility. Theories about the neural foundations of speech perception
      postulate that the left and right auditory cortices are functionally specialized
      in analyzing speech envelope information at different time scales: the right
      hemisphere is thought to be specialized in processing syllable rate modulations,
      whereas a bilateral or left hemispheric specialization is assumed for phoneme
      rate modulations. Recently, it has been found that this functional hemispheric
      asymmetry is different in individuals with language-related disorders such as
      dyslexia. Most studies were, however, performed in adults and school-aged
      children, and only a little is known about how neural auditory processing at
      these specific rates manifests and develops in very young children before reading
      acquisition. Yet, studying hemispheric specialization for processing syllable and
      phoneme rate modulations in preliterate children may reveal early neural markers
      for dyslexia. In the present study, human cortical evoked potentials to syllable
      and phoneme rate modulations were measured in 5-year-old children at high and low
      hereditary risk for dyslexia. The results demonstrate a right hemispheric
      preference for processing syllable rate modulations and a symmetric pattern for
      phoneme rate modulations, regardless of hereditary risk for dyslexia. These
      results suggest that, while hemispheric specialization for processing syllable
      rate modulations seems to be mature in prereading children, hemispheric
      specialization for phoneme rate modulation processing may still be developing.
      These findings could have important implications for the development of
      phonological and reading skills. 

PMID- 24453340
TI  - Involvement of Bcl-2-associated transcription factor 1 in the differentiation of
      early-born retinal cells.
AB  - Retinal progenitor proliferation and differentiation are tightly controlled by
      extrinsic cues and distinctive combinations of transcription factors leading to
      the generation of retinal cell type diversity. In this context, we have
      characterized Bcl-2-associated transcription factor (Bclaf1) during rodent
      retinogenesis. Bclaf1 expression is restricted to early-born cell types, such as
      ganglion, amacrine, and horizontal cells. Analysis of developing retinas in
      Bclaf1-deficient mice revealed a reduction in the numbers of retinal ganglion
      cells, amacrine cells and horizontal cells and an increase in the numbers of cone
      photoreceptor precursors. Silencing of Bclaf1expression by in vitro
      electroporation of shRNA in embryonic retina confirmed that Bclaf1 serves to
      promote amacrine and horizontal cell differentiation. Misexpression of Bclaf1 in
      late retinal progenitors was not sufficient to directly induce the generation of
      amacrine and horizontal cells. Domain deletion analysis indicated that the N
      terminal domain of Bclaf1 containing an arginine-serine-rich and a bZip domain is
      required for its effects on retinal cell differentiation. In addition, analysis
      revealed that Bclaf1 function occurs independently of its interaction with
      endogenous Bcl-2-related proteins. Altogether, our data demonstrates that
      Bclaf1expression in postmitotic early-born cells facilitates the differentiation
      of early retinal precursors into retinal ganglion cells, amacrine cells, and
      horizontal cells rather than into cone photoreceptors. 

PMID- 24453341
TI  - p140Cap regulates memory and synaptic plasticity through Src-mediated and citron
      N-mediated actin reorganization.
AB  - A major challenge in the neuroscience field is the identification of molecules
      and pathways that control synaptic plasticity and memory. Dendritic spines play a
      pivotal role in these processes, as the major sites of excitatory synapses in
      neuronal communication. Previous studies have shown that the scaffold protein
      p140Cap localizes into dendritic spines and that its knockdown negatively
      modulates spine shape in culture. However, so far, there is no information on its
      in vivo relevance. By using a knock-out mouse model, we here demonstrate that
      p140Cap is a key element for both learning and synaptic plasticity. Indeed,
      p140Cap(-/-) mice are impaired in object recognition test, as well as in LTP and
      in LTD measurements. The in vivo effects of p140Cap loss are presumably
      attenuated by noncell-autonomous events, since primary neurons obtained from
      p140Cap(-/-) mice show a strong reduction in number of mushroom spines and
      abnormal organization of synapse-associated F-actin. These phenotypes are most
      likely caused by a local reduction of the inhibitory control of RhoA and of
      cortactin toward the actin-depolymerizing factor cofilin. These events can be
      controlled by p140Cap through its capability to directly inhibit the activation
      of Src kinase and by its binding to the scaffold protein Citron-N. Altogether,
      our results provide new insight into how protein associated with dynamic
      microtubules may regulate spine actin organization through interaction with
      postsynaptic density components. 

PMID- 24453343
TI  - Measurement of population receptive fields in human early visual cortex using
      back-projection tomography.
AB  - Properties of human visual population receptive fields (pRFs) are currently
      estimated by performing measurements of visual stimulation using functional
      magnetic resonance imaging (fMRI), and then fitting the results using a
      predefined model shape for the pRF. Various models exist and different models may
      be appropriate under different circumstances, but the validity of the models has
      never been verified, suggesting the need for a model-free approach. Here, we
      demonstrate that pRFs can be directly reconstructed using a back-projection
      tomography approach that requires no a priori model. The back-projection method
      involves sweeping thin contrast-defined bars across the visual field whose
      orientation and direction is rotated through 0 degrees -180 degrees  in discrete
      increments. The measured fMRI time series within a cortical location can be
      approximated as a projection of the pRF along the long axis of the bar. The
      signals produced by a set of bar sweeps encircling the visual field form a
      sinogram. pRFs were reconstructed from these sinograms with a novel scheme that
      corrects for the blur introduced by the hemodynamic response and the stimulus-bar
      width. pRF positions agree well with the conventional model-based approach.
      Notably, a subset of the reconstructed pRFs shows significant asymmetry for both
      their excitatory and suppressive regions. Reconstructing pRFs using the
      tomographic approach is a fast, reliable, and accurate way to noninvasively
      estimate human pRF parameters and visual-field maps without the need for any a
      priori shape assumption. 

PMID- 24453342
TI  - Temporal windows in visual processing: "prestimulus brain state" and
      "poststimulus phase reset" segregate visual transients on different temporal
      scales.
AB  - Dynamic vision requires both stability of the current perceptual representation
      and sensitivity to the accumulation of sensory evidence over time. Here we study
      the electrophysiological signatures of this intricate balance between temporal
      segregation and integration in vision. Within a forward masking paradigm with
      short and long stimulus onset asynchronies (SOA), we manipulated the temporal
      overlap of the visual persistence of two successive transients. Human observers
      enumerated the items presented in the second target display as a measure of the
      informational capacity read-out from this partly temporally integrated visual
      percept. We observed higher beta-power immediately before mask display onset in
      incorrect trials, in which enumeration failed due to stronger integration of mask
      and target visual information. This effect was timescale specific, distinguishing
      between segregation and integration of visual transients that were distant in
      time (long SOA). Conversely, for short SOA trials, mask onset evoked a stronger
      visual response when mask and targets were correctly segregated in time.
      Examination of the target-related response profile revealed the importance of an
      evoked alpha-phase reset for the segregation of those rapid visual transients.
      Investigating this precise mapping of the temporal relationships of visual
      signals onto electrophysiological responses highlights how the stream of visual
      information is carved up into discrete temporal windows that mediate between
      segregated and integrated percepts. Fragmenting the stream of visual information
      provides a means to stabilize perceptual events within one instant in time. 

PMID- 24453344
TI  - On the relative detectability of configural properties.
AB  - A match-to-sample shape-discrimination task was employed to measure the
      detectability of different types of transformations. To create the foils for this
      task, the standard object could be altered by adding a small hole (a topological
      property), adding small bumps to straight edges (a projective property), changing
      the relative orientations of parallel contours (an affine property), or
      stretching the standard object to alter its aspect ratio (a Euclidean property).
      The results revealed that the relative perceptual salience of different types of
      shape change is consistent with the Klein hierarchy of geometries. That is to say
      observers were most sensitive to changes in topological structure, followed by
      changes in projective, affine, and Euclidean structure, respectively. The
      predicted patterns of performance among the different conditions were computed
      using a wide variety of commonly used shape-difference metrics, but none of them
      had a significant positive correlation with the observers' thresholds. 

PMID- 24453345
TI  - Simulating component-to-pattern dynamic effects with a computer model of middle
      temporal pattern neurons.
AB  - Some primate motion-sensitive middle temporal (MT) neurons respond best to motion
      orthogonal to a contour's orientation (component types) whereas another class
      (pattern type) responds maximally to the overall pattern motion. We have
      previously developed a model of the pattern-type neurons using integration of the
      activity generated in speed- and direction-tuned subunits. However, a number of
      other models have also been able to replicate MT neuron pattern-like behavior
      using a diverse range of mechanisms. This basic property does not really
      challenge or help discriminate between the different model types. There exist two
      sets of findings that we believe provide a better yardstick against which to
      assess MT pattern models. Some MT neurons have been shown to change from
      component to pattern behavior over brief time intervals. MT neurons have also
      been observed to switch from component- to pattern-like behavior when the
      intensity of the intersections in a plaid pattern stimulus changes. These
      properties suggest more complex time- and contrast-sensitive internal mechanisms
      underlying pattern motion extraction, which provide a real challenge for
      modelers. We have now replicated these two component-to-pattern effects using our
      MT pattern model. It incorporates two types of V1 neurons (sustained and
      transient), and these have slightly different time delays; this initially favors
      the component response, thus mimicking the temporal effects. We also discovered
      that some plaid stimuli contain a contrast asymmetry that depends on the plaid
      direction and the intensity of the intersections. This causes the model MT
      pattern units to act as component units. 

PMID- 24453346
TI  - Gaze behavior and the perception of egocentric distance.
AB  - The ground plane is thought to be an important reference for localizing objects,
      particularly when angular declination is informative, as it is for objects seen
      resting at floor level. A potential role for eye movements has been implicated by
      the idea that information about the nearby ground is required to localize objects
      more distant, and by the fact that the time course for the extraction of distance
      extends beyond the duration of a typical eye fixation. To test this potential
      role, eye movements were monitored when participants previewed targets. Distance
      estimates were provided by walking without vision to the remembered target
      location (blind walking) or by verbal report. We found that a strategy of holding
      the gaze steady on the object was as frequent as one where the region between the
      observer and object was fixated. There was no performance advantage associated
      with making eye movements in an observational study (Experiment 1) or when an eye
      movement strategy was manipulated experimentally (Experiment 2). Observers were
      extracting useful information covertly, however. In Experiments 3 through 5,
      obscuring the nearby ground plane had a modest impact on performance; obscuring
      the walls and ceiling was more detrimental. The results suggest that these
      alternate surfaces provide useful information when judging the distance to
      objects within indoor environments. Critically, they constrain the role for the
      nearby ground plane in theories of egocentric distance perception. 

PMID- 24453347
TI  - Visual crowding is anisotropic along the horizontal meridian during smooth
      pursuit.
AB  - Humans make smooth pursuit eye movements to foveate moving objects of interest.
      It is known that smooth pursuit alters visual processing, but there is currently
      no consensus on whether changes in vision are contingent on the direction the
      eyes are moving. We recently showed that visual crowding can be used as a
      sensitive measure of changes in visual processing, resulting from involvement of
      the saccadic eye movement system. The present paper extends these results by
      examining the effect of smooth pursuit eye movements on the spatial extent of
      visual crowding-the area over which visual stimuli are integrated. We found
      systematic changes in crowding that depended on the direction of pursuit and the
      distance of stimuli from the pursuit target. Relative to when no eye movement was
      made, the spatial extent of crowding increased for objects located contraversive
      to the direction of pursuit at an eccentricity of approximately 3 degrees . By
      contrast, crowding for objects located ipsiversive to the direction of pursuit
      remained unchanged. There was no change in crowding during smooth pursuit for
      objects located approximately 7 degrees  from the fovea. The increased size of
      the crowding zone for the contraversive direction may be related to the distance
      that the fovea lags behind the pursuit target during smooth eye movements.
      Overall, our results reveal that visual perception is altered dynamically
      according to the intended destination of oculomotor commands.

PMID- 24453348
TI  - Commentary: The critical role of measurement (and space elevators) in the study
      of child development.

PMID- 24453349
TI  - Let's get real about the regulation of TBC1D1 and TBC1D4 phosphorylation in
      skeletal muscle.

PMID- 24453350
TI  - Attenuated effects of exercise with an antioxidant supplement: too much of a good
      thing?

PMID- 24453351
TI  - Output vs. outcome: neurovascular transduction at rest.

PMID- 24453352
TI  - An introduction to the Bioscience Birthday Symposium held in honour of Ole
      Petersen CBE, FRS.

PMID- 24453353
TI  - Anatomy of arterial systems reveals that the major function of the heart is not
      to emit waves associated with the axial blood motion.

PMID- 24453354
TI  - Superior outcomes for military ankylosing spondylitis patients treated with anti
      TNF.
AB  - OBJECTIVES: The British military has a cohort of patients with ankylosing
      spondylitis (AS) characterised by young age and short disease duration. Many of
      the most severely affected AS patients have been treated since 2005 at Headley
      Court with anti-tumour necrosis factor (anti-TNF) therapy in accordance with
      National Institute of Health and Care Excellence guidance. We wanted to
      prospectively determine both the safety and efficacy of this new treatment in our
      British military population and compare this with relevant civilian study outcome
      data. METHODS: All AS patients commenced on anti-TNF therapy at Headley Court
      were prospectively monitored for treatment efficacy and side effects. Outcome
      measures used included the Bath Ankylosing Spondylitis Disease Activity Index.
      Our results were compared with a civilian comparison group (NHS) and relevant
      landmark clinical trial data. RESULTS: Our patients were younger (mean age 34.7
      years) and had a shorter duration (mean disease duration 6.9 years) than the
      civilian (NHS) comparison group. Our safety data were extremely benign with only
      two patients suffering minor side effects (local injection site reaction).
      Furthermore, our outcome data were superior to both NHS routine care and to
      landmark clinical studies. DISCUSSION: Prior to this study, there were no data on
      military AS populations receiving anti-TNF therapy. The study confirms British
      military patients tolerate this therapy extremely well and receive greater
      benefit from this treatment than that seen in any published study to date. We
      believe that this confirms that young age and short disease duration are good
      prognostic factors in the treatment of AS with anti-TNF therapy.

PMID- 24453355
TI  - Dosimetric study of a respiratory gating technique based on four-dimensional
      computed tomography in non-small-cell lung cancer.
AB  - This study sought to compare the differences in target volumes and dose
      distributions to the targets and organs at risk (OARs) between a four-dimensional
      computed tomography (4DCT)-based respiratory-gated intensity-modulated radiation
      therapy (IMRT) plan (PlanEOE) and a three-dimensional CT (3DCT)-based IMRT plan
      (Plan3D) in patients with non-small-cell lung cancer (NSCLC). For 17 patients
      with Stages I-III NSCLC, both 4DCT data and conventional 3DCT data were obtained.
      The Plan3D and PlanEOE were designed based on 3DCT data and 4DCT data,
      respectively. The displacements of the gross tumor volume (GTV) centroid were
      0.13 +/- 0.09 cm, 0.15 +/- 0.1 cm, and 0.27 +/- 0.27 cm in the right-left,
      anterior-posterior, and superior-inferior directions, respectively. The volume of
      the GTVEOE was 3.05 +/- 5.17 cm(3) larger than that of the GTV3D. The volume of
      the PTV3D was 72.82 +/- 48.65 cm(3) larger than that of the PTVEOE. There was no
      significant difference between the PTV3D and PTVEOE for V55.8, V60, V66 and the
      homogeneity index. The PTV3D had a lower target conformity index than the PTVEOE
      (P = 0.036). PlanEOE had a significantly lower lung V10, V20, V30, V40 and mean
      lung dose (MLD) than Plan3D. For the heart, PlanEOE had a significantly lower V30
      and mean dose. In conclusion, 4DCT is an appropriate method for assessing the
      displacement of the GTV centroid in three dimensions. PlanEOE has smaller PTVs
      and a decreased dose and volume for the normal lung and heart, as compared with
      Plan3D. 

PMID- 24453356
TI  - Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for patients
      with head and neck cancer: a systematic review.
AB  - There are two main enteral feeding strategies-namely nasogastric (NG) tube
      feeding and percutaneous gastrostomy-used to improve the nutritional status of
      patients with head and neck cancer (HNC). But up till now there has been no
      consistent evidence about which method of enteral feeding is the optimal method
      for this patient group. To compare the effectiveness of percutaneous gastrostomy
      and NGT feeding in patients with HNC, relevant literature was identified through
      Medline, Embase, Pubmed, Cochrane, Wiley and manual searches. We included
      randomized controlled trials (RCTs) and non-experimental studies comparing
      percutaneous gastrostomy-including percutaneous endoscopic gastrostomy (PEG) and
      percutaneous fluoroscopic gastrostomy (PFG) -with NG for HNC patients. Data
      extraction recorded characteristics of intervention, type of study and factors
      that contributed to the methodological quality of the individual studies. Data
      were then compared with respect to nutritional status, duration of feeding,
      complications, radiotherapy delays, disease-free survival and overall survival.
      Methodological quality of RCTs and non-experimental studies were assessed with
      separate standard grading scales. It became apparent from our studies that both
      feeding strategies have advantages and disadvantages. 

PMID- 24453357
TI  - Fifteen to twenty percent of HIV substitution mutations are associated with
      recombination.
AB  - HIV undergoes high rates of mutation and recombination during reverse
      transcription, but it is not known whether these events occur independently or
      are linked mechanistically. Here we used a system of silent marker mutations in
      HIV and a single round of infection in primary T lymphocytes combined with a high
      throughput sequencing and mathematical modeling approach to directly estimate the
      viral recombination and mutation rates. From >7 million nucleotides (nt) of
      sequences from HIV infection, we observed 4,801 recombination events and 859
      substitution mutations (~1.51 and 0.12 events per 1,000 nt, respectively). We
      used experimental controls to account for PCR-induced and transfection-induced
      recombination and sequencing error. We found that the single-cycle virus-induced
      mutation rate is 4.6 * 10(-5) mutations per nt after correction. By sorting of
      our data into recombined and nonrecombined sequences, we found a significantly
      higher mutation rate in recombined regions (P = 0.003 by Fisher's exact test). We
      used a permutation approach to eliminate a number of potential confounding
      factors and confirm that mutation occurs around the site of recombination and is
      not simply colocated in the genome. By comparing mutation rates in recombined and
      nonrecombined regions, we found that recombination-associated mutations account
      for 15 to 20% of all mutations occurring during reverse transcription. 

PMID- 24453358
TI  - Stability of the parainfluenza virus 5 genome revealed by deep sequencing of
      strains isolated from different hosts and following passage in cell culture.
AB  - The strain diversity of a rubulavirus, parainfluenza virus 5 (PIV5), was
      investigated by comparing 11 newly determined and 6 previously published genome
      sequences. These sequences represent 15 PIV5 strains, of which 6 were isolated
      from humans, 1 was from monkeys, 2 were from pigs, and 6 were from dogs. Strain
      diversity is remarkably low, regardless of host, year of isolation, or
      geographical origin; a total of 7.8% of nucleotides are variable, and the average
      pairwise difference between strains is 2.1%. Variation is distributed unevenly
      across the PIV5 genome, but no convincing evidence of selection for antibody
      mediated evasion in hemagglutinin-neuraminidase was found. The finding that some
      canine and porcine, but not primate, strains are mutated in the SH gene, and do
      not produce SH, raised the possibility that dogs (or pigs) may not be the natural
      host of PIV5. The genetic stability of PIV5 was also demonstrated during serial
      passage of one strain (W3) in Vero cells at a high multiplicity of infection,
      under conditions of competition with large proportions of defective interfering
      genomes. A similar observation was made for a strain W3 mutant (PIV5VDeltaC)
      lacking V gene function, in which the dominant changes were related to
      pseudoreversion in this gene. The mutations detected in PIV5VDeltaC during
      pseudoreversion, and also those characterizing the SH gene in canine and porcine
      strains, predominantly involved U-to-C transitions. This suggests an important
      role for biased hypermutation via an adenosine deaminase, RNA-specific (ADAR)
      like activity. IMPORTANCE: Here we report the sequence variation of 16 different
      isolates of parainfluenza virus 5 (PIV5) that were isolated from a number of
      species, including humans, monkeys, dogs, and pigs, over 4 decades. Surprisingly,
      strain diversity was remarkably low, regardless of host, year of isolation, or
      geographical origin. Variation was distributed unevenly across the PIV5 genome,
      but no convincing evidence of immune or host selection was found. This overall
      genome stability of PIV5 was also observed when the virus was grown in the
      laboratory, and the genome stayed remarkably constant even during the selection
      of virus mutants. Some of the canine isolates had lost their ability to encode
      one of the viral proteins, termed SH, suggesting that although PIV5 commonly
      infects dogs, dogs may not be the natural host for PIV5.

PMID- 24453359
TI  - Inefficient type I interferon-mediated antiviral protection of primary mouse
      neurons is associated with the lack of apolipoprotein l9 expression.
AB  - We examined the antiviral response promoted by type I interferons (IFN) in
      primary mouse neurons. IFN treatment of neuron cultures strongly upregulated the
      transcription of IFN-stimulated genes but conferred a surprisingly low resistance
      to infection by neurotropic viruses such as Theiler's murine encephalomyelitis
      virus (TMEV) or vesicular stomatitis virus (VSV). Response of primary mouse
      neurons to IFN treatment was heterogeneous, as many neurons failed to express the
      typical IFN response marker Mx1 after IFN treatment. This heterogeneous response
      of primary neurons correlated with a low level of basal expression of IFN
      stimulated genes, such as Stat1, that are involved in signal transduction of the
      IFN response. In addition, transcriptomic analysis identified 15 IFN-responsive
      genes whose expression was low in IFN-treated primary neurons compared to that of
      primary fibroblasts derived from the same mice (Dhx58, Gvin1, Sp100, Ifi203
      isoforms 1 and 2, Irgm2, Lgals3bp, Ifi205, Apol9b, Ifi204, Ifi202b, Tor3a, Slfn2,
      Ifi35, Lgals9). Among these genes, the gene coding for apolipoprotein L9b
      (Apol9b) displayed antiviral activity against Theiler's virus when overexpressed
      in L929 cells or in primary neurons. Accordingly, knocking down Apol9b expression
      in L929 cells increased viral replication. Therefore, we identified a new
      antiviral protein induced by interferon, ApoL9b, whose lack of expression in
      primary neurons likely contributes to the high sensitivity of these cells to
      viral infection. IMPORTANCE: The type I interferon (IFN) response is an innate
      immune defense mechanism that is critical to contain viral infection in the host
      until an adaptive immune response can be mounted. Neurons are a paradigm for
      postmitotic, highly differentiated cells. Our data show that primary mouse
      neurons that are exposed to type I interferon remain surprisingly susceptible to
      viral infection. On one hand, the low level of basal expression of some factors
      in neurons might prevent a rapid response of these cells. On the other hand, some
      genes that are typically activated by type I interferon in other cell types are
      expressed at much lower levels in neurons. Among these genes is the gene encoding
      apolipoprotein L9, a protein that proved to have antiviral activity against the
      neurotropic Theiler's murine encephalomyelitis virus. Our data suggest important
      functional differences in the IFN response mounted by specific cell populations.

PMID- 24453360
TI  - Biochemical and biological studies of mouse APOBEC3.
AB  - Many murine leukemia viruses (MLVs) are partially resistant to restriction by
      mouse APOBEC3 (mA3) and essentially fully resistant to induction of G-to-A
      mutations by mA3. In contrast, Vif-deficient HIV-1 (DeltaVif HIV-1) is profoundly
      restricted by mA3, and the restriction includes high levels of G-to-A mutation.
      Human APOBEC3G (hA3G), unlike mA3, is fully active against MLVs. We produced a
      glutathione S-transferase-mA3 fusion protein in insect cells and demonstrated
      that it possesses cytidine deaminase activity, as expected. This activity is
      localized within the N-terminal domain of this 2-domain protein; the C-terminal
      domain is enzymatically inactive but required for mA3 encapsidation into
      retrovirus particles. We found that a specific arginine residue and several
      aromatic residues, as well as the zinc-coordinating cysteines in the C-terminal
      domain, are necessary for mA3 packaging; a structural model of this domain
      suggests that these residues line a potential nucleic acid-binding interface.
      Mutation of a few potential phosphorylation sites in mA3 drastically reduces its
      antiviral activity by impairing either deaminase activity or its encapsidation.
      mA3 deaminates short single-stranded DNA oligonucleotides preferentially toward
      their 3' ends, whereas hA3G exhibits the opposite polarity. However, when
      packaged into infectious DeltaVif HIV-1 virions, both mA3 and hA3G preferentially
      induce deaminations toward the 5' end of minus-strand viral DNA, presumably
      because of the sequence of events during reverse transcription in vivo. Despite
      the fact that mA3 in MLV particles does not induce detectable deaminations upon
      infection, its deaminase activity is easily detected in virus lysates. We still
      do not understand how MLV resists mA3-induced G-to-A mutation. IMPORTANCE: One
      way that mammalian cells defend themselves against infection by retroviruses is
      with APOBEC3 proteins. These proteins convert cytidine bases to uridine bases in
      retroviral DNA. However, mouse APOBEC3 protein blocks infection by murine
      leukemia viruses without catalyzing this base change, and the mechanism of
      inhibition is not understood in this case. We have produced recombinant mouse
      APOBEC3 protein for the first time and characterized it here in a number of ways.
      Our mutational studies shed light on the mechanism by which mouse APOBEC3 protein
      is incorporated into retrovirus particles. While mouse APOBEC3 does not catalyze
      base changes in murine leukemia virus DNA, it can be recovered from these virus
      particles in enzymatically active form; it is still not clear why it fails to
      induce base changes when these viruses infect new cells.

PMID- 24453361
TI  - Blocking of exchange proteins directly activated by cAMP leads to reduced
      replication of Middle East respiratory syndrome coronavirus.
AB  - The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV)
      infections and diseases represents a potential threat for worldwide spread and
      requires development of effective therapeutic strategies. In this study, we
      revealed a novel positive function of an exchange protein directly activated by
      cyclic AMP 1 (cAMP-1; Epac-1) on MERS-CoV replication. Specifically, we have
      shown that Epac-specific inhibitor treatment or silencing Epac-1 gene expression
      rendered cells resistant to viral infection. We believe Epac-1 inhibitors deserve
      further study as potential therapeutic agents for MERS-CoV infection. 

PMID- 24453362
TI  - Association of herpes simplex virus pUL31 with capsid vertices and components of
      the capsid vertex-specific complex.
AB  - pU(L)34 and pU(L)31 of herpes simplex virus (HSV) comprise the nuclear egress
      complex (NEC) and are required for budding at the inner nuclear membrane. pU(L)31
      also associates with capsids, suggesting it bridges the capsid and pU(L)34 in the
      nuclear membrane to initiate budding. Previous studies showed that capsid
      association of pU(L)31 was precluded in the absence of the C terminus of pU(L)25,
      which along with pU(L)17 comprises the capsid vertex-specific complex, or CVSC.
      The present studies show that the final 20 amino acids of pU(L)25 are required
      for pU(L)31 capsid association. Unexpectedly, in the complete absence of pU(L)25,
      or when pU(L)25 capsid binding was precluded by deletion of its first 50 amino
      acids, pU(L)31 still associated with capsids. Under these conditions, pU(L)31 was
      shown to coimmunoprecipitate weakly with pU(L)17. Based on these data, we
      hypothesize that the final 20 amino acids of pU(L)25 are required for pU(L)31 to
      associate with capsids. In the absence of pU(L)25 from the capsid, regions of
      capsid-associated pU(L)17 are bound by pU(L)31. Immunogold electron microscopy
      revealed that pU(L)31 could associate with multiple sites on a single capsid in
      the nucleus of infected cells. Electron tomography revealed that immunogold
      particles specific to pU(L)31 protein bind to densities at the vertices of the
      capsid, a location consistent with that of the CVSC. These data suggest that
      pU(L)31 loads onto CVSCs in the nucleus to eventually bind pU(L)34 located within
      the nuclear membrane to initiate capsid budding. IMPORTANCE: This study is
      important because it localizes pU(L)1, a component previously known to be
      required for HSV capsids to bud through the inner nuclear membrane, to the vertex
      specific complex of HSV capsids, which comprises the unique long region 25
      (U(L)25) and U(L)17 gene products. It also shows this interaction is dependent on
      the C terminus of U(L)25. This information is vital for understanding how capsids
      bud through the inner nuclear membrane.

PMID- 24453363
TI  - Ribavirin-resistant variants of foot-and-mouth disease virus: the effect of
      restricted quasispecies diversity on viral virulence.
AB  - Mutagenic nucleoside analogues can be used to isolate RNA virus high-fidelity RNA
      dependent RNA polymerase (RdRp) variants, the majority of which are attenuated in
      vivo. However, attenuated foot-and-mouth disease virus (FMDV) high-fidelity RdRp
      variants have not been isolated, and the correlations between RdRp fidelity and
      virulence remain unclear. Here, the mutagen ribavirin was used to select a
      ribavirin-resistant population of FMDV, and 4 amino acid substitutions (D5N,
      A38V, M194I, and M296V) were identified in the RdRp-coding region of the
      population. Through single or combined mutagenesis using a reverse genetics
      system, we generated direct experimental evidence that the rescued D5N, A38V, and
      DAMM mutants but not the M194I and M296V mutants are high-fidelity RdRp variants.
      Mutagen resistance assays revealed that the higher replication fidelity was
      associated with higher-level resistance to ribavirin. In addition, significantly
      attenuated fitness and virulence phenotypes were observed for the D5N, A38V, and
      DAMM mutants. Based on a systematic quantitative analysis of fidelity and
      virulence, we concluded that higher replication fidelity is associated with a
      more attenuated virus. These data suggest that the resulting restricted
      quasispecies diversity compromises the adaptability and virulence of an RNA virus
      population. The modulation of replication fidelity to attenuate virulence may
      represent a general strategy for the rational design of new types of live,
      attenuated vaccine strains. IMPORTANCE: The ribavirin-isolated poliovirus (PV)
      RdRp G64S variant, the polymerases of which were of high replication fidelity,
      was attenuated in vivo. It has been proposed (M. Vignuzzi, E. Wendt, and R.
      Andino, Nat. Med. 14:154-161, http://dx.doi.org/10.1038/nm1726) that modulation
      of replication fidelity is a promising approach for engineering attenuated virus
      vaccines. The subsequently mutagen-isolated RdRp variants also expressed the high
      fidelity polymerase, but not all of them were attenuated. Few studies have shown
      the exact correlation between fidelity and virulence. The present study
      investigates the effect of restricted quasispecies diversity on viral virulence
      via several attenuated FMDV high-fidelity RdRp variants. Our findings may aid in
      the rational design of a new type of vaccine strain.

PMID- 24453364
TI  - Analysis of the Cullin binding sites of the E4orf6 proteins of human adenovirus
      E3 ubiquitin ligases.
AB  - E4orf6 proteins of human adenoviruses form Cullin-based E3 ubiquitin ligase
      complexes that degrade cellular proteins, which impedes efficient viral
      replication. These complexes also include the viral E1B55K product, which is
      believed to recruit most substrates for ubiquitination. Heterogeneity in the
      composition of these ligases exists, as serotypes representing some species form
      Cul5-based complexes (species B2, C, D, and E), whereas others utilize Cul2
      (species A and F). Adenovirus type 16 (Ad16; species B1) binds significant levels
      of both. In this report, we show that the Cul2 binding sequence in E4orf6 of Ad12
      (species A) and Ad40 (species F) resembles the cellular consensus Cul2 box.
      Mutation within this Cul2 box prevents binding not only of Cul2 but also in some
      cases Elongin C and reduces the ability to degrade target proteins, such as Mre11
      and p53. A comparable Cul2 box is not present in E4orf6 of Ad5 and other
      serotypes that bind Cul5; however, creation of this Cul2 box sequence in Ad5
      E4orf6 promoted binding to Cul2 and Cul2-dependent degradation of Mre11. E4orf6
      of Ad16 also binds Cul2; however, unlike Ad40, it does not contain an Ad12-like
      Cul2 box, suggesting that Ad16 binds Cul2 in a unique but perhaps nonfunctional
      manner, as only Cul5 binding complexes appeared able to degrade Mre11. Our
      extensive analyses have thus far failed to identify a consensus Cul5 binding
      sequence, suggesting that association occurs via a novel and perhaps complex
      pattern of protein-protein interactions. Nevertheless, the identification of the
      Cul2 box may allow prediction of Cullin specificity for all E4orf6-containing
      Adenoviridae. IMPORTANCE: The work described in this paper is a continuation of
      our in-depth studies on the Cullin-based E3 ligase complexes formed by the viral
      E4orf6 and E1B55K proteins of all human adenoviruses. This complex induces the
      degradation of a growing series of cellular proteins that impede efficient viral
      replication. Some human adenovirus species utilize Cul5, whereas others bind
      Cul2. In this paper, we are the first to identify the E4orf6 Cul2 binding site,
      which conforms in sequence to a classic cellular Cul2 box. Ours is the first
      detailed biochemical and genetic analysis of a Cul2-based adenovirus ligase and
      provides insights into both the cooperative interactions in forming Cullin-based
      ligases as well as the universality of formation of all adenovirus ligase
      complexes. Our work now permits future analysis of the evolutionary significance
      of the ligase complex, work that is currently in progress in our lab.

PMID- 24453365
TI  - Maintenance of large numbers of virus genomes in human cytomegalovirus-infected
      T98G glioblastoma cells.
AB  - After infection, human cytomegalovirus (HCMV) persists for life. Primary
      infections and reactivation of latent virus can both result in congenital
      infection, a leading cause of central nervous system birth defects. We previously
      reported long-term HCMV infection in the T98G glioblastoma cell line (1). HCMV
      infection has been further characterized in T98Gs, emphasizing the presence of
      HCMV DNA over an extended time frame. T98Gs were infected with either HCMV Towne
      or AD169-IE2-enhanced green fluorescent protein (eGFP) strains. Towne infections
      yielded mixed IE1 antigen-positive and -negative (Ag(+)/Ag(-)) populations. AD169
      IE2-eGFP infections also yielded mixed populations, which were sorted to obtain
      an IE2(-) (Ag(-)) population. Viral gene expression over the course of infection
      was determined by immunofluorescent analysis (IFA) and reverse transcription-PCR
      (RT-PCR). The presence of HCMV genomes was determined by PCR, nested PCR (n-PCR),
      and fluorescence in situ hybridization (FISH). Compared to the HCMV latency
      model, THP-1, Towne-infected T98Gs expressed IE1 and latency-associated
      transcripts for longer periods, contained many more HCMV genomes during early
      passages, and carried genomes for a greatly extended period of passaging. Large
      numbers of HCMV genomes were also found in purified Ag(-) AD169-infected cells
      for the first several passages. Interestingly, latency transcripts were observed
      from very early times in the Towne-infected cells, even when IE1 was expressed at
      low levels. Although AD169-infected Ag(-) cells expressed no detectable levels of
      either IE1 or latency transcripts, they also maintained large numbers of genomes
      within the cell nuclei for several passages. These results identify HCMV-infected
      T98Gs as an attractive new model in the study of the long-term maintenance of
      virus genomes in the context of neural cell types. IMPORTANCE: Our previous work
      showed that T98G glioblastoma cells were semipermissive to HCMV infection; virus
      trafficked to the nucleus, and yet only a proportion of cells stained positive
      for viral antigens, thus allowing continual subculturing and passaging. The cells
      eventually transitioned to a state where viral genomes were maintained without
      viral antigen expression or virion production. Here we report that during long
      term T98G infection, large numbers of genomes were maintained within all of the
      cells' nuclei for the first several passages (through passage 4 [P4]), even in
      the presence of continual cellular division. Surprisingly, genomes were
      maintained, albeit at a lower level, through day 41. This is decidedly longer
      than in any other latency model system that has been described to date. We
      believe that this system offers a useful model to aid in unraveling the cellular
      components involved in viral genome maintenance (and presumably replication) in
      cells carrying long-term latent genomes in a neural context.

PMID- 24453366
TI  - Novel vaccine regimen elicits strong airway immune responses and control of
      respiratory syncytial virus in nonhuman primates.
AB  - Induction of long-lasting immunity against viral respiratory tract infections
      remains an elusive goal. Using a nonhuman primate model of human respiratory
      syncytial virus (hRSV) infection, we compared mucosal and systemic immune
      responses induced by different DNA delivery approaches to a novel parenteral DNA
      prime-tonsillar adenoviral vector booster immunization regimen. Intramuscular
      (i.m.) electroporation (EP) of a DNA vaccine encoding the fusion protein of hRSV
      induced stronger systemic immune responses than intradermal EP, tattoo
      immunization, and conventional i.m. DNA injection. A single EP i.m., followed by
      two atraumatic tonsillar immunizations with the adenoviral vector, elicited
      strong systemic immune responses, an unique persistent CD4(+) and CD8(+) T cell
      response in the lower respiratory tract and protection from intranasal hRSV
      challenge. Thus, parenteral DNA priming followed by booster immunization targeted
      to a mucosal inductive site constitutes an effective vaccine regimen for
      eliciting protective immune responses at mucosal effector sites. IMPORTANCE: The
      human respiratory syncytial virus (hRSV) is the most common cause of severe
      respiratory tract disease in infancy and leads to substantial morbidity and
      morality in the elderly. In this study, we compared the immunogenicity and
      efficacy of several gene-based immunization protocols in rhesus macaques.
      Thereby, we found that the combination of an initially parenterally delivered DNA
      vaccine with a subsequent atraumatic tonsillar adenoviral vector immunization
      results in a strong systemic immune response accompanied by an exceptional high T
      cell response in the mucosa. Strikingly, these animals were protected against a
      RSV challenge infection controlling the viral replication indicated by a 1,000
      fold-lower viral load in the lower respiratory tract. Since mucosal cellular
      responses of this strength had not been described in earlier RSV vaccine studies,
      this heterologous DNA prime-tonsillar boost vaccine strategy is very promising
      and should be pursued for further preclinical and clinical testing.

PMID- 24453367
TI  - Efficacy and mechanism of a glycoside compound inhibiting abnormal prion protein
      formation in prion-infected cells: implications of interferon and
      phosphodiesterase 4D-interacting protein.
AB  - A new type of antiprion compound, Gly-9, was found to inhibit abnormal prion
      protein formation in prion-infected neuroblastoma cells, in a prion strain
      independent manner, when the cells were treated for more than 1 day. It reduced
      the intracellular prion protein level and significantly modified mRNA expression
      levels of genes of two types: interferon-stimulated genes were downregulated
      after more than 2 days of treatment, and the phosphodiesterase 4D-interacting
      protein gene, a gene involved in microtubule growth, was upregulated after more
      than 1 day of treatment. A supplement of interferon given to the cells partly
      restored the abnormal prion protein level but did not alter the normal prion
      protein level. This interferon action was independent of the Janus activated
      kinase-signal transducer and activator of transcription signaling pathway.
      Therefore, the changes in interferon-stimulated genes might be a secondary effect
      of Gly-9 treatment. However, gene knockdown of phosphodiesterase 4D-interacting
      protein restored or increased both the abnormal prion protein level and the
      normal prion protein level, without transcriptional alteration of the prion
      protein gene. It also altered the localization of abnormal prion protein
      accumulation in the cells, indicating that phosphodiesterase 4D-interacting
      protein might affect prion protein levels by altering the trafficking of prion
      protein-containing structures. Interferon and phosphodiesterase 4D-interacting
      protein had no direct mutual link, demonstrating that they regulate abnormal
      prion protein levels independently. Although the in vivo efficacy of Gly-9 was
      limited, the findings for Gly-9 provide insights into the regulation of abnormal
      prion protein in cells and suggest new targets for antiprion compounds.
      IMPORTANCE: This report describes our study of the efficacy and potential
      mechanism underlying the antiprion action of a new antiprion compound with a
      glycoside structure in prion-infected cells, as well as the efficacy of the
      compound in prion-infected animals. The study revealed involvements of two
      factors in the compound's mechanism of action: interferon and a microtubule
      nucleation activator, phosphodiesterase 4D-interacting protein. In particular,
      phosphodiesterase 4D-interacting protein was suggested to be important in
      regulating the trafficking or fusion of prion protein-containing vesicles or
      structures in cells. The findings of the study are expected to be useful not only
      for the elucidation of cellular regulatory mechanisms of prion protein but also
      for the implication of new targets for therapeutic development.

PMID- 24453368
TI  - Evidence of in utero transmission of classical scrapie in sheep.
AB  - Classical scrapie is one of the transmissible spongiform encephalopathies (TSEs),
      a group of fatal infectious diseases that affect the central nervous system
      (CNS). Classical scrapie can transmit laterally from ewe to lamb perinatally or
      between adult animals. Here we report detection of infectivity in tissues of an
      unborn fetus, providing evidence that in utero transmission of classical scrapie
      is also possible. 

PMID- 24453370
TI  - Relocation of the NIb gene in the tobacco etch potyvirus genome.
AB  - Potyviruses express most of their proteins from a long open reading frame that is
      translated into a large polyprotein processed by three viral proteases. To
      understand the constraints on potyvirus genome organization, we relocated the
      viral RNA-dependent RNA polymerase (NIb) cistron to all possible intercistronic
      positions of the Tobacco etch virus (TEV) polyprotein. Only viruses with NIb at
      the amino terminus of the polyprotein or in between P1 and HC-Pro were viable in
      tobacco plants. 

PMID- 24453369
TI  - Fusion activation through attachment protein stalk domains indicates a conserved
      core mechanism of paramyxovirus entry into cells.
AB  - Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA
      viruses causing important diseases in humans and animals. Two viral integral
      membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a
      concerted process of host receptor recognition, followed by the fusion of viral
      and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm.
      However, the sequence of events that closely links the timing of receptor
      recognition by HN, H, or G and the "triggering" interaction of the attachment
      protein with F is unclear. F activation results in F undergoing a series of
      irreversible conformational rearrangements to bring about membrane merger and
      virus entry. By extensive study of properties of multiple paramyxovirus HN
      proteins, we show that key features of F activation, including the F-activating
      regions of HN proteins, flexibility within this F-activating region, and changes
      in globular head-stalk interactions are highly conserved. These results, together
      with functionally active "headless" mumps and Newcastle disease virus HN
      proteins, provide insights into the F-triggering process. Based on these data and
      very recently published data for morbillivirus H and henipavirus G proteins, we
      extend our recently proposed "stalk exposure model" to other paramyxoviruses and
      propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core
      mechanisms of paramyxovirus-mediated membrane fusion. IMPORTANCE: Paramyxoviruses
      are a large family of membrane-enveloped negative-stranded RNA viruses causing
      important diseases in humans and animals. Two viral integral membrane
      glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted
      process of host receptor recognition, followed by the fusion of viral and
      cellular membranes. We describe here the molecular mechanism by which HN
      activates the F protein such that virus-cell fusion is controlled and occurs at
      the right time and the right place. We extend our recently proposed "stalk
      exposure model" first proposed for parainfluenza virus 5 to other paramyxoviruses
      and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved
      core mechanisms of paramyxovirus-mediated membrane fusion.

PMID- 24453371
TI  - Deciphering the role of the Gag-Pol ribosomal frameshift signal in HIV-1 RNA
      genome packaging.
AB  - A key step of retroviral replication is packaging of the viral RNA genome during
      virus assembly. Specific packaging is mediated by interactions between the viral
      protein Gag and elements in the viral RNA genome. In HIV-1, similar to most
      retroviruses, the packaging signal is located within the 5' untranslated region
      and extends into the gag-coding region. A recent study reported that a region
      including the Gag-Pol ribosomal frameshift signal plays an important role in HIV
      1 RNA packaging; deletions or mutations that affect the RNA structure of this
      signal lead to drastic decreases (10- to 50-fold) in viral RNA packaging and
      virus titer. We examined here the role of the ribosomal frameshift signal in HIV
      1 RNA packaging by studying the RNA packaging and virus titer in the context of
      proviruses. Three mutants with altered ribosomal frameshift signal, either
      through direct deletion of the signal, mutation of the 6U slippery sequence, or
      alterations of the secondary structure were examined. We found that RNAs from all
      three mutants were packaged efficiently, and they generate titers similar to that
      of a virus containing the wild-type ribosomal frameshift signal. We conclude that
      although the ribosomal frameshift signal plays an important role in regulating
      the replication cycle, this RNA element is not directly involved in regulating
      RNA encapsidation. IMPORTANCE: To generate infectious viruses, HIV-1 must package
      viral RNA genome during virus assembly. The specific HIV-1 genome packaging is
      mediated by interactions between the structural protein Gag and elements near the
      5' end of the viral RNA known as packaging signal. In this study, we examined
      whether the Gag-Pol ribosomal frameshift signal is important for HIV-1 RNA
      packaging as recently reported. Our results demonstrated that when Gag/Gag-Pol is
      supplied in trans, none of the tested ribosomal frameshift signal mutants has
      defects in RNA packaging or virus titer. These studies provide important
      information on how HIV-1 regulates its genome packaging and generate infectious
      viruses necessary for transmission to new hosts.

PMID- 24453372
TI  - The herpes simplex virus 1 UL51 gene product has cell type-specific functions in
      cell-to-cell spread.
AB  - The herpes simplex virus 1 (HSV-1) UL51 gene encodes a 244-amino-acid (aa)
      palmitoylated protein that is conserved in all herpesviruses. The
      alphaherpesvirus UL51 (pUL51) protein has been reported to function in nuclear
      egress and cytoplasmic envelopment. No complete deletion has been generated
      because of the overlap of the UL51 coding sequence 5' end with the UL52 promoter
      sequences, but partial deletions generated in HSV and pseudorabies virus (PrV)
      suggest an additional function in epithelial cell-to-cell spread. Here we show
      partial uncoupling of the replication, release, and cell-to-cell spread functions
      of HSV-1 pUL51 in two ways. Viruses in which aa 73 to 244 were deleted from pUL51
      or in which a conserved YXXPhi motif near the N terminus was altered showed cell
      specific defects in spread that cannot be accounted for by defects in replication
      and virus release. Also, a cell line that expresses C-terminally enhanced green
      fluorescent protein (EGFP)-tagged pUL51 supported normal virus replication and
      release into the medium but the formation of only small plaques. This cell line
      also failed to support normal localization of gE to cell junctions. gE and pUL51
      partially colocalized in infected cells, and these two proteins could be
      coimmunoprecipitated from infected cells, suggesting that they can form a complex
      during infection. The cell-to-cell spread defect associated with the pUL51
      mutation was more severe than that associated with gE-null virus, suggesting that
      pUL51 has gE-independent functions in epithelial cell spread. IMPORTANCE:
      Herpesviruses establish and reactivate from lifelong latency in their hosts. When
      they reactivate, they are able to spread within their hosts despite the presence
      of a potent immune response that includes neutralizing antibody. This ability is
      derived in part from a specialized mechanism for virus spread between cells. Cell
      to-cell spread is a conserved property of herpesviruses that likely relies on
      conserved viral genes. An understanding of their function may aid in the design
      of vaccines and therapeutics. Here we show that one of the conserved viral genes,
      UL51, has an important role in cell-to-cell spread in addition to its previously
      demonstrated role in virus assembly. We find that its function depends on the
      type of cell that is infected, and we show that it interacts with and modulates
      the function of another viral spread factor, gE.

PMID- 24453373
TI  - Human cytomegalovirus infection of human embryonic stem cell-derived primitive
      neural stem cells is restricted at several steps but leads to the persistence of
      viral DNA.
AB  - Congenital human cytomegalovirus (HCMV) infection is a major cause of central
      nervous system structural anomalies and sensory impairments. It is likely that
      the stage of fetal development, as well as the state of differentiation of
      susceptible cells at the time of infection, affects the severity of the disease.
      We used human embryonic stem (ES) cell-derived primitive prerosette neural stem
      cells (pNSCs) and neural progenitor cells (NPCs) maintained in chemically defined
      conditions to study HCMV replication in cells at the early stages of neural
      development. In contrast to what was observed previously using fetus-derived
      NPCs, infection of ES cell-derived pNSCs with HCMV was nonprogressive. At a low
      multiplicity of infection, we observed only a small percentage of cells
      expressing immediate-early genes (IE) and early genes. IE expression was found to
      be restricted to cells negative for the anterior marker FORSE-1, and treatment of
      pNSCs with retinoic acid restored IE expression. Differentiation of pNSCs into
      NPCs restored IE expression but not the transactivation of early genes. Virions
      produced in NPCs and pNSCs were exclusively cell associated and were mostly non
      neural tropic. Finally, we found that viral genomes could persist in pNSC
      cultures for up to a month after infection despite the absence of detectable IE
      expression by immunofluorescence, and infectious virus could be produced upon
      differentiation of pNSCs to neurons. In conclusion, our results highlight the
      complex array of hurdles that HCMV must overcome in order to infect primitive
      neural stem cells and suggest that these cells might act as a reservoir for the
      virus. IMPORTANCE: Human cytomegalovirus (HCMV) is a betaherpesvirus that is
      highly prevalent in the population. HCMV infection is usually asymptomatic but
      can lead to severe consequences in immunosuppressed individuals. HCMV is also the
      most important infectious cause of congenital developmental birth defects.
      Manifestations of fetal HCMV disease range from deafness and learning
      disabilities to more severe symptoms such as microcephaly. In this study, we have
      used embryonic stem cells to generate primitive neural stem cells and have used
      these to model HCMV infection of the fetal central nervous system (CNS) in vitro.
      Our results reveal that these cells, which are similar to those present in the
      developing neural tube, do not support viral replication but instead likely
      constitute a viral reservoir. Future work will define the effect of viral
      persistence on cellular functions as well as the exogenous signals leading to the
      reactivation of viral replication in the CNS.

PMID- 24453374
TI  - Novel gammaherpesviruses in North American domestic cats, bobcats, and pumas:
      identification, prevalence, and risk factors.
AB  - Gammaherpesviruses (GHVs) are a diverse and rapidly expanding group of viruses
      associated with a variety of disease conditions in humans and animals. To
      identify felid GHVs, we screened domestic cat (Felis catus), bobcat (Lynx rufus),
      and puma (Puma concolor) blood cell DNA samples from California, Colorado, and
      Florida using a degenerate pan-GHV PCR. Additional pan-GHV and long-distance PCRs
      were used to sequence a contiguous 3.4-kb region of each putative virus species,
      including partial glycoprotein B and DNA polymerase genes. We identified three
      novel GHVs, each present predominantly in one felid species: Felis catus GHV 1
      (FcaGHV1) in domestic cats, Lynx rufus GHV 1 (LruGHV1) in bobcats, and Puma
      concolor GHV 1 (PcoGHV1) in pumas. To estimate infection prevalence, we developed
      real-time quantitative PCR assays for each virus and screened additional DNA
      samples from all three species (n = 282). FcaGHV1 was detected in 16% of domestic
      cats across all study sites. LruGHV1 was detected in 47% of bobcats and 13% of
      pumas across all study sites, suggesting relatively common interspecific
      transmission. PcoGHV1 was detected in 6% of pumas, all from a specific region of
      Southern California. The risk of infection for each host varied with geographic
      location. Age was a positive risk factor for bobcat LruGHV1 infection, and age
      and being male were risk factors for domestic cat FcaGHV1 infection. Further
      characterization of these viruses may have significant health implications for
      domestic cats and may aid studies of free-ranging felid ecology. IMPORTANCE:
      Gammaherpesviruses (GHVs) establish lifelong infection in many animal species and
      can cause cancer and other diseases in humans and animals. In this study, we
      identified the DNA sequences of three GHVs present in the blood of domestic cats
      (Felis catus), bobcats (Lynx rufus), and pumas (Puma concolor; also known as
      mountain lions, cougars, and panthers). We found that these viruses were closely
      related to, but distinct from, other known GHVs of animals and represent the
      first GHVs identified to be native to these feline species. We developed
      techniques to rapidly and specifically detect the DNA of these viruses in feline
      blood and found that the domestic cat and bobcat viruses were widespread across
      the United States. In contrast, puma virus was found only in a specific region of
      Southern California. Surprisingly, the bobcat virus was also detected in some
      pumas, suggesting relatively common virus transmission between these species.
      Adult domestic cats and bobcats were at greater risk for infection than
      juveniles. Male domestic cats were at greater risk for infection than females.
      This study identifies three new viruses that are widespread in three feline
      species, indicates risk factors for infection that may relate to the route of
      infection, and demonstrates cross-species transmission between bobcats and pumas.
      These newly identified viruses may have important effects on feline health and
      ecology.

PMID- 24453378
TI  - AACP Council of Sections Report, June 2013.

PMID- 24453375
TI  - Divergent H7 immunogens offer protection from H7N9 virus challenge.
AB  - The emergence of avian H7N9 viruses in humans in China has renewed concerns about
      influenza pandemics emerging from Asia. Vaccines are still the best
      countermeasure against emerging influenza virus infections, but the process from
      the identification of vaccine seed strains to the distribution of the final
      product can take several months. In the case of the 2009 H1N1 pandemic, a vaccine
      was not available before the first pandemic wave hit and therefore came too late
      to reduce influenza morbidity. H7 vaccines based on divergent isolates of the
      Eurasian and North American lineages have been tested in clinical trials, and
      seed strains and reagents are already available and can potentially be used
      initially to curtail influenza-induced disease until a more appropriately matched
      H7N9 vaccine is ready. In a challenge experiment in the mouse model, we assessed
      the efficacy of both inactivated virus and recombinant hemagglutinin vaccines
      made from seed strains that are divergent from H7N9 from each of the two major H7
      lineages. Furthermore, we analyzed the cross-reactive responses of sera from
      human subjects vaccinated with heterologous North American and Eurasian lineage
      H7 vaccines to H7N9. Vaccinations with inactivated virus and recombinant
      hemagglutinin protein preparations from both lineages raised hemagglutination
      inhibiting antibodies against H7N9 viruses and protected mice from stringent
      viral challenges. Similar cross-reactivity was observed in sera of human subjects
      from a clinical trial with a divergent H7 vaccine. Existing H7 vaccine candidates
      based on divergent strains could be used as a first line of defense against an
      H7N9 pandemic. In addition, this also suggests that H7N9 vaccines that are
      currently under development might be stockpiled and used for divergent avian H7
      strains that emerge in the future. IMPORTANCE: Sporadic human infections with
      H7N9 viruses started being reported in China in the early spring of 2013. Despite
      a significant drop in the number of infections during the summer months of 2013,
      an increased number of cases has already been reported for the 2013-2014 winter
      season. The high case fatality rate, the ability to bind to receptors in the
      human upper respiratory tract in combination with several family clusters, and
      the emergence of neuraminidase inhibitor-resistant variants that show no loss of
      pathogenicity and the ability to transmit in animal models have raised concerns
      about a potential pandemic and have spurred efforts to produce vaccine
      candidates. Here we show that antigen preparations from divergent H7 strains are
      able to induce protective immunity against H7N9 infection.

PMID- 24453379
TI  - Bayesian influence analysis: a geometric approach.
AB  - In this paper we develop a general framework of Bayesian influence analysis for
      assessing various perturbation schemes to the data, the prior and the sampling
      distribution for a class of statistical models. We introduce a perturbation model
      to characterize these various perturbation schemes. We develop a geometric
      framework, called the Bayesian perturbation manifold, and use its associated
      geometric quantities including the metric tensor and geodesic to characterize the
      intrinsic structure of the perturbation model. We develop intrinsic influence
      measures and local influence measures based on the Bayesian perturbation manifold
      to quantify the effect of various perturbations to statistical models.
      Theoretical and numerical examples are examined to highlight the broad spectrum
      of applications of this local influence method in a formal Bayesian analysis.

PMID- 24453380
TI  - Inferences on Small Area Proportions.
AB  - Design-based methods are generally inefficient for making inferences about small
      area proportions for rare events. In this paper, we discuss an alternative
      hierarchical model and the associated hierarchical Bayes methodology. Sufficient
      conditions for propriety of the posterior distributions of relevant parameters
      are presented.

PMID- 24453381
TI  - Nanodomain induced anomalous magnetic and electronic transport properties of
      LaBaCo2O5.5+delta highly epitaxial thin films.
AB  - A giant magnetoresistance effect (~46% at 20 K under 7 T) and anomalous magnetic
      properties were found in a highly epitaxial double perovskite LaBaCo2O5.5+delta
      (LBCO) thin film on (001) MgO. Aberration-corrected Electron Microscopy and
      related analytical techniques were employed to understand the nature of these
      unusual physical properties. The as-grown film is epitaxial with the c-axis of
      the LBCO structure lying in the film plane and with an interface relationship
      given by (100)LBCO || (001)MgO and [001]LBCO || [100]MgO or [010]MgO. Orderly
      oxygen vacancies were observed by line profile electron energy loss spectroscopy
      and by atomic resolution imaging. Especially, oxygen vacancy and nanodomain
      structures were found to have a crucial effect on the electronic transport and
      magnetic properties.

PMID- 24453382
TI  - Synthesis and evaluation of antiproliferative activity of substituted N-(9-oxo-9H
      xanthen-4-yl)benzenesulfonamides.
AB  - Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were
      prepared as potential antiproliferative agents. The in vitro antiproliferative
      activity of the synthesized compounds was investigated against a panel of tumor
      cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and
      neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well
      known anticancer drug, was used as a positive standard drug. Among synthesized
      compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the
      highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells.
      Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative
      activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast
      adenocarcinoma (MDA-MB-468) cells. Structure-activity relationship studies
      revealed that xanthone benzenesulfonamide hybrid compounds can be used for
      development of new lead anticancer agents.

PMID- 24453383
TI  - Cross-linguistic differences in prosodic cues to syntactic disambiguation in
      German and English.
AB  - This study examined whether late-learning English-German L2 learners and late
      learning German-English L2 learners use prosodic cues to disambiguate temporarily
      ambiguous L1 and L2 sentences during speech production. Experiments 1a and 1b
      showed that English-German L2 learners and German-English L2 learners used a
      pitch rise and pitch accent to disambiguate prepositional phrase-attachment
      sentences in German. However, the same participants, as well as monolingual
      English speakers, only used pitch accent to disambiguate similar English
      sentences. Taken together, these results indicate the L2 learners used prosody to
      disambiguate sentences in both of their languages and did not fully transfer cues
      to disambiguation from their L1 to their L2. The results have implications for
      the acquisition of L2 prosody and the interaction between prosody and meaning in
      L2 production.

PMID- 24453384
TI  - Rural dementia carers: formal and informal sources of support.
AB  - Primary carers provide much of the day-to-day care for community-dwelling people
      living with dementia (PWD). Maintaining that contribution will require a more in
      depth understanding of the primary carer role and the support needs that flow
      from that role. This study explored patterns of formal and informal support
      utilisation by people caring for a PWD in a rural-regional context. In-depth semi
      structured interviews were conducted with 18 rural primary carers of a PWD and
      thematically analysed. Participant primary carers' almost total commitment to,
      and absorption in their role and their assumption of ultimate responsibility for
      the PWD's wellbeing meant that external social context, such as rurality, became
      less relevant. Carer networks effectively contracted to those key individuals who
      were central to supporting them in their caring task. External sources of support
      were tightly managed with strong boundaries around the provision of direct care
      to the PWD largely excluding all but professional providers. Primary carers are
      generally categorised along with other family and friends as informal care.
      However, in assuming primary responsible for the care and wellbeing for the PWD
      they effectively become the key care provider, suggesting that it would be
      productive in both research and practice to treat primary carers as key members
      of a care partnership alongside professional carers, rather than as adjuncts to
      formal care and/or another client.

PMID- 24453385
TI  - Trust-Based Relational Intervention (TBRI): A Systemic Approach to Complex
      Developmental Trauma.
AB  - Children and youth who have experienced foster care or orphanage-rearing have
      often experienced complex developmental trauma, demonstrating an interactive set
      of psychological and behavioral issues. Trust-Based Relational Intervention
      (TBRI) is a therapeutic model that trains caregivers to provide effective support
      and treatment for at-risk children. TBRI has been applied in orphanages, courts,
      residential treatment facilities, group homes, foster and adoptive homes,
      churches, and schools. It has been used effectively with children and youth of
      all ages and all risk levels. This article provides the research base for TBRI
      and examples of how it is applied.

PMID- 24453386
TI  - Breast Cancer-Screening Behavior among Rural California American Indian Women.

PMID- 24453387
TI  - Modeling Disease Progression with Longitudinal Markers.
AB  - In this paper we propose a Bayesian natural history model for disease progression
      based on the joint modeling of longitudinal biomarker levels, age at clinical
      detection of disease and disease status at diagnosis. We establish a link between
      the longitudinal responses and the natural history of the disease by using an
      underlying latent disease process which describes the onset of the disease and
      models the transition to an advanced stage of the disease as dependent on the
      biomarker levels. We apply our model to the data from the Baltimore Longitudinal
      Study of Aging on prostate specific antigen (PSA) to investigate the natural
      history of prostate cancer.

PMID- 24453388
TI  - Association between Tumor Necrosis Factor- alpha-308 G/A Polymorphism and
      Multiple Sclerosis: A Systematic Review and Meta-Analysis.
AB  - Multiple sclerosis (MS) is a complex polygenic disease in which gene-environment
      interactions are important. A number of studies have investigated the association
      between tumor necrosis factor-alpha (TNF-alpha) -308 G/A polymorphism
      (substitution G->A, designated as TNF1 and TNF2) and MS susceptibility in
      different populations, but the results of individual studies have been
      inconsistent. Therefore, performing a systematic review and meta-analysis of the
      published studies is desirable. We sought to quantitatively summarize the
      association between TNF-alpha-308 G/A polymorphism and MS. The Medline and Scopus
      databases were searched to identify potentially relevant case-control studies
      published in English journals up to January 2010. A meta-analysis of these
      studies was performed. Summary odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated under fixed and random effects models. Twenty-one eligible
      studies, comprising 2880 patients with MS and 3579 controls, were included in the
      meta-analysis. The overall pooled ORs (95%CI) for TNF2 versus TNF1 and TNF2
      carriers (2/2+2/1) versus non-carriers (1/1) were 1.02 (0.86-1.21) and 0.99 (0.8
      1.24), respectively. In the European populations, the pooled ORs (95%CI) for TNF
      2/1 versus 1/1 were 0.85 (0.73-0.98), which was statistically significant.
      However, the other results did not support this finding. The pooled ORs (95%CI)
      for TNF 2/1 versus 1/1 and TNF 2/2 versus 2/1 were not statistically significant
      in the overall population. In addition, the pooled ORs for TNF2/2 versus
      TNF2/1+1/1 and TNF2/2 versus TNF1/1 were not statistically significant. Our meta
      analysis does not support the role of TNF-alpha -308 G/A polymorphism in
      developing MS. 

PMID- 24453389
TI  - Intraocular Pressure Measurements by Three Different Tonometers in Children with
      Aphakic Glaucoma and a Thick Cornea.
AB  - BACKGROUND: To evaluate the agreement in intraocular pressure (IOP) measurements
      by Ocular Response Analyzer (ORA) and Tono-Pen XL (TXL) with the Goldmann
      Applanation Tonometer (GAT) and to examine corneal biomechanical properties in
      aphakic glaucoma patients with a central corneal thickness (CCT) >600 u. METHODS:
      Thirty-six eyes of aphakic glaucoma patients (group 1) and 40 eyes of normal
      children (group 2) were studied. The mean ORA and TXL IOP values were compared
      with the GAT-IOP values. Regression analyses were used to evaluate the
      associations between IOP and CCT, corneal hysteresis (CH), and corneal resistance
      factor (CRF). Bland-Altman plots were used to evaluate the agreement between the
      tonometers. RESULTS: The mean+/-standard deviations of the age and male/female
      ratio were 16.58+/-5.44 and 15.75+/-5.04 years and 14/22 and 18/22 in group 1 and
      group 2, respectively. CCT in group 1 was 651.1+/-42 and in group 2 was 567.3+/
      32.4. In group 1, the mean TXL (22.4, P=0.004), IOPcc (corneal compensated)
      (27.8, P=0.005), and IOPg (Goldmann correlated) values (28.1, P<0.0001) were
      greater than GAT-IOP (20.6). In group 2, only IOPg value (16.4) was higher than
      GAT-IOP (14.8, P=0.04). IOP reading of all the tonometers were positively and
      negatively associated with CRF and CH in the multiple regression analysis,
      respectively. CONCLUSION: The TXL had a greater agreement with the GAT, and the
      ORA overestimated IOP in aphakic glaucoma patients. The ORA and TXL seemed to be
      affected by CH and CRF.

PMID- 24453390
TI  - Effect of follicular fluid and platelet-activating factor on lactate
      dehydrogenase C expression in human asthenozoospermic samples.
AB  - BACKGROUND: Application of follicular fluid (FF) and platelet-activating factor
      (PAF) in artificial insemination improves sperm motility. Lactate dehydrogenase C
      (LDH-C) is a key enzyme for sperm motility. In this study, the effects of FF and
      PAF on the sperm motility index and LDH-C expression were investigated. Moreover,
      LDH-C expression was compared between asthenozoospermic and normozoospermic
      samples. METHODS: The expression of LDH-C was examined by quantitative real-time
      polymerase chain reaction (q-RT PCR) and western blotting after it was treated
      with optimized concentrations of FF and PAF in twenty asthenozoospermic samples.
      Also, LDH-C expression was evaluated in five normozoospermic samples. RESULTS:
      Samples with 75% FF and 100 nM of PAF had an increase in their percentages of
      progressive and slowly motile sperms and a decrease in their percentages of non
      progressive and non-motile sperms. Moreover, LDH-C mRNA transcripts were not
      changed following PAF and FF treatment, and LDH-C protein was detected in highly
      progressive motile specimens treated with FF in the asthenozoospermic samples.
      Furthermore, LDH-C expression was more detectable in the normal sperms.
      CONCLUSION: Our results indicated that PAF had more beneficial effects than FF on
      sperm motility in the asthenozoospermic samples (P=0.0001), although the LDH-C
      expressions of the sperms were not changed significantly in both groups. We found
      no association between LDH-C expression and sperm motility after FF and PAF
      actions. This finding, however, requires further investigation. The fact that LDH
      C protein was detected in the normozoospermic, but not asthenozoospermic, samples
      could be cited as a reason for the infertility in these patients.

PMID- 24453391
TI  - Skin Prick Test Reactivity to Common Aero and Food Allergens among Children with
      Allergy.
AB  - BACKGROUND: The prevalence of allergic diseases has risen in the last decades.
      The objective of this study was to determine the common allergens in children via
      the skin prick test. METHODS: This cross-sectional study recruited 313 allergic
      children (4 months to 18 years old) referred to the Asthma and Allergy Clinic of
      Children's Medical Center in Tehran. A questionnaire containing demographic data
      and patient history was completed. The Skin Prick Test (SPT) was selected
      according to the patients' history of food and/or aeroallergen sensitivity.
      RESULTS: Patients (62.4% male, 37.6% female) with symptoms of asthma (n=141,
      57.1%), allergic rhinitis (n=50, 20.4%), atopic dermatitis (n=29, 11.7%), and
      urticaria (n=20, 8.1%) were studied. Positive skin prick test to at least one
      allergen was 58.1%. The most prevalent allergens were tree mix (26%), Alternaria
      alternata (26%), weed mix (23.6%), Dermatophagoides farinae (22.9%),
      Dermatophagoides pteronyssinus (22.9%), milk (21.7%), eggs (20%), and wheat flour
      (18.3%). Also, common allergens in the patients with different symptoms of
      allergic disorders were as follows: asthma (tree mix, weed mix, and
      Dermatophagoides farinae); allergic rhinitis (Dermatophagoides farinae, tree mix,
      and Dermatophagoides pteronyssinus); and atopic dermatitis (Alternaria alternata,
      Dermatophagoides pteronyssinus, and cockroaches). CONCLUSION: Identifying
      allergens in each area is necessary and has an important role in the diagnosis
      and management of allergic disorders and possibility of performing immunotherapy.
      In this study, the most common aeroallergens were tree mix, Alternaria alternata,
      and weed mix and also the most common food allergens were milk, eggs, and wheat.
      Considering these data, appropriate preventive strategies can decrease the cost
      and morbidity of therapeutic actions.

PMID- 24453392
TI  - In Vitro Antibacterial Activity of Several Plant Extracts and Oils against Some
      Gram-Negative Bacteria.
AB  - BACKGROUND: Medicinal plants are considered new resources for producing agents
      that could act as alternatives to antibiotics in the treatment of antibiotic
      resistant bacteria. The aim of this study was to evaluate the antibacterial
      activity of 28 plant extracts and oils against four Gram-negative bacterial
      species. METHODS: Experimental, in vitro, evaluation of the activities of 28
      plant extracts and oils as well as some antibiotics against E. coli O157:H7,
      Yersinia enterocolitica O9, Proteus spp., and Klebsiella pneumoniae was
      performed. The activity against 15 isolates of each bacterium was determined by
      disc diffusion method at a concentration of 5%. Microdilution susceptibility
      assay was used in order to determine the minimal inhibitory concentrations (MICs)
      of the plant extracts, oils, and antibiotics. RESULTS: Among the evaluated herbs,
      only Origanum syriacum L., Thymus syriacus Boiss., Syzygium aromaticum L.,
      Juniperus foetidissima Wild, Allium sativum L., Myristica fragrans Houtt, and
      Cinnamomum zeylanicum L. essential oils and Laurus nobilis L. plant extract
      showed anti-bacterial activity. The MIC50 values of these products against the
      Gram-negative organisms varied from 1.5 (Proteus spp. and K. pneumoniae( and 6.25
      ul/ml (Yersinia enterocolitica O9 ) to 12.5 ul/ml (E. coli O:157). CONCLUSION:
      Among the studied essential oils, O. syriacum L., T. syriacus Boiss., C.
      zeylanicum L., and S. aromaticum L. essential oils were the most effective.
      Moreover, Cephalosporin and Ciprofloxacin were the most effective antibiotics
      against almost all the studied bacteria. Therefore, O. syriacum L., T. syriacus
      Boiss., C. zeylanicum L., and S. aromaticum L. could act as bactericidal agents
      against Gram-negative bacteria.

PMID- 24453393
TI  - Modulatory effect of gonadotropins on rats' ovaries after nandrolone decanoate
      administration: a stereological study.
AB  - BACKGROUND: Nandrolone decanoate (ND) is an anabolic androgenic steroid (AAS)
      which influences the ovarian structure and function. We assessed the effects of
      ND on the ovarian volume, number of primordial follicles, and level of hormones
      and also evaluated the modulatory effects of gonadotropins on the
      histopathological changes imposed by the administration of ND. METHODS: Six
      groups of Sprague-Dawley adult female rats (n=30) were used. The experimental
      rats were injected intraperitoneally with 3 and 10 mg/kg ND with or without human
      menopausal gonadotropin (hMG), 10 IU weekly for one month. The vehicle and
      control rats were administered olive oil and saline, respectively, for the same
      period of time. The ovarian volume and number of primordial follicles were
      estimated by stereological methods. RESULTS: The results showed a decrease in the
      ovarian volume, number of primordial follicles, and level of gonadotropins in the
      ND-treated animals compared with the vehicle groups. In the rats treated with 3
      mg/kg of ND with hMG, an increase in the ovarian volume and number of primordial
      follicles was shown as compared to the rats treated with the same dose of ND
      without hMG. CONCLUSION: ND exerted detrimental effects on the dimensions of the
      ovary, number of follicles, and level of sex hormones. However, hMG, prevented
      the harmful effects of ND (at least in a low dose) on the ovarian follicles.

PMID- 24453394
TI  - Effects of Short-term Renovascular Hypertension and Type 2 Diabetes on Cardiac
      Functions in Rats.
AB  - BACKGROUND: The cardiac effects simultaneously occurring during experimental
      hypertension and diabetes have rarely been investigated. This study aimed at
      examining the effects of short-term renovascular hypertension and type 2 diabetes
      on cardiac functions. METHODS: Five groups (7 each) of male Sprague-Dawley rats,
      including a control group, a diabetes (induced by Streptozocin and Nicotinamide)
      group, a renovascular hypertensive (induced by placing Plexiglas clips on the
      left renal arteries) group, a sham group, and a simultaneously hypertensive
      diabetic group, were used. The animals' hearts were used for isolated heart
      studies, and the indices of cardiac functions and coronary effluent creatine
      kinase MB were measured. The results were analyzed using One-way Analysis of
      Variance, followed by the Duncan Multiple Range test. RESULTS: The diabetic group
      had a significantly lower rate of rise (-29.5%) and decrease (-36.18%) in
      ventricular pressure, left ventricular developed pressure (-28.8%), and rate
      pressure product (-35%), and significantly higher creatine kinase MB (+166%) and
      infarct size (+36.2%) than those of the control group. The hypertensive group had
      a significantly higher rate of rise (+12.17%) and decrease (+16.2%) in
      ventricular pressure, left ventricular developed pressure (+16%), and rate
      pressure product (+24%), and significantly lower creatine kinase MB (-30%) and
      infarct size (-27%) than those of the sham group. Simultaneously, the diabetic
      and hypertensive rats had a significantly higher rate of rise (+32%) and decrease
      (+30.2%) in ventricular pressure, left ventricular developed pressure (+17.2%),
      and rate pressure product (+22.2%), and significantly lower creatine kinase MB (
      24%) and infarct size (-16.2%) than those of the diabetic group. CONCLUSION: The
      findings indicated that the simultaneity of hypertension with type 2 diabetes
      attenuated diabetes-induced cardiac impairment.

PMID- 24453395
TI  - Hypothyroidism in beta-Thalassemia Intermedia Patients with and without
      Hydroxyurea.
AB  - Hydroxyurea (HU) has been successfully used in patients with beta-thalassemia
      intermedia (beta-TI). We aimed to evaluate the effect of the long-term use of HU
      on thyroid function in patients with beta-TI. Seventy-five patients with beta-TI
      aged>=11 years and taking HU were randomly selected during 2010 in southern Iran.
      Thirty-one patients with beta-TI without HU were considered as a control group.
      Serum levels of thyroid stimulating hormone (TSH) and T4 were measured. The mean
      age of the participants was 22.7+/-5.1 years (age range=12-41 years). Serum
      ferritin level had no significant correlation with HU consumption (P>0.05).
      Overall, we detected 10 (9.4%) patients with hypothyroidism. We found that the
      use of HU at a dose of 8-15 mg/kg/day has no significant association with thyroid
      function in beta-TI patients. However, due to the small sample size in our study,
      documentation of this finding needs further studies with higher numbers of
      patients. 

PMID- 24453396
TI  - Urinary melatonin levels and skin malignancy.
AB  - Melatonin inhibits tumor genesis in a variety of in vivo and in vitro
      experimental models of neoplasia. In industrialized societies, light at night, by
      suppressing melatonin production, poses a new risk for the development of a
      variety of cancers such as breast cancer. This effect on skin has been previously
      studied only in animals and not in humans. Our goal was to examine the
      relationship between 24-hour 6-sulphatoxymelatonin levels and skin cancer in a
      case-control study of 70 patients with skin cancer and 70 healthy individuals.
      The level of 6-sulfatoxymelatonin was measured in 24-hour urine by the ELISA
      method. In the case group, 55 (78%) patients had basal cell carcinoma and 15
      (22%) had squamous cell carcinoma. The mean level of 24-hour urine 6
      sulfatoxymelatonin was significantly higher in the control group (P<0.001). Also,
      sleep duration had a significant difference between the two groups (P=0.001). It
      seems that a low level of 24-hour urinary 6-sulfatoxymelatonin renders human
      beings prone to skin cancer. This association, however, requires further
      investigation. 

PMID- 24453397
TI  - Intestinal pseudo-obstruction as an unusual gastrointestinal presentation in
      pediatric human immunodeficiency virus infection.
AB  - Intestinal pseudo-obstruction is a condition in which the intestine's ability to
      push food through is reduced. It often leads to the dilation of the various parts
      of the bowel. It can be idiopathic or inherited from a parent, or caused by
      another disease. We report a rare case of human immunodeficiency virus (HIV)
      infection in a 3-year-old boy who referred with acute abdominal pain, and was
      later diagnosed as having intestinal pseudo-obstruction caused by HIV. The
      underlying causes of intestinal pseudo-obstruction should be taken into account.
      HIV induced pseudo-obstruction may be considered in the differential diagnosis of
      pediatric intestinal pseudo-obstruction in order to provide a timely diagnosis
      and optimal care of children with HIV. 

PMID- 24453398
TI  - Peripheral primitive neuroectodermal tumor of the pelvis.
AB  - The primitive neuroectodermal tumor (PNET) belongs to a group of highly malignant
      tumors and is composed of small round cells of a neuroectodermal origin.
      Categorized in the same tumor family as Ewing sarcoma, the PNET is most likely to
      occur in bones and soft tissues. However, a small number of PNET cases arising in
      the pelvis have been reported as well. WE PRESENT THREE CASES OF PELVIC PNET: two
      cases in the ovary and one case in the broad ligament. The PNET often exhibits
      aggressive clinical behavior with worse outcomes than other small round cell
      tumors. The significant prognostic factors of the PNET include site of tumor,
      volume of neoplasm, and presence of metastasis. The treatment protocol is
      multimodal and includes local surgical treatment followed by chemotherapy. We
      herein describe three PNET cases as a rare entity in the pelvis. Pelvic PNETs
      should be included in the differential diagnosis of pelvic masses.

PMID- 24453399
TI  - Stone composition in patients who undergo renal stone surgery: review of 423
      stone analyses in southern iran.

PMID- 24453400
TI  - Magnetic resonance imaging of vermian lipoma.

PMID- 24453402
TI  - Ambivalent Sexism Revisited.

PMID- 24453403
TI  - Discussion of "Estimating Random Effects via Adjustment for Density Maximization"
      by C. Morris and R. Tang.

PMID- 24453404
TI  - Why won't you do what I want? The informative failures of children and models.
AB  - Computational models are powerful tools - too powerful, according to some. We
      argue that the idea that models can "do anything" is wrong, and describe how
      their failures have been informative. We present new work showing surprising
      diversity in the effects of feedback on children's task-switching, such that some
      children perseverate despite this feedback, other children switch as instructed,
      and yet others play an "opposites" game without truly switching to the newly
      instructed task. We present simulations that demonstrate the failure of an
      otherwise-successful neural network model to capture this failure of children.
      Simulating this pattern motivates the inclusion of updating mechanisms that make
      contact with a growing literature on frontostriatal function, despite their
      absence in extant theories of the development of cognitive flexibility. We argue
      from this and other examples that computational models are more constrained than
      is typically acknowledged, and that their resulting failures can be theoretically
      illuminating.

PMID- 24453405
TI  - Interference Suppression vs. Response Inhibition: An Explanation for the Absence
      of a Bilingual Advantage in Preschoolers' Stroop Task Performance.
AB  - The well-documented advantage that bilingual speakers demonstrate across the
      lifespan on measures of controlled attention is not observed in preschoolers'
      performance on Stroop task variations. We examined the role of task demands in
      explaining this discrepancy. Whereas the Color/Word Stroop used with adult
      participants requires interference suppression, the Stroop task typically used
      with preschoolers requires only response inhibition. We developed an age
      appropriate conflict task that measures interference suppression. Fifty-one
      preschool children (26 bilinguals) completed this new Color/Shape task and the
      Day/Night task used in previous research. Bilingual in comparison to monolingual
      children performed better on incongruent trials of the Color/Shape task, but did
      not differ on other measures. The results indicate that the discrepancy between
      preschoolers and older individuals in performance on Stroop task adaptations
      results from characteristics of the task rather than developmental differences.
      Further, the findings provide additional support for the importance of
      interference suppression as a mechanism underlying the bilingual advantage.

PMID- 24453406
TI  - Discriminating Among Probability Weighting Functions Using Adaptive Design
      Optimization.
AB  - Probability weighting functions relate objective probabilities and their
      subjective weights, and play a central role in modeling choices under risk within
      cumulative prospect theory. While several different parametric forms have been
      proposed, their qualitative similarities make it challenging to discriminate
      among them empirically. In this paper, we use both simulation and choice
      experiments to investigate the extent to which different parametric forms of the
      probability weighting function can be discriminated using adaptive design
      optimization, a computer-based methodology that identifies and exploits model
      differences for the purpose of model discrimination. The simulation experiments
      show that the correct (data-generating) form can be conclusively discriminated
      from its competitors. The results of an empirical experiment reveal heterogeneity
      between participants in terms of the functional form, with two models (Prelec-2,
      Linear in Log Odds) emerging as the most common best-fitting models. The findings
      shed light on assumptions underlying these models.

PMID- 24453407
TI  - Relation between dairy food intake and cognitive function: The Maine-Syracuse
      Longitudinal Study.
AB  - Diet modification to alter the course of age-related cognitive decline is
      becoming increasingly important. Few observational findings suggest that dairy
      food intake may be positively related to cognitive function, but research in this
      novel area is limited. The aim of this study was to investigate whether dairy
      food intake is associated with cognitive function, before and after adjustment
      for cardiovascular, lifestyle and dietary factors. To do this, a cross-sectional
      analyses of a subset of the community-based Maine-Syracuse Longitudinal Study
      (MSLS) sample (N = 972) was undertaken. It was determined that participants who
      consumed dairy products at least once per day had significantly higher scores on
      multiple domains of cognitive function compared with those who never or rarely
      consumed dairy foods, adjusting for cardiovascular risk factors, lifestyle and
      dietary factors. Frequent dairy food intake is associated with better cognitive
      performance but underlying causal mechanisms are still to be determined.

PMID- 24453408
TI  - Genes related to mitochondrial functions, protein degradation, and chromatin
      folding are differentially expressed in lymphomonocytes of Rett syndrome
      patients.
AB  - Rett syndrome (RTT) is mainly caused by mutations in the X-linked methyl-CpG
      binding protein (MeCP2) gene. By binding to methylated promoters on CpG islands,
      MeCP2 protein is able to modulate several genes and important cellular pathways.
      Therefore, mutations in MeCP2 can seriously affect the cellular phenotype. Today,
      the pathways that MeCP2 mutations are able to affect in RTT are not clear yet.
      The aim of our study was to investigate the gene expression profiles in
      peripheral blood lymphomonocytes (PBMC) isolated from RTT patients to try to
      evidence new genes and new pathways that are involved in RTT pathophysiology.
      LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of
      Microarrays) analyses on microarray data from 12 RTT patients and 7 control
      subjects identified 482 genes modulated in RTT, of which 430 were upregulated and
      52 were downregulated. Functional clustering of a total of 146 genes in RTT
      identified key biological pathways related to mitochondrial function and
      organization, cellular ubiquitination and proteosome degradation, RNA processing,
      and chromatin folding. Our microarray data reveal an overexpression of genes
      involved in ATP synthesis suggesting altered energy requirement that parallels
      with increased activities of protein degradation. In conclusion, these findings
      suggest that mitochondrial-ATP-proteasome functions are likely to be involved in
      RTT clinical features. 

PMID- 24453409
TI  - Significant association between serum interleukin-6 and Helicobacter pylori
      antibody levels among H. pylori-positive Japanese adults.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine produced by many
      types of cells. Inflammation plays a key role in the pathogenesis of
      atherosclerosis that is an underlying cause of coronary heart disease (CHD).
      Since the 1990s, some studies have shown an association between H. pylori
      infection and CHD, which may be mediated by inflammation. Therefore, this study
      aimed to evaluate the association between serum anti-H. pylori IgG levels and
      serum IL-6 levels in H. pylori-infected adults. METHODS: We enrolled 158 subjects
      who visited a clinic located in an urban area to be tested for H. pylori
      infection, using the (13)C-urea breath test, and who were found to be infected
      and subsequently received eradication. RESULTS: The geometric mean serum IL-6
      level was 1.78 pg/mL for men, 1.57 pg/mL for women, and 1.64 pg/mL overall.
      Logarithms of serum IL-6 levels were positively correlated with logarithms of
      serum H. pylori IgG levels (r = 0.24, P = 0.002). In multiple linear regression
      analysis adjusting for sex and age, the serum IL-6 level was still significantly
      associated with the IgG level in all subjects (beta = 0.18, P = 0.012).
      CONCLUSION: Higher H. pylori IgG levels were significantly associated with higher
      serum IL-6 levels among H. pylori-infected individuals.

PMID- 24453410
TI  - Induction of tumor necrosis factor (TNF) release from subtypes of T cells by
      agonists of proteinase activated receptors.
AB  - Serine proteinases have been recognized as playing an important role in
      inflammation via proteinase activated receptors (PARs). However, little is known
      about the influence of serine proteinases and PARs on TNF secretion from highly
      purified T cells. We challenged T cells from human peripheral blood with serine
      proteinases and agonist peptides of PARs and measured the levels of TNF in
      culture supernatants by ELISA. The results showed that thrombin and trypsin, but
      not tryptase, stimulated approximately up to 2.5-fold increase in TNF release
      from T cells following 16 h incubation. Proteinase inhibitors and PAR-1
      antagonist SCH 79797 almost completely abolished thrombin- and trypsin-induced
      TNF release from T cells. Agonist peptides of PAR-1, but not PAR-2 induced TNF
      release from T cells. Moreover, trypsin- and thrombin-induced upregulated
      expression of TNF was observed in CD4+, IL-4+, or CD25+ T cells, but not in IFN+
      or IL-17+ T cells. The signaling pathways MAPK/ERK and PI3K/Akt are involved in
      the thrombin- and trypsin-induced TNF release from T cells. In conclusion,
      thrombin and trypsin can induce TNF release from IL-4+ and CD25+ T cells through
      activation of PAR-1 and therefore contribute to regulation of immune response and
      inflammation of the body. 

PMID- 24453411
TI  - TNF- alpha and IFN-s-dependent muscle decay is linked to NF-kappaB- and STAT
      1alpha-stimulated Atrogin1 and MuRF1 genes in C2C12 myotubes.
AB  - TNF-alpha was shown to stimulate mitogenicity in C2C12 myoblasts. Selected
      cytokines TNF-alpha, IFNalpha, or IFNgamma reduced the expression of myosin heavy
      chain (MyHC IIa) when given together. Molecular mechanisms of cytokine activities
      were controlled by NF-kappaB and JAK/STAT signaling pathways, as metabolic
      inhibitors, curcumin and AG490, inhibited some of TNF-alpha and IFNalpha/IFNgamma
      effects. Insulin was hardly antagonistic to TNF-alpha - and IFNalpha/IFNgamma
      dependent decrease in MyHC IIa protein expression. Cytokines used individually or
      together also repressed myogenesis of C2C12 cells. Moreover, TNF-alpha - and
      IFNalpha/IFNgamma-dependent effects on C2C12 myotubes were associated with
      increased activity of Atrogin1 and MuRF1 genes, which code ubiquitin ligases.
      MyHC IIa gene activity was unaltered by cytokines. Inhibition of NF-kappaB or
      JAK/STAT with specific metabolic inhibitors decreased activity of Atrogin1 and
      MuRF1 but not MyHC IIa gene. Overall, these results suggest cooperation between
      cytokines in the reduction of MyHC IIa protein expression level via NF
      kappaB/JAK/STAT signaling pathways and activation of Atrogin1 and MuRF1 genes as
      their molecular targets. Insulin cotreatment or pretreatment does not protect
      against muscle decay induced by examined proinflammatory cytokines.

PMID- 24453412
TI  - Endobronchial perfluorocarbon reduces inflammatory activity before and after lung
      transplantation in an animal experimental model.
AB  - BACKGROUND: The aim of this study was to evaluate the use of liquid
      perfluorocarbon (PFC) as an adjuvant substance for lung preservation and assess
      its role in pulmonary protection after transplantation. METHODS: Seventy-two rat
      lungs were flushed with low-potassium dextran (LPD) solution and randomized into
      three main groups: control with LPD alone and experimental with 3 (PFC3) and 7
      mL/kg (PFC7) of endobronchial PFC instilled just after harvest. Each group was
      divided into four subgroups according to preservation time (3, 6, 12, and 24
      hours). Afterwards, we performed lung transplantation using rat lungs preserved
      for 12 hours with LPD alone or with 7 mL/kg of endobronchial PFC. RESULTS: There
      was a significant increase in oxidative stress in the control group at 6 h of
      cold ischemic time compared with the PFC3 and PFC7 groups. The apoptotic activity
      and NF-kappaB expression were significantly higher in the control group compared
      with the PFC groups at 3, 12, and 24 h of cold preservation. After
      transplantation, the NF-kappaB, iNOS, and nitrotyrosine expression as well as
      caspase 3 activity were significantly lower in the PFC groups. CONCLUSION: The
      use of endobronchial PFC as an adjuvant to the current preservation strategy
      improved graft viability.

PMID- 24453413
TI  - IRF5 is a specific marker of inflammatory macrophages in vivo.
AB  - Macrophages are an integral part of the innate immune system and key players in
      pathogen clearance and tissue remodelling. Both functions are accomplished by a
      pivotal network of different macrophage subtypes, including proinflammatory M1
      and anti-inflammatory M2 macrophages. Previously, our laboratory identified the
      transcription factor interferon regulatory factor 5 (IRF5) as the master
      regulator of the M1 macrophage polarisation. IRF5 was found to be highly
      expressed in human M1 compared to M2 macrophages. Furthermore, IRF5 dictates the
      expression of proinflammatory genes such as IL12b and IL23a whilst repressing
      anti-inflammatory genes like IL10. Here we show that murine bone marrow derived
      macrophages differentiated in vitro with GM-CSF are also characterised by high
      levels of IRF5 mRNA and protein and express proinflammatory cytokines upon LPS
      stimulation. These macrophages display characteristic expression of M1-marker MHC
      II but lack the M2-marker CD206. Significantly, we develop intracellular staining
      of IRF5- expressing macrophages and utilise it to recapitulate the in vitro
      results in an in vivo model of antigen-induced arthritis, emphasising their
      physiological relevance. Thus, we establish the species-invariant role of IRF5 in
      controlling the inflammatory macrophage phenotype both in vitro and in in vivo. 

PMID- 24453414
TI  - The role of TL1A and DR3 in autoimmune and inflammatory diseases.
AB  - TNF-like ligand 1A (TL1A), which binds its cognate receptor DR3 and the decoy
      receptor DcR3, is an identified member of the TNF superfamily. TL1A exerts
      pleiotropic effects on cell proliferation, activation, and differentiation of
      immune cells, including helper T cells and regulatory T cells. TL1A and its two
      receptors expression is increased in both serum and inflamed tissues in
      autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid
      arthritis (RA), and ankylosing spondylitis (AS). Polymorphisms of the TNFSF15
      gene that encodes TL1A are associated with the pathogenesis of irritable bowel
      syndrome, leprosy, and autoimmune diseases, including IBD, AS, and primary
      biliary cirrhosis (PBC). In mice, blocking of TL1A-DR3 interaction by either
      antagonistic antibodies or deletion of the DR3 gene attenuates the severity of
      multiple autoimmune diseases, whereas sustained TL1A expression on T cells or
      dendritic cells induces IL-13-dependent small intestinal inflammation. This
      suggests that modulation of TL1A-DR3 interaction may be a potential therapeutic
      target in several autoimmune diseases, including IBD, RA, AS, and PBC. 

PMID- 24453415
TI  - 4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and
      periodontal inflammation.
AB  - Chronic inflammatory diseases such as periodontitis have been associated with
      increased risk for various medical conditions including diabetes and
      cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram
      negative periodonto-pathogens, can induce the local accumulation of mononuclear
      cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix
      metalloproteinases (MMPs). This ultimately results in the destruction of
      periodontal connective tissues including alveolar bone. Curcumin is the principal
      dyestuff in the popular Indian spice turmeric and has significant regulatory
      effects on inflammatory mediators but is characterized by poor solubility and low
      bioactivity. Recently, we developed a series of chemically modified curcumins
      (CMCs) with increased solubility and zinc-binding activity, while retaining, or
      further enhancing, their therapeutic effects. In the current study, we
      demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin) has
      significant inhibitory effects, better than the parent compound curcumin, on
      proinflammatory cytokines and MMPs in in vitro, in cell culture, and in an animal
      model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its
      congeners may help to prevent tissue damage during various chronic inflammatory
      diseases including periodontitis and may reduce the risks of systemic diseases
      associated with this local disorder. 

PMID- 24453416
TI  - Alliin, a garlic (Allium sativum) compound, prevents LPS-induced inflammation in
      3T3-L1 adipocytes.
AB  - Garlic (Allium sativum L.) has been used to alleviate a variety of health
      problems due to its high content of organosulfur compounds and antioxidant
      activity. The main active component is alliin (S-allyl cysteine sulfoxide), a
      potent antioxidant with cardioprotective and neuroprotective actions. In
      addition, it helps to decrease serum levels of glucose, insulin, triglycerides,
      and uric acid, as well as insulin resistance, and reduces cytokine levels.
      However its potential anti-inflammatory effect is unknown. We examined the
      effects of alliin in lipopolysaccharide- (LPS-) stimulated 3T3-L1 adipocytes by
      RT-PCR, Western blot, and microarrays analysis of 22,000 genes. Incubation of
      cells for 24 h with 100 MUmol/L alliin prevented the increase in the expression
      of proinflammatory genes, IL-6, MCP-1, and Egr-1 in 3T3-L1 adipocytes exposed to
      100 ng/mL LPS for 1 h. Interestingly, the phosphorylation of ERK1/2, which is
      involved in LPS-induced inflammation in adipocytes, was decreased following
      alliin treatment. Furthermore, the gene expression profile by microarrays
      evidentiate an upregulation of genes involved in immune response and
      downregulation of genes related with cancer. The present results have shown that
      alliin is able to suppress the LPS inflammatory signals by generating an anti
      inflammatory gene expression profile and by modifying adipocyte metabolic
      profile.

PMID- 24453417
TI  - Erythrocyte shape abnormalities, membrane oxidative damage, and beta-actin
      alterations: an unrecognized triad in classical autism.
AB  - Autism spectrum disorders (ASDs) are a complex group of neurodevelopment
      disorders steadily rising in frequency and treatment refractory, where the search
      for biological markers is of paramount importance. Although red blood cells
      (RBCs) membrane lipidomics and rheological variables have been reported to be
      altered, with some suggestions indicating an increased lipid peroxidation in the
      erythrocyte membrane, to date no information exists on how the oxidative membrane
      damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in
      autism. Here, we investigated RBC morphology by scanning electron microscopy in
      patients with classical autism, that is, the predominant ASDs phenotype (age
      range: 6-26 years), nonautistic neurodevelopmental disorders (i.e., "positive
      controls"), and healthy controls (i.e., "negative controls"). A high percentage
      of altered RBCs shapes, predominantly elliptocytes, was observed in autistic
      patients, but not in both control groups. The RBCs altered morphology in autistic
      subjects was related to increased erythrocyte membrane F2-isoprostanes and 4
      hydroxynonenal protein adducts. In addition, an oxidative damage of the
      erythrocyte membrane beta-actin protein was evidenced. Therefore, the combination
      of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and
      beta-actin alterations constitutes a previously unrecognized triad in classical
      autism and provides new biological markers in the diagnostic workup of ASDs.

PMID- 24453418
TI  - A plasma proteomic approach in Rett syndrome: classical versus preserved speech
      variant.
AB  - Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by
      mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Although
      over 200 mutations types have been identified so far, nine of which the most
      frequent ones. A wide phenotypical heterogeneity is a well-known feature of the
      disease, with different clinical presentations, including the classical form and
      the preserved speech variant (PSV). Aim of the study was to unveil possible
      relationships between plasma proteome and phenotypic expression in two cases of
      familial RTT represented by two pairs of sisters, harbor the same MECP2 gene
      mutation while being dramatically discrepant in phenotype, that is, classical RTT
      versus PSV. Plasma proteome was analysed by 2-DE/MALDI-TOF MS. A significant
      overexpression of six proteins in the classical sisters was detected as compared
      to the PSV siblings. A total of five out of six (i.e., 83.3%) of the
      overexpressed proteins were well-known acute phase response (APR) proteins,
      including alpha-1-microglobulin, haptoglobin, fibrinogen beta chain, alpha-1
      antitrypsin, and complement C3. Therefore, the examined RTT siblings pairs proved
      to be an important benchmark model to test the molecular basis of phenotypical
      expression variability and to identify potential therapeutic targets of the
      disease. 

PMID- 24453419
TI  - Enhanced inflammatory activity of endometriotic lesions from the rectovaginal
      septum.
AB  - Endometriosis is characterised by the growth of ectopic lesions at multiple
      locations outside the uterine cavity and may be considered a collection of
      distinct but related conditions. The exact aetiology of endometriosis is still
      not clear although a role for inflammation is increasingly accepted. We therefore
      investigated the inflammatory activity of eutopic tissue and that of the matching
      ectopic lesions from different locations by measuring the genetic expression of
      inflammatory chemokines and cytokines. The gene expression in matching eutopic
      and ectopic tissue was compared, as was the gene expression in lesions from
      different locations. A significantly higher mRNA expression of the chemokines ENA
      78 and RANTES and the cytokines IL-6 and TNF alpha was observed in endometriotic
      lesions of the rectovaginal septum (RVS) compared to that of matching eutopic
      tissue. Comparisons across lesion locations showed a significantly higher
      expression of IL-6 and TNF alpha in the RVS compared to lesions from either the
      ovaries or the peritoneum. These results show that the production of some
      inflammatory chemokines and cytokines is significantly increased in the ectopic
      endometrial tissue compared to matching eutopic tissue. Furthermore, IL-6 and TNF
      alpha are produced in significantly higher quantities in RVS lesions compared to
      other lesions. 

PMID- 24453420
TI  - Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting
      intrinsic pathway of apoptosis and autophagy.
AB  - BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a pivotal clinical
      problem occurring in many clinical conditions such as transplantation, trauma,
      and hepatic failure after hemorrhagic shock. Apoptosis and autophagy have been
      shown to contribute to cell death in hepatic I/R injury. Ethyl pyruvate, a stable
      and simple lipophilic ester, has been shown to have anti-inflammatory properties.
      In this study, the purpose is to explore both the effect of ethyl pyruvate on
      hepatic I/R injury and regulation of intrinsic pathway of apoptosis and
      autophagy. METHODS: Three doses of ethyl pyruvate (20 mg/kg, 40 mg/kg, and 80
      mg/kg) were administered 1 h before a model of segmental (70%) hepatic warm
      ischemia was established in Balb/c mice. All serum and liver tissues were
      obtained at three different time points (4 h, 8 h, and 16 h). RESULTS: Alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and pathological
      features were significantly ameliorated by ethyl pyruvate (80 mg/kg). The
      expression of Bcl-2, Bax, Beclin-1, and LC3, which play an important role in the
      regulation of intrinsic pathway of apoptosis and autophagy, was also obviously
      decreased by ethyl pyruvate (80 mg/kg). Furthermore, ethyl pyruvate inhibited the
      HMGB1/TLR4/ NF-kappab axis and the release of cytokines (TNF-alpha and IL-6).
      CONCLUSION: Our results showed that ethyl pyruvate might attenuate to hepatic I/R
      injury by inhibiting intrinsic pathway of apoptosis and autophagy, mediated
      partly through downregulation of HMGB1/TLR4/ NF-kappab axis and the competitive
      interaction with Beclin-1 of HMGB1.

PMID- 24453421
TI  - TNF and TNF receptor superfamily members in HIV infection: new cellular targets
      for therapy?
AB  - Tumor necrosis factor (TNF) and TNF receptors (TNFR) superfamily members are
      engaged in diverse cellular phenomena such as cellular proliferation,
      morphogenesis, apoptosis, inflammation, and immune regulation. Their role in
      regulating viral infections has been well documented. Viruses have evolved with
      numerous strategies to interfere with TNF-mediated signaling indicating the
      importance of TNF and TNFR superfamily in viral pathogenesis. Recent research
      reports suggest that TNF and TNFRs play an important role in the pathogenesis of
      HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with
      TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of
      HIV infection, the use of TNF inhibitors can have significant impact on HIV
      disease progression. In this review, we will describe how HIV infection is
      modulated by signaling mediated through members of TNF and TNFR superfamily and
      in turn how these latter could be targeted by HIV proteins. Finally, we will
      discuss the emerging therapeutics options based on modulation of TNF activity
      that could ultimately lead to the cure of HIV-infected patients. 

PMID- 24453423
TI  - Marked independent relationship between circulating interleukin-6 concentrations
      and endothelial activation in rheumatoid arthritis.
AB  - We examined the potential impact of conventional compared with nonconventional
      cardiovascular risk factors including interleukin-6 levels on endothelial
      activation in RA. Circulating soluble E-selectin, vascular cell adhesion molecule
      1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1
      concentrations were measured in 217 African patients (112 black and 105 white)
      with RA. In comprehensive confounder adjusted mixed regression models, 5
      conventional and 4 nonconventional cardiovascular risk factors were associated (P
      = 0.05 to <0.0001) with endothelial activation. Interleukin-6 was the only risk
      factor related to each endothelial activation molecule and independently
      contributed by 18% and significantly more than other risk factors to the
      variation in overall endothelial activation as estimated by an SD (z) score of
      endothelial activation molecule concentrations. The independent interleukin-6
      overall endothelial activation relationships were reproduced in various
      subgroups. Interleukin-6 concentrations relate consistently, markedly, and to a
      larger extent than other cardiovascular risk factors to endothelial activation in
      RA. Assessment of interleukin-6 concentrations may enhance cardiovascular risk
      stratification in RA. 

PMID- 24453422
TI  - Overview of community-acquired pneumonia and the role of inflammatory mechanisms
      in the immunopathogenesis of severe pneumococcal disease.
AB  - Community-acquired pneumonia (CAP) remains a leading cause of morbidity and
      mortality among the infectious diseases. Despite the implementation of national
      pneumococcal polyvalent vaccine-based immunisation strategies targeted at high
      risk groups, Streptococcus pneumoniae (the pneumococcus) remains the most common
      cause of CAP. Notwithstanding the HIV pandemic, major challenges confronting the
      control of CAP include the range of bacterial and viral pathogens causing this
      condition, the ever-increasing problem of antibiotic resistance worldwide, and
      increased vulnerability associated with steadily aging populations in developed
      countries. These and other risk factors, as well as diagnostic strategies, are
      covered in the first section of this review. Thereafter, the review is focused on
      the pneumococcus, specifically the major virulence factors of this microbial
      pathogen and their role in triggering overexuberant inflammatory responses which
      contribute to the immunopathogenesis of invasive disease. The final section of
      the review is devoted to a consideration of pharmacological, anti-inflammatory
      strategies with adjunctive potential in the antimicrobial chemotherapy of CAP.
      This is focused on macrolides, corticosteroids, and statins with respect to their
      modes of anti-inflammatory action, current status, and limitations. 

PMID- 24453424
TI  - Long-term leukocyte filtration should be avoided during extracorporeal
      circulation.
AB  - Filtration during extracorporeal circulation (ECC) not only removes but also
      activates leukocytes; therefore, long-term leukocyte filtration may cause adverse
      effects. In the present study, we tested this hypothesis by priming ECC with 300
      mL of canine blood and examining filtration effects in 3 groups (n = 6 each)
      during 60 min ECC. In the control group (Group C) blood was filtrated with an
      arterial filter for 60 min; in long-term (Group L) and short-term (Group S)
      groups, blood was filtrated with a leukocyte filter for 60 and 5 min. We found
      that about 90% of leukocytes were removed after 5 min of filtration in both
      Groups L and S. Although leukocyte count continued to reduce, mean fluorescent
      intensities of CD11/CD18, free hemoglobin, and neutrophil elastase increased in
      Group L and were higher than those in Groups C and S at 60 min. Leukocyte
      rupture, cytoplasmic leakage, and circulating naked nuclei were also found in
      Group L. The data support our hypothesis that long-term filtration can induce
      inflammation and lead to leukocyte destruction.

PMID- 24453425
TI  - Circulating Th22 and Th9 levels in patients with acute coronary syndrome.
AB  - BACKGROUND: CD4+ T helper (Th) cells play critical roles in the development and
      progression of atherosclerosis and the onset of acute coronary syndromes (ACS,
      including acute myocardial infarction (AMI) and unstable angina pectoris (UAP)).
      In addition to Th1, Th2, and Th17 cells, Th22 and Th9 subsets have been
      identified in humans. In the present study, we investigated whether Th22 cells
      and Th9 cells are involved in the onset of ACS. METHODS: The frequencies of Th22
      and Th9 cells were detected using a flow cytometric analysis and their related
      cytokine and transcription factor were measured in the AMI, UAP, stable angina
      pectoris (SAP), and control groups. RESULTS: The results revealed a significant
      increase in the peripheral Th22 number, AHR expression, and IL-22 levels in
      patients with ACS compared with those in the SAP and control groups. Although
      there was no difference in the peripheral Th9 number among the four groups, the
      PU.1 expression and IL-9 levels were significantly increased in patients with ACS
      compared with the SAP and control groups. CONCLUSIONS: Circulating Th22 and Th9
      type responses may play a potential role in the onset of ACS symptom.

PMID- 24453426
TI  - Modulation of conjunctival goblet cell function by inflammatory cytokines.
AB  - Ocular surface inflammation associated with Sjogren's syndrome is characterized
      by a loss of secretory function and alteration in numbers of mucin secreting
      goblet cells. Such changes are a prominent feature of ocular surface inflammatory
      diseases and are attributed to inflammation; however, the exact effect of the
      inflammatory cytokines on conjunctival goblet cell function remains largely
      unknown. In this study, we developed a primary culture of mouse goblet cells from
      conjunctival tissue and evaluated the effects on their function by inflammatory
      cytokines detected in the conjunctiva of mouse model of Sjogren's syndrome
      (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was
      primarily induced by TNF-alpha and IFN-gamma. These two cytokines also inhibited
      mucin secretion by goblet cells in response to cholinergic stimulation, whereas
      IL-6 enhanced such secretion. No changes in secretory response were detected in
      the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in
      response to all the tested cytokines with the greatest response to IL-13 followed
      by IL-6. Our results therefore reveal that inflammatory cytokines expressed in
      the conjunctiva during an ocular surface disease directly disrupt conjunctival
      goblet cell functions, compromising the protective function of tears, thereby
      contributing to ocular surface damage.

PMID- 24453427
TI  - Hmgb1-IL-23-IL-17-IL-6-Stat3 axis promotes tumor growth in murine models of
      melanoma.
AB  - In order to understand how tumor cells can escape immune surveillance mechanisms
      and thus develop antitumor therapies, it is critically important to investigate
      the mechanisms by which the immune system interacts with the tumor
      microenvironment. In our current study, IL-17 deficiency results in reduced
      melanoma tumor size, diminished numbers of proliferating cells and blood vessels,
      and decreased percentage of CD11b(+)Gr-1(+) MDSCs in tumor tissues. IL-17
      promotes IL-6 induction and Stat3 activation. Treatment of Stat3 inhibitor WP1066
      in B16-F10 tumor cells inoculated wild-type mice inhibits tumor growth.
      Additional administration of recombinant IL-6 into B16-F10 tumor-bearing IL-17(-/
      ) mice results in markedly increased tumor size and p-Stat3 expression, whereas
      additional recombinant IL-17 administration into B16-F10 tumor-bearing wild-type
      mice treated with anti-IL-6 mAb does not significantly alter the tumor growth and
      p-Stat3 expression. In our further study, blockade of Hmgb1-RAGE pathway inhibits
      melanoma tumor growth and reduces production of IL-23 and IL-17. All these data
      suggest that Hmgb1-IL-23-IL-17-IL-6-Stat3 axis plays a pivotal role in tumor
      development in murine models of melanoma, and blocking any portion of this axis
      will attenuate melanoma tumor growth. 

PMID- 24453430
TI  - Blockade of 4-1BB and 4-1BBL interaction reduces obesity-induced skeletal muscle
      inflammation.
AB  - Obesity-induced skeletal muscle inflammation is characterized by increased
      macrophage infiltration and inflammatory cytokine production. In this study, we
      investigated whether 4-1BB, a member of the TNF receptor superfamily (TNFRSF9)
      that provides inflammatory signals, participates in obesity-induced skeletal
      muscle inflammation. Expression of the 4-1BB gene, accompanied by increased
      levels of inflammatory cytokines, was markedly upregulated in the skeletal muscle
      of obese mice fed a high-fat diet, in muscle cells treated with obesity factors,
      and in cocultured muscle cells/macrophages. In vitro stimulation of 4-1BB with
      agonistic antibody increased inflammatory cytokine levels in TNFalpha-pretreated
      muscle cells, and this effect was absent in cells derived from 4-1BB-deficient
      mice. Conversely, disruption of the interaction between 4-1BB and its ligand (4
      1BBL) with blocking antibody decreased the release of inflammatory cytokines from
      cocultured muscle cells/macrophages. Moreover, deficiency of 4-1BB markedly
      reduced macrophage infiltration and inflammatory cytokine production in the
      skeletal muscle of mice fed a high-fat diet. These findings indicate that 4-1BB
      mediates the inflammatory responses in obese skeletal muscle by interacting with
      its ligand 4-1BBL on macrophages. Therefore, 4-1BB and 4-1BBL may be useful
      targets for prevention of obesity-induced inflammation in skeletal muscle. 

PMID- 24453428
TI  - Alcohol-induced liver injury is modulated by Nlrp3 and Nlrc4 inflammasomes in
      mice.
AB  - Alcoholic liver disease (ALD) is characterized by increased hepatic lipid
      accumulation (steatosis) and inflammation with increased expression of
      proinflammatory cytokines. Two of these cytokines, interleukin-1 beta (IL-1 beta
      ) and IL-18, require activation of caspase-1 via members of the NOD-like receptor
      (NLR) family. These NLRs form an inflammasome that is activated by pathogens and
      signals released through local tissue injury or death. NLR family pyrin domain
      containing 3 (Nlrp3) and NLR family CARD domain containing protein 4 (Nlrc4) have
      been studied minimally for their role in the development of ALD. Using mice with
      gene targeted deletions for Nlrp3 (Nlrp3(-/-)) and Nlrc4 (Nlrc4(-/-)), we
      analyzed the response to chronic alcohol consumption. We found that Nlrp3(-/-)
      mice have more severe liver injury with higher plasma alanine aminotransferase
      (ALT) levels, increased activation of IL-18, and reduced activation of IL-1B. In
      contrast, the Nlrc4(-/-) mice had similar alcohol-induced liver injury compared
      to C57BL/6J (B6) mice but had greatly reduced activation of IL-1 beta . This
      suggests that Nlrp3 and Nlrc4 inflammasomes activate IL-1 beta and IL-18 via
      caspase-1 in a differential manner. We conclude that the Nlrp3 inflammasome is
      protective during alcohol-induced liver injury. 

PMID- 24453429
TI  - S100A8 and S100A9: DAMPs at the crossroads between innate immunity, traditional
      risk factors, and cardiovascular disease.
AB  - Amplification of innate immune responses by endogenous danger-associated
      molecular patterns (DAMPs) promotes inflammation. The involvement of S100A8 and
      S100A9, DAMPs belonging to the S100 calgranulin family, in the pathogenesis of
      cardiovascular disease is attracting an increasing amount of interest. S100A8 and
      S100A9 (also termed MRP8 and MRP14) preferentially form the S100A8/A9 heterodimer
      (MRP8/14 or calprotectin) and are constitutively expressed in myeloid cells. The
      levels of circulating S100A8/A9 in humans strongly correlate to blood neutrophil
      counts and are increased by traditional cardiovascular risk factors such as
      smoking, obesity, hyperglycemia, and dyslipidemia. S100A8/A9 is an endogenous
      ligand of toll-like receptor 4 (TLR4) and of the receptor for advanced glycation
      end products (RAGE) and has been shown to promote atherogenesis in mice. In
      humans, S100A8/A9 correlates with the extent of coronary and carotid
      atherosclerosis and with a vulnerable plaque phenotype. S100A8/A9 is locally
      released following myocardial infarction and amplifies the inflammatory responses
      associated with myocardial ischemia/reperfusion injury. Elevated plasma levels of
      S100A8/A9 are associated with increased risk of future coronary events in healthy
      individuals and in myocardial infarction survivors. Thus, S100A8/A9 might
      represent a useful biomarker and therapeutic target in cardiovascular disease.
      Importantly, S100A8/A9 blockers have been developed and are approved for clinical
      testing. 

PMID- 24453431
TI  - The role of T cell immunoglobulin mucin domains 1 and 4 in a herpes simplex virus
      induced Behcet's disease mouse model.
AB  - The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and
      tolerance. TIM-1 plays an important role in the regulation of immune responses
      and the development of autoimmune diseases. TIM-4 is a natural ligand of TIM-1,
      and the interaction of TIM-1 and TIM-4 is involved in the regulation of T helper
      (Th) cell responses and modulation of the Th1/Th2 cytokine balance. Behcet's
      disease (BD) is a chronic, multisystemic inflammatory disorder with arthritic,
      intestinal, mucocutaneous, ocular, vascular, and central nervous system
      involvement. Tim-1 expression was lower in a herpes simplex virus-induced BD
      mouse model compared to that in asymptomatic BD normal (BDN) mice. Tim-4
      expression was higher in BD mice than that in BDN mice. In this study, we
      investigated the Tim expression in a BD mouse model with BD-like symptoms. Tim-1
      and Tim-4 expression was regulated by an expression vector or siRNA injected into
      the BD mouse model. The Tim-1 vector injected into BD mice resulted in changes in
      BD-like symptoms and decreased the severity score. Treatment with Tim-4 siRNA
      also improved BD-like symptoms and decreased the severity score accompanied by
      upregulation of regulatory T cells. We showed that regulating Tim-1 or Tim-4
      affected BD-like symptoms in mice. 

PMID- 24453434
TI  - Greetings from bangalore, India.

PMID- 24453433
TI  - Inference for Seemingly Unrelated Varying-Coefficient Nonparametric Regression
      Models.
AB  - This paper is concerned with the inference of seemingly unrelated (SU) varying
      coefficient nonparametric regression models. We propose an estimation for the
      unknown coefficient functions, which is an extension of the two-stage procedure
      proposed by Linton, et al. (2004) in the longitudinal data framework where they
      focused on purely nonparametric regression. We show the resulted estimators are
      asymptotically normal and more efficient than those based on only the individual
      regression equation even when the error covariance matrix is homogeneous. Another
      focus of this paper is to extend the generalized likelihood ratio technique
      developed by Fan, Zhang and Zhang (2001) for testing the goodness of fit of
      models to the setting of SU regression. A wild block bootstrap based method is
      used to compute p-value of the test. Some simulation studies are given in support
      of the asymptotics. A real data set from an ongoing environmental epidemiologic
      study is used to illustrate the proposed procedures.

PMID- 24453435
TI  - Address by President, ISPCD.

PMID- 24453432
TI  - Ubiquitous transgenic overexpression of C-C chemokine ligand 2: a model to assess
      the combined effect of high energy intake and continuous low-grade inflammation.
AB  - Excessive energy management leads to low-grade, chronic inflammation, which is a
      significant factor predicting noncommunicable diseases. In turn, inflammation,
      oxidation, and metabolism are associated with the course of these diseases;
      mitochondrial dysfunction seems to be at the crossroads of mutual relationships.
      The migration of immune cells during inflammation is governed by the interaction
      between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine
      ligand 2 (CCL2), have a variety of additional functions that are involved in the
      maintenance of normal metabolism. It is our hypothesis that a ubiquitous and
      continuous secretion of CCL2 may represent an animal model of low-grade chronic
      inflammation that, in the presence of an energy surplus, could help to ascertain
      the afore-mentioned relationships and/or to search for specific therapeutic
      approaches. Here, we present preliminary data on a mouse model created by using
      targeted gene knock-in technology to integrate an additional copy of the CCl2
      gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination
      in embryonic stem cells. Short-term dietary manipulations were assessed and the
      findings include metabolic disturbances, premature death, and the manipulation of
      macrophage plasticity and autophagy. These results raise a number of mechanistic
      questions for future study. 

PMID- 24453437
TI  - Scope of Clinical research in Dentistry.

PMID- 24453436
TI  - "Publish or perish" applied current sketch in dental academia.

PMID- 24453438
TI  - Association of oral health related quality of life with dental anxiety and
      depression along with general health among people of Bhopal district, Madhya
      Pradesh.
AB  - BACKGROUND: To associate oral health related quality of life with dental anxiety
      and depression along with general health among people of Bhopal district, Madhya
      Pradesh. MATERIALS & METHODS: A cross sectional questionnaires based survey was
      conducted among the subjects of Bhopal district, Madhya Pradesh. The survey was
      carried among 101 subjects aging from 20-40 years. Subjects under investigation
      were belonging to various occupations. They were assigned a questionnaire.
      Questionnaire consisted of four parts, first part consists of socio-demographic
      data along with dental visiting habits, second part has OHqOL-questionnaire,
      third part has general health (sf-12) and fourth part has hospital anxiety and
      depression questionnaire. Questionnaire was used for assessment of OHqOL. It
      consists of 16 questions which takes into account both effect and impact of oral
      health on quality of life. Dental anxiety and depression was measured by Hospital
      Anxiety and Depression Scale. Each question was provided with four options and
      numbering ranging from 0-3. For general health consideration sf-12 v2 was being
      used, which calculates two values PCS and MCS giving result in percentage.
      RESULTS: A large proportion of respondent perceived oral health as having an
      enhanced effect on their quality of life in all three aspects that is general
      health, social and psychological. This is in stark contrast to other studies,
      where only physical aspects of oral health were more frequently considered to
      have the greatest overall impact of life quality compared with items relating to
      social, psychological and general health aspects. CONCLUSION: Gender variations
      were not apparent in the study. Both genders were likely to perceive oral health
      as it is impacting strongly on their quality of life. No significant gender
      variations are seen. But both have specific oral health needs and are most likely
      to utilize dental services which may be the key in understanding oral health
      behavior, including dental attendance patterns. How to cite this article: Shet
      RG, Jain G, Maroli S, Srivastava KJ, Kasina SP, Shwetha GS. Association of oral
      health related quality of life with dental anxiety and depression along with
      general health among people of Bhopal district, Madhya Pradesh. J Int Oral Health
      2013; 5(6):1-8 .

PMID- 24453439
TI  - Fracture strength of endodontically treated premolars: An In-vitro evaluation.
AB  - BACKGROUND: The aim of this study is to measure the invitro fracture strength of
      endodontically treated maxillary premolars restored with silver amalgam,
      composite resins and bonded amalgam. MATERIALS & METHODS: Sixty mature maxillary
      premolars free of caries, restoration or fracture extracted for orthodontic
      purpose or periodontal reasons were selected. The teeth were randomly divided
      into six groups of 10 teeth each. Group I: Intact teeth, Group II: Access opening
      only, Group III: Standard MOD cavity preparation + superimposed endodontic access
      (Unrestored). In Group IV, Group V & Group VI preparation was done as in Group
      III and they were restored with amalgam, bonded amalgam and composite resins
      respectively. All the teeth were thermo cycled and were mounted on custom made
      rings and the fracture strength was calculated with an Instron testing machine
      and the results were analysed statistically. RESULTS: Group I showed the highest
      fracture resistance followed by Group II . The difference in the values between
      the two groups were not significant. Group III showed the lowest fracture
      resistance the decrease in fracture strength was highly statistically significant
      when compared to all other groups investigated in the present study. Fracture
      strength of teeth restored with Group IV, Group V, Group VI did not differ
      significantly from each other. CONCLUSION: Fracture strength of intact natural
      teeth was superior to all the teeth tested in the study. Fracture strength of
      endodontically treated teeth restored with conventional amalgam, bonded amalgam
      and composite resin did not differ significantly from each other. Bonding of
      restorations to tooth structure has failed to bring about any improvement in the
      strength of the teeth tested. How to cite this article: Pradeep PR, Kumar VC,
      Bantwal SR, Gulati GS. Fracture strength of endodontically treated premolars: An
      In-vitro evaluation. J Int Oral Health 2013; 5(6):9-17 .

PMID- 24453440
TI  - Correlation of general anxiety and dental anxiety in children aged 3 to 5 years:
      A clinical survey.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of dental
      anxiety in a group of children aged 3 to 5 years and to explore the relationships
      between dental anxiety and general fearful nature of the child. MATERIALS &
      METHODS: A total of 250 children were selected for the study after due selection
      via inclusion criteria. Pre-school anxiety scale by Spence and Rapee (1999) was
      used to assess the general fear of the child and was filled by the parent during
      the first visit. Venham's anxiety scale was used to assess the dental anxiety
      which was seen during routine dental examination of the child on his first visit.
      RESULTS: The results were statistically analyzed using Chi square test and Karl
      Pearson coefficient of correlation. CONCLUSION: It was concluded that 24% of
      children showed association between high level of dental anxiety and high level
      of general fear; 56% of children also exhibited high level of dental anxiety with
      moderate score of general fear and 20% of children exhibited positive correlation
      between low level of dental anxiety and fear. How to cite this article: Nigam AG,
      Marwah N, Goenka P, Chaudhry A. Correlation of general anxiety and dental anxiety
      in children aged 3 to 5 years: A clinical survey. J Int Oral Health 2013;5(6):18
      24 .

PMID- 24453441
TI  - Annexin v - affinity assay - apoptosis detection system in granular cell
      ameloblastoma.
AB  - BACKGROUND: The aim of the study is to detect apoptosis in granular cell
      ameloblastoma by annexin v affinity assay, a novel technique. MATERIALS &
      METHODS: Excitional biopsy of two patients with granular cell ameloblastoma were
      fixed in buffered formalin and later embedded in paraffin wax. Blocks were sliced
      into 3m thick sections for routine histological and subsequent
      immunohistochemical examinations. For electron microscopic examination tissues
      were fixed in 2.5% glutaraldehyde.electron microscopic examination was carried
      out to find the nature of granularity in granular cell ameloblastoma which was
      finally confirmed by annexin v technique. RESULTS: Annexin v is a sensitive
      marker to detect early apoptosis. Fluorescence in granular cell clusters showed
      that apoptotic cell death is higher in granular cells. Both early and late events
      of apoptosis were identified in annexin v staining and electron microscopic study
      respectively. CONCLUSION: Our study confirms that increased apoptotic cell death
      and subsequent phagocytosis is responsible for granular appearance of cells in
      granular cell ameloblastoma compared with that of conventional ameloblastoma. How
      to cite this article: Balaji N, Devy AS, Sumathi MK, Vidyalakshmi S, Kumar GS,
      D'Silva S. Annexin V - Affinity Assay - Apoptosis Detection System in Granular
      Cell Ameloblastoma. J Int Oral Health 2013; 5(6):25-30 .

PMID- 24453442
TI  - Dento-Alveolar Distraction Osteogenesis for rapid Orthodontic Canine Retraction.
AB  - BACKGROUND: The objectives of this study were to evaluate the rate of canine
      distalization by segmental alveolar distraction method in first premolar
      extraction cases, to evaluate the displacement of the canine and first molar
      teeth, to assess the effects of the procedure on the pulpal vitality of the
      canines, and to determine the amount of root resorption in retracted canines.
      MATERIALS & METHODS: The sample of the study consisted of 20 teeth in 7 patients
      (five females and two males, mean age 18.5 years). After the osteotomy procedure
      distractor was fixed. After 3 days of consolidation period, the distractor was
      activated 3 quarter turns per day(0.75 mm/day) till the canines comes in contact
      with second premolar. An electrical vitality test was applied before and after
      the distraction procedure and during the follow-up period. RESULTS: The mean
      distal retraction of canines was 7.262 +/- 0.4864 mm. The distal displacement of
      the canine was mainly a combination of tipping and translation. The mean
      distraction procedure was completed in 14.60 +/-1.536 days. The duration of
      retraction was less for mandibular canine compared to maxillary canine. The mean
      posterior anchorage loss was mean 0.50+/-0.688 mm. The amount of root resorption
      that occurred during distraction was clinically insignificant. None of the teeth
      reacted negatively to the electrical vitality test that was performed 6 months
      after the completion of the distraction procedure. There was no clinical sign of
      discoloration or pulpal pain in any tooth. CONCLUSION: With dentoalveolar
      distraction, as canines can be fully retracted in 12 to 16 days, the non
      compliance patients, patients with root-shape malformations, periodontal
      problems, or ankylosed teeth will benefit from this technique. The anchorage
      teeth can withstand the retraction forces better with no anchorage loss, and
      without clinical or radiographic evidence of root resorption, ankylosis,
      periodontal problems, and soft tissue dehiscence. This technique reduces
      orthodontic treatment duration by 6 to 9 months in patients who need extraction,
      with no need for any sort of anchorage reinforcement. How to cite this article:
      Kumar N, Prashantha GS, Raikar S, Ranganath K, Mathew S, Nambiar S. Dento
      Alveolar Distraction Osteogenesis for rapid Orthodontic Canine Retraction. J Int
      Oral Health 2013; 5(6):31-41 .

PMID- 24453443
TI  - Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic
      Odontogenic Cysts - An immunohistochemical study.
AB  - BACKGROUND: Calretinin a 29-kDa calcium binding protein is expressed widely in
      normal human tissue and tumours including amelobastoma. The objective of this
      study was to determine calretinin expression in heamatoxylin and eosin diagnosed
      cases of ameloblastoma and non-neoplastic odontogenic cysts. MATERIALS & METHODS:
      The lining epithelium in 3 cases of radicular cysts, 5 cases of odontogenic
      keratocysts, 5 cases of dentigerous cysts and 11 cases of ameloblastomas were
      examined for expression of calretinin. RESULTS: No positive epithelial staining
      was observed in radicular and dentigerous cysts. In comparison, however 100% of
      cases of ameloblastomas and 40% of cases of odontogenic karatocysts showed
      positive calretinin expression. CONCLUSION: Calretinin may be a specific
      immunohistochemical marker for ameloblastoma. If there is any possible relation
      between calretinin expression and neural origin of the odontogenic epithelium and
      its neoplastic transformation and if calretinin could be used as an early marker
      to predict the tendency of neoplastic change of odontogenic epithelium could be
      answered through further researches. How to cite this article: D'Silva S, Sumathi
      MK, Balaji N, Shetty NK, Pramod KM, Cheeramelil J. Evaluation of Calretinin
      expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An
      immunohistochemical study. J Int Oral Health 2013; 5(6):42-8 .

PMID- 24453444
TI  - Prevalence of Malocclusion among 6 to 10 Year old Nalgonda School Children.
AB  - BACKGROUND: To evaluate the prevalence of malocclusion among 6 to 10 year old
      children of Nalgonda District. MATERIALS & METHODS: A total of 3000 children were
      examined, out of which 2135 children (1009 boys and 1126 girls) who fulfilled the
      inclusion criteria were included. The selected sample was examined for Class I,
      Class II, Class III molar relationship, lower anterior crowding, cross bite
      (anterior and posterior), open bite, and pseudo class III [edge to edge bite]
      discrepancies after obtaining the written consent from the concerned school
      authorities. The collected data was tabulated and statistically analysed using
      chi-square test. RESULTS: Among the selected sample, 648 (30.35%) children had
      minor tooth alignment discrepancies. Angle's Class I molar relation with and
      without minor discrepancies was observed in 78.6%, Class II in 13.9%, Class III
      in 7.8% of the subjects surveyed. Lower anterior crowding in 11.8%, anterior
      cross bite in 4.5%, posterior cross bite in 3.75%, openbite in 3% and Pseudo
      class III [edge to edge] in 5.97% was noticed among the studied population. There
      was no statistical significant difference observed gender wise. CONCLUSION: In
      the current study, 52% of the studied population had malocclusion with a higher
      prevalence of Angle's Class I molar relation with lower anterior crowding. How to
      cite this article: Reddy ER, Manjula M, Sreelakshmi N, Rani ST, Aduri R, Patil
      BD. Prevalence of Malocclusion among 6 to 10 Year old Nalgonda School Children. J
      Int Oral Health 2013; 5(6):49-54 .

PMID- 24453445
TI  - Dental Aesthetic Index of school students in Telangana region - An
      epidemiological study.
AB  - BACKGROUND: Malocclusion should be identified at its earliest before it produces
      any detrimental effects. The objective of this study is to evaluate the
      orthodontic status and treatment need of school children in Telangana region,
      Andhra Pradesh, using Dental Aesthetic Index. MATERIALS & METHODS: One thousand
      children in the age group of 12 - 14 years who fulfilled the inclusion and
      exclusion criteria were considered. The demographic details of the students along
      with the information on the orthodontic status were collected using a predesigned
      questionnaire by a single orthodontist. The information on orthodontic status was
      obtained using Dentofacial Anomalies with the criteria of Dental Aesthetic Index
      (W H O Oral Health Assessment form 1997). RESULTS: RESULTS were subjected to
      ANOVA, Tukeys test and chi square test using SPSS, version 16. 86.1% of the
      subjects had DAI score of less than 25, suggesting 'no treatment'; 10% had DAI
      score of 26-30, suggesting 'elective treatment'; 3% had DAI score of 31-35,
      suggesting 'highly desirable treatment'; 0.9% had DAI score of >36, indicating
      'mandatory treatment'; Higher prevalence of malocclusion among females than
      males. CONCLUSION: It is necessary to identify this abnormality at its earliest
      before it produces detrimental effects. It is also essential to know the
      prevalence of malocclusion in any society, as it reveals the true extent of the
      problem and guides in overcoming it. The general public can, then, be educated on
      widespread occurrence of malocclusion and its deleterious effects, so that
      appropriate preventive and corrective measures can be instituted. How to cite
      this article: Anita G, Kumar GA, Reddy V, Reddy TP, Rao MS, Wankhade SB. Dental
      Aesthetic Index of school students in Telangana region - An epidemiological
      study. J Int Oral Health 2013; 5(6):55-60 .

PMID- 24453446
TI  - Comparison of the antibacterial efficiency of neem leaf extracts, grape seed
      extracts and 3% sodium hypochlorite against E. feacalis - An in vitro study.
AB  - BACKGROUND: E. faecalis is the predominant micro-organism recovered from root
      canal of the teeth where previous endodontic treatment has failed. Thorough
      debridement and complete elimination of micro-organisms are objectives of an
      effective endodontic treatment. For many years, intracanal irrigants have been
      used as an adjunct to enhance antimicrobial effect of cleaning and shaping in
      endodontics. The constant increase in antibiotic-resistant strains and side
      effects of synthetic drugs has promoted researchers to look for herbal
      alternatives. For thousands of years humans have sought to fortify their health
      and cure various illnesses with herbal remedies, but only few have been tried and
      tested to withstand modern scientific scrutiny. The present study was aimed to
      evaluate alternative, inexpensive simple and effective means of sanitization of
      the root canal systems. The antimicrobial efficacy of herbal alternatives as
      endodontic irrigants is evaluated and compared with the standard irrigant sodium
      hypochlorite. MATERIALS & METHODS: Neem leaf extracts, grape seed extracts, 3%
      Sodium hypochlorite, absolute ethanol, Enterococcus faecalis (ATCC 29212)
      cultures, Brain heart infusion media. The agar diffusion test was performed in
      brain heart infusion media and broth. The agar diffusion test was used to measure
      the zone of inhibition. RESULTS: Neem leaf extracts and grape seed extracts
      showed zones of inhibition suggesting that they had anti-microbial properties.
      Neem leaf extracts showed significantly greater zones of inhibition than 3%
      sodium hypochlorite. Also interestingly grape seed extracts showed zones of
      inhibition but were not as significant as of neem extracts. CONCLUSION: Under the
      limitations of this study, it was concluded that neem leaf extract has a
      significant antimicrobial effect against E. faecalis. Microbial inhibition
      potential of neem leaf extract observed in this study opens perspectives for its
      use as an intracanal medication. How to cite this article: Ghonmode WN, Balsaraf
      OD, Tambe VH, Saujanya KP, Patil AK, Kakde DD. Comparison of the antibacterial
      efficiency of neem leaf extracts, grape seed extracts and 3% sodium hypochlorite
      against E. feacalis - An in vitro study. J Int Oral Health 2013; 5(6):61-6 .

PMID- 24453447
TI  - Prevalence and self perception of Dental Fluorosis among 15 year old school
      children in Prakasham district of south India.
AB  - BACKGROUND: To assess the Prevalence and self perception of dental fluorosis
      among 15 - year old school children. MATERIALS & METHODS: A cross sectional study
      was conducted on 840, 15 - year old school children from 12 schools of Prakasam
      district. After taking informed consent from their parents or legal
      representatives, an interview was conducted using a pretested questionnaire to
      collect the data regarding self perception of dental fluorosis, dental behaviour,
      and source of water and diet and socio demographic characters. Oral examination
      was done under natural light to score Deans fluorosis index. Statistical test
      used was chisquare test. RESULTS: Study revealed that 82.04% of the study
      population were having dental fluorosis. Out of which only 42.3% were aware of
      the existing situations. 47.90% of boys are aware of dental fluorosis where as
      40.50% of girls are aware of dental fluorosis. Fluorosis score in relation to
      gender is not statistically significant (chisquare (8.796);p=0.117). CONCLUSION:
      Dental fluorosis is a public health problem in Kanigiri town. As there was no
      study conducted in Kanigiri town even though it is one of the severely affected
      area in our country. Active steps must be taken to De fluoridate the water before
      distribution to reduce the morbidity associated with dental fluorosis in this
      area. How to cite this article: Naidu GM, Rahamthullah SA, Kopuri RK, Kumar YA,
      Suman SV, Balaga RN. Prevalence and self perception of Dental Fluorosis among 15
      year old school children in Prakasham district of south India. J Int Oral Health
      2013; 5(6):67-71.

PMID- 24453448
TI  - Evaluation and correlation of serum lipid profile in oral and gastrointestinal
      cancer patients.
AB  - BACKGROUND: High or low cholesterol levels can be perturbing. High cholesterol
      levels in the blood are associated with increased risk of coronary heart disease
      whereas insinuation of decreased cholesterol levels remains imprecise. Present
      study is to evaluate any relationship between the serum lipid levels and the
      cancer. The purpose of this study is to evaluate the alteration of serum lipid
      profiles in untreated mucosal cancer patients. MATERIALS & METHODS: The study
      sample consisted of thirty subjects (Group I - 10 gastrointestinal cancer
      patients, Group II - 10 oral cancer patients and Group III - 10 controls).
      Fasting lipid profile of blood was evaluated using spectrophotometric kits, with
      CHOD PAP technique. The values obtained were then statistically analyzed using
      ANOVA and student 't' test. RESULTS: Between Group I and II, Group I
      comparatively showed more decrease in TC, TG, VLDL and increase in HDL & LDL. P
      value was significant in only TG. Between Group II and III, TC, HDL and LDL were
      decreased whereas TG and VLDL were increased in Group II when compared to Group
      III. TG, LDL, VLDL showed significant p values. Between Group I and III, the
      variables showed similar results as seen between Group II and III but only LDL
      showed significant p value. Among the three groups, only LDL showed significant p
      value (0.048). TC, TG, HDL and VLDL showed non - significant p values.
      CONCLUSION: Lower levels of lipid should arouse suspicion for cancer and
      necessary screening should be done. How to cite this article: Srinivas GV, Namala
      S, Ananthaneni A, Puneeth HK, Devi BS. Evaluation and Correlation of Serum Lipid
      Profile in Oral and Gastrointestinal Cancer Patients. J Int Oral Health 2013;
      5(6):72-7 .

PMID- 24453449
TI  - Evaluation of Patient's Personal Reasons and Experience with Orthodontic
      Treatment.
AB  - BACKGROUND: The objective of the study is to evaluate patient's personal reasons
      and experience with orthodontic treatment. Also to find the problems faced during
      the orthodontic procedure. MATERIALS & METHODS: A cross-sectional study was done
      using pretested questionnaire among 312 patients (178 - males and 134 - females)
      with a response rate of 85%. The overall mean age of the population was 21.34+/
      62 years. The data was collected on excel sheet and analyzed by SPSS 15.0
      software at p value 0.05 for the statistical significance. RESULTS: Half of the
      participants (52.4%) had undergone orthodontic procedure for straightening the
      teeth as they think that teeth are the important features that affect the facial
      profile. Around fifty percent judged themselves that they require this procedure.
      Most common problem faced by the participants during treatment was its longer
      duration (29.3%). Still 86.4% of them were satisfied with the treatment.
      CONCLUSION: The study concluded most of the subjects themselves noted that they
      are in need of orthodontic treatment in them. There were many problems faced
      during the procedure by the participants but still most of them were satisfied
      after the results. How to cite this article: Sharma S, Narkhede S, Sonawane S,
      Gangurde P. Evaluation of Patient's Personal Reasons and Experience with
      Orthodontic Treatment. J Int Oral Health 2013; 5(6):78-81 .

PMID- 24453450
TI  - Comparative evaluation of border molding, using two different techniques in
      maxillary edentulous arches - An in vivo study.
AB  - BACKGROUND: This study was undertaken to compare the retention between sectional
      border molding using low fusing greenstick compound and single step border
      molding using condensation silicone (putty) impression material in three stages-
      A. Immediately following border molding, B. After final impression and C. With
      the finished permanent denture base. MATERIALS & METHODS: In this study
      evaluation of retentive values of sectional border molding (Group I) (custom
      impression trays border molded with green stick compound ) and single step border
      molding (Group II) ( border molding with condensation silicone (putty) impression
      material ). In both techniques definitive wash impression were made with light
      body condensation silicone and permanent denture base with heat cure
      polymerization resin. RESULTS: Group II was significantly higher (mean=8011.43)
      than Group I (mean=5777.43) in test-A. The t-value (1.5883) infers that there was
      significant difference between Group I and Group II (p =0.15). Group I was
      significantly higher (mean=6718.57) than Group II (mean=5224.29) in test -B. The
      t-value (1.6909) infers that there was significant difference between Group I and
      Group II (p=0.17). Group II was higher (mean=4025.14) than Group I (mean=3835.07)
      in test -C. The t-value was 0.1239. But it was found to be statistically
      insignificant (p=0.005). CONCLUSION: Within the limitation of this clinical study
      border molding custom tray with low fusing green stick compound provided similar
      retention as compared to custom impression tray with condensation silicone in
      permanent denture base. How to cite this article: Yarapatineni R, Vilekar A,
      Kumar JP, Kumar GA, Aravind P, Kumar PA. Comparative evaluation of border
      molding, using two different techniques in maxillary edentulous arches - An in
      vivo study. J Int Oral Health 2013; 5(6):82-7 .

PMID- 24453451
TI  - Association of dentine hypersensitivity with different risk factors - a cross
      sectional study.
AB  - BACKGROUND: This study was done to assess the prevalence of Dentine
      hypersensitivity (DH) and its associated risk factors. MATERIALS & METHODS: This
      epidemiological study was done among patients coming to dental college regarding
      prevalence of DH. A self structured questionnaire along with clinical examination
      was done for assessment. Descriptive statistics were obtained and frequency
      distribution was calculated using Chi square test at p value <0.05. Stepwise
      multiple linear regression was also done to access frequency of DH with different
      factors. RESULTS: The study population was comprised of 655 participants with
      different age groups. Our study showed prevalence as 55% and it was more common
      among males. Similarly smokers and those who use hard tooth brush had more cases
      of DH. Step wise multiple linear regression showed that best predictor for DH was
      age followed by habit of smoking and type of tooth brush. Most aggravating
      factors were cold water (15.4%) and sweet foods (14.7%), whereas only 5% of the
      patients had it while brushing. CONCLUSION: A high level of dental
      hypersensitivity has been in this study and more common among males. A linear
      finding was shown with age, smoking and type of tooth brush. How to cite this
      article: Vijaya V, Sanjay V, Varghese RK, Ravuri R, Agarwal A. Association of
      Dentine Hypersensitivity with Different Risk Factors - A Cross Sectional Study. J
      Int Oral Health 2013;5(6):88-92 .

PMID- 24453452
TI  - Treatment of mandibular angle fracture with a 2mm, 3 dimensional rectangular grid
      compression miniplates: A prospective clinical study.
AB  - BACKGROUND: Surgical treatment of fracture mandible using an internal fixation
      has changed in the last decades to achieve the required rigidity, stability and
      immediate restoration of function. The aim of the study was to do a Prospective
      study of 10 patients to determine the efficacy of rectangular grid compression
      miniplates in mandibular fractures. MATERIALS & METHODS: This study was carried
      out using 2.0 rectangular grid compression miniplates and 8 mm multidirectional
      screws as a rigid internal fixation in 10 patients without post operative
      intermaxillary fixation (IMF). Follow up was done for period of 6 months.
      RESULTS: All fractures were healed with an absolute stability in post operative
      period. None of the patient complained of post operative difficulty in occlusion.
      CONCLUSION: Within the limits of this study, it can be concluded that rectangular
      grid compression miniplates was rigid, reliable and thus can be recommended for
      the treatment of mandibular angle fractures. How to cite this article: Mansuri S,
      Abdulkhayum AM, Gazal G, Hussain MA. Treatment of mandibular angle fracture with
      a 2mm, 3 dimensional rectangular grid compression miniplates: A prospective
      clinical study. J Int Oral Health 2013;5(6):93-100 .

PMID- 24453453
TI  - Effect of grape seed extracts on bond strength of bleached enamel using fifth and
      seventh generation bonding agents.
AB  - BACKGROUND: The objective of this in-vitro study was to evaluate the effect of
      grape seed extract (oligomericproanthocyanidin complexes [OPCs]) on the bond
      strength of composite resin to bleached enamel using 5th and 7th generations of
      bonding agents. MATERIALS & METHODS: Eighty maxillary central incisors were
      randomly assigned to four groups as follows: Group I (n=20): no bleaching
      (control); Group II (n=20): bleaching with 38% hydrogen peroxide gel, without the
      use of an antioxidant; Group III (n=20): bleaching followed by the use of 10%
      sodium ascorbate; Group IV (n=20) : bleaching followed by the use of 5%
      proanthocyanidin solution. All the four groups were further subdivided into two
      groups of ten teeth each depending on the adhesive system used in order to bond
      the resin composite to enamel surfaces. Subgroup A: 5th generation bonding agent
      and subgroup B : 7th generation bonding agent. Shear bond strength of the
      specimens was tested under universal testing machine. RESULTS: The shear bond
      strength values were observed to be significantly higher in teeth treated with
      10% sodium ascorbate and 5% proanthocyanidin as compared to the group in which no
      antioxidant was used. Also, bonding with 5th generation bonding agent resulted in
      significantly higher shear bond strength when compared to the 7th generation
      bonding agent. CONCLUSION: The use of grape seed extract as an antioxidant after
      bleaching significantly improves the bond strength of composite resin to bleached
      enamel. 5th generation bonding agents have higher shear bond strength of
      composite resin to enamel. How to cite this article: Abraham S, Ghonmode WN,
      Saujanya KP, Jaju N, Tambe VH, Yawalikar PP. Effect of grape seed extract on bond
      strength of bleached enamel using fifth and seventh generation bonding agents. J
      Int Oral Health 2013; 5(6):101-7 .

PMID- 24453454
TI  - Sterilizing Endodontic Files by four different sterilization methods to prevent
      cross-infection - An In-vitro Study.
AB  - BACKGROUND: Aim of the study was to compare 4 different methods of sterilizing
      endodontic files in dental practice. MATERIALS & METHODS: The present study was
      performed on 100 K-files, 21 mm long and of size 25. Of these, 20 files were
      taken as control group, and the remaining 80 files were divided into 4 groups of
      20 files each and they were tested for the efficacy of sterilization with
      different methods: Autoclave, glass bead, glutaraldehyde and CO2 laser. RESULTS:
      The study showed that the files sterilized by autoclave and lasers were
      completely sterile. Those sterilized by glass bead were 90% sterile and those
      with glutaraldehyde were 80% sterile. CONCLUSION: The study concluded that
      autoclave or laser could be used as a method of sterilization in clinical
      practice and in advanced clinics; laser can be used also as a chair side method
      of sterilization. How to cite this article: Raju TB, Garapati S, Agrawal R, Reddy
      S, Razdan A, Kumar SK. Sterilizing Endodontic Files by four different
      sterilization methods to prevent cross-infection - An In-vitro Study. J Int Oral
      Health 2013; 5(6):108-12 .

PMID- 24453455
TI  - Atraumatic extraction and immediate implant installation: The importance of
      maintaining the contour gingival tissues.
AB  - There is an accelerated resorption in the first six months after the extraction
      of the dental element, both horizontally and vertically. These clinical changes
      normally undertake the aesthetic result of prosthetic rehabilitation, and implant
      installation after the extraction can be a resource to decrease resorption. The
      clinical case described in this paper demonstrates a sequence of clinical
      atraumatic extraction, and then the Immediate installation provisionalization. It
      is concluded that when carefully indicated and planned, this technique can
      provide an immediate result promising with maintaining the tooth gingival
      contour. How to cite this article: Tavarez RR, Machado dos Reis WL, Rocha AT,
      Firoozmand LM, Bandeca MC, Tonetto MR, Malheiros AS. Atraumatic extraction and
      immediate implant installation: The importance of maintaining the contour
      gingival tissues. J Int Oral Health 2013; 5(6):113-8 . 

PMID- 24453456
TI  - Current advances in radiotherapy of head and neck malignancies.
AB  - Necessity is the mother of all inventions. This is also true in case of cancer
      therapy. With increasing incidence of head and neck malignancies, remarkable
      developments have been made towards cancer development and treatment which
      continues to be a major challenge. Approximately fifty percent of all cancer
      patients receive radiotherapy which contributes towards forty percent of curative
      treatment for cancer. New developments in radiation oncology have helped to
      improve outlook for patients and find more effective treatment. With the advent
      of new technologies, radiotherapy seems to be promising in patients with head and
      neck malignancies these advancements include Altered fractionation, Three
      dimensional conformal radiotherapy, Intensity-modulated radiotherapy, Image
      Guided Radiotherapy, Stereotactic radiation, Charged-particle radiotherapy, and
      Intraoperative radiotherapy. How to cite this article: Roopashri G, Baig M.
      Current advances in radiotherapy of head and neck malignancies. J Int Oral Health
      2013; 5(6):119-23 . 

PMID- 24453457
TI  - Invasive cervical resorption: a review.
AB  - Invasive cervical resorption is a relatively uncommon form of external root
      resorption exhibiting no external signs. The resorptive condition is often
      detected by routine radiographic examination. The clinical features vary from a
      small defect at the gingival margin to a pink coronal discoloration of the tooth
      crown resulting in ultimate cavitation of the overlying enamel which is painless
      unless pulpal or periodontal infection supervenes. Radiographic features of
      lesions vary from well-delineated to irregularly bordered mottled radiolucencies,
      and these can be confused with dental caries. A characteristic radiopaque line
      generally separates the image of the lesion from that of the root canal, because
      the pulp remains protected by a thin layer of predentin until late in the
      process. Histopathologically, the lesions contain fibrovascular tissue with
      resorbing clastic cells adjacent to the dentin surface. More advanced lesions
      display fibro-osseous characteristics with deposition of ectopic bonelike
      calcifications both within the resorbing tissue and directly on the dentin
      surface. How to cite this article: Kandalgaonkar SD, Gharat LA, Tupsakhare SD,
      Gabhane MH. Invasive Cervical Resorption: A Review. J Int Oral Health
      2013;5(6):124-30 . 

PMID- 24453458
TI  - A Spider like body in Keratocystic Odontogenic Tumor - A Paradoxical find.
AB  - Inclusion bodies are nuclear or cytoplasmic aggregates of proteins that may be
      formed due to infections or genetic disorders. Asteroid body is one such
      inclusion that is eosinophilic and spider like that are usually found in
      infections like sarcoidosis and sporotrichosis. Inclusions are usually
      pathognomonic of certain diseases and conditions, navigating the pathologist to
      arrive at a diagnosis. But, here we report an unusual finding of an asteroid body
      encountered in an inflamed keratocystic odontogenic tumor. How to cite this
      article: Patil S, Rao RS, Amrutha N. A Spider like body in Keratocystic
      Odontogenic Tumor - A Paradoxical find. J Int Oral Health 2013; 5(6):131-3 . 

PMID- 24453459
TI  - Medical emergencies in dental office.

PMID- 24453460
TI  - DINITROBENZENES STIMULATE ELECTRON FLUX WITHIN NEURONAL NITRIC OXIDE SYNTHASE IN
      THE ABSENCE OF CALMODULIN.
AB  - Efficient electron transfer and conversion of L-arginine to L-citrulline and
      nitric oxide (NO*) by neuronal nitric oxide synthase (nNOS) requires calmodulin
      (CaM) binding. The present study focused on electron transfer ability of resting
      state CaM-free nNOS in presence of dinitrobenzene isomers (DNBs). NADPH oxidation
      (NADPH ox ) and acetylated cytochrome-c reduction (AcCyt-cred ) catalyzed by nNOS
      and the CaM binding sequence-deficient nNOS reductase construct (nNOS-FP) were
      estimates of total electron flux and [Formula: see text] production,
      respectively. All the DNBs (o-, m-, p-) independently stimulated rates of NADPH
      ox by CaM-free nNOS and by nNOS-FP in isomer- and concentration-dependent manner.
      Blocking nNOS heme by imidazole or L-arginine did not affect CaM-free nNOS
      catalyzed NADPH ox stimulated by DNBs. This stimulated electron flux by DNBs did
      not support NO* formation by CaM-free nNOS. The DNBs, like FeCN, extract
      electrons from both FMN and FAD of the nNOS reductase domain. All three DNBs
      greatly stimulated nNOS and nNOS-FP catalyzed AcCyt-cred that was significantly
      inhibited by SOD demonstrating [Formula: see text] formation. Thus, in presence
      of DNBs, resting-state CaM-deficient nNOS efficiently transfers electrons
      generating [Formula: see text], inferring that additional metabolic roles for
      nNOS exist that are not yet explored.

PMID- 24453461
TI  - Evaluation of CLT1-(Gd-DTPA) for Cancer MR Molecular Imaging in a Mouse Breast
      Cancer Model.
AB  - A peptide targeted contrast agent, CLT1-(Gd-DTPA), was investigated for molecular
      imaging of fibrin-fibronectin complexes in tumor stroma with magnetic resonance
      imaging (MRI). The contrast agent was evaluated in female nude mice bearing MDA
      MB-231 human breast carcinoma xenografts on a Siemens 3T clinical scanner with a
      clinical agent Gd(DTPA-BMA) as a non-targeted control. CLT1-(Gd-DTPA)
      specifically bound to tumor tissue and resulted in significant tumor contrast
      enhancement at a dose of 0.05 mmol/kg for at least 60 minutes after injection. In
      contrast, a non-targeted contrast agent, Gd(DTPA-BMA), cleared rapidly from the
      body with little tumor enhancement after 30 minutes post-injection at a dose of
      0.1 mmol/kg. CLT1-(Gd-DTPA) had little non-specific binding in blood and normal
      tissues, including the liver and muscle, resulting in comparable non-specific
      enhancement in normal tissues as the control agent. The study has shown that CLT1
      (Gd-DTPA) can bind to the tumor tissue, resulting in significant tumor
      enhancement in a mouse breast cancer model. The targeted contrast agent has a
      potential for MR molecular imaging of breast cancer.

PMID- 24453462
TI  - Julian's Birth.
AB  - A grandmother of seven and childbirth educator shares her daughter's successful
      vaginal birth after cesarean (VBAC) birth story in Switzerland. 

PMID- 24453463
TI  - Major Survey Findings of Listening to Mothers(SM) III: Pregnancy and Birth:
      Report of the Third National U.S. Survey of Women's Childbearing Experiences.
AB  - To understand the experiences and views of childbearing women in the United
      States and trends over time, Childbirth Connection carried out the third national
      Listening to Mothers survey among 2,400 women who gave birth in U.S. hospitals to
      a single baby from mid-2011 to mid-2012 and could participate in English. Harris
      Interactive conducted the survey using a validated methodology that includes data
      weighting to ensure that results closely reflect the target population. Results
      of the initial survey describe experiences from before pregnancy through the
      early postpartum period, and were reported in Listening to Mothers III: Pregnancy
      and Birth. A follow-up survey directed to the same participants explored
      postpartum experiences, attitudes about maternity care, and some additional
      pregnancy and birth items. 

PMID- 24453464
TI  - Major Survey Findings of Listening to Mothers(SM) III: New Mothers Speak Out:
      Report of National Surveys of Women's Childbearing ExperiencesConducted October
      December 2012 and January-April 2013.
AB  - To understand the experiences and views of childbearing women in the United
      States and trends over time, Childbirth Connection carried out the third national
      Listening to Mothers survey among 2,400 women who gave birth in U.S. hospitals to
      a single baby from mid-2011 to mid-2012 and could participate in English. A
      follow-up survey directed to the same participants explored postpartum
      experiences, in depth and well into the second year after birth; views about
      maternity care; and some additional pregnancy and birth items. Harris Interactive
      conducted the surveys using a validated methodology that includes data weighting
      to ensure that results closely reflect the target population. The follow-up
      survey was reported in Listening to Mothers III: New Mothers Speak Out. 

PMID- 24453465
TI  - Influence of culture and community perceptions on birth and perinatal care of
      immigrant women: doulas' perspective.
AB  - A qualitative study examined the perceptions of doulas practicing in Washington
      State regarding the influence of cultural and community beliefs on immigrant
      women's birth and perinatal care, as well as their own cultural beliefs and
      values that may affect their ability to work interculturally. The findings
      suggest that doulas can greatly aid immigrant mothers in gaining access to
      effective care by acting as advocates, cultural brokers, and emotional and social
      support. Also, doulas share a consistent set of professional values, including
      empowerment, informed choice, cultural relativism, and scientific/evidence-based
      practice, but do not always recognize these values as culturally based. More
      emphasis on cultural self-awareness in doula training, expanding community doula
      programs, and more integration of doula services in health-care settings are
      recommended. 

PMID- 24453466
TI  - A descriptive survey of the educational preparation and practices of antenatal
      educators in ireland.
AB  - Antenatal education is recommended to prospective parents, yet little is known
      about the educational preparation of the facilitators of this education, or of
      the educational practices they use. The aim of this study was to investigate the
      educational preparation and practices of antenatal educators in Ireland. Data
      were collected using a questionnaire structured on the three components
      (abilities, opportunities, and means) of Stamler's theoretical framework of
      enablement. Eighty-four of the 120 antenatal educators responded (70%), and this
      included midwives, public health nurses, physiotherapists, and private antenatal
      educators. Findings describe a picture of varied educational preparation for the
      antenatal educator with a range of educational practices being used. Within
      public antenatal classes, large class size was a barrier to providing a
      participatory educational approach. 

PMID- 24453467
TI  - More than clinical waste? Placenta rituals among Australian home-birthing women.
AB  - The discursive construction of the human placenta varies greatly between hospital
      and home-birthing contexts. The former, driven by medicolegal discourse, defines
      the placenta as clinical waste. Within this framework, the placenta is as much of
      an afterthought as it is considered the "afterbirth." In home-birth practices,
      the placenta is constructed as a "special" and meaningful element of the
      childbirth experience. I demonstrate this using 51 in-depth interviews with women
      who were pregnant and planning home births in Australia or had recently had home
      births in Australia. Analysis of these interviews indicates that the discursive
      shift taking place in home-birth practices from the medicalized model translates
      into a richer understanding and appreciation of the placenta as a spiritual
      component of the childbirth experience. The practices discussed in this article
      include the burial of the placenta beneath a specifically chosen plant, consuming
      the placenta, and having a lotus birth, which refers to not cutting the umbilical
      cord after the birth of the child but allowing it to dry naturally and break of
      its own accord. By shifting focus away from the medicalized frames of reference
      in relation to the third stage of labor, the home-birthing women in this study
      have used the placenta in various rituals and ceremonies to spiritualize an
      aspect of birth that is usually overlooked. 

PMID- 24453468
TI  - Diet and pregnancy: health-care providers and patient behaviors.
AB  - In this study, associations between health-care providers (HCPs) discussing diet
      with their pregnant patients and patient dietary behavior were assessed in
      addition to factors related to HCPs discussing diet with their patients.
      Questionnaires were completed by 237 pregnant women and 31 HCPs at 12 obstetrics
      gynecology clinics across the United States. Patients provided versus those not
      provided dietary counseling by their HCP were more likely (OR = 2.17, 95%; CI =
      0.75-6.25) to engage in healthy dietary practices. HCPs that discussed multiple
      health behaviors were nearly four times more likely to discuss diet with their
      pregnant patients compared with HCP who did not discuss other health behaviors
      (OR = 3.67, 95%; CI = 1.10-12.28). This study indicates that HCP education can
      positively impact dietary behaviors of their pregnant patients. 

PMID- 24453469
TI  - Effect of highly active antiretroviral therapy (HAART) and menopause on risk of
      progression of cervical dysplasia in human immune-deficiency virus- (HIV-)
      infected women.
AB  - BACKGROUND: More HIV-infected women are reaching older age and menopause, but
      there is limited information on cervical squamous intraepithelial lesions (SILs)
      on these women. METHODS: To assess the effect of HAART and menopause on SILs in
      HIV-infected women, we reviewed the results of Papanicolaou (Pap) tests obtained
      between 1991 and 2011 on 245 women. Progression to SILs was determined by
      comparing Pap test results. The association of HAART and transition to menopause
      on SILs was assessed using survival analysis. RESULTS: Women receiving HAART had
      a 52% reduced risk in the progression to SILs compared to women receiving any
      other antiretroviral regimen or no regimen (CI: 0.33-0.70, P = 0.0001). A greater
      increase of CD4(+) cell counts was associated with a greater reduction on the
      risk of progression to SILs. Menopausal women had a 70% higher risk of
      progression to SILs than premenopausal women (CI: 1.11-2.62, P < 0.0001),
      adjusting for HIV medications, CD4(+) count, duration of HIV infection,
      moderation effect of menopause by age, prior IV drug use, and smoking.
      CONCLUSION: HAART had a positive long-term effect on the progression to SILs.
      However, being younger and menopausal increases the risk of progression.

PMID- 24453470
TI  - Young Adult Outcomes Associated with Teen Pregnancy Among High-Risk Girls in an
      RCT of Multidimensional Treatment Foster Care.
AB  - Teen pregnancy is associated with a host of deleterious outcomes for girls such
      as drug use and poor parenting. Thus, reducing teen pregnancy rates could improve
      long-term developmental outcomes for girls, improving adjustment during young
      adulthood. Based on the positive effects of Multidimensional Treatment Foster
      Care (MTFC) relative to group care (GC) in a study of adolescent girls
      significantly fewer pregnancies reported in the 2-year follow-up for MTFC girls
      the present study followed this sample into young adulthood (approximately 7
      years postbaseline) to examine the effects of adolescent pregnancy on young adult
      substance use and pregnancy-related outcomes. All participants were randomly
      assigned to MTFC (n = 81) or GC (n = 85) as adolescents as part of two RCTs.
      Results from logistic regression analyses indicated that becoming pregnant during
      the 2-year follow-up was significantly related to illicit drug use, miscarriage
      from a new pregnancy, and child welfare involvement at 7 years postbaseline. In
      addition, baseline marijuana use predicted marijuana use at 7 years postbaseline.

PMID- 24453471
TI  - Pitch contour stylization using an optimal piecewise polynomial approximation.
AB  - We propose a dynamic programming (DP) based piecewise polynomial approximation of
      discrete data such that the L2 norm of the approximation error is minimized. We
      apply this technique for the stylization of speech pitch contour. Objective
      evaluation verifies that the DP based technique indeed yields minimum mean square
      error (MSE) compared to other approximation methods. Subjective evaluation
      reveals that the quality of the synthesized speech using stylized pitch contour
      obtained by the DP method is almost identical to that of the original speech.

PMID- 24453472
TI  - Evaluation of Potential Exposure to Metals in Laundered Shop Towels.
AB  - We reported in 2003 that exposure to metals on laundered shop towels (LSTs) could
      exceed toxicity criteria. New data from LSTs used by workers in North America
      document the continued presence of metals in freshly laundered towels. We
      assessed potential exposure to metals based on concentrations of metals on the
      LSTs, estimates of LST usage by employees, and the transfer of metals from LST-to
      hand, hand-to-mouth, and LST-to-lip, under average- or high-exposure scenarios.
      Exposure estimates were compared to toxicity criteria. Under an average-exposure
      scenario (excluding metals' data outliers), exceedances of the California
      Environmental Protection Agency, U.S. Environmental Protection Agency, and the
      Agency for Toxic Substances and Disease Registry toxicity criteria may occur for
      aluminum, cadmium, cobalt, copper, iron, and lead. Calculated intakes for these
      metals were up to more than 400-fold higher (lead) than their respective toxicity
      criterion. For the high-exposure scenario, additional exceedances may occur, and
      high-exposure intakes were up to 1,170-fold higher (lead) than their respective
      toxicity criterion. A sensitivity analysis indicated that alternate plausible
      assumptions could increase or decrease the magnitude of exceedances, but were
      unlikely to eliminate certain exceedances, particularly for lead.

PMID- 24453473
TI  - Association between genotype and phenotype in families with mutations in the
      ABCA4 gene.
AB  - PURPOSE: To investigate the genotype and phenotype in families with adenosine
      triphosphate-binding cassette, sub-family A, member 4 (ABCA4)-associated retinal
      degeneration. METHODS: Three families with at least one family member with known
      homozygous or compound heterozygote mutations in the ABCA4 gene were studied. The
      investigations included full field electroretinography (ff-ERG), multifocal ERG
      (mERG), Goldmann visual fields, optical coherence tomography (OCT), and standard
      ophthalmological examination. Microarray (Asper) was used for ABCA4 genotyping.
      RESULTS: In family 1, the proband (age 23) was homozygote for the c768 G>T
      mutation. She was diagnosed with cone rod dystrophy (CRD) while her aunt (age 69)
      was compound heterozygote for the c768 G>T and c2894 A>G mutations and had
      autosomal recessive retinitis pigmentosa (arRP). The father (age 61) and the
      mother (age 60) of the proband were asymptomatic carriers of the c768 G>T
      mutation. In family 2, the proband (age 25) was homozygote for the c5917del. She
      was diagnosed with CRD. Her father and two sisters were compound heterozygote for
      the c5917del and c5882 G>A mutations. The eldest sister (age 23) suffered from
      Stargardt disease (STGD) while the youngest sister (age 12) and their father (age
      48) had no visual complaints. Anyhow, their ERG measurements indicated changes
      corresponding to STGD. The mother (age 42), (heterozygote for the c5917 delG
      mutation) and the youngest child (age 9; heterozygote for the c5882 G>A mutation)
      had a normal phenotype. In family 3, the proband (age 43) was compound
      heterozygote for c768 G>T and c3113 C>T and had been diagnosed with STGD. Her son
      (age 12), who was homozygote for the c768 G>T mutation, had wider scotomas with
      earlier onset (age 6), ff-ERG cone responses in the lower range of normality, and
      reduced mERG. At the moment, he is classified as having STGD but may progress to
      CRD. The father (age 45) was asymptomatic and heterozygote for the c768 G>T
      mutation. The patients with progressive disorders (CRD or arRP) had prolonged
      implicit times for the 30 Hz flicker ff-ERG and the mERG. All patients with two
      mutations in the ABCA4 gene demonstrated attenuation of retinal thickness on the
      OCT macular map. CONCLUSIONS: This study confirms that ABCA4 mutations lead to a
      spectrum of retinal degenerations ranging from STGD to CRD or arRP. At the time
      of diagnosis, it is not possible to predict the severity of the condition only
      from genotyping. Our results suggest that prolongation of implicit times for the
      ff-ERG and/or mERG seem to be associated with progressive conditions such as CRD
      and arRP. Since ABCA4 mutations are common in the general population, different
      family members can harbor various combinations of mutations resulting in diverse
      phenotype and prognosis in the same family, further emphasizing the importance of
      a combination of genetic and electrophysiological tests at the first visit and
      follow-up.

PMID- 24453474
TI  - CFH haplotypes and ARMS2, C2, C3, and CFB alleles show association with
      susceptibility to age-related macular degeneration in Mexicans.
AB  - PURPOSE: To evaluate the contribution of genetic variants of complement factor H
      (CFH), complement component 2 and 3 (C2 and C3), complement factor B (CFB), and
      age-related maculopathy susceptibility 2 (ARMS2) to age-related macular
      degeneration (AMD) risk in the Mexican Mestizo population. METHODS: Analysis
      included 282 unrelated Mexican patients with advanced AMD, 205 healthy controls,
      and 280 population controls. Stereoscopic fundus images were graded on the
      Clinical Age-Related Maculopathy System (CARMS). We designed a resequencing
      strategy using primers with M13 adaptor for the 23 exons of the CFH gene in a
      subgroup of 96 individuals clinically evaluated: 48 AMD cases and 48 age- and sex
      matched healthy controls. Single nucleotide polymorphisms (SNPs) in C3 (Arg80Gly
      and Pro292Leu), C2 (rs547154), CFB (Leu9His), and ARMS2 (Ala69Ser) were genotyped
      in all patients, healthy and population controls using TaqMan assay. RESULTS: All
      evaluated individuals were Mexican Mestizos, and their genetic ancestry was
      validated using 224 ancestry informative markers and calculating F(st) values.
      The CFH resequencing revealed 19 SNPs and a common variant in the intron 2 splice
      acceptor site; three CFH haplotypes inferred from individual genotypes, showed
      significant differences between cases and controls. The risk alleles in C3
      (rs1047286, odds ratio [OR]=2.48, 95% confidence interval [CI]=1.64-3.75, p=1.59E
      05; rs2230199, OR=2.15, 95% CI=1.48-3.13, p=6.28E-05) and in ARMS2 (rs10490924,
      OR=3.09, 95% CI=2.48-3.86, p=5.42E-23) were strongly associated with risk of AMD.
      The protective effect of alleles in C2 (rs547154) and CFB (rs4151667) showed a
      trend but was not significantly associated after correction for multiple testing.
      CONCLUSIONS: Our results show that ARMS2 and C3 are major contributors to
      advanced AMD in Mexican patients, while the contributions of CFH, C2, and CFB are
      minor to those of other populations, reveling significant ethnic differences in
      minor allele frequencies. We provide evidence that two specific common haplotypes
      in the CFH gene predispose individuals to AMD, while another may confer reduced
      risk of disease in this admixed population.

PMID- 24453475
TI  - Identification of proteins that interact with alpha A-crystallin using a human
      proteome microarray.
AB  - PURPOSE: To identify proteins interacting with alpha A-crystallin (CRYAA) and to
      investigate the potential role that these protein interactions play in the
      function of CRYAA using a human proteome (HuProt) microarray. METHODS: The active
      full-length CRYAA protein corresponding to amino acids 1-173 of CRYAA was
      recombined. A HuProt microarray composed of 17,225 human full-length proteins
      with N-terminal glutathione S-transferase (GST) tags was used to identify protein
      protein interactions. The probes were considered detectable when the signal to
      noise ratio (SNR) was over 1.2. The identified proteins were subjected to
      subsequent bioinformatics analysis using the DAVID database. RESULTS: The HuProt
      microarray results showed that the signals of 343 proteins were higher in the
      recombinant CRYAA group than in the control group. The SNR of 127 proteins was >=
      1.2. The SNR of the following eight proteins was > 3.0: hematopoietic cell
      specific Lyn substrate 1 (HCLS1), Kelch domain-containing 6 (KLHDC6), sarcoglycan
      delta (SGCD), KIAA1706 protein (KIAA1706), RNA guanylyltransferase and 5'
      phosphatase (RNGTT), chromosome 10 open reading frame 57 (C10orf57), chromosome 9
      open reading frame 52 (C9orf52), and plasminogen activator, urokinase receptor
      (PLAUR). The bioinformatics analysis revealed 127 proteins associated with
      phosphoproteins, alternative splicing, acetylation, DNA binding, the nuclear
      lumen, ribonucleotide binding, the cell cycle, WD40 repeats, protein transport,
      transcription factor activity, GTP binding, and cellular response to stress.
      Functional annotation clustering showed that they belong to cell cycle, organelle
      or nuclear lumen, protein transport, and DNA binding and repair clusters. CRYAA
      interacted with these proteins to maintain their solubility and decrease the
      accumulation of denatured target proteins. The protein-protein interactions may
      help CRYAA carry out multifaceted functions. CONCLUSIONS: One-hundred and twenty
      seven of 17,225 human full-length proteins were identified that interact with
      CRYAA. The advent of microarray analysis enables a better understanding of the
      functions of CRYAA as a molecular chaperone.

PMID- 24453477
TI  - Anterior segment optical coherence tomography for demonstrating posterior
      capsular rent in posterior polar cataract.
AB  - AIMS/PURPOSE: To report the preoperative use of anterior segment optical
      coherence tomography (AS-OCT) for the determination of pre-existing posterior
      capsule defect in patients with posterior polar cataract. METHODS: Three patients
      presented with posterior polar cataract and were evaluated preoperatively using
      AS-OCT, revealing in one patient intact posterior capsule and in the other two a
      pre-existing posterior capsule defect not detectable by slit-lamp evaluation. All
      patients underwent phacoemulsification and intraocular lens implantation.
      RESULTS: Intraoperatively, AS-OCT findings were confirmed after cataract surgery
      in all patients. No intra- or late postoperative complications were noted.
      CONCLUSION: AS-OCT could be an additional useful imaging modality in these
      patients, essential for surgical planning and patient consultation.

PMID- 24453476
TI  - Electrophysiological examination in uveitis: a review of the literature.
AB  - PURPOSE: Uveitis is the inflammation of the uveal tract, which usually also
      affects the retina and vitreous humor. The electrophysiological examination is an
      objective ocular examination that includes the electroretinogram, visual evoked
      potentials, the electrooculogram, the multifocal electroretinogram, and
      multifocal visual evoked potentials. Our aim is to review the literature of the
      use of the electrophysiological examination in cases of uveitis. METHODS: We
      performed a systematic search of the literature of published papers until October
      2012 using the PubMed search engine. The key terms that were used were "uveitis",
      "electrophysiological examination", "electroretinogram", "visual evoked
      potentials", "electrooculogram", "multifocal electroretinogram", and "multifocal
      visual evoked potentials" in multiple combinations. To the best of our knowledge,
      this is the first review concerning the assessment of electrophysiology in
      uveitis. RESULTS: Our search of the literature demonstrated that the
      electrophysiological examination, mainly by means of electroretinogram,
      multifocal electroretinogram, and visual evoked potentials, is performed in
      several cases of uveitis for many purposes, including diagnosis and monitoring of
      disease progression and treatment efficacy. The electrophysiological examination
      is more useful in patients with multiple evanescent white dot syndrome, acute
      posterior multifocal placoid pigment epitheliopathy, birdshot chorioretinopathy,
      Vogt-Koyanagi-Harada disease, Adamantiades-Behcet disease, ocular syphilis, and
      Fuchs heterochromic cyclitis. CONCLUSION: This review summarizes the use of the
      electrophysiological examination in uveitic patients and underlines its value as
      a useful tool in the objective assessment and the monitoring of the disease.

PMID- 24453478
TI  - Innate immunity interactome dynamics.
AB  - Innate immune response involves protein-protein interactions, deoxyribonucleic
      acid (DNA)-protein interactions and signaling cascades. So far, thousands of
      protein-protein interactions have been curated as a static interaction map.
      However, protein-protein interactions involved in innate immune response are
      dynamic. We recorded the dynamics in the interactome during innate immune
      response by combining gene expression data of lipopolysaccharide (LPS)-stimulated
      dendritic cells with protein-protein interactions data. We identified the
      differences in interactome during innate immune response by constructing
      differential networks and identifying protein modules, which were up-/down
      regulated at each stage during the innate immune response. For each protein
      complex, we identified enriched biological processes and pathways. In addition,
      we identified core interactions that are conserved throughout the innate immune
      response and their enriched gene ontology terms and pathways. We defined two
      novel measures to assess the differences between network maps at different time
      points. We found that the protein interaction network at 1 hour after LPS
      stimulation has the highest interactions protein ratio, which indicates a role
      for proteins with large number of interactions in innate immune response. A
      pairwise differential matrix allows for the global visualization of the
      differences between different networks. We investigated the toll-like receptor
      subnetwork and found that S100A8 is down-regulated in dendritic cells after LPS
      stimulation. Identified protein complexes have a crucial role not only in innate
      immunity, but also in circadian rhythms, pathways involved in cancer, and p53
      pathways. The study confirmed previous work that reported a strong correlation
      between cancer and immunity. 

PMID- 24453479
TI  - Patient perspectives on the impact of acromegaly: results from individual and
      group interviews.
AB  - PURPOSE: Acromegaly is a chronic condition resulting from a growth hormone
      secreting pituitary tumor that can substantially impact patients' physical and
      emotional well-being. We sought to understand the impact of acromegaly on disease
      related concerns and treatment choices from the patient perspective. The path to
      diagnosis, current disease management, interactions with the treating health care
      providers (HCPs), and support networks were also assessed. METHODS: Acromegaly
      patients were recruited primarily from a patient support group (Acromegaly
      Community). In Phase I, ten patients participated over the course of 5 days in a
      moderated online discussion board and they answered questions about their
      disease. In Phase II, a separate nine-patient cohort participated in face-to-face
      interviews conducted during an acromegaly patient conference. Data were
      summarized qualitatively by grouping similar answers and quotations. RESULTS:
      Nineteen acromegaly patients were recruited across the two cohorts, and both
      groups shared similar concerns. They demonstrated a notable interest in
      understanding their disease and its treatment. Patients were focused on the
      impact of the disease on their life, and they expressed a desire to get beyond
      reminders of their disease. The patients described long journeys to a correct
      diagnosis and relief at having a name for their condition. Many shared a sense of
      shock at needing pituitary surgery and felt unsatisfied by the treatment decision
      process, motivating them to discuss it with other patients. Patients not
      connected to a patient support group reported feeling helpless and lonely. Most
      patients shared a desire to improve their general knowledge about acromegaly to
      spare others their protracted diagnostic period. Patients also reported hesitancy
      in asking questions or sharing details about the disease's impact on their lives
      with their HCPs. CONCLUSION: Acromegaly can be a life-changing diagnosis with
      profound, ongoing effects on patients' lives. Patients struggle with many issues
      they fail to openly share with their HCPs, but may discuss these issues more
      easily with other acromegaly patients. Better collaboration between patients and
      care providers could lead to increased patient satisfaction.

PMID- 24453480
TI  - GeneSV - an Approach to Help Characterize Possible Variations in Genomic and
      Protein Sequences.
AB  - A computational approach for identification and assessment of genomic sequence
      variability (GeneSV) is described. For a given nucleotide sequence, GeneSV
      collects information about the permissible nucleotide variability (changes that
      potentially preserve function) observed in corresponding regions in genomic
      sequences, and combines it with conservation/variability results from protein
      sequence and structure-based analyses of evaluated protein coding regions. GeneSV
      was used to predict effects (functional vs. non-functional) of 37 amino acid
      substitutions on the NS5 polymerase (RdRp) of dengue virus type 2 (DENV-2), 36 of
      which are not observed in any publicly available DENV-2 sequence. 32 novel
      mutants with single amino acid substitutions in the RdRp were generated using a
      DENV-2 reverse genetics system. In 81% (26 of 32) of predictions tested, GeneSV
      correctly predicted viability of introduced mutations. In 4 of 5 (80%) mutants
      with double amino acid substitutions proximal in structure to one another GeneSV
      was also correct in its predictions. Predictive capabilities of the developed
      system were illustrated on dengue RNA virus, but described in the manuscript a
      general approach to characterize real or theoretically possible variations in
      genomic and protein sequences can be applied to any organism. 

PMID- 24453481
TI  - Relationship between cognitive impairment and nutritional assessment on
      functional status in Calabrian long-term-care.
AB  - OBJECTIVE: The interaction between dementia and nutritional state is very complex
      and not yet fully understood. The aim of the present study was to assess the
      interaction between cognitive impairment and nutritional state in a cohort of
      residential elderly in relationship with functional condition of patients and
      their load of assistance in long-term-care facilities of the National Association
      of Third Age Structures (ANASTE) Calabria. METHODS: One hundred seventy-four
      subjects (122 female and 52 male) were admitted to the long-term-care ANASTE
      Calabria study. All patients underwent multidimensional geriatric assessment.
      Nutritional state was assessed with the Mini Nutritional Assessment (MNA),
      whereas cognitive performance was evaluated by the Mini-Mental State Examination
      (MMSE). The functional state was assessed by Barthel Index (BI) and Activity
      Daily Living (ADL). The following nutritional biochemical parameters were also
      evaluated: albumin, cholesterol, iron, and hemoglobin. All patients were
      reassessed 180 days later. RESULTS: A severe cognitive impairment in MMSE
      performance was displayed in 49.7% patients, while 39.8% showed a moderate
      deficit; 6.9% had a slight deficit; and 3.4% evidenced no cognitive impairment.
      In MNA, 30% of patients exhibited an impairment of nutritional state; 56% were at
      risk of malnutrition; and 14% showed no nutritional problems. Malnutrition was
      present in 42% of patients with severe cognitive impairment, but only 4% of
      malnourished patients showed moderate cognitive deficit. The statistical analysis
      displayed a significant correlation between MNA and MMSE (P<0.001), as did MMSE
      correlated with Activity Daily Living (P<0.001) and BI (P<0.05). MNA correlated
      with BI (P<0.001) and albumin (P<0.001). The follow-up showed a strong
      correlation between cognitive deterioration and worsening of nutritional state
      (P<0.005) as well as with the functional state (P<0.05) and mortality (P<0.01).
      CONCLUSION: The present study clearly shows that malnutrition may play an
      important role in the progression of cognitive loss.

PMID- 24453483
TI  - The effectiveness of a combined exercise intervention on physical fitness factors
      related to falls in community-dwelling older adults.
AB  - This study aimed to evaluate the effectiveness of an innovative exercise program
      on muscle strength, balance, and gait kinematics in elderly community-dwellers.
      The exercise program included strength and balance training and the 8-form Tai
      Chi Chuan. The measurements were carried out at baseline and 12 weeks, and
      consisted of four physical performance tests, joint isokinetic strength tests,
      and three-dimensional gait analysis. Fifty-six community-dwelling older adults
      aged 60-80 years old were randomly assigned to an intervention or control group.
      After 12 weeks, the intervention group showed a 17.6% improvement in the timed up
      and go test, accompanied by a 54.7% increase in the 30-second chair stand test
      score. Significant increases in the score of star excursion balance tests, and
      the strength of the extensor and flexor muscles at knee and ankle joints were
      also observed. In addition, the intervention group walked at a faster speed with
      a longer step length, shorter support phase, and a greater sagittal plane range
      of motion at the hip and ankle joints. No statistical improvements were seen in
      the control group. This study provided an effective, evidence-based falls
      prevention program that can be implemented in community settings to improve
      physical fitness and reduce fall risks among community-dwelling older adults. The
      star excursion balance test could be a sensitive measure of physical performance
      for fall risk assessment in older people. 

PMID- 24453484
TI  - Visual outcome of intravitreal ranibizumab for exudative age-related macular
      degeneration: timing and prognosis.
AB  - PURPOSE: To describe 1-year clinical results of intravitreal ranibizumab
      treatment in patients with choroidal neovascularization secondary to exudative
      age-related macular degeneration (AMD) and to evaluate whether early treatment is
      a predictive value for prognosis of the disease. MATERIALS AND METHODS: Clinical
      records were retrospectively reviewed of 104 eyes that underwent intravitreal
      ranibizumab therapy for exudative AMD. Patients were divided into two groups
      according to their symptom duration: group 1, <1 month; and group 2, 1-3 months.
      After three monthly injections, patients were examined monthly, and subsequent
      injections were performed as needed. RESULTS: There were 43 female (48.9%) and 45
      males (51.1%). The follow-up time was 13.7+/-1.9 (12-19) months. The mean
      logarithm of minimum angle of resolution best-corrected visual acuity (BCVA)
      improved significantly, from 0.45+/-0.639 at baseline to 0.08+/-0.267 at 12
      months in group 1, and from 1.06+/-0.687 at baseline to 0.75+/-0.563 at 12 months
      in group 2. The increase in BCVA was statistically significant in group 1
      (P=0.009). The mean central retinal thickness (CRT) decreased significantly, from
      355.13+/-119.93 MUm at baseline to 250.85+/-45.48 MUm at 12 months in group 1,
      and from 371.88+/-91.047 MUm at baseline to 268.61+/-53.51 MUm at 12 months in
      group 2. The decrease in CRT was statistically significant in group 1 (P=0.001).
      CONCLUSION: Intravitreal ranibizumab therapy was effective in significantly
      increasing mean BVCA and reducing CRT. Shorter duration of AMD, as measured by
      the subjective duration of visual symptoms, is associated with better visual
      outcome after treatment.

PMID- 24453485
TI  - Selection of acupoints for managing upper-extremity spasticity in chronic stroke
      patients.
AB  - BACKGROUND: This study investigated the clinical efficacy of electroacupuncture
      (EA) in inhibiting upper-extremity spasticity in chronic stroke patients, and
      also in mapping a unique preliminary acupoint-selection protocol. METHODS:
      Fifteen patients were divided into two groups: patients in the control group
      (n=6) received minimal acupuncture (MA), and those in the experimental group
      (n=9) received EA. Four acupoints, which include Neiguan (PC6), Shaohai (HT3),
      Zeqian (Ex-UE, A32), and Shounizhu (EX-UE), were treated near the motor points of
      the muscles for elbow flexion, forearm pronation, and finger flexion. Both groups
      were treated for twelve sessions, 20 minutes per session, for 6 weeks (two
      sessions per week). The outcome measures in this study included angle of muscle
      reaction (R1), passive range of motion (R2), and dynamic component (R2-R1).
      RESULTS: In the experimental group, the R2-R1 of the elbow joint was
      significantly decreased at 1 (P=0.0079), 3 (P=0.0013), and 6 weeks (P=0.0149)
      after treatment compared with pretreatment levels (P<0.05). The between-group
      difference in the R2-R1 of the elbow joint after the 6-week treatment was
      statistically significant. CONCLUSION: Combining the 6-week EA and standard
      rehabilitation treatment reduced the spasticity of the elbow for chronic stroke
      survivors. However, no significant effect was observed in the spasticity of the
      wrist joints. The choice of acupoints and the frequency of EA have to be taken
      into account to achieve a positive treatment effect. The correlation between
      acupoints and motor points provides a model of acupoint selection to improve
      spasticity.

PMID- 24453486
TI  - Novel kojic acid-polymer-based magnetic nanocomposites for medical applications.
AB  - Iron oxide magnetic nanoparticles (MNPs) were synthesized by the coprecipitation
      of iron salts in sodium hydroxide followed by coating separately with chitosan
      (CS) and polyethylene glycol (PEG) to form CS-MNPs and PEG-MNPs nanoparticles,
      respectively. They were then loaded with kojic acid (KA), a pharmacologically
      bioactive natural compound, to form KA-CS-MNPs and KA-PEG-MNPs nanocomposites,
      respectively. The MNPs and their nanocomposites were characterized using powder X
      ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric
      analysis, vibrating sample magnetometry, and scanning electron microscopy. The
      powder X-ray diffraction data suggest that all formulations consisted of highly
      crystalline, pure magnetite Fe3O4. The Fourier transform infrared spectroscopy
      and thermogravimetric analysis confirmed the presence of both polymers and KA in
      the nanocomposites. Magnetization curves showed that both nanocomposites (KA-CS
      MNPs and KA-PEG-MNPs) were superparamagnetic with saturation magnetizations of
      8.1 emu/g and 26.4 emu/g, respectively. The KA drug loading was estimated using
      ultraviolet-visible spectroscopy, which gave a loading of 12.2% and 8.3% for the
      KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The release profile of
      the KA from the nanocomposites followed a pseudo second-order kinetic model. The
      agar diffusion test was performed to evaluate the antimicrobial activity for both
      KA-CS-MNPs and KA-PEG-MNPs nanocomposites against a number of microorganisms
      using two Gram-positive (methicillin-resistant Staphylococcus aureus and Bacillus
      subtilis) and one Gram-negative (Salmonella enterica) species, and showed some
      antibacterial activity, which could be enhanced in future studies by optimizing
      drug loading. This study provided evidence for the promise for the further
      investigation of the possible beneficial biological activities of KA and both KA
      CS-MNPs and KA-PEG-MNPs nanocomposites in nanopharmaceutical applications. 

PMID- 24453487
TI  - Ginkgo biloba: a natural reducing agent for the synthesis of cytocompatible
      graphene.
AB  - BACKGROUND: Graphene is a novel two-dimensional planar nanocomposite material
      consisting of rings of carbon atoms with a hexagonal lattice structure. Graphene
      exhibits unique physical, chemical, mechanical, electrical, elasticity, and
      cytocompatible properties that lead to many potential biomedical applications.
      Nevertheless, the water-insoluble property of graphene restricts its application
      in various aspects of biomedical fields. Therefore, the objective of this work
      was to find a novel biological approach for an efficient method to synthesize
      water-soluble and cytocompatible graphene using Ginkgo biloba extract (GbE) as a
      reducing and stabilizing agent. In addition, we investigated the biocompatibility
      effects of graphene in MDA-MB-231 human breast cancer cells. MATERIALS AND
      METHODS: Synthesized graphene oxide (GO) and GbE-reduced GO (Gb-rGO) were
      characterized using various sequences of techniques: ultraviolet-visible (UV-vis)
      spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light
      scattering (DLS), scanning electron microscopy (SEM), atomic force microscopy
      (AFM), and Raman spectroscopy. Biocompatibility of GO and Gb-rGO was assessed in
      human breast cancer cells using a series of assays, including cell viability,
      apoptosis, and alkaline phosphatase (ALP) activity. RESULTS: The successful
      synthesis of graphene was confirmed by UV-vis spectroscopy and FTIR. DLS analysis
      was performed to determine the average size of GO and Gb-rGO. X-ray diffraction
      studies confirmed the crystalline nature of graphene. SEM was used to investigate
      the surface morphologies of GO and Gb-rGO. AFM was employed to investigate the
      morphologies of prepared graphene and the height profile of GO and Gb-rGO. The
      formation of defects in Gb-rGO was confirmed by Raman spectroscopy. The
      biocompatibility of the prepared GO and Gb-rGO was investigated using a water
      soluble tetrazolium 8 assay on human breast cancer cells. GO exhibited a dose
      dependent toxicity, whereas Gb-rGO-treated cells showed significant
      biocompatibility and increased ALP activity compared to GO. CONCLUSION: In this
      work, a nontoxic natural reducing agent of GbE was used to prepare soluble
      graphene. The as-prepared Gb-rGO showed significant biocompatibility with human
      cancer cells. This simple, cost-effective, and green procedure offers an
      alternative route for large-scale production of rGO, and could be used for
      various biomedical applications, such as tissue engineering, drug delivery,
      biosensing, and molecular imaging.

PMID- 24453488
TI  - Short communication: selective cytotoxicity of curcumin on osteosarcoma cells
      compared to healthy osteoblasts.
AB  - Curcumin is a natural phenolic compound extracted from the plant Curcuma longa L.
      In previous studies, curcumin has been shown to have anticancer, antioxidant, and
      anti-inflammatory effects. In this study, the cytotoxicity of different
      concentrations (5, 10, 25, 50, 75, and 100 MUM) of curcumin dissolved in dimethyl
      sulfoxide was compared between MG-63 osteosarcoma and healthy human osteoblast
      cells. Consequently, the viability of osteosarcoma cells was less than 50% at a
      concentration of 10 MUM compared to the control sample without curcumin, but
      healthy osteoblast cells had at least 80% viability throughout all the
      concentrations tested. The results demonstrated that MG-63 osteosarcoma cells
      were much more sensitive in terms of cytotoxicity to curcumin, while the healthy
      human osteoblasts exhibited a higher healthy viability after 24 hours of curcumin
      treatment. Therefore, this study showed that at the right concentrations (5 MUM
      to 25 MUM), curcumin, along with a proper nanoparticle drug delivery carrier, may
      selectively kill bone cancer cells over healthy bone cells. 

PMID- 24453489
TI  - Incorporating and integrating cognitive event-related potentials in the
      management of psychiatric disorders.

PMID- 24453491
TI  - Frequency of tuberculosis among diabetic patients in the People's Republic of
      China.
AB  - The People's Republic of China has nearly the highest incidence of both diabetes
      mellitus (DM) and tuberculosis (TB) worldwide. DM increases the risk of TB by two
      to three times and adversely affects TB treatment outcomes. The increasing
      epidemic of DM in the People's Republic of China is due to decreased physical
      activity, unhealthy diet, and obesity. Over the last 20 years, the excellent free
      China National Tuberculosis Program has been set up, and the "DOTS" (directly
      observed treatment + short-course chemotherapy) model for TB control has
      successfully reduced the burden of TB, but the disease is still a considerable
      problem. Given the high burden of TB and DM in the People's Republic of China and
      the relationship between the two diseases, it is sensible to screen DM patients
      for TB. A bidirectional screening of the two diseases was conducted in the
      People's Republic of China from 2011 to 2012, which identified a TB incidence in
      patients with DM of about 958 per 100,000. Here, we report the findings of our
      recent study on the incidence of TB among diabetic patients in the People's
      Republic of China. The data agree with those of previous reports. 

PMID- 24453490
TI  - Effectiveness and safety of Nintendo Wii Fit PlusTM training in children with
      migraine without aura: a preliminary study.
AB  - BACKGROUND: Migraine without aura (MoA) is a painful syndrome, particularly in
      childhood; it is often accompanied by severe impairments, including emotional
      dysfunction, absenteeism from school, and poor academic performance, as well as
      issues relating to poor cognitive function, sleep habits, and motor coordination.
      MATERIALS AND METHODS: The study population consisted of 71 patients affected by
      MoA (32 females, 39 males) (mean age: 9.13+/-1.94 years); the control group
      consisted of 93 normally developing children (44 females, 49 males) (mean age:
      8.97+/-2.03 years) recruited in the Campania school region. The entire population
      underwent a clinical evaluation to assess total intelligence quotient level,
      visual-motor integration (VMI) skills, and motor coordination performance, the
      later using the Movement Assessment Battery for Children (M-ABC). Children
      underwent training using the Wii-balance board and Nintendo Wii Fit PlusTM
      software (Nintendo Co, Ltd, Kyoto, Japan); training lasted for 12 weeks and
      consisted of three 30-minute sessions per week at their home. RESULTS: The two
      starting populations (MoA and controls) were not significantly different for age
      (P=0.899) and sex (P=0.611). M-ABC and VMI performances at baseline (T0) were
      significantly different in dexterity, balance, and total score for M-ABC
      (P<0.001) and visual (P=0.003) and motor (P<0.001) tasks for VMI. After 3 months
      of Wii training (T1), MoA children showed a significant improvement in M-ABC
      global performance (P<0.001), M-ABC dexterity (P<0.001), M-ABC balance (P<0.001),
      and VMI motor task (P<0.001). CONCLUSION: Our study reported the positive effects
      of the Nintendo Wii Fit PlusTM system as a rehabilitative device for the
      visuomotor and balance skills impairments among children affected by MoA, even if
      further research and longer follow-up are needed.

PMID- 24453492
TI  - Prevalence of cannabis residues in psychiatric patients: a case study of two
      mental health referral hospitals in Uganda.
AB  - Various studies have reported that abuse of cannabis is a risk factor for
      psychosis. The aims of this study were to determine the prevalence of delta 9
      tetrahydrocanabinol (Delta(9)-THC), a major metabolite of cannabis, in
      psychiatric patients in Uganda, and to assess the diagnostic capacity of two
      referral mental health hospitals to screen patients for exposure to cannabis in
      Uganda. Socio-demographic characteristics of the patients were collected through
      questionnaires and review of medical records. Urine samples were collected from
      100 patients and analyzed using Delta(9)-THC immunochromatographic kit (Standard
      Diagnostics((r)), South Korea). Seventeen percent of the patients tested positive
      for Delta(9)-THC residues in their urine. There was strong association (P < 0.05)
      between history of previous abuse of cannabis and presence of Delta(9)-THC
      residues in the urine. Alcohol, cocaine, heroin, pethidine, tobacco, khat and
      kuber were the other substances abused in various combinations. Both referral
      hospitals lacked laboratory diagnostic kits for detection of cannabis in
      psychiatric patients. In conclusion, previous abuse of cannabis is associated
      with occurrence of the residues in psychiatric patients, yet referral mental
      health facilities in Uganda do not have the appropriate diagnostic kits for
      detection of cannabis residues as a basis for evidence-based psychotherapy. 

PMID- 24453493
TI  - Oncotype dx results in multiple primary breast cancers.
AB  - PURPOSE: To determine whether multiple primary breast cancers have similar
      genetic profiles, specifically Oncotype Dx Recurrence Scores, and whether
      obtaining Oncotype Dx on each primary breast cancer affects chemotherapy
      recommendations. METHODS: A database of patients with hormone receptor-positive,
      lymph node-negative, breast cancer was created for those tumors that were sent
      for Oncotype Dx testing from the University of Michigan Health System from
      1/24/2005 to 2/25/2013. Retrospective chart review abstracted details of tumor
      location, histopathology, distance between tumors, Oncotype Dx results, and
      chemotherapy recommendations. RESULTS: Six hundred and sixty-six patients for
      whom Oncotype Dx testing was sent were identified, with 22 patients having
      multiple breast tumor specimens sent. Of the 22 patients who had multiple samples
      sent for analysis, chemotherapy recommendations were changed in 6 of 22 patients
      (27%) based on significant differences in Oncotype Dx Recurrence Scores.
      Qualitatively, there seems to be a greater difference in genetic profile in
      tumors appearing simultaneously on different breasts when compared to multiple
      tumors on the same breast. There was no association between distance between
      tumors and difference in Oncotype Dx scores for tumors on the same breast.
      CONCLUSIONS: Oncotype Dx testing on multiple primary breast cancers altered
      management in regards to chemotherapy recommendations and should be considered
      for multiple primary breast cancers.

PMID- 24453494
TI  - Job satisfaction among nurses working in the private and public sectors: a
      qualitative study in tertiary care hospitals in Pakistan.
AB  - BACKGROUND: Many low and middle income countries lack the human resources needed
      to deliver essential health interventions. A health care system with a limited
      number of nurses cannot function effectively. Although the recommended nurse to
      doctor ratio is 4:1, the ratio in Pakistan is reversed, with 2.7 doctors to one
      nurse. METHODS: A qualitative study using narrative analysis was undertaken in
      public and private tertiary care hospitals in Pakistan to examine and compare job
      satisfaction among nurses and understand the factors affecting their work
      climate. Interactive interviews were conducted with nurses working with
      inpatients and outpatients. RESULTS: All of the respondents had joined the
      profession by choice and were supported by their families in their decision to
      pursue their career, but now indicated that they were dissatisfied with their
      jobs. Three types of narratives were identified, namely, "Working in the spirit
      of serving humanity", "Working against all odds", and "Working in a functional
      system and facing pressures of increased accountability". Nurses working in a
      public sector hospital are represented in the first two narrative types, whereas
      the third represents those working in a private sector hospital. The first
      narrative represents nurses who were new in the profession and despite hard
      working conditions were performing their duties. The second narrative represents
      nurses working in the public sector with limited resources, and the third
      narrative is a representation of nurses who were working hard and stressed out
      despite a well functioning system. CONCLUSION: The study shows that the presence
      of a well trained health workforce is vital, and that certain aspects of its
      organization are key, including numbers (available quantity), skill mix (health
      team balance), distribution (urban/rural), and working conditions (compensation,
      nonfinancial incentives, and workplace safety). This study has identified the
      need to reform policies for retaining the nursing workforce. Simple measures
      requiring better management practices could substantially improve the working
      environment and hence retention of nurses.

PMID- 24453495
TI  - Bisphenol A (BPA) Found in Humans and Water in Three Geographic Regions with
      Distinctly Different Levels of Economic Development.
AB  - The suspected endocrine disruptor bisphenol A (BPA) is associated with the
      manufacture, distribution, and use of epoxy resins and polycarbonate plastics;
      thus, studies of this compound have focused primarily on urban areas in developed
      countries. This small study investigating urinary BPA of 109 people was conducted
      in the urban United States, urban Jamaica, and rural Ghana. Additionally, local
      drinking and surface water samples were collected and analyzed from areas near
      study participants. Levels of BPA in both urine and water were comparable among
      all three sites. Thus, future studies of BPA should consider expanding
      investigations to rural areas not typically associated with the compound. 

PMID- 24453497
TI  - Estimation of utility values from visual analog scale measures of health in
      patients undergoing cardiac surgery.
AB  - INTRODUCTION: In health economic evaluations, mapping can be used to estimate
      utility values from other health outcomes in order to calculate quality adjusted
      life-years. Currently, no methods exist to map visual analog scale (VAS) scores
      to utility values. This study aimed to develop and propose a statistical
      algorithm for mapping five dimensions of health, measured on VASs, to utility
      scores in patients suffering from cardiovascular disease. METHODS: Patients
      undergoing coronary artery bypass grafting at Aalborg University Hospital in
      Denmark were asked to score their health using the five VAS items (mobility, self
      care, ability to perform usual activities, pain, and presence of anxiety or
      depression) and the EuroQol 5 Dimensions questionnaire. Regression analysis was
      used to estimate four mapping models from patients' age, sex, and the self
      reported VAS scores. Prediction errors were compared between mapping models and
      on subsets of the observed utility scores. Agreement between predicted and
      observed values was assessed using Bland-Altman plots. RESULTS: Random effects
      generalized least squares (GLS) regression yielded the best results when
      quadratic terms of VAS scores were included. Mapping models fitted using the
      Tobit model and censored least absolute deviation regression did not appear
      superior to GLS regression. The mapping models were able to explain approximately
      63%-65% of the variation in the observed utility scores. The mean absolute error
      of predictions increased as the observed utility values decreased. CONCLUSION: We
      concluded that it was possible to predict utility scores from VAS scores of the
      five dimensions of health used in the EuroQol questionnaires. However, the use of
      the mapping model may be inappropriate in more severe conditions.

PMID- 24453496
TI  - Update on otitis media - prevention and treatment.
AB  - Acute otitis media and otitis media with effusion are common childhood disorders,
      a source of significant morbidity, and a leading cause of antibiotic prescription
      in primary health care. Although effective treatments are available, some
      shortcomings remain, and thus better treatments would be welcome. Recent
      discoveries within the field of otitis media research relating to its etiology
      and pathogenesis have led to further investigation aimed at developing novel
      treatments. This article provides a review of the latest evidence relating to the
      understanding of acute otitis media and otitis media with effusion, current
      treatment strategies, their limitations, new areas of research, and novel
      strategies for treatment. 

PMID- 24453498
TI  - Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of
      rheumatoid arthritis.
AB  - Immune/inflammatory cells act in rheumatoid arthritis (RA)-affected patients by
      synthesizing several inflammatory mediators, including cytokines that initiate
      intracellular signaling. Recently, small molecule inhibitors of transduction and
      transcription signals that influence the intracellular pathways (such as the
      Janus kinase [JAK] family of tyrosine kinases) have been tested for RA treatment.
      Four members of the JAK family are known: JAK1, JAK2, JAK3, and TyK2. JAK1/JAK3
      constitutively binds to the cytoplasmic portion of the cytokine receptor - the
      common gamma chain - that represents a common subunit of several cytokines
      involved in T-cell and natural killer cell development, as well as in B-cell
      activation. Tofacitinib is an oral JAK inhibitor that is now available and
      effective in RA treatment, as shown in multiple Phase II and Phase III clinical
      trials. However, long-term safety data and comparisons with other disease
      modifying antirheumatic drugs and small molecule inhibitors are necessary to
      better determine the role of tofacitinib in RA. 

PMID- 24453499
TI  - Mitochondrial disorder caused Charles Darwin's cyclic vomiting syndrome.
AB  - BACKGROUND: Charles Darwin (CD), "father of modern biology," suffered from
      multisystem illness from early adulthood. The most disabling manifestation was
      cyclic vomiting syndrome (CVS). This study aims at finding the possible cause of
      CVS in CD. METHODS: A literature search using the PubMed database was carried
      out, and CD's complaints, as reported in his personal writings and those of his
      relatives, friends, colleagues, biographers, were compared with various
      manifestations of mitochondrial disorders (MIDs), known to cause CVS, described
      in the literature. RESULTS: Organ tissues involved in CD's disease were brain,
      nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral
      manifestations included episodic headache, visual disturbance, episodic memory
      loss, periodic paralysis, hysterical crying, panic attacks, and episodes of
      depression. Manifestations of polyneuropathy included numbness, paresthesias,
      increased sweating, temperature sensitivity, and arterial hypotension. Muscular
      manifestations included periods of exhaustion, easy fatigability, myalgia, and
      muscle twitching. Cardiac manifestations included episodes of palpitations and
      chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal
      seasickness, eructation, belching, and flatulence. Dermatological manifestations
      included painful lips, dermatitis, eczema, and facial edema. Treatments with
      beneficial effects to his complaints were rest, relaxation, heat, and
      hydrotherapy. CONCLUSION: CVS in CD was most likely due to a multisystem,
      nonsyndromic MID. This diagnosis is based upon the multisystem nature of his
      disease, the fact that CVS is most frequently the manifestation of a MID, the
      family history, the variable phenotypic expression between affected family
      members, the fact that symptoms were triggered by stress, and that only few
      symptoms could not be explained by a MID.

PMID- 24453500
TI  - Pulsed radiofrequency treatment of the lumbar dorsal root ganglion in patients
      with chronic lumbar radicular pain: a randomized, placebo-controlled pilot study.
AB  - BACKGROUND: No proof of efficacy, in the form of a randomized controlled trial
      (RCT), exists to support pulsed radiofrequency (PRF) treatment of the dorsal root
      ganglion (DRG) for chronic lumbar radicular (CLR) pain. We determined the
      feasibility of a larger trial (primary objective), and also explored the efficacy
      of PRF in decreasing pain on a visual analog scale (VAS) and improving the
      Oswestry Disability Index. METHODS: This was a single-center, placebo-controlled,
      triple-blinded RCT. Patients were randomized to a placebo group (needle
      placement) or a treatment group (PRF at 42 degrees C for 120 seconds to the DRG).
      Patients were followed up for 3 months post procedure. Outcomes with regard to
      pain, Oswestry Disability Index score, and side effects were analyzed on an
      intention-to-treat basis. RESULTS: Over 15 months, 350 potential patients were
      identified and 56 were assessed for eligibility. Fifteen of them did not meet the
      selection criteria. Of the 41 eligible patients, 32 (78%) were recruited. One
      patient opted out before intervention. Three patients were lost to follow-up at 3
      months. Mean VAS differences were not significantly different at 4 weeks (-0.36,
      95% confidence interval [CI], -2.29, 1.57) or at 3 months (-0.76, 95% CI, -3.14,
      1.61). The difference in mean Oswestry Disability Index score was also not
      significantly different at 4 weeks (-2%, 95% CI, -14%, 10%) or 3 months (-7%, 95%
      CI, -21%, 6%). There were no major side effects. Six of 16 patients in the PRF
      group and three of 15 in the placebo group showed a >50% decrease in VAS score.
      CONCLUSION: The recruitment rate was partially successful. At 3 months, the
      relative success of PRF-DRG was small. A large-scale trial to establish efficacy
      is not practically feasible considering the small effect size, which would
      necessitate recruitment of a challengingly large number of participants over a
      number of years. Until clear parameters for application of PRF are established,
      clinicians will need to use their individual judgment regarding its clinical
      applicability, given the present evidence.

PMID- 24453501
TI  - Older Adults without Radiographic Knee Osteoarthritis: Knee Alignment and Knee
      Range of Motion.
AB  - This study describes knee alignment and active knee range of motion (ROM) in a
      community-based group of 78-year old adults (n = 143) who did not have
      radiographic evidence of knee osteoarthritis in either knee (KL < 2). Although
      knee malalignment is a risk factor for knee osteoarthritis, most women and men
      had either valgus or varus alignments. Notably, no men were valgus in both knees.
      Women with both knees valgus had significantly greater body mass index (P >
      0.001) than women with varus or straight knees. Men and women with valgus or
      varus knee alignments had generally lower ROM than individuals with both knees
      straight. In summary, this study highlights the complex relationships among knee
      alignment, ROM, body mass index, and gender in elderly adults without
      radiographic knee osteoarthritis. 

PMID- 24453502
TI  - Temporary Endocavitary Pacemakers and their Use and Misuse: the Least is Better.
AB  - Temporary pacemakers are classically indicated for severe bradydysrhythmia,
      especially when the clinical settings require prompt intervention. Implantation
      of a temporary pacemaker is not a benign procedure since it may be associated
      with serious adverse events such as infection, cardiac perforation, and lead
      dislodgment. Accordingly, we recommend, when the clinical condition allows, to
      proceed directly with permanent pacemaker implantation without prior use of a
      temporary pacemaker. However, if a temporary pacemaker is required, it should be
      maintained for the shortest time possible. This policy allows avoiding or
      decreasing the potential complications associated with temporary pacemaker
      implantation. 

PMID- 24453503
TI  - Narcolepsy Associated with Duane's Syndrome.
AB  - The best characterised disorder of REM sleep, narcolepsy has never previously
      been associated with Duane's syndrome, in which there is developmental failure of
      the abducens nerve and its nucleus. The major brain stem nuclei responsible for
      REM sleep generation are situated in the pons in close proximity to the abducens
      nerve nucleus. We report the novel combination of Duane's syndrome and
      narcolepsy, providing new insight into the pathogenesis of narcolepsy. 

PMID- 24453504
TI  - Ascites drainage leading to intestinal adhesions at the mesentery of the small
      intestine with fatal outcome.
AB  - A common problem in patients with chronic liver diseases and liver cirrhosis is
      the development of ascites. First line therapy for ascites is the restriction of
      sodium intake and a diuretic treatment. Paracentesis is indicated in patients
      with large compromising volumes of ascites. In selected cases, permanent drainage
      of ascites over prolonged periods of time may be indicated. In the case presented
      here, a 66-year-old male patient, who was hospitalized with liver cirrhosis
      caused by alcoholic abuse, required permanent drainage of ascites. After three
      weeks of continuous ascites drainage, he developed bacterial peritonitis.
      Conventional attempts to remove the catheter by transcutaneous pulling failed and
      we thus decided to perform a median laparotomy to remove the catheter surgically.
      Intraoperatively an adhesion of the ascites drain (a so called 'basket catheter')
      to the mesentery very close to the small intestine was found, approximately 50 mm
      distal of the ligament suspensorium duodeni (ligament of Treitz). The basket
      catheter used for this patient was especially designed to drain infections, not
      fluids. We solved the adhesion, removed the basket catheter, placed a new
      surgical drain and finished the operation. The patient developed a rupture of his
      abdominal fascia suture 12 days later, which was caused by massive ascites and
      complicated by hepatorenal syndrome type I. The patient was taken to the
      operating theater again. After the second operation, the chronic liver failure
      decompensated and the patient died. Ascites caused by liver cirrhosis is still a
      medical challenge. The indication for the use of the correct percutaneous
      catheter for permanent paracentesis should be carefully considered. Some
      catheters are obviously not suited to drain ascites and may lead to fatal
      outcomes. 

PMID- 24453506
TI  - Observational Study to Assess the Therapeutic Value of Four Ovarian
      Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH
      Antagonists in Normally Responding Women.
AB  - OBJECTIVE: To compare the clinical results of four different protocols of COH for
      IVF-ICSI in normovulatory women, using in all cases pituitary suppression with
      GnRH antagonists. MATERIALS/METHODS: A single center, open label, parallel
      controlled, prospective, post-authorization study under the approved conditions
      for use where 305 normal responders women who were candidates to COH were
      assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed
      dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n =
      75, Group IV) to subsequently undergo IVF-ICSI. RESULTS: During stimulation,
      Group IV needed significantly more days of stimulation as compared to Group II
      [8.09 +/- 1.25 vs. 7.62 +/- 1.17; P < 0.05], but was the group in which more
      oocytes were recovered [Group I: 9.43 +/- 4.99 vs. Group II: 8.96 +/- 4.82 vs.
      Group III: 8.78 +/- 3.72 vs. Group IV: 11.62 +/- 5.80; P < 0.05]. No significant
      differences were seen between the groups in terms of clinical and ongoing
      pregnancy, but among patients in whom two embryos with similar quality parameters
      (ASEBIR) were transferred, the group treated with hp-hMG alone achieved a
      significantly greater clinical pregnancy rate as compared to all other groups
      [Group I: 31.6%, Group II: 56.4%, Group III: 28.7%, Group IV: 32.7%; P < 0.05].
      CONCLUSIONS: Although randomized clinical trials should be conducted to achieve a
      more reliable conclusion, these observations support the concept that stimulation
      with hp-hMG could be beneficial in normal responders women undergoing pituitary
      suppression with GnRH antagonists.

PMID- 24453505
TI  - Comparing the metal concentration in the hair of cancer patients and healthy
      people living in the malwa region of punjab, India.
AB  - The cancer prevalence in the Malwa region of Punjab (1089/million/year) is much
      higher than the national average cancer prevalence in India (800/million/year).
      The participants in the present study were 50 healthy individuals and 49 cancer
      patients all living in the Malwa region of Punjab, with the healthy people being
      selected from the same household as the cancer patients. High concentrations of
      several potentially toxic elements were found in hair samples from people living
      in Punjab. Compared to standard reference ranges, the metals in excess in both
      the control and patient groups were aluminium (Al), barium (Ba), manganese (Mn),
      strontium (Sr) and uranium (U). The most significant findings were high lead
      (Pb), U and Ba concentrations. The maximum values for Ba, Mn, Pb and U were found
      in hair from breast cancer patients. The mean concentration of U in hair from the
      breast cancer patients was 0.63 MUg U/g, which is more than double the value
      found in the control group and over six times higher than the reference range of
      0.1 MUg U/g. Water, soil, and phosphate fertilizers all seem to play a potential
      role, causing an increased metal burden in Punjabi people living in the Malwa
      region. The present study indicates that metals, and especially U, may be a
      factor in the development of breast cancer among Punjabi women. 

PMID- 24453507
TI  - Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with
      Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common
      endocrinopathies affecting women in the reproductive age group, and is one of the
      most common causes of hyperandrogenic anovulatory infertility. The aromatase
      inhibitor, letrozole, has been used for induction of ovulation. The purpose of
      this study was to compare the effects of letrozole and clomiphene citrate in
      induction of ovulation among patients with PCOS undergoing intrauterine
      insemination. METHODS: In a double-blind randomized study, 60 infertile patients
      with PCOS received standard doses of either clomiphene citrate or letrozole as an
      induction protocol prior to intrauterine insemination. A hormonal profile, pelvic
      ultrasound, hysterosalpingogram, and/ or laparoscopy were done for all patients.
      The patients were monitored for ovulation by translational ultrasonographic
      folliculometry, with measurement of number and size of the follicles, as well as
      endometrial thickness. Human chorionic gonadotrophin (HCG) was injected
      intramuscularly when at least one mature follicle >=18 mm diameter was detected,
      and intrauterine insemination was performed 32-36 hours later. Transvaginal
      ultrasound and beta-HCG measurement were performed for confirmation of pregnancy.
      RESULTS: Letrozole and clomiphene citrate achieved follicle maturation within a
      mean +/- standard deviation (SD) of 13.2 +/- 1.53 and 14.1 +/- 1.35 days,
      respectively, showing no significant difference (P > 0.05). The mean number of
      follicles reaching >=18 mm on the day of HCG administration was significantly
      higher in patients who received clomiphene citrate (2.9 +/- 1.77) than in those
      receiving letrozole (1.2 +/- 0.9). Letrozole had a significantly greater effect
      than clomiphene citrate on endometrial thickness (9.16 +/- 1.36 versus 4.46 +/-
      1.71). The number of pregnancies achieved in the letrozole group was
      significantly (P < 0.05) greater than in the clomiphene group. CONCLUSION:
      Letrozole in patients with PCOS is as effective as clomiphene citrate in inducing
      ovulation, and although the number of follicles produced by induction with
      letrozole were less than those produced by clomiphene, letrozole had a
      significantly greater effect on endometrial thickness than clomiphene citrate,
      and the incidence of pregnancy after intrauterine insemination was significantly
      higher, with a lower incidence of multiple pregnancy.

PMID- 24453508
TI  - Pregnancy related complications in patients with systemic lupus erythematosus, an
      egyptian experience.
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) has a tendency to occur in women
      in their reproductive years, causing complications during pregnancy and labour.
      Conversely, pregnancy can cause flares of disease activity, often necessitating
      immediate intervention. AIM OF STUDY: to study pregnancy related complications in
      patients with SLE. PATIENTS AND METHODS: The study included 48 SLE pregnant
      females. 27 patients with 38 pregnancies, their data viewed retrospectively from
      medical records, and 21 patients with 21 pregnancies followed up prospectively.
      The laboratory data included ANA, DNA, APL antibodies and anti Ro/SSA. The
      disease activity was calculated according to the Systemic Lupus Activity Measure.
      Ultrasound was performed to confirm gestational age and assess for the presence
      of any congenital fetal malformations, and then repeated monthly to detect any
      abnormality including intrauterine growth restriction. At 30 weeks gestation and
      onwards, assessment of fetal wellbeing including daily fetal kick chart and once
      weekly non stress test was performed. Doppler blood flow velocimetry was done for
      those with abnormal fetal heart rate pattern. After labour, the neonate was
      examined for complications including complete heart block and neonatal lupus.
      RESULTS: Anti dsDNA was found in 95% of the patients, anti Ro/SSA in 6% and anti
      APL in 30%. 57% of the patients followed up prospectively had active disease in
      the 1st trimester, 24% in the 2nd and 62% in the 3rd trimester. The most common
      maternal complication was preeclampsia 33%, followed by spontaneous abortion 20%.
      Prematurity was the most common fetal complication 37%, followed by intrauterine
      growth restriction 29%. 2 neonates were born with congenital heart block and 1
      with neonatal lupus. CONCLUSION: Pregnancy in SLE patients is associated with a
      higher risk of obstetric complications affecting both the mother and the fetus.
      Preeclampsia was the most common complication followed by prematurity.
      Preeclampsia was significantly associated with third trimester disease activity.

PMID- 24453510
TI  - Comparison between Cleavage Stage versus Blastocyst Stage Embryo Transfer in an
      Egyptian Cohort Undergoing in vitro Fertilization: A Possible Role for Laser
      Assisted Hatching.
AB  - BACKGROUND: Extended in vitro embryo culture and blastocyst transfer have emerged
      as essential components of the advanced reproductive technology armamentarium,
      permitting selection of more advanced embryos considered best suited for
      transfer. AIM OF STUDY: The aim of this study was to compare between cleavage
      stage and blastocyst stage embryo transfer in patients undergoing
      intracytoplasmic sperm injection, and to assess the role of assisted hatching
      technique in patients undergoing blastocyst transfer. PATIENTS AND METHODS: This
      study was carried out on two groups. Group I: 110 patients who underwent 120
      cycles of intracytoplasmic sperm injection with day 2-3 embryo transfer-for
      unexplained infertility or male factor within the previous 3 years. Their data
      obtained retrospectively from medical records. Group II: 46 age matched infertile
      female patients undergoing 51 intracytoplasmic sperm injection cycles for similar
      causes. Patients in Group II were further subdivided into 2 equal subgroups;
      Group IIa (23 patients), which had laser assisted hatching and Group IIb (23
      patients), which did not have assisted hatching. All patients had an infertility
      workup including basal hormonal profile, pelvic ultrasound, hysterosalpingogram
      and/or laparoscope and semen analysis of the patient's partner. All patients
      underwent controlled ovarian hyperstimulation: Using long protocol of ovulation
      induction. Laser assisted hatching was done for blastocysts of 23 patients.
      RESULTS: Comparison between both groups as regards the reproductive outcome
      showed a significant difference in pregnancy and implantation rates, both being
      higher in group II (P < 0.05) Comparison between both subgroups as regards the
      reproductive outcome showed a highly significant difference in pregnancy and
      implantation rates, both being higher in Group IIa (P < 0.01). There was also a
      significantly higher rate of multiple pregnancies among Group IIa (P < 0.05).
      CONCLUSION: Blastocyst transfer is a successful and improved alternative for
      patients with multiple failed in vitro fertilization attempts, associated with a
      significant increase in pregnancy and implantation rates. Furthermore, laser
      assisted hatching increases implantation and clinical pregnancy rates.

PMID- 24453509
TI  - Efficacy of dapoxetine in the treatment of premature ejaculation.
AB  - INTRODUCTION: Premature ejaculation (PE) is a common male sexual disorder which
      is associated with substantial personal and interpersonal negative psychological
      factors. Pharmacotherapy of PE with off-label antidepressant SSRI drugs is
      common. Development and regulatory approval of drugs specifically for the
      treatment of PE will reduce reliance on off-label treatments and serve to fill a
      unmet treatment need. AIM: To review evidence supporting the efficacy and safety
      of dapoxetine in the treatment of PE. METHODS: MEDLINE and the proceedings of
      major international and regional scientific meetings during the period 1994-2010
      were searched for publications or abstracts using the word dapoxetine in the
      title, abstract or keywords. This search was then manually cross-referenced for
      all papers. This review encompasses studies of dapoxetine pharmacokinetics,
      animal studies, human phase 1, 2 and 3 efficacy and safety studies and drug
      interaction studies. RESULTS: Dapoxetine is a potent selective serotonin re
      uptake inhibitor, which is administered on-demand 1-3 hours prior to planned
      sexual contact. Dapoxetine is rapidly absorbed and eliminated, resulting in
      minimal accumulation and has dose-proportional pharmacokinetics, which are
      unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in 5
      randomized, double-blind, placebo-controlled studies in 6081 men aged >=18 years.
      Outcome measures included stopwatch-measured intravaginal ejaculatory latency
      time (IELT), Premature Ejaculation Profile (PEP) inventory items, clinical global
      impression of change (CGIC) in PE, and adverse events. Mean IELT, all PEP items
      and CGIC improved significantly with both doses of dapoxetine vs. placebo (P <
      0.001 for all). The most common treatment related adverse effects included nausea
      (11.0% for 30 mg, 22.2% for 60 mg), dizziness (586% for 30 mg, 10.9% for 60 mg),
      and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated
      scales demonstrated no SSRI class-related effects with dapoxetine use.
      CONCLUSION: Dapoxetine, as the first drug developed for PE, is an effective and
      safe treatment for PE and represents a major advance in sexual medicine.

PMID- 24453511
TI  - The new extended-cycle levonorgestrel-ethinyl estradiol oral contraceptives.
AB  - Effective contraceptive counseling requires an understanding of a woman's
      preferences and medical history as well as the risks, benefits, side effects, and
      contraindications of each contraceptive method. Hormonal contraceptives using a
      variety of delivery methods are highly effective and this review highlights the
      new extended-cycle levonorgestrel-ethinyl estradiol contraceptives. Extended
      cycle OCPs are unique in offering fewer or no withdrawal bleeds over the course
      of one year but providers need to carefully counsel women regarding the initial
      increased breakthrough bleeding. Extended-cycle OCPs may be of particular benefit
      in women with medical comorbidities who would benefit from less withdrawal
      bleeds, those desiring to avoid monthly menses due to increased hormonal
      withdrawal symptoms, or simply women who don't desire a monthly period. The risks
      associated with all extended-cycle OCPs have been found to be similar to those of
      traditional OCPs therefore counseling on the risks and side effects is comparable
      to that of any combined hormonal contraceptives. Newer extended-cycle regimens
      shorten or eliminate the hormone-free interval, decrease frequency of menses to
      four times per year or eliminate menses altogether. This can reduce the risk of
      common menstrual symptoms, endometriosis, or severe dysmenorrhea by offering
      potentially greater ovarian suppression and preventing endogenous estradiol
      production while still providing highly effective, rapidly reversible, and safe
      contraception. 

PMID- 24453512
TI  - Monitoring maternal Beta carotene and retinol consumption may decrease the
      incidence of neurodevelopmental disorders in offspring.
AB  - Retinoic acids (13-cis and 13-trans) are known teratogens, and their precursor is
      retinol, a form of vitamin A. In 1995, Rothman et al demonstrated an association
      between excessive vitamin A, >10,000 IU/day, during the first trimester of
      pregnancy and teratogenic effects, particularly in the central nervous system.
      However, vitamin A deficiency has long been known to be deleterious to the mother
      and fetus. Therefore, there may be a narrow therapeutic ratio for vitamin A
      during pregnancy that has not previously been fully appreciated.
      Neurodevelopmental disorders may not be apparent by macroscopic brain examination
      or imaging, and proving the existence of a behavioral teratogen is not
      straightforward. However, an excess of retinoic acid and some neurodevelopmental
      disorders are both associated with abnormalities in cerebellar morphology.
      Physical and chemical evidence strongly supports the notion that beta carotene
      crosses the placenta and is metabolized to retinol. Only very limited amounts of
      beta carotene are stored in fetal fat cells as evidenced by the fact that
      maternal fat is yellow from beta carotene, whereas non-brown neonatal fat is
      white. Furthermore, newborns of carotenemic mothers do not share the yellow
      complexion of their mothers. The excess 13-trans retinoic acid derived from
      metabolized beta carotene in the fetus increases the concentration of the more
      teratogenic 13-cis retinoic acid since the isomerization equilibrium is shifted
      to the left. Therefore, this paper proposes that consideration be given to
      monitoring all potential sources of fetal 13-cis and 13-trans retinoic acid,
      including nutritional supplements, dietary retinol, and beta carotene,
      particularly in the first trimester of pregnancy. 

PMID- 24453513
TI  - The participation of prospective fathers in preconception care.
AB  - We present the data of male participants in the Coordinating Center of the
      Hungarian Preconception Service (HPS), Budapest, 1984-2010. One of main
      objectives of the HPS was the incorporation of male partners of female
      participants into the preparation of childbirth. The HPS is based on three steps:
      (I) Reproductive health check-up. (II) A 3-month preparation for conception with
      the major determinants of the development of new life such as sex, health and/or
      some diseases. Smoking and illicit drug use cessation and limitation of alcohol
      intake was suggested in the male participants (III) to achieve optimal conception
      and better protection of early pregnancy. Pregnant women usually visit prenatal
      care clinics between the 7th and 12th gestational week when it is too late to
      reduce the risk of congenital abnormalities. Male participation in HPS will help
      to enhance use of appropriate preconception methods at the appropriate time. 

PMID- 24453514
TI  - Trends in hysterectomy for genital prolapse: rural experience.
AB  - The present study was conducted to investigate the trends of vaginal hysterectomy
      for genital prolapse in last 20 years by analyzing case records of affected
      women. During the analysis period, 4831 women underwent hysterectomy; records of
      4223 (87.5%) were available. Of these, 911 (21.6%), 2.7% of 34,080 gynecological
      admissions, had vaginal hysterectomy for genital prolapse (study subjects).
      Eighty percent women who had vaginal hysterectomy for genital prolapse were over
      40 years of age; however, most of these women had had the disorder for years
      before they presented. Only 4 (0.4%) women had not given birth, 874 (96%) women
      had had two or more births, and 383 (42%) had had 5 or more births. Having given
      birth was the major factor responsible for genital prolapse. In all, 94.2% of
      women presented with something coming out of the vagina." Some women presented
      with abnormal vaginal bleeding or pain in abdomen as the chief complaint although
      they had had uterovaginal prolapse for years. There was no mortality and
      morbidity decreased over the years. There has been no change in the rate of
      vaginal hysterectomy for genital prolapse over the years. Surgical morbidity
      decreased trend, possibly because of the preoperative, intraoperative, and
      postoperative precautions taken, especially preoperative treatment of urinary and
      genital tract infection. Attempts need to be made to have safe births and a
      healthy life style so as to prevent genital prolapse and in case it occurs,
      therapy to prevent progression so that major interventions like hysterectomy are
      averted. Meticulous preoperative evaluation and planned therapy help in reducing
      surgical morbidity, if surgery becomes essential. 

PMID- 24453515
TI  - Preimplantation genetic testing in the 21st century: uncharted territory.
AB  - The past hundred years have given birth to arguably the most profound changes in
      society, medicine, and technology the world has ever witnessed. Genetics is one
      such field that has enjoyed a meteoric rise during this time. Progressing from
      Mendelian genetics to the discovery of DNA to the ability to sequence the human
      genome, perhaps no other discipline holds more promise to affect future change
      than genetics. Technology currently exists to evaluate some of the genetic
      information held by developing embryos in the context of an in vitro
      fertilization (IVF) cycle. This information is then used to determine which
      embryos are selected for uterine transfer. Many societies have enacted
      legislation to protect against possible abuses utilizing this technology.
      However, it is incumbent upon society to continue ensuring that preimplantation
      genetic diagnosis (PGD)-and genetic testing in general-is applied in a way that
      utilizes its potential in a responsible manner to improve health care. 

PMID- 24453516
TI  - Emerging options for emergency contraception.
AB  - Emergency post-coital contraception (EC) is an effective method of preventing
      pregnancy when used appropriately. EC has been available since the 1970s, and its
      availability and use have become widespread. Options for EC are broad and include
      the copper intrauterine device (IUD) and emergency contraceptive pills such as
      levonorgestrel, ulipristal acetate, combined oral contraceptive pills (Yuzpe
      method), and less commonly, mifepristone. Some options are available over-the
      counter, while others require provider prescription or placement. There are no
      absolute contraindications to the use of emergency contraceptive pills, with the
      exception of ulipristal acetate and mifepristone. This article reviews the
      mechanisms of action, efficacy, safety, side effects, clinical considerations,
      and patient preferences with respect to EC usage. The decision of which regimen
      to use is influenced by local availability, cost, and patient preference. 

PMID- 24453517
TI  - Preimplantation genetic screening: a practical guide.
AB  - The past several decades have seen tremendous advances in the field of medical
      genetics. The application of genetic technologies to the field of reproductive
      medicine has ushered in a new era of medicine that is likely to greatly expand in
      the coming years. Concurrent with an in vitro fertilization (IVF) cycle, it is
      now possible to obtain a cellular biopsy from a developing embryo and genetically
      evaluate this sample with increasing sophistication and detail. Preimplantation
      genetic screening (PGS) is the practice of determining the presence of aneuploidy
      (either too many or too few chromosomes) in a developing embryo. However, how and
      in whom PGS should be offered is a topic of much debate. 

PMID- 24453518
TI  - Ovarian Stem Cells-the Pros and Cons.
AB  - The potential for postnatal de novo oogenesis in mammals and in humans has become
      very controversial in the fields of reproductive science and biology.
      Historically, it has been thought that females of most mammalian species lose the
      ability to produce oocytes at birth. A contemporary understanding of stem cell
      biology together with novel experimental methods has challenged the model of a
      prenatal fixed ovarian primordial follicle pool that declines with age.
      Researchers have suggested replenishment of post-natal oocytes by germ-line stem
      cells (GSCs). According to this theory, GSCs produce oocytes and primordial
      follicles throughout the lifetime of the adult female. This review describes
      recent approaches supporting the revolutionary idea of de novo oogenesis in
      mammals and humans of reproductive-age and provides counter arguments from
      opponents of this novel and innovative concept. 

PMID- 24453519
TI  - Fertility preservation in gynecological cancers.
AB  - For cancers of reproductive system in women, fertility preservation is complex.
      Fertility is also affected by therapies, however prevention is possible.
      Radiotherapy affects gonads, uterus, and subsequent pregnancy outcomes in all
      ages. However, degree and damage depend on dose, irradiation field, and age at
      the time of exposure. Ovarian transposition is considered if ovarian involvement
      is unlikely. Gonadotoxic effects of chemotherapy are related to agent's type,
      cumulative doses, age, and ovarian reserve. Some agents are highly toxic.
      Rendering follicular development quiescent by suppression of gonadotropins does
      reduce the ovarian damage. Simple or radical trachelectomy can be used in early
      cervical cancer. Fertility saving surgery is possible only in early stage low
      grade epithelial cancers of the ovary, however, in germ cell tumors even in
      advanced stages it may be possible to preserve fertility. There are no standard
      recommendations for endometrial cancer. Embryo, oocyte, and ovarian tissue
      cryopreservation are possible. The human embryo is very resistant to damage. In
      view of these possibilities, it is advocated that attention to long term health
      and quality of life in gonadotoxic therapy must be incorporated into plans as
      early as possible. 

PMID- 24453520
TI  - Fertility preservation options after gonadotoxic chemotherapy.
AB  - Chemotherapy has the potential to deplete and destroy a woman's reproductive
      potential. Although many oncologists are referring women for fertility
      preservation before chemotherapy, in many cases there is limited time for
      fertility preservation. This review provides an overview of the impact of cancer
      and chemotherapy on the ovarian reserve, a summary of methods of fertility
      preservation prior to chemotherapy, and current knowledge of fertility
      preservation techniques after gonadotoxic chemotherapy. 

PMID- 24453522
TI  - Live birth from previously vitrified oocytes, after trophectoderm biopsy,
      revitrification, and transfer of a euploid blastocyst.
AB  - Our objective is to describe a successful live birth from oocyte vitrification
      followed by thaw, fertilization, blastocyst culture, trophectoderm biopsy,
      vitrification, and subsequent thaw. Fifteen mature oocytes were frozen from a
      patient with uterine factor infertility. Thirteen oocytes survived the thaw, and
      five underwent trophectoderm biopsy and were refrozen. Three euploid embryos were
      obtained. A single euploid embryo was transferred in the second thaw cycle to a
      known recipient leading to the delivery of a normal male infant. This case report
      is proof of the concept that preimplantation screening and diagnosis is an option
      for fertility preservation patients. 

PMID- 24453521
TI  - Robotics in Gynecology: Why is this Technology Worth Pursuing?
AB  - Robotic laparoscopy in gynecology, which started in 2005 when the Da Vinci
      Surgical System (Intuitive Surgical Inc) was approved by the US Food and Drug
      Administration for use in gynecologic procedures, represents today a modern,
      safe, and precise approach to pathology in this field. Since then, a great deal
      of experience has accumulated, and it has been shown that there is almost no
      gynecological surgery that cannot be approached with this technology, namely
      hysterectomy, myomectomy, sacrocolpopexia, and surgery for the treatment of
      endometriosis. Albeit no advantages have been observed over conventional
      laparoscopy and some open surgical procedures, robotics do seem to be
      advantageous in highly complicated procedures when extensive dissection and
      proper anatomy reestablishment is required, as in the case of oncologic surgery.
      There is no doubt that implementation of better logistics in finance, training,
      design, and application will exert a positive effect upon robotics expansion in
      gynecological medicine. Contrary to expectations, we estimate that a special
      impact is to be seen in emerging countries where novel technologies have resulted
      in benefits in the organization of health care systems. 

PMID- 24453523
TI  - Aromatic amino Acid decarboxylase deficiency not responding to pyridoxine and
      bromocriptine therapy: case report and review of response to treatment.
AB  - Aromatic L-amino acid decarboxylase (AADC) deficiency (MIM #608643) is an
      autosomal recessive inborn error of monoamines. It is caused by a mutation in the
      DDC gene that leads to a deficiency in the AADC enzyme. The clinical features of
      this condition include a combination of dopamine, noradrenaline, and serotonin
      deficiencies, and a patient may present with hypotonia, oculogyric crises,
      sweating, hypersalivation, autonomic dysfunction, and progressive encephalopathy
      with severe developmental delay. We report the case of an 8-month-old boy who
      presented with the abovementioned symptoms and who was diagnosed with AADC
      deficiency based on clinical, biochemical, and molecular investigations.
      Treatment with bromocriptine and pyridoxine showed no improvement. These data
      support the findings observed among previously reported cohorts that showed poor
      response of this disease to current regimens. Alternative therapies are needed to
      ameliorate the clinical complications associated with this disorder. 

PMID- 24453524
TI  - Changes in pain perception in women during and following an exhaustive
      incremental cycling exercise.
AB  - Exercise has been found to alter pain sensitivity with a hypoalgesic response
      (i.e., diminished sensitivity to pain) typically reported during and/or following
      high intensity exercise. Most of this research, however, has involved the testing
      of men. Thus, the purpose of the following investigation was to examine changes
      in pain perception in women during and following exercise. Seventeen healthy
      female subjects (age 20.47+/-.87; VO2 peak 36.77+/- 4.95) volunteered to undergo
      pain assessment prior to, during, and after a graded exhaustive VO2 peak cycling
      challenge. Heart Rate (HR) and Oxygen Uptake (VO2) were monitored along with
      electro-diagnostic assessments of Pain Threshold (PT) and Pain Tolerance (PTOL)
      at: 1) baseline (B), 2) during exercise (i.e., 120 Watts), 3) at exhaustive
      intensity (VO2 peak), and 4) 10 minutes into recovery (R). Data were analyzed
      using repeated measures ANOVA to determine differences across trials. Significant
      differences in PT and PTOL were found across trials (PT, p = 0.0043; PTOL p =
      0.0001). Post hoc analyses revealed that PT were significantly elevated at VO2
      peak in comparison to B (p = 0.007), 120 Watts (p = 0.0178) and R (p = 0.0072).
      PTOL were found to be significantly elevated at 120 Watts (p = 0.0247), VO2 peak
      (p < 0.001), and R (p = 0.0001) in comparison to B. In addition, PTOL were found
      to be significantly elevated at VO2 peak in comparison to 120 Watts (p = 0.0045).
      It is concluded that exercise-induced hypoalgesia occurs in women during and
      following exercise, with the hypoalgesic response being most pronounced following
      exhaustive exercise. Key PointsExercise-induced hypoalgesia (i.e., elevated PT
      and PTOL) was found to occur in women during and following exercise, with the
      hypoalgesic response being most pronounced during exhaustive exercise. 

PMID- 24453526
TI  - An innovative ski-boot: design, numerical simulations and testing.
AB  - The present work is concerned with the design of an innovative ski-boot. In order
      to optimize ergonomics and biomechanical behavior of the ski-boot it is important
      to take into account the orientation of the leg with respect to the ground. The
      SGS system (Stance Geometry System) developed in this work allows the skier to
      adjust for posture in the frontal plane by rotating the sole of the boot about
      the antero-posterior axis (ski-boot is then locked in the desired position before
      skiing). A simplified model of the effect of ski-boot deformation on skiing
      behavior is used to evaluate the minimal stiffness the system must have. An
      experimental analysis on the ski slopes was carried out to provide ski-boot
      deformations and loading data in different skiing conditions, to be used in
      numerical simulations. Finite Elements Method (FEM) simulations were performed
      for optimal design of the joint between ski-boot and sole. The active loads and
      local ski-boot deformations during small- and large-radius turns were
      experimentally determined and used to validate a FEM model of the ski-boot. The
      model was used to optimize the design for maximum stiffness and to demonstrate
      the efficacy of virtual design supported by proper experimental data. Mean loads
      up to 164% body weight were measured on the outer ski during turning. The new SGS
      design system allows the adjustment of lateral stance before using the ski-boot,
      optimizing the ski-boot stiffness through FEM analysis. Innovative aspects of
      this work included not only the stance geometry system ski-boot but also the
      setup of a virtual design environment that was validated by experimental
      evidence. An entire dataset describing loads during skiing has been obtained. The
      optimized SGS ski-boot increases intrinsic knee stability due to proper
      adjustment of lateral stance, guaranteeing appropriate stiffness of the ski-boot
      system. Key PointsLoad acting during different phases of active skiing have been
      investigated in both qualitative and quantitative ways.The effects of ski-boot -
      ski-boot sole stiffness during skiing has been investigated.A ski-boot stance
      geometry system and an innovative design environment have been developed to make
      skiing easier and safer. 

PMID- 24453525
TI  - Personality Does not Influence Exercise-Induced Mood Enhancement Among Female
      Exercisers.
AB  - The present study investigated the influence of personality on exercise-induced
      mood changes. It was hypothesised that (a) exercise would be associated with
      significant mood enhancement across all personality types, (b) extroversion would
      be associated with positive mood and neuroticism with negative mood both pre- and
      post-exercise, and (c) personality measures would interact with exercise-induced
      mood changes. Participants were 90 female exercisers (M = 25.8 yr, SD = 9.0 yr)
      who completed the Eysenck Personality Inventory (EPI) once and the Brunel Mood
      Scale (BRUMS) before and after a 60-minute exercise session. Median splits were
      used to group participants into four personality types: stable introverts (n =
      25), stable extroverts (n = 20), neurotic introverts (n = 26), and neurotic
      extroverts (n = 19). Repeated measures MANOVA showed significant mood enhancement
      following exercise across all personality types. Neuroticism was associated with
      negative mood scores pre- and post-exercise but the effect of extroversion on
      reported mood was relatively weak. There was no significant interaction effect
      between exercise-induced mood enhancement and personality. In conclusion,
      findings lend support to the notion that exercise is associated with improved
      mood. However, findings show that personality did not influence this effect,
      although neuroticism was associated with negative mood. Key PointsResearch in
      general psychology has found that stable personality trait are associated changes
      in mood states. Ninety females exercisers completed a personality test and mood
      scales before and after exercise. Results indicated mood changes were not
      associated with personality, although neuroticism was associated with negative
      mood. 

PMID- 24453527
TI  - Inspiratory muscle fatigue following moderate-intensity exercise in the heat.
AB  - Heavy exercise has been shown to elicit reductions in inspiratory muscle strength
      in healthy subjects. Our purpose was to determine the combined effects of
      moderate-intensity endurance exercise and a thermal load on inspiratory muscle
      strength in active subjects. Eight active, non heat-acclimatized female subjects
      (23.5 +/- 1.4 yr; VO2max = 39.8 +/- 2.4 ml.kg(-1).min(-1)) randomly performed two
      40 min endurance exercise bouts (60% VO2max) in either a thermo-neutral (22
      degrees C/21% RH) or hot (37 degrees C/33% RH) environment on separate days.
      Maximal sustained inspiratory mouth pressure (PImax) was obtained pre and post
      exercise as an index of inspiratory muscle strength. Additional variables
      obtained every 10 min during the endurance exercise bouts included: rectal
      temperature (TRE), heart rate (HR), minute ventilation (VE), oxygen uptake (VO2),
      tidal volume (VT), breathing frequency (Fb), and ratings of perceived exertion
      and dyspnea (RPE/RPD). Data were analyzed with repeated measures ANOVA. PImax was
      significantly reduced (p < 0.05) after exercise in the hot environment when
      compared to baseline and when compared to post exercise values in the thermo
      neutral environment. PImax was unchanged from baseline following exercise in the
      thermo-neutral environment. HR and TRE were significantly higher (p < 0.05) in
      the hot compared to the thermo-neutral environment. VE and VO2 were not
      significantly different between conditions. VT was unchanged between conditions
      whereas Fb was higher (p < 0.05) in the hot condition compared to thermo-neutral.
      RPE was not significantly different between conditions. RPD was significantly
      higher (p < 0.05) in the hot compared to the thermo-neutral environment. We
      conclude that moderate-intensity endurance exercise (60% VO2max) in a hot
      environment elicits significant reductions in inspiratory muscle strength in
      unfit females. This finding is novel in that previous studies conducted in a
      thermo-neutral environment have shown that an exercise intensity of >80% VO2max
      is required to elicit reductions in inspiratory muscle strength. In addition,
      dyspnea perception during exercise is greater in a hot environment, compared to
      thermo-neutral, at a similar level of VE and VO2. Key PointsThe combined effects
      of a heat load and exercise on inspiratory muscle strength were investigated in
      untrained female subjects.Previous studies have shown that a very high exercise
      intensity (> 80% VO2max) is required to elicit reductions in inspiratory muscle
      strength.Prolonged submaximal exercise (40-min/60% VO2max) in a hot environment
      significantly reduced inspiratory muscle strength in untrained females whereas
      the same intensity in a thermo-neutral environment had no effect on inspiratory
      muscle function.These reductions in inspiratory muscle strength may be related to
      competition for blood flow among the locomotor, inspiratory, and cutaneous
      circulations. 

PMID- 24453528
TI  - Doping and performance enhancing drug use in athletes living in sivas, mid
      anatolia: a brief report.
AB  - The aim of this study was to determine the rate of doping and performance
      enhancing drug use in athletes in Sivas, Turkey, and to analyze the main reasons
      for the use. This was a cross-sectional study based on a self-report
      questionnaire. The subjects filled the questionnaires under the supervision of
      the investigators during interviews. This questionnaire included 24 items
      describing the population in terms of demographics, sport practice, doping in
      sport and substance use. Moreover, we assessed the frequency of doping drug use.
      The number of respondents was 883, of which 433 athletes and 450 healthy non
      athletes (control group). The mean age of the total volunteers was 21.8 +/- 3.7
      yrs. The male and female ratios were 78.2% and 21.8% respectively. Doping and
      performance enhancing drug usage rate was 8.0% (71cases in 883 subjects). Doping
      drug use among the athletes was significantly (p < 0.05) higher (14.5%) compared
      with the non-athletes (1.8%). The agents used were anabolic steroids in 60.5%, l
      carnitene in 12.7%, erythropoietin in 5.4%, Na-bicarbonate in 11.3% and
      creatinine in 14.1% of 71 cases. The reasons for doping use were to have a better
      body condition in 34 cases (47.9%) and to solve weight (gaining or loosing)
      problems in 8 (11.3%) cases. Since the potential side effects of doping drugs are
      not satisfactorily familiar to the most users, the education of athletes on the
      matter must be a top priority. Key PointsDoping and performance enhancing drug
      use was 71 (8.0%) in 883 subjects, and it was significantly higher (14.5%) in the
      athletes compared with the non-athletes (1.8%) in Sivas, Turkey.The rate of
      athletes who experienced such drugs at least once in their life was 29.0%.The
      52.4% of doping and performance enhancing drug users accepted that they were
      unaware of the drugs full and/or potential side effects. 

PMID- 24453529
TI  - Nutrient intakes of men and women collegiate athletes with disordered eating.
AB  - The objective of this study was to assess the macro- and micronutrient intakes of
      men and women collegiate athletes with disordered eating behaviors and to compare
      the nutrient intakes of athletes with restrictive- versus binge-eating behaviors.
      National Collegiate Athletic Association (NCAA) Division I University athletes (n
      = 232) were administered an anonymous, written questionnaire to compare nutrient
      intakes, desired weight change, and weight control behaviors in athletes with
      restrictive- (R) and binge- (B) eating behaviors to those in asymptomatic (A)
      athletes. T-tests, chi(2) statistic, and ANOVA were used to test for differences
      among disordered eating groups within genders (p < 0.05). Data are means +/-
      standard error of the mean. Among men athletes, those with disordered eating
      consumed a smaller percentage of energy from carbohydrate compared to controls (R
      = 49.7 +/- 1.5; B = 48.7 +/- 2.3; A = 53.4 +/- 0.7%). Among female athletes,
      those with disordered eating wanted to lose a greater percentage of their current
      body weight than did asymptomatic athletes (B = -6.1 +/- 1.4; R = -6.7 +/- 1.1; A
      = -3.7 +/- 0.4%). Women who were classified with binge eating consumed
      significantly more alcohol than did controls (B = 6.8 +/- 1.3; A = 3.9 +/- 0.4 g
      alcohol per day). Athletes with disordered eating were more likely to report
      restricting their intake of carbohydrate and fat and using supplements to control
      their weight than asymptomatic athletes. Disordered eating was not associated
      with greater frequencies of inadequate micronutrient intake in either gender.
      Athletes with disordered eating may be at significantly greater risk for
      nutritional inadequacies than athletes who are asymptomatic due to macronutrient
      restriction and greater alcohol consumption. Key PointsAthletes with disordered
      eating were more likely to report restricting their intake of carbohydrate and
      fat and using supplements to control their weight than asymptomatic athletesAmong
      female athletes, those with disordered eating wanted to lose a greater percentage
      of their current body weight than did asymptomatic athletesDisordered eating was
      not associated with greater frequencies of inadequate micronutrient intake in
      either genderAthletes with disordered eating may be at significantly greater risk
      for nutritional inadequacies than athletes who are asymptomatic due to
      macronutrient restriction and greater alcohol consumption. 

PMID- 24453530
TI  - Effects of functional electric stimulation cycle ergometry training on lower limb
      musculature in acute sci individuals.
AB  - The purpose of this study was to compare three different intervals for a between
      sets rest period during a common isokinetic knee extension strength-testing
      protocol of twenty older Brazilian men (66.30 +/- 3.92 yrs). The volunteers
      underwent unilateral knee extension (Biodex System 3) testing to determine their
      individual isokinetic peak torque at 60, 90, and 120 degrees  .s-1. The
      contraction speeds and the rest periods between sets (30, 60 and 90 s) were
      randomly performed in three different days with a minimum rest period of 48
      hours. Significant differences between and within sets were analyzed using a One
      Way Analysis of Variance (ANOVA) with repeated measures. Although, at angular
      velocity of 60 degrees .s-1 produced a higher peak torque, there were no
      significant differences in peak torque among any of the rest periods. Likewise,
      there were no significant differences between mean peak torque among all resting
      periods (30, 60 and 90s) at angular velocities of 90 and 120 degrees .s-1. The
      results showed that during a common isokinetic strength testing protocol a
      between set rest period of at least 30 s is sufficient for recovery before the
      next test set in older men. Key PointsMuscle fiber cross sectional area (CSAf )
      decreased 38% following spinal cord injury (SCI).Early intervention with
      functional electric stimulation cycle ergometry (FES-CE) prevented further loss
      of CSAf in SCI patients and increased power output.Muscle myosin heavy chain
      (MHC) and myonuclear density were unaffected by SCI or FES-CE. 

PMID- 24453531
TI  - Adolescent athletes and the demand and supply of drugs to improve their
      performance.
AB  - The aim of this study was to gather information into the principal methods and
      means employed to supply adolescents with doping agents and others substances
      used to improve their sporting performance. We conducted a nation wide study in
      France among adolescent athletes, using a self-completed questionnaire.
      Exploitable questionnaires (n = 6402) were returned, corresponding to 48.9% for
      the girls and 51.1% for the boys, both aged on average from 16.1 +/- 2.2 years.
      These adolescents practise on average 10.0 +/- 5.2 hours of sport per week. 21.9%
      participate on a national or international competition level. Of our respondents,
      4.0% (95% confidence interval: 3.5% - 4.5%) say they have been enticed into using
      products which are prohibited for athletes. 10.3% of the adolescents say that
      they have received substances to improve their performance at least once from an
      average of two different people. It was mostly a friend, their parents and the
      family doctor. On average, in 33.2% of the cases, the adolescent received the
      product without asking for it, and in nearly half the cases (46.6%), the
      adolescent paid for the product. We feel that it is necessary to better
      understand the ways in which this black market functions: for example; the
      initial sources of the products sold, the number and the 'profiles' of the
      dealers, the general organisation of the market and the sums of money involved.
      Key PointsThis study confirms the existence of a 'black market' for products to
      improve performance, which is directed at adolescent athletes engaged in high
      level competitions.This market is characterized by its ease of accessibility and
      also the diversity of its 'suppliers', the two main sources being friends and
      parents. 

PMID- 24453532
TI  - Reproducibility of outdoor flat and uphill cycling time trials and their
      performance correlates with peak power output in moderately trained cyclists.
AB  - The aims of the present study were firstly to examine the reproducibility of
      outdoor flat and uphill cycling time trials (TT), and secondly to assess the
      relationship between peak power output (Wpeak) obtained in the laboratory and
      outdoor cycling performance in moderately trained cyclists. Eight competitive
      male cyclists first performed a progressive cycle ergometer test in the
      laboratory to determine Wpeak (W). Thereafter, they performed three 36 km TT
      (TT36) on a flat course on separate days and at the same time of the day. On a
      different day, they also performed three 1.4 km uphill TT (TT1.4) in a single
      day. The coefficient of variation (CV) values across three TT36 and TT1.4 ranged
      from 1.1 - 1.4% and 2.6 - 2.9%, for performance time (min) and mean power (W),
      respectively. The correlation between absolute Wpeak (W) obtained in the
      laboratory and mean power during TT36 and TT1.4 was 0.90 (p < 0.01) and 0.98 (p <
      0.01), respectively. Absolute Wpeak (W) correlated significantly with performance
      time in TT36 (r = -0.72, p < 0.05) but not in TT1.4 (r = -0.52, p > 0.05). The
      correlation between relative Wpeak (W.kg(-1)) and performance time in TT36 and
      TT1.4 was r = -0.65 (p > 0.05) and r = -0.91 (p < 0.01), respectively. In
      conclusion, under stable environmental conditions, performance time and mean
      power are highly reproducible in moderately trained cyclists during outdoor
      cycling TT. Laboratory determined absolute Wpeak (W) may predict cycling
      performance on a flat course but relative Wpeak (W.kg(-1)) is a better predictor
      of performance during uphill cycling. Key PointsUnder stable environmental
      conditions, performance time and mean power are highly reproducible in moderately
      trained cyclists during outdoor flat and uphill cycling time trials.Laboratory
      determined peak power output (Wpeak) (W) may predict cycling performance on a
      flat course.Laboratory determined relative Wpeak (W.kg(-1)) is a better predictor
      of performance during uphill cycling. 

PMID- 24453533
TI  - The effects of rest interval on quadriceps torque during an isokinetic testing
      protocol in elderly.
AB  - The purpose of this study was to compare three different intervals for a between
      sets rest period during a common isokinetic knee extension strength-testing
      protocol of twenty older Brazilian men (66.30 +/- 3.92 yrs). The volunteers
      underwent unilateral knee extension (Biodex System 3) testing to determine their
      individual isokinetic peak torque at 60, 90, and 120 degrees s(-1). The
      contraction speeds and the rest periods between sets (30, 60 and 90 s) were
      randomly performed in three different days with a minimum rest period of 48
      hours. Significant differences between and within sets were analyzed using a One
      Way Analysis of Variance (ANOVA) with repeated measures. Although, at angular
      velocity of 60 degrees s(-1) produced a higher peak torque, there were no
      significant differences in peak torque among any of the rest periods. Likewise,
      there were no significant differences between mean peak torque among all resting
      periods (30, 60 and 90s) at angular velocities of 90 and 120 degrees s(-1). The
      results showed that during a common isokinetic strength testing protocol a
      between set rest period of at least 30 s is sufficient for recovery before the
      next test set in older men. Key PointsThe assessment of muscular strength using
      isokinetics muscle contraction in older individuals is very important for
      exercise prescription and rehabilitation.The minimal time between intraset
      isokinetics knee extension assessment in older individuals need to be more
      investigated, however 30 s appear to besufficient time for strength recover. 

PMID- 24453534
TI  - Effects of A School-Based Intervention on BMI and Motor Abilities in Childhood.
AB  - Obesity in childhood is increasing worldwide. To combat overweight and obesity in
      childhood, the school-based Children's Health InterventionaL Trial (CHILT)
      project combines health education and physical activity. This paper examines the
      effect of intervention on the body mass index (BMI) and motor abilities after
      20.8 +/- 1.0 months in 12 randomly selected primary schools compared with 5
      randomly selected control schools. The anthropometric data were assessed, BMI was
      calculated. Coordination was determined by lateral jumping and endurance
      performance by a 6-minute run. No difference in the prevalence of overweight and
      obesity was found between the intervention (IS) and control schools (CS) either
      at baseline or following intervention (each p > 0.05). The increase in the number
      of lateral jumps was significantly higher in the IS than in the CS (p < 0.001).
      For the 6-minute run the increase in distance run was significantly improved in
      IS (p = 0.020). All variables were controlled for gender and age. Overweight and
      obese children in both IS and CS produced significantly lower scores in
      coordination and endurance tasks than normal and underweight children during both
      examinations (each p <= 0.001), adjusted for gender and age. Preventive
      intervention in primary schools offers an effective means to improve motor skills
      in childhood and to break through the vicious circle of physical inactivity -
      motor deficits - frustration - increasing inactivity possibly combined with an
      excess energy intake and weight gain. To prevent overweight and obesity these
      measures have to be intensified. Key PointsSchool-based prevention improves motor
      abilities in primary school children.The incidence of obesity is not influenced
      by school-based intervention.To prevent obesity in early childhood the measures
      have to be intensified and parents should be included. 

PMID- 24453535
TI  - Effect of strength and endurance training on cognition in older people.
AB  - The purpose of this study was to investigate the effect of moderate strength and
      endurance training on cognition evaluated by event-related potentials (ERP) in
      older people. Thirty-six adults, aged 60-85 years, were randomly divided into
      three groups: sedentary control (C), strength training (ST), and endurance
      training (ET). Participants performed functional fitness tests and ERP data were
      recorded before and after nine weeks of training. Training involved three
      sessions per week. Functional fitness test performance improved significantly in
      the ST and ET groups. The latencies of the N1, N2, and P2 components and the
      amplitudes of the N1P2, P2N2, and N2P3 components differed significantly between
      groups (p < 0.05). After training, the latencies of the P2 and N2 components at
      the Fz and Cz sites, decreased significantly, and the amplitudes of the N1P2,
      P2N2, and N2P3 components at the Fz site and the N1P2 and N2P3 components at the
      Cz site, increased significantly in the ST group compared with the ET group.
      After training, the latencies of N1, N2, and P2 components shortened
      significantly, and the amplitudes of the N1P2, P2N2, and N2P3 components
      increased significantly in the ST group compared with the C group. The latencies
      of the N2 and P2 components shortened significantly in the ET group compared with
      the C group, although the amplitudes of the ERP recordings did not differ
      significantly between groups. These data suggest that strength training might
      facilitate early sensory processing and cognitive functioning in older
      individuals. Key PointsStrength training may have facilitating effects on early
      information processing and cognition in older people.It is interesting that only
      small improvements in functional fitness affected cognitive performance.More
      research is needed to determine how the different exercise regimens contribute to
      discrete changes in CNS functioning and how such changes affect the P3 component
      of the ERP. 

PMID- 24453536
TI  - The prolonged intake of L-arginine-L-aspartate reduces blood lactate accumulation
      and oxygen consumption during submaximal exercise.
AB  - L-arginine-L-aspartate is widely used by athletes for its potentially ergogenic
      properties. However, only little information on its real efficacy is available
      from controlled studies. Therefore, we evaluated the effects of prolonged
      supplementation with L-arginine-L-aspartate on metabolic and cardiorespiratory
      responses to submaximal exercise in healthy athletes by a double blind placebo
      controlled trial. Sixteen healthy male volunteers (22 +/- 3 years) performed
      incremental cycle spiroergometry up to 150 watts before and after intake of L
      arginine-L-aspartate (3 grams per day) or placebo for a period of 3 weeks. After
      intake of L-arginine-L-aspartate, blood lactate at 150 watts dropped from 2.8 +/-
      0.8 to 2.0 +/- 0.9 mmol.l(-1) (p < 0.001) and total oxygen consumption during the
      3-min period at 150 watts from 6.32 +/- 0.51 to 5.95 +/- 0.40 l (p = 0.04)
      compared to placebo (2.7 +/- 1.1 to 2.7 +/- 1.4 mmol.l(-1); p = 0.9 and 6.07 +/-
      0.51 to 5.91 +/- 0.50 l; p = 0.3). Additionally, L-arginine-L-aspartate
      supplementation effected an increased fat utilisation at 50 watts. L-arginine and
      L-aspartate seem to have induced synergistic metabolic effects. L-arginine might
      have reduced lactic acid production by the inhibition of glycolysis and L
      aspartate may have favoured fatty acid oxidation. Besides, the results indicate
      improved work efficiency after L-arginine-L-aspartate intake. The resulting
      increases of submaximal work capacity and exercise tolerance may have important
      implications for athletes as well as patients. Key PointsAmino acids are among
      the most common nutritional supplements taken by athletes. They are involved in
      numerous metabolic pathways that affect exercise metabolism.Three weeks of L
      arginine-L-aspartate supplementation resulted in lower blood lactate
      concentrations and oxygen consumption, diminished glucose and enhanced fat
      oxidation, and reduced heart rate and ventilation during submaximal cycle
      exercise.This implies increased submaximal work capacity and exercise tolerance,
      which may have important implications for both athletes as well as patients. 

PMID- 24453537
TI  - Evaluation of unexplained dyspnea in a young athletic male with pectus excavatum.
AB  - Pectus excavatum (PE) is a relatively common congenital deformity of the anterior
      chest wall associated with reduced exercise capacity. Uncertainty exists over the
      nature of physiologic impairment in PE. Evidence suggests that myocardial
      compression exerted by the displaced sternum on the right heart chambers,
      disables the ability of the heart to augment stroke volume during exercise. This
      case study describes the evaluation of an athletic 20 year old Caucasian male,
      lifelong non-smoker, with severe pectus deformity and previous fixation procedure
      to repair a sternal fracture. The patient performed an incremental cycle
      ergometer exercise test to determine the etiology of his dyspnea with exertion.
      The patient demonstrated normal work output and normal aerobic capacity but
      displayed dynamic hyperinflation. Mechanical restriction of tidal volume
      expansion appeared to be the major contributors to exercise limitation. These
      results are compared and contrasted with similar cases reported in the
      literature. Key PointsPectus excavatum (PE) is a relatively common phenomenon
      affecting approximately 1 in 300 births, with a 9:1 ratio of male to female rate
      of incidence.The etiology or exercise limitation is most frequently due to
      cardiovascular limitation due to the compression of the sternum upon the
      myocardium, impairing the ability to augment stroke volume.The Pectus Severity
      Index (PSI) is a useful indicator of pectus severity.Cardiopulmonary exercise
      testing provides useful data to distinguish between cardiovascular limitation,
      ventilatory limitation, or deconditioning in the evaluation of PE.In this case
      study, ventilatory limitation was due to the mechanical restriction of the
      thoracic cavity. 

PMID- 24453538
TI  - An investigation of a reference posture used in determining rearfoot kinematics
      for both healthy and patellofemoral pain syndrome individuals.
AB  - The choice of a reference posture is important when investigating rearfoot motion
      in clinical populations. The reference posture used may affect the magnitude of
      the peak angles and therefore may not enable comparison of the rearfoot
      kinematics across different populations. This study examined the relationship
      between the rearfoot frontal plane pattern of motion and three reference postures
      during the stance phase of walking in healthy and patellofemoral pain syndrome
      (PFPS) subjects. The three reference postures investigated were: Relaxed Standing
      posture, subtalar joint neutral position (STJN) and when the calcaneus and the
      lower leg were vertically aligned (Vertical Alignment). The rearfoot
      inversion/eversion during the stance phase was measured in 14 healthy subjects
      and 13 subjects with diagnosed PFPS using three dimensional motion analysis with
      the three different reference postures. The graphs of rearfoot inversion/eversion
      motion were overlaid with the angle at the rearfoot in the static posture and any
      intersection between the static angle and rearfoot motion was noted. An ANOVA
      showed significant differences in static posture between the groups for Relaxed
      Standing (p = 0.01), and STJN (p = 0.02). For both groups, with Relaxed Standing
      as a reference posture, the mean rearfoot pattern of motion did not intersect the
      Relaxed Standing static angle during the stance phase. The use of Vertical
      Alignment reference posture, however, showed an intersection of this reference
      posture through the rearfoot pattern of motion. The use of the Vertical Alignment
      reference posture also generated a typical rearfoot motion pattern for both
      groups and therefore it may be an appropriate reference posture for both healthy
      and PFPS individuals. Key PointsThe use of the three reference postures resulted
      in shifting of the curve of the rearfoot frontal plane pattern of motion. The
      shift of the curve is important in identifying the magnitude of rearfoot peak
      motion during the stance phase.The use of Vertical Alignment reference posture
      only, generated a typical rearfoot motion pattern for both groups and therefore
      it may be an appropriate reference posture for both healthy and PFPS
      individualsThe use of Relaxed Standing and STJN as reference postures would not
      be recommended due to their poor test retest reliability. 

PMID- 24453539
TI  - The effect of cycling cadence on subsequent 10km running performance in well
      trained triathletes.
AB  - The aim of this study was to examine the effects of different pedalling cadences
      on the performance of a subsequent 10km treadmill run. Eight male triathletes
      (age 38.9 +/- 15.4 years, body mass 72.2 +/- 5.2 kg, and stature 176 +/- 6 cm;
      mean +/- SD) completed a maximal cycling test, one isolated run (10km), and then
      three randomly ordered cycle-run sessions (65 minutes cycling + 10km run). During
      the cycling bout of the cycle-run sessions, subjects cycled at an intensity
      corresponding to 70% Pmax while maintaining one of three cadences, corresponding
      to preferred cadence (PC), PC+15% (fast cadence) and PC-15% (slow cadence). Slow,
      preferred and fast cadences were 71.8 +/- 3.0, 84.5 +/- 3.6, and 97.3 +/- 4.3
      rpm, respectively (mean +/- SD). Physiological variables measured during the
      cycle-run and isolated run sessions were VO2, VE, RER, HR, RPE, and blood
      lactate. Biomechanical variables measured during the cycle-run and isolated run
      sessions were running velocity, stride length, stride frequency, and hip and knee
      angles at foot-strike and toe-off. Running performance times were also recorded.
      A significant effect of prior cycling exercise was found on 10km running time (p
      = 0.001) without any cadence effect (p = 0.801, omega(2) = 0.006) (49:58 +/-
      8:20, 49:09 +/- 8:26, 49:28 +/- 8:09, and 44:45 +/- 6:27 min.s(-1) for the slow,
      preferred, fast, and isolated run conditions, respectively; mean +/- SD).
      However, during the first 500 m of the run, running velocity was significantly
      higher after cycling at the preferred and fast cadences than after the slow
      cadence (p < 0.05). Furthermore, the slow cadence condition was associated with a
      significantly lower HR (p = 0.012) and VE (p = 0.026) during cycling than in the
      fast cadence condition. The results confirm the deterioration in running
      performance completed after the cycling event compared with the isolated run.
      However, no significant effect of cycling cadence on running performance was
      observed within the cadence ranges usually used by triathletes. Key
      PointsCompared with an isolated run, completion of a cycling event impairs the
      performance of a subsequent run independently of the pedalling cadence.The choice
      of cadence within triathletes' usual range does not seem to influence the
      performance of a 10km run.The results reinforce the necessity for triathletes to
      practice multi-block training in order to simulate the physiological responses
      experienced by the cycle-run transition.Further research into the effects of
      cycling cadence on subsequent running performance is required. 

PMID- 24453540
TI  - Resistance training improves sleep quality in older adults a pilot study.
AB  - Older individuals, as a group, tend to experience difficulty sleeping compared to
      younger adults. Improving sleep in the elderly would have beneficial public
      health consequences. This study utilized 8 sedentary, older adults, 78.1 +/- 3.1
      years of age, who participated in a six-month long resistance training (RT)
      program. The Pittsburgh Sleep Quality Index (PSQI) was used to examine sleep
      quality, and a 1 repetition max test (1-RM) was used to determine upper (bench
      press) and lower (leg press) body strength. Total strength, defined as the sum of
      the bench press and leg press 1-RM results, was also reported. The training
      resulted in significant improvements (p < 0.05) in total (19%) and upper body
      (52%) strength and in sleep quality (38%). Future studies should examine the
      effects of strength gain/loss and time-of-day training on sleep quality. Key
      PointsCompromised sleep and deterioration of skeletal muscle mass and function
      are commonly found among the aged.Results show that RT led to improvements in
      upper and total body strength in older participants who trained three times per
      week in the morning.The resistance training led to improvements in sleep as
      measured by a self-report sleep questionnaire, the Pittsburgh Sleep Quality
      Index.The small sample size used, lack of control group, and the fact that the
      participants on average were characterized as "good "sleepers at the study onset,
      necessitates that further investigation occur.We suggest that further research is
      required to explore the effects of RT performed at different times of the day as
      well as to determine the relationship between sleep gains or losses upon changes
      in sleep quality. 

PMID- 24453541
TI  - Broadening the definition of the genus Thalassaphorura Bagnall, 1949 (Collembola,
      Onychiuridae) with a new aberrant species from China.
AB  - A new species belonging to the tribe Thalassaphorurini, Thalassaphorura
      problematica sp. n., is described from Northeast China. The new species is
      closest to the large genus Thalassaphorura by its simple vesicles in PAO and its
      furcal rudiment, but it does not fit the definition of the genus by the absence
      of chaeta d0 on head, the number of chaetae in the distal whorl of tibiotarsi and
      the labium type. We discuss the relative weakness of these last characters at
      generic level, which lead us to assign the new species to Thalassaphorura instead
      of erecting a new genus. The diagnosis of Thalassaphorura is broadened
      accordingly. 

PMID- 24453542
TI  - Lumicella, a new genus of the tribe Empoascini (Hemiptera, Cicadellidae,
      Typhlocybinae) from China.
AB  - Lumicella rotundata gen. et sp. n. is described based on specimens from Fujian
      Province, China. Habitus photos and illustrations of male genitalia of this new
      species are provided. Differences between the new genus and closely related
      genera are discussed. 

PMID- 24453543
TI  - Are some prepupae and pupae of male mealybugs and root mealybugs (Hemiptera,
      Coccoidea, Pseudococcidae and Rhizoecidae) mobile?
AB  - It is hypothesised here that some mealybug (Pseudococcidae) and root mealybug
      (Rhizoecidae) prepupae and pupae are mobile. The prepupa and pupa of the mealybug
      Promyrmococcus dilli Williams and the prepupa of the root mealybug Ripersiella
      malschae (Williams) are described and illustrated and their probable mobility is
      discussed. It is also suggested that the prepupae and pupae of the mealybug
      Macrocepicoccus loranthi Morrison can move rapidly on the leaves when disturbed. 

PMID- 24453544
TI  - Pseudouroctonus peccatum, a new scorpion from the Spring Mountains near "Sin
      City," Nevada (Scorpiones, Vaejovidae).
AB  - A new scorpion species is described from the Spring Mountain Range near Las
      Vegas, Nevada. The new species appears to be geographically isolated from other
      closely related species of Uroctonites Williams & Savaryand Pseudouroctonus
      Stahnke. We tentatively place the new species in Pseudouroctonus and provide
      detailed descriptions and illustrations of type material. We compare the new
      species to 17 congeneric taxa, briefly discuss the taxonomic history of
      Pseudouroctonus, and provide DNA barcodes for two paratypes to assist ongoing
      research on the systematics of family Vaejovidae. 

PMID- 24453545
TI  - Integrative taxonomy and preliminary assessment of species limits in the
      Liolaemus walkeri complex (Squamata, Liolaemidae) with descriptions of three new
      species from Peru.
AB  - Species delimitation studies based on integrative taxonomic approaches have
      received considerable attention in the last few years, and have provided the
      strongest hypotheses of species boundaries. We used three lines of evidence
      (molecular, morphological, and niche envelopes) to test for species boundaries in
      Peruvian populations of the Liolaemus walkeri complex. Our results show that
      different lines of evidence and analyses are congruent in different combinations,
      for unambiguous delimitation of three lineages that were "hidden" within known
      species, and now deserve species status. Our phylogenetic analysis shows that L.
      walkeri, L. tacnae and the three new species are strongly separated from other
      species assigned to the alticolor-bibronii group. Few conventional morphological
      characters distinguish the new species from closely related taxa and this
      highlights the need to integrate other sources of data to erect strong hypothesis
      of species limits. A taxonomic key for known Peruvian species of the subgenus
      Lioalemus is provided. 

PMID- 24453546
TI  - A Tenebrionid beetle's dataset (Coleoptera, Tenebrionidae) from Peninsula Valdes
      (Chubut, Argentina).
AB  - The Natural Protected Area Peninsula Valdes, located in Northeastern Patagonia,
      is one of the largest conservation units of arid lands in Argentina. Although
      this area has been in the UNESCO World Heritage List since 1999, it has been
      continually exposed to sheep grazing and cattle farming for more than a century
      which have had a negative impact on the local environment. Our aim is to describe
      the first dataset of tenebrionid beetle species living in Peninsula Valdes and
      their relationship to sheep grazing. The dataset contains 118 records on 11
      species and 198 adult individuals collected. Beetles were collected using pitfall
      traps in the two major environmental units of Peninsula Valdes, taking into
      account grazing intensities over a three year time frame from 2005-2007. The Data
      quality was enhanced following the best practices suggested in the literature
      during the digitalization and geo-referencing processes. Moreover, identification
      of specimens and current accurate spelling of scientific names were reviewed.
      Finally, post-validation processes using DarwinTest software were applied.
      Specimens have been deposited at Entomological Collection of the Centro Nacional
      Patagonico (CENPAT-CONICET). The dataset is part of the database of this
      collection and has been published on the internet through GBIF Integrated
      Publishing Toolkit (IPT) (http://data.gbif.org/datasets/resource/14669/).
      Furthermore, it is the first dataset for tenebrionid beetles of arid Patagonia
      available in GBIF database, and it is the first one based on a previously
      designed and standardized sampling to assess the interaction between these
      beetles and grazing in the area. The main purposes of this dataset are to ensure
      accessibility to data associated with Tenebrionidae specimens from Peninsula
      Valdes (Chubut, Argentina), also to contribute to GBIF with primary data about
      Patagonian tenebrionids and finally, to promote the Entomological Collection of
      Centro Nacional Patagonico (CENPAT-CONICET) and its associated biodiversity data.
      For these reasons, we believe that this information will certainly be useful for
      future faunistic, ecological, conservational and biogeographical studies. 

PMID- 24453547
TI  - Editorial.

PMID- 24453548
TI  - The use of DNA barcoding to monitor the marine mammal biodiversity along the
      French Atlantic coast.
AB  - In the last ten years, 14 species of cetaceans and five species of pinnipeds
      stranded along the Atlantic coast of Brittany in the North West of France. All
      species included, an average of 150 animals strand each year in this area. Based
      on reports from the stranding network operating along this coast, the most common
      stranding events comprise six cetacean species (Delphinus delphis, Tursiops
      truncatus, Stenella coeruleoalba, Globicephala melas, Grampus griseus, Phocoena
      phocoena)and one pinniped species (Halichoerus grypus). Rare stranding events
      include deep-diving or exotic species, such as arctic seals. In this study, our
      aim was to determine the potential contribution of DNA barcoding to the
      monitoring of marine mammal biodiversity as performed by the stranding network.
      We sequenced more than 500 bp of the 5' end of the mitochondrial COI gene of 89
      animals of 15 different species (12 cetaceans, and three pinnipeds). Except for
      members of the Delphininae, all species were unambiguously discriminated on the
      basis of their COI sequences. We then applied DNA barcoding to identify some
      "undetermined" samples. With again the exception of the Delphininae, this was
      successful using the BOLD identification engine. For samples of the Delphininae,
      we sequenced a portion of the mitochondrial control region (MCR), and using a non
      metric multidimentional scaling plot and posterior probability calculations we
      were able to determine putatively each species. We then showed, in the case of
      the harbour porpoise, that COI polymorphisms, although being lower than MCR ones,
      could also be used to assess intraspecific variability. All these results show
      that the use of DNA barcoding in conjunction with a stranding network could
      clearly increase the accuracy of the monitoring of marine mammal biodiversity. 

PMID- 24453549
TI  - DNA barcoding of Dutch birds.
AB  - The mitochondrial cytochrome c oxidase subunit I (COI) can serve as a fast and
      accurate marker for the identification of animal species, and has been applied in
      a number of studies on birds. We here sequenced the COI gene for 387 individuals
      of 147 species of birds from the Netherlands, with 83 species being represented
      by > 2 sequences. The Netherlands occupies a small geographic area and 95% of all
      samples were collected within a 50 km radius from one another. The intraspecific
      divergences averaged 0.29% among this assemblage, but most values were lower; the
      interspecific divergences averaged 9.54%. In all, 95% of species were represented
      by a unique barcode, with 6 species of gulls and skua (Larus and Stercorarius)
      having at least one shared barcode. This is best explained by these species
      representing recent radiations with ongoing hybridization. In contrast, one
      species, the Lesser Whitethroat Sylvia curruca showed deep divergences, averaging
      5.76% and up to 8.68% between individuals. These possibly represent two distinct
      taxa, S. curruca and S. blythi, both clearly separated in a haplotype network
      analysis. Our study adds to a growing body of DNA barcodes that have become
      available for birds, and shows that a DNA barcoding approach enables to identify
      known Dutch bird species with a very high resolution. In addition some species
      were flagged up for further detailed taxonomic investigation, illustrating that
      even in ornithologically well-known areas such as the Netherlands, more is to be
      learned about the birds that are present. 

PMID- 24453551
TI  - The importance of biobanking in molecular taxonomy, with proposed definitions for
      vouchers in a molecular context.

PMID- 24453550
TI  - Applications of DNA barcoding to fish landings: authentication and diversity
      assessment.
AB  - DNA barcoding methodologies are being increasingly applied not only for
      scientific purposes but also for diverse real-life uses. Fisheries assessment is
      a potential niche for DNA barcoding, which serves for species authentication and
      may also be used for estimating within-population genetic diversity of exploited
      fish. Analysis of single-sequence barcodes has been proposed as a shortcut for
      measuring diversity in addition to the original purpose of species
      identification. Here we explore the relative utility of different mitochondrial
      sequences (12S rDNA, COI, cyt b, and D-Loop) for application as barcodes in
      fisheries sciences, using as case studies two marine and two freshwater catches
      of contrasting diversity levels. Ambiguous catch identification from COI and cyt
      b was observed. In some cases this could be attributed to duplicated names in
      databases, but in others it could be due to mitochondrial introgression between
      closely related species that may obscure species assignation from mtDNA. This
      last problem could be solved using a combination of mitochondrial and nuclear
      genes. We suggest to simultaneously analyze one conserved and one more
      polymorphic gene to identify species and assess diversity in fish catches. 

PMID- 24453552
TI  - The chloroplast DNA locus psbZ-trnfM as a potential barcode marker in Phoenix L.
      (Arecaceae).
AB  - The genus Phoenix (Arecaceae) comprises 14 species distributed from Cape Verde
      Islands to SE Asia. It includes the economically important species Phoenix
      dactylifera. The paucity of differential morphological and anatomical useful
      characters, and interspecific hybridization, make identification of Phoenix
      species difficult. In this context, the development of reliable DNA markers for
      species and hybrid identification would be of great utility. Previous studies
      identified a 12 bp polymorphic chloroplast minisatellite in the trnG (GCC)-trnfM
      (CAU) spacer, and showed its potential for species identification in Phoenix. In
      this work, in order to develop an efficient DNA barcode marker for Phoenix, a
      longer cpDNA region (700 bp) comprising the mentioned minisatellite, and located
      between the psbZ and trnfM (CAU) genes, was sequenced. One hundred and thirty-six
      individuals, representing all Phoenix species except P. andamanensis,were
      analysed. The minisatellite showed 2-7 repetitions of the 12 bp motif, with 1-3
      out of seven haplotypes per species. Phoenix reclinata and P. canariensis had
      species-specific haplotypes. Additional polymorphisms were found in the flanking
      regions of the minisatellite, including substitutions, indels and homopolymers.
      All this information allowed us to identify unambiguously eight out of the 13
      species, and overall 80% of the individuals sampled. Phoenix rupicola and P.
      theophrasti had the same haplotype, and so had P. atlantica, P. dactylifera, and
      P. sylvestris (the "date palm complex" sensu Pintaud et al. 2013). For these
      species, additional molecular markers will be required for their unambiguous
      identification. The psbZ-trnfM (CAU) region therefore could be considered as a
      good basis for the establishment of a DNA barcoding system in Phoenix, and is
      potentially useful for the identification of the female parent in Phoenix
      hybrids. 

PMID- 24453553
TI  - DNA barcodes and phylogenetic affinities of the terrestrial slugs Arion gilvus
      and A. ponsi (Gastropoda, Pulmonata, Arionidae).
AB  - The Iberian Peninsula is a region with a high endemicity of species of the
      terrestrial slug subgenus Mesarion. Many of these species have been described
      mainly on subtle differences in their proximal genitalia. It therefore remains to
      be investigated 1) whether these locally diverged taxa also represent different
      species under a phylogenetic species concept as has been shown for other Mesarion
      species outside the Iberian Peninsula, and 2) how these taxa are phylogenetically
      related. Here, we analysed DNA sequence data of two mitochondrial (COI and 16S)
      genes, and of the nuclear ITS1 region, to explore the phylogenetic affinities of
      two of these endemic taxa, viz. Arion gilvus Torres Minguez, 1925 and A. ponsi
      Quintana Cardona, 2007. We also evaluated the use of these DNA sequence data as
      DNA barcodes for both species. Our results showed that ITS did not allow to
      differentiate among most of the Mesarion molecular operational taxonomic units
      (MOTUs) / morphospecies in Mesarion. Yet, the overall mean p-distance among the
      Mesarion MOTUs / morphospecies for both mtDNA fragments (16.7% for COI, 13% for
      16S) was comparable to that between A. ponsi and its closest relative A. molinae
      (COI: 14.2%; 16S: 16.2%) and to that between A. gilvus and its closest relative
      A. urbiae (COI: 14.4%; 16S: 13.4%). Hence, with respect to mtDNA divergence, both
      A. ponsi and A. gilvus, behave as other Mesarion species or putative species
      level MOTUs and thus are confirmed as distinct 'species'. 

PMID- 24453554
TI  - Testing the performance of a fragment of the COI gene to identify western
      Palaearctic stag beetle species (Coleoptera, Lucanidae).
AB  - THE TAXONOMY OF STAG BEETLES (COLEOPTERA: Lucanidae) remains challenging, mainly
      due to the sexual dimorphism and the strong allometry in males. Such conjecture
      confounds taxonomic based conservation efforts that are urgently needed due to
      numerous threats to stag beetle biodiversity. Molecular tools could help solve
      the problem of identification of the different recognized taxa in the "Lucanus
      cervus complex" and in some related Palaearctic species. We investigated the
      potential use of a 670 bp region at the 3' end of the mitochondrial cytochrome c
      oxidase subunit I gene (COI) for barcoding purposes (different from the standard
      COI barcoding region). Well resolved species and subspecies were L. tetraodon, L.
      cervusakbesianus, L. c. laticornis, as well as the two eastern Asian outgroup
      taxa L. formosanus and L. hermani. Conversely, certain taxa could not be
      distinguished from each other based on K2P-distances and tree topologies: L. c.
      fabiani / L. (P.) barbarossa, L. c. judaicus / an unknown Lucanus species, L. c.
      cervus / L. c. turcicus / L. c. pentaphyllus / L. (P.) macrophyllus / L.
      ibericus. The relative roles of phenotypic plasticity, recurrent hybridisation
      and incomplete lineage sorting underlying taxonomic and phylogenetic discordances
      are discussed.

PMID- 24453555
TI  - Incorporating trnH-psbA to the core DNA barcodes improves significantly species
      discrimination within southern African Combretaceae.
AB  - Recent studies indicate that the discriminatory power of the core DNA barcodes
      (rbcLa + matK) for land plants may have been overestimated since their
      performance have been tested only on few closely related species. In this study
      we focused mainly on how the addition of complementary barcodes (nrITS and trnH
      psbA) to the core barcodes will affect the performance of the core barcodes in
      discriminating closely related species from family to section levels. In general,
      we found that the core barcodes performed poorly compared to the various
      combinations tested. Using multiple criteria, we finally advocated for the use of
      the core + trnH-psbA as potential DNA barcode for the family Combretaceae at
      least in southern Africa. Our results also indicate that the success of DNA
      barcoding in discriminating closely related species may be related to
      evolutionary and possibly the biogeographic histories of the taxonomic group
      tested. 

PMID- 24453557
TI  - DNA barcodes identify Central Asian Colias butterflies (Lepidoptera, Pieridae).
AB  - A majority of the known Colias species (Lepidoptera: Pieridae, Coliadinae) occur
      in the mountainous regions of Central-Asia, vast areas that are hard to access,
      rendering the knowledge of many species limited due to the lack of extensive
      sampling. Two gene regions, the mitochondrial COI 'barcode' region and the
      nuclear ribosomal protein RpS2 gene region were used for exploring the utility of
      these DNA markers for species identification. A comprehensive sampling of COI
      barcodes for Central Asian Colias butterflies showed that the barcodes
      facilitated identification of most of the included species. Phylogenetic
      reconstruction based on parsimony and Neighbour-Joining recovered most species as
      monophyletic entities. For the RpS2 gene region species-specific sequences were
      registered for some of the included Colias spp. Nevertheless, this gene region
      was not deemed useful as additional molecular 'barcode'. A parsimony analysis of
      the combined COI and RpS2 data did not support the current subgeneric
      classification based on morphological characteristics. 

PMID- 24453556
TI  - DNA barcoding and the differentiation between North American and West European
      Phormia regina (Diptera, Calliphoridae, Chrysomyinae).
AB  - Phormia regina (the black fly) is a common Holarctic blow fly species which
      serves as a primary indicator taxon to estimate minimal post mortem intervals. It
      is also a major research model in physiological and neurological studies on
      insect feeding. Previous studies have shown a sequence divergence of up to 4.3%
      in the mitochondrial COI gene between W European and N American P. regina
      populations. Here, we DNA barcoded P. regina specimens from six N American and 17
      W European populations and confirmed a mean sequence divergence of ca. 4% between
      the populations of the two continents, while sequence divergence within each
      continent was a ten-fold lower. Comparable mean mtDNA sequence divergences were
      observed for COII (3.7%) and cyt b (5.3%), but mean divergence was lower for 16S
      (0.4-0.6%). Intercontinental divergence at nuclear DNA was very low (<= 0.1% for
      both 28S and ITS2), and we did not detect any morphological differentiation
      between N American and W European specimens. Therefore, we consider the strong
      differentiation at COI, COII and cyt b as intraspecific mtDNA sequence divergence
      that should be taken into account when using P. regina in forensic casework or
      experimental research. 

PMID- 24453558
TI  - DNA barcoding as a complementary tool for conservation and valorisation of forest
      resources.
AB  - Since the pre-historic era, humans have been using forests as a food, drugs and
      handcraft reservoir. Today, the use of botanical raw material to produce
      pharmaceuticals, herbal remedies, teas, spirits, cosmetics, sweets, dietary
      supplements, special industrial compounds and crude materials constitute an
      important global resource in terms of healthcare and economy. In recent years,
      DNA barcoding has been suggested as a useful molecular technique to complement
      traditional taxonomic expertise for fast species identification and biodiversity
      inventories. In this study, in situ application of DNA barcodes was tested on a
      selected group of forest tree species with the aim of contributing to the
      identification, conservation and trade control of these valuable plant resources.
      The "core barcode" for land plants (rbcL, matK, and trnH-psbA) was tested on 68
      tree specimens (24 taxa). Universality of the method, ease of data retrieval and
      correct species assignment using sequence character states, presence of DNA
      barcoding gaps and GenBank discrimination assessment were evaluated. The markers
      showed different prospects of reliable applicability. RbcL and trnH-psbA
      displayed 100% amplification and sequencing success, while matK did not amplify
      in some plant groups. The majority of species had a single haplotype. The trnH
      psbA region showed the highest genetic variability, but in most cases the high
      intraspecific sequence divergence revealed the absence of a clear DNA barcoding
      gap. We also faced an important limitation because the taxonomic coverage of the
      public reference database is incomplete. Overall, species identification success
      was 66.7%. This work illustrates current limitations in the applicability of DNA
      barcoding to taxonomic forest surveys. These difficulties urge for an improvement
      of technical protocols and an increase of the number of sequences and taxa in
      public databases. 

PMID- 24453559
TI  - Efficacy of the core DNA barcodes in identifying processed and poorly conserved
      plant materials commonly used in South African traditional medicine.
AB  - Medicinal plants cover a broad range of taxa, which may be phylogenetically less
      related but morphologically very similar. Such morphological similarity between
      species may lead to misidentification and inappropriate use. Also the
      substitution of a medicinal plant by a cheaper alternative (e.g. other non
      medicinal plant species), either due to misidentification, or deliberately to
      cheat consumers, is an issue of growing concern. In this study, we used DNA
      barcoding to identify commonly used medicinal plants in South Africa. Using the
      core plant barcodes, matK and rbcLa, obtained from processed and poorly conserved
      materials sold at the muthi traditional medicine market, we tested efficacy of
      the barcodes in species discrimination. Based on genetic divergence, PCR
      amplification efficiency and BLAST algorithm, we revealed varied discriminatory
      potentials for the DNA barcodes. In general, the barcodes exhibited high
      discriminatory power, indicating their effectiveness in verifying the identity of
      the most common plant species traded in South African medicinal markets. BLAST
      algorithm successfully matched 61% of the queries against a reference database,
      suggesting that most of the information supplied by sellers at traditional
      medicinal markets in South Africa is correct. Our findings reinforce the utility
      of DNA barcoding technique in limiting false identification that can harm public
      health. 

PMID- 24453560
TI  - Using DNA barcoding to differentiate invasive Dreissena species (Mollusca,
      Bivalvia).
AB  - The zebra mussel (Dreissena polymorpha) and the quagga mussel (Dreissena
      rostriformis bugensis) are considered as the most competitive invaders in
      freshwaters of Europe and North America. Although shell characteristics exist to
      differentiate both species, phenotypic plasticity in the genus Dreissena does not
      always allow a clear identification. Therefore, the need to find an accurate
      identification method is essential. DNA barcoding has been proven to be an
      adequate procedure to discriminate species. The cytochrome c oxidase subunit I
      mitochondrial gene (COI) is considered as the standard barcode for animals. We
      tested the use of this gene as an efficient DNA barcode and found that it allow
      rapid and accurate identification of adult Dreissena individuals. 

PMID- 24453561
TI  - Which specimens from a museum collection will yield DNA barcodes? A time series
      study of spiders in alcohol.
AB  - We report initial results from an ongoing effort to build a library of DNA
      barcode sequences for Dutch spiders and investigate the utility of museum
      collections as a source of specimens for barcoding spiders. Source material for
      the library comes from a combination of specimens freshly collected in the field
      specifically for this project and museum specimens collected in the past. For the
      museum specimens, we focus on 31 species that have been frequently collected over
      the past several decades. A series of progressively older specimens representing
      these 31 species were selected for DNA barcoding. Based on the pattern of
      sequencing successes and failures, we find that smaller-bodied species expire
      before larger-bodied species as tissue sources for single-PCR standard DNA
      barcoding. Body size and age of oldest successful DNA barcode are significantly
      correlated after factoring out phylogenetic effects using independent contrasts
      analysis. We found some evidence that extracted DNA concentration is correlated
      with body size and inversely correlated with time since collection, but these
      relationships are neither strong nor consistent. DNA was extracted from all
      specimens using standard destructive techniques involving the removal and
      grinding of tissue. A subset of specimens was selected to evaluate nondestructive
      extraction. Nondestructive extractions significantly extended the DNA barcoding
      shelf life of museum specimens, especially small-bodied species, and yielded
      higher DNA concentrations compared to destructive extractions. All primary data
      are publically available through a Dryad archive and the Barcode of Life
      database. 

PMID- 24453562
TI  - Using DNA barcodes for assessing diversity in the family Hybotidae (Diptera,
      Empidoidea).
AB  - Empidoidea is one of the largest extant lineages of flies, but phylogenetic
      relationships among species of this group are poorly investigated and global
      diversity remains scarcely assessed. In this context, one of the most enigmatic
      empidoid families is Hybotidae. Within the framework of a pilot study, we
      barcoded 339 specimens of Old World hybotids belonging to 164 species and 22
      genera (plus two Empis as outgroups) and attempted to evaluate whether patterns
      of intra- and interspecific divergences match the current taxonomy. We used a
      large sampling of diverse Hybotidae. The material came from the Palaearctic
      (Belgium, France, Portugal and Russian Caucasus), the Afrotropic (Democratic
      Republic of the Congo) and the Oriental realms (Singapore and Thailand). Thereby,
      we optimized lab protocols for barcoding hybotids. Although DNA barcodes
      generally well distinguished recognized taxa, the study also revealed a number of
      unexpected phenomena: e.g., undescribed taxa found within morphologically very
      similar or identical specimens, especially when geographic distance was large;
      some morphologically distinct species showed no genetic divergence; or different
      pattern of intraspecific divergence between populations or closely related
      species. Using COI sequences and simple Neighbour-Joining tree reconstructions,
      the monophyly of many species- and genus-level taxa was well supported, but more
      inclusive taxonomical levels did not receive significant bootstrap support. We
      conclude that in hybotids DNA barcoding might be well used to identify species,
      when two main constraints are considered. First, incomplete barcoding libraries
      hinder efficient (correct) identification. Therefore, extra efforts are needed to
      increase the representation of hybotids in these databases. Second, the spatial
      scale of sampling has to be taken into account, and especially for widespread
      species or species complexes with unclear taxonomy, an integrative approach has
      to be used to clarify species boundaries and identities. 

PMID- 24453563
TI  - Half of the European fruit fly species barcoded (Diptera, Tephritidae); a
      feasibility test for molecular identification.
AB  - A FEASIBILITY TEST OF MOLECULAR IDENTIFICATION OF EUROPEAN FRUIT FLIES (DIPTERA:
      Tephritidae) based on COI barcode sequences has been executed. A dataset
      containing 555 sequences of 135 ingroup species from three subfamilies and 42
      genera and one single outgroup species has been analysed. 73.3% of all included
      species could be identified based on their COI barcode gene, based on similarity
      and distances. The low success rate is caused by singletons as well as some
      problematic groups: several species groups within the genus Terellia and
      especially the genus Urophora. With slightly more than 100 sequences - almost 20%
      of the total - this genus alone constitutes the larger part of the failure for
      molecular identification for this dataset. Deleting the singletons and Urophora
      results in a success-rate of 87.1% of all queries and 93.23% of the not discarded
      queries as correctly identified. Urophora is of special interest due to its
      economic importance as beneficial species for weed control, therefore it is
      desirable to have alternative markers for molecular identification. We
      demonstrate that the success of DNA barcoding for identification purposes
      strongly depends on the contents of the database used to BLAST against.
      Especially the necessity of including multiple specimens per species of
      geographically distinct populations and different ecologies for the understanding
      of the intra- versus interspecific variation is demonstrated. Furthermore
      thresholds and the distinction between true and false positives and negatives
      should not only be used to increase the reliability of the success of molecular
      identification but also to point out problematic groups, which should then be
      flagged in the reference database suggesting alternative methods for
      identification. 

PMID- 24453564
TI  - Utility of GenBank and the Barcode of Life Data Systems (BOLD) for the
      identification of forensically important Diptera from Belgium and France.
AB  - Fly larvae living on dead corpses can be used to estimate post-mortem intervals.
      The identification of these flies is decisive in forensic casework and can be
      facilitated by using DNA barcodes provided that a representative and
      comprehensive reference library of DNA barcodes is available. We constructed a
      local (Belgium and France) reference library of 85 sequences of the COI DNA
      barcode fragment (mitochondrial cytochrome c oxidase subunit I gene), from 16 fly
      species of forensic interest (Calliphoridae, Muscidae, Fanniidae). This library
      was then used to evaluate the ability of two public libraries (GenBank and the
      Barcode of Life Data Systems - BOLD) to identify specimens from Belgian and
      French forensic cases. The public libraries indeed allow a correct identification
      of most specimens. Yet, some of the identifications remain ambiguous and some
      forensically important fly species are not, or insufficiently, represented in the
      reference libraries. Several search options offered by GenBank and BOLD can be
      used to further improve the identifications obtained from both libraries using
      DNA barcodes. 

PMID- 24453565
TI  - Adhoc: an R package to calculate ad hoc distance thresholds for DNA barcoding
      identification.
AB  - Identification by DNA barcoding is more likely to be erroneous when it is based
      on a large distance between the query (the barcode sequence of the specimen to
      identify) and its best match in a reference barcode library. The number of such
      false positive identifications can be decreased by setting a distance threshold
      above which identification has to be rejected. To this end, we proposed recently
      to use an ad hoc distance threshold producing identifications with an estimated
      relative error probability that can be fixed by the user (e.g. 5%). Here we
      introduce two R functions that automate the calculation of ad hoc distance
      thresholds for reference libraries of DNA barcodes. The scripts of both
      functions, a user manual and an example file are available on the JEMU website
      (http://jemu.myspecies.info/computer-programs) as well as on the comprehensive R
      archive network (CRAN, http://cran.r-project.org). 

PMID- 24453566
TI  - Revisiting species delimitation within the genus Oxystele using DNA barcoding
      approach.
AB  - The genus Oxystele, a member of the highly diverse marine gastropod superfamily
      Trochoidea, is endemic to southern Africa. Members of the genus include some of
      the most abundant molluscs on southern African shores and are important
      components of littoral biodiversity in rocky intertidal habitats. Species
      delimitation within the genus is still controversial, especially regarding the
      complex O. impervia / O. variegata. Here, we assessed species boundaries within
      the genus using DNA barcoding and phylogenetic tree reconstruction. We analysed
      56 specimens using the mitochondrial gene COI. Our analysis delimits five
      molecular operational taxonomic units (MOTUs), and distinguishes O. impervia from
      O. variegata. However, we reveal important discrepancies between MOTUs and
      morphology-based species identification and discuss alternative hypotheses that
      can account for this. Finally, we indicate the need for future study that
      includes additional genes, and the combination of both morphology and genetic
      techniques (e.g. AFLP or microsatellites) to get deeper insight into species
      delimitation within the genus. 

PMID- 24453567
TI  - Problematic barcoding in flatworms: A case-study on monogeneans and rhabdocoels
      (Platyhelminthes).
AB  - Some taxonomic groups are less amenable to mitochondrial DNA barcoding than
      others. Due to the paucity of molecular information of understudied groups and
      the huge molecular diversity within flatworms, primer design has been hampered.
      Indeed, all attempts to develop universal flatworm-specific COI markers have
      failed so far. We demonstrate how high molecular variability and contamination
      problems limit the possibilities for barcoding using standard COI-based protocols
      in flatworms. As a consequence, molecular identification methods often rely on
      other widely applicable markers. In the case of Monogenea, a very diverse group
      of platyhelminth parasites, and Rhabdocoela, representing one-fourth of all free
      living flatworm taxa, this has led to a relatively high availability of nuclear
      ITS and 18S/28S rDNA sequences on GenBank. In a comparison of the effectiveness
      in species assignment we conclude that mitochondrial and nuclear ribosomal
      markers perform equally well. In case intraspecific information is needed, rDNA
      sequences can guide the selection of the appropriate (i.e. taxon-specific) COI
      primers if available. 

PMID- 24453569
TI  - Trogossitidae: A review of the beetle family, with a catalogue and keys.
AB  - THE FAMILY TROGOSSITIDAE (COLEOPTERA: Cleroidea) is reviewed to species level.
      Keys to its genera, tribes and subfamilies are presented for the first time. All
      known species and subspecies are listed, together with complete taxonomic
      references back to 1910, the date of issue of the last catalogue of
      Trogossitidae. Higher taxa reviews are accompanied by remarks on phylogeny,
      distribution and biology as well as a brief description of adults and larvae. All
      known fossil records of Trogossitidae are reviewed and discussed. The work
      includes maps of distribution, colour photographs of generic representatives,
      morphological illustrations, SEM photographs and phylogenetic trees.

PMID- 24453568
TI  - Reviewing population studies for forensic purposes: Dog mitochondrial DNA.
AB  - The identification of dog hair through mtDNA analysis has become increasingly
      important in the last 15 years, as it can provide associative evidence connecting
      victims and suspects. The evidential value of an mtDNA match between dog hair and
      its potential donor is determined by the random match probability of the
      haplotype. This probability is based on the haplotype's population frequency
      estimate. Consequently, implementing a population study representative of the
      population relevant to the forensic case is vital to the correct evaluation of
      the evidence. This paper reviews numerous published dog mtDNA studies and shows
      that many of these studies vary widely in sampling strategies and data quality.
      Therefore, several features influencing the representativeness of a population
      sample are discussed. Moreover, recommendations are provided on how to set up a
      dog mtDNA population study and how to decide whether or not to include published
      data. This review emphasizes the need for improved dog mtDNA population data for
      forensic purposes, including targeting the entire mitochondrial genome. In
      particular, the creation of a publicly available database of qualitative dog
      mtDNA population studies would improve the genetic analysis of dog traces in
      forensic casework. 

PMID- 24453570
TI  - Costs Associated with Intravenous Cancer Therapy Administration in Patients with
      Metastatic Soft Tissue Sarcoma in a US Population.
AB  - Background. The most common chemotherapies in metastatic soft tissue sarcoma
      (mSTS) require intravenous (IV) administration. This often requires patients to
      make multiple outpatient visits per chemotherapy cycle, possibly impeding
      patients' daily activities and increasing caregiver burden and medical costs.
      This study investigated costs associated with IV cancer therapy administration in
      mSTS from the payer perspective of the health care system. Patients and Methods.
      From the Experian Healthcare database, 1,228 mSTS patients were selected. Data
      were analyzed on outpatient visits during 2005-2012 involving IV cancer therapy
      administration. Costs were estimated on a per patient per visit (PPPV) and per
      patient per month (PPPM) basis. Results. The mean (median) cost of IV therapy was
      $2,427 ($1,532) PPPV and $5,468 ($4,310) PPPM, of which approximately 60% was IV
      drug costs. IV administration costs averaged $399 PPPV and $900 PPPM,
      representing 16.5% of total visit costs. Anthracycline and alkylating-agents
      based therapies had the highest PPPV and PPPM IV administration costs,
      respectively (mean $479 and $1,336, resp.). Patients with managed care insurance
      had the highest IV administration costs (mean $504 PPPV; $1,120 PPPM).
      Conclusions. IV administration costs constitute a considerable proportion of the
      total costs of receiving an IV cancer therapy to treat mSTS. 

PMID- 24453571
TI  - Non-thermal plasma-driven synthesis of Eu3+:Y2O3 nanosized phosphors.
AB  - The synthesis of nanosized phosphors by using the non-thermal plasma-driven
      method is presented. The method allows to control the average grain size of
      nanocrystals. The synthesis of Eu3+-doped Y2O3 nanocrystalline phosphors at water
      solution of nitrates is described. The average sizes of nanocrystals were
      controlled by sintering temperature. Their structure, morphology, and luminescent
      properties were investigated.

PMID- 24453572
TI  - Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture
      model.
AB  - OBJECTIVE: To investigate the role of ascorbic acid supplementation on bone
      healing after rat tibia fracture. METHODS: Thirty male Wistar rats were randomly
      divided into Vitamin C (Group A) and sham (Group B) groups (15 rats each). Group
      A received 200 mg intraperitoneally per kg per day of ascorbic acid and Group B
      was given saline 5 ml per kg per day intraperitoneally once a day. The animals
      were caged in pairs and allowed free access to tap water and a standard rodent
      chow ad libitum. Fractures were produced manually, they were not stabilized, and
      unprotected weight-bearing was allowed. At two, four, and six weeks post
      fracture, the rats in both groups were anesthetized and sacrificed by cervical
      dislocation. Callus tissue was dissected, prepared, and analyzed histologically.
      Histomorphological analysis was performed at six weeks post-fracture and the
      extent of fracture healing was determined using a five-point scale. RESULTS:
      There were no histological and histomorphological differences between drug
      treated animals and the sham in the three different stages studied. By six weeks
      post-fracture, the five animals of each group had a complete bone union.
      CONCLUSION: Under the studied conditions, intraperitoneal Vitamin C
      supplementation does not accelerate the fracture healing process after
      experimental tibia fracture in rats. LEVEL OF EVIDENCE: Level 2, individual study
      with experimental design.

PMID- 24453573
TI  - Morphological evaluation of eccentric sets guide-plates of dcp-l 4.5 mm.
AB  - OBJECTIVE: To carry out isolated and comparative evaluations of the measurements
      of the set eccentric guide plates used in 4.5mm surgical implants, and to
      determine the effect of these measurements on compression strength. METHODS: Four
      eccentric guides, four large dynamic compression plates (L-DCP) from four local
      manufacturers, and a Vonder((r)) 200 mm caliper brand were used. Five standard
      parameter measurements were created for the set eccentric guide-plate, which were
      identified as A to E. Four sets were made, using materials of the same factory,
      and identified as groups I to IV. The analyses were performed by measuring all
      the parameters from a ventral view of the plate, with the eccentric guide placed
      in the plate hole. RESULTS: Groups I and II showed the same values for all the
      parameters. All the groups showed the same measurements for E = 8.15 e B = 3.60.
      Group III: A = 8.10mm, C = 3.25mm, D = 1.25mm. Group IV: A = 7.00mm, C = 3.10mm,
      D = 0.30mm. Maximum compression force was (F Max.): Group I 80.58 N, Group. II: F
      Max. 81.63 N, Group. III: F Max. 36.32N, Group. IV: F Max. 37.52N. CONCLUSION:
      The measurements evaluated show a lack of standardization in the manufacture of
      orthopedic instruments and its effects on the values for compression strength.
      LEVEL OF EVIDENCE: Level III, analytical study.

PMID- 24453574
TI  - Photoelastic analisys in the lower region of vertebral body L4.
AB  - OBJECTIVE: To analyze the shear forces on the vertebral body L4 when submitted to
      a compression force by means of transmission photoelasticity. METHODS: Twelve
      photoelastic models were divided into three groups, with four models per group,
      according to the positioning of the sagittal section vertebrae L4-L5 (sections A,
      B and C). The simulation was performed using a 15N compression force, and the
      fringe orders were evaluated in the vertebral body L4 by the Tardy compensation
      method. RESULTS: Photoelastic analysis showed, in general, a homogeneous
      distribution in the vertebral bodies. The shear forces were higher in section C
      than B, and higher in B than A. CONCLUSION: The posterior area of L4, mainly in
      section C, showed higher shear concentrations, corresponding to a more
      susceptible area for bone fracture and spondylolisthesis. Economic and Decision
      Analyses - Development of an Economic or Decision Model. Level I.

PMID- 24453575
TI  - Anatomical description of the proximal third of the medial femoral circumflex
      artery. A cadaveric study.
AB  - OBJECTIVE: To describe, in a cadaver study, the anatomical arrangement of the
      proximal third medial femoral circumflex artery (MFCA). METHODS: We evaluated the
      anatomic arrangement of the proximal third of the MFCA through dissection in 12
      cadaver hips. After measuring their height in meters (M), several parameters were
      determined: angle of lateralization of MFCA (A), Depth MFCA in relation to the
      superomedial origin of the quadratus femoris muscle (P), and distance of MFCA
      from the superolateral insertion of the muscle quadratus femoris (D). RESULTS: IN
      THE COMPARISON OF MEAN PARAMETERS BETWEEN THE SEXES, IT WAS NOTED THAT: Male A =
      43.6 degrees, female A = 38.3 degrees. Male D = 6mm, female D = 9.5mm. Male P =
      20.8 mm, female P = 18.3mm. The average for parameters A and P were lower in
      females, but parameter D was higher in females. CONCLUSION: We should use, as the
      secure surface parameter for the proximal third of the MFCA, the superolateral
      insertion point of the quadratus femoris. The fact that the parameter D of MFCA
      is greater in females than in males. Disconnecting the quadratus femoris at its
      point of origin in the isquio may offer greater security to MFCA than doing it at
      the point of femoral insertion. Level of Evidence.

PMID- 24453576
TI  - Translation and Validation of the Knee Society Score - KSS for Brazilian
      Portuguese.
AB  - OBJECTIVE: To translate, culturally adapt and validate the "Knee Society
      Score"(KSS) for the Portuguese language and determine its measurement properties,
      reproducibility and validity. METHODS: We analyzed 70 patients of both sexes,
      aged between 55 and 85 years, in a cross-sectional clinical trial, with diagnosis
      of primary osteoarthritis ,undergoing total knee arthroplasty surgery. We
      assessed the patients with the English version of the KSS questionnaire and after
      30 minutes with the Portuguese version of the KSS questionnaire, done by a
      different evaluator. All the patients were assessed preoperatively, and again at
      three, and six months postoperatively. RESULTS: There was no statistical
      difference, using Cronbach's alpha index and the Bland-Altman graphical analysis,
      for the knees core during the preoperative period (p =1), and at three months (p
      =0.991) and six months postoperatively (p =0.985). There was no statistical
      difference for knee function score for all three periods (p =1.0). CONCLUSION:
      The Brazilian version of the Knee Society Score is easy to apply, as well
      providing as a valid and reliable instrument for measuring the knee score and
      function of Brazilian patients undergoing TKA. LEVEL OF EVIDENCE: Level I -
      Diagnostic Studies- Investigating a Diagnostic Test- Testing of previously
      developed diagnostic criteria on consecutive patients (with universally applied
      'gold' reference standard).

PMID- 24453577
TI  - Radiographic assessment of hips in patients with spinal cord injury.
AB  - OBJECTIVE: The spinal cord-injured patients begin to present a new configuration
      of forces on the joints. The hip joint is one of the most affected, because these
      patients generally use a wheelchair as a means of locomotion. Osteoarticular
      changes, such as heterotopic ossification, can be found in these patients, as
      evidenced by radiographic studies. This study aims to identify radiographic
      changes in hips of spinal cord-injured patients. METHODS: 15 patients (30 hips)
      were evaluated and followed up at the Laboratory of Biomechanical Rehabilitation
      of the Musculoskeletal System of HC-Unicamp, through the analysis of radiographs
      of the pelvis in anterior-posterior and Lowenstein lateral positions. RESULTS: Of
      the total hips, only seven (23%) had no evidence of articular damage. The
      prevalence of heterotopic ossification found (16.6%) was similar to the
      literature. CONCLUSION: The radiographic assessment of these patient's hips is
      justified by the prevalence of joint changes found. Level of Evidence II,
      Development of diagnostic criteria in consecutive patients (with universally
      applied reference "gold" standard).

PMID- 24453578
TI  - Reliability of the "American Knee Society Score" (AKSS).
AB  - OBJECTIVE: To analyze the reproducibility of the "American Knee Society Score"
      (AKSS) scale, and determine its measurement, in order to make it useful for the
      evaluation of patients with osteoarthritis or who have undergone total knee
      arthroplasty. METHODS: In the first interview, the AKSS was applied along with
      the SF-36 and WOMAC (examiner 1). After thirty minutes the same patients answered
      only the AKSS. After a two week break, a third additional interview with AKSS was
      applied (examiner 2). RESULTS: We selected 58 patients with a mean age of 67.4
      years. In the analysis of reproducibility, by ICC, there was strong inter
      examiner and intra-examiner correlation for two AKSS components. In the
      individual items analysis there was good correlation for "Pain", "Range of
      Motion", "Flexion contracture" and all items of the AKSS Function component.
      Validation through the Pearson coefficient showed good correlation between AKSS
      "Pain," WOMAC "pain" and SF-36 "Pain domain", and good correlation between the
      AKSS and SF-36 "Functional Capacity domain". CONCLUSION: The AKSS adapted to
      Brazilian culture is useful and reliable for the evaluation of individuals with
      osteoarthritis or those who have undergone TKA.

PMID- 24453579
TI  - Surgical treatment of intraarticular calcaneous fractures of sanders' types II
      and III. Systematic review.
AB  - OBJECTIVE: This paper aims to identify the most effective surgical technique for
      intraarticular calcaneal fractures of Sanders' types II and III. METHODS:
      Systematic review of comparative randomized clinical trials on surgical treatment
      of the intraarticular fractures of the calcaneus (Sanders types II and III) that
      used the questionnaire of the American Orthopaedic Foot and Ankle Society. The
      studies were identified and retrieved in the following databases - LILACS,
      MEDLINE/PubMed, Cochrane Library, SciELO, EMBASE, Science Direct, Scopus,
      Journals@Ovid, ISI Web of Knowledge, Evidence Based Medicine, besides consulting
      the references of studies accessed. The keywords used Boolean logic (AND and OR):
      "calcaneus fracture, calcaneous, calcaneal; surgical treatment, management; open
      reduction, minimally invasive, percutaneous reduction; internal fixation,
      external fixation. RESULTS: We identified only three randomized comparative
      trials. Each study compared a different technique (external fixation,
      percutaneous fixation with Kirchner wires and cannulated screws fixation) to the
      open reduction with internal fixation using plate and screws (considered the
      standard technique). CONCLUSION: Comparing the series, percutaneous fixation
      using Kirschner wires presented the best results, however, evidence is
      insufficient to assert superiority of this treatment in comparison with other
      surgical techniques.

PMID- 24453580
TI  - Musculoskeletal disorders in professional violinists and violists. Systematic
      review.
AB  - Due to the high physical and psychological demands of their work, musicians have
      a high risk of developing a range of health problems. The main causes of
      musculoskeletal disorders seen in instrumentalists are overuse, nerve compression
      and focal dystonia. The aim of this paper is to identify the musculoskeletal
      disorders that most frequently affect professional violinists and violists. 50
      articles were read, of which 24 were used. The PEDro scale was used to determine
      the quality of the articles. The definition of risk factors can help in the
      development of prevention programs. Playing a musical instrument involves a
      combination of actions, including rapid, repetitive and complicated movements of
      the hands and fingers. The chairs used offer no other option than to adapt to the
      demands of body posture. To achieve the necessary skills to become a musician of
      a high standard, many hours of training and perfection are required. The neck,
      shoulder and temporomandibular joints are the most commonly affected areas, due
      to prolonged flexion of the head and shoulder required to hold the violin. The
      elbow and fingers are also common sites of disorders. It is necessary to warn
      musicians of the initial symptoms, and how they can prevent the disorder from
      worsening. Level I Evidence (Centre for Evidence-Based Medicine, Oxford, UK). 

PMID- 24453581
TI  - The role of cytology in the diagnosis of musculoskeletal neoplasms: systematic
      review.
AB  - The authors systematically reviewed the literature of the last decade on the role
      of cytology in the evaluation of musculoskeletal neoplasms, and its diagnostic
      accuracy. A search was carried out on the databases PubMed, MEDLINE, LILACS and
      SciELO, selecting articles in which cytology was used in the diagnosis of
      musculoskeletal neoplasms. Limits were used for English, Spanish and Portuguese,
      and only articles published since 2000 were selected. 757 articles were
      retrieved, 24 of which were selected based on criteria of inclusion and
      exclusion. It was concluded that although promising in the assessment of
      musculoskeletal neoplasms, cytology obtained by fine needle aspiration is less
      accurate and reliable than histological evaluation of such lesions. 

PMID- 24453582
TI  - Epidemiology of fractures in patients from small towns in Ceara treated by the
      SUS.
AB  - OBJECTIVE: To scientifically prove the high number of patients with fractures
      coming from the small towns of the State of Ceara treated with surgery by the SUS
      (the Brazilian State healthcare system) in Fortaleza. METHODS: A transversal,
      prospective, descriptive study was carried out involving 1694 patients treated by
      the SUS in Fortaleza, from August 2006 to March 2007, in four public hospitals
      and three private hospitals. RESULTS: 38.78% of the patients came from small
      towns, and their ages ranged from 1 to 97 years old. The majority were single,
      male adults. The most common mechanism of injury was traffic accidents,
      accounting for 30.4% of all the cases. The forearm was the body segment most
      operated on, corresponding to 19%. CONCLUSIONS: These results suggest there is a
      need for preventive measures, such as public traffic safety awareness campaigns,
      in order to reduce accidents. We have also verified the importance of investments
      aimed at developing the Traumatology Emergency services in the small towns of
      Ceara. Level of evidence II, Transversal, Prospective Study (Lower quality
      prospective study).

PMID- 24453583
TI  - Comprehension and reproducibility of the Judet and Letournel classification.
AB  - OBJECTIVE: To evaluate the effectiveness of the method of radiographic
      interpretation of acetabular fractures, according to the classification of Judet
      and Letournel, used by a group of residents of Orthopedics at a university
      hospital. METHODS: We selected ten orthopedic residents, who were divided into
      two groups; one group received training in a methodology for the classification
      of acetabular fractures, which involves transposing the radiographic images to a
      graphic two-dimensional representation. We classified fifty cases of acetabular
      fracture on two separate occasions, and determined the intraobserver and
      interobserver agreement. RESULT: The success rate was 16.2% (10-26%) for the
      trained group and 22.8% (10-36%) for the untrained group. The mean kappa
      coefficients for interobserver and intraobserver agreement in the trained group
      were 0.08 and 0.12, respectively, and for the untrained group, 0.14 and 0.29.
      CONCLUSION: Training in the method of radiographic interpretation of acetabular
      fractures was not effective for assisting in the classification of acetabular
      fractures. Level of evidence I, Testing of previously developed diagnostic
      criteria on consecutive patients (with universally applied reference "gold"
      standard).

PMID- 24453584
TI  - Tomographic analysis of anatomical parameters of the axis in children.
AB  - OBJECTIVE: To carry out an anatomical study of the axis with the use of computed
      tomography (CT) in children aged from two to ten years, measuring the lamina
      angle, lamina and pedicle length and thickness, and lateral mass length. METHODS:
      Sixty-four CTs were studied from patients aged 24 to 120 months old, of both
      sexes and without any cervical anomaly. The measurements obtained were correlated
      with the data on age and sex of the patients. Statistical analysis was performed
      using the Students "t" tests. RESULTS: We found that within the age range 24-48
      months, 5.5% of the lamina and 8.3% of the pedicles had thicknesses of less than
      3.5mm, which is the minimum thickness needed for insertion of the screw. Between
      49 and 120 months, there were no lamina thicknesses of less than 3.5mm, and 1.2%
      of the pedicle thicknesses were less than 3.5mm values. Neither of the age groups
      had any lamina and pedicle lengths of less than 12mm, or lateral mass lengths
      greater than 12mm. CONCLUSION: The analysis of the data obtained demonstrates
      that most of the time, is possible to use a 3.5mm pedicle screw in the laminas
      and pedicles of the axis in children. LEVEL OF EVIDENCE: II, Development of
      diagnostic criteria in consecutive patients.

PMID- 24453585
TI  - Radiographic anatomy of the proximal femur: correlation with the occurrence of
      fractures.
AB  - OBJECTIVE: To evaluate the correlation between radiographic parameters of the
      proximal femur anatomy and fractures. METHODS: Three hundred and five digital x
      rays of the pelvis were analyzed in the anteroposterior view. Of these x-rays,
      twenty-seven showed femoral neck or transtrochanteric fractures. The anatomical
      parameters analyzed were: femoral neck width (FNW), femoral neck length (FNL),
      femoral axis length (FAL), cervicodiaphyseal angle (CDA), acetabular tear-drop
      distance (ATD) and great trochanter-pubic symphysis distance (GTPSD). The
      analysis was performed by comparing the results of the x-rays with and without
      proximal femoral fracture, to establish a correlation between them. RESULTS: No
      differences were found between the anatomical parameters of the groups with and
      without proximal femoral fracture. CONCLUSION: There was no association between
      anatomical changes in the proximal femur and greater susceptibility to fractures.
      Level of evidence IV, Cross-sectional Study.

PMID- 24453586
TI  - Traumatic spondylolisthesis of the axis: epidemiology, management and outcome.
AB  - OBJECTIVE: To evaluate cases of traumatic spondylolisthesis of the axis and
      describe them in relation to epidemiology, classification, neurological deficit,
      healing time and treatment method. METHOD: A retrospective analysis of the
      medical records of patients treated between 2002 and 2010 at IOT-FMUSP. INCLUSION
      CRITERIA: pars interarticularis fracture of C2. RESULTS: 68% were male patients,
      with a mean age of 39.1 years. We used the classification by Effendi, modified by
      Levine-Edwards. Type I fractures were observed in five patients (31.2%) and type
      II in eight patients (50%). Only three patients (18%) had type IIa fracture.
      There were no cases of type III. Mechanism: Eight car accidents and four falls.
      Other mechanisms: being run over, and diving accidents. Treatment with halo
      traction was used in eleven patients, using minerva cast and halo-cast. Healing
      time: 3.6 months. Follow-up time: 9.6 months. DISCUSSION: In general, hangman
      fracture has a good prognosis, which is confirmed by our results. There was no
      need for surgery in any of the cases. The incidence of neurological deficit is
      low. No patient had unstable fracture (type III). CONCLUSION: This paper suggests
      that traumatic spondylolisthesis of the axis continues to be an injury that is
      successfully treated by conservative treatment in most cases. Level of Evidence 
      IV, Case series.

PMID- 24453587
TI  - Translation and cross-cultural adaptation of the International Hip Outcome Tool
      (iHOT) into Portuguese.
AB  - OBJECTIVE: iHOT12/33 is an outcome tool designed for young patients with hip
      problems. The objective of this study is to translate and establish a cross
      cultural adaptation of this questionnaire to Portuguese. METHOD: The Guillemin
      guidelines were followed for the translation and cross-cultural adaptation
      consisting on: translation, back-translation, prefinal version, administration of
      the Questionnaire, and editing of the final version. RESULTS: The prefinal
      version was applied to 30 young patients with hip problems. Some difficulties in
      understanding some of the words and expressions were noted, and these were
      replaced with simpler ones, achieving the patient's full acceptability in the
      final version of the Questionnaire. CONCLUSION: The creation of the Brazilian
      version of the International Hip Outocome Tool (iHOT) 12/33 enables this
      questionnaire to be used in the evaluation of patients with hip problems in
      Brazil, and was clearly understood, with good acceptance by the patients tested.
      Level of evidence II - Development of diagnostic criteria on consecutive patients
      (with universally applied reference "gold" standard).

PMID- 24453588
TI  - High voltage pulsed current stimulation of the sciatic nerve in rats: analysis by
      the SFI.
AB  - OBJECTIVE: To analyze the efficiency of high voltage pulsed current (HVPC) with
      early application in three different sites, in the regeneration of the sciatic
      nerve in rats submitted to crush injury, the sciatic functional index (SFI) was
      used to assess the functional recovery. METHODS: After crushing of the nerve, 57
      animals were submitted to cathodal HVPC at frequency of 50Hz and voltage of 100V,
      20 minutes per day, 5 days per week. The rats were divided into five groups:
      control group; ganglion group; ganglion + muscle group; muscle group; and sham
      group. The SFI was determined weekly for seven weeks, from the preoperative
      period to the 6(th) postoperative week. RESULTS: Compared with the control group,
      the results showed a significantly better performance of group 2 for the first 3
      weeks; group 3 showed significantly better performance in the third week; and
      group 4 showed a significantly negative performance during the 4(th) and 6(th)
      weeks. CONCLUSION: Early application of HVPC had a positive effect in the
      treatment of the spinal cord region and the sciatic nerve root ganglion with a
      dispersive electrode on the contralateral lumbar region or on the gastrocnemius.
      However, HVPC had a negative effect in the treatment with an active electrode on
      the gastrocnemius and a dispersive electrode on the contralateral thigh. Level of
      evidence II, Prospective comparative study.

PMID- 24453589
TI  - Action of therapeutic laser and ultrasound in peripheral nerve regeneration.
AB  - OBJECTIVE: To assess the efficacy of early therapeutic laser and ultrasound in
      the regeneration process of an injury in rats. METHODS: We used 24 rats. Eighteen
      underwent surgery for sciatic nerve compression by a hemostat above the popliteal
      fossa. The animals were divided into three groups of six animals each. Normal
      control group. GI: Injured control without therapeutic intervention. GII: laser
      ArGaAl therapeutic intervention. GIII: therapeutic intervention of Pulsed
      Ultrasound. We begin therapeutic interventions 24 hours after injury, with daily
      applications for a period of fourteen consecutive days. RESULTS: IN ASSESSING THE
      GIRTH OF THE MUSCLES OF THE RIGHT THEY, THE FOLLOWING AVERAGE DECREASE (IN MM)
      FOR EACH GI: 0.45, GII: 0.42, GIII: 0.40 In relation to travel time, both GII and
      GIII presented significant difference when compared to GI. In the final
      evaluation of the IFC, GII excelled in the GIII. As for the healing observed, a
      major great improvement was observed in GII and GIII. CONCLUSION: The results
      showed that nerve recovery was higher with the laser application. Level of
      evidence II, Therapeutic Studies - Investigation of the results of treatment.

PMID- 24453590
TI  - Limb replantation after avulsion injuries: techniques and tactics for success.
AB  - OBJECTIVES: Retrospective evaluation of cases of limb replantation after avulsion
      injuries. Evaluation of the techniques and tactics used, that contributed to
      success and good functional results. METHODS: Forty-three patients' records were
      assessed. All the cases had been submitted to limb replantation after avulsion
      injuries. RESULTS: The majority of the cases were young men. The most common
      injury was to the thumbs. The surgical techniques and tactics used were: nerve
      grafting, vein grafting, transposition of the digital vessels, limb shortening,
      and heterotopic replantation. The most commonly used technique was vein graft.
      The limb survival rate was high (93%), as was patient satisfaction. CONCLUSION:
      Replantation after avulsion injury depends on the correct diagnosis of the limb
      viability and the use of appropriate surgical techniques and tactics for each
      case. The experience of the team of surgeons and a good hospital structure are
      essential for good results. There are few articles in medical literature about
      the indications, techniques and results of limb replantation after avulsion
      injuries. We believe that this retrospective evaluation can bring new information
      and contributions to the correct management of this highly complex situation.
      Level of evidence IV, Case Series.

PMID- 24453591
TI  - Global research coaching in orthopedic surgery: seeding for an international
      network.
AB  - Despite the importance of delivering evidence-based health care, orthopedic
      surgeons have directed fewer efforts towards the generation of such evidence.
      Even when present, published evidence lacks methodological rigor and is known to
      be inaccurate. One of the main reasons for the lack of generation of quality
      evidence, and the low involvement in research among orthopedic surgeons, is the
      lack of structured research coaching environments where they can learn concepts
      and hone their research skills. There is a palpable need for a pragmatic and
      outcome-oriented approach that can equip orthopedic surgeons with effective ways
      of communicating their research in writing. We describe a pragmatic research
      coaching program, designed and developed by the Research on Research group, which
      aims to build a global network of orthopedic researchers trained in streamlined
      and standardized research methods. We also provide a brief overview of the course
      principles and tools, and the platforms used in this program. 

PMID- 24453592
TI  - Effects of kinesiotherapy in ischemic lesion and reperfusion in rats.
AB  - OBJECTIVE: To investigate the effect of kinesiotherapy on the functionality of
      the pelvic limb of rats after ischemic and reperfusion injury. METHODS: 10 rats
      were divided into two groups, GI (control) and GII (kinesiotherapy). All the
      animals underwent ischemia for a period of three hours, followed by tissue
      reperfusion. In Group GII, non-resistive systemic kinesiotherapy was performed
      (swimming) in three weekly sessions of 50 minutes, over a period of four weeks,
      while the GI animals remained at rest. Functional analysis of motor behavior was
      evaluated weekly. The animals were then sacrificed, and the soleus and
      gastrocnemius muscles and the sciatic nerve removed for histopathological
      analysis. RESULTS: There was a significant recovery of motor behavior with
      kinesiotherapeutic treatment during the four weeks of treatment. However, the
      histological examination of the tissues showed no morphological changes of cell
      injury and repair. CONCLUSION: It was not possible to affirm that the exercise
      was effective in cell repair, because neither of the groups (control and
      experimental) showed any histological difference. On the other hand, systemic
      kinesiotherapy showed a beneficial effect on functional rehabilitation after
      ischemia and reperfusion. Level of evidence III, Case-Control Study .

PMID- 24453593
TI  - Development of an experimental model of infected bone void in the ulna of
      rabbits.
AB  - OBJECTIVE: Develop a model that allowed the study of bone regeneration in
      infection conditions. METHOD: A 15 mm defect was surgically created in the rabbit
      ulna and inoculated with 5x10(8) colony-forming units (CFU) of S. aureus.
      Surgical debridement was performed two weeks after and systemic gentamicin was
      administered for four weeks. Animals were followed up to 12 weeks to evaluate
      infection control and bone regeneration. RESULT: Bone regeneration was inferior
      to 25% of the defect in radiological and histological analysis. CONCLUSION:
      Infected bone defect of 15 mm in the rabbit ulna was unable to achieve full
      regeneration without further treatment. Level of Evidence V, Experimental Study.

PMID- 24453594
TI  - Analysis of the reliability and reproducibility of goniometry compared to hand
      photogrammetry.
AB  - OBJECTIVE: To evaluate the intra- and inter-examiner reliability and
      reproducibility of goniometry in relation to photogrammetry of hand, comparing
      the angles of thumb abduction, PIP joint flexion of the II finger and MCP joint
      flexion of the V finger. METHODS: The study included 30 volunteers, who were
      divided into three groups: one group of 10 physiotherapy students, one group of
      10 physiotherapists, and a third group of 10 therapists of the hand. Each
      examiner performed the measurements on the same hand mold, using the goniometer
      followed by two photogrammetry software programs; CorelDraw((r)) and
      ALCimagem((r)). RESULTS: The results revealed that the groups and the methods
      proposed presented inter-examiner reliability, generally rated as excellent (ICC
      0.998 I.C. 95% 0.995 - 0.999). In the intra-examiner evaluation, an excellent
      level of reliability was found between the three groups. In the comparison
      between groups for each angle and each method, no significant differences were
      found between the groups for most of the measurements. CONCLUSION: Goniometry and
      photogrammetry are reliable and reproducible methods for evaluating measurements
      of the hand. However, due to the lack of similar references, detailed studies are
      needed to define the normal parameters between the methods in the joints of the
      hand. Level of Evidence II, Diagnostic Study.

PMID- 24453595
TI  - Biomechanical changes in gait of subjects with medial knee osteoarthritis.
AB  - OBJECTIVE: Demonstrate the presence and magnitude of biomechanical variables
      during gait in patients with medial knee osteoarthritis (OA) and the relationship
      with the knee loading. METHODS: Gait of 21 subjects diagnosed with medial knee OA
      was evaluated and compared to the control group. RESULTS: THE GROUP WITH OA
      SHOWED: Lower gait speed (0.8 +/- 0.1 vs. 1.1 +/- 0.1m/s), higher peak early (2.6
      +/- 1.2 vs. 0.3 +/- 1.4 Nm/Kg) and late peak of the adduction moment (1.8 +/- 0.7
      vs. 0.9 +/- 0.2 Nm/Kg), higher peak flexor moment (1.6 +/- 0.9 vs. 0.6 +/- 0.4
      Nm/Kg), high dynamic peak varus (11.5o +/- 8.3 vs. 3o +/- 3.9), higher peak
      flexion (15.6o +/- 8 vs. 9.3o to +/- 4.1), with a flexion tendency (5.5o +/- 8.5)
      in the stance phase, smaller peak of flexion (58.7o +/- 13.3 vs. 67.5o +/- 4.8)
      in the balance phase and higher peaks of external rotation (25.5o +/- 12.7 vs.
      0.5o +/- 22.4). CONCLUSION: Patients with medial knee OA show changes in gait
      with increased external rotation, speed reduction, increased flexor moment and
      flexion in the stance phase, insufficient for reduction of the load. Level of
      Evidence III, Case Control Study.

PMID- 24453596
TI  - Study of the anatomy of the tibial nerve and its branches in the distal medial
      leg.
AB  - OBJECTIVE: Determine, through dissection in fresh cadavers, the topographic
      anatomy of the tibial nerve and its branches at the ankle, in relation to the
      tarsal tunnel. METHODS: Bilateral dissections were performed on 26 fresh cadavers
      and the locations of the tibial nerve bifurcation and its branches were measured
      in millimeters. For the calcaneal branches, the amount and their respective
      nerves of origin were also analyzed. RESULTS: The tibial nerve bifurcation
      occurred under the tunnel in 88% of the cases and proximally in 12%. As for the
      calcaneal branches, the medial presented with one (58%), two (34%) and three (8%)
      branches, with the most common source occurring in the tibial nerve (90%) and the
      lower with a single branch per leg and lateral plantar nerve as the most common
      origin (70%). Level of Evidence, V Expert opinion .

PMID- 24453597
TI  - Study of tibial nerve regeneration in Wistar rats in primary neurorrhaphy with
      and without gap, wrapped in vein segments.
AB  - OBJECTIVE: This study compared nerve regeneration in Wistar rats, using epineural
      neurorrhaphy with a gap of 1.0 mm and without a gap, both wrapped with jugular
      vein tubes. Motor neurons in the spinal cord between L3 and S1 were used for the
      count, marked by exposure of the tibial nerve to Fluoro-Gold (FG). METHOD: The
      tibial nerves on both sides were cut and sutured, with a gap on one side and no
      gap in the other. The sutures were wrapped with a jugular vein. Four months after
      surgery the tibial nerves were exposed to Fluoro-Gold and the motor neuron count
      performed in the spinal cord. RESULTS: The results were statistically analyzed by
      the paired Wilcoxon test. There was a statistical difference between the groups
      with and without gap in relation to the motor neuron count (p=0.013). CONCLUSION:
      The epineural neurorraphy without gap wrapped with jugular vein showed better
      results for nerve regeneration than the same procedure with gap. LEVEL OF
      EVIDENCE: Experimental Study .

PMID- 24453598
TI  - Fractures of the neck of the talus: evaluation of reproducibility of Hawkins'
      classification.
AB  - OBJECTIVE: To evaluate the intraobserver and interobserver reproducibility of
      Hawkins' classification for fractures of the neck of the talus. METHODS: 20
      random cases of fracture of the talus were selected, to be defined according to
      the classification of types by eight orthopedic surgeons, 13 orthopedic residents
      and 15 radiology residents. RESULTS: Using the statistical test of Landis and
      Koch, measurements of 0.627 and 0.668 were obtained in the first and second
      evaluations, respectively. These values define a satisfactory agreement for
      Hawkins' classification. CONCLUSION: We conclude that this classification is
      reproducible between observers, with better values for the more experienced
      observers. Level of Evidence I, Study Diagnostic - Investigating a diagnostic
      test.

PMID- 24453599
TI  - Quadriceps strengthening exercises are effective in improving pain, function and
      quality of life in patients with osteoarthritis of the knee.
AB  - OBJECTIVE: The purpose of this research was to verify the effectiveness of an
      eight-week quadriceps strengthening program on pain, function and quality of life
      of patients with knee osteoarthritis. METHODS: A HUNDRED PATIENTS WERE RANDOMIZED
      INTO TWO GROUPS: 1- Exercise Group (ExG) and 2- Orientation Group. The Timed Up
      and Go (TUG) test, the Numerical Rating Scale (NRS) and the Short Form-36 were
      used for the assessment. RESULTS: Eighty-one patients completed the survey.
      According to the intention to treat (ITT) analysis, there was statistically
      significant difference in ExG compared to OG in all the variables assessed.
      CONCLUSION: The program quadriceps strengthening exercises applied in this
      randomized clinical trial was effective in improving pain, function and quality
      of life of patients with knee osteoarthritis. Level of Evidence I, Randomized
      Clinical Trial.

PMID- 24453600
TI  - Correlation between the clinic and the index of cervical myelopathy Torg.
AB  - OBJECTIVE: Cervical myelopathy is a spinal cord dysfunction related to
      degeneration typical of aging. Its primary pathology is related to ischemia and
      spinal cord compression. Patients with myelopathy present many clinical problems;
      more severe cases may lead to quadriplegia if not treated in a timely manner.
      Because the primary pathology of this disease is caused by compression, thus
      generating spinal cord ischemia, we believed there must be a correlation between
      the degree of compression and the clinical assessment of patients with cervical
      myelopathy, but we did not find any study in the literature that made this
      correlation. Because there is doubt the literature we aimed, in our study, to
      analyze the correlation between the degree of clinical impairment of patients
      with cervical myelopathy and the Torg index. METHODS: A prospective, descriptive
      study, evaluating 46 patients, in which radiographic measurements of the Torg
      index were performed, with clinical analysis through the Nurick and JOA scale.
      RESULTS: Of the 46 study patients included in the study, 100% presented a Torg
      score <0.8. The decrease in Torg values was directly proportional to clinical
      worsening on the Nurick and JOA scale. CONCLUSIONS: The degree of clinical
      impairment in patients with cervical myelopathy is directly related to the degree
      of spinal canal stenosis. Level of Evidence I, Prognostic Studies - Investigating
      the effect of the characteristics of a patient on the outcome of the disease.

PMID- 24453601
TI  - Influence of cortical bone thickness on the ultrasound velocity.
AB  - OBJECTIVE: An experimental in vitro study was carried out to evaluate the
      influence of cortical bone thickness on ultrasound propagation velocity. METHODS:
      Sixty bone plates were used, made from bovine femurs, with thickness ranging from
      1 to 6 mm (10 of each). The ultrasound velocity measurements were performed using
      a device specially designed for this purpose, in an underwater acoustic tank and
      with direct contact using contact gel. The transducers were positioned in two
      ways: on opposite sides, with the bone between them, for the transverse
      measurement; and parallel to each other, on the same side of the bone plates, for
      the axial measurements. RESULTS: In the axial transmission mode, the ultrasound
      velocity speed increased with cortical bone thickness, regardless of the distance
      between the transducers, up to a thickness of 5 mm, then remained constant
      thereafter. There were no changes in velocity when the transverse measures were
      made. CONCLUSION: Ultrasound velocity increased with cortical bone thickness in
      the axial transmission mode, until the thickness surpasses the wavelength, after
      which point it remained constant. LEVEL OF EVIDENCE: Experimental Study.

PMID- 24453602
TI  - Radiographic evaluation in epiphysiolysis: possible predictors of bilaterality?
AB  - OBJECTIVE: To identify anatomical changes and skeletal maturity through
      radiographic analysis, allowing more accuracy for indication of surgical
      management of non-slipped hips in patients with epiphysiolisys. METHOD: A
      retrospective study of the radiographs of 61 patients followed until the end of
      skeletal growth, assigned to two groups: 37 patients with unilateral
      epiphysiolysis, and 24 patients with contralateral epiphysiolysis diagnosed
      during follow-up. The skeletal maturity was evaluated using pelvis radiographs
      (Oxford method) and compared between the groups for patients of the same gender.
      In addition, the Southwick angle (in anteroposterior and in Lauenstein view),
      physeal sloping angle and physeal posterior sloping angle were compared as well.
      RESULTS: Skeletal maturity showed a statistically significant difference between
      the two groups for both genders. It was observed that the lateral view of the
      Southwick angle is mathematically equal to the physeal posterior sloping angle,
      and were the only ones to show relevant differences between the groups.
      CONCLUSION: The Oxford method and the Southwick angle in Lauenstein view can be
      utilized as parameters to help the physician to better indicate the prophylactic
      surgical treatment of the contralateral hip, in patients with slipped capital
      femoral epiphysis (SCFE). Level of Evidence III, Diagnostic Study.

PMID- 24453603
TI  - Tomographic analysis for C2 screw placement in rheumatoid arthritis patients.
AB  - OBJECTIVE: A morphological analysis of the bone structure of C2 in patients with
      rheumatoid arthritis in order to enhance the security of the stabilization
      procedures for this vertebra. METHODS: We retrospectively analyzed 20 CT scans of
      the cervical spine performed in patients with rheumatoid arthritis; the following
      parameters were measured: spinolaminar angle, thickness and length of C2 lamina.
      RESULTS: THE MEAN VALUES ARE: 5.92mm and 5.87mm for thickness of right and left
      laminae retrospectively, 27.75mm for right lamina length and 27.94mm for left
      lamina length, and 44.7o for spinolaminar angle. CONCLUSION: The values obtained
      are consistent with studies in normal subjects published by other groups, with no
      apparent need for change in the screw placement technique. Level of Evidence IV,
      Case Series.

PMID- 24453604
TI  - Comparison of static postural balance between healthy subjects and those with low
      back pain.
AB  - OBJECTIVE: To compare the static postural balance between women suffering from
      chronic low back pain and healthy subjects, by moving the center of pressure.
      METHODS: The study included 15 women with low back pain (LBP group) and 15
      healthy women (healthy group). They were instructed to remain in standing on the
      force platform for 30 seconds. We analyzed the area and the speed of displacement
      of center of pressure of both groups. Data analysis was performed using the
      Student's t-test, with significance of 5%. RESULTS: Individuals with chronic low
      back pain showed a larger area of displacement of the center of pressure relative
      to the healthy ones but there was no significant difference in the speed of
      displacement of the center of pressure. CONCLUSION: Individuals with chronic low
      back pain had alterations in static balance with respect to healthy ones. Level
      of Evidence III, Prognostic Studies.

PMID- 24453606
TI  - Muscle mechanical properties of adult and older rats submitted to exercise after
      immobilization.
AB  - OBJECTIVES: To describe the effects of immobilization, free remobilization and
      remobilization by physical exercise about mechanical properties of skeletal
      muscle of rats of two age groups. METHODS: 56 Wistar rats divided into two groups
      according to age, an adult group (five months) and an older group (15 months).
      These groups were subdivided in: control, immobilized, free remobilized and
      remobilized by physical exercise. The pelvic limb of rats was immobilized for
      seven days. The exercise protocol consisted of five swimming sessions, once per
      day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile
      tests, and evaluated the properties: load at the maximum limit, stretching at the
      maximum limit and stiffness. RESULTS: The immobilization reduced the values of
      load at the maximum limit and the remobilization protocols were not sufficient to
      restore control levels in adult group and older rats. The stretching at the
      maximum limit differs only in the older group. CONCLUSIONS: The immobilization
      reduces the muscle's ability to bear loads and exercise protocol tends to restore
      the default at control values in adult and older rats. The age factor only
      interfered in the stretching at the maximum limit, inducing a reduction of this
      property in the post-immobilization. Level of Evidence II, Investigating the
      Results of Treatment.

PMID- 24453605
TI  - Evaluation of the reliability of the modified Merle d'Aubigne and Postel Method.
AB  - OBJECTIVE: To assess the inter-evaluator reproducibility of the Modified Merle
      d'Aubigne and Postel Method. METHOD: Forty-five patients took part in the study,
      with a mean age of 57.93 (+/-13.35) who underwent total hip arthroplasty. All
      were evaluated by three researchers, who received training to standardize their
      criteria. The evaluation was held by the Modified Merle d'Aubigne and Postel
      Method (association of prefixes A, B and C) the same day at random, and the
      researchers did not report to one another throughout the evaluations. For
      mobility assessment, passive hip movements were performed and measured with the
      universal goniometer. The statistical analysis was carried out by the Cronbach
      Test (p<=0.05 and 0.7<= alpha<1.0). RESULTS: The statistical analysis showed
      significantly high inter-evaluators reliability for the items: prefix (p<0.001;
      alpha = 0.961), pain (p<0.001; alpha= 0.892), gait (p<0.001; alpha= 0.898),
      mobility (p<0.001; alpha=0.810) and total score (p<0.001; alpha=0.917).
      CONCLUSION: There was high significance and reliability among the three
      evaluators for all items of the Modified Merle d'Aubigne and Postel Method,
      suggesting that this method is reliable, provided its items are parameterized and
      previous training of evaluators is carried out. Level of Evidence II, Diagnostic
      Study.

PMID- 24453607
TI  - Results of surgical treatment of nonunion of humeral shaft fracture with dynamic
      compression plate and cancellous bone grafting.
AB  - OBJECTIVE: We evaluated the treatment of nonunion of humeral shaft fracture with
      dynamic compression plate from January 2002 to December 2009. METHODS: Twenty-two
      patients were treated over the study period. Trauma was the predominant cause of
      injury in 86.4% of the patients. RESULTS: Nonunion was atrophic in 81.8% and
      hypertrophic in 18.2% of the individuals. There was a primary injury of the
      radial nerve in 27.3% of the patients. All the participants had closed fracture
      at presentation, and 81.2% had received previous treatment from traditional bone
      setters and 18.8% had failure of the conservative cast management. The average
      time to healing was 16 weeks. Previous treatment from traditional bone setters
      significantly affected the time to fracture healing (p<0.05). All fractures had
      successful union. CONCLUSION: It was concluded that dynamic compression plating
      remains an effective treatment option for nonunion of humeral shaft fracture.
      Level of Evidence III, Retrospective study.

PMID- 24453608
TI  - Use of the tendon of the palmaris longus muscle in surgical procedures: study on
      cadavers.
AB  - OBJECTIVE: Demonstrate that the tendon of palmar long can be estimated in
      relation to its length and width before using it as a graft in surgical
      procedure. METHODS: There were examined 60 forearms of 30 corpses of black
      ethnicity; measure the length and width of the tendon of the palmaris longus
      muscle and compared the length of the forearm. RESULTS: There are notes their
      absence unilateral right in two female corpses. The medium length and width were
      more or less respectively 11.9, 15.2 mm and 4.1 + 1.5 mm. The total average
      forearm length of 275.4 was more or less 17.9 mm. CONCLUSION: There is a
      significant relationship between the length of the tendon and the length of the
      forearm; so we can evaluate the size of the tendon of the palmaris longus muscle
      when it is necessary to use it for grafts. Levels of Evidence IV, Case series.

PMID- 24453609
TI  - Study on implant stability in cementless total knee arthroplasty.
AB  - OBJECTIVES: Determine the stability of tibial and femoral components of 20
      cementless knee arthroplasties with rotating platform. METHODS: The 20 patients
      (20 knees) underwent an analysis of dynamic radiographs with an image amplifier
      and maneuvers of varus and valgus which were compared to static frontal and
      lateral radiographs of the knees and analyzed by two experienced surgeons in a
      double-blind way. RESULTS: We could observe in this study that both methods
      showed very similar results for the stability of the tibial and femoral
      components (p<0.001) using the Kappa method for comparison. CONCLUSION: The
      tibial component was more unstable in relation to the femoral component in both
      static and dynamic studies. Level of Evidence IV, Case Series.

PMID- 24453610
TI  - Follow-up of treated osteosarcoma patient.
AB  - OBJECTIVE: To evaluate the value of post-treatment follow-up in osteosarcoma
      patients. METHODS: Data were collected through a clinical record, with socio
      demographic and clinical data, and information relating to the medical
      appointment. Descriptive analysis of the data was carried out. The Chi-squared
      test was used to associate the independent variables with attendance at scheduled
      follow-up appointments. RESULTS: We found a recurrence in 59.6% of cases, of
      which 58% were lung related; 44% presented clinical complaints and arrived on the
      scheduled date of the appointment. There was no statistically significant
      association between the demographic characteristics and early attendance of
      follow-up visits. 81.3% of the cases who came for the appointment earlier than
      originally scheduled presented complaints compared to those who did not
      (p=0.005). Of the cases who presented recurrence, 12.9% attended an appointment
      late and those who did not present recurrence, 47.6% were late for the
      appointment (p=0.006). CONCLUSION: It is seen that the patients who came for an
      earlier appointment presented more complaints and were associated with the
      positive result of the exams carried out. The patients who had recurrence and
      came for an earlier appointment did not present a statistically significant
      difference in recurrence-free survival. It was observed that distance was not a
      predominant factor in late attendance at appointments. Level of Evidence II,
      Retrospective Study.

PMID- 24453611
TI  - Thoracolumbar burst fracture: radiographic evaluation on differences between
      Magerl's A and B.
AB  - OBJECTIVE: Evaluate incidence of Magerl's A and B group in thoracolumbar burst
      fracture (Denis) according to independent examiners. METHOD: According to the
      posterior spinous process split on the anterior posterior radiography, three
      independent examiners have analyzed the patients admitted from 2000 to 2009 with
      thoracolumbar burst fractures (according to Denis) to differentiate between
      Magerl's type A3 and B1.2. Statistical evaluation was descriptive and by using
      Kappa's method. RESULTS: From the 72 patients, 11 patients compose the Magerl's
      type B group according to examiner 1; 10 according to examiner 2; and 17
      according to examiner 3. Posterior lesion concordance was satisfactory (good,
      kappa=0.7) between the examiners. CONCLUSION: 14 to 24% patients with
      thoracolumbar fractures show posterior lesion (B1.2) by using radiographic
      criteria. Level of evidence III, Diagnostic Studies Investigating a Diagnostic
      Test.

PMID- 24453612
TI  - Editorial.

PMID- 24453613
TI  - Intra-articular bupivacaine or bupivacaine and morphine after ACL reconstruction.
AB  - OBJECTIVE: Reconstructive surgery of the ACL is one of the most commonly
      performed surgeries today and the control of postoperative pain is part of the
      priorities of the surgeon. Within the arsenal of analgesia we have the intra
      articular application of drugs, and the most studied one is bupivacaine with or
      without morphine. This study compared the application of bupivacaine with or
      without morphine with a control group after ACL reconstruction with flexor tendon
      graft. METHODS: Forty-five patients were randomized into three groups: in group
      I, 20 ml of saline were applied intra-articularly at the end of the surgery; in
      group II, 20 ml of bupivacaine 0.25%; and in group III, bupivacaine 0.25%
      associated with 1 mg of morphine. The groups were assessed for degree of pain by
      the Visual Analog Scale at 6, 24 and 48 hours postoperatively. RESULTS: Group III
      had less pain at all times, but the pain was not as intense in all groups to the
      point of needing extra medications beyond the established protocol. CONCLUSION:
      The intra-articular application of these medications after ACL reconstruction
      with flexor tendon graft when performed under spinal anesthesia is not useful
      enough to use regularly. Level of Evidence II, Lesser quality RCT.

PMID- 24453614
TI  - Intramedullary screw fixation of proximal fifth metatarsal fractures in athletes.
AB  - OBJECTIVE: The purpose of this study was to review the short- and long-term
      clinical and radiological results of intramedullary compression screw fixation of
      proximal fifth metatarsal fractures in athletes. METHODS: Eleven male and six
      female active patients with fifth metatarsal zone II and zone III fractures fixed
      with a 4.5-mm cannulated compression screw were evaluated by chart review, review
      of radiographs, and clinical evaluation. Fifteen of the patients were high-level
      athletes (soccer: n=11; basketball: n=1; track and field: n=3) and two were
      recreational-level athletes. Mean follow-up from surgery to evaluation was 54 (38
      70) months. RESULTS: Mean time to healing as shown on radiographs and mean time
      to return to full activity after surgery were 7.3 and 7.5 weeks, respectively.
      All patients were able to return to their previous levels of activity. There were
      no reports of union delay, nonunion or refracture to date. CONCLUSION: In our
      patients, cannulated screw fixation of proximal fifth metatarsal fractures was a
      reliable procedure with low morbidity associated that provided athletes a quick
      return to activity. Level of Evidence I, Case Series .

PMID- 24453615
TI  - Alterations in the Achilles tendon after inflammation in surrounding tissue.
AB  - OBJECTIVE: To analyze the characteristics of the Achilles tendon of rats after
      induction of localized inflammation in the rat paw. METHODS: IN OUR STUDY THREE
      GROUPS WERE USED: inflamed group with carrageenan in rat paw (G1); saline group
      (G2) and control group (G3). After 4 hours the animals were euthanized and the
      Achilles tendon removed. RESULTS: No significant differences were observed in the
      analysis of non-collagenous proteins, glycosaminoglycans and hydroxyproline in
      the groups but a tendency of reduction was verified in G1. As regards the
      organization of collagen molecules, no differences were observed between groups.
      With respect to MMPs activity, a stronger presence of the active isoform of MMP-2
      in G1 was observed, suggesting that the remodeling was occurring. CONCLUSION:
      Thus, we conclude that the inflammatory process in rat paw may affect the
      remodeling of tendons located near the inflamed site. Level of Evidence I,
      Prognostic Studies - Investigating the Effect of a Patient Characteristic on the
      Outcome of Disease.

PMID- 24453616
TI  - Cell therapy of pseudarthrosis.
AB  - OBJECTIVE: To assess the safety and efficiency of cell therapy for
      pseudarthrosis. Implant of the bone marrow aspirate was compared to mononuclear
      cells purified extemporaneously using the Sepax((r)) equipment. METHODS: Six
      patients with nonunion of the tibia or femur were treated. Four received a
      percutaneous infusion of autologous bone marrow aspirated from the iliac crest,
      and two received autologous bone marrow mononuclear cells separated from the
      aspirate with the Sepax((r)). The primary fixation method was unchanged, and the
      nonunion focus was not exposed. Physical examination and radiographies were
      performed 2, 4 and 6 months after the treatment by the same physician. After
      consolidation of the fracture the satisfaction of the patients was estimated
      using the adapted QALY scale. RESULTS: No complications occurred as a result of
      the referred procedures. Bone consolidation was obtained in all cases within 3 to
      24 weeks. The degree of patient satisfaction before and after bone consolidation
      was assessed, with the average value increasing from two to nine (p=0.0156).
      CONCLUSION: We conclude that the proposed method is effective and safe for the
      treatment of nonunion of long bones regardless of the stabilization method used.
      Level of Evidence II, Prospective Comparative Study.

PMID- 24453617
TI  - Effect of the pilot hole preparation on the anchorage of pedicle screws.
AB  - OBJECTIVE: We evaluated the influence of the diameter and the preparation of the
      pilot hole on the resistance to the pulling out and the strength when inserting
      pedicle screws with conical internal diameter. METHODS: Mechanical experiments
      were performed with pedicle conical screws of 4.2 mm and 5.2 mm diameter. They
      were inserted in the vertebral pedicles of swine. The hole was manufactured with
      a drill and probes with different diameters. RESULTS: While testing the 4.2 mm
      screw, the perforation of holes with measure equal or inferior to the lesser
      internal diameter of the screw increased the torque and the resistance to pull
      out strength. Perforations with different instruments have presented similar
      results. Perforations with probes allowed the holes manufactured with dimensions
      superior to the lesser internal diameter of the screw to show similar resistance
      to that of the perforations with dimensions equal to the lesser internal diameter
      of the implant, made with probes and drills. CONCLUSION: For 4.2 mm screws, the
      diameter and the preparation of the hole influence the torque and the resistance.
      For 5.2 mm screws, there is only influence on the insertion torque. There is no
      correlation between pulling out strength and insertion torque. Level of Evidence
      II, Therapeutic Studies - Investigating the Results of Treatment.

PMID- 24453618
TI  - Simple suture and anchor in rabbit hips.
AB  - OBJECTIVE: USING BIOMECHANICAL STUDIES, THIS RESEARCH AIMS TO COMPARE HIP
      CAPSULORRHAPHY IN RABBITS, CARRIED OUT WITH TWO DIFFERENT TECHNIQUES:
      capsulorrhaphy with simple sutures and with anchors. METHOD: Thirteen New Zealand
      Albino (Oryctolaguscuniculus) male rabbits, twenty-six hip joints, were used.
      First, a pilot project was performed with three rabbits (six hip joints). This
      experiment consisted of ten rabbits divided into two groups: group 1 underwent
      capsulorrhaphy on both right and left hips with simple suture using polyglycolic
      acid absorbable thread, and group 2 underwent capsulorrhaphy with titanium
      anchors. After a four-week postoperative period, the animals were euthanized and
      the hip joints were frozen. On the same day of the biomechanical studies, after
      the hip joints were previously unfrozen, the following parameters were evaluated:
      rigidity, maximum force, maximum deformity and energy. RESULTS: There was no
      relevant statistical difference in rigidity, maximum force, maximum deformity and
      energy between the simple suture and anchor groups. CONCLUSION: Through
      biomechanical analyses, using parameters of rigidity, maximum force, maximum
      deformity and energy, it has been shown that capsulorrhaphy with simple suture
      and with anchors has similar results in rabbit hip joints. Level of Evidence II,
      Prospective Comparative Study .

PMID- 24453619
TI  - Effectiveness of cryotherapy after anterior cruciate ligament reconstruction.
AB  - OBJECTIVE: The purpose of this study was to evaluate cryotherapy effectiveness in
      the immediate postoperative period of ACL reconstruction to improve pain and
      range of motion (ROM) of the knee. METHODS: This is a pilot study of a
      prospective and randomized clinical trial. Patients (n=25) were divided into two
      groups: Intervention (A) group (n=10): patients were submitted to an inpatient
      physical therapy protocol and received ice compress for 20 minutes, twice a day;
      Control (B) group (n=9): patients had the same protocol, twice a day. The pain
      intensity was evaluated with the visual analogic scale (VAS) and range of motion
      was measured with a goniometer. RESULTS: The Intervention (A) group had important
      absolute and percentual improvement when compared with the Control (B) group
      regarding measures of pain and knee flexion/extension ROM. CONCLUSION:
      Cryotherapy in the immediate postoperative period of ACL reconstruction was
      effective to improve pain and range of motion of the knee. Level of Evidence I,
      Randomized Clinical Trial .

PMID- 24453620
TI  - Clinical assessment and magnetic resonance imaging of the shoulder of patients
      with spinal cord injury.
AB  - OBJECTIVE: To study the shoulder of this group of patients using magnetic
      resonance imaging to detect clinical and subclinical disorders and establish a
      rehabilitation program. METHODS: Nine patients with spinal cord injury followed
      in the Laboratory of Biomechanics and Rehabilitation of the Locomotive System at
      HC/UNICAMP were divided into two groups according to the presence of paraplegia
      and tetraplegia and were clinically assessed for correlation with the imaging
      exams. RESULTS: Normal results were found in 41% of the shoulders. Most common
      injuries were tendinopathy of the supraspinatus and acromioclavicular joint
      degeneration. Eighty percent of injured shoulders had combined lesions.
      CONCLUSION: A great variety of causes of shoulder pain was identified in
      paraplegic and tetraplegic subjects. Routine clinical assessment and imaging
      studies of the shoulder may contribute to the evolution of rehabilitation and
      reduction of pain and musculoskeletal disorders. Level of Evidence II,
      Development of Diagnostic Criteria on Consecutive Patients, With Universally
      Applied Reference "Gold" Standard.

PMID- 24453621
TI  - Surgical treatment of mallet fractures by extension block Kirschner wire
      technique surgical treatment of mallet fractures.
AB  - OBJECTIVE: We use the extension block Kirschner wire method that orginated from
      Ishigura to treat mallet fracture and evaluate its efficiency. METHODS: 38
      patients were treated prospectively. Mean follow-up was 18 months and all
      patients evaluated radiologically and clinically according to Crawford's
      criteria. RESULTS: Union was obtained in all patients. The results obtained were
      satisfactory in 34 cases, unsatisfactory 4 cases. CONCLUSION: We think that
      extension block technique is a safe and effective method that can be used in all
      mallet fractures. LEVEL OF EVIDENCE: Level IV, Case series .

PMID- 24453622
TI  - Results of total knee replacement with/without resurfacing of the patella.
AB  - OBJECTIVE: To study the difference of post-op patellofemoral pain, clunk and
      crepitus in patients with/without resurfacing at 5 years who had pre-op
      patellofemoral pain. To study the incidence of post-operative patellofemoral
      pain, clunk and crepitus following patelloplasty in both the groups. METHODS:
      Retrospective review of 765 patients who had total knee replacement with/without
      resurfacing.Patients were asked about both pre-operative pain and also post
      operative pain 5 years after the operation. Patients were examined by a
      specialist nurse at 5 years post-operatively to check for any patellofemoral
      clunk/crepitus. CONCLUSION: In patients with pre-op PF pain, there is significant
      (p<0.005) higher incidence of post-op clunk in the R group. In patients without
      pre-op PF pain, there is significantly (p<0.005) higher incidence of post-op
      crepitus in the R group. In patients with/without pre-op PF pain, the incidence
      of post-op PF pain, clunk and crepitus is lower than in patients who underwent
      patelloplasty when compared to the other members of the NR group (statistically
      significant p<0.005). LEVEL OF EVIDENCE: Type 4, Case series .

PMID- 24453624
TI  - Results of ulnar nerve neurotization to biceps brachii muscle in brachial plexus
      injury.
AB  - OBJECTIVE: To evaluate the factors influencing the results of ulnar nerve
      neurotization at the motor branch of the brachii biceps muscle, aiming at the
      restoration of elbow flexion in patients with brachial plexus injury. METHODS: 19
      patients, with 18 men and 1 woman, mean age 28.7 years. Eight patients had injury
      to roots C5-C6 and 11, to roots C5-C6-C7. The average time interval between
      injury and surgery was 7.5 months. Four patients had cervical fractures
      associated with brachial plexus injury. The postoperative follow-up was 15.7
      months. RESULTS: Eight patients recovered elbow flexion strength MRC grade 4;
      two, MRC grade 3 and nine, MRC <3. There was no impairment of the previous ulnar
      nerve function. CONCLUSION: The surgical results of ulnar nerve neurotization at
      the motor branch of brachii biceps muscle are dependent on the interval between
      brachial plexus injury and surgical treatment, the presence of associated
      fractures of the cervical spine and occipital condyle, residual function of the
      C8-T1 roots after the injury and the involvement of the C7 root. Signs of
      reinnervation manifested up to 3 months after surgery showed better results in
      the long term. LEVEL OF EVIDENCE: IV, Case Series.

PMID- 24453625
TI  - Design of butterfly-shaped plate and its application in treatment for calcaneal
      fractures.
AB  - OBJECTIVE: To introduce the design of a butterfly-shaped plate and its
      application in the treatment of calcaneal fractures, and to discuss its clinical
      indications, advantages and disadvantages. METHODS: From February 2008 to April
      2010, 22 patients with 26 intra-articular calcaneal fractures were treated by
      open reduction and internal fixation with a butterfly-shaped plate. Sixteen
      patients were male and six patients were female, with a mean age of 36.8 years.
      Eleven were left feet and 15, right. According to the Sanders classification, 12
      were calcaneal fractures Type II (including three Type IIa, seven Type IIb and
      two Type IIc) and 14 were Type III (including five Type IIIab, seven Type IIIac
      and two Type IIIbc). RESULTS: Seventeen patients (21 feet) were followed-up for
      an average of 19.2 months. The functional outcomes were assessed using the
      Maryland Foot Score system. Among the nine feet with Type II fractures, seven
      feet were scored excellent, two were good. Among the 12 Type III fractures, six
      were scored excellent, five were good, and one was scored fair. CONCLUSION: The
      butterfly-shaped plate is applicable in the treatment of Sanders Type II and Type
      III calcaneal fractures, with the advantages of ensuring reliable fixation,
      facilitating the surgery, producing fewer postoperative complications, and
      generating better overall clinical outcomes. Level of Evidence IV, Case Series.

PMID- 24453626
TI  - Treatment of femoral subtrochanteric fractures with proximal lateral femur
      locking plates.
AB  - OBJECTIVE: To study the outcome of subtrochanteric hip fractures treated with
      proximal lateral femur locking plate. METHOD: We retrospectively reviewed the
      clinical results of 48 cases of femoral subtrochanteric fractures treated with
      proximal lateral femur locking plates from January 2008 to May 2010. The progress
      of fracture healing, as well as the occurrence of complications, was recorded.
      The function of the hip joint was evaluated by the Harris social index and the
      Parker and Palmer mobility score one year after the operation. RESULT: 45
      patients were followed up until fracture union or a revision surgery. Among the
      45 patients, 43 patients obtained fracture union without further intervention.
      Thirty-eight fractures healed with no loss of position at 1-year follow-up. There
      were no cases of hip screw cutting through the femoral head. The mean score of
      the Harris social index was 86.5+/-9.8 (73~95). The mean Parker and Palmer
      mobility score was 7.4+/-2.1 (3~9). CONCLUSION: The proximal lateral femur
      locking plate is the kind of stable and effective internal fixation for treating
      subtrochanteric hip fractures which has the advantage of stable fixation
      especially for the lateral femoral wall fracture. Level of Evidence IV, Case
      Series.

PMID- 24453627
TI  - Anatomical and functional study of the medial collateral ligament complex of the
      elbow.
AB  - OBJECTIVE: To carry out an anatomical study of the medial collateral ligament, an
      important elbow stabilizer in different degrees of elbow flexion-extension.
      METHODS: Forty elbows were dissected in order to analyze the functional behavior
      of the anterior, posterior and transverse ligament bands during valgus stress
      maneuvers of the elbow in different degrees of flexion and extension. Two groups
      were determined; in the group GPA the posterior band of the ligament was
      sectioned initially, then the articular capsule and finally the anterior band; in
      group GAP this order was reversed. RESULTS: Instability was observed in GPA only
      in the third stage, when there was a greater mean elbow's opening during the
      flexion (between 50 degrees  and 70 degrees ); in GAP, the instability was
      present since the first stage; the degrees of flexion with greater instability
      were the same as in group GPA. CONCLUSION: The anterior band of the medial
      collateral ligament of the elbow is the most important stabilizer of the elbow
      valgus instability, and its principal action occurs between 50 degrees  and 70
      degrees  of elbow flexion. Level of Evidence III, Diagnostic Studies -
      Investigating a diagnostic test.

PMID- 24453628
TI  - Epidemiological study of foot and ankle injuries in recreational sports.
AB  - OBJECTIVE: This is a retrospective study showing the incidence, type and extent
      of injuries occurring in the foot and/or ankle as a result of recreational sports
      practice. METHODS: We treated 131 patients, of which 123 were male and 8 female,
      with a history of trauma and pain in the foot and/or ankle after the practicing
      recreational sports. The average age of the male patients was 24.53 years. The
      evaluation was done through a research protocol, which contained the variables
      age, sex, diagnosis, and type of recreational sport. RESULTS: The sports were
      classified according to the American Medical Association, which divides them into
      contact and non-contact sports. 82.4% of the sample practiced contact sports,
      while 17.6% practiced sports classified as non-contact. CONCLUSIONS: The sprained
      ankle was the most frequent type of injury, especially those of grade I and II.
      Soccer was the sport responsible for the highest incidence of injuries and among
      its various forms the indoor soccer presented the highest frequency of injuries
      (35%). In the non-contact sports, the highest incidence was found in running.
      Level of Evidence IV, Case Series.

PMID- 24453629
TI  - Bone mineral density estimated by osteorisk in patients with adolescent
      idiopathic scoliosis.
AB  - OBJECTIVE: The prevalence of osteoporosis in patients with Adolescent Idiopathic
      Scoliosis (AIS) is believed to be higher than in the general adolescent
      population. An alternative to radiology for the characterization of bone mineral
      density may be through correlative indexes like the Osteorisk index, which is
      easy to access and low in cost, and which helps the doctor in the request for
      Bone Densitometry. Our belief that osteoporosis can affect the evolution and
      treatment of AIS was what motivated us to conduct this study. Our objective was
      to subjectively evaluate bone mineral density by the Osteorisk index in patients
      with AIS. METHODS: Healthy patients (control group, n=30) and patients with AIS
      (n = 30) were evaluated, documenting age, weight and height, and establishing the
      Osteorisk. The unpaired Student t test was performed, with a level of
      significance of p <0.05. RESULTS: The mean Osteorisk found for the patients with
      AIS was 6.38 +/- 2.2 while in the control group, it was 8.27 +/- 2.14, which
      represents a low risk of developing osteoporosis in both groups. Comparing these
      means between the groups, a lower Osteorisk was observed in the AIS group.
      CONCLUSION: Our study showed that there is low risk of developing osteoporosis in
      patients with AIS. Level of Evidence I, Prospective study.

PMID- 24453630
TI  - Translation and cross-cultural adaptation of the rowe score for portuguese.
AB  - OBJECTIVE: To translate and culturally adapt the Rowe score for use in Brazil.
      METHODS: The translation and cross-cultural adaptation process initially involved
      the steps of translation, synthesis, back-translation and revision by the
      Translation Group. The pre-final version of the questionnaire was then created.
      The Stability and Function fields were applied to 20 patients with anterior
      shoulder luxation, and the Mobility field was applied to 20 health professionals.
      RESULTS: It was found that some of the patients had difficulty understanding some
      of the expressions of the questionnaire, so these were replaced with terms that
      were easier to understand. All health professionals understood the translation of
      the Mobility field. The altered questionnaire was then reapplied to another 20
      patients, and this time it was understood by all the assessed subjects.
      CONCLUSION: After a careful process of translation and cultural adaptation, a
      definitive version of the Rowe questionnaire was obtained in Brazilian
      Portuguese. Level of Evidence II, Development of diagnostic criteria on
      consecutive patients.

PMID- 24453631
TI  - Hallux valgus: comparative study between two surgical techniques of proximal
      addition osteotomy.
AB  - OBJECTIVE: TO CLINICALLY AND RADIOGRAPHICALLY COMPARE THE RESULTS OF TREATMENT OF
      HALLUX VALGUS, BY TWO ADDITION OSTEOTOMY TECHNIQUES: one using resected
      exostosis, and the other using a plate fixation for addition wedge. METHODS: We
      evaluated 24 feet of 19 patients, mean age 51.3 years, affected by hallux valgus,
      with a mean follow-up of 50.1 months. 13 feet underwent addition osteotomy with
      resected exostosis (AORE) and 11 patients (11 feet) underwent addition osteotomy
      with plate (AOP). The AOFAS score, intermetatarsal 1 and 2 angles, and hallux
      valgus angle were evaluated before and after surgery. RESULTS: In the AORE
      technique, the mean preoperative AOFAS was 46.6, with IMA 14(o) and HVA 32o,
      while in the postoperative AOFAS it was 81.3, with IMA 9(o) and HVA 25(o), and
      92.3% satisfactory results. In the AOP technique, the mean preoperative AOFAS was
      42.1, with IMA 15(o) and HVA 29(o) while in the postoperative AOFAS it was 77.4,
      with IMA 11(o) and HVA 23(o) and 81.8% of satisfactory results. CONCLUSIONS: Both
      techniques proved to be effective in the treatment of hallux valgus, both
      clinically and radiografically, with no statistical difference between them.
      Level of evidence III, Retrospective comparative study.

PMID- 24453632
TI  - Exercise and its interactions with various aspects of man and animal lives.
AB  - To review recently published papers in the Brazilian Scientific press on the
      general subject of physical exercise. All articles published in 2010/2011 found
      through the keyword exercise were collected from 11 Brazilian Journals. They were
      hand filtered to exclude all but original research papers. They were grouped
      according to subject categories and subcategories. A brief summary of all
      included articles was produced, comparing similar articles between them. The most
      commonly found interactions refer to exercise vs. the cardiovascular system,
      metabolism and the locomotor system, in this order. The volume of scientific
      research in the field is high and of sufficient quality to justify highlighting. 

PMID- 24453633
TI  - A survey of recently published papers on orthopedics in the Brazilian scientific
      press.
AB  - This paper is a review of articles published in Brazilian scientific periodicals
      in recent years. Its main purpose is to bring to the attention of the readership
      of Acta Ortopedica Brasileira original contributions to the field published in
      non-specialized journals. We hope that this will serve as a general scientific
      update for readers. The review includes works published in six ISI indexed non
      orthopedic journals, following a literature search conducted in fourteen such
      journals. 

PMID- 24453634
TI  - Physiotherapy after reconstruction of anterior cruciate ligament.
AB  - The purpose of this study was to evaluate the existence of differences in the
      rehabilitation of patients after ACL reconstruction using bone-patellar tendon
      bone graft and the four-strand semitendinosus and gracilis tendon grafts, through
      a literature revision. The researched databases were MEDLINE, EMBASE, LILACS,
      COCHRANE and PEDro. The inclusion criteria were published studies with
      methodology draw from randomized clinical trials with or without meta-analysis,
      individuals with ACL injury, associated or not to meniscal injury, submitted to
      ligamentoplasty using the bone-patellar tendon-bone graft and the four-strand
      semitendinosus and gracilis tendon grafts and physiotherapy; clinical trials
      comparing the differences in the rehabilitation of these patients, in Portuguese,
      English and Spanish, from 1990 to June, 2011. Five clinical trials were reviewed.
      No difference was observed between the techniques, however, with a recommendation
      for a less aggressive rehabilitation and greater attention to the strengthening
      of the hamstring when they are used as grafts. 

PMID- 24453635
TI  - Editorial.

PMID- 24453636
TI  - Viscosupplementation in patients with hemophilic arthropathy.
AB  - OBJECTIVE: To assess whether viscosupplementation with hyaluronic acid in
      patients with severe hemophilic arthropathy associated with triamcinolone after
      washing with saline improves joint pain, stiffness, function and quality of life.
      METHODS: Eleven patients with hemophilic arthritis of the knee with and without
      involvement of other joints (elbows and ankles) underwent joint lavage with
      saline and subsequent injection of Hylan and triamcinolone in all affected
      joints. The patients answered the algo-functional (Lequesne and WOMAC), visual
      analog scale for pain (VAS) and SF-36 (quality of life) questionnaires
      preoperatively, and at one and three months postoperatively. RESULTS: Pain (VAS
      and WOMAC pain) and stiffness (WOMAC stiffness) did not show significant
      improvement (p = 0.3, p = 0.2, p = 0.1, respectively). However function had
      significant improvement given by WOMAC total and function (averaging 11 points, p
      = 0.04 and p = 0.001). There was no significant variation in scores in Lequesne's
      questionnaire (p = 0.1), yet both mental and physical components of SF-36
      presented clinically relevant and significant improvements (p = 0.002).
      CONCLUSION: Joint lavage with saline followed by injection of corticosteroids and
      Hylan is effective in the treatment of hemophilic arthropathy, especially in
      functional improvement and quality of life. Level of Evidence IV, Case series.

PMID- 24453637
TI  - The effect of low-intensity therapeutic ultrasound in induced fracture of rat
      tibiae.
AB  - OBJECTIVE: To analyze the possible effects of low-intensity ultrasound on induced
      tibia fracture of rats in a dose commonly used in physical therapy treatments.
      METHODS: Twenty male Wistar rats were divided into two groups with 10 animals
      each. In the ultrasound group (USG), the animals were submitted to bone fracture
      and treatment with therapeutic ultrasound (TUS). Ultrasonic parameters are:
      frequency of 1.0 MHz, intensity of 0.2 W/cm2, pulsed mode at 20%, applied in
      stationary form during 10 minutes on the fracture region, for five weeks. The
      control group (CG) was submitted to bone fracture but not treated with
      ultrasound. RESULTS: The radiographies showed better consolidation in USG
      compared to CG. The statistical tests for alkaline phosphatase and serum calcium
      did not show significant difference between groups. CONCLUSION: According to this
      study, TUS, applied with these parameters (not commonly used for bone therapy)
      accelerates bone healing, confirmed by radiography, yet the biochemical analysis
      was not conclusive. One reason for this inconsistency may have been some
      inadequacy of the biochemical protocol, currently under investigation. Level of
      Evidence II, Prospective comparative study.

PMID- 24453638
TI  - Results of revision total knee arthroplasty using press-fit cementless stem.
AB  - OBJECTIVE: To show our experience with press-fit cementless stem and metaphyseal
      fixation with cement in a selected series of patients who underwent revision
      total knee arthroplasty. METHODS: Thirty-four patients (35 knees) underwent
      revision total knee arthroplasty using the press-fit technique. Minimum follow-up
      was one year (mean 2.2 years) with a maximum length of three years. RESULTS: Of
      34 patients, 20 were women and 14 were men. There was one death due to causes not
      related to arthroplasty and one patient dropout. There were no cases in which
      further review was necessary. Patients who underwent revision had clinical and
      functional improvement demonstrated by the results of the KSS, results of the SF
      36 quality of life questionnaire, through gains in range of motion and improved
      limb alignment. CONCLUSION: There was postoperative clinical and functional
      improvement in comparison to the preoperative status in revision total knee
      arthroplasty with press-fit cementless stem. Level of Evidence IV, Case series.

PMID- 24453639
TI  - Pain, kinesiophobia and quality of life in chronic low back pain and depression.
AB  - OBJECTIVE: To describe the characteristics of pain, kinesiophobia and quality of
      life in patients with chronic low back pain and depression. METHODS: Cross
      sectional study in which 193 individuals with chronic low back pain were
      included. The presence of depression was measured by the Beck Depression
      Inventory, using a cutoff validated by the Mini International Neuropsychiatric
      Interview. The intensity and quality of pain in the groups with and without
      depression were assessed by the McGill Questionnaire. The Tampa Scale for
      Kinesiophobia was applied to assess fear of movement. With respect to quality of
      life, the Medical Outcomes Study 36 was used. The statistical significance level
      was set at p <0.05. RESULTS: The prevalence of depression was 32.1%. The group
      with depression had worse scores in relation to pain, kinesiophobia and quality
      of life (physical functioning, rolephysical, bodily pain, general health,
      vitality, social functioning, role-emotional, and mental health. CONCLUSION:
      Patients with low back pain and depression had higher pain intensity, greater
      fear of movement and poorer quality of life. Level of Evidence III, Cross
      sectional.

PMID- 24453640
TI  - Radiographic grading of femoral stem cementation in hip arthroplasty.
AB  - OBJECTIVE: To determine intra and interobserver agreement of the grading system
      for femoral cementation in hip arthroplasty proposed by Barrack. METHODS:
      Immediate anteroposterior and lateral postoperative radiographs of 55 primary
      total hip arthroplasties were assessed by two observers familiar with the use of
      this grading system. The assessments were performed on two separate occasions by
      each observer and independently. The statistical analysis measured the Kappa
      coefficient, which determines the degree of agreement between tests with
      categorical variables. RESULTS: Intraobserver Kappa coefficient varied from 0.43
      to 0.68, demonstrating moderate to substantial strength of agreement;
      interobserver Kappa coefficient varied from 0.19 to 0.44, demonstrating slight to
      moderate strength of agreement. CONCLUSION: Intra and particularly interobserver
      agreement are limited in this grading system, even when used by trained
      individuals. Level of Evidence III, Study of nonconsecutive patients; without
      consistently applied reference "gold" standard.

PMID- 24453641
TI  - Biomechanics of four techniques for fixation of the four-part humeral head
      fracture.
AB  - OBJECTIVE: To carry out a biomechanical study of four techniques for fixation of
      four-part humeral head fractures. METHODS: The fracture was reproduced in 40
      plastic humeri, divided into groups of ten according to the fixation technique,
      each one employing different fixation resources, in different configurations. The
      humeral models were mounted on an aluminum scapula, with leather straps
      simulating the rotator cuff tendons, and submitted to bending and torsion tests
      in a universal testing machine, using relative stiffness as an evaluation
      parameter. Assemblies with intact humeri were analyzed for comparison. RESULTS:
      The biomechanical behavior of the fixation techniques varied within a wide range,
      where the assemblies including the DCP plate and the 4.5mm diameter screws were
      significantly more rigid than the assemblies with the Kirschner wires and the
      3.5mm diameter screws. CONCLUSION: The four fixation techniques were able to bear
      loads compatible with the physiological demand, but those with higher relative
      stiffness should be preferred for clinical application. LABORATORY INVESTIGATION:
      .

PMID- 24453642
TI  - New method of preoperative immobilization for the proximal femoral fractures.
AB  - OBJECTIVE: To evaluate the efficacy of a new method of provisional preoperative
      imobilization for patientes with transtrochanteric femoral fractures. METHODS:
      Over a three-month period, 33 patients were treated at the Orthopaedic Trauma
      Service for transtrochanteric femoral fracture. We selected 22 patients and they
      were divided into groups with and without the use of the developed imobilization.
      The patients were evaluated according to the Visual Analogue Scale for Pain (VAS)
      during the preoperative and postoperative period in order to verify the analgesic
      consume and clinical complications. RESULTS: The group that used the
      imobilization had lower pain, reduced analgesic consume and had less clinical
      complications. CONCLUSION: The new imobilization therefore presents good results,
      however not statistical significant. Level of Evidence II, Prospective
      Comparative Study.

PMID- 24453643
TI  - Coagulation disorders in patients with femoral head osteonecrosis.
AB  - OBJECTIVE: To compare the occurrence of thrombophilic disorders in patients with
      idiopathic osteonecrosis of the femoral head and patients with secondary
      osteonecrosis of the femoral head. METHODS: Twenty-four consecutive patients were
      enrolled, with eight of them presenting idiopathic osteonecrosis and 16
      presenting secondary osteonecrosis. The tests for detection of thrombophilic
      disorders were measurements of protein C, protein S and antithrombin levels and
      detection of prothrombin and factor V gene mutations. We compared the results
      using the odds ratio statistics for the thrombophilic disorders between the two
      groups. RESULTS: The odds ratio for the protein S deficiency and protein C
      deficiency between the idiopathic and secondary groups were 5 and 2.14,
      respectively. Thus, an individual with idiopathic osteonecrosis has 5 times more
      chance of presenting protein S deficiency and 2.14 times more chance of
      presenting protein C deficiency than an individual with secondary osteonecrosis.
      CONCLUSION: Patients with idiopathic osteonecrosis have more chances of
      presenting thrombophilias than those with secondary osteonecrosis, suggesting
      these coagulation disorders can play an important role in the pathogenesis of the
      osteonecrosis in cases where there was no initial risk factor recognized. Level
      of Evidence III, Case-Control Study.

PMID- 24453644
TI  - Ultrasonometry evaluation of axial compression osteosinthesis. An experimental
      study.
AB  - OBJECTIVE: To measure the ultrasound propagation velocity (UV) through a tibial
      transverse osteotomy in sheep, before and after the fixation with a DCP plate.
      MATERIAL AND METHODS: Ten assemblies of a DCP plate with the diaphyseal segment
      of tibiae, in which a transverse osteotomy was made, were used. Both coronal and
      sagittal transverse and the axial UV were measured, first with the intact bone
      assembled with the plate and then with the uncompressed and compressed osteotomy;
      statistical comparisons were made at the 1% (p<0.01) level of significance.
      RESULTS: Compared with the intact bone assembly, axial UV significantly decreased
      with the addition of the osteotomy and significantly increased with compression,
      presenting the same behavior for the other modalities, although not
      significantly. DISCUSSION AND CONCLUSION: In accordance with the literature data
      on the ultrasonometric evaluation of fracture healing, underwater UV measurement
      was able to demonstrate the efficiency of DCP plate fixation. The authors
      conclude that the method has a potential for clinical application in the
      postoperative follow-up of DCP plate osteosinthesis, with a capability to
      demonstrate when it becomes ineffective. Laboratory investigation.

PMID- 24453645
TI  - Neuromuscular electric stimulation in patellofemoral dysfunction: literature
      review.
AB  - Patellofemoral dysfunction is a fairly common deficiency among young individuals
      that primarily affects females and may be characterized by pain, swelling and
      retropatellar crepitation. The purpose of this review of literature from the
      period between 2005 and 2011 was to systematize knowledge in relation to the
      increase in quadriceps muscle strength and pain relief in patients with
      patellofemoral dysfunction, using neuromuscular electrical stimulation and
      resistance exercises. The inclusion criteria were intervention articles from the
      past six years, in English, Spanish and Portuguese, which used muscle
      strengthening and neuromuscular electrical stimulation for rehabilitation
      obtained through searches in the electronic databases Medline and Lilacs and in
      the Bireme library. The bibliographic search yielded 28 references, of which nine
      were excluded in accordance with the aims and inclusion criteria while 16
      articles were selected for reading of the abstracts and subsequent analysis.
      Mediumfrequency Neuromuscular Electrical Stimulation (NMES) can be used in
      association with resistance exercises as an adjuvant in the treatment of
      patellofemoral dysfunction (PFD), both to achieve muscle rebalance and for pain
      relief. 

PMID- 24453646
TI  - Hallux Rigidus: prospective study of joint replacement with hemiarthroplasty.
AB  - OBJECTIVE: To report the results of medium-term follow-up after deploying
      Arthrosurface-HemiCap((r)) in patients with diagnosis of Hallux Rigidus (HR).
      METHOD: Eleven patients underwent partial Arthroplasty of the first metatarsal
      phalangeal joint. Six women and five men with an average age 51.9 years (46 to 58
      years) and average postoperative follow-up of 3.73 years (3-4 years); were
      classified through the Kravitz system and evaluated by the American Orthopaedic
      Foot and Ankle Society (AOFAS) scales for hallux, Visual Analogical Scale (VAS) -
      analog functional pain - and range of motion in the first metatarsal joint in
      preoperative, postoperative after six months and present post-operative. RESULTS:
      The results show significant improvement of the three analyzed parameters, both
      for overall analysis and for pre and post-operative comparisons individually. The
      comparative analysis of each variable in the six months and the current
      postoperative periods do not show statistically significant differences,
      indicating maintenance of parameters during this interval. CONCLUSION:
      hemiarthroplasty of first metatarsophalangeal joint is a reproducible and safe
      option for the surgical treatment of hallux rigidus II and III, with significant
      improvement of the evaluated parameters for the studied population. Level of
      Evidence IV, Case Series.

PMID- 24453647
TI  - Technique and results after distal braquial biceps tendon reparation, through two
      anterior mini-incisions.
AB  - OBJECTIVE: Evaluation of postoperative results of repair of distal biceps brachii
      ruptures through a two anterior mini-incisions. METHODS: Nine patients with
      clinical and imaging (MRI) diagnosis of total lesion of the biceps brachii at its
      insertion were operated with a surgical technique with two mini-incisions between
      2008 and 2011. The patients were evaluated after three months of evolution and
      all of them recovered the fully flexion-extension arch. RESULTS: Two patients
      (22.2%) presented a limitation of 20 degrees of supination. One patient (11.1%)
      had radial nerve palsy, but was totally recovered after five months. In one
      patient (11.1%) the muscle remained retracted, but the insertion was recovered.
      In three patients (33.3%) adhesion was observed on the proximal scar. There was
      no clinical or radiographic evidence of radioulnar synostosis after six months of
      evolution. All patients reported satisfaction with the treatment. CONCLUSIONS: We
      conclude that the presented method shows good results as well as other
      techniques, with less risk of adhesion on the flexor fold of the elbow. Level of
      Evidence IV, Case Series.

PMID- 24453649
TI  - Transdermal monosialoganglioside with laser in the treatment of spinal cord
      lesion in rats.
AB  - OBJECTIVES: To evaluate the effects of monosialoganglioside (GM1) administered
      transdermally with laser in the recovery of spinal cord injury in rats. METHODS:
      Forty male Wistar rats underwent spinal cord contusion using the NYU Impactor. In
      Group 1, the rats received 0,2 ml of saline intraperitoneally daily; in Group 2,
      GM1 was administered intraperitoneally at a concentration of 30 mg/kg per day; in
      Group 3, rats were treated daily with laser at low temperature on the skin, and
      in Group 4, the daily laser session also contained GM1. All the groups were
      treated for 42 days. The animals were evaluated by the Basso, Baettie and
      Bresnahan (BBB) functional scale on days 7, 14, 21, 28, 35 and 42 after the
      injury, and by histopathology and motor evoked potential after 42 days of injury.
      RESULTS: The animals in Group 4 had higher BBB scores compared with the other
      groups. There were no differences between the groups, or in the comparisons over
      time. Histological evaluation showed no differences, and no differences were
      found in the motor evoked potential tests either. CONCLUSION: GM1 associated with
      the use of low-temperature laser shows no superior functional, neurological or
      histological results in the treatment of spinal cord lesions in rats. Evidence
      Level I, Experimental, Controlled, Animal Study.

PMID- 24453648
TI  - Platelet-rich plasma gel promotes regeneration of articular cartilage in knees of
      sheeps.
AB  - OBJECTIVE: To assess the regeneration of osteochondral defects in the joint
      cartilage of the knee induced by autologous platelet-rich plasma (PRP). METHODS:
      Osteochondral defects produced in the trochlear groove of both knees of ten
      sheep; defects of the right knees were filled with autologous PRP and the left
      knees were left unfilled. Macroscopic and microscopic evaluation was carried out
      12 week later. The results were evaluated by the total score of both macroscopic
      and microscopic evaluations comparing the two sides through the Wilcoxon paired
      test. RESULTS: Macroscopic appearance was not uniform among animals, nor was it
      different between the right and left knees (p=0.3125), and in no case the
      regenerated tissue was equal to the normal surrounding cartilage. At histological
      examination, apparently normal cartilage was not detected in any knee, but a
      poorly differentiated cartilage was present in 7 right knees, compared to 3 left
      knees. Fibrocartilaginous tissue was present in most of the remaining knees, with
      a significant difference in the overall score between right and left knees
      (p=0.0313). CONCLUSION: The PRP as used in this study has reparative properties
      of the joint cartilage of sheep knees, mostly by stimulating the formation of a
      fibrocartilaginous tissue. Laboratory investigation.

PMID- 24453650
TI  - Lack of effectiveness of laser therapy applied to the nerve course and the
      correspondent medullary roots.
AB  - OBJECTIVE: To investigate the influence of low intensity laser irradiation on the
      regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty
      five rats were used, divided into three groups: 1) intact nerve, no treatment; 2)
      crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the
      medullary region corresponding to the roots of the sciatic nerve and subsequently
      on the course of the damaged nerve. Laser irradiation was carried out for 14
      consecutive days. RESULTS: Animals were evaluated by functional gait analysis
      with the peroneal functional index and by histomorphometric analysis using the
      total number of myelinated nerve fibers and their density, total number of
      Schwann cells, total number of blood vessels and the occupied area, minimum
      diameter of the fiber diameter and G-quotient. CONCLUSION: According to the
      statistical analysis there was no significant difference among groups and the
      authors conclude that low intensity laser irradiation has little or no influence
      on nerve regeneration and functional recovery. Laboratory investigation .

PMID- 24453651
TI  - Shoulder arthroplasty in osteoarthritis: correlation between function and
      radiographic parameters.
AB  - OBJECTIVES: To evaluate the correlation between radiographic parameters and
      functional assessments of patients with osteoarthritis of the shoulder who
      underwent shoulder arthroplasty and to describe the functional outcomes of this
      procedure in our institution. METHODS: We evaluated 21 patients (22 shoulders)
      who underwent shoulder arthroplasty between 1998 and 2010 and with a minimum
      follow-up of 12 months. Clinical evaluation was performed using the Constant
      Murley scale, UCLA, EVA and by measuring the active motion. We analysed
      preoperative (distance between the top of the head and the humerus and the
      acromion, superior migration, neck angulation, medial "offset", subluxation,
      glenoid erosion) and postoperative radiographic parameters (rod inclination,
      migration of components and loosening). RESULTS: PATIENTS SHOWED SIGNIFICANT
      IMPROVEMENT IN ALL PARAMETERS: flexion (p = 0.0083), abduction (p = 0.0266),
      external rotation (p = 0.0062), Constant-Murley (p = 0.0001 ), UCLA (p <0.0001)
      and VAS (p = 0.0002). The superior migration of the humerus showed a significant
      correlation with UCLA and Constant-Murley scores (p = 0.0480 and p = 0.0110,
      respectively). The other radiographic parameters showed no correlation with the
      clinical outcomes. CONCLUSION: The superior migration of the humerus is related
      to worse clinical scores. Level of Evidence IV, Case Series.

PMID- 24453653
TI  - Epidemiological study on tibial plateau fractures at a level I trauma center.
AB  - OBJECTIVES: To review the epidemiological aspects of fractures of the tibial
      plateau in a level one hospital. METHODS: We retrospectively analyzed 239 tibial
      plateau fractures treated surgically. We took into account age, gender, trauma
      mechanism, classification of the injuries, associated injuries and affected side.
      RESULTS: 168 were male, the fifth decade has been the most affected, the
      mechanism of trauma, car accident was the main causal fator, 128 cases were on
      the left side and 22,6% had associated injuries. CONCLUSIONS: Most patients were
      male, in the fifth decade of life, and victim of traffic accidents, and the
      depression and shear fractures of the tibial plateau are the most frequent.
      Associated lesions were infrequent in our study. Level of Evidence II, Prognostic
      Studies. Investigating the Effect of a Patient Characteristic on the Outcome of
      Disease.

PMID- 24453652
TI  - Operative exploration and reduction of syndesmosis in Weber type C ankle injury.
AB  - OBJECTIVE: To investigate the surgical methods in treating Weber type C ankle
      injury and estimate the necessity of syndesmosis operative exploration. METHODS:
      Forty three patients of Weber type C ankle injury were treated with open
      reduction and internal fixation from October 2004 to December 2009. Twenty nine
      patients were treated with routine procedure by open reduction and internal
      fixation, syndesmosis exploration and repair were performed in addition in the
      others. Thirty four patients were followed during an average time of 31.2 months
      (range 18 to 50 months), amomg them 22 patients were treated with routine
      procedures and 12 were treated with additional syndesmosis surgical exploration.
      RESULTS: All the fractures were reunited in an average time of 13.1 weeks (range
      10 to 18 weeks) and full weight bearing began. The mean ankle and hindfoot scale
      of the American Orthopaedic Foot and Ankle Society (AOFAS) score was 79.86(range
      65 to 98) in the routine procedures group and 86.67 (range 78 to 100) in the
      syndesmosis exploration group and Olerud-Molander score was 77.27 (range 55 to
      100) and 86.67 (range 75 to 100) respectively. Statistically significant
      difference was found between the two groups (P<0.05). CONCLUSION: Syndesmosis
      surgical exploration is an essential treatment in some Weber type C ankle
      injuries, which make debridement and direct reduction of the syndesmosis
      possible, providing thus a more stabilized ankle joint. Level of Evidence III,
      Retrospective Comparative Study.

PMID- 24453654
TI  - Energy expenditure during gait in patients with mucopolysaccharidosis.
AB  - OBJECTIVE: The aim of this study is to evaluate energy expenditure in gait by
      mucopolysaccharidosis affected patients by means of a simple and adequate to the
      clinical environment methodology. METHODS: A cross-sectional study was carried
      out comparing energy expenditure during gait in 19 patients suffering from
      mucopolysaccharidosis (MPS Group) with 19 asymptomatic control individuals
      (Control Group). Energy expenditure was measured in calories (cal) using a Polar
      telemetric watch (model FT7) during a 50 meter walk. Variables such as age,
      weight, height, body mass index (BMI), initial hart rate, final hart rate, and
      walking time, were recorded. RESULTS: MPS Group showed a mean energy expenditure
      during gait of 2.84 cal (+/-1,01), versus 1.42 cal (+/-0,51), 100% higher than
      the Control Group; MPS also presented increased initial hart rate (22% higher),
      final hart rate (13% higher) and walking time (13% higher). CONCLUSIONS: Energy
      expenditure during gait in MPS patients was two times higher than control
      individuals; the methodology used showed to be a promising alternative, also
      adequate to the standard clinical environment. Level of Evidence III, Cross
      sectional Comparative Study.

PMID- 24453655
TI  - Current concepts in osteoarthritis.
AB  - Osteoarthritis (OA), the most common form of joint disease, affects mainly the
      hips, knees, hands and feet, leading to severe disability and loss of quality of
      life, particularly in the elderly population. Its importance grows every year
      with the aging of the population, with a large increase in the elderly population
      compared to younger patients. The progressive understanding of the
      pathophysiology of OA, the perception that the process is not purely mechanical
      and / or aging, and clarification of the inflammatory pathways involved led
      recently to the clinical application of various drugs and other measures. This
      update aims to expose the current concepts on the pathophysiology and treatment
      of OA. 

PMID- 24453656
TI  - Relationship between lumbar changes and modifications in the plantar arch in
      women with low back pain.
AB  - OBJECTIVE: : Evaluate the probable relationship among plantar arch, lumbar
      curvature, and low back pain. METHODS: : Fifteen healthy women were assessed
      taking in account personal data and anthropometric measurements, photopodoscopic
      evaluation of the plantar arch, and biophotogrammetric postural analysis of the
      patient (both using the SAPO software), as well as evaluation of lumbar pain
      using a Visual Analog Scale (VAS). The average age of the participants was 30.45
      (+/-6.25) years. RESULTS: : Of the feet evaluated, there were six individuals
      with flat feet, five with high arch, and four with normal feet. All reported
      algic syndrome in the lumbar spine, with the highest VAS values for the
      volunteers with high arch. Correlation was observed between the plantar arch and
      the angle of the lumbar spine (r = -0.71, p = 0.004) CONCLUSION: High arch was
      correlated with more intense algic syndrome, while there was moderate positive
      correlation between flat foot and increased lumbar curvature, and between high
      arch and lumbar correction. Level of Evidence IV. Case Series .

PMID- 24453657
TI  - Arthroscopic latarjet procedure: safety evaluation in cadavers.
AB  - OBJECTIVE: To evaluate the safety of arthroscopic Latarjet procedure in cadavers.
      METHODS: : Twelve cadaveric shoulders underwent arthroscopic Latarjet procedure
      in our laboratory for arthroscopy, by four different surgeons. Following surgery,
      the specimens were subjected to radiographic examination and evaluated by an
      independent examiner. Nineteen parameters were evaluated, including the coracoid
      graft fixation, positioning and angulation of the screws, neurological damage and
      integrity of tendons. RESULTS: : Four procedures were considered to be
      satisfactory, with no difference among the surgeons. The mean angulation of the
      screws was 27.2 degrees . The subscapularis splitting was, on average, 17.8mm
      from the upper edge. The coracoid graft was properly positioned relative to
      equator of the glenoid in 11 cases. There was no injury to the axillary or
      musculocutaneous nerves. The main complications were: interposition of soft
      tissue, suprascapular nerve injury, articular deviation of the graft, diastasis
      and conjoined tendon injury. CONCLUSION: : The arthroscopic Latarjet procedure is
      a complex technique in which each step must be precise to reduce the risk of
      complications. Our study showed a high risk of failure of the procedure. Level of
      Evidence IV, Case Series .

PMID- 24453658
TI  - Extracellular matrix remodeling in experimental intervertebral disc degeneration.
AB  - OBJECTIVE: To evaluate the remodeling of the extracellular matrix in
      intervertebral disc degeneration through the experimental model of intervertebral
      disc degeneration. METHODS: The model of disc degeneration induction, using
      needle 20G and 360 degrees  rotation, was applied for 30 seconds between the
      6(th)/7(th), and 8(th)/9(th) coccygeal vertebrae of Wistar rats. The intermediary
      level, between the 7(th) and 8(th) vertebrae, was taken as control, not being
      subjected puncture. The distribution of the extracellular matrix components
      involved in the remodeling and inflammation process, such as proteoglycans
      (aggrecan, decorin, biglycan), growth factors (TGFbeta), heparanase isoforms
      (HPSE1, HPSE2), metaloprotesasis-9 (MMP9) and interleukins (IL-6, IL-10) was
      analyzed during the post-injury period (15 to 30 days) and in the control group
      (discs collected immediately after the puncture, day zero). On the 15(th) day,
      acute phase of the disease, a reduced expression of extracellular matrix
      components had been observed, whilst there were no differences in the
      interleukins expression. At 30 days, the molecules followed a very similar
      pattern of expression in the control group (not affected by disc degeneration).
      RESULTS: The results show that during the acute phase significant alterations in
      the extracellular matrix components occur and in the late phase intervertebral
      disc returns to a profile similar to noninvolved tissue, probably due to
      extensive remodeling process of the extracellular matrix that is capable of
      regenerating the damaged tissue. CONCLUSION: : The experimental model used
      demonstrated the occurrence of significant changes in the extracellular matrix
      during the period analyzed after induction of intervertebral disc degeneration.
      Laboratory investigation.

PMID- 24453659
TI  - Pelvic reconstruction with allogeneic bone graft after tumor resection.
AB  - OBJECTIVES: : Pelvic reconstruction after tumor resection is challenging.
      METHODS: A retrospective study had been preformed to compare the outcomes among
      patients who received pelvic reconstructive surgery with allogeneic bone graft
      after en bloc resection of pelvic tumors and patients who received en bloc
      resection only. RESULTS: Patients without reconstruction had significantly lower
      functional scores at 3 months (10 vs. 15, P = 0.001) and 6 months after surgery
      (18.5 vs. 22, P = 0.0024), a shorter duration of hospitalization (16 day vs. 40
      days, P < 0.001), and lower hospitalization costs (97,500 vs. 193,000 RMB, P <
      0.001) than those who received pelvic reconstruction. Functional scores were
      similar at 12 months after surgery (21.5 vs. 23, P = 0.365) with no difference in
      the rate of complications between the two groups (P > 0.05). CONCLUSIONS: :
      Pelvic reconstruction with allogeneic bone graft after surgical management of
      pelvic tumors is associated with satisfactory surgical and functional outcomes.
      Further clinical studies are required to explore how to select the best
      reconstruction method. Level of Evidence IV, Case Series.

PMID- 24453660
TI  - The effects of exertion on the postural stability in young soccer players.
AB  - OBJECTIVE: : Analyze the effects of physical exertion during a soccer match on
      the functional capacity and stability of the lower limbs of young soccer players.
      METHODS: : We analyzed 10 soccer players who underwent functional capacity
      assessment of the lower limbs by a Hop Test protocol and evaluation of the level
      of postural stability in the Biodex Stability System (Biodex, Inc., Shirley, NY)
      before and immediately after a friendly game lasting 45 minutes. RESULTS: : After
      the match, there was a decrease in overall stability index (F(1,23) = 7.29 P =
      .024) and anterior posterior index (APSI) (F(1,23) = 5.53 P = .043). Fatigue in
      the dominant limb was responsible for the significant deficit in OSI (F(1,23) =
      3.16, P = .047) and APSI (F(1,23) = 3:49, P = .029), while the non-dominant limb
      did not cause any change in the pre and post-game. CONCLUSION: : A football match
      can cause decreased stability and functional capacity of the lower limbs in young
      players. Level of Evidence III, Pre-test and Post-test Study (Case-control) .

PMID- 24453661
TI  - Epidemiological study of cauda equina syndrome.
AB  - OBJECTIVE: : The primary purpose of this study was to determine the
      characteristics and outcomes of the patients admitted at our clinics diagnosed
      with cauda equina syndrome (CES). Secondarily, this study will serve as a basis
      for other comparative studies aiming at a better understanding of this condition
      and its epidemiology. METHODS: : We conducted a retrospective study by reviewing
      the medical records of patients diagnosed with CES and neurogenic bladder between
      2005 and 2011. The following variables were analyzed: gender, age, etiology,
      topographic level of the lesion, time between disease onset and diagnosis,
      presence of neurogenic bladder, time between diagnosis and surgery, neurological
      damage and neurogenic bladder persistence. RESULTS: : Considering that CES is a
      rare condition, we were not able to establish statistic correlation between the
      analyzed variables and the outcomes of the disease. However, this study brought
      to light the inadequacy of our public health system in treating that kind of
      patient. CONCLUSION: : The study shows that despite the well-defined basis for
      managing CES, we noted a greater number of patients with sequels caused by this
      condition, than is seen in the literature. The delayed diagnosis and,
      consequently, delayed treatment, were the main causes for the results observed.
      Level of Evidence IV, Case Series .

PMID- 24453662
TI  - Influence of slope on subtalar pronation in submaximal running performance.
AB  - OBJECTIVE: : To investigate the slope influence on the maximal subtalar pronation
      in submaximal running speeds. METHODS: : Sixteen endurance runners participated
      of a running economy (RE) test in a treadmill with different slopes (+1%, +5%,
      +10%, +15%). For each slope a 4-minute run was performed with no rest break for
      the purpose of measuring the magnitude of kinematic variables by means of a high
      frequency video camera positioned in a frontal-posterior plane of the individual.
      RESULTS: : No significant differences were verified in maximal subtalar pronation
      between legs and between the slopes adopted, showing that changes of running
      technique due to modifications of slope aren't enough to modify the behavior of
      maximum subtalar pronation. CONCLUSION: : The subtalar pronation is independent
      of slope, which may be influenced by other intervening variables. Level of
      Evidence II, Diagnostic Study.

PMID- 24453663
TI  - Evaluation of patients undergoing rotator cuff suture with the modified mason
      allen technique.
AB  - OBJECTIVE: : The purpose of this study was to clinically evaluate patients who
      underwent Arthroscopic Rotator Cuff Repair (RC) using the Modified Manson-Allen
      technique. METHODS: : We evaluated 79 patients who underwent shoulder
      arthroscopy. The lesions were repaired using the modified Mason-Allen suture
      between 2003 and 2009, divided by Cofield classification and clinically evaluated
      by the scoring system of the University of Los Angeles (UCLA) in the pre- and
      postoperative periods. RESULTS: : The evaluation of lesion sizes showed 7 small
      lesions (<1cm), 55 average lesions (1-3cm) and 17 large lesions (3-5cm), and in
      this last group there were 5 reruptures and the patients were reoperated by the
      same technique. Comparing the pre (14.1) and postoperative (32.6) values by UCLA
      system there was a significant improvement of score (142.3%), regardless of
      lesion size. The modified Mason-Allen suture provided satisfactory clinical
      results, regardless of lesion size, similar to those found in literature. The
      rerupture rate was high in large lesions. New suture techniques have been
      developed with the aim of reducing the incidence of rerupture. CONCLUSION: : The
      modified Mason-Allen suture technique provided clinical improvement, regardless
      of lesion size. Level of Evidence IV, Cases Series .

PMID- 24453664
TI  - Polymorphism of the ace gene and the alpha-actinin-3 gene in adolescent
      idiopathic scoliosis.
AB  - OBJECTIVE: : The I/D polymorphism of angiotensin-converting enzyme (ACE) and
      R577X of the alpha-actinin-3 (ACTN3) is related to changes in skeletal muscle
      function. The aim of this study was to evaluate the distribution of these
      polymorphisms in a family with multiple members with adolescent idiopathic
      scoliosis (AIS). METHODS: : Evaluated 25 subjects from a family with multiple
      members with AIS, by collecting 10mL of blood for DNA isolation. The genotyping
      of the I/D polymorphism of the ACE gene and the R577X of the ACTN3 gene was
      performed using two specific primers to classify individuals as homozygous or
      heterozygous. RESULTS: : Regarding the ACE polymorphism it was found that 19
      (76%) subjects were DD and 6 (24%) ID. The prevalence of the D allele was 88% and
      the I allele was 12%. Regarding the ACTN3 polymorphism there were 6 subjects RR
      (24%), 11 RX (44%) and 8 XX (32%). The prevalence of the R allele was 23 (46%)
      and the X allele was 27 (54%). CONCLUSION: : There was a difference between the
      distribution of the polymorphism of ACE and ACTN3 in the family studied. When
      assessing the ACE polymorphism a higher prevalence of the D allele was observed
      as compared with the I allele. Level of Evidence III, Cross-sectional, Clinical
      Trial.

PMID- 24453665
TI  - Physical therapy in the postoperative of proximal femur fracture in elderly.
      Literature review.
AB  - The proximal femoral fracture in the elderly is a serious public health problem.
      Surgical treatment of this fracture is used to reduce morbidity, together with
      postoperative physical therapy. The objective was to conduct a systematic review
      of physical therapy protocols in postoperative for fractures of the proximal
      femur in elderly. We selected randomized controlled trials in elderly in the past
      10 years, in Portuguese and English. There were 14 articles in the literature.
      Physical therapy has an important role in functional recovery of the elderly.
      Level of Evidence I, Systematic Review RCTs (Study results were homogenous). 

PMID- 24453666
TI  - Orthopedics nursing patients' profile of a public hospital in Salvador-Bahia.
AB  - OBJECTIVES: To describe the profile of patients treated in the trauma and
      orthopedics nursing of a trauma care referral public hospital of in the state of
      Bahia. METHODS: Cross-sectional study in which data were collected from medical
      records of patients in the period from July to December 2008. RESULTS: The
      profile of the patients involved was formed by subjects mostly male young
      subjects, victims of trauma from accidents, especially those with motorcycles or
      car runover. On the other hand,the most frequent traumas associated with urban
      violence were perforations by gunshot and stab wounds. The primary injury
      presented by these individuals was exposed fracture of the femur and the most
      common treatment was external fixation. The most frequent in-hospital
      complication was wound infection, which required another surgical approach. Most
      inpatients were discharged and only one death was reported during this period.
      CONCLUSION: The results of this study corroborate those from other institutions
      in the country, which may contribute to elaborate public policies for accidents
      and violence prevention. Level of Evidence IV, Case Series.

PMID- 24453667
TI  - Tomographic correlation of the Magerl technique for C1-C2 arthrodesis in
      rheumatoid arthritis.
AB  - OBJECTIVE: To use the tomographic analysis of C1 and C2 vertebrae to assess the
      possibility of using Magerl's technique in patients with rheumatoid arthritis.
      Other objectives were to obtain anatomical data for the choice of the surgical
      technique in general, to establish safety parameters and obtain epidemiological
      data of the population in question. METHODS: We retrospectively reviewed the CT
      scans of 20 patients with rheumatoid arthritis of the Outpatient Spine Group, IOT
      HCFMUSP. Data were analyzed statistically to obtain the mean values and the
      variance of each measurement: the length of the C2 pedicle to the C1 lateral
      mass, the thickness of the pedicle and the angle of attack of the screw in the
      isthmus of C2 to the horizontal. RESULTS: THE MEAN VALUES WERE, RESPECTIVELY:
      right 23.08 mm and left 23.16 mm, right 6.46 mm and left 6.50 mm, right 44.50(o)
      and left 44.95(o). DISCUSSION: The leading screw's manufacturers have implants
      compatible with the anatomical measurements found in this work. Considering the
      wide diffusion and mastery of Magerl's technique in our country and around the
      world, this is a safe surgical option that provides mechanical stability.
      CONCLUSION: Magerl's technique, according to tomographic analysis, can be used in
      patients with rheumatoid arthritis. Levels of Evidence IV,Case Series.

PMID- 24453668
TI  - Contribution of the evaluation of the clinical signals in patients with
      patellofemoral pain syndrome.
AB  - OBJECTIVE: As patellofemoral pain syndrome (PFPS) is a common disorder
      characterized by multifactorial etiology and whose the most prevalent symptom is
      a diffuse pain, usually located on the retropatellar region, however, it also
      shows signs and symptoms that can be related as excessive subtalar pronation,
      external tibial torsion, patellar displacement alterations, painful range of
      motion of the knee, pain in the patellar borders, muscular tightness and changes
      in quadriceps angle (Q Angle), the objective of this work was to determine the
      frequency of these signs and symptoms associated to a previous knee pain
      questionnaire. METHODS: Thirty-nine sedentary female volunteers had been
      evaluated, divided in two groups, PFPS (19) and Control (20). These subjects were
      evaluated for signs and symptoms described above, in addition to pain assessment
      by questionnaire. RESULTS: The results demonstrated a high frequency of pain in
      six of the thirteen questions in relation to the control group. CONCLUSION:
      According to these findings, we conclude that the functional evaluation of
      individuals with PFPS should consist of a previous knee pain questionnaire and an
      evaluation of the characteristic signs and symptoms for examination of the entire
      lower limb during static and functional situations. Level of Evidence II,
      Diagnostic Studies.

PMID- 24453669
TI  - Assessment of the quality of life through the SF-36 questionnaire in patients
      with chronic nonspecific low back pain.
AB  - The objective of this study was to evaluate the quality of life (QL) with the use
      of the SF-36 Questionnaire in patients with chronic nonspecific low back pain
      (CNLBP). Thirty patients with CNLBP were randomly assigned to one of three groups
      (Iso group (Isostretching), GPR group (Global Postural Reeducation), and the
      Iso+GPR group. Patients underwent physical therapy assessment with the use of the
      Vertebral Spine Assessment, the Visual Analog Scale of Pain (VASP), and the SF-36
      life quality questionnaire before the first session (first assessment), after
      three months of treatment (second assessment) and reassessed two months after the
      final session in the follow-up (third assessment). The results indicated that
      both physical therapy techniques reduced pain (p<0.001); when the techniques
      (Iso+GPR) were combined, the reduction in pain was significantly greater; and, in
      the follow-up assessment, the GPR method was more efficient. As for the QL,
      physical therapy techniques were effective after the interventions (p<0.001), and
      the Iso method was more effective when patients were reassessed in the follow-up.
      We conclude that the physical therapy techniques used in this study were
      efficient to treat CNLBP in the patients since they reduced pain and increased QL
      according to the results of the SF-36 questionnaire. Level of Evidence II,
      Randomized Controlled Clinical Trial. 

PMID- 24453670
TI  - Static evaluation of scapular positioning in healthy individuals.
AB  - OBJECTIVE: Evaluate the static positioning of the scapula on the rib cage in
      healthy subjects by means of clinical and radiographic evaluation to assess inter
      examiner reliability of clinical examination and verify the reliability of this
      evaluation method compared to the radiographic examination. METHODS: We selected
      30 adult individuals of both sexes with no diagnosis of shoulder pathology. The
      static clinical examination, following the protocol suggested by Burkhart et al,
      was performed repeatedly by two independent examiners, followed by the
      radiographic examination, which was later examined by the first evaluator.
      RESULTS: 73.3% of the subjects showed positioning of the scapula considered
      normal. The inter-examiner reliability and that of the clinical examination in
      relation to radiography were considered low and very low, respectively.
      CONCLUSION: The reproducibility of the evaluation performed by Burkhart was
      considered satisfactory to good, while the inter-examiner reproducibility of the
      clinical examination and the static reproducibility of the clinical examination
      with radiography were considered poor to satisfactory. Level of Evidence III,
      Study of Nonconsecutive Patients.

PMID- 24453671
TI  - Analysis of injuries' prevalence in surfers from Parana seacoast.
AB  - OBJECTIVE: to analyze the prevalence of musculoskeletal injuries of surfers from
      the Parana's seacoast. METHODS: Sixty men (27 +/- 6 years) completed a surf semi
      structured questionnaire (category, time of daily practice, frequency and
      exercises performed before and/or after surfing) and characteristics of injuries
      induced by this sport. A descriptive analysis of the data on distribution of the
      relative frequency was performed. RESULTS: It was found that 70% of the
      respondents practiced surfing as a relaxing activity, 28% were amateurs and 2%
      were professionals, who were surfing for 10 years or more. Most of them surfed
      between 2 to 4 times a week during 2 to 4 hours a day. The most common exercise
      performed before surfing was upper and lower limbs stretching and no exercises at
      all was done after practice. The most common injury was contusion (29%), lower
      limb was the most affected segment (46%) and the most common cause of injury was
      due to contact with the board (52%). The interruption period mostly reported was
      1-3 months and the most frequent treatment was taking medicines. CONCLUSIONS:
      Recreational was the predominant category of surfers with lower limb's contusion
      as the most common musculoskeletal injury, resulting from contact with the board,
      being treated with medication and rest. Level of Evidence II, Retrospective
      Study.

PMID- 24453672
TI  - Rotation flaps for coverage after total knee arthroplasty.
AB  - OBJECTIVE: To evaluate the results obtained using local myocutaneous rotation
      flaps in cases of wound dehiscence after total knee arthroplasty. METHODS:
      Patients undergoing these surgical procedures were selected in the 2000-2012
      period. The nine selected cases during this period were subjected to flap
      coverage due to skin dehiscence associated with infection. In eight cases we used
      rotation flaps of the medial gastrocnemius, and in one case we used advancing
      skin. RESULTS: Eighty nine percent of the cases were successful in the coverage
      of the prosthesis and the viability of the flaps. In four cases it was possible
      to maintain or review the prosthesis. Four other cases progressed to amputation
      due to failure on treatment of infections, and one case remained without the
      prosthesis. The functional evaluation showed an unsatisfactory outcome in 89% of
      cases. CONCLUSION: Coverage flaps are a good option for the treatment of cases of
      dehiscence with exposure of the prosthesis and the functional failure was
      associated with the inability to control the infection and the damage it caused.
      Level of Evidence IV, Case Series.

PMID- 24453673
TI  - Epidemiology of adolescent idiopathic scoliosis in students of the public schools
      in Goiania-GO.
AB  - OBJECTIVE: To investigate the prevalence of adolescent idiopathic scoliosis in
      school children from 10 to 14 years in public schools in Goiania, GO, Brazil.
      METHODS: In a cross-sectional study, 476 students were randomly selected from 5
      public schools, from a total of 33,343 students distributed in 162 schools. These
      subjects received the informed consent prior, which was returned after being
      signed by parents on physical examination day. We evaluated the symmetry of the
      shoulders, the scapulae, the triangle-cut, the hip evenness and the Adams test.
      In suspected cases, students were referred to panoramic radiographs of the spine.
      RESULTS: 418 students participated in the study (adjusted sampling error of
      3.2%). Of this total, 31 students were suspected of scoliosis (17 males and 14
      females). Twenty-eight students took radiographs, of which 18 were diagnosed with
      adolescent idiopathic scoliosis (11 female and 7 male), determining the
      prevalence of 4.3%. The chi-square test suggested no statistical difference in
      prevalence between the sexes. One student had congenital scoliosis. CONCLUSION:
      The prevalence of adolescent idiopathic scoliosis in the public schools of
      Goiania is 4.3%. Level of Evidence III, Study of Nonconsecutive Patients.

PMID- 24453674
TI  - Clinical outcomes of surgical treatment for talar malunions and nonunions.
AB  - OBJECTIVE: To present our experiences of treating talar malunions and nonunions.
      METHOD: Between January 2000 and September 2009, 26 patients with malunions or
      nonunions after talar fractures underwent surgical treatment according to
      different types of talar deformities. The treatment outcomes were evaluated using
      AOFAS ankle-hindfoot scale as well as plain radiographs. RESULTS: 20 patients
      were available for follow-up for 30 (range, 24 to 60) months. No wound healing
      problems or infections occurred and solid unions were achieved in all patients.
      Radiological unions were achieved at a mean time of 14 (range, 12 to 18) weeks.
      The mean time to complete weight-bearing was 16 (range, 14 to 20) weeks. The mean
      AOFAS score increased significantly from 36.2 (range, 27 to 43) to 85.8 (range,
      74 to 98). CONCLUSION: Surgical interventions for malunions and nonunions after
      talar fractures can bring about satisfactory outcomes, and the appropriate
      procedure should be adopted according to different types of posttraumatic
      deformities. LEVEL OF EVIDENCE: IV, Retrospective Study.

PMID- 24453675
TI  - Immunohistochemical expression of vegf and her-2 proteins in osteosarcoma
      biopsies.
AB  - OBJECTIVES: To identify the prevalence of erbB-2 and vascular endothelial growth
      factor (VEGF) in osteosarcoma biopsies and to correlate them with possible
      prognosis factors. METHODS: Retrospective study conducted at the Hospital do
      Cancer de Barretos-SP including 27 osteosarcoma biopsies immunohistochemically
      stained for VEGF and erbB-2. The pathological characteristics were collected from
      medical records of patients to correlate with markers. RESULTS: In 27 biopsies,
      four overexpressed VEGF and three overexpressed erbB-2. Two thirds of patients
      had no metastases. Almost all patients with overexpression of VEGF showed
      metastases. Overexpression of erbB-2 was inversely related to the presence of
      metastases. There was no significant association between markers and prognosis.
      CONCLUSION: We identified a low prevalence of erbB-2 and VEGF in the sample.
      There was no significant association between overexpression of markers and
      pathological features. A larger sample and a longer follow-up, in addition to
      using new laboratory techniques can determine the real expression of VEGF and
      erbB-2 and its role in osteosarcoma . Level of Evidence III, Case-Control Study.

PMID- 24453676
TI  - Static load test of the modified sliding hip screw: the DHS-AF(r).
AB  - OBJECTIVE: To analyze the in vitro mechanical strength of the DHS-AF((r)).
      METHODS: We evaluated the in vitro resistance of a sliding bolt modified by the
      addition of a connector system, DHS-AF((r)). RESULTS: The changes performed by
      the authors allow the exchange by the surgeon of the sliding bolt without the
      need to remove the plate and disassemble the entire device to reposition it
      properly. We conducted a static bending test to evaluate maximum strength,
      stiffness and ductility of the system. DHS-AF((r)) showed satisfactory mechanical
      properties when compared to other conventional devices which use the same
      principle. CONCLUSION: Based on these results, the authors propose the use of
      this new implant in further in vivo studies. Level of Evidence III, Analytical
      Study.

PMID- 24453677
TI  - Tomographic correlation for Magerl's technique in C1-C2 arthrodesis in children.
AB  - OBJECTIVE: To analyze through tomographic studies, the morphology and dimensions
      of the C1-C2 vertebrae in pediatric patients, to evaluate the possibility of
      application of Magerl's technique in these patients, and to contribute with data
      for the usage of the technique in safety. METHOD: Forty normal cervical
      tomographies, from patients at an age range of 24-120 months of age and from both
      genders, were retrospectively analyzed. Data was statistically analyzed to obtain
      mean value and variations of each measurement: length from the C2's pedicle to
      C1's lateral mass, thickness of the pedicle of C2, the attack angle of the screw
      at the C2 isthmus with the horizontal axis and the distance from the odontoid to
      the anterior arch of C1. RESULTS: THE MEAN VALUES OBTAINED WERE: length right
      30.86 mm, left 31.47 mm; thickness right 5.28 mm, left 5.26 mm; attack angle
      right 46.25(0) , left 44.50(0) ; distance from odontoid to anterior arch of C1
      2,17 mm. CONCLUSION: The Magerl technique, after tomographic study, seems to be a
      viable option to be used in pediatric patients. Level of Evidence IV, Case
      Series.

PMID- 24453678
TI  - How does static stretching influence the tendons mechanical response?
AB  - OBJECTIVE: Analyze in vitro the mechanical response of bovine calcaneus tendons
      subjected to static stretching in three different intervals (15, 30, 45 s).
      METHODS: Six groups of bovine calcaneus tendons (n=10) were formed according to
      the static stretching protocol: three different intervals (15, 30, 45 s) and
      initial stretching percentage (2.5% and 3.5%). The control group (n=10) did not
      perform prior stretching. At the end of the stretching tests, the specimens were
      subjected to stress rupture tests. RESULTS: The values for force relaxation
      presented stability after the 30(th) second (p<0.0001) at both levels of
      deformation. Greater force relaxation (p<0.0026) and the least tensile strength
      (p=0.0123) was observed in the group that was subjected to the highest stretch
      percentage (3.5%). No difference was observed between the rupture parameters of
      the stretch and control groups. The variables, stretch duration and percentage
      did not demonstrate interaction. CONCLUSION: In relation to force relaxation, the
      30 second interval seems to be the most effective when stretching tendons. This
      fact should be considered when establishing new clinical stretching protocols.
      Laboratory investigation.

PMID- 24453679
TI  - Relevance of infiltration analgesia in pain relief after total knee arthroplasty.
AB  - OBJECTIVE: The aim of the study was to assess the effect of different types of
      anesthesia on pain intensity in early postoperative period. PATIENTS AND METHODS:
      A total of 87 patients (77 women, 10 men) scheduled for total knee arthroplasty
      (TKA) were assigned to receive either subarachnoid anesthesia alone or in
      combination with local soft tissue anesthesia, local soft tissue anesthesia and
      femoral nerve block and pre-emptive infiltration together with local soft tissue
      anesthesia. We assessed the pain intensity, opioid consumption, knee joint
      mobility, and complications of surgery. RESULTS: Subjects with pre-emptive
      infiltration and local soft tissue anesthesia had lower pain intensity on the
      first postoperative day compared to those with soft tissue anesthesia and femoral
      nerve block (P=0.012, effect size 0.68). Subjects who received pre-emptive
      infiltration and local soft-tissue anesthesia had the greatest range of motion in
      the operated knee at discharge (mean 90 grades [SD 7], P=0.01 compared to those
      who received subarachnoid anesthesia alone, and P=0.001 compared to those with
      subarachnoid together with soft tissue anesthesia). CONCLUSION: Despite the
      differences in postoperative pain and knee mobility, the results obtained
      throughout the postoperative period do not enable us to favour neither local nor
      regional infiltration anesthesia in TKA. Level of Evidence II, Prospective
      Comparative Study.

PMID- 24453680
TI  - Effects of laser therapy in peripheral nerve regeneration.
AB  - OBJECTIVE: The influence of dose of low power lasertherapy (AsGaAl, 830 nm) on
      the regeneration of the fibular nerve of rats after a crush injury was evaluated
      by means of the functional gait analysis and histomorphometric parameters.
      METHODS: Controlled crush injury of the right common fibular nerve, immediately
      followed by increasing doses (G1: no irradiation; G2: simulated; G3: 5 J/cm(2);
      G4: 10 J/cm(2); G5: 20 J/cm(2)) laser irradiation directly on the lesion site for
      21 consecutive days. Functional gait analysis was carried out at weekly intervals
      by measuring the peroneal/fibular functional index (PFI). The animals were killed
      on the 21(st) postoperative day for removal of the fibular nerve, which was
      prepared for the histomorphometric analysis. RESULTS: The PFI progressively
      increased during the observation period in all groups, without significant
      differences between them (p>0.05). The transverse nerve area was significantly
      wider in group 2 than in groups 3 and 4, while fiber density was significantly
      greater in group 4 than in all remaining groups. CONCLUSION: The low power AsGaAl
      laser irradiation did not accelerate nerve recovery with any of the doses used.
      Level of Evidence I, Therapeutic Studies Investigating the Results of Treatment.

PMID- 24453681
TI  - Prospective randomized clinical trial: single and weekly viscosupplementation.
AB  - OBJECTIVE: To compare two different dosages of an intermediate molecular weight
      sodium hyaluronate (HA) (Osteonil((r))-TRB Pharma) assessing whether a single 6
      ml application of this HA has the same effectiveness as the classical three
      weekly 2 ml dose. METHODS: 108 patients with knee osteoarthritis were randomized
      into two groups of 54 patients each. The groups were designated "single" (S) and
      "weekly" (W). Patients in group S underwent a viscosupplementation procedure by
      application of only 6 ml of sodium hyaluronate and 1 ml triamcinolone
      hexacetonide. Patients in group W underwent the procedure of viscosupplementation
      through three applications with 2 ml sodium hyaluronate with a week interval
      between them, and the first application was also performed with the infiltration
      of 1 ml (20 mg) of Triamcinolone Hexacetonide. Both groups were assessed before,
      at one month and three months after application, by responding to the WOMAC,
      Lequesne, IKDC and VAS questionnaires. RESULTS: There was no statistical
      difference between the single application of 6 ml of sodium hyaluronate and
      classic application with three weekly injections. However, only the classical
      regime showed statistically significant improvement in baseline pain (WOMAC pain
      and VAS). CONCLUSION: Our results suggest that both application schemes improve
      application function, but the three-weekly regimen of 2 ml was more effective in
      reducing pain. Level of Evidence I, Prospective Randomized, Clinical Trial.

PMID- 24453682
TI  - Surgical treatment of the late - presenting developmental dislocation of the hip
      after walking age.
AB  - OBJECTIVE: Cases of developmental dislocation of the hip (DDH) still occur after
      walking age because of late or missed diagnosis and failed conservative
      treatment. The choice of treatment for DDH after walking age continues to be
      controversial, and one of the options is open reduction combined with innominate
      osteotomy. METHODS: Twenty patients with 26 surgically treated hips with DDH,
      were evaluated from 2005 to 2008, using innominate osteotomy by Salter's
      technique after open reduction and capsulorraphy. The age of patients, fifteen
      females and five males, at time of surgery ranged from 12 to 18 months (mean age
      14.7 months). Six patients had bilateral dislocation and in the remaining, nine
      had their left hip dislocated and five had their right hip dislocated. RESULTS:
      The results were evaluated according to modified McKay criteria and to Severin
      radiological criteria, after a mean follow-up of 46.7 months. Eighty - nine
      percent of hips were rated as excellent or good by McKay criteria. There were no
      poor results. According to Severin criteria, 77% were type I and II while 23%
      showed type III and IV, no hips were rated as Severin's group V or VI. There was
      one case (3.8%) of re-dislocation, but revision surgery resulted in stable,
      concentric, and permanent reduction. No cases of infection, graft fracture and
      vascular or nervous injury were reported. CONCLUSION: Open reduction combined
      with Salter osteotomy does not hurt the hip with regard to acetabular remodeling
      for children between 12 and 18 months of age. Level of Evidence IV, Case Series.

PMID- 24453683
TI  - Analysis of scientific articles published in two general orthopaedic journals.
AB  - OBJECTIVE: To give an overview of the behaviour and scientific contributions of
      the Journal of Bone and Joint Surgery American (JBJS-A) and British Volume (JBJS
      B). METHODS: 480 original articles published in 2009 were identified through a
      combined comprehensive computer and manual library search. Articles were assigned
      to 11 orthopaedic categories and by country, type and specialty of the
      institution. Possible grants and citations were analysed. USA led all countries
      in published articles (36,87%), followed by UK (20,62%) and South Korea (5,83%).
      Most studies published were performed at academic institutions (65,83 %), only
      4,16% at private practices. RESULTS: Almost half of the articles (46,24%) were
      published in three categories: hip (19.16%), knee (13.75%) and trauma (13.33%).
      In both journals 47.15% articles had at least one funding source. A review of
      articles published in major journals allows to show how research in orthopaedics
      is distributed worldwide. CONCLUSION: This study shows that a variety of
      different journals is neccessary to reflect the broad spectrum of orthopaedics in
      depth. Level of Evidence III, Retrospective Comparative Study.

PMID- 24453684
TI  - Publication rates of papers presented at the Brazilian Orthopedic Meeting.
AB  - OBJECTIVE: To quantify the publication rates of the papers presented at the 2007
      Brazilian Orthopedics Meeting (Congresso Brasileiro de Ortopedia - CBOT).
      METHODS: Evaluation of the proportion of abstracts submitted by the various
      orthopedic subspecialties and according to the Brazilian states. Then, a Lilacs
      and PubMed search was performed in order to determine which presentations
      generated national or international published papers. RESULTS: Sao Paulo and the
      Southeast region were responsible for the greatest number of presentations at the
      congress (54.1% and 68.3% respectively). Shoulder and Elbow were the subspecialty
      responsible for more presentations (13.8%). Among the 653 studies presented at
      the congress, 174 (26.6%) were published. Oral presentations obtained a
      publication rate 3.58 times higher than posters. CONCLUSION: The CBOT publication
      rate is lower than 30%. Many of the papers presented at the CBOT does not pass
      the scrutiny of scientific journals and therefore should not be the only source
      of scientific update of the participants: Descriptive Epidemiologic.

PMID- 24453686
TI  - In vitro effects of caffeine in growth cartilage of rats.
AB  - OBJECTIVE: To evaluate the in vitro effetcs of caffeine on proliferation,
      apoptosis a nd gene transcripts expression of chondrogenic differentiation in
      growth cartilage. METHODS: THE CARTILAGINOUS EPIPHYSES OF FEMURS OF NEWBORN RATS,
      WHICH WERE DIVIDED INTO TWO SUBGROUPS: treated with caffeine and control group,
      both observed over the time periods of 0, 7, 14 and 21 days. The cartilaginous
      epiphyses of femurs of each subgroup and each time span were subjected to
      histomorphometric, immunohistochemical analysis, Tunel technique and RT-PCR in
      real time. RESULTS: The decrease in proliferative activity and the increase of
      apoptotic chondroblasts at 21 days were found regardless of the subgroup.
      However, the decrease in cell proliferation caused by caffeine was lower than in
      the control group and significantly increased the expression of gene transcripts
      for chondrogenic differentiation, represented by Sox-9 and Runx-2. However, the
      in vitro culture with caffeine revealed antagonistic effects: despite the
      positive effect on chondroblasts proliferation and differentiation, caffeine
      increased apoptosis, characterized by increased expression of caspase 3 and of
      the number of cells undergoing apoptosis (p<0.05). CONCLUSION: Caffeine presents
      antagonistic effects in vitro on growth cartilage, increasing the proliferation,
      differentiation and cell apoptosis. Experimental Study .

PMID- 24453685
TI  - Translation into Portuguese of questionnaires to assess knee injuries.
AB  - The aim of this systematic review was to review the quality of the translation
      and the measurement properties from questionnaires that assess injuries of the
      knee. We included questionnaires that were developed in foreign language and have
      been translated and validated into Portuguese. The databases used were CINAHL,
      SPORTDiscus, LILACS, PUBMED and SCIELO and the final search resulted in a total
      of 868 studies included, from which 16 were eligible. Most included
      questionnaires presented all steps expected in a translation process; however
      there were some deficiencies in measurement properties among the questionnaires.
      The VISA-P Brazil was the best questionnaire when analyzing translation process
      and measurement properties tested. It was the only questionnaire that tested all
      measurement properties investigated and presented adequate values for all of
      them. KOS-ADLS was the best questionnaire translated to Portuguese from Portugal.
      Among all, the VISA-P Brazil is the best questionnaire to be used with Brazilian
      Portuguese speakers when the condition is related to patellar tendinopathy and
      the LEFS is the best questionnaire for other general conditions of the knee. For
      Portuguese from Portugal, the best questionnaire is the KOS-ADLS, and like the
      LEFS it does not target any specific injury. 

PMID- 24453687
TI  - Clinical assessment of spasticity in individuals with spinal cord injury.
AB  - OBJECTIVE: To evaluate the effect of neuromuscular electrical stimulation on
      spasticity in patients with spinal cord injury. METHODS: The study included
      eleven subjects with spinal cord injuries (C4 to T5). The modified Ashworth scale
      and pendulum test, which is accomplished through the Pendular Test Device - PTD
      (equipment which has a quartz crystal transducer accelerometer and optic fiber
      flexible electrogoniometer measuring the tensions and angular displacements).
      Patients underwent neuromuscular electrical stimulation (NMES) to the quadriceps
      muscle from fibular nerve, and the tests were administered before and after
      therapy. RESULTS: The data show a decrease in spasticity after NMES, with
      features such as increased variation between maximum and minimum peaks, i.e.
      increased amplitude of the curves. Furthermore, data from the subjective scale,
      and modified Ashworth scale after neuromuscular electrical stimulation also
      showed a reduction in the values of spasticity. CONCLUSION: The data suggest that
      NMES is effective in reducing spasticity immediately after completion. Level of
      Evidence II, Therapeutic Studies-Investigating the Results of Treatment .

PMID- 24453688
TI  - Extensor mechanism allograft in total knee arthroplasty.
AB  - OBJECTIVE: To analyze the experience with allograft transplantation of the
      extensor mechanism in total knee arthroplasty and compare results with the
      international experience. METHODS: We retrospectively evaluated three cases of
      extensor mechanism allograft after total knee arthroplasty performed in our
      hospital with the aid of one of the few tissue banks in Brazil and attempt to
      establish whether our experiences were similar to others reported in the world
      literature regarding patient indication, techniques, and outcomes. RESULTS: Two
      cases went well with the adopted procedure, and one case showed bad results and
      progressed to amputation. As shown in the literature, the adequate tension of the
      graft, appropriate tibial fixation and especially the adequate patient selection
      are the better predictors of good outcomes. Previous chronic infection can be an
      unfavorable predictor. CONCLUSION: This surgical procedure has precise
      indication, albeit uncommon, either because of the rarity of the problem or
      because of the low availability of allografts, due to the scarcity of tissue
      banks in Brazil. Level of Evidence IV, Case Series.

PMID- 24453689
TI  - Comparison of Floseal(r) and electrocautery in hemostasis after total knee
      arthroplasty.
AB  - OBJECTIVE: To evaluate whether hemostasis with eletrocauterization in comparison
      with Floseal((r)) leads to different bleeding rates during total knee
      arthroplasty. METHODS: A COMPARATIVE STUDY WAS PERFORMED BETWEEN TWO GROUPS:
      group with ten consecutive total knee arthroplasties with Floseal((r)) used as
      hemostatic method and control group with ten consecutive total knee
      arthroplasties with eletrocauterization as hemostatic method. Bleeding parameters
      such as debit of the drain, liquid infusion and blood transfusion rate were
      recorded. RESULTS: Floseal((r)) group received less blood transfusion, less
      liquid infusion and lower drainage in absolute numbers compared to the control
      group. However, no parameter was statistically significant. CONCLUSION:
      Hemostasis with Floseal((r)) is as effective as hemostasis with
      eletrocauterization, what makes it a viable alternative to patients with
      contraindication to electric scalpel use. Level of Evidence II, Prospective
      Comparative Study.

PMID- 24453690
TI  - Radiographic assessment of the femoral insertion of the posterior cruciate
      ligament.
AB  - OBJECTIVE: To establish the radiographic images of the femoral insertion of the
      posterior cruciate ligament (PCL), in order to assist the creation of anatomical
      femoral tunnels during surgeries, and to be used as parameters in postoperative
      evaluation of the location of these tunnels. METHODS: Thirty adult cadaver knees
      were used. The PCL anterolateral (AL) and posteromedial (PM) bundles' center was
      marked with a metallic marker. Radiographs were taken and a grid system was
      established to locate the position of bundles insertion. The percentile in which
      the projection of each bundle's center was in relation to the Blumensaat line was
      also determined. RESULTS: In the anteroposterior view, AL and PM bundles' centers
      were on average, on the 42.5% and 38.18% percentiles of Blumensaat's line,
      respectively. In lateral views, the AL and PM bundles' centers corresponded to
      the 72.94% and 55.56% percentiles of the line, respectively. In 73.33% of the
      knees the AL bundle center was on the 3D quadrant and in 70% of samples the PM
      bundle center was in quadrant 2D. CONCLUSIONS: We established an X-ray pattern of
      femoral insertion of PCL that may be of interest for intraoperative control,
      before tunnel drilling, and also for post-operative evaluation of tunnel
      location. Controlled Laboratory Study .

PMID- 24453691
TI  - Biomechanical adaptations of mice cortical bone submitted to three different
      exercise modalities.
AB  - OBJECTIVE: To compare the adaptive effects of three non-weight bearing exercise
      on bone mechanical properties. METHODS: 24 male Balb/c mice (22-25g), were
      randomly divided into four groups (n=6): sedentary group (S); swimming group (N)
      which performed sessions five times per week for 60 min progressively; resistance
      group (R), which performed climbing exercise with progressive load, three times
      per week; and combined group (C), which performed the same protocols
      aforementioned being three times a week according to N protocol and two times a
      week the R protocol during eight weeks. Biomechanical tests, load until failure
      and stiffness evaluation of shinbone was performed after animals have been
      sacrificed. RESULTS: Stiffness values were statistically higher only in the
      isolated modalities groups (N and R, 41.68 +/- 10.43 and 41.21 +/- 11.38 N/mm,
      respectively) compared with the S group (28.48 +/- 7.34 N/mm). However, taking
      into consideration the final body mass, relative values, there was no difference
      in the biomechanical tests among the groups. CONCLUSION: Data from the present
      investigation demonstrated a favorable influence of muscle contraction in lower
      impact isolated exercise modalities on absolute stiffness values, i.e.groups N
      and R, whereas the combined group (C) did not present any statistical significant
      difference compared to sedentary group. Level of Evidence II, Prospective
      Comparative Study .

PMID- 24453692
TI  - Congenital syndactyly: case by case analysis of 47 patients.
AB  - OBJECTIVE: To assess and report clinical data from patients with syndactyly.
      METHODS: A retrospective review of 47 patients treated between April 2002 and
      April 2012. RESULTS: Among the 47 analyzed patients, 33 (70%) were male and 14
      (30%) female. The total number of syndactylies was 116. The right hand was
      affected in 19 patients (40%), the left hand in 12 (24%) and 31 (36%) were
      bilaterally compromise. Sixteen patients (34%) also presented genetic syndromes.
      Among the 31 (66%) patients without syndromes, 12 (39%) had isolated syndactyly
      and 19 (61%) presented association with other hand anomalies. The third web space
      was affected 45 (39%) times; the fourth, 35 (30%) times; the second, 22 (19%)
      times and the first web space 14 (22%) times. Simple syndactyly was found 68
      (59%) times, complete syndactyly in 44 (65%) and incomplete in 24 (55%). Complex
      syndactyly was found 48 (41%) times. CONCLUSION: The results in this study are
      similar to the literature. Epidemiological Study .

PMID- 24453693
TI  - Bone age in cerebral palsy.
AB  - OBJECTIVE: To compare the chronological age and bone age among cerebral palsy
      patients in the outpatient clinic and its correlation with the type of
      neurological involvement, gender and functional status. METHODS: 401 patients
      with spastic cerebral palsy, and ages ranging from three months to 20 years old,
      submitted to radiological examination for bone age and analyzed by two
      independent observers according Greulich & Pyle. RESULTS: In the topographic
      distribution, there was a significant delay (p<0.005) in tetraparetic (17.7
      months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the
      hemiparetic group, the mean bone age in the affected side was 96.88 months and
      the uncompromised side was 101.13 months (p<0.005). Regarding functional status,
      the ambulatory group showed a delay of 18.73 months in bone age (p<0.005).
      Comparing bone age between genders, it was observed a greater delay in males
      (13.59 months) than in females (9.63 months), but not statistically significant
      (p = 0.54). CONCLUSION: There is a delay in bone age compared to chronological
      age influenced by the topography of spasticity, functional level and gender in
      patients with cerebral palsy. Level of Evidence IV, Case Series.

PMID- 24453694
TI  - Experimental model of osteoporosis: comparison between ovariectomy and botulinum
      toxin a.
AB  - OBJECTIVE: To evaluate whether Botulinum toxin-A (BTX-A) has a similar effect to
      that of ovariectomy (OVX) on bone regarding bone mineral densitometry. METHODS: A
      total of 51 female rats were randomly divided into three groups of 17 animals
      each. The rats in the first group formed the control group, without any surgical
      procedure (Group 1). Group 2 received BTX-A while Group 3 was subjected to OVX. A
      total of 8 IU of BTX-A was injected into the right femoral region of all rats in
      Group 2. At baseline and 14 weeks later, bone mineral densities (BMD) of the left
      and right femurs of all rats in both groups were measured. RESULTS: There was no
      statistically significant difference between the groups with respect to baseline
      BMD. At the 14(th) week the BMD of the right femurs were statistically
      significantly higher in Group 1 than other groups, although there was no
      statistically significant difference between Groups 2 and 3. The mean BMD results
      of the left femur in Group 3 were statistically significantly lower than the
      results in Groups 1 and 2 at the 14(th) week. CONCLUSION: The results of the
      current study showed that BTX-A had a similar effect to that of OVX on
      osteoporosis regarding BMD. Evidence Level I, Experimental, Controlled, Animal
      Study .

PMID- 24453695
TI  - Comparison of treatment results of acute and late injuries of the lisfranc joint.
AB  - OBJECTIVE: A retrospective comparison of treatment difficulties and treatment
      outcomes in Lisfranc joint injuries with late and early diagnosis. METHODS: The
      study group consisted of 10 patients diagnosed and treated properly within six
      months to 20 years of the accident causing the injury (mean six years). The
      control group consisted of the same number of randomly selected patients with a
      similar type of injury treated immediately after the accident. Mean follow-up was
      13 years in the study group and eight years in the control group. The analysis
      evaluated the causes of the delay and the foot function at the time of follow up,
      measured using the AOFAS Midfoot Scale and the Lublin Foot Functional Score. The
      scores of the patients were analyzed using the non-parametric Mann-Whitney U test
      and the non-parametric Wilcoxon test. RESULTS: The control group had
      statistically significantly better scores on both scales. CONCLUSION: The main
      cause of treatment delay was misdiagnosis by the primary care physician. Level of
      Evidence III, Retrospective Comparative Study .

PMID- 24453696
TI  - The Age Pattern of Increases in Mortality Affected by HIV: Bayesian Fit of the
      Heligman-Pollard Model to Data from the Agincourt HDSS Field Site in Rural
      Northeast South Africa.
AB  - BACKGROUND: We investigate the sex-age-specific changes in the mortality of a
      prospectively monitored rural population in South Africa. We quantify changes in
      the age pattern of mortality in a parsimonious way by estimating the eight
      parameters of the Heligman-Pollard (HP) model of age-specific mortality. In its
      traditional form this model is difficult to fit and does not account for
      uncertainty. OBJECTIVE: 1. To quantify changes in the sex-age pattern of
      mortality experienced by a population with endemic HIV. 2. To develop and
      demonstrate a robust Bayesian estimation method for the HP model that accounts
      for uncertainty. METHODS: Bayesian estimation methods are adapted to work with
      the HP model. Temporal changes in parameter values are related to changes in HIV
      prevalence. RESULTS: Over the period when the HIV epidemic in South Africa was
      growing, mortality in the population described by our data increased profoundly
      with losses of life expectancy of ~15 years for both males and females. The
      temporal changes in the HP parameters reflect in a parsimonious way the changes
      in the age pattern of mortality. We develop a robust Bayesian method to estimate
      the eight parameters of the HP model and thoroughly demonstrate it. CONCLUSIONS:
      Changes in mortality in South Africa over the past fifteen years have been
      profound. The HP model can be fit well using Bayesian methods, and the results
      can be useful in developing a parsimonious description of changes in the age
      pattern of mortality. COMMENTS: The motivating aim of this work is to develop new
      methods that can be useful in applying the HP eight-parameter model of age
      specific mortality. We have done this and chosen an interesting application to
      demonstrate the new methods.

PMID- 24453697
TI  - Archaeal production of polyhydroxyalkanoate (PHA) co- and terpolyesters from
      biodiesel industry-derived by-products.
AB  - The archaeon Haloferax mediterranei was selected for production of PHA co- and
      terpolyesters using inexpensive crude glycerol phase (CGP) from biodiesel
      production as carbon source. CGP was assessed by comparison with the application
      of pure glycerol. Applying pure glycerol, a copolyester with a molar fraction of
      3-hydroxybutyrate (3HB) of 0.90 mol/mol and 3-hydroxyvalerate (3HV) of 0.10
      mol/mol, was produced at a volumetric productivity of 0.12 g/Lh and an
      intracellular PHA content of 75.4 wt.-% in the sum of biomass protein plus PHA.
      Application of CGP resulted in the same polyester composition and volumetric
      productivity, indicating the feasibility of applying CGP as feedstock. Analysis
      of molar mass distribution revealed a weight average molar mass M w of 150 kDa
      and polydispersity P i of 2.1 for pure glycerol and 253 kDa and 2.7 for CGP,
      respectively; melting temperatures ranged between 130 and 140 degrees C in both
      setups. Supplying gamma -butyrolactone as 4-hydroxybutyrate (4HB) precursor
      resulted in a poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate-co-4
      hydroxybutyrate] (PHBHV4HB) terpolyester containing 3HV (0.12 mol/mol) and 4HB
      (0.05 mol/mol) in the poly[(R)-3-hydroxybutyrate] (PHB) matrix; in addition, this
      process runs without sterilization of the bioreactor. The terpolyester displayed
      reduced melting (melting endotherms at 122 and 137 degrees C) and glass
      transition temperature (2.5 degrees C), increased molar mass (391 kDa), and a
      polydispersity similar to the copolyesters. 

PMID- 24453699
TI  - Introduction: enhancing mobility in multiple sclerosis.

PMID- 24453698
TI  - The potent in vitro skin permeation of archaeosome made from lipids extracted of
      Sulfolobus acidocaldarius.
AB  - Archaeosomes are a new generation of liposomes that exhibit higher stabilities
      under different conditions, such as high temperatures, alkaline or acidic pH, and
      presence of bile salts in comparison with liposomes, and can be used in
      biotechnology including drug, gene, and vaccine delivery. The objective of this
      study was to prepare archaeosomes using lipid extracted from Sulfolobus
      acidocaldarius and evaluate their physicochemical properties. The lipids were
      extracted from S. acidocaldarius and assayed by High Performance Thin-Layer
      Chromatography (HPTLC). Archaeosomes were prepared using film method and
      methylene blue was used as drug model. They were characterized for their vesicle
      size and Differential Scanning Calorimetry (DSC) was used to investigate changes
      in their thermal behavior. The released amount of methylene blue was determined
      using a dialysis membrane and rat skin. HPTLC analysis of the extracted lipids
      showed that glycerol ether may be the major lipid with more than 78 percent
      probability. Results of particle size determination showed a mean size of 158.33
      nm and the results of DSC indicated the possible interaction of methylene blue
      with lipids during the preparation of archaeosome. The addition of cholesterol
      significantly improved the encapsulation of methylene blue in the archaeosome so
      that the encapsulation efficiency was 61.66 +/- 2.88%. The result of in vitro
      skin permeation showed that methylene blue could pass through skin model
      according to Peppas model and there was about 41.66% release after 6 h, whereas
      no release was observed through dialysis membrane. According to the results of
      the study, it is concluded that archaeosome may be successfully used as drug
      delivery system. 

PMID- 24453700
TI  - Evaluating walking in patients with multiple sclerosis: which assessment tools
      are useful in clinical practice?
AB  - Walking limitations are among the most visible manifestations of multiple
      sclerosis (MS). Regular walking assessments should be a component of patient
      management and require instruments that are appropriate from the clinician's and
      the patient's perspectives. This article reviews frequently used instruments to
      assess walking in patients with MS, with emphasis on their validity, reliability,
      and practicality in the clinical setting. Relevant articles were identified based
      on PubMed searches using the following terms: "multiple sclerosis AND (walking OR
      gait OR mobility OR physical activity) AND (disability evaluation)"; references
      of relevant articles were also searched. Although many clinician- and patient
      driven instruments are available, not all have been validated in MS, and some are
      not sensitive enough to detect small but clinically important changes. Choosing
      among these depends on what needs to be measured, psychometric properties, the
      clinical relevance of results, and practicality with respect to space, time, and
      patient burden. Of the instruments available, the clinician-observed Timed 25
      Foot Walk and patient self-report 12-Item Multiple Sclerosis Walking Scale have
      properties that make them suitable for routine evaluation of walking performance.
      The Dynamic Gait Index and the Timed Up and Go test involve other aspects of
      mobility, including balance. Tests of endurance, such as the 2- or 6-Minute Walk,
      may provide information on motor fatigue not captured by other tests.
      Quantitative measurement of gait kinetics and kinematics, and recordings of
      mobility in the patient's environment via accelerometry or Global Positioning
      System odometry, are currently not routinely used in the clinical setting. 

PMID- 24453701
TI  - Most common types of physical activity self-selected by people with multiple
      sclerosis.
AB  - The promotion of physical activity for people with multiple sclerosis (MS) would
      benefit from information about the common types of physical activity self
      selected by this population. This study examined the most frequent types of
      physical activity self-reported by a large sample of people with MS. The data
      were collected as part of the baseline assessment of a longitudinal investigation
      of physical activity in relapsing-remitting MS (RRMS). The participants (N = 272)
      were sent a battery of questionnaires through the US Postal Service that included
      the Modifiable Activity Questionnaire for assessing types of physical activity
      performed during the previous year. Walking was ranked number 1 for both the
      first and second most common types of physical activity self-selected by people
      with MS, and it was ranked number 4 as the third most common type of self
      selected physical activity. Collectively, 79% of the sample reported walking as a
      frequent form of self-selected physical activity in the previous year. Other
      notable types of physical activities self-selected by people with MS were
      gardening (44%), weight training (34%), bicycling (30%), and calisthenics (20%).
      This information may assist clinicians and practitioners in the development of
      physical activity programs and recommendations for people with MS. 

PMID- 24453702
TI  - Potential benefits of nintendo wii fit among people with multiple sclerosis: a
      longitudinal pilot study.
AB  - We examined the potential of Nintendo Wii Fit (Nintendo Co, Ltd, Kyoto, Japan) to
      increase physical activity (PA) behavior and health among people with multiple
      sclerosis (MS). The study consisted of a repeated-measures design with a baseline
      control period and involved 30 people with MS who had the ability to walk 25 feet
      with or without a cane (26 individuals were included in the analyses). Nintendo
      Wii was set up in the homes of participants, who were prescribed a Wii Fit
      exercise program lasting 14 weeks, 3 days a week. The Physical Activity and
      Disability Survey, Modified Fatigue Impact Scale, and 36-item Short Form Health
      Status Survey were administered three times before participants gained access to
      Wii Fit (control period, at 2-week intervals), and three times after they
      received Wii Fit (posttest 1: immediately after; posttest 2: 7 weeks after;
      posttest 3: 14 weeks after). Mobility, balance, strength, and weight were
      assessed at the first pretest, immediately prior to obtaining access to Wii Fit,
      and 7 weeks after obtaining access to Wii Fit. Results from the questionnaires
      indicated that PA significantly improved at week 7, but at week 14, PA levels
      declined relative to week 7 and the difference was no longer significant compared
      with the control period. Physical assessments indicated that balance and strength
      significantly improved at week 7. One adverse event was reported (repetitive knee
      injury). Physical assessments indicated that people with MS may be able to
      improve their fitness levels by using Wii Fit. Future studies should incorporate
      behavior change strategies to promote long-term use of Wii Fit, and explore
      whether individuals with more severe symptoms of MS can safely use Wii Fit. 

PMID- 24453703
TI  - Effects of a 10-week inspiratory muscle training program on lower-extremity
      mobility in people with multiple sclerosis: a randomized controlled trial.
AB  - Pulmonary muscle weakness is common in ambulatory people with multiple sclerosis
      (MS) and may lead to deficits in mobility function. The purpose of this study was
      to examine the effect of a 10-week home-based exercise program using an
      inspiratory muscle threshold trainer (IMT) on the results of four lower-extremity
      physical performance tests in people with MS. The study design was a two-group
      (experimental-control), pretest-posttest study. Outcome measures consisted of
      pulmonary function measures including maximal inspiratory pressure (MIP), maximal
      expiratory pressure (MEP), and maximal voluntary ventilation (MVV), and the
      following lower-extremity physical performance measures: the 6-Minute Walk (6MW)
      distance, gait velocity (GV), the Sit-to-Stand Test (SST), the Functional Stair
      Test (FST), and a balance test (BAL). A total of 46 ambulatory participants
      (Expanded Disability Status Scale [EDSS] score, 2.0-6.5) with MS were randomly
      assigned to an intervention group (mean EDSS score, 4.1) that received 10 weeks
      of home-based inspiratory muscle training or a nontreatment control group (mean
      EDSS score, 3.2). Of the original 46 participants, 20 intervention group
      participants and 19 control group participants completed the study. Compared with
      the control group, the intervention group made significantly greater gains in
      inspiratory muscle strength (P = .003) and timed balance scores (P = .008). A
      nonsignificant improvement in 6MW distance (P = .086) was also noted in the IMT
      trained group as compared with the control group. This is the first study
      directly linking improvement in respiratory function to improvement in physical
      performance function in people with mild-to-moderate disability due to MS. 

PMID- 24453704
TI  - Asymmetrical hip bone density in multiple sclerosis.
AB  - As multiple sclerosis (MS) may affect one leg more than the other, we predicted
      that bone mineral density (BMD) would be lower in the limb self-identified as
      more affected. Therefore, the purpose of this study was to determine whether
      ambulatory individuals with MS displaying moderate-to-severe lower-extremity
      paresis exhibit asymmetrical femoral neck BMD. Dual-energy x-ray absorptiometry
      was used to assess proximal femoral neck BMD. Lower BMD was observed in the
      proximal femoral neck of the more paretic limb (P = .001) in a group (N = 23) of
      ambulatory individuals with relapsing-remitting MS (RRMS). Our preliminary
      findings suggest that bilateral hip screening may be important in the early
      detection of compromised bone health in ambulatory individuals with RRMS. Further
      research is warranted to fully characterize the factors and mechanisms associated
      with bone loss and identify effective strategies for optimizing bone health in
      people with MS. 

PMID- 24453705
TI  - Editorial.

PMID- 24453706
TI  - Cognition and physical disability in predicting health-related quality of life in
      multiple sclerosis.
AB  - Many studies have shown that multiple sclerosis (MS) has a significant impact on
      patient health-related quality of life (HRQOL), but the relative contributions of
      physical versus cognitive disability are not well established. Most studies have
      relied on HRQOL outcomes that depend largely on patient mood, life satisfaction,
      and personal happiness. The Sickness Impact Profile (SIP) is a measure of HRQOL
      known for its relatively strong emphasis on task completion and activities of
      daily living. As such, the SIP may be less influenced by depression. We sought to
      determine the relative influence of physical disability and cognition, above and
      beyond demographic and disease variables, in predicting HRQOL. Patients (n = 132)
      and healthy controls (n = 26) underwent complete neuropsychological evaluation
      using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery and a
      series of self-report measures assessing depression, fatigue, and HRQOL. The SIP
      was also administered. Correlation analysis and group comparisons revealed
      significant associations between cognition and HRQOL outcomes. Logistic
      regression models comparing the Expanded Disability Status Scale (EDSS) and
      cognitive tests in predicting poor physical HRQOL retained both EDSS and Symbol
      Digit Modalities Test (SDMT) performance, while models predicting poor
      psychosocial and poor overall HRQOL retained only the SDMT. These findings
      support cognition as a significant predictor of overall HRQOL, psychosocial
      HRQOL, and, interestingly, physical HRQOL. 

PMID- 24453707
TI  - Meeting the needs of people with primary progressive multiple sclerosis, their
      families, and the health-care community.
AB  - Although major advances have been made in delaying or preventing progression for
      the relapsing forms of multiple sclerosis (MS), little progress has been made to
      date in disease management for primary progressive MS (PPMS). Treatment
      strategies are largely focused on managing the symptoms of the disease and
      providing counseling and other forms of psychosocial support. The nurse plays a
      major role in managing these patients. This article summarizes a collaborative
      effort by the National Multiple Sclerosis Society and the Multiple Sclerosis
      Association of America to analyze the needs of this patient population and
      respond with programs that will meet those needs. This approach to developing a
      needs assessment is broadly applicable to other patient populations. 

PMID- 24453708
TI  - Caregiver burden among informal caregivers assisting people with multiple
      sclerosis.
AB  - Multiple sclerosis (MS) burdens not only patients but also their informal or
      family caregivers. This study was conducted to identify characteristics of
      caregivers, caregiving, and MS patients receiving informal care that are
      associated with caregiving burden. Data were collected through a national survey
      of informal MS caregivers and analyzed using an ordered logistic regression model
      to identify factors associated with burden. Burden was found to be significantly
      greater among male caregivers than among female caregivers. Moreover, greater
      burden was associated with more frequent patient bladder dysfunction, more hours
      per week spent providing assistance, and greater restriction on the caregiver's
      ability to perform daily activities because of caregiving responsibilities. A
      strong association was found between the mental health status of the caregiver
      and burden. Health professionals should be sensitive to the impact of caregiving
      on the mental health of MS caregivers. The results of this study suggest that
      treating patient bladder dysfunction and facilitating respite care may reduce
      burden and improve the mental health of informal caregivers of people with MS.
      Future research should identify programs and services designed specifically to
      reduce burden experienced by male caregivers. 

PMID- 24453709
TI  - Effect of eszopiclone on sleep disturbances and daytime fatigue in multiple
      sclerosis patients.
AB  - The prevalence of moderate-to-severe sleep problems is significantly higher among
      people with multiple sclerosis (MS) than in the general population. In 2002, we
      found a significant relationship between fatigue and disrupted sleep in patients
      with relapsing-remitting MS (RRMS). The objectives of this study were to
      determine whether eszopiclone (Lunesta; Sunovion Pharmaceuticals Inc,
      Marlborough, MA) was superior to placebo in improving sleep among patients with
      MS-related fatigue and sleep complaints (primary end point); and to assess the
      impact of improved sleep on daytime fatigue and functioning (secondary end
      point). This was a double-blind, placebo-controlled pilot trial lasting 7 weeks.
      Thirty ambulatory adults under age 65 years with RRMS, fatigue, and sleep
      disturbances were randomized to receive either eszopiclone or placebo. The
      outcome measures included subjective and objective changes in sleep-onset latency
      (SOL), total sleep time (TST), wakefulness after sleep onset (WASO), sleep
      efficiency (SE), fatigue scales, and neuropsychological measures of daytime
      functioning. Compared with placebo, eszopiclone was superior only in increasing
      TST. Fatigue improved in both groups, but there was no statistically significant
      correlation between increased TST and improved fatigue, and no statistically
      significant differences were observed between the two groups. Thus, in this
      study, eszopiclone did not improve sleep sufficiently to improve fatigue in MS
      patients. This result may be due to the multifactorial nature of sleep
      disturbances and fatigue in people with MS. 

PMID- 24453710
TI  - The role of postpartum intravenous corticosteroids in the prevention of relapses
      in multiple sclerosis.
AB  - Multiple sclerosis (MS) is most prevalent in women of childbearing age. It is
      well established that the relapse rate decreases during pregnancy but increases
      significantly during the first postpartum trimester. The objective of this
      retrospective study was to evaluate the effectiveness of the administration of 1
      g of intravenous methylprednisolone (IVMP) after delivery in the prevention of MS
      relapses. The study involved 47 women with one or more documented pregnancies;
      each pregnancy was treated as a separate case. There were 50 cases with relapsing
      remitting MS and 2 with secondary progressive MS. The cases were divided into two
      groups: the IVMP group (those who received 1 g of IVMP after delivery) and the no
      IVMP group (those who did not receive IVMP after delivery). There were 39 cases
      in the IVMP group and 13 in the no-IVMP group. During the first postpartum
      trimester, relapses occurred in 17.9% of the IVMP group, compared with 46.2% of
      the no-IVMP group (P = .0448). The difference in relapse percentage between the
      two groups during the second and third postpartum trimesters was not
      statistically significant. Our study shows a statistically significant benefit of
      postpartum IVMP administration in reducing MS relapses. 

PMID- 24453711
TI  - Successful management of a neurology infusion practice.
AB  - The increasing use of infusible biologic therapies, including the novel
      monoclonal antibody natalizumab for the treatment of relapsing forms of multiple
      sclerosis, has elicited much interest among neurologists in the provision of in
      office infusions for their patients. An in-office infusion center may offer
      neurologists a means to provide integrated care for their patients in a familiar
      and supportive environment. This setting is especially convenient for chronically
      ill patients, allowing them to receive high-quality care under the direct
      supervision of their neurologist and facility staff. By administering infusible
      treatments in a neurology practice rather than referring patients to a hospital
      or oncology/hematology-based infusion center, the primary neurologist can more
      closely monitor clinical outcomes, treatment adherence, and the occurrence of
      adverse effects. In addition, there is greater opportunity for patient
      interaction and education, which can strengthen relationships with clinical
      caregivers. This model is also applicable to multispecialty or hospital-based
      neurology groups desiring to integrate neurology infusion services. In this
      article, we discuss overall management strategies; staffing and scheduling
      issues; general coding, billing, and reimbursement methodologies; and additional
      financial considerations. 

PMID- 24453712
TI  - Editorial.

PMID- 24453713
TI  - The evolving role of the multiple sclerosis nurse: an international perspective.
AB  - A greater understanding of the pathogenesis of multiple sclerosis (MS) and the
      need for treatments with increased efficacy, safety, and tolerability have led to
      the ongoing development of new treatments. The evolution of treatments for MS is
      expected to have a dramatic impact on the entire health-care team, especially MS
      nurses, who build strong collaborative partnerships with their patients. MS
      nurses help patients better understand their disease and treatment options,
      facilitate the initiation and management of treatment, and encourage adherence.
      With new oral therapies entering the market, the potential for increased
      efficacy, tolerability, adherence, and convenience for patients is evident.
      However, the resulting change in the treatment paradigm means that the skill set
      required of an MS nurse will inevitably expand. There will be a growing need for
      professional training and development to ensure that nurses are familiar with the
      wider range of treatments and their specific modes of action, dosing schedules,
      and benefit/risk profiles. In addition, the MS nurse's role will expand to
      include management of the complex monitoring needs specific to each therapy. This
      article explores how the role of the MS nurse is evolving with the development of
      new MS therapies, including novel oral therapies. 

PMID- 24453714
TI  - Validation of the NARCOMS Registry: Tremor and Coordination Scale.
AB  - Tremor secondary to multiple sclerosis (MS) can be severely disabling but remains
      understudied. The development of brief, acceptable patient-reported measures of
      tremor could facilitate further study. We aimed to assess the criterion and
      construct validity of the Tremor and Coordination Scale (TACS) used by the North
      American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Forty-four
      patients with MS completed the TACS and Performance Scales and underwent a
      neurologic examination (Expanded Disability Status Scale; EDSS) and evaluation
      with the Multiple Sclerosis Functional Composite (MSFC). We assessed criterion
      and construct validity with Spearman rank correlations between the TACS and the
      following measures: EDSS, Nine-Hole Peg Test (NHPT) of the MSFC, age, body-mass
      index (BMI), the hand function and mobility domains of the Performance Scales,
      and the Physical and Mental Composite Scores of the 36-item Short Form Health
      Status Survey (SF-36). The median (interquartile range; IQR) score on the TACS
      was 1 (0.5-2.0). The TACS correlated moderately with the cerebellar Functional
      System Score (FSS) (r = 0.51; 95% confidence interval [CI], 0.24-0.70) and with
      the NHPT (r = -0.51; 95% CI, -0.70 to -0.29). The TACS correlated with the hand
      (r = 0.60; 95% CI, 0.36-0.76) and mobility (r = 0.56; 95% CI, 0.31-0.73) domains
      of the Performance Scales. The TACS did not correlate significantly with age (r =
      -0.11; 95% CI, -0.40 to 0.19) or BMI (r = 0.15; 95% CI, -0.15 to 0.43). These
      findings support the criterion and construct validity of the TACS. Further
      evaluation is needed to establish the test-retest reliability of the scale and
      its responsiveness to change. 

PMID- 24453715
TI  - Impact of a 10-week individualized exercise program on physical function and
      fatigue of people with multiple sclerosis: a pilot study.
AB  - Research has found that people with multiple sclerosis (MS) who engage in
      exercise programs experience improvements in physical and psychological health,
      resulting in enhanced quality of life. These studies have involved structured
      exercise protocols, but few have examined the effects of an individualized
      exercise program allowing for peer socialization. The purpose of this study was
      to investigate the effects of a 10-week individualized exercise program offering
      opportunities to socialize with peers on fatigue and physical functioning in
      people with MS. Thirteen individuals with a physician diagnosis of MS were
      enrolled in a 10-week exercise program at Nazareth College in Rochester, New
      York. Eleven participants (9 female, 2 male; mean +/- SD age, 55.0 +/- 7.06
      years) completed the study. The following qualitative and quantitative measures
      were used for evaluation before and after the exercise program: Multiple
      Sclerosis Quality of Life-54 (MSQOL-54), Activities-specific Balance Confidence
      (ABC) scale, Modified Fatigue Impact Scale (MFIS), Timed Up and Go (TUG) test,
      Timed 10-Meter Walk (T10MW) test, functional reach test, and single-leg stance
      (SLS) test. Statistically significant differences were found for the TUG (P =
      .005), T10MW (P = .014), and MFIS physical functioning subscore (P = .039). The
      results showed significant increases in gait speed and mobility as well as
      decreased impact of fatigue on physical functioning after the 10-week exercise
      program. 

PMID- 24453716
TI  - A comprehensive cost-effectiveness analysis of treatments for multiple sclerosis.
AB  - The purpose of this study was to examine the cost-effectiveness of four disease
      modifying drugs (DMDs) used to treat multiple sclerosis (MS): glatiramer acetate
      (GA; Copaxone), interferon beta-1a (IFNbeta-1a) intramuscular (IM) injection
      (Avonex), IFNbeta-1a subcutaneous (SC) injection (Rebif), and interferon beta-1b
      (IFNbeta-1b) SC injection (Betaseron). Cost-effectiveness analyses are useful in
      countering the financial uncertainties and treatment efficacy concerns faced by
      people with MS. We conducted simulation analyses of the principal findings of a
      2009 study by Goldberg et al. (Goldberg LD, Edwards NC, Fincher C, et al:
      Comparing the cost-effectiveness of disease-modifying drugs for the first-line
      treatment of relapsing remitting multiple sclerosis. J Manag Care Pharm.
      2009;15:543-555) to frame the researchers' findings from the perspectives of cost
      conscious and cost-neutral MS patients. We found that for the cost-conscious
      consumer, the ranking of most (1) to least (4) preferred DMDs was 1) IFNbeta -1a
      IM (Avonex), 2) GA (Copaxone), 3) IFNbeta-1a SC (Rebif), and 4) IFNbeta-1b SC
      (Beta-seron). For the cost-neutral consumer who places priority on effectiveness
      over costs, the ranking was 1) IFNbeta-1a SC (Rebif), 2) IFNbeta-1b SC
      (Betaseron), 3) GA (Copaxone), and 4) IFNbeta-1a IM (Avonex). Future studies
      could examine cost-effectiveness over extended periods of time (eg, 15-20 years)
      and more closely examine the cost-effectiveness of natalizumab (Tysabri) relative
      to the four primary DMDs. 

PMID- 24453717
TI  - Monitoring my multiple sclerosis: a patient-administered health-assessment scale.
AB  - Optimal health of people with multiple sclerosis (MS) can be promoted by
      patients' sharing of health information gained through periodic self-monitoring
      with their health-care providers. The purpose of this study was to develop a
      valid and reliable self-administered scale to obtain information about MS
      patients' health status and the impact of the disease on their daily lives. We
      named this scale "Monitoring My Multiple Sclerosis" (MMMS). A cross-sectional
      survey was conducted of 171 MS patients who completed the MMMS and Patient
      Determined Disease Steps (PDDS) scales and provided information on their MS
      disease classification and demographic characteristics. Data analysis included
      several parametric procedures. Factor analysis of the 26-item MMMS resulted in
      four factors with satisfactory alpha reliability coefficients for the total scale
      (0.90) and factored subscales: Physical (0.85), Relationships (0.80), Energy
      (0.70), and Cognitive/Mental (0.67). Analysis of variance demonstrated that the
      total scale and the Physical subscale, but not the Relationships subscale, showed
      significantly worse functioning for patients with either moderate or severe
      disability as measured by the PDDS than for patients with mild disability (P <
      .001). The Cognitive/Mental subscale showed significantly worse functioning for
      patients with moderate disability than for patients with mild disability (P <
      .05). However, the Energy subscale showed significantly worse functioning among
      moderately disabled patients than among severely disabled patients (P < .01).
      Independent t tests demonstrated that patients classified as having secondary
      progressive multiple sclerosis had significantly worse scores on the total MMMS
      (P < .05) and the Physical subscale (P < .001) than those classified as having
      relapsing-remitting multiple sclerosis. The MMMS demonstrated satisfactory
      reliability and validity and is recommended for use by MS patients and their
      health-care providers as a mechanism to promote the sharing of health
      information, to the benefit of both patients and providers. 

PMID- 24453719
TI  - Editorial.

PMID- 24453718
TI  - Perspectives on self-management in multiple sclerosis: a focus group study.
AB  - The aim of this study was to elucidate the experience of self-management among
      people with multiple sclerosis (MS) and gather their input to inform a self
      management intervention. Twelve people with MS participated in focus groups in
      which they were asked open-ended questions about MS symptoms, challenges,
      overcoming challenges, symptom management, and treatment preferences. The results
      suggest four major themes: 1) "The Everyday Experience of MS," including comments
      about symptoms and their impact on functioning; 2) "Motivation for Self
      Management," including descriptions of motivation originating from physical
      necessity, success with other management techniques, and external sources; 3)
      "Coping Strategies and Skills," including descriptions of changing behaviors,
      expanding social support networks, finding resources, utilizing medical
      treatment, and monitoring symptoms; and 4) "Vision for a Self-Management
      Intervention," including suggestions that an intervention be individualized, be
      motivating, and provide resources. The results of this study can inform the
      design and implementation of self-management interventions. Experiences described
      by participants are consistent with other qualitative reports suggesting the
      active role people with MS play in managing their condition. Intervention
      approaches must consider the complex constellation of symptoms associated with MS
      and provide individualized treatments that enhance the person's ability to manage
      their symptoms, barriers presented by such symptoms, and their health care. 

PMID- 24453720
TI  - Developing a wellness program for people with multiple sclerosis: description and
      initial results.
AB  - Because multiple sclerosis (MS) is a multidimensional chronic disease, effective
      management of the illness requires a multidimensional approach. We describe a
      wellness program that was designed to facilitate positive health choices
      throughout the course of MS and present initial data analyses. We hypothesized
      that over the course of the program, participants would demonstrate improvement
      in the domains assessed. The wellness program included educational sessions in
      physical, mental, social, intellectual, and spiritual domains specifically
      targeting improved self-efficacy, physical functioning, coping skills, symptom
      management, and nutrition. An outcomes data collection software program was
      adapted to facilitate real-time patient self-report and clinician entry data
      collection for many domains throughout the wellness program. Initial assessment
      of serial measures (intake to discharge) from 65 people with MS showed
      improvement in several domains, including functional status (P < .05), fatigue (P
      < .05), fear-avoidance beliefs regarding physical activities (P < .05),
      depression (P < .05), somatization (P < .05), and pain (P < .05). In addition,
      using a model of risk for interpersonal distress, patients whose risk of elevated
      depression and anxiety decreased over the course of the program reported greater
      gains in functional status (P < .05). The results suggest possible future
      treatment strategies and indicate strengths and weaknesses of the wellness
      program, which are being used to improve the program. 

PMID- 24453721
TI  - Effects of meditation on pain and quality of life in multiple sclerosis and
      peripheral neuropathy: a pilot study.
AB  - The objective of this study was to determine whether meditation affects pain and
      quality of life in people with multiple sclerosis (MS) and peripheral neuropathy
      (PN). A total of 22 patients (10 with MS, 12 with PN) participated in a weekly
      meditation class over a 2-month period. A total of 18 controls (7 with MS, 11
      with PN) received standard care. Primary outcome assessments were based on the 36
      item Short Form Health Status Survey (SF-36) and a visual analogue scale (VAS)
      for pain at baseline and at 2 months. Secondary outcome measures included the
      Neuropathy Impairment Score (NIS) for PN patients and the Patient-Determined
      Disease Steps (PDDS) questionnaire and 5-item Modified Fatigue Impact Scale (MFIS
      5) for MS patients. After 2 months, study participants who practiced meditation
      reported an improvement in pain on the VAS (P = .035 combined group), summed
      physical health scores on the SF-36 (P = .011 MS, P = .014 PN), summed mental
      health scores (P = .02 combined group), vitality (P = .005 combined group), and
      physical role (P = .003 combined group). A significant improvement was also
      observed for bodily pain (P = .031) in MS patients. In contrast, no significant
      differences before and after the intervention were observed for controls.
      Regarding the secondary measure of fatigue, improved scores for the cognitive and
      psychosocial components of the MFIS were noted in MS patients in the intervention
      group (P = .037, P = .032). No statistically significant changes were observed in
      the NIS for PN patients or in PDDS scores for MS patients. Meditation may be
      helpful in reducing pain and improving quality of life in patients with MS and
      PN. The lack of changes seen in mobility (MS) and sensorimotor deficits (PN)
      suggests that meditation may not affect the overall clinical course. 

PMID- 24453722
TI  - The impact of gait disability on the calibration of accelerometer output in
      adults with multiple sclerosis.
AB  - Accelerometer activity counts have been correlated with energy expenditure during
      treadmill walking among ambulatory adults with multiple sclerosis (MS). This
      study examined the effects of gait disability on 1) the association between rates
      of energy expenditure and accelerometer output in overground walking and 2) the
      calibration of accelerometer output for quantifying time spent in moderate-to
      vigorous physical activity (MVPA) in people with MS. The sample consisted of 24
      individuals with MS, of whom 10 reported gait disability based on Patient
      Determined Disease Steps (PDDS) scores. The participants undertook three 6-minute
      periods of overground walking while wearing an accelerometer and a portable
      metabolic unit (K4b2, Cosmed, Rome, Italy). In the first period of walking, the
      participants walked at a self-selected, comfortable speed. In the two subsequent
      walking periods, participants walked at speeds above and below (+/-0.5 mph) the
      comfortable walking speed, respectively. Strong linear relationships were
      observed between rates of accelerometer activity counts and energy expenditure
      during walking in the overall sample (R(2) = 0.90) and subsamples with (R(2) =
      0.88) and without gait disability (R(2) = 0.91). The slope of the relationship
      was significantly steeper in the subsample with gait disability (beta= 0.0049)
      than in the subsample without gait disability (beta= 0.0026). The difference in
      slopes resulted in a significantly lower cut-point for MVPA (1886 vs. 2717
      counts/min) in those with gait disability. These findings provide a metabolic cut
      point for quantifying time spent in MVPA in people with MS, both with and without
      gait disability. 

PMID- 24453723
TI  - Informal caregivers assisting people with multiple sclerosis: factors associated
      with the strength of the caregiver/care recipient relationship.
AB  - The objective of this study was to identify characteristics of informal
      caregivers, caregiving, and people with multiple sclerosis (MS) receiving this
      assistance that are associated with the strength of the care-giver/care recipient
      relationship. Data were collected in a national survey of informal caregivers and
      analyzed using an ordered logistic regression model to identify factors
      associated with caregiver perceptions of the strength of the relationship with
      the person with MS. The overall health of the person with MS was significantly
      associated with caregiver perceptions that providing assistance strengthened the
      caregiver/care recipient relationship, with poor health having a negative impact
      on the relationship. A spousal relationship between the caregiver and the person
      with MS was associated with significantly lower perceptions of a strengthened
      relationship. Conversely, caregiver perceptions that MS symptoms interfered with
      the independence of the person with MS in daily life were associated with
      caregiver perceptions of a strengthened relationship. Longer duration of
      caregiving and more hours per week spent providing assistance also were
      associated with a stronger relationship. In contrast, we found a significant
      negative association between caregiver perceptions that assisting the person with
      MS was burdensome and the strength of the relationship. Similarly, higher levels
      of education among caregivers tended to have a significantly negative impact on
      the caregiver/care recipient relationship. Our findings highlight the importance
      of addressing the needs and concerns of spousal caregivers. Health professionals
      who treat informal caregivers, as well as those treating people with MS, should
      be sensitive to the impact caregiving has on caregivers, especially spouses
      providing assistance. 

PMID- 24453724
TI  - Editorial.

PMID- 24453725
TI  - Fully Searchable Online Edition of IJMSC to Launch in April.

PMID- 24453726
TI  - Perceived met and unmet health-care needs in a community population with multiple
      sclerosis.
AB  - Community-based studies are required to accurately describe the supportive
      services needed by people with multiple sclerosis (MS). Characteristics that
      influence (or result from) care-seeking may introduce bias into other types of
      studies. The Participation and Activity Limitation Survey (PALS) was a post
      census survey conducted by Statistics Canada in association with a 2006 national
      census. The PALS collected data from a sample of 22,513 respondents having health
      related impairments according to their census forms. The survey collected self
      reported diagnostic data and obtained ratings for items assessing impairment as
      well as perceived met and unmet needs for care and support. It identified 245
      individuals with MS, leading to an estimated (weighted) population prevalence of
      0.2% (200 per 100,000). As expected, those with MS reported more-severe health
      problems than did those with other types of disability, particularly in the areas
      of mobility, dexterity, and cognition; they were also more likely to report
      having multiple caregivers. People with MS also reported more unmet health-care
      needs than did those with other forms of disability, particularly with respect to
      meal preparation, housework, shopping, and chores. Despite their more negative
      health status and greater reliance on caregivers, people with MS reported
      participation in society comparable to that of people without MS. Thus, people
      with MS report greater needs than do people with other forms of health-related
      disability and utilize supportive services more often. However, they also report
      higher levels of unmet needs. The substantial needs of people with MS are only
      partially addressed by existing services. 

PMID- 24453727
TI  - Depression levels and interferon treatment in people with multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common cause of neurologic disease in young
      and middle-aged adults, and 75% of patients are female. Nearly one in two
      patients with MS will experience clinically significant depression-approximately
      three times the prevalence rate in the general population. This study used a
      cross-sectional approach to examine the link between depression levels and use of
      interferon medications among individuals with MS. Data were collected from 694
      patients of the Multiple Sclerosis Comprehensive Care Center at Holy Name Medical
      Center in Teaneck, New Jersey. Analysis of variance was used to compare
      depression scores between patients taking and not taking interferons. Regression
      analyses with depression scores as the dependent variable were also conducted.
      The Beck Depression Inventory (BDI) was reduced to a set of dimensions by
      principal components analysis. Two components were identified, reflecting somatic
      and cognitive symptoms. The results showed no significant relationship between
      depression levels and interferon treatment. Significant associations were
      observed between depression and both age and disability status, with younger,
      more disabled patients tending to be more depressed. 

PMID- 24453728
TI  - Adherence to first-line disease-modifying therapy for multiple sclerosis in
      kuwait.
AB  - The aim of this retrospective study was to determine the rate of nonadherence to
      disease-modifying therapies (DMTs) among multiple sclerosis (MS) patients in
      Kuwait and to identify reasons for patient discontinuation of long-term therapy.
      Using a newly established MS registry at our institution, we collected data on MS
      patients' demographics, clinical characteristics, disability measures, and
      continuation or discontinuation of first-line DMTs. Reasons for nonadherence were
      divided into four categories: adverse events, inconvenience, perceived lack of
      efficacy, and physician-documented disease progression. Of 212 eligible patients,
      40.1% were found to be nonadherent to first-line DMTs. In the nonadherent group,
      the female-to-male ratio was 1.75:1 and the mean age at disease onset was 26.8
      years. Of this group, 69.4% of patients had a relapsing-remitting course, 18.8%
      had a secondary progressive course, and 11.8% had clinically isolated syndrome.
      Compared with the adherent group, the nonadherent group had a shorter mean
      disease duration (P = .014) and a greater likelihood of having Expanded
      Disability Status Scale (EDSS) scores of 3 or lower (67.1% vs. 48.0%; P = .007).
      Inconvenience was the most common reason for nonadherence (32.9%), followed by
      perceived lack of efficacy (25.9%), adverse events (23.5%), and physician
      documented disease progression (17.7%). In summary, the rate of nonadherence to
      first-line DMTs in MS patients at our institution is considered high. Most
      nonadherent patients had a short disease duration and low EDSS scores.
      Inconvenience and perceived lack of efficacy were the most common reasons for
      nonadherence. The results demonstrate a need to improve treatment adherence among
      MS patients in Kuwait through providing better patient education, improving
      communication between patients and health-care providers, defining therapy
      expectations, and instituting new therapeutic techniques. 

PMID- 24453729
TI  - Step-length variability in minimally disabled women with multiple sclerosis or
      clinically isolated syndrome.
AB  - Gait is one of the most frequently impaired bodily functions in multiple
      sclerosis (MS). Determining abnormal parameters of gait in early MS could
      influence MS treatment and rehabilitation. The purpose of this study was to
      determine whether increased step-length variability could be detected in
      minimally disabled patients with MS or clinically isolated syndrome (CIS) using a
      sensored walkway gait analysis system. Nine participants with MS/CIS and nine age
      and gender-matched controls were recruited for this study. MS/CIS participants
      underwent a neurologic examination, and all participants completed a screening
      interview. Each participant completed three walks at a self-selected pace and
      three walks at a brisk pace across the GAITRite walkway (MAP/CIR Inc, Havertown,
      PA). Mean values for step-length variability, step length, and velocity were
      calculated for each participant's self-selected and brisk trials. Independent t
      tests were used to compare MS/CIS participants with controls, and effect sizes
      were calculated. Step-length variability in the left leg at the self-selected
      pace was found to be greater in participants with MS/CIS than in controls,
      although no significant differences were found in velocity or step length. Step
      length variability measurement shows promise in detecting subtle gait
      dysfunction. Larger, prospective studies exploring step-length variability may
      determine its clinical viability for detecting subtle gait dysfunction and could
      lead to improved prognostication of disability progression in MS. 

PMID- 24453730
TI  - Summary of eye examinations of 284 patients with multiple sclerosis.
AB  - The aim of this article is to report the findings of ocular examinations in a
      group of patients diagnosed with multiple sclerosis who were referred to the eye
      department of the Nationaal Multiple Sclerosis Centrum of Melsbroek, Belgium,
      from 2007 to 2010. Patients were evaluated by a single examiner, who noted visual
      acuity for distance, the state of the optic disks, oculomotor balance, and the
      presence of nystagmus, uveitis, trigeminal neuralgia, and facial palsy. The
      sample consisted of 284 adults born between 1920 and 1989: 111 males and 173
      females. There were 51 patients with a corrected visual acuity in the better
      seeing eye of less than 6/20. The optic nerve head was found to be normal in 245
      eyes. Nystagmus was noted in 104 patients. Diplopia at distance was found to be
      present in 20 males, of whom 12 also had nystagmus, and in 31 females, of whom 13
      also had nystagmus. Oscillopsia was present in 6 males and 11 females. In
      summary, most of the patients evaluated had sufficient visual function to allow
      performance of activities of daily living without help. A small number of
      patients had visual failure due to dysfunction of the visual sensory pathway
      and/or disturbances of oculomotor balance, often of a supranuclear origin,
      resulting in considerable disability. 

PMID- 24453731
TI  - Relapsing-remitting multiple sclerosis patients' experience with natalizumab: a
      phenomenological investigation.
AB  - This phenomenological investigation was undertaken to gain a better understanding
      of multiple sclerosis (MS) patients' experience with natalizumab (Tysabri; Biogen
      Idec Inc, Cambridge, MA) treatment and its impact on their quality of life (QOL).
      Twenty MS patients who were receiving natalizumab treatment were recruited by the
      physicians, nurse practitioners, nurses, and social worker of the William C.
      Baird Multiple Sclerosis Center in Buffalo, New York, between March 2009 and
      November 2009. Patients were invited to participate if they had relapsing
      remitting MS, had received at least six treatments of natalizumab, and could
      articulate their experience. An interviewer obtained informed consent, gathered
      basic demographic information, and then tape-recorded the participants' accounts
      of their experience with natalizumab. The audio-recorded interviews were
      transcribed and de-identified before being submitted to the investigators for
      analysis. The Atlas.ti qualitative data analysis program (Scolari, Berlin,
      Germany) was used to manage the data. Patients found natalizumab easy to tolerate
      and effective; moreover, they described improvement in their QOL. Patients must
      weigh the benefits of control of their MS against the increased risk of
      developing progressive multifocal leukoencephalopathy with natalizumab treatment.
      Information from this study will be used to educate professionals involved in MS
      patient care as well as patients and families considering treatment with
      natalizumab. 

PMID- 24453733
TI  - Editorial.

PMID- 24453732
TI  - Injectable multiple sclerosis medications: a patient survey of factors associated
      with injection-site reactions.
AB  - Although injection-site reactions (ISRs) occur with US Food and Drug
      Administration-approved injectable disease-modifying therapies (DMTs) for
      multiple sclerosis, there are currently few reports of real-world data on ISR
      management strategies or possible correlations between ISRs and patient
      demographics, disease characteristics, and missed injections. Patient-reported
      data on the use of DMTs, patient demographic and disease characteristics, missed
      injections, and ISR reduction strategies were collected via e-mail, a patient
      registry (www.ms-cam.org), and a Web-based survey. Of the 1380 respondents, 1201
      (87%) indicated that they had used injectable DMTs, of whom 377 (31%) had used
      intramuscular (IM) interferon beta-1a (IFNbeta-1a), 172 (14%) had used
      subcutaneous (SC) IFNbeta-1a, 183 (15%) had used SC IFNbeta-1b, and 469 (39%) had
      used glatiramer acetate (GA). The majority of respondents were older (73% were
      >=40 years), female (79%), married or living with a partner (72%), white (94%),
      and nonsmoking (82%). Injection-site reaction incidence, grouped according to
      severity, varied among DMTs, with IM IFNbeta-1a causing significantly (P < .001)
      fewer mild, moderate, or severe ISRs than the other therapies. Female sex and
      younger age were significantly (P < .05) associated with more moderate ISRs among
      users of IM IFNbeta-1a, SC IFNbeta-1b, and GA. Nonwhites reported severe ISRs
      more often than whites. For all DMTs injection-site massage and avoidance of
      sensitive sites were the most frequently used strategies to minimize ISRs. These
      data may help identify patients with characteristics associated with a higher
      risk for ISRs, allowing health-care professionals to provide anticipatory
      guidance to patients at risk for decreased adherence or discontinuation. 

PMID- 24453734
TI  - Introduction: cognitive dysfunction in multiple sclerosis.

PMID- 24453735
TI  - The Need for Screening, Assessment, and Treatment for Cognitive Dysfunction in
      Multiple Sclerosis: Results of a Multidisciplinary CMSC Consensus Conference,
      September 24, 2010.
AB  - Cognitive dysfunction is observed in about half of people with multiple sclerosis
      (MS), and MS health-care professionals face the challenge of screening,
      assessing, and treating patients for cognitive problems. Considering the
      inconsistent or limited empirical evidence to assist in this task, a
      multidisciplinary consensus conference of MS experts, sponsored by the Consortium
      of Multiple Sclerosis Centers (CMSC), was held on September 24, 2010, to address
      these issues. Key articles from the literature on these topics were distributed
      prior to the meeting, and CMSC member professionals were surveyed on clinical
      practices related to screening, assessment, and treatment for cognitive problems.
      The purpose of the meeting was threefold: 1) to achieve a multidisciplinary
      perspective on practices for screening, monitoring, evaluating, and treating MS
      patients for cognitive problems; 2) to propose consensus candidate measures for
      screening and/or monitoring for cognitive problems in MS that neurologists or
      nurses might administer on a regular basis; and 3) to propose consensus treatment
      approaches from a multidisciplinary perspective. This article summarizes the
      conclusions of the conference participants and provides preliminary suggestions
      for screening and brief assessment. 

PMID- 24453736
TI  - Prediction of driving ability in people with relapsing-remitting multiple
      sclerosis using the stroke driver screening assessment.
AB  - The ability to drive is often affected in individuals with multiple sclerosis
      (MS) because of the motor, visual, or cognitive deficits commonly associated with
      the condition. In this study, we investigated the accuracy with which the Stroke
      Driver Screening Assessment (SDSA), an established battery for the prediction of
      driving performance of stroke survivors, would predict driving performance of
      individuals with MS. Driving performance of 44 individuals with relapsing
      remitting MS (mean +/- SD age, 46 +/- 11 years; 37 females and 7 males) who were
      currently driving at least once a month was predicted using their performance on
      the SDSA. Outcomes of a road test and the Useful Field of View (UFOV) test were
      used as measures of driving ability. Participants' performance on both the road
      and UFOV tests was predicted with more than 80% accuracy. The SDSA was more
      accurate in predicting who would pass the two tests than who would fail the
      tests. The SDSA battery appears to be a good predictor of driving performance of
      individuals with relapsing-remitting MS, especially those who have sufficient
      cognitive skills to continue driving. Larger studies are needed to definitively
      establish its predictive accuracy and confirm the validity of the predictions. 

PMID- 24453737
TI  - Intra-individual Variability as a Measure of Information Processing Difficulties
      in Multiple Sclerosis.
AB  - Deficits in information processing speed are among the most commonly reported
      impairments in multiple sclerosis (MS) and are generally assessed by evaluating
      mean-level performance on time-limited tests. However, this approach to assessing
      performance ignores potential within-subject differences in MS patients that may
      be useful for characterizing cognitive difficulties in MS. An alternative method
      of measuring performance is by examining the degree of within-subject
      variability, termed intra-individual variability (IIV). Intra-individual
      variability provides information about the characteristics of a person's
      performance over time and may provide novel information about cognitive
      functioning in MS. This study examined IIV in performance on the Computerized
      Test of Information Processing (CTIP) using two within-subject variability
      methods: individual standard deviation and coefficient of variation. Eighteen
      females with relapsing-remitting MS and 18 healthy female controls completed the
      CTIP. Consistent with previous research, MS patients demonstrated slower overall
      mean performance on the CTIP compared with controls, with patients becoming
      increasingly slower than controls as cognitive demands increased across the
      tasks. Furthermore, MS patients demonstrated greater IIV as measured by
      individual standard deviations on all subtests of the CTIP, even with mean-level
      group differences as well as practice and learning effects controlled. These
      between-group differences were not found when the coefficient of variation, a
      more coarse measure of within-subject variability, was used. Intra-individual
      variability was also found to be a better predictor of neurologic status than
      mean-level performance. These results suggest that IIV may provide unique insight
      into cognitive functioning in MS. 

PMID- 24453738
TI  - Information processing and magnetic resonance imaging indices of brain pathology
      in multiple sclerosis.
AB  - Accumulation of central nervous system (CNS) pathology affects cognitive
      processing speed and efficiency and is thought to underlie attentional and
      executive deficits in multiple sclerosis (MS). Most clinical neuropsychological
      tests are multifactorial and are limited in their sensitivity to specific
      cognitive processes. This may, in part, account for the low to moderate
      correlations between clinical test results and magnetic resonance imaging (MRI)
      indices of brain pathology. We compared the ability of a clinical and an
      experimental test of cognitive processing speed to differentiate domain-specific
      cognitive changes in MS, and examined relations between test performance and MRI
      measures of brain pathology. Twelve MS patients and 12 controls completed the
      Paced Auditory Serial Addition Test (PASAT) and the Attention Networks Test
      Interactions (ANT-I), a computerized response latency task. Subjects also had MRI
      scans that included T1, T2, and fluid-attenuated inversion recovery (FLAIR)
      sequences that provided global and localized volumetric measures. Patients made
      more errors on the PASAT and were slower on the ANT-I. The ANT-I also revealed
      specific deficits in response inhibition. In addition, ANT-I performance was
      associated with changes in a number of MRI measures, which was not the case for
      the PASAT. Reaction time paradigms that manipulate within-task demands on
      distinct cognitive functions may provide meaningful markers of brain disease
      burden in MS. 

PMID- 24453739
TI  - Tests of information processing speed: what do people with multiple sclerosis
      think about them?
AB  - Reduction in information processing speed (IPS) is a key deficit in multiple
      sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT), Symbol Digit
      Modalities Test (SDMT), and Computerized Test of Information Processing (CTIP)
      are used to measure IPS. Both the PASAT and SDMT are sensitive to deficits in
      IPS. The CTIP, a newer task, also shows promise. The PASAT has several
      limitations, and it is often perceived negatively by patients. Yet little
      supporting quantitative evidence of such perceptions has been presented.
      Therefore, in this study, subjective ratings of likeability, difficulty, and
      appropriateness of the PASAT, CTIP, and SDMT were obtained. Ratings were compared
      between MS patients and healthy controls. It was hypothesized that ratings of the
      PASAT would differ significantly from those of the SDMT and CTIP. The
      relationship between subjective ratings and objective performance was evaluated.
      Sixty-nine MS patients and 68 matched controls rated the three tests in terms of
      likeability, difficulty, and appropriateness for capturing cognitive deficits
      often associated with MS using a Likert scale. Both groups rated the PASAT as
      most difficult and least likeable. The MS group rated the PASAT and SDMT as more
      appropriate for measuring MS-related deficits than the CTIP. Subjects who
      performed better on the PASAT were more likely to rate it as easier. Ratings of
      the SDMT and CTIP did not vary consistently with performance. The findings lend
      quantitative support to the common belief that the PASAT is perceived as
      unpleasant. Other tests are available that are similarly sensitive to deficits in
      IPS and more palatable to the patient. 

PMID- 24453740
TI  - Improvement of neuropsychological function in cognitively impaired multiple
      sclerosis patients treated with natalizumab: a preliminary study.
AB  - Treatment with natalizumab has been shown to reduce physical disability in people
      with multiple sclerosis (MS). However, its effect on neuropsychological
      dysfunction is not well understood. A single-center, open-label, retrospective
      study was conducted to evaluate the effect of natalizumab treatment on
      neuropsychological function in individuals with relapsing-remitting multiple
      sclerosis (RRMS) who had a measurable neuropsychological deficit prior to
      natalizumab treatment. A total of 40 MS patients (mean age, 48.5 years; 77.5%
      female) were evaluated on a neuropsychological battery of nine tests designed for
      MS patients before and after 6 or more months of treatment with natalizumab.
      Posttreatment neuropsychological testing results were compared to baseline
      results. The mean baseline Neuropsychological Impairment Index was 0.49, which
      improved to 0.41 after treatment (P = .0002) as analyzed using the Wilcoxon
      signed rank test. The mean Beck Depression Inventory-II (BDI-II) score improved
      by 2.45 points (P = .001). The mean Expanded Disability Status Scale (EDSS) score
      improved by 0.30 (P = .02). A total of 52.5% of patients showed
      neuropsychological improvement, while 30.0% showed no change and 17.5% had
      worsening. Magnetic resonance imaging showed no changes. The specific prior
      disease-modifying therapy had no influence on the results for natalizumab effect.
      The results of this study show that natalizumab can stabilize or improve
      neuropsychological function in RRMS patients. The improvement was consistent
      with, but apparently independent of, improvement in depression and physical
      disability. 

PMID- 24453742
TI  - Value of a confidant relationship in psychosocial care of people with multiple
      sclerosis.
AB  - WE EXPLORED THE EFFECTS OF LIVING WITH MULTIPLE SCLEROSIS (MS) ON A PRIMARY
      RELATIONSHIP: that between the person with MS and his or her closest confidant.
      We anticipated that this would enhance understanding of the meaning of
      psychosocial support from the perspective of people with MS. Using a
      phenomenological qualitative approach, we interviewed 33 people with MS and the
      people they identified as providing psychosocial support to them (their
      confidants). The results were presented to a range of health-care workers in two
      focus groups to explore their responses. Two additional focus groups were held
      with the participants with MS to add depth and clarity to the findings. Three
      major themes emerged from the interviews: 1) People with MS do not want to be
      defined by their condition and want to live as normal a life as possible. 2) The
      confidant helps to maintain this sense of normality. 3) Both the person with MS
      and the confidant value the relationship and together try to manage the realities
      of living with MS. The findings indicate the need to raise awareness among MS
      care professionals about the value of the confidant relationship. Training
      professionals to discuss emotional issues with clients and increasing
      collaboration with agencies that provide emotional support will facilitate a more
      holistic approach to care. 

PMID- 24453741
TI  - Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the
      Clinical Classification of Multiple Sclerosis and Assessment of Its Course: A
      Report from an International CMSC Consensus Conference, March 5-7, 2010.
AB  - It has recently been suggested that the Lublin-Reingold clinical classification
      of multiple sclerosis (MS) be modified to include the use of magnetic resonance
      imaging (MRI). An international consensus conference sponsored by the Consortium
      of Multiple Sclerosis Centers (CMSC) was held from March 5 to 7, 2010, to review
      the available evidence on the need for such modification of the Lublin-Reingold
      criteria and whether the addition of MRI or other biomarkers might lead to a
      better understanding of MS pathophysiology and disease course over time. The
      conference participants concluded that evidence of new MRI gadolinium-enhancing
      (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions
      (subclinical activity, subclinical relapses) should be added to the clinical
      classification of MS in distinguishing relapsing inflammatory from progressive
      forms of the disease. The consensus was that these changes to the classification
      system would provide more rigorous definitions and categorization of MS course,
      leading to better insights as to the evolution and treatment of MS. 

PMID- 24453743
TI  - Effect of a Single Bout of Intermittent versus Continuous Walking on Perceptions
      of Fatigue in People with Multiple Sclerosis.
AB  - Fatigue may limit the ability of people with multiple sclerosis (MS) to
      participate in walking exercises, which could ultimately reduce their benefit
      from physical therapy. An exercise program that minimizes the fatigue experienced
      by people with MS during exercise may lead to an increase in the amount of
      exercise being performed. The purpose of this study was to determine whether
      subjective feelings of fatigue differ in people with MS depending on whether they
      exercised intermittently or continuously. Using a within-subjects,
      counterbalanced crossover design, a sample of 30 individuals with MS performed 6
      minutes of continuous and 6 minutes of intermittent walking 1 week apart. Fatigue
      was measured on the Visual Analogue Scale of Fatigue (VASF) and recorded before
      and after the walking conditions. A 2 * 2 repeated-measures analysis of variance
      was used to assess the potential effects of intermittent versus continuous
      walking on self-reported fatigue. A significant interaction revealed that pre
      post mean self-ratings of fatigue on the VASF increased less in the intermittent
      condition (from 37.93 mm to 44.83 mm; difference = 6.90 mm) compared with the
      continuous condition (from 34.33 mm to 54.43 mm: difference = 20.10 mm) (P <
      .001), suggesting that patients experienced less fatigue in the intermittent
      condition despite walking an equivalent total duration. The interaction effect
      was not influenced by age, gender, disease severity or duration, use of
      antispasticity medication, use of assistive devices, or mood. The results suggest
      that people with MS may be more tolerant of, and able to perform, greater amounts
      of exercise if they exercise intermittently. 

PMID- 24453744
TI  - Barriers and facilitators related to participation in aquafitness programs for
      people with multiple sclerosis: a pilot study.
AB  - Exercise and leisure activities provide physical and psychosocial benefits to
      people with multiple sclerosis (MS) and can enhance their quality of life. In
      Winnipeg, Manitoba, Canada, people with MS have reported barriers to their
      participation in local MS-specific aquafitness (AF) programs. Therefore, a formal
      exploration of the accessibility of local AF programs for people with MS was
      undertaken. The purpose of this phenomenological study was to identify factors
      that facilitate or impede participation in AF programs by individuals with MS
      living in Winnipeg. Qualitative data were collected from a total of eight
      participants through one focus group (n = 7) and one in-depth interview (n = 1).
      The sample consisted of individuals with MS who were currently participating in
      AF programming as well as those who were not. Data were audio-recorded and
      transcribed verbatim, and thematic analysis was completed. Seven themes emerged
      regarding factors affecting participation in local AF programs. Barriers to
      participation included inadequate transportation, lack of one-on-one support,
      environmental inaccessibility, and fears associated with participation in the
      programs. Facilitators of participation included a knowledgeable instructor and
      experiencing physical and psychosocial benefits from the program. Information
      from this study was used locally to advocate for people with MS in order to
      increase participation in local AF programming. 

PMID- 24453745
TI  - Relationship between expanded health belief model variables and mammography
      screening adherence in women with multiple sclerosis: a pilot study.
AB  - People with disabilities often find it more difficult to access health-care
      services than the general population, further jeopardizing their health and well
      being. The purpose of this descriptive pilot study was to explore the
      relationship between variables of the Expanded Health Belief Model (EHBM) and
      adherence to mammography screening in a sample of homebound women with MS after
      completion of a National Multiple Sclerosis Society (NMSS) intervention, known as
      the "Home-Based Health Maintenance Program for Women with MS," that was conducted
      in Allegheny County, Pennsylvania. The intervention was conducted in the
      patients' homes and included education of the women and their partners on risk
      factors for breast cancer and instruction in breast examination techniques. The
      patients were also helped to make appointments for mammograms. This study derived
      its sample from the intervention program and used data on adherence recorded by
      the NMSS. After completion of the intervention, telephone interviews were
      conducted with women who met the inclusion criteria (N = 11). Descriptive
      statistics indicate that adherence can be successfully described using variables
      of the EHBM, including perceived susceptibility, perceived severity, perceived
      benefits, and self-efficacy. The instruments chosen for the research were well
      tolerated, useful, and efficient to administer and allowed for immediate
      assessment. 

PMID- 24453748
TI  - Editorial.

PMID- 24453746
TI  - Assessing relapses and response to relapse treatment in patients with multiple
      sclerosis: a nursing perspective.
AB  - There are currently no assessment tools that focus on evaluating patients with
      multiple sclerosis (MS) who are experiencing a relapse or that evaluate patients'
      response to acute relapse treatment. In practice, assessments are often
      subjective, potentially resulting in overlooked symptoms, unaddressed patient
      concerns, unnoticed or underrecognized side effects of therapies (both disease
      modifying and symptomatic), and suboptimal therapeutic response. Systematic
      evaluation of specific symptoms and potential side effects can minimize the
      likelihood of overlooking important information. However, given the number of
      potential symptoms and adverse events that patients may experience, an exhaustive
      evaluation can be time-consuming. Clinicians are thus challenged to balance
      thoroughness with brevity. A need exists for a brief but comprehensive objective
      assessment tool that can be used in practice to 1) help clinicians assess
      patients when they present with symptoms of a relapse, and 2) evaluate outcomes
      of acute management. A working group of expert nurses convened to discuss
      recognition and management of relapses. In this article, we review data related
      to recognition and management of relapses, discuss practical challenges, and
      describe the development of an assessment questionnaire that evaluates relapse
      symptoms, the impact of symptoms on the patient, and the effectiveness and
      tolerability of acute treatment. The questionnaire is designed to be appropriate
      for use in MS specialty clinics, general neurology practices, or other practice
      settings and can be administered by nurses, physicians, other clinicians, or
      patients (self-evaluation). The relapse assessment questionnaire is currently
      being piloted in a number of practice settings. 

PMID- 24453747
TI  - Influence of occupational therapy on resilience in individuals with multiple
      sclerosis.
AB  - This quasi-experimental pilot study examined the impact of multidisciplinary
      care, with a particular focus on occupational therapy (OT), on resilience in
      individuals with multiple sclerosis (MS). Individuals with a diagnosis of MS who
      were receiving multidisciplinary care including outpatient OT at an MS center
      were invited to participate. A total of 36 individuals agreed to enroll and were
      asked to complete a demographic questionnaire and the Resilience Scale (RS).
      After an 8-week period of multidisciplinary treatment, the 35 individuals who
      completed treatment were again asked to complete the RS. As a group they
      demonstrated statistically significant improvement in resilience. A cohort of
      participants unexpectedly did not follow through with OT but did follow through
      with their other referrals. These individuals completed the RS before and after
      the 8-week time period and became an ad hoc control group. The group receiving OT
      showed significant improvement in resilience, while the control group did not.
      This study shows that a multidisciplinary approach to care, especially when it
      includes OT, is effective in treating individuals with MS. Occupational therapy
      focuses on treating symptoms that specifically limit daily functioning and
      participation, and may be uniquely positioned to affect resilience. Because
      resilience plays an important role in functional recovery and maintenance, this
      study suggests that OT may be a critical component of MS care in developing
      characteristics that enhance resilience. 

PMID- 24453749
TI  - Environmental factors affecting the daily functioning of jordanian individuals
      with multiple sclerosis.
AB  - Occupational therapists must consider the hindering and facilitating effects of
      the environment on patients' functional performance when planning therapeutic
      interventions. The purpose of this study was to explore environmental factors
      that hinder, and available services that facilitate, the daily functioning of
      Jordanian individuals with multiple sclerosis (MS) as perceived by the patients
      themselves. A sample of 103 Jordanian individuals with MS completed a
      questionnaire on hindering environmental factors and facilitative services.
      Factors and services were identified according to their description in the World
      Health Organization's International Classification of Functioning, Disability and
      Health. Environmental factors that were reported by the participants to be most
      hindering to their daily functioning were stores and malls (74.2%), noise
      (87.1%), attitudes of immediate family (52.0%), and government policies and
      regulations (52.2%). Moreover, the participants reported that psychological
      services were the least available facilitative services in the community (83.8%).
      Weak-to-moderate but significant correlations were found between a number of
      demographic variables and perceived hindering factors. The study results indicate
      that hindering factors, facilitative services, and demographic variables should
      be given greater attention by rehabilitation practitioners (especially
      occupational therapists) when planning intervention programs for Jordanian
      individuals with MS. 

PMID- 24453750
TI  - Self-reported burden among caregivers of patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) and Alzheimer's disease (AD) are chronic and progressive
      diseases that may impose a significant burden on caregivers and patients'
      immediate families. Extensive research shows MS and AD caregiver burden on
      physical and mental health, but no direct comparisons between MS and AD
      caregivers have been reported in the literature. The objective of this study was
      to examine the extent of MS caregiver burden compared with that of noncaregivers
      and AD caregivers. Data were obtained from the 2009 National Health and Wellness
      Survey administered online to a US representative adult sample (N = 75,000).
      Respondents reported health status, quality of life, work productivity, health
      care utilization, and caregiver status. Multivariable regressions, adjusting for
      key characteristics (eg, age, gender, marital status, depression), were conducted
      to explore differences between MS caregivers (n = 215) and noncaregivers (n =
      69,224) and between MS caregivers and AD caregivers (n = 1341). The results
      indicated that MS caregivers had significantly greater activity impairment (P =
      .01), poorer mental (P = .015) and physical (P = .002) health status, lower
      health utility scores (P = .002), and more traditional health-care provider
      visits (P < .001), emergency room (ER) visits (P < .001), and hospitalizations (P
      = .001) than noncaregivers, adjusting for covariates. After adjustments, MS
      caregivers had greater activity impairment (P = .044), more ER visits (P = .017),
      and more hospitalizations (P = .008) than AD caregivers. Significant work
      productivity differences were not observed across groups, possibly owing to fewer
      employed respondents. Thus, in this study, MS caregivers had significantly more
      burden than noncaregivers, and for some measures, even AD caregivers. The results
      reveal the hidden toll on those providing care for MS patients and highlight the
      need for health-care providers to recognize their burden so that appropriate
      measures can be implemented. 

PMID- 24453752
TI  - The Combined Effect of Nursing Support and Adverse Event Mitigation on Adherence
      to Interferon Beta-1b Therapy in Early Multiple Sclerosis: The START Study.
AB  - There is limited clinical evidence on the impact of nurse support and adverse
      event (AE) mitigation techniques on adherence to interferon beta-1b (IFNbeta-1b)
      therapy in multiple sclerosis (MS) in a real-world setting. The aim of the
      Success of Titration, analgesics, and BETA nurse support on Acceptance Rates in
      MS Treatment (START) trial was to assess the combined effect of titration,
      analgesics, and BETA (Betaseron Education, Training, Assistance) nurse support on
      adherence to IFNbeta-1b therapy in patients with early-onset MS and to evaluate
      safety. Participants were instructed to titrate IFNbeta-1b and use analgesics to
      minimize flu-like symptoms. All received BETA nurse follow-up at frequent
      intervals: live training, two telephone calls during the first month of therapy,
      and monthly calls thereafter. Participants were considered adherent if they took
      at least 75% of the total prescribed doses over 12 months (>=75% compliance).
      Safety was monitored via reported AEs and laboratory test results. Participants
      who took at least one IFNbeta-1b dose over 12 months were analyzed (N = 104);
      73.8% of participants completed the study. The mean age of participants was 37.2
      years; 72.1% were women and 78.8% were white. Ninety participants had relapsing
      remitting MS and 14 had clinically isolated syndrome. The mean compliance rate,
      reported for 96 participants with complete dose interruption records, was 84.4%.
      At 12 months, 78.1% of participants were considered adherent. The serious adverse
      event rate was 9.6%; most events were unrelated to therapy. Thus in the START
      study, in which participants received nursing support combined with dose
      titration and use of analgesics, the majority of participants were adherent to
      therapy. 

PMID- 24453751
TI  - Recruiting for caregiver education research: perspectives of caregivers of people
      with multiple sclerosis.
AB  - Caregiver education programs can support participants in a role that is often
      challenging. Research is needed to determine the effectiveness of these programs;
      however, recruitment for such studies can be difficult. The objectives of this
      study were to explore 1) how multiple sclerosis (MS) caregivers respond to
      recruitment materials for a research study evaluating a caregiver education
      program, including aspects of the materials that encourage or discourage their
      interest in participation; and 2) what recommendations MS caregivers have for
      improving study recruitment advertising. Qualitative interviews were conducted
      with seven MS caregivers. Participants were asked about their reactions to
      advertisements for a pilot study intended to evaluate an MS caregiver education
      program. Participants were also asked to reflect on factors that would influence
      their decision to participate in the program and to provide suggestions to
      improve recruitment materials. Data were analyzed using a constant-comparative
      approach. Study findings indicated that the language and visual design of the
      advertisements influenced the participants' initial responses. Some caregivers
      first responded to the fact that the program was part of a research study, and
      these caregivers had overall negative responses to the advertising, such as
      concern that the program was being "tested." Other caregivers first considered
      the personal relevance of the program. These caregivers had neutral-to-positive
      responses to the flyers and weighed the relevance of the program against the
      research and logistical aspects. Participants provided recommendations to improve
      the recruitment materials. While recruiting for caregiver education research can
      be challenging, piloting recruitment materials and using a variety of advertising
      options may improve response. 

PMID- 24453753
TI  - Differentiation of neuromyelitis optica from multiple sclerosis on spinal
      magnetic resonance imaging.
AB  - In order to examine the accuracy of magnetic resonance imaging (MRI)-based
      diagnosis of neuromyelitis optica (NMO) versus multiple sclerosis (MS), we
      performed a retrospective, rater-blinded review of 29 cases of NMO and 30 cases
      of MS using the criteria of long (more than three vertebral levels), continuous
      lesions with a central cord location for NMO and more peripheral and patchy
      lesions for MS. Using these criteria, two raters were able to distinguish the two
      conditions with a good degree of confidence, particularly when the imaging was
      performed at the time of an acute cord attack. The sensitivity and specificity
      for diagnosis of NMO were 86.2% and 93.3%, respectively, for Rater A and 96.4%
      and 78.6%, respectively, for Rater B, with a kappa value of 0.72. Thus there are
      significant differences in lesion characteristics that allow the distinction on
      spinal cord imaging between MS and NMO with a moderately high degree of
      confidence. The location of the lesion as evident on MRI of the spine can be
      regarded as a distinguishing diagnostic feature between MS and NMO. 

PMID- 24453755
TI  - Editorial.

PMID- 24453754
TI  - Interdisciplinary treatment of patients with multiple sclerosis and chronic pain:
      a descriptive study.
AB  - The objective of this study was to examine the efficacy of an interdisciplinary
      pain rehabilitation program in a multiple sclerosis (MS) population by evaluating
      changes in mood, pain, and functioning. This descriptive study examined 20
      patients with chronic pain and MS who were admitted to the Cleveland Clinic's
      Chronic Pain Rehabilitation Program (CPRP) between 2000 and 2009. At both
      admission to and discharge from the CPRP, measures of pain, depression, and
      functioning were obtained using a pain visual analogue scale (VAS), the Beck
      Depression Inventory (BDI), the Depression Anxiety Stress Scale (DASS), and the
      Pain Disability Index (PDI). Outcomes for the MS patients were compared with
      those of patients without MS who had participated in the same program. The
      results showed that MS patients who completed the CPRP reported dramatic
      decreases in pain and depression and an increase in daily functioning. The
      benefits received by MS patients from the program were similar to those received
      by patients without MS. Thus programs like the CPRP can result in significant
      improvements in pain, depression, and functioning among people with MS. 

PMID- 24453756
TI  - Between-rater reliability of the 6-minute walk test, berg balance scale, and
      handheld dynamometry in people with multiple sclerosis.
AB  - This study investigated the between-rater reliability of the Berg Balance Scale
      (BBS), 6-Minute Walk test (6MW), and handheld dynamometry (HHD) in people with
      multiple sclerosis (MS). Previous studies that examined BBS and 6MW reliability
      in people with MS have not used more than two raters, or analyzed different
      mobility levels separately. The reliability of HHD has not been previously
      reported for people with MS. In this study, five physical therapists assessed
      eight people with MS using the BBS, 6MW, and HHD, resulting in 12 pairs of data.
      Data were analyzed using intraclass correlation coefficients (ICCs), Spearman
      correlation coefficients (SCCs), and Bland and Altman methods. The results
      suggest excellent agreement for the BBS (SCC = 0.95, mean difference between
      raters [d] = 2.08, standard error of measurement [SEM] = 1.77) and 6MW (ICC =
      0.98, d = 5.22 m, SEM = 24.76 m) when all mobility levels are analyzed together.
      Reliability is lower in less mobile people with MS (BBS SCC = 0.6, d = -1.83; 6MW
      ICC = 0.95, d = 20.04 m). Although the ICC and SCC results for HHD suggest good
      to-excellent reliability (0.65-0.85), d ranges up to 17.83 N, with SEM values as
      high as 40.95 N. While the small sample size is a limitation of this study, the
      preliminary evidence suggests strong agreement between raters for the BBS and 6MW
      and decreased agreement between raters for people with greater mobility problems.
      The mean differences between raters for HHD are probably too high for it to be
      applied in clinical practice. 

PMID- 24453757
TI  - Clinical management of multiple sclerosis through home telehealth monitoring:
      results of a pilot project.
AB  - This study examined the feasibility of using home telehealth monitoring to
      improve clinical care and promote symptom self-management among veterans with
      multiple sclerosis (MS). This was a longitudinal cohort study linking mailed
      survey data at baseline and 6-month follow-up with information from home
      telehealth monitors. The study was conducted in two large Department of Veterans
      Affairs (VA) MS clinics in Seattle, Washington, and Washington, DC, and involved
      41 veterans with MS. The measures were demographic information and data from a
      standardized question set using a home telehealth monitor. Participants reported
      moderate levels of disability (median Expanded Disability Status Scale [EDSS]
      score, 6.5) and substantial distance from the nearest VA MS clinic (mean
      distance, 93.6 miles). Of the participants, 61.0% reported current use of MS
      disease-modifying treatments. A total of 85.4% of participants provided
      consistent data from home monitoring. Overall satisfaction with home telehealth
      monitoring was high, with 87.5% of participants rating their experience as good
      or better. The most frequently reported symptoms at month 1 were fatigue (95.1%),
      depression (78.0%), and pain (70.7%). All symptoms were reported less frequently
      by month 6, with the greatest reduction in depression (change of 23.2 percentage
      points), although these changes were not statistically significant. Home
      telehealth monitoring is a promising tool for the management of chronic disease,
      although substantial practical barriers to efficient implementation remain. 

PMID- 24453758
TI  - Psychometric properties of the modified fatigue impact scale.
AB  - Psychometric assessments are tests or questionnaires that have been designed to
      measure constructs of interest in an individual or a target population. A goal of
      many of these self-report instruments is to provide researchers with the ability
      to gather subjective information in a manner that might allow for quantitative
      analysis and interpretation of these results. This requires the instrument of
      choice to have adequate psychometric properties of reliability and validity. Much
      research has been conducted on creating self-report quality of life
      questionnaires for individuals with multiple sclerosis (MS). This article focuses
      on one in particular, the Modified Fatigue Impact Scale (MFIS). The article
      starts with a brief description of the rationale, construction, and scoring of
      the inventory. Next, the best available reliability and validity data on the MFIS
      are presented. The article concludes with a brief discussion on the
      interpretation of scores, followed by suggestions for future research. This
      summative analysis is intended to examine whether the instrument is adequately
      measuring the impact of fatigue and whether the scores allow for meaningful
      interpretations. 

PMID- 24453759
TI  - Impact of comorbidity on fatigue management intervention outcomes among people
      with multiple sclerosis: an exploratory investigation.
AB  - This exploratory secondary analysis examined whether the presence of six chronic
      health conditions moderated the effectiveness of a teleconference-delivered
      fatigue self-management education program for people with multiple sclerosis
      (MS). The longitudinal data used were from a randomized controlled trial
      involving 181 community-dwelling adults with MS. The primary outcome was fatigue
      impact, as measured by the Fatigue Impact Scale (FIS). Mixed-effects analysis of
      variance (ANOVA) models were used to determine the best-fitting model. Just under
      65% (n = 112) of participants had at least one comorbid condition. Only diabetes
      and arthritis moderated all three FIS subscales over time. People with diabetes
      were slower to show improvement after intervention than people without diabetes.
      People with arthritis made much more dramatic initial gains compared with people
      without arthritis but had difficulty maintaining those gains over time. The
      results point to the need for greater attention to the impact of comorbidities on
      rehabilitation interventions. These exploratory findings suggest that fatigue
      self-management education protocols may need to be customized to people who are
      trying to incorporate MS fatigue self-management behaviors while simultaneously
      managing diabetes or arthritis. 

PMID- 24453760
TI  - Effectiveness of a relationship enrichment program for couples living with
      multiple sclerosis.
AB  - Living with a chronic illness such as multiple sclerosis (MS) has significant
      psychosocial ramifications. In particular, the patient's relationship with a
      spouse or significant other is often negatively affected. Programs are needed to
      address the psychosocial challenges of the illness and help improve outcomes for
      both the person with MS and his or her romantic support partner. Relationship
      Matters (RM) is a relationship enrichment program that integrates information and
      resources of the National Multiple Sclerosis Society with empirically based
      marriage education. The purpose of this study was to examine the effectiveness of
      the RM program in increasing relationship satisfaction and aspects of health
      related quality of life in couples living with MS over a 3-month follow-up
      period. Couples were given 8 hours of programming via in-person workshops
      disseminated across the country or teleconferences. A control group consisting of
      members of MS couples who did not receive the intervention was used for
      comparison. The results indicate that RM significantly improved relationship
      satisfaction over time compared with no intervention (P < .05). Additional
      findings include significant improvements in mental health-related quality of
      life as well as reported improvements in communication, conflict resolution, and
      ability to handle MS-specific relationship issues. Overall, these findings show
      that RM results in improved couple functioning and additional psychological
      health benefits for individuals with MS and their romantic support partners. 

PMID- 24453761
TI  - Facilitating medication adherence in patients with multiple sclerosis.
AB  - This article reviews adherence to medication in multiple sclerosis (MS) patients
      from the perspective of nurse and social worker authors. It reviews data on
      patient adherence and offers practical, evidence-based strategies that health
      care providers can use to facilitate adherence. In addition, it examines how
      emerging MS therapies may affect patient adherence and associated interventions.
      To promote adherence, interventions need to incorporate new and creative
      approaches. A proactive approach includes assessing patient needs and lifestyle
      before the start of medication and selecting the most appropriate disease
      modifying therapy for each individual patient. Including multidisciplinary
      expertise and services in the treatment plan can be part of a comprehensive,
      holistic approach to helping patients and families. Optimization of health-care
      provider roles is likely to facilitate improved adherence. 

PMID- 24453763
TI  - Editorial.

PMID- 24453762
TI  - Change in the Health-Related Quality of Life of Multiple Sclerosis Patients over
      5 Years.
AB  - This study examined whether multiple sclerosis (MS) patients (N = 3779)
      experience change in their perceived health-related quality of life (HRQOL) over
      a 5-year period, and investigated baseline factors that may be related to change
      in HRQOL. Data from the North American Research Committee on Multiple Sclerosis
      (NARCOMS) Registry were used to address the study's research questions. Results
      for the physical and mental component scores of the 12-item Short Form Health
      Status Survey, version 2 (SF-12v2), indicated that most of the MS sample
      experienced no significant changes over a 5-year period. However, 40% and 36% of
      the sample experienced clinically significant declines in their physical and
      mental HRQOL, respectively, over the 5-year period. After controlling for
      baseline scores, having a lower education, having greater duration since disease
      diagnosis, not being employed, having a lower income, not receiving a disease
      modifying therapy, and taking a greater number of prescription medications were
      significantly associated with a clinically significant decline in physical HRQOL.
      After controlling for baseline scores, not being married/partnered, experiencing
      a greater number of relapses, not being employed, having a lower income, and
      taking a greater number of prescription medications were significantly associated
      with a clinically significant decline in mental HRQOL. Overall, most of the MS
      sample remained stable in their HRQOL over time. However, approximately four out
      of every ten patients experienced a clinically important decline in their HRQOL.
      While the association was statistically significant, the sociodemographic and
      disease-related factors linked with decline did not strongly predict decline over
      a 5-year period. 

PMID- 24453764
TI  - The need for mental health care among informal caregivers assisting people with
      multiple sclerosis.
AB  - The objective of this study was to identify characteristics of informal
      caregivers and people with multiple sclerosis (MS) receiving assistance that are
      associated with the caregiver's perceived need for mental health care. Survey
      data were collected in interviews with 530 caregivers and analyzed using a
      logistic regression model. We found that older caregiver age significantly
      decreased the odds of caregivers' perceived need for mental health treatment.
      Better mental health domains of health-related quality of life among caregivers,
      as measured by the 8-item Short Form Health Status Survey (SF-8), also were
      associated with decreased odds of the need for mental health care. In contrast,
      the caregiver's feeling that providing assistance was emotionally draining or the
      belief that this assistance threatened the caregiver/care recipient relationship
      significantly increased the odds of caregivers' needing mental health treatment.
      Health professionals treating informal caregivers should be sensitive to the
      impact that providing assistance has on the emotions, relationships, and mental
      health needs of caregivers. 

PMID- 24453765
TI  - Advances in the management of neurogenic detrusor overactivity in multiple
      sclerosis.
AB  - Bladder dysfunction in multiple sclerosis (MS) can be socially disabling, have
      negative psychological and economic consequences, and impair patients' quality of
      life. Knowledge of the functional anatomy and physiology of the urinary tract is
      essential to understand the symptoms associated with central nervous system
      lesions and the pharmacotherapies used to treat them. Treatments for neurogenic
      detrusor overactivity (NDO) have consisted mainly of administration of
      anticholinergic drugs, which have been shown to provide suboptimal clinical
      benefits and be poorly tolerated. The US Food and Drug Administration (FDA)
      approval of intravesicular botulinum toxin therapy provides a second-line option
      for MS patients with NDO not responsive to anticholinergic drugs. We performed a
      review of key literature pertaining to the intravesicular application of
      botulinum toxin. In the management of NDO, administration of intravesicular
      botulinum toxin using clean intermittent catheterization decreases the incidence
      of urinary tract infections, promotes urinary continence, and improves quality of
      life for 9 months after a single injection; moreover, those benefits are
      maintained with repeated injections over time. 

PMID- 24453766
TI  - Headache in multiple sclerosis: features and implications for disease management.
AB  - The aim of this study was to investigate the variables affecting headache
      occurrence in patients with multiple sclerosis (MS). Seventy-two MS patients with
      comorbid headaches completed a 28-item questionnaire. This evaluation assessed
      each patient's demographics, headache description and modifying factors, social
      history, and impact on quality of life. Our patients reported a wide spectrum of
      headache presentations, characteristics, and resulting disability. We discuss the
      patterns in our data in the context of current hypotheses regarding headache and
      MS causality. In our patients, migraines with aura strongly correlated with MS
      exacerbations, suggesting that they might be useful as a marker for flare-up
      onset. Patients' pain descriptions varied based on their headache frequency,
      history, and relationship to MS progression. Due to the severity of headache in
      MS patients and resulting impact on their activities of daily living, a thorough
      analysis of headache presentation is warranted in such patients. 

PMID- 24453767
TI  - Attributional style and depression in multiple sclerosis: the learned
      helplessness model.
AB  - Several etiologic theories have been proposed to explain depression in the
      general population. Studying these models and modifying them for use in the
      multiple sclerosis (MS) population may allow us to better understand depression
      in MS. According to the reformulated learned helplessness (LH) theory,
      individuals who attribute negative events to internal, stable, and global causes
      are more vulnerable to depression. This study differentiated attributional style
      that was or was not related to MS in 52 patients with MS to test the LH theory in
      this population and to determine possible differences between illness-related and
      non-illness-related attributions. Patients were administered measures of
      attributional style, daily stressors, disability, and depressive symptoms.
      Participants were more likely to list non-MS-related than MS-related causes of
      negative events on the Attributional Style Questionnaire (ASQ), and more-disabled
      participants listed significantly more MS-related causes than did less-disabled
      individuals. Non-MS-related attributional style correlated with stress and
      depressive symptoms, but MS-related attributional style did not correlate with
      disability or depressive symptoms. Stress mediated the effect of non-MS-related
      attributional style on depressive symptoms. These results suggest that, although
      attributional style appears to be an important construct in MS, it does not seem
      to be related directly to depressive symptoms; rather, it is related to more
      perceived stress, which in turn is related to increased depressive symptoms. 

PMID- 24453768
TI  - Longitudinal changes in quality of life and related psychosocial variables in
      australians with multiple sclerosis.
AB  - This study explored changes in quality of life (QOL) and psychosocial variables
      in a large cohort of people with multiple sclerosis (MS). A total of 1287
      Australians with MS were administered self-report questionnaires at baseline and
      24 months later to examine the impact of disease severity and duration, perceived
      stress, self-efficacy, depression, and social support on QOL and self-care. Over
      the 2-year survey period, MS remained stable for 70% of respondents. Disease
      severity correlated with social support at baseline but not at 24 months, when
      the only significant correlation with disease severity was that of the World
      Health Organization Quality of Life-100 instrument (WHOQOL-100) domain of Level
      of Independence. Although QOL improved across the WHOQOL-100 domains Physical,
      Psychological, Level of Independence, Social Relationships, and Environment,
      decreases were found in the WHOQOL-100 facet overall QOL and well-being as well
      as self-efficacy over the same time period. Hierarchical multiple regression was
      used to assess the utility of four control measures. MS disease severity and MS
      disease duration were entered at Step 1, explaining 16.1% of the variance in QOL.
      After entry of perceived stress, self-efficacy, social support, and the
      Depression, Anxiety and Stress Scale-21 (DASS-21) at Step 2, the total variance
      explained by the model as a whole was 55.8% (F6,1028 = 216.495, P < .001). Thus,
      even in the presence of stable disease and improvement in some WHOQOL-100
      domains, overall QOL and self-efficacy had decreased at 2 years after the
      collection of baseline data. Loss of self-efficacy, increased stress, and
      depression are key factors in reduced QOL in people with MS. 

PMID- 24453770
TI  - Editorial.

PMID- 24453771
TI  - New IJMSC Online Edition Marks First Anniversary.

PMID- 24453769
TI  - Self-management for people with multiple sclerosis: report from the first
      international consensus conference, november 15, 2010.
AB  - People with multiple sclerosis (MS) must manage the day-to-day effects of the
      disease on their lives. Self-management interventions may be helpful in this
      challenge. An international, multidisciplinary consensus conference was held on
      November 15, 2010, by the University of Washington's Rehabilitation Research and
      Training Center for Multiple Sclerosis (MS RRTC), with funding from the
      Consortium of Multiple Sclerosis Centers (CMSC) and the National Institute on
      Disability and Rehabilitation Research (NIDRR), to discuss the concept of self
      management for people with MS. The specific goals of the consensus conference
      were as follows: 1) review the current research on self-management and related
      issues in chronic disability and specifically in MS; 2) review optimal research
      methodologies, outcome measurement tools, program planning frameworks, and
      dissemination strategies for self-management research; and 3) establish
      recommendations on the next steps necessary to develop, adapt, and test self
      management interventions for people with MS. The consensus conference and this
      document are the initial steps toward achieving the stated goals. Participants in
      the consensus conference concluded that it is necessary to: 1) define an
      empirically based conceptual model of self-management for people with MS; 2)
      establish reliable and valid self-management outcome measures; 3) use best
      practices to validate models of self-management interventions; and 4) plan
      dissemination and knowledge translation of interventions once their effectiveness
      is established. 

PMID- 24453772
TI  - Relationship between disease-modifying therapy and depression in multiple
      sclerosis.
AB  - Many prescribers of disease-modifying therapies (DMTs) for multiple sclerosis
      (MS) believe that interferon beta (IFNbeta) is more likely than glatiramer
      acetate (GA) to increase depression during the course of MS treatment. Therefore,
      newly diagnosed patients with a history of depression are often placed on GA
      therapy from the onset of MS treatment. The aim of this study was to examine the
      relationship between DMT type and depression among patients with relapsing
      remitting MS (RRMS). Patients with RRMS who were examined from 2000 to 2007 and
      who remained on a single course of therapy (either an IFNbeta or GA) were
      included in a retrospective review of medical records. Patients were asked to
      complete the Beck Depression Inventory (BDI) at treatment initiation and every 6
      months thereafter for up to 4 years. Only patients who had completed a BDI within
      6 weeks of starting their DMT were included in the analysis. No significant
      differences in mean change in BDI score were observed from baseline to 48 months
      between the IFNbeta and GA subgroups. Additionally, no significant differences in
      mean BDI score change were observed between antidepressant-treated and non
      antidepressant-treated patients within the IFNbeta or GA subgroup. Neither
      IFNbeta nor GA therapy appears to exacerbate depressive symptoms in patients with
      RRMS who remain on their initial therapy. 

PMID- 24453773
TI  - The incidence and prevalence of neuromyelitis optica: a systematic review.
AB  - Interest in neuromyelitis optica (NMO) has increased substantially over the last
      few years, but it is not known whether NMO has the same geographic and temporal
      variations in disease risk as multiple sclerosis (MS). We aimed to evaluate the
      worldwide incidence and prevalence of NMO through a systematic review of
      published peer-reviewed studies. We performed a search of the English-language
      literature using MEDLINE and EMBASE from January 1985 to March 2012. Search terms
      included "neuromyelitis optica," "Devic's," "opticospinal," "incidence,"
      "prevalence," and "epidemiology." We assessed study quality using a standardized
      instrument. A total of five studies met the inclusion criteria. Three of the
      studies were from North America, and all studies were published between 2005 and
      2012. All studies were of good quality, but only one study reported standardized
      rates, and subgroup-specific estimates were rarely reported. The incidence of NMO
      per 100,000 population ranged from 0.053 to 0.40, while the prevalence per
      100,000 population ranged from 0.52 to 4.4. Heterogeneity was high among the
      incidence (I(2) = 68.0%) and prevalence studies (I(2) = 94.0%). This review
      highlights the limited knowledge regarding the epidemiology of NMO and the
      importance of obtaining estimates standardized to common populations to enhance
      comparability of studies from different jurisdictions. Future studies would also
      benefit from reporting age-, sex-, and race- or ethnicity-specific estimates. 

PMID- 24453774
TI  - Changes in Fatigue and Cognition in Patients with Relapsing Forms of Multiple
      Sclerosis Treated with Natalizumab: The ENER-G Study.
AB  - Fatigue and cognitive impairment are debilitating features of multiple sclerosis
      (MS). ENER-G was a 12-month, open-label, multicenter, single-arm observational
      study designed to evaluate changes in fatigue and cognition in MS patients
      treated with natalizumab. Adults with relapsing MS and initiating natalizumab
      were enrolled. The primary endpoint was change in Visual Analog Scale for Fatigue
      (VAS-F) score over 12 weeks. Changes in Modified Fatigue Impact Scale (MFIS)
      score, Fatigue Severity Scale (FSS) score, and cognitive performance, using
      Automated Neuropsychological Assessment Metrics (ANAM), were also assessed.
      Patients (N = 89) had a mean age of 41 years and a median Expanded Disability
      Status Scale score of 3.0, and 83% had used at least two prior MS therapies.
      Significant improvements were observed and maintained at 12 weeks in VAS-F (mean
      +/- SD baseline score, 77.7 +/- 10.2; mean +/- SD change, -14.9 +/- 17.1; P <
      .0001), MFIS (mean baseline score, 59.1 +/- 12.2; mean change, -7.4 +/- 11.8; P <
      .0001), and FSS (median baseline score, 6.3 [range, 3.9-7.0]; median change, -0.4
      [range, -2.9-1.4]; P < .0001). Cognitive performance remained stable or improved
      (depending on the ANAM measure). Thus significant improvements in fatigue were
      maintained over time, and cognitive performance improved or remained stable up to
      48 weeks after initiation of natalizumab in MS patients with some degree of
      fatigue. 

PMID- 24453775
TI  - "Her illness is a project we can work on together": developing a collaborative
      family-centered intervention model for newly diagnosed multiple sclerosis.
AB  - This article presents a model for intervening with families that are addressing a
      new diagnosis of multiple sclerosis (MS) in one member. The model is
      collaborative, integrative, and family-centered. It involves both working with
      the family collaboratively and providing strategies to promote greater
      collaboration within the family. The model integrates elements of crisis
      intervention theory, psycho-education, and family-centered approaches. The model
      was developed with families addressing MS, and was piloted with three families.
      The intervention was found to improve family members' ability to collaborate with
      each other. Such increased collaboration may enhance the family's ability to
      manage long-term illness more effectively, help the family address the impact of
      the illness on all family members, and generally improve the family's quality of
      life. 

PMID- 24453776
TI  - Aerobic exercise in people with multiple sclerosis: its feasibility and secondary
      benefits.
AB  - The aims of this study were to explore the feasibility of structured aerobic
      exercise followed by a period of unstructured physical activity and determine the
      impact of such exercise on cognition, mood, and quality of life in people with
      multiple sclerosis (MS). A convenience sample of 9 individuals with relapsing
      remitting MS performed 30 minutes of aerobic exercise (upper- and lower-extremity
      ergometry and treadmill ambulation) twice weekly for 8 weeks, followed by 3
      months of unstructured physical activity. Eight participants completed the
      intervention and posttest; 6 returned for the 3-month follow-up. Cardiovascular
      fitness, cognition, mood (measured with the Beck Depression Inventory-II; BDI
      II), and quality of life (measured with the Multiple Sclerosis Quality of Life
      54; MSQOL-54) were assessed. Participants completed 27.9 minutes of exercise per
      session, with an 85.1% attendance rate. Evaluation using the Wilcoxon signed rank
      test revealed no deleterious effects and improved results on the BDI-II and MSQOL
      54 mental subscale. Analysis of change scores using the one-sample t test
      revealed that the BDI-II and MSQOL-54 were changed from zero after structured
      exercise, but only the BDI-II maintained improvement after unstructured physical
      activity. Further analysis of BDI-II subscales revealed that improvement occurred
      only in the Somato-Affective subscale. In this study, program feasibility was
      demonstrated in several ways. There were no declines in cognitive function over
      the 5-month period. Despite unchanged cognitive function, participants may value
      the improved mood enough to continue both the structured and unstructured
      physical activity. The role of unstructured physical activity in concert with
      periodic structured exercise programs merits further investigation. 

PMID- 24453777
TI  - Natural history of multiple sclerosis symptoms.
AB  - The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is
      a database that contains information from over 35,000 patient volunteers on
      symptom severity in 11 domains commonly affected in multiple sclerosis (MS):
      mobility, hand function, vision, fatigue, cognition, bowel/bladder function,
      sensory, spasticity, pain, depression, and tremor/coordination. The Registry
      affords a unique opportunity to study the frequency and severity of domain
      specific impairment in a contemporary, mostly treated MS cohort over the course
      of the disease. The objective of this work was to calculate symptom prevalence in
      each of the 11 domains for years 0 to 30 from symptom onset. The resulting
      "symptom prevalence tables" demonstrate that a majority of participants perceive
      at least some degree of impairment in most domains as early as the first year of
      disease. The severity of impairment increases with disease duration across all
      domains, but the patterns of disability accumulation differ. The symptom
      prevalence tables illustrate the magnitude of perceived impact of the disease and
      highlight the extent of unmet need in symptomatic management. The tables are easy
      to use and allow MS patients and their clinicians to compare an individual's own
      impairment in any of the 11 domains to that of NARCOMS participants with the same
      disease duration. 

PMID- 24453778
TI  - Editorial.

PMID- 24453779
TI  - Efficacy and safety of alemtuzumab in multiple sclerosis and impact on nursing
      role.
AB  - Alemtuzumab, a humanized monoclonal antibody, has shown efficacy for relapsing
      remitting multiple sclerosis (MS) in phase 2 and phase 3 trials. Compared with
      subcutaneous interferon beta-1a, alemtuzumab significantly reduced the risk for
      accumulation of disability and the rate of relapse, and improved mean disability
      level from baseline. Notable safety and tolerability concerns include infusion
      associated reactions, infections of predominantly mild-to-moderate severity, and
      autoimmune adverse events, principally thyroid disorders and immune
      thrombocytopenia. As emerging therapies such as alemtuzumab are approved for the
      treatment of MS, nurses specializing in the care of MS patients will make
      increasingly significant contributions to the education of patients, caregivers,
      and other health-care providers about these therapies' efficacy, tolerability,
      safety, and administration. This article reviews the phase 2 and phase 3 efficacy
      and safety results for alemtuzumab, with an emphasis on the role of nurses in
      communication about this treatment option for those with MS. 

PMID- 24453780
TI  - Determining the Presence of Reliable Change over Time in Multiple Sclerosis:
      Evidence from the PASAT, Adjusting-PSAT, and Stroop Test.
AB  - People with multiple sclerosis (MS) often undergo repeated assessments. Methods
      for determining whether an individual's change in test results over time is
      reliable require further study. A sample of individuals with MS (N = 52) was
      assessed at baseline and at 6-month follow-up using the Paced Auditory Serial
      Addition Test (PASAT), Simple Adjusting-Paced Serial Addition Test (A-PSAT), and
      Victoria Stroop test. Two methods for determining the reliability of an
      individual's change over time were examined. The Reliable Change Index (RCI)
      identified few individuals who declined reliably between baseline and 6-month
      follow-up. The standard deviation (SD) method of calculation resulted in reliable
      declines for a small number of individuals on most measures. Use of the SD method
      resulted in a larger number of individuals who improved reliably. Responsiveness
      of individuals to treatment effects can be lost in group analyses. The data
      presented here provide clinicians with an approach for determining whether an
      individual's change over time on commonly used neuropsychological tests reflects
      reliable improvement or decline. 

PMID- 24453781
TI  - Poster abstracts from the third international symposium on gait and balance in
      multiple sclerosis: selecting the right measures.

PMID- 24453782
TI  - Development and validation of the actionable bladder symptom screening tool for
      multiple sclerosis patients.
AB  - Bladder symptoms such as urinary urgency, frequency, and incontinence are common
      in people with multiple sclerosis (MS). These symptoms, which often result from
      neurogenic detrusor overactivity (NDO), can have a major impact on patients' day
      to-day lives. However, in many cases they are over-looked in the clinical
      management of MS. The objective of this study was to develop and validate a
      reliable, sensitive, and specific screening tool for patients with bladder
      problems related to MS. We performed a literature review and then conducted a
      content validation study followed by a multisite observational study of a new
      screening tool, the Actionable Bladder Symptom Screening Tool (ABSST). All ABSST
      domains as well as the total score met the threshold for good internal
      consistency (Cronbach alpha >= 0.70), with a Cronbach alpha value of 0.95 for the
      total score and values ranging from 0.85 to 0.90 for the three domains. The
      validity of the ABSST was demonstrated by high correlation of the domains and
      total score with the Overactive Bladder Questionnaire Short Form (OAB-q SF)
      Symptom Severity and Total Health-Related Quality of Life (HRQOL) scores
      (Spearman correlation coefficient >= 0.782). The predictive validity of the ABSST
      total score to identify patients who might receive a recommendation to see a
      urologist was strong. This new instrument, which was developed with input from
      clinicians as well as MS patients, meets the current content validity and
      psychometric testing thresholds established by the US Food and Drug
      Administration, with high sensitivity and specificity. 

PMID- 24453783
TI  - Treatment discontinuation and disease progression with injectable disease
      modifying therapies: findings from the north american research committee on
      multiple sclerosis database.
AB  - Injectable first-line disease-modifying therapies (DMTs) for multiple sclerosis
      (MS) are generally prescribed for continuous use. Accordingly, the various
      factors that influence patient persistence with treatment and that can lead some
      patients to switch medications or discontinue treatment may affect clinical
      outcomes. Using data from the North American Research Committee on Multiple
      Sclerosis (NARCOMS) database, this study evaluated participants' reasons for
      discontinuation of injectable DMTs as well as the relationship between staying on
      therapy and sustained patient-reported disease progression and annualized relapse
      rates. Participants selected their reason(s) for discontinuation from among 16
      possible options covering the categories of efficacy, safety, tolerability, and
      burden, with multiple responses permitted. Both unadjusted data and data adjusted
      for baseline age, disease duration, disability, and sex were evaluated.
      Discontinuation profiles varied among DMTs. Participants on intramuscular
      interferon beta-1a (IM IFNbeta-1a) and glatiramer acetate (GA) reported the
      fewest discontinuations based on safety concerns, although GA was associated with
      reports of higher burden and lower efficacy than other therapies. Difficulties
      with tolerability were more often reported as a reason for discontinuing
      subcutaneous (SC) IFNbeta-1a than as a reason for discontinuing IM IFNbeta-1a,
      GA, or SC IFNbeta-1b. In the persistent therapy cohort, less patient-reported
      disability progression was reported with IM IFNbeta-1a treatment than with SC
      IFNbeta-1a, IFNbeta-1b, or GA. These findings have relevance to clinical decision
      making and medication compliance in MS patient care. 

PMID- 24453784
TI  - Factors affecting employment among informal caregivers assisting people with
      multiple sclerosis.
AB  - The objective of this study was to identify characteristics of informal
      caregivers, caregiving, and the people with multiple sclerosis (MS) receiving
      assistance that are associated with reduced caregiver employment. Data were
      collected during telephone interviews with 530 MS caregivers, including 215
      employed caregivers, with these survey data analyzed using logistic regression.
      Poorer cognitive ability by the care recipient to make decisions about daily
      tasks and more caregiving hours per week predicted reduced caregiver employment.
      Better physical health domains of caregiver quality of life were associated with
      significantly lower odds of reduced employment. Health professionals treating
      informal caregivers, as well as those treating people with MS, need to be aware
      of respite, support, and intervention programs available to MS caregivers and
      refer them to these programs, which could reduce the negative impact of
      caregiving on employment. 

PMID- 24453785
TI  - Editorial.

PMID- 24453786
TI  - Longitudinal growth and body composition of twins versus singletons in the first
      month of life.
AB  - BACKGROUND: Although twin gestation is well recognized to be associated with
      impaired fetal and postnatal growth, specific data about body composition of
      twins in the first month of life are scarce. OBJECTIVE: The aim of this study was
      to compare the body composition of twins, evaluated with air-displacement
      plethysmography, to that of singletons of similar gestational age and adequacy of
      growth, during the first month of life. We tested the hypothesis that the quality
      of growth would be similar. METHODS: Anthropometric and air-displacement
      plethysmography measurements were performed in 18 pairs of twins and in 36
      singleton neonates, longitudinally, from birth to the 30th day of life. Each twin
      was matched to a singleton infant of similar gestational age and birth weight z
      score. RESULTS: With regard to anthropometric measures, the only difference was a
      lower weight in twins versus singletons on the 15th day of life. With regard to
      body composition, we did not find any difference between groups at any time
      point. Fat mass increased significantly from day 1 to day 30 in both twins and
      singletons. CONCLUSION: In terms of body composition, twins do not differ from
      singletons of similar gestational age and weight, either at birth or in early
      postnatal life.

PMID- 24453787
TI  - Design and functional testing of a multichamber perfusion platform for three
      dimensional scaffolds.
AB  - Perfusion culture systems are widely used in tissue engineering applications for
      enhancing cell culture viability in the core of three-dimensional scaffolds. In
      this work, we present a multichamber confined-flow perfusion system, designed to
      provide a straightforward platform for three-dimensional dynamic cell cultures.
      The device comprises 6 culture chambers allowing independent and simultaneous
      experiments in controlled conditions. Each chamber consists of three parts: a
      housing, a deformable scaffold-holder cartridge, and a 7 mL reservoir, which
      couples water-tightly with the housing compressing the cartridge. Short-term
      dynamic cell seeding experiments were carried out with MC3T3-E1 cells seeded into
      polycaprolactone porous scaffolds. Preliminary results revealed that the
      application of flow perfusion through the scaffold favored the penetration of the
      cells to its interior, producing a more homogeneous distribution of cells with
      respect to dropwise or injection seeding methods. The culture chamber layout was
      conceived with the aim of simplifying the user operations under laminar flow hood
      and minimizing the risks for contamination during handling and operation.
      Furthermore, a compact size, a small number of components, and the use of bayonet
      couplings ensured a simple, fast, and sterility-promoting assembling. Finally,
      preliminary in vitro tests proved the efficacy of the system in enhancing cell
      seeding efficiency, opening the way for further studies addressing long-term
      scaffold colonization.

PMID- 24453788
TI  - Periodontal care as a fundamental step for an active and healthy ageing.
AB  - In the industrialized part of the world, an increasing number of people live the
      old age without too many restrictions due to illness or physiological impairment.
      This group is known as the young elderly. On the contrary, a consistent part of
      seniors develops a greater number of medical conditions and become more and more
      dependent, these are the old elderly. The first cause of tooth lost in
      industrialized word is periodontitis that generally strikes people older than 40
      years and determines serious detriment of the stomatognatic organ. Smoking and
      stress are risk factors for periodontitis that are common and shared between
      young, adult, and older age. Diabetes mellitus, obesity, and osteoporosis are
      very frequent pathological situations in older age. They have been identified as
      cofactors in the progression of periodontitis. Many dental associations recognize
      the importance of continued research on oral fluids diagnostics and welcome the
      development of rapid point-of-care tests providing accurate measurements of
      clinically validated biomarkers. At present, well-studied molecules associated
      with host response factors and with derived tissue destruction mediators have
      been proposed as diagnostic biomarkers for periodontitis detected in the oral
      fluids. 

PMID- 24453789
TI  - Antioxidant characterization of oak extracts combining spectrophotometric assays
      and chemometrics.
AB  - Antioxidant characteristics of leaves, twigs, and acorns from two Serbian oak
      species Quercus robur L. and Quercus petraea L. from Vojvodina province (northern
      Serbia) were investigated. 80% ethanol (in water) extracts were used for
      antiradical power (ARP) determinations against DPPH(*), (*)NO, and O2 (*-)
      radicals, ferric reducing antioxidant power (FRAP), total phenol, tannin,
      flavonoid, and proanthocyanidin contents. Permanganate reducing antioxidant
      capacity (PRAC) was determined using water extracts. Beside, mentioned
      parameters, soluble proteins, lipid peroxidation (LP), pigments and proline
      contents were also determined. The data of different procedures were compared and
      analyzed by multivariate techniques (correlation matrix calculation and principal
      component analysis (PCA)). PCA found that investigated organs of two different
      oak tree species possess similar antioxidant characteristics. The superior
      antioxidant characteristics showed oak leaves over twigs and acorns and seem to
      be promising source of antioxidants with possible use in industry and pharmacy. 

PMID- 24453790
TI  - Periprosthetic joint infection: clinical and bench.

PMID- 24453791
TI  - Design of an efficient real-time algorithm using reduced feature dimension for
      recognition of speed limit signs.
AB  - We propose a real-time algorithm for recognition of speed limit signs from a
      moving vehicle. Linear Discriminant Analysis (LDA) required for classification is
      performed by using Discrete Cosine Transform (DCT) coefficients. To reduce
      feature dimension in LDA, DCT coefficients are selected by a devised discriminant
      function derived from information obtained by training. Binarization and thinning
      are performed on a Region of Interest (ROI) obtained by preprocessing a detected
      ROI prior to DCT for further reduction of computation time in DCT. This process
      is performed on a sequence of image frames to increase the hit rate of
      recognition. Experimental results show that arithmetic operations are reduced by
      about 60%, while hit rates reach about 100% compared to previous works. 

PMID- 24453792
TI  - Derivation of probability density function of signal-to-interference-plus-noise
      ratio for the MS-to-MS interference analysis.
AB  - This paper provides an analytical derivation of the probability density function
      of signal-to-interference-plus-noise ratio in the scenario where mobile stations
      interfere with each other. This analysis considers cochannel interference and
      adjacent channel interference. This could also remove the need for Monte Carlo
      simulations when evaluating the interference effect between mobile stations.
      Numerical verification shows that the analytical result agrees well with a Monte
      Carlo simulation. Also, we applied analytical methods for evaluating the
      interference effect between mobile stations using adjacent frequency bands. The
      analytical derivation of the probability density function can be used to provide
      the technical criteria for sharing a frequency band. 

PMID- 24453793
TI  - Is all human hearing cochlear?
AB  - The objective of this cross-sectional study was to investigate the possibility
      that the saccule may contribute to human hearing. The forty participants included
      twenty healthy people and twenty other subjects selected from patients who
      presented with benign paroxysmal positional vertigo to Audiology Department of
      Hazrat Rasoul Akram hospital (Tehran, Iran). Assessments comprised of
      audiological evaluations, cervical vestibular evoked myogenic potentials
      (cVEMPs), recognition of spoken phonemes in white noise (Rsp in wn), and auditory
      brainstem response to 500 Hz tone burst (ABR(500 HZ)). Twenty affected ears with
      decreased vestibular excitability as detected by abnormal cVEMPs revealed
      decreased scores of Rsp in wn and abnormal findings of ABR(500 HZ). Both
      unaffected and normal ears had normal results. Multiple comparisons of mean
      values of cVEMPs and ABR(500 HZ) between three groups were significant (P < 0.05,
      ANOVA). The correlation between RSP in wn and p13 latencies was significant. The
      peak-to-peak amplitudes showed significant correlation to RSP in wn. The
      correlation between RSP in wn and the latencies of n23 was significant. In high
      level of noisy competing situations, healthy human saccular sensation can mediate
      the detection of low frequencies and possibly help in cochlear hearing for
      frequency and intensity discrimination. So, all human hearing is not cochlear.

PMID- 24453794
TI  - Telomere length in elderly Caucasians weakly correlates with blood cell counts.
AB  - BACKGROUND: Age-related decrease in bone marrow erythropoietic capacity is often
      accompanied by the telomere length shortening in peripheral white blood cells.
      However, limited and conflicting data hamper the conclusive opinion regarding
      this relationship. Therefore, the aim of this study was to assess an association
      between telomere length and peripheral blood cell count parameters in the Polish
      elderly population. MATERIAL AND METHODS: The substudy included 1573 of 4981
      subjects aged 65 years or over, participants of the population-based PolSenior
      study. High-molecular-weight DNA was isolated from blood mononuclear cells.
      Telomere length (TL) was measured by QRT-PCR as abundance of telomere template
      versus a single gene copy encoding acidic ribosomal phosphoprotein P0. RESULTS:
      Only white blood count (WBC) was significantly different in TL tertile subgroups
      in all subjects (P = 0.02) and in men (P = 0.01), but not in women. Merely in men
      significant but weak positive correlations were found between TL and WBC (r =
      0.11, P < 0.05) and RBC (r = 0.08, P < 0.05). The multiple regression analysis
      models confirmed a weak, independent contribution of TL to both RBC and WBC.
      CONCLUSIONS: In the elderly, telomere shortening limits hematopoiesis capacity to
      a very limited extent.

PMID- 24453795
TI  - Development and interpretation of new sediment rating curve considering the
      effect of vegetation cover for Asian basins.
AB  - Suspended sediment concentration of a river can provide very important
      perspective on erosion or soil loss of one river basin ecosystem. The changes of
      land use and land cover, such as deforestation or afforestation, affect sediment
      yield process of a catchment through changing the hydrological cycle of the area.
      A sediment rating curve can describe the average relation between discharge and
      suspended sediment concentration for a certain location. However, the sediment
      load of a river is likely to be undersimulated from water discharge using least
      squares regression of log-transformed variables and the sediment rating curve
      does not consider temporal changes of vegetation cover. The Normalized Difference
      Vegetation Index (NDVI) can well be used to analyze the status of the vegetation
      cover well. Thus long time monthly NDVI data was used to detect vegetation change
      in the past 19 years in this study. Then monthly suspended sediment concentration
      and discharge from 1988 to 2006 in Laichau station were used to develop one new
      sediment rating curve and were validated in other Asian basins. The new sediment
      model can describe the relationship among sediment yield, streamflow, and
      vegetation cover, which can be the basis for soil conservation and sustainable
      ecosystem management. 

PMID- 24453797
TI  - Cayley bipolar fuzzy graphs.
AB  - We introduce the concept of Cayley bipolar fuzzy graphs and investigate some of
      their properties. We present some interesting properties of bipolar fuzzy graphs
      in terms of algebraic structures. We also discuss connectedness in Cayley bipolar
      fuzzy graphs. 

PMID- 24453796
TI  - Tissue engineering of urinary bladder and urethra: advances from bench to
      patients.
AB  - Urinary tract is subjected to many varieties of pathologies since birth including
      congenital anomalies, trauma, inflammatory lesions, and malignancy. These
      diseases necessitate the replacement of involved organs and tissues. Shortage of
      organ donation, problems of immunosuppression, and complications associated with
      the use of nonnative tissues have urged clinicians and scientists to investigate
      new therapies, namely, tissue engineering. Tissue engineering follows principles
      of cell transplantation, materials science, and engineering. Epithelial and
      muscle cells can be harvested and used for reconstruction of the engineered
      grafts. These cells must be delivered in a well-organized and differentiated
      condition because water-seal epithelium and well-oriented muscle layer are needed
      for proper function of the substitute tissues. Synthetic or natural scaffolds
      have been used for engineering lower urinary tract. Harnessing autologous cells
      to produce their own matrix and form scaffolds is a new strategy for engineering
      bladder and urethra. This self-assembly technique avoids the biosafety and
      immunological reactions related to the use of biodegradable scaffolds. Autologous
      equivalents have already been produced for pigs (bladder) and human (urethra and
      bladder). The purpose of this paper is to present a review for the existing
      methods of engineering bladder and urethra and to point toward perspectives for
      their replacement. 

PMID- 24453798
TI  - Visible and near-infrared spectroscopy analysis of a polycyclic aromatic
      hydrocarbon in soils.
AB  - Visible and near-infrared (VisNIR) spectroscopy is becoming recognised by soil
      scientists as a rapid and cost-effective measurement method for hydrocarbons in
      petroleum-contaminated soils. This study investigated the potential application
      of VisNIR spectroscopy (350-2500 nm) for the prediction of phenanthrene, a
      polycyclic aromatic hydrocarbon (PAH), in soils. A total of 150 diesel
      contaminated soil samples were used in the investigation. Partial least-squares
      (PLS) regression analysis with full cross-validation was used to develop models
      to predict the PAH compound. Results showed that the PAH compound was predicted
      well with residual prediction deviation of 2.0-2.32, root-mean-square error of
      prediction of 0.21-0.25 mg kg(-1), and coefficient of determination (r (2)) of
      0.75-0.83. The mechanism of prediction was attributed to covariation of the PAH
      with clay and soil organic carbon. Overall, the results demonstrated that the
      methodology may be used for predicting phenanthrene in soils utilizing the
      interrelationship between clay and soil organic carbon.

PMID- 24453799
TI  - 16S rRNA and omp31 gene based molecular characterization of field strains of B.
      melitensis from aborted foetus of goats in India.
AB  - Brucellosis is a reemerging infectious zoonotic disease of worldwide importance.
      In human, it is mainly caused by Brucella melitensis, a natural pathogen for
      goats. In India, a large number of goats are reared in semi-intensive to
      intensive system within the close vicinity of human being. At present, there is
      no vaccination and control strategy for caprine brucellosis in the country. Thus,
      to formulate an effective control strategy, the status of etiological agent is
      essential. To cope up with these, the present study was conducted to isolate and
      identify the prevalent Brucella species in caprine brucellosis in India. The 30
      samples (fetal membrane, fetal stomach content and vaginal swabs) collected
      throughout India from the aborted fetus of goats revealed the isolation of 05
      isolates all belonging to Brucella melitensis biovars 3. All the isolates
      produced amplification products of 1412 and 720 bp in polymerase chain reaction
      with genus and species specific 16S rRNA and omp31 gene based primers,
      respectively. Moreover, the amplification of omp31 gene in all the isolates
      confirmed the presence of immuno dominant outer membrane protein (31 kDa omp) in
      all the field isolates of B. melitensis in aborted foetus of goats in India.
      These findings can support the development of omp31 based specific serodiagnostic
      test as well as vaccine for the control of caprine brucellosis in India.

PMID- 24453800
TI  - The influence of gamma-ray irradiation on the mechanical and thermal behaviors of
      nHA/PA66 composite scaffolds.
AB  - The aim of this study is to investigate the influence of sterilization process
      using gamma -ray radiation on the melting behavior, crystallization behavior,
      thermal stability, and mechanical properties of nanohydroxyapatite/polyamide66
      (nHA/PA66) scaffolds for bone tissue engineering. The results show that the
      melting temperature, degree of crystallization, thermal stability, and mechanical
      properties of the composite scaffolds increased with the enhancement of radiation
      doses from 25 kGy to 50 kGy, especially the irradiation dose of 50 kGy which
      imposed a remarkable effect on these properties. However, a reverse trend was
      found when the 100 kGy irradiation dose was applied. In general, a conclusion can
      be drawn that sterilization using gamma -ray radiation with proper dose has no
      adverse effect on the properties of nHA/PA66 composite scaffolds.

PMID- 24453801
TI  - Development of some larval nematodes in experimental and natural animal hosts: an
      insight into development of pathological lesions vis-a-vis host-parasite
      interactions.
AB  - Infective third-stage larvae of three spiruroid nematodes, Ascarops strongylina
      and Physocephalus sexalatus of pigs and Spirocerca lupi of dogs, were recovered
      from 14 species of coprophagous beetles belonging to 4 different genera. These
      larvae were fed to rabbits and/or guinea pigs to study their development in these
      experimental hosts. Larvae of A. strongylina reached the adult stage in all
      rabbits and one guinea pig. The adult worms recovered in these hosts were 40% and
      4%, respectively, and became diminutive in comparison to their natural hosts. The
      larvae of P. sexalatus became reencysted in the gastric wall of rabbits inducing
      marked pathological changes. The infective larvae of S. lupi became
      reencapsulated in the stomach wall of the rabbit and also showed development in
      the aortic wall. Adults of Toxocara canis of dog, collected from 5 different
      regions of the Indian subcontinent, varied significantly in size. The mouse
      passage of infective larvae of one of these types led to the recovery of the
      adults from the experimental dogs that were smaller in size and caused severe
      pathology in natural experimental hosts. Developmental effects shown in
      experimental hosts and host specificity are of value in understanding the
      evolution of nematode parasitism. 

PMID- 24453802
TI  - Tolerance to cadmium of Agave lechuguilla (Agavaceae) seeds and seedlings from
      sites contaminated with heavy metals.
AB  - We investigated if seeds of Agave lechuguilla from contaminated sites with heavy
      metals were more tolerant to Cd ions than seeds from noncontaminated sites. Seeds
      from a highly contaminated site (Villa de la Paz) and from a noncontaminated site
      (Villa de Zaragoza) were evaluated. We tested the effect of Cd concentrations on
      several ecophysiological, morphological, genetical, and anatomical responses.
      Seed viability, seed germination, seedling biomass, and radicle length were
      higher for the non-polluted site than for the contaminated one. The leaves of
      seedlings from the contaminated place had more cadmium and showed peaks
      attributed to chemical functional groups such as amines, amides, carboxyl, and
      alkenes that tended to disappear due to increasing the concentration of cadmium
      than those from Villa de Zaragoza. Malformed cells in the parenchyma surrounding
      the vascular bundles were found in seedlings grown with Cd from both sites. The
      leaves from the contaminated place showed a higher metallothioneins expression in
      seedlings from the control group than that of seedlings at different Cd
      concentrations. Most of our results fitted into the hypothesis that plants from
      metal-contaminated places do not tolerate more pollution, because of the
      accumulative effect that cadmium might have on them. 

PMID- 24453804
TI  - An investigation on low velocity impact response of multilayer sandwich composite
      structures.
AB  - The effects of adding an extra layer within a sandwich panel and two different
      core types in top and bottom cores on low velocity impact loadings are studied
      experimentally in this paper. The panel includes polymer composite laminated
      sheets for faces and the internal laminated sheet called extra layer sheet, and
      two types of crushable foams are selected as the core material. Low velocity
      impact tests were carried out by drop hammer testing machine to the clamped
      multilayer sandwich panels with expanded polypropylene (EPP) and polyurethane
      rigid (PUR) in the top and bottom cores. Local displacement of the top core,
      contact force and deflection of the sandwich panel were obtained for different
      locations of the internal sheet; meanwhile the EPP and PUR were used in the top
      and bottom cores alternatively. It was found that the core material type has made
      significant role in improving the sandwich panel's behavior compared with the
      effect of extra layer location. 

PMID- 24453803
TI  - Alterations in red blood cells and plasma properties after acute single bout of
      exercise.
AB  - The aim of this study was to investigate alterations in haemoglobin conformation
      and parameters related to oxidative stress in whole erythrocytes, membranes, and
      plasma after a single bout of exercise in a group of young untrained men. Venous
      blood samples from eleven healthy young untrained males (age = 22 +/- 2 years,
      BMI = 23 +/- 2.5 kg/m(2)) were taken from the antecubital vein before an
      incremental cycling exercise test, immediately after exercise, and 1 hour after
      exercise. Individual heart rate response to this exercise was 195 +/- 12
      beats/min and the maximum wattage was 292 +/- 27 W. Immediately after exercise,
      significant increase in standard parameters (haemoglobin, haematocrit, lactate
      levels, and plasma volume) of blood was observed as well as plasma antioxidant
      capacity one hour after exercise. Reversible conformational changes in
      haemoglobin, measured using a maleimide spin label, were found immediately
      following exercise. The concentration of ascorbic acid inside erythrocytes
      significantly decreased after exercise. A significant decline in membrane thiols
      was observed one hour after exercise, but simultaneously an increase in plasma
      thiols immediately after and 1 h after exercise was also observed. This study
      shows that a single bout of exercise can lead to mobilization of defensive
      antioxidant systems in blood against oxidative stress in young untrained men.

PMID- 24453805
TI  - Antioxidant capacity as a marker for assessing the in vitro performance of the
      endangered Cistus heterophyllus.
AB  - Cistus heterophyllus subsp. carthaginensis is an endemic and endangered species
      from the SE Mediterranean coastal region of Spain. Within the framework of the
      efforts aiming to species conservation, in vitro culture techniques could be of
      interest. The aim of this study was to evaluate the antioxidant capacity of C.
      heterophyllus shoot cultures as a possible marker of in vitro performance. The
      effects of five different basal salt formulations and cytokinin levels on in
      vitro performance and antioxidant capacity were examined. K(+)/Na(+) and
      Ca(2+)/Na(+) ratios initially present in culture media greatly affected the
      antioxidant capacity (the lower the ratios the higher the antioxidant capacity).
      Increasing concentrations of BA resulted in higher antioxidant capacity. The
      results obtained point to antioxidant capacity as being a marker of incidence of
      stress conditions in in vitro cultured C. heterophyllus. A good correlation was
      found between antioxidant capacity and total soluble phenolics present in Cistus
      extracts. Catechin was identified in all the extracts and its levels were found
      to change parallel to the antioxidant capacity, pointing to a prominent role
      played by this flavonoid in C. heterophyllus defence against oxidative stress,
      which in turn affects the in vitro performance of this species. 

PMID- 24453806
TI  - Blockage of Notch signaling inhibits the migration and proliferation of retinal
      pigment epithelial cells.
AB  - The Notch signaling is an evolutionarily conserved cell-cell communication
      pathway that plays critical roles in the proliferation, survival, apoptosis, and
      fate determination of mammalian cells. Retinal pigment epithelial (RPE) cells are
      responsible for supporting the function of the neural retina and maintaining
      vision. This study investigated the function of Notch signaling in RPE cells. We
      found that the members of the Notch signaling pathway components were
      differentially expressed in RPE cells. Furthermore, blockage of Notch signaling
      inhibited the migration and proliferation of RPE cells and reduced the expression
      levels of certain Notch signaling target genes, including HES1, MYC, HEY2, and
      SOX9. Our data reveal a critical role of Notch signaling in RPE cells, suggesting
      that targeting Notch signaling may provide a novel approach for the treatment of
      ophthalmic diseases related to RPE cells. 

PMID- 24453807
TI  - Quantitative analysis and comparison of BMI among Han, Tibetan, and Uygur
      university students in Northwest China.
AB  - OBJECTIVES: To fully analyze and compare BMI among Han, Tibetan, and Uygur
      university students, to discuss the differences in their physical properties and
      physical health, and thus to provide some theoretical suggestions for the
      improvement of students' physical health. METHODS: The cross-sectional random
      cluster sampling was used to investigate 10103 Han, Tibetan, and Uygur university
      students, aged 20-24 in Northwest China, and their height and weight were
      measured to calculate BMI. The BMI classification criteria for Chinese
      established by Work Group on Obesity in China (WGOC) were used for screening.
      RESULTS: Han, Tibetan, and Uygur university students show low obesity rates but
      high overweight rates. Han, Tibetan, and Uygur university students present a high
      rate of underweight, normal weight, and overweight, respectively. Female Han
      students show higher underweight and normal weight rates, but lower overweight
      and obesity rates, than male Han students. Female Tibetan students show higher
      normal weight rate, but lower overweight and obesity rates, than male Tibetan
      students. BMI increases with age for male students but decreases with age for
      female students. Male Uygur students show higher obesity rate than female Uygur
      students. Tibetan and Uygur university students have higher BMI than other
      minorities in South China.

PMID- 24453809
TI  - Formation control of robotic swarm using bounded artificial forces.
AB  - Formation control of multirobot systems has drawn significant attention in the
      recent years. This paper presents a potential field control algorithm, navigating
      a swarm of robots into a predefined 2D shape while avoiding intermember
      collisions. The algorithm applies in both stationary and moving targets
      formation. We define the bounded artificial forces in the form of exponential
      functions, so that the behavior of the swarm drove by the forces can be adjusted
      via selecting proper control parameters. The theoretical analysis of the swarm
      behavior proves the stability and convergence properties of the algorithm. We
      further make certain modifications upon the forces to improve the robustness of
      the swarm behavior in the presence of realistic implementation considerations.
      The considerations include obstacle avoidance, local minima, and deformation of
      the shape. Finally, detailed simulation results validate the efficiency of the
      proposed algorithm, and the direction of possible futrue work is discussed in the
      conclusions. 

PMID- 24453808
TI  - A method of spatial mapping and reclassification for high-spatial-resolution
      remote sensing image classification.
AB  - This paper presents a new classification method for high-spatial-resolution
      remote sensing images based on a strategic mechanism of spatial mapping and
      reclassification. The proposed method includes four steps. First, the
      multispectral image is classified by a traditional pixel-based classification
      method (support vector machine). Second, the panchromatic image is subdivided by
      watershed segmentation. Third, the pixel-based multispectral image classification
      result is mapped to the panchromatic segmentation result based on a spatial
      mapping mechanism and the area dominant principle. During the mapping process, an
      area proportion threshold is set, and the regional property is defined as
      unclassified if the maximum area proportion does not surpass the threshold.
      Finally, unclassified regions are reclassified based on spectral information
      using the minimum distance to mean algorithm. Experimental results show that the
      classification method for high-spatial-resolution remote sensing images based on
      the spatial mapping mechanism and reclassification strategy can make use of both
      panchromatic and multispectral information, integrate the pixel- and object-based
      classification methods, and improve classification accuracy. 

PMID- 24453810
TI  - Profiling the prognosis of gastric cancer patients: is it worth correlating the
      survival with the clinical/pathological and molecular features of gastric
      cancers?
AB  - BACKGROUND: The prognosis of gastric cancer patients still remains poor. The aim
      of this study was investigating the prognostic value of several
      clinical/pathological/molecular features in a consecutive series of gastric
      cancers. METHODS: 150 R0 gastrectomies plus 77 gastric cancer patients evaluated
      for the HER2 overexpression were selected. Survival was calculated and patients
      stratified according to the stage, the T-stage, the LNRs, the LNH, and the HER2
      scoring system. ROC curves were calculated in order to compare the performance of
      the LRN and LNH systems. RESULTS: Prognosis correlated with the stage and with
      the T-stage. We documented a statistical correlation between the LNRs and the
      survival. Conversely, a LNH > 15 did not correlate with the outcomes. The ROC
      curves documented a significant performance of the LRN system, whereas a
      statistical correlation was documented for the LNH exclusively with the endpoint
      of disease-free survival. We documented a trend of worse prognosis for patients
      with an HER2 overexpression, even though it was not of statistical value.
      CONCLUSION: The LNR and the evaluation of the HER2 overexpression might be useful
      since they correlate with survival, might identify patients with a higher risk of
      recurrence, and might select patients for a tailored medical treatment.

PMID- 24453811
TI  - Analysis of mineral and heavy metal content of some commercial fruit juices by
      inductively coupled plasma mass spectrometry.
AB  - The presence of potentially toxic elements and compounds in foodstuffs is of
      intense public interest and thus requires rapid and accurate methods to determine
      the levels of these contaminants. Inductively coupled plasma mass spectrometry is
      a powerful tool for the determination of metals and nonmetals in fruit juices. In
      this study, 21 commercial fruit juices (apple, peach, apricot, orange, kiwi,
      pear, pineapple, and multifruit) present on Romanian market were investigated
      from the heavy metals and mineral content point of view by ICP-MS. Our obtained
      results were compared with those reported in literature and also with the maximum
      admissible limit in drinking water by USEPA and WHO. For Mn the obtained values
      exceeded the limits imposed by these international organizations. Co, Cu, Zn, As,
      and Cd concentrations were below the acceptable limit for drinking water for all
      samples while the concentrations of Ni and Pb exceeded the limits imposed by
      USEPA and WHO for some fruit juices. The results obtained in this study are
      comparable to those found in the literature. 

PMID- 24453813
TI  - Investigations on the antifungal effect of nerol against Aspergillus flavus
      causing food spoilage.
AB  - The antifungal efficacy of nerol (NEL) has been proved against Aspergillus flavus
      by using in vitro and in vivo tests. The mycelial growth of A. flavus was
      completely inhibited at concentrations of 0.8 MU L/mL and 0.1 MU L/mL NEL in the
      air at contact and vapor conditions, respectively. The NEL also had an evident
      inhibitory effect on spore germination in A. flavus along with NEL concentration
      as well as time-dependent kinetic inhibition. The NEL presented noticeable
      inhibition on dry mycelium weight and synthesis of aflatoxin B1 (AFB1) by A.
      flavus, totally restraining AFB1 production at 0.6 MU L/mL. In real food system,
      the efficacy of the NEL on resistance to decay development in cherry tomatoes was
      investigated in vivo by exposing inoculated and control fruit groups to NEL vapor
      at different concentration. NEL vapors at 0.1 MU L/mL air concentration
      significantly reduced artificially contaminated A. flavus and a broad spectrum of
      fungal microbiota. Results obtained from presented study showed that the NEL had
      a great antifungal activity and could be considered as a benefit and safe tool to
      control food spoilage.

PMID- 24453812
TI  - Five Pistacia species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P.
      lentiscus): a review of their traditional uses, phytochemistry, and pharmacology.
AB  - Pistacia, a genus of flowering plants from the family Anacardiaceae, contains
      about twenty species, among them five are more popular including P. vera, P.
      atlantica, P. terebinthus, P. khinjuk, and P. lentiscus. Different parts of these
      species have been used in traditional medicine for various purposes like tonic,
      aphrodisiac, antiseptic, antihypertensive and management of dental,
      gastrointestinal, liver, urinary tract, and respiratory tract disorders.
      Scientific findings also revealed the wide pharmacological activities from
      various parts of these species, such as antioxidant, antimicrobial, antiviral,
      anticholinesterase, anti-inflammatory, antinociceptive, antidiabetic, antitumor,
      antihyperlipidemic, antiatherosclerotic, and hepatoprotective activities and also
      their beneficial effects in gastrointestinal disorders. Various types of
      phytochemical constituents like terpenoids, phenolic compounds, fatty acids, and
      sterols have also been isolated and identified from different parts of Pistacia
      species. The present review summarizes comprehensive information concerning
      ethnomedicinal uses, phytochemistry, and pharmacological activities of the five
      mentioned Pistacia species. 

PMID- 24453814
TI  - Spatiotemporal variation and risk assessment of pesticides in water of the lower
      catchment basin of Acheloos River, Western Greece.
AB  - A three-year monitoring survey (March 2005-February 2008) was conducted to
      investigate, on monthly basis, the presence of thirty pesticides belonging to
      various categories and metabolites, in Acheloos River (Western Greece), one of
      the most important water resources in Greece. Six sampling stations along the
      river were established. Water analyses were performed using solid-phase
      extraction combined with gas chromatography with flame thermionic detector and
      mass spectrometry. Statistical analysis using one-way ANOVA and Duncan's multiple
      range test (P < 0.05) was used to compare annual mean concentrations of
      pesticides, seasonal and spatial distribution. In general, the highest mean
      concentrations of the pesticides were recorded at the three stations downstream.
      The greatest average concentrations were determined during spring and summer in
      agreement with the pesticide application period. The observed lower
      concentrations after 2006 reflect the land-use change because of the elimination
      of tobacco, the main cultivation of the area for many decades. The compounds most
      frequently detected were diazinon (78.6%), DEA (69.3%), and fenthion (52.6%).
      Environmental risk assessment using risk quotient (RQ) approach showed high risk
      for six insecticides in 2005 and one in 2007. A compliance with the European
      Environmental Quality Standards (EQS) was observed for the priority pesticides. 

PMID- 24453815
TI  - A universal fast algorithm for sensitivity-based structural damage detection.
AB  - Structural damage detection using measured response data has emerged as a new
      research area in civil, mechanical, and aerospace engineering communities in
      recent years. In this paper, a universal fast algorithm is presented for
      sensitivity-based structural damage detection, which can quickly improve the
      calculation accuracy of the existing sensitivity-based technique without any high
      order sensitivity analysis or multi-iterations. The key formula of the universal
      fast algorithm is derived from the stiffness and flexibility matrix spectral
      decomposition theory. With the introduction of the key formula, the proposed
      method is able to quickly achieve more accurate results than that obtained by the
      original sensitivity-based methods, regardless of whether the damage is small or
      large. Three examples are used to demonstrate the feasibility and superiority of
      the proposed method. It has been shown that the universal fast algorithm is
      simple to implement and quickly gains higher accuracy over the existing
      sensitivity-based damage detection methods. 

PMID- 24453816
TI  - The oscillation on solutions of some classes of linear differential equations
      with meromorphic coefficients of finite [p, q]-order.
AB  - This paper considers the oscillation on meromorphic solutions of the second-order
      linear differential equations with the form f'' + A(z)f = 0, where A(z) is a
      meromorphic function with [p, q]-order. We obtain some theorems which are the
      improvement and generalization of the results given by Bank and Laine, Cao and
      Li, Kinnunen, and others. 

PMID- 24453817
TI  - Neoplastic meningitis: How MRI and CSF cytology are influenced by CSF cell count
      and tumor type.
AB  - BACKGROUND: Although CSF cytology and MRI are standard methods to diagnose
      neoplastic meningitis (NM), this complication of neoplastic disease remains
      difficult to detect. We therefore reevaluated the sensitivity of gadolinium (GD)
      enhanced MRI and cerebrospinal-fluid (CSF)-cytology and the relevance of tumor
      type and CSF cell count. METHODS: We retrospectively identified 111 cases of NM
      diagnosed in our CSF laboratory since 1990 with complete documentation of both
      MRI and CSF cytology. 37 had haematological and 74 solid neoplasms. CSF cell
      counts were increased in 74 and normal in 37 patients. RESULTS: In hematological
      neoplasms, MRI was positive in 49% and CSF cytology in 97%. In solid tumors, the
      sensitivity of MRI was 80% and of cytology 78%. With normal CSF cell counts, MRI
      was positive in 59% (50% hematological, 72% solid malignancies) and CSF cytology
      in 76% (92% in hematological, 68% in solid neoplasms). In cases of elevated cell
      counts, the sensitivity of MRI was 72% (50% for hematological, 83% for solid
      malignancies) and of CSF cytology 91% (100% for haematological and 85% for solid
      neoplasms). 91% of cytologically positive cases were diagnosed at first and
      another 7% at second lumbar puncture. Routine protein analyses had a low
      sensitivity in detecting NM. CONCLUSIONS: The high overall sensitivity of MRI was
      only confirmed for NM from solid tumors and for elevated CSF cell counts. With
      normal cell counts and haematological neoplasms, CSF-cytology was superior to
      MRI. None of the analysed routine CSF proteins had an acceptable sensitivity and
      specificity in detecting leptomeningeal disease.

PMID- 24453818
TI  - Structure and microhardness of cu-ta joints produced by explosive welding.
AB  - The structure and microhardness of Cu-Ta joints produced by explosive welding
      were studied. It was found that, during explosive welding, an intermediate layer
      20?40  MU m thick with a finely dispersed heterophase structure, formed between
      the welded copper and tantalum plates. The structure of the layer was studied by
      scanning and transmission electron microscopy. Microvolumes with tantalum
      particles distributed in a copper matrix and microvolumes of copper particles in
      a tantalum matrix were detected. The tantalum particles in copper have a size of
      5?500 nm, with a predominance of 5?50 nm particles. A mechanism for the formation
      of the finely dispersed heterophase structure in explosive welding is proposed.
      The microhardness of interlayers with the heterophase structure reaches 280 HV,
      which far exceeds the microhardness of copper (~130 HV) and tantalum (~160 HV).
      Many twins of deformation origin were found in the structure of the copper plate.
      The effect of heating temperature in the range from 100 to 900 degrees C on the
      microhardness of copper, tantalum, and the Cu-Ta welded joint was studied. Upon
      heating to 900 degrees C, the microhardness of the intermediate layer decreases
      from 280 to 150 HV. The reduction in the strength properties of the weld material
      is mainly due to structural transformations in copper.

PMID- 24453819
TI  - Satellite observations of NO2 trend over Romania.
AB  - Satellite-based measurements of atmospheric trace gases loading give a realistic
      image of atmospheric pollution at global, regional, and urban level. The aim of
      this paper is to investigate the trend of atmospheric NO2 content over Romania
      for the period 1996-2010 for several regions which are generally characterized by
      different pollutant loadings, resulting from GOME-1, SCIAMACHY, OMI, and GOME-2
      instruments. Satellite results are then compared with ground-based in situ
      measurements made in industrial and relatively clean areas of one major city in
      Romania. This twofold approach will help in estimating whether the trend of NO2
      obtained by means of data satellite retrievals can be connected with the
      evolution of national industry and transportation. 

PMID- 24453821
TI  - Mathematical identification of influential parameters on the elastic buckling of
      variable geometry plate.
AB  - The problem of elastic stability of plates with square, rectangular, and circular
      holes as well as slotted holes was discussed. The existence of the hole reduces
      the deformation energy of the plate and it affects the redistribution of stress
      flow in comparison to a uniform plate which causes a change of the external
      operation of compressive forces. The distribution of compressive force is defined
      as the approximate model of plane state of stress. The significant parameters of
      elastic stability compared to the uniform plate, including the dominant role of
      the shape, size, and orientation of the hole were identified. Comparative
      analysis of the shape of the hole was carried out on the data from the
      literature, which are based on different approaches and methods. Qualitative and
      quantitative accordance of the results has been found out and it verifies exposed
      methodology as applicable in the study of the phenomenon of elastic stability.
      Sensitivity factor is defined that is proportional to the reciprocal value of the
      buckling coefficient and it is a measure of sensitivity of plate to the existence
      of the hole. Mechanism of loss of stability is interpreted through the absorption
      of the external operation, induced by the shape of the hole. 

PMID- 24453820
TI  - Serum N-glycan profiling predicts prognosis in patients undergoing hemodialysis.
AB  - BACKGROUND: The aim of this study is to evaluate the usefulness of serum N-glycan
      profiling for prognosis in hemodialysis patients. METHODS: Serum N-glycan
      analysis was performed in 100 hemodialysis patients in June 2008 using the
      glycoblotting method, which allows high-throughput, comprehensive, and
      quantitative N-glycan analysis. All patients were longitudinally followed up for
      5 years. To evaluate the independent predictors for prognosis, patients'
      background, blood biochemistry, and N-glycans intensity were analyzed using Cox
      regression multivariate analysis. Selected N-glycans and independent factors were
      evaluated using the log-rank test with the Kaplan-Meier method to identify the
      predictive indicators for prognosis. Each patient was categorized according to
      the number of risk factors to evaluate the predictive potential of the risk
      criteria for prognosis. RESULTS: In total, 56 N-glycan types were identified in
      the hemodialysis patients. Cox regression multivariate analysis showed
      cardiovascular events, body mass index, maximum intima media thickness, and the
      serum N-glycan intensity of peak number 49 were predictive indicators for overall
      survival. Risk classification according to the number of independent risk factors
      revealed significantly poor survival by increasing the number of risk factors.
      CONCLUSIONS: Serum N-glycan profiling may have a potential to predict prognosis
      in patients undergoing hemodialysis.

PMID- 24453822
TI  - An effective hybrid self-adapting differential evolution algorithm for the joint
      replenishment and location-inventory problem in a three-level supply chain.
AB  - The integration with different decisions in the supply chain is a trend, since it
      can avoid the suboptimal decisions. In this paper, we provide an effective
      intelligent algorithm for a modified joint replenishment and location-inventory
      problem (JR-LIP). The problem of the JR-LIP is to determine the reasonable number
      and location of distribution centers (DCs), the assignment policy of customers,
      and the replenishment policy of DCs such that the overall cost is minimized.
      However, due to the JR-LIP's difficult mathematical properties, simple and
      effective solutions for this NP-hard problem have eluded researchers. To find an
      effective approach for the JR-LIP, a hybrid self-adapting differential evolution
      algorithm (HSDE) is designed. To verify the effectiveness of the HSDE, two
      intelligent algorithms that have been proven to be effective algorithms for the
      similar problems named genetic algorithm (GA) and hybrid DE (HDE) are chosen to
      compare with it. Comparative results of benchmark functions and randomly
      generated JR-LIPs show that HSDE outperforms GA and HDE. Moreover, a sensitive
      analysis of cost parameters reveals the useful managerial insight. All
      comparative results show that HSDE is more stable and robust in handling this
      complex problem especially for the large-scale problem. 

PMID- 24453823
TI  - A systematic method of interconnection optimization for dense-array concentrator
      photovoltaic system.
AB  - This paper presents a new systematic approach to analyze all possible array
      configurations in order to determine the most optimal dense-array configuration
      for concentrator photovoltaic (CPV) systems. The proposed method is fast, simple,
      reasonably accurate, and very useful as a preliminary study before constructing a
      dense-array CPV panel. Using measured flux distribution data, each CPV cells'
      voltage and current values at three critical points which are at short-circuit,
      open-circuit, and maximum power point are determined. From there, an algorithm
      groups the cells into basic modules. The next step is I-V curve prediction, to
      find the maximum output power of each array configuration. As a case study,
      twenty different I-V predictions are made for a prototype of nonimaging planar
      concentrator, and the array configuration that yields the highest output power is
      determined. The result is then verified by assembling and testing of an actual
      dense-array on the prototype. It was found that the I-V curve closely resembles
      simulated I-V prediction, and measured maximum output power varies by only 1.34%.

PMID- 24453824
TI  - High genetic diversity and insignificant interspecific differentiation in
      Opisthopappus Shih, an endangered cliff genus endemic to the Taihang Mountains of
      China.
AB  - Opisthopappus Shih is endemic to the Taihang Mountains, China. It grows in the
      crevice of cliffs and is in fragmented distribution. This genus consists of two
      species, namely, O. taihangensis (Ling) Shih and O. longilobus Shih, which are
      both endangered plants in China. This study adopted intersimple sequence repeat
      markers (ISSR) to analyze the genetic diversity and genetic structure from
      different levels (genus, species, and population) in this genus. A total of 253
      loci were obtained from 27 primers, 230 of which were polymorphic loci with a
      proportion of polymorphic bands (PPB) of up to 90.91% at genus level. At species
      level, both O. taihangensis (PPB = 90.12%, H = 0.1842, and I = 0.289) and O.
      longilobus (PPB = 95.21%, H = 0.2226, and I = 0.3542) have high genetic
      diversity. Their respective genetic variation mostly existed within the
      population. And genetic variation in O. longilobus (84.95%) was higher than that
      in O. taihangensis (80.45%). A certain genetic differentiation among populations
      in O. taihangensis was found (G(st) = 0.2740, Phi(st) = 0.196) and genetic
      differentiation in O. longilobus was very small (G(st) = 0.1034, Phi(st) =
      0.151). Gene flow in different degrees (N(m) = 1.325 and 4.336, resp.) and mating
      system can form the existing genetic structures of these two species.
      Furthermore, genetic differentiation coefficient (G(st) = 0.0453) between species
      and the clustering result based on the genetic distance showed that interspecific
      differentiation between O. taihangensis and O. longilobus was not significant and
      could occur lately.

PMID- 24453825
TI  - The damage capacity of Mahanarva spectabilis (Distant, 1909) (Hemiptera:
      Cercopidae) adults on Brachiaria ruziziensis pasture.
AB  - The aim of this study was to determine the damage caused by adult Mahanarva
      spectabilis (Distant, 1909) (Hemiptera: Cercopidae) on Brachiaria ruziziensis
      (Germain & Evard) under field conditions. A total of 0, 4, 8, 12, or 16 M.
      spectabilis adults per plot were maintained for 6 days. Thereafter, the insects
      were removed from the plant, and the following parameters were evaluated:
      chlorophyll content, damage score, dry as well as fresh weights, percentage of
      shoots' dry matter, and the forage's ability to regrow. The chlorophyll content
      was significantly reduced; the damage score and percentage of dry matter in
      plants increased depending on the increased insect infestation density after 6
      days of exposure. In contrast, no change was observed on the B. ruziziensis fresh
      and dry weights as well as the regrowth capacity depending on the M. spectabilis
      infestation densities. Attacks by 8 adult M. spectabilis per clump of B.
      ruziziensis with an average of 80 tillers for 6 days were sufficient to reduce
      the chlorophyll content and the functional plant loss index. This density can be
      a reference for spittlebug integrated management in Brachiaria. 

PMID- 24453826
TI  - A source-initiated on-demand routing algorithm based on the Thorup-Zwick theory
      for mobile wireless sensor networks.
AB  - The unreliability and dynamics of mobile wireless sensor networks make it hard to
      perform end-to-end communications. This paper presents a novel source-initiated
      on-demand routing mechanism for efficient data transmission in mobile wireless
      sensor networks. It explores the Thorup-Zwick theory to achieve source-initiated
      on-demand routing with time efficiency. It is able to find out shortest routing
      path between source and target in a network and transfer data in linear time. The
      algorithm is easy to be implemented and performed in resource-constrained mobile
      wireless sensor networks. We also evaluate the approach by analyzing its cost in
      detail. It can be seen that the approach is efficient to support data
      transmission in mobile wireless sensor networks. 

PMID- 24453827
TI  - Cubical sets and trace monoid actions.
AB  - This paper is devoted to connections between trace monoids and cubical sets. We
      prove that the category of trace monoids is isomorphic to the category of
      generalized tori and it is a reflective subcategory of the category of cubical
      sets. Adjoint functors between the categories of cubical sets and trace monoid
      actions are constructed. These functors carry independence preserving morphisms
      in the independence preserving morphisms. This allows us to build adjoint
      functors between the category of weak asynchronous systems and the category of
      higher dimensional automata. 

PMID- 24453828
TI  - Scientific validation of the medicinal efficacy of Tinospora cordifolia.
AB  - Present communication reports the scientific evaluation of Tinospora cordifolia
      for its medicinal efficacy which includes phytochemical screening, antimicrobial,
      antioxidant, and anticancer activities of the plant. Secondary metabolites
      including anthraquinones, terpenoids, and saponins were present in many extracts
      in addition to phenolics. Total phenol contents in various extracts were found in
      the range of 8.75-52.50 catechol equivalent per gram (CE/g). In disc diffusion
      assays, polar extracts exhibited considerable inhibition against Klebsiella
      pneumoniae. Several other extracts also showed antibacterial activity against
      pathogenic strains of E. coli, Pseudomonas spp., and Proteus spp. Minimum
      bactericidal concentration (MBC) values of potential extracts were found between
      1.29 and 22.73 mg/mL. The lowest MBC (1.29 mg/mL) was recorded for acetone and
      ethyl acetate extracts against K. pneumoniae and Pseudomonas spp., respectively.
      The antioxidant activity of the extracts was comparable to that of standard
      antioxidants and concentration-dependent response was shown in reducing power
      assay. Aqueous extracts demonstrated substantial metal ion chelating activity (67
      95%) at lower concentrations (10-40 MU g/mL). Other extracts also exhibited
      considerable metal chelating response. Most of the extracts revealed considerable
      inhibition of MCF-7 cancer cell line. The study established remarkable
      antibacterial, antioxidant, and anticancer potential in T. cordifolia stem
      extracts.

PMID- 24453829
TI  - Heat dissipation for microprocessor using multiwalled carbon nanotubes based
      liquid.
AB  - Carbon nanotubes (CNTs) are one of the most valuable materials with high thermal
      conductivity (2000 W/m . K compared with thermal conductivity of Ag 419 W/m . K).
      This suggested an approach in applying the CNTs in thermal dissipation system for
      high power electronic devices, such as computer processor and high brightness
      light emitting diode (HB-LED). In this work, multiwalled carbon nanotubes
      (MWCNTs) based liquid was made by COOH functionalized MWCNTs dispersed in
      distilled water with concentration in the range between 0.2 and 1.2 gram/liter.
      MWCNT based liquid was used in liquid cooling system to enhance thermal
      dissipation for computer processor. By using distilled water in liquid cooling
      system, CPU's temperature decreases by about 10 degrees C compared with using fan
      cooling system. By using MWCNT liquid with concentration of 1 gram/liter MWCNTs,
      the CPU's temperature decreases by 7 degrees C compared with using distilled
      water in cooling system. Theoretically, we also showed that the presence of
      MWCNTs reduced thermal resistance and increased the thermal conductivity of
      liquid cooling system. The results have confirmed the advantages of the MWCNTs
      for thermal dissipation systems for the MU -processor and other high power
      electronic devices. 

PMID- 24453830
TI  - Microstructure and mechanical properties of recycled aggregate concrete in
      seawater environment.
AB  - This study aims to conduct research about the microstructure and basic properties
      of recycled aggregate concrete under seawater corrosion. Concrete specimens were
      fabricated and tested with different replacement percentages of 0%, 30%, and 60%
      after immersing in seawater for 4, 8, 12, and 16 months, respectively. The basic
      properties of recycled aggregate concrete (RAC) including the compressive
      strength, the elastic modulus, and chloride penetration depth were explicitly
      investigated. And the microstructure of recycled concrete aggregate (RCA) was
      revealed to find the seawater corrosion by using scanning electron microscope
      (SEM). The results showed that higher amount of the RCA means more porosity and
      less strength, which could lower both the compressive strength and resistance to
      chloride penetration. This research could be a guide in theoretical and numerical
      analysis for the design of RAC structures. 

PMID- 24453832
TI  - Coordinating a supply chain with price and advertisement dependent stochastic
      demand.
AB  - This paper investigates pricing and ordering as well as advertising coordination
      issues in a single-manufacturer single-retailer supply chain, where the
      manufacturer sells a newsvendor-type product through the retailer who faces a
      stochastic demand depending on both retail price and advertising expenditure.
      Under the assumption that the market demand has a multiplicative functional form,
      the Stackelberg and cooperative game models are developed, and the closed form
      solution to each model is provided as well. Comparisons and insights are
      presented. We show that a properly designed revenue-cost-sharing contract can
      achieve supply chain coordination and lead to a Pareto improving win-win
      situation for channel members. We also discuss the allocation of the extra joint
      profit according to individual supply chain members' risk preferences and
      negotiating powers. 

PMID- 24453831
TI  - Von Willebrand factor antigen predicts response to double dose of aspirin and
      clopidogrel by PFA-100 in patients undergoing primary angioplasty for ST
      elevation myocardial infarction.
AB  - Von Willebrand factor (VWF) is an emerging risk factor in acute coronary
      syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI)
      is sensitive to functional alterations of VWF and also identifies patients with
      high on-treatment platelet reactivity (HPR). The objective of this study was to
      verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected
      by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS
      13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation
      myocardial infarction undergoing primary PCI with HPR at day 5 after PCI.
      Patients recruited were then randomized between a standard dose (SD, n = 58) or
      DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up.
      Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13
      analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1
      and 2 we observed a significantly higher CEPI closure times (CT) in DD as
      compared to SD (P < 0.001). Delta of CEPI-CT (T1 - T0) was significantly related
      to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a
      significantly higher level of VWF at T0. Finally, in a multivariate model
      analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT
      response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is
      reversible by DD of aspirin and clopidogrel; the response is predicted by basal
      levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification
      in acute coronary syndromes given its sensitivity to VWF. 

PMID- 24453833
TI  - Study of montmorillonite clay for the removal of copper (II) by adsorption: full
      factorial design approach and cascade forward neural network.
AB  - An intensive study has been made of the removal efficiency of Cu(II) from
      industrial leachate by biosorption of montmorillonite. A 2(4) factorial design
      and cascade forward neural network (CFNN) were used to display the significant
      levels of the analyzed factors on the removal efficiency. The obtained model
      based on 2(4) factorial design was statistically tested using the well-known
      methods. The statistical analysis proves that the main effects of analyzed
      parameters were significant by an obtained linear model within a 95% confidence
      interval. The proposed CFNN model requires less experimental data and minimum
      calculations. Moreover, it is found to be cost-effective due to inherent
      advantages of its network structure. Optimization of the levels of the analyzed
      factors was achieved by minimizing adsorbent dosage and contact time, which were
      costly, and maximizing Cu(II) removal efficiency. The suggested optimum
      conditions are initial pH at 6, adsorbent dosage at 10 mg/L, and contact time at
      10 min using raw montmorillonite with the Cu(II) removal of 80.7%. At the optimum
      values, removal efficiency was increased to 88.91% if the modified
      montmorillonite was used.

PMID- 24453834
TI  - Computationally inexpensive approach for pitch control of offshore wind turbine
      on barge floating platform.
AB  - Offshore floating wind turbine (OFWT) has gained increasing attention during the
      past decade because of the offshore high-quality wind power and complex load
      environment. The control system is a tradeoff between power tracking and fatigue
      load reduction in the above-rated wind speed area. In allusion to the external
      disturbances and uncertain system parameters of OFWT due to the proximity to load
      centers and strong wave coupling, this paper proposes a computationally
      inexpensive robust adaptive control approach with memory-based compensation for
      blade pitch control. The method is tested and compared with a baseline controller
      and a conventional individual blade pitch controller with the "NREL offshore 5 MW
      baseline wind turbine" being mounted on a barge platform run on FAST and
      Matlab/Simulink, operating in the above-rated condition. It is shown that the
      advanced control approach is not only robust to complex wind and wave
      disturbances but adaptive to varying and uncertain system parameters as well. The
      simulation results demonstrate that the proposed method performs better in
      reducing power fluctuations, fatigue loads and platform vibration as compared to
      the conventional individual blade pitch control.

PMID- 24453835
TI  - Determination of ivermectin in medicated feeds by liquid chromatography with
      fluorescence detection.
AB  - A labour- and time-effective analytical procedure for determination of ivermectin
      in medicated feed at recommended level of 2.0 mg kg(-1) has been developed and
      validated. The analyte was extracted from grinded feed samples with acetonitrile
      and derivatisated with N-methylimidazole and trifluoracetic anhydride. The
      fluorescent derivatives were analysed by liquid chromatography method using C8
      column. The isocratic conditions using acetonitrile, methanol, water, and
      tetrahydrofuran were applied. Fluorescence detection was performed at 365 nm
      (excitation) and 475 nm (emission) wavelengths. The total analysis time was 10
      min. The validation results of the method (within-laboratory reproducibility 4.0%
      CV, mean recovery 100.1%) confirm the appropriate precision and accuracy of the
      developed method.

PMID- 24453836
TI  - Optimization of green synthesis of silver nanoparticles from leaf extracts of
      Pimenta dioica (Allspice).
AB  - Production of silver nanoparticles from the leaf extracts of Pimenta dioica is
      reported for the first time in this paper. Three different sets of leaves were
      utilized for the synthesis of nanoparticles-fresh, hot-air oven dried, and sun
      dried. These nanoparticles were characterized using UV-Vis spectroscopy and AFM.
      The results were diverse in that different sizes were seen for different leaf
      conditions. Nanoparticles synthesized using sun-dried leaves (produced using a
      particular ratio (1 : 0.5) of the leaf extract sample and silver nitrate (1 mM),
      resp.) possessed the smallest sizes. We believe that further optimization of the
      current green-synthesis method would help in the production of monodispersed
      silver nanoparticles having great potential in treating several diseases.

PMID- 24453837
TI  - The impacts of different expansion modes on performance of small solar energy
      firms: perspectives of absorptive capacity.
AB  - The characteristics of firm's expansion by differentiated products and
      diversified products are quite different. However, the study employing absorptive
      capacity to examine the impacts of different modes of expansion on performance of
      small solar energy firms has never been discussed before. Then, a conceptual
      model to analyze the tension between strategies and corporate performance is
      proposed to filling the vacancy. After practical investigation, the results show
      that stronger organizational institutions help small solar energy firms expanded
      by differentiated products increase consistency between strategies and corporate
      performance; oppositely, stronger working attitudes with weak management controls
      help small solar energy firms expanded by diversified products reduce variance
      between strategies and corporate performance. 

PMID- 24453838
TI  - Molecular and virological investigation of a focal chikungunya outbreak in
      northern India.
AB  - Chikungunya (CHIK) fever is one of the most important arboviral infections of
      medical significance. The objective of the present study is to identify and
      characterize the etiology of a focal febrile arthritis outbreak from Gwalior,
      northern India, during October-November 2010. A detailed virological (isolation)
      and molecular (end-point RT-PCR, quantitative RT-PCR, and nucleotide sequencing)
      investigation of this outbreak was carried out by collecting and studying 52
      clinical samples and 15 mosquito pools from the affected region. The
      investigation revealed the presence of CHIK viral RNA in 29% of clinical samples
      and 13% mosquito pool by RT-PCR. The quantification of CHIK viral RNA in samples
      varied from 10(2.50) to 10(6.67) copies/mL, as demonstrated through quantitative
      RT-PCR. In addition, six CHIK viruses were isolated from RT-PCR positive samples.
      The nucleotide sequences of partial E1 gene of five representative CHIK viruses
      were deciphered, which revealed that all the viral strains from this outbreak
      belong to the recently emerging ECS African genotype. Identification of
      Chikungunya virus ECSA African genotype as the etiology of the present outbreak
      confirms the continued circulation of the novel genotype, since 2006, in India.
      The identification of CHIK virus in Aedes aegypti also confirmed it as the major
      vector in northern India. 

PMID- 24453839
TI  - Gender differences in maladaptive cognitive schema in orphans in Dakahlia, Egypt.
AB  - The objective of this study was to assess the gender differences of maladaptive
      cognitive schema among orphans in Dakahlia governorate orphanages. A cross
      sectional comparative study included 152 orphan boys and 48 orphan girls in all
      orphanages homes in Dakahlia governorate, Egypt. Data collection tools included a
      structured interview questionnaire for personal data; early maladaptive schema
      questionnaire-short form (EMSQ-SF). The mean score of the total YSQ and all the
      subscales, except self-sacrifice and unrelenting standards, are significantly
      higher among females than males. Attention should be given to the psychological
      care of the orphans especially security, trust, confidence, and autonomy with
      more attention to orphan girls. 

PMID- 24453841
TI  - A multipopulation PSO based memetic algorithm for permutation flow shop
      scheduling.
AB  - The permutation flow shop scheduling problem (PFSSP) is part of production
      scheduling, which belongs to the hardest combinatorial optimization problem. In
      this paper, a multipopulation particle swarm optimization (PSO) based memetic
      algorithm (MPSOMA) is proposed in this paper. In the proposed algorithm, the
      whole particle swarm population is divided into three subpopulations in which
      each particle evolves itself by the standard PSO and then updates each
      subpopulation by using different local search schemes such as variable
      neighborhood search (VNS) and individual improvement scheme (IIS). Then, the best
      particle of each subpopulation is selected to construct a probabilistic model by
      using estimation of distribution algorithm (EDA) and three particles are sampled
      from the probabilistic model to update the worst individual in each
      subpopulation. The best particle in the entire particle swarm is used to update
      the global optimal solution. The proposed MPSOMA is compared with two recently
      proposed algorithms, namely, PSO based memetic algorithm (PSOMA) and hybrid
      particle swarm optimization with estimation of distribution algorithm (PSOEDA),
      on 29 well-known PFFSPs taken from OR-library, and the experimental results show
      that it is an effective approach for the PFFSP. 

PMID- 24453840
TI  - Chronologic versus biologic aging of the human choroid.
AB  - Several aspects of chronologic and biologic aging in the human choroid are
      reviewed from the literature. They often reveal methodological problems for age
      dependent changes of the following parameters: choroidal thickness, choroidal
      pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On
      reinterpreting some data of studies concerning Bruch's membrane, changes observed
      at different age points seem more likely to be nonlinear. Concluding from the
      data presented so far, chronologic aging should not be used as a factor for
      physiological changes in the human choroid. Longitudinal study designs are
      necessary to further establish the impact of age. Meanwhile, a more biologic
      oriented model of aging processes in the choroid should be established, including
      specified conditions (e.g., light exposure and refractory state). This would help
      to define more individual strategies for prevention and early stages of a certain
      defined disease. 

PMID- 24453842
TI  - Effect of Lactobacillus plantarum C014 on innate immune response and disease
      resistance against Aeromonas hydrophila in hybrid catfish.
AB  - A bacterial strain isolated from intestines of hybrid catfish (Clarias gariepinus
      Male * Clarias macrocephalus Female) exhibited an in vitro inhibitory effect on a
      fish pathogen, Aeromonas hydrophila TISTR 1321. By using the 16S rDNA sequence
      analysis, it was identified as Lactobacillus plantarum C014. To examine whether
      L. plantarum C014 had potential for use as an immunostimulant and biocontrol
      agent in hybrid catfish, the fish diet supplemented with L. plantarum C014 (10(7)
      CFU/g diet) was prepared and used for the in vivo investigation of its effect on
      innate immune response and disease resistance of hybrid catfish. Two innate
      immune response parameters, phagocytic activity of blood leukocytes and plasma
      lysozyme activity, were significantly enhanced in the treated fish after 45 days
      of feeding. Feeding the fish with the L. plantarum C014 supplemented diet for 45
      days before challenging them with A. hydrophila at the dose of LD50 could reduce
      the mortality rate of the fish from 50% (in control group) to 0% (in treated
      group). Based on its origin and beneficial effect on innate immune response and
      disease resistance, L. plantarum C014 may be a potential candidate for use as a
      natural and safe immunostimulant and biocontrol agent in hybrid catfish.

PMID- 24453843
TI  - Expression and characterization of Coprothermobacter proteolyticus alkaline
      serine protease.
AB  - A putative protease gene (aprE) from the thermophilic bacterium Coprothermobacter
      proteolyticus was cloned and expressed in Bacillus subtilis. The enzyme was
      determined to be a serine protease based on inhibition by PMSF. Biochemical
      characterization demonstrated that the enzyme had optimal activity under alkaline
      conditions (pH 8-10). In addition, the enzyme had an elevated optimum temperature
      (60 degrees C). The protease was also stable in the presence of many surfactants
      and oxidant. Thus, the C. proteolyticus protease has potential applications in
      industries such as the detergent market. 

PMID- 24453844
TI  - Raised serum adenosine deaminase level in nonobese type 2 diabetes mellitus.
AB  - The role of inflammation being minimal in the pathogenesis of type 2 diabetes
      mellitus (T2DM) in nonobese patients; the aim of the study was to investigate the
      role of adenosine deaminase (ADA) and see its association with diabetes mellitus.
      The preliminary case control study comprised of 56 cases and 45 healthy controls
      which were age and sex matched. 3 mL venous blood samples were obtained from the
      patients as well as controls after 8-10 hours of fasting. Serum ADA and routine
      biochemical parameters were analyzed. Serum ADA level was found significantly
      higher among nonobese T2DM subjects with respect to controls (38.77 +/- 14.29
      versus 17.02 +/- 5.74 U/L; P < 0.0001). Serum ADA level showed a significant
      positive correlation with fasting plasma glucose (r = 0.657; P < 0.0001) level
      among nonobese T2DM subjects, but no significant correlation was observed in
      controls (r = -0.203; P = 0.180). However, no correlation was observed between
      serum ADA level compared to BMI and HbA1c levels. Our study shows higher serum
      ADA, triglycerides (TG) and fasting plasma glucose (FPG) levels in nonobese T2DM
      patients, and a strong correlation between ADA and FPG which suggests an
      association between ADA and nonobese T2DM subjects.

PMID- 24453845
TI  - Influence of disturbance on soil respiration in biologically crusted soil during
      the dry season.
AB  - Soil respiration (Rs) is a major pathway for carbon cycling and is a complex
      process involving abiotic and biotic factors. Biological soil crusts (BSCs) are a
      key biotic component of desert ecosystems worldwide. In desert ecosystems, soils
      are protected from surface disturbance by BSCs, but it is unknown whether Rs is
      affected by disturbance of this crust layer. We measured Rs in three types of
      disturbed and undisturbed crusted soils (algae, lichen, and moss), as well as
      bare land from April to August, 2010, in Mu Us desert, northwest China. Rs was
      similar among undisturbed soils but increased significantly in disturbed moss and
      algae crusted soils. The variation of Rs in undisturbed and disturbed soil was
      related to soil bulk density. Disturbance also led to changes in soil organic
      carbon and fine particles contents, including declines of 60-70% in surface soil
      C and N, relative to predisturbance values. Once BSCs were disturbed, Q 10
      increased. Our findings indicate that a loss of BSCs cover will lead to greater
      soil C loss through respiration. Given these results, understanding the
      disturbance sensitivity impact on Rs could be helpful to modify soil management
      practices which promote carbon sequestration. 

PMID- 24453846
TI  - Determination of important topographic factors for landslide mapping analysis
      using MLP network.
AB  - Landslide is one of the natural disasters that occur in Malaysia. Topographic
      factors such as elevation, slope angle, slope aspect, general curvature, plan
      curvature, and profile curvature are considered as the main causes of landslides.
      In order to determine the dominant topographic factors in landslide mapping
      analysis, a study was conducted and presented in this paper. There are three main
      stages involved in this study. The first stage is the extraction of extra
      topographic factors. Previous landslide studies had identified mainly six
      topographic factors. Seven new additional factors have been proposed in this
      study. They are longitude curvature, tangential curvature, cross section
      curvature, surface area, diagonal line length, surface roughness, and rugosity.
      The second stage is the specification of the weight of each factor using two
      methods. The methods are multilayer perceptron (MLP) network classification
      accuracy and Zhou's algorithm. At the third stage, the factors with higher
      weights were used to improve the MLP performance. Out of the thirteen factors,
      eight factors were considered as important factors, which are surface area,
      longitude curvature, diagonal length, slope angle, elevation, slope aspect,
      rugosity, and profile curvature. The classification accuracy of multilayer
      perceptron neural network has increased by 3% after the elimination of five less
      important factors. 

PMID- 24453847
TI  - Pharmaceutical point of view on parenteral nutrition.
AB  - Parenteral nutrition--a form of administering nutrients, electrolytes, trace
      elements, vitamins, and water--is a widely used mode of therapy applied in many
      diseases, in patients of different ages both at home and in hospital. The success
      of nutritional therapy depends chiefly on proper determination of the patient's
      energetic and electrolytic needs as well as preparation and administration of a
      safe nutritional mixture. As a parenterally administered drug, it is expected to
      be microbiologically and physicochemically stable, with all of the components
      compatible with each other. It is very difficult to obtain a stable nutritional
      mixture due to the fact that it is a complex, two-phase drug. Also, the risk of
      incompatibility between mixture components and packaging should be taken into
      consideration and possibly eliminated. Since parenteral nutrition is a part of
      therapy, simultaneous use of drugs may cause pharmacokinetic and pharmacodynamic
      interactions as well as those with the pharmaceutical phase. The aim of this
      paper is to discuss such aspects of parenteral nutrition as mixture stability,
      methodology, and methods for determining the stability of nutritional mixtures
      and drugs added to them.

PMID- 24453848
TI  - Anticancer activity of ferulic acid-inorganic nanohybrids synthesized via two
      different hybridization routes, reconstruction and exfoliation-reassembly.
AB  - We have successfully prepared nanohybrids of biofunctional ferulic acid and
      layered double hydroxide nanomaterials through reconstruction and exfoliation
      reassembly routes. From X-ray diffraction and infrared spectroscopy, both
      nanohybrids were determined to incorporate ferulic acid molecules in anionic
      form. Microscopic results showed that the nanohybrids had average particle size
      of 150 nm with plate-like morphology. As the two nanohybridization routes
      involved crystal disorder and random stacking of layers, the nanohybrids showed
      slight alteration in z-axis crystallinity and particle size. The zeta potential
      values of pristine and nanohybrids in deionized water were determined to be
      positive, while those in cell culture media shifted to negative values. According
      to the in vitro anticancer activity test on human cervical cancer HeLa cells, it
      was revealed that nanohybrids showed twice anticancer activity compared with
      ferulic acid itself. Therefore we could conclude that the nanohybrids of ferulic
      acid and layered double hydroxide had cellular delivery property of intercalated
      molecules on cancer cell lines.

PMID- 24453849
TI  - Electrochemical reduction of CO2 to organic acids by a Pd-MWNTs gas-diffusion
      electrode in aqueous medium.
AB  - Pd-multiwalled carbon nanotubes (Pd-MWNTs) catalysts for the conversion of CO2 to
      organic acids were prepared by the ethylene glycol reduction and fully
      characterized by Fourier transform infrared spectroscopy (FTIR), X-ray
      diffraction (XRD), transmission electron microscope (TEM), X-ray photoelectron
      spectroscopy (XPS), and cyclic voltammetry (CV) technologies. The amorphous Pd
      particles with an average size of 5.7 nm were highly dispersed on the surface of
      carbon nanotubes. Functional groups of the MWNTs played a key role in the
      palladium deposition. The results indicated that Pd-MWNTs could transform CO2
      into organic acid with high catalytic activity and CO2 could take part in the
      reduction reaction directly. Additionally, the electrochemical reduction of CO2
      was investigated by a diaphragm electrolysis device, using a Pd-MWNTs gas
      diffusion electrode as a cathode and a Ti/RuO2 net as an anode. The main products
      in present system were formic acid and acetic acid identified by ion
      chromatograph. The selectivity of the products could be achieved by reaction
      conditions changing. The optimum faraday efficiencies of formic and acetic acids
      formed on the Pd-MWNTs gas-diffusion electrode at 42V electrode voltages under 1
      atm CO2 were 34.5% and 52.3%, respectively.

PMID- 24453850
TI  - Sufficient condition on the fractional integral for the convergence of a
      function.
AB  - A sufficient condition on the fractional integral of the absolute value of a
      function is given in this paper, which allows to assure the convergence of the
      function to zero. This result can be useful to assure the convergence of a
      function when it is hard to know its exact evolution, but conditions on its
      fractional integral can be stated. 

PMID- 24453851
TI  - Synthesis characterization and antimicrobial activity studies of some transition
      metal complexes derived from 3-chloro-N'-[(1E)-(2-hydroxy phenyl)methylene]-6
      methoxy-1-benzothiophene-2-carbohydrazide.
AB  - A series of new coordination complexes of Cu(II), Co(II), Ni(II), Zn(II), Hg(II),
      Mn(II), and Fe(III) with the Schiff base 3-chloro-N'-[(1E)-(2-hydroxy
      phenyl)methylene]-6-methoxy-1-benzothiophene-2-carbohydrazide (HL) have been
      synthesized and characterized by elemental analysis, electrical conductivity
      measurements, IR spectra, (1)H NMR, mass spectral data, electronic spectra,
      magnetic susceptibility, ESR spectra, TGA, and Powder XRD data. The Schiff base
      behaves as tridentate ONO donor ligand and forms the complexes of the type ML2
      (metal-ligand) stoichiometry for Cu(II), Co(II), Ni(II), and Mn(II) complexes and
      ML stoichiometry for Zn(II), Hg(II), and Fe(III) complexes. All the complexes are
      colored and nonelectrolytes. It is found that Cu(II), Co(II), Ni(II), Mn(II) and
      Fe(III) complexes have exhibited octahedral geometry whereas Zn(II) and Hg(II)
      complexes exhibited tetrahedral geometry. The ligand and its metal complexes have
      been screened for their antibacterial activity against E. coli and S. aureus and
      antifungal activity against A. niger and A. flavus. 

PMID- 24453852
TI  - Quinolone prophylaxis in transrectal ultrasound guided prostate biopsy: an eight
      year single center experience.
AB  - We retrospectively evaluated the efficacy of prophylaxis with pipemidic acid and
      levofloxacin in transrectal ultrasound guided prostate biopsy (TRUSP-Bx). From
      January 2002 to December 2004, patients receiving oral pipemidic acid 500 mg
      twice daily for three days with or without a preoperative intravenous cefazolin 1
      gm injection comprised group A. Between January 2005 and December 2009, patients
      receiving oral levofloxacin 500 mg one hour before biopsy comprised group B. We
      calculated the annual febrile urinary tract infection (fUTI) rates. Patients'
      characteristics, including age, prophylactic antibiotics, biopsy core numbers,
      pathologic results, PSA, and the spectrums and susceptibility of pathogens, were
      also evaluated. A total of 1313 (35.5%) patients belonged to group A, while 2381
      (64.5%) patients belonged to group B. Seventy-three patients experienced
      postoperative infectious complications. There was a significant difference in the
      fUTI rate between groups A and B (3.7% versus 1.0%, P < 0.001). The yearly fUTI
      rates varied from 0.6 to 3.9% between 2002 and 2009. Of the 73 patients with
      fUTI, those receiving levofloxacin prophylaxis were more likely to harbor
      fluoroquinolone-resistant pathogens (P < 0.001). E. coli was the most common
      pathogen in both groups. Levofloxacin remains effective and appears superior to
      pipemidic acid based prophylaxis.

PMID- 24453853
TI  - A new gcrR-deficient Streptococcus mutans mutant for replacement therapy of
      dental caries.
AB  - BACKGROUND: gcrR gene acts as a negative regulator related to sucrose-dependent
      adherence in S. mutans. It is constructive to test the potential capacity of
      mutans with gcrR gene deficient in bacteria replacement therapy. METHODS: In this
      study, we constructed the mutant by homologous recombination. The morphological
      characteristics of biofilms were analyzed by confocal laser scanning microscopy.
      S. mutans UA159 and the mutant MS-gcrR-def were inoculated, respectively, or
      together for competitive testing in vitro and in rat model. RESULTS: Adhesion
      assay showed that the adhesion ability of the mutant increased relative to the
      wild type, especially in the early stage. MS-gcrR-def out-competed S. mutans
      UA159 in vitro biofilm, and correspondingly coinfection displayed significantly
      fewer caries in vivo. The former possessed both a lower level of acid production
      and a stronger colonization potential than S. mutans UA159. CONCLUSION: These
      findings demonstrate that MS-gcrR-def appears to be a good candidate for
      replacement therapy.

PMID- 24453854
TI  - Calcium oxide derived from waste shells of mussel, cockle, and scallop as the
      heterogeneous catalyst for biodiesel production.
AB  - The waste shell was utilized as a bioresource of calcium oxide (CaO) in
      catalyzing a transesterification to produce biodiesel (methyl ester). The
      economic and environmen-friendly catalysts were prepared by a calcination method
      at 700-1,000 degrees C for 4 h. The heterogeneous catalysts were characterized by
      X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy
      (SEM), and the Brunauer-Emmett-Teller (BET) method. The effects of reaction
      variables such as reaction time, reaction temperature, methanol/oil molar ratio,
      and catalyst loading on the yield of biodiesel were investigated. Reusability of
      waste shell catalyst was also examined. The results indicated that the CaO
      catalysts derived from waste shell showed good reusability and had high potential
      to be used as biodiesel production catalysts in transesterification of palm oil
      with methanol.

PMID- 24453855
TI  - The value of programmable shunt valves for the management of subdural collections
      in patients with hydrocephalus.
AB  - BACKGROUND: The aim of the present study was to assess the value of
      electromagnetic programmable shunt valves for the treatment of subdural
      collections. METHODS: Adult patients with hydrocephalus of various causes that
      were treated with programmable shunt valves during the last ten years were
      retrospectively studied. In 127 patients, 139 electromagnetic programmable shunt
      valves were implanted. RESULTS: A nontraumatic subdural fluid collection was
      detected in 12 patients. The treatment of these patients consisted of
      reprogramming of the valve's opening pressure. In 5 patients small subdural
      hematomas were detected; 4 of these patients were treated by raising the opening
      pressure alone and one patient required surgical drainage and change of the
      pressure setting. Traumatic chronic subdural hematomas were detected in 6
      patients. These patients were treated by surgical drainage and readjustment of
      the valve's opening pressure. CONCLUSION: The ability to treat a shunt-related
      complication, such as a subdural fluid collection, by reprogramming the valve's
      opening pressure to a higher setting is an advantage over nonprogrammable valves,
      and it enables the opening pressure to be slowly lowered once the fluid
      collection is reabsorbed. Based on our results, we believe that programmable
      shunt valves should be preferred.

PMID- 24453856
TI  - Joint estimation of 2D-DOA and frequency based on space-time matrix and conformal
      array.
AB  - Each element in the conformal array has a different pattern, which leads to the
      performance deterioration of the conventional high resolution direction-of
      arrival (DOA) algorithms. In this paper, a joint frequency and two-dimension DOA
      (2D-DOA) estimation algorithm for conformal array are proposed. The delay
      correlation function is used to suppress noise. Both spatial and time sampling
      are utilized to construct the spatial-time matrix. The frequency and 2D-DOA
      estimation are accomplished based on parallel factor (PARAFAC) analysis without
      spectral peak searching and parameter pairing. The proposed algorithm needs only
      four guiding elements with precise positions to estimate frequency and 2D-DOA.
      Other instrumental elements can be arranged flexibly on the surface of the
      carrier. Simulation results demonstrate the effectiveness of the proposed
      algorithm. 

PMID- 24453857
TI  - A graph theory practice on transformed image: a random image steganography.
AB  - Modern day information age is enriched with the advanced network communication
      expertise but unfortunately at the same time encounters infinite security issues
      when dealing with secret and/or private information. The storage and transmission
      of the secret information become highly essential and have led to a deluge of
      research in this field. In this paper, an optimistic effort has been taken to
      combine graceful graph along with integer wavelet transform (IWT) to implement
      random image steganography for secure communication. The implementation part
      begins with the conversion of cover image into wavelet coefficients through IWT
      and is followed by embedding secret image in the randomly selected coefficients
      through graph theory. Finally stegoimage is obtained by applying inverse IWT.
      This method provides a maximum of 44 dB peak signal to noise ratio (PSNR) for
      266646 bits. Thus, the proposed method gives high imperceptibility through high
      PSNR value and high embedding capacity in the cover image due to adaptive
      embedding scheme and high robustness against blind attack through graph theoretic
      random selection of coefficients.

PMID- 24453859
TI  - Adverse health effects and unhealthy behaviors among medical students using
      Facebook.
AB  - Little is known about the relationships between adverse health effects and
      unhealthy behaviors among medical students using Facebook. The aim of this study
      was to determine the associations between adverse health effects and unhealthy
      behaviors with Facebook use. A cross-sectional study was conducted in a private
      university in Malaysia among 316 medical students. A self-administered
      questionnaire was used. It included questions on sociodemographics, pattern of
      Facebook use, social relationship, unhealthy behaviors, and health effects. Mean
      age was 20.5 (+/-2.7) years. All students had a Facebook account. The average
      daily Facebook surfing hours were 2.5 (+/-1.7). Significant associations were
      found between average hours of Facebook surfing and the following factors:
      isolation from family members and community, refusing to answer calls,
      musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours
      spent on Facebook were significantly associated with holding urination and
      defecation while online, surfing Facebook until midnight, and postponing,
      forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook
      were associated with adverse health effects and unhealthy behaviors among medical
      students, as well as social isolation from the family and community.

PMID- 24453858
TI  - An evil backstage manipulator: psychological factors correlated with health
      related quality of life in Chinese patients with Crohn's disease.
AB  - Health-related quality of life (HRQoL) is recommended as one of essential
      parameters to evaluate treatment effect and clinical outcome in patients with
      Crohn's disease (CD). Recent studies reported that psychological factors might
      play a role in HRQoL in Western and American CD patients. Sufficient evidences in
      Chinese CD patients are still unavailable. This study is dedicated to investigate
      the correlation of various psychological factors with HRQoL in Chinese CD
      patients. We prospectively collected 40 active and 40 quiescent CD patients in
      China and found that psychological factors, especially neuroticism and anxiety,
      significantly correlate with and affect HRQoL in both active and quiescent CD
      groups. This is the first report revealing correlation between psychological
      factors and HRQoL in Chinese CD patients. Therefore, we assume that our results
      can contribute to a better understanding of etiology and tailoring of management
      in Chinese patients with Crohn's disease and are beneficial to our colleagues to
      compare the heterogeneous characteristics of Crohn's disease in different ethnic
      groups. 

PMID- 24453860
TI  - Electricity usage scheduling in smart building environments using smart devices.
AB  - With the recent advances in smart grid technologies as well as the increasing
      dissemination of smart meters, the electricity usage of every moment can be
      detected in modern smart building environments. Thus, the utility company adopts
      different price of electricity at each time slot considering the peak time. This
      paper presents a new electricity usage scheduling algorithm for smart buildings
      that adopts real-time pricing of electricity. The proposed algorithm detects the
      change of electricity prices by making use of a smart device and changes the
      power mode of each electric device dynamically. Specifically, we formulate the
      electricity usage scheduling problem as a real-time task scheduling problem and
      show that it is a complex search problem that has an exponential time complexity.
      An efficient heuristic based on genetic algorithms is performed on a smart device
      to cut down the huge searching space and find a reasonable schedule within a
      feasible time budget. Experimental results with various building conditions show
      that the proposed algorithm reduces the electricity charge of a smart building by
      25.6% on average and up to 33.4%. 

PMID- 24453861
TI  - Adaptive L1/2 shooting regularization method for survival analysis using gene
      expression data.
AB  - A new adaptive L1/2 shooting regularization method for variable selection based
      on the Cox's proportional hazards mode being proposed. This adaptive L1/2
      shooting algorithm can be easily obtained by the optimization of a reweighed
      iterative series of L1 penalties and a shooting strategy of L1/2 penalty.
      Simulation results based on high dimensional artificial data show that the
      adaptive L1/2 shooting regularization method can be more accurate for variable
      selection than Lasso and adaptive Lasso methods. The results from real gene
      expression dataset (DLBCL) also indicate that the L1/2 regularization method
      performs competitively.

PMID- 24453862
TI  - Explicit solutions of a gravity-induced film flow along a convectively heated
      vertical wall.
AB  - The gravity-driven film flow has been analyzed along a vertical wall subjected to
      a convective boundary condition. The Boussinesq approximation is applied to
      simplify the buoyancy term, and similarity transformations are used on the
      mathematical model of the problem under consideration, to obtain a set of coupled
      ordinary differential equations. Then the reduced equations are solved explicitly
      by using homotopy analysis method (HAM). The resulting solutions are investigated
      for heat transfer effects on velocity and temperature profiles. 

PMID- 24453863
TI  - An experimental investigation of sewage sludge gasification in a fluidized bed
      reactor.
AB  - The gasification of sewage sludge was carried out in a simple atmospheric
      fluidized bed gasifier. Flow and fuel feed rate were adjusted for experimentally
      obtaining an air mass : fuel mass ratio (A/F) of 0.2 < A/F < 0.4. Fuel
      characterization, mass and power balances, produced gas composition, gas phase
      alkali and ammonia, tar concentration, agglomeration tendencies, and gas
      efficiencies were assessed. Although accumulation of material inside the reactor
      was a main problem, this was avoided by removing and adding bed media along
      gasification. This allowed improving the process heat transfer and, therefore,
      gasification efficiency. The heating value of the produced gas was 8.4 MJ/Nm,
      attaining a hot gas efficiency of 70% and a cold gas efficiency of 57%.

PMID- 24453864
TI  - Fabrication and evaluation of porous beta-tricalcium phosphate/hydroxyapatite
      (60/40) composite as a bone graft extender using rat calvarial bone defect model.
AB  - Beta-tricalcium phosphate ( beta -TCP) and hydroxyapatite (HA) are widely used as
      bone graft extenders due to their osteoconductivity and high bioactivity. This
      study aims to evaluate the possibility of using porous substrate with composite
      ceramics ( beta -TCP: HA = 60% : 40%, 60TCP40HA) as a bone graft extender and
      comparing it with Bio-Oss. Interconnectivity and macroporosity of beta -TCP
      porous substrate were 99.9% and 83%, respectively, and the macro-porosity of
      packed granule after crushing was 69%. Calvarial defect model with 8 mm diameter
      was generated with male Sprague-Dawley rats and 60TCP40HA was implanted. Bio-Oss
      was implanted for a control group and micro-CT and histology were performed at 4
      and 8 weeks after implantation. The 60TCP40HA group showed better new bone
      formation than the Bio-Oss group and the bone formation at central area of bone
      defect was increased at 8 weeks in micro-CT and histology. The percent bone
      volume and trabecular number of the 60TCP40HA group were significantly higher
      than those of Bio-Oss group. This study confirms the usefulness of the porous
      60TCP40HA composite as a bone graft extender by showing increased new bone
      formation in the calvarial defect model and improved bone formation both
      quantitatively and qualitatively when compared to Bio-Oss.

PMID- 24453865
TI  - Sequential bearings-only-tracking initiation with particle filtering method.
AB  - The tracking initiation problem is examined in the context of autonomous bearings
      only-tracking (BOT) of a single appearing/disappearing target in the presence of
      clutter measurements. In general, this problem suffers from a combinatorial
      explosion in the number of potential tracks resulted from the uncertainty in the
      linkage between the target and the measurement (a.k.a the data association
      problem). In addition, the nonlinear measurements lead to a non-Gaussian
      posterior probability density function (pdf) in the optimal Bayesian sequential
      estimation framework. The consequence of this nonlinear/non-Gaussian context is
      the absence of a closed-form solution. This paper models the linkage uncertainty
      and the nonlinear/non-Gaussian estimation problem jointly with solid Bayesian
      formalism. A particle filtering (PF) algorithm is derived for estimating the
      model's parameters in a sequential manner. Numerical results show that the
      proposed solution provides a significant benefit over the most commonly used
      methods, IPDA and IMMPDA. The posterior Cramer-Rao bounds are also involved for
      performance evaluation.

PMID- 24453866
TI  - Management of gastric varices unsuccessfully treated by balloon-occluded
      retrograde transvenous obliteration: long-term follow-up and outcomes.
AB  - Our aim was to evaluate the long-term efficacy and safety of percutaneous
      transhepatic obliteration (PTO) alone and combined with balloon-occluded
      retrograde transvenous obliteration (BRTO) for gastroesophageal varices
      refractory to BRTO alone. Between July 1999 and December 2010, 13 patients with
      gastroesophageal varices refractory to BRTO were treated with PTO (n = 6) or a
      combination of PTO and BRTO (n = 7). We retrospectively investigated the rates of
      survival, recurrence, or worsening of the varices; hepatic function before and
      after the procedure; and complications. The procedure achieved complete
      obliteration or significant reduction of the varices in all 13 patients without
      major complications. During follow-up, the varices had recurred in 2 patients, of
      which one had hepatocellular carcinoma, and the other died suddenly from variceal
      rebleeding 7 years after PTO. The remaining 11 patients did not experience
      worsening of the varices and showed significant improvements in the serum ammonia
      levels and prothrombin time. The mean follow-up period was 90 months, and the
      cumulative survival rate at 1, 3, and 5 years was 92.9%, 85.7%, and 85.7%,
      respectively. Both PTO and combined PTO and BRTO seem as safe and effective
      procedures for the treatment of gastroesophageal varices refractory to BRTO
      alone.

PMID- 24453867
TI  - Blood clot simulation model by using the Bond-Graph technique.
AB  - The World Health Organization estimates that 17 million people die of
      cardiovascular disease, particularly heart attacks and strokes, every year. Most
      strokes are caused by a blood clot that occludes an artery in the cerebral
      circulation and the process concerning the removal of this obstruction involves
      catheterisation. The fundamental object of the presented study consists in
      determining and optimizing the necessary simulation model corresponding with the
      blood clot zone to be implemented jointly with other Mechanical Thrombectomy
      Device simulation models, which have become more widely used during the last
      decade. To do so, a multidomain technique is used to better explain the different
      aspects of the attachment to the artery wall and between the existing platelets,
      it being possible to obtain the mathematical equations that define the full
      model. For a better understanding, a consecutive approximation to the definitive
      model will be presented, analyzing the different problems found during the study.
      The final presented model considers an elastic characterization of the blood clot
      composition and the possibility of obtaining a consecutive detachment process
      from the artery wall. In conclusion, the presented model contains the necessary
      behaviour laws to be implemented in future blood clot simulation models. 

PMID- 24453868
TI  - Multiscale medical image fusion in wavelet domain.
AB  - Wavelet transforms have emerged as a powerful tool in image fusion. However, the
      study and analysis of medical image fusion is still a challenging area of
      research. Therefore, in this paper, we propose a multiscale fusion of multimodal
      medical images in wavelet domain. Fusion of medical images has been performed at
      multiple scales varying from minimum to maximum level using maximum selection
      rule which provides more flexibility and choice to select the relevant fused
      images. The experimental analysis of the proposed method has been performed with
      several sets of medical images. Fusion results have been evaluated subjectively
      and objectively with existing state-of-the-art fusion methods which include
      several pyramid- and wavelet-transform-based fusion methods and principal
      component analysis (PCA) fusion method. The comparative analysis of the fusion
      results has been performed with edge strength (Q), mutual information (MI),
      entropy (E), standard deviation (SD), blind structural similarity index metric
      (BSSIM), spatial frequency (SF), and average gradient (AG) metrics. The combined
      subjective and objective evaluations of the proposed fusion method at multiple
      scales showed the effectiveness and goodness of the proposed approach. 

PMID- 24453869
TI  - Optimal filtering methods to structural damage estimation under ground
      excitation.
AB  - This paper considers the problem of shear building damage estimation subject to
      earthquake ground excitation using the Kalman filtering approach. The structural
      damage is assumed to take the form of reduced elemental stiffness. Two damage
      estimation algorithms are proposed: one is the multiple model approach via the
      optimal two-stage Kalman estimator (OTSKE), and the other is the robust two-stage
      Kalman filter (RTSKF), an unbiased minimum-variance filtering approach to
      determine the locations and extents of the damage stiffness. A numerical example
      of a six-storey shear plane frame structure subject to base excitation is used to
      illustrate the usefulness of the proposed results. 

PMID- 24453870
TI  - Capped fluorescent carbon dots for detection of hemin: role of number of -OH
      groups of capping agent in fluorescence quenching.
AB  - We have successfully demonstrated the use of capped carbon dot systems, namely,
      CDs/ beta -cd, CDs/LMH, and CDs/Suc, as fluorescent sensors for the detection of
      hemin. The capped carbon dot systems showed quenching of PL intensity in the
      presence of hemin. The minimum detection limit was determined to be ~1 MU M. The
      PL response with free Fe(II) and Fe(III) was also studied. It was observed that
      PL quenching of capped carbon dot systems in the presence of hemin is dependent
      on the number of -OH groups in the capping agent. The order of quenching towards
      hemin was determined to be CDs/ beta -cd > CDs/LMH = CDs/Suc > CDs. A possible
      mechanism to account for the observation is also discussed in the paper.

PMID- 24453871
TI  - Cotton-type and joint invariants for linear elliptic systems.
AB  - Cotton-type invariants for a subclass of a system of two linear elliptic
      equations, obtainable from a complex base linear elliptic equation, are derived
      both by spliting of the corresponding complex Cotton invariants of the base
      complex equation and from the Laplace-type invariants of the system of linear
      hyperbolic equations equivalent to the system of linear elliptic equations via
      linear complex transformations of the independent variables. It is shown that
      Cotton-type invariants derived from these two approaches are identical.
      Furthermore, Cotton-type and joint invariants for a general system of two linear
      elliptic equations are also obtained from the Laplace-type and joint invariants
      for a system of two linear hyperbolic equations equivalent to the system of
      linear elliptic equations by complex changes of the independent variables.
      Examples are presented to illustrate the results. 

PMID- 24453872
TI  - A hybrid approach for short-term forecasting of wind speed.
AB  - We propose a hybrid method for forecasting the wind speed. The wind speed data is
      first decomposed into intrinsic mode functions (IMFs) with empirical mode
      decomposition. Based on the partial autocorrelation factor of the individual
      IMFs, adaptive methods are then employed for the prediction of IMFs. Least
      squares-support vector machines are employed for IMFs with weak correlation
      factor, and autoregressive model with Kalman filter is employed for IMFs with
      high correlation factor. Multistep prediction with the proposed hybrid method
      resulted in improved forecasting. Results with wind speed data show that the
      proposed method provides better forecasting compared to the existing methods. 

PMID- 24453874
TI  - Phase-field simulations at the atomic scale in comparison to molecular dynamics.
AB  - Early solidification is investigated using two different simulation techniques:
      the molecular dynamics (MD) and the phase-field (PF) methods. While the first
      describes the evolution of a system on the basis of motion equations of
      particles, the second grounds on the evolution of continuous local order
      parameter field. The aim of this study is to probe the ability of the mesoscopic
      phase-field method to make predictions of growth velocity at the nanoscopic
      length scale. For this purpose the isothermal growth of a spherical crystalline
      cluster embedded in a melt is considered. The system in study is Ni modeled with
      the embedded atom method (EAM). The bulk and interfacial properties required in
      the PF method are obtained from MD simulations. Also the initial configuration
      obtained from MD data is used in the PF as input. Results for the evolution of
      the cluster volume at high and moderate undercooling are presented.

PMID- 24453873
TI  - Associates of an elevated natriuretic peptide level in stable heart failure
      patients: implications for targeted management.
AB  - BACKGROUND: Persistently elevated natriuretic peptide (NP) levels in heart
      failure (HF) patients are associated with impaired prognosis. Recent work
      suggests that NP-guided therapy can improve outcome, but the mechanisms behind an
      elevated BNP remain unclear. Among the potential stimuli for NP in clinically
      stable patients are persistent occult fluid overload, wall stress, inflammation,
      fibrosis, and ischemia. The purpose of this study was to identify associates of B
      type natriuretic peptide (BNP) in a stable HF population. METHODS: In a
      prospective observational study of 179 stable HF patients, the association
      between BNP and markers of collagen metabolism, inflammation, and Doppler
      echocardiographic parameters including left ventricular ejection fraction (LVEF),
      left atrial volume index (LAVI), and E/e prime (E/e') was measured. RESULTS:
      Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine,
      and markers of collagen turnover. In a multiple linear regression model, age,
      creatinine, and LVEF remained significant associates of BNP. E/e' and markers of
      collagen turnover had a persistent impact on BNP independent of these covariates.
      CONCLUSION: Multiple variables are associated with persistently elevated BNP
      levels in stable HF patients. Clarification of the relative importance of NP
      stimuli may help refine NP-guided therapy, potentially improving outcome for this
      at-risk population.

PMID- 24453875
TI  - Removal of sulfur dioxide from flue gas using the sludge sodium humate.
AB  - This study shows the ability of sodium humate from alkaline treatment sludge on
      removing sulfur dioxide (SO2) in the simulated flue gas. Experiments were
      conducted to examine the effect of various operating parameters, like the inlet
      SO2 concentration or temperature or O2, on the SO2 absorption efficiency and
      desulfurization time in a lab-scale bubbling reactor. The sludge sodium humate in
      the supernatant after alkaline sludge treatment shows great performance in SO2
      absorption, and such efficiency can be maintained above 98% with 100 mL of this
      absorption solution at 298 K (flue gas rate of 0.12 m(3)/h). The highest SO2
      absorption by 1.63 g SHA-Na is 0.946 mmol in the process, which is translated to
      0.037 g SO2 g(-1) SHA-Na. The experimental results indicate that the inlet SO2
      concentration slightly influences the SO2 absorption efficiency and significantly
      influences the desulfurization time. The pH of the absorption solution should be
      above 3.5 in this process in order to make an effective desulfurization. The
      products of this process were characterized by Fourier transform infrared
      spectroscopy and X-ray diffraction. It can be seen that the desulfurization
      products mainly contain sludge humic acid sediment, which can be used as
      fertilizer components.

PMID- 24453876
TI  - Prediction of missing flow records using multilayer perceptron and coactive
      neurofuzzy inference system.
AB  - Hydrological data are often missing due to natural disasters, improper operation,
      limited equipment life, and other factors, which limit hydrological analysis.
      Therefore, missing data recovery is an essential process in hydrology. This paper
      investigates the accuracy of artificial neural networks (ANN) in estimating
      missing flow records. The purpose is to develop and apply neural networks models
      to estimate missing flow records in a station when data from adjacent stations is
      available. Multilayer perceptron neural networks model (MLP) and coactive
      neurofuzzy inference system model (CANFISM) are used to estimate daily flow
      records for Li-Lin station using daily flow data for the period 1997 to 2009 from
      three adjacent stations (Nan-Feng, Lao-Nung and San-Lin) in southern Taiwan. The
      performance of MLP is slightly better than CANFISM, having R (2) of 0.98 and
      0.97, respectively. We conclude that accurate estimations of missing flow records
      under the complex hydrological conditions of Taiwan could be attained by
      intelligent methods such as MLP and CANFISM. 

PMID- 24453877
TI  - Robust human machine interface based on head movements applied to assistive
      robotics.
AB  - This paper presents an interface that uses two different sensing techniques and
      combines both results through a fusion process to obtain the minimum-variance
      estimator of the orientation of the user's head. Sensing techniques of the
      interface are based on an inertial sensor and artificial vision. The orientation
      of the user's head is used to steer the navigation of a robotic wheelchair. Also,
      a control algorithm for assistive technology system is presented. The system is
      evaluated by four individuals with severe motors disability and a quantitative
      index was developed, in order to objectively evaluate the performance. The
      results obtained are promising since most users could perform the proposed tasks
      with the robotic wheelchair. 

PMID- 24453878
TI  - Lumbar spinal stenosis has a negative impact on quality of life compared with
      other comorbidities: an epidemiological cross-sectional study of 1862 community
      dwelling individuals.
AB  - Lumbar spinal stenosis (LSS) is common in the elderly. However, there have been
      few reports on its impact on quality of life (QoL) in community-dwelling
      individuals. The purpose of this study was to clarify how symptomatic LSS affects
      QoL at the community level. A total of 1862 people (697 males and 1165 females,
      most subjects were between 40 and 85 y.o.) agreed to participate and were
      interviewed. The presence of symptomatic LSS was assessed by a specially designed
      questionnaire. The Medical Outcomes Study 36-Item Short Form Health Survey (SF
      36) was also administered. In addition, the presence of comorbid conditions that
      affect QoL, such as osteoarthritis of the knee and hip, cardiovascular disease,
      cerebrovascular disease, or respiratory disease, was also analyzed. The
      prevalence of symptomatic LSS gradually increased with age. Furthermore, the
      presence of symptomatic LSS had a strong negative effect on all 8 physical and
      mental domains and the physical component summary (PCS) (OR: 1.547-2.544) but not
      the mental component summary (MCS). In comparison with comorbid conditions, LSS
      had a much stronger negative impact on health-related QoL (HR-QoL). The current
      study confirmed that the presence of symptomatic LSS might have a strong negative
      influence on HR-QoL in the community setting. 

PMID- 24453879
TI  - Characteristics and outcomes of elderly patients refused to ICU.
AB  - BACKGROUND: There are few data regarding the process of deciding which elderly
      patients are refused to ICU admission, their characteristics, and outcome.
      METHODS: Prospective longitudinal observational cohort study. We included all
      consecutive patients older than 75 years, who were evaluated for admission to but
      were refused to treatment in ICU, during 18 months, with 12-month followup. We
      collected demographic data, ICU admission/refusal reasons, previous functional
      and cognitive status, comorbidity, severity of illness, and hospital and 12-month
      mortality. RESULTS: 338 elderly patients were evaluated for ICU admission and 88
      were refused to ICU (26%). Patients refused because they were "too ill to
      benefit" had more comorbidity and worse functional and mental situation than
      those admitted to ICU; there were no differences in illness severity. Hospital
      mortality rate of the whole study cohort was 36.3%, higher in patients "too ill
      to benefit" (55.6% versus 35.8%, P < 0.01), which also have higher 1-year
      mortality (73.7% versus 42.5%, P < 0.01). High comorbidity, low functional
      status, unavailable ICU beds, and age were associated with refusal decision on
      multivariate analysis. CONCLUSIONS: Prior functional status and comorbidity, not
      only the age or severity of illness, can help us more to make the right decision
      of admitting or refusing to ICU patients older than 75 years.

PMID- 24453881
TI  - Synthesis of trigeneration systems: sensitivity analyses and resilience.
AB  - This paper presents sensitivity and resilience analyses for a trigeneration
      system designed for a hospital. The following information is utilized to
      formulate an integer linear programming model: (1) energy service demands of the
      hospital, (2) technical and economical characteristics of the potential
      technologies for installation, (3) prices of the available utilities
      interchanged, and (4) financial parameters of the project. The solution of the
      model, minimizing the annual total cost, provides the optimal configuration of
      the system (technologies installed and number of pieces of equipment) and the
      optimal operation mode (operational load of equipment, interchange of utilities
      with the environment, convenience of wasting cogenerated heat, etc.) at each
      temporal interval defining the demand. The broad range of technical, economic,
      and institutional uncertainties throughout the life cycle of energy supply
      systems for buildings makes it necessary to delve more deeply into the
      fundamental properties of resilient systems: feasibility, flexibility and
      robustness. The resilience of the obtained solution is tested by varying, within
      reasonable limits, selected parameters: energy demand, amortization and
      maintenance factor, natural gas price, self-consumption of electricity, and time
      of-delivery feed-in tariffs. 

PMID- 24453880
TI  - Phenolic profile of dark-grown and photoperiod-exposed Hypericum perforatum L.
      Hairy root cultures.
AB  - Hypericum perforatum L. is a medicinal plant considered as an important natural
      source of secondary metabolites with a wide range of pharmacological attributes.
      Hairy roots (HR) were induced from root segments of in vitro grown seedlings from
      H. perforatum after cocultivation with Agrobacterium rhizogenes A4.
      Investigations have been made to study the production of phenolic compounds in
      dark-grown (HR1) and photoperiod-exposed (HR2) cultures. The chromatographic
      analysis of phenolic acids, flavonols, flavan-3-ols, and xanthones revealed
      marked differences between HR1 and HR2 cultures. The production of quinic acid,
      kaempferol, and seven identified xanthones was increased in HR2. Moreover, HR2
      showed a capability for de novo biosynthesis of two phenolic acids (3-p
      coumaroylquinic acid and 3-feruloylquinic acid), three flavonol glycosides
      (kaempferol hexoside, hyperoside, and quercetin acetylglycoside), and five
      xanthones (tetrahydroxy-one-methoxyxanthone, 1,3,5-trihydroxy-6-methoxyxanthone,
      1,3,5,6-tetrahydroxy-2-prenylxanthone, paxanthone, and banaxanthone E). On the
      other side, HR1 cultures were better producers of flavan-3-ols (catechin,
      epicatechin, and proanthocyanidin dimers) than HR2. This is the first comparative
      study on phenolic profile of H. perforatum HR cultures grown under dark and
      photoperiod conditions. 

PMID- 24453882
TI  - Hydrogeological conditions of a crystalline aquifer: simulation of optimal
      abstraction rates under scenarios of reduced recharge.
AB  - A steady state numerical groundwater flow model has been calibrated to
      characterize the spatial distribution of a key hydraulic parameter in a
      crystalline aquifer in southwestern Ghana. This was to provide an initial basis
      for characterizing the hydrogeology of the terrain with a view to assisting in
      the large scale development of groundwater resources for various uses. The
      results suggest that the structural entities that control groundwater occurrence
      in the area are quite heterogeneous in their nature and orientation, ascribing
      hydraulic conductivity values in the range of 4.5 m/d to over 70 m/d to the
      simulated aquifer. Aquifer heterogeneities, coupled possibly with topographical
      trends, have led to the development of five prominent groundwater flowpaths in
      the area. Estimated groundwater recharge at calibration ranges between 0.25% and
      9.13% of the total annual rainfall and appears to hold significant promise for
      large-scale groundwater development to support irrigation schemes. However, the
      model suggests that with reduced recharge by up to 30% of the current rates, the
      system can only sustain increased groundwater abstraction by up to 150% of the
      current abstraction rates. Prudent management of the resource will require a much
      more detailed hydrogeological study that identifies all the aquifers in the basin
      for the assessment of sustainable basin yield.

PMID- 24453883
TI  - Risk assessment of groundwater contamination: a multilevel fuzzy comprehensive
      evaluation approach based on DRASTIC model.
AB  - Groundwater contamination is a serious threat to water supply. Risk assessment of
      groundwater contamination is an effective way to protect the safety of
      groundwater resource. Groundwater is a complex and fuzzy system with many
      uncertainties, which is impacted by different geological and hydrological
      factors. In order to deal with the uncertainty in the risk assessment of
      groundwater contamination, we propose an approach with analysis hierarchy process
      and fuzzy comprehensive evaluation integrated together. Firstly, the risk factors
      of groundwater contamination are identified by the sources-pathway-receptor
      consequence method, and a corresponding index system of risk assessment based on
      DRASTIC model is established. Due to the complexity in the process of transitions
      between the possible pollution risks and the uncertainties of factors, the method
      of analysis hierarchy process is applied to determine the weights of each factor,
      and the fuzzy sets theory is adopted to calculate the membership degrees of each
      factor. Finally, a case study is presented to illustrate and test this
      methodology. It is concluded that the proposed approach integrates the advantages
      of both analysis hierarchy process and fuzzy comprehensive evaluation, which
      provides a more flexible and reliable way to deal with the linguistic uncertainty
      and mechanism uncertainty in groundwater contamination without losing important
      information. 

PMID- 24453884
TI  - Seismic microzonation of Breginjski kot (NW Slovenia) based on detailed
      engineering geological mapping.
AB  - Breginjski kot is among the most endangered seismic zones in Slovenia with the
      seismic hazard assessed to intensity IX MSK and the design ground acceleration of
      0.250 g, both for 500-year return period. The most destructive was the 1976
      Friuli Mw = 6.4 earthquake which had maximum intensity VIII-IX. Since the
      previous microzonation of the area was based solely on the basic geological map
      and did not include supplementary field research, we have performed a new soil
      classification of the area. First, a detailed engineering geological mapping in
      scale 1 : 5.000 was conducted. Mapped units were described in detail and some of
      them interpreted anew. Stiff sites are composed of hard to medium-hard rocks
      which were subjected to erosion mainly evoked by glacial and postglacial age. At
      that time a prominent topography was formed and different types of sediments were
      deposited in valleys by mass flows. A distinction between sediments and weathered
      rocks, their exact position, and thickness are of significant importance for
      microzonation. On the basis of geological mapping, a soil classification was
      carried out according to the Medvedev method (intensity increments) and the
      Eurocode 8 standard (soil factors) and two microzonation maps were prepared. The
      bulk of the studied area is covered by soft sediments and nine out of ten
      settlements are situated on them. The microzonation clearly points out the
      dependence of damage distribution in the case of 1976 Friuli earthquake to local
      site effects.

PMID- 24453885
TI  - Microbial fuel cells for direct electrical energy recovery from urban
      wastewaters.
AB  - Application of microbial fuel cells (MFCs) to wastewater treatment for direct
      recovery of electric energy appears to provide a potentially attractive
      alternative to traditional treatment processes, in an optic of costs reduction,
      and tapping of sustainable energy sources that characterizes current trends in
      technology. This work focuses on a laboratory-scale, air-cathode, and single
      chamber MFC, with internal volume of 6.9 L, operating in batch mode. The MFC was
      fed with different types of substrates. This study evaluates the MFC behaviour,
      in terms of organic matter removal efficiency, which reached 86% (on average)
      with a hydraulic retention time of 150 hours. The MFC produced an average power
      density of 13.2 mW/m(3), with a Coulombic efficiency ranging from 0.8 to 1.9%.
      The amount of data collected allowed an accurate analysis of the repeatability of
      MFC electrochemical behaviour, with regards to both COD removal kinetics and
      electric energy production.

PMID- 24453886
TI  - Solvation effects on the static and dynamic first-order electronic and
      vibrational hyperpolarizabilities of uracil: a polarized continuum model
      investigation.
AB  - Electronic (beta(e)) and vibrational (beta(v)) first-order hyperpolarizabilities
      of uracil were determined in gas and water solution using the Coulomb-attenuating
      Density Functional Theory level with the Dunning's correlation-consistent aug-cc
      pVDZ basis set. Frequency-dependent beta(e) values were computed for the Second
      Harmonic Generation (SHG) and Electric Optical Pockels Effect (EOPE) nonlinear
      optical phenomena. The Polarized Continuum Model was employed to study the
      solvent effects on the electronic and vibrational properties. The introduction of
      solvation contributions increases the beta(e) (static) value by ca. 110%. In
      comparison, smaller enhancements are found for the beta(e) (EOPE) and beta(e)
      (SHG) data evaluated at the typical wavelength of 694 nm (by 40-50%). The gas
      water hyperpolarizability difference was rationalised through a density analysis
      study. The magnitudes of the vibrational first-order hyperpolarizabilities are
      comparable to their electronic counterparts and noticeably increase in solution:
      beta(v) (EOPE) ~ beta(e) (EOPE) in aqueous phase at lambda = 694 nm. Analysis of
      the IR and Raman spectra is useful to elucidate the most important contributing
      modes to the vibrational first-order hyperpolarizabilities.

PMID- 24453888
TI  - Comparative study of understorey birds diversity inhabiting lowland rainforest
      virgin jungle reserve and regenerated forest.
AB  - A comparative study of understorey birds inhabiting different habitats, that is,
      virgin jungle reserve (VJR) and regenerated forest (RF), was conducted in Ulu
      Gombak Forest Reserve and Selangor and Triang Forest Reserve, Negeri Sembilan,
      Peninsular Malaysia. The objective of this study was to assess the diversity of
      understorey birds in both habitats and the effects of forest regeneration on the
      understorey bird community. The mist-netting method was used to capture
      understorey birds inhabiting both habitats in both locations. Species composition
      and feeding guild indicated that understorey bird populations were similar in the
      two habitats. However, the number of secondary forest species such as Little
      spiderhunter (Arachnothera longirostra) in VJR is increasing due to its proximity
      to RF. This study discovered that RFs in both study areas are not yet fully
      recovered. However, based on the range of species discovered, the RFs have
      conservation value and should be maintained because they harbour important forest
      species such as babblers and flycatchers. The assessment of the community
      structure of understorey birds in VJR and RF is important for forest management
      and conservation, especially where both habitats are intact. 

PMID- 24453887
TI  - Genetic variants of neurotransmitter-related genes and miRNAs in Egyptian
      autistic patients.
AB  - Autism is a neurodevelopmental disorder with indisputable evidence for a genetic
      component. This work studied the association of autism with genetic variations in
      neurotransmitter-related genes, including MAOA uVNTR, MAOB rs1799836, and DRD2
      TaqI A in 53 autistic patients and 30 healthy individuals. The study also
      analyzed sequence variations of miR-431 and miR-21. MAOA uVNTR was genotyped by
      PCR, MAOB and DRD2 polymorphisms were analyzed by PCR-based RFLP, and miR-431 and
      miR-21 were sequenced. Low expressing allele of MAOA uVNTR was frequently higher
      in female patients compared to that in controls (OR = 2.25). MAOB G allele
      frequency was more significantly increased in autistic patients than in controls
      (P < 0.001 for both males and females). DRD2 A1+ genotype increased autism risk
      (OR = 5.1). Severity of autism tends to be slightly affected by MAOA/B genotype.
      Plasma MAOB activity was significantly reduced in G than in A allele carrying
      males. There was no significant difference in patients and maternal plasma MAOA/B
      activity compared to controls. Neither mutations nor SNPs in miR-431 and miR-21
      were found among studied patients. This study threw light on some
      neurotransmitter-related genes suggesting their potential role in Autism
      pathogenesis that warrants further studies and much consideration. 

PMID- 24453889
TI  - New urea and thiourea derivatives of piperazine doped with febuxostat: synthesis
      and evaluation of anti-TMV and antimicrobial activities.
AB  - A series of new 4-(5-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-2-carbonyl)-N
      (substituted phenyl)piperazine-1-carboxamides 8(a-e)/carbothioamides 8(f-j) were
      accomplished for biological interest by the simple addition of active
      functionalized arylisocyanates 7(a-e)/arylisothiocyanates 7(f-j) with 2-isobutoxy
      5-(4-methyl-2-(piperazine-1-carbonyl)thiazol-5-yl)benzonitrile (4). Compound 4
      was synthesized in high yields (94%) by the condensation reaction of febuxostat
      (1) with piperazine using a selective reagent such as propylphosphonic anhydride
      (T3P). Antiviral activity against Tobacco mosaic virus (TMV) and antimicrobial
      activity of the synthesized compounds were evaluated. Biological data revealed
      that 4-nitrophenyl substituted urea 8d, and 3-bromophenyl substituted thiourea 8f
      exhibited promising antiviral activities. Moreover, 4-fluorophenyl substituted
      urea 8a, 4-nitrophenyl substituted urea 8d, 3-bromophenyl substituted thiourea
      8f, and 2,4-dichlorophenyl substituted thiourea 8j exhibited potent antimicrobial
      activity. 

PMID- 24453890
TI  - An effective cache algorithm for heterogeneous storage systems.
AB  - Modern storage environment is commonly composed of heterogeneous storage devices.
      However, traditional cache algorithms exhibit performance degradation in
      heterogeneous storage systems because they were not designed to work with the
      diverse performance characteristics. In this paper, we present a new cache
      algorithm called HCM for heterogeneous storage systems. The HCM algorithm
      partitions the cache among the disks and adopts an effective scheme to balance
      the work across the disks. Furthermore, it applies benefit-cost analysis to
      choose the best allocation of cache block to improve the performance. Conducting
      simulations with a variety of traces and a wide range of cache size, our
      experiments show that HCM significantly outperforms the existing state-of-the-art
      storage-aware cache algorithms. 

PMID- 24453891
TI  - Anticonvulsant effect of Diazoxide against Dichlorvos-induced seizures in mice.
AB  - Dichlorvos, a synthetic organophosphate toxin, is used as pesticides. These
      toxins can be used as pesticides in farming and medicine for the devastation
      and/or elimination of ectoparasites of animals. Reports have shown that
      Dichlorvos generate seizure effects in various animals. Potassium channel opener
      is extensively used for medication of cardiovascular and other diseases. Studies
      have shown that potassium channel opener has anticonvulsant effects in different
      animal models. The goal of this study was to evaluate the effect of dizoxide on
      Dichlorvos-induced seizures in mice. In this research, the animals received
      different doses of Diazoxide (1, 2.5, 5, 10, and 20 mg/kg b.wt.)
      intraperitoneally 30 min before intraperitoneal injection of Dichlorvos (50 mg/kg
      b.w.t). After Dichlorvos injection, latency of clones, severity of seizure, and
      finally death as the fate were investigated. Results showed that Diazoxide dose
      dependently decreased the severity of Dichlorvos-induced seizures, so that
      Diazoxide at a dose of 5 mg (the lowest, P < 0.05) and 20 mg/kg b.wt. (the
      highest, P < 0.001) has anticonvulsant effects. Thus, our data suggest that
      diazoxide as ATP-sensitive potassium channels opener has anticonvulsant activity
      against dichlorvas-induced seizure.

PMID- 24453892
TI  - Multiple-feature extracting modules based leak mining system design.
AB  - Over the years, human dependence on the Internet has increased dramatically. A
      large amount of information is placed on the Internet and retrieved from it
      daily, which makes web security in terms of online information a major concern.
      In recent years, the most problematic issues in web security have been e-mail
      address leakage and SQL injection attacks. There are many possible causes of
      information leakage, such as inadequate precautions during the programming
      process, which lead to the leakage of e-mail addresses entered online or
      insufficient protection of database information, a loophole that enables
      malicious users to steal online content. In this paper, we implement a crawler
      mining system that is equipped with SQL injection vulnerability detection, by
      means of an algorithm developed for the web crawler. In addition, we analyze
      portal sites of the governments of various countries or regions in order to
      investigate the information leaking status of each site. Subsequently, we analyze
      the database structure and content of each site, using the data collected. Thus,
      we make use of practical verification in order to focus on information security
      and privacy through black-box testing. 

PMID- 24453893
TI  - Sustainable power generation in continuous flow microbial fuel cell treating
      actual wastewater: influence of biocatalyst type on electricity production.
AB  - Microbial fuel cells (MFCs) have the potential to simultaneously treat wastewater
      for reuse and to generate electricity. This study mainly considers the
      performance of an upflow dual-chambered MFC continuously fueled with actual
      domestic wastewater and alternatively biocatalyzed with aerobic activated sludge
      and strain of Bacillus Subtilis. The behavior of MFCs during initial biofilm
      growth and characterization of anodic biofilm were studied. After 45 days of
      continuous operation, the biofilms on the anodic electrode were well developed.
      The performance of MFCs was mainly evaluated in terms of COD reductions and
      electrical power output. Results revealed that the COD removal efficiency was 84%
      and 90% and the stabilized power outputs were clearly observed achieving a
      maximum value of 120 and 270 mW/m(2) obtained for MFCs inoculated with mixed
      cultures and Bacillus Subtilis strain, respectively.

PMID- 24453894
TI  - Peroxidase(s) in environment protection.
AB  - Industrial discharges of untreated effluents into water bodies and emissions into
      air have deteriorated the quality of water and air, respectively. The huge amount
      of pollutants derived from industrial activities represents a threat for the
      environment and ecologic equilibrium. Phenols and halogenated phenols, polycyclic
      aromatic hydrocarbons (PAH), endocrine disruptive chemicals (EDC), pesticides,
      dioxins, polychlorinated biphenyls (PCB), industrial dyes, and other xenobiotics
      are among the most important pollutants. Peroxidases are enzymes that are able to
      transform a variety of compounds following a free radical mechanism, thereby
      yielding oxidized or polymerized products. The peroxidase transformation of these
      pollutants is accompanied by a reduction in their toxicity, due to loss of
      biological activity, reduction in the bioavailability, or the removal from
      aqueous phase, especially when the pollutant is found in water. The review
      describes the sources of peroxidases, the reactions catalyzed by them, and their
      applications in the management of pollutants in the environment. 

PMID- 24453896
TI  - Influence of niobium on the beginning of the plastic flow of material during cold
      deformation.
AB  - Investigations were conducted on low-carbon steel and the steel with same
      chemical composition with addition of microalloying element niobium. While
      tensile testing was carried out, the thermographic measurement was tacking place
      simultaneously. A specific behavior of niobium microalloyed steel was noticed.
      Test results have shown that, in the elastic deformation region, thermoelastic
      effect occurs, which is more pronounced in niobium microalloyed steel. Start of
      plastic flow in steel which is not microalloyed with niobium begins later in
      comparison to the microalloyed steel, and it is conducted so that, at the point
      of maximum stress, deformation zone is formed within which stresses grow. In
      steel microalloyed with niobium after proportionality limit, comes the occurrence
      of the localized increase in temperature and the occurrence of Luders band, which
      propagate along the sample forming a deformation zone. 

PMID- 24453895
TI  - Impact of sleep respiratory disorders on endothelial function in children.
AB  - Obstructive sleep apnea syndrome (OSAS) in children can induce endothelial
      dysfunction, a well-known early marker of atherosclerosis. The study aimed to
      evaluate a link among endothelial function (measured by flow-mediated
      vasodilation (FMD)), obesity (evaluated by body mass index (BMI)), and sleep
      disordered breathing (SDB), assessed with apnoea/hypopnoea index (AHI), in a
      paediatric population. We demonstrated that our little OSAS patients showed an
      impaired endothelial function as compared to controls. In particular, the higher
      the AHI, the worst the FMD values and thus the endothelial function. Although the
      population sample is small, this study demonstrated that OSAS could impair
      endothelial function and worsen cardiovascular risk profile since childhood. 

PMID- 24453897
TI  - Tensor product model transformation based adaptive integral-sliding mode
      controller: equivalent control method.
AB  - This paper proposes new methodologies for the design of adaptive integral-sliding
      mode control. A tensor product model transformation based adaptive integral
      sliding mode control law with respect to uncertainties and perturbations is
      studied, while upper bounds on the perturbations and uncertainties are assumed to
      be unknown. The advantage of proposed controllers consists in having a dynamical
      adaptive control gain to establish a sliding mode right at the beginning of the
      process. Gain dynamics ensure a reasonable adaptive gain with respect to the
      uncertainties. Finally, efficacy of the proposed controller is verified by
      simulations on an uncertain nonlinear system model. 

PMID- 24453898
TI  - Applying probability theory for the quality assessment of a wildfire spread
      prediction framework based on genetic algorithms.
AB  - This work presents a framework for assessing how the existing constraints at the
      time of attending an ongoing forest fire affect simulation results, both in terms
      of quality (accuracy) obtained and the time needed to make a decision. In the
      wildfire spread simulation and prediction area, it is essential to properly
      exploit the computational power offered by new computing advances. For this
      purpose, we rely on a two-stage prediction process to enhance the quality of
      traditional predictions, taking advantage of parallel computing. This strategy is
      based on an adjustment stage which is carried out by a well-known evolutionary
      technique: Genetic Algorithms. The core of this framework is evaluated according
      to the probability theory principles. Thus, a strong statistical study is
      presented and oriented towards the characterization of such an adjustment
      technique in order to help the operation managers deal with the two aspects
      previously mentioned: time and quality. The experimental work in this paper is
      based on a region in Spain which is one of the most prone to forest fires: El Cap
      de Creus. 

PMID- 24453899
TI  - Influence of image acquisition on radiation dose and image quality: full versus
      narrow phase window acquisition using 320 MDCT.
AB  - PURPOSE: To compare radiation dose and image quality using predefined narrow
      phase window versus complete phase window with dose modulation during R-R using
      320-row MDCTA. METHODS: 114 patients underwent coronary CTA study using 320-row
      MDCT scanner. 87 patients with mean age (61 + 13 years), mean BMI (29 + 6), and
      mean heart rate (HR) (58 + 7 bpm) were imaged at predefined 66-80% R-R interval
      and then reconstructed at 75% while 27 patients with mean age (63 + 16 years),
      mean BMI (28 + 5), and mean HR (57 + 7 bpm) were scanned throughout the complete
      R-R interval with tube current modulation. The effective dose (ED) was calculated
      from dose length product (DLP) and conversion k (0.014 mSv/mGy/cm). Image quality
      was assessed using a three-point ordinal scale (1 = excellent, 2 = good, and 3 =
      nondiagnostic). RESULTS: Both groups were statistically similar to each other
      with reference of HR (P = 0.59), BMI (P = 0.17), and tube current mAs (P = 0.68).
      The median radiation dose was significantly higher in those scanned with complete
      R-R phase window versus narrow phase window (P < 0.0001). Independently of
      patient and scan parameters, increased phase window was associated with higher
      radiation dose (P < 0.001). Image quality was better among those scanned with
      narrow phase window versus complete phase window (P < 0.0001). CONCLUSION: Our
      study supports that good HR control and predefined narrow window acquisition
      result in lower radiation dose without compromising diagnostic image quality for
      coronary disease evaluation.

PMID- 24453900
TI  - An experimental study on pile spacing effects under lateral loading in sand.
AB  - Grouped and single pile behavior differs owing to the impacts of the pile-to-pile
      interaction. Ultimate lateral resistance and lateral subgrade modulus within a
      pile group are known as the key parameters in the soil-pile interaction
      phenomenon. In this study, a series of experimental investigation was carried out
      on single and group pile subjected to monotonic lateral loadings. Experimental
      investigations were conducted on twelve model pile groups of configurations 1 *
      2, 1 * 3, 2 * 2, 3 * 3, and 3 * 2 for embedded length-to-diameter ratio l/d = 32
      into loose and dense sand, spacing from 3 to 6 pile diameter, in parallel and
      series arrangement. The tests were performed in dry sand from Johor Bahru,
      Malaysia. To reconstruct the sand samples, the new designed apparatus, Mobile
      Pluviator, was adopted. The ultimate lateral load is increased 53% in increasing
      of s/d from 3 to 6 owing to effects of sand relative density. An increasing of
      the number of piles in-group decreases the group efficiency owing to the
      increasing of overlapped stress zones and active wedges. A ratio of s/d more than
      6d is large enough to eliminate the pile-to-pile interaction and the group
      effects. It may be more in the loose sand. 

PMID- 24453902
TI  - Evolving MCDM applications using hybrid expert-based ISM and DEMATEL models: an
      example of sustainable ecotourism.
AB  - Ecological degradation is an escalating global threat. Increasingly, people are
      expressing awareness and priority for concerns about environmental problems
      surrounding them. Environmental protection issues are highlighted. An appropriate
      information technology tool, the growing popular social network system (virtual
      community, VC), facilitates public education and engagement with applications for
      existent problems effectively. Particularly, the exploration of related
      involvement behavior of VC member engagement is an interesting topic.
      Nevertheless, member engagement processes comprise interrelated sub-processes
      that reflect an interactive experience within VCs as well as the value co
      creation model. To address the top-focused ecotourism VCs, this study presents an
      application of a hybrid expert-based ISM model and DEMATEL model based on multi
      criteria decision making tools to investigate the complex multidimensional and
      dynamic nature of member engagement. Our research findings provide insightful
      managerial implications and suggest that the viral marketing of ecotourism
      protection is concerned with practitioners and academicians alike. 

PMID- 24453901
TI  - Effectiveness of a theory-driven nutritional education program in improving
      calcium intake among older Mauritian adults.
AB  - Background. Low calcium intake, a risk factor of osteoporosis and subsequent
      fractures, has been previously reported among post-menopausal women in Mauritius.
      Objective. To assess the effectiveness of a theory-based educational intervention
      in improving the calcium intake, self-efficacy, and knowledge of older
      Mauritians. Methodology. The study was conducted as a pre- and post-test design
      which was evaluated through a baseline, immediate postintervention, and 2-month
      follow-up assessments. Participants were adults (n = 189) aged >=40 years old
      from 2 urban community-based centres. The intervention group (IG) (n = 98)
      participated in 6 weekly interactive lessons based on the health belief model
      (HBM). The main outcome measures were calcium intake, HB scale scores, knowledge
      scores, and physical activity level (PAL). Anthropometric measurements were also
      assessed. Results. The IG significantly increased its baseline calcium intake,
      knowledge and self-efficacy (P < 0.001) at post-assessments. A significant
      decrease in waist circumference in the IG was noted (P < 0.05) after
      intervention. PAL significantly increased by 12.3% at post-test and by 29.6% at
      follow-up among intervention adults when compared to the CG (P < 0.001).
      Conclusion. A theory-driven educational intervention is effective in improving
      the dietary calcium intake, knowledge, self-efficacy, and PAL of older community
      based Mauritian adults. 

PMID- 24453903
TI  - Multiple solutions for nonhomogeneous neumann differential inclusion problems by
      the p(x)-Laplacian.
AB  - A class of nonlinear Neumann problems driven by p(x)-Laplacian with a nonsmooth
      locally Lipschitz potential (hemivariational inequality) was considered. The
      approach used in this paper is the variational method for locally Lipschitz
      functions. More precisely, Weierstrass theorem and Mountain Pass theorem are used
      to prove the existence of at least two nontrivial solutions. 

PMID- 24453905
TI  - Power quality control and design of power converter for variable-speed wind
      energy conversion system with permanent-magnet synchronous generator.
AB  - The control strategy and design of an AC/DC/AC IGBT-PMW power converter for PMSG
      based variable-speed wind energy conversion systems (VSWECS) operation in
      grid/load-connected mode are presented. VSWECS consists of a PMSG connected to a
      AC-DC IGBT-based PWM rectifier and a DC/AC IGBT-based PWM inverter with LCL
      filter. In VSWECS, AC/DC/AC power converter is employed to convert the variable
      frequency variable speed generator output to the fixed frequency fixed voltage
      grid. The DC/AC power conversion has been managed out using adaptive neurofuzzy
      controlled inverter located at the output of controlled AC/DC IGBT-based PWM
      rectifier. In this study, the dynamic performance and power quality of the
      proposed power converter connected to the grid/load by output LCL filter is
      focused on. Dynamic modeling and control of the VSWECS with the proposed power
      converter is performed by using MATLAB/Simulink. Simulation results show that the
      output voltage, power, and frequency of VSWECS reach to desirable operation
      values in a very short time. In addition, when PMSG based VSWECS works
      continuously with the 4.5 kHz switching frequency, the THD rate of voltage in the
      load terminal is 0.00672%.

PMID- 24453904
TI  - Association of habitual physical activity measured by an accelerometer with high
      density lipoprotein cholesterol levels in maintenance hemodialysis patients.
AB  - After confirming the relationship between high-density lipoprotein cholesterol
      (HDL-C) levels and mortality in hemodialysis patients for study 1, we
      investigated the effect of physical activity on their HDL-C levels for study 2.
      In study 1, 266 hemodialysis patients were monitored prospectively for five
      years, and Cox proportional hazard regression confirmed the contribution of HDL-C
      to mortality. In study 2, 116 patients were recruited after excluding those with
      severe comorbidities or requiring assistance from another person to walk.
      Baseline characteristics, such as demographic factors, physical constitution,
      primary kidney disease, comorbid conditions, smoking habits, drug use, and
      laboratory parameters, were collected from patient hospital records. An
      accelerometer measured physical activity as the number of steps per day over five
      consecutive days, and multiple regression evaluated the association between
      physical activity and HDL-C levels. Seventy-seven patients died during the follow
      up period. In study 1, we confirmed that HDL-C level was a significant predictor
      of mortality (P = 0.03). After adjusting for patient characteristics in study 2,
      physical activity was independently associated with HDL-C levels (adjusted R (2)
      = 0.255; P = 0.005). In conclusion, physical inactivity was strongly associated
      with decreased HDL-C levels in hemodialysis patients. 

PMID- 24453906
TI  - Diagnostic concordance characteristics of oral cavity lesions.
AB  - PURPOSE: The objective of this study was to evaluate the diagnostic concordance
      characteristics of oral cavity lesions by comparing the clinical diagnosis of the
      lesions with the histopathologic diagnosis. MATERIAL AND METHOD: A retrospective
      analysis was conducted on the patients, who were admitted with oral cavity
      pathology and underwent biopsy procedure between 2007 and 2011. The oral cavity
      lesions were classified into 6 different groups as odontogenic cysts,
      nonodontogenic cysts, odontogenic tumors, nonodontogenic tumors, malignant
      tumors, and precancerous lesions in accordance with the 2005 WHO classification.
      The diagnoses were also recategorized into 3 groups expressing prognostic
      implications as benign, precancerous, and malignant. The initial clinical
      diagnoses were compared with the histopathologic diagnoses. Data were analyzed
      statistically. RESULTS: A total of 2718 cases were included. Histopathologic
      diagnosis did not match the clinical diagnosis in 6.7% of the cases.
      Nonodontogenic tumors and malignant tumors had the highest misdiagnosis rates
      (11.5% and 9%, resp.), followed by odontogenic tumors (7.7%), precancerous
      lesions (6.9%), and odontogenic cysts (4.4%). Clinicians were excelled in
      diagnosis of benign and precancerous lesions in clinical setting. CONCLUSION: The
      detailed discordance characteristics for each specific lesion should be
      considered during oral pathology practice to provide early detection without
      delay.

PMID- 24453907
TI  - In vitro permeation of micronized and nanonized alaptide from semisolid
      formulations.
AB  - This study is focused on in vitro permeation of the original Czech compound, a
      skin/mucosa tissue regeneration promoter, known under the international
      nonproprietary name "alaptide," in micronized and nanonized forms. Alaptide
      showed a great potential for local applications for treatment and/or regeneration
      of the injured skin. The above mentioned technological modifications influence
      the permeation of alaptide through artificial or biological membranes, such as
      PAMPA or skin. The permeation of micronized and nanonized form of alaptide
      formulated to various semisolid pharmaceutical compositions through full
      thickness pig ear skin using a Franz cell has been investigated in detail. In
      general, it can be concluded that the nanonized alaptide permeated through the
      skin less than the micronized form; different observations were made for
      permeation through the PAMPA system, where the micronized form showed lower
      permeation than the nanonized alaptide. 

PMID- 24453908
TI  - A novel method for preparation of Zn-doped CuInS2 solar cells and their
      photovoltaic performance.
AB  - In this study, a novel method was proposed to synthesize high quality Zn-doped
      CuInS2 nanocrystals under high frequency magnetic field at ambient conditions.
      The magnetic Zn-doping gave superparamagnetic heating of the resulting
      nanocrystals via magnetic induction, causing an accelerating growth rate of the
      doped CuInS2 under ambient conditions faster than conventional autoclave
      synthesis. Shape evolution of the Zn-doped CuInS2 nanocrystals from initially
      spherical to pyramidal, to cubic, and finally to a bar geometry was detected as a
      function of time of exposure to magnetic induction. These colloidal solvents with
      different shaped nanocrystals were further used as "nanoink" to fabricate a
      simple thin film solar device; the best efficiency we obtained of these crystals
      was 1.01% with a 1.012 MUm thickness absorber layer (bar geometry). The
      efficiency could be promoted to 1.44% after the absorber was thickened to 2.132
      MUm.

PMID- 24453909
TI  - Seasonal variation of the canopy structure parameters and its correlation with
      yield-related traits in sugarcane.
AB  - Population structure determines sugarcane yield, of which canopy structure is a
      key component. To fully understand the relations between sugarcane yield and
      parameters of the canopy structure, 17 sugarcane varieties were investigated at
      five growth stages. The results indicated that there were significant differences
      between characterized parameters among sugarcane populations at different growth
      stages. During sugarcane growth after planting, leaf area index (LAI) and leaf
      distribution (LD) increased, while transmission coefficient for diffuse radiation
      (TD), mean foliage inclination angle (MFIA), transmission coefficient for solar
      beam radiation penetration (TR), and extinction coefficient (K) decreased.
      Significant negative correlations were found between sugarcane yield and MFIA,
      TD, TR, and K at the early elongation stage, while a significant positive
      correlation between sugarcane yield and LD was found at the same stage. A
      regression for sugarcane yield, with relative error of yield fitting less than
      10%, was successfully established: sugarcane yield = 2380.12 + 46.25 * LD -
      491.82 * LAI + 1.36 * MFIA + 614.91 * TD - 1908.05 * TR - 182.53 * K + 1281.75 *
      LD - 1.35 * MFIA + 831.2 * TR - 407.8 * K + 8.21 * MFIA - 834.50 * TD - 1695.49 *
      K (R (2) = 0.94**).

PMID- 24453910
TI  - New power sharing control for inverter-dominated microgrid based on impedance
      match concept.
AB  - Power flow control is one of the most important issues for operating the inverter
      dominated autonomous microgrid. A technical challenge is how to achieve the
      accurate active/reactive power sharing of inverters. P-F and Q-V droop control
      schemes have been widely used for power sharing in the past decades. But they
      suffer from the poor power sharing in the presence of unequal line impedance. In
      order to solve the problem, a comprehensive analysis of the power droop control
      is presented, and a new droop control based on the impedance match concept is
      proposed in this paper. In addition, the design guidelines of control
      coefficients and virtual impedance are provided. Finally, the performance
      evaluation is carried out, and the evaluation results verify the effectiveness of
      the proposed method. 

PMID- 24453911
TI  - Rumor diffusion in an interests-based dynamic social network.
AB  - To research rumor diffusion in social friend network, based on interests, a
      dynamic friend network is proposed, which has the characteristics of clustering
      and community, and a diffusion model is also proposed. With this friend network
      and rumor diffusion model, based on the zombie-city model, some simulation
      experiments to analyze the characteristics of rumor diffusion in social friend
      networks have been conducted. The results show some interesting observations: (1)
      positive information may evolve to become a rumor through the diffusion process
      that people may modify the information by word of mouth; (2) with the same
      average degree, a random social network has a smaller clustering coefficient and
      is more beneficial for rumor diffusion than the dynamic friend network; (3) a
      rumor is spread more widely in a social network with a smaller global clustering
      coefficient than in a social network with a larger global clustering coefficient;
      and (4) a network with a smaller clustering coefficient has a larger efficiency. 

PMID- 24453912
TI  - Reduction of the livestock ammonia emission under the changing temperature during
      the initial manure nitrogen biomineralization.
AB  - Experimental data were applied for the modelling optimal cowshed temperature
      environment in laboratory test bench by a mass-flow method. The principal factor
      affecting exponent growth of ammonia emission was increasing air and manure
      surface temperature. With the manure temperature increasing from 4 degrees C to
      30 degrees C, growth in the ammonia emission grew fourfold, that is, from 102 to
      430 mg m(-2)h(-1). Especial risk emerges when temperature exceeds 20 degrees C:
      an increase in temperature of 1 degrees C contributes to the intensity of ammonia
      emission by 17 mg m(-2)h(-1). The temperatures of air and manure surface as well
      as those of its layers are important when analysing emission processes from
      manure. Indeed, it affects the processes occurring on the manure surface, namely,
      dehydration and crust formation. To reduce ammonia emission from cowshed, it is
      important to optimize the inner temperature control and to manage air
      circulation, especially at higher temperatures, preventing the warm ambient air
      from blowing direct to manure. Decrease in mean annual temperature of 1 degrees C
      would reduce the annual ammonia emission by some 5.0%. The air temperature range
      varied between -15 degrees C and 30 degrees C in barns. The highest mean annual
      temperature (14.6 degrees C) and ammonia emission (218 mg m(-2)h(-1)) were
      observed in the semideep cowshed.

PMID- 24453914
TI  - An iterative solver in the presence and absence of multiplicity for nonlinear
      equations.
AB  - We develop a high-order fixed point type method to approximate a multiple root.
      By using three functional evaluations per full cycle, a new class of fourth-order
      methods for this purpose is suggested and established. The methods from the class
      require the knowledge of the multiplicity. We also present a method in the
      absence of multiplicity for nonlinear equations. In order to attest the
      efficiency of the obtained methods, we employ numerical comparisons alongside
      obtaining basins of attraction to compare them in the complex plane according to
      their convergence speed and chaotic behavior. 

PMID- 24453913
TI  - Investigation of chemokine receptor CCR2V64Il gene polymorphism and migraine
      without aura in the Iranian population.
AB  - BACKGROUND AND OBJECTIVES: Migraine is a multifactorial common neurovascular
      disease with a polygenic inheritance. Inflammation plays an important part in
      migraine pathophysiology. C-C chemokine receptor 2 (CCR2) is an important
      chemokine for monocyte aggregation and transendothelial monocyte migration. The
      aim of our study was to investigate the association of migraine with CCR2V64Il
      polymorphism in the Iranian population. METHODS: We assessed 103 patients with
      newly diagnosed migraine and 100 healthy subjects. Genomic DNA samples were
      extracted from peripheral blood and genotypes of CCR2V64Il gene polymorphism were
      determined. For measuring the severity of headache, every patient filled out the
      MIGSEV questionnaire. RESULTS: There were no significant differences in the
      distribution of both 64Il allele and heterozygote (GA) genotype of CCR2 gene
      polymorphism (P = 0.396; OR = 0.92, 95% CI = 0.50-1.67 and P = 0.388; OR = 0.91,
      95% CI = 0.47-1.73, resp.) between case and control groups. There was no
      significant difference of alleles frequency between three grades of MIGSEV (P =
      0.922). CONCLUSIONS: In conclusion our results revealed no association between
      CCR2V64Il polymorphism and susceptibility to migraine and also headache severity
      in the Iranian population.

PMID- 24453915
TI  - Application of the denitrification-decomposition model to predict carbon dioxide
      emissions under alternative straw retention methods.
AB  - Straw retention has been shown to reduce carbon dioxide (CO2) emission from
      agricultural soils. But it remains a big challenge for models to effectively
      predict CO2 emission fluxes under different straw retention methods. We used
      maize season data in the Griffith region, Australia, to test whether the
      denitrification-decomposition (DNDC) model could simulate annual CO2 emission. We
      also identified driving factors of CO2 emission by correlation analysis and path
      analysis. We show that the DNDC model was able to simulate CO2 emission under
      alternative straw retention scenarios. The correlation coefficients between
      simulated and observed daily values for treatments of straw burn and straw
      incorporation were 0.74 and 0.82, respectively, in the straw retention period and
      0.72 and 0.83, respectively, in the crop growth period. The results also show
      that simulated values of annual CO2 emission for straw burn and straw
      incorporation were 3.45 t C ha(-1) y(-1) and 2.13 t C ha(-1) y(-1), respectively.
      In addition the DNDC model was found to be more suitable in simulating CO2
      mission fluxes under straw incorporation. Finally the standard multiple
      regression describing the relationship between CO2 emissions and factors found
      that soil mean temperature (SMT), daily mean temperature (T mean), and water
      filled pore space (WFPS) were significant.

PMID- 24453917
TI  - Personality disorders in obsessive-compulsive disorder: a comparative study
      versus other anxiety disorders.
AB  - OBJECTIVE: The purpose of this paper is to provide evidence for the relationship
      between personality disorders (PDs), obsessive compulsive disorder (OCD), and
      other anxiety disorders different from OCD (non-OCD) symptomatology. METHOD: The
      sample consisted of a group of 122 individuals divided into three groups (41 OCD;
      40 non-OCD, and 41 controls) matched by sex, age, and educational level. All the
      individuals answered the IPDE questionnaire and were evaluated by means of the
      SCID-I and SCID-II interviews. RESULTS: Patients with OCD and non-OCD present a
      higher presence of PD. There was an increase in cluster C diagnoses in both
      groups, with no statistically significant differences between them. CONCLUSIONS:
      Presenting anxiety disorder seems to cause a specific vulnerability for PD. Most
      of the PDs that were presented belonged to cluster C. Obsessive Compulsive
      Personality Disorder (OCPD) is the most common among OCD. However, it does not
      occur more frequently among OCD patients than among other anxious patients, which
      does not confirm the continuum between obsessive personality and OCD.
      Implications for categorical and dimensional diagnoses are discussed.

PMID- 24453916
TI  - Correlation between ultrasound reflection intensity and tumor ablation ratio of
      late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on
      ultrasound reflection intensity.
AB  - The minimally invasive high-intensity focused ultrasound (HIFU) therapy is
      thermal ablation treatment for late-stage pancreatic carcinoma with widely
      recognized safety and effectiveness, but there are currently no instant
      assessment methods for its ablation effect. It is vital to find a real-time high
      sensitive assessment method. This research aims to dynamically observe the
      variation rules of ultrasound reflection intensity, analyze the correlation
      between ultrasound reflection intensity and tumor ablation ratio, and find out
      the value of ultrasound reflection intensity in prognosis of HIFU ablation
      effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects
      with late-stage pancreatic carcinoma from March 2007 to December 2009 in the
      study. The variation rules of the ultrasound reflection intensity during HIFU
      therapy were summarized and the correlation between ultrasound reflection
      intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio
      indicated by CT scanning. The conclusion is that variation of ultrasound
      reflection intensity can be used for initial assessment of tumor ablation in HIFU
      therapy and early prognosis of overall HIFU ablation, providing important
      clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound
      can work as a real-time imaging instrument for observation of HIFU ablation
      effect in treating late-stage pancreatic carcinoma. 

PMID- 24453918
TI  - Heteropterys cotinifolia: a neuropharmacological and phytochemical approach with
      possible taxonomic implications.
AB  - Heteropterys cotinifolia (Malpighiaceae) has been used in traditional Mexican
      medicine mainly for the treatment of nervous disorders. However, the specific
      neuropharmacological activities responsible for this use remain to be defined.
      The present study evaluates the antidepressant and anxiolytic effects produced by
      the methanolic extract of Heteropterys cotinifolia and the influence of such
      effects on motor activity in ICR mice. Our results show that the methanolic
      extract of Heteropterys cotinifolia produces a dose-dependent antidepressant
      effect in the forced swimming test in mice at doses from 31 to 310 mg/kg, with no
      reduction of mice locomotion. However, no anxiolytic properties were observed.
      Our findings suggest that the main extract compounds identified as chlorogenic
      acid and rutin may be involved in the antidepressant effects. To our knowledge,
      the present study constitutes the first report of pharmacological and
      phytochemical data of Heteropterys cotinifolia. The presence of flavonoids in the
      methanolic extract of Heteropterys cotinifolia may also provide further data to
      characterize taxonomically this species in order to be distinguished from others
      species closely related and belonging to the same genus.

PMID- 24453919
TI  - Application of response surface methodology for optimizing arginine deiminase
      production medium for Enterococcus faecium sp. GR7.
AB  - Arginine metabolism in Enterococcus faecium sp. GR7 was enhanced via arginine
      deiminase pathway. Process parameters including fermentation media and
      environmental conditions were optimized using independent experiments and
      response surface methodology (central composite design). Fermentation media
      (EAPM) were optimized using independent experiments which resulted in 4-fold
      increase in arginine deiminase specific activity as compared to basal medium. To
      further enhance arginine deiminase activity in E. faecium sp. GR7 and biomass
      production including a five-level central composite design (CCD) was employed to
      study the interactive effect of three-process variables. Response surface
      methodology suggested a quadratic model which was further validated
      experimentally where it showed approximately 15-fold increase in arginine
      metabolism (in terms of arginine deiminase specific activity) over basal medium.
      By solving the regression equation and analyzing the response surface cartons,
      optimal concentrations of the media components (g/L) were determined as arginine
      20.0; tryptone 15.0; lactose 10.0; K2HPO4 3.0; NaCl 1.0, MnSO4 0.6 mM; Tween 80
      1%; pH 6.0 for achieving specific arginine deiminase activity of 4.6 IU/mG with
      concomitant biomass production of 12.1 mg/L. The model is significant as the
      coefficient of determination (R (2)) was 0.87 to 0.90 for all responses. Enhanced
      arginine deiminase yield from E. faecium, a GRAS lactic acid bacterial strain, is
      desirable to explore in vitro therapeutic potential of the arginine metabolizing
      E. faecium sp. GR7.

PMID- 24453920
TI  - A review of refractometric sensors based on long period fibre gratings.
AB  - In the last decade refractometric sensors have attracted an increasing interest
      by the scientific community due to their ability to perform ambient monitoring,
      to assess food quality and safety, and also to the fact that they enable the
      development of label free sensors in the biomedical area. These advances result,
      namely, from the use of long period fibre gratings in the turning points and/or
      with thin films in the transition region that allows resolutions of 10(-6) to
      changes in the refractive index of the surrounding medium. Resolutions exceeding
      10(-8) can also be achieved when long period fibre gratings are combined with
      evanescent field based devices. This paper reviews the recent path towards the
      development of ultrahigh sensitive optical fibre refractometric sensors. 

PMID- 24453921
TI  - Morphological characterization of cherry rootstock candidates selected from
      Central and East Black Sea Regions in Turkey.
AB  - The use of rootstocks particularly for sweet cherry cultivars is of great
      importance for successful and sustainable production. Choosing the right cherry
      rootstocks is just as important as choosing the right cultivar. In this study,
      110 sweet cherry, 30 sour cherry, and 41 mahaleb types displaying rootstock
      potential for sweet cherry cultivars were selected from Central and East Black
      Sea Regions in Turkey. The morphologic characteristics of the studied genotypes
      were compared with the standard clonal rootstocks PHL-A, MaxMa 14, Montmorency,
      Weiroot 158, Gisela 5, Gisela 6, and SL 64. A total of 42 morphological UPOV
      characteristics were evaluated in the selected genotypes and clonal rootstocks.
      The obtained data were analyzed by using principal component analysis and it
      revealed that eigenvalues of the first 3 components were able to represent 36.43%
      of total variance. The most significant positive correlations of the plant vigor
      were determined with leaf blade length and petiole thickness. According to the
      diversity analysis of coefficients, the 05 C 002 and 08 C 039 genotypes were
      identified as being similar (6.66), while the 05 C 002 and 55 S 012 genotypes
      were determined as the most distant genotypes (325.84) in terms of morphology.

PMID- 24453922
TI  - Effect of workplace noise on hearing ability in tile and ceramic industry workers
      in Iran: a 2-year follow-up study.
AB  - INTRODUCTION: Noise as a common physical hazard may lead to noise-induced hearing
      loss, an irreversible but preventable disorder. Annual audiometric evaluations
      help detect changes in hearing status before clinically significant hearing loss
      develops. This study was designed to track hearing threshold changes during 2
      year follow-up among tile and ceramic workers. METHODS: This follow-up study was
      conducted on 555 workers (totally 1110 ears). Subjects were divided into four
      groups according to the level of noise exposure. Hearing threshold in
      conventional audiometric frequencies was measured and standard threshold shift
      was calculated for each ear. RESULTS: Hearing threshold was increased during 2
      years of follow-up. Increased hearing threshold was most frequently observed at
      4000, 6000, and 3000 Hz. Standard threshold shift was observed in 13 (2.34%), 49
      (8.83%), 22 (3.96%), and 63 (11.35%) subjects in the first and second years of
      follow-up in the right and left ears, respectively. CONCLUSIONS: This study has
      documented a high incidence of noise-induced hearing loss in tile and ceramic
      workers that would put stress on the importance of using hearing protection
      devices.

PMID- 24453923
TI  - Online soft sensor of humidity in PEM fuel cell based on dynamic partial least
      squares.
AB  - Online monitoring humidity in the proton exchange membrane (PEM) fuel cell is an
      important issue in maintaining proper membrane humidity. The cost and size of
      existing sensors for monitoring humidity are prohibitive for online measurements.
      Online prediction of humidity using readily available measured data would be
      beneficial to water management. In this paper, a novel soft sensor method based
      on dynamic partial least squares (DPLS) regression is proposed and applied to
      humidity prediction in PEM fuel cell. In order to obtain data of humidity and
      test the feasibility of the proposed DPLS-based soft sensor a hardware-in-the
      loop (HIL) test system is constructed. The time lag of the DPLS-based soft sensor
      is selected as 30 by comparing the root-mean-square error in different time lag.
      The performance of the proposed DPLS-based soft sensor is demonstrated by
      experimental results. 

PMID- 24453925
TI  - Selection of construction methods: a knowledge-based approach.
AB  - The appropriate selection of construction methods to be used during the execution
      of a construction project is a major determinant of high productivity, but
      sometimes this selection process is performed without the care and the systematic
      approach that it deserves, bringing negative consequences. This paper proposes a
      knowledge management approach that will enable the intelligent use of corporate
      experience and information and help to improve the selection of construction
      methods for a project. Then a knowledge-based system to support this decision
      making process is proposed and described. To define and design the system,
      semistructured interviews were conducted within three construction companies with
      the purpose of studying the way that the method' selection process is carried out
      in practice and the knowledge associated with it. A prototype of a Construction
      Methods Knowledge System (CMKS) was developed and then validated with
      construction industry professionals. As a conclusion, the CMKS was perceived as a
      valuable tool for construction methods' selection, by helping companies to
      generate a corporate memory on this issue, reducing the reliance on individual
      knowledge and also the subjectivity of the decision-making process. The described
      benefits as provided by the system favor a better performance of construction
      projects. 

PMID- 24453924
TI  - Reducing agents decrease the oxidative burst and improve clinical outcomes in
      COPD patients: a randomised controlled trial on the effects of sulphurous thermal
      water inhalation.
AB  - BACKGROUND: Inhalation of thermal water with antioxidant properties is
      empirically used for COPD. AIMS: To evaluate the effects of sulphurous thermal
      water (reducing agents) on airway oxidant stress and clinical outcomes in COPD.
      METHODS: Forty moderate-to-severe COPD patients were randomly assigned to receive
      12-day inhalation with sulphurous thermal water or isotonic saline. Patients were
      assessed for superoxide anion (O2 (-)) production in the exhaled breath
      condensate and clinical outcomes at recruitment, the day after the conclusion of
      the 12-day inhalation treatment, and one month after the end of the inhalation
      treatment. RESULTS: Inhalation of reducing agents resulted in a significant
      reduction of O2 (-) production in exhaled breath condensate of COPD patients at
      the end of the inhalatory treatment and at followup compared to baseline. A
      significant improvement in the COPD assessment test (CAT) questionnaire was shown
      one month after the end of the inhalatory treatment only in patients receiving
      sulphurous water. CONCLUSION: Thermal water inhalation produced an in vivo
      antioxidant effect and improvement in health status in COPD patients. Larger
      studies are required in order to evaluate whether inhalation of thermal water is
      able to modify relevant clinical outcomes of the disease (the study was
      registered at clinicaltrial.gov-identifier: NCT01664767).

PMID- 24453926
TI  - A new source of elemol rich essential oil and existence of multicellular oil
      glands in leaves of the Dioscorea species.
AB  - Dioscorea species is a very important food and drug plant. The tubers of the
      plant are extensively used in food and drug purposes owing to the presence of
      steroidal constituent's diosgenin in the tubers. In the present study, we report
      for the first time that the leaves of Dioscorea composita and Dioscorea
      floribunda grown under the field conditions exhibited the presence of
      multicellular oil glands on the epidermal layers of the plants using
      stereomicroscopy (SM) and scanning electron microscopy (SEM). Essential oil was
      also isolated from the otherwise not useful herbage of the plant, and gas
      chromatographic-mass spectroscopy analysis revealed confirmation of the essential
      oil constituents. Out of the 76 compounds detected in D. floribunda and 37 from
      D. composita essential oil, major terpenoids which are detected and reported for
      Dioscorea leaf essential oil are alpha -terpinene, nerolidol, citronellyl
      acetate, farnesol, elemol, alpha -farnesene, valerenyl acetate, and so forth.
      Elemol was detected as the major constituent of both the Dioscorea species
      occupying 41% and 22% of D. Floribunda and D. composita essential oils,
      respectively. In this paper, we report for the first time Dioscorea as a possible
      novel bioresource for the essential oil besides its well-known importance for
      yielding diosgenin. 

PMID- 24453927
TI  - Contrast sensitivity of thyroid associated ophthalmopathy patients without
      obvious optic neuropathy.
AB  - PURPOSE: To compare the contrast sensitivity levels of thyroid associated
      ophthalmopathy (TAO) patients without obvious optic neuropathy with those of
      healthy people. METHODS: Forty eyes of 20 TAO patients without dysthyroid optic
      neuropathy and 40 eyes of 20 healthy subjects were evaluated in this prospective
      case-controlled study. The contrast sensitivity functions (CSFs) of all subjects
      were measured by the functional acuity contrast test (FACT) in five frequencies
      which were 1,5 cpd (A), 3 cpd (B), 6 cpd (C), 12 cpd (D), and 18 cpd (E). Results
      were compared for both groups, and a correlation of CSF with Hertel and clinical
      activity scores was assessed. RESULTS: There was no statistically significant
      difference between TAO patients and control groups for age and sex. TAO patients
      had lower levels than the control group in all the frequencies of CSFs (P < 0.05)
      and the difference in contrast sensitivity functions between the groups seems to
      be more significant in higher frequencies (B, C, D, and E) (P < 0.001).
      CONCLUSIONS: TAO patients without DON can have contrast sensitivity loss and this
      would probably imply subtle optic nerve dysfunction in early disease phase.

PMID- 24453928
TI  - Carbonate chemistry and isotope characteristics of groundwater of Ljubljansko
      polje and Ljubljansko Barje aquifers in Slovenia.
AB  - Ljubljansko polje and Ljubljansko Barje aquifers are the main groundwater
      resources for the needs of Ljubljana, the capital of Slovenia. Carbonate
      chemistry and isotope analysis of the groundwater were performed to acquire new
      hydrogeological data, which should serve as a base for improvement of
      hydrogeological conceptual models of both aquifers. A total of 138 groundwater
      samples were collected at 69 sampling locations from both aquifers. Major
      carbonate ions and the stable isotope of oxygen were used to identify differences
      in the recharging areas of aquifers. Four groups of groundwater were identified:
      (1) Ljubljansko polje aquifer, with higher Ca(2+)values, as limestone
      predominates in its recharge area, (2) northern part of Ljubljansko Barje
      aquifer, with prevailing dolomite in its recharge area, (3) central part of
      Ljubljansko Barje aquifer, which lies below surface cover of impermeable clay and
      is poor in carbonate, and (4) Brest and Iski vrsaj aquifer in the southern part
      of Ljubljansko Barje with higher Mg(2+) in groundwater and dolomite prevailing in
      its recharge area. The radioactive isotope tritium was also used to estimate the
      age of groundwater. Sampled groundwater is recent with tritium activity between 4
      and 8 TU and residence time of up to 10 years. 

PMID- 24453929
TI  - Molecular diagnosis of periprosthetic joint infection by quantitative RT-PCR of
      bacterial 16S ribosomal RNA.
AB  - The diagnosis of periprosthetic joint infection is sometimes straightforward with
      purulent discharge from the fistula tract communicating to the joint prosthesis.
      However it is often difficult to differentiate septic from aseptic loosening of
      prosthesis because of the high culture-negative rates in conventional
      microbiologic culture. This study used quantitative reverse transcription
      polymerase chain reaction (RT-qPCR) to amplify bacterial 16S ribosomal RNA in
      vitro and in 11 clinical samples. The in vitro analysis demonstrated that the RT
      qPCR method was highly sensitive with the detection limit of bacterial 16S rRNA
      being 0.148 pg/ MU l. Clinical specimens were analyzed using the same protocol.
      The RT-qPCR was positive for bacterial detection in 8 culture-positive cases
      (including aerobic, anaerobic, and mycobacteria) and 2 culture-negative cases. It
      was negative in one case that the final diagnosis was confirmed without
      infection. The molecular diagnosis of bacterial infection using RT-qPCR to detect
      bacterial 16S rRNA around a prosthesis correlated well with the clinical
      findings. Based on the promising clinical results, we were attempting to
      differentiate bacterial species or drug-resistant strains by using species
      specific primers and to detect the persistence of bacteria during the interim
      period before the second stage reimplantation in a larger scale of clinical
      subjects.

PMID- 24453930
TI  - The role of epiretinal membrane on treatment of neovascular age-related macular
      degeneration with intravitreal bevacizumab.
AB  - PURPOSE: To determine the effect of epiretinal membranes (ERM) on the treatment
      response and the number of intravitreal bevacizumab injections (IVB) in patients
      with neovascular age-related macular degeneration (nAMD). METHODS: A
      retrospective chart review was performed on 63 eyes of 63 patients. The patients
      were divided into AMD group (n = 35) and AMD/ERM group (n = 28). Best corrected
      visual acuity (BCVA) and central retinal thickness (CRT), as well as the number
      of injections, were evaluated. RESULTS: There was a significant improvement in
      BCVA at 3 months for the AMD and AMD/ERM groups (P = 0.02, P = 0.03, resp.). At
      6, 12, and 18 months, BCVA did not change significantly in either of the groups
      compared to baseline (P > 0.05 for all). At 3, 6, 12, and 24 months, the AMD
      group had an improvement in BCVA (logMAR) of 0.09, 0.06, 0.06, and 0.03 versus
      0.08, 0.07, 0.05, and 0.03 for the AMD/ERM group (P = 0.29, P = 0.88, P = 0.74, P
      = 0.85, resp.). A significant decrease in CRT occurred in both groups for all
      time points (P < 0.001 for all). The change in CRT was not statistically
      different between the two groups at all time points (P > 0.05 for all). The mean
      number of injections over 24 months was 8.8 in the AMD group and 9.2 in the
      AMD/ERM group (P = 0.76). CONCLUSION: During 24 months, visual and anatomical
      outcomes of IVB in nAMD patients were comparable with those in nAMD patients with
      ERM with similar injection numbers.

PMID- 24453931
TI  - Current evidence and insights about genetics in thoracic aorta disease.
AB  - Thoracic aortic aneurysms have been historically considered to be caused by
      etiologic factors similar to those implied in abdominal aortic aneurysms.
      However, during the past decade, there has been increasing evidence that almost
      20% of thoracic aortic aneurysms may be associated with a genetic disease, often
      within a syndromic or familial disorder. Moreover, the presence of congenital
      anomalies, such as bicuspid aortic valve, may have a unique common genetic
      underlying cause. Finally, also sporadic forms have been found to be potentially
      associated with genetic disorders, as highlighted by the analysis of rare
      variants and expression of specific microRNAs. We therefore sought to perform a
      comprehensive review of the role of genetic causes in the development of thoracic
      aortic aneurysms, by analyzing in detail the current evidence of genetic
      alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial
      or sporadic forms, or forms associated with bicuspid aortic valve. 

PMID- 24453932
TI  - Comparison of tubal sterilization procedures performed by keyless abdominal rope
      lifting surgery and conventional CO2 laparoscopy: a case controlled clinical
      study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of Keyless Abdominal Rope-Lifting
      Surgery (KARS), for tubal sterilization procedures in comparison with the
      conventional CO2 laparoscopy. MATERIAL AND METHODS: During a one-year period, 71
      women underwent tubal ligation surgery. Conventional laparoscopy (N = 38) and
      KARS (N = 33) were used for tubal sterilization. In KARS, an abdominal access
      pathway through a single intra-abdominal incision was used to place
      transabdominal sutures that elevated the abdominal wall, and the operations were
      performed through the intraumbilical entry without the use of trocars. In CO2
      laparoscopy, following the creation of the CO2 pneumoperitoneum a 10 mm trocar
      and two 5 mm trocars were introduced into the abdominal cavity. Tubal
      sterilizations were performed following the creation of the abdominal access
      pathways in both groups. The groups were compared with each other. RESULTS: All
      operations could be performed by KARS without conversion to CO2 laparoscopy or
      laparotomy. The mean operative time of the two groups was not significantly
      different (P > 0.05). Intra- and postoperative findings including complications,
      bleeding, and hospital stay time did not differ between groups (P > 0.05).
      CONCLUSION: KARS for tubal sterilization seems safe and effective in terms of
      cosmesis, postoperative pain, and early hospital discharge.

PMID- 24453933
TI  - Hybrid model based on Genetic Algorithms and SVM applied to variable selection
      within fruit juice classification.
AB  - Given the background of the use of Neural Networks in problems of apple juice
      classification, this paper aim at implementing a newly developed method in the
      field of machine learning: the Support Vector Machines (SVM). Therefore, a hybrid
      model that combines genetic algorithms and support vector machines is suggested
      in such a way that, when using SVM as a fitness function of the Genetic Algorithm
      (GA), the most representative variables for a specific classification problem can
      be selected.

PMID- 24453934
TI  - Early symptomatic syndromes eliciting neurodevelopmental clinical examinations.

PMID- 24453935
TI  - Increased Sensitivity of Fluorescence Detection Using Metallic Nanoparticles.
AB  - A new technique called radiative decay engineering can be used to modify
      fluorescence emissions by changing the free space conditions around the
      fluorophores.

PMID- 24453936
TI  - A 26-year-old man with a blind spot in his left eye.

PMID- 24453938
TI  - Revising the economic imperative for US STEM education.
AB  - Over the last decade macroeconomic studies have established a clear link between
      student achievement on science and math tests and per capita gross domestic
      product (GDP) growth, supporting the widely held belief that science, technology,
      engineering, and math(STEM) education are important factors in the production of
      economic prosperity. We critique studies that use science and math tests to
      predict GDP growth, arguing that estimates of the future economic value of STEM
      education involve substantial speculation because they ignore the impacts of
      economic growth on biodiversity and ecosystem functionality, which, in the long
      term, limit the potential for future economic growth. Furthermore, we argue that
      such ecological impacts can be enabled by STEM education. Therefore, we contend
      that the real economic imperative for the STEM pipeline is not just raising
      standardized test scores, but also empowering students to assess, preserve, and
      restore ecosystems in order to reduce ecological degradation and increase
      economic welfare.

PMID- 24453939
TI  - Overcoming the barriers to greater public engagement.

PMID- 24453940
TI  - A20-deficient mast cells exacerbate inflammatory responses in vivo.
AB  - Mast cells are implicated in the pathogenesis of inflammatory and autoimmune
      diseases. However, this notion based on studies in mast cell-deficient mice is
      controversial. We therefore established an in vivo model for hyperactive mast
      cells by specifically ablating the NF-kappaB negative feedback regulator A20.
      While A20 deficiency did not affect mast cell degranulation, it resulted in
      amplified pro-inflammatory responses downstream of IgE/FcepsilonRI, TLRs, IL-1R,
      and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation,
      late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated,
      in contrast to experimental autoimmune encephalomyelitis and immediate
      anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can
      exacerbate inflammatory disorders and define diseases that might benefit from
      therapeutic intervention with mast cell function. 

PMID- 24453941
TI  - The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic
      plasticity.
AB  - Nogo-A is a membrane protein of the central nervous system (CNS) restricting
      neurite growth and synaptic plasticity via two extracellular domains: Nogo-66 and
      Nogo-A-Delta20. Receptors transducing Nogo-A-Delta20 signaling remained elusive
      so far. Here we identify the G protein-coupled receptor (GPCR) sphingosine 1
      phosphate receptor 2 (S1PR2) as a Nogo-A-Delta20-specific receptor. Nogo-A
      Delta20 binds S1PR2 on sites distinct from the pocket of the sphingolipid
      sphingosine 1-phosphate (S1P) and signals via the G protein G13, the Rho GEF
      LARG, and RhoA. Deleting or blocking S1PR2 counteracts Nogo-A-Delta20- and myelin
      mediated inhibition of neurite outgrowth and cell spreading. Blockade of S1PR2
      strongly enhances long-term potentiation (LTP) in the hippocampus of wild-type
      but not Nogo-A(-/-) mice, indicating a repressor function of the Nogo-A/S1PR2
      axis in synaptic plasticity. A similar increase in LTP was also observed in the
      motor cortex after S1PR2 blockade. We propose a novel signaling model in which a
      GPCR functions as a receptor for two structurally unrelated ligands, a membrane
      protein and a sphingolipid. Elucidating Nogo-A/S1PR2 signaling platforms will
      provide new insights into regulation of synaptic plasticity. 

PMID- 24453942
TI  - Different levels of catabolite repression optimize growth in stable and variable
      environments.
AB  - Organisms respond to environmental changes by adapting the expression of key
      genes. However, such transcriptional reprogramming requires time and energy, and
      may also leave the organism ill-adapted when the original environment returns.
      Here, we study the dynamics of transcriptional reprogramming and fitness in the
      model eukaryote Saccharomyces cerevisiae in response to changing carbon
      environments. Population and single-cell analyses reveal that some wild yeast
      strains rapidly and uniformly adapt gene expression and growth to changing carbon
      sources, whereas other strains respond more slowly, resulting in long periods of
      slow growth (the so-called "lag phase") and large differences between individual
      cells within the population. We exploit this natural heterogeneity to evolve a
      set of mutants that demonstrate how the frequency and duration of changes in
      carbon source can favor different carbon catabolite repression strategies. At one
      end of this spectrum are "specialist" strategies that display high rates of
      growth in stable environments, with more stringent catabolite repression and
      slower transcriptional reprogramming. The other mutants display less stringent
      catabolite repression, resulting in leaky expression of genes that are not
      required for growth in glucose. This "generalist" strategy reduces fitness in
      glucose, but allows faster transcriptional reprogramming and shorter lag phases
      when the cells need to shift to alternative carbon sources. Whole-genome
      sequencing of these mutants reveals that mutations in key regulatory genes such
      as HXK2 and STD1 adjust the regulation and transcriptional noise of metabolic
      genes, with some mutations leading to alternative gene regulatory strategies that
      allow "stochastic sensing" of the environment. Together, our study unmasks how
      variable and stable environments favor distinct strategies of transcriptional
      reprogramming and growth. 

PMID- 24453944
TI  - Actin comets: traversing the cellular universe.

PMID- 24453943
TI  - Electron tomography and simulation of baculovirus actin comet tails support a
      tethered filament model of pathogen propulsion.
AB  - Several pathogens induce propulsive actin comet tails in cells they invade to
      disseminate their infection. They achieve this by recruiting factors for actin
      nucleation, the Arp2/3 complex, and polymerization regulators from the host
      cytoplasm. Owing to limited information on the structural organization of actin
      comets and in particular the spatial arrangement of filaments engaged in
      propulsion, the underlying mechanism of pathogen movement is currently
      speculative and controversial. Using electron tomography we have resolved the
      three-dimensional architecture of actin comet tails propelling baculovirus, the
      smallest pathogen yet known to hijack the actin motile machinery. Comet tail
      geometry was also mimicked in mixtures of virus capsids with purified actin and a
      minimal inventory of actin regulators. We demonstrate that propulsion is based on
      the assembly of a fishbone-like array of actin filaments organized in subsets
      linked by branch junctions, with an average of four filaments pushing the virus
      at any one time. Using an energy-minimizing function we have simulated the
      structure of actin comet tails as well as the tracks adopted by baculovirus in
      infected cells in vivo. The results from the simulations rule out gel squeezing
      models of propulsion and support those in which actin filaments are continuously
      tethered during branch nucleation and polymerization. Since Listeria
      monocytogenes, Shigella flexneri, and Vaccinia virus among other pathogens use
      the same common toolbox of components as baculovirus to move, we suggest they
      share the same principles of actin organization and mode of propulsion. 

PMID- 24453945
TI  - Managing incidental genomic findings in clinical trials: fulfillment of the
      principle of justice.

PMID- 24453946
TI  - Cervical screening at age 50-64 years and the risk of cervical cancer at age 65
      years and older: population-based case control study.
AB  - BACKGROUND: There is little consensus, and minimal evidence, regarding the age at
      which to stop cervical screening. We studied the association between screening at
      age 50-64 y and cervical cancer at age 65-83 y. METHODS AND FINDINGS: Cases were
      women (n = 1,341) diagnosed with cervical cancer at age 65-83 y between 1 April
      2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646)
      were randomly selected from population registers. Screening details from 1988
      onwards were extracted from national databases. We calculated the odds ratios
      (OR) for different screening histories and subsequent cervical cancer. Women with
      adequate negative screening at age 65 y (288 cases, 1,395 controls) were at
      lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared
      with those (532 cases, 429 controls) not screened at age 50-64 y (20-y risk: 49
      cancers per 10,000 women, with OR = 0.16, 95% CI 0.13-0.19). ORs depended on the
      age mix of women because of the weakening association with time since last
      screen: OR = 0.11, 95% CI 0.08-0.14 at 2.5 to 7.5 y since last screen; OR = 0.27,
      95% CI 0.20-0.36 at 12.5 to 17.5 y since last screen. Screening at least every
      5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of
      cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21-0.30), and
      the attributable risk was such that in the absence of screening, cervical cancer
      rates in women aged 65+ would have been 2.4 (95% CI 2.1-2.7) times higher. In
      women aged 80-83 y the association was weaker (OR = 0.49, 95% CI 0.28-0.83) than
      in those aged 65-69 y (OR = 0.12, 95% CI 0.09-0.17). This study was limited by an
      absence of data on confounding factors; additionally, findings based on cytology
      may not generalise to human papillomavirus testing. CONCLUSIONS: Women with
      adequate negative screening at age 50-64 y had one-sixth of the risk of cervical
      cancer at age 65-83 y compared with women who were not screened. Stopping
      screening between ages 60 and 69 y in women with adequate negative screening
      seems sensible, but further screening may be justifiable as life expectancy
      increases.

PMID- 24453947
TI  - Cervical cancer screening in older women: new evidence and knowledge gaps.

PMID- 24453948
TI  - Muscle-strengthening and conditioning activities and risk of type 2 diabetes: a
      prospective study in two cohorts of US women.
AB  - BACKGROUND: It is well established that aerobic physical activity can lower the
      risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are
      beneficial for the prevention of T2D is unclear. This study examined the
      association of muscle-strengthening activities with the risk of T2D in women.
      METHODS AND FINDINGS: We prospectively followed up 99,316 middle-aged and older
      women for 8 years from the Nurses' Health Study ([NHS] aged 53-81 years, 2000
      2008) and Nurses' Health Study II ([NHSII] aged 36-55 years, 2001-2009), who were
      free of diabetes, cancer, and cardiovascular diseases at baseline. Participants
      reported weekly time spent on resistance exercise, lower intensity muscular
      conditioning exercises (yoga, stretching, toning), and aerobic moderate and
      vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression
      with adjustment for major determinants for T2D was carried out to examine the
      influence of these types of activities on T2D risk. During 705,869 person years
      of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted
      models including aerobic MVPA, the pooled relative risk (RR) for T2D for women
      performing 1-29, 30-59, 60-150, and >150 min/week of total muscle-strengthening
      and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women
      reporting no muscle-strengthening and conditioning activities (p<0.001 for
      trend). Furthermore, resistance exercise and lower intensity muscular
      conditioning exercises were each independently associated with lower risk of T2D
      in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA
      and at least 60 min/week of muscle-strengthening activities had substantial risk
      reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29-0.38]).
      Limitations to the study include that muscle-strengthening and conditioning
      activity and other types of physical activity were assessed by a self
      administered questionnaire and that the study population consisted of registered
      nurses with mostly European ancestry. CONCLUSIONS: Our study suggests that
      engagement in muscle-strengthening and conditioning activities (resistance
      exercise, yoga, stretching, toning) is associated with a lower risk of T2D.
      Engagement in both aerobic MVPA and muscle-strengthening type activity is
      associated with a substantial reduction in the risk of T2D in middle-aged and
      older women.

PMID- 24453949
TI  - Multidimensional Replica Exchange Molecular Dynamics Yields a Converged Ensemble
      of an RNA Tetranucleotide.
AB  - A necessary step to properly assess and validate the performance of force fields
      for biomolecules is to exhaustively sample the accessible conformational space,
      which is challenging for large RNA structures. Given questions regarding the
      reliability of modeling RNA structure and dynamics with current methods, we have
      begun to use RNA tetranucleotides to evaluate force fields. These systems, though
      small, display considerable conformational variability and complete sampling with
      standard simulation methods remains challenging. Here we compare and discuss the
      performance of known variations of replica exchange molecular dynamics (REMD)
      methods, specifically temperature REMD (T-REMD), Hamiltonian REMD (H-REMD), and
      multidimensional REMD (M-REMD) methods, which have been implemented in Amber's
      accelerated GPU code. Using two independent simulations, we show that M-REMD not
      only makes very efficient use of emerging large-scale GPU clusters, like Blue
      Waters at the University of Illinois, but also is critically important in
      generating the converged ensemble more efficiently than either T-REMD or H-REMD.
      With 57.6 MUs aggregate sampling of a conformational ensemble with M-REMD
      methods, the populations can be compared to NMR data to evaluate force field
      reliability and further understand how putative changes to the force field may
      alter populations to be in more consistent agreement with experiment.

PMID- 24453952
TI  - Machine learning estimates of natural product conformational energies.
AB  - Machine learning has been used for estimation of potential energy surfaces to
      speed up molecular dynamics simulations of small systems. We demonstrate that
      this approach is feasible for significantly larger, structurally complex
      molecules, taking the natural product Archazolid A, a potent inhibitor of
      vacuolar-type ATPase, from the myxobacterium Archangium gephyra as an example.
      Our model estimates energies of new conformations by exploiting information from
      previous calculations via Gaussian process regression. Predictive variance is
      used to assess whether a conformation is in the interpolation region, allowing a
      controlled trade-off between prediction accuracy and computational speed-up. For
      energies of relaxed conformations at the density functional level of theory
      (implicit solvent, DFT/BLYP-disp3/def2-TZVP), mean absolute errors of less than 1
      kcal/mol were achieved. The study demonstrates that predictive machine learning
      models can be developed for structurally complex, pharmaceutically relevant
      compounds, potentially enabling considerable speed-ups in simulations of larger
      molecular structures. 

PMID- 24453953
TI  - Fast reconstruction of compact context-specific metabolic network models.
AB  - Systemic approaches to the study of a biological cell or tissue rely increasingly
      on the use of context-specific metabolic network models. The reconstruction of
      such a model from high-throughput data can routinely involve large numbers of
      tests under different conditions and extensive parameter tuning, which calls for
      fast algorithms. We present fastcore, a generic algorithm for reconstructing
      context-specific metabolic network models from global genome-wide metabolic
      network models such as Recon X. fastcore takes as input a core set of reactions
      that are known to be active in the context of interest (e.g., cell or tissue),
      and it searches for a flux consistent subnetwork of the global network that
      contains all reactions from the core set and a minimal set of additional
      reactions. Our key observation is that a minimal consistent reconstruction can be
      defined via a set of sparse modes of the global network, and fastcore iteratively
      computes such a set via a series of linear programs. Experiments on liver data
      demonstrate speedups of several orders of magnitude, and significantly more
      compact reconstructions, over a rival method. Given its simplicity and its
      excellent performance, fastcore can form the backbone of many future metabolic
      network reconstruction algorithms. 

PMID- 24453954
TI  - PEX5 and ubiquitin dynamics on mammalian peroxisome membranes.
AB  - Peroxisomes are membrane-bound organelles within eukaryotic cells that post
      translationally import folded proteins into their matrix. Matrix protein import
      requires a shuttle receptor protein, usually PEX5, that cycles through docking
      with the peroxisomal membrane, ubiquitination, and export back into the cytosol
      followed by deubiquitination. Matrix proteins associate with PEX5 in the cytosol
      and are translocated into the peroxisome lumen during the PEX5 cycle. This cargo
      translocation step is not well understood, and its energetics remain
      controversial. We use stochastic computational models to explore different ways
      the AAA ATPase driven removal of PEX5 may couple with cargo translocation in
      peroxisomal importers of mammalian cells. The first model considered is
      uncoupled, in which translocation is spontaneous, and does not immediately depend
      on PEX5 removal. The second is directly coupled, in which cargo translocation
      only occurs when its PEX5 is removed from the peroxisomal membrane. The third,
      novel, model is cooperatively coupled and requires two PEX5 on a given importomer
      for cargo translocation--one PEX5 with associated cargo and one with ubiquitin.
      We measure both the PEX5 and the ubiquitin levels on the peroxisomes as we vary
      the matrix protein cargo addition rate into the cytosol. We find that both
      uncoupled and directly coupled translocation behave identically with respect to
      PEX5 and ubiquitin, and the peroxisomal ubiquitin signal increases as the matrix
      protein traffic increases. In contrast, cooperatively coupled translocation
      behaves dramatically differently, with a ubiquitin signal that decreases with
      increasing matrix protein traffic. Recent work has shown that ubiquitin on
      mammalian peroxisome membranes can lead to selective degradation by autophagy, or
      'pexophagy.' Therefore, the high ubiquitin level for low matrix cargo traffic
      with cooperatively coupled protein translocation could be used as a disuse signal
      to mediate pexophagy. This mechanism may be one way that cells could regulate
      peroxisome numbers.

PMID- 24453955
TI  - The correlation structure of local neuronal networks intrinsically results from
      recurrent dynamics.
AB  - Correlated neuronal activity is a natural consequence of network connectivity and
      shared inputs to pairs of neurons, but the task-dependent modulation of
      correlations in relation to behavior also hints at a functional role.
      Correlations influence the gain of postsynaptic neurons, the amount of
      information encoded in the population activity and decoded by readout neurons,
      and synaptic plasticity. Further, it affects the power and spatial reach of
      extracellular signals like the local-field potential. A theory of correlated
      neuronal activity accounting for recurrent connectivity as well as fluctuating
      external sources is currently lacking. In particular, it is unclear how the
      recently found mechanism of active decorrelation by negative feedback on the
      population level affects the network response to externally applied correlated
      stimuli. Here, we present such an extension of the theory of correlations in
      stochastic binary networks. We show that (1) for homogeneous external input, the
      structure of correlations is mainly determined by the local recurrent
      connectivity, (2) homogeneous external inputs provide an additive, unspecific
      contribution to the correlations, (3) inhibitory feedback effectively
      decorrelates neuronal activity, even if neurons receive identical external
      inputs, and (4) identical synaptic input statistics to excitatory and to
      inhibitory cells increases intrinsically generated fluctuations and pairwise
      correlations. We further demonstrate how the accuracy of mean-field predictions
      can be improved by self-consistently including correlations. As a byproduct, we
      show that the cancellation of correlations between the summed inputs to pairs of
      neurons does not originate from the fast tracking of external input, but from the
      suppression of fluctuations on the population level by the local network. This
      suppression is a necessary constraint, but not sufficient to determine the
      structure of correlations; specifically, the structure observed at finite network
      size differs from the prediction based on perfect tracking, even though perfect
      tracking implies suppression of population fluctuations. 

PMID- 24453956
TI  - Phylogenetic Gaussian process model for the inference of functionally important
      regions in protein tertiary structures.
AB  - A critical question in biology is the identification of functionally important
      amino acid sites in proteins. Because functionally important sites are under
      stronger purifying selection, site-specific substitution rates tend to be lower
      than usual at these sites. A large number of phylogenetic models have been
      developed to estimate site-specific substitution rates in proteins and the
      extraordinarily low substitution rates have been used as evidence of function.
      Most of the existing tools, e.g. Rate4Site, assume that site-specific
      substitution rates are independent across sites. However, site-specific
      substitution rates may be strongly correlated in the protein tertiary structure,
      since functionally important sites tend to be clustered together to form
      functional patches. We have developed a new model, GP4Rate, which incorporates
      the Gaussian process model with the standard phylogenetic model to identify
      slowly evolved regions in protein tertiary structures. GP4Rate uses the Gaussian
      process to define a nonparametric prior distribution of site-specific
      substitution rates, which naturally captures the spatial correlation of
      substitution rates. Simulations suggest that GP4Rate can potentially estimate
      site-specific substitution rates with a much higher accuracy than Rate4Site and
      tends to report slowly evolved regions rather than individual sites. In addition,
      GP4Rate can estimate the strength of the spatial correlation of substitution
      rates from the data. By applying GP4Rate to a set of mammalian B7-1 genes, we
      found a highly conserved region which coincides with experimental evidence.
      GP4Rate may be a useful tool for the in silico prediction of functionally
      important regions in the proteins with known structures. 

PMID- 24453957
TI  - Integrated text mining and chemoinformatics analysis associates diet to health
      benefit at molecular level.
AB  - Awareness that disease susceptibility is not only dependent on genetic make up,
      but can be affected by lifestyle decisions, has brought more attention to the
      role of diet. However, food is often treated as a black box, or the focus is
      limited to few, well-studied compounds, such as polyphenols, lipids and
      nutrients. In this work, we applied text mining and Naive Bayes classification to
      assemble the knowledge space of food-phytochemical and food-disease associations,
      where we distinguish between disease prevention/amelioration and disease
      progression. We subsequently searched for frequently occurring phytochemical
      disease pairs and we identified 20,654 phytochemicals from 16,102 plants
      associated to 1,592 human disease phenotypes. We selected colon cancer as a case
      study and analyzed our results in three directions; i) one stop legacy knowledge
      shop for the effect of food on disease, ii) discovery of novel bioactive
      compounds with drug-like properties, and iii) discovery of novel health benefits
      from foods. This works represents a systematized approach to the association of
      food with health effect, and provides the phytochemical layer of information for
      nutritional systems biology research. 

PMID- 24453958
TI  - Microenvironmental variables must influence intrinsic phenotypic parameters of
      cancer stem cells to affect tumourigenicity.
AB  - Since the discovery of tumour initiating cells (TICs) in solid tumours, studies
      focussing on their role in cancer initiation and progression have abounded. The
      biological interrogation of these cells continues to yield volumes of information
      on their pro-tumourigenic behaviour, but actionable generalised conclusions have
      been scarce. Further, new information suggesting a dependence of tumour
      composition and growth on the microenvironment has yet to be studied
      theoretically. To address this point, we created a hybrid, discrete/continuous
      computational cellular automaton model of a generalised stem-cell driven tissue
      with a simple microenvironment. Using the model we explored the phenotypic traits
      inherent to the tumour initiating cells and the effect of the microenvironment on
      tissue growth. We identify the regions in phenotype parameter space where TICs
      are able to cause a disruption in homeostasis, leading to tissue overgrowth and
      tumour maintenance. As our parameters and model are non-specific, they could
      apply to any tissue TIC and do not assume specific genetic mutations. Targeting
      these phenotypic traits could represent a generalizable therapeutic strategy
      across cancer types. Further, we find that the microenvironmental variable does
      not strongly affect the outcomes, suggesting a need for direct feedback from the
      microenvironment onto stem-cell behaviour in future modelling endeavours. 

PMID- 24453959
TI  - Coarse-grained molecular simulation of epidermal growth factor receptor protein
      tyrosine kinase multi-site self-phosphorylation.
AB  - Upon the ligand-dependent dimerization of the epidermal growth factor receptor
      (EGFR), the intrinsic protein tyrosine kinase (PTK) activity of one receptor
      monomer is activated, and the dimeric receptor undergoes self-phosphorylation at
      any of eight candidate phosphorylation sites (P-sites) in either of the two C
      terminal (CT) domains. While the structures of the extracellular ligand binding
      and intracellular PTK domains are known, that of the ~225-amino acid CT domain is
      not, presumably because it is disordered. Receptor phosphorylation on CT domain P
      sites is critical in signaling because of the binding of specific signaling
      effector molecules to individual phosphorylated P-sites. To investigate how the
      combination of conventional substrate recognition and the unique topological
      factors involved in the CT domain self-phosphorylation reaction lead to
      selectivity in P-site phosphorylation, we performed coarse-grained molecular
      simulations of the P-site/catalytic site binding reactions that precede EGFR self
      phosphorylation events. Our results indicate that self-phosphorylation of the
      dimeric EGFR, although generally believed to occur in trans, may well occur with
      a similar efficiency in cis, with the P-sites of both receptor monomers being
      phosphorylated to a similar extent. An exception was the case of the most kinase
      proximal P-site-992, the catalytic site binding of which occurred exclusively in
      cis via an intramolecular reaction. We discovered that the in cis interaction of
      P-site-992 with the catalytic site was facilitated by a cleft between the N
      terminal and C-terminal lobes of the PTK domain that allows the short CT domain
      sequence tethering P-site-992 to the PTK core to reach the catalytic site. Our
      work provides several new mechanistic insights into the EGFR self-phosphorylation
      reaction, and demonstrates the potential of coarse-grained molecular simulation
      approaches for investigating the complexities of self-phosphorylation in
      molecules such as EGFR (HER/ErbB) family receptors and growth factor receptor
      PTKs in general. 

PMID- 24453960
TI  - The making of the Women in Biology forum (WiB) at Bioclues.
AB  - The Women in Biology forum (WiB) of Bioclues (India) began in 2009 to promote and
      support women pursuing careers in bioinformatics and computational biology. WiB
      was formed in order to help women scientists deprived of basic research, boost
      the prominence of women scientists particularly from developing countries, and
      bridge the gender gap to innovation. WiB has also served as a platform to
      highlight the work of established female scientists in these fields. Several
      award-winning women researchers have shared their experiences and provided
      valuable suggestions to WiB. Headed by Mohanalatha Chandrasekharan and supported
      by Dr. Reeta Rani Singhania and Renuka Suravajhala, WiB has seen major progress
      in the last couple of years particularly in the two avenues Mentoring and
      Research, off the four avenues in Bioclues: Mentoring, Outreach, Research and
      Entrepreneurship (MORE). In line with the Bioclues vision for bioinformatics in
      India, the WiB Journal Club (JoC) recognizes women scientists working on
      functional genomics and bioinformatics, and provides scientific mentorship and
      support for project design and hypothesis formulation. As a part of Bioclues, WiB
      members practice the group's open-desk policy and its belief that all members are
      free to express their own thoughts and opinions. The WiB forum appreciates
      suggestions and welcomes scientists from around the world to be a part of their
      mission to encourage women to pursue computational biology and bioinformatics. 

PMID- 24453961
TI  - PredictSNP: robust and accurate consensus classifier for prediction of disease
      related mutations.
AB  - Single nucleotide variants represent a prevalent form of genetic variation.
      Mutations in the coding regions are frequently associated with the development of
      various genetic diseases. Computational tools for the prediction of the effects
      of mutations on protein function are very important for analysis of single
      nucleotide variants and their prioritization for experimental characterization.
      Many computational tools are already widely employed for this purpose.
      Unfortunately, their comparison and further improvement is hindered by large
      overlaps between the training datasets and benchmark datasets, which lead to
      biased and overly optimistic reported performances. In this study, we have
      constructed three independent datasets by removing all duplicities,
      inconsistencies and mutations previously used in the training of evaluated tools.
      The benchmark dataset containing over 43,000 mutations was employed for the
      unbiased evaluation of eight established prediction tools: MAPP, nsSNPAnalyzer,
      PANTHER, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT and SNAP. The six best performing
      tools were combined into a consensus classifier PredictSNP, resulting into
      significantly improved prediction performance, and at the same time returned
      results for all mutations, confirming that consensus prediction represents an
      accurate and robust alternative to the predictions delivered by individual tools.
      A user-friendly web interface enables easy access to all eight prediction tools,
      the consensus classifier PredictSNP and annotations from the Protein Mutant
      Database and the UniProt database. The web server and the datasets are freely
      available to the academic community at http://loschmidt.chemi.muni.cz/predictsnp.

PMID- 24453963
TI  - From scourge to cure: tumour-selective viral pathogenesis as a new strategy
      against cancer.
AB  - Tumour mutations corrupt cellular pathways, and accumulate to disrupt,
      dysregulate, and ultimately avoid mechanisms of cellular control. Yet the very
      changes that tumour cells undergo to secure their own growth success also render
      them susceptible to viral infection. Enhanced availability of surface receptors,
      disruption of antiviral sensing, elevated metabolic activity, disengagement of
      cell cycle controls, hyperactivation of mitogenic pathways, and apoptotic
      avoidance all render the malignant cell environment highly supportive to viral
      replication. The therapeutic use of oncolytic viruses (OVs) with a natural
      tropism for infecting and subsequently lysing tumour cells is a rapidly
      progressing area of cancer research. While many OVs exhibit an inherent degree of
      tropism for transformed cells, this can be further promoted through
      pharmacological interventions and/or the introduction of viral mutations that
      generate recombinant oncolytic viruses adapted to successfully replicate only in
      a malignant cellular environment. Such adaptations that augment OV tumour
      selectivity are already improving the therapeutic outlook for cancer, and there
      remains tremendous untapped potential for further innovation. 

PMID- 24453965
TI  - Ranaviruses: not just for frogs.

PMID- 24453964
TI  - KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated
      herpesvirus genome using next-generation sequencing reveals novel genomic and
      functional features.
AB  - Productive herpesvirus infection requires a profound, time-controlled remodeling
      of the viral transcriptome and proteome. To gain insights into the genomic
      architecture and gene expression control in Kaposi's sarcoma-associated
      herpesvirus (KSHV), we performed a systematic genome-wide survey of viral
      transcriptional and translational activity throughout the lytic cycle. Using mRNA
      sequencing and ribosome profiling, we found that transcripts encoding lytic genes
      are promptly bound by ribosomes upon lytic reactivation, suggesting their
      regulation is mainly transcriptional. Our approach also uncovered new genomic
      features such as ribosome occupancy of viral non-coding RNAs, numerous upstream
      and small open reading frames (ORFs), and unusual strategies to expand the virus
      coding repertoire that include alternative splicing, dynamic viral mRNA editing,
      and the use of alternative translation initiation codons. Furthermore, we provide
      a refined and expanded annotation of transcription start sites, polyadenylation
      sites, splice junctions, and initiation/termination codons of known and new viral
      features in the KSHV genomic space which we have termed KSHV 2.0. Our results
      represent a comprehensive genome-scale image of gene regulation during lytic KSHV
      infection that substantially expands our understanding of the genomic
      architecture and coding capacity of the virus. 

PMID- 24453966
TI  - Single cell stochastic regulation of pilus phase variation by an attenuation-like
      mechanism.
AB  - The molecular triggers leading to virulence of a number of human-adapted
      commensal bacteria such as Streptococcus gallolyticus are largely unknown. This
      opportunistic pathogen is responsible for endocarditis in the elderly and
      associated with colorectal cancer. Colonization of damaged host tissues with
      exposed collagen, such as cardiac valves and pre-cancerous polyps, is mediated by
      appendages referred to as Pil1 pili. Populations of S. gallolyticus are
      heterogeneous with the majority of cells weakly piliated while a smaller fraction
      is hyper piliated. We provide genetic evidences that heterogeneous pil1
      expression depends on a phase variation mechanism involving addition/deletion of
      GCAGA repeats that modifies the length of an upstream leader peptide. Synthesis
      of longer leader peptides potentiates the transcription of the pil1 genes through
      ribosome-induced destabilization of a premature stem-loop transcription
      terminator. This study describes, at the molecular level, a new regulatory
      mechanism combining phase variation in a leader peptide-encoding gene and
      transcription attenuation. This simple and robust mechanism controls a stochastic
      heterogeneous pilus expression, which is important for evading the host immune
      system while ensuring optimal tissue colonization. 

PMID- 24453967
TI  - Nutrient limitation governs Staphylococcus aureus metabolism and niche adaptation
      in the human nose.
AB  - Colonization of the human nose by Staphylococcus aureus in one-third of the
      population represents a major risk factor for invasive infections. The basis for
      adaptation of S. aureus to this specific habitat and reasons for the human
      predisposition to become colonized have remained largely unknown. Human nasal
      secretions were analyzed by metabolomics and found to contain potential nutrients
      in rather low amounts. No significant differences were found between S. aureus
      carriers and non-carriers, indicating that carriage is not associated with
      individual differences in nutrient supply. A synthetic nasal medium (SNM3) was
      composed based on the metabolomics data that permits consistent growth of S.
      aureus isolates. Key genes were expressed in SNM3 in a similar way as in the
      human nose, indicating that SNM3 represents a suitable surrogate environment for
      in vitro simulation studies. While the majority of S. aureus strains grew well in
      SNM3, most of the tested coagulase-negative staphylococci (CoNS) had major
      problems to multiply in SNM3 supporting the notion that CoNS are less well
      adapted to the nose and colonize preferentially the human skin. Global gene
      expression analysis revealed that, during growth in SNM3, S. aureus depends
      heavily on de novo synthesis of methionine. Accordingly, the methionine
      biosynthesis enzyme cysteine-gamma-synthase (MetI) was indispensable for growth
      in SNM3, and the MetI inhibitor DL-propargylglycine inhibited S. aureus growth in
      SNM3 but not in the presence of methionine. Of note, metI was strongly up
      regulated by S. aureus in human noses, and metI mutants were strongly abrogated
      in their capacity to colonize the noses of cotton rats. These findings indicate
      that the methionine biosynthetic pathway may include promising antimicrobial
      targets that have previously remained unrecognized. Hence, exploring the
      environmental conditions facultative pathogens are exposed to during colonization
      can be useful for understanding niche adaptation and identifying targets for new
      antimicrobial strategies. 

PMID- 24453968
TI  - Kaposi's sarcoma associated herpesvirus tegument protein ORF75 is essential for
      viral lytic replication and plays a critical role in the antagonization of ND10
      instituted intrinsic immunity.
AB  - Nuclear domain 10 (ND10) components are restriction factors that inhibit
      herpesviral replication. Effector proteins of different herpesviruses can
      antagonize this restriction by a variety of strategies, including degradation or
      relocalization of ND10 proteins. We investigated the interplay of Kaposi's
      Sarcoma-Associated Herpesvirus (KSHV) infection and cellular defense by nuclear
      domain 10 (ND10) components. Knock-down experiments in primary human cells show
      that KSHV-infection is restricted by the ND10 components PML and Sp100, but not
      by ATRX. After KSHV infection, ATRX is efficiently depleted and Daxx is dispersed
      from ND10, indicating that these two ND10 components can be antagonized by KSHV.
      We then identified the ORF75 tegument protein of KSHV as the viral factor that
      induces the disappearance of ATRX and relocalization of Daxx. ORF75 belongs to a
      viral protein family (viral FGARATs) that has homologous proteins in all gamma
      herpesviruses. Isolated expression of ORF75 in primary cells induces a
      relocalization of PML and dispersal of Sp100, indicating that this viral effector
      protein is able to influence multiple ND10 components. Moreover, by constructing
      a KSHV mutant harboring a stop codon at the beginning of ORF75, we could
      demonstrate that ORF75 is absolutely essential for viral replication and the
      initiation of viral immediate-early gene expression. Using recombinant viruses
      either carrying Flag- or YFP-tagged variants of ORF75, we could further
      corroborate the role of ORF75 in the antagonization of ND10-mediated intrinsic
      immunity, and show that it is independent of the PML antagonist vIRF3. Members of
      the viral FGARAT family target different ND10 components, suggesting that the
      ND10 targets of viral FGARAT proteins have diversified during evolution. We
      assume that overcoming ND10 intrinsic defense constitutes a critical event in the
      replication of all herpesviruses; on the other hand, restriction of herpesviral
      replication by ND10 components may also promote latency as the default outcome of
      infection. 

PMID- 24453969
TI  - HIV protective KIR3DL1/S1-HLA-B genotypes influence NK cell-mediated inhibition
      of HIV replication in autologous CD4 targets.
AB  - Carriage of the genetic combination encoding a high expression inhibitory Killer
      Immunoglobulin-like Receptor (KIR)3DL1 with its ligand, HLA-B*57 (*h/*y+B*57) is
      associated with slower time to AIDS and better HIV viral load control than being
      a Bw6 homozygote (Bw6hmz). Natural Killer (NK) cells from *h/*y+B*57 carriers
      receive potent educational signals through HLA-B*57 KIR3DL1 ligation leading to
      high functional potential. NK cells from Bw6hmz are not educated through KIR3DL1
      because Bw6 antigens do not interact with this inhibitory receptor. To better
      understand the impact of KIR/HLA combinations on NK cell mediated anti-viral
      activity we measured NK cell mediated inhibition of HIV replication in autologous
      infected CD4 (iCD4) cells by assessing the frequency of p24 positive CD4 targets
      and supernatant levels of HIV p24 longitudinally in the presence versus absence
      of NK cells. Forty-seven HIV uninfected subjects were studied, including carriers
      of *h/*y+B*57, a low expression KIR3DL1 genotype with HLA-B*57 termed *l/*x+B*57,
      a genotype designated 3DS1+*80I and Bw6hmz. NK cells from *h/*y+B*57 carriers,
      like those from 3DS1+*80I subjects, inhibited HIV replication in autologous iCD4
      cells better than those from Bw6hmz and *l/*x+B*57 carriers. Cell contact between
      NK and iCD4 cells activated NK cells to inhibit viral replication in a non
      contact dependent fashion through secretion of CC-chemokines. iCD4 stimulated NK
      cells from *h/*y+B*57 and 3DS1+*80I carriers produced higher levels of CC
      chemokines than those from Bw6hmz or *l/*x+B*57 carriers. Higher levels of CC
      chemokines were produced by KIR3DL1(+) than KIR3DL1(-) NK cells. We conclude that
      NK-mediated inhibition of viral replication in autologous iCD4 cells is partially
      due to a block at the level of HIV entry into new targets by secreted CC
      chemokines. 

PMID- 24453970
TI  - Phosphoenolpyruvate carboxylase identified as a key enzyme in erythrocytic
      Plasmodium falciparum carbon metabolism.
AB  - Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in the
      Plasmodium falciparum genome, suggesting that PEPC has a parasite-specific
      function. To investigate its importance in P. falciparum, we generated a pepc
      null mutant (D10(Deltapepc) ), which was only achievable when malate, a reduction
      product of oxaloacetate, was added to the growth medium. D10(Deltapepc) had a
      severe growth defect in vitro, which was partially reversed by addition of malate
      or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics
      using (13)C-U-D-glucose and (13)C-bicarbonate showed that the conversion of
      glycolytically-derived PEP into malate, fumarate, aspartate and citrate was
      abolished in D10(Deltapepc) and that pentose phosphate pathway metabolites and
      glycerol 3-phosphate were present at increased levels. In contrast, metabolism of
      the carbon skeleton of (13)C,(15)N-U-glutamine was similar in both parasite
      lines, although the flux was lower in D10(Deltapepc); it also confirmed the
      operation of a complete forward TCA cycle in the wild type parasite. Overall,
      these data confirm the CO2 fixing activity of PEPC and suggest that it provides
      metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic
      and mitochondrial redox balance. Moreover, these findings imply that PEPC may be
      an exploitable target for future drug discovery.

PMID- 24453971
TI  - Alphavirus mutator variants present host-specific defects and attenuation in
      mammalian and insect models.
AB  - Arboviruses cycle through both vertebrates and invertebrates, which requires them
      to adapt to disparate hosts while maintaining genetic integrity during genome
      replication. To study the genetic mechanisms and determinants of these processes,
      we use chikungunya virus (CHIKV), a re-emerging human pathogen transmitted by the
      Aedes mosquito. We previously isolated a high fidelity (or antimutator)
      polymerase variant, C483Y, which had decreased fitness in both mammalian and
      mosquito hosts, suggesting this residue may be a key molecular determinant. To
      further investigate effects of position 483 on RNA-dependent RNA-polymerase
      (RdRp) fidelity, we substituted every amino acid at this position. We isolated
      novel mutators with decreased replication fidelity and higher mutation
      frequencies, allowing us to examine the fitness of error-prone arbovirus
      variants. Although CHIKV mutators displayed no major replication defects in
      mammalian cell culture, they had reduced specific infectivity and were attenuated
      in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and
      the variants exhibited significant defects in RNA synthesis. Consequently, these
      replication defects resulted in strong selection for reversion during infection
      of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the
      analogous mutations in Sindbis virus (SINV), which also reduced polymerase
      fidelity and generated replication defects in mosquito cells. However,
      replication defects were mosquito cell-specific and were not observed in
      Drosophila S2 cells, allowing us to evaluate the potential attenuation of
      mutators in insect models where pressure for reversion was absent. Indeed, the
      SINV mutator variant was attenuated in fruit flies. These findings confirm that
      residue 483 is a determinant regulating alphavirus polymerase fidelity and
      demonstrate proof of principle that arboviruses can be attenuated in mammalian
      and insect hosts by reducing fidelity. 

PMID- 24453972
TI  - Serotonin signaling in Schistosoma mansoni: a serotonin-activated G protein
      coupled receptor controls parasite movement.
AB  - Serotonin is an important neuroactive substance in all the parasitic helminths.
      In Schistosoma mansoni, serotonin is strongly myoexcitatory; it potentiates
      contraction of the body wall muscles and stimulates motor activity. This is
      considered to be a critical mechanism of motor control in the parasite, but the
      mode of action of serotonin is poorly understood. Here we provide the first
      molecular evidence of a functional serotonin receptor (Sm5HTR) in S. mansoni. The
      schistosome receptor belongs to the G protein-coupled receptor (GPCR) superfamily
      and is distantly related to serotonergic type 7 (5HT7) receptors from other
      species. Functional expression studies in transfected HEK 293 cells showed that
      Sm5HTR is a specific serotonin receptor and it signals through an increase in
      intracellular cAMP, consistent with a 5HT7 signaling mechanism.
      Immunolocalization studies with a specific anti-Sm5HTR antibody revealed that the
      receptor is abundantly distributed in the worm's nervous system, including the
      cerebral ganglia and main nerve cords of the central nervous system and the
      peripheral innervation of the body wall muscles and tegument. RNA interference
      (RNAi) was performed both in schistosomulae and adult worms to test whether the
      receptor is required for parasite motility. The RNAi-suppressed adults and larvae
      were markedly hypoactive compared to the corresponding controls and they were
      also resistant to exogenous serotonin treatment. These results show that Sm5HTR
      is at least one of the receptors responsible for the motor effects of serotonin
      in S. mansoni. The fact that Sm5HTR is expressed in nerve tissue further suggests
      that serotonin stimulates movement via this receptor by modulating neuronal
      output to the musculature. Together, the evidence identifies Sm5HTR as an
      important neuronal protein and a key component of the motor control apparatus in
      S. mansoni. 

PMID- 24453973
TI  - A substrate-fusion protein is trapped inside the Type III Secretion System
      channel in Shigella flexneri.
AB  - The Type III Secretion System (T3SS) is a macromolecular complex used by Gram
      negative bacteria to secrete effector proteins from the cytoplasm across the
      bacterial envelope in a single step. For many pathogens, the T3SS is an essential
      virulence factor that enables the bacteria to interact with and manipulate their
      respective host. A characteristic structural feature of the T3SS is the needle
      complex (NC). The NC resembles a syringe with a basal body spanning both
      bacterial membranes and a long needle-like structure that protrudes from the
      bacterium. Based on the paradigm of a syringe-like mechanism, it is generally
      assumed that effectors and translocators are unfolded and secreted from the
      bacterial cytoplasm through the basal body and needle channel. Despite extensive
      research on T3SS, this hypothesis lacks experimental evidence and the mechanism
      of secretion is not fully understood. In order to elucidate details of the T3SS
      secretion mechanism, we generated fusion proteins consisting of a T3SS substrate
      and a bulky protein containing a knotted motif. Because the knot cannot be
      unfolded, these fusions are accepted as T3SS substrates but remain inside the NC
      channel and obstruct the T3SS. To our knowledge, this is the first time substrate
      fusions have been visualized together with isolated NCs and we demonstrate that
      substrate proteins are secreted directly through the channel with their N
      terminus first. The channel physically encloses the fusion protein and shields it
      from a protease and chemical modifications. Our results corroborate an elementary
      understanding of how the T3SS works and provide a powerful tool for in situ
      structural investigations in the future. This approach might also be applicable
      to other protein secretion systems that require unfolding of their substrates
      prior to secretion. 

PMID- 24453974
TI  - Gammaherpesviral gene expression and virion composition are broadly controlled by
      accelerated mRNA degradation.
AB  - Lytic gammaherpesvirus infection restricts host gene expression by promoting
      widespread degradation of cytoplasmic mRNA through the activity of the viral
      endonuclease SOX. Though generally assumed to be selective for cellular
      transcripts, the extent to which SOX impacts viral mRNA stability has remained
      unknown. We addressed this issue using the model murine gammaherpesvirus MHV68
      and, unexpectedly, found that all stages of viral gene expression are controlled
      through mRNA degradation. Using both comprehensive RNA expression profiling and
      half-life studies we reveal that the levels of the majority of viral mRNAs but
      not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of
      viral mRNA by muSOX is functionally significant, as it impacts intracellular
      viral protein abundance and progeny virion composition. In the absence of muSOX
      imposed gene expression control the viral particles display increased cell
      surface binding and entry as well as enhanced immediate early gene expression.
      These phenotypes culminate in a viral replication defect in multiple cell types
      as well as in vivo, highlighting the importance of maintaining the appropriate
      balance of viral RNA during gammaherpesviral infection. This is the first example
      of a virus that fails to broadly discriminate between cellular and viral
      transcripts during host shutoff and instead uses the targeting of viral messages
      to fine-tune overall gene expression. 

PMID- 24453975
TI  - The Arabidopsis miR472-RDR6 silencing pathway modulates PAMP- and effector
      triggered immunity through the post-transcriptional control of disease resistance
      genes.
AB  - RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) is a key RNA silencing factor initially
      characterized in transgene silencing and virus resistance. This enzyme also
      contributes to the biosynthesis of endogenous short interfering RNAs (siRNAs)
      from non-coding RNAs, transposable elements and protein-coding transcripts. One
      class of protein-coding transcripts that have recently emerged as major sources
      of RDR6-dependent siRNAs are nucleotide-binding leucine-rich repeat (NB-LRR)
      proteins, a family of immune-receptors that perceive specific pathogen effector
      proteins and mount Effector-Triggered Immunity (ETI). Nevertheless, the dynamic
      post-transcriptional control of NB-LRR transcripts during the plant immune
      response and the functional relevance of NB-LRRs in signaling events triggered by
      Pathogen-Associated Molecular Patterns (PAMPs) remain elusive. Here, we show that
      PTI is constitutive and sensitized in the Arabidopsis rdr6 loss-of-function
      mutant, implicating RDR6 as a novel negative regulator of PTI. Accordingly, rdr6
      mutant exhibits enhanced basal resistance towards a virulent Pseudomonas syringae
      strain. We further provide evidence that dozens of CC-NB-LRRs (CNLs), including
      the functionally characterized RPS5 gene, are post-transcriptionally controlled
      by RDR6 both constitutively and during PTI. These CNL transcripts are also
      regulated by the Arabidopsis microRNA miR472 and knock-down of this miRNA
      recapitulates the PTI and basal resistance phenotypes observed in the rdr6 mutant
      background. Furthermore, both miR472 and rdr6 mutants were more resistant to Pto
      DC3000 expressing AvrPphB, a bacterial effector recognized by the disease
      resistance protein RPS5, whereas transgenic plants overexpressing miR472 were
      more susceptible to this bacterial strain. Finally, we show that the enhanced
      basal and RPS5-mediated resistance phenotypes observed in the rdr6 mutant are
      dependent on the proper chaperoning of NB-LRR proteins, and might therefore be
      due to the enhanced accumulation of CNL proteins whose cognate mRNAs are no
      longer controlled by RDR6-dependent siRNAs. Altogether, this study supports a
      model whereby the miR472- and RDR6-mediated silencing pathway represents a key
      regulatory checkpoint modulating both PTI and ETI responses through the post
      transcriptional control of disease resistance genes. 

PMID- 24453976
TI  - Lu/BCAM adhesion glycoprotein is a receptor for Escherichia coli Cytotoxic
      Necrotizing Factor 1 (CNF1).
AB  - The Cytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin which is a major
      virulence factor of pathogenic Escherichia coli strains. Here, we identified the
      Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) as
      cellular receptor for CNF1 by co-precipitation of cell surface molecules with
      tagged toxin. The CNF1-Lu/BCAM interaction was verified by direct protein-protein
      interaction analysis and competition studies. These studies revealed amino acids
      720 to 1014 of CNF1 as the binding site for Lu/BCAM. We suggest two cell
      interaction sites in CNF1: first the N-terminus, which binds to p37LRP as
      postulated before. Binding of CNF1 to p37LRP seems to be crucial for the toxin's
      action. However, it is not sufficient for the binding of CNF1 to the cell
      surface. A region directly adjacent to the catalytic domain is a high affinity
      interaction site for Lu/BCAM. We found Lu/BCAM to be essential for the binding of
      CNF1 to cells. Cells deficient in Lu/BCAM but expressing p37LRP could not bind
      labeled CNF1. Therefore, we conclude that LRP and Lu/BCAM are both required for
      toxin action but with different functions. 

PMID- 24453977
TI  - Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation
      and hypersensitivity to bacterial superinfection.
AB  - Cyclic paroxysm and high fever are hallmarks of malaria and are associated with
      high levels of pyrogenic cytokines, including IL-1beta. In this report, we
      describe a signature for the expression of inflammasome-related genes and caspase
      1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was
      sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma
      priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or
      NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was
      also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of
      Plasmodium-induced caspase-1 activation, mice produced extremely high levels of
      IL-1beta upon a second microbial stimulus, and became hypersensitive to septic
      shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial
      induced lethality in rodents. Similar to mice, we observed a significantly
      increased frequency of circulating CD14(+)CD16(-)Caspase-1(+) and
      CD14(dim)CD16(+)Caspase-1(+) monocytes in peripheral blood mononuclear cells from
      febrile malaria patients. These cells readily produced large amounts of IL-1beta
      after stimulation with LPS. Furthermore, we observed the presence of inflammasome
      complexes in monocytes from malaria patients containing either NLRP3 or NLRP12
      pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is
      likely to be a key event in mediating systemic production of IL-1beta and
      hypersensitivity to secondary bacterial infection during malaria. 

PMID- 24453978
TI  - Regulators of Trypanosoma brucei cell cycle progression and differentiation
      identified using a kinome-wide RNAi screen.
AB  - The African trypanosome, Trypanosoma brucei, maintains an integral link between
      cell cycle regulation and differentiation during its intricate life cycle. Whilst
      extensive changes in phosphorylation have been documented between the mammalian
      bloodstream form and the insect procyclic form, relatively little is known about
      the parasite's protein kinases (PKs) involved in the control of cellular
      proliferation and differentiation. To address this, a T. brucei kinome-wide RNAi
      cell line library was generated, allowing independent inducible knockdown of each
      of the parasite's 190 predicted protein kinases. Screening of this library using
      a cell viability assay identified >=42 PKs that are required for normal
      bloodstream form proliferation in culture. A secondary screen identified 24 PKs
      whose RNAi-mediated depletion resulted in a variety of cell cycle defects
      including in G1/S, kinetoplast replication/segregation, mitosis and cytokinesis,
      15 of which are novel cell cycle regulators. A further screen identified for the
      first time two PKs, named repressor of differentiation kinase (RDK1 and RDK2),
      depletion of which promoted bloodstream to procyclic form differentiation. RDK1
      is a membrane-associated STE11-like PK, whilst RDK2 is a NEK PK that is essential
      for parasite proliferation. RDK1 acts in conjunction with the PTP1/PIP39
      phosphatase cascade to block uncontrolled bloodstream to procyclic form
      differentiation, whilst RDK2 is a PK whose depletion efficiently induces
      differentiation in the absence of known triggers. Thus, the RNAi kinome library
      provides a valuable asset for functional analysis of cell signalling pathways in
      African trypanosomes as well as drug target identification and validation. 

PMID- 24453979
TI  - Glutamate utilization couples oxidative stress defense and the tricarboxylic acid
      cycle in Francisella phagosomal escape.
AB  - Intracellular bacterial pathogens have developed a variety of strategies to avoid
      degradation by the host innate immune defense mechanisms triggered upon
      phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen
      Francisella replicates exclusively in the cytosolic compartment. Hence, its
      ability to escape rapidly from the phagosomal compartment is critical for its
      pathogenicity. Here, we show for the first time that a glutamate transporter of
      Francisella (here designated GadC) is critical for oxidative stress defense in
      the phagosome, thus impairing intra-macrophage multiplication and virulence in
      the mouse model. The gadC mutant failed to efficiently neutralize the production
      of reactive oxygen species. Remarkably, virulence of the gadC mutant was
      partially restored in mice defective in NADPH oxidase activity. The data
      presented highlight links between glutamate uptake, oxidative stress defense, the
      tricarboxylic acid cycle and phagosomal escape. This is the first report
      establishing the role of an amino acid transporter in the early stage of the
      Francisella intracellular lifecycle. 

PMID- 24453980
TI  - TREM-1 deficiency can attenuate disease severity without affecting pathogen
      clearance.
AB  - Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier
      of pro-inflammatory innate immune reactions. While TREM-1-amplified responses
      likely aid an improved detection and elimination of pathogens, excessive
      production of cytokines and oxygen radicals can also severely harm the host.
      Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock
      or microbial sepsis have so far mostly relied on the administration of TREM-1
      fusion proteins or peptides representing part of the extracellular domain of TREM
      1. However, binding of these agents to the yet unidentified TREM-1 ligand could
      also impact signaling through alternative receptors. More importantly,
      controversial results have been obtained regarding the requirement of TREM-1 for
      microbial control. To unambiguously investigate the role of TREM-1 in homeostasis
      and disease, we have generated mice deficient in Trem1. Trem1(-/-) mice are
      viable, fertile and show no altered hematopoietic compartment. In CD4(+) T cell-
      and dextran sodium sulfate-induced models of colitis, Trem1(-/-) mice displayed
      significantly attenuated disease that was associated with reduced inflammatory
      infiltrates and diminished expression of pro-inflammatory cytokines. Trem1(-/-)
      mice also exhibited reduced neutrophilic infiltration and decreased lesion size
      upon infection with Leishmania major. Furthermore, reduced morbidity was observed
      for influenza virus-infected Trem1(-/-) mice. Importantly, while immune
      associated pathologies were significantly reduced, Trem1(-/-) mice were equally
      capable of controlling infections with L. major, influenza virus, but also
      Legionella pneumophila as Trem1(+/+) controls. Our results not only demonstrate
      an unanticipated pathogenic impact of TREM-1 during a viral and parasitic
      infection, but also indicate that therapeutic blocking of TREM-1 in distinct
      inflammatory disorders holds considerable promise by blunting excessive
      inflammation while preserving the capacity for microbial control. 

PMID- 24453981
TI  - Evolution of chloroplast transcript processing in Plasmodium and its chromerid
      algal relatives.
AB  - It is well understood that apicomplexan parasites, such as the malaria pathogen
      Plasmodium, are descended from free-living algae, and maintain a vestigial
      chloroplast that has secondarily lost all genes of photosynthetic function.
      Recently, two fully photosynthetic relatives of parasitic apicomplexans have been
      identified, the 'chromerid' algae Chromera velia and Vitrella brassicaformis,
      which retain photosynthesis genes within their chloroplasts. Elucidating the
      processes governing gene expression in chromerid chloroplasts might provide
      valuable insights into the origins of parasitism in the apicomplexans. We have
      characterised chloroplast transcript processing pathways in C. velia, V.
      brassicaformis and P. falciparum with a focus on the addition of an unusual, 3'
      poly(U) tail. We demonstrate that poly(U) tails in chromerids are preferentially
      added to transcripts that encode proteins that are directly involved in
      photosynthetic electron transfer, over transcripts for proteins that are not
      involved in photosynthesis. To our knowledge, this represents the first
      chloroplast transcript processing pathway to be associated with a particular
      functional category of genes. In contrast, Plasmodium chloroplast transcripts are
      not polyuridylylated. We additionally present evidence that poly(U) tail addition
      in chromerids is involved in the alternative processing of polycistronic
      precursors covering multiple photosynthesis genes, and appears to be associated
      with high levels of transcript abundance. We propose that changes to the
      chloroplast transcript processing machinery were an important step in the loss of
      photosynthesis in ancestors of parasitic apicomplexans. 

PMID- 24453982
TI  - Genome sequencing highlights the dynamic early history of dogs.
AB  - To identify genetic changes underlying dog domestication and reconstruct their
      early evolutionary history, we generated high-quality genome sequences from three
      gray wolves, one from each of the three putative centers of dog domestication,
      two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup.
      Analysis of these sequences supports a demographic model in which dogs and wolves
      diverged through a dynamic process involving population bottlenecks in both
      lineages and post-divergence gene flow. In dogs, the domestication bottleneck
      involved at least a 16-fold reduction in population size, a much more severe
      bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon
      after their divergence from dogs, implying that the pool of diversity from which
      dogs arose was substantially larger than represented by modern wolf populations.
      We narrow the plausible range for the date of initial dog domestication to an
      interval spanning 11-16 thousand years ago, predating the rise of agriculture. In
      light of this finding, we expand upon previous work regarding the increase in
      copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided
      digestion of starch in agricultural refuse. We find standing variation for
      amylase copy number variation in wolves and little or no copy number increase in
      the Dingo and Husky lineages. In conjunction with the estimated timing of dog
      origins, these results provide additional support to archaeological finds,
      suggesting the earliest dogs arose alongside hunter-gathers rather than
      agriculturists. Regarding the geographic origin of dogs, we find that,
      surprisingly, none of the extant wolf lineages from putative domestication
      centers is more closely related to dogs, and, instead, the sampled wolves form a
      sister monophyletic clade. This result, in combination with dog-wolf admixture
      during the process of domestication, suggests that a re-evaluation of past
      hypotheses regarding dog origins is necessary. 

PMID- 24453983
TI  - Zinc finger transcription factors displaced SREBP proteins as the major Sterol
      regulators during Saccharomycotina evolution.
AB  - In most eukaryotes, including the majority of fungi, expression of sterol
      biosynthesis genes is regulated by Sterol-Regulatory Element Binding Proteins
      (SREBPs), which are basic helix-loop-helix transcription activators. However, in
      yeasts such as Saccharomyces cerevisiae and Candida albicans sterol synthesis is
      instead regulated by Upc2, an unrelated transcription factor with a Gal4-type
      zinc finger. The SREBPs in S. cerevisiae (Hms1) and C. albicans (Cph2) have lost
      a domain, are not major regulators of sterol synthesis, and instead regulate
      filamentous growth. We report here that rewiring of the sterol regulon, with Upc2
      taking over from SREBP, likely occurred in the common ancestor of all
      Saccharomycotina. Yarrowia lipolytica, a deep-branching species, is the only
      genome known to contain intact and full-length orthologs of both SREBP (Sre1) and
      Upc2. Deleting YlUPC2, but not YlSRE1, confers susceptibility to azole drugs.
      Sterol levels are significantly reduced in the YlUPC2 deletion. RNA-seq analysis
      shows that hypoxic regulation of sterol synthesis genes in Y. lipolytica is
      predominantly mediated by Upc2. However, YlSre1 still retains a role in hypoxic
      regulation; growth of Y. lipolytica in hypoxic conditions is reduced in a Ylupc2
      deletion and is abolished in a Ylsre1/Ylupc2 double deletion, and YlSre1
      regulates sterol gene expression during hypoxia adaptation. We show that YlSRE1,
      and to a lesser extent YlUPC2, are required for switching from yeast to
      filamentous growth in hypoxia. Sre1 appears to have an ancestral role in the
      regulation of filamentation, which became decoupled from its role in sterol gene
      regulation by the arrival of Upc2 in the Saccharomycotina. 

PMID- 24453984
TI  - Bioelectric signaling regulates size in zebrafish fins.
AB  - The scaling relationship between the size of an appendage or organ and that of
      the body as a whole is tightly regulated during animal development. If a
      structure grows at a different rate than the rest of the body, this process is
      termed allometric growth. The zebrafish another longfin (alf) mutant shows
      allometric growth resulting in proportionally enlarged fins and barbels. We took
      advantage of this mutant to study the regulation of size in vertebrates. Here, we
      show that alf mutants carry gain-of-function mutations in kcnk5b, a gene encoding
      a two-pore domain potassium (K(+)) channel. Electrophysiological analysis in
      Xenopus oocytes reveals that these mutations cause an increase in K(+)
      conductance of the channel and lead to hyperpolarization of the cell. Further,
      somatic transgenesis experiments indicate that kcnk5b acts locally within the
      mesenchyme of fins and barbels to specify appendage size. Finally, we show that
      the channel requires the ability to conduct K(+) ions to increase the size of
      these structures. Our results provide evidence for a role of bioelectric
      signaling through K(+) channels in the regulation of allometric scaling and
      coordination of growth in the zebrafish. 

PMID- 24453985
TI  - A comprehensive tRNA deletion library unravels the genetic architecture of the
      tRNA pool.
AB  - Deciphering the architecture of the tRNA pool is a prime challenge in translation
      research, as tRNAs govern the efficiency and accuracy of the process. Towards
      this challenge, we created a systematic tRNA deletion library in Saccharomyces
      cerevisiae, aimed at dissecting the specific contribution of each tRNA gene to
      the tRNA pool and to the cell's fitness. By harnessing this resource, we observed
      that the majority of tRNA deletions show no appreciable phenotype in rich medium,
      yet under more challenging conditions, additional phenotypes were observed.
      Robustness to tRNA gene deletion was often facilitated through extensive backup
      compensation within and between tRNA families. Interestingly, we found that
      within tRNA families, genes carrying identical anti-codons can contribute
      differently to the cellular fitness, suggesting the importance of the genomic
      surrounding to tRNA expression. Characterization of the transcriptome response to
      deletions of tRNA genes exposed two disparate patterns: in single-copy families,
      deletions elicited a stress response; in deletions of genes from multi-copy
      families, expression of the translation machinery increased. Our results uncover
      the complex architecture of the tRNA pool and pave the way towards complete
      understanding of their role in cell physiology. 

PMID- 24453986
TI  - Is non-homologous end-joining really an inherently error-prone process?
AB  - DNA double-strand breaks (DSBs) are harmful lesions leading to genomic
      instability or diversity. Non-homologous end-joining (NHEJ) is a prominent DSB
      repair pathway, which has long been considered to be error-prone. However, recent
      data have pointed to the intrinsic precision of NHEJ. Three reasons can account
      for the apparent fallibility of NHEJ: 1) the existence of a highly error-prone
      alternative end-joining process; 2) the adaptability of canonical C-NHEJ (Ku- and
      Xrcc4/ligase IV-dependent) to imperfect complementary ends; and 3) the
      requirement to first process chemically incompatible DNA ends that cannot be
      ligated directly. Thus, C-NHEJ is conservative but adaptable, and the accuracy of
      the repair is dictated by the structure of the DNA ends rather than by the C-NHEJ
      machinery. We present data from different organisms that describe the
      conservative/versatile properties of C-NHEJ. The advantages of the
      adaptability/versatility of C-NHEJ are discussed for the development of the
      immune repertoire and the resistance to ionizing radiation, especially at low
      doses, and for targeted genome manipulation. 

PMID- 24453987
TI  - Defining NELF-E RNA binding in HIV-1 and promoter-proximal pause regions.
AB  - The four-subunit Negative Elongation Factor (NELF) is a major regulator of RNA
      Polymerase II (Pol II) pausing. The subunit NELF-E contains a conserved RNA
      Recognition Motif (RRM) and is proposed to facilitate Poll II pausing through its
      association with nascent transcribed RNA. However, conflicting ideas have emerged
      for the function of its RNA binding activity. Here, we use in vitro selection
      strategies and quantitative biochemistry to identify and characterize the
      consensus NELF-E binding element (NBE) that is required for sequence specific RNA
      recognition (NBE: CUGAGGA(U) for Drosophila). An NBE-like element is present
      within the loop region of the transactivation-response element (TAR) of HIV-1
      RNA, a known regulatory target of human NELF-E. The NBE is required for high
      affinity binding, as opposed to the lower stem of TAR, as previously claimed. We
      also identify a non-conserved region within the RRM that contributes to the RNA
      recognition of Drosophila NELF-E. To understand the broader functional relevance
      of NBEs, we analyzed promoter-proximal regions genome-wide in Drosophila and show
      that the NBE is enriched +20 to +30 nucleotides downstream of the transcription
      start site. Consistent with the role of NELF in pausing, we observe a significant
      increase in NBEs among paused genes compared to non-paused genes. In addition to
      these observations, SELEX with nuclear run-on RNA enrich for NBE-like sequences.
      Together, these results describe the RNA binding behavior of NELF-E and supports
      a biological role for NELF-E in promoter-proximal pausing of both HIV-1 and
      cellular genes. 

PMID- 24453989
TI  - How much is that in dog years? The advent of canine population genomics.

PMID- 24453988
TI  - Genomic confirmation of hybridisation and recent inbreeding in a vector-isolated
      Leishmania population.
AB  - Although asexual reproduction via clonal propagation has been proposed as the
      principal reproductive mechanism across parasitic protozoa of the Leishmania
      genus, sexual recombination has long been suspected, based on hybrid marker
      profiles detected in field isolates from different geographical locations. The
      recent experimental demonstration of a sexual cycle in Leishmania within sand
      flies has confirmed the occurrence of hybridisation, but knowledge of the
      parasite life cycle in the wild still remains limited. Here, we use whole genome
      sequencing to investigate the frequency of sexual reproduction in Leishmania, by
      sequencing the genomes of 11 Leishmania infantum isolates from sand flies and 1
      patient isolate in a focus of cutaneous leishmaniasis in the Cukurova province of
      southeast Turkey. This is the first genome-wide examination of a vector-isolated
      population of Leishmania parasites. A genome-wide pattern of patchy
      heterozygosity and SNP density was observed both within individual strains and
      across the whole group. Comparisons with other Leishmania donovani complex genome
      sequences suggest that these isolates are derived from a single cross of two
      diverse strains with subsequent recombination within the population. This
      interpretation is supported by a statistical model of the genomic variability for
      each strain compared to the L. infantum reference genome strain as well as genome
      wide scans for recombination within the population. Further analysis of these
      heterozygous blocks indicates that the two parents were phylogenetically
      distinct. Patterns of linkage disequilibrium indicate that this population
      reproduced primarily clonally following the original hybridisation event, but
      that some recombination also occurred. This observation allowed us to estimate
      the relative rates of sexual and asexual reproduction within this population, to
      our knowledge the first quantitative estimate of these events during the
      Leishmania life cycle. 

PMID- 24453990
TI  - Developmental link between sex and nutrition; doublesex regulates sex-specific
      mandible growth via juvenile hormone signaling in stag beetles.
AB  - Sexual dimorphisms in trait expression are widespread among animals and are
      especially pronounced in ornaments and weapons of sexual selection, which can
      attain exaggerated sizes. Expression of exaggerated traits is usually male
      specific and nutrition sensitive. Consequently, the developmental mechanisms
      generating sexually dimorphic growth and nutrition-dependent phenotypic
      plasticity are each likely to regulate the expression of extreme structures. Yet
      we know little about how either of these mechanisms work, much less how they
      might interact with each other. We investigated the developmental mechanisms of
      sex-specific mandible growth in the stag beetle Cyclommatus metallifer, focusing
      on doublesex gene function and its interaction with juvenile hormone (JH)
      signaling. doublesex genes encode transcription factors that orchestrate male and
      female specific trait development, and JH acts as a mediator between nutrition
      and mandible growth. We found that the Cmdsx gene regulates sex differentiation
      in the stag beetle. Knockdown of Cmdsx by RNA-interference in both males and
      females produced intersex phenotypes, indicating a role for Cmdsx in sex-specific
      trait growth. By combining knockdown of Cmdsx with JH treatment, we showed that
      female-specific splice variants of Cmdsx contribute to the insensitivity of
      female mandibles to JH: knockdown of Cmdsx reversed this pattern, so that
      mandibles in knockdown females were stimulated to grow by JH treatment. In
      contrast, mandibles in knockdown males retained some sensitivity to JH, though
      mandibles in these individuals did not attain the full sizes of wild type males.
      We suggest that moderate JH sensitivity of mandibular cells may be the default
      developmental state for both sexes, with sex-specific Dsx protein decreasing
      sensitivity in females, and increasing it in males. This study is the first to
      demonstrate a causal link between the sex determination and JH signaling
      pathways, which clearly interact to determine the developmental fates and final
      sizes of nutrition-dependent secondary-sexual characters. 

PMID- 24453991
TI  - Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress
      response pathway protects against oxidative stress.
AB  - The Nrf family of transcription factors mediates adaptive responses to stress and
      longevity, but the identities of the crucial Nrf targets, and the tissues in
      which they function in multicellular organisms to promote survival, are not
      known. Here, we use whole transcriptome RNA sequencing to identify 810 genes
      whose expression is controlled by the SKN-1/Nrf2 negative regulator WDR-23 in the
      nervous system of Caenorhabditis elegans. Among the genes identified is the
      synaptic cell adhesion molecule nlg-1/neuroligin. We find that the synaptic
      abundance of NLG-1 protein increases following pharmacological treatments that
      generate oxidative stress or by the genetic activation of skn-1. Increasing nlg-1
      dosage correlates with increased survival in response to oxidative stress,
      whereas genetic inactivation of nlg-1 reduces survival and impairs skn-1-mediated
      stress resistance. We identify a canonical SKN-1 binding site in the nlg-1
      promoter that binds to SKN-1 in vitro and is necessary for SKN-1 and toxin
      mediated increases in nlg-1 expression in vivo. Together, our results suggest
      that SKN-1 activation in the nervous system can confer protection to organisms in
      response to stress by directly regulating nlg-1/neuroligin expression. 

PMID- 24453995
TI  - Preparation and characterization of di-, tri-, and tetranuclear schiff base
      complexes derived from diamines and 3,4-dihydroxybenzaldehyde.
AB  - A series of new di-, tri-, and tetranuclear Co(II) and Cu(II) complexes of three
      new diSchiff base ligands were synthesized by two different methods. The first
      method involved the synthesis of the three ligands from condensation reaction of
      3,4-dihydroxybenzaldehyde (L'H2) with ethylenediamine (en), o-phenylenediamine (o
      PD), or 4,5-dimethyl-1,2-phenylendiamine (DMPD) in a mole ratio of 2 : 1 followed
      by the reaction of the resulting Schiff bases ligands with Cu(II) or Co(II) ions
      in the presence of 2,2'-bipyridyl (L) to form the di- and trinuclear metal
      complexes. The second method involved the condensation of the copper complex
      LCu(II)L' (L = 2,2'-bipyridyl, L' = 4-formylbenzene-1,2-bis(olate)) with en, o
      PD, or DMPD in a mole ratio of 2 : 1, respectively, followed by reaction with
      CuCl2 or Cu(ClO4)2 to form di-, tri-, and tetranuclear copper (II) complexes,
      respectively. The structures of the ligands and metal complexes were
      characterized by elemental analyses, NMR, and FTIR spectra. The geometries of
      metal complexes were suggested according to elemental analysis, electronic
      spectra, thermal analyses, atomic absorption, and magnetic moments and
      conductivity measurements. 

PMID- 24453992
TI  - Cell-cycle dependent expression of a translocation-mediated fusion oncogene
      mediates checkpoint adaptation in rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood.
      Most rhabdomyosarcoma falls into one of two biologically distinct subgroups
      represented by alveolar or embryonal histology. The alveolar subtype harbors a
      translocation-mediated PAX3:FOXO1A fusion gene and has an extremely poor
      prognosis. However, tumor cells have heterogeneous expression for the fusion
      gene. Using a conditional genetic mouse model as well as human tumor cell lines,
      we show that that Pax3:Foxo1a expression is enriched in G2 and triggers a
      transcriptional program conducive to checkpoint adaptation under stress
      conditions such as irradiation in vitro and in vivo. Pax3:Foxo1a also tolerizes
      tumor cells to clinically-established chemotherapy agents and emerging
      molecularly-targeted agents. Thus, the surprisingly dynamic regulation of the
      Pax3:Foxo1a locus is a paradigm that has important implications for the way in
      which oncogenes are modeled in cancer cells. 

PMID- 24453993
TI  - Evolutionary rate covariation identifies new members of a protein network
      required for Drosophila melanogaster female post-mating responses.
AB  - Seminal fluid proteins transferred from males to females during copulation are
      required for full fertility and can exert dramatic effects on female physiology
      and behavior. In Drosophila melanogaster, the seminal protein sex peptide (SP)
      affects mated females by increasing egg production and decreasing receptivity to
      courtship. These behavioral changes persist for several days because SP binds to
      sperm that are stored in the female. SP is then gradually released, allowing it
      to interact with its female-expressed receptor. The binding of SP to sperm
      requires five additional seminal proteins, which act together in a network.
      Hundreds of uncharacterized male and female proteins have been identified in this
      species, but individually screening each protein for network function would
      present a logistical challenge. To prioritize the screening of these proteins for
      involvement in the SP network, we used a comparative genomic method to identify
      candidate proteins whose evolutionary rates across the Drosophila phylogeny co
      vary with those of the SP network proteins. Subsequent functional testing of 18
      co-varying candidates by RNA interference identified three male seminal proteins
      and three female reproductive tract proteins that are each required for the long
      term persistence of SP responses in females. Molecular genetic analysis showed
      the three new male proteins are required for the transfer of other network
      proteins to females and for SP to become bound to sperm that are stored in mated
      females. The three female proteins, in contrast, act downstream of SP binding and
      sperm storage. These findings expand the number of seminal proteins required for
      SP's actions in the female and show that multiple female proteins are necessary
      for the SP response. Furthermore, our functional analyses demonstrate that
      evolutionary rate covariation is a valuable predictive tool for identifying
      candidate members of interacting protein networks. 

PMID- 24453996
TI  - Coordination dynamics and coordination mechanism of a new type of anticoagulant
      diethyl citrate with ca(2+) ions.
AB  - Diethyl citrate (Et2Cit) is a new potential anticoagulant. The coordination
      dynamics and coordination mechanism of Et2Cit with Ca(2+) ions and the effect of
      pH on the complex were examined. The result was compared with that for the
      conventional anticoagulant sodium citrate (Na3Cit). The reaction order (n) of
      Et2Cit and Na3Cit with Ca(2+) was 2.46 and 2.44, respectively. The reaction rate
      constant (k) was 120 and 289 L.mol(-1) .s(-1). The reverse reaction rate constant
      (k re) was 0.52 and 0.15 L.mol(-1) .s(-1), respectively. It is indicated that the
      coordination ability of Et2Cit with Ca(2+) was weaker than that of Na3Cit.
      However, the dissociation rate of the calcium complex of Et2Cit was faster than
      that of Na3Cit. Increased pH accelerated the dissociation rate of the complex and
      improved its anticoagulant effect. The Et2Cit complex with calcium was
      synthesized and characterized by elemental analysis, XRD, FT-IR, (1)H NMR, and
      ICP. These characteristics indicated that O in -COOH and C-O-C of Et2Cit was
      coordinated with Ca(2+) in a bidentate manner with 1 : 1 coordination proportion;
      that is, complex CaEt2Cit was formed. Given that CaEt2Cit released Ca(2+) more
      easily than Na3Cit, a calcium solution was not needed in intravenous infusions
      using Et2Cit as anticoagulant unlike using Na3Cit. Consequently, hypocalcemia and
      hypercalcemia were avoided. 

PMID- 24453998
TI  - Effect of dose escalation with single opioid, fentanyl matrix in patients not
      controlling cancer pain: a multicenter, prospective, observational study in
      Korea.
AB  - PURPOSE: End-of-dose failure (EOD) is a clinically common observation and many
      cancer patients increase the frequency of opioid administration. Fentanyl matrix
      use is known to be effective in patients with chronic cancer pain. To measure the
      effectiveness of increase in a single dose of fentanyl matrix in patients whose
      pain was not controlled sufficiently, we perform this study. MATERIALS AND
      METHODS: A multi-center, open-label, prospective, observational study was
      conducted in 30 hospitals in Korea, between August and December 2008. RESULTS: A
      total of 452 patients were enrolled; 404 patients completed the study. The mean
      pain intensity decreased from 5.27 at the first visit to 3.37 at the end of the
      trial. There was a significant difference in pain intensity (p < 0.001) between
      the first and last visits. The percentage of pain intensity difference was 30.1%.
      The prevalence of EOD at the first visit was 73% from the 452 enrolled patients.
      After the use of fentanyl patch, EOD decreased from 73% to 56%. Pain intensity of
      patients experiencing EOD was 5.64 at the baseline compared to 4.27 in patients
      without EOD. On final visit, pain intensity in patients with and without EOD was
      4.02 and 2.54, respectively. The observed adverse events were mainly nausea,
      asthenia, constipation and diarrhea. CONCLUSION: This study demonstrated that
      increasing dose of fentanyl patch decreased pain intensity and decreased the rate
      of patients experiencing EOD. Thus, fentanyl patch may be an effective modality
      in cancer patients whose pain was previously not controlled sufficiently; the
      side effects were as could be expected with an opioid.

PMID- 24453997
TI  - Targeting arginine-dependent cancers with arginine-degrading enzymes:
      opportunities and challenges.
AB  - Arginine deprivation is a novel antimetabolite strategy for the treatment of
      arginine-dependent cancers that exploits differential expression and regulation
      of key urea cycle enzymes. Several studies have focused on inactivation of
      argininosuccinate synthetase 1 (ASS1) in a range of malignancies, including
      melanoma, hepatocellular carcinoma (HCC), mesothelial and urological cancers,
      sarcomas, and lymphomas. Epigenetic silencing has been identified as a key
      mechanism for loss of the tumor suppressor role of ASS1 leading to tumoral
      dependence on exogenous arginine. More recently, dysregulation of
      argininosuccinate lyase has been documented in a subset of arginine auxotrophic
      glioblastoma multiforme, HCC and in fumarate hydratase-mutant renal cancers.
      Clinical trials of several arginine depletors are ongoing, including pegylated
      arginine deiminase (ADI-PEG20, Polaris Group) and bioengineered forms of human
      arginase. ADI-PEG20 is furthest along the path of clinical development from
      combinatorial phase 1 to phase 3 trials and is described in more detail. The
      challenge will be to identify tumors sensitive to drugs such as ADI-PEG20 and
      integrate these agents into multimodality drug regimens using imaging and
      tissue/fluid-based biomarkers as predictors of response. Lastly, resistance
      pathways to arginine deprivation require further study to optimize arginine
      targeted therapies in the oncology clinic. 

PMID- 24453999
TI  - Trends in the Aggressiveness of End-of-Life Care for Advanced Stomach Cancer
      Patients.
AB  - PURPOSE: It is important to balance the appropriateness of active cancer
      treatments and end-of-life care to improve the quality of life for terminally ill
      cancer patients. This study describes the treatment patterns and end-of-life care
      in terminal gastric cancer patients. MATERIALS AND METHODS: We retrospectively
      analyzed the records of 137 patients with advanced gastric cancer receiving
      chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded
      interval between last chemotherapy dose and death; frequency of emergency room
      visits or admission to the intensive care unit in the last month before death;
      rate of hospice referral and agreement with written do-not-resuscitate orders;
      and change in laboratory values in the last three months before death. RESULTS:
      During the last six months of life, 130 patients (94.9%) received palliative
      chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final
      month. During the final month, 53 patients (38.7%) visited an emergency room more
      than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral
      occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written
      do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine
      changed significantly two weeks before death; total bilirubin, one month before;
      and C-reactive protein, between four and two weeks before death. CONCLUSION: Our
      results demonstrated that a significant proportion of gastric cancer patients
      received palliative chemotherapy to the end of life and the patients who stopped
      the chemotherapy at least one month before death had a lower rate of intensive
      care unit admission and longer overall survival than those who sustained
      aggressive chemotherapy until the last months of their lives.

PMID- 24454000
TI  - Clinical prognostic factors for locally advanced esophageal squamous carcinoma
      treated after definitive chemoradiotherapy.
AB  - PURPOSE: Locally advanced esophageal cancers are generally treated with
      neoadjuvant chemoradiotherapy, followed by surgery in operable candidates.
      However, even if the patients were diagnosed as operable disease, surgery could
      not be performed on patients with poor condition or other comorbidity. In this
      case, definitive chemoradiotherapy (dCRT) is the other option for localized
      esophageal cancer. Therefore, the purpose of this study was to evaluate the
      efficacy and clinical prognostic factors for dCRT in locally advanced esophageal
      cancer. MATERIALS AND METHODS: We conducted a review of patients who received
      dCRT for locally advanced squamous esophageal cancer from 2004 to 2010, focusing
      on stages III and IVa. All patients received at least two cycles of platinum
      based chemotherapy during radiation, and all tumor burdens were included in the
      radiation field. The treatment results were analyzed for patterns of failure and
      prognostic factors associated with survival. RESULTS: In total, 63 patients were
      enrolled in this study. The overall response rate was 84.1%. Relief from
      dysphagia after dCRT was achieved in 48 patients. The most frequent failure was
      local recurrence. The median overall survival (OS) was 23.0 months, and the 2
      year survival rate was 45.4%. Similar results were observed for elderly study
      patients. Significant prognostic factors for OS were duration of smoking, high
      grade of dysphagia (score of 3 or 4), and shorter duration of progression-free
      and dysphagia-free survival. Maintenance chemotherapy after dCRT did not
      influence OS. However, "good risk" patients receiving maintenance chemotherapy
      showed better OS than those who did not receive maintenance chemotherapy (30.4
      months vs. 12.0 months, p=0.002). CONCLUSION: dCRT has a major role in improving
      survival and palliation of dysphagia in inoperable advanced esophageal cancer,
      even in elderly patients. Maintenance chemotherapy after dCRT may be effective in
      prolonging survival in "good risk" patients.

PMID- 24454001
TI  - Nomogram to predict treatment outcome of fluoropyrimidine/platinum-based
      chemotherapy in metastatic esophageal squamous cell carcinoma.
AB  - PURPOSE: The degree of benefit from palliative chemotherapy differs widely among
      patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose
      of this study was to develop and validate a prognostic nomogram to predict
      survival and aid physicians and patients in the decision-making process regarding
      treatment options. MATERIALS AND METHODS: Clinicopathologic variables and
      treatment outcomes of 239 patients who were diagnosed with MESCC and received
      either fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) as first-line
      chemotherapy were reviewed. A nomogram was developed as a prognostic scoring
      system incorporating significant clinical and laboratory variables based on a
      multivariate Cox proportional hazards regression model. An independent series of
      61 MESCC patients treated with FP served as an independent data set for nomogram
      validation. RESULTS: No difference in response rate was observed between the FP
      group (44.8%) and the XP group (54.2%). Similarly, no significant differences in
      median progression-free survival and median overall survival were observed
      between regimen groups. Multivariate analysis showed that poor performance status
      (Eastern Cooperative Oncology Group [ECOG] status>=2), weight loss (10% of the
      weight loss for 3 months), low albumin level (<=3.5 g/dL), and absence of
      previous esophagectomy at the time of chemotherapy were significantly associated
      with low OS in both groups (p<0.05). Based on these findings, patients were
      classified into favorable (score, 0 to 90), intermediate (91-134), and poor
      (>135) prognostic groups. The median survival for those with a favorable ECOG was
      13.8 months (95% confidence interval [CI], 10.8 to 18.6 months), for intermediate
      11.2 months (95% CI, 8.7 to 11.9 months), and for poor, 7.0 months (95% CI, 3.6
      to 10.0 months). External validation of the nomogram in a different patient
      cohort yielded significantly similar findings. CONCLUSION: The nomogram described
      here predicts survival in MESCC patients and could serve as a guide for the use
      of FP/XP chemotherapy in MESCC patients.

PMID- 24454002
TI  - Predictive factors for radiation pneumonitis in lung cancer treated with helical
      tomotherapy.
AB  - PURPOSE: Predictive factors for radiation pneumonitis (RP) after helical
      tomotherapy (HT) may differ from those after linac-based radiotherapy. In this
      study, we identified predictive factors for RP in patients with lung cancer
      treated with HT. MATERIALS AND METHODS: We retrospectively analyzed clinical,
      treatment-related and dosimetric factors from 31 patients with lung cancer
      treated with HT. RP was graded according to Common Terminology Criteria for
      Adverse Events version 4.0 and grade >=2 RP was defined as a RP event. We used
      Kaplan-Meier methods to compute the actuarial incidence of RP. For univariate and
      multivariate analysis, the log-rank test and the Cox proportional regression
      hazard model were used. We generated receiver-operating characteristics (ROC)
      curves to define the cutoff values for significant parameters. RESULTS: The
      median follow-up duration was 6.6 months (range, 1.6 to 38.5 months). The 2-, 4-,
      and 6-month actuarial RP event rates were 13.2%, 58.5%, and 67.0%, respectively.
      There was no grade 4 or more RP. Ipsilateral V5, V10, V15, and contralateral V5
      were related with RP event on univariate analysis. By multivariate analysis,
      ipsilateral V10 was factor most strongly associated with RP event. On the ROC
      curve, the cutoff values of ipsilateral V5, V10, V15, and contralateral V5 were
      67.5%, 58.5%, 50.0%, and 55.5%, respectively. CONCLUSION: In our study,
      ipsilateral V5, V10, V15, and contralateral V5 were significant predictive
      factors for RP after HT.

PMID- 24454003
TI  - Immunogenicity of influenza vaccine in colorectal cancer patients.
AB  - PURPOSE: Although influenza is regarded as a major cause of morbidity and
      mortality in immunocompromised patients, vaccine coverage remains poor. We
      evaluated the immunogenicity of influenza vaccines in colorectal cancer patients.
      MATERIALS AND METHODS: In this study, 40 colorectal cancer patients who received
      an influenza vaccine at the Korea Cancer Center Hospital during the 2009-2010 and
      2010-2011 influenza seasons were analyzed. The blood samples were collected at
      prevaccination and 30 days post vaccination, and antibody titers were measured
      using the hemagglutination-inhibition tests. RESULTS: In the 2009-2011 season,
      the seroprotection rate for H1N1 (94.7%) was significantly higher than that for
      H3N2 (42.1%) and B (47.3%). The seroconversion rate was 52.6%, 26.3%, and 36.8%
      for H1N1, H3N2, and B, respectively. Fold increase of geometric mean titer (MFI)
      was 3.86, 1.49, and 3.33 for H1N1, H3N2, and B, respectively. In the 2010-2011
      season, the seroprotection rate for H1N1 (57.1%) was significantly higher than
      that for H3N2 (52.4%) and B (38.1%). The seroconversion rate was 52.4%, 47.6% and
      33.3% for H1N1, H3N2, and B, respectively. MFI was 12.29, 3.62 and 4.27 for H1N1,
      H3N2, and B, respectively. CONCLUSION: Our study cohort showed an acceptable
      immune response to an influenza vaccine without significant adverse effects,
      supporting the recommendation for annual influenza vaccination in colorectal
      cancer patients.

PMID- 24454004
TI  - Effects of polymorphisms of innate immunity genes and environmental factors on
      the risk of noncardia gastric cancer.
AB  - PURPOSE: Increasing evidence suggests that polymorphisms in innate immunity genes
      are associated with Helicobacter pylori-induced inflammation and may influence
      susceptibility in developing noncardia gastric cancer. Therefore, we investigate
      the effect of polymorphisms of innate immunity genes and interactions with
      environmental factors in the Korean population. MATERIALS AND METHODS: We
      genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and
      rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia
      gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous
      logistic regression models were used to detect the effects of genetic
      polymorphisms and environmental factors, which were stratified by the
      histological type of gastric cancer. RESULTS: TLR4 rs10983755 A carriers were
      found to have higher risk of intestinal-type noncarida gastric cancer than G
      homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97),
      but other genetic variants showed no association with the risk of noncardia
      gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4
      rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking
      TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition,
      compared with tap water, other drinking water sources during childhood were found
      to be associated with the elevated risk of intestinal-type gastric cancer, and
      these associations were slightly stronger among TLR4 rs10983755 A carriers.
      CONCLUSION: The genetic polymorphisms of innate immunity genes are associated
      with the development of intestinal-type noncardia gastric cancer and these
      associations may differ in accordance to an exposure to certain environmental
      factors.

PMID- 24454005
TI  - Clinical Implications of VEGF, TGF-beta1, and IL-1beta in Patients with Advanced
      Non-small Cell Lung Cancer.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF)-A, VEGF165b, interleukin (IL)
      1beta, and transforming growth factor (TGF)-beta1 are known to influence tumor
      angiogenesis. Clinical implications of these cytokines need to be elucidated.
      MATERIALS AND METHODS: Using clinical data and baseline serum samples of 140
      consecutive patients with advanced non-small cell lung cancer who received
      platinum-based combination chemotherapy, we investigated the association among
      serum cytokine levels, treatment outcomes, as well as leukocyte and platelet
      counts. RESULTS: The median age of patients was 64 years (range, 26 to 86 years).
      The male to female ratio was 104:36. High TGF-beta1 and IL-1beta levels were
      associated with shorter progression-free survival, and high VEGF-A and IL-1beta
      levels were associated with shorter overall survival in the univariate analysis.
      VEGF165b was not related to the treatment outcomes. Leukocytosis and
      thrombocytosis were associated with shorter overall survival. The multivariate
      analysis demonstrated that VEGF-A, IL-1beta, and leukocytosis were significant
      prognostic factors (p=0.0497, p=0.047, and p<0.001, respectively). Leukocytosis
      was not associated with recent pneumonia (p=0.937) and correlated with VEGF-A
      (p<0.001) and TGF-beta1 (p=0.020) levels. CONCLUSION: Serum VEGF-A, TGF-1beta,
      and IL-1beta levels, in addition to leukocyte and platelet counts, are shown to
      be associated with clinical outcomes. Leukocyte and platelet counts are
      correlated with serum VEGF-A and TGF-beta1 levels.

PMID- 24454006
TI  - Sequence-Dependent Radiosensitization of Histone Deacetylase Inhibitors
      Trichostatin A and SK-7041.
AB  - PURPOSE: This preclinical study is to determine whether the capacity of histone
      deacetylase (HDAC) inhibitors to enhance radiation response depends on temporal
      sequences of HDAC inhibition and irradiation. MATERIALS AND METHODS: The effects
      of HDAC inhibitors trichostatin A (TSA) and SK-7041 on radiosensitivity in human
      lung cancer cells were examined using a clonogenic assay, exposing cells to HDAC
      inhibitors in various sequences of HDAC inhibition and radiation. We performed
      Western blot of acetylated histone H3 and flow cytometry to analyze cell cycle
      phase distribution. RESULTS: TSA and SK-7041 augmented radiation cell lethality
      in an exposure time-dependent manner when delivered before irradiation. The
      impact of TSA and SK-7041 on radiosensitivity rapidly diminished when HDAC
      inhibition was delayed after irradiation. Radiation induced the acetylation of
      histone H3 in cells exposed to TSA, while irradiation alone had no effect on the
      expression of acetylated histone H3 in TSA-naive cells. Preirradiation exposure
      to TSA abrogated radiation-induced G2/M-phase arrest. When delivered after
      irradiation, TSA had no effect on the peak of radiation-induced G2/M-phase
      arrest. CONCLUSION: TSA and SK-7041 enhances radiosensitivity only when delivered
      before irradiation. Unless proven otherwise, it seems prudent to apply scheduling
      including preirradiation HDAC inhibition so that maximal radiosensitization is
      obtained.

PMID- 24454007
TI  - Tumor lysis syndrome in a solid tumor: a case report of a patient with invasive
      thymoma.
AB  - Tumor lysis syndrome (TLS) has rarely been observed in solid tumors. We report on
      a case of a patient with advanced invasive thymoma who developed tumor lysis
      syndrome after chemotherapy. The potential complications of TLS should be
      considered in treatment of extensive thymoma. 

PMID- 24454008
TI  - Sunitinib treatment for metastatic renal cell carcinoma in patients with von
      hippel-lindau disease.
AB  - Von Hippel-Lindau (VHL) disease is an autosomal dominant disease that produces a
      variety of tumors and cysts in the central nervous system and visceral organs,
      including renal cell carcinoma (RCC). RCC in patients with VHL disease does not
      frequently metastasize, therefore, the response to treatment and prognosis of
      metastatic RCC developed in patients with VHL disease has not been reported.
      Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor with
      antiangiogenic and antitumor activity. Here, we report on four patients with
      metastatic RCC in VHL disease who received sunitinib and achieved partial
      responses that have lasted for a prolonged period of time. 

PMID- 24454009
TI  - Sarcoidosis mimicking cancer metastasis following chemotherapy for ovarian
      cancer.
AB  - We report on a rare case of sarcoidosis that developed after chemotherapy for
      ovarian cancer, and mimicked a cancer metastasis. A 52-year-old female diagnosed
      with stage III ovarian cancer underwent curative surgery and postoperative
      chemotherapy. Four months later, her whole-body positron emission tomography and
      computed tomography (CT) scan showed high uptake in the mediastinal lymph nodes,
      and ovarian cancer recurrence was suspected. Biopsy of the mediastinal lymph
      nodes and subcutaneous nodules revealed noncaseating granulomas. These lesions
      resolved spontaneously without treatment; however, newly developed perilymphatic
      and centrilobular nodules were observed on follow-up chest CT. Surgical biopsy of
      these lesions also showed noncaseating granulomas. She was finally diagnosed with
      sarcoidosis. 

PMID- 24454010
TI  - RbH2AsO4.
AB  - RbH2AsO4, rubidium di-hydrogenarsenate (RDA), was synthesized by partial
      neutralization of an aqueous H3AsO4 solution with aqueous Rb2CO3. Its
      paraelectric room-temperature phase is composed of virtually regular tetra-hedral
      [AsO2(OH)2](-) anions and Rb(+) cations, both located on -4 positions. The
      [AsO2(OH)2] units are connected via O-H?O hydrogen bonds into a three-dimensional
      network, whereby the H atoms are equally disordered between the O atoms. The
      Rb(+) cations are located in channels running along the <100> directions and
      coordinated by eight O atoms located at the vertices of a snub disphenoid. 

PMID- 24454011
TI  - Olivine-type NaCd(AsO4).
AB  - The title compound, sodium cadmium orthoarsenate, adopts the olivine [Mg2(SiO4)]
      structure type in space group Pnma, with Na (site symmetry -1) and Cd (.m.)
      replacing the two Mg positions, and the AsO4 tetra-hedron (.m.) the SiO4 tetra
      hedron. The crystal structure is made up of a nearly hexa-gonal closed-packed
      arrangement of O atoms stacked along [001]. The Na and Cd atoms occupy one half
      of the octa-hedral voids in alternate layers stacked along [100], and one eighth
      of the tetra-hedral voids are occupied by As atoms. 

PMID- 24454012
TI  - Thulium nickel/lithium distannide, TmNi1-x Li x Sn2 (x = 0.035).
AB  - The quaternary thulium nickel/lithium distannide, TmNi1-x Li x Sn2 (x = 0.035),
      crystallizes in the ortho-rhom-bic LuNiSn2 structure type. The asymmetric unit
      contains three Tm sites, six Sn sites, two Ni sites and one Ni/Li site [relative
      occupancies = 0.895 (8):0.185 (8)]. Site symmetries are .m. for all atoms. The 17
      , 18- and 19-vertex distorted pseudo-Frank-Kasper polyhedra are typical for all
      Tm atoms. Four Sn atoms are enclosed in a 12-vertex deformed cubo-octa-hedron,
      and another Sn atom is enclosed in a penta-gonal prism with three added atoms. A
      tricapped trigonal prism is typical for a further Sn atom. The coordination
      number for all Ni atoms and Ni/Li statistical mixtures is 12 (fourcapped trigonal
      prism [Ni/LiTm5Sn5]). Tm atoms form the base of a prism and Ni/Li atoms are at
      the centres of the side faces of an [SnTm6Ni/Li3] prism. These isolated prisms
      are implemented into three-dimensional-nets built out of Sn atoms. Electronic
      structure calculations using TB-LMTO-ASA suggest that the Tm and Ni/Li atoms form
      positively charged n[TmNi/Li] (m+) polycations which compensate the negative
      charge of 2n[Sn] (m-) polyanions. Analysis of the inter-atomic distances and
      electronic structure calculations indicate the dominance of a metallic type of
      bonding. 

PMID- 24454013
TI  - Sodium selenite penta-hydrate, Na2SeO3.5H2O.
AB  - In the crystal structure of Na2SeO3.5H2O [disodium selen-ate(IV) penta-hydrate],
      two Se, two selenite O atoms and one water O atom are located on a mirror plane,
      and one water O atom is located on a twofold rotation axis. The coordination of
      one Na(+) cation is distorted trigonal bipyramidal, formed by three equatorial
      H2O ligands and two axial selenite O atoms. The other Na(+) cation has an octa
      hedral coordination by six water mol-ecules. The two independent SeO3 groups form
      almost undistorted trigonal pyramids, with Se-O bond lengths in the range 1.6856
      (7)-1.7202 (10) A and O-Se-O angles in the range 101.98 (3)-103.11 (5) degrees ,
      and both are MU2-O:O-bonded to a pair of Na(+) cations. Hydrogen bonds involving
      all water molecules and selenite O atoms consolidate the crystal packing.
      Although anhydrous Na2SeO3 and Na2TeO3 are isotypic, the title compound is
      surprisingly not isotypic with Na2TeO3.5H2O. In the tellurite hydrate, all Na(+)
      cations have an octa-hedral coordination and the TeO3 groups are bonded to Na(+)
      only via one of their three O atoms. 

PMID- 24454014
TI  - A triclinic polymorph of dicadmium divanadate(V).
AB  - The title compound, Cd2V2O7, was obtained under hydro-thermal conditions.
      Different from the known monoclinic form, the new polymorph of Cd2V2O7 has
      triclinic symmetry and is isotypic with Ca2V2O7. The building units of the
      crystal structure are two Cd(2+) cations, with coordination numbers of six and
      seven, and two V atoms with a tetra-hedral and a significantly distorted trigonal
      pyramidal coordination environment, respectively. Two VO5 pyramids share an edge
      and each pyramid is connected to one VO4 tetra-hedron via a corner atom, forming
      an isolated V4O14 (8-) anion. These anions are arranged in sheets parallel to (
      211) and are linked through the Cd(2+) cations into a three-dimensional framework
      structure. 

PMID- 24454015
TI  - Redetermination of Dy3Ni from single-crystal X-ray data.
AB  - The classification of the title compound, tridysprosium nickel, into the Fe3C (or
      Al3Ni) structure type has been deduced from powder X-ray diffraction data with
      lattice parameters reported in a previous study [Lemaire & Paccard (1967 ?).
      Bull. Soc. Fr. Mineral. Cristallogr. 40, 311-315]. The current re-investigation
      of Dy3Ni based on single-crystal X-ray data revealed atomic positional parameters
      and anisotropic displacement parameters with high precision. The asymmetric unit
      consists of two Dy and one Ni atoms. One Dy atom has site symmetry .m. (Wyckoff
      position 4c) and is surrounded by twelve Dy and three Ni atoms. The other Dy atom
      (site symmetry 1, 8d) has eleven Dy and three Ni atoms as neighbours, forming a
      distorted Frank-Kasper polyhedron. The coordination polyhedron of the Ni atom
      (.m., 4c) is a tricapped trigonal prism formed by nine Dy atoms. 

PMID- 24454016
TI  - catena-Poly[2,2',2''-nitrilo-tris-(ethan-aminium) [tri-MU-oxido-tris-[dioxido
      vanadate(V)]] monohydrate].
AB  - The title compound, {(C6H21N4)[V3O9].H2O} n , crystallizes as a salt with
      [trenH3](3+) cations [tren is tris-(2-amino-eth-yl)amine], and one-dimensional
      anionic {[V(V)O3](-)} n (metavanadate) chains along the c-axis direction. Three
      crystallographically distinct V(V) sites and one occluded water mol-ecule are
      present for every [trenH3](3+) cation in the unit cell. The {[V(V)O3](-)} n
      chains are composed of vertex-sharing [VO4] tetra-hedra and have a repeat unit of
      six tetra-hedra. Each tetra-hedron in the chain contains two terminal and two
      MU(2)-bridging oxide ligands. The [trenH3](3+) cations, {[V(V)O3](-)} n anions
      and occluded water mol-ecules participate in an extensive three-dimensonal
      hydrogen-bonding network. The three terminal ammonium sites of the [trenH3](3+)
      cations each form strong N-H?O hydrogen bonds to terminal oxide ligands on the
      {[V(V)O3](-)} n chain. Each occluded water mol-ecule also donates two O-H?O
      hydrogen bonds to the terminal oxide ligands. 

PMID- 24454017
TI  - Bis(2-meth-oxy-benzyl-ammonium) di-aqua-bis-(di-hydrogen diphosphato-kappa(2)
      O,O')manganate(II) dihydrate.
AB  - The asymmetric unit of the title compound, (C8H12NO)2[Mn(H2P2O7)2(H2O)2].2H2O,
      consists of half an Mn(II) complex anion, a 2-meth-oxy-benyl-ammonium cation and
      a solvent water mol-ecule. The Mn(II) complex anion lies across an inversion
      center, and has a slightly distorted octa-hedral coordination environment for the
      Mn(II) ion, formed by two bidentate dihydrogendiphosphate ligands and two water
      mol-ecules. In the crystal, the components are linked by O-H?O and N-H?O hydrogen
      bonds, forming layers parallel to (100). An intra-molecular N-H?O hydrogen bond
      is also observed. 

PMID- 24454018
TI  - Poly[[MU-chlorido-MU-[2-(2,4-di-fluoro-phen-yl)-1,3-bis-(1,2,4-triazol-1
      yl)propan-2-ol-kappa(2) N (4):N (4')]-zinc] chloride dihydrate].
AB  - The title compound, {[ZnCl(C13H12F2N6O)2]Cl.2H2O} n , is a two-dimensional
      coordination polymer. The Zn(II) atom is six-coordinated by four N atoms from
      four 2-(2,4-di-fluoro-phen-yl)-1,3-bis-(1,2,4-triazol-1-yl)propan-2-ol (HFlu)
      ligands and by two Cl atoms in a distorted octa-hedral geometry. Two Cl atoms
      bridge two Zn(II) atoms, forming a centrosymmetric dinuclear unit. The HFlu
      ligands connect the dinuclear units into a 4(4) net parallel to (001) when the
      dinuclear unit is considered as a node. O-H?O and O-H?Cl hydrogen bonds link the
      cationic layer, free chloride anions and lattice water mol-ecules. Intra-layer pi
      pi inter-actions between the triazole rings are observed [centroid-centroid
      distance = 3.716 (6) A]. 

PMID- 24454019
TI  - Bis[MU-3,5-bis-(pyridin-2-yl)-1H-pyrazole]-bis-[di-bromido-iron(III)].
AB  - The title dinuclear complex, [Fe2Br4(C13H9N4)2], which lies on an inversion
      center, features two approximately planar bis-(pyridin-2-yl)pyrazole (bpypz(-))
      ligands [maximum deviation = 0.082 (3) A] and four bromide ions. Each Fe(III) ion
      is octa-hedrally coordinated by four N atoms of two bpypz(-) ligands and two Br
      ions. pi-pi stacking inter-actions [centroid-centroid distances = 3.7004 (17)
      4.0123 (18) A] are observed between pyridyl and pyrazole rings, and between
      pyridyl and pyridyl rings of adjacent complex mol-ecules. 

PMID- 24454020
TI  - Bis[MU-N-(pyridin-2-ylmeth-yl)pyridin-3-amine-kappa(2) N:N']disilver(I) bis
      (perchlorate) dimethyl sulfoxide disolvate.
AB  - In the binuclear title compound, [Ag2(C11H11N3)2](ClO4)2.2C2H6SO, the complex
      cation is centrosymmetric, with the unique Ag(I) cation coordinated by two
      pyridine N atoms from two symmetry-related N-(pyridine-2-ylmeth-yl)pyridine-3
      amine ligands in a geometry slightly distorted from linear [N-Ag-N = 170.78 (9)
      degrees ], resulting in the formation of a 16-membered cyclic dimer. The two
      pyridine rings coordinating to the Ag(I) atom are almost perpendicular to each
      other [dihedral angle = 87.73 (10) degrees ]. Inter-molecular Ag?O inter-actions
      [3.149 (3) and 2.686 (3) A], N-H?O and C-H?O hydrogen bonds and C-H?pi inter
      actions between the cyclic dimers and the anions or the solvent mol-ecules lead
      to the formation of a three-dimensional supra-molecular network. 

PMID- 24454021
TI  - Poly[bis-(ethanol)(MU4-2,3,5,6-tetra-fluoro-benzene-1,4-di-carboxyl-ato)cadmium].
AB  - In the title compound, [Cd(C8F4O4)(C2H5OH)2] n , the Cd(II) cation sits on an
      inversion centre and is coordinated by six O atoms from four tetra-fluoro-benzene
      1,4-di-carboxyl-ate anions and two ethanol mol-ecules in a distorted octa-hedral
      geometry. The anionic ligand is also located on an inversion centre, and connects
      four Cd(II) cations, generating a two-dimensional polymeric layer parallel to the
      ab plane. Within the layer, the ethanol mol-ecule links F and O atoms of the
      nearest anionic ligands via O-H?O and O-H?F hydrogen bonds. The ethyl group of
      the ethanol mol-ecule is disordered over two positions with an occupancy ratio of
      0.567 (10):0.433 (10). 

PMID- 24454022
TI  - Tris(cyclo-hexyl-ammonium) cis-di-chlorido-bis-(oxalato-kappa(2) O (1),O
      (2))stann-ate(IV) chloride monohydrate.
AB  - The crystal structure of the title compound, (C6H14N)3[Sn(C2O4)2Cl2]Cl.H2O,
      contains three cyclo-hexyl-ammonium cations, one stannate(IV) dianion, one
      isolated chloride anion and one lattice water mol-ecule. The cyclo-hexyl-ammonium
      cations adopt chair conformations. In the complex anion, two bidentate oxalate
      ligands and two chloride anions in cis positions coordinate octa-hedrally to the
      central Sn(IV) atom. The cohesion of the mol-ecular entities is ensured by the
      formation of N-H?O, O-H?O, O-H?Cl and N-H?Cl inter-actions involving cations,
      anions and the lattice water mol-ecule, giving rise to a layer-like arrangement
      parallel to (010). 

PMID- 24454023
TI  - Bis(MU-l-arginine-kappa(3) N (2),O:O')bis-(l-arginine-kappa(2) N (2),O)tetra-MU
      chlorido-tetra-chlorido-tetra-copper(II).
AB  - The title compound, [Cu4Cl8(C6H14N4O2)4], contains four mol-ecules in the
      asymmetric unit. In the mol-ecular structure, each of the four Cu(2+) ions binds
      to three Cl atoms, one N atom and one O atom, resulting in distorted square
      pyramidal coordination environments. The molecular structure is stabilized by
      weak C-H?O and N-H?Cl hydrogen bonds. The crystal structure exhibit weak inter
      molecular N-H?O, C-H?O and N-H?Cl inter-actions, generating a three-dimensional
      network. 

PMID- 24454024
TI  - Bis[(5-bromo-pyridin-2-yl)methano-lato-kappa(2) N,O]copper(II) monohydrate.
AB  - In the title compound, [Cu(C6H5BrNO)2].H2O, the Cu(II) ion has a square-planer
      N2O2 coordination environment. Slipped pi-pi stackings [centroid-centroid
      distances: 3.625 (3), 3.767 (3), 3.935 (3) and 4.255 (3) A] between pyridine
      rings and Cu?pi inter-actions (centroid-to-Cu(II) distance: 3.56 A) between
      Cu(2+) ions and pyridine rings lead to a layered arrangement parallel to (010).
      Inter-molecular Br?O inter-actions [Br?O distances: 2.904 (3) and 3.042 (3) A]
      and O-H?O hydrogen bonds form a three-dimensional network structure. 

PMID- 24454025
TI  - catena-Poly[[di-aqua-[MU2-4-(4-carb-oxy-phen-oxy)benzoato](MU2-4,4'-oxydibenzo
      ato)praseodymium(III)] monohydrate].
AB  - In the title compound, {[Pr(C14H8O5)(C14H9O5)(H2O)2].H2O} n , the Pr(III) cation
      is eight-coordinated by six carboxyl O atoms from both a monoanionic 4-(4-carb
      oxy-phen-oxy)benzoate and a dianionic 4,4'-oxydibenzoate ligand (four bridging
      with two from a bidentate chelate inter-action), and two O-atom donors from water
      mol-ecules. A single water mol-ecule of solvation is also present. The complex
      units are linked through carboxyl O:O' bridges giving a two-dimensional sheet
      polymer lying parallel to (001). An overall three-dimensional network structure
      is generated through inter-molecular carb-oxy-lic acid and water O-H?O hydrogen
      bonds and weak C-H?O inter-actions. 

PMID- 24454026
TI  - Di-chlorido-{2-[(E)-phen-yl(pyridin-2-yl-kappaN)methyl-idene]-N-phenyl-hydra-zine
      carboxamide-kappa(2) N (2),O}copper(II).
AB  - The title compound, [CuCl2(C19H16N4O)], contains a Cu(II) atom N,N',O-chelated by
      a neutral N-phenyl-hy-dra-zine-car-box-amide ligand and additionally coordinated
      by two Cl atoms, resulting in a distorted square-pyramidal geometry. The ligating
      atoms in the basal square plane of the complex comprise the azomethine N, the
      pyridine N, the amide O and one of the Cl atoms, whereas the other Cl atom
      occupies an apical position. The apical Cl atoms in adjacent layers function as
      hydrogen-bond acceptors to both NH groups. Intermolecular C-H?Cl and C-H?O
      interactions are also observed. 

PMID- 24454027
TI  - [2,6-Di-fluoro-3-(pyridin-2-yl-kappaN)pyridin-4-yl-kappaC (4)](penta-ne-2,4
      dionato-kappa(2) O,O')iridium(III).
AB  - The title compound, [Ir(C10H5F2N2)2(C5H7O2)], has a distorted octa-hedral
      coordination geometry around the Ir(III) atom, retaining the cis-C,C/trans-N,N
      chelate disposition in two 2,6-di-fluoro-3-(pyridin-2-yl-kappaN)pyridin-4-yl
      ligands which are nearly mutually perpendicular [dihedral angle = 82.75 (15)
      degrees ]. The mol-ecular structure is stabilized by weak C-H?O and C-H?F
      hydrogen-bond inter-actions. The crystal structure is stabilized by pi-pi
      stacking inter-actions (centroid-centroid distance = 3.951 A). 

PMID- 24454028
TI  - Di-MU-acetato-kappa(4) O:O'-bis-[(1,10-phenanthroline-kappa(2) N,N')(tri-fluoro
      methane-sulfonato-kappaO)copper(II)].
AB  - The complete molecule of the title compound, [Cu2(C2H3O2)2(CF3O3S)2(C12H8N2)2],
      is completed by the application of a twofold rotation and comprises two Cu(II)
      ions, each of which is penta-coordinated by two N atoms from a bidentate 1,10
      phenanthroline (phen) ligand, two O atoms from acetate ligands and an O atom from
      a tri-fluoro-methane-sulfonate anion, forming a (4 + 1) distorted square
      pyramidal coordination geometry. The Cu(II) ions are connected by two acetate
      bridges in a syn-syn configuration. The F atoms of the tri-fluoro-methane
      sulfonate ligands are disordered, with site-occupation factors of 70 and 30. The
      molecular structure is stabilized by intra-molecular face-to-face pi-pi inter
      actions with centroid-centroid distances in the range 3.5654 (12)-3.8775(12) A.
      The crystal structure is stabilized by C-H?O interactions, leading to a three
      dimensional lattice structure. 

PMID- 24454029
TI  - catena-Poly[[di-aqua-bis-(MU3-5-carboxyl-ato-1H-pyrazole-3-carb-oxy-lic acid
      kappa(3) O (3):O (3);O (5))dilithium(I)] monohydrate].
AB  - The basic structural unit of the title polymeric ribbon,
      {[Li2(C5H3N2O2)2(H2O)2].H2O} n , is a centrosymmetric dinuclear complex in which
      the two Li(I) ions are bridged by two carboxyl-ato O atoms, to generate a
      centrosymmetric Li2O2 core. These are connected into a chain along [01-1] by
      carboxylic acid-carbonyl-O bonds. The tetra-hedral coordination of the Li(I)
      cation is completed by an aqua ligand. The carboxylic acid is involved in an
      intra-ribbon hydrogen bond. A solvate water molecule showing positional (50:50)
      disorder is observed. Polymeric ribbons along [01-1] are connected by O-H?O, N
      H?O and O-H?N hydrogen bonds into a three-dimensional architecture. 

PMID- 24454030
TI  - Tetra-quinolinium ditelluro(VI)octa-vanadate(V) octa-hydrate.
AB  - In the title compound, (C9H8N)4[Te2V8O28].8H2O, the com-plete heteropolyanion is
      generated by a crystallographic inversion centre. One of the two quniolinium ions
      forms an N-H?Op (p = polyoxidometallate) hydrogen bond and the other an N-H?Ow (w
      = water) hydrogen bond. The water mol-ecules further link the components by O
      H?Op and O-H?Ow hydrogen bonds. A number of C-H?O inter-actions and aromatic pi
      pi stacking inter-actions [shortest centroid-centroid separation = 3.541 (7) A]
      are also observed. Together, these generate a three-dimensional network. 

PMID- 24454031
TI  - catena-Poly[[bis-(nitrato-kappa(2) O,O')barium]-bis-(MU-l-histidine-kappa(3)
      O,O':O].
AB  - In the polymeric title compound, [Ba(NO3)2(C6H9N3O2)2] n , the Ba(II) atom is
      located on a crystallographic twofold axis and is coordinated by ten O atoms. Six
      are derived from two zwitterionic l-histidine mol-ecules that simultaneously
      chelate one Ba(II) atom and bridge to another. The remaining four O atoms are
      derived from two chelating nitrates. The mol-ecules assemble to form a chain
      along [010]. In the crystal, chains are linked via N-H?O and N-H?N hydrogen
      bonds, generating a three-dimensional network. 

PMID- 24454032
TI  - Di-MU-hydroxido-kappa(4) O:O-di-MU-perchlorato-kappa(4) O:O'-bis-[(2,2'-bi
      pyridine-kappa(2) N,N')copper(II)].
AB  - In the title binuclear copper(II) complex, [Cu2(ClO4)2(OH)2(C10H8N2)2], the
      Cu(II) ion is coordinated in the form of a Jahn-Teller distorted octahedron by
      two bi-pyridine N atoms, two perchlorate O atoms and two hydroxide O atoms, and
      displays a distorted octa-hedral geometry. The mol-ecule belongs to the symmetry
      point group C 2h . The Cu(II) ion is located on a twofold rotation axis and the
      hydroxide and perchlorate ligands are located on a mirror plane. Within the
      dinuclear mol-ecule, the Cu?Cu separation is 2.8614 (7) A. The crystal structure
      exhibits O-H?O, C-H?O and pi-pi [centroid-centroid distance = 3.5374 (13) A]
      inter-actions. 

PMID- 24454033
TI  - Tris[4-bromo-2-(methyl-imino-meth-yl)phenolato-kappa(2) N,O]cobalt(III).
AB  - In the title compound, [Co(C8H7BrNO)3], the Co(III) ion is coordinated in a
      slightly distorted octa-hedral environment by three N atoms and three O atoms
      from three bidentate 4-bromo-2-(methyl-imino-meth-yl)phenolate ligands. The
      dihedral angles between the benzene rings are 82.6 (2), 57.1 (2) and 62.9 (2)
      degrees . In the crystal, mol-ecules are linked by pairs of weak C-H?Br hydrogen
      bonds, forming inversion dimers. 

PMID- 24454034
TI  - Hexa-aqua-bis-[3,5-bis-(hy-droxy-imino)-1-methyl-2,4,6-trioxo-cyclo-hexa-nido
      kappa(2) N (3),O (4)]barium tetrahydrate.
AB  - In the title compound, [Ba(C7H5N2O5)2(H2O)6].4H2O, the Ba(2+) cation lies on a
      twofold rotation axis and is ten-coordinated by two 3,5-bis-(hy-droxy-imino)-1
      methyl-2,4,6-trioxo-cyclo-hexa-n-ide oxo O atoms [Ba-O = 2.8715 (17) A], two hy
      droxy-imino N atoms [Ba-N = 3.036 (2) A], and six water mol-ecules [Ba-O = 2.847
      (2), 2.848 (2), and 2.880 (2) A]. The 3,5-bis-(hy-droxy-imino)-1-methyl-2,4,6
      trioxo-cyclo-hexa-nide monoanions act in a bidentate chelating manner,
      coordinating through an N atom of the non-deprotonated hy-droxy-imino group and
      an O atom of the neighboring oxo group. Two lattice water mol-ecules are located
      in the cavities of the framework and are involved in hydrogen bonding to O atoms
      of one of the coordinating water mol-ecules and the O atom of a keto group of the
      ligand. As a result, a three-dimensional network is formed. 

PMID- 24454035
TI  - Bis(MU-di-phenyl-phosphan-yl)bis-[(tri-methyl-phosphane)cobalt(I)](Co-Co).
AB  - The title compound, [Co2{P(C6H5)2}2(C3H9P)4], was obtained by the addition of di
      phenyl-phosphane to a solution of Co(CH3)(C3H9P)4. The dinuclear complex mol
      ecule exhibits inversion symmetry with the inversion centre located between the
      two Co(I) atoms. The short Co-Co distance of 2.3670 (8) A lies within the range
      of metal-metal double bonds. As a result of inversion symmetry, the four-membered
      Co2P2 core is rigorously planar, and the two bridging P(C6H5)2-ligands and the
      terminal C3H9P ligands are arranged in a pseudo-tetra-hedral fashion about the
      Co(I) atom. 

PMID- 24454036
TI  - Ethyl-enedi-ammonium sodium tetra-kis-[bis-(ethyl-enedi-amine-kappa(2)
      N,N')(oxalato-kappa(2) O (1),O (2))cobalt(III)] [penta-hydrogen di(phosphato-octa
      deca-tungstate)] tetra-deca-hydrate.
AB  - The title compound, Na(C2H10N2)[Co(C2O4)(C2H8N2)2]4[H5(P2W18O62)2].14H2O,
      prepared under hydro-thermal conditions, consists of two Dawson-type [P2W18O62](6
      ) anions, four isolated [Co(en)2(ox)](+) cations (en = ethyl-enedi-amine and ox =
      oxalate), one Na(+) cation, one [H2en](2+) cation, and a number of ordered (14)
      and disordered solvent water mol-ecules. The [P2W18O62](6-) polyoxidometalate
      anion has site symmetry 1 and contains two structurally distinct types of W
      atoms: viz. six W atoms on vertical pseudo-mirror planes grouped in two sets of
      three, and 12 equatorial W atoms that do not lie in the pseudo-mirror planes
      grouped in two sets of six. In each [Co(en)2(ox)](+) cation, the Co(III) ion is
      coordinated by four N atoms from two en ligands and two O atoms from the ox
      ligands, completing a distorted octa-hedral structure. The sodium cation lies on
      an inversion centre and additionally links the complex cations and anions. In the
      crystal, the various units are linked by N-H?O and O-H?O hydrogen bonds, which
      together with C-H?O hydrogen bonds form a three-dimensional structure. The
      contribution of a region of disordered electron density, possibly highly
      disordered solvent water mol-ecules, to the scattering was removed with the
      SQUEEZE option of PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]. To
      equilibrate the charges five H(+) ions have been added to the polyoxidometalate.
      These H(+) ions and the disordered solvent contribution were not included in the
      reported mol-ecular weight and density. 

PMID- 24454037
TI  - [1,1'-Bis(di-phenyl-phosphan-yl)cobalto-cenium-kappa(2) P,P'](eta(5)-cyclo-penta
      dien-yl){2-[4-(4-ethynylphen-yl)phen-yl]ethynyl-kappaC}ruthenium(II) hexa
      fluorido-phosphate.
AB  - In the title compound, [CoRu(C5H5)(C16H9)(C17H14P)2]PF6, the Ru(II) atom is
      coordinated by a cyclo-penta-dienyl ring in an eta(5)-mode, one C atom from a
      4,4'-diethynyl-1,1'-biphenyl ligand and two P atoms from a chelating 1,1'-bis-(di
      phenyl-phosphan-yl)cobaltocenium ligand, giving a three-legged piano-stool
      geometry. In the crystal, weak C-H?F hydrogen bonds link the complex cations and
      hexa-fluorido-phosphate anions into a three-dimensional supra-molecular
      structure. 

PMID- 24454038
TI  - catena-Poly[2-methyl-pyridinium [tungstate-di-MU-selenido-silver-di-MU-selenido]
      2-methyl-pyridine monosolvate].
AB  - The title compound, {(C6H8N)[AgWSe4].C6H7N} n , consists of anionic [WAgSe4] n
      chains, 2-methyl-pyridinium cations and neutral 2-methyl-pyridine mol-ecules. The
      Se atoms bridge the Ag and W atoms, forming a polymeric chain extending along the
      b-axis direction. Both the Ag and W atoms are located on a twofold rotation axis
      and each metal atom is coordinated by four Se atoms in distorted tetra-hedral
      geometry. In the crystal, the 2-methyl-pyridinium cation and 2-methyl-pyridine
      mol-ecule are linked via N-H?N hydrogen bonding. Weak C-H?Se inter-actions link
      the organic components and polymeric anions into a three-dimensional
      architecture. 

PMID- 24454039
TI  - (2,2'-Bi-pyridine-kappa(2) N,N')bis-(nitrato-kappa(2) O,O')copper(II).
AB  - In the title complex, [Cu(NO3)2(C10H8N2)], the Cu(II) cation is chelated by two
      nitrate anions and by one 2,2'-bi-pyridine ligand in a distorted N2O4 octa-hedral
      geometry. The dihedral angle between the pyridine rings is 1.92 (11) degrees . In
      the crystal, pi-pi stacking between parallel pyridine rings of adjacent complex
      mol-ecules is observed, the centroid-centroid distance being 3.6788 (19) A. Weak
      C-H?O hydrogen bonds further link the mol-ecules into a three-dimensional supra
      molecular architecture. 

PMID- 24454040
TI  - Bis[4-(di-methyl-amino)-pyridinium] tetra-chlorido-cuprate(II).
AB  - The asymmetric unit of the title salt, (C7H11N2)2[CuCl4], comprises half a
      tetrahedral tetra-chlorido-cuprate anion, being located on a twofold axis, and a
      protonated 4-(di-methyl-amino)-pyridine cation. The geometry around the Cu(II)
      ion is highly distorted with the range of Cl-Cu-Cl angles being 94.94 (1)-141.03
      (1) degrees . The crystal structure is stabilized by N-H?Cl and C-H?Cl hydrogen
      bonds. In the three-dimensional network, cations and anions pack in the lattice
      so as to generate chains of [CuCl4](2-) anions separated by two orientations of
      cation layers, which are inter-locked through pi-pi stacking contacts between
      pairs of pyridine rings, with centroid-centroid distances of 3.7874 (7) A. 

PMID- 24454041
TI  - Rubidium penta-aqua-(l-serine)cobalt(II) hexa-hydrogenhexa-molybdocobaltate(III)
      l-serine monosolvate deca-hydrate.
AB  - The Co(2+) ion in the title compound,
      Rb[Co(C3H7NO3)(H2O)5][H6CoMo6O24].C3H7NO3.10H2O, is coordinated by five water mol
      ecules and one O-monodentate l-serine ligand in a slightly distorted octahedral
      geometry. The Rb(+) ion is irregularly coordinated by nine O atoms. In the
      crystal, the [H6Co(III)Mo6O24](3-) polyanions are stacked along the b-axis
      direction, mediated by bridging Rb-O bonds. N-H?O and O-H?O hydrogen bonds are
      observed involving the l-serine mol-ecules. 

PMID- 24454042
TI  - Bis[(di-methyl-phosphor-yl)methan-amin-ium] tetra-chlorido-palladate(II).
AB  - In the crystal structure of the title compound, (C3H11NOP)2[PdCl4], (di-methyl
      phosphor-yl)methanaminium (dpmaH(+)) cations are connected head-to-tail by strong
      N-H?O hydrogen bonds, forming inversion-related cyclic dimers. The square-planar
      [PdCl4](2-) counter-dianion is located about a center of inversion. The dications
      and the [PdCl4](2-) dianions are connected by medium-strong N-H?Cl hydrogen
      bonds, forming zigzag chains parallel to [001]. Somewhat weaker N-H?Cl hydrogen
      bonds connect the chains into a three-dimensional network. 

PMID- 24454043
TI  - Poly[[(MU2-benzene-1,3-di-carboxyl-ato){MU2-1,4-bis-[(1H-imidazol-1-yl)meth
      yl]benzene}-cadmium] di-methyl-formamide monosolvate].
AB  - The title coordination polymer, {[Cd(C8H4O4)(C14H14N4)].C3H7NO} n , was
      synthesized by solvothermal reaction of metallic cadmium with the semi-rigid
      neutral ligand 1,4-bis-[(1H-imidazol-1-yl)meth-yl]benzene (bix) and the V-shaped
      benzene-1,3-di-carb-oxy-lic acid (m-H2bdc). The structure exhibits a pseudo-C
      centring which is almost fulfilled by the polymeric metal complex but not by the
      solvent dimethylform-amide (DMF) mol-ecules. The asymmetric unit contains two
      independent Cd(II) ions, two m-bdc(2-) ligands, one and two half bix ligands, and
      two solvent DMF mol-ecules. The Cd(II) ions are both five-coordinated by three O
      atoms from two different m-bdc(2-) ligands and two N atoms from two different bix
      ligands in a distorted square-pyramidal geometry. The m-bdc(2-) ligands adopt a
      chelate-monodentate coordination mode, connecting neighboring Cd(II) ions into a
      zigzag chain parallel to [110]. Adjacent chains are further cross-linked by bix
      ligands, giving rise to a puckered sheet nearly perpendicular to the chain
      direction. Thus, each Cd(II) ion is connected to four neighboring Cd(II) ions
      through two m-bdc(2-) anions and two bix ligands, giving rise to the final non
      inter-penetrating uninodal layer with sql (4,4) topology. 

PMID- 24454044
TI  - Hexa-kis-(dimethyl sulfoxide-kappaO)zinc(II) poly-iodide.
AB  - The title compound, [Zn{(CH3)2SO}6]I4, is a one-dimensional supra-molecular
      polymer along a threefold rotation axis of the space group. It is built up from
      discrete [Zn{(CH3)2SO}6](2+) units connected through non-classical hydrogen bonds
      to linear I4 (2-) polyiodide anions (C-H?I = 3.168 A). The Zn(II) ion in the
      cation has an octa-hedral coordination geometry, with all six Zn-O bond lengths
      being equivalent, at 2.111 (4) A. The linear polyiodide anion contains a neutral
      I2 mol-ecule weakly coordinated to two iodide ions. 

PMID- 24454045
TI  - Redetermination of bis-(acetyl-acetonato-kappa(2) O,O')(1,10-phenanthroline
      kappa(2) N,N')manganese(II).
AB  - In the crystal structure of the title compound, [Mn(C5H7O2)2(C12H8N2)], the
      Mn(2+) cation is coordinated by one bidentate 1,10-phenanthroline ligand and two
      acetyl-acetonate anions within a slightly distorted N2O4 octa-hedron. The
      asymmetric unit consists of one Mn(2+) cation situated on a twofold rotation
      axis, one half of a 1,10-phenanthroline ligand and one acetyl-acetonate anion. In
      comparison with the previous determination based on visually estimated
      intensities recorded on precession photographs, the current redetermination with
      image-plate data reveals bond lengths and angles with much higher precision. 

PMID- 24454046
TI  - Di-chlorido-bis-[1-(2,4,6-tri-methyl-phen-yl)-1H-imidazole-kappaN (3)]copper(II).
AB  - In the title complex, [CuCl2(C12H14N2)2], the Cu(2+) cation is situated on an
      inversion centre and is coordinated by two N atoms from symmetry-related 1
      mesityl-1H-imidazole ligands and by two chloride anions in a slightly distorted
      square-planar geometry. In the organic ligand, the dihedral angle between the
      benzene ring of the mesityl moiety and the imidazole ring is 76.99 (18) degrees .
      Weak intra-molecular C-H?Cl hydrogen-bonding inter-actions consolidate the mol
      ecular conformation. 

PMID- 24454047
TI  - catena-Poly[bis-[dimeth-yl(pyridine-kappaN)indium(III)]-MU4-benzene-1,3-diolato
      bis-[di-methyl-indium(III)]-MU4-benzene-1,3-diolato].
AB  - The title compound, [In2(CH3)4(C6H4O2)(C5H5N)] or [{(CH3)2In}(1,3
      O2C6H4){In(CH3)2(py)}] n , (py = pyridine) contains two crystallographically
      unique In(III) ions which are in distorted tetra-hedral C2O2 and distorted
      trigonal-bipyramidal C2O2N coordination environments. The In(III) coordination
      centers are bridged head-to-head via In-O bonds, yielding four-membered In2O2
      rings and zigzag polymeric chains along [001]. 

PMID- 24454048
TI  - Di-MU-iodido-bis-(iodido-{methyl 4-[(pyridin-2-yl-methyl-idene)amino]-benzoate
      kappa(2) N,N'}cadmium).
AB  - The complete binuclear molecule of the title compound, [Cd2I4(C14H12N2O2)2], is
      generated by the application of a centre of inversion. The Cd-I bond lengths of
      the central core are close and uniformly longer than the exocyclic Cd-I bond. The
      coordination sphere of the Cd(II) atom is completed by two N atoms of a chelating
      methyl 4-[(pyridin-2-yl-methyl-idene)amino]-benzoate ligand, and is based on a
      square pyramid with the terminal I atom in the apical position. The three
      dimensional crystal packing is stabilized by C-H?O and C-H?pi inter-actions, each
      involving the pyridine ring. 

PMID- 24454049
TI  - Bis(MU-hydroxido-kappa(2) O:O)bis[bis(5-car-boxy-pyridine-2-carboxyl-ato-kappa(2)
      N,O (2))iron(III)] dihydrate.
AB  - The complete binuclear complex in [Fe2(C7H4NO4)4(OH)2].2H2O, is generated by the
      application twofold symmetry. The Fe(III) atom is coordinated by the O atoms of
      two bridging hydroxyl groups and by two N and two O atoms from two pyridine-2,5
      di-carboxyl-ato ligands, forming a distorted octa-hedral geometry. The Fe?Fe
      separation within the dinuclear complex is 3.0657 (4) A. In the crystal, O-H?O
      and C-H?O hydrogen-bonding inter-actions connect the mol-ecules into a three
      dimensional supra-molecular network. 

PMID- 24454050
TI  - Di-MU-oxido-bis-({2,2'-[ethane-1,2-diylbis(nitrilo-methanylyl
      idene)]diphenolato}titanium(IV)) chloro-form disolvate.
AB  - In the title compound, [Ti2(C16H14N2O2)2O2].2CHCl3, the Ti(IV) atom in the
      centrosymmetric complex has a distorted octa-hedral N2O4 coordination environment
      and is linked via two MU2-oxido bridges into a dinuclear centrosymmetric com
      plex, with a Ti?Ti separation of 2.7794 (8) A. In the salen (N,N'-ethyl
      enebis(salicyl-imine)) ligand, the two salicyl-imine units make a dihedral angle
      of 45.31 (5) degrees . The complex mol-ecules are stacked parallel to [100],
      forming channels in which the solvent chloro-form mol-ecules are located. C-H?O
      hydrogen-bonding inter-actions between the complex mol-ecules and the solvent mol
      ecules consolidate the crystal packing. 

PMID- 24454051
TI  - Anthracene-1,4,9,10-tetra-one.
AB  - The asymmetric unit of the title compound, C14H6O4, contains three independent
      mol-ecules (A, B and C). In mol-ecule C, there are two disordered sets of two
      carbonyl O atoms [occupancies = 0.643 (11) and 0.357 (11)]. All three mol-ecules
      are non-planar due to repulsion between two O atoms in peri positions on the
      anthracene ring, showing a slight difference in deviation of the carbonyl O
      atoms. The intra-molecular distances between the two nearest O atoms are in the
      range of 2.685 (10)-2.766 (10) A. In the crystal, mol-ecules are linked by C-H?O
      and pi-pi [centroid-centroid distances = 3.615 (2), 3.844 (2) and 3.921 (2) A]
      inter-actions, which lead to the formation of a herringbone-like arrangement. 

PMID- 24454052
TI  - 3-Isopropyl-1-{2-[(1-methyl-1H-tetra-zol-5-yl)sulfan-yl]acet-yl}-2,6-di-phenyl
      piperidin-4-one hemihydrate.
AB  - In the title compound, C24H27N5O2S.0.5H2O, the piperidine ring adopts a distorted
      boat conformation. The phenyl rings subtend dihedral angles of 69.7 (1) and 88.7
      (1) degrees  with the best plane through the piperidine moiety. In the crystal,
      symmetry-related mol-ecules are linked through a network of C-H?O and C-H?N inter
      actions, the former connecting them into zigzag chains along the c-axis direction
      and the latter forming an R (2) 2(4)motif. The dimer formation (C-H?N) and the
      repetition of symmetry-related molecules (C-H?O) along the b-axis direction
      stabilize the packing mode. The water mol-ecule is located on a twofold rotation
      axis. 

PMID- 24454053
TI  - 2-(2,4-Di-fluoro-phen-yl)-4,5-dimethyl-1-(4-methyl-phen-yl)-1H-imidazole
      monohydrate.
AB  - The asymmetric unit of the title compound, C18H16F2N2.H2O, contains two
      independent mol-ecules (A and B), and two independent water mol-ecules of
      crystallization. In mol-ecule A, the imidazole ring makes dihedral angles of
      47.46 (7) and 60.98 (6) degrees  with the 2,4-di-fluoro-phenyl and methyl-phenyl
      rings, respectively. The corresponding angles in mol-ecule B are 45.85 (7) and
      62.78 (7) degrees , respectively. The dihedral angle between the two benzene
      rings is 64.98 (7) degrees  in mol-ecule A and 65.53 (7) degrees  in mol-ecule B.
      In the crystal, the two independent mol-ecules are linked by O-H?N and O-H?O
      hydrogen bonds, forming chains propagating along [100]. These chains are linked
      via C-H?F hydrogen bonds, forming slab-like two-dimensional networks lying
      parallel to (001). 

PMID- 24454054
TI  - (1S,1'S,2'R,4a'S,9a'S,9b'R)-1'-Acet-yloxy-2,4'-dioxo-2',4',4a',7',8',9',9a',9b'
      octa-hydro-1'H,2H-spiro-[ace-naphthyl-ene-1,5'-pyrano[4,3-a]pyrrolizin]-2'
      ylmethyl acetate.
AB  - In the title compound C26H25NO7, the mean plane through the lactone-substituted
      ring of the pyrrolizidine moiety forms dihedral angles of 78.46 (6) and 58.28 (8)
      degrees  with the ace-naphthyl-ene moiety and the sugar based-lactone ring,
      respectively. The sum of the angles at the the N atom of the pyrrolizidine ring
      (335.0 degrees ) is in accordance with sp (3) hybridization. Some atoms of the
      acetate group are disordered and were refined using a split model [occupancy
      ratio 0.673 (10):0.327 (10)]. 

PMID- 24454055
TI  - N-(4-Fluoro-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.
AB  - In the title compound, C12H16FNO2, the dioxane ring adopts a chair conformation
      with the methyl substituents and the C-N bond in equatorial orientations. Its
      mean plane subtends a dihedral angle of 40.17 (6) degrees  with the benzene ring.
      In the crystal, weak N-H?F hydrogen bonds link the mol-ecules into C(7) chains
      propagating in [100]. 

PMID- 24454056
TI  - 2-Allyl-7-nitro-2H-indazole.
AB  - The asymmetric unit of the title compound, C10H9N3O2, contains two independent
      mol-ecules linked by a C-H?N hydrogen bond. Each mol-ecule has a similar
      conformation, being built up from fused five- and six-membered rings, each linked
      to an ally and nitro group, respectively. The indazole ring system makes dihedral
      angles of 2.7 (2) and 2.2 (2) degrees , respectively, with the plane through the
      nitro group. The allyl group is nearly perpendicular to the indazole system, as
      indicated by the N-N-C-C torsion angles of -75.3 (2) and -82.2 (2) degrees , this
      being the most important difference between the conformations of the two mol
      ecules. In the crystal, mol-ecules are linked by C-H?O and pi-pi [inter-centroid
      distance = 3.6225 (8) A] inter-actions to form a three-dimensional network. 

PMID- 24454057
TI  - 1H-Benzotriazole-4-hy-droxy-benzoic acid (1/1).
AB  - The asymmetric unit of the title compound, C6H5N3.C7H6O3, comprises independent
      benzotriazole and 4-hydroxybenzoic acid molecules. The dihedral angle between the
      benzene ring and the benzotriazole ring system is 15.18 (7) degrees . The mean
      plane of the carb-oxyl group is twisted at an angle of 18.55 (1) degrees  with
      respect to the benzene ring. The crystal structure is stabilized by weak inter
      molecular N-H?N, O-H?N, O-H?O and C-H?O inter-actions, forming a three
      dimensional network. 

PMID- 24454058
TI  - 4-[2-(Pyridin-1-ium-4-yl)eth-yl]pyridin-1-ium bis-(2,6-di-nitro-benzoate).
AB  - The asymmetric unit of the title salt, C12H14N2 (2+).2C7H3N2O6 (-), comprises
      half a 4-[2-(pyridin-1-ium-4-yl)eth-yl]pyridin-1-ium dication, being disposed
      about a centre of inversion, and a 2,6-di-nitro-benzoate anion, in a general
      position. In the anion, the carboxyl-ate group is inclined to the benzene ring
      [dihedral angle = 85.45 (9) degrees ], whereas near-coplanar and twisted
      arrangements are found for the nitro groups [O-N-C-C torsion angles = 179.80 (14)
      and 20.2 (2) degrees ]. In the crystal, three-component aggregates sustained by
      charge-assisted N(+)-H?O(-) hydrogen bonds are found and these are consolidated
      into a three-dimensional architecture by C-H?O and pi-pi [inter-centroid
      distances = 3.6796 (14) and 3.7064 (14) A] inter-actions. 

PMID- 24454059
TI  - Dimethyl 4,4'-(diazenedi-yl)dibenzoate at 100 K.
AB  - In the asymmetric part of the unit cell of the title compound, C16H14N2O4, there
      are two chemically equivalent but crystallographic independent half mol-ecules.
      The geometric centre of each complete mol-ecule lies on a crystallographic
      inversion centre. Both mol-ecules are almost planar [mean deviations of atoms in
      the two molecules are 0.032 (2) and 0.044 (2) A] and their geometries are
      similar. In the crystal, mol-ecules are arranged in columns along the a axis.
      There are no inter-molecular donor-acceptor distances shorter than 3.4 A. 

PMID- 24454060
TI  - 4-Nitro-anilinium 3-carb-oxy-4-hy-droxy-benzene-sulfonate monohydrate.
AB  - In the title hydrated salt, C6H7N2O2 (+).C7H5O6S(-).H2O, the benzene ring of the
      cation makes a dihedral angle of 1.32 (19) degrees  with the attached nitro
      group. In the anion, an intra-molecular O-H?O hydrogen bond with an S(6) ring
      motif is formed between the carb-oxyl and hy-droxy groups; the dihedral angle
      between the carb-oxyl group and the benzene ring is 8.76 (8) degrees . The
      crystal structure exhibits inter-molecular N-H?O, O-H?O, C-H?O, and pi-pi
      [centroid-centroid distances = 3.6634 (9) and 3.7426 (9) A] inter-actions to form
      a three-dimensional network. 

PMID- 24454061
TI  - Ethyl (2E)-2-cyano-3-(4-meth-oxy-phen-yl)acrylate.
AB  - In the title compound, C13H13NO3, the conformation across the C=C bond is
      synperiplanar, the torsion angle of the segment C(ring)-C=C-C(N) being 3.2 (5)
      degrees . In the crystal, mol-ecules are linked into inversion dimers, arranged
      in a zigzag pattern, through two C-H?O inter-actions generating R 2 (2)(10) and R
      2 (2)(14) motifs. These dimers are arranged in a zigzag pattern in the crystal
      structure. The mol-ecules are further linked along the c axis through weak C-H?pi
      inter-actions, and weak pi?pi inter-actions [centroid-centroid separation =
      3.9986 (17) A] are also observed. 

PMID- 24454062
TI  - 1-(5,5-Di-meth-oxy-pent-yl)-3-methyl-imidazolium-2-carboxyl-ate.
AB  - The title compound, C12H20N2O4, represents one example of a zwitterionic
      imidazolium salt with a carboxyl-ate group at the 2-position of the imidazolium
      ring. The dihedral angle between the heterocyclic ring and the carboxyl-ate group
      is 31.3 (1) degrees . The side chain linking the N atom of the ring and the
      methine C atom has a gauche-anti-anti conformation [torsion angles = -60.3 (2), 
      175.7 (2) and 178.7 (2) degrees , respectively]. In the crystal, mol-ecules are
      linked by short C-H?O hydrogen bonds involving the C-H groups in the aromatic
      ring to generate (001) sheets. 

PMID- 24454063
TI  - S,S'-Butane-1,4-diyl bis-(benzene-carbo-thio-ate).
AB  - The title compound, C18H18O2S2, which lies on an inversion center, adopts a
      gauche (+)-trans-trans-trans-gauche (-) (g (+) tttg (-)) conformation in the S
      CH2-CH2-CH2-CH2-S bond sequence. In the crystal, mol-ecules are packed in a
      herringbone arrangement through inter-molecular C-H?pi inter-actions. 

PMID- 24454064
TI  - 2,3-Bis(furan-2-yl)pyrazino-[2,3-f][1,10]phenanthroline.
AB  - The mol-ecule of the title compound, C22H12N4O2, is located on a twofold rotation
      axis. The dihedral angle between the furan and pyrazine rings is 34.8 (7) degrees
      , and that between the furan rings is 46.92 (7) degrees . A pi-pi stacking
      interaction occurs between adjacent pyrazino[2,3-f][1,10]phenanthroline units,
      with an interplanar distance of 3.5862 (12) A. 

PMID- 24454065
TI  - N'-[(E)-Benzyl-idene]-2-(6-meth-oxy-naphthalen-2-yl)propano-hydrazide.
AB  - The title mol-ecule, C21H20N2O2, exists in the solid state in the 'extended'
      form. The crystal packing consists of ribbons of mol-ecules extending parallel to
      c and associated via N-H?O and weak C-H?O hydrogen bonds. C-H?pi inter-actions
      are also present. 

PMID- 24454066
TI  - 4-Amino-N-(4,6-di-methyl-pyrimidin-2-yl)benzene-sulfonamide-1,4-di-aza-bicyclo
      [2.2.2]octane (2/1).
AB  - The asymmetric unit of the title co-crystal, C12H14N4O2S.0.5C6H12N2, comprises
      the sulfonamide mol-ecule and half a mol-ecule of 1,4-di-aza-bicyclo
      [2.2.2]octane (DABCO), the latter being disposed about a crystallographic twofold
      rotation axis. In the sulfonamide mol-ecule, the aromatic rings are almost
      perpendicular to one another [dihedral angle = 75.01 (8) degrees ]. In the
      crystal, mol-ecules are connected into a three-mol-ecule aggregate via amide
      DABCO N-H?N hydrogen bonds, and these are connected into a three-dimensional
      architecture via amino-DABCO N-H?O and amino-pyrimidine N-H?N hydrogen bonds. 

PMID- 24454067
TI  - 2-Amino-benzoic acid-4-[2-(pyridin-4-yl)eth-yl]pyridine (2/1).
AB  - The asymmetric unit of the title co-crystal, C12H12N2.2C7H7NO2, comprises a
      centrosymmetric 4-[2-(pyridin-4-yl)eth-yl]pyridine mol-ecule and a 2-amino
      benzoic acid mol-ecule in a general position. The acid has a small twist between
      the carb-oxy-lic acid residue and the ring [dihedral angle = 7.13 (6) degrees ]
      despite the presence of an intra-molecular N-H?O(carbon-yl) hydrogen bond. Three
      mol-ecule aggregates are formed via O-H?N(pyrid-yl) hydrogen bonds, and these are
      connected into supra-molecular layers in the bc plane by N-H?O(carbon-yl)
      hydrogen bonds and pi-pi inter-actions between pyridine and benzene rings [inter
      centroid distance = 3.6332 (9) A]. Layers are connected along the a axis by weak
      pi-pi inter-actions between benzene rings [3.9577 (10) A]. 

PMID- 24454068
TI  - N-[2-(2,2-Di-methyl-propanamido)-pyrimidin-4-yl]-2,2-di-methyl-propanamide n
      hexane 0.25-solvate hemihydrate.
AB  - The asymmetric unit of the title compound, C14H22N4O2.0.25C6H14.0.5H2O, contains
      two independent mol-ecules of 2,4-bis-(pivaloyl-amino)-pyrimidine (M) with
      similar conformations, one water mol-ecule and one-half n-hexane solvent mol
      ecule situated on an inversion center. In one independent M mol-ecule, one of the
      two tert-butyl groups is rotationally disordered between two orientations in a
      3:2 ratio. The n-hexane solvent mol-ecule is disordered between two conformations
      in the same ratio. The water mol-ecule bridges two independent M mol-ecules via O
      H?O, N-H?O and O-H?N hydrogen bonds into a 2M.H2O unit, and these units are
      further linked by N-H?N hydrogen bonds into chains running in the [010]
      direction. Weak C-H?O inter-actions are observed between the adjacent chains. 

PMID- 24454069
TI  - 8-Meth-oxy-3-methyl-3,4-di-hydro-2H-1,3-benzoxazine.
AB  - The title compound, C10H13NO2, crystallizes with two crystallographically
      independent mol-ecules of similar geometry in the asymmetric unit; the six
      membered oxazine rings adopts a half-chair conformation. Neither hydrogen bonds
      nor pi-pi inter-actions are observed in the crystal structure. 

PMID- 24454070
TI  - 3,14-Diethyl-2,13-di-aza-6,17-diazonia-tri-cyclo-[16.4.0.0(7,12)]docosane
      dichloride tetra-hydrate from synchrotron radiation.
AB  - The asymmetric unit of title hydrated salt, C22H46N4 (2+).2Cl(-).4H2O, comprises
      half a centrosymmetric dication, one Cl(-) anion and two water mol-ecules of
      crystallization. The structure determination reveals that protonation has
      occurred at diagonally opposite amine N atoms, and that the dication features
      intra-molecular N-H?N hydrogen bonds. In the crystal, a three-dimensional
      artchitecture is formed by O-H?Cl/N and N-H?Cl/O hydrogen bonds. 

PMID- 24454071
TI  - tert-Butyl 2-(6-{2-[2-(4-fluoro-phen-yl)-5-isopropyl-3-phenyl-4-(phenyl-carbamo
      yl)pyrrol-1-yl]eth-yl}-2,2-dimethyl-1,3-dioxan-4-yl)acetate.
AB  - The title compound, C40H47FN2O5, crystallizes with two independent but similar
      mol-ecules in the asymmetric unit. In the crystal, mol-ecules are linked into
      chains along [100] by inter-molecular N-H?O hydrogen bonds. 

PMID- 24454072
TI  - N-(1,3-Benzo-thia-zol-2-yl)acetamide.
AB  - The title compound, C9H8N2OS, crystallizes with two mol-ecules (A and B) in the
      asymmetric unit. The dihedral angles between the mean planes of the 1,3-benzo
      thia-zol-2-yl ring system and the acetamide group are 2.7 (4) (mol-ecule A) and
      7.2 (2) A (mol-ecule B). In the crystal, pairs of N-H?N hydrogen bonds link the A
      and B mol-ecules into dimers, generating R 2 (2)(8) loops. The dimers stack along
      [100]. 

PMID- 24454073
TI  - 1-Methyl-4-[(E)-2-(3-hy-droxy-4-meth-oxy-phen-yl)ethen-yl]pyridinium 4-bromo
      benzene-sulfonate monohydrate.
AB  - In the title hydrated salt, C15H16NO2 (+).C6H4BrO3S(-).H2O, the cation exists in
      an E conformation with respect to the ethenyl bond and is almost planar, with a
      dihedral angle of 2.62 (12) degrees  between the planes of the pyridinium and
      benzene rings. The meth-oxy substituent deviates slightly from the plane of its
      attached benzene ring [Cmeth-yl-O-C-C torsion angle = -11.6 (6) degrees ]. In the
      crystal, the cations, anion and water mol-ecules are linked together into chains
      along [010] by O-H?O hydrogen bonds and weak C-H?O inter-actions. There is a
      short Br?O contact [3.029 (2) A]. The crystal structure also features C-H?pi
      inter-actions involving the benzene ring of the anion. 

PMID- 24454074
TI  - 4-[(4-Methyl-phen-yl)sulfan-yl]butan-2-one.
AB  - In the title compound, C11H14OS, all non-H atoms are essentially coplanar, with a
      mean deviation of 0.023 A. In the crystal, centrosymmetrically related mol-ecules
      are weakly connected into dimers by pairs of C-H?O inter-actions. The dimers are
      further linked along the a axis by weak C-H?pi and C-H?S inter-actions. 

PMID- 24454075
TI  - 2,2'-Bis{8-[(benzyl-amino)-methyl-idene]-1,6-dihy-droxy-5-isopropyl-3-methyl
      naphthalen-7(8H)-one}.
AB  - The asymmetric unit of the title compound, C44H44N2O6, contains two independent
      mol-ecules with similar conformations. The di-hydro-naphthalene ring systems are
      approximately planar [maximum deviations = 0.036 (2), 0.128 (2), 0.0.24 (2) and
      0.075 (2) A]. The dihedral angle between two di-hydro-naphthalene ring systems is
      83.37 (4) degrees  in one mol-ecule and 88.99 (4) degrees  in the other. The
      carbonyl O atom is linked with the adjacent hy-droxy and imino groups via intra
      molecular O-H?O and N-H?O hydrogen bonds. In the crystal, mol-ecules are linked
      through O-H?O hydrogen bonds into layers parallel to (001), and adjacent layers
      are further stacked by pi-pi inter-actions between di-hydro-naphthalene and
      phenyl rings into a three-dimensional supra-molecular architecture. In the
      crystal, one of the isopropyl groups is disordered over two positions with an
      occupancy ratio of 0.684 (8):0.316 (8). 

PMID- 24454076
TI  - (3aR,6S,7aR)-7a-Chloro-6-methyl-2-(4-nitro-phenyl-sulfon-yl)-1,2,3,6,7,7a-hexa
      hydro-3a,6-ep-oxy-iso-indole.
AB  - In the title compound, C15H15ClN2O5S, the tetra-hydro-furan ring adopts an
      envelope conformation with the O atom as the flap. The pyrrolidine ring adopts an
      envelope conformation with the chlorine-substituted C atom as the flap. In the
      crystal, two types of C-H?O hydrogen bonds generate R (2) 2(20) and R (4) 4(26)
      rings, with adjacent rings running parallel to ac plane. Further C-H?O hydrogen
      bonds form a C(6) chain, linking the mol-ecules in the b-axis direction. 

PMID- 24454077
TI  - 6-(3,5-Dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetra-zin-3(2H)-one.
AB  - The title compound, C7H8N6O, represents the keto form and adopts a nearly planar
      structure (r.m.s. deviation of the non-H atoms = 0.072 A). In the crystal, mol
      ecules form spiral chains along the c axis by N-H?N hydrogen bonds. The chains
      are linked to each other by weak C-H?O hydrogen bonds, forming a three
      dimensional framework. 

PMID- 24454078
TI  - N-(3-Chloro-1H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.
AB  - In the title compound, C14H12ClN3O3S, the fused five- and six-membered rings are
      folded slightly along the common edge, forming a dihedral angle of 3.2 (1)
      degrees . The mean plane through the indazole system makes a dihedral angle of
      30.75 (7) degrees  with the distant benzene ring. In the crystal, N-H?O hydrogen
      bonds link the mol-ecules, forming a two-dimensional network parallel to (001). 

PMID- 24454079
TI  - 4,4'-Oxybis(2,6-di-methyl-pyridinium) bis-(tri-fluoro-methane-sulfonate).
AB  - In the asymmetric unit of the title salt, C14H18N2O(2+).2CF3O3S(-), the
      components are linked by two N-H?O and one C-H?O hydrogen bonds. The dipyridinium
      salt demonstrates a skew conformation based upon C-O-C-C torsion angles of 61.5
      (3) and 15.1 (4) degrees . A C-O-C angle of 119.3 (2) degrees  and C-O bond
      distances of 1.364 (3) and 1.389 (3) A are consistent with other dipyridyl
      ethers. The planes of the pyridyl rings exhibit a twist angle of 67.89 (8)
      degrees . One of the tri-fluoro-methane-sulfonate ions shows disorder of the F
      atoms [in a 0.52 (7):0.48 (7) occupancy ratio] and an O atom [0.64 (8):0.36 (8)
      occupancy ratio]. In the crystal, the components are linked by C-H?O inter
      actions, which form chains along [101]. 

PMID- 24454080
TI  - N'-[(E)-3-Bromo-benzyl-idene]pyrazine-2-carbohydrazide.
AB  - In the title compound, C12H9BrN4O, the dihedral angle between the aromatic rings
      is 12.16 (12) degrees . An intra-molecular N-H?N hydrogen bond closes an S(5)
      ring. In the crystal, C-H?O hydrogen bonds link the mol-ecules into C(6) chains
      propagating in [010]. Very weak aromatic pi-pi stacking [centroid-centroid
      separations = 3.9189 (15) and 3.9357 (15) A] is also observed. 

PMID- 24454081
TI  - Butane-1,4-diyl bis-(benzene-carbodi-thio-ate).
AB  - The title compound, C18H18S4, which lies on an inversion center, adopts a trans
      gauche (+)-trans-gauche (-)-trans (tg (+) tg (-) t) conformation of the S-CH2-CH2
      CH2-CH2-S bond sequence. In the crystal, a pi-pi inter-action with a centroid
      centroid distance of 3.8797 (16) A is observed. 

PMID- 24454082
TI  - 2,15-Dioxa-7,18,19,20,23-penta-aza-hepta-cyclo
      [21.6.1.1(17,20).0(1,8).0(3,7).0(9,14).0(24,29)]hentriaconta
      9,11,13,17(31),18,24,26,28-octaen-30-one.
AB  - In the title compound, C24H23N5O3, the oxindole ring system is nearly planar,
      with a dihedral angle between the two fused rings of 3.3 (1) degrees . In the
      fused pyrrolo-oxazole ring system, the oxazole and pyrrolidine rings adopt
      envelope conformations with the spiro C atom and one of the methyl-ene C atoms,
      respectively, as the flap atoms. In the crystal, mol-ecules are linked into a
      helical chain along the b axis via C-H?O inter-actions generating R 2 (1)(7) and
      R 2 (2)(8) ring motifs. 

PMID- 24454083
TI  - 4-Di-chloro-methyl-4-methyl-5-(nitro-meth-yl)cyclo-hex-2-enone.
AB  - In the title compound, C9H11Cl2NO3, the six-membered ring adopts a screw-chair
      conformation. In the crystal, two different C-H?O hydrogen bonds involving the
      same acceptor atom connect the mol-ecules into a chain extending along the c-axis
      direction. 

PMID- 24454084
TI  - (Di-methyl-phosphor-yl)methanaminium nitrate.
AB  - In the crystal of the title salt, C3H11NOP(+).NO3 (-), dicationic inversion
      dimers are head-to-tail connected by a pair of strong N-H?O hydrogen bonds. The
      resulting graph-set descriptor of this ring system is R 2 (2)(10). The nitrate
      counter-anions connect the dicationic dimers via N-H?O hydrogen bonds, forming
      two-dimensional networks in the bc plane. 

PMID- 24454085
TI  - (5Z,7Z,9Z)-5,10-Di-bromo-benzo[8]annulene.
AB  - In the structure of the title compound, C12H8Br2, the two bromine substituents
      are oriented exo to the boat-shaped cyclo-octa-tetra-ene at the two ring sites
      that are beta to the ring fusion positions. The average Br-C bond distance is
      1.919 (2) A, the average distance for C=C double bonds that are Br substituted is
      1.328 (2) A, while the other two double-bond distances are 1.327 (2) and 1.398
      (2) A for the non-fused and fused bonds, respectively. Each type of ring inter
      atomic distance is within s.u. of the average values for the four known
      structures, including the title compound, of benzo-fused cyclo-ocata-tetra-enes
      that are not coordinated to a metal atom. The crystal structure features short
      Br?Br [3.6620 (3) A] and C?H [2.834 (2) and 2.841 (2) A] contacts. 

PMID- 24454086
TI  - 2-Amino-6-chloro-N-methyl-benzamide.
AB  - In the title compound, C8H9ClN2O, the dihedral angle between the benzene ring and
      the methyl-amide substituent is 68.39 (11) degrees . In the crystal, mol-ecules
      are linked by N-H?O hydrogen bonds, forming layers parallel to the ab plane. 

PMID- 24454087
TI  - N,N'-Bis(2-amino-benz-yl)ethane-1,2-diaminium dinitrate.
AB  - In the title salt, C16H24N4 (2+).2NO3 (-), both the cation and anion are placed
      in general positions, although the cation displays non-crystallographic inversion
      symmetry, with the aliphatic chain extended in an all-trans conformation. The
      benzene rings are almost parallel, with a dihedral angle between their mean
      planes of 3.3 (6) degrees . The nitrate ions are placed in the vicinity of the
      protonated amine groups, forming efficient N-H?O inter-ion hydrogen bonds. Each
      nitrate ion in the asymmetric unit bridges two symmetry-related cations, forming
      an R 4 (4)(18) ring, a common motif in organic ammonium nitrate salts. This
      results in the formation of chains along [010] with alternating cations and
      anions. The neutral amine groups are involved in slightly weaker N-H?O hydrogen
      bonds with the nitrate O atoms, and there are also a number of C-H?O hydrogen
      bonds present. The resulting supra-molecular structure is based on a two
      dimensional network extending in the ab plane. 

PMID- 24454088
TI  - 5,6-Dimethyl-1H-benzimidazol-3-ium nitrate.
AB  - The title salt, C9H11N2 (+).NO3 (-), features a planar cation (r.m.s. for 11 non
      H atoms = 0.016 A). In the crystal, N-H?O hydrogen bonds link nitrate and
      benzimidazole ions into a three-dimensional network. 

PMID- 24454089
TI  - (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo-[2,3-d]pyrimidin-7-yl)-5-methyl-tetra
      hydro-furan-3,4-diol.
AB  - The mol-ecular structure of the title compound, C11H13IN4O3, shows a ribo-furanos
      yl-pyrrolo O-C-N-C torsion angle of 59.1 (3) degrees , with the central C-N bond
      length being 1.446 (3) A. The C-I bond length is 2.072 (2) A. The amino group is
      coplanar with the attached aromatic ring [C-N-C-N torsion angle = -178.8 (2)
      degrees ] and forms an intra-molecular N-H?I hydrogen bond. In the crystal, O-H?N
      and N-H?O hydrogen bonds link the mol-ecules into puckered layers parallel to
      (001). These layers are bound to each other by secondary I?O inter-actions
      [3.2250 (17) A], forming a three-dimensional framework. 

PMID- 24454090
TI  - 3-Methyl-4-(2-phenyl-1,2,4-triazolo[1,5-a]pyrimidin-7-yl)furazan.
AB  - In the title mol-ecule, C14H10N6O, the planes of the methyl-furazan fragment and
      the phenyl ring attached to the triazolo-pyrimidine bicycle are twisted from the
      mean plane of the bicycle at angles of 45.92 (5) and 5.45 (4) degrees ,
      respectively. In the crystal, pi-pi inter-actions, indicated by short distances
      [in the range 3.456 (3)-3.591 (3) A] between the centroids of the five- and six
      membered rings of neighbouring mol-ecules, link the mol-ecules into stacks
      propagating along the c-axis direction. 

PMID- 24454091
TI  - 4-Benzyl-sulfanyl-1H-pyrazolo-[3,4-d]pyrimidine.
AB  - The pyrazolo-[3,4-d]pyrimidine ring system of the title compound, C12H10N4S, is
      essentially planar [maximum deviation = 0.025 (1) A for the C atom bearing the S
      atom] and almost perpendicular to the phenyl ring [dihedral angle = 71.42 (6)
      degrees ]. In the crystal, mol-ecules are linked via pairs of N-H?N hydrogen
      bonds, forming inversion dimers. 

PMID- 24454092
TI  - (E)-2-[2-(3-Nitro-phen-yl)ethen-yl]quinolin-8-ol.
AB  - In the title compound, C17H12N2O3, the mean planes of the benzene ring and the
      quinoline moiety are inclined to one another by 11.0 (1) degrees . The nitro
      substituent is twisted at an angle of 7.9 (2) degrees  with respect to the
      attached benzene ring. Intra-molecular O-H?N and C-H?N hydrogen bonds occur. The
      crystal is constructed of mol-ecular stacks without involvement of pi-stacking
      inter-actions, but showing inter-stack association via O-H?O and C-H?O hydrogen
      bonding. Thus, the supramolecular architecture of the crystal results from
      stacked molecules stabilized by hydrogen bonding between the stacks. 

PMID- 24454093
TI  - 2-(4-Chloro-phen-yl)-4-phenyl-1,2-di-hydro-quinazoline.
AB  - In the title compound, C20H15ClN2, the pyrimidine ring is in a flattened half
      chair conformation. The phenyl and chloro-substituted benzene rings form dihedral
      angles of 84.97 (5) and 80.23 (4) degrees , respectively, with the benzene ring
      of the di-hydro-quinazoline group. The dihedral angle between the phenyl and
      chloro-substituted benzene rings is 61.71 (5) degrees . In the crystal, mol
      ecules are arranged in inter-secting layers parallel to (101) and (-102), with N
      H?N hydrogen bonds linking mol-ecules along [010]. In addition, a weak C-H?pi
      inter-action is observed. 

PMID- 24454094
TI  - 1,5-Di-meth-oxy-naphthalene.
AB  - The title compound, C12H12O2, lies across an inversion centre. The mol-ecular
      structure suggests that the meth-oxy groups in the 1- and 5-positions of the
      naphthalene moiety do not significantly distort the planar conformation of the
      ring system, which has a maximum deviation of 0.0025 (9) A. In the crystal, mol
      ecules pack in a herringbone arrangement in layers parallel to (100) and with
      chains propagating along [101] formed by very weak C-H?O inter-actions. 

PMID- 24454095
TI  - (6S*)-6-[(1S*,2R*)-1,2-Di-hydroxy-pent-yl]-4-meth-oxy-5,6-di-hydro-2H-pyran-2
      one.
AB  - The title compound, C11H18O5, was isolated from a liquid culture of
      Pestalotiopsis sp. In the mol-ecule, the pyran-2-one ring assumes a half-chair
      conformation. The two terminal C atoms of the pentyl group were refined as
      disordered over two sets of sites, with refined occupancies of 0.881 (10) and
      0.119 (10). In the crystal, mol-ecules are linked via O-H?O hydrogen bonds
      forming a three-dimensional network. 

PMID- 24454096
TI  - 6,7-Diphenyl-5-thia-7-aza-spiro-[2.6]nonan-8-one.
AB  - The asymmetric unit of the title compound, C19H19NOS, contains two independent
      mol-ecules (A and B), in both of which the 1,3-thia-zepan-4-one ring adopts a
      chair-type conformation. The dihedral angles between the two phenyl rings are
      65.28 (8) and 60.31 (9) degrees  for mol-ecules A and B, respectively. In the
      crystal, mol-ecules are linked by weak C-H?O inter-actions, resulting in a three
      dimensional network. 

PMID- 24454097
TI  - N'-[(E)-4-Meth-oxy-benzyl-idene]-2-(5-meth-oxy-2-methyl-1H-indol-3
      yl)acetohydrazide.
AB  - The conformation adopted by the title compound, C20H21N3O3, in the crystal is 'J'
      shaped and appears to be at least partially directed by a weak intra-molecular C
      H?N hydrogen bond. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds,
      forming dimers with R 2 (2)(8) motifs. Furthermore, these dimers connect to each
      other via C-H?O and N-H?O hydrogen bonds to form a three-dimensional network. 

PMID- 24454098
TI  - 4-Acetyl-3-[2-(eth-oxy-carbon-yl)phen-yl]sydnone.
AB  - Sydnones, which contain a mesoionic five-membered heterocyclic ring, are more
      stable if synthesized with an aromatic substutuent at the N3 position. In the
      title compound {sys-tematic name: 4-acetyl-3-[2-(eth-oxy-carbon-yl)phen-yl]-1,2,3
      oxa-diazol-3-ylium-5-olate}, C13H12N2O5, the aromatic substitutent is 2-(eth-oxy
      carbon-yl)phenyl. Intra- and inter-molecular hydrogen bonds are observed. The
      inter-planar angle between the sydnone and benzene rings is 71.94 (8) degrees .
      pi-ring?carbon-yl inter-actions of 3.2038 (16) A arise between the sydnone ring
      and a symmetry-related C=O group. 

PMID- 24454099
TI  - 1,5-Bis(4-iso-propyl-benzyl-idene)thio-carbonohydrazide.
AB  - The title compound, C21H26N4S, was synthesized by the condensation reaction of 4
      iso-propyl-benzaldehyde with thio-carbohydrazide in ethanol. The planes of the
      two benzene rings in the mol-ecule are inclined at 22.6 (1) degrees . In the
      crystal, pairs of inter-molecular N-H?S hydrogen bonds link the mol-ecules into
      inversion dimers. 

PMID- 24454100
TI  - 4-Meth-oxy-N-[(4-methyl-phen-yl)sulfon-yl]benzamide including an unknown solvate.
AB  - In the title compound, C15H15NO4S, the dihedral angle between the benzene rings
      is 78.62 (16) degrees . In the crystal, adjacent mol-ecules are linked along the
      c axis into C(4) chains through strong N-H?O hydrogen bonds. Mol-ecules are
      further connected through C-H?O hydrogen bonds into a hexa-meric unit generating
      an R (6) 6(66) motif. Another C-H?O inter-action connects the mol-ecules along
      the c axis, forming C(5) chains. A region of disordered electron density, most
      probably disordered methanol-water solvent mol-ecules, was treated with the
      SQUEEZE routine in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]. The formula
      mass and unit-cell characteristics do not take into account this disordered
      solvent. 

PMID- 24454101
TI  - Tri-phenyl-telluronium(IV) bromide acetone hemisolvate.
AB  - The asymmetric unit of the title compound, 2C18H15Te(+).2Br(-).C3H6O or
      Ph3TeBr.0.5Me2CO, contains two crystallographically independent tri-phenyl
      telluronium cations, two bromide anions, and one disordered [site-occupancy ratio
      = 0.581 (7):0.419 (7)] solvent mol-ecule. Inter-ionic Te?Br inter-actions connect
      the cations and anions into a tetra-meric step-like structure. The primary
      coordination spheres of both Te atoms are TeC3 trigonal pyramids: three short
      secondary tellurium-bromine inter-actions expand the coordination geometry of one
      of the Te atoms to an octa-hedron. While the other Te atom shows only two Te?Br
      secondary bonding inter-actions, it is also six-coordinated due to a Te?pi inter
      action [3.769 (2) A] with one of the phenyl rings of the adjacent cation. 

PMID- 24454102
TI  - Bis(l-serinium) oxalate dihydrate: polymorph II.
AB  - A corrected and improved structure of the polymorph II of 2C3H8NO3 (+).C2O4 (2
      ).2H2O, based on single-crystal data, is presented. The structure is refined with
      anisotropic displacement parameters for all non-H atoms and all H atoms are
      located. Due to the charged moieties, the structure is classified as a mol-ecular
      salt. Inter-molecular O-H?O(-), O-H?O and N(+)-H?O(-)hydrogen bonds link the
      components of the structure. The l-serinium cations and oxalate anions form a
      network of channels in [100] direction, filled with the water molecules of
      crystallization. The dihedral angle between the CO2 units of the oxalate dianion
      is 10.2 (3) degrees  

PMID- 24454103
TI  - Bis{4-[(1,3-benzodioxol-5-yl)meth-yl]piperazin-1-yl}methane.
AB  - In the title compound, C25H32N4O4, both piperazine rings adopt a chair
      conformation. One of dioxolane ring systems is essentially planar [dihedral angle
      = 0.9 (2) degrees ] while the other adopts a slightly disordered envelope
      conformation, the mean plane of the dioxolane ring being twisted by 3.6 (2)
      degrees  from that of the benzene ring. The dihedral angle between the benzene
      rings is 69.9 (5) degrees . No classical hydrogen bonds were observed. 

PMID- 24454104
TI  - Methyl 2-[4-(tri-fluoro-meth-yl)phenyl-sulfan-yl]benzoate.
AB  - In the title compound, C15H13F3O2S, the dihedral angle between the benzene rings
      is 79.5 (1) degrees . The ester group is twisted by 7.6 (1) degrees  from the
      mean plane of the adjacent benzene ring. Disorder was modeled over two sites for
      one F atom of the tri-fluoro-methyl group with an occupancy ratio of 0.54
      (6):0.46 (6). In the crystal, mol-ecules are linked via weak C-H?O hydrogen
      bonds, forming two-dimensional networks lying parallel to (101). The networks are
      linked via C-H?pi inter-actions, leading to the formation of a three-dimensional
      supra-molecular structure. 

PMID- 24454105
TI  - 1-[4-(4-Hy-droxy-phen-yl)piperazin-1-yl]ethanone.
AB  - In the title compound, C12H16N2O2, the piperazine ring has a chair conformation.
      The dihedral angle between the mean planes of the benzene ring and the acetyl
      group is 48.7 (1) degrees . In the crystal, mol-ecules are linked via O-H?O
      hydrogen bonds, forming chains propagating along [010]. 

PMID- 24454106
TI  - (R)-(-)-Quinuclidin-3-ol.
AB  - The structure of the title compound [alternatively called (R)-(-)-1-aza-bicyclo
      [2.2.2]octan-3-ol], C7H13NO, at 100 K has hexa-gonal (P61) symmetry. The
      structure shows a twist along the C-N pseudo-threefold axis. In the crystal, mol
      ecules are linked via O-H?N hydrogen bonds, forming infinite chains along the c
      axis direction. The crystal studied was twinned by merohedry (twin law: 010, 100,
      00-1; population: 0.925:0.075). 

PMID- 24454107
TI  - N-[5-(Di-phenyl-phosphorylmeth-yl)-4-(4-fluoro-phen-yl)-6-iso-propyl-pyrimi-din-2
      yl]-N-methyl-methane-sulfonamide.
AB  - In the title compound, C28H29FN3O3PS, the pyrimidine ring is oriented at a
      dihedral angle of 50.9 (2) degrees  with respect to the floro-benzene ring, while
      the two phenyl rings bonding to the same P atom are twisted with respect to each
      other, making a dihedral angle of 62.2 (2) degrees . In the crystal, mol-ecules
      are linked by weak C-H?O and C-H?F hydrogen bonds into a three-dimensional supra
      molecular architecture. 

PMID- 24454108
TI  - Bis(2,4,6-tri-amino-1,3,5-triazin-1-ium) 2-[bis-(carboxyl-atometh-yl)aza-nium
      yl]acetate trihydrate.
AB  - The title compound, 2C3H7N6 (+).C6H7NO6 (2-).3H2O, was obtained by mixing
      melamine and nitrilo-tri-acetic acid in aqueous solution. There is proton
      transfer from the nitrilo-triacteic acid to melamine to produce two melaminium
      cations and an inter-nal proton transfer to generate the [HN(CH2COO)](2-)
      zwitterion. The melaminium cations are arranged in hydrogen-bonded tapes formed
      by N-H?N inter-actions. These tapes extend parallel to the [010] direction and
      are stacked parallel to the a axis at a mean separation of 3.3559 (11) A. Between
      these tapes lie the anions and lattice water mol-ecules. Further O-H?O and N-H?O
      hydrogen bonds exist between the water mol-ecules, the anions, and the melaminium
      cations, generating a three-dimensional array. The crystal examined was found to
      be twinned by a twofold rotation about the direct lattice direction [100]. The
      two twin components were present in the ratio 0.5918:0.4082 (14). 

PMID- 24454110
TI  - N,N,N'-Tris[(1H-indol-3-yl)meth-yl]ethane-1,2-di-amine.
AB  - In the title mol-ecule, C29H29N5, the indole ring systems are essentially planar,
      with maximum deviations of 0.020 (2), 0.023 (2) and 0.016 (2) A. The dihedral
      angles formed between the mean planes of the three indole ring systems are 38.08
      (7), 89.64 (8) and 58.28 (8) degrees . In the crystal, mol-ecules are connected
      by N-H?N hydrogen bonds, forming inversion dimers. An intra-molecular N-H?N
      hydrogen bond is also observed. 

PMID- 24454109
TI  - (4-Hy-droxy-3,5-di-methyl-phen-yl)(phen-yl)methanone.
AB  - In the mol-ecule of the title compound, C15H14O2, the dihedral angle between the
      benzene and phenyl rings is 61.27 (8) degrees . In the crystal, O-H?O and weak C
      H?O hydrogen bonds link the mol-ecules into chains extending along the c-axis
      direction. 

PMID- 24454111
TI  - 2-(3-Nitro-phen-yl)-3-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one.
AB  - The title compound, C20H14N2O3S, has three aromatic rings, viz. (i) a phenyl
      ring, (ii) a 3-nitro-phenyl and (iii) a 1,3-benzo-thia-zine fused-ring system.
      The dihedral angle between (i) and (ii) is 85.31 (15) degrees , between (ii) and
      (iii) is 81.33 (15) degrees  and between (i) and (iii) is 75.73 (15) degrees .
      The six-membered 1,3-thia-zine ring has an envelope conformation with the C atom
      in the 2-position forming the flap. In the crystal, mol-ecules are linked by weak
      C-H?O inter-actions, forming a three-dimensional network. 

PMID- 24454112
TI  - 3-(1,3-Di-phenyl-propan-2-yl)-4-methyl-6-phenyl-isoxazolo[3,4-d]pyridazin-7(6H)
      one.
AB  - In the title compound, C27H23N3O2, the geminal benzyl groups branching out from
      the methine adjacent to the isoxazole group are both syn-oriented to the methyl
      group of the pyridazinone moiety, as reflected by C-C distances of 3.812 (2) and
      4.369 (2) A between the methyl carbon and the nearest ring carbon of each benzyl
      group. This kind of conformation is retained in CDCl3 solution, as evidenced by
      distinct phenyl-shielding effects on the (1)H NMR signals of the methyl H atoms.
      The isoxazolo[3,4-d]pyridazin ring system is virtually planar (r.m.s. deviation
      from planarity = 0.031 A), but the N-bonded phenyl group is inclined to the
      former by an ring-ring angle of 55.05 (3) degrees . In the crystal, the T-shaped
      mol-ecules are arranged in an inter-locked fashion, forming rod-like assemblies
      along [10-1]. The mol-ecules are held together by unremarkable weak C-H?N, C-H?O
      and C-H?pi inter-actions (C-O,N,C > 3.4 A), while significant pi-pi-stacking
      inter-actions are absent. 

PMID- 24454113
TI  - 2,4,6-Tri-nitro-phenyl furan-2-carboxyl-ate.
AB  - In the title carboxyl-ate derivative, C11H5N3O9, the picryl ring forms an angle
      of 75.79 (7) degrees  with the ester fragment, indicating a near perpendicular
      disposition. The nitro substituents are variously oriented with respect to the
      picryl ring [dihedral angles = 3.22 (10), 16.03 (12) and 36.63 (10) degrees ]. In
      the crystal, mol-ecules form helical chains sustained by C-H?O inter-actions
      along [010]. The furanyl residue is disordered, having two coplanar slightly
      displaced orientations [major component = 0.730 (9)]. 

PMID- 24454114
TI  - (6-Meth-oxy-2-oxo-2H-chromen-4-yl)methyl piperidine-1-carbodi-thio-ate.
AB  - In the title compound, C17H19NO3S2, the maximum deviation of atoms in the 2H
      chromene ring system is 0.0097 (14) A and the piperidine ring adopts a chair
      conformation. The dihedral angle between the 2H-chromene ring and the piperidine
      ring (all atoms) is 87.59 (8) degrees . In the crystal, inversion dimers linked
      by pairs of C-H?O inter-actions generate R 2 (2)(22) loops. Further C-H?O
      hydrogen bonds link the dimers into [110] chains and weak aromatic pi-pi stacking
      [shortest centroid-centroid distance = 3.824 (8) A] is also observed. 

PMID- 24454115
TI  - (7-Chloro-2-oxo-2H-chromen-4-yl)methyl pyrrolidine-1-carbodi-thio-ate.
AB  - In the title compound, C15H14ClNO2S2, the 2H-chromene ring system is essentially
      planar, with a maximum deviation of 0.0133 (10) A. Three C atoms and their
      attached H atoms of the pyrrolidine ring are disordered [occupany ratio 0.874
      (7):0.126 (7)] with both disorder components adopting a twisted conformation. The
      dihedral angle between the 2H-chromene ring system and the major occupancy
      component of the pyrrolidine ring is 89.45 (7) degrees . In the crystal,
      inversion dimers linked by pairs of C-H?S and C-H?O inter-actions generate R (2)
      2(24) and R (2) 2(10) loops, respectively. Further C-H?O hydrogen bonds link the
      dimers into [100] chains. C-H?pi inter-actions also occur and there is very weak
      pi-pi stacking [inter-planar spacing = 3.650 (5) A; centroid-centroid distance =
      4.095 (7) A] between inversion-related chloro-benzene rings. 

PMID- 24454116
TI  - Propyl 2-(1H-indol-3-yl)acetate.
AB  - In the title compound, C13H15NO2, the acetate group [C-C(=O)-O] makes a dihedral
      angle of 62.35 (13) degrees  with the mean plane of the indole ring system
      [maximum deviation = 0.011 (3) A]. In the crystal, mol-ecules are linked by N-H?O
      hydrogen bonds, forming helical chains propagating along [010]. 

PMID- 24454117
TI  - 4-Methyl-N-(4-nitro-benzyl-idene)piperazin-1-amine.
AB  - In the title compound, C12H16N4O2, the piperazine ring is in a slightly distorted
      chair conformation. In the mol-ecule, the mean plane of the nitro group is
      twisted by 8.0 (3) degrees  from that of the benzene ring. Also, the mean plane
      of the 2-nitro-benzyl ring is twisted slightly from that of the piperazine ring,
      with an N-N=C-C torsion angle of -176.24 (11) degrees . In the crystal, pairs of
      weak C-H?O inter-actions link the mol-ecules into dimers approximately along
      [010]. 

PMID- 24454118
TI  - 2-(3,4-Di-fluoro-phen-yl)-1H-benzimidazole.
AB  - In the title mol-ecule, C13H8F2N2, the dihedral angle between the benzimidazole
      ring system and the di-fluoro-substituted benzene ring is 30.0 (1) degrees . In
      the crystal, mol-ecules are linked by N-H?N hydrogen bonds, forming chains along
      [010]. In addition, weak C-H?F hydrogen bonds connect chains into a two
      dimensional network parallel to (001). A weak C-H?pi inter-action is observed
      between an H atom of the benzimidazole ring sytem and the pi system of the di
      fluoro-substituted benzene ring. 

PMID- 24454119
TI  - 6-Hy-droxy-5-[(2-hy-droxy-4,4-dimethyl-6-oxo-cyclo-hex-1-en-yl)(4-nitro-phen
      yl)meth-yl]-1,3-di-methyl-pyrimidine-2,4(1H,3H)-dione.
AB  - In the title compound, C21H23N3O7, the pyrimidine-dione ring adopts a screw-boat
      conformation, whereas the cyclo-hexenone ring adopts an envelope conformation,
      with the C atom bearing the methyl groups as the flap atom. The dihedral angle
      between the mean planes of the pyrimidine-dione and cyclo-hexenone rings is 58.78
      (2) degrees . The pyrimidine-dione and cyclo-hexenone rings form dihedral angles
      of 59.94 (3) and 54.73 (2) degrees , respectively, with the 4-nitro-phenyl ring.
      Relatively strong intra-molecular O-H?O hydrogen bonds are observed. In the
      crystal, mol-ecules are linked by C-H?O hydrogen bonds, forming a chain along the
      c-axis direction. 

PMID- 24454120
TI  - Absolute configuration of (1S,3R,8R)-10-bromo-methyl-2,2-di-chloro-3,7,7-tri
      methyl-tri-cyclo-[6.4.0.0(1,3)]dodec-9-ene.
AB  - The absolute configuration of the title compound, C16H23BrCl2, has been deduced
      from the chemical pathway and fully confirmed by refinement of the Flack and
      Hooft parameters. The six-membered ring adopts a half-chair conformation, whereas
      the seven-membered ring is a twisted chair. The mol-ecular packing within the
      crystal is stabilized only by van der Waals inter-actions. 

PMID- 24454121
TI  - Second monoclinic form of (E)-3-(4-fluoro-phen-yl)-1-phenyl-prop-2-en-1-one.
AB  - The unit-cell dimensions and space group of the second monoclinic polymorph of
      the title compound, C15H11FO, differ from those of the previously reported form
      [Jing (2009 ?). Acta Cryst. E65, o2515]. The title compound shows an E
      conformation of the C=C bond with the 4-fluoro-phenyl group opposite to the
      benzoyl group. The torsion angle of between the planes of the 4-fluoro-phenyl and
      benzoyl groups is 10.53 (6) degrees . In the crystal, weak C-H?O and C-H?F inter
      actions form a cross-linked packing motif, building sheets parallel to (-102). 

PMID- 24454122
TI  - 1-(4-Chlorophenyl)-3-(3-chloro-pro-pionyl)thio-urea.
AB  - In the title compound, C10H10Cl2N2OS, the mol-ecule adopts a trans-cis
      conformation with respect to the position of the carbonyl group and the chloro
      phenyl groups relative to the thiono group across the C-N bonds. The mol-ecule is
      stabilized by an N-H?O hydrogen bond. In the crystal, mol-ecules are linked by N
      H?S and C-H?O hydrogen bonds, forming zigzag chains along the b-axis direction. C
      H?pi inter-actions are also present. 

PMID- 24454123
TI  - 2-[(1H-Pyrrol-2-yl)meth-yl]-1H-pyrrole.
AB  - In the title compound, C9H10N2, the two pyrrole ring planes are twisted by a
      dihedral angle of 69.07 (16) degrees  and the C-C-C methane angle is 115.1 (2)
      degrees . In the crystal, mol-ecules are connected into layers in the bc plane by
      N-H?pi inter-actions. 

PMID- 24454124
TI  - Methyl 1-allyl-4-hy-droxy-2,2-dioxo-1H-2lambda(6),1-benzo-thia-zine-3-carboxyl
      ate.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C13H13NO5S, in both of which the ester substituent is nearly coplanar
      [C-C-C-O torsion angles = 2.7 (7) and -0.8 (7) degrees ] with the planar fragment
      of the bicycle due to the formation of a strong O-H?O intra-molecular hydrogen
      bond. The vinyl group at the ring N atom is approximately orthogonal to the
      heterocyclic mean plane [C-N-C-C torsion angles = 103.1 (6) and 98.2 (5) degrees
      ]. The refinement was performed on a two-component, non-merohedrally twinned
      crystal [population ratio = 0.483 (3):0.517 (3). 

PMID- 24454125
TI  - 1-Acetyl-5-(4-fluoro-phen-yl)-2-sulfanyl-ideneimidazolidin-4-one.
AB  - In the title compound, C11H9FN2O2S, the 2-sulfanylideneimidazolidin-4-one moiety
      is essentially planar, with a maximum deviation of 0.0183 (14) A. The mean plane
      of this moiety is approximately coplanar with the attached acetyl group and
      perpendicular to the benzene ring, making dihedral angles of 9.70 (14) and 86.70
      (6) degrees , respectively. In the crystal, mol-ecules are linked by N-H?O
      hydrogen bonds between the amide NH and acetyl C=O groups, forming a C(6) chain
      along the a-axis direction. 

PMID- 24454126
TI  - N-[(1,3-Benzodioxol-5-yl)meth-yl]benzene-sulfonamide: an analogue of capsaicin.
AB  - The title compound, C14H13NO4S, an analogue of capsaicin, differs from the latter
      by having a 1,3-benzodioxole ring rather than a 2-meth-oxy-phenol moiety, and
      having a benzene-sulfonamide group instead of an aliphatic amide chain. The five
      membered ring is in an envelope conformation with the methyl-ene C atom lying
      0.221 (6) A out of the plane formed by the other four atoms. The dihedral angle
      between the phenyl ring and the mean plane of the 1,3-benzodioxole fused-ring
      system is 84.65 (4) degrees . In the crystal, mol-ecules aggregate into supra
      molecular layers in the ac plane through C-H?O, N-H?O and C-H?pi inter-actions. 

PMID- 24454127
TI  - 6-(4-Chloro-phen-yl)-3-methyl-imidazo[2,1-b]thia-zole.
AB  - In the title compound, C12H9ClN2S, the imidazo[2,1-b]thia-zole fragment is planar
      (r.m.s. deviation = 0.003 A), and the benzene ring is twisted slightly [by 5.65
      (6) degrees ] relative to this moiety. In the crystal, mol-ecules are linked by
      pi-pi stacking inter-actions into columns along [010]. The mol-ecules within the
      columns are arranged alternatively by their planar rotation of 180 degrees .
      Thus, in the columns, there are the two types of pi-pi stacking inter-actions,
      namely, (i) between two imidazo[2,1-b]thia-zole fragments [inter-planar distance
      = 3.351 (2) A] and (ii) between an imidazo[2,1-b]thia-zole fragment and the
      phenyl ring [inter-planar distance = 3.410 (5) A]. There are no short contacts
      between the columns. 

PMID- 24454128
TI  - N-(1H-Indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.
AB  - In the title compound, C14H13N3O3S, the fused ring system is almost planar, the
      largest deviation from the mean plane being 0.023 (2) A, and makes a dihedral
      angle of 47.92 (10) degrees  with the benzene ring of the benzene-sulfonamide
      moiety. In the crystal, mol-ecules are connected through N-H?O hydrogen bonds and
      weak C-H?O contacts, forming a two-dimensional network which is parallel to
      (010). 

PMID- 24454129
TI  - (1R,4R,6S,7S)-5,5-Di-chloro-1,4,8,8-tetra-methyl-tri-cyclo
      [5.4.1(1,7).0(4,6)]dodecan-12-one.
AB  - The title compound, C16H24Cl2O, was synthesized in three steps from beta
      himachalene (3,5,5,9-tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo
      heptene), which was isolated from essential oil of the Atlas cedar (cedrus
      atlantica). The asymmetric unit contains two independent mol-ecules with similar
      conformations. Each mol-ecule is built up from two fused seven-membered rings and
      an additional three-membered ring arising from the reaction of himachalene with
      di-chloro-carbene. The dihedral angles between the mean planes of the two seven
      membered rings are 75.03 (9) and 75.02 (9) degrees  in the two independent mol
      ecules. 

PMID- 24454130
TI  - 2-[4-(Tri-fluoro-meth-yl)phenyl-sulfan-yl]benzoic acid.
AB  - In the title compound, C14H9F3O2S, the dihedral angle between the mean planes of
      the benzene rings is 88.7 (2) degrees . The carb-oxy-lic acid group is twisted by
      13.6 (7) degrees  from the mean plane of its attached aromatic ring. One of the F
      atoms of the tri-fluoro-methyl group is disordered over two sites in a 0.61
      (7):0.39 (7) ratio. In the crystal, inversion dimers linked by pairs of O-H?O
      hydrogen bonds generate R 2 (2)(8) loops. Weak C-H?F inter-actions are also
      observed. 

PMID- 24454131
TI  - 1-(3,5-Di-fluoro-phen-yl)-4,4,4-tri-fluoro-butane-1,3-dione.
AB  - In the title compound, C10H5F5O2, the C=O bonds are syn to one another. In the
      crystal, mol-ecules are linked into C(9) chains parallel to [101] through weak C
      H?O inter-actions, with the O atom adjacent to the -CF3 group acting as the
      acceptor. 

PMID- 24454132
TI  - N-(1H-Indol-3-yl-methyl-idene)-4-methyl-piperazin-1-amine.
AB  - In the title compound, C14H18N4, the piperazine ring is in a slightly distorted
      chair conformation. The indole ring system is twisted from the piperazine ring,
      making a dihedral angle of 7.27 (11) degrees . In the crystal, N-H?N hydrogen
      bonds link mol-ecules into chains along [10-1]. 

PMID- 24454133
TI  - 4-Hy-droxy-5-(2-meth-oxy-phen-oxy)-2,2'-bipyrimidin-6(5H)-one dihydrate.
AB  - The title compound, C15H12N4O4.2H2O, crystallizes with two independent water mol
      ecules in the asymmetric unit. The dihedral angles between the mean planes of the
      benzene and pyrimidine rings and that of the pyrimidin-4-one ring are 85.1 (9)
      and 82.1 (1) degrees , respectively. The mean plane of the pyrimidine ring is
      twisted by 12.8 (8) degrees  from that of the pyrimidin-4-one ring. The dihedral
      angles between the benzene ring and the mean planes of the pyrimidine and
      pyrimidin-4-one rings are 85.1 (9) and 82.1 (1) degrees , respectively.In the
      crystal, N-H?O, O-H?N and O-H?O hydrogen bonds involving both water mol-ecules
      are present; these link the mol-ecules into a two-dimensional network parallel to
      (010). In addition, weak C-H?pi and pi-pi [centroid-centroid distance = 3.6183
      (8) A] inter-actions occur. 

PMID- 24454135
TI  - (2R,2'S)-2,2'-Bi-piperidine-1,1'-diium dibromide.
AB  - The title compound, C10H22N2 (2+).2Br(-), was synthesized via reduction of 2,2'
      dipyridyl with Ni-Al alloy/KOH, followed by separation of diastereoisomers (meso
      and rac) by recrystallization from ethanol. Although the two bridging C atoms are
      optically active, these two chiral centers adopt an (S,R) configuration; thus,
      the title compound contains an achiral meso form of 2,2'-bi-piperidine. Both of
      the piperidinium rings adopt chair conformations, and the two N atoms are trans
      to each other; an inversion center is located in the mid-point of the central C-C
      bond. The conformation of the organic moiety resembles that of 1,1'-bi(cyclo-hexa
      ne). The organic di-ammonium cations are linked to each other through hydrogen
      bonding with bromide counter-ions, each of which forms two hydrogen bonds (N
      H?Br) with two adjacent organic cations, thus linking the latter together in
      sheets parallel to (100). 

PMID- 24454134
TI  - (E)-13-(4-Amino-phen-yl)parthenolide.
AB  - The title compound, C21H25NO3 [systematic name: (3aS,9aR,10aR,10bS,E)-3-[(E)-4-(4
      amino-benzyl-idene)-6,9a-dimethyl-3a,4,5,8,9,9a,10a,10b-octa-hydro
      oxireno[2',3':9,10]cyclo-deca-[1,2-b]furan-2(3H)-one] was obtained from the
      reaction of parthenolide [synonym: 4,5-ep-oxy-germacra-1(10),11(13)-dieno-12,6
      lactone] with 4-iodo-aniline under Heck reaction conditions. It was identified as
      the E-isomer (conformation about the exocyclic methyl-idene C=C bond; the
      conformation about the C=C bond in the ten-membered ring is also E). The mol
      ecule is built up from fused ten-, five- (lactone) and three-membered (epoxide)
      rings with a 4-amino-phenyl group as a substituent. The ten-membered ring
      displays an approximate chair-chair conformation, while the lactone ring has an
      envelope conformation with the C atom bonded to the ring O atom as the flap. The
      dihedral angle between the benzene ring of the 4-amino-phenyl moiety and the
      lactone ring mean plane is 23.50 (8) degrees . In the crystal, mol-ecules are
      linked via N-H?O hydrogen bonds, between the amine group and the lactone and
      epoxide ring O atoms, forming chains propagating along the b-axis direction.
      Adjacent chains are linked via C-H?O inter-actions, forming an undulating two
      dimensional network lying parallel to the plane (001). The absolute structure of
      the mol-ecule in the crystal was confirmed by resonance scattering [Flack
      parameter = 0.03 (3)]. 

PMID- 24454136
TI  - N-(2-Chloro-acet-yl)glycine.
AB  - The title compound, C4H6ClNO3, crystallizes with two independent mol-ecules (A
      and B) in the asymmetric unit. In each mol-ecule, there are N-H?O and N-H?Cl
      hydrogen bonds. Both mol-ecules are relatively planar, with the mean plane of the
      acetamide [N-C(=O)C] group being inclined to the mean plane of the acetate group
      [C-C(=O)O] by 9.23 (13) degrees  in mol-ecule A and 6.23 (12) degrees  in mol
      ecule B. In the crystal, adjacent mol-ecules are linked by O-H?O hydrogen bonds
      and weak C-H?O contacts forming -A-A-A- and -B-B-B- parallel chains propagating
      along the a-axis direction. 

PMID- 24454137
TI  - N,N,N-Tri-butyl-butan-1-aminium (T-4)-(cyano-kappaC)tri-hydro-borate.
AB  - In the crystal structure of the title salt, C16H36N(+).CH3BN(-), the tetra-n
      butyl-ammonium cations and [BH3(CN)](-) anions are connected via weak C-H?N inter
      actions, forming chains along the b-axis direction. The anion is almost linear
      with an N-C-B angle of 178.7 (2) degrees . The C-N-C angle values at the core of
      the tetra-n-butyl-ammonium cation range from 105.74 (11) to 111.35 (11) degrees 
      with an average of 109.49 (11) degrees , close to the ideal tetra-hedral value. 

PMID- 24454138
TI  - 6,6'-Dieth-oxy-2,2'-[4-methyl-1,2-phenyl-enebis(nitrilo-methanylyl
      idene)]diphenol aceto-nitrile monosolvate.
AB  - The title solvated Schiff base compound, C25H26N2O4.CH3CN, possesses an O2N2
      donor set affording a potentially tetra-dentate metal complex ligand. The central
      ring makes dihedral angles of 6.7 (3) and 48.4 (2) degrees  with the pendant
      rings. Intra-molecular N-H?O hydrogen-bonding inter-actions are observed. 

PMID- 24454139
TI  - 2-Isopropyl-4-meth-oxy-5-methyl-phenyl acetate.
AB  - In the title compound, C13H18O3, the benzene ring is almost perpendicular to the
      acet-oxy plane, making a dihedral angle of 89.33 (11) degrees . In the crystal,
      mol-ecules are linked by weak C-H?O hydrogen bonds, forming a zigzag chain along
      the c-axis direction. 

PMID- 24454140
TI  - N-[(2-Chloro-phen-yl)sulfon-yl]-2-meth-oxy-benzamide.
AB  - The title compound, C14H12ClNO4S, crystallizes with two mol-ecules in the
      asymmetric unit. The dihedral angles between the benzene rings are 89.68 (1) (mol
      ecule 1) and 82.9 (1) degrees  (mol-ecule 2). In each mol-ecule, intra-molecular
      N-H?O hydrogen bonds between the amide H atom and the meth-oxy O atom generate
      S(6) loops. In the crystal, mol-ecule 2 is linked into inversion dimers through
      pairs of C-H?O inter-actions, forming an R 2 (2)(8) ring motif. Mol-ecules 1 and
      2 are further linked along the b-axis direction through C-H?pi inter-actions. The
      crystal structure is further stabilized by several pi-pi stacking inter-actions
      [centroid-centroid separations = 3.7793 (1), 3.6697 (1) and 3.6958 (1) A], thus
      generating a three-dimensional architecture. 

PMID- 24454141
TI  - 4-Meth-oxy-N-(pyridin-4-ylmeth-yl)-3-(tri-fluoro-meth-yl)benzamide monohydrate.
AB  - In the title compound, C15H13F3N2O2.H2O, the dihedral angle between the benzene
      and pyridine rings is 74.97 (1) degrees . The -CF3 group attached to the benzene
      ring is syn to the C=O bond in the adjacent side chain. In the crystal, mol
      ecules are linked to one another through the water mol-ecules by strong N-H?O, O
      H?O and O-H?N hydrogen bonds, forming a ladder-type network. The benzamide mol
      ecules are also linked to one another through C-H?F inter-actions, forming C(6)
      chains parallel to the b-axis direction. Aromatic pi-pi stacking inter-actions
      [centroid-centroid separations = 3.7150 (1) and 3.7857 (1) A] between adjacent
      pairs of pyridine and benzene rings are also observed, resulting in a three
      dimensional architecture are also observed. 

PMID- 24454142
TI  - 2-(2-Chloro-8-methyl-quinolin-3-yl)-4-phenyl-1,2-di-hydro-quinazoline.
AB  - In the title compound, C24H18ClN3, the di-hydro-quinazoline and methyl
      substituted quinoline benzene rings make a dihedral angle of 78.18 (4) degrees 
      and form dihedral angles of 45.91 (5) and 79.80 (4) degrees , respectively, with
      the phenyl ring. The dihedral angle between the phenyl ring of di-hydro
      quinazoline and the methyl-substituted benzene ring of quinoline is 78.18 (4)
      degrees . The crystal packing can be described as crossed layers parallel to the
      (011) and (0-11) planes. The structure features N-H?N hydrogen bonds and pi-pi
      inter-actions [centroid-centroid distance between phenyl rings = 3.7301 (9) A]. 

PMID- 24454143
TI  - 1,4-Bis(hex-yloxy)benzene.
AB  - The asymmetric unit of the title compound, C18H30O2, contains one half-mol-ecule
      situated on an inversion center. The alkyl chain adopts a fully extended all
      trans conformation. The C atoms of the alkyl chain are almost coplanar, with a
      maximum deviation of 0.042 (6) A from the mean plane,which is inclined to the
      central benzene ring by 6.80 (9) degrees . The crystal packing exhibits no short
      inter-molecular contacts. 

PMID- 24454144
TI  - 4-Ethynyl-N,N-di-phenyl-aniline.
AB  - The asymmetric unit of the title compound, C20H15N, comprises two
      crystallographically independent mol-ecules (A and B). In each mol-ecule, the N
      atom adopts an approximately trigonal planar geometry, lying 0.009 (1) or 0.003
      (1) A from the plane defined by the C atoms of the aromatic substituents to which
      it is attached. In the crystal, mol-ecules are linked via C-H?pi inter-actions,
      forming a three-dimensional structure. 

PMID- 24454145
TI  - Pyrrolidinium-2-carboxyl-ate-4-nitro-phenol (1/2).
AB  - In the title compound, C5H9NO2.2C6H5NO3, the pyrrolidine ring of the
      pyrrolidinium-2-carboxyl-ate zwitterion adopts a twisted conformation on the -CH2
      CH2- bond adjacent to the N atom. The mean plane of this pyrrolidine ring forms
      dihedral angles of 25.3 (3) and 32.1 (3) degrees  with the two nitro-phenol
      rings. An intra-molecular N-H?O hydrogen bond occurs in the pyrrolidinium-2
      carboxyl-ate mol-ecule. In the crystal, mol-ecules are linked via O-H?O and N-H?O
      hydrogen bonds, enclosing R (3) 2(8) ring motifs, forming chains running parallel
      to the a axis. These chains are further cross-linked by O-H?O and C-H?O hydrogen
      bonds, forming undulating two-dimensional networks lying parallel to (001). 

PMID- 24454146
TI  - 1-[5-Methyl-1-(4-nitro-phen-yl)-1H-1,2,3-triazol-4-yl]ethanone.
AB  - The asymmetric unit of the title compound, C11H10N4O3, contains two independent
      mol-ecules in which the benzene rings make dihedral angles of 38.3 (2) and 87.1
      (2) degrees  with respect to the triazole rings. In the crystal, the mol-ecules
      are linked by C-H?O hydrogen bonds, forming chains along [021]. Further, weak C
      O?pi [3.865 (5) A, 83.8 (3) degrees ] and N-O?pi [3.275 (5) and 3.240 (6) A,
      141.8 (4) and 102.8 (3) degrees ] inter-actions are observed. 

PMID- 24454147
TI  - Uronium 3-carb-oxy-4-hy-droxy-benzene-sulfonate.
AB  - In the title compound, CH5N2O(+).C7H5O6S(-), the dihedral angle between the
      benzene ring and the mean plane of the uronium cation is 76.02 (8) degrees . The
      carboxyl group in the anion is twisted by 1.47 (9) degrees  from the benzene
      ring. In the crystal, the cation is linked to the anion by weak O-H?O and N-H?O
      hydrogen bonds and pi-pi inter-actions [centroid-centroid distance = 3.8859 (8)
      A], forming a three-dimensional network. 

PMID- 24454148
TI  - Revision of the Li13Si4 structure.
AB  - Besides Li17Si4, Li16.42Si4, and Li15Si4, another lithium-rich representative in
      the Li-Si system is the phase Li13Si4 (trideca-lithium tetra-silicide), the
      structure of which has been determined previously [Frank et al. (1975 ?). Z.
      Naturforsch. Teil B, 30, 10-13]. A careful analysis of X-ray diffraction patterns
      of Li13Si4 revealed discrepancies between experimentally observed and calculated
      Bragg positions. Therefore, we redetermined the structure of Li13Si4 on the basis
      of single-crystal X-ray diffraction data. Compared to the previous structure
      report, decisive differences are (i) the introduction of a split position for one
      Li site [occupancy ratio 0.838 (7):0.162 (7)], (ii) the anisotropic refinement of
      atomic displacement parameters for all atoms, and (iii) a high accuracy of atom
      positions and unit-cell parameters. The asymmetric unit of Li13Si4 contains two
      Si and seven Li atoms. Except for one Li atom situated on a site with symmetry
      2/m, all other atoms are on mirror planes. The structure consists of isolated Si
      atoms as well as Si-Si dumbbells surrounded by Li atoms. Each Si atom is either
      12- or 13-coordinated. The isolated Si atoms are situated in the ab plane at z =
      0 and are strictly separated from the Si-Si dumbbells at z = 0.5. 

PMID- 24454149
TI  - The P43 enanti-omorph of Sr2As2O7.
AB  - The crystal structure of strontium diarsenate has been reinvestigated from single
      crystal X-ray diffraction data. In contrast to the previous determinations of
      this structure [Weil et al. (2009 ?). Solid State Sci. 11, 2111-2117; Edhokkar et
      al. (2012 ?). Mater. Sci. Eng., 28, 012017] and to all isotypic A 2 B 2O7
      compounds that crystallize in the space group P41, the current redetermination
      revealed the P43 enanti-omorph of Sr2As2O7 with a purity of 96.3 (8)%. The
      crystal structure is made up from two eclipsed As2O7 diarsenate groups (symmetry
      1) with characteristically longer As-O bridging bonds [1.756 (4)-1.781 (4) A]
      than the terminal As-O bonds [1.636 (4)-1.679 (4) A] and four Sr(2+) sites with
      coordination numbers ranging from seven to nine. The building units are arranged
      in sheets parallel to (001). 

PMID- 24454150
TI  - Na3Co2(As0.52P0.48)O4(As0.95P0.05)2O7.
AB  - The title compound, trisodium dicobalt(II) (arsenate/phosphate)
      (diarsenate/diphosphate), was prepared by a solid-state reaction. It is
      isostructural with Na3Co2AsO4As2O7. The framework shows the presence of CoX22O12
      (X2 is statistically disordered with As0.95P0.05) units formed by sharing corners
      between Co1O6 octa-hedra and X22O7 groups. These units form layers perpendicular
      to [010]. Co2O6 octa-hedra and X1O4 (X1 = As0.54P0.46) tetra-hedra form Co2X1O8
      chains parallel to [001]. Cohesion between layers and chains is ensured by the
      X22O7 groups, giving rise to a three-dimensional framework with broad tunnels,
      running along the a- and c-axis directions, in which the Na(+) ions reside. The
      two Co(2+) cations, the X1 site and three of the seven O atoms lie on special
      positions, with site symmetries 2 and m for the Co, m for the X1, and 2 and m (*
      2) for the O sites. One of two Na atoms is disordered over three special
      positions [occupancy ratios 0.877 (10):0.110 (13):0.066 (9)] and the other is in
      a general position with full occupancy. A comparison between structures such as
      K2CdP2O7, alpha-NaTiP2O7 and K2MoO2P2O7 is made. The proposed structural model is
      supported by charge-distribution (CHARDI) analysis and bond-valence-sum (BVS)
      calculations. The distortion of the coordination polyhedra is analyzed by means
      of the effective coordination number. 

PMID- 24454151
TI  - Poly[MU-aqua-MU5-[2-(2,3,6-tri-chloro-phenyl)acetato]-caesium].
AB  - In the structure of the title complex, [Cs(C8H4Cl3O2)(H2O)] n , the caesium salt
      of the commercial herbicide fenac [(2,3,6-tri-chloro-phen-yl)acetic acid], the
      irregular eight-coordination about Cs(+) comprises a bidentate O:Cl-chelate inter
      action involving a carboxyl-ate-O atom and an ortho-related ring-substituted Cl
      atom, which is also bridging, a triple-bridging carboxyl-ate-O atom and a
      bridging water mol-ecule. A two-dimensional polymer is generated, lying parallel
      to (100), within which there are water-carboxyl-ate O-H?O hy-dro-gen-bonding
      inter-actions. 

PMID- 24454152
TI  - Di-MU 2-acetato-1:2kappa (2) O:O';2:3kappa (2) O:O'-bis-{MU 2-4,4'-di-chloro-2,2'
      [2,2-di-methyl-propane-1,3-diylbis(nitrilo-methanylyl-idene)]diphenolato}
      1:2kappa (6) O,N,N',O':O,O';2:3kappa (6) O,O':O,N,N',O'-tri-cadmium.
AB  - In the title linear homo-trinuclear complex, [Cd3(C19H18Cl2N2O2)2(C2H3O2)2], the
      central Cd(II) atom is located on a centre of inversion and has a distorted octa
      hedral coordination geometry formed by four O atoms from two bidentate/tetra
      dentate Schiff base ligands and two O atoms from two bridging acetate ligands.
      The coordination geometry of the terminal Cd(II) atom is square-pyramidal with
      the tetra-dentate part of the ligand in the basal plane and one O atom from an
      acetate ligand occupying the apical site. The six-membered CdN2C3 ring adopts a
      chair conformation. The acetate-bridged Cd?Cd distance is 3.3071 (2) A. The
      crystal structure is stabilized by C-H?O hydrogen bonds, which form C(7) chain
      motifs and give rise to a two-dimensional supra-molecular network structure lying
      parallel to the ab plane. 

PMID- 24454153
TI  - {2,2'-[Ethane-1,2-diylbis(nitrilo-methan-yl-yl-idene)]diphenolato}(iso-propano
      lato)aluminium di-chloro-methane hemisolvate.
AB  - In the title compound, [Al(C16H14N2O2)(C3H7O)].0.5CH2Cl2, the salen complex is
      monomeric and the dichlormethane solvent mol-ecule lies on a crystallographic
      twofold axis. The central Al atom is fivefold coordinated and possesses a square
      based pyramidal environment. The Al-OAlk( (i) prop-yl) bond [1.7404 (14) A] is
      much shorter than the Al-OAr(salen) bond lengths [1.7974 (15) and 1.8094 (14) A].
      The iso-propyl-oxo group forms an intra-molecular C-H?N hydrogen bond. In the
      crystal, the complex mol-ecules are linked by weak C-H?O inter-actions. 

PMID- 24454154
TI  - (2-{[4-(Chlorido-mercur-yl)phen-yl]imino-meth-yl}pyridine-kappa(2) N,N')di-iodido
      mercury(II) dimethyl sulfoxide monosolvate.
AB  - The title dimethyl sulfoxide solvate, [Hg2(C12H9ClN2)I2].C2H6OS, features tetra
      hedrally and linearly coordinated Hg(II) atoms. The distorted tetrahedral
      coordination sphere is defined by chelating N atoms that define an acute angle
      [69.6 (3) degrees ] and two I atoms that form a wide angle [142.80 (4) degrees ].
      The linearly coordinated Hg(II) atom [177.0 (4) degrees ] exists with a donor set
      defined by C and Cl atoms. Secondary inter-actions are apparent in the crystal
      packing with the tetra-hedrally and linearly coordinated Hg(II) atoms expanding
      their coordination environments by forming weak Hg?I [3.772 (7) A] and Hg?O
      [2.921 (12) A] inter-actions, respectively. Mercury-containing mol-ecules stack
      along the a axis, are connected by pi-pi inter-actions [inter-centroid distance
      between pyridine and benzene rings = 3.772 (7) A] and define channels in which
      the dimethyl sulfoxide mol-ecules reside. The latter are connected by the
      aforementioned Hg?O inter-actions as well as C-H?I and C-H?O inter-actions,
      resulting in a three-dimensional architecture. 

PMID- 24454155
TI  - Di-MU-oxido-bis-({2,2'-[ethane-1,2-diylbis(nitrilo-methanylyl-idene)]diphen
      olato}titanium(IV)) chloro-form disolvate.
AB  - In the title structure, [Ti2(C16H16N2O2)2O2].2CHCl3, the Ti atom is coordinated
      in a distorted octa-hedral geometry by the O,N,N',O' donor set of the salalen
      ligand and by two MU2-oxide O atoms, which bridge two Ti(salalen) fragments into
      a centrosymmetric dimeric unit. In the central Ti2(MU2-O)2 fragment, the metal
      oxygen distances are significantly different [1.7962 (19) and 1.9292 (19) A]. In
      the crystal, the chloro-form mol-ecule is anchored via an N-H?Cl and a bifurcated
      C-H?(O,O) hydrogen bond. Slipped pi-pi stacking [shortest C?C distance = 3.585
      (4) A] and C-H?pi inter-actions contribute to the coherence of the structure. 

PMID- 24454156
TI  - catena-Poly[N,N,N',N'-tetra-methyl-ethylendi-ammonium [[tetra-bromido
      antimonate(III)]-MU-bromido] hemihydrate].
AB  - The asymmetric unit of the title compound {(C6H18N2)2[Sb2Br10].H2O} n , consists
      of two tetra-methyl-ethylendi-ammonium cations that are located on centres of
      inversion, as well as one tetra-methyl-ethylendi-ammonium cation, one water mol
      ecule, one distorted octahedral [SbBr6](3-)anion and one bisphenoidal [SbBr4](-)
      anion in general positions. The [SbBr6](3-) and [SbBr4](-) anions are linked
      together by two long Sb-Br bonds of 3.2709 (8) and 3.5447 (7) A into {[Sb2Br10](4
      )} n chains along [001]. One of the three tetra-methyl-ethylendi-ammonium cations
      is disordered and was refined using a split model (occupancy ratio 0.58:0.42).
      The cations and the water mol-ecule are connected to the {[Sb2Br10](4-)} n
      polymeric anions by weak N-H ?Br and O(water)-H ?Br hydrogen bonding. 

PMID- 24454157
TI  - (3-Methyl-benzo-nitrile-kappaN)tetra-kis(MU-N-phenyl-acetamidato)-kappa(4)
      N:O;kappa(4) O:N-di-rhodium(II)(Rh-Rh).
AB  - In the title compound, [Rh2(C8H8NO)4(C8H7N)], the four acetamidate ligands
      bridging the dirhodium core are arranged in a 2,2-trans manner. One Rh(II) atom
      is five-coordinate, in a distorted pyramidal geometry, while the other is six
      coord-in-ate, with a disorted octa-hedral geometry. For the six-coord-inate
      Rh(II) atom, the axial nitrile ligand shows a non-linear Rh-nitrile coordination
      with an Rh-N-C bond angle of 166.4 (4) degrees  and a nitrile N-C bond length of
      1.138 (6) A. Each unique Rh(II) atom is coordinated by a trans pair of N atoms
      and a trans pair of O atoms from the four acetamide ligands. The Neq-Rh-Rh-Oeq
      torsion angles on the acetamide bridge varies between 12.55 (11) and 14.04 (8)
      degrees . In the crystal, the 3-methyl-benzo-nitrile ring shows a pi-pi inter
      action with an inversion-related equivalent [inter-planar spacing = 3.360 (6) A].
      A phenyl ring on one of the acetamide ligands also has a face-to-face pi-pi inter
      action with an inversion-related equivalent [inter-planar spacing = 3.416 (5) A].

PMID- 24454158
TI  - Bis(2,2'-bipyridine)[1,9-bis(diphenylphos-phanyl)-1,2,3,4,6,7,8,9-octahydropyrim
      ido[1,2-a]pyrimidin-5-ium]ruthenium(II) hexa-fluorido-phosphate dibromide di
      chloro-methane disolvate monohydrate.
AB  - In the cation of the title complex,
      [Ru(C31H32N3P2)(C10H8N2)2](PF6)(Br)2.2CH2Cl2.H2O, the ruthenium ion is
      coordinated in a distorted octa-hedral geometry by two 2,2'-bi-pyridine (bpy)
      ligands and a chelating cationic N-di-phenyl-phosphino-1,3,4,6,7,8-hexa-hydro-2
      pyrimido[1,2-a]pyrimidine [(PPh2)2-hpp] ligand. The tricationic charge of the
      complex is balanced by two bromide and one hexa-fluorido-phosphate counter
      anions. The compound crystallized with two mol-ecules of di-chloro-methane (one
      of which is equally disordered about a Cl atom) and a water mol-ecule. In the
      crystal, one of the Br anions bridges two water mol-ecules via O-H?Br hydrogen
      bonds, forming a centrosymmetric diamond-shaped R (4) 2(8) motif. The cation and
      anions and the solvent mol-ecules are linked via C-H?F, C-H?Br, C-H?Cl and C-H?O
      hydrogen bonds, forming a three-dimensional network. 

PMID- 24454159
TI  - N,N,N',N'-Tetra-methyl-ethylene-diammonium tetra-chlorido-zincate.
AB  - The asymmetric unit of the title compound, (C6H18N2)[ZnCl4], consists of one
      tetra-chlorido-zincate anion and two half-N,N,N'N'-tetra-methyl-ethylenedi
      ammonium cations. Each of the two di-ammonium cations is located about an
      inversion center and one of them is disordered over two sets of sites in a 0.780
      (17):0.220 (17) ratio. The Zn(II) atom has a slightly distorted tetra-hedral
      coordination environment. The cations and anions are connected via N-H?Cl
      hydrogen bonds into chains extending along [0-11]. 

PMID- 24454160
TI  - Hexa-MU-acetato-1:2kappa(4) O,O';1:2kappa(2) O:O;2:3kappa(4) O,O';2:3kappa(2) O:O
      bis-(4,4'-dimethyl-2,2'-bi-pyridine)-1kappa(2) N,N';3kappa(2) N,N'-2-calcium-1,3
      dizinc.
AB  - In the centrosymmetric trinuclear Zn(II)?Ca(II)?Zn(II) title complex,
      [CaZn2(CH3COO)6(C12H12N2)2], the Ca(II) ion lies on an inversion centre and is
      octa-hedrally coordinated by six acetate O atoms. The Zn(II) ion is coordinated
      by two N atoms from a bidentate di-methyl-bipyridine ligand and three O atoms
      from acetate ligands bridging to the Ca(II) ion, leading to a distorted square
      pyramidal coordination sphere. The Zn?Ca distance is 3.4668 (5) A. 

PMID- 24454161
TI  - Bis(5-amino-1H-tetra-zole-kappaN (4))di-aqua-(oxalato-kappa(2) O (1),O
      (2))cadmium.
AB  - In the monomeric title complex, [Cd(C2O4)(CH3N5)2(H2O)2], the Cd(II) ion exhibits
      a distorted octa-hedral coordination geometry, with the equatorial plane defined
      by two O atoms from an oxalate ligand and two N atoms from two 5-amino-1H-tetra
      zole ligands; the axial sites are occupied by two water mol-ecules, with longer
      Cd-O bond lengths. An intra-molecular N-H?O hydrogen bond occurs. In the crystal,
      N-H?O as well as O-H?O and O-H?N hydrogen bonds (some of which are bifurcated)
      link the complex mol-ecules into a three-dimensional network. 

PMID- 24454162
TI  - Poly[[(MU2-4,4'-bipyridyl-kappa(2) N:N')bis-{MU2-N-[2-(2-hy-droxy-benzo
      yl)carbamo-thio-yl]acetamidato-kappa(4) O,N,O':S}bis-(nitrato-kappa(2)
      O,O')dicadmium] di-methyl-formamide tetra-solvate].
AB  - The asymmetric unit of the title complex,
      {[Cd2(C10H10N3O3S)2(C10H8N2)(NO3)2].4C3H7NO} n , consists of one Cd(II) cation,
      one N-[2-(2-hy-droxy-benzo-yl)carbamo-thio-yl]acetamidate ligand, half a 4,4'
      bipyridyl ligand, one coordinating nitrate anion and two di-methyl-formamide
      solvent mol-ecules of crystallization. The bipyridine ligand is completed by
      inversion symmetry. The metal cation exhibits a distorted penta-gonal-bipyramidal
      coordination geometry provided by two O and one N atoms of the thio-semicarbazide
      ligand, two O atoms of the nitrate anion, one S atom of a neighbouring thio
      semicarbazide ligand and one 4,4'-bi-pyridine N atom. The bridging role of the
      thio-semicarbazide ligand through the S atom leads to centrosymmetric binuclear
      units, which are further linked by 4,4'-bi-pyridine units, forming polymeric
      chains extending along the b-axis direction. An intra-molecular N-H?O hydrogen
      bond occurs. The crystal structure also features N-H?O and O-H?O hydrogen bonds,
      leading to the formation of a three-dimensional network. 

PMID- 24454163
TI  - Tetra-aqua-bis-(piperazin-1-ium)cobalt(II) bis-(sulfate) dihydrate.
AB  - In the centrosymmetric title compound, [Co(C4H11N2)2(H2O)4](SO4)2.2H2O, the
      Co(II) atom is coordinated in a distorted octa-hedral geometry by four water O
      atoms and two piperazinium N atoms. These four water O atoms define an equatorial
      plane with a maximum deviation of 0.0384 (1) A while the two piperazinium N atoms
      complete the octa-hedron in the axial positions. Neighboring complex mol-ecules
      and sulfate anions are connected through an extensive network of N-H?O and O-H?O
      hydrogen bonds, which link the different chemical species into layers in the ab
      plane. Additional Owater-H?O hydrogen bonds involving the non-coordinating water
      mol-ecules and C-H?O inter-actions connect these layers into a three-dimensional
      supra-molecular structure. 

PMID- 24454164
TI  - (MU3-Hydrido)[MU3-2-(tri-methyl-sil-yl)ethyl-idyne-kappa(3) C (1):C (1):C
      (1)]tetra-kis-[(eta(5)-cyclo-penta-dien-yl)cobalt(II)].
AB  - In the title compound, [Co4(C5H5)4(MU3-CCH2SiMe3)(MU3-H)], the Co atoms form a
      distorted tetra-hedron with the ethyl-idyne moiety bridging three of the Co atoms
      as well as the hydrido ligand also bridging three of the Co atoms. The Co-Co bond
      lengths in the Co4 tetrahedron vary from 2.3844 (4) to 2.4608 (4) A. Each Co atom
      is additionally eta(5)-bonded to a cyclopentadienyl (Cp) anion. 

PMID- 24454165
TI  - [meso-5,10,15,20-Tetra-kis(3-methyl-thio-phen-2-yl)porphyrinato-kappa(4)
      N,N',N'',N''']nickel(II) benzene hemisolvate.
AB  - In the title compound, [Ni(C40H28N4S4)].0.5C6H6, the Ni(II) atom is in a square
      planar geometry defined by four pyrrole N atoms. There is considerable buckling
      in the porphyrin ring with the dihedral angles between the N4 donor set and the
      pyrrole rings being in the range 16.24 (5)-22.47 (5) degrees . Each of the six
      membered chelate rings is twisted about an Ni-N bond and the dihedral angles
      between diagonally opposite chelate rings are 21.36 (4) and 23.87 (4) degrees ;
      each pair of rings is oriented in opposite directions. The methyl-thienyl rings
      are twisted out of the plane of the central N4 core with dihedral angles in the
      range 75.98 (2)-88.70 (5) degrees . All four methyl-thienyl groups are disordered
      over two sets of sites, as is commonly found with such groups, with occupancies
      of 0.553 (8):0.447 (8), 0.579 (7):0.421 (7), 0.796 (6):0.204 (6) and 0.956
      (7):0.044 (7). The benzene solvent mol-ecule was found to be present in half
      occupancy. 

PMID- 24454166
TI  - Tetra-chlorido-[N (2),N (2')-(di-methyl-silanedi-yl)bis-(N-tert-butyl-3-methyl
      benzimid-amid-ato)-kappa(2) N (2),N (2')]hafnium(IV).
AB  - The symmetric title mol-ecule, [Hf(C26H40N4Si)Cl4], lies about a twofold rotation
      axis. The Hf(IV) and Si atoms lie on the rotation axis with all other atoms being
      in general positions. The Hf(IV) atom is six-coordinated by two N atoms from the
      N (2),N (2')-(di-methyl-silanedi-yl)bis-(N-tert-butyl-3-methyl-benz-imid-amidate)
      ligand and four Cl(-) ions in a slightly distorted octa-hedral geometry. The two
      amidinate moieties are connected through the central Si atom with Si-N bond
      length of 1.762 (3) A, generating the characteristic N-C-N-Si-N-C-N skeleton of a
      silyl-linked ansa-bis-(amidine) species. 

PMID- 24454167
TI  - catena-Poly[[aqua-lithium(I)]-MU-3-carb-oxy-5,6-di-methyl-pyrazine-2-carboxyl-ato
      kappa(4) O (2),N (1):O (3),N (4)].
AB  - The asymmetric unit of the title compound, [Li(C8H6N2O4)(H2O)] n , comprises
      three Li cations, two of which are located on a twofold rotation axis, two
      carboxylate anions and three water mol-ecules, of which two are situated on the
      twofold rotation axis being aqua ligands. Both carboxylate anions are in MU2
      bridging mode. All Li ions show a trigonal-bipyramidal coordination mode; the two
      located in special positions are bridged through N,O-bonding sites generating a
      polymeric ribbon along the c-axis direction. The Li cation in a general position
      creates an independent polymeric ribbon through N,O-bonding sites of the two
      symmetry-related ligands; the trigonal-bipyramidal coordination is completed by
      an aqua ligand. In both carboxylate anions, a carboxyl-ate and a carb-oxy-lic
      acid group form an intra-molecular hydrogen bond. The polymeric ribbons running
      along [001] are inter-connected by hydrogen bonds in which the water mol-ecules
      act as donors and carboxyl-ate O atoms act as acceptors, giving rise to a three
      dimensional architecture. 

PMID- 24454168
TI  - Bis(acetyl-acetonato-kappa(2) O,O')(pyridine-kappaN)(thio-cyanato
      kappaN)manganese(III): a redetermination using data from a single crystal.
AB  - In the crystal structure of the title compound, [Mn(C5H7O2)2(NCS)(C5H5N)], the
      Mn(3+) cation is coordin-ated by two acetyl-acetonate anions, one terminal thio
      cyanate anion and one pyridine ligand within a slightly distorted octa-hedron.
      The asymmetric unit consists of half a complex mol-ecule with the Mn(3+) cation,
      the thio-cyanate anion and the pyridine ligand located on a mirror plane. The
      acetyl-acetonate anion is in a general position. The title compound was
      previously described [Stults et al. (1975 ?). Inorg. Chem. 14, 722-730] but could
      only be obtained as a powder. Suitable crystals have now been obtained for a high
      precision single-crystal structure determination. 

PMID- 24454169
TI  - [MU2-N (2),N (2')-Bis(3-meth-oxy-2-oxido-benzyl-idene)benzene-1,3-dicarbo-hydrazi
      dato]bis-[pyridine-copper(II)].
AB  - In the centrosymmetric dinuclear title complex, [Cu2(C24H18N4O6)(C5H5N)2], the
      Cu(II) ions is tetra-coordinated by two O-atoms and one N-donor of the bridging
      terephthalo-hydra-zonate ligand and by one pyridine N atom, resulting in a nearly
      square-planar N2O2 coordination geometry with the Cu(II) ion 0.044 (2) A out of
      the mean plane (r.m.s. deviation of 0.0675 A) of the coordinating atoms. 

PMID- 24454170
TI  - Chlorido(eta(6)-N (2)-diphenylphosphanyl-N (1),N (1)-diisopropyl-4-methoxybenz
      amidine-kappaP)(triphenylphosphane-kappaP)ruthenium(II) trifluoromethansulfonate
      acetone disolvate.
AB  - In the title compound, [RuCl(C18H15P)(C26H31N2OP)](CF3O3S).2C3H6O, the Ru(II) ion
      is coordinated in a three-legged piano stool, half-sandwich-type geometry by a
      chlorido ligand, a tri-phenyl-phosphine and a tethered eta(6)-(phenyl-p-O-meth
      oxy) kappa(1)-P N-di-phenyl-phosphino N'-diisopropyl amidine ligand charge
      balanced by a trifluormethansulfonate counter-anion. The eta(6)-coordination mode
      of the arene incorporated into the structure was generated in situ after addition
      of methyl tri-fluoro-methane-sulfonate to the neutral eta(5)-arene tethered
      precursor complex [RuCl(PPh3)(eta(5):kappa(1)-OC6H4C(NiPr2)=N-PPh2)] in di-chloro
      methane solution. 

PMID- 24454171
TI  - Bis(4-amino-pyridinium) MU6-oxido-dodeca-MU2-oxido
      hexaoxido[rhenium(VII)tetratungsten(VI)vanadium(V)]ate hepta-hydrate.
AB  - In the title organic-inorganic hybrid compound, (C5H7N2)2[ReVW4O19].7H2O, the
      Lindqvist-type polyoxido anion has crystallographically imposed mm2 symmetry and
      is built up by six MO6 (M = W, V, Re) edge-sharing distorted octa-hedra. The Re
      and V atoms share the same crystallographic site in a 0.5:0.5 ratio. The 4-amino
      pyridinium cations lie on a mirror plane. Three of the four independent water O
      atoms in the asymmetric unit are located on a mirror plane whereas the remaining
      O atom has mm2 site symmetry. In the crystal, the cations, anions and water mol
      ecules are linked into a three-dimensional network through O-H?O and N-H?O
      hydrogen-bonding inter-actions. 

PMID- 24454172
TI  - Bis(5-hy-droxy-isophthalato-kappaO (1))bis-[4-(pyridine-3-carboxamido-kappaN
      (3))pyridinium]copper(II) tetra-hydrate.
AB  - In the title compound, [Cu(C11H10N3O)2(C8H4O5)2].4H2O, the Cu(II) ion, located on
      a crystallographic inversion center, is coordinated in a square-planar
      environment by two trans-O atoms belonging to two monodentate 5-hy-droxy
      isophthalate (hip) dianions and two trans nicotinamide pyridyl N-donor atoms from
      monodentate protonated pendant N-(pyridin-4-yl)nicotinamide (4-pnaH) ligands. The
      protonated 4-pyridyl-amine groups engage in N-H(+)?O(-) hydrogen-bond donation to
      unligated hip O atoms to construct supra-molecular chain motifs parallel to
      [100]. Water mol-ecules of crystallization, situated between the chains, engage
      in O-H?O hydrogen bonding to form supra-molecular layers and the overall three
      dimensional network structure. 

PMID- 24454173
TI  - Poly[MU3-aqua-aqua-MU5-(4-nitro-benzoato)-caesium].
AB  - In the structure of the title complex, [Cs(C7H4NO2)(H2O)2] n , the caesium salt
      of 4-nitro-benzoic acid, the irregular CsO9 coordination sphere comprises three
      bridging nitro O-atom donors, a bidentate carboxyl-ate O,O'-chelate inter-action,
      a triple-bridging water mol-ecule and a monodentate water mol-ecule. A three
      dimensional framework polymer is generated, within which there are water-carboxyl
      ate O-H?O and water-water O-H?O hydrogen-bonding inter-actions. 

PMID- 24454174
TI  - Bis(3-aza-niumylprop-yl)aza-nium hexa-chlorido-bis-muthate(III) monohydrate.
AB  - The asymmetric unit of the title compound, (C6H20N3)[BiCl6].H2O, consists of a
      triprotonated bis-(3-aza-niumylprop-yl)aza-nium cation, two halves of an
      octahedral [BiCl6](3-) anion, each of the Bi(III) atoms lying on an inversion
      centre, and a water mol-ecule. In the crystal, the anions and water mol-ecules
      are linked by O-H?Cl hydrogen bonds, forming chains running parallel to [0-11].
      The anionic chains and the cations are further linked into a three-dimensional
      network by N-H?Cl and N-H?O hydrogen-bond inter-actions. 

PMID- 24454175
TI  - Imidazolium trans-di-aqua-dioxalato-chromate(III) dihydrate.
AB  - In the title hydrated mol-ecular salt, (C3H5N2)[Cr(C2O4)2(H2O)2].2H2O, the
      complete cation is generated by a crystallographic twofold rotation axis, with
      one C atom lying on the rotation axis. The complete anion is generated by
      crystallographic inversion symmetry (Cr(III) site symmetry -1), to generate a
      slightly distorted CrO6 octa-hedron with trans water mol-ecules and chelating
      oxalate dianions. The oxalate ion is almost planar (r.m.s. deviation = 0.017 A)
      and the five-membered chelate ring is a shallow envelope with the metal ion
      displaced by 0.126 (1) A from the ligand atoms. The crystal structure features O
      H?O, N-H?O and C-H?O hydrogen bonds, which link the components into a three
      dimensional network. 

PMID- 24454176
TI  - 2-[(Ferrocen-1-yl)(hy-droxy)meth-yl]prop-2-ene-nitrile.
AB  - In the title ferrocene derivative, [Fe(C5H5)(C9H8NO)], the dihedral angle between
      the ene-nitrile group and the substituted cyclo-penta-dienyl ring is 71.2 (1)
      degrees . The cyclopentadienyl rings of the ferrocene moiety are arranged in an
      eclipsed conformation. The hy-droxy group, and the corresponding methine H atom,
      are disordered over two sets of sites with site-occupancy factors of 0.744 (4)
      and 0.256 (4). An intra-molecular C-H?O close contact is observed. In the
      crystal, O-H?N hydrogen bonds form a C(6) chain along [100]. 

PMID- 24454177
TI  - Poly[bis-(MU2-1,3-phenyl-enedi-amine-kappa(2) N:N')di-MU-thio-cyanato-kappa(2)
      N:S;kappa(2) S:N-cadmium].
AB  - The structure of the title polymeric compound, [Cd(SCN)2(C6H8N2)2] n , exhibits a
      two-dimensional staircase-like structure parallel to (010) in which the Cd(II)
      atom lies on a twofold rotation axis and has a distorted octa-hedral CdS2N4
      geometry involving four MU-1,3-(SCN) group donors and two N-atom donors from 1,3
      phenyl-enedi-amine ligands, which also have twofold symmetry. The major
      contributions to the cohesion and the stability of this two-dimensional polymeric
      structure are the covalent Cd-S,N bonds and one weak intra-layer N-H?S hydrogen
      bond. 

PMID- 24454178
TI  - Poly[di-MU9-citrato-tetra-sodiumzinc].
AB  - In the title compound, [Na4Zn(C6H5O7)2] n , the Zn(II) ion lies on an inversion
      center and is coordinated by six O atoms from two citrate ligands, forming a
      distorted octa-hedral geometry. There are two crystallographically independent
      Na(+) cations in the asymmetric unit. One Na(+) cation exhibits a distorted
      square-pyramidal geometry defined by five O atoms from four citrate ligands. The
      other Na(+) cation is surrounded by six O atoms from five citrate ligands in a
      distorted octa-hedral geometry. The Na(+) cations are bridged by citrate carboxyl
      ate groups, forming a layer parallel to (100). The layers are further assembled
      into a three-dimensional network with the [Zn(citrate)2](4-) building units as
      'pillars'; O-H?O hydrogen bonds also stabilize the structure. 

PMID- 24454179
TI  - [6,6'-Bis(1,1-di-methyl-eth-yl)-4,4'-dimethyl-2,2'-methyl-enediphenolato-kappa(2)
      O,O']di-chlorido-(9H-fluoren-9-ol-kappaO)titanium(IV)-fluorene-diethyl ether
      (1/0.5/1).
AB  - The title adduct, [TiCl2(C23H30O2)(C13H10O].0.5C13H10.C4H10O, is a monomer with a
      trigonal-bypyramidal coordination sphere of the Ti(IV) atom in which the ligand O
      atoms of the bidentate diphenolate anion are located in both apical and
      equatorial positions. Chloride ligands occupy the remaining two equatorial sites
      of the trigonal bypyramid with the fluoren-9-ol O atom occupying the other apical
      site. The hy-droxy group H atom of this latter group is hydrogen bonded to an O
      atom of a non-coordinating diethyl ether mol-ecule. The title compound also
      contains a further fluorene solvent mol-ecule, which lies across a centre of
      symmetry and which is equally disordered over an inversion centre. 

PMID- 24454180
TI  - Di-n-but-yl[4-hy-droxy-N'-(3-meth-oxy-2-oxido-benzyl-idene-kappaO (2))benzo
      hydrazidato-kappa(2) N,O]tin(IV).
AB  - In the title compound, [Sn(C4H9)2(C15H12N2O4)], the Sn(IV) atom is coordinated by
      the N, O and O' atoms from the tridentate Schiff base dianion in an overall cis
      C2SnNO2 trigonal-bipyramidal geometry. Adjacent mol-ecules are linked by O-H?O
      hydrogen bonds, forming a chain running along [001]. 

PMID- 24454181
TI  - Bis(MU-2-hy-droxy-methyl-2-methyl-propane-1,3-diolato)bis-[di-chlorido
      titanium(IV)] diethyl ether disolvate.
AB  - The title complex, [Ti2Cl4{CH3C(CH2O)2(CH2OH)}2], lies across a centre of
      symmetry with a diethyl ether solvent mol-ecule hydrogen bonded to the -CH2OH
      groups on either side of it. The Ti(IV) atom is coordinated in a distorted octa
      hedral geometry by a tripodal ligand and two terminal chloride atoms. There are
      three coordination modes for the tripodal ligand distinguishable on the basis of
      their very different Ti-O bond lengths. For the terminal alkoxo ligand, the Ti-O
      distance is 1.760 (1) A, the asymmetric bridge system has Ti-O bond lengths of
      1.911 (1) and 2.048 (1) A. The Ti-O bond length for the alcohol O atom is the
      longest at 2.148 (1) A. 

PMID- 24454182
TI  - Bis(2-meth-oxy-anilinium) hexa-bromido-stannate(IV) dihydrate.
AB  - The asymmetric unit of the title compound, (C7H10NO)2[SnBr6].2H2O, contains one
      cation, one half-dianion and one lattice water mol-ecule. The [SnBr6](2-)
      dianion, located on an inversion center, exhibits a highly distorted octa-hedral
      coordination environment, with Sn-Br bond lengths ranging from 2.2426 (9) to
      3.0886 (13) A. In the crystal, O-H?Br, N-H?Br, N-H?O and C-H?Br hydrogen bonds
      consolidate the packing, which can be described as consisting of alternating
      anionic (containing dianions and lattice water mol-ecules) and cationic layers
      parallel to ab plane. 

PMID- 24454183
TI  - Poly[[octaaqua-MU4-(benzene-1,2,4,5-tetra-carboxyl-ato)-dicobalt(II)] octa
      hydrate].
AB  - The title polymeric coordination compound, {[Co2(C10H2O8)(H2O)8].8H2O} n , was
      obtained by slow diffusion of a dilute aqueous solution of CoCl2 and the sodium
      salt of benzene-1,2,4,5-tetracarboxylic acid (H4btec) through an agar-agar gel
      bridge in a U-shaped tube. The two independent Co(2+) ions are each situated on
      an inversion centre and are coordinated in a slightly distorted octa-hedral
      geometry by four water O atoms and two carboxyl-ate O atoms from two btec(4-)
      ligands (-1> symmetry), forming a layer parallel to (11-1). This layer can be
      described as a mol-ecular two-dimensional square grid with the benzene rings at
      the nodes and the Co(II) atoms connecting the nodes. O-H?O hydrogen-bonding
      interactions involving the coordinating water molecules, the carboxylate O atoms
      and lattice water molecules lead to the formation of a three-dimensional network.

PMID- 24454184
TI  - Bis{MU4-N-[phen-yl(pyridin-2-yl-aza-nid-yl)meth-yl]pyridin-2-aminido}tetra
      kis(tetra-hydro-furan)-tetra-lithium.
AB  - The title complex, [Li4(C17H14N4)2(C4H8O)4], bears a novel tetra-dentate di-amido
      ligand. In the tetra-nuclear centrosymmetric complex mol-ecule, the metal atoms
      exhibit two kinds of coordination modes. The middle two Li(+) cations are coord
      inated by four N (ligand) and one O (tetra-hydro-furan, THF) atoms, resulting in
      a distorted square-pyramidal geometry. The outer two Li(+) cations are in
      distorted tetra-hedral environments consisting of three N (ligand) and one O
      (THF) atoms. The Li-N bond lengths vary from 2.020 (7) to 2.441 (6)A. 

PMID- 24454185
TI  - Bis(2,9-dimethyl-1,10-phenanthroline)copper(I) penta-cyanido-nitro-soferrate(II).
AB  - The asymmetric unit of the title complex [Cu(C14H12N2)2]2[Fe(CN)5(NO)], consists
      of a [Cu(dmp)2](+) cation (dmp is 2,9-dimethyl-1,10-phenanthroline) and half an
      [Fe(CN)5(NO)](2-) anion. The anion is disordered across an inversion center with
      the Fe(II) ion slightly offset (ca 0.205A) from the inversion center in the
      direction of the disordered trans-coordinating CN/NO ligands. The anion has a
      distorted octa-hedral coordination geometry. The Cu(I) ion is coordinated by two
      phenanthroline ligands in a distorted tetra-hedral geometry. The dihedral angle
      between the phenanthroline ligands is 77.16 (4) A. In the crystal, the cations
      are connected to the anions by weak C-H?N hydrogen bonds. In addition, weak pi-pi
      stacking inter-actions are observed, with centroid-centroid distances in the
      range 3.512 (3)-3.859 (3) A. 

PMID- 24454186
TI  - Di-MU-oxido-bis-[bis-(diiso-propyl-aceta-midinato)-kappaN;kappa(2) N,N'
      germanium(IV)].
AB  - The title compound, [Ge2(C8H17N2)4O2], crystallizes with imposed twofold
      symmetry, which allows the monodentate amidinate ligands to be arranged in a
      cisoid fashion. The independent Ge-O distances within the central Ge2O2 ring,
      which is essentially planar (r.m.s. deviation = 0.039 A), are 1.7797 (8) and
      1.8568 (8) A. The germanium centres adopt a distorted trigonal-bipyramidal
      geometry, being coordinated by the two O atoms and by one bidentate and one
      monodentate amidinate ligand (three N atoms). One N-isopropyl group is disordered
      over two positions; these are mutually exclusive because of 'collisions' between
      symmetry-equivalent methyl groups and thus each has 0.5 occupancy. 

PMID- 24454187
TI  - {4-Chloro-N'-[(2-oxidonaphthalen-1-yl-kappaO)methyl-idene]benzohydrazidato
      kappa(2) N',O}di-methyl-tin(IV).
AB  - In the title complex, [Sn(CH3)2(C18H11ClN2O2)], the Sn(IV) ion is coordinated by
      two O atoms and an N atom from a 4-chloro-N'-[(2-oxidonaphthalen-1-yl)methyl
      idene]benzohydrazidate ligand and two C atoms from two methyl ligands in a
      distorted trigonal-bipyramidal geometry [Sn-O = 2.092 (3) and 2.144 (3) A; Sn-N =
      2.160 (4) A]. The dihedral angle between the naphthalene ring system and the
      benzene ring is 8.6 (2) degrees . In the crystal, adjacent mol-ecules are linked
      by weak C-H?O hydrogen bonds, forming a chain along the b-axis direction. 

PMID- 24454188
TI  - catena-Poly[[tetra-MU-formato-kappa(8) O:O'-dicopper(II)]-MU-hexa-methyl-ene
      tetra-mine-kappa(2) N (1):N (5)].
AB  - In the title polymeric compound, [Cu2(HCO2)4(C6H12N4)] n , the Cu(II) atom is
      five-coordinated in a square-pyramidal geometry that is defined by four O atoms
      from four formate ligands and one N atom from a hexa-methyl-ene-tetra-mine
      ligand. The two Cu(II) atoms are separated by 2.6850 (7) A, and together with the
      four formate ligands they form a paddle-wheel unit. The hexa-mine ligand uses
      only two of its four N atoms to link Cu2 cluster units, affording a zigzag chain
      running along the b-axis direction. The hexa-mine ligand lies on a mirror plane. 

PMID- 24454189
TI  - N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-di-hydro-1H-pyrazol-4-yl)-2-phenyl-acetamide.
AB  - The title compound, C19H19N3O2, crystallizes with two independent mol-ecules (A
      and B) in the asymmetric unit. In mol-ecule A, the pyrazole ring adopts a
      slightly disordered half-chair conformation while in B it is planar [r.m.s.
      deviation = 0.0386 (15) A]. The dihedral angle between the mean planes of the two
      phenyl rings is 56.2 (8) in A and 38.2 (3) degrees  in B. The N-phenyl
      substituent on the pyrazole ring is twisted by 46.5 (2) in A and 58.6 (4) degrees
      in B while the extended phenyl ring is twisted by 82.2 (8) in A and 87.5 (9)
      degrees  in B. The mean plane of the amide group forms an angle of 74.8 (3) in A
      and 67.7 (1) degrees  in B with respect to the phenyl ring. In addition, the
      amide group is rotated by 51.4 (1) in A and 53.6 (2) degrees  in B from the the
      mean plane of the pyrazole ring. In the crystal, the two molecules are linked via
      N-H?O hydrogen bonds, supported by weak C-H?O inter-actions, forming dimers
      enclosing an R 2 (2)(10) ring motif. The dimers are linked via C-H?O inter
      actions, forming a three-dimensional structure. 

PMID- 24454190
TI  - 4-Eth-oxy-3-meth-oxy-benzaldehyde.
AB  - In the title compound, C10H12O3, all non-H atoms are approximately coplanar, with
      an r.m.s. deviation of 0.046 A. In the crystal, very weak C-H?O inter-actions
      link the mol-ecules into sheets parallel to (101). 

PMID- 24454191
TI  - 2-Bromo-3-hy-droxy-6-methyl-pyridine.
AB  - In the title compound, C6H6BrNO, the Br atom is displaced from the pyridine ring
      mean plane by 0.0948 (3) A, while the hydroxyl O atom and the methyl C atom are
      displaced by 0.0173 (19) and 0.015 (3) A, respectively. In the crystal, mol
      ecules are linked via O-H?N hydrogen bonds, forming chains propagating along the
      a-axis direction. These chains are linked by C-H?Br hydrogen bonds, forming
      corrugated two-dimensional networks lying parallel to the ac plane. 

PMID- 24454192
TI  - Ethyl 2-[6-(4-methyl-benzo-yl)-7-phenyl-2,3-di-hydro-1H-pyrrolizin-5-yl]-2-oxo
      acetate.
AB  - In the title compound, C25H23NO4, the pyrrolizine ring is approximately planar
      with an r.m.s deviation from planarity of 0.0053 A, while the fused di-hydro
      pyrrolizine ring adopts an envelope conformation with the C atom connected to two
      CH2 as the flap. The dihedral angles between the fused ring system and the phenyl
      and methyl-benzoyl rings are 41.65 (11) and 66.30 (8) degrees , respectively. In
      the crystal, weak C-H?O hydrogen bonds and C-H?pi inter-actions occur. One mol
      ecule is linked to five adjacent ones through eight hydrogen bonds, forming a
      three-dimensional network. 

PMID- 24454193
TI  - 5-Bromo-benzene-1,3-dicarbo-nitrile.
AB  - The asymmetric unit of the title compound, C8H3BrN2, consists of two mol-ecules.
      The crystal structure features undulating mol-ecular sheets with the mol-ecules
      linked by C-H?N hydrogen bonds with one N atom acting as a bifurcated acceptor.
      N?Br inter-actions also occur [N?Br = 2.991 (3) and 3.099 (3) A]. Inter-layer
      association is accomplished by offset face-to-face arene inter-actions [centroid
      centroid distance = 3.768 (4) A]. 

PMID- 24454194
TI  - 13-(Imidazol-1-yl)-11,13-di-hydro-melampomagnolide B monohydrate.
AB  - The title compound, C18H24N2O4.H2O {systematic name: (1aR,7aS,8R,10aS,10bS,E)-5
      hy-droxy-methyl-8-[(1H-imidazol-1-yl)meth-yl]-1a-methyl-2,3,6,7,7a,8,10a,10b-octa
      hydro-oxireno[2',3':9,10]cyclo-deca-[1,2-b]furan-9(1aH)-one monohydrate}, an
      imidazole derivative of melampomagnolide B was synthesized under Michael addition
      conditions. The mol-ecule is built up from fused ten-, five- (lactone) and three
      membered (epoxide) rings. The inter-nal double bond of the ten-membered ring
      identifies it as the cis or E isomer. The lactone ring has an envelope-type
      conformation, with the (chiral) C atom opposite the lactone O atoms as the flap
      atom. In the crystal, O-H?O, O-H?N and weak C-H?O hydrogen bonds link the mol
      ecules (along with water) into sheets parallel to the bc plane. 

PMID- 24454195
TI  - 5-Methyl-1,3-diphenyl-N-(5-phenyl-1,3,4-thia-diazol-2-yl)-1H-pyrazole-4
      carboxamide.
AB  - The asymmetric unit of the title compound C25H19N5OS, contains two mol-ecules, A
      and B. In mol-ecule A, the dihedral angles between the pyrazole ring and the C
      bound phenyl group, the N-bound phenyl group and the thia-diazole ring are 32.30
      (14), 52.25 (14) and 34.94 (12) degrees , respectively. The corresponding angles
      in mol-ecule B are 33.32 (14), 50.67 (15), and 70.30 (12) degrees , respectively.
      In the crystal, the A and B mol-ecules are linked by pairs of N-H?N hydrogen
      bonds, generating R 2 (2)(8) loops. This dimer linkage is reinforced by two C-H?O
      hydrogen bonds and one C-H?N hydrogen bond. 

PMID- 24454196
TI  - Venlafaxine besylate monohydrate.
AB  - The title compound {systematic name: [2-(1-hydroxycyclohexyl)-2-(4
      methoxyphenyl)ethyl]dimethylazanium benzene-sulfonate monohydrate}, C17H28NO2
      (+).C6H5O3S(-).H2O, is a besylate salt hydrate of the anti-depressant drug
      venlafaxine. In the crystal, besylate anions and water mol-ecules self-assemble,
      forming hydrogen-bonded dimers linked around inversion centers, with graph set R
      4 (4)(6). The crystal packing features a chain of alternate dimers and
      venlafaxine cations in the b-axis direction with the components linked by O-H?O
      hydrogen bonds and C-H?O and C-H?pi inter-actions. This is the first example of a
      venlafaxine cation with a closed conformation, as it features an intra-molecular
      N-H?O inter-action involving the protonated N atom. 

PMID- 24454197
TI  - N (1)-(Thio-phen-2-ylmeth-yl)-N (3),N (3)-bis-[3-(thio-phen-2-yl-methyl-ammonio)
      prop-yl]propane-1,3-di-ammonium hexa-fluorido-silicate methanol tris-olvate.
AB  - In the title compound, C24H40N4S3 (4+).2SiF6 (2-).3CH3OH, the central tertiary
      amine function is protonated and is connected to three thio-phen-2-yl-methyl
      amino-n-propyl groups, forming the arms of a T-shaped cation that has two
      pockets. Each arm contains one protonated secondary amine function, and each
      pocket is occupied by one SiF6 (2-) anion bonded via two N-H?F inter-actions with
      the protonated amine group on the middle arm, while two methanol solvent mol
      ecules are N-H?O hydrogen-bonded with the other secondary protonated amine groups
      on the side arms. Weak O-H?O and O-H?F hydrogen bonds between the solvent mol
      ecules and between the solvent mol-ecules and the anions, respectively, are also
      observed. All three thio-phene groups in the arms are disordered over two sets of
      sites, with occupancy ratios of 0.828 (3):0.172 (3), 0.910 (2):0.090 (2) and
      0.890 (3):0.110 (3). 

PMID- 24454198
TI  - N-Benzyl-2-hy-droxy-ethanaminium cyanurate.
AB  - In the cation of the title compound C9H14ON(+).C3H2O3N3 (-), the benzyl-amine C-N
      bond subtends a dihedral angle of 78.3 (2) degrees  with the phenyl ring. The
      cyanurate anion is in the usual keto-form and shows an r.m.s. deviation from
      planarity of 0.010 A. In the crystal, the cyanurate anions form N-H?O hydrogen
      bonded zigzag ribbons along [001]. These ribbons are crosslinked by the
      organocations via O-H?N and N-H?O hydrogen bonds, forming bilayers parallel to
      (010) which are held together along [010] by slipped pi-pi inter-actions between
      pairs of cyanurate anions [shortest contact distances C?C = 3.479 (2), O?N =
      3.400 (2); centroid-centroid distance= 4.5946 (9) A] and between cyanurate and
      phenyl rings [centroid-centroid distance = 3.7924 (12) A, ring-ring angle = 11.99
      (10) degrees ]. 

PMID- 24454199
TI  - Raltegravir monohydrate.
AB  - THE HYDRATED TITLE COMPOUND [SYSTEMATIC NAME: N-(4-fluoro-benz-yl)-5-hy-droxy-1
      methyl-2-{1-methyl-1-[(5-methyl-1,3,4-oxa-diazol-2-ylcarbon-yl)amino]-eth-yl}-6
      oxo-1,6-di-hydro-pyrimidine-4-carb-oxamide monohydrate], C20H21FN6O5.H2O, is
      recognised as the first HIV integrase inhibitor. In the mol-ecule, the dihedral
      angles between the mean planes of the pyrimidine ring and the phenyl and oxa
      diazole rings are 72.0 (1) and 61.8 (3) degrees , respectively. The mean plane of
      the oxa-diazole ring is twisted by 15.6 (3) degrees  from that of the benzene
      ring, while the mean plane of amide group bound to the oxadiaole ring is twisted
      by 18.8 (3) degrees  from its mean plane. Intra-molecular O-H?O and C-H?N
      hydrogen bonds are observed in the mol-ecule. The crystal packing features O-H?O
      hydrogen bonds, which include bifurcated O-H?(O,O) hydrogen bonds from one H atom
      of the water mol-ecule. In addition, N-H?O hydrogen bonds are observed involving
      the two amide groups. These inter-actions link the mol-ecules into chains along
      [010]. 

PMID- 24454200
TI  - Ethyl N-(3-cyano-1H-indol-2-yl)form-imidate.
AB  - In the title compound, C12H11N3O, the C=N imino bond is in an E conformation. In
      the crystal, adjacent mol-ecules are linked by N-H?Ncyano hydrogen bonds, forming
      a chain running along [110]. 

PMID- 24454201
TI  - 16-Methyl-11-(2-methyl-phen-yl)-14-phenyl-8,12-dioxa-14,15-di-aza-tetra-cyclo
      [8.7.0.0(2,7).0(13,17)]hepta-deca-2(7),3,5,13(17),15-penta-ene-10-carbo-nitrile.
AB  - In the title compound, C28H23N3O2, the pyrazole ring makes a dihedral angle of
      16.90 (6) degrees  with the phenyl ring to which it is attached. Both di-hydro
      pyran rings exhibit half-chair conformations. Intramolecular C-H?O interactions
      generate S(6) and S(8) ring motifs. In the crystal, weak C-H?O and C-H?pi
      interactions occur. 

PMID- 24454202
TI  - 1-Nitro-4-(4-nitro-phen-oxy)benzene: a second monoclinic polymorph.
AB  - In the title compound, C12H8N2O5, the aromatic rings are inclined to one another
      by 56.14 (7) degrees . The nitro groups are inclined by to the benzene rings to
      which they are attached by 3.86 (17) and 9.65 (15) degrees . In the crystal, mol
      ecules are linked by C-H?O hydrogen bonds, forming a three-dimensional structure.
      The title compound is a new monoclinic polymorph, crystallizing in space group
      P21/c. The first polymorph crystallized in space group C2/c and the mol-ecule
      possesses twofold rotation symmetry. Two low-temperature structures of this
      polymorph (150 K and 100 K, respectively) have been reported [Meciarova et al.
      (2004). Private Communication (refcode IXOGAD). CCDC, Cambridge, England, and Dey
      & Desiraju (2005). Chem. Commun. pp. 2486-2488]. 

PMID- 24454203
TI  - 1-(3-Oxo-3-phenyl-prop-yl)piperidinium chloride.
AB  - In the title salt, C14H20NO(+).Cl(-), the piperidine ring adopts a chair
      conformation. In the crystal, the cations and anions are linked by classical N
      H?Cl hydrogen bond and weak C-H?Cl and C-H?O hydrogen bonds; the C-H?O hydrogen
      bonds exhibit R 2 (2)(14) ring motifs while the C-H?Cl hydrogen bonds link the
      mol-ecules into chains along the a-axis direction. pi-pi stacking is observed
      between parallel phenyl rings of adjacent cations, the centroid-centroid distance
      being 3.8164 (15) A. 

PMID- 24454204
TI  - 2,2,2-Tri-fluoro-N-(2-iodo-phen-yl)acetamide.
AB  - The three F atoms in the title compound, C8H5F3INO, are disordered over two sets
      of sites [relative occupancies = 0.615 (14):0.385 (14)]. In the crystal, mol
      ecules are linked by N-H?O hydrogen bonds, forming chains running along the c
      axis direction. The dihedral angle between the ring and the amide group is 62.1
      (3) degrees . 

PMID- 24454205
TI  - N-(4-Acetyl-phen-yl)-4-meth-oxy-benzene-sulfonamide.
AB  - The title compound, C15H15NO4S, was obtained by the condensation of 4-amino-aceto
      phenone and 4-meth-oxy-benzene-sulfonyl chloride. The dihedral angle between the
      benzene rings is 86.56 (9) degrees  and the mol-ecule has an approximate V-shaped
      conformation. The C atom of the meth-oxy group is roughly coplanar with its
      attached ring [deviation = 0.177 (3) A], as is the methyl C atom of the acetyl
      group with its ring [deviation = 0.065 (2) A]. An intra-molecular C-H?O inter
      action generates an S(6) ring. In the crystal, N-H?O and C-H?O hydrogen bonds
      link the mol-ecules into [010] chains. Weak C-H?pi inter-actions are also
      observed. 

PMID- 24454206
TI  - 4-(3-Fluoro-4-methyl-anilino)-2-methyl-idene-4-oxo-butanoic acid.
AB  - The title compound, C12H12FNO3, crystallizes with two independent mol-ecules (A
      and B) in the asymmetric unit. The dihedral angle between the mean planes of the
      3-fluoro-4-methyl-phenyl ring and the oxo-amine group is 25.7 (7) degrees  in mol
      ecule A and 71.3 (7) degrees  in mol-ecule B, while the mean plane of the 2
      methyl-idene-4-oxo-butanoic acid group is twisted by 76.2 (1) degrees  from that
      of the oxo-amine group in mol-ecule A and by 76.2 (4) degrees  in mol-ecule B. In
      the crystal, N-H?O and O-H?O hydrogen bonds [the latter forming an R 2 (2)(8)
      graph-set motif] link the mol-ecules into a two-dimensional network parallel to
      the ac plane. 

PMID- 24454207
TI  - Bis{4-[(E)-2-(1H-indol-3-yl)ethen-yl]-1-methyl-pyridinium} 4-chloro-benzene
      sulfonate nitrate.
AB  - In the title mixed salt, 2C16H15N2 (+).C6H4ClO3S(-).NO3 (-), one of the cations
      shows whole mol-ecule disorder over two sets of sites in a 0.711 (7):0.289 (7)
      ratio. The 4-chorobenzenesulfon-ate anion is also disordered over two
      orientations in a 0.503 (6):0.497 (6) ratio. The cations are close to planar, the
      dihedral angles between the pyridinium and indole rings being 1.48 (3) degrees 
      in the ordered cation, and 5.62 (3) and 2.45 (3) degrees , respectively, for the
      major and minor components of the disordered cation. In the crystal, the cations
      are stacked in an anti-parallel manner approximately along the a-axis direction
      and linked with the anions via N-H?O hydrogen bonds and C-H?O inter-actions,
      generating a three-dimensional network. Weak C-H?pi and pi-pi inter-actions [with
      centroid-centroid distances of 3.561 (2)-3.969 (7) A] are also observed. 

PMID- 24454208
TI  - 5,5'-Bis(benz-yloxy)-2,2'-[hydrazine-diylidenebis(methanylyl-idene)]diphenol.
AB  - The title azine mol-ecule, C28H24N2O4, lies about a center of inversion. The
      dihedral angle between the phenyl ring and the hy-droxy-substituted ring is 70.3
      (5) degrees . The phenolic O-H group forms an intra-molecular hydrogen bond to
      the azine N atom. 

PMID- 24454209
TI  - exo-1,7-Dimethyl-4-phenyl-10-oxa-4-aza-tri-cyclo-[5.2.1.0(2,6)]dec-8-ene-3,5
      dione.
AB  - The title compound, C16H15NO3, consists of an oxabicycle fused to an N-phenyl
      substituted pyrrolidine ring anti to the double bond, affording the exo isomer.
      In the oxabicycle system, the six-membered ring presents a boat conformation,
      while the heterocyclic rings show envelope conformations with the O atom
      projected out of the plane. In the crystal, adjacent mol-ecules are linked via
      weak C-H?O hydrogen bonds, forming chains propagating along the a-axis direction.
      The chains are linked by C-H?pi inter-actions, forming two-dimensional networks
      lying parallel to the ac plane. 

PMID- 24454210
TI  - Ethyl 4-anilino-2-methyl-5-oxo-1-phenyl-2,5-di-hydro-1H-pyrrole-2-carboxyl-ate.
AB  - In the title compound, C20H20N2O3, the central 2,5-di-hydro-1H-pyrrole ring
      [r.m.s. deviation = 0.014 (1) A] is oriented at dihedral angles of 77.81 (6) and
      25.33 (6) degrees , respectively, to the attached phenyl ring and the aniline
      phenyl ring. An intra-molecular N-H?O hydrogen bond occurs. In the crystal, mol
      ecules are linked through pairs of N-H?O hydrogen bonds, forming inversion dimers
      with an R 2 (2)(10) ring motif. Two weak C-H?pi inter-actions are also observed. 

PMID- 24454211
TI  - A monoclinic polymorph of 1-benzoyl-4-thio-biuret.
AB  - The title compound, C9H9N3O2S, is a monoclinic (C2/c) polymorph of the previously
      reported triclinic structure [Kang (2013 ?). Acta Cryst. E69, o1327]. The mol
      ecule is almost planar with an r.m.s. deviation of 0.069 A from the mean plane of
      all non-H atoms. The benzoyl and terminal thio-urea fragments adopt a transoid
      conformation with respect to the central carbonyl O atom. Two intra-molecular N
      H?O hydrogen bonds are present. In the crystal, N-H?O and N-H?S inter-actions
      link the mol-ecules into zigzag chains extending along the c-axis direction. 

PMID- 24454212
TI  - Ethyl 4-(4-chloro-anilino)-1-(4-chloro-phen-yl)-2-methyl-5-oxo-2,5-di-hydro-1H
      pyrrole-2-carboxyl-ate.
AB  - In the title compound, C20H18Cl2N2O3, the dihedral angles between the central 2,5
      di-hydro-1H-pyrrole ring and the phenyl rings are 74.87 (9) and 29.09 (9) degrees
      . Intra-molecular N-H?O and C-H?O hydrogen bonds occur. In the crystal, pairs of
      N-H?O hydrogen bonds link adjacent mol-ecules into inversion dimers and form an R
      1 (2)(6)R 2 (2)(10)R 1 (2)(6) ring motif through C-H?O hydrogen bonds. 

PMID- 24454213
TI  - 5-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth-yl]-5H-dibenzo[b,f]azepine.
AB  - In the title compound, C24H20N4, the azepine ring adopts a boat conformation. The
      dihedral angle between the benzene rings fused to the azepine ring is 49.40 (9)
      degrees . The triazole ring makes a dihedral angle of 77.88 (9) degrees  with the
      terminal phenyl ring. In the crystal, mol-ecules are linked via C-H?pi inter
      actions and a parallel slipped pi-pi inter-action [centroid-centroid distance =
      3.7324 (9), normal distance = 3.4060 (6) and slippage = 1.526 A], forming a three
      dimensional network. 

PMID- 24454214
TI  - (4'-Acet-yloxy-1,3,1'-trioxo-1,3,4,4a,4b,5,6,7,9,9a-deca-hydro-spiro-[indene-2,9'
      pyrano[4,3-a]pyrrolizin]-3'-yl)methyl acetate.
AB  - In the title compound, C23H23NO8, the dihedral angle between the five- and six
      membered rings of the indene-dione moiety is 3.09 (13) degrees . The mean plane
      of the five-membered ring (which has a flat envelope conformation with the spiro
      C atom as the flap) is inclined to the mean plane of the central five-membered
      ring of the pyrrolizine unit by 76.48 (12) degrees . This central ring has a
      twist conformation on the N-C(spiro) bond. The outer ring of the pyrrolizine unit
      has an envelope conformation with the N atom as the flap. The mean planes of
      these two fused rings are inclined to one another by 65.28 (15) degrees . The
      pyran ring has a screw-boat conformation and its mean plane makes a dihedral
      angle of 29.50 (11) degrees  with the mean plane of the central five-membered
      ring of the pyrrolizine unit. In the crystal, mol-ecules are linked via C-H?O
      hydrogen bonds, forming two-dimensional networks lying parallel to the ab plane. 

PMID- 24454215
TI  - 6-Chloro-N-(pyridin-4-ylmeth-yl)pyridine-3-sulfonamide.
AB  - In the title sulfonamide derivative, C11H10ClN3O2S, the dihedral angle between
      the pyridine rings is 46.85 (12) degrees . The N atom of the chloro-pyridine ring
      is anti to the N-H bond. In the crystal, mol-ecules are linked through N-H?N
      hydrogen bonds into zigzag chains parallel to [001] with a C(7) graph-set motif. 

PMID- 24454216
TI  - 5-Acetyl-4-(3-hy-droxy-phen-yl)-6-methyl-1,2,3,4-tetra-hydro-pyrimidin-2-one-tris
      (hy-droxy-meth-yl)ammonium chloride (2/1).
AB  - The asymmetric unit of the title compound, 2C13H14N2O3.C3H10NO3 (+).Cl(-),
      contains two independent mol-ecules (A and B) of the title pyrimidine derivative
      and one ion-pair of tris-(hy-droxy-meth-yl)ammonium chloride. The pyrimidine ring
      in each pyrimidine derivative has a half-chair conformation. Its mean plane is
      inclined to the benzene ring by 87.2 (3) degrees  in mol-ecule A and 85.7 (2)
      degrees  in mol-ecule B. In the crystal, the pyrimidine derivatives are connected
      to each other by N-H?O hydrogen bonds, forming chains propagating along the b
      axis direction. The chains are linked via O-H-Cl hydrogen bonds, forming
      corrugated sheets lying parallel to the bc plane. The sheets are linked via C-H?O
      hydrogen bonds, forming a three-dimensional framework. The tris-(hy-droxy-meth
      yl)ammonium chloride mol-ecules are located in the cages of the framework. There
      are also further C-H?O hydrogen bonds and C-H?pi inter-actions present in the
      three-dimensional framework structure. Both the cation and chloride anion of the
      tris-(hy-droxy-meth-yl)ammonium chloride ion pair are disordered over two
      positions, with a refined occupancy ratio of 0.418 (8):0.582 (8) for the cation
      and 0.71 (4):0.29 (4) for the anion. 

PMID- 24454217
TI  - Ethyl 2-[1-(3-methyl-but-yl)-4-phenyl-1H-1,2,3-triazol-5-yl]-2-oxo-acetate.
AB  - In the title compound, C17H21N3O3, the non-planar (r.m.s. deviation = 0.212 A)
      ethyl (oxo)acetate group is oriented towards the phenyl substituent. The triazole
      and benzene rings are twisted with respect to each other, making a dihedral angle
      of 41.69 (6) degrees . In the crystal, mol-ecules are arranged into
      centrosymmetric R 2 (2)(10) dimers via pairs of C-H?O inter-actions involving the
      ethyl (oxo)acetate groups. In addition, the triazole rings show pi-pi stacking
      inter-actions, with their centroids at a distance of 3.745 (2) A. 

PMID- 24454218
TI  - N'-Benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide.
AB  - In the title compound, C24H20N4O2, the pyrazole ring makes dihedral angles of
      47.57 (10) degrees  and 30.56 (11) degrees  with its N-bound and C-bound phenyl
      groups, respectively. The C-N-N-C group that links the two carbonyls has a
      torsion angle of 81.5 (2) degrees . The torsion angles between the carbonyl
      groups and their adjacent pyrazole and phenyl rings are 125.89 (19) and 164.22
      (17) degrees , respectively. In the crystal, pairs of mol-ecules are linked by N
      H?O hydrogen bonds into R 2 (2)(10) ring motifs, which in turn link to form
      chains that propagate parallel to the c-axis direction. 

PMID- 24454219
TI  - (3aR,8bR)-3a,8b-Dihy-droxy-2-methyl-sulfanyl-3-nitro-1-phenyl-1,8b-di-hydro
      indeno[1,2-b]pyrrol-4(3aH)-one.
AB  - In the title compound, C18H14N2O5, the pyrrolidine ring adopts a shallow envelope
      conformation, with the C atom bearing the OH group (and remote from the N atom)
      displaced by 0.257 (2) A from the other atoms. The cyclo-pentane ring has a
      twisted conformation about the C-C bond bearing one =O and one -OH grouping. The
      dihedral angle between the five-membered rings (all atoms) is 65.54 (9) degrees 
      and the OH groups lie to the same side of the ring-junction. The mol-ecular
      structure features a weak intra-molecular O-H?O bond and a possible C-H?pi inter
      action. In the crystal, the mol-ecules are linked into [010] chains by O-H?O
      hydrogen bonds. Weak C-H?O bonds connect the chains into (100) sheets. 

PMID- 24454220
TI  - 2-N-Benzyl-2,6-dide-oxy-2,6-imino-3,4-O-iso-propyl-idene-d-allono-nitrile.
AB  - X-ray crystallography firmly established the relative stereochemistry of the
      title compound, C16H20N2O3. The acetonide ring adopts an envelope conformation
      with one of the O atoms as the flap and the piperidine ring adopts a slightly
      twisted boat conformation. The absolute configuration was determined by use of d
      ribose as the starting material. The compound exists as O-H?O hydrogen-bonded
      chains of mol-ecules running parallel to the b axis. 

PMID- 24454221
TI  - (E)-2-[2-(4-Carb-oxy-phen-yl)ethen-yl]-8-hydroxy-quinolin-1-ium chloride ethanol
      monosolvate.
AB  - In the title compound, C18H14NO3 (+).Cl(-).CH3CH2OH, the dihedral angle formed by
      the mean planes of the quinolinium and benzene rings is 3.4 (1) degrees , while
      the carb-oxy substituent is tilted at an angle of 4.8 (1) degrees  with respect
      to the benzene ring. There is a short N-H?O contact in the cation. In the
      crystal, due to the planar mol-ecular geometry, two-dimensional aggregates are
      formed parallel to (221) via C-H?O, C-H?Cl, O-H?Cl and N-H?Cl hydrogen bonds.
      Inter-layer association is accomplished by O-Hethanol?Cl and O-H?Oethanol
      hydrogen bonds and pi-pi stacking inter-actions [centroid-centroid distances vary
      from 3.6477 (12) to 3.8381 (11) A]. A supra-molecular three-dimensional
      architecture results from a stacked arrangement of layers comprising the ionic
      and hydrogen-bonded components. 

PMID- 24454222
TI  - N'-[(E)-5-Bromo-2-hy-droxy-3-meth-oxy-benzyl-idene]benzohydrazide monohydrate.
AB  - The title compound, C15H13BrN2O3.H2O, exists in an E conformation with respect to
      the azo-methane C=N double bond. The benzene and phenyl rings form dihedral
      angles of 0.46 (2) and 4.90 (3) degrees , respectively with the central C(=O)N2C
      unit. An intra-molecular O-H?N hydrogen bond occurs. In the crystal, some
      hydrazide mol-ecules are replaced by mol-ecules of the 6-bromo isomer. The Br
      atom from this admixture was refined to give a partial occupancy of 0.0443 (19).
      A supra-molecular network is built in the lattice by means of inter-molecular N
      H?O and two O-H?O inter-actions together with non-classical C-H?O inter-actions
      involving the lattice water mol-ecule stacking the mol-ecules along the b-axis
      direction. 

PMID- 24454223
TI  - (1S,3R,8R,10R)-2,2-Di-bromo-3,7,7,10-tetra-methyl-tri-cyclo-[6.4.0.0(1,3)]dodecan
      9-one.
AB  - The title compound, C16H24Br2O was synthesized by three steps from beta
      himachalene (3,5,5,9-tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo
      heptene), which was isolated from essential oil of the Atlas cedar (Cedrus
      atlantica). The mol-ecule is built up from a seven-membered ring to which a six-
      and a three-membered ring are fused. The six-membered ring shows a chair
      conformation. One C atom in the seven-membered ring and two methyl groups
      attached to the ring are disordered over two sets of sites, with an occupancy
      ratio of 0.658 (7):0.342 (7). 

PMID- 24454224
TI  - Methyl 2-amino-4,5-di-meth-oxy-benzoate.
AB  - The title compound, C10H13NO4, is essentially planar, with an r.m.s. deviation of
      0.049 A. An intra-molecular C-H?O hydrogen bond occurs and the amino group forms
      an intra-molecular N-H?Oester hydrogen bond; the other H atom forms an inter
      molecular N-H?Ocarbon-yl hydrogen bond, leading to the formation of a helical
      chain that runs along the b-axis direction. 

PMID- 24454225
TI  - (E)-1-[2-(4-Fluoro-2-nitro-styr-yl)-1-phenyl-sulfonyl-1H-indol-3-yl]propan-1-one.
AB  - In the title compound, C25H19FN2O5S, the substituted phenyl ring makes a dihedral
      angle of 12.26 (9) degrees  with the indole ring system. The nitro group is
      twisted at an angle of 26.92 (8) degrees  out of the plane of the ring to which
      it is attached. The mol-ecular structure is stabilized by weak C-H?O hydrogen
      bonds. In the crystal, weak C-H?O, C-H?F and pi-pi [centroid-centroid distance =
      3.6645 (11) A] inter-actions link the mol-ecules, forming a three-dimensional
      network. 

PMID- 24454226
TI  - (Z)-3-(1-Chloro-prop-1-en-yl)-2-methyl-1-phenyl-sulfonyl-1H-indole.
AB  - In the title compound, C18H16ClNO2S, the indole ring system forms a dihedral
      angle of 75.07 (8) degrees  with the phenyl ring. The mol-ecular structure is
      stabilized by a weak intra-molecular C-H?O hydrogen bond. In the crystal, mol
      ecules are linked by weak C-H?O hydrogen bonds, forming a chain along [10-1]. C
      H?pi inter-actions are also observed, leading to a three-dimensional network. 

PMID- 24454227
TI  - 2,9-Dimethyl-1,10-phenanthrolin-1-ium 2,4,5-tri-carb-oxy-benzoate monohydrate.
AB  - In the preparation of the title hydrated salt, C14H13N2 (+).C10H5O8 (-).H2O, a
      proton has been transfered to the 2,9-dimethyl-1,10-phenanthrolinium cation,
      forming a 2,4,5-tri-carb-oxy-benzoate anion. In the anion, the mean planes of the
      protonated carboxyl-ate groups form dihedral angles of 11.0 (5), 4.4 (5) and 80.3
      (4) degrees  with the benzene ring to which they are attached. The mean plane of
      the deprotonated carboxyl-ate group forms a dihedral angle of 10.6 (5) degrees 
      with the benzene ring. In the crystal, the anions are involved in carb-oxy-lic
      acid O-H?Ocarbox-yl hydrogen bonds, generating a two-dimensional network parallel
      to (001) containing R 4 (4)(28) and R 4 (4)(32) motifs. The 2,9-dimethyl-1,10
      phenanthrolinium cations and water mol-ecules reside between the anion layers and
      are connected to the anions via N-H?Owater and Owater-H?Ocarbox-yl hydrogen
      bonds. An intra-molecular O-H?O hydrogen bond is also observed in the anion. 

PMID- 24454228
TI  - (E)-N,N-Diethyl-2,6-diisopropyl-4-[2-(4-nitro-phen-yl)ethen-yl]aniline.
AB  - The title compound, C24H32N2O2, was prepared by Horner olefination of 4-di-ethyl
      amino-3,5-diiso-propyl-benzaldehyde and diethyl p-nitro-benzyl-phospho-nate.
      There are two independent mol-ecules (A and B) in the asymmetric unit. Their main
      axes, defined by the line connecting the N atoms of the nitro and amino groups,
      open an angle of 79.42 (3) degrees . Steric hindrance around the amino group is
      reflected in a long aryl C-N bond [1.434 (3) A for mol-ecule A and 1.440 (3) A
      for mol-ecule B], a pyramidal geometry [angle sum = 350.0 (2) degrees  for mol
      ecule A and 349.6 (2) degrees  for mol-ecule B], and dihedral angles between the
      phenyl-ene group and the plane defined by the CH2-N-CH2 unit of 86.9 (3) degrees 
      for mol-ecule A and 88.3 (3) degrees  for mol-ecule B. This gives structural
      support for the electronic decoupling of the amino group from the nearly planar
      nitro-stilbene moiety (r.m.s. deviation for C, N and O atoms = 0.097 for mol
      ecule A and 0.107 A for mol-ecule B). 

PMID- 24454229
TI  - 5-(5'-Fluoro-2'-meth-oxy-biphenyl-3-yl)-1,3,4-oxa-diazol-2-amine.
AB  - In the title compound, C15H12FN3O2, the dihedral angles between the central
      benzene ring and the pendant benzene and oxa-diazole rings are 45.05 (13) and
      15.60 (14) degrees , respectively. The C atom of the meth-oxy group is roughly
      coplanar with its attached ring [displacement = 0.178 (4) A]. In the crystal, N
      H?N hydrogen bonds link the mol-ecules into [010] chains. Weak C-H?pi inter
      actions are also observed. 

PMID- 24454230
TI  - 13-(N,N-Di-methyl-amino)-micheliolide 0.08-hydrate.
AB  - The title compound, C17H27NO3.0.08H2O {sytematic name: (3R,3aS,9R,9aS,9bS)-3-[(di
      methyl-amino)-meth-yl]-9-hy-droxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octa-hydro
      azuleno[4,5-b]furan-2(9bH)-one 0.08-hydrate}, exhibits intra-molecular O-H?O
      hydrogen bonding to form a ring of graph-set motif S(6). As well as this intra
      molecular hydrogen bond with the lactone-ring O atom, the hy-droxy H atom forms
      an O-H?O hydrogen bond to the low-occupancy partial water mol-ecule [occupancy =
      0.078 (2)]. The water mol-ecule is correlated with disorder of the N(CH3)2 group
      [major-minor occupancy factors are 0.922 (2):0.078 (2)]. The dihedral angle
      between the mean planes of the trans-fused seven-membered ring and the lactone
      ring is 4.42 (9) degrees . 

PMID- 24454231
TI  - 2-(Phenyl-selenon-yl)pyridine.
AB  - In the title compound, C11H9NO2Se, the pyridine and phenyl rings are almost
      perpendicular, with the dihedral angle between their mean planes being 79.16 (7)
      degrees . In the crystal, the mol-ecules pack so as to form ruffled sheets in the
      (110) plane connected by weak C-H?O inter-actions. In addition, there are weak pi
      pi inter-actions between the mean planes of both the phenyl [centroid-centroid
      perpendicular distance of 3.591 (2) A and slippage of 1.854 (2) A] and pyridine
      rings [centroid-centroid perpendicular distance of 3.348 (2) A and slippage of
      1.854 (2) A]. 

PMID- 24454232
TI  - 3-[1-(4-Bromo-phen-yl)eth-oxy]-2,2,5-trimethyl-4-phenyl-3-aza-hexa-ne.
AB  - The title compound, C22H30BrNO, is an alk-oxy-amine compound, an effective
      initiator in nitroxide-mediated free radical polymerization. It was prepared as a
      mixture of two diasteromers; the crystal for the X-ray analysis showed one of
      these as a pair of R,S and S,R enanti-omers. The tert-butyl and isopropyl groups
      are in an almost anti conformation in the crystal [C-N-C-C torsion angle = -168.8
      (1) degrees ], and the methyl group of the ethoxy group is in an approximate anti
      relationship to the tert-butyl group. The dihedral angle between the phenyl and
      benzene rings is 33.12 (7) degrees . The Br atom is disordered over two
      positions, with occupancies of 0.9139 (16) and 0.0861 (16). In the crystal, weak
      C-H?Br contacts link the mol-ecules into chains along [-110]. 

PMID- 24454233
TI  - Ethyl 8-(2,4-di-chloro-phen-yl)-6-methyl-1,2,4-triazolo[1,5-a]pyridine-7-carboxyl
      ate.
AB  - In the title compound, C16H13Cl2N3O2, the carboxyl-ate group and the benzene ring
      attached to the central 1,2,4-triazolo[1,5-a]pyridine bicycle are twisted from
      its mean plane by 55.6 (1) and 72.6 (1) degrees , respectively. In the crystal,
      weak C-H?O inter-actions link the mol-ecules into zigzag chains propagating in
      [100]. 

PMID- 24454234
TI  - 2-{4-Methyl-N-[(2,3,4,9-tetra-hydro-1H-carbazol-3-yl)meth-yl]benzene-sulfon
      amido}-ethyl 4-methyl-benzene-sulfonate.
AB  - In the title compound, C29H32N2O5S2, the indole ring system is nearly planar,
      with a maximum deviation of 0.013 (2) A, and the cyclo-hexenone ring has an
      envelope conformation with the methine C atom as the flap. The two methyl-benzene
      rings are approximately perpendicular to each other, making a dihedral angle of
      89.09 (8) degrees . In the crystal, N-H?O hydrogen bonds link the mol-ecules into
      a chain running along the a-axis direction, and weak C-H?O hydrogen bonds and C
      H?pi inter-actions are observed between the chains. 

PMID- 24454235
TI  - 1-Octylindoline-2,3-dione.
AB  - In the title compound, C16H21NO2, the indoline ring and the two ketone O atoms
      are approximately coplanar, the largest deviation from the mean plane being 0.063
      (2) A. The mean plane through the fused ring system is nearly perpendicular to
      the mean plane passing through the 1-octyl chain [dihedral angle = 77.53 (17)
      degrees ]. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds, forming
      a three-dimensional network. 

PMID- 24454236
TI  - 1-(2-Bromo-meth-yl-1-phenyl-sulfonyl-1H-indol-3-yl)propan-1-one.
AB  - In the title compound, C18H16BrNO3S, the dihedral angle between the phenyl ring
      and the indole ring system is 89.91 (11) degrees . The mol-ecular structure
      features weak C-H?O and C-H?Br hydrogen bonds. In the crystal, mol-ecules are
      linked by weak C-H?O hydrogen bonds, forming chains along the a-axis direction.
      The chains are further linked by C-H?pi inter-actions, forming a layer parallel
      to the ab plane. 

PMID- 24454237
TI  - 4-Formyl-2-nitro-phenyl 2-chloro-benzoate.
AB  - In the title compound, C14H8ClNO5, the benzene rings form a dihedral angle of
      19.55 (9) degrees . The mean plane of the central ester group [r.m.s. deviation =
      0.024 A] forms dihedral angles of 53.28 (13) and 36.93 (16) degrees ,
      respectively, with the nitro- and chloro-substituted rings. The nitro group forms
      a dihedral angle of 19.24 (19) degrees  with the benzene ring to which it is
      attached. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds,
      forming C(7) chains, which run along [100]. 

PMID- 24454238
TI  - 2-Amino-6-(piperidin-1-yl)-4-p-tolyl-pyridine-3,5-dicarbo-nitrile.
AB  - In the title compound, C19H19N5, the piperidine ring adopts a chair conformation.
      The pyridine ring is essentially planar, with a maximum deviation of 0.039 (2) A
      for a C atom substituted with a carbonitrile group. The mean plane of the central
      pyridine ring makes the dihedral angles of 37.90 (14) and 56.10 (12) degrees 
      with the piperidine and benzene rings, respectively. In the crystal, mol-ecules
      are linked via N-H?N and C-H?N hydrogen bonds, forming chains along [101], and
      enclosing R 2 (2)(17) ring motifs. The chains are linked by further C-H?N
      hydrogen bonds, forming two-dimensional networks lying parallel to (10-1), and
      enclosing inversion dimers with R 2 (2)(20) ring motifs. 

PMID- 24454239
TI  - 2,5-Di-meth-oxy-benzo-nitrile.
AB  - In the title mol-ecule, C9H9NO2, the non-H atoms are essentially coplanar with a
      maximum deviation of 0.027 (2) A for the C atom of one of the methyl groups. In
      the crystal, the mol-ecules are arranged into centrosymmetric pairs via pairs of
      C-H?O and C-H?N inter-actions whereas pi-pi stacking inter-actions between the
      benzene rings [centroid-centroid distance 3.91001 (15) A] organize them into
      polymeric strands propagating along the a-axis direction. There is a step of
      0.644 (2) A between the two planar parts of the centrosymmetric pair. In
      neighboring strands related by the n-glide operation, the aromatic rings are
      tilted by 29.08 (2) degrees . 

PMID- 24454240
TI  - (E)-1-(2-Hy-droxy-6-meth-oxy-phen-yl)-3-(2,4,6-tri-meth-oxy-phen-yl)prop-2-en-1
      one.
AB  - In the title mol-ecule, C19H20O6, the conformation about the C=C bond of the
      central enone group is E. The dihedral angle formed by the benzene rings is 11.6
      (2) degrees . The hy-droxy group is involved in an intra-molecular O-H?O hydrogen
      bond. In the crystal, weak C-H?O hydrogen bonds link the mol-ecules into chains
      along [010]. 

PMID- 24454241
TI  - Methyl N-(3-cyano-picolino-yl)-l-tryptophanate.
AB  - In the title compound, C19H16N4O3, the stereocenter has an l configuration; l
      tryptophan methyl ester hydro-chloride being used as a starting material. The
      indole ring system and the pyridine ring are inclined to one another by 13.55
      (14) degrees . In the crystal, adjacent mol-ecules are linked via N-H?O hydrogen
      bonds, forming chains propagating along the c-axis direction. 

PMID- 24454242
TI  - Ethyl 6-methyl-8-phenyl-1,2,4-triazolo[1,5-a]pyridine-7-carboxyl-ate.
AB  - In title compound, C16H15N3O2, the 1,2,4-triazolo[1,5-a]pyridine ring system is
      almost planar (r.m.s. deviation = 0.0068 A) and forms a dihedral angle of 61.4
      (3) degrees  with the phenyl ring. In the structure, centrosymmetrically related
      mol-ecules are linked into dimers by pairs of C-H?N hydrogen bonds. 

PMID- 24454243
TI  - 3-(Adamantan-1-yl)-1-[(4-benzyl-piperazin-1-yl)meth-yl]-4-ethyl-1H-1,2,4-triazole
      5(4H)-thione.
AB  - In the title compound, C26H37N5S, the piperazine ring adopts a chair conformation
      with the exocyclic N-C bonds in pseudo-equatorial orientations. The piperazine
      ring (all atoms) subtends dihedral angles of 79.47 (9) and 73.07 (9) degrees 
      with the triazole and benzene rings, respectively, resulting in an approximate U
      shape for the mol-ecule. No significant inter-molecular inter-actions are
      observed in the crystal. 

PMID- 24454244
TI  - N-(Adamantan-1-yl)-1,2,3,4-tetra-hydro-iso-quinoline-2-carbo-thio-amide.
AB  - In the title compound, C20H26N2S, the N-containing six-membered ring adopts a
      boat conformation and the dihedral angle between the thio-carbamide group and the
      benzene ring is 49.67 (9) degrees . An intra-molecular C-H?S hydrogen bond
      generates an S(6) ring motif. The N-H group is sterically hindered and there are
      no significant inter-molecular inter-actions beyond van der Waals contacts. 

PMID- 24454245
TI  - 6-(4-Amino-phen-yl)-2-meth-oxy-4-phenyl-nicotino-nitrile.
AB  - In the structure of the title nicotino-nitrile derivative, C19H15N3O, the
      pyridine ring makes dihedral angles of 11.50 (7) and 43.36 (8) degrees  with the
      4-amino-phenyl and phenyl rings, respectively, and the dihedral angle between the
      phenyl rings is 36.28 degrees . In the crystal, mol-ecules are linked by N-H?N
      hydrogen bonds into wave-like sheets parallel to (10-2). These sheets are stacked
      by pi-pi inter-actions between the 4-amino-phenyl rings of adjacent sheets, with
      centroid-centroid distances of 3.7499 (9) A. C-H?pi inter-actions are also
      present. 

PMID- 24454246
TI  - (11aS)-1,5,11,11a-Tetra-hydro-1-benzo-thieno[3,2-f]indolizin-3(2H)-one.
AB  - The absolute configuration of the title compound, C14H13NOS, was assigned from
      the synthesis and confirmed by the structure determination. There are two
      independent mol-ecules in the asymmetric unit. The central six-membered ring of
      the indolizine moiety adopts an envelope conformation, with the greatest
      deviations from the mean planes being 0.569 (3) and 0.561 (3) A for the
      indolizine bridgehead C atoms of the two mol-ecules. The benzothieno ring
      attached to the indolizine ring system is planar to within 0.015 (3) A in both
      mol-ecules. In the crystal, weak C-H?O and C-H?pi inter-actions lead to the
      formation of a three-dimensional framework structure. 

PMID- 24454247
TI  - 2-(6-Bromo-benzo[d]thia-zol-2-yl)-5,5-di-methyl-thia-zol-4(5H)-one.
AB  - The title compound, C12H9BrN2OS2, was obtained by reacting 6-bromo-benzo[d]thia
      zole-2-carbo-nitrile in iso-propanol with ethyl 2-mercapto-2-methyl-propano-ate
      at reflux temperature for several hours. The resulting di-methyl-oxyluciferin
      derivative shows partial double-bond character of the carbon-carbon bond between
      the two heterocyclic moieties [C-C = 1.461 (3) A]. This double bond restricts
      rotation around this C-C axis, therefore leading to an almost planar mol-ecular
      structure [N-C-C-S torsion angle = 9.7 (3) degrees ]. The five-membered
      thiazoline ring is not completely planar as a result of the bulky S atom [C-S-C-C
      torsion angle = 5.17 (12) degrees ]. 

PMID- 24454248
TI  - Benzene-1,3,5-triyl tribenzoate.
AB  - The title compound, C27H18O6, commonly known as phloroglucinol tribenzoate, is a
      standard unit for the family of benzyl ether dendrimers. The central
      phloroglucinol residue is close to planar, with out-of-plane distances for the
      three oxygen atoms of up to 0.095 (3) A, while the three attached benzoate groups
      are approximately planar. One benzoate group is twisted [C-C-O-C torsion angle =
      98.2 (3) degrees ] from the central plane, with its carbonyl O atom 2.226 (4) A
      above that plane, while the other two benzoate groups are twisted in the opposite
      direction [C-C-O-C torsion angles = 24.7 (2) and 54.8 (2) degrees ], so that
      their carbonyl O atoms are on the other side of, and closer to the central plane,
      with distances from the plane of 1.743 (4) and 1.206 (4) A. One benzoate group is
      disordered between two conformers, with occupancies of 86.9 (3) and 13.1 (3)%,
      related by a 143 (1) degrees  rotation about the bond to the central benzene
      ring. The phenyl groups of the two conformers occupy the same space. The mol
      ecule packs in the crystal with two of the three benzoate phenyl rings stacked
      parallel to symmetry-related counterparts, with perpendicular distances of 3.715
      (5) and 3.791 (5) A. The parallel rings are slipped away from each other,
      however, with centroid-centroid distances of 4.122 (2) and 4.363 (2) A,
      respectively. 

PMID- 24454249
TI  - Diethyl [4-(2,2':6',2''-terpyridine-4'-yl)phen-yl]phospho-nate.
AB  - The title compound, C25H24N3O3P, was obtained by catalytic phospho-nation of 4'
      (4-bromphen-yl)-2,2':6',2''-terpyridine. The terpyridine moiety is nearly planar,
      the dihedral angles between the central and the outer rings being 4.06 (9) and
      5.39 (9) degrees . The N atoms in the two pyridine rings are oriented nearly anti
      periplanar to that of the central ring. The benzene ring is rotated out of the
      plane of the central ring of the terpyridine unit by 34.65 (6) degrees . 

PMID- 24454250
TI  - 5-[(2-Methyl-4-nitro-1H-imidazol-1-yl)meth-yl]-1,3,4-thia-diazol-2-amine.
AB  - In the title compound, C7H8N6O2S, the dihedral angle between the imidazole and
      thia-diazole rings is 70.86 (15) degrees . In the crystal, mol-ecules are linked
      into [10-1] chains by N-H?N hydrogen bonds, which incorporate centrosymmetric R 2
      (2)(8) and R 2 (2)(18) loops. The chains are linked by C-H?O and C-H?N inter
      actions, generating a three-dimensional network. Very weak pi-pi stacking
      [centroid-centroid distance = 3.901 (17) A] is also observed. 

PMID- 24454251
TI  - 5-[(tert-Butyl-diphenyl-sil-yloxy)meth-yl]pyridazin-3(2H)-one.
AB  - In the title compound, C21H24N2O2Si, a new pyridazin-3(2H)-one derivative, the
      carbonyl group of the heterocyclic ring and the O atom of the silyl ether are
      located on the same side of the pyridazinone ring and the C-C-O-Si torsion angle
      is -140.69 (17) degrees . In the crystal, mol-ecules are linked by pairs of
      strong N-H?O hydrogen bonds into centrosymmetric dimers with graph-set notation R
      2 (2)(8). Weak C-H?pi inter-actions are also observed. 

PMID- 24454252
TI  - N'-[(E)-2-Fluoro-benzyl-idene]benzo-hydrazide.
AB  - The asymmetric unit of the title compound, C14H11FN2O, contains two independent
      mol-ecules, both of which adopt the E conformation with respect to the azomethine
      C=N bond. The mol-ecules are non-planar, with dihedral angles of 26.92 (12) and
      11.36 (11) degrees  between the benzene and phenyl rings. In the crystal, mol
      ecules are linked through N-H?O=C and N-H?N hydrogen bonds into chains along
      [101]. C-H?O contacts link these chains into layers parallel to (001). The three
      dimensional crystal packing is stabilized by pi-pi inter-actions, the shortest
      separation between the centroids of benzene rings being 3.884 (1) A. 

PMID- 24454253
TI  - Isovaline monohydrate.
AB  - The title compound, C5H11NO2.H2O, is an isomer of the alpha-amino acid valine
      that crystallizes from water in its zwitterion form as a monohydrate. It is not
      one of the 20 proteinogenic amino acids that are used in living systems and
      differs from the natural amino acids in that it has no alpha-H atom. The compound
      exhibits hydrogen bonding between the water mol-ecule and the carboxyl-ate O
      atoms and an amine H atom. In addition, there are inter-molecular hydrogen
      bonding inter-actions between the carboxyl-ate O atoms and amine H atoms. In the
      crystal, these extensive N-H?O and O-H?O hydrogen bonds lead to the formation of
      a three-dimensional network. 

PMID- 24454254
TI  - N-(4-Meth-oxy-phen-yl)-6-methyl-2-phenyl-5-{[4-(tri-fluoro-meth-yl)anilino]meth
      yl}pyrimidin-4-amine.
AB  - The title compound, C26H23F3N4O, crystallizes with two symmetry-independent mol
      ecules in the asymmetric unit, denoted A and B, which differ mainly in the
      rotation of the meth-oxy-phenyl ring. The -CF3 group of mol-ecule B is disordered
      by rotation, with the F atoms split over two sets of sites; the occupancy factor
      for the major component is 0.853 (4). The dihedral angles between the pyrimidine
      ring and the attached phenyl, meth-oxy-phenyl and tri-fluoro-methyl-phenyl rings
      are 8.1 (2), 37.5 (2) and 70.7 (2) degrees , respectively, in mol-ecule A, and
      9.3 (2), 5.3 (2) and 79.7 (2) degrees  in mol-ecule B. An intra-molecular N-H?N
      hydrogen bond occurs in each mol-ecule. In the crystal, two crystallographically
      independent mol-ecules associate into a dimer via a pair of N-H?N hydrogen bonds,
      with a resulting R 2 (2)(12) ring motif and pi-pi stacking inter-actions
      [centroid-centroid distance = 3.517 (4) A] between the pyrimidine rings. For the
      A mol-ecules, there are inter-molecular C-H?O hydrogen bonds between an aryl C
      atom of meth-oxy-phenyl ring and a meth-oxy O atom of an adjacent mol-ecule. A
      similar inter-action is lacking in the B mol-ecules. 

PMID- 24454255
TI  - 2-(3,4-Di-meth-oxy-phen-yl)-1-pentyl-4,5-diphenyl-1H-imidazole.
AB  - The central imidazole ring in the title compound, C28H30N2O2, makes dihedral
      angles of 28.42 (13), 71.22 (15) and 29.50 (14) degrees , respectively, with the
      phenyl rings in the 4- and 5-positions and the 3,4-di-meth-oxy-phenyl group. In
      the crystal, mol-ecules are linked by C-H?O and C-H?N hydrogen bonds, weak pi-pi
      stacking inter-actions [centroid-centroid distance = 3.760 (2) A] and C-H?pi
      contacts, forming a three-dimensional network. 

PMID- 24454256
TI  - (S)-(+)-cis-4'-Benzyl-oxypraziquantel.
AB  - The asymmetric unit of the title compound, C26H30N2O3 {systematic name (S)-(+)-2
      [cis-4-(benz-yloxy)cyclo-hexa-ne-carb-on-yl]-1,2,3,6,7,11b-hexa-hydro-4H-pyrazino
      [2,1-a]isoquin-olin-4-one}, consists of two independent mol-ecules in which the
      O= Camide group is syn to the N-C(C=Olactam) moiety, making dihedral angles of
      2.0 (8) and 3.7 (8) degrees . The conformation of the 1,4-disubstituted cyclo
      hexane ring is cis in each independent mol-ecule, with the carbonyl group
      occupying an equatorial position and the benz-yloxy group an axial position. In
      one mol-ecule, two C and one O atom of the benz-yloxy group are disordered over
      two sets of sites, with a refined occupancy ratio of 0.772 (8):0.228 (8). In the
      crystal, mol-ecules are linked by C-H?O inter-actions, forming ribbons parallel
      to the b-axis direction. 

PMID- 24454257
TI  - N-(2-Oxo-2,3,4,5,6,7-hexa-hydro-1H-azepin-3-yl)cyclo-hexa-necarboxamide.
AB  - In the title compound, C13H22N2O2, both the six-membered ring and the seven
      membered lactam ring adopt chair conformations. In the crystal, mol-ecules are
      linked by pairs of N-H?O hydrogen bonds between inversion-related lactam rings
      into centrosymmetric dimers with an R 2 (2)(8) graph-set motif. Further N-H?O
      hydrogen bonds link the molecules into [100] chains. 

PMID- 24454258
TI  - 2-[(Quinolin-8-yl-oxy)meth-yl]-1H-benzimid-a-zole monohydrate.
AB  - In the title hydrate, C17H13N3O.H2O, the dihedral angle between the quinoline and
      benzimidazole ring systems is 6.22 (7) degrees . The water mol-ecule is linked to
      the main mol-ecule by N-H?O and O-H?N hydrogen bonds. Further O-H?N hydrogen
      bonds link the organic molecules into C(6) chains running parallel to the b axis.

PMID- 24454259
TI  - Ethyl 6-(4-chloro-phen-yl)-4-(4-fluoro-phen-yl)-2-oxo-cyclo-hex-3-ene-1-carboxyl
      ate.
AB  - The asymmetric unit of the title compound, C21H18ClFO3, contains two independent
      mol-ecules. In one mol-ecule (A), the 4-chloro-phenyl, oxo-cyclo-hex-3-ene,
      carboxyl-ate, and ethyl groups were refined as disordered over two sets of sites
      with a 0.684 (5):0.316 (5) ratio. The cyclo-hexene ring in the disordered mol
      ecule is in a slightly distorted envelope conformation for the major component
      (with the C atom bound to the carboxylate group being the flap atom) and in a
      screw-boat conformation for the minor component. In the ordered mol-ecule (B),
      the cyclo-hexene ring is in a half-chair conformation. The dihedral angles
      between the mean planes of the fluoro- and chloro-substituted benzene rings are
      89.9 (7) (only the major component is considered for A) and 76.4 (7) degrees 
      (B). In the crystal, inversion dimers are observed along with weak C-H?O hydrogen
      bonds, which form chains along [100]. 

PMID- 24454260
TI  - 4-Chloro-phenyl quinoline-2-carboxyl-ate.
AB  - In the title compound, C16H10ClNO2, the dihedral angle between the quinoline ring
      system and the benzene ring is 14.7 (5) degrees . The carboxyl-ate group is
      twisted from the mean planes of the quinoline ring system and the benzene ring by
      17.7 (5) and 32.1 (4) degrees , respectively. In the crystal, inversion dimers
      are formed with the molecules linked by pairs of weak C-H?O inter-actions arising
      from an activated aromatic C atom adjacent to the C-Cl bond, generating R 2
      (2)(14) loops. 

PMID- 24454261
TI  - 4-Chloro-3-methyl-phenyl quinoline-2-carboxyl-ate.
AB  - In the title compound, C17H12ClNO2, the dihedral angle between the mean planes of
      the quinoline ring system and the benzene ring is 68.7 (7) degrees . The mean
      plane of the carboxyl-ate group is twisted from the latter planes by 14.0 (1) and
      80.2 (4) degrees , respectively. In the crystal, weak C-H?O inter-actions are
      observed, forming chains along [001]. In addition, pi-pi stacking inter-actions
      [centroid-centroid distances = 3.8343 (13) and 3.7372 (13)A] occur. No classical
      hydrogen bonds were observed. 

PMID- 24454262
TI  - Dimethyl (2Z)-2-[4-((1Z)-1-{2-[(2Z,5Z)-5-(2-meth-oxy-2-oxo-ethyl-idene)-4-oxo-3
      phenyl-1,3-thia-zolidin-2-yl-idene]hydra-zin-1-yl-idene}eth-yl)anilino]but-2-ene
      dio-ate.
AB  - The mol-ecule of the title compound, C26H24N4O7S, adopts a trans conformation
      about the central N-N bond, presumably to minimize steric between the
      substituents on these two atoms. An intra-molecular N-H?O hydrogen bond occurs.
      The phenyl ring is disordered over two sets of sites, with an occupancy ratio of
      0.624 (8):0.376 (8). The azolidine ring is essentially planar [maximum deviation
      = 0.008 (5) A] and makes a dihedral angle of 4.3 (2) degrees  with the benzene
      ring and dihedral angles of 74.1 (3) and 69.1 (5) degrees , respectively, with
      the mean planes of the major and minor components of the disordered phenyl ring.
      The packing in the crystal is aided by the formation of several weak C-H?O and C
      H?N inter-actions. 

PMID- 24454263
TI  - 1-(4-Methyl-phenyl-sulfon-yl)-2-{[3-methyl-4-(2,2,2-tri-fluoro-eth-oxy)pyridin-2
      yl]methyl-sulfan-yl}-1H-1,3-benzimidazole.
AB  - In the title compound, C23H20F3N3O3S2, the benzo-imidazole unit makes dihedral
      angles of 5.02 (1) and 76.42 (1) degrees , respectively, with the pyridine and
      methyl-benzene rings; the dihedral angle between the pyridine and methyl-benzene
      rings is 72.19 (1) degrees . In the crystal, mol-ecules are connected by weak C
      H?F, C-H?O and C-H?N hydrogen bonds. Weak C-H?pi inter-actions and pi-pi stacking
      [centroid-centroid distance = 3.6485 (14) A] are also observed. The overall
      packing shows a three-dimensional architecture. The crystal structure contains a
      void of 51 A(3), but no solvent mol-ecule (hexane or ethyl acetate) is located
      within it. 

PMID- 24454264
TI  - N-(1-Allyl-1H-indazol-5-yl)-4-methyl-benzene-sulfonamide.
AB  - The asymmetric unit of the title compound, C17H17N3O2S, contains two independent
      mol-ecules linked by an N-H?O hydrogen bond. The mol-ecules show different
      conformations. In the first mol-ecule, the fused five- and six-membered ring
      system is almost perpendicular to the plane through the atoms forming the allyl
      group, as indicated by the dihedral angle of 85.1 (4) degrees . The dihedral
      angle with the methyl-benzene-sulfonamide group is 78.8 (1) degrees . On the
      other hand, in the second mol-ecule, the dihedral angles between the indazole
      plane and the allyl and methyl-benzene-sulfonamide groups are 80.3 (3) and 41.5
      (1) degrees , respectively. In the crystal, mol-ecules are further linked by N
      H?N and C-H?O hydrogen bonds, forming a three-dimensional network. 

PMID- 24454265
TI  - 2-[(E)-2-(4-Meth-oxy-phen-yl)ethen-yl]-1-methyl-pyridinium iodide.
AB  - In the title mol-ecular salt, C16H10NO(+).I(-), the dihedral angle between the
      pyridinium and benzene rings is 6.61 (8) degrees . In the crystal, the cation is
      linked to the anion by a C-H?I inter-action arising from the activated aromatic C
      atom adjacent to the N(+) cation. 

PMID- 24454266
TI  - (3aR,8bR)-3a,8b-Dihy-droxy-1-(4-meth-oxy-phen-yl)-2-methyl-sulfan-yl-3-nitro-1,8b
      di-hydro-indeno-[1,2-b]pyrrol-4(3aH)-one.
AB  - In the title compound, C19H16N2O6S, the pyrrolidine ring adopts a twisted
      conformation with puckering parameters q 2 = 0.088 (3) A and Phi2 = 61.5 (14)
      degrees . The cyclo-pentane ring adopts a twisted conformation with puckering
      parameters q 2 = 0.099 (2) A and Phi2 = 242.8 (14) degrees . A weak intra
      molecular O-H?O inter-action occurs. In the crystal, pairs of C-H?O inter-actions
      generate dimers with graph-set motif R 2 (2)(24) and they are interconnected by
      pairs of O-H?O hydrogen bonds, which link the mol-ecules into inversion dimers
      with graph-set motif R 2 (2)(10). 

PMID- 24454267
TI  - 2-[(E)-2-(4-Hy-droxy-3-meth-oxy-phen-yl)ethen-yl]-1-methylpyridinium 4-bromo
      benzene-sulfonate monohydrate.
AB  - The title salt crystallized as the monohydrate C15H16NO2 (+).C6H4BrSO3 (-).H2O.
      The cation exists in an E conformation with respect to the ethynyl bond and is
      essentially planar, with a dihedral angle of 6.52 (14) degrees  between the
      pyridinium and the benzene rings. The hy-droxy and meth-oxy substituents are
      coplanar with the benzene ring to which they are attached, with an r.m.s.
      deviation of 0.0116 (3) A for the nine non-H atoms [Cmeth-yl-O-C-C torsion angle
      = -0.8 (4) degrees ]. In the crystal, the cations and anions are stacked by pi-pi
      inter-actions, with centroid-centroid distances of 3.7818 (19) and 3.9004 (17) A.
      The cations, anions and water mol-ecules are linked by O-H?O hydrogen bonds and
      weak C-H?O inter-actions, forming a three-dimensional network. 

PMID- 24454268
TI  - 3,4-Di-methyl-phenyl quinoline-2-carboxyl-ate.
AB  - In the title compound, C18H15NO2, the dihedral angle between the mean planes of
      the quinoline ring system and the phenyl ring is 48.1 (5) degrees . The mean
      plane of the carboxyl-ate group is twisted from the mean planes of the latter by
      19.8 (8) and 64.9 (5) degrees , respectively. The crystal packing features weak C
      H?O inter-actions, which form chains along [010]. 

PMID- 24454269
TI  - 2,2'-[(1,3,4-Thia-diazole-2,5-di-yl)bis-(sulfanedi-yl)]diaceto-nitrile.
AB  - In the title compound, C6H4N4S3, the 1,3,4-thia-diazole ring is essentially
      planar, with an r.m.s. deviation of 0.001 A. The two N-C-S-C torsion angles in
      the mol-ecule are -23.41 (15) and 0.62 (14) degrees . One aceto-nitrile group is
      above the plane of the 1,3,4-thia-diazole ring and the other is below it,
      indicating syn and anti orientations. In the crystal, C-H?N hydrogen bonds link
      the molecules into ribbons along [010]. 

PMID- 24454270
TI  - 2-Methyl-aspartic acid monohydrate.
AB  - The title compound, C5H9NO4.H2O, is an isomer of the alpha-amino acid glutamic
      acid that crystallizes from water in its zwitterionic form as a monohydrate. It
      is not one of the 20 proteinogenic alpha-amino acids that are used in living
      systems and differs from the natural amino acids in that it has an alpha-methyl
      group rather than an alpha-H atom. In the crystal, an O-H?O hydrogen bond is
      present between the acid and water mol-ecules while extensive N-H?O and O-H?O
      hydrogen bonds link the components into a three-dimensional array. 

PMID- 24454271
TI  - (S)-4,5-Diphenyl-1-[1-phenyl-3-(phenyl-sulfan-yl)propan-2-yl]-2-(thio-phen-2-yl)
      1H-imidazole.
AB  - In the title compound, C34H28N2S2, the central imidazole ring (r.m.s. deviation =
      0.0015 A) forms dihedral angles of 55.7 (3), 17.94 (11) and 86.27 (11) degrees ,
      respectively, with the mean planes of the attached thienyl and two phenyl
      substituents. The thienyl ring shows ring-flip disorder [occupancy ratio = 0.647
      (2):0.353 (2)]. The chiral centre maintains the S configuration of the l-phenyl
      alaninol starting material. Intra- and inter-molecular C-H?S hydrogen bonds
      involving the disordered thienyl ring are observed. 

PMID- 24454272
TI  - 4-Hy-droxy-3-meth-oxy-benzaldehyde thio-semicarbazone.
AB  - In the title compound, C9H11N3S, there is an intra-molecular O-H?O hydrogen bond
      involving the OH group and the adjacent methoxy O atom. The mol-ecule is
      essentially planar, with the maximum deviation from the mean plane of the non-H
      atoms being 0.1127 (14) A for the methyl C atom. In the crystal, mol-ecules are
      connected via centrosymmetric pairs of N-H?S and O-H?O hydrogen bonds into a two
      dimensional network parallel to (10-3). 

PMID- 24454274
TI  - Population dynamics and tuberculosis: a cross sectional study of an overlooked
      disease in Saudi Arabia.
AB  - BACKGROUND: International travel, migration and human population movements
      facilitate the spread of tuberculosis (TB). OBJECTIVE: To study the impact of
      poorly screened expatriates working in Saudi Arabia on the local incidence of
      TBs. PATIENTS AND METHODS: This cross sectional study was carried out in the
      Chest Disease Hospital, Taif. All confirmed cases of TB from June 2009 to May
      2010 admitted to the hospital were enrolled. Inclusion criteria were diagnosed
      cases of TB (pulmonary & extra-pulmonary) in patients between the ages of 14 to
      65 years. Patients with HIV and coexistent malignancies were excluded. The age,
      gender and ethnic group of each patient was recorded, and patients were divided
      into two groups. Of the two groups, Group A consisted of Taif residents and group
      B of patients referred from other cities in the country. RESULTS: Of the 686
      cases studied, 370 (54%) were Saudi nationals (Group A = 80 & Group B = 290) and
      316 (46%) cases were from other countries. Males outnumbered females and most of
      the patients were aged 20 to 29 years. The number of cases from the areas close
      to the pilgrimage sites, i.e. Makah (233) and Jeddah (275), outnumbered those in
      Taif (110). CONCLUSIONS: Our study identifies an increased prevalence of TB cases
      in areas close to the pilgrimage (Group B). The higher proportion of non-Saudi TB
      patients in group B is most likely explained by the higher number of poorly
      screened illegal expatriates in the region.

PMID- 24454276
TI  - Investigation of the effects of a high fish diet on inflammatory cytokines, blood
      pressure, and lipids in healthy older Australians.
AB  - BACKGROUND: Aging is a condition of chronic inflammation. In healthy Australians
      >=64 years, the primary aim was to determine whether four servings/week of mixed
      fish (FISH) improves serum cytokines (i.e. C-reactive protein (CRP), IL-1, IL-6,
      TNF-alpha) compared to a diet low in fish (<1 serving/week, CONTROL); the
      secondary aims were to assess the effect of the diet on blood pressure and serum
      lipids (TC, HDL-C, TG, calculated LDL-C). METHODS: An 8-week randomized, parallel
      study, stratified by CRP (<3 mg/L vs. >=3 mg/L) on entry to the study. Compliance
      was measured using 3-day weighed food records in weeks 1 and 7 of the study. A 12
      h fasting blood sample was taken at baseline and 8-weeks for erythrocyte fatty
      acids as confirmation of compliance, and measurement of serum cytokines and
      lipids. Blood pressure was measured at both time points. RESULTS: EIGHTY
      PARTICIPANTS COMPLETED THE STUDY (MEAN (SD) AGE: 69.6 (5.8) years). During week 1
      of the study, mean +/- SEM daily dietary intake of very long chain omega-3
      polyunsaturated fatty acids (VLCN n-3 PUFA) in FISH vs. CONTROL was 1,676+/-129
      mg vs. 27+/-5 mg (p<0.001). Mean (SD) gram intake of study fish and meat was 121
      (45) g and 123 (78) g, for those allocated to FISH and CONTROL, respectively.
      Mean +/- SEM percentage VLCN n-3 PUFA in erythrocytes at 8-weeks was higher in
      those allocated to FISH vs. CONTROL (10.2+/-0.2% vs. 8.2+/-0.3%, p<0.001). There
      was no between-group difference in CRP (n=80), IL-1beta (n=33) or IL-6 (n=21)
      concentrations, blood pressure, or lipids, at 8-weeks. CONCLUSIONS: Eight weeks
      consumption of four servings/week fish did not affect serum cytokine
      concentrations, blood pressure or lipids compared to a diet low in fish. In
      healthy older adults with low inflammatory burden, our results do not support
      that short-term consumption of mixed fish has a beneficial effect on selected
      cardiovascular biomarkers.

PMID- 24454275
TI  - Physicians' influence on breast cancer patient compliance.
AB  - In recent years there have been major advances in the treatment of breast cancer.
      However, taking the prescribed medication for a sufficient period of time is
      crucial to the success of any therapy. Thus far, no database-based studies have
      been published in German-speaking countries empirically examining the influence
      of the physician on the compliance of patients. The aim of this study is to
      investigate, quantify, and critically discuss the effect treating physicians have
      on the compliance of their breast cancer patients. Patients with a confirmed
      breast cancer diagnosis who started therapy (tamoxifen or aromatase inhibitors)
      between January 2001 and December 2011 were selected from the representative IMS
      Disease Analyzer database and analyzed with regard to their compliance. Practices
      were grouped into two categories concerning the compliance of all treated
      patients. A regression model showed that a breast cancer patient who is treated
      in a practice with a trend toward poor compliance has a nearly 60% higher risk
      for treatment discontinuation than would be the case in a practice with good
      compliance. It shows how important it is to motivate physicians to strive toward
      good compliance rates. 

PMID- 24454277
TI  - Regulation of neurons in the dorsal motor nucleus of the vagus by SIRT1.
AB  - Neurons in the dorsal motor nucleus of the vagus (DMV) play a critical role in
      the regulation of autonomic functions. Previous studies indicated that central
      activation of sirtuin 1 (SIRT1) has beneficial effects on homeostasis, most
      likely via modulation of the autonomic output. Sirtuins are NAD(+)-dependent
      deacetylases and have been associated with longevity. SIRT1 is one of the best
      characterized sirtuins expressed in mammals, and may be involved in the
      regulation of metabolism. Resveratrol, a SIRT1 activator reduced hyperglycemia
      likely through activation of vagal output; however, the cellular mechanisms of
      action have not been determined. In this study, whole-cell patch-clamp
      electrophysiology on acute brainstem slices was used to test the hypothesis that
      activation of SIRT1 with resveratrol enhances neurotransmission in DMV neurons.
      Application of resveratrol increased the frequency of spontaneous excitatory
      postsynaptic currents (sEPSC). This effect was KATP channel-dependent and was
      prevented with pre-application of SIRT1 inhibitor, EX527. Resveratrol also
      increased miniature EPSC (mEPSC) frequency without change in amplitude.
      Furthermore, our data demonstrated that resveratrol regulates excitatory
      neurotransmission in a PI3 kinase-dependent manner, since wortmannin, a PI3K
      inhibitor prevented the increase of mEPSC frequency caused by resveratrol. In
      conclusion, our data demonstrate that resveratrol via SIRT1 increases excitatory
      neurotransmission to DMV neurons. These observations suggest that activation of
      SIRT1 may regulate the function of subdiaphragmatic organs through controlling
      the activity of parasympathetic DMV neurons. 

PMID- 24454278
TI  - Novel autoimmune response in a tauopathy mouse model.
AB  - Molecular diagnostic tools with non-invasive properties that allow detection of
      pathological events in Alzheimer's disease (AD) and other neurodegenerative
      tauopathies are essential for the development of therapeutics. Several diagnostic
      strategies based on the identification of biomarkers have been proposed. However,
      its specificity among neurodegenerative disorders is disputable as the
      association with pathological events remains elusive. Recently, we showed that
      Amphiphysin-1 (AMPH1) protein's abundance is reduced in the central nervous
      system (CNS) of the tauopathy mouse model JNPL3 and AD brains. AMPH1 is a
      synaptic protein that plays an important role in clathrin-mediated endocytosis
      and associates with BIN1, one of the most important risk loci for AD. Also, it
      has been associated with a rare neurological disease known as Stiff-Person
      Syndrome (SPS). Auto-antibodies against AMPH1 are used as diagnostic biomarkers
      for a paraneoplastic variant of SPS. Therefore, we set up to evaluate the
      presence and abundance of auto-AMPH1 antibodies in tau-mediated
      neurodegeneration. Immunoblots and enzyme-linked immunosorbent assays (ELISA)
      were conducted to detect the presence of auto-AMPH1 antibodies in sera from
      euthanized mice that developed neurodegeneration (JNPL3) and healthy control mice
      (NTg). Results showed increased levels of auto-AMPH1 antibodies in JNPL3 sera
      compared to NTg controls. The abundance of auto-AMPH1 antibodies correlated with
      motor impairment and AMPH1 protein level decrease in the CNS. The results suggest
      that auto-AMPH1 antibodies could serve as a biomarker for the progression of tau
      mediated neurodegeneration in JNPL3 mice. 

PMID- 24454279
TI  - NMDA receptor-dependent regulation of miRNA expression and association with
      Argonaute during LTP in vivo.
AB  - microRNAs (miRNAs) are major regulators of protein synthesis in the brain. A
      major goal is to identify changes in miRNA expression underlying protein
      synthesis-dependent forms of synaptic plasticity such as long-term potentiation
      (LTP). Previous analyses focused on changes in miRNA levels in total lysate
      samples. Here, we asked whether changes in total miRNA accurately reflect changes
      in the amount of miRNA bound to Argonaute protein within the miRNA-induced
      silencing complex (miRISC). Ago2 immunoprecipitation was used to isolate RISC
      associated miRNAs following high-frequency stimulation (HFS)-induced LTP in the
      dentate gyrus of anesthetized rats. Using locked-nucleic acid-based PCR cards for
      high-throughput screening and independent validation by quantitative TaqMan RT
      PCR, we identified differential regulation of Ago2-associated and total miRNA
      expression. The ratio of Ago2/total miRNA expression was regulated
      bidirectionally in a miRNA-specific manner and was largely dependent on N-methyl
      D-aspartate receptor (NMDA) activation during LTP induction. The present results
      identify miRNA association with Ago2 as a potential control point in activity
      dependent synaptic plasticity in the adult brain. Finally, novel computational
      analysis for targets of the Ago2-associated miRNAs identifies 21 pathways that
      are enriched and differentially targeted by the miRNAs including axon guidance,
      mTOR, MAPK, Ras, and LTP. 

PMID- 24454280
TI  - Feed-forward and feedback projections of midbrain reticular formation neurons in
      the cat.
AB  - Gaze changes involving the eyes and head are orchestrated by brainstem gaze
      centers found within the superior colliculus (SC), paramedian pontine reticular
      formation (PPRF), and medullary reticular formation (MdRF). The mesencephalic
      reticular formation (MRF) also plays a role in gaze. It receives a major input
      from the ipsilateral SC and contains cells that fire in relation to gaze changes.
      Moreover, it provides a feedback projection to the SC and feed-forward
      projections to the PPRF and MdRF. We sought to determine whether these MRF
      feedback and feed-forward projections originate from the same or different
      neuronal populations by utilizing paired fluorescent retrograde tracers in cats.
      Specifically, we tested: 1. whether MRF neurons that control eye movements form a
      single population by injecting the SC and PPRF with different tracers, and 2.
      whether MRF neurons that control head movements form a single population by
      injecting the SC and MdRF with different tracers. In neither case were double
      labeled neurons observed, indicating that feedback and feed-forward projections
      originate from separate MRF populations. In both cases, the labeled
      reticulotectal and reticuloreticular neurons were distributed bilaterally in the
      MRF. However, neurons projecting to the MdRF were generally constrained to the
      medial half of the MRF, while those projecting to the PPRF, like MRF
      reticulotectal neurons, were spread throughout the mediolateral axis. Thus, the
      medial MRF may be specialized for control of head movements, with control of eye
      movements being more widespread in this structure. 

PMID- 24454281
TI  - Pericytes: brain-immune interface modulators.
AB  - The premise that the central nervous system is immune-privileged arose from the
      fact that direct contact between immune and nervous cells is hindered by the
      blood-brain barrier. However, the blood-brain barrier also comprises the
      interface between the immune and nervous systems by secreting chemo-attractant
      molecules and by modulating immune cell entry into the brain. The majority of
      published studies on the blood-brain barrier focus on endothelial cells (ECs),
      which are a critical component, but not the only one; other cellular components
      include astroglia, microglia, and pericytes. Pericytes are poorly studied in
      comparison with astrocytes or ECs; they are mesenchymal cells that can modify
      their ultrastructure and gene expression in response to changes in the central
      nervous system microenvironment. Pericytes have a unique synergistic relationship
      with brain ECs in the regulation of capillary permeability through secretion of
      cytokines, chemokines, nitric oxide, matrix metalloproteinases, and by means of
      capillary contraction. Those pericyte manifestations are related to changes in
      blood-brain barrier permeability by an increase in endocytosis-mediated transport
      and by tight junction disruption. In addition, recent reports demonstrate that
      pericytes control the migration of leukocytes in response to inflammatory
      mediators by up-regulating the expression of adhesion molecules and releasing
      chemo-attractants; however, under physiological conditions they appear to be
      immune-suppressors. Better understanding of the immune properties of pericytes
      and their participation in the effects of brain infections, neurodegenerative
      diseases, and sleep loss will be achieved by analyzing pericyte ultrastructure,
      capillary coverage, and protein expression. That knowledge may provide a
      mechanism by which pericytes participate in the maintenance of the proper
      function of the brain-immune interface. 

PMID- 24454282
TI  - The neural encoding of self-generated and externally applied movement:
      implications for the perception of self-motion and spatial memory.
AB  - The vestibular system is vital for maintaining an accurate representation of self
      motion. As one moves (or is moved) toward a new place in the environment, signals
      from the vestibular sensors are relayed to higher-order centers. It is generally
      assumed the vestibular system provides a veridical representation of head motion
      to these centers for the perception of self-motion and spatial memory. In support
      of this idea, evidence from lesion studies suggests that vestibular inputs are
      required for the directional tuning of head direction cells in the limbic system
      as well as neurons in areas of multimodal association cortex. However, recent
      investigations in monkeys and mice challenge the notion that early vestibular
      pathways encode an absolute representation of head motion. Instead, processing at
      the first central stage is inherently multimodal. This minireview highlights
      recent progress that has been made towards understanding how the brain processes
      and interprets self-motion signals encoded by the vestibular otoliths and
      semicircular canals during everyday life. The following interrelated questions
      are considered. What information is available to the higher-order centers that
      contribute to self-motion perception? How do we distinguish between our own self
      generated movements and those of the external world? And lastly, what are the
      implications of differences in the processing of these active vs. passive
      movements for spatial memory? 

PMID- 24454283
TI  - Reorganization of the brain and heart rhythm during autogenic meditation.
AB  - The underlying changes in heart coherence that are associated with reported EEG
      changes in response to meditation have been explored. We measured EEG and heart
      rate variability (HRV) before and during autogenic meditation. Fourteen subjects
      participated in the study. Heart coherence scores were significantly increased
      during meditation compared to the baseline. We found near significant decrease in
      high beta absolute power, increase in alpha relative power and significant
      increases in lower (alpha) and higher (above beta) band coherence during 3~min
      epochs of heart coherent meditation compared to 3~min epochs of heart non
      coherence at baseline. The coherence and relative power increase in alpha band
      and absolute power decrease in high beta band could reflect relaxation state
      during the heart coherent meditation. The coherence increase in the higher (above
      beta) band could reflect cortico-cortical local integration and thereby affect
      cognitive reorganization, simultaneously with relaxation. Further research is
      still needed for a confirmation of heart coherence as a simple window for the
      meditative state. 

PMID- 24454285
TI  - Pupil dilations reflect why rembrandt biased female portraits leftward and males
      rightward.
AB  - Portrait painters are experts at examining faces and since emotional content may
      be expressed differently on each side of the face, consider that Rembrandt biased
      his male portraits to show their right-cheek more often and female portraits to
      show their left-cheek more often. This raises questions regarding the emotional
      significance of such biased positions. I presented rightward and leftward facing
      male and female portraits. I measured observers' pupil size while asking
      observers to report how (dis)pleasing they found each image. This was a
      methodological improvement over the type of research initially done by Eckhard
      Hess who claimed that pupils dilate to pleasant images and constrict to
      unpleasant images. His work was confounded since his images' luminances and
      contrasts across conditions were inconsistent potentially affecting pupil size.
      To overcome this limitation I presented rightward or leftward facing male and
      female portraits by Rembrandt to observers in either their original or mirror
      reversed position. I found that in viewing male portraits pupil diameter was a
      function of arousal. That is, larger pupil diameter occurred for images rated
      both low and high in pleasantness. This was not the case with female portraits. I
      discuss these findings in regard to the perceived dominance of males and how
      emotional expressions may be driven by hemispheric laterality. 

PMID- 24454284
TI  - Don't stand so close to me: psychopathy and the regulation of interpersonal
      distance.
AB  - Psychopathy is characterized by callous and unemotional personality traits, such
      as reduced empathy and remorse, and a tendency toward deviant interpersonal
      behaviors. It has been suggested that subtle behavioral cues in individuals with
      high levels of psychopathic traits may betray their personality during
      interpersonal interactions, but little research has addressed what these clues
      might be. In this study, we investigated whether psychopathic traits predict
      interpersonal distance preferences, which have been previously linked to amygdala
      functioning. 46 healthy participants performed a behavioral task in which the
      distance they preferred to maintain between themselves and an experimenter was
      measured across a series of trials. Psychopathic traits, including
      Coldheartedness, Fearless Dominance, and Self-centered Impulsivity were assessed
      using the Psychopathic Personality Inventory-Revised (Lilienfeld and Widows,
      2005). Results demonstrated that Coldheartedness predicted preferred
      interpersonal distance, with more coldhearted participants preferring shorter
      distances. These findings suggest that interpersonal distance preferences may
      signal psychopathic traits, particularly callousness, supporting accounts of
      amygdala dysfunction in psychopathy. 

PMID- 24454286
TI  - The Laplacian spectrum of neural networks.
AB  - The brain is a complex network of neural interactions, both at the microscopic
      and macroscopic level. Graph theory is well suited to examine the global network
      architecture of these neural networks. Many popular graph metrics, however,
      encode average properties of individual network elements. Complementing these
      "conventional" graph metrics, the eigenvalue spectrum of the normalized Laplacian
      describes a network's structure directly at a systems level, without referring to
      individual nodes or connections. In this paper, the Laplacian spectra of the
      macroscopic anatomical neuronal networks of the macaque and cat, and the
      microscopic network of the Caenorhabditis elegans were examined. Consistent with
      conventional graph metrics, analysis of the Laplacian spectra revealed an
      integrative community structure in neural brain networks. Extending previous
      findings of overlap of network attributes across species, similarity of the
      Laplacian spectra across the cat, macaque and C. elegans neural networks suggests
      a certain level of consistency in the overall architecture of the anatomical
      neural networks of these species. Our results further suggest a specific network
      class for neural networks, distinct from conceptual small-world and scale-free
      models as well as several empirical networks. 

PMID- 24454287
TI  - The epithelium in idiopathic pulmonary fibrosis: breaking the barrier.
AB  - Idiopathic pulmonary fibrosis is a progressive disease of unknown etiology
      characterized by a dysregulated wound healing response that leads to fatal
      accumulation of fibroblasts and extracellular matrix (ECM) in the lung, which
      compromises tissue architecture and lung function capacity. Injury to type II
      alveolar epithelial cells is thought to be the key event for the initiation of
      the disease, and so far both genetic factors, such as mutations in telomerase and
      MUC5B genes as well as environmental components, like cigarette smoking, exposure
      to asbestos and viral infections have been implicated as potential initiating
      triggers. The injured epithelium then enters a state of senescence-associated
      secretory phenotype whereby it produces both pro-inflammatory and pro-fibrotic
      factors that contribute to the wound healing process in the lung. Immune cells,
      like macrophages and neutrophils as well as activated myofibroblasts then
      perpetuate this cascade of epithelial cell apoptosis and proliferation by release
      of pro-fibrotic transforming growth factor beta and continuous deposition of ECM
      stiffens the basement membrane, altogether having a deleterious impact on
      epithelial cell function. In this review, we describe the role of the epithelium
      as both a physical and immunological barrier between environment and self in the
      homeostatic versus diseased lung and explore the potential mechanisms of
      epithelial cell injury and the impact of loss of epithelial cell permeability and
      function on cytokine production, inflammation, and myofibroblast activation in
      the fibrotic lung. 

PMID- 24454288
TI  - Population-based colorectal cancer screening: comparison of two fecal occult
      blood test.
AB  - BACKGROUND: The aim of screening for colorectal cancer is to improve prognosis by
      the detection of cancer at its early stages. In order to inform the decision on
      the specific test to be used in the population-based program in the Basque
      Autonomous Region (Spain), we compared two immunochemical fecal occult blood
      quantitative tests (I-FOBT). METHODS: Residents of selected study areas, aged 50
      69 years, were invited to participate in the screening. Two tests based on latex
      agglutination (OC-Sensor and FOB Gold) were randomly assigned to different study
      areas. A colonoscopy was offered to patients with a positive test result. The cut
      off point used to classify a result as positive, according to manufacturer's
      recommendations, was 100 ng/ml for both tests. RESULTS: The invited population
      included 37,999 individuals. Participation rates were 61.8% (n = 11,162) for OC
      Sensor and 59.1% (n = 11,786) for FOB Gold (p = 0.008). Positive rate for OC
      Sensor was 6.6% (n = 737) and 8.5% (n = 1,002) for FOB Gold (p < 0.0001). Error
      rates were higher for FOB gold (2.3%) than for OC-Sensor (0.2%; p < 0.0001).
      Predictive positive value (PPV) for total malignant and premalignant lesions was
      62.4% for OC-Sensor and 58.9% for FOB Gold (p = 0.137), respectively. CONCLUSION:
      OC-Sensor test appears to be superior for I-FOBT-based colorectal cancer
      screening, given its acceptance, ease of use, associated small number of errors
      and its screening accuracy. FOB Gold on the other hand, has higher rate of
      positive values, with more colonoscopies performed, it shows higher detection
      incidence rates, but involves more false positives.

PMID- 24454291
TI  - Trichinella spiralis, potential model nematode for epigenetics and its
      implication in metazoan parasitism.
AB  - The recent discovery of DNA methylation in the nematode T.spiralis may raise the
      possibility of using it as a potential model organism for epigenetic studies
      instead of C. elegans, which is deficient in this important epigenetic
      modification. In contrast to the free-living nematode C. elegans, T. spiralis is
      a parasitic worm that possesses a complicated life cycle and undergoes a complex
      developmental regulation of genes. We emphasize that the differential methylomes
      in the different life-history stages of T. spiralis can provide insight on how
      DNA methylation is triggered and regulated. In particular, we have demonstrated
      that DNA methylation is involved in the regulation of its parasitism-related
      genes. Further computational analyses indicated that the regulatory machinery for
      DNA methylation can also be found in the T. spiralis genome. By a logical
      extension of this point, we speculate that comprehensively addressing the
      epigenetic machinery of T. spiralis may help to understand epigenetics in
      invertebrates. Furthermore, considering the implication of epigenetics in
      metazoan parasitism, using T. spiralis as an epigenetic model organism may
      further contribute to drug development against metazoan parasites. 

PMID- 24454289
TI  - The growing use of herbal medicines: issues relating to adverse reactions and
      challenges in monitoring safety.
AB  - The use of herbal medicinal products and supplements has increased tremendously
      over the past three decades with not less than 80% of people worldwide relying on
      them for some part of primary healthcare. Although therapies involving these
      agents have shown promising potential with the efficacy of a good number of
      herbal products clearly established, many of them remain untested and their use
      are either poorly monitored or not even monitored at all. The consequence of this
      is an inadequate knowledge of their mode of action, potential adverse reactions,
      contraindications, and interactions with existing orthodox pharmaceuticals and
      functional foods to promote both safe and rational use of these agents. Since
      safety continues to be a major issue with the use of herbal remedies, it becomes
      imperative, therefore, that relevant regulatory authorities put in place
      appropriate measures to protect public health by ensuring that all herbal
      medicines are safe and of suitable quality. This review discusses toxicity
      related issues and major safety concerns arising from the use of herbal medicinal
      products and also highlights some important challenges associated with effective
      monitoring of their safety. 

PMID- 24454290
TI  - Connexin and pannexin (hemi)channels in the liver.
AB  - The liver was among the first organs in which connexin proteins have been
      identified. Hepatocytes harbor connexin32 and connexin26, while non-parenchymal
      liver cells typically express connexin43. Connexins give rise to hemichannels,
      which dock with counterparts on adjacent cells to form gap junctions. Both
      hemichannels and gap junctions provide pathways for communication, via paracrine
      signaling or direct intercellular coupling, respectively. Over the years,
      hepatocellular gap junctions have been shown to regulate a number of liver
      specific functions and to drive liver cell growth. In the last few years, it has
      become clear that connexin hemichannels are involved in liver cell death,
      particularly in hepatocyte apoptosis. This also holds true for hemichannels
      composed of pannexin1, a connexin-like protein recently identified in the liver.
      Moreover, pannexin1 hemichannels are key players in the regulation of hepatic
      inflammatory processes. The current paper provides a concise overview of the
      features of connexins, pannexins and their channels in the liver. 

PMID- 24454292
TI  - Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+)
      exchanger NHE5.
AB  - Neuronal precursor cells extend multiple neurites during development, one of
      which extends to form an axon whereas others develop into dendrites. Chemical
      stimulation of N-methyl D-aspartate (NMDA) receptor in fully-differentiated
      neurons induces projection of dendritic spines, small spikes protruding from
      dendrites, thereby establishing another layer of polarity within the dendrite.
      Neuron-enriched Na(+)/H(+) exchanger NHE5 contributes to both neurite growth and
      dendritic spine formation. In resting neurons and neuro-endocrine cells, neuron
      enriched NHE5 is predominantly associated with recycling endosomes where it
      colocalizes with nerve growth factor (NGF) receptor TrkA. NHE5 potently acidifies
      the lumen of TrkA-positive recycling endosomes and regulates cell-surface
      targeting of TrkA, whereas chemical stimulation of NMDA receptors rapidly
      recruits NHE5 to dendritic spines, alkalinizes dendrites and down-regulates the
      dendritic spine formation. Possible roles of NHE5 in neuronal signaling via
      proton movement in subcellular compartments are discussed. 

PMID- 24454294
TI  - The clinical relevance of neurocognitive measures in addiction.
AB  - One of the major challenges in addiction treatment is relapse prevention, as
      rates of relapse following treatment remain very high across the main classes of
      drugs of abuse. Relapse prevention could be improved by a better understanding of
      the factors that influence treatment outcomes, including better predictors of
      risk of relapse following treatment. Recent developments in cognitive
      neuroscience point to neurocognitive measures (i.e., brain-imaging measures
      during cognitive-task performance) as potential predictors of relapse. These
      might even be better predictors than self-report measures, such as craving. We
      first give an overview of the current state of the field, and then discuss the
      outstanding challenges and future directions in this area of research. 

PMID- 24454293
TI  - Mindfulness training targets neurocognitive mechanisms of addiction at the
      attention-appraisal-emotion interface.
AB  - Prominent neuroscience models suggest that addictive behavior occurs when
      environmental stressors and drug-relevant cues activate a cycle of cognitive,
      affective, and psychophysiological mechanisms, including dysregulated
      interactions between bottom-up and top-down neural processes, that compel the
      user to seek out and use drugs. Mindfulness-based interventions (MBIs) target
      pathogenic mechanisms of the risk chain linking stress and addiction. This review
      describes how MBIs may target neurocognitive mechanisms of addiction at the
      attention-appraisal-emotion interface. Empirical evidence is presented suggesting
      that MBIs ameliorate addiction by enhancing cognitive regulation of a number of
      key processes, including: clarifying cognitive appraisal and modulating negative
      emotions to reduce perseverative cognition and emotional arousal; enhancing
      metacognitive awareness to regulate drug-use action schema and decrease addiction
      attentional bias; promoting extinction learning to uncouple drug-use triggers
      from conditioned appetitive responses; reducing cue-reactivity and increasing
      cognitive control over craving; attenuating physiological stress reactivity
      through parasympathetic activation; and increasing savoring to restore natural
      reward processing. Treatment and research implications of our neurocognitive
      framework are presented. We conclude by offering a temporally sequenced
      description of neurocognitive processes targeted by MBIs through a hypothetical
      case study. Our neurocognitive framework has implications for the optimization of
      addiction treatment with MBIs. 

PMID- 24454296
TI  - IBES: a tool for creating instructions based on event segmentation.
AB  - Receiving informative, well-structured, and well-designed instructions supports
      performance and memory in assembly tasks. We describe IBES, a tool with which
      users can quickly and easily create multimedia, step-by-step instructions by
      segmenting a video of a task into segments. In a validation study we demonstrate
      that the step-by-step structure of the visual instructions created by the tool
      corresponds to the natural event boundaries, which are assessed by event
      segmentation and are known to play an important role in memory processes. In one
      part of the study, 20 participants created instructions based on videos of two
      different scenarios by using the proposed tool. In the other part of the study,
      10 and 12 participants respectively segmented videos of the same scenarios
      yielding event boundaries for coarse and fine events. We found that the visual
      steps chosen by the participants for creating the instruction manual had
      corresponding events in the event segmentation. The number of instructional steps
      was a compromise between the number of fine and coarse events. Our interpretation
      of results is that the tool picks up on natural human event perception processes
      of segmenting an ongoing activity into events and enables the convenient transfer
      into meaningful multimedia instructions for assembly tasks. We discuss the
      practical application of IBES, for example, creating manuals for differing
      expertise levels, and give suggestions for research on user-oriented
      instructional design based on this tool. 

PMID- 24454295
TI  - Brain signal variability as a window into the bidirectionality between music and
      language processing: moving from a linear to a nonlinear model.
AB  - There is convincing empirical evidence for bidirectional transfer between music
      and language, such that experience in either domain can improve mental processes
      required by the other. This music-language relationship has been studied using
      linear models (e.g., comparing mean neural activity) that conceptualize brain
      activity as a static entity. The linear approach limits how we can understand the
      brain's processing of music and language because the brain is a nonlinear system.
      Furthermore, there is evidence that the networks supporting music and language
      processing interact in a nonlinear manner. We therefore posit that the neural
      processing and transfer between the domains of language and music are best viewed
      through the lens of a nonlinear framework. Nonlinear analysis of
      neurophysiological activity may yield new insight into the commonalities,
      differences, and bidirectionality between these two cognitive domains not
      measurable in the local output of a cortical patch. We thus propose a novel
      application of brain signal variability (BSV) analysis, based on mutual
      information and signal entropy, to better understand the bidirectionality of
      music-to-language transfer in the context of a nonlinear framework. This approach
      will extend current methods by offering a nuanced, network-level understanding of
      the brain complexity involved in music-language transfer. 

PMID- 24454297
TI  - Low level perceptual, not attentional, processes modulate distractor interference
      in high perceptual load displays: evidence from neglect/extinction.
AB  - According to perceptual load theory (Lavie, 2005) distractor interference is
      determined by the availability of attentional resources. If target processing
      does not exhaust resources (with low perceptual load) distractor processing will
      take place resulting in interference with a primary task; however, when target
      processing uses-up attentional capacity (with high perceptual load) interference
      can be avoided. An alternative account (Tsal and Benoni, 2010a) suggests that
      perceptual load effects can be based on distractor dilution by the mere presence
      of additional neutral items in high-load displays so that the effect is not
      driven by the amount of attention resources required for target processing. Here
      we tested whether patients with unilateral neglect or extinction would show
      dilution effects from neutral items in their contralesional
      (neglected/extinguished) field, even though these items do not impose increased
      perceptual load on the target and at the same time attract reduced attentional
      resources compared to stimuli in the ipsilesional field. Thus, such items do not
      affect the amount of attention resources available for distractor processing. We
      found that contralesional neutral elements can eliminate distractor interference
      as strongly as centrally presented ones in neglect/extinction patients, despite
      contralesional items being less well attended. The data are consistent with an
      account in terms of perceptual dilution of distracters rather than available
      resources for distractor processing. We conclude that distractor dilution can
      underlie the elimination of distractor interference in visual displays. 

PMID- 24454298
TI  - Motor control strategies and the effects of fatigue on golf putting performance.
AB  - This study investigated the strategies used by elite golfers to scale their
      putting actions to achieve putts of different distances. There were three aims;
      to determine if putting actions are scaled by manipulating swing amplitude as
      predicted by Craig etal. (2000), to establish the test-retest reliability of the
      Craig et al. model, and to evaluate whether elite golfers changed their putting
      scaling strategies when fatigued. Putting actions were recorded at baseline (time
      1) and 6 months later (time 2) and after walking at 70% of maximum heart rate for
      1 h (time 3). Participants performed a total of 80 putts which varied in distance
      (1 m, 2 m, 3 m, and 4 m) at time 1 and time 2, and 100 putts to the same
      distances when they were fatigued (time 3). Multiple regression was used to
      examine how the golfers systematically changed the movement control variables in
      the Craig etal. (2000) model to achieve golf putts of different distances.
      Although swing amplitude was a strong predictor of putterhead velocity at ball
      impact for all of the participants at baseline (time 1), each golfer
      systematically changed aspects of the timing of their action. A comparison of the
      regression models between time 1 and time 2 showed no significant changes in the
      scaling strategies used, indicating that the Craig etal. (2000) model had good
      test-retest reliability. Fatigue was associated with a decrease in the number of
      putts that were successfully holed and significant changes in the scaling
      strategies used by three of the golfers, along with a trend for increasing the
      putterhead velocity at ball impact. These motor control changes in performance
      when fatigued were evident in successful putts indicating that even when these
      elite golfers were able to achieve the goal of holing the putt, moderate levels
      of fatigue were influencing the consistency of their performance. Theoretical
      implications for the Craig etal. (2000) model and practical implications for
      elite golfers are discussed. 

PMID- 24454299
TI  - Action-based effects on music perception.
AB  - The classical, disembodied approach to music cognition conceptualizes action and
      perception as separate, peripheral processes. In contrast, embodied accounts of
      music cognition emphasize the central role of the close coupling of action and
      perception. It is a commonly established fact that perception spurs action
      tendencies. We present a theoretical framework that captures the ways in which
      the human motor system and its actions can reciprocally influence the perception
      of music. The cornerstone of this framework is the common coding theory,
      postulating a representational overlap in the brain between the planning, the
      execution, and the perception of movement. The integration of action and
      perception in so-called internal models is explained as a result of associative
      learning processes. Characteristic of internal models is that they allow intended
      or perceived sensory states to be transferred into corresponding motor commands
      (inverse modeling), and vice versa, to predict the sensory outcomes of planned
      actions (forward modeling). Embodied accounts typically refer to inverse modeling
      to explain action effects on music perception (Leman, 2007). We extend this
      account by pinpointing forward modeling as an alternative mechanism by which
      action can modulate perception. We provide an extensive overview of recent
      empirical evidence in support of this idea. Additionally, we demonstrate that
      motor dysfunctions can cause perceptual disabilities, supporting the main idea of
      the paper that the human motor system plays a functional role in auditory
      perception. The finding that music perception is shaped by the human motor system
      and its actions suggests that the musical mind is highly embodied. However, we
      advocate for a more radical approach to embodied (music) cognition in the sense
      that it needs to be considered as a dynamical process, in which aspects of
      action, perception, introspection, and social interaction are of crucial
      importance. 

PMID- 24454301
TI  - Change my body, change my mind: the effects of illusory ownership of an outgroup
      hand on implicit attitudes toward that outgroup.
AB  - The effect of multisensory-induced changes on body-ownership and self-awareness
      using bodily illusions has been well established. More recently, experimental
      manipulation of bodily illusions have been combined with social cognition tasks
      to investigate whether changes in body-ownership can in turn change the way we
      perceive others. For example, experiencing ownership over a dark-skin rubber hand
      reduces implicit bias against dark-skin groups. Several studies have also shown
      that processing of skin color and facial features play an important role in
      judgements of racial typicality and racial categorization independently and in an
      additive manner. The present study aimed at examining whether using multisensory
      stimulation to induce feelings of body-ownership over a dark-skin rubber hand
      would lead to an increase in positive attitudes toward black faces. We here show,
      that the induced ownership of a body-part of a different skin color affected the
      participants' implicit attitudes when processing facial features, in addition to
      the processing of skin color shown previously. Furthermore, when the levels of
      pre-existing attitudes toward black people were taken into account, the effect of
      the rubber hand illusion on the post-stimulation implicit attitudes was only
      significant for those participants who had a negative initial attitude toward
      black people, with no significant effects found for those who had positive
      initial attitudes toward black people. Taken together, our findings corroborate
      the hypothesis that the representation of the self and its relation to others, as
      given to us by body-related multisensory processing, is critical in maintaining
      but also in changing social attitudes. 

PMID- 24454302
TI  - Cognitive strategies to regulate emotions-current evidence and future directions.

PMID- 24454300
TI  - The olfactory system as the gateway to the neural correlates of consciousness.
AB  - How consciousness is generated by the nervous system remains one of the greatest
      mysteries in science. Investigators from diverse fields have begun to unravel
      this puzzle by contrasting conscious and unconscious processes. In this way, it
      has been revealed that the two kinds of processes differ in terms of the
      underlying neural events and associated cognitive mechanisms. We propose that,
      for several reasons, the olfactory system provides a unique portal through which
      to examine this contrast. For this purpose, the olfactory system is beneficial in
      terms of its (a) neuroanatomical aspects, (b) phenomenological and
      cognitive/mechanistic properties, and (c) neurodynamic (e.g., brain oscillations)
      properties. In this review, we discuss how each of these properties and aspects
      of the olfactory system can illuminate the contrast between conscious and
      unconscious processing in the brain. We conclude by delineating the most fruitful
      avenues of research and by entertaining hypotheses that, in order for an
      olfactory content to be conscious, that content must participate in a network
      that is large-scale, both in terms of the neural systems involved and the scope
      of information integration. 

PMID- 24454303
TI  - Mindful creativity: the influence of mindfulness meditation on creative thinking.

PMID- 24454305
TI  - Effect of subthalamic stimulation on voice and speech in Parkinson's disease: for
      the better or worse?
AB  - BACKGROUND: Deep brain stimulation of the subthalamic nucleus, although highly
      effective for the treatment of motor impairment in Parkinson's disease (PD), can
      induce speech deterioration in a subgroup of patients. The aim of the current
      study was to survey (1) if there are distinctive stimulation effects on the
      different parameters of voice and speech and (2) if there is a special pattern of
      preexisting speech abnormalities indicating a risk for further worsening under
      stimulation. METHODS: N = 38 patients with PD had to perform a speech test
      without medication with stimulation ON (StimON) and stimulation OFF (StimOFF).
      Speech samples were analyzed: (1) according to a four-dimensional perceptual
      speech score and (2) by acoustic analysis to obtain quantifiable measures of
      distinctive speech parameters. RESULTS: Quality of voice was ameliorated with
      StimON, and there were trends of increased loudness and better pitch variability.
      N = 8 patients featured a deterioration of speech with StimON, caused by
      worsening of articulation or/and fluency. These patients already had more severe
      overall speech impairment with characteristic features of articulatory slurring
      and articulatory acceleration under StimOFF condition. CONCLUSION: The influence
      of subthalamic StimON Parkinsonian speech differs considerably between individual
      patients, however, there is a trend to amelioration of voice quality and prosody.
      Patients with stimulation-associated speech deterioration featured higher overall
      speech impairment and showed a distinctive pattern of articulatory abnormalities
      at baseline. Further investigations to confirm these preliminary findings are
      necessary to allow neurologists to pre-surgically estimate the individual risk of
      deterioration of speech under stimulation.

PMID- 24454304
TI  - Time dysperception perspective for acquired brain injury.
AB  - Distortions of time perception are presented by a number of neuropsychiatric
      illnesses. Here we survey timing abilities in clinical populations with focal
      lesions in key brain structures recently implicated in human studies of timing.
      We also review timing performance in amnesic and traumatic brain injured patients
      in order to identify the nature of specific timing disorders in different brain
      damaged populations. We purposely analyzed the complex relationship between both
      cognitive and contextual factors involved in time estimation, as to characterize
      the correlation between timed and other cognitive behaviors in each group. We
      assume that interval timing is a solid construct to study cognitive dysfunctions
      following brain injury, as timing performance is a sensitive metric of
      information processing, while temporal cognition has the potential of influencing
      a wide range of cognitive processes. Moreover, temporal performance is a
      sensitive assay of damage to the underlying neural substrate after a brain
      insult. Further research in neurological and psychiatric patients will clarify
      whether time distortions are a manifestation of, or a mechanism for, cognitive
      and behavioral symptoms of neuropsychiatric disorders. 

PMID- 24454306
TI  - "Tau oligomers," what we know and what we don't know.

PMID- 24454307
TI  - Opposite influence of light and blindness on pituitary-gonadal function.
AB  - Some environmental factors may influence the pituitary-gonadal function. Among
      these, light plays an important role in animals and in humans. The effect of
      light on the endocrine system is mediated by the pineal gland, through the
      modulation of melatonin secretion. In fact, melatonin secretion is stimulated by
      darkness and suppressed by light, thus its circadian rhythm peaks at night. Light
      plays a favorable action on the hypothalamic-pituitary axis likely inhibiting
      melatonin secretion, while the exogenous melatonin administration does not seem
      to impair the hormonal secretions of this axis. The basal and rhythmic pituitary
      gonadal hormone secretions are regulated by a central clock gene and some
      independent clock genes in the peripheral tissues. Light is able to induce the
      expression of some of these genes, thus playing an important role in regulating
      the hormonal secretions of pituitary-gonadal axis and the sexual and reproductive
      function in animals and humans. The lack of light stimulus in blind subjects
      induces increase in plasma melatonin concentrations with a free-running rhythm of
      secretion, which impairs the hormonal secretions of pituitary-gonadal axis,
      causing disorders of reproductive processes in both sexes. 

PMID- 24454308
TI  - Transgenic strategies to confer resistance against viruses in rice plants.
AB  - Rice (Oryza sativa L.) is cultivated in more than 100 countries and supports
      nearly half of the world's population. Developing efficient methods to control
      rice viruses is thus an urgent necessity because viruses cause serious losses in
      rice yield. Most rice viruses are transmitted by insect vectors, notably
      planthoppers and leafhoppers. Viruliferous insect vectors can disperse their
      viruses over relatively long distances, and eradication of the viruses is very
      difficult once they become widespread. Exploitation of natural genetic sources of
      resistance is one of the most effective approaches to protect crops from virus
      infection; however, only a few naturally occurring rice genes confer resistance
      against rice viruses. Many investigators are using genetic engineering of rice
      plants as a potential strategy to control viral diseases. Using viral genes to
      confer pathogen-derived resistance against crops is a well-established procedure,
      and the expression of various viral gene products has proved to be effective in
      preventing or reducing infection by various plant viruses since the 1990s. RNA
      interference (RNAi), also known as RNA silencing, is one of the most efficient
      methods to confer resistance against plant viruses on their respective crops. In
      this article, we review the recent progress, mainly conducted by our research
      group, in transgenic strategies to confer resistance against tenuiviruses and
      reoviruses in rice plants. Our findings also illustrate that not all RNAi
      constructs against viral RNAs are equally effective in preventing virus infection
      and that it is important to identify the viral "Achilles' heel" gene to target
      for RNAi attack when engineering plants. 

PMID- 24454309
TI  - Phages of non-dairy lactococci: isolation and characterization of PhiL47, a phage
      infecting the grass isolate Lactococcus lactis ssp. cremoris DPC6860.
AB  - Lactococci isolated from non-dairy sources have been found to possess enhanced
      metabolic activity when compared to dairy strains. These capabilities may be
      harnessed through the use of these strains as starter or adjunct cultures to
      produce more diverse flavor profiles in cheese and other dairy products. To
      understand the interactions between these organisms and the phages that infect
      them, a number of phages were isolated against lactococcal strains of non-dairy
      origin. One such phage, PhiL47, was isolated from a sewage sample using the grass
      isolate L. lactis ssp. cremoris DPC6860 as a host. Visualization of phage virions
      by transmission electron microscopy established that this phage belongs to the
      family Siphoviridae and possesses a long tail fiber, previously unseen in dairy
      lactococcal phages. Determination of the lytic spectrum revealed a broader than
      expected host range, with PhiL47 capable of infecting 4 industrial dairy strains,
      including ML8, HP and 310, and 3 additional non-dairy isolates. Whole genome
      sequencing of PhiL47 revealed a dsDNA genome of 128, 546 bp, making it the
      largest sequenced lactococcal phage to date. In total, 190 open reading frames
      (ORFs) were identified, and comparative analysis revealed that the predicted
      products of 117 of these ORFs shared greater than 50% amino acid identity with
      those of L. lactis phage Phi949, a phage isolated from cheese whey. Despite their
      different ecological niches, the genomic content and organization of PhiL47 and
      Phi949 are quite similar, with both containing 4 gene clusters oriented in
      different transcriptional directions. Other features that distinguish PhiL47 from
      Phi949 and other lactococcal phages, in addition to the presence of the tail
      fiber and the genome length, include a low GC content (32.5%) and a high number
      of predicted tRNA genes (8). Comparative genome analysis supports the conclusion
      that PhiL47 is a new member of the 949 lactococcal phage group which currently
      includes the dairy Phi949. 

PMID- 24454310
TI  - Allelic variation in Salmonella: an underappreciated driver of adaptation and
      virulence.
AB  - Salmonella enterica causes substantial morbidity and mortality in humans and
      animals. Infection and intestinal colonization by S. enterica require virulence
      factors that mediate bacterial binding and invasion of enterocytes and innate
      immune cells. Some S. enterica colonization factors and their alleles are host
      restricted, suggesting a potential role in regulation of host specificity. Recent
      data also suggest that colonization factors promote horizontal gene transfer of
      antimicrobial resistance genes by increasing the local density of Salmonella in
      colonized intestines. Although a profusion of genes are involved in Salmonella
      pathogenesis, the relative importance of their allelic variation has only been
      studied intensely in the type 1 fimbrial adhesin FimH. Although other Salmonella
      virulence factors demonstrate allelic variation, their association with specific
      metadata (e.g., host species, disease or carrier state, time and geographic place
      of isolation, antibiotic resistance profile, etc.) remains to be interrogated. To
      date, genome-wide association studies (GWAS) in bacteriology have been limited by
      the paucity of relevant metadata. In addition, due to the many variables amid
      metadata categories, a very large number of strains must be assessed to attain
      statistically significant results. However, targeted approaches in which genes of
      interest (e.g., virulence factors) are specifically sequenced alleviates the time
      consuming and costly statistical GWAS analysis and increases statistical power,
      as larger numbers of strains can be screened for non-synonymous single nucleotide
      polymorphisms (SNPs) that are associated with available metadata. Congruence of
      specific allelic variants with specific metadata from strains that have a
      relevant clinical and epidemiological history will help to prioritize functional
      wet-lab and animal studies aimed at determining cause-effect relationships. Such
      an approach should be applicable to other pathogens that are being collected in
      well-curated repositories. 

PMID- 24454312
TI  - Role of suppressors of cytokine signaling 3 in bone inflammatory responses.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is a potent regulator of cytokine
      signaling in macrophages and T cells. In recent studies, evidence has been
      provided for SOCS3 activation in all major bone cells including osteoclasts,
      chondrocytes, synoviocytes, and osteoblasts. The investigation of SOCS3 function
      in bone remodeling systems implicates SOCS3 as a key signaling molecule in bone
      cell-mediated inflammatory responses. Both pro- and anti-inflammatory functions
      of SOCS3 have been demonstrated in different types of bone cells. This review
      provides an overview of the important role of SOCS3 in inflammatory responses of
      various bone cells and in bone inflammatory disorders such as periodontal disease
      and arthritis. Understanding the roles of SOCS3 in inflammatory diseases of bone
      and joints such as arthritis, osteomyelitis, and periodontal diseases is critical
      to revealing insights into signaling pathways that can be manipulated in
      potential therapeutic approaches. 

PMID- 24454311
TI  - The Significance of Interferon-gamma in HIV-1 Pathogenesis, Therapy, and
      Prophylaxis.
AB  - Interferon-gamma (IFNgamma) plays various roles in the pathogenesis of HIV/AIDS.
      In an HIV-1 infected individual, the production of IFNgamma is detected as early
      as the acute phase and continually detected throughout the course of infection.
      Initially produced to clear the primary infection, IFNgamma together with other
      inflammatory cytokines are involved in establishing a chronic immune activation
      that exacerbates clinical diseases associated with AIDS. Unlike Type 1 IFNs,
      IFNgamma has no direct antiviral activity against HIV-1 in primary cultures, as
      supported by the in vivo findings of IFNgamma therapy in infected subjects.
      Results from both in vitro and ex vivo studies show that IFNgamma can instead
      enhance HIV-1 replication and its associated diseases, and therapies aimed at
      decreasing its production are under consideration. On the other hand, IFNgamma
      has been shown to enhance cytotoxic T lymphocytes and NK cell activities against
      HIV-1 infected cells. These activities are important in controlling HIV-1
      replication in an individual and will most likely play a role in the prophylaxis
      of an effective vaccine against HIV-1. Additionally, IFNgamma has been used in
      combination with HIV-1 vaccine to augment antiviral immunity. Technological
      advancements have focused on using IFNgamma as a biological marker to analyze the
      type(s) of immunity generated by candidate HIV vaccines and the levels of
      immunity restored by anti-retroviral drug therapies or novel immunotherapies.
      Hence, in addition to its valuable ancillary role as a biological marker for the
      development of effective HIV-1 prophylactic and therapeutic strategies, IFNgamma
      has a vital role in promoting the pathogenesis of HIV. 

PMID- 24454313
TI  - Dyslipidemia in patients with chronic and end-stage kidney disease.
AB  - In this review, we discuss the physiology, diagnosis and treatment of
      dyslipidemia in patients with chronic and end-stage renal disease. The recent
      important clinical trials in patients with chronic kidney disease and
      dyslipidemia are reviewed. Because of the lack of evidence in treating lipid
      abnormalities in this specific patient population, we propose that future studies
      should focus on the pathophysiological mechanisms and treatment of dyslipidemia
      in this special patient population. 

PMID- 24454315
TI  - Hemodynamic stabilizing effects of L-carnitine in chronic hemodialysis patients.
AB  - BACKGROUND: The effects of L-carnitine on the hemodynamic state of chronic
      hemodialysis patients have been debated. In order to clarify the effect of
      administered L-carnitine on cardiac function and hypotensive episodes during the
      hemodialysis procedure, a randomized double-blind placebo-controlled study was
      performed for 3 months. METHODS AND RESULTS: TWENTY STABLE OUTPATIENTS UNDERGOING
      HEMODIALYSIS TREATMENT WERE DIVIDED INTO TWO GROUPS: controls (placebo) and
      treated patients (L-carnitine 900 mg p.o. daily). After 3 months, cardiac
      function was reevaluated by echocardiography, and hypotensive episodes during
      hemodialysis were assessed. Free and acyl carnitine levels increased
      significantly from 22.3 +/- 7.1 to 140.3 +/- 57.5 MUmol/l and from 15.8 +/- 2.8
      to 94.8 +/- 50.4 MUmol/l, respectively, in the treated group. The ejection
      fraction significantly increased from 61.8 +/- 16.0 to 64.4 +/- 13.8% (p < 0.05)
      in the treated group. However, there was no difference in other echocardiographic
      parameters between the two groups. Hypotensive episodes significantly decreased
      from 4.0 +/- 1.7 to 1.3 +/- 0.9 times per month (p < 0.05), although patients'
      body weight did not change significantly. CONCLUSIONS: Beneficial effects of L
      carnitine on the hemodynamic state of chronic hemodialysis patients were
      observed. L-Carnitine supplementation might be considered especially for chronic
      hemodialysis patients with unstable hemodynamic conditions.

PMID- 24454314
TI  - Cardiac surgery-associated acute kidney injury.
AB  - Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious
      postoperative complication of cardiac surgery requiring cardiopulmonary bypass
      (CPB), and it is the second most common cause of AKI in the intensive care unit.
      Although the complication has been associated with the use of CPB, the etiology
      is likely multifactorial and related to intraoperative and early postoperative
      management including pharmacologic therapy. To date, very little evidence from
      randomized trials supporting specific interventions to protect from or prevent
      AKI in broad cardiac surgery populations has been found. The definition of AKI
      employed by investigators influences not only the incidence of CSA-AKI, but also
      the identification of risk variables. The advent of novel biomarkers of kidney
      injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the
      assessment of its severity and prognosis, and the early institution of
      interventions to prevent or reduce kidney damage. Further studies are needed to
      determine how to optimize cardiac surgical procedures, CPB parameters, and
      intraoperative and early postoperative blood pressure and renal blood flow to
      reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear
      efficacy in the prevention of CSA-AKI; however, some agents, such as the
      natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown
      promising results in renoprotection. It remains unclear whether CSA-AKI patients
      can benefit from the early institution of such pharmacologic agents or the early
      initiation of renal replacement therapy. 

PMID- 24454316
TI  - Uric Acid - key ingredient in the recipe for cardiorenal metabolic syndrome.
AB  - Elevated serum uric acid levels are a frequent finding in persons with obesity,
      hypertension, cardiovascular and kidney disease as well as in those with the
      cardiorenal metabolic syndrome (CRS). The increased consumption of a fructose
      rich Western diet has contributed to the increasing incidence of the CRS, obesity
      and diabetes especially in industrialized populations. There is also increasing
      evidence that supports a causal role of high dietary fructose driving elevations
      in uric acid in association with the CRS. Animal and epidemiological studies
      support the notion that elevated serum uric acid levels play an important role in
      promoting insulin resistance and hypertension and suggest potential
      pathophysiological mechanisms that contribute to the development of the CRS and
      associated cardiovascular disease and chronic kidney disease. To this point,
      elevated serum levels of uric acid appear to contribute to impaired nitric oxide
      production/endothelial dysfunction, increased vascular stiffness, inappropriate
      activation of the renin-angiotensin-aldosterone system, enhanced oxidative
      stress, and maladaptive immune and inflammatory responses. These abnormalities,
      in turn, promote vascular, cardiac and renal fibrosis as well as associated
      functional abnormalities. Small clinical trials have suggested that uric acid
      lowering therapies may be beneficial in such patients; however, a consensus on
      the treatment of asymptomatic hyperuricemia is lacking. Larger randomized
      controlled trials need to be performed in order to critically evaluate the
      beneficial effect of lowering serum uric acid in patients with the CRS and those
      with diabetes and/or hypertension. 

PMID- 24454318
TI  - Resurrection plants of the genus Ramonda: prospective survival strategies -
      unlock further capacity of adaptation, or embark on the path of evolution?
AB  - Paleoendemic species of the monophyletic genus Ramonda (R. myconi, R. serbica and
      R.~nathaliae) are the remnants of the Tertiary tropical and subtropical flora in
      Europe. They are the rare resurrection plants of Northern Hemisphere temperate
      zone. Ramonda serbica and R. nathaliae are chorologically differentiated in the
      Balkan Peninsula and occupy similar habitats in calcareous, northward slopes in
      canyons and mountainsides. They remain well-hydrated during spring, late autumn
      and even in winter. In summer and early autumn when plants are subjected to
      drought and thermal stress, their desiccation tolerance comes into operation and
      they fall into anabiosis. Investigations revealed the permanent presence of
      ubiquitine and its conjugates, high amounts of oxalic acid and proline. Both
      species are homoiochlorophyllous. It enables them to rapidly resume
      photosynthesis upon rehydration, but also makes them susceptible to reactive
      oxygen species formation. Dehydration induces activation of antioxidative enzymes
      (ascorbate peroxidase, glutathione reductase, polyphenol oxidase), increase in
      amounts of AsA and GSH, phenolic acids, dehydrins, sucrose, and inorganic ions.
      Plasma membranes, characterized by high amount of cholesterol, are subjected to
      decrease in membrane fluidity mostly on account of increased level of lipid
      saturation. Cytogenetic analysis revealed that R. nathaliae is a diploid (2n =
      48) and probably evolutionary older species, while R. serbica is a hexaploid (2n
      = 144). Two species live together in only two localities forming hybrid
      individuals (2n = 96). Polyploidization is the major evolutionary mechanism in
      the genus Ramonda that together with hybridization ability indicates that these
      relict species which have preserved an ancient survival strategy are not the
      evolutionary "dead end."The species of the genus Ramonda are promising sources of
      data important for understanding the complex strategy of resurrection plants'
      survival, appraised through a prism of their evolutionary and adaptive potential
      for multiple environmental stresses. 

PMID- 24454317
TI  - Using transcription of six Puccinia triticina races to identify the effective
      secretome during infection of wheat.
AB  - Wheat leaf rust, caused by the basidiomycete Puccinia triticina, can cause yield
      losses of up to 20% in wheat producing regions. During infection, the fungus
      forms haustoria that secrete proteins into the plant cell and effect changes in
      plant transcription, metabolism, and defense. It is hypothesized that new races
      emerge as a result of overcoming plant resistance via changes in the secreted
      effector proteins. To understand gene expression during infection and find
      genetic differences associated with races, RNA from wheat leaves infected with
      six different rust races, at 6 days post inoculation, was sequenced using
      Illumina. As P. triticina is an obligate biotroph, RNA from both the host and
      fungi were present and separated by alignment to the P. triticina genome and a
      wheat EST reference. A total of 222,571 rust contigs were assembled from 165
      million reads. An examination of the resulting contigs revealed 532 predicted
      secreted proteins among the transcripts. Of these, 456 were found in all races.
      Fifteen genes were found with amino acid changes, corresponding to putative
      avirulence effectors potentially recognized by 11 different leaf rust resistance
      (Lr) genes. Twelve of the potential avirulence effectors have no homology to
      known genes. One gene had significant similarity to cerato-platanin, a known
      fungal elicitor, and another showed similarity to fungal tyrosinase, an enzyme
      involved in melanin synthesis. Temporal expression profiles were developed for
      these genes by qRT-PCR and show that the genes expression patterns were
      consistent between races from infection initiation to just prior to spore
      eruption. 

PMID- 24454319
TI  - Unidirectional photodamage of pheophytin in photosynthesis.

PMID- 24454320
TI  - Could magnetic resonance provide in vivo histology?
AB  - THE DIAGNOSIS OF A SUSPECTED TUMOR LESION FACES TWO BASIC PROBLEMS: detection and
      identification of the specific type of tumor. Radiological techniques are
      commonly used for the detection and localization of solid tumors. Prerequisite is
      a high intrinsic or enhanced contrast between normal and neoplastic tissue.
      Identification of the tumor type is still based on histological analysis. The
      result depends critically on the sampling sites, which given the inherent
      heterogeneity of tumors, constitutes a major limitation. Non-invasive in vivo
      imaging might overcome this limitation providing comprehensive three-dimensional
      morphological, physiological, and metabolic information as well as the
      possibility for longitudinal studies. In this context, magnetic resonance based
      techniques are quite attractive since offer at the same time high spatial
      resolution, unique soft tissue contrast, good temporal resolution to study
      dynamic processes and high chemical specificity. The goal of this paper is to
      review the role of magnetic resonance techniques in characterizing tumor tissue
      in vivo both at morphological and physiological levels. The first part of this
      review covers methods, which provide information on specific aspects of tumor
      phenotypes, considered as indicators of malignancy. These comprise measurements
      of the inflammatory status, neo-vascular physiology, acidosis, tumor oxygenation,
      and metabolism together with tissue morphology. Even if the spatial resolution is
      not sufficient to characterize the tumor phenotype at a cellular level, this
      multiparametric information might potentially be used for classification of
      tumors. The second part discusses mathematical tools, which allow characterizing
      tissue based on the acquired three-dimensional data set. In particular, methods
      addressing tumor heterogeneity will be highlighted. Finally, we address the
      potential and limitation of using MRI as a tool to provide in vivo tissue
      characterization. 

PMID- 24454321
TI  - Potential benefits of Chinese Herbal Medicine for elderly patients with
      cardiovascular diseases.
AB  - Chinese Herbal Medicine (CHM), as the most common form of traditional Chinese
      medicine (TCM), has been playing an important role in the treatment of elderly
      cardiovascular diseases (CVDs) in China. In this paper, we briefly discuss on the
      potential benefits of CHM for elderly patients with CVDs. Initially, we summarize
      the characteristics of CVDs in the elderly, the present treatment of CVDs in the
      elderly, and the clinical applications of CHM for CVDs. Secondly, in addition to
      introducing the features of CHM, we discuss the differences between CHM and
      Western medicine. Lastly, the potential benefits of CHM are presented. We came to
      a conclusion that as mutual complementary, Western medicine and TCM together
      shall benefit the elderly patients with CVDs. 

PMID- 24454322
TI  - Impact of admission blood glucose levels on prognosis of elderly patients with ST
      elevation myocardial infarction treated by primary percutaneous coronary
      intervention.
AB  - OBJECTIVE: Admission hyperglycemia in acute myocardial infarction (MI) is related
      with increased in-hospital and long term mortality and major cardiac adverse
      events. We aimed to investigate how admission hyperglycemia affects the short and
      long term outcomes in elderly patients (> 65 years) after primary percutaneous
      coronary intervention for ST elevation myocardial infarction. METHODS: We
      retrospectively analyzed 677 consecutive elderly patients (mean age 72.2 +/-
      5.4). Patients were divided into two groups according to admission blood glucose
      levels. Group 1: low glucose group (LLG), glucose < 168 mg/dL; and Group 2: high
      glucose group (HGG), glucose > 168 mg/dL. RESULTS: In-hospital, long term
      mortality and in-hospital major adverse cardiac events were higher in the high
      admission blood glucose group (P < 0.001). Multivariate regression analysis
      showed: Killip > 1, post-thrombolysis in MI < 3 and admission blood glucose
      levels were independent predictors of in-hospital adverse cardiac events (P <
      0.001). CONCLUSIONS: Admission hyperglycemia in elderly patients presented with
      ST elevation myocardial infarction is an independent predictor of in-hospital
      major adverse cardiac events and is associated with in-hospital and long term
      mortality.

PMID- 24454323
TI  - Improvement in renal functions with transcatheter aortic valve implantation.
AB  - BACKGROUND & OBJECTIVES: In recent years, emerging transcatheter aortic valve
      implantation (TAVI) has become an alternative for surgery. However, with advanced
      age, several co-morbid factors together with contrast agent usage can cause
      deterioration in renal function and increase in the risk of acute kidney injury
      (AKI) with poor prognosis in patients with AKI. Therefore, many patients cannot
      benefit from this treatment. In this study, we aim to examine the effects of TAVI
      on renal functions. METHODS AND RESULTS: Seventy patients, mean age of 77.6
      years, underwent TAVI between July 2011 and December 2012. Estimated glomerular
      filtration rate (eGFR) was calculated by using the Cockcroft and Gault Formula.
      Patients were monitored for 48 h for urine output. Stage 1 AKI, according to the
      VARC-2 AKIN system, developed in only five (7.1%) of the patients after the
      procedure. There was a statistically significant increase between the mean 1(st)
      month eGFRs before (68.2 vs. 61.0, P < 0.01) and after (68.2 vs. 63.6, P < 0.05)
      the TAVI in the cohort. After TAVI (48.5 mL/min, P < 0.01) and the 1(st) month
      (52.1 mL/min, P < 0.01), the eGFR of the 36 (51.4%) patients diagnosed with
      chronic kidney disease before the procedure showed a statistically significant
      increase in renal functions. The hospital mortality rate was higher in the group
      which developed AKI (P < 0.01). First month eGFR showed a more statistically
      significant increase than pre-TAVI eGFR (62.8 and 69.8, P < 0.05, respectively)
      in AKI developing patients and this difference - though statistically not
      significant - continued into the sixth month. CONCLUSIONS: In this study, we
      showed that the treatment of aortic stenosis through TAVI allows improvement of
      renal functions, and that AKI rates will be lower with careful patient selection,
      proper pre-procedural hydration, and careful use of contrast agent.

PMID- 24454324
TI  - Recombinant tissue plasminogen activator plus heparin compared with heparin alone
      for patients with acute submassive pulmonary embolism: one-year outcome.
AB  - OBJECTIVE: To evaluate the long-term effects of thrombolysis on patients with
      submassive pulmonary embolism (PE). METHODS: Data of 136 patients with acute
      submassive PE and low risk of bleeding were prospectively collected from January
      2005 to October 2011 in a single medical center. Patients received recombinant
      tissue plasminogen activator (r-tPA) plus low molecular weight heparin (LMWH, TT
      group, n = 79) or LMWH alone (AT group, n = 57), depending on treating
      physician's recommendation and patient's preference. Echocardiography was
      performed at admission, 24 h, 6 and 12 months to evaluate right ventricular
      function. Computed tomography pulmonary angiography (CTPA) and lung perfusion
      scan were performed on admission, at 7 days, 6 and 12 months to evaluate clot
      burden. RESULTS: Seventy-nine patients received r-tPA plus LMWH (TT group) while
      57 received LMWH alone (AT group). The baseline characteristics and risk factors
      did not differ between the two groups. Respiratory rate, heart rate, and systolic
      blood pressure improved within two hours in both groups. Systolic pulmonary
      arterial pressure and tricuspid regurgitation improved to a greater extent in the
      TT group at 24 h, and at 12 months (P < 0.001), as compared to those in the AT
      group. At one week, and 12 months, clot burden decreased more in AT group, as
      compared to that in AT group (P < 0.001). There was no death due to bleeding in
      both groups. Recurrent PE were similar in both groups (2.5% in TT vs. 1.8% in
      AT). The rates of minor hemorrhages were 6.3% in TT group and 1.8% in AT group (P
      < 0.05). CONCLUSION: In submassive PE patient who has low risk of bleeding,
      thrombolysis plus anticoagulation can lead to greater improvement of right
      ventricular dysfunction and clot burden reduction as compared to anticoagulation
      therapy alone.

PMID- 24454325
TI  - Long-term clinical outcomes of drug-eluting stents vs. bare-metal stents in
      Chinese geriatric patients.
AB  - BACKGROUND & OBJECTIVE: Little is known about the relative efficacies of
      percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare
      metal stents (BMS) in elderly patients. The objective of this study was to
      evaluate the clinical outcome for geriatric patients who received either DES or
      BMS. METHODS: From January 2002 to October 2005, 199 consecutive Chinese
      geriatric patients (>= 75 years old) underwent PCI with coronary DES or BMS
      implantation at our institution. We analyzed the major clinical end points that
      included all-cause mortality, cardiovascular death, myocardial infarction, target
      lesion revascularization (TLR), stent thrombosis, and bleeding complications.
      RESULTS: The three-year cumulative rates of all-cause mortality, cardiovascular
      death, and myocardial infarction were significantly lower in the DES group (6.3%,
      3.6%, 5.4%) compared with the BMS group (16.2%, 11.5%, 14.9%; P < 0.05). No
      significant differences were found in the three-year cumulative rate for target
      lesion revascularization (6.3% vs. 4.6%, P = 0.61) or stent thrombosis (3.6% vs.
      2.3%, P = 0.70). Likewise, there were no statistically significant differences in
      the cumulative rate for intracranial hemorrhage, or major and minor hemorrhage at
      three years. CONCLUSIONS: DES-based PCI was associated with a significant
      reduction in the three-year cumulative rate of all-cause mortality,
      cardiovascular death, and myocardial infarction compared with BMS, without
      increased risk of TLR, stent thrombosis, or bleeding complications at three years
      in this group of Chinese geriatric patients.

PMID- 24454326
TI  - Comparison of coronary DES and BMS in octogenarians: A systematic review and meta
      analysis.
AB  - OBJECTIVE: Uncertainty exists regarding the relative performance of drug-eluting
      stents (DES) versus bare-metal stents (BMS) in octogenarians undergoing
      percutaneous coronary intervention (PCI). We undertook a meta-analysis to assess
      outcomes for DES and BMS in octogenarians undergoing PCI. METHODS: Electronic
      data bases of PubMed, Cochrane, and EMBASE were searched. We included randomized,
      controlled clinical trials (RCT) and observational studies comparing DES and BMS
      in octogenarians receiving PCI. The methodological qualities of eligible trials
      were assessed using a "risk of bias" tool. The endpoints included all-cause
      death, major adverse cardiac events (MACE), myocardial infarction (MI), target
      vessel revascularization (TVR), major bleeding, and stent thrombosis (ST). Odds
      ratios (OR) and 95% confidence intervals (95% CI) were calculated for each
      endpoint. RESULTS: A total of one RCT and six observational studies were included
      and analyzed in this meta-analysis. All trials were of acceptable quality. At 30
      days, compared with DES-treated patients, BMS-treated patients had a higher
      incidence of mortality (OR: 3.91, 95% CI: 1.10-13.91; P = 0.03). The OR for MACE
      (1.52, 95% CI: 0.56-4.17; P = 0.13), MI (0.81, 95% CI: 0.37-2.17; P = 0.23), TVR
      (0.75, 95% CI: 0.17-3.41; P = 0.41), major bleeding (0.77, 95% CI: 0.35-1.68; P =
      0.43), and ST (1.44, 95% CI: 0.32-6.45; P = 0.33) did not reach statistical
      significance. At one year follow-up, the OR did not favor BMS over MACE (MACE,
      defined as the composite of death, myocardial infarction, and TVR) (1.87; 95% CI:
      1.22-2.87; P < 0.01), MI (1.91, 95% CI: 1.22-2.99; P < 0.01), TVR (3.08, 95% CI:
      1.80-5.26; P < 0.01) and ST (3.37, 95% CI: 1.12-10.13; P < 0.01). The OR for
      mortality (1.51; 95% CI: 0.92-2.47; P = 0.10) and major bleeding (0.85, 95% CI:
      0.47-1.55; P = 0.60) did not reach statistical significance. At > 1 year follow
      up, the OR for all endpoints, including mortality, MACE, MI, TVR, major bleeding,
      and ST, did not reach statistical significance. CONCLUSIONS: Our meta-analysis
      suggests that DES is associated with favorable outcomes as compared with BMS in
      octogenarians receiving PCI.

PMID- 24454327
TI  - Relation of coronary collateral circulation with epicardial fat volume in
      patients with stable coronary artery disease.
AB  - OBJECTIVE: To investigated the relationship between epicardial fat volume (EFV)
      and coronary collateral circulation (CCC) in patients with stable coronary artery
      disease (CAD). METHODS: The study population consisted of 152 consecutive
      patients with CAD who underwent coronary angiography and were found to have at
      least 95% significiant lesion in at least one major coronary artery. EFV was
      assessed utilizing 64-multislice computed tomography. The patients were
      classifield into impaired CCC group (Group 1, Rentrop grades 0-1, n = 58), or
      adequate CCC (Group 2, Rentrop grades 2-3, n = 94). RESULTS: The EFV values were
      significantly higher in paitients with adequate CCC than in those with impaired
      CCC. In multivariate logistic regression analysis, EFV (OR = 1.059; 95% CI: 1.035
      1.085; P = 0.001); and presence of angina were independent predictors of adequate
      CCC. In receiver-operating characteristic curve analysis, the EFV value > 106.5
      mL yielded an area under the curve value of 0.84, with the test sensitivity of
      49.3%, and with 98.3% specifity. CONCLUSIONS: High EFV, and the presence of
      angina independently predict adequate CCC in patients with stable coronary artery
      disease. This association offers new diagnostic opportinities to assess
      collateral flow by conventional ultrasound techniques.

PMID- 24454328
TI  - Is combined lipid-regulating therapy safe and feasible for the very old patients
      with mixed dyslipidemia?
AB  - OBJECTIVES: To detect the efficacy and safety of combined lipid-regulating
      therapies in the very old patients with mixed dyslipidemia and determine an
      appropriate therapy for them. METHODS: Four hundred and fifty patients aged over
      75 with mixed dyslipidemia were divided into five groups according to different
      combination therapies. Lipid levels and drug related adverse events were tested
      during the study. RESULTS: Total cholesterol (TC) and low-density lipoprotein
      cholesterol (LDL-C) levels were reduced in every group compared to baseline:
      statin + ezetimibe: -30.0% and -55.5%; statin + policosanol: -31.1% and -51.2%;
      statin + fibrates: -23.7% and -44.6%; statin + niacin: -25.2% and -43.0%; and
      niacin + fibrates: -11.3% and -23.5%. The target achievement rates of LDL-C all
      exceeded 50%, except in niacin + fibrates (42.0%); statin + ezetimibe: 57.0%;
      statin + policosanol: 56.0%; statin + niacin: 52.0%; and statin + fibrates:
      50.0%. However, overall, the niacin + fibrates group was the most effective in
      decreasing triglyceride (TG) and increasing high-density lipoprotein cholesterol
      (HDL-C) as follows: niacin + fibrates: -39.3% and 28.6%; statin + fibrates: 
      29.3% and 18.4%; statin + niacin: -18.5% and 16.7%; statin + ezetimibe: -17.1%
      and 7.1%; and statin + policosanol: -15.6% and 9.5%. The achievement rates of TG
      and HDL-C levels in niacin + fibrates (58.0% and 39.0%) were better than the
      other four groups: statin + niacin (34.0% and 34.0%), statin + fibrates (43.0%
      and 28.0%), statin + policosanol (30.0% and 24.0%) and statin + ezetimibe (28.0%
      and 25.0%). Patients in all five groups experiencing drug adverse events were
      only 2% and no severe adverse events occurred. CONCLUSIONS: Statin + ezetimibe
      was the most effective group in lowering TC and LDL-C levels, while niacin +
      fibrates was the most effective in decreasing TG and increasing HDL-C levels. The
      commonly used combined lipid-regulating therapies with common dosages in this
      study were all quite safe and feasible for the very old patients with mixed
      hyperlipidemia.

PMID- 24454329
TI  - High-dose atorvastatin pretreatment could diminishes microvascular impairment in
      patients undergoing elective percutaneous coronary intervention.
AB  - OBJECTIVES: High-dose statins pretreatment is reasonable before percutaneous
      coronary intervention (PCI) to reduce the risk of periprocedural myocardial
      injury. However, the mechanism underlying this protective effect has not been
      elucidated. The aim of this study is to evaluate the effects of high-dose
      atorvastatin pretreatment on microvascular function and myocardial injury after
      elective PCI. METHODS: Eighty four patients underwent elective PCI were randomly
      assigned to high-dose atorvastatin (40 mg/d) and low-dose atorvastatin (20 mg/d)
      treatment for 7 days before PCI. The index of microcirculatory resistance (IMR)
      was measured by an intracoronary ressure/temperature sensor-tipped guidewire at
      maximal hyperemia after PCI. Fractional flow reserve (FFR) was measured before
      and after procedure. Troponin I levels were obtained at baseline and 20-24 h
      after procedure. RESULTS: IMR values were significantly lower in high-dose group
      when compared to low-dose group (16.5 +/- 6.1 vs. 31.2 +/- 16.0, P < 0.001). Pre
      PCI troponin I levels between the two groups were similar (0.028 +/- 0.05 vs.
      0.022 +/- 0.04, P = 0.55). However, post-PCI troponin I levels in high-dose group
      were significantly lower than low-dose group (0.11 +/- 0.02 vs. 0.16 +/- 0.09, P
      < 0.001). Multivariate analysis identified maximum inflation pressure > 20 atm as
      an independent predictor of IMR > 32 (Odds ratio (OR): 3.3, 95% confidence
      intervals (95%CI): 1.3-8.5, P = 0.02). High-dose atorvastatin was the only
      independent protective factor of IMR > 32 (OR: 0.29, 95%CI: 0.11-0.74, P = 0.01).
      CONCLUSIONS: The present study confirmed that diminishing microvascular
      impairment is one of the mechanism underlying protecting effect of high-dose
      statins pretreatment from myocardial injury during PCI. These suggest that high
      dose statin pretreatment is reasonable in patients undergoing elective PCI.

PMID- 24454330
TI  - Dyslipidemia in rat fed with high-fat diet is not associated with PCSK9-LDL
      receptor pathway but ageing.
AB  - BACKGROUND: Obesity is associated with unfavorable alternations in plasma lipid
      profile and a broad spectrum of cardio-metabolic disorders. Proprotein convestase
      subtilisin kexin type 9 (PCSK9) is a novel circulating protein that promotes
      hypercholesterolemia by decreasing hepatic low lipoprotein density receptor
      (LDLR) protein. However, the relationship between PCSK9 concentration and lipid
      profile in an obesity condition has less been investigated. OBJECTIVE: To examine
      the changes of plasma PCSK9 concentration in a rat model fed with high fat diet
      (HFD) and its correlation to lipid profile, body weight and ageing. METHODS:
      Twenty male Sprague Dawley (SD) rats were divided into two groups, control group
      (fed with normal pellet for 4 weeks), and high-fat diet group (fed with 3%
      cholesterol enrich diet for 4 weeks). Blood samples of rats were obtained before
      and at days 14, 21, and 28 in both groups. The body weight, plasma metabolic
      parameters (glucose, lipid profile) and PCSK9 were determined at indicated time
      points. RESULTS: The body weights were significantly increased in rats fed with
      HFD compared to that in rats with normal pellets at day 28. Additionally, total
      cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL
      C) levels in rat fed with HFD were also higher than that in rats fed with control
      diet while decreased high density lipoprotein cholesterol (HDL-C) levels were
      found in rats with HFD at day 28. More interesting, there were no differences of
      plasma PCSK9 concentrations as well as hepatic expression of LDLR between the two
      groups at day 28. CONCLUSIONS: Although the body weight and LDL-C were
      significantly increased in rats fed with HFD at 4 weeks, there were no
      differences of changes in plasma PCSK9 concentration and LDLR expression of liver
      tissue in both groups at baseline and day 28, suggesting that dyslipidemia in the
      rat model with HFD appears not to be associated with PCSK9-LDLR pathway but
      ageing.

PMID- 24454331
TI  - Heart failure with preserved ejection fraction.
AB  - Progressive aging of the population and prolongation of life expectancy have led
      to the rising prevalence of heart failure (HF). Despite the improvements in
      medical therapy, the mortality rate of this condition has remained unacceptably
      high, becoming the primary cause of death in the elderly population. Almost half
      of patients with signs and symptoms of HF are found to have a nearly normal
      ejection fraction, which delineates a distinct clinical syndrome, known as HF
      with preserved ejection fraction (HF-PEF). While early research focused on the
      importance of diastolic dysfunction, more recent studies reported the
      pathophysiological complexity of the disease with multiple cardiovascular
      abnormalities contributing to its development and progression. HF-PEF is a
      challenging major health problem with yet no solution as there is no evidence
      based treatment which improves clinical outcomes. This review summarizes the
      state of current knowledge on diagnosis, prognosis and treatment of HF-PEF, with
      particular insights on the pathological characteristics in the elderly
      population. 

PMID- 24454333
TI  - Coarctation of aorta with complete aortic occlusion.
AB  - Survival to advanced age is exceptional in patients with unrepaired aortic
      coarctation. We report the case of an 81-year-old man with aortic coarctation and
      total occlusion who was otherwise asymptomatic. Coarctation was suspected when a
      femoral-radial pulse delay was noted during his routine physical examination. A
      70-mmHg systolic blood pressure gradient between the upper and lower extremities
      was detected. Subsequent magnetic resonance angiography, aortography, and
      coronary angiography revealed severe coarctation of the aorta, well-developed
      collateral vessels, and severe coronary artery disease. A staged percutaneous
      coronary intervention procedure was performed and the coarctation was managed
      conservatively with antihypertensive medication. 

PMID- 24454332
TI  - Role of estrogen in angiogenesis in cardiovascular diseases.
AB  - The formation of new blood vessels from existing ones is a major process of
      angiogenesis and it is most effective in the vascular systems. The physiological
      process like hypoxia inducible factors involved in the regeneration of damaged
      tissues varies within the vascular systems in the endothelium and could be
      limited due to some major angiogenic growth factors like vascular endothelial
      growth factor, fibroblast growth factors and epidermal growth factor among others
      which bring about this cellular vascular regrowth. These physiological processes
      leading to cellular vascular regrowth could be a major function for the treatment
      of cardiovascular diseases such as ischemia and atherosclerosis. Estrogens are
      one of the known factors within the cellular mechanisms that could initiate
      repairs to the damaged vascular tissues, since estrogens are known inducers of
      angiogenesis leading to this cellular regrowth. Research has also shown that this
      cellular regrowth is induced by vascular angiogenic growth factors via the
      estrogen receptors. In this review we will attempt to summarize the main
      angiogenic growth factors involved in these physiological processes leading to
      angiogenesis and possible new mechanisms that could lead to this vascular
      regrowth. And also we will try to summarize some reports on the effect of
      estrogen on these physiological processes leading to angiogenesis in
      cardiovascular diseases. 

PMID- 24454334
TI  - An Investigation of Calibration Phantoms for CT Scanners with Tube Voltage
      Modulation.
AB  - The effects of calibration phantoms on the correction results of the empirical
      artifacts correction method (ECCU) for the case of tube modulation were
      investigated. To improve the validity of the ECCU method, the effect of the
      geometry parameter of a typical single-material calibration phantom (water
      calibration phantom) on the ECCU algorithm was investigated. Dual-material
      calibration phantoms (such as water-bone calibration phantom), geometry
      arrangement, and the area-ratio of dual-material calibration phantoms were also
      studied. Preliminary results implied that, to assure the effectiveness of the
      ECCU algorithm, the polychromatic projections of calibration phantoms must cover
      the polychromatic projection data of the scanning object. However, the projection
      range of a water calibration phantom is limited by the scan field of view (SFOV),
      thus leading to methodological limitations. A dual-material phantom of a proper
      size and material can overcome the limitations of a single-material phantom and
      achieve good correction effects. 

PMID- 24454335
TI  - Effects of PPAR gamma Agonist Pioglitazone on Redox-Sensitive Cellular Signaling
      in Young Spontaneously Hypertensive Rats.
AB  - PPAR gamma receptor plays an important role in oxidative stress response. Its
      agonists can influence vascular contractility in experimental hypertension. Our
      study was focused on the effects of a PPAR gamma agonist pioglitazone (PIO) on
      blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling
      at the central (brainstem, BS) and peripheral (left ventricle, LV) levels in
      young prehypertensive rats. 5-week-old SHR were treated either with PIO (10
      mg/kg/day, 2 weeks) or with saline using gastric gavage. Administration of PIO
      significantly slowed down blood pressure increase and improved lipid profile and
      aortic relaxation after insulin stimulation. A significant increase in PPAR gamma
      expression was found only in BS, not in LV. PIO treatment did not influence NOS
      changes, but had tissue-dependent effect on SOD regulation and increased SOD
      activity, observed in LV. The treatment with PIO differentially affected also the
      levels of other intracellular signaling components: Akt kinase increased in the
      the BS, while beta -catenin level was down-regulated in the BS and up-regulated
      in the LV. We found that the lowering of blood pressure in young SHR can be
      connected with insulin sensitivity of vessels and that beta -catenin and SOD
      levels are important agents mediating PIO effects in the BS and LV. 

PMID- 24454336
TI  - Pseudoginsenoside F11, a Novel Partial PPAR gamma Agonist, Promotes Adiponectin
      Oligomerization and Secretion in 3T3-L1 Adipocytes.
AB  - PPAR gamma is a nuclear hormone receptor that functions as a master regulator of
      adipocyte differentiation and development. Full PPAR gamma agonists, such as the
      thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes.
      However, they are characterized by undesirable side effects due to their strong
      agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type
      ginsenoside isolated from Panax quinquefolium L. (American ginseng). In this
      study, we found that p-F11 activates PPAR gamma with modest adipogenic activity.
      In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1
      adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of
      PPAR gamma at Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPAR gamma
      agonist, which might have the potential to be developed as a new PPAR gamma 
      targeted therapeutics for type 2 diabetes. 

PMID- 24454337
TI  - Performance of Routine Helicobacter pylori Invasive Tests in Patients with
      Dyspepsia.
AB  - Background. This study was designed to compare the accuracy of three different
      invasive methods for the detection of Helicobacter pylori (H. pylori) infection
      in patients with dyspepsia. These tests included culture, histology, and the
      rapid urease test (CLO test). Methods. H. pylori infection was diagnosed
      prospectively in 246 untreated dyspeptic patients who underwent upper
      gastrointestinal endoscopy. The gold standard for H. pylori infection was based
      on a positive culture or both a positive histological examination and a CLO test.
      Results. H. pylori was diagnosed in 33.3% of the patients. The sensitivity,
      specificity, positive predictive value, negative predictive value, and overall
      accuracy were as follows: histology from the antrum (95.12; 95.12; 90.7; 97.5;
      95.12%); histology from the antrum and corpus (95.12; 95.12; 90.7; 97.5; 95.12%);
      histology from the corpus (76.83; 96.95; 92.65; 89.33; 90.24%); culture (91.46;
      100; 100; 95.91; 97.15%); a CLO test from the antrum and corpus (85.59; 100; 100;
      93.71; 95.52%); a CLO test from the antrum (64.63; 100; 100; 84.97; 88.21%); a
      CLO test from the corpus (69.51; 100; 100; 96.77; 89.83%), respectively.
      Conclusions. Antral biopsy histology and culture are the best methods for the
      diagnosis of H. pylori infection in our cohort of patients with dyspepsia. 

PMID- 24454338
TI  - Bariatric surgery in moderately obese patients: a prospective study.
AB  - Introduction. Moderate obesity (BMI 30-35 kg/m(2)) affects 25% of the western
      population. The role of bariatric surgery in this context is currently debated,
      reserved for patients with comorbidity, as an alternative to conservative medical
      treatment. We describe our experience in moderately obese patients treated with
      bariatric surgery. Materials and Methods. Between September 2011 and September
      2012, 25 patients with grade I obesity and comorbidities underwent bariatric
      surgery: preoperative mean BMI 33.2 kg/m(2), 10 males, mean age 42 years. In
      presence of type 2 diabetes mellitus (T2DM) (56%), gastric bypass was performed;
      in cases with hypertension (64%) and obstructive sleep apnea (OSA) (12%), sleeve
      gastrectomy was performed. All operations were performed laparoscopically.
      Results. Mean follow-up was 12.4 months. A postoperative complication occurred:
      bleeding from the trocar site was resolved with surgery in local anesthesia.
      Reduction in average BMI was 6 points, with a value of 27.2 kg/m(2). Of the 14
      patients with T2DM, 12 (86%) discontinued medical therapy because of a
      normalization of glycemia. Of the 16 patients with arterial hypertension, 14
      (87%) showed remission and 2 (13%) improvement. Complete remission was observed
      in patients with OSAS. Conclusions. The results of our study support the validity
      of bariatric surgery in patients with BMI 30-35 kg/m(2). Our opinion is that, in
      the future, bariatric surgery could be successful in selected cases of moderately
      obese patients. 

PMID- 24454340
TI  - Novel molecular targets in malignant diseases of digestive system.

PMID- 24454339
TI  - The economic impact of weight regain.
AB  - Background. Obesity is well known for being associated with significant economic
      repercussions. Bariatric surgery is the only evidence-based solution to this
      problem as well as a cost-effective method of addressing the concern. Numerous
      authors have calculated the cost effectiveness and cost savings of bariatric
      surgery; however, to date the economic impact of weight regain as a component of
      overall cost has not been addressed. Methods. The literature search was conducted
      to elucidate the direct costs of obesity and primary bariatric surgery, the rate
      of weight recidivism and surgical revision, and any costs therein. Results. The
      quoted cost of obesity in Canada was $2.0 billion-$6.7 billion in 2013 CAD. The
      median percentage of bariatric procedures that fail due to weight gain or
      insufficient weight loss is 20% (average: 21.1% +/- 10.1%, range: 5.2-39, n =
      10). Revision of primary surgeries on average ranges from 2.5% to 18.4%, and
      depending on the procedure accounts for an additional cost between $14,000 and
      $50,000 USD per patient. Discussion. There was a significant deficit of the
      literature pertaining to the cost of revision surgery as compared with primary
      bariatric surgery. As such, the cycle of weight recidivism and bariatric
      revisions has not as of yet been introduced into any previous cost analysis of
      bariatric surgery. 

PMID- 24454341
TI  - Effect of physician-delivered patient education on the quality of bowel
      preparation for screening colonoscopy.
AB  - Background. Inadequate bowel preparation is common in outpatients undergoing
      screening colonoscopy because of unawareness and poor adherence to instruction.
      Methods. Herein, 105 consecutive outpatients referred for screening colonoscopy
      were enrolled in this prospective, colonoscopist-blinded study. The patients were
      assigned to an intensive-education group, with 10 minutes of physician-delivered
      education, or to standard care. At the time of colonoscopy, the quality of bowel
      preparation was assessed using the Boston Bowel Preparation Scale (BBPS). The
      primary outcome was a BBPS score >=5. The secondary outcomes were the mean BBPS
      score, insertion time, adenoma detection rate, and number of adenomas detected.
      Results. We analyzed 39 patients who received intensive education and 60
      controls. The percentage of adequate bowel preparations with a BBPS score >=5 was
      higher in the intensive-education group than in the control group (97.4% versus
      80.0%; P = 0.01). The adjusted odds ratio for having a BBPS score >=5 in the
      intensive-education group was 10.2 (95% confidence interval = 1.23-84.3; P =
      0.03). Other secondary outcomes were similar in the 2 groups. Conclusions.
      Physician-delivered education consisting of a brief counseling session in
      addition to written instructions improves the quality of bowel preparation in
      outpatients undergoing screening colonoscopy. 

PMID- 24454342
TI  - (18)F-FLT PET/CT in Patients with Gastric Carcinoma.
AB  - The aim of the study was to evaluate the usefulness of 18F-FLT PET/CT in the
      detection and differentiation of gastric cancers (GC). 104 consecutive patients
      (57 cases of adenocarcinoma tubulare (G2 and G3), 17 cases of mucinous
      adenocarcinoma, 6 cases of undifferentiated carcinoma, 14 cases of adenocarcinoma
      partim mucocellulare, and 10 cases of end stage gastric cancer) with newly
      diagnosed advanced gastric cancer were examined with FLT PET/CT. For quantitative
      and comparative analyses, the maximal standardized uptake value (SUVmax) was
      calculated for both the tumors and noninvaded gastric wall. Results. There were
      found, in the group of adenocarcinoma tubulare, SUVmax 1.5-23.1 (7.46 +/- 4.57),
      in mucinous adenocarcinoma, SUVmax 2.3-10.3 (5.5 +/- 2.4), in undifferentiated
      carcinoma, SUVmax 3.1-13.6 (7.28 +/- 3.25), in adenocarcinoma partim
      mucocellulare, SUVmax 2-25.3 (7.7 +/- 6.99), and, in normal gastric wall, SUVmax
      1.01-2.55 (1.84 +/- 0.35). For the level of 2.6 cut-off value between the normal
      wall and neoplasm FLT uptake from ROC analysis, all but five gastric cancers
      showed higher accumulation of FLT than noninfiltrated mucosa. Conclusion. Gastric
      cancer presents higher accumulation of 18F-FLT than normal, distended gastric
      mucosa. Significantly higher accumulation was shown in cancers better
      differentiated and with higher cellular density. 

PMID- 24454343
TI  - Highlights in IBD Epidemiology and Its Natural History in the Paediatric Age.
AB  - Background. The number of patients of all age brackets diagnosed with
      Inflammatory Bowel Disease (IBD) has risen dramatically worldwide over the past
      50 years. IBD's changing epidemiology suggests that environmental factors play a
      major role in modifying disease expression. Aim. To review studies carried out
      worldwide analyzing IBD epidemiology. Methods. A Medline search indicating as
      keywords "Inflammatory Bowel Disease," "epidemiology," "natural history,"
      "Crohn's Disease," "Ulcerative Colitis," and "IBD Unclassified" was performed. A
      selection of clinical cohort and systematic review studies that were carried out
      between 2002 and 2013 was reviewed. Studies referring to an earlier date were
      also considered whenever the data were relevant to our review. Results. The
      current mean prevalence of IBD in the total population of Western countries is
      estimated at 1/1,000. The highest prevalence and incidence rates of IBD worldwide
      are reported from Canada. Just as urbanization and socioeconomic development, the
      incidence of IBD is rising in China. Conclusions. Multicenter national registers
      and international networks can provide information on IBD epidemiology and lead
      to hypotheses about its causes and possible management strategies. The rising
      trend in the disease's incidence in developing nations suggests that its
      epidemiological evolution is linked to industrialization and modern Westernized
      lifestyles. 

PMID- 24454344
TI  - Effect of Di(2-ethylhexyl)phthalate on Helicobacter pylori-Induced Apoptosis in
      AGS Cells.
AB  - Plastic products are wildly used in human life. Di(2-ethylhexyl)phthalate (DEHP)
      is an essential additive in plastic manufacturing and is used as plasticizer for
      many products including plastic food packaging. DEHP is a teratogenic compound
      and can cause potent reproductive toxicity. DEHP can also cause liver damage,
      peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated
      with peptic ulcers and gastric cancer; however, the underlying effect and
      mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral
      infection route of H. pylori parallels the major ingestion route of DEHP into the
      human body. Therefore, we wanted to study the effect of DEHP and H. pylori
      exposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma).
      The viability of the AGS cell line was significantly lower in 80  MU M-DEHP and
      H. pylori (MOI = 100 : 1) coexposure than DEHP or H. pylori alone. DEHP and H.
      pylori coexposure also induced caspase-3 activation, and increased Bax/Bcl-2
      ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can
      enhance H. pylori cytotoxicity and induce gastric epithelial cell apoptosis.
      Therefore, it is possible that DEHP and H. pylori coexposure might enhance the
      disruption of the gastric mucosa integrity and potentially promote the
      pathogenesis of gastric carcinogenesis. 

PMID- 24454345
TI  - The potential benefits and adverse effects of phytic Acid supplement in
      streptozotocin-induced diabetic rats.
AB  - In this study, the effect of phytic acid supplement on streptozotocin-induced
      diabetic rats was investigated. Diabetic rats were fed rodent chow with or
      without phytic acid supplementation for thirty days. Blood and organ samples were
      collected for assays. The average food intake was the highest and the body weight
      gain was the lowest in the group fed phytic acid supplement compared to the
      diabetic and normal control groups. There was a downward trend in intestinal
      amylase activity in the group fed phytic acid supplement compared to the other
      groups. The spike in random blood glucose was the lowest in the same group. We
      noted reduced serum triglycerides and increased total cholesterol and HDL
      cholesterol levels in the group fed phytic acid supplement. Serum alkaline
      phosphatase and alanine amino transferase activities were significantly (P <
      0.05) increased by phytic acid supplementation. Systemic IL-1 beta level was
      significantly (P < 0.05) elevated in the diabetic control and supplement treated
      groups. The liver lipogenic enzyme activities were not significantly altered
      among the groups. These results suggest that phytic acid supplementation may be
      beneficial in the management of diabetes mellitus. The observed adverse effect on
      the liver may be due to the combined effect of streptozotocin-induced diabetes
      and phytic acid supplementation. 

PMID- 24454346
TI  - The genus spilanthes ethnopharmacology, phytochemistry, and pharmacological
      properties: a review.
AB  - Spilanthes spp. are popular, over-the-counter remedies; they are sold over the
      internet under various names and are widely used in traditional medicine in
      various cultures. This review will summarize the important reports on the
      ethnopharmacology, botany, phytochemistry, and pharmacological properties as
      described in the literature from recent years (1920 to 2013). Spilanthes spp. are
      used for more than 60 types of disorders. They are reported to contain a number
      of biologically active phytochemicals, although a large number of
      ethnopharmacological uses have been documented; only a few of these species have
      been investigated for their chemical and biological activities. The studies are
      carried out mainly on Spilanthes extracts and a few metabolites substantiate the
      uses of these plants in traditional medicine. Well-conducted pharmacological
      studies are still needed for several traditional indications, and the mechanisms
      of action by which the plant extracts and the active compounds exert their
      pharmacological effects remain to be studied. They are predominantly used as
      extracts in personal care products, traditional medicines, and the pharmaceutical
      and culinary areas. Suggestions are made regarding some of the possible
      mechanisms of action as to how the known compounds may exert their biological
      activity. 

PMID- 24454347
TI  - Antioxidant potential of a polyherbal antimalarial as an indicator of its
      therapeutic value.
AB  - Nefang is a polyherbal product composed of Mangifera indica (bark and leaf),
      Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum
      gratissimum (leaves), used for the treatment of malaria. Compounds with
      antioxidant activity are believed to modulate plasmodial infection. Antioxidant
      activity of the constituent aqueous plants extracts, in vitro, was evaluated
      using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic content (TPC), and
      ferric reducing antioxidant power (FRAP) methods and, in vivo, Nefang (100 and
      500 mg kg(-1)) activity was evaluated in carbon tetrachloride-induced oxidative
      stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid
      peroxidation by the malondialdehyde and total proteins assays were carried out.
      P. guajava, M. indica leaf, and bark extracts had the highest antioxidant
      properties in all three assays, with no statistically significant difference.
      Rats treated with the carbon tetrachloride had a statistically significant
      decrease in levels of triglycerides, superoxide dismutase, and catalase (P <
      0.05) and increase in malondialdehyde activity, total protein levels, and liver
      and renal function markers, whereas rats treated with Nefang showed increased
      levels in the former and dose-dependent decrease towards normal levels in the
      later. These results reveal the constituent plants of Nefang that contribute to
      its in vivo antioxidant potential. This activity is a good indication of the
      therapeutic potential of Nefang. 

PMID- 24454348
TI  - Comparative Evaluation of Anti-Inflammatory Activity of Curcuminoids, Turmerones,
      and Aqueous Extract of Curcuma longa.
AB  - Curcuma longa is widely known for its anti-inflammatory activity in traditional
      system of medicine for centuries and has been scientifically validated
      extensively. The present study was conducted to evaluate the anti-inflammatory
      activity of curcuminoids and oil-free aqueous extract (COFAE) of C. longa and
      compare it with that of curcuminoids and turmerones (volatile oil), the bioactive
      components of C. longa that are proven for the anti-inflammatory potential. The
      activity against inflammation was evaluated in xylene-induced ear edema, cotton
      pellet granuloma models in albino Swiss mice and albino Wistar rats,
      respectively. The results showed that COFAE of C. longa at three dose levels
      significantly (P <= 0.05) inhibited inflammation in both models, as evidenced by
      reduction in ear weight and decrease in wet as well as dry weights of cotton
      pellets, when compared to the vehicle control. The COFAE of C. longa showed
      considerable anti-inflammatory effects against acute and chronic inflammation and
      the effects were comparable to those of curcuminoids and turmerones. 

PMID- 24454349
TI  - Adherence of surgeons to antimicrobial prophylaxis guidelines in a tertiary
      general hospital in a rapidly developing country.
AB  - Objectives. To assess the standard practice of care of surgeons regarding
      surgical antibiotic prophylaxis, to identify gaps, and to set recommendations.
      Methods. A retrospective analysis of data obtained from different surgical units
      in a single center in Qatar over a 3-month period in 2012. A total of 101
      patients who underwent surgery and followed regimes for surgical prophylaxis as
      per hospital guidelines were included in the study. Results. The overall use of
      antibiotic was 89%, whereas the current practice did not match the recommended
      hospital protocols in 53.5% of cases. Prolonged antibiotics use (59.3%) was the
      commonest reason for nonadherence followed by the use of an alternative
      antibiotic to that recommended in the protocol (31.5%) and no prophylaxis was
      used in 9.2% of cases. The rate of compliance was significantly higher among
      clean surgery than clean contaminated group (P = 0.03). Forty-four percent of
      clean and 65% of clean-contaminated procedures showed noncompliance with the
      recommended surgical antimicrobial prophylaxis hospital guidelines. Conclusion.
      Lack of adherence to hospital protocols is not uncommon. This finding remains a
      challenge to encourage clinicians to follow hospital guidelines appropriately and
      to consistently apply the surgical antibiotic prophylaxis. The role of clinical
      pharmacist may facilitate this process across all surgical disciplines. 

PMID- 24454350
TI  - Influence of preoperative pain duration on microsurgical varicocelectomy
      outcomes.
AB  - Objective. To investigate the question of whether duration of pain before surgery
      ultimately affects sperm parameters after varicocelectomy. Methods. Fifty
      patients with painful grade-3 varicocele were investigated prospectively. The
      patients were divided into two groups according to their symptom period. The
      patients having had grade-3 varicocele for less than 1 year were included in
      Group-1 (Ge, n = 25). Twenty-five patients who had painful grade-3 varicocele for
      more than 1 year (Gs, n = 25) were classified in Group-2. Semen analysis was
      performed after 3 days of sexual abstinence twice a month. Total sperm
      concentration (TSC), rapidly progressive motility (SPa), and slow or sluggish
      motility (SPb) rates were noted. Pain was evaluated by using 10 cm visual
      analogue scale (VAS). Results. Postoperative TSC and %SPb were significantly
      higher in both groups (P = 0.01). There was no difference between two groups for
      preoperative and postoperative TSC, %SPa, % and SPb values. VAS significantly
      declined in both groups (P = 0.005). This postoperative decline was not
      significant for intergroup comparison. Conclusions. Our results show that
      increase in semen quality and decrease in the pain after microsurgery
      varicocelectomy do not depend on the duration of the preoperative pain. 

PMID- 24454351
TI  - Urolastic-a new bulking agent for the treatment of women with stress urinary
      incontinence: outcome of 12 months follow up.
AB  - Objective. To evaluate the efficacy and safety of the new injectable implant,
      Urolastic, in women with stress urinary incontinence (SUI) after 12-month
      followup. Materials and Methods. A prospective, cohort study included adult women
      with SUI. Patients were treated with Urolastic periurethral injections under
      local anaesthesia. The injection procedure was repeated after 6 weeks when
      indicated. Patients were evaluated for efficacy and safety parameters 6 weeks, 3
      months, and 12 months after therapy. Results. Twenty women 56 (33-71) years old
      were included. Thirteen patients (65%) received one injection each (overall
      average of 2,1 mL); 7 patients (35%) received a second injection. Nineteen
      patients complete the 12-month followup. The mean Stamey incontinence grade
      significantly decreased from 1.9 at baseline to 0.4 at 12 months (visit IV) (P <
      0.001). None of the patients were dry at baseline; 68% of them were dry at 12
      months. The mean number of incontinence episodes significantly decreased from
      6/day at baseline to 1.6/day at visit IV (P < 0.001). Reduction in pad weight
      went from 20.2 to 7.8 g at one year. The mean I-QoL score significantly increased
      from 51 at baseline to 76 at visit IV (P < 0.001). Six patients (30%) developed
      minor complications related to the injection procedure. Conclusions. Urolastic is
      effective and long-standing urethral bulking agent with moderate adverse events. 

PMID- 24454352
TI  - Epididymoorchitis as the first finding in patients with brucellosis.
AB  - Purpose. Acute scrotal pain as the first symptom of brucellosis is rarely
      observed. We aimed to evaluate the data of male patients with brucellosis and
      epididymoorchitis as the initial diagnosis. Material and Methods. The data of
      seven patients presented with testicular pain, hyperemia, swelling, and increased
      fever were reviewed. Concomitant focal diseases as well as clinical, laboratory,
      and radiological findings were retrospectively evaluated. Results. The mean age
      of the patients was 22.28 +/- 7.78 (16-35) years. All patients presented with
      scrotal pain, swelling, and increased sweating. Additional findings included
      fever, asthenia, arthralgia, dysuria, shiver and rash, weight loss, and vomiting
      in 6, 5, 4, 4, 3, 2, and 1 patient, respectively. In all of 7 patients, the
      agglutination tests of Rose-Bengal and Wright were positive. Coombs test was
      positive only in 3 patients. The patients underwent antibiotic and conservative
      treatment. No relapse was observed following the treatment. Conclusion. In
      endemic regions, epididymoorchitis caused by brucellosis should be considered in
      the differential diagnosis of patients presenting with acute scrotal pain.
      Clinical and serological findings are sufficient for the diagnosis. Conservative
      management combined with antibiotic therapy is adequate for managing brucellar
      epididymoorchitis. 

PMID- 24454353
TI  - A framework for sustainable implementation of e-medicine in transitioning
      countries.
AB  - Organizations in developed countries such as the United States of America and
      Canada face difficulties and challenges in technology transfer from one
      organization to another; the complexity of problems easily compounds when such
      transfers are attempted from developed to developing countries due to differing
      socioeconomic and cultural environments. There is a gap in the formation of
      research and education programs to address technology transfer issues that go
      beyond just transferring the technologies to sustaining such transfers for longer
      periods. This study examined telemedicine transfer challenges in three Sub-Sahara
      African countries and developed a framework for sustainable implementation of e
      medicine. Both quantitative and qualitative research methods were used. The study
      findings indicate that e-medicine sustainability in Sub-Saharan Africa is
      affected by institutional factors such as institutional environment and knowledge
      management practices; technical factors such as the technological environment and
      technology transfer project environment; social environmental factors such as
      social environment and donor involvement. These factors were used to model the
      proposed framework. 

PMID- 24454354
TI  - Smartphone Medical Applications for Women's Health: What Is the Evidence-Base and
      Feedback?
AB  - Background. Smartphone medical applications have a major role to play in women's
      health with their roles being very broad, ranging from improving health
      behaviours to undertaking personalised tests. Objective(s). Using Medline, Web of
      Knowledge, and the PRISMA guidelines 15 randomized controlled trials (RCTs) were
      identified, with mobile interventions being tested on 1603 females, in relation
      to key aspects of health. Using a similar systematic approach an iPhone database
      search identified 47 applications (apps) developed to improve women's health.
      Findings. Ten RCTs used text messaging or app interventions to support weight
      loss, with significant improvements being observed in eight studies. For other
      aspects of women's health RCTs are needed to determine possible health benefits.
      iPhone store data analysis identified that a substantial number of women's health
      apps did not have star ratings or feedback comments (68 and 49 per cent, resp.),
      raising concerns about their validity. Conclusion. Peer-review systems,
      supporting statements of evidence, or certification standards would be beneficial
      in maintaining the quality and credibility of future health-focused apps. Patient
      groups should also ideally be involved in the development and testing of mobile
      medical apps. 

PMID- 24454355
TI  - Assistive/Socially assistive robotic platform for therapy and recovery: patient
      perspectives.
AB  - Improving adherence to therapy is a critical component of advancing outcomes and
      reducing the cost of rehabilitation. A robotic platform was previously developed
      to explore how robotics could be applied to the social dimension of
      rehabilitation to improve adherence. This paper aims to report on feedback given
      by end users of the robotic platform as well as the practical applications that
      socially assistive robotics could have in the daily life activities of a patient.
      A group of 10 former and current patients interacted with the developed robotic
      platform during a simulated exercise session before taking an experience-based
      survey. A portion of these participants later provided verbal feedback as part of
      a focus group on the potential utility of such a platform. Identified
      applications included assistance with reaching exercise goals, managing to-do
      lists, and supporting participation in social and recreational activities. The
      study participants expressed that the personality characteristics of the robotic
      system should be adapted to individual preferences and that the assistance
      provided over time should align with the progress of their recovery. The results
      from this study are encouraging and will be useful for further development of
      socially assistive robotics. 

PMID- 24454356
TI  - Phenoxybenzamine in complex regional pain syndrome: potential role and novel
      mechanisms.
AB  - There is a relatively long history of the use of the alpha -adrenergic
      antagonist, phenoxybenzamine, for the treatment of complex regional pain syndrome
      (CRPS). One form of this syndrome, CRPS I, was originally termed reflex
      sympathetic dystrophy (RSD) because of an apparent dysregulation of the
      sympathetic nervous system in the region of an extremity that had been subjected
      to an injury or surgical procedure. The syndrome develops in the absence of any
      apparent continuation of the inciting trauma. Hallmarks of the condition are
      allodynia (pain perceived from a nonpainful stimulus) and hyperalgesia
      (exaggerated pain response to a painful stimulus). In addition to severe,
      unremitting burning pain, the affected limb is typically warm and edematous in
      the early weeks after trauma but then progresses to a primarily cold, dry limb in
      later weeks and months. The later stages are frequently characterized by changes
      to skin texture and nail deformities, hypertrichosis, muscle atrophy, and bone
      demineralization. Earlier treatments of CRPS syndromes were primarily focused on
      blocking sympathetic outflow to an affected extremity. The use of an alpha 
      adrenergic antagonist such as phenoxybenzamine followed from this perspective.
      However, the current consensus on the etiology of CRPS favors an interpretation
      of the symptomatology as an evidence of decreased sympathetic activity to the
      injured limb and a resulting upregulation of adrenergic sensitivity. The clinical
      use of phenoxybenzamine for the treatment of CRPS is reviewed, and mechanisms of
      action that include potential immunomodulatory/anti-inflammatory effects are
      presented. Also, a recent study identified phenoxybenzamine as a potential
      intervention for pain mediation from its effects on gene expression in human cell
      lines; on this basis, it was tested and found to be capable of reducing pain
      behavior in a classical animal model of chronic pain. 

PMID- 24454357
TI  - Health-related quality of life measures for physically active elderly in
      community exercise programs in catalonia: comparative analysis with sedentary
      people.
AB  - Objective. To evaluate Health-Related Quality of Life (HRQoL), medication used,
      and Stock of Health Capital (SHC) in physically active elderly participants in
      Community Exercise Programs (CEPs) compared to a sedentary group. Methods.
      EuroQol standardized instrument was completed by physically active elderly (n =
      2,185) who participated in CEPs. Common items were compared to HRQoL data of
      1,874 sedentary elderly people, taken from the Catalan Health Survey 2006
      (CHS'06). Visual Analogue Scale (VAS) outcomes and medication used were assessed
      through parametric statistics. Dimensions of health conditions were compared,
      between sedentary people and physically active elderly participants in CEPs. SHC
      results were obtained combining the EuroQol scores and Life Expectancy (LE)
      values. An economic value of ?34,858.70 was assigned to these years of LE.
      Results. Physically active subjects had better HRQoL values (75.36 in males and
      70.71 in females) than CHS'06 sedentary subjects (58.35 in males and 50.59 in
      females). Medication used was different between physically active subjects (1.89
      in males and 2.87 in females) and CHS'06 sedentary subjects (4.34 in males and
      4.21 in females). SHC data for physically active elderly (?465,988.31/QALY in
      males and ?522,550.31/QALY in females) were higher than for CHS'06 sedentary
      subjects (?363,689.33/QALY in males and ?346,615.91/QALY in females). 

PMID- 24454358
TI  - It is always on your mind: experiences and perceptions of falling of older people
      and their carers and the potential of a mobile falls detection device.
AB  - Background. Falls and fear of falling present a major risk to older people as
      both can affect their quality of life and independence. Mobile assistive
      technologies (AT) fall detection devices may maximise the potential for older
      people to live independently for as long as possible within their own homes by
      facilitating early detection of falls. Aims. To explore the experiences and
      perceptions of older people and their carers as to the potential of a mobile
      falls detection AT device. Methods. Nine focus groups with 47 participants
      including both older people with a range of health conditions and their carers.
      Interviews were audio recorded, transcribed verbatim, and thematically analysed.
      Results. Four key themes were identified relating to participants' experiences
      and perceptions of falling and the potential impact of a mobile falls detector:
      cause of falling, falling as everyday vulnerability, the environmental context of
      falling, and regaining confidence and independence by having a mobile falls
      detector. Conclusion. The perceived benefits of a mobile falls detector may
      differ between older people and their carers. The experience of falling has to be
      taken into account when designing mobile assistive technology devices as these
      may influence perceptions of such devices and how older people utilise them. 

PMID- 24454359
TI  - Intraindividual variability in domain-specific cognition and risk of mild
      cognitive impairment and dementia.
AB  - Intraindividual variability among cognitive domains may predict dementia
      independently of interindividual differences in cognition. A multidomain
      cognitive battery was administered to 2305 older adult women (mean age 74 years)
      enrolled in an ancillary study of the Women's Health Initiative. Women were
      evaluated annually for probable dementia and mild cognitive impairment (MCI) for
      an average of 5.3 years using a standardized protocol. Proportional hazards
      regression showed that lower baseline domain-specific cognitive scores
      significantly predicted MCI (N = 74), probable dementia (N = 45), and MCI or
      probable dementia combined (N = 101) and that verbal and figural memory predicted
      each outcome independently of all other cognitive domains. The baseline
      intraindividual standard deviation across test scores (IAV Cognitive Domains)
      significantly predicted probable dementia and this effect was attenuated by
      interindividual differences in verbal episodic memory. Slope increases in IAV
      Cognitive Domains across measurement occasions (IAV Time) explained additional
      risk for MCI and MCI or probable dementia, beyond that accounted for by
      interindividual differences in multiple cognitive measures, but risk for probable
      dementia was attenuated by mean decreases in verbal episodic memory slope. These
      findings demonstrate that within-person variability across cognitive domains both
      at baseline and longitudinally independently accounts for risk of cognitive
      impairment and dementia in support of the predictive utility of within-person
      variability. 

PMID- 24454360
TI  - The principle of stationary action in biophysics: stability in protein folding.
AB  - We conceptualize protein folding as motion in a large dimensional dihedral angle
      space. We use Lagrangian mechanics and introduce an unspecified Lagrangian to
      study the motion. The fact that we have reliable folding leads us to conjecture
      the totality of paths forms caustics that can be recognized by the vanishing of
      the second variation of the action. There are two types of folding processes:
      stable against modest perturbations and unstable. We also conjecture that natural
      selection has picked out stable folds. More importantly, the presence of caustics
      leads naturally to the application of ideas from catastrophe theory and allows us
      to consider the question of stability for the folding process from that
      perspective. Powerful stability theorems from mathematics are then applicable to
      impose more order on the totality of motions. This leads to an immediate
      explanation for both the insensitivity of folding to solution perturbations and
      the fact that folding occurs using very little free energy. The theory of
      folding, based on the above conjectures, can also be used to explain the behavior
      of energy landscapes, the speed of folding similar to transition state theory,
      and the fact that random proteins do not fold. 

PMID- 24454361
TI  - The Aryl-Hydrocarbon Receptor Protein Interaction Network (AHR-PIN) as Identified
      by Tandem Affinity Purification (TAP) and Mass Spectrometry.
AB  - The aryl-hydrocarbon receptor (AHR), a ligand activated PAS superfamily
      transcription factor, mediates most, if not all, of the toxicity induced upon
      exposure to various dioxins, dibenzofurans, and planar polyhalogenated biphenyls.
      While AHR-mediated gene regulation plays a central role in the toxic response to
      dioxin exposure, a comprehensive understanding of AHR biology remains elusive.
      AHR-mediated signaling starts in the cytoplasm, where the receptor can be found
      in a complex with the heat shock protein of 90 kDa (Hsp90) and the immunophilin
      like protein, aryl-hydrocarbon receptor-interacting protein (AIP). The role these
      chaperones and other putative interactors of the AHR play in the toxic response
      is not known. To more comprehensively define the AHR-protein interaction network
      (AHR-PIN) and identify other potential pathways involved in the toxic response, a
      proteomic approach was undertaken. Using tandem affinity purification (TAP) and
      mass spectrometry we have identified several novel protein interactions with the
      AHR. These interactions physically link the AHR to proteins involved in the
      immune and cellular stress responses, gene regulation not mediated directly via
      the traditional AHR:ARNT heterodimer, and mitochondrial function. This new
      insight into the AHR signaling network identifies possible secondary signaling
      pathways involved in xenobiotic-induced toxicity. 

PMID- 24454362
TI  - Influence of Exposure to Benzo[a]pyrene on Mice Testicular Germ Cells during
      Spermatogenesis.
AB  - The objective of this study was to assess the toxicological effect of exposure to
      benzo(a)pyrene, B[a]P, on germ cells during spermatogenesis. Mice were exposed to
      B[a]P at 1, 10, 50, and 100 mg/kg/day for 30 days via oral ingestion. Germ cells,
      including spermatogonia, spermatocytes, pachytene spermatocytes, and round
      spermatids, were recovered from testes of mice exposed to B[a]P, while mature
      spermatozoa were isolated from vas deferens. Reproductive organs were collected
      and weighed. Apoptotic response of germ cells and mature spermatozoa were
      qualified using the terminal deoxynucleotidyl transferase mediated deoxy-UTP nick
      end labeling (TUNEL) assay. B[a]P exposure at <=10 mg/kg/day for 30 days did not
      significantly alter concentrations of germ cells and mature spermatozoa and
      apoptotic response in germ cells and mature spermatozoa. Exposure to B[a]P at 50
      and 100 mg/kg/day induced testicular atrophy and yielded a significant reduction
      in the concentrations of spermatogonia, spermatocytes, pachytene spermatocytes,
      and round spermatid cells as compared with the control. Also, mature spermatozoa
      experienced decreased concentrations and viability. B[a]P-exposed mice
      experienced a significant increase in apoptotic germ cells as compared to the
      control mice. However, the mice dose concentrations were not relevant for
      comparison to human exposure. 

PMID- 24454363
TI  - Prenatal and postnatal polycyclic aromatic hydrocarbon exposure, airway
      hyperreactivity, and Beta-2 adrenergic receptor function in sensitized mouse
      offspring.
AB  - Despite data associating exposure to traffic-related polycyclic aromatic
      hydrocarbons (PAH) in asthma, mechanistic support has been limited. We
      hypothesized that both prenatal and early postnatal exposure to PAH would
      increase airway hyperreactivity (AHR) and that the resulting AHR may be
      insensitive to treatment with a beta 2AR agonist drug, procaterol. Further, we
      hypothesized that these exposures would be associated with altered beta 2AR gene
      expression and DNA methylation in mouse lungs. Mice were exposed prenatally or
      postnatally to a nebulized PAH mixture versus negative control aerosol 5 days a
      week. Double knockout beta 2AR mice were exposed postnatally only. Prenatal
      exposure to PAH was associated with reduced beta 2AR gene expression among
      nonsensitized mice offspring, but not increases in DNA methylation or AHR.
      Postnatal exposure to PAH was borderline associated with increased AHR among
      sensitized wildtype, but not knockout mice. In the first study that delivers PAH
      aerosols to mice in a relatively physiological manner, small effects on AHR and
      beta 2AR gene expression, but not beta 2AR agonist drug activity, were observed.
      If confirmed, the results may suggest that exposure to PAH, common ambient urban
      pollutants, affects beta 2AR function, although the impact on the efficacy of
      beta 2AR agonist drugs used in treating asthma remains uncertain. 

PMID- 24454364
TI  - Does Regular Exercise without Weight Loss Reduce Insulin Resistance in Children
      and Adolescents?
AB  - Despite considerable efforts to tackle childhood obesity, it is recognized as one
      of the biggest health problems globally. Childhood obesity is a leading cause of
      many comorbid conditions such as metabolic syndrome and insulin resistance as
      well as type 2 diabetes. A strong body of evidence suggests that regular exercise
      without calorie restriction or weight loss is associated with reduced insulin
      resistance as well as improved insulin sensitivity in overweight and obese
      adults. However, despite the well-known benefits associated with regular exercise
      alone, the independent role of exercise training without calorie restriction on
      insulin resistance is still uncertain in youth. Some studies observed that both
      the aerobic and resistance type of exercise training without calorie restriction
      resulted in meaningful changes in insulin sensitivity, suggesting that exercise
      alone is an effective therapeutic strategy for reducing insulin resistance in
      overweight and obese youth. However, only few studies are available on the
      optimal dose of exercise training without calorie restriction or preferred
      exercise modality for reducing insulin resistance, which warrants further
      investigations in the pediatric population. 

PMID- 24454365
TI  - Risk Factors for Thyroid Dysfunction among Type 2 Diabetic Patients in a Highly
      Diabetes Mellitus Prevalent Society.
AB  - Diabetes and thyroid dysfunction found to exist simultaneously. In this regard,
      the present study looked into the prevalence of different forms of thyroid
      dysfunction and their risk factors among Type 2 diabetic Saudi patients.
      Methodology. A cross-sectional retrospective randomized hospital-based study of
      411 Type 2 diabetic Saudi patients of >25 years of age was conducted to test the
      prevalence of different types of thyroid dysfunction and their risk factors.
      Results. The prevalence of different types of thyroid dysfunction is 28.5%, of
      which 25.3% had hypothyroidism, where 15.3%, 9.5%, and 0.5% are clinical,
      subclinical, and overt hypothyroidism, respectively. The prevalence of
      hyperthyroidism is 3.2%, of which subclinical cases accounted for 2.7% and overt
      hyperthyroidism accounted for 0.5%. Risk factors for thyroid dysfunction among
      Saudi Type 2 diabetic patients are family history of thyroid disease, female
      gender, and duration of diabetes of >10 years, while the risk was not significant
      in patients with history of goiter and patients aged >60 years. Smoking and
      parity show a nonsignificant reduced risk. Conclusion. Thyroid dysfunction is
      highly prevalent among Saudi Type 2 diabetic patients, and the most significant
      risk factors are family history of thyroid disease, female gender, and >10 years
      duration of diabetes. 

PMID- 24454367
TI  - Impaired Growth during Childhood in Patients with Primary Ciliary Dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) leads to recurrent/chronic respiratory
      infections, resulting in chronic inflammation and potentially in chronic
      pulmonary disease with bronchiectasis. We analyzed longitudinal data on body
      length/height and body mass index (BMI) for 29 children and young adults with PCD
      aging 1.5-24 years (median, 14.5) who had been diagnosed at the age of 0.5-17
      years (median, 8). Of these, 10 carried pathogenic mutations in either DNAH5 or
      DNAI1. In children with PCD, body length/height progressively decreased from
      +0.40 +/- 0.24 SDS (the 1st birthday), +0.16 +/- 0.23 SDS (3 years old), and 
      0.13 +/- 0.21 SDS (5 years old) to -0.54 +/- 0.19 SDS (7 years old; P = 0.01
      versus 0), -0.67 +/- 0.21 SDS (9 years old; P = 0.005 versus 0), -0.52 +/- 0.24
      SDS (11 years old; P = 0.04 versus 0), and -0.53 +/- 0.23 SDS (13 years old; P =
      0.03 versus 0). These results reflect low growth rates during the childhood
      growth period. Thereafter, heights stabilized up to the age of 17 years. The
      growth deterioration was not dependent on sex or disease severity but was more
      pronounced in DNAH5 or DNAI1 mutation carriers. BMI did not differ from
      population standards, which suggests that nutritional deficits are not the cause
      of growth delay. We conclude that PCD leads to chronic deprivation with
      significant growth deterioration during childhood. 

PMID- 24454366
TI  - Severely obese adolescents and adults exhibit a different association of
      circulating levels of adipokines and leukocyte expression of the related
      receptors with insulin resistance.
AB  - Obese adults frequently exhibit a low-grade inflammation and insulin resistance,
      which have been hypothesized to be established early in childhood. Aim of this
      study was to evaluate the age-dependent relationships between inflammatory state
      and insulin resistance in obese adolescents and adults. Clinical and metabolic
      parameters, circulating adipokines (TNF- alpha , adiponectin, and leptin),
      ghrelin, their leukocyte receptors (TNFR1, ADIPOR2, OBRL and GHSR1a), and acute
      phase reactants (CRP and white blood cells) were assessed in lean and obese
      adolescents compared with the adult counterparts. Only obese adults had higher
      HOMA-IR, insulin, and triglycerides compared to the lean group. An inflammatory
      state was present in obese adolescents and adults, as demonstrated by the higher
      values of CRP and neutrophils. There were no group differences in circulating
      levels of TNF- alpha and leukocyte expression of TNFR1. Adiponectin
      concentrations and leukocyte expression of ADIPOR2 were higher in the lean groups
      than in the corresponding obese counterparts. For leptin and leukocyte expression
      of OBRL, the results were opposed. Circulating levels of ghrelin were higher in
      lean adolescents and adults than the related lean groups, while there was a
      higher leukocyte expression of GHSR1a in (only) lean adults than obese adults.
      When the analysis was performed in (lean or obese) adults, TNF- alpha ,
      neutrophils, leptin, and GHSR1a were predictors of HOMA-IR. None of the
      considered independent variables accounted for the degree of insulin resistance
      in the adolescent group. In conclusion, a dissociation between the low-grade
      inflammation and insulin resistance is supposed to exist in the early phases of
      obesity. 

PMID- 24454368
TI  - Anti-mullerian hormone: usefulness in clinical practice.

PMID- 24454369
TI  - Androgen Receptor Gene CAG Repeat Polymorphism Regulates the Metabolic Effects of
      Testosterone Replacement Therapy in Male Postsurgical Hypogonadotropic
      Hypogonadism.
AB  - Aim. To evaluate the independent role of androgen receptor (AR) gene CAG repeat
      polymorphism on metabolic effects of testosterone replacement therapy (TRT) in
      male postsurgical hypogonadotropic hypogonadism, a condition frequently
      associated with hypopituitarism and in which the TRT-related metabolic effects
      are combined with those deriving from concomitant administration of metabolically
      active pituitary-function replacement therapies. Methods. 15 men affected by
      postsurgical hypogonadotropic hypogonadism were evaluated before and after TRT.
      Cardiovascular risk factors (CVRFs), pituitary-dependent hormones, and AR gene
      CAG repeat polymorphism were considered. Results. Testosterone, insulin-like
      growth factor 1 (IGF-1), and estradiol were the only hormones, which varied
      significantly between the two phases. All CVRFs significantly improved after TRT.
      The number of CAG triplets was positively and significantly correlated with all
      the variations (Delta-) of CVRFs (except for a significant negative correlation
      with Delta-high-density lipoprotein); the opposite occurred between the latter
      and Delta-testosterone. No correlation between Delta-IGF-1 or estradiol and Delta
      CVRFs was found. At multiple linear regression, after correction for Delta
      testosterone, nearly all the associations between the number of CAG triplets and
      Delta-CVRFs were confirmed. Conclusions. In male postsurgical hypogonadotropic
      hypogonadism, shorter AR gene CAG tract length seems to yield greater metabolic
      improvement after TRT, independently of the effects of concomitant pituitary
      function replacement therapies. 

PMID- 24454370
TI  - Comparison of two creatinine-based equations for predicting decline in renal
      function in type 2 diabetic patients with nephropathy in a korean population.
AB  - Aim. To compare two creatinine-based estimated glomerular filtration rate (eGFR)
      equations, the chronic kidney disease epidemiology collaboration (CKD-EPI) and
      the modification of diet in renal disease (MDRD), for predicting the risk of CKD
      progression in type 2 diabetic patients with nephropathy. Methods. A total of 707
      type 2 diabetic patients with 24 hr urinary albumin excretion of more than 30
      mg/day were retrospectively recruited and traced until doubling of baseline serum
      creatinine (SCr) levels was noted. Results. During the follow-up period (median,
      2.4 years), the CKD-EPI equation reclassified 10.9% of all MDRD-estimated
      subjects: 9.1% to an earlier stage of CKD and 1.8% to a later stage of CKD.
      Overall, the prevalence of CKD (eGFR < 60 mL/min/1.73 m(2)) was lowered from 54%
      to 51.6% by applying the CKD-EPI equation. On Cox-regression analysis, both
      equations exhibited significant associations with an increased risk for doubling
      of SCr. However, only the CKD-EPI equation maintained a significant hazard ratio
      for doubling of SCr in earlier-stage CKD (eGFR >= 45 mL/min/1.73 m(2)), when
      compared to stage 1 CKD (eGFR >= 90 mL/min/1.73 m(2)). Conclusion. In regard to
      CKD progression, these results suggest that the CKD-EPI equation might more
      accurately stratify earlier-stage CKD among type 2 diabetic patients with
      nephropathy than the MDRD study equation. 

PMID- 24454371
TI  - Impaired fasting glucose and diabetes as predictors for radial artery
      calcification in end stage renal disease patients.
AB  - Objective. The objective of the study was to assess the relationship between
      selected clinical and biochemical parameters of end stage renal disease (ESRD)
      patients and arterial calcification. Materials and Methods. The study comprised
      59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis).
      The examined parameters included common carotid artery intima-media thickness
      (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG),
      dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric
      dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and
      osteocalcin (OC) were also measured. Fragments of radial artery obtained during
      creation of hemodialysis access were stained for calcifications using von Kossa
      method and alizarin red. Results. Calcification of radial artery was
      significantly associated with higher prevalence of IFG and diabetes (P = 0.0004)
      and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA
      concentrations (P = 0.022). Fasting glucose >5.6 mmol/l (IFG and diabetes)
      significantly predicted vascular calcification in multiple logistic regression.
      The calcification was also associated with higher CCA-IMT (P = 0.006) and
      mortality (P = 0.004; OR for death 5.39 [1.20-24.1] after adjustment for dialysis
      status and age). Conclusion. Combination of renal insufficiency and hyperglycemic
      conditions exerts a synergistic effect on vascular calcification and increases
      the risk of death. 

PMID- 24454372
TI  - Serum p53 Antibody Is Not Associated with p53 Immunoreactivity in Patients with
      Pancreatobiliary Cancers.
AB  - Background. Recent diagnostic imaging tests contribute to improving the diagnosis
      of pancreatobiliary cancers. However, it is not practical to perform these tests
      for all patients as screening. Thus, less-invasive and simple screening tests are
      still required. A method to detect the IgG antibody induced in serum against the
      p53 protein accumulating due to p53 gene mutation, as a biomarker, was developed
      around 1990. Method. 35 patients with pancreatic cancer, 12 patients with biliary
      tract cancer, and 31 patients with benign pancreatobiliary diseases were entered
      into this study. Measurement of serum anti-p53 antibody was conducted in all
      patients. In addition, the rate of p53 protein overexpression was examined in
      those cases that could be examined pathologically. Result. Among all patients in
      the pancreatic cancer and biliary tract cancer groups, there was no patient with
      serum anti-p53 antibody positive value that exceeded the standard value. The rate
      of p53 protein overexpression was 48.0% in the patients with pancreatobiliary
      cancers and 0% in the benign pancreatobiliary diseases group. Conclusion. Serum
      anti-p53 antibody measurement does not contribute to the diagnosis of
      pancreatobiliary cancers. Instead, traditional p53 immunostaining still appears
      to be valuable in combination with standard procedures. 

PMID- 24454373
TI  - The Impact of Adjustment for Socioeconomic Status on Comparisons of Cancer
      Incidence between Two European Countries.
AB  - Background. Cancer incidence rates vary considerably between countries and by
      socioeconomic status (SES). We investigate the impact of SES upon the relative
      cancer risk in two neighbouring countries. Methods. Data on 229,824 cases for 16
      cancers diagnosed in 1995-2007 were extracted from the cancer registries in
      Northern Ireland (NI) and Republic of Ireland (RoI). Cancers in the two countries
      were compared using incidence rate ratios (IRRs) adjusted for age and age plus
      area-based SES. Results. Adjusting for SES in addition to age had a considerable
      impact on NI/RoI comparisons for cancers strongly related to SES. Before SES
      adjustment, lung cancer incidence rates were 11% higher for males and 7% higher
      for females in NI, while after adjustment, the IRR was not statistically
      significant. Cervical cancer rates were lower in NI than in RoI after adjustment
      for age (IRR: 0.90 (0.84-0.97)), with this difference increasing after adjustment
      for SES (IRR: 0.85 (0.79-0.92)). For cancers with a weak or nonexistent
      relationship to SES, adjustment for SES made little difference to the IRR.
      Conclusion. Socioeconomic factors explain some international variations but also
      obscure other crucial differences; thus, adjustment for these factors should not
      become part of international comparisons. 

PMID- 24454374
TI  - Cancer Mortality among Asians and Pacific Islanders in New York City, 2001-2010.
AB  - Asians and Pacific Islanders' (APIs) leading cause of death is cancer. We
      compared APIs' age-adjusted cancer mortality rates to other racial/ethnic groups
      and by API subgroup (i.e., Chinese, Koreans, Asian Indians, and Filipinos) using
      New York City (NYC) Mortality data and Census Bureau population estimates for
      2001-2010. While other racial/ethnic groups' overall cancer mortality rates
      declined in NYC during the last decade, APIs remained stable. APIs overall had
      the lowest mortality rates for more common cancer types (i.e., lung, colorectal,
      breast, and prostate), but the highest mortality rates for certain less common
      cancers (i.e., nasopharyngeal, stomach, and liver). Chinese New Yorkers' lung
      cancer death rates were very high compared to other APIs and comparable to non
      Hispanic whites (47.1/100,000 versus 49.5/100,000, resp.). Chinese men had much
      higher nasopharyngeal cancer mortality rates (4.5/100,000 versus 0.3/100,000 for
      non-Hispanic whites). Korean men had the highest liver and stomach cancer
      mortality rates (25.3/100,000 and 27.7/100,000, resp., versus 7.9/100,000 and
      6.0/100,000 for non-Hispanic whites). Analysis of cancer rates by API subgroup
      provides the detailed information needed to plan cancer prevention efforts. These
      findings warrant consideration of targeted cancer mortality prevention efforts
      for affected subgroups, including hepatitis vaccination, screening, and
      treatment; smoking cessation; and cancer screening. 

PMID- 24454375
TI  - Impact of periodontal diseases on health-related quality of life of users of the
      brazilian unified health system.
AB  - Objective. This study assessed the impact of periodontal diseases on health
      related quality of life of adult users of the Brazilian Unified Health System.
      Study Design. A cross-sectional study was conducted on an outpatient basis. The
      sample included 151 adults treated in the Periodontics section at Dental
      Specialty Centres of Juiz de Fora (Minas Gerais, Brazil). The Oral Health Impact
      Profile (OHIP-14) measured the impact of periodontal disease on quality of life.
      Participants were interviewed to obtain self-perception of general and oral
      health and socioeconomic data, and dental records were consulted to obtain
      periodontal status data. The values of central tendency of the OHIP-14 were
      compared with socioeconomic, demographic, and self-reported health predictors
      using nonparametric tests. The final analysis was performed using multiple linear
      regressions. Results. The results showed that psychological discomfort and
      physical disability exhibited a negative impact. The following variables can
      explain approximately 27% of the impact of oral health conditions on health
      related quality of life in this group: periodontal disease, self-perceived oral
      health, and the need to use or replace dental prosthesis. Conclusion. The need
      for prosthetic rehabilitation and worse periodontal status are associated with
      health-related quality of life, which can be predicted by the self-perception of
      health. 

PMID- 24454376
TI  - Blends of thermoplastic polyurethane and polydimethylsiloxane rubber: assessment
      of biocompatibility and suture holding strength of membranes.
AB  - In the present investigation, a compatibilized blend of thermoplastic
      polyurethane (TPU) and polydimethylsiloxane (PDMS) is prepared by using copolymer
      of ethylene and methyl acrylate (EMA) as a reactive compatibilizer. Detailed in
      vitro biocompatibility studies were carried out for this compatibilized blend and
      the material was found noncytotoxic towards L929 mouse fibroblast subcutaneous
      connective tissue cell line. Microporosity was created on the surface of
      membranes prepared from the blend material by adopting the crazing mechanism.
      Cell proliferation and growth studies on the membranes surface showed that the
      microporous surface favoured ingrowth of the cells compared with a nonmicroporous
      surface. Suture holding strength studies indicate that the microporous membranes
      have enough strength to withstand the cutting and tearing forces through the
      suture hole. This blend material could be evaluated further to find its
      suitability in various implant applications. 

PMID- 24454377
TI  - Bone substitutes for peri-implant defects of postextraction implants.
AB  - Placement of implants in fresh sockets is an alternative to try to reduce
      physiological resorption of alveolar ridge after tooth extraction. This surgery
      can be used to preserve the bone architecture and also accelerate the restorative
      procedure. However, the diastasis observed between bone and implant may influence
      osseointegration. So, autogenous bone graft and/or biomaterials have been used to
      fill this gap. Considering the importance of bone repair for treatment with
      implants placed immediately after tooth extraction, this study aimed to present a
      literature review about biomaterials surrounding immediate dental implants. The
      search included 56 articles published from 1969 to 2012. The results were based
      on data analysis and discussion. It was observed that implant fixation
      immediately after extraction is a reliable alternative to reduce the treatment
      length of prosthetic restoration. In general, the biomaterial should be used to
      increase bone/implant contact and enhance osseointegration. 

PMID- 24454378
TI  - Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy.
AB  - Prion diseases are linked to the accumulation of a misfolded isoform (PrP(Sc)) of
      prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints
      and sites of the accumulation of PrP(Sc). We questioned whether lysosomes
      participate in the early quality control of newly generated misfolded PrP. We
      found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered
      to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed
      early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker
      labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an
      elevation in several markers of the autophagy-lysosomal pathway, and it
      extensively colocalized with the autophagosome-specific marker, LC3B. In
      autophagy deficient (ATG5(-/-)) mouse embryonic fibroblasts, or in normal cells
      treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes
      was reduced to a similar extent. Additionally, 3-MA selectively impaired the
      degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant
      PrP, whereas the induction of autophagy by rapamycin reduced it. These findings
      suggest that autophagy might function as a quality control mechanism to limit the
      accumulation of misfolded PrP that normally leads to the generation of PrP(Sc). 

PMID- 24454380
TI  - Characteristics and Results of the Treatment of Multiple Myeloma in the Subject
      under the Age of 65 at the University Hospital of Yopougon in Abidjan, Cote
      d'Ivoire.
AB  - We retrospectively studied 30 cases of multiple myeloma in patients under the age
      of 65, diagnosed from 1991 to 2005 in the clinical hematology department of the
      University Hospital of Yopougon that is a hospital incidence of 2.9 cases/year.
      The age of patients ranged from 34 to 64 years, with a mean age of 49 years and a
      sex ratio of 1.73. The professional activity was variable with 3% of
      radiographers and 10% of farmers. Clinically, the dominant sign was bone pain in
      83% of cases. Myeloma was secretory in 93% of cases. It was Ig G-type in 86%,
      kappa-type in 66% of cases. 86% of patients were anemic, 20% had creatinine >20
      mg/L, and 10% had serum calcium >120 mg/L. Geodes were found in 80% of cases. 53%
      were at stage III of DURIE and SALMON. Complications were infectious (33%), renal
      (20%), and hemorrhagic (7%). Chemotherapy regimens were VAD (10%), VMCP (30%),
      and VMCP/VBAP (60%) with 47% of partial responses, 33% of stable disease, and 7%
      of very good quality partial responses. The outcome developed towards death in
      37% and causes of death were renal in 46% of cases. The median survival was only
      5.1 months. 

PMID- 24454382
TI  - Seasonal levels of the Vibrio predator bacteriovorax in atlantic, pacific, and
      gulf coast seawater.
AB  - Bacteriovorax were quantified in US Atlantic, Gulf, and Pacific seawater to
      determine baseline levels of these predatory bacteria and possible seasonal
      fluctuations in levels. Surface seawater was analyzed monthly for 1 year from
      Kailua-Kona, Hawaii; the Gulf Coast of Alabama; and four sites along the Delaware
      Bay. Screening for Bacteriovorax was performed on lawns of V. parahaemolyticus
      host cells. Direct testing of 7.5 mL portions of seawater from the Atlantic,
      Pacific, and Gulf coasts gave mean annual counts <=12.2 PFU. Spikes in counts
      were observed at 3 out of 4 sites along the Delaware Bay 1 week after Hurricane
      Sandy. A comparison of summer versus winter counts showed significantly more
      Bacteriovorax (P <= 0.0001) in the Delaware Bay during the summer and
      significantly more (P <= 0.0001) in the Gulf during the winter, but no
      significant seasonal differences (P > 0.05) for Hawaiian seawater. Bacteriovorax
      counts only correlated with seawater salinity and temperature at one Delaware
      site (r = 0.79 and r = 0.65, resp.). There was a relatively strong negative
      correlation between temperature and Bacteriovorax levels (r = -0.585) for Gulf
      seawater. Selected isolates were sequenced and identified by phylogenetic
      analysis as Bacteriovorax clusters IX, X, XI, and XII. 

PMID- 24454383
TI  - Formulation and Statistical Optimization of Culture Medium for Improved
      Production of Antimicrobial Compound by Streptomyces sp. JAJ06.
AB  - Streptomyces sp. JAJ06 is a seawater-dependent antibiotic producer, previously
      isolated and characterised from an Indian coastal solar saltern. This paper
      reports replacement of seawater with a defined salt formulation in production
      medium and subsequent statistical media optimization to ensure consistent as well
      as improved antibiotic production by Streptomyces sp. JAJ06. This strain was
      observed to be proficient to produce antibiotic compound with incorporation of
      chemically defined sodium-chloride-based salt formulation instead of seawater
      into the production medium. Plackett-Burman design experiment was applied, and
      three media constituents, starch, KBr, and CaCO3, were recognised to have
      significant effect on the antibiotic production of Streptomyces JAJ06 at their
      individual levels. Subsequently, Response surface methodology with Box-Behnken
      design was employed to optimize these influencing medium constituents for the
      improved antibiotic production of Streptomyces sp. JAJ06. A total of 17
      experiments were conducted towards the construction of a quadratic model and a
      second-order polynomial equation. Optimum levels of medium constituents were
      obtained by analysis of the model and numerical optimization method. When the
      strain JAJ06 was cultivated in the optimized medium, the antibiotic activity was
      increased to 173.3 U/mL, 26.8% increase as compared to the original (136.7 U/mL).
      This study found a useful way to cultivate Streptomyces sp. JAJ06 for enhanced
      production of antibiotic compound. 

PMID- 24454381
TI  - MicroRNAs as Haematopoiesis Regulators.
AB  - The production of different types of blood cells including their formation,
      development, and differentiation is collectively known as haematopoiesis. Blood
      cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T
      cells), and myeloid (granulocytes, megakaryocytes, and macrophages).
      Haematopoiesis is a complex process regulated by several mechanisms including
      microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a
      number of genes involved in commitment and differentiation of hematopoietic stem
      cells. Evidence shows that miRNAs play an important role in haematopoiesis; for
      example, myeloid and erythroid differentiation is blocked by the overexpression
      of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR
      150 plays a role in B and T cell differentiation. miR-146 and miR-10a are
      downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in
      hematological malignancies including chronic myelogenous leukemia, chronic
      lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we
      have focused on discussing the role of miRNA in haematopoiesis. 

PMID- 24454379
TI  - Prion protein misfolding, strains, and neurotoxicity: an update from studies on
      Mammalian prions.
AB  - Prion diseases, also known as transmissible spongiform encephalopathies (TSEs),
      are a group of fatal neurodegenerative disorders affecting humans and other
      mammalian species. The central event in TSE pathogenesis is the conformational
      conversion of the cellular prion protein, PrP(C), into the aggregate, beta -sheet
      rich, amyloidogenic form, PrP(Sc). Increasing evidence indicates that distinct
      PrP(Sc) conformers, forming distinct ordered aggregates, can encipher the
      phenotypic TSE variants related to prion strains. Prion strains are TSE isolates
      that, after inoculation into syngenic hosts, cause disease with distinct
      characteristics, such as incubation period, pattern of PrP(Sc) distribution, and
      regional severity of histopathological changes in the brain. In analogy with
      other amyloid forming proteins, PrP(Sc) toxicity is thought to derive from the
      existence of various intermediate structures prior to the amyloid fiber formation
      and/or their specific interaction with membranes. The latter appears particularly
      relevant for the pathogenesis of TSEs associated with GPI-anchored PrP(Sc), which
      involves major cellular membrane distortions in neurons. In this review, we
      update the current knowledge on the molecular mechanisms underlying three
      fundamental aspects of the basic biology of prions such as the putative mechanism
      of prion protein conversion to the pathogenic form PrP(Sc) and its propagation,
      the molecular basis of prion strains, and the mechanism of induced neurotoxicity
      by PrP(Sc) aggregates. 

PMID- 24454384
TI  - Evidence of Bacterial Biofilms among Infected and Hypertrophied Tonsils in
      Correlation with the Microbiology, Histopathology, and Clinical Symptoms of
      Tonsillar Diseases.
AB  - Diseases of the tonsils are becoming more resistant to antibiotics due to the
      persistence of bacteria through the formation of biofilms. Therefore,
      understanding the microbiology and pathophysiology of such diseases represent an
      important step in the management of biofilm-related infections. We have isolated
      the microorganisms, evaluated their antimicrobial susceptibility, and detected
      the presence of bacterial biofilms in tonsillar specimens in correlation with the
      clinical manifestations of tonsillar diseases. Therefore, a total of 140 palatine
      tonsils were collected from 70 patients undergoing tonsillectomy at University
      Malaya Medical Centre. The most recovered isolate was Staphylococcus aureus
      (39.65%) followed by Haemophilus influenzae (18.53%). There was high
      susceptibility against all selected antibiotics except for cotrimoxazole.
      Bacterial biofilms were detected in 60% of patients and a significant percentage
      of patients demonstrated infection manifestation rather than obstruction. In
      addition, an association between clinical symptoms like snore, apnea, nasal
      obstruction, and tonsillar hypertrophy was found to be related to the
      microbiology of tonsils particularly to the presence of biofilms. In conclusion,
      evidence of biofilms in tonsils in correlation with the demonstrated clinical
      symptoms explains the recalcitrant nature of tonsillar diseases and highlights
      the importance of biofilm's early detection and prevention towards better
      therapeutic management of biofilm-related infections. 

PMID- 24454385
TI  - A simple step test to estimate cardio-respiratory fitness levels of rheumatoid
      arthritis patients in a clinical setting.
AB  - Purpose. Exercise tests represent an important clinical tool to evaluate cardio
      respiratory fitness and to predict future adverse cardiovascular events. However,
      use of such tests in patients with rheumatoid arthritis (RA) is relatively
      uncommon despite well-established evidence that low exercise capacity and high
      CVD mortality are features of this disease. Therefore, this study examined the
      validity and reliability of a sub-maximal step test for use in RA patients.
      Methods. Thirty patients (24 females) (mean +/- SD age 53 +/- 10 years) performed
      a sub-maximal step test on two occasions to estimate the criterion measure of
      cardio-respiratory fitness ([Formula: see text]). A further maximal cycling test
      provided a direct fitness measurement ([Formula: see text]). Pearson correlation
      coefficient, intraclass correlation coefficient (ICC), Bland and Altman plots,
      and 95% limits of agreement (LOA) were used to determine the validity and
      reliability of the sub-maximal test. Results. Estimated [Formula: see text]
      correlated well with directly measured [Formula: see text] (r = 0.79, LoA +/-5.7
      mL.kg(-1) .min(-1)). Test-retest reproducibility for estimated [Formula: see
      text] was excellent (ICC = 0.97, LoA +/-2.2 mL.kg(-1) .min(-1)). Conclusion. The
      sub-maximal step test studied here represents a valid and reproducible method to
      estimate cardio-respiratory fitness in RA patients. This test may be useful for
      the assessment and management of CVD risk in a clinical setting. 

PMID- 24454387
TI  - Discrepancies between Antimullerian Hormone and Follicle Stimulating Hormone in
      Assisted Reproduction.
AB  - Data from 107 women undergoing their first IVF/ICSI were analyzed. Relationships
      between antimullerian hormone (AMH) and follicle stimulating hormone (FSH) were
      analyzed after dividing patients into four groups according to AMH/FSH levels.
      Concordance was noted in 57% of women (both AMH/FSH either normal or abnormal)
      while 43%of women had discordant values (AMH/FSH one hormone normal and the other
      abnormal). Group 1 (AMH and FSH in normal range) and group 2 (normal AMH and high
      FSH) were younger compared to group 3 (low AMH and normal FSH) and group 4 (both
      AMH/FSH abnormal). Group 1 showing the best oocyte yield was compared to the
      remaining three groups. Groups 3 and 4 required higher dose of gonadotrophins for
      controlled ovarian hyperstimulation showing their low ovarian reserve. There was
      no difference in cycle cancellation, clinical pregnancy, and live birth/ongoing
      pregnancy rate in all groups. These tests are useful to predict ovarian response
      but whether AMH is a substantially better predictor is not yet established. 

PMID- 24454386
TI  - HIV and Menopause: A Systematic Review of the Effects of HIV Infection on Age at
      Menopause and the Effects of Menopause on Response to Antiretroviral Therapy.
AB  - More than half of persons living with HIV infection in the United States (U.S.)
      will be >=50 years of age by 2020, including postmenopausal women. We conducted a
      systematic literature review about the effects of (1) HIV infection on age at
      menopause and (2) menopause on antiretroviral therapy (ART) response, in order to
      inform optimal treatment strategies for menopausal women living with HIV
      infection. We used the Ovid Medline database from 1980 to 2012. We included
      studies that focused on HIV-infected persons, included postmenopausal women, and
      reported outcome data for either age at menopause or response to ART across
      menopause. We identified six original research articles for age at menopause and
      five for response to ART across menopause. Our review revealed that current data
      were conflicting and inconclusive; more rigorous studies are needed.
      Disentangling the effects of menopause requires well-designed studies with
      adequate numbers of HIV-infected and HIV-uninfected women, especially
      disproportionately affected women of color. Future studies should follow women
      from premenopause through menopause, use both surveys and laboratory measurements
      for menopause diagnoses, and control for confounders related to normal aging
      processes, in order to inform optimal clinical management for menopausal women
      living with HIV. 

PMID- 24454388
TI  - A Review of Comparison of Complications of Vaginal Hysterectomy with and without
      Concomitant Surgery for SUI: A 5 Years' Experience at a Tertiary Care Hospital of
      Pakistan.
AB  - Objective. The study was performed to review the complications of surgery for POP
      with or without surgery for SUI. This included the need for second procedure two
      years after the primary surgery. Study Design. We conducted a retrospective cross
      sectional comparative study at the Aga Khan University, Karachi, Pakistan.
      International Classification of Diseases, 9th revision, Clinical Modification
      (ICD-9-CM) was used to identify women who underwent vaginal hysterectomy with
      anterior/posterior repair alone and those with concomitant tension-free vaginal
      tape surgery for urodynamic stress incontinence. Results. The 28 cases of
      VH/repair combined with TVT were compared for complications with 430 cases of VH
      with repair alone. The basic characteristics like age, BMI, and degree of
      prolapse showed no statistical difference among two groups. The main
      comorbidities in both groups were hypertension, diabetes, and bronchial asthma.
      We observed no significant differences in intraoperative and postoperative
      complications except for cuff abscess, need for medical intervention, and
      readmission following discharge from hospital, which were higher in cases with
      vaginal hysterectomy with concomitant TVT. Conclusions. Vaginal hysterectomy is
      an efficient treatment for uterovaginal prolapse with a swift recovery, short
      length of hospital stay, and rare serious complications. The addition of surgery
      for USI does not appear to increase the morbidity. 

PMID- 24454389
TI  - An elderly lady with Fever of unknown etiology and severe pulmonary hypertension:
      intravascular lymphoma-an elusive diagnosis.
AB  - Pulmonary hypertension (PH) associated with malignancy, especially
      adenocarcinoma, is a well-known entity and is included in group V of the WHO
      classification. Intravascular lymphoma is a rare type of diffuse large B cell
      lymphoma, characterized by selective intravascular growth of malignant
      lymphocytes, aggressive behavior, and often a fatal course. Most of the time,
      diagnosis is postmortem due to the rarity and the protean manifestations of the
      disease. We present a rare case of an elderly patient presenting with severe
      pulmonary hypertension, fever of unknown etiology (FUO), and lymphadenopathy.
      Extensive evaluation searching for the etiology of her FUO and PH was
      noncontributory. The diagnosis of intravascular lymphoma was finally reached by
      the performance of a random abdominal fat pad biopsy and the patient was started
      on immunochemotherapy. She continues the follow up after 6 cycles of R-CHOP with
      no further febrile episodes and steady improvement in exercise tolerance. 

PMID- 24454390
TI  - Primary percutaneous coronary intervention in a patient with haemophilia a.
AB  - Haemophilia A is a rare genetic condition leading to coagulation factor VIII
      deficiency and thus predisposing to bleeding diathesis. Due to advances in
      treatment, life expectancy of haemophilia A sufferers is increasing, and the
      incidence and prevalence of coronary artery disease are rising. There have been
      many reported cases of acute myocardial infarction in such patients, who
      subsequently undergo elective percutaneous coronary intervention. We present the
      case of a 55-year-old gentleman presenting with an acute anterior full-thickness
      myocardial infarction who required emergency primary percutaneous coronary
      intervention. 

PMID- 24454391
TI  - Anomalous Right Coronary Artery from Left Main Coronary Artery and Subsequent
      Coursing between Aorta and Pulmonary Trunk.
AB  - Anomalous origin of left main coronary artery or right coronary artery from the
      aorta with subsequent coursing between the aorta and pulmonary trunk is rare and
      can be sometimes life threatening. After hypertrophic cardiomyopathy, coronary
      artery anomalies are the second most common cause of sudden cardiac deaths among
      young athletes. This is a case presentation of an anomalous origin of right
      coronary artery from left main coronary artery coursing between the pulmonary
      trunk and aorta. Patient presented with STEMI and had coronary bypass surgery. 

PMID- 24454392
TI  - Schizencephaly and psychosis: a rare association.
AB  - Schizencephaly is a rare malformation of the central nervous system defined as a
      gray matter-lined cleft filled with cerebrospinal fluid that extends from the
      pial surface to the ventricle. Few cases of association with psychosis were
      reported in the scientific literature. We present a case of a 46-year-old woman,
      admitted into a psychiatric hospital with crises of psychomotor agitation,
      disorganized and erotized behavior, persecutory and self-reference delusions, and
      auditory and visual hallucinations. She also reported seizures since her
      childhood. A head CT scan revealed a large subarachnoid space communication with
      the adjacent lateral ventricle in the topography of occipital, temporal, and
      parietal lobes to the right, suggestive of schizencephaly. 

PMID- 24454393
TI  - Meningeal carcinomatosis: a metastasis from gastroesophageal junction
      adenocarcinoma.
AB  - Gastroesophageal adenocarcinoma is a malignant type of cancer, which can
      metastasize to multiple organs. However, there have not been many case reports in
      the literature pertaining the relationship of gastroesophageal adenocarcinoma and
      carcinomatous meningitis. In this case, a 65-year-old African American male with
      a history of dysphagia was initially diagnosed with adenocarcinoma at
      gastroesophageal junction. The patient was treated with both chemotherapy and
      radiation, but chemotherapy was interrupted due to significant weight loss,
      anemia, and sudden onset of change in mental status. Patient was admitted to our
      facility for further evaluation of his neurological symptoms. The patient became
      more confused and delirious during hospital stay, and symptoms could not be
      explained by radiological studies and laboratory values. Therefore, a lumbar
      puncture was done to search for infectious and neoplastic causes that were not
      shown up on Computed Tomography scan (CT) and Magnetic Resonance Imaging scan
      (MRI) of the brain. The cerebrospinal fluid (CSF) cytology showed metastatic
      poorly differentiated adenocarcinoma. The patient's prognosis was poor because
      there is no specific treatment recommendation for primary gastroesophageal cancer
      at this stage. The patient passed away 4 weeks later under hospice care. The goal
      of our case report is to raise awareness of the rare metastatic possibility in
      advanced stage of gastroesophageal adenocarcinoma. In doing so, physicians can
      help educate and prepare family for unfavorable outcomes. 

PMID- 24454394
TI  - Surgical resection of hepatic cystic echinococcosis impaired by preoperative
      diagnosis.
AB  - Cystic echinococcosis (CE) is a rare afferent infectious disease in Japan. This
      paper reports a case of a hepatic cyst being diagnosed after surgical resection.
      A 40-year-old Syrian male was admitted for evaluation of a hepatic cyst. Serum
      antibodies of echinococcosis were negative. Enhanced computed tomography of the
      abdomen revealed a large cystic lesion, 9 cm in diameter, in the left lateral
      sector of the liver, which had many honeycomb-like septa and calcified lesions.
      Magnetic resonance imaging of this lesion revealed high intensity in the T2
      weighted image. We preoperatively diagnosed this lesion as cystadenocarcinoma or
      CE and performed a left hepatectomy. Pathological examination revealed the
      presence of protoscolices in the fluid of the cysts and led to a diagnosis of
      this lesion as CE. In conclusion, on seeing patients with huge hepatic cysts who
      come from an epidemic area, we should consider hepatic CE. 

PMID- 24454395
TI  - Delayed failure after endoscopic staple repair of an anterior spine surgery
      related pharyngeal diverticulum.
AB  - We present a rare complication of endoscopic staple repair of a pharyngeal
      diverticulum related to prior anterior cervical spine surgery. A 70-year-old male
      developed a symptomatic pharyngeal diverticulum 2 years after an anterior
      cervical fusion that was repaired via endoscopic stapler-assisted
      diverticulectomy. He initially had improvement of his symptoms after the stapler
      assisted approach. Three years later, the patient presented with dysphagia and
      was found to have erosion of the cervical hardware into the pharyngeal lumen at
      the site of the prior repair. We present the first reported case of late hardware
      erosion into a pharyngeal diverticulum after endoscopic stapler repair. 

PMID- 24454396
TI  - Restless legs syndrome as the initial presentation of multiple sclerosis.
AB  - The restless legs syndrome (RLS) is a common central nervous system disorder. It
      is characterized by complaints of unpleasant sensation in the legs occurring
      during periods of leg inactivity which worsen or only occur in the evening or at
      night and relieved partially or totally by movement. The RLS may be idiopathic or
      due to secondary causes. It is associated with several pathological or
      physiological conditions. Iron metabolism and dysfunctions of the dopaminergic
      system are the most important factors in the pathophysiology. There are several
      studies suggesting multiple sclerosis as one of the causes of symptomatic RLS.
      Here, we report a case of RLS as the initial presentation of MS. The sudden onset
      of RLS symptoms in our patient suggested the possibility of an underlying cause.
      His diagnostic evaluation excluded other causes of RLS and his clinical course
      suggested that RLS was due to MS. MS with the spinal cord involvement is mostly
      associated with RLS, but any lesion in the hypothalamic-spinal connection may
      cause disinhibition of lower spinal levels, resulting in RLS. RLS as the initial
      presentation of MS reflects that the pathophysiology of RLS in MS is related to
      inflammatory demyelination rather than axonal degeneration. 

PMID- 24454397
TI  - Foreign body aspiration presenting with asthma-like symptoms.
AB  - Aspiration of a foreign body into the tracheobronchial tree is rare in adults. In
      the majority of these cases there is an underlying condition such as mental
      retardation, depressed mental status, impairment in the swallowing reflex,
      neurological impairment, alcohol or sedative abuse, or complications from dental
      manipulations that contributed to the aspiration. These patients are commonly
      misdiagnosed with asthma and typically do not respond to mainstay anti
      inflammatory and/or bronchodilator therapy. We describe the case of a patient
      with a foreign body aspiration in the upper trachea not recognized by
      radiographic studies that presented with asthma-type symptoms. 

PMID- 24454398
TI  - Multifocal Buruli Ulcer Associated with Secondary Infection in HIV Positive
      Patient.
AB  - Buruli ulcer is a chronic and infectious skin disease, caused by Mycobacterium
      ulcerans. It leads to large skin ulceration and sometimes bone infection which is
      responsible for deformities. Here, we report a case of multifocal form of Buruli
      ulcer associated with secondary infection in a 46-year-old human immunodeficiency
      virus (HIV) positive woman. The antimycobacterial drugs combined to surgery
      allowed curing this multifocal case and rose up two relevant issues: the
      susceptibility of immune reconstitution inflammatory syndrome (IRIS) occurrence
      and Mycobacterium dissemination. The deep immune depression, the underline
      biological, and clinical disorders of the patient might contribute to IRIS
      occurrence and Buruli ulcer dissemination. Future investigations have to be
      conducted on the mechanism of IRIS on set and on Mycobacterium ulcerans
      dissemination after ARV drugs initiation and the patient related underline
      clinical or biological disorders. 

PMID- 24454399
TI  - Uncommon cause of paradoxical embolism in a case of scimitar syndrome.
AB  - Scimitar syndrome, a rare congenital cardiopulmonary condition, presents in both
      pediatric and adult populations as an anomalous pulmonary venous return of most
      of the right lung to the inferior vena cava. Recently, asymptomatic adult cases
      have been diagnosed with advances in imaging studies. We report the case of an
      asymptomatic 43-year-old male, with a complex variant scimitar syndrome diagnosed
      by computed tomographic angiography. 

PMID- 24454400
TI  - Primary clear cell adenocarcinoma of a urethral diverticulum treated with
      multidisciplinary robotic anterior pelvic exenteration.
AB  - Primary urethral carcinoma is extremely rare and is marked by a variety of
      clinical symptoms. Primary carcinoma of a urethral diverticulum is still rarer
      and clear cell adenocarcinoma of the urethra is particularly uncommon (Swartz et
      al., 2006). Such infrequency has led to inadequate management guidance in the
      literature for a disease that is often late in presentation and carries
      substantial morbidity and mortality. This treatable but grave disease deserves
      definitive curative treatment. We present the first published instance in which
      it was treated with robotic anterior exenteration. In our case, a 47-year-old
      female was referred to the urology service for investigation of recurring urinary
      tract infections. During the workup, the patient was found to have an advanced
      clear cell urethral adenocarcinoma originating in a urethral diverticulum. We
      discuss the natural history of this condition, its consequences, and the first
      instance of its treatment using robotic anterior pelvic exenteration. 

PMID- 24454401
TI  - A rare case of large skull base meningioma mimicking otitis media with effusion.
AB  - A 48-year-old woman presented with unilateral hearing loss and tinnitus for three
      years associated with middle ear effusion. Previous treatments, including
      antibiotics, corticoids, and transtympanic tube, were ineffective. Otomicroscopy
      showed a greyish retrotympanic mass associated with middle ear effusion. High
      resolution CT scan of the mastoid was in favor of chronic oto-mastoiditis without
      any evidence of tegmen dehiscence. Surgical exploration revealed a polypoid
      greyish mass filling the tympanic cavity. Histological examination
      postoperatively revealed a meningothelial meningioma. Postoperative magnetic
      resonance imaging (MRI) was obtained and showed a large skull base meningioma,
      extending from the clivus anteriorly to the porus acusticus posteriorly with
      middle ear invasion. After discussion with the multidisciplinary tumor board, it
      was managed by stereotactic radiotherapy due to the high surgical associated
      neurovascular risks. In conclusion, middle ear meningioma, although still a rare
      presentation, should be suspected in the presence of atypical chronic OME. 

PMID- 24454402
TI  - Gastric endocrine cell carcinoma coexistent with adenocarcinoma.
AB  - A 69-year-old female presented to our institution with epigastralgia and
      abdominal distension. Upper gastrointestinal series revealed a 5 cm ulcerative
      lesion with irregular margins and elevated distinct borders from the angle to the
      pyloric ring. Gastroendoscopy revealed a Borrmann type 2 tumor. Several biopsied
      specimens revealed proliferation of small and heterogeneous cancer cells with
      rich chromatin and fibrous septum with rich vessels at connective tissues, which
      was confirmed as gastric endocrine cell carcinoma (ECC) on immunostaining with
      chromogranin and synaptophysin. Furthermore, other specimens revealed atypical
      cells forming glandular structures, which were confirmed as well-differentiated
      tubular adenocarcinomas. Distal gastrectomy with D2 lymph node dissection and
      Billroth I reconstruction was performed. Pathological examination of the gross
      specimen revealed that adenocarcinoma comprised <10% of all cancer cells. Close
      analysis of ECC revealed a mixture of small and large cells. According to the WHO
      2010 classification of gastrointestinal neuroendocrine tumors, this gastric tumor
      was diagnosed as neuroendocrine carcinoma. The patient was administered adjuvant
      chemotherapy with cisplatin and etoposide. One year following surgery, follow-up
      abdominal CT revealed multiple liver metastases. The patient received the best
      supportive care but eventually died 18 months after surgery. Here we present this
      case of gastric ECC coexistent with adenocarcinoma. 

PMID- 24454403
TI  - A Patient with Fatal Necrotizing Fasciitis following the Use of Intra-Articular
      Sodium Hyaluronate Injections: A Case Report.
AB  - Introduction. Osteoarthritis, a degenerative joint disease, is a key cause of
      disability around the world and an ever-growing public health concern. Intra
      articular hyaluronic acid viscosupplementation is used as a conservative option
      for osteoarthritis knee pain relief (McArthur et al., 2012; Hootman and Helmick,
      2006; Huang el al., 2011). In general, the literature has shown an excellent
      safety profile for this treatment modality (McArthur et al., 2012; Clegg et al.,
      2013; Hammesfahr et al., 2003; Neustadt et al., 2005; Cohen et al., 2008;
      Neustadt, 2003; Juni et al., 2007; Peterson and Hodler, 2011). Case Presentation.
      In this report, we describe a case of a woman who had received multiple sodium
      hyaluronate injections and developed severe necrotizing fasciitis near the
      injection site. Conclusion. We recommend that clear guidelines for clean
      technique be put in place for use with sodium hyaluronate injections and
      consideration of full sterile technique in immunosuppressed patients. 

PMID- 24454404
TI  - An Unusual Case of Bilateral Vitreous Haemorrhage following Snake Bite.
AB  - A-45-year-old man presented to us with diminution of vision in both eye following
      snake bite. On examination vision in the right eye (RE) was 6/36 and vision in
      left eye (LE) was hand movement positive and fundus examination revealed a
      subhyloid haemorrhage, left eye showed vitreous haemorrhage. Patient was advised
      bed rest, vitamin C tablets and oral steroids. 

PMID- 24454405
TI  - Small bowel hamartoma: a huge diverticulum of small bowel.
AB  - A-20-year old male, with no significant medical history, presented with clinical
      features mimicking a perforated acute appendicitis. Because of features of
      peritonitis, a laparotomy was performed which showed a segment of small bowel
      with multiple large diverticula and mesenteric cysts. A segmental small bowel
      resection was performed. The patient made an uneventful recovery from surgery.
      Histology revealed features of a small bowel hamartoma. 

PMID- 24454407
TI  - Multipotent to pluripotent properties of adult stem cells.

PMID- 24454406
TI  - Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human
      Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ
      Culture System.
AB  - Intervertebral disc (IVD) cell therapy with unconditioned 2D expanded mesenchymal
      stem cells (MSC) is a promising concept yet challenging to realize.
      Differentiation of MSCs by nonviral gene delivery of growth and differentiation
      factor 5 (GDF5) by electroporation mediated gene transfer could be an excellent
      source for cell transplantation. Human MSCs were harvested from bone marrow
      aspirate and GDF5 gene transfer was achieved by in vitro electroporation.
      Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate
      bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination
      of GDF5 gene transfer and 3D culture in alginate showed an upregulation of
      aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for
      discogenesis compared to untransfected cells. The cells encapsulated in alginate
      produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5
      transfected MCS injected into an IVD papain degeneration organ culture model
      showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we
      demonstrate the potential of GDF5 transfected MSC as a promising approach for
      clinical translation for disc regeneration. 

PMID- 24454408
TI  - Mitochondrial PCR-RFLP Assay to Distinguish Triatoma brasiliensis macromelasoma
      from Triatoma brasiliensis brasiliensis Subspecies (Hemiptera: Reduviidae).
AB  - Triatoma brasiliensis sensu lato (s.l.), the main vector of Chagas disease in
      northeastern Brazil, is a species complex comprising four species, one with two
      subspecies (T. brasiliensis brasiliensis, T. brasiliensis macromelasoma, T.
      juazeirensis, T. sherlocki, and T. melanica), and each taxon displaying distinct
      ecological requirements. In order to evaluate the genetic relationships among
      nine T. brasiliensis s.l. populations from northeastern Brazil, we analyzed their
      mitochondrial cytochrome c oxidase subunit 1 sequences and suggested a PCR-RFLP
      assay to distinguish between T. b. macromelasoma and T. b. brasiliensis
      subspecies. All the specimens were morphologically identified as T. b.
      brasiliensis. The resulting phylogenies identified two major clades that are
      congruent with the geographical populations studied. Based on collection sites
      and in accordance with type-location, one clade was identified as the subspecies
      T. b. macromelasoma. The second clade grouped T. b. brasiliensis populations.
      Restriction endonuclease sites were observed in the sequences and used in PCR
      RFLP assays, producing distinct fingerprints for T. b. macromelasoma and T. b.
      brasiliensis populations. The results suggest that these are different species
      and that gene flow occurs only among T. b. brasiliensis populations, possibly
      associated with human activity in the area. 

PMID- 24454409
TI  - Trends of empiric antibiotic usage in a secondary care hospital, karachi,
      pakistan.
AB  - Objectives. (1) To determine the indications, frequency, and types of antibiotics
      used in hospitalized paediatric patients at tertiary care hospital and (2) to
      evaluate whether the prescribed antibiotics were based on the isolation of
      organism and their sensitivity. Study Design. Descriptive observational hospital
      based study. Results. A total of 131 patients were included over 6 months of
      study period, in whom antibiotics were prescribed at the time of admission. The
      majority were between 1 and 5 years of age. M : F ratio was 1 : 1. Fever was the
      commonest symptom (in 84% of cases) followed by gastroenteritis. Blood culture
      was done in 114 cases (87%) and was positive only in 10 (8.8%). The commonest
      organism isolated from blood was Salmonella Typhi. Ceftriaxone was found to be
      the most frequently prescribed antibiotic as an empirical therapy. 102 (77.86%)
      patients received Ceftriaxone, followed by ampicillin. The antibiotics were
      probably used on the basis of clinical condition rather than the result of blood
      culture, as yield of blood culture was quite low. Conclusion. Our study showed an
      unjustified use of antibiotics regardless of the admission and discharge
      diagnosis in acute febrile illnesses. Further on, inappropriate practice of using
      Ceftriaxone was noted in LRTI and pneumonia. Efforts are needed to educate
      physicians about the rational use of antibiotics. 

PMID- 24454410
TI  - A systematic review to investigate whether Angiotensin-(1-7) is a promising
      therapeutic target in human heart failure.
AB  - Context. Heart failure (HF) is a common condition causing much morbidity and
      mortality despite major advances in pharmacological and device therapies.
      Preclinical data suggest a cardioprotective role of Angiotensin-(1-7) in animal
      models of HF. Objective. Perform a systematic review on the effects of
      Angiotensin-(1-7) on humans, focusing on HF. Results. 39 studies were included in
      the review (4 in human HF and (35) in non-HF patients). There is only one
      intervention study on 8 patients with human HF, using Angiotensin-(1-7), with
      forearm blood flow (FBF) as the endpoint. Angiotensin-(1-7) caused no significant
      effect on FBF in this HF study but caused vasodilation in 3 out of 4 non-HF
      studies. In one other non-HF study, Angiotensin-(1-7) infusion led to a
      significant increase in blood pressure in normal men; however, effects were
      <0.03% that of angiotensin II. Cardioprotective effects seen in non-HF studies
      include for instance beneficial actions against atherosclerosis and myocardial
      fibrosis. Conclusions. The main finding of our systematic review is that
      Angiotensin-(1-7) plays an important cardioprotective role in HF in animals and
      in patients without heart failure. More research is required to test the
      hypothesis that Angiotensin-(1-7) benefits patients with heart failure. 

PMID- 24454411
TI  - Structural Features of the Peptide Homologous to 6-25 Fragment of Influenza A PB1
      Protein.
AB  - A mirror-symmetry motif was discovered in the N-terminus of the influenza virus
      PB1 protein. Structure of peptide comprised of the corresponding part of PB1
      (amino acid residues 6-25) was investigated by circular dichroism and in silico
      modeling. We found that peptide PB1 (6-25) in solution assumes beta-hairpin
      conformation. A truncated peptide PB1 (6-13), containing only half of the mirror
      symmetry motif, appeared to stabilize the beta-structure of the original peptide
      and, at high concentrations, was capable of reacting with peptide to form
      insoluble aggregates in vitro. Ability of PB1 (6-13) peptide to interact with the
      N-terminal domain of PB1 protein makes it a potential antiviral agent that
      inhibits PA-PB1 complex formation by affecting PB1 N-terminus structure. 

PMID- 24454412
TI  - Serum Leptin and Adiponectin Levels in Obese and Nonobese Asthmatic School
      Children in relation to Asthma Control.
AB  - There is growing evidence of a positive correlation between asthma and obesity in
      children and adults. Leptin and adiponectin regulate several metabolic and
      inflammatory functions. This study aims to evaluate serum leptin and adiponectin
      concentrations in asthmatic school children to investigate their association with
      obesity and the degree of asthma control. Obese asthmatic (OA) and nonobese
      asthmatic (NOA) children, aged 7 to 14, were randomly enrolled in this
      prospective study. Data on demographic, anthropometric, serum lipids, and
      spirometric measures and allergy status were collected and analyzed. Serum leptin
      was significantly higher (25.8 +/- 11.1 versus 8.7 +/- 11.1; P < 0.0001) and
      adiponectin levels were lower (2.5 +/- 1.2 versus 5.4 +/- 2.9; P < 0.0001) in OA
      compared to NOA children. The uncontrolled group had higher leptin and lower
      adiponectin levels compared to well and partially controlled asthma. BMI was
      positively correlated with leptin (r = 0.79; P < 0.001) and negatively with
      adiponectin (r = -0.73; P < 0.001). Mean BMI and leptin levels were observed to
      be higher in girls compared to boys. Stepwise multiple linear regression analysis
      showed that higher BMI and female gender had significant effect on serum leptin
      levels. Among asthmatic children higher serum leptin and lower adiponectin levels
      were significantly associated with obesity and showed no significant association
      with degree of asthma controls. 

PMID- 24454413
TI  - Traditional coping strategies and disaster response: examples from the South
      Pacific region.
AB  - The Pacific Islands are vulnerable to climate change and increased risk of
      disasters not only because of their isolated and often low lying geographical
      setting but because of their economic status which renders them reliant on donor
      support. In a qualitative study exploring the adaptive capacity of Pacific Island
      Countries (PICs) across four countries, Cook Islands, Fiji, Samoa, and Vanuatu,
      it was clear that traditional coping strategies are consistently being applied as
      part of response to disasters and climate changes. This paper describes five
      common strategies employed in PICs as understood through this research:
      recognition of traditional methods; faith and religious beliefs; traditional
      governance and leadership; family and community involvement; and agriculture and
      food security. While this study does not trial the efficacy of these methods, it
      provides an indication of what methods are being used and therefore a starting
      point for further research into which of these traditional strategies are
      beneficial. These findings also provide important impetus for Pacific Island
      governments to recognise traditional approaches in their disaster preparedness
      and response processes. 

PMID- 24454414
TI  - Environment and health in contaminated sites: the case of Taranto, Italy.
AB  - The National Environmental Remediation programme in Italy includes sites with
      documented contamination and associated potential health impacts (National
      Priority Contaminated Sites-NPCSs). SENTIERI Project, an extensive investigation
      of mortality in 44 NPCSs, considered the area of Taranto, a NPCS where a number
      of polluting sources are present. Health indicators available at municipality
      level were analyzed, that is, mortality (2003-2009), mortality time trend (1980
      2008), and cancer incidence (2006-2007). In addition, the cohort of individuals
      living in the area was followed up to evaluate mortality (1998-2008) and
      morbidity (1998-2010) by district of residence. The results of the study
      consistently showed excess risks for a number of causes of death in both genders,
      among them: all causes, all cancers, lung cancer, and cardiovascular and
      respiratory diseases, both acute and chronic. An increased infant mortality was
      also observed from the time trends analysis. Mortality/morbidity excesses were
      detected in residents living in districts near the industrial area, for several
      disorders including cancer, cardiovascular, and respiratory diseases. These
      coherent findings from different epidemiological approaches corroborate the need
      to promptly proceed with environmental cleanup interventions. Most diseases
      showing an increase in Taranto NPCS have a multifactorial etiology, and
      preventive measures of proven efficacy (e.g., smoking cessation and
      cardiovascular risk reduction programs, breast cancer screening) should be
      planned. The study results and public health actions are to be communicated
      objectively and transparently so that a climate of confidence and trust between
      citizens and public institutions is maintained. 

PMID- 24454415
TI  - Impact of water, sanitation, and hygiene interventions on improving health
      outcomes among school children.
AB  - PURPOSE: This review was done to explore the impact of water treatment, hygiene,
      and sanitary interventions on improving child health outcomes such as
      absenteeism, infections, knowledge, attitudes, and practices and adoption of
      point-of-use water treatment. METHODS: A literature search was conducted using
      the databases PubMed and Google scholar for studies published between 2009 and
      2012 and focusing on the effects of access to safe water, hand washing
      facilities, and hygiene education among school-age children. Studies included
      were those that documented the provision of water and sanitation in schools for
      children less than 18 years of age, interventions which assessed WASH practices,
      and English-language, full-text peer reviewed papers. RESULTS: Fifteen studies
      were included in the final analysis. 73% (n = 11) of the studies were conducted
      in developing countries and were rural based (53%, n = 8). The child's age,
      gender, grade level, socioeconomic index, access to hygiene and sanitary
      facilities, and prior knowledge of hygiene practices were significantly
      associated with the outcomes. Nutrition practices which are key factors
      associated with the outcomes were rarely assessed. CONCLUSION: Further research
      is required to assess the long-term impact of such interventions in different
      settings.

PMID- 24454416
TI  - Designing fuzzy algorithms to develop healthy dietary pattern.
AB  - BACKGROUND: Fuzzy logic, a mathematical approach, defines the percentage of
      desirability for recommended amount of food groups and describes the range of
      intakes, from deficiency to excess. OBJECTIVES: The purpose of this research was
      to find the best fuzzy dietary pattern that constraints energy and nutrients by
      the iterative algorithm. MATERIALS AND METHODS: An index is derived that reflects
      how closely the diet of an individual meets all the nutrient requirements set by
      the dietary reference intake. Fuzzy pyramid pattern was applied for the energy
      levels from 1000 to 4000 Kcal which estimated the range of recommended servings
      for seven food groups including fruits, vegetables, grains, meats, milk, oils,
      fat and added sugar. RESULTS: The optimum (lower attention - upper attention)
      recommended servings per day for fruits, vegetables, grain, meat, dairy, and oils
      of the 2000 kcal diet were 4.06 (3.75-4.25), 6.69 (6.25-7.00), 5.69 (5.75-6.25),
      4.94 (4.5-5.2), 2.75(2.50-3.00), and 2.56 (2.5-2.75), respectively. The fuzzy
      pattern met most recommended nutrient intake levels except for potassium and
      vitamin E, which were estimated at 98% and 69% of the dietary reference intake,
      respectively. CONCLUSIONS: Using fuzzy logic provides an elegant mathematical
      solution for finding the optimum point of food groups in dietary pattern.

PMID- 24454417
TI  - Evaluation of radiation doses delivered in different chest CT protocols.
AB  - BACKGROUND: There are differences in the reference diagnostic levels for the
      computed tomography (CT) of the chest as cited in different literature sources.
      The doses are expressed either in weighted CT dose index (CTDIVOL) used to
      express the dose per slice, dose-length product (DLP), and effective dose (E).
      The purpose of this study was to assess the radiation dose used in Low Dose
      Computer Tomography (LDCT) of the chest in comparison with routine chest CT
      examinations as well as to compare doses delivered in low dose chest CT with
      chest X-ray doses. MATERIAL/METHODS: CTDIVOL and DLP doses were taken to analysis
      from routine CT chest examinations (64 MDCT TK LIGHT SPEED GE Medical System)
      performed in 202 adult patients with FBP reconstruction: 51 low dose, 106
      helical, 20 angio CT, and 25 high resolution CT protocols, as well as 19 helical
      protocols with iterative ASIR reconstruction. The analysis of chest X-ray doses
      was made on the basis of reports from 44 examinations. RESULTS: Mean values of
      CTDIVOL and DLP were, respectively: 2.1 mGy and 85.1 mGy.cm, for low dose, 9.7
      mGy and 392.3 mGy.cm for helical, 18.2 mGy and 813.9 mGy.cm for angio CT, 2.3 mGy
      and 64.4 mGy.cm for high resolution CT, 8.9 mGy. and 317.6 mGy.cm for helical
      ASIR protocols. Significantly lower CTDIVOL and DLP values were observed for low
      dose and high resolution CT versus the remaining CT protocols; doses delivered in
      CT ASIR protocols were also lower (80-81%). The ratio between medial doses in low
      dose CT and chest X-ray was 11.56. CONCLUSIONS: Radiation dose in extended chest
      LDCT with parameters allowing for identification of mediastinal structures and
      adrenal glands is still much lower than that in standard CT protocols. Effective
      doses predicted for LDCT may exceed those used in chest X-ray examinations by a
      factor of 4 to 12, depending on LDCT scan parameters. Our results, as well as
      results from other authors, suggest a possibility of reducing the dose by means
      of iterative reconstruction. Efforts towards further dose reduction which would
      permit replacing chest X-ray with low dose CT in certain research screening
      projects should be encouraged.

PMID- 24454418
TI  - Effect of methylphenidate and folic Acid on ADHD symptoms and quality of life and
      aggression: a randomized double blind placebo controlled clinical trial.
AB  - OBJECTIVE: This clinical trial examines the effect of augmentation of
      methylphenidate (MPH) with folic acid to improve quality of life, and to treat
      aggression and ADHD symptoms. METHOD: Participants of this eight week randomized
      double blind placebo controlled clinical trial were 49 children with ADHD. They
      were randomly assigned into one of the two groups: the first group receiving
      methylphenidate (10 to 20mg/day) plus folic (5mg/day), and the second group
      receiving methylphenidate plus placebo. Parent-reported ADHD symptoms and Overt
      Aggression Scale score were the outcome measures. Quality of life was assessed as
      well. Assessments were performed at pre-intervention, and at one month and two
      months after starting the interventions using repeated measure analysis. RESULTS:
      The mean age of children was 9.6(2.7) years. Age and gender were not associated
      with the groups. ADHD symptoms significantly decreased in both groups during the
      trial. However, no difference was observed between the groups. Moreover,
      aggression non-significantly decreased in both groups. Meanwhile, there was no
      difference between the two groups in efficacy for treating different types of
      aggressive behaviors including: verbal aggression, physical aggression against
      people, physical aggression against properties or objects, and aggression against
      self (self-injurious behavior). While methylphenidate improved quality of life of
      children with ADHD, folic acid did not improve it more than placebo. Both
      medications were well tolerated. CONCLUSION: considering the marked limitations
      of this trial, this primarily report suggests that methylphenidate may improve
      ADHD symptoms and the quality of life of children with ADHD. Current evidence
      does not support that folic acid as an adjuvant is effective for treating ADHD
      symptoms or aggression, or the improving quality of life of children with ADHD.

PMID- 24454419
TI  - Effectiveness of compassionate mind training on depression, anxiety, and self
      criticism in a group of Iranian depressed patients.
AB  - OBJECTIVE: The purpose of this study was to examine the effectiveness of
      compassionate mind training (CMT) on symptoms of depression and anxiety in
      Iranian depressed sufferers. METHOD: Nineteen depressed patients aged 20 to 40
      (Beck Depression Inventory value >= 20) were randomly assigned into two groups.
      The experimental group participated in 12 sessions of group therapy based on Paul
      Gilbert's manual of CMT. The control group was given no intervention. The
      participants were assessed by Beck Depression Inventory-II (BDI-II), Anxiety
      Scale (AS), and Levels of Self-Criticism (LSCS) questionnaires at the beginning
      and immediately after the intervention. To follow-up the therapeutic effect of
      CMT, the three questionnaires were answered again by participants two months
      after the end of the intervention. Data were analyzed by independent samples t
      test. RESULTS: The results revealed that CMT significantly decreases depression
      (P < 0.05) and anxiety score (P < 0.05) in the follow-up study, but not
      immediately after the intervention. Although CMT decreased self-criticism, this
      effect was marginally insignificant. CONCLUSION: The findings indicated that CMT
      could alleviatedepression and anxiety in a group of Iranian depressed patients.

PMID- 24454420
TI  - The Relationship between Behavioral Activation/Inhibition Systems (BAS/BIS) and
      Bullying/ Victimization Behaviors among Male Adolescents.
AB  - OBJECTIVE: This research was conducted to investigate the relationship between
      behavioral activation-inhibition systems and bullying-victimization behaviors
      among adolescents. METHOD: This was a correlational and cross-sectional study.
      Two hundred and thirty school boys were selected randomly by multistage cluster
      sampling method, and participated in this research. This sample responded to a
      demographic questionnaire, the Revised Olweus Bully/ Victim questionnaire and the
      child version of behavioral inhibition/activation systems Scale in their
      classrooms and in the presence of the researcher. The collected data were
      analyzed by Pearson's correlation and multiple regressions. RESULT: The results
      showed that bullying and victimization were correlated with both behavioral
      activation and behavioral inhibition systems (p < 0.01). The results also showed
      that 18% of the variance in victimization and 31% of the variance in bullying
      were explained by behavioral inhibition and behavioral activation systems
      respectively. CONCLUSION: The results of this study implied that BAS and BIS may
      play a role in the manifestation of bullying in adolescents.

PMID- 24454421
TI  - Response inhibition and cognitive appraisal in clients with acute stress disorder
      and posttraumatic stress disorder.
AB  - OBJECTIVE: The purpose of the present study was to compare response inhibition
      and cognitive appraisal in clients with acute stress disorder, clients with
      posttraumatic stress disorder, and normal individuals. METHOD: This was a
      comparative study. The sample consisted of 40 clients with acute stress disorder,
      40 patients with posttraumatic stress disorder, and 40 normal individuals from
      Mazandaran province selected through convenience sampling method. Data were
      collected using Composite International Diagnostic Interview, Stroop Color-Word
      Test, Posttraumatic Cognitions Inventory, and the Impact of Event Scale. RESULTS:
      Results showed that individuals with acute stress disorder are less able to
      inhibit inappropriate responses and have more impaired cognitive appraisals
      compared to those with posttraumatic stress disorder. Moreover, results showed
      that response inhibition and cognitive appraisal explain 75% of the variance in
      posttraumatic stress disorder symptoms and 38% of the variance in posttraumatic
      stress disorder symptoms. CONCLUSION: The findings suggest that response
      inhibition and cognitive appraisal are two variables that influence the severity
      of posttraumatic stress disorder and acute stress disorder symptoms. Also, these
      results have important implications for pathology, prevention, and treatment of
      posttraumatic stress disorder and acute stress disorder.

PMID- 24454422
TI  - Comparing Iconic Memory in Children with and without Attention Deficit
      Hyperactivity Disorder.
AB  - OBJECTIVE: Children with attention deficit hyperactivity disorder (ADHD) do not
      process most information due to inattention and loss of the opportunity to save
      and retrieve information. Therefore, these children experience memory impairment.
      Although visual memory has been previously studied in children with ADHD, iconic
      memory in these children has been less evaluated. We aimed to study the
      possibility of iconic memory impairment in children with ADHD, and compare the
      results with that of children without ADHD. METHODS: The experimental group of
      this study were 6-9 year-old children who referred to the Imam Hosein Clinic and
      were diagnosed as having ADHD by a psychiatrist during 2011-2012 (n = 30).The
      subjects were interviewed clinically by a psychologist; and in order to diagnose
      ADHD, their parents and teachers were asked to complete the child symptom
      inventory-4 (CSI-4). The comparison group were 6-9 year-old children without ADHD
      who studied in 1st and 2nd educational district of Yazd (n = 30). Subjects'
      iconic memory was assessed using an iconic memory task. Repeated measure ANOVA
      was used for data analysis. RESULTS: Based on the iconic memory test, the mean
      score of ADHD children was significantly lower than that of children without ADHD
      (P < 0.001). Moreover, the performance of the experimental group differed
      significantly when the duration of the presentation differed from 50 ms to 100 ms
      as compared to the control group (P < 0.001). The number of correct answers
      increased in the experimental group as the duration of presentation increased.
      However, children with ADHD scored less than children without ADHD at 50 ms as
      well as 100 ms. The means of ADHD children increased as the duration of the
      presentation increased from 50 ms to 100 ms to 300 ms (P < 0.001). CONCLUSION:
      Visual memory is weaker in children with ADHD, and they have weaker performance
      than normal children in both visual and auditory symbols at presentation
      durations of 50 and 100 ms. The performance of ADHD children improves as the
      stimulation time increases.

PMID- 24454423
TI  - Prevalence and Associated Factors of Physical, Verbal and Relational Aggression
      among Iranian Preschoolers.
AB  - OBJECTIVE: Childhood aggression may lead to severe social disorders in
      adolescence and adulthood. Different psychiatric approaches are focused on
      preschool aged aggressive children. The aim of this study was to estimate the
      prevalence and associated factors of childhood direct and indirect aggression.
      METHODS: In this cross sectional study a total of 1403 children attending 43
      kindergartens were assessed. Data were collected through a structured 46-item
      questionnaire investigating symptoms of physical, verbal and relational
      aggression which was completed by parents and teachers of day-care centers.
      Complex sample survey analysis and multivariate logistic regression method were
      used for data analysis. RESULTS: According to parents' rating, the prevalence of
      physical,verbal and relational aggression, was 9.9% (95% CI=7.4%-12.4%), 6.3%
      (95% CI=5.0% -7.6%) and 1.6% (95%CI=1.0%-2.2%), respectively; while based on
      teachers' rating the prevalence of physical,verbal and relational aggression were
      10.9% (95% CI=8.9% -12.9%), 4.9%(95% CI=3.8% -6.0%) and 6% (95% CI=4.4% -7.6%),
      respectively. A wide range of family environment factors including living with a
      single parent, having a working mother, death of someone close to the child, and
      having less educated mother were significantly associated with different types of
      aggression; additionally, there was some evidence of a relationship between sex
      of the children and physical aggression, after controlling for other variables (p
      < 0.05). CONCLUSION: This study revealed that children's family environment
      alongside internal factors plays an important role as an external factor in
      determining the child's potential aggressive behavior. Given this, to better
      prevent the aggressive behavior of children, intervention strategies should be
      planned for families and caregivers; specially mothers should receive training to
      use such strategies.

PMID- 24454424
TI  - Comparison of two different curricula in psychiatry clerkship at tehran
      university of medical sciences.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of a new
      psychiatry clerkship curriculum which was designed to improve the knowledge and
      skills of medical students of Tehran University of Medical Sciences (TUMS), Iran.
      METHODS: This quasi-experimental study was conducted in two consecutive semesters
      from February 2009 to January 2010. In total, 167 medical students participated
      in the study. In the first semester, as the control group, the clerks' training
      was based on the traditional curriculum. In the next semester, we constructed and
      applied a new curriculum based on the SPICES model (student-centered, problem
      based, integrated, community-based, elective and systematic).At the end of the
      clerkship, the students were given two exams: Multiple Choice Questions (MCQ) to
      assess their knowledge, and Objective Structured Clinical Examination (OSCE) to
      assess their skills. Baseline data and test performance for each student were
      analyzed. RESULTS: Compared to the control group, students in the intervention
      group showed significantly higher OSCE scores (P= 0.01). With respect to MCQ
      score, no significant difference was found between the two groups. CONCLUSIONS:
      The results suggest that the revised curriculum is more effective than the
      traditional one in improving the required clinical skills in medical students
      during their psychiatry clerkship.

PMID- 24454425
TI  - Palatal-Myoclonus as a Presentation of Hashimoto Encephalopathy: an interesting
      case report.
AB  - OBJECTIVE: Hashimoto encephalopathy (HE) is known as a steroid- responsive
      encephalopathy associated with autoimmune thyroiditis or nonvascular inflammation
      related autoimmune meningoencephalitis. The average age of onset of HE is
      approximately 50 years; and it is more common in women. The onset of HE may be
      acute or subacute. The course of most HE cases is relapsing and remitting, which
      is similar to that of vasculitis and stroke. METHODS: In this article, we present
      a previously healthy 32 years old;veterinarian male with palatal myoclonus, as a
      rare presentation of this disorder, and review the neurologic aspects of
      hashimoto encephalitis. RESULTS: The clinical presentation of HE is characterized
      by progressive cognitive decline tremor, transient aphasia, seizures, abnormal
      gait, sleep disorder and stroke-like episodes. Myoclonus, either generalized or
      multifocal, and tremor, often of the bilateral upper extremities, is the most
      frequently observed involuntary movements in HE. CONCLUSION: The rapidly
      progressive cognitive dysfunction and encephalopathies observed.

PMID- 24454426
TI  - Visceral leishmaniasis in Iran: Review of the Epidemiological and Clinical
      Features.
AB  - Visceral leishmaniasis (VL) is a life-threatening vector-borne parasitic disease
      is distributed in some parts of the new world and old world. The disease is
      endemic in different parts of Iran. This review article has been focused on major
      topics of epidemiological aspects and clinical features of VL in Iran for the
      period of 2002 through 2012. For the detection of VL in humans as well as animal
      reservoir hosts, anti-Leishmania antibodies were detected using direct
      agglutination test (DAT) as a validated serological test. Parasitological
      examinations were performed on suspected VL patients as well as canines and
      rodents. Different molecular methods were used for identification of species and
      genotype/ or strain of Leishmania spp. isolated from infected humans, animal
      reservoir hosts and vectors. Altogether, 1698 out of 36081 (4.7%) human serum
      samples collected from 5 distinct geographical zones showed anti-Leishmania
      antibodies at titers >= 1:3200 using DAT. The majority of VL cases in the endemic
      areas were found among children up to 12 years old. Almost 75% of DAT-positive
      cases (>=1:3200) in endemic areas showed clinical signs and symptoms. Predominant
      signs and symptoms in 217 hospitalized patients with DAT positive (>=1:3200)
      results included paleness (99.5%), fever (96.9%), splenomegaly (91.5%),
      hepatomegaly (53.6%) and lymphadenopathy (21.1%). Integrated VL surveillance
      system in primary care using DAT, could decrease mortality and morbidity of the
      disease in the VL endemic areas of the northwestern Iran. Out of 7204 serum
      samples collected from domestic dogs in various geographical locations of Iran,
      879 (12.2%) were DAT sero-positive at titers >= 1:320. L. infantum as the
      principal causative agent of the disease was isolated from infected humans,
      domestic and wild canines and rodents. The principal animal reservoir hosts of
      the infection are domestic and wild canines. Ph. kandelakii, Ph. perfiliewi
      transcaucasicus, Ph. tobbi in northwestern Iran; Ph. major s.l. (=Ph. neglectus),
      Ph. keshishiani, and Ph. alexandri in southern parts of Iran were molecularly
      and/or parasitologically positive for L. infantum infections. The zoonotic form
      of VL (ZVL) caused by L. infantum occurs sporadically in all geographical zones
      of Iran but in northwestern and southern parts of the country the disease is
      endemic. DAT as an appropriate and potential tool has been used for sero
      diagnosis and sero-epidemiological of VL among humans as well as domestic and
      wild canines. 

PMID- 24454427
TI  - Downregulation of Calcineurin Gene Is Associated with Glucantime((r)) Resiatance
      in Leishmania infantum.
AB  - BACKGROUND: Pentavalent antimonials are the first line drugs for the treatment of
      leishmaniasis. Unresponsiveness of Leishmania spp. to antimonial drugs is a
      serious problem in some endemic areas. Investigations on molecular mechanisms
      involved in drug resistance are essential for monitoring and managing of the
      disease. Cal-cineurin is an essential protein phosphatase for number of signal
      transduction pathways in eukaryotic cells and it has a mediated role in
      apoptosis. This study aimed to determine of biomarker(s) in Glucantime((r))
      resiatance strain of L. infan-tum. METHODS: We used cDNA amplified fragment
      length polymorphism (cDNA-AFLP) and real time-RT PCR assays to compare gene
      expression profiles at the mRNA levels in resistant and susceptible L. infantum
      field isolates. RESULTS: The cDNA-AFLP results showed downlegulation of
      calcineurin in resis-tant isolate in comparison with susceptible one. Significant
      downregulation of cal-cineurin (0.42 fold) (P<0.05) was found in resistant
      isolate compared to susceptible one by Real time-RT PCR. CONCLUSION: This is the
      first report of calcineurin implication in Glucantime((r)) drug resistance of
      field (natural) isolate of L. infantum. Downregulation of calcineurin could
      protect parasites from antimonial-induced apoptosis.

PMID- 24454428
TI  - In Vitro and In Vivo Potential of RH Strain of Toxoplasma gondii (Type I) in
      Tissue Cyst Forming.
AB  - BACKGROUND: Based on recent studies, there are controversial reports on the
      capacity of tissue cyst forming of Toxoplasma gondii RH strain. In this study,
      the capacity was evaluated by in vivo and in vitro experiments. METHODS: RH
      strain was subcutaneously inoculated to ten Wistar rats. After one month, their
      blood, brain, tongue and diaphragm were collected and evaluated by MAT, PCR,
      pathological and bioassay methods. The parasite was cultivated in the cell
      monolayer. To change to bradyzoite, the media pH was altered to 6.8. Biological
      aspect of the bradyzoites was evaluated by incubation in acidic pepsin and it's
      inoculation in ten BALB/c mice. RESULTS: All rats showed antibodies to Toxoplasma
      at titers >=1:320 but no DNA and tissue cyst were detected in the tissues.
      Following intraperitoneal inoculation of rats' brain homogenate into BALB/c mice,
      no infection was established in none of the animals. During presence of cell
      culture, in acid media for a 3-5 days period, cyst-like structures were noticed
      when they were stained with PAS. The visible bradyzoites in the cysts that were
      incubated in acid pepsin medium were not able to kill any mice. CONCLUSION: This
      study confirmed that Iranian RH strain has lost the potential of tissue cyst
      forming in rats and bradyzoites cultivated in cell culture lost their resistance
      to acidic condition, so this strain can be a candidate for future vaccine
      researches.

PMID- 24454429
TI  - Identification of Echinococcus granulosus Strains in Isolated Hydatid Cyst
      Specimens from Animals by PCR-RFLP Method in West Azerbaijan - Iran.
AB  - BACKGROUND: The aim of this study was DNA extraction from protoscolecses of
      Echinococcus granulosus and identification of these strains in West-Azerbaijan
      Province, north western Iran. METHODS: Thirty one livestock isolates from sheep
      and cattle were collected from abattoirs of the province. To investigate the
      genetic variation of the isolates, after DNA extraction by Glass beads-phenol
      chloroform method; PCR-RLFP analysis of rDNA-ITS1 was performed using three
      different restriction enzymes of Taq 1, Rsa 1 and Alu 1. RESULT: Amplified PCR
      products for all isolates were 1000bp band which is expected band in sheep
      strains (G1-G3 complex). The results of RFLP analysis also were the same for all
      isolates. PCR-RFLP patterns restriction enzymes were identical as follows, Rsa1
      bands under UV showed two bands approximately 655bp and 345bp. Alu1 bands were as
      follows: two approximately 800bp and 200bp and Taq1 did not cut any region and
      bands were approximately 1000 bp in all samples. CONCLUSIONS: Based on PCR-RFLP
      patterns of ITS1 fragment produced with endonucleases enzyme digestion in animal
      isolates, it can be concluded that a single strain of E. granulosus (sheep strain
      or G1-G3 complex) is dominant genotype in this province.

PMID- 24454430
TI  - Identification of leishmania species using PCR assay on giemsa-stained slides
      prepared from cutaneous leishmaniasis patients.
AB  - BACKGROUND: Leishmaniasis is a group of diseases that are created by
      intracellular parasites of Leishmania. Cutaneous leishmaniasis is considered as
      one of the health problems in some provinces of Iran. METHODS: In this study, a
      total of 178 Giemsa-stained slides from confirmed cases of cutaneous
      leishmaniasis were examined. The slides were prepared from the patients with
      cutaneous leishmaniasis that referred to health centers and infected during the
      epidemic of cutaneous leishmaniasis in Poldokhtar city, Lorestan Province, Iran
      in 2006.Genomic DNA from each slide was extracted. After DNA extraction, ITS-PCR
      was used. RESULTS: Out of 178 slides, 129 (72.47%) samples had a band in the
      range of 485 bp and 49 (27.53%) samples 626 bp that matched L. tropica and L.
      major standard samples, respectively. CONCLUSION: This study showed that
      Leishmania DNA could be efficiently extracted and amplified even from old Giemsa
      stained microscopic slides that were stored more than 6 yr. In this study was
      shown that both L. tropica and L. major species exist in Lorestan Province.

PMID- 24454431
TI  - Investigation of Possible Correlation between Giardia duodenalis Genotypes and
      Clinical Symptoms in Southwest of Iran.
AB  - BACKGROUND: Giardia duodenalis is one of the most important human enteric
      parasites throughout the world. Clinical symptoms of this parasite vary from
      asymptomatic infection to chronic diarrhea. Still it is not clear, whether
      different types of pathogenesis are due to different strains of organism or to
      variable host factors. The purpose of this study was to investigate possible
      correlation of clinical symptoms with assemblages among symptomatic and
      asymptomatic cases collected from southwest of Iran. METHODS: Fecal samples were
      collected from 100 symptomatic and asymptomatic cases, which were positive for G.
      duodenalis. The samples were subjected to semi-nested PCR and RFLP for gdh gene.
      RESULTS: Among symptomatic patients, 54% had mixed genotypes AII and BIII, 28%
      and 18% of samples indicated assemblages BIII and AII, respectively. In contrast,
      among asymptomatic cases, 64%, 26% and 10%samples had mixed genotypes, BIII and
      AII assemblages, respectively. Statistical analysis using Chi- Square test showed
      that there was no significant correlation between assemblage and clinical
      symptoms in current study. CONCLUSION: High prevalence of mixed infection in both
      groups may affect this conclusion, therefore further study in more details are
      necessary to clarify these finding. Additionally, it is important to carry out
      investigations regarding human host factors as well.

PMID- 24454432
TI  - Evaluation of a Possible Synergistic Effect of Meglumine Antimoniate with
      Paromomycin, Miltefosine or Allopurinol on in Vitro Susceptibility of Leishmania
      tropica Resistant Isolate.
AB  - BACKGROUND: Pentavalent antimonials are still the first choice treatment for
      leishmaniasis, but with low efficacy and resistance is emerging. In the present
      study, the effect of meglumine antimoniate (MA, Glucantime) combined with
      paromomycin, miltefosine or allopurinol on in vitro susceptibility of Leishmania
      tropica resistant isolate was evaluated. METHOD: The drugs were obtained from
      commercial sources and diluents of each drug in medium were prepared on the day
      of experiment. J774 A.1 murine macrophage cell lines were attached to the
      cultured on slide and incubated at 37  degrees C with 5% CO2 for 24 h. Then the
      stationary phase promastigotes were added to the cells and after 4 hrs of
      incubation different concentrations of MA, paromomycin, miltefosine or
      allopurinol were added and incubated for an additional of 72 h. Then the slides
      were dried and fixed with methanol, stained by Giemsa and studied under a light
      microscope. Drug activity was evaluated by assessing the macrophage infection
      rate and the number of amastigotes per infected macrophage was done by examining
      100 macrophages. The experiment was done in triplicates. RESULT: Various
      concentrations of MA along with paromomycin, miltefosine or allopurinol
      significantly inhibited (P<0.01) the proliferation of L. tropica amastigote stage
      in the macrophage cell line as compared with MA alone or positive control.
      CONCLUSION: Combination of Glucantime with paromomycin, miltefosine or
      allopurinol showed a synergistic effect on the clinical isolate of L. tropica in
      vitro. Use of combination therapy is a new hope and a logical basis for therapy
      of the patients with cutaneous leishmaniasis. Further investigations are needed
      to evaluate the therapeutic effects of these drugs on the CL patients.

PMID- 24454433
TI  - Ferredoxin Gene Mutation in Iranian Trichomonas vaginalis Isolates.
AB  - BACKGROUND: Trichomonas vaginalis causes trichomoniasis and metronidazole is its
      chosen drug for treatment. Ferredoxin has role in electron transport and
      carbohydrate metabolism and the conversion of an inactive form of metronidazole
      (CO) to its active form (CPR). Ferredoxin gene mutations reduce gene expression
      and increase its resistance to metronidazole. In this study, the frequency of
      ferredoxin gene mutations in clinical isolates of T.vaginalis in Tehran has been
      studied. METHODS: Forty six clinical T. vaginalis isolates of vaginal secretions
      and urine sediment were collected from Tehran Province since 2011 till 2012. DNA
      was extracted and ferredoxin gene was amplified by PCR technique. The ferredoxin
      gene PCR products were sequenced to determine gene mutations. RESULTS: In four
      isolates (8.69%) point mutation at nucleotide position -239 (the translation
      start codon) of the ferredoxin gene were detected in which adenosine were
      converted to thymine. CONCLUSION: Mutation at nucleotide -239 ferredoxin gene
      reduces translational regulatory protein's binding affinity which concludes
      reduction of ferredoxin expression. For this reduction, decrease in activity and
      decrease in metronidazole drug delivery into the cells occur. Mutations in these
      four isolates may lead to resistance of them to metronidazole.

PMID- 24454434
TI  - Immunoproteomic Analysis of the Excretory-Secretory Proteins from Spirometra
      mansoni Sparganum.
AB  - BACKGROUND: Sparganosis is caused by the invasion of Spirometra sparganum into
      various tissues/organs. Subcutaneous sparganosis can be diagnosed by biopsy,
      while visceral/cerebral sparganosis is not easy to be diagnosed. The diagnosis
      depends largely on the detection of specific anti-sparganum antibodies. The
      specificity of the ELISA could be increased by using S. mansoni sparganum
      excretory-secretory (ES) antigens, but it also had the cross-reactions with sera
      of patients with cysticercosis or paragonimiasis. The aim of this study was to
      identify early specific diagnostic antigens in S. mansoni sparganum ES proteins.
      METHODS: The sparganum ES proteins were analyzed by two-dimensional
      electrophoresis (2-DE) and Western blot probed with early sera from infected mice
      at 14 days post-infection. The immunoreactive protein spots were characterized by
      MALDI-TOF/ TOF-MS. RESULTS: A total of approximately 149 proteins spots were
      detected with isoelectric point (pI) varying from 3 to 7.5 and molecular weight
      from 20 to 115 kDa and seven protein spots with molecular weight of 23-31 kDa
      were recognized by the infection sera. Three of seven spots were successfully
      identified and characterized as the same S. mansoni protein (cysteine protease),
      and the proteins of other 4 spots were not included in the databases. CONCLUSION:
      The cysteine protease from S. mansoni ES proteins recognized by early infection
      sera might be the early diagnostic antigens for sparganosis.

PMID- 24454435
TI  - Echinococcosis/Hydatidosis in ilam province, Western iran.
AB  - BACKGROUND: Hydatidosis is a zoonotic disease of global prevalence. It causes
      considerable health problems and economic losses throughout the world, including
      Iran. The objective of this study was to assess the current status of
      echinococcosis/hydatidosis in the province of Ilam (western Iran). METHODS: From
      April to September 2011, 65 stray dogs were collected from urban and rural areas
      of Ilam City. Parasites were isolated from the dogs and stained with carmine. A
      taxonomic study was carried out by measuring different parts of helminths. Meat
      inspection documents from slaughterhouses in Ilam were used to assess the
      prevalence of hydatidosis during a 3-year period in sheep, cattle, and goats.
      ELISA test was used to detect the presence of antibodies to hydatidosis in human
      sera. Clinical records from 2000 to 2010 of either treated or diagnosed patients
      from public hospitals of this province were reviewed. RESULTS: The prevalence of
      Echinococcus granulosus infection in stray dogs was 9%. A total of 81,726 animals
      were assessed for hydatidosis; 2.94% (2403 cases) had liver hydatidosis and 2.34%
      (1918 cases) had lung hydatidosis. Within a 10-year period, 140 patients (91
      females and 49 males) were treated for hydatidosis. Of 1200 human sera, 2.25% (27
      patients) were seropositive for hydatidosis. CONCLUSION: Hydatidosis is endemic
      in Ilam Province especially in rural area. The health and economic losses caused
      by the disease are significant; thus, our efforts need to be focused on the
      control of this disease.

PMID- 24454436
TI  - Seasonal and Geographic Distribution of Cercarial Infection in Lymnaea gedrosiana
      (Pulmunata: Lymnaeidae) In North West Iran.
AB  - BACKGROUND: Trematodes are a diverse group of endoparasites which require
      molluscan and vertebrate animals as intermediate and definitive hosts in their
      life cycle. The present study was carried out to determine the diversity and
      geographic distribution of infection with trematodes'cercariae in the snail
      Lymnaea gedrosiana from north-west Iran. METHODS: A total number of 6759
      Lymnaeidae snails were collected from 28 snail habitats; of these L. gedrosiana
      was the prevalent snail (74.37%) which examined for cercarial infection by
      shedding method. RESULTS: The overall infection rate was 8.03%. The most frequent
      trematodes cercariae in the snail were xiphidiocercariae (81.98%), furcocercariae
      (32.26%), echinostome cercariae (5.19%), and monostome cercariae (1.24%). The
      highest infection rate in L. gedrosiana (100%) was with echinostome cercariae
      from Golestaneh in autumn. CONCLUSION: Due to the important role of pond snails
      in transmission of cercariae to fish as a source of zoonotic diseases, it is
      essential to estimate the distribution and abundance of the snails and the rate
      of their infection with different trematodes' cercariae, and establish control
      programs in each region.

PMID- 24454437
TI  - Cutaneous leishmaniasis in suspected patients referred to the center for research
      and training in skin diseases and leprosy, tehran, iran from 2008 to 2011.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is a major health problem in many parts
      of Iran, although diagnosis of CL especially in the endemic area is easy, but
      treatment and management of the disease is a global dilemma. Diagnosis of CL in
      non-endemic area is not as simple as in endemic foci. In this study, the status
      and the proportions of CL induced by Leishmania major and L. tropica among CL
      suspected patients referred to the Center for Research and Training in Skin
      Diseases and Leprosy, (CRTSDL) during 2008 to 2011 are described. METHODS: CL
      patients with suspected lesions were clinically examined. History of trip to
      zoonotic CL and/or anthroponotic CL endemic areas and the characteristics of
      their lesion(s) were recorded. Diagnosis of the lesion was done using direct
      smear microscopy, culture and conventional polymerase chain reaction (PCR).
      RESULTS: A total of 404 (M = 256, F = 148) patients with 776 lesions were
      recruited and parasitologically examined. The results showed that 255 of the
      patients with 613 lesions; patients with lesion(s) induced by L. major=147 (M =
      63, 43%, F = 84, 57%) and lesion(s) induced by L. tropica=108 (M = 35, 32%, F =
      73, 68%). History of travel to endemic area was not always correlated with
      isolated Leishmania species. CONCLUSION: Although travel history to endemic area
      is an important factor to be considered for diagnosis, but parasitological
      confirmation is necessary initiation of treatment.

PMID- 24454438
TI  - Validation of PCR Assay for Identification of Sarcoptes scabiei var. hominis.
AB  - BACKGROUND: Infestation of the skin by the "itch mite" Sarcoptes scabiei var.
      hominis results in a contagious skin infection in humans called "scabies". By
      resolving morphology issues, the present study was designed to be acquainted with
      itch mite by molecular markers. METHODS: The mite samples were collected from
      scabies patients by visiting government hospitals of twin City, Pakistan. For
      successful molecular detection approach, preparation of Sarcoptes mite DNA by
      commercial DNA extraction kit method. Furthermore, two primers i.e. Sarms 15 F/R
      and 16S D1/D2 were used to amplify target sequence by using PCR. The amplified
      products were then separated by agarose gel, electrophoresis and analyzed after
      staining and visualizing in UV transilluminator. RESULTS: Analysis of PCR product
      showed one specific band of 178 bp with primer Sarms 15 F/R, while, with primer
      16S D1/D2 bands of 460 bp and 600 bp were observed on 2% agarose gel. The
      appearance of different band of 600 bp revealed that it might be due to
      heteroplasmy state present in the Pakistani Sarcoptes mites population.
      CONCLUSION: Current study adds validity to the claim that PCR is more accurate,
      specific and sensitive in the detection of the ectoparasites even in smallest
      amount.

PMID- 24454439
TI  - Development of 116 kDa Fraction for Detecting Experimental Toxoplasma gondii
      Infections in Mice.
AB  - BACKGROUND: Serological diagnosis of Toxoplasma gondii infection using crude
      antigens may not be more accurate. To increase the diagnostic potency of
      antigens, isolation of their immunogenic fractions could be useful. The current
      research adopted to obtain an affinity isolated fraction from RH strain using
      CNBr Sepharose 4B column coupled with infected mice sera helping in detection of
      IgM and IgG of toxoplasmosis due to RH strain and other strains. METHODS: The
      isolated fraction was characterized by SDS-PAGE. Moreover, the diagnostic potency
      of the fraction was assessed by indirect ELISA in mice experimentally infected
      with RH strain and two other local strains; one of sheep origin and the other of
      human origin. RESULTS: The fraction was found to be consisted of a single band of
      116 kDa compared with 17 bands ranged from 116 to 16 kDa associated with crude
      extract. The fraction proved potent diagnostic potentials of acute and chronic
      mice toxoplasmosis. Where it was detected both IgM and IgG antibodies as early as
      two days and as late as 2 months post experimental infection with any of the
      three strains. The level of detected IgM and IgG by RH fraction was higher in
      mice infected with RH strain than with local strains except IgM due to sheep
      strain parasite. CONCLUSIONS: The 116 kDa fraction of T. gondii tachyzoites can
      be considered as a candidate in improving of serodiagnosisof Toxoplasma
      infections.

PMID- 24454440
TI  - Protection Efficacy of Multivalent Egg Yolk Immunoglobulin against Eimeria
      tenella Infection in Chickens.
AB  - BACKGROUND: To control avian coccidiosis with drug-independent strategy
      effectively and safely, multivalent hyperimmune egg yolk immunoglobulin (IgY) was
      prepared and its ability to protect against Eimeria tenella infection was
      evaluated. METHODS: Hens were orally immunized with live oocysts of 5 species of
      Eimeria for six times, antibody titers in serum and yolk were monitored by
      indirect enzyme-linked immunosorbent assay. The specific IgY was isolated,
      purified and lyophilized. IgY powder was orally administrated as dietary
      supplement in newly hatched chicks at various dosages. Birds were orally
      challenged with 10000 sporulated oocysts of E. tenella at 10 days of age, weighed
      and killed at 8 days post challenge, and the protective effect was assessed.
      RESULTS: The averge yeid of IgY was 9.2 mg/ml yolk, the antibody titer of IgY
      reached to 1:163840 per mg with the purity up to 98%. Chickens fed IgY resulted
      in reduced mortality, increased body weight gain (BWG), reduced oocyst shedding,
      reduced caecal lesion score and increased anti-coccidial index. In terms of BWG
      and caecal lesion, IgY significantly enhanced the resistance of bird at >= 0.05%
      of IgY in the diet when compared with the challenged control group (P<0.05). No
      significant difference was observed at dosage >= 0.5% and 1.0% when BWG and
      caecal lesion were compared with the sodium salinomycin control group,
      respectively (P>0.05). CONCLUSION: Supplementing newly hatched chicks with
      Eimeria-specific IgY represents a promising strategy to prevent avian
      coccidiosis.

PMID- 24454442
TI  - Urinary schistosomiasis in urban and semi-urban communities in South-eastern
      Nigeria.
AB  - BACKGROUND: In view of the massive rural-to-urban migration in Nigeria,
      investigations on transmission of urinary schistosomiasis were carried out in
      urban and semi-urban communities in Nike Lake area of Enugu State, Nigeria.
      METHODS: Urine samples of school children were tested for micro-haematuria using
      reagent strips followed by microscopic examination for Schistosoma haematobium
      eggs. Water contact sites were also identified and sampled for snails. RESULTS:
      The overall prevalence of S. haematobium eggs in school children was 4.64%. The
      mean intensity of infection was 1.14 +/- 0.41 eggs/10ml urine. Males had
      insignificantly higher prevalence and intensity of S. haematobium infection than
      females. The youngest age group (4-7 years) had no infection. The prevalence of
      micro-haematuria (6.2%) was higher than that of microscopy, and this correlated
      positively with prevalence (r = 0.65, P < 0.01) and intensity (r = 0.50, P <
      0.01) of the infection. Potential intermediate host of human shistosome collected
      were: Bulinus globosus, B. senegalensis and Biomphalaria pfeifferi. However, only
      B. globosus shed cercariae of S. haematobium, with a snail infection rate of
      0.73%. Transmission was in the dry season coinciding with the drying of wells.
      CONCLUSION: The results revealed that urinary schistosomiasis is prevalent, and
      that B. globosus and not B. truncatus as previously reported is the main
      intermediate host of urinary schistosomiasis in this part of Enugu State.

PMID- 24454441
TI  - Endoparasites of stray dogs in mashhad, khorasan razavi province, northeast iran
      with special reference to zoonotic parasites.
AB  - BACKGROUND: To find out different species of helminthes and blood/tissue
      protozoan parasites of stray dogs and their potential role for transmission of
      zoonotic species to human in Mashhad, Khorasan Razavi Province, northeast Iran,
      during 2008-2009. METHODS: Totally, 100 stray dogs were selected among Mashhad
      municipal collection from different sites of the city. Internal organs were
      examined for any parasites. Helminthes were identified based on morphological
      characteristics. Smears prepared from peripheral blood as well as liver, spleen
      and any skin lesion were stained by Giemsa and examined microscopically. Samples
      obtained from spleen were aseptically cultured in three culture media including
      NNN, Schneider's Drosophila (HIMEDIA) and RPMI1640 (GIBCO) for isolation of
      Leishmania spp. The titer of anti-Leishmania and anti-Toxoplasma antibodies were
      measured by direct agglutination test (DAT) and indirect fluorescent antibody
      test (IFAT), respectively. RESULTS: 84% of dogs were infected at least with one
      species of intestinal helminthes. The species of parasites and rate of infection
      were as follows: Taenia hydatigena (61%), Dipylidium caninum (46%), Mesocestoides
      lineatus (19%), Echinococcus granulosus (10%), Toxascaris leonina (53%) and
      Toxocara canis (7%). Anti-Leishmania antibodies were detected by DAT in 8 dogs
      (8%) at 1:320 titers and higher. Forty seven dogs (47%) showed anti-Toxoplasma
      titer at 1:10 and 17 (17%) showed titer of >=1:100. No blood parasites were found
      in prepared blood smears. CONCLUSION: The high rate of parasitic infection and
      presence of zoonotic species especially E. granulosus and T. canis emphasizes the
      risk of diseases spread in urban areas by stray dogs.

PMID- 24454443
TI  - Effect of zinc on humoral and cell-mediated immunity of broilers vaccinated
      against coccidiosis.
AB  - BACKGROUND: The aim of the present study was the comparison of humoral and cell
      mediated immunity in broilers fed with different levels of zinc during a
      coccidiosis challenge. METHODS: One hundred and forty-four one-day-old broiler
      chicks were used with three dietary zinc (40, 120 and 200 mg/kg). At 14 d of age,
      all birds were inoculated orally with 5*10(3) sporulated oocysts of E. Tenella.
      At 2, 22, 32, 42 days of age, the blood serums were tested for antibody titer
      against Newcastle disease vaccine, using the standard HI test. On day 42 the sum
      of nitrite and nitrate based on the reduction of nitrate to nitrite by cadmium
      and white blood cell count (WBC) using a hemocytometer were measured. RESULTS: At
      42 d, levels of 120 and 200 mg significantly (P< 0.05) increased the antibody
      titer in compare with the control. The peak response of CBH was observed at the
      level of 200 mg Zn/kg diet. Also both level of 120 and 200 mg Zn/kg diet
      increased WBC count and sum of nitrite and nitrate in serum compared with the
      control. CONCLUSION: The levels of 120 and 200 mg Zn/kg diet could be considered
      as a non-pharmacologic booster of immunity in broilers chicks infected with E.
      Tenella.

PMID- 24454444
TI  - First Report of Hartmannella keratitis in a Cosmetic Soft Contact Lens Wearer in
      Iran.
AB  - BACKGROUND: Poor hygiene will provide good condition for corneal infections by
      opportunistic free-living amoebae (FLA) in soft contact lens wearers. In the
      present study an amoebic keratitis due to Hartmannella has been recognized in a
      22-year-old girl with a history of improper soft contact lens use. She had
      unilateral keratitis on her left eye. Her clinical signs were eye pain, redness,
      blurred vision and photophobia. The round cysts of free-living amoebae were
      identified in non-nutrient agar medium by light microscopy. These cysts were
      suspected to be Hartmannella using morphological criteria. A PCR assay has been
      confirmed that the round cysts were belonged to H. vermiformis.

PMID- 24454445
TI  - Plagiorchis muris (Tanabe, 1922) in Rattus norvegicus in Iran.
AB  - Rats are capable to harbor various pathogens, among which certain species of
      zoonotic parasites are included. A long-term detection of parasite fauna of rats
      has sporadically been carried out in Iran. Abundance of these vertebrate pests is
      of great importance as regards public health issue. The present paper is focused
      on a digenean trematode Plagiorchis muris, obtained during a comprehensive study
      on rats over the decades in the country. Herein we describe this occurrence in a
      Rattus norvegicus in northern Tehran, with specific note on its morphological
      description. P. muris can infect human through consumption of infected marine
      food items, and has never been observed in Iran. 

PMID- 24454446
TI  - Redescription of the Lutztrema (Lutziella) microacetabularae Rohde, 1966
      trematode of the Family Dicrocoelidae (Looss, 1899).
AB  - BACKGROUND: A known species Lutztrema (Lutziella) microacetabularae Rhode, 1966
      is being described for the first time from Pakistan. This species is
      characterized by having body long and slender, oral sucker subterminal,
      acetabulum smaller than oral sucker lying in anterior third of the body, pharynx
      small, esophagus prominent which become gradually wider and bifurcates in to two
      rudimentary caeca. Testes symmetrical at the level of posterior margin of
      acetabulum separated by uterine coils, cirrus pouch median, pre-acetabular,
      genital opening some distance behind pharynx. Receptaculumsemin is behind ovary.
      Ovary submedian, post-testicular, Laurer's canal present. Vitellaria lateral from
      the level of testes to a short distance behind middle of the body. Uterus
      occupies most of the hind body, eggs small, oval, numerous. It is being reported
      from the rat (Rattusrattus L.) from Swat.

PMID- 24454447
TI  - Two New Trematodes of Family Acanthocolpidae Luhe, 1906 From Marine Fish
      Leiognathus daura (Cuvier) from the Coast of Puri, Orissa, India.
AB  - BACKGROUND: Genus Acanthocolpus (Trematoda: Acanthocolpiidae) is one of the most
      important zoonotic digenean with wide geographic distribution in the world. The
      purpose of the present study was to describe morphological and morphometrical
      characteristics of Acanthocolpus species, currently prevalent in marine fish
      fauna of Puri coast, Orissa, India. METHODS: Gastro-intestinal organs of
      Leiognathus daura (Cuvier) in Puri coast, Orissa, India, were examined for
      infectivity with digenean trematode species. For examination and measurements of
      helminthes, acetoalum carmine staining was performed, followed by camera Lucida
      drawings of morphological characters and measurements of morphometrical criteria
      with a calibrated microscope. Using valid trematode systematic keys, almost all
      the parasites were identified at the level of species. RESULTS: Overall, 36
      marine fishes were found infected with at least one species of Acanthocolpus.
      Considering morphological characteristics of Acanthocolpus, two species were
      identified as new species including Acanthocolpus durghai sp.nov. and
      Acanthocolpus amrawatai sp.nov. CONCLUSION: During the survey of helminth
      parasites, collected six different species of the genus Acanthocolpus, out of
      these two are new species, another is redescribed to show certain variation, the
      new parasite was obtain from the intestine of marine fish Leiognathus daura
      (Cuvier).

PMID- 24454448
TI  - The effect of different suture removal time intervals on surgical wound healing.
AB  - INTRODUCTION: This study was carried out to compare the effect of different
      suture removal time on surgical wound healing. MATERIALS AND METHODS: Twenty-one
      male albino rabbits were used. Under general and local anesthesia a
      moucoperiosteal rectangular flap was raised in each animal and then repositioned
      and sutured. The animals were randomly divided into three experimental groups of
      seven animals each. In group I and II the sutures were removed after 3 and 5 days
      respectively and were followed up for 7 and 14 days after surgery. In group III
      the sutures were removed after 7 days and were followed up for 14 days after
      surgery. Tissue reactions were observed and recorded using inflammation and
      gingival indexes at 7 and 14 days after surgery in all three groups. Inflammation
      and gingival indexes were analyzed by Kurskal Wallis, Firedman and Wilcoxone
      tests. RESULTS: Results showed that inflammation index was significantly
      different with two other groups at the day 7 after surgery (P<0.008). Gingival
      index in group II was significantly different from two other groups at the day 14
      (P<0.028); however, there was no significant difference between group II and III
      at the same interval. CONCLUSION: Based on result of this study, 5 days was
      recognized to the best time interval for suture removal in comparison with two
      other time intervals.

PMID- 24454449
TI  - The Cellular Behavior and SEM Evaluation of ProRoot and Root MTAs on Fibroblast
      L929.
AB  - INTRODUCTION: Mineral trioxide aggregate is being widely used for root end
      filling, pulp capping, perforation repair, and other endodontic procedures.
      Recently, a material similar to ProRoot mineral trioxide aggregate (PMTA) was
      developed in Iran named Root mineral trioxide aggregate (RMTA) with the claim of
      having the exact result of original MTA. The purpose of this study was to compare
      the amount of cell cytotoxicity of RMTA with PMTA at three different time periods
      using scanning electron microscopy (SEM) as well as the amount of cell viability
      at the above mentioned period. MATERIALS AND METHODS: Three culture plates in
      each group were packed with a homogenous layer of PMTA and RMTA prepared
      according to manufacturers instruction. A plate of media without any material was
      used as control in each group. The material set for 72 h in CO2 incubator and
      2x10 of fibroblast L929 was added to each plate. SEM evaluation with x800-3000
      magnification and cell viability counting using trepan blue counting method were
      done after 48, 72, and 168 hours. RESULTS: There was no significant difference
      between cell viability of PMTA and RMTA, although the amount of cells remained
      viable in PMTA group was higher at 48 and 168 hours while for RMTA, it was higher
      after 72 hours. The SEM evaluation showed that PMTA compared with RMTA has less
      porosity, but relatively similar amount of cell coverage was detected for both
      materials after 168 hours. CONCLUSION: ProRoot and Root MTAs showed comparative
      biocompatibility while evaluated in vitro. The results suggest that RMTA can be
      used as an alternative for PMTA in clinical trials.

PMID- 24454450
TI  - Bacterial leakage of mineral trioxide aggregates and portland cement.
AB  - INTRODUCTION: The purpose of this study was to compare the ability of ProRoot
      mineral trioxide aggregate (PMTA) and Root mineral trioxide aggregate (RMTA) as
      root-end filling materials, and Portland cement (PC) to prevent bacterial leakage
      through filled root end cavities. MATERIALS AND METHODS: Fifty-one extracted
      human single rooted teeth were cleaned and shaped using a step back technique.
      The root-ends were resected and a 4 mm deep root-end preparation was made with
      fissure bur. The teeth were randomly divided into three experimental groups
      (n=15) and a further six teeth served as controls. Three root-end cavities were
      filled with gutta-percha without a root canal sealer (positive control) and three
      remaining were filled with sticky wax, covered with two layers of nail polish
      (negative control). Root-end cavities in each experimental group were filled with
      PMTA, RMTA or PC. After attaching the teeth to plastic caps of 9 ml vials, the
      teeth and the caps were sterilized using Gamma ray. Then the caps with teeth were
      placed on the vials containing Phenol Red Lactose broth. A tenth of microliter of
      Tripticase Soy broth containing Staphylococcus Epidermidis (SE) was placed into
      the root canals of the teeth. Every 48 hours inoculation of 0.1 ml of the SE
      broth culture into each root canal was performed. RESULTS: All positive controls
      leaked within 3 days, none of the negative controls leaked. Bacterial leakage
      occurred in 33% of samples in the PMTA group and in 40% of samples in RMTA and PC
      groups. The results indicated no statistical difference between three test
      materials after 35 days. CONCLUSION: It was concluded that PMTA, RMTA and PC
      demonstrated a similar ability to seal root end cavities.

PMID- 24454451
TI  - Clinical and Radiographic Evaluation of Procedural Accidents and Errors during
      Root Canal Therapy.
AB  - INTRODUCTION: Root canal therapy (RCT)_like other dental practices_ can be
      accompanied with some accidents or unpredictable conditions that are called
      "procedural accidents". Having the knowledge about these accidents and their
      etiology is essential to have RCT completion and to prevent the repeat of these
      accidents. This study was designed to evaluate accidents occurring during RCT in
      patients referred to endodontic department of Shaheed Beheshti dental school
      during 2002. MATERIALS AND METHODS: This study was conducted via descriptive
      method. Data were collected from observation, clinical examination and oral
      radiographs, and were recorded in questionnaires, 150 cases from the patients
      referred to endodontic department were selected randomly and different observed
      RCT errors were analyzed by SPSS software. The Chi-square and Fisher exact tests
      were used for analysis. RESULTS: The study showed that 101 patients (67.3%) had
      one type of RCT errors, and remaining (32.7%) were error free. From the errors
      studied the most prevalent were "void" which was observed in 41 patients (27.3%),
      and "ledge" in 39 patients (26%) respectively. The prevalence of other accidents
      were underfilling in 35 patients (23.3%), poor shaping in 30 patients (20%),
      overfilling in 23 patients (15.3%), transportation in 13 patients (8.7%), zipping
      in 3 patients (2%), gouging in 1 patients (0.7%), and strip perforation in 1
      patients (0.7%), while no case of broken instruments, vertical fracture,
      furcation and cervical perforation was observed. CONCLUSION: The most prevalent
      errors were found in instrumentation and obturation steps, therefore more care
      and attention must be paid to instructor observation and the education of these
      stages.

PMID- 24454452
TI  - Sealing ability of three commercial mineral trioxide aggregates and an
      experimental root-end filling material.
AB  - INTRODUCTION: The purpose of this study was to compare the sealability of three
      different commercial types of mineral trioxide aggregate (MTA) and calcium
      enrichment mixture (CEM) cement as an experimental root-end filling material.
      MATERIALS AND METHODS: Forty-six single rooted teeth were cleaned, shaped, and
      obturated. The apical 3 mm of each root was resected and root-end cavities with 3
      mm depth were prepared. The samples were randomly divided into 4 experimental
      groups comprised of 10 roots each. The cavities were filled with CEM cement and
      MTAs. Six roots were used as positive and negative controls. Samples were
      prepared and then immersed in 1% methylene blue dye for 3 days. Roots were split
      longitudinally and examined under stereomicroscope. RESULTS: Positive and
      negative controls responded as expected. CEM cement showed the least mean dye
      penetration value. ANOVA revealed no statistically significant differences among
      experimental groups. CONCLUSION: It was concluded that the experimental CEM
      cement exhibited similar sealing property as commercial types of MTA.

PMID- 24454453
TI  - An Evaluation of MTA Cements as Coronal Barrier.
AB  - INTRODUCTION: Coronal leakage seems to play an important role in the failure of
      endodontic treatment. A double seal over root canal filling has been suggested as
      a means of improving the coronal seal. Several restorative materials have been
      used in an attempt to produce a coronal barrier. The purpose of this study was to
      assess gray-coloured mineral trioxide aggregate (GMTA), white-coloured mineral
      trioxide aggregate MTA (WMTA), and Principle (a resin-modified glass ionomer) as
      coronal barriers to bacterial leakage. MATERIALS AND METHODS: Fifty-one human
      anterior teeth were cleaned and obturated with gutta-percha and sealer. In group
      1, teeth received a 3 mm barrier of GMTA. In groups 2 and 3, samples received
      WMTA and Principle, respectively. Obturated teeth without barrier were used as
      positive control and obturated teeth covered with epoxy resin were used as
      negative control. A leakage model utilizing Enterococcus faecalis used for the
      evaluation. Leakage was recorded when turbidity was observed. RESULTS: All
      controls behaved as expected. Three samples in group 1, three samples in group 2,
      and four samples leaked in group 3. There was no statistically significant
      difference in leakage between GMTA and WMTA or between GMTA and Principle.
      CONCLUSION: It seems that GMTA, WMTA and Principle can be recommended as a
      coronal barrier for up to 90 days.

PMID- 24454454
TI  - Comparison of cytotoxicity of three dentin bonding systems with two thicknesses
      of dentin barrier on l929 cell line.
AB  - INTRODUCTION: Along with introduction of dentin bonding agents (DBA), their
      clinical use as lining materials is increasing rapidly. Since remaining dentinal
      thickness (RDT) has always been a concern for cytopathic effect of restorative
      materials, its effect on reduction of cytotoxicity of these materials especially
      DBAs is critical. The purpose of this study was to evaluate and compare the
      cytotoxicity of three dentin bonding systems, belonged to the 4(th), 5(th) and
      6(th) generation of DBAs on L929 cell line. MATERIALS AND METHODS: Thirty human
      premolar teeth were included. Class I cavity preparations were prepared on
      occlusal surfaces. After crown separation, a flat dentinal surface was provided
      and RDT (remaining dentinal thickness) was adjusted at 0.5 and 1.5 mm. Then,
      cavities were treated in three groups with experimental DBAs: Group 1: Scotchbond
      multipurpose, Group 2: Excite, Group 3: AdheSE. Blue inlay wax sealed the
      cavities. Crowns were immersed in culture medium for 24 hours and the
      cytotoxicity of the resultant toxic medium was measured quantitatively with MTT
      assay in 4 serial dilutions. Data were analyzed with ANOVA and Tukey's test at
      95% significance level. RESULTS: MTT assay determined that only in neat dilution
      of 0.5 mm RDT, cell changes were significantly different from control. Besides,
      no significant differences were found between the three experimental DBAs
      regarding cytotoxic effect on L929 cell line. CONCLUSION: Considering the
      limitations of an in vitro study, if the RDT is less than 0.5 mm in vivo,
      regardless of the type of DBA, destructive cellular changes in pulp tissue can be
      expected.

PMID- 24454455
TI  - Endodontic treatment of a taurodontism tooth: report of a case.
AB  - Taurodontism is a rare dental anomaly in which the involved tooth has an enlarged
      and elongated body and pulp chamber with apical displacement of the pulpal floor.
      Endodontic treatment of these teeth is challenging, because it is hard to
      identify the number of root canals. In this article a case of bilateral
      involvement of maxillary first molars is presented. Endodontic treatment of right
      maxillary first molar with taurodontism was indicated due to irreversible
      pulpitis. This article describes the procedures of root canal therapy. 

PMID- 24454456
TI  - Distribution of BRCA1 and BRCA2 Mutations in Asian Patients with Breast Cancer.
AB  - Breast cancer is the most prevalent cancer in Asian females, and the incidence of
      breast cancer has been increasing in Asia. Because Asian patients develop breast
      cancer at a younger age than their Caucasian counterparts, the contributions of
      BRCA1 and BRCA2 (BRCA1/2) mutations in Asians are expected to be different than
      in Caucasians. The prevalence of BRCA1/2 mutations in the Asian population varies
      among countries and studies. Most Asian studies have reported more frequent
      mutations in BRCA2 than in BRCA1, with the exception of studies from India and
      Pakistan. In addition, the contribution of large genomic rearrangements of
      BRCA1/2 genes is relatively small in Asian populations in comparison to other
      ethnic populations. Various statistical models for the prediction of BRCA1/2
      mutations have underestimated the risk of having these genetic mutations in
      Asians, especially in predicting BRCA2 gene mutation. Until recently, BRCA1/2
      mutation analyses in Asia were mostly conducted by independent single
      institutions with different patient selection criteria and using various
      genotyping methods. However, a couple of Asian groups have initiated nationwide
      studies collecting BRCA1/2 mutational data. These national collaborative studies
      will help a comprehensive understanding of the prevalence of BRCA1/2 mutations in
      the Asian population. 

PMID- 24454457
TI  - Case-control study on the fibroblast growth factor receptor 2 gene polymorphisms
      associated with breast cancer in chinese han women.
AB  - PURPOSE: Genetic variation in fibroblast growth factor receptor 2 (FGFR2) is a
      newly described risk factor for breast cancer. This study aimed to evaluate the
      association of four single nucleotide polymorphisms (SNPs) in FGFR2 with breast
      cancer in Han Chinese women. METHODS: Two hundred three women with breast cancer
      and 200 breast cancer-free age-matched controls were selected. Four SNPs
      (rs2981579, rs1219648, rs2420946, and rs2981582) and their haplotypes were
      analyzed to test for their association with breast cancer susceptibility. The
      presence of the four FGFR2 SNPs was determined by polymerase chain reaction
      restriction fragment length polymorphism analysis. RESULTS: A statistically
      significant difference was observed in the frequency of rs2981582 in the FGFR2
      gene (p<0.05) between case and control groups. In subjects stratified by
      menopausal status, rs2981582 TT, rs2420946 AA, and rs1219648 CC were
      significantly associated with the risk of breast cancer in postmenopausal
      subjects, but no significant associations between these four SNPs and the risk of
      breast cancer were identified in premenopausal subjects. Further, there was no
      significant association between hormone receptor status (estrogen receptor and
      progesterone receptor) and breast cancer risk. Six common (> 3%) haplotypes were
      identified. Three of these haplotypes, CGTC (odds ratio [OR], 0.613; 95%
      confidence interval [CI], 0.457-0.82; p=0.001), TGTC (OR, 6.561; 95% CI, 2.064
      20.854; p<0.001), and CATC (OR, 12.645; 95% CI, 1.742-91.799; p=0.001) were
      significantly associated with breast cancer risk. CONCLUSION: Our findings
      indicated that the SNP rs2981582 and haplotypes CGTC, TGTC, and CATC in FGFR2 may
      be associated with an increased risk of breast cancer in Han Chinese women.

PMID- 24454458
TI  - Social disparity in breast and ovarian cancer incidence in iran, 2003-2009: a
      time trend province-level study.
AB  - PURPOSE: This pioneering study aimed to investigate social disparities in breast
      cancer (BC) and ovarian cancer (OC) incidence rates among women across Iran's
      provinces from 2003 to 2009. METHODS: Provincial level population distribution
      data pertaining to women were obtained from the Statistical Centre of Iran. Age
      standardized incidence rates of BC and OC were gathered from the National Cancer
      Registry. Human Development Index was used as the provinces' social rank (SR),
      and rate ratio and Kunst and Mackenbach relative index of inequality were used to
      assess social disparities. Annual percentage change (APC) was calculated using
      joinpoint regression, and Spearman rank correlation was used to examine the
      association between APC and SR. RESULTS: It was found that over the study period,
      annual incidence rates rose by 11.6% and 9.7% for BC and OC, respectively. Social
      disparities were substantial and stable in favor of provinces with lower SR in
      Iran, and were more profound for BC than OC. Correlations between APC and SR were
      small and nonsignificant for both BC and OC. CONCLUSION: The results showed that
      both BC and OC incidence increased in Iran during 2003 to 2009. There were
      positive associations between BC and OC incidence rates and the provinces' SR.
      This study's recommendations provide valuable information for health resource
      allocation pertaining to BC and OC control programs across provinces in Iran.

PMID- 24454459
TI  - Reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in
      breast cancer patients.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) is an accurate and effective means of
      axillary nodal staging in early breast cancer. However its indication after
      neoadjuvant chemotherapy (NAC) is under constant debate. The present study
      evaluates the reliability of SLNB in assessing axillary nodal status after NAC.
      METHODS: Data from 281 patients who had received NAC and subsequent SLNB were
      reviewed. The identification and false negative rates of SLNB were determined and
      the clinicopathologic factors associated with false negative results were
      investigated using univariate analysis. RESULTS: The identification rate of SLNB
      after NAC was 93.6% and the false negative rate was 10.4%. Hormone receptor
      status, especially progesterone receptor positivity, was significantly associated
      with false negative results. The accuracy of intraoperative frozen section
      examination of sentinel lymph nodes was 91.2%. CONCLUSION: The identification
      rate of SLNB and the accuracy of intraoperative frozen section examination after
      NAC are comparable to the results without NAC in patients with early breast
      cancer. However considering the high false negative rates, general application of
      SLNB after NAC should be avoided. Patients with progesterone-positive tumors and
      non-triple-negative breast cancers may be a select group of patients in whom SLNB
      can be employed safely after NAC, but further studies are necessary.

PMID- 24454460
TI  - Effect Modification of Hormonal Therapy by p53 Status in Invasive Breast Cancer.
AB  - PURPOSE: We aimed to confirm the prognostic and predictive value of p53
      expression, particularly in invasive breast cancer patients, according to
      immunohistochemical hormone receptor (HR) and human epidermal growth factor
      receptor 2 (HER2) status. METHODS: Immunohistochemical data for p53, estrogen
      receptor, progesterone receptor, and HER2 expression from a total of 15,598
      patients were retrospectively retrieved from the web-based database of the Korean
      Breast Cancer Society. Overall survival (OS) and breast cancer-specific survival
      (BCSS) were calculated and compared using the Kaplan-Meier method and log-rank
      test, respectively. Multivariate analyses were performed using a stratified Cox
      proportional hazard regression model. A model evaluating interactions between p53
      expression and both hormonal therapy and chemotherapy was used to determine the
      treatment benefit from both modalities. RESULTS: The prognostic value of p53 for
      OS and BCSS was most significant in the HR+/HER2- subgroup, with hazard ratios of
      1.44 (95% confidence interval [CI], 1.08-1.93) and 1.47 (95% CI, 1.09-1.99),
      respectively. The p53 overexpression hazard ratios were of borderline
      significance for the HR+/HER2+ subgroup and were not significant for the HR
      /HER2+ and HR-/HER2- subgroups. The model with interaction terms revealed that
      hormonal therapy significantly interacts with p53 status (p=0.002 and p=0.007 for
      OS and BCSS, respectively), suggesting an insignificant prognostic value for p53
      status (p=0.268 and p=0.296 for OS and BCSS, respectively). An interaction
      between chemotherapy and p53 status was not found in this model. CONCLUSION: p53
      overexpression has independent prognostic value, particularly in cases of
      HR+/HER2- invasive breast cancer, which may be due to effect modification of
      hormonal therapy dependent on p53 status.

PMID- 24454461
TI  - Expression of Immunohistochemical Markers before and after Neoadjuvant
      Chemotherapy in Breast Carcinoma, and Their Use as Predictors of Response.
AB  - PURPOSE: For patients with breast carcinoma, immunohistochemical markers are
      important factors in determining the breast cancer subtype and for establishing a
      therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However,
      it is not clear whether the expression of certain markers changes after NACT.
      METHODS: We assessed estrogen receptor (ER), progesterone receptor (PR), human
      epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in
      specimens from 345 breast cancer cases before and after NACT. We analyzed the
      association between response to NACT and the expression of the markers in pre
      NACT specimens. We also compared the expression between pre- and post-NACT
      specimens. RESULTS: ER and PR expression was negatively associated with
      pathological complete response (pCR). HER2 was associated with pCR in all cases,
      but the association was lost when the cases were subdivided according to hormone
      receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller
      than that of cases with residual disease. HER2-enriched and triple-negative
      breast cancers were more likely to achieve pCR than luminal A type cancers. PR
      expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67
      index was also demonstrated in hormone receptor positive and HER2-enriched
      subtypes, but no similar tendency was observed in the triple-negative subtype.
      CONCLUSION: A patient with breast cancer scheduled for NACT should be assessed
      for the breast cancer subtype, as this will influence the treatment plans for the
      patient. The expression of PR and Ki-67 after NACT should be interpreted
      carefully because NACT tends to reduce the expression of these molecules.

PMID- 24454462
TI  - Tubular carcinoma of the breast: clinicopathologic features and survival outcome
      compared with ductal carcinoma in situ.
AB  - PURPOSE: Tubular carcinoma (TC) of the breast is an uncommon histological subtype
      of invasive breast cancer with an excellent prognosis compared with standard
      invasive ductal carcinoma. Recent studies suggested a possible precursor role for
      low grade ductal carcinoma in situ (DCIS) in the development of TC. The goal of
      this analysis was to understand the clinicopathologic features and outcomes of TC
      by comparing TC with DCIS. METHODS: A retrospective review identified 70 patients
      with TC and 1,106 patients with DCIS between 1995 and 2011. Student t-test and
      Fisher exact test were used to compare the clinicopathologic characteristics of
      TC patients with those of DCIS patients. The Kaplan-Meier method and Cox
      regression analysis were used to determine disease-free survival (DFS) rates.
      RESULTS: Compared to DCIS, TC exhibited favorable clinicopathologic
      characteristics such as a lower nuclear grade (92.3%), higher expression of
      hormonal receptors (estrogen receptor-positive, 92.9%; progesterone receptor
      positive, 87.0%), and less frequent overexpression of human epidermal growth
      receptor 2 (12.9%). DFS did not differ significantly between the TC and DCIS
      groups (5-year DFS, 100% vs. 96.7%; 10-year DFS, 92.3% vs. 93.3%; p=0.324), and
      cancer-specific deaths were not noted in either group. However, axillary lymph
      node involvement was observed in six (8.6%) of the 70 patients with TC. Three of
      these patients had small tumors (<=1 cm). CONCLUSION: In our study cohort, TC was
      associated with an excellent prognosis and a low rate of lymph node metastasis.
      However, lymph nodes metastases were found even in patients with small tumors
      (<=1 cm). Axillary staging must be considered for all patients with TC of the
      breast.

PMID- 24454463
TI  - Survival outcomes of different treatment methods for the ipsilateral breast of
      occult breast cancer patients with axillary lymph node metastasis: a single
      center experience.
AB  - PURPOSE: This study compared the survival outcomes of different treatment methods
      for the ipsilateral breast of occult breast cancer (OBC) patients with axillary
      lymph node metastasis. METHODS: A retrospective study was conducted in which
      forty OBC patients with axillary lymph node metastasis were identified out of
      15,029 patients who had been diagnosed with a primary breast cancer at between
      1992 and 2010. The patients were categorized into three treatment groups based on
      ipsilateral breast management: breast-conserving surgery (BCS) (n=17), mastectomy
      (n=12), and nonsurgical intervention with or without radiation therapy (No
      surgery with or without radiation therapy [No Op+/-RT]) (n=11). All patients
      underwent axillary lymph node dissection. Cases were evaluated based on treatment
      and potential prognostic factors with respect to overall survival (OS) and
      disease-free survival (DFS). RESULTS: During the follow-up period (median follow
      up of 71.5 months), the overall OS and DFS were 76.9% and 74.9%, respectively.
      The 5-year treatment-specific OS was 72.0% for the BCS group, 74.0% for the
      mastectomy group, and 87.5% for the No Op+/-RT group (log-rank p=0.49). The 5
      year DFS was 70.6% for the BCS group, 66.7% for the mastectomy group, and 90.9%
      for the No Op+/-RT group (log-rank p=0.36). Recurrence rates for the BCS and No
      Op+/-RT groups were 5.9% and 18.2%, respectively. Histologic grade and lymph node
      status were inversely correlated with DFS (log-rank p=0.04 and p<0.01,
      respectively). CONCLUSION: There was no difference in survival outcomes between
      the three treatment methods for the ipsilateral breast (mastectomy, BCS, and No
      Op+/-RT) of OBC patients with axillary lymph node metastasis. A large-scale
      multicenter study is needed to validate the results from this small retrospective
      study.

PMID- 24454464
TI  - Comparison of the characteristics of medullary breast carcinoma and invasive
      ductal carcinoma.
AB  - PURPOSE: Medullary breast carcinomas (MBC) have been known to represent a rare
      breast cancer subtype associated with a more favorable prognosis than invasive
      ductal carcinomas (IDC). The purpose of this study was to compare the
      clinicopathologic characteristics and outcomes of MBC with those of IDC. METHODS:
      We retrospectively reviewed medical records of patients with invasive breast
      cancer who were managed surgically from August 1995 to June 2010. RESULTS: Fifty
      two patients were identified with MBC and 5,716 patients were identified with
      IDC. The clinicopathologic features, disease-free survival (DFS), and overall
      survival (OS) of patients with MBC were compared with those of patients with IDC.
      The MBC group presented at a younger age (p=0.005) and had a significant
      association with a higher histological grade (p=0.003) and nuclear grade
      (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone
      receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node
      metastasis was rare (p<0.001). The DFS and OS did not differ significantly
      between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4%
      vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS
      and OS were nuclear grade, histological grade, tumor size, lymph node metastasis,
      estrogen receptor status, progesterone receptor status, and human epidermal
      growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS
      and OS were not significantly different between IDC and MBC according to
      histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12
      6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77,
      p=0.692). CONCLUSION: Although MBC has specific clinicopathologic features, its
      prognosis does not differ from IDC and is determined by prognostic factors such
      as tumor size and lymph node metastasis. Therefore, patients with MBC also
      require the same intensive treatment provided for IDC.

PMID- 24454465
TI  - Synergistic interactions with a high intraoperative expander fill volume increase
      the risk for mastectomy flap necrosis.
AB  - PURPOSE: Prosthetic-based breast reconstruction is performed with increasing
      frequency in the United States. Major mastectomy skin flap necrosis is a
      significant complication with outcomes ranging from poor aesthetic appearance to
      reconstructive failure. The present study aimed to explore the interactions
      between intraoperative fill and other risk factors on the incidence of flap
      necrosis in patients undergoing mastectomy with immediate expander/implant-based
      reconstruction. METHODS: A retrospective review of 966 consecutive patients
      (1,409 breasts) who underwent skin or nipple sparing mastectomy with immediate
      tissue expander reconstruction at a single institution was conducted. Age, body
      mass index, hypertension, smoking status, premastectomy and postmastectomy
      radiation, acellular dermal matrix use, and application of the tumescent
      mastectomy technique were analyzed as potential predictors of flap necrosis both
      independently and as synergistic variables with high intraoperative fill. The
      following three measures of interaction were calculated: relative excess risk due
      to interaction, attributable proportion of risk due to interaction, and synergy
      index (SI). RESULTS: Intraoperative tissue expander fill volume was high (>=66.7%
      of the maximum volume) in 40.9% (576 of 1,409 breasts) of cases. The unadjusted
      flap necrosis rate was greater in the high intraoperative fill cohort than in the
      low fill cohort (10.4% vs. 7.1%, p=0.027). Multivariate logistic regression did
      not identify high intraoperative fill volume as an independent risk factor for
      flap necrosis (odds ratio 1.442, 95% confidence interval 0.973-2.137, p=0.068).
      However, four risk factors were identified that interacted significantly with
      intraoperative fill volume, namely tumescence, age, hypertension, and obesity.
      The SI, or the departure from additive risks, was largest for tumescence (SI,
      25.3), followed by hypertension (SI, 2.39), obesity (SI, 2.28), and age older
      than 50 years (SI, 1.17). CONCLUSION: In the postmastectomy, hypovascular milieu,
      multiple risk factors decreasing flap perfusion interact with high intraoperative
      fill volume to cross a threshold and synergistically increase the risk of flap
      necrosis.

PMID- 24454466
TI  - Invasive breast carcinoma arising in microglandular adenosis: two case reports.
AB  - Microglandular adenosis (MGA) is a rare benign disease that shows an infiltrative
      growth pattern of small glands, and it may progress to include atypia and
      carcinoma. Here we report two cases of breast carcinoma arising in MGA. Case 1
      was a 44-year-old woman with a previous history of ductal carcinoma in situ in
      her right breast. During a follow-up, a 1.8 cm mass-like lesion was found in her
      left breast. An excisional biopsy suggested that the lesion was breast carcinoma.
      Case 2 was a 57-year-old woman with a 2.9 cm mass in her right breast. A core
      needle biopsy of the lesion suggested invasive carcinoma. Both patients underwent
      modified radical mastectomy with sentinel lymph node biopsy. Both tumors lacked a
      myoepithelial cell layer and stained positively for S-100, lysozyme, and alpha1
      antitrypsin, which is typical of MGA. Both cases showed invasive carcinoma
      arising in MGA. 

PMID- 24454467
TI  - Expander/Implant breast reconstruction after reconstruction using an extended
      cutaneous thoracoabdominal flap: a case report.
AB  - Many flaps have been described and are being used in the reconstruction of
      extensive tissue defects in the thoracic wall. The extended cutaneous
      thoracoabdominal flap, described in 2006, is an excellent option for chest wall
      reconstruction in patients with advanced breast cancer, being associated with a
      low morbidity rate and good functional results. The main disadvantage of this
      technique is the poor cosmetic outcome and the complete absence of a breast
      crease. We present the first case of a two-stage heterologous breast
      reconstruction after reconstruction using an extended cutaneous thoracoabdominal
      flap. 

PMID- 24454468
TI  - Random synchronous malignancy in male breast: a case report.
AB  - We report here a case of a random synchronous male breast malignancy in a patient
      with a known base of tongue malignancy that was incidentally detected on a whole
      body 18-fluorine deoxyglucose positron emission tomography and computed
      tomography ((18)F-FDG PET/CT). Patient was referred to us for PET/CT staging and
      radiotherapy planning for a poorly differentiated squamous cell carcinoma of base
      of tongue. Histopathologically, the incidentally detected breast lesion was
      proven to be an invasive ductal carcinoma. (18)F-FDG PET/CT being a whole body
      imaging modality is known to detect a considerable number of synchronous
      primaries. Synchronous malignancies in the head and neck area and the upper
      aerodigestive tract are well established. However, synchronous malignancy in male
      breast is reportedly uncommon. Our case is unique for the fact that a random
      synchronous dual malignancy of base of tongue and breast in a male patient was
      detected during a whole body (18)F-FDG PET/CT imaging. 

PMID- 24454469
TI  - Original approach for automated quantification of antinuclear autoantibodies by
      indirect immunofluorescence.
AB  - INTRODUCTION: Indirect immunofluorescence (IIF) is the gold standard method for
      the detection of antinuclear antibodies (ANA) which are essential markers for the
      diagnosis of systemic autoimmune rheumatic diseases. For the discrimination of
      positive and negative samples, we propose here an original approach named
      Immunofluorescence for Computed Antinuclear antibody Rational Evaluation (ICARE)
      based on the calculation of a fluorescence index (FI). METHODS: We made
      comparison between FI and visual evaluations on 237 consecutive samples and on a
      cohort of 25 patients with SLE. RESULTS: We obtained very good technical
      performance of FI (95% sensitivity, 98% specificity, and a kappa of 0.92), even
      in a subgroup of weakly positive samples. A significant correlation between
      quantification of FI and IIF ANA titers was found (Spearman's rho = 0.80, P <
      0.0001). Clinical performance of ICARE was validated on a cohort of patients with
      SLE corroborating the fact that FI could represent an attractive alternative for
      the evaluation of antibody titer. CONCLUSION: Our results represent a major step
      for automated quantification of IIF ANA, opening attractive perspectives such as
      rapid sample screening and laboratory standardization.

PMID- 24454470
TI  - Activation of dendritic cells by the novel Toll-like receptor 3 agonist RGC100.
AB  - Toll-like receptor (TLR) 3 agonists emerged as attractive candidates for
      vaccination strategies against tumors and pathogens. An important mechanism of
      action of such agonists is based on the activation of TLR3-expressing dendritic
      cells (DCs), which display a unique capacity to induce and stimulate T-cell
      responses. In this context, it has been demonstrated that targeting of TLR3 by
      double-stranded RNA such as poly(I:C) results in potent activation of DCs. Major
      disadvantages of poly(I:C) comprise its undefined chemical structure and very
      poor homogeneity, with subsequent unpredictable pharmacokinetics and high
      toxicity. In the present study, we evaluated the physicochemical properties and
      biological activity of the novel TLR3 agonist RGC100. RGC100 has a defined
      chemical structure, with a defined length (100 bp) and molecular weight (64.9
      KDa) and a good solubility. RGC100 is stable in serum and activates myeloid DCs
      through TLR3 targeting, as evidenced by gene silencing experiments. Activation of
      mouse and human myeloid CD1c(+) DCs by RGC100 leads to secretion of several
      proinflammatory cytokines. In addition, RGC100 improves the ability of CD1c(+)
      DCs to stimulate T-cell proliferation. Due to its physicochemical properties and
      its immunostimulatory properties, RGC100 may represent a promising adjuvant for
      prophylactic and therapeutic vaccination strategies.

PMID- 24454471
TI  - Prolactin levels correlate with abnormal B cell maturation in MRL and MRL/lpr
      mouse models of systemic lupus erythematosus-like disease.
AB  - Prolactin (PRL) plays an important role in modulating the immune response. In B
      cells, PRL enhances antibody production, including antibodies with self
      specificity. In this study, our aims were to determine the level of PRL receptor
      expression during bone-marrow B-cell development and to assess whether the
      presence of high PRL serum concentrations influences absolute numbers of
      developing populations and disease outcome in lupus-prone murine models. We
      observed that the PRL-receptor is expressed in early bone-marrow B-cell; the
      expression in lupus-prone mice, which had the highest level of expression in pro
      B cells and immature cells, differed from that in wild-type mice. These
      expression levels did not significantly change in response to hyperprolactinemia;
      however, populations of pro-B and immature cells from lupus-prone strains showed
      a decrease in the absolute numbers of cells with high PRL-receptor expression in
      response to PRL. Because immature self-reactive B cells are constantly being
      eliminated, we assessed the expression of survival factor BIRC5, which is more
      highly expressed in both pro-B and immature B-cells in response to PRL and
      correlates with the onset of disease. These results identify an important role of
      PRL in the early stages of the B-cell maturation process: PRL may promote the
      survival of self-reactive clones. 

PMID- 24454472
TI  - Immunomorphologic manifestations in mice liver infected with influenza A/H5N1,
      A/goose/Krasnoozerskoye/627/05 strain.
AB  - Highly pathogenic avian influenza H5N1 (HPAI H5N1) viruses can infect mammals,
      including humans, causing severe systemic disease with the inhibition of the
      immune system and a high mortality rate. In conditions of lymphoid tissue
      depletion, the liver plays an important role in host defence against viruses. The
      changes in mice liver infected with HPAI H5N1 virus
      A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the
      virus persistence in the liver leads to the expression of proinflammatory
      cytokines (TNF- alpha , IL-6) and intracellular proteases (lysozyme, cathepsin D,
      and myeloperoxidase) by Kupffer cells. Defective antiviral response exacerbates
      destructive processes in the liver accelerating the development of liver failure.

PMID- 24454473
TI  - PADI4 haplotypes in association with RA Mexican patients, a new prospect for
      antigen modulation.
AB  - Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a
      posttranslational modification called citrullination, originating the antigenic
      determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA).
      Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to
      form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless,
      results in association studies appear contradictory in different populations. The
      aim of the study was to analyze if the presence of three SNPs in PADI4 gene
      susceptibility haplotype (GTG) is associated with ACPA positivity in patients
      with RA. This was a cross-sectional study that included 86 RA patients and 98
      healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4
      gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA
      patients; interestingly, we found a new haplotype associated with RA with a
      higher frequency (GTC). There were no associations between polymorphisms and high
      scores in Spanish HAQ-DI and DAS-28, but we did find an association between
      RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an
      association between susceptibility haplotype presence and ACPA positivity.
      Further evidence about proteomic expression of this gene will determine its
      participation in antigenic generation and autoimmunity. 

PMID- 24454474
TI  - Induction of antinuclear antibodies by de novo autoimmune hepatitis regulates
      alloimmune responses in rat liver transplantation.
AB  - Concanavalin A (Con A) is a lectin originating from the jack-bean and well known
      for its ability to stimulate T cells and induce autoimmune hepatitis. We
      previously demonstrated the induction of immunosuppressive antinuclear
      autoantibody in the course of Con A-induced transient autoimmune hepatitis. This
      study aimed to clarify the effects of Con A-induced hepatitis on liver allograft
      rejection and acceptance. In this study, we observed the unique phenomenon that
      the induction of transient de novo autoimmune hepatitis by Con A injection
      paradoxically overcomes the rejection without any immunosuppressive drug and
      exhibits significantly prolonged survival after orthotopic liver transplantation
      (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and
      high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody
      response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10
      in OLT livers of Con A-injected recipients suggested the involvement of
      regulatory T cells in this unique phenomenon. Our present data suggest the
      significance of autoimmune responses against nuclear histone H1 and HMGB1 for
      competing allogeneic immune responses, resulting in the acceptance of liver
      allografts in experimental liver transplantation. 

PMID- 24454475
TI  - B epitope multiplicity and B/T epitope orientation influence immunogenicity of
      foot-and-mouth disease peptide vaccines.
AB  - Synthetic peptides incorporating protective B- and T-cell epitopes are candidates
      for new safer foot-and-mouth disease (FMD) vaccines. We have reported that
      dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154)
      linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and
      T-cell specific responses and confer protection to viral challenge, while
      juxtaposition of these epitopes in a linear peptide induces less efficient
      responses. To assess the relevance of B-cell epitope multivalency, dendrimers
      bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a
      widespread circulating serotype) were tested in CD1 mice and showed that
      multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in
      efficient induction of neutralizing antibodies and optimal release of IFN gamma .
      Interestingly, the bivalent B2T construction elicited similar or even better B-
      and T-cell specific responses than tetravalent B4T. In addition, the presence of
      the T-cell epitope and its orientation were shown to be critical for the
      immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel.
      Taken together, our results provide useful insights for a more accurate design of
      FMD subunit vaccines. 

PMID- 24454476
TI  - Tregitope peptides: the active pharmaceutical ingredient of IVIG?
AB  - Five years ago, we reported the identification and characterization of several
      regulatory T-cell epitopes (now called Tregitopes) that were discovered in the
      heavy and light chains of IgG (De Groot et al. Blood, 2008). When added ex vivo
      to human PBMCs, these Tregitopes activated regulatory T cells (Tregs), increased
      expression of the transcription factor FoxP3, and induced IL-10 expression in
      CD4(+) T cells. We have now shown that coadministration of the Tregitopes in
      vivo, in a number of different murine models of autoimmune disease, can suppress
      immune responses to antigen in an antigen-specific manner, and that this response
      is mediated by Tregs. In addition we have shown that, although these are
      generally promiscuous epitopes, the activity of individual Tregitope peptides is
      restricted by HLA. In this brief report, we provide an overview of the effects of
      Tregitopes in vivo, discuss potential applications, and suggest that Tregitopes
      may represent one of the "active pharmaceutical ingredients" of IVIg. Tregitope
      applications may include any of the autoimmune diseases that are currently
      treated almost exclusively with intravenous immunoglobulin G (IVIG), such as
      Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Multifocal Motor
      Neuropathy (MMN), as well as gene therapy and allergy where Tregitopes may
      provide a means of inducing antigen-specific tolerance. 

PMID- 24454478
TI  - Clinical and experimental immunomodulation.

PMID- 24454477
TI  - Th17-associated cytokines as a therapeutic target for steroid-insensitive asthma.
AB  - Steroid-insensitive asthma is an infrequent but problematic airway disease that
      presents with persistent symptoms, airflow limitation, or recurrent exacerbations
      even when treated with steroid-based therapies. Because of unsatisfactory results
      obtained from currently available therapies for steroid-insensitive asthma, a
      better understanding of its pathogenesis and the development of new targeted
      molecular therapies are warranted. Recent studies indicated that levels of
      interleukin (IL)-17 are increased and both eosinophils and neutrophils infiltrate
      the airways of severe asthmatics. IL-17 is a proinflammatory cytokine mainly
      secreted from helper T (Th) 17 cells and is important for the induction of
      neutrophil recruitment and migration at sites of inflammation. This review
      focuses on the pathogenetic role of Th17 cells and their associated cytokines in
      steroid-insensitive asthma and discusses the prospects of novel therapeutic
      options targeting the Th17 signaling pathway. 

PMID- 24454479
TI  - Immune response following liver transplantation compared to kidney
      transplantation: usefulness of monitoring peripheral blood CD4+ adenosine
      triphosphate activity and cytochrome P450 3A5 genotype assay.
AB  - Seventy living donor liver transplantation (LDLT) and 39 kidney transplantation
      (KT) patients were randomly screened by using the peripheral blood CD4+ adenosine
      triphosphate activity (ATP) assay (IMK assay). The patients were divided into 2
      groups in each organ transplantation with low IMK ATP level (<225 ng/mL) or high
      (>225) (LT-L: n = 23, KT-L: n = 19, LT-H: n = 47, and KT-H: n = 20, resp.). The
      incidence of bacterial and/or viral infection was significantly higher in LT-L
      group than in LT-H group (74.0 versus 8.5%: P < 0.001). Occurrence of total viral
      infection in KT-L was also significantly higher than that in KT-H (36.8 versus
      10%: P = 0.046). The sensitivity and specificity of the IMK assay for identifying
      risk of infection was 0.810 and 0.878 in LDLT patients and 0.727 and 0.607 in KT
      patients. The percentage of LDLT patients with cytochrome P450 3A5 (CYP3A5) *1/*1
      or *1/*3 genotype (expressors) was significantly higher in LT-L group than in LT
      H group (53.8 versus 20.7%: P = 0.032). In both LDLT and KT patients, the IMK
      assay can be useful for monitoring immunological aspects of bacterial and/or
      viral infection. CYP3A5 expressors in LT-L group are related to postoperative
      infections.

PMID- 24454480
TI  - The multifaceted role of Th17 lymphocytes and their associated cytokines in
      cancer.
AB  - While the role of T helper 17 lymphocytes (Th17) in the pathogenesis of
      autoimmune diseases and in infectious immunity has been relatively well defined,
      the impact of these cells and their associated cytokines on cancer development is
      still under debate. Although multiple reports have indicated that Th17 can
      promote anticancer immunity, others have argued that these cells may exhibit
      tumor-promoting properties. This dichotomy in the function of Th17 lymphocytes in
      cancer may be related to the versatile nature of these cells, being capable of
      differentiating into either proinflammatory Th1 or suppressive FoxP3-expressing
      Treg cells or hybrid T cell subsets depending on the underlying environmental
      conditions. In the current review, we examine the role of Th17 lymphocytes and
      Th17-associated cytokines in cancer and discuss how factors that control their
      final lineage commitment decision may influence the balance between their tumor
      promoting versus tumor-suppressing properties. 

PMID- 24454482
TI  - Cornel Iridoid Glycoside Attenuates Tau Hyperphosphorylation by Inhibition of
      PP2A Demethylation.
AB  - Aim. The aim of the present study was to investigate the effect of cornel iridoid
      glycoside (CIG) on tau hyperphosphorylation induced by wortmannin (WT) and GF
      109203X (GFX) and the underlying mechanisms. Methods. Human neuroblastoma SK-N-SH
      cells were preincubated with CIG (50, 100, and 200 ug/ml, resp.) for 24 h and
      then exposed to 10 uM WT and 10 uM GFX for 3 h after washing out CIG.
      Immunohistochemistry was used to observe the microtubular cytoskeleton of the
      cultured cells. Western blotting was used to measure the phosphorylation level of
      tau protein, glycogen synthase kinase 3 beta (GSK-3 beta ), and protein
      phosphatase 2A (PP2A). The activity of PP2A was detected by a biochemical assay.
      Results. Preincubation of CIG significantly attenuated the WT/GFX-induced tau
      hyperphosphorylation at the sites of Thr205, Thr212, Ser214, Thr217, Ser396, and
      PHF-1 and improved the damage of morphology and microtubular cytoskeleton of the
      cells. CIG did not prevent the decrease in p-AKT-ser473 and p-GSK-3 beta -ser9
      induced by WT/GFX. However, CIG significantly elevated the activity of PP2A by
      reducing the demethylation of PP2A catalytic subunit (PP2Ac) at Leu309 and the
      ratio of PME-1/LCMT in the WT/GFX-treated cells. The results suggest that CIG may
      be beneficial to the treatment of AD. 

PMID- 24454483
TI  - Fermented wheat germ extract induced cell death and enhanced cytotoxicity of
      Cisplatin and 5-Fluorouracil on human hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related
      death worldwide. Due to the difficulties of early diagnosis, curative treatments
      are not available for most patients. Palliative treatments such as chemotherapy
      are often associated with low response rate, strong adverse effects and limited
      clinical benefits for patients. The alternative approaches such as fermented
      wheat germ extract (FWGE) with anti-tumor efficacy may provide improvements in
      the clinical outcome of current therapy for HCC. This study aimed to clarify
      antitumor efficacy of FWGE and the combination drug effect of FWGE with
      chemotherapeutic agents, cisplatin and 5-fluorouracil (5-Fu) in human HCC cells,
      HepG2, Hep3B, and HepJ5. The present study indicated that FWGE exhibited
      potential to suppress HepG2, Hep3B, and HepJ5 cells, with the half maximal
      inhibitory concentrations (IC50) of FWGE were 0.494, 0.371 and 1.524 mg/mL,
      respectively. FWGE also induced Poly (Adenosine diphosphate ribose) polymerase
      (PARP) associated cell death in Hep3B cells. Moreover, the FWGE treatment further
      enhanced the cytotoxicity of cisplatin in all tested HCC cells, and cytotoxicity
      of 5-Fu in a synergistic manner in HepJ5 cells. Collectively, the results
      identified the anti-tumor efficacy of FWGE in HCC cells and suggested that FWGE
      can be used as a supplement to effectively improve the tumor suppression
      efficiency of cisplatin and 5-Fu in HCC cells. 

PMID- 24454484
TI  - Integrative oncology.

PMID- 24454481
TI  - Th17 cells in immunity and autoimmunity.
AB  - Th17 and IL-17 play important roles in the clearance of extracellular bacterial
      and fungal infections. However, strong evidence also implicates the Th17 lineage
      in several autoimmune disorders including multiple sclerosis, psoriasis,
      rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus,
      and asthma. The Th17 subset has also been connected with type I diabetes,
      although whether it plays a role in the pathogenicity of or protection from the
      disease remains a controversial issue. In this review we have provided a
      comprehensive overview of Th17 pathogenicity and function, including novel
      evidence for a protective role of Th17 cells in conjunction with the microbiota
      gut flora in T1D onset and progression. 

PMID- 24454485
TI  - Validating efficacy of shea nut oil extract in knee osteoarthritis patients.
AB  - Objectives. To examine and investigate the efficacy of shea nut oil extract
      (SheaFlex75) in relation to knee osteoarthritis (OA). Methods. Thirty-three
      patients (age 63.6 +/- 5.8 years) with knee OA were recruited. Real-time
      ultrasound imaging and surface electromyography were used to objectively assess
      the morphological changes and the activity of vastus medialis oblique (VMO)
      muscles during a 16-week intervention of SheaFlex75. The intraclass correlation
      coefficient (ICC) was calculated to examine the reliability of the interscans. A
      paired-sample t-test was used to compare the findings in different stages. The
      Spearman's rank correlation coefficient was used to examine the relationship
      between the relevant variables of OA and percentage of thickness change of VMO at
      different contraction levels. Results. The baseline findings showed strong
      correlation, suggesting that the reliability of interscans at pretest was high.
      The ability to contract the muscles of the knee to a 30% contraction level showed
      significant change between the baseline and after 16-week testing, both in terms
      of morphological changes and muscle activity. Pain scale reported a significant
      decrease at the 16th week. Conclusion. The results suggest that SheaFlex75 can
      relieve the symptoms of knee OA and can result in improvement of muscle control
      of the knee. 

PMID- 24454486
TI  - Comparison of Gut Microbiota between Sasang Constitutions.
AB  - The Sasang constitutional medicine has long been applied to diagnose and treat
      patients with various diseases. Studies have been conducted for establishment of
      scientific evidence supporting Sasang Constitutional (SC) diagnosis. Recent human
      microbiome studies have demonstrated individual variations of gut microbiota
      which can be dependent on lifestyle and health conditions. We hypothesized that
      gut microbial similarities and discrepancies may exist across SC types. We
      compared the difference of gut microbiota among three constitutions (So-Yang, So
      Eum, and Tae-Eum), along with the investigation of anthropometric and biochemical
      parameters. Firmicutes and Bacteroidetes were predominant phyla in all SC types.
      The median plot analysis suggested that Firmicutes and Bacteroidetes appeared
      more abundant in SE and TE, respectively, in the male subjects of 20-29 years
      old. At the genus level, Bifidobacterium and Bacteroides manifested the
      difference between SE and TE types. For anthropometry, body weight, body mass
      index, and waist circumference of the TE type were significantly higher than
      those of the other types. Overall, findings indicated a possible link between SC
      types and gut microbiota within a narrow age range. Further investigations are
      deemed necessary to elucidate the influences of age, gender, and other factors in
      the context of SC types and gut microbiota. 

PMID- 24454487
TI  - Nigella sativa Oil Enhances the Spatial Working Memory Performance of Rats on a
      Radial Arm Maze.
AB  - Nigella sativa, an established historical and religion-based remedy for a wide
      range of health problems, is a herbal medicine known to have antioxidant and
      neuroprotective effects. This present study investigated the effect of Nigella
      sativa oil (NSO) administration on the spatial memory performance (SMP) of male
      adult rats using eight-arm radial arm maze (RAM). Twelve Sprague Dawley rats (7-9
      weeks old) were force-fed daily with 6.0  MU L/100 g body weight of Nigella
      sativa oil (NSO group; n = 6) or 0.1 mL/100 g body weight of corn oil (control)
      (CO group; n = 6) for a period of 20 consecutive weeks. For each weekly
      evaluation of SMP, one day food-deprived rats were tested by allowing each of
      them 3 minutes to explore the RAM for food as their rewards. Similar to the
      control group, the SMP of the treated group was not hindered, as indicated by the
      establishment of the reference and working memory components of the spatial
      memory. The results demonstrated that lesser mean numbers of error were observed
      for the NSO-treated group in both parameters as compared to the CO-treated group.
      NSO could therefore enhance the learning and memory abilities of the rats; there
      was a significant decrease in the overall mean number of working memory error
      (WME) in the NSO-treated group. 

PMID- 24454488
TI  - A C 21 -Steroidal Glycoside Isolated from the Roots of Cynanchum auriculatum
      Induces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells.
AB  - Caudatin 3-O-beta-D-cymaropyranosyl-(1 -> 4)-beta-D-oleandropyranosyl-(1 -> 4)
      beta-D-cymaropyranosyl-(1 -> 4)-beta-D-cymaropyranoside (CGII) is one of the C21
      steroidal glycosides isolated from the roots of Cynanchum auriculatum ROYLE ex
      WIGHT. This study aimed to determine the cell growth, cell proliferation, and
      apoptotic cell death of human gastric cancer cells after CGII treatment. MTT
      assay was used to determine cell growth; fluorescence-activated cell sorting
      analysis was used to evaluate cell cycle distribution and apoptotic cell death.
      Immunoblotting was applied for measuring the expression of proteins involved in
      the cell cycle progression. The activities of caspase-3, -8, and -9 were detected
      by colorimetric caspase activity assays. CGII inhibited cell growth of human
      gastric cancer SGC-7901 cells in a concentration- and time-dependent manner.
      Treatment of SGC-7901 cells with CGII resulted in G1 phase cell cycle arrest,
      accompanied with decreased expression of cyclin D1 and cyclin-dependent kinases 4
      and 6. CGII induced cell apoptosis and activated caspase-3, caspase-8, and
      caspase-9. In contrast, pan-caspase inhibitor z-VAD-fmk partially abolished the
      CGII-induced growth inhibition of SGC-7901 cells. In conclusion, CGII inhibits
      cell growth of human gastric cancer cells by inducing G1 phase cell cycle arrest
      and caspase-dependent apoptosis cascades. 

PMID- 24454489
TI  - Mixed Methods in CAM Research: A Systematic Review of Studies Published in 2012.
AB  - Background. Mixed methods research uses qualitative and quantitative methods
      together in a single study or a series of related studies. Objectives. To review
      the prevalence and quality of mixed methods studies in complementary medicine.
      Methods. All studies published in the top 10 integrative and complementary
      medicine journals in 2012 were screened. The quality of mixed methods studies was
      appraised using a published tool designed for mixed methods studies. Results. 4%
      of papers (95 out of 2349) reported mixed methods studies, 80 of which met
      criteria for applying the quality appraisal tool. The most popular formal mixed
      methods design was triangulation (used by 74% of studies), followed by embedded
      (14%), sequential explanatory (8%), and finally sequential exploratory (5%).
      Quantitative components were generally of higher quality than qualitative
      components; when quantitative components involved RCTs they were of particularly
      high quality. Common methodological limitations were identified. Most strikingly,
      none of the 80 mixed methods studies addressed the philosophical tensions
      inherent in mixing qualitative and quantitative methods. Conclusions and
      Implications. The quality of mixed methods research in CAM can be enhanced by
      addressing philosophical tensions and improving reporting of (a) analytic methods
      and reflexivity (in qualitative components) and (b) sampling and recruitment
      related procedures (in all components). 

PMID- 24454491
TI  - Evidence of Antidepressive Effects of a Wakan-yaku, Hochuekkito, in Depression
      Model Mice with Learned-Helplessness Behavior.
AB  - Wakan-yaku is a type of Japanese and Sino traditional, systematized medical care
      that has been practiced for hundreds of years. This medicinal system includes
      many antidepressive prescriptions. One of the candidates is Hochuekkito, although
      experimental evidence has not yet been established clearly. To obtain evidence, a
      depression model of learned-helplessness (LH) mice was used. Based on the score
      of escape failure, an index of the depression degree, mice with a depressive
      condition were selected to assess Hochuekkito's effects. This selection was
      significant and effective in the following two points: evaluation of the drug
      effect under disease conditions and minimization of the number of animals.
      Treatment with Hochuekkito (1 and 5 g/kg p.o.; estimated galenical amount) for 14
      days significantly decreased the depression index, the number of escape failures,
      and desipramine (10 mg/kg p.o.) suggesting that Hochuekkito has an antidepressive
      effect. 

PMID- 24454492
TI  - Evodiamine Induces Transient Receptor Potential Vanilloid-1-Mediated Protective
      Autophagy in U87-MG Astrocytes.
AB  - Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which
      results in cognitive and motor dysfunction, neurodegenerative diseases, and
      death. Evodiamine (Evo) is extracted from Evodia rutaecarpa Bentham, a plant
      widely used in Chinese herbal medicine, which possesses variable biological
      abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer's
      disease, antimetastatic, antianoxic, and antinociceptive functions. But the
      effect of Evo on ischemic stroke is unclear. Increasing data suggest that
      activation of autophagy, an adaptive response to environmental stresses, could
      protect neurons from ischemia-induced cell death. In this study, we found that
      Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium
      and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased
      the percentage of autophagy accompanied by an increase in apoptosis, suggesting
      that Evo may induce calcium-mediated protective autophagy resulting from an
      influx of extracellular calcium. The same phenomena were also confirmed by a
      small interfering RNA technique to knock down the expression of TRPV1. Finally,
      Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1
      antagonist, indicating that Evo-induced autophagy may occur through a calcium/c
      Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of
      extracellular calcium, which led to JNK-mediated protective autophagy, and this
      provides a new option for ischemic stroke treatment. 

PMID- 24454493
TI  - Acupoint stimulation for fibromyalgia: a systematic review of randomized
      controlled trials.
AB  - Background. Acupoint stimulation is popular for treatment of fibromyalgia though
      there is lack of comprehensive evaluation of current clinical evidence for its
      effect and safety. Objective. To systematically review the beneficial effects and
      safety of acupoint stimulation for fibromyalgia. Methods. We searched six
      electronic databases for randomized trials on acupoint stimulation for treatment
      of fibromyalgia. Two authors extracted data and assessed the trial quality
      independently. RevMan 5.2 software was used for data analyses with effect
      estimate presented as (standard) mean difference and a 95% confidence interval.
      We defined minimum, medium, and large SMD effect sizes as 0.3, 0.5, and 0.75.
      Results. 16 RCTs with 1081 participants were involved in this review. Only two
      trials were evaluated as low risk of bias. Meta-analysis showed that acupuncture
      alone or combined with cupping therapy was superior to conventional medications
      on reducing pain scores and/or the number of tender points. However, acupuncture
      showed no better than sham acupuncture on pain reduction. There was no serious
      adverse event reported to be related to acupoint stimulation. Conclusions.
      Acupoint stimulation appears to be effective in treating fibromyalgia compared
      with medications. However, further large, rigorously designed trials are
      warranted due to insufficient methodological rigor in the included trials. 

PMID- 24454495
TI  - In Vitro Screening for Antihepatic Steatosis Active Components within Coptidis
      Rhizoma Alkaloids Extract Using Liver Cell Extraction with HPLC Analysis and a
      Free Fatty Acid-Induced Hepatic Steatosis HepG2 Cell Assay.
AB  - A high-throughput method was developed and applied to screen for the active
      antihepatic steatosis components within Coptidis Rhizoma Alkaloids Extract (CAE).
      This method was a combination of two previously described assays: HepG2 cell
      extraction with HPLC analysis and a free fatty acid-induced (FFA) hepatic
      steatosis HepG2 cell assay. Two alkaloids within CAE, berberine and coptisine,
      were identified by HepG2 cell extraction with HPLC analysis as high affinity
      components for HepG2. These alkaloids were also determined to be active and
      potent compounds capable of lowering triglyceride (TG) accumulation in the FFA
      induced hepatic steatosis HepG2 cell assay. This remarkable inhibition of TG
      accumulation (P < 0.01) by berberine and coptisine occurred at concentrations of
      0.2  MU g/mL and 5.0 MU g/mL, respectively. At these concentrations, the effect
      seen was similar to that of a CAE at 100.0  MU g/mL. Another five alkaloids
      within CAE, palmatine, epiberberine, jateorhizine, columbamine, and magnoline,
      were found to have a lower affinity for cellular components from HepG2 cells and
      a lower inhibition of TG accumulation. The finding of two potent and active
      compounds within CAE indicates that the screening method we developed is a
      feasible, rapid, and useful tool for studying traditional Chinese medicines
      (TCMs) in treating hepatic steatosis. 

PMID- 24454494
TI  - Does the couse of astragalus-containing chinese herbal prescriptions and
      radiotherapy benefit to non-small-cell lung cancer treatment: a meta-analysis of
      randomized trials.
AB  - Background. Radiotherapy has been widely used for non-small-cell lung cancer
      (NSCLC), while its low efficacy and high toxicity raise big concerns. Astragalus
      (as a monarch drug)-containing Chinese herbal prescriptions and radiotherapy were
      frequently coused for NSCLC in China; however, the effects were not
      systematically analyzed. Objective. To evaluate the benefits of Astragalus
      containing Chinese herbal prescriptions combined with radiotherapy for NSCLC.
      Methods. The randomized controlled trials involving NSCLC treatment with
      Astragalus-containing Chinese herbal prescriptions combined with radiotherapy
      were searched. The Review Manager 5.1 software was employed for data analysis.
      Funnel plot and Egger's test were applied to evaluate publication bias. Results.
      29 eligible studies met our criteria. Of the studies, 8, 6, and 4 reported
      reduced risk of death at one year, two years, and three years, respectively. 26
      studies revealed amended tumor response. Six studies showed improved Karnofsky
      performance status. Among the studies, 14 and 18 displayed a lowered white blood
      cells (WBC) toxicity and an ameliorated radiation pneumonia, respectively.
      Conclusion. Couse of Astragalus-containing Chinese herbal prescriptions and
      radiotherapy may benefit the patients with NSCLC via increasing the therapeutic
      effectiveness and reducing the toxicity of radiotherapy. To confirm the exact
      merits, further rigorously designed trials are warranted. 

PMID- 24454496
TI  - In Vitro Global Gene Expression Analyses Support the Ethnopharmacological Use of
      Achyranthes aspera.
AB  - Achyranthes aspera (family Amaranthaceae) is known for its anticancer properties.
      We have systematically validated the in vitro and in vivo anticancer properties
      of this plant. However, we do not know its mode of action. Global gene expression
      analyses may help decipher its mode of action. In the absence of identified
      active molecules, we believe this is the best approach to discover the mode of
      action of natural products with known medicinal properties. We exposed human
      pancreatic cancer cell line MiaPaCa-2 (CRL-1420) to 34  MU g/mL of LE for 24, 48,
      and 72 hours. Gene expression analyses were performed using whole human genome
      microarrays (Agilent Technologies, USA). In our analyses, 82 (54/28) genes passed
      the quality control parameter, set at FDR <= 0.01 and FC of >=+/-2. LE
      predominantly affected pathways of immune response, metabolism, development, gene
      expression regulation, cell adhesion, cystic fibrosis transmembrane conductance
      regulation (CFTR), and chemotaxis (MetaCore tool (Thomson Reuters, NY)). Disease
      biomarker enrichment analysis identified LE regulated genes involved in
      Vasculitis-inflammation of blood vessels. Arthritis and pancreatitis are two of
      many etiologies for vasculitis. The outcome of disease network analysis supports
      the medicinal use of A. aspera, viz, to stop bleeding, as a cure for pancreatic
      cancer, as an antiarthritic medication, and so forth. 

PMID- 24454497
TI  - Zheng classification with missing feature values using local-validity approach.
AB  - Zheng classification is a very important step in the diagnosis of traditional
      Chinese medicine (TCM). In clinical practice of TCM, feature values are often
      missing and incomplete cases. The performance of Zheng classification is strictly
      related to rates of missing feature values. Based on the pattern of the missing
      feature values, a new approach named local-validity is proposed to classify zheng
      classification with missing feature values. Firstly, the maximum submatrix for
      the given dataset is constructed and local-validity method finds subsets of cases
      for which all of the feature values are available. To reduce the computational
      scale and improve the classification accuracy, the method clusters subsets with
      similar patterns to form local-validity subsets. Finally, the proposed method
      trains a classifier for each local-validity subset and combines the outputs of
      individual classifiers to diagnose zheng classification. The proposed method is
      applied to the real liver cirrhosis dataset and three public datasets.
      Experimental results show that classification performance of local-validity
      method is superior to the widely used methods under missing feature values. 

PMID- 24454498
TI  - Complementary/Alternative medicine in cardiovascular diseases 2013.

PMID- 24454500
TI  - Randomized clinical trial: the clinical effects of herb-partitioned moxibustion
      in patients with diarrhoea-predominant irritable bowel syndrome.
AB  - Objective. To explore the efficacy of Herb-partitioned moxibustion in treating
      IBS-D patients. Method. 210 IBS-D patients were randomly assigned on a 3 : 3 : 2
      basis to group HM, group FM, or group PB for 4-week treatment. The change of GSRS
      total score at weeks 4 and 8, the changes of GSRS specific scores, and adverse
      events were evaluated. Results. Patients in group HM and group FM had lower GSRS
      total score at week 4 (1.98 +/- 0.303, 2.93 +/- 0.302 versus 3.73 +/- 0.449) and
      at week 8 (2.75 +/- 0.306, 3.56 +/- 0.329 versus 4.39 +/- 2.48) as compared with
      patients' score in group PB. However, there was no significant difference of GSRS
      total score between group HM and group FM. The effect of HM was significantly
      greater than that of orally taking PB in ameliorating the symptoms of rugitus
      (0.38 versus 0.59, P < 0.05), abdominal pain (0.28 versus 0.57, P < 0.01),
      abdominal distension (0.4 versus 0.7, P < 0.01), and increased passage of stools
      (0.06 versus 0.25, P < 0.01) at the end of treatment period. In the follow-up
      period, patients' therapeutic effect in group HM remained greater than that in
      group FM (in abdominal pain, abdominal distension, and increased passage of
      stools) and that in group PB (in loose stools). Conclusions. HM appears to be a
      promising, efficacious, and well-tolerated treatment for patients with IBS-D. 

PMID- 24454499
TI  - Melinjo (Gnetum gnemon L.) Seed Extract Decreases Serum Uric Acid Levels in
      Nonobese Japanese Males: A Randomized Controlled Study.
AB  - Melinjo (Gnetum gnemon L.) seed extract (MSE) containing trans-resveratrol
      (3,5,4'-trihydroxy-trans-stilbene) and other derivatives exerts various
      beneficial effects. However, its mechanism of action in humans remains unknown.
      In this study, we aimed to investigate beneficial effects of MSE in healthy adult
      males. In this double-blind, randomized controlled study, 30 males aged 35-70
      years with <=10% flow-mediated dilatation received placebo or 750 mg MSE powder
      for 8 weeks, and twenty-nine males (45.1 +/- 8.8 years old) completed the trial.
      There was a significant difference in the melinjo and placebo groups. Compared
      with the placebo control, MSE significantly reduced serum uric acid at 4 weeks
      and 8 weeks (n = 14 and 15, resp.). HDL cholesterol was significantly increased
      in the melinjo group. To clarify the mechanism of MSE for reducing uric acid, we
      investigated xanthine oxidase inhibitory activity, angiotensin II type 1 (AT1)
      receptor binding inhibition rate, and agonistic activities for PPAR alpha and
      PPAR gamma . MSE, trans-resveratrol, and a resveratrol dimer, gnetin C (GC),
      significantly inhibit AT1 receptor binding and exhibit mild agonistic activities
      for PPAR alpha and PPAR gamma . In conclusion, MSE may decrease serum uric acid
      regardless of insulin resistance and may improve lipid metabolism by increasing
      HDL cholesterol. 

PMID- 24454501
TI  - Addressing the "It Is Just Placebo" Pitfall in CAM: Methodology of a Project to
      Develop Patient-Reported Measures of Nonspecific Factors in Healing.
AB  - CAM therapies are often dismissed as "no better than placebo;" however, this
      belief may be overcome through careful analysis of nonspecific factors in
      healing. To improve trial methodology, we propose that CAM (and conventional)
      RCTs should evaluate and adjust for the effects of intrapersonal, interpersonal,
      and environmental factors on outcomes. However, measurement of these is
      challenging, and there are no brief, precise instruments that are suitable for
      widespread use in trials and clinical settings. This paper describes the
      methodology of a project to develop a set of patient-reported instruments that
      will quantify the nonspecific or "placebo" effects that are in fact specific and
      active ingredients in healing. The project uses the rigorous instrument
      development methodology of the NIH-PROMIS initiative. The methods include (1)
      integration of patients' and clinicians' opinions with existing literature; (2)
      development of relevant items; (3) calibration of items on large samples; (4)
      classical test theory and modern psychometric methods to select the most useful
      items; (5) development of computerized adaptive tests (CATs) that maximize
      information while minimizing patient burden; and (6) initial validation studies.
      The instruments will have the potential to revolutionize clinical trials in both
      CAM and conventional medicine through quantifying contextual factors that
      contribute to healing. 

PMID- 24454502
TI  - A single-center, randomized double-blind placebo-controlled study evaluating the
      effects of poly-gamma-glutamate on human NK cell activity after an 8-week oral
      administration in healthy volunteers.
AB  - A randomized double-blind placebo-controlled immunity study involving 99 healthy
      volunteers was performed to investigate the effect of poly- gamma -glutamate (
      gamma -PGA) on human natural killer (NK) cell activity in peripheral blood. The
      volunteers were randomly assigned to one of three groups and orally treated with
      solutions (25 mL) containing 0 mg (placebo), 250 mg (low dosage), or 500 mg (high
      dosage) of gamma -PGA. Each volunteer took one dose every 12 hours for 8 weeks.
      Blood samples were drawn before the initial treatment and at the 4th and the 8th
      weeks of treatment. NK cell activity was assessed by measuring its degranulation,
      cytokine production, and cytotoxicity against the K562 cell line. Our results
      revealed that the cytotoxic activities of NK cells from the high-dosage gamma 
      PGA group were significantly higher (P < 0.05 for all comparisons) compared to
      the low dosage and placebo groups at weeks 4 and 8 after the initial treatment.
      This increase in the NK cell activity among peripheral blood mononuclear cells
      (PBMCs) of healthy individuals was also confirmed in vitro (as assessed by the
      degranulation and cytokine production). These results suggest that the oral
      administration of gamma -PGA induces a cell-mediated immunity by increasing the
      NK cell activity in humans. 

PMID- 24454503
TI  - Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic
      Activities.
AB  - Fruit from the palm Mauritia flexuosa is one of the most important species in
      Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed
      to investigate the antiplatelet and antithrombotic activities of oil extracted
      from Mauritia flexuosa. The fatty acid contents were determined by gas
      chromatography-mass spectrometry. Oil extract of peel of Mauritia flexuosa was
      extracted by soxhlet extraction. The oil extract inhibited platelet secretion and
      aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way
      (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and
      diminished platelet rolling and firm adhesion under flow conditions. Furthermore,
      the oil extract induced a marked increase in the rolling speed of leukocytes
      retained on the platelet surface, reflecting a reduction of rolling and less
      adhesion. At the concentrations used, the oil extract significantly decreased
      platelet release of sP-selectin, an atherosclerotic-related inflammatory
      mediator. Oil extract inhibited thrombus growth at the same concentration as that
      of aspirin, a classical reference drug. Finally, the data presented herein also
      demonstrate for the first time to our knowledge the protective effect of oil
      extracted from Mauritia flexuosa on platelet activation and thrombosis formation.

PMID- 24454504
TI  - Complementary and alternative therapies for liver diseases.

PMID- 24454490
TI  - The globalization of traditional medicine in northern peru: from shamanism to
      molecules.
AB  - Northern Peru represents the center of the Andean "health axis," with roots going
      back to traditional practices of Cupisnique culture (1000 BC). For more than a
      decade of research, semistructured interviews were conducted with healers,
      collectors, and sellers of medicinal plants. In addition, bioassays were carried
      out to evaluate the efficacy and toxicity of plants found. Most of the 510
      species encountered were native to Peru (83%). Fifty percent of the plants used
      in colonial times have disappeared from the pharmacopoeia. Market vendors
      specialized either on common and exotic plants, plants for common ailments, and
      plants only used by healers or on plants with magical purposes. Over 974
      preparations with up to 29 different ingredients were used to treat 164 health
      conditions. Almost 65% of the medicinal plants were applied in these mixtures.
      Antibacterial activity was confirmed in most plants used for infections. Twenty
      four percent of the aqueous extracts and 76% of the ethanolic extracts showed
      toxicity. Traditional preparation methods take this into account when choosing
      the appropriate solvent for the preparation of a remedy. The increasing demand
      for medicinal species did not increase the cultivation of medicinal plants. Most
      species are wild collected, causing doubts about the sustainability of trade. 

PMID- 24454505
TI  - Cerebrospinal fluid pharmacology: an improved pharmacology approach for chinese
      herbal medicine research.
AB  - Despite many successful applications of Chinese herbal medicine (CHM) in the
      treatment and prevention of neurological diseases (ND), the fully scientific
      understanding of CHM's action mechanisms had been hampered for lack of
      appropriate methods to explore the combinatorial rules, the synergistic
      mechanisms, and the molecular basis of CHM. As an improved pharmacology approach,
      cerebrospinal fluid pharmacology (CSFP), based on the fact that cerebrospinal
      fluid plays an important role in the health maintenance of specific survival
      environment for neurons and glial cells, has been constructed and applied to CHM
      research for treating ND. In the present review, the concept and advantages of
      CSFP are briefly introduced. The approaches and key technologies of CSFP in CHM
      research are also collated and analyzed. Furthermore, the developing tendency of
      CSFP is summarized, and its framework in CHM research is also proposed. In
      summary, CSFP provides a new strategy not only to eliminate some barriers of CHM
      research for treating ND, but also to broaden the pharmacology research for
      bridging the gap between CHM and modern medicine. Moreover, the advancements in
      CSFP will bring about a conceptual move in active ingredients discovery of CHM
      and make a significant contribution to CHM modernization and globalization. 

PMID- 24454507
TI  - Natural bioactives and phytochemicals serve in cancer treatment and prevention.

PMID- 24454506
TI  - Protective Effects of Lycium barbarum Polysaccharides on Testis Spermatogenic
      Injury Induced by Bisphenol A in Mice.
AB  - To observe the effects of Lycium barbarum polysaccharides (LBP) on testis
      spermatogenic injuries induced by Bisphenol A (BPA) in mice. BPA was
      subcutaneously injected into mice at a dose of 20 mg/kg body weight (BW) for 7
      consecutive days. LBP was administered simultaneously with BPA by gavage daily at
      the dose of 50, 100, and 200 mg/kg BW for 7 days. After treatment, the weight and
      the histopathology changes of testis and epididymis were examined; the contents
      of T, LH, GnRH, antioxidant enzyme, and malondialdehyde (MDA) in serum were
      detected; proapoptotic protein Bax and antiapoptotic protein Bcl-2 were also
      detected by immunohistochemical method. Results showed that the weights of testis
      and epididymis were all increased after supplement with different dosages of LBP
      compared with BPA group, and the activities of SOD and GSH-Px were significantly
      increased in LBP groups, while MDA contents were gradually decreased. Moreover,
      the levels of T, LH, and GnRH were significantly elevated in serum treated with
      100 mg/kg LBP. LBP also shows significant positive effects on the expression of
      Bcl-2/Bax in BPA treated mice. It is concluded that LBP may be one of the
      potential ingredients protecting the adult male animals from BPA induced
      reproductive damage. 

PMID- 24454508
TI  - Autonomic Nervous System Mediates the Hypotensive Effects of Aqueous and Residual
      Methanolic Extracts of Syzygium polyanthum (Wight) Walp. var. polyanthum Leaves
      in Anaesthetized Rats.
AB  - Syzygium polyanthum (Wight) Walp. var. polyanthum leaves are consumed as a
      traditional Malay treatment of hypertension. This study investigates hypotensive
      potential of aqueous (AESP) and residual methanolic (met-AESP) extracts of S.
      polyanthum leaves and possible involvement of autonomic receptors. AESP and met
      AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar
      Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart
      were monitored for 20 min. AESP and met-AESP induced significant dose-dependent
      hypotension, but only 100 mg/kg AESP caused mild bradycardia (n = 5). AESP
      induced hypotension was more potent than that of met-AESP in WKY. AESP has a
      faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP
      induced hypotension was more sustained than that of AESP in SHR. Blockages of
      autonomic ganglion and alpha -adrenergic receptors using hexamethonium and
      phentolamine (n = 5 for each group) partially attenuated AESP-induced
      hypotension, suggesting involvement of alpha -adrenergic receptors. Blockages of
      autonomic ganglion, beta -adrenergic, cholinergic receptors, and nitric oxide
      production using hexamethonium, propranolol, atropine, and N- omega -nitro-l
      arginine methyl ester (L-NAME) (n = 5 for each group) partially attenuated met
      AESP-induced hypotension, suggesting involvement of beta -adrenergic and
      cholinergic receptors via nitric oxide production. 

PMID- 24454509
TI  - Relationship between EGF, TGFA, and EGFR Gene Polymorphisms and Traditional
      Chinese Medicine ZHENG in Gastric Cancer.
AB  - In traditional Chinese medicine (TCM), correct syndrome differentiation is the
      most important principle guiding the prescription of Chinese herbal formulae for
      the treatment of gastric cancer (GC). We aimed to reveal the genetic mechanisms
      underlying GC syndrome differentiation (ZHENG) in a population of 387 GC
      patients. Twenty-nine single nucleotide polymorphisms (SNPs) in EGF, TGFA, and
      EGFR were investigated. Two SNPs, rs11466285 in TGFA and rs884225 in EGFR, were
      significantly associated with the distribution of ZHENG (P < 0.05). The
      rs11466285 TT genotype increased the risk of damp heat with toxin (DHT) and
      deficiency of both Qi and yin (DQY) compared with obstruction of blood stasis
      (OBS). The rs884225 AA genotype could increase the risk of DQY and deficiency of
      both Qi and blood (DQB) compared with yin deficiency due to stomach heat (YDSH).
      Parallel comparison among the SNPs and syndrome types revealed that DQB was
      distinct from YDSH, disharmony between the liver and stomach, stagnation of
      phlegm muddiness (SPM), OBS, and other syndromes at several SNP loci (P < 0.05).
      The rs11466285 TT and rs884225 AA genotypes exhibit increased risk of DQB
      compared with OBS and SPM (P < 0.05), respectively. In conclusion, the formation
      of GC ZHENG was related to EGF, TGFA, and EGFR gene polymorphisms. 

PMID- 24454510
TI  - Chinese herbal medicine for acute mountain sickness: a systematic review of
      randomized controlled trials.
AB  - Objectives. We aimed to assess the current clinical evidence of Chinese herbal
      medicine for AMS. Methods. Seven electronic databases were searched until January
      2013. We included randomized clinical trials testing Chinese herbal medicine
      against placebo, no drugs, Western drugs, or a combination of routine treatment
      drugs against routine treatment drugs. Study selection, data extraction, quality
      assessment, and data analyses were conducted according to Cochrane standards.
      Results. Nine randomized trials were included. The methodological quality of the
      included trials was evaluated as low. Two trials compared prescriptions of
      Chinese formula used alone with Western drugs. A meta-analysis showed a
      beneficial effect in decreasing the score of AMS (MD: -2.23 [-3.98, -0.49], P =
      0.01). Only one trial compared prescriptions of Chinese formula used alone with
      no drugs. A meta-analysis showed a significant beneficial effect in decreasing
      the score of AMS (MD: -6.00 [-6.45, -5.55], P < 0.00001). Four trials compared
      Chinese formula used alone with placebo. A meta-analysis also showed a
      significant beneficial effect in decreasing the score of AMS (MD: -1.10 [-1.64, 
      0.55], P < 0.0001). Two trials compared the combination of Chinese formula plus
      routine treatment drugs with routine treatment drugs. A meta-analysis showed a
      beneficial effect in decreasing the score of AMS (MD: -5.99 [-11.11, -0.86], P =
      0.02). Conclusions. No firm conclusion on the effectiveness and safety of Chinese
      herbal medicine for AMS can be made. More rigorous high-quality trials are
      required to generate a high level of evidence and to confirm the results. 

PMID- 24454511
TI  - Mediterranean Diet and Red Yeast Rice Supplementation for the Management of
      Hyperlipidemia in Statin-Intolerant Patients with or without Type 2 Diabetes.
AB  - Lipid profile could be modified by Mediterranean diet (MD) and by red yeast rice
      (RYR). We assessed the lipid-lowering effects of MD alone or in combination with
      RYR on dyslipidemic statin-intolerant subjects, with or without type 2 diabetes,
      for 24 weeks. We evaluated the low-density lipoprotein (LDL) cholesterol level,
      total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride,
      liver enzyme, and creatinine phosphokinase (CPK) levels. We studied 171 patients:
      46 type 2 diabetic patients treated with MD alone (Group 1), 44 type 2 diabetic
      patients treated with MD associated with RYR (Group 2), 38 dyslipidemic patients
      treated with MD alone (Group 3), and 43 dyslipidemic patients treated with MD
      plus RYR (Group 4). The mean percentage changes in LDL cholesterol from the
      baseline were -7.34 +/- 3.14% (P < 0.05) for Group 1; -21.02 +/- 1.63% (P <
      0.001) for Group 2; -12.47 +/- 1.75% (P < 0.001) for Group 3; and -22 +/- 2.19%
      (P < 0.001) for Group 4 with significant intergroup difference (Group 1 versus
      Group 2, P < 0.001; Group 3 versus Group 4, P > 0.05). No significant increase in
      AST, ALT, and CPK levels was observed in all groups. Our results indicate that MD
      alone is effective in reducing LDL cholesterol levels in statin-intolerant
      patients with a presumably low cardiovascular risk, but associating MD with the
      administration of RYR improves patients' LDL cholesterol levels more, and in
      patients with type 2 diabetes. 

PMID- 24454512
TI  - Static magnetic field effects on impaired peripheral vasomotion in conscious
      rats.
AB  - We investigated the SMF effects on hemodynamics in the caudal artery-ligated rat
      as an in vivo ischemia model using noninvasive near-infrared spectroscopy (NIRS)
      combined with power spectral analysis by fast Fourier transform. Male Wistar rats
      in the growth stage (10 weeks old) were randomly assigned into four groups: (i)
      intact and nonoperated cage control (n = 20); (ii) ligated alone (n = 20); (iii)
      ligated and implanted with a nonmagnetized rod (sham magnet; n = 22); and (vi)
      ligated and implanted with a magnetized rod (n = 22). After caudal artery
      ligation, a magnetized or unmagnetized rod (maximum magnetic flux density of 160
      mT) was implanted transcortically into the middle diaphysis of the fifth caudal
      vertebra. During the experimental period of 7 weeks, NIRS measurements were
      performed in 3- , 5- , and 7-week sessions and the vasomotion amplitude and
      frequency were analyzed by fast Fourier transform. Exposure for 3-7 weeks to the
      SMF significantly contracted the increased vasomotion amplitude in the ischemic
      area. These results suggest that SMF may have a regulatory effect on rhythmic
      vasomotion in the ischemic area by smoothing the vasomotion amplitude in the
      early stage of the wound healing process. 

PMID- 24454513
TI  - Perimenopause Amelioration of a TCM Recipe Composed of Radix Astragali, Radix
      Angelicae Sinensis, and Folium Epimedii: An In Vivo Study on Natural Aging Rat
      Model.
AB  - Traditional Chinese medicine (TCM) has been extensively applied as preferable
      herbal remedy for menopausal symptoms. In the present work, the potential of a
      TCM recipe named RRF, composed of Radix Astragali, Radix Angelicae Sinensis, and
      Folium Epimedii, was investigated on a natural aging rat model. After
      administration of RRF (141, 282, and 564 mg/kg/d), the circulated estradiol (E2)
      level increased accompanied by a reduction of serum follicle stimulating hormone
      (FSH). But no significant impact on serum lutenizing hormone (LH) level was
      observed. As a result of the E2-FSH-LH adjustment, the histomorphology
      degenerations of ovary, uterus, and vagina of the 11.5-month female rats were
      alleviated. And lumbar vertebrae trabecular microstructure was also restored
      under RRF exposure by means of increasing the trabecular area and area rate.
      Moreover, levels of hypothalamic dopamine (DA) and norepinephrine (NE) rallied
      significantly after RRF treatment. Results from our studies suggest that RRF
      possesses a positive regulation on the estrogen imbalance and neurotransmitter
      disorder, thereby restoring reproductive organ degeneration and skeleton
      deterioration. The above-mentioned benefits of RRF on the menopause syndromes
      recommend RRF as a potential candidate for the treatment of perimenopausal
      syndrome. 

PMID- 24454514
TI  - Chondroprotective Activity of Murraya exotica through Inhibiting beta -Catenin
      Signaling Pathway.
AB  - Osteoarthritis (OA) is a degenerative joint disease that affects millions of
      people. Currently, there is no effective drug treatment for it. The purpose of
      this study is to investigate the chondroprotective effects of Murraya exotica
      (L.) on OA. The rat OA models were duplicated to prepare for separating OA
      chondrocytes, synovial fluid (SF), and serum containing M. exotica (50 mg/kg, 100
      mg/kg, and 200 mg/kg), M. exotica showed the activity of decreasing the contents
      of TNF- alpha and IL-1 beta in SF and the chondrocyte apoptosis in a dose
      dependent manner. To investigate the probable mechanism, quantitative real-time
      polymerase chain reaction (qRT-PCR) and western blotting were used to determine
      gene expression and protein profiles, respectively. The results reveal that M.
      exotica can downregulate mRNA and protein expressions of beta -catenin and COX-2
      and reporter activity significantly. Conclusively, M. exotica exhibits
      antiapoptotic chondroprotective activity probably through inhibiting beta 
      catenin signaling. 

PMID- 24454515
TI  - Wen-pi-tang-Hab-Wu-ling-san, a Polyherbal Medicine, Attenuates ER Stress in 3T3
      L1 Preadipocytes by Promoting the Insulin Signaling Pathway.
AB  - The endoplasmic reticulum (ER) is an organelle that functions to synthesize,
      fold, and transport proteins. ER stress is a key link between type 2 diabetes
      (T2D), obesity, and insulin resistance. In this study, we investigated the effect
      of WHW on the ER stress response and the insulin signaling pathway in 3T3-L1
      preadipocytes. 3T3-L1 preadipocytes were differentiated into adipocytes, and ER
      stress was then induced by treatment with tunicamycin. ER stress-induced
      adipocytes were treated with different concentrations of WHW for 24 h. The
      expression of ER stress-related molecules such as X-box-binding protein-1 (XBP
      1), glucose-regulated protein 78 (GRP78), C/EBP-homologous protein 10 (CHOP10),
      and eukaryotic initiation factor 2 alpha (eIF2 alpha ) and signaling molecules
      such as phosphatidylinositol 3-kinase (PI3K), insulin receptor substrates-1 (IRS
      1), and c-Jun N-terminal protein kinase (JNK) were investigated. WHW
      significantly inhibited the expression of XBP-1, GRP78, CHOP10, and eIF2 alpha in
      ER stress-induced 3T3-L1 adipocytes. WHW also increased the PI3K expression and
      the IRS-1 phosphorylation but decreased the phosphorylation of JNK in ER stress
      induced 3T3-L1 adipocytes. Our results indicate that WHW inhibits ER stress in
      adipocytes by suppressing the expression of ER stress-mediated molecules and the
      insulin signaling pathway, suggesting that WHW may be an attractive therapeutic
      agent for managing T2D. 

PMID- 24454516
TI  - dTGS: Method for Effective Components Identification from Traditional Chinese
      Medicine Formula and Mechanism Analysis.
AB  - Because of the complexity of the components in Traditional Chinese Medicine
      formula (TCM formula), it is still a challenge to identify its effective
      components, to elucidate the mechanism of the components, and to discover the
      relationship between components and therapy objectives. In this paper, a method
      called directed TCM grammar systems (dTGS) for effective component identification
      was proposed using entity grammar systems (EGS) as the theoretical framework. The
      component-disease relationship of a TCM formula (i.e., Bai-Hu decoction plus
      Wasting-Thirsting formula, BHDWT) and one disease (i.e., type 2 diabetes
      mellitus) treated with it was studied, and the effective component groups (ECGs)
      were identified. 19 compounds were found acting on 20 proteins in type 2 diabetes
      mellitus (T2D) disease network, and 15 compounds were determined as the candidate
      effective components. Results indicated that this method can be used to identify
      the effective components and provide an innovative way to elucidate the molecular
      mechanism of TCM formulas. 

PMID- 24454517
TI  - The anxiolytic effect of aromatherapy on patients awaiting ambulatory surgery: a
      randomized controlled trial.
AB  - The aim of this study was to determine if aromatherapy could reduce preoperative
      anxiety in ambulatory surgery patients. A total of 109 preoperative patients were
      randomly assigned to experimental (bergamot essential oil) and control (water
      vapor) conditions and their responses to the State Trait Anxiety Inventory and
      vital signs were monitored. Patients were stratified by previous surgical
      experience, but that did not influence the results. All those exposed to bergamot
      essential oil aromatherapy showed a greater reduction in preoperative anxiety
      than those in the control groups. Aromatherapy may be a useful part of a holistic
      approach to reducing preoperative anxiety before ambulatory surgery. 

PMID- 24454518
TI  - Protective Effects of Shen-Yuan-Dan, a Traditional Chinese Medicine, against
      Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro.
AB  - Objectives. The study was to investigate the effects and mechanisms of Shen-Yuan
      Dan (SYD) pharmacological postconditioning on myocardial ischemia/reperfusion
      (I/R) injury. Methods. In the in vivo experiment, myocardial injury markers and
      histopathology staining were examined. In the in vitro experiment, cell viability
      and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assays and Hoechst 33342 fluorochrome
      staining. The protein expressions of Bcl-2 and Bax were determined by
      immunocytochemistry assay. Results. Both low and high doses of SYD protected
      myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH)
      and creatine kinase-MB (CK-MB) activity and malondialdehyde (MDA) content,
      increasing superoxide dismutase (SOD) activity and attenuating histopathology
      injury. Meanwhile, in the in vitro experiment, SYD promoted cell viability and
      inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to
      the normal level by SYD pharmacological postconditioning. In contrast, the Bax
      protein level was markedly reduced by SYD pharmacological postconditioning. These
      effects of SYD were inhibited by LY294002. Conclusions. The results of this study
      suggested that SYD pharmacological postconditioning has protective effects
      against myocardial I/R injury in both in vivo and in vitro models, which are
      related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway. 

PMID- 24454519
TI  - Evaluation of a clinically intuitive quality assurance method.
AB  - There is a pressing need for clinically intuitive quality assurance methods that
      report metrics of relevance to the likely impact on tumor control of normal
      tissue injury. This paper presents a preliminary investigation into the accuracy
      of a novel "transform method" which enables a clinically relevant analysis
      through dose-volume-histograms (DVHs) and dose overlays on the patient's CT data.
      The transform method was tested by inducing a series of known mechanical and
      delivery errors onto simulated 3D dosimetry measurements of six different head
      and-neck IMRT treatment plans. Accuracy was then examined through the comparison
      of the transformed patient dose distributions and the known actual patient dose
      distributions through dose-volume histograms and normalized dose difference
      analysis. Through these metrics, the transform method was found to be highly
      accurate in predicting measured patient dose distributions for these types of
      errors.

PMID- 24454520
TI  - How effective can optical-CT 3D dosimetry be without refractive fluid matching?
AB  - Achieving accurate optical CT 3D dosimetry without the use of viscous refractive
      index (RI) matching fluids would greatly increase convenience. Software has been
      developed to simulate optical CT 3D dosimetry for a range of scanning
      configurations including parallel-beam, point and converging light sources. For
      each configuration the efficacy of 3 refractive media were investigated: air,
      water, and a fluid closely matched to Presage (RI = 1.00, 1.33 and 1.49
      respectively). The results revealed that the useable radius of the dosimeter
      (i.e. where data was within 2% of truth) reduced to 68% for water-matching, and
      31% for dry-scanning in air. Point source incident ray geometry produced slightly
      more favourable results, although variation between the three geometries was
      relatively small. The required detector size however, increased by a factor six
      for dry-scanning, introducing cost penalties. For applications where dose
      information is not required in the periphery, some dry and low-viscous matching
      configurations may be feasible.

PMID- 24454521
TI  - How accurate is image guided radiation therapy (IGRT) delivered with a micro
      irradiator?
AB  - There is significant interest in delivering precisely targeted small-volume
      radiation treatments, in the pre-clinical setting, to study dose-volume
      relationships with tumor control and normal tissue damage. In this work we
      investigate the IGRT targeting accuracy of the XRad225Cx system from Precision x
      Ray using high resolution 3D dosimetry techniques. Initial results revealed a
      significant targeting error of about 2.4mm. This error was reduced to within
      0.5mm after the IGRT hardware and software had been recalibrated. The facility
      for 3D dosimetry was essential to gain a comprehensive understanding of the
      targeting error in 3D.

PMID- 24454522
TI  - Preliminary investigation and application of a novel deformable PRESAGE(r)
      dosimeter.
AB  - Deformable 3D dosimeters have potential applications in validating deformable
      dose mapping algorithms. This study evaluates a novel deformable PRESAGE(r)
      dosimeter and its application toward validating the deformable algorithm employed
      by VelocityAI. The deformable PRESAGE(r) dosimeter exhibited a linear dose
      response with a sensitivity of 0.0032 DeltaOD/(Gy/cm). Comparison of an
      experimental dosimeter irradiated with an MLC pencilbeam checkerboard pattern
      under lateral compression up to 27% to a non-deformed control dosimeter
      irradiated with the same pattern verified dose tracking under deformation. CTs of
      the experimental dosimeter prior to and during compression were exported into
      VelocityAI and used to map an Eclipse dose distribution calculated on the
      compressed dosimeter to its original shape. A comparison between the VelocityAI
      dose distribution and the distribution from the dosimeter showed field
      displacements up to 7.3 mm and up to a 175% difference in field dimensions. These
      results highlight the need for validating deformable dose mapping algorithms to
      ensure patient safety and quality of care.

PMID- 24454523
TI  - Towards comprehensive characterization of Cs-137 Seeds using PRESAGE(r) dosimetry
      with optical tomography.
AB  - We describe a method to directly measure the radial dose and anisotropy functions
      of brachytherapy sources using polyurethane based dosimeters read out with
      optical CT. We measured the radial dose and anisotropy functions for a Cs-137
      source using a PRESAGE(r) dosimeter (9.5cm diameter, 9.2cm height) with a 0.35cm
      channel drilled for source placement. The dosimeter was immersed in water and
      irradiated to 5.3Gy at 1cm. Pre- and post-irradiation optical CT scans were
      acquired with the Duke Large field of view Optical CT Scanner (DLOS) and dose was
      reconstructed with 0.5mm isotropic voxel size. The measured radial dose factor
      matched the published fit to within 3% for radii between 0.5-3.0cm, and the
      anisotropy function matched to within 4% except for theta near 0 degrees  and 180
      degrees  and radii >3cm. Further improvements in measurement accuracy may be
      achieved by optimizing dose, using the high dynamic range scanning capability of
      DLOS, and irradiating multiple dosimeters. Initial simulations indicate an 8 fold
      increase in dose is possible while still allowing sufficient light transmission
      during optical CT. A more comprehensive measurement may be achieved by increasing
      dosimeter size and flipping the source orientation between irradiations.

PMID- 24454524
TI  - Positive organizational behavior and safety in the offshore oil industry:
      Exploring the determinants of positive safety climate.
AB  - Much research has now documented the substantial influence of safety climate on a
      range of important outcomes in safety critical organizations, but there has been
      scant attention to the question of what factors might be responsible for positive
      or negative safety climate. The present paper draws from positive organizational
      behavior theory to test workplace and individual factors that may affect safety
      climate. Specifically, we explore the potential influence of authentic leadership
      style and psychological capital on safety climate and risk outcomes. Across two
      samples of offshore oil-workers and seafarers working on oil platform supply
      ships, structural equation modeling yielded results that support a model in which
      authentic leadership exerts a direct effect on safety climate, as well as an
      indirect effect via psychological capital. This study shows the importance of
      leadership qualities as well as psychological factors in shaping a positive work
      safety climate and lowering the risk of accidents.

PMID- 24454526
TI  - Analysis of visual appearance of retinal nerve fibers in high resolution fundus
      images: a study on normal subjects.
AB  - The retinal ganglion axons are an important part of the visual system, which can
      be directly observed by fundus camera. The layer they form together inside the
      retina is the retinal nerve fiber layer (RNFL). This paper describes results of a
      texture RNFL analysis in color fundus photographs and compares these results with
      quantitative measurement of RNFL thickness obtained from optical coherence
      tomography on normal subjects. It is shown that local mean value, standard
      deviation, and Shannon entropy extracted from the green and blue channel of
      fundus images are correlated with corresponding RNFL thickness. The linear
      correlation coefficients achieved values 0.694, 0.547, and 0.512 for respective
      features measured on 439 retinal positions in the peripapillary area from 23 eyes
      of 15 different normal subjects. 

PMID- 24454525
TI  - Learning from the Cardiologists and Developing Eluting Stents Targeting the Mtor
      Pathway for Pulmonary Application; A Future Concept for Tracheal Stenosis.
AB  - Tracheal stenosis due to either benign or malignant disease is a situation that
      the pulmonary physicians and thoracic surgeons have to cope in their everyday
      clinical practice. In the case where tracheal stenosis is caused due to
      malignancy mini-interventional interventions with laser, apc, cryoprobe, balloon
      dilation or with combination of more than one equipment and technique can be
      used. On the other hand, in the case of a benign disease such as; tracheomalacia
      the clinician can immediately upon diagnosis proceed to the stent placement. In
      both situations however; it has been observed that the stents induce formation of
      granuloma tissue in both or one end of the stent. Therefore a frequent evaluation
      of the patient is necessary, taking also into account the nature of the primary
      disease. Evaluation methodologies identifying different types and extent of the
      trachea stenosis have been previously published. However; we still do not have an
      effective adjuvant therapy to prevent granuloma tissue formation or prolong
      already treated granuloma lesions. There have been proposed many mechanisms which
      induce the abnormal growth of the local tissue, such as; local pressure, local
      stress, inflammation and vascular endothelial growth factor overexpression.
      Immunomodulatory agents inhibiting the mTOR pathway are capable of inhibiting the
      inflammatory cascade locally. In the current mini-review we will try to present
      the current knowledge of drug eluting stents inhibiting the mTOR pathway and
      propose a future application of these stents as a local anti-proliferative
      treatment.

PMID- 24454527
TI  - Coarse-grained multifractality analysis based on structure function measurements
      to discriminate healthy from distressed foetuses.
AB  - This paper proposes a combined coarse-grained multifractal method to discriminate
      between distressed and normal foetuses. The coarse-graining operation was
      performed by means of a coarse-grained procedure and the multifractal operation
      was based on a structure function. The proposed method was evaluated by one
      hundred recordings including eighty normal foetuses and twenty distressed
      foetuses. We found that it was possible to discriminate between distressed and
      normal foetuses using the Hurst exponent, singularity, and Holder spectra. 

PMID- 24454528
TI  - Accelerating Dynamic Cardiac MR imaging using structured sparse representation.
AB  - Compressed sensing (CS) has produced promising results on dynamic cardiac MR
      imaging by exploiting the sparsity in image series. In this paper, we propose a
      new method to improve the CS reconstruction for dynamic cardiac MRI based on the
      theory of structured sparse representation. The proposed method user the PCA
      subdictionaries for adaptive sparse representation and suppresses the sparse
      coding noise to obtain good reconstructions. An accelerated iterative shrinkage
      algorithm is used to solve the optimization problem and achieve a fast
      convergence rate. Experimental results demonstrate that the proposed method
      improves the reconstruction quality of dynamic cardiac cine MRI over the state-of
      the-art CS method. 

PMID- 24454529
TI  - Validation study methods for estimating odds ratio in 2 * 2 * J tables when
      exposure is misclassified.
AB  - BACKGROUND: Misclassification of exposure variables in epidemiologic studies may
      lead to biased estimation of parameters and loss of power in statistical
      inferences. In this paper, the inverse matrix method, as an efficient method of
      the correction of odds ratio for the misclassification of a binary exposure, was
      generalized to nondifferential misclassification and 2 * 2 * J tables. METHODS:
      Simple estimates for predictive values when misclassification is nondifferential
      are presented. Using them, we estimated the corrected log odds ratio and its
      variance for 2 * 2 * J tables, using the inverse matrix method. A two-step
      weighted likelihood method was also developed. Moreover, we compared the matrix
      and inverse matrix methods to the maximum likelihood (MLE) method using a
      simulation study. RESULTS: In all situations, the inverse matrix method proved to
      be more efficient than the matrix method. Matrix and inverse matrix methods for
      nondifferential situations are more efficient than differential
      misclassification. CONCLUSIONS: Although MLE is optimal among all of the methods,
      it is computationally difficult and requires programming. On the other hand, the
      inverse matrix method with a simple closed-form presents acceptable efficiency.

PMID- 24454530
TI  - Embryonic heart morphogenesis from confocal microscopy imaging and automatic
      segmentation.
AB  - Embryonic heart morphogenesis (EHM) is a complex and dynamic process where the
      heart transforms from a single tube into a four-chambered pump. This process is
      of great biological and clinical interest but is still poorly understood for two
      main reasons. On the one hand, the existing imaging modalities for investigating
      EHM suffered from either limited penetration depth or limited spatial resolution.
      On the other hand, current works typically adopted manual segmentation, which was
      tedious, subjective, and time consuming considering the complexity of developing
      heart geometry and the large size of images. In this paper, we propose to utilize
      confocal microscopy imaging with tissue optical immersion clearing technique to
      image the heart at different stages of development for EHM study. The imaging
      method is able to produce high spatial resolution images and achieve large
      penetration depth at the same time. Furthermore, we propose a novel convex active
      contour model for automatic image segmentation. The model has the ability to deal
      with intensity fall-off in depth which is characterized by confocal microscopy
      images. We acquired the images of embryonic quail hearts from day 6 to day 14 of
      incubation for EHM study. The experimental results were promising and provided us
      with an insight view of early heart growth pattern and also paved the road for
      data-driven heart growth modeling. 

PMID- 24454531
TI  - ModeLang: a new approach for experts-friendly viral infections modeling.
AB  - Computational modeling is an important element of systems biology. One of its
      important applications is modeling complex, dynamical, and biological systems,
      including viral infections. This type of modeling usually requires close
      cooperation between biologists and mathematicians. However, such cooperation
      often faces communication problems because biologists do not have sufficient
      knowledge to understand mathematical description of the models, and
      mathematicians do not have sufficient knowledge to define and verify these
      models. In many areas of systems biology, this problem has already been solved;
      however, in some of these areas there are still certain problematic aspects. The
      goal of the presented research was to facilitate this cooperation by designing
      seminatural formal language for describing viral infection models that will be
      easy to understand for biologists and easy to use by mathematicians and computer
      scientists. The ModeLang language was designed in cooperation with biologists and
      its computer implementation was prepared. Tests proved that it can be
      successfully used to describe commonly used viral infection models and then to
      simulate and verify them. As a result, it can make cooperation between biologists
      and mathematicians modeling viral infections much easier, speeding up
      computational verification of formulated hypotheses. 

PMID- 24454532
TI  - Mathematical model of dynamic protein interactions regulating p53 protein
      stability for tumor suppression.
AB  - In the field of cancer biology, numerous genes or proteins form extremely complex
      regulatory network, which determines cancer cell fate and cancer cell survival.
      p53 is a major tumor suppressor that is lost in more than 50% of human cancers.
      It has been well known that a variety of proteins regulate its protein stability,
      which is essential for its tumor suppressive function. It remains elusive how we
      could understand and target p53 stabilization process through network analysis.
      In this paper we discuss the use of random walk and stationary distribution to
      measure the compound effect of a network of genes or proteins. This method is
      applied to the network of nine proteins that influence the protein stability of
      p53 via regulating the interaction between p53 and its regulator MDM2. Our study
      identifies that some proteins such as HDAC1 in the network of p53 regulators may
      have more profound effects on p53 stability, agreeing with the established
      findings on HDAC1. This work shows the importance of using mathematical analysis
      to dissect the complexity of biology networks in cancer. 

PMID- 24454533
TI  - Quantitatively plotting the human face for multivariate data visualisation
      illustrated by health assessments using laboratory parameters.
AB  - OBJECTIVE: The purpose of this study was to describe a new data visualisation
      system by plotting the human face to observe the comprehensive effects of
      multivariate data. METHODS: The Graphics Device Interface (GDI+) in the Visual
      Studio.NET development platform was used to write a program that enables facial
      image parameters to be recorded, such as cropping and rotation, and can generate
      a new facial image according to Z values from sets of normal data (Z > 3 was
      still counted as 3). The measured clinical laboratory parameters related to
      health status were obtained from senile people, glaucoma patients, and fatty
      liver patients to illustrate the facial data visualisation system. RESULTS: When
      the eyes, nose, and mouth were rotated around their own axes at the same angle,
      the deformation effects were similar. The deformation effects for any abnormality
      of the eyes, nose, or mouth should be slightly higher than those for simultaneous
      abnormalities. The facial changes in the populations with different health
      statuses were significant compared with a control population. CONCLUSIONS: The
      comprehensive effects of multivariate may not equal the sum of each variable. The
      3Z facial data visualisation system can effectively distinguish people with poor
      health status from healthy people.

PMID- 24454534
TI  - Automated bone age assessment: motivation, taxonomies, and challenges.
AB  - Bone age assessment (BAA) of unknown people is one of the most important topics
      in clinical procedure for evaluation of biological maturity of children. BAA is
      performed usually by comparing an X-ray of left hand wrist with an atlas of known
      sample bones. Recently, BAA has gained remarkable ground from academia and
      medicine. Manual methods of BAA are time-consuming and prone to observer
      variability. This is a motivation for developing automated methods of BAA.
      However, there is considerable research on the automated assessment, much of
      which are still in the experimental stage. This survey provides taxonomy of
      automated BAA approaches and discusses the challenges. Finally, we present
      suggestions for future research. 

PMID- 24454536
TI  - Comparison of different EHG feature selection methods for the detection of
      preterm labor.
AB  - Numerous types of linear and nonlinear features have been extracted from the
      electrohysterogram (EHG) in order to classify labor and pregnancy contractions.
      As a result, the number of available features is now very large. The goal of this
      study is to reduce the number of features by selecting only the relevant ones
      which are useful for solving the classification problem. This paper presents
      three methods for feature subset selection that can be applied to choose the best
      subsets for classifying labor and pregnancy contractions: an algorithm using the
      Jeffrey divergence (JD) distance, a sequential forward selection (SFS) algorithm,
      and a binary particle swarm optimization (BPSO) algorithm. The two last methods
      are based on a classifier and were tested with three types of classifiers. These
      methods have allowed us to identify common features which are relevant for
      contraction classification. 

PMID- 24454535
TI  - Integrative genomics with mediation analysis in a survival context.
AB  - DNA copy number aberrations (DCNA) and subsequent altered gene expression
      profiles may have a major impact on tumor initiation, on development, and
      eventually on recurrence and cancer-specific mortality. However, most methods
      employed in integrative genomic analysis of the two biological levels, DNA and
      RNA, do not consider survival time. In the present note, we propose the adoption
      of a survival analysis-based framework for the integrative analysis of DCNA and
      mRNA levels to reveal their implication on patient clinical outcome with the
      prerequisite that the effect of DCNA on survival is mediated by mRNA levels. The
      specific aim of the paper is to offer a feasible framework to test the DCNA-mRNA
      survival pathway. We provide statistical inference algorithms for mediation based
      on asymptotic results. Furthermore, we illustrate the applicability of the method
      in an integrative genomic analysis setting by using a breast cancer data set
      consisting of 141 invasive breast tumors. In addition, we provide implementation
      in R. 

PMID- 24454537
TI  - Analyzing EEG of quasi-brain-death based on dynamic sample entropy measures.
AB  - To give a more definite criterion using electroencephalograph (EEG) approach on
      brain death determination is vital for both reducing the risks and preventing
      medical misdiagnosis. This paper presents several novel adaptive computable
      entropy methods based on approximate entropy (ApEn) and sample entropy (SampEn)
      to monitor the varying symptoms of patients and to determine the brain death. The
      proposed method is a dynamic extension of the standard ApEn and SampEn by
      introducing a shifted time window. The main advantages of the developed dynamic
      approximate entropy (DApEn) and dynamic sample entropy (DSampEn) are for real
      time computation and practical use. Results from the analysis of 35 patients (63
      recordings) show that the proposed methods can illustrate effectiveness and well
      performance in evaluating the brain consciousness states. 

PMID- 24454538
TI  - Generic properties of curvature sensing through vision and touch.
AB  - Generic properties of curvature representations formed on the basis of vision and
      touch were examined as a function of mathematical properties of curved objects.
      Virtual representations of the curves were shown on a computer screen for visual
      scaling by sighted observers (experiment 1). Their physical counterparts were
      placed in the two hands of blindfolded and congenitally blind observers for
      tactile scaling. The psychophysical data show that curvature representations in
      congenitally blind individuals, who never had any visual experience, and in
      sighted observers, who rely on vision most of the time, are statistically linked
      to the same mathematical properties of the curves. The perceived magnitude of
      object curvature, sensed through either vision or touch, is related by a
      mathematical power law, with similar exponents for the two sensory modalities, to
      the aspect ratio of the curves, a scale invariant geometric property. This
      finding supports biologically motivated models of sensory integration suggesting
      a universal power law for the adaptive brain control and balance of motor
      responses to environmental stimuli from any sensory modality. 

PMID- 24454539
TI  - Maximum equilibrium prevalence of mosquito-borne microparasite infections in
      humans.
AB  - To determine the maximum equilibrium prevalence of mosquito-borne microparasitic
      infections, this paper proposes a general model for vector-borne infections which
      is flexible enough to comprise the dynamics of a great number of the known
      diseases transmitted by arthropods. From equilibrium analysis, we determined the
      number of infected vectors as an explicit function of the model's parameters and
      the prevalence of infection in the hosts. From the analysis, it is also possible
      to derive the basic reproduction number and the equilibrium force of infection as
      a function of those parameters and variables. From the force of infection, we
      were able to conclude that, depending on the disease's structure and the model's
      parameters, there is a maximum value of equilibrium prevalence for each of the
      mosquito-borne microparasitic infections. The analysis is exemplified by the
      cases of malaria and dengue fever. With the values of the parameters chosen to
      illustrate those calculations, the maximum equilibrium prevalence found was 31%
      and 0.02% for malaria and dengue, respectively. The equilibrium analysis
      demonstrated that there is a maximum prevalence for the mosquito-borne
      microparasitic infections. 

PMID- 24454540
TI  - Phage display informatics.

PMID- 24454541
TI  - smoothHR: an R package for pointwise nonparametric estimation of hazard ratio
      curves of continuous predictors.
AB  - The Cox proportional hazards regression model has become the traditional choice
      for modeling survival data in medical studies. To introduce flexibility into the
      Cox model, several smoothing methods may be applied, and approaches based on
      splines are the most frequently considered in this context. To better understand
      the effects that each continuous covariate has on the outcome, results can be
      expressed in terms of splines-based hazard ratio (HR) curves, taking a specific
      covariate value as reference. Despite the potential advantages of using spline
      smoothing methods in survival analysis, there is currently no analytical method
      in the R software to choose the optimal degrees of freedom in multivariable Cox
      models (with two or more nonlinear covariate effects). This paper describes an R
      package, called smoothHR, that allows the computation of pointwise estimates of
      the HRs--and their corresponding confidence limits--of continuous predictors
      introduced nonlinearly. In addition the package provides functions for choosing
      automatically the degrees of freedom in multivariable Cox models. The package is
      available from the R homepage. We illustrate the use of the key functions of the
      smoothHR package using data from a study on breast cancer and data on acute
      coronary syndrome, from Galicia, Spain.

PMID- 24454542
TI  - Analysis of a single hemodialysis on phosphate removal of the internal fistula
      patients by mathematical and statistical methods.
AB  - Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide
      challenge in hemodialysis patients. In china, the number of dialysis patients is
      growing but few data are available about their bone disorders. In the current
      study, we aimed to evaluate the effect of clinical factors on the serum
      phosphorus clearance in the 80 maintenance hemodialysis (MHD) patients. Six
      clinical factors were identified for their association with the serum phosphorus
      clearance using the analysis of Spearman's single linear correlation, including
      predialysis serum phosphate level, CRR, membrane surface area of the dialyzer,
      effective blood flow rate, the blood chamber volume, and hematocrit. In an
      overall multivariate analysis, pre-P, CRR, membrane SA, and Qb were identified as
      independent risk factors associated with the serum phosphorus clearance. In
      conclusion, HD could effectively clear serum phosphorus. The analysis of CRR
      might help to estimate serum phosphorus reduction ratio. 

PMID- 24454543
TI  - Nanoinformatics workshop report: Current resources, community needs, and the
      proposal of a collaborative framework for data sharing and information
      integration.
AB  - The quantity of information on nanomaterial properties and behavior continues to
      grow rapidly. Without a concerted effort to collect, organize and mine disparate
      information coming out of current research efforts, the value and effective use
      of this information will be limited at best. Data will not be translated to
      knowledge. At worst, erroneous conclusions will be drawn and future research may
      be misdirected. Nanoinformatics can be a powerful approach to enhance the value
      of global information in nanoscience and nanotechnology. Much progress has been
      made through grassroots efforts in nanoinformatics resulting in a multitude of
      resources and tools for nanoscience researchers. In 2012, the nanoinformatics
      community believed it was important to critically evaluate and refine currently
      available nanoinformatics approaches in order to best inform the science and
      support the future of predictive nanotechnology. The Greener Nano 2012:
      Nanoinformatics Tools and Resources Workshop brought together informatics groups
      with materials scientists active in nanoscience research to evaluate and reflect
      on the tools and resources that have recently emerged in support of predictive
      nanotechnology. The workshop goals were to establish a better understanding of
      current nanoinformatics approaches and to clearly define immediate and projected
      informatics infrastructure needs of the nanotechnology community. The theme of
      nanotechnology environmental health and safety (nanoEHS) was used to provide real
      world, concrete examples on how informatics can be utilized to advance our
      knowledge and guide nanoscience. The benefit here is that the same properties
      that impact the performance of products could also be the properties that inform
      EHS. From a decision management standpoint, the dual use of such data should be
      considered a priority. Key outcomes include a proposed collaborative framework
      for data collection, data sharing and information integration.

PMID- 24454544
TI  - Climate change, adaptation, and phenotypic plasticity: the problem and the
      evidence.
AB  - Many studies have recorded phenotypic changes in natural populations and
      attributed them to climate change. However, controversy and uncertainty has
      arisen around three levels of inference in such studies. First, it has proven
      difficult to conclusively distinguish whether phenotypic changes are genetically
      based or the result of phenotypic plasticity. Second, whether or not the change
      is adaptive is usually assumed rather than tested. Third, inferences that climate
      change is the specific causal agent have rarely involved the testing - and
      exclusion - of other potential drivers. We here review the various ways in which
      the above inferences have been attempted, and evaluate the strength of support
      that each approach can provide. This methodological assessment sets the stage for
      11 accompanying review articles that attempt comprehensive syntheses of what is
      currently known - and not known - about responses to climate change in a variety
      of taxa and in theory. Summarizing and relying on the results of these reviews,
      we arrive at the conclusion that evidence for genetic adaptation to climate
      change has been found in some systems, but is still relatively scarce. Most
      importantly, it is clear that more studies are needed - and these must employ
      better inferential methods - before general conclusions can be drawn. Overall, we
      hope that the present paper and special issue provide inspiration for future
      research and guidelines on best practices for its execution. 

PMID- 24454545
TI  - Climate change and timing of avian breeding and migration: evolutionary versus
      plastic changes.
AB  - There are multiple observations around the globe showing that in many avian
      species, both the timing of migration and breeding have advanced, due to warmer
      springs. Here, we review the literature to disentangle the actions of
      evolutionary changes in response to selection induced by climate change versus
      changes due to individual plasticity, that is, the capacity of an individual to
      adjust its phenology to environmental variables. Within the abundant literature
      on climate change effects on bird phenology, only a small fraction of studies are
      based on individual data, yet individual data are required to quantify the
      relative importance of plastic versus evolutionary responses. While plasticity
      seems common and often adaptive, no study so far has provided direct evidence for
      an evolutionary response of bird phenology to current climate change. This
      assessment leads us to notice the alarming lack of tests for microevolutionary
      changes in bird phenology in response to climate change, in contrast with the
      abundant claims on this issue. In short, at present we cannot draw reliable
      conclusions on the processes underlying the observed patterns of advanced
      phenology in birds. Rapid improvements in techniques for gathering and analysing
      individual data offer exciting possibilities that should encourage research
      activity to fill this knowledge gap. 

PMID- 24454546
TI  - Climate change and mammals: evolutionary versus plastic responses.
AB  - Phenotypic plasticity and microevolution are the two primary means by which
      organisms respond adaptively to local conditions. While these mechanisms are not
      mutually exclusive, their relative magnitudes will influence both the rate of,
      and ability to sustain, phenotypic responses to climate change. We review
      accounts of recent phenotypic changes in wild mammal populations with the purpose
      of critically evaluating the following: (i) whether climate change has been
      identified as the causal mechanism producing the observed change; (ii) whether
      the change is adaptive; and (iii) the relative influences of evolution and/or
      phenotypic plasticity underlying the change. The available data for mammals are
      scant. We found twelve studies that report changes in phenology, body weight or
      litter size. In all cases, the observed response was primarily due to plasticity.
      Only one study (of advancing parturition dates in American red squirrels)
      provided convincing evidence of contemporary evolution. Subsequently, however,
      climate change has been shown to not be the causal mechanism underlying this
      shift. We also summarize studies that have shown evolutionary potential (i.e. the
      trait is heritable and/or under selection) in traits with putative associations
      with climate change and discuss future directions that need to be undertaken
      before a conclusive demonstration of plastic or evolutionary responses to climate
      change in wild mammals can be made. 

PMID- 24454547
TI  - Evolutionary and plastic responses of freshwater invertebrates to climate change:
      realized patterns and future potential.
AB  - We integrated the evidence for evolutionary and plastic trait changes in situ in
      response to climate change in freshwater invertebrates (aquatic insects and
      zooplankton). The synthesis on the trait changes in response to the expected
      reductions in hydroperiod and increases in salinity indicated little evidence for
      adaptive, plastic, and genetic trait changes and for local adaptation. With
      respect to responses to temperature, there are many studies on temporal trait
      changes in phenology and body size in the wild that are believed to be driven by
      temperature increases, but there is a general lack of rigorous demonstration
      whether these trait changes are genetically based, adaptive, and causally driven
      by climate change. Current proof for genetic trait changes under climate change
      in freshwater invertebrates stems from a limited set of common garden experiments
      replicated in time. Experimental thermal evolution experiments and common garden
      warming experiments associated with space-for-time substitutions along
      latitudinal gradients indicate that besides genetic changes, also phenotypic
      plasticity and evolution of plasticity are likely to contribute to the observed
      phenotypic changes under climate change in aquatic invertebrates. Apart from
      plastic and genetic thermal adjustments, also genetic photoperiod adjustments are
      widespread and may even dominate the observed phenological shifts. 

PMID- 24454548
TI  - Contemporary climate change and terrestrial invertebrates: evolutionary versus
      plastic changes.
AB  - To forecast the responses of species to future climate change, an understanding
      of the ability of species to adapt to long-term shifts in temperature is crucial.
      We present a review on evolutionary adaptation and phenotypic plasticity of
      temperature-related traits in terrestrial invertebrates. The evidence for
      adaptive evolution in melanization is good, but we caution that genetic
      determination needs to be tested in each individual species, and complex genetic
      correlations may exist. For phenological traits allochronic data sets provide
      powerful means to track climate-induced changes; however, rarely are responses
      deconstructed into evolutionary and plastic responses. Laboratory studies suggest
      climate change responses in these traits will be driven by both. For stress
      resistance, the evidence for shifts in traits is poor. Studies leaning heavily on
      Drosophila have demonstrated potential limits to evolutionary responses in
      desiccation and heat resistance. Quantifying the capacity for these species to
      respond plastically and extending this work to other taxa will be an important
      next step. We also note that, although not strictly speaking a species trait, the
      response of endosymbionts to heat stress requires further study. Finally, while
      clearly genetic, and possibly adaptive, the anonymous nature of latitudinal
      shifts in clines of genetic markers in Drosophila prevents further
      interpretation. 

PMID- 24454549
TI  - Plastic and evolutionary responses to climate change in fish.
AB  - The physical and ecological 'fingerprints' of anthropogenic climate change over
      the past century are now well documented in many environments and taxa. We
      reviewed the evidence for phenotypic responses to recent climate change in fish.
      Changes in the timing of migration and reproduction, age at maturity, age at
      juvenile migration, growth, survival and fecundity were associated primarily with
      changes in temperature. Although these traits can evolve rapidly, only two
      studies attributed phenotypic changes formally to evolutionary mechanisms. The
      correlation-based methods most frequently employed point largely to 'fine
      grained' population responses to environmental variability (i.e. rapid phenotypic
      changes relative to generation time), consistent with plastic mechanisms.
      Ultimately, many species will likely adapt to long-term warming trends overlaid
      on natural climate oscillations. Considering the strong plasticity in all traits
      studied, we recommend development and expanded use of methods capable of
      detecting evolutionary change, such as the long term study of selection
      coefficients and temporal shifts in reaction norms, and increased attention to
      forecasting adaptive change in response to the synergistic interactions of the
      multiple selection pressures likely to be associated with climate change. 

PMID- 24454550
TI  - Plasticity and genetic adaptation mediate amphibian and reptile responses to
      climate change.
AB  - Phenotypic plasticity and genetic adaptation are predicted to mitigate some of
      the negative biotic consequences of climate change. Here, we evaluate evidence
      for plastic and evolutionary responses to climate variation in amphibians and
      reptiles via a literature review and meta-analysis. We included studies that
      either document phenotypic changes through time or space. Plasticity had a clear
      and ubiquitous role in promoting phenotypic changes in response to climate
      variation. For adaptive evolution, we found no direct evidence for evolution of
      amphibians or reptiles in response to climate change over time. However, we found
      many studies that documented adaptive responses to climate along spatial
      gradients. Plasticity provided a mixture of adaptive and maladaptive responses to
      climate change, highlighting that plasticity frequently, but not always, could
      ameliorate climate change. Based on our review, we advocate for more experiments
      that survey genetic changes through time in response to climate change. Overall,
      plastic and genetic variation in amphibians and reptiles could buffer some of the
      formidable threats from climate change, but large uncertainties remain owing to
      limited data. 

PMID- 24454551
TI  - Climate change in the oceans: evolutionary versus phenotypically plastic
      responses of marine animals and plants.
AB  - I summarize marine studies on plastic versus adaptive responses to global change.
      Due to the lack of time series, this review focuses largely on the potential for
      adaptive evolution in marine animals and plants. The approaches were mainly
      synchronic comparisons of phenotypically divergent populations, substituting
      spatial contrasts in temperature or CO2 environments for temporal changes, or in
      assessments of adaptive genetic diversity within populations for traits important
      under global change. The available literature is biased towards gastropods,
      crustaceans, cnidarians and macroalgae. Focal traits were mostly environmental
      tolerances, which correspond to phenotypic buffering, a plasticity type that
      maintains a functional phenotype despite external disturbance. Almost all studies
      address coastal species that are already today exposed to fluctuations in
      temperature, pH and oxygen levels. Recommendations for future research include
      (i) initiation and analyses of observational and experimental temporal studies
      encompassing diverse phenotypic traits (including diapausing cues, dispersal
      traits, reproductive timing, morphology) (ii) quantification of nongenetic trans
      generational effects along with components of additive genetic variance (iii)
      adaptive changes in microbe-host associations under the holobiont model in
      response to global change (iv) evolution of plasticity patterns under
      increasingly fluctuating environments and extreme conditions and (v) joint
      consideration of demography and evolutionary adaptation in evolutionary rescue
      approaches. 

PMID- 24454552
TI  - Evolutionary and plastic responses to climate change in terrestrial plant
      populations.
AB  - As climate change progresses, we are observing widespread changes in phenotypes
      in many plant populations. Whether these phenotypic changes are directly caused
      by climate change, and whether they result from phenotypic plasticity or
      evolution, are active areas of investigation. Here, we review terrestrial plant
      studies addressing these questions. Plastic and evolutionary responses to climate
      change are clearly occurring. Of the 38 studies that met our criteria for
      inclusion, all found plastic or evolutionary responses, with 26 studies showing
      both. These responses, however, may be insufficient to keep pace with climate
      change, as indicated by eight of 12 studies that examined this directly. There is
      also mixed evidence for whether evolutionary responses are adaptive, and whether
      they are directly caused by contemporary climatic changes. We discuss factors
      that will likely influence the extent of plastic and evolutionary responses,
      including patterns of environmental changes, species' life history
      characteristics including generation time and breeding system, and degree and
      direction of gene flow. Future studies with standardized methodologies,
      especially those that use direct approaches assessing responses to climate change
      over time, and sharing of data through public databases, will facilitate better
      predictions of the capacity for plant populations to respond to rapid climate
      change. 

PMID- 24454553
TI  - Evolutionary potential of marine phytoplankton under ocean acidification.
AB  - Marine phytoplankton have many obvious characters, such as rapid cell division
      rates and large population sizes, that give them the capacity to evolve in
      response to global change on timescales of weeks, months or decades. However, few
      studies directly investigate if this adaptive potential is likely to be realized.
      Because of this, evidence of to whether and how marine phytoplankton may evolve
      in response to global change is sparse. Here, we review studies that help predict
      evolutionary responses to global change in marine phytoplankton. We find limited
      support from experimental evolution that some taxa of marine phytoplankton may
      adapt to ocean acidification, and strong indications from studies of variation
      and structure in natural populations that selection on standing genetic variation
      is likely. Furthermore, we highlight the large body of literature on plastic
      responses to ocean acidification available, and evolutionary theory that may be
      used to link plastic and evolutionary responses. Because of the taxonomic breadth
      spanned by marine phytoplankton, and the diversity of roles they fill in ocean
      ecosystems and biogeochemical cycles, we stress the necessity of treating taxa or
      functional groups individually. 

PMID- 24454554
TI  - Climate warming and Bergmann's rule through time: is there any evidence?
AB  - Climate change is expected to induce many ecological and evolutionary changes.
      Among these is the hypothesis that climate warming will cause a reduction in body
      size. This hypothesis stems from Bergmann's rule, a trend whereby species exhibit
      a smaller body size in warmer climates, and larger body size under colder
      conditions in endotherms. The mechanisms behind this rule are still debated, and
      it is not clear whether Bergmann's rule can be extended to predict the effects of
      climate change through time. We reviewed the primary literature for evidence (i)
      of a decrease in body size in response to climate warming, (ii) that changing
      body size is an adaptive response and (iii) that these responses are evolutionary
      or plastic. We found weak evidence for changes in body size through time as
      predicted by Bergmann's rule. Only three studies investigated the adaptive nature
      of these size decreases. Of these, none reported evidence of selection for
      smaller size or of a genetic basis for the size change, suggesting that size
      decreases could be due to nonadaptive plasticity in response to changing
      environmental conditions. More studies are needed before firm conclusions can be
      drawn about the underlying causes of these changes in body size in response to a
      warming climate. 

PMID- 24454557
TI  - Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl)
      3H-1lambda(3),2-benziodaoxol-3-one.
AB  - The synthesis of 5-nitro-1-(trifluoromethyl)-3H-1lambda(3),2-benziodaoxol-3-one
      (3), a hypervalent-iodine-based electrophilic trifluoromethylating reagent, is
      described. Whereas considerations based on cyclic voltammetry and X-ray
      structural properties would predict an inferior reactivity when compared to the
      non-nitrated derivative 2, (19)F NMR kinetic studies showed that this new
      derivative is almost one order of magnitude more reactive. Furthermore,
      differential scanning calorimetry measurements indicated that, in addition, it is
      also safer to handle. 

PMID- 24454555
TI  - Rapid evolution of quantitative traits: theoretical perspectives.
AB  - An increasing number of studies demonstrate phenotypic and genetic changes in
      natural populations that are subject to climate change, and there is hope that
      some of these changes will contribute to avoiding species extinctions
      ('evolutionary rescue'). Here, we review theoretical models of rapid evolution in
      quantitative traits that can shed light on the potential for adaptation to a
      changing climate. Our focus is on quantitative-genetic models with selection for
      a moving phenotypic optimum. We point out that there is no one-to-one
      relationship between the rate of adaptation and population survival, because the
      former depends on relative fitness and the latter on absolute fitness.
      Nevertheless, previous estimates that sustainable rates of genetically based
      change usually do not exceed 0.1 haldanes (i.e., phenotypic standard deviations
      per generation) are probably correct. Survival can be greatly facilitated by
      phenotypic plasticity, and heritable variation in plasticity can further speed up
      genetic evolution. Multivariate selection and genetic correlations are frequently
      assumed to constrain adaptation, but this is not necessarily the case and depends
      on the geometric relationship between the fitness landscape and the structure of
      genetic variation. Similar conclusions hold for adaptation to shifting spatial
      gradients. Recent models of adaptation in multispecies communities indicate that
      the potential for rapid evolution is strongly influenced by interspecific
      competition. 

PMID- 24454558
TI  - Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as
      tools for epigenetics.
AB  - In this work we present for the first time the synthesis of novel 5
      hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) derivatives that can be
      used as tools in the emerging field of epigenetics for deciphering chemical
      biology of TET-mediated processes. 

PMID- 24454559
TI  - Studies on the interaction of isocyanides with imines: reaction scope and
      mechanistic variations.
AB  - The interaction of imines with isocyanides has been studied. The main product
      results from a sequential process involving the attack of two units of
      isocyanide, under Lewis acid catalysis, upon the carbon-nitrogen double bond of
      the imine to form the 4-membered ring system. The scope of the reaction regarding
      the imine and isocyanide ranges has been determined, and also some mechanistic
      variations and structural features have been described. 

PMID- 24454560
TI  - The difluoromethylene (CF2) group in aliphatic chains: Synthesis and
      conformational preference of palmitic acids and nonadecane containing CF2 groups.
AB  - The syntheses of palmitic acids and a nonadecane are reported with CF2 groups
      located 1,3 or 1,4 to each other along the aliphatic chain. Specifically
      8,8,10,10- and 8,8,11,11-tetrafluorohexadecanoic acids (6b and 6c) are prepared
      as well as the singly modified analogue 8,8-difluorohexadecanoic acid (6a). Also
      8,8,11,11-tetrafluorononadecane (27) is prepared as a pure hydrocarbon containing
      a 1,4-di-CF2 motif. The modified palmitic acids are characterized by differential
      scanning calorimetry (DSC) to determine melting points and phase behaviour
      relative to palmitic acid (62.5  degrees C). It emerges that 6c, with the CF2
      groups placed 1,4- to each other, has a significantly higher melting point (89.9 
      degrees C) when compared to the other analogues and palmitic acid itself. It is a
      crystalline compound and the structure reveals an extended anti-zig-zag chain.
      Similarly 8,8,11,11-tetrafluorononadecane (27) adopts an extended anti-zig-zag
      structure. This is rationalized by dipolar relaxation between the two CF2 groups
      placed 1,4 to each other in the extended anti-zig-zag chain and suggests a design
      modification for long chain aliphatics which can introduce conformational
      stability. 

PMID- 24454561
TI  - Silica: An efficient catalyst for one-pot regioselective synthesis of
      dithioethers.
AB  - The development of a silica-promoted highly selective synthesis of 1,2 or 1,3
      dithioethers via solvent-free one-pot tandem reactions of an allyl bromide with
      excess thiol at room temperature is described. The choice of silica gel, either
      pre-calcined or moistened with water, exhibited notable regioselectivity in the
      formation of dithioethers. Plausible mechanistic routes were explored and
      postulated. 

PMID- 24454563
TI  - Multicomponent reactions II.

PMID- 24454564
TI  - The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via
      three-component reactions of acrylamides and aroylacrylic acids with isatins and
      alpha-amino acids.
AB  - The regioselective three-component condensation of azomethine ylides derived from
      isatins and alpha-amino acids with acrylamides or aroylacrylic acids as
      dipolarophiles has been realized through a one-pot 1,3-dipolar cycloaddition
      protocol. Decarboxylation of 2'-aroyl-2-oxo-1,1',2,2',5',6',7',7a'
      octahydrospiro[indole-3,3'-pyrrolizine]-1'-carboxylic acids is accompanied by
      cyclative rearrangement with formation of dihydropyrrolizinyl indolones. 

PMID- 24454565
TI  - Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis
      Hillman adduct: A unified biomimetic approach.
AB  - A unified strategy was followed for the synthesis of three putrescine bisamides,
      (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia
      gigantea, by making use of a common synthetic intermediate prepared by the Baylis
      Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was
      accomplished from camphor sultam. 

PMID- 24454566
TI  - Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1-DNA
      complex formation.
AB  - Hedgehog (Hh) signaling plays an important role in embryonic development, cell
      maintenance and cell proliferation. Moreover, Hh signaling contributes to the
      growth of cancer cells. Physalins are highly oxidized natural products with a
      complex structure. Physalins (1-7) were isolated from Solanum nigrum (Solanaceae)
      collected in Bangladesh by using our cell-based assay. The isolated physalins
      included the previously reported Hh inhibitors 5 and 6. Compounds 1 and 4 showed
      strong inhibition of GLI1 transcriptional activity, and exhibited cytotoxicity
      against cancer cell lines with an aberrant activation of Hh signaling. Compound 1
      inhibited the production of the Hh-related proteins patched (PTCH) and BCL2.
      Analysis of the structures of different physalins showed that the left part of
      the physalins was important for Hh inhibitory activity. Interestingly, physalin H
      (1) disrupted GLI1 binding to its DNA binding domain, while the weak inhibitor
      physalin G (2) did not show inhibition of GLI1-DNA complex formation. 

PMID- 24454567
TI  - Organobase-catalyzed three-component reactions for the synthesis of 4H-2
      aminopyrans, condensed pyrans and polysubstituted benzenes.
AB  - Novel routes for the preparation of 2-amino-4H-pyran-3-carbonitrile 9, amino
      arylbenzoic acid ester derivatives 13a,b, 2-aminotetrahydro-4H-chromene-3
      carbonitrile 18, 3-amino-4-cyanotetrahydronaphthalene-2-carboxylic acid ester 26
      and 4-amino-3,5-dicyanophthalic acid ester derivatives 37a-c were developed. The
      synthetic methods utilize one-pot reactions of acetylene carboxylic acid esters,
      alpha,beta-unsaturated nitriles and/or active methylenenitriles in the presence
      of L-proline or DABCO. Plausible mechanisms are suggested for the formation of
      the products. Finally, these compounds were used for the efficient synthesis of 6
      amino-5-cyanonicotinic acid ester derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3
      d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9
      carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3-oxo-5-phenyl-3H
      isoindole-4-carboxylate (40). 

PMID- 24454562
TI  - Synthesis of five- and six-membered cyclic organic peroxides: Key transformations
      into peroxide ring-retaining products.
AB  - The present review describes the current status of synthetic five and six
      membered cyclic peroxides such as 1,2-dioxolanes, 1,2,4-trioxolanes (ozonides),
      1,2-dioxanes, 1,2-dioxenes, 1,2,4-trioxanes, and 1,2,4,5-tetraoxanes. The
      literature from 2000 onwards is surveyed to provide an update on synthesis of
      cyclic peroxides. The indicated period of time is, on the whole, characterized by
      the development of new efficient and scale-up methods for the preparation of
      these cyclic compounds. It was shown that cyclic peroxides remain unchanged
      throughout the course of a wide range of fundamental organic reactions. Due to
      these properties, the molecular structures can be greatly modified to give
      peroxide ring-retaining products. The chemistry of cyclic peroxides has attracted
      considerable attention, because these compounds are used in medicine for the
      design of antimalarial, antihelminthic, and antitumor agents. 

PMID- 24454568
TI  - One-pot synthesis of cyanohydrin derivatives from alkyl bromides via
      incorporation of two one-carbon components by consecutive radical/ionic
      reactions.
AB  - The consecutive radical/ionic reaction consisting of radical formylation of alkyl
      bromides and nucleophilic addition of a cyanide ion was investigated, which gave
      moderate to good yields of cyanohydrin derivatives in one-pot. 

PMID- 24454569
TI  - Synthesis and biological activity of N-substituted-tetrahydro-gamma-carbolines
      containing peptide residues.
AB  - The synthesis of novel peptide conjugates of N-substituted-tetrahydro-gamma
      carbolines has been performed using the sequence of the Ugi multicomponent
      reaction and Cu(I)-catalyzed click chemistry. The effect of obtained gamma
      carboline-peptide conjugates on the rat liver mitochondria was evaluated. It was
      found that all compounds in the concentration of 30 uM did onot induce
      depolarization of mitochondria but possessed some inhibitory effect on the
      mitochondria permeability transition. The original N-substituted-tetrahydro-gamma
      carbolines containing an terminal alkyne group demonstrated a high prooxidant
      activity, whereas their conjugates with peptide fragments slightly inhibited both
      autooxidation and the t-BHP-induced lipid peroxidation. 

PMID- 24454570
TI  - A unified approach to the important protein kinase inhibitor balanol and a
      proposed analogue.
AB  - A common approach to the important protein kinase inhibitor (-)-balanol and an
      azepine-ring-modified balanol derivative has been developed using an efficient
      fragment coupling protocol which proceeded in good overall yield. 

PMID- 24454571
TI  - Studies toward bivalent kappa opioids derived from salvinorin A:
      heteromethylation of the furan ring reduces affinity.
AB  - The recent crystal structure of the kappa-opioid receptor (kappa-OR) revealed,
      unexpectedly, that the antagonist JDTic is a bivalent ligand: in addition to the
      orthosteric pocket occupied by morphinans, JDTic also occupies a distinct
      (allotopic) pocket. Mutagenesis data suggest that salvinorin A (1) also binds to
      this allotopic pocket, adjacent to the aspartate residue that anchors the basic
      nitrogen atom of classical opiates (Asp138). It has been suggested that an H-bond
      donor appended to 1 might interact with Asp138, increasing affinity. Such a
      bivalent ligand might also possess altered functional selectivity. Based on
      modeling and known N-furanylmethyl opioid antagonists, we appended H-bond donors
      to the furan ring of 1. (Dimethylamino)methyl groups at C-15 or C-16 abolished
      affinity for kappa-OR. Hydroxymethylation at C-16 was tolerated, but 15,16-bis
      hydroxymethylation was not. Since allosteric modulators may go undetected in
      binding assays, we also tested these and other low-affinity derivatives of 1 for
      allosteric modulation of dynorphin A in the [(35)S]GTPgammaS assay. No modulation
      was detected. As an alternative attachment point for bivalent derivatives, we
      prepared the 2-(hydroxyethoxy)methyl ether, which retained high affinity for
      kappa-OR. We discuss alternative design strategies for linked, fused or merged
      bivalent derivatives of 1. 

PMID- 24454572
TI  - Synthesis and determination of the absolute configuration of (-)-(5R,6Z)
      dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni.
AB  - A small sample of (-)-(5R,6Z)-dendrolasin-5-acetate, which was fully
      characterized by 2D NMR studies, was isolated from the nudibranch Hypselodoris
      jacksoni, along with the sesquiterpenes (+)-agassizin, (-)-furodysinin, (-)
      euryfuran, (-)-dehydroherbadysidolide and (+)-pallescensone. A synthetic sample
      ([alpha]D -8.7) of the new metabolite was prepared by [1,2]-Wittig rearrangement
      of a geranylfuryl ether followed by acetylation of purified alcohol isomers. The
      absolute configuration at C-5 was established as R by the analysis of MPA ester
      derivatives of (Z)-5-hydroxydendrolasin obtained by preparative enantioselective
      HPLC. 

PMID- 24454573
TI  - Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic
      aldehydes and acetylenedicarboxylate.
AB  - The four-component reaction of 2-aminobenzothiazole, aromatic aldehydes,
      acetylenedicarboxylate and piperidine or pyrrolidine in ethanol afforded the
      functionalized 2-pyrrolidinones containing both benzothiazolyl and piperidinyl
      (or pyrrolidinyl) units in good yields. On the other hand, the similar four
      component reactions resulted in the functionalized morpholinium or piperidinium 2
      pyrrolidinon-3-olates in the presence of p-toluenesulfonic acid. 

PMID- 24454574
TI  - Plakilactones G and H from a marine sponge. Stereochemical determination of
      highly flexible systems by quantitative NMR-derived interproton distances
      combined with quantum mechanical calculations of (13)C chemical shifts.
AB  - In this paper the stereostructural investigation of two new oxygenated
      polyketides, plakilactones G and H, isolated from the marine sponge
      Plakinastrella mamillaris collected at Fiji Islands, is reported. The
      stereostructural studies began on plakilactone H by applying an integrated
      approach of the NOE-based protocol and quantum mechanical calculations of (13)C
      chemical shifts. In particular, plakilactone H was used as a template to extend
      the application of NMR-derived interproton distances to a highly flexible
      molecular system with simultaneous assignment of four non-contiguous
      stereocenters. Chemical derivatization and quantum mechanical calculations of
      (13)C on plakilactone G along with a plausible biogenetic interconversion between
      plakilactone G and plakilactone H allowed us to determine the absolute
      configuration in this two new oxygenated polyketides. 

PMID- 24454575
TI  - Decay of references to Web sites in articles published in general medical
      journals: mainstream vs small journals.
AB  - BACKGROUND: Over the last decade, Web sites (URLs) have been increasingly cited
      in scientific articles. However, the contents of the page of interest may change
      over the time. OBJECTIVE: To investigate the trend of citation to URLs in five
      general medical journals since January 2006 to June 2013 and to compare the
      trends in mainstream journals with small journals. METHODS: References of all
      original articles and review articles published between January 2006 and June
      2013 in three regional journals - Archives of Iranian Medicine (AIM), Eastern
      Mediterranean Health Journal (EMHJ), and Journal of Postgraduate Medical
      Institute (JPMI) - and two mainstream journals - The Lancet and British Medical
      Journal (BMJ) - were reviewed. The references were checked to determine the
      frequency of citation to URLs as well as the rate of accessibility of the URLs
      cited. RESULTS: A total of 2822 articles was studied. Since January 2006 onward,
      the number of citations to URLs increased in the journals (doubling time ranged
      from 4.2 years in EMHJ to 13.9 years in AIM). Overall, the percentage of articles
      citing at least one URL has increased from 24% in 2006 to 48.5% in 2013.
      Accessibility to URLs decayed as the references got old (half life ranged from
      2.2 years in EMHJ to 5.3 years in BMJ). The ratio of citation to URLs in the
      studied mainstream journals, as well as the ratio of URLs accessible were
      significantly (p<0.001) higher than the small medical journals. CONCLUSION: URLs
      are increasingly cited, but their contents decay with time. The trend of citing
      and decaying URLs are different in mainstream journals compared to small medical
      journals. Decay of URL contents would jeopardize the accuracy of the references
      and thus, the body of evidence. One way to tackle this important obstacle is to
      archive URLs permanently.

PMID- 24454576
TI  - Contributors to frequent telehealth alerts including false alerts for patients
      with heart failure: a mixed methods exploration.
AB  - BACKGROUND: Telehealth data overload through high alert generation is a
      significant barrier to sustained adoption of telehealth for managing HF patients.
      OBJECTIVE: To explore the factors contributing to frequent telehealth alerts
      including false alerts for Medicare heart failure (HF) patients admitted to a
      home health agency. MATERIALS AND METHODS: A mixed methods design that combined
      quantitative correlation analysis of patient characteristic data with number of
      telehealth alerts and qualitative analysis of telehealth and visiting nurses'
      notes on follow-up actions to patients' telehealth alerts was employed. All the
      quantitative and qualitative data was collected through retrospective review of
      electronic records of the home heath agency. RESULTS: Subjects in the study had a
      mean age of 83 (SD = 7.6); 56% were female. Patient co-morbidities (p<0.05) of
      renal disorders, anxiety, and cardiac arrhythmias emerged as predictors of
      telehealth alerts through quantitative analysis (n = 168) using multiple
      regression. Inappropriate telehealth measurement technique by patients (54%) and
      home healthcare system inefficiencies (37%) contributed to most telehealth false
      alerts in the purposive qualitative sub-sample (n = 35) of patients with high
      telehealth alerts. CONCLUSION: Encouraging patient engagement with the telehealth
      process, fostering a collaborative approach among all the clinicians involved
      with the telehealth intervention, tailoring telehealth alert thresholds to
      patient characteristics along with establishing patient-centered telehealth
      outcome goals may allow meaningful generation of telehealth alerts. Reducing
      avoidable telehealth alerts could vastly improve the efficiency and
      sustainability of telehealth programs for HF management.

PMID- 24454577
TI  - The association between use of a clinical decision support tool and adherence to
      monitoring for medication-laboratory guidelines in the ambulatory setting.
AB  - BACKGROUND: Stage 2 Meaningful Use criteria require the use of clinical decision
      support systems (CDSS) on high priority health conditions to improve clinical
      quality measures. Although CDSS hold great promise, implementation has been
      fraught with challenges, evidence of their impact is mixed, and the optimal
      method of content delivery is unknown. OBJECTIVE: The authors investigated
      whether implementation of a simple clinical decision support (CDS) tool was
      associated with improved prescriber adherence to national medication-laboratory
      monitoring guidelines for safety (hepatic function, renal function,
      myalgias/rhabdomyolysis) and intermediate outcomes for antidiabetic (Hemoglobin
      A(1c); HbA(1c)) and antihyperlipidemic (low density lipoprotein; LDL) medications
      prescribed within a diabetes registry. METHODS: This was a retrospective
      observational study conducted in three phases of CDS implementation (2008-2009):
      pre-, transition-, and post-Prescriptions evaluated were ordered from an
      electronic health record within a multispecialty medical group. Adherence was
      evaluated within and without applying guideline-imposed time constraints.
      RESULTS: Forty-thousand prescriptions were ordered over three timeframes. For
      hepatic and renal function, the proportion of prescriptions for which labs were
      monitored at any time increased from 52% to 65% (p<0.001); those that met time
      guidelines, from 14% to 21% (p<0.001). Only 6% of required labs were drawn to
      monitor for myalgias/rhabdomyolysis, regardless of timeframe. Over 90% of safety
      labs were within normal limits. The proportion of labs monitored at any time for
      LDL increased from 56% to 64% (p<0.001); those that met time guidelines from 11%
      to 17% (p<0.001). The proportion of labs monitored at any time for HbA(1c)
      remained the same (72%); those that met time guidelines decreased from 45% to 41%
      (p<0.001). CONCLUSION: A simple CDS tool may be associated with improved
      adherence to guidelines. Efforts are needed to confirm findings and improve the
      timeliness of monitoring; investigations to optimize alerts should be ongoing.

PMID- 24454578
TI  - Information technology improves Emergency Department patient discharge
      instructions completeness and performance on a national quality measure: a quasi
      experimental study.
AB  - OBJECTIVE: To compare the completeness of Emergency Department (ED) discharge
      instructions before and after introduction of an electronic discharge
      instructions module by scoring compliance with the Centers for Medicare and
      Medicaid Services (CMS) Outpatient Measure 19 (OP-19). METHODS: We performed a
      quasi-experimental study examining the impact of an electronic discharge
      instructions module in an academic ED. Three hundred patients discharged home
      from the ED were randomly selected from two time intervals: 150 patients three
      months before and 150 patients three to five months after implementation of the
      new electronic module. The discharge instructions for each patient were reviewed,
      and compliance for each individual OP-19 element as well as overall OP-19
      compliance was scored per CMS specifications. Compliance rates as well as risk
      ratios (RR) and risk differences (RD) with 95% confidence intervals (CI)
      comparing the overall OP-19 scores and individual OP-19 element scores of the
      electronic and paper-based discharge instructions were calculated. RESULTS: The
      electronic discharge instructions had 97.3% (146/150) overall OP-19 compliance,
      while the paper-based discharge instructions had overall compliance of 46.7%
      (70/150). Electronic discharge instructions were twice as likely to achieve
      overall OP-19 compliance compared to the paper-based format (RR: 2.09, 95% CI:
      1.75 - 2.48). The largest improvement was in documentation of major procedures
      and tests performed: only 60% of the paper-based discharge instructions satisfied
      this criterion, compared to 100% of the electronic discharge instructions (RD:
      40.0%, 95% CI: 32.2% - 47.8%). There was a modest difference in medication
      documentation with 92.7% for paper-based and 100% for electronic formats (RD:
      7.3%, 95% CI: 3.2% - 11.5%). There were no statistically significant differences
      in documentation of patient care instructions and diagnosis between paper-based
      and electronic formats. CONCLUSION: With careful design, information technology
      can improve the completeness of ED patient discharge instructions and performance
      on the OP-19 quality measure.

PMID- 24454579
TI  - Automating case definitions using literature-based reasoning.
AB  - BACKGROUND: Establishing a Case Definition (CDef) is a first step in many
      epidemiological, clinical, surveillance, and research activities. The application
      of CDefs still relies on manual steps and this is a major source of inefficiency
      in surveillance and research. OBJECTIVE: Describe the need and propose an
      approach for automating the useful representation of CDefs for medical
      conditions. METHODS: We translated the existing Brighton Collaboration CDef for
      anaphylaxis by mostly relying on the identification of synonyms for the criteria
      of the CDef using the NLM MetaMap tool. We also generated a CDef for the same
      condition using all the related PubMed abstracts, processing them with a text
      mining tool, and further treating the synonyms with the above strategy. The co
      occurrence of the anaphylaxis and any other medical term within the same sentence
      of the abstracts supported the construction of a large semantic network. The
      'islands' algorithm reduced the network and revealed its densest region including
      the nodes that were used to represent the key criteria of the CDef. We evaluated
      the ability of the "translated" and the "generated" CDef to classify a set of
      6034 H1N1 reports for anaphylaxis using two similarity approaches and comparing
      them with our previous semi-automated classification approach. RESULTS: Overall
      classification performance across approaches to producing CDefs was similar, with
      the generated CDef and vector space model with cosine similarity having the
      highest accuracy (0.825 +/- 0.003) and the semi-automated approach and vector
      space model with cosine similarity having the highest recall (0.809 +/- 0.042).
      Precision was low for all approaches. CONCLUSION: The useful representation of
      CDefs is a complicated task but potentially offers substantial gains in
      efficiency to support safety and clinical surveillance.

PMID- 24454580
TI  - A pilot trial of a computerized renal template note to improve resident knowledge
      and documentation of kidney disease.
AB  - BACKGROUND: Kidney disease is under-documented in physician notes. The use of
      template-guided notes may improve physician recognition of kidney disease early
      in training. OBJECTIVE: The objective of this study was to determine whether a
      computerized inpatient renal template note with clinical decision support
      improves resident knowledge and documentation of kidney disease. METHODS: In this
      prospective study, first year medical residents were encouraged to use the renal
      template note for documentation over a one-month period. The renal template note
      included an option for classification of acute kidney injury (AKI) and chronic
      kidney disease (CKD) categories with a link to standard classifications. Pre- and
      post-knowledge of AKI and CKD categories was tested with a quiz and surveys of
      resident experience with the intervention were conducted. Appropriate AKI and/or
      CKD classification was determined in 100 renal template notes and 112 comparable
      historical internal medicine resident progress notes from approximately one year
      prior. RESULTS: 2,435 inpatient encounters amongst 15 residents who participated
      were documented using the renal template note. A significantly higher percent of
      residents correctly staged earlier stage CKD (CKD3) using the renal template note
      compared to historical notes (9/46 vs. 0/33, p<0.01). Documentation of AKI and
      more advanced CKD stages (CKD4 and 5) did not improve. Knowledge based on quiz
      scores increased modestly but was not significant. The renal template note was
      well received by residents and was perceived as helping improve knowledge and
      documentation of kidney disease. CONCLUSION: The renal template note
      significantly improved staging of earlier stage CKD (CKD3) with a modest but non
      significant improvement in resident knowledge. Given the importance of early
      recognition and treatment of CKD, future studies should focus on teaching early
      recognition using template notes with supplemental educational interventions.

PMID- 24454581
TI  - Clinical communication in diagnostic imaging studies: mixed-method study of pre-
      and post-implementation of a hospital information system.
AB  - OBJECTIVE: To examine how and why the quality of clinical communication between
      radiologists and referring physicians was changed in the inpatient imaging
      process after implementation of a hospital information system (HIS). METHODS: A
      mixed-method study of the chest X-ray (CXR) requests and reports, and their
      involved processes within a pre- and post-HIS implementation setting. RESULTS:
      Documentation of patient age, patient ward, and name and signature of requesting
      physician decreased significantly in post-HIS CXR requests (P<0.05). However,
      documentation of requested position and technique increased significantly
      (P<0.05). In post-HIS CXR reports, documentation of patient age, patient chart
      number, urgent/normal status of requisition, position and technique of CXR, name
      of referring physician, and date of request were increased significantly
      (P<0.05). However, documentation of discussion for important findings was
      decreased significantly (P<0.05). The mean number of words in the body text of
      post-HIS reports was increased significantly (18.65 vs. 16.3, P = 0.00).Our
      qualitative findings highlighted that involving nursing and radiology staff in
      the communication loop between physicians and radiologists after the
      implementation resulted in extra steps in the workflow and more workload for
      them. To cope with the new workload, they adopted different workarounds that
      could explain the results seen in the quantitative study. CONCLUSION: The HIS
      improved communication of administrative and identification information but did
      not improve communication of clinically relevant information. The reason was
      traced to the complications that the inappropriate implementation of the system
      brought to clinical workflow and communication loop.

PMID- 24454582
TI  - Conversion of a single-facility pediatric antimicrobial stewardship program to
      multi-facility application with computerized provider order entry and clinical
      decision support.
AB  - OBJECTIVE: Antimicrobial stewardship programs (ASPs) help meet quality and safety
      goals with regard to antimicrobial use. Prior to CPOE implementation, the ASP at
      our pediatric tertiary hospital developed a paper-based order set containing
      recommendations for optimization of dosing. In adapting our ASP for CPOE, we
      aimed to preserve consistency in our ASP recommendations and expand ASP expertise
      to other hospitals in our health system. METHODS: Nine hospitals in our health
      system adopted pediatric CPOE and share a common domain (Cerner Millenium). ASP
      clinicians developed sixty individual electronic order sets (vendor reference
      PowerPlans) to be used independently or as part of larger electronic order sets.
      Analysis of incidents reported during CPOE implementation and medication
      variances reports was used to determine the effectiveness of the ASP adaptation.
      RESULTS: 769 unique PowerPlans were used 15,889 times in the first 30 days after
      CPOE implementation. Of these, 43 were PowerPlans included in the ASP design and
      were used a total of 1149 times (7.2% of all orders). During CPOE implementation,
      437 incidents were documented, 1.1% of which were associated with ASP content or
      workflow. Additionally, analysis of medication variance following CPOE
      implementation showed that ASP errors accounted for 2.9% of total medication
      variances. DISCUSSION: ASP content and workflow accounted for proportionally
      fewer incidents than expected as compared to equally complex and frequently used
      CPOE content. CONCLUSION: Well-defined ASP recommendations and modular design
      strengthened successful CPOE implementation, as well as the adoption of
      specialized pediatric ASP expertise with other facilities.

PMID- 24454583
TI  - A retrospective analysis of interruptive versus non-interruptive clinical
      decision support for identification of patients needing contact isolation.
AB  - BACKGROUND: In determining whether clinical decision support (CDS) should be
      interruptive or non-interruptive, CDS designers need more guidance to balance the
      potential for interruptive CDS to overburden clinicians and the potential for non
      interruptive CDS to be overlooked by clinicians. OBJECTIVE: (1)To compare
      performance achieved by clinicians using interruptive CDS versus using similar,
      non-interruptive CDS. (2)To compare performance achieved using non-interruptive
      CDS among clinicians exposed to interruptive CDS versus clinicians not exposed to
      interruptive CDS. METHODS: We studied 42 emergency medicine physicians working in
      a large hospital where an interruptive CDS to help identify patients requiring
      contact isolation was replaced by a similar, but non-interruptive CDS. The first
      primary outcome was the change in sensitivity in identifying these patients
      associated with the conversion from an interruptive to a non-interruptive CDS.
      The second primary outcome was the difference in sensitivities yielded by the non
      interruptive CDS when used by providers who had and who had not been exposed to
      the interruptive CDS. The reference standard was an epidemiologist-designed,
      structured, objective assessment. RESULTS: In identifying patients needing
      contact isolation, the interruptive CDS-physician dyad had sensitivity of 24%
      (95% CI: 17%-32%), versus sensitivity of 14% (95% CI: 9%-21%) for the non
      interruptive CDS-physician dyad (p = 0.04). Users of the non-interruptive CDS
      with prior exposure to the interruptive CDS were more sensitive than those
      without exposure (14% [95% CI: 9%-21%] versus 7% [95% CI: 3%-13%], p = 0.05).
      LIMITATIONS: As with all observational studies, we cannot confirm that our
      analysis controlled for every important difference between time periods and
      physician groups. CONCLUSIONS: Interruptive CDS affected clinicians more than non
      interruptive CDS. Designers of CDS might explicitly weigh the benefits of
      interruptive CDS versus its associated increased clinician burden. Further
      research should study longer term effects of clinician exposure to interruptive
      CDS, including whether it may improve clinician performance when using a similar,
      subsequent non-interruptive CDS.

PMID- 24454584
TI  - Audit and feedback of antibiotic use: utilising electronic prescription data.
AB  - BACKGROUND: There is now little doubt that improving antimicrobial use is
      necessary for the containment of resistance. OBJECTIVE: To determine whether
      providing individualised feedback to doctors about their recent compliance with
      the hospital's antibiotic policy improves compliance with the policy. METHODS:
      This study was conducted at a teaching hospital in Sydney, Australia.
      Computerised alerts integrated into the electronic prescribing system (ePS)
      inform prescribers of the local antibiotic policy. We utilised prescribing data
      extracted from the ePS for 'audit and feedback'. Thirty-six prescribers were sent
      feedback letters via email. We also interviewed doctors who had received letters
      to explore their views of the feedback and the policy in general. RESULTS: There
      was no significant change in compliance with the policy following implementation
      of the feedback intervention (0% compliant vs 11.9%; p = 0.07). Several problems
      with the policy and the approval process were identified by researchers during
      auditing and by prescribers during interviews. Some problems identified made it
      difficult to accurately assess compliance and for doctors to comply with the
      policy. CONCLUSION: Our intervention did not result in improved compliance with
      the antibiotic policy but revealed practical problems with the policy and
      approval process that had not been identified prior to the trial. Greater support
      for the policy by senior doctors and the assignment of more clearly defined roles
      and responsibilities associated with antibiotic use and approval may result in
      improved compliance. Harnessing the full potential of technology would streamline
      the antimicrobial approval process and allow more efficient and reliable
      monitoring of antibiotic use and compliance. Many of the problems we identified
      are generic issues of importance to all organisations seeking to integrate
      antimicrobial stewardship into ePS.

PMID- 24454585
TI  - Lessons learned from developing a drug evidence base to support
      pharmacovigilance.
AB  - OBJECTIVE: This work identified challenges associated with extraction and
      representation of medication-related information from publicly available
      electronic sources. METHODS: We gained direct observational experience through
      creating and evaluating the Drug Evidence Base (DEB), a repository of drug
      indications and adverse effects (ADEs), and supplemented this through literature
      review. We extracted DEB content from the National Drug File Reference
      Terminology, from aggregated MEDLINE co-occurrence data, and from the National
      Library of Medicine's DailyMed. To understand better the similarities,
      differences and problems with the content of DEB and the SIDER Side Effect
      Resource, and Vanderbilt's MEDI Indication Resource, we carried out statistical
      evaluations and human expert reviews. RESULTS: While DEB, SIDER, and MEDI often
      agreed on medication indications and side effects, cross-system shortcomings
      limit their current utility. The drug information resources we evaluated
      frequently employed multiple, disparate vaguely related UMLS concepts to
      represent a single specific clinical drug indication or adverse effect. Thus,
      evaluations comparing drug-indication and drug-ADE coverage for such resources
      will encounter substantial numbers of false negative and false positive matches.
      Furthermore, our review found that many indication and ADE relationships are too
      complex - logically and temporally - to represent within existing systems.
      CONCLUSION: To enhance applicability and utility, future drug information systems
      deriving indications and ADEs from public resources must represent clinical
      concepts uniformly and as precisely as possible. Future systems must also better
      represent the inherent complexity of indications and ADEs.

PMID- 24454586
TI  - Transforming user needs into functional requirements for an antibiotic clinical
      decision support system: explicating content analysis for system design.
AB  - BACKGROUND: Many informatics studies use content analysis to generate functional
      requirements for system development. Explication of this translational process
      from qualitative data to functional requirements can strengthen the understanding
      and scientific rigor when applying content analysis in informatics studies.
      OBJECTIVE: To describe a user-centered approach transforming emergent themes
      derived from focus group data into functional requirements for informatics
      solutions and to illustrate these methods to the development of an antibiotic
      clinical decision support system (CDS). METHODS: THE APPROACH CONSISTED OF FIVE
      STEPS: 1) identify unmet therapeutic planning information needs via Focus Group
      Study-I, 2) develop a coding framework of therapeutic planning themes to refine
      the domain scope to antibiotic therapeutic planning, 3) identify functional
      requirements of an antibiotic CDS system via Focus Group Study-II, 4) discover
      informatics solutions and functional requirements from coded data, and 5)
      determine the types of information needed to support the antibiotic CDS system
      and link with the identified informatics solutions and functional requirements.
      RESULTS: The coding framework for Focus Group Study-I revealed unmet therapeutic
      planning needs. Twelve subthemes emerged and were clustered into four themes;
      analysis indicated a need for an antibiotic CDS intervention. Focus Group Study
      II included five types of information needs. Comments from the Barrier/Challenge
      to information access and Function/Feature themes produced three informatics
      solutions and 13 functional requirements of an antibiotic CDS system. Comments
      from the Patient, Institution, and Domain themes generated required data elements
      for each informatics solution. CONCLUSION: This study presents one example
      explicating content analysis of focus group data and the analysis process to
      functional requirements from narrative data. Illustration of this 5-step method
      was used to develop an antibiotic CDS system, resolving unmet antibiotic
      prescribing needs. As a reusable approach, these techniques can be refined and
      applied to resolve unmet information needs with informatics interventions in
      additional domains.

PMID- 24454587
TI  - Risk factors for infection following total joint arthroplasty in rheumatoid
      arthritis.
AB  - OBJECTIVES: Determine risk factors for infection following hip or knee total
      joint arthroplasty in patients with rheumatoid arthritis. METHODS: All rheumatoid
      arthritis patients with a hip or knee arthroplasty between years 2000 and 2010
      were identified from population-based administrative data from the Calgary Zone
      of Alberta Health Services. Clinical data from patient charts during the hospital
      admission and during a one year follow-up period were extracted to identify
      incident infections. RESULTS: We identified 381 eligible procedures performed in
      259 patients (72.2% female, mean age 63.3 years, mean body mass index 27.6
      kg/m2). Patient comorbidities were hypertension (43.2%), diabetes (10.4%),
      coronary artery disease (13.9%), smoking (10.8%) and obesity (32%). Few
      infectious complications occurred: surgical site infections occurred within the
      first year after 5 procedures (2 joint space infections, 3 deep incisional
      infections). Infections of non-surgical sites (urinary tract, skin or
      respiratory, n=4) complicated the hospital admission. The odds ratio for any post
      arthroplasty infection was increased in patients using prednisone doses exceeding
      15 mg/day (OR 21.0, 95%CI 3.5-127.2, p=<0.001), underweight patients (OR 6.0,
      95%CI 1.2-30.9, p=0.033) and those with known coronary artery disease (OR 5.1,
      95%CI 1.3-19.8, p=0.017). Types of disease-modifying therapy, age, sex, and other
      comorbidities were not associated with an increased risk for infection.
      CONCLUSION: Steroid doses over 15 mg/day, being underweight and having coronary
      artery disease were associated with significant increases in the risk of post
      arthroplasty infection in rheumatoid arthritis. Maximal tapering of prednisone
      and comorbidity risk reduction must be addressed in the peri-operative management
      strategy.

PMID- 24454588
TI  - Eight New Monoterpene Acylglucosides from Sibiraea angustata.
AB  - Chemical investigation of the aqueous extract from the aerial part of Sibiraea
      angustata, has led to the isolation of eight new monoterpene acylglucosides named
      sibiraglycoside A-H(1-8), together with two known monoterpenes, Sibiraic acid (9)
      and Sibiskoside (10). Their structures were elucidated by means of extensive
      spectroscopic data analysis (including 1D and 2D NMR, HRESIMS experiments), as
      well as compared with the literature data. The relative configuration was
      established by NOE studies. In the in vitro bioassay, all the compounds showed
      moderate hypolipemic effects, among them, compounds 7 and 9, showed distinctive
      activity on lowering lipid.

PMID- 24454589
TI  - Patient Reported Outcome Measure (PROM) of Quality of Life After Prostatectomy -
      Results from a 5-Year Study.
AB  - Prostate cancer is the most common cancer among men in Sweden, and treatment is
      negatively affecting the patients' quality of life. Even so, long term
      experiences are sparse and implications for nursing practice are little known.
      The aim of this study was to determine areas of functioning and factors impacting
      quality of life, QOL, during and five years after radical prostatectomy (RP)
      using a quality of life questionnaire and a specific module for prostate cancer.
      A longitudinal study was performed with consecutively included Swedish men from
      baseline and after RP treatment (n=222) from 2003 to 2011 to obtain their
      opinions on quality of life. Data was gathered through a mail out - mail in
      procedure at baseline, 3 months, 1-3 and 5 years after treatment with a response
      rate of 94.14% - 75.2%. One reminder was sent on each occasion. Identified areas
      with increased functioning after five years were emotional and social
      functioning. QOL ratings did not change over the years. Sexual activity and
      functioning decreased and hormonal treatment-related symptoms increased. Impact
      on QOL was found regarding emotional and social functioning, nausea/vomiting,
      pain and hormone-related symptoms. Increasing age, living with a partner and
      educational level had no significant impact on QOL. Implications for nursing are
      to initially focus on physical problems and at times for follow-up visits pay
      attention also to emotional and social aspects of life. To be able to make a
      difference in the patient's life, nurses need to bridge the gap between in
      hospital treatment and everyday life outside hospital. 

PMID- 24454590
TI  - Older Adults with HIV/AIDS in Rural China.
AB  - Although the number of older people living with HIV/AIDS (PLWHA) has increased
      substantially, few studies have focused on older PLWHA in developing countries.
      Based on a sample of 866 rural PLWHA in Henan, Anhui and Yunnan provinces in
      China, this study compares the characteristics of PLWHA aged 50 or older (n=185)
      with younger PLWHA (n=681). Most of the older PLWHA were female (n=112),
      illiterate, married and at the clinical stage of HIV. Over 90% of older people
      with HIV/AIDS lived in Henan and Anhui provinces. The severe epidemic in Henan
      and Anhui provinces was caused by commercial blood and plasma donation. Older
      PLWHA were less educated, received less social support and were more likely to
      live alone than younger PLWHA. The results underline the importance of developing
      programs and policy initiatives targeted at older people infected with HIV/AIDS.
      The policy and program recommendations include using a gender sensitive strategy,
      designing specific AIDS education and prevention programs suitable for low
      literacy older adults and social support interventions for older PLWHA. 

PMID- 24454591
TI  - A neonatal oral Mycobacterium tuberculosis-SIV prime / intramuscular MVA-SIV
      boost combination vaccine induces both SIV and Mtb-specific immune responses in
      infant macaques.
AB  - Mother-to-child-transmission of HIV by breast-feeding remains a major obstacle in
      the eradication of HIV infection. Compared to adults, HIV-infected infants have
      more rapid disease and show higher susceptibility to co-infections like
      tuberculosis (TB). Although the Bacille Calmette-Guerin vaccine can be
      administered at birth to protect against TB, BCG can disseminate in HIV-infected
      infants and increase mortality. Thus, a pediatric combination vaccine to stop
      both HIV and TB infection in infants is urgently needed. Towards the goal of
      developing a pediatric combination HIV-TB vaccine to prevent both oral HIV
      acquisition by breast-feeding and TB infection, we tested and optimized an
      immunization regimen using a novel live attenuated Mycobacterium tuberculosis
      vaccine engineered to express simian immunodeficiency (SIV) antigens followed by
      heterologous MVA-SIV boosting in the infant macaque model. A single oral dose of
      the attenuated Mtb-SIV vaccine strain mc26435 during the first week of life was
      sufficient to induce persistent TB-specific immune responses. SIV-specific
      immunity was induced at low but comparable magnitudes after oral or intradermal
      priming, and was enhanced following MVA-SIV boosts. T cell responses were most
      pronounced in intestinal tissues and oral lymph nodes. Importantly, in addition
      to plasma SIV-specific IgG and IgA antibodies, infant macaques developed mucosal
      SIV-specific IgA in saliva and intestinal IgA and IgG. While future SIV and Mtb
      challenge studies will be needed to determine the protective efficacy of the Mtb
      SIV / MVA-SIV vaccine, infants at high risk for oral HIV acquisition by breast
      feeding and TB infection could profoundly benefit from an effective combination
      vaccine.

PMID- 24454592
TI  - PEComa of soft tissues can mimic lymph node relapse in patients with history of
      testicular seminoma.
AB  - Perivascular Epithelioid Cell tumour (PEComa) is rare. We describe a 39-year-old
      man who underwent a left radical orchidectomy and adjuvant radiation therapy for
      a stage IA classical testicular seminoma. He was diagnosed with a mass lateral to
      the right common iliac artery that was considered suspicious for late lymph node
      relapse after 3 years of follow-up. Due to the unusual location of the mass and
      the equivocal findings of percutaneous biopsy, a laparoscopic pelvic
      lymphadenectomy was performed. Final pathology revealed PEComa of soft tissue.
      The patient is disease-free after 38 months of follow-up without adjuvant
      treatment. The presence of rare soft-tissue neoplasm should be considered in
      differential diagnosis of retroperitoneal masses during follow-up of germ cell
      tumours. Suspicious isolated recurrences of these neoplasms in unusual locations
      can require surgical excision to confirm diagnosis and avoid inappropriate
      treatment. 

PMID- 24454593
TI  - Cost analysis of fixed-dose combination of dutasteride and tamsulosin compared
      with concomitant dutasteride and tamsulosin monotherapy in patients with benign
      prostatic hyperplasia in Canada.
AB  - INTRODUCTION: We estimate the lifetime cost of treatment for moderate/severe
      symptoms associated with benign prostatic hyperplasia (BPH) in a cohort of
      Canadian men aged 50 to 59, and we evaluate the costs of 2 daily bioequivalent
      treatment options: fixed-dose combination (FDC) of dutasteride (0.5 mg) and
      tamsulosin (0.4 mg), or concomitant administration of dutasteride (0.5 mg) and
      tamsulosin (0.4 mg) monotherapies. METHODS: The expected lifetime costs were
      estimated by modelling the incidence of acute urinary retention (AUR), BPH
      related surgery and clinical progression over a patient's lifetime (up to 25
      years). A model was developed to simulate clinical events over time, based on a
      discrete Markov process with 6 mutually exclusive health states and annual cycle
      length. RESULTS: The estimated lifetime budget cost for the cohort of 374 110 men
      aged 50 to 59 in Canada is between $6.35 billion and $7.60 billion, equivalent to
      between $16 979 and $20 315 per patient with moderate/severe symptoms associated
      with BPH. Costs are lower for FDC treatment, with the net difference in lifetime
      budget impact between the 2 treatment regimens at $1.25 billion. In this
      analysis, the true costs of BPH in Canada are underestimated for 2 main reasons:
      (1) to make the analysis tractable, it is restricted to a cohort aged 50 to 59,
      whereas BPH can affect all men; and (2) a closed cohort approach does not include
      the costs of new (incident) cases. CONCLUSION: Canadian clinical guidelines
      recommend the use of the combination of tamsulosin and dutasteride for men with
      moderate/severe symptoms associated with BPH and enlarged prostate volume. This
      analysis, using a representational patient group, suggests that the FDC is a more
      cost-effective treatment option for BPH.

PMID- 24454594
TI  - Peristeen anal irrigation as a substitute for the MACE procedure in children who
      are in need of reconstructive bladder surgery.
AB  - INTRODUCTION: We evaluate the efficacy of the Peristeen (Coloplast A/S, Kokkedal,
      Denmark) transanal irrigation (TAI) system, as a stool cleansing mechanism, to
      gain stool continence in children who need reconstructive bladder surgery and
      have fecal incontinence. METHODS: We prospectively evaluated children with
      neuropathic bladder and bowel dysfunction who were intended for reconstructive
      bladder surgery and the Malone antegrade continence enema (MACE) procedure. All
      patients were started on the Peristeen TAI system at least 3 months before
      surgery to assess their response. Each patient's bowel function, frequency of
      using the system, satisfaction (and that of their parents) and diaper
      independency were evaluated before and after reconstructive surgery. RESULTS: We
      included 18 patients (11 female, 7 male) who were evaluated from April 2006 to
      the present. The mean age of the group was 7.6 years (range: 4-15). Fifteen
      patients (83.3%) showed complete dryness from stools. Of the 15 patients, 8
      (53.3%) were able to be diaper-free, while 6 continued wearing diapers due to
      fear of soiling and 1 due to urinary incontinence. The patients underwent
      reconstructive bladder surgery and continued to use the Peristeen TAI system with
      the same results postoperatively. The main limitation of this study is the small
      number of patients included, although this is a very specific patient group.
      CONCLUSION: Our initial results suggest that the Peristeen TAI system is a
      successful conservative substitute for the MACE procedure in children who require
      reconstructive bladder surgery.

PMID- 24454595
TI  - Outcome of urethral strictures treated by endoscopic urethrotomy and
      urethroplasty.
AB  - INTRODUCTION: We analyze the outcomes of patients with urethral stricture who
      underwent surgical treatment within the past 5 years. METHODS: This is a
      retrospective study of male patients who underwent surgery for urethral stricture
      at our service from January 2008 to June 2012. We analyzed the comorbidities,
      type, length and location of the stricture and the surgical treatment outcome
      after endoscopic urethrotomy, urethroplasty or both. RESULTS: In total, 45
      patients with a mean age of 53.7 +/- 16.7 years underwent surgical treatment for
      urethral stricture. Six months after surgery, 46.7% of the patients had a maximum
      urinary flow greater than 15 mL/s, whereas 87.3% of the patients exhibited no
      stricture by urethrography after the treatment. The success rate in the patients
      undergoing urethrotomy was 47.8% versus 86.4% in those undergoing urethroplasty
      (p = 0.01). Twenty percent of the patients in whom the initial urethrotomy had
      failed subsequently underwent urethroplasty, thereby increasing the treatment
      success. CONCLUSION: In most cases, the treatment of choice for urethral
      stricture should be urethroplasty. Previous treatment with urethrotomy does not
      appear to produce adverse effects that affect the outcome of a urethroplasty if
      urethrotomy failed, so urethrotomy may be indicated in patients with short
      strictures or in patients at high surgical risk.

PMID- 24454596
TI  - Patient-reported satisfaction and cosmesis outcomes following laparoscopic
      adrenalectomy: Laparoendoscopic single-site adrenalectomy vs. conventional
      laparoscopic adrenalectomy.
AB  - INTRODUCTION: We evaluate patient-reported satisfaction and cosmesis of
      laparoendoscopic single-site adrenalectomy (LESS-A) in comparison with that of
      conventional laparoscopic adrenalectomy (CLA). METHODS: A total of 19 and 104
      patients who respectively underwent LESS-A and CLA between May 1996 and June 2011
      were included in the study. Questionnaires inquiring about scar pain (0: not
      painful, 10: very painful), satisfaction (0: not satisfied, 10: very satisfied)
      and cosmesis (0: very unsightly, 10: very beautiful) on the basis of a visual
      analogue scale were sent to patients postoperatively. RESULTS: The respondents
      consisted of 11 and 54 patients who underwent LESS-A and CLA, respectively. There
      was no significant inter-group difference in age, sex, affected side or body mass
      index. No significant differences were observed in operative time or estimated
      blood loss. There were also no significant differences in pain (0.67 vs. 0.57, p
      = 0.393), satisfaction (8.92 vs. 8.46, p = 0.453), or cosmesis score (8.58 vs.
      8.00, p = 0.487) between the LESS-A and CLA groups overall. In female patients,
      the satisfaction score was significantly higher in the LESS-A group than in the
      CLA group (10.0 vs. 8.72, p = 0.049). In young patients (<50 years old), the
      satisfaction score was also significantly higher in the LESS-A group than in the
      CLA group (9.17 vs. 6.38, p = 0.036). CONCLUSIONS: Young patients and female
      patients who had received LESS-A adrenal surgery were more satisfied with the
      scar outcomes than were the young patients and female patients who had received
      CLA. We suggest that this patient subset most values the cosmetic benefits of
      LESS-A.

PMID- 24454597
TI  - The relationship between bladder wall thickness and lower urinary tract symptoms:
      Does bladder wall thickness change after alpha-blocker therapy with alfuzosin?
AB  - INTRODUCTION: We evaluate the association between lower urinary tract symptoms
      (LUTS) and bladder wall thickness (BWT) and investigate whether alfuzosin might
      improve BWT. METHODS: We retrospectively reviewed the data of 164 patients with
      LUTS. Patients were divided into 2 groups according to BWT (Group 1: BWT <=5 mm,
      n = 69; Group 2: BWT >5 mm, n = 95). Age, international prostate symptom score
      (IPSS), maximum and average urinary flow rates (Qmax and Qave), quality of life
      (QoL), postvoid residual (PVR) urine volume, prostate volume and prostate
      specific antigen (PSA) were compared between the 2 groups. In total, 102 patients
      underwent transurethral resection of the prostate (TURP) and 62 patients were
      treated with alfuzosin. We compared BWT, Qmax, Qave, IPSS, QoL, PVR and PSA
      before and at the sixth month of alfuzosin therapy. A p value of <0.05 was
      considered statistically significant. RESULTS: The mean BWT of Group 1 was 3.72
      +/- 0.56 mm and Group 2 was 6.43 +/- 1.13 mm. There was a significant difference
      between the 2 groups in terms of mean Qmax and PVR. There was no statistical
      difference between the groups in terms of Qave, IPSS, QoL, prostate volume and
      PSA. There was significant difference between BWT before (6.8 +/- 2.1) and after
      (4.6 +/- 1.3) treatment with alfuzosin in 62 patients (p = 0.02). There was a
      significant difference between pre- and post-treatment values of mean Qmax, Qave,
      IPSS, QoL score, and PVR with alfuzosin. CONCLUSION: BWT is a non-invasive and
      effective test to evaluate patients with lower urinary tract obstruction and may
      be used for showing the effectiveness of alpha-blocker therapy in patients with
      LUTS.

PMID- 24454598
TI  - Comparison of outpatient versus inpatient transurethral prostate resection for
      benign prostatic hyperplasia: Comparative, prospective bi-centre study.
AB  - INTRODUCTION: We compare the symptomatic relief with urodynamic parameter change
      and operative safety of the outpatient transurethral resection in saline (TURIS
      V) technique with inpatient transurethral resection of the prostate (TURP) for
      the management of benign prostatic hyperplasia (BPH). METHODS: This prospective
      cohort comparison study enrolled patients who needed BPH surgery. Between January
      2010 and June 2011, outpatient TURIS-V was performed at 1 centre and the results
      of the treatment were compared with inpatient TURP performed at a separate
      hospital. Preoperative characteristics, including prostate volume, were similar
      in both groups. Perioperative data and any treatment complications were recorded.
      The analysis compared postoperative outcomes, including a 6-month postoperative
      International Prostate Symptom Score (IPSS), a quality of life (QoL) evaluation
      and a record of any changes in uroflowmetry findings, between the 2 groups.
      RESULTS: In the TURIS-V patient group, 75 patients agreed to be in the study. Of
      these, 69 ultimately complete the study. In the TURP group, 76 patients agreed
      and 71 of these completed the study. Both study groups were well-matched for age,
      IPSS, QoL and uroflowmetry findings. The TURIS-V group experienced both shorter
      operation times (54.6 vs. 74.8 minutes) and shorter catheterization times (2.2
      vs. 4.2 days) when compared to the TURP group. There were comparable improvements
      in the 6-month postoperative IPSS, QoL, and uroflowmetry findings between the 2
      groups. There were also equally low incidence rates of procedural complications.
      CONCLUSIONS: Both TURIS-V and TURP relieve lower urinary tract symptoms in a
      similar way, with great efficacy and safety. Overall, TURIS-V had shorter
      operative and catheterization times compared to TURP. Notwithstanding the paper's
      limitations (non- randomized cohort comparison with possible selection or surgeon
      bias and small heterogeneous sample size), TURIS-V can be performed safely even
      in an outpatient setting.

PMID- 24454599
TI  - [Not Available].

PMID- 24454600
TI  - Ganglioneuroma with leiomyomatosis of the urinary bladder: A rare tumour causing
      frequent micturition and dysuria.
AB  - We present the case of a 34-year-old female, complaining of frequent micturition
      and progressive dysuria. By cystoscopy and computerized tomography, we found that
      she had multiple sub-mucosal protuberant lesions in the entire bladder. After
      surgical excision, she has thus far showed no further signs of the disease. The
      postoperative histopathologic examination revealed a ganglioneuroma and
      leiomyomatosis. Urinary bladder paraganglioma is an unusual tumour; when it is
      combined with leiomyomatosis, it is extremely rare. We describe the main clinical
      presentation, diagnostic procedures, and pathologic features. We also review the
      English literature. 

PMID- 24454601
TI  - Vesicouterine fistula presenting with urinary incontinence 30 years after primary
      Cesarean: Case report and review of the literature.
AB  - A vesicouterine fistula is an abnormal communication between the bladder and the
      uterus. The most common cause is lower segment Cesarean section. Conservative
      treatment may be applied in some cases, but surgery is the definitive treatment.
      We present a 55-year-old woman with vesicouterine fistula after primary Cesarean
      section; she presented with urinary incontinence 30 years later. Methylene blue
      dye test was performed and drainage of urine dyed with methylene blue through the
      uterine cervix was observed. Diagnosis was confirmed with magnetic resonance
      imaging. Total abdominal hysterectomy and bilateral oophorectomy was performed
      and the bladder wall was sutured in a double layer with 2/0 polyglycolic suture.
      No complications developed and the patient did not suffer from any urinary
      incontinence afterwards. Vesicouterine fistula should be suspected in cases
      presenting with urinary incontinence even years after Cesarean section;
      diagnostic tests and, if necessary, appropriate surgery should be performed. 

PMID- 24454602
TI  - Penile fracture with bilateral corporeal rupture without urethral involvement.
AB  - Concomitant urethral injury is rare in penile fracture. We report the case of a
      34-year-old male who presented to the emergency department 12 hours after a blunt
      self-injury of the penis. Physical examination revealed a swollen, ecchymotic,
      and deviated circumcised penis without blood at the meatus. The fracture line
      extending along the bilateral corpora without urethral involvement was seen
      intraoperatively. The fracture side was repaired primarily. The patient healed
      and recovered without complication. To our knowledge, this is the second reported
      case of bilateral corporeal rupture without urethral involvement. 

PMID- 24454603
TI  - Malignant melanoma of the bladder: A case report.
AB  - Primary malignant melanoma of the bladder is very rare. Rather than being a
      primary lesion, malignant melanomas of the bladder are more commonly metastatic
      lesions. The histopathological appearance largely does not differ from that of
      melanoma at other body sites. It is often difficult to discriminate whether a
      bladder melanoma is primary or metastatic. Therefore, a careful review of
      histological features and performing necessary immunohistochemical staining
      procedures for S-100 protein and HMB-45 are very important in achieving a correct
      diagnosis. We report a case of hypomelanotic malignant melanoma of the bladder.
      Despite the variety of therapies available for primary melanomas of the bladder,
      the prognosis is still poor. 

PMID- 24454604
TI  - Penile necrosis requiring penectomy complicating recto-urethral fistula post
      prostate cancer external beam radiation and brachytherapy.
AB  - Radiation therapy is a well-recognized treatment for unfavourable risk localized
      prostate cancer. Radiation induced recto-urethral fistulae are known rare
      complications particularly from brachytherapy. We report a case of a recto
      urethral fistula 7 years post-external beam radiation and I-125 brachytherapy,
      which was complicated by a severe polymicrobial soft tissue infection. This
      infection required penectomy and pelvic exenteration with diverting colostomy,
      Indiana pouch urinary diversion and gracilis myo-cutaneuos flap closure of the
      perineum. 

PMID- 24454605
TI  - Unpublished abstracts can be invaluable.

PMID- 24454607
TI  - Prospective comparison of the impact of robotic-assisted laparoscopic radical
      prostatectomy versus open radical prostatectomy on health-related quality of life
      and decision regret.
AB  - INTRODUCTION: There is no conclusive evidence that the robotic-assisted
      laparoscopic radical prostatectomy (RARP) is superior to conventional open
      radical prostatectomy (ORP) when it comes to recovery of urinary and sexual
      function, and that the former surgical option results in less decision regret.
      METHODS: Patients scheduled for both surgical procedures were surveyed prior to
      surgery, and then again at 6 and 12 months following treatment using the sexual
      and urinary modules of the Expanded Prostate Cancer Index Composite (EPIC)
      measure. Decision regret was measured at 12 months. Propensity score regression
      adjustment was used to account for differences between treatment groups by
      summarizing all covariate information into a single probability and to simulate
      randomization. RESULTS: At 12 months, urinary summary scores approached baseline
      levels, while urinary bother scores had returned to baseline. Sexual summary and
      bother mean scores decreased by about half of what they were at baseline for both
      treatment groups at 6 and 12 months. No significant differences in the groups'
      sexual summary and bother domains were identified at either 6 or 12 months. Both
      groups' scores for decision regret were low. Moderate correlations (r(2) range 
      0.333 to -0.368) were between current levels of urinary and sexual function and
      decision regret at 12 months. CONCLUSION: The results of our study found no
      significant difference in health-related quality of life outcomes based on
      surgical procedure at 12 months. Moreover, patients in both groups reported low
      levels of decision regret at 12 months. Further multi-site prospective studies
      are required to address this study's limitations.

PMID- 24454606
TI  - Botulinum neurotoxin-A treatment of lower urinary tract symptoms in multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is the most common neuroinflammatory disease of the
      central nervous system and a leading cause of disability in young adults.
      Symptoms related to vesicourethral dysfunction are very prevalent, but not
      specific to underlying urodynamic abnormalities. Detrusor overactivity and
      detrusor external sphincter dysynergia are the most frequent findings and are
      usually linked. Botulinum neurotoxin-A injection represents a significant advance
      in the management of voiding dysfunction among MS patients failing first-line
      therapy. It significantly improves patients' urodynamic parameters and quality of
      life, with efficacy sustained by repeated injections and minimal risk of adverse
      events. 

PMID- 24454608
TI  - Usefulness of adjunctive alpha1-adrenergic antagonists after single
      extracorporeal shock wave lithotripsy session in ureteral stone expulsion.
AB  - INTRODUCTION: We evaluate the efficiency of alpha-adrenergic antagonists on stone
      clearance after extracorporeal shock wave lithotripsy (ESWL) in patients with
      lower ureteral stones. METHODS: A total of 356 patients with solitary lower
      ureteral stones who underwent single ESWL sessions were divided into 2 groups.
      Group 1 received our standard medical therapy, and Group 2 was treated with 0.4
      mg/day tamsulosin for a maximum of 2 weeks. All patients were re-evaluated with
      plain film radiography and ultrasound each week during the treatment period. A
      computed tomography scan was systematically performed 3 months after ESWL.
      RESULTS: In total, 82 of the 170 patients in Group 1 (48.2%) and 144 of the 186
      patients in Group 2 (77.4%) (p = 0.002) were stone-free. Among the patients with
      stones 10 to 15 mm in diameter, the stone-free rate was 38.4% in Group 1 and
      77.1% in Group 2 (p = 0.003). Average stone expulsion time was 10.6 days and 8.4
      days in Groups 1 and 2, respectively. Ureteral colic occurred in 40 patients
      (23.5%) in Group 1, but only in 10 patients (5.3%) in Group 2 (p = 0.043). The
      only side effect of tamsulosin was slight dizziness in 5 of the 186 patients in
      Group 2 (2.6%). CONCLUSION: Adjunctive therapy with alpha1-adrenergic antagonists
      after ESWL is more efficient than, and equally as safe as, lithotripsy alone to
      manage patients with lower ureteral stones. The adding of alpha-blockers is more
      reliable and helpful for stones with a large dimension, and can also decrease
      stone elimination time and episodes of ureteral colic.

PMID- 24454609
TI  - All-aqueous multiphase microfluidics.
AB  - Immiscible aqueous phases, formed by dissolving incompatible solutes in water,
      have been used in green chemical synthesis, molecular extraction and mimicking of
      cellular cytoplasm. Recently, a microfluidic approach has been introduced to
      generate all-aqueous emulsions and jets based on these immiscible aqueous phases;
      due to their biocompatibility, these all-aqueous structures have shown great
      promises as templates for fabricating biomaterials. The physico-chemical nature
      of interfaces between two immiscible aqueous phases leads to unique interfacial
      properties, such as an ultra-low interfacial tension. Strategies to manipulate
      components and direct their assembly at these interfaces needs to be explored. In
      this paper, we review progress on the topic over the past few years, with a focus
      on the fabrication and stabilization of all-aqueous structures in a multiphase
      microfluidic platform. We also discuss future efforts needed from the
      perspectives of fluidic physics, materials engineering, and biology for
      fulfilling potential applications ranging from materials fabrication to
      biomedical engineering. 

PMID- 24454610
TI  - Life under flow: A novel microfluidic device for the assessment of anti-biofilm
      technologies.
AB  - In the current study, we have developed and fabricated a novel lab-on-a-chip
      device for the investigation of biofilm responses, such as attachment kinetics
      and initial biofilm formation, to different hydrodynamic conditions. The
      microfluidic flow channels are designed using computational fluid dynamic
      simulations so as to have a pre-defined, homogeneous wall shear stress in the
      channels, ranging from 0.03 to 4.30 Pa, which are relevant to in-service
      conditions on a ship hull, as well as other man-made marine platforms. Temporal
      variations of biofilm formation in the microfluidic device were assessed using
      time-lapse microscopy, nucleic acid staining, and confocal laser scanning
      microscopy (CLSM). Differences in attachment kinetics were observed with
      increasing shear stress, i.e., with increasing shear stress there appeared to be
      a delay in bacterial attachment, i.e., at 55, 120, 150, and 155 min for 0.03,
      0.60, 2.15, and 4.30 Pa, respectively. CLSM confirmed marked variations in colony
      architecture, i.e.,: (i) lower shear stresses resulted in biofilms with
      distinctive morphologies mainly characterised by mushroom-like structures,
      interstitial channels, and internal voids, and (ii) for the higher shear stresses
      compact clusters with large interspaces between them were formed. The key
      advantage of the developed microfluidic device is the combination of three
      architectural features in one device, i.e., an open-system design, channel
      replication, and multiple fully developed shear stresses. 

PMID- 24454612
TI  - Tactile spatial acuity in childhood: effects of age and fingertip size.
AB  - Tactile acuity is known to decline with age in adults, possibly as the result of
      receptor loss, but less is understood about how tactile acuity changes during
      childhood. Previous research from our laboratory has shown that fingertip size
      influences tactile spatial acuity in young adults: those with larger fingers tend
      to have poorer acuity, possibly because mechanoreceptors are more sparsely
      distributed in larger fingers. We hypothesized that a similar relationship would
      hold among children. If so, children's tactile spatial acuity might be expected
      to worsen as their fingertips grow. However, concomitant CNS maturation might
      result in more efficient perceptual processing, counteracting the effect of
      fingertip growth on tactile acuity. To investigate, we conducted a cross
      sectional study, testing 116 participants ranging in age from 6 to 16 years on a
      precision-controlled tactile grating orientation task. We measured each
      participant's grating orientation threshold on the dominant index finger, along
      with physical properties of the fingertip: surface area, volume, sweat pore
      spacing, and temperature. We found that, as in adults, children with larger
      fingertips (at a given age) had significantly poorer acuity, yet paradoxically
      acuity did not worsen significantly with age. We propose that finger growth
      during development results in a gradual decline in innervation density as
      receptive fields reposition to cover an expanding skin surface. At the same time,
      central maturation presumably enhances perceptual processing. 

PMID- 24454677
TI  - PDGF, NT-3 and IGF-2 in combination induced transdifferentiation of muscle
      derived stem cells into Schwann cell-like cells.
AB  - Muscle-derived stem cells (MDSCs) are multipotent stem cells with a remarkable
      long-term self-renewal and regeneration capacity. Here, we show that postnatal
      MDSCs could be transdifferentiated into Schwann cell-like cells upon the combined
      treatment of three neurotrophic factors (PDGF, NT-3 and IGF-2). The
      transdifferentiation of MDSCs was initially induced by Schwann cell (SC)
      conditioned medium. MDSCs adopted a spindle-like morphology similar to SCs after
      the transdifferentiation. Immunocytochemistry and immunoblot showed clearly that
      the SC markers S100, GFAP and p75 were expressed highly only after the
      transdifferentiation. Flow cytometry assay showed that the portion of S100
      expressed cells was more than 60 percent and over one fourth of the
      transdifferentiated cells expressed all the three SC markers, indicating an
      efficient transdifferentiation. We then tested neurotrophic factors in the
      conditioned medium and found it was PDGF, NT-3 and IGF-2 in combination that
      conducted the transdifferentiation. Our findings demonstrate that it is possible
      to use specific neurotrophic factors to transdifferentiate MDSCs into Schwann
      cell-like cells, which might be therapeutically useful for clinical applications.

PMID- 24454678
TI  - A qualitative exploration of workarounds related to the implementation of
      national electronic health records in early adopter mental health hospitals.
AB  - AIMS: To investigate the perceptions and reported practices of mental health
      hospital staff using national hospital electronic health records (EHRs) in order
      to inform future implementations, particularly in acute mental health settings.
      METHODS: Thematic analysis of interviews with a wide range of clinical,
      information technology (IT), managerial and other staff at two early adopter
      mental health National Health Service (NHS) hospitals in London, UK, implementing
      national EHRs. RESULTS: We analysed 33 interviews. We first sought out examples
      of workarounds, such as delayed data entry, entering data in wrong places and
      individuals using the EHR while logged in as a colleague, then identified
      possible reasons for the reported workarounds. Our analysis identified four main
      categories of factors contributing to workarounds (i.e., operational, cultural,
      organisational and technical). Operational factors included poor system
      integration with existing workflows and the system not meeting users' perceived
      needs. Cultural factors involved users' competence with IT and resistance to
      change. Organisational factors referred to insufficient organisational resources
      and training, while technical factors included inadequate local technical
      infrastructure. Many of these factors, such as integrating the EHR system with
      day-to-day operational processes, staff training and adequate local IT
      infrastructure, were likely to apply to system implementations in various
      settings, but we also identified factors that related particularly to
      implementing EHRs in mental health hospitals, for example: EHR system
      incompatibility with IT systems used by mental health-related sectors, notably
      social services; the EHR system lacking specific, mental health functionalities
      and options; and clinicians feeling unable to use computers while attending to
      distressed psychiatric patients. CONCLUSIONS: A better conceptual model of
      reasons for workarounds should help with designing, and supporting the
      implementation and adoption of, EHRs for use in hospital mental health settings.

PMID- 24454679
TI  - Comparison of RNA-Seq and microarray in transcriptome profiling of activated T
      cells.
AB  - To demonstrate the benefits of RNA-Seq over microarray in transcriptome
      profiling, both RNA-Seq and microarray analyses were performed on RNA samples
      from a human T cell activation experiment. In contrast to other reports, our
      analyses focused on the difference, rather than similarity, between RNA-Seq and
      microarray technologies in transcriptome profiling. A comparison of data sets
      derived from RNA-Seq and Affymetrix platforms using the same set of samples
      showed a high correlation between gene expression profiles generated by the two
      platforms. However, it also demonstrated that RNA-Seq was superior in detecting
      low abundance transcripts, differentiating biologically critical isoforms, and
      allowing the identification of genetic variants. RNA-Seq also demonstrated a
      broader dynamic range than microarray, which allowed for the detection of more
      differentially expressed genes with higher fold-change. Analysis of the two
      datasets also showed the benefit derived from avoidance of technical issues
      inherent to microarray probe performance such as cross-hybridization, non
      specific hybridization and limited detection range of individual probes. Because
      RNA-Seq does not rely on a pre-designed complement sequence detection probe, it
      is devoid of issues associated with probe redundancy and annotation, which
      simplified interpretation of the data. Despite the superior benefits of RNA-Seq,
      microarrays are still the more common choice of researchers when conducting
      transcriptional profiling experiments. This is likely because RNA-Seq sequencing
      technology is new to most researchers, more expensive than microarray, data
      storage is more challenging and analysis is more complex. We expect that once
      these barriers are overcome, the RNA-Seq platform will become the predominant
      tool for transcriptome analysis. 

PMID- 24454680
TI  - Exposure to perfluorooctane sulfonate in utero reduces testosterone production in
      rat fetal Leydig cells.
AB  - BACKGROUND: Perfluorooctane sulfonate (PFOS) is a synthetic material that has
      been widely used in industrial applications for decades. Exposure to PFOS has
      been associated with decreased adult testosterone level, and Leydig cell
      impairment during the time of adulthood. However, little is known about PFOS
      effects in utero on fetal Leydig cells (FLC). METHODS AND RESULTS: The present
      study investigated effects of PFOS on FLC function. Pregnant Sprague Dawley
      female rats received vehicle (0.05% Tween20) or PFOS (5, 20 mg/kg) by oral gavage
      from gestational day (GD) 11-19. At GD20, testosterone (T) production, FLC
      numbers and ultrastructure, testicular gene and protein expression levels were
      examined. The results indicate that exposures to PFOS have affected FLC function
      as evidenced by decreased T production, impaired FLC, reduced FLC number, and
      decreased steroidogenic capacity and cholesterol level in utero. CONCLUSION: The
      present study shows that PFOS is an endocrine disruptor of male reproductive
      system as it causes reduction of T production and impairment of rat fetal Leydig
      cells.

PMID- 24454681
TI  - The degree of segmental aneuploidy measured by total copy number abnormalities
      predicts survival and recurrence in superficial gastroesophageal adenocarcinoma.
AB  - BACKGROUND: Prognostic biomarkers are needed for superficial gastroesophageal
      adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although
      recurrent mutations have been characterized in EAC, little is known about their
      clinical and prognostic significance. Aneuploidy is predictive of clinical
      outcome in many malignancies but has not been evaluated in superficial EAC.
      METHODS: We quantified copy number changes in 41 superficial EAC using Affymetrix
      SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and
      calculated the total copy number abnormality (CNA) count for each tumor as a
      measure of aneuploidy. We correlated CNA count with overall survival and time to
      first recurrence in univariate and multivariate analyses. RESULTS: Recurrent
      segmental gains and losses involved multiple genes, including: HER2, EGFR, MET,
      CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent
      losses). There was a 40-fold variation in CNA count across all cases. Tumors with
      the lowest and highest quartile CNA count had significantly better overall
      survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those
      with intermediate CNA counts. These associations persisted when controlling for
      other prognostic variables. SIGNIFICANCE: SNP arrays facilitate the assessment of
      recurrent chromosomal gain and loss and allow high resolution, quantitative
      assessment of segmental aneuploidy (total CNA count). The non-monotonic
      association of segmental aneuploidy with survival has been described in other
      tumors. The degree of aneuploidy is a promising prognostic biomarker in a
      potentially curable form of EAC.

PMID- 24454682
TI  - Microarray analysis of the Ler regulon in enteropathogenic and enterohaemorrhagic
      Escherichia coli strains.
AB  - The type III protein secretion system is an important pathogenicity factor of
      enteropathogenic and enterohaemorrhagic Escherichia coli pathotypes. The genes
      encoding this apparatus are located on a pathogenicity island (the locus of
      enterocyte effacement) and are transcriptionally activated by the master
      regulator Ler. In each pathotype Ler is also known to regulate genes located
      elsewhere on the chromosome, but the full extent of the Ler regulon is unclear,
      especially for enteropathogenic E. coli. The Ler regulon was defined for two
      strains of E. coli: E2348/69 (enteropathogenic) and EDL933 (enterohaemorrhagic)
      in mid and late log phases of growth by DNA microarray analysis of the
      transcriptomes of wild-type and ler mutant versions of each strain. In both
      strains the Ler regulon is focused on the locus of enterocyte effacement - all
      major transcriptional units of which are activated by Ler, with the sole
      exception of the LEE1 operon during mid-log phase growth in E2348/69. However,
      the Ler regulon does extend more widely and also includes unlinked pathogenicity
      genes: in E2348/69 more than 50 genes outside of this locus were regulated,
      including a number of known or potential pathogenicity determinants; in EDL933
      only 4 extra-LEE genes, again including known pathogenicity factors, were
      activated. In E2348/69, where the Ler regulon is clearly growth phase dependent,
      a number of genes including the plasmid-encoded regulator operon perABC, were
      found to be negatively regulated by Ler. Negative regulation by Ler of PerC,
      itself a positive regulator of the ler promoter, suggests a negative feedback
      loop involving these proteins. 

PMID- 24454683
TI  - Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by
      replicative and translesion polymerases, revealing their potential to lead to
      genetic change.
AB  - Recent research indicates that hundreds of thousands of G-rich sequences within
      the human genome have the potential to form secondary structures known as G
      quadruplexes. Telomeric regions, consisting of long arrays of TTAGGG/AATCCC
      repeats, are among the most likely areas in which these structures might form.
      Since G-quadruplexes assemble from certain G-rich single-stranded sequences, they
      might arise when duplex DNA is unwound such as during replication.
      Coincidentally, these bulky structures when present in the DNA template might
      also hinder the action of DNA polymerases. In this study, single-stranded
      telomeric templates with the potential to form G-quadruplexes were examined for
      their effects on a variety of replicative and translesion DNA polymerases from
      humans and lower organisms. Our results demonstrate that single-stranded
      templates containing four telomeric GGG runs fold into intramolecular G
      quadruplex structures. These intramolecular G quadruplexes are somewhat dynamic
      in nature and stabilized by increasing KCl concentrations and decreasing
      temperatures. Furthermore, the presence of these intramolecular G-quadruplexes in
      the template dramatically inhibits DNA synthesis by various DNA polymerases,
      including the human polymerase delta employed during lagging strand replication
      of G-rich telomeric strands and several human translesion DNA polymerases
      potentially recruited to sites of replication blockage. Notably, misincorporation
      of nucleotides is observed when certain translesion polymerases are employed on
      substrates containing intramolecular G-quadruplexes, as is extension of the
      resulting mismatched base pairs upon dynamic unfolding of this secondary
      structure. These findings reveal the potential for blockage of DNA replication
      and genetic changes related to sequences capable of forming intramolecular G
      quadruplexes. 

PMID- 24454684
TI  - Targeting Bcl-2/Bcl-XL induces antitumor activity in uveal melanoma patient
      derived xenografts.
AB  - PURPOSE: Uveal melanoma (UM) is associated with a high risk of metastases and
      lack of efficient therapies. Reduced capacity for apoptosis induction by
      chemotherapies is one obstacle to efficient treatments. Human UM is characterized
      by high expression of the anti-apoptotic protein Bcl-2. Consequently, regulators
      of apoptosis such as Bcl-2 family inhibitors may constitute an attractive
      approach to UM therapeutics. In this aim, we have investigated the efficacy of
      the Bcl-2/Bcl-XL inhibitor S44563 on 4 UM Patient-Derived Xenografts (PDXs) and
      derived-cell lines. EXPERIMENTAL DESIGN: Four well characterized UM PDXs were
      used for in vivo experiments. S44563 was administered alone or combined with
      fotemustine either concomitantly or after the alkylating agent. Bcl-2, Bcl-XL,
      and Mcl-1 expressions after S44563 administration were evaluated by
      immunohistochemistry (IHC). RESULTS: S44563 administered alone by at 50 and 100
      mg/kg i.p. induced a significant tumour growth inhibition in only one xenograft
      model with a clear dose effect. However, when S44563 was concomitantly
      administered with fotemustine, we observed a synergistic activity in 3 out of the
      4 tested models. In addition, S44563 administered after fotemustine induced a
      tumour growth delay in 2 out of 3 tested xenografts. Finally, IHC analyses showed
      that Bcl-2, Bcl-XL, and Mcl-1 expression were not modified after S44563
      administration. CONCLUSION: The novel anti-apoptotic experimental compound
      S44563, despite a relative low efficacy when administered alone, increased the
      efficacy of fotemustine in either concomitant or sequential combinations or
      indeed subsequent to fotemustine. These data support further exploration of
      potential therapeutic effect of Bcl-2/Bcl-xl inhibition in human UM.

PMID- 24454685
TI  - Systematic review of health disparities for cardiovascular diseases and
      associated factors among American Indian and Alaska Native populations.
AB  - BACKGROUND: American Indians and Alaska Native (AI/AN) populations experience
      significant health disparities compared to non-Hispanic white populations.
      Cardiovascular disease and related risk factors are increasingly recognized as
      growing indicators of global health disparities. However, comparative reports on
      disparities among this constellation of diseases for AI/AN populations have not
      been systematically reviewed. OBJECTIVES: We performed a literature review on the
      prevalence of diabetes, metabolic syndrome, dyslipidemia, obesity, hypertension,
      and cardiovascular disease; and associated morbidity and mortality among AI/AN.
      DATA SOURCES: A total of 203 articles were reviewed, of which 31 met study
      criteria for inclusion. Searches were performed on PUBMED, MEDLINE, the CDC MMWR,
      and the Indian Health Services. STUDY ELIGIBILITY CRITERIA: Published literature
      that were published within the last fifteen years and provided direct comparisons
      between AI/AN to non-AI/AN populations were included. STUDY APPRAISAL AND
      SYNTHESIS METHODS: We abstracted data on study design, data source, AI/AN
      population, comparison group, and. outcome measures. A descriptive synthesis of
      primary findings is included. RESULTS: Rates of obesity, diabetes, cardiovascular
      disease, and metabolic syndrome are clearly higher for AI/AN populations.
      Hypertension and hyperlipidemia differences are more equivocal. Our analysis also
      revealed that there are likely regional and gender differences in the degree of
      disparities observed. LIMITATIONS: Studies using BRFSS telephone surveys
      administered in English may underestimate disparities. Many AI/AN do not have
      telephones and/or speak English. Regional variability makes national surveys
      difficult to interpret. Finally, studies using self-reported data may not be
      accurate. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Profound health
      disparities in cardiovascular diseases and associated risk factors for AI/AN
      populations persist, perhaps due to low socioeconomic status and access to
      quality healthcare. Successful programs will address social determinants and
      increase healthcare access. Community-based outreach to bring health services to
      the most vulnerable may also be very helpful in this effort. SYSTEMATIC REVIEW
      REGISTRATION NUMBER: N/A.

PMID- 24454686
TI  - A new sebecid from the paleogene of Brazil and the crocodyliform radiation after
      the K-Pg boundary.
AB  - A new crocodyliform, Sahitisuchus fluminensis gen. et sp. nov., is described
      based on a complete skull, lower jaw and anterior cervical vertebrae collected in
      the Sao Jose de Itaborai Basin of Rio de Janeiro, Brazil. The specimen is one of
      the best preserved crocodyliforms from Paleocene deposits recovered so far and
      represents a sebecosuchian, one of the few clades that survived the Cretaceous
      Paleogene biotic crisis. The new taxon is found in the same deposit as an
      alligatoroid, a group that experienced large diversification in the Paleogene.
      The sebecosuchian record suggests that after the Cretaceous-Paleogene biotic
      crisis, the less specialized members of this clade characterized by a higher
      number of teeth compared to the baurusuchid sebecosuchians survived, some having
      terrestrial habits while others developed a semi-aquatic life style (e.g.,
      Lorosuchus). Starting in the Eocene, sebecid sebecosuchians became specialized
      with a more accentuated oreinirostry as observed in Sebecus and in Langstonia,
      but not showing the typical reduced dentition developed by the Cretaceous
      baurusuchid sebecosuchians. The basal position of Barinasuchus arveloi, a high
      snouted Miocene sebecid, indicates the occurrence of an independent lineage
      sometime after the K-Pg biotic crisis that developed accentuated oreinirostry,
      suggesting a more complex history of the post-K-Pg crocodyliform radiation. 

PMID- 24454687
TI  - A model of two-way selection system for human behavior.
AB  - Two-way selection is a common phenomenon in nature and society. It appears in the
      processes like choosing a mate between men and women, making contracts between
      job hunters and recruiters, and trading between buyers and sellers. In this
      paper, we propose a model of two-way selection system, and present its analytical
      solution for the expectation of successful matching total and the regular pattern
      that the matching rate trends toward an inverse proportion to either the ratio
      between the two sides or the ratio of the state total to the smaller group's
      people number. The proposed model is verified by empirical data of the
      matchmaking fairs. Results indicate that the model well predicts this typical
      real-world two-way selection behavior to the bounded error extent, thus it is
      helpful for understanding the dynamics mechanism of the real-world two-way
      selection system. 

PMID- 24454688
TI  - Structural and functional analyses of a sterol carrier protein in Spodoptera
      litura.
AB  - BACKGROUNDS: In insects, cholesterol is one of the membrane components in cells
      and a precursor of ecdysteroid biosynthesis. Because insects lack two key
      enzymes, squalene synthase and lanosterol synthase, in the cholesterol
      biosynthesis pathway, they cannot autonomously synthesize cholesterol de novo
      from simple compounds and therefore have to obtain sterols from their diet.
      Sterol carrier protein (SCP) is a cholesterol-binding protein responsible for
      cholesterol absorption and transport. RESULTS: In this study, a model of the
      three-dimensional structure of SlSCPx-2 in Spodoptera litura, a destructive
      polyphagous agricultural pest insect in tropical and subtropical areas, was
      constructed. Docking of sterol and fatty acid ligands to SlSCPx-2 and ANS
      fluorescent replacement assay showed that SlSCPx-2 was able to bind with
      relatively high affinities to cholesterol, stearic acid, linoleic acid,
      stigmasterol, oleic acid, palmitic acid and arachidonate, implying that SlSCPx
      may play an important role in absorption and transport of these cholesterol and
      fatty acids from host plants. Site-directed mutation assay of SlSCPx-2 suggests
      that amino acid residues F53, W66, F89, F110, I115, T128 and Q131 are critical
      for the ligand-binding activity of the SlSCPx-2 protein. Virtual ligand screening
      resulted in identification of several lead compounds which are potential
      inhibitors of SlSCPx-2. Bioassay for inhibitory effect of five selected compounds
      showed that AH-487/41731687, AG-664/14117324, AG-205/36813059 and AG-205/07775053
      inhibited the growth of S. litura larvae. CONCLUSIONS: Compounds AH-487/41731687,
      AG-664/14117324, AG-205/36813059 and AG-205/07775053 selected based on structural
      modeling showed binding affinity to SlSCPx-2 protein and inhibitory effect on the
      growth of S. litura larvae.

PMID- 24454689
TI  - The genome sequence of the fungal pathogen Fusarium virguliforme that causes
      sudden death syndrome in soybean.
AB  - Fusarium virguliforme causes sudden death syndrome (SDS) of soybean, a disease of
      serious concern throughout most of the soybean producing regions of the world.
      Despite the global importance, little is known about the pathogenesis mechanisms
      of F. virguliforme. Thus, we applied Next-Generation DNA Sequencing to reveal the
      draft F. virguliforme genome sequence and identified putative pathogenicity genes
      to facilitate discovering the mechanisms used by the pathogen to cause this
      disease. METHODOLOGY/PRINCIPAL FINDINGS: We have generated the draft genome
      sequence of F. virguliforme by conducting whole-genome shotgun sequencing on a
      454 GS-FLX Titanium sequencer. Initially, single-end reads of a 400-bp shotgun
      library were assembled using the PCAP program. Paired end sequences from 3 and 20
      Kb DNA fragments and approximately 100 Kb inserts of 1,400 BAC clones were used
      to generate the assembled genome. The assembled genome sequence was 51 Mb. The
      N50 scaffold number was 11 with an N50 Scaffold length of 1,263 Kb. The AUGUSTUS
      gene prediction program predicted 14,845 putative genes, which were annotated
      with Pfam and GO databases. Gene distributions were uniform in all but one of the
      major scaffolds. Phylogenic analyses revealed that F. virguliforme was closely
      related to the pea pathogen, Nectria haematococca. Of the 14,845 F. virguliforme
      genes, 11,043 were conserved among five Fusarium species: F. virguliforme, F.
      graminearum, F. verticillioides, F. oxysporum and N. haematococca; and 1,332 F.
      virguliforme-specific genes, which may include pathogenicity genes. Additionally,
      searches for candidate F. virguliforme pathogenicity genes using gene sequences
      of the pathogen-host interaction database identified 358 genes. CONCLUSIONS: The
      F. virguliforme genome sequence and putative pathogenicity genes presented here
      will facilitate identification of pathogenicity mechanisms involved in SDS
      development. Together, these resources will expedite our efforts towards
      discovering pathogenicity mechanisms in F. virguliforme. This will ultimately
      lead to improvement of SDS resistance in soybean.

PMID- 24454690
TI  - Stent-assisted coiling versus coiling in treatment of intracranial aneurysm: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Stent-assisted coiling was initially invented for wide
      neck aneurysms, but is now used for smaller berry aneurysms. The aim of this
      study was to compare the safety and efficiency of stent-assisted coiling with
      conventional coiling in treatment of intracranial aneurysms. METHODS: A meta
      analysis of studies that compared stent-assisted coiling with coiling only was
      conducted by searching English literatures via Pubmed, Medline and Cochrane
      Library databases without restricting the publication year. The primary outcomes
      in this study were immediate occlusion, progressive thrombosis rate, all
      complication rate and angiographic recurrence. The secondary outcomes examined
      were packing density, mortality, permanent complication and thromboembolic
      complication rate. RESULTS: Ten retrospective cohort studies were included. There
      is currently only one unfinished randomized study. Although the stent-assisted
      coiling group tended to show a lower initial occlusion rate than that of the
      coiling-only group (57.6% versus 68.7%; OR, 0.66; 95% CI, 0.30-1.44; P = 0.30),
      it achieved a significantly higher progressive thrombosis rate during follow up
      compared to that of the coiling only group (37.5% versus 19.4%; OR, 2.75; 95% CI,
      1.95-3.86; P<0.00001) and a significantly lower recurrence rate (16.2% versus
      34.4%; OR, 0.35; 95% CI, 0.25-0.49; P<0.00001). With respect to safety concerns,
      the all-complication rate (17.6% versus 15.9%; OR, 1.12; 95% CI, 0.77-1.62; P =
      0.56), mortality rate (9.1% versus 2.6%; OR, 2.31; 95% CI, 0.68-7.82; P = 0.18),
      permanent complication rate (5.6% versus 3.9%; OR, 1.52; 95% CI, 0.96-2.41; P =
      0.08) and thromboembolic complication rate (4.2% versus 4.9%; OR, 0.99; 95% CI,
      0.41-2.38; P = 0.97) did not show significant difference between the two groups.
      CONCLUSIONS: Stent-assisted coiling has a lower recurrence rate than conventional
      coiling. Analysis of complication events did not show any significant difference
      between the two methods. Despite the findings reported herein, further validation
      by well-designed prospective studies is needed.

PMID- 24454691
TI  - Metabolomics coupled with multivariate data and pathway analysis on potential
      biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo
      alkaloid.
AB  - Metabolomics, the systematic analysis of potential metabolites in a biological
      specimen, has been increasingly applied to discovering biomarkers, identifying
      perturbed pathways, measuring therapeutic targets, and discovering new drugs. By
      analyzing and verifying the significant difference in metabolic profiles and
      changes of metabolite biomarkers, metabolomics enables us to better understand
      substance metabolic pathways which can clarify the mechanism of Traditional
      Chinese Medicines (TCM). Corydalis yanhusuo alkaloid (CA) is a major component of
      Qizhiweitong (QZWT) prescription which has been used for treating gastric ulcer
      for centuries and its mechanism remains unclear completely. Metabolite profiling
      was performed by high-performance liquid chromatography combined with time-of
      flight mass spectrometry (HPLC/ESI-TOF-MS) and in conjunction with multivariate
      data analysis and pathway analysis. The statistic software Mass Profiller
      Prossional (MPP) and statistic method including ANOVA and principal component
      analysis (PCA) were used for discovering novel potential biomarkers to clarify
      mechanism of CA in treating acid injected rats with gastric ulcer. The changes in
      metabolic profiling were restored to their base-line values after CA treatment
      according to the PCA score plots. Ten different potential biomarkers and seven
      key metabolic pathways contributing to the treatment of gastric ulcer were
      discovered and identified. Among the pathways, sphingophospholipid metabolism and
      fatty acid metabolism related network were acutely perturbed. Quantitative real
      time polymerase chain reaction (RT-PCR) analysis were performed to evaluate the
      expression of genes related to the two pathways for verifying the above results.
      The results show that changed biomarkers and pathways may provide evidence to
      insight into drug action mechanisms and enable us to increase research
      productivity toward metabolomics drug discovery. 

PMID- 24454692
TI  - Polymicrobial bloodstream infection in neonates: microbiology, clinical
      characteristics, and risk factors.
AB  - BACKGROUND: Polymicrobial bloodstream infections (PBSIs) have been associated
      with complex underlying medical conditions and a high incidence of specific
      microorganisms in several settings, but the relevant data are scarce in neonates.
      METHODS: Positive blood cultures from January 2004 to December 2011 in the
      neonatal intensive care unit (NICU) of Chang Gung Memorial Hospital (CGMH) were
      reviewed. Each neonate with PBSI (case episode) was matched to two episodes of
      monomicrobial BSI (control episode) by birth weight, gestational age and gender.
      Records were reviewed to compare their underlying medical conditions, organisms
      isolated, adequacy of therapy, clinical characteristics and outcomes. RESULTS:
      Forty-five episodes of PBSI (4.4% of all neonatal BSIs) were identified in 43
      neonates. Gram-negative organisms constituted 59.8% of all PBSI pathogens, and 33
      (73.3%) of PBSIs were caused by at least one Gram-negative organism. PBSIs were
      significantly more likely to be the recurrent episode and have endotracheal tube
      in place. No significant difference was found between PBSIs and controls in terms
      of demographics and most chronic conditions. PBSIs were significantly associated
      with a higher severity of illness, a longer duration of septic symptoms, and a
      higher rate of modification of antimicrobial regimens than monomicrobial BSIs.
      However, the sepsis-attributable mortality rates were comparable between these
      two groups. CONCLUSIONS: In the NICU, PBSIs were more often caused by Gram
      negative bacilli, and often occurred in neonates without any chronic conditions.
      The clinical significance of PBSIs included a more severe illness, longer
      duration of septic symptoms and a higher rate of modification of antimicrobial
      regimens.

PMID- 24454694
TI  - Effect of Joule heating and thermal radiation in flow of third grade fluid over
      radiative surface.
AB  - This article addresses the boundary layer flow and heat transfer in third grade
      fluid over an unsteady permeable stretching sheet. The transverse magnetic and
      electric fields in the momentum equations are considered. Thermal boundary layer
      equation includes both viscous and Ohmic dissipations. The related nonlinear
      partial differential system is reduced first into ordinary differential system
      and then solved for the series solutions. The dependence of velocity and
      temperature profiles on the various parameters are shown and discussed by
      sketching graphs. Expressions of skin friction coefficient and local Nusselt
      number are calculated and analyzed. Numerical values of skin friction coefficient
      and Nusselt number are tabulated and examined. It is observed that both velocity
      and temperature increases in presence of electric field. Further the temperature
      is increased due to the radiation parameter. Thermal boundary layer thickness
      increases by increasing Eckert number. 

PMID- 24454693
TI  - Loss of social behaviours in populations of Pseudomonas aeruginosa infecting
      lungs of patients with cystic fibrosis.
AB  - Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing
      persistent and frequently fatal infections of the lung in patients with cystic
      fibrosis. Isolates from chronic infections differ from laboratory and
      environmental strains in a range of traits and this is widely interpreted as the
      result of adaptation to the lung environment. Typically, chronic strains carry
      mutations in global regulation factors that could effect reduced expression of
      social traits, raising the possibility that competitive dynamics between
      cooperative and selfish, cheating strains could also drive changes in P.
      aeruginosa infections. We compared the expression of cooperative traits - biofilm
      formation, secretion of exo-products and quorum sensing (QS) - in P. aeruginosa
      isolates that were estimated to have spent different lengths of time in the lung
      based on clinical information. All three exo-products involved in nutrient
      acquisition were produced in significantly smaller quantities with increased
      duration of infection, and patterns across four QS signal molecules were
      consistent with accumulation over time of mutations in lasR, which are known to
      disrupt the ability of cells to respond to QS signal. Pyocyanin production, and
      the proportion of cells in biofilm relative to motile, free-living cells in
      liquid culture, did not change. Overall, our results confirm that the loss of
      social behaviour is a consistent trend with time spent in the lung and suggest
      that social dynamics are potentially relevant to understanding the behaviour of
      P. aeruginosa in lung infections. 

PMID- 24454695
TI  - Arsenic sulfide promotes apoptosis in retinoid acid resistant human acute
      promyelocytic leukemic NB4-R1 cells through downregulation of SET protein.
AB  - Tetra-arsenic tetra-sulfide (As4S4) is an arsenic compound with anti-tumor
      activity, especially in acute promyelocytic leukemia (APL) that are resistant to
      retinoic acid (RA). Although recent studies revealed that the therapeutic action
      of As4S4 is closely associated with the induction of cellular apoptosis, the
      exact molecular mechanism of action of As4S4 in RA-resistant APL remains to be
      clarified. In this study, we found that As4S4-induced apoptosis was accompanied
      by reduced mRNA and protein expression of SET gene in RA-resistant NB4-R1 cells.
      Moreover, RNAi knockdown of SET gene further promoted As4S4-induced apoptosis,
      while SET over-expression inhibited it, suggesting that As4S4 induces apoptosis
      through the reduction of SET protein in NB4-R1 cells. We also demonstrated that
      the knockdown of SET gene resulted in the upregulation of protein phosphatase 2
      (PP2A) expression and the downregulation of promyelocytic leukemia and retinoic
      acid receptor alpha fusion gene (PML-RARalpha) expression, which were enhanced by
      As4S4 treatments. By contrast, over-expression of SET gene resulted in PP2A
      downregulation and PML-RARalpha upregulation, which were abolished by As4S4
      pretreatment. Since PP2A is a pro-apoptotic factor and PMLRARalpha is an anti
      apoptotic factor, our results suggest that As4S4-induced apoptosis in NB4-R1
      cells is through the downregulation of SET protein expression, which in turn
      increases PP2A and reduces PML-RARalpha expressions to lead to cell apoptosis.

PMID- 24454696
TI  - Impact of high risk drug use on hospitalization and mortality in older people
      with and without Alzheimer's disease: a national population cohort study.
AB  - BACKGROUND: Evidence is lacking about outcomes associated with the cumulative use
      of anticholinergic and sedative drugs in people with Alzheimer's disease (AD).
      This retrospective cohort study investigated the relationship between cumulative
      exposure to anticholinergic and sedative drugs and hospitalization and mortality
      in people with and without AD in Finland. METHODS: Community-dwelling people aged
      65 years and over, with AD on December 31(st) 2005 (n = 16,603) and individually
      matched (n = 16,603) comparison persons (age, sex, region of residence) were
      identified by the Social Insurance Institution of Finland. Drug utilization data
      were extracted from the Finnish National Prescription Register. Exposure to
      anticholinergic and sedative drugs was defined using the Drug Burden Index (DBI).
      Hospitalization and mortality data were extracted from national registers. Cox
      and zero-inflated negative binomial analyses were used to investigate the
      relationship between DBI and hospitalization and mortality over a one-year follow
      up. RESULTS: In total, 5.8% of people with AD and 3.7% without AD died during
      2006. For every unit increase in DBI, the adjusted hazard ratio for mortality was
      1.21 (95% confidence intervals [CI]: 1.09-1.33) among people with AD, and 1.37
      (95%CI: 1.20-1.56) among people without AD. Overall, 44.3% of people with AD and
      33.4% without AD were hospitalized. When using no DBI exposure as the reference
      group, the adjusted incidence rate ratio for length of hospital stay among high
      DBI group (>=1) in people with AD was 1.15 (95%CI: 1.05-1.26) and 1.63 (95%CI:
      1.41-1.88) in people without AD. CONCLUSION: There is a dose-response
      relationship between cumulative anticholinergic and sedative drug use and
      hospitalization and mortality in people with and without AD.

PMID- 24454697
TI  - School programs and characteristics and their influence on student BMI: findings
      from healthy passages.
AB  - BACKGROUND: Little is known about the contribution of school contextual factors
      to individual student body mass index (BMI). We set out to determine if school
      characteristics/resources: (1) are associated with student BMI; (2) explain
      racial/ethnic disparities in student BMI; and (3) explain school-level
      differences in student BMI. METHODS: Using gender-stratified multi-level modeling
      strategies we examined the association of school characteristics/resources and
      individual BMI in 4,387 5(th) graders in the Healthy Passages Longitudinal Study
      of Adolescent Health. Additionally, we examined the association of race/ethnicity
      and individual BMI as well as the between-school variance in BMI before and after
      adding individual and school characteristics to test for attenuation. RESULTS:
      The school-level median household income, but not physical activity or nutrition
      resources, was inversely associated with female BMI (beta = -0.12, CI: -0.21,
      0.02). Neither school demographics nor physical activity/nutrition resources were
      predictive of individual BMI in males. In Black females, school characteristics
      attenuated the association of race/ethnicity and BMI. Individual student
      characteristics-not school characteristics/resources-reduced the between-school
      variation in BMI in males by nearly one-third and eliminated it in females.
      CONCLUSIONS: In this cohort of 5(th) graders, school SES was inversely associated
      with female BMI while school characteristics and resources largely explained
      Black/White disparities in female weight status. Between-school differences in
      average student weight status were largely explained by the composition of the
      student body not by school characteristics or programming.

PMID- 24454698
TI  - High intensity interval training in a real world setting: a randomized controlled
      feasibility study in overweight inactive adults, measuring change in maximal
      oxygen uptake.
AB  - BACKGROUND: In research clinic settings, overweight adults undertaking HIIT (high
      intensity interval training) improve their fitness as effectively as those
      undertaking conventional walking programs but can do so within a shorter time
      spent exercising. We undertook a randomized controlled feasibility (pilot) study
      aimed at extending HIIT into a real world setting by recruiting overweight/obese,
      inactive adults into a group based activity program, held in a community park.
      METHODS: Participants were allocated into one of three groups. The two
      interventions, aerobic interval training and maximal volitional interval
      training, were compared with an active control group undertaking walking based
      exercise. Supervised group sessions (36 per intervention) were held outdoors.
      Cardiorespiratory fitness was measured using VO2max (maximal oxygen uptake,
      results expressed in ml/min/kg), before and after the 12 week interventions.
      RESULTS: On ITT (intention to treat) analyses, baseline (N = 49) and exit (N =
      39) [Formula: see text]O2 was 25.3+/-4.5 and 25.3+/-3.9, respectively.
      Participant allocation and baseline/exit VO2max by group was as follows: Aerobic
      interval training N =  16, 24.2+/-4.8/25.6+/-4.8; maximal volitional interval
      training N = 16, 25.0+/-2.8/25.2+/-3.4; walking N = 17, 26.5+/-5.3/25.2+/-3.6.
      The post intervention change in VO2max was +1.01 in the aerobic interval
      training, -0.06 in the maximal volitional interval training and -1.03 in the
      walking subgroups. The aerobic interval training subgroup increased VO2max
      compared to walking (p = 0.03). The actual (observed, rather than prescribed)
      time spent exercising (minutes per week, ITT analysis) was 74 for aerobic
      interval training, 45 for maximal volitional interval training and 116 for
      walking (p =  0.001). On descriptive analysis, the walking subgroup had the
      fewest adverse events. CONCLUSIONS: In contrast to earlier studies, the
      improvement in cardiorespiratory fitness in a cohort of overweight/obese
      participants undertaking aerobic interval training in a real world setting was
      modest. The most likely reason for this finding relates to reduced adherence to
      the exercise program, when moving beyond the research clinic setting. TRIAL
      REGISTRATION: ACTR.org.au ACTRN12610000295044.

PMID- 24454699
TI  - Improving the Manchester Triage System for pediatric emergency care: an
      international multicenter study.
AB  - OBJECTIVES: This multicenter study examines the performance of the Manchester
      Triage System (MTS) after changing discriminators, and with the addition use of
      abnormal vital sign in patients presenting to pediatric emergency departments
      (EDs). DESIGN: International multicenter study. SETTINGS: EDs of two hospitals in
      The Netherlands (2006-2009), one in Portugal (November-December 2010), and one in
      UK (June-November 2010). PATIENTS: Children (<16 years) triaged with the MTS who
      presented at the ED. METHODS: Changes to discriminators (MTS 1) and the value of
      including abnormal vital signs (MTS 2) were studied to test if this would
      decrease the number of incorrect assignment. Admission to hospital using the new
      MTS was compared with those in the original MTS. Likelihood ratios, diagnostic
      odds ratios (DORs), and c-statistics were calculated as measures for performance
      and compared with the original MTS. To calculate likelihood ratios and DORs, the
      MTS had to be dichotomized in low urgent and high urgent. RESULTS: 60,375
      patients were included, of whom 13% were admitted. When MTS 1 was used, admission
      to hospital increased from 25% to 29% for MTS 'very urgent' patients and remained
      similar in lower MTS urgency levels. The diagnostic odds ratio improved from 4.8
      (95%CI 4.5-5.1) to 6.2 (95%CI 5.9-6.6) and the c-statistic remained 0.74. MTS 2
      did not improve the performance of the MTS. CONCLUSIONS: MTS 1 performed slightly
      better than the original MTS. The use of vital signs (MTS 2) did not improve the
      MTS performance.

PMID- 24454700
TI  - Remnant trees affect species composition but not structure of tropical second
      growth forest.
AB  - Remnant trees, spared from cutting when tropical forests are cleared for
      agriculture or grazing, act as nuclei of forest regeneration following field
      abandonment. Previous studies on remnant trees were primarily conducted in active
      pasture or old fields abandoned in the previous 2-3 years, and focused on
      structure and species richness of regenerating forest, but not species
      composition. Our study is among the first to investigate the effects of remnant
      trees on neighborhood forest structure, biodiversity, and species composition 20
      years post-abandonment. We compared the woody vegetation around individual
      remnant trees to nearby plots without remnant trees in the same second-growth
      forests ("control plots"). Forest structure beneath remnant trees did not differ
      significantly from control plots. Species richness and species diversity were
      significantly higher around remnant trees. The species composition around remnant
      trees differed significantly from control plots and more closely resembled the
      species composition of nearby old-growth forest. The proportion of old-growth
      specialists and generalists around remnant trees was significantly greater than
      in control plots. Although previous studies show that remnant trees may initially
      accelerate secondary forest growth, we found no evidence that they locally affect
      stem density, basal area, and seedling density at later stages of regrowth.
      Remnant trees do, however, have a clear effect on the species diversity,
      composition, and ecological groups of the surrounding woody vegetation, even
      after 20 years of forest regeneration. To accelerate the return of diversity and
      old-growth forest species into regrowing forest on abandoned land, landowners
      should be encouraged to retain remnant trees in agricultural or pastoral fields. 

PMID- 24454701
TI  - Maternal mortality in India: causes and healthcare service use based on a
      nationally representative survey.
AB  - BACKGROUND: Data on cause-specific mortality, skilled birth attendance, and
      emergency obstetric care access are essential to plan maternity services. We
      present the distribution of India's 2001-2003 maternal mortality by cause and
      uptake of emergency obstetric care, in poorer and richer states. METHODS AND
      FINDINGS: The Registrar General of India surveyed all deaths occurring in 2001
      2003 in 1.1 million nationally representative homes. Field staff interviewed
      household members about events that preceded the death. Two physicians
      independently assigned a cause of death. Narratives for all maternal deaths were
      coded for variables on healthcare uptake. Distribution of number of maternal
      deaths, cause-specific mortality and uptake of healthcare indicators were
      compared for poorer and richer states. There were 10,041 all-cause deaths in
      women age 15-49 years, of which 1096 (11.1%) were maternal deaths. Based on 2004
      2006 SRS national MMR estimates of 254 deaths per 100,000 live births, we
      estimated rural areas of poorer states had the highest MMR (397, 95%CI 385-410)
      compared to the lowest MMR in urban areas of richer states (115, 95%CI 85-146).
      We estimated 69,400 maternal deaths in India in 2005. Three-quarters of maternal
      deaths were clustered in rural areas of poorer states, although these regions
      have only half the estimated live births in India. Most maternal deaths were
      attributed to direct obstetric causes (82%). There was no difference in the major
      causes of maternal deaths between poorer and richer states. Two-thirds of women
      died seeking some form of healthcare, most seeking care in a critical medical
      condition. Rural areas of poorer states had proportionately lower access and
      utilization to healthcare services than the urban areas; however this rural-urban
      difference was not seen in richer states. CONCLUSIONS: Maternal mortality and
      poor access to healthcare is disproportionately higher in rural populations of
      the poorer states of India.

PMID- 24454703
TI  - Increasing coverage in mass drug administration for lymphatic filariasis
      elimination in an urban setting: a study of Malindi Town, Kenya.
AB  - INTRODUCTION: Implementation of Mass Drug Administration (MDA) in urban settings
      is an obstacle to Lymphatic Filariasis (LF) elimination. No urban-specific
      guidelines on MDA in urban areas exist. Malindi district urban area had received
      4 MDA rounds by the time the current study was implemented. Programme data showed
      average treatment coverage of 28.4% (2011 MDA), far below recommended minimum of
      65-80%. METHODS: To identify, design and test strategies for increased treatment
      coverage in urban areas, a quasi-experimental study was conducted in Malindi
      urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were
      purposively selected. In the pre-test phase, 947 household heads sampled using
      systematic random method were interviewed for quantitative data. For qualitative
      data, 12 Focus Group Discussions (FGDs) with single sex adult and youth male and
      female groups and 3 with community drug distributors (CDDs) were conducted. Forty
      in-depth interviews with opinion leaders and self-administered questionnaires
      with District Public Health officers purposively selected were carried out. The
      quantitative data were analyzed using SPSS version 16 and statistical
      significance assessed by chi(2) test.The qualitative data were analyzed manually
      according to study's themes. RESULTS AND DISCUSSION: The identified strategies
      were implemented prior to and during 2012 MDA in two sub-locations (experimental)
      while in the third (control), usual MDA strategies were applied. In the post-test
      phase, 2012 MDA coverage in experimental and control sub-locations was
      comparatively assessed for effect of the newly designed strategies on urban MDA.
      Results indicated improved treatment coverage in experimental sub-locations,
      77.1% in Shella and 66.0% in Barani. Central (control) sub-location also attained
      high coverage, 70.4% indicating average treatment coverage of 71%. CONCLUSION:
      The identified strategies contributed to increased treatment coverage in
      experimental sites and should be applied in urban areas. Due to closeness of
      sites, spillover effects may have contributed to increased coverage in the
      control site.

PMID- 24454702
TI  - Novel HIV-1 recombinants spreading across multiple risk groups in the United
      Kingdom: the identification and phylogeography of Circulating Recombinant Form
      (CRF) 50_A1D.
AB  - BACKGROUND: An increase in non-B HIV-1 infections among men who have sex with men
      (MSM) in the United Kingdom (UK) has created opportunities for novel recombinants
      to arise and become established. We used molecular mapping to characterize the
      importance of such recombinants to the UK HIV epidemic, in order to gain insights
      into transmission dynamics that can inform control strategies. METHODS AND
      RESULTS: A total of 55,556 pol (reverse transcriptase and protease) sequences in
      the UK HIV Drug Resistance Database were analyzed using Subtype Classification
      Using Evolutionary Algorithms (SCUEAL). Overall 72 patients shared the same A1/D
      recombination breakpoint in pol, comprising predominantly MSM but also
      heterosexuals and injecting drug users (IDUs). In six MSM, full-length single
      genome amplification of plasma HIV-1 RNA was performed in order to characterize
      the A1/D recombinant. Subtypes and recombination breakpoints were identified
      using sliding window and jumping profile hidden markov model approaches. Global
      maximum likelihood trees of gag, pol and env genes were drawn using FastTree
      version 2.1. Five of the six strains showed the same novel A1/D recombinant (8
      breakpoints), which has been classified as CRF50_A1D. The sixth strain showed a
      complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences
      were determined using Bayesian Evolutionary Analysis using Sampling Trees
      (BEAST). This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with
      subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U
      demonstrated that around the year 2000 CRF50_A1D underwent recombination with a
      subtype B strain. CONCLUSIONS: We report the identification of CRF50_A1D, a novel
      circulating recombinant that emerged in UK MSM around 1992, with subsequent
      onward transmission to heterosexuals and IDUs, and more recent recombination with
      subtype B. These findings highlight the changing dynamics of HIV transmission in
      the UK and the converging of the two previously distinct MSM and heterosexual
      epidemics.

PMID- 24454704
TI  - Does increased exercise or physical activity alter ad-libitum daily energy intake
      or macronutrient composition in healthy adults? A systematic review.
AB  - BACKGROUND: The magnitude of the negative energy balance induced by exercise may
      be reduced due to compensatory increases in energy intake. OBJECTIVE: TO ADDRESS
      THE QUESTION: Does increased exercise or physical activity alter ad-libitum daily
      energy intake or macronutrient composition in healthy adults? DATA SOURCES:
      PubMed and Embase were searched (January 1990-January 2013) for studies that
      presented data on energy and/or macronutrient intake by level of exercise,
      physical activity or change in response to exercise. Ninety-nine articles (103
      studies) were included. STUDY ELIGIBILITY CRITERIA: Primary source articles
      published in English in peer-reviewed journals. Articles that presented data on
      energy and/or macronutrient intake by level of exercise or physical activity or
      changes in energy or macronutrient intake in response to acute exercise or
      exercise training in healthy (non-athlete) adults (mean age 18-64 years). STUDY
      APPRAISAL AND SYNTHESIS METHODS: Articles were grouped by study design: cross
      sectional, acute/short term, non-randomized, and randomized trials. Considerable
      heterogeneity existed within study groups for several important study parameters,
      therefore a meta-analysis was considered inappropriate. Results were synthesized
      and presented by study design. RESULTS: No effect of physical activity, exercise
      or exercise training on energy intake was shown in 59% of cross-sectional studies
      (n = 17), 69% of acute (n = 40), 50% of short-term (n = 10), 92% of non
      randomized (n = 12) and 75% of randomized trials (n = 24). Ninety-four percent of
      acute, 57% of short-term, 100% of non-randomized and 74% of randomized trials
      found no effect of exercise on macronutrient intake. Forty-six percent of cross
      sectional trials found lower fat intake with increased physical activity.
      LIMITATIONS: The literature is limited by the lack of adequately powered trials
      of sufficient duration, which have prescribed and measured exercise energy
      expenditure, or employed adequate assessment methods for energy and macronutrient
      intake. CONCLUSIONS: We found no consistent evidence that increased physical
      activity or exercise effects energy or macronutrient intake.

PMID- 24454705
TI  - Dietary and flight energetic adaptations in a salivary gland transcriptome of an
      insectivorous bat.
AB  - We hypothesized that evolution of salivary gland secretory proteome has been
      important in adaptation to insectivory, the most common dietary strategy among
      Chiroptera. A submandibular salivary gland (SMG) transcriptome was sequenced for
      the little brown bat, Myotis lucifugus. The likely secretory proteome of 23 genes
      included seven (RETNLB, PSAP, CLU, APOE, LCN2, C3, CEL) related to M. lucifugus
      insectivorous diet and metabolism. Six of the secretory proteins probably are
      endocrine, whereas one (CEL) most likely is exocrine. The encoded proteins are
      associated with lipid hydrolysis, regulation of lipid metabolism, lipid
      transport, and insulin resistance. They are capable of processing exogenous
      lipids for flight metabolism while foraging. Salivary carboxyl ester lipase (CEL)
      is thought to hydrolyze insect lipophorins, which probably are absorbed across
      the gastric mucosa during feeding. The other six proteins are predicted either to
      maintain these lipids at high blood concentrations or to facilitate transport and
      uptake by flight muscles. Expression of these seven genes and coordinated
      secretion from a single organ is novel to this insectivorous bat, and apparently
      has evolved through instances of gene duplication, gene recruitment, and
      nucleotide selection. Four of the recruited genes are single-copy in the Myotis
      genome, whereas three have undergone duplication(s) with two of these genes
      exhibiting evolutionary 'bursts' of duplication resulting in multiple paralogs.
      Evidence for episodic directional selection was found for six of seven genes,
      reinforcing the conclusion that the recruited genes have important roles in
      adaptation to insectivory and the metabolic demands of flight. Intragenic
      frequencies of mobile- element-like sequences differed from frequencies in the
      whole M. lucifugus genome. Differences among recruited genes imply separate
      evolutionary trajectories and that adaptation was not a single, coordinated
      event. 

PMID- 24454706
TI  - Potential cost-effectiveness of a new infant tuberculosis vaccine in South Africa
      -implications for clinical trials: a decision analysis.
AB  - Novel tuberculosis vaccines are in varying stages of pre-clinical and clinical
      development. This study seeks to estimate the potential cost-effectiveness of a
      BCG booster vaccine, while accounting for costs of large-scale clinical trials,
      using the MVA85A vaccine as a case study for estimating potential costs. We
      conducted a decision analysis from the societal perspective, using a 10-year time
      frame and a 3% discount rate. We predicted active tuberculosis cases and
      tuberculosis-related costs for a hypothetical cohort of 960,763 South African
      newborns (total born in 2009). We compared neonatal vaccination with bacille
      Calmette-Guerin alone to vaccination with bacille Calmette-Guerin plus a booster
      vaccine at 4 months. We considered booster efficacy estimates ranging from 40% to
      70%, relative to bacille Calmette-Guerin alone. We accounted for the costs of
      Phase III clinical trials. The booster vaccine was assumed to prevent progression
      to active tuberculosis after childhood infection, with protection decreasing
      linearly over 10 years. Trial costs were prorated to South Africa's global share
      of bacille Calmette-Guerin vaccination. Vaccination with bacille Calmette-Guerin
      alone resulted in estimated tuberculosis-related costs of $89.91 million 2012
      USD, and 13,610 tuberculosis cases in the birth cohort, over the 10 years.
      Addition of the booster resulted in estimated cost savings of $7.69-$16.68
      million USD, and 2,800-4,160 cases averted, for assumed efficacy values ranging
      from 40%-70%. A booster tuberculosis vaccine in infancy may result in net
      societal cost savings as well as fewer active tuberculosis cases, even if
      efficacy is relatively modest and large scale Phase III studies are required. 

PMID- 24454707
TI  - The role of intestinal microbiota in development of irinotecan toxicity and in
      toxicity reduction through dietary fibres in rats.
AB  - CPT-11 is a drug used as chemotherapy for colorectal cancer. CPT-11 causes toxic
      side-effects in patients. CPT-11 toxicity has been attributed to the activity of
      intestinal microbiota, however, intestinal microbiota may also have protective
      effects in CP!-11 chemotherapy. This study aimed to elucidate mechanisms through
      which microbiota and dietary fibres could modify host health. Rats bearing a Ward
      colon carcinoma were treated with a two-cycle CPT-11/5-fluorouracil therapy
      recapitulating clinical therapy of colorectal cancer. Animals were fed with a
      semi-purified diet or a semi-purified diet was supplemented with non-digestible
      carbohydrates (isomalto-oligosaccharides, resistant starch, fructo
      oligosaccharides, or inulin) in 3 independent experiments. Changes in intestinal
      microbiota, bacteria translocating to mesenteric lymphnodes, cecal GUD activity,
      and cecal SCFA production, and the intestinal concentration of CPT-11 and its
      metabolites were analysed. Non-digestible carbohydrates significantly influenced
      feed intake, body weight and other indicators of animal health. The
      identification of translocating bacteria and their quantification in cecal
      microbiota indicated that overgrowth of the intestine by opportunistic pathogens
      was not a major contributor to CPT-11 toxicity. Remarkably, fecal GUD activity
      positively correlated to body weight and feed intake but negatively correlated to
      cecal SN-38 concentrations and IL1-beta. The reduction in CPT-11 toxicity by non
      digestible carbohydrates did not correlate to stimulation of specific bacterial
      taxa. However, cecal butyrate concentrations and feed intake were highly
      correlated. The protective role of intestinal butyrate production was
      substantiated by a positive correlation of the host expression of MCT1
      (monocarboxylate transporter 1) with body weight as well as a positive
      correlation of the abundance of bacterial butyryl-CoA gene with cecal butyrate
      concentrations. These correlations support the interpretation that the influence
      of dietary fibre on CPT-11 toxicity is partially mediated by an increased cecal
      production of butyrate. 

PMID- 24454708
TI  - Postoperative admission to a dedicated geriatric unit decreases mortality in
      elderly patients with hip fracture.
AB  - BACKGROUND: Elderly patients with hip fracture have a 5 to 8 fold increased risk
      of death during the months following surgery. We tested the hypothesis that early
      geriatric management of these patients focused on co-morbidities and
      rehabilitation improved long term mortality. METHODS AND FINDINGS: In a cohort
      study over a 6 year period, we compared patients aged >70 years with hip fracture
      admitted to orthopedic versus geriatric departments in a time series analysis
      corresponding to the creation of a dedicated geriatric unit. Co-morbidities were
      assessed using the Cumulative Illness Rating Scale (CIRS). Each cohort was
      compared to matched cohorts extracted from a national registry (n = 51,275) to
      validate the observed results. Main outcome measure was 6-month mortality. We
      included 131 patients in the orthopedic cohort and 203 in the geriatric cohort.
      Co-morbidities were more frequent in the geriatric cohort (median CIRS: 8 vs 5,
      P<0.001). In the geriatric cohort, the proportion of patients who never walked
      again decreased (6% versus 22%, P<0.001). At 6 months, re-admission (14% versus
      29%, P = 0.007) and mortality (15% versus 24%, P = 0.04) were decreased. When co
      morbidities were taken into account, the risk ratio of death at 6 months was
      reduced (0.43, 95%CI 0.25 to 0.73, P = 0.002). Using matched cohorts, the average
      treatment effects on the treated associated to early geriatric management
      indicated a reduction in hospital mortality (-63%; 95% CI: -92% to -6%, P =
      0.006). CONCLUSIONS: Early admission to a dedicated geriatric unit improved 6
      month mortality and morbidity in elderly patients with hip fracture.

PMID- 24454709
TI  - In vitro and in vivo evaluation of cysteine and site specific conjugated
      herceptin antibody-drug conjugates.
AB  - Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a
      cytotoxic drug selectively to antigen expressing cells. Several components of an
      ADC including the selection of the antibody, the linker, the cytotoxic drug
      payload and the site of attachment used to attach the drug to the antibody are
      critical to the activity and development of the ADC. The cytotoxic drugs or
      payloads used to make ADCs are typically conjugated to the antibody through
      cysteine or lysine residues. This results in ADCs that have a heterogeneous
      number of drugs per antibody. The number of drugs per antibody commonly referred
      to as the drug to antibody ratio (DAR), can vary between 0 and 8 drugs for a IgG1
      antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for
      binding to the antigen expressing cells. Antibodies with 8 drugs per antibody
      have reduced in vivo stability, which may contribute to non target related
      toxicities. In these studies we incorporated a non-natural amino acid, para
      acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We
      covalently attached a cytotoxic drug to these sites to form an ADC which contains
      two drugs per antibody. We report the results from the first direct preclinical
      comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine
      conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid
      anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology
      profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also
      demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain
      their in vitro potency and in vivo efficacy against Her2 expressing human tumor
      cell lines. Our data suggests that site specific non-natural amino acid ADCs may
      have a superior therapeutic window than cysteine conjugated ADCs. 

PMID- 24454710
TI  - Mice lacking NMDA receptors in parvalbumin neurons display normal depression
      related behavior and response to antidepressant action of NMDAR antagonists.
AB  - The underlying circuit imbalance in major depression remains unknown and current
      therapies remain inadequate for a large group of patients. Discovery of the rapid
      antidepressant effects of ketamine--an NMDA receptor (NMDAR) antagonist--has
      linked the glutamatergic system to depression. Interestingly, dysfunction in the
      inhibitory GABAergic system has also been proposed to underlie depression and
      deficits linked to GABAergic neurons have been found with human imaging and in
      post-mortem material from depressed patients. Parvalbumin-expressing (PV)
      GABAergic interneurons regulate local circuit function through perisomatic
      inhibition and their activity is NMDAR-dependent, providing a possible link
      between NMDAR and the inhibitory system in the antidepressant effect of ketamine.
      We have therefore investigated the role of the NMDAR-dependent activity of PV
      interneurons for the development of depression-like behavior as well as for the
      response to rapid antidepressant effects of NMDAR antagonists. We used mutant
      mice lacking NMDA neurotransmission specifically in PV neurons (PV-Cre+/NR1f/f)
      and analyzed depression-like behavior and anhedonia. To study the acute and
      sustained effects of a single NMDAR antagonist administration, we established a
      behavioral paradigm of repeated exposure to forced swimming test (FST). We did
      not observe altered behavioral responses in the repeated FST or in a sucrose
      preference test in mutant mice. In addition, the behavioral response to
      administration of NMDAR antagonists was not significantly altered in mutant PV
      Cre+/NR1f/f mice. Our results show that NMDA-dependent neurotransmission in PV
      neurons is not necessary to regulate depression-like behaviors, and in addition
      that NMDARs on PV neurons are not a direct target for the NMDAR-induced
      antidepressant effects of ketamine and MK801.

PMID- 24454711
TI  - Animal-borne imaging reveals novel insights into the foraging behaviors and Diel
      activity of a large-bodied apex predator, the American alligator (Alligator
      mississippiensis).
AB  - Large-bodied, top- and apex predators (e.g., crocodilians, sharks, wolves, killer
      whales) can exert strong top-down effects within ecological communities through
      their interactions with prey. Due to inherent difficulties while studying the
      behavior of these often dangerous predatory species, relatively little is known
      regarding their feeding behaviors and activity patterns, information that is
      essential to understanding their role in regulating food web dynamics and
      ecological processes. Here we use animal-borne imaging systems (Crittercam) to
      study the foraging behavior and activity patterns of a cryptic, large-bodied
      predator, the American alligator (Alligator mississippiensis) in two estuaries of
      coastal Florida, USA. Using retrieved video data we examine the variation in
      foraging behaviors and activity patterns due to abiotic factors. We found the
      frequency of prey-attacks (mean = 0.49 prey attacks/hour) as well as the
      probability of prey-capture success (mean = 0.52 per attack) were significantly
      affected by time of day. Alligators attempted to capture prey most frequently
      during the night. Probability of prey-capture success per attack was highest
      during morning hours and sequentially lower during day, night, and sunset,
      respectively. Position in the water column also significantly affected prey
      capture success, as individuals' experienced two-fold greater success when
      attacking prey while submerged. These estimates are the first for wild adult
      American alligators and one of the few examples for any crocodilian species
      worldwide. More broadly, these results reveal that our understandings of
      crocodilian foraging behaviors are biased due to previous studies containing
      limited observations of cryptic and nocturnal foraging interactions. Our results
      can be used to inform greater understanding regarding the top-down effects of
      American alligators in estuarine food webs. Additionally, our results highlight
      the importance and power of using animal-borne imaging when studying the behavior
      of elusive large-bodied, apex predators, as it provides critical insights into
      their trophic and behavioral interactions.

PMID- 24454712
TI  - Predicting coral species richness: the effect of input variables, diversity and
      scale.
AB  - Coral reefs are facing a biodiversity crisis due to increasing human impacts,
      consequently, one third of reef-building corals have an elevated risk of
      extinction. Logistic challenges prevent broad-scale species-level monitoring of
      hard corals; hence it has become critical that effective proxy indicators of
      species richness are established. This study tests how accurately three potential
      proxy indicators (generic richness on belt transects, generic richness on point
      intercept transects and percent live hard coral cover on point-intercept
      transects) predict coral species richness at three different locations and two
      analytical scales. Generic richness (measured on a belt transect) was found to be
      the most effective predictor variable, with significant positive linear
      relationships across locations and scales. Percent live hard coral cover
      consistently performed poorly as an indicator of coral species richness. This
      study advances the practical framework for optimizing coral reef monitoring
      programs and empirically demonstrates that generic richness offers an effective
      way to predict coral species richness with a moderate level of precision. While
      the accuracy of species richness estimates will decrease in communities dominated
      by species-rich genera (e.g. Acropora), generic richness provides a useful
      measure of phylogenetic diversity and incorporating this metric into monitoring
      programs will increase the likelihood that changes in coral species diversity can
      be detected. 

PMID- 24454713
TI  - Oxytocin receptor gene polymorphisms are associated with human directed social
      behavior in dogs (Canis familiaris).
AB  - The oxytocin system has a crucial role in human sociality; several results prove
      that polymorphisms of the oxytocin receptor gene are related to complex social
      behaviors in humans. Dogs' parallel evolution with humans and their adaptation to
      the human environment has made them a useful species to model human social
      interactions. Previous research indicates that dogs are eligible models for
      behavioral genetic research, as well. Based on these previous findings, our
      research investigated associations between human directed social behaviors and
      two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide
      polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin
      receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs.
      Dogs' behavior traits have been estimated in a newly developed test series
      consisting of five episodes: Greeting by a stranger, Separation from the owner,
      Problem solving, Threatening approach, Hiding of the owner. Buccal samples were
      collected and DNA was isolated using standard protocols. SNPs in the 3' and 5'
      UTR regions were analyzed by polymerase chain reaction based techniques followed
      by subsequent electrophoresis analysis. The gene-behavior association analysis
      suggests that oxytocin receptor gene polymorphisms have an impact in both breeds
      on (i) proximity seeking towards an unfamiliar person, as well as their owner,
      and on (ii) how friendly dogs behave towards strangers, although the mediating
      molecular regulatory mechanisms are yet unknown. Based on these results, we
      conclude that similarly to humans, the social behavior of dogs towards humans is
      influenced by the oxytocin system.

PMID- 24454714
TI  - Age-dependent association among Helicobacter pylori infection, serum pepsinogen
      levels and immune response of children to live oral cholera vaccine CVD 103-HgR.
AB  - BACKGROUND: Through its effects on gastric secretion, we hypothesized that
      Helicobacter pylori infection may influence oral immunization. Accordingly, we
      examined the association between H. pylori infection, serum pepsinogen (PG)
      (measures for H. pylori gastritis) and vibriocidal antibody (a correlate of
      protection) seroconversion following oral immunization with CVD 103-HgR live
      cholera vaccine among children of different ages. METHODS: Sera from 422 Chilean
      children who were vaccinated with a single dose of CVD 103-HgR were tested by
      ELISA for serum IgG antibodies to H. pylori, PG I and PG II levels and antibodies
      to Shigella flexneri 2a lipopolysaccharide and hepatitis A virus (as markers of
      low socioeconomic status and exposure to enteric pathogens). RESULTS: The
      likelihood of vibriocidal antibody seroconversion following vaccination with CVD
      103-HgR was significantly decreased in H. pylori-seropositive children age 6
      months to 4 years with PG II>8 ug/L (adjusted OR 0.14 (95% CI 0.03-0.61; P =
      0.009), and also in H. pylori seropositives with lower PG II level (adjusted OR
      0.34, 95% CI 0.14-0.83; P = 0.017), compared to H. pylori-seronegatives. H.
      pylori-seropositive children aged 5-9 years with serum PG I>30 ug/L (indicating
      more severe gastritis) had higher odds of vibriocidal seroconversion than those
      with lower PG I levels (adjusted OR 4.41, 95%CI 1.26-15.38; P = 0.02). There was
      no significant association between exposures to S. flexneri 2a or hepatitis A
      virus and vibriocidal seroconversion. CONCLUSIONS: As H. pylori gastritis
      progresses with increasing pediatric age in developing country venues, changes in
      gastric secretion ensue that we believe explain the observed differences in age
      related immune responses to immunization with live oral cholera vaccine. The
      effect of H. pylori and changes of gastric acid secretion on the immunogenicity
      of various oral vaccines should be studied in different developing, transitional
      and industrialized country settings.

PMID- 24454715
TI  - The value of T2* in differentiating metastatic from benign axillary lymph nodes
      in patients with breast cancer--a preliminary in vivo study.
AB  - BACKGROUND: Accurate detection and determination of axillary lymph node
      metastasis are crucial for the clinical management of patients with breast
      cancer. Noninvasive imaging methods including ultrasound (US), computed
      tomography (CT), or conventional magnetic resonance imaging (MRI) are not yet
      accurate enough. The purpose of this study was to investigate the value of in
      vivo T2* in differentiating metastatic from benign axillary lymph nodes in
      patients with breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this
      institutional review board approved study, 35 women with breast cancer underwent
      multi-echo T2* weighted imaging (T2*WI) of the axillary area on a 3.0 T clinical
      magnetic resonance (MR) imaging system. T2* values of pathologically proven
      benign and metastatic axillary lymph nodes were calculated and compared. Receiver
      operating characteristics (ROC) analysis was conducted to evaluate the diagnostic
      ability. The areas under the ROC curve (AUCs) and the confidence intervals (CIs)
      were assessed. In total, 56 metastatic and 65 benign axillary lymph nodes were
      identified in this study. For metastatic lymph nodes, the average T2* value
      (55.96+/-11.87 ms) was significantly longer than that of the benign lymph nodes
      (26.00+/-5.51 ms, P<0.05). The AUC of T2* in differentiating benign from
      metastatic lymph nodes was 0.993. The cut-off value of 37.5 milliseconds (ms)
      gave a sensitivity of 94.6%, a specificity of 98.5%, a positive predictive value
      of 98.17 and a negative predictive value 95.54. CONCLUSIONS: In vivo T2* can
      differentiate benign from metastatic axillary lymph nodes in patients with breast
      cancer. The high sensitivity and specificity as well as the easiness suggest its
      high potential for use in clinical practice.

PMID- 24454716
TI  - Relationship between changes in body fat and a decline of renal function in the
      elderly.
AB  - Obesity is a risk factor for chronic kidney disease, and its prevalence among the
      elderly is increasing. We investigated the effects of changes in body fat
      percentage (BFP) on the longitudinal changes in the estimated glomerular
      filtration rate (eGFR) in the elderly. This prospective cohort study included 390
      participants aged >65 years who underwent bioelectrical impedance analysis at
      baseline and follow-up as a part of the Korean Longitudinal Study on Health and
      Aging. After a median follow-up period of 5.3 years, BFP was significantly higher
      than that at the start point (P<0.05). Participants who had the largest increase
      in BFP had the highest BMI and waist circumference (WC) (P<0.001). The highest
      tertile had the highest white blood cell count and erythrocyte sedimentation
      rate, incidence of rapid progression, and decline in eGFR >25% (P<=0.017, P =
      0.025, P = 0.005, respectively). The lowest tertile had the lowest triglyceride
      and highest high-density lipoprotein levels (P<0.05). The adjusted decline rate
      in eGFR was correlated with a change in BFP (P = 0.039), but not with that in BMI
      or WC. The highest tertile had a 4.875-fold increase in the risk for rapid
      progression to a decline in eGFR (95% CI: 1.366-17.397) and a 4.931-fold decrease
      in the risk to a decline in eGFR>25% (95% CI: 1.617-15.037), when compared with
      the lowest tertile. In subgroup analysis, the incidence of renal outcomes was
      significantly increased according to the increase in BFP in patients with lower
      eGFR (P<=0.010). A change in BFP may be associated with inflammation and
      dyslipidemia development, and longitudinal changes in body fat are related to a
      decrease in eGFR in the elderly. 

PMID- 24454717
TI  - Performance of single and concatenated sets of mitochondrial genes at inferring
      metazoan relationships relative to full mitogenome data.
AB  - Mitochondrial (mt) genes are some of the most popular and widely-utilized genetic
      loci in phylogenetic studies of metazoan taxa. However, their linked nature has
      raised questions on whether using the entire mitogenome for phylogenetics is
      overkill (at best) or pseudoreplication (at worst). Moreover, no studies have
      addressed the comparative phylogenetic utility of mitochondrial genes across
      individual lineages within the entire Metazoa. To comment on the phylogenetic
      utility of individual mt genes as well as concatenated subsets of genes, we
      analyzed mitogenomic data from 1865 metazoan taxa in 372 separate lineages
      spanning genera to subphyla. Specifically, phylogenies inferred from these
      datasets were statistically compared to ones generated from all 13 mt protein
      coding (PC) genes (i.e., the "supergene" set) to determine which single genes
      performed "best" at, and the minimum number of genes required to, recover the
      "supergene" topology. Surprisingly, the popular marker COX1 performed poorest,
      while ND5, ND4, and ND2 were most likely to reproduce the "supergene" topology.
      Averaged across all lineages, the longest ~2 mt PC genes were sufficient to
      recreate the "supergene" topology, although this average increased to ~5 genes
      for datasets with 40 or more taxa. Furthermore, concatenation of the three "best"
      performing mt PC genes outperformed that of the three longest mt PC genes (i.e,
      ND5, COX1, and ND4). Taken together, while not all mt PC genes are equally
      interchangeable in phylogenetic studies of the metazoans, some subset can serve
      as a proxy for the 13 mt PC genes. However, the exact number and identity of
      these genes is specific to the lineage in question and cannot be applied
      indiscriminately across the Metazoa. 

PMID- 24454718
TI  - Fostering maternal and newborn care in India the Yashoda way: does this improve
      maternal and newborn care practices during institutional delivery?
AB  - BACKGROUND: The Yashoda program, named after a legendary foster-mother in Indian
      mythology, under the Norway-India Partnership Initiative was launched as a pilot
      program in 2008 to improve the quality of maternal and neonatal care at
      facilities in select districts of India. Yashodas were placed mainly at district
      hospitals, which are high delivery load facilities, to provide support and care
      to mothers and newborns during their stay at these facilities. This study
      presents the results from the evaluation of this intervention in two states in
      India. METHODS: Data collection methods included in-depth interviews with
      healthcare providers and mothers and a survey of mothers who had recently
      delivered within a quasi-experimental design. Fifty IDIs were done and 1,652
      mothers who had delivered in the past three months were surveyed during 2010 and
      2011. RESULTS: A significantly higher proportion of mothers at facilities with
      Yashodas (55 percent to 97 percent) received counseling on immunization,
      breastfeeding, family planning, danger signs, and nutrition compared to those in
      control districts (34 percent to 66 percent). Mothers in intervention facilities
      were four to five times more likely to receive postnatal checks than mothers in
      control facilities. Among mothers who underwent cesarean sections, initiation of
      breastfeeding within five hours was 50 percent higher in intervention facilities.
      Mothers and families also reported increased support, care and respect at
      intervention facilities. CONCLUSION: Yashoda as mothers' aide thus seems to be an
      effective intervention to improve quality of maternal and newborn care in India.
      Scaling up of this intervention is recommended in district hospitals and other
      facilities with high volume of deliveries.

PMID- 24454719
TI  - Lifespan and aggregate size variables in specifications of mortality or
      survivorship.
AB  - A specification of mortality or survivorship provides respective explicit details
      about mortality's or survivorship's relationships with one or more other
      variables (e.g., age, sex, etc.). Previous studies have discovered and analyzed
      diverse specifications of mortality or survivorship; these discoveries and
      analyses suggest that additional specifications of mortality or survivorship have
      yet to be discovered and analyzed. In consistency with previous research,
      multivariable limited powered polynomials regression analyses of mortality and
      survivorship of selected humans (Swedes, 1760-2008) and selected insects (caged
      medflies) show age-specific, historical-time-specific, environmental-context
      specific, and sex-specific mortality and survivorship. These analyses also
      present discoveries of hitherto unknown lifespan-specific, contemporary-aggregate
      size-specific, and lifespan-aggregate-size-specific mortality and survivorship.
      The results of this investigation and results of previous research help identify
      variables for inclusion in regression models of mortality or survivorship.
      Moreover, these results and results of previous research strengthen the
      suggestion that additional specifications of mortality or survivorship have yet
      to be discovered and analyzed, and they also suggest that specifications of
      mortality and survivorship indicate corresponding specifications of frailty and
      vitality. Furthermore, the present analyses reveal the usefulness of a
      multivariable limited powered polynomials regression model-building approach.
      This article shows that much has yet to be learned about specifications of
      mortality or survivorship of diverse kinds of individuals in diverse times and
      places. 

PMID- 24454720
TI  - XRCC3 C18067T polymorphism contributes a decreased risk to both basal cell
      carcinoma and squamous cell carcinoma: evidence from a meta-analysis.
AB  - BACKGROUND: The X-ray repair cross-complementing group 3 (XRCC3) in homologous
      recombination repair (HRR) pathway plays a very important role in DNA double
      strand break repair (DSBR). Variations in the XRCC3 gene might lead to altered
      protein structure or function which may change DSBR efficiency and result in
      cancer. The XRCC3 C18067T polymorphism has been reported to be associated with
      skin cancer susceptibility, yet the results of these previous results have been
      inconsistent or controversial. To derive a more precise estimation of the
      association, we conducted a meta-analysis. METHODS: The quality of the studies
      was assessed according to a predefined scale. The association between the XRCC3
      C18067T polymorphism and skin cancer risk was assessed by odds ratios (ORs)
      together with their 95% confidence intervals (CIs). RESULTS: Overall, no
      significant association was observed between XRCC3 C18067T polymorphism and skin
      cancer risk in any genetic model. Stratified analyses according to tumor type,
      significant association was found in the relationship between XRCC3 C18067T
      polymorphism and nonmelanoma skin cancer risk (homozygote comparison TT versus
      CC: OR = 0.74, 95%CI = 0.61-0.90, P = 0.003; recessive model TT versus TC/CC: OR
      = 0.81, 95%CI = 0.68-0.95, P = 0.01). Furthermore, significant association was
      also observed in XRCC3 C18067T polymorphism with both basal cell carcinoma risk
      (homozygote comparison TT versus CC: OR = 0.70, 95%CI = 0.53-0.92, P = 0.011;
      recessive model TT versus. TC/CC: OR = 0.74, 95%CI = 0.60-0.92, P = 0.007) and
      squamous cell carcinoma risk (heterozygote comparison TT versus .CC: OR = 0.81,
      95%CI = 0.67-0.99, P = 0.04; dominant model TT/TC versus .CC: OR = 0.81, 95%CI =
      0.68-0.98, P = 0.029). CONCLUSION: The present meta-analysis demonstrates that
      XRCC3 C18067T polymorphism was not associated with risk of cutaneous melanoma but
      contributed a decreased risk to both basal cell carcinoma and squamous cell
      carcinoma.

PMID- 24454722
TI  - An integrated approach is needed for ecosystem based fisheries management:
      insights from ecosystem-level management strategy evaluation.
AB  - An ecosystem approach is widely seen as a desirable goal for fisheries management
      but there is little consensus on what strategies or measures are needed to
      achieve it. Management strategy evaluation (MSE) is a tool that has been widely
      used to develop and test single species fisheries management strategies and is
      now being extended to support ecosystem based fisheries management (EBFM). We
      describe the application of MSE to investigate alternative strategies for
      achieving EBFM goals for a complex multispecies fishery in southeastern
      Australia. The study was undertaken as part of a stakeholder driven process to
      review and improve the ecological, economic and social performance of the
      fishery. An integrated management strategy, involving combinations of measures
      including quotas, gear controls and spatial management, performed best against a
      wide range of objectives and this strategy was subsequently adopted in the
      fishery, leading to marked improvements in performance. Although particular to
      one fishery, the conclusion that an integrated package of measures outperforms
      single focus measures we argue is likely to apply widely in fisheries that aim to
      achieve EBFM goals. 

PMID- 24454721
TI  - Patient and healthcare provider barriers to hypertension awareness, treatment and
      follow up: a systematic review and meta-analysis of qualitative and quantitative
      studies.
AB  - BACKGROUND: Although the importance of detecting, treating, and controlling
      hypertension has been recognized for decades, the majority of patients with
      hypertension remain uncontrolled. The path from evidence to practice contains
      many potential barriers, but their role has not been reviewed systematically.
      This review aimed to synthesize and identify important barriers to hypertension
      control as reported by patients and healthcare providers. METHODS: Electronic
      databases MEDLINE, EMBASE and Global Health were searched systematically up to
      February 2013. Two reviewers independently selected eligible studies. Two
      reviewers categorized barriers based on a theoretical framework of behavior
      change. The theoretical framework suggests that a change in behavior requires a
      strong commitment to change [intention], the necessary skills and abilities to
      adopt the behavior [capability], and an absence of health system and support
      constraints. FINDINGS: Twenty-five qualitative studies and 44 quantitative
      studies met the inclusion criteria. In qualitative studies, health system
      barriers were most commonly discussed in studies of patients and health care
      providers. Quantitative studies identified disagreement with clinical
      recommendations as the most common barrier among health care providers.
      Quantitative studies of patients yielded different results: lack of knowledge was
      the most common barrier to hypertension awareness. Stress, anxiety and depression
      were most commonly reported as barriers that hindered or delayed adoption of a
      healthier lifestyle. In terms of hypertension treatment adherence, patients
      mostly reported forgetting to take their medication. Finally, priority setting
      barriers were most commonly reported by patients in terms of following up with
      their health care providers. CONCLUSIONS: This review identified a wide range of
      barriers facing patients and health care providers pursuing hypertension control,
      indicating the need for targeted multi-faceted interventions. More
      methodologically rigorous studies that encompass the range of barriers and that
      include low- and middle-income countries are required in order to inform policies
      to improve hypertension control.

PMID- 24454723
TI  - Factors influencing obstacle crossing performance in patients with Parkinson's
      disease.
AB  - BACKGROUND: Tripping over obstacles is the major cause of falls in community
      dwelling patients with Parkinson's disease (PD). Understanding the factors
      associated with the obstacle crossing behavior may help to develop possible
      training programs for crossing performance. This study aimed to identify the
      relationships and important factors determining obstacle crossing performance in
      patients with PD. METHODS: Forty-two idiopathic patients with PD (Hoehn and Yahr
      stages I to III) participated in this study. Obstacle crossing performance was
      recorded by the Liberty system, a three-dimensional motion capture device.
      Maximal isometric strength of the lower extremity was measured by a handheld
      dynamometer. Dynamic balance and sensory integration ability were assessed using
      the Balance Master system. Movement velocity (MV), maximal excursion (ME), and
      directional control (DC) were obtained during the limits of stability test to
      quantify dynamic balance. The sum of sensory organization test (SOT) scores was
      used to quantify sensory organization ability. RESULTS: Both crossing stride
      length and stride velocity correlated significantly with lower extremity muscle
      strength, dynamic balance control (forward and sideward), and sum of SOT scores.
      From the regression model, forward DC and ankle dorsiflexor strength were
      identified as two major determinants for crossing performance (R(2) = .37 to.41
      for the crossing stride length, R(2) = .43 to.44 for the crossing stride
      velocity). CONCLUSIONS: Lower extremity muscle strength, dynamic balance control
      and sensory integration ability significantly influence obstacle crossing
      performance. We suggest an emphasis on muscle strengthening exercises (especially
      ankle dorsiflexors), balance training (especially forward DC), and sensory
      integration training to improve obstacle crossing performance in patients with
      PD.

PMID- 24454724
TI  - Specific disruption of hippocampal mossy fiber synapses in a mouse model of
      familial Alzheimer's disease.
AB  - The earliest stages of Alzheimer's disease (AD) are characterized by deficits in
      memory and cognition indicating hippocampal pathology. While it is now recognized
      that synapse dysfunction precedes the hallmark pathological findings of AD, it is
      unclear if specific hippocampal synapses are particularly vulnerable. Since the
      mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies
      critical functions disrupted in AD, we utilized serial block-face electron
      microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial
      Alzheimer's disease (FAD). FAD mutant MF terminal complexes were severely
      disrupted compared to control - they were smaller, contacted fewer postsynaptic
      spines and had greater numbers of presynaptic filopodial processes. Multi-headed
      CA3 dendritic spines in the FAD mutant condition were reduced in complexity and
      had significantly smaller sites of synaptic contact. Significantly, there was no
      change in the volume of classical dendritic spines at neighboring inputs to CA3
      neurons suggesting input-specific defects in the early course of AD related
      pathology. These data indicate a specific vulnerability of the DG-CA3 network in
      AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific
      alterations in mouse models of human disease. 

PMID- 24454725
TI  - Early life history of Alatina cf. moseri populations from Australia and Hawaii
      with implications for taxonomy (Cubozoa: Carybdeida, Alatinidae).
AB  - The early life stages of the cubomedusa Alatina cf. moseri from Osprey Reef
      (North Queensland, Australia) and Waikiki (Oahu, Hawaii) were studied using
      laboratory-based culturing conditions. Spawning populations from both regions
      were observed with reliable periodicity allowing polyp cultures from these
      locations to be collected and established under laboratory conditions. The polyps
      of this species were successfully reared from spawning adults. Polyps of Alatina
      cf. moseri were cultured at temperatures of 23-28  degrees C, developed up to 19
      tentacles and reached up to 1.70 mm in height. The balloon-shaped hypostomes
      possessed 4 well-defined lips. The polyps increased their numbers by means of
      formation of either sedentary polyp buds or creeping-polyp buds, which attached
      after 2-3 days. Metamorphosis occurred at temperatures of 25-28  degrees C.
      Development of polyps and medusae were achieved for the first time within the
      genus Alatina and allowed comparisons of early life history between these and
      other species of the Carybdeida families. The metamorphosis and young medusa of
      this genus showed characters that differed distinctly from those noted for other
      Carybdeida species, but are very similar to the one described from Puerto Rico by
      Arneson and Cutress in 1976 for Alatina sp. (named by them Carybdea alata). Based
      on this evidence, the discrepancies in original specimen descriptions and the
      previous genetic comparisons, we support the suggestion that the two previously
      described species of Alatina from Australia and Hawaii (Alatina mordens and
      Alatina moseri) appear to represent artificial taxonomic units and may in fact be
      the same as the original Carybdea alata species named from Puerto Rico. Further
      taxonomic studies are desperately needed in order to clarify the various species
      and description discrepancies that exist within this newly proposed genus.

PMID- 24454726
TI  - Gastroprotective and ulcer healing effects of essential oil of Hyptis martiusii
      Benth. (Lamiaceae).
AB  - Hyptis martiusii Benth. is an aromatic plant found in abundance in northeastern
      Brazil that is used in ethnomedicine to treat gastric disorders. The aim of this
      study was to elucidate the mechanisms of action involved in the gastroprotection
      of the essential oil of Hyptis martiusii (EOHM) and to evaluate its healing
      capacity. Wistar rats were exposed to different protocols and subsequently were
      treated with 1% Tween-80 aqueous solution (negative control), pantoprazole,
      carbenoxolone, N-acetylcysteine (depending on the specificity of each model) or
      EOHM. The antisecretory activity (basal or stimulated) was determined using the
      pyloric ligature method. The gastroprotective action of nitric oxide and
      sulphydryl groups (-SH groups), as well as the quantification of adherent mucus
      and the levels of malondialdehyde and -SH groups in gastric mucosa, were
      evaluated using ethanol-induced gastric ulcer model. The healing ability was
      evaluated using the acetic acid-induced gastric ulcer model and histological and
      immunohistochemical analysis (HE, PAS and PCNA). EOHM (400 mg/kg) reduced the
      volume and acidity of gastric secretion stimulated by histamine and pentagastrin.
      The gastroprotective effect of EOHM involves the participation of endogenous
      sulfhydryl groups. EOHM increased mucus production (54.8%), reduced levels of MDA
      (72.5%) and prevented the depletion of -SH groups (73.8%) in the gastric mucosa.
      The treatment with EOHM reduced in 70.3% the gastric lesion area, promoting
      significant regeneration of the gastric mucosa, as confirmed by histological
      analysis and analysis of proliferating cell nuclear antigen. The results show
      that gastroprotective effect of EOHM is mediated by cytoprotective and
      antioxidant mechanisms and by their antisecretory activity, and suggest that the
      essential oil of Hyptis martiusii is a promising candidate for the treatment of
      gastric ulcers. 

PMID- 24454727
TI  - Detecting unidentified changes.
AB  - Does becoming aware of a change to a purely visual stimulus necessarily cause the
      observer to be able to identify or localise the change or can change detection
      occur in the absence of identification or localisation? Several theories of
      visual awareness stress that we are aware of more than just the few objects to
      which we attend. In particular, it is clear that to some extent we are also aware
      of the global properties of the scene, such as the mean luminance or the
      distribution of spatial frequencies. It follows that we may be able to detect a
      change to a visual scene by detecting a change to one or more of these global
      properties. However, detecting a change to global property may not supply us with
      enough information to accurately identify or localise which object in the scene
      has been changed. Thus, it may be possible to reliably detect the occurrence of
      changes without being able to identify or localise what has changed. Previous
      attempts to show that this can occur with natural images have produced mixed
      results. Here we use a novel analysis technique to provide additional evidence
      that changes can be detected in natural images without also being identified or
      localised. It is likely that this occurs by the observers monitoring the global
      properties of the scene. 

PMID- 24454728
TI  - HPTN 071 (PopART): a cluster-randomized trial of the population impact of an HIV
      combination prevention intervention including universal testing and treatment:
      mathematical model.
AB  - BACKGROUND: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can
      nearly eliminate HIV transmission from successfully treated HIV-infected
      individuals within couples. Here, we present the mathematical modeling used to
      inform the design and monitoring of a new trial aiming to test whether widespread
      provision of ART is feasible and can substantially reduce population-level HIV
      incidence. METHODS AND FINDINGS: The HPTN 071 (PopART) trial is a three-arm
      cluster-randomized trial of 21 large population clusters in Zambia and South
      Africa, starting in 2013. A combination prevention package including home-based
      voluntary testing and counseling, and ART for HIV positive individuals, will be
      delivered in arms A and B, with ART offered universally in arm A and according to
      national guidelines in arm B. Arm C will be the control arm. The primary endpoint
      is the cumulative three-year HIV incidence. We developed a mathematical model of
      heterosexual HIV transmission, informed by recent data on HIV-1 natural history.
      We focused on realistically modeling the intervention package. Parameters were
      calibrated to data previously collected in these communities and national
      surveillance data. We predict that, if targets are reached, HIV incidence over
      three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The
      considerable uncertainty in the predicted reduction in incidence justifies the
      need for a trial. The main drivers of this uncertainty are possible community
      level behavioral changes associated with the intervention, uptake of testing and
      treatment, as well as ART retention and adherence. CONCLUSIONS: The HPTN 071
      (PopART) trial intervention could reduce HIV population-level incidence by >60%
      over three years. This intervention could serve as a paradigm for national or
      supra-national implementation. Our analysis highlights the role mathematical
      modeling can play in trial development and monitoring, and more widely in
      evaluating the impact of treatment as prevention.

PMID- 24454729
TI  - Sloth hair as a novel source of fungi with potent anti-parasitic, anti-cancer and
      anti-bacterial bioactivity.
AB  - The extraordinary biological diversity of tropical forests harbors a rich
      chemical diversity with enormous potential as a source of novel bioactive
      compounds. Of particular interest are new environments for microbial discovery.
      Sloths--arboreal mammals commonly found in the lowland forests of Panama--carry a
      wide variety of micro- and macro-organisms on their coarse outer hair. Here we
      report for the first time the isolation of diverse and bioactive strains of fungi
      from sloth hair, and their taxonomic placement. Eighty-four isolates of fungi
      were obtained in culture from the surface of hair that was collected from living
      three-toed sloths (Bradypus variegatus, Bradypodidae) in Soberania National Park,
      Republic of Panama. Phylogenetic analyses revealed a diverse group of Ascomycota
      belonging to 28 distinct operational taxonomic units (OTUs), several of which are
      divergent from previously known taxa. Seventy-four isolates were cultivated in
      liquid broth and crude extracts were tested for bioactivity in vitro. We found a
      broad range of activities against strains of the parasites that cause malaria
      (Plasmodium falciparum) and Chagas disease (Trypanosoma cruzi), and against the
      human breast cancer cell line MCF-7. Fifty fungal extracts were tested for
      antibacterial activity in a new antibiotic profile screen called BioMAP; of
      these, 20 were active against at least one bacterial strain, and one had an
      unusual pattern of bioactivity against Gram-negative bacteria that suggests a
      potentially new mode of action. Together our results reveal the importance of
      exploring novel environments for bioactive fungi, and demonstrate for the first
      time the taxonomic composition and bioactivity of fungi from sloth hair.

PMID- 24454730
TI  - Caveolin-1 is up-regulated by GLI1 and contributes to GLI1-driven EMT in
      hepatocellular carcinoma.
AB  - Caveolin-1 (Cav-1) has been recently identified to be over-expressed in
      hepatocellular carcinoma (HCC) and promote HCC cell motility and invasion ability
      via inducing epithelial-mesenchymal transition (EMT). However, the mechanism of
      aberrant overexpression of Cav-1 remains vague. Here, we observed that Cav-1
      expression was positively associated with GLI1 expression in HCC tissues. Forced
      expression of GLI1 up-regulated Cav-1 in Huh7 cells, while knockdown of GLI1
      decreased expression of Cav-1 in SNU449 cells. Additionally, silencing Cav-1
      abolished GLI1-induced EMT of Huh7 cells. The correlation between GLI1 and Cav-1
      was confirmed in tumor specimens from HCC patients and Cav-1 was found to be
      associated with poor prognosis after hepatic resection. The relationship between
      protein expression of GLI1 and Cav-1 was also established in HCC xenografts of
      nude mice. These results suggest that GLI1 may be attributed to Cav-1 up
      regulation which plays an important role in GLI1-driven EMT phenotype in HCC. 

PMID- 24454731
TI  - Where does N(epsilon)-trimethyllysine for the carnitine biosynthesis in mammals
      come from?
AB  - N(epsilon)-trimethyllysine (TML) is a non-protein amino acid which takes part in
      the biosynthesis of carnitine. In mammals, the breakdown of endogenous proteins
      containing TML residues is recognized as starting point for the carnitine
      biosynthesis. Here, we document that one of the main sources of TML could be the
      vegetables which represent an important part of daily alimentation for most
      mammals. A HPLC-ESI-MS/MS method, which we previously developed for the analysis
      of N(G)-methylarginines, was utilized to quantitate TML in numerous vegetables.
      We report that TML, believed to be rather rare in plants as free amino acid, is,
      instead, ubiquitous in them and at not negligible levels. The occurrence of TML
      has been also confirmed in some vegetables by a HPLC method with fluorescence
      detection. Our results establish that TML can be introduced as free amino acid in
      conspicuous amounts from vegetables. The current opinion is that mammals utilize
      the breakdown of their endogenous proteins containing TML residues as starting
      point for carnitine biosynthesis. However, our finding raises the question of
      whether a tortuous and energy expensive route as the one of TML formation from
      the breakdown of endogenous proteins is really preferred when the substance is so
      easily available in vegetable foods. On the basis of this result, it must be
      taken into account that in mammals TML might be mainly introduced by diet.
      However, when the alimentary intake becomes insufficient, as during starvation,
      it might be supplied by endogenous protein breakdown. 

PMID- 24454732
TI  - MicroRNA-147 induces a mesenchymal-to-epithelial transition (MET) and reverses
      EGFR inhibitor resistance.
AB  - BACKGROUND: The epithelial-mesenchymal transition (EMT) is a key developmental
      program that is often activated during cancer progression and may promote
      resistance to therapy. An analysis of patients (n = 71) profiled with both gene
      expression and a global microRNA assessment (~ 415 miRs) identified miR-147 as
      highly anti-correlated with an EMT gene expression signature score and postulated
      to reverse EMT (MET). METHODS AND FINDINGS: miR-147 was transfected into colon
      cancer cells (HCT116, SW480) as well as lung cancer cells (A-549). The cells were
      assessed for morphological changes, and evaluated for effects on invasion,
      motility, and the expression of key EMT markers. Resistance to chemotherapy was
      evaluated by treating cells with gefitinib, an EGFR inhibitor. The downstream
      genes regulated by miR-147 were assayed using the Affymetrix GeneChip U133
      Plus2.0 platform. miR-147 was identified to: 1. cause MET primarily by increasing
      the expression of CDH1 and decreasing that of ZEB1; 2. inhibit the invasion and
      motility of cells; 3. cause G1 arrest by up-regulating p27 and down-regulating
      cyclin D1. miR-147 also dramatically reversed the native drug resistance of the
      colon cancer cell line HCT116 to gefitinib. miR-147 significantly repressed Akt
      phosphorylation, and knockdown of Akt with siRNA induced MET. The morphologic
      effects of miR-147 on cells appear to be attenuated by TGF-B1, promoting a
      plastic and reversible transition between MET and EMT. CONCLUSION: miR-147
      induced cancer cells to undergo MET and induced cell cycle arrest, suggesting a
      potential tumor suppressor role. miR-147 strikingly increased the sensitivity to
      EGFR inhibitor, gefitinib in cell with native resistance. We conclude that miR
      147 might have therapeutic potential given its ability to inhibit proliferation,
      induce MET, as well as reverse drug sensitivity.

PMID- 24454733
TI  - Deriving a mutation index of carcinogenicity using protein structure and protein
      interfaces.
AB  - With the advent of Next Generation Sequencing the identification of mutations in
      the genomes of healthy and diseased tissues has become commonplace. While much
      progress has been made to elucidate the aetiology of disease processes in cancer,
      the contributions to disease that many individual mutations make remain to be
      characterised and their downstream consequences on cancer phenotypes remain to be
      understood. Missense mutations commonly occur in cancers and their consequences
      remain challenging to predict. However, this knowledge is becoming more vital,
      for both assessing disease progression and for stratifying drug treatment
      regimes. Coupled with structural data, comprehensive genomic databases of
      mutations such as the 1000 Genomes project and COSMIC give an opportunity to
      investigate general principles of how cancer mutations disrupt proteins and their
      interactions at the molecular and network level. We describe a comprehensive
      comparison of cancer and neutral missense mutations; by combining features
      derived from structural and interface properties we have developed a
      carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with
      other methods, we observe that InCa can predict mutations that might not be
      detected by other methods. We also discuss general limitations shared by all
      predictors that attempt to predict driver mutations and discuss how this could
      impact high-throughput predictions. A web interface to a server implementation is
      publicly available at http://inca.icr.ac.uk/. 

PMID- 24454734
TI  - Biological motion coding in the brain: analysis of visually driven EEG functional
      networks.
AB  - Herein, we address the time evolution of brain functional networks computed from
      electroencephalographic activity driven by visual stimuli. We describe how these
      functional network signatures change in fast scale when confronted with point
      light display stimuli depicting biological motion (BM) as opposed to scrambled
      motion (SM). Whereas global network measures (average path length, average
      clustering coefficient, and average betweenness) computed as a function of time
      did not discriminate between BM and SM, local node properties did. Comparing the
      network local measures of the BM condition with those of the SM condition, we
      found higher degree and betweenness values in the left frontal (F7) electrode, as
      well as a higher clustering coefficient in the right occipital (O2) electrode,
      for the SM condition. Conversely, for the BM condition, we found higher degree
      values in central parietal (Pz) electrode and a higher clustering coefficient in
      the left parietal (P3) electrode. These results are discussed in the context of
      the brain networks involved in encoding BM versus SM. 

PMID- 24454735
TI  - Emergence of connectivity motifs in networks of model neurons with short- and
      long-term plastic synapses.
AB  - Recent experimental data from the rodent cerebral cortex and olfactory bulb
      indicate that specific connectivity motifs are correlated with short-term
      dynamics of excitatory synaptic transmission. It was observed that neurons with
      short-term facilitating synapses form predominantly reciprocal pairwise
      connections, while neurons with short-term depressing synapses form predominantly
      unidirectional pairwise connections. The cause of these structural differences in
      excitatory synaptic microcircuits is unknown. We show that these connectivity
      motifs emerge in networks of model neurons, from the interactions between short
      term synaptic dynamics (SD) and long-term spike-timing dependent plasticity
      (STDP). While the impact of STDP on SD was shown in simultaneous neuronal pair
      recordings in vitro, the mutual interactions between STDP and SD in large
      networks are still the subject of intense research. Our approach combines an SD
      phenomenological model with an STDP model that faithfully captures long-term
      plasticity dependence on both spike times and frequency. As a proof of concept,
      we first simulate and analyze recurrent networks of spiking neurons with random
      initial connection efficacies and where synapses are either all short-term
      facilitating or all depressing. For identical external inputs to the network, and
      as a direct consequence of internally generated activity, we find that networks
      with depressing synapses evolve unidirectional connectivity motifs, while
      networks with facilitating synapses evolve reciprocal connectivity motifs. We
      then show that the same results hold for heterogeneous networks, including both
      facilitating and depressing synapses. This does not contradict a recent theory
      that proposes that motifs are shaped by external inputs, but rather complements
      it by examining the role of both the external inputs and the internally generated
      network activity. Our study highlights the conditions under which SD-STDP might
      explain the correlation between facilitation and reciprocal connectivity motifs,
      as well as between depression and unidirectional motifs. 

PMID- 24454736
TI  - Bat airway epithelial cells: a novel tool for the study of zoonotic viruses.
AB  - Bats have been increasingly recognized as reservoir of important zoonotic
      viruses. However, until now many attempts to isolate bat-borne viruses in cell
      culture have been unsuccessful. Further, experimental studies on reservoir host
      species have been limited by the difficulty of rearing these species. The
      epithelium of the respiratory tract plays a central role during airborne
      transmission, as it is the first tissue encountered by viral particles. Although
      several cell lines from bats were established recently, no well-characterized,
      selectively cultured airway epithelial cells were available so far. Here, primary
      cells and immortalized cell lines from bats of the two important suborders
      Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short
      tailed bat) and Eidolon helvum (Straw-colored fruit bat), were successfully
      cultured under standardized conditions from both fresh and frozen organ specimens
      by cell outgrowth of organ explants and by the use of serum-free primary cell
      culture medium. Cells were immortalized to generate permanent cell lines. Cells
      were characterized for their epithelial properties such as expression of
      cytokeratin and tight junctions proteins and permissiveness for viral infection
      with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells
      can serve as suitable models for the study of bat-borne viruses and complement
      cell culture models for virus infection in human airway epithelial cells. 

PMID- 24454737
TI  - Comparisons between the 2012 new CKD-EPI (Chronic Kidney Disease Epidemiology
      Collaboration) equations and other four approved equations.
AB  - OBJECTIVE: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      reported two equations in 2012: one based on cystatin C concentration (CKD
      EPI2012cys) and the other using both serum creatinine and cystatin C
      concentrations (CKD-EPI2012Scr-cys). We compared the adaptability of new formulae
      with other four equations. METHODS: Participants (n = 788; median age, 54 [range,
      19-94] years) were recruited from the First Affiliated Hospital of Nanjing
      Medical University. The reference glomerular filtration rate (rGFR) was measured
      by a (99)mTc-DTPA renal dynamic imaging method, and the estimated glomerular
      filtration rate (eGFR) was calculated separately by the Chinese adapted
      Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum
      creatinine-based CKD-EPI equation (CKD-EPI2009Scr), CKD-EPI2012cys and CKD
      EPI2012Scr-cys equations. We compared the performance of six equations with rGFR.
      RESULTS: Median rGFR was 76.35 (interquartile range, 59.03-92.50) mL/min/1.73
      m(2). Compared with CKD-EPI2009Scr, CKD-EPI2012Scr-cys formula had better
      diagnostic value with larger area under the receiver operating characteristic
      curve (ROC(AUC), 0.879, p = 0.006), especially in young participants (ROC(AUC),
      0.883, p = 0.005). CKD-EPI2012cys equation did not perform better than other
      available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P30])
      of the CKD-EPI2012Scr-cys equation (77.03%) was inferior only to MacIsaac
      equation (80.2%) in the entire participants, but performed best in young
      participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI
      equations achieved any ideal P30 in the elderly participants with moderately
      severely injured GFR. Linear regression analysis demonstrated a consistent
      result. In this study, CKD-EPI2012Scr-cys had a relatively better diagnosis
      consistency of GFR stage between the eGFR and rGFR in the whole cohort.
      CONCLUSION: CKD-EPI2012Scr-cys appeared less biased and more accurate in overall
      participants. Neither of the new CKD-EPI equations achieved ideal accuracy in
      senior participants with moderately-severely injured GFR. A large-scale study
      with more subjects and cooperating centers to develop new formulae for the
      elderly is assumed to be necessary.

PMID- 24454738
TI  - Meta-analysis of repository data: impact of data regularization on NIMH
      schizophrenia linkage results.
AB  - Human geneticists are increasingly turning to study designs based on very large
      sample sizes to overcome difficulties in studying complex disorders. This in turn
      almost always requires multi-site data collection and processing of data through
      centralized repositories. While such repositories offer many advantages,
      including the ability to return to previously collected data to apply new
      analytic techniques, they also have some limitations. To illustrate, we reviewed
      data from seven older schizophrenia studies available from the NIMH-funded Center
      for Collaborative Genomic Studies on Mental Disorders, also known as the Human
      Genetics Initiative (HGI), and assessed the impact of data cleaning and
      regularization on linkage analyses. Extensive data regularization protocols were
      developed and applied to both genotypic and phenotypic data. Genome-wide
      nonparametric linkage (NPL) statistics were computed for each study, over various
      stages of data processing. To assess the impact of data processing on aggregate
      results, Genome-Scan Meta-Analysis (GSMA) was performed. Examples of increased,
      reduced and shifted linkage peaks were found when comparing linkage results based
      on original HGI data to results using post-processed data within the same set of
      pedigrees. Interestingly, reducing the number of affected individuals tended to
      increase rather than decrease linkage peaks. But most importantly, while the
      effects of data regularization within individual data sets were small, GSMA
      applied to the data in aggregate yielded a substantially different picture after
      data regularization. These results have implications for analyses based on other
      types of data (e.g., case-control GWAS or sequencing data) as well as data
      obtained from other repositories. 

PMID- 24454739
TI  - Novel genes participating in the formation of prismatic and nacreous layers in
      the pearl oyster as revealed by their tissue distribution and RNA interference
      knockdown.
AB  - In our previous publication, we identified novel gene candidates involved in
      shell formation by EST analyses of the nacreous and prismatic layer-forming
      tissues in the pearl oyster Pinctada fucata. In the present study, 14 of those
      genes, including two known genes, were selected and further examined for their
      involvement in shell formation using the RNA interference. Molecular
      characterization based on the deduced amino acid sequences showed that seven of
      the novel genes encode secretory proteins. The tissue distribution of the
      transcripts of the genes, as analyzed by RT-PCR and in situ hybridization, was
      mostly consistent with those obtained by the EST analysis reported previously.
      Shells in the pearl oysters injected with dsRNAs targeting genes 000027, 000058,
      000081, 000096, 000113 (nacrein), 000118, 000133 and 000411 (MSI60), which showed
      expression specific to the nacreous layer forming tissues, showed abnormal
      surface appearance in this layer. Individuals injected with dsRNAs targeting
      genes 000027, 000113 and 000133 also exhibited abnormal prismatic layers.
      Individuals injected with dsRNAs targeting genes 000031, 000066, 000098, 000145,
      000194 and 000200, which showed expression specific to prismatic layer forming
      tissues, displayed an abnormal surface appearance in both the nacreous and
      prismatic layers. Taken together, the results suggest that the genes involved in
      prismatic layer formation might also be involved in the formation of the nacreous
      layers. 

PMID- 24454740
TI  - Maternal snuff use and smoking and the risk of oral cleft malformations--a
      population-based cohort study.
AB  - OBJECTIVE: To determine if maternal use of snuff (containing high levels of
      nicotine, low levels of nitrosamines and no combustion products) is associated
      with an increased risk of oral cleft malformations in the infant and whether
      cessation of snuff use or smoking before the antenatal booking influences the
      risk. METHOD: A population-based cohort study was conducted on all live born
      infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n
      = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic
      regression analyses (using adjusted odds ratios, with 95% confidence intervals
      [CI]). RESULTS: Among 975 866 infants that had information on maternal tobacco
      use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who
      used snuff or smoked three months prior pregnancy stopped using before the
      antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking
      and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users,
      the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who
      continued to use snuff or to smoke were 1.48 [1.00-2.21] and 1.19 [1.01-1.41],
      respectively. In contrast, in infants of mothers who stopped using snuff or
      stopped smoking before the antenatal booking, the corresponding risks were not
      increased (adjusted odds ratios [95% CI] were 0.71 [0.44-1.14] and 0.88 [0.73
      1.05], respectively). CONCLUSION: Maternal snuff use or smoking in early
      pregnancy is associated with an increased risk of oral clefts. Infants of mothers
      who stopped using snuff or stopped smoking before the antenatal booking had no
      increased risk of oral cleft malformations. Oral snuff or other sources of
      nicotine should not be recommended as an alternative for smoke-cessation during
      pregnancy.

PMID- 24454741
TI  - Bioaccumulation of Cry1Ab protein from an herbivore reduces anti-oxidant enzyme
      activities in two spider species.
AB  - Cry proteins are expressed in rice lines for lepidopteran pest control. These
      proteins can be transferred from transgenic rice plants to non-target arthropods,
      including planthoppers and then to a predatory spider. Movement of Cry proteins
      through food webs may reduce fitness of non-target arthropods, although recent
      publications indicated no serious changes in non-target populations. Nonetheless,
      Cry protein intoxication influences gene expression in Cry-sensitive insects. We
      posed the hypothesis that Cry protein intoxication influences enzyme activities
      in spiders acting in tri-trophic food webs. Here we report on the outcomes of
      experiments designed to test our hypothesis with two spider species. We
      demonstrated that the movement of CryAb protein from Drosophila culture medium
      into fruit flies maintained on the CryAb containing medium and from the flies to
      the spiders Ummeliata insecticeps and Pardosa pseudoannulata. We also show that
      the activities of three key metabolic enzymes, acetylcholine esterase (AchE),
      glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were
      significantly influenced in the spiders after feeding on Cry1Ab-containing fruit
      flies. We infer from these data that Cry proteins originating in transgenic crops
      impacts non-target arthropods at the physiological and biochemical levels, which
      may be one mechanism of Cry protein-related reductions in fitness of non-target
      beneficial predators. 

PMID- 24454742
TI  - Characterization of pancreatic islets in two selectively bred mouse lines with
      different susceptibilities to high-fat diet-induced glucose intolerance.
AB  - Hereditary predisposition to diet-induced type 2 diabetes has not yet been fully
      elucidated. We recently established 2 mouse lines with different susceptibilities
      (resistant and prone) to high-fat diet (HFD)-induced glucose intolerance by
      selective breeding (designated selectively bred diet-induced glucose intolerance
      resistant [SDG-R] and -prone [SDG-P], respectively). To investigate the
      predisposition to HFD-induced glucose intolerance in pancreatic islets, we
      examined the islet morphological features and functions in these novel mouse
      lines. Male SDG-P and SDG-R mice were fed a HFD for 5 weeks. Before and after HFD
      feeding, glucose tolerance was evaluated by oral glucose tolerance test (OGTT).
      Morphometry and functional analyses of the pancreatic islets were also performed
      before and after the feeding period. Before HFD feeding, SDG-P mice showed
      modestly higher postchallenge blood glucose levels and lower insulin increments
      in OGTT than SDG-R mice. Although SDG-P mice showed greater beta cell
      proliferation than SDG-R mice under HFD feeding, SDG-P mice developed overt
      glucose intolerance, whereas SDG-R mice maintained normal glucose tolerance.
      Regardless of whether it was before or after HFD feeding, the isolated islets
      from SDG-P mice showed impaired glucose- and KCl-stimulated insulin secretion
      relative to those from SDG-R mice; accordingly, the expression levels of the
      insulin secretion-related genes in SDG-P islets were significantly lower than
      those in SDG-R islets. These findings suggest that the innate predispositions in
      pancreatic islets may determine the susceptibility to diet-induced diabetes. SDG
      R and SDG-P mice may therefore be useful polygenic animal models to study the
      gene-environment interactions in the development of type 2 diabetes. 

PMID- 24454743
TI  - Selection and evaluation of reference genes for expression analysis using qRT-PCR
      in the beet armyworm Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae).
AB  - Quantitative real-time PCR (qRT-PCR) is a reliable and reproducible technique for
      measuring and evaluating changes in gene expression. The most common method for
      analyzing qRT-PCR data is to normalize mRNA levels of target genes to internal
      reference genes. Evaluating and selecting stable reference genes on a case-by
      case basis is critical. The present study aimed to facilitate gene expression
      studies by identifying the most suitable reference genes for normalization of
      mRNA expression in qRT-PCR analysis of the beet armyworm Spodoptera exigua
      (Lepidoptera: Noctuidae). For this purpose, three software tools (geNorm,
      NormFinder and BestKeeper) were used to investigate 10 candidate reference genes
      in nine developmental stages and five different tissues (epidermis, head, midgut,
      fat body and hemolymph) in three larval physiological stages (molting, feeding
      and wandering stages) of, S. exigua. With the exception of 18S ribosomal RNA
      (18S), all other candidate genes evaluated, beta-actin1(ACT1), beta-actin2
      (ACT2), elongation factor1(EF1), elongation factor 2 (EF2), Glyceralde hyde-3
      phosphate dehydrogenase (GAPDH), ribosomal protein L10 (L10), ribosomal protein
      L17A (L17A), superoxide dismutase (SOD), alpha-tubulin (TUB),proved to be
      acceptable reference genes. However, their suitability partly differed between
      physiological stages and different tissues. L10, EF2 and L17A ranked highest in
      all tissue sample sets. SOD, ACT2, GAPDH, EF1 and ACT1 were stably expressed in
      all developmental stage sample sets; ACT2, ACT1 and L10 for larvae sample sets;
      GAPDH, ACT1 and ACT2 for pupae and adults; SOD and L17A for males; and EF2 and
      SOD for females. The expression stability of genes varied in different
      conditions. The findings provided here demonstrated, with a few exceptions, the
      suitability of most of the 10 reference genes tested in tissues and life
      developmental stages. Overall, this study emphasizes the importance of validating
      reference genes for qRT-PCR analysis in S. exigua. 

PMID- 24454744
TI  - An entomopathogenic strain of Beauveria bassiana against Frankliniella
      occidentalis with no detrimental effect on the predatory mite Neoseiulus barkeri:
      evidence from laboratory bioassay and scanning electron microscopic observation.
AB  - Among 28 isolates of Beauveria bassiana tested for virulence against F.
      occidentalis in laboratory bioassays, we found strain SZ-26 as the most potent,
      causing 96% mortality in adults at 1*10(7) mL(-1)conidia after 4 days. The effect
      of the strain SZ-26 on survival, longevity and fecundity of the predatory mite
      Neoseiulus (Amblyseius) barkeri Hughes were studied under laboratory conditions.
      The bioassay results showed that the corrected mortalities were less than 4 and
      8% at 10 days following inoculation of the adult and the larvae of the predator,
      respectively, with 1*10(7) conidia mL(-1) of SZ-26. Furthermore, no fungal hyphae
      were found in dead predators. The oviposition and postoviposition durations,
      longevity, and fecundity displayed no significant differences after inoculation
      with SZ-26 using first-instar larvae of F. occidentalis as prey in comparison
      with untreated predator. In contrast, the preoviposition durations were
      significantly longer. Observations with a scanning electron microscope, revealed
      that many conidia were attached to the cuticles of F. occidentalis at 2 h after
      treatment with germ tubes oriented toward cuticle at 24 h, penetration of the
      insect cuticle at 36 h, and finally, fungal colonization of the whole insect body
      at 60 h. In contrast, we never observed penetration of the predator's cuticle and
      conidia were shed gradually from the body, further demonstrating that B. bassiana
      strain SZ-26 show high toxicity against F. occidentalis but no pathogenicity to
      predatory mite. 

PMID- 24454745
TI  - Multi-modal use of a socially directed call in bonobos.
AB  - 'Contest hoots' are acoustically complex vocalisations produced by adult and
      subadult male bonobos (Pan paniscus). These calls are often directed at specific
      individuals and regularly combined with gestures and other body signals. The aim
      of our study was to describe the multi-modal use of this call type and to clarify
      its communicative and social function. To this end, we observed two large groups
      of bonobos, which generated a sample of 585 communicative interactions initiated
      by 10 different males. We found that contest hooting, with or without other
      associated signals, was produced to challenge and provoke a social reaction in
      the targeted individual, usually agonistic chase. Interestingly, 'contest hoots'
      were sometimes also used during friendly play. In both contexts, males were
      highly selective in whom they targeted by preferentially choosing individuals of
      equal or higher social rank, suggesting that the calls functioned to assert
      social status. Multi-modal sequences were not more successful in eliciting
      reactions than contest hoots given alone, but we found a significant difference
      in the choice of associated gestures between playful and agonistic contexts.
      During friendly play, contest hoots were significantly more often combined with
      soft than rough gestures compared to agonistic challenges, while the calls'
      acoustic structure remained the same. We conclude that contest hoots indicate the
      signaller's intention to interact socially with important group members, while
      the gestures provide additional cues concerning the nature of the desired
      interaction. 

PMID- 24454746
TI  - ABO genotype, 'blood-type' diet and cardiometabolic risk factors.
AB  - BACKGROUND: The 'Blood-Type' diet advises individuals to eat according to their
      ABO blood group to improve their health and decrease risk of chronic diseases
      such as cardiovascular disease. However, the association between blood type-based
      dietary patterns and health outcomes has not been examined. The objective of this
      study was to determine the association between 'blood-type' diets and biomarkers
      of cardiometabolic health and whether an individual's ABO genotype modifies any
      associations. METHODS: Subjects (n = 1,455) were participants of the Toronto
      Nutrigenomics and Health study. Dietary intake was assessed using a one-month,
      196-item food frequency questionnaire and a diet score was calculated to
      determine relative adherence to each of the four 'Blood-Type' diets. ABO blood
      group was determined by genotyping rs8176719 and rs8176746 in the ABO gene.
      ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to
      compare cardiometabolic biomarkers across tertiles of each 'Blood-Type' diet
      score. RESULTS: Adherence to the Type-A diet was associated with lower BMI, waist
      circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR
      and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with
      lower levels of these biomarkers (P<0.05), except for BMI and waist
      circumference. Adherence to the Type-O diet was associated with lower
      triglycerides (P<0.0001). Matching the 'Blood-Type' diets with the corresponding
      blood group did not change the effect size of any of these associations. No
      significant association was found for the Type-B diet. CONCLUSIONS: Adherence to
      certain 'Blood-Type' diets is associated with favorable effects on some
      cardiometabolic risk factors, but these associations were independent of an
      individual's ABO genotype, so the findings do not support the 'Blood-Type' diet
      hypothesis.

PMID- 24454747
TI  - Wildfire selectivity for land cover type: does size matter?
AB  - Previous research has shown that fires burn certain land cover types
      disproportionally to their abundance. We used quantile regression to study land
      cover proneness to fire as a function of fire size, under the hypothesis that
      they are inversely related, for all land cover types. Using five years of fire
      perimeters, we estimated conditional quantile functions for lower (avoidance) and
      upper (preference) quantiles of fire selectivity for five land cover types -
      annual crops, evergreen oak woodlands, eucalypt forests, pine forests and
      shrublands. The slope of significant regression quantiles describes the rate of
      change in fire selectivity (avoidance or preference) as a function of fire size.
      We used Monte-Carlo methods to randomly permutate fires in order to obtain a
      distribution of fire selectivity due to chance. This distribution was used to
      test the null hypotheses that 1) mean fire selectivity does not differ from that
      obtained by randomly relocating observed fire perimeters; 2) that land cover
      proneness to fire does not vary with fire size. Our results show that land cover
      proneness to fire is higher for shrublands and pine forests than for annual crops
      and evergreen oak woodlands. As fire size increases, selectivity decreases for
      all land cover types tested. Moreover, the rate of change in selectivity with
      fire size is higher for preference than for avoidance. Comparison between
      observed and randomized data led us to reject both null hypotheses tested
      ([Formula: see text] = 0.05) and to conclude it is very unlikely the observed
      values of fire selectivity and change in selectivity with fire size are due to
      chance. 

PMID- 24454748
TI  - The inter-arm diastolic blood pressure difference induced by one arm ischemia: a
      new approach to assess vascular endothelia function.
AB  - OBJECTIVES: To evaluate whether inter-arm diastolic blood pressure difference
      (DBPl-r) induced by one arm ischemia correlates with flow-mediated dilatation
      (FMD). METHODS: Bilateral arm BPs were simultaneously measured with two automatic
      devices and right brachial artery diameter (D) was measured by ultrasound
      technique in 108 subjects (56 hypertensives and 52 normotensives). Following
      baseline diameter (D0) and BP measurement, right brachial artery was occluded for
      5 minutes. The diameter was measured at 1, 1.5 and 2 min, and bilateral BPs
      measured at 3, 4 and 5 min after occlusion release. Their averages were recorded
      as post-D and post-BP, respectively. The difference between post-D and D0
      (DeltaD) was calculated as the percentage increase of artery diameter
      (DeltaD/D0). The BP difference between left and right arms was calculated as BPl
      r, and the difference of post- BPl-r and baseline BPl-r was recorded as the net
      change of BPl-r (DeltaBPl-r). RESULTS: At baseline, bilateral SBPs and DBPs were
      similar. Right arm ischemia induced significant DBP decline only in the right arm
      (68.8+/-12.7 vs 72.6+/-12.0 mmHg, P<0.05), which led to an increase of DeltaDBPl
      r (4.00+/-3.75 vs 0.78+/-4.47 mmHg, P<0.05). A positive correlation was seen
      between DeltaD/D0 and DeltaDBPl-r (r = 0.744, p<0.001). Furthermore, the
      correlation between age and DeltaDBPl-r (r = -0.358, P<0.01) was similar to that
      between age and D/D0 (r = -0.398, P<0.01). Meanwhile, both DeltaDBPl-r and
      DeltaD/D0 were significantly lower in hypertensive patients than in normotensive
      patients. CONCLUSION: The inter-arm DBP difference induced by one arm ischemia
      may be a potential index for clinical evaluation of vascular endothelial
      function.

PMID- 24454749
TI  - Genome-wide analysis of the MADS-box gene family in Brachypodium distachyon.
AB  - MADS-box genes are important transcription factors for plant development,
      especially floral organogenesis. Brachypodium distachyon is a model for biofuel
      plants and temperate grasses such as wheat and barley, but a comprehensive
      analysis of MADS-box family proteins in Brachypodium is still missing. We report
      here a genome-wide analysis of the MADS-box gene family in Brachypodium
      distachyon. We identified 57 MADS-box genes and classified them into 32 MIKC(c)
      type, 7 MIKC*-type, 9 Malpha, 7 Mbeta and 2 Mgamma MADS-box genes according to
      their phylogenetic relationships to the Arabidopsis and rice MADS-box genes.
      Detailed gene structure and motif distribution were then studied. Investigation
      of their chromosomal localizations revealed that Brachypodium MADS-box genes
      distributed evenly across five chromosomes. In addition, five pairs of type II
      MADS-box genes were found on synteny blocks derived from whole genome duplication
      blocks. We then performed a systematic expression analysis of Brachypodium MADS
      box genes in various tissues, particular floral organs. Further detection under
      salt, drought, and low-temperature conditions showed that some MADS-box genes may
      also be involved in abiotic stress responses, including type I genes. Comparative
      studies of MADS-box genes among Brachypodium, rice and Arabidopsis showed that
      Brachypodium had fewer gene duplication events. Taken together, this work
      provides useful data for further functional studies of MADS-box genes in
      Brachypodium distachyon. 

PMID- 24454750
TI  - Muscle fiber viability, a novel method for the fast detection of ischemic muscle
      injury in rats.
AB  - Acute lower extremity ischemia is a limb- and life-threatening clinical problem.
      Rapid detection of the degree of injury is crucial, however at present there are
      no exact diagnostic tests available to achieve this purpose. Our goal was to
      examine a novel technique - which has the potential to accurately assess the
      degree of ischemic muscle injury within a short period of time - in a clinically
      relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of
      bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta.
      Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of
      reperfusion to examine the effects of revascularization. Muscle samples were
      collected from the left anterior tibial muscle for viability assessment. The
      degree of muscle damage (muscle fiber viability) was assessed by morphometric
      evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind
      limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and
      electron microscopic examinations. Muscle fiber viability decreased progressively
      over the time of ischemia, with significant differences found between the
      consecutive times. High correlation was detected between the length of ischemia
      and the values of muscle fiber viability. After reperfusion, viability showed
      significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group
      compared to the 8-hour-ischemia-only group, and decreased further after 9 hours
      of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings
      correlated strongly with the values of muscle fiber viability: lesser viability
      values represented higher degree of ultrastructural injury while similar
      viability results corresponded to similar morphological injury. Muscle fiber
      viability was capable of accurately determining the degree of muscle injury in
      our rat model. Our method might therefore be useful in clinical settings in the
      diagnostics of acute ischemic muscle injury. 

PMID- 24454751
TI  - Disulfiram eradicates tumor-initiating hepatocellular carcinoma cells in ROS-p38
      MAPK pathway-dependent and -independent manners.
AB  - Tumor-initiating cells (TICs) play a central role in tumor development,
      metastasis, and recurrence. In the present study, we investigated the effect of
      disulfiram (DSF), an inhibitor of aldehyde dehydrogenase, toward tumor-initiating
      hepatocellular carcinoma (HCC) cells. DSF treatment suppressed the anchorage
      independent sphere formation of both HCC cells. Flow cytometric analyses showed
      that DSF but not 5-fluorouracil (5-FU) drastically reduces the number of tumor
      initiating HCC cells. The sphere formation assays of epithelial cell adhesion
      molecule (EpCAM)(+) HCC cells co-treated with p38-specific inhibitor revealed
      that DSF suppresses self-renewal capability mainly through the activation of
      reactive oxygen species (ROS)-p38 MAPK pathway. Microarray experiments also
      revealed the enrichment of the gene set involved in p38 MAPK signaling in
      EpCAM(+) cells treated with DSF but not 5-FU. In addition, DSF appeared to
      downregulate Glypican 3 (GPC3) in a manner independent of ROS-p38 MAPK pathway.
      GPC3 was co-expressed with EpCAM in HCC cell lines and primary HCC cells and GPC3
      knockdown reduced the number of EpCAM(+) cells by compromising their self-renewal
      capability and inducing the apoptosis. These results indicate that DSF impaired
      the tumorigenicity of tumor-initiating HCC cells through activation of ROS-p38
      pathway and in part through the downregulation of GPC3. DSF might be a promising
      therapeutic agent for the eradication of tumor-initiating HCC cells. 

PMID- 24454752
TI  - General practitioners can evaluate the material, social and health dimensions of
      patient social status.
AB  - OBJECTIVE: To identify which physician and patient characteristics are associated
      with physicians' estimation of their patient social status. DESIGN: Cross
      sectional multicentric survey. SETTING: Fourty-seven primary care private offices
      in Western Switzerland. PARTICIPANTS: Random sample of 2030 patients >= 16, who
      encountered a general practitioner (GP) between September 2010 and February 2011.
      MAIN MEASURES:  PRIMARY OUTCOME: patient social status perceived by GPs, using
      the MacArthur Scale of Subjective Social Status, ranging from the bottom (0) to
      the top (10) of the social scale.Secondary outcome: Difference between GP's
      evaluation and patient's own evaluation of their social status. Potential patient
      correlates: material and social deprivation using the DiPCare-Q, health status
      using the EQ-5D, sources of income, and level of education. GP characteristics:
      opinion regarding patients' deprivation and its influence on health and care.
      RESULTS: To evaluate patient social status, GPs considered the material, social,
      and health aspects of deprivation, along with education level, and amount and
      type of income. GPs declaring a frequent reflexive consideration of their own
      prejudice towards deprived patients, gave a higher estimation of patients' social
      status (+1.0, p = 0.002). Choosing a less costly treatment for deprived patients
      was associated with a lower estimation (-0.7, p = 0.002). GP's evaluation of
      patient social status was 0.5 point higher than the patient's own estimate
      (p<0.0001). CONCLUSIONS: GPs can perceive the various dimensions of patient
      social status, although heterogeneously, according partly to their own
      characteristics. Compared to patients' own evaluation, GPs overestimate patient
      social status.

PMID- 24454753
TI  - Atp6v1c1 may regulate filament actin arrangement in breast cancer cells.
AB  - Previous studies have shown that the rate of breast cancer metastasis correlates
      with the expression of vacuolar H(+)-ATPases (V-ATPases). However, how V-ATPase
      is involved in breast cancer metastasis remains unknown. Our previous study
      showed that Atp6v1c1-depleted osteoclasts did not form organized actin rings and
      that Atp6v1c1 co-localizes with F-actin. In this study, we found that the normal
      arrangement of filamentous actin is disrupted in Atp6v1c1-depleted 4T1 mouse
      breast cancer cells and in the ATP6V1C1-depleted human breast cancer cell lines
      MDA-MB-231 and MDA-MB-435s. We further found that Atp6v1c1 co-localizes with F
      actin in 4T1 cells. The results of our study suggest that high expression of
      Atp6v1c1 affects the actin structure of cancer cells such that it facilitates
      breast cancer metastasis. The findings also indicate that Atp6v1c1 could be a
      novel target for breast cancer metastasis therapy. 

PMID- 24454755
TI  - What magnitude are observed non-target impacts from weed biocontrol?
AB  - A systematic review focused by plant on non-target impacts from agents
      deliberately introduced for the biological control of weeds found significant non
      target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents
      on 140 non-target plants was retrospectively categorized using a risk management
      framework for ecological impacts of invasive species (minimal, minor, moderate,
      major, massive). The vast majority of agents introduced for classical biological
      control of weeds (>99% of 512 agents released) have had no known significant
      adverse effects on non-target plants thus far; major effects suppressing non
      target plant populations could be expected to be detectable. Most direct non
      target impacts on plants (91.6%) were categorized as minimal or minor in
      magnitude with no known adverse long-term impact on non-target plant populations,
      but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to
      massive (n = 1) scale. The largest direct impacts are from two agents
      (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native
      thistles), but these introductions would not be permitted today as more balanced
      attitudes exist to plant biodiversity, driven by both society and the scientific
      community. Our analysis shows (as far as is known), weed biological control
      agents have a biosafety track record of >99% of cases avoiding significant non
      target impacts on plant populations. Some impacts could have been overlooked, but
      this seems unlikely to change the basic distribution of very limited adverse
      effects. Fewer non-target impacts can be expected in future because of improved
      science and incorporation of wider values. Failure to use biological control
      represents a significant opportunity cost from the certainty of ongoing adverse
      impacts from invasive weeds. It is recommended that a simple five-step scale be
      used to better communicate the risk of consequences from both action (classical
      biological control) and no action (ongoing impacts from invasive weeds). 

PMID- 24454754
TI  - The effect of brain-derived neurotrophic factor on periodontal furcation defects.
AB  - This study aimed to observe the regenerative effect of brain-derived neurotrophic
      factor (BDNF) in a non-human primate furcation defect model. Class II furcation
      defects were created in the first and second molars of 8 non-human primates to
      simulate a clinical situation. The defect was filled with either, Group A: BDNF
      (500 ug/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50
      ug/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E:
      BDNF (500 ug/ml) in saline. The healing status for all groups was observed at
      different time-points with micro computed tomography. The animals were euthanized
      after 11 weeks, and the tooth-bone specimens were subjected to histologic
      processing. The results showed that all groups seemed to successfully regenerate
      the alveolar buccal bone, however, only Group A regenerated the entire
      periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is
      suggested that the use of BDNF in combination with a scaffold such as the
      hyaluronic acid in periodontal furcation defects may be an effective treatment
      option. 

PMID- 24454756
TI  - STORMSeq: an open-source, user-friendly pipeline for processing personal genomics
      data in the cloud.
AB  - The increasing public availability of personal complete genome sequencing data
      has ushered in an era of democratized genomics. However, read mapping and variant
      calling software is constantly improving and individuals with personal genomic
      data may prefer to customize and update their variant calls. Here, we describe
      STORMSeq (Scalable Tools for Open-Source Read Mapping), a graphical interface
      cloud computing solution that does not require a parallel computing environment
      or extensive technical experience. This customizable and modular system performs
      read mapping, read cleaning, and variant calling and annotation. At present,
      STORMSeq costs approximately $2 and 5-10 hours to process a full exome sequence
      and $30 and 3-8 days to process a whole genome sequence. We provide this open
      access and open-source resource as a user-friendly interface in Amazon EC2. 

PMID- 24454757
TI  - Cumulative sum analysis for experiences of a single-session retrograde intrarenal
      stone surgery and analysis of predictors for stone-free status.
AB  - INTRODUCTION: This study investigated the learning curve of a single-session
      retrograde intrarenal surgery (RIRS) in patients with mid-sized stones.
      Competence and trainee proficiency for RIRS was assessed using cumulative sum
      analysis (CUSUM). MATERIALS AND METHODS: The study design and the use of
      patients' information stored in the hospital database were approved by the
      Institutional Review Board of our institution. A retrospective review was
      performed for 100 patients who underwent a single-session RIRS. Patients were
      included if the main stone had a maximal diameter between 10 and 30 mm. The
      presence of a residual stone was checked on postoperative day 1 and at one-month
      follow-up visit. Fragmentation efficacy was calculated "removed stone volume
      (mm(3)) divided by operative time (min)". CUSUM analysis was used for monitoring
      change in fragmentation efficacy, and we tested whether or not acceptable
      surgical outcomes were achieved. RESULTS: The mean age was 54.7+/-14.8 years.
      Serum creatinine level did not change significantly. Estimated GFR and hemoglobin
      were within normal limits postoperatively. The CUSUM curve tended to be flat
      until the 25th case and showed a rising pattern but declined again until the 56th
      case. After that point, the fragmentation efficacy reached a plateau. The
      acceptable level of fragmentation efficacy was 25 ml/min. Multivariate logistic
      regression analyses showed that stone-free rate was significantly lower for cases
      with multiple stones than those with a single stone (OR = 0.147, CI 0.032 -
      0.674, P value  = 0.005) and for cases with higher number of sites (OR = 0.676,
      CI 0.517 - 0.882, P value  = 0.004). CONCLUSIONS: The statistical analysis of
      RIRS learning experience revealed that 56 cases were required for reaching a
      plateau in the learning curve. The number of stones and the number of sites were
      significant predictors for stone-free status.

PMID- 24454758
TI  - Efficient and rapid induction of human iPSCs/ESCs into nephrogenic intermediate
      mesoderm using small molecule-based differentiation methods.
AB  - The first step in developing regenerative medicine approaches to treat renal
      diseases using pluripotent stem cells must be the generation of intermediate
      mesoderm (IM), an embryonic germ layer that gives rise to kidneys. In order to
      achieve this goal, establishing an efficient, stable and low-cost method for
      differentiating IM cells using small molecules is required. In this study, we
      identified two retinoids, AM580 and TTNPB, as potent IM inducers by high
      throughput chemical screening, and established rapid (five days) and efficient
      (80% induction rate) IM differentiation from human iPSCs using only two small
      molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or
      TTNPB. The resulting human IM cells showed the ability to differentiate into
      multiple cell types that constitute adult kidneys, and to form renal tubule-like
      structures. These small molecule differentiation methods can bypass the
      mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid
      (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful
      tools for studying kidney development and may potentially provide cell sources to
      generate renal lineage cells for regenerative therapy. 

PMID- 24454760
TI  - How cheap is soaring flight in raptors? A preliminary investigation in freely
      flying vultures.
AB  - Measuring the costs of soaring, gliding and flapping flight in raptors is
      challenging, but essential for understanding their ecology. Among raptors,
      vultures are scavengers that have evolved highly efficient soaring-gliding flight
      techniques to minimize energy costs to find unpredictable food resources. Using
      electrocardiogram, GPS and accelerometer bio-loggers, we report the heart rate
      (HR) of captive griffon vultures (Gyps fulvus and G. himalayensis) trained for
      freely-flying. HR increased three-fold at take-off (characterized by prolonged
      flapping flight) and landing (>300 beats-per-minute, (bpm)) compared to baseline
      levels (80-100 bpm). However, within 10 minutes after the initial flapping phase,
      HR in soaring/gliding flight dropped to values similar to baseline levels, i.e.
      slightly lower than theoretically expected. However, the extremely rapid decrease
      in HR was unexpected, when compared with other marine gliders, such as
      albatrosses. Weather conditions influenced flight performance and HR was
      noticeably higher during cloudy compared to sunny conditions when prolonged
      soaring flight is made easier by thermal ascending air currents. Soaring as a
      cheap locomotory mode is a crucial adaptation for vultures who spend so long on
      the wing for wide-ranging movements to find food. 

PMID- 24454759
TI  - Olives and olive oil are sources of electrophilic fatty acid nitroalkenes.
AB  - Extra virgin olive oil (EVOO) and olives, key sources of unsaturated fatty acids
      in the Mediterranean diet, provide health benefits to humans. Nitric oxide (*NO)
      and nitrite (NO2 (-))-dependent reactions of unsaturated fatty acids yield
      electrophilic nitroalkene derivatives (NO2-FA) that manifest salutary pleiotropic
      cell signaling responses in mammals. Herein, the endogenous presence of NO2-FA in
      both EVOO and fresh olives was demonstrated by mass spectrometry. The
      electrophilic nature of these species was affirmed by the detection of
      significant levels of protein cysteine adducts of nitro-oleic acid (NO2-OA
      cysteine) in fresh olives, especially in the peel. Further nitration of EVOO by
      NO2 (-) under acidic gastric digestive conditions revealed that human consumption
      of olive lipids will produce additional nitro-conjugated linoleic acid (NO2-cLA)
      and nitro-oleic acid (NO2-OA). The presence of free and protein-adducted NO2-FA
      in both mammalian and plant lipids further affirm a role for these species as
      signaling mediators. Since NO2-FA instigate adaptive anti-inflammatory gene
      expression and metabolic responses, these redox-derived metabolites may
      contribute to the cardiovascular benefits associated with the Mediterranean diet.

PMID- 24454761
TI  - Transgenic expression of soluble human CD5 enhances experimentally-induced
      autoimmune and anti-tumoral immune responses.
AB  - CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on
      thymocytes and mature T and B1a lymphocytes. Current data support the view that
      CD5 is a negative regulator of antigen-specific receptor-mediated signaling in
      these cells, and that this would likely be achieved through interaction with CD5
      ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells.
      To determine the functional consequence of loss of CD5/CD5L interaction in vivo,
      a new transgenic mouse line was generated (shCD5EMUTg), expressing a circulating
      soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5
      function. These shCD5EMUTg mice showed an enhanced response to autologous
      antigens, as deduced from the presentation of more severe forms of experimentally
      inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental
      autoimmune encephalitis, EAE), as well as an increased anti-tumoral response in
      non-orthotopic cancer models (B16 melanoma). This enhancement of the immune
      response was in agreement with the finding of significantly reduced proportions
      of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10
      producing and CD5+ B cells, as well as an increased proportion of spleen NKT
      cells in shCD5EMUTg mice. Similar changes in lymphocyte subpopulations were
      observed in wild-type mice following repeated administration of exogenous
      recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L
      interactions on the homeostasis of some functionally relevant lymphocyte
      subpopulations and the modulation of immune responses to autologous antigens. 

PMID- 24454762
TI  - Ubiquitin-specific protease 5 is required for the efficient repair of DNA double
      strand breaks.
AB  - During the DNA damage response (DDR), ubiquitination plays an important role in
      the recruitment and regulation of repair proteins. However, little is known about
      elimination of the ubiquitination signal after repair is completed. Here we show
      that the ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, is
      involved in the elimination of the ubiquitin signal from damaged sites and is
      required for efficient DNA double-strand break (DSB) repair. Depletion of USP5
      sensitizes cells to DNA damaging agents, produces DSBs, causes delayed
      disappearance of gammaH2AX foci after Bleocin treatment, and influences DSB
      repair efficiency in the homologous recombination pathway but not in the non
      homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro
      irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at
      sites of DNA damage remained for longer periods in USP5-depleted cells. Our
      results show that disassembly of polyubiquitin chains by USP5 at sites of damage
      is important for efficient DSB repair. 

PMID- 24454763
TI  - Inhibition of c-Kit is not required for reversal of hyperglycemia by imatinib in
      NOD mice.
AB  - AIM/HYPOTHESIS: Recent studies indicate that tyrosine kinase inhibitors,
      including imatinib, can reverse hyperglycemia in non-obese diabetic (NOD) mice, a
      model of type 1 diabetes (T1D). Imatinib inhibits c-Abl, c-Kit, and PDGFRs. Next
      generation tyrosine kinase inhibitors for T1D treatment should maintain
      activities required for efficacy while sparing inhibition of targets that might
      otherwise lead to adverse events. In this study, we investigated the contribution
      of c-Kit inhibition by imatinib in reversal of hyperglycemia in NOD mice.
      METHODS: The T670I mutation in c-Kit, which confers imatinib resistance, was
      engineered into the mouse genome and bred onto the NOD background. Hematopoietic
      stem cells (HSCs) from NOD.c-Kit(T670I) mice and NOD.c-Kit(wt) littermates were
      expanded in the presence or absence of imatinib to verify imatinib resistance of
      the c-Kit(T670I) allele. Diabetic mice were treated with imatinib at the onset of
      hyperglycemia for three weeks, and blood glucose was monitored. RESULTS: In vitro
      expansion of HSCs from NOD.c-Kit(wt) mice was sensitive to imatinib, while
      expansion of HSCs from NOD.c-Kit(T670I) mice was insensitive to imatinib.
      However, in vivo treatment with imatinib lowered blood glucose levels in both
      strains of mice. CONCLUSIONS/INTERPRETATION: The HSC experiment confirmed that,
      in NOD.c-Kit(T670I) mice, c-Kit is resistant to imatinib. As both NOD.c
      Kit(T670I) and NOD.c-Kit(wt) mice responded comparably to imatinib, c-Kit
      inhibition does not substantially contribute to the efficacy of imatinib in T1D.
      Thus, we conclude that inhibition of c-Kit is not required in next-generation
      tyrosine kinase inhibitors for T1D treatment, and may be selected against to
      improve the safety profile.

PMID- 24454764
TI  - Bmp6 expression can be regulated independently of liver iron in mice.
AB  - The liver is the primary organ for storing iron and plays a central role in the
      regulation of body iron levels by secretion of the hormone Hamp1. Although many
      factors modulate Hamp1 expression, their regulatory mechanisms are poorly
      understood. Here, we used conditional knockout mice for the iron exporter
      ferroportin1 (Fpn1) to modulate tissue iron in specific tissues in combination
      with iron-deficient or iron-rich diets and transferrin (Tf) supplementation to
      investigate the mechanisms underlying Hamp1 expression. Despite liver iron
      overload, expression of bone morphogenetic protein 6 (Bmp6), a potent-stimulator
      of Hamp1 expression that is expressed under iron-loaded conditions, was
      decreased. We hypothesized that factors other than liver iron must play a role in
      controlling Bmp6 expression. Our results show that erythropoietin and Tf-bound
      iron do not underlie the down-regulation of Bmp6 in our mice models. Moreover,
      Bmp6 was down-regulated under conditions of high iron demand, irrespective of the
      presence of anemia. We therefore inferred that the signals were driven by high
      iron demand. Furthermore, we also confirmed previous suggestions that Tf-bound
      iron regulates Hamp1 expression via Smad1/5/8 phosphorylation without affecting
      Bmp6 expression, and the effect of Tf-bound iron on Hamp1 regulation appeared
      before a significant change in Bmp6 expression. Together, these results are
      consistent with novel mechanisms for regulating Bmp6 and Hamp1 expression. 

PMID- 24454766
TI  - Insights into hepatopancreatic functions for nutrition metabolism and ovarian
      development in the crab Portunus trituberculatus: gene discovery in the
      comparative transcriptome of different hepatopancreas stages.
AB  - The crustacean hepatopancreas has different functions including absorption,
      storage of nutrients and vitellogenesis during growth, and ovarian development.
      However, genetic information on the biological functions of the crustacean
      hepatopancreas during such processes is limited. The swimming crab, Portunus
      trituberculatus, is a commercially important species for both aquaculture and
      fisheries in the Asia-Pacific region. This study compared the transcriptome in
      the hepatopancreas of female P. trituberculatus during the growth and ovarian
      maturation stages by 454 high-throughput pyrosequencing and bioinformatics. The
      goal was to discover genes in the hepatopancreas involved in food digestion,
      nutrition metabolism and ovarian development, and to identify patterns of gene
      expression during growth and ovarian maturation. Our transcriptome produced
      303,450 reads with an average length of 351 bp, and the high quality reads were
      assembled into 21,635 contigs and 31,844 singlets. Based on BLASTP searches of
      the deduced protein sequences, there were 7,762 contigs and 4,098 singlets with
      functional annotation. Further analysis revealed 33,427 unigenes with ORFs,
      including 17,388 contigs and 16,039 singlets in the hepatopancreas, while only
      7,954 unigenes (5,691 contigs and 2,263 singlets) with the predicted protein
      sequences were annotated with biological functions. The deduced protein sequences
      were assigned to 3,734 GO terms, 25 COG categories and 294 specific pathways.
      Furthermore, there were 14, 534, and 22 identified unigenes involved in food
      digestion, nutrition metabolism and ovarian development, respectively. 212
      differentially expressed genes (DEGs) were found between the growth and
      endogenous stage of the hepatopancreas, while there were 382 DEGs between the
      endogenous and exogenous stage hepatopancreas. Our results not only enhance the
      understanding of crustacean hepatopancreatic functions during growth and ovarian
      development, but also represent a basis for further research on new genes and
      functional genomics of P. trituberculatus or closely related species. 

PMID- 24454765
TI  - Adolescent brain maturation and cortical folding: evidence for reductions in
      gyrification.
AB  - Evidence from anatomical and functional imaging studies have highlighted major
      modifications of cortical circuits during adolescence. These include reductions
      of gray matter (GM), increases in the myelination of cortico-cortical connections
      and changes in the architecture of large-scale cortical networks. It is currently
      unclear, however, how the ongoing developmental processes impact upon the folding
      of the cerebral cortex and how changes in gyrification relate to maturation of
      GM/WM-volume, thickness and surface area. In the current study, we acquired high
      resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy
      subjects (34 males and 45 females) between the ages of 12 and 23 years and
      performed whole brain analysis of cortical folding patterns with the gyrification
      index (GI). In addition to GI-values, we obtained estimates of cortical
      thickness, surface area, GM and white matter (WM) volume which permitted
      correlations with changes in gyrification. Our data show pronounced and
      widespread reductions in GI-values during adolescence in several cortical regions
      which include precentral, temporal and frontal areas. Decreases in gyrification
      overlap only partially with changes in the thickness, volume and surface of GM
      and were characterized overall by a linear developmental trajectory. Our data
      suggest that the observed reductions in GI-values represent an additional,
      important modification of the cerebral cortex during late brain maturation which
      may be related to cognitive development. 

PMID- 24454767
TI  - Assessing quantitative resistance against Leptosphaeria maculans (phoma stem
      canker) in Brassica napus (oilseed rape) in young plants.
AB  - Quantitative resistance against Leptosphaeria maculans in Brassica napus is
      difficult to assess in young plants due to the long period of symptomless growth
      of the pathogen from the appearance of leaf lesions to the appearance of canker
      symptoms on the stem. By using doubled haploid (DH) lines A30 (susceptible) and
      C119 (with quantitative resistance), quantitative resistance against L. maculans
      was assessed in young plants in controlled environments at two stages: stage 1,
      growth of the pathogen along leaf veins/petioles towards the stem by leaf lamina
      inoculation; stage 2, growth in stem tissues to produce stem canker symptoms by
      leaf petiole inoculation. Two types of inoculum (ascospores; conidia) and three
      assessment methods (extent of visible necrosis; symptomless pathogen growth
      visualised using the GFP reporter gene; amount of pathogen DNA quantified by PCR)
      were used. In stage 1 assessments, significant differences were observed between
      lines A30 and C119 in area of leaf lesions, distance grown along veins/petioles
      assessed by visible necrosis or by viewing GFP and amount of L. maculans DNA in
      leaf petioles. In stage 2 assessments, significant differences were observed
      between lines A30 and C119 in severity of stem canker and amount of L. maculans
      DNA in stem tissues. GFP-labelled L. maculans spread more quickly from the stem
      cortex to the stem pith in A30 than in C119. Stem canker symptoms were produced
      more rapidly by using ascospore inoculum than by using conidial inoculum. These
      results suggest that quantitative resistance against L. maculans in B. napus can
      be assessed in young plants in controlled conditions. Development of methods to
      phenotype quantitative resistance against plant pathogens in young plants in
      controlled environments will help identification of stable quantitative
      resistance for control of crop diseases. 

PMID- 24454768
TI  - Reduction in ultrasonic vocalizations in pups born to rapid eye movement sleep
      restricted mothers in rat model.
AB  - The effects of rapid eye movement sleep restriction (REMSR) in rats during late
      pregnancy were studied on the ultrasonic vocalizations (USVs) made by the pups.
      USVs are distress calls inaudible to human ears. Rapid eye movement (REM) sleep
      was restricted in one group of pregnant rats for 22 hours, starting from
      gestational day 14 to 20, using standard single platform method. The USVs of male
      pups were recorded after a brief isolation from their mother for two minutes on
      alternate post-natal days, from day one till weaning. The USVs were recorded
      using microphones and were analysed qualitatively and quantitatively using SASPro
      software. Control pups produced maximum vocalization on post-natal days 9 to 11.
      In comparison, the pups born to REMSR mothers showed not only a reduction in
      vocalization but also a delay in peak call making days. The experimental group
      showed variations in the types and characteristics of call types, and alteration
      in temporal profile. The blunting of distress call making response in these pups
      indicates that maternal sleep plays a role in regulating the neural development
      involved in vocalizations and possibly in shaping the emotional behaviour in
      neonates. It is suggested that the reduced ultrasonic vocalizations can be
      utilized as a reliable early marker for affective state in rat pups. Such
      impaired vocalization responses could provide an important lead in understanding
      mother-child bonding for an optimal cognitive development during post-partum
      life. This is the first report showing a potential link between maternal REM
      sleep deprivation and the vocalization in neonates and infants. 

PMID- 24454769
TI  - Correlations and scaling laws in human mobility.
AB  - BACKGROUND: In recent years, several path-breaking findings on human mobility
      patterns point out a novel issue which is of important theoretical significance
      and great application prospects. The empirical analysis of the data which can
      reflect the real-world human mobility provides the basic cognition and
      verification of the theoretical models and predictive results on human mobility.
      One of the most noticeable findings in previous studies on human mobility is the
      wide-spread scaling anomalies, e.g. the power-law-like displacement
      distributions. Understanding the origin of these scaling anomalies is of central
      importance to this issue and therefore is the focus of our discussion.
      METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we empirically analyze the real
      world human movements which are based on GPS records, and observe rich scaling
      properties in the temporal-spatial patterns as well as an abnormal transition in
      the speed-displacement patterns together with an evidence to the real-world
      traffic jams. In addition, we notice that the displacements at the population
      level show a significant positive correlation, indicating a cascading-like nature
      in human movements. Furthermore, our analysis at the individual level finds that
      the displacement distributions of users with stronger correlations usually are
      closer to the power law, suggesting a correlation between the positive
      correlation of the displacement series and the form of an individual's
      displacement distribution. CONCLUSIONS/SIGNIFICANCE: These empirical findings
      make connections between the two basic properties of human mobility, the scaling
      anomalies on displacement distributions and the positive correlations on
      displacement series, implying the cascading-like dynamics which is exhibited by
      the positive correlations would cause the emergence of scaling properties on
      human mobility patterns. Our findings would inspire further researches on
      mechanisms and predictions of human mobility.

PMID- 24454770
TI  - Furin is the major proprotein convertase required for KISS1-to-Kisspeptin
      processing.
AB  - KISS1 is a broadly functional secreted proprotein that is then processed into
      small peptides, termed kisspeptins (KP). Since sequence analysis showed cleavage
      at KR or RR dibasic sites of the nascent protein, it was hypothesized that
      enzyme(s) belonging to the proprotein convertase family of proteases process
      KISS1 to generate KP. To this end, cell lines over-expressing KISS1 were treated
      with the proprotein convertase inhibitors, Dec-RVKR-CMK and alpha1-PDX, and KISS1
      processing was completely inhibited. To identify the specific enzyme(s)
      responsible for KISS1 processing, mRNA expression was systematically analyzed for
      six proprotein convertases found in secretory pathways. Consistent expression of
      the three proteases - furin, PCSK5 and PCSK7 - were potentially implicated in
      KISS1 processing. However, shRNA-mediated knockdown of furin - but not PCSK5 or
      PCSK7 - blocked KISS1 processing. Thus, furin appears to be the essential enzyme
      for the generation of kisspeptins. 

PMID- 24454771
TI  - Recruiting human microbiome shotgun data to site-specific reference genomes.
AB  - The human body consists of innumerable multifaceted environments that predispose
      colonization by a number of distinct microbial communities, which play
      fundamental roles in human health and disease. In addition to community surveys
      and shotgun metagenomes that seek to explore the composition and diversity of
      these microbiomes, there are significant efforts to sequence reference microbial
      genomes from many body sites of healthy adults. To illustrate the utility of
      reference genomes when studying more complex metagenomes, we present a reference
      based analysis of sequence reads generated from 55 shotgun metagenomes, selected
      from 5 major body sites, including 16 sub-sites. Interestingly, between 13% and
      92% (62.3% average) of these shotgun reads were aligned to a then-complete list
      of 2780 reference genomes, including 1583 references for the human microbiome.
      However, no reference genome was universally found in all body sites. For any
      given metagenome, the body site-specific reference genomes, derived from the same
      body site as the sample, accounted for an average of 58.8% of the mapped reads.
      While different body sites did differ in abundant genera, proximal or symmetrical
      body sites were found to be most similar to one another. The extent of variation
      observed, both between individuals sampled within the same microenvironment, or
      at the same site within the same individual over time, calls into question
      comparative studies across individuals even if sampled at the same body site.
      This study illustrates the high utility of reference genomes and the need for
      further site-specific reference microbial genome sequencing, even within the
      already well-sampled human microbiome. 

PMID- 24454772
TI  - Seasonal mesophotic coral bleaching of Stylophora pistillata in the Northern Red
      Sea.
AB  - Coral bleaching occurs when environmental stress induces breakdown of the coral
      algae symbiosis and the host initiates algae expulsion. Two types of coral
      bleaching had been thoroughly discussed in the scientific literature; the first
      is primarily associated with mass coral bleaching events; the second is a
      seasonal loss of algae and/or pigments. Here, we describe a phenomenon that has
      been witnessed for repeated summers in the mesophotic zone (40-63 m) in the
      northern Red Sea: seasonal bleaching and recovery of several hermatypic coral
      species. In this study, we followed the recurring bleaching process of the common
      coral Stylophora pistillata. Bleaching occurred from April to September with a
      66% decline in chlorophyll a concentration, while recovery began in October.
      Using aquarium and transplantation experiments, we explored environmental factors
      such as temperature, photon flux density and heterotrophic food availability. Our
      experiments and observations did not yield one single factor, alone, responsible
      for the seasonal bleaching. The dinoflagellate symbionts (of the genus
      Symbiodinium) in shallow (5 m) Stylophora pistillata were found to have a net
      photosynthetic rate of 56.98-92.19 umol O2 cm(-2) day(-1). However, those from
      mesophotic depth (60 m) during months when they are not bleached are net
      consumers of oxygen having a net photosynthetic rate between -12.86 - (-10.24)
      umol O2 cm(-2) day(-1). But during months when these mesophotic corals are
      partially-bleached, they yielded higher net production, between -2.83-0.76 umol
      O2 cm(-2) day(-1). This study opens research questions as to why mesophotic
      zooxanthellae are more successfully meeting the corals metabolic requirements
      when Chl a concentration decreases by over 60% during summer and early fall. 

PMID- 24454773
TI  - Comparative structural and functional analysis of orthomyxovirus polymerase cap
      snatching domains.
AB  - Orthomyxovirus Influenza A virus (IAV) heterotrimeric polymerase performs
      transcription of viral mRNAs by cap-snatching, which involves generation of
      capped primers by host pre-mRNA binding via the PB2 subunit cap-binding site and
      cleavage 10-13 nucleotides from the 5' cap by the PA subunit endonuclease.
      Thogotoviruses, tick-borne orthomyxoviruses that includes Thogoto (THOV), Dhori
      (DHOV) and Jos (JOSV) viruses, are thought to perform cap-snatching by cleaving
      directly after the cap and thus have no heterogeneous, host-derived sequences at
      the 5' extremity of their mRNAs. Based on recent work identifying the cap-binding
      and endonuclease domains in IAV polymerase, we determined the crystal structures
      of two THOV PB2 domains, the putative cap-binding and the so-called '627-domain',
      and the structures of the putative endonuclease domains (PA-Nter) of THOV and
      DHOV. Despite low sequence similarity, corresponding domains have the same fold
      confirming the overall architectural similarity of orthomyxovirus polymerases.
      However the putative Thogotovirus cap-snatching domains in PA and PB2 have non
      conservative substitutions of key active site residues. Biochemical analysis
      confirms that, unlike the IAV domains, the THOV and DHOV PA-Nter domains do not
      bind divalent cations and have no endonuclease activity and the THOV central PB2
      domain does not bind cap analogues. On the other hand, sequence analysis suggests
      that other, non-influenza, orthomyxoviruses, such as salmon anemia virus
      (isavirus) and Quaranfil virus likely conserve active cap-snatching domains
      correlating with the reported occurrence of heterogeneous, host-derived sequences
      at the 5' end of the mRNAs of these viruses. These results highlight the unusual
      nature of transcription initiation by Thogotoviruses. 

PMID- 24454774
TI  - Proteomic analysis of cellular response induced by multi-walled carbon nanotubes
      exposure in A549 cells.
AB  - The wide application of multi-walled carbon nanotubes (MWCNT) has raised serious
      concerns about their safety on human health and the environment. However, the
      potential harmful effects of MWCNT remain unclear and contradictory. To clarify
      the potentially toxic effects of MWCNT and to elucidate the associated underlying
      mechanisms, the effects of MWCNT on human lung adenocarcinoma A549 cells were
      examined at both the cellular and the protein level. Cytotoxicity and
      genotoxicity were examined, followed by a proteomic analysis (2-DE coupled with
      LC-MS/MS) of the cellular response to MWCNT. Our results demonstrate that MWCNT
      induces cytotoxicity in A549 cells only at relatively high concentrations and
      longer exposure time. Within a relatively low dosage range (30 ug/ml) and short
      time period (24 h), MWCNT treatment does not induce significant cytotoxicity,
      cell cycle changes, apoptosis, or DNA damage. However, at these low doses and
      times, MWCNT treatment causes significant changes in protein expression. A total
      of 106 proteins show altered expression at various time points and dosages, and
      of these, 52 proteins were further identified by MS. Identified proteins are
      involved in several cellular processes including proliferation, stress, and
      cellular skeleton organization. In particular, MWCNT treatment causes increases
      in actin expression. This increase has the potential to contribute to increased
      migration capacity and may be mediated by reactive oxygen species (ROS). 

PMID- 24454775
TI  - Toxicity of functional nano-micro zinc oxide tetrapods: impact of cell culture
      conditions, cellular age and material properties.
AB  - With increasing production and applications of nanostructured zinc oxide, e.g.,
      for biomedical and consumer products, the question of safety is getting more and
      more important. Different morphologies of zinc oxide structures have been
      synthesized and accordingly investigated. In this study, we have particularly
      focused on nano-micro ZnO tetrapods (ZnO-T), because their large scale
      fabrication has been made possible by a newly introduced flame transport
      synthesis approach which will probably lead to several new applications.
      Moreover, ZnO-T provide a completely different morphology then classical
      spherical ZnO nanoparticles. To get a better understanding of parameters that
      affect the interactions between ZnO-T and mammalian cells, and thus their
      biocompatibility, we have examined the impact of cell culture conditions as well
      as of material properties on cytotoxicity. Our results demonstrate that the cell
      density of fibroblasts in culture along with their age, i.e., the number of
      preceding cell divisions, strongly affect the cytotoxic potency of ZnO-T.
      Concerning the material properties, the toxic potency of ZnO-T is found to be
      significantly lower than that of spherical ZnO nanoparticles. Furthermore, the
      morphology of the ZnO-T influenced cellular toxicity in contrast to surface
      charges modified by UV illumination or O2 treatment and to the material age.
      Finally, we have observed that direct contact between tetrapods and cells
      increases their toxicity compared to transwell culture models which allow only an
      indirect effect via released zinc ions. The results reveal several parameters
      that can be of importance for the assessment of ZnO-T toxicity in cell cultures
      and for particle development. 

PMID- 24454776
TI  - Transposon defense by endo-siRNAs, piRNAs and somatic pilRNAs in Drosophila:
      contributions of Loqs-PD and R2D2.
AB  - Transposable elements are a serious threat for genome integrity and their control
      via small RNA mediated silencing pathways is an ancient strategy. The fruit fly
      Drosophila melanogaster has two silencing activities that target transposons:
      endogenous siRNAs (esiRNAs or endo-siRNAs) and Piwi-interacting small RNAs
      (piRNAs). The biogenesis of endo-siRNAs involves the Dicer-2 co-factors Loqs-PD,
      which acts predominantly during processing of dsRNA by Dcr-2, and R2D2, which
      primarily helps to direct siRNAs into the RNA interference effector Ago2.
      Nonetheless, loss of either protein is not sufficient to produce a phenotype
      comparable with a dcr-2 mutation. We provide further deep sequencing evidence
      supporting the notion that R2D2 and Loqs-PD have partially overlapping function.
      Certain transposons display a preference for either dsRBD-protein during
      production or loading; this appeared to correlate neither with overall abundance,
      classification of the transposon or a specific site of genomic origin. The endo
      siRNA biogenesis pathway in germline operates according to the same principles as
      the existing model for the soma, and its impairment does not significantly affect
      piRNAs. Expanding the analysis, we confirmed the occurrence of somatic piRNA-like
      RNAs (pilRNAs) that show a ping-pong signature. We detected expression of the
      Piwi-family protein mRNAs only barely above background, indicating that the
      somatic pilRNAs may arise from a small sub-population of somatic cells that
      express a functional piRNA pathway. 

PMID- 24454777
TI  - Correlations between functional imaging markers derived from PET/CT and diffusion
      weighted MRI in diffuse large B-cell lymphoma and follicular lymphoma.
AB  - OBJECTIVES: To investigate the correlations between functional imaging markers
      derived from positron emission tomography/computed tomography (PET/CT) and
      diffusion-weighted magnetic resonance imaging (DWI) in diffuse large B-cell
      lymphoma (DLBCL) and follicular lymphoma (FL). Further to compare the usefulness
      of these tumor markers in differentiating diagnosis of the two common types of
      Non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: Thirty-four consecutive pre
      therapy adult patients with proven NHL (23 DLBCL and 11 FL) underwent PET/CT and
      MRI examinations and laboratory tests. The maximum standardized uptake value
      (SUV(max)), metabolic tumor volume (MTV), and metabolic tumor burden (MTB) were
      determined from the PET/CT images. DWI was performed in addition to conventional
      MRI sequences using two b values (0 and 800 s/mm(2)). The minimum and mean
      apparent diffusion coefficient (ADC(min) and ADC(mean)) were measured on the
      parametric ADC maps. RESULTS: The SUV(max) correlated inversely with the ADC(min)
      (r =  -0.35, p<0.05). The ADC(min), ADC(mean), serum thymidine kinase (TK), Beta
      2-microglobulin (B2m), lactate dehydrogenase (LD), and C-reactive protein (CRP)
      correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01). The
      SUV(max), TK, LD, and CRP were significantly higher in the DLBCL group than in
      the FL group. Receiver operating characteristic curve analysis showed that they
      were reasonable predictors in differentiating DLBCL from FL. CONCLUSIONS: The
      functional imaging markers determined from PET/CT and DWI are associated, and the
      SUV(max) is superior to the ADC(min) in differentiating DLBCL from FL. All the
      measured serum markers are associated with functional imaging markers. Serum LD,
      TK, and CRP are useful in differentiating DLBCL from FL.

PMID- 24454778
TI  - Childhood adversity accelerates intended reproductive timing in adolescent girls
      without increasing interest in infants.
AB  - Women experiencing greater childhood adversity exhibit faster reproductive
      trajectories. One possible psychological mechanism underlying this phenomenon is
      an increased interest in infants. Interest in infants is thought to be an
      adaptation important for successful rearing as it motivates the acquisition of
      caretaking skills. We investigated the relationships between childhood adversity,
      intended reproductive timing and interest in infants in a sample of English
      adolescent girls. Specifically we sought to investigate the relationship between
      1) childhood adversity and intended reproductive timing; 2) childhood adversity
      and interest in infants; and 3) intended reproductive timing and interest in
      infants. Additionally we explored different methods of measuring interest in
      infants using self-reported fondness for babies, a forced choice adult versus
      infant paper-based preference task and a novel computer based attention task
      using adult and infant stimuli. In total 357 girls aged nine to 14 years
      participated in the study, which took place in schools. Participants completed
      the two interest in infants tasks before moving on to a childhood adversity
      questionnaire. Girls with more childhood adversity reported earlier ideal ages at
      parenthood. We found some evidence that, contrary to our predictions, girls with
      less childhood adversity were more interested in infants. There was no
      relationship between intended reproductive timing and interest in infants. The
      different measurements for interest in infants were only weakly related, if at
      all, highlighting the complexity of measuring this construct. Our findings
      suggest that rather than interest in infants being a mechanism for the effect of
      childhood adversity on early reproductive timing it might instead be an indicator
      of future reproductive strategies. 

PMID- 24454779
TI  - Different stimuli, different spatial codes: a visual map and an auditory rate
      code for oculomotor space in the primate superior colliculus.
AB  - Maps are a mainstay of visual, somatosensory, and motor coding in many species.
      However, auditory maps of space have not been reported in the primate brain.
      Instead, recent studies have suggested that sound location may be encoded via
      broadly responsive neurons whose firing rates vary roughly proportionately with
      sound azimuth. Within frontal space, maps and such rate codes involve different
      response patterns at the level of individual neurons. Maps consist of neurons
      exhibiting circumscribed receptive fields, whereas rate codes involve open-ended
      response patterns that peak in the periphery. This coding format discrepancy
      therefore poses a potential problem for brain regions responsible for
      representing both visual and auditory information. Here, we investigated the
      coding of auditory space in the primate superior colliculus(SC), a structure
      known to contain visual and oculomotor maps for guiding saccades. We report that,
      for visual stimuli, neurons showed circumscribed receptive fields consistent with
      a map, but for auditory stimuli, they had open-ended response patterns consistent
      with a rate or level-of-activity code for location. The discrepant response
      patterns were not segregated into different neural populations but occurred in
      the same neurons. We show that a read-out algorithm in which the site and level
      of SC activity both contribute to the computation of stimulus location is
      successful at evaluating the discrepant visual and auditory codes, and can
      account for subtle but systematic differences in the accuracy of auditory
      compared to visual saccades. This suggests that a given population of neurons can
      use different codes to support appropriate multimodal behavior. 

PMID- 24454780
TI  - Diversity of Prdm9 zinc finger array in wild mice unravels new facets of the
      evolutionary turnover of this coding minisatellite.
AB  - In humans and mice, meiotic recombination events cluster into narrow hotspots
      whose genomic positions are defined by the PRDM9 protein via its DNA binding
      domain constituted of an array of zinc fingers (ZnFs). High polymorphism and
      rapid divergence of the Prdm9 gene ZnF domain appear to involve positive
      selection at DNA-recognition amino-acid positions, but the nature of the
      underlying evolutionary pressures remains a puzzle. Here we explore the
      variability of the Prdm9 ZnF array in wild mice, and uncovered a high allelic
      diversity of both ZnF copy number and identity with the caracterization of 113
      alleles. We analyze features of the diversity of ZnF identity which is mostly due
      to non-synonymous changes at codons -1, 3 and 6 of each ZnF, corresponding to
      amino-acids involved in DNA binding. Using methods adapted to the minisatellite
      structure of the ZnF array, we infer a phylogenetic tree of these alleles. We
      find the sister species Mus spicilegus and M. macedonicus as well as the three
      house mouse (Mus musculus) subspecies to be polyphyletic. However some
      sublineages have expanded independently in Mus musculus musculus and M. m.
      domesticus, the latter further showing phylogeographic substructure. Compared to
      random genomic regions and non-coding minisatellites, none of these patterns
      appears exceptional. In silico prediction of DNA binding sites for each allele,
      overlap of their alignments to the genome and relative coverage of the different
      families of interspersed repeated elements suggest a large diversity between
      PRDM9 variants with a potential for highly divergent distributions of
      recombination events in the genome with little correlation to evolutionary
      distance. By compiling PRDM9 ZnF protein sequences in Primates, Muridae and
      Equids, we find different diversity patterns among the three amino-acids most
      critical for the DNA-recognition function, suggesting different diversification
      timescales. 

PMID- 24454781
TI  - Eicosapentaenoic acid activates RAS/ERK/C/EBPbeta pathway through H-Ras intron 1
      CpG island demethylation in U937 leukemia cells.
AB  - Epigenetic alterations, including aberrant DNA methylation, contribute to tumor
      development and progression. Silencing of tumor suppressor genes may be ascribed
      to promoter DNA hypermethylation, a reversible phenomenon intensely investigated
      as potential therapeutic target. Previously, we demonstrated that
      eicosapentaenoic acid (EPA) exhibits a DNA demethylating action that promotes the
      re-expression of the tumor suppressor gene CCAAT/enhancer-binding protein delta
      (C/EBPdelta). The C/EBPbeta/C/EBPdelta heterodimer formed appears essential for
      the monocyte differentiation commitment. The present study aims to evaluate the
      effect of EPA on RAS/extracellular signal regulated kinases (ERK1/2)/C/EBPbeta
      pathway, known to be induced during the monocyte differentiation program. We
      found that EPA conditioning of U937 leukemia cells activated RAS/ERK/C/EBPbeta
      pathway, increasing the C/EBPbeta and ERK1/2 active phosphorylated forms.
      Transcriptional induction of the upstream activator H-Ras gene resulted in
      increased expression of H-Ras protein in the active pool of non raft membrane
      fraction. H-Ras gene analysis identified an hypermethylated CpG island in intron
      1 that can affect the DNA-protein interaction modifying RNA polymerase II
      (RNAPII) activity. EPA treatment demethylated almost completely this CpG island,
      which was associated with an enrichment of active RNAPII. The increased binding
      of the H-Ras transcriptional regulator p53 to its consensus sequence within the
      intronic CpG island further confirmed the effect of EPA as demethylating agent.
      Our results provide the first evidence that an endogenous polyunsaturated fatty
      acid (PUFA) promotes a DNA demethylation process responsible for the activation
      of RAS/ERK/C/EBPbeta pathway during the monocyte differentiation commitment. The
      new role of EPA as demethylating agent paves the way for studying PUFA action
      when aberrant DNA methylation is involved. 

PMID- 24454782
TI  - 40LoVe and Samba are involved in Xenopus neural development and functionally
      distinct from hnRNP AB.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a large group of
      modular RNA-binding proteins classified according to their conserved domains.
      This modular nature, coupled with a large choice of alternative splice variants
      generates functional diversity. Here, we investigate the biological differences
      between 40LoVe, its splice variant Samba and its pseudoallele hnRNP AB in neural
      development. Loss of function experiments lead to defects in neural development
      with reduction of eye size, which stem primarily from increased apoptosis and
      reduced proliferation in neural tissues. Despite very high homology between
      40LoVe/Samba and hnRNP AB, these proteins display major differences in
      localization, which appear to be in part responsible for functional differences.
      Specifically, we show that the 40Love/Samba carboxy-terminal domain (GRD) enables
      nucleocytoplasmic shuttling behavior. This domain is slightly different in hnRNP
      AB, leading to nuclear-restricted localization. Finally, we show that shuttling
      is required for 40LoVe/Samba function in neural development. 

PMID- 24454783
TI  - Intravascular administration of mannitol for acute kidney injury prevention: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The effects of mannitol administration on acute kidney injury (AKI)
      prevention remain uncertain, as the results from clinical studies were
      conflicting. Due to the lack of strong evidence, the KDIGO Guideline for AKI did
      not propose completely evidence-based recommendations on this issue. METHODS: We
      searched PubMed, EMBASE, clinicaltrials.gov and Cochrane Controlled Trials
      Register. Randomized controlled trials on adult patients at increased risk of AKI
      were considered on the condition that they compared the effects of intravascular
      administration of mannitol plus expansion of intravascular volume with expansion
      of intravascular volume alone. We calculated pooled risk ratios, numbers needed
      to treat and mean differences with 95% confidence intervals for dichotomous data
      and continuous data, respectively. RESULTS: Nine trials involving 626 patients
      were identified. Compared with expansion of intravascular volume alone, mannitol
      infusion for AKI prevention in high-risk patients can not reduce the serum
      creatinine level (MD 1.63, 95% CI -6.02 to 9.28). Subgroup analyses demonstrated
      that serum creatinine level is negatively affected by the use of mannitol in
      patients undergoing an injection of radiocontrast agents (MD 17.90, 95% CI 8.56
      to 27.24). Mannitol administration may reduce the incidence of acute renal
      failure or the need of dialysis in recipients of renal transplantation (RR 0.34,
      95% CI 0.21 to 0.57, NNT 3.03, 95% CI 2.17 to 5.00). But similar effects were not
      found in patients at high AKI risk, without receiving renal transplantation (RR
      0.29, 95% CI 0.01 to 6.60). CONCLUSIONS: Intravascular administration of mannitol
      does not convey additional beneficial effects beyond adequate hydration in the
      patients at increased risk of AKI. For contrast-induced nephropathy, the use of
      mannitol is even detrimental. Further research evaluating the efficiency of
      mannitol infusions in the recipients of renal allograft should be undertaken.

PMID- 24454784
TI  - The impact of sexual abuse in patients undergoing colonoscopy.
AB  - BACKGROUND: Sexual abuse has been linked to strong effects on gastrointestinal
      health. Colonoscopy can provoke intense emotional reactions in patients with a
      sexual abuse history and may lead to avoidance of endoscopic procedures.
      OBJECTIVE: To determine whether care around colonoscopy needs adjustment for
      patients with sexual abuse experience, thereby exploring targets for the
      improvement of care around colonoscopic procedures. METHODS: Questionnaires were
      mailed to patients (n = 1419) from two centers within 11 months after
      colonoscopy. Differences in experience of the colonoscopy between patients with
      and without a sexual abuse history were assessed and patients' views regarding
      physicians' inquiry about sexual abuse and care around endoscopic procedures were
      obtained. RESULTS: A total of 768 questionnaires were analyzed. The prevalence of
      sexual abuse was 3.9% in male and 9.5% in female patients. Patients born in a non
      western country reported more sexual abuse (14.9%) than those born in a western
      country (6.3%; p = 0.008). Discomfort during colonoscopy was indicated on a scale
      from 0 to 10, mean distress score of patients with sexual abuse was 4.8(+/- 3.47)
      compared to 3.5(+/- 3.11) in patients without a sexual abuse history (p = 0.007).
      Abdominal pain was a predictor for higher distress during colonoscopy (beta = 
      0.019 (SE = 0.008); p = 0.02, as well as the number of complaints indicated as
      reason for colonoscopy (beta = 0.738 (SE = 0.276); p = 0.008). Of patients with
      sexual abuse experience, 53.8% believed gastroenterologists should ask about it,
      43.4% said deeper sedation during colonoscopy would diminish the distress.
      CONCLUSIONS: Sexual abuse is prevalent in patients presenting for colonoscopy.
      Patients with a sexual abuse history experience more distress during the
      procedure and indicate that extra attention around and during colonoscopy may
      diminish this distress.

PMID- 24454785
TI  - Fabrication of smart chemical sensors based on transition-doped-semiconductor
      nanostructure materials with u-chips.
AB  - Transition metal doped semiconductor nanostructure materials (Sb2O3 doped ZnO
      microflowers, MFs) are deposited onto tiny u-chip (surface area, ~0.02217 cm(2))
      to fabricate a smart chemical sensor for toxic ethanol in phosphate buffer
      solution (0.1 M PBS). The fabricated chemi-sensor is also exhibited higher
      sensitivity, large-dynamic concentration ranges, long-term stability, and
      improved electrochemical performances towards ethanol. The calibration plot is
      linear (r(2) = 0.9989) over the large ethanol concentration ranges (0.17 mM to
      0.85 M). The sensitivity and detection limit is ~5.845 uAcm(-2)mM(-1) and ~0.11+/
      0.02 mM (signal-to-noise ratio, at a SNR of 3) respectively. Here, doped MFs are
      prepared by a wet-chemical process using reducing agents in alkaline medium,
      which characterized by UV/vis., FT-IR, Raman, X-ray photoelectron spectroscopy
      (XPS), powder X-ray diffraction (XRD), and field-emission scanning electron
      microscopy (FE-SEM) etc. The fabricated ethanol chemical sensor using Sb2O3-ZnO
      MFs is simple, reliable, low-sample volume (<70.0 uL), easy of integration, high
      sensitivity, and excellent stability for the fabrication of efficient I-V sensors
      on MU-chips. 

PMID- 24454786
TI  - Perceived impeding factors for return-to-work after long-term sickness absence
      due to major depressive disorder: a concept mapping approach.
AB  - OBJECTIVE: The purpose of the present study was to explore various stakeholder
      perspectives regarding factors that impede return-to-work (RTW) after long-term
      sickness absence related to major depressive disorder (MDD). METHODS: Concept
      mapping was used to explore employees', supervisors' and occupational physicians'
      perspectives on these impeding factors. RESULTS: Nine perceived themes, grouped
      in three meta-clusters were found that might impede RTW: Person, (personality /
      coping problems, symptoms of depression and comorbid (health) problems, employee
      feels misunderstood, and resuming work too soon), Work (troublesome work
      situation, too little support at work, and too little guidance at work) and
      Healthcare (insufficient mental healthcare and insufficient care from
      occupational physician). All stakeholders regarded personality/coping problems
      and symptoms of depression as the most important impeding theme. In addition,
      supervisors emphasized the importance of mental healthcare underestimating the
      importance of the work environment, while occupational physicians stressed the
      importance of the lack of safety and support in the work environment.
      CONCLUSIONS: In addition to the reduction of symptoms, more attention is needed
      on coping with depressive symptoms and personality problems in the work
      environment support in the work environment and for RTW in mental healthcare, to
      prevent long term sickness absence.

PMID- 24454788
TI  - Economic decisions for others: an exception to loss aversion law.
AB  - In everyday life, people often make decisions on behalf of others. The current
      study investigates whether risk preferences of decision-makers differ when the
      reference point is no longer their own money but somebody else money. Thirty four
      healthy participants performed three different monetary risky choices tasks by
      making decisions for oneself and for another unknown person. Results showed that
      loss aversion bias was significantly reduced when participants were choosing on
      behalf of another person compared to when choosing for themselves. The influence
      of emotions like regret on decision-making may explain these results. We discuss
      the importance of the sense of responsibility embodied in the emotion of regret
      in modulating economic decisions for self but not for others. Moreover, our
      findings are consistent with the Risk-as-feelings hypothesis, suggesting that
      self-other asymmetrical behavior is due to the extent the decision-maker is
      affected by the real and emotional consequences of his/her decision. 

PMID- 24454787
TI  - Do ABO blood group antigens hamper the therapeutic efficacy of mesenchymal
      stromal cells?
AB  - Investigation into predictors for treatment outcome is essential to improve the
      clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We
      therefore studied the possible harmful impact of immunogenic ABO blood groups
      antigens - genetically governed antigenic determinants - at all given steps of
      MSC-therapy, from cell isolation and preparation for clinical use, to final
      recipient outcome. We found that clinical MSCs do not inherently express or
      upregulate ABO blood group antigens after inflammatory challenge or in vitro
      differentiation. Although antigen adsorption from standard culture supplements
      was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB
      plasma (ABP), dependent on antigen concentration and adsorption time. Compared to
      cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP
      elicited stronger blood responses after exposure to blood from healthy O donors
      in vitro, containing high titers of ABO antibodies. Clinical evaluation of
      hematopoietic stem cell transplant (HSCT) recipients found only very low titers
      of anti-A/B agglutination in these strongly immunocompromised patients at the
      time of MSC treatment. Patient analysis revealed a trend for lower clinical
      response in blood group O recipients treated with ABP-exposed MSC products, but
      not with HSA-exposed products. We conclude, that clinical grade MSCs are ABO
      neutral, but the ABP used for washing and infusion of MSCs can contaminate the
      cells with immunogenic ABO substance and should therefore be substituted by non
      immunogenic HSA, particularly when cells are given to immunocompentent
      individuals. 

PMID- 24454789
TI  - Quilt plots: a simple tool for the visualisation of large epidemiological data.
AB  - BACKGROUND: Graphical representation of data is one of the most easily
      comprehended forms of explanation. The current study describes a simple
      visualization tool which may allow greater understanding of medical and
      epidemiological data. METHOD: We propose a simple use of an existing tool for
      visualization of data, known as a ''quilt plot'' (also defined as "heat maps"),
      that provides an alternative to presenting large volumes of data as frequency
      tables [corrected]. Data from the Australian Needle and Syringe Program survey
      are used to illustrate "quilt plots". CONCLUSION: Visualization of large volumes
      of data using "quilt plots" enhances interpretation of medical and
      epidemiological data. Such intuitive presentations are particularly useful for
      the rapid assessment of problems in the data which cannot be readily identified
      by manual review. We recommend that, where possible, "quilt plots" be used along
      with traditional quantitative assessments of the data as an explanatory data
      analysis tool.

PMID- 24454791
TI  - Ecological structure of recent and last glacial mammalian faunas in northern
      Eurasia: the case of Altai-Sayan refugium.
AB  - Pleistocene mammalian communities display unique features which differ from
      present-day faunas. The paleocommunities were characterized by the
      extraordinarily large body size of herbivores and predators and by their unique
      structure consisting of species now inhabiting geographically and ecologically
      distinct natural zones. These features were probably the result of the unique
      environmental conditions of ice age ecosystems. To analyze the ecological
      structure of Last Glacial and Recent mammal communities we classified the species
      into biome and trophic-size categories, using Principal Component analysis. We
      found a marked similarity in ecological structure between Recent eastern Altai
      Sayan mammalian assemblages and comparable Pleistocene faunas. The composition of
      Last Glacial and Recent eastern Altai-Sayan assemblages were characterized by the
      occurrence of large herbivore and predator species associated with steppe, desert
      and alpine biomes. These three modern biomes harbor most of the surviving
      Pleistocene mammals. None of the analyzed Palearctic Last Glacial faunas showed
      affinity to the temperate forest, taiga, or tundra biome. The Eastern part of the
      Altai-Sayan region could be considered a refugium of the Last Glacial-like
      mammalian assemblages. Glacial fauna seems to persist up to present in those
      areas where the forest belt does not separate alpine vegetation from the steppes
      and deserts. 

PMID- 24454790
TI  - Circulating docosahexaenoic acid levels are associated with fetal insulin
      sensitivity.
AB  - BACKGROUND: Arachidonic acid (AA; C20?4 n-6) and docosahexaenoic acid (DHA; C22?6
      n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in
      maintaining pancreatic beta-cell structure and function. Newborns of gestational
      diabetic mothers are more susceptible to the development of type 2 diabetes in
      adulthood. It is not known whether low circulating AA or DHA is involved in
      perinatally "programming" this susceptibility. This study aimed to assess whether
      circulating concentrations of AA, DHA and other fatty acids are associated with
      fetal insulin sensitivity or beta-cell function, and whether low circulating
      concentrations of AA or DHA are involved in compromised fetal insulin sensitivity
      in gestational diabetic pregnancies. METHODS AND PRINCIPAL FINDINGS: In a
      prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord
      plasma fatty acids were assessed in relation to surrogate indicators of fetal
      insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin
      concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother
      newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were
      lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic
      pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood
      sampling, lower cord plasma DHA levels were associated with lower fetal insulin
      sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher
      proinsulin concentration, r = -0.37, P <0.0001). The associations remained after
      adjustment for maternal and newborn characteristics. Cord plasma saturated fatty
      acids C18?0 and C20?0 were negatively correlated with fetal insulin sensitivity,
      but their levels were not different between gestational diabetic and non-diabetic
      pregnancies. Cord plasma AA levels were not correlated with fetal insulin
      sensitivity. CONCLUSION: Low circulating DHA levels are associated with
      compromised fetal insulin sensitivity, and may be involved in perinatally
      "programming" the susceptibility to type 2 diabetes in the offspring of
      gestational diabetic mothers.

PMID- 24454792
TI  - The multicenter study of a new assay for simultaneous detection of multiple anti
      aminoacyl-tRNA synthetases in myositis and interstitial pneumonia.
AB  - OBJECTIVE: Autoantibodies to aminoacyl-tRNA synthetases (ARSs) are useful in the
      diagnosis of idiopathic inflammatory myopathy (IIM) with interstitial pneumonia
      (IP). We developed an enzyme-linked immunosorbent assay (ELISA) system using a
      mixture of recombinant ARS antigens and tested its utility in a multicenter
      study. METHODS: We prepared six recombinant ARSs: GST-Jo-1, His-PL-12, His-EJ and
      GST-KS expressed in Escherichia coli, and His-PL-7 and His-OJ expressed in Hi-5
      cells. After confirming their antigenic activity, with the exception of His-OJ,
      we developed our ELISA system in which the five recombinant ARSs (without His-OJ)
      were mixed. Efficiency was confirmed using the sera from 526 Japanese patients
      with connective tissue disease (CTD) (IIM n = 250, systemic lupus erythematosus n
      = 91, systemic sclerosis n = 70, rheumatoid arthritis n = 75, Sjogren's syndrome
      n = 27 and other diseases n = 13), 168 with idiopathic interstitial pneumonia
      (IIP) and 30 healthy controls collected from eight institutes. IIPs were
      classified into two groups; idiopathic pulmonary fibrosis (IPF) (n = 38) and non
      IPF (n = 130). RESULTS were compared with those of RNA immunoprecipitation.
      RESULTS: Sensitivity and specificity of the ELISA were 97.1% and 99.8%,
      respectively when compared with the RNA immunoprecipitation assay. Anti-ARS
      antibodies were detected in 30.8% of IIM, 2.5% of non-myositis CTD, and 10.7% of
      IIP (5.3% of IPF and 12.3% of non-IPF). Anti-ARS-positive non-IPF patients were
      younger and more frequently treated with glucocorticoids and/or
      immunosuppressants than anti-ARS-negative patients. CONCLUSION: A newly
      established ELISA detected anti-ARS antibodies as efficiently as RNA
      immunoprecipitation. This system will enable easier and wider use in the
      detection of anti-ARS antibodies in patients with IIM and IIP.

PMID- 24454793
TI  - Bacteria and fungi respond differently to multifactorial climate change in a
      temperate heathland, traced with 13C-glycine and FACE CO2.
AB  - It is vital to understand responses of soil microorganisms to predicted climate
      changes, as these directly control soil carbon (C) dynamics. The rate of turnover
      of soil organic carbon is mediated by soil microorganisms whose activity may be
      affected by climate change. After one year of multifactorial climate change
      treatments, at an undisturbed temperate heathland, soil microbial community
      dynamics were investigated by injection of a very small concentration (5.12 ug C
      g(-1) soil) of (13)C-labeled glycine ((13)C2, 99 atom %) to soils in situ. Plots
      were treated with elevated temperature (+1 degrees C, T), summer drought (D) and
      elevated atmospheric carbon dioxide (510 ppm [CO2]), as well as combined
      treatments (TD, TCO2, DCO2 and TDCO2). The (13)C enrichment of respired CO2 and
      of phospholipid fatty acids (PLFAs) was determined after 24 h. (13)C-glycine
      incorporation into the biomarker PLFAs for specific microbial groups (Gram
      positive bacteria, Gram negative bacteria, actinobacteria and fungi) was
      quantified using gas chromatography-combustion-stable isotope ratio mass
      spectrometry (GC-C-IRMS). Gram positive bacteria opportunistically utilized the
      freshly added glycine substrate, i.e. incorporated (13)C in all treatments,
      whereas fungi had minor or no glycine derived (13)C-enrichment, hence slowly
      reacting to a new substrate. The effects of elevated CO2 did suggest increased
      direct incorporation of glycine in microbial biomass, in particular in G(+)
      bacteria, in an ecosystem subjected to elevated CO2. Warming decreased the
      concentration of PLFAs in general. The FACE CO2 was (13)C-depleted (delta(13)C =
      12.20/00) compared to ambient (delta(13)C = ~-80/00), and this enabled
      observation of the integrated longer term responses of soil microorganisms to the
      FACE over one year. All together, the bacterial (and not fungal) utilization of
      glycine indicates substrate preference and resource partitioning in the microbial
      community, and therefore suggests a diversified response pattern to future
      changes in substrate availability and climatic factors.

PMID- 24454794
TI  - The effect of recombinant human iduronate-2-sulfatase (Idursulfase) on growth in
      young patients with mucopolysaccharidosis type II.
AB  - Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked,
      recessive, lysosomal storage disorder caused by deficiency of iduronate-2
      sulfatase. Early bone involvement leads to decreased growth velocity and short
      stature in nearly all patients. Our analysis aimed to investigate the effects of
      enzyme replacement therapy (ERT) with idursulfase (Elaprase) on growth in young
      patients with mucopolysaccharidosis type II. Analysis of longitudinal
      anthropometric data of MPS II patients (group 1, n = 13) who started ERT before 6
      years of age (range from 3 months to 6 years, mean 3.6 years, median 4 years) was
      performed and then compared with retrospective analysis of data for MPS II
      patients naive to ERT (group 2, n = 50). Patients in group 1 received intravenous
      idursulfase at a standard dose of 0.58 mg/kg weekly for 52-288 weeks. The course
      of average growth curve for group 1 was very similar to growth pattern in group
      2. The average value of body height in subsequent years in group 1 was a little
      greater than in group 2, however, the difference was not statistically
      significant. In studied patients with MPS II, idursulfase did not appear to alter
      the growth patterns. 

PMID- 24454795
TI  - Impact of cigarette smoking on outcome of hepatocellular carcinoma after surgery
      in patients with hepatitis B.
AB  - BACKGROUND AND OBJECTIVES: Cigarette smoking is a potential risk factor for
      hepatocellular carcinoma (HCC) initiation, partially through interaction with
      hepatitis B virus (HBV). We examined the hypothesis that cigarette smoking might
      be associated with HBV-related HCC recurrence and patient survival after curative
      surgery. PATIENTS AND METHODS: Data of 302 patients with HBV infection who had
      undergone curative resection for HCC were prospectively collected from 2008 to
      2011. Smoking status and smoking quantity (pack-years, PY) were asked at
      admission. Factors affecting recurrence-free survival (RFS) were examined. RFS
      and liver-specific mortality (LSM) stratified by risk factors were compared with
      log-rank test. RESULTS: 109 were current smokers. Current smokers were not
      different from non-smokers in tumor burden and surgical procedure. Univariate and
      multivariate analysis identified that heavy smoking (PY >= 20) was the most
      significant factor associated with HBV-related HCC recurrence after curative
      surgical resection (p = 0.001), followed by anti-HBV treatment (p<0.01), current
      smoking (p = 0.028), surgical margin <1 cm (p = 0.048) and blood transfusion >600
      ml (p = 0.028). The median RFS in non-smokers, ex-smokers and current smokers was
      34 months, 24 months and 26 months, respectively (p = 0.033). Current smokers had
      significantly worse RFS rate and increased 5-year cumulative LSM than non-smokers
      (p = 0.024, and p<0.001, respectively). Heavy smokers had significantly worse RFS
      than non- and light smokers (0<PY<20) (p<0.001, respectively) and higher
      cumulative LSM than non-smokers and light smokers (p = 0.003 and 0.001,
      respectively). Furthermore, in current smokers, continuing smoking
      postoperatively was strongly associated with poorer RFS and higher LSM than those
      who quit smoking postoperatively (p = 0.016 and p = 0.003, respectively).
      CONCLUSIONS: Smoking history and quantity appears to be risk factors for HBV
      related HCC recurrence and LSM of patients after surgery. For smokers, continued
      smoking postoperatively might accelerate tumor recurrence and patient death.
      Therefore, smoking abstinence should be strongly recommended to patients pre- and
      postoperatively.

PMID- 24454796
TI  - Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the
      immune synapse.
AB  - Actin depolymerizing factor-homology (ADF-H) family proteins regulate actin
      filament dynamics at multiple cellular locations. Herein, we have investigated
      the function of the ADF-H family member coactosin-like 1 (COTL1) in the
      regulation of actin dynamics at the T cell immune synapse (IS). We initially
      identified COTL1 in a genetic screen to identify novel regulators of T cell
      activation, and subsequently found that it associates with F-actin and localizes
      at the IS in response to TCR+CD28 stimulation. Live cell microscopy showed that
      depletion of COTL1 protein impaired T cell spreading in response to TCR ligation
      and abrogated lamellipodial protrusion at the T cell - B cell contact site,
      producing only a band of F-actin. Significantly, re-expression of wild type
      COTL1, but not a mutant deficient in F-actin binding could rescue these defects.
      In addition, COTL1 depletion reduced T cell migration. In vitro studies showed
      that COTL1 and cofilin compete with each other for binding to F-actin, and COTL1
      protects F-actin from cofilin-mediated depolymerization. While depletion of
      cofilin enhanced F-actin assembly and lamellipodial protrusion at the IS,
      concurrent depletion of both COTL1 and cofilin restored lamellipodia formation.
      Taken together, our results suggest that COTL1 regulates lamellipodia dynamics in
      part by protecting F-actin from cofilin-mediated disassembly. 

PMID- 24454797
TI  - A new PCR-based method shows that blue crabs (Callinectes sapidus (Rathbun))
      consume winter flounder (Pseudopleuronectes americanus (Walbaum)).
AB  - Winter flounder (Pseudopleuronectes americanus) once supported robust commercial
      and recreational fisheries in the New York (USA) region, but since the 1990s
      populations have been in decline. Available data show that settlement of young-of
      the-year winter flounder has not declined as sharply as adult abundance,
      suggesting that juveniles are experiencing higher mortality following settlement.
      The recent increase of blue crab (Callinectes sapidus) abundance in the New York
      region raises the possibility that new sources of predation may be contributing
      to juvenile winter flounder mortality. To investigate this possibility we
      developed and validated a method to specifically detect winter flounder
      mitochondrial control region DNA sequences in the gut contents of blue crabs. A
      survey of 55 crabs collected from Shinnecock Bay (along the south shore of Long
      Island, New York) in July, August, and September of 2011 showed that 12 of 42
      blue crabs (28.6%) from which PCR-amplifiable DNA was recovered had consumed
      winter flounder in the wild, empirically supporting the trophic link between
      these species that has been widely speculated to exist. This technique overcomes
      difficulties with visual identification of the often unrecognizable gut contents
      of decapod crustaceans, and modifications of this approach offer valuable tools
      to more broadly address their feeding habits on a wide variety of species. 

PMID- 24454798
TI  - The predictive but not prognostic value of MGMT promoter methylation status in
      elderly glioblastoma patients: a meta-analysis.
AB  - BACKGROUND: The clinical implication of O6-methylguanine-DNA methyltransferase
      (MGMT) promoter status is ill-defined in elderly glioblastoma patients. Here we
      report a meta-analysis to seek valid evidence for its clinical relevance in this
      subpopulation. METHODS: Literature were searched and reviewed in a systematic
      manner using the PubMed, EMBASE and Cochrane databases. Studies investigating the
      association between MGMT promoter status and survival data of elderly patients
      (>=65 years) were eligible for inclusion. RESULTS: Totally 16 studies were
      identified, with 13 studies included in the final analyses. The aggregate
      proportion of MGMT promoter methylation in elderly patients was 47% (95%
      confidence interval [CI]: 42-52%), which was similar to the value for younger
      patients. The analyses showed differential effects of MGMT status on overall
      survival (OS) of elderly patients according to assigned treatments: methylated
      vs. unmethylated: (1) temozolomide (TMZ)-containing therapies: hazard ratio [HR]
      0.49, 95% CI 0.41-0.58; (2) TMZ-free therapies: HR 0.97, 95% CI 0.77-1.21. More
      importantly, a useful predictive value was observed by an interaction analysis:
      TMZ-containing therapies vs. RT alone: (1) methylated tumors: HR 0.48, 95% CI
      0.36-0.65; (2) unmethylated tumors: HR 1.14; 95% CI 0.90-1.44. CONCLUSION: The
      meta-analysis reports an age-independent presence of MGMT promoter methylation.
      More importantly, the study encouraged routine testing of MGMT promoter status
      especially in elderly glioblastoma patients by indicating a direct linkage
      between biomarker test and individual treatment decision. Future studies are
      needed to justify the mandatory testing in younger patients.

PMID- 24454799
TI  - Diversity of global rice markets and the science required for consumer-targeted
      rice breeding.
AB  - With the ever-increasing global demand for high quality rice in both local
      production regions and with Western consumers, we have a strong desire to
      understand better the importance of the different traits that make up the quality
      of the rice grain and obtain a full picture of rice quality demographics. Rice is
      by no means a 'one size fits all' crop. Regional preferences are not only
      striking, they drive the market and hence are of major economic importance in any
      rice breeding / improvement strategy. In this analysis, we have engaged local
      experts across the world to perform a full assessment of all the major rice
      quality trait characteristics and importantly, to determine how these are
      combined in the most preferred varieties for each of their regions. Physical as
      well as biochemical characteristics have been monitored and this has resulted in
      the identification of no less than 18 quality trait combinations. This complexity
      immediately reveals the extent of the specificity of consumer preference.
      Nevertheless, further assessment of these combinations at the variety level
      reveals that several groups still comprise varieties which consumers can readily
      identify as being different. This emphasises the shortcomings in the current
      tools we have available to assess rice quality and raises the issue of how we
      might correct for this in the future. Only with additional tools and research
      will we be able to define directed strategies for rice breeding which are able to
      combine important agronomic features with the demands of local consumers for
      specific quality attributes and hence, design new, improved crop varieties which
      will be awarded success in the global market. 

PMID- 24454800
TI  - Reversal effect of ST6GAL 1 on multidrug resistance in human leukemia by
      regulating the PI3K/Akt pathway and the expression of P-gp and MRP1.
AB  - beta-Galactoside alpha2, 6-sialyltransferse gene (ST6GAL) family has two members,
      which encode corresponding enzymes ST6Gal I and ST6Gal II. The present atudy was
      to investigate whether and how ST6GAL family involved in multidrug resistance
      (MDR) in human leukemia cell lines and bone marrow mononuclear cells (BMMC) of
      leukemia patients. Real-time PCR showed a high expression level of ST6GAL1 gene
      in both MDR cells and BMMCs (*P<0.05). Alternation of ST6GAL1 levels had a
      significant impact on drug-resistant phenotype changing of K562 and K562/ADR
      cells both in vitro and in vivo. However, no significant changes were observed of
      ST6GAL2 gene. Further data revealed that manipulation of ST6GAL1 modulated the
      activity of phosphoinositide 3 kinase (PI3K)/Akt signaling and consequently
      regulated the expression of P-glycoprotein (P-gp, *P<0.05) and multidrug
      resistance related protein 1 (MRP1, *P<0.05), which are both known to be
      associated with MDR. Therefore we postulate that ST6GAL1 is responsible for the
      development of MDR in human leukemia cells probably through medicating the
      activity of PI3K/Akt signaling and the expression of P-gp and MRP1.

PMID- 24454801
TI  - Background synaptic activity in rat entorhinal cortex shows a progressively
      greater dominance of inhibition over excitation from deep to superficial layers.
AB  - The entorhinal cortex (EC) controls hippocampal input and output, playing major
      roles in memory and spatial navigation. Different layers of the EC subserve
      different functions and a number of studies have compared properties of neurones
      across layers. We have studied synaptic inhibition and excitation in EC neurones,
      and we have previously compared spontaneous synaptic release of glutamate and
      GABA using patch clamp recordings of synaptic currents in principal neurones of
      layers II (L2) and V (L5). Here, we add comparative studies in layer III (L3).
      Such studies essentially look at neuronal activity from a presynaptic viewpoint.
      To correlate this with the postsynaptic consequences of spontaneous transmitter
      release, we have determined global postsynaptic conductances mediated by the two
      transmitters, using a method to estimate conductances from membrane potential
      fluctuations. We have previously presented some of this data for L3 and now
      extend to L2 and L5. Inhibition dominates excitation in all layers but the ratio
      follows a clear rank order (highest to lowest) of L2>L3>L5. The variance of the
      background conductances was markedly higher for excitation and inhibition in L2
      compared to L3 or L5. We also show that induction of synchronized network
      epileptiform activity by blockade of GABA inhibition reveals a relative
      reluctance of L2 to participate in such activity. This was associated with
      maintenance of a dominant background inhibition in L2, whereas in L3 and L5 the
      absolute level of inhibition fell below that of excitation, coincident with the
      appearance of synchronized discharges. Further experiments identified potential
      roles for competition for bicuculline by ambient GABA at the GABAA receptor, and
      strychnine-sensitive glycine receptors in residual inhibition in L2. We discuss
      our results in terms of control of excitability in neuronal subpopulations of EC
      neurones and what these may suggest for their functional roles. 

PMID- 24454802
TI  - High rates of gene flow by pollen and seed in oak populations across Europe.
AB  - Gene flow is a key factor in the evolution of species, influencing effective
      population size, hybridisation and local adaptation. We analysed local gene flow
      in eight stands of white oak (mostly Quercus petraea and Q. robur, but also Q.
      pubescens and Q. faginea) distributed across Europe. Adult trees within a given
      area in each stand were exhaustively sampled (range [239, 754], mean 423),
      mapped, and acorns were collected ([17,147], 51) from several mother trees ([3],
      [47], 23). Seedlings ([65,387], 178) were harvested and geo-referenced in six of
      the eight stands. Genetic information was obtained from screening distinct
      molecular markers spread across the genome, genotyping each tree, acorn or
      seedling. All samples were thus genotyped at 5-8 nuclear microsatellite loci.
      Fathers/parents were assigned to acorns and seedlings using likelihood methods.
      Mating success of male and female parents, pollen and seed dispersal curves, and
      also hybridisation rates were estimated in each stand and compared on a
      continental scale. On average, the percentage of the wind-borne pollen from
      outside the stand was 60%, with large variation among stands (21-88%). Mean seed
      immigration into the stand was 40%, a high value for oaks that are generally
      considered to have limited seed dispersal. However, this estimate varied greatly
      among stands (20-66%). Gene flow was mostly intraspecific, with large variation,
      as some trees and stands showed particularly high rates of hybridisation. Our
      results show that mating success was unevenly distributed among trees. The high
      levels of gene flow suggest that geographically remote oak stands are unlikely to
      be genetically isolated, questioning the static definition of gene reserves and
      seed stands. 

PMID- 24454803
TI  - Comprehensive genetic analysis of early host body reactions to the bioactive and
      bio-inert porous scaffolds.
AB  - To design scaffolds for tissue regeneration, details of the host body reaction to
      the scaffolds must be studied. Host body reactions have been investigated mainly
      by immunohistological observations for a long time. Despite of recent dramatic
      development in genetic analysis technologies, genetically comprehensive changes
      in host body reactions are hardly studied. There is no information about host
      body reactions that can predict successful tissue regeneration in the future. In
      the present study, porous polyethylene scaffolds were coated with bioactive
      collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl
      methacrylate) (PMB) and were implanted subcutaneously and compared the host body
      reaction to those substrates by normalizing the result using control non-coat
      polyethylene scaffold. The comprehensive analyses of early host body reactions to
      the scaffolds were carried out using a DNA microarray assay. Within numerous
      genes which were expressed differently among these scaffolds, particular genes
      related to inflammation, wound healing, and angiogenesis were focused upon.
      Interleukin (IL)-1beta and IL-10 are important cytokines in tissue responses to
      biomaterials because IL-1beta promotes both inflammation and wound healing and IL
      10 suppresses both of them. IL-1beta was up-regulated in the collagen-coated
      scaffold. Collagen-specifically up-regulated genes contained both M1- and M2
      macrophage-related genes. Marked vessel formation in the collagen-coated scaffold
      was occurred in accordance with the up-regulation of many angiogenesis-inducible
      factors. The DNA microarray assay provided global information regarding the host
      body reaction. Interestingly, several up-regulated genes were detected even on
      the very bio-inert PMB-coated surfaces and those genes include inflammation
      suppressive and wound healing-suppressive IL-10, suggesting that not only active
      tissue response but also the inert response may relates to these genetic
      regulations. 

PMID- 24454804
TI  - Quality control methods in accelerometer data processing: identifying extreme
      counts.
AB  - BACKGROUND: Accelerometers are designed to measure plausible human activity,
      however extremely high count values (EHCV) have been recorded in large-scale
      studies. Using population data, we develop methodological principles for
      establishing an EHCV threshold, propose a threshold to define EHCV in the
      ActiGraph GT1M, determine occurrences of EHCV in a large-scale study, identify
      device-specific error values, and investigate the influence of varying EHCV
      thresholds on daily vigorous PA (VPA). METHODS: We estimated quantiles to analyse
      the distribution of all accelerometer positive count values obtained from 9005
      seven-year old children participating in the UK Millennium Cohort Study. A
      threshold to identify EHCV was derived by differentiating the quantile function.
      Data were screened for device-specific error count values and EHCV, and a
      sensitivity analysis conducted to compare daily VPA estimates using three
      approaches to accounting for EHCV. RESULTS: Using our proposed threshold of >=
      11,715 counts/minute to identify EHCV, we found that only 0.7% of all non-zero
      counts measured in MCS children were EHCV; in 99.7% of these children, EHCV
      comprised < 1% of total non-zero counts. Only 11 MCS children (0.12% of sample)
      returned accelerometers that contained negative counts; out of 237 such values,
      211 counts were equal to -32,768 in one child. The medians of daily minutes spent
      in VPA obtained without excluding EHCV, and when using a higher threshold
      (>=19,442 counts/minute) were, respectively, 6.2% and 4.6% higher than when using
      our threshold (6.5 minutes; p<0.0001). CONCLUSIONS: Quality control processes
      should be undertaken during accelerometer fieldwork and prior to analysing data
      to identify monitors recording error values and EHCV. The proposed threshold will
      improve the validity of VPA estimates in children's studies using the ActiGraph
      GT1M by ensuring only plausible data are analysed. These methods can be applied
      to define appropriate EHCV thresholds for different accelerometer models.

PMID- 24454805
TI  - DL-beta-aminobutyric acid-induced resistance in soybean against Aphis glycines
      Matsumura (Hemiptera: Aphididae).
AB  - Priming can improve plant innate capability to deal with the stresses caused by
      both biotic and abiotic factors. In this study, the effect of DL-beta-amino-n
      butyric acid (BABA) against Aphis glycines Matsumura, the soybean aphid (SA) was
      evaluated. We found that 25 mM BABA as a root drench had minimal adverse impact
      on plant growth and also efficiently protected soybean from SA infestation. In
      both choice and non-choice tests, SA number was significantly decreased to a low
      level in soybean seedlings drenched with 25 mM BABA compared to the control
      counterparts. BABA treatment resulted in a significant increase in the activities
      of several defense enzymes, such as phenylalanine ammonia-lyase (PAL), peroxidase
      (POX), polyphenol oxidase (PPO), chitinase (CHI), and beta-1, 3-glucanase (GLU)
      in soybean seedlings attacked by aphid. Meanwhile, the induction of 15 defense
      related genes by aphid, such as AOS, CHS, MMP2, NPR1-1, NPR1-2, and PR genes,
      were significantly augmented in BABA-treated soybean seedlings. Our study suggest
      that BABA application is a promising way to enhance soybean resistance against
      SA. 

PMID- 24454806
TI  - Role of caveolin-1 in atrial fibrillation as an anti-fibrotic signaling molecule
      in human atrial fibroblasts.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the
      general population; yet, the precise mechanisms resulting in AF are not fully
      understood. Caveolin-1 (Cav-1), the principal structural component of caveolae
      organelles in cardiac fibroblasts, is involved in several cardiovascular
      conditions; however, the study on its function in atrium, in particular, in AF,
      is still lacking. This report examines the hypothesis that Cav-1 confers an anti
      AF effect by mediating atrial structural remodeling through its anti-fibrotic
      action. We evaluated the expression of Cav-1, transforming growth factor-beta1
      (TGF-beta1), and fibrosis in atrial specimens of 13 patients with AF and 10
      subjects with sinus rhythm, and found that the expression of Cav-1 was
      significantly downregulated, whereas TGF-beta1 level, collagens I/III contents
      and atrial fibrosis were markedly increased, in AF. Western blot analysis
      demonstrated that treatment of human atrial fibroblasts (HAFs) with TGF-beta1
      resulted in a concentration- and time-dependent repression of Cav-1.
      Downregulation of Cav-1 with siRNA increased the TGF-beta1-induced activation of
      Smad signal pathway and collagens production in HAFs. Furthermore, incubation of
      HAFs with the peptides derived from Cav-1 to achieve Cav-1 gain-of-function
      abolished the TGF-beta1-induced production of collagens I/III and decreases of
      MMP-2/-9 expression. Therefore it was concluded that Cav-1 is an important anti
      AF signaling mediator by conferring its anti-fibrotic effects in atrium. 

PMID- 24454807
TI  - Body mass index and risk of pancreatic cancer in a Chinese population.
AB  - Few studies have examined the association between body mass index (BMI: kg/m(2))
      and pancreatic cancer risk in Asian populations. We examined this relationship in
      51,251 Chinese men and women aged 45-74 who enrolled between 1993 and 1998 in the
      population based, prospective Singapore Chinese Health Study. Data were collected
      through in-person interviews. By December 31, 2011, 194 cohort participants had
      developed pancreatic cancer. A Cox proportional hazards model was used to
      estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). We
      hypothesized the association between BMI and pancreatic cancer risk may vary by
      smoking status (ever v. never) and there was evidence for this as the interaction
      between BMI and smoking status was significant (p = 0.018). Among ever smokers,
      being classified as underweight (BMI <18.5 kg/m(2)), was associated with a
      significantly elevated risk of pancreatic cancer relative to smokers with a BMI
      of 21.5-24.4 kg/m(2) (HR = 1.99, 95% CI  =  1.03-3.84). This association was
      strengthened after exclusion of the first three years of follow-up time. Among
      never smokers, there was no association between BMI and pancreatic cancer risk.
      However, after excluding pancreatic cancer cases and person-years in the first
      three years of follow-up, never smokers with a BMI >= 27.5 kg/m(2) showed a
      suggestive increased risk of pancreatic cancer relative to never smokers with a
      BMI of 21.5-24.4 kg/m(2) (HR  =  1.75, 95% CI  =  0.93-3.3). In conclusion,
      Singaporean Chinese who were underweight with a history of smoking had an
      increased risk of developing pancreatic cancer, whereas there was no significant
      association between BMI and pancreatic cancer in never smokers.

PMID- 24454808
TI  - Molecular epidemiology of HIV-1 in Panama: origin of non-B subtypes in samples
      collected from 2007 to 2013.
AB  - Phylogenetic studies have suggested that the HIV-1 epidemic in the Americas is
      mainly dominated by HIV subtype B. However, countries of South America and the
      Caribbean have recently reported changes in their circulating HIV-1 genetic
      profiles. The aim of this study was to characterize the molecular profile of the
      HIV-1 epidemic in Panama by the analysis of 655 polymerase gene (pol) sequences
      that were obtained from HIV-infected Panamanians diagnosed between 1987 and 2013.
      Blood samples were collected from recently infected, antiretroviral drug-naive
      and treatment-experienced subjects since mid-2007 to 2013. Viral RNA from plasma
      was extracted and sequences of HIV protease and reverse transcriptase genes were
      obtained. Bootscanning and phylogenetic methods were used for HIV subtyping and
      to trace the putative origin of non-B subtype strains. Our results showed that
      HIV-1 infections in Panama are dominated by subtype B (98.9%). The remaining 1.1%
      is represented by a diverse collection of recombinant variants including: three
      URFs_BC, one CRF20_BG, and one CRF28/29_BF, in addition to one subtype F1 and one
      subtype C, none of which were previously reported in Panama. The non-B subtype
      variants detected in Panama were probably introduced from Brazil (subtype F1 and
      CRF28/29_BF), Cuba (CRF20_BG), Dominican Republic (URFs_BC) and India (subtype
      C). Panama is the geographical vertex that connects the North with South America
      and the Caribbean through trade and cultural relations, which may explain the
      observed introductions of non-B subtype HIV-1 variants from both the Caribbean
      and South America into this Central American country. 

PMID- 24454809
TI  - Osx-Cre targets multiple cell types besides osteoblast lineage in postnatal mice.
AB  - Osterix (Osx or Sp7) is a zinc-finger-family transcriptional factor essential for
      osteoblast differentiation in mammals. The Osx-Cre mouse line (also known as Osx1
      GFP::Cre) expresses GFP::Cre fusion protein from a BAC transgene containing the
      Osx regulatory sequence. The mouse strain was initially characterized during
      embryogenesis, and found to target mainly osteoblast-lineage cells. Because the
      strain has been increasingly used in postnatal studies, it is important to
      evaluate its targeting specificity in mice after birth. By crossing the Osx-Cre
      mouse with the R26-mT/mG reporter line and analyzing the progenies at two months
      of age, we find that Osx-Cre targets not only osteoblasts, osteocytes and
      hypertrophic chondrocytes as expected, but also stromal cells, adipocytes and
      perivascular cells in the bone marrow. The targeting of adipocytes and
      perivascular cells appears to be specific to those residing within the bone
      marrow, as the same cell types elsewhere are not targeted. Beyond the skeleton,
      Osx-Cre also targets the olfactory glomerular cells, and a subset of the gastric
      and intestinal epithelium. Thus, potential contributions from the non-osteoblast
      lineage cells should be considered when Osx-Cre is used to study gene functions
      in postnatal mice. 

PMID- 24454810
TI  - Local adaptation at the transcriptome level in brown trout: evidence from early
      life history temperature genomic reaction norms.
AB  - Local adaptation and its underlying molecular basis has long been a key focus in
      evolutionary biology. There has recently been increased interest in the
      evolutionary role of plasticity and the molecular mechanisms underlying local
      adaptation. Using transcriptome analysis, we assessed differences in gene
      expression profiles for three brown trout (Salmo trutta) populations, one
      resident and two anadromous, experiencing different temperature regimes in the
      wild. The study was based on an F2 generation raised in a common garden setting.
      A previous study of the F1 generation revealed different reaction norms and
      significantly higher QST than FST among populations for two early life-history
      traits. In the present study we investigated if genomic reaction norm patterns
      were also present at the transcriptome level. Eggs from the three populations
      were incubated at two temperatures (5 and 8 degrees C) representing conditions
      encountered in the local environments. Global gene expression for fry at the
      stage of first feeding was analysed using a 32k cDNA microarray. The results
      revealed differences in gene expression between populations and temperatures and
      population * temperature interactions, the latter indicating locally adapted
      reaction norms. Moreover, the reaction norms paralleled those observed previously
      at early life-history traits. We identified 90 cDNA clones among the genes with
      an interaction effect that were differently expressed between the ecologically
      divergent populations. These included genes involved in immune- and stress
      response. We observed less plasticity in the resident as compared to the
      anadromous populations, possibly reflecting that the degree of environmental
      heterogeneity encountered by individuals throughout their life cycle will select
      for variable level of phenotypic plasticity at the transcriptome level. Our study
      demonstrates the usefulness of transcriptome approaches to identify genes with
      different temperature reaction norms. The responses observed suggest that
      populations may vary in their susceptibility to climate change. 

PMID- 24454811
TI  - Silencing of CHD5 gene by promoter methylation in leukemia.
AB  - Chromodomain helicase DNA binding protein 5 (CHD5) was previously proposed to
      function as a potent tumor suppressor by acting as a master regulator of a tumor
      suppressive network. CHD5 is down-regulated in several cancers, including
      leukemia and is responsible for tumor generation and progression. However, the
      mechanism of CHD5 down-regulation in leukemia is largely unknown. In this study,
      quantitative reverse-transcriptase polymerase chain reaction and western blotting
      analyses revealed that CHD5 was down-regulated in human leukemia cell lines and
      samples. Luciferase reporter assays showed that most of the baseline regulatory
      activity was localized from 500 to 200 bp upstream of the transcription start
      site. Bisulfite DNA sequencing of the identified regulatory element revealed that
      the CHD5 promoter was hypermethylated in human leukemia cells and samples. Thus,
      CHD5 expression was inversely correlated with promoter DNA methylation in these
      samples. Treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine
      (DAC) activates CHD5 expression in human leukemia cell lines. In vitro luciferase
      reporter assays demonstrated that methylation of the CHD5 promoter repressed its
      promoter activity. Furthermore, a chromatin immunoprecipitation assay combined
      with qualitative PCR identified activating protein 2 (AP2) as a potential
      transcription factor involved in CHD5 expression and indicated that treatment
      with DAC increases the recruitment of AP2 to the CHD5 promoter. In vitro
      transcription-factor activity studies showed that AP2 over-expression was able to
      activate CHD5 promoter activity. Our findings indicate that repression of CHD5
      gene expression in human leukemia is mediated in part by DNA methylation of its
      promoter. 

PMID- 24454812
TI  - Differential compartmentalization of HIV-targeting immune cells in inner and
      outer foreskin tissue.
AB  - Ex vivo foreskin models have demonstrated that inner foreskin is more susceptible
      to HIV-1 infection than outer foreskin. In the present study we characterized the
      compartition of HIV-1 target cells and quantified these cells in the epidermis
      and dermis of inner and outer foreskins using immunohistochemistry and flow
      cytometry. Our data showed that the epidermis of the inner foreskin was more
      enriched with CD4(+) T cells and Langerhans cells (LCs), with the co-expression
      of CCR5 and alpha4beta7 receptors, than the outer foreskin. Interestingly, the
      vast majority of CD4(+) T cells and LCs expressed CCR5, but not CXCR4, indicating
      that the inner foreskin might capture and transmit R5-tropic HIV strains more
      efficiently. In addition, lymphoid aggregates, composed of T cells, macrophages
      and dendritic cells (DCs) in the dermis, were closer to the epithelial surface in
      the inner foreskin than in the outer foreskin. As dendritic cells are able to
      capture and pass HIV particles to susceptible target cells, HIV may be able to
      more efficiently infect the inner foreskin by hijacking the augmented immune
      communication pathways in this tissue. After the inoculation of HIV-1 particles
      in a foreskin explant culture model, the level of p24 antigen in the supernatant
      from the inner foreskin was slightly higher than that from the outer foreskin,
      although this difference was not significant. The present study is the first to
      employ both CCR5 and alpha4beta7 to identify HIV target cells in the foreskin.
      Our data demonstrated that the inner foreskin was more enriched with HIV target
      immune cells than the outer foreskin, and this tissue was structured for
      efficient communication among immune cells that may promote HIV transmission and
      replication. In addition, our data suggests the R5-tropism of HIV sexual
      transmission is likely shaped through the inherent receptor composition on HIV
      target cells in the mucosa. 

PMID- 24454813
TI  - A self-adapting system for the automated detection of inter-ictal epileptiform
      discharges.
AB  - PURPOSE: Scalp EEG remains the standard clinical procedure for the diagnosis of
      epilepsy. Manual detection of inter-ictal epileptiform discharges (IEDs) is slow
      and cumbersome, and few automated methods are used to assist in practice. This is
      mostly due to low sensitivities, high false positive rates, or a lack of trust in
      the automated method. In this study we aim to find a solution that will make
      computer assisted detection more efficient than conventional methods, while
      preserving the detection certainty of a manual search. METHODS: Our solution
      consists of two phases. First, a detection phase finds all events similar to
      epileptiform activity by using a large database of template waveforms. Individual
      template detections are combined to form "IED nominations", each with a
      corresponding certainty value based on the reliability of their contributing
      templates. The second phase uses the ten nominations with highest certainty and
      presents them to the reviewer one by one for confirmation. Confirmations are used
      to update certainty values of the remaining nominations, and another iteration is
      performed where ten nominations with the highest certainty are presented. This
      continues until the reviewer is satisfied with what has been seen. Reviewer
      feedback is also used to update template accuracies globally and improve future
      detections. KEY FINDINGS: Using the described method and fifteen evaluation EEGs
      (241 IEDs), one third of all inter-ictal events were shown after one iteration,
      half after two iterations, and 74%, 90%, and 95% after 5, 10 and 15 iterations
      respectively. Reviewing fifteen iterations for the 20-30 min recordings 1 took
      approximately 5 min. SIGNIFICANCE: The proposed method shows a practical approach
      for combining automated detection with visual searching for inter-ictal
      epileptiform activity. Further evaluation is needed to verify its clinical
      feasibility and measure the added value it presents.

PMID- 24454814
TI  - Regional homogeneity of intrinsic brain activity in happy and unhappy
      individuals.
AB  - BACKGROUND: Why are some people happier than others? This question has intrigued
      many researchers. However, limited work has addressed this question within a
      neuroscientific framework. METHODS: The present study investigated the neural
      correlates of trait happiness using the resting-state functional magnetic
      resonance imaging (rs-fMRI) approach. Specifically, regional homogeneity (ReHo)
      was examined on two groups of young adults: happy and unhappy individuals (N = 25
      per group). RESULTS: Decreased ReHo in unhappy relative to happy individuals was
      observed within prefrontal cortex, medial temporal lobe, superior temporal lobe,
      and retrosplenial cortex. In contrast, increased ReHo in unhappy relative to
      happy individuals was observed within the dorsolateral prefrontal cortex, middle
      cingulate gyrus, putamen, and thalamus. In addition, the ReHo within the left
      thalamus was negatively correlated with Chinese Happiness Inventory (CHI) score
      within the happy group. LIMITATIONS: As an exploratory study, we examined how
      general trait happiness is reflected in the regional homogeneity of intrinsic
      brain activity in a relatively small sample. Examining other types of happiness
      in a larger sample using a multitude of intrinsic brain activity indices are
      warranted for future work. CONCLUSIONS: The local synchronization of BOLD signal
      is altered in unhappy individuals. The regions implicated in this alteration
      partly overlapped with previously identified default mode network, emotional
      circuitry, and rewarding system, suggesting that these systems may be involved in
      happiness.

PMID- 24454815
TI  - A snapshot of a coral "holobiont": a transcriptome assembly of the scleractinian
      coral, porites, captures a wide variety of genes from both the host and symbiotic
      zooxanthellae.
AB  - Massive scleractinian corals of the genus Porites are important reef builders in
      the Indo-Pacific, and they are more resistant to thermal stress than other stony
      corals, such as the genus Acropora. Because coral health and survival largely
      depend on the interaction between a coral host and its symbionts, it is important
      to understand the molecular interactions of an entire "coral holobiont". We
      simultaneously sequenced transcriptomes of Porites australiensis and its
      symbionts using the Illumina Hiseq2000 platform. We obtained 14.3 Gbp of
      sequencing data and assembled it into 74,997 contigs (average: 1,263 bp, N50
      size: 2,037 bp). We successfully distinguished contigs originating from the host
      (Porites) and the symbiont (Symbiodinium) by aligning nucleotide sequences with
      the decoded Acropora digitifera and Symbiodinium minutum genomes. In contrast to
      previous coral transcriptome studies, at least 35% of the sequences were found to
      have originated from the symbionts, indicating that it is possible to analyze
      both host and symbiont transcriptomes simultaneously. Conserved protein domain
      and KEGG analyses showed that the dataset contains broad gene repertoires of both
      Porites and Symbiodinium. Effective utilization of sequence reads revealed that
      the polymorphism rate in P. australiensis is 1.0% and identified the major
      symbiotic Symbiodinium as Type C15. Analyses of amino acid biosynthetic pathways
      suggested that this Porites holobiont is probably able to synthesize most of the
      common amino acids and that Symbiodinium is potentially able to provide essential
      amino acids to its host. We believe this to be the first molecular evidence of
      complementarity in amino acid metabolism between coral hosts and their symbionts.
      We successfully assembled genes originating from both the host coral and the
      symbiotic Symbiodinium to create a snapshot of the coral holobiont transcriptome.
      This dataset will facilitate a deeper understanding of molecular mechanisms of
      coral symbioses and stress responses. 

PMID- 24454816
TI  - A simple lattice model that captures protein folding, aggregation and amyloid
      formation.
AB  - The ability of many proteins to convert from their functional soluble state to
      amyloid fibrils can be attributed to inter-molecular beta strand formation. Such
      amyloid formation is associated with neurodegenerative disorders like Alzheimer's
      and Parkinson's. Molecular modelling can play a key role in providing insight
      into the factors that make proteins prone to fibril formation. However, fully
      atomistic models are computationally too expensive to capture the length and time
      scales associated with fibril formation. As the ability to form fibrils is the
      rule rather than the exception, much insight can be gained from the study of
      coarse-grained models that capture the key generic features associated with
      amyloid formation. Here we present a simple lattice model that can capture both
      protein folding and beta strand formation. Unlike standard lattice models, this
      model explicitly incorporates the formation of hydrogen bonds and the
      directionality of side chains. The simplicity of our model makes it
      computationally feasible to investigate the interplay between folding, amorphous
      aggregation and fibril formation, and maintains the capability of classic lattice
      models to simulate protein folding with high specificity. In our model, the
      folded proteins contain structures that resemble naturally occurring beta-sheets,
      with alternating polar and hydrophobic amino acids. Moreover, fibrils with
      intermolecular cross-beta strand conformations can be formed spontaneously out of
      multiple short hydrophobic peptide sequences. Both the formation of hydrogen
      bonds in folded structures and in fibrils is strongly dependent on the amino acid
      sequence, indicating that hydrogen-bonding interactions alone are not strong
      enough to initiate the formation of beta sheets. This result agrees with
      experimental observations that beta sheet and amyloid formation is strongly
      sequence dependent, with hydrophobic sequences being more prone to form such
      structures. Our model should open the way to a systematic study of the interplay
      between the factors that lead to amyloid formation. 

PMID- 24454817
TI  - Metabolic network analysis-based identification of antimicrobial drug targets in
      category A bioterrorism agents.
AB  - The 2001 anthrax mail attacks in the United States demonstrated the potential
      threat of bioterrorism, hence driving the need to develop sophisticated treatment
      and diagnostic protocols to counter biological warfare. Here, by performing flux
      balance analyses on the fully-annotated metabolic networks of multiple, whole
      genome-sequenced bacterial strains, we have identified a large number of
      metabolic enzymes as potential drug targets for each of the three Category A
      designated bioterrorism agents including Bacillus anthracis, Francisella
      tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme
      A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all
      strains across the three distinct genera were identified as targets.
      Antimicrobial agents against some of these enzymes are available. Thus, a
      combination of cross species-specific antibiotics and common antimicrobials
      against shared targets may represent a useful combinatorial therapeutic approach
      against all Category A bioterrorism agents. 

PMID- 24454818
TI  - Durable remission of renal cell carcinoma in conjuncture with graft versus host
      disease following allogeneic stem cell transplantation and donor lymphocyte
      infusion: rule or exception?
AB  - Allogeneic stem cell transplantation (alloSCT) followed by donor lymphocyte
      infusion (DLI) can be applied as immunotherapeutic intervention to treat
      malignant diseases. Here, we describe a patient with progressive metastatic clear
      cell renal cell carcinoma (RCC) who was treated with T cell depleted non
      myeloablative alloSCT and DLI resulting in disease regression accompanied by
      extensive graft versus host disease (GVHD). We characterized the specificity of
      this immune response, and detected a dominant T cell population recognizing a
      novel minor histocompatibility antigen (MiHA) designated LB-FUCA2-1V. T cells
      specific for LB-FUCA2-1V were shown to recognize RCC cell lines, supporting a
      dominant role in the graft versus tumor (GVT) reaction. However, coinciding with
      the gradual disappearance of chronic GVHD, the anti-tumor effect declined and 3
      years after alloSCT the metastases became progressive again. To re-initiate the
      GVT reaction, escalating doses of DLI were given, but no immune response could be
      induced and the patient died of progressive disease 8.5 years after alloSCT. Gene
      expression studies illustrated that only a minimal number of genes shared
      expression between RCC and professional antigen presenting cells but were not
      expressed by non-malignant healthy tissues, indicating that in patients suffering
      from RCC, GVT reactivity after alloSCT may be unavoidably linked to GVHD. 

PMID- 24454819
TI  - E2A predicts prognosis of colorectal cancer patients and regulates cancer cell
      growth by targeting miR-320a.
AB  - BACKGROUND AND OBJECTIVE: Transcriptional factor E2A is crucial for the normal
      development and differentiation of B and T lymphocytes. Dysregulation of E2A
      leads to leukemia and tumorigenesis of some solid tumors. The expression and
      clinical significance of E2A as well as its role in colorectal cancer (CRC) are
      still unknown. This study aims to assess E2A expression in CRC tissues, evaluate
      its prognosis value, and investigate its role in colon cancer cell growth.
      METHODS: E2A expression in CRC tissues and normal mucosa was detected by
      immunohistochemical staining; Kaplan-Meier survival curve and Cox regression
      model were used to evaluate the prognostic value of E2A. Lentivirus was used to
      construct E2A stably knocked-down cells. MTT assay was employed to detect cell
      proliferation change; cell cycle was analyzed by flow cytometry; and chromatin
      immunoprecipitation (ChIP) assay was used to validate the predicted binding
      target of E2A. RESULTS: Expression of E2A was lower in CRC tissues than normal
      mucosa; low E2A expression correlated with advanced TNM stage and larger tumor
      size, and predicted poor prognosis of CRC patients. E2A knockdown resulted in
      increased cell proliferation rate and cell cycle acceleration. ChIP assay showed
      miR-320a was a direct target of E2A and upregulation of miR-320a in E2A
      downregulated cells could reverse cell proliferation and cell cycle changes
      caused by E2A deficiency. CONCLUSIONS: E2A is an independent prognostic factor
      for CRC patients and targets miR-320a to regulate cell proliferation of colon
      cancer cells.

PMID- 24454820
TI  - Aerodynamic characteristics of a feathered dinosaur measured using physical
      models. Effects of form on static stability and control effectiveness.
AB  - We report the effects of posture and morphology on the static aerodynamic
      stability and control effectiveness of physical models based on the feathered
      dinosaur, [Formula: see text]Microraptor gui, from the Cretaceous of China.
      Postures had similar lift and drag coefficients and were broadly similar when
      simplified metrics of gliding were considered, but they exhibited different
      stability characteristics depending on the position of the legs and the presence
      of feathers on the legs and the tail. Both stability and the function of
      appendages in generating maneuvering forces and torques changed as the glide
      angle or angle of attack were changed. These are significant because they
      represent an aerial environment that may have shifted during the evolution of
      directed aerial descent and other aerial behaviors. Certain movements were
      particularly effective (symmetric movements of the wings and tail in pitch,
      asymmetric wing movements, some tail movements). Other appendages altered their
      function from creating yaws at high angle of attack to rolls at low angle of
      attack, or reversed their function entirely. While [Formula: see text]M. gui
      lived after [Formula: see text]Archaeopteryx and likely represents a side
      experiment with feathered morphology, the general patterns of stability and
      control effectiveness suggested from the manipulations of forelimb, hindlimb and
      tail morphology here may help understand the evolution of flight control
      aerodynamics in vertebrates. Though these results rest on a single specimen, as
      further fossils with different morphologies are tested, the findings here could
      be applied in a phylogenetic context to reveal biomechanical constraints on
      extinct flyers arising from the need to maneuver. 

PMID- 24454821
TI  - Transmembrane and coiled-coil domain family 1 is a novel protein of the
      endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is a continuous membrane network in eukaryotic
      cells comprising the nuclear envelope, the rough ER, and the smooth ER. The ER
      has multiple critical functions and a characteristic structure. In this study, we
      identified a new protein of the ER, TMCC1 (transmembrane and coiled-coil domain
      family 1). The TMCC family consists of at least 3 putative proteins (TMCC1-3)
      that are conserved from nematode to human. We show that TMCC1 is an ER protein
      that is expressed in diverse human cell lines. TMCC1 contains 2 adjacent
      transmembrane domains near the C-terminus, in addition to coiled-coil domains.
      TMCC1 was targeted to the rough ER through the transmembrane domains, whereas the
      N-terminal region and C-terminal tail of TMCC1 were found to reside in the
      cytoplasm. Moreover, the cytosolic region of TMCC1 formed homo- or hetero-dimers
      or oligomers with other TMCC proteins and interacted with ribosomal proteins.
      Notably, overexpression of TMCC1 or its transmembrane domains caused defects in
      ER morphology. Our results suggest roles of TMCC1 in ER organization. 

PMID- 24454822
TI  - The use of anchored agonists of phagocytic receptors for cancer immunotherapy:
      B16-F10 murine melanoma model.
AB  - The application of the phagocytic receptor agonists in cancer immunotherapy was
      studied. Agonists (laminarin, molecules with terminal mannose, N-Formyl
      methioninyl-leucyl-phenylalanine) were firmly anchored to the tumor cell surface.
      When particular agonists of phagocytic receptors were used together with LPS
      (Toll-like receptor agonist), high synergy causing tumour shrinkage and a
      temporary or permanent disappearance was observed. Methods of anchoring
      phagocytic receptor agonists (charge interactions, anchoring based on hydrophobic
      chains, covalent bonds) and various regimes of phagocytic agonist/LPS mixture
      applications were tested to achieve maximum therapeutic effect. Combinations of
      mannan/LPS and f-MLF/LPS (hydrophobic anchors) in appropriate (pulse) regimes
      resulted in an 80% and 60% recovery for mice, respectively. We propose that
      substantial synergy between agonists of phagocytic and Toll-like receptors (TLR)
      is based on two events. The TLR ligand induces early and massive inflammatory
      infiltration of tumors. The effect of this cell infiltrate is directed towards
      tumor cells, bearing agonists of phagocytic receptors on their surface. The
      result of these processes was effective killing of tumor cells. This novel
      approach represents exploitation of innate immunity mechanisms for treating
      cancer. 

PMID- 24454824
TI  - When none of us perform better than all of us together: the role of analogical
      decision rules in groups.
AB  - During social interactions, groups develop collective competencies that (ideally)
      should assist groups to outperform average standalone individual members (weak
      cognitive synergy) or the best performing member in the group (strong cognitive
      synergy). In two experimental studies we manipulate the type of decision rule
      used in group decision-making (identify the best vs. collaborative), and the way
      in which the decision rules are induced (direct vs. analogical) and we test the
      effect of these two manipulations on the emergence of strong and weak cognitive
      synergy. Our most important results indicate that an analogically induced
      decision rule (imitate-the-successful heuristic) in which groups have to identify
      the best member and build on his/her performance (take-the-best heuristic) is the
      most conducive for strong cognitive synergy. Our studies bring evidence for the
      role of analogy-making in groups as well as the role of fast-and-frugal
      heuristics for group decision-making. 

PMID- 24454823
TI  - Age related differences in dynamics of specific memory B cell populations after
      clinical pertussis infection.
AB  - For a better understanding of the maintenance of immune mechanisms to Bordetella
      pertussis (Bp) in relation to age, we investigated the dynamic range of specific
      B cell responses in various age-groups at different time points after a
      laboratory confirmed pertussis infection. Blood samples were obtained in a Dutch
      cross sectional observational study from symptomatic pertussis cases. Lymphocyte
      subpopulations were phenotyped by flowcytometry before and after culture. Memory
      B (Bmem) cells were differentiated into IgG antibody secreting cells (ASC) by
      polyclonal stimulation and detected by an ELISPOT assay specific for pertussis
      antigens pertussis toxin (Ptx), filamentous haemagglutinin (FHA) and pertactin
      (Prn). Bp antigen specific IgG concentrations in plasma were determined using
      multiplex technology. The majority of subjects having experienced a clinical
      pertussis episode demonstrated high levels of both Bp specific IgG and Bmem cell
      levels within the first 6 weeks after diagnosis. Significantly lower levels were
      observed thereafter. Waning of cellular and humoral immunity to maintenance
      levels occurred within 9 months after antigen encounter. Age was found to
      determine the maximum but not base-line frequencies of Bmem cell populations;
      higher levels of Bmem cells specific for Ptx and FHA were reached in adults and
      (pre-) elderly compared to under-fours and schoolchildren in the first 6 weeks
      after Bp exposure, whereas not in later phases. This age effect was less obvious
      for specific IgG levels. Nonetheless, subjects' levels of specific Bmem cells and
      specific IgG were weakly correlated. This is the first study to show that both
      age and closeness to last Bp encounter impacts the size of Bp specific Bmem cell
      and plasma IgG levels. 

PMID- 24454825
TI  - Role of receptor activity modifying protein 1 in function of the calcium sensing
      receptor in the human TT thyroid carcinoma cell line.
AB  - The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by
      sensing minute changes in serum Ca(2+) and modulating secretion of calciotropic
      hormones. It has been shown in transfected cells that accessory proteins known as
      Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are
      required for cell-surface trafficking of the CaSR. These effects have only been
      demonstrated in transfected cells, so their physiological relevance is unclear.
      Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid
      human carcinoma cells, RAMP1 is required for trafficking of the CaSR.
      Furthermore, we show that normal RAMP1 function is required for intracellular
      responses to ligands. Specifically, to confirm earlier studies with tagged
      constructs, and to provide the additional benefit of quantitative stoichiometric
      analysis, we used fluorescence resonance energy transfer to show equal abilities
      of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted
      more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than
      RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different
      ratios of RAMPs to CaSR. In order to determine relevance of these findings in an
      endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in
      medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3
      constitutively) and measured a significant 50% attenuation of signalling in
      response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using
      specific antibodies induced a concentration-dependent reduction in CaSR-mediated
      signalling in response to Cinacalcet in TT cells, suggesting a novel functional
      role for RAMP1 in regulation of CaSR signalling in addition to its known role in
      receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as
      higher-level oligomers and play a role in CaSR signalling even after cell surface
      localisation has occurred. 

PMID- 24454827
TI  - A semi-automated single day image differencing technique to identify animals in
      aerial imagery.
AB  - Our research presents a proof-of-concept that explores a new and innovative
      method to identify large animals in aerial imagery with single day image
      differencing. We acquired two aerial images of eight fenced pastures and
      conducted a principal component analysis of each image. We then subtracted the
      first principal component of the two pasture images followed by heuristic
      thresholding to generate polygons. The number of polygons represented the number
      of potential cattle (Bos taurus) and horses (Equus caballus) in the pasture. The
      process was considered semi-automated because we were not able to automate the
      identification of spatial or spectral thresholding values. Imagery was acquired
      concurrently with ground counts of animal numbers. Across the eight pastures, 82%
      of the animals were correctly identified, mean percent commission was 53%, and
      mean percent omission was 18%. The high commission error was due to small mis
      alignments generated from image-to-image registration, misidentified shadows, and
      grouping behavior of animals. The high probability of correctly identifying
      animals suggests short time interval image differencing could provide a new
      technique to enumerate wild ungulates occupying grassland ecosystems, especially
      in isolated or difficult to access areas. To our knowledge, this was the first
      attempt to use standard change detection techniques to identify and enumerate
      large ungulates. 

PMID- 24454826
TI  - E3 ubiquitin ligase Pub1 is implicated in endocytosis of a GPI-anchored protein
      Ecm33 in fission yeast.
AB  - We previously identified three glycosylphosphatidylinositol (GPI)-anchored
      proteins including Ecm33, as multicopy suppressors of the phenotypes of a mutant
      allele of cis4(+) that encodes a zinc transporter in fission yeast. Here, we
      further identified two multicopy suppressor genes, ubi1 (+) and ubc4 (+),
      encoding ubiquitin-ribosomal fusion protein and ubiquitin conjugating enzyme E2,
      respectively. In addition, Ubi1 or Ubc4 overexpression failed to suppress the
      phenotypes of the double deletion of cis4 (+) and pub1 (+) gene, which encodes a
      HECT-type ubiquitin ligase E3. During exponential phase GFP-Ecm33 localized at
      the growing cell tips of the cell surface and the medial region in wild-type
      cells. Notably, during the post-exponential and stationary phase, GFP-Ecm33 in
      wild-type cells was internalized and mostly localized to the Golgi/endosomes, but
      it was still stably localized at the cell surface in Deltapub1 cells. The
      Deltapub1 cells showed osomoremedial phenotypes to various drugs indicating their
      defects in cell wall integrity. Altogether, our findings reveal a novel role for
      Pub1 in endocytosis of Ecm33 and regulation of cell wall integrity in fission
      yeast. 

PMID- 24454828
TI  - MoPex19, which is essential for maintenance of peroxisomal structure and woronin
      bodies, is required for metabolism and development in the rice blast fungus.
AB  - Peroxisomes are present ubiquitously and make important contributions to cellular
      metabolism in eukaryotes. They play crucial roles in pathogenicity of plant
      fungal pathogens. The peroxisomal matrix proteins and peroxisomal membrane
      proteins (PMPs) are synthesized in the cytosol and imported post-translationally.
      Although the peroxisomal import machineries are generally conserved, some species
      specific features were found in different types of organisms. In phytopathogenic
      fungi, the pathways of the matrix proteins have been elucidated, while the import
      machinery of PMPs remains obscure. Here, we report that MoPEX19, an ortholog of
      ScPEX19, was required for PMPs import and peroxisomal maintenance, and played
      crucial roles in metabolism and pathogenicity of the rice blast fungus
      Magnaporthe oryzae. MoPEX19 was expressed in a low level and Mopex19p was
      distributed in the cytoplasm and newly formed peroxisomes. MoPEX19 deletion led
      to mislocalization of peroxisomal membrane proteins (PMPs), as well peroxisomal
      matrix proteins. Peroxisomal structures were totally absent in Deltamopex19
      mutants and woronin bodies also vanished. Deltamopex19 exhibited metabolic
      deficiency typical in peroxisomal disorders and also abnormality in glyoxylate
      cycle which was undetected in the known mopex mutants. The Deltamopex19 mutants
      performed multiple disorders in fungal development and pathogenicity-related
      morphogenesis, and lost completely the pathogenicity on its hosts. These data
      demonstrate that MoPEX19 plays crucial roles in maintenance of peroxisomal and
      peroxisome-derived structures and makes more contributions to fungal development
      and pathogenicity than the known MoPEX genes in the rice blast fungus. 

PMID- 24454829
TI  - Altered dynamics in the circadian oscillation of clock genes in dermal
      fibroblasts of patients suffering from idiopathic hypersomnia.
AB  - From single cell organisms to the most complex life forms, the 24-hour circadian
      rhythm is important for numerous aspects of physiology and behavior such as daily
      periodic fluctuations in body temperature and sleep-wake cycles. Influenced by
      environmental cues - mainly by light input -, the central pacemaker in the
      thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock
      mechanisms which are present in peripheral tissues. In order to correlate
      modifications in the molecular mechanisms of circadian rhythm with the
      pathophysiology of idiopathic hypersomnia, this study aimed to investigate the
      dynamics of the expression of circadian clock genes in dermal fibroblasts of
      idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC).
      Ten clinically and polysomnographically proven IH patients were recruited from
      the department of sleep medicine of the University Hospital of Muenster. Clinical
      diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep
      Latency Test (MSLT). Fourteen clinical healthy volunteers served as control
      group. Dermal fibroblasts were obtained via punch biopsy and grown in cell
      culture. The expression of circadian clock genes was investigated by
      semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming
      periodical oscillation of expression of the core circadian clock genes BMAL1,
      PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and
      PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over
      two circadian periods whereas the overall expression of only the key
      transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests
      for the first time an aberrant dynamics in the circadian clock in IH. These
      findings may serve to better understand some clinical features of the
      pathophysiology in sleep - wake rhythms in IH. 

PMID- 24454830
TI  - Ultrasonic elastography features of phyllodes tumors of the breast: a clinical
      research.
AB  - The purpose of this study was to analyze the ultrasonic elastography features of
      phyllodes tumors of the breast comparing with fibroadenomas. A retrospective
      database was queried for the patients diagnosed as phyllodes tumors and
      fibroadenomas at Sun Yat-sen Memorial Hospital from January 2008 to August 2012.
      Three hundred and fifty lesions from 323 consecutive patients were included in
      the study. All the cases were examined by conventional ultrasonography and
      ultrasound elastography. Ultrasound elastography was used to calculate strain
      ratio of the lesions with bilateral breast tissue at the same depth as reference.
      There were 36 phyllodes tumors (27 benign, 8 borderline, 1 malignant) and 314
      fibroadenomas (158 the pericanalicular type, 103 the intracanalicular type, 53
      other special types). The strain ratio for phyllodes tumors (3.19 +/- 2.33) was
      significantly higher than for fibroadenomas (1.69 +/- 0.88) (p<0.05). The
      Spearman(.)s correlation coefficient between strain ratio of ultrasound
      elastography and pathological groups was significant, with a value of 0.17
      (p<0.05). Ultrasound elastography could provide additional information to
      differentiate phyllodes tumors from fibroadenoma in breast.

PMID- 24454831
TI  - Effect of a multi-dimensional intervention programme on the motivation of
      physical education students.
AB  - This research study purports to verify the effect produced on the motivation of
      physical education students of a multi-dimensional programme in dance teaching
      sessions. This programme incorporates the application of teaching skills directed
      towards supporting the needs of autonomy, competence and relatedness. A quasi
      experimental design was carried out with two natural groups of 4(th) year
      Secondary Education students--control and experimental -, delivering 12 dance
      teaching sessions. A prior training programme was carried out with the teacher in
      the experimental group to support these needs. An initial and final measurement
      was taken in both groups and the results revealed that the students from the
      experimental group showed an increase of the perception of autonomy and, in
      general, of the level of self-determination towards the curricular content of
      corporal expression focused on dance in physical education. To this end, we
      highlight the programme's usefulness in increasing the students' motivation
      towards this content, which is so complicated for teachers of this area to
      develop.

PMID- 24454832
TI  - End criteria for reaching maximal oxygen uptake must be strict and adjusted to
      sex and age: a cross-sectional study.
AB  - OBJECTIVE: To describe different end criteria for reaching maximal oxygen uptake
      (VO2max) during a continuous graded exercise test on the treadmill, and to
      explore the manner by which different end criteria have an impact on the
      magnitude of the VO2max result. METHODS: A sample of 861 individuals (390 women)
      aged 20-85 years performed an exercise test on a treadmill until exhaustion. Gas
      exchange, heart rate, blood lactate concentration and Borg Scale6-20 rating were
      measured, and the impact of different end criteria on VO2max was studied;VO2
      leveling off, maximal heart rate (HRmax), different levels of respiratory
      exchange ratio (RER), and postexercise blood lactate concentration. RESULTS:
      Eight hundred and four healthy participants (93%) fulfilled the exercise test
      until voluntary exhaustion. There were no sex-related differences in HRmax, RER,
      or Borg Scale rating, whereas blood lactate concentration was 18% lower in women
      (P<0.001). Forty-two percent of the participants achieved a plateau in VO2; these
      individuals had 5% higher ventilation (P = 0.033), 4% higher RER (P<0.001), and
      5% higher blood lactate concentration (P = 0.047) compared with participants who
      did not reach a VO2 plateau. When using RER >=1.15 or blood lactate concentration
      >=8.0 mmol*L(-1), VO2max was 4% (P = 0.012) and 10% greater (P<0.001),
      respectively. A blood lactate concentration >=8.0 mmol*L(-1) excluded 63% of the
      participants in the 50-85-year-old cohort. CONCLUSIONS: A range of typical end
      criteria are presented in a random sample of subjects aged 20-85 years. The
      choice of end criteria will have an impact on the number of the participants as
      well as the VO2max outcome. Suggestions for new recommendations are given.

PMID- 24454833
TI  - Driving factors for the evolution of species-specific echolocation call design in
      new world free-tailed bats (molossidae).
AB  - Phylogeny, ecology, and sensorial constraints are thought to be the most
      important factors influencing echolocation call design in bats. The Molossidae is
      a diverse bat family with a majority of species restricted to tropical and
      subtropical regions. Most molossids are specialized to forage for insects in open
      space, and thus share similar navigational challenges. We use an unprecedented
      dataset on the echolocation calls of 8 genera and 18 species of New World
      molossids to explore how habitat, phylogenetic relatedness, body mass, and prey
      perception contribute to echolocation call design. Our results confirm that, with
      the exception of the genus Molossops, echolocation calls of these bats show a
      typical design for open space foraging. Two lines of evidence point to
      echolocation call structure of molossids reflecting phylogenetic relatedness.
      First, such structure is significantly more similar within than among genera.
      Second, except for allometric scaling, such structure is nearly the same in
      congeneric species. Despite contrasting body masses, 12 of 18 species call within
      a relatively narrow frequency range of 20 to 35 kHz, a finding that we explain by
      using a modeling approach whose results suggest this frequency range to be an
      adaptation optimizing prey perception in open space. To conclude, we argue that
      the high variability in echolocation call design of molossids is an advanced
      evolutionary trait allowing the flexible adjustment of echolocation systems to
      various sensorial challenges, while conserving sender identity for social
      communication. Unraveling evolutionary drivers for echolocation call design in
      bats has so far been hampered by the lack of adequate model organisms sharing a
      phylogenetic origin and facing similar sensorial challenges. We thus believe that
      knowledge of the echolocation call diversity of New World molossid bats may prove
      to be landmark to understand the evolution and functionality of species-specific
      signal design in bats. 

PMID- 24454834
TI  - Synergistic and antagonistic effects of salinity and pH on germination in
      switchgrass (Panicum virgatum L.).
AB  - The effects of salt-alkaline mixed stress on switchgrass were investigated by
      evaluating seed germination and the proline, malondialdehyde (MDA) and soluble
      sugar contents in three switchgrass (Panicum virgatum L.) cultivars in order to
      identify which can be successfully produced on marginal lands affected by salt
      alkaline mixed stress. The experimental conditions consisted of four levels of
      salinity (10, 60, 110 and 160 mM) and four pH levels (7.1, 8.3, 9.5 and 10.7).
      The effects of salt-alkaline mixed stress with equivalent coupling of the
      salinity and pH level on the switchgrass were explored via model analyses.
      Switchgrass was capable of germinating and surviving well in all treatments under
      low-alkaline pH (pH<=8.3), regardless of the salinity. However, seed germination
      and seedling growth were sharply reduced at higher pH values in conjunction with
      salinity. The salinity and pH had synergetic effects on the germination
      percentage, germination index, plumular length and the soluble sugar and proline
      contents in switchgrass. However, these two factors exhibited antagonistic
      effects on the radicular length of switchgrass. The combined effects of salinity
      and pH and the interactions between them should be considered when evaluating the
      strength of salt-alkaline mixed stress. 

PMID- 24454835
TI  - How do people attribute income-related inequalities in health? A cross-sectional
      study in Ontario, Canada.
AB  - CONTEXT: Substantive equity-focused policy changes in Ontario, Canada have yet to
      be realized and may be limited by a lack of widespread public support. An
      understanding of how the public attributes inequalities can be informative for
      developing widespread support. Therefore, the objectives of this study were to
      examine how Ontarians attribute income-related health inequalities. METHODS: We
      conducted a telephone survey of 2,006 Ontarians using random digit dialing. The
      survey included thirteen questions relevant to the theme of attributions of
      income-related health inequalities, with each statement linked to a known social
      determinant of health. The statements were further categorized depending on
      whether the statement was framed around blaming the poor for health inequalities,
      the plight of the poor as a cause of health inequalities, or the privilege of the
      rich as a cause of health inequalities. RESULTS: There was high agreement for
      statements that attributed inequalities to differences between the rich and the
      poor in terms of employment, social status, income and food security, and
      conversely, the least agreement for statements that attributed inequalities to
      differences in terms of early childhood development, social exclusion, the social
      gradient and personal health practices and coping skills. Mean agreement was
      lower for the two statements that suggested blame for income-related health
      inequalities lies with the poor (43.1%) than for the three statements that
      attributed inequalities to the plight of the poor (58.3%) or the eight statements
      that attributed inequalities to the privilege of the rich (58.7%). DISCUSSION: A
      majority of this sample of Ontarians were willing to attribute inequalities to
      the social determinants of health, and were willing to accept messages that
      framed inequalities around the privilege of the rich or the plight of the poor.
      These findings will inform education campaigns, campaigns aimed at increasing
      public support for equity-focused public policy, and knowledge translation
      strategies.

PMID- 24454836
TI  - PprA contributes to Deinococcus radiodurans resistance to nalidixic acid, genome
      maintenance after DNA damage and interacts with deinococcal topoisomerases.
AB  - PprA is known to contribute to Deinococcus radiodurans' remarkable capacity to
      survive a variety of genotoxic assaults. The molecular bases for PprA's role(s)
      in the maintenance of the damaged D. radiodurans genome are incompletely
      understood, but PprA is thought to promote D. radiodurans's capacity for DSB
      repair. PprA is found in a multiprotein DNA processing complex along with an ATP
      type DNA ligase, and the D. radiodurans toposiomerase IB (DraTopoIB) as well as
      other proteins. Here, we show that PprA is a key contributor to D. radiodurans
      resistance to nalidixic acid (Nal), an inhibitor of topoisomerase II. Growth of
      wild type D. radiodurans and a pprA mutant were similar in the absence of
      exogenous genotoxic insults; however, the pprA mutant exhibited marked growth
      delay and a higher frequency of anucleate cells following treatment with DNA
      damaging agents. We show that PprA interacts with both DraTopoIB and the Gyrase A
      subunit (DraGyrA) in vivo and that purified PprA enhances DraTopoIB catalysed
      relaxation of supercoiled DNA. Thus, besides promoting DNA repair, our findings
      suggest that PprA also contributes to preserving the integrity of the D.
      radiodurans genome following DNA damage by interacting with DNA topoisomerases
      and by facilitating the actions of DraTopoIB. 

PMID- 24454837
TI  - Density, destinations or both? A comparison of measures of walkability in
      relation to transportation behaviors, obesity and diabetes in Toronto, Canada.
AB  - The design of suburban communities encourages car dependency and discourages
      walking, characteristics that have been implicated in the rise of obesity.
      Walkability measures have been developed to capture these features of urban built
      environments. Our objective was to examine the individual and combined
      associations of residential density and the presence of walkable destinations,
      two of the most commonly used and potentially modifiable components of
      walkability measures, with transportation, overweight, obesity, and diabetes. We
      examined associations between a previously published walkability measure and
      transportation behaviors and health outcomes in Toronto, Canada, a city of 2.6
      million people in 2011. Data sources included the Canada census, a transportation
      survey, a national health survey and a validated administrative diabetes
      database. We depicted interactions between residential density and the
      availability of walkable destinations graphically and examined them statistically
      using general linear modeling. Individuals living in more walkable areas were
      more than twice as likely to walk, bicycle or use public transit and were
      significantly less likely to drive or own a vehicle compared with those living in
      less walkable areas. Individuals in less walkable areas were up to one-third more
      likely to be obese or to have diabetes. Residential density and the availability
      of walkable destinations were each significantly associated with transportation
      and health outcomes. The combination of high levels of both measures was
      associated with the highest levels of walking or bicycling (p<0.0001) and public
      transit use (p<0.0026) and the lowest levels of automobile trips (p<0.0001), and
      diabetes prevalence (p<0.0001). We conclude that both residential density and the
      availability of walkable destinations are good measures of urban walkability and
      can be recommended for use by policy-makers, planners and public health
      officials. In our setting, the combination of both factors provided additional
      explanatory power. 

PMID- 24454838
TI  - In vitro and in vivo enhancement of adipogenesis by Italian ryegrass (Lolium
      multiflorum) in 3T3-L1 cells and mice.
AB  - Adipogenesis is very much important in improving the quality of meat in animals.
      The aim of the present study was to investigate the in vitro and in vivo
      adipogenesis regulation properties of Lolium multiflorum on 3T3-L1 pre-adipocytes
      and mice. Chemical composition of petroleum ether extract of L. multiflorum (PET
      LM) confirmed the presence of fatty acids, such as alpha-linolenic acid,
      docosahexaenoic acid, oleic acid, docosatetraenoic acid, and caprylic acid, as
      the major compounds. PET-LM treatment increased viability, lipid accumulation,
      lipolysis, cell cycle progression, and DNA synthesis in the cells. PET-LM
      treatment also augmented peroxysome proliferator activated receptor (PPAR)
      gamma2, CCAAT/enhancer binding protein-alpha, adiponectin, adipocyte binding
      protein, glucose transporter-4, fatty acid synthase, and sterol regulatory
      element binding protein-1 expression at mRNA and protein levels in differentiated
      adipocytes. In addition, mice administered with 200 mg/kg body weight PET-LM for
      8 weeks showed greater body weight than control mice. These findings suggest that
      PET-LM facilitates adipogenesis by stimulating PPARgamma-mediated signaling
      cascades in adipocytes which could be useful for quality meat development in
      animals. 

PMID- 24454839
TI  - The strain at bone-implant interface determines the effect of spinopelvic
      reconstruction following total sacrectomy: a strain gauge analysis in various
      spinopelvic constructs.
AB  - PURPOSE: There is still some controversy regarding the optimal biomechanical
      concept for spinopelvic stabilization following total sacrectomy for malignancy.
      Strains at specific anatomical sites at pelvis/sacrum and implants interfaces
      have been poorly investigated. Herein, we compared and analyzed the strains
      applied at key points at the bone-implant interface in four different spinopelvic
      constructs following total sacrectomy; consequently, we defined a balanced
      architecture for spinopelvic fusion in that situation. METHODS: Six human
      cadaveric specimens, from second lumbar vertebra to proximal femur, were used to
      compare the partial strains at specific sites in a total sacrectomy model. Test
      constructs included: (1) intact pelvis (control), (2) sacral-rod reconstruction
      (SRR), (3) bilateral fibular flap reconstruction (BFFR), (4) four-rods
      reconstruction (FRR), and (5) improved compound reconstruction (ICR). Strains
      were measured by bonded strain gauges onto the surface of three specific sites
      (pubic rami, arcuate lines, and posterior spinal rods) under a 500 N axial load.
      RESULTS: ICR caused lower strains at specific sites and, moreover, on stress
      distribution and symmetry, compared to the other three constructs. Strains at
      pubic rami and arcuate lines following BFFR were lower than those following SRR,
      but higher at the posterior spinal rod construct. The different modes of strain
      distribution reflected different patient's parameter-related conditions. FRR
      model showed the highest strains at all sites because of the lack of an anterior
      bracing frame. CONCLUSIONS: The findings of this investigation suggest that both
      anterior bracing frame and the four-rods load dispersion provide significant load
      sharing. Additionally, these two constructs decrease the peak strains at bone
      implant interface, thus determining the theoretical surgical technique to achieve
      optimal stress dispersion and balance for spinopelvic reconstruction in early
      postoperative period following total sacrectomy.

PMID- 24454840
TI  - Spatially-explicit estimation of geographical representation in large-scale
      species distribution datasets.
AB  - Much ecological research relies on existing multispecies distribution datasets.
      Such datasets, however, can vary considerably in quality, extent, resolution or
      taxonomic coverage. We provide a framework for a spatially-explicit evaluation of
      geographical representation within large-scale species distribution datasets,
      using the comparison of an occurrence atlas with a range atlas dataset as a
      working example. Specifically, we compared occurrence maps for 3773 taxa from the
      widely-used Atlas Florae Europaeae (AFE) with digitised range maps for 2049 taxa
      of the lesser-known Atlas of North European Vascular Plants. We calculated the
      level of agreement at a 50-km spatial resolution using average latitudinal and
      longitudinal species range, and area of occupancy. Agreement in species
      distribution was calculated and mapped using Jaccard similarity index and a
      reduced major axis (RMA) regression analysis of species richness between the
      entire atlases (5221 taxa in total) and between co-occurring species (601 taxa).
      We found no difference in distribution ranges or in the area of occupancy
      frequency distribution, indicating that atlases were sufficiently overlapping for
      a valid comparison. The similarity index map showed high levels of agreement for
      central, western, and northern Europe. The RMA regression confirmed that
      geographical representation of AFE was low in areas with a sparse data recording
      history (e.g., Russia, Belarus and the Ukraine). For co-occurring species in
      south-eastern Europe, however, the Atlas of North European Vascular Plants showed
      remarkably higher richness estimations. Geographical representation of atlas data
      can be much more heterogeneous than often assumed. Level of agreement between
      datasets can be used to evaluate geographical representation within datasets.
      Merging atlases into a single dataset is worthwhile in spite of methodological
      differences, and helps to fill gaps in our knowledge of species distribution
      ranges. Species distribution dataset mergers, such as the one exemplified here,
      can serve as a baseline towards comprehensive species distribution datasets. 

PMID- 24454841
TI  - Food insecurity is associated with increased risk of non-adherence to
      antiretroviral therapy among HIV-infected adults in the Democratic Republic of
      Congo: a cross-sectional study.
AB  - BACKGROUND: Food insecurity is increasingly reported as an important barrier of
      patient adherence to antiretroviral therapy (ART) in both resource-poor and rich
      settings. However, unlike in resource rich-settings, very few quantitative
      studies to date have investigated the association of food insecurity with patient
      adherence to ART in Sub-Saharan Africa. The current study examines the
      association between food insecurity and adherence to ART among HIV-infected
      adults in the Democratic Republic of Congo (DRC). METHODS AND FINDINGS: This is a
      cross-sectional quantitative study of patients receiving ART at three private and
      one public health facilities in Kinshasa, DRC. Participants were consecutively
      recruited into the study between April and November 2012. Adherence was measured
      using a combined method coupling pharmacy refill and self-reported adherence.
      Food insecurity was the primary predictor, and was assessed using the Household
      Food Insecurity Access Scale (HFIAS). Of the 898 participants recruited into the
      study, 512 (57%) were food insecure, and 188 (20.9%) were not adherent to ART.
      Food insecurity was significantly associated with non-adherence to ART (AOR,
      2.06; CI, 1.38-3.09). We also found that perceived harmfulness of ART and
      psychological distress were associated respectively with increased (AOR, 1.95;
      CI, 1.15-3.32) and decreased (AOR, 0.31; CI, 0.11-0.83) odds of non-adherence to
      ART. CONCLUSION: Food insecurity is prevalent and a significant risk factor for
      non-adherence to ART among HIV-infected individuals in the DRC. Our findings
      highlight the urgent need for strategies to improve food access among HIV
      infected on ART in order to ensure patient adherence to ART and ultimately the
      long-term success of HIV treatment in Sub-Saharan Africa.

PMID- 24454842
TI  - Changes in oxidative damage, inflammation and [NAD(H)] with age in cerebrospinal
      fluid.
AB  - An extensive body of evidence indicates that oxidative stress and inflammation
      play a central role in the degenerative changes of systemic tissues in aging.
      However a comparatively limited amount of data is available to verify whether
      these processes also contribute to normal aging within the brain. High levels of
      oxidative damage results in key cellular changes including a reduction in
      available nicotinamide adenine dinucleotide (NAD(+)), an essential molecule
      required for a number of vital cellular processes including DNA repair, immune
      signaling and epigenetic processing. In this study we quantified changes in
      [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8
      OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy
      humans across a wide age range (24-91 years). CSF was collected from consenting
      patients who required a spinal tap for the administration of anesthetic. CSF of
      participants aged >45 years was found to contain increased levels of lipid
      peroxidation (F2-isoprostanes) (p = 0.04) and inflammation (IL-6) (p = 0.00) and
      decreased levels of both total antioxidant capacity (p = 0.00) and NAD(H) (p =
      0.05), compared to their younger counterparts. A positive association was also
      observed between plasma [NAD(H)] and CSF NAD(H) levels (p = 0.03). Further
      analysis of the data identified a relationship between alcohol intake and CSF
      [NAD(H)] and markers of inflammation. The CSF of participants who consumed >1
      standard drink of alcohol per day contained lower levels of NAD(H) compared to
      those who consumed no alcohol (p<0.05). An increase in CSF IL-6 was observed in
      participants who reported drinking >0-1 (p<0.05) and >1 (p<0.05) standard
      alcoholic drinks per day compared to those who did not drink alcohol. Taken
      together these data suggest a progressive age associated increase in oxidative
      damage, inflammation and reduced [NAD(H)] in the brain which may be exacerbated
      by alcohol intake. 

PMID- 24454843
TI  - Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal
      pigment epithelium (RPE) for the treatment of age-related macular degeneration.
AB  - Basic studies of human pluripotential stem cells have advanced rapidly and stem
      cell products are now seeing therapeutic applications. However, questions remain
      regarding the tumorigenic potential of such cells. Here, we report the
      tumorigenic potential of induced pluripotent stem cell (iPSC)-derived retinal
      pigment epithelium (RPE) for the treatment of wet-type, age-related macular
      degeneration (AMD). First, immunodeficient mouse strains (nude, SCID, NOD-SCID
      and NOG) were tested for HeLa cells' tumor-forming capacity by transplanting
      various cell doses subcutaneously with or without Matrigel. The 50% Tumor
      Producing Dose (TPD50 value) is the minimal dose of transplanted cells that
      generated tumors in 50% of animals. For HeLa cells, the TPD50 was the lowest when
      cells were embedded in Matrigel and transplanted into NOG mice (TPD50 = 10(1.1),
      n = 75). The TPD50 for undifferentiated iPSCs transplanted subcutaneously to NOG
      mice in Matrigel was 10(2.12); (n = 30). Based on these experiments, 1*10(6) iPSC
      derived RPE were transplanted subcutaneously with Matrigel, and no tumor was
      found during 15 months of monitoring (n = 65). Next, to model clinical
      application, we assessed the tumor-forming potential of HeLa cells and iPSC 201B7
      cells following subretinal transplantation of nude rats. The TPD50 for iPSCs was
      10(4.73) (n = 20) and for HeLa cells 10(1.32) (n = 37) respectively. Next, the
      tumorigenicity of iPSC-derived RPE was tested in the subretinal space of nude
      rats by transplanting 0.8-1.5*10(4) iPSC-derived RPE in a collagen-lined (1 mm*1
      mm) sheet. No tumor was found with iPSC-derived RPE sheets during 6-12 months of
      monitoring (n = 26). Considering the number of rodents used, the monitoring
      period, the sensitivity of detecting tumors via subcutaneous and subretinal
      administration routes and the incidence of tumor formation from the iPSC-derived
      RPE, we conclude that the tumorigenic potential of the iPSC-derived RPE was
      negligible. 

PMID- 24454844
TI  - Discovery of bile salt hydrolase inhibitors using an efficient high-throughput
      screening system.
AB  - The global trend of restricting the use of antibiotic growth promoters (AGP) in
      animal production necessitates the need to develop valid alternatives to maintain
      productivity and sustainability of food animals. Previous studies suggest
      inhibition of bile salt hydrolase (BSH), an intestinal bacteria-produced enzyme
      that exerts negative impact on host fat digestion and utilization, is a promising
      approach to promote animal growth performance. To achieve the long term goal of
      developing novel alternatives to AGPs, in this study, a rapid and convenient high
      throughput screening (HTS) system was developed and successfully used for
      identification of BSH inhibitors. With the aid of a high-purity BSH from a
      chicken Lactobacillus salivarius strain, we optimized various screening
      conditions (e.g. BSH concentration, reaction buffer pH, incubation temperature
      and length, substrate type and concentration) and establish a precipitation-based
      screening approach to identify BSH inhibitors using 96-well or 384-well
      microplates. A pilot HTS was performed using a small compound library comprised
      of 2,240 biologically active and structurally diverse compounds. Among the 107
      hits, several promising and potent BSH inhibitors (e.g. riboflavin and phenethyl
      caffeate) were selected and validated by standard BSH activity assay.
      Interestingly, the HTS also identified a panel of antibiotics as BSH inhibitor;
      in particular, various tetracycline antibiotics and roxarsone, the widely used
      AGP, have been demonstrated to display potent inhibitory effect on BSH. Together,
      this study developed an efficient HTS system and identified several BSH
      inhibitors with potential as alternatives to AGP. In addition, the findings from
      this study also suggest a new mode of action of AGP for promoting animal growth. 

PMID- 24454845
TI  - Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic
      glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.
AB  - The striatum plays an important role in linking cortical activity to basal
      ganglia outputs. Group I metabotropic glutamate receptors (mGluRs) are densely
      expressed in the medium spiny projection neurons and may be a therapeutic target
      for Parkinson's disease. The group I mGluRs are known to modulate the
      intracellular Ca(2+) signaling. To characterize Ca(2+) signaling in striatal
      cells, spontaneous cytoplasmic Ca(2+) transients were examined in acute slice
      preparations from transgenic mice expressing green fluorescent protein (GFP) in
      the astrocytes. In both the GFP-negative cells (putative-neurons) and astrocytes
      of the striatum, spontaneous slow and long-lasting intracellular Ca(2+)
      transients (referred to as slow Ca(2+) oscillations), which lasted up to
      approximately 200 s, were found. Neither the inhibition of action potentials nor
      ionotropic glutamate receptors blocked the slow Ca(2+) oscillation. Depletion of
      the intracellular Ca(2+) store and the blockade of inositol 1,4,5-trisphosphate
      receptors greatly reduced the transient rate of the slow Ca(2+) oscillation, and
      the application of an antagonist against mGluR5 also blocked the slow Ca(2+)
      oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol
      1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+)
      oscillation in both putative-neurons and astrocytes. The slow Ca(2+) oscillation
      features multicellular synchrony, and both putative-neurons and astrocytes
      participate in the synchronous activity. Therefore, the mGluR5-dependent slow
      Ca(2+) oscillation may involve in the neuron-glia interaction in the striatum. 

PMID- 24454846
TI  - Expression and replication studies to identify new candidate genes involved in
      normal hearing function.
AB  - Considerable progress has been made in identifying deafness genes, but still
      little is known about the genetic basis of normal variation in hearing function.
      We recently carried out a Genome Wide Association Study (GWAS) of quantitative
      hearing traits in southern European populations and found several SNPs with
      suggestive but none with significant association. In the current study, we
      followed up these SNPs to investigate which of them might show a genuine
      association with auditory function using alternative approaches. Firstly, we
      generated a shortlist of 19 genes from the published GWAS results. Secondly, we
      carried out immunocytochemistry to examine expression of these 19 genes in the
      mouse inner ear. Twelve of them showed distinctive cochlear expression patterns.
      Four showed expression restricted to sensory hair cells (Csmd1, Arsg, Slc16a6 and
      Gabrg3), one only in marginal cells of the stria vascularis (Dclk1) while the
      others (Ptprd, Grm8, GlyBP, Evi5, Rimbp2, Ank2, Cdh13) in multiple cochlear cell
      types. In the third step, we tested these 12 genes for replication of association
      in an independent set of samples from the Caucasus and Central Asia. Nine out of
      them showed nominally significant association (p<0.05). In particular, 4 were
      replicated at the same SNP and with the same effect direction while the remaining
      5 showed a significant association in a gene-based test. Finally, to look for
      genotype-phenotype relationship, the audiometric profiles of the three genotypes
      of the most strongly associated gene variants were analyzed. Seven out of the 9
      replicated genes (CDH13, GRM8, ANK2, SLC16A6, ARSG, RIMBP2 and DCLK1) showed an
      audiometric pattern with differences between different genotypes further
      supporting their role in hearing function. These data demonstrate the usefulness
      of this multistep approach in providing new insights into the molecular basis of
      hearing and may suggest new targets for treatment and prevention of hearing
      impairment. 

PMID- 24454847
TI  - Protein interactions and regulation of EscA in enterohemorrhagic E. coli.
AB  - Infections caused by enterohemorrhagic Escherichia coli (EHEC) can lead to
      diarrhea with abdominal cramps and sometimes are complicated by severe hemolytic
      uremic syndrome. EHEC secretes effector proteins into host cells through a type
      III secretion system that is composed of proteins encoded by a chromosomal
      island, locus for the enterocyte effacement (LEE). EspA is the major component of
      the filamentous structure connecting the bacteria and the host's cells. Synthesis
      and secretion of EspA must be carefully controlled since the protein is prone to
      polymerize. CesAB, CesA2, and EscL have been identified as being able to interact
      with EspA. Furthermore, the intracellular level of EspA declines when cesAB,
      cesA2, and escL are individually deleted. Here, we report a LEE gene named l0033,
      which also affects the intracellular level of EspA. We renamed l0033 as escA
      since its counterpart in enteropathogenic E. coli has been recently described.
      Similar to CesAB, EscL, and CesA2, EscA interacts with EspA and enhances the
      protein stability of EspA. However, EscA is also able to interact with inner
      membrane-associated EscL, CesA2, and EscN, but not with cytoplasmic CesAB. In
      terms of gene organizations, escA locates in LEE3. Expression of EscA is
      faithfully regulated via Mpc, the first gene product of LEE3. Since Mpc is
      tightly regulated to low level, we suggest that EscA is highly synchronized and
      critical to the process of escorting EspA to its final destination. 

PMID- 24454848
TI  - Human apolipoprotein e resequencing by proteomic analysis and its application to
      serotyping.
AB  - BACKGROUND: Apolipoprotein E (ApoE) typing is considered important because of the
      association between ApoE and Alzheimer's disease and familial dyslipidemia and is
      currently performed by genetic testing (APOE genotyping). ApoE levels in plasma
      and serum are clinically determined by immunoassay. METHODS: Combining an ApoE
      immunoassay reagent with proteomic analysis using an Orbitrap mass spectrometer,
      we attempted to resequence ApoE from trace amounts of serum for typing
      (serotyping). Most (24 of 33) ApoE mutant proteins registered to date with Online
      Mendelian Inheritance in Man, such as ApoE2 and ApoE4, involve lysine and
      arginine mutations. Digestion of mutant ApoE with trypsin will thus result in
      fragments that differ substantially from wild-type ApoE3 in terms of mass, making
      serotyping ideally suited to mass spectrometry analysis. RESULTS: The mean
      coverage of the amino acid sequence of full-length ApoE was 91.6% in the protein
      resequence. Residues 112 and 158 (which are mutated in ApoE2 and ApoE4) were
      covered in all samples, and the protein sequences were used for serotyping.
      Serotypes including all heterozygous combinations (ApoE2/E3, E2/E4, E3/E4)
      corresponded exactly to the APOE genotyping results in each of the subjects.
      CONCLUSION: Our novel ApoE serotyping method with protein resequencing requires
      no synthesis of stable isotope-labeled peptides or genome analysis. The method
      can use residual blood from samples collected for routine clinical tests, thus
      enabling retrospective studies with preserved body fluids. The test could be
      applied to samples from subjects whose DNA is unavailable. In future studies, we
      hope to demonstrate the capability of our method to detect rare ApoE mutations.

PMID- 24454850
TI  - Topical cream-based dosage forms of the macrocyclic drug delivery vehicle
      cucurbit[6]uril.
AB  - The macrocycle family of molecules called cucurbit[n]urils are potential drug
      delivery vehicles as they are able to form host-guest complexes with many
      different classes of drugs. This study aimed to examine the utility of
      Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised
      treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both
      buffered cream aqueous- and oily cream-based dosage forms. The solid state
      interaction of CB[6] with other excipients was studied by differential scanning
      calorimetry and the macrocycle's transdermal permeability was determined using
      rat skin. Significant solid state interactions were observed between CB[6] and
      the other dosage form excipients. At concentrations up to 32% w/w the buffered
      aqueous cream maintained its normal consistency and could be effectively applied
      to skin, but the oily cream was too stiff and is not suitable as a dosage form.
      Cucurbit[6]uril does not permeate through skin; as such, the results imply that
      cucurbituril-based topical creams may potentially only have applications for
      localised skin treatment and not for transdermal drug delivery. 

PMID- 24454849
TI  - Intragenic suppressor of Osiaa23 revealed a conserved tryptophan residue crucial
      for protein-protein interactions.
AB  - The Auxin/Indole-3-Acetic Acid (Aux/IAA) and Auxin Response Factor (ARF) are two
      important families that play key roles in auxin signal transduction. Both of the
      families contain a similar carboxyl-terminal domain (Domain III/IV) that
      facilitates interactions between these two families. In spite of the importance
      of protein-protein interactions among these transcription factors, the mechanisms
      involved in these interactions are largely unknown. In this study, we isolated
      six intragenic suppressors of an auxin insensitive mutant, Osiaa23. Among these
      suppressors, Osiaa23-R5 successfully rescued all the defects of the mutant.
      Sequence analysis revealed that an amino acid substitution occurred in the
      Tryptophan (W) residue in Domain IV of Osiaa23. Yeast two-hybrid experiments
      showed that the mutation in Domain IV prevents the protein-protein interactions
      between Osiaa23 and OsARFs. Phylogenetic analysis revealed that the W residue is
      conserved in both OsIAAs and OsARFs. Next, we performed site-specific amino acid
      substitutions within Domain IV of OsARFs, and the conserved W in Domain IV was
      exchanged by Serine (S). The mutated OsARF(WS)s can be released from the
      inhibition of Osiaa23 and maintain the transcriptional activities. Expression of
      OsARF(WS)s in Osiaa23 mutant rescued different defects of the mutant. Our results
      suggest a previously unknown importance of Domain IV in both families and provide
      an indirect way to investigate functions of OsARFs. 

PMID- 24454851
TI  - Low LDL-C and high HDL-C levels are associated with elevated serum transaminases
      amongst adults in the United States: a cross-sectional study.
AB  - BACKGROUND: Dyslipidemia, typically recognized as high serum triglyceride, high
      low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein
      cholesterol (HDL-C) levels, are associated with nonalcoholic fatty liver disease
      (NAFLD). However, low LDL-C levels could result from defects in lipoprotein
      metabolism or impaired liver synthetic function, and may serve as ab initio
      markers for unrecognized liver diseases. Whether such relationships exist in the
      general population has not been investigated. We hypothesized that despite common
      conception that low LDL-C is desirable, it might be associated with elevated
      liver enzymes due to metabolic liver diseases. METHODS AND FINDINGS: We examined
      the associations between alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and major components of serum lipid profiles in a
      nationally representative sample of 23,073 individuals, who had no chronic viral
      hepatitis and were not taking lipid-lowering medications, from the National
      Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. ALT and AST
      exhibited non-linear U-shaped associations with LDL-C and HDL-C, but not with
      triglyceride. After adjusting for potential confounders, individuals with LDL-C
      less than 40 and 41-70 mg/dL were associated with 4.2 (95% CI 1.5-11.7, p =
      0.007) and 1.6 (95% CI 1.1-2.5, p = 0.03) times higher odds of abnormal liver
      enzymes respectively, when compared with those with LDL-C values 71-100 mg/dL
      (reference group). Surprisingly, those with HDL-C levels above 100 mg/dL was
      associated with 3.2 (95% CI 2.1-5.0, p<0.001) times higher odds of abnormal liver
      enzymes, compared with HDL-C values of 61-80 mg/dL. CONCLUSIONS: Both low LDL-C
      and high HDL-C, often viewed as desirable, were associated with significantly
      higher odds of elevated transaminases in the general U.S. adult population. Our
      findings underscore an underestimated biological link between lipoprotein
      metabolism and liver diseases, and raise a potential need for liver evaluation
      among over 10 million people with particularly low LDL-C or high HDL-C in the
      United States.

PMID- 24454852
TI  - HIV-1 specific antibody titers and neutralization among chronically infected
      patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional
      study.
AB  - The majority of potent and broadly neutralizing antibodies against HIV-1 have
      been isolated from untreated patients with acute or chronic infection. To assess
      the extent of HIV-1 specific antibody response and neutralization after many
      years of virologic suppression from potent combination ART, we examined antibody
      binding titers and neutralization of 51 patients with chronic HIV-1 infection on
      suppressive ART for at least three years. In this cross-sectional analysis, we
      found high antibody titers against gp120, gp41, and the membrane proximal
      external region (MPER) in 59%, 43%, and 27% of patients, respectively. We
      observed significantly higher endpoint binding titers for gp120 and gp41 for
      patients with >10 compared to <= 10 years of detectable HIV RNA. Additionally, we
      observed higher median gp120 and gp41 antibody titers in patients with HIV RNA
      <50 copies/mL for <= 5 years. 22% of patients neutralized a HIV-1 primary isolate
      (HIV-1(JR-FL)) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly
      greater HIV-1(JR-FL) neutralization was found among patients with >10 years of
      detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for <= 10 years, p = 0.02)
      and a trend toward greater neutralization in patients with <= 5 years of HIV RNA
      <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All
      patients with neutralizing activity mediated successful phagocytosis of VLPs by
      THP-1 cells after antibody opsonization. Our findings of highly specific
      antibodies to several structural epitopes of HIV-1 with antibody effector
      functions and neutralizing activity after long-term suppressive ART, suggest
      continuous antigenic stimulation and evolution of HIV-specific antibody response
      occurs before and after suppression with ART. These patients, particularly those
      with slower HIV progression and more time with detectable viremia prior to
      initiation of suppressive ART, are a promising population to identify and further
      study functional antibodies against HIV-1.

PMID- 24454853
TI  - Inverse association between air pressure and rheumatoid arthritis synovitis.
AB  - Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients
      with RA recognize fluctuations of their joint synovitis according to changes of
      air pressure, but the correlations between them have never been addressed in
      large-scale association studies. To address this point we recruited large-scale
      assessments of RA activity in a Japanese population, and performed an association
      analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients
      were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management
      Alliance) database. Detailed correlations between air pressure and joint swelling
      or tenderness were analyzed separately for each of the 326 patients with more
      than 20 assessments to regulate intra-patient correlations. Association studies
      were also performed for seven consecutive days to identify the strongest
      correlations. Standardized multiple linear regression analysis was performed to
      evaluate independent influences from other meteorological factors. As a result,
      components of composite measures for RA disease activity revealed suggestive
      negative associations with air pressure. The 326 patients displayed significant
      negative mean correlations between air pressure and swellings or the sum of
      swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven
      consecutive days, the most significant mean negative correlations were observed
      for air pressure three days before evaluations of RA synovitis (p = 1.7 * 10(-7),
      0.00027, and 8.3 * 10(-8), for swellings, tenderness and the sum of them,
      respectively). Standardized multiple linear regression analysis revealed these
      associations were independent from humidity and temperature. Our findings suggest
      that air pressure is inversely associated with synovitis in patients with RA.

PMID- 24454854
TI  - Overexpression of RNF146 in non-small cell lung cancer enhances proliferation and
      invasion of tumors through the Wnt/beta-catenin signaling pathway.
AB  - Studies have suggested a possible correlation between the newly identified E3
      ubiquitin ligase ring finger protein 146 (RNF146) and tumor development. However,
      until now, studies on RNF146 have been restricted to poly(ADP-ribosyl)ation and
      ubiquitin ligation, whereas the role of RNF146 in tumor biology has rarely been
      reported. In the present study, the role of RNF146 in non-small cell lung cancer
      (NSCLC) was investigated. The results showed that the expression of RNF146 was
      increased in clinical lung cancer samples and cell lines. RNF146 expression
      correlated with tumor size, differentiation level, lymphatic metastasis, pTNM
      staging, and prognosis of patients in stage I. RNF146 expression was negatively
      correlated with Axin expression but positively correlated with the nuclear
      expression of beta-catenin in NSCLC tissues. RNF146 downregulated the expression
      of Axin in lung cancer cell lines and induced the expression and nuclear
      distribution of beta-catenin. Overexpression of RNF146 in NSCLC cell lines
      increased the levels of cyclinD1, cyclinE, and CDK4, promoted cell cycle G0/G1-S
      transitions, and regulated cell proliferation. Overexpression of RNF146 led to
      upregulated levels of matrix metalloproteinases 2 and 7 and enhanced lung cancer
      cell invasiveness, events that were mediated by the classical Wnt/beta-catenin
      signaling pathway. In summary, the data in the present study indicate that RNF146
      regulated the development and progression of NSCLC by enhancing cell growth,
      invasion, and survival, suggesting that RNF146 may be a potential treatment
      target in NSCLC. 

PMID- 24454855
TI  - Non-host volatile blend optimization for forest protection against the European
      spruce bark beetle, Ips typographus.
AB  - Conifer feeding bark beetles (Coleoptera, Curculionidae, Scolytinae) pose a
      serious economic threat to forest production. Volatiles released by non-host
      angiosperm plants (so called non-host volatiles, NHV) have been shown to reduce
      the risk of attack by many bark beetle species, including the European spruce
      bark beetle, Ips typographus. However, the most active blend for I. typographus,
      containing three green leaf volatiles (GLVs) in addition to the key compounds
      trans-conophthorin (tC) and verbenone, has been considered too expensive for use
      in large-scale management. To lower the cost and improve the applicability of
      NHV, we aim to simplify the blend without compromising its anti-attractant
      potency. Since the key compound tC is expensive in pure form, we also tested a
      crude version: technical grade trans-conophthorin (T-tC). In another attempt to
      find a more cost effective substitute for tC, we evaluated a more readily
      synthesized analog: dehydro-conophthorin (DHC). Our results showed that 1-hexanol
      alone could replace the three-component GLV blend containing 1-hexanol, (3Z)
      hexen-1-ol, and (2E)-hexen-1-ol. Furthermore, the release rate of tC could be
      reduced from 5 mg/day to 0.5 mg/day in a blend with 1-hexanol and (-)-verbenone
      without compromising the anti-attractant activity. We further show that T-tC was
      comparable with tC, whereas DHC was a less effective anti-attractant. DHC also
      elicited weaker physiological responses in the tC-responding olfactory receptor
      neuron class, providing a likely mechanistic explanation for its weaker anti
      attractive effect. Our results suggest a blend consisting of (-)-verbenone, 1
      hexanol and technical trans-conophthorin as a cost-efficient anti-attractant for
      forest protection against I. typographus. 

PMID- 24454856
TI  - Soil manganese enrichment from industrial inputs: a gastropod perspective.
AB  - Manganese is one of the most abundant metal in natural environments and serves as
      an essential microelement for all living systems. However, the enrichment of soil
      with manganese resulting from industrial inputs may threaten terrestrial
      ecosystems. Several studies have demonstrated harmful effects of manganese
      exposure by cutaneous contact and/or by soil ingestion to a wide range of soil
      invertebrates. The link between soil manganese and land snails has never been
      made although these invertebrates routinely come in contact with the upper soil
      horizons through cutaneous contact, egg-laying, and feeding activities in soil.
      Therefore, we have investigated the direct transfer of manganese from soils to
      snails and assessed its toxicity at background concentrations in the soil.
      Juvenile Cantareus aspersus snails were caged under semi-field conditions and
      exposed first, for a period of 30 days, to a series of soil manganese
      concentrations, and then, for a second period of 30 days, to soils with higher
      manganese concentrations. Manganese levels were measured in the snail
      hepatopancreas, foot, and shell. The snail survival and shell growth were used to
      assess the lethal and sublethal effects of manganese exposure. The transfer of
      manganese from soil to snails occurred independently of food ingestion, but had
      no consistent effect on either the snail survival or shell growth. The
      hepatopancreas was the best biomarker of manganese exposure, whereas the shell
      did not serve as a long-term sink for this metal. The kinetics of manganese
      retention in the hepatopancreas of snails previously exposed to manganese-spiked
      soils was significantly influenced by a new exposure event. The results of this
      study reveal the importance of land snails for manganese cycling in terrestrial
      biotopes and suggest that the direct transfer from soils to snails should be
      considered when precisely assessing the impact of anthropogenic Mn releases on
      soil ecosystems. 

PMID- 24454857
TI  - Deficient EBV-specific B- and T-cell response in patients with chronic fatigue
      syndrome.
AB  - Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger
      of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts
      with infectious mononucleosis and both enhanced and diminished EBV-specific
      antibody titers have been reported. In this study, we comprehensively analyzed
      the EBV-specific memory B- and T-cell response in patients with CFS. While we
      observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear
      antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients. Remarkably,
      when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or
      absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76%
      of patients. Moreover, the ex vivo EBV-induced secretion of TNF-alpha and IFN
      gamma was significantly lower in patients. Multicolor flow cytometry revealed
      that the frequencies of EBNA-1-specific triple TNF-alpha/IFN-gamma/IL-2 producing
      CD4(+) and CD8(+) T-cell subsets were significantly diminished whereas no
      difference could be detected for HCMV-specific T-cell responses. When comparing
      EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1
      RNA in CFS patients compared to healthy controls suggesting more frequent latent
      replication. Taken together, our findings give evidence for a deficient EBV
      specific B- and T-cell memory response in CFS patients and suggest an impaired
      ability to control early steps of EBV reactivation. In addition the diminished
      EBV response might be suitable to develop diagnostic marker in CFS. 

PMID- 24454858
TI  - EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human
      model?
AB  - Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2)
      are protein tyrosine kinases correlated with prognosis and response to therapy in
      a variety of human cancers. KRAS mediates the transduction of signals between
      EGFR and the nucleus, and its mutation has been identified as a predictor of
      resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER
      2/KRAS signalling pathway in gastric cancer is well established, and HER-2
      testing is required before initiating therapy. Conversely, this pathway has never
      been investigated in canine gastric tumours. A total of 19 canine gastric
      epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively
      evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational
      status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%)
      as diffuse-type. EGFR was overexpressed (>= 1+) in 8 (42.1%) cases and HER-2 (3+)
      in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The
      percentage of EGFR-positive tumours was significantly higher in the intestinal
      type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type
      in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon
      12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in
      canine gastric epithelial neoplasms. The potential presence of KRAS mutation
      should be taken into account as a possible mechanism of drug resistance. Further
      studies are necessary to evaluate the role of dog as a model for human gastric
      cancer.

PMID- 24454859
TI  - miR-24 regulates intrinsic apoptosis pathway in mouse cardiomyocytes.
AB  - Numerous cardiac diseases, including myocardial infarction (MI) and chronic heart
      failure, have been associated with cardiomyocyte apoptosis. Promoting cell
      survival by inhibiting apoptosis is one of the effective strategies to attenuate
      cardiac dysfunction caused by cardiomyocyte loss. miR-24 has been shown as an
      anti-apoptotic microRNA in various animal models. In vivo delivery of miR-24 into
      a mouse MI model suppressed cardiac cell death, attenuated infarct size, and
      rescued cardiac dysfunction. However, the molecular pathway by which miR-24
      inhibits cardiomyocyte apoptosis is not known. Here we found that miR-24
      negatively regulates mouse primary cadiomyocyte cell death through functioning in
      the intrinsic apoptotic pathways. In ER-mediated intrinsic pathway, miR-24
      genetically interacts with the CEBP homologous gene CHOP as knocking down of CHOP
      partially attenuated the induced apoptosis by miR-24 inhibition. In mitochondria
      involved intrinsic pathway, miR-24 inhibits the initiation of apoptosis through
      suppression of Cytochrome C release and Bax translocation from cytosol to
      mitochondria. These results provide mechanistic insights into the miR-24 mediated
      anti-apoptotic effects in murine cardiomyocytes. 

PMID- 24454860
TI  - Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone
      receptor function.
AB  - Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the
      functional orthologous nucleotide exchange factors of the heat shock protein 70
      kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while
      inducing different conformational changes of the ATPase domain of Hsp70. An
      appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein
      folding processes. Among Hsp70 client proteins are steroid receptors such as the
      glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the
      androgen receptor (AR). BAG-1 diversely affects steroid receptor activity, while
      to date the influence of HspBP1 on steroid receptor function is mostly unknown.
      Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid
      receptor folding complexes and steroid receptor activity. Coimmunoprecipitation
      studies indicated preferential binding of Hsp40 and the steroid receptors to BAG
      1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain
      of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as
      shown by pull-down assays. Reporter gene experiments revealed an inhibitory
      effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone
      concentrations at or approaching saturation. BAG-1M exhibited a transition from
      stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M
      levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic
      composition of steroid receptor folding complexes and on receptor function with
      important implications for steroid receptor physiology. 

PMID- 24454861
TI  - Distinct disease phases in muscles of facioscapulohumeral dystrophy patients
      identified by MR detected fat infiltration.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an untreatable disease,
      characterized by asymmetric progressive weakness of skeletal muscle with fatty
      infiltration. Although the main genetic defect has been uncovered, the downstream
      mechanisms causing FSHD are not understood. The objective of this study was to
      determine natural disease state and progression in muscles of FSHD patients and
      to establish diagnostic biomarkers by quantitative MRI of fat infiltration and
      phosphorylated metabolites. MRI was performed at 3T with dedicated coils on legs
      of 41 patients (28 men/13 women, age 34-76 years), of which eleven were re
      examined after four months of usual care. Muscular fat fraction was determined
      with multi spin-echo and T1 weighted MRI, edema by TIRM and phosphorylated
      metabolites by 3D (31)P MR spectroscopic imaging. Fat fractions were compared to
      clinical severity, muscle force, age, edema and phosphocreatine (PCr)/ATP.
      Longitudinal intramuscular fat fraction variation was analyzed by linear
      regression. Increased intramuscular fat correlated with age (p<0.05), FSHD
      severity score (p<0.0001), inversely with muscle strength (p<0.0001), and also
      occurred sub-clinically. Muscles were nearly dichotomously divided in those with
      high and with low fat fraction, with only 13% having an intermediate fat
      fraction. The intramuscular fat fraction along the muscle's length, increased
      from proximal to distal. This fat gradient was the steepest for intermediate fat
      infiltrated muscles (0.07+/-0.01/cm, p<0.001). Leg muscles in this intermediate
      phase showed a decreased PCr/ATP (p<0.05) and the fastest increase in fatty
      infiltration over time (0.18+/-0.15/year, p<0.001), which correlated with initial
      edema (p<0.01), if present. Thus, in the MR assessment of fat infiltration as
      biomarker for diseased muscles, the intramuscular fat distribution needs to be
      taken into account. Our results indicate that healthy individual leg muscles
      become diseased by entering a progressive phase with distal fat infiltration and
      altered energy metabolite levels. Fat replacement then relatively rapidly spreads
      over the whole muscle. 

PMID- 24454862
TI  - "A Body Shape Index" in middle-age and older Indonesian population: scaling
      exponents and association with incident hypertension.
AB  - BACKGROUND: "A Body Shape Index" (ABSI) is a recently proposed index that
      standardizes waist circumference for body mass index (BMI) and height. This study
      aims to: (a) examine if the ABSI scaling exponents for standardizing waist
      circumference for BMI and height are valid in middle-aged and older Indonesian
      population, and (b) compare the association between incident hypertension and
      ABSI and other anthropometric measures. METHODS AND FINDINGS: The Indonesian
      Family Life Survey Wave 3 measured anthropometric variables and blood pressure of
      8255 adults aged between 40 to 85 years in 2000. The relationship between two
      anthropometric quantities, e.g. weight (w) and height (h), can be expressed as
      the power law-equivalent [Formula: see text], where p = 2 is the scaling exponent
      in the derivation of the BMI and can be estimated by linear regression analysis.
      This was extended to the regression analysis of the log-transformed waist
      circumference, weight and height to establish the scaling exponents in the ABSI.
      The values for men were similar to those developed by the previous American
      study, which were 2/3 (BMI) and 1/2 (height). Those for women were somewhat
      smaller, at 3/5 (BMI) and 1/5 (height). The original (American) ABSI leads to
      mild negative correlation with BMI (-0.14) and height (-0.12) in the female
      population. Analysis of the development of hypertension between Waves 3 and 4
      (average interval 7.5 years) in relation to ABSI measured at Wave 3 showed
      stronger association if the locally derived (Indonesian) scaling exponents were
      used. However, both versions of the ABSI were less associated with incident
      hypertension than waist circumference and BMI. CONCLUSIONS: The values for the
      scaling exponents for ABSI are roughly similar between the American population
      and the middle-aged and older Indonesian population, although larger discrepancy
      was found in women. The ABSI is less associated with incident hypertension than
      waist circumference and BMI.

PMID- 24454863
TI  - Coxiella burnetii seroprevalence in small ruminants in The Gambia.
AB  - BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative
      bacterium present worldwide. Small ruminants are considered the main reservoirs
      for infection of humans. This study aimed to estimate the extent of C. burnetii
      infection among sheep and goats in part of The Gambia. METHODOLOGY/PRINCIPAL
      FINDINGS: This survey was carried out from March to May 2012 at two areas in The
      Gambia. The first area comprised a cluster of seven rural villages situated 5-15
      km west of Farafenni as well as the local abattoir. A second sampling was done at
      the central abattoir in Abuko (30 km from the capital, Banjul) in the Western
      Region. Serum samples were obtained from 490 goats and 398 sheep. In addition, 67
      milk samples were obtained from lactating dams. Sera were tested with a Q fever
      ELISA kit. C. burnetii DNA was extracted from milk samples and then detected
      using a specific quantitative multiplex PCR assay, targeting the IS1111a element.
      A multivariable mixed logistic regression model was used to examine the
      relationship between seropositivity and explanatory variables. An overall
      seroprevalence of 21.6% was found. Goats had a significantly higher
      seroprevalence than sheep, respectively 24.2% and 18.5%. Seropositive animals
      were significantly older than seronegative animals. Animals from the villages had
      a significantly lower seroprevalence than animals from the central abattoir
      (15.1% versus 29.1%). C. burnetii DNA was detected in 2 out of 67 milk samples,
      whereas 8 samples gave a doubtful result. CONCLUSION/SIGNIFICANCE: A substantial
      C. burnetii seroprevalence in sheep and goats in The Gambia was demonstrated.
      People living in close proximity to small ruminants are exposed to C. burnetii. Q
      fever should be considered as a possible cause of acute febrile illness in humans
      in The Gambia. Future studies should include a simultaneous assessment of
      veterinary and human serology, and include aetiology of febrile illness in local
      clinics.

PMID- 24454864
TI  - Bioinformatics analysis of bacterial annexins--putative ancestral relatives of
      eukaryotic annexins.
AB  - Annexins are Ca(2+)-binding, membrane-interacting proteins, widespread among
      eukaryotes, consisting usually of four structurally similar repeated domains. It
      is accepted that vertebrate annexins derive from a double genome duplication
      event. It has been postulated that a single domain annexin, if found, might
      represent a molecule related to the hypothetical ancestral annexin. The recent
      discovery of a single-domain annexin in a bacterium, Cytophaga hutchinsonii,
      apparently confirmed this hypothesis. Here, we present a more complex picture.
      Using remote sequence similarity detection tools, a survey of bacterial genomes
      was performed in search of annexin-like proteins. In total, we identified about
      thirty annexin homologues, including single-domain and multi-domain annexins, in
      seventeen bacterial species. The thorough search yielded, besides the known
      annexin homologue from C. hutchinsonii, homologues from the
      Bacteroidetes/Chlorobi phylum, from Gemmatimonadetes, from beta- and delta
      Proteobacteria, and from Actinobacteria. The sequences of bacterial annexins
      exhibited remote but statistically significant similarity to sequence profiles
      built of the eukaryotic ones. Some bacterial annexins are equipped with
      additional, different domains, for example those characteristic for toxins. The
      variation in bacterial annexin sequences, much wider than that observed in
      eukaryotes, and different domain architectures suggest that annexins found in
      bacteria may actually descend from an ancestral bacterial annexin, from which
      eukaryotic annexins also originate. The hypothesis of an ancient origin of
      bacterial annexins has to be reconciled with the fact that remarkably few
      bacterial strains possess annexin genes compared to the thousands of known
      bacterial genomes and with the patchy, anomalous phylogenetic distribution of
      bacterial annexins. Thus, a massive annexin gene loss in several bacterial
      lineages or very divergent evolution would appear a likely explanation.
      Alternative evolutionary scenarios, involving horizontal gene transfer between
      bacteria and protozoan eukaryotes, in either direction, appear much less likely.
      Altogether, current evidence does not allow unequivocal judgement as to the
      origin of bacterial annexins. 

PMID- 24454865
TI  - Effectiveness of anti-psychotics and related drugs in the Huntington French
      speaking group cohort.
AB  - PURPOSE: Huntington's disease is a rare condition. Patients are commonly treated
      with antipsychotics and tetrabenazine. The evidence of their effect on disease
      progression is limited and no comparative study between these drugs has been
      conducted. We therefore compared the effectiveness of antipsychotics on disease
      progression. METHODS: 956 patients from the Huntington French Speaking Group were
      followed for up to 8 years between 2002 and 2010. The effectiveness of treatments
      was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and
      then compared using a mixed model adjusted on a multiple propensity score.
      RESULTS: 63% of patients were treated with antipsychotics during the survey
      period. The most commonly prescribed medications were dibenzodiazepines (38%),
      risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no
      difference between treatments on the motor and behavioural declines observed,
      after taking the patient profiles at the start of the drug prescription into
      account. In contrast, the functional decline was lower in the dibenzodiazepine
      group than the other antipsychotic groups (Total Functional Capacity: 0.41 +/-
      0.17 units per year vs. risperidone and 0.54 +/- 0.19 vs. tetrabenazine, both
      p<0.05). Benzamides were less effective than other antipsychotics on cognitive
      evolution (Stroop interference, Stroop color and Literal fluency: p<0.05).
      CONCLUSIONS: Antipsychotics are widely used to treat patients with Huntington's
      disease. Although differences in motor or behavioural profiles between patients
      according to the antipsychotics used were small, there were differences in drug
      effectiveness on the evolution of functional and cognitive scores.

PMID- 24454866
TI  - Long-term sorption of metals is similar among plastic types: implications for
      plastic debris in aquatic environments.
AB  - Concerns regarding plastic debris and its ability to accumulate large
      concentrations of priority pollutants in the aquatic environment led us to
      quantify relationships between different types of mass-produced plastic and
      metals in seawater. At three locations in San Diego Bay, we measured the
      accumulation of nine targeted metals (aluminum, chromium, manganese, iron,
      cobalt, nickel, zinc, cadmium and lead) sampling at 1, 3, 6, 9 and 12 months, to
      five plastic types: polyethylene terephthalate (PET), high-density polyethylene
      (HDPE), polyvinyl chloride (PVC), low-density polyethylene (LDPE), and
      polypropylene (PP). Accumulation patterns were not consistent over space and
      time, and in general all types of plastic tended to accumulate similar
      concentrations of metals. When we did observe significant differences among
      concentrations of metals at a single sampling period or location in San Diego
      Bay, we found that HDPE typically accumulated lesser concentrations of metals
      than the other four polymers. Furthermore, over the 12-month study period,
      concentrations of all metals increased over time, and chromium, manganese,
      cobalt, nickel, zinc and lead did not reach saturation on at least one plastic
      type during the entire 12-month exposure. This suggests that plastic debris may
      accumulate greater concentrations of metals the longer it remains at sea.
      Overall, our work shows that a complex mixture of metals, including those listed
      as priority pollutants by the US EPA (Cd, Ni, Zn and Pb), can be found on plastic
      debris composed of various plastic types. 

PMID- 24454867
TI  - Quantitative phenotyping-based in vivo chemical screening in a zebrafish model of
      leukemia stem cell xenotransplantation.
AB  - Zebrafish-based chemical screening has recently emerged as a rapid and efficient
      method to identify important compounds that modulate specific biological
      processes and to test the therapeutic efficacy in disease models, including
      cancer. In leukemia, the ablation of leukemia stem cells (LSCs) is necessary to
      permanently eradicate the leukemia cell population. However, because of the very
      small number of LSCs in leukemia cell populations, their use in
      xenotransplantation studies (in vivo) and the difficulties in functionally and
      pathophysiologically replicating clinical conditions in cell culture experiments
      (in vitro), the progress of drug discovery for LSC inhibitors has been painfully
      slow. In this study, we developed a novel phenotype-based in vivo screening
      method using LSCs xenotransplanted into zebrafish. Aldehyde dehydrogenase
      positive (ALDH+) cells were purified from chronic myelogenous leukemia K562 cells
      tagged with a fluorescent protein (Kusabira-orange) and then implanted in young
      zebrafish at 48 hours post-fertilization. Twenty-four hours after
      transplantation, the animals were treated with one of eight different therapeutic
      agents (imatinib, dasatinib, parthenolide, TDZD-8, arsenic trioxide, niclosamide,
      salinomycin, and thioridazine). Cancer cell proliferation, and cell migration
      were determined by high-content imaging. Of the eight compounds that were tested,
      all except imatinib and dasatinib selectively inhibited ALDH+ cell proliferation
      in zebrafish. In addition, these anti-LSC agents suppressed tumor cell migration
      in LSC-xenotransplants. Our approach offers a simple, rapid, and reliable in vivo
      screening system that facilitates the phenotype-driven discovery of drugs
      effective in suppressing LSCs. 

PMID- 24454868
TI  - Connectivity features for identifying cognitive impairment in presymptomatic
      carotid stenosis.
AB  - Severe asymptomatic stenosis of the internal carotid artery (ICA) leads to
      increased incidence of mild cognitive impairment (MCI) likely through silent
      embolic infarcts and/or chronic hypoperfusion, but the brain dysfunction is
      poorly understood and difficult to diagnose. Thirty cognitively intact subjects
      with asymptomatic, severe (>= 70%), unilateral stenosis of the ICA were compared
      with 30 healthy controls, matched for age, sex, cardiovascular risk factors and
      education level, on a battery of neuropsychiatric tests, voxel-based morphometry
      of magnetic resonance imaging (MRI), diffusion tensor imaging and brain-wise,
      seed-based analysis of resting-state functional MRI. Multivariate regression
      models and multivariate pattern classification (support vector machines) were
      computed to assess the relationship between connectivity measures and
      neurocognitive performance. The patients had worse dizziness scores and poorer
      verbal memory, executive function and complex visuo-spatial performance than
      controls. Twelve out of the 30 patients (40%) were considered to have MCI.
      Nonetheless, the leukoaraiosis Sheltens scores, hippocampal and brain volumes
      were not different between groups. Their whole-brain mean fractional anisotropy
      (FA) was significantly reduced and regional functional connectivity (Fc) was
      significantly impaired in the dorsal attention network (DAN), frontoparietal
      network, sensorimotor network and default mode network. In particular, the Fc
      strength at the insula of the DAN and the mean FA were linearly related with
      attention performance and dizziness severity, respectively. The multivariate
      pattern classification gave over 90% predictive accuracy of individuals with MCI
      or severe dizziness. Cognitive decline in stroke-free individuals with severe
      carotid stenosis may arise from nonselective widespread disconnections of long
      range, predominantly interhemispheric non-hippocampal pathways. Connectivity
      measures may serve as both predictors for cases at risk and therapeutic targets
      for mitigating vascular cognitive impairment.

PMID- 24454869
TI  - Selective attention modulates human auditory brainstem responses: relative
      contributions of frequency and spatial cues.
AB  - Selective attention is the mechanism that allows focusing one's attention on a
      particular stimulus while filtering out a range of other stimuli, for instance,
      on a single conversation in a noisy room. Attending to one sound source rather
      than another changes activity in the human auditory cortex, but it is unclear
      whether attention to different acoustic features, such as voice pitch and speaker
      location, modulates subcortical activity. Studies using a dichotic listening
      paradigm indicated that auditory brainstem processing may be modulated by the
      direction of attention. We investigated whether endogenous selective attention to
      one of two speech signals affects amplitude and phase locking in auditory
      brainstem responses when the signals were either discriminable by frequency
      content alone, or by frequency content and spatial location. Frequency-following
      responses to the speech sounds were significantly modulated in both conditions.
      The modulation was specific to the task-relevant frequency band. The effect was
      stronger when both frequency and spatial information were available. Patterns of
      response were variable between participants, and were correlated with
      psychophysical discriminability of the stimuli, suggesting that the modulation
      was biologically relevant. Our results demonstrate that auditory brainstem
      responses are susceptible to efferent modulation related to behavioral goals.
      Furthermore they suggest that mechanisms of selective attention actively shape
      activity at early subcortical processing stages according to task relevance and
      based on frequency and spatial cues. 

PMID- 24454870
TI  - Prognostic significance and molecular mechanism of ATP-binding cassette subfamily
      C member 4 in resistance to neoadjuvant radiotherapy of locally advanced rectal
      carcinoma.
AB  - BACKGROUND: Mechanism of radioresistance in rectal carcinoma remains largely
      unknown. We aimed to evaluate the predictive role of ATP-binding cassette
      subfamily C member 4 (ABCC4) in locally advanced rectal carcinoma and explore
      possible molecular mechanisms by which ABCC4 confers the resistance to
      neoadjuvant radiotherapy. METHODS: The expression of ABCC4 and P53 mutant in
      biopsy tissue specimens from 121 locally advanced rectal carcinoma patients was
      examined using immunohistochemistry. The factors contributing to 3-year overall
      survival and disease-free survival were evaluated using the Kaplan-Meier method
      and Cox proportional hazard model. Lentivirus-mediated small hairpin RNA was
      applied to inhibit ABCC4 expression in colorectal carcinoma cell line RKO, and
      investigate the radiosensitivity in xenograft model. Intracellular cyclic
      adenosine monophosphate concentration and cell cycle distribution following
      irradiation were detected. RESULTS: High expression of ABCC4 and p53 mutant in
      pretreated tumors, poor pathological response, and high final tumor staging were
      significant factors independently predicted an unfavorable prognosis of locally
      advanced rectal carcinoma patients after neoadjuvant radiotherapy. Down
      regulation of ABCC4 expression significantly enhanced irradiation-induced
      suppression of tumor growth in xenograft model. Furthermore, down-regulation of
      ABCC4 expression enhanced intracellular cyclic adenosine monophosphate production
      and noticeable deficiency of G1-S phase checkpoint in cell cycle following
      irradiation. CONCLUSIONS: Our study suggests that ABCC4 serves as a novel
      predictive biomarker that is responsible for the radioresistance and predicts a
      poor prognosis for locally advanced rectal carcinoma after neoadjuvant
      radiotherapy.

PMID- 24454871
TI  - Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi
      correlates significantly with birth weight.
AB  - CONTEXT: Fetal growth involves highly complex molecular pathways. IGF2 is a key
      paternally expressed growth hormone that is critical for in utero growth in mice.
      Its role in human fetal growth has remained ambiguous, as it has only been
      studied in term tissues. Conversely the maternally expressed growth suppressor,
      PHLDA2, has a significant negative correlation between its term placental
      expression and birth weight. OBJECTIVE: The aim of this study is to address the
      role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and
      IGF2R, and PHLDA2 on term birth weight. DESIGN: Real-time quantitative PCR was
      used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in
      chorionic villus samples (CVS) (n = 260) collected at 11-13 weeks' gestation.
      Expression was correlated with term birth weight using statistical package R
      including correction for several confounding factors. RESULTS: Transcript levels
      of IGF2 and IGF2R revealed a significant positive correlation with birth weight
      (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2
      and birth weight. Critically, small for gestational age (SGA) neonates had
      significantly lower IGF2 levels than appropriate for gestational age neonates (p
      = 3.6 * 10(-7)). INTERPRETATION: Our findings show that IGF2 mRNA levels at 12
      weeks gestation could provide a useful predictor of future fetal growth to term,
      potentially predicting SGA babies. SGA babies are known to be at a higher risk
      for type 2 diabetes. This research reveals an imprinted, parentally driven
      rheostat for in utero growth.

PMID- 24454872
TI  - Immunogenic, but not steady-state, antigen presentation permits regulatory T
      cells to control CD8+ T-cell effector differentiation by IL-2 modulation.
AB  - Absorption of IL-2 is one proposed mechanism of CD4+CD25+FoxP3+ regulatory T cell
      (Treg) suppression. Direct in vivo experimental evidence for this has recently
      been obtained. While modulation of IL-2 bioavailability controls CD8+ T-cell
      effector differentiation under strongly immunogenic conditions it is not known
      whether Treg modulate CD8+ T cell responses through this mechanism under steady
      state conditions. Here we assess this using a mouse model in which dendritic
      cells (DC) are manipulated to present cognate antigen to CD8+ T cells either in
      the steady-state or after activation. Our observations show that Treg exert a
      check on expansion and effector differentiation of CD8+ T cells under strongly
      immunogenic conditions associated with TLR ligand activation of DC, and this is
      mediated by limiting IL-2 availability. In contrast, when DC remain unactivated,
      depletion of Treg has little apparent effect on effector differentiation or IL-2
      homeostasis. We conclude that while modulation of IL-2 homeostasis is an
      important mechanism through which Treg control CD8+ effector differentiation
      under immunogenic conditions, this mechanism plays little role in modulating CD8+
      T-cell differentiation under steady-state conditions. 

PMID- 24454873
TI  - Interleukin 17 receptor A modulates monocyte subsets and macrophage generation in
      vivo.
AB  - Interleukin (IL)-17A signaling via Interleukin 17 receptor A (Il17ra) contributes
      to the inflammatory host response by inducing recruitment of innate immune cells,
      but also plays a role in homeostatic neutrophilic granulocyte regulation.
      Monocytes, the other main innate immune cell, have a longer life span and can
      pursue multiple differentiation pathways towards tissue macrophages. Monocytes
      are divided into two subpopulations by expression of the Ly6C/Gr1 surface marker
      in mice. We here investigated the role of Il17ra in monocyte homeostasis and
      macrophage generation. In Il17ra(-/-) and in mixed bone marrow chimeric
      wt/Il17ra(-/-) mice, the concentrations of circulating Il17ra(-/-) Gr1(low)
      monocytes were significantly decreased compared to wt cells. Pulmonary, splenic
      and resident peritoneal Il17ra(-/-) macrophages were significantly fewer than of
      wt origin. Bone marrow progenitor and monocyte numbers were equal, but the
      proportion of Il17ra(-/-) Gr1(low) monocytes was already decreased at bone marrow
      level. After monocyte depletion, initial Gr1(high) and Gr1(low) monocyte
      regeneration of Il17ra(-/-) and wt cells was very similar. However, Il17ra(-/-)
      Gr1(low) counts were not sustained. After labeling with either fluorescent beads
      or BrdU, Il17ra(-/-) Gr1(high) monocyte transition to Gr1(low) cells was not
      detectable unlike wt cells. Monocyte recruitment in acute peritonitis, which is
      known to be largely due to Gr1(high) cell migration, was unaffected in an
      identical environment. Unilateral ureteral obstruction induces a less acute
      inflammatory and fibrotic kidney injury. Compared to wt cells in the same
      environment, Il17ra(-/-) macrophage accumulation in the kidney was decreased. In
      the absence of Il17ra on all myeloid cells, renal fibrosis was significantly
      attenuated. Our data show that Il17ra modulates Gr1(low) monocyte counts and
      suggest defective Gr1(high) to Gr1(low) monocyte transition as an underlying
      mechanism. Lack of Il17ra altered homeostatic tissue macrophage formation and
      diminished renal inflammation and fibrosis. Il17ra appears to be a novel
      modulator of monocyte phenotype and possible therapeutic target in renal
      fibrosis. 

PMID- 24454874
TI  - Development of a novel heart failure risk tool: the barcelona bio-heart failure
      risk calculator (BCN bio-HF calculator).
AB  - BACKGROUND: A combination of clinical and routine laboratory data with biomarkers
      reflecting different pathophysiological pathways may help to refine risk
      stratification in heart failure (HF). A novel calculator (BCN Bio-HF calculator)
      incorporating N-terminal pro B-type natriuretic peptide (NT-proBNP, a marker of
      myocardial stretch), high-sensitivity cardiac troponin T (hs-cTnT, a marker of
      myocyte injury), and high-sensitivity soluble ST2 (ST2), (reflective of
      myocardial fibrosis and remodeling) was developed. METHODS: Model performance was
      evaluated using discrimination, calibration, and reclassification tools for 1-, 2
      , and 3-year mortality. Ten-fold cross-validation with 1000 bootstrapping was
      used. RESULTS: The BCN Bio-HF calculator was derived from 864 consecutive
      outpatients (72% men) with mean age 68.2 +/- 12 years (73%/27% New York Heart
      Association (NYHA) class I-II/III-IV, LVEF 36%, ischemic etiology 52.2%) and
      followed for a median of 3.4 years (305 deaths). After an initial evaluation of
      23 variables, eight independent models were developed. The variables included in
      these models were age, sex, NYHA functional class, left ventricular ejection
      fraction, serum sodium, estimated glomerular filtration rate, hemoglobin, loop
      diuretic dose, beta-blocker, Angiotensin converting enzyme inhibitor/Angiotensin
      2 receptor blocker and statin treatments, and hs-cTnT, ST2, and NT-proBNP levels.
      The calculator may run with the availability of none, one, two, or the three
      biomarkers. The calculated risk of death was significantly changed by additive
      biomarker data. The average C-statistic in cross-validation analysis was 0.79.
      CONCLUSIONS: A new HF risk-calculator that incorporates available biomarkers
      reflecting different pathophysiological pathways better allowed individual
      prediction of death at 1, 2, and 3 years.

PMID- 24454875
TI  - The government of Kenya's cash transfer program reduces the risk of sexual debut
      among young people age 15-25.
AB  - The aim of this study is to assess whether the Government of Kenya's Cash
      Transfer for Orphans and Vulnerable Children (Kenya CT-OVC) can reduce the risk
      of HIV among young people by postponing sexual debut. The program provides an
      unconditional transfer of US$20 per month directly to the main caregiver in the
      household. An evaluation of the program was implemented in 2007-2009 in seven
      districts. Fourteen Locations were randomly assigned to receive the program and
      fourteen were assigned to a control arm. A sample of households was enrolled in
      the evaluation in 2007. We revisited these households in 2011 and collected
      information on sexual activity among individuals between 15-25 years of age. We
      used logistic regression, adjusted for the respondent's age, sex and relationship
      to caregiver, the age, sex and schooling of the caregiver and whether or not the
      household lived in Nairobi at baseline, to compare rates of sexual debut among
      young people living in program households with those living in control households
      who had not yet entered the program. Our results, adjusted for these covariates,
      show that the program reduced the odds of sexual debut by 31 percent. There were
      no statistically significant effects on secondary outcomes of behavioral risk
      such as condom use, number of partners and transactional sex. Since the CT-OVC
      provides cash to the caregiver and not to the child, and there are no explicit
      conditions associated with receipt, these impacts are indirect, and may have been
      achieved by keeping young people in school. Our results suggest that large-scale
      national social cash transfer programs with poverty alleviation objectives may
      have potential positive spillover benefits in terms of reducing HIV risk among
      young people in Eastern and Southern Africa. 

PMID- 24454876
TI  - RanBP9 overexpression accelerates loss of pre and postsynaptic proteins in the
      APDeltaE9 transgenic mouse brain.
AB  - There is now compelling evidence that the neurodegenerative process in
      Alzheimer's disease (AD) begins in synapses. Loss of synaptic proteins and
      functional synapses in the amyloid precursor protein (APP) transgenic mouse
      models of AD is well established. However, what is the earliest age at which such
      loss of synapses occurs, and whether known markers of AD progression accelerate
      functional deficits is completely unknown. We previously showed that RanBP9
      overexpression leads to robustly increased amyloid beta peptide (Abeta)
      generation leading to enhanced amyloid plaque burden in a mouse model of AD. In
      this study we compared synaptic protein levels among four genotypes of mice,
      i.e., RanBP9 single transgenic (Ran), APDeltaE9 double transgenic (Dbl),
      APDeltaE9/RanBP9 triple transgenic (Tpl) and wild-type (WT) controls. We found
      significant reductions in the levels of synaptic proteins in both cortex and
      hippocampus of 5- and 6-months-old but not 3- or 4-months-old mice. Specifically,
      at 5-months of age, rab3A was reduced in the triple transgenic mice only in the
      cortex by 25% (p<0.05) and gap43 levels were reduced only in the hippocampus by
      44% (p<0.01) compared to wild-type (WT) controls. Interestingly, RanBP9
      overexpression in the Tpl mice reduced gap43 levels by a further 31% (p<0.05)
      compared to APDeltaE9 mice. RanBP9 also further decreased the levels of drebrin
      in the hippocampus by 32% (p<0.01) and chromogranin in the cortex by 24% (p<0.05)
      compared to APDeltaE9 mice. At 6-months of age, RanBP9 expression in the cortex
      led to further reduction of rab3A by 30% (p<0.05) and drebrin by 38% (p<0.01)
      compared to APDeltaE9 mice. RanBP9 also increased Abeta oligomers in the cortex
      at 6 months. Similarly, in the hippocampus, RanBP9 expression further reduced
      rab3A levels by 36% (p<0.01) and drebrin levels by 33% (p<0.01). Taken together
      these data suggest that RanBP9 overexpression accelerates loss of synaptic
      proteins in the mouse brain. 

PMID- 24454877
TI  - DNA barcoding for the identification of sand fly species (Diptera, Psychodidae,
      Phlebotominae) in Colombia.
AB  - Sand flies include a group of insects that are of medical importance and that
      vary in geographic distribution, ecology, and pathogen transmission.
      Approximately 163 species of sand flies have been reported in Colombia.
      Surveillance of the presence of sand fly species and the actualization of species
      distribution are important for predicting risks for and monitoring the expansion
      of diseases which sand flies can transmit. Currently, the identification of
      phlebotomine sand flies is based on morphological characters. However,
      morphological identification requires considerable skills and taxonomic
      expertise. In addition, significant morphological similarity between some
      species, especially among females, may cause difficulties during the
      identification process. DNA-based approaches have become increasingly useful and
      promising tools for estimating sand fly diversity and for ensuring the rapid and
      accurate identification of species. A partial sequence of the mitochondrial
      cytochrome oxidase gene subunit I (COI) is currently being used to differentiate
      species in different animal taxa, including insects, and it is referred as a
      barcoding sequence. The present study explored the utility of the DNA barcode
      approach for the identification of phlebotomine sand flies in Colombia. We
      sequenced 700 bp of the COI gene from 36 species collected from different
      geographic localities. The COI barcode sequence divergence within a single
      species was <2% in most cases, whereas this divergence ranged from 9% to 26.6%
      among different species. These results indicated that the barcoding gene
      correctly discriminated among the previously morphologically identified species
      with an efficacy of nearly 100%. Analyses of the generated sequences indicated
      that the observed species groupings were consistent with the morphological
      identifications. In conclusion, the barcoding gene was useful for species
      discrimination in sand flies from Colombia. 

PMID- 24454878
TI  - Dysferlin and other non-red cell proteins accumulate in the red cell membrane of
      Diamond-Blackfan Anemia patients.
AB  - Diamond Blackfan Anemia (DBA) is a congenital anemia usually caused by diverse
      mutations in ribosomal proteins. Although the genetics of DBA are well
      characterized, the mechanisms that lead to macrocytic anemia remain unclear. We
      systematically analyzed the proteomes of red blood cell membranes from multiple
      DBA patients to determine whether abnormalities in protein translation or
      erythropoiesis contribute to the observed macrocytosis or alterations in the
      mature red blood cell membrane. In depth proteome analysis of red cell membranes
      enabled highly reproducible identification and quantitative comparisons of 1100
      or more proteins. These comparisons revealed clear differences between red cell
      membrane proteomes in DBA patients and healthy controls that were consistent
      across DBA patients with different ribosomal gene mutations. Proteins exhibiting
      changes in abundance included those known to be increased in DBA such as fetal
      hemoglobin and a number of proteins not normally found in mature red cell
      membranes, including proteins involved in the major histocompatibility complex
      class I pathway. Most striking was the presence of dysferlin in the red blood
      cell membranes of DBA patients but absent in healthy controls. Immunoblot
      validation using red cell membranes isolated from additional DBA patients and
      healthy controls confirmed a distinct membrane protein signature specific to
      patients with DBA. 

PMID- 24454880
TI  - Evidence of spondyloarthropathy in the spine of a phytosaur (Reptilia:
      Archosauriformes) from the Late Triassic of Halberstadt, Germany.
AB  - Pathologies in the skeleton of phytosaurs, extinct archosauriform reptiles
      restricted to the Late Triassic, have only been rarely described. The only known
      postcranial pathologies of a phytosaur are two pairs of fused vertebrae of
      "Angistorhinopsis ruetimeyeri" from Halberstadt, Germany, as initially described
      by the paleontologist Friedrich von Huene. These pathologic vertebrae are
      redescribed in more detail in this study in the light of modern paleopathologic
      methods. Four different pathologic observations can be made in the vertebral
      column of this individual: 1) fusion of two thoracic vertebral bodies by new bone
      formation within the synovial membrane and articular capsule of the
      intervertebral joint; 2) fusion and conspicuous antero-posterior shortening of
      last presacral and first sacral vertebral bodies; 3) destruction and erosion of
      the anterior articular surface of the last presacral vertebra; and 4) a smooth
      depression on the ventral surface of the fused last presacral and first sacral
      vertebral bodies. Observations 1-3 can most plausibly and parsimoniously be
      attributed to one disease: spondyloarthropathy, an aseptic inflammatory process
      in which affected vertebrae show typical types of reactive new bone formation and
      erosion of subchondral bone. The kind of vertebral shortening present in the
      fused lumbosacral vertebrae suggests that the phytosaur acquired this disease in
      its early life. Observation 4, the smooth ventral depression in the fused
      lumbosacral vertebrae, is most probably not connected to the spondyloarthropathy,
      and can be regarded as a separate abnormality. It remains of uncertain origin,
      but may be the result of pressure, perhaps caused by a benign mass such as an
      aneurysm or cyst of unknown type. Reports of spondyloarthropathy in Paleozoic and
      Mesozoic reptiles are still exceptional, and our report of spondyloarthropathy in
      fossil material from Halberstadt is the first unequivocal occurrence of this
      disease in a Triassic tetrapod and in a phytosaur. 

PMID- 24454879
TI  - Transciptome analysis of the gill and swimbladder of Takifugu rubripes by RNA
      Seq.
AB  - The fish gill, as one of the mucosal barriers, plays an important role in mucosal
      immune response. The fish swimbladder functions for regulating buoyancy. The fish
      swimbladder has long been postulated as a homologous organ of the tetrapod lung,
      but the molecular evidence is scarce. In order to provide new information that is
      complementary to gill immune genes, initiate new research directions concerning
      the genetic basis of the gill immune response and understand the molecular
      function of swimbladder as well as its relationship with lungs, transcriptome
      analysis of the fugu Takifugu rubripes gill and swimbladder was carried out by
      RNA-Seq. Approximately 55,061,524 and 44,736,850 raw sequence reads from gill and
      swimbladder were generated, respectively. Gene ontology (GO) and KEGG pathway
      analysis revealed diverse biological functions and processes. Transcriptome
      comparison between gill and swimbladder resulted in 3,790 differentially
      expressed genes, of which 1,520 were up-regulated in the swimbladder while 2,270
      were down-regulated. In addition, 406 up regulated isoforms and 296 down
      regulated isoforms were observed in swimbladder in comparison to gill. By the
      gene enrichment analysis, the three immune-related pathways and 32 immune-related
      genes in gill were identified. In swimbladder, five pathways including 43
      swimbladder-enriched genes were identified. This work should set the foundation
      for studying immune-related genes for the mucosal immunity and provide genomic
      resources to study the relatedness of the fish swimbladder and mammalian lung. 

PMID- 24454881
TI  - Hydrogen sulfide prolongs postharvest storage of fresh-cut pears (Pyrus
      pyrifolia) by alleviation of oxidative damage and inhibition of fungal growth.
AB  - Hydrogen sulfide (H2S) has proved to be a multifunctional signaling molecule in
      plants and animals. Here, we investigated the role of H2S in the decay of fresh
      cut pears (Pyrus pyrifolia). H2S gas released by sodium hydrosulfide (NaHS)
      prolonged the shelf life of fresh-cut pear slices in a dose-dependent manner.
      Moreover, H2S maintained higher levels of reducing sugar and soluble protein in
      pear slices. H2S significantly reduced the accumulation of hydrogen peroxide
      (H2O2), superoxide radicals (*O2(-)) and malondialdehyde (MDA). Further
      investigation showed that H2S fumigation up-regulated the activities of
      antioxidant enzymes ascorbate peroxidase (APX), catalase (CAT), and guaiacol
      peroxidase (POD), while it down-regulated those of lipoxygenase (LOX),
      phenylalanine ammonia lyase (PAL) and polyphenol oxidase (PPO). Furthermore, H2S
      fumigation effectively inhibited the growth of two fungal pathogens of pear,
      Aspergillus niger and Penicillium expansum, suggesting that H2S can be developed
      as an effective fungicide for postharvest storage. The present study implies that
      H2S is involved in prolonging postharvest storage of pears by acting as an
      antioxidant and fungicide.

PMID- 24454882
TI  - GABAA receptors containing rho1 subunits contribute to in vivo effects of ethanol
      in mice.
AB  - GABAA receptors consisting of rho1, rho2, or rho3 subunits in homo- or hetero
      pentamers have been studied mainly in retina but are detected in many brain
      regions. Receptors formed from rho1 are inhibited by low ethanol concentrations,
      and family-based association analyses have linked rho subunit genes with alcohol
      dependence. We determined if genetic deletion of rho1 in mice altered in vivo
      ethanol effects. Null mutant male mice showed reduced ethanol consumption and
      preference in a two-bottle choice test with no differences in preference for
      saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration
      of ethanol-induced loss of righting reflex (LORR), and males were more sensitive
      to ethanol-induced motor sedation. In contrast, rho1 null mice showed faster
      recovery from acute motor incoordination produced by ethanol. Null mutant females
      were less sensitive to ethanol-induced development of conditioned taste aversion.
      Measurement of mRNA levels in cerebellum showed that deletion of rho1 did not
      change expression of rho2, alpha2, or alpha6 GABAA receptor subunits. (S)-4-amino
      cyclopent-1-enyl butylphosphinic acid ("rho1" antagonist), when administered to
      wild type mice, mimicked the changes that ethanol induced in rho1 null mice (LORR
      and rotarod tests), but the rho1 antagonist did not produce these effects in rho1
      null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid ("rho2"
      antagonist) did not change ethanol actions in wild type but produced effects in
      mice lacking rho1 that were opposite of the effects of deleting (or inhibiting)
      rho1. These results suggest that rho1 has a predominant role in two in vivo
      effects of ethanol, and a role for rho2 may be revealed when rho1 is deleted. We
      also found that ethanol produces similar inhibition of function of recombinant
      rho1 and rho2 receptors. These data indicate that ethanol action on GABAA
      receptors containing rho1/rho2 subunits may be important for specific effects of
      ethanol in vivo. 

PMID- 24454884
TI  - Recidivism and rehabilitation of criminal offenders: a carrot and stick
      evolutionary game.
AB  - Motivated by recent efforts by the criminal justice system to treat and
      rehabilitate nonviolent offenders rather than focusing solely on their
      punishment, we introduce an evolutionary game theoretic model to study the
      effects of "carrot and stick" intervention programs on criminal recidivism. We
      use stochastic simulations to study the evolution of a population where
      individuals may commit crimes depending on their past history, surrounding
      environment and, in the case of recidivists, on any counseling, educational or
      training programs available to them after being punished for their previous
      crimes. These sociological factors are embodied by effective parameters that
      determine the decision making probabilities. Players may decide to permanently
      reform or continue engaging in criminal activity, eventually reaching a state
      where they are considered incorrigible. Depending on parameter choices, the
      outcome of the game is a society with a majority of virtuous, rehabilitated
      citizens or incorrigibles. Since total resources may be limited, we constrain the
      combined punishment and rehabilitation costs per crime to be fixed, so that
      increasing one effort will necessarily decrease the other. We find that the most
      successful strategy in reducing crime is to optimally allocate resources so that
      after being punished, criminals experience impactful intervention programs,
      especially during the first stages of their return to society. Excessively harsh
      or lenient punishments are less effective. We also develop a system of coupled
      ordinary differential equations with memory effects to give a qualitative
      description of our simulated societal dynamics. We discuss our findings and
      sociological implications. 

PMID- 24454883
TI  - The MoxR ATPase RavA and its cofactor ViaA interact with the NADH:ubiquinone
      oxidoreductase I in Escherichia coli.
AB  - MoxR ATPases are widespread throughout bacteria and archaea. The experimental
      evidence to date suggests that these proteins have chaperone-like roles in
      facilitating the maturation of dedicated protein complexes that are functionally
      diverse. In Escherichia coli, the MoxR ATPase RavA and its putative cofactor ViaA
      are found to exist in early stationary-phase cells at 37  degrees C at low levels
      of about 350 and 90 molecules per cell, respectively. Both proteins are
      predominantly localized to the cytoplasm, but ViaA was also unexpectedly found to
      localize to the cell membrane. Whole genome microarrays and synthetic lethality
      studies both indicated that RavA-ViaA are genetically linked to Fe-S cluster
      assembly and specific respiratory pathways. Systematic analysis of mutant strains
      of ravA and viaA indicated that RavA-ViaA sensitizes cells to sublethal
      concentrations of aminoglycosides. Furthermore, this effect was dependent on
      RavA's ATPase activity, and on the presence of specific subunits of
      NADH:ubiquinone oxidoreductase I (Nuo Complex, or Complex I). Importantly, both
      RavA and ViaA were found to physically interact with specific Nuo subunits. We
      propose that RavA-ViaA facilitate the maturation of the Nuo complex.

PMID- 24454885
TI  - Efficient gene silencing mediated by tobacco rattle virus in an emerging model
      plant physalis.
AB  - The fruit of Physalis has a berry and a novelty called inflated calyx syndrome
      (ICS, also named the 'Chinese lantern'). Elucidation of the underlying
      developmental mechanisms of fruit diversity demands an efficient gene functional
      inference platform. Here, we tested the application of the tobacco rattle virus
      (TRV)-mediated gene-silencing system in Physalis floridana. First, we
      characterized the putative gene of a phytoene desaturase in P. floridana (PfPDS).
      Infecting the leaves of the Physalis seedlings with the PfPDS-TRV vector resulted
      in a bleached plant, including the developing leaves, floral organs, ICS, berry,
      and seed. These results indicated that a local VIGS treatment can efficiently
      induce a systemic mutated phenotype. qRT-PCR analyses revealed that the bleaching
      extent correlated to the mRNA reduction of the endogenous PfPDS. Detailed
      comparisons of multiple infiltration and growth protocols allowed us to determine
      the optimal methodologies for VIGS manipulation in Physalis. We subsequently
      utilized this optimized VIGS methodology to downregulate the expression of two
      MADS-box genes, MPF2 and MPF3, and compared the resulting effects with gene
      downregulation mediated by RNA interference (RNAi) methods. The VIGS-mediated
      gene knockdown plants were found to resemble the mutated phenotypes of floral
      calyx, fruiting calyx and pollen maturation of the RNAi transgenic plants for
      both MPF2 and MPF3. Moreover, the two MADS-box genes were appeared to have a
      novel role in the pedicel development in P. floridana. The major advantage of
      VIGS-based gene knockdown lies in practical aspects of saving time and easy
      manipulation as compared to the RNAi. Despite the lack of heritability and mosaic
      mutation phenotypes observed in some organs, the TRV-mediated gene silencing
      system provides an alternative efficient way to infer gene function in various
      developmental processes in Physalis, thus facilitating understanding of the
      genetic basis of the evolution and development of the morphological diversities
      within the Solanaceae. 

PMID- 24454886
TI  - Mapping reef fish and the seascape: using acoustics and spatial modeling to guide
      coastal management.
AB  - Reef fish distributions are patchy in time and space with some coral reef
      habitats supporting higher densities (i.e., aggregations) of fish than others.
      Identifying and quantifying fish aggregations (particularly during spawning
      events) are often top priorities for coastal managers. However, the rapid mapping
      of these aggregations using conventional survey methods (e.g., non-technical
      SCUBA diving and remotely operated cameras) are limited by depth, visibility and
      time. Acoustic sensors (i.e., splitbeam and multibeam echosounders) are not
      constrained by these same limitations, and were used to concurrently map and
      quantify the location, density and size of reef fish along with seafloor
      structure in two, separate locations in the U.S. Virgin Islands. Reef fish
      aggregations were documented along the shelf edge, an ecologically important
      ecotone in the region. Fish were grouped into three classes according to body
      size, and relationships with the benthic seascape were modeled in one area using
      Boosted Regression Trees. These models were validated in a second area to test
      their predictive performance in locations where fish have not been mapped. Models
      predicting the density of large fish (>= 29 cm) performed well (i.e., AUC =
      0.77). Water depth and standard deviation of depth were the most influential
      predictors at two spatial scales (100 and 300 m). Models of small (<= 11 cm) and
      medium (12-28 cm) fish performed poorly (i.e., AUC = 0.49 to 0.68) due to the
      high prevalence (45-79%) of smaller fish in both locations, and the unequal
      prevalence of smaller fish in the training and validation areas. Integrating
      acoustic sensors with spatial modeling offers a new and reliable approach to
      rapidly identify fish aggregations and to predict the density large fish in un
      surveyed locations. This integrative approach will help coastal managers to
      prioritize sites, and focus their limited resources on areas that may be of
      higher conservation value.

PMID- 24454887
TI  - Mathematical modeling predicts enhanced growth of X-ray irradiated pigmented
      fungi.
AB  - Ionizing radiation is known for its cytotoxic and mutagenic properties. However,
      recent evidence suggests that chronic sub-lethal irradiation stimulates the
      growth of melanin-pigmented (melanized) fungi, supporting the hypothesis that
      interactions between melanin and ionizing photons generate energy useful for
      fungal growth, and/or regulate growth-promoting genes. There are no quantitative
      models of how fungal proliferation is affected by ionizing photon energy, dose
      rate, and presence versus absence of melanin on the same genetic background. Here
      we present such a model, which we test using experimental data on melanin
      modulated radiation-induced proliferation enhancement in the fungus Cryptococcus
      neoformans, exposed to two different peak energies (150 and 320 kVp) over a wide
      range of X-ray dose rates. Our analysis demonstrates that radiation-induced
      proliferation enhancement in C. neoformans behaves as a binary "on/off"
      phenomenon, which is triggered by dose rates <0.002 mGy/h, and stays in the "on"
      position. A competing dose rate-dependent growth inhibition becomes apparent at
      dose rates >5000 mGy/h. Proliferation enhancement of irradiated cells compared
      with unirradiated controls occurs at both X-ray peak energies, but its magnitude
      is modulated by X-ray peak energy and cell melanization. At dose rates <5000
      mGy/h, both melanized and non-melanized cells exposed to 150 kVp X-rays, and non
      melanized cells exposed to 320 kVp X-rays, all exhibit the same proliferation
      enhancement: on average, chronic irradiation stimulates each founder cell to
      produce 100 (95% CI: 83, 116) extra descendants over 48 hours. Interactions
      between melanin and 320 kVp X-rays result in a significant (2-tailed p-value =
      4.8 * 10(-5)) additional increase in the number of radiation-induced descendants
      per founder cell: by 55 (95% CI: 29, 81). These results show that both melanin
      dependent and melanin-independent mechanisms are involved in radiation-induced
      fungal growth enhancement, and implicate direct and/or indirect interactions of
      melanin with high energy ionizing photons as an important pro-proliferative
      factor.

PMID- 24454888
TI  - Developmental dysplasia of the hip, age, BMI, place of residence and tobacco
      abuse increase the odds of aseptic loosening in Chinese patients.
AB  - PURPOSE: The purpose of this hospital-based case-control study was to evaluate
      the patient-related risk factors for aseptic loosening after total hip
      arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients.
      METHODS: From January 2000 to December 2012, 67 patients undergoing THA and TKA
      who developed aseptic loosening were detected as case subjects and 336 patients
      without aseptic loosening, matched by the year of index surgery and type of
      surgery, were selected as controls. Conditional logistic regression was used to
      compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The
      demographic factors and comorbid conditions associated with a risk-adjusted
      increase in aseptic loosening (in decreasing order of significance) were a rural
      place of residence (OR = 2.28; 95% CI: 1.21-4.30; p = 0.011), body mass index
      (BMI) >= 28 kg/m(2) (vs. 18.5-28 kg/m(2)) (OR = 2.29; 95% CI: 1.19-4.41; p =
      0.013), developmental dysplasia of the hip (DDH) (OR = 2.91; 95% CI: 1.11-7.66; p
      = 0.030), tobacco abuse (OR = 2.88; 95% CI: 1.05-7.89; p = 0.039), and age <45
      years (vs. 45-65 years) (OR = 2.63; 95% CI: 1.01-6.80; p = 0.047). CONCLUSIONS:
      Patients aged <45 years and those with a BMI of >= 28 kg/m(2), a preoperative
      diagnosis of DDH, history of tobacco abuse, or living in rural areas are at
      increased risk for aseptic loosening after THA and TKA in Chinese population.
      Additional systematic large-scale studies are needed to verify these results.

PMID- 24454889
TI  - Novel method to load multiple genes onto a mammalian artificial chromosome.
AB  - Mammalian artificial chromosomes are natural chromosome-based vectors that may
      carry a vast amount of genetic material in terms of both size and number. They
      are reasonably stable and segregate well in both mitosis and meiosis. A platform
      artificial chromosome expression system (ACEs) was earlier described with
      multiple loading sites for a modified lambda-integrase enzyme. It has been shown
      that this ACEs is suitable for high-level industrial protein production and the
      treatment of a mouse model for a devastating human disorder, Krabbe's disease.
      ACEs-treated mutant mice carrying a therapeutic gene lived more than four times
      longer than untreated counterparts. This novel gene therapy method is called
      combined mammalian artificial chromosome-stem cell therapy. At present, this
      method suffers from the limitation that a new selection marker gene should be
      present for each therapeutic gene loaded onto the ACEs. Complex diseases require
      the cooperative action of several genes for treatment, but only a limited number
      of selection marker genes are available and there is also a risk of serious side
      effects caused by the unwanted expression of these marker genes in mammalian
      cells, organs and organisms. We describe here a novel method to load multiple
      genes onto the ACEs by using only two selectable marker genes. These markers may
      be removed from the ACEs before therapeutic application. This novel technology
      could revolutionize gene therapeutic applications targeting the treatment of
      complex disorders and cancers. It could also speed up cell therapy by allowing
      researchers to engineer a chromosome with a predetermined set of genetic factors
      to differentiate adult stem cells, embryonic stem cells and induced pluripotent
      stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool
      for the investigation of complex biochemical pathways in basic science by
      producing an ACEs with several genes from a signal transduction pathway of
      interest. 

PMID- 24454890
TI  - Transcriptional profiling of whole blood identifies a unique 5-gene signature for
      myelofibrosis and imminent myelofibrosis transformation.
AB  - Identifying a distinct gene signature for myelofibrosis may yield novel
      information of the genes, which are responsible for progression of essential
      thrombocythemia and polycythemia vera towards myelofibrosis. We aimed at
      identifying a simple gene signature - composed of a few genes - which were
      selectively and highly deregulated in myelofibrosis patients. Gene expression
      microarray studies have been performed on whole blood from 69 patients with
      myeloproliferative neoplasms. Amongst the top-20 of the most upregulated genes in
      PMF compared to controls, we identified 5 genes (DEFA4, ELA2, OLFM4, CTSG, and
      AZU1), which were highly significantly deregulated in PMF only. None of these
      genes were significantly regulated in ET and PV patients. However, hierarchical
      cluster analysis showed that these genes were also highly expressed in a subset
      of patients with ET (n = 1) and PV (n = 4) transforming towards myelofibrosis
      and/or being featured by an aggressive phenotype. We have identified a simple 5
      gene signature, which is uniquely and highly significantly deregulated in
      patients in transitional stages of ET and PV towards myelofibrosis and in
      patients with PMF only. Some of these genes are considered to be responsible for
      the derangement of bone marrow stroma in myelofibrosis. Accordingly, this gene
      signature may reflect key processes in the pathogenesis and pathophysiology of
      myelofibrosis development. 

PMID- 24454891
TI  - A three-dimensional analysis of morphological evolution and locomotor performance
      of the carnivoran forelimb.
AB  - In this study, three-dimensional landmark-based methods of geometric
      morphometrics are used for estimating the influence of phylogeny, allometry and
      locomotor performance on forelimb shape in living and extinct carnivorans
      (Mammalia, Carnivora). The main objective is to investigate morphological
      convergences towards similar locomotor strategies in the shape of the major
      forelimb bones. Results indicate that both size and phylogeny have strong effects
      on the anatomy of all forelimb bones. In contrast, bone shape does not correlate
      in the living taxa with maximum running speed or daily movement distance, two
      proxies closely related to locomotor performance. A phylomorphospace approach
      showed that shape variation in forelimb bones mainly relates to changes in bone
      robustness. This indicates the presence of biomechanical constraints resulting
      from opposite demands for energetic efficiency in locomotion -which would require
      a slender forelimb- and resistance to stress -which would be satisfied by a
      robust forelimb-. Thus, we interpret that the need of maintaining a trade-off
      between both functional demands would limit shape variability in forelimb bones.
      Given that different situations can lead to one or another morphological
      solution, depending on the specific ecology of taxa, the evolution of forelimb
      morphology represents a remarkable "one-to-many mapping" case between anatomy and
      ecology. 

PMID- 24454892
TI  - Molecular cloning and characterization of growth factor receptor bound-protein in
      Clonorchis sinensis.
AB  - BACKGROUND: Clonorchis sinensis causes clonorchiasis, a potentially serious
      disease. Growth factor receptor-bound protein 2 (Grb2) is a cytosolic protein
      conserved among animals and plays roles in cellular functions such as meiosis,
      organogenesis and energy metabolism. In the present study, we report first
      molecular characters of growth factor receptor bound-protein (CsGrb2) from C.
      sinensis as counter part of Grb2 from animals and its possible functions in
      development and organogenesis of C. sinensis. METHODOLOGY/PRINCIPAL FINDINGS: A
      CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a
      polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially
      produced and purified to homogeneity. Native CsGrb2 with estimated molecular
      weight was identified from C. sinensis adult extract by western blotting using a
      mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in
      the metacercariae than in the adults. Immunohistochemical staining showed that
      CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal
      receptacle and ovary in the adults, and abundantly expressed in most organs of
      the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a
      serodiagnostic reagent for C. sinesis human infections. CONCLUSION: Grb2 protein
      found in C. sinensis was conserved among animals and suggested to play a role in
      the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis.
      These findings from C. sinensis provide wider understanding on diverse function
      of Grb2 in lower animals such as platyhelminths.

PMID- 24454893
TI  - Impact of intramammary treatment on gene expression profiles in bovine
      Escherichia coli mastitis.
AB  - Clinical mastitis caused by E. coli accounts for significant production losses
      and animal welfare concerns on dairy farms worldwide. The benefits of therapeutic
      intervention in mild to moderate cases are incompletely understood. We
      investigated the effect of intramammary treatment with cefapirin alone or in
      combination with prednisolone on gene expression profiles in experimentally
      induced E. coli mastitis in six mid-lactating Holstein Friesian cows. Cows were
      challenged with E. coli in 3 quarters and received 4 doses of 300 mg cefapirin in
      one quarter and 4 doses of 300 mg cefapirin together with 20 mg prednisolone in
      another quarter. At 24 h (n = 3) or 48 h (n = 3) post-challenge, tissue samples
      from control and treated quarters were collected for microarray analysis. Gene
      expression analysis of challenged, un-treated quarters revealed an up-regulation
      of transcripts associated with immune response functions compared to un
      challenged quarters. Both treatments resulted in down-regulation of these
      transcripts compared to challenged, un-treated quarters most prominently for
      genes representing Chemokine and TLR-signaling pathways. Gene expression of
      Lipopolysaccharide Binding Protein (LBP), CCL2 and CXCL2 were only significantly
      down-regulated in cefapirin-prednisolone-treated quarters compared to un-treated
      controls. Down-regulation of chemokines was further confirmed on the basis of
      protein levels in milk whey for CXCL1, CXCL2 and CXCL8 in both treatments with a
      greater decrease in cefapirin-prednisolone-treated quarters. The data reveal a
      significant effect of treatment on cell recruitment with a more pronounced effect
      in cefapirin-prednisolone treated quarters. Provided a rapid bacteriological
      clearance, combination therapy may prevent neutrophil-induced tissue damage and
      promote recovery of the gland. 

PMID- 24454894
TI  - Detection of time-varying structures by large deformation diffeomorphic metric
      mapping to aid reading of high-resolution CT images of the lung.
AB  - OBJECTIVES: To evaluate the accuracy of advanced non-linear registration of
      serial lung Computed Tomography (CT) images using Large Deformation Diffeomorphic
      Metric Mapping (LDDMM). METHODS: FIFTEEN CASES OF LUNG CANCER WITH SERIAL LUNG CT
      IMAGES (INTERVAL: 62.2+/-26.9 days) were used. After affine transformation, three
      dimensional, non-linear volume registration was conducted using LDDMM with or
      without cascading elasticity control. Registration accuracy was evaluated by
      measuring the displacement of landmarks placed on vessel bifurcations for each
      lung segment. Subtraction images and Jacobian color maps, calculated from the
      transformation matrix derived from image warping, were generated, which were used
      to evaluate time-course changes of the tumors. RESULTS: The average displacement
      of landmarks was 0.02+/-0.16 mm and 0.12+/-0.60 mm for proximal and distal
      landmarks after LDDMM transformation with cascading elasticity control, which was
      significantly smaller than 3.11+/-2.47 mm and 3.99+/-3.05 mm, respectively, after
      affine transformation. Emerged or vanished nodules were visualized on subtraction
      images, and enlarging or shrinking nodules were displayed on Jacobian maps
      enabled by highly accurate registration of the nodules using LDDMM. However, some
      residual misalignments were observed, even with non-linear transformation when
      substantial changes existed between the image pairs. CONCLUSIONS: LDDMM provides
      accurate registration of serial lung CT images, and temporal subtraction images
      with Jacobian maps help radiologists to find changes in pulmonary nodules.

PMID- 24454896
TI  - Increased serum C-reactive protein level is associated with increased storage
      lower urinary tract symptoms in men with benign prostatic hyperplasia.
AB  - OBJECTIVE: Chronic inflammation is considered as one of the contributing
      mechanisms of lower urinary tract symptoms (LUTS). Serum C-reactive protein (CRP)
      level is the widely used biomarker of inflammatory status. This study
      investigated the association between serum CRP level in men with benign prostatic
      hyperplasia (BPH) and lower urinary tract symptoms (LUTS) before and after
      medical treatment. METHODS: A total of 853 men with BPH and LUTS were enrolled.
      All patients completed the International Prostate Symptoms Score (IPSS)
      questionnaire and urological examinations. The parameters of uroflowmetry
      (maximum flow rate, Qmax; voided volume, VV), post-void residual (PVR), total
      prostate volume (TPV) and transition zone index (TZI), serum prostate specific
      antigen (PSA), and serum CRP levels were obtained. All patients were treated with
      alpha-blocker or antimuscarinic agent based on the IPSS voiding to storage
      subscore ratio (IPSS-V/S). Correlation analyses were performed between serum CRP
      levels with age, IPSS, TPV, TZI, Qmax, PVR, VV, PSA and between baseline and post
      treatment. RESULTS: The mean age was 66.9 +/- 11.6 years old and the mean serum
      CRP levels were 0.31 +/- 0.43 mg/dL. Univariate analyses revealed serum CRP
      levels were significantly associated with age (p<0.001), PSA levels (p = 0.005)
      and VV (p = 0.017), but not significantly associated with TPV (p = 0.854) or PVR
      (p = 0.068). CRP levels were positively associated with urgency (p<0.001) and
      nocturia (p<0.001) subscore of IPSS, total IPSS (p = 0.008) and storage IPSS
      (p<0.001) and negatively associated with IPSS- V/S ratio (p = 0.014).
      Multivariate analyses revealed that serum CRP levels were significantly
      associated with age (p = 0.004) and storage IPSS subscore p<0.001). Patients with
      IPSS-V/S<1 and treated with tolterodine for 3 months had significant decrease of
      CRP levels after treatment. CONCLUSION: Serum CRP levels are associated with
      storage LUTS and sensory bladder disorders, suggesting chronic inflammation might
      play a role in the patients with storage predominant LUTS.

PMID- 24454895
TI  - A flagellin-derived toll-like receptor 5 agonist stimulates cytotoxic lymphocyte
      mediated tumor immunity.
AB  - Toll-like receptor (TLR) mediated recognition of pathogen associated molecular
      patterns allows the immune system to rapidly respond to a pathogenic insult. The
      "danger context" elicited by TLR agonists allows an initially non-immunogenic
      antigen to become immunogenic. This ability to alter environment is highly
      relevant in tumor immunity, since it is inherently difficult for the immune
      system to recognize host-derived tumors as immunogenic. However, immune cells may
      have encountered certain TLR ligands associated with tumor development, yet the
      endogenous stimulation is typically not sufficient to induce spontaneous tumor
      rejection. Of special interest are TLR5 agonists, because there are no endogenous
      ligands that bind TLR5. CBLB502 is a pharmacologically optimized TLR5 agonist
      derived from Salmonella enterica flagellin. We examined the effect of CBLB502 on
      tumor immunity using two syngeneic lymphoma models, both of which do not express
      TLR5, and thus do not directly respond to CBLB502. Upon challenge with the T-cell
      lymphoma RMAS, CBLB502 treatment after tumor inoculation protects C57BL/6 mice
      from death caused by tumor growth. This protective effect is both natural killer
      (NK) cell- and perforin-dependent. In addition, CBLB502 stimulates clearance of
      the B-cell lymphoma A20 in BALB/c mice in a CD8(+) T cell-dependent fashion.
      Analysis on the cellular level via ImageStream flow cytometry reveals that
      CD11b(+) and CD11c(+) cells, but neither NK nor T cells, directly respond to
      CBLB502 as determined by NFkappaB nuclear translocation. Our findings demonstrate
      that CBLB502 stimulates a robust antitumor response by directly activating TLR5
      expressing accessory immune cells, which in turn activate cytotoxic lymphocytes. 

PMID- 24454897
TI  - Wildlife reservoirs of canine distemper virus resulted in a major outbreak in
      Danish farmed mink (Neovison vison).
AB  - A major outbreak of canine distemper virus (CDV) in Danish farmed mink (Neovison
      vison) started in the late summer period of 2012. At the same time, a high number
      of diseased and dead wildlife species such as foxes, raccoon dogs, and ferrets
      were observed. To track the origin of the outbreak virus full-length sequencing
      of the receptor binding surface protein hemagglutinin (H) was performed on 26
      CDV's collected from mink and 10 CDV's collected from wildlife species.
      Subsequent phylogenetic analyses showed that the virus circulating in the mink
      farms and wildlife were highly identical with an identity at the nucleotide level
      of 99.45% to 100%. The sequences could be grouped by single nucleotide
      polymorphisms according to geographical distribution of mink farms and wildlife.
      The signaling lymphocytic activation molecule (SLAM) receptor binding region in
      most viruses from both mink and wildlife contained G at position 530 and Y at
      position 549; however, three mink viruses had an Y549H substitution. The outbreak
      viruses clustered phylogenetically in the European lineage and were highly
      identical to wildlife viruses from Germany and Hungary (99.29% - 99.62%). The
      study furthermore revealed that fleas (Ceratophyllus sciurorum) contained CDV and
      that vertical transmission of CDV occurred in a wild ferret. The study provides
      evidence that wildlife species, such as foxes, play an important role in the
      transmission of CDV to farmed mink and that the virus may be maintained in the
      wild animal reservoir between outbreaks. 

PMID- 24454899
TI  - Comparison of the sequence-dependent fluorescence of the cyanine dyes Cy3, Cy5,
      DyLight DY547 and DyLight DY647 on single-stranded DNA.
AB  - Cyanine dyes are commonly used for fluorescent labeling of DNA and RNA
      oligonucleotides in applications including qPCR, sequencing, fluorescence in situ
      hybridization, Forster resonance energy transfer, and labeling for microarray
      hybridization. Previous research has shown that the fluorescence efficiency of
      Cy3 and Cy5, covalently attached to the 5' end of single-stranded DNA, is
      strongly sequence dependent. Here, we show that DY547 and DY647, two alternative
      cyanine dyes that are becoming widely used for nucleic acid labeling, have a
      similar pattern of sequence-dependence, with adjacent purines resulting in higher
      intensity and adjacent cytosines resulting in lower intensity. Investigated over
      the range of all 1024 possible DNA 5mers, the intensities of Cy3 and Cy5 drop by
      ~ 50% and ~ 65% with respect to their maxima, respectively, whereas the
      intensities of DY547 and DY647 fall by ~ 45% and ~ 40%, respectively. The reduced
      magnitude of change of the fluorescence intensity of the DyLight dyes,
      particularly of DY647 in comparison with Cy5, suggests that these dyes are less
      likely to introduce sequence-dependent bias into experiments based on fluorescent
      labeling of nucleic acids.

PMID- 24454898
TI  - Identification of critical regions and candidate genes for cardiovascular
      malformations and cardiomyopathy associated with deletions of chromosome 1p36.
AB  - Cardiovascular malformations and cardiomyopathy are among the most common
      phenotypes caused by deletions of chromosome 1p36 which affect approximately 1 in
      5000 newborns. Although these cardiac-related abnormalities are a significant
      source of morbidity and mortality associated with 1p36 deletions, most of the
      individual genes that contribute to these conditions have yet to be identified.
      In this paper, we use a combination of clinical and molecular cytogenetic data to
      define five critical regions for cardiovascular malformations and two critical
      regions for cardiomyopathy on chromosome 1p36. Positional candidate genes which
      may contribute to the development of cardiovascular malformations associated with
      1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1,
      and WASF2. Similarly, haploinsufficiency of PRDM16-a gene which was recently
      shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ,
      RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy. When
      treating individuals with 1p36 deletions, or providing prognostic information to
      their families, physicians should take into account that 1p36 deletions which
      overlie these cardiac critical regions may portend to cardiovascular
      complications. Since several of these cardiac critical regions contain more than
      one positional candidate gene-and large terminal and interstitial 1p36 deletions
      often overlap more than one cardiac critical region-it is likely that
      haploinsufficiency of two or more genes contributes to the cardiac phenotypes
      associated with many 1p36 deletions. 

PMID- 24454900
TI  - Tuberculosis contact investigation using interferon-gamma release assay with
      chest x-ray and computed tomography.
AB  - Between September 2009 and January 2010, 6 members of the Japanese Eastern Army,
      who had completed the same training program, were diagnosed with active
      tuberculosis (TB) on different occasions. The Ministry of Defense conducted a
      contact investigation of all members who had come into contact with the infected
      members. The purpose of this study was to verify the efficacy of the TB screening
      protocol used in this investigation. A total of 884 subjects underwent interferon
      gamma release assay (IGRA) and chest X-ray. The 132 subjects who were IGRA
      positive or with X-ray findings suggestive of TB subsequently underwent chest
      computer tomography (CT). Chest CT was performed for 132 subjects. Based on CT
      findings, 24 (2.7%) subjects were classified into the active TB group, 107
      (12.1%) into the latent tuberculosis infection (LTBI) group, and 753 (85.2%) into
      the non-TB group. The first 2 groups underwent anti-TB therapy, and all 3 groups
      were followed for 2 years after treatment. Although one subject in the active TB
      group experienced relapse during the follow-up period, no patient in the LTBI or
      non-TB groups developed TB. IGRA and chest X-ray, followed by chest CT for those
      IGRA positive or with suspicious X-ray findings, appears to be an effective means
      of TB contact screening and infection prevention. 

PMID- 24454901
TI  - Unique behavioral characteristics and microRNA signatures in a drug resistant
      epilepsy model.
AB  - BACKGROUND: Pharmacoresistance is a major issue in the treatment of epilepsy.
      However, the mechanism underlying pharmacoresistance to antiepileptic drugs
      (AEDs) is still unclear, and few animal models have been established for studying
      drug resistant epilepsy (DRE). In our study, spontaneous recurrent seizures
      (SRSs) were investigated by video-EEG monitoring during the entire procedure.
      METHODS/PRINCIPAL FINDINGS: In the mouse pilocarpine-induced epilepsy model, we
      administered levetiracetam (LEV) and valproate (VPA) in sequence. AED-responsive
      and AED-resistant mice were naturally selected after 7-day treatment of LEV and
      VPA. Behavioral tests (open field, object exploration, elevated plus maze, and
      light-dark transition test) and a microRNA microarray test were performed. Among
      the 37 epileptic mice with SRS, 23 showed significantly fewer SRSs during
      administration of LEV (n = 16, LEV sensitive (LS) group) or VPA (n = 7, LEV
      resistant/VPA sensitive (LRVS) group), while 7 epileptic mice did not show any
      amelioration with either of the AEDs (n = 7, multidrug resistant (MDR) group). On
      the behavioral assessment, MDR mice displayed distinctive behaviors in the object
      exploration and elevated plus maze tests, which were not observed in the LS
      group. Expression of miRNA was altered in LS and MDR groups, and we identified 4
      miRNAs (miR-206, miR-374, miR-468, and miR-142-5p), which were differently
      modulated in the MDR group versus both control and LS groups. CONCLUSION: This is
      the first study to identify a pharmacoresistant subgroup, resistant to 2 AEDs, in
      the pilocarpine-induced epilepsy model. We hypothesize that modulation of the
      identified miRNAs may play a key role in developing pharmacoresistance and
      behavioral alterations in the MDR group.

PMID- 24454902
TI  - Tumor-specific hypermethylation of epigenetic biomarkers, including SFRP1,
      predicts for poorer survival in patients from the TCGA Kidney Renal Clear Cell
      Carcinoma (KIRC) project.
AB  - The recent publication of the TCGA Kidney Renal Clear Cell Carcinoma (KIRC)
      project has provided an immense wealth and breadth of data providing an
      invaluable tool for confirmation and expansion upon previous observations in a
      large data set containing multiple data types including DNA methylation, somatic
      mutation, and clinical information. In clear cell renal cell carcinoma (CCRCC)
      many genes have been demonstrated to be epigenetically inactivated by promoter
      hypermethylated and in a small number of cases to be associated with clinical
      outcome. This study created two cohorts based on the Illumina BeadChip array used
      to confirm the frequency of tumor-specific hypermethylation of these published
      hypermethylated genes, assess the impact of somatic mutation or chromosomal loss
      and provide the most comprehensive assessment to date of the association of this
      hypermethylation with patient survival. Hypermethylation of the Fibrillin 2
      (FBN2) gene was the most consistent epigenetic biomarker for CCRCC across both
      cohorts in 40.2% or 52.5% of tumors respectively. Hypermethylation of the
      secreted frizzled-related protein 1 (SFRP1) gene and the basonuclin 1 (BNC1) gene
      were both statistically associated with poorer survival in both cohorts (SFRP1 -
      p = <0.0001 or 0.0010 and BNC1 - p = <0.0001 or 0.0380) and represented better
      independent markers of survival than tumor stage, grade or dimension in one
      cohort and tumor stage or dimension in the other cohort. Loss of the SFRP1
      protein can potentially activate the WNT pathway and this analysis highlighted
      hypermethylation of several other WNT pathway regulating genes and demonstrated a
      poorer survival outcome for patients with somatic mutation of these genes. The
      success of demethylating drugs in hematological malignances and the current
      trials in solid tumors suggest that the identification of clinically relevant
      hypermethylated genes combined with therapeutic advances may improve the
      effectiveness and usefulness of such drugs in clear cell renal cell carcinoma.

PMID- 24454903
TI  - Unravelling the diversity of grapevine microbiome.
AB  - Vitis vinifera is one of the most widely cultivated fruit crops with a great
      economic impact on the global industry. As a plant, it is naturally colonised by
      a wide variety of both prokaryotic and eukaryotic microorganisms that interact
      with grapevine, having either beneficial or phytopathogenic effects, who play a
      major role in fruit yield, grape quality and, ultimately, in the evolution of
      grape fermentation and wine production. Therefore, the objective of this study
      was to extensively characterize the natural microbiome of grapevine. Considering
      that the majority of microorganisms are uncultivable, we have deeply studied the
      microflora of grapevine leaves using massive parallel rDNA sequencing, along its
      vegetative cycle. Among eukaryotic population the most abundant microorganisms
      belonged to the early diverging fungi lineages and Ascomycota phylum, whereas the
      Basidiomycota were the least abundant. Regarding prokaryotes, a high diversity of
      Proteobacteria, Firmicutes and Actinobacteria was unveiled. Indeed, the microbial
      communities present in the vineyard during its vegetative cycle were shown to be
      highly structured and dynamic. In all cases, the major abundant microorganisms
      were the yeast-like fungus Aureobasidium and the prokaryotic Enterobacteriaceae.
      Herein, we report the first complete microbiome landscape of the vineyard,
      through a metagenomic approach, and highlight the analysis of the microbial
      interactions within the vineyard and its importance for the equilibrium of the
      microecosystem of grapevines. 

PMID- 24454904
TI  - Flagellin treatment prevents increased susceptibility to systemic bacterial
      infection after injury by inhibiting anti-inflammatory IL-10+ IL-12- neutrophil
      polarization.
AB  - Severe trauma renders patients susceptible to infection. In sepsis, defective
      bacterial clearance has been linked to specific deviations in the innate immune
      response. We hypothesized that innate immune modulations observed during sepsis
      also contribute to increased bacterial susceptibility after severe trauma. A well
      established murine model of burn injury, used to replicate infection following
      trauma, showed that wound inoculation with P. aeruginosa quickly spreads
      systemically. The systemic IL-10/IL-12 axis was skewed after burn injury with
      infection as indicated by a significant elevation in serum IL-10 and polarization
      of neutrophils into an anti-inflammatory ("N2"; IL-10(+) IL-12(-)) phenotype.
      Infection with an attenuated P. aeruginosa strain (DeltaCyaB) was cleared better
      than the wildtype strain and was associated with an increased pro-inflammatory
      neutrophil ("N1"; IL-10(-)IL-12(+)) response in burn mice. This suggests that
      neutrophil polarization influences bacterial clearance after burn injury.
      Administration of a TLR5 agonist, flagellin, after burn injury restored the
      neutrophil response towards a N1 phenotype resulting in an increased clearance of
      wildtype P. aeruginosa after wound inoculation. This study details specific
      alterations in innate cell populations after burn injury that contribute to
      increased susceptibility to bacterial infection. In addition, for the first time,
      it identifies neutrophil polarization as a therapeutic target for the reversal of
      bacterial susceptibility after injury. 

PMID- 24454905
TI  - The RNA chaperone Hfq is involved in stress tolerance and virulence in
      uropathogenic Proteus mirabilis.
AB  - Hfq is a bacterial RNA chaperone involved in the riboregulation of diverse genes
      via small noncoding RNAs. Here, we show that Hfq is critical for the
      uropathogenic Proteus mirabilis to effectively colonize the bladder and kidneys
      in a murine urinary tract infection (UTI) model and to establish burned wound
      infection of the rats. In this regard, we found the hfq mutant induced higher IL
      8 and MIF levels of uroepithelial cells and displayed reduced intra-macrophage
      survival. The loss of hfq affected bacterial abilities to handle H2O2 and osmotic
      pressures and to grow at 50  degrees C. Relative to wild-type, the hfq mutant had
      reduced motility, fewer flagella and less hemolysin expression and was less prone
      to form biofilm and to adhere to and invade uroepithelial cells. The MR/P
      fimbrial operon was almost switched to the off phase in the hfq mutant. In
      addition, we found the hfq mutant exhibited an altered outer membrane profile and
      had higher RpoE expression, which indicates the hfq mutant may encounter
      increased envelope stress. With the notion of envelope disturbance in the hfq
      mutant, we found increased membrane permeability and antibiotic susceptibilities
      in the hfq mutant. Finally, we showed that Hfq positively regulated the RpoS
      level and tolerance to H2O2 in the stationary phase seemed largely mediated
      through the Hfq-dependent RpoS expression. Together, our data indicate that Hfq
      plays a critical role in P. mirabilis to establish UTIs by modulating stress
      responses, surface structures and virulence factors. This study suggests Hfq may
      serve as a scaffold molecule for development of novel anti-P. mirabilis drugs and
      P. mirabilis hfq mutant is a vaccine candidate for preventing UTIs.

PMID- 24454906
TI  - Seasonal survival probabilities suggest low migration mortality in migrating
      bats.
AB  - Migration is adaptive if survival benefits are larger than costs of residency.
      Many aspects of bat migration ecology such as migratory costs, stopover site use
      and fidelity are largely unknown. Since many migrating bats are endangered, such
      information is urgently needed to promote conservation. We selected the migrating
      Leisler's bat (Nyctalus leisleri) as model species and collected capture
      recapture data in southern Switzerland year round during 6 years. We estimated
      seasonal survival and site fidelity with Cormack-Jolly-Seber models that
      accounted for the presence of transients fitted with Bayesian methods and
      assessed differences between sexes and seasons. Activity peaked in autumn and
      spring, whereas very few individuals were caught during summer. We hypothesize
      that the study site is a migratory stopover site used during fall and spring
      migration for most individuals, but there is also evidence for wintering.
      Additionally, we found strong clues for mating during fall. Summer survival that
      included two major migratory journeys was identical to winter survival in males
      and slightly higher in females, suggesting that the migratory journeys did not
      bear significant costs in terms of survival. Transience probability was in both
      seasons higher in males than in females. Our results suggest that, similarly to
      birds, Leisler's bat also use stopover sites during migration with high site
      fidelity. In contrast to most birds, the stopover site was also used for mating
      and migratory costs in terms of survival seemed to be low. Transients' analyses
      highlighted strong individual variation in site use which makes particularly
      challenging the study and modelling of their populations as well as their
      conservation. 

PMID- 24454907
TI  - Mutation and selection cause codon usage and bias in mitochondrial genomes of
      ribbon worms (Nemertea).
AB  - The phenomenon of codon usage bias is known to exist in many genomes and it is
      mainly determined by mutation and selection. To understand the patterns of codon
      usage in nemertean mitochondrial genomes, we use bioinformatic approaches to
      analyze the protein-coding sequences of eight nemertean species. Neutrality
      analysis did not find a significant correlation between GC12 and GC3. ENc-plot
      showed a few genes on or close to the expected curve, but the majority of points
      with low-ENc values are below it. ENc-plot suggested that mutational bias plays a
      major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed
      that GC and AT were not used proportionally and we propose that codons containing
      A or U at third position are used preferentially in nemertean species, regardless
      of whether corresponding tRNAs are encoded in the mitochondrial DNA. Context
      dependent analysis indicated that the nucleotide at the second codon position
      slightly affects synonymous codon choices. These results suggested that
      mutational and selection forces are probably acting to codon usage bias in
      nemertean mitochondrial genomes. 

PMID- 24454908
TI  - Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3.
AB  - We have previously reported that the expression of mitochondrial deacetylase
      SIRT3 is high in the slow oxidative muscle and that the expression of muscle
      SIRT3 level is increased by dietary restriction or exercise training. To explore
      the function of SIRT3 in skeletal muscle, we report here the establishment of a
      transgenic mouse model with muscle-specific expression of the murine SIRT3 short
      isoform (SIRT3M3). Calorimetry study revealed that the transgenic mice had
      increased energy expenditure and lower respiratory exchange rate (RER),
      indicating a shift towards lipid oxidation for fuel usage, compared to control
      mice. The transgenic mice exhibited better exercise performance on treadmills,
      running 45% further than control animals. Moreover, the transgenic mice displayed
      higher proportion of slow oxidative muscle fibers, with increased muscle AMPK
      activation and PPARdelta expression, both of which are known regulators promoting
      type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3
      reduced muscle mass up to 30%, likely through an up-regulation of FOXO1
      transcription factor and its downstream atrophy gene MuRF-1. In summary, these
      results suggest that SIRT3 regulates the formation of oxidative muscle fiber,
      improves muscle metabolic function, and reduces muscle mass, changes that mimic
      the effects of caloric restriction. 

PMID- 24454909
TI  - Spatiotemporal imaging of glutamate-induced biophotonic activities and
      transmission in neural circuits.
AB  - The processing of neural information in neural circuits plays key roles in neural
      functions. Biophotons, also called ultra-weak photon emissions (UPE), may play
      potential roles in neural signal transmission, contributing to the understanding
      of the high functions of nervous system such as vision, learning and memory,
      cognition and consciousness. However, the experimental analysis of biophotonic
      activities (emissions) in neural circuits has been hampered due to technical
      limitations. Here by developing and optimizing an in vitro biophoton imaging
      method, we characterize the spatiotemporal biophotonic activities and
      transmission in mouse brain slices. We show that the long-lasting application of
      glutamate to coronal brain slices produces a gradual and significant increase of
      biophotonic activities and achieves the maximal effect within approximately 90
      min, which then lasts for a relatively long time (>200 min). The initiation
      and/or maintenance of biophotonic activities by glutamate can be significantly
      blocked by oxygen and glucose deprivation, together with the application of a
      cytochrome c oxidase inhibitor (sodium azide), but only partly by an action
      potential inhibitor (TTX), an anesthetic (procaine), or the removal of
      intracellular and extracellular Ca(2+). We also show that the detected
      biophotonic activities in the corpus callosum and thalamus in sagittal brain
      slices mostly originate from axons or axonal terminals of cortical projection
      neurons, and that the hyperphosphorylation of microtubule-associated protein tau
      leads to a significant decrease of biophotonic activities in these two areas.
      Furthermore, the application of glutamate in the hippocampal dentate gyrus
      results in increased biophotonic activities in its intrahippocampal projection
      areas. These results suggest that the glutamate-induced biophotonic activities
      reflect biophotonic transmission along the axons and in neural circuits, which
      may be a new mechanism for the processing of neural information. 

PMID- 24454910
TI  - Softenin, a novel protein that softens the connective tissue of sea cucumbers
      through inhibiting interaction between collagen fibrils.
AB  - The dermis in the holothurian body wall is a typical catch connective tissue or
      mutable collagenous tissue that shows rapid changes in stiffness. Some chemical
      factors that change the stiffness of the tissue were found in previous studies,
      but the molecular mechanisms of the changes are not yet fully understood.
      Detection of factors that change the stiffness by working directly on the
      extracellular matrix was vital to clarify the mechanisms of the change. We
      isolated from the body wall of the sea cucumber Stichopus chloronotus a novel
      protein, softenin, that softened the body-wall dermis. The apparent molecular
      mass was 20 kDa. The N-terminal sequence of 17 amino acids had low homology to
      that of known proteins. We performed sequential chemical and physical dissections
      of the dermis and tested the effects of softenin on each dissection stage by
      dynamic mechanical tests. Softenin softened Triton-treated dermis whose cells had
      been disrupted by detergent. The Triton-treated dermis was subjected to
      repetitive freeze-and-thawing to make Triton-Freeze-Thaw (TFT) dermis that was
      softer than the Triton-treated dermis, implying that some force-bearing structure
      had been disrupted by this treatment. TFT dermis was stiffened by tensilin, a
      stiffening protein of sea cucumbers. Softenin softened the tensilin-stiffened TFT
      dermis while it had no effect on the TFT dermis without tensilin treatment. We
      isolated collagen from the dermis. When tensilin was applied to the suspending
      solution of collagen fibrils, they made a large compact aggregate that was
      dissolved by the application of softenin or by repetitive freeze-and-thawing.
      These results strongly suggested that softenin decreased dermal stiffness through
      inhibiting cross-bridge formation between collagen fibrils; the formation was
      augmented by tensilin and the bridges were broken by the freeze-thaw treatment.
      Softenin is thus the first softener of catch connective tissue shown to work on
      the cross-bridges between extracellular materials. 

PMID- 24454911
TI  - Analysis of novel NEFL mRNA targeting microRNAs in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by
      progressive motor neuron degeneration and neurofilament aggregate formation.
      Spinal motor neurons in ALS also show a selective suppression in the levels of
      low molecular weight neurofilament (NEFL) mRNA. We have been interested in
      investigating the role of microRNAs (miRNAs) in NEFL transcript stability. MiRNAs
      are small, 20-25 nucleotide, non-coding RNAs that act as post-transcriptional
      gene regulators by targeting the 3' untranslated region (3'UTR) of mRNA resulting
      in mRNA decay or translational silencing. In this study, we characterized
      putative novel miRNAs from a small RNA library derived from control and sporadic
      ALS (sALS) spinal cords. We detected 80 putative novel miRNAs, 24 of which have
      miRNA response elements (MREs) within the NEFL mRNA 3'UTR. From this group, we
      determined by real-time PCR that 10 miRNAs were differentially expressed in sALS
      compared to controls. Functional analysis by reporter gene assay and relative
      quantitative RT-PCR showed that two novel miRNAs, miR-b1336 and miR-b2403, were
      downregulated in ALS spinal cord and that both stabilize NEFL mRNA. We confirmed
      the direct effect of these latter miRNAs using anit-miR-b1336 and anti-miR-b2403.
      These results demonstrate that the expression of two miRNAs (miRNAs miR-b1336 and
      miR-b2403) whose effect is to stabilize NEFL mRNA are down regulated in ALS, the
      net effect of which is predicted to contribute directly to the loss of NEFL
      steady state mRNA which is pathognomic of spinal motor neurons in ALS. 

PMID- 24454912
TI  - LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of
      airway remodelling in a murine model of chronic OVA-induced allergic airway
      disease.
AB  - BACKGROUND: Tumstatin is a segment of the collagen-IV protein that is markedly
      reduced in the airways of asthmatics. Tumstatin can play an important role in the
      development of airway remodelling associated with asthma due to its anti
      angiogenic properties. This study assessed the anti-angiogenic properties of
      smaller peptides derived from tumstatin, which contain the interface tumstatin
      uses to interact with the alphaVbeta3 integrin. METHODS: Primary human lung
      endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides
      and assessed for cell viability and tube formation in vitro. The impact of the
      anti-angiogenic properties on airways hyperresponsiveness (AHR) was then examined
      using a murine model of chronic OVA-induced allergic airways disease. RESULTS:
      The LF-15 and T7 peptides significantly reduced endothelial cell viability and
      attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had
      reduced total lung vascularity and AHR was attenuated compared to mice exposed to
      OVA alone. T3 peptides reduced cell viability but had no effect on any other
      parameters. CONCLUSION: The LF-15 and T7 peptides may be appropriate candidates
      for use as novel pharmacotherapies due to their small size and anti-angiogenic
      properties observed in vitro and in vivo.

PMID- 24454913
TI  - Hindlimb suspension and SPE-like radiation impairs clearance of bacterial
      infections.
AB  - A major risk of extended space travel is the combined effects of weightlessness
      and radiation exposure on the immune system. In this study, we used the hindlimb
      suspension model of microgravity that includes the other space stressors,
      situational and confinement stress and alterations in food intake, and solar
      particle event (SPE)-like radiation to measure the combined effects on the
      ability to control bacterial infections. A massive increase in morbidity and
      decrease in the ability to control bacterial growth was observed using 2
      different types of bacteria delivered by systemic and pulmonary routes in 3
      different strains of mice. These data suggest that an astronaut exposed to a
      strong SPE during extended space travel is at increased risk for the development
      of infections that could potentially be severe and interfere with mission success
      and astronaut health. 

PMID- 24454914
TI  - An analysis of 1256 cases of sporadic ruptured cerebral aneurysm in a single
      Chinese institution.
AB  - BACKGROUND: To review the epidemiology of sporadic ruptured cerebral aneurysm.
      METHODS: This is a retrospective study of consecutive 1256 Chinese patients
      between January 2006 and January 2013, who were admitted to the Second Hospital
      of Hebei Medical University, China, for spontaneous subarachnoid hemorrhage due
      to a rupture of cerebral artery aneurysm. In 288 males and 478 females, the size
      of aneurysms was measured by a neuroradiologist on DSA. In 123 males and 184
      females, the size of the ruptured aneurysms was not measured. The remaining
      patients, with 61 males and 122 females, had multiple aneurysms, and the medical
      record could not reliably determine the specific aneurysm responsible for the
      rupture. RESULTS: In total there were 784 females and 472 males with a
      female/male ratio of 1.66. The female/male ratio was down to 0.50 for patients
      younger than 35 yrs. For both males and females, aneurysm rupture was most common
      during the age of 50-59 yrs. Ruptured aneurysms were mostly of 2 mm-5 mm in size
      (47.1%), followed by 5 mm-10 mm (39.7%). Ruptured single cerebral aneurysm
      occurred in anterior circulation in 95.0% of the cases, with 5.0% occurred in
      posterior circulation. Ruptured aneurysm most commonly occurred at posterior
      communicating artery (34.9%) and anterior communicating artery (29.5%). 183 cases
      (14.6%) had multiple aneurysms. CONCLUSIONS: With younger patients, there is a
      male predominance in our series. Ninety percent of patients have ruptured
      aneurysms less than 10 mm in size.

PMID- 24454915
TI  - Modifications in rat plasma proteome after remote ischemic preconditioning (RIPC)
      stimulus: identification by a SELDI-TOF-MS approach.
AB  - Remote ischemic preconditioning's (RIPC) ability to render the myocardium
      resistant to subsequent prolonged ischemia is now clearly established in
      different species, including humans. Strong evidence suggests that circulating
      humoral mediators play a key role in signal transduction, but their identities
      still need to be established. Our study sought to identify potential circulating
      RIPC mediators using a proteomic approach. Rats were exposed to 10-min limb
      ischemia followed by 5- (RIPC 5') or 10-min (RIPC 10') reperfusion prior to blood
      sampling. The control group only underwent blood sampling. Plasma samples were
      isolated for proteomic analysis using surface-enhanced laser desorption and
      ionization - time of flight - mass spectrometry (SELDI-TOF-MS). A total of seven
      proteins, including haptoglobin and transthyretin, were detected as up- or down
      regulated in response to RIPC. These proteins had previously been identified as
      associated with organ protection, anti-inflammation, and various cellular and
      molecular responses to ischemia. In conclusion, this study indicates that RIPC
      results in significant modulations of plasma proteome. 

PMID- 24454916
TI  - Rhythmic 24 h variation of core body temperature and locomotor activity in a
      subterranean rodent (Ctenomys aff. knighti), the tuco-tuco.
AB  - The tuco-tuco Ctenomys aff. knighti is a subterranean rodent which inhabits a
      semi-arid area in Northwestern Argentina. Although they live in underground
      burrows where environmental cycles are attenuated, they display robust, 24 h
      locomotor activity rhythms that are synchronized by light/dark cycles, both in
      laboratory and field conditions. The underground environment also poses energetic
      challenges (e.g. high-energy demands of digging, hypoxia, high humidity, low food
      availability) that have motivated thermoregulation studies in several
      subterranean rodent species. By using chronobiological protocols, the present
      work aims to contribute towards these studies by exploring day-night variations
      of thermoregulatory functions in tuco-tucos, starting with body temperature and
      its temporal relationship to locomotor activity. Animals showed daily, 24 h body
      temperature rhythms that persisted even in constant darkness and temperature,
      synchronizing to a daily light/dark cycle, with highest values occurring during
      darkness hours. The range of oscillation of body temperature was slightly lower
      than those reported for similar-sized and dark-active rodents. Most rhythmic
      parameters, such as period and phase, did not change upon removal of the running
      wheel. Body temperature and locomotor activity rhythms were robustly associated
      in time. The former persisted even after removal of the acute effects of intense
      activity on body temperature by a statistical method. Finally, regression
      gradients between body temperature and activity were higher in the beginning of
      the night, suggesting day-night variation in thermal conductance and heat
      production. Consideration of these day-night variations in thermoregulatory
      processes is beneficial for further studies on thermoregulation and energetics of
      subterranean rodents. 

PMID- 24454917
TI  - Optimizing viable leukocyte sampling from the female genital tract for clinical
      trials: an international multi-site study.
AB  - BACKGROUND: Functional analysis of mononuclear leukocytes in the female genital
      mucosa is essential for understanding the immunologic effects of HIV vaccines and
      microbicides at the site of HIV exposure. However, the best female genital tract
      sampling technique is unclear. METHODS AND FINDINGS: We enrolled women from four
      sites in Africa and the US to compare three genital leukocyte sampling methods:
      cervicovaginal lavages (CVL), endocervical cytobrushes, and ectocervical
      biopsies. Absolute yields of mononuclear leukocyte subpopulations were determined
      by flow cytometric bead-based cell counting. Of the non-invasive sampling types,
      two combined sequential cytobrushes yielded significantly more viable mononuclear
      leukocytes than a CVL (p<0.0001). In a subsequent comparison, two cytobrushes
      yielded as many leukocytes (~ 10,000) as one biopsy, with macrophages/monocytes
      being more prominent in cytobrushes and T lymphocytes in biopsies. Sample yields
      were consistent between sites. In a subgroup analysis, we observed significant
      reproducibility between replicate same-day biopsies (r = 0.89, p = 0.0123).
      Visible red blood cells in cytobrushes increased leukocyte yields more than three
      fold (p = 0.0078), but did not change their subpopulation profile, indicating
      that these leukocytes were still largely derived from the mucosa and not
      peripheral blood. We also confirmed that many CD4(+) T cells in the female
      genital tract express the alpha4beta7 integrin, an HIV envelope-binding mucosal
      homing receptor. CONCLUSIONS: CVL sampling recovered the lowest number of viable
      mononuclear leukocytes. Two cervical cytobrushes yielded comparable total numbers
      of viable leukocytes to one biopsy, but cytobrushes and biopsies were biased
      toward macrophages and T lymphocytes, respectively. Our study also established
      the feasibility of obtaining consistent flow cytometric analyses of isolated
      genital cells from four study sites in the US and Africa. These data represent an
      important step towards implementing mucosal cell sampling in international
      clinical trials of HIV prevention.

PMID- 24454918
TI  - The application of root mean square electrocardiography (RMS ECG) for the
      detection of acquired and congenital long QT syndrome.
AB  - BACKGROUND: Precise measurement of the QT interval is often hampered by
      difficulty determining the end of the low amplitude T wave. Root mean square
      electrocardiography (RMS ECG) provides a novel alternative measure of ventricular
      repolarization. Experimental data have shown that the interval between the RMS
      ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action
      potential duration while the RMS T wave width (TW) tracks the dispersion of
      repolarization timing. Here, we tested the precision of RMS ECG to assess
      ventricular repolarization in humans in the setting of drug-induced and
      congenital Long QT Syndrome (LQTS). METHODS: RMS ECG signals were derived from
      high-resolution 24 hour Holter monitor recordings from 68 subjects after
      receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97
      subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW
      intervals were automatically measured using custom software and compared to
      traditional QT measures using lead II. RESULTS: All measures of repolarization
      were prolonged during moxifloxacin administration and in LQTS subjects, but the
      variance of RMS intervals was significantly smaller than traditional lead II
      measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2,
      but not LQT-1 or LQT-3. CONCLUSION: These data validate the application of RMS
      ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements
      are more precise than the current standard of care lead II measurements.

PMID- 24454919
TI  - Puerarin attenuated early diabetic kidney injury through down-regulation of
      matrix metalloproteinase 9 in streptozotocin-induced diabetic rats.
AB  - Radix puerariae, a traditional Chinese herbal medication, has been used
      successfully to treat patients with early stage of diabetic nephropathy. However,
      the underlined mechanism of this renal protective effect has not been determined.
      In the current study, we investigated the effects and the mechanism of puerarin
      in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either
      puerarin or losartan, an angiotensin II receptor blocker, as compared to those
      treated with vehicle. We found that both puerarin and losartan attenuated kidney
      hypertrophy, mesangial expansion, proteinuria, and podocyte foot process
      effacement in STZ rats. In addition, both puerarin and losartan increased
      expression of podocyte slit diaphragm proteins such as nephrin and podocin.
      Interestingly, we found that puerarin treatment induced a more pronounced
      suppression of oxidative stress production and S-nitrosylation of proteins in the
      diabetic kidneys as compared to losartan treatment. Furthermore, we found that
      matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative
      stress and S-nitrosylation of proteins, was also suppressed more extensively by
      puerarin than losartan. In conclusion, these data provide for the first time the
      potential mechanism to support the use of puerarin in the treatment of early
      diabetic nephropathy. 

PMID- 24454920
TI  - National trends over one decade in hospitalization for acute myocardial
      infarction among Spanish adults with type 2 diabetes: cumulative incidence,
      outcomes and use of percutaneous coronary intervention.
AB  - BACKGROUND: This study aims to describe trends in the rate of acute myocardial
      infarction (AMI) and use of percutaneous coronary interventions (PCI) in patients
      with and without type 2 diabetes in Spain, 2001-2010. METHODS: We selected all
      patients with a discharge of AMI using national hospital discharge data.
      Discharges were grouped by diabetes status: type 2 diabetes and no diabetes. In
      both groups PCIs were identified. The cumulative incidence of discharges
      attributed to AMI were calculated overall and stratified by diabetes status and
      year. We calculated length of stay and in-hospital mortality (IHM). Use of PCI
      was calculated stratified by diabetes status. Multivariate analysis was adjusted
      by age, sex, year and comorbidity. RESULTS: From 2001 to 2010, 513,517 discharges
      with AMI were identified (30.3% with type 2 diabetes). The cumulative incidence
      of discharges due to AMI in diabetics patients increased (56.3 in 2001 to 71
      cases per 100,000 in 2004), then decreased to 61.9 in 2010. Diabetic patients had
      significantly higher IHM (OR, 1.14; 95%CI, 1.05-1.17). The proportion of diabetic
      patients that underwent PCI increased from 11.9% in 2001 to 41.6% in 2010.
      Adjusted incidence of discharge in patients with diabetes who underwent PCI
      increased significantly (IRR, 3.49; 95%CI, 3.30-3.69). The IHM among diabetics
      patients who underwent a PCI did not change significantly over time. CONCLUSIONS:
      AMI hospitalization rates increased initially but declining slowly. From 2001 to
      2010 the proportion of diabetic patients who undergo a PCI increased almost four
      fold. Older age and more comorbidity may explain why IHM did not improve after a
      PCI.

PMID- 24454921
TI  - Metabolic effects of acute thiamine depletion are reversed by rapamycin in breast
      and leukemia cells.
AB  - Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently
      altered in cancer and therefore present cancer-relevant targets. We have
      previously shown that the recombinant enzyme thiaminase cleaves and depletes
      intracellular thiamine, has growth inhibitory activity against leukemia and
      breast cancer cell lines, and that its growth inhibitory effects were reversed in
      leukemia cell lines by rapamycin. Now, we first show further evidence of
      thiaminase therapeutic potential by demonstrating its activity against breast and
      leukemia xenografts, and against a primary leukemia xenograft. We therefore
      further explored the metabolic effects of thiaminase in combination with
      rapamycin in leukemia and breast cell lines. Thiaminase decreased oxygen
      consumption rate and increased extracellular acidification rate, consistent with
      the inhibitory effect of acute thiamine depletion on the activity of the TDEs
      pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes; these effects
      were reversed by rapamycin. Metabolomic studies demonstrated intracellular
      thiamine depletion and the presence of the thiazole cleavage product in
      thiaminase-treated cells, providing validation of the experimental procedures.
      Accumulation of ribose and ribulose in both cell lines support the thiaminase
      mediated suppression of the TDE transketolase. Interestingly, thiaminase
      suppression of another TDE, branched chain amino ketoacid dehydrogenase (BCKDH),
      showed very different patterns in the two cell lines: in RS4 leukemia cells it
      led to an increase in BCKDH substrates, and in MCF-7 breast cancer cells it led
      to a decrease in BCKDH products. Immunoblot analyses showed corresponding
      differences in expression of BCKDH pathway enzymes, and partial protection of
      thiaminase growth inhibition by gabapentin indicated that BCKDH inhibition may be
      a mechanism of thiaminase-mediated toxicity. Surprisingly, most of thiaminase
      mediated metabolomic effects were also reversed by rapamycin. Thus, these studies
      demonstrate that acute intracellular thiamine depletion by recombinant thiaminase
      results in metabolic changes in thiamine-dependent metabolism, and demonstrate a
      previously unrecognized role of mTOR signaling in the regulation of thiamine
      dependent metabolism. 

PMID- 24454922
TI  - Rare variant association testing by adaptive combination of P-values.
AB  - With the development of next-generation sequencing technology, there is a great
      demand for powerful statistical methods to detect rare variants (minor allele
      frequencies (MAFs)<1%) associated with diseases. Testing for each variant site
      individually is known to be underpowered, and therefore many methods have been
      proposed to test for the association of a group of variants with phenotypes, by
      pooling signals of the variants in a chromosomal region. However, this pooling
      strategy inevitably leads to the inclusion of a large proportion of neutral
      variants, which may compromise the power of association tests. To address this
      issue, we extend the [Formula: see text]-MidP method (Cheung et al., 2012, Genet
      Epidemiol 36: 675-685) and propose an approach (named 'adaptive combination of P
      values for rare variant association testing', abbreviated as 'ADA') that
      adaptively combines per-site P-values with the weights based on MAFs. Before
      combining P-values, we first imposed a truncation threshold upon the per-site P
      values, to guard against the noise caused by the inclusion of neutral variants.
      This ADA method is shown to outperform popular burden tests and non-burden tests
      under many scenarios. ADA is recommended for next-generation sequencing data
      analysis where many neutral variants may be included in a functional region. 

PMID- 24454923
TI  - Sodium-coupled neutral amino acid transporter 1 (SNAT1) modulates L-citrulline
      transport and nitric oxide (NO) signaling in piglet pulmonary arterial
      endothelial cells.
AB  - RATIONALE: There is evidence that impairments in nitric oxide (NO) signaling
      contribute to chronic hypoxia-induced pulmonary hypertension. The L-arginine-NO
      precursor, L-citrulline, has been shown to ameliorate pulmonary hypertension.
      Sodium-coupled neutral amino acid transporters (SNATs) are involved in the
      transport of L-citrulline into pulmonary arterial endothelial cells (PAECs). The
      functional link between the SNATs, L-citrulline, and NO signaling has not yet
      been explored. OBJECTIVE: We tested the hypothesis that changes in SNAT1
      expression and transport function regulate NO production by modulating eNOS
      coupling in newborn piglet PAECs. METHODS AND RESULTS: A silencing RNA (siRNA)
      technique was used to assess the contribution of SNAT1 to NO production and eNOS
      coupling (eNOS dimer-to-monomer ratios) in PAECs from newborn piglets cultured
      under normoxic and hypoxic conditions in the presence and absence of L
      citrulline. SNAT1 siRNA reduced basal NO production in normoxic PAECs and
      prevented L-citrulline-induced elevations in NO production in both normoxic and
      hypoxic PAECs. SNAT1 siRNA reduced basal eNOS dimer-to-monomer ratios in normoxic
      PAECs and prevented L-citrulline-induced increases in eNOS dimer-to-monomer
      ratios in hypoxic PAECs. CONCLUSIONS: SNAT1 mediated L-citrulline transport
      modulates eNOS coupling and thus regulates NO production in hypoxic PAECs from
      newborn piglets. Strategies that increase SNAT1-mediated transport and supply of
      L-citrulline may serve as novel therapeutic approaches to enhance NO production
      in patients with pulmonary vascular disease.

PMID- 24454924
TI  - Aspergillus nidulans cell wall composition and function change in response to
      hosting several Aspergillus fumigatus UDP-galactopyranose mutase activity
      mutants.
AB  - Deletion or repression of Aspergillus nidulans ugmA (AnugmA), involved in
      galactofuranose biosynthesis, impairs growth and increases sensitivity to
      Caspofungin, a beta-1,3-glucan synthesis antagonist. The A. fumigatus UgmA
      (AfUgmA) crystal structure has been determined. From that study, AfUgmA mutants
      with altered enzyme activity were transformed into AnugmA? to assess their effect
      on growth and wall composition in A. nidulans. The complemented (AnugmA::wild
      type AfugmA) strain had wild type phenotype, indicating these genes had
      functional homology. Consistent with in vitro studies, AfUgmA residues R182 and
      R327 were important for its function in vivo, with even conservative amino (RK)
      substitutions producing AnugmA? phenotype strains. Similarly, the conserved
      AfUgmA loop III histidine (H63) was important for Galf generation: the H63N
      strain had a partially rescued phenotype compared to AnugmA?. Collectively, A.
      nidulans strains that hosted mutated AfUgmA constructs with low enzyme activity
      showed increased hyphal surface adhesion as assessed by binding fluorescent latex
      beads. Consistent with previous qPCR results, immunofluorescence and ELISA
      indicated that AnugmA? and AfugmA-mutated A. nidulans strains had increased alpha
      glucan and decreased beta-glucan in their cell walls compared to wild type and
      AfugmA-complemented strains. Like the AnugmA? strain, A. nidulans strains
      containing mutated AfugmA showed increased sensitivity to antifungal drugs,
      particularly Caspofungin. Reduced beta-glucan content was correlated with
      increased Caspofungin sensitivity. Aspergillus nidulans wall Galf, alpha-glucan,
      and beta-glucan content was correlated in A. nidulans hyphal walls, suggesting
      dynamic coordination between cell wall synthesis and cell wall integrity. 

PMID- 24454925
TI  - Downregulation of PAX6 by shRNA inhibits proliferation and cell cycle progression
      of human non-small cell lung cancer cell lines.
AB  - BACKGROUND: The transcription factor PAX6 is primarily expressed in embryos. PAX6
      is also expressed in several tumors and plays an oncogenic role. However, little
      is known about the role of PAX6 in lung cancer. METHODS: The function of PAX6 in
      lung cancer cells was evaluated by small interfering RNA-mediated depletion of
      the protein followed by analyses of cell proliferation, anchorage-independent
      growth, and cell cycle arrest. The changes of cyclin D1, pRB, ERK1/2, p38
      expression caused by PAX6 inhibition were detected using western-blotting. The
      PAX6 mRNA level in 52 pairs of tumors and corresponding matched adjacent normal
      tissues from non-small cell lung cancer patients and lung cancer cell lines was
      detected by real-time PCR. RESULTS: Suppression of PAX6 expression inhibited cell
      growth and colony formation in A549 and H1299 cells. The percentage of cells in
      G1-phase increased when PAX6 expression was inhibited. The cyclin D1 protein
      level, as well as the pRB phosphorylation level, decreased as a result of PAX6
      down-regulation. The activity of ERK1/2 and p38 was also suppressed in PAX6 knock
      down cells. The PAX6 mRNA was highly expressed in lung cancer tissue and lung
      cancer cell lines. In most patients (about 65%), the relative ratio of PAX6 mRNA
      in primary NSCLC versus adjacent tissues exceeded 100. CONCLUSIONS: Our data
      implicated that PAX6 accelerates cell cycle progression by activating MAPK signal
      pathway. PAX6 mRNA levels were significantly elevated in primary lung cancer
      tissues compared to their matched adjacent tissues.

PMID- 24454926
TI  - Combined impact of cardiorespiratory fitness and visceral adiposity on metabolic
      syndrome in overweight and obese adults in Korea.
AB  - BACKGROUND: Obesity, especially visceral obesity, is known to be an important
      correlate for cardiovascular disease and increased mortality. On the other hand,
      high cardiorespiratory fitness is suggested to be an effective contributor for
      reducing this risk. This study was conducted to determine the combined impact of
      cardiorespiratory fitness and visceral adiposity, otherwise known as fitness and
      fatness, on metabolic syndrome in overweight and obese adults. METHODS: A total
      of 232 overweight and obese individuals were grouped into four subtypes according
      to their fitness level. This was measured by recovery heart rate from a step test
      in addition to visceral adiposity defined as the visceral adipose tissue area to
      subcutaneous adipose tissue area ratio (VAT/SAT ratio). Associations of fitness
      and visceral fatness were analyzed in comparison with the prevalence of metabolic
      syndrome. RESULTS: The high visceral fat and low fitness group had the highest
      prevalence of metabolic syndrome [Odds Ratio (OR) 5.02; 95% Confidence Interval
      (CI) 1.85-13.61] compared with the reference group, which was the low visceral
      adiposity and high fitness group, after adjustments for confounding factors.
      Viscerally lean but unfit subjects were associated with a higher prevalence of
      metabolic syndrome than more viscerally obese but fit subjects (OR 3.42; 95% CI
      1.27-9.19, and OR 2.70; 95% CI 1.01-7.25, respectively). CONCLUSIONS: Our study
      shows that visceral obesity and fitness levels are cumulatively associated with a
      higher prevalence of metabolic syndrome in healthy overweight and obese adults.
      This suggests that cardiorespiratory fitness is a significant modifier in the
      relation of visceral adiposity to adverse metabolic outcomes in overweight and
      obese individuals.

PMID- 24454927
TI  - Perceptual and gaze biases during face processing: related or not?
AB  - Previous studies have demonstrated a left perceptual bias while looking at faces,
      due to the fact that observers mainly use information from the left side of a
      face (from the observer's point of view) to perform a judgment task. Such a bias
      is consistent with the right hemisphere dominance for face processing and has
      sometimes been linked to a left gaze bias, i.e. more and/or longer fixations on
      the left side of the face. Here, we recorded eye-movements, in two different
      experiments during a gender judgment task, using normal and chimeric faces which
      were presented above, below, right or left to the central fixation point or on it
      (central position). Participants performed the judgment task by remaining fixated
      on the fixation point or after executing several saccades (up to three). A left
      perceptual bias was not systematically found as it depended on the number of
      allowed saccades and face position. Moreover, the gaze bias clearly depended on
      the face position as the initial fixation was guided by face position and landed
      on the closest half-face, toward the center of gravity of the face. The analysis
      of the subsequent fixations revealed that observers move their eyes from one side
      to the other. More importantly, no apparent link between gaze and perceptual
      biases was found here. This implies that we do not look necessarily toward the
      side of the face that we use to make a gender judgment task. Despite the fact
      that these results may be limited by the absence of perceptual and gaze biases in
      some conditions, we emphasized the inter-individual differences observed in terms
      of perceptual bias, hinting at the importance of performing individual analysis
      and drawing attention to the influence of the method used to study this bias. 

PMID- 24454928
TI  - Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype
      phenotype correlation.
AB  - X-linked Retinitis Pigmentosa (XLRP) accounts for 10-20% of all RP cases, and
      represents the most severe subtype of this disease. Mutations in the Retinitis
      Pigmentosa GTPase Regulator (RPGR) gene are the most common causes of XLRP,
      accounting for over 70-75% of all XLRP cases. In this work, we analyzed all the
      exons of RPGR gene with Sanger sequencing in seven Chinese XLRP families, two of
      these with a provisional diagnosis of adRP but without male-to-male transmission.
      Three novel deletions (c.2233_34delAG; c.2236_37delGA and c.2403_04delAG) and two
      known nonsense mutations (c.851C->G and c.2260G->T) were identified in five
      families. Two novel deletions (c.2233_34delAG and c.2236_37delGA) resulted in the
      same frame shift (p.E746RfsX22), created similar phenotype in Family 3 and 4. The
      novel deletion (c.2403_04delAG; p.E802GfsX31) resulted in both XLRP and x-linked
      cone-rod dystrophy within the male patients of family 5, which suggested the
      presence of either genetic or environmental modifiers, or both, play a
      substantial role in disease expression. Genotype-phenotype correlation analysis
      suggested that (1) both patients and female carriers with mutation in Exon 8
      (Family 1) manifest more severe disease than did those with ORF15 mutations
      (Family 2&3&4); (2) mutation close to downstream of ORF15 (Family 5) demonstrate
      the early preferential loss of cone function with moderate loss of rod function. 

PMID- 24454929
TI  - A synthetic dl-nordihydroguaiaretic acid (Nordy), inhibits angiogenesis, invasion
      and proliferation of glioma stem cells within a zebrafish xenotransplantation
      model.
AB  - The zebrafish (Danio rerio) and their transparent embryos represent a promising
      model system in cancer research. Compared with other vertebrate model systems, we
      had previously shown that the zebrafish model provides many advantages over mouse
      or chicken models to study tumor invasion, angiogenesis, and tumorigenesis. In
      this study, we systematically investigated the biological features of glioma stem
      cells (GSCs) in a zebrafish model, such as tumor angiogenesis, invasion, and
      proliferation. We demonstrated that several verified anti-angiogenic agents
      inhibited angiogenesis that was induced by xenografted-GSCs. We next evaluated
      the effects of a synthetic dl-nordihydroguaiaretic acid compound (dl-NDGA or
      "Nordy"), which revealed anti-tumor activity against human GSCs in vitro by
      establishing parameters through studying its ability to suppress angiogenesis,
      tumor invasion, and proliferation. Furthermore, our results indicated that Nordy
      might inhibit GSCs invasion and proliferation through regulation of the
      arachidonate 5-lipoxygenase (Alox-5) pathway. Moreover, the combination of Nordy
      and a VEGF inhibitor exhibited an enhanced ability to suppress angiogenesis that
      was induced by GSCs. By contrast, even following treatment with 50 uM Nordy,
      there was no discernible effect on zebrafish embryonic development. Together,
      these results suggested efficacy and safety of using Nordy in vivo, and further
      demonstrated that this model should be suitable for studying GSCs and anti-GSC
      drug evaluation. 

PMID- 24454930
TI  - Antimicrobial cathelicidin peptide LL-37 inhibits the LPS/ATP-induced pyroptosis
      of macrophages by dual mechanism.
AB  - Pyroptosis is a caspase-1 dependent cell death, associated with proinflammatory
      cytokine production, and is considered to play a crucial role in sepsis.
      Pyroptosis is induced by the two distinct stimuli, microbial PAMPs (pathogen
      associated molecular patterns) and endogenous DAMPs (damage associated molecular
      patterns). Importantly, cathelicidin-related AMPs (antimicrobial peptides) have a
      role in innate immune defense. Notably, human cathelicidin LL-37 exhibits the
      protective effect on the septic animal models. Thus, in this study, to elucidate
      the mechanism for the protective action of LL-37 on sepsis, we utilized LPS
      (lipopolysaccharide) and ATP (adenosine triphosphate) as a PAMP and a DAMP,
      respectively, and examined the effect of LL-37 on the LPS/ATP-induced pyroptosis
      of macrophage-like J774 cells. The data indicated that the stimulation of J774
      cells with LPS and ATP induces the features of pyroptosis, including the
      expression of IL-1beta mRNA and protein, activation of caspase-1, inflammasome
      formation and cell death. Moreover, LL-37 inhibits the LPS/ATP-induced IL-1beta
      expression, caspase-1 activation, inflammasome formation, as well as cell death.
      Notably, LL-37 suppressed the LPS binding to target cells and ATP-induced/P2X7
      mediated caspase-1 activation. Together these observations suggest that LL-37
      potently inhibits the LPS/ATP-induced pyroptosis by both neutralizing the action
      of LPS and inhibiting the response of P2X7 to ATP. Thus, the present finding may
      provide a novel insight into the modulation of sepsis utilizing LL-37 with a dual
      action on the LPS binding and P2X7 activation. 

PMID- 24454931
TI  - Determinants of mortality and loss to follow-up among adults enrolled in HIV care
      services in Rwanda.
AB  - BACKGROUND: Antiretroviral therapy (ART) improves morbidity and mortality in
      patients with HIV, however high rates of loss to follow-up (LTF) and mortality
      have been documented in HIV care and treatment programs. METHODS: We analyzed
      routinely-collected data on HIV-infected patients >= 15 years enrolled at 41
      healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not
      attending clinic in the last 12 months for pre-ART patients and 6 months for ART
      patients. For the pre-ART period, sub-distribution hazards models were
      constructed to estimate LTF and death to account for competing risks. Kaplan
      Meier (KM) and Cox proportional hazards models were used for patients on ART.
      RESULTS: 31,033 ART-naive adults were included, 64% were female and 75% were WHO
      stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART
      competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9-11.6%) and 2.9%
      for death (95%CI 2.7-3.1%). Among pre-ART patients, male gender was associated
      with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1-1.5) and death
      (aSHR 1.7, 95%CI 1.4-2.1). Low CD4 count (CD4<100 vs. >= 350 aSHR 0.2, 95%CI 0.1
      0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2-0.6) were
      protective against pre-ART LTF. KM estimates for LTF and death in ART patients at
      2 years were 4.4% (95%CI 4.4-4.5%) and 6.3% (95%CI 6.2-6.4%). In patients on ART,
      male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2
      1.7) and death (AHR1.3, 95%CI 1.2-1.5). Mortality was higher for ART patients >=
      40 years and in those with lower CD4 count at ART initiation. CONCLUSIONS: Low
      rates of LTF and death were founds among pre-ART and ART patients in Rwanda but
      greater efforts are needed to retain patients in care prior to ART initiation,
      particularly among those who are healthy at enrollment.

PMID- 24454932
TI  - Nlrp3 prevents early renal interstitial edema and vascular permeability in
      unilateral ureteral obstruction.
AB  - Progressive renal disease is characterized by tubulo-interstitial injury with
      ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these
      pathophysiological processes through its canonical effects in cytokine
      maturation. Nlrp3 may additionally exert inflammasome-independent effects
      following tissue injury. Hence, in this study we investigated potential non
      canonical effects of Nlrp3 following progressive renal injury by subjecting WT
      and Nlrp3-deficient (-/-) mice to unilateral ureter obstruction (UUO). Our
      results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following
      UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and
      an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial
      edema was significantly elevated in Nlrp3-/- mice. This could be explained by
      increased intratubular pressure and an enhanced tubular and vascular
      permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice
      that associated with reduced mRNA expression of intercellular junction
      components. The decreased epithelial barrier function in Nlrp3-/- mice was not
      associated with increased apoptosis and/or proliferation of renal epithelial
      cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together,
      our data reveal a novel non-canonical effect of Nlrp3 in preserving renal
      integrity and protection against early tubular injury and interstitial edema
      following progressive renal injury. 

PMID- 24454933
TI  - Imaging the directed transport of single engineered RNA transcripts in real-time
      using ratiometric bimolecular beacons.
AB  - The relationship between RNA expression and cell function can often be difficult
      to decipher due to the presence of both temporal and sub-cellular processing of
      RNA. These intricacies of RNA regulation can often be overlooked when only
      acquiring global measurements of RNA expression. This has led to development of
      several tools that allow for the real-time imaging of individual engineered RNA
      transcripts in living cells. Here, we describe a new technique that utilizes an
      oligonucleotide-based probe, ratiometric bimolecular beacon (RBMB), to image RNA
      transcripts that were engineered to contain 96-tandem repeats of the RBMB target
      sequence in the 3'-untranslated region. Binding of RBMBs to the target RNA
      resulted in discrete bright fluorescent spots, representing individual
      transcripts, that could be imaged in real-time. Since RBMBs are a synthetic
      probe, the use of photostable, bright, and red-shifted fluorophores led to a high
      signal-to-background. RNA motion was readily characterized by both mean squared
      displacement and moment scaling spectrum analyses. These analyses revealed clear
      examples of directed, Brownian, and subdiffusive movements. 

PMID- 24454934
TI  - Changes in fish assemblages following the establishment of a network of no-take
      marine reserves and partially-protected areas.
AB  - Networks of no-take marine reserves and partially-protected areas (with limited
      fishing) are being increasingly promoted as a means of conserving biodiversity.
      We examined changes in fish assemblages across a network of marine reserves and
      two different types of partially-protected areas within a marine park over the
      first 5 years of its establishment. We used Baited Remote Underwater Video (BRUV)
      to quantify fish communities on rocky reefs at 20-40 m depth between 2008-2011.
      Each year, we sampled 12 sites in 6 no-take marine reserves and 12 sites in two
      types of partially-protected areas with contrasting levels of protection (n = 4
      BRUV stations per site). Fish abundances were 38% greater across the network of
      marine reserves compared to the partially-protected areas, although not all
      individual reserves performed equally. Compliance actions were positively
      associated with marine reserve responses, while reserve size had no apparent
      relationship with reserve performance after 5 years. The richness and abundance
      of fishes did not consistently differ between the two types of partially
      protected areas. There was, therefore, no evidence that the more regulated
      partially-protected areas had additional conservation benefits for reef fish
      assemblages. Overall, our results demonstrate conservation benefits to fish
      assemblages from a newly established network of temperate marine reserves. They
      also show that ecological monitoring can contribute to adaptive management of
      newly established marine reserve networks, but the extent of this contribution is
      limited by the rate of change in marine communities in response to protection.

PMID- 24454935
TI  - Isolation and biochemical characterization of a glucose dehydrogenase from a hay
      infusion metagenome.
AB  - Glucose hydrolyzing enzymes are essential to determine blood glucose level. A
      high-throughput screening approach was established to identify NAD(P)-dependent
      glucose dehydrogenases for the application in test stripes and the respective
      blood glucose meters. In the current report a glucose hydrolyzing enzyme, derived
      from a metagenomic library by expressing recombinant DNA fragments isolated from
      hay infusion, was characterized. The recombinant clone showing activity on
      glucose as substrate exhibited an open reading frame of 987 bp encoding for a
      peptide of 328 amino acids. The isolated enzyme showed typical sequence motifs of
      short-chain-dehydrogenases using NAD(P) as a co-factor and had a sequence
      similarity between 33 and 35% to characterized glucose dehydrogenases from
      different Bacillus species. The identified glucose dehydrogenase gene was
      expressed in E. coli, purified and subsequently characterized. The enzyme,
      belonging to the superfamily of short-chain dehydrogenases, shows a broad
      substrate range with a high affinity to glucose, xylose and glucose-6-phosphate.
      Due to its ability to be strongly associated with its cofactor NAD(P), the enzyme
      is able to directly transfer electrons from glucose oxidation to external
      electron acceptors by regenerating the cofactor while being still associated to
      the protein. 

PMID- 24454936
TI  - Response to phosphorus limitation varies among lake populations of the freshwater
      snail Potamopyrgus antipodarum.
AB  - Local adaptation--typically recognized as higher values of fitness-related traits
      for native vs. non-native individuals when measured in the native environment--is
      common in natural populations because of pervasive spatial variation in the
      intensity and type of natural selection. Although local adaptation has been
      primarily studied in the context of biotic interactions, widespread variation in
      abiotic characteristics of environments suggests that local adaptation in
      response to abiotic factors should also be common. Potamopyrgus antipodarum, a
      freshwater New Zealand snail that is an important model system for invasion
      biology and the maintenance of sexual reproduction, exhibits local adaptation to
      parasites and rate of water flow. As an initial step to determining whether P.
      antipodarum are also locally adapted to phosphorus availability, we examined
      whether populations differ in their responses to phosphorus limitation. We found
      that field-collected juvenile P. antipodarum grew at a lower rate and reached an
      important size threshold more slowly when fed a relatively low vs. a relatively
      high-phosphorus diet. We also detected significant across-population variation in
      individual growth rate. A marginally significant population-by-dietary phosphorus
      interaction along with a two-fold difference across populations in the extent of
      suppression of growth by low phosphorus suggests that populations of P.
      antipodarum may differ in their response to phosphorus limitation. Local
      adaptation may explain this variation, with the implication that snails from
      lakes with relatively low phosphorus availability should be less severely
      affected by phosphorus limitation than snails from lakes with higher phosphorus
      availability.

PMID- 24454937
TI  - Lipid metabolism, oxidative stress and cell death are regulated by PKC delta in a
      dietary model of nonalcoholic steatohepatitis.
AB  - Steatosis, oxidative stress, and apoptosis underlie the development of
      nonalcoholic steatohepatitis (NASH). Protein kinase C delta (PKCdelta) has been
      implicated in fatty liver disease and is activated in the methionine and choline
      deficient (MCD) diet model of NASH, yet its pathophysiological importance towards
      steatohepatitis progression is uncertain. We therefore addressed the role of
      PKCdelta in the development of steatosis, inflammation, oxidative stress,
      apoptosis, and fibrosis in an animal model of NASH. We fed PKCdelta(-/-) mice and
      wildtype littermates a control or MCD diet. PKCdelta(-/-) primary hepatocytes
      were used to evaluate the direct effects of fatty acids on hepatocyte lipid
      metabolism gene expression. A reduction in hepatic steatosis and triglyceride
      levels were observed between wildtype and PKCdelta(-/-) mice fed the MCD diet.
      The hepatic expression of key regulators of beta-oxidation and plasma
      triglyceride metabolism was significantly reduced in PKCdelta(-/-) mice and
      changes in serum triglyceride were blocked in PKCdelta(-/-) mice. MCD diet
      induced hepatic oxidative stress and hepatocyte apoptosis were reduced in
      PKCdelta(-/-) mice. MCD diet-induced NADPH oxidase activity and p47(phox)
      membrane translocation were blunted and blocked, respectively, in PKCdelta(-/-)
      mice. Expression of pro-apoptotic genes and caspase 3 and 9 cleavage in the liver
      of MCD diet fed PKCdelta(-/-) mice were blunted and blocked, respectively.
      Surprisingly, no differences in MCD diet-induced fibrosis or pro-fibrotic gene
      expression were observed in 8 week MCD diet fed PKCdelta(-/-) mice. Our results
      suggest that PKCdelta plays a role in key pathological features of fatty liver
      disease but not ultimately in fibrosis in the MCD diet model of NASH. 

PMID- 24454938
TI  - Independently outgrowing neurons and geometry-based synapse formation produce
      networks with realistic synaptic connectivity.
AB  - Neuronal signal integration and information processing in cortical networks
      critically depend on the organization of synaptic connectivity. During
      development, neurons can form synaptic connections when their axonal and
      dendritic arborizations come within close proximity of each other. Although many
      signaling cues are thought to be involved in guiding neuronal extensions, the
      extent to which accidental appositions between axons and dendrites can already
      account for synaptic connectivity remains unclear. To investigate this, we
      generated a local network of cortical L2/3 neurons that grew out independently of
      each other and that were not guided by any extracellular cues. Synapses were
      formed when axonal and dendritic branches came by chance within a threshold
      distance of each other. Despite the absence of guidance cues, we found that the
      emerging synaptic connectivity showed a good agreement with available
      experimental data on spatial locations of synapses on dendrites and axons, number
      of synapses by which neurons are connected, connection probability between
      neurons, distance between connected neurons, and pattern of synaptic
      connectivity. The connectivity pattern had a small-world topology but was not
      scale free. Together, our results suggest that baseline synaptic connectivity in
      local cortical circuits may largely result from accidentally overlapping axonal
      and dendritic branches of independently outgrowing neurons. 

PMID- 24454939
TI  - Pyrotag sequencing of the gut microbiota of the cockroach Shelfordella lateralis
      reveals a highly dynamic core but only limited effects of diet on community
      structure.
AB  - Although blattid cockroaches and termites share a common ancestor, their diets
      are distinctly different. While termites consume a highly specialized diet of
      lignocellulose, cockroaches are omnivorous and opportunistic feeders. The role of
      the termite gut microbiota has been studied intensively, but little is known
      about the cockroach gut microbiota and its function in digestion and nutrition,
      particularly the adaptation to different diets. Our analyses of the bacterial gut
      microbiota of the blattid cockroach Shelfordella lateralis combining terminal
      restriction fragment length polymorphism of their 16S rRNA genes with
      physiological parameters (microbial metabolites, hydrogen and methane emission)
      indicated substantial variation between individuals but failed to identify any
      diet-related response. Subsequent deep-sequencing of the 16S rRNA genes of the
      colonic gut microbiota of S. lateralis fed either a high- or a low-fiber diet
      confirmed the absence of bacterial taxa that responded to diet. Instead, we found
      a small number of abundant phylotypes that were consistently present in all
      samples and made up half of the community in both diet groups. They varied
      strongly in abundance between individual samples at the genus but not at the
      family level. The remaining phylotypes were inconsistently present among
      replicate batches. Our findings suggest that S. lateralis harbors a highly
      dynamic core gut microbiota that is maintained even after fundamental dietary
      shifts, and that any dietary effects on the gut community are likely to be masked
      by strong individual variations. 

PMID- 24454940
TI  - Pooled screening for synergistic interactions subject to blocking and noise.
AB  - The complex molecular networks in the cell can give rise to surprising
      interactions: gene deletions that are synthetically lethal, gene overexpressions
      that promote stemness or differentiation, synergistic drug interactions that
      heighten potency. Yet, the number of actual interactions is dwarfed by the number
      of potential interactions, and discovering them remains a major problem. Pooled
      screening, in which multiple factors are simultaneously tested for possible
      interactions, has the potential to increase the efficiency of searching for
      interactions among a large set of factors. However, pooling also carries with it
      the risk of masking genuine interactions due to antagonistic influence from other
      factors in the pool. Here, we explore several theoretical models of pooled
      screening, allowing for synergy and antagonism between factors, noisy
      measurements, and other forms of uncertainty. We investigate randomized
      sequential designs, deriving formulae for the expected number of tests that need
      to be performed to discover a synergistic interaction, and the optimal size of
      pools to test. We find that even in the presence of significant antagonistic
      interactions and testing noise, randomized pooled designs can significantly
      outperform exhaustive testing of all possible combinations. We also find that
      testing noise does not affect optimal pool size, and that mitigating noise by a
      selective approach to retesting outperforms naive replication of all tests.
      Finally, we show that a Bayesian approach can be used to handle uncertainty in
      problem parameters, such as the extent of synergistic and antagonistic
      interactions, resulting in schedules for adapting pool size during the course of
      testing.

PMID- 24454941
TI  - The role of the Staphylococcal VraTSR regulatory system on vancomycin resistance
      and vanA operon expression in vancomycin-resistant Staphylococcus aureus.
AB  - Vancomycin is often the preferred treatment for invasive methicillin-resistant
      Staphylococcus aureus (MRSA) infection. With the increase in incidence of MRSA
      infections, the use of vancomycin has increased and, as feared, isolates of
      vancomycin-resistant Staphylococcus aureus (VRSA) have emerged. VRSA isolates
      have acquired the entercoccal vanA operon contained on transposon (Tn) 1546
      residing on a conjugal plasmid. VraTSR is a vancomycin and beta-lactam-inducible
      three-component regulatory system encoded on the S. aureus chromosome that
      modulates the cell-wall stress response to cell-wall acting antibiotics. Mutation
      in vraTSR has shown to increase susceptibility to beta-lactams and vancomycin in
      clinical VISA strains and in recombinant strain COLVA-200 which expresses a
      plasmid borne vanA operon. To date, the role of VraTSR in vanA operon expression
      in VRSA has not been demonstrated. In this study, the vraTSR operon was deleted
      from the first clinical VRSA strain (VRS1) by transduction with phage harvested
      from a USA300 vraTSR operon deletion strain. The absence of the vraTSR operon and
      presence of the vanA operon were confirmed in the transductant (VRS1Deltavra) by
      PCR. Broth MIC determinations, demonstrated that the vancomycin MIC of
      VRS1Deltavra (64 ug/ml) decreased by 16-fold compared with VRS1 (1024 ug/ml). The
      effect of the vraTSR operon deletion on expression of the van gene cluster (vanA,
      vanX and vanR) was examined by quantitative RT-PCR using relative quantification.
      A 2-5-fold decreased expression of the vanA operon genes occured in strain
      VRS1Deltavra at stationary growth phase compared with the parent strain, VRS1.
      Both vancomycin resistance and vancomycin-induced expression of vanA and vanR
      were restored by complementation with a plasmid harboring the vraTSR operon.
      These findings demonstrate that expression in S. aureus of the horizontally
      acquired enterococcal vanA gene cluster is enhanced by the staphylococcal three
      component cell wall stress regulatory system VraTSR, that is present in all S.
      aureus strains. 

PMID- 24454942
TI  - Anti-allergic role of cholinergic neuronal pathway via alpha7 nicotinic ACh
      receptors on mucosal mast cells in a murine food allergy model.
AB  - The prevalence of food allergy (FA) has increased in developed countries over the
      past few decades. However, no effective drug therapies are currently available.
      Therefore, we investigated cholinergic anti-inflammatory pathway as a regulatory
      system to ameliorate disrupted mucosal immune homeostasis in the gut based on the
      pathophysiological elucidation of mucosal mast cells (MMCs) in a murine FA model.
      BALB/c mice sensitized with ovalbumin received repeated oral ovalbumin for the
      development of FA. FA mice developed severe allergic diarrhea and exhibited
      enhanced type 2 helper T (Th2) cell immune responses in both systemic immunity
      and mucosal immunity, along with MMCs hyperplasia in the colon. MMCs were
      localized primarily in the strategic position of the mucosal epithelium.
      Furthermore, the allergic symptoms did not develop in p85alpha disrupted
      phosphoinositide-3 kinase-deficient mice that lacked mast cells in the gut. Vagal
      stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor
      (nAChR) agonists (nicotine and alpha7 nAChR agonist GTS-21) alleviated the
      allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia,
      enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA
      mice colon. MMCs, which are negatively regulated by alpha7 nAChRs, were often
      located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the
      FA mice colon. The present results reveal that the cholinergic neuroimmune
      interaction via alpha7 nAChRs on MMCs is largely involved in maintaining
      intestinal immune homeostasis and can be a target for a new therapy against
      mucosal immune diseases with homeostatic disturbances such as FA. 

PMID- 24454943
TI  - High rate of per oral mecillinam treatment failure in community-acquired urinary
      tract infections caused by ESBL-producing Escherichia coli.
AB  - A population-based study was performed to investigate the efficacy of mecillinam
      treatment of community-acquired urinary tract infections (CA-UTI) caused by
      extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. The study was
      conducted in South-Eastern Norway. Data from patients with CA-UTI caused by ESBL
      producing and non-producing (random controls) E. coli were collected through
      interviews, questionnaires, medical records and the Norwegian Prescription
      Database. Treatment failure was defined as a new antibiotic prescription
      appropriate for UTI prescribed within two weeks after the initial antimicrobial
      therapy. Multivariable logistic regression analysis was performed to identify
      treatment agents and patient- or bacterial traits associated with treatment
      failure. A total of 343 patients (mean age 59) were included, of which 158 (46%)
      were treated with mecillinam. Eighty-one patients (24%, mean age 54) had
      infections caused by ESBL producing E. coli, and 41 of these patients (51%)
      received mecillinam as the primary treatment. Mecillinam treatment failure was
      observed in 18 (44%) of patients infected by ESBL-producing strains and in 16
      (14%) of patients with a CA-UTI caused by ESBL non-producing strains.
      Multivariable analysis showed that ESBL status (odds ratio (OR) 3.2, 95%
      confidence interval (CI) 1.3-7.8, p = 0.009) and increased MIC of mecillinam (OR
      2.0 for each doubling value of MIC, CI 1.4-3.0, p<0.001) were independently
      associated with mecillinam treatment failure. This study showed a high rate of
      mecillinam treatment failure in CA-UTIs caused by ESBL producing E. coli. The
      high failure rate could not be explained by the increased MIC of mecillinam
      alone. Further studies addressing the use of mecillinam against ESBL-producing E.
      coli, with emphasis on optimal dosing and combination therapy with beta-lactamase
      inhibitors, are warranted.

PMID- 24454944
TI  - Penam sulfones and beta-lactamase inhibition: SA2-13 and the importance of the C2
      side chain length and composition.
AB  - beta-Lactamases are the major reason beta-lactam resistance is seen in Gram
      negative bacteria. To combat this resistance mechanism, beta-lactamase inhibitors
      are currently being developed. Presently, there are only three that are in
      clinical use (clavulanate, sulbactam and tazobactam). In order to address this
      important medical need, we explored a new inhibition strategy that takes
      advantage of a long-lived inhibitory trans-enamine intermediate. SA2-13 was
      previously synthesized and shown to have a lower k(react) than tazobactam. We
      investigated here the importance of the carboxyl linker length and composition by
      synthesizing three analogs of SA2-13 (PSR-4-157, PSR-4-155, and PSR-3-226). All
      SA2-13 analogs yielded higher turnover numbers and k(react) compared to SA2-13.
      We next demonstrated using protein crystallography that increasing the linker
      length by one carbon allowed for better capture of a trans-enamine intermediate;
      in contrast, this trans-enamine intermediate did not occur when the C2 linker
      length was decreased by one carbon. If the linker was altered by both shortening
      it and changing the carboxyl moiety into a neutral amide moiety, the stable trans
      enamine intermediate in wt SHV-1 did not form; this intermediate could only be
      observed when a deacylation deficient E166A variant was studied. We subsequently
      studied SA2-13 against a relatively recently discovered inhibitor-resistant (IR)
      variant of SHV-1, SHV K234R. Despite the alteration in the mechanism of
      resistance due to the K->R change in this variant, SA2-13 was effective at
      inhibiting this IR enzyme and formed a trans-enamine inhibitory intermediate
      similar to the intermediate seen in the wt SHV-1 structure. Taken together, our
      data reveals that the C2 side chain linker length and composition profoundly
      affect the formation of the trans-enamine intermediate of penam sulfones. We also
      show that the design of SA2-13 derivatives offers promise against IR SHV beta
      lactamases that possess the K234R substitution.

PMID- 24454945
TI  - Habitat characteristics predicting distribution and abundance patterns of
      scallops in D'Entrecasteaux Channel, Tasmania.
AB  - Habitat characteristics greatly influence the patterns of distribution and
      abundance in scallops, providing structure for the settlement of spat and
      influencing predation risk and rates of survival. Establishing scallop-habitat
      relationships is relevant to understanding the ecological processes that regulate
      scallop populations and to managing critical habitats. This information is
      particularly relevant for the D'Entrecasteaux Channel, south-eastern Tasmania
      (147.335 W, 43.220 S), a region that has supported significant but highly
      variable scallop production over many years, including protracted periods of
      stock collapse. Three species of scallops are present in the region; the
      commercial scallop Pecten fumatus, the queen scallop Equichlamys bifrons, and the
      doughboy scallop Mimachlamys asperrima. We used dive surveys and Generalized
      Additive Modelling to examine the relationship between the distribution and
      abundance patterns of each species and associated habitat characteristics. The
      aggregated distribution of each species could be predicted as a function of
      sediment type and species-specific habitat structural components. While P.
      fumatus was strongly associated with finer sediments and E. bifrons with coarse
      grain sediments, M. asperrima had a less selective association, possibly related
      to its ability to attach on a wide range of substrates. Other habitat
      characteristics explaining P. fumatus abundance were depth, Asterias amurensis
      abundance, shell and macroalgae cover. Equichlamys bifrons was strongly
      associated with macroalgae and seagrass cover, whereas M. asperrima abundance was
      greatly explained by sponge cover. The models define a set of relationships from
      which plausible hypotheses can be developed. We propose that these relationships
      are mediated by predation pressure as well as the specific behavioural
      characteristics of each species. The findings also highlight the specific habitat
      characteristics that are relevant for spatial management and habitat restoration
      plans. 

PMID- 24454947
TI  - Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular
      trafficking in brain microvascular endothelial cells.
AB  - In this study, a detailed characterization of Monocarboxylic Acid Transporter-1
      (Mct1) in cytoplasmic vesicles of cultured rat brain microvascular endothelial
      cells shows them to be a diverse population of endosomes intrinsic to the
      regulation of the transporter by a brief 25 to 30 minute exposure to the membrane
      permeant cAMP analog, 8Br-cAMP. The vesicles are heterogeneous in size, mobility,
      internal pH, and co-localize with discreet markers of particular types of
      endosomes including early endosomes, clathrin coated vesicles, caveolar vesicles,
      trans-golgi, and lysosomes. The vesicular localization of Mct1 was not dependent
      on its N or C termini, however, the size and pH of Mct1 vesicles was increased by
      deletion of either terminus demonstrating a role for the termini in vesicular
      trafficking of Mct1. Using a novel BCECF-AM based assay developed in this study,
      8Br-cAMP was shown to decrease the pH of Mct1 vesicles after 25 minutes. This
      result and method were confirmed in experiments with a ratiometric pH-sensitive
      EGFP-mCherry dual tagged Mct1 construct. Overall, the results indicate that cAMP
      signaling reduces the functionality of Mct1 in cerebrovascular endothelial cells
      by facilitating its entry into a highly dynamic vesicular trafficking pathway
      that appears to lead to the transporter's trafficking to autophagosomes and
      lysosomes. 

PMID- 24454946
TI  - Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T
      cells.
AB  - The glycosylphosphatidylinositol (GPI)-anchored molecule CD59 has been implicated
      in the modulation of T cell responses, but the underlying molecular mechanism of
      CD59 influencing T cell signaling remained unclear. Here we analyzed Jurkat T
      cells stimulated via anti-CD3epsilon- or anti-CD59-coated surfaces, using time
      resolved single-cell Ca(2+) imaging as a read-out for stimulation. This analysis
      revealed a heterogeneous Ca(2+) response of the cell population in a stimulus
      dependent manner. Further analysis of T cell receptor (TCR)/CD3 deficient or
      overexpressing cells showed that CD59-mediated signaling is strongly dependent on
      TCR/CD3 surface expression. In protein co-patterning and fluorescence recovery
      after photobleaching experiments no direct physical interaction was observed
      between CD59 and CD3 at the plasma membrane upon anti-CD59 stimulation. However,
      siRNA-mediated protein knock-downs of downstream signaling molecules revealed
      that the Src family kinase Lck and the adaptor molecule linker of activated T
      cells (LAT) are essential for both signaling pathways. Furthermore, flow
      cytometry measurements showed that knock-down of Lck accelerates CD3 re
      expression at the cell surface after anti-CD59 stimulation similar to what has
      been observed upon direct TCR/CD3 stimulation. Finally, physically linking Lck to
      CD3zeta completely abolished CD59-triggered Ca(2+) signaling, while signaling was
      still functional upon direct TCR/CD3 stimulation. Altogether, we demonstrate that
      Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T
      cells, and propose that CD59 may act via Lck to modulate T cell responses. 

PMID- 24454948
TI  - Characterization of angiotensin-converting enzyme 2 ectodomain shedding from
      mouse proximal tubular cells.
AB  - Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney proximal
      tubule, where it cleaves angiotensin (Ang) II to Ang-(1-7). Urinary ACE2 levels
      increase in diabetes, suggesting that ACE2 may be shed from tubular cells. The
      aim of this study was to determine if ACE2 is shed from proximal tubular cells,
      to characterize ACE2 fragments, and to study pathways for shedding. Studies
      involved primary cultures of mouse proximal tubular cells, with ACE2 activity
      measured using a synthetic substrate, and analysis of ACE2 fragments by
      immunoblots and mass spectrometry. The culture media from mouse proximal tubular
      cells demonstrated a time-dependent increase in ACE2 activity, suggesting
      constitutive ACE2 shedding. ACE2 was detected in media as two bands at ~ 90 kDa
      and ~ 70 kDa on immunoblots. By contrast, full-length ACE2 appeared at ~ 100 kDa
      in cell lysates or mouse kidney cortex. Mass spectrometry of the two
      deglycosylated fragments identified peptides matching mouse ACE2 at positions 18
      706 and 18-577, respectively. The C-terminus of the 18-706 peptide fragment
      contained a non-tryptic site, suggesting that Met(706) is a candidate ACE2
      cleavage site. Incubation of cells in high D-glucose (25 mM) (and to a lesser
      extent Ang II) for 48-72 h increased ACE2 activity in the media (p<0.001), an
      effect blocked by inhibition of a disintegrin and metalloproteinase (ADAM)17.
      High D-glucose increased ADAM17 activity in cell lysates (p<0.05). These data
      indicate that two glycosylated ACE2 fragments are constitutively shed from mouse
      proximal tubular cells. ACE2 shedding is stimulated by high D-glucose, at least
      partly via an ADAM17-mediated pathway. The results suggest that proximal tubular
      shedding of ACE2 may increase in diabetes, which could enhance degradation of Ang
      II in the tubular lumen, and increase levels of Ang-(1-7).

PMID- 24454949
TI  - Fasting for 24 hours heightens reward from food and food-related cues.
AB  - INTRODUCTION: We examined the impact of a 24 hour complete fast (vs. fed state)
      on two measures of food reward: 1) 'wanting', as measured by response to food
      images and by the relative-reinforcing value of food (RRV), and 2) 'liking', as
      measured by response to food images and the hedonic evaluation of foods consumed.
      METHODS: Utilizing a randomized crossover design, 15 subjects (9 male; 6 female)
      aged 28.6+/-4.5 yrs with body mass index 25.3+/-1.4 kg/m(2) were randomized and
      counterbalanced to normal feeding (FED) and 24-hour fast (FASTED) conditions.
      Trait characteristics were measured with the Three Factor Eating Questionnaire.
      Two computer tasks measured food reward: 1) RRV progressive ratio task, 2)
      explicit 'liking' and 'wanting' (Leeds Food Preference Questionnaire, LFPQ). Also
      measured were ad libitum energy intake (EI; buffet) and food 'liking' (visual
      analogue scale) of personalized stimuli. RESULTS: There were no significant
      anthropometric changes between conditions. Appetite scores, hedonic ratings of
      'liking', and ad libitum EI all significantly increased under the FASTED
      condition (p<0.05). Under the FASTED condition there were significant increases
      in the RRV of snack foods; similarly, explicit 'wanting' and 'liking'
      significantly increased for all food categories. 'Liking' of sweet foods remained
      high across-meals under FASTED, but savory foods decreased in hedonic saliency.
      CONCLUSION: Relative to a fed state, we observed an increase in hedonic ratings
      of food, the rewarding value of food, and food intake after a 24 hr fast.
      Alliesthesia to food and food cues is suggested by heightened hedonic ratings
      under the FASTED condition relative to FED.

PMID- 24454950
TI  - Correlates of chlamydia and gonorrhea infection among female sex workers: the
      untold story of Jiangsu, China.
AB  - OBJECTIVES: To estimate the prevalence of sexually transmitted infections (STIs)
      among female sex workers (FSWs) in the Jiangsu Province, China and measure the
      association of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
      infections with their potential correlates. DESIGN: A cross-sectional study on a
      representative sample of FSWs in Yangzhou and Changzhou cities of Jiangsu was
      conducted. METHODS: 185 sex-work venues in Yangzhou and 174 in Changzhou were
      selected by stratified random sampling. 2972 FSWs (1108 in Yangzhou and 1864 in
      Changzhou), aged 15 years or more, who agreed to participate and provided blood
      sample for HIV and syphilis testing were interviewed in these venues. Cervical
      specimens from 849 randomly chosen participants were then tested for CT and NG.
      RESULTS: Proportions of young, school-educated, currently married FSWs who were
      living alone, migrated from other provinces and engaged in unprotected vaginal
      intercourse in past 3 months (UVI) were relatively high. Prevalence of HIV,
      syphilis, CT and NG were 0.20%, 4.88%, 14.61% and 5.42% respectively. Younger
      age, living alone or with persons other than partners/family members, engaging in
      UVI and having other STIs seemed to be associated with higher risk of CT or NG
      infection. Being divorced/widowed and working in middle/low-level venues were
      identified as additional risk factors for NG. CONCLUSIONS: Based on a
      representative sample, this initial effort to identify the correlates of CT/NG
      infections among FSWs of Jiangsu revealed that focused interventions targeting
      high-risk FSWs are urgently required for controlling STI epidemics in Yangzhou
      and Changzhou where substantial number of STI cases were identified.

PMID- 24454951
TI  - Extrapunitive and intropunitive individuals activate different parts of the
      prefrontal cortex under an ego-blocking frustration.
AB  - Different people make different responses when they face a frustrating situation:
      some punish others (extrapunitive), while others punish themselves
      (intropunitive). Few studies have investigated the neural structures that
      differentiate extrapunitive and intropunitive individuals. The present fMRI study
      explored these neural structures using two different frustrating situations: an
      ego-blocking situation which blocks a desire or goal, and a superego-blocking
      situation which blocks self-esteem. In the ego-blocking condition, the
      extrapunitive group (n = 9) showed greater activation in the bilateral
      ventrolateral prefrontal cortex, indicating that these individuals prefer
      emotional processing. On the other hand, the intropunitive group (n = 9) showed
      greater activation in the left dorsolateral prefrontal cortex, possibly
      reflecting an effortful control for anger reduction. Such patterns were not
      observed in the superego-blocking condition. These results indicate that the
      prefrontal cortex is the source of individual differences in aggression direction
      in the ego-blocking situation.

PMID- 24454953
TI  - Anchoring revisited: the role of the comparative question.
AB  - When people estimate a numeric value after judging whether it is larger or
      smaller than a high or low anchor value (comparative question), estimates are
      biased in the direction of the anchor. One explanation for this anchoring effect
      is that people selectively access knowledge consistent with the anchor value as
      part of a positive test strategy. Two studies (total N = 184) supported the
      alternative explanation that people access knowledge consistent with their own
      answer to the comparative question. Specifically, anchoring effects emerged when
      the answer to the comparative question was unexpected (lower than the low anchor
      or higher than the high anchor). For expected answers (lower than the high anchor
      or higher than the low anchor), however, anchoring effects were attenuated or
      reversed. The anchor value itself was almost never reported as an absolute
      estimate. 

PMID- 24454952
TI  - A two-stage association study suggests BRAP as a susceptibility gene for
      schizophrenia.
AB  - Schizophrenia (SZ) is a neurodevelopmental disorder in which altered immune
      function typically plays an important role in mediating the effect of
      environmental insults and regulation of inflammation. The breast cancer
      suppressor protein associated protein (BRAP) is suggested to exert vital effects
      in neurodevelopment by modulating the mitogen-activated protein kinase cascade
      and inflammation signaling. To explore the possible role of BRAP in SZ, we
      conducted a two-stage study to examine the association of BRAP polymorphisms with
      SZ in the Han Chinese population. In stage one, we screened SNPs in BRAP from our
      GWAS data, which detected three associated SNPs, with rs3782886 being the most
      significant one (P  =  2.31E-6, OR  =  0.67). In stage two, we validated these
      three SNPs in an independently collected population including 1957 patients and
      1509 controls, supporting the association of rs3782886 with SZ (P  =  1.43E-6, OR
      =  0.73). Furthermore, cis-eQTL analysis indicates that rs3782886 genotypes are
      associated with mRNA levels of aldehyde dehydrogenase 2 family (ALDH2) (P  = 
      0.0039) and myosin regulatory light chain 2 (MYL2) (P < 1.0E-4). Our data suggest
      that the BRAP gene may confer vulnerability for SZ in Han Chinese population,
      adding further evidence for the involvement of developmental and/or
      neuroinflammatory cascades in the illness. 

PMID- 24454954
TI  - Protective effect of metalloporphyrins against cisplatin-induced kidney injury in
      mice.
AB  - Oxidative and nitrative stress is a well-known phenomenon in cisplatin-induced
      nephrotoxicity. The purpose of this work is to study the role of two
      metalloporphyrins (FeTMPyP and MnTBAP), water soluble complexes, in cisplatin
      induced renal damage and their ability to scavenge peroxynitrite. In cisplatin
      induced nephropathy study in mice, renal nitrative stress was evident by the
      increase in protein nitration. Cisplatin-induced nephrotoxicity was also evident
      by the histological damage from the loss of the proximal tubular brush border,
      blebbing of apical membranes, tubular epithelial cell detachment from the
      basement membrane, or intra-luminal aggregation of cells and proteins and by the
      increase in blood urea nitrogen and serum creatinine. Cisplatin-induced apoptosis
      and cell death as shown by Caspase 3 assessments, TUNEL staining and DNA
      fragmentation Cisplatin-induced nitrative stress, apoptosis and nephrotoxicity
      were attenuated by both metalloporphyrins. Heme oxygenase (HO-1) also plays a
      critical role in metalloporphyrin-mediated protection of cisplatin-induced
      nephrotoxicity. It is evident that nitrative stress plays a critical role in
      cisplatin-induced nephrotoxicity in mice. Our data suggest that peroxynitrite is
      involved, at least in part, in cisplatin-induced nephrotoxicity and protein
      nitration and cisplatin-induced nephrotoxicity can be prevented with the use of
      metalloporphyrins. 

PMID- 24454955
TI  - The RNA chaperone Hfq impacts growth, metabolism and production of virulence
      factors in Yersinia enterocolitica.
AB  - To adapt to changes in environmental conditions, bacteria regulate their gene
      expression at the transcriptional but also at the post-transcriptional level,
      e.g. by small RNAs (sRNAs) which modulate mRNA stability and translation. The
      conserved RNA chaperone Hfq mediates the interaction of many sRNAs with their
      target mRNAs, thereby playing a global role in fine-tuning protein production. In
      this study, we investigated the significance of Hfq for the enteropathogen
      Yersina enterocolitica serotype O:8. Hfq facilitated optimal growth in complex
      and minimal media. Our comparative protein analysis of parental and hfq-negative
      strains suggested that Hfq promotes lipid metabolism and transport, cell redox
      homeostasis, mRNA translation and ATP synthesis, and negatively affects carbon
      and nitrogen metabolism, transport of siderophore and peptides and tRNA
      synthesis. Accordingly, biochemical tests indicated that Hfq represses ornithine
      decarboxylase activity, indole production and utilization of glucose, mannitol,
      inositol and 1,2-propanediol. Moreover, Hfq repressed production of the
      siderophore yersiniabactin and its outer membrane receptor FyuA. In contrast, hfq
      mutants exhibited reduced urease production. Finally, strains lacking hfq were
      more susceptible to acidic pH and oxidative stress. Unlike previous reports in
      other Gram-negative bacteria, Hfq was dispensable for type III secretion encoded
      by the virulence plasmid. Using a chromosomally encoded FLAG-tagged Hfq, we
      observed increased production of Hfq-FLAG in late exponential and stationary
      phases. Overall, Hfq has a profound effect on metabolism, resistance to stress
      and modulates the production of two virulence factors in Y. enterocolitica,
      namely urease and yersiniabactin. 

PMID- 24454956
TI  - Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle
      differentiation and chemotaxis.
AB  - In the recent decade, embryonic stem cells (ESC) have emerged as an attractive
      cell source of smooth muscle cells (SMC) for vascular tissue engineering owing to
      their unlimited self-renewal and differentiation capacities. Despite their
      promise in therapy, their efficacy is still hampered by the lack of definitive
      SMC differentiation mechanisms and difficulties in successful trafficking of the
      ESC towards a site of injury or target tissue. Heat shock protein 47 (HSP47) is a
      47-kDa molecular chaperone that is required for the maturation of various types
      of collagen and has been shown to be a critical modulator of different
      pathological and physiological processes. To date, the role of HSP47 on ESC to
      SMC differentiation or ESC chemotaxis is not known and may represent a potential
      molecular approach by which ESC can be manipulated to increase their efficacy in
      clinic. We provide evidence that HSP47 is highly expressed during ESC
      differentiation into the SMC lineage and that HSP47 reduction results in an
      attenuation of the differentiation. Our experiments using a HSP47 plasmid
      transfection system show that gene over-expression is sufficient to induce ESC
      SMC differentiation, even in the absence of exogenous stimuli. Furthermore, HSP47
      over-expression in ESC also increases their chemotaxis and migratory responses
      towards a panel of chemokines, likely via the upregulation of chemokine
      receptors. Our findings provide direct evidence of induced ESC migration and
      differentiation into SMC via the over-expression of HSP47, thus identifying a
      novel approach of molecular manipulation that can potentially be exploited to
      improve stem cell therapy for vascular repair and regeneration. 

PMID- 24454957
TI  - Production of pigs expressing a transgene under the control of a tetracycline
      inducible system.
AB  - Pigs are anatomically and physiologically closer to humans than other laboratory
      animals. Transgenic (TG) pigs are widely used as models of human diseases. The
      aim of this study was to produce pigs expressing a tetracycline (Tet)-inducible
      transgene. The Tet-on system was first tested in infected donor cells. Porcine
      fetal fibroblasts were infected with a universal doxycycline-inducible vector
      containing the target gene enhanced green fluorescent protein (eGFP). At 1 day
      after treatment with 1 ug/ml doxycycline, the fluorescence intensity of these
      cells was increased. Somatic cell nuclear transfer (SCNT) was then performed
      using these donor cells. The Tet-on system was then tested in the generated
      porcine SCNT-TG embryos. Of 4,951 porcine SCNT-TG embryos generated, 850 were
      cultured in the presence of 1 ug/ml doxycycline in vitro. All of these embryos
      expressed eGFP and 15 embryos developed to blastocyst stage. The remaining 4,101
      embryos were transferred to thirty three surrogate pigs from which thirty eight
      cloned TG piglets were obtained. PCR analysis showed that the transgene was
      inserted into the genome of each of these piglets. Two TG fibroblast cell lines
      were established from these TG piglets, and these cells were used as donor cells
      for re-cloning. The re-cloned SCNT embryos expressed the eGFP transgene under the
      control of doxycycline. These data show that the expression of transgenes in
      cloned TG pigs can be regulated by the Tet-on/off systems. 

PMID- 24454958
TI  - Fragmentation of care threatens patient safety in peripheral vascular catheter
      management in acute care--a qualitative study.
AB  - BACKGROUND: The use of peripheral vascular catheters (PVCs) is an extremely
      common and necessary clinical intervention, but inappropriate PVC care poses a
      major patient safety risk in terms of infection. Quality improvement initiatives
      have been proposed to reduce the likelihood of adverse events, but a lack of
      understanding about factors that influence behaviours of healthcare professionals
      limits the efficacy of such interventions. We undertook qualitative interviews
      with clinical staff from a large group of hospitals in order to understand
      influences on PVC care behaviors and subsequent patient safety. METHODS: Ten
      doctors, ten clinical pharmacists, 18 nurses and one midwife at a National Health
      Service hospital group in London (United Kingdom) were interviewed between
      December 2010 and July 2011 using qualitative methods. Responses were analysed
      using a thematic framework. RESULTS: FOUR KEY THEMES EMERGED: 1) Fragmentation of
      management and care, demonstrated with a lack of general overview and
      insufficient knowledge about expected standards of care or responsibility of
      different professionals; 2) feelings of resentment and frustration as a result of
      tensions in the workplace, due to the ambiguity about professional
      responsibilities; 3) disregard for existing hospital policy due to perceptions of
      flaws in the evidence used to support it; and 4) low-risk perception for the
      impact of PVC use on patient safety. CONCLUSION: Fragmentation of practice
      resulted in ill-defined responsibilities and interdisciplinary resentment, which
      coupled with a generally low perception of risk of catheter use, appeared to
      result in lack of maintaining policy PVC standards which could reduced patient
      safety. Resolution of these issues through clearly defining handover practice,
      teaching interdisciplinary duties and increasing awareness of PVC risks could
      result in preventing thousands of BSIs and other PVC-related infections annually.

PMID- 24454959
TI  - Risky drinking patterns are being continued into pregnancy: a prospective cohort
      study.
AB  - BACKGROUND: Risky patterns of alcohol use prior to pregnancy increase the risk of
      alcohol-exposed pregnancies and subsequent adverse outcomes. It is important to
      understand how consumption changes once women become pregnant. OBJECTIVE: The aim
      of this study was to describe the characteristics of women that partake in risky
      drinking patterns before pregnancy and to examine how these patterns change once
      they become pregnant. METHODS: A sample of 1577 women from the 1973-78 cohort of
      the Australian Longitudinal Study on Women's Health were included if they first
      reported being pregnant in 2000, 2003, 2006, 2009 and reported risky drinking
      patterns prior to that pregnancy. Multinomial logistic regression was used to
      determine which risky drinking patterns were most likely to continue into
      pregnancy. RESULTS: When reporting risky drinking patterns prior to pregnancy
      only 6% of women reported weekly drinking only, whereas 46% reported binge
      drinking only and 48% reported both. Women in both binge categories were more
      likely to have experienced financial stress, not been partnered, smoked, used
      drugs, been nulliparous, experienced a violent relationship, and were less
      educated. Most women (46%) continued these risky drinking patterns into
      pregnancy, with 40% reducing these behaviors, and 14% completely ceasing alcohol
      consumption. Once pregnant, women who binged only prior to pregnancy were more
      likely to continue (55%) rather than reduce drinking (29%). Of the combined
      drinking group 61% continued to binge and 47% continued weekly drinking. Compared
      with the combined drinking group, binge only drinkers prior to pregnancy were
      less likely to reduce rather than continue their drinking once pregnant (OR =
      0.37, 95% CI  =  0.29, 0.47). CONCLUSIONS: Over a third of women continued risky
      drinking into pregnancy, especially binge drinking, suggesting a need to address
      alcohol consumption prior to pregnancy.

PMID- 24454960
TI  - Using environmental DNA to census marine fishes in a large mesocosm.
AB  - The ocean is a soup of its resident species' genetic material, cast off in the
      forms of metabolic waste, shed skin cells, or damaged tissue. Sampling this
      environmental DNA (eDNA) is a potentially powerful means of assessing whole
      biological communities, a significant advance over the manual methods of
      environmental sampling that have historically dominated marine ecology and
      related fields. Here, we estimate the vertebrate fauna in a 4.5-million-liter
      mesocosm aquarium tank at the Monterey Bay Aquarium of known species composition
      by sequencing the eDNA from its constituent seawater. We find that it is
      generally possible to detect mitochondrial DNA of bony fishes sufficient to
      identify organisms to taxonomic family- or genus-level using a 106 bp fragment of
      the 12S ribosomal gene. Within bony fishes, we observe a low false-negative
      detection rate, although we did not detect the cartilaginous fishes or sea
      turtles present with this fragment. We find that the rank abundance of recovered
      eDNA sequences correlates with the abundance of corresponding species' biomass in
      the mesocosm, but the data in hand do not allow us to develop a quantitative
      relationship between biomass and eDNA abundance. Finally, we find a low false
      positive rate for detection of exogenous eDNA, and we were able to diagnose non
      native species' tissue in the food used to maintain the mesocosm, underscoring
      the sensitivity of eDNA as a technique for community-level ecological surveys. We
      conclude that eDNA has substantial potential to become a core tool for
      environmental monitoring, but that a variety of challenges remain before reliable
      quantitative assessments of ecological communities in the field become possible. 

PMID- 24454961
TI  - RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor
      cells.
AB  - BACKGROUND: Telomeric 3' overhangs can fold into a four-stranded DNA structure
      termed G-quadruplex (G4), a formation which inhibits telomerase. As telomerase
      activation is crucial for telomere maintenance in most cancer cells, several
      classes of G4 ligands have been designed to directly disrupt telomeric structure.
      METHODS: We exposed brain tumor cells to the G4 ligand 3,11-difluoro-6,8,13
      trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) and investigated
      proliferation, cell cycle dynamics, telomere length, telomerase activity and
      activated c-Myc levels. RESULTS: Although all cell lines tested were sensitive to
      RHPS4, PFSK-1 central nervous system primitive neuroectodermal cells, DAOY
      medulloblastoma cells and U87 glioblastoma cells exhibited up to 30-fold
      increased sensitivity compared to KNS42 glioblastoma, C6 glioma and Res196
      ependymoma cells. An increased proportion of S-phase cells were observed in
      medulloblastoma and high grade glioma cells whilst CNS PNET cells showed an
      increased proportion of G1-phase cells. RHPS4-induced phenotypes were concomitant
      with telomerase inhibition, manifested in a telomere length-independent manner
      and not associated with activated c-Myc levels. However, anti-proliferative
      effects were also observed in normal neural/endothelial cells in vitro and ex
      vivo. CONCLUSION: This study warrants in vivo validation of RHPS4 and alternative
      G4 ligands as potential anti-cancer agents for brain tumors but highlights the
      consideration of dose-limiting tissue toxicities.

PMID- 24454962
TI  - Genome-wide analysis of DNA methylation in five tissues of Zhikong scallop,
      Chlamys farreri.
AB  - DNA methylation plays a vital role in tissue development and differentiation in
      eukaryotes. Epigenetic studies have been seldom conducted in the extremely
      diverse and evolutionarily highly successful bilaterian lineage Mollusca. In the
      present study, we conducted the genome-wide profiling of DNA methylation for five
      tissues of a bivalve mollusc, Chlamys farreri using the methylation-sensitive
      amplification polymorphism (MSAP) technique. The methylation levels were quite
      similar among tissues, ranging from 20.9% to 21.7%. CG methylation was the
      dominant type (14.9%-16.5%) in the C. farreri genome, but CHG methylation also
      accounted for a substantial fraction of total methylation (5.1%-6.3%). Relatively
      high methylation diversity was observed within tissues. Methylation
      differentiation between tissues was evaluated and 460 tissue-specific epiloci
      were identified. Kidney differs from the other tissues in DNA methylation
      profiles. Our study presents the first look at the tissue-specific DNA
      methylation patterns in a bivalve mollusc and represents an initial step towards
      understanding of epigenetic regulatory mechanism underlying tissue development
      and differentiation in bivalves. 

PMID- 24454963
TI  - Sequence comparison for non-enhanced MRA of the lower extremity arteries at 7
      Tesla.
AB  - In this study three sequences for non-contrast-enhanced MRA of the lower
      extremity arteries at 7T were compared. Cardiac triggering was used with the aim
      to reduce signal variations in the arteries. Two fast single-shot 2D sequences, a
      modified Ultrafast Spoiled Gradient Echo (UGRE) sequence and a variant of the
      Quiescent-Interval Single-Shot (QISS) sequence were triggered via phonocardiogram
      and compared in volunteer examinations to a non-triggered 2D gradient echo (GRE)
      sequence. For image acquisition, a 16-channel transmit/receive coil and a
      manually positionable AngioSURF table were used. To tackle B1 inhomogeneities at
      7T, Time-Interleaved Acquisition of Modes (TIAMO) was integrated in GRE and UGRE.
      To compare the three sequences quantitatively, a vessel-to-background ratio (VBR)
      was measured in all volunteers and stations. In conclusion, cardiac triggering
      was able to suppress flow artifacts satisfactorily. The modified UGRE showed only
      moderate image artifacts. Averaged over all volunteers and stations, GRE reached
      a VBR of 4.18+/-0.05, UGRE 5.20+/-0.06, and QISS 2.72+/-0.03. Using cardiac
      triggering and TIAMO imaging technique was essential to perform non-enhanced MRA
      of the lower extremities vessels at 7T. The modified UGRE performed best, as
      observed artifacts were only moderate and the highest average VBR was reached. 

PMID- 24454964
TI  - An efficient large-scale retroviral transduction method involving preloading the
      vector into a RetroNectin-coated bag with low-temperature shaking.
AB  - In retroviral vector-mediated gene transfer, transduction efficiency can be
      hampered by inhibitory molecules derived from the culture fluid of virus producer
      cell lines. To remove these inhibitory molecules to enable better gene
      transduction, we had previously developed a transduction method using a
      fibronectin fragment-coated vessel (i.e., the RetroNectin-bound virus
      transduction method). In the present study, we developed a method that combined
      RetroNectin-bound virus transduction with low-temperature shaking and applied
      this method in manufacturing autologous retroviral-engineered T cells for
      adoptive transfer gene therapy in a large-scale closed system. Retroviral vector
      was preloaded into a RetroNectin-coated bag and incubated at 4 degrees C for 16 h
      on a reciprocating shaker at 50 rounds per minute. After the supernatant was
      removed, activated T cells were added to the bag. The bag transduction method has
      the advantage of increasing transduction efficiency, as simply flipping over the
      bag during gene transduction facilitates more efficient utilization of the
      retroviral vector adsorbed on the top and bottom surfaces of the bag. Finally, we
      performed validation runs of endoribonuclease MazF-modified CD4(+) T cell
      manufacturing for HIV-1 gene therapy and T cell receptor-modified T cell
      manufacturing for MAGE-A4 antigen-expressing cancer gene therapy and achieved
      over 200-fold (>= 10(10)) and 100-fold (>= 5 * 10(9)) expansion, respectively. In
      conclusion, we demonstrated that the large-scale closed transduction system is
      highly efficient for retroviral vector-based T cell manufacturing for adoptive
      transfer gene therapy, and this technology is expected to be amenable to
      automation and improve current clinical gene therapy protocols.

PMID- 24454965
TI  - A co-culture model of the developing small intestine offers new insight in the
      early immunomodulation of enterocytes and macrophages by Lactobacillus spp.
      through STAT1 and NF-kB p65 translocation.
AB  - The early establishment of a complete microbiome has been shown to play an
      integral part in the development and maintenance of an intact intestine and its
      immune system, although much remains unknown about the specific mechanisms of
      immune modulation in newborns. In our study we show in a co-culture model of the
      undeveloped small intestine that members of Lactobacillus spp. influence STAT1
      and NF-kB p65 nuclear translocation in both intestinal epithelial cells as well
      as underlying macrophages. Moreover, by using imaging flow cytometry we were able
      to monitor each individual cell and create a framework of the percentage of cells
      in which translocation occurred in challenged versus control cell populations. We
      also observed a significant difference in baseline translocation in intestinal
      cells when cultured alone versus those in a co-culture model, underpinning the
      importance of 3D models over monolayer set-ups in epithelial in vitro research.
      In conclusion, our work offers new insights into the potential routes by which
      the commensal microbiome primes the early immune system to fight pathogens, and
      shows how strain-specific these mechanisms really are. 

PMID- 24454966
TI  - Drug targets for cell cycle dysregulators in leukemogenesis: in silico docking
      studies.
AB  - Alterations in cell cycle regulating proteins are a key characteristic in
      neoplastic proliferation of lymphoblast cells in patients with Acute
      Lymphoblastic Leukemia (ALL). The aim of our study was to investigate whether the
      routinely administered ALL chemotherapeutic agents would be able to bind and
      inhibit the key deregulated cell cycle proteins such as--Cyclins E1, D1, D3, A1
      and Cyclin Dependent Kinases (CDK) 2 and 6. We used Schrodinger Glide docking
      protocol to dock the chemotherapeutic drugs such as Doxorubicin and Daunorubicin
      and others which are not very common including Clofarabine, Nelarabine and
      Flavopiridol, to the crystal structures of these proteins. We observed that the
      drugs were able to bind and interact with cyclins E1 and A1 and CDKs 2 and 6
      while their docking to cyclins D1 and D3 were not successful. This binding proved
      favorable to interact with the G1/S cell cycle phase proteins that were examined
      in this study and may lead to the interruption of the growth of leukemic cells.
      Our observations therefore suggest that these drugs could be explored for use as
      inhibitors for these cell cycle proteins. Further, we have also highlighted
      residues which could be important in the designing of pharmacophores against
      these cell cycle proteins. This is the first report in understanding the
      mechanism of action of the drugs targeting these cell cycle proteins in leukemia
      through the visualization of drug-target binding and molecular docking using
      computational methods.

PMID- 24454967
TI  - Unscreened water-diversion pipes pose an entrainment risk to the threatened green
      sturgeon, Acipenser medirostris.
AB  - Over 3,300 unscreened agricultural water diversion pipes line the levees and
      riverbanks of the Sacramento River (California) watershed, where the threatened
      Southern Distinct Population Segment of green sturgeon, Acipenser medirostris,
      spawn. The number of sturgeon drawn into (entrained) and killed by these pipes is
      greatly unknown. We examined avoidance behaviors and entrainment susceptibility
      of juvenile green sturgeon (35+/-0.6 cm mean fork length) to entrainment in a
      large (>500-kl) outdoor flume with a 0.46-m-diameter water-diversion pipe. Fish
      entrainment was generally high (range: 26-61%), likely due to a lack of avoidance
      behavior prior to entering inescapable inflow conditions. We estimated that up to
      52% of green sturgeon could be entrained after passing within 1.5 m of an active
      water-diversion pipe three times. These data suggest that green sturgeon are
      vulnerable to unscreened water-diversion pipes, and that additional research is
      needed to determine the potential impacts of entrainment mortality on declining
      sturgeon populations. Data under various hydraulic conditions also suggest that
      entrainment-related mortality could be decreased by extracting water at lower
      diversion rates over longer periods of time, balancing agricultural needs with
      green sturgeon conservation. 

PMID- 24454968
TI  - Reconsidering the sedentary behaviour paradigm.
AB  - AIMS: Recent literature has posed sedentary behaviour as an independent entity to
      physical inactivity. This study investigated whether associations between
      sedentary behaviour and cardio-metabolic biomarkers remain when analyses are
      adjusted for total physical activity. METHODS: Cross-sectional analyses were
      undertaken on 4,618 adults from the 2003/04 and 2005/06 U.S. National Health and
      Nutrition Examination Survey. Minutes of sedentary behaviour and moderate-to
      vigorous physical activity (MVPA), and total physical activity (total daily
      accelerometer counts minus counts accrued during sedentary minutes) were
      determined from accelerometry. Associations between sedentary behaviour and
      cardio-metabolic biomarkers were examined using linear regression. RESULTS:
      Results showed that sedentary behaviour was detrimentally associated with 8/11
      cardio-metabolic biomarkers when adjusted for MVPA. However, when adjusted for
      total physical activity, the associations effectively disappeared, except for C
      reactive protein, which showed a very small, favourable association (beta = 
      0.06) and triglycerides, which showed a very small, detrimental association (beta
      = 0.04). Standardised betas suggested that total physical activity was
      consistently, favourably associated with cardio-metabolic biomarkers (9/11
      biomarkers, standardized beta = 0.08-0.30) while sedentary behaviour was
      detrimentally associated with just 1 biomarker (standardized beta = 0.12).
      CONCLUSION: There is virtually no association between sedentary behaviour and
      cardio-metabolic biomarkers once analyses are adjusted for total physical
      activity. This suggests that sedentary behaviour may not have health effects
      independent of physical activity.

PMID- 24454969
TI  - Fear inhibition in high trait anxiety.
AB  - Trait anxiety is recognized as an individual risk factor for the development of
      anxiety disorders but the neurobiological mechanisms remain unknown. Here we test
      whether trait anxiety is associated with impaired fear inhibition utilizing the
      AX+/BX- conditional discrimination procedure that allows for the independent
      evaluation of startle fear potentiation and inhibition of fear. Sixty
      undergraduate students participated in the study--High Trait Anxious: n = 28 and
      Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of
      conditioned inhibition for startle responses requires contingency awareness.
      However, contrary to the fear inhibition hypothesis, our data suggest that high
      trait anxious individuals show a normal fear inhibition of conditioned startle
      responding. Only at the cognitive level the high trait anxious individuals showed
      evidence for impaired inhibitory learning of the threat cue. Together with other
      findings where impaired fear inhibition was only observed in those PTSD patients
      who were either high on hyperarousal symptoms or with current anxiety symptoms,
      we question whether impaired fear inhibition is a biomarker for the development
      of anxiety disorders.

PMID- 24454970
TI  - Safety and efficacy of single dose versus multiple doses of AmBisome for
      treatment of visceral leishmaniasis in eastern Africa: a randomised trial.
AB  - BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome
      could be suitable for eastern African patients with symptomatic visceral
      leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY: A
      multi-centre, open-label, non-inferiority, randomized controlled trial with an
      adaptive design, was conducted to compare the efficacy and safety of a single
      dose and multiple doses of AmBisome for the treatment of VL in eastern Africa.
      The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic
      patients with parasitologically-confirmed, non-severe VL, received a single dose
      of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5,
      14, and 21. If interim analyses, evaluated 30 days after the start of treatment
      following 40 or 80 patients, showed the single dose gave significantly poorer
      parasite clearance than multiple doses at the 5% significance level, the single
      dose was increased by 2.5 mg/kg. In a sub-set of patients, parasite clearance was
      measured by quantitative reverse transcriptase (qRT) PCR. PRINCIPAL FINDINGS: The
      trial was terminated after the third interim analysis because of low efficacy of
      both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73
      93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with
      multiple doses (n = 63), and single doses of 7.5 (n = 21) or 10 mg/kg (n = 40),
      respectively. qRT-PCR suggested superior parasite clearance with multiple doses
      as early as day 3. Safety data accorded with the drug label. CONCLUSIONS: The
      tested AmBisome regimens would not be suitable for VL treatment across eastern
      Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION:
      www.clinicaltrials.govNCT00832208.

PMID- 24454971
TI  - Regional differences of leptospirosis in Sri Lanka: observations from a flood
      associated outbreak in 2011.
AB  - Leptospirosis is known to be an important cause of weather disaster-related
      infectious disease epidemics. In 2011, an outbreak of leptospirosis occurred in
      the relatively dry district of Anuradhapura, Sri Lanka where diagnosis was
      resisted by local practitioners because leptospirosis was not known in the area
      and the clinical presentation was considered atypical. To identify the causative
      Leptospira associated with this outbreak, we carried out a cross-sectional study.
      Consecutive clinically suspected cases in this district were studied during a two
      and-a-half-month period. Of 96 clinically suspected cases, 32 (33.3%) were
      confirmed by qPCR, of which the etiological cause in 26 cases was identified
      using 16S rDNA sequencing to the species level. Median bacterial load was 4.1 *
      10(2)/mL (inter-quartile range 3.1-6.1 * 10(2)/mL). In contrast to a 2008 Sri
      Lankan leptospirosis outbreak in the districts of Kegalle, Kandy, and Matale, in
      which a predominance of Leptospira interrogans serovars Lai and Geyaweera was
      found, most cases in the 2011 outbreak were caused by Leptospira kirschneri.
      Seven (21.9%) confirmed cases had acute renal failure; five (15.6%) had
      myocarditis; severe thrombocytopenia (<20,000/uL) was seen in five (15.6%) cases.
      This outbreak of leptospirosis in the relatively dry zone of Sri Lanka due
      primarily to L. kirschneri was characterized by markedly different clinical
      presentations and low leptospiremia. These observations and data demonstrate the
      public health relevance of molecular diagnostics in such settings, possibly
      related to the microgeographic variations of different Leptospira species, but of
      particular value to public health intervention in what appears to have been a
      regionally neglected tropical disease.

PMID- 24454972
TI  - Increase in TGF-beta secreting CD4+CD25+ FOXP3+ T regulatory cells in anergic
      lepromatous leprosy patients.
AB  - BACKGROUND: Lepromatous leprosy caused by Mycobacterium leprae is associated with
      antigen specific T cell unresponsiveness/anergy whose underlying mechanisms are
      not fully defined. We investigated the role of CD25(+)FOXP3(+) regulatory T cells
      in both skin lesions and M.leprae stimulated PBMC cultures of 28 each of freshly
      diagnosed patients with borderline tuberculoid (BT) and lepromatous leprosy (LL)
      as well as 7 healthy household contacts of leprosy patients and 4 normal skin
      samples. METHODOLOGY/PRINCIPLE FINDINGS: Quantitative reverse transcribed PCR
      (qPCR), immuno-histochemistry/flowcytometry and ELISA were used respectively for
      gene expression, phenotype characterization and cytokine levels in PBMC culture
      supernatants. Both skin lesions as well as in vitro antigen stimulated PBMC
      showed increased percentage/mean fluorescence intensity of cells and higher gene
      expression for FOXP3(+), TGF-beta in lepromatous (p<0.01) as compared to
      tuberculoid leprosy patients. CD4(+)CD25(+)FOXP3(+) T cells (Tregs) were
      increased in unstimulated basal cultures (p<0.0003) and showed further increase
      in in vitro antigen but not mitogen (phytohemaglutinin) stimulated PBMC (iTreg)
      in lepromatous as compared to tuberculoid leprosy patients (p<0.002). iTregs of
      lepromatous patients showed intracellular TGF-beta which was further confirmed by
      increase in TGF-beta in culture supernatants (p<0.003). Furthermore, TGF-beta in
      iTreg cells was associated with phosphorylation of STAT5A. TGF-beta was seen in
      CD25(+) cells of the CD4(+) but not that of CD8(+) T cell lineage in leprosy
      patients. iTregs did not show intracellular IFN-gamma or IL-17 in lepromatous
      leprosy patients. CONCLUSIONS/SIGNIFICANCE: Our results indicate that FOXP3(+)
      iTregs with TGF-beta may down regulate T cell responses leading to the antigen
      specific anergy associated with lepromatous leprosy.

PMID- 24454973
TI  - Clinical associations of Human T-Lymphotropic Virus type 1 infection in an
      indigenous Australian population.
AB  - INTRODUCTION: In resource-poor areas, infectious diseases may be important causes
      of morbidity among individuals infected with the Human T-Lymphotropic Virus type
      1 (HTLV-1). We report the clinical associations of HTLV-1 infection among
      socially disadvantaged Indigenous adults in central Australia. METHODOLOGY AND
      PRINCIPAL FINDINGS: HTLV-1 serological results for Indigenous adults admitted
      1(st) January 2000 to 31(st) December 2010 were obtained from the Alice Springs
      Hospital pathology database. Infections, comorbid conditions and HTLV-1 related
      diseases were identified using ICD-10 AM discharge morbidity codes. Relevant
      pathology and imaging results were reviewed. Disease associations, admission
      rates and risk factors for death were compared according to HTLV-1 serostatus.
      HTLV-1 western blots were positive for 531 (33.3%) of 1595 Indigenous adults
      tested. Clinical associations of HTLV-1 infection included bronchiectasis
      (adjusted Risk Ratio, 1.35; 95% CI, 1.14-1.60), blood stream infections (BSI)
      with enteric organisms (aRR, 1.36; 95% CI, 1.05-1.77) and admission with
      strongyloidiasis (aRR 1.38; 95% CI, 1.16-1.64). After adjusting for covariates,
      HTLV-1 infection remained associated with increased numbers of BSI episodes
      (adjusted negative binomial regression, coefficient, 0.21; 95% CI, 0.02-0.41) and
      increased admission numbers with strongyloidiasis (coefficient, 0.563; 95% CI,
      0.17-0.95) and respiratory conditions including asthma (coefficient, 0.99; 95%
      CI, 0.27-1.7), lower respiratory tract infections (coefficient, 0.19; 95% CI,
      0.04-0.34) and bronchiectasis (coefficient, 0.60; 95% CI, 0.02-1.18). Two
      patients were admitted with adult T-cell Leukemia/Lymphoma, four with probable
      HTLV-1 associated myelopathy and another with infective dermatitis. Independent
      predictors of mortality included BSI with enteric organisms (aRR 1.78; 95% CI,
      1.15-2.74) and bronchiectasis (aRR 2.07; 95% CI, 1.45-2.98). CONCLUSION: HTLV-1
      infection contributes to morbidity among socially disadvantaged Indigenous adults
      in central Australia. This is largely due to an increased risk of other
      infections and respiratory disease. The spectrum of HTLV-1 related diseases may
      vary according to the social circumstances of the affected population.

PMID- 24454974
TI  - Aptamer based, non-PCR, non-serological detection of Chagas disease biomarkers in
      Trypanosoma cruzi infected mice.
AB  - Chagas disease affects about 5 million people across the world. The etiological
      agent, the intracellular parasite Trypanosoma cruzi (T. cruzi), can be diagnosed
      using microscopy, serology or PCR based assays. However, each of these methods
      has their limitations regarding sensitivity and specificity, and thus to
      complement these existing diagnostic methods, alternate assays need to be
      developed. It is well documented that several parasite proteins called T. cruzi
      Excreted Secreted Antigens (TESA), are released into the blood of an infected
      host. These circulating parasite antigens could thus be used as highly specific
      biomarkers of T. cruzi infection. In this study, we have demonstrated that, using
      a SELEx based approach, parasite specific ligands called aptamers, can be used to
      detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer
      (ELA) assay, similar to ELISA, was developed using biotinylated aptamers to
      demonstrate that these RNA ligands could interact with parasite targets. Aptamer
      L44 (Apt-L44) showed significant and specific binding to TESA as well as T. cruzi
      trypomastigote extract and not to host proteins or proteins of Leishmania
      donovani, a related trypanosomatid parasite. Our result also demonstrated that
      the target of Apt-L44 is conserved in three different strains of T. cruzi. In
      mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of
      binding compared to non-infected mice suggesting that it could detect a biomarker
      of T. cruzi infection. Additionally, Apt-L44 could detect these circulating
      biomarkers in both the acute phase, from 7 to 28 days post infection, and in the
      chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44
      could thus be used in a qualitative ELA assay to detect biomarkers of Chagas
      disease. 

PMID- 24454975
TI  - Gastrointestinal autonomic nerve tumor of the stomach.
AB  - PATIENT: Female, 32 FINAL DIAGNOSIS: Gastrintestinal Autonomic Nerve Tumor (GANT)
      Symptoms: anemia * anorexia * fatigue * fever * hearburn * nausea * weight loss
      MEDICATION: - Clinical Procedure: - Specialty: Gastroenterology and Hepatology.
      OBJECTIVE: Rare disease. BACKGROUND: Gastrointestinal autonomic nerve tumors
      (GANT) are extremely rare tumors that are related to gastrointestinal autonomic
      nervous plexuses. They are distinguished from stromal tumors by their unique
      ultrastructural features. Hence, their diagnosis is usually made on electron
      microscopy and immunohistochemical analyses. Although they are apparently slow
      growing tumors, they run an aggressive clinical course and often associated with
      poor prognosis which eventually leads to death. CASE REPORT: We report on a case
      of gastric GANT in a young female who was treated surgically by total
      gastrectomy. The disease, however ran an aggressive course with the development
      of distant (nodal, liver, lung, adrenal and musculo-skeletal) metastases two
      months after the radical resection. CONCLUSIONS: We believe this could be the
      first reported case of adrenal and musculo-skeletal metastases from gastric GANT
      soon after the radical gastric resection.

PMID- 24454976
TI  - Hepatomegaly and fever at the time of neutrophil recovery revealing L
      asparaginase toxicity in the treatment of acute lymphoblastic leukemia.
AB  - PATIENT: Male, 52 FINAL DIAGNOSIS: L-asparaginase associated steatohepatitis and
      pulmonary Pneumocystis Symptoms: Cholestasis * hepatomegaly MEDICATION:
      Corticosteroids * atovaquone * antioxidant therapy Clinical Procedure: Liver
      biopsy Specialty: Hematology * Infectious Disease * Hepatology. OBJECTIVE:
      Challenging differential diagnosis. BACKGROUND: L-asparaginase (L-aspa) is an
      important component of chemotherapy in acute lymphoblastic leukemia (ALL). Main
      adverse effects of L-aspa include allergic reactions, pancreatitis, thrombosis,
      and liver disturbances. L-aspa-associated steatohepatitis may be a life
      threatening disorder but has very rarely been reported in the literature. CASE
      REPORT: ALL was diagnosed in a 52-year-old man with a history of cardiovascular
      disease and obesity. Chemotherapy combining daunorubicin, vincristine,
      cyclophosphamide, and L-aspa was initiated. At the time of neutrophil recovery,
      the patient developed hepatomegaly in the context of fever and cough. On day 25,
      after 6 injections of L-aspa, liver function tests showed elevated alkaline
      phosphatase and transaminases levels. Although pulmonary Pneumocystis was
      concomitantly diagnosed, biological hepatic disturbances were attributed to L
      aspa-associated toxicity. A liver biopsy revealed severe diffuse micro- and
      macrovesicular steatosis affecting more than 50% of hepatocytes. Other causes of
      liver dysfunction were eliminated. L-aspa and other hepatotoxic treatments were
      stopped, and treatment with antioxidant therapy, atovaquone, and corticosteroids
      was initiated. The clinical outcome was rapidly favorable. CONCLUSIONS: This case
      illustrates the necessity of carefully monitoring liver function test results in
      patients receiving L-aspa. In case of major increase of hepatic enzymes, a
      hepatic biopsy should rapidly be performed to exclude differential diagnosis in
      patients with prolonged neutropenia. L-aspa should be stopped and further
      administration definitively avoided. In the present case, the early
      administration of systemic corticosteroids as treatment of the concomitant
      Pneumocystis with hypoxemia could have participated to the favorable clinical
      evolution.

PMID- 24454977
TI  - Malrotation-associated cholecystoduodenal fistula.
AB  - PATIENT: Female, 16 FINAL DIAGNOSIS: Malrotation and cholecystoduodenal fistula
      Symptoms: Abdominal pain * anorexia * fever * nausea * vomiting MEDICATION: -
      Clinical Procedure: - Specialty: Gastroenterology and Hepatology. OBJECTIVE:
      Anatomical anomaly/variation. BACKGROUND: Cholecystoduodenal fistula (CDF) is the
      most common cholecystenteric fistula. It is a late complication of gallbladder
      disease with calculus and is mainly encountered in the elderly and females. CASE
      REPORT: We report the case of a teenage patient with cholecystoduodenal fistula
      and malrotation. Direct plain abdominal x-ray demonstrated air in the biliary
      system. Computed tomography revealed CDF-associated with an anomaly of intestinal
      malrotation. She had gallstones (with a few stones in the gallbladder) and
      cholecystitis. CDF is caused by malrotation, and cholecystitis has not been
      reported before. In this regard our patient is the first and youngest reported
      case. CONCLUSIONS: We suggest that CDF is probably a consequence of malrotation.
      The patient's clinical features and operative management are presented and
      discussed with current literature.

PMID- 24454978
TI  - The risk of heart failure and cardiometabolic complications in obesity may be
      masked by an apparent healthy status of normal blood glucose.
AB  - Although many obese individuals are normoglycemic and asymptomatic of
      cardiometabolic complications, this apparent healthy state may be a misnomer.
      Since heart failure is a major cause of mortality in obesity, we investigated the
      effects of heme-oxygenase (HO) on heart failure and cardiometabolic complications
      in obese normoglycemic Zucker-fatty rats (ZFs). Treatment with the HO-inducer,
      hemin, reduced markers of heart failure, such as osteopontin and osteoprotegerin,
      abated left-ventricular (LV) hypertrophy/fibrosis, extracellular
      matrix/profibrotic proteins including collagen IV, fibronectin, TGF-beta1, and
      reduced cardiac lesions. Furthermore, hemin suppressed inflammation by abating
      macrophage chemoattractant protein-1, macrophage-inflammatory protein-1 alpha,
      TNF-alpha, IL-6, and IL-1beta but enhanced adiponectin, atrial-natriuretic
      peptide (ANP), HO activity, insulin sensitivity, and glucose metabolism.
      Correspondingly, hemin improved several hemodynamic/echocardiographic parameters
      including LV-diastolic wall thickness, LV-systolic wall thickness, mean-arterial
      pressure, arterial-systolic pressure, arterial-diastolic pressure, LV-developed
      pressure, +dP/dt, and cardiac output. Contrarily, the HO-inhibitor, stannous
      mesoporphyrin nullified the hemin effect, exacerbating inflammatory/oxidative
      insults and aggravated insulin resistance (HOMA-index). We conclude that
      perturbations in insulin signaling and cardiac function may be forerunners to
      overt hyperglycemia and heart failure in obesity. Importantly, hemin improves
      cardiac function by suppressing markers of heart failure, LV hypertrophy, cardiac
      lesions, extracellular matrix/profibrotic proteins, and inflammatory/oxidative
      mediators, while concomitantly enhancing the HO-adiponectin-ANP axis. 

PMID- 24454979
TI  - Carbon monoxide protects against hepatic ischemia/reperfusion injury via ROS
      dependent Akt signaling and inhibition of glycogen synthase kinase 3beta.
AB  - Carbon monoxide (CO) may exert important roles in physiological and
      pathophysiological states through the regulation of cellular signaling pathways.
      CO can protect organ tissues from ischemia/reperfusion (I/R) injury by modulating
      intracellular redox status and by inhibiting inflammatory, apoptotic, and
      proliferative responses. However, the cellular mechanisms underlying the
      protective effects of CO in organ I/R injury remain incompletely understood. In
      this study, a murine model of hepatic warm I/R injury was employed to assess the
      role of glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase
      (PI3K)-dependent signaling pathways in the protective effects of CO against
      inflammation and injury. Inhibition of GSK3 through the PI3K/Akt pathway played a
      crucial role in CO-mediated protection. CO treatment increased the
      phosphorylation of Akt and GSK3-beta (GSK3beta) in the liver after I/R injury.
      Furthermore, administration of LY294002, an inhibitor of PI3K, compromised the
      protective effect of CO and decreased the level of phospho-GSK3beta after I/R
      injury. These results suggest that CO protects against liver damage by
      maintaining GSK3beta phosphorylation, which may be mediated by the PI3K/Akt
      signaling pathway. Our study provides additional support for the therapeutic
      potential of CO in organ injury and identifies GSK3beta as a therapeutic target
      for CO in the amelioration of hepatic injury.

PMID- 24454981
TI  - Nucleic acid oxidation in human health and disease.

PMID- 24454980
TI  - PDGF suppresses oxidative stress induced Ca2+ overload and calpain activation in
      neurons.
AB  - Oxidative stress is crucially involved in the pathogenesis of neurological
      diseases such as stroke and degenerative diseases. We previously demonstrated
      that platelet-derived growth factors (PDGFs) protected neurons from H2O2-induced
      oxidative stress and indicated the involvement of PI3K-Akt and MAP kinases as an
      underlying mechanism. Ca(2+) overload has been shown to mediate the neurotoxic
      effects of oxidative stress and excitotoxicity. We examined the effects of PDGFs
      on H2O2-induced Ca(2+) overload in primary cultured neurons to further clarify
      their neuroprotective mechanism. H2O2-induced Ca(2+) overload in neurons in a
      dose-dependent manner, while pretreating neurons with PDGF-BB for 24 hours
      largely suppressed it. In a comparative study, the suppressive effects of PDGF-BB
      were more potent than those of PDGF-AA. We then evaluated calpain activation,
      which was induced by Ca(2+) overload and mediated both apoptotic and nonapoptotic
      cell death. H2O2-induced calpain activation in neurons in a dose-dependent
      manner. Pretreatment of PDGF-BB completely blocked H2O2-induced calpain
      activation. To the best of our knowledge, the present study is the first to
      demonstrate the mechanism underlying the neuroprotective effects of PDGF against
      oxidative stress via the suppression of Ca(2+) overload and inactivation of
      calpain and suggests that PDGF-BB may be a potential therapeutic target of
      neurological diseases. 

PMID- 24454982
TI  - Differential microRNA profiling in a cellular hypoxia reoxygenation model upon
      posthypoxic propofol treatment reveals alterations in autophagy signaling
      network.
AB  - Recent studies indicate that propofol may protect cells via suppressing
      autophagic cell death caused by excessive reactive oxygen species induced by
      hypoxia reoxygenation (H/R). It is established that gene expression patterns
      including autophagy-related genes changed significantly during the process of H/R
      in the presence or absence of propofol posthypoxia treatment (P-PostH). The
      reasons for such differences, however, remain largely unknown. MicroRNAs provide
      a novel mechanism for gene regulation. In the present study, we systematically
      analyzed the alterations in microRNA expression using human umbilical vein
      endothelial cells (HUVECs) subjected to H/R in the presence or absence of
      posthypoxic propofol treatment. Genome-wide profiling of microRNAs was then
      conducted using microRNA microarray. Fourteen miRNAs are differentially expressed
      and six of them were validated by the quantitative real-time PCR (Q-PCR) of which
      three were substantially increased, whereas one was decreased. To gain an
      unbiased global perspective on subsequent regulation by altered miRNAs, predicted
      targets of ten miRNAs were analyzed using the Gene Ontology (GO) analysis to
      build signaling networks. Interestingly, six of the identified microRNAs are
      known to target autophagy-related genes. In conclusion, our results revealed that
      different miRNA expression patterns are induced by propofol posthypoxia treatment
      in H/R and the alterations in miRNA expression patterns are implicated in
      regulating distinctive autophagy-related gene expression. 

PMID- 24454983
TI  - Proteomic analysis of plasma-purified VLDL, LDL, and HDL fractions from
      atherosclerotic patients undergoing carotid endarterectomy: identification of
      serum amyloid A as a potential marker.
AB  - Apolipoproteins are very heterogeneous protein family, implicated in plasma
      lipoprotein structural stabilization, lipid metabolism, inflammation, or
      immunity. Obtaining detailed information on apolipoprotein composition and
      structure may contribute to elucidating lipoprotein roles in atherogenesis and to
      developing new therapeutic strategies for the treatment of lipoprotein-associated
      disorders. This study aimed at developing a comprehensive method for
      characterizing the apolipoprotein component of plasma VLDL, LDL, and HDL
      fractions from patients undergoing carotid endarterectomy, by means of two
      dimensional electrophoresis (2-DE) coupled with Mass Spectrometry analysis,
      useful for identifying potential markers of plaque presence and vulnerability.
      The adopted method allowed obtaining reproducible 2-DE maps of exchangeable
      apolipoproteins from VLDL, LDL, and HDL. Twenty-three protein isoforms were
      identified by peptide mass fingerprinting analysis. Differential proteomic
      analysis allowed for identifying increased levels of acute-phase serum amyloid A
      protein (AP SAA) in all lipoprotein fractions, especially in LDL from
      atherosclerotic patients. Results have been confirmed by western blotting
      analysis on each lipoprotein fraction using apo AI levels for data normalization.
      The higher levels of AP SAA found in patients suggest a role of LDL as AP SAA
      carrier into the subendothelial space of artery wall, where AP SAA accumulates
      and may exert noxious effects. 

PMID- 24454984
TI  - The protection of salidroside of the heart against acute exhaustive injury and
      molecular mechanism in rat.
AB  - OBJECTIVE: To investigate the protection of salidroside of the heart against
      acute exhaustive injury and its mechanism of antioxidative stress and MAPKs
      signal transduction. METHOD: Adult male SD rats were divided into four groups
      randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and
      transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD
      were determined by ELISA method, and the phosphorylation degrees of ERK and p38
      MAPK were assayed by Western blotting. Cardiac function of isolated rat heart
      ischemia/reperfusion was detected by Langendorff technique. RESULTS: Salidroside
      reduced the myocardium ultrastructure injury caused by exhaustive swimming,
      decreased the contents of CK, CK-MB, and LDH, improved the LVDP, +/-LV dp/dt(max)
      under the basic condition, reduced the content of MDA and the phosphorylation
      degree of p38 MAPK, and increased the content of SOD and the phosphorylation
      degree of ERK in acute exhaustive rats. CONCLUSION: Salidroside has the
      protection of the heart against acute exhaustive injury. The cardioprotection is
      mainly mediated by antioxidative stress and MAPKs signal transduction through
      reducing the content of MDA, increasing the content of SOD, and increasing p-ERK
      and decreasing p-p38 protein expressions in rat myocardium, which might be the
      mechanisms of the cardioprotective effect of salidroside.

PMID- 24454985
TI  - Relation between gastric cancer and protein oxidation, DNA damage, and lipid
      peroxidation.
AB  - OBJECTS: The aim of this study is to evaluate protein oxidation, DNA damage, and
      lipid peroxidation in patients with gastric cancer and to investigate the
      relationship between oxidative stress and gastric cancer. METHODS: We
      investigated changes in serum protein carbonyl (PC), advanced oxidation protein
      products (AOPP), and 3-nitrotyrosine (3-NT) levels, as indicators of protein
      oxidation, serum 8-hydroxydeoxyguanosine (8-OHdG), as a biomarker of DNA damage,
      and malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), and 8
      ISO-prostaglandin F2alpha (8-PGF) in serum, as lipid peroxidation markers in
      gastric cancer (GC) patients and healthy control. RESULTS: Compared with control,
      a statistically significant higher values of 8-OHdG, PC, AOPP, and 3-NT were
      observed in the GC patients (P < 0.05). The products of lipid peroxidation, MDA,
      CD, 4-HNE, and 8-PGF, were significantly lower in the GC patients compared to
      those of control (P < 0.05). In addition, the products of oxidative stress were
      similar between the Helicobacter pylori positive and the negative subgroups of GC
      patients. CONCLUSIONS: GC patients were characterized by increased protein
      oxidation and DNA damage, and decreased lipid peroxidation. Assessment of
      oxidative stress and augmentation of the antioxidant defense system may be
      important for the treatment and prevention of gastric carcinogenesis.

PMID- 24454986
TI  - Modulation of antioxidant enzymatic activities by certain antiepileptic drugs
      (valproic acid, oxcarbazepine, and topiramate): evidence in humans and
      experimental models.
AB  - It is estimated that at least 100 million people worldwide will suffer from
      epilepsy at some point in their lives. This neurological disorder induces brain
      death due to the excessive liberation of glutamate, which activates the
      postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the
      reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a
      series of events leading to nitric oxide synthase (NOS) activation and the
      generation of reactive oxygen species (ROS). Several studies in experimental
      models and in humans have demonstrated that certain antiepileptic drugs (AEDs)
      exhibit antioxidant effects by modulating the activity of various enzymes
      associated with this type of stress. Considering the above-mentioned data, we
      aimed to compile evidence elucidating how AEDs such as valproic acid (VPA),
      oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. 

PMID- 24454987
TI  - Mild systemic oxidative stress in the subclinical stage of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a late-onset, progressive degenerative disorder that
      affects mainly the judgment, emotional stability, and memory domains. AD is the
      outcome of a complex interaction among several factors which are not fully
      understood yet; nevertheless, it is clear that oxidative stress and inflammatory
      pathways are among these factors. 65 elderly subjects (42 cognitively intact and
      23 with probable Alzheimer's disease) were selected for this study. We evaluated
      erythrocyte activities of superoxide dismutase, catalase, and glutathione
      peroxidase as well as plasma levels of total glutathione, alpha-tocopherol, beta
      carotene, lycopene, and coenzyme Q10. These antioxidant parameters were
      confronted with plasmatic levels of protein and lipid oxidation products.
      Additionally, we measured basal expression of monocyte HLA-DR and CD-11b, as well
      as monocyte production of cytokines IL1-alpha, IL-6, and TNF-alpha. AD patients
      presented lower plasmatic levels of alpha-tocopherol when compared to control
      ones and also higher basal monocyte HLA-DR expression associated with higher IL
      1alpha production when stimulated by LPS. These findings support the inflammatory
      theory of AD and point out that this disease is associated with a higher basal
      activation of circulating monocytes that may be a result of alpha-tocopherol
      stock depletion.

PMID- 24454988
TI  - Moringa oleifera mitigates memory impairment and neurodegeneration in animal
      model of age-related dementia.
AB  - To date, the preventive strategy against dementia is still essential due to the
      rapid growth of its prevalence and the limited therapeutic efficacy. Based on the
      crucial role of oxidative stress in age-related dementia and the antioxidant and
      nootropic activities of Moringa oleifera, the enhancement of spatial memory and
      neuroprotection of M. oleifera leaves extract in animal model of age-related
      dementia was determined. The possible underlying mechanism was also investigated.
      Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves
      extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7
      days after the intracerebroventricular administration of AF64A bilaterally. Then,
      they were assessed memory, neuron density, MDA level, and the activities of SOD,
      CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract
      improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus
      of hippocampus together with the decreased MDA level and AChE activity but
      increased SOD and CAT activities. Therefore, our data suggest that M. oleifera
      leaves extract is the potential cognitive enhancer and neuroprotectant. The
      possible mechanism might occur partly via the decreased oxidative stress and the
      enhanced cholinergic function. However, further explorations concerning active
      ingredient(s) are still required.

PMID- 24454989
TI  - Astragalus polysaccharide suppresses skeletal muscle myostatin expression in
      diabetes: involvement of ROS-ERK and NF-kappaB pathways.
AB  - OBJECTIVE: The antidiabetes drug astragalus polysaccharide (APS) is capable of
      increasing insulin sensitivity in skeletal muscle and improving whole-body
      glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth
      factor myostatin plays an important role in regulating insulin signaling and
      insulin resistance. We hypothesized that regulation of skeletal muscle myostatin
      expression may be involved in the improvement of insulin sensitivity by APS.
      METHODS: APS was administered to 13-week-old diabetic KKAy and nondiabetic
      C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the
      saturated acid palmitate-induced insulin resistance and myostatin expression in
      C2C12 cells. RESULTS: APS treatment ameliorated hyperglycemia, hyperlipidemia,
      and insulin resistance and decreased the elevation of myostatin expression and
      malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic
      KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired
      glucose uptake, overproduction of ROS, activation of extracellular regulated
      protein kinases (ERK), and NF-kappaB were partially restored by APS treatment.
      The protective effects of APS were mimicked by ERK and NF-kappaB inhibitors,
      respectively. CONCLUSION: Our study demonstrates elevated myostatin expression in
      skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed
      to palmitate. APS is capable of improving insulin sensitivity and decreasing
      myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-kappaB
      pathway.

PMID- 24454990
TI  - Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin
      induced toxicity in primary cultures of cerebellar granule neurons of rats.
AB  - Curcumin is a bifunctional antioxidant derived from Curcuma longa. This study
      identifies curcumin as a neuroprotectant against hemin-induced damage in primary
      cultures of cerebellar granule neurons (CGNs) of rats. Hemin, the oxidized form
      of heme, is a highly reactive compound that induces cellular injury. Pretreatment
      of CGNs with 5-30 MUM curcumin effectively increased by 2.3-4.9 fold heme
      oxygenase-1 (HO-1) expression and by 5.6-14.3-fold glutathione (GSH) levels.
      Moreover, 15 MUM curcumin attenuated by 55% the increase in reactive oxygen
      species (ROS) production, by 94% the reduction of GSH/glutathione disulfide
      (GSSG) ratio, and by 49% the cell death induced by hemin. The inhibition of heme
      oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine
      sulfoximine, respectively, suppressed the protective effect of curcumin against
      hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a
      major role in the protective effect of curcumin. Furthermore, it was found that
      24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the
      activity of glutathione reductase, glutathione S-transferase and superoxide
      dismutase, respectively. Additionally, it was found that curcumin was capable of
      inducing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into
      the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2
      and an antioxidant response that may play an important role in the protective
      effect of this antioxidant against hemin-induced neuronal death.

PMID- 24454993
TI  - Discovery of beta2 Adrenergic Receptor Ligands Using Biosensor Fragment Screening
      of Tagged Wild-Type Receptor.
AB  - G-protein coupled receptors (GPCRs) are the primary target class of currently
      marketed drugs, accounting for about a quarter of all drug targets of approved
      medicines. However, almost all the screening efforts for novel ligand discovery
      rely exclusively on cellular systems overexpressing the receptors. An alternative
      ligand discovery strategy is a fragment-based drug discovery, where low molecular
      weight compounds, known as fragments, are screened as initial starting points for
      optimization. However, the screening of fragment libraries usually employs
      biophysical screening methods, and as such, it has not been routinely applied to
      membrane proteins. We present here a surface plasmon resonance biosensor approach
      that enables, cell-free, label-free, fragment screening that directly measures
      fragment interactions with wild-type GPCRs. We exemplify the method by the
      discovery of novel, selective, high affinity antagonists of human beta2
      adrenoceptor.

PMID- 24454994
TI  - Defining the scholarly and scholarship common program requirements.

PMID- 24454991
TI  - Phytoagents for cancer management: regulation of nucleic acid oxidation, ROS, and
      related mechanisms.
AB  - Accumulation of oxidized nucleic acids causes genomic instability leading to
      senescence, apoptosis, and tumorigenesis. Phytoagents are known to reduce the
      risk of cancer development; whether such effects are through regulating the
      extent of nucleic acid oxidation remains unclear. Here, we outlined the role of
      reactive oxygen species in nucleic acid oxidation as a driving force in cancer
      progression. The consequential relationship between genome instability and cancer
      progression highlights the importance of modulation of cellular redox level in
      cancer management. Current epidemiological and experimental evidence demonstrate
      the effects and modes of action of phytoagents in nucleic acid oxidation and
      provide rationales for the use of phytoagents as chemopreventive or therapeutic
      agents. Vitamins and various phytoagents antagonize carcinogen-triggered
      oxidative stress by scavenging free radicals and/or activating endogenous defence
      systems such as Nrf2-regulated antioxidant genes or pathways. Moreover, metal ion
      chelation by phytoagents helps to attenuate oxidative DNA damage caused by
      transition metal ions. Besides, the prooxidant effects of some phytoagents pose
      selective cytotoxicity on cancer cells and shed light on a new strategy of cancer
      therapy. The "double-edged sword" role of phytoagents as redox regulators in
      nucleic acid oxidation and their possible roles in cancer prevention or therapy
      are discussed in this review. 

PMID- 24454992
TI  - Health promoting effects of brassica-derived phytochemicals: from chemopreventive
      and anti-inflammatory activities to epigenetic regulation.
AB  - A high intake of brassica vegetables may be associated with a decreased chronic
      disease risk. Health promoting effects of Brassicaceae have been partly
      attributed to glucosinolates and in particular to their hydrolyzation products
      including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive
      activity of isothiocyanates through the redox-sensitive transcription factor
      Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in
      humans support an anti-inflammatory effect of brassica-derived phytochemicals.
      However, the underlying mechanisms of how these compounds mediate their health
      promoting effects are yet not fully understood. Recent findings suggest that
      brassica-derived compounds are regulators of epigenetic mechanisms. It has been
      shown that isothiocyanates may inhibit histone deacetylase transferases and DNA
      methyltransferases in cultured cells. Only a few papers have dealt with the
      effect of brassica-derived compounds on epigenetic mechanisms in laboratory
      animals, whereas data in humans are currently lacking. The present review aims to
      summarize the current knowledge regarding the biological activities of brassica
      derived phytochemicals regarding chemopreventive, anti-inflammatory, and
      epigenetic pathways. 

PMID- 24454995
TI  - Analyzing and interpreting data from likert-type scales.

PMID- 24454996
TI  - Fixing the primary care pipeline: the role of teaching health centers.

PMID- 24454997
TI  - The "hateful resident".

PMID- 24454998
TI  - Medical errors: teachable moments in doing the right thing.

PMID- 24454999
TI  - Are duty hour regulations promoting a culture of dishonesty among resident
      physicians?

PMID- 24455000
TI  - Rural primary care physician workforce expansion: an opportunity for bipartisan
      legislation.

PMID- 24455001
TI  - Can we make grand rounds "grand" again?

PMID- 24455002
TI  - Resident scholarship expectations and experiences: sources of uncertainty as
      barriers to success.
AB  - BACKGROUND: Scholarly activity during residency is vital to resident learning and
      ultimately to patient care. Incorporating that activity into training is,
      however, a challenge for medical educators. Most research on medical student and
      resident attitudes toward scholarly activity to date has been quantitative and
      has focused on level of interest, desire to perform scholarship, and perceived
      importance of scholarship. OBJECTIVE: We explored attitudes, expectations, and
      barriers regarding participation in scholarly activity among current residents
      and graduates of a single family medicine residency program. METHODS: Using a
      phenomenologic approach, we systematically analyzed data from one-on-one,
      semistructured interviews with residents and graduates. Interviews included
      participant expectations and experiences with scholarly activity in residency.
      RESULTS: The 20 participants (residents, 15 [75%]; residency graduates, 5 [25%])
      identified uncertainty in their attitudes toward, and expectations regarding,
      participation in scholarly activity as an overarching theme, which may present a
      barrier to participation. Themes included uncertainty regarding their personal
      identity as a clinician, time to complete scholarly activity, how to establish a
      mentor-mentee relationship, the social norms of scholarship, what counted toward
      the scholarship requirements, the protocol for completing projects, and the
      clinical relevance of scholarship. CONCLUSIONS: Uncertainty about scholarly
      activity expectations can add to learner anxiety and make performing scholarly
      activity during residency seem like an insurmountable task. Programs should
      consider implementing a variety of strategies to foster scholarly activity during
      residency, including clarifying and codifying expectations and facilitating
      mentoring relationships with faculty.

PMID- 24455003
TI  - Development of the objective, structured communication assessment of residents
      (OSCAR) tool for measuring communication skills with patients.
AB  - BACKGROUND: Although interpersonal and communication skills are essential to
      physician practice, there is a dearth of effective tools to meaningfully teach
      and assess communication skills. OBJECTIVE: The purpose of our study was to
      create a standardized tool for evaluation of communication skills for residents
      across specialties. METHODS: We designed an Objective, Structured Communication
      Assessment of Residents (OSCAR) tool, consisting of 4 clinical stations, to
      assess intern communication skills with relationship development, their
      establishment of case goals, and their organization and time management skills.
      Interns from 11 training programs completed the stations, with senior residents
      trained to function as standardized patients. The 4 stations' scenarios were a
      disruptive patient, handling a phone call for a narcotics refill, disclosing a
      medical mistake, and delivering bad news. RESULTS: Eighty-three interns completed
      OSCAR during orientation. The assessment took interns about 40 minutes to
      complete, and participants were given immediate feedback by the standardized
      patients. The total possible score for each station was 50. Resident performance
      was highest for disclosing a medical error (94%, 47 of 50), followed by handling
      a disruptive patient (90%, 45 of 50), disclosing bad news (86%, 43 of 50), and
      handling the phone call for the narcotics refill (62%, 31 of 50). Multivariate
      analysis of variance results indicated differences between residents from US and
      international medical schools, but there were no significant differences across
      specialties. Interrater reliability was excellent for each station (> 0.80).
      CONCLUSIONS: OSCAR is a practical tool for assessing interns' communication
      skills to provide timely results to program directors.

PMID- 24455004
TI  - Understanding the impact of residents' interpersonal relationships during
      emergency department referrals and consultations.
AB  - BACKGROUND: Communicating with colleagues is a key physician competency. Yet few
      studies have sought to uncover the complex nature of relationships between
      referring and consulting physicians, which may be affected by the inherent
      relationships between the participants. OBJECTIVE: Our study examines themes
      identified from discussions about communications and the role of relationships
      during the referral-consultation process. METHODS: From March to September 2010,
      30 residents (10 emergency medicine, 10 general surgery, 10 internal medicine)
      were interviewed using a semistructured focus group protocol. Two investigators
      independently reviewed the transcripts using inductive methods and grounded
      theory to generate themes (using codes for ease of analysis) until saturation was
      reached. Disagreements were resolved by consensus, yielding an inventory of
      themes and subthemes. Measures for ensuring trustworthiness of the analysis
      included generating an audit trail and external auditing of the material by
      investigators not involved with the initial analysis. RESULTS: Two main
      relationship-related themes affected the referral-consultation process:
      familiarity and trust. Various subthemes were further delineated and studied in
      the context of pertinent literature. CONCLUSIONS: Relationships between
      physicians have a powerful influence on the emergency department referral
      consultation dynamic. The emergency department referral-consultation may be
      significantly altered by the familiarity and perceived trustworthiness of the
      referring and consulting physicians. Our proposed framework may further inform
      and improve instructional methods for teaching interpersonal communication. Most
      importantly, it may help junior learners understand inherent difficulties they
      may encounter during the referral process between emergency and consulting
      physicians.

PMID- 24455005
TI  - The relationship between faculty performance assessment and results on the in
      training examination for residents in an emergency medicine training program.
AB  - BACKGROUND: Medical knowledge (MK) in residents is commonly assessed by the in
      training examination (ITE) and faculty evaluations of resident performance.
      OBJECTIVE: We assessed the reliability of clinical evaluations of residents by
      faculty and the relationship between faculty assessments of resident performance
      and ITE scores. METHODS: We conducted a cross-sectional, observational study at
      an academic emergency department with a postgraduate year (PGY)-1 to PGY-3
      emergency medicine residency program, comparing summative, quarterly, faculty
      evaluation data for MK and overall clinical competency (OC) with annual ITE
      scores, accounting for PGY level. We also assessed the reliability of faculty
      evaluations using a random effects, intraclass correlation analysis. RESULTS: We
      analyzed data for 59 emergency medicine residents during a 6-year period. Faculty
      evaluations of MK and OC were highly reliable (kappa  =  0.99) and remained
      reliable after stratification by year of training (mean kappa  =  0.68-0.84).
      Assessments of resident performance (MK and OC) and the ITE increased with PGY
      level. The MK and OC results had high correlations with PGY level, and ITE scores
      correlated moderately with PGY. The OC and MK results had a moderate correlation
      with ITE score. When residents were grouped by PGY level, there was no
      significant correlation between MK as assessed by the faculty and the ITE score.
      CONCLUSIONS: Resident clinical performance and ITE scores both increase with
      resident PGY level, but ITE scores do not predict resident clinical performance
      compared with peers at their PGY level.

PMID- 24455006
TI  - The learners' perceptions survey-primary care: assessing resident perceptions of
      internal medicine continuity clinics and patient-centered care.
AB  - BACKGROUND: In 2010, the Department of Veterans Affairs (VA) implemented a
      national patient-centered care initiative that organized primary care into
      interdisciplinary teams of health care professionals to provide patient-centered,
      continuous, and coordinated care. OBJECTIVE: We assessed the discriminate
      validity of the Learners' Perceptions Survey-Primary Care (LPS-PC), a tool
      designed to measure residents' perceptions about their primary and patient
      centered care experiences. METHODS: Between October 2010 and June 2011, the LPS
      PC was administered to Loma Linda University Medical Center internal medicine
      residents assigned to continuity clinics at the VA Loma Linda Healthcare System
      (VALLHCS), a university setting, or the county hospital. Adjusted differences in
      satisfaction ratings across settings and over domains (patient- and family
      centered care, faculty and preceptors, learning, clinical, work and physical
      environments, and personal experience) were computed using a generalized linear
      model. RESULTS: Our response rate was 86% (77 of 90). Residents were more
      satisfied with patient- and family-centered care at the VALLHCS than at either
      the university or county (P < .001). However, faculty and preceptors (odds ratio
      [OR]  =  1.53), physical (OR  =  1.29), and learning (OR  =  1.28) environments
      had more impact on overall resident satisfaction than patient- and family
      centered care (OR  =  1.08). CONCLUSIONS: The LPS-PC demonstrated discriminate
      validity to assess residents' perceptions of their patient-centered clinical
      training experience across outpatient primary care settings at an internal
      medicine residency program. The largest difference in scores was the patient- and
      family-centered care domain, in which residents rated the VALLHCS much higher
      than the university or county sites.

PMID- 24455007
TI  - Leading educationally effective family-centered bedside rounds.
AB  - BACKGROUND: Family-centered bedside rounds (family-centered rounds) enable
      learning and clinical care to occur simultaneously and offer benefits to
      patients, health care providers, and multiple levels of learners. OBJECTIVE: We
      used a qualitative approach to understand the dimensions of successful (ie,
      educationally positive) family-centered rounds from the perspective of attending
      physicians and residents. METHODS: We studied rounds in a tertiary academic
      hospital affiliated with the University of Calgary. Data were collected from 7
      focus groups of pediatrics residents and attendings and were analyzed using
      grounded theory. RESULTS: Attending pediatricians and residents described rounds
      along a spectrum from successful and highly educational to unsuccessful and of
      low educational value. Perceptions of residents and attendings were influenced by
      how well the environment, educational priorities, and competing priorities were
      managed. Effectiveness of the manager was the core variable for successful rounds
      led by persons who could develop predictable rounds and minimize learner
      vulnerability. CONCLUSIONS: Success of family-centered rounds in teaching
      settings depended on making the education and patient care aims of rounds
      explicit to residents and attending faculty. The role of the manager in leading
      rounds also needs to be made explicit.

PMID- 24455008
TI  - Paperwork versus patient care: a nationwide survey of residents' perceptions of
      clinical documentation requirements and patient care.
AB  - BACKGROUND: The current health care system requires a substantial amount of
      documentation by physicians, potentially limiting time spent on patient care.
      OBJECTIVE: We sought to explore trainees' perceptions of their clinical
      documentation requirements and the relationship between time spent on clinical
      documentation versus time available for patient care. METHODS: An anonymous,
      online survey was sent to trainees in all postgraduate years of training and
      specialties in Accreditation Council for Graduate Medical Education-accredited
      programs. RESULTS: Over a 2-month time frame, 1515 trainees in 24 specialties
      completed the survey. Most (92%) reported that documentation obligations are
      excessive, that time spent with patients has been compromised by this (90%), and
      that the amount of clinical documentation has had a negative effect on patient
      care (73%). Most residents and fellows reported feeling rushed and frustrated
      because of these documentation demands. They also reported that time spent on
      these tasks decreased their time available for teaching others and reduced the
      quality of their education. Respondents reported spending more time on clinical
      documentation than on direct patient care (P < .001). CONCLUSIONS: Trainees'
      current clinical documentation workload may be a barrier to optimal patient care
      and to resident and fellow education. Residents and fellows report that clinical
      documentation duties are onerous, and there is a perceived negative effect on
      time spent with patients, overall quality of patient care, physician well-being,
      time available for teaching, and quality of resident education.

PMID- 24455009
TI  - Filling the void: defining invasive bedside procedural competency for internal
      medicine residents.
AB  - BACKGROUND: Residents perform invasive bedside procedures in most training
      programs. To date, there is no universal approach for determining competency and
      ensuring quality and safety of care. OBJECTIVE: We developed and implemented an
      assessment of central venous catheter insertion competency for internal medicine
      and internal medicine-pediatrics residents, using measurements for knowledge,
      skill, and attitude and linking them to procedural outcomes. METHODS: We
      conducted a cohort study of a 4-week, resident-run procedure service from July
      2007 through June 2011 at a large academic medical center. Knowledge was assessed
      by using a written test, technical skill by using a checklist, and attitude by
      self- and supervisor assessments of residents' confidence and capability.
      Competence was defined as (1) a minimum written test score (70%); (2) a perfect
      checklist score; (3) a resident's self-assessed confidence and capability scores
      of 4 or 5 of 5; and (4) faculty rating of the resident's confidence and
      capability as 5 of 5. A composite success rate was based on procedural outcomes
      (eg, completed procedures, less than 3 forward needle passes, and complication
      rate) and was compared to the checklist scores. RESULTS: A total of 148 internal
      medicine and medicine-pediatrics residents inserted 639 catheters, and 53 (36%)
      achieved competence by the end of 4 weeks. Residents judged to be competent by
      checklist scores had a higher composite success rate than those deemed not
      competent. CONCLUSIONS: Our multi-factorial criteria used to define central
      venous catheter insertion competency effectively discriminated between residents
      judged to be competent and those judged not competent, using data from procedural
      outcomes.

PMID- 24455010
TI  - Impact of simulation training on time to initiation of cardiopulmonary
      resuscitation for first-year pediatrics residents.
AB  - BACKGROUND: Pediatrics residents have few opportunities to perform
      cardiopulmonary resuscitation (CPR). Enhancing the quality of CPR is a key factor
      to improving outcomes for cardiopulmonary arrest in children and requires
      effective training strategies. OBJECTIVE: To evaluate the effectiveness of a
      simulation-based intervention to reduce first-year pediatrics residents' time for
      3 critical actions in CPR: (1) call for help, (2) initiate bag-mask ventilation,
      and (3) initiate chest compressions. METHODS: A prospective study involving 31
      first-year pediatrics residents at a children's hospital assigned to an early or
      late (control) intervention group. Residents underwent baseline assessment
      followed by repeat evaluations at 3 and 6 months. Time to critical actions was
      scored by video review. A 90-minute educational intervention focused on skill
      practice was conducted following baseline evaluation for the early-intervention
      group and following 3-month evaluation for the late-intervention group. Primary
      outcome was change in time to initiating the 3 critical actions. Change in time
      was analyzed by comparison of Kaplan-Meier curves, using the log-rank test. A 10%
      sample was timed by a second rater. Agreement was assessed using intraclass
      correlation (ICC). RESULTS: There was a statistically significant reduction in
      time for all 3 critical actions between baseline and 3-month evaluation in the
      early intervention group; this was not observed in the late (control) group.
      Rater agreement was excellent (ICC >= 0.99). CONCLUSIONS: A simulation-based
      educational intervention significantly reduced time to initiation of CPR for
      first-year pediatrics residents. Simulation training facilitated acquisition of
      critical CPR skills that have the potential to impact patient outcome.

PMID- 24455011
TI  - Effect of resident evaluations of obstetrics and gynecology faculty on promotion.
AB  - BACKGROUND: Promotion for academic faculty depends on a variety of factors,
      including their research, publications, national leadership, and quality of their
      teaching. OBJECTIVE: We sought to determine the importance of resident
      evaluations of faculty for promotion in obstetrics-gynecology programs. METHODS:
      A 28-item questionnaire was developed and distributed to 185 department chairs of
      US obstetrics-gynecology residency programs. RESULTS: Fifty percent (93 of 185)
      responded, with 40% (37 of 93) stating that teaching has become more important
      for promotion in the past 10 years. When faculty are being considered for
      promotion, teaching evaluations were deemed "very important" 60% of the time for
      clinician track faculty but were rated as mainly "not important" or "not
      applicable" for research faculty. Sixteen respondents (17%) stated a faculty
      member had failed to achieve promotion in the past 5 years because of poor
      teaching evaluations. Positive teaching evaluations outweighed low publication
      numbers for clinical faculty 24% of the time, compared with 5% for research
      faculty and 8% for tenured faculty being considered for promotion. The most
      common reason for rejection for promotion in all tracks was the number of
      publications. Awards for excellence in teaching improved chances of promotion.
      CONCLUSIONS: Teaching quality is becoming more important in academic obstetrics
      gynecology departments, especially for clinical faculty. Although in most
      institutions promotion is not achieved without adequate research and
      publications, the importance of teaching excellence is obvious, with 1 of 6 (17%)
      departments reporting a promotion had been denied due to poor teaching
      evaluations.

PMID- 24455012
TI  - The surgical residency baby boom: changing patterns of childbearing during
      residency over a 30-year span.
AB  - BACKGROUND: Birthrates during surgical residency appear to be rising. One
      assumption is that this is due to changes in the structure of surgical
      residencies. OBJECTIVE: The purpose of our study was to explore whether an
      increase in birthrates has occurred and the reasons for this. METHODS: We
      conducted an anonymous survey of current residents and alumni from 1976 to 2009
      at a single university-based surgery training program. RESULTS: Alumni (46 of
      116) and current residents (38 of 51) were surveyed, and our response rate was
      approximately 50% (84 of 167). Respondents were grouped into cohorts based on
      their residency start year. The early cohort consisted of residents starting
      residency between 1976 and 1999, and the late cohort consisted of residents
      starting residency between 2000 and 2009. The percentage of male residents with
      children during residency training was similar for the early and late cohorts
      (34% [10 of 29] versus 41% [9 of 22]). For female residents, there was a
      substantial increase in childbearing for the late cohort (7% [1 of 15] versus 35%
      [6 of 18]). Fifty-two percent (44 of 84) of the respondents who had children
      during residency reported that work hours and schedule had a negative effect on
      their decision to have children. Most respondents reported that availability or
      cost of child care, impact on residency, support from the program, increased
      length of training, or availability of family leave did not factor as concerns.
      CONCLUSIONS: Childbearing during residency has increased in female residents in
      our study. Surgical residency programs may need to accommodate this change if
      they want to continue to recruit and retain talented residents.

PMID- 24455013
TI  - Accuracy of residents' retrospective perceptions of 16-hour call admitting shift
      compliance and characteristics.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education Resident
      Fellow Survey measurement of compliance with duty hours uses remote retrospective
      resident report, the accuracy of which has not been studied. We investigated
      residents' remote recall of 16-hour call-shift compliance and workload
      characteristics at 1 institution. METHODS: We sent daily surveys to second- and
      third-year internal medicine residents immediately after call shifts from July
      2011 to June 2012 to assess compliance with 16-hour shift length and workload
      characteristics. In June 2012, we sent a survey with identical items to assess
      residents' retrospective perceptions of their call-shift compliance and workload
      characteristics over the preceding year. We used linear models to compare on-call
      data to residents' retrospective data. RESULTS: We received a survey response
      from residents after 497 of 648 call-shifts (77% response). The end-of-year
      perceptions survey was completed by 87 of 95 residents (92%). Compared with on
      call data, the recollections of 5 (6%) residents were accurate; however, 48 (56%)
      underestimated and 33 (38%) overestimated compliance with the 16-hour shift
      length requirement. The average magnitude of under- and overestimation was 18%
      (95% confidence interval  =  13-23). Using a greater than 10% absolute difference
      to define under- and overestimation, 39 (45%) respondents were found to be
      accurate, 27 (31%) underestimated compliance, and 20 (23%) overestimated
      compliance. Residents overestimated census size, long call admissions, and
      admissions after 5 pm. CONCLUSIONS: Internal medicine residents' remote
      retrospective reporting of compliance with the 16-hour limit on continuous duty
      and workload characteristics was inaccurate compared with their immediate recall
      and included errors of underestimation and overestimation.

PMID- 24455014
TI  - Napping on the Night Shift: A Study of Sleep, Performance, and Learning in
      Physicians-in-Training.
AB  - BACKGROUND: Physicians in training experience fatigue from sleep loss, high
      workload, and working at an adverse phase of the circadian rhythm, which
      collectively degrades task performance and the ability to learn and remember. To
      minimize fatigue and sustain performance, learning, and memory, humans generally
      need 7 to 8 hours of sleep in every 24-hour period. METHODS: In a naturalistic,
      within-subjects design, we studied 17 first- and second-year internal medicine
      residents working in a tertiary care medical center, rotating between day shift
      and night float every 4 weeks. We studied each resident for 2 weeks while he/she
      worked the day shift and for 2 weeks while he/she worked the night float,
      objectively measuring sleep by wrist actigraphy, vigilance by the Psychomotor
      Vigilance Task test, and visual-spatial and verbal learning and memory by the
      Brief Visuospatial Memory Test-Revised and the Rey Auditory-Verbal Learning Test.
      RESULTS: Residents, whether working day shift or night float, slept approximately
      7 hours in every 24-hour period. Residents, when working day shift, consolidated
      their sleep into 1 main sleep period at night. Residents working night float
      split their sleep, supplementing their truncated daytime sleep with nighttime on
      duty naps. There was no difference in vigilance or learning and memory, whether
      residents worked day shift or night float. CONCLUSIONS: Off-duty sleep
      supplemented with naps while on duty appears to be an effective strategy for
      sustaining vigilance, learning, and memory when working night float.

PMID- 24455015
TI  - A longitudinal career-focused block for third-year pediatrics residents.
AB  - BACKGROUND: The traditional 1-month training blocks in pediatrics may fail to
      provide sufficient exposure to develop the knowledge, skills, and attitudes
      residents need for practice and may not be conducive to mentoring relationships
      with faculty and continuity with patients. INTERVENTION: We created a 4-month
      career-focused experience (CFE) for third-year residents. The CFE included block
      time and longitudinal experiences in different content areas related to
      residents' choice of urban and rural primary care, hospitalist medicine, or
      subspecialty care (prefellowship). Content was informed by graduate surveys,
      focus groups with primary care pediatricians and hospitalists, and interviews
      with fellowship directors. Outcomes were assessed via before and after surveys of
      residents' attitudes and skills, assessment of skills with an objective
      structured clinical examination (OSCE), and interviews with residents and
      mentors. RESULTS: Twenty-three of 49 third-year residents took part in the first
      2 years of CFE. Two residents dropped out, leaving 21 who completed the 4-month
      experience (9 in primary care, 2 in hospitalist medicine, and 10 in a
      subspecialty). Residents reported improvement in their clinical skills, increased
      satisfaction with faculty mentoring and evaluation, and the ability to focus on
      what was important to their careers. OSCE performance did not differ between
      residents who completed the CFE and those who did not. Administrative burden was
      high. CONCLUSIONS: Four-month career-focused training for pediatrics residents is
      feasible and may be effective in meeting part of the new requirement for 6 months
      of career-focused training during pediatrics residency.

PMID- 24455016
TI  - Restructuring the orthopedic resident research curriculum to increase scholarly
      activity.
AB  - BACKGROUND: Limited time and funding are challenges to meeting the research
      requirement of the orthopedic residency curriculum. OBJECTIVE: We report a
      reorganized research curriculum that increases research quality and productivity
      at our academic orthopedic medical center. METHODS: Changes made to the
      curriculum, which began in 2006 and were fully phased in by 2008, included
      research milestones for each training year, a built-in support structure, use of
      an accredited bio-skills laboratory, mentoring by National Institutes of Health
      funded scientists, and protected time to engage in required research and prepare
      scholarly peer-reviewed publications. RESULTS: Total grant funding of resident
      research increased substantially, from $15,000 in 2007 (8 graduates) to $380,000
      in 2010 (9 graduates), and the number of publications also increased. The 12
      residents who graduated in 2005 published 16 papers from 2000 to 2006, compared
      to 84 papers published by the 9 residents who graduated in 2010. The approximate
      costs per year included $19,000 (0.3 full-time equivalent) for an academic
      research coordinator; $16,000 for resident travel to professional meetings;
      reimbursement for 213 faculty hours; and funding for resident salaries while on
      the research rotation, paid through the general hospital budget. CONCLUSIONS: The
      number of grants and peer-reviewed publications increased considerably after our
      residency research curriculum was reorganized to allow dedicated research time
      and improved mentoring and infrastructure.

PMID- 24455017
TI  - Standardizing and Evaluating Transitions of Care in the Era of Duty Hour Reform:
      One Institution's Resident-Led Effort.
AB  - BACKGROUND: Compliance with the Accreditation Council for Graduate Medical
      Education duty hour standards may necessitate more frequent transitions of
      patient responsibility. INTERVENTION: We created a multidisciplinary Patient
      Safety and Quality Council with a Task Force on Handoffs (TFH), engaging
      residents at a large, university-based institution. METHODS: The TFH identified
      core content of effective handoffs and patterned institutional content on the
      SIGNOUTT mnemonic. A web-based module highlighting core content was developed for
      institutional orientation of all trainees beginning summer 2011 to standardize
      handoff education. The TFH distributed handoff material and catalogued additional
      program initiatives in teaching and evaluating handoffs. A standard handoff
      evaluation tool, assessing content, culture, and communication, was developed and
      "preloaded" into the institution-wide electronic evaluation system to standardize
      evaluation. The TFH developed questions pertaining to handoffs for an annual
      institutional survey in 2011 and 2012. Acceptability of efforts was measured by
      program participation, and feasibility was measured by estimating time and
      financial costs. RESULTS: Programs found the TFH's efforts to improve handoffs
      acceptable; to date, 13 program-specific teaching initiatives have been
      implemented, and the evaluation tool is being used by 5 programs. Time
      requirements for TFH participants average 2 to 3 h/mo, and financial costs are
      minimal. More residents reported having education on handoffs (58% [388 of 668]
      versus 42% [263 of 625], P < .001) and receiving adequate signouts (69% [469 of
      680] versus 61% [384 of 625], P  =  .004) in the 2012 survey, compared with 2011.
      CONCLUSIONS: Use of a multispecialty resident leadership group to address
      content, education, and evaluation of handoffs was feasible and acceptable to
      most programs at a large, university-based institution.

PMID- 24455018
TI  - Establishing electronic health record competency testing for first-year
      residents.
AB  - BACKGROUND: Despite widespread use of electronic health records (EHRs), it is
      unclear whether residents possess the EHR skills to perform required tasks.
      OBJECTIVE: We assessed first-year residents' skills on specific EHR tasks.
      METHODS: Incoming residents were required to participate in EHR training before
      starting clinical rotations. The training team developed an assessment tool for
      19 EHR tasks. Senior residents used a structured template to assess interns.
      RESULTS: For ambulatory workflow skills, most participants (range, 70%-100%)
      demonstrated competence. The 3 skills for which interns needed the most
      assistance were (1) creating and routing a result note (17 of 68, 25%), (2)
      deleting a medication or changing a dose in reconciling medications (10 of 68,
      15%), and (3) finding results for the past 90 days (10 of 68, 15%). For inpatient
      workflow skills, most interns (range, 63%-100%) demonstrated competence. The 3
      skills in which interns needed the most assistance were (1) placing a referral
      order at discharge (23 of 68, 34%), (2) finding a temperature on a flow sheet and
      trending it over time (14 of 68, 21%), and (3) creating a discharge summary,
      having it reviewed, and forwarding it to the primary care physician (14 of 68,
      21%). CONCLUSIONS: Our results should help EHR training teams at other
      institutions to better understand the strengths and weakness of EHR training
      approaches and to target training on tasks with the greatest performance deficits
      as well as toward underperforming individuals or groups.

PMID- 24455019
TI  - Comparison of 3 dilation and evacuation technical skills models.
AB  - BACKGROUND: Simulation training may improve patient safety, decrease trainer and
      trainee anxiety, and reduce the number of cases needed for competency.
      Complications associated with dilation and evacuation (D&E) have been directly
      related to provider skill level, yet no low-fidelity model has been formally
      described or evaluated in the literature for second-trimester D&E training.
      OBJECTIVE: We report physicians' assessments of the realism of 3 D&E models to
      establish a composite training model. METHODS: We surveyed experienced providers
      at 2 national conferences to evaluate 3 D&E models and rate each model's
      components on a Likert scale. RESULTS: Fifty-five obstetrics-gynecology and
      family medicine physicians completed the survey. Most respondents rated 4
      components of 1 model as somewhat realistic or very realistic. The components
      rated highest were the fetal parts (82% [45 of 55]) and placenta (60% [30 of
      50]). This model was rated as more likely to be used in training by 80% (43 of
      54) of participants than the 2 other models, as rated by 28% (15 of 54) and 9% (5
      of 54) of participants. CONCLUSIONS: A model made from a plastic bottle
      containing a stuffed fabric form with detachable parts has tactile similarity to
      a D&E procedure and should be further developed for testing and training.

PMID- 24455020
TI  - GME Innovations Grant Program at the University of Michigan Health System
      Fostering Changes in Education and Clinical Care.
AB  - BACKGROUND: Changes in graduate medical education (GME) have resulted in
      curricula, goals and objectives, and assessment methods becoming more formal, yet
      there is little financial support for the educational research required to
      develop better teaching approaches and assessment tools. OBJECTIVE: We sought to
      encourage the development of new educational tools and assessment methods to
      improve the overall conduct of GME at the University of Michigan. INTERVENTION:
      The University of Michigan Health System has recently established a new
      educational grant that is designed to foster innovative educational research in
      GME. We describe the experience with a new and robust internal educational grant,
      including the source of funding, mechanisms for reviewing and assessing the
      proposals, the types of proposals that have currently been funded, and the effect
      and results of these studies on GME at the University of Michigan Health System.
      OUTCOMES: Projects funded by the grant have changed the curriculum in the
      involved programs, and many have resulted in sustained changes, including new
      methodologies in the simulation center, the development of an "academy" of
      faculty physicians with significant teaching expertise, and the creation of web
      based teaching and assessment tools for "just in time" learning, and have been
      disseminated at national meetings and in peer-reviewed journals. CONCLUSIONS: The
      GME Innovations Grant Program at the University of Michigan Health System has
      been successful to date, funding 11 proposals during the course of 6 years. Some
      of these proposals have resulted in permanent changes and additions to residency
      training programs.

PMID- 24455021
TI  - Resident physician perspectives on outpatient continuity of care.
AB  - BACKGROUND: The outpatient continuity clinic is an essential component of
      internal medicine residency programs, yet continuity of patient care in these
      clinics is suboptimal. Reasons for this discontinuity have been inadequately
      explored. OBJECTIVE: We sought to assess perceived factors contributing to
      discontinuity in trainee ambulatory clinics. METHODS: The study encompassed 112
      internal medicine residents at a large academic medical center in the Midwest. We
      conducted 2 hours of facilitated discussion with 18 small groups of residents.
      Residents were asked to reflect on factors that pose barriers to continuity in
      their ambulatory practice and potential mechanisms to reduce these barriers.
      Resident comments were transcribed and inductive analysis was performed to
      develop themes. We used these themes to derive recommendations for improving
      continuity of care in a resident ambulatory clinic. RESULTS: Key themes included
      an imbalance of clinic scheduling that favors access for patients with acute
      symptoms over continuity, clinic triage scripts that deemphasize continuity,
      inadequate communication among residents and faculty regarding shared patients,
      residents' inefficient use of nonphysician care resources, and a lack of shared
      values between patients and providers regarding continuity of care. CONCLUSIONS:
      The results offer important information that may be applied in iterative program
      changes to enhance continuity of care in resident clinics.

PMID- 24455022
TI  - A pilot curriculum to integrate community health into internal medicine residency
      training.
AB  - BACKGROUND: Public health training has become an important aspect of residency
      education. The Institute of Medicine recommends public health training for all
      resident physicians, and internal medicine educational milestones include general
      public health skills. OBJECTIVE: We sought to integrate community health into
      internal medicine residency training by developing a community health elective
      (CHE) curriculum. METHODS: We developed a 2-week CHE curriculum for internal
      medicine residents, featuring facilitated discussion sessions, clinical
      experience at health centers targeting medically underserved populations, and a
      culminating presentation. We evaluated our pilot curriculum using pre-elective
      and postelective course surveys with Likert-type questions. RESULTS: Of 150
      eligible residents, 32 (21%) enrolled in the elective. Nearly all participants
      (30 of 32, 94%) strongly agreed that learning about community health was an
      important part of their residency training. Residents' perceived competence at
      discharging hospital patients with follow-up at community health sites increased
      13-fold after taking the elective (P < .001). There was no increase in reported
      likelihood to practice in an underserved community or in primary care.
      CONCLUSIONS: The CHE addresses several Accreditation Council for Graduate Medical
      Education competencies and internal medicine Milestones and could be a replicable
      model for internal medicine residency programs that seek to provide community
      health training.

PMID- 24455023
TI  - Development of an ambulatory geriatrics knowledge examination for internal
      medicine residents.
AB  - BACKGROUND: The number of older adults needing primary care exceeds the capacity
      of trained geriatricians to accommodate them. All physicians should have basic
      knowledge of optimal outpatient care of older adults to enhance the capacity of
      the system to serve this patient group. To date, there is no knowledge-assessment
      tool that focuses specifically on geriatric ambulatory care. OBJECTIVE: We
      developed an examination to assess internal medicine residents' knowledge of
      ambulatory geriatrics. METHODS: A consensus panel developed a 30-question
      examination based on topics in the American Board of Internal Medicine (ABIM)
      Certification Examination Blueprint, the ABIM in-training examinations, and the
      American Geriatrics Society Goals and Objectives. Questions were reviewed,
      edited, and then administered to medical students, internal medicine residents,
      primary care providers, and geriatricians. RESULTS: Ninety-eight individuals (20
      fourth-year medical students, 57 internal medicine residents, 11 primary care
      faculty members, and 10 geriatrics fellowship-trained physicians) took the
      examination. Based on psychometric analysis of the results, 5 questions were
      deleted because of poor discriminatory power. The Cronbach alpha coefficient of
      the remaining 25 questions was 0.48; however, assessment of interitem consistency
      may not be an appropriate measure, given the variety of clinical topics on which
      questions were based. Scores increased with higher levels of training in
      geriatrics (P < .001). CONCLUSION: Our preliminary study suggests that the
      examination we developed is a reasonably valid method to assess knowledge of
      ambulatory geriatric care and may be useful in assessing residents.

PMID- 24455024
TI  - Getting out of silos: an innovative transitional care curriculum for internal
      medicine residents through experiential interdisciplinary learning.
AB  - BACKGROUND: Care transitions are common and highly vulnerable times during
      illness. Physicians need better training to improve care transitions. Existing
      transitional care curricula infrequently involve settings outside of the hospital
      or other health care disciplines. INTERVENTION: We created a curriculum to teach
      internal medicine residents how to provide better transitional care at hospital
      discharge through experiential, interdisciplinary learning in different care
      settings outside of the acute hospital, and we engaged other health care
      disciplines frequently involved in care transitions. SETTING/PARTICIPANTS:
      Nineteen postgraduate year-1 internal medicine trainees at an academic medical
      center in an urban location completed experiences in a postacute care facility,
      home health care, and outpatient clinics. PROGRAM DESCRIPTION: The 2-week
      required curriculum involved teachers from geriatric medicine; physical,
      occupational, and speech therapy; and home health care, with both didactic and
      experiential components and self-reflective exercises. PROGRAM EVALUATION: The
      curriculum was highly rated (6.86 on a 9-point scale) and was associated with a
      significant increase in the rating of the overall quality of transitional care
      education (from 4.09 on a 5-point scale in 2011 to 4.53 in 2012) on the annual
      residency program survey. Learners reported improved knowledge in key curricular
      areas and that they would change practice as a result of the curriculum.
      CONCLUSIONS: Our transitional care curriculum for internal medicine residents
      provides exposure to care settings and health care disciplines that patients
      frequently encounter. The curriculum has shown positive, short-term effects on
      learners' perceived knowledge and behavior.

PMID- 24455025
TI  - A memorial service to provide reflection on patient death during residency.
AB  - BACKGROUND: Patient death can be emotionally and psychologically stressful for
      clinicians, particularly clinicians in training. OBJECTIVE: We describe an annual
      memorial service as a novel approach to help internal medicine residents cope
      with and reflect on the experiences of patient death. METHODS: We created a
      memorial service in 2010 for patients who had died under the care of the internal
      medicine residents in our institution. Residents, medical students, and medicine
      faculty attended the 1-hour service. The memorial service was repeated in 2011,
      and a 10-question survey was sent to evaluate its impact. RESULTS: Twenty-two
      participants in either the 2010 or 2011 memorial service responded to the survey.
      Most of the respondents thought that reflection on patient death was important
      (95%) and that the memorial service was helpful in facilitating such reflection
      and bringing closure (95%). CONCLUSIONS: An annual memorial service helps
      trainees cope with the emotional impact of patient death. It can be easily
      adopted by other residency programs. The long-term impact of this experience on
      trainees' well-being and professional development is unknown.

PMID- 24455026
TI  - Building capacity for quality: a pilot co-learning curriculum in quality
      improvement for faculty and resident learners.
AB  - BACKGROUND: Despite a mandate to teach quality improvement (QI) to residents,
      many training programs lack faculty capacity to deliver a QI curriculum.
      OBJECTIVE: We piloted a co-learning curriculum in QI to train residents while
      simultaneously developing QI teachers. We evaluated the curriculum's
      acceptability and feasibility and its effect on faculty engagement in doing and
      teaching QI. METHODS: The curriculum involved 2 half-day, interactive sessions, a
      team-based QI project, and end-of-year project presentations. Key curriculum
      design principles included (1) residents and faculty co-attend all interactive
      sessions, (2) residents and faculty work together on team-based QI projects, and
      (3) QI projects align with divisional QI priorities. Using the Kirkpatrick
      framework for learner outcomes, we focused our program evaluation on Level 1
      (satisfaction) and Level 2 (knowledge and skills acquisition) outcomes using year
      end curriculum evaluations. RESULTS: Our study included 14 residents (70%) and 6
      faculty members (30%). With respect to satisfaction (Kirkpatrick Level 1
      outcome), 93% (13 of 14) of residents and 100% (6 of 6) of faculty participants
      rated the overall curriculum as "above average" or "outstanding." Regarding
      faculty knowledge and skills acquisition (Kirkpatrick Level 2 outcomes), faculty
      self-rated their QI knowledge and interest in QI higher than their intent to
      incorporate QI into future practice and their comfort in teaching or supervising
      QI projects. All 5 faculty respondents (100%) rated the co-learning model for
      faculty development in QI as "above average" or "outstanding." CONCLUSIONS:
      Teaching QI to residents and faculty as co-learners is feasible and acceptable
      and offers a promising model for programs to teach QI to residents while
      concurrently building faculty capacity.

PMID- 24455027
TI  - First steps: exploring use of a prospective, office-based registry as the
      foundation for quality improvement in cardiology training.
AB  - BACKGROUND: Teaching practice-based learning and improvement and systems-based
      practice are challenging. Cardiology fellows at St John Hospital & Medical Center
      participate in a national registry of outpatient cardiology care. OBJECTIVE: We
      assessed the use of the registry, hypothesizing that it could serve as an
      effective foundation for studying ambulatory care, identifying gaps in care, and
      planning interventions to advance competence in practice-based learning and
      improvement and systems-based practice. METHODS: Starting in 2009, trainees
      prospectively entered data for ambulatory cardiac patients into the PINNACLE
      Registry database where compliance with 28 performance measures was calculated
      and reported quarterly. Fellows met with the program director individually and in
      groups to identify performance gaps and to develop and implement plans for
      quality improvement. Cardiology fellows were surveyed annually to assess this
      process. RESULTS: Through March 2012, the fellows had completed 2400 patient
      visits. Participation was feasible because it was cost neutral, with data form
      completion averaging 5 minutes. It was acceptable, with most fellows describing
      positive effects on practice-based learning and improvement without significant
      detriment to work flow. Performance achievement for drug therapies ranged from
      69% (77 of 111) of the patients with atrial fibrillation receiving
      anticoagulation to 99% (486 of 489) of patients with coronary disease receiving
      lipid-lowering therapy. Gaps in system performance included low levels for
      diabetes screening (5%; 20 of 422) and lipid monitoring (10%; 58 of 573). Initial
      quality improvement projects addressed practice gaps with straightforward
      solutions. Improving system performance was more challenging. CONCLUSIONS: Using
      a registry in cardiology trainees' outpatient practice is feasible, acceptable,
      and valuable. It allows for planning and studying the effects of quality
      improvement projects.

PMID- 24455028
TI  - Monitoring resident progress through mentored portfolios.

PMID- 24455029
TI  - What to do about trust? A source of contradiction in interprofessional
      collaboration.

PMID- 24455030
TI  - The 7 habits of highly effective rounding.

PMID- 24455031
TI  - One Program's Experience With the Use of Skype for SOAP.

PMID- 24455032
TI  - A model for improving scholarly activity for pediatrics residents.

PMID- 24455033
TI  - Nervous excitement.

PMID- 24455034
TI  - Scholarly activity in the next accreditation system: moving from structure and
      process to outcomes.

PMID- 24455035
TI  - Advances in the ACGME Clinical Learning Environment Review (CLER) Program.

PMID- 24455036
TI  - Film and digital periapical radiographs for the measurement of apical root
      shortening.
AB  - OBJECTIVES: The aim of this study was to compare the accuracy and agreement of
      scanned film and digital periapical radiographs for the measurement of apical
      root shortening. STUDY DESIGN: Twenty-four film and digital [phosphor plate
      sensor (PPS)] periapical radiographs were taken using the long-cone paralleling
      technique for six extracted teeth before and after 1mm of apical root trimming.
      All teeth were mounted using a typodont and the radiographs were recorded using a
      film holder and polysiloxane occlusal index for each tooth to ensure
      standardization during the different radiographic exposures. The film radiographs
      were scanned and the tooth length measurements for the scanned film and digital
      (PPS) images were calculated using Image-J-Link 1.4 software
      (http://rebweb.nih.gov/ij/index.html) for the two groups. The accuracy and
      agreement among the tooth length measurements from each group and the true tooth
      length measurements were calculated using intra-class correlation (ICC) tests and
      Bland and Altman plots. RESULTS: A high level of agreement was found between the
      true tooth length measurements and the scanned film measurements (ICC=0.979,
      limit of agreement 0.579 to -0.565) and the digital (PPS) radiograph measurements
      (ICC= 0.979, limit of agreement 0.596 to -0.763). Moreover, a high level of
      agreement was found between the scanned film and digital (PPS) radiographs for
      the measurement of tooth length ICC=0.991, limit of agreement 0.411-0.231.
      CONCLUSION: Film and digital (PPS) periapical radiographs are accurate methods
      for measuring apical root shortening with a high level of agreement. Key
      words:Root shortening, measurement, periapical radiographs, film, digital.

PMID- 24455037
TI  - Prevalence of oral mucosal lesions in psoriatic patients: A controlled study.
AB  - OBJECTIVES: This study aimed to investigate and compare the prevalence of oral
      mucosal lesions in a group of psoriatic patients and healthy subjects, and its
      correlation to multiple clinical parameters. STUDY DESIGN: 100 psoriatic patients
      and 100 closely matched controls underwent clinical oral examination. Oral
      lesions were diagnosed according to the criteria proposed by the World Health
      Organization (WHO). The patients filled the Hospital Anxiety and Depression (HAD)
      questionnaire and the Dermatology Life Quality Index (DLQI). The severity of
      psoriasis was assessed by the Psoriasis Area and Severity Index (PASI).
      Categorical variables were evaluated using Chi-square test or Fisher's exact test
      with overall significance set at p< 0.05. RESULTS: Oral mucosal lesions were
      diagnosed in 43 (43%) psoriatic patients and 17 (17%) control subjects (p=0.000).
      Comparing psoriatic patients to control subjects the prevalence of fissured
      tongue (FT) was 35% vs. 13% (p=0.000); geographic tongue (GT) 17% vs. 9%
      (p=0.09); combination of FT and GT 5% vs. 5% (p=1.00); oral candidosis 3% vs. 0%
      (p=0.81); leukoedema 1% vs. 3% (p=0.62); physiologic melanin pigmentations 4% vs.
      1% (p=0.37) respectively. The clinical type of psoriasis, duration of the
      disease, method of disease management (medicated vs. non-medicated for
      psoriasis), smoking habit, psychological status or the disease severity did not
      influence the prevalence of FT and GT. Psoriatic patients who experienced "very
      large" to "extremely large" adverse effect of psoriasis on their quality of life
      have significantly higher prevalence of GT (p=0.04). CONCLUSIONS: FT is
      significantly more common in psoriatic patients compared to controls; hence
      studies investigating the nature of this relationship are warranted. Oral health
      care providers should be aware of the predisposition of psoriatic patients to
      oral candidosis. Key words:Oral lesions, fissured tongue, geographic tongue,
      leukoedema, oral Candida, candidosis, psoriasis.

PMID- 24455038
TI  - Periodontally accelerated osteogenic orthodontics (PAOO) - a review.
AB  - With an increasing number of adult patients coming to the orthodontic clinic, the
      orthodontic professional is constantly looking for ways to accelerate tooth
      movement. Surgical intervention to affect the alveolar housing and tooth movement
      has been described in various forms for over a hundred years. However, it is the
      spirit of interdisciplinary collaboration in orthodontics has expanded the realm
      of traditional orthodontic tooth movement protocols. Periodontal accelerated
      osteogenic orthodontics (PAOO) is a clinical procedure that combines selective
      alveolar corticotomy, particulate bone grafting, and the application of
      orthodontic forces. This procedure is theoretically based on the bone healing
      pattern known as the regional acceleratory phenomenon (RAP). PAOO results in an
      increase in alveolar bone width, shorter treatment time, increased post treatment
      stability, and decreased amount of apical root resorption. Tooth movement can be
      enhanced and cases completed with increased alveolar volume providing for a more
      intact periodontium, decreased need for extractions, degree of facial remodeling
      and increased bone support for teeth and overlying soft tissues, thereby
      augmenting gingival and facial esthetics.The purpose of this article is to
      describe the history, biology, clinical surgical procedures, indications,
      contraindications and possible complications of the PAOO procedure. Key
      words:Periodontics, corticotomy, osteogenic, orthodontics. 

PMID- 24455039
TI  - Matrix metalloproteinase gene polymorphisms and oral cancer.
AB  - Since oral squamous cell carcinoma (OSCC) is the most prevalent malignant cancer
      in the oral cavity, several researches have been performed to study the role of
      important enzymes in this disease. Among them, the matrix metalloproteinases
      (MMPs) are highlighted, due to the fact that they are proteinases responsible to
      degrade many extra-cellular matrix components, making possible the invasion of
      neoplasic cells. Important tools in cancer prognosis have been utilized aiming to
      correlate high levels of MMPs and OSCC, such as immunohistochemical, zymographic
      and mRNA detection methods. However, these techniques are usually applied after
      cancer detection, characterizing a curative but not a preventive medicine. Trying
      to make interventions before the development of the disease and making possible
      the identification of people at high risk and, analysis of modifications in MMP
      genes has been a chance for modern medicine. Recently, polymorphisms in MMP genes
      have been related to different neoplasias, including OSCC. Despite investigation
      is beginning, MMP gene polymorphisms seems to have a promising future in oral
      cancer research and some of the present results have shown that there are MMP
      polymorphisms related to an increased risk for developing oral cancer. Key
      words:Oral cancer, polymorphism, matrix metalloproteinase. 

PMID- 24455040
TI  - Oral rhabdomyosarcoma: A review.
AB  - Rhabdomyosarcoma (RMS) is a rare malignant soft tissue neoplasm comprised of
      cells derived from the primitive mesen!chyme. About 35% of RMS arises in the head
      and neck, are are classified as parameningeal and non-parameningeal forms. These
      are the most common soft tissue sarcoma of the children, adolescents and young
      adults. Their etiopathogenesis and its molecular relevance have been emphasized.
      The first line of treatment is radical excision and this is usually supplemented
      by radiotherapy. It is believed that adjunct combination chemotherapy may greatly
      improve the prognosis. Inadequately treated tumours grow in an infiltrative
      manner and recur in a high percentage of cases. Bone does not constitute an
      effective barrier to the growth of the tumour and bone invasion is a frequent
      finding in head and neck rhabdomyosarcomas. Key words:Rhabdomyosarcomas,
      botryoid, spindle, alveolar, sarcomas, undifferentiated. 

PMID- 24455041
TI  - The "Toronto prosthesis", an appealing method for restoring patients candidates
      for hybrid overdentures: A case report.
AB  - The implant is a therapeutic resource in constant evolution, and the different
      types of implants and techniques have been increasingly used in cases of both
      fully or partially edentulous patients. In some cases they provide more
      conservative treatment, and in others better stability, retention, and function.
      To achieve a satisfactory result, there are several factors that should be taken
      into account: the type and quality of the bone, bone density, the placement
      location of implants, retrievability of restorations, the patient's motivation,
      and economic issues. Trainees should be aware of the limitations of the
      techniques that can be used for successful prosthetic rehabilitation. This work
      describes the prosthetic rehabilitation of a fully edentulous mandible treated
      with dental implants using the 'Toronto Bridge" technique for restoring both
      function and aesthetics. This type of prosthesis is a screwed-in mesostructure
      with milled abutments for the cementation of single or multiple suprastructures.
      This device could also be named "abutment-hybrid overdenture" The main advantages
      and disadvantages of this protocol are discussed. Key words:Implant-supported
      restorations, dental implants. 

PMID- 24455042
TI  - Chronic idiopathic hyperphosphatasia with unusual dental findings - A case
      report.
AB  - Chronic idiopathic hyperphosphatasia(CIH) or juvenile Paget disease is believed
      to be a distinct disease characterized by an increase in the serum alkaline
      phosphatase, cortical thickening and bowing of the long bones, especially the
      femora. It is a rare autosomal recessive bone disorder, with excessive bone
      resorption and bone formation. Skeletal malformations in the legs may cause
      problems in walking and may eventually result in short stature. The radiographic
      appearances include widening of the diaphyses, vertebral osteoporosis, acetabular
      protrusion, and thickening of the skull vault. Intensive bisphosphonate treatment
      prevented the development of deformity and disability but there is no published
      data on long-term efficacy. Bisphosphonate therapy showed suppression of bone
      turnover, doubling of trabecular thickness with no mineralization defect, and no
      osteopetrosis. We report a female of 21 years, a case of chronic idiopathic
      hyperphosphatasia congenital form, with a history of fracture, short stature and
      malformed teeth. She had a waddling gait, bone deformities, kyphoscoliosis and
      curvature of her limbs. Key words:Hyperphosphatasia, autosomal recessive,
      alkaline phosphatase, short stature, cortical thickening, enamel hypoplasia. 

PMID- 24455043
TI  - Endodontic management of three-rooted maxillary second premolar in a patient with
      bilateral occurrence of three roots in maxillary second premolars.
AB  - The possibility of bilateral maxillary second premolars having three separate
      roots is quite low; however, it must be taken into account in clinical and
      radiographic evaluations during endodontic treatment. A correct clinical and
      radiographic diagnosis based on knowledge of root canal anatomy and critical
      interpretation of radiographs is necessary for a safer and successful endodontic
      treatment of these teeth. Failure of root canal treatment can occur due to missed
      roots/canals and often diagnosed when patient experiences continuous post
      operative pain and discomfort. This case report describes the root canal
      treatment of a three-rooted maxillary second premolar in a patient with bilateral
      occurrence of three roots in maxillary second premolars. Key words:Anatomic
      variations, maxillary second premolar, radiculous. 

PMID- 24455044
TI  - Oral lesions and immune status of HIV infected adults from eastern Nepal.
AB  - OBJECTIVE: To document the prevalence, age and gender distribution of oral
      lesions in HIV infected adults and the influence of highly active antiretroviral
      therapy and correlate them to the immune status of the patients. MATERIALS AND
      METHODS: Oral lesions were diagnosed by a detailed physical examination by
      trained and calibrated examiners according to the case definitions established by
      the Oral HIV/AIDS research alliance. Demographic details, risk behavior patterns
      and oral symptoms and habits were collected by a questionnaire. RESULTS: 81
      patients; 54 men and 27 women aged between 20 - 55 years participated in the
      study. A total of 49 patients; 60.5% had some oral lesion when examined. Oral
      candidiasis (21 %) and oral melanosis (21%) were the most common lesions,
      followed by linear gingival erythema, oral hairy leukoplakia, necrotizing
      ulcerative periodontitis/gingivitis, herpes labialis, parotid gland enlargement
      and reccurent apthous ulcers. Oral hairy leukoplakia was exclusively seen in men
      (p=0.018). All six cases of herpes simplex lesion were seen in non - anti retro
      viral group (p=0.073) while oral candidiasis was commonly noted in the anti retro
      viral group (p=0.073). Lowering CD4 counts had the strongest association with the
      prevalence of oral candidasis (p=0.012), pseudomembranous candidiasis (p=0.014)
      and oral hairy leukoplakia (p= 0.065). CONCLUSION: This study shows a high
      prevalence of oral candidiasis, melanosis, linear gingival erythema and oral
      hairy leukoplakia in the patients. Key words:HIV, AIDS, oral lesions, prevalence.

PMID- 24455045
TI  - Odontogenic tumours: A review of 266 cases.
AB  - OBJECTIVES: The aim of this study was to examine the relative frequency of
      odontogenic tumours at a tertiary hospital in Ibadan, as well as to study the
      various histologic types based on WHO 2005 classification and to compare results
      from this study with those of previous studies. STUDY DESIGN: The records of the
      Oral Pathology Department of University College Hospital were reviewed. Lesions
      diagnosed as odontogenic tumours were categorized into four groups based on WHO
      2005 classification and were analyzed for age, sex and site using SPSS for Window
      (version 18.0; SPSS Inc. Chicago, IL) and frequency tables were generated.
      RESULTS: Two hundred and sixty six (41.7%) cases of odontogenic tumours were
      seen. The mean age of occurrence was 32.6 (+/-15.815) years (range3-82 years) and
      peak age was in the third decade of life. Eleven (4.1%) malignant odontogenic
      tumours were seen. Ameloblastoma with 65.4% of cases was the most common
      odontogenic tumour followed by fibromyxoma (14.7%), no case of odontoma was seen
      in this series. CONCLUSION: The findings were mostly similar to those of African
      and Asian series and showed variations from reports from the Americas. The reason
      for the disparity in African and American series needs further investigations.
      Key words:Odontogenic tumour, classification, Nigeria.

PMID- 24455046
TI  - A clinical study of the effect of calcium sodium phosphosilicate on dentin
      hypersensitivity.
AB  - OBJECTIVE: Dentinal hypersensitivity is a commonly encountered problem with
      varied treatment options for its management. A large number of home use products
      have been tested and used for the management of dentinal hypersensitivity. This 8
      week clinical trial investigates the temporal efficacy of commercially available
      calcium sodium phosphosilicate containing toothpaste in comparison to a potassium
      nitrate containing toothpaste. METHODS: A total 20 subjects between the ages of
      18 to 65 years were screened for a visual analogue score (VAS) for sensitivity of
      5 or more by testing with a cold stimulus and randomly divided into test and
      positive control groups. Baseline sensitivity VAS scores to air evaporative
      stimulus were recorded for minimum two teeth. The subjects were prescribed
      respective dentifrices and revaluated for sensitivity scores at 2, 4 and 8 weeks.
      RESULTS: The study demonstrated reduction in symptoms for all treatment groups
      from baseline to 2, 4 and 8 weeks. The calcium sodium phosphosilicate group
      showed a higher degree of effectiveness at reducing hypersensitivity to air
      evaporative stimulus at 2 weeks, than commercially available potassium nitrate.
      However, there was no significant difference in scores of subjects using the
      calcium sodium phosphosilicate toothpaste as compared to potassium nitrate at 4
      weeks and 8 weeks. CONCLUSION: Calcium sodium phosphosilicate showed greater
      reduction in sensitivity compared to potassium nitrate at an earlier stage which
      is of high clinical value. However, based on the findings of the present study
      long term effects of calcium sodium phosphosilicate seem to be less promising
      than previously claimed. Key words:Dentinal desensitizing agents, dentinal
      hypersensitivity, toothpaste, pain measurement.

PMID- 24455047
TI  - Histologic and histomorphometric assessment of eggshell-derived bone graft
      substitutes on bone healing in rats.
AB  - OBJECTIVE: The objective of this study was to histologically and
      histomorphometrically evaluate the efficacy of the new formulations of eggshell
      derived calcium carbonate in rats. STUDY DESIGN: The study was conducted on 30
      adult male rats. Four standardized and circular intrabony defects were created in
      the both maxilla and mandibula of each animal. Three different graft materials
      were prepared as follows: 1) Material A: Eggshell-derived calcium carbonate
      combined with carrageenan gel, 2) Material B: Eggshell-derived calcium carbonate
      combined with xanthan gum gel, and 3) Material C: Eggshell-derived calcium
      carbonate powder. The right mandibular defect sites were grafted with Material A
      in all animals, and defects on the left were grafted with Material B. Defects on
      the right side of maxilla were received Material C in all animals, and all left
      maxillary defects were remained untreated as controls. The animals were
      sacrificed either postoperatively on the 15th day, postoperatively on the 30th
      day or postoperatively on the 45th day. Histomorphometric measurements were made
      of the areas of newly formed bone, necrotic bone, fibrous tissue and residual
      graft material. RESULTS: Material A exhibited the highest level of osteoid
      formation followed by Material B and Material C on the 45th day. In terms of
      osteoid formation, statistically significant differences were observed between
      graft materials and controls at 45th day compared to 15th and 30th day (p<0.05).
      CONCLUSIONS: Eggshell-derived graft substitutes in both gel and powder forms are
      biocompatible materials which may have the potential to enhance the new bone
      formation. Key words:Bone graft material, bone defects, eggshell,
      histopathological evaluation, rat.

PMID- 24455048
TI  - Prevalence of elongation and calcification patterns of elongated styloid process
      in south India.
AB  - OBJECTIVE: Very few studies have been reported in the literature classifying the
      elongation and calcification patterns of styloid process. The present study was
      done to investigate the prevalence of elongation and calcification patterns of
      styloid process in patients attending a dental institution in south India. STUDY
      DESIGN: 600 digital panoramic radiographs of patients with dental problems were
      obtained from the outpatient department of the Dental institution. The apparent
      length of the styloid process was measured by a single experienced oral
      radiologist, with the help of the measuring tools on the accompanying software.
      The type of elongation and calcification patterns of each elongated styloid
      process was classified as per Langlai's classification with few modifications.
      Finally the data was subjected to statistical analysis. RESULTS: Out of 520
      measurable styloid processes (260 panoramic radiographs), 154 styloid processes
      had length greater than 3cm. The mean average length of elongated styloid process
      was 3.67+/-0.62 cm. No significant association was obtained between age and
      length of styloid process. In present study, the type of elongation pattern has
      no effect on the calcification pattern. Our results suggested that Type I
      elongated styloid processes were most likely to be completely calcified (type D),
      but statistically not significant. CONCLUSION: Type I pattern of elongation was
      found to be more prevalent in elder age group and was completely calcified in
      most of the cases. Interestingly, only three patients (out of 260) showed
      symptomatic elongation of styloid process. A relatively high prevalence of type
      IV elongation pattern (9 /154) was obtained in the present study, when compared
      to type III styloid process. Further large scale imaging studies are required to
      evaluate the presence of type IV elongation pattern in various population groups.
      Key words:Eagle's syndrome, Elongated styloid process, Stylopharyngeous muscle,
      Tonsillectomy.

PMID- 24455049
TI  - The influence of different types of fixed orthodontic appliance on the growth and
      adherence of microorganisms (in vitro study).
AB  - Orthodontic appliances serve as different impact zones and modify microbial
      adherence and colonization, acting as foreign reserves and possible sources of
      infection. This study was conducted to investigate the effect of different types
      of fixed orthodontic appliances on the growth and adherence of microorganisms in
      oral flora which are Streptococcus mutans (S. mutans) and Candida albicans. Sixty
      four of four different fixed orthodontic appliance-samples were used, divided
      into four groups of sixteen. Type I: Sapphire brackets- Coated wires, type II:
      Sapphire brackets- Stainless steel wires, type III: Stainless steel brackets-
      Coated wires and type IV: Stainless steel brackets- Stainless steel wires. Oral
      strains of S. mutans and Candida albicans were studied in the present study using
      biochemical test then microbial suspensions were prepared to do the tests of each
      microorganism including the antimicrobial effects of different appliance-samples
      on the growth of microorganisms and their adhesion tests. The results showed
      significant differences between the different appliances in terms of inhibition
      zone formation (P<0.001). The adhesion test, which is classified into low, medium
      and high, showed the adhesion of S. mutans, is low with type I and II, medium
      with type III and high with type IV, whereas the adhesion of Candida albicans is
      medium with both type I and II and high with both type III and IV with high
      significant differences (P<0.001). Appliance with high esthetic appearance,
      sapphire brackets and coated arch wire, showed the least adherence of S. mutans
      and Candida albicans in comparison to other appliances with less esthetic and
      more metal components. Key words:Orthodontic appliance, Adherence, Streptococcus
      mutans, Candida albicans. 

PMID- 24455050
TI  - Appraisal of jaw swellings in a Nigerian tertiary healthcare facility.
AB  - INTRODUCTION: The mandible and maxilla can be the site of myriads of lesions that
      may be categorized as neoplastic, cystic, reactive and infective or inflammatory.
      Literature reviewing jaw swellings in an amalgamated fashion are uncommon,
      probably because aetiologies for these swellings are varied. However, to
      appreciate their relative relationship, it is essential to evaluate the clinico
      pathologic profile of jaw swellings. The aim of this appraisal is to describe the
      array of jaw swellings seen at our hospital from 1990 to 2011, to serve as a
      reference database. MATERIAL AND METHODS: Biopsy records of all histologically
      diagnosed cases of jaw swellings seen at the department of Oral Pathology,
      University College Hospital between January 1990 and December 2011 were
      retrieved, coded and inputted into SPSS version 20. Data on prevalence, age, sex,
      site and histological diagnosis were analysed descriptively for each category of
      jaw swellings. All patients below 16 years were regarded as children. RESULTS: A
      total of 638 jaw swellings were recorded in the 22-year study period. The Non
      Odontogenic Tumours (NOT) were the commonest, accounting for 46.2% of all jaw
      swellings. Odontogenic Tumours (OT) formed 45% of all adult jaw swelling while it
      formed 25.2% in children and adolescents. Ameloblastoma was the commonest while
      the most common NOT was ossifying fibroma (OF). Chronic osteomyelitis of the jaws
      was about 6 times commoner in adult females than males and mostly involved the
      mandible. The most common malignant jaw swelling was Burkitts' lymphoma (BL) that
      was about 7 times more in children than adults. Osteogenic sarcoma was the most
      common malignancy in adults. CONCLUSION: Jaw swellings are extensively varied in
      types and pattern of occurrence. This study has categorized jaw swellings in a
      simple but comprehensive fashion to allow for easy referencing in local and
      international data acquisition and epidemiological comparison. Key words:Jaw
      swellings, odontogenic, Nigeria.

PMID- 24455051
TI  - History of materials used for recording static and dynamic occlusal contact
      marks: a literature review.
AB  - In the discipline of prosthetic dentistry it is important not only to examine the
      occlusion, but to be able to record, store, and transfer the information. Over
      the years many occlusion testing materials have been used. It has been suggested
      the clinical recording and transfer of information using waxes and other
      occlusion recording materials have disadvantages relating to inaccuracy and
      problems of manipulation. Therefore, there has been introduction of many new
      systems for recording occlusion contacts to overcome such problems. The correct
      physiological recovery of occlusion posses as much a challenge as ever for every
      dentist and technician. Even the smallest high spots measuring just a few microns
      can cause dysfunctions like temporo-mandibular pain. Occlusal proportions are
      being constantly changed with every procedure. Therefore, an understanding of the
      synergy of the teeth in static and dynamic occlusion forms the basis of good
      dentistry. The purpose of this review article is to give and overview of the
      various materials and methods that have been used to record occlusal contact
      marks. Key words:Occlusal contact marks, Occlusion indicators, Occlusion test
      materials, Occlusion recording materials. 

PMID- 24455052
TI  - Unicystic ameloblastoma in 3 year old paediatric patient - A rare entity.
AB  - Unicystic ameloblastoma (UA) is a benign epithelial odontogenic tumor of the jaws
      that commonly occurs in 2nd and 3rd decade of life. In fact, this entity is rare
      in children under 12 years of age. It is characterised as a distinct variant of
      ameloblastoma, exhibiting a less aggressive behaviour and a lower rate of
      recurrence than solid conventional ameloblastoma. There are very few reported
      cases of UA occurring in children below five years of age. The purpose of this
      case report is to describe a case of UA involving the crown of an unerupted
      maxillary second premolar in a 3 year old girl. The pathogenesis, clinical
      appearance, radiographic presentation, histological findings and management of
      the tumour have also been discussed. 

PMID- 24455053
TI  - Florid cemento-osseous dysplasia: Report of a case documented with clinical,
      radiographic, biochemical and histological findings.
AB  - Florid cemento-osseous dysplasia (FCOD) has been described as a condition that
      characteristically affects the jaws of middle-aged black women. This condition
      has also been classified as gigantiform cementoma, chronic sclerosing
      osteomyelitis, sclerosing osteitis, multiple estenosis and sclerotic cemental
      masses. It usually exhibits as multiple radiopaque cementum-like masses
      distributed throughout the jaws. Radiographically, FCOD appears as dense,
      lobulated masses, often symmetrically located in various regions of the jaws.
      Computed tomography, because of its ability to give axial, sagittal, and frontal
      views, is useful in the evaluation of these lesions. This article reports the
      case of a 45-year-old white man who was diagnosed with FCOD on the basis of
      clinical, radiographic, biochemical and histological findings. It is of major
      importance to realize that all dentists have a unique opportunity as well as
      ethical obligation to assist in the struggle against wrong dental treatments that
      might save patients dental health. This case report illustrates the point that
      periapical radiolucencies may represent benign fibro-osseous lesions that may be
      overlooked or result in unnecessary endodontic treatment. Key words:Florid
      cemento-osseous dysplasia, florid osseous dysplasia, fibro-osseous lesions. 

PMID- 24455054
TI  - Ancient Schwannoma of the hard palate. An uncommon case report and review.
AB  - Schwannoma or neurilemmoma is an infrequent benign tumor in the oral cavity that
      originates from the Schwann cells on the neural sheath of the peripheral nerves.
      Schwannomas are frequently located in the soft tissues of head and neck region,
      but only a 1 to 12% of them are located in the oral cavity. Some histological
      variants of schwannoma have been described including the cellular, plexiform,
      epithelioid, ancient, and melanocytic types. The "ancient schwannoma" is an
      uncommon variant of this tumor that shows specific histological characteristics,
      and is rare in the oral cavity with less than 15 cases described on the
      literature. Most of them were located in the tongue or in the floor of the mouth,
      being the hard palate an extremely rare localization. We present a new clinical
      case of an ancient schwannoma with a long time of evolution, arising from the
      nasopalatine nerve, and located in the hard palate of a 35 year old female. We
      also review the main clinical and histological characteristics of this pathology.
      Key words:Ancient schwannoma, neurilemmoma, palate, schwannoma. 

PMID- 24455055
TI  - Oral findings in postmenopausal women attending dental hospital in Western part
      of India.
AB  - OBJECTIVES: To know the nature, incidence and severity of oral manifestations
      occurring in postmenopausal women. STUDY DESIGN: Oral changes were observed in
      365 postmenopausal women and 365 age matched male individuals attending the
      department of Oral Medicine and Radiology. The patients were asked about
      complaints of dry mouth, taste and breath changes, mucosal and facial pain and
      were examined for oral changes such as ulceration, white and red lesions. The
      results obtained from the study were then correlated with various other similar
      studies. RESULTS: The important oral findings in postmenopausal women were
      mucosal burning/pain (25.8%), dry mouth (27.1%), altered taste (3.6%), altered
      breath (6.3%) and facial pain (3.6%). Oral submucous fibrosis (OSMF) was
      significantly more common in males (5.5%) as compared to postmenopausal females
      (1.9%). CONCLUSION: Results from the present study reveal that oral symptoms are
      common problems in postmenopausal women. Postmenopausal patients showed
      significantly more oral changes than the control. These changes could be related
      to the hormone alterations. Therefore, dentists need to refer postmenopausal
      women with oral symptoms to a gynaecologist for more careful examinations and
      medical interventions if necessary. Key words:Menopause; postmenopause;
      xerostomia; pallor; oral changes.

PMID- 24455056
TI  - Effectiveness of dental bleaching in depth after using different bleaching
      agents.
AB  - OBJECTIVES: This study evaluated the effectiveness of low- and high-concentration
      bleaching agents on enamel and deep dentin. STUDY DESIGN: Stained bovine incisors
      fragments were randomized placed into 10 groups (n=5), according to the sample
      thicknesses (2.0 mm or 3.5 mm) and bleaching agent: 10% carbamide peroxide (CP)
      (4 h a day/21 days); 6% hydrogen peroxide (HP) with calcium (1:30 h a day/21
      days); HP 20% with calcium (50 min a day/3 sessions with a 7-day interval); HP
      35% (3 x 15 min a day/3 sessions with a 7-day interval); HP 35% with calcium (40
      min a day/3 sessions with a 7-day interval). The samples were stored in
      artificial saliva during the experiment. The color change was evaluated using a
      spectrophotometer at the initial analysis, after artificially staining with black
      tea and after each of the bleaching weeks, and data was expressed in CIE Lab
      System values. The L* coordinate data was submitted to analysis of variance and
      Tukey-Kramer test and the ?E values data was submitted for analysis of variance
      in a split-plot ANOVA and Tukey's test (?=0.05). RESULTS: None of the bleaching
      agents tested differed from the reflectance values on the enamel surface. For
      deep dentin HP 20% and HP 35%, both with calcium, showed the lowest reflectance
      values, which differed from CP 10%. CONCLUSION: It is concluded that high
      concentration hydrogen peroxide with calcium was less effective in deep dentin
      than 10% carbamide peroxide. Key words:Dental bleaching; hydrogen peroxide;
      carbamide peroxide; dental staining.

PMID- 24455057
TI  - Kohlschutter-Tonz Syndrome - Report of an additional case.
AB  - Kohlschutter-Tonz Syndrome is a rare disorder clinically characterized by
      amelogenesis imperfecta, epilepsy and progressive mental deterioration. We
      present an additional case of this syndrome of a nine year-old boy who was
      referred by pigmented teeth. The mental deterioration was associated with speech
      delay, impulsive behavior, attention-deficit/hyperactivity disorder, and learning
      problems. The physical examination revealed a reduction of lower third, slightly
      palpebral fissures, low ear and hair implantation, coarse hair and
      hypertrichosis. The intraoral examination showed alteration in teeth pigmentation
      diagnosed as amelogenesis imperfecta. Although rare, the present case report
      illustrates a syndrome that has dental anomalies and systemic alterations. It is
      important to recognize this syndrome as early as possible and paediatric dentist
      may contribute to the diagnosis and consequently to better manage the patients.
      Key words:Kohlschutter-Tonz syndrome, amelogenesis imperfecta, seizures, mental
      deterioration. 

PMID- 24455058
TI  - Inverted ductal papilloma of the oral cavity secondary to lower lip trauma. A
      case report and literature review.
AB  - Inverted ductal papilloma of the oral cavity is an infrequent benign neoplasm of
      papillary appearance that originates in the secretory duct of a salivary gland.
      The etiology is unknown, though some authors have related it to human
      papillomavirus (HPV) infection. We present the case of a 40-year-old woman with a
      tumor of the lower lip mucosa. Histopathological study of the lesion diagnosed
      inverted ductal papilloma of the oral cavity. Human papillomavirus DNA detection
      and typing based on tumor lesion DNA amplification and posterior hybridization,
      revealed no presence of viral DNA. The antecedents of trauma reported by the
      patient could have played an important role in the development of this tumor. Key
      words:Inverted ductal papilloma, intraductal papilloma, oral papilloma, papillary
      epidermoid adenoma. 

PMID- 24455059
TI  - Comparative split-mouth study of the anesthetic efficacy of 4% articaine versus
      0.5% bupivacaine in impacted mandibular third molar extraction.
AB  - OBJECTIVE: The purpose of this study was to compare the clinical efficacy of
      articaine at 4% (epinephrine 1:100,000) with bupivacaine at 0.5% (epinephrine
      1:200,000) for surgical extraction of impacted mandibular third molars. STUDY
      DESIGN: This was a randomized, double blind, split-mouth, clinical trial. Thirty
      six patients took part and underwent extraction of 72 lower third molars. The
      variables studied were: anesthetic latency time, intra-operative bleeding,
      anesthetic quality, hemodynamic changes during the surgical intervention,
      anesthetic duration in the soft tissues, post-operative analgesia and post
      operative pain at 2, 6, 12 and 24 hours using a visual analogue scale, as well as
      any need for additional rescue medication. RESULTS: Latency time was 2.0 minutes
      for articaine and 3.1 minutes for bupivacaine, with statistically significant
      difference (p<0.05). Bleeding was greater when bupivacaine was used (p<0.05) and
      anesthetic quality was greater with articaine (p<0.05). The duration of soft
      tissue anesthesia was longer with bupivacaine (p<0.05). Differences in post
      operative analgesia, haemodynamic changes, post-operative pain and the quantity
      of rescue medication consumed were not statistically significant (p>0.05).
      CONCLUSIONS: Articaine showed greater clinical efficacy than bupivacaine,
      reducing latency time, bleeding, anesthetic duration in the soft tissues and
      achieving higher anesthetic quality, requiring less reinforcement during surgery
      than bupivacaine. Key words:Articaine, bupivacaine, anesthetic efficacy, impacted
      mandibular third molar.

PMID- 24455060
TI  - Factors influencing caries status and treatment needs among pregnant women
      attending a maternity hospital in Udaipur city, India.
AB  - OBJECTIVES: To estimate the prevalence and severity of dental caries along with
      the treatment needs; to determine the factors that influence dental caries status
      among pregnant women attending a district maternity hospital in Udaipur, India.
      STUDY DESIGN: Study sample comprised of 206 pregnant women attending a district
      maternity hospital in Udaipur, India. Clinical data were collected on dental
      caries by DMFT and treatment needs as described in World Health Organization
      Dentition status and Treatment needs. RESULTS: The overall caries prevalence was
      87%. Mean caries experience differed significantly among women in various
      trimesters, it was found to be 3.59 and 3.00 in 1st and 2nd trimester subjects
      respectively while it was greatest (4.13) among those in 3rd trimester. One
      surface filling was the most predominant treatment need. Age and occupation of
      husband explained a variance of 6.8% and 4.2% for decayed and filled components
      respectively while the only predictor for missing teeth and DMFT that explained a
      variance of 9.6% and 5.7% respectively was trimester of pregnancy. CONCLUSIONS:
      Dental caries experience and the need for one surface restoration increased with
      age. Trimester of pregnancy was a significant predictor for missing teeth and
      DMFT, while decayed teeth and filled teeth were influenced by age and socio
      economic level respectively. Key words:Dental caries, treatment needs, pregnant,
      age, trimester.

PMID- 24455061
TI  - Platform switching on wide-diameter external hex implants: a finite element
      analysis.
AB  - OBJECTIVES: The objective of this work was to use finite element analysis to
      compare the effect of forces coming to bear on abutments 4.1 or 5.0 mm in
      diameter connected to a 5.0 mm implant (i.e. with or without platform switching).
      STUDY DESIGN: A 3D CAD model of a 5 x 11.5 mm external hex implant was developed,
      complete with a connection screw and either of two abutments, one 4.1 and the
      other 5 mm in diameter, to assess the influence of two loading conditions, i.e.
      200 N loaded either axially or off center on the top of the abutment. RESULTS AND
      CONCLUSIONS: In the symmetrically loaded models, greater stresses were
      transmitted to the bone in the area below the neck of the implant in the case of
      the wider-diameter abutment. When the narrower abutment was considered, the
      stress lines remained confined to the metal and were transferred to the bone in a
      more distal position. When the stresses in the bone where compared under non
      symmetrical loading of the larger- and smaller-diameter abutments, the stresses
      reached lower values in the latter case. These findings indicate that platform
      switching (i.e. coupling a 4.1 mm abutment with a 5 mm implant) achieves a
      better, more even distribution of the peri-implant stresses deriving from
      simulated occlusal loads on the bone margins. Key words:Platform switching,
      finite element analysis, implant.

PMID- 24455062
TI  - The efficacy of an experimental single solution versus alternate use of multiple
      irrigants on root dentin microhardness.
AB  - OBJECTIVES: This study was carried-out to evaluate and compare the efficacy of
      various irrigants when used singly or in combination on the microhardness of root
      canal dentin. STUDY DESIGN: A total of 50 root-halves were randomly divided into
      5 groups immediately after the initial baseline microhardness measurements and
      treated with: Group-1; 7.5%Ethylenediaminetetraaceticacid (EDTA) + 2.5%sodium
      hypochlorite (NaOCl), Group-2; 7.5%ethyleneglycol-bis[b-aminoethylether]
      N,N,N0,N0-tetraaceticacid (EGTA) + 2.5%NaOCl, Group-3;
      7.5%trans1,2diaminocyclohexane NNN',N'tetraaceticacid (CDTA) + 2.5% NaOCl, Group
      4; 7.5%EDTA + 2.5% Ethylenediamine (EDA), and Group-5; 1/1 (v/v) EDTA-EDA mixture
      + 1/1 (v/v) EDTA-EDA mixture. Fifty mL of each solution was used for 1 minute.
      The reference and post-treatment microhardness values were measured with a
      Vickers indenter under 80-gram load, 15-second dwell time. Data were analyzed by
      two-way ANOVA and Bonferroni tests (p=0.05). RESULTS: All solutions decreased
      microhardness of dentin (p< 0.05). There was statistically significant difference
      between each group, except Group-1 and 4, after 1st solution application. While
      Group-2 resulted in a greater reduction of dentin hardness, Group-5 caused the
      least change in microhardness values, after 1st solution application (p< 0.05).
      No statistical difference was observed between Groups 1-4, after 2nd solution
      application. However, Group-5 showed a significant difference compared with all
      other groups, after 2nd solution application (p< 0.05). CONCLUSIONS: Under the
      experimental conditions, all tested solutions reduced the microhardness of the
      root canal dentin. EGTA was the most efficient chelating agent. EDTA-EDA single
      mixture has led to least change on the microhardness of root dentin. Key
      words:Microhardness, CDTA, EDTA, EGTA, Ethylenediamine.

PMID- 24455063
TI  - Prevalence of recurrent aphthous ulceration experience in patients attending
      Piramird dental speciality in Sulaimani City.
AB  - OBJECTIVE: The aim of this study is to report the prevalence and risk factors of
      recurrent aphthous ulceration (RAU) in patients attending Piramird dental
      speciality for seeking dental treatment. STUDY DESIGN: A cross-sectional survey
      was carried out among patients (n=1100) who were visiting the department of oral
      medicine at Piramird dental speciality center in Sulaimani from December 2011
      February 2012. The age range of the patients were between 10-79 years, with mean
      age of (34.27+/-14.14). 446 (44.6%) of participants were males and 554 (55.4%)
      were females, with male/female ratios of 0.80:1. All individuals had to answer
      specific questions including personal data (age, sex), level of education,
      occupation and smoking habit; etc. Additional questions were related to the risk
      factors that might be related to the condition. Chi Square test was used to
      analyze the data. RESULT: The life time prevalence of RAU experience was 28.2%
      (n=282). It was highly significantly more common among females (31.76%)
      (p<0.004). The most commonly affected age group was 20-29 years (36.28%). The
      highest prevalence of RAU experience was seen among mere students (36.8%); Among
      non smokers there were highly significantly more patients with RAU experience
      (30%) than in heavy smoker patients (12.22%), (p=0.000). 34.4% of patients had
      family history of RAU. Lips and buccal mucosae were the commonest sites of
      ulcerations (73.10%), and the major risk factor was stress (43.3%). CONCLUSION:
      This study has provided information about the epidemiologic aspects of recurrent
      aphthous ulceration, Based on the finding of this study, RAU is a common,
      recurrent painful oral ulceration. This study point to the importance of a
      thorough history taking to identify the patient's main risk factors to get
      preventive measures, therefore treatment will be tailored for each patient
      accordingly. And the author concluded that stress was the major risk factor,
      thus, stress-management interventions suggested to be beneficial in reducing RAU
      recurrence episodes. Key words:Recurrent aphthous ulceration, prevalence, stress.

PMID- 24455064
TI  - Effects of simultaneous nicotine and alcohol use in periodontitis progression in
      rats: A histomorphometric study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of alcohol and
      nicotine, when used alone or simultaneously, on the alveolar bone loss area
      resulting from ligature-induced periodontitis in rats. STUDY DESIGN: Forty adult
      male rats received a cotton ligature in the first lower molar sulcular area, and
      the animals were randomly assigned to different treatments (n = 10, each group)
      including daily peritoneal injections of saline solution (group A), submitted to
      self-administration of alcohol 25% (group B), nicotine solution in concentration
      0.19 MUl/ml (group C), and nicotine solution in concentration 0.19 MUl/ml plus
      self-administration of alcohol 25% (group D). Five weeks later, the animals were
      sacrificed, and the samples were routinely processed for semi-serial decalcified
      sections. RESULTS: Ligated teeth showed more alveolar bone loss than unligated
      ones (p < 0.05). Unligated teeth showed no significant differences between each
      other (p > 0.05). Analyses between the ligated teeth showed that the group C
      (nicotine) or group B (alcohol 25%) each had increasing alveolar bone loss in the
      furcation area, and the simultaneous combination alcohol and nicotine (group D)
      intensified these effects (p < 0.05). CONCLUSION: The results suggest that the
      simultaneous combination of alcohol and nicotine have a synergistic effect in the
      progression of periodontitis, evidenced by increased furcation region bone
      destruction in periodontal disease in rats. Key words:Alveolar bone loss,
      periodontitis, nicotine, alcohol, rats.

PMID- 24455065
TI  - The effect of cigarette smoking on the severity of pain, swelling and trismus
      after the surgical extraction of impacted mandibular third molar.
AB  - OBJECTIVE: The study objective was to investigate the effect of cigarette smoking
      on the severity of pain, swelling and trismus on male after the surgical removal
      of impacted lower third molar. MATERIAL AND METHODS: This prospective comparative
      study was conducted for 150 male in two groups of patients, smokers and non
      smokers. Each group consisted of 75 patients; smoking patient were the ones who
      smoke more than twenty cigarettes per day for more than one year of continuous
      smoking. Postoperative pain was evaluated using a visual analog scale (VAS) and
      the degree of swelling was evaluated through facial reference points' variation.
      The presence of trismus was analyzed through measurement of the interincisal
      distance (IID). RESULT: Clinical and radiographic examinations were carried out.
      Data regarding the age, gender, angulations type, depth and width of impactions
      were evaluated and analyzed The severity of pain, swelling and trismus on the
      1st, 2nd , 5th and 7thday postoperatively was estimated. In both groups the pain
      and trismus were reported to be in peak level during the first post-operative day
      while post-operative swelling reaches its peak level in the second postoperative
      day. CONCLUSION: Cigarettes smoking do not have any significant relationship with
      the severity of pain, swelling and trismus after surgical removal of lower third
      molar on male gender. Key words:Cigarettes smoking, pain, swelling, trismus,
      impacted lower third molars.

PMID- 24455066
TI  - Quality of life in patients with dysphagia after radiation and chemotherapy
      treatment for head and neck tumors.
AB  - OBJECTIVE: The aim of this study is to analyze subjectively, using the SWAL-QOL
      questionnaire, swallowing dysfunction and associated factors after treatment with
      radiotherapy and chemotherapy in patients treated for head and neck cancer.
      MATERIAL AND METHODS: This is a cross-sectional study, based on the selection of
      patients with tumors of the head and neck area, treated with radiotherapy with or
      without chemotherapy during the years 2000 to 2006 at the Oncology Institute of
      Juiz de Fora. The data were analyzed using SPSS 15.0 software, and were evaluated
      using the chi-square test to compare differences in proportions between groups.
      The statistical significance level was set at 5%. RESULTS: It was observed that
      with respect to foods of solid consistency, there was a statistically significant
      difference for mouth tumors (p<0.01), with a tendency in this group to use softer
      foods, easier to chew (stews, boiled vegetables, creamy soups, canned fruit).
      With reference to the domains of the SWAL-QOL, the location of the tumor in the
      mouth was statistically associated with the lowest quality of life in the
      symptoms domain (p<0.05). The female gender variable was associated with the
      lowest perceived quality of life in several domains, namely swallowing (p=0.02);
      fatigue (p=0.008); symptoms (p=0.009). Age (split below and above 60 years) was
      not associated with differences in perceived quality of life in any domain.
      CONCLUSION: Tumor in the mouth and the total dose of radiation in the superior
      fossa were associated with the lowest quality of life in the symptoms domain. The
      female gender variable was associated with the lowest perceived quality of life
      in several domains This study shows that speech therapy should maintain a
      presence in the teams, to then guide the rehabilitation of organic dysphonia and
      mechanical dysphagia possibly afflicting patients after cancer treatment with
      radiation therapy and chemotherapy. Key words:Quality of life, dysphagia, head
      and neck neoplasms, rehabilitation.

PMID- 24455067
TI  - Prevalence of tongue lesions in the Indian population.
AB  - OBJECTIVE: Tongue lesions are a health concern for the dental practitioners and
      the patients as they constitute a significant proportion of oral mucosal lesions.
      The aim of the present study was to determine the prevalence of various tongue
      lesions in the Indian population. MATERIAL AND METHODS: 4926 patients attending
      the Department of Oral Medicine and Radiology were examined for the presence of
      various tongue lesions during the period from October, 2010 to September, 2012.
      The age of the patients ranged from 12-80 years with a mean age of 36.51 years.
      RESULTS: The prevalence of tongue lesions was 12.07%. The most common lesion
      diagnosed was coated tongue affecting 28.0% of the subjects, followed by
      geographic tongue (16.4%), fissured tongue (14.9%) and depapillated tongue
      (11.5%). Males were more frequently affected than females. The most common
      systemic condition observed in the patients with tongue lesions was anaemia
      (189), followed by hypertension (47) and diabetes mellitus (38). CONCLUSION: The
      high prevalence necessitates adequate awareness of the various tongue lesions in
      the general population. The dental clinicians should also be knowledgeable about
      the etiopathogenesis, clinical presentation, diagnosis, and treatment of these
      lesions. Key words:Tongue lesions, prevalence, Indian population, coated tongue.

PMID- 24455068
TI  - Comparing the antibacterial activity of gaseous ozone and chlorhexidine solution
      on a tooth cavity model.
AB  - OBJECTIVE: To evaluate the antibacterial activity of gaseous ozone and
      chlorhexidine solution on a tooth cavity model. STUDY DESIGN: Twenty-one human
      molars were divided into 3 groups. Cavities were then cut into the teeth (4 per
      tooth, 28 cavities per group). After sterilization, the teeth were left in broth
      cultures of 106 colony-forming units (CFU) ml-1 of Streptococcus mutans (S.
      mutans) at 36 degrees C for 48 h. The appropriate treatment followed (group A,
      control; group B, 2% chlorhexidine solution; and group C, 80s of treatment with
      ozone, and the cavities were then filled with composite resin. After 72h, the
      restorations were removed, dentin chips were collected with an excavator, and the
      total number of microorganisms was determined. RESULTS: Both of the treatments
      significantly reduced the number of S. mutans present compared with the control
      group and there was a significant difference between the all groups in terms of
      the amount of the microorganisms grown (p < 0.05). Group B was beter than group
      C; and group C was better than group A. Moreover, it was found that the amount of
      the growth in the group of chlorhexidine was significantly less than that of the
      ozone group (p < 0.05). CONCLUSION: Chlorhexidine solution was the antibacterial
      treatment most efficacious on S. mutans; however, ozone application could be an
      anlternative cavity disinfection method because of ozone's cavity disinfection
      activity. Key words:Antibacterial activity, chlorhexidine, ozone, streptococcus
      mutans, tooth cavity.

PMID- 24455069
TI  - Comparison of the effect of different medicaments on surface reproduction of two
      commercially available Polyvinyl Siloxane impression materials - An Invitro
      Study.
AB  - OBJECTIVE: To determine the effect of different retraction cord medicaments on
      surface detail reproduction of polyvinyl siloxane impression materials and
      compare this effect on any two brands of commercially available polyvinyl
      siloxane impression materials. MATERIAL AND METHODS: Four stainless steel dies
      were made according to ADA specification no.19. Three dies were treated with
      aluminium chloride (5%), ferric sulphate (13.3%) and epinephrine (0.1%) while the
      fourth one was left untreated to serve as control. Two impression materials
      (Dentsply and 3M ESPE) were used. RESULTS: All the three medicaments adversely
      affected the surface detail reproduction of both the brands of the polyvinyl
      siloxane impression materials. These effects were statistically significant as
      compared to untreated control. The impressions of 3M ESPE brand have shown better
      surface detail reproduction as compared to Dentsply impression material.
      CONCLUSION: Surface detail reproduction of the polyvinyl siloxane impression
      materials is adversely affected by the retraction cord medicaments. The presence
      of moisture or any traces of the medicaments should be removed from the tooth
      surface to provide a dry field for the correct reproduction of the surface detail
      of these materials. Key words:Polyvinyl Siloxane, retraction cord medicaments,
      surface detail reproduction.

PMID- 24455070
TI  - A review of oral biopsies in children and adolescents: A clinicopathological
      study of a case series.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinicopathological features
      of oral lesions in children and adolescents diagnosed in an Oral Pathology
      Laboratory. STUDY DESIGN: Between 2000 and 2010, all oral lesions diagnosed in
      patients younger than 18 years old, from the Oral Pathology Laboratory, Federal
      University of Pernambuco, Brazil, were selected for the study. The clinical data
      were obtained from the patient charts filed in the Laboratory. All cases were
      microscopically reviewed and the diagnosis classified into 10 categories.
      RESULTS: From the 2395 lesions, 315 (13.1%) occurred in this age group. The
      lesions were more common in the female gender (59%) during the second decade of
      life (69%). The inflammatory/reactive lesions were the most common (64.4%),
      followed by the epithelial and soft tissue neoplasms (8.6%). The mucocele (33.3%)
      was the most common lesion, with the lip mucosa representing the most affected
      site (48%). In 61.5% there was concordance between clinical hypothesis of
      diagnosis and histopathological diagnosis. CONCLUSIONS: Inflammatory/reactive
      lesions were the most common biopsied lesions and the lip the most frequent site.
      Similar studies are important, reinforced by the low correlation between clinical
      diagnosis and histopathological diagnosis. Key words:Adolescents, children,
      differential diagnosis, oral diseases, prevalence.

PMID- 24455071
TI  - Fibre post behaviour prediction factors. A review of the literature.
AB  - INTRODUCTION: The advantages of fibre posts over stainless steel posts have been
      demonstrated in numerous studies. For clinical success, various factors need to
      be taken into account in post-retained restorations. MATERIAL AND METHODS: A
      review was made of literature on fibre posts published from 2000 to February
      2011, identified through searches of the PubMed/Medline databases. RESULTS: The
      position of the tooth in the arch, ferrule size, proximal contact, periodontal
      support and restoration type are survival prediction factors that should be
      considered when performing post-endodontic restoration. Since fibre posts present
      good biomechanical behaviour as a result of their elastic modulus, which is
      similar to that of dentine, treatment failure occurs through decementation rather
      than because of root fracture, as occurs with metal posts. The shape of the post
      and, consequently, the thickness of the luting, can modify the retention
      capacity. Consequently, more anatomically-shaped posts have been developed, as
      have new techniques to reduce the volume of the dentine/cement interface: lateral
      condensation, surface remodelling or custom designs. CONCLUSIONS: Different
      aspects of the preparation process can be modified to assist in improving fibre
      post retention, but further investigation, mainly clinical, is needed to acquire
      a better understanding of how different factors influence the long-term clinical
      behaviour of the posts. Key words:Fiber post, post shape, post adaptation, post
      retention, endodontics.

PMID- 24455072
TI  - Granular cell ameloblastoma of jaw - Report of a case with an emphasis on its
      characterization.
AB  - Ameloblastoma is a neoplasm of odontogenic epithelium, especially of enamel organ
      type tissue that has not undergone differentiation to the point of hard tissue
      formation. It accounts for approximately 10% of all tumors originating from
      gnathic bones. It exhibits diverse microscopic patterns which occurs either
      singly or in combination with other patterns. Granular cell ameloblastoma is a
      rare condition, accounting for 3.5% of all ameloblastoma cases that shows marked
      transformation in the cytoplasm of tumor cells, which are usually stellate
      reticulum like cells. The transformed cells possess very coarse, granular,
      eosinophilic cytoplasm. The "granular change" is thought to be due to a
      dysfunctional status of neoplastic cells, and the pathogenesis of this tumour
      seems to be age-related. Ultrastructural, histochemical, and immunohitochemical
      studies have revealed that cytoplasmic granularity is caused by overload; however
      the mechanism ivolved remains poorly understood. This article describes a case of
      granular cell variant of ameloblastoma affecting a 55-year old female. Key
      words:Ameloblastoma, granular cell, odontogenic tumor. 

PMID- 24455073
TI  - Influence of low concentration acid treatment on lithium disilicate core/veneer
      ceramic bond strength.
AB  - OBJECTIVE: This study evaluated the influence of low concentration acid treatment
      on the shear bond strength between lithium disilicate (LD) infrastructure and
      veneering porcelain. The surface morphology characteristic after this acid
      treatment was also examined. STUDY DESIGN: LD reinforced ceramic cylinders (n=10)
      (IPS e.max Press, Ivoclar-Vivadent, Schaan, Liechtenstein) were treated (LD
      treated) with a low concentration acid solution (Invex Liquid - Ivoclar-Vivadent,
      Schaan, Liechtenstein) or not treated with the acid solution (LD-untreated). They
      were veneered with a glass ceramic (IPS e.max Ceram, Ivoclar-Vivadent, Schaan,
      Liechtenstein). A metal ceramic group (CoCr) was tested as control. Shear bond
      strength (SBS) was conducted using a universal testing machine at 0.5 mm/min.
      Surface morphology characteristics after acid treatment were analyzed using
      scanning electron microscopy. RESULTS: The acid treatment at low concentrations
      did not influence the SBS of the LD/veneering porcelain interface. The CoCr group
      showed the significant higher SBS value (35.59 +/- 5.97 MPa), followed by LD
      untreated group (27.76 +/- 3.59 MPa) and LD-treated (27.02 +/- 4.79 MPa). The
      fracture modes were predominantly adhesive for CoCr group and cohesive within the
      infrastructure for DL groups. Scanning Electron Microscopy (SEM) analysis showed
      no morphological differences between treated and untreated LD surfaces.
      CONCLUSIONS: Low concentration acid treatment did not improved SBS of veneering
      ceramic to LD and did not cause morphological changes on the LD surface. Key
      words:Lithium disilicate, glass ceramics, acid etching, shear bond strength,
      scanning electron microscopy.

PMID- 24455074
TI  - Influence of surface treatments on enamel susceptibility to staining by cigarette
      smoke.
AB  - OBJECTIVES: The purpose of this study was to evaluate the influence of
      remineralizing agents, including artificial saliva, neutral fluoride, and casein
      phosphopeptide-amorphous calcium phosphate (CPP-ACP), on the susceptibility of
      bleached enamel to staining by cigarette smoke. STUDY DESIGN: Fifty bovine enamel
      blocks were randomly divided into five groups (n = 10): G1- bleaching; G2-
      bleaching and immersion in artificial saliva; G3- bleaching and application of
      CPP-ACP; G4- bleaching and application of neutral fluoride; and G5- untreated
      (Control). Teeth were bleached with 35% hydrogen peroxide and treated with the
      appropriate remineralizing agent. After treatment, all groups were exposed to
      cigarette smoke. Enamel color measurements were performed at three different
      times: before treatment (T1), after treatment (bleaching and remineralizing
      agent) (T2), and after staining (T3), by using the CIE Lab method with a
      spectrophotometer. The data coordinate L* was evaluated by analysis of repeated
      measures PROC MIXED and Tukey-Kramer's test, and the DeltaE values were submitted
      to one-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: The G1 group did not
      show any statistically significant difference for L* values between times T1 and
      T2. The G4 and G5 groups showed lower L* values at T3 compared to T2. No
      significant differences between the groups were observed for DeltaE (after
      treatment and staining). However, G4 showed a clinically apparent color change.
      CONCLUSIONS: Treatment of bleached enamel with neutral fluoride can contribute to
      the increased staining of enamel due to cigarette smoke. Key
      words:Spectrophotometer, remineralizing agents, bleaching.

PMID- 24455075
TI  - The influence of topic and systemic administration of copaiba oil on the alveolar
      wound healing after tooth extraction in rats.
AB  - The Copaiba oil has been used as an auxiliary treatment of inflammations, skin
      disorders and stomach ulcers, however, in dentistry, this "alternative" medicine
      has not been investigated yet. The purpose of this study was to evaluate the
      influence of topic and systemic administration of copaiba oil on the alveolar
      wound healing after tooth extraction. Twenty-eight wistar male rats had their
      lower first molar teeth extracted. Subsequently, they were divided in four
      groups, according to the treatment performed: (a) alveolar socket irrigation with
      copaiba oil; (b) alveolar socket irrigation with physiological serum; (c) daily
      gavage with copaiba oil or (d) daily gavage with physiological serum. After the
      sacrifice, the mandibles were removed and processed in order to obtain
      decalcified histological sections. The results demonstrated high level of
      epithelial migration, small number of inflammatory cells and vascular enhancement
      in the animals which received systemic administration of copaiba oil. The rats
      treated with topic administration of copaiba oil presented ulcerations and large
      number of inflammatory cells. An increased bone neoformation was observed in both
      groups treated with copaiba oil when compared with placebo group. It could be
      concluded that topic or systemic administration of copaiba oil leads to a better
      alveolar bone healing, however the topic application on connective tissue should
      be carefully considered, regarding the whole socket wound healing. Key
      words:Alveolar wound healing, oil-resin, copaiba. 

PMID- 24455076
TI  - Salivary and gingival crevicular fluid histatin in periodontal health and
      disease.
AB  - OBJECTIVES: Histatin, with its anti bacterial, anti protease, and wound closure
      stimulating property might influence the pathogenesis of periodontal disease.
      This study assessed the presence of histatin in gingival crevicular fluid (GCF);
      the levels of salivary and GCF histatin in periodontal disease. MATERIAL AND
      METHODS: It was a cross sectional study that included systemically healthy forty
      five subjects (22 males and 23 females) between the age group of 20 to 45 years.
      Based on Gingival Index (Loe and Silness ,1963) and Russell's Periodontal Index
      they were grouped as 15 healthy (Group 1), 15 gingivitis (Group 2), and 15
      periodontitis (Group 3) subjects. Whole pooled unstimulated saliva was collected
      by asking the patient to spit in a sterile container and GCF samples were
      collected using a micropipette from all the subjects. Histatin levels were
      assessed using Enzyme Linked Immunosorbent Assay (ELISA). The intergroup
      comparison was done by ANOVA and Mann Whitney U Test was done for pair wise
      comparison. RESULTS: The results of this study show that histatin is present in
      saliva and gingival crevicular fluid. When the salivary histatin levels were
      compared it was found that the levels of histatin increase from health to
      periodontitis but the levels of histatin in the gingival crevicular fluid and
      saliva had no correlation with severity of periodontal disease as there was no
      statistically significant difference between the three groups. CONCLUSIONS: It
      can be concluded that histatin cannot be used as a potential marker of
      periodontal disease. Key words:Periodontal disease, histatin, gingival crevicular
      fluid, saliva, gingival index, periodontal index, enzyme linked immunosorbent
      assay.

PMID- 24455077
TI  - Prevalence of taurodontism in the North Indian population.
AB  - OBJECTIVES: Taurodontism affects primarily molars and premolars in both the
      deciduous and permanent dentition. The aim of the study was to assess the
      prevalence of taurodontism in the North Indian population. STUDY DESIGN: 4143
      patients were studied by analyzing the panoramic radiographs for the presence of
      taurodontism which is defined as the presence of an apically displaced pulp
      chamber and the tooth lacks the usual constriction at the cementoenamel junction.
      The age of the patients ranged from 13 to 38 years with a mean age of 21.8 years.
      RESULTS: Taurodontism was found in 17 patients with a prevalence of 0.4% of which
      0.21% were males and 0.19% females. Taurodonts were significantly more common in
      the maxilla (65.6%) than in the mandible (34.4%) (p<0.05) and the maxillary
      second molar (34.4%) was the most commonly involved tooth. According to the
      morphology hypotaurodonts were most common (75%) but there was no significant
      difference in males and females (p>0.05). CONCLUSION: Taurodontism is relatively
      uncommon in the North Indian population. Further large scale studies need to be
      carried out to assess its prevalence in the general population. A family history
      of other anomalies should also be considered for affected patients. Key
      words:Taurodontism, prevalence, maxillary second molar.

PMID- 24455078
TI  - Prevalence of dental anomalies in Indian population.
AB  - OBJECTIVES: Developmental anomalies of the dentition are not infrequently
      observed by the dental practitioner. The aim of the present study was to
      determine the prevalence of dental anomalies in the Indian population. STUDY
      DESIGN: A retrospective study of 4133 panoramic radiographs of patients, who
      attended the Department of Oral Medicine and Radiology, Jodhpur Dental College
      General Hospital between September 2008 to December 2012 was done. The ages of
      the patients ranged from 13 to 38 years with a mean age of 21.8 years. The
      orthopantomographs (OPGs) and dental records were examined for any unusual
      finding such as congenitally missing teeth, impactions, ectopic eruption,
      supernumerary teeth, odontoma, dilacerations, taurodontism, dens in dente,
      germination and fusion, among others. RESULTS: 1519 (36.7%) patients had at least
      one dental anomaly. The congenitally missing teeth 673 (16.3%) had the highest
      prevalence, followed by impacted teeth 641 (15.5%), supernumerary teeth 51 (1.2%)
      and microdontia 41 (1.0%). Other anomalies were found at lower prevalence ranging
      from transposition 7 (0.1%) to ectopic eruption 30 (0.7%). CONCLUSION: The most
      prevalent anomaly in the Indian population was congenitally missing teeth
      (16.3%), and the second frequent anomaly was impacted teeth (15.5%), whereas,
      macrodontia, odontoma and transposition were the least frequent anomalies, with a
      prevalence of 0.2%, 0.2% and 0.1% respectively. While the overall prevalence of
      these anomalies may be low, the early diagnosis is imperative for the patient
      management and treatment planning. Key words:Dental anomaly, prevalence,
      panoramic radiography.

PMID- 24455079
TI  - Toluidine blue staining as an adjunctive tool for early diagnosis of dysplastic
      changes in the oral mucosa.
AB  - Prognosis of oropharyngeal squamous cell carcinoma depends on early diagnosis,
      despite advanced surgical techniques, the 5-year survival rate remains ~40-50%.
      Unfortunately, it is usually detected when it becomes symptomatic. This requires
      treatment which gives rise to a high rate of morbidity and mortality and,
      furthermore, early detection of oro-pharyngeal pre-malignant lesions is important
      to improve the survival rate and quality of life. Since dysplasia and in situ
      carcinoma contain much more DNA and RNA than the normal surrounding epithelium,
      the use of in vivo staining, by means of toluidine blue dye, is based on the fact
      that it is an acidophilic dye that selectively stains acidic tissue components
      such as DNA and RNA. Toluidine blue staining is considered to be sensitive in
      identifying early oro-pharyngeal premalignant and malignant lesions. In the
      present study, the use of toluidine blue staining was taken into consideration to
      identify clinically doubtful oro-pharyngeal lesions and to compare toluidine blue
      stain and with the histological evaluation. Key words:Early detection, improved
      survival, pre-cancer, toluidine blue, vital staining. 

PMID- 24455080
TI  - Intraoral Schwannomas: Presentation of a series of 12 cases.
AB  - INTRODUCTION: Schwannomas are benign and not very frequent tumors of the
      peripheral nerves, derived from the nerve supporting Schwann cells. STUDY DESIGN:
      Data were collected on the clinical manifestations (sex, age), location, size and
      symptonts of the lesions as well as the evolution time and the initial
      (presumption) diagnosis. RESULTS: Twelve patients were documented, with a mean
      age of 29,5 +/- 12,1 years (range 16-50) and a balanced gender distribution. The
      mean duration of the lesions was 42,17+/- 45,3 months. The lesion located in the
      floor of the mouth was the largest tumor, measuring about 4 cm in maximum
      diameter, while the average size of the 12 schwannomas was 2.04+/- 1.1 cm.
      CONCLUSION: We present 12 oral schwannomas diagnosed and treated over a period of
      10 years. Key words:Schwannomas, oral benign tumor, neurilemmoma.

PMID- 24455081
TI  - Effects of recycling and bonding agent application on bond strength of stainless
      steel orthodontic brackets.
AB  - OBJECTIVES: 1) to assess different methods of recycling orthodontic brackets, 2)
      to evaluate Shear Bond Strength (SBS) of (a) new, (b) recycled and (c) repeated
      recycled stainless steel brackets (i) with and (ii) without bracket base primer.
      STUDY DESIGN: A total of 180 extracted human premolar teeth and 180 premolar
      stainless steel brackets were used. One hundred teeth and 100 brackets were
      divided into five groups of 20-teeth each. Four methods of recycling orthodontic
      brackets were used in each of the first four groups while the last one (group V)
      was used as the control. Groups (I-V) were subjected to shear force within half
      an hour until the brackets debond. SBS was measured and the method showing the
      highest SBS was selected. A New group (VI) was recycled twice with the selected
      method. Six subgroups (1-6) were established; the primer was applied for three
      sub-groups, and the composite was applied for all brackets. Brackets were
      subjected to the same shear force, and SBS was measured for all sub-groups.
      RESULTS: There was a significant difference between the mean SBS of the
      sandblasting method and the means of SBS of each of the other three methods.
      There was however, no significant difference between the mean SBS of the new
      bracket and the mean SBS of recycled bracket using sandblasting. The mean SBS of
      all sub-groups were more than that recommended by Reynolds (17) in 1975. Brackets
      with primer showed slightly higher SBS compared to those of brackets without
      bonding agent. CONCLUSION: To decrease cost, sandblasted recycled orthodontic
      brackets can be used as an alternative to new brackets. It is recommended to
      apply a bonding agent on the bracket base to provide greater bond strength. Key
      words:Recycled bracket, shear bond strength, sandblasting, stainless steel
      orthodontic bracket.

PMID- 24455082
TI  - Surgical techniques for smile restoration in patients with Mobius syndrome.
AB  - Mobius syndrome is a congenital condition, the etiology when is not associated
      with misoprostol is not well defined. Signs and symptoms include difficulty
      swallowing, speech problems, drooling, strabismus, limitation of eye movement and
      more importantly, the facial blankness that these individuals have, result of the
      facial paralysis, due to atrophy of the cranial nerves that are involved in this
      condition. The ability to express emotions is affected and are considered
      "children without a smile." There is currently no treatment to solvent the birth
      defects, the treatment options for reduce these alterations is the surgical
      option that has as main objective to restore muscle function through various
      techniques, used as required, the possibilities of applying them, is taking into
      consideration the outcome of the procedure to execute. Among the surgical
      techniques used mainly: the lengthening myoplasty of the temporal muscle,muscle
      transfers, cross-facial grafting, neurorrhaphy and nerve transposition, of which
      latter are the best performers, giving the patient a more natural, in as far as
      regards expression and function. Key words:Mobius syndrome, surgery, smile,
      facial nerve, muscle transfer, transfer nerve, temporalis muscle. 

PMID- 24455083
TI  - Solitary fibrous tumor of the parotid gland: Case report.
AB  - Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that usually
      develops in the pleura and peritoneum. The head and neck region is involved in
      only 6% of the cases. Involvement of the parotid gland is a rare phenomenon, with
      only 24 cases reported in the literature. The aim of this study is to report an
      additional case of SFT affecting the parotid gland, and to review the literature
      on previously reported cases. The patient was a 42-year-old male with a 4-cm,
      fibro-elastic, movable, painless nodule in the inferior lobe of the parotid
      gland. The lesion was surgically excised and, following histopathological and
      immunohistochemical analysis, a diagnosis of SFT was rendered. The patient has
      been followed-up for ten months, with no signs of recurrence. Clinical,
      histopathological, immunohistochemical and treatment aspects of the tumor are
      discussed. Key words:Solitary fibrous tumor, parotid gland, case report. 

PMID- 24455084
TI  - In vitro comparison of flexural strength and elastic modulus of three provisional
      crown materials used in fixed prosthodontics.
AB  - OBJECTIVES: To evaluate and compare the flexural strength and the elastic moduli
      of three provisional crown materials (methyl methacrylate based autopolymerized
      resin, bis acryl composite based autopolymerized resin and urethane
      dimethacrylate based light polymerized resin) after storing in artificial saliva
      and testing at intervals of 24 hours and 7 days. STUDY DESIGN: A metal master
      mould with four slots of dimensions 25x2x2 mm was fabricated to obtain samples of
      standard dimensions. A total of 135 specimens were thus obtained with 45 each of
      three provisional materials. Further 15 samples of each group were tested after
      storing for one hour at room temperature and again at intervals of 24 hours and 7
      days after storing in artificial saliva. Three point flexural tests were carried
      out in the universal testing machine to calculate the flexural strength and the
      elastic modulus. The changes were calculated and data was analyzed with Fisher's
      test and ANOVA. RESULTS: The flexural strength of the methyl methacrylate resin
      reduced significantly while bis-acrylic composite resin showed a significant
      increase in its flexural strength after storing in artificial saliva for 24 hours
      and the values of both remained constant thereafter. Contrary to these findings,
      light polymerized resin showed a significant decrease in flexural strength after
      storing in artificial saliva for 24 hours and then significantly increased in
      flexural strength after 7 days. However the changes in the values for elastic
      modulus of respective materials were statistically insignificant. CONCLUSION:
      Methacrylate based autopolymerizing resin showed the highest flexural strength
      and elastic moduli after fabrication and after storing in artificial saliva and
      for 24 hours and 7 days. Bis-acrylic composite resin showed the least flexural
      strength and elastic moduli. Key words:Provisional restorations, interim
      restorations, Methyl Methacrylate, composite restoration, flexural strength,
      elastic moduli.

PMID- 24455085
TI  - A review of 413 salivary gland tumours in the head and neck region.
AB  - OBJECTIVES: Salivary gland tumours (SGTs) are a group of heterogeneous lesions
      with complex clinico-pathological characteristics and distinct biological
      behaviours. Previous studies have reported geographic variations in site
      distribution, incidence and histological types of SGTs. The aim of this study was
      to describe the demography of SGTs seen at a tertiary health centre and compare
      findings with previous studies. STUDY DESIGN: Data on SGTs from archives of the
      Department of Oral Pathology and the Department of Pathology, University College
      Hospital Ibadan were retrieved. Information about histological types, age, sex
      and location were analyzed using SPSS for Window (version 20.0; SPSS Inc.
      Chicago, IL). Reactive and tumor-like lesions such as sialometaplasia, benign
      lymphoepithelial lesion, lymphoepithelial cyst, mucocele, mucous extravasation
      phenomenon, ranula, and sialosis were excluded from the study. RESULTS: 413 SGTs
      consisting of 221 (53.5%) malignant and 192 (46.5%) benign lesions were seen.
      SGTs occurred more in females (50.6%) than males (49.4%) with a mean age of 43.7
      (+/-16.9) years and peak age in the fifth decade of life. The parotid with 171
      (41.4%) cases was the commonest site, followed by palate with 89 (21.5%) cases,
      while only 7(1.7%) cases were seen in sublingual gland. Pleomorphic adenoma with
      169 (40.9%) was the most frequent SGT followed by adenoid cystic carcinoma with
      93 (22.5%) cases which also was the most frequent malignant SGT while only 3
      (0.7%) cases of Warthin's tumour were seen. CONCLUSION: This report is one of few
      that showed a higher occurrence of malignant SGTs compared to their benign
      counterparts. The findings were essentially similar to findings in Africa but
      showed SGTs to be more common in females. The reason(s) for high occurrence of
      malignant SGTs in minor salivary glands and the rarity of Warthins tumour in this
      study and other African series compared to those from America needs further
      investigation. Key words:Salivary gland tumours, parotid gland, pleomorphic
      adenoma, adenoid cystic carcinoma, warthin's tumour.

PMID- 24455086
TI  - Frequency of mesiodens in the pediatric population in North India: A radiographic
      study.
AB  - OBJECTIVES: Mesiodens are the most common supernumerary teeth, occurring in 0.15%
      to 2.2% of the population. The aim of the present study was to analyze the
      frequency and radiological features of mesiodens in the pediatric population.
      MATERIAL AND METHODS: The study was based on the radiographic evaluation of 4133
      pediatric patients of the age range of 4-15 years, attending the Department of
      Oral Medicine and Radiology during the time period between September 2008 to
      December 2012. In addition to the presence of a supernumerary tooth between the 2
      central incisors, data regarding the number, position, shape and associated
      complications were also recorded. RESULTS: The prevalence of mesiodens in the
      present study was 1.4%. The prevalence was estimated using a 95% confidence
      interval. The ratio of boys to girls was 1.8:1 and majority of cases (89.7%) had
      1 mesiodens. Most of the mesiodens (59.6%) were aligned in a vertical position.
      39 mesiodens (62.9%) were impacted, while 14 (22.6%) were partially erupted and
      only 9 (14.5%) were completely erupted into occlusion. The main complication
      associated with the mesiodens was midline diastema (28.6%) and 16 patients were
      asymptomatic. CONCLUSION: Mesiodens can result in spacing in the arch, delayed or
      ectopic eruption of the permanent incisors, further altering the occlusion and
      esthetics of the patient or may remain asymptomatic. It is therefore important
      for the practitioners to diagnose a mesiodens early in development to allow for
      optimal treatment plan. Key words:Mesiodens, prevalence, pediatric population,
      midline diastema.

PMID- 24455087
TI  - Smear layer removal in canals shaped with reciprocating rotary systems.
AB  - The aim was to assess the presence of smear layer after canal instrumentation
      with two reciprocating rotary systems and a continuous motion one. Thirty canals
      were shaped with Reciproc, WaveOne or Mtwo systems. Smear layer was assessed
      following a three value scale at coronal, middle and apical levels with a
      scanning electron microscopy. Reciproc scores: coronal third, 20% of the cases:
      0, 60%: 1, 20%: 2; middle third, 10%: 0, 20%: 1, 70%:2; apical third: 2 in all
      cases. WaveOne scores: coronal third, 0 (40%), 1 (30%) and 2 (30%); middle third,
      0 (20%), 1 (50%), 2 (30%); apical third, 0 (20%), 2 (80%) of cases. MTwo scores:
      coronal third 0 (50%), 1 (30%) 2 (20%); middle third 0 (20%), 1 (50%), 2 (30%);
      apical third, 0 (10%), 1 (10%), 2 (80%). No significant differences (p>0.05) were
      found between the three used systems. Key words:Endodontics, reciprocating motion
      files, rotary file, SEM, smear layer. 

PMID- 24455088
TI  - True vertical validation in facial orthognathic surgery planning.
AB  - OBJECTIVES: To validate the effectiveness of the original standards of True
      Vertical (TV) Subnasal Line in orthognatic surgery planning. The present study
      evaluates the changes occurring in patients with skeletal Class II alterations
      programmed for orthognathic surgery with a view to improving their facial
      profile. STUDY DESIGN: [corrected] We showed a series of black profiles (composed
      by a first control group of subjects with normal occlusion, and another two
      additional groups comprised patients before -Group 2- and after orthognatic
      surgical correction of Class II malocclusion -Group 3-) for three groups of
      observers (orthodontists, surgeons and laypeople). The facial images became black
      silhouettes in order to determine a series of parameters (including aesthetic
      assessment) by means of the observers. Their observation were assessed using a 5
      point Likert scale. RESULTS: The sample was composed of 52 profile's subjects who
      were tested for a total of 72 observers. Aesthetic assessment yielded mean scores
      of 2.57, 1.67 and 2.46 for groups 1, 2 and 3, respectively. There was a
      statistically significant difference (p<0.001) between group 1 versus group 2.
      There were no significant differences in terms of observer assessment of
      aesthetics, with the exception of a wider perception range among the
      orthodontists. Regarding the studied profile measures, significant differences
      were recorded for point B' and Pg' (p<0.02) between groups 2 and 3 (i.e., pre-
      versus post-surgery). CONCLUSIONS: The results of our study suggest the subnasale
      vertical and sagittal measures of the lower third of the face are decisive in
      facial aesthetics, and therefore also for the planning of orthognathic surgery.
      Consequently, these aesthetic parameters can be used as an objective tool for the
      planning of orthodontic treatment. Key words:Facial profile, Class II,
      orthognathic surgery, cephalometric analysis, facial soft tissue, subnasale
      vertical.

PMID- 24455089
TI  - Mesiodistal crown diameters and tooth size discrepancy of permanent dentition in
      thalassemic patients.
AB  - OBJECTIVES: To provide a description of mesiodistal crown diameters (MD) and
      tooth-size discrepancy (TSD) of the permanent dentition in patients with
      thalassemia major (TM) and to compare the results with those of unaffected
      control group. STUDY DESIGN: The sample consisted of 46 thalassemic patients, 25
      males and 21 females aged 7.3 to 23.7 years (mean +/- SD = 11.2 +/- 3.9 years)
      and control group matched by age and sex. Dental casts of the participants were
      measured for MD, using a digital sliding caliper. Descriptive statistics were
      computed for each individual tooth. Student t-test was used for comparison of
      mean values between males and females as well as between thalassemic and control
      groups. The differences between sets of data were evaluated by analysis of
      variance (ANOVA). RESULTS: All means for MD of thalassemic males and females were
      smaller than their controls, with 20 of the 24 comparisons being statistically
      significant (ranged from P<0.05 to P<0.001). In both thalassemic and control
      groups, males exhibited significantly larger MD than females in most instances.
      Canines displayed the most sexual dimorphic teeth in the dentition. Lateral
      incisors showed the greatest variability indicated by the coefficient of
      variation, while the first molars were the least variable teeth (7.6% vs. 5.3%).
      There were no statistically significant differences in the anterior and overall
      tooth-size discrepancy ratios between sexes or between thalassemic and control
      groups. The mean anterior ratio (79.5%) and overall ratio (92.4%) of the control
      group were significantly larger than of Bolton ratios; P< 0.001 and P<0.05,
      respectively. CONCLUSIONS: The present study demonstrated that thalassemic males
      and females exhibited significantly smaller MD than the control group. The TSD
      ratios in both thalassemic and control groups were significantly larger than
      those of Bolton sample. These findings should be taken into account when planning
      orthodontic treatment for thalassemic patients. Key words:Permanent dentition,
      tooth size, thalassemia major.

PMID- 24455090
TI  - Evaluation of alveolar cortical bone thickness and density for orthodontic mini
      implant placement.
AB  - OBJECTIVE: Mini-implant stability is primarily related to bone quality and
      quantity. This study evaluated alveolar cortical bone thickness and density
      differences between interradicular sites at different levels from the alveolar
      crest, and assessed the differences between adolescents (12-18 years of age) and
      adults (19-50 years of age), males and females, upper and lower arch, anterior
      and posterior region of jaws and buccal and oral side. STUDY DESIGN: In this
      retrospective study, 48 Computed Tomography scans, performed for oral surgery
      purposes were selected from dental records of 3,223 Caucasian orthodontic
      patients. The SimPlant software (Materialise, Leuven, Belgium) was used to
      measure cortical bone thickness and density at 13 interradicular sites and four
      bone levels ( 2,4,6 and 8 mm ). For the statistical analysis descriptive
      statistics, Student's t-test and Pearson correlation coefficient were used.
      RESULTS: Statistically significant differences in alveolar cortical bone
      thickness and density between age, gender, sites and sides were found (P<0.05).
      The Pearson correlation coefficient demonstrated a significant linear increasing
      of thickness and density from crest to base of alveolar crest (P<=0.05).
      Conclusion. Adults show a thicker alveolar cortical bone than adolescents.
      Alveolar cortical bone thickness and density were greater in males than in
      females, in mandible than in maxilla, in the posterior region than the anterior,
      in oral than buccal side. There is an increase of thickness and density from
      crest to base of alveolar crest. Key words:Orthodontics, cortical bone thickness,
      cortical bone density, mini-implant, computed tomography, temporary anchorage
      devices.

PMID- 24455091
TI  - Evaluation of horizontal ridge augmentation using beta tricalcium phosphate and
      demineralized bone matrix: A comparative study.
AB  - OBJECTIVES: To evaluate the effectiveness of beta tricalcium phosphate (beta-TCP)
      alone compared to beta-TCP and Demineralized Bone Matrix (DBM) in regenerating
      localized horizontal maxillary alveolar ridge deficiencies prior to implant
      placement. STUDY DESIGN: The study included 20 patients with horizontal maxillary
      ridge deficiencies limited to one or more neighbouring teeth and initial ridge
      width of <= 5mmm. Patients were divided equally into two equal groups. Ridge
      augmentation was performed using Guided Bone Regeneration (GBR) principals. In
      group I GBR was performed using beta-TCP only, while in group II both beta-TCP
      and DBM were used. Following a 6 months healing period, bone cores from both
      groups were retrieved and implants were inserted. Specimens were examined
      histologically to calculate percentage of mineralized bone. Apical and crestal
      changes in ridge dimensions were calculated by digital subtraction using Cone
      Beam Computed Tomography (CBCT) immediately after graft placement and six months
      later. RESULTS: There was a statistically significant difference between the mean
      area percentage of mineralized bone between both groups where it was 40.1 %
      (range: 27.76-% 66.29 %) for group I and 68.96 % (range: 60.07 % - 87.33 %) for
      group II. Radiograpically, the mean ridge width in group I increased crestally to
      4.66 mm (range:3.5-5mm) and apically to 6.12 mm (range: 4.1-6.7 mm). In group II
      the mean ridge width increased crestally to 5.2 mm (range 4.9-5.4mm) and apically
      to 6.9 mm (range 6.0-7.8 mm). Group II showed more bone gain with a mean of 1.37
      mm crestally and 2.44 mm apically. This difference however was not statistically
      significant Conclusion: Within the limitations of this study the combination of
      DBM and beta-TCP can be used effectively in cases exhibiting minimal alveolar
      ridge defects. Key words:Guided bone regeneration, equine bone, alloplast, bone
      graft.

PMID- 24455092
TI  - Fractographic study of the behavior of different ceramic veneers on full coverage
      crowns in relation to supporting core materials.
AB  - OBJECTIVES: To observe porcelain veneer behavior of zirconia and metal-ceramic
      full coverage crowns when subjected to compression testing, comparing zirconia
      cores to metal cores. STUDY DESIGN: The porcelain fracture surfaces of 120 full
      coverage crowns (60 with a metal core and 60 with a zirconia core) subjected to
      static load (compression) testing were analyzed. Image analysis was performed
      using macroscopic processing with 8x and 12x enlargement. Five samples from each
      group were prepared and underwent scanning electron microscope (SEM) analysis in
      order to make a fractographic study of fracture propagation in the contact area
      and composition analysis in the most significant areas of the specimen. RESULTS:
      Statistically significant differences in fracture type (cohesive or adhesive)
      were found between the metal-ceramic and zirconia groups: the incidence of
      adhesive fracture was seen to be greater in metal-ceramic groups (92%) and
      cohesive fracture was more frequent in zirconium oxide groups (72%). The fracture
      propagation pattern was on the periphery of the contact area in the full coverage
      crown restorations selected for fractographic study. CONCLUSIONS: The greater
      frequency of cohesive fracture in restorations with zirconia cores indicates that
      their behavior is inadequate compared to metal-ceramic restorations and that
      further research is needed to improve their clinical performance. Key
      words:Zirconia, zirconium oxide, fractography, composition, porcelain veneers,
      fracture, cohesive, adhesive.

PMID- 24455093
TI  - Rehabilitation with implant-supported overdentures in total edentulous patients:
      A review.
AB  - OBJECTIVES: The main aim of this review article is to discuss implant-supported
      overdentures (ISOs) as treatment in edentulous patients. Besides, we will try to
      discuss among the different treatment options in such patients and to analyze
      their validity when ISOs are compared with other clinical modalities. At the same
      time, we will try to suggest clinical guidelines supported by current clinical
      studies. MATERIAL AND METHODS: We performed a Medline search and review of
      pertinent articles on the mentioned subject from 1986 to 2011. As a searching
      strategy, we used the following words: implant-supported overdentures, attachment
      systems, Locator attachment, cantilever, fixed prosthesis. RESULTS AND
      CONCLUSIONS: Implant-supported overdentures constitute an accurate and
      predictable treatment option and achieve a higher patients' satisfaction. This
      type of treatment constitutes a cheaper treatment than fixed prostheses and in
      some patients, with loss of lip support or with an interoclusal space larger than
      15 mm, the choice of implant-supported overdentures seems to prevent future
      aesthetic or phonetic problems. Key words:Overdentures, implant occlusion,
      implant rehabilitation, total edentulous rehabilitation, fixed prosthesis.

PMID- 24455094
TI  - Alternative to oral dicoumarin anticoagulants: Considerations in dental care.
AB  - INTRODUCTION: For over 50 years, vitamin K antagonists such as warfarin
      (Aldocumar(r)) and acenocoumarol (Sintrom(r)) have been the gold standard for
      reducing the risk of cerebrovascular events. In the last 5 years alternative
      anticoagulants have been evaluated that act directly upon a concrete target
      within the coagulation cascade, thereby affording a more predictable
      anticoagulant effect. The present study offers an update on the new oral
      anticoagulants and reviews the implications referred to the dental care of
      patients administered these substances. MATERIAL AND METHODS: An exhaustive
      PubMed-Medline and Cochrane Library search was made of the main alternatives to
      conventional oral anticoagulation, covering those studies published in English
      and Spanish over the last 10 years. Specialized textbooks and pharmaceutical
      catalogs were also consulted. A total of 184 articles were identified, of which
      76 met the inclusion criteria. RESULTS: The new oral anticoagulants dabigatran,
      rivaroxaban and apixaban are safe and effective, and offer a series of
      advantages, including rapid action, no need for constant monitoring, few drug and
      food interactions, and a broad therapeutic margin. These drugs are expensive,
      however, and some lack a specific antidote, while others must be administered
      twice a day. Regarding the dental treatment of patients receiving these drugs,
      suspension or modification of the background medication is not required when
      performing invasive dental procedures, except where indicated by the prescribing
      physician. CONCLUSIONS: The new oral anticoagulants do not pose significantly
      greater risks than conventional oral anticoagulants when providing invasive
      dental treatment, and their suspension is not strictly required in such
      situations. Key words:Dabigatran, rivaroxaban, apixaban, dental, hemostasis.

PMID- 24455095
TI  - Clinical and microbiological diagnosis of oral candidiasis.
AB  - INTRODUCTION: Candidiasis or oral candidiasis is the most frequent mucocutaneous
      mycosis of the oral cavity. It is produced by the genus Candida, which is found
      in the oral cavity of 53% of the general population as a common commensal
      organism. One hundred and fifty species have been isolated in the oral cavity,
      and 80% of the isolates correspond to Candida albicans, which can colonize the
      oral cavity alone or in combination with other species. Transformation from
      commensal organism to pathogen depends on the intervention of different
      predisposing factors that modify the microenvironment of the oral cavity and
      favor the appearance of opportunistic infection. The present study offers a
      literature review on the diagnosis of oral candidiasis, with the purpose of
      establishing when complementary microbiological techniques for the diagnosis of
      oral candidiasis should be used, and which techniques are most commonly employed
      in routine clinical practice in order to establish a definitive diagnosis.
      MATERIALS AND METHODS: A Medline-PubMed, Scopus and Cochrane search was made
      covering the last 10 years. RESULTS: The diagnosis of oral candidiasis is
      fundamentally clinical. Microbiological techniques are used when the clinical
      diagnosis needs to be confirmed, for establishing a differential diagnosis with
      other diseases, and in cases characterized by resistance to antifungal drugs.
      Biopsies in turn are indicated in patients with hyperplastic candidiasis.
      Staining (10% KOH) and culture (Sabouraud dextrose agar) are the methods most
      commonly used for diagnosing primary candidiasis. Identification of the
      individual species of Candida is usually carried out with CHROMagar Candida(r).
      For the diagnosis of invasive candidiasis, and in cases requiring differentiation
      between C. albicans and C. dubliniensis, use is made of immunological and genetic
      techniques such as ELISA and PCR. Key words:Clinical, oral candidiasis,
      microbiology.

PMID- 24455096
TI  - Diffuse large B-cell lymphoma, not otherwise specified of the palate: A case
      report.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin's
      lymphoma found in oral and maxillofacial regions. A large number of cases may be
      biologically heterogeneous, which are commonly defined as DLBCL, not otherwise
      specified (NOS) by the World Health Organization (WHO-2008). The present case
      reports on an ulcer of raised and irregular edges, found on the border between
      the hard and soft palate, as the first and only manifestation of an extranodal
      non-Hodgkin lymphoma in an 85-year-old patient. Incisional biopsy was carried
      out, and the specimen revealed a proliferation of large lymphoid cells suggestive
      of diffuse large cell lymphoma. An immunohistochemical analysis was performed.
      EBV-RNA was assessed by in situ hybridization that also proved to be negative.
      Immunohistochemical and EBV analyses are important to avoid delays and
      inappropriate treatment strategies. Although advanced age is considered an
      adverse prognostic factor, early diagnosis did prove to be a key contributory
      factor in the cure of non-Hodgkin lymphoma. Key words:Diffuse large B-cell
      lymphoma, elderly, EBV. 

PMID- 24455097
TI  - Endodontic management of open apex using MTA and platelet - rich fibrin membrane
      barrier: A newer matrix concept.
AB  - OBJECTIVES: Endodontic management of open apex using MTA and platelet - rich
      fibrin membrane as an apical matrix barrier. STUDY DESIGN: An immature tooth with
      pulpal necrosis and periapical pathology imposes a great difficulty to the
      endodontist. Endodontic treatment options for such teeth consist of conventional
      apexification procedure with and without apical barriers. This article
      demonstrates the use of an apical matrix barrier in form of a platelet rich
      fibrin membrane for stabilization of MTA in root end apexification procedure. PRF
      is an autologous fibrin matrix containing a large quantity of platelet and
      leukocyte cytokines, which enhance healing by release of growth factors. These
      case reports present apexification and successful healing with combined use of
      MTA and PRF membrane as an apical barrier Results: PRF membrane can serve as an
      efficient apical matrix for condensation of MTA. Combination of PRF membrane and
      MTA is an effective method for management of difficult cases of open apex. PRF is
      a strong fibrin membrane enriched with platelet and growth factors that
      accelerate periapical healing. Key words:Apexification, apical barrier, platelet
      rich fibrin (PRF), mineral trioxide (MTA).

PMID- 24455098
TI  - The largest bilateral gemination of permanent maxillary central incisors: Report
      of a case.
AB  - Gemination is defined as an attempt to make two teeth from one enamel organ.
      Bilateral presentation of this phenomenon is very rare, with prevalence of 0.01%
      to 0.04% in the primary, and 0.05% in the permanent dentition. This paper
      describes a rare case of huge bilateral gemination of permanent maxillary central
      incisors in a nine-year-old Iranian boy with poor aesthetic. The patient did not
      have history of anomaly in his primary dentition and in his family either. This
      type of dental anomaly can cause clinical problems in the form of malocclusion,
      poor aesthetic, and impaction of adjacent teeth, caries, and periodontal
      destruction. Key words:Gemination, central incisor, bilateral. 

PMID- 24455099
TI  - Squamous odontogenic tumor-like proliferation in a radicular cyst: A case report.
AB  - The squamous odontogenic tumour is a rare benign neoplasm whose aetiology remains
      unknown. It usually appears in the jaw and its origin could be related to the
      ephitelial remnants of Malassez. Histologically comprises numerous islets of
      squamous, non-keratinized, well-differentiated and rounded epithelial cells a
      fibrous stroma without signs of atypical cells. There is a non-neoplastic lesion
      with the same histological pattern than the squamous odontogenic tumour. This
      entity is characterized by squamous odontogenic tumour proliferations isolated
      into the cyst wall of an odontogenic cyst. It is rare and has a benign behavior.
      It has been suggested that these epithelial proliferations could be the former
      expression of the neoplastic form. It is very important to carry out clinical and
      radiological controls periodically. So far it has not been documented any change
      towards a squamous odontogenic tumour nor toward malignancy in a squamous
      odontogenic tumour like proliferation. Key words:Radicular cyst, squamous
      odontogenic tumour. 

PMID- 24455100
TI  - Extensive fragmentation of the X chromosome in the bed bug Cimex lectularius
      Linnaeus, 1758 (Heteroptera, Cimicidae): a survey across Europe.
AB  - Variation in the number of chromosomes was revealed in 61 samples of Cimex
      lectularius Linnaeus, 1758 from the Czech Republic and other European countries,
      hosted on Myotis Kaup, 1829 (4) and Homo sapiens Linnaeus, 1758 (57). The
      karyotype of all the specimens of Cimex lectularius analysed contained 26
      autosomes and a varying number of the sex chromosomes. The number of sex
      chromosomes showed extensive variation, and up to 20 fragments were recorded.
      Altogether, 12 distinct karyotypes were distinguished. The male karyotypes
      consisted of 29, 30, 31, 32, 33, 34, 35, 36, 37, 40, 42 and 47 chromosomes. The
      females usually exhibited the number of chromosomes which was complementary to
      the number established in the males from the same sample. However, 11 polymorphic
      samples were revealed in which the karyotypes of females and males were not
      complementary each other. The complement with 2n = 26+X1X2Y was found in 44% of
      the specimens and 57,4% samples of bed bugs studied. The karyotypes with higher
      chromosome numbers as well as individuals with chromosomal mosaics were usually
      found within the samples exhibiting particularly extensive variation between
      individuals, and such complements were not found within samples contaning a few
      or single specimen. The occurrence of chromosomal mosaics with the karyotype
      constitution varying between cells of single individual was observed in five
      specimens (4.3%) from five samples. We assume that polymorphism caused by
      fragmentation of the X chromosome may result in meiotic problems and non
      disjunction can produce unbalanced gametes and result in lowered fitness of
      individuals carrying higher numbers of the X chromosome fragments. This effect
      should be apparently enhanced with the increasing number of the fragments and
      this may be the reason for the observed distribution pattern of individual
      karyotypes in the studied samples and the rarity of individuals with extremely
      high chromosome numbers. The assumed lowering of the fitness of individuals
      carrying higher numbers of the X chromosome fragments could affect population
      dynamics of variable populations. 

PMID- 24455101
TI  - Cytological investigations and new chromosome number reports in yarrow (Achillea
      millefolium Linnaeus, 1753) accessions from Iran.
AB  - In this study, a new chromosome number for Iranian yarrow (Achillea millefolium
      L.) accessions was reported. Cytological analyses on four Achillea millefolium
      accessions, indicated that two accessions were diploids (2n=2x=18) and two
      tetraploids (2n=4x=36). Cluster analysis based on chromosomal characteristics and
      karyotype asymmetry, categorized the four accessions separated into two groups.
      In terms of the Stebbins' system, the karyotype of diploid accessions grouped in
      2A class. The average value of the total form percentage (TF%) in the group one
      (diploid accessions) and two (tetraploid accessions) were 40.85 and 41.15,
      respectively. The group one had the highest mean value for the symmetry index
      (S%=57.5). Consequently, it can be inferred that diploids belonging to the group
      one are the earlier evolutionary forms. 

PMID- 24455102
TI  - Karyotypic similarities between two species of Rhamphichthys (Rhamphichthyidae,
      Gymnotiformes) from the Amazon basin.
AB  - The family Rhamphichthyidae includes three genera: Rhamphichthys Muller et
      Troschel, 1846, Gymnorhamphichthys M. M. Ellis, 1912 and Iracema Triques, 1996.
      From this family, only the species Rhamphichthys hanni Meinken, 1937 has had its
      karyotype described. Here, we describe the karyotypes of two additional
      Rhamphichthys species: Rhamphichthys marmoratus Castelnau, 1855 from the Reserva
      de Desenvolvimento Sustentavel Mamiraua, Amazonas state and Rhamphichthys prope
      rostratus Linnaeus, 1766 from Para state, both in Brazil. Our karyotypic analyses
      demonstrated that the diploid number is conserved for the genus (2n = 50), but
      the karyotypic formulas (KFs) differed between Rhamphichthys marmoratus
      (44m/sm+6a) and Rhamphichthys prope rostratus (42m/sm+8a). In both species, the
      constitutive heterochromatin (CH) was located in the centromeric region of most
      chromosomes. Large heterochromatic blocks were found on the long arms of pairs 4
      and 14 in Rhamphichthys marmoratus and on chromosomes 3, 4 and 19 in
      Rhamphichthys prope rostratus, which also has a heteromorphism in chromosome pair
      1. The CH was DAPI positive, indicating that it is rich in AT base pairs. The
      Nucleolus Organizer Region (NOR) showed staining at a single location in both
      species: the long arm of pair 1 in Rhamphichthys marmoratus and the long arm of
      pair 12 in Rhamphichthys prope rostratus, where it showed a size heteromorphism.
      CMA3 staining coincided with that of Ag-NOR, indicating that the ribosomal genes
      contain interspaced GC-rich sequences. FISH with an 18S rDNA probe confirmed that
      there is only one NOR site in each species. These results can be used as
      potential cytogenetic markers for fish populations, and comparative analysis of
      the karyotypes of Hypopygus Hoedman, 1962, Rhamphichthys and Steatogenys
      Boulenger, 1898 suggests that the first two genera diverged later that the third.

PMID- 24455103
TI  - Karyotypes, B-chromosomes and meiotic abnormalities in 13 populations of Alebra
      albostriella and A. wahlbergi (Hemiptera, Auchenorrhyncha, Cicadellidae) from
      Greece.
AB  - In this work 13 populations of the leafhopper species Alebra albostriella
      (Fallen, 1826) (6 populations) and A. wahlbergi (Boheman, 1845) (7 populations)
      (Cicadellidae: Typhlocybinae) from Greece were studied cytogenetically. We
      examined chromosomal complements and meiosis in 41 males of A. albostriella
      sampled from Castanea sativa, Fagus sylvatica and Quercus cerris and in 21 males
      of A. wahlbergi sampled from C. sativa, Acer opalus and Ulmus sp. The species
      were shown to share 2n = 22 + X(0) and male meiosis of the chiasmate preductional
      type typical for Auchenorrhyncha. In all populations of A. albostriella and in
      all but two populations of A. wahlbergi B chromosomes and/or different meiotic
      abnormalities including the end-to-end non-homologous chromosomal associations,
      translocation chains, univalents, anaphasic laggards besides aberrant sperms were
      encountered. This study represents the first chromosomal record for the genus
      Alebra and one of the few population-cytogenetic studies in the Auchenorrhyncha. 

PMID- 24455105
TI  - On the potential roles of ticks and migrating birds in the ecology of West Nile
      virus.
AB  - BACKGROUND: Mosquitoes are the primary vectors of West Nile virus (WNV). Ticks
      have, however, been suggested to be potential reservoirs of WNV. In order to
      investigate their role in the spread of the virus, ticks, which had been
      collected from birds migrating northwards from Africa to Europe, were analyzed
      for the potential presence of WNV-RNA. METHODS: On the Mediterranean islands
      Capri and Antikythira a total of 14,824 birds were captured and investigated from
      which 747 ticks were collected. RESULTS AND CONCLUSION: Most of the identified
      ticks (93%) were nymphs and larvae of Hyalomma marginatum sensu lato, most of
      which were or appear to be Hyalomma rufipes. Of these ticks 729 were individually
      screened for WNV-RNA. None of the ticks was found to be WNV positive. Thus, there
      was no evidence that Hyalomma marginatum s.l. ticks play a role in the spread of
      WNV from Africa to Europe.

PMID- 24455104
TI  - The role of phenotypic switching in the basic biology and pathogenesis of Candida
      albicans.
AB  - The "white-opaque" transition in Candida albicans was discovered in 1987. For the
      next fifteen years, a significant body of knowledge accumulated that included
      differences between the cell types in gene expression, cellular architecture and
      virulence in cutaneous and systemic mouse models. However, it was not until 2002
      that we began to understand the role of switching in the life history of this
      pathogen, the role of the mating type locus and the molecular pathways that
      regulated it. Then in 2006, both the master switch locus WORI and the pheromone
      induced white cell biofilm were discovered. Since that year, a number of new
      observations on the regulation and biology of switching have been made that have
      significantly increased the perceived complexity of this fascinating phenotypic
      transition. 

PMID- 24455106
TI  - Detection of antibodies against H5 and H7 strains in birds: evaluation of
      influenza pseudovirus particle neutralization tests.
AB  - INTRODUCTION: Avian influenza viruses circulate in bird populations, and it is
      important to maintain and uphold our knowledge of the viral strains that are
      currently of interest in this context. Here, we describe the use of hemagglutinin
      pseudotype retroviruses based on highly pathogenic influenza viruses for the
      screening of avian sera for influenza A antibodies. Our aim was also to determine
      whether the pseudovirus neutralization tests that we assessed were sensitive and
      simple to use compared to the traditional methods, including hemagglutination
      inhibition assays and microneutralization tests. MATERIAL AND METHODS: H5 and H7
      pseudovirus neutralization tests were evaluated by using serum from infected
      rabbits. Subsequently, the assays were further investigated using a panel of
      serum samples from avian species. The panel contained samples that were
      seropositive for five different hemagglutinin subtypes as well as influenza A
      seronegative samples. RESULTS AND DISCUSSION: The results suggest that the
      pseudovirus neutralization test is an alternative to hemagglutination inhibition
      assays, as we observed comparable titers to those of both standard
      microneutralizations assays as well as hemagglutinin inhibition assays. When
      evaluated by a panel of avian sera, the method also showed its capability to
      recognize antibodies directed toward low-pathogenic H5 and H7. Hence, we conclude
      that it is possible to use pseudoviruses based on highly pathogenic avian
      influenza viruses to screen avian sera for antibodies directed against influenza
      A subtypes H5 and H7.

PMID- 24455107
TI  - Transmission of hepatitis C virus among intravenous drug users in the Uppsala
      region of Sweden.
AB  - BACKGROUND: Epidemiology and transmission patterns of hepatitis C virus (HCV) are
      important subjects as we enter a new era of treatment with directly acting
      antivirals (DAAs). The highest prevalence of HCV in developed countries is found
      among intravenous drug users (IDUs), where unsafe needle sharing practices
      provide the main route of infection. Efforts to prohibit the continuous spread of
      HCV among these groups have been initiated by the community services and health
      care providers. Our goal was to understand how HCV was transmitted among IDUs
      within a limited population group. We provide a retrospective study (2005-2007)
      of the HCV transmission patterns in a population of IDUs in the Uppsala region of
      Sweden. METHOD: Eighty-two serum samples were collected from IDUs in Uppsala
      County. Our reverse transcription nested polymerase chain reaction (RT-nested
      PCR) and sequencing method enabled a comprehensive genetic analysis for a broad
      spectrum of genotypes of two relatively conserved regions, NS5B and NS3, that
      encodes for the viral polymerase and protease, respectively. HCV RNA in serum
      samples was amplified and sequenced with in-house primers. Sequence similarities
      between individuals and subgroups were analyzed with maximum likelihood (ML)
      phylogenetic trees. Published HCV reference sequences from other geographic
      regions and countries were also included for clarity. RESULTS: Phylogenetic
      analysis was possible for 59 NS5B (72%) and 29 NS3 (35%) sequences from Uppsala
      patients. Additionally, we also included 15 NS3 sequences from Orebro patients,
      making a total of 44 NS3 sequences for the analysis. By analyzing the NS3
      sequences, two transmission sets were found between the IDUs (>98% sequence
      identity), with one set consisting of two individuals and another set consisting
      of three individuals. In addition, the phylogenetic analysis done with our serum
      samples displayed clusters that distinguished them from the reference sequences.
      CONCLUSION: Our method seems to enable us to trace the HCV transmission between
      IDUs. Furthermore, the method is fairly independent of the time of infection
      because the method uses relatively conserved HCV sequence regions (i.e. NS5B and
      NS3).

PMID- 24455108
TI  - The Spanish flu in Uppsala, clinical and epidemiological impact of the influenza
      pandemic 1918-1919 on a Swedish county.
AB  - INTRODUCTION AND AIM: The Spanish flu reached Sweden in June 1918, and at least
      one-third of the population (then 5.8 million) became infected. Some 34,500
      persons (5.9 per 1,000 people) died from influenza during the first year of the
      pandemic (when acute pneumonia is included, the number of deaths rose to 7.1 per
      1,000 people). In this historical look back at the pandemic, our aim was to
      review the epidemiological impact on the Swedish county of Uppsala, the clinical
      outcomes and the economic impact on the regional hospital; a relevant backgound
      to consider the impact of a future virulent pandemic. We also focused on how the
      pandemic was perceived by the medical community and by health care authorities.
      METHODS: Health care reports, statistics, daily newspapers, medical journals, and
      records of patients treated for influenza at the Uppsala Academic Hospital from
      July 1918 to June 1919 were included in our review. RESULTS: An influenza related
      mortality rate of 693 persons (5.1 per 1,000 people) was reported in the Uppsala
      region from 1918-1919; from July 1918 to June 1919, 384 patients were treated for
      influenza at the Uppsala Academic Hospital. The first wave peaked in November
      1918 with case fatality rates up to 30%; a second wave peaked in April 1919 with
      a lower rate of mortality. Of the patients treated, a total of 66 died. Of these,
      60% were 20-29 years of age, and 85% were less than 40 years old. Autopsy reports
      revealed pneumonia in 89% of the cases; among these, 47% were hemorrhagic, 18%
      were bilateral, and 45% had additional extrapulmonary organ involvement. Signs of
      severe viral disease were documented, but secondary bacterial disease was the
      primary cause of death in the majority of cases. CONCLUSION: The epidemiologic
      and pathologic results were in accordance with other publications of this time
      period. The costs of running the hospital doubled from 1917 to 1920 and then
      reversed by 45%. Today, an influenza pandemic of the same virulence would
      paralyze health care systems and result in extremely high financial costs and
      rates of mortality.

PMID- 24455109
TI  - Cryo-electron microscopy of extracellular vesicles in fresh plasma.
AB  - INTRODUCTION: Extracellular vesicles (EV) are phospholipid bilayer-enclosed
      vesicles recognized as new mediators in intercellular communication and potential
      biomarkers of disease. They are found in many body fluids and mainly studied in
      fractions isolated from blood plasma in view of their potential in medicine. Due
      to the limitations of available analytical methods, morphological information on
      EV in fresh plasma is still rather limited. OBJECTIVES: To image EV and determine
      the morphology, structure and size distribution in fresh plasma by cryo-electron
      microscopy (cryo-EM). METHODS: Fresh citrate- and ethylenediaminetetraacetic acid
      (EDTA)-anticoagulated plasma or EV isolated from these plasmas were rapidly cryo
      immobilized by vitrification and visualized by cryo-EM. RESULTS: EV isolated from
      fresh plasma were highly heterogeneous in morphology and size and mostly contain
      a discernible lipid bilayer (lipid vesicles). In fresh plasma there were 2 types
      of particles with a median diameter of 30 nm (25-260 nm). The majority of these
      particles are electron dense particles which most likely represent lipoproteins.
      The minority are lipid vesicles, either electron dense or electron lucent, which
      most likely represent EV. Lipid vesicles were occasionally observed in close
      proximity of platelets in citrate and EDTA-anticoagulated platelet-rich plasma.
      Cryo-electron tomography (cryo-ET) was employed to determine the 3D structure of
      platelet secretory granules. CONCLUSIONS: Cryo-EM is a powerful technique that
      enables the characterization of EV in fresh plasma revealing structural details
      and considerable morphological heterogeneity. Only a small proportion of the
      submicron structures in fresh plasma are lipid vesicles representing EV.

PMID- 24455110
TI  - Kikuchi-fujimoto disease in the United States: three case reports and review of
      the literature [corrected].
AB  - Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing
      lymphadenitis [corrected], is a benign, self-limiting disease that manifests
      primarily as cervical lymphadenopathy but may include low-grade fever, headache,
      and fatigue. There is a higher incidence of KFD in women aged 20-35 years and in
      Asian populations. A PubMed search revealed 590 articles that described KFD. Of
      these, 22 cases have been fully described in the United States. Ten of the 22
      (45%) patients were male and 12 (55%) were female, with 20% Caucasian, 20% Asian
      American, and the remaining 60% of other ethnic backgrounds. In this study, we
      describe an additional 3 cases of KFD and discuss the diagnosis, pathology, and
      management of KFD.

PMID- 24455111
TI  - Comparative evaluation of bone marrow aspirate with trephine biopsy in
      hematological disorders and determination of optimum trephine length in lymphoma
      infiltration.
AB  - INTRODUCTION: Bone marrow examination is an indispensable diagnostic tool to
      evaluate neoplastic and non neoplastic hematological diseases. AIMS: To compare
      bone marrow aspirate with trephine biopsy in hematological disorders. To
      determine the optimum trephine preprocessing length in lymphoma infiltration.
      METHODS: Diagnostic comparison was done between simultaneous bone marrow
      aspirates and trephine biopsies in 449 patients. Biopsies were fixed in formalin,
      decalcified in 5.5% EDTA and routinely processed. Concordance rates and validity
      parameters for aspirate were calculated. Three deeper sections of trephine
      biopsy, cut at 0.1-0.2 mm intervals, were assessed for lymphoma involvement.
      Proportion of biopsies showing marrow infiltration by lymphoma cells was plotted
      against trephine length and correlation was assessed. RESULTS: Aspirate had a
      high sensitivity for acute leukemia (89.4%) and multiple myeloma (88.5%),
      moderate for NHL (67.6%) and nonhematopoietic metastases (58.3%) and low for
      aplastic anemia (38.5%) and Hodgkin lymphoma (5%). Aspirate has no role in
      granulomatous myelitis and myelofibrosis. Lymphoma positivity increased with
      trephine length, with maximum positivity (68.9%) seen in 17-20 mm group and no
      further gain beyond 20 mm. (lymphoma positivity <=16mm=40.3% and >=17mm=66.1%,
      p=0.0011). CONCLUSION: Aspirate has a high specificity; its sensitivity depends
      upon the type of disease. Apart from few conditions, in which aspirate alone is
      sufficient, biopsy is mandatory in most. Preprocessing trephine length of 17-20
      mm examined at multiple deeper levels was found optimal for assessing lymphoma
      positivity.

PMID- 24455112
TI  - Second-Generation Tyrosine Kinase Inhibitors (Tki) as Salvage Therapy for
      Resistant or Intolerant Patients to Prior TKIs.
AB  - With the advent of target therapies, imatinib became the mainstay for treatment
      of chronic myeloid leukemia. However, despite the brilliant results obtained with
      this drug, more than 30% of patients discontinue therapy in long-term due to
      several reasons, including failure and/or intolerance. Second-generation tyrosine
      kinase inhibitors (TKIs) are more potent drugs and have expanded inhibition
      against a broad spectrum of mutations resistant to imatinib. Both nilotinib and
      dasatinib have demonstrated in vitro and in vivo clinical activity against
      different types of mutations and various forms of resistance. However, patients
      with T315I mutation do not obtain an advantage from these drugs and a third
      generation inhibitor ponatinib, a pan-BCR drug, was tested with significant
      results. In this review, we report the results of second-and third-generation
      TKIs tested as second or third line therapy in patients resistant and/or
      intolerant to previous inhibitors. 

PMID- 24455113
TI  - Distribution of Different PML/RARalpha bcr Isoforms in Indian Acute Promyelocytic
      Leukemia (APL) Patients and Clinicohematological Correlation.
AB  - CONTEXT: Acute promyelocytic leukemia (APL), an AML subtype, is characterized
      morphologically by abnormal promyelocytes. Molecular studies show three possible
      bcr isoforms of PML-RARalpha fusion gene. This study undertakes analysis of PML
      RARalpha bcr isoforms and their correlation with haematological parameters and
      response to treatment in Indian patients. AIMS: To study different PML-RARalpha
      bcr isoforms in Indian patients and to find any correlation with various
      haematological parameters and response to treatment. SETTINGS AND DESIGN:
      Patients diagnosed as APL on morphology or flowcytometry and confirmed by RQ PCR
      were included in the study. Treated APL patients or patients with relapse and on
      follow-up were excluded from the study. METHODS AND MATERIAL: Twenty patients
      over thirty one months period were included. The clinical, haematological &
      morphological features were analysed, the latter using routine & special
      cytochemical stains on blood and bone marrow. Flow cytometric evaluation using 4
      color Beckman Coulter FC 500 and molecular studies using RT PCR Fusion Quant(r)
      kits for bcr-1, bcr-2 and bcr-3 of PML-RARalpha bcr isoforms on the instrument
      Rotor GeneTM 3000 were performed. STATISTICAL ANALYSIS USED: Student t test was
      applied to correlate different bcr isoforms with various haematological
      parameters and response to treatment. RESULTS: In our study, M:F ratio was 1.5:1
      with median age 42 years, Hb - 8.0 g/dl, TLC-7900/MUl, and platelet - 35000/MUl
      and varied clinical presentation. Four patients were microgranular variants, and
      the rest were hypergranular. MPO and CAE positivity were100% and for NSE it was
      33.33%. Molecular analysis revealed PML-RARalpha isoforms of bcr1 in 42.85%, bcr2
      in 14.28% and bcr3 in 38.09% patients. No correlation was found between PML
      RARalpha bcr isoforms, different haematological parameters and response to
      treatment. CONCLUSIONS: Higher incidence of PML-RARalpha bcr-1 isoform was found
      in Indian APL patients with no significant correlation between different
      haematological parameters and response to treatment.

PMID- 24455114
TI  - Treatment recommendations for chronic myeloid leukemia.
AB  - The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation
      and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved
      the quality of life during the chronic phase of the disease, without preventing
      nor significantly delaying the progression towards advanced phases. The
      introduction of allogeneic stem cell transplantation (alloSCT) marked the first
      important breakthrough in the evolution of CML treatment, because about 50% of
      the eligible patients were cured. The second breakthrough was the introduction of
      human recombinant interferon-alfa, able to achieve a complete cytogenetic
      remission in 15% to 30% of patients, with a significant survival advantage over
      conventional chemotherapy. At the end of the last century, about 15 years ago,
      all these treatments were quickly replaced by a class of small molecules
      targeting the tyrosine kinases (TK), which were able to induce a major molecular
      remission in most of the patients, without remarkable side effects, and a very
      prolonged life-span. The first approved TK inhibitor (TKI) was Imatinib Mesylate
      (Glivec or Gleevec, Novartis). Rapidly, other TKIs were developed tested and
      commercialized, namely Dasatinib (Sprycel, Bristol-Myers Squibb), Nilotinib
      (Tasigna, Novartis), Bosutinib (Busulif, Pfizer) and Ponatinib (Iclusig, Ariad).
      Not all these compounds are available worldwide; some of them are approved only
      for second line treatment, and the high prices are a problem that can limit their
      use. A frequent update of treatment recommendations is necessary. The current
      treatment goals include not only the prevention of the transformation to the
      advanced phases and the prolongation of survival, but also a length of survival
      and of a quality of life comparable to that of non-leukemic individuals. In some
      patient the next ambitious step is to move towards a treatment-free remission.
      The CML therapy, the role of alloSCT and the promising experimental strategies
      are reviewed in the context of the new therapeutic goals. 

PMID- 24455115
TI  - Tyrosine kinase inhibitors and interferon.
AB  - The use of interferon-a (INF) in chronic myeloid leukemia, when it started in the
      80s, was considered as a breakthrough in the therapy of this disease; INF
      administered alone or in combination with aracytin was the standard choice for
      treatment for Chronic Myeloid Leukemia (CML) patients unfit for bone marrow
      transplantation. With the appearance of the first Tyrosine Kinase Inhibitor (TKI)
      (imatinib) and based on the results of the pivotal IRIS trial, imatinib
      monotherapy was the new treatment of choice for CML, according to the ELN
      recommendations. The possibility of combining INF with imatinib, for obtaining
      better therapeutic responses in CML patients has been already tested and
      reported. The current challenge is the combined use of second generation TKIs
      with pegylated -IFN, in order to minimize failures to therapy and increase the
      number of CML patients with deep molecular responses, who may be able to
      discontinue lifelong treatment. 

PMID- 24455117
TI  - Status Epilepticus due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell
      Transplant Recipient.
AB  - Reactivation of human herpes virus-6 (HHV-6) after stem cell transplantation
      occurs frequently. It is associated with clinical manifestations varying from
      nonspecific symptoms such as fevers or rash, to severe life threatening
      complications including post-transplantation limbic encephalitis. We report a
      case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem
      cell transplant recipient who presented with status epilepticus unresponsive to
      antiepileptic therapy. With intravenous ganciclovir and supportive care, the
      patient's condition improved. Awareness of HHV-6 infection in stem cell
      transplant recipients may help with early diagnosis and improved outcome. 

PMID- 24455116
TI  - Imatinib in chronic myeloid leukemia: an overview.
AB  - Imatinib was the first signal transduction inhibitor (STI), used in a clinical
      setting. It prevents a BCR-ABL protein from exerting its role in the oncogenic
      pathway in chronic myeloid leukemia (CML). Imatinib directly inhibits the
      constitutive tyrosine kinase activity. Imatinib binds to BCR-ABL kinase domain by
      preventing the transfer of a phosphate group to tyrosine on the protein substrate
      and the subsequent activation of phosphorylated protein. As the result, the
      transmission of proliferative signals to the nucleus is blocked and leukemic cell
      apoptosis is induced. The FDA has approved imatinib as first-line treatment for
      newly diagnosed CML in December 2002 following an International Randomized Study
      (IRIS), initiated in June 2000, comparing imatinib at a single daily dose 400 mg
      to IFN alpha plus cytarabine in newly diagnosed patients with CML in CP. Results
      from this study show the outstanding effectiveness of imatinib and its
      superiority with respect to the rates of complete hematological response (CHR),
      major and complete cytogenetic response (MCyR, CCyR). Patients randomized to
      imatinib arm at 8 - year data cut off continue to have a durable hematologic and
      cytogenetic responses, low progression rates to AP or BC, and remarkable survival
      outcomes. An overall survival (OS) rate is 85% for patients receiving imatinib
      (93% when only CML-related deaths and those prior to stem cell transplantation
      are considered). The results have been confirmed in the last years by several
      groups. According these cumulative results the rates of CCyR achieved after one
      year of therapy with imatinib at standard dose ranged from 49% to 77%, and the
      proportion of patients who achieved major molecular response (MMR) after one year
      ranged between 18% and 58%. Discontinuation of imatinib has been also tried in
      patients in MMR, a molecular relapse occurs in about one third of patients,
      generally within 6 months from imatinib cessation. 

PMID- 24455118
TI  - Monitoring the Response to Tyrosine Kinase Inhibitor (TKI) Treatment in Chronic
      Myeloid Leukemia (CML).
AB  - The aim of oral tyrosine kinase inhibitor (TKI) treatment in chronic myeloid
      leukemia (CML) is to get ideal hematological, cytogenetic, molecular responses at
      the critical time points. The depth of the response obtained with TKI and the
      time to achieve this response are both important in predicting the prognosis in
      patients with CML. The high efficacy of the TKI treatment of CML has prompted the
      need for accurate methods to monitor response at levels below the landmark of
      CCyR. Quantification of BCR-ABL transcripts has proven to be the most sensitive
      method available and has shown prognostic impact with regard to progression-free
      survival. European LeukemiaNet (ELN) molecular program harmonized the reporting
      of results according to the IS (International harmonization of Scale) in Europe.
      The aim of this review is to outline monitoring the response to optimal TKI
      treatment based on the ELN CML 2013 recommendations from the clinical point of
      view as a physician. Careful cytogenetic and molecular monitoring could help to
      select the most convenient TKI drug and to optimize TKI treatment. Excessive
      monitoring may have an economic cost, but failure to optimize TKI treatment may
      result in CML disease acceleration and death. 

PMID- 24455119
TI  - A critical history of chromic myeloid leukemia.

PMID- 24455120
TI  - The density and spatial arrangement of the invasive oyster Crassostrea gigas
      determines its impact on settlement of native oyster larvae.
AB  - Understanding how the density and spatial arrangement of invaders is critical to
      developing management strategies of pest species. The Pacific oyster, Crassostrea
      gigas, has been translocated around the world for aquaculture and in many
      instances has established wild populations. Relative to other species of bivalve,
      it displays rapid suspension feeding, which may cause mortality of pelagic
      invertebrate larvae. We compared the effect on settlement of Sydney rock oyster,
      Saccostrea glomerata, larvae of manipulating the spatial arrangement and density
      of native S. glomerata, and non-native C. gigas. We hypothesized that while
      manipulations of dead oysters would reveal the same positive relationship between
      attachment surface area and S. glomerata settlement between the two species,
      manipulations of live oysters would reveal differing density-dependent effects
      between the native and non-native oyster. In the field, whether oysters were live
      or dead, more larvae settled on C. gigas than S. glomerata when substrate was
      arranged in monospecific clumps. When, however, the two species were
      interspersed, there were no differences in larval settlement between them. By
      contrast, in aquaria simulating a higher effective oyster density, more larvae
      settled on live S. glomerata than C. gigas. When C. gigas was prevented from
      suspension feeding, settlement of larvae on C. gigas was enhanced. By contrast,
      settlement was similar between the two species when dead. While the presently low
      densities of the invasive oyster C. gigas may enhance S. glomerata larval
      settlement in east Australian estuaries, future increases in densities could
      produce negative impacts on native oyster settlement. Synthesis and applications:
      Our study has shown that both the spatial arrangement and density of invaders can
      influence their impact. Hence, management strategies aimed at preventing invasive
      populations reaching damaging sizes should not only consider the threshold
      density at which impacts exceed some acceptable limit, but also how patch
      formation modifies this. 

PMID- 24455121
TI  - An experimental heat wave changes immune defense and life history traits in a
      freshwater snail.
AB  - The predicted increase in frequency and severity of heat waves due to climate
      change is expected to alter disease dynamics by reducing hosts' ability to resist
      infections. This could take place via two different mechanisms: (1) through
      general reduction in hosts' performance under harsh environmental conditions
      and/or (2) through altered resource allocation that reduces expression of defense
      traits in order to maintain other traits. We tested these alternative hypotheses
      by measuring the effect of an experimental heat wave (25 vs. 15 degrees C) on the
      constitutive level of immune defense (hemocyte concentration, phenoloxidase [PO]
      like activity, antibacterial activity of hemolymph), and life history traits
      (growth and number of oviposited eggs) of the great pond snail Lymnaea stagnalis.
      We also manipulated the exposure time to high temperature (1, 3, 5, 7, 9, or 11
      days). We found that if the exposure to high temperature lasted <1 week, immune
      function was not affected. However, when the exposure lasted longer than that,
      the level of snails' immune function (hemocyte concentration and PO-like
      activity) was reduced. Snails' growth and reproduction increased within the first
      week of exposure to high temperature. However, longer exposures did not lead to a
      further increase in cumulative reproductive output. Our results show that short
      experimental heat waves do not alter immune function but lead to plastic
      responses that increase snails' growth and reproduction. Thus, although the
      relative expression of traits changes, short experimental heat waves do not
      impair snails' defenses. Negative effects on performance get pronounced when the
      heat waves are prolonged suggesting that high performance cannot be maintained
      over long time periods. This ultimately reduces the levels of defense traits. 

PMID- 24455122
TI  - Relationship between photosynthetic phosphorus-use efficiency and foliar
      phosphorus fractions in tropical tree species.
AB  - How plants develop adaptive strategies to efficiently use nutrients on infertile
      soils is an important topic in plant ecology. It has been suggested that, with
      decreasing phosphorus (P) availability, plants increase photosynthetic P-use
      efficiency (PPUE) (i.e., the ratio of instantaneous photosynthetic carbon
      assimilation rate per unit foliar P). However, the mechanism to increase PPUE
      remains unclear. In this study, we tested whether high PPUE is explained by an
      optimized allocation of P in cells among P-containing biochemical compounds
      (i.e., foliar P fractions). We investigated the relationships among mass-based
      photosynthetic carbon assimilation rate (A mass), PPUE, total foliar P
      concentration, and foliar P fractions in 10 tree species in two tropical montane
      rain forests with differing soil P availability (five species on sedimentary
      soils and five species on P-poorer ultrabasic serpentine soils) on Mount
      Kinabalu, Borneo. We chemically fractionated foliar P into the following four
      fractions: metabolic P, lipid P, nucleic acid P, and residual P. A mass was
      positively correlated with the concentrations of total foliar P and of metabolic
      P across 10 tree species. Mean A mass and mean concentrations of total foliar P
      and of each foliar P fraction were lower on the P-poorer ultrabasic serpentine
      soils than on the sedimentary soils. There was a negative relationship between
      the proportion of metabolic P per total P and the proportion of lipid P per total
      P. PPUE was positively correlated with the ratio of metabolic P to lipid P. High
      PPUE is explained by the net effect of a relatively greater investment of P into
      P-containing metabolites and a relatively lesser investment into phospholipids in
      addition to generally reduced concentrations of all P fractions. We conclude that
      plants optimize the allocation of P among foliar P fractions for maintaining
      their productivity and growth and for reducing demand for P as their adaptation
      to P-poor soils. 

PMID- 24455123
TI  - Is population structure in the European white stork determined by flyway
      permeability rather than translocation history?
AB  - European white stork are long considered to diverge to eastern and western
      migration pools as a result of independent overwintering flyways. In relatively
      recent times, the western and northern distribution has been subject to dramatic
      population declines and country-specific extirpations. A number of independent
      reintroduction programs were started in the mid 1950s to bring storks back to
      historical ranges. Founder individuals were sourced opportunistically from the
      Eastern and Western European distributions and Algeria, leading to significant
      artificial mixing between eastern and western flyways. Here we use mitochondrial
      and microsatellite DNA to test the contention that prior to translocation,
      eastern and western flyways were genetically distinct. The data show a surprising
      lack of structure at any spatial or temporal scale suggesting that even though
      birds were moved between flyways, there is evidence of natural mixing prior to
      the onset of translocation activities. Overall a high retention of genetic
      diversity, high N ef , and an apparent absence of recent genetic bottleneck
      associated with early 20th century declines suggest that the species is well
      equipped to respond to future environmental pressures. 

PMID- 24455124
TI  - Dynamic occupancy models for analyzing species' range dynamics across large
      geographic scales.
AB  - Large-scale biodiversity data are needed to predict species' responses to global
      change and to address basic questions in macroecology. While such data are
      increasingly becoming available, their analysis is challenging because of the
      typically large heterogeneity in spatial sampling intensity and the need to
      account for observation processes. Two further challenges are accounting for
      spatial effects that are not explained by covariates, and drawing inference on
      dynamics at these large spatial scales. We developed dynamic occupancy models to
      analyze large-scale atlas data. In addition to occupancy, these models estimate
      local colonization and persistence probabilities. We accounted for spatial
      autocorrelation using conditional autoregressive models and autologistic models.
      We fitted the models to detection/nondetection data collected on a quarter-degree
      grid across southern Africa during two atlas projects, using the hadeda ibis
      (Bostrychia hagedash) as an example. The model accurately reproduced the range
      expansion between the first (SABAP1: 1987-1992) and second (SABAP2: 2007-2012)
      Southern African Bird Atlas Project into the drier parts of interior South
      Africa. Grid cells occupied during SABAP1 generally remained occupied, but
      colonization of unoccupied grid cells was strongly dependent on the number of
      occupied grid cells in the neighborhood. The detection probability strongly
      varied across space due to variation in effort, observer identity, seasonality,
      and unexplained spatial effects. We present a flexible hierarchical approach for
      analyzing grid-based atlas data using dynamical occupancy models. Our model is
      similar to a species' distribution model obtained using generalized additive
      models but has a number of advantages. Our model accounts for the heterogeneous
      sampling process, spatial correlation, and perhaps most importantly, allows us to
      examine dynamic aspects of species ranges. 

PMID- 24455125
TI  - Range dynamics, rather than convergent selection, explain the mosaic distribution
      of red-winged blackbird phenotypes.
AB  - Geographic distributions of genetic and phenotypic characters can illuminate
      historical evolutionary processes. In particular, mosaic distributions of
      phenotypically similar populations can arise from parallel evolution or from
      irregular patterns of dispersal and colonization by divergent forms. Two
      phenotypically divergent forms of the red-winged blackbird (Agelaius phoeniceus)
      show a mosaic phenotypic distribution, with a "bicolored" form occurring
      disjunctly in California and Mexico. We analyzed the relationships among these
      bicolored populations and neighboring typical populations, using ~600 bp of
      mitochondrial DNA sequence data and 10 nuclear short tandem repeat loci. We find
      that bicolored populations, although separated by ~3000 km, are genetically more
      similar to one other than they are to typical populations separated by ~400 km.
      We also find evidence of ongoing gene flow among populations, including some
      evidence of asymmetric gene flow. We conclude that the current distribution of
      bicolored forms represents incomplete speciation, where recent asymmetric
      hybridization with typical A. phoeniceus is dividing the range of a formerly
      widespread bicolored form. This hypothesis predicts that bicolored forms may
      suffer extinction by hybridization. Future work will use fine-scaled geographical
      sampling and nuclear sequence data to test for hybrid origins of currently
      typical populations and to more precisely quantify the directionality of gene
      flow. 

PMID- 24455126
TI  - Phylogenetic plant community structure along elevation is lineage specific.
AB  - The trend of closely related taxa to retain similar environmental preferences
      mediated by inherited traits suggests that several patterns observed at the
      community scale originate from longer evolutionary processes. While the effects
      of phylogenetic relatedness have been previously studied within a single genus or
      family, lineage-specific effects on the ecological processes governing community
      assembly have rarely been studied for entire communities or flora. Here, we
      measured how community phylogenetic structure varies across a wide elevation
      gradient for plant lineages represented by 35 families, using a co-occurrence
      index and net relatedness index (NRI). We propose a framework that analyses each
      lineage separately and reveals the trend of ecological assembly at tree nodes. We
      found prevailing phylogenetic clustering for more ancient nodes and
      overdispersion in more recent tree nodes. Closely related species may thus
      rapidly evolve new environmental tolerances to radiate into distinct communities,
      while older lineages likely retain inherent environmental tolerances to occupy
      communities in similar environments, either through efficient dispersal
      mechanisms or the exclusion of older lineages with more divergent environmental
      tolerances. Our study illustrates the importance of disentangling the patterns of
      community assembly among lineages to better interpret the ecological role of
      traits. It also sheds light on studies reporting absence of phylogenetic signal,
      and opens new perspectives on the analysis of niche and trait conservatism across
      lineages. 

PMID- 24455127
TI  - Pattern of inbreeding depression, condition dependence, and additive genetic
      variance in Trinidadian guppy ejaculate traits.
AB  - In polyandrous species, a male's reproductive success depends on his
      fertilization capability and traits enhancing competitive fertilization success
      will be under strong, directional selection. This leads to the prediction that
      these traits should show stronger condition dependence and larger genetic
      variance than other traits subject to weaker or stabilizing selection. While
      empirical evidence of condition dependence in postcopulatory traits is
      increasing, the comparison between sexually selected and 'control' traits is
      often based on untested assumption concerning the different strength of selection
      acting on these traits. Furthermore, information on selection in the past is
      essential, as both condition dependence and genetic variance of a trait are
      likely to be influenced by the pattern of selection acting historically on it.
      Using the guppy (Poecilia reticulata), a livebearing fish with high levels of
      multiple paternity, we performed three independent experiments on three ejaculate
      quality traits, sperm number, velocity, and size, which have been previously
      shown to be subject to strong, intermediate, and weak directional postcopulatory
      selection, respectively. First, we conducted an inbreeding experiment to
      determine the pattern of selection in the past. Second, we used a diet
      restriction experiment to estimate their level of condition dependence. Third, we
      used a half-sib/full-sib mating design to estimate the coefficients of additive
      genetic variance (CVA) underlying these traits. Additionally, using a simulated
      predator evasion test, we showed that both inbreeding and diet restriction
      significantly reduced condition. According to predictions, sperm number showed
      higher inbreeding depression, stronger condition dependence, and larger CVA than
      sperm velocity and sperm size. The lack of significant genetic correlation
      between sperm number and velocity suggests that the former may respond to
      selection independently one from other ejaculate quality traits. Finally, the
      association between sperm number and condition suggests that this trait may
      mediate the genetic benefits of polyandry which have been shown in this species. 

PMID- 24455128
TI  - Multidisciplinary population monitoring when demographic data are sparse: a case
      study of remote trout populations.
AB  - The potential of genetic, genomic, and phenotypic metrics for monitoring
      population trends may be especially high in isolated regions, where traditional
      demographic monitoring is logistically difficult and only sporadic sampling is
      possible. This potential, however, is relatively underexplored empirically. Over
      eleven years, we assessed several such metrics along with traditional ecological
      knowledge and catch data in a socioeconomically important trout species occupying
      a large, remote lake. The data revealed largely stable characteristics in two
      populations over 2-3 generations, but possible contemporary changes in a third
      population. These potential shifts were suggested by reduced catch rates, reduced
      body size, and changes in selection implied at one gene-associated single
      nucleotide polymorphism. A demographic decline in this population, however, was
      ambiguously supported, based on the apparent lack of temporal change in effective
      population size, and corresponding traditional knowledge suggesting little change
      in catch. We illustrate how the pluralistic approach employed has practicality
      for setting future monitoring efforts of these populations, by guiding monitoring
      priorities according to the relative merits of different metrics and availability
      of resources. Our study also considers some advantages and disadvantages to
      adopting a pluralistic approach to population monitoring where demographic data
      are not easily obtained. 

PMID- 24455129
TI  - Ecological speciation in postglacial European whitefish: rapid adaptive
      radiations into the littoral, pelagic, and profundal lake habitats.
AB  - Understanding how a monophyletic lineage of a species diverges into several
      adaptive forms has received increased attention in recent years, but the
      underlying mechanisms in this process are still under debate. Postglacial fishes
      are excellent model organisms for exploring this process, especially the initial
      stages of ecological speciation, as postglacial lakes represent replicated
      discrete environments with variation in available niches. Here, we combine data
      of niche utilization, trophic morphology, and 17 microsatellite loci to
      investigate the diversification process of three sympatric European whitefish
      morphs from three northern Fennoscandian lakes. The morphological divergence in
      the gill raker number among the whitefish morphs was related to the utilization
      of different trophic niches and was associated with reproductive isolation within
      and across lakes. The intralacustrine comparison of whitefish morphs showed that
      these systems represent two levels of adaptive divergence: (1) a consistent
      littoral-pelagic resource axis; and (2) a more variable littoral-profundal
      resource axis. The results also indicate that the profundal whitefish morph has
      diverged repeatedly from the ancestral littoral whitefish morph in sympatry in
      two different watercourses. In contrast, all the analyses performed revealed
      clustering of the pelagic whitefish morphs across lakes suggesting parallel
      postglacial immigration with the littoral whitefish morph into each lake.
      Finally, the analyses strongly suggested that the trophic adaptive trait, number
      of gill rakers, was under diversifying selection in the different whitefish
      morphs. Together, the results support a complex evolutionary scenario where
      ecological speciation acts, but where both allopatric (colonization history) and
      sympatric (within watercourse divergence) processes are involved. 

PMID- 24455130
TI  - Sneaker "jack" males outcompete dominant "hooknose" males under sperm competition
      in Chinook salmon (Oncorhynchus tshawytscha).
AB  - In a variety of taxa, males deploy alternative reproductive tactics to secure
      fertilizations. In many species, small "sneaker" males attempt to steal
      fertilizations while avoiding encounters with larger, more aggressive, dominant
      males. Sneaker males usually face a number of disadvantages, including reduced
      access to females and the higher likelihood that upon ejaculation, their sperm
      face competition from other males. Nevertheless, sneaker males represent an
      evolutionarily stable strategy under a wide range of conditions. Game theory
      suggests that sneaker males compensate for these disadvantages by investing
      disproportionately in spermatogenesis, by producing more sperm per unit body mass
      (the "fair raffle") and/or by producing higher quality sperm (the "loaded
      raffle"). Here, we test these models by competing sperm from sneaker "jack" males
      against sperm from dominant "hooknose" males in Chinook salmon. Using two
      complementary approaches, we reject the fair raffle in favor of the loaded raffle
      and estimate that jack males were ~1.35 times as likely as hooknose males to
      fertilize eggs under controlled competitive conditions. Interestingly, the
      direction and magnitude of this skew in paternity shifted according to individual
      female egg donors, suggesting cryptic female choice could moderate the outcomes
      of sperm competition in this externally fertilizing species. 

PMID- 24455131
TI  - Evaluating the carbon balance estimate from an automated ground-level flux
      chamber system in artificial grass mesocosms.
AB  - Measuring and modeling carbon (C) stock changes in terrestrial ecosystems are
      pivotal in addressing global C-cycling model uncertainties. Difficulties in
      detecting small short-term changes in relatively large C stocks require the
      development of robust sensitive flux measurement techniques. Net ecosystem
      exchange (NEE) ground-level chambers are increasingly used to assess C dynamics
      in low vegetation ecosystems but, to date, have lacked formal rigorous field
      validation against measured C stock changes. We developed and deployed an
      automated and multiplexed C-flux chamber system in grassland mesocosms in order
      rigorously to compare ecosystem total C budget obtained using hourly C-flux
      measurements versus destructive net C balance. The system combines transparent
      NEE and opaque respiration chambers enabling partitioning of photosynthetic and
      respiratory fluxes. The C-balance comparison showed good agreement between the
      two methods, but only after NEE fluxes were corrected for light reductions due to
      chamber presence. The dark chamber fluxes allowed assessing temperature
      sensitivity of ecosystem respiration (R eco) components (i.e., heterotrophic vs.
      autotrophic) at different growth stages. We propose that such automated flux
      chamber systems can provide an accurate C balance, also enabling pivotal
      partitioning of the different C-flux components (e.g., photosynthesis and
      respiration) suitable for model evaluation and developments. 

PMID- 24455132
TI  - Eucalypts face increasing climate stress.
AB  - Global climate change is already impacting species and ecosystems across the
      planet. Trees, although long-lived, are sensitive to changes in climate,
      including climate extremes. Shifts in tree species' distributions will influence
      biodiversity and ecosystem function at scales ranging from local to landscape;
      dry and hot regions will be especially vulnerable. The Australian continent has
      been especially susceptible to climate change with extreme heat waves, droughts,
      and flooding in recent years, and this climate trajectory is expected to
      continue. We sought to understand how climate change may impact Australian
      ecosystems by modeling distributional changes in eucalypt species, which dominate
      or codominate most forested ecosystems across Australia. We modeled a
      representative sample of Eucalyptus and Corymbia species (n = 108, or 14% of all
      species) using newly available Representative Concentration Pathway (RCP)
      scenarios developed for the 5th Assessment Report of the IPCC, and bioclimatic
      and substrate predictor variables. We compared current, 2025, 2055, and 2085
      distributions. Overall, Eucalyptus and Corymbia species in the central desert and
      open woodland regions will be the most affected, losing 20% of their climate
      space under the mid-range climate scenario and twice that under the extreme
      scenario. The least affected species, in eastern Australia, are likely to lose
      10% of their climate space under the mid-range climate scenario and twice that
      under the extreme scenario. Range shifts will be lateral as well as polewards,
      and these east-west transitions will be more significant, reflecting the strong
      influence of precipitation rather than temperature changes in subtropical and
      midlatitudes. These net losses, and the direction of shifts and contractions in
      range, suggest that many species in the eastern and southern seaboards will be
      pushed toward the continental limit and that large tracts of currently treed
      landscapes, especially in the continental interior, will change dramatically in
      terms of species composition and ecosystem structure. 

PMID- 24455133
TI  - Integrating batch marks and radio tags to estimate the size of a closed
      population with a movement model.
AB  - Movement models require individually identifiable marks to estimate the movement
      rates among strata. But they are relatively expensive to apply and monitor. Batch
      marks can be readily applied, but individual animal movements cannot be
      identified. We describe a method to estimate population size in a stratified
      population when movement takes place among strata and animals are marked with a
      combination of batch and individually identifiable tags. A hierarchical model
      with Bayesian inference is developed that pools information across segments on
      the detection efficiency based on radio-tagged fish and also uses the movement of
      the radio-tagged fish to impute the movement of the batch-marked fish to provide
      estimates of the population size on a segment and river level. The batch marks
      provide important information to help estimate the movement rates, but contribute
      little to the overall estimate of the population size. In this case, the
      approximate equal catchability among strata in either sample obviates the need
      for stratification. 

PMID- 24455134
TI  - Intraspecific phenotypic variation in a fish predator affects multitrophic lake
      metacommunity structure.
AB  - Contemporary insights from evolutionary ecology suggest that population
      divergence in ecologically important traits within predators can generate
      diversifying ecological selection on local community structure. Many studies
      acknowledging these effects of intraspecific variation assume that local
      populations are situated in communities that are unconnected to similar
      communities within a shared region. Recent work from metacommunity ecology
      suggests that species dispersal among communities can also influence species
      diversity and composition but can depend upon the relative importance of the
      local environment. Here, we study the relative effects of intraspecific
      phenotypic variation in a fish predator and spatial processes related to plankton
      species dispersal on multitrophic lake plankton metacommunity structure.
      Intraspecific diversification in foraging traits and residence time of the
      planktivorous fish alewife (Alosa pseudoharengus) among coastal lakes yields lake
      metacommunities supporting three lake types which differ in the phenotype and
      incidence of alewife: lakes with anadromous, landlocked, or no alewives. In
      coastal lakes, plankton community composition was attributed to dispersal versus
      local environmental predictors, including intraspecific variation in alewives.
      Local and beta diversity of zooplankton and phytoplankton was additionally
      measured in response to intraspecific variation in alewives. Zooplankton
      communities were structured by species sorting, with a strong influence of
      intraspecific variation in A. pseudoharengus. Intraspecific variation altered
      zooplankton species richness and beta diversity, where lake communities with
      landlocked alewives exhibited intermediate richness between lakes with anadromous
      alewives and without alewives, and greater community similarity. Phytoplankton
      diversity, in contrast, was highest in lakes with landlocked alewives. The
      results indicate that plankton dispersal in the region supplied a migrant pool
      that was strongly structured by intraspecific variation in alewives. This is one
      of the first studies to demonstrate that intraspecific phenotypic variation in a
      predator can maintain contrasting patterns of multitrophic diversity in
      metacommunities. 

PMID- 24455135
TI  - Changes in the temperature sensitivity of SOM decomposition with grassland
      succession: implications for soil C sequestration.
AB  - Understanding the temperature sensitivity (Q 10) of soil organic matter (SOM)
      decomposition is important for predicting soil carbon (C) sequestration in
      terrestrial ecosystems under warming scenarios. Whether Q 10 varies predictably
      with ecosystem succession and the ways in which the stoichiometry of input SOM
      influences Q 10 remain largely unknown. We investigate these issues using a
      grassland succession series from free-grazing to 31-year grazing-exclusion
      grasslands in Inner Mongolia, and an incubation experiment performed at six
      temperatures (0, 5, 10, 15, 20, and 25 degrees C) and with four substrates:
      control (CK), glucose (GLU), mixed grass leaf (GRA), and Medicago falcata leaf
      (MED). The results showed that basal soil respiration (20 degrees C) and
      microbial biomass C (MBC) logarithmically decreased with grassland succession. Q
      10 decreased logarithmically from 1.43 in free-grazing grasslands to 1.22 in 31
      year grazing-exclusion grasslands. Q 10 increased significantly with the addition
      of substrates, and the Q 10 levels increased with increase in N:C ratios of
      substrate. Moreover, accumulated C mineralization was controlled by the N:C ratio
      of newly input SOM and by incubation temperature. Changes in Q 10 with grassland
      ecosystem succession are controlled by the stoichiometry of newly input SOM, MBC,
      and SOM quality, and the combined effects of which could partially explain the
      mechanisms underlying soil C sequestration in the long-term grazing-exclusion
      grasslands in Inner Mongolia, China. The findings highlight the effect of
      substrate stoichiometry on Q 10 which requires further study. 

PMID- 24455136
TI  - Embryonic response to long-term exposure of the marine crustacean Nephrops
      norvegicus to ocean acidification and elevated temperature.
AB  - Due to anthropogenic CO2 emissions, our oceans have gradually become warmer and
      more acidic. To better understand the consequences of this, there is a need for
      long-term (months) and multistressor experiments. Earlier research demonstrates
      that the effects of global climate change are specific to species and life
      stages. We exposed berried Norway lobsters (Nephrops norvegicus), during 4 months
      to the combination of six ecologically relevant temperatures (5-18 degrees C) and
      reduced pH (by 0.4 units). Embryonic responses were investigated by quantifying
      proxies for development rate and fitness including: % yolk consumption, mean
      heart rate, rate of oxygen consumption, and oxidative stress. We found no
      interactions between temperature and pH, and reduced pH only affected the level
      of oxidative stress significantly, with a higher level of oxidative stress in the
      controls. Increased temperature and % yolk consumed had positive effects on all
      parameters except on oxidative stress, which did not change in response to
      temperature. There was a difference in development rate between the ranges of 5
      10 degrees C (Q 10: 5.4) and 10-18 degrees C (Q 10: 2.9), implicating a thermal
      break point at 10 degrees C or below. No thermal limit to a further increased
      development rate was found. The insensitivity of N. norvegicus embryos to low pH
      might be explained by adaptation to a pH-reduced external habitat and/or internal
      hypercapnia during incubation. Our results thus indicate that this species would
      benefit from global warming and be able to withstand the predicted decrease in
      ocean pH in the next century during their earliest life stages. However, future
      studies need to combine low pH and elevated temperature treatments with hypoxia
      as hypoxic events are frequently and increasingly occurring in the habitat of
      benthic species. 

PMID- 24455137
TI  - Incest versus abstinence: reproductive trade-offs between mate limitation and
      progeny fitness in a self-incompatible invasive plant.
AB  - Plant mating systems represent an evolutionary and ecological trade-off between
      reproductive assurance through selfing and maximizing progeny fitness through
      outbreeding. However, many plants with sporophytic self-incompatibility systems
      exhibit dominance interactions at the S-locus that allow biparental inbreeding,
      thereby facilitating mating between individuals that share alleles at the S
      locus. We investigated this trade-off by estimating mate availability and
      biparental inbreeding depression in wild radish from five different populations
      across Australia. We found dominance interactions among S-alleles increased mate
      availability relative to estimates based on individuals that did not share S
      alleles. Twelve of the sixteen fitness variables were significantly reduced by
      inbreeding. For all the three life-history phases evaluated, self-fertilized
      offspring suffered a greater than 50% reduction in fitness, while full-sib and
      half-sib offspring suffered a less than 50% reduction in fitness. Theory
      indicates that fitness costs greater than 50% can result in an evolutionary
      trajectory toward a stable state of self-incompatibility (SI). This study
      suggests that dominance interactions at the S-locus provide a possible third
      stable state between SI and SC where biparental inbreeding increases mate
      availability with relatively minor fitness costs. This strategy allows weeds to
      establish in new environments while maintaining a functional SI system. 

PMID- 24455138
TI  - Climate change and fire effects on a prairie-woodland ecotone: projecting species
      range shifts with a dynamic global vegetation model.
AB  - Large shifts in species ranges have been predicted under future climate scenarios
      based primarily on niche-based species distribution models. However, the
      mechanisms that would cause such shifts are uncertain. Natural and anthropogenic
      fires have shaped the distributions of many plant species, but their effects have
      seldom been included in future projections of species ranges. Here, we examine
      how the combination of climate and fire influence historical and future
      distributions of the ponderosa pine-prairie ecotone at the edge of the Black
      Hills in South Dakota, USA, as simulated by MC1, a dynamic global vegetation
      model that includes the effects of fire, climate, and atmospheric CO2
      concentration on vegetation dynamics. For this purpose, we parameterized MC1 for
      ponderosa pine in the Black Hills, designating the revised model as MC1-WCNP.
      Results show that fire frequency, as affected by humidity and temperature, is
      central to the simulation of historical prairies in the warmer lowlands versus
      woodlands in the cooler, moister highlands. Based on three downscaled general
      circulation model climate projections for the 21st century, we simulate greater
      frequencies of natural fire throughout the area due to substantial warming and,
      for two of the climate projections, lower relative humidity. However, established
      ponderosa pine forests are relatively fire resistant, and areas that were
      initially wooded remained so over the 21st century for most of our future climate
      x fire management scenarios. This result contrasts with projections for ponderosa
      pine based on climatic niches, which suggest that its suitable habitat in the
      Black Hills will be greatly diminished by the middle of the 21st century. We
      hypothesize that the differences between the future predictions from these two
      approaches are due in part to the inclusion of fire effects in MC1, and we
      highlight the importance of accounting for fire as managed by humans in assessing
      both historical species distributions and future climate change effects. 

PMID- 24455139
TI  - Phenotypic divergence in reproductive traits of a moth population experiencing a
      phenological shift.
AB  - Allochrony that is reproductive isolation by time may further lead to divergence
      of reproductive adaptive traits in response to different environmental pressures
      over time. A unique "summer" population of the pine processionary moth
      Thaumetopoea pityocampa, reproductively isolated from the typical winter
      populations by allochronic differentiation, is here analyzed. This
      allochronically shifted population reproduces in the spring and develops in the
      summer, whereas "winter" populations reproduce in the late summer and have winter
      larval development. Both summer and winter populations coexist in the same pine
      stands, yet they face different climatic pressures as their active stages are
      present in different seasons. The occurrence of significant differences between
      the reproductive traits of the summer population and the typical winter
      populations (either sympatric or allopatric) is thus hypothesized. Female
      fecundity, egg size, egg covering, and egg parasitism were analyzed showing that
      the egg load was lower and that egg size was higher in the summer population than
      in all the studied winter populations. The scales that cover the egg batches of
      T. pityocampa differed significantly between populations in shape and color,
      resulting in a looser and darker covering in the summer population. The single
      specialist egg parasitoid species of this moth was almost missing in the summer
      population, and the overall parasitism rates were lower than in the winter
      population. Results suggest the occurrence of phenotypic differentiation between
      the summer population and the typical T. pityocampa winter populations for the
      life-history traits studied. This work provides an insight into how ecological
      divergence may follow the process of allochronic reproductive isolation. 

PMID- 24455140
TI  - Can invasions occur without change? A comparison of G-matrices and selection in
      the peach-potato aphid, Myzus persicae.
AB  - Most evolutionary research on biological invasions has focused on changes seen
      between the native and invaded range for a particular species. However, it is
      likely that species that live in human-modified habitats in their native range
      might have evolved specific adaptations to those environments, which increase the
      likelihood of establishment and spread in similar human-altered environments.
      From a quantitative genetic perspective, this hypothesis suggests that both
      native and introduced populations should reside at or near the same adaptive
      peak. Therefore, we should observe no overall changes in the G (genetic variance
      covariance) matrices between native and introduced ranges, and stabilizing
      selection on fitness-related traits in all populations. We tested these
      predictions comparing three populations of the worldwide pest Myzus persicae from
      the Middle East (native range) and the UK and Chile (separately introduced
      ranges). In general, our results provide mixed support for this idea, but further
      comparisons of other species are needed. In particular, we found that there has
      been some limited evolution in the studied traits, with the Middle East
      population differing from the UK and Chilean populations. This was reflected in
      the structure of the G-matrices, in which Chile differed from both UK and Middle
      East populations. Furthermore, the amount of genetic variation was massively
      reduced in Chile in comparison with UK and Middle East populations. Finally, we
      found no detectable selection on any trait in the three populations, but clones
      from the introduced ranges started to reproduce later, were smaller, had smaller
      offspring, and had lower reproductive fitness than clones from the native range. 

PMID- 24455141
TI  - A shared mechanism of defense against predators and parasites: chitin regulation
      and its implications for life-history theory.
AB  - Defenses against predators and parasites offer excellent illustrations of
      adaptive phenotypic plasticity. Despite vast knowledge about such induced
      defenses, they have been studied largely in isolation, which is surprising, given
      that predation and parasitism are ubiquitous and act simultaneously in the wild.
      This raises the possibility that victims must trade-off responses to predation
      versus parasitism. Here, we propose that arthropod responses to predators and
      parasites will commonly be based on the endocrine regulation of chitin synthesis
      and degradation. The proposal is compelling because many inducible defenses are
      centered on temporal or spatial modifications of chitin-rich structures.
      Moreover, we show how the chitin synthesis pathway ends in a split to carapace or
      gut chitin, and how this form of molecular regulation can be incorporated into
      theory on life-history trade-offs, specifically the Y-model. Our hypothesis thus
      spans several biological scales to address advice from Stearns that "Endocrine
      mechanisms may prove to be only the tip of an iceberg of physiological mechanisms
      that modulate the expression of genetic covariance". 

PMID- 24455143
TI  - The evolution of birdsong on islands.
AB  - Islands are simplified, isolated ecosystems, providing an ideal set-up to study
      evolution. Among several traits that are expected to change on islands, an
      interesting but poorly understood example concerns signals used in animal
      communication. Islands are typified by reduced species diversity, increased
      population density, and reduced mate competition, all of which could affect
      communication signals. We used birdsong to investigate whether there are
      systematic changes in communication signals on islands, by undertaking a broad
      comparison based on pairs of closely related island-mainland species across the
      globe. We studied song traits related to complexity (number of different
      syllables, frequency bandwidth), to vocal performance (syllable delivery rate,
      song duration), and also three particular song elements (rattles, buzzes, and
      trills) generally implicated in aggressive communication. We also investigated
      whether song complexity was related to the number of similar sympatric species.
      We found that island species were less likely to produce broadband and likely
      aggressive song elements (rattles and buzzes). By contrast, various aspects of
      song complexity and performance did not differ between island and mainland
      species. Species with fewer same-family sympatric species used wider frequency
      bandwidths, as predicted by the character release hypothesis, both on continents
      and on islands. Our study supports the hypothesis of a reduction in aggressive
      behavior on islands and suggests that discrimination against closely related
      species is an important factor influencing birdsong evolution. 

PMID- 24455144
TI  - Life history of the Glanville fritillary butterfly in fragmented versus
      continuous landscapes.
AB  - Habitat loss and fragmentation threaten the long-term viability of innumerable
      species of plants and animals. At the same time, habitat fragmentation may impose
      strong natural selection and lead to evolution of life histories with possible
      consequences for demographic dynamics. The Baltic populations of the Glanville
      fritillary butterfly (Melitaea cinxia) inhabit regions with highly fragmented
      habitat (networks of small dry meadows) as well as regions with extensive
      continuous habitat (calcareous alvar grasslands). Here, we report the results of
      common garden studies on butterflies originating from two highly fragmented
      landscapes (FL) in Finland and Sweden and from two continuous landscapes (CL) in
      Sweden and Estonia, conducted in a large outdoor cage (32 by 26 m) and in the
      laboratory. We investigated a comprehensive set of 51 life-history traits,
      including measures of larval growth and development, flight performance, and
      adult reproductive behavior. Seventeen of the 51 traits showed a significant
      difference between fragmented versus CL. Most notably, the growth rate of
      postdiapause larvae and several measures of flight capacity, including flight
      metabolic rate, were higher in butterflies from fragmented than CL. Females from
      CL had shorter intervals between consecutive egg clutches and somewhat higher
      life-time egg production, but shorter longevity, than females from FL. These
      results are likely to reflect the constant opportunities for oviposition in
      females living in continuous habitats, while the more dispersive females from FL
      allocate more resources to dispersal capacity at the cost of egg maturation rate.
      This study supports theoretical predictions about small population sizes and high
      rate of population turnover in fragmented habitats selecting for increased rate
      of dispersal, but the results also indicate that many other life-history traits
      apart from dispersal are affected by the degree of habitat fragmentation. 

PMID- 24455145
TI  - Antiparasite treatments reduce humoral immunity and impact oxidative status in
      raptor nestlings.
AB  - Parasites are natural stressors that may have multiple negative effects on their
      host as they usurp energy and nutrients and may lead to costly immune responses
      that may cause oxidative stress. At early stages, animals may be more sensitive
      to infectious organisms because of their rapid growth and partly immature immune
      system. The objective of this study was to explore effects of parasites by
      treating chicks of two raptor species (northern goshawk Accipiter gentilis and
      white-tailed sea eagle Haliaeetus albicilla) against both endoparasites (internal
      parasites) and ectoparasites (external parasites). Nests were either treated
      against ectoparasites by spraying with pyrethrin or left unsprayed as control
      nests. Within each nest, chicks were randomly orally treated with either an
      antihelminthic medication (fenbendazole) or sterile water as control treatment.
      We investigated treatment effects on plasma (1) total antioxidant capacity TAC
      (an index of nonenzymatic circulating antioxidant defenses), (2) total oxidant
      status TOS (a measure of plasmatic oxidants), and (3) immunoglobulin levels (a
      measure of humoral immune function). Treatment against ectoparasites led to a
      reduction in circulating immunoglobulin plasma levels in male chicks. TOS was
      higher when not receiving any parasite reduction treatment and when receiving
      both endo- and ectoparasitic reduction treatment compared with receiving only one
      treatment. TAC was higher in all treatment groups, when compared to controls.
      Despite the relatively low sample size, this experimental study suggests complex
      but similar relationships between treatment groups and oxidative status and
      immunoglobulin levels in two raptor species. 

PMID- 24455146
TI  - Deceptive single-locus taxonomy and phylogeography: Wolbachia-associated
      divergence in mitochondrial DNA is not reflected in morphology and nuclear
      markers in a butterfly species.
AB  - The satyrine butterfly Coenonympha tullia (Nymphalidae: Satyrinae) displays a
      deep split between two mitochondrial clades, one restricted to northern Alberta,
      Canada, and the other found throughout Alberta and across North America. We
      confirm this deep divide and test hypotheses explaining its phylogeographic
      structure. Neither genitalia morphology nor nuclear gene sequence supports
      cryptic species as an explanation, instead indicating differences between nuclear
      and mitochondrial genome histories. Sex-biased dispersal is unlikely to cause
      such mito-nuclear differences; however, selective sweeps by reproductive
      parasites could have led to this conflict. About half of the tested samples were
      infected by Wolbachia bacteria. Using multilocus strain typing for three
      Wolbachia genes, we show that the divergent mitochondrial clades are associated
      with two different Wolbachia strains, supporting the hypothesis that the mito
      nuclear differences resulted from selection on the mitochondrial genome due to
      selective sweeps by Wolbachia strains. 

PMID- 24455147
TI  - Long-term fertilization of a boreal Norway spruce forest increases the
      temperature sensitivity of soil organic carbon mineralization.
AB  - Boreal ecosystems store one-third of global soil organic carbon (SOC) and are
      particularly sensitive to climate warming and higher nutrient inputs. Thus, a
      better description of how forest managements such as nutrient fertilization
      impact soil carbon (C) and its temperature sensitivity is needed to better
      predict feedbacks between C cycling and climate. The temperature sensitivity of
      in situ soil C respiration was investigated in a boreal forest, which has
      received long-term nutrient fertilization (22 years), and compared with the
      temperature sensitivity of C mineralization measured in the laboratory. We found
      that the fertilization treatment increased both the response of soil in situ CO2
      effluxes to a warming treatment and the temperature sensitivity of C
      mineralization measured in the laboratory (Q10). These results suggested that
      soil C may be more sensitive to an increase in temperature in long-term
      fertilized in comparison with nutrient poor boreal ecosystems. Furthermore, the
      fertilization treatment modified the SOC content and the microbial community
      composition, but we found no direct relationship between either SOC or microbial
      changes and the temperature sensitivity of C mineralization. However, the
      relation between the soil C:N ratio and the fungal/bacterial ratio was changed in
      the combined warmed and fertilized treatment compared with the other treatments,
      which suggest that strong interaction mechanisms may occur between nutrient input
      and warming in boreal soils. Further research is needed to unravel into more
      details in how far soil organic matter and microbial community composition
      changes are responsible for the change in the temperature sensitivity of soil C
      under increasing mineral N inputs. Such research would help to take into account
      the effect of fertilization managements on soil C storage in C cycling numerical
      models. 

PMID- 24455148
TI  - Underestimating the frequency, strength and cost of antipredator responses with
      data from GPS collars: an example with wolves and elk.
AB  - Field studies that rely on fixes from GPS-collared predators to identify
      encounters with prey will often underestimate the frequency and strength of
      antipredator responses. These underestimation biases have several mechanistic
      causes. (1) Step bias: The distance between successive GPS fixes can be large,
      and encounters that occur during these intervals go undetected. This bias will
      generally be strongest for cursorial hunters that can rapidly cover large
      distances (e.g., wolves and African wild dogs) and when the interval between GPS
      fixes is long relative to the duration of a hunt. Step bias is amplified as the
      path travelled between successive GPS fixes deviates from a straight line. (2)
      Scatter bias: Only a small fraction of the predators in a population typically
      carry GPS collars, and prey encounters with uncollared predators go undetected
      unless a collared group-mate is present. This bias will generally be stronger for
      fission-fusion hunters (e.g., spotted hyenas, wolves, and lions) than for highly
      cohesive hunters (e.g., African wild dogs), particularly when their group sizes
      are large. Step bias and scatter bias both cause underestimation of the frequency
      of antipredator responses. (3) Strength bias: Observations of prey in the absence
      of GPS fix from a collared predator will generally include a mixture of cases in
      which predators were truly absent and cases in which predators were present but
      not detected, which causes underestimation of the strength of antipredator
      responses. We quantified these biases with data from wolves and African wild dogs
      and found that fixes from GPS collars at 3-h intervals underestimated the
      frequency and strength of antipredator responses by a factor >10. We reexamined
      the results of a recent study of the nonconsumptive effects of wolves on elk in
      light of these results and confirmed that predation risk has strong effects on
      elk dynamics by reducing the pregnancy rate. 

PMID- 24455149
TI  - Interactions between assembly order and temperature can alter both short- and
      long-term community composition.
AB  - Both the order in which species arrive in a community, and environmental
      conditions, such as temperature, are known to affect community structure. Little
      is known, however, about the potential for, and occurrence of, interactions
      between assembly history and the environment. Of particular, interest may be the
      interaction between temperature and community assembly dynamics, especially in
      the light of predicted global climatic change and the fundamental processes that
      are governed, through metabolic rate, by an individual's environmental
      temperature. We present, to our knowledge, the first experimental exploration of
      how the influence of assembly history, temperature, and the interaction between
      the two alters the structure of communities of competitors, using small-scale
      protist microcosm communities where temperature and assembly order were
      manipulated factorially. In our experiment, the most important driver of long
      term abundance was temperature but long-lasting assembly order effects influenced
      the relationship between temperature and abundance. Any advantage of early
      colonization proved to be short-lived, and there was rarely any long-term
      advantage to colonizing a habitat before other species. The results presented
      here suggest that environmental conditions shape community composition, but that
      occasionally temperature could interact with the stochastic nature of community
      assembly to significantly alter future community composition, especially where
      temperature change has been large. This could have important implications for the
      dynamics of both rare and invasive species. 

PMID- 24455150
TI  - Natural variation in chemosensation: lessons from an island nematode.
AB  - All organisms must interact with their environment, responding in behavioral,
      chemical, and other ways to various stimuli throughout their life cycles.
      Characterizing traits that directly represent an organism's ability to sense and
      react to their environment provides useful insight into the evolution of life
      history strategies. One such trait for the nematode Pristionchus pacificus,
      chemosensation, is involved in navigation to beetle hosts. Essential for the
      survival of the nematode, chemosensory behavior may be subject to variation as
      nematodes discriminate among chemical cues to complete their life cycle. We
      examine this hypothesis using natural isolates of P. pacificus from La Reunion
      Island. We select strains from a variety of La Reunion beetle hosts and
      geographic locations and examine their chemoattraction response toward organic
      compounds, beetle washes, and live beetles. We find that nematodes show
      significant differences in their response to various chemicals and are able to
      chemotax to live beetles in a novel assay. Further, strains can discriminate
      among different cues, showing more similar responses toward beetle washes than to
      organic compounds in cluster analyses. However, we find that variance in
      chemoattraction response is not significantly associated with temperature,
      location, or beetle host. Rather, strains show a more concerted response toward
      compounds they most likely directly encounter in the wild. We suggest that
      divergence in odor-guided behavior in P. pacificus may therefore have an
      important ecological component. 

PMID- 24455151
TI  - Nondetection sampling bias in marked presence-only data.
AB  - Species distribution models (SDM) are tools used to determine environmental
      features that influence the geographic distribution of species' abundance and
      have been used to analyze presence-only records. Analysis of presence-only
      records may require correction for nondetection sampling bias to yield reliable
      conclusions. In addition, individuals of some species of animals may be highly
      aggregated and standard SDMs ignore environmental features that may influence
      aggregation behavior.We contend that nondetection sampling bias can be treated as
      missing data. Statistical theory and corrective methods are well developed for
      missing data, but have been ignored in the literature on SDMs. We developed a
      marked inhomogeneous Poisson point process model that accounted for nondetection
      and aggregation behavior in animals and tested our methods on simulated
      data.Correcting for nondetection sampling bias requires estimates of the
      probability of detection which must be obtained from auxiliary data, as presence
      only data do not contain information about the detection mechanism. Weighted
      likelihood methods can be used to correct for nondetection if estimates of the
      probability of detection are available. We used an inhomogeneous Poisson point
      process model to model group abundance, a zero-truncated generalized linear model
      to model group size, and combined these two models to describe the distribution
      of abundance. Our methods performed well on simulated data when nondetection was
      accounted for and poorly when detection was ignored.We recommend researchers
      consider the effects of nondetection sampling bias when modeling species
      distributions using presence-only data. If information about the detection
      process is available, we recommend researchers explore the effects of
      nondetection and, when warranted, correct the bias using our methods. We
      developed our methods to analyze opportunistic presence-only records of whooping
      cranes (Grus americana), but expect that our methods will be useful to ecologists
      analyzing opportunistic presence-only records of other species of animals. 

PMID- 24455152
TI  - Invasion biology in non-free-living species: interactions between abiotic
      (climatic) and biotic (host availability) factors in geographical space in
      crayfish commensals (Ostracoda, Entocytheridae).
AB  - In invasion processes, both abiotic and biotic factors are considered essential,
      but the latter are usually disregarded when modeling the potential spread of
      exotic species. In the framework of set theory, interactions between biotic (B),
      abiotic (A), and movement-related (M) factors in the geographical space can be
      hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to
      estimate A and B areas. The main aim of our survey was to evaluate the
      interactions between abiotic (climatic) and biotic (host availability) factors in
      geographical space for exotic symbionts (i.e., non-free-living species), using
      ENM techniques combined with a BAM framework and using exotic Entocytheridae
      (Ostracoda) found in Europe as model organisms. We carried out an extensive
      survey to evaluate the distribution of entocytherids hosted by crayfish in Europe
      by checking 94 European localities and 12 crayfish species. Both exotic
      entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis,
      were widely distributed in W Europe living on the exotic crayfish species
      Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids
      were observed in the remaining crayfish species. The suitable area for A. sinuosa
      was mainly restricted by its own limitations to minimum temperatures in W and N
      Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere
      occidentalis was mostly restricted by host availability in circum-Mediterranean
      regions due to limitations of P. leniusculus to higher precipitation seasonality
      and maximum temperatures. The combination of ENMs with set theory allows studying
      the invasive biology of symbionts and provides clues about biogeographic barriers
      due to abiotic or biotic factors limiting the expansion of the symbiont in
      different regions of the invasive range. The relative importance of abiotic and
      biotic factors on geographical space can then be assessed and applied in
      conservation plans. This approach can also be implemented in other systems where
      the target species is closely interacting with other taxa. 

PMID- 24455153
TI  - Soil pathogen communities associated with native and non-native Phragmites
      australis populations in freshwater wetlands.
AB  - Soil pathogens are believed to be major contributors to negative plant-soil
      feedbacks that regulate plant community dynamics and plant invasions. While the
      theoretical basis for pathogen regulation of plant communities is well
      established within the plant-soil feedback framework, direct experimental
      evidence for pathogen community responses to plants has been limited, often
      relying largely on indirect evidence based on above-ground plant responses. As a
      result, specific soil pathogen responses accompanying above-ground plant
      community dynamics are largely unknown. Here, we examine the oomycete pathogens
      in soils conditioned by established populations of native noninvasive and non
      native invasive haplotypes of Phragmites australis (European common reed). Our
      aim was to assess whether populations of invasive plants harbor unique
      communities of pathogens that differ from those associated with noninvasive
      populations and whether the distribution of taxa within these communities may
      help to explain invasive success. We compared the composition and abundance of
      pathogenic and saprobic oomycete species over a 2-year period. Despite a
      diversity of oomycete taxa detected in soils from both native and non-native
      populations, pathogen communities from both invaded and noninvaded soils were
      dominated by species of Pythium. Pathogen species that contributed the most to
      the differences observed between invaded and noninvaded soils were distributed
      between invaded and noninvaded soils. However, the specific taxa in invaded soils
      responsible for community differences were distinct from those in noninvaded
      soils that contributed to community differences. Our results indicate that,
      despite the phylogenetic relatedness of native and non-native P. australis
      haplotypes, pathogen communities associated with the dominant non-native
      haplotype are distinct from those of the rare native haplotype. Pathogen taxa
      that dominate either noninvaded or invaded soils suggest different potential
      mechanisms of invasion facilitation. These findings are consistent with the
      hypothesis that non-native plant species that dominate landscapes may "cultivate"
      a different soil pathogen community to their rhizosphere than those of rarer
      native species. 

PMID- 24455154
TI  - Smartphones in ecology and evolution: a guide for the app-rehensive.
AB  - Smartphones and their apps (application software) are now used by millions of
      people worldwide and represent a powerful combination of sensors, information
      transfer, and computing power that deserves better exploitation by ecological and
      evolutionary researchers. We outline the development process for research apps,
      provide contrasting case studies for two new research apps, and scan the research
      horizon to suggest how apps can contribute to the rapid collection,
      interpretation, and dissemination of data in ecology and evolutionary biology. We
      emphasize that the usefulness of an app relies heavily on the development
      process, recommend that app developers are engaged with the process at the
      earliest possible stage, and commend efforts to create open-source software
      scaffolds on which customized apps can be built by nonexperts. We conclude that
      smartphones and their apps could replace many traditional handheld sensors,
      calculators, and data storage devices in ecological and evolutionary research. We
      identify their potential use in the high-throughput collection, analysis, and
      storage of complex ecological information. 

PMID- 24455156
TI  - Divergence of feeding channels within the soil food web determined by ecosystem
      type.
AB  - Understanding trophic linkages within the soil food web (SFW) is hampered by its
      opacity, diversity, and limited niche adaptation. We need to expand our insight
      between the feeding guilds of fauna and not just count biodiversity. The soil
      fauna drive nutrient cycling and play a pivotal, but little understood role
      within both the carbon (C) and nitrogen (N) cycles that may be ecosystem
      dependent. Here, we define the structure of the SFW in two habitats (grassland
      and woodland) on the same soil type and test the hypothesis that land management
      would alter the SFW in these habitats. To do this, we census the community
      structure and use stable isotope analysis to establish the pathway of C and N
      through each trophic level within the ecosystems. Stable isotope ratios of C and
      N from all invertebrates were used as a proxy for trophic niche, and community
      wide metrics were obtained. Our empirically derived C/N ratios differed from
      those previously reported, diverging from model predictions of global C and N
      cycling, which was unexpected. An assessment of the relative response of the
      different functional groups to the change from agricultural grassland to woodland
      was performed. This showed that abundance of herbivores, microbivores, and
      micropredators were stimulated, while omnivores and macropredators were inhibited
      in the grassland. Differences between stable isotope ratios and community-wide
      metrics, highlighted habitats with similar taxa had different SFWs, using
      different basal resources, either driven by root or litter derived resources.
      Overall, we conclude that plant type can act as a top-down driver of community
      functioning and that differing land management can impact on the whole SFW. 

PMID- 24455157
TI  - Growing season net ecosystem CO2 exchange of two desert ecosystems with alkaline
      soils in Kazakhstan.
AB  - Central Asia is covered by vast desert ecosystems, and the majority of these
      ecosystems have alkaline soils. Their contribution to global net ecosystem CO2
      exchange (NEE) is of significance simply because of their immense spatial extent.
      Some of the latest research reported considerable abiotic CO2 absorption by
      alkaline soil, but the rate of CO2 absorption has been questioned by peer
      communities. To investigate the issue of carbon cycle in Central Asian desert
      ecosystems with alkaline soils, we have measured the NEE using eddy covariance
      (EC) method at two alkaline sites during growing season in Kazakhstan. The
      diurnal course of mean monthly NEE followed a clear sinusoidal pattern during
      growing season at both sites. Both sites showed significant net carbon uptake
      during daytime on sunny days with high photosynthetically active radiation (PAR)
      but net carbon loss at nighttime and on cloudy and rainy days. NEE has strong
      dependency on PAR and the response of NEE to precipitation resulted in an initial
      and significant carbon release to the atmosphere, similar to other ecosystems.
      These findings indicate that biotic processes dominated the carbon processes, and
      the contribution of abiotic carbon process to net ecosystem CO2 exchange may be
      trivial in alkaline soil desert ecosystems over Central Asia. 

PMID- 24455158
TI  - Shared patterns of species turnover between seaweeds and seed plants break down
      at increasing distances from the sea.
AB  - We tested for correlations in the degree of spatial similarity between algal and
      terrestrial plants communities along 5500 km of temperate Australian coastline
      and whether the strength of correlation weakens with increasing distance from the
      coast. We identified strong correlations between macroalgal and terrestrial plant
      communities within the first 100 km from shore, where the strength of these
      marine-terrestrial correlations indeed weakens with increasing distance inland.
      As such, our results suggest that marine-driven community homogenization
      processes decompose with increasing distance from the shore toward inland. We
      speculate that the proximity to the marine environment produces lower levels of
      community turnover on land, and this effect decreases progressively farther
      inland. Our analysis suggests underlying ecological and evolutionary processes
      that give rise to continental-scale biogeographic influence from sea to land. 

PMID- 24455159
TI  - The effects of fire on ant trophic assemblage and sex allocation.
AB  - Fire plays a key role in ecosystem dynamics worldwide, altering energy flows and
      species community structure and composition. However, the functional mechanisms
      underlying these effects are not well understood. Many ground-dwelling animal
      species can shelter themselves from exposure to heat and therefore rarely suffer
      direct mortality. However, fire-induced alterations to the environment may change
      a species' relative trophic level within a food web and its mode of foraging. We
      assessed how fire could affect ant resource utilization at different scales in a
      Mediterranean forest. First, we conducted isotopic analyses on entire ant species
      assemblages and their potential food resources, which included plants and other
      arthropods, in burned and unburned plots 1 year postfire. Second, we measured the
      production of males and females by nests of a fire-resilient species,
      Aphaenogaster gibbosa, and analyzed the differences in isotopic values among
      workers, males, and females to test whether fire constrained resource allocation.
      We found that, in spite of major modifications in biotic and abiotic conditions,
      fire had little impact on the relative trophic position of ant species. The
      studied assemblage was composed of species with a wide array of diets. They
      ranged from being mostly herbivorous to completely omnivorous, and a given
      species' trophic level was the same in burned and unburned plots. In A. gibbosa
      nests, sexuals had greater delta(15)N values than workers in both burned and
      unburned plots, which suggests that the former had a more protein-rich diet than
      the latter. Fire also appeared to have a major effect on A. gibbosa sex
      allocation: The proportion of nests that produced male brood was greater on
      burned zones, as was the mean number of males produced per nest with the same
      reproductive investment. Our results show that generalist ants with relatively
      broad diets maintained a constant trophic position, even following a major
      disturbance like fire. However, the dramatically reduced production of females on
      burned zones compared to unburned zones 1 year postfire may result in
      considerably reduced recruitment of new colonies in the mid to long term, which
      could yield genetic bottlenecks and founder effects. Our study paves the way for
      future functional analyses of fire-induced modifications in ant populations and
      communities. 

PMID- 24455160
TI  - Evidence of constant diversification punctuated by a mass extinction in the
      African cycads.
AB  - The recent evidence that extant cycads are not living fossils triggered a renewed
      search for a better understanding of their evolutionary history. In this study,
      we investigated the evolutionary diversification history of the genus
      Encephalartos, a monophyletic cycad endemic to Africa. We found an antisigmoidal
      pattern with a plateau and punctual explosive radiation. This pattern is typical
      of a constant radiation with mass extinction. The rate shift that we found may
      therefore be a result of a rapid recolonization of niches that have been emptied
      owing to mass extinction. Because the explosive radiation occurred during the
      transition Pliocene-Pleistocene, we argued that the processes might have been
      climatically mediated. 

PMID- 24455161
TI  - Acorns containing deeper plumule survive better: how white oaks counter embryo
      excision by rodents.
AB  - Several squirrel species excise the embryo of acorns of most white oak species to
      arrest germination for long-term storage. However, it is not clear how these
      acorns counter embryo excision and survive in the arms race of coevolution. In
      this study, we simulated the embryo excision behavior of squirrels by removing 4
      mm of cotyledon from the apical end of white oak acorns differing in embryo
      depths to investigate the effects of embryo excision on acorn germination and
      seedling performance of white oak species. The embryo depth in the cotyledons was
      significantly different among white oak acorns, with Quercus mongolica containing
      the embryo most deeply in the acorns. We found that artificial embryo excision
      significantly decreased acorn germination rates of Quercus variabilis, Quercus
      acutissima, Quercus aliena, Quercus aliena var. acutiserrata, Quercus serrata.
      var. brevipetiolata but not Q. mongolica. Artificial embryo excision exerted
      significant negative impacts on seedling performance of all oak species except
      Quercus aliena. Our study demonstrates the role of embryo depth of acorns in
      countering embryo excision by squirrels and may explain the fact that squirrels
      do not perform embryo excision in acorns of Q. mongolica with deeper embryos.
      This apparent adaptation of acorns sheds light on the coevolutionary dynamics
      between oaks and their seed predators. 

PMID- 24455162
TI  - No evidence for size-assortative mating in the wild despite mutual mate choice in
      sex-role-reversed pipefishes.
AB  - Size-assortative mating is a nonrandom association of body size between members
      of mating pairs and is expected to be common in species with mutual preferences
      for body size. In this study, we investigated whether there is direct evidence
      for size-assortative mating in two species of pipefishes, Syngnathus floridae and
      S. typhle, that share the characteristics of male pregnancy, sex-role reversal,
      and a polygynandrous mating system. We take advantage of microsatellite-based
      "genetic-capture" techniques to match wild-caught females with female genotypes
      reconstructed from broods of pregnant males and use these data to explore
      patterns of size-assortative mating in these species. We also develop a
      simulation model to explore how positive, negative, and antagonistic preferences
      of each sex for body size affect size-assortative mating. Contrary to
      expectations, we were unable to find any evidence of size-assortative mating in
      either species at different geographic locations or at different sampling times.
      Furthermore, two traits that potentially confer a fitness advantage in terms of
      reproductive success, female mating order and number of eggs transferred per
      female, do not affect pairing patterns in the wild. Results from model
      simulations demonstrate that strong mating preferences are unlikely to explain
      the observed patterns of mating in the studied populations. Our study shows that
      individual mating preferences, as ascertained by laboratory-based mating trials,
      can be decoupled from realized patterns of mating in the wild, and therefore,
      field studies are also necessary to determine actual patterns of mate choice in
      nature. We conclude that this disconnect between preferences and assortative
      mating is likely due to ecological constraints and multiple mating that may limit
      mate choice in natural populations. 

PMID- 24455163
TI  - Quantifying habitat impacts of natural gas infrastructure to facilitate
      biodiversity offsetting.
AB  - Habitat degradation through anthropogenic development is a key driver of
      biodiversity loss. One way to compensate losses is "biodiversity offsetting"
      (wherein biodiversity impacted is "replaced" through restoration elsewhere). A
      challenge in implementing offsets, which has received scant attention in the
      literature, is the accurate determination of residual biodiversity losses. We
      explore this challenge for offsetting gas extraction in the Ustyurt Plateau,
      Uzbekistan. Our goal was to determine the landscape extent of habitat impacts,
      particularly how the footprint of "linear" infrastructure (i.e. roads,
      pipelines), often disregarded in compensation calculations, compares with "hub"
      infrastructure (i.e. extraction facilities). We measured vegetation cover and
      plant species richness using the line-intercept method, along transects running
      from infrastructure/control sites outward for 500 m, accounting for wind
      direction to identify dust deposition impacts. Findings from 24 transects were
      extrapolated to the broader plateau by mapping total landscape infrastructure
      network using GPS data and satellite imagery. Vegetation cover and species
      richness were significantly lower at development sites than controls. These
      differences disappeared within 25 m of the edge of the area physically occupied
      by infrastructure. The current habitat footprint of gas infrastructure is 220 +/-
      19 km(2) across the Ustyurt (total ~ 100,000 km(2)), 37 +/- 6% of which is linear
      infrastructure. Vegetation impacts diminish rapidly with increasing distance from
      infrastructure, and localized dust deposition does not conspicuously extend the
      disturbance footprint. Habitat losses from gas extraction infrastructure cover
      0.2% of the study area, but this reflects directly eliminated vegetation only.
      Impacts upon fauna pose a more difficult determination, as these require
      accounting for behavioral and demographic responses to disturbance by elusive
      mammals, including threatened species. This study demonstrates that impacts of
      linear infrastructure in regions such as the Ustyurt should be accounted for not
      just with respect to development sites but also associated transportation and
      delivery routes. 

PMID- 24455164
TI  - A meta-analysis of declines in local species richness from human disturbances.
AB  - There is high uncertainty surrounding the magnitude of current and future
      biodiversity loss that is occurring due to human disturbances. Here, we present a
      global meta-analysis of experimental and observational studies that report 327
      measures of change in species richness between disturbed and undisturbed habitats
      across both terrestrial and aquatic biomes. On average, human-mediated
      disturbances lead to an 18.3% decline in species richness. Declines in species
      richness were highest for endotherms (33.2%), followed by producers (25.1%), and
      ectotherms (10.5%). Land-use change and species invasions had the largest impact
      on species richness resulting in a 24.8% and 23.7% decline, respectively,
      followed by habitat loss (14%), nutrient addition (8.2%), and increases in
      temperature (3.6%). Across all disturbances, declines in species richness were
      greater for terrestrial biomes (22.4%) than aquatic biomes (5.9%). In the
      tropics, habitat loss and land-use change had the largest impact on species
      richness, whereas in the boreal forest and Northern temperate forests, species
      invasions had the largest impact on species richness. Along with revealing trends
      in changes in species richness for different disturbances, biomes, and taxa, our
      results also identify critical knowledge gaps for predicting the effects of human
      disturbance on Earth's biomes. 

PMID- 24455165
TI  - The importance of rare species: a trait-based assessment of rare species
      contributions to functional diversity and possible ecosystem function in tall
      grass prairies.
AB  - The majority of species in ecosystems are rare, but the ecosystem consequences of
      losing rare species are poorly known. To understand how rare species may
      influence ecosystem functioning, this study quantifies the contribution of
      species based on their relative level of rarity to community functional diversity
      using a trait-based approach. Given that rarity can be defined in several
      different ways, we use four different definitions of rarity: abundance (mean and
      maximum), geographic range, and habitat specificity. We find that rarer species
      contribute to functional diversity when rarity is defined by maximum abundance,
      geographic range, and habitat specificity. However, rarer species are
      functionally redundant when rarity is defined by mean abundance. Furthermore,
      when using abundance-weighted analyses, we find that rare species typically
      contribute significantly less to functional diversity than common species due to
      their low abundances. These results suggest that rare species have the potential
      to play an important role in ecosystem functioning, either by offering novel
      contributions to functional diversity or via functional redundancy depending on
      how rare species are defined. Yet, these contributions are likely to be greatest
      if the abundance of rare species increases due to environmental change. We argue
      that given the paucity of data on rare species, understanding the contribution of
      rare species to community functional diversity is an important first step to
      understanding the potential role of rare species in ecosystem functioning. 

PMID- 24455167
TI  - Locally-generated Acetaldehyde Contributes to the Effects of Ethanol on
      Neurosteroids and LTP in the Hippocampus.
AB  - BACKGROUND: As severe alcohol intoxication impairs memory function, a high
      concentration of ethanol (60 mM) acutely inhibits long-term potentiation (LTP), a
      cellular model of learning and memory, in rat hippocampal slices. Neurosteroids
      are involved in this LTP inhibition. We recently reported that the inhibitory
      effects of 60 mM ethanol are blocked by 4-methylpyrazole (4MP), an inhibitor of
      alcohol dehydrogenase, suggesting that acetaldehyde locally generated within the
      hippocampus participates in LTP inhibition. AIM: We investigated whether
      acetaldehyde generated by ethanol metabolism contributes to neurosteroidogenesis
      and LTP inhibition. RESULTS: Like 60 mM ethanol, we found that exogenous
      acetaldehyde enhanced neurosteroid immunostaining in CA1 pyramidal neurons, and
      that augmented neurosteroid immunostaining by high ethanol alone was blocked by
      4MP but not by inhibitors of other ethanol metabolism pathways. The inhibitory
      effects of 60 mM ethanol on LTP were mimicked by a lower concentration of ethanol
      (20 mM) plus acetaldehyde (60 MUM), although neither agent alone was effective at
      these concentrations, suggesting that 60 mM ethanol inhibits LTP via multiple
      actions, one of which involves acetaldehyde and the other of which requires only
      20 mM ethanol. The effects of ethanol and acetaldehyde on neurosteroid staining
      and LTP were overcome by inhibition of neurosteroid synthesis and by blockade of
      N-methyl-D-aspartate receptors (NMDARs). CONCLUSION: These observations indicate
      that acetaldehyde generated by local ethanol metabolism within the hippocampus
      serves as a signal for neurosteroid synthesis in pyramidal neurons, and
      participates in the synaptic dysfunction associated with severe alcohol
      intoxication.

PMID- 24455168
TI  - New directions and technologies for minimal invasive thoracic surgery.

PMID- 24455170
TI  - Anesthetic consideration for nonintubated VATS.
AB  - In the recent decade, nonintubated-intubated video-assisted thoracoscopic surgery
      (VATS) has been extensively performed and evaluated. The indicated surgical
      procedures and suitable patient groups are steadily increasing. Perioperative
      anesthetic management presents itself as a fresh issue for the iatrogenic open
      pneumothorax, which is intended for unilateral lung collapse to create a steady
      surgical field, and the ensuing physiologic derangement involving ventilatory and
      hemodynamic perspectives. With appropriate monitoring, meticulous employment of
      regional anesthesia, sedation, vagal block, and ventilatory support, nonintubated
      VATS is proved to be a safe alternative to the conventional intubated general
      anesthesia. 

PMID- 24455169
TI  - Nonintubated thoracoscopic surgery: state of the art and future directions.
AB  - Video-assisted thoracoscopic surgery (VATS) has become a common and globally
      accepted surgical approach for a variety of thoracic diseases. Conventionally, it
      is performed under tracheal intubation with double lumen tube or bronchial
      blocker to achieve single lung ventilation. Recently, VATS without tracheal
      intubation were reported to be feasible and safe in a series of VATS procedures,
      including management of pneumothorax, wedge resection of pulmonary tumors,
      excision of mediastinal tumors, lung volume reduction surgery, segmentectomy, and
      lobectomy. Patients undergoing nonintubated VATS are anesthetized using regional
      anesthesia in a spontaneously single lung breathing status after iatrogenic open
      pneumothorax. Conscious sedation is usually necessary for longer and intensively
      manipulating procedures and intraoperative cough reflex can be effectively
      inhibited with intrathoracic vagal blockade on the surgical side. The early
      outcomes of nonintubated VATS include a faster postoperative recovery and less
      complication rate comparing with its counterpart of intubated general anesthesia,
      by which may translate into a fast track VATS program. The future directions of
      nonintubated VATS should focus on its long-term outcomes, especially on
      oncological perspectives of survival in lung cancer patients. For now, it is
      still early to conclude the benefits of this technique, however, an educating and
      training program may be needed to enable both thoracic surgeons and
      anesthesiologists providing an alternative surgical option in their caring
      patients. 

PMID- 24455171
TI  - Single-port video-assisted thoracoscopic surgery for lung cancer.
AB  - In 2004, novel results using pulmonary wedge resection executed through single
      port video-assisted thoracoscopic surgery (VATS) was first described. Since that
      time, single-port VATS has been advocated for the treatment of a spectrum of
      thoracic diseases, especially lung cancer. Lung cancer remains one of the top
      three cancer-related deaths in Taiwan, and surgical resection remains the "gold
      standard" for early-stage lung cancer. Anatomical resections (including
      pneumonectomy, lobectomy, and segmentectomy) remain the primary types of lung
      cancer surgery, regardless of whether conventional open thoracotomy, or 4/3/2
      ports VATS are used. In the past three years, several pioneers have reported
      their early experiences with single-port VATS lobectomy, segmentectomy, and
      pneumonectomy for lung cancer. Our goal was to appraise their findings and review
      the role of single-port VATS in the treatment of lung cancer. In addition, the
      current concept of mini-invasive surgery involves not only smaller resections
      (requiring only a few incisions), but also sub-lobar resection as segmentectomy.
      Therefore, our review will also address these issues. 

PMID- 24455172
TI  - Videoscope-assisted cardiac surgery.
AB  - Videoscope-assisted cardiac surgery (VACS) offers a minimally invasive platform
      for most cardiac operations such as coronary and valve procedures. It includes
      robotic and thoracoscopic approaches and each has strengths and weaknesses. The
      success depends on appropriate hardware setup, staff training, and
      troubleshooting efficiency. In our institution, we often use VACS for robotic
      left-internal-mammary-artery takedown, mitral valve repair, and various intra
      cardiac operations such as tricuspid valve repair, combined Maze procedure,
      atrial septal defect repair, ventricular septal defect repair, etc. Hands-on
      reminders and updated references are provided for reader's further understanding
      of the topic. 

PMID- 24455173
TI  - Nonintubated thoracoscopic surgery using regional anesthesia and vagal block and
      targeted sedation.
AB  - OBJECTIVE: Thoracoscopic surgery without endotracheal intubation is a novel
      technique for diagnosis and treatment of thoracic diseases. This study reported
      the experience of nonintubated thoracoscopic surgery in a tertiary medical center
      in Taiwan. METHODS: From August 2009 through August 2013, 446 consecutive
      patients with lung or pleural diseases were treated by nonintubated thoracoscopic
      surgery. Regional anesthesia was achieved by thoracic epidural anesthesia or
      internal intercostal blockade. Targeted sedation was performed with propofol
      infusion to achieve a bispectral index value between 40 and 60. The demographic
      data and clinical outcomes were evaluated by retrospective chart review. RESULTS:
      Thoracic epidural anesthesia was used in 290 patients (65.0%) while internal
      intercostal blockade was used in 156 patients (35.0%). The final diagnosis were
      primary lung cancer in 263 patients (59.0%), metastatic lung cancer in 38 (8.5%),
      benign lung tumor in 140 (31.4%), and pneumothorax in 5 (1.1%). The median
      anesthetic induction time was 30 minutes by thoracic epidural anesthesia and was
      10 minutes by internal intercostal blockade. The operative procedures included
      lobectomy in 189 patients (42.4%), wedge resection in 229 (51.3%), and
      segmentectomy in 28 (6.3%). Sixteen patients (3.6%) required conversion to
      tracheal intubation because of significant mediastinal movement (seven patients),
      persistent hypoxemia (two patients), dense pleural adhesions (two patients),
      ineffective epidural anesthesia (two patients), bleeding (two patients), and
      tachypnea (one patient). One patient (0.4%) was converted to thoracotomy because
      of bleeding. No mortality was noted in our patients. CONCLUSIONS: Nonintubated
      thoracoscopic surgery is technically feasible and safe and can be a less invasive
      alternative for diagnosis and treatment of thoracic diseases.

PMID- 24455174
TI  - Analysis of feasibility and safety of complete video-assisted thoracoscopic
      resection of anatomic pulmonary segments under non-intubated anesthesia.
AB  - OBJECTIVE: To explore the feasibility and safety of complete video-assisted
      thoracoscopic surgery (C-VATS) under non-intubated anesthesia for the resection
      of anatomic pulmonary segments in the treatment of early lung cancer (T1N0M0),
      benign lung diseases and lung metastases. METHODS: The clinical data of patients
      undergoing resection of anatomic pulmonary segments using C-VATS under non
      intubated anesthesia in the First Affiliated Hospital of Guangzhou Medical
      University from July 2011 to November 2013 were retrospectively analyzed to
      evaluate the feasibility and safety of this technique. RESULTS: The procedures
      were successfully completed in 15 patients, including four men and eleven women.
      The average age was 47 [21-74] years. There were ten patients with
      adenocarcinoma, one with pulmonary metastases, and four with benign lung lesions.
      The resected sites included: right upper apical segment, two; right lower dorsal
      segment, one; right lower basal segment, two; left upper lingular segment, three;
      left upper apical segment, one; left upper anterior apical segment, two; left
      upper posterior segment, one; left lower basal segment, one; left upper posterior
      and apical segments, one; and left upper anterior and apical segments plus wedge
      resection of the posterior segment, one. One case had intraoperative bleeding,
      which was controlled with thoracoscopic operation and no blood transfusion was
      required. No thoracotomy or perioperative death was noted. Two patients had
      postoperative bleeding without the need for blood transfusions, and were cured
      and discharged. The pathologic stage for all patients with primary lung cancer
      was IA. After 4-19 months of follow-up, no tumor recurrence and metastasis was
      found. The overall mean operative length was 166 minutes (range 65-285 minutes),
      mean blood loss 75 mL (range 5-1,450 mL), mean postoperative chest drainage 294
      mL (range 0-1,165 mL), mean chest drainage time 2 days (range 0-5 days), and mean
      postoperative hospital stay 5 days (range 3-8 days). CONCLUSIONS: Complete video
      assisted throacoscopic segmentectomy under anesthesia without endotracheal
      intubation is a safe and feasible technique that can be used to treat a selected
      group of IA patients with primary lung cancer, lung metastases and benign
      diseases.

PMID- 24455175
TI  - Comparative study of systematic thoracoscopic lymphadenectomy and conventional
      thoracotomy in resectable non-small cell lung cancer.
AB  - OBJECTIVE: To assess the feasibility and safety of the video-assisted
      thoracoscopy surgery (VATS) systematic lymph node dissection in resectable non
      small cell lung cancer (NSCLC). METHODS: The clinical data of patients with NSCLC
      who underwent VATS or thoracotomy combined with lobectomy and systematic
      lymphadenectomy from January 2001 to January 2008 were retrospectively analyzed
      to identify their demographic parameters, number of dissected lymph nodes and
      postoperative complications. RESULTS: A total of 5,620 patients were enrolled in
      this study, with 2,703 in the VATS group, including 1,742 men (64.4%), and 961
      women (35.6%), aged 59.5+/-10.9 years; and 2,917 in the thoracotomy group,
      including 2,163 men (74.2%), and 754 women (25.8%), aged 58.5+/-10.4 years.
      Comparing the VATS with the thoracotomy groups, the mean operative time was 146
      vs. 157 min, with a significant difference (P<0.001); and the average blood loss
      was 162 vs. 267 mL, with a significant difference (P<0.001). Comparing the two
      groups of patients data, the number of lymph node dissection: 18.03 in the VATS
      group and 15.07 in the thoracotomy group on average, with a significant
      difference (P<0.001); postoperative drainage time: 4.5 days in the VATS group and
      6.37 days in the thoracotomy group on average, with a significant difference
      (P<0.001); postoperative hospital stay: 6.5 days in the VATS group and 8.37 days
      in the thoracotomy group on average, with a significant difference (P<0.001);
      proportion of postoperative chylothorax: 0.2% (4/2,579) in the VATS group and
      0.4% (10/2,799) in the thoracotomy group, without significant difference
      (P>0.05). CONCLUSIONS: For patients with resectable NSCLC, VATS systematic lymph
      node dissection is safe and effective with fewer postoperative complications, and
      significantly faster postoperative recovery compared with traditional open chest
      surgery.

PMID- 24455176
TI  - Video-assisted thoracoscopic surgery for postoperative recurrent primary
      spontaneous pneumothorax.
AB  - OBJECTIVES: Postoperative recurrent primary spontaneous pneumothorax (PSP) is a
      troublesome complication and an important issue to be discussed. This study is to
      determine whether Re-video assisted thoracoscopic surgery (VATS) should be
      performed for postoperative recurrent PSP (PORP). MATERIALS AND METHODS: Patients
      who had underwent needlescopic VATS for PSP between Jan. 2007 and Dec. 2011 were
      reviewed. RESULTS: VATS was initially performed on 239 patients with PSP in
      total. Eleven patients were found to have PORP during a follow-up period of 36.95
      months. Nine patients received Re-VATS and only two patients receiving
      conservative treatment had no further recurrence. No conversion to thoracotomy,
      blood transfusion and prolong air leak were recorded. CONCLUSIONS: Even for
      smaller size cases, Re-VATS, which is technically feasible, safe and effective
      with better cosmetics and minor postoperative pain, should be a strong contender
      as priority treatment.

PMID- 24455177
TI  - Robotic mitral valve repair in infective endocarditis.
AB  - BACKGROUND: Robotic mitral surgery is the most common robotic cardiac procedures.
      However, in mitral endocarditis the repair become more challenging especially in
      minimally approach. We applied robotic surgery in mitral endocarditis repair and
      reviewed our surgical methods and results. PATIENTS: From January 2012 to
      December 2013, 12 patients with mitral endocarditis in National Taiwan University
      Hospital were operated via robotic assisted repair. Age of them was among 21 to
      65 years old, mean 43. RESULTS: The vegetation involves anterior leaflet in 3,
      posterior leaflet in 8 and commissural leaflet in 4. Mean cardiopulmonary bypass
      time is 124 minutes and cross clamp time is 89 minutes. There was no stroke and
      no operation death. Mitral valve repair technique including anterior leaflet
      patch augmentation in 2, direct closure of rupture hole on anterior leaflet in
      one, plication commissural leaflet in 2, and artificial chordae in 10. There was
      no mitral regurgitation detected immediately after weaning of cardiopulmonary
      bypass. All of them got free-from-regurgitation or -stenosis rate was 100% at one
      year follow. CONCLUSIONS: Although mitral infective endocarditis is complex and
      difficult to repair, robotic mitral repair in infective endocarditis is feasible.
      Even in the complex repair group, the cardiopulmonary bypass time is not
      prolonged and the result is good.

PMID- 24455178
TI  - Natural orifice surgery in thoracic surgery.

PMID- 24455179
TI  - "Epigenetic memory" phenomenon in induced pluripotent stem cells.
AB  - To date biomedicine and pharmacology have required generating new and more
      consummate models. One of the most perspective trends in this field is using
      induced pluripotent stem cells (iPSCs). iPSC application requires careful high
      throughput analysis at the molecular, epigenetic, and functional levels. The
      methods used have revealed that the expression pattern of genes and microRNA, DNA
      methylation, as well as the set and pattern of covalent histone modifications in
      iPSCs, are very similar to those in embryonic stem cells. Nevertheless, iPSCs
      have been shown to possess some specific features that can be acquired during the
      reprogramming process or are remnants of epigenomes and transcriptomes of the
      donor tissue. These residual signatures of epigenomes and transcriptomes of the
      somatic tissue of origin were termed "epigenetic memory." In this review, we
      discuss the "epigenetic memory" phenomenon in the context of the reprogramming
      process, its influence on iPSC properties, and the possibilities of its
      application in cell technologies. 

PMID- 24455180
TI  - The role of integrins in the development and homeostasis of the epidermis and
      skin appendages.
AB  - Integrins play a critical role in the regulation of adhesion, migration,
      proliferation, and differentiation of cells. Because of the variety of the
      functions they play in the cell, they are necessary for the formation and
      maintenance of tissue structure integrity. The trove of data accumulated by
      researchers suggests that integrins participate in the morphogenesis of the
      epidermis and its appendages. The development of mice with tissue-specific
      integrin genes knockout and determination of the genetic basis for a number of
      skin diseases in humans showed the significance of integrins in the biology,
      physiology, and morphogenesis of the epidermis and hair follicles. This review
      discusses the data on the role of different classes of integrin receptors in the
      biology of epidermal cells, as well as the development of the epidermis and hair
      follicles. 

PMID- 24455182
TI  - Antiviral Activity of Binase against the Pandemic Influenza A (H1N1) Virus.
AB  - The lack of effective antiviral drugs restricts the control of the dangerous RNA
      containing influenza A (H1N1) virus. Extracellular ribonuclease of Bacilli
      (binase) was shown to manifest antiviral activity during single- and multi-cycle
      viral replication in the range of concentrations non-toxic to epithelial cells
      and 0.01-0.1 multiplicity of infection. During antiviral treatment for 15-30 min,
      the concentration of 1 MUg/ml binase reduced the amount of focus-forming units of
      viruses by a factor of 3-10 and suppressed the virus-induced cytopathic effect in
      A549 human lung cells. The possible mechanisms of interaction between the virus
      and enzyme are discussed. Positive charges in both binase and viral hemagglutinin
      cause electrostatic interaction with negatively charged sialic acid on the host
      cell's surface followed by its penetration into the cell. Capsid elimination and
      release of viral RNA from endosome to the cytoplasm allows catalytic RNA cleavage
      by internalized binase. The data obtained confirm that binase is an effective
      antiviral agent against the pandemic influenza A (H1N1) virus. Certain progress
      in this field is associated with clarifying the detailed mechanism underlying the
      antiviral action of binase and development of the most effective way for its
      practical use. 

PMID- 24455181
TI  - Aptamers: problems, solutions and prospects.
AB  - Aptamers are short single-stranded oligonucleotides that are capable of binding
      various molecules with high affinity and specificity. When the technology of
      aptamer selection was developed almost a quarter of a century ago, a suggestion
      was immediately put forward that it might be a revolutionary start into solving
      many problems associated with diagnostics and the therapy of diseases. However,
      multiple attempts to use aptamers in practice, although sometimes successful,
      have been generally much less efficient than had been expected initially. This
      review is mostly devoted not to the successful use of aptamers but to the
      problems impeding the widespread application of aptamers in diagnostics and
      therapy, as well as to approaches that could considerably expand the range of
      aptamer application. 

PMID- 24455183
TI  - Competition within Introns: Splicing Wins over Polyadenylation via a General
      Mechanism.
AB  - Most eukaryotic messenger RNAs are capped, spliced, and polyadenylated via co
      transcriptional processes that are coupled to each other and to the transcription
      machinery. Coordination of these processes ensures correct RNA maturation and
      provides for the diversity of the transcribed isoforms. Thus, RNA processing is a
      chain of events in which the completion of one event is coupled to the initiation
      of the next one. In this context, the relationship between splicing and
      polyadenylation is an important aspect of gene regulation. We have found that
      cryptic polyadenylation signals are widely distributed over the intron sequences
      of Drosophila melanogaster. As shown by analyzing the distribution of genes
      arranged in a nested pattern, where one gene is fully located within an intron of
      another gene, overlapping of putative polyadenylation signals is a fairly common
      event affecting about 17% of all genes. Here we show that polyadenylation signals
      are silenced within introns: the poly(A) signal is utilized in the exonic but not
      in the intronic regions of the transcript. The transcription does not end within
      the introns, either in a transient reporter system or in the genomic context,
      while deletion of the 5'-splice site restores their functionality. According to a
      full Drosophila transcriptome analysis, utilization of intronic polyadenylation
      signals occurs very rarely and such events are likely to be inducible. These
      results confirm that the transcription apparatus ignores premature
      polyadenylation signals for as long as they are intronic. 

PMID- 24455184
TI  - 3D Structure Modeling of Alpha-Amino Acid Ester Hydrolase from Xanthomonas
      rubrilineans.
AB  - Alpha-amino acid ester hydrolase (EC 3.1.1.43, AEH) is a promising biocatalyst
      for the production of semi-synthetic beta-lactam antibiotics, penicillins and
      cephalosporins. The AEH gene from Xanthomonas rubrilineans (XrAEH) was recently
      cloned in this laboratory. The three-dimensional structure of XrAEH was simulated
      using the homology modeling method for rational design experiments. The analysis
      of the active site was performed, and its structure was specified. The key amino
      acid residues in the active site - the catalytic triad (Ser175, His341 and
      Asp308), oxyanion hole (Tyr83 and Tyr176), and carboxylate cluster (carboxylate
      groups of Asp209, Glu310 and Asp311) - were identified. It was shown that the
      optimal configuration of residues in the active site occurs with a negative net
      charge -1 in the carboxylate cluster. Docking of different substrates in the AEH
      active site was carried out, which allowed us to obtain structures of XrAEH
      complexes with the ampicillin, amoxicillin, cephalexin, D-phenylglycine, and 4
      hydroxy-D-phenylglycine methyl ester. Modeling of XrAEH enzyme complexes with
      various substrates was used to show the structures for whose synthesis this
      enzyme will show the highest efficiency. 

PMID- 24455185
TI  - Neolactoferrin as a stimulator of innate and adaptive immunity.
AB  - The effect of the innovative product Neolactoferrin, a natural combination of
      recombinant human lactoferrin (90%) and goat lactoferrin (10%) isolated from the
      milk of transgenic goats carrying the full-length human lactoferrin gene, on
      human immune system cells was studied. Neolactoferrin enhanced the production of
      IL-1beta. Neolactoferrin saturated with iron ions increased the synthesis of pro
      inflammatory cytokine TNFalpha. It determined the direction of the
      differentiation of precursor dendrite cells. Under the action of T cells,
      Neolactoferrin amplified the expression of the transcription factors responsible
      for the differentiation of Th- and Treg-cells and stimulated the production of
      both IFNgamma and IL-4. The results suggest that Neolactoferrin exhibits an
      immunotropic activity and hinders the development of immune inflammatory
      processes. Iron saturation of Neolactoferrin increases its pro-inflammatory
      activity. 

PMID- 24455186
TI  - Depolarization-induced calcium-independent synaptic vesicle exo- and endocytosis
      at frog motor nerve terminals.
AB  - The transmitter release and synaptic vesicle exo- and endocytosis induced by
      constant current depolarization of nerve terminals were studied by microelectode
      extracellular recording of miniature endplate currents and fluorescent microscopy
      (FM 1-43 styryl dye). Depolarization of the plasma membrane of nerve terminals in
      the control specimen was shown to significantly increase the MEPC frequency
      (quantal transmitter release) and exocytotic rate (FM 1-43 unloading from the
      synaptic vesicles preliminarily stained with the dye), which was caused by a rise
      in the intracellular Ca(2+) concentration due to opening of voltage-gated Ca
      channels. A slight increase in the MEPC frequency and in the rate of synaptic
      vesicle exocytosis was observed under depolarization in case of blockade of Ca
      channels and chelating of intracellular Ca(2+) ions (cooperative action of Cd(2+)
      and EGTA-AM). The processes of synaptic vesicle endocytosis (FM 1-43 loading)
      were proportional to the number of synaptic vesicles that had undergone
      exocytosis both in the control and in case of cooperative action of Cd(2+) and
      EGTA-AM. A hypothesis has been put forward that Ca-independent synaptic vesicle
      exo- and endocytosis that can be induced directly by depolarization of the
      membrane exists in the frog motor terminal in addition to the conventional Ca
      dependent process. 

PMID- 24455187
TI  - Alu- and 7SL RNA Analogues Suppress MCF-7 Cell Viability through Modulating the
      Transcription of Endoplasmic Reticulum Stress Response Genes.
AB  - 11% of the human genome is composed of Alu-retrotransposons, whose transcription
      by RNA polymerase III (Pol III) leads to the accumulation of several hundreds to
      thousands of Alu-RNA copies in the cytoplasm. Expression of Alu-RNA Pol III is
      significantly increased at various levels of stress, and the increase in the Alu
      RNA level is accompanied by a suppression of proliferation, a decrease in
      viability, and induction of apoptotic processes in human cells. However, the
      question about the biological functions of Pol III Alu-transcripts, as well as
      their mechanism of action, remains open. In this work, analogues of Alu-RNA and
      its evolutionary ancestor, 7SL RNA, were synthesized. Transfection of human
      breast adenocarcinoma MCF-7 cells with the Alu-RNA and 7SL RNA analogues is
      accompanied by a decrease in viability and by induction of proapoptotic changes
      in these cells. The analysis of the combined action of these analogues and
      actinomycin D or tamoxifen revealed that the decreased viability of MCF-7 cells
      transfected with Alu-RNA and 7SL RNA was due to the modulation of transcription.
      A whole transcriptome analysis of gene expression revealed that increased gene
      expression of the transcription regulator NUPR1 (p8), as well as the
      transcription factor DDIT3 (CHOP), occurs under the action of both the Alu- and
      7SL RNA analogues on MCF-7 cells. It has been concluded that induction of
      proapoptotic changes in human cells under the influence of the Alu-RNA and 7SL
      RNA analogues is related to the transcriptional activation of the genes of
      cellular stress factors, including the endoplasmic reticulum stress response
      factors. 

PMID- 24455188
TI  - Polyreactive monoclonal autoantibodies in multiple sclerosis: functional
      selection from phage display library and characterization by deep sequencing
      analysis.
AB  - Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system that primarily affects young and middle-aged people. It is
      widely accepted that B lymphocyte activation is required for MS progression.
      Despite the fact that the exact triggering mechanisms of MS remain enigmatic, one
      may suggest that MS can be induced by viral or bacterial infection in combination
      with specific genetic and environmental factors. Using deep sequencing and
      functional selection methodologies we characterized clones of poly- and cross
      reactive antibodies that are capable of simultaneous recognition of viral
      proteins and autoantigens. The latter, in turn, possibly may trigger MS
      progression through molecular mimicry. It was identified that two cross-reactive
      antigens are probably recognized by light or heavy chains individually. According
      to the high structural homology between selected autoantibodies and a number of
      various antiviral IgGs, we suggest that a wide range of pathogens, instead of a
      single virus, be regarded as possible triggers of MS. 

PMID- 24455189
TI  - Antidepressant Effect of Dimeric Dipeptide GSB-106, an Original Low-Molecular
      Weight Mimetic of BDNF.
AB  - A large amount of clinical and experimental data suggest the involvement of
      neurotrophins, in particular the brain-derived neurotrophic factor (BDNF), in
      depression pathogenesis. However, the therapeutic use of BDNF is limited because
      of its instability in biological fluids, poor blood-brain barrier (BBB)
      permeability, and the presence of side effects. A low-molecular-weight mimetic
      GSB-106, which is a substituted dimeric dipeptide bis(N-monosuccinyl-L-seryl-L
      lysine)hexamethylenediamide, was designed and synthesized based on the BDNF
      fourth loop structure at the V.V. Zakusov Institute of Pharmacology (RAMS). GSB
      106 was found to exhibit an antidepressant activity in various models of
      depressive-like state when administered intraperitoneally to outbred mice and
      rats. An effect for the substance, when administered daily for 4-5 days, was
      detected in the Porsolt forced swimming test (0.1 and 1.0 mg/kg) and in the tail
      suspension test in mice (1.0 and 1.5 mg/ kg). An effect for GSB-106 at doses of
      0.1 and 0.5 mg/kg was observed after a single application in experiments on rats
      in the Nomura water wheel test. The obtained evidence supports the hypothesis on
      the involvement of BDNF in the pathogenesis of various depression conditions,
      thus opening prospects for searching for new original antidepressants. 

PMID- 24455190
TI  - Three-dimensional model of mouse epidermis for experimental studies of psoriasis.
AB  - Three-dimensional models of skin and epidermis imitate the structure of real
      tissues and provide accurate information about certain skin conditions, such as
      psoriasis. A three-dimensional model of mouse epidermis was generated from the
      epidermal keratinocytes of newborn mice and treated with cytokines. The aim of
      this study was to evaluate this model as an experimental model of psoriasis and
      to assess the changes occurring in its structure and gene expression after the
      exposure to proinflammatory cytokines. Treatment of the three-dimensional model
      with either interleukin 17 or a combination of tumor necrosis factor and
      interferon gamma was shown to produce morphological changes, which were similar
      to acanthosis in psoriatic skin. The observed changes in gene expression of
      metalloproteinases and certain psoriasis biomarkers, such as mki67, krt16 and
      fosl1, were similar to the changes in patients' skin. Notably, changes caused by
      interleukin 17 were less evident than those caused by the combination of
      interferon gamma and tumor necrosis factor. On the contrary, HaCaT cells
      exhibited no significant changes in the expression of fosl1 and had decreased
      levels of mki67 after being treated with a combination of TNF and IFNG. Moreover,
      treatment with IL17 had no significant effect on krt16 and mki67 expression and
      even reduced the fosl1 levels. The findings suggest that artificially generated
      three-dimensional models of murine skin can be used to study psoriasis. 

PMID- 24455191
TI  - Intensity of Free Radical Processes in Rat Liver under Type 2 Diabetes and
      Introduction of Epifamin.
AB  - The effect of epifamin on free radical processes, the activity of caspase-1 and 
      3, aconitate hydratase and citrate content in rat's liver at experimentally
      induced type 2 diabetes mellitus (T2DM) was studied. The action of epifamin at
      T2DM leads to a decrease in biochemiluminescence parameters, characterizing the
      intensity of free radical processes, and changes in aconitase activity and
      citrate level towards the control. Activities of caspase-1 and caspase-3 in the
      tissue decreased by a factor of 2.4 and 1.6 in comparison with the levels at the
      disease. Apparently, epifamin-mediated correction of the level of melatonin,
      providing a significant antioxidant effect, promotes positive action on the free
      radical homeostasis. 

PMID- 24455192
TI  - Systemic heparinisation in laparoscopic live donor nephrectomy.
AB  - Introduction. Systemic heparinisation is advocated during laparoscopic live donor
      nephrectomy (LDN) as a preventative measure against renal vascular thrombosis
      during the warm ischaemic interval. This study compares the outcome with and
      without the administration of systemic heparinisation. Methods. A retrospective
      analysis was performed on 186 consecutive LDN patients between April 2008 and
      November 2012. Systemic heparin (2000-3000 IU) was administered intravenously to
      donors (hep n = 109). From January 2010, heparin was not used systemically in
      this group of LDN (no hep n = 77). Outcome measures included donor and recipient
      complications, initial graft function, and 12 month graft survival. Results. The
      demographics of both heparinised and non-heparinised donors were similar. The
      warm ischaemic time (WIT) was comparable in both groups (WIT; hep 5 +/- 3 versus
      no hep 5 +/- 3 minutes; P = 1.000). There was no difference in complication
      rates, no episodes of graft thrombosis, and no incidences of primary nonfunction
      in either group. Delayed graft function occurred in 4/109 and 1/77 (3.6% versus
      1.2%; P = 0.405) and there was no significant difference in graft survival (P =
      0.650). Conclusion. Omitting systemic heparinisation during laparoscopic donor
      nephrectomy is a feasible and safe approach that does not compromise donor or
      recipient outcome. 

PMID- 24455193
TI  - Liver Transplantation without Perioperative Transfusions Single-Center Experience
      Showing Better Early Outcome and Shorter Hospital Stay.
AB  - Background. Significant amounts of red blood cells (RBCs) transfusions are
      associated with poor outcome after liver transplantation (LT). We report our
      series of LT without perioperative RBC (P-RBC) transfusions to evaluate its
      influence on early and long-term outcomes following LT. Methods. A consecutive
      series of LT between 2006 and 2011 was analyzed. P-RBC transfusion was defined as
      one or more RBC units administrated during or <=48 hours after LT. We divided the
      cohort in "No-Transfusion" and "Yes-Transfusion." Preoperative status, graft
      quality, and intra- and postoperative variables were compared to assess P-RBC
      transfusion risk factors and postoperative outcome. Results. LT was performed in
      127 patients ("No-Transfusion" = 39 versus "Yes-Transfusion" = 88). While median
      MELD was significantly higher in Yes-Transfusion (11 versus 21; P = 0.0001)
      group, platelet count, prothrombin time, and hemoglobin were significantly lower.
      On multivariate analysis, the unique independent risk factor associated with P
      RBC transfusions was preoperative hemoglobin (P < 0.001). Incidence of
      postoperative bacterial infections (10 versus 27%; P = 0.03), median ICU (2
      versus 3 days; P = 0.03), and hospital stay (7.5 versus 9 days; P = 0.01) were
      negatively influenced by P-RBC transfusions. However, 30-day mortality (10 versus
      15%) and one- (86 versus 70%) and 3-year (77 versus 66%) survival were equivalent
      in both groups. Conclusions. Recipient MELD score was not a predictive factor for
      P-RBC transfusion. Patients requiring P-RBC transfusions had worse postoperative
      outcome. Therefore, maximum efforts must be focused on improving hemoglobin
      levels during waiting list time to prevent using P-RBC in LT recipients. 

PMID- 24455194
TI  - Long-term outcomes of rheohaemapheresis in the treatment of dry form of age
      related macular degeneration.
AB  - Purpose. Determining long-term effects of rheohaemapheresis on the dry form of
      age-related macular degeneration. Methods. This study evaluates 19 patients,
      average age of 67.6 years, treated with rheohaemapheresis and 18 patients,
      average age of 72.8 years, comprising the control group. Minimum follow up period
      was 3.5 years. Each treated patient received a series of 8 sessions of
      rheohaemapheresis of 1.5 plasma volumes within 10 weeks. We measured the
      drusenoid pigment epithelium detachment (DPED), best-corrected visual acuity
      (BCVA), electroretinography (ERG), and rheological parameters. Results. In the
      treatment group, the baseline BCVA was 0.74 (0.36-1.0) 95% CI and BCVA after 3.5
      years was 0.79 (0.41-1.0) 95% CI (P = 0.726). In the control group, the baseline
      BCVA was 0.71 (0.15-1.0) 95% CI and BCVA after 3.5 years decreased to 0.7 (0.32
      0.87) 95% CI (P = 0.031). Baseline DPED was 6.78 +/- 3.79 mm(2); after 3.5 years,
      it decreased to 4.13 +/- 3.84 mm(2) (P < 0.001). In the control group, the
      baseline DPED was 4.09 +/- 3.48 mm(2); after 3.5 years, it increased to 6.69 +/-
      4.2 mm(2) (P = 0.001). We noted increasing levels of positive wave peaking at 50
      milliseconds (P50) after treatment (P = 0.022) and a stable amplitude of photopic
      responses of treated patients. Conclusion. Over the long term, rheohaemapheresis
      reduced the DPED, improved the function of photoreceptors, and prevented the
      decline of BCVA. 

PMID- 24455195
TI  - External Dacryocystorhinostomy: Characteristics and Surgical Outcomes in Patients
      with and without Previous Dacryocystitis.
AB  - Objective. To compare pre- and postoperative characteristics and surgical success
      rates of patients with and without previous episodes of dacryocystitis, who
      underwent external dacryocystorhinostomy (DCR) for nasolacrimal duct obstruction
      (NLDO). Methods. The medical files of all patients who underwent external DCR
      between 2006 and 2011 in our institution were reviewed. The retrieved data of
      patients with and without previous episodes of dacryocystitis were compared.
      Surgical success was determined by postoperative followup of at least 6 months.
      Results. A total of 185 patients with NLDO underwent external DCR of whom 152
      (100 females and 52 males, mean age 67 +/- 15 years) met the inclusion criteria.
      Sixty had previous episodes of dacryocystitis and 92 did not. Left-side
      obstruction was more common than right-side obstruction among patients with
      previous episodes of dacryocystitis (48.3% versus 31.7%, resp., P = 0.031).
      Glaucoma patients were significantly more likely to develop dacryocystitis than
      patients without glaucoma (P = 0.002). The success rate of external DCR was 94.4%
      for patients with previous episodes of dacryocystitis and 86.7% for patients
      without (P = 0.337). Conclusions. The surgical outcomes of external DCR in
      patients with or without a previous episode of dacryocystitis were similar.
      Patients with glaucoma and NLDO had a significantly higher risk of developing
      dacryocystitis. 

PMID- 24455196
TI  - Imaging the Anterior Segment: High-Frequency Ultrasound and Anterior Segment OCT.

PMID- 24455197
TI  - Gender and spondyloarthropathy-associated uveitis.
AB  - Spondyloarthropathies encompass a group of inflammatory diseases with arthritis
      and other features such as enthesitis and dermatologic and gastrointestinal
      involvement. Up to 37% of spondyloarthropathy patients may develop uveitis which
      is typically bilateral asynchronous acute anterior uveitis. Spondyloarthropathies
      with and without uveitis are more prevalent among males; the reasons for gender
      imbalance are unclear. This review will focus on gender differences in the
      prevalence, incidence, clinical manifestations, and prognosis of uveitis
      associated with spondyloarthropathies. 

PMID- 24455198
TI  - Effects of age and cardiovascular disease on selective attention.
AB  - In order to study the effect of normal aging and cardiovascular disease on
      selective attention, a letter-identification task was proposed to younger and
      older healthy adults as well as patients with a recent myocardial infarction or a
      recent coronary artery bypass grafting. Participants had to detect either a big
      stimulus or a small one surrounded by flanking letters. The stimuli were
      displayed horizontally, either in the left (LVF) or in the right visual field
      (RVF). The interaction between the type of stimulus and the hemifield of
      presentation reached significance in all groups except in patients who underwent
      a coronary artery bypass. Only young normal adults showed the expected
      significant RVF advantage when detecting big stimuli and an LVF advantage when
      detecting small stimuli surrounded by flankers. In older control adults and in
      patients with myocardial infarction, the RVF advantage for the condition with
      selective attention vanished. In patients who underwent a coronary artery bypass,
      reaction times were increased and no hemispheric specialization for selective
      attention emerged. The results are discussed with regard to the hypothesis of a
      Hemispheric Asymmetry Reduction in Older Adults (HAROLD model) and to the
      presence of cognitive dysfunction consecutive to cardiovascular disease. 

PMID- 24455199
TI  - Risk of mortality (including sudden cardiac death) and major cardiovascular
      events in atypical and typical antipsychotic users: a study with the general
      practice research database.
AB  - Objective. Antipsychotics have been associated with increased cardiac events
      including mortality. This study assessed cardiac events including mortality among
      antipsychotic users relative to nonusers. Methods. The General Practice Research
      Database (GPRD) was used to identify antipsychotic users, matched general
      population controls, and psychiatric diseased nonusers. Outcomes included cardiac
      mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide),
      coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity
      analyses were conducted for age, dose, duration, antipsychotic type, and
      psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and
      67,901 atypical), 544,726 general population controls, and 193,920 psychiatric
      nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar
      disorder had increased risks of all-cause mortality compared to general
      population controls, while nonusers with major depression had comparable risks.
      Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause
      mortality in antipsychotic users was 1.75 (95% CI: 1.64-1.87); cardiac mortality
      1.72 (95% CI: 1.42-2.07); SCD primary definition 5.76 (95% CI: 2.90-11.45); SCD
      secondary definition 2.15 (95% CI: 1.64-2.81); CHD 1.16 (95% CI: 0.94-1.44); and
      VA 1.16 (95% CI: 1.02-1.31). aRRs of the various outcomes were lower for atypical
      versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80-0.85);
      cardiac mortality 0.89 (95% CI: 0.82-0.97); and SCD secondary definition 0.76
      (95% CI: 0.55-1.04). Conclusions. Antipsychotic users had an increased risk of
      cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser
      cohort. 

PMID- 24455200
TI  - Cognitive Performance following Carotid Endarterectomy or Stenting in
      Asymptomatic Patients with Severe ICA Stenosis.
AB  - Background. Endarterectomy (CEA) or stenting (CAS) of a stenotic carotid artery
      is currently undertaken to reduce stroke risk. In addition removal of the
      arterial narrowing has been hypothesized to improve cerebral hemodynamics and
      provide benefits in cognitive functions, by supposedly resolving a
      "hypoperfusion" condition. Methods. In this study we sought to test whether
      resolution of a carotid stenosis is followed by measurable changes in cognitive
      functions in 22 subjects with "asymptomatic" stenosis. Results. A main finding of
      the study was the statistically significant pre-post difference observed in the
      performance of phonological verbal fluency and Rey's 15-word immediate recall.
      Remarkably, there was a significant interaction between phonological verbal
      fluency performance and side of the carotid intervention, as the improvement in
      the verbal performance, a typical "lateralized" skill, was associated with
      resolution of the left carotid stenosis. Conclusion. The results reflect a
      substantial equivalence of the overall performance at the before- and after- CEA
      or CAS tests. In two domains, however, the postintervention performance resulted
      improved. The findings support the hypothesis that recanalization of a stenotic
      carotid could improve brain functions by resolving hypothetical "hypoperfusion"
      states, associated with the narrowing of the vessels. 

PMID- 24455201
TI  - Fatty Acid desaturase gene polymorphisms and metabolic measures in schizophrenia
      and bipolar patients taking antipsychotics.
AB  - Atypical antipsychotics have become a common therapeutic option in both
      schizophrenia and bipolar disorder. However, these medications come with a high
      risk of metabolic side effects, particularly dyslipidemia and insulin resistance.
      Therefore, identification of patients who are at increased risk for metabolic
      side effects is of great importance. The genetics of fatty acid metabolism is one
      area of research that may help identify such patients. Therefore, in this present
      study, we aimed to determine the effect of one commonly studied genetic
      polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a
      surrogate measure of insulin resistance and lipid levels in a metabolically high
      risk population of patients largely exposed to atypical antipsychotics. This
      study used a cross-sectional design, fasting blood draws, and genetic analysis to
      investigate associations between polymorphisms, haplotypes, and metabolic
      measures. A total of 320 subjects with schizophrenia (n = 226) or bipolar
      disorder (n = 94) were included in this study. The mean age of the population was
      42.5 years and 45% were male. A significant association between FADS1 and FADS2
      haplotypes was found with insulin resistance while controlling for confounders.
      Further investigation is required to replicate this finding. 

PMID- 24455202
TI  - Transcriptionally Repressive Chromatin Remodelling and CpG Methylation in the
      Presence of Expanded CTG-Repeats at the DM1 Locus.
AB  - An expanded CTG-repeat in the 3' UTR of the DMPK gene is responsible for myotonic
      dystrophy type I (DM1). Somatic and intergenerational instability cause the
      disease to become more severe during life and in subsequent generations. Evidence
      is accumulating that trinucleotide repeat instability and disease progression
      involve aberrant chromatin dynamics. We explored the chromatin environment in
      relation to expanded CTG-repeat tracts in hearts from transgenic mice carrying
      the DM1 locus with different repeat lengths. Using bisulfite sequencing we
      detected abundant CpG methylation in the regions flanking the expanded CTG
      repeat. CpG methylation was postulated to affect CTCF binding but we found that
      CTCF binding is not affected by CTG-repeat length in our transgenic mice. We
      detected significantly decreased DMPK sense and SIX5 transcript expression levels
      in mice with expanded CTG-repeats. Expression of the DM1 antisense transcript was
      barely affected by CTG-repeat expansion. In line with altered gene expression,
      ChIP studies revealed a locally less active chromatin conformation around the
      expanded CTG-repeat, namely, decreased enrichment of active histone mark
      H3K9/14Ac and increased H3K9Me3 enrichment (repressive chromatin mark). We also
      observed binding of PCNA around the repeats, a candidate that could launch
      chromatin remodelling cascades at expanded repeats, ultimately affecting gene
      transcription and repeat instability. 

PMID- 24455203
TI  - Comparative (computational) analysis of the DNA methylation status of
      trinucleotide repeat expansion diseases.
AB  - Previous studies have examined DNA methylation in different trinucleotide repeat
      diseases. We have combined this data and used a pattern searching algorithm to
      identify motifs in the DNA surrounding aberrantly methylated CpGs found in the
      DNA of patients with one of the three trinucleotide repeat (TNR) expansion
      diseases: fragile X syndrome (FRAXA), myotonic dystrophy type I (DM1), or
      Friedreich's ataxia (FRDA). We examined sequences surrounding both the variably
      methylated (VM) CpGs, which are hypermethylated in patients compared with
      unaffected controls, and the nonvariably methylated CpGs which remain either
      always methylated (AM) or never methylated (NM) in both patients and controls.
      Using the J48 algorithm of WEKA analysis, we identified that two patterns are all
      that is necessary to classify our three regions CCGG* which is found in VM and
      not in AM regions and AATT* which distinguished between NM and VM + AM using
      proportional frequency. Furthermore, comparing our software with MEME software,
      we have demonstrated that our software identifies more patterns than MEME in
      these short DNA sequences. Thus, we present evidence that the DNA sequence
      surrounding CpG can influence its susceptibility to be de novo methylated in a
      disease state associated with a trinucleotide repeat. 

PMID- 24455204
TI  - Population-Sequencing as a Biomarker of Burkholderia mallei and Burkholderia
      pseudomallei Evolution through Microbial Forensic Analysis.
AB  - Large-scale genomics projects are identifying biomarkers to detect human disease.
      B. pseudomallei and B. mallei are two closely related select agents that cause
      melioidosis and glanders. Accurate characterization of metagenomic samples is
      dependent on accurate measurements of genetic variation between isolates with
      resolution down to strain level. Often single biomarker sensitivity is augmented
      by use of multiple or panels of biomarkers. In parallel with single biomarker
      validation, advances in DNA sequencing enable analysis of entire genomes in a
      single run: population-sequencing. Potentially, direct sequencing could be used
      to analyze an entire genome to serve as the biomarker for genome identification.
      However, genome variation and population diversity complicate use of direct
      sequencing, as well as differences caused by sample preparation protocols
      including sequencing artifacts and mistakes. As part of a Department of Homeland
      Security program in bacterial forensics, we examined how to implement whole
      genome sequencing (WGS) analysis as a judicially defensible forensic method for
      attributing microbial sample relatedness; and also to determine the strengths and
      limitations of whole genome sequence analysis in a forensics context. Herein, we
      demonstrate use of sequencing to provide genetic characterization of populations:
      direct sequencing of populations. 

PMID- 24455205
TI  - Multipyrene tandem probes for point mutations detection in DNA.
AB  - Here we report design, synthesis and characterization of highly sensitive,
      specific and stable in biological systems fluorescent probes for point mutation
      detection in DNA. The tandems of 3'- and 5'-mono- and bis-pyrene conjugated
      oligo(2'-O-methylribonucleotides), protected by 3'-"inverted" thymidine, were
      constructed and their potential as new instruments for genetic diagnostics was
      studied. Novel probes have been shown to exhibit an ability to form stable
      duplexes with DNA target due to the stabilizing effect of multiple pyrene units
      at the junction. The relationship between fluorescent properties of developed
      probes, the number of pyrene residues at the tandem junction, and the location of
      point mutation has been studied. On the basis of the data obtained, we have
      chosen the probes possessing the highest fluorescence intensity along with the
      best mismatch discrimination and deletion and insertion detection ability.
      Application of developed probes for detection of polymorphism C677T in MTHFR gene
      has been demonstrated on model systems. 

PMID- 24455206
TI  - Incidence of new-onset hypertension in cancer patients: a retrospective cohort
      study.
AB  - This retrospective cohort study was conducted to estimate incidence rates of new
      onset hypertension in adult cancer patients identified from the Varian Medical
      Oncology outpatient database. Incidence rates of increasing levels of
      hypertension severity were calculated overall and for periods of chemotherapy
      exposure and nonexposure. Cox models sought predictors of new-onset hypertension
      severity among baseline and chemotherapy exposure variables. New-onset
      hypertension was observed in about one-third of 25,090 patients with various
      cancer types. The incidence rates (IR) of severe and crisis-level hypertension,
      respectively, were the highest in patients with gastric (18.5 cases per 100
      person-years (PY), 5.6 per 100 PY) and ovarian cancer (20.2 per 100 PY, 4.8 per
      100 PY). The highest IR of moderate hypertension was observed in patients with
      renal cancer (46.7 per 100 PY). Across all cancers, chemotherapy exposure was
      associated with a 2-3.5-fold increase in risk of any degree of hypertension
      compared to periods of no chemotherapy; higher hypertension levels showed greater
      variability in relative risks by type and line of therapy but indicated an
      overall increase associated with chemotherapy exposure. These results help to
      elucidate the factors influencing HTN among cancer patients and the incidence of
      HTN relative to chemotherapy exposure. 

PMID- 24455207
TI  - A Cost-Benefit and Accurate Method for Assessing Microalbuminuria: Single versus
      Frequent Urine Analysis.
AB  - Background. The purpose of this study was to answer the question whether a single
      testing for microalbuminuria results in a reliable conclusion leading costs
      saving. Methods. This current cross-sectional study included a total of 126
      consecutive persons. Microalbuminuria was assessed by collection of two fasting
      random urine specimens on arrival to the clinic as well as one week later in the
      morning. Results. In overall, 17 out of 126 participants suffered from
      microalbuminuria that, among them, 12 subjects were also diagnosed as
      microalbuminuria once assessing this factor with a sensitivity of 70.6%, a
      specificity of 100%, a PPV of 100%, a NPV of 95.6%, and an accuracy of 96.0%. The
      measured sensitivity, specificity, PVV, NPV, and accuracy in hypertensive
      patients were 73.3%, 100%, 100%, 94.8%, and 95.5%, respectively. Also, these
      rates in nonhypertensive groups were 50.0%, 100%, 100%, 97.3%, and 97.4%,
      respectively. According to the ROC curve analysis, a single measurement of UACR
      had a high value for discriminating defected from normal renal function state (c
      = 0.989). Urinary albumin concentration in a single measurement had also high
      discriminative value for diagnosis of damaged kidney (c = 0.995). Conclusion. The
      single testing of both UACR and urine albumin level rather frequent testing leads
      to high diagnostic sensitivity, specificity, and accuracy as well as high
      predictive values in total population and also in hypertensive subgroups. 

PMID- 24455208
TI  - Persistence and progression of masked hypertension: a 5-year prospective study.
AB  - Objectives. To examine masked hypertension persistence over 5 years. Methods.
      White-collar workers were recruited from three public organizations. Blood
      pressure (BP) was measured using Spacelabs 90207. Manually operated BP was
      defined as the mean of the first three readings taken at rest. Ambulatory BP was
      defined as the mean of the next readings taken every 15 minutes and recorded
      during working hours. BP was assessed three times over 5 years. Masked
      hypertension was defined as manually operated BP less than 140 and less than 90
      mmHg and ambulatory BP at least 135 or at least 85 mmHg. Sustained hypertension
      was defined as manually operated BP at least 140 or at least 90 mmHg and
      ambulatory BP at least 135 or at least 85 mmHg or being treated for hypertension.
      Results. BP measurements were obtained from 1669 participants from whom 232 had
      masked hypertension at baseline. Persistence of masked hypertension was 38% and
      18.5%, after 3 and 5 years, respectively. Progression to sustained hypertension
      was 26% and 37%, after 3 and 5 years, respectively. Conclusion. Among baseline
      masked hypertensives, one-third progressed to sustained hypertension and about
      one out of five remained masked after 5 years, potentially delaying diagnosis and
      treatment. 

PMID- 24455209
TI  - Stability of a Lipase Extracted from Seeds of Pachira aquatica in Commercial
      Detergents and Application Tests in Poultry Wastewater Pretreatment and Fat
      Particle Hydrolysis.
AB  - A protein extract containing a plant lipase from oleaginous seeds of Pachira
      aquatica was tested using soybean oil, wastewater from a poultry processing
      plant, and beef fat particles as substrate. The hydrolysis experiments were
      carried out at a temperature of 40 degrees C, an incubation time of 90 minutes,
      and pH 8.0-9.0. The enzyme had the best stability at pH 9.0 and showed good
      stability in the alkaline range. It was found that P. aquatica lipase was stable
      in the presence of some commercial laundry detergent formulations, and it
      retained full activity up to 0.35% in hydrogen peroxide, despite losing activity
      at higher concentrations. Concerning wastewater, the lipase increased free fatty
      acids release by 7.4 times and promoted the hydrolysis of approximately 10% of
      the fats, suggesting that it could be included in a pretreatment stage,
      especially for vegetable oil degradation. 

PMID- 24455210
TI  - Modelling and Optimization Studies on a Novel Lipase Production by Staphylococcus
      arlettae through Submerged Fermentation.
AB  - Microbial enzymes from extremophilic regions such as hot spring serve as an
      important source of various stable and valuable industrial enzymes. The present
      paper encompasses the modeling and optimization approach for production of
      halophilic, solvent, tolerant, and alkaline lipase from Staphylococcus arlettae
      through response surface methodology integrated nature inspired genetic
      algorithm. Response surface model based on central composite design has been
      developed by considering the individual and interaction effects of fermentation
      conditions on lipase production through submerged fermentation. The validated
      input space of response surface model (with R (2) value of 96.6%) has been
      utilized for optimization through genetic algorithm. An optimum lipase yield of
      6.5 U/mL has been obtained using binary coded genetic algorithm predicted
      conditions of 9.39% inoculum with the oil concentration of 10.285% in 2.99 hrs
      using pH of 7.32 at 38.8 degrees C. This outcome could contribute to introducing
      this extremophilic lipase (halophilic, solvent, and tolerant) to industrial
      biotechnology sector and will be a probable choice for different food, detergent,
      chemical, and pharmaceutical industries. The present work also demonstrated the
      feasibility of statistical design tools integration with computational tools for
      optimization of fermentation conditions for maximum lipase production. 

PMID- 24455211
TI  - Immunotherapy of neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is a chronic inflammatory disease of the central
      nervous system that affects the optic nerves and spinal cord resulting in visual
      impairment and myelopathy. There is a growing body of evidence that
      immunotherapeutic agents targeting T and B cell functions, as well as active
      elimination of proinflammatory molecules from the peripheral blood circulation,
      can attenuate disease progression. In this review, we discuss the
      immunotherapeutic options and the treatment strategies in NMO. We also analyze
      the pathogenic mechanisms of the disease in order to provide recommendations
      regarding treatments. 

PMID- 24455212
TI  - A review of adult obesity prevalence, trends, risk factors, and epidemiologic
      methods in Kuwait.
AB  - OBJECTIVE: Kuwait is among the countries with the highest obesity rates
      worldwide; however, little is known about the state of obesity epidemiology
      research in Kuwait. In this paper, we therefore review the findings and
      methodology of studies on the prevalence, trends and risk factors of obesity in
      Kuwait. METHODS: The PubMed database was searched using the keyword combination:
      obesity and adults and Kuwait. Out of 111 articles, 39 remained after abstract
      review, and 18 were selected after full-text review. RESULTS: The studies were
      all cross-sectional and published in the last fifteen years (1997-2012). The
      sample size ranged from 177 to 38,611 individuals. Only 30% of studies used
      random sampling. The prevalence (BMI >= 30) in studies with a nationally
      representative sample ranged from 24% to 48% overall and in adults >50 years was
      greater than 52%. Rates were significantly higher in women than those in men.
      Studies that examined trends showed an increase in obesity prevalence between
      1980 and 2009. Multiple risk factors including sociocultural factors were
      investigated in the studies; however, factors were only crudely assessed.
      CONCLUSION: There is a need for future studies, particularly surveillance surveys
      and prospective cohort studies utilizing advanced methods, to monitor trends and
      to comprehensively assess the factors contributing to the obesity epidemic in
      Kuwait.

PMID- 24455213
TI  - Association of obesity with proteasomal gene polymorphisms in children.
AB  - The aim of this study was to ascertain possible associations between childhood
      obesity, its anthropometric and clinical parameters, and three loci of
      proteasomal genes rs2277460 (PSMA6 c.-110C>A), rs1048990 (PSMA6 c.-8C>G), and
      rs2348071 (PSMA3 c. 543+138G>A) implicated in obesity-related diseases. Obese
      subjects included 94 otherwise healthy children in Latvia. Loci were genotyped
      and then analyzed using polymerase chain reactions, with results compared to
      those of 191 nonobese controls. PSMA3 SNP frequency differences between obese
      children and controls, while not reaching significance, suggested a trend. These
      differences, however, proved highly significant (P < 0.002) in the subset of
      children reporting a family history of obesity. Among obese children denying such
      history, PSMA6 c.-8C>G SNP differences, while being nonsignificant, likewise
      suggested a trend in comparison to the nonobese controls. No PSMA6 c.-110C>A SNP
      differences were detected in the obese group or its subsets. Finally, PSMA3 SNP
      differences were significantly associated (P < 0.05) with circulating low-density
      lipoprotein cholesterol (LDL) levels. Our results clearly implicate the PSMA3
      gene locus as an obesity risk factor in those Latvian children with a family
      history of obesity. While being speculative, the clinical results are suggestive
      of altered circulatory LDL levels playing a possible role in the etiology of
      obesity in the young. 

PMID- 24455214
TI  - The impact of rapid weight loss on oxidative stress markers and the expression of
      the metabolic syndrome in obese individuals.
AB  - OBJECTIVE: Obesity is linked with a state of increased oxidative stress, which
      plays an important role in the etiology of atherosclerosis and type 2 diabetes
      mellitus. The aim of our study was to evaluate the effect of rapid weight loss on
      oxidative stress markers in obese individuals with metabolic syndrome (MetS).
      DESIGN AND METHODS: We measured oxidative stress markers in 40 obese subjects
      with metabolic syndrome (MetS+), 40 obese subjects without metabolic syndrome
      (MetS-), and 20 lean controls (LC) at baseline and after three months of very low
      caloric diet. RESULTS: Oxidized low density lipoprotein (ox-LDL) levels decreased
      by 12% in MetS+ subjects, associated with a reduction in total cholesterol (TC),
      even after adjustment for age and sex. Lipoprotein associated phospholipase A2
      (Lp-PLA2) activity decreased by 4.7% in MetS+ subjects, associated with a drop in
      LDL-cholesterol (LDL-C), TC, and insulin levels. Multivariate logistic regression
      analysis showed that a model including ox-LDL, LpPLA2 activity, and
      myeloperoxidase (MPO) improved prediction of MetS status among obese individuals
      compared to each oxidative stress marker alone. CONCLUSIONS: Oxidative stress
      markers were predictive of MetS in obese subjects, suggesting a higher oxidative
      stress. Rapid weight loss resulted in a decline in oxidative stress markers,
      especially in MetS+ patients.

PMID- 24455215
TI  - Effects of exercise in the treatment of overweight and obese children and
      adolescents: a systematic review of meta-analyses.
AB  - PURPOSE: Conduct a systematic review of previous meta-analyses addressing the
      effects of exercise in the treatment of overweight and obese children and
      adolescents. METHODS: Previous meta-analyses of randomized controlled exercise
      trials that assessed adiposity in overweight and obese children and adolescents
      were included by searching nine electronic databases and cross-referencing from
      retrieved studies. Methodological quality was assessed using the Assessment of
      Multiple Systematic Reviews (AMSTAR) Instrument. The alpha level for statistical
      significance was set at P <= 0.05. RESULTS: Of the 308 studies reviewed, two
      aggregate data meta-analyses representing 14 and 17 studies and 481 and 701 boys
      and girls met all eligibility criteria. Methodological quality was 64% and 73%.
      For both studies, statistically significant reductions in percent body fat were
      observed (P = 0.006 and P < 0.00001). The number-needed-to treat (NNT) was 4 and
      3 with an estimated 24.5 and 31.5 million overweight and obese children in the
      world potentially benefitting, 2.8 and 3.6 million in the US. No other measures
      of adiposity (BMI-related measures, body weight, and central obesity) were
      statistically significant. CONCLUSIONS: Exercise is efficacious for reducing
      percent body fat in overweight and obese children and adolescents. Insufficient
      evidence exists to suggest that exercise reduces other measures of adiposity.

PMID- 24455216
TI  - BMI and an anthropometry-based estimate of fat mass percentage are both valid
      discriminators of cardiometabolic risk: a comparison with DXA and bioimpedance.
AB  - OBJECTIVE: To determine whether categories of obesity based on BMI and an
      anthropometry-based estimate of fat mass percentage (FM% equation) have similar
      discriminative ability for markers of cardiometabolic risk as measurements of FM%
      by dual-energy X-ray absorptiometry (DXA) or bioimpedance analysis (BIA). DESIGN
      AND METHODS: A study of 40-79-year-old male (n = 205) and female (n = 388) Finns.
      Weight, height, blood pressure, triacylglycerols, HDL cholesterol, and fasting
      blood glucose were measured. Body composition was assessed by DXA and BIA and a
      FM%-equation. RESULTS: For grade 1 hypertension, dyslipidaemia, and impaired
      fasting glucose >6.1 mmol/L, the categories of obesity as defined by BMI and the
      FM% equation had 1.9% to 3.7% (P < 0.01) higher discriminative power compared to
      DXA. For grade 2 hypertension the FM% equation discriminated 1.2% (P = 0.05)
      lower than DXA and 2.8% (P < 0.01) lower than BIA. Receiver operation
      characteristics confirmed BIA as best predictor of grade 2 hypertension and the
      FM% equation as best predictor of grade 1 hypertension. All other differences in
      area under curve were small (<=0.04) and 95% confidence intervals included 0.
      CONCLUSIONS: Both BMI and FM% equations may predict cardiometabolic risk with
      similar discriminative ability as FM% measured by DXA or BIA.

PMID- 24455217
TI  - Hyperleptinemia, adiposity, and risk of metabolic syndrome in older adults.
AB  - Background. Abdominal adiposity and serum leptin increase with age as does risk
      of metabolic syndrome. This study investigates the prospective association
      between leptin and metabolic syndrome risk in relation to adiposity and
      cytokines. Methods. The Health, Aging, and Body Composition study is a
      prospective cohort of older adults aged 70 to 79 years. Baseline measurements
      included leptin, cytokines, BMI, total percent fat, and visceral and subcutaneous
      fat. Multivariate logistic regression was used to determine the association
      between leptin and metabolic syndrome (defined per NCEP ATP III) incidence after
      6 years of follow-up among 1,120 men and women. Results. Leptin predicted
      metabolic syndrome in men (P for trend = 0.0002) and women (P for trend =
      0.0001). In women, risk of metabolic syndrome increased with higher levels of
      leptin (compared with quintile 1, quintile 2 RR = 3.29, CI = 1.36, 7.95; quintile
      3 RR = 3.25, CI = 1.33, 7.93; quintile 4 RR = 5.21, CI = 2.16, 12.56; and
      quintile 5 RR = 7.97, CI = 3.30, 19.24) after adjusting for potential
      confounders. Leptin remained independently associated with metabolic syndrome
      risk after additional adjustment for adiposity, cytokines, and CRP. Among men,
      this association was no longer significant after controlling for adiposity.
      Conclusion. Among older women, elevated concentrations of leptin may increase the
      risk of metabolic syndrome independent of adiposity and cytokines. 

PMID- 24455218
TI  - Dietary Diversity and Meal Frequency Practices among Infant and Young Children
      Aged 6-23 Months in Ethiopia: A Secondary Analysis of Ethiopian Demographic and
      Health Survey 2011.
AB  - Background. Appropriate complementary feeding practice is essential for growth
      and development of children. This study aimed to assess dietary diversity and
      meal frequency practice of infants and young children in Ethiopia. Methods. Data
      collected in the Ethiopian Demographic and Health Survey (EDHS) from December
      2010 to June 2011 were used for this study. Data collected were extracted,
      arranged, recoded, and analyzed by using SPSS version 17. A total of 2836
      children aged 6-23 months were used for final analysis. Both bivariate and
      multivariate analysis were done to identify predictors of feeding practices.
      Result. Children with adequate dietary diversity score and meal frequency were
      10.8% and 44.7%, respectively. Children born from the richest households showed
      better dietary diversity score (OR = 0.256). Number of children whose age less
      than five years was important predictor of dietary diversity (OR = 0.690).
      Mothers who had exposure to media were more likely to give adequate meal
      frequency to their children (OR = 0.707). Conclusion. Dietary diversity and meal
      frequency practices were inadequate in Ethiopia. Wealth quintile, exposure to
      media, and number of children were affecting feeding practices. Improving
      economic status, a habit of eating together, and exposure to media are important
      to improve infant feeding practices in Ethiopia. 

PMID- 24455219
TI  - The Effect of a Maternal Double Megadose of Vitamin A Supplement on Serum Levels
      of Retinol in Children Aged under Six Months.
AB  - Objective. To measure concentrations of serum retinol in children after the use
      of maternal vitamin A double megadose supplements. Design. Randomized controlled
      clinical trial. Setting. The study was conducted at two maternity hospitals in
      the city of Recife, in the northeast region of Brazil between August 2007 and
      June 2009. Subjects and Methods. 276 children/mothers were recruited after birth
      and the women received a 200,000 IU capsule of vitamin A. After ten days they
      were randomly assigned to two treatment groups. One group received a second
      200.000 IU capsule, while the other received a placebo. The concentrations of
      retinol in the serum of the children from each group were measured at 2, 4, and 6
      months. Results. 173 children completed the study. There was no difference
      between the two treatment groups (P = 0.514). The mean base retinol level was
      lower than that at four and six months (P < 0.001). Conclusions. The maternal
      double megadose supplement had no additional effect on the serum retinol levels
      of the children, although concentrations of retinol in the children rose in the
      first six months of life. This trial is registered with NCT00742937. 

PMID- 24455220
TI  - Successful Integration of Hepatitis C Virus Point-of-Care Tests into the Denver
      Metro Health Clinic.
AB  - Background. The Centers for Disease Control and Prevention (CDC) recommends
      testing and linkage to care for persons most likely infected with hepatitis C
      virus (HCV), including persons with human immunodeficiency virus. We explored
      facilitators and barriers to integrating HCV point-of-care (POC) testing into
      standard operations at an urban STD clinic. Methods. The OraQuick HCV rapid
      antibody test was integrated at the Denver Metro Health Clinic (DMHC). All
      clients with at least one risk factor were offered the POC test. Research staff
      conducted interviews with clients (three HCV positive and nine HCV negative).
      Focus groups were conducted with triage staff, providers, and linkage-to-care
      counselors. Results. Clients were pleased with the ease of use and rapid return
      of results from the HCV POC test. Integrating the test into this setting required
      more time but was not overly burdensome. While counseling messages were clear to
      staff, clients retained little knowledge of hepatitis C infection or factors
      related to risk. Barriers to integrating the HCV POC test into clinic operations
      were loss to follow-up and access to care. Conclusion. DMHC successfully
      integrated HCV POC testing and piloted a HCV linkage-to-care program. Providing
      testing opportunities at STD clinics could increase identification of persons
      with HCV infection. 

PMID- 24455221
TI  - Attitudes towards and Beliefs about HIV Testing among Latino Immigrant MSM: A
      Comparison of Testers and Nontesters.
AB  - Latino immigrant men who have sex with men (MSM) are at risk for HIV and delayed
      diagnosis. An exploratory study using qualitative interviews that assess the
      beliefs and attitudes of 54 Latino immigrant MSM in Seattle, Washington, is
      presented. The goal of this research is to determine whether attitudinal
      differences exist between participants who had and had not been tested and to use
      any insight into the development of a media campaign to promote testing. Over one
      third of the men have never been tested for HIV. Nontesters are more likely to be
      men who have sex with men and women, have less knowledge about HIV risks,
      perceive their sexual behaviors as less risky, and deflect HIV-related stigma.
      Testers are more likely to be self-identified as being gays. Both groups believe
      that fear of a positive result is the main barrier to testing. Both groups
      believe that family members have negative attitudes towards HIV testing and that
      having Latino staff at HIV testing sites hinders confidentiality. Financial
      concerns with regard to the cost of testing were also expressed by both groups.
      Based on these insights, recommended strategies for the development of HIV
      prevention and testing campaigns are made. 

PMID- 24455222
TI  - Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican
      HIV Patients Who Did or Did Not Receive Antiretroviral Therapy.
AB  - Introduction. Objective and subjective alterations related to salivary flow have
      been reported in patients infected with human immunodeficiency virus (HIV), and
      these alterations are associated with the introduction of antiretroviral therapy.
      The aim of the current study was to discern whether these alterations are disease
      induced or secondary to drug therapy. Objective. The objective was to determine
      the relationships between low salivary flow, xerostomia, and flavor alterations
      in HIV patients who did or did not receive antiretroviral therapy. Materials and
      Methods. In this cross-sectional study, HIV patients were divided into two groups
      based on whether they had received antiretroviral therapy. Those patients with a
      previous diagnosis of any salivary gland disease were excluded. A survey was used
      to assess subjective variables, and colorimetry and salivary flow rates were
      measured using the Schirmer global test. Results. A total of 293 patients were
      included. The therapy group showed a significantly lower average salivary flow
      than did the group without therapy, and we observed that the flow rate tended to
      decrease after one year of therapy. The results were not conclusive, despite
      significant differences in xerostomia and flavor alteration between the groups.
      Conclusion. The study results suggest that antiretroviral therapy can cause
      cumulative damage that affects the amount of salivary flow. 

PMID- 24455223
TI  - Iron Deficiency Anemia among Hospitalized Children in Konya, Turkey.
AB  - The aim of this study was to investigate the characteristics of our hospitalized
      patients with the diagnosis of iron deficiency anemia (IDA) and effects of the
      IDA prevention project of the Turkish Ministry of Health which was started in
      2004. The recommended dose of prophylactic iron supplementation was 1-2
      mg/kg/day. The files of 1519 patients who were hospitalized to Konya Education
      and Research Hospital Pediatrics Clinic were reviewed. A total of 50 patients
      consisting of 35 boys and 15 girls with the mean age of 16,59 +/- 1,68 months
      were included into the study. The prevalence of IDA was 3.29% (boys: 4.23%,
      girls: 2.1%). Hgb and Hct of the patients >24 months were significantly higher
      than those of the patients with the age of 6-12 months. Iron supplementation
      receiving rates were very low. Of the 28 patients older than 12 months, only 44%
      of them had received a full course of iron supplementation for 8 months. In
      conclusion, although prophylactic iron supplementation lowered the prevalences of
      IDA, receiving rates of iron supplementation were not adequate. While IDA is
      still a public health problem, prophylactic approaches should be carried out more
      effectively. 

PMID- 24455224
TI  - Is vitamin d insufficiency associated with mortality of critically ill patients?
AB  - Objective. To evaluate the vitamin D status of our critically ill patients and
      its relevance to mortality. Patients and Methods. We performed a prospective
      observational study in the medical intensive care unit of a university hospital
      between October 2009 and March 2011. Vitamin D levels were measured and
      insufficiency was defined as <20 ng/mL. Results. Two hundred and one patients
      were included in the study. The median age was 66 (56-77) and the majority of
      patients were male (56%). The median serum level of vitamin D was 14,9 ng/mL and
      139 (69%) patients were vitamin D insufficient on admission. While we grouped the
      ICU patients as vitamin D insufficient and sufficient, vitamin D insufficient
      patients had more severe acute diseases and worse laboratory values on admission.
      These patients had more morbidities and were exposed to more invasive therapies
      during stay. The mortality rate was significantly higher in the vitamin D
      insufficient group compared to the vitamin D sufficient group (43% versus 26%, P
      = 0,027). However, logistic regression analysis demonstrated that vitamin D
      insufficiency was not an independent risk factor for mortality. Conclusion.
      Vitamin D insufficiency is common in our critically ill patients (69%), but it is
      not an independent risk factor for mortality. 

PMID- 24455225
TI  - Temperament, Character, and Depressive Symptoms during Pregnancy: A Study of a
      Japanese Population.
AB  - Background. To examine the effects of temperament and character domains on
      depression during pregnancy. Methods. We examined 601 pregnant women using a
      questionnaire that included the Edinburgh Postnatal Depression Scale (EPDS), the
      Temperament and Character Inventory (TCI), and demographic variables. Results. In
      a hierarchical regression analysis, severity of depression during pregnancy was
      predicted by the women's negative response towards the current pregnancy, low
      self-directedness, and high harm avoidance, persistence, and self-transcendence.
      Conclusion. Depression during pregnancy is predicted by personality traits as
      well as women's negative attitudes towards the current pregnancy. 

PMID- 24455226
TI  - Suicidal Career in Severe Depression among Long-Term Survivors: In a Followup
      after 37-53 Years Suicide Attempts Appeared to End Long before Depression.
AB  - Objective. To describe the suicidal career in the long-term course of severe
      depression. Subjects and Method. Seventy-five former in-patients were interviewed
      by telephone about course of depression and suicide attempts 37-53 years after
      index admission. Medical records were read in many cases. Results. 29 subjects
      had attempted suicide, 13 repeated, 10 made severe, and 13 violent attempts. The
      risk of suicide attempt decreased by 10% for every decade spent depressed.
      Suicide attempts were made early in course of depression, and more time was spent
      depressed after suicide attempts than before. Conclusions. A healing process of
      the suicidal career, which may occur long before the end of the last depressive
      episode (sometimes decades), is proposed. 

PMID- 24455227
TI  - Transforming Growth Factor- beta 1 Gene Polymorphism (T29C) in Egyptian Patients
      with Hepatitis B Virus Infection: A Preliminary Study.
AB  - The interindividual variations in the capacity of transforming growth factor-
      beta 1 (TGF- beta 1) production have been ascribed to genetic polymorphisms in
      TGF- beta 1 gene. As pathogenesis of HBV has a genetic background, this
      preliminary study was designed to assess the impact of TGF- beta 1 (T29C) on the
      susceptibility of Egyptians to HBV infection. Genotyping was performed using
      single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian
      hepatitis B patients and 50 healthy controls. TGF- beta 1 plasma levels were
      measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC
      genotype was significantly higher (P < 0.05) in HBV patients compared to
      controls. On the contrary, TC genotype did not show significant difference in
      both groups. TT genotype was significantly higher (P < 0.01) in controls than HBV
      patients. Our current preliminary data revealed that the frequency of the
      genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the
      patients group was out of HWE (P < 0.01). TGF- beta 1 was significantly (r = 
      0.684; P < 0.001) deceased in the sera of patients as compared to normal
      subjects. Depending on our preliminary work, CC genotype may act as a host
      genetic factor in the susceptibility to HBV infection in Egyptians. Taken
      together, the current data pointed to the importance of polymorphism of TGF- beta
      1 gene (T29C) in HBV infection. 

PMID- 24455228
TI  - Diaphragmatic peritonectomy versus full thickness diaphragmatic resection and
      pleurectomy during cytoreduction in patients with ovarian cancer.
AB  - OBJECTIVES: Compare the surgical morbidity of diaphragmatic peritonectomy versus
      full thickness diaphragmatic resection with pleurectomy at radical debulking.
      DESIGN: Prospective cohort study at the Oxford University Hospital. METHODS: All
      debulking with diaphragmatic peritonectomy and/or full thickness resection with
      pleurectomy in the period from April 2009 to March 2012 were part of the study.
      Analysis is focused on the intra- and postoperative morbidity. RESULTS: 42
      patients were eligible for the study, 21 underwent diaphragmatic peritonectomy
      (DP, group 1) and 21 diaphragmatic full thickness resection (DR, group 2). Forty
      patients out of 42 (93%) had complete tumour resection with no residual disease.
      Histology confirmed the presence of cancer in diaphragmatic peritoneum of 19
      patients out of 21 in group 1 and all 21 patients of group 2. Overall
      complications rate was 19% in group 1 versus 33% in group 2. Pleural effusion
      rate was 9.5% versus 14.5% and pneumothorax rate was 14.5% only in group 2. Two
      patients in each group required postoperative chest drains (9.5%). CONCLUSIONS:
      Diaphragmatic surgery is an effective methods to treat carcinomatosis of the
      diaphragm. Patients in the pleurectomy group experienced pneumothorax and a
      higher rate of pleural effusion, but none had long-term morbidity or additional
      surgical interventions.

PMID- 24455230
TI  - Epigenetics in research and practice.

PMID- 24455229
TI  - Evaluating symptoms to improve quality of life in patients with chronic stable
      angina.
AB  - Chronic stable angina (CSA) is a significant problem in the United States that
      can negatively impact patient quality of life (QoL). An accurate assessment of
      the severity of a patient's angina, the impact on their functional status, and
      their risk of cardiovascular complications is key to successful treatment of CSA.
      Active communication between the patient and their healthcare provider is
      necessary to ensure that patients receive optimal therapy. Healthcare providers
      should be aware of atypical symptoms of CSA in their patients, as patients may
      continue to suffer from angina despite the availability of multiple therapies.
      Patient questionnaires and symptom checklists can help patients communicate
      proactively with their healthcare providers. This paper discusses the prevalence
      of CSA, its impact on QoL, and the tools that healthcare providers can use to
      assess the severity of their patients' angina and the impact on QoL. 

PMID- 24455231
TI  - From the idea to its realization: the evolution of minimally invasive techniques
      in neurosurgery.
AB  - Minimally invasive techniques in neurosurgery evolved in two steps. Many
      minimally invasive concepts like neuronavigation, endoscopy, or frame based
      stereotaxy were developed by the pioneers of neurosurgery, but it took decades
      till further technical developments made the realization and broad clinical
      application of these early ideas safe and possible. This thesis will be
      demonstrated by giving examples of the evolution of four minimally invasive
      techiques: neuronavigation, transsphenoidal pituitary surgery, neuroendoscopy and
      stereotaxy. The reasons for their early failure and also the crucial steps for
      the rediscovery of these minimally invasive techniques will be analysed. In the
      80th of the 20th century endoscopy became increasingly applied in different
      surgical fields. The abdominal surgeons coined as first for their endoscopic
      procedures the term minimally invasive surgery in contrast to open surgery. In
      neurrosurgery the term minimally invasive surgery stood not in opposiotion to
      open procedures but was understood as a general concept and philosophy using the
      modern technology such as neuronavigation, endoscopy and planing computer
      workstations with the aim to make the procedures less traumatic. 

PMID- 24455232
TI  - Endoscopic transforaminal thoracic foraminotomy and discectomy for the treatment
      of thoracic disc herniation.
AB  - Thoracic disc herniation is a relatively rare yet challenging-to-diagnose
      condition. Currently there is no universally accepted optimal surgical treatment
      for symptomatic thoracic disc herniation. Previously reported surgical approaches
      are often associated with high complication rates. Here we describe our minimally
      invasive technique of removing thoracic disc herniation, and report the primary
      results of a series of cases. Between January 2009 and March 2012, 13 patients
      with symptomatic thoracic disc herniation were treated with endoscopic thoracic
      foraminotomy and discectomy under local anesthesia. A bone shaver was used to
      undercut the facet and rib head for foraminotomy. Discectomy was achieved by
      using grasper, radiofrequency, and the Holmium-YAG laser. We analyzed the
      clinical outcomes of the patients using the visual analogue scale (VAS), MacNab
      classification, and Oswestry disability index (ODI). At the final follow up
      (mean: 17 months; range: 6-41 months), patient self-reported satisfactory rate
      was 76.9%. The mean VAS for mid back pain was improved from 9.1 to 4.2, and the
      mean ODI was improved from 61.0 to 43.8. One complication of postoperative spinal
      headache occurred during the surgery and the patient was successfully treated
      with epidural blood patch. No other complications were observed or reported
      during and after the surgery. 

PMID- 24455233
TI  - Minimally invasive treatment of the thoracic spine disease: completely
      percutaneous and hybrid approaches.
AB  - The aim of the study was to evaluate the feasibility of a limited invasive
      approach for the treatment of upper thoracic spine disease. Seven patients with
      type-A thoracic fractures and three with tumors underwent long thoracic
      stabilization through a minimally invasive approach. Four patients underwent a
      completely percutaneous approach while the other three underwent a modified
      hybrid technique, a combination of percutaneous and open approach. The hybrid
      constructs were realized using a percutaneous approach to the spine distally to
      the spinal lesion and by open approach proximally. In two patients, the
      stabilization was extended proximally up to the cervical spine. Clinical and
      radiographic assessment was performed during the first year after the operation
      at 3, 6, and 12 months. No technically related complications were seen. The
      postoperative recovery was rapid even in the tumor patients with neurologic
      impairment. Blood loss was irrelevant. At one-year follow-up there was no
      loosening or breakage of the screws or failure of the implants. When technically
      feasible a completely percutaneous approach has to be taken in consideration;
      otherwise, a combined open-percutaneous approach could be planned to minimize the
      invasivity of a completely open approach to the thoracic spine. 

PMID- 24455234
TI  - Burn injuries resulting from hot water bottle use: a retrospective review of
      cases presenting to a regional burns unit in the United kingdom.
AB  - Introduction. Hot water bottles are commonly used to relieve pain and for warmth
      during the colder months of the year. However, they pose a risk of serious burn
      injuries. The aim of this study is to retrospectively review all burn injuries
      caused by hot water bottles presenting to our regional burns unit. Methods.
      Patients with burns injuries resulting from hot water bottle use were identified
      from our burns database between the periods of January 2004 and March 2013 and
      their cases notes reviewed retrospectively. Results. Identified cases involved 39
      children (aged 17 years or younger) and 46 adults (aged 18 years or older). The
      majority of burns were scald injuries. The mean %TBSA was 3.07% (SD +/- 3.40).
      Seven patients (8.24%) required debridement and skin grafting while 3 (3.60%)
      required debridement and application of Biobrane. One patient (1.18%) required
      local flap reconstruction. Spontaneous rupture accounted for 48.20% of injuries
      while accidental spilling and contact accounted for 33% and 18.80% of injuries,
      respectively. The mean time to heal was 28.87 days (SD +/- 21.60). Conclusions.
      This study highlights the typical distribution of hot water bottle burns and the
      high rate of spontaneous rupture of hot water bottles, which have the potential
      for significant burn injuries. 

PMID- 24455236
TI  - Biomarkers of Coagulation and Fibrinolysis during Cemented Total Hip Arthroplasty
      with Pre- versus Postoperative Start of Thromboprophylaxis.
AB  - Venous thrombosis is common in elective hip surgery, and prophylaxis is
      recommended. Clinical trials suggest that the drug dose and timing of initiating
      prophylaxis significantly influence antithrombotic effectiveness and safety. We
      studied the time course and gradient of plasma coagulation and fibrinolysis
      during total hip arthroplasty (THA) in twenty patients that were randomly
      assigned to have the first dose of 5000 IU dalteparin subcutaneously (sc)
      injected 12 hours before or 6 hours after surgery. Baseline characteristics were
      similar in both groups. Specific biomarkers on coagulation (prothrombin fragment
      1+2 (F1+2)) and fibrinolytic activity (plasmin/ alpha 2-antiplasmin complex (PAP)
      and D-dimer) were collected at six events during hospitalization and analysed.
      There were no significant group differences in the biomarkers at any time point.
      The highest concentrations were measured 6 hours after surgery and before the
      first postoperative injection. A marked decrease followed at the first
      postoperative day, and then a second increase in plasma concentrations was
      observed 6 days after surgery. This study showed that activation of coagulation
      and fibrinolysis by the operative trauma was the same when the first dose of
      dalteparin was injected 12 hours before or 6 hours after surgery. 

PMID- 24455235
TI  - The role of thrombophilia in pregnancy.
AB  - Thrombotic disease is a major cause of peripartum morbidity and mortality
      worldwide. Development of thrombosis in pregnancy is multifactorial due to the
      physiologic changes of pregnancy-which induce a relative hypercoagulable state-as
      well as physical changes leading to increased stasis and also the effects of both
      the inherited and the acquired thrombophilias. In this review, we discuss the
      impact of each of these factors on the development of thrombosis as well as the
      evidence for the impact of pregnancy-associated thrombosis on pregnancy outcome.
      We then discuss the use of both prophylactic and therapeutic anticoagulation
      during pregnancy and the puerperium. We review the indications and dosing
      recommendations for administration of anticoagulation in a context of discussing
      the evidence including the lack of evidence and formal guidelines in this area.
      We briefly address the role of the new oral anticoagulants in pregnancy and
      conclude that significant further research in women with thrombophilias and
      pregnancy-associated thrombosis may help clarify the management of this condition
      in the future. 

PMID- 24455237
TI  - Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular
      Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups.
AB  - Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban)
      have become available as an alternative to warfarin anticoagulation in non
      valvular atrial fibrillation (NVAF). Methods. MEDLINE and CENTRAL, regulatory
      agencies websites, clinical trials registers and conference proceedings were
      searched to identify randomised controlled trials of NOAC versus warfarin in
      NVAF. Two investigators reviewed all studies and extracted data on patient and
      study characteristics along with cardiovascular outcomes. Relative risks (RR) and
      95% confidence intervals (CI) were estimated using a random effect meta-analysis.
      Results. Three clinical trials in 50,578 patients were included. The risk of non
      hemorrhagic stroke and systemic embolic events (SEE) was similar with the NOAC
      and warfarin (RR = 0.93; 95% CI = 0.83-1.04), while the risk of intracranial
      bleeding (ICB) with the NOAC was lower than with warfarin (RR = 0.46; 95% CI =
      0.33-0.65). We found differences in the effect size on all strokes and SEE
      depending on geographic region as well as on non-hemorrhagic stroke, SEE,
      bleeding and mortality depending on time in therapeutic range. Conclusion. The
      NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke
      and SEE in the overall NVAF population, but are generally associated with a lower
      risk of ICB than warfarin. 

PMID- 24455238
TI  - TextTB: A Mixed Method Pilot Study Evaluating Acceptance, Feasibility, and
      Exploring Initial Efficacy of a Text Messaging Intervention to Support TB
      Treatment Adherence.
AB  - Objective. To assess a text messaging intervention to promote tuberculosis (TB)
      treatment adherence. Methods. A mixed-methods pilot study was conducted within a
      public pulmonary-specialized hospital in Argentina. Patients newly diagnosed with
      TB who were 18 or older, and had mobile phone access were recruited and
      randomized to usual care plus either medication calendar (n = 19) or text
      messaging intervention (n = 18) for the first two months of treatment. Primary
      outcomes were feasibility and acceptability; secondary outcomes explored initial
      efficacy. Results. Feasibility was evidenced by high access to mobile phones,
      familiarity with texting, most phones limited to basic features, a low rate of
      participant refusal, and many describing suboptimal TB understanding.
      Acceptability was evidenced by participants indicating feeling cared for,
      supported, responsible for their treatment, and many self-reporting adherence
      without a reminder. Participants in the texting group self-reported adherence on
      average 77% of the days whereas only 53% in calendar group returned diaries.
      Exploring initial efficacy, microscopy testing was low and treatment outcomes
      were similar in both groups. Conclusion. The texting intervention was well
      accepted and feasible with greater reporting of adherence using text messaging
      than the diary. Further evaluation of the texting intervention is warranted. 

PMID- 24455239
TI  - Nontuberculous mycobacteria in guadeloupe, martinique, and French Guiana from
      1994 to 2012.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms able to
      cause severe opportunistic human infections. Their distribution patterns are
      subject to geographical variations. This study describes their isolation
      frequencies from clinical specimen in the three French overseas departments of
      the Americas, namely, Guadeloupe, Martinique, and French Guiana during 1994-2012.
      A total of 651 strains from as many patients (one isolate per species per
      patient) were analysed regarding regional isolation patterns and potential
      pattern changes over time. The Mycobacterium avium complex was the most common
      group of NTM in Guadeloupe and French Guiana. In Martinique it was the second
      most common after the rapidly growing mycobacteria. M. fortuitum was the most
      commonly isolated species in all three departments. Some species (M. kansasii, M.
      xenopi, and M. terrae complex) displayed a clear regional preference. Furthermore
      a change in isolation frequency was observed for M. intracellulare (increase) and
      M. kansasii (decrease) in Guadeloupe. In conclusion, marked regional differences
      in isolation frequencies of NTM species were observed in the study area. Results
      are discussed in context of variables such as study populations, risk factors,
      methodology employed, isolation from pulmonary versus sterile isolation sites
      (blood, urine, and CSF), and in vitro drug-susceptibility patterns. 

PMID- 24455240
TI  - Phenotyping chronic pelvic pain based on latent class modeling of physical
      examination.
AB  - Introduction. Defining clinical phenotypes based on physical examination is
      required for clarifying heterogeneous disorders such as chronic pelvic pain
      (CPP). The objective of this study was to determine the number of classes within
      4 examinable regions and then establish threshold and optimal exam criteria for
      the classes discovered. Methods. A total of 476 patients meeting the criteria for
      CPP were examined using pain pressure threshold (PPT) algometry and standardized
      numeric scale (NRS) pain ratings at 30 distinct sites over 4 pelvic regions.
      Exploratory factor analysis, latent profile analysis, and ROC curves were then
      used to identify classes, optimal examination points, and threshold scores.
      Results. Latent profile analysis produced two classes for each region: high and
      low pain groups. The optimal examination sites (and high pain minimum thresholds)
      were for the abdominal wall region: the pair at the midabdomen (PPT threshold
      depression of > 2); vulvar vestibule region: 10:00 position (NRS > 2); pelvic
      floor region: puborectalis (combined NRS > 6); vaginal apex region: uterosacral
      ligaments (combined NRS > 8). Conclusion. Physical examination scores of patients
      with CPP are best categorized into two classes: high pain and low pain.
      Standardization of the physical examination in CPP provides both researchers and
      general gynecologists with a validated technique. 

PMID- 24455241
TI  - Region-Based Partial Volume Correction Techniques for PET Imaging: Sinogram
      Implementation and Robustness.
AB  - Background/Purpose. Limited spatial resolution of positron emission tomography
      (PET) requires partial volume correction (PVC). Region-based PVC methods are
      based on geometric transfer matrix implemented either in image-space (GTM) or
      sinogram-space (GTMo), both with similar performance. Although GTMo is slower, it
      more closely simulates the 3D PET image acquisition, accounts for local
      variations of point spread function, and can be implemented for iterative
      reconstructions. A recent image-based symmetric GTM (sGTM) has shown improvement
      in noise characteristics and robustness to misregistration over GTM. This study
      implements the sGTM method in sinogram space (sGTMo), validates it, and evaluates
      its performance. Methods. Two 3D sphere and brain digital phantoms and a physical
      sphere phantom were used. All four region-based PVC methods (GTM, GTMo, sGTM, and
      sGTMo) were implemented and their performance was evaluated. Results. All four
      PVC methods had similar accuracies. Both noise propagation and robustness of the
      sGTMo method were similar to those of sGTM method while they were better than
      those of GTMo method especially for smaller objects. Conclusion. The sGTMo was
      implemented and validated. The performance of the sGTMo in terms of noise
      characteristics and robustness to misregistration is similar to that of the sGTM
      method and improved compared to the GTMo method. 

PMID- 24455242
TI  - What Is the Clinical Significance of FDG Unexpected Uptake in the Prostate in
      Patients Undergoing PET/CT for Other Malignancies?
AB  - Purpose. To determine the clinical significance of unexpected, abnormal FDG
      uptake in the prostate in patients undergoing FDG-PET/CT for staging of other
      primary malignancies without a prior history of prostate carcinoma. Methods.
      Retrospective search of FDG-PET/CT studies to identify patients with unexpected,
      abnormal FDG uptake in the prostate gland, who underwent subsequent biopsy, was
      performed. 26 patients were identified. Images were reviewed to determine the
      pattern of uptake within the prostate (focal or diffuse) and maximum standardized
      uptake value (SUVmax). PSA and Gleason scores were recorded. Results. 15/26 (58%)
      patients were found to have prostate carcinoma. Gleason scores ranged from 6 to
      9.9. There was no statistical difference in the pattern of uptake (focal versus
      diffuse) or the SUVmax. Serum PSA levels with cancer (range, 2-26.8 ng; mean,
      10.2 ng) and those without cancer (range, 2-10.5 ng; mean, 2.2 ng) were
      statistically significant (P < 0.007, Wilcoxon rank sum test). Conclusions.
      Patients with abnormal uptake in the prostate have a 58% likelihood of occult
      prostate cancer. In the setting of elevated serum PSA levels, abnormal prostate
      uptake should therefore be viewed with suspicion and a urology consult should be
      obtained; however, it is irrelevant in patients with underlying aggressive
      malignancies. 

PMID- 24455243
TI  - Upregulation of voltage-gated calcium channel cav1.3 in bovine somatotropes
      treated with ghrelin.
AB  - Activation of the growth hormone (GH) secretagogue receptor (GHS-R) by synthetic
      GH releasing peptides (GHRP) or its endogenous ligand (Ghrelin) stimulates GH
      release. Though much is known about the signal transduction underlying short-term
      regulation, there is far less information on the mechanisms that produce long
      term effects. In the current report, using an enzyme-linked immunosorbent assay
      for GH detection and whole-cell patch-clamp recordings, we assessed the long-term
      actions of such regulatory factors on voltage-activated Ca(2+) currents in bovine
      somatotropes (BS) separated on a Percoll gradient and detected by
      immunohistochemistry. After 24 h of treatment with Ghrelin (10 nM) or GHRP-6 (100
      nM) enhanced BS secretory activity; GH secretion stimulated by GHS through the
      activation of GHS-R because treatment with the antagonist of GHS-R (D-Lys3-GHRP
      6, 10 MUM) blocked the GH secretion, and the effect was dose and time dependent
      (24, 48, and 72 h). GH secretion stimulated by GHRP-6 was abolished by nifedipine
      (0.5 MUM), a blocker of L-type HVA Ca(2+) channels, and KN-62 (10 MUM), an
      inhibitor of Ca(2+)/CaM-KII. After 72 h in culture, all recorded BS exhibited two
      main Ca(2+) currents: a low voltage-activated (LVA; T-type) and a high voltage
      activated (HVA; mostly dihydropyridine-sensitive L-type) current. Interestingly,
      HVA and LVA channels were differentially upregulated by Ghrelin. Chronic
      treatment with the GHS induced a significant selective increase on the Ba(2+)
      current through HVA Ca(2+) channels, and caused only a small increase of currents
      through LVA channels. The stimulatory effect on HVA current density was
      accompanied by an augment in maximal conductance with no apparent changes in the
      kinetics and the voltage dependence of the Ca(2+) currents, suggesting an
      increase in the number of functional channels in the cell membrane. Lastly, in
      consistency with the functional data, quantitative real-time RT-PCR revealed
      transcripts encoding for the Cav1.2 and Cav1.3 pore-forming subunits of L-type
      channels. The treatment with Ghrelin significantly increased the Cav1.3 subunit
      expression, suggeting that the chronic stimulation of the GHS receptor with
      Ghrelin or GHRP-6 increases the number of voltage-gated Ca(2+) channels at the
      cell surface of BS. 

PMID- 24455244
TI  - The pattern of respiratory disease morbidity and mortality in a tertiary hospital
      in southern-eastern Nigeria.
AB  - Background. Respiratory complaints are commonly encountered in medicine and
      respiratory diseases place a high burden on healthcare infrastructure. Healthcare
      planning should be based on adequate information: this study will help us to
      analyze the pattern of respiratory disease admissions in the medical wards in a
      developing country. Methods. The medical records of patients admitted into the
      medical wards over a 5-year period were retrieved and reviewed. Information
      obtained included demography, diagnosis, comorbid conditions, and risk factors
      for respiratory disease. Results. Three thousand four hundred and ninety patients
      were admitted into the medical wards with 325 (9.3%) of them diagnosed with a
      respiratory condition. There were 121 females and 204 males. The average age of
      the patients was 40.7 +/- 14.7 years. Only 7% of the patients smoked cigarette.
      The commonest respiratory conditions were tuberculosis (66.8%) and pneumonia
      (24.9%). The commonest comorbidity was HIV infection (39.7%). Tuberculosis/HIV
      coinfection rate was 50.7%. HIV infection was the single most important predictor
      of an adverse outcome (OR 5.1, 95% CI 2.05-12.7, P < 0.001). Conclusion.
      Infective conditions make up a large percentage of respiratory diseases in low
      income countries with HIV infection constituting a significant risk factor for a
      poor disease outcome. 

PMID- 24455245
TI  - Predictive Role of ADA in Bronchoalveolar Lavage Fluid in Making the Diagnosis of
      Pulmonary Tuberculosis.
AB  - Current diagnostic tests for tuberculosis (TB) are time-consuming. The aim of
      this study was to evaluate the diagnostic usefulness of ADA in bronchoalveolar
      lavage fluid in patients with pulmonary TB. A cross-sectional study was performed
      in Yazd, Iran, between 2009 and 2010. Patients suspected of pulmonary TB with
      negative sputum smear for AFB were included in the study. Mean ADA levels in BAL
      fluids were measured and compared between study groups. Sixty-three patients were
      enrolled in the study among which 15 cases had pulmonary TB, 33 had pulmonary
      diseases other than TB, and 15 subjects with normal bronchoscopy results were
      considered as controls. Mean ADA levels in BAL fluid were 4.13 +/- 2.55, 2.42 +/-
      1.06, and 1.93 +/- 0.88, respectively. This rate was significantly higher in the
      pulmonary TB group compared to the other two groups (P = 0.001). Using ROC curve
      with a cut-off value of 3.5 IU/L, the highest sensitivity (57%) and specificity
      (84%) were obtained in diagnosis of TB. The results showed that although ADA
      activity in BAL fluid of pulmonary TB patients was higher than those seen in
      other diseases, a negative test does not rule out pulmonary TB. 

PMID- 24455246
TI  - Computed tomography colonography technique: the role of intracolonic gas volume.
AB  - Introduction. Poor distention decreases the sensitivity and specificity of CTC.
      The total volume of gas administered will vary according to many factors. We aim
      to determine the relationship between the volume of retained gas at the time of
      image acquisition and colonic distention and specifically the presence of
      collapsed bowel segments at CTC. Materials and Methods. All patients who
      underwent CTC over a 12-month period at a single institution were included in the
      study. Colonic luminal distention was objectively scored by 2 radiologists using
      an established 4-point scale. Quantitative analysis of the volume of retained gas
      at the time of image acquisition was conducted using the threshold 3D region
      growing function of OsiriX. Results. 108 patients were included for volumetric
      analysis. Mean retained gas volume was 3.3 L. 35% (38/108) of patients had at
      least one collapsed colonic segment. Significantly lower gas volumes were
      observed in the patients with collapsed colonic segments when compared with those
      with fully distended colons 2.6 L versus 3.5 L (P = 0.031). Retained volumes were
      significantly higher for the 78% of patients with ileocecal reflux at 3.4 L
      versus 2.6 L without ileocecal reflux (P = 0.014). Conclusion. Estimation of
      intraluminal gas volume at CTC is feasible using image segmentation and
      thresholding tools. An average of 3.5 L of retained gas was found in
      diagnostically adequate CTC studies with significantly lower mean gas volume
      observed in patients with collapsed colonic segments. 

PMID- 24455247
TI  - The good life: assessing the relative importance of physical, psychological, and
      self-efficacy statuses on quality of well-being in osteoarthritis patients.
AB  - Background and Purpose. The purpose of the present study was to examine the
      interrelationships among physical dysfunction, self-efficacy, psychological
      distress, exercise, and quality of well-being for people with osteoarthritis. It
      was predicted that exercise would mediate the relationships between physical
      dysfunction, self-efficacy, psychological distress, and quality of well-being.
      Methods. Participants were 363 individuals with osteoarthritis who were 60 years
      of age or older. Data were collected from the baseline assessment period prior to
      participating in a social support and education intervention. A series of
      structural equation models was used to test the predicted relationships among the
      variables. Results. Exercise did not predict quality of well-being and was not
      related to self-efficacy or psychological distress; it was significantly related
      to physical dysfunction. When exercise was removed from the model, quality of
      life was significantly related to self-efficacy, physical dysfunction, and
      psychological distress. Conclusions. Engagement in exercise was directly related
      to physical functioning, but none of the other latent variables. Alternatively,
      treatment focused on self-efficacy and psychological distress might be the most
      effective way to improve quality of well-being. 

PMID- 24455248
TI  - Ethical diversity and the role of conscience in clinical medicine.
AB  - In a climate of plurality about the concept of what is "good," one of the most
      daunting challenges facing contemporary medicine is the provision of medical care
      within the mosaic of ethical diversity. Juxtaposed with escalating scientific
      knowledge and clinical prowess has been the concomitant erosion of unity of
      thought in medical ethics. With innumerable technologies now available in the
      armamentarium of healthcare, combined with escalating realities of financial
      constraints, cultural differences, moral divergence, and ideological divides
      among stakeholders, medical professionals and their patients are increasingly
      faced with ethical quandaries when making medical decisions. Amidst the plurality
      of values, ethical collision arises when the values of individual health
      professionals are dissonant with the expressed requests of patients, the common
      practice amongst colleagues, or the directives from regulatory and political
      authorities. In addition, concern is increasing among some medical practitioners
      due to mounting attempts by certain groups to curtail freedom of independent
      conscience-by preventing medical professionals from doing what to them is
      apparently good, or by compelling practitioners to do what they, in conscience,
      deem to be evil. This paper and the case study presented will explore issues
      related to freedom of conscience and consider practical approaches to ethical
      collision in clinical medicine. 

PMID- 24455249
TI  - Sexual and reproductive health care for women with intellectual disabilities: a
      primary care perspective.
AB  - Adults with intellectual disabilities (ID) face multiple health disparities and
      challenges to accessing health care. Little is known about sexual health care of
      this population and about how to optimize women's reproductive health care for
      women with intellectual disabilities. Women with ID face important barriers to
      care, including lack of provider training and experience, hesitancy to broach the
      topic of sexual health, a lack of sexual knowledge and limited opportunities for
      sex education, disability-related barriers, higher prevalence of sexual abuse and
      assault, often underreported, lack of dialogue around this population's human
      right to consensual sexual expression, undertreatment of menstrual disorders, and
      legal and systemic barriers. We conducted a limited literature review related to
      six aspects of sexual health care of women with ID, including barriers to sexual
      health care, sex education, sexual abuse and consensual sexuality, contraception,
      screening for sexually transmitted infections and cervical cancer, and pregnancy
      and parenting. After providing background information about each topic, we
      suggest practice recommendations for primary care clinicians, using a rights
      based framework. 

PMID- 24455250
TI  - A Pharmacist-Led Point-of-Care INR Clinic: Optimizing Care in a Family Health
      Team Setting.
AB  - Purpose. Monitoring patients' international normalized ratio (INR) within a
      family medicine setting can be challenging. Novel methods of doing this
      effectively and in a timely manner are important for patient care. The purpose of
      this study was to determine the effectiveness of a pharmacist-led point-of-care
      (POC) INR clinic. Methods. At a community-based academic Family Health Team in
      Toronto, Canada, charts of patients with atrial fibrillation managed by a
      pharmacist with usual care (bloodtesting at lab and pharmacist follow up of INR
      by phone) from February 2008 to April 2008 were compared with charts of patients
      attending a weekly POC INR clinic from February 2010 to April 2010. Time in
      therapeutic range (TTR) was measured for both groups. Results. 119 patient charts
      were reviewed and 114 had TTR calculated. After excluding patients with planned
      inconsistent Coumadin use (20), such as initiating Coumadin treatment or stopping
      for a surgical procedure, the mean TTR increased from 64.41% to 77.09% with the
      implementation of the POC clinic. This was a statistically significant difference
      of 12.68% (CI: 1.18, 24.18; P = 0.03). Conclusion. A pharmacist-led POC-INR
      clinic improves control of anticoagulation therapy in patients receiving warfarin
      and should be considered for implementation in other family medicine settings. 

PMID- 24455251
TI  - Everyday living with diabetes described by family members of adult people with
      type 1 diabetes.
AB  - The aim of this study was to explore family members' experiences of everyday life
      in families with adult people living with type 1 diabetes. The grounded theory
      method was used to gather and analyse data from the interviews of nineteen family
      members. Six concepts describing the family members' views on everyday living
      with diabetes were generated on the basis of the data. Everyday life with
      diabetes is described as being intertwined with hypoglycemia. Becoming acquainted
      with diabetes takes place little by little. Being involved in the management and
      watching self-management from the sidelines are concepts describing family
      members' participation in the daily management of diabetes. The family members
      are also integrating diabetes into everyday life. Living on an emotional roller
      coaster tells about the thoughts and feelings that family members experience.
      Family members of adult people with diabetes are involved in the management of
      the diabetes in many ways and experience many concerns. The family members' point
      of view is important to take into consideration when developing education for
      adults with diabetes. 

PMID- 24455252
TI  - Cryoglobulins as potential triggers of inflammation in schizophrenia.
AB  - This case study aimed to investigate effects of type III cryoglobulins isolated
      from the blood of patients with schizophrenia on the production of
      proinflammatory cytokines interleukin(IL)-1 beta , IL-6 and tumor necrosis factor
      alpha (TNF- alpha ), anti-inflammatory cytokine IL-10, and chemotactic cytokines
      IL-8 and monocyte chemoattractant protein-1 (MCP-1) by peripheral blood
      mononuclear cells (PBMCs). The experiments were performed in vitro using PBMCs
      healthy subjects and the blood of patients whit schizoprenia. The enzyme-linked
      immunosorbent assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide assay were used upon study. The results obtained indicated significant
      increase (P < 0.05) in IL-1 beta , IL-6, TNF- alpha , IL-8, and MCP-1 production
      by cultured PBMCs when incubating for 24 hours with cryoglobulins, beginning from
      0.4 mg/mL. The gender difference does not affect the cryoglobulins-induced
      production of these cytokines by PBMCs. No influence of cryoglobulins on
      production of IL-10 by PBMCs was observed. Also, it was shown that cryoglobulins
      in concentration <=4 mg/mL possessed no cytotoxic effect towards cultured PBMCs.
      Based upon the results obtained, we concluded that type III cryoglobulins are
      implicated in schizophrenia-associated alterations in the immune response through
      induction of the expression of proinflammatory and chemotactic cytokines by
      PBMCs. 

PMID- 24455253
TI  - Cognitive remediation in schizophrenia: current status and future perspectives.
AB  - Objectives. This study is aimed to review the current scientific literature on
      cognitive remediation in schizophrenia. In particular, the main structured
      protocols of cognitive remediation developed for schizophrenia are presented and
      the main results reported in recent meta-analyses are summarized. Possible
      benefits of cognitive remediation in the early course of schizophrenia and in
      subjects at risk for psychosis are also discussed. Methods. Electronic search of
      the relevant studies which appeared in the PubMed database until April 2013 has
      been performed and all the meta-analyses and review articles on cognitive
      remediation in schizophrenia have been also taken into account. Results. Numerous
      intervention programs have been designed, applied, and evaluated, with the
      objective of improving cognition and social functioning in schizophrenia. Several
      quantitative reviews have established that cognitive remediation is effective in
      reducing cognitive deficits and in improving functional outcome of the disorder.
      Furthermore, the studies available support the usefulness of cognitive
      remediation when applied in the early course of schizophrenia and even in
      subjects at risk of the disease. Conclusions. Cognitive remediation is a
      promising approach to improve real-world functioning in schizophrenia and should
      be considered a key strategy for early intervention in the psychoses. 

PMID- 24455254
TI  - Factor structure of social cognition in schizophrenia: is empathy preserved?
AB  - Social cognitive impairments are core features of schizophrenia and are closely
      associated with poor functional outcome. This study sought to identify specific
      aspects of social cognition and their relationships to measures of social
      function, quality of life, and neurocognition. Principal component analysis was
      performed using social cognitive measures in patients with schizophrenia and
      healthy matched controls and revealed three factors: Interpersonal Discomfort,
      Basic Social Cognition, and Empathy. Patients had higher scores on Interpersonal
      Discomfort and lower scores on Basic Social Cognition than controls, but the two
      groups were the same on Empathy. Lower social performance was significantly
      correlated with poor Basic Social Cognition in patients and with high
      Interpersonal Discomfort in controls. While neurocognition was significantly
      associated with Basic Social Cognition in both groups, it was not associated with
      Empathy. Social cognitive interventions should emphasize improving basic social
      cognitive processing deficits, managing Interpersonal Discomfort, and utilizing
      preserved capacity for empathy as a potential strength in social interactions. 

PMID- 24455255
TI  - A high-fidelity virtual environment for the study of paranoia.
AB  - Psychotic disorders carry social and economic costs for sufferers and society.
      Recent evidence highlights the risk posed by urban upbringing and social
      deprivation in the genesis of paranoia and psychosis. Evidence based
      psychological interventions are often not offered because of a lack of
      therapists. Virtual reality (VR) environments have been used to treat mental
      health problems. VR may be a way of understanding the aetiological processes in
      psychosis and increasing psychotherapeutic resources for its treatment. We
      developed a high-fidelity virtual reality scenario of an urban street scene to
      test the hypothesis that virtual urban exposure is able to generate paranoia to a
      comparable or greater extent than scenarios using indoor scenes. Participants (n
      = 32) entered the VR scenario for four minutes, after which time their degree of
      paranoid ideation was assessed. We demonstrated that the virtual reality scenario
      was able to elicit paranoia in a nonclinical, healthy group and that an urban
      scene was more likely to lead to higher levels of paranoia than a virtual indoor
      environment. We suggest that this study offers evidence to support the role of
      exposure to factors in the urban environment in the genesis and maintenance of
      psychotic experiences and symptoms. The realistic high-fidelity street scene
      scenario may offer a useful tool for therapists. 

PMID- 24455256
TI  - Microalbuminuria, kidney function, and daily physical activity.
AB  - The present study was carried out to investigate independent relationship between
      daily physical activity, microalbuminuria, and kidney function. The demographic
      characteristics and laboratory parameters were recorded for all patients. The
      determination of daily activities was carried out by Nottingham Extended
      Activities of Daily Living Scale (NEADLS) which was performed for each patient in
      an interview. Totally 139 patients were enrolled. In the whole group NEADLS score
      was correlated with age (rho: -0.759, P < 0.0001), clinical systolic blood
      pressure (rho: -0.212, P: 0.018), blood urea nitrogen (rho: -0.516, P < 0.0001),
      creatinine (rho: -0.501, P < 0.0001), uric acid (rho: -0.308, P < 0.0001),
      albumin (rho: 0.382, P < 0.0001), total cholesterol (rho: -0.194, P: 0.022), LDL
      cholesterol (rho: -0.230, P: 0.008), hemoglobin (rho: 0.256, P: 0.002),
      creatinine clearance (rho: 0.565, P < 0.0001), 24-hour urinary protein excretion
      (rho: -0.324, P < 0.0001), and 24-hour urinary albumin excretion (UAE) (rho: 
      0.483, P < 0.0001). The multivariate linear regression of independent factors
      corelated with logarithmically converted NEADLS score (as a dependent variable)
      has shown that age (P < 0.0001), presence of coronary artery disease (P: 0.011),
      hemoglobin (P: 0.020), 24-hour creatinine clearance (P: 0.004), and 24-hour
      urinary albumin excretion (P < 0.0001) were independently corelated with NEADLS
      score. In conclusion, both UAE and kidney function were independently associated
      with daily physical activity. 

PMID- 24455257
TI  - Investigation of the Association between Genetic Polymorphism of Microsomal
      Epoxide Hydrolase and Primary Brain Tumor Incidence.
AB  - MEH IS A CRITICAL BIOTRANSFORMATION ENZYME THAT CATALYZES THE CONVERSION OF
      XENOBIOTIC EPOXIDE SUBSTRATES INTO MORE POLAR DIOL METABOLITES: it is also
      capable of inactivating a large number of structurally different molecules. Two
      polymorphisms affecting enzyme activity have been described in the exon 3 and 4
      of the mEH gene. The hypothesis of this study is that inherent genetic
      susceptibility to a primary brain tumor is associated with mEH gene
      polymorphisms. The polymorphisms of the mEH gene were determined with PCR-RFLP
      techniques and 255 Turkish individuals. Our results indicate that the frequency
      of the mEH exon 4 polymorphism (in controls) is significantly higher than that of
      primary brain tumor patients (OR = 1.8, 95% CI = 1.0-3.4). This report, however,
      failed to demonstrate a significant association between mEH exon 3 polymorphism
      and primary brain tumor susceptibility in this population. Analysis of patients
      by both histological types of primary brain tumor and gene variants showed no
      association, although analysis of family history of cancer between cases and
      controls showed a statistically significant association (chi (2) = 7.0, P =
      0.01). Our results marginally support the hypothesis that genetic susceptibility
      to brain tumors may be associated with mEPHX gene polymorphisms. 

PMID- 24455258
TI  - Sequence Characterization of Mitochondrial 12S rRNA Gene in Mouse Deer (Moschiola
      indica) for PCR-RFLP Based Species Identification.
AB  - Mitochondrial 12S rRNA has proven to be a useful molecular marker for better
      conservation and management of the endangered species. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) of the mitochondrial 12S rRNA
      gene has proven to be a reliable and efficient tool for the identification of
      different Indian deer species of family cervidae. In the present study,
      mitochondrial 12S rRNA gene sequence of mouse deer (Moschiola indica) belonging
      to the family Tragulidae was characterized and analysed in silico for its use in
      species identification. Genomic DNA was isolated from the hair follicles and
      mitochondrial 12S rRNA gene was amplified using universal primers. PCR product
      was cloned and sequenced for the first time. The sequence of mouse deer showed
      90.04, 90.08, 90.04, 91.2, 90.04, and 90.08% identities with sika deer, sambar,
      hog deer, musk deer, chital, and barking deer, respectively. Restriction mapping
      in Lasergene (DNAstar Inc., Madison, WI, USA) revealed that mouse deer
      mitochondrial 12S rRNA gene sequence can be differentiated from the other deer
      species in PCR-RFLP using RsaI, DdeI, BsrI, and BstSFI. With the help of
      predicted pattern, mouse deer can be identified using genomic DNA from a variety
      of biomaterials, thereby providing molecular aid in wildlife forensics and
      conservation of the species. 

PMID- 24455259
TI  - Older Adults Making End of Life Decisions: An Application of Roy's Adaptation
      Model.
AB  - Purpose. The purpose of this study was to identify variables that influenced
      completion of advanced directives in the context of adaptation from national data
      in older adults. Knowledge gained from this study would help us identify factors
      that might influence end of life discussions and shed light on strategies on
      effective communication on advance care planning. Design and Method. A model
      testing design and path analysis were used to examine secondary data from 938
      participants. Items were extracted from the data set to correspond to variables
      for this study. Scales were constructed and reliabilities were tested. Results.
      The final path model showed that physical impairment, self-rated health,
      continuing to work, and family structure had direct and indirect effects on
      completion of advanced directives. Five percent of the variance was accounted for
      by the path analysis. Conclusion. The variance accounted for by the model was
      small. This could have been due to the use of secondary data and limitations
      imposed for measurement. However, health care providers and families should
      explore patient's perception of self-health as well as their family and work
      situation in order to strategize a motivational discussion on advance directive
      or end of life care planning. 

PMID- 24455260
TI  - Perceived effectiveness of elder abuse interventions in psychological distress
      and the design of culturally adapted interventions: a qualitative study in the
      chinese community in chicago.
AB  - This qualitative study examines US Chinese older adults' views on the perceived
      effectiveness, challenges, and cultural adaptations of elder abuse interventions
      to psychological distress in the Chinese community in Chicago. A community-based
      participatory research approach was implemented to partner with the Chinese
      community. A total of 37 community-dwelling Chinese older adults (age 60+)
      participated in focus group discussions. Data analysis was based on grounded
      theory framework. Our findings suggest that older adults perceived social
      support, empowerment, and community-based interventions design as most effective
      to promote psychological well-being of victims. The perceived preferences were
      similar between elder abuse victims and non-victims. Strategies to culturally
      adapt evidence-based interventions were proposed with respect to nurturing filial
      piety values, familial integrations, and increased independence. Research and
      educational outreach initiatives were also discussed. This study has wide policy
      and practice implications for designing and deploying interventions to reduce
      psychological distress with respect to elder abuse outcome. Cultural relevancy of
      health interventions is important in the context of the Chinese communities.
      Collective federal, state, and community efforts are needed to support the
      culturally appropriate design and implementation of interventions suitable for
      the needs of the Chinese older adults. 

PMID- 24455261
TI  - Jatropha oil derived sophorolipids: production and characterization as laundry
      detergent additive.
AB  - Sophorolipids (SLs) are glycolipidic biosurfactants suitable for various
      biological and physicochemical applications. The nonedible Jatropha oil has been
      checked as the alternative raw material for SL synthesis using C. bombicola
      (ATCC22214). This is useful towards lowering the SL production cost. Through
      optimization of fermentation parameters and use of resting cell method, the yield
      15.25 g/L could be achieved for Jatropha oil derived SL (SLJO) with 1% v/v oil
      feeding. The synthesized SL displayed good surfactant property. It reduced the
      surface tension of distilled water from 70.7 mN/m to 33.5 mN/m with the Critical
      Micelle Concentration (CMC) value of 9.5 mg/L. Keeping the prospective use of the
      SL in mind, the physicochemical properties were checked along with emulsion
      stability under temperature, pH stress, and in hard water. Also antibacterial
      action and stain removal capability in comparison with commercial detergent was
      demonstrated. SLJO enhanced the detergent performance. Based on the results, it
      can be said that SLs have utility as fabric cleaner with advantageous properties
      such as skin friendly nature, antibacterial action, and biodegradability.
      Therefore SLs are potential green molecules to replace synthetic surfactants in
      detergents so as to reduce harm caused to environment through detergent usage. 

PMID- 24455262
TI  - Protective effect of theaflavin on erythrocytes subjected to in vitro oxidative
      stress.
AB  - Antioxidant and free radical scavenging effect of black tea theaflavins has been
      shown in many epidemiological studies. In the present work we report the
      protective mechanism of tea theaflavins on biomarkers of oxidative stress, which
      are elevated during stress conditions. We hereby report the in vitro effect of
      theaflavins on erythrocyte malondialdehyde (MDA), intracellular reduced
      glutathione (GSH), and plasma membrane redox system (PMRS) of rats. The effect of
      theaflavin on PMRS has also been validated through an in silico docking
      simulation study using Molegro Virtual Docker (MVD). We report that theaflavins
      show significant protection to erythrocyte against oxidative stress induced by
      tert-butyl hydroperoxide (t-BHP). The findings suggest a possible protective role
      of theaflavins as antioxidant. 

PMID- 24455263
TI  - Community based assessment of biochemical risk factors for cardiovascular
      diseases in rural and tribal area of himalayan region, India.
AB  - Context. Evident change in nutrition and lifestyle among individuals of urban and
      rural areas raises suspicion for similar change in tribal area population of
      India. Aim. To study the biochemical risk factor for CVDs in rural and tribal
      population of Sub-Himalayan state of India. Settings and Design. Cross-sectional
      study in rural (low altitude) and tribal (high altitude) area of Himachal
      Pradesh, India. Methodology. Blood lipid profile using standard laboratory
      methods. Statistical Analysis. Chi-square test and multiple linear regression
      analysis. Results. Total of 900 individuals were studied in both areas. As per
      Asian criteria, obesity (BMI 27.5-30.0 kg/m(2)) was observed to be significantly
      high (P = 0.00) as 13.7% in tribal area as compared to 5.5% in rural area. Normal
      level of TC (<200 mg/dL) and LDL (<130 mg/dL) was observed in the majority of the
      population of both areas, whereas, at risk level of HDL (<40 mg/dL) was present
      in half of the population of both rural and tribal areas. The prevalence of
      borderline to high level of TGs was observed to be 60.2% and 55.2% in rural and
      tribal (P = 0.10) area, respectively. Conclusion. Prevalent abnormal lipid
      profile in tribal area demands establishment of an effective surveillance system
      for development of chronic diseases. 

PMID- 24455264
TI  - Penetration of milk-derived antimicrobial peptides into phospholipid monolayers
      as model biomembranes.
AB  - Three antimicrobial peptides derived from bovine milk proteins were examined with
      regard to penetration into insoluble monolayers formed with 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC) or 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1
      glycerol) sodium salt (DPPG). Effects on surface pressure (Pi) and electric
      surface potential (DeltaV) were measured, Pi with a platinum Wilhelmy plate and
      DeltaV with a vibrating plate. The penetration measurements were performed under
      stationary diffusion conditions and upon the compression of the monolayers. The
      two type measurements showed greatly different effects of the peptide-lipid
      interactions. Results of the stationary penetration show that the peptide
      interactions with DPPC monolayer are weak, repulsive, and nonspecific while the
      interactions with DPPG monolayer are significant, attractive, and specific. These
      results are in accord with the fact that antimicrobial peptides disrupt bacteria
      membranes (negative) while no significant effect on the host membranes (neutral)
      is observed. No such discrimination was revealed from the compression isotherms.
      The latter indicate that squeezing the penetrant out of the monolayer upon
      compression does not allow for establishing the penetration equilibrium, so the
      monolayer remains supersaturated with the penetrant and shows an under
      equilibrium orientation within the entire compression range, practically. 

PMID- 24455265
TI  - Diffusion Tensor Imaging in NAWM and NADGM in MS and CIS: Association with
      Candidate Biomarkers in Sera.
AB  - The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in
      the corpus callosum and pyramidal tract in normal-appearing white matter (NAWM)
      and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS
      subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined
      whether these metrics are associated with clinical measures and the serum levels
      of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were
      significantly higher than in controls in all six studied NAWM regions in SPMS,
      4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased
      fractional anisotropy (FA) values in comparison to controls were detected in 2/6
      NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological
      disability correlated with thalamic FA values (r = 0.479, P = 0.004). In chronic
      progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with
      the levels of MIF, sFas, and sTNF- alpha . Our data indicate that DTI may be
      useful in detecting pathological changes in NAWM and NADGM in MS patients and
      that these changes are related to neurological disability. 

PMID- 24455266
TI  - Multiple sclerosis in malaysia: demographics, clinical features, and neuroimaging
      characteristics.
AB  - Background. Multiple sclerosis (MS) is an uncommon disease in multiracial
      Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases
      has been greatly aided by the evolution in diagnostic criterion, the
      identification of new biomarkers, and improved accessibility to neuroimaging in
      the country. Objectives. To investigate the spectrum of multiple sclerosis in
      Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients
      referred to a single tertiary medical center with neurology services in Malaysia.
      Results. Out of 245 patients with idiopathic inflammatory demyelinating disease,
      104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at
      onset was 28.6 +/- 9.9 years. The Malays were the predominant racial group
      affected followed by the Chinese, Indians, and other indigenous groups. Subgroup
      analysis revealed more Chinese having neuromyelitis optica and its spectrum
      disorders rather than multiple sclerosis. Positive family history was reported in
      5%. Optic neuritis and myelitis were the commonest presentations at onset of
      disease, and relapsing remitting course was the commonest disease pattern
      observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and
      66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space.
      Mean cord lesion length was 1.86 +/- 1.65 vertebral segments in the relapsing
      remitting group as opposed to 6.25 +/- 5.18 vertebral segments in patients with
      neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of
      multiple sclerosis in Malaysia has changed over the years. Further advancement in
      diagnostic criteria will no doubt continue to contribute to the evolution of this
      disease here. 

PMID- 24455267
TI  - Future of management of multiple sclerosis in the middle East: a consensus view
      from specialists in ten countries.
AB  - The prevalence of multiple sclerosis (MS) is now considered to be medium-to-high
      in the Middle East and is rising, particularly among women. While the
      characteristics of the disease and the response of patients to disease-modifying
      therapies are generally comparable between the Middle East and other areas,
      significant barriers to achieving optimal care for MS exist in these developing
      nations. A group of physicians involved in the management of MS in ten Middle
      Eastern countries met to consider the future of MS care in the region, using a
      structured process to reach a consensus. Six key priorities were identified:
      early diagnosis and management of MS, the provision of multidisciplinary MS
      centres, patient engagement and better communication with stakeholders,
      regulatory body education and reimbursement, a commitment to research, and more
      therapy options with better benefit-to-risk ratios. The experts distilled these
      priorities into a single vision statement: "Optimization of patient-centred
      multidisciplinary strategies to improve the quality of life of people with MS."
      These core principles will contribute to the development of a broader consensus
      on the future of care for MS in the Middle East. 

PMID- 24455269
TI  - The superior transverse scapular ligament in fetuses.
AB  - Introduction. The superior transverse scapular ligament (STSL) links the margins
      of the suprascapular notch and converts it into a foramen, through which, the
      suprascapular nerve and, on some rare occasions, the suprascapular vessels pass.
      This conversion often results from partial or complete ossification of the STSL
      and may produce compressive symptoms in the suprascapular nerve. Material and
      Method. Twenty shoulders from human fetuses were dissected without the aid of
      optical instruments and, using a digital pachymeter of precision 0.01
      millimeters, length measurements and thickness measurements were made. The fetal
      age was from 21 to 33 weeks of gestation, with a mean of 27.6 +/- 4.14 weeks.
      Results. There was no statistically significant difference in STSL length or any
      difference in the thicknesses at the medial and lateral extremities between the
      halves of the body (P >= 0.05). However, in the left half of the body, the medial
      extremity of the STSL was significantly thinner than the lateral extremity (P <=
      0.05). Conclusion. Anatomical and morphometric details about the STSL were
      described in human fetuses. These findings, in fetuses, may encourage the pursuit
      of further studies to understand the morphofunctional role and meaning of this
      small ligament. 

PMID- 24455268
TI  - Root anatomy and root canal configuration of human permanent mandibular
      premolars: a systematic review.
AB  - Introduction. Mandibular premolars have been reported with complex anatomical
      aberrations, making them one of the most difficult teeth to manage
      endodontically. Methodology. An exhaustive search was undertaken to identify
      associated anatomic studies of mandibular premolars through MEDLINE/PubMed
      database using keywords, and a systematic review of the relevant articles was
      performed. Chi-square test with Yates correction was performed to assess the
      statistical significance of any anatomic variations between ethnicities and
      within populations of the same ethnicity. Documented case reports of variations
      in mandibular premolar anatomy were also identified and reviewed. Results. Thirty
      six anatomic studies were analyzed which included 12,752 first premolars and
      nineteen studies assessing 6646 second premolars. A significant variation in the
      number of roots, root canals, and apical foramen was observed between Caucasian,
      Indian, Mongoloid, and Middle Eastern ethnicities.The most common anatomic
      variation was C-shaped canals in mandibular first premolars with highest
      incidence in Mongoloid populations (upto 24%) while dens invaginatus was the most
      common developmental anomaly. Conclusions. A systematic review of mandibular
      premolars based on ethnicity and geographic clusters offered enhanced analysis of
      the prevalence of number of roots and canals, their canal configuration, and
      other related anatomy. 

PMID- 24455271
TI  - Thrombophilic Genetic Factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin
      20210A in Noncirrhotic Portal Vein Thrombosis and Budd-Chiari Syndrome in a
      Caucasian Population.
AB  - Thrombophilic genetic factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin
      20210A were studied as risk factors in 235 Caucasian subjects: 85 patients with
      abdominal thrombosis (54 with portal vein thrombosis (PVT) and 31 with Budd
      Chiari syndrome (BCS) without liver cirrhosis or hepatocellular carcinoma) and
      150 blood bank donors. Seventy-five patients with PVT/BCS showed associated
      disease or particular clinical status (46 PVT/29 BCS): 37 myeloproliferative
      neoplasm (20 PVT/17 BCS), 12 abdominal surgery (10 PVT/2 BCS), 10 contraception
      or pregnancy (6 PVT/4 BCS), 7 abdominal acute disease (6 PVT/1 BCS), and 9
      chronic disease (4 PVT/5 BCS); ten patients did not present any association (8
      PVT/2 BCS). PAI-14G-4G, MTHFR677TT, and V Leiden 506Q were significantly frequent
      (OR 95% CI and chi (2) test with P value) in abdominal thrombosis; in these
      patients PAI-14G-4G and MTHFR677TT distributions deviated from that expected from
      a population in the Hardy-Weinberg equilibrium (PAI-1: chi (2) = 13.8, P < 0.001;
      MTHFR677: chi (2) = 7.1, P < 0.01), whereas the equilibrium was respected in
      healthy controls. V Leiden Q506 and Prothrombin 20210A were in the Hardy-Weinberg
      equilibrium both in patients with abdominal thrombosis and healthy controls. Our
      study shows an important role of PAI-14G-4G and MTHFR677TT in abdominal
      thrombosis without liver cirrhosis or hepatocellular carcinoma. 

PMID- 24455270
TI  - Transcranial Doppler ultrasound: a review of the physical principles and major
      applications in critical care.
AB  - Transcranial Doppler (TCD) is a noninvasive ultrasound (US) study used to measure
      cerebral blood flow velocity (CBF-V) in the major intracranial arteries. It
      involves use of low-frequency (<=2 MHz) US waves to insonate the basal cerebral
      arteries through relatively thin bone windows. TCD allows dynamic monitoring of
      CBF-V and vessel pulsatility, with a high temporal resolution. It is relatively
      inexpensive, repeatable, and portable. However, the performance of TCD is highly
      operator dependent and can be difficult, with approximately 10-20% of patients
      having inadequate transtemporal acoustic windows. Current applications of TCD
      include vasospasm in sickle cell disease, subarachnoid haemorrhage (SAH), and
      intra- and extracranial arterial stenosis and occlusion. TCD is also used in
      brain stem death, head injury, raised intracranial pressure (ICP), intraoperative
      monitoring, cerebral microembolism, and autoregulatory testing. 

PMID- 24455273
TI  - Imaging and image transfer in emergency medicine.

PMID- 24455272
TI  - Does the integration of personalized ultrasound change patient management in
      critical care medicine? Observational trials.
AB  - Objective. To test the influence of personalized ultrasound (PersUS) on patient
      management in critical care. Design of the Study. Prospective, observational, and
      critical care setting. Four substudies compared PersUS and mobile ultrasound,
      work distribution, and diagnostic and procedural quality. Patients and
      Interventions. 640 patient ultrasound exams including 548 focused diagnostic
      exams and 92 interventional procedures. Main Outcome Measures. Number of studies,
      physician's judgement of feasibility, time of usage per patient, and referrals to
      echo lab. Results. Randomized availability of PersUS increased its application in
      ICU work shifts more than twofold from 33 to 68 exams mainly for detection and
      therapy of effusions. Diagnostic and procedural quality was rated as
      excellent/very good in PersUS-guided puncture in 95% of cases. Integrating PersUS
      within an initial physical examination of 48 randomized cases in an emergency
      department, PersUS extended the examination time by 100 seconds. Interestingly,
      PersUS integration into 53 randomized regular ward rounds of 1007 patients
      significantly reduced average contact time per patient by 103 seconds from 8.9 to
      7.2 minutes. Moreover, it lowered the patient referral rate to an echo lab from
      20% to 2% within the study population. Conclusions. We propose the development of
      novel ultrasound-based clinical pathways by integration of PersUS. 

PMID- 24455274
TI  - Shoulder pain, functional status, and health-related quality of life after head
      and neck cancer surgery.
AB  - Head and neck cancer (HNC) patients experience treatment-related complications
      that may interfere with health-related quality of life (HRQOL). The purpose of
      this study was to describe the symptom experience (shoulder pain) and functional
      status factors that are related to global and domain-specific HRQOL at one month
      after HNC surgery. In this exploratory study, we examined 29 patients. The
      outcome variables included global HRQOL as well as physical, functional,
      emotional, and social well-being. Symptom experience and functional status
      factors were the independent variables. In the symptom experience variables,
      shoulder pain distress was negatively associated with physical well-being (R (2)
      = 0.24). Among the functional status variables, eating impairment was negatively
      related to global HRQOL (R (2) = 0.18) and physical well-being (R (2) = 0.21).
      Speaking impairment and impaired body image explained a large amount of the
      variance in functional well-being (R (2) = 0.45). This study provided initial
      results regarding symptom experience and functional status factors related to
      poor HRQOL in the early postoperative period for HNC patients. 

PMID- 24455275
TI  - Home-Based Multidisciplinary Rehabilitation following Hip Fracture Surgery: What
      Is the Evidence?
AB  - Objective. To determine the effects of multidisciplinary home rehabilitation
      (MHR) on functional and quality of life (QOL) outcomes following hip fracture
      surgery. Methods. Systematic review methodology suggested by Cochrane
      Collboration was adopted. Reviewers independently searched the literature,
      selected the studies, extracted data, and performed critical appraisal of
      studies. Summary of the results of included studies was provided. Results. Five
      studies were included. Over the short-term, functional status and lower extremity
      strength were better in the MHR group compared to the no treatment group (NT).
      Over the long-term, the MHR group showed greater improvements in balance
      confidence, functional status, and lower extremity muscle strength compared to NT
      group, whereas the effect on QOL and mobility was inconsistent across the
      studies. Several methodological issues related to study design were noted across
      the studies. Conclusion. The MHR was found to be more effective compared to the
      NT in improving functional status and lower extremity strength in patients with
      hip fracture surgery. Results of this review do not make a strong case for MHR
      due to high risk of bias in the included studies. Further research is required to
      accurately characterize the types of disciplines involved in MHR and frequency
      and dosage of intervention. 

PMID- 24455276
TI  - Prediction of sentinel node status and clinical outcome in a melanoma centre.
AB  - Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for
      patients with localized cutaneous melanoma. The National Comprehensive Cancer
      Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph
      node (SLN) as an important prognostic factor for melanoma survival. We sought to
      identify predictive factors associated with a positive SLNB and overall survival
      in our population. Methods. We performed a retrospective chart review of 221
      patients who have done a successful SLNB for melanoma between 2004 and 2010 at
      our department. Univariate and multivariate analyses were done. Results. The SLNB
      was positive in 48 patients (21.7%). Univariate analysis showed that male gender,
      increasing Breslow thickness, tumor type, and absence of tumor-infiltrating
      lymphocytes were significantly associated with a positive SLNB. Multivariate
      analysis confirmed that Breslow thickness and the absence of tumor-infiltrating
      lymphocytes are independently predictive of SLN metastasis. The 5-year survival
      rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients.
      Breslow thickness and the SLN status independently predict overall survival.
      Conclusions. The risk factors for a positive SLNB are consistent with those found
      in the previous literature. In addition, the SLN status is a major determinant of
      survival, which highlights its importance in melanoma management. 

PMID- 24455277
TI  - Analgesic, anti-inflammatory and anticancer activities of extra virgin olive oil.
AB  - Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy
      for a variety of diseases. This study investigates the in vivo antinociceptive,
      anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials
      and Methods. In this experimental study, using the acetic acid-induced writhing
      and formalin tests in mice, the analgesic effect of EVOO was evaluated.
      Acetylsalicylic acid and morphine were used as standard drugs, respectively. The
      anti-inflammatory activity was investigated by means of the carrageenan-induced
      paw edema model in rats using acetylsalicylic acid and dexamethasone as standard
      drugs. Last, the xenograft model in athymic mice was used to evaluate the
      anticancer effect in vivo. Results. EVOO significantly decreased acetic acid
      induced abdominal writhes and reduces acute and inflammatory pain in the two
      phases of the formalin test. It has also a better effect than Dexamethasone in
      the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO
      affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion.
      EVOO has a significant analgesic, anti-inflammatory, and anticancer properties.
      However, further detailed studies are required to determine the active component
      responsible for these effects and mechanism pathway. 

PMID- 24455279
TI  - Pathogenicity, Ovicidal Action, and Median Lethal Concentrations (LC 50 ) of
      Entomopathogenic Fungi against Exotic Spiralling Whitefly, Aleurodicus dispersus
      Russell.
AB  - Biological control using entomopathogenic fungi could be a promising alternative
      to chemical control. Entomopathogenic fungi, Beauveria bassiana (Balsamo)
      Vuillemin, Metarhizium anisopliae (Metschnikoff) Sorokin, Lecanicillium lecanii
      (Zimmerm.) Zare and Gams, and Paecilomyces fumosoroseus (Wize) Brown and Smith,
      were tested for their pathogenicity, ovicidal effect, and median lethal
      concentrations (LC50) against exotic spiralling whitefly, Aleurodicus dispersus
      Russell. The applications were made at the rate of 2 * 10(9) conidia mL(-1) for
      evaluating the pathogenicity and ovicidal effect of entomopathogenic fungi
      against A. dispersus. The results of pathogenicity test showed that P.
      fumosoroseus (P1 strain) was highly pathogenic to A. dispersus recording 100%
      mortality at 15 days after treatment (DAT). M. anisopliae (M2 strain) had more
      ovicidal effect causing 37.3% egg mortality at 8 DAT. However, L. lecanii (L1
      strain) caused minimum egg hatchability (23.2%) at 10 DAT as compared to control
      (92.6%). The lowest LC50 produced by P. fumosoroseus (P1 strain) as 8.189 * 10(7)
      conidia mL(-1) indicated higher virulence against A. dispersus. Hence, there is
      potential for use of entomopathogenic fungi in the field conditions as an
      alternate control method in combating the insect pests and other arthropod pests
      since they are considered natural mortality agents and are environmentally safe. 

PMID- 24455278
TI  - Deficiency of 25-hydroxyvitamin d and dyslipidemia in Indian subjects.
AB  - Background. Vitamin D deficiency is widespread throughout the world. Several
      reports have incriminated vitamin D deficiency as the cause of rickets,
      osteomalacia, and other chronic diseases. Recent studies have suggested a
      possible link between deficiency of 25-hydroxyvitamin D and dyslipidemia. Aim. To
      investigate the association between 25-hydroxyvitamin D deficiency and
      dyslipidemia in Indian subjects. Methodology. We recruited 150 asymptomatic
      consecutive subjects from patients' attendees at the Departments of Neurology and
      Medicine in Yashoda Hospital, Hyderabad, India. Study period was from October
      2011 to March 2012. All subjects underwent 25-hydroxyvitamin D assay by
      chemiluminescent microparticle immunoassay, fasting blood sugar and lipid
      profile, calcium, phosphorus, alkaline phosphatase, and C-reactive protein (CRP).
      Results. Out of 150 subjects, men were 82 (54.6%), and mean age was 49.4 (+/
      15.6) years. Among risk factors, hypertension was noted in 63/150 (42%), 25
      hydroxyvitamin D deficiency in 59/150 (39.3%), diabetes in 45/150 (30%),
      dyslipidemia in 60 (40%), smoking in 35/150 (23.3%), and alcoholism in 27/150
      (18%). Deficiency of 25-hydroxyvitamin D was significantly associated with
      dyslipidemia (P = 0.0001), mean serum glucose (P = 0.0002) mean CRP (P = 0.04),
      and mean alkaline phosphatase (P = 0.01). Multivariate analysis showed that 25
      hydroxyvitamin D deficiency was independently associated with dyslipidemia (odds
      ratio: 1.9; 95% CI : 1.1-3.5). Conclusions. We found that deficiency of 25
      hydroxyvitamin D was independently associated with dyslipidemia in Indian
      subjects. 

PMID- 24455280
TI  - Antibiotic Resistance of Salmonella spp. Isolated from Shrimp Farming Freshwater
      Environment in Northeast Region of Brazil.
AB  - This study investigated the presence and antibiotic resistance of Salmonella spp.
      in a shrimp farming environment in Northeast Region of Brazil. Samples of water
      and sediments from two farms rearing freshwater-acclimated Litopenaeus vannamei
      were examined for the presence of Salmonella. Afterwards, Salmonella isolates
      were serotyped, the antimicrobial resistance was determined by a disk diffusion
      method, and the plasmid curing was performed for resistant isolates. A total of
      30 (16.12%) of the 186 isolates were confirmed to be Salmonella spp., belonging
      to five serovars: S. serovar Saintpaul, S. serovar Infantis, S. serovar Panama,
      S. serovar Madelia, and S. serovar Braenderup, along with 2 subspecies: S.
      enterica serovar houtenae and S. enterica serovar enterica. About twenty-three
      percent of the isolates were resistant to at least one antibiotic, and twenty
      percent were resistant to at least two antibiotics. Three strains isolated from
      water samples (pond and inlet canal) exhibited multiresistance to ampicillin,
      tetracycline, oxytetracycline, and nitrofurantoin. One of them had a plasmid with
      genes conferring resistance to nitrofurantoin and ampicillin. The incidence of
      bacteria pathogenic to humans in a shrimp farming environment, as well as their
      drug-resistance pattern revealed in this study, emphasizes the need for a more
      rigorous attention to this area. 

PMID- 24455281
TI  - DNA methylation pattern as important epigenetic criterion in cancer.
AB  - Epigenetic modifications can affect the long-term gene expression without any
      change in nucleotide sequence of the DNA. Epigenetic processes intervene in the
      cell differentiation, chromatin structure, and activity of genes since the
      embryonic period. However, disorders in genes' epigenetic pattern can affect the
      mechanisms such as cell division, apoptosis, and response to the environmental
      stimuli which may lead to the incidence of different diseases and cancers. Since
      epigenetic changes may return to their natural state, they could be used as
      important targets in the treatment of cancer and similar malignancies. The aim of
      this review is to assess the epigenetic changes in normal and cancerous cells,
      the causative factors, and epigenetic therapies and treatments. 

PMID- 24455282
TI  - Feasibility of whole RNA sequencing from single-cell mRNA amplification.
AB  - Single-cell sampling with RNA-seq analysis plays an important role in reference
      laboratory; cytogenomic diagnosis for specimens on glass-slides or rare cells in
      circulating blood for tumor and genetic diseases; measurement of sensitivity and
      specificity in tumor-tissue genomic analysis with mixed-cells; mechanism analysis
      of differentiation and proliferation of cancer stem cell for academic purpose.
      Our single- cell RNA-seq technique shows that fragments were 250-450 bp after
      fragmentation, amplification, and adapter addition. There were 11.6 million reads
      mapped in raw sequencing reads (19.6 million). The numbers of mapped genes,
      mapped transcripts, and mapped exons were 31,332, 41,210, and 85,786,
      respectively. All QC results demonstrated that RNA-seq techniques could be used
      for single-cell genomic performance. Analysis of the mapped genes showed that the
      number of genes mapped by RNA-seq (6767 genes) was much higher than that of
      differential display (288 libraries) among similar specimens which we have
      developed and published. The single-cell RNA-seq can detect gene splicing using
      different subtype TGF-beta analysis. The results from using Q-rtPCR tests
      demonstrated that sensitivity is 76% and specificity is 55% from single-cell RNA
      seq technique with some gene expression missing (2/8 genes). However, it will be
      feasible to use RNA-seq techniques to contribute to genomic medicine at single
      cell level. 

PMID- 24455283
TI  - Utilization of Oncotype DX in an Inner City Population: Race or Place?
AB  - Oncotype DX, a 21-gene-array analysis, can guide chemotherapy treatment decisions
      for women with ER+ tumors. Of 225 ER+ women participating in a patient assistance
      trial, 23% underwent Oncotype DX testing: 31% of whites, 21% of blacks, and 14%
      of Hispanics (P = 0.04) were tested. Only 3 white women were treated at municipal
      hospitals and none was tested. 3% of women treated in municipal hospital as
      compared to 30% treated at tertiary referral centers were tested (P = 0.001).
      Within tertiary referral centers, there was no racial difference in testing: 32%
      of whites, 29% of blacks, and 19% of Hispanics (P = 0.25). Multivariate analysis
      (model c-statistic = 0.76; P < 0.0001) revealed that women who underwent testing
      were more likely to have stage 1B (RR = 1.70; 95% CI: 1.45-1.85) and to be
      treated after 2007 (RR = 1.34; 95% CI: 1.01-1.65) and less likely to be treated
      at a municipal hospital (RR = 0.20; 95% CI: 0.04-0.94). Women treated at
      municipal hospitals were less likely to undergo testing resulting in a misleading
      racial disparity that is driven by site of care. As Oncotype DX can reduce
      overuse of chemotherapy, it is imperative to expand testing to those who could
      benefit from yet experience underuse of this test, namely, women treated at
      safety net hospitals. This trial is registered with NCT00233077. 

PMID- 24455284
TI  - Accuracy of individual descriptors and grading of nodal involvement by axillary
      ultrasound in patients of breast cancer.
AB  - Background. Four-node sampling is a useful substitute for sentinel node biopsy in
      low resource settings. USG is being increasingly used as a preoperative tool to
      evaluate axilla. We conducted this study to assess the accuracy of different
      descriptors of axillary ultrasound and to formulate a model on grading of
      axillary involvement. Material and Methods. Thirty-four patients with clinically
      negative axilla underwent preoperative axillary ultrasound. The suspicious nodes
      were marked and details of various descriptors were noted. These nodes were
      sampled during axillary dissection and correlation of ultrasonographic findings
      with histopathological report was done to calculate accuracy of different
      descriptors. Based on this, a grading system of axillary lymph nodes involvement
      was formulated. Results. Based on the presence of various descriptors, five
      grades of nodal involvement could be defined. The most accurate descriptors to
      indicate nodal involvement were loss of hilar fat and hypoechoic internal echoes
      with specificity of 83% and positive predictive value of 92% each. The
      combination of descriptors of round shape with loss of hilar fat and hypoechoic
      internal echos had 100% specificity and positive predictive value. Conclusions.
      Grading of nodal involvement on axillary USG can be useful for selecting the most
      suspicious nodes for sampling during axillary dissection. 

PMID- 24455285
TI  - The role of bridging therapy in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver
      accounting for 7% of all cancers worldwide. Most cases of HCC develop within an
      established background of chronic liver disease. For that reason, liver resection
      is only possible in selected patients. Liver transplantation has become the
      treatment of choice in patients with HCC, end-stage liver disease, and
      significant portal hypertension. Shortage of organ donors has resulted in overall
      increase of waiting list time with increased risk of dropout due to tumor
      progression. Neoadjuvant therapies have emerged as an alternative to control
      tumor growth in patients while waiting. The aim of this study is to review the
      literature on the role of bridging therapy and downstaging prior to liver
      transplantation in patients with HCC. We are also presenting our single-center
      experience of 96 patients undergoing transplantation for HCC with and without
      bridging therapy. 

PMID- 24455287
TI  - Current concepts in robotics for the treatment of joint disease.

PMID- 24455286
TI  - Quantification of pregenomic RNA and covalently closed circular DNA in hepatitis
      B virus-related hepatocellular carcinoma.
AB  - Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA)
      and plays important roles in viral genome amplification and replication. Hepatic
      pgRNA and cccDNA expression levels indicate viral persistence and replication
      activity. This study was aimed to measure hepatic pgRNA and cccDNA expression
      levels in various states of hepatitis B virus (HBV) infection. Thirty-eight
      hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B
      surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis
      B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but
      anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous
      liver tissues for at least two genomic regions based on polymerase chain reaction
      (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected
      patients were significantly lower than those in HBsAg-positive patients (P <
      0.001). pgRNA and cccDNA in cancerous tissues were also detected without
      significant difference from those in noncancerous tissues. In conclusion, cccDNA
      and pgRNA are detected and represented HBV replication not only in noncancerous
      but also in cancerous liver tissues. In addition, the replication is shown in not
      only patients with HBsAg-positive but also occult HBV-infected patients,
      suggesting the contribution to HCC development. 

PMID- 24455288
TI  - What does it cost to prevent on-duty firefighter cardiac events? A content valid
      method for calculating costs.
AB  - Cardiac arrest is a leading cause of mortality among firefighters. We sought to
      develop a valid method for determining the costs of a workplace prevention
      program for firefighters. In 2012, we developed a draft framework using human
      resource accounting and in-depth interviews with experts in the firefighting and
      insurance industries. The interviews produced a draft cost model with 6
      components and 26 subcomponents. In 2013, we randomly sampled 100 fire chiefs out
      of >7,400 affiliated with the International Association of Fire Chiefs. We used
      the Content Validity Index (CVI) to identify the content valid components of the
      draft cost model. This was accomplished by having fire chiefs rate the relevancy
      of cost components using a 4-point Likert scale (highly relevant to not
      relevant). We received complete survey data from 65 fire chiefs (65% response
      rate). We retained 5 components and 21 subcomponents based on CVI scores >=0.70.
      The five main components include, (1) investment costs, (2) orientation and
      training costs, (3) medical and pharmaceutical costs, (4) education and
      continuing education costs, and (5) maintenance costs. Data from a diverse sample
      of fire chiefs has produced a content valid method for calculating the cost of a
      prevention program among firefighters. 

PMID- 24455289
TI  - Fundal height growth curve for underweight and overweight and obese pregnant
      women in Thai population.
AB  - Objectives. To develop fundal height growth curves for underweight and overweight
      and obese pregnant women based on gestational age from last menstrual period
      and/or ultrasound. Methods. A retrospective study was conducted at four hospitals
      in the northern part of Thailand between January 2009 and March 2011. Fundal
      height, gestational age, height, and prepregnancy weight were extracted from
      antenatal care and delivery records. Fundal height growth curves were presented
      as smoothed function of the 10th, 50th, and 90th percentiles between 20 and 40
      weeks of gestation, derived from multilevel models. Results. Fundal height growth
      curve of the underweight was derived from 1,486 measurements (208 women) and the
      overweight and obese curve was derived from 1,281 measurements (169 women). The
      50th percentile line of the underweight was 0.1-0.4 cm below the normal weight at
      weeks 23-31 and 0.5-0.8 cm at weeks 32-40. The overweight and obese line was 0.1
      0.4 cm above the normal weight at weeks 22-29 and 0.6-0.8 cm at weeks 30-40.
      Conclusions. Fundal height growth curves of the underweight and overweight and
      obese pregnant women were different from the normal weight. In monitoring or
      screening for abnormal intrauterine growth in these women, fundal height growth
      curves specifically developed for such women should be applied. 

PMID- 24455290
TI  - A new surgical method of suprapubic and extraperitoneal approach with uterine
      preservation for pelvic organ prolapse: kurt extraperitoneal ligamentopexy.
AB  - Objective. To introduce an alternative surgical approach for the optimal
      treatment of pelvic organ prolapse (POP). Methods. Twenty symptomatic women with
      grades 2-4 POP diagnosis who opted to choose this alternative surgery were
      retrospectively analyzed. Results. A total of 22 cases were included. The mean
      age of the patients was 50.6 +/- 13.2 years (29-72 years) with a mean gravid and
      parity of 5.5 +/- 2.66 and 3.4 +/- 2.06, respectively. The mean body-mass index
      of the patients was 24.25 +/- 2.43. Nine (45%) patients were premenopausal and 11
      (55%) patients were postmenopausal. Uterine descensus was present in all
      patients, and additionally cystorectocele in 9 patients (45%), cystocele in 6
      patients (30%), rectocele in 4 patients (20%), and elangatio colli in 6 patients
      (30%) were diagnosed. In addition to the alternative surgery, Manchester
      procedure and anteroposterior vaginal wall repair or Burch procedure was
      performed where necessary. Mean follow-up time was 48.95 +/- 42.8 months (6-171
      months). No recurrence of POP occurred. Conclusions. Suprapubic, extraperitoneal,
      and minimally invasive ligamentopexy of the round ligament to the anterior rectus
      fascia offers an alternative to conventional POP surgery with favorable outcomes
      without any recurrence. 

PMID- 24455291
TI  - Detection of Antibodies and Confirmation of Mycobacterium avium Subspecies
      paratuberculosis Using Nested PCR in Bulk Milk Samples from Nakasongola and
      Sembabule Districts, Uganda.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) is an emerging pathogen in
      many livestock and wildlife populations around the world. Concerns range from the
      serious economic impacts on livestock productivity to its suspected role in the
      human inflammatory bowel disease syndrome. Milk and faeces of infected animals
      are the main vehicles through which the organism spreads from infected to
      susceptible hosts. In this study, a survey was done in Nakasongola and Sembabule
      districts of Uganda involving a total of seven dairy collection centres to
      determine the prevalence of antibodies to MAP in bulk milk samples. The milk was
      tested with a commercial ELISA kit for MAP testing in milk. Positive and
      suspicious milk samples were further tested using nested PCR. Of the 257 milk
      samples tested, 11 (4.3%) were positive and five (1.9%) were suspicious. All the
      ELISA positive and suspicious milk samples were positive using nested PCR. The
      results show that MAP infection occurs in cattle from the two districts and
      highlight the need for a paratuberculosis control program in these and other
      districts where MAP infection has been reported. 

PMID- 24455292
TI  - Investigation of the Distribution of Salmonella within an Integrated Pig Breeding
      and Production Organisation in the United Kingdom.
AB  - To examine patterns of Salmonella herd infections in units linked by common
      sources of pigs, the study examined pooled pen faeces samples from 161 nursery
      and finishing units in a UK integrated pig enterprise. An epidemiological
      questionnaire was also completed by investigators for each farm. Salmonella was
      isolated from 630 (19.5%) of the samples: S. Typhimurium was found in 387 (12%)
      and S. Derby in 157 (4.9%) samples; 111 units yielded at least one sample
      containing Salmonella. The proportion of Salmonella-positive samples from
      positive farms ranged from 5% to 95%. In a univariable risk factor analysis,
      increasing length of time as a pig farm was positively associated with the
      detection of Salmonella in a herd. Larger farms (>500 pigs) were significantly
      more likely to be positive for S. Typhimurium than smaller farms. There was an
      association between Salmonella serovars isolated in the present study and those
      subsequently isolated in breeding herds linked to the integration. 

PMID- 24455293
TI  - Vitamin d supplementation for the treatment of acute childhood pneumonia: a
      systematic review.
AB  - Background. Studies have found an increased incidence of vitamin D deficiency in
      children with pneumonia; however, there is no conclusive data regarding the
      direct effect of vitamin D supplementation in acute pneumonia. Methods. A
      comprehensive search was performed of the major electronic databases till
      September 2013. Randomized controlled trials (RCTs) comparing treatment with
      vitamin D3 versus placebo in children <=5 years old with pneumonia were included.
      Results. Out of 32 full text articles, 2 RCTs including 653 children were
      eligible for inclusion. One trial used a single 100,000 unit of oral vitamin D3
      at the onset of pneumonia. There was no significant difference in the mean (+/
      SD) number of days to recovery between the vitamin D3 and placebo arms (P =
      0.17). Another trial used oral vitamin D3 (1000 IU for <1 year and 2000 IU for >1
      year) for 5 days in children with severe pneumonia. Median duration of resolution
      of severe pneumonia was similar in the two groups (intervention, 72 hours;
      placebo, 64 hours). Duration of hospitalization and time to resolution of
      tachypnea, chest retractions, and inability to feed were also comparable between
      the two groups. Conclusions. Oral vitamin D supplementation does not help
      children under-five with acute pneumonia. 

PMID- 24455294
TI  - Role of electrical impedance tomography in clinical practice in pediatric
      respiratory medicine.
AB  - This paper summarizes current knowledge about electrical impedance tomography
      (EIT) and its present and possible applications in clinical practice in pediatric
      respiratory medicine. EIT is a relatively new technique based on real-time
      monitoring of bioimpedance. Its possible application in clinical practice related
      to ventilation and perfusion monitoring in children has gaine increasing
      attention in recent years. Most of the currently published data is based on
      studies performed on small and heterogenous groups of patients. Thus the results
      need to be corroborated in future well-designed clinical trials. Firstly a short
      theoretical overview summarizing physical principles and main advantages and
      disadvantages is provided. It is followed by a review of the current data
      regarding EIT application in ventilation distribution monitoring in healthy
      individuals. Finally the most important studies utilizing EIT in ventilation and
      perfusion monitoring in critically ill newborns and children are outlined. 

PMID- 24455295
TI  - Silica-ZnCl 2 : An Efficient Catalyst for the Synthesis of 4-Methylcoumarins.
AB  - Silica-ZnCl2 has been found to be an efficient and eco-friendly catalyst for the
      synthesis of substituted 4-methylcoumarins from ethyl acetoacetate and
      substituted phenols under "neat" conditions in an oil bath at 80 degrees C. The
      experimental procedure is simple, includes shorter reaction times (15-65 min),
      compatible with sensitive functional groups, and results in excellent yield of
      the products. 

PMID- 24455296
TI  - Goniomitine: an overview on the chemistry of this indole alkaloid.
AB  - This paper reports an overview on the chemistry of the indole alkaloid
      goniomitine focusing, mainly, on the methods of synthesis related to this natural
      product and analogs. 

PMID- 24455297
TI  - An Efficient Synthesis of Bis-indolylindane-1,3-diones, Indan-1,3-diones, and
      Indene-1,3(2H)-denies Using [Hbim]BF 4 Ionic Medium.
AB  - We prepared a brand new molecule in one step for the synthesis of bis
      indolylindane-1,3-dione and indan-1,3-diones from the reaction of ninhydrin and 3
      substituted/unsubstituted indoles using [Hbim]BF4 ionic liquid in excellent
      yields. The method was also used for the synthesis of novel indene-1,3(2H)-denies
      derivatives. 

PMID- 24455298
TI  - Drug utilization study in ophthalmology outpatients at a tertiary care teaching
      hospital.
AB  - In view of the advancement in drug development and availability of new ocular
      therapeutics in the discipline of ophthalmology, we attempted to study the drug
      utilization and describe the prescribing practices of ophthalmologists in a
      tertiary care teaching hospital. Method. A prospective, cross-sectional,
      observational study was conducted on patients attending Outpatient Department of
      Ophthalmology for curative complaints. Prescriptions of 600 patients treated were
      analyzed by the WHO prescribing indicators and additional indices. Results.
      Analysis showed that the average number of drugs per prescription was 1.49.
      Percentage of drugs prescribed by generic name was 2.35%. Percentage of
      encounters with antibiotics was 44.83%. Percentage of drugs prescribed from
      National Essential drug list (NEDL)/National Formulary of India (NFI) was 19.48%.
      Patient's knowledge of correct dosage was 93.83%. Antimicrobial agents were the
      most commonly prescribed drugs followed by antiallergy drugs and ocular
      lubricants. Fluoroquinolones accounted for 60% of the total antimicrobial drugs,
      of which gatifloxacin was the most frequently prescribed fluoroquinolone.
      Conclusion. The study indicated an awareness of polypharmacy, but showed ample
      scope for improvement in encouraging the ophthalmologists to prescribe by generic
      name and selection of essential drugs from NEDL/NFI. 

PMID- 24455299
TI  - Antiapoptotic effect of simvastatin ameliorates myocardial ischemia/reperfusion
      injury.
AB  - Background. Myocardial ischemial reperfusion represents a clinically relevant
      problem associated with thrombolysis, angioplasty, and coronary bypass surgery.
      Injury of myocardium due to ischemial reperfusion includes cardiac contractile
      dysfunction, arrhythmias, and irreversible myocytes damage. These changes are
      considered to be the consequence of imbalance between the formation of oxidants
      and the availability of endogenous antioxidants in the heart. Objective. This
      study was undertaken to investigate the potential role of Simvastatin in the
      amelioration of myocardial I/R injury induced by ligation of coronary artery in a
      rat model. Materials and Methods. Adult male Swiss Albino rats were randomized
      into 4 equal groups. Group (1): sham group: rats underwent the same anesthetic
      and surgical procedures as those in the control group except ligation of LAD
      coronary artery, group (2): control group: rats were subjected to regional
      ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary
      artery, group (3): control vehicle group: rats received vehicle of Simvastatin
      (normal saline) via IP injection and were subjected to regional ischemia for 25
      min and reperfusion for 2 hours by ligation of LAD coronary artery, group (4):
      Simvastatin treated group: rats were pretreated with Simvastatin 1 mg/kg i.p. 1
      hr before ligation of LAD coronary artery. At the end of experiment (2 hr of
      reperfusion), blood samples were collected from the heart for the measurement of
      plasma level of cardiac troponin I (cTnI). After that the heart was harvested and
      divided into 3 parts; one part was used for measurement of apoptosis, another
      part was homogenized for the measurement of tissue tumor necrosis factor- alpha
      (TNF- alpha ), interleukin-1 beta (IL-1 beta ), interleukin-6, monocyte
      chemoattractant protein-1, and macrophage inflammatory protein-1 alpha , and the
      last part for histopathology study. Results. Compared with the sham group, levels
      of myocardial TNF- alpha and IL-1 beta , IL-6, MCP-1, and MIP-1 alpha and plasma
      cTnI were increased (P < 0.05). Histologically, all rats in control group showed
      significant (P < 0.05) cardiac injury. Furthermore, all rats in control group
      showed significant (P < 0.05) apoptosis. Simvastatin significantly counteracted
      the increase in myocardium level of TNF- alpha , IL-1B, IL-6, MCP-1 and MIP-1
      alpha , plasma cTnI, and apoptosis (P < 0.05). Histological analysis revealed
      that Simvastatin markedly reduced (P < 0.05) the severity of heart injury in the
      rats that underwent LAD ligation procedure. Conclusions. The results of the
      present study reveal that Simvastatin may ameliorate myocardial I/R injury in
      rats via interfering with inflammatory reactions and apoptosis which were induced
      by I/R injury. 

PMID- 24455300
TI  - What factors facilitate good learning experiences in clinical studies in nursing:
      bachelor students' perceptions.
AB  - Clinical studies constitute 50% of the bachelor program in nursing education in
      Norway, and the quality of these studies may be decisive for the students'
      opportunities to learn and develop their professional competences. The aim of
      this study was to explore what bachelor students' in nursing perceived to be
      important for having good learning experiences in clinical studies. Data was
      collected in a focus group interview with eight nursing students who were in the
      last year of the educational program. The interview was transcribed verbatim, and
      qualitative content analysis was used for exploring and interpreting the content
      of the interview text. One main theme emerged from the analysis: "being in a
      vulnerable and exposed position characterized by conflicting needs." Four
      categories were found: "aspects related to the clinical setting", "aspects
      related to the nurse supervisor," "aspects related to the student," and "aspects
      related to the student-supervisor relationship". The findings revealed that the
      students' learning experiences and motivation were related to individual,
      relational, and organizational aspects. The students highlighted their own as
      well as their supervisors' attitudes and competences and the importance of
      positive relationships. In addition, feeling welcomed, included, and valued in
      the ward improved their motivation, self-confidence, and self-respect. 

PMID- 24455301
TI  - The Role of BNP and CRP in Predicting the Development of Atrial Fibrillation in
      Patients Undergoing Isolated Coronary Artery Bypass Surgery.
AB  - Objective. To evaluate the association of BNP and CRP with the development of
      postoperative atrial fibrillation following coronary artery bypass grafting
      surgery. Methods. The series consists of 125 patients (aged 65 +/- 9 years), who
      underwent isolated CABG-surgery. BNP and CRP levels were measured pre- and 24
      hours postoperatively and their correlation to the development of postoperative
      AF was analyzed. Results. Forty-four patients (35%) developed AF postoperatively.
      They were significantly older (68 +/- 8 versus 63 +/- 9, P = 0.01) and
      predominantly nonsmokers (18% versus 46%, P = 0.004), compared to the non-AF
      cases. In addition they showed significant higher preoperative mean BNP levels of
      629 versus 373 pg/mL (P = 0.019). Postoperative BNP levels were significantly
      higher in both groups (AF-group: 1032 pg/mL versus non-AF group: 705 pg/mL; P <
      0.001), while there was a trend of more increased postoperative levels in AF
      cases (P = 0.065). AF-episodes appeared significantly more frequent in the two
      highest quartiles of BNP levels with 44% (P = 0.035). On the contrary pre- and
      postoperative CRP levels were not associated with AF. Multivariable analysis
      revealed only increased preoperative BNP levels as independent predictor for
      postoperative AF (P = 0.036). Conclusion. Elevated preoperative BNP serum levels
      are associated with the development of post-CABG AF, while CRP does not seem to
      be influential. 

PMID- 24455302
TI  - Retracted: intracoronary adenosine versus intravenous adenosine during primary
      PCI for ST-elevation myocardial infarction: which one offers better outcomes in
      terms of microvascular obstruction?

PMID- 24455303
TI  - Hybrid surgical and catheter treatment for atrial fibrillation.
AB  - Advances in surgery for atrial fibrillation from cut and sew technique to
      thoracoscopy and new energy source have enabled minimally invasive approach which
      avoids median sternotomy and cardiopulmonary bypass. However, minimally invasive
      approach is unable to match the outcome of classic surgical technique due to
      difficulty in creating some of linear ablation lines. Hybrid procedure using
      catheter mapping and ablation in addition to minimally invasive surgical ablation
      has gained interest to combine the advantages of both procedures. No large study
      has been conducted to date comparing this new technique to other existing
      treatments. The aim of this paper is to review the data on hybrid procedure for
      atrial fibrillation and assess its early outcome and efficacy. 

PMID- 24455304
TI  - Increased Resistance of Breast, Prostate, and Embryonic Carcinoma Cells against
      Herpes Simplex Virus in Three-Dimensional Cultures.
AB  - In previous studies we found that uveal melanoma cells grown in extracellular
      matrix (ECM)-containing three-dimensional (3D) cultures have increased resistance
      against herpes simplex virus type 1 (HSV-1)-mediated destruction relative to
      cells cultured without ECM. Using additional tumor cell types including MB-231
      human breast cancer cells, PC-3 human prostate cancer cells, and P19 mouse
      embryonal carcinoma cells, we show here that tumor cell lines other than melanoma
      are also more resistant to HSV-1-mediated destruction in 3D cultures than cells
      grown in 2D. We also demonstrate here that one mechanism responsible for the
      increased resistance of tumor cells to HSV-1 infection in 3D cultures is an ECM
      mediated inhibition of virus replication following virus entry into cells. These
      findings confirm and extend previous observations related to the role of the ECM
      in tumor resistance against HSV-1 and may lead to improved strategies of
      oncolytic virotherapy. 

PMID- 24455305
TI  - The role of magnetic resonance imaging in preoperative planning for patients
      undergoing therapeutic mammoplasty.
AB  - Background. Assessment of the ratio between tumour volume and breast volume in
      therapeutic mammoplasty is paramount. Traditionally based on clinical assessment
      and conventional breast imaging, the role of breast magnetic resonance imaging
      (MRI) in this context has not been established. Methods. Data was collected from
      all women undergoing therapeutic mammoplasty (TM) between 2006 and 2011. Each
      case was discussed at an MDT where MRI was considered to facilitate surgical
      planning. The contribution of MRI to disease assessment and surgical outcome was
      then reviewed. Results. 35 women underwent TM, 15 of whom had additional MRI. 33%
      of patients within the MRI subgroup had abnormalities not seen on either
      mammography or USS. Of those undergoing MRI, 1/15 patients required completion
      mastectomy versus 3 patients requiring completion mastectomy and 1 patient
      requiring further wide local excision (4/20) in the conventional imaging group.
      No statistical difference was seen between size on MRI and size on mammography
      versus final histological size, but a general trend for greater correlation
      between size on MRI and final histological size was seen. Conclusion. MRI should
      be considered in selected patients undergoing therapeutic mammoplasty. Careful
      planning can identify those who are most likely to benefit from MRI, potentially
      reducing the need for further surgery. 

PMID- 24455306
TI  - Identification, Evaluation, and Treatment of Patients with Hereditary Cancer Risk
      within the United States.
AB  - Recognizing the importance of identifying patients at high risk for inherited
      cancer predisposition, the United States Preventive Services Task Force (USPSTF)
      has outlined specific family history patterns associated with an increased risk
      for BRCA mutations. However, national data indicate a need to facilitate the
      ability of primary care providers to appropriately identify high risk patients.
      Once a patient is identified as high risk, it is necessary for the patient to
      undergo a detailed genetics evaluation to generate a differential diagnosis,
      determine a cost-effective genetic testing strategy, and interpret results of
      testing. With identification of inherited predisposition, risk management
      strategies in line with national guidelines can be implemented to improve patient
      outcomes through cancer risk reduction and early detection. As use of genetic
      testing increasingly impacts patient outcomes, the role of primary care providers
      in the identification and care of individuals at high risk for hereditary cancer
      becomes even more important. Nevertheless it should be acknowledged that primary
      care providers face many competing demands and challenges to identify high risk
      patients. Therefore initiatives which promote multidisciplinary and coordinated
      care, potentially through academic-community partnerships, may provide an
      opportunity to enhance care of these patients. 

PMID- 24455307
TI  - The effect of autologous platelet-rich plasma on bronchial stump tissue
      granulation after pneumonectomy: experimental study.
AB  - Objectives. Recent advances in perioperative management, antibiotics, and
      surgical materials, including mechanical staplers, have decreased the operative
      risk of pulmonary resection. However, bronchopleural fistula can still occur in
      some instances, the occurrence often being lethal. This study investigated
      whether platelet-rich plasma (PRP) promotes granulation of the bronchial stump
      after pneumonectomy. Methods. Ten pigs were randomized into two groups: (A)
      control or non-PRP group (pneumonectomy) and (B) PRP group (pneumonectomy and PRP
      application). PRP was obtained by spinning down the animal's own blood and
      collecting the buffy coat containing platelets and white blood cells. Results.
      Increased platelet concentration triggered the healing process. The percentage of
      granulation tissue formed at the stumps was significantly higher in the PRP group
      of animals. This observation was confirmed when statistical analysis using Mann
      Whitney U test was performed (P = 0.0268). Conclusions. PRP is easily produced
      with minimal basic equipment and is useful in accelerating granulation of the
      bronchial stump, although the timing and optimum number of applications in humans
      require further study. Autologous PRP is a safe, feasible, and reliable new
      healing promoter with potential therapeutic effects. 

PMID- 24455308
TI  - Outcomes of diabetic and nondiabetic patients undergoing general and vascular
      surgery.
AB  - Aims. Preoperative diabetic and glycemic screening may or may not be cost
      effective. Although hyperglycemia is known to compromise surgical outcomes, the
      effect of a diabetic diagnosis on outcomes is poorly known. We examine the effect
      of diabetes on outcomes for general and vascular surgery patients. Methods. Data
      were collected from the Michigan Surgical Quality Collaborative for general or
      vascular surgery patients who had diabetes. Primary and secondary outcomes were
      30-day mortality and 30-day overall morbidity, respectively. Binary logistic
      regression analysis was used to identify risk factors. Results. We identified
      177,430 (89.9%) general surgery and 34,006 (16.1%) vascular surgery patients.
      Insulin and noninsulin diabetics accounted for 7.1% and 9.8%, respectively.
      Insulin and noninsulin dependent diabetics were not at increased risk for
      mortality. Diabetics are at a slight increased odds than non-diabetics for
      overall morbidity, and insulin dependent diabetics more so than non-insulin
      dependent. Ventilator dependence, 10% weight loss, emergent case, and ASA class
      were most predictive. Conclusions. Diabetics were not at increased risk for
      postoperative mortality. Insulin-dependent diabetics undergoing general or
      vascular surgery were at increased risk of overall 30-day morbidity. These data
      provide insight towards mitigating poor surgical outcomes in diabetic patients
      and the cost effectiveness of preoperative diabetic screening. 

PMID- 24455310
TI  - Microglia in neuronal circuits.

PMID- 24455309
TI  - Methylcobalamin: a potential vitamin of pain killer.
AB  - Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to
      treat some nutritional diseases and other diseases in clinic, such as Alzheimer's
      disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal
      protection by promoting regeneration of injured nerves and antagonizing glutamate
      induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl
      may have potential analgesic effects in experimental and clinical studies. For
      example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain
      and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of
      injured nerves, and inhibited ectopic spontaneous discharges of injured primary
      sensory neurons. This review aims to summarize the analgesic effect and
      mechanisms of MeCbl at the present. 

PMID- 24455312
TI  - Development and evaluation of gastroretentive floating tablets of an
      antihypertensive drug using hydrogenated cottonseed oil.
AB  - The aim of the present work was to develop a gastroretentive floating tablet of
      Atenolol and investigate the effects of both hydrophilic and hydrophobic
      retardant on in vitro release. Atenolol is an antihypertensive drug with an oral
      bioavailability of only 50% because of its poor absorption from lower
      gastrointestinal tract. The floating tablets of Atenolol were prepared to
      increase the gastric retention, to extend the drug release, and to improve the
      bioavailability of the drug. The floating tablets were formulated using
      hydrophilic polymers as Hydroxy propyl methyl cellulose (HPMC K4M and HPMC K15M),
      hydrophobic retardant as a hydrogenated cottonseed oil (HCSO), and sodium
      bicarbonate as a gas generating agent to reduce floating lag time. The formulated
      tablets were evaluated for the quality control tests such as weight variation,
      hardness, friability, swelling index, floating lag time, and total floating time.
      The in vitro release study of the tablets was performed in 0.1 N HCl as a
      dissolution media. The results of the present study clearly indicates the
      promising potential of Atenolol floating system as an alternative to the
      conventional dosage and other sustained release formulations. The study also
      revealed the effectiveness of HCSO as retardant in combination with HPMC. 

PMID- 24455311
TI  - Ipsilateral and contralateral auditory brainstem response reorganization in
      hemispherectomized patients.
AB  - BACKGROUND: Cortical hemispherectomy leads to degeneration of ipsilateral
      subcortical structures, which can be observed long term after the operation.
      Therefore, reorganization of the brainstem auditory pathway might occur. The aim
      of this study was to assess reorganization of brainstem auditory pathways by
      measuring the auditory brainstem response (ABR) in long-term hemispherectomized
      patients. METHODS: We performed bilateral monaural stimulation and measured
      bilateral ABR in 8 patients ~20 years after hemispherectomy and 10 control
      subjects. Magnetic resonance imaging (MRI) was performed in patients to assess
      structural degeneration. RESULTS: All patients showed degenerated ipsilateral
      brainstem structures by MRI but no significant differences in bilateral recording
      ABR wave latencies. However, nonsurgical-side stimulation elicited significantly
      longer wave V latencies compared to surgical-side stimulation. Differences in
      bilateral ABR were observed between hemispherectomized patients and control
      subjects. Waves III and V latencies elicited by nonsurgical-side stimulation were
      significantly longer than those in control subjects; surgical-side stimulation
      showed no significant differences. CONCLUSIONS: (1) Differences in ABR latency
      elicited by unilateral stimulation are predominantly due to bilateral brainstem
      auditory pathway activity rather than to changes in brainstem volume; (2) ABR
      Waves III and V originate predominantly in the contralateral brainstem; and (3)
      subcortical auditory pathways appear to reorganize after long term
      hemispherectomy.

PMID- 24455313
TI  - Design and characterization of double layered mucoadhesive system containing
      bisphosphonate derivative.
AB  - The objective of this study is to evaluate the effect of formulation variables on
      different evaluation properties such as cumulative percentage release and
      swelling index in development of two layered buccal mucoadhesive system
      consisting of a highly water soluble drug risedronate sodium. The mucoadhesive
      systems were developed with varied concentrations of the polymers (1-2%) using
      plasticizer/permeation enhancer (25-50% w/w of polymer). Two layered films
      comprised of risedronate sodium with chitosan (85% deacetylated) and
      hydroxypropylmethyl cellulose (HPMC 4KM) interpolymer complex of different ratios
      were prepared by solvent casting method. An impermeable backing membrane of ethyl
      cellulose was incorporated into the films. The study shows the effect of
      multipolymeric films on the release of a bisphosphonates derivative. The
      optimized formulations showed films with uniform drug content (90.91 +/- 0.17
      105.53% +/- 2.15), thickness (0.22 +/- 0.01 mm to 0.31 +/- 0.06 mm),
      mucoadhesivity (26 +/- 3.61-42.33 +/- 2.82 g), and controlled drug release
      profile up to a period of 10 hours. The films were also studied for swelling
      index, moisture uptake, viscosity, folding endurance, water vapor transmission
      rate, and mucoadhesive time. 

PMID- 24455314
TI  - Reduced life expectancy model for effects of long term exposure on lethal
      toxicity with fish.
AB  - A model based on the concept of reduction in life expectancy (RLE model) as a
      result of long term exposure to toxicant has been developed which has normal life
      expectancy (NLT) as a fixed limiting point for a species. The model is based on
      the equation (LC50 = a ln(LT50) + b) where a and b are constants. It was
      evaluated by plotting ln LT50 against LC50 with data on organic toxicants
      obtained from the scientific literature. Linear relationships between LC50 and ln
      LT50 were obtained and a Calculated NLT was derived from the plots. The
      Calculated NLT obtained was in good agreement with the Reported NLT obtained from
      the literature. Estimation of toxicity at any exposure time and concentration is
      possible using the model. The use of NLT as a reference point is important since
      it provides a data point independent of the toxicity data set and limits the data
      to the range where toxicity occurs. This novel approach, which represents a
      departure from Haber's rule, can be used to estimate long term toxicity from
      limited available acute toxicity data for fish exposed to organic biocides. 

PMID- 24455315
TI  - Paraben levels in an urban community of Western Canada.
AB  - With effective antibacterial and antifungal properties, commercially used
      parabens are synthetic compounds widely utilized as preservatives in cosmetics,
      personal care products, pharmaceuticals, and as an additive in some foodstuffs.
      While long regarded as relatively safe and nontoxic, recent research has
      demonstrated xenoestrogenic properties of anthropogenic parabens with early
      evidence that paraben exposure may be linked to breast cancer, thyroid
      dysfunction, allergy, and obesity. In an attempt to determine the prevalence of
      paraben exposure in a Canadian urban community, a sample of convenience was done
      by measuring urinary levels of methyl, ethyl, propyl, butyl, and isobutyl
      parabens (MP, EP, PP, BP, and IP) in 39 consecutive patients in an Alberta
      primary care clinic. In 28 female patients including 9 pregnant women, the median
      urinary levels (in MU g/L) were 25.45 for MP, 10.17 for EP, 2.80 for PP, 0.30 for
      BP, and 0.24 for IP. In 11 male patients, the median urinary levels (in MU g/L)
      were 25.95 for MP, 10.37 for EP, 3.09 for PP, 0.35 for BP, and 0.22 for IP.
      Especially high urinary paraben levels were reported in a few patients, with the
      highest urinary concentrations (in MU g/L) reported as 966.46 for MP, 220.6 as
      EP, and 612.73 for PP. It is evident that exposure to assorted parabens is a
      routine event for many if not most individuals, including pregnant women, in
      urban Alberta, Canada. 

PMID- 24455316
TI  - A minimal-invasive metabolic test detects malignant hyperthermia susceptibility
      in a patient after sevoflurane-induced metabolic crisis.
AB  - Malignant hyperthermia is a rare but life-threatening complication of general
      anesthesia in predisposed patients usually triggered by potent inhalation
      anesthetics and/or the depolarizing muscle relaxant succinylcholine. The authors
      present a case of delayed sevoflurane-induced malignant hyperthermia in a 21-year
      old male patient that was sufficiently treated by discontinuation of trigger
      agent application and dantrolene infusion. After surviving an MH episode
      diagnostic procedures are indicated to increase patient safety. In the presented
      case, the use of a novel minimal-invasive metabolic test with intramuscular
      injection of halothane and caffeine successfully confirmed MH susceptibility and
      hence might be an alternative for invasive in vitro contracture testing in
      selected cases. 

PMID- 24455317
TI  - Bruxism associated with anoxic encephalopathy: successful treatment with
      baclofen.
AB  - Introduction. Bruxism is a movement disorder characterized by grinding and
      clenching of the teeth. Etiology of bruxism can be divided into three groups:
      psychosocial factors, peripheral factors, and pathophysiological factors.
      Methods. The clinical investigation was conducted at King Khaled Hospital in
      Hail, Saudi Arabia, in 2012. Results. A 16-year-old Saudi female was brought to
      the hospital in a comatose state and with generalized convulsive seizures
      secondary to acute anoxic encephalopathy. In the third week of hospitalization,
      while still in a state of akinetic mutism, she developed incessant bruxism which
      responded favorably to a GABA receptor agonist (baclofen). Conclusion. Our data
      support the hypothesis that bruxism emanates from imbalance or dysregulation of
      the neurotransmitter system. Larger scale studies will be needed to confirm this
      hypothesis. 

PMID- 24455318
TI  - Restoration of endodontically treated molars using all ceramic endocrowns.
AB  - Clinical success of endodontically treated posterior teeth is determined by the
      postendodontic restoration. Several options have been proposed to restore
      endodontically treated teeth. Endocrowns represent a conservative and esthetic
      restorative alternative to full coverage crowns. The preparation consists of a
      circular equigingival butt-joint margin and central retention cavity into the
      entire pulp chamber constructing both the crown and the core as a single unit.
      The case reports discussed here are moderately damaged endodontically treated
      molars restored using all ceramic endocrowns fabricated using two different
      systems, namely, CAD/CAM and pressed ceramic. 

PMID- 24455319
TI  - Sinus lift and transantral approach to root fragment removal.
AB  - The aim of this case report is to present a case of root fragment removal during
      planned sinus lift procedure. After failed molar tooth extraction, we chose to
      retrieve the residual root apex with transantral approach not to damage
      excessively bone volume. Without changing primary implant rehabilitation purpose,
      the fragment removal procedure was performed prior to implant placement during
      necessary sinus lift surgery. Higher visibility of surgical field was achieved.
      The root fragment residual was removed without an additional surgery appointment
      avoiding postoperative discomfort. The goal is to underline the importance of
      being able to change planning during intrasurgical complications. It is most
      appropriate to operate with safe and simple procedures to reduce surgical
      discomfort for the patient. 

PMID- 24455320
TI  - Management of complex root canal curvature of bilateral radix entomolaris: three
      dimensional analysis with cone beam computed tomography.
AB  - The meticulous knowledge of anatomic characteristics and their variations is
      essential for the clinician. Radix entomolaris (RE) is one such anomaly where an
      extra root is present on the distolingual aspect of the mandibular first molar.
      18-year-old patient was referred for the root canal treatment of mandibular right
      and left first molars. Intraoral periapical radiograph revealed additional
      periodontal spacing crossing distal root of 36. A CBCT was advised and it
      confirmed the presence of extra roots both in 36 and 46. CBCT is useful in
      endodontics as it aids in the identification of essential anatomic structures and
      determination of radius and angle of root canal curvature which is linked to
      fracture of the instrument. The classical triangular access cavity was modified
      to a trapezoidal form to locate the extra canal. All canals were instrumented
      with controlled memory nickel titanium instruments and obturation was done with
      single cone technique. 

PMID- 24455321
TI  - Combined Orthodontic and Surgical Approach in the Correction of a Class III
      Skeletal Malocclusion with Mandibular Prognathism and Vertical Maxillary Excess
      Using Bimaxillary Osteotomy.
AB  - For patients whose orthodontic problems are so severe that neither growth
      modification nor camouflage offers a solution, surgery to realign the jaws or
      reposition dentoalveolar segments is the only possible treatment. Surgery is not
      a substitute for orthodontics in these patients. Instead, it must be properly
      coordinated with orthodontics and other dental treatments to achieve good overall
      results. Dramatic progress in recent years has made it possible for combined
      surgical orthodontic treatment to be carried out successfully for patients with a
      severe dentofacial problem of any type. This case report provides an overview of
      the current treatment methodology in managing a combination of asymmetrical
      mandibular prognathism and vertical maxillary excess. 

PMID- 24455322
TI  - Iatrogenic inflammatory fibrosis of hard palate in a 13-year-old female patient.
AB  - Palatal swellings are rare in children and the incidence differs from that of the
      adult counterparts. When the palatal swellings do arise in children, they usually
      are palatal abscess from periapical region, and few cases like pleomorphic
      adenoma in young adults have also been reported. But inflammatory fibrosis of
      palate in children is a rare occurrence. Inflammatory fibrosis is formation of
      excess fibrous connective tissue in an organ or tissue, as a reparative or
      reactive process. This report describes an unusual case of iatrogenic
      inflammatory fibrosis on the palate due to extraction of tooth number 22 in a 13
      year-old female patient. The patient presented with a single large well
      circumscribed oval palatal swelling that was soft, fluctuant, not fixed, and
      nontender. Surgical excision of the lesion was done and it was sent for
      histopathological assessment. The biopsy showed fibrous tissue with collagen
      fibers, spindle shaped fibroblasts, neovascularization, RBCs, chronic
      inflammatory cells, and traces of salivary gland and nerve tissue. 

PMID- 24455323
TI  - Multifocal Epithelial Hyperplasia of Oral Cavity Expressing HPV 16 Gene: A Rare
      Entity.
AB  - Focal epithelial hyperplasia is a rare contagious disease caused by human
      papilloma virus. Usually HPV involves either cutaneous or mucosal surfaces,
      whereas concomitant mucocutaneous involvement is extremely rare. We report such a
      unique case of multifocal epithelial hyperplasia involving multiple sites of oral
      cavity along with skin lesions in a 65-year-old female. We also discuss the
      probable multifactorial etiology and variable clinical presentations of the
      lesions, including evidence of HPV 16 expression, as detected by polymerase chain
      reaction. The present report illustrates the need for careful examination and
      prompt diagnosis of the disease, as it might be associated with high risk
      genotypes such as HPV 16 and 18. 

PMID- 24455324
TI  - Ulcerative lichen planus in childhood.
AB  - Lichen planus (LP) is a chronic inflammatory mucocutaneous condition which is
      relatively common in adults but rarely affects children. The present study is a
      report on an unusual case of ulcerative oral LP involving the dorsum of tongue in
      a 12-year-old boy. Patient complained of painful oral lesion on the tongue which
      was burning in nature and obstructing talking and eating spicy foods. On
      intraoral examination, a white ulcerative lesion on the dorsum of tongue was
      observed. Diagnosis was made based on clinical examination and histopathological
      features. We instituted local treatment and patient responded well to the
      treatment. Although rarely reported in childhood, lichen planus should be
      considered in a differential diagnosis of hyperkeratotic, reticular, and
      ulcerative lesions of the oral mucosa in children. 

PMID- 24455325
TI  - Limited mouth opening secondary to diffuse systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a relatively rare condition with an immunologically
      mediated pathogenesis. For reasons that are not clearly understood, dense
      collagen is deposited in the connective tissues of the body in extraordinary
      amounts. Although its dramatic effects are seen in association with the skin, the
      disease is often quite serious with visceral organ involvement. We describe a
      case of limited mouth opening secondary to diffuse SSc, improvement in mouth
      opening with passive jaw stretch exercises, and the challenges involved in
      performing dental procedures for such patients. 

PMID- 24455326
TI  - Exophytic parietal skin metastases of renal cell carcinoma.
AB  - The common sites for metastasis of renal cell carcinoma are lung, kidney, adrenal
      glands, liver, and contralateral kidney. We report an unusual case of cutaneous
      metastasis of renal cell carcinoma in a 68-year-old woman who was treated for
      renal cell carcinoma with partial right nephrectomy and multikinase angiogenesis
      inhibitor (sunitinib) 10 years ago. 

PMID- 24455327
TI  - Traumatic implantation: a novel aetiology in the development of peritoneal
      mesothelioma.
AB  - Peritoneal mesothelioma is a rare intra-abdominal malignancy. Its aetiology has
      been thought to be due to either inhalation or ingestion of asbestos particles.
      We present a case of peritoneal mesothelioma developing as a result of a novel
      third route and the inoculation of fibres into the peritoneal cavity by
      penetrating trauma and direct transport. This case report highlights the
      important long term consequences of penetrating abdominal trauma and the need for
      vigilance in undertaking peritoneal toilet. 

PMID- 24455328
TI  - Bedside ultrasound in workup of self-inserted headset cable into the penile
      urethra and incidentally discovered intravesical foreign body.
AB  - There are multiple reports of foreign bodies inserted into the lower urinary
      tract. We report the case of an incidentally discovered foreign body identified
      within the bladder in a male patient presenting with a radio antenna protruding
      from the urethra attached to a head set. On workup patient was found to have an
      additional foreign body within the bladder and second radiolucent object within
      the urethra. This case demonstrates the importance of complete evaluation of the
      lower urinary tract during workup of inserted foreign bodies and the value of the
      bedside ultrasound as a diagnostic tool in distinguishing between rectal and
      genitourinary tract insertion. 

PMID- 24455329
TI  - A case report of spontaneous closure of a posttraumatic arterioportal fistula.
AB  - As the indications for the nonoperative management (NOM) of hepatic injury have
      expanded, the incidence of complications of NOM has increased. Among such
      complications, arterioportal fistula (APF) formation is rare, although dangerous,
      due to the potential for portal hypertension. Embolization is performed in APF
      patients with clinical signs suggestive of portal hypertension. Meanwhile, no
      indications for treatment have been established in APF patients without symptoms,
      as the natural history of posttraumatic APF is not well understood. We herein
      report the case of a 35-year-old female with severe hepatic injury (Grade IV on
      the Organ Injury Scale of the American Association for the Surgery of Trauma) due
      to a traffic accident. Her hemodynamic state remained stable, and an enhanced CT
      scan obtained on admission showed no extravasation of contrast medium,
      pseudoaneurysm formation, or APF; therefore, NOM was selected. Although the
      patient's physical condition was stable, an enhanced CT scan obtained 13 days
      after the injury showed APF in segment 8 of the liver. Although embolization was
      considered, the APF was not accompanied by portal dilatation suggestive of portal
      hypertension; hence, strict observation was selected. Consequently, follow-up CT
      performed on day 58 after the injury revealed spontaneous closure of the APF. 

PMID- 24455330
TI  - Metastatic insulinoma managed with radiolabeled somatostatin analog.
AB  - Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin
      and associated hypoglycemia are hallmark features of this disease. Diagnosis can
      be made through demonstration of hypoglycemia and elevated plasma levels of
      insulin or C-Peptide. Metastatic disease can be detected through computerized
      tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission
      tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to
      document metastatic disease but also as a predictive marker of the benefit from
      therapy with radiolabeled somatostatin analog. Unresectable metastatic
      insulinomas may present as a major therapeutic challenge for the treating
      physician. When feasible, resection is the mainstay of treatment. Prevention of
      hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors.
      Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have
      been used for glycemic control yielding temporary and inconsistent results.
      Sandostatin and its long-acting depot forms have occasionally been used in the
      treatment of Octreoscan-positive insulinomas. Herein, we report a case of
      metastatic insulinoma with very difficult glycemic control successfully treated
      with the radiolabeled somatostatin analog lutetium ((177)LU). 

PMID- 24455331
TI  - Autosomal dominant pseudohypoaldosteronism type 1 in an infant with salt wasting
      crisis associated with urinary tract infection and obstructive uropathy.
AB  - Type 1 pseudohypoaldosteronism (PHA1) is a salt wasting syndrome caused by renal
      resistance to aldosterone. Primary renal PHA1 or autosomal dominant PHA1 is
      caused by mutations in mineralocorticoids receptor gene (NR3C2), while secondary
      PHA1 is frequently associated with urinary tract infection (UTI) and/or urinary
      tract malformations (UTM). We report a 14-day-old male infant presenting with
      severe hyperkalemia, hyponatremic dehydration, metabolic acidosis, and markedly
      elevated serum aldosterone level, initially thought to have secondary PHA1 due to
      the associated UTI and posterior urethral valves. His serum aldosterone remained
      elevated at 5 months of age, despite resolution of salt wasting symptoms.
      Chromosomal microarray analysis revealed a deletion of exons 3-5 in NR3C2 in the
      patient and his asymptomatic mother who also had elevated serum aldosterone
      level, confirming that he had primary or autosomal dominant PHA1. Our case raises
      the possibility that some patients with secondary PHA1 attributed to UTI and/or
      UTM may instead have primary autosomal dominant PHA1, for which genetic testing
      should be considered to identify the cause, determine future recurrence risk, and
      possibly prevent the life-threatening salt wasting in a subsequent family member.
      Future clinical research is needed to investigate the potential overlapping
      between secondary PHA1 and primary autosomal dominant PHA1. 

PMID- 24455332
TI  - Chemotherapy-induced regression of an adrenocorticotropin-secreting pituitary
      carcinoma accompanied by secondary adrenal insufficiency.
AB  - Purpose. Adrenocorticotropin- (ACTH-) secreting pituitary carcinomas are rare and
      require multimodality treatment. The aim of this study was to report the response
      to various therapies and discuss the potential development of secondary adrenal
      insufficiency with cytotoxic chemotherapy. Methods. This report describes a man
      with a large silent corticotroph adenoma progressing to endogenous
      hypercortisolism and metastatic ACTH-secreting pituitary carcinoma over a period
      of 14 years. Results. Seven years after initial presentation, progressive tumor
      enlargement associated with the development of hypercortisolism mandated multiple
      pituitary tumor debulking procedures and radiotherapy. Testing of the Ki-67
      proliferation index was markedly high and he developed a hepatic metastasis.
      Combination therapy with cisplatin and etoposide resulted in a substantial
      reduction in tumor size, near-complete regression of his liver metastasis, and
      dramatic decrease in ACTH secretion. This unexpectedly resulted in symptomatic
      secondary adrenal insufficiency. Conclusions. This is the first reported case of
      secondary adrenal insufficiency after use of cytotoxic chemotherapy for
      metastatic ACTH-secreting pituitary carcinoma. High proliferative indices may be
      predictive of dramatic responses to chemotherapy. Given the potential for such
      responses, the development of secondary adrenal insufficiency may occur and
      patients should be monitored accordingly. 

PMID- 24455333
TI  - Aspergillus thyroiditis: a complication of respiratory tract infection in an
      immunocompromised patient.
AB  - A 59-year-old male with past medical history significant for non-Hodgkin's
      lymphoma status after chemotherapy presented with acute onset of neck pain,
      odynophagia, and dysphagia associated with subjective fever, chills, and dyspnea.
      Physical findings included a temperature of 38.4 degrees C, hypertension, and
      tachycardia. Patient was found to have anterior neck tenderness. Laboratory
      evaluation revealed neutropenia. The patient was started on empiric antibacterial
      and antiviral therapy and continued on home prophylactic antifungal treatment.
      Thyroid function tests revealed overt hyperthyroidism. A thyroid ultrasound
      showed heterogeneous echotexture without discrete nodules. Subacute thyroiditis
      was treated with methylprednisolone, metoprolol, and opiate analgesics. Patient's
      antibacterial, antifungal, and antiviral treatments were broadened. A fine needle
      aspiration was not conducted. The patient's condition deteriorated rapidly over
      his brief hospital course and he expired. Autopsy showed fungal thyroiditis
      secondary to disseminated invasive Aspergillus. This report describes the
      presentation of fungal thyroiditis secondary to disseminated invasive Aspergillus
      originating from the respiratory tract. The authors review the diagnostic
      challenges, pathophysiology, and treatment of this condition. 

PMID- 24455334
TI  - Insulinoma presenting with long-standing depression, primary hypogonadism, and
      sertoli cell only syndrome.
AB  - The aim was to report an unusual case of insulinoma presenting with long-standing
      depression and primary testicular failure. We describe a 34-year-old male with
      clinical, laboratory, and radiologic data consistent with islet cell tumor and
      seminiferous tubule failure primary hypogonadism. The literature is reviewed
      relative to the component of this syndrome, and a possible association is
      discussed. The subject was investigated for a long-standing history of depression
      requiring medical attention because of mental confusion and slurred speech and
      was found to have an insulinoma. He was diagnosed with primary gonadal failure
      and physical examination showed no evidence of dysmorphic features. Chromosomal
      analysis revealed normal 46 XY and testicular biopsy showed Sertoli cell only
      syndrome (SCOS). Biochemistry revealed endogenous hyperinsulinism and histology
      confirmed an islet cell tumor. He remained euglycemic postoperatively and on
      followup. From this report, we emphasize drawing clinicians' attention to the
      possibility of an association between insulinoma and primary testicular failure
      and suggest consideration of this diagnosis in patients with hypergonadotropic
      hypogonadism who may present with infertility. 

PMID- 24455335
TI  - Metronidazole induced liver injury: a rare immune mediated drug reaction.
AB  - Drug induced liver injury (DILI) can result either from dose-dependent direct
      hepatotoxicity or from an unpredictable dose-independent idiosyncratic reaction.
      Incidence of idiosyncratic DILI is estimated to be approximately 10-15 per
      100,000 patient years. Here we report an extremely rare case of metronidazole
      induced delayed immune-allergic hepatocellular liver injury masquerading as
      autoimmune hepatitis. A previously healthy 54-year-old Caucasian male, who was
      treated with metronidazole for Clostridium difficile associated diarrhea,
      presented 3 months later with right upper quadrant abdominal pain. Laboratory
      tests revealed total bilirubin level of 12.7 mg/dL, direct bilirubin of 7.2
      mg/dL, alanine aminotransferase (ALT) of 973 IU/L, aspartate transaminase (AST)
      of 867 IU/L, alkaline phosphatase (AP) of 96 IU/L, and an INR of 1.9, suggestive
      of hepatocellular pattern of injury. A detailed workup for hepatitis revealed no
      other etiology. A clinical diagnosis of metronidazole induced liver injury was
      made. With a persistent rise in his bilirubin and transaminase levels, the
      patient was started on oral prednisone. At the 2-week posthospitalization follow
      up visit, the patient reported a significant improvement in his overall sense of
      being well and liver functions tests trended down substantially (total bilirubin
      7.2 mg/dL, ALT 420 IU/L, AST 276 IU/L, AP 183 IU/L, and INR 1.5). 

PMID- 24455336
TI  - A Case of an Acquired Factor VIII Inhibitor Complicated by Multiple Treatment
      Related Opportunistic Infections and Review of the Literature.
AB  - This case report describes a patient with an idiopathic acquired Factor VIII
      inhibitor and severe bleeding. She was treated with rituximab after failing first
      line treatment with steroids and cyclophosphamide. Two months following rituximab
      treatment, our patient developed a succession of severe opportunistic infections
      requiring intensive care unit admission. Over a period of 12 weeks she required
      treatment for Pseudomonas aeruginosa septicaemia, herpes simplex
      gingivostomatitis and pharyngotonsillitis, clostridium difficile-related
      diarrhoea, systemic cytomegalovirus infection, pneumocystis jiroveci, and
      invasive pulmonary aspergillosis lung infections. After significant
      rehabilitation, the patient was finally discharged following a 5-month admission.
      This case highlights the complexity of balancing a life-threatening condition
      with the side effects of treatment. It also raises the issue of routine
      prophylaxis for immunosuppression in nonmalignant conditions, which will become a
      common dilemma with the expanding indications for rituximab use. 

PMID- 24455337
TI  - Lung adenocarcinoma in a patient with plasmacytoma.
AB  - An increased risk of second malignancy is well recognized in patients treated for
      plasma cell neoplasms. However, second solid tumor is very rare in such patients.
      We report a case of a 68-year-old woman with plasmacytoma who developed lung
      adenocarcinoma. 

PMID- 24455338
TI  - Malignant phyllodes tumor and acute megakaryoblastic leukemia sharing a common
      clonal origin.
AB  - There is a well-known association in male patients between mediastinal germ cell
      tumors (GCT) and hematologic malignancies, with a propensity towards acute
      megakaryoblastic leukemia. These rare malignancies have been shown to share a
      common clonal origin, often deduced from the finding of isochromosome 12p,
      i(12p), in cells from both the solid tumor and the leukemia, and thus are now
      known to represent different manifestations of the same clonal process. We
      treated a young female patient with a malignant phyllodes tumor followed by an
      acute megakaryoblastic leukemia and found several of the same marker chromosomes
      by karyotype analysis of cells from both the tumor and the leukemia implying a
      common clonal origin of the two. To the best of our knowledge, this has not been
      demonstrated in phyllodes tumors before, but indicates that the same type of
      leukemization may occur of this tumor as has been described in mediastinal GCT. 

PMID- 24455339
TI  - Vibrio parahaemolyticus Induced Necrotizing Fasciitis: An Atypical Organism
      Causing an Unusual Presentation.
AB  - Background necrotizing fasciitis (NF) represents a life-threatening bacterial
      infection characterized by a rapid necrosis of deep subcutaneous tissue and facia
      underlying the skin. Despite its lethal nature, NF occurs infrequently, leaving
      many physicians unfamiliar with the disease process, common pathogens, and
      treatment strategies. Here we present a case of NF caused by an unlikely
      organism, Vibrio parahaemolyticus. We highlight the innocuous nature of initial
      presentation and the potentially devastating sequela. 

PMID- 24455340
TI  - Small intestinal obstruction caused by anisakiasis.
AB  - Small intestinal anisakiasis is a rare disease that is very difficult to
      diagnose, and its initial diagnosis is often surgical. However, it is typically a
      benign disease that resolves with conservative treatment, and unnecessary surgery
      can be avoided if it is appropriately diagnosed. This case report is an example
      of small intestinal obstruction caused by anisakiasis that resolved with
      conservative treatment. A 63-year-old man admitted to our department with acute
      abdominal pain. A history of raw fish (sushi) ingestion was recorded. Abdominal
      CT demonstrated small intestinal dilatation with wall thickening and contrast
      enhancement. Ascitic fluid was found on the liver surface and in the Douglas
      pouch. His IgE (RIST) was elevated, and he tested positive for the anti-Anisakis
      antibodies IgG and IgA. Small intestinal obstruction by anisakiasis was highly
      suspected and conservative treatment was performed, ileus tube, fasting, and
      fluid replacement. Symptoms quickly resolved, and he was discharged on the
      seventh day of admission. Small intestinal anisakiasis is a relatively uncommon
      disease, the diagnosis of which may be difficult. Because it is a self-limiting
      disease that usually resolves in 1-2 weeks, a conservative approach is advisable
      to avoid unnecessary surgery. 

PMID- 24455341
TI  - Methicillin Resistant Staphylococcus aureus Prostatic Abscess with Bacteremia.
AB  - Prostatic abscess is traditionally considered a rare disease that is caused by
      Gram-negative bacteria. Methicillin resistant Staphylococcus aureus (MRSA) has
      recently emerged as an important cause of prostatic abscesses. Symptoms are
      nonspecific and include dysuria, urinary frequency, fever, chills, and perineal
      and low back pain. Morbidity and mortality increase with delays in identification
      and proper treatment. We present two cases of community acquired MRSA prostatic
      abscesses with bacteremia. One of these cases may be the first reported septic
      shock fatality resulting from a prostatic abscess source in an immunocompetent
      patient. As the number of community acquired MRSA bacteremia cases increases,
      this potential site of infection should be recognized. 

PMID- 24455342
TI  - Central Nervous System Demyelination in a Charcot-Marie-Tooth Type 1A Patient.
AB  - Introduction. Central nervous system involvement, either clinical or subclinical,
      has been reported mainly in X-linked Charcot-Marie-Tooth (CMT-X) patients. Case
      Presentation. We present the case of a 31-year-old man with a genetically
      confirmed history of CMT1A who developed CNS involvement mimicking multiple
      sclerosis (MS). Clinical, imaging, and laboratory findings suggested an
      autoimmune CNS demyelination. Discussion. Although the simultaneous existence of
      CMT1A and MS could be coincidental we postulate that overexpression of PMP22, the
      target protein in CMT1A, might influence the immunological self-tolerance to CNS
      proteins via molecular mimicry, leading to a CNS autoimmune demyelinating
      disorder. 

PMID- 24455343
TI  - Longitudinally extensive transverse myelitis with intramedullary metastasis of
      small-cell lung carcinoma: an autopsy case report.
AB  - Background. Longitudinally extensive transverse myelitis (LETM) is characterized
      by spinal cord inflammation extending vertically through three or more vertebral
      segments. The widespread use of MRI revealed LETM more frequency than ever. We
      report the case of a patient with pathologically confirmed small-cell lung
      carcinoma metastasis into the spinal cord presenting as LETM. Case Presentation.
      A 74-year-old man developed rapidly progressive sensorimotor disturbance and
      vesicorectal dysfunction. T2-weighted magnetic resonance imaging of the spine
      revealed LETM at the level of from T3 to conus medullaris; gadolinium enhancement
      showed concurrent tumor in the thoracic spinal cord from T10 to T11. Systemic
      survey identified a nodular mass in the lung that was verified as small-cell
      carcinoma. Following initial failed treatment by high-dose steroid, the patient
      underwent an emergent microsurgical tumor resection. Histological examination was
      identical with the lung carcinoma. The patient died of tumor progression at the
      47th day after admission. At autopsy, only changes of edema were found in the
      gray matter of the cord, while tumor cells were not noted in it. Conclusion.
      Metastasis may rarely present symptoms of LETM. Prompt identification of
      underlying etiology by contrast examination and systemic survey is crucial for
      the patient assumed as LETM. 

PMID- 24455344
TI  - Syncope associated with subthalamic nucleus deep brain stimulation in a patient
      with Parkinson's disease.
AB  - In advanced Parkinson's disease (PD), deep brain stimulation (DBS) may be an
      alternative option for the treatment of motor symptoms. Side effects associated
      with subthalamic nucleus (STN) DBS in patients with PD are emerging as the most
      frequent sensory and motor symptoms. DBS-related syncope is reported as extremely
      rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a
      patient with Parkinson's disease. Case report. Sixty-three-year-old female
      patient is followed up with diagnosis of idiopathic Parkinson's disease for 6
      years in our clinic. The patient has undergone STN DBS due to painful dystonia
      and drug resistant tremor. During the operation, when the left STN was stimulated
      at 5 milliampere (mAmp), the patient developed presyncopal symptoms. However,
      when the stimulation was stopped symptoms improved. During the early period after
      the operation, when the right STN was stimulated at 1.3 millivolts (mV), she
      developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS
      may lead to directly autonomic symptoms resulting in syncope during stimulation
      on (stim-on). 

PMID- 24455345
TI  - Symptomatic pneumocephalus associated with lumbar dural tear and reverse
      trendelenburg positioning: a case report and review of the literature.
AB  - Symptomatic pneumocephalus is a rare complication of degenerative lumbar spine
      surgery. This is a case report of a patient who developed transient diplopia
      associated with pneumocephalus following lumbar spine surgery complicated by a
      dural tear. The diplopia improved as the pneumocephalus resolved. Factors
      involved in the development of pneumocephalus include an unintended durotomy and
      intraoperative reverse Trendelenburg positioning that was utilized to decrease
      the risk of postoperative vision loss. When encountering cerebrospinal fluid
      (CSF) leakage intraoperatively, spine surgeons should level the operating table
      until closure of the dural defect to prevent potential complications associated
      with pneumocephalus. If postoperative patients complain of severe headaches or
      display a focal cranial neurologic deficit, then a computed tomography (CT) scan
      of the brain should be ordered and evaluated. Consulting neurologists should be
      aware of the circumstances surrounding this rare complication. 

PMID- 24455346
TI  - Adnexal torsion with dystrophic calcifications in an adolescent: a chronic
      entity?
AB  - Intermittent pelvic pain caused by ovarian cysts in adolescence may be due to
      torsion or partial torsion of the ovary. We present a case of 18-year old
      adolescent with symptomatic left ovarian torsion with calcifications demonstrated
      by pelvic MRI and ultrasonography prior to surgery. The pathologic investigation
      demonstrated dystrophic calcifications. We speculated that the pattern of the
      intermittent pain in the story of the patient and the dystrophic calcifications
      in pathologic investigation which is thought that it might have been potentially
      developed as a result of chronic hypoxia due to intermittent partial torsions
      over a period of two years. 

PMID- 24455347
TI  - Prenatal diagnosis of 4p and 4q subtelomeric microdeletion in de novo ring
      chromosome 4.
AB  - Ring chromosomes are unusual abnormalities that are observed in prenatal
      diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis
      due to abnormal maternal serum screening result in the 16th week of second
      pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out
      ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal
      deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence
      in situ hybridization (FISH). However deletion was not observed in the WHS
      critical region of both normal and ring chromosome 4 by an additional FISH study.
      These results were confirmed by means of array-CGH showing terminal deletions on
      4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross
      anomalia, except two weeks symmetric growth retardation, was present in the fetal
      ultrasonographic examination. According to our review of literature, this is the
      first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4
      without the involvement of WHS critical region. Our report describes the prenatal
      case with a ring chromosome 4 abnormality completely characterized by array-CGH
      which provided complementary data for genetic counseling of prenatal diagnosis. 

PMID- 24455348
TI  - Intracranial subdural hematoma after spinal anesthesia for cesarean section.
AB  - Intracranial subdural hematoma following spinal anesthesia is an infrequent
      occurrence in the obstetric population. Nevertheless, it is a potentially life
      threatening complication. In the majority of the cases, the first clinical
      symptom associated with intracranial subdural bleeding is severe headache, but
      the clinical course may have different presentations. In this report, we describe
      the case of a 38-year-old woman with an acute intracranial subdural hematoma
      shortly after spinal anesthesia for cesarean section. Early recognition of
      symptoms of neurologic impairment led to an emergency craniotomy for hematoma
      evacuation with good recovery of neurologic functions. The possibility of
      subdural hematoma should be considered in any patient complaining of severe
      persistent headache following regional anesthesia, unrelieved by conservative
      measures. Only early diagnosis and an appropriate treatment may avoid death or
      irreversible neurologic damage. 

PMID- 24455349
TI  - Importance of close follow-up in the fetus with premature atrial contractions
      accompanied by atrial septal aneurysm: a case report.
AB  - Rhythms that derive from parts of atria other than the sinus node are called
      premature atrial contractions (PACs). Vast majority of fetal PACs are idiopathic.
      Fetal PACs usually have a good prognosis and disappear spontaneously during
      pregnancy or after delivery. Development of fetal tachycardia or fetal
      bradycardia is rarely reported during follow-up of fetuses diagnosed with PACs.
      To the best of our knowledge, coexistence of tachycardia and bradycardia leading
      to hemodynamic impairment has not yet been reported. We present a fetus diagnosed
      with PACs and atrial septal aneurysm (ASA) on the 23rd week of gestation
      proceeding to fetal bradycardia and fetal tachycardia and consequently
      hemodynamic impairment. We suggest closer follow-up of fetuses with PACs
      accompanied by ASA. 

PMID- 24455350
TI  - Surgical management of the cesarean scar ectopic pregnancy: a case report.
AB  - Cesarean scar pregnancy is one of the rarest forms of ectopic pregnancy. Little
      is known about its incidence and natural history. The diagnosis and treatment of
      cesarean scar pregnancy (CSP) is challenging. The authors reported here a case of
      cesarean scar pregnancy (CSP) with hypovolemic shock that underwent emergency
      laparotomy with resection of ectopic mass. The patient was discharged from the
      hospital without any complications. 

PMID- 24455351
TI  - Velamentous and Furcate Cord Insertion with Placenta Accreta in an IVF Pregnancy
      with Unicornuate Uterus.
AB  - Velamentous and furcate cord insertion with concomitant placenta accreta is a
      very rare and life-threatening event of pregnancy for both the mother and the
      fetus. Obstetricians should be cautious about umbilical cord insertion and
      placental adherence abnormalities in pregnancies conceived by assisted
      reproductive technologies (ART) particularly in women with Mullerian anomalies. 

PMID- 24455352
TI  - A change of heart: case series of peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is an uncommon disease of pregnancy, occurring
      in about 1 in 2000 live births, and is characterized by the development of heart
      failure, due to left ventricular systolic dysfunction. It is associated with high
      rates of maternal and neonatal mortality. Cardiac disease is the leading cause of
      maternal death in the UK: PPCM accounts for about 17% of these. Clinical findings
      of decompensated heart failure (HF) are often masked by the normal physiological
      changes seen in pregnancy making the diagnosis challenging. A high index of
      suspicion is essential-prompting referral for echocardiogram, which is crucial
      for diagnosis. Favourable prognosis is dependent on the early initiation of HF
      medications. Although full recovery occurs in around half of cases, left
      ventricular systolic dysfunction persists in a significant proportion of patients
      with PPCM and the risk of recurrence in subsequent pregnancies is high. The
      pathophysiology of PPCM is under intense research. We present four patients with
      PPCM and a review of the literature. Owing to the diagnostic challenge of PPCM
      and decompensated HF in pregnant mothers and its high mortality rate without
      treatment, prompt investigation and referral are key to improving maternal
      survival. 

PMID- 24455353
TI  - Spontaneous rupture of uterine vein in twin pregnancy.
AB  - Objective. Aim of our study is to present a case of a twin pregnancy following
      invitro fertilization cycle complicated with hemoperitoneum at third trimester.
      Case. A 26-year-old nulliparous pregnant woman at 32 weeks of gestation with twin
      pregnancy following invitro fertilization cycle complained of abdominal pain.
      After 48 hours of admission, laparotomy was performed with indications of
      aggravated abdominal pain and decreased hemoglobin levels. Utero-ovarian vein
      branch rupture was detected on the right posterior side of uterus and bleeding
      was stopped by suturing the vein. Etiopathogenesis of the present case still
      remains unclear. Conclusion. Spontaneous rupture of the uterine vessels during
      pregnancy is a rare complication and may lead to maternal and fetal morbidity and
      mortality. Diagnosis and treatment are based on the clinical symptoms of acute
      abdominal pain and laboratory tests of hypovolemic shock signs. 

PMID- 24455354
TI  - Conservative treatment of uterine cervical adenocarcinoma in pregnancy.
AB  - Cancer of the cervix is the most common malignancy diagnosed during pregnancy,
      with an incidence of 1-10 cases per 10,000 pregnancies. The desire of patients to
      maintain pregnancy and subsequent fertility is a difficult target to be achieved
      and should be widely studied, since it depends on the stage of disease,
      gestational age at diagnosis, and the woman's desire to maintain pregnancy. We
      describe in this report the case of a pregnant woman with invasive cervical
      adenocarcinoma in stage IB1 (FIGO) initially treated with neoadjuvant
      chemotherapy, followed by radical surgery and cesarean section in the same
      surgical procedure. 

PMID- 24455355
TI  - Uroperitoneum after caesarean section.
AB  - Intraoperative injuries of the bladder and the attendant vesicouterine and
      vesicovaginal fistulas formation are reported as rare events, but the rapid
      increase in the number of caesarean sections has contributed to the emergence of
      these complications. Early recognition of these complications makes them much
      easier to deal with, while simple measures intraoperatively can ensure that these
      complications will not escape attention. We present our rare case of
      uroperitoneum after cesarean section, the way of diagnosis and treatment, and due
      to this incident we review in detail the existing literature on the topic. 

PMID- 24455356
TI  - Ultrasound prenatal diagnosis of inguinal scrotal hernia and contralateral
      hydrocele.
AB  - Fetal inguinal scrotal hernia is a rare condition resulting in an abnormal
      embryonic process of the tunica vaginalis. We report a case of ultrasound
      prenatal diagnosis of inguinal scrotal hernia associated with contralateral
      hydrocele in a woman at 37 weeks of gestation, referred to our clinic for a
      scrotal mass. Differential diagnosis includes hydrocele, teratoma, hemangiomas,
      solid tumours of testis, bowel herniation, and testicular torsion. Bowel
      peristalsis is an important ultrasound sign and it allowed us to make diagnosis
      of inguinal scrotal hernia. Diagnosis was confirmed at birth and a laparoscopic
      hernia repair was performed without complications on day 10. During surgery, a
      bilateral defect of canal inguinal was seen and considered as the cause of
      scrotal inguinal hernia and contralateral hydrocele observed in utero. 

PMID- 24455357
TI  - Thyroid metastasis from nonsmall cell lung cancer.
AB  - Background. Thyroid metastases are rare. Clinically, they represent less than 4%
      of thyroid malignancy in clinical studies. Aim. To assess various presentations
      and therapy for patients with lung cancer metastatic in the thyroid. Materials
      and Methods. We report a case of metastatic adenocarcinoma of the lung to the
      thyroid. We reviewed similar reports through PubmMed search from 1997 until 2013.
      Case Presentation. A 48-year-old lady was seen in the clinic for an
      adenocarcinoma of left upper lobe (LUL) of the lung; she received neoadjuvant
      chemotherapy then LUL lobectomy. After 9 months she presented with diffuse goiter
      initially believed to be a solitary metastatic lesion as it was positive for
      adenocarcinoma of lung origin on histopathological exam with TTF-1 positivity.
      Unfortunately, PET scan showed additional mediastinal lymphadenopathy.
      Conclusion. The treatment strategy for metastatic thyroid disease is based on a
      multidisciplinary approach, where thyroidectomy would have been considered in
      case of a solitary metastatic involvement, but further metastatic workup is
      mandated to direct further systemic therapy versus palliative radiation therapy. 

PMID- 24455358
TI  - A rare case of malignant glomus tumor of the esophagus.
AB  - Glomus tumors are rare neoplasms that usually occur on the hands in a subungual
      location, or sometimes in palms, wrists or soles of the feet. They are described
      as purple/pink tiny painful lesions with a triad of pain, local point tenderness,
      and cold hypersensitivity. They are almost always benign, but rare malignant
      variants have been reported. They have also been reported to be present at
      unusual locations, like the lung, stomach, or liver. Gastrointestinal glomus
      tumors are extremely rare tumors and very few cases have been reported in the
      literature. Most that have been reported were usually benign in nature. A rare
      esophageal glomangioma, mimicking a papilloma, was reported in 2006. We report a
      case of glomangiosarcoma (malignant glomus tumor) in a 49-year-old female, who
      presented with symptoms of dysphagia including some spasm and hoarseness and
      subjective unintentional weight loss. On endoscopic exam, she was found to have a
      distal esophageal mass with malignant features. Radiologically, the mass had a
      size of about 8 cm on the CT scan without evidence of metastases. Pathology and
      immunostaining of the biopsy showed features resembling a malignant glomus tumor.
      She underwent an endoscopic and laparoscopic staging of the tumor along with
      ultrasound. Based on the laparoscopic findings, which were consistent with the
      preoperative diagnosis, she was scheduled for an esophagectomy. Histopathology
      and immunophenotypic features of the excised mass were consistent with a
      diagnosis of malignant glomus tumor. 

PMID- 24455359
TI  - Cortical anaplastic ependymoma with significant desmoplasia: a case report and
      literature review.
AB  - Ectopic brain anaplastic ependymomas with no connection to the ventricles are
      rare. We present a rare case of a 25-year-old male who presented with generalized
      convulsions. Computed tomography (CT), Magnetic Resonance Imaging (MRI), and
      magnetic resonance spectroscopy (MRS) showed characters of an intra- and extra
      axial lesion. Intraoperatively, the lesion was a cortical solid mass that had no
      connections to the dura or to the ventricle. The histological diagnosis showed an
      anaplastic ependymoma with WHO grade III with distinctive desmoplasia. A
      literature review of ectopic anaplastic ependymomas regarding their clinical
      presentations, management, and prognostic factors was performed. There is a need
      to establish a clinically based histopathological grading system for anaplastic
      ependymomas. Ectopic anaplastic ependymomas should be included in the
      preoperative differential diagnosis. 

PMID- 24455360
TI  - Paraneoplastic mononeuritis multiplex as a presenting feature of adenocarcinoma
      of the lung.
AB  - Paraneoplastic neurologic syndromes are observed in less than 0.1% of cancer
      patients. Neurologic syndromes in lung cancer include Lambert-Eaton myasthenic
      syndrome, polyneuropathy, cerebellar degeneration, and rarely mononeuritis
      multiplex. In this case, a patient presenting with bilateral asymmetrical
      sensorimotor polyneuropathy who was diagnosed with adenocarcinoma of the lung is
      reported. 

PMID- 24455361
TI  - Primary breast leiomyosarcoma.
AB  - Primary leiomyosarcoma of the breast is an extremely rare neoplasm. Only few
      cases have been reported in the literature. We report here a case of breast
      leiomyosarcoma in a 44-years-old female and we discuss the data of the existing
      literature. 

PMID- 24455362
TI  - A new role of vemurafenib as a neoadjuvant treatment of axillary and brain
      melanoma metastases.
AB  - Vemurafenib is approved by the FDA for the management of unresectable or
      metastatic melanoma. However, its role as a neoadjuvant therapy has not been
      determined. We present the first documented case in which vemurafenib induced
      complete tumor necrosis of both lymph node and brain metastases within one month
      or less, an outcome that indicated that the patient was a good candidate for
      excisional surgery. 

PMID- 24455363
TI  - Waldenstrom's Macroglobulinemia and Peripheral Neuropathy, Organomegaly,
      Endocrinopathy, Monoclonal Gammopathy, and Skin Changes with a Bleeding Diathesis
      and Rash.
AB  - We report a case of a 29-year-old male who presented with paraesthesia and skin
      lesions with excessive bleeding after skin biopsy leading to hematology
      consultation. He was found to have prolonged partial thromboplastin time (PTT)
      and monoclonal gammopathy on serum protein electrophoresis (SPEP). He experienced
      excessive bleeding leading to hospitalization after bone marrow biopsy and
      required blood transfusion. He was diagnosed with Waldenstrom's Macroglobulinemia
      (WM), based on the presence of IgM- kappa type monoclonal (M) protein and
      infiltration of lymphoplasmacytic cells identified in bone marrow aspirates. He
      was noticed to have features of peripheral neuropathy, organomegaly,
      endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome). This is
      a very rare case of WM with POEMS syndrome which responded to chemotherapy using
      bortezomib, steroids, and rituximab. 

PMID- 24455364
TI  - Intravitreal and subtenon depot triamcinolone as treatment of retinitis
      pigmentosa associated cystoid macular edema.
AB  - We present a case of retinitis pigmentosa (RP) related cystoid macular edema
      (CME) refractory to oral acetazolamide and topical ketorolac that was treated
      with intravitreal and subtenon depot triamcinolone. A 32-year-old male with RP
      presented with complaints of bilateral decrease in visual acuity. His best
      corrected visual acuity (BCVA) was 20/50 in the right eye and 20/100 in the left
      eye. After being informed of the available treatment options, the patient
      received bilateral intravitreal injection triamcinolone. The patient's BCVA
      improved to 20/40 in the right eye and 20/50 in the left eye and the CME was
      resorbed. However, 5 months after the injection in the left eye and two months in
      the right eye, visual acuity decreased due to recurrence of CME. We performed a
      second intravitreal injection in the left eye with improvement of visual and
      anatomic results, but we observed a recurrence of CME. Afterwards, we treated the
      patient with subtenon depot triamcinolone in both eyes, with the result that
      there was no recurrence after 4 months in OD or after 3 months in OS. We conclude
      that intravitreal and subtenon depot triamcinolone appear to provide at least
      temporary benefit in refractory CME as regards the improvement of visual acuity. 

PMID- 24455365
TI  - A case of medication-resistant acanthamoeba keratitis treated by corneal
      crosslinking in Turkey.
AB  - Purpose. To report a case of medication-resistant acanthamoeba keratitis (AK)
      treated successfully by corneal crosslinking (CXL). Methods. A 26-year-old male
      with medication-resistant AK underwent a standard CXL procedure with local
      anesthesia, followed by central corneal epithelial debridement, application of
      riboflavin 0.1%, and UV-A irradiation. Results. The patient experienced a
      dramatic symptomatic improvement within 24 hours. At two months, keratitis was
      healed with a semitransparent paracentral scar that did not affect visual acuity.
      Conclusions. Our experience, considered in the context of recent studies,
      suggests that CXL may be an option for selected patients with medication
      resistant AK and corneal melting. CXL allows patients to avoid emergency
      keratoplasty and experience rapid symptomatic relief. 

PMID- 24455366
TI  - External Ophthalmomyiasis Caused by a Rare Infesting Larva, Sarcophaga
      argyrostoma.
AB  - Purpose. External ophthalmomyiasis (EO) is caused by infesting larvae belonging
      to various species of flies. Most documented cases result from sheep (Oestrus
      ovis) and Russian (Rhinoestrus purpureus) botfly larvae, but we recently
      discovered a rare case of EO caused by flesh fly (Sarcophaga argyrostoma) larvae.
      Here, we report the case of a patient with EO who had been hospitalized and
      sedated for 1 week because of unrelated pneumonia. Methods. Case report. Results.
      A total of 32 larvae were removed from the adnexae of both eyes. Larvae
      identification was confirmed through DNA analysis. Treatment with topical
      tobramycin resulted in complete resolution of EO. Conclusion. EO can be caused by
      S. argyrostoma, and the elderly and debilitated may require extra ocular
      protection against flies during sedation. 

PMID- 24455367
TI  - Arterial Injury to the Profunda Femoris Artery following Internal Fixation of a
      Neck of Femur Fracture with a Compression Hip Screw.
AB  - We report the case of an 82-year-old woman who developed extensive proximal thigh
      swelling and persistent anaemia following internal fixation of an extracapsular
      neck of femur fracture with a dynamic hip screw (DHS). This was revealed to be a
      pseudoaneurysm of a branch of profunda femoris artery on angiography. Her case
      was further complicated by a concurrent pulmonary embolism (PE). She underwent
      endovascular coil embolisation of the pseudoaneurysm. An IVC filter was inserted
      and the patient was fully anticoagulated once it had been ensured that there was
      no active bleeding. In this case, we review the potential for anatomical
      variations in the blood supply to this region and discuss treatment options for a
      complicated patient. We recommend that a pseudoaneurysm should be part of a
      differential diagnosis for postoperative patients with anaemia refractory to
      blood transfusion so as not to miss this rare but potentially serious
      complication. 

PMID- 24455368
TI  - Three Metachronous Osteosarcomas within 22 Years without Pulmonary Metastases: A
      Case Report and Review of the Literature.
AB  - Introduction. We present the extremely rare case of a patient with three
      metachronous osteosarcomas within 22 years without evident pulmonary
      manifestation of disease 30 years after first diagnosis. Case Presentation. In
      1983, a high-grade osteosarcoma of the left distal femur was diagnosed in an 18
      year-old Caucasian male. He received rotationplasty accompanied by pre- and
      postoperative chemotherapy. Ten years later, an osteoblastic osteosarcoma
      occurred in TH12. En bloc resection and pre- and postoperative chemotherapy
      followed. In 2005, the patient developed another high-grade osteosarcoma in his
      right distal femur. Treatment included a wide resection and reconstruction with a
      tumour endoprosthesis as well as (neo)adjuvant chemotherapy. After the third
      tumour occurrence, cytogenetic and molecular genetic examinations (p53, rb1) were
      performed, showing a normal genetic pattern. Screening for metastases never
      showed clinical evidence of extraskeletal tumour manifestation. Discussion. In
      patients presenting metachronous osteosarcoma, identification of their lesions
      clonality (second primary tumour or metastases) could lead to a better
      understanding of tumour development and help to filter patients who need extended
      long-term followup due to a higher risk of late occurring sarcoma recurrence. 

PMID- 24455369
TI  - Removal of a broken cannulated intramedullary nail: review of the literature and
      a case report of a new technique.
AB  - Nonunion of long bones fixed with nails may result in implant failure. Removal of
      a broken intramedullary nail may be a real challenge. Many methods have been
      described to allow for removal of the broken piece of the nail. In this paper, we
      are reviewing the different techniques to extract a broken nail, classifying them
      into different subsets, and describing a new technique that we used to remove a
      broken tibial nail with narrow canal. Eight different categories of implant
      removal methods were described, with different methods within each category. This
      classification is very comprehensive and was never described before. We described
      a new technique (hook captured in the medulla by flexible nail introduced from
      the locking hole) which is a valuable technique in cases of nail of a small
      diameter where other methods cannot be used because of the narrow canal of the
      nail. Our eight categories for broken nail removal methods simplify the concepts
      of nail removal and allow the surgeon to better plan for the removal procedure. 

PMID- 24455370
TI  - Locked superior dislocation of the acromioclavicular joint.
AB  - Acromioclavicular (AC) joint injuries account for approximately 3-5% of shoulder
      girdle injuries (Rockwood et al., 1998). Depending on severity of injury and
      direction of displacement these are classified using Rockwood classification
      system for AC joint dislocation. We present an unusual case presenting with
      locked superior dislocation of the AC joint highlighting the presentation and
      subsequent successful surgical management of such case. To our knowledge this has
      not been reported previously in literature. 

PMID- 24455371
TI  - A Newer Technique of Distal Ulna Reconstruction Using Proximal Fibula and TFCC
      Reconstruction Using Palmaris Longus Tendon following Wide Resection of Giant
      Cell Tumour of Distal Ulna.
AB  - Giant cell tumour of the bone (GCT) is a rare locally aggressive primary bone
      tumour with an incidence of 3% to 5% of all primary bone tumours. The most common
      location for this tumour is the long bone metaepiphysis especially of the distal
      femur, proximal tibia, distal radius, and the proximal humerus. Involvement of
      distal ulna is rare accounting for 0.45% to 3.2%. Considering local aggressive
      nature and high recurrence, wide resection is the treatment recommended.
      Instability of ulnar stump and ulnar translation of the carpals are known
      complications following resection of distal ulna. To overcome these problems, we
      attempted a newer technique of distal ulna reconstruction using proximal fibula
      and TFCC reconstruction using palmaris longus tendon following wide resection of
      giant cell tumour of distal ulna in a 44-year-old male. This technique of distal
      radioulnar joint reconstruction has excellent functional results with no evidence
      of recurrence after one-year followup. 

PMID- 24455372
TI  - Pneumomediastinum, subcutaneous emphysema, and tracheal tear in the early
      postoperative period of spinal surgery in a paraplegic achondroplastic dwarf.
AB  - Achondroplasia was first described in 1878 and is the most common form of human
      skeletal dysplasia. Spinal manifestations include thoracolumbar kyphosis, foramen
      magnum, and spinal stenosis. Progressive kyphosis can result in spinal cord
      compression and paraplegia due to the reduced size of spinal canal. The deficits
      are typically progressive, presenting as an insidious onset of paresthesia,
      followed by the inability to walk and then by urinary incontinence. Paraplegia
      can be the result of direct pressure on the cord by bone or the injury to the
      anterior spinal vessels by a protruding bone. Surgical treatment consists of
      posterior instrumentation, fusion with total wide laminectomy at stenosis levels,
      and anterior interbody support. Pedicle screws are preferred for spinal
      instrumentation because wires and hooks may induce spinal cord injury due to the
      narrow spinal canal. Pedicle lengths are significantly shorter, and 20-25 mm long
      screws are appropriate for lower thoracic and lumbar pedicles in adult
      achondroplastic There is no information about the appropriate length of screws
      for the upper thoracic pedicles. Tracheal injury due to inappropriate pedicle
      screw length is a rare complication. We report an extremely rare case of tracheal
      tear due to posterior instrumentation and its management in the early
      postoperative period. 

PMID- 24455373
TI  - Renal clear cell carcinoma and tonsil metastasis.
AB  - Renal cell carcinoma is the most common renal tumor in adults. Clear cell
      carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year
      old woman came to our department due to the appearance of massive hemoptysis and
      pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma
      treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated
      mass in the left tonsillar lodge and decided to subject the patient to an
      immediate tonsillectomy. Postoperative histology showed nests of cells with
      highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to
      make the diagnosis of renal clear cell carcinoma metastasis. Only few authors
      described metastasis of renal cell carcinoma in this specific site. 

PMID- 24455374
TI  - Cervical thymic cyst mimicking laryngocele.
AB  - Cervical thymic cysts are nearly 0.3% of all congenital cervical cysts. Thymic
      cysts are asymptomatic, but they rarely complain of dysphagia or tracheal
      obstruction symptoms. A soft, mobile, and painless mass increasing with valsalva
      maneuver directs the diagnosis of laryngocele. There has not been any study in
      the literature in which thymic cyst presenting like laryngocele. We hereby
      present a case of thymic cyst mimicking laryngocele that has not been reported so
      far. 

PMID- 24455375
TI  - Partial Recovery of Audiological, Vestibular, and Radiological Findings following
      Spontaneous Intralabyrinthine Haemorrhage.
AB  - The diagnosis, work-up, and treatment of sudden sensorineural hearing loss and
      sudden vestibular loss vary widely between units. With the increasing access to
      both magnetic resonance imaging and objective vestibular testing, our
      understanding of the various aetiologies at hand is increasing. Despite this, the
      therapeutic options are limited and without a particularly strong evidence base.
      We present a rare, yet increasingly diagnosed, case of intralabyrinthine
      haemorrhage (ILH) together with radiological, audiological, and vestibular test
      results. Of note, this occurred spontaneously and has shown partial recovery in
      all the mentioned modalities. 

PMID- 24455376
TI  - Follicular lymphoma in situ presenting as dermatopathic lymphadenopathy.
AB  - Introduction. Follicular lymphoma in situ (FLIS) is a recently described entity
      with few cases recognized worldwide. To our knowledge, this is the first FLIS
      reported from West Africa. Case Presentation. We present the case of a 48-year
      old civil servant with axillary lymphadenopathy discovered on routine
      mammography. On histology, a predominant reactive change with aggregates of
      melanophages was seen prompting a diagnosis of reactive lymphadenopathy.
      Immunohistochemistry done in our laboratory showed CD10 and Bcl-6 positive
      germinal centres with a small population of Bcl-2 positive germinal centre centre
      cells that were limited to some of the germinal centres. Conclusion. This
      highlights the use of immunohistochemistry in lymph node pathology-a resource
      which is very limited in our environment. 

PMID- 24455377
TI  - Clear cell adenocarcinoma of the renal pelvis in a male patient.
AB  - Carcinoma of the renal pelvis is an uncommon renal neoplasm. Clear cell
      adenocarcinoma in the urinary tract is rare and has a histomorphology resembling
      that of the female genital tract. We herein present a case of clear cell
      adenocarcinoma of the renal pelvis, which is the first example in a male patient
      to our knowledge. A 54-year-old man presented with right flank pain. The tumor
      was associated with renal stones and hydronephrosis and invaded into the
      peripelvic fat tissue with regional lymph node metastasis. The patient died of
      metastatic disease six months postoperatively. Histologically, the tumor showed
      complex papillary architecture lined with clear and hobnail cells. Clear cell
      adenocarcinoma of the renal pelvis may pose a diagnostic challenge on
      histological grounds, particularly in the distinction from renal cell carcinoma.
      The immunohistochemical stains could help confirm the diagnosis. Due to its
      rarity, an effective treatment regimen remains to be determined. 

PMID- 24455378
TI  - Serotonin syndrome after sertraline overdose in a child: a case report.
AB  - Serotonin syndrome is a potentially life-threatening drug effect. It may be
      misdiagnosed because it has mostly been reported in adults. Case Report. An 8
      year-old girl with behavioral problems and medicated with risperidone and
      sertraline was admitted in the emergency department after she had taken
      voluntarily 1500 mg of sertraline (50 mg/kg). At admission, she had marked
      agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had
      fever and periods of hypertension. She also showed generalized rigidity and
      involuntary movements. She was treated with fluids and iv diazepam, midazolam,
      clemastine, and biperiden. As the patient presented a severe insomnia and a
      progressive rhabdomyolysis, she was transferred to pediatric intensive care unit
      (ICU), where she was under treatment with cyproheptadine, mechanical ventilation,
      and muscular paralysis for 11 days. She was discharged from hospital a few days
      later with no neurological sequelae. Conclusions. Serotonin syndrome is still not
      well recognized by physicians. In our patient, the diagnosis was made early due
      to the history of overdose with serotonin reuptake inhibitors and the triad of
      mental, neurological, and autonomic signs. Parents must be educated to prevent
      children from having free access to drugs, avoiding self-medication or overdose. 

PMID- 24455379
TI  - Magnetic resonance cholangiopancreatography in the diagnosis of haemobilia.
AB  - Haemobilia is a rare cause of unrecognized gastrointestinal bleeding and is hard
      to diagnose. Through the present case report we aim to corroborate magnetic
      resonance relevance in the evaluation of biliary system and bile features,
      investigating on its role in patients with acute biliary diseases. We report a
      case of a Caucasian 48-year-old man who was admitted due to abdominal pain and
      fever. After an ultrasonography exam we detected multiple cysts in the hepatic
      left lobe: imaging features, laboratory findings, and patient past work
      experience (woodcutter) suggested a diagnosis of hepatic Echinococcosis. Once
      surgery decision was taken, patient underwent an intervention of
      cystopericystectomy. On the 8th postoperative day, the procedure was complicated
      by black stool, jaundice, and severe anaemia. Acomputed tomography revealed an
      inhomogeneous collection with some air bubbles in the area of previous surgical
      intervention, but it was not able to solve the diagnosis question. At this stage
      a magnetic resonance study was mandatory. On T2-weighted images we observed an
      expanse gallbladder with hypointense intraluminal material and a considerable
      intrahepatic biliary system dilatation due to bloody material. On the basis of
      these examination results, we supposed haemobilia arising from previous surgical
      intervention. A therapeutic endoscopic retrograde cholangiopancreatography
      procedure led to decompression of biliary system through a major papilla
      sphincterotomy with spillage of bile mixed with blood clots. 

PMID- 24455380
TI  - An asymptomatic large anterior sacral meningocele in a patient with a history of
      gestation: a case report with radiological findings.
AB  - Anterior sacral meningocele is characterized by herniation of the meningeal sac
      due to a developmental bone defect in the front of a sacrum bone. It was first
      described in 1837. The sacral meningocele may be congenital or acquired. It is
      usually discovered during a rectal or pelvic examination as a cystic lesion or
      discovered incidentally. Most of the symptoms are due to compression on the
      adjacent organs. In this paper, we present a case of an asymptomatic female
      patient who had a pelvic cyst detected during a routine obstetric ultrasound
      examination. We show radiological findings of the detailed postpartum evaluation
      of the cyst, which led to detection of sacral agenesis, huge anterior sacral
      meningocele, and significant arcuate uterus. 

PMID- 24455381
TI  - Spontaneous ureteral rupture diagnosis and treatment.
AB  - Rupture of the urinary collecting system associated with perinephric or
      retroperitoneal extravasation of the urine is an unusual condition and it is
      commonly associated with renal obstructing disease. Perforation could occur at
      any level from the calix to the bladder but it is usually seen at the fornices
      and upper ureter. It may lead to several serious consequences including urinoma,
      abscess formation, urosepsis, infection, and subsequent irreversible renal
      impairment. We report a case of a 69-year-old woman who presented at the
      emergency department of our institution with severe abdominal pain. Due to
      symptomatology worsening, complete laboratory evaluation was performed and the
      patient underwent abdominal contrast enhanced computed tomography (CT) evaluation
      which showed contrast agent extravasation outside the excretory system without
      any evidence of renal calculi at basal acquisition. It was decided to perform a
      double-J stent placement which was followed by complete healing of the ureter and
      its removal was performed 8 weeks later. Diagnosis and therapeutic approaches are
      discussed. 

PMID- 24455382
TI  - A unique case of relapsing polychondritis presenting with acute pericarditis.
AB  - Relapsing polychondritis (RP) is an inflammatory disease of the cartilaginous
      tissue primarily affecting the cartilaginous structures of the ear, nose, joints,
      and the respiratory system. Cardiovascular complications of RP are associated
      with high morbidity and mortality and occur most commonly as valvular disease.
      Pericarditis is a less common complication, occurring in 4% of patients with RP
      and has not previously been described at presentation. We describe a case of
      relapsing polychondritis with acute pericarditis at presentation. 

PMID- 24455383
TI  - Rheumatoid Arthritis and Familial Mediterranean Fever or Sacroiliitis Accompanied
      by FMF.
AB  - The coexistence of rheumatoid arthritis (RA) and familial Mediterranean fever
      (FMF) has been rarely seen in case reports in the literature. Herein, we wanted
      to present a patient who had been followed up and treated as RA, but on
      investigation we concluded that he really had FMF and its joint complaints
      associated with sacroiliitis. Recovery was achieved by etanercept administered as
      if he was an RA patient. 

PMID- 24455384
TI  - Successful Use of Higher-Dose Etanercept for Multirefractory Systemic Flare of
      Adult-Onset Still's Disease with Liver Failure with No Response to Tocilizumab
      Therapy.
AB  - A 21-year-old woman with refractory systemic flare of adult-onset Still's disease
      with liver failure despite high-dose corticosteroids, cyclosporine, tacrolimus,
      and tocilizumab, was successfully treated with additional use of etanercept.
      Etanercept at a dose of 50 mg weekly was partially effective but could not reduce
      the dose of concomitant betamethasone from 5 mg/day. Etanercept at a dose of 75
      mg weekly could lead her to clinical remission and enabled successful tapering
      off the corticosteroids and discontinuation of etanercept. Normalization of serum
      C-reactive protein and interleukin 6 and persistent elevation of serum tumor
      necrosis factor alpha under the treatment with high-dose corticosteroids and
      immunosuppressants suggest that tumor necrosis factor alpha was more deeply
      involved than at least interleukin 6 in the pathogenesis of refractoriness of the
      disease in this patient, and these findings might be indicative of potential
      efficacy for adjunctive use of a tumor necrosis factor inhibitor rather than an
      interleukin 6 inhibitor. 

PMID- 24455385
TI  - Delayed presentation of intussusception with perforation after splenectomy in
      patient with blunt abdominal trauma.
AB  - Adult intussusception (AI) following blunt abdominal trauma (BAT) is a rare
      surgical condition. We present a case of delayed diagnosis of ileocecal junction
      intussusception with a perforation of small bowel in a 34-year-old male with a
      history of fall from height. Initial exploratory laparotomy revealed shattered
      spleen requiring splenectomy. Initial abdominal computerized tomography scanning
      (CT) scan showed dilated small bowel with no organic obstruction. Patient started
      to improve with partial distention and was shifted to rehabilitation unit. On the
      next day, he experienced severe abdominal distention and vomiting. Abdominal CT
      showed characteristic intussusception at the distal ileum. Secondary exploratory
      laparotomy revealed severe adhesions of stomach and small bowel to the anterior
      abdominal wall with dilated small bowel loops and intussusception near the
      ileocecal junction with perforation of small bowel. The affected area was
      resected and side-to-side stapled anastomosis was performed. Though small bowel
      intussusception is a rare event, BAT patients with delayed symptoms of bowel
      obstruction should be carefully evaluated for missed intussusception. 

PMID- 24455386
TI  - Concomitant gastrointestinal stromal tumor of the stomach and gastric
      adenocarcinoma in a patient with billroth 2 resection.
AB  - Background. With this study we focus on the etiopathogenesis and on the therapy
      of the simultaneous occurrence of Gastric gastrointestinal stromal tumor (gGIST)
      and adenocarcinoma of the stomach in a patient with Billroth II gastric resection
      (BIIGR). We report the first case of this event and a review of the literature.
      Methods. A 70-year-old man with a BIIGR, affected by adenocarcinoma of the
      stomach, was successfully treated with total gastrectomy. The histological
      examination showed a gastric adenocarcinoma with a synchronous GIST sized 2 cm
      and S-100, CD117, and CD34 positive. The mutation of PDGFR gene was detected.
      Discussion. This tumor is a rare mesenchymal neoplasm of the gastrointestinal
      tract. Few cases of synchronous gastric adenocarcinoma and GIST are observed in
      the literature and no case in patients with BIIGR. Various hypotheses have been
      proposed to explain this occurrence. It is frequently attributed to
      Metallothioneins genes mutations or embryological abnormalities, but this has not
      been proven yet. We suggest a hypothesis about the etiopathogenesis of this event
      in a BIIGR patient. Conclusion. GIST may occur synchronously with gastric
      adenocarcinoma. This simultaneous occurrence needs more studies to be proven. The
      study of Cajal cells' proliferation signalling is crucial to demonstrate our
      hypotesis. 

PMID- 24455387
TI  - Complicated sporadic cardiac myxomas: a second recurrence and myxomatous cerebral
      aneurysms in one patient.
AB  - A second recurrence of an excised nonfamilial cardiac myxoma is rare. Myxomatous
      cerebral aneurysms as a complication of cardiac myxomas are equally rare. A
      unique case of a patient with a total of 4 myxomas over a 20-year interval is
      presented. Her most recent presentation was a second recurrence of a left atrial
      myxoma, a de novo right atrial myxoma, and multiple cerebral myxomatous
      aneurysms. The challenging reconstruction of the normal anatomy was achieved with
      the use of porcine extracellular matrix patches. A diagnostic cerebral angiogram
      was later performed, and the aneurysms will be monitored for growth and possible
      intervention. 

PMID- 24455388
TI  - Trauma as pathogenesis of a plantar forefoot fibrolipoma: first case and review
      of the literature.
AB  - Lipomas and their variants are benign soft-tissue tumors that occur at any age
      and most frequently on the upper back and neck, shoulder, and abdomen. The foot
      is a relatively uncommon site for soft-tissue neoplasia and the etiology is not
      usually related to trauma. We describe a case of a pedunculated fibrolipoma of
      the forefoot that originated from a cut wound at the Atlantic Ocean. A brief
      review of the literature is also given. 

PMID- 24455389
TI  - Intestinal Necrosis due to Giant Ovarian Cyst: A Case Report.
AB  - Intestinal pathologies due to ovarian cyst are observed rarely. Although a
      limited number of cases in neonatal and adolescent periods have been observed, no
      adult case has been reported in the literature. Two mechanisms are involved in
      intestinal complications due to ovarian cysts: torsion due to adhesion or
      compression of giant ovarian mass with a diameter of 9-10 cm. We report here a
      terminal ileum necrosis case due to compression by an ovarian cyst with 11 * 10 *
      7 cm size in an 81-year-old woman. 

PMID- 24455390
TI  - Removal of Eroded Gastric Bands Using a Transgastric SILS Device.
AB  - Background. Laparoscopic adjustable gastric banding (LAGB) is a popular method
      for the treatment of morbid obesity. One of the most feared complications is
      gastric band erosion which occurs with a reported incidence of 0.3 to 14%.
      Intragastric migrated bands are best managed by endoscopic removal. Recent case
      studies reported successful endoscopic removal of intragastric migrated bands,
      but it is not always possible. We report our first experience with a transgastric
      removal of eroded bands using a Single Incision Laparoscopic Surgery (SILS)
      device. Methods. A patient who underwent gastric banding in the past (2007)
      presented with symptoms of epigastric pain and weight gain. Preoperative
      gastroscopy revealed stomach wall erosion with the gastric band partially (2/3)
      migrated into the gastric lumen. Attempts to remove the band by endoscopy were
      not successful. A laparoscopy was performed and multiple adhesions with evidence
      of inflammation was seen in the upper abdomen around the band. A SILS port was
      inserted through a 2 cm incision in the left hypochondrium with the internal ring
      of the port placed into the stomach through a small anterior gastrotomy. The band
      was cut in the stomach and removed. The anterior gastrotomy was closed. We had a
      perfect intragastric view of the gastric banding. Results. There were no intra-
      or postoperative complications. The patient was discharged on the fifth
      postoperative day on a gastric adapted diet. Conclusion. Removal of a gastric
      band after gastric erosion by SILS is feasible, safe, and effective. This is the
      first reported case of transgastric removal of eroded bands using an SILS device.

PMID- 24455391
TI  - Superior mesenteric venous thrombosis after laparoscopic exploration for small
      bowel obstruction.
AB  - Mesenteric venous thrombosis is a rare cause of intestinal ischemia which is
      potentially life-threatening because it can lead to intestinal infarction.
      Mesenteric venous thrombosis rarely develops after abdominal surgery and is
      usually associated with coagulation disorders. Associated symptoms are generally
      subtle or nonspecific, often resulting in delayed diagnosis. A 68-year-old woman
      underwent laparoscopic exploration for small bowel obstruction, secondary to
      adhesions. During the procedure, an intestinal perforation was identified and
      repaired. Postoperatively, the abdominal pain persisted and repeat exploration
      was undertaken. At repeat exploration, a perforation was identified in the small
      bowel with a surrounding abscess. After the second operation, the abdominal pain
      improved but anorexia persisted. Contrast enhanced abdominal computed tomography
      was performed which revealed superior mesenteric venous thrombosis.
      Anticoagulation therapy with heparin was started immediately and the thrombus
      resolved over the next 6 days. Although rare, this complication must be
      considered in patients after abdominal surgery with unexplained abdominal
      symptoms. 

PMID- 24455392
TI  - Conservative management of major liver necrosis after angioembolization in a
      patient with blunt trauma.
AB  - Management of liver injury is challenging particularly for the advanced grades.
      Increased utility of nonoperative management strategies increases the risk of
      developing massive liver necrosis (MLN). We reported a case of a 19-year-old male
      who presented with a history of motor vehicle crash. Abdominal computerized
      tomography (CT) scan revealed large liver laceration (Grade 4) with blush and
      moderate free hemoperitoneum in 3 quadrants. Patient was managed nonoperatively
      by angioembolization. Two anomalies in hepatic arteries origin were reported and
      both vessels were selectively cannulated and bilateral gel foam embolization was
      achieved successfully. The patient developed MLN which was successfully treated
      conservatively. The follow-up CT showed progressive resolution of necrotic areas
      with fluid replacement and showed remarkable regeneration of liver tissues. We
      assume that patients with high-grade liver injuries could be managed successfully
      with a carefully designed protocol. Special attention should be given to the
      potential major associated complications. A tailored multidisciplinary approach
      to manage the subsequent complications would represent the best recommended
      strategy for favorable outcomes. 

PMID- 24455393
TI  - Arteriojejunal Fistula Presenting with Recurrent Obscure GI Hemorrhage in a
      Patient with a Failed Pancreas Allograft.
AB  - We present a case of a patient with a failed pancreaticoduodenal allograft with
      exocrine enteric-drainage who developed catastrophic gastrointestinal (GI)
      hemorrhage. Over the course of a week, she presented with recurrent GI bleeds of
      obscure etiology. Multiple esophago-gastro-duodenoscopic (EGD) and colonoscopic
      evaluations failed to reveal the source of the hemorrhage. A capsule endoscopy
      and a technetium-labeled red blood cells (RBC) imaging study were similarly
      unrevealing for source of bleeding. She subsequently developed hemorrhagic shock
      requiring emergent superior mesenteric arteriography. Run off images revealed an
      external iliac artery aneurysm with fistulization into the jejunum. Coiled
      embolization was attempted but abandoned because of hemodynamic instability.
      Deployment of a covered endovascular stent into the right external iliac artery
      over the fistula site resulted in immediate hemodynamic stabilization. A high
      index of suspicion for arterioenteric fistulae is needed for diagnosis of this
      uncommon but eminently treatable form of GI hemorrhage in this patient
      population. 

PMID- 24455394
TI  - Renal transplantation in secondary amyloidosis associated with tuberculosis.
AB  - Although end-stage renal disease (ESRD) related to AA amyloidosis nephropathy
      secondary to tuberculosis is most common in our country, there are limited data
      concerning patient and graft outcome after renal transplantation (RTx). To the
      best of our knowledge, this is the first report of RTx in ESRD patient with
      secondary amyloidosis due to tuberculosis from India. A 30-year-old female with
      past history of pulmonary tuberculosis 3 years back was admitted with complaint
      of gradually progressive pedal oedema and nausea for 3 months. Renal biopsy was
      suggestive of secondary renal amyloidosis with vascular involvement and chronic
      tubulointerstitial involvement. She was transplanted with kidney from her 28-year
      old brother with 3/6 human leukocyte antigen match. She had immediate good graft
      function without any perioperative complications (cardiovascular, infections,
      rejection and delayed graft function). She was discharged with serum creatinine
      of 0.8 mg/dL. Her last serum creatinine level was 0.9 mg/dL with cyclosporine
      level of 100 mg/dL at 9-month followup without any medical or surgical
      complication. The quality of life also improved after transplantation. With
      careful selection, ESRD patients with secondary amyloidosis due to tuberculosis
      are eligible for RTx with favorable outcome and improved quality of life. 

PMID- 24455395
TI  - Laparoscopic nephroureterectomy for adult patient with primary obstructive
      megaureter.
AB  - A 29-year-old female with a complaint of abdominal distension was referred to our
      hospital. She had a history of being treated for pyelonephritis three times. By
      computed tomography and retrograde pyelography, she was diagnosed with adult left
      primary megaureter. Her left renal function was severely deteriorated. She hoped
      for surgical intervention before becoming pregnant. Laparoscopic
      nephroureterectomy for megaureters seems to be difficult due to the large size.
      By sucking urine from an inserted ureteral catheter and setting trocar positions,
      we successfully performed laparoscopic nephroureterectomy for megaureter. 

PMID- 24455396
TI  - Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion: A
      Rare Case Report with Review of the Literature.
AB  - Introduction. The recently recognized renal cell carcinomas associated with
      Xp11.2 translocations are rare tumors predominantly reported in children.
      Chromosome Xp11.2 translocation results in gene fusion related to transcription
      factor E3 (TFE3) that plays an important role in proliferation and survival. Case
      Report. Herein, we present two cases of a TFE3 translocation-associated RCC in
      young female adults, one detected incidentally and the other one presenting with
      gross hematuria. Tumor is characterized by immunohistochemistry and a literature
      review with optimal treatment regimen is presented. Discussion. Xp11.2
      translocation RCCs in adult patients are associated with advanced stages, large
      tumors, and extracapsular disease and usually have an aggressive clinical course.
      Conclusion. In TFE3 RCC, the genetic background may not only contribute to
      tumorigenesis, but also determine the response to chemotherapy and targeted
      therapy. Therefore it is necessary to diagnose this tumor entity accurately.
      Because of the small number of TFE3 gene fusion-related renal tumors described in
      the literature, the exact biologic behavior and impact of current treatment
      modalities remain to be uncertain. 

PMID- 24455397
TI  - Anomalous left main coronary artery: case series of different courses and
      literature review.
AB  - Background. Congenital anomalies of the coronary arteries are a cause of sudden
      cardiac death. Of the known anatomic variants, anomalous origination of a
      coronary artery from an opposite sinus of Valsalva (ACAOS) remains the main focus
      of debate. Case Series. We present three cases, all presenting to our facility
      within one week's time, of patients with newly discovered anomalous origination
      of the left coronary artery from the right sinus of Valsalva (L-ACAOS). All
      patients underwent cardiac computed tomography for evaluation of coronary anatomy
      along with other forms of functional testing. Despite the high risk nature of two
      of the anomalies, the patients are being treated medically without recurrence of
      symptoms. Summary. After review of the literature, we have found that the risk of
      sudden cardiac death in patients with congenital coronary anomalies, even among
      variants considered the highest risk, may be overestimated. In addition, the
      exact prevalence of coronary anomalies in the general population is currently
      underestimated. A national coronary artery anomaly registry based on cardiac
      computed tomography and invasive coronary angiography data would be helpful in
      advancing our understanding of these cardiac peculiarities. The true prevalence
      of congenital coronary anomalies and overall risk of sudden cardiac death in this
      population are not well known. Surgical intervention remains the mainstay of
      therapy in certain patients though recent investigations into the pathophysiology
      of these abnormalities have shown that the risk of surgery may outweigh the
      minimal reduction in risk of sudden cardiac death. 

PMID- 24455398
TI  - Characteristics of Multidrug Resistant Shigella and Vibrio cholerae O1 Infections
      in Patients Treated at an Urban and a Rural Hospital in Bangladesh.
AB  - We determined the frequency of multidrug resistant (MDR) infections with Shigella
      spp. and Vibrio cholerae O1 at an urban (Dhaka) and rural (Matlab) hospital in
      Bangladesh. We also compared sociodemographic and clinical features of patients
      with MDR infections to those with antibiotic-susceptible infections at both
      sites. Analyses were conducted using surveillance data from the International
      Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), for the years 2000
      2012. Compared to patients with antibiotic-susceptible for Shigella infections,
      those in Dhaka with MDR shigellosis were more likely to experience diarrhea for
      >24 hours, while, in Matlab, they were more likely to stay inhospital >24 hours.
      For MDR shigellosis, Dhaka patients were more likely than those in Matlab to have
      dehydration, stool frequency >10/day, and diarrheal duration >24 hours. Patients
      with MDR Vibrio cholerae O1 infections in Dhaka were more likely than those in
      Matlab to experience dehydration and stool frequency >10/day. Thus, patients with
      MDR shigellosis and Vibrio cholerae O1 infection exhibited features suggesting
      more severe illness than those with antibiotic-susceptible infections. Moreover,
      Dhaka patients with MDR shigellosis and Vibrio cholerae O1 infections exhibited
      features indicating more severe illness than patients in Matlab. 

PMID- 24455399
TI  - Growth of Mycobacterium avium subsp. paratuberculosis, Escherichia coli, and
      Salmonella Enteritidis during Preparation and Storage of Yogurt.
AB  - The purpose of this study was to determine the viability of Mycobacterium avium
      subsp. paratuberculosis (MAP), Escherichia coli (E. coli), and Salmonella
      Enteritidis (S. Enteritidis) during preparation and refrigerated storage of
      yogurt. Three yogurts were prepared using pasteurized commercial milk. Each
      yogurt was artificially contaminated with (1) MAP, (2) E. coli + S. Enteritidis,
      and (3) MAP + E. coli + S. Enteritidis. Samples were taken during and after the
      fermentation process until day 20 after inoculation. MAP was not detected during
      their preparation and short-term storage but was recuperated after starting at
      180 min after inoculation storage. Live bacterial counts of E. coli, and S.
      Enteritidis increased during the first 24 hours, followed by a slight decrease
      towards the end of the study. In this study it was shown how MAP, E. coli, and S.
      Enteritidis resisted the acidic conditions generated during the preparation of
      yogurt and low storage temperatures. This work contributes to current knowledge
      regarding survival of MAP, E. coli, and S. Enteritidis during preparation and
      refrigerated storage of yogurt and emphasizes the need to improve hygiene
      measures to ensure the absence of these pathogenic microorganisms in dairy
      products. 

PMID- 24455400
TI  - Canola Cake as a Potential Substrate for Proteolytic Enzymes Production by a
      Selected Strain of Aspergillus oryzae: Selection of Process Conditions and
      Product Characterization.
AB  - Oil cakes have excellent nutritional value and offer considerable potential for
      use in biotechnological processes that employ solid-state fermentation (SSF) for
      the production of high value products. This work evaluates the feasibility of
      using canola cake as a substrate for protease production by a selected strain of
      Aspergillus oryzae cultivated under SSF. The influences of the following process
      parameters were considered: initial substrate moisture content, incubation
      temperature, inoculum size, and pH of the buffer used for protease extraction and
      activity analysis. Maximum protease activity was obtained after cultivating
      Aspergillus oryzae CCBP 001 at 20 degrees C, using an inoculum size of 10(7)
      spores/g in canola cake medium moistened with 40 mL of water to 100 g of cake.
      Cultivation and extraction under selected conditions increased protease activity
      5.8-fold, compared to the initial conditions. Zymogram analysis of the enzymatic
      extract showed that the protease molecular weights varied between 31 and 200 kDa.
      The concentrated protease extract induced clotting of casein in 5 min. The
      results demonstrate the potential application of canola cake for protease
      production under SSF and contribute to the technological advances needed to
      increase the efficiency of processes designed to add value to agroindustrial
      wastes. 

PMID- 24455401
TI  - Different neural responses to a moral valence decision task in unipolar and
      bipolar depression.
AB  - Objectives. Patients affected by bipolar disorder (BP) and major depressive
      disorder (UP) share the susceptibility to experience depression and differ in
      their susceptibility to mania, but clinical studies suggest that the biological
      substrates of the two disorders could influence the apparently similar depressive
      phases. The few brain imaging studies available described different brain
      metabolic and neural correlates of UP and BP. Methods. We studied the BOLD neural
      response to a moral valence decision task targeting the depressive biases in
      information processing in 36 subjects (14 BP, 11 UP, and 11 controls). Results.
      Main differences between UP and controls and between UP and BP were detected in
      left ventrolateral prefrontal cortex (PFC, BA 47). Neural responses of BP
      patients differed from those of control subjects in multiple brain areas,
      including anterior cingulate cortex (ACC) and medial PFC, bilateral dorsolateral
      PFC, temporal cortex and insula, and parietal and occipital cortex. Conclusions.
      Our results are in agreement with hypotheses of dysfunctions in corticolimbic
      circuitries regulating affects and emotions in mood disorders and suggest that
      specific abnormalities, particularly in ventrolateral PFC, are not the same in UP
      and BP depression. 

PMID- 24455402
TI  - Plasma Fatty Acid binding protein 4 and risk of sudden cardiac death in older
      adults.
AB  - Although fatty acid binding protein 4 (FABP4) may increase risk of diabetes and
      exert negative cardiac inotropy, it is unknown whether plasma concentrations of
      FABP4 are associated with incidence of sudden cardiac death (SCD). We
      prospectively analyzed data on 4,560 participants of the Cardiovascular Health
      Study. FABP4 was measured at baseline using ELISA, and SCD events were
      adjudicated through review of medical records. We used Cox proportional hazards
      to estimate effect measures. During a median followup of 11.8 years, 146 SCD
      cases occurred. In a multivariable model adjusting for demographic, lifestyle,
      and metabolic factors, relative risk of SCD associated with each higher standard
      deviation (SD) of plasma FABP4 was 1.15 (95% CI: 0.95-1.38), P = 0.15. In a
      secondary analysis stratified by prevalent diabetes status, FABP4 was associated
      with higher risk of SCD in nondiabetic participants, (RR per SD higher FABP4:
      1.33 (95% CI: 1.07-1.65), P = 0.009) but not in diabetic participants (RR per SD
      higher FABP4: 0.88 (95% CI: 0.62-1.27), P = 0.50), P for diabetes-FABP4
      interaction 0.049. In summary, a single measure of plasma FABP4 obtained later in
      life was not associated with the risk of SCD in older adults overall.
      Confirmation of our post-hoc results in nondiabetic people in other studies is
      warranted. 

PMID- 24455403
TI  - The association of sleep disordered breathing with heart failure and other
      cardiovascular conditions.
AB  - An abundance of evidence exists in support of primary and secondary prevention
      for tackling the scourge of cardiovascular disease. Despite our wealth of
      knowledge, certain deficiencies still remain. One such example is the association
      between sleep disordered breathing (SDB) and cardiovascular disease. A clear body
      of evidence exists to link these two disease entities (independent of other
      factors such as obesity and smoking), yet our awareness of this association and
      its clinical implication does not match that of other established cardiovascular
      risk factors. Here, we outline the available evidence linking SDB and
      cardiovascular disease as well as discussing the potential consequences and
      management in the cardiovascular disease population. 

PMID- 24455404
TI  - Effects of dietary nitrates on systemic and cerebrovascular hemodynamics.
AB  - Cerebral blood flow dysregulation is often associated with hypertension. We
      hypothesized that a beetroot juice (BRJ) treatment could decrease blood pressure
      and cerebrovascular resistance (CVR). We subjected 12 healthy females to control
      and BRJ treatments. Cerebrovascular resistance index (CVRI), systolic blood
      pressure (SBP), total vascular resistance (TVR), and the heart rate-systolic
      pressure product (RPP) measured at rest and at two exercise workloads were lower
      after the BRJ treatment. CVRI, SBP, and RPP were lower without a lower TVR at the
      highest exercise level. These findings suggest improved systemic and cerebral
      hemodynamics that could translate into a dietary treatment for hypertension. 

PMID- 24455405
TI  - KIF6 719Arg Carrier Status Association with Homocysteine and C-Reactive Protein
      in Amnestic Mild Cognitive Impairment and Alzheimer's Disease Patients.
AB  - Recent research has demonstrated associations between statin use, KIF6 719Arg
      carrier status, and cholesterol levels and amnestic mild cognitive impairment
      (aMCI) and Alzheimer's disease (AD) patients. The association between 719Arg
      carrier status with homocysteine (tHcy) and c-reactive protein (CRP) levels in
      aMCI and AD has not been previously investigated. Data from 175 aMCI and AD
      patients were used for the analysis. 719Arg carriers had significantly lower
      levels of tHcy than noncarriers (P = 0.02). No significant difference in CRP
      levels between 719Arg carriers and noncarriers was present (P = 0.37). Logistic
      regression yielded no significant effect for 719Arg status on CRP [OR = 1.79
      (0.85, 3.83), P = 0.13] but did demonstrate a significant effect for tHcy [OR =
      0.44 (0.23, 0.83), P = 0.01] after adjusting for ApoE epsilon4 carrier status,
      age, gender, and statin use. This study is the first to explore the relationship
      between KIF6 719Arg carrier status with tHcy and CRP levels. 719Arg carriers were
      more likely to have normal tHcy levels after adjusting for ApoE epsilon4 status,
      age, gender, and statin use. These results suggest that the KIF6 gene might
      influence cardiovascular pathways associated with AD. 

PMID- 24455406
TI  - Copper status in Alzheimer's disease and other neurodegenerative disorders 2013.

PMID- 24455407
TI  - Modeling extinction risk of endemic birds of mainland china.
AB  - The extinction risk of endemic birds of mainland China was modeled over
      evolutionary time. Results showed that extinction risk of endemic birds in
      mainland China always tended to be similar within subclades over the evolutionary
      time of species divergence, and the overall evolution of extinction risk of
      species presented a conservatism pattern, as evidenced by the disparity-through
      time plot. A constant-rate evolutionary model was the best one to quantify the
      evolution of extinction risk of endemic birds of mainland China. Thus, there was
      no rate shifting pattern for the evolution of extinction risk of Chinese endemic
      birds over time. In a summary, extinction risk of endemic birds of mainland China
      is systematically quantified under the evolutionary framework in the present
      work. 

PMID- 24455408
TI  - Conservation/Mutation in the splice sites of cytokine receptor genes of mouse and
      human.
AB  - Conservation/mutation in the intronic initial and terminal hexanucleotides was
      studied in 26 orthologous cytokine receptor genes of Mouse and Human. Introns
      began and ended with the canonical dinucleotides GT and AG, respectively.
      Identical configurations were found in 57% of the 5' hexanucleotides and 28% of
      the 3' hexanucleotides. The actual conservation percentages of the individual
      variable nucleotides at each position in the hexanucleotides were determined, and
      the theoretical rates of conservation of groups of three nucleotides were
      calculated under the hypothesis of a mutual evolutionary independence of the
      neighboring nucleotides (random association). Analysis of the actual conservation
      of groups of variable nucleotides showed that, at 5', GTGAGx was significantly
      more expressed and GTAAGx was significantly less expressed, as compared to the
      random association. At 3', TTTxAG and xTGCAG were overexpressed as compared to a
      random association. Study of Mouse and Human transcript variants involving the
      splice sites showed that most variants were not inherited from the common
      ancestor but emerged during the process of speciation. In some variants the
      silencing of a terminal hexanucleotide determined skipping of the downstream
      exon; in other variants the constitutive splicing hexanucleotide was replaced by
      another potential, in-frame, splicing hexanucleotide, leading to alterations of
      exon lengths. 

PMID- 24455409
TI  - Indian craniometric variability and affinities.
AB  - Recently published craniometric and genetic studies indicate a predominantly
      indigenous ancestry of Indian populations. We address this issue with a fuller
      coverage of Indian craniometrics than any done before. We analyse metrical
      variability within Indian series, Indians' sexual dimorphism, differences between
      northern and southern Indians, index-based differences of Indian males from other
      series, and Indians' multivariate affinities. The relationship between a
      variable's magnitude and its variability is log-linear. This relationship is
      strengthened by excluding cranial fractions and series with a sample size less
      than 30. Male crania are typically larger than female crania, but there are also
      shape differences. Northern Indians differ from southern Indians in various
      features including narrower orbits and less pronounced medial protrusion of the
      orbits. Indians resemble Veddas in having small crania and similar cranial shape.
      Indians' wider geographic affinities lie with "Caucasoid" populations to the
      northwest, particularly affecting northern Indians. The latter finding is
      confirmed from shape-based Mahalanobis-D distances calculated for the best
      sampled male and female series. Demonstration of a distinctive South Asian
      craniometric profile and the intermediate status of northern Indians between
      southern Indians and populations northwest of India confirm the predominantly
      indigenous ancestry of northern and especially southern Indians. 

PMID- 24455410
TI  - Necrotizing Soft Tissue Infections: Surgeon's Prospective.
AB  - Necrotizing soft tissue infections (NSTIs) are fulminant infections of any layer
      of the soft tissue compartment associated with widespread necrosis and systemic
      toxicity. Delay in diagnosing and treating these infections increases the risk of
      mortality. Early and aggressive surgical debridement with support for the failing
      organs significantly improves the survival. Although there are different forms of
      NSTIs like Fournier's gangrene or clostridial myonecrosis, the most important
      fact is that they share common pathophysiology and principles of treatment. The
      current paper summarizes the pathophysiology, clinical features, the diagnostic
      workup required and the treatment principles to manage these cases. 

PMID- 24455411
TI  - Decayed, Missing, and Filled Teeth Index and Periodontal Health in Osteoporotic
      Patients Affected by BRONJ: An Observational Study.
AB  - The aim of this paper is to describe the incidence of decayed, missing, and
      filled teeth (DMFT) and periodontal disease in 32 osteoporotic patients affected
      by bisphosphonate-related osteonecrosis of the jaw (BRONJ). Moreover, an
      investigation between the obtained data and 20 patients treated with
      bisphosphonate drugs and with no evidence of ONJ has been performed.
      Osteonecrosis of the jaws is a rare complication in a subset of patients
      receiving bisphosphonate drugs. Based on a growing number of case reports and
      institutional reviews, this kind of therapy can cause exposed and necrotic bone
      specifically in the jawbones. From April 2009 to June 2012, 32 osteoporotic
      patients treated with oral or intravenous (I.V.) bisphosphonates have been
      recorded. The patients' oral health has been compared with 20 bisphosphonates
      patients with no ONJ. The incidence of decayed, missing, and filled teeth (DMFT)
      and periodontal disease was recorded in all patients and student's t-test was
      applied for comparing the two investigated groups data. Data demonstrated how the
      poor dental hygiene and periodontal disease of the BRONJ patients' are connected
      with the occurrence of jawbone necrosis. 

PMID- 24455412
TI  - Adherence and persistence with once-daily teriparatide in Japan: a retrospective,
      prescription database, cohort study.
AB  - Adherence and persistence with osteoporosis treatments are essential for reducing
      fracture risk. Once-daily teriparatide is available in Japan for treating
      osteoporosis in patients with a high risk of fracture. The study objective was to
      describe real-world adherence and persistence with once-daily teriparatide 20 MUg
      during the first year of treatment for patients who started treatment during the
      first eight months of availability in Japan. This prescription database study
      involved patients with an index date (first claim) between October 2010 and May
      2011, a preindex period >=6 months, and a postindex period >=12 months and who
      were aged >45 years. Adherence (medication possession ratio (MPR)) and
      persistence (time from the start of treatment to discontinuation; a 60-day gap in
      supply) were calculated. A total of 287 patients started treatment during the
      specified time period; 123 (42.9%) were eligible for inclusion. Overall mean
      (standard deviation) adherence was 0.702 (0.366), with 61.0% of patients having
      high adherence (MPR > 0.8). The percentage of patients remaining on treatment was
      65.9% at 180 days and 61.0% at 365 days. Our findings suggest that real-world
      adherence and persistence with once-daily teriparatide in Japan are similar to
      that with once-daily teriparatide in other countries and with other osteoporosis
      medications. 

PMID- 24455413
TI  - Thyroid Lobectomy Is Associated with Excellent Clinical Outcomes in Properly
      Selected Differentiated Thyroid Cancer Patients with Primary Tumors Greater Than
      1 cm.
AB  - Background and Objective. An individualized risk-based approach to the treatment
      of thyroid cancer is being extensively discussed in the recent literature.
      However, controversies about the ideal surgical approach remain an important
      issue with regard to the impact on prognosis and follow-up strategies. This study
      was designed to describe clinical outcomes in a cohort of low and intermediate
      risk thyroid cancer patients treated with thyroid lobectomy. Methods.
      Retrospective review of 70 patients who underwent lobectomy. Results. After a
      median follow-up of 11 years, 5 patients (5/70, 7.1%) recurred and 5 had a
      completion for benign lesions, while 60 patients (86%) continued to be observed
      without evidence for disease recurrence. Suspicious ultrasound findings were
      significantly more common in patients that had structural disease recurrence
      (100% versus 4.3%, P < 0.001). Furthermore, a rising suppressed Tg value over
      time was also associated with structural disease recurrence (80% versus 21.5%, P
      = 0.01). After additional therapy, 99% of the patients had no evidence of
      disease. Conclusions. Properly selected thyroid cancer patients can be treated
      with lobectomy with excellent clinical outcomes. 

PMID- 24455415
TI  - Prevalence of malaria from blood smears examination: a seven-year retrospective
      study from metema hospital, northwest ethiopia.
AB  - Background. Malaria is a major public health problem in Ethiopia where an
      estimated 68% of the population lives in malarious areas. Studying its prevalence
      is necessary to implement effective control measures. Therefore, the aim of this
      study was to determine seven-year slide positive rate of malaria. Methods. A
      retrospective study was conducted at Metema Hospital from September 2006 to
      August 2012. Seven-year malaria cases data had been collected from laboratory
      registration book. Results. A total of 55,833 patients were examined for malaria;
      of these, 9486 (17%) study subjects were positive for malaria. The predominant
      Plasmodium species detected was P. falciparum (8602) (90.7%) followed by P. vivax
      (852) (9%). A slide positive rate of malaria within the last seven years (2006
      2012) was almost constant with slight fluctuation. The age groups of 5-14 years
      old were highly affected by malariainfection (1375) (20.1%), followed by 15-29
      years old (3986) (18.5%). High slide positive rate of malaria occurred during
      spring (September-November), followed by summer (June-August). Conclusion. Slide
      positive rate of malaria was high in study area. Therefore, health planners and
      administrators should give intensive health education for the community. 

PMID- 24455414
TI  - Amodiaquine-Artesunate versus Artemether-Lumefantrine against Uncomplicated
      Malaria in Children Less Than 14 Years in Ngaoundere, North Cameroon: Efficacy,
      Safety, and Baseline Drug Resistant Mutations in pfcrt, pfmdr1, and pfdhfr Genes.
AB  - Background. In Cameroon, both Artesunate-amodiaquine (AS/AQ) and artemether
      lumefantrine (AL) are used as first-line treatment against uncomplicated malaria
      in line with the WHO recommendations. We compared the efficacy and safety of both
      therapeutic combinations and determined the prevalence of drug resistance
      conferring mutations in three parasite genes. Methods. One hundred and fifty
      acute malaria patients between six months and 14 years of age were randomized to
      receive standard doses of either AS/AQ (73) or AL (77) and followedup for 28
      days. Outcome of treatment was according to the standard WHO classification. DNA
      samples from pretreatment parasite isolates were used to determine the prevalence
      of resistant mutations in the pfcrt, pfmdr1, and dhfr genes. Results. Both drug
      combinations induced rapid clearance of parasites and malaria symptoms. PCR
      corrected cure rates were 100% and 96.4% for AL. The combinations were well
      tolerated. Major haplotypes included CVIET (71%), CVMNT (25%) for the pfcrt; SND
      (100%) for the pfmdr1; IRN (79, 8%), NCS (8.8%), and mixed haplotype (11, 8%) for
      the dhfr. Conclusion. Both AS/AQ and AL were highly effective and well tolerated
      for the treatment of uncomplicated falciparum malaria in Ngaoundere, Cameroon.
      High prevalence of mutant pfcrt alleles confirms earlier observations. Long-term
      monitoring of safety and efficacy and molecular markers is highly solicited. 

PMID- 24455416
TI  - Restless legs syndrome and its associated risk factors in Parkinson's disease.
AB  - Introduction. Restless legs syndrome has been shown to negatively impact the
      quality of life of patients. Studies have shown an association between restless
      legs syndrome and Parkinson's disease. We attempted to investigate the prevalence
      of restless legs syndrome in Parkinson's disease patients and to identify
      associated risk factors. Method. This was a cross-sectional study among patients
      with idiopathic Parkinson's disease. Exclusion criterion was a Mini Mental State
      Examination score of less than 21/30. The International Restless Legs Syndrome
      Study Group criterion was used to identify patients with restless legs syndrome.
      Results. A total of 113 patients were recruited. The prevalence rate of restless
      legs syndrome in our cohort was 9.7% and was significantly associated with a
      younger onset of Parkinson's disease (P = 0.023), male gender (P = 0.045), higher
      Mini Mental State Examination score (P = 0.004), and less advanced Hoehn & Yahr
      stage (P = 0.014). Conclusion. The prevalence rate of restless legs syndrome in
      our Parkinson's disease population is in keeping with other studies published
      worldwide. The significance of the association between a younger onset of
      Parkinson's disease and restless legs syndrome needs to be further investigated. 

PMID- 24455417
TI  - Specimens from biopsies of colorectal polyps often harbor additional diagnoses.
AB  - Objectives. The utility of examining specimens from colorectal biopsies of polyps
      for nonneoplastic diseases is currently unknown. Our objectives were to
      characterize such additional diagnoses that could be rendered. Methods. We
      retrospectively and prospectively reviewed specimens from endoscopic biopsies of
      colorectal polyps obtained during routine screening or surveillance. Results. 17
      of 168 specimens (10.1%) contained additional diagnoses, including
      schistosomiasis, eosinophilic colitis, intestinal spirochetosis, melanosis coli,
      and other entities. These findings were easily overlooked because they often
      affected mucosa that was spared by the polyps or were often evident only at high
      magnification. Schistosomiasis, eosinophilic colitis, and intestinal
      spirochetosis were clinically occult. Conclusions. Specimens from biopsies of
      colorectal polyps often harbor other diagnoses, in addition to polyps, and can be
      simultaneously screened for polyps and examined for nonneoplastic diseases.
      Detection of other diagnoses in addition to polyps requires awareness,
      examination at high magnification, and examination of areas spared by the polyps.

PMID- 24455419
TI  - Cytological and Pathological Correlation of FNAC in Assessing Breast Lumps and
      Axillary Lymph Node Swellings in a Public Sector Hospital in India.
AB  - Background. Breast lumps have varied pathology, and there are different
      techniques to prove the diagnosis. The aim of the present study is to analyze the
      role of fine needle aspiration cytology (FNAC) of the breast lesions at our
      center. Methods. We had retrospectively analysed 854 patients who underwent FNAC
      for primary breast lumps and 190 patients who underwent FNAC for an axillary
      lymph node in the year 2010. Results. Of 854 patients, histological correlation
      was available in 723 patients. The analysis was done for 812 patients as medical
      records were not available for 42 patients. FNAC was false negative in seven
      cases; 2 cases of phyllodes were reported as fibroadenoma, and 5 cases of
      carcinoma were diagnosed as atypical hyperplasia. The sensitivity, specificity,
      and false negative value of FNAC in diagnosing breast lumps were 99% (715/723),
      100%, and 1%, respectively. Of 190 patients for whom FNAC was performed for
      axilla, 170 had proven to have axillary lymph node metastases, and the rest had
      reactive hyperplasia or inflammatory cells. Conclusions. FNAC is rapid, accurate,
      outpatient based, and less complicated procedure and helps in diagnosis of breast
      cancer, benign diseases, and axillary involvement in experienced hands with less
      chance of false results. 

PMID- 24455418
TI  - Evidences suggesting involvement of viruses in oral squamous cell carcinoma.
AB  - Oral cancer is one of the most common cancers and it constitutes a major health
      problem particularly in developing countries. Oral squamous cell carcinoma (OSCC)
      represents the most frequent of all oral neoplasms. Several risk factors have
      been well characterized to be associated with OSCC with substantial evidences.
      The etiology of OSCC is complex and involves many factors. The most clearly
      defined potential factors are smoking and alcohol, which substantially increase
      the risk of OSCC. However, despite this clear association, a substantial
      proportion of patients develop OSCC without exposure to them, emphasizing the
      role of other risk factors such as genetic susceptibility and oncogenic viruses.
      Some viruses are strongly associated with OSCC while the association of others is
      less frequent and may depend on cofactors for their carcinogenic effects.
      Therefore, the exact role of viruses must be evaluated with care in order to
      improve the diagnosis and treatment of OSCC. Although a viral association within
      a subset of OSCC has been shown, the molecular and histopathological
      characteristics of these tumors have yet to be clearly defined. 

PMID- 24455421
TI  - Low serum levels of myeloid progenitor inhibitory factor-1 predict good response
      to methotrexate in rheumatoid arthritis.
AB  - Background. Although the benchmark in the treatment of rheumatoid arthritis
      remains methotrexate, only 70% of patients respond. Thus, there is a need for
      predictive biomarkers. This study planned to evaluate serum levels of myeloid
      progenitor inhibitory factor-1 (MPIF-1) and monocyte chemoattractant protein 2
      (MCP-2)-as biomarkers. Methods. Patients with rheumatoid arthritis (RA) having
      high disease activity (DAS28-3v >= 5.1) were treated with oral methotrexate (MTX)
      for 12 weeks. Disease activity was measured by DAS28-3v (Modified Disease
      Activity Score 3 variables). Serum samples were stored at baseline and 12 weeks.
      Results. This study included 46 patients (F : M = 35 : 11) having mean (+/-SD)
      age of 42.6 +/- 11.3 yrs, disease duration of 4.7 +/- 4.5 yrs, and DAS28-3v of
      6.1 +/- 0.8. Serum MPIF1 was elevated in patients compared to controls (1636.7 +/
      1009.7, 441.2 +/- 173.8 pg/mL, P < 0.001), but there was no difference in MCP2
      levels (31.4 +/- 11.9, 33.8 +/- 24.0 pg/mL). Baseline MPIF-1 level was lower in
      good responders (DeltaDAS28-3v >= 1.2, N = 9) compared to poor responders
      (DeltaDAS28-3v < 0.6, N = 27) (1171.0 +/- 670.8, 1816.7 +/- 1154.1 pg/mL, P =
      0.05). On ROC analysis, baseline MPIF1 performed reasonably to predict good
      response; that is, DeltaDAS28-3v >= 1.2 (AUC 0.68, 95% CI 0.50-0.87).
      Conclusions. Lower baseline MPIF1 level predicted a good response to methotrexate
      at 12 weeks. 

PMID- 24455420
TI  - Adipose tissue in obesity-related inflammation and insulin resistance: cells,
      cytokines, and chemokines.
AB  - Adipose tissue is a complex organ that comprises a wide range of cell types with
      diverse energy storage, metabolic regulation, and neuroendocrine and immune
      functions. Because it contains various immune cells, either adaptive (B and T
      lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more
      recently identified, myeloid-derived suppressor cells), the adipose tissue is now
      considered as a bona fide immune organ, at the cross-road between metabolism and
      immunity. Adipose tissue disorders, such as those encountered in obesity and
      lipodystrophy, cause alterations to adipose tissue distribution and function with
      broad effects on cytokine, chemokine, and hormone expression, on lipid storage,
      and on the composition of adipose-resident immune cell populations. The resulting
      changes appear to induce profound consequences for basal systemic inflammation
      and insulin sensitivity. The purpose of this review is to synthesize the current
      literature on adipose cell composition remodeling in obesity, which shows how
      adipose-resident immune cells regulate inflammation and insulin resistance
      notably through cytokine and chemokine secretion-and highlights major research
      questions in the field. 

PMID- 24455422
TI  - Potential Protection of Coeloglossum viride var. Bracteatum Extract against
      Oxidative Stress in Rat Cortical Neurons.
AB  - The present study explored the neuroprotective effect of Coeloglossum viride var.
      bracteatum extract (CE) against oxidative stress in rat cortical neurons. The
      results demonstrated that administration of CE inhibited hydrogen peroxide
      induced neurotoxicity tested by MTT, LDH release, and TUNEL assays. We further
      found that CE inhibited the activation of caspase-3 (Csp3) induced by hydrogen
      peroxide. Moreover, CE was found to reverse the hydrogen peroxide-induced
      downregulation of active AKT and Bcl-2. We then showed that the neuroprotective
      effect of CE was blocked by adding the AKT inhibitor, Ly294002. Thus, our data
      strongly indicated that CE played a neuroprotective role against oxidative stress
      induced neurotoxicity. 

PMID- 24455423
TI  - Electrochemical analysis of antichemotherapeutic drug zanosar in pharmaceutical
      and biological samples by differential pulse polarography.
AB  - The electrochemical reduction of zanosar was investigated systematically by
      direct current polarography, cyclic voltammetry, and differential pulse
      polarography (DPP). A simple DPP technique was proposed for the direct
      quantitative determination of anticancer drug zanosar in pharmaceutical
      formulation and spiked human urine samples for the first time. The reduction
      potential was -0.28 V versus Ag/AgCl with a hanging mercury drop electrode in
      Britton-Robinson buffer as supporting electrolyte. The dependence of the
      intensities of currents and potentials on pH, concentration, scan rate,
      deposition time, and nature of the supporting electrolyte was investigated. The
      calibration curve was found to be linear with the following equation: y = 0.4041x
      + 0.012, with a correlation coefficient of 0.992 (R (2)) over a concentration
      range from 1.0 * 10(-7) M to 1.0 * 10(-3) M. In the present investigation, the
      achieved limit of detection (LOD) and limit of quantization (LQD) were 7.42 * 10(
      8) M and 2.47 * 10(-8) M; respectively. Excipients did not interfere with the
      determination of zanosar in pharmaceutical formulation and spiked urine samples.
      Precision and accuracy of the developed method were checked by recovery studies
      in pharmaceutical formulation and spiked human urine samples. 

PMID- 24455424
TI  - LC-NMR Technique in the Analysis of Phytosterols in Natural Extracts.
AB  - The ability of LC-NMR to detect simultaneously free and conjugated phytosterols
      in natural extracts was tested. The advantages and disadvantages of a gradient
      HPLC-NMR method were compared to the fast composition screening using SEC-NMR
      method. Fractions of free and conjugated phytosterols were isolated and analyzed
      by isocratic HPLC-NMR methods. The results of qualitative and quantitative
      analyses were in a good agreement with the literature data. 

PMID- 24455425
TI  - Simultaneous Adsorption and Degradation of Cr(VI) and Cd(II) Ions from Aqueous
      Solution by Silica-Coated Fe (0) Nanoparticles.
AB  - Core-shell silica-coated Fe(0) nanoparticles (Fe@SiO2) were prepared in one-step
      synthesis by aqueous reduction combined with modified Stober method. The as
      prepared Fe@SiO2 were then used for simultaneous removal of Cr(VI) and Cd(II)
      from aqueous solution. Batch tests indicated that Fe@SiO2 exhibited high removal
      capacity toward Cr(VI) and Cd(II). Cr(VI) was removed by Fe@SiO2 through
      reduction rather than adsorption, while Cd(II) removal was mainly through
      adsorption. The removal rate increased with increasing initial Fe NPs dose and
      decreased with increasing initial Cr(VI) and Cd(II) concentrations. Cd(II)
      adsorption was also strengthened by Cr(VI) reduction with the release of OH(-).
      The removals of Cr(VI) and Cd(II) were weakened in the presence of cations or
      humic acid, as a result of aggregation and less active site of Fe@SiO2. Overall,
      the simply prepared Fe@SiO2 were potential material for the heavy metals removed
      from water. 

PMID- 24455426
TI  - Rapid enzymatic method for pectin methyl esters determination.
AB  - Pectin is a natural polysaccharide used in food and pharma industries. Pectin
      degree of methylation is an important parameter having significant influence on
      pectin applications. A rapid, fully automated, kinetic flow method for
      determination of pectin methyl esters has been developed. The method is based on
      a lab-made analyzer using the reverse flow-injection/stopped flow principle.
      Methanol is released from pectin by pectin methylesterase in the first mixing
      coil. Enzyme working solution is injected further downstream and it is mixed with
      pectin/pectin methylesterase stream in the second mixing coil. Methanol is
      oxidized by alcohol oxidase releasing formaldehyde and hydrogen peroxide. This
      reaction is coupled to horse radish peroxidase catalyzed reaction, which gives
      the colored product 4-N-(p-benzoquinoneimine)-antipyrine. Reaction rate is
      proportional to methanol concentration and it is followed using Ocean Optics USB
      2000+ spectrophotometer. The analyzer is fully regulated by a lab written LabVIEW
      program. The detection limit was 1.47 mM with an analysis rate of 7 samples h(
      1). A paired t-test with results from manual method showed that the automated
      method results are equivalent to the manual method at the 95% confidence
      interval. The developed method is rapid and sustainable and it is the first
      application of flow analysis in pectin analysis. 

PMID- 24455427
TI  - Surfactant modified/mediated thin-layer chromatographic systems for the analysis
      of amino acids.
AB  - This review incorporates a large number of chromatographic systems modified by
      the surfactants. A large number of solvent systems and stationary phases are
      summarized in this paper. Three different kinds of surfactants (anionic,
      cationic, and nonionic) are used as modifiers for stationary phases as well as
      solvent systems. Surfactants are used at all the three different concentration
      levels (below, above, and at critical micelle concentration) where surfactants
      behave differently. Modifications of both stationary phases and solvent systems
      by surfactants produced a new generation of chromatographic systems.
      Microemulsion solvent systems are also incorporated in this paper. Microemulsion
      thin-layer chromatography is a new approach in the field of chromatography. 

PMID- 24455428
TI  - Intracellular regulation of matrix metalloproteinase-2 activity: new strategies
      in treatment and protection of heart subjected to oxidative stress.
AB  - Much is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R)
      injury. Under aerobic conditions, the heart prefers to metabolize fatty acids,
      which contribute to 60-80% of the required ATP. During ischemia, anaerobic
      glycolysis increases and becomes an important source of ATP for preservation of
      ion gradients. With reperfusion, fatty acid oxidation quickly recovers and again
      predominates as the major source of mitochondrial oxidative metabolism. Although
      a number of molecular mechanisms have been implicated in the development of I/R
      injury, their relative contributions remain to be determined. One such mechanism
      involves the proteolytic degradation of contractile proteins, such as troponin I
      (TnI), myosin heavy chain, titin, and the myosin light chains (MLC1 and MLC2) by
      matrix metalloproteinase-2 (MMP-2). However, very little is known about
      intracellular regulation of MMP-2 activity under physiological and pathological
      conditions. Greater understanding of the mechanisms that govern MMP-2 activity
      may lead to the development of new therapeutic strategies aimed at preservation
      of the contractile function of the heart subjected to myocardial infarction (MI)
      or I/R. This review discusses the intracellular mechanisms controlling MMP-2
      activity and highlights a new intracellular therapeutic direction for the
      prevention and treatment of heart injury. 

PMID- 24455429
TI  - The molecular epidemiology of chronic aflatoxin driven impaired child growth.
AB  - Aflatoxins are toxic secondary fungal metabolites that contaminate dietary
      staples in tropical regions; chronic high levels of exposure are common for many
      of the poorest populations. Observations in animals indicate that growth and/or
      food utilization are adversely affected by aflatoxins. This review highlights the
      development of validated exposure biomarkers and their use here to assess the
      role of aflatoxins in early life growth retardation. Aflatoxin exposure occurs in
      utero and continues in early infancy as weaning foods are introduced. Using
      aflatoxin-albumin exposure biomarkers, five major studies clearly demonstrate
      strong dose response relationships between exposure in utero and/or early infancy
      and growth retardation, identified by reduced birth weight and/or low HAZ and WAZ
      scores. The epidemiological studies include cross-sectional and longitudinal
      surveys, though aflatoxin reduction intervention studies are now required to
      further support these data and guide sustainable options to reduce the burden of
      exposure. The use of aflatoxin exposure biomarkers was essential in understanding
      the observational data reviewed and will likely be a critical monitor of the
      effectiveness of interventions to restrict aflatoxin exposure. Given that an
      estimated 4.5 billion individuals live in regions at risk of dietary
      contamination the public health concern cannot be over stated. 

PMID- 24455430
TI  - Spontaneous and procedural plaque embolisation in native coronary arteries:
      pathophysiology, diagnosis, and prevention.
AB  - The detachment of atherothrombotic material from the atherosclerotic coronary
      plaque and downstream embolisation is an underrecognized phenomenon and it causes
      different degrees of impairment of the coronary microcirculation. During
      treatment of obstructive atherosclerotic plaque by percutaneous coronary
      intervention (PCI) distal embolisation (DE) is considered to be inevitable and it
      is associated with potential clinical and prognostic implications. This review
      aims to assess the main aspects of both spontaneous and procedural DE, analyze
      their different pathophysiology, provide specific insights on the main diagnostic
      tools for their identification, and finally focus on the main strategies for
      their treatment and prevention. 

PMID- 24455431
TI  - Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein
      Structures and Molecular Mechanisms.
AB  - Cytochromes c (Cyt c) are ubiquitous heme-containing proteins, mainly involved in
      electron transfer processes, whose structure and functions have been and still
      are intensely studied. Surprisingly, our understanding of the molecular mechanism
      whereby the heme group is covalently attached to the apoprotein (apoCyt) in the
      cell is still largely unknown. This posttranslational process, known as Cyt c
      biogenesis or Cyt c maturation, ensures the stereospecific formation of the
      thioether bonds between the heme vinyl groups and the cysteine thiols of the
      apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic
      cells have evolved distinctive protein machineries composed of different
      proteins. In this review, the structural and functional properties of the main
      maturation apparatuses found in gram-negative and gram-positive bacteria and in
      the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c
      maturation process into three functional steps: (i) heme translocation and
      delivery, (ii) apoCyt thioreductive pathway, and (iii) apoCyt chaperoning and
      heme ligation. Moreover, current hypotheses and open questions about the
      molecular mechanisms of each of the three steps will be discussed, with special
      attention to System I, the maturation apparatus found in gram-negative bacteria. 

PMID- 24455432
TI  - Failure in asthma control: reasons and consequences.
AB  - Clinical research showed that asthma control is an achievable target. However,
      real-life observations suggest that a significant proportion of patients suffer
      from symptoms and report lifestyle limitations with a considerable burden on
      patient's quality of life. The achievement of asthma control is the result of the
      interaction among different variables concerning the disease pattern and
      patients' and physicians' knowledge and behaviour. The failure in asthma control
      can be considered as the result of the complex interaction among different
      variables, such as the role of guidelines diffusion and implementation, some
      disease-related factors (i.e., the presence of common comorbidities in asthma
      such as gastroesophageal reflux disease (GERD), sleep disturbances and
      obstructive sleep apnea (OSA), and rhinitis) or patient-related factors (i.e.,
      adherence to treatment, alexithymia, and coping strategies). Asthma control may
      be reached through a tailored treatment plan taking into account the complexity
      of factors that contribute to achieve and maintain this objective. 

PMID- 24455436
TI  - New Year's resolution in JPIS.

PMID- 24455435
TI  - The Role of Sialic Acid-Binding Receptors (Siglecs) in the Immunomodulatory
      Effects of Trypanosoma cruzi Sialoglycoproteins on the Protective Immunity of the
      Host.
AB  - Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is an
      important endemic infection in Latin America. Lately, it has also become a health
      concern in the United States and Europe. Most of the immunomodulatory mechanisms
      associated with this parasitic infection have been attributed to mucin-like
      molecules on the T. cruzi surface. Mucins are high molecular weight glycoproteins
      that are involved in regulating diverse cellular activities in both normal and
      pathological conditions. In Trypanosoma cruzi infection, the parasite-derived
      mucins are the main acceptors of sialic acid and it has been suggested that they
      play a role in various host-parasite interactions during the course of Chagas
      disease. Recently, we have presented evidence that sialylation of the mucins is
      required for the inhibitory effects on CD4(+) T cells. In what follows we propose
      that signaling via sialic acid-binding Ig-like lectin receptors for these highly
      sialylated structures on host cells contributes to the arrest of cell cycle
      progression in the G1 phase and may allow the parasite to modulate the immune
      system of the host. 

PMID- 24455434
TI  - The prevention of surgical site infection in elective colon surgery.
AB  - Infections at the surgical site continue to occur in as many as 20% of elective
      colon resection cases. Methods to reduce these infections are inconsistently
      applied. Surgical site infection (SSI) is the result of multiple interactive
      variables including the inoculum of bacteria that contaminate the site, the
      virulence of the contaminating microbes, and the local environment at the
      surgical site. These variables that promote infection are potentially offset by
      the effectiveness of the host defense. Reduction in the inoculum of bacteria is
      achieved by appropriate surgical site preparation, systemic preventive
      antibiotics, and use of mechanical bowel preparation in conjunction with the oral
      antibiotic bowel preparation. Intraoperative reduction of hematoma, necrotic
      tissue, foreign bodies, and tissue dead space will reduce infections. Enhancement
      of the host may be achieved by perioperative supplemental oxygenation,
      maintenance of normothermia, and glycemic control. These methods require
      additional research to identify optimum application. Uniform application of
      currently understood methods and continued research into new methods to reduce
      microbial contamination and enhancement of host responsiveness can lead to better
      outcomes. 

PMID- 24455437
TI  - Advances in the design of macroporous polymer scaffolds for potential
      applications in dentistry.
AB  - A paradigm shift is taking place in medicine and dentistry from using synthetic
      implants and tissue grafts to a tissue engineering approach that uses degradable
      porous three-dimensional (3D) material hydrogels integrated with cells and
      bioactive factors to regenerate tissues such as dental bone and other oral
      tissues. Hydrogels have been established as a biomaterial of choice for many
      years, as they offer diverse properties that make them ideal in regenerative
      medicine, including dental applications. Being highly biocompatible and similar
      to native extracellular matrix, hydrogels have emerged as ideal candidates in the
      design of 3D scaffolds for tissue regeneration and drug delivery applications.
      However, precise control over hydrogel properties, such as porosity, pore size,
      and pore interconnectivity, remains a challenge. Traditional techniques for
      creating conventional crosslinked polymers have demonstrated limited success in
      the formation of hydrogels with large pore size, thus limiting cellular
      infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the
      case of bone) of tissue-engineered constructs. Emerging technologies have
      demonstrated the ability to control microarchitectural features in hydrogels such
      as the creation of large pore size, porosity, and pore interconnectivity, thus
      allowing the creation of engineered hydrogel scaffolds with a structure and
      function closely mimicking native tissues. In this review, we explore the various
      technologies available for the preparation of macroporous scaffolds and their
      potential applications. 

PMID- 24455438
TI  - Photobiomodulation and implants: implications for dentistry.
AB  - The use of dental implants has become a mainstay of rehabilitative and
      restorative dentistry. With an impressive clinical success rate, there remain a
      few minor clinical issues with the use of implants such as peri-implant mucositis
      and peri-implantitis. The use of laser technology with implants has a fascinating
      breadth of applications, beginning from their precision manufacturing to clinical
      uses for surgical site preparation, reducing pain and inflammation, and promoting
      osseointegration and tissue regeneration. This latter aspect is the focus of this
      review, which outlines various studies of implants and laser therapy in animal
      models. The use of low level light therapy or photobiomodulation has demonstrated
      its efficacy in these studies. Besides more research studies to understand its
      molecular mechanisms, significant efforts are needed to standardize the clinical
      dosing and delivery protocols for laser therapy to ensure the maximal efficacy
      and safety of this potent clinical tool for photobiomodulation. 

PMID- 24455433
TI  - Type I Interferon at the Interface of Antiviral Immunity and Immune Regulation:
      The Curious Case of HIV-1.
AB  - Type I interferon (IFN-I) play a critical role in the innate immune response
      against viral infections. They actively participate in antiviral immunity by
      inducing molecular mechanisms of viral restriction and by limiting the spread of
      the infection, but they also orchestrate the initial phases of the adaptive
      immune response and influence the quality of T cell immunity. During infection
      with the human immunodeficiency virus type 1 (HIV-1), the production of and
      response to IFN-I may be severely altered by the lymphotropic nature of the
      virus. In this review I consider the different aspects of virus sensing, IFN-I
      production, signalling, and effects on target cells, with a particular focus on
      the alterations observed following HIV-1 infection. 

PMID- 24455439
TI  - Comparative evaluation of NovaMin desensitizer and Gluma desensitizer on dentinal
      tubule occlusion: a scanning electron microscopic study.
AB  - PURPOSE: In this study, the effect of calcium sodium phosphosilicate (NovaMin)
      desensitizing agent, which is a powder-based system, and hydroxyethyl
      methacrylate and glutaraldehyde (Gluma desensitizer), which is liquid-based
      system, on dentinal tubule occlusion was analyzed by scanning electron
      microscope. The effects of the above two along with one control group were
      compared to determine the more effective method of sealing the dentinal tubules
      after initial application. METHODS: Twenty specimens were allocated to each of 3
      groups: Control, Gluma desensitizer, and NovaMin. Two additional samples were
      also prepared and treated with Gluma and NovaMin; these samples were
      longitudinally fractured. The specimens were prepared from extracted sound human
      premolars and were stored in 10% formalin at room temperature. The teeth were
      cleaned of gross debris and then sectioned to provide one to two dentin
      specimens. The dentin specimens were etched with 6% citric acid for 2 minutes and
      rinsed in distilled water. Control discs were dried, and the test discs were
      treated with the desensitizing agents as per the manufacturer's instructions. The
      discs as well as longitudinal sections were later analyzed under the scanning
      electron microscope. The proportions of completely occluded, partially occluded,
      and open tubules within each group were calculated. The ratios of completely and
      partially occluded tubules to the total tubules for all the groups was
      determined, and the data was statistically analyzed using nonparametric tests and
      statistical significance was calculated. RESULTS: NovaMin showed more completely
      occluded tubules (0.545+/-0.051) while Gluma desensitizer showed more partially
      occluded tubules (0.532+/-0.075). The differences among all the groups were
      statistically significant (P<= 0.05). CONCLUSION: Both materials were effective
      in occluding dentinal tubules but NovaMin appeared more promising in occluding
      tubules completely after initial application.

PMID- 24455440
TI  - Analysis of periodontal attachment loss in relation to root form abnormalities.
AB  - PURPOSE: The aim of this study was to explore root shape abnormalities, to
      investigate the influence of root form abnormalities on periodontal attachment
      loss, and to gather basic data to assist in the diagnosis and treatment of
      aggressive periodontitis. METHODS: From January 2010 to June 2012, a survey was
      conducted of all 3,284 periodontitis patients who visited the Department of
      Periodontology, Daejeon Dental Hospital, Wonkwang University School of Dentistry.
      Clinical parameters (probing depth, periodontal attachment loss, missing teeth)
      were measured and a radiographic examination was performed at the baseline. We
      classified the root shape abnormality of bicuspids and molars based on Meng
      classification. RESULTS: The periodontal attachment loss was the highest at the
      maxillary first molar (6.03 mm). The loss of the second molar was prominent. Type
      V deformity was shown to be the most common in the second maxillary and
      mandibular molars (P<0.05). Type V root shape was associated with the highest
      attachment loss (P=0.01). CONCLUSIONS: Considering the small population and
      limited design of this study, definitive conclusions cannot be drawn. We suggest
      larger scale, methodologically more sophisticated studies that include normal
      controls and chronic periodontitis patients to clarify whether root form
      abnormalities are a potential risk factor for aggressive periodontitis.

PMID- 24455441
TI  - Association of gingival biotype with the results of scaling and root planing.
AB  - PURPOSE: The concept of gingival biotype has been used as a predictor of
      periodontal therapy outcomes since the 1980s. In the present study, prospective
      and controlled experiments were performed to compare periodontal pocket depth
      (PPD) reduction and gingival shrinkage (GSH) after scaling and root planing (SRP)
      according to gingival biotype. METHODS: Twenty-five patients diagnosed with
      chronic periodontitis participated in the present study. The PPD and GSH of the
      labial side of the maxillary anterior teeth (from the right canine to the left
      canine) were evaluated at baseline and 3 months after SRP. Changes in the PPD
      following SRP were classified into 4 groups according to the gingival thickness
      and initial PPD. Two more groups representing normal gingival crevices were added
      in evaluation of the GSH. The results were statistically analyzed using the
      independent t-test. RESULTS: In the end, 16 patients participated in the present
      study. With regard to PPD reduction, there were no significant differences
      according to gingival biotype (P>0.05). Likewise, sites with a PPD of over 3 mm
      failed to show any significant differences in the GSH (P>0.05). However, among
      the sites with a PPD of under 3 mm, those with the thin gingival biotype showed
      more GSH (P<0.05). CONCLUSIONS: PPD changes after SRP were not affected by
      gingival biotype with either shallow or deep periodontal pockets. GSH also showed
      equal outcomes in all the groups without normal gingival crevices. The results of
      SRP seem not to differ according to gingival biotype.

PMID- 24455442
TI  - Dissolution behavior and early bone apposition of calcium phosphate-coated
      machined implants.
AB  - PURPOSE: Calcium phosphate (CaP)-coated implants promote osseointegration and
      survival rate. The aim of this study was to (1) analyze the dissolution behavior
      of the residual CaP particles of removed implants and (2) evaluate bone
      apposition of CaP-coated machined surface implants at the early healing phase.
      METHODS: Mandibular premolars were extracted from five dogs. After eight weeks,
      the implants were placed according to drilling protocols: a nonmobile implant
      (NI) group and rotational implant (RI) group. For CaP dissolution behavior
      analysis, 8 implants were removed after 0, 1, 2, and 4 weeks. The surface
      morphology and deposition of the coatings were observed. For bone apposition
      analysis, block sections were obtained after 1-, 2-, and 4-week healing periods
      and the specimens were analyzed. RESULTS: Calcium and phosphorus were detected in
      the implants that were removed immediately after insertion, and the other
      implants were composed mainly of titanium. There were no notable differences
      between the NI and RI groups in terms of the healing process. The bone-to-implant
      contact and bone density in the RI group showed a remarkable increase after 2
      weeks of healing. CONCLUSIONS: It can be speculated that the CaP coating
      dissolves early in the healing phase and chemically induces early bone formation
      regardless of the primary stability.

PMID- 24455443
TI  - The effect of pretreating resorbable blast media titanium discs with an
      ultrasonic scaler or toothbrush on the bacterial removal efficiency of brushing.
AB  - PURPOSE: This in vitro study was performed to assess the adherence of
      Porphyromonas gingivalis to a resorbable blast media (RBM) titanium surface
      pretreated with an ultrasonic scaler or toothbrush and to evaluate the effects of
      the treatment of the RBM titanium discs on the bacterial removal efficiency of
      brushing by crystal violet assay and scanning electron microscopy. METHODS: RBM
      titanium discs were pretreated with one of several ultrasonic scaler tips or
      cleaned with a toothbrush. Then the titanium discs were incubated with P.
      gingivalis and the quantity of adherent bacteria was compared. The disc surfaces
      incubated with bacteria were brushed with a toothbrush with dentifrice. Bacteria
      remaining on the disc surfaces were quantified. RESULTS: A change in morphology
      of the surface of the RBM titanium discs after different treatments was noted.
      There were no significant differences in the adherence of bacteria on the
      pretreated discs according to the treatment modality. Pretreatment with various
      instruments did not produce significant differences in the bacterial removal
      efficiency of brushing with dentifrice. CONCLUSIONS: Within the limits of this
      study, various types of mechanical instrumentation were shown to cause mechanical
      changes on the RBM titanium surface but did not show a significant influence on
      the adherence of bacteria and removal efficiency of brushing.

PMID- 24455444
TI  - Assessment of dentists' subjective satisfaction with a newly developed device for
      maxillary sinus membrane elevation by the crestal approach.
AB  - PURPOSE: The purposes of this study were to assess the dentists' subjective
      satisfaction with the crestal approach sinus (CAS) kit, a device for maxillary
      sinus membrane elevation by the crestal approach using a special drilling system
      and hydraulic pressure, and to summarize the subjective satisfaction of dental
      implants placed after a sinus lift procedure with the CAS kit. METHODS: Thirty
      dental clinicians who had experience with dental implant placement after a sinus
      lift procedure with the CAS kit from June 2010 to May 2012 were included in this
      study. The questionnaire for the evaluation of the dentists' subjective
      satisfaction with the CAS kit was sent to the respondents and returned. The
      questionnaire was composed of two main parts. The first part was related to the
      sinus membrane perforation rate. The second part was related to the dentists'
      subjective satisfaction with the CAS kit. RESULTS: A total of 28 dentists
      answered the questionnaire. Among 924 implant cases, sinus membrane perforation
      occurred in 38 cases (4.1%). Among the 28 dentists, 26 dentists (92.9%) were
      satisfied or very satisfied with the CAS kit. In particular, 24 dentists (85.7%)
      reported that safety, cutting performance, and user-friendliness of the CAS drill
      were advantages of the CAS kit. However, 7 dentists (25%) did not routinely use
      the hydraulic lifter for sinus membrane elevation. CONCLUSIONS: From the survey,
      it was shown that the respondents were generally satisfied with the CAS kit and
      that the cutting performance and safety of the drill component were considered
      strengths of the CAS kit.

PMID- 24455445
TI  - Periodontal regeneration with nano-hyroxyapatite-coated silk scaffolds in dogs.
AB  - PURPOSE: In this study, we investigated the effect of silk scaffolds on one-wall
      periodontal intrabony defects. We conjugated nano-hydroxyapatite (nHA) onto a
      silk scaffold and then seeded periodontal ligament cells (PDLCs) or dental pulp
      cells (DPCs) onto the scaffold. METHODS: Five dogs were used in this study.
      Bilateral 4 mm*2 mm (depth*mesiodistal width), one-wall intrabony periodontal
      defects were surgically created on the distal side of the mandibular second
      premolar and the mesial side of the mandibular fourth premolar. In each dog, four
      of the defects were separately and randomly assigned to the following groups: the
      PDLC-cultured scaffold transplantation group (PDLC group), the DPC-cultured
      scaffold transplantation group (DPC group), the normal saline-soaked scaffold
      transplantation group, and the control group. The animals were euthanized
      following an 8-week healing interval for clinical, scanning electron microscopy
      (SEM), and histologic evaluations. RESULTS: There was no sign of inflammation or
      other clinical signs of postoperative complications. The examination of cell
      seeded constructs by SEM provided visual confirmation of the favorable
      characteristics of nHA-coated silk scaffolds for tissue engineering. The
      scaffolds exhibited a firm connective porous structure in cross section, and
      after PDLCs and DPCs were seeded onto the scaffolds and cultured for 3 weeks, the
      attachment of well-spread cells and the formation of extracellular matrix (ECM)
      were observed. The histologic analysis revealed that a well-maintained grafted
      volume was present at all experimental sites for 8 weeks. Small amounts of
      inflammatory cells were seen within the scaffolds. The PDLC and DPC groups did
      not have remarkably different histologic appearances. CONCLUSIONS: These
      observations indicate that nHA-coated silk scaffolds can be considered to be
      potentially useful biomaterials for periodontal regeneration.

PMID- 24455446
TI  - Severe Hypertriglyceridemia Causing Acute Pancreatitis in a Child with New Onset
      Type I Diabetes Mellitus Presenting in Ketoacidosis.
AB  - A 10 year old girl presented with severe diabetic ketoacidosis (DKA) and a
      hemoglobin A1C of 17.9%. On hospital day 2 after acidosis had improved it
      worsened and she developed excruciating abdominal pain. Her serum triglycerides
      and lipase levels were found to be extremely high and ultrasound analysis of the
      pancreas was consistent with acute pancreatitis. She was diagnosed with acute
      pancreatitis secondary to hypertriglyceridemia. The pancreatitis resolved
      completely and two months later her hemoglobin A1C was 8.2% and the serum
      triglycerides were normal. Severe hypertriglyceridemia from insulin deficiency
      causing pancreatitis in new onset type 1 diabetes mellitus is a rare but serious
      complication of DKA in children.

PMID- 24455447
TI  - HIV Risk Behaviors among African American Women with at-Risk Male Partners.
AB  - BACKGROUND: HIV continues to impact African American women at alarming rates.
      Yet, few researchers have examined the relationship factors promoting unprotected
      sex within African American communities, especially instances in which women are
      aware that their male partners are engaging in high risk behaviors. This
      qualitative study explored the sexual behaviors, relationship characteristics,
      and HIV prevention strategies utilized by African American women in relationships
      with African American men at-risk for HIV. METHOD: To understand the issues that
      should be addressed in a sexual risk-reduction intervention, data were collected
      from three, two-hour focus group discussions (n=24) comprised primarily of low
      income African American women with histories of at-risk male sex partners. At
      risk partners included specifically men who had sex with other men or with
      transgender individuals, used crack cocaine or injection drugs, had lengthy
      incarceration periods, or an unknown sexual history. Discussion questions
      examined external factors affecting sexual risk behaviors such as societal
      pressures, peer norms, and financial vulnerability. Discussions were audiotaped,
      transcribed, and analyzed using a consensual qualitative research approach.
      RESULTS: Five themes, including self-esteem, social influences on behavior,
      relationship fidelity, sexual risk behavior, and partners' sexual behaviors, were
      identified as placing women at increased risk for HIV. Reasons for inconsistent
      condom use included concern for maintaining the relationship and substance use
      before and during sex. African American women also believed that men who have sex
      with men and women (MSMW) were dishonest about their sexuality due to stigma
      towards homosexuality/bisexuality. Despite these challenges, participants
      indicated that African American women have a strong sense of pride that can
      positively impact behaviors in relationships. CONCLUSION: The findings of this
      study support that social and contextual factor such as emotional and financial
      issues, culture, history, and relationship dynamics need to be considered when
      developing tailored sexual health interventions for this population.

PMID- 24455448
TI  - Risk of Death among HIV Co-Infected Multidrug Resistant Tuberculosis Patients,
      Compared To Mortality in the General Population of South Africa.
AB  - BACKGROUND: Even though highly effective drugs are available in South Africa,
      multidrug resistant tuberculosis (MDR-TB) patients with HIV infection have higher
      mortality compared to HIV-uninfected MDR-TB patients. This trend has been
      observed in similar countries with high HIV prevalence. This study sought to
      determine excess mortality attributable to HIV among MDR-TB patients in South
      Africa using relative survival methods. METHODS: Data available were from a
      cohort of 2079 MDR-TB patients enrolled in a Standardized Programmatic Management
      of MDR-TB from 2000 to 2004 in South Africa. A Poisson-based model adjusted for
      age, gender, year of diagnosis, TB history, and resistance to ethambutol, anti-TB
      injectable drugs and fluoroquinolones antibiotics was constructed to assess the
      excess mortality among HIV co-infected MDR-TB patients. Excess hazard ratios
      (EHRs) were used to describe the effect of the predictors on net mortality,
      controlling for the general mortality in the South African population. RESULTS:
      Death was recorded on 1619 patients, of whom 367 (22.7%) had died within 2 years.
      Out of the 1413 patients that tested for HIV infection, 554 (39.2%) tested
      positive. Excess mortality was higher in HIV infected, compared to HIV
      uninfected, MDR-TB patients (adjusted excess hazard ratio, 5.6 [95% CI, 3.2
      9.7]); in patients whose TB isolates' resistance to ethambutol and kanamycin was
      unknown (3.7 [2.1-6.2] and 4.87 [1.9-13.3], respectively) vs. known. There were
      no differences in excess mortality between age and gender of the patient, year of
      diagnosis and TB history. CONCLUSION: Adjusting for some important predictors,
      MDR-TB patients with HIV infection experienced higher excess mortality compared
      to HIV-uninfected MDR-TB patients, after accounting for the general mortality in
      South Africa. An appropriate, though complex method has produced predictor effect
      estimates similar to those obtained from classical methods. Thus, the use of
      relative survival methods should be encouraged in the analysis of causespecific
      mortality, when ascertainment of cause of death is inaccurate or unknown.

PMID- 24455449
TI  - Are Low- and Middle-Income Countries Repeating Mistakes Made by High-Income
      Countries in the Control of HIV for Men who have Sex with Men?

PMID- 24455450
TI  - Unusual wrist tremor: unilateral isometric tremor?
AB  - BACKGROUND: Tremors may be difficult to classify. CASE REPORT: An 83-year-old
      male presented with an unusual left wrist tremor. The tremor could be
      reproducibly elicited by making a fist or carrying a weighted object (e.g., a
      shopping bag, bottle of water) of approximately 1 lb or more, and it intensified
      with heavier weights. The tremor was difficult to classify, although it shared
      features with isometric tremor. DISCUSSION: This specific presentation of tremor
      has not been reported previously. We hope that the detailed description we
      provide will aid other neurologists who encounter this or similar tremors in
      their clinics.

PMID- 24455451
TI  - Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after
      intratracheal instillation in rats.
AB  - Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their
      usage in medical applications and consumer products is growing rapidly. To
      evaluate possible adverse health effects, especially to the lungs, the current
      study focused on the cytotoxic and proinflammatory effects of AgNP after the
      intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm) showing
      little agglomeration in aqueous suspension were instilled intratracheally. After
      24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH), total protein,
      and cytokine levels as well as total and differential cell counts were measured
      in the bronchoalveolar lavage fluid (BALF). Instillation of 50 ug PVP-AgNP did
      not result in elevated LDH, total protein, or cytokine levels in BALF compared to
      the control, whereas instillation of 250 ug PVP-AgNP caused a significant
      increase in LDH (1.9-fold) and total protein (1.3-fold) levels as well as in
      neutrophil numbers (60-fold) of BALF. Furthermore, while there was no change in
      BALF cytokine levels after the instillation of 50 ug PVP-AgNP, instillation of
      250 ug PVP-AgNP resulted in significantly increased levels of seven out of eleven
      measured cytokines. These finding suggest that exposure to inhaled AgNP can
      induce moderate pulmonary toxicity, but only at rather high concentrations. 

PMID- 24455452
TI  - Structural development and energy dissipation in simulated silicon apices.
AB  - In this paper we examine the stability of silicon tip apices by using density
      functional theory (DFT) calculations. We find that some tip structures - modelled
      as small, simple clusters - show variations in stability during manipulation
      dependent on their orientation with respect to the sample surface. Moreover, we
      observe that unstable structures can be revealed by a characteristic hysteretic
      behaviour present in the F(z) curves that were calculated with DFT, which
      corresponds to a tip-induced dissipation of hundreds of millielectronvolts
      resulting from reversible structural deformations. Additionally, in order to
      model the structural evolution of the tip apex within a low temperature NC-AFM
      experiment, we simulated a repeated tip-surface indentation until the tip
      structure converged to a stable termination and the characteristic hysteretic
      behaviour was no longer observed. Our calculations suggest that varying just a
      single rotational degree of freedom can have as measurable an impact on the tip
      surface interaction as a completely different tip structure. 

PMID- 24455453
TI  - Preparation of NiS/ZnIn2S4 as a superior photocatalyst for hydrogen evolution
      under visible light irradiation.
AB  - In this study, NiS/ZnIn2S4 nanocomposites were successfully prepared via a facile
      two-step hydrothermal process. The as-prepared samples were characterized by X
      ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission
      electron microscopy (TEM) and high-resolution transmission electron microscopy
      (HRTEM). Their photocatalytic performance for hydrogen evolution under visible
      light irradiation was also investigated. It was found that the photocatalytic
      hydrogen evolution activity over hexagonal ZnIn2S4 can be significantly increased
      by loading NiS as a co-catalyst. The formation of a good junction between ZnIn2S4
      and NiS via the two step hydrothermal processes is beneficial for the directional
      migration of the photo-excited electrons from ZnIn2S4 to NiS. The highest
      photocatalytic hydrogen evolution rate (104.7 MUmol/h), which is even higher than
      that over Pt/ZnIn2S4 nanocomposite (77.8 MUmol/h), was observed over an optimum
      NiS loading amount of 0.5 wt %. This work demonstrates a high potential of the
      developing of environmental friendly, cheap noble-metal-free co-catalyst for
      semiconductor-based photocatalytic hydrogen evolution. 

PMID- 24455454
TI  - Some reflections on the understanding of the oxygen reduction reaction at
      Pt(111).
AB  - The oxygen reduction reaction (ORR) is a pivotal process in electrochemistry.
      Unfortunately, after decades of intensive research, a fundamental knowledge about
      its reaction mechanism is still lacking. In this paper, a global and critical
      view on the most important experimental and theoretical results regarding the ORR
      on Pt(111) and its vicinal surfaces, in both acidic and alkaline media, is taken.
      Phenomena such as the ORR surface structure sensitivity and the lack of a
      reduction current at high potentials are discussed in the light of the surface
      oxidation and disordering processes and the possible relevance of the hydrogen
      peroxide reduction and oxidation reactions in the ORR mechanism. The necessity to
      build precise and realistic reaction models, which are deducted from reliable
      experimental results that need to be carefully taken under strict working
      conditions is shown. Therefore, progress in the understanding of this important
      reaction on a molecular level, and the choice of the right approach for the
      design of the electrocatalysts for fuel-cell cathodes is only possible through a
      cooperative approach between theory and experiments. 

PMID- 24455455
TI  - Static analysis of rectangular nanoplates using trigonometric shear deformation
      theory based on nonlocal elasticity theory.
AB  - In this article, a new higher order shear deformation theory based on
      trigonometric shear deformation theory is developed. In order to consider the
      size effects, the nonlocal elasticity theory is used. An analytical method is
      adopted to solve the governing equations for static analysis of simply supported
      nanoplates. In the present theory, the transverse shear stresses satisfy the
      traction free boundary conditions of the rectangular plates and these stresses
      can be calculated from the constitutive equations. The effects of different
      parameters such as nonlocal parameter and aspect ratio are investigated on both
      nondimensional deflections and deflection ratios. It may be important to mention
      that the present formulations are general and can be used for isotropic,
      orthotropic and anisotropic nanoplates. 

PMID- 24455456
TI  - Dye-doped spheres with plasmonic semi-shells: Lasing modes and scattering at
      realistic gain levels.
AB  - We numerically simulate the compensation of absorption, the near-field
      enhancement as well as the differential far-field scattering cross section for
      dye-doped polystyrene spheres (radius 195 nm), which are half-covered by a silver
      layer of 10-40 nm thickness. Such silver capped spheres are interesting
      candidates for nanoplasmonic lasers, so-called spasers. We find that spasing
      requires gain levels less than 3.7 times higher than those in commercially
      available dye-doped spheres. However, commercially available concentrations are
      already apt to achieve negative absorption, and to narrow and enhance scattering
      by higher order modes. Narrowing of the plasmonic modes by gain also makes
      visible higher order modes, which are normally obscured by the broad spectral
      features of the lower order modes. We further show that the angular distribution
      of the far-field scattering of the spasing modes is by no means dipole-like and
      is very sensitive to the geometry of the structure. 

PMID- 24455457
TI  - Noise performance of frequency modulation Kelvin force microscopy.
AB  - Noise performance of a phase-locked loop (PLL) based frequency modulation Kelvin
      force microscope (FM-KFM) is assessed. Noise propagation is modeled step by step
      throughout the setup using both exact closed loop noise gains and an
      approximation known as "noise gain" from operational amplifier (OpAmp) design
      that offers the advantage of decoupling the noise performance study from
      considerations of stability and ideal loop response. The bandwidth can be chosen
      depending on how much noise is acceptable and it is shown that stability is not
      an issue up to a limit that will be discussed. With thermal and detector noise as
      the only sources, both approaches yield PLL frequency noise expressions equal to
      the theoretical value for self-oscillating circuits and in agreement with
      measurement, demonstrating that the PLL components neither modify nor contribute
      noise. Kelvin output noise is then investigated by modeling the surrounding bias
      feedback loop. A design rule is proposed that allows choosing the AC modulation
      frequency for optimized sharing of the PLL bandwidth between Kelvin and
      topography loops. A crossover criterion determines as a function of bandwidth,
      temperature and probe parameters whether thermal or detector noise is the
      dominating noise source. Probe merit factors for both cases are then established,
      suggesting how to tackle noise performance by probe design. Typical merit factors
      of common probe types are compared. This comprehensive study is an encouraging
      step toward a more integral performance assessment and a remedy against focusing
      on single aspects and optimizing around randomly chosen key values. 

PMID- 24455458
TI  - Many-body effects in semiconducting single-wall silicon nanotubes.
AB  - The electronic and optical properties of semiconducting silicon nanotubes (SiNTs)
      are studied by means of the many-body Green's function method, i.e., GW
      approximation and Bethe-Salpeter equation. In these studied structures, i.e.,
      (4,4), (6,6) and (10,0) SiNTs, self-energy effects are enhanced giving rise to
      large quasi-particle (QP) band gaps due to the confinement effect. The strong
      electron-electron (e-e) correlations broaden the band gaps of the studied SiNTs
      from 0.65, 0.28 and 0.05 eV at DFT level to 1.9, 1.22 and 0.79 eV at GW level.
      The Coulomb electron-hole (e-h) interactions significantly modify optical
      absorption properties obtained at noninteracting-particle level with the
      formation of bound excitons with considerable binding energies (of the order of 1
      eV) assigned: the binding energies of the armchair (4,4), (6,6) and zigzag (10,0)
      SiNTs are 0.92, 1.1 and 0.6 eV, respectively. Results in this work are useful for
      understanding the physics and applications in silicon-based nanoscale device
      components. 

PMID- 24455459
TI  - Surface assembly and nanofabrication of 1,1,1-tris(mercaptomethyl)heptadecane on
      Au(111) studied with time-lapse atomic force microscopy.
AB  - The solution self-assembly of multidentate organothiols onto Au(111) was studied
      in situ using scanning probe nanolithography and time-lapse atomic force
      microscopy (AFM). Self-assembled monolayers (SAMs) prepared from dilute solutions
      of multidentate thiols were found to assemble slowly, requiring more than six
      hours to generate films. A clean gold substrate was first imaged in ethanolic
      media using liquid AFM. Next, a 0.01 mM solution of multidentate thiol was
      injected into the liquid cell. As time progressed, molecular-level details of the
      surface changes at different time intervals were captured by successive AFM
      images. Scanning probe based nanofabrication was accomplished using protocols of
      nanografting and nanoshaving with n-alkanethiols and a tridentate molecule, 1,1,1
      tris(mercaptomethyl)heptadecane (TMMH). Nanografted patterns of TMMH could be
      inscribed within n-alkanethiol SAMs; however, the molecular packing of the
      nanopatterns was less homogeneous compared to nanopatterns produced with
      monothiolates. The multidentate molecules have a more complex assembly pathway
      than monothiol counterparts, mediated by sequential steps of forming S-Au bonds
      to the substrate. 

PMID- 24455460
TI  - Exploring the retention properties of CaF2 nanoparticles as possible additives
      for dental care application with tapping-mode atomic force microscope in liquid.
AB  - Amplitude-modulation atomic force microscopy (AM-AFM) is used to determine the
      retention properties of CaF2 nanoparticles adsorbed on mica and on tooth enamel
      in liquid. From the phase-lag of the forced cantilever oscillation the local
      energy dissipation at the detachment point of the nanoparticle was determined.
      This enabled us to compare different as-synthesized CaF2 nanoparticles that vary
      in shape, size and surface structure. CaF2 nanoparticles are candidates for
      additives in dental care products as they could serve as fluorine-releasing
      containers preventing caries during a cariogenic acid attack on the teeth. We
      show that the adherence of the nanoparticles is increased on the enamel substrate
      compared to mica, independently of the substrate roughness, morphology and size
      of the particles. 

PMID- 24455461
TI  - Interleukin-6: a potent biomarker of mycobacterial infection.
AB  - BACKGROUND: Human tuberculosis (TB), a chronic inflammatory disease is caused by
      Mycobacterium tuberculosis, a facultative intramacrophage pathogen. The highly
      complex interactions between mycobacteria and macrophages (MPhis), characterized
      in part by the induction and elaboration of several cytokines including IL-1, IL
      6, IL-10, IL-12 p40 and IL-12 p70 are not yet fully understood. The cytokines are
      known to have important bearing on the pathogenesis and host defense during TB.
      We thus studied different patterns of cytokines elaborated by mouse peritoneal
      macrophages (PMs) following their interaction with live and heat-killed, virulent
      and avirulent, and pathogenic and non-pathogenic mycobacteria, in vitro.
      MATERIALS AND METHODS: Pathogenic M. tuberculosis H37Rv (virulent) and M.
      tuberculosis H37Ra (avirulent), and non-pathogenic M. smegmatis were grown in
      complete Middle Brook 7H9 broth. For some experiments, mycobacteria were heat
      killed (80 degrees C; 20 min). The supernatants of cultured PMs, having ingested
      mycobacteria for 6 h, 24 h, 4 days and 7 days, were harvested for the
      quantification of IL-1, IL-6, IL-10, IL-12 p40 and IL-12 p70 by using a multiplex
      suspension cytokine array system. RESULTS: The PMs infected with heat-killed
      mycobacteria, as compared to their respective live counterparts, invariably
      elaborated significantly (p < 0.001) increased (approximately 2-3-fold) amounts
      of IL-6, at all the time-points studied, in vitro. Further, PMs infected with M.
      tuberculosis H37Ra, as compared to M. tuberculosis H37Rv, elaborated 4-5-fold
      more (p < 0.001) IL-6. Non-pathogenic M. smegmatis, as compared to pathogenic M.
      tuberculosis H37Ra and M. tuberculosis H37Rv, following infection, induced the
      PMs to elaborate highest (p < 0.001) amounts of IL-6 at all the time-points
      studied. Curiously, none of these mycobacteria-infected PMs elaborated IL-1, IL
      10, IL-12 p40 and IL-12 p70, significantly. CONCLUSION: IL-6 appears to be the
      only major cytokine elaborated by mycobacteria-infected PMs, in vitro, and thus
      may function as a potent biomarker of mycobacterial infection, either stand-alone
      or along with other cytokines.

PMID- 24455462
TI  - Panel of polymorphic heterologous microsatellite loci to genotype critically
      endangered Bengal tiger: a pilot study.
AB  - In India, six landscapes and source populations that are important for long-term
      conservation of Bengal tigers (Panthera tigris tigris) have been identified.
      Except for a few studies, nothing is known regarding the genetic structure and
      extent of gene flow among most of the tiger populations across India as the
      majority of them are small, fragmented and isolated. Thus, individual-based
      relationships are required to understand the species ecology and biology for
      planning effective conservation and genetics-based individual identification has
      been widely used. But this needs screening and describing characteristics of
      microsatellite loci from DNA from good-quality sources so that the required
      number of loci can be selected and the genotyping error rate minimized. In the
      studies so far conducted on the Bengal tiger, a very small number of loci (n =
      35) have been tested with high-quality source of DNA, and information on locus
      specific characteristics is lacking. The use of such characteristics has been
      strongly recommended in the literature to minimize the error rate and by the
      International Society for Forensic Genetics (ISFG) for forensic purposes.
      Therefore, we describe for the first time locus-specific genetic and genotyping
      profile characteristics, crucial for population genetic studies, using high
      quality source of DNA of the Bengal tiger. We screened 39 heterologous
      microsatellite loci (Sumatran tiger, domestic cat, Asiatic lion and snow leopard)
      in captive individuals (n = 8), of which 21 loci are being reported for the first
      time in the Bengal tiger, providing an additional choice for selection. The mean
      relatedness coefficient (R = -0.143) indicates that the selected tigers were
      unrelated. Thirty-four loci were polymorphic, with the number of alleles ranging
      from 2 to 7 per locus, and the remaining five loci were monomorphic. Based on the
      PIC values (> 0.500), and other characteristics, we suggest that 16 loci (3 to 7
      alleles) be used for genetic and forensic study purposes. The probabilities of
      matching genotypes of unrelated individuals (3.692 * 10(-19)) and siblings (4.003
      * 10(-6)) are within the values needed for undertaking studies in population
      genetics, relatedness, sociobiology and forensics. 

PMID- 24455463
TI  - Significant dose Escalation of Idarubicin in the treatment of aggressive Non-
      Hodgkin Lymphoma leads to increased hematotoxicity without improvement in
      efficacy in comparison to standard CHOEP-14: 9-year follow up results of the
      CIVEP trial of the DSHNHL.
AB  - BACKGROUND: Dose escalation and modification of CHOP has improved the prognosis
      of patients with aggressive lymphoma; even in the rituximab era, dose escalation
      for high-risk patients is exploited and frequently limited by drug toxicity.
      Idarubicin (Id) is a 4-demethoxy anthracycline analogue of daunorubicin with
      activity against lymphoma and has been reported to cause less cardiotoxicity than
      other anthracylines. The aim of this study was to replace doxorubicine with
      idarubicin in the CHOEP regimen and to find the maximum tolerable dose (MTD) of
      idarubicin based on hematotoxicity. PATIENTS AND METHODS: Between 11/96 and
      09/98, 64 patients (pts) aged 18-75 yrs (pts. 18-60, LDH not elevated, >60 years
      all risk groups) with newly diagnosed aggressive lymphoma received 6 cycles of
      CIVEP-14 with an escalating dose of idarubicin, consisting of idarubicin (11-16
      mg/m(2) d1) and standard doses of cyclophosphamide, vincristine, etoposide, and
      prednisone with G-CSF support. RESULTS: 55 pts (median age 56 yrs) were evaluable
      for a final analysis with a median observation time of 9.3 years. The CR-rate was
      77.4% ; the 5 and 8-year-EFS rates were 46.4% (95%CI 32.5-60.3%) and 43.5% (29.4
      57.6%), respectively, and the 5- and 8 yr OS rates were 64.6% (51.7-77.5%) and
      59.9% (46.4-73.4%). 14/55 patients have died due to lymphoma progression, and
      2/55 patients (3.6%) due to treatment related toxicity, 4/55 due to other causes
      (3 infections, 1 acute heart failure). In a matched pair analysis comparing CHOEP
      14 and CIVEP-14, CIVEP-14 had a higher hematotoxicity with no significant
      differences in the event free and overall survival for the two regimens.
      CONCLUSIONS: Thus, idarubicin cannot be used instead doxorubicin even if its dose
      is escalated to achieve similar hematotoxicity. Doxorubicin remains the standard
      anthracycline for the treatment of aggressive NHL.

PMID- 24455464
TI  - A comparative study of fluoride ingestion levels, serum thyroid hormone & TSH
      level derangements, dental fluorosis status among school children from endemic
      and non-endemic fluorosis areas.
AB  - The study was undertaken to determine serum/urinary fluoride status and
      comparison of free T4, free T3 and thyroid stimulating hormone levels of 8 to 15
      years old children with and without dental fluorosis living in an endemic and non
      endemic fluorosis area. A sample group of 60 male and female school children,
      with or without dental fluorosis, consuming fluoride-contaminated water in
      endemic fluoride area of Udaipur district, Rajasthan were selected through a
      school dental fluorosis survey. The sample of 10 children of same age and socio
      economic status residing in non endemic areas who did not have dental fluorosis
      form controls. Fluoride determination in drinking water, urine and blood was done
      with Ion 85 Ion Analyzer Radiometer with Hall et al. method. The thyroid gland
      functional test was done by Immonu Chemiluminiscence Micropartical Assay with
      Bayer Centaur Autoanalyzer. The significantly altered FT3, FT4 and TSH hormones
      level in both group1A and 1B school children were noted. The serum and urine
      fluoride levels were found to be increased in both the groups. A significant
      relationship of water fluoride to urine and serum fluoride concentration was
      seen. The serum fluoride concentration also had significant relationship with
      thyroid hormone (FT3/FT4) and TSH concentrations. The testing of drinking water
      and body fluids for fluoride content, along with FT3, FT4, and TSH in children
      with dental fluorosis is desirable for recognizing underlying thyroid
      derangements and its impact on fluorosis. 

PMID- 24455465
TI  - Successful use of eculizumab in an 86-year-old patient with paroxysmal nocturnal
      hemoglobinuria in Japan.
AB  - Eculizumab was used to treat an 86-year-old male patient with paroxysmal
      nocturnal hemoglobinuria, the oldest reported case in Japan. As observed in
      younger patients, this drug rapidly suppressed hemolysis in the present patient,
      which allowed weaning from blood transfusion. Eculizumab treatment has been
      continued for 2 years and resulted in the alleviation of renal dysfunction.
      Despite the patient's advanced age, the inhibition of complement activity caused
      by this drug did not result in infection, indicating that it is safe to use in
      elderly patients. 

PMID- 24455466
TI  - Design of a reversible single precision floating point subtractor.
AB  - In recent years, Reversible logic has emerged as a major area of research due to
      its ability to reduce the power dissipation which is the main requirement in the
      low power digital circuit design. It has wide applications like low power CMOS
      design, Nano-technology, Digital signal processing, Communication, DNA computing
      and Optical computing. Floating-point operations are needed very frequently in
      nearly all computing disciplines, and studies have shown floating-point
      addition/subtraction to be the most used floating-point operation. However, few
      designs exist on efficient reversible BCD subtractors but no work on reversible
      floating point subtractor. In this paper, it is proposed to present an efficient
      reversible single precision floating-point subtractor. The proposed design
      requires reversible designs of an 8-bit and a 24-bit comparator unit, an 8-bit
      and a 24-bit subtractor, and a normalization unit. For normalization, a 24-bit
      Reversible Leading Zero Detector and a 24-bit reversible shift register is
      implemented to shift the mantissas. To realize a reversible 1-bit comparator, in
      this paper, two new 3x3 reversible gates are proposed The proposed reversible 1
      bit comparator is better and optimized in terms of the number of reversible gates
      used, the number of transistor count and the number of garbage outputs. The
      proposed work is analysed in terms of number of reversible gates, garbage
      outputs, constant inputs and quantum costs. Using these modules, an efficient
      design of a reversible single precision floating point subtractor is proposed.
      Proposed circuits have been simulated using Modelsim and synthesized using Xilinx
      Virtex5vlx30tff665-3. The total on-chip power consumed by the proposed 32-bit
      reversible floating point subtractor is 0.410 W. 

PMID- 24455467
TI  - Effect of fibrate treatment on liver function tests in patients with the
      metabolic syndrome.
AB  - BACKGROUND: Fibrates are used especially in patients with hypertriglyceridaemia,
      a feature of the metabolic syndrome. Elevated LFTs are often observed in these
      patients perhaps related to fatty infiltration. AIM: We wished to study changes
      seen in LFTs (GGT, ALT and ALP) following fibrate therapy and then determine
      associated factors. METHODS: This was a retrospective observational study in
      which data was collected from case notes of patients started on fibrates (n =
      118, 2002-2008) in the lipid clinic at Good Hope Hospital and pre/post-fibrate
      lipid and LFT values were obtained. All biochemistry was performed on the Roche P
      Unit using supplied reagents. Statistical analyses included t tests and
      regression analyses (factorised when quartiles were compared). RESULTS: Of the
      study population 106 patients were on fenofibrate; the remaining on bezafibrate.
      Significant lowering of GGT (p < 0.0001), ALT (p = 0.0014) and ALP (p < 0.0001)
      levels were observed following fibrate treatment. Baseline lipid (cholesterol,
      triglycerides and HDL) concentrations, alcohol intake, length of treatment,
      gender, concurrent statin treatment and diabetes did not correlate with these
      changes in LFT in a multiple regression analysis. Higher pre-fibrate GGT (p <
      0.0001), ALT (p < 0.0001) and ALP (p < 0.0001) concentrations were associated
      with larger decreases in each of these tests respectively with the highest 2
      quartiles (GGT > 57 IU/l, ALT > 34 IU/l and ALP > 94 IU/l) significantly
      different to the lowest quartile. The above associations remained significant
      even when the regression analyses were corrected for changes in lipid values
      (which did not show an association). CONCLUSIONS: Fibrate treatment led to
      improvements in LFT, the greatest benefit seen in patients with higher baseline
      LFT values. It appears that baseline and changes in lipid values post fibrate
      treatment were not associated with change in LFT.

PMID- 24455468
TI  - Sergei Prokofiev's Children's Pieces, Op. 65: a comprehensive approach to
      learning about a composer and his works: biography, style, form and analysis.
AB  - This article is written for the benefit of piano teachers and students, but can
      be of benefit to any music teacher or student. It is a case study using
      Prokofiev's lesser known pedagogical work for the piano, which serves as an
      example of information gathering to apply toward a more effective method of
      instruction, which requires the teacher and student to exhaustively examine both
      composer and music in order to exact a more artistic, accurate performance. Much
      of the interpretation is based on Prokofiev's own thoughts as expressed in his
      personal memoirs and from his most distinguished music critics, many of whom were
      his peers during his lifetime, while some is taken from common sources, which are
      readily available to teacher and student. It is my belief that it is possible to
      divine extraordinary interpretations, information and outcomes from common
      sources. As the student and teacher gather information, it can be used to
      determine what should be included in a performance based not only on the
      composer's explicit directions, but also on implicit information that could lead
      to an inspired, original interpretation. It is written with the belief that music
      is more than the dots and lines on the page and that teaching and learning must
      be approached with that in mind. It is hoped that once teacher and student have
      completed this case study, the method will transfer to all future musical
      endeavors. 

PMID- 24455469
TI  - The relationship between transformational leadership and work engagement in
      governmental hospitals nurses: a survey study.
AB  - The aim of this study was to determine the effects of transformational leadership
      and its components on work engagement among hospital nurses. There are a few set
      of researches that have focused on the effects of transformational leadership on
      work engagement in nurses. A descriptive, correlational, cross-sectional design
      was used. In this study, 240 nurses have been chosen by stratified random
      sampling method which filled related self-reported scales include multifactor
      leadership questionnaire (MLQ) and work engagement scale. Data analysis has been
      exerted according to the statistical method of simple and multiple correlation
      coefficients. Findings indicated that the effect of this type of leadership on
      work engagement and its facets is positive and significant. In addition, the
      research illustrates that transformational leaders transfer their enthusiasm and
      high power to their subordinates by the way of modeling. This manner can increase
      the power as a component of work engagement in workers. Idealized influence among
      these leaders can result in forming a specific belief among employees toward
      those leaders and leaders can easily transmit their inspirational motivation to
      them. Consequently, it leads to make a positive vision by which, and by setting
      high standards, challenges the employees and establishes zeal along with optimism
      for attaining success in works. regarding to the results we will expand
      leadership and work engagement literature in hospital nurses. Also, we conclude
      with theoretical and practical implications and propose a clear horizon for
      future researches. 

PMID- 24455470
TI  - Stigmatization in teachers towards adults with attention deficit hyperactivity
      disorder.
AB  - OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is understood as a
      developmental disorder which shares common characteristics between childhood,
      adolescence and adulthood. However, ADHD is widely associated with misconceptions
      and misbeliefs which can lead to stigmatization. Teachers have an important role
      for the individual development as they accompany students for a long period of
      time. The aim of the present study was to explore stigmatizing attitudes in
      teachers towards adults with ADHD, thereby focusing on the developmental
      trajectory of the condition. Furthermore, it was aimed to identify factors
      contributing to prevention and intervention of stigmatization in ADHD. METHODS:
      Stigma responses of 170 teachers and 170 comparison participants were measured
      and compared with a recently developed tool for the assessment of stigmatization
      towards adults with ADHD. Furthermore, the contribution of knowledge about ADHD
      and the frequency of contact with adults with ADHD to stigmatization were
      explored. RESULTS: Teachers showed significantly less stigmatizing attitudes than
      comparison participants in various dimensions, including Reliability and Social
      Functioning, Malingering and Misuse of Medication and the total scale. With
      regard to teachers, frequency of contact with adults with ADHD was not related to
      stigma. However, knowledge about the disorder was negatively correlated with
      stigma in teachers, indicating lower expressed stigma with increasing knowledge
      about adult ADHD. CONCLUSIONS: Teachers demonstrated more sensitized attitudes
      towards stigma in adults with ADHD than comparison participants. Since the
      present results indicate that knowledge about ADHD increase the sensitivity
      towards the disorder, special education programs for the community may have the
      potential to reduce stigmatization towards adults with ADHD. Possibilities for
      intervention strategies of stigmatization in educational settings were discussed.

PMID- 24455471
TI  - Public assessment of key performance indicators of healthcare in a Canadian
      province: the effect of age and chronic health problems.
AB  - This study explores the effect of age and chronic conditions on public
      perceptions of the health system, as measured by the Key Performance Indicators
      (KPIs) of healthcare, in the province of Alberta in Canada. Drawing from data
      collected by Government of Alberta's Department of Health and Wellness, this
      research examines two key questions: (1) Do people in the 65+ age group rate the
      KPIs of healthcare (i.e., availability, accessibility, quality, outcome, and
      satisfaction) more favorably compared to people in younger age groups in Alberta?
      (2) Does the rating of KPIs of healthcare in Alberta vary with different chronic
      conditions (i.e., no chronic problem, chronic illnesses without pain, and chronic
      pain)? The findings indicate that people in the older age group tend to rate the
      KPIs of healthcare more favorably compared to younger age groups in Alberta, net
      of socio-demographic factors, self-reported health status, and knowledge and
      utilization of health services. However, people experiencing chronic pain are
      less likely to rate the KPIs of healthcare favorably compared to people with no
      chronic health problem in Alberta. Discussion includes implications of the
      findings for the healthcare system in the province. 

PMID- 24455472
TI  - Functional brain imaging studies of youth depression: a systematic review.
AB  - BACKGROUND: There is growing interest in understanding the neurobiology of major
      depressive disorder (MDD) in youth, particularly in the context of neuroimaging
      studies. This systematic review provides a timely comprehensive account of the
      available functional magnetic resonance imaging (fMRI) literature in youth MDD.
      METHODS: A literature search was conducted using PubMED, PsycINFO and Science
      Direct databases, to identify fMRI studies in younger and older youth with MDD,
      spanning 13-18 and 19-25 years of age, respectively. RESULTS: Twenty-eight
      studies focusing on 5 functional imaging domains were identified, namely emotion
      processing, cognitive control, affective cognition, reward processing and resting
      state functional connectivity. Elevated activity in "extended medial network"
      regions including the anterior cingulate, ventromedial and orbitofrontal
      cortices, as well as the amygdala was most consistently implicated across these
      five domains. For the most part, findings in younger adolescents did not differ
      from those in older youth; however a general comparison of findings in both
      groups compared to adults indicated differences in the domains of cognitive
      control and affective cognition. CONCLUSIONS: Youth MDD is characterized by
      abnormal activations in ventromedial frontal regions, the anterior cingulate and
      amygdala, which are broadly consistent with the implicated role of medial network
      regions in the pathophysiology of depression. Future longitudinal studies
      examining the effects of neurodevelopmental changes and pubertal maturation on
      brain systems implicated in youth MDD will provide a more comprehensive
      neurobiological model of youth depression.

PMID- 24455473
TI  - Ventral striatum gray matter density reduction in patients with schizophrenia and
      psychotic emotional dysregulation.
AB  - INTRODUCTION: Substantial heterogeneity remains across studies investigating
      changes in gray matter in schizophrenia. Differences in methodology,
      heterogeneous symptom patterns and symptom trajectories may contribute to
      inconsistent findings. To address this problem, we recently proposed to group
      patients by symptom dimensions, which map on the language, the limbic and the
      motor systems. The aim of the present study was to investigate whether patients
      with prevalent symptoms of emotional dysregulation would show structural neuronal
      abnormalities in the limbic system. METHOD: 43 right-handed medicated patients
      with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The
      patients and a control group of 34 healthy individuals underwent structural
      imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was
      compared between patient subgroups with different severity of emotional
      dysregulation. Group comparisons (comparison between patients with severe
      emotional dysregulation, patients with mild emotional dysregulation, patients
      with no emotional dysregulation and healthy controls) were performed using a one
      way ANOVA and ANCOVA respectively. RESULTS: Patients with severe emotional
      dysregulation had significantly decreased gray matter density in a large cluster
      including the right ventral striatum and the head of the caudate compared to
      patients without emotional dysregulation. Comparing patients with severe
      emotional dysregulation and healthy controls, several clusters of significant
      decreased GM density were detected in patients, including the right ventral
      striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral
      prefrontal and orbitofrontal cortex. The significant effect in the ventral
      striatum was lost when patients with and without emotional dysregulation were
      pooled and compared with controls. DISCUSSION: Decreased gray matter density in a
      large cluster including the right ventral striatum was associated with severe
      symptoms of emotional dysregulation in patients with schizophrenia. The ventral
      striatum is an important part of the limbic system, and was indicated to be
      involved in the generation of incentive salience and psychotic symptoms. Only
      patients with severe emotional dysregulation had decreased gray matter in several
      brain structures associated with emotion and reward processing compared to
      healthy controls. The results support the hypothesis that grouping patients
      according to specific clinical symptoms matched to the limbic system allows
      identifying patient subgroups with structural abnormalities in the limbic
      network.

PMID- 24455474
TI  - Altered network properties of the fronto-parietal network and the thalamus in
      impaired consciousness.
AB  - Recovery of consciousness has been associated with connectivity in the frontal
      cortex and parietal regions modulated by the thalamus. To examine this model and
      to relate alterations to deficits in cognitive functioning and conscious
      processing, we investigated topological network properties in patients with
      chronic disorders of consciousness recovered from coma. Resting state fMRI data
      of 34 patients with unresponsive wakefulness syndrome and 25 in minimally
      conscious state were compared to 28 healthy controls. We investigated global and
      local network characteristics. Additionally, behavioral measures were correlated
      with the local metrics of 28 regions within the fronto-parietal network and the
      thalamus. In chronic disorders of consciousness, modularity at the global level
      was reduced suggesting a disturbance in the optimal balance between segregation
      and integration. Moreover, network properties were altered in several regions
      which are associated with conscious processing (particularly, in medial parietal,
      and frontal regions, as well as in the thalamus). Between minimally conscious and
      unconscious patients the local efficiency of medial parietal regions differed.
      Alterations in the thalamus were particularly evident in non-conscious patients.
      Most of the regions affected in patients with impaired consciousness belong to
      the so-called 'rich club' of highly interconnected central nodes. Disturbances in
      their topological characteristics have severe impact on information integration
      and are reflected in deficits in cognitive functioning probably leading to a
      total breakdown of consciousness. 

PMID- 24455475
TI  - Insulin resistance and incident heart failure the ARIC study (Atherosclerosis
      Risk in Communities).
AB  - OBJECTIVES: This study was designed to assess the relationship between insulin
      resistance and incident heart failure (HF) in a community-based cohort.
      BACKGROUND: Diabetes mellitus increases the risk for HF, but the association
      between insulin resistance and HF in individuals without diabetes is unclear.
      METHODS: We prospectively analyzed 12,606 participants without diabetes mellitus,
      prevalent HF, or history of myocardial infarction at baseline (1987 to 1989) from
      the ARIC (Atherosclerosis Risk in Communities) study. We assessed the
      relationship between insulin resistance and incident HF using the homeostatic
      model assessment of insulin resistance (HOMA-IR) equation, adjusting for age,
      sex, race, body mass index, smoking, hypertension, center, and interim myocardial
      infarction. We tested for interactions by age, sex, obesity, and race. RESULTS:
      Participants with insulin resistance, defined as HOMA-IR >=2.5 (n = 4,810, 39%),
      were older, more likely female, African American, hypertensive, and had a higher
      body mass index as compared with those without insulin resistance. There were
      1,455 incident HF cases during a median of 20.6 years of follow-up. Insulin
      resistance defined by this threshold was not significantly associated with an
      increased risk for incident HF after adjustment (hazard ratio: 1.08, 95%
      confidence interval: 0.95 to 1.23). However, when analyzed continuously, this
      relationship was nonlinear, which indicated that risk increased, and was
      significantly associated with incident HF between HOMA-IR of 1.0 to 2.0,
      adjusting for baseline covariates; however, values over 2.5 were not associated
      with additional increased risk in adjusted models. CONCLUSIONS: In a community
      cohort, insulin resistance, defined by lower levels of HOMA-IR than previously
      considered, was associated with an increased risk for HF.

PMID- 24455477
TI  - Lysosomal storage diseases: heterogeneous group of disorders.
AB  - The name of lysosomal storage diseases stems from the fact that in this category
      of disorders specific undegraded materials are stored in the lysosomes. This is
      usually caused by a lysosomal enzyme deficiency and leads to a cascade of
      pathological outcomes. Apart from deficiency of lysosomal enzymes, lysosomal
      storage diseases also include deficiencies in proteins necessary for enzyme
      functioning, proteins needed for post-translational modification of these enzymes
      and proteins required for export of certain compounds from the lysosomes. 

PMID- 24455479
TI  - Influencing Factors on Reproducibility and Stability of MRI NIPAM Polymer Gel
      Dosimeter.
AB  - INTRODUCTION: At present, the polymer gel dosimeter is considered to be the best
      possible dosimeter for measuring 3-dimesional radiation dose distribution in
      radiotherapy. These gels are normally toxic; therefore, manufacturing, handling
      and discarding them require special attention. In order to find less toxic
      recipe, N-isopropyle acrylamide polymer gel (NIPAM) was introduced. In this
      study, the reproducibility and stability of NIPAM polymer gel dose response
      together with some influencing factors related to MR imaging were studied.
      METHODS: The NIPAM gel was prepared according to a method, described by senden et
      al in 2006. The gels were irradiated approximately 2 h after manufacturing and MR
      images of the gel were made 24 h after irradiation. The effects of different
      batches, post-irradiation time and the MRI room temperature on reproducibility
      and stability of polymer gel dose response were explored by analyzing the NMR
      response (R2) of the gel. RESULTS: : In a fixed temperature, the response of the
      gel was found to be stable 24 h after irradiation. The results showed that the
      dose response of the NIPAM polymer gel is highly reproducible in the same and
      different batches of chemical. No inhomogeneity was observed for magnetic fields
      in the specified position of measurements and 5 degrees C fluctuation was
      recorded for MRI room temperature. CONCLUSION: Fluctuation in MRI room
      temperature necessitates that stringent attention to be paid to controlling the
      gel temperature at the time of imaging. The new formulation of polymer gel
      ensures stability of the gels' spatial resolution and makes it a suitable
      dosimeter for distant or remote measurements.

PMID- 24455478
TI  - Dysregulated pH in Tumor Microenvironment Checkmates Cancer Therapy.
AB  - INTRODUCTION: The dysregulation of pH by cancerous cells of solid tumors is able
      to create a unique milieu that is in favor of progression, invasion and
      metastasis as well as chemo-/immuno-resistance traits of solid tumors.
      Bioelements involved in pH dysregulation provide new set of oncotargets,
      inhibition of which may result in better clinical outcome. METHODS: To study the
      impacts of pH dysregulation, we investigated the tumor development and
      progression in relation with Warburg effect, glycolysis and formation of aberrant
      tumor microenvironment. RESULTS: The upregulation of glucose transporter GLUT-1
      and several enzymes involve in glycolysis exacerbates this phenomenon. The
      accumulation of lactic acids in cancer cells provokes upregulation of several
      transport machineries (MCT-1, NHE-1, CA IX and H(+) pump V-ATPase) resulting in
      reinforced efflux of proton into extracellular fluid. This deviant event makes pH
      to be settled at 7.4 and 6.6 respectively in cancer cells cytoplasm and
      extracellular fluid within the tumor microenvironment, which in return triggers
      secretion of lysosomal components (various enzymes in acidic milieu with pH 5)
      into cytoplasm. All these anomalous phenomena make tumor microenvironment (TME)
      to be exposed to cocktail of various enzymes with acidic pH, upon which
      extracellular matrix (ECM) can be remodeled and even deformed, resulting in
      emergence of a complex viscose TME with high interstitial fluid pressure.
      CONCLUSION: It seems that pH dysregulation is able to remodel various physiologic
      functions and make solid tumors to become much more invasive and metastatic. It
      also can cause undesired resistance to chemotherapy and immunotherapy. Hence,
      cancer therapy needs to be reinforced using specific inhibitors of bioelements
      involved in pH dysregulation of TME in solid tumors.

PMID- 24455480
TI  - Involvement of 5HT3 Receptors in Anti-Inflammatory Effects of Tropisetron on
      Experimental TNBS-Induced Colitis in Rat.
AB  - INTRODUCTION: There is a pressing need for research leading to the development of
      new effective drugs with lower side effects and more efficacy for treating
      inflammatory bowel disease (IBD). The analgesic and anti-inflammatory properties
      of 5-Hydroxytryptamine (5-HT)-3 receptor antagonists have been shown in in vivo
      and in vitro studies. The present study was designed to investigate the effects
      of tropisetron, a 5-HT3 receptor antagonist, on an immune-based animal model of
      IBD. METHODS: In the present study, the trinitrobenzenesulfonic acid (TNBS) model
      of colitis in the rat was used. Two hours after induction of colitis in rats,
      tropisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide
      (mCPBG, 5 mg/kg), a 5-HT3 receptor agonist, or tropisetron + mCPBG were
      intraperitoneally (i.p.) administrated for 6 days. Animals were then sacrificed;
      macroscopic, histological, biochemical (myeloperoxidase [MPO]) assessments and
      ELISA test (tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta)
      were performed on distal colon samples. RESULTS: Tropisetron or dexamethasone
      treatment significantly reduced macroscopic and microscopic colonic damages. In
      addition, a significant reduction in MPO activity and colonic levels of
      inflammatory cytokines was seen. The beneficial effects of tropisetron were
      antagonized by concurrent administration of mCPBG. CONCLUSION: The present study
      indicates that the protective effects of tropisetron on TNBS-induced colitis can
      be mediated by 5-HT3 receptors.

PMID- 24455476
TI  - Redox regulation of mitochondrial function with emphasis on cysteine oxidation
      reactions.
AB  - Mitochondria have a myriad of essential functions including metabolism and
      apoptosis. These chief functions are reliant on electron transfer reactions and
      the production of ATP and reactive oxygen species (ROS). The production of ATP
      and ROS are intimately linked to the electron transport chain (ETC). Electrons
      from nutrients are passed through the ETC via a series of acceptor and donor
      molecules to the terminal electron acceptor molecular oxygen (O2) which
      ultimately drives the synthesis of ATP. Electron transfer through the respiratory
      chain and nutrient oxidation also produces ROS. At high enough concentrations ROS
      can activate mitochondrial apoptotic machinery which ultimately leads to cell
      death. However, if maintained at low enough concentrations ROS can serve as
      important signaling molecules. Various regulatory mechanisms converge upon
      mitochondria to modulate ATP synthesis and ROS production. Given that
      mitochondrial function depends on redox reactions, it is important to consider
      how redox signals modulate mitochondrial processes. Here, we provide the first
      comprehensive review on how redox signals mediated through cysteine oxidation,
      namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S
      nitrosylation, regulate key mitochondrial functions including nutrient oxidation,
      oxidative phosphorylation, ROS production, mitochondrial permeability transition
      (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the
      chemistry behind these reactions and how they are modulated in mitochondria. In
      addition, we also discuss emerging knowledge on disorders and disease states that
      are associated with deregulated redox signaling in mitochondria and how
      mitochondria-targeted medicines can be utilized to restore mitochondrial redox
      signaling. 

PMID- 24455481
TI  - Virtual screening of m3 protein antagonists for finding a model to study the
      gammaherpesvirus damaged immune system and chemokine related diseases.
AB  - INTRODUCTION: M3 protein is a chemokine decoy receptor involved in pathogenesis
      of persistent infection with gammaherpesvirus and complications related to the
      latency of this pathogen. We proposed that antagonists of the M3 would provide a
      unique opportunity for studying new therapeutic strategies in disordered immune
      system, immune-deficient states and role of chemokines in pathogenesis
      development. METHODS: Comparative modeling and fold recognition algorithms have
      been used for prediction of M3 protein 3-D model. Evaluation of the models using
      Q-mean and ProSA-web score, has led to choosing predicted model by fold
      recognition algorithm as the best model which was minimized regarding energy
      level using Molegro Virtual Docker 2011.4.3.0 (MVD) software. Pockets and active
      sites of model were recognized using MVD cavity detection, and MetaPocket
      algorithms. Ten thousand compounds accessible on KEGG database were screened; MVD
      was used for computer simulated docking study; MolDock SE was selected as docking
      scoring function and final results were evaluated based on MolDock and Re-rank
      score. RESULTS: Docking data suggested that prilocaine, which is generally
      applied as a topical anesthetic, binds strongly to 3-D model of M3 protein.
      CONCLUSION: This study proposes that prilocaine is a potential inhibitor of M3
      protein and possibly has immune enhancing properties.

PMID- 24455482
TI  - Colorimetric Assay for Exon 7 SMN1/SMN2 Single Nucleotide Polymorphism Using Gold
      Nanoprobes.
AB  - INTRODUCTION: Proximal spinal muscular atrophy (SMA) is one of the most
      significant neurodegenerative diseases amongst the autosomal-recessive genetic
      disorders which is caused by the absence of protein survival of motor neuron
      (SMN). A critical nucleotide difference in SMN2 compared to SMN1 gene leads to an
      inefficient protein. Hence, homozygous lack of SMN1 provides a progressive
      disease. Due to the high prevalence, up to now, several molecular diagnostic
      methods have been used which most of them are lengthy, expensive, and laborious.
      METHODS: In the present study, we exploited a gold nanoprobe-based method for
      semi-quantitative SMN1 gene dosage analysis compared to SMN2. The assay was done
      under hybridization process between Au nanoprobes and different ratios of
      SMN1/SMN2 amplicons. RESULTS: UV-vis spectra indicated that after the salt
      addition, nanoprobes aggregated gradually and their peak shifted to longer
      wavelengths except in the stable target-nanoprobes hybridization. The results
      revealed that the homozygous genotype of SMN2 gene is distinguished from the
      heterozygous genotypes of SMN genes by the naked eye, whereas different ratio of
      heterozygous genotypes (SMN1/SMN2) are differentiated better from each other
      using peak analysis ratios. CONCLUSION: The presented strategy is an alternative
      simple method for discrimination of homozygous deletion of SMN1 in less than 30
      min. However, further evaluation of the assay using clinical samples is
      recommended prior to real-world use.

PMID- 24455483
TI  - Evaluating the antimicrobial activity of methonolic extract of rhus succedanea
      leaf gall.
AB  - INTRODUCTION: The worldwide increased bacterial resistance to antibiotics and the
      undesirable side effects associated with constant use of synthetic drugs has
      prompted the search for novel antimicrobial agents, particularly those
      manufactured from plants. This study is designed to ascertain the antibacterial
      potential of Rhus succedanea leaf gall extracts on the growth of gram-positive
      and gram-negative bacteria. METHODS: The methanolic and hexane extract of
      different concentrations (100, 250, and 500 MUg/ml) were prepared and their
      antibacterial efficacy was tested against clinical isolates of Escherichia coli,
      Salmonella typhi, Micrococcus luteus, and Staphylococcus aureus using agar well
      diffusion method and the size of inhibition zone was measured in millimeters.
      RESULTS: The methanol and hexane extracts differed significantly in their
      antimicrobial activity with methanol extract showing a potent inhibitory activity
      in the range of 16+/-2 to 23+/-1, which was almost equal to the values of
      ciprofloxacin (25+/-3), used as a standard. Further, the methanol extract was
      mostly potent and effective in inhibiting the growth of gram-negative bacteria,
      namely, E. coli, when compared to gram -positive bacteria stains, which are
      responsible for antimicrobial activities. The phytochemical screening showed
      positive results for the presence of steroids, triterpenes, alkaloids, and
      carbohydrates. CONCLUSION: The potent antibacterial activity of Rhus succedanea
      leaf gall extracts indicates its useful therapeutic application against bacterial
      infection. Furthermore, this study indicates that the extract might be exploited
      as natural drug for the treatment of infectious diseases and could be useful in
      understanding the relations between traditional cures and current medications.

PMID- 24455484
TI  - Commentary on: Serum Albumin for Tuberculosis in HIV Infected Patients Eligible
      for Antiretroviral Therapy.

PMID- 24455485
TI  - Authors' reply: Serum Albumin for Tuberculosis in HIV Infected Patients Eligible
      for Antiretroviral Therapy.

PMID- 24455487
TI  - Comparison of antibody responses to human papillomavirus vaccination as measured
      by three assays.
AB  - BACKGROUND: Different assays, including the competitive Luminex immunoassay
      (cLIA), secreted alkaline phosphatase neutralization assay (SEAP-NA), and virus
      like particle-based ELISA, are commonly used to measure antibody responses after
      human papillomavirus (HPV) vaccination. Direct assay comparisons aid
      interpretation of immunogenicity data evaluated by different assays. METHODS: We
      compared cLIA to SEAP-NA and ELISA among 51 HPV16/18-vaccinated women enrolled in
      the Costa Rica Vaccine Trial. We tested replicate serum samples collected at
      months 0, 1, and 12 by HPV16/18 cLIA, SEAP-NA, and ELISA. For a subset (N = 10),
      we further tested month 6, 24 and 36 samples. We calculated seroprevalence
      estimates and Spearman rank correlation coefficients comparing cLIA to SEAP-NA
      and ELISA. RESULTS: After one vaccine dose, seroprevalence by SEAP-NA and ELISA
      was 100% (both HPV16 and HPV18), and by cLIA was 96% (95% CI 87-100%) for HPV16
      and 71% (95% CI 56-83%) for HPV18. Seroprevalence was 100% by all assays after
      three doses. Correlation between assays was high after one vaccine dose
      [cLIA/SEAP-NA rho = 0.91 (HPV16) and rho = 0.86 (HPV18); cLIA/ELISA rho = 0.84
      (HPV16) and rho = 0.74 (HPV18); all p < 0.001] and remained high through month
      36. Ratios of mean antibody levels to seropositivity cutoffs at month 36 were
      lower for cLIA than for SEAP-NA or ELISA, particularly for HPV18 (HPV18 ratio for
      cLIA 1.9, SEAP-NA 3.5, ELISA 3.4). CONCLUSION: Though correlation between cLIA
      and SEAP-NA/ELISA is high and stable after vaccination, the assays differ in
      scale and sensitivity, with notable differences after one vaccine dose and for
      HPV18. Our results demonstrate that comparisons of antibody responses to HPV
      vaccination measured by different assays are approximate, and must consider
      biological and technical differences between assays.

PMID- 24455486
TI  - Serglycin: at the crossroad of inflammation and malignancy.
AB  - Serglycin has been initially characterized as an intracellular proteoglycan
      expressed by hematopoietic cells. All inflammatory cells highly synthesize
      serglycin and store it in granules, where it interacts with numerous inflammatory
      mediators, such as proteases, chemokines, cytokines, and growth factors.
      Serglycin is implicated in their storage into the granules and their protection
      since they are secreted as complexes and delivered to their targets after
      secretion. During the last decade, numerous studies have demonstrated that
      serglycin is also synthesized by various non-hematopoietic cell types. It has
      been shown that serglycin is highly expressed by tumor cells and promotes their
      aggressive phenotype and confers resistance against drugs and complement system
      attack. Apart from its direct beneficial role to tumor cells, serglycin may
      promote the inflammatory process in the tumor cell microenvironment thus
      enhancing tumor development. In the present review, we discuss the role of
      serglycin in inflammation and tumor progression. 

PMID- 24455488
TI  - Radiotherapy for thymic carcinoma: adjuvant, inductive, and definitive.
AB  - Although historically thymoma and thymic carcinoma have been treated surgically,
      radiation therapy also has an important role, either as postoperative therapy to
      reduce the risk of mediastinal recurrence or as part of definitive treatment for
      patients who cannot undergo surgery. Induction chemotherapy and molecular
      targeted agents may also be appropriate for thymic carcinoma, the behavior of
      which resembles non-small-cell lung carcinoma more than that of thymoma or
      invasive thymoma and is increasingly being treated like lung cancer. We present
      here a review of current therapies for thymic malignancies and briefly discuss
      the potential benefits from novel technologies for such treatment. 

PMID- 24455489
TI  - Evidence That GRIN2A Mutations in Melanoma Correlate with Decreased Survival.
AB  - Previous whole-exome sequencing has demonstrated that melanoma tumors harbor
      mutations in the GRIN2A gene. GRIN2A encodes the regulatory GluN2A subunit of the
      glutamate-gated N-methyl-d-aspartate receptor (NMDAR), involvement of which in
      melanoma remains undefined. Here, we sequenced coding exons of GRIN2A in 19 low
      passage melanoma cell lines derived from patients with metastatic melanoma.
      Potential mutation impact was evaluated in silico, including within the GluN2A
      crystal structure, and clinical correlations were sought. We found that of 19
      metastatic melanoma tumors, four (21%) carried five missense mutations in the
      evolutionarily conserved domains of GRIN2A; two were previously reported.
      Melanoma cells that carried these mutations were treatment-naive. Sorting
      intolerant from tolerant analysis predicted that S349F, G762E, and P1132L would
      disrupt protein function. When modeled into the crystal structure of GluN2A,
      G762E was seen to potentially alter GluN1-GluN2A interactions and ligand binding,
      implying disruption to NMDAR functionality. Patients whose tumors carried non
      synonymous GRIN2A mutations had faster disease progression and shorter overall
      survival (P < 0.05). This was in contrast to the BRAF V600E mutation, found in
      58% of tumors but showing no correlation with clinical outcome (P = 0.963).
      Although numbers of patients in this study are small, and firm conclusions about
      the association between GRIN2A mutations and poor clinical outcome cannot be
      drawn, our results highlight the high prevalence of GRIN2A mutations in
      metastatic melanoma and suggest for the first time that mutated NMDARs impact
      melanoma progression. 

PMID- 24455493
TI  - Clinical research involving minors in international and serbian regulations.
AB  - BACKGROUND: Participation in clinical trials can be useful for the health of a
      person, in who it is conducted, but it does not have to be - it can even be
      harmful. Therefore, primary motive to accept such risk is humanity and human wish
      to contribute to the progress of medicine; this is expressed by personal consent.
      The consent, however, can be an expression of personal humanity, and for this, it
      is not logical that someone can give consent on behalf of someone else, as it is
      done by a legally authorized representative on behalf of a minor. Therefore,
      authors raise 3 questions: What are the reasons to consider representative's
      consent acceptable? How should a model of regulations look like in order to
      provide the most complete possible protection to a minor? Is actual regulation of
      minors' position within international and Serbian law, analyzed here by authors
      for their specific solutions, acceptable? Representative's consent is acceptable
      only for therapeutic research, because these can bring benefits to everyone's
      health, including a minor in which those are conducted - this is an acceptable
      (secondary) motive of participation in the research. Expression of humanity on
      other's behalf, typical for non-therapeutic research, is not acceptable; this
      makes ban of minors' participation in non-therapeutic research more appropriate
      regulation model. International regulations are not in accordance to results
      presented in the paper for allowing participation of minors both in therapeutic
      and non-therapeutic research. Serbian regulation is closer to the most acceptable
      regulation model.

PMID- 24455494
TI  - On the Effectiveness of Primary Health Care System in Controlling HIV/AIDS in
      Iran.

PMID- 24455492
TI  - Impact of pneumococcal vaccines use on invasive pneumococcal disease in Nunavik
      (Quebec) from 1997 to 2010.
AB  - BACKGROUND: In 2000, an outbreak of severe pneumonia caused by a virulent clone
      of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of
      Quebec. A mass immunization campaign was implemented in the spring of 2002,
      targeting persons >=5 years of age and using the 23-valent pneumococcal
      polysaccharide vaccine (PPSV23). At the same time, the 7-valent pneumococcal
      conjugate vaccine (PCV7) was introduced into the routine immunization programme
      of infants, with catch-up for children up to 4 years of age. OBJECTIVES: To
      describe the epidemiology of invasive pneumococcal disease (IPD) in relation to
      PPSV23 and PCV7 use. STUDY DESIGN AND METHODS: Retrospective analysis of IPD
      cases identified by the Quebec public health laboratory during the period 1997
      2010. RESULTS: A total of 82 IPD cases were identified during the study period.
      In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign
      but breakthrough cases continued to occur. Following PCV7 use in children, there
      was a decrease in the incidence of vaccine-type IPD and replacement by other
      serotypes in adults. In children, a marked decrease in the annual incidence of
      serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000
      in 1997-2001 vs. 10/100,000 in 2004-2010 (p<0.01). Concomitantly, the incidence
      of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to
      109/100,000 (p=0.11). CONCLUSION: The mass immunization campaign using the PPSV23
      in 2002 and the introduction of PCV7 for the routine immunization of infants
      induced important modifications in the epidemiology of IPD. IPD rates in Nunavik
      remain much higher than in the southern part of the province both in children and
      adults. More effective pneumococcal vaccines are needed to eliminate geographic
      disparities in IPD risk.

PMID- 24455491
TI  - Role of DUOX in gut inflammation: lessons from Drosophila model of gut-microbiota
      interactions.
AB  - It is well-known that certain bacterial species can colonize the gut epithelium
      and induce inflammation in the mucosa, whereas other species are either benign or
      beneficial to the host. Deregulation of the gut-microbe interactions may lead to
      a pathogenic condition in the host, such as chronic inflammation, tissue
      injuries, and even cancer. However, our current understanding of the molecular
      mechanisms that underlie gut-microbe homeostasis and pathogenesis remains
      limited. Recent studies have used Drosophila as a genetic model to provide novel
      insights into the causes and consequences of bacterial-induced colitis in the
      intestinal mucosa. The present review discusses the interactions that occur
      between gut-associated bacteria and host gut immunity, particularly the bacterial
      induced intestinal dual oxidase (DUOX) system. Several lines of evidence showed
      that the bacterial-modulated DUOX system is involved in microbial clearance,
      intestinal epithelial cell renewal (ECR), redox-dependent modulation of signaling
      pathways, cross-linking of biomolecules, and discrimination between symbionts and
      pathogens. Further genetic studies on the Drosophila DUOX system and on gut
      associated bacteria with a distinct ability to activate DUOX may provide critical
      information related to the homeostatic inflammation as well as etiology of
      chronic inflammatory diseases, which will enhance our understanding on the
      mucosal inflammatory diseases frequently observed in the microbe-contacting
      epithelia of humans. 

PMID- 24455490
TI  - Manipulation of intestinal epithelial cell function by the cell contact-dependent
      type III secretion systems of Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus elicits gastroenteritis by deploying Type III Secretion
      Systems (TTSS) to deliver effector proteins into epithelial cells of the human
      intestinal tract. The bacteria must adhere to the human cells to allow
      colonization and operation of the TTSS translocation apparatus bridging the
      bacterium and the host cell. This article first reviews recent advances in
      identifying the molecules responsible for intercellular adherence. V.
      parahaemolyticus possesses two TTSS, each of which delivers an exclusive set of
      effectors and mediates unique effects on the host cell. TTSS effectors primarily
      target and alter the activation status of host cell signaling proteins, thereby
      bringing about changes in the regulation of cellular behavior. TTSS1 is
      responsible for the cytotoxicity of V. parahaemolyticus, while TTSS2 is necessary
      for the enterotoxicity of the pathogen. Recent publications have elucidated the
      function of several TTSS effectors and their importance in the virulence of the
      bacterium. This review will explore the ability of the TTSS to manipulate
      activities of human intestinal cells and how this modification of cell function
      favors bacterial colonization and persistence of V. parahaemolyticus in the host.

PMID- 24455495
TI  - The Concept of Liver Disease Diagnosis in Avicenna's Canon of Medicine.

PMID- 24455496
TI  - Avicenna aspect of cardiac risk factors.

PMID- 24455497
TI  - Avicenna and oral lithotripters.

PMID- 24455498
TI  - Public health surveillance and hajj pilgrimage as a mass gathering.

PMID- 24455499
TI  - Impact of Emotional Intelligence towards Leadership among IT/ITES employees in
      Coimbatore Region.

PMID- 24455500
TI  - A fresh look at oncology facts on south central Asia and SAARC countries.

PMID- 24455501
TI  - Oncology in Nepal.
AB  - Nepal being a developing country is lagging behind in almost all its healthcare
      services and hence Oncology is also in its primitive stages. In this review,
      effort is being made to outline the historical perspectives regarding evolution
      of Oncology in Nepal, with a brief overview of cancer scenario in the country.
      This review also highlights the challenges, constraints and successes that are
      associated in initiation and nurturing of Oncology in developing countries. It
      also emphasizes the history, current status, challenges of academic training in
      oncology and also portrays the effort of various national and international
      organisations and government trying to achieve recent advancements and expensive
      modern technology. 

PMID- 24455502
TI  - Importance of dose intensity in treatment of advanced non-small cell lung cancer
      in the elderly.
AB  - Maintaining appropriate dose intensity is important not only in the curative
      setting but also in treatment with palliative intent. We evaluated the outcome of
      advanced non small cell lung cancer treated with doublet platinum based
      chemotherapy. Outcome was compared between patients treated by medical
      oncologists at a tertiary cancer center and those treated by non medical
      oncologists in the community. The dose intensity, overall response rate and
      overall survival was significantly better when patients were treated by trained
      qualified and experienced medical oncologists. Hence, even in the palliative
      setting, cancer directed systemic therapy will yield maximum benefit for the
      patients when treated by medical oncologists. 

PMID- 24455503
TI  - Chronic myeloid leukemia: In pursuit of perfection.
AB  - The resounding success of imatinib (IM) as front line treatment in patients with
      chronic myeloid leukemia (CML) has certainly made a paradigm shift in the
      therapeutic algorithm of this disorder. The precise targeting of the BCR-ABL
      oncogene in CML has entitled it to be the poster child of translational medicine
      with a well-deserved Oscar ovation from the oncology community. Clinicians are
      now empowered with first-, second- and third-generation tyrosine kinases, as well
      as advanced molecular tools to monitor disease and characterize resistance. We
      have come a long way in successfully managing these patients, but there are still
      a significant few unmet clinical needs which need addressing and targeting to
      optimize clinical outcomes. This review focuses on 4 such pertinent and relevant
      clinical issues, which still need ironing out to fulfill our ambition of
      achieving 'perfection' in this patient cohort. 

PMID- 24455504
TI  - Chronic myelogenous leukemia in Libya.

PMID- 24455505
TI  - Skin markings methods and guidelines: A reality in image guidance radiotherapy
      era.
AB  - Preparation of site of radiation delivery is an important process in radiation
      treatment planning and plays a crucial role during a course of radiotherapy to
      achieve reproducibility of set-up and accuracy of treatment delivery. The
      preparation of treatment area is done by markings of field center, field edge or
      other reference point of planned field. Both non-invasive (marker pen, henna) and
      invasive methods (tattoo) are available for marking with limitations of each.
      Tattoo with a needle pricked at angle of 30 degrees  to 1-2 mm depth to create
      tattoo 2-3 mm diameter in size is an ideal procedure. Visibility, permanent
      nature, social-religious belief, and mobility of skin are one of the main
      concerns about tattoo. Tattoo removal can be done performed if desirable by
      patients by various modern ways, which will be esthetically available.
      Dermabrasion, cryotherapy, surgery, QSRL (Q-switched ruby laser) are common
      methods of tattoo removal. Esthetic dissatisfaction, allergy, dermatoses,
      keloids, infection, fanning/fading of tattoo are associated problems. In IMRT and
      IGRT treatment, delivery dependence on tattoo in reduced and use of surrogate
      markers including particularly for bony set-up and implanted markers (e.g. gold
      seeds) for tumor localization and treatment verification is increasing. However,
      these are complex procedures and require an expertise. Ease of set-up and less
      time required for tattooing are one of the main advantages of tattoo as compared
      to external or internal marker set-up. Tattoo still remains a crucial method of
      positioning, especially in developing countries and in palliative treatment
      settings. 

PMID- 24455506
TI  - Metastatic renal cell carcinoma: Current scenario and future trends.
AB  - An improved understanding of the biology of renal cell carcinoma (RCC) has led to
      the development of a number of targeted agents, which has resulted in a paradigm
      shift in the management of metastatic RCC. We review the current therapeutic
      strategies for metastatic RCC and present a synopsis of the novel agents in use
      today with a discussion of the phase III trials that demonstrated their clinical
      benefit. The management of RCC continues to evolve. The introduction of VEGF and
      mTOR inhibitors has markedly expanded our drug armamentarium and improved the
      outcome of a disease that has always been challenging to treat. Knowledge from
      upcoming trials will help us utilize these drugs for maximum clinical efficacy
      with optimal dosing and sequencing, either individually or in combination
      therapy. 

PMID- 24455507
TI  - Pulmonary tuberculosis as differential diagnosis of lung cancer.
AB  - Patients with lung cancer are often misdiagnosed as pulmonary tuberculosis
      leading to delay in the correct diagnosis as well as exposure to inappropriate
      medication. Several factors are responsible for this situation in developing
      countries, including lack of awareness, inadequate infrastructure and socio
      economic factors. This article outlines the differences between the two diseases
      as well as features that would make a clinician suspect the right diagnosis
      early. 

PMID- 24455508
TI  - Thyroid cancer in Gardner's syndrome: Case report and review of literature.
AB  - Gardner's syndrome is a variant of familial adenomatous polyposis. A multitude of
      extra-colonic manifestations including various endocrine tumors have been
      associated with this syndrome, the commonest of which is thyroid cancer. Majority
      of the patients with thyroid cancer and Gardner's syndrome are females. Here we
      describe a male patient with Gardner's syndrome who subsequently developed
      thyroid cancer. 

PMID- 24455509
TI  - A Call to action: For the attention of oncologists!

PMID- 24455510
TI  - A call to action by Dr. Abdul Ghafur, Apollo Hospital, Chennai.

PMID- 24455511
TI  - The changing landscape of hormonal therapy in castration-resistant prostate
      cancer.

PMID- 24455512
TI  - Using p53 to help diagnose ovarian cancer.

PMID- 24455513
TI  - The changing landscape of cancer in rural setting.

PMID- 24455514
TI  - A cytohistological study of p53 overexpression in ovarian neoplasms.
AB  - BACKGROUND: The present study was undertaken to evaluate the diagnostic accuracy
      of imprint cytology in ovarian neoplasms, investigate the biological significance
      of p53 expression in malignant ovarian tumors and correlate it with histological
      type, grade and stage of tumor. MATERIAL AND METHODS: A total of 50 cases
      including 25 prospective and 25 retrospective cases were studied. Imprint
      cytology was performed on 25 ovarian tumors and compared with histopathological
      diagnosis. p53 immunohistochemistry was performed on all 50 cases. RESULTS: On
      immunohistochemistry, all the benign tumors were negative for p53 while 42% of
      primary ovarian malignant tumors were positive. p53 expression was found to have
      a diagnostic value in differentiating benign from malignant tumors. p53
      overexpression did not show any significant correlation with prognostic factors
      as stage of disease, grade of differentiation and type of tumor. CONCLUSION: The
      present study confirms the importance of p53 tumor suppressor gene expression as
      documented by immunohistochemistry in the differentiation of malignant and benign
      ovarian tumors.

PMID- 24455515
TI  - The scenario of presentation of young females in a rural cancer hospital of North
      India: An initial experience.
AB  - A total of 51 cases of young females aged between 18-35 years were prospectively
      studied for the presentation in a Rural Charitable Cancer hospital in north India
      during the period August 2011 to April 2012. Breast related symptoms comprised 27
      (52.94%) cases, out of which 10 (19.60%) were proven malignant. Other cases seen
      were Gynecological (Gyn) 8 (15.68%), Head and Neck (H and N) 5 (9.80%),
      Gastrointestinal (GI) 4 (7.84%), Lymphomas 3 (5.88%) and 2 (3.92%) cases each of
      Bone Tumors and Central Nervous System (CNS) tumors. Breast related symptoms
      constituted the major presentation in young females (aged 18-35 years) in our
      Rural Cancer Hospital. This high percentage of Breast related symptoms points
      towards the increasing trend of Breast malignancies possibly overtaking cancer
      cervix in rural India, as already in the urban settlements of India as well as
      the increasing awareness in the females of rural India regarding early symptoms
      of carcinoma Breast. 

PMID- 24455516
TI  - The role of honey in healing of bedsores in cancer patients.
AB  - BACKGROUND: Honey was used to treat infected wounds as long as 2000 years before
      bacteria were discovered. It has been reported to have inhibitory action to
      around 50 species of bacteria and fungi (aspergillus, penicillium). Usually,
      Metronidazole powder is used in our palliative clinic for wound healing due to
      low cost & effectivity. Honey is cheap, easily available ingredient with high
      astringent activity. OBJECTIVE: Objectives of the study were to find out the
      effectiveness of Honey in terms of rate of wound healing & pain control in
      bedsores of cancer patients. MATERIALS AND METHODS: 40 cancer patients with
      bedsore wounds were randomly assigned (1:1 ratio i.e. 20 in each arm) for Study
      Arm (Honey plus Metronidazole powder) and Control Arm (only Metronidazole
      powder), attending Palliative clinic of our department in between July 2010 to
      September 2011.Washing of the wound with normal saline done daily before
      application of above medicaments. Change of posture & soft bed were encouraged in
      both groups. A pre designed interview proforma, standardised Bates Jensen Wound
      Assessment Tool and Visual Analogue Pain assessment scale were used to collect
      and assess data. RESULTS: There was significant difference in wound healing
      status (F value = 6.523; Critical Difference =14.03, P>0.05) from day 10 and pain
      reduction also (F value = 6.638 and Critical Difference = 1.667, P>0.05) from day
      7 in study arm. CONCLUSION: Application of honey dressing provides a better wound
      healing, rapid pain relief in cancer patients with bedsores in palliative
      settings.

PMID- 24455517
TI  - Post-chemotherapy arthralgia and arthritis in lung cancer.
AB  - OBJECTIVE: Evaluate the characteristics of arthritis, arthralgia and
      musculoskeletal pain after chemotherapy in patients with lung cancer. MATERIALS
      AND METHODS: In this study, we evaluate the characteristics of 17 patients with
      joint symptoms following receiving chemotherapy for lung cancer. Demographic
      information of patients including sex, age, time of rheumatologic findings after
      starting of chemotherapy, time of improvement after starting of medication, and
      relevant laboratory findings for each patient. RESULTS: A total of seventeen
      patients (six women with mean age 41.2 +/- 5.2 years and 11 men with mean age
      42.5 +/- 8.2) that received standard chemotherapy for lung cancer according to
      stage of disease. Joint symptoms usually began about seven months after the first
      session of chemotherapy. Patients had an average of two tender joints and 1 hr of
      morning stiffness. Four patients were positive for anti-nuclear antibody, and
      none of patient was positive for rheumatoid factor. Non-steroidal anti
      inflammatory drugs, disease modifying anti-rheumatic drugs (DMARD),
      corticosteroids, and venlafaxine were prescribed. Four patients did not show an
      improvement. Follow-up was available for all patients. 11 patients showed
      favorable responses, characterized by a significant decrease (more than 50%) in
      morning stiffness, pain, and tender joint counts after a mean of three months'
      treatment. Two patients had complete resolution of symptoms and did not required
      further medications for arthritis, arthralgia or musculoskeletal pain.
      CONCLUSION: Chemotherapy-related arthropathy in lung cancer is not uncommon.
      Early treatment with NSAID, DMARD, and corticosteroids is effective in the
      majority of patients.

PMID- 24455518
TI  - Fluoride levels and osteosarcoma.
AB  - CONTEXT: Osteosarcoma is a rare malignant bone tumor, commonly occurring in the
      age group of 10 to 24 years. Recent reports have indicated that there is a link
      between fluoride exposure and osteosarcoma. AIMS: The present study was planned
      to analyze serum levels of fluoride in patients of osteosarcoma and fluoride
      content of their drinking water. SETTINGS AND DESIGN: The present study was
      carried out comparing 10 patients of osteosarcoma and 10 healthy volunteers (who
      served as controls). MATERIALS AND METHODS: Serum and drinking water fluoride
      levels were estimated by ion selective electrode. STATISTICAL ANALYSIS USED: The
      data were computed as mean +/- SD and Student's t test was applied. RESULTS:
      Both, the serum and drinking water fluoride levels, were significant by higher in
      patients with osteosarcoma as compared to controls (P > 0.05, P > 0.001,
      respectively). CONCLUSIONS: These results suggest a link between fluoride
      exposure and osteosarcoma.

PMID- 24455519
TI  - Role of bacteria in oral carcinogenesis.
AB  - Oral cancer is the most common cancer diagnosed in Indian men and is the leading
      cause of cancer deaths. It is considered as a multistep and multifactorial
      disease. Besides accumulation of genetic mutations, numerous other carcinogens
      are involved. In this category, viral and chemical carcinogens are well studied
      and documented. However, in the oral cavity, the role of microbiota in
      carcinogenesis is not known. Microbial populations on mouth mucosa differ between
      healthy and malignant sites, and certain oral bacterial species have been linked
      with malignancies, but the evidence is still weak in this respect. Nevertheless,
      oral microorganisms inevitably up-regulate cytokines and other inflammatory
      mediators that affect the complex metabolic pathways, and may thus be involved in
      carcinogenesis. Poor oral health associates statistically with prevalence of many
      types of cancer such as pancreatic and gastrointestinal cancer. This review
      presents possible carcinogenesis pathway involved in bacterial carcinogenesis,
      commonly implicated bacteria in oral carcinogenesis, and their role in cancer
      therapeutics as well. 

PMID- 24455520
TI  - Overview of recent developments in chronic lymphocytic leukemia.
AB  - Multiple advances have been made in our understanding of pathobiology of chronic
      lymphocytic leukemia (CLL). These developments in the laboratory include new
      prognostic markers, risk stratification of the disease and newer therapeutic
      agents in CLL. These advances in CLL have come a long way in the past three
      decades since the development of Rai and Binet clinical staging systems.
      Important strides in the pathobiology, from defining mutational status of IGHV,
      to B-cell receptor (BCR) signaling pathways and CLL microenvironment have made a
      major difference in our understanding of this disease. Mutational status of
      immunoglobulin heavy chain genes (IGHV), CD38 and Zap-70, chromosomal aberrations
      and newer mutations, are the most clinically relevant prognostic markers.
      Chemoimmunotherapy (CIT) has become the treatment of choice for young and fit CLL
      patients. Various inhibitors of BCR signaling pathways and immunomodulatory drugs
      have shown efficacy in clinical trials. The most recent advance is the use of
      chimeric antigen receptor therapy (CAR) based on autologous T-lymphocytes.
      Nevertheless, CLL remains an incurable disease today. Coordinated developments
      between laboratory and clinic will hopefully translate into a cure for CLL. This
      short review focuses on advances in prognostication and therapy in CLL. 

PMID- 24455521
TI  - Emergency percutaneous tracheostomy in two cancer patients with difficult airway:
      An alternative to cricothyroidotomy?
AB  - Inability to intubate and/or ventilate either due to distorted neck anatomy or
      restricted mouth opening is uncommon but potentially hazardous clinical scenario
      in head and neck cancer patients. Emergency cricothyroidotomy in such patients
      may provide a means of oxygenating the patient, but in practice has limitations
      and does not establish a definitive airway. We report 2 cases who had distorted
      face and neck anatomy in which percutaneous tracheostomy was done as an emergency
      life-saving procedure when other measures to obtain a definitive airway failed. 

PMID- 24455522
TI  - Osteoclastic giant cell rich metaplastic carcinoma in malignant phylloides: A
      rare entity.

PMID- 24455523
TI  - Gorham disease of mandible treated with post-operative radiotherapy.

PMID- 24455524
TI  - Composite pheochromocytoma.

PMID- 24455525
TI  - Mammographic screening for breast cancer: Are the chickens coming home to roost?

PMID- 24455526
TI  - Squamous cell carcinoma lung: Presented with bilateral lower limb deep venous
      thrombosis with gangrene formation.
AB  - Bilateral venous thrombosis due to underlying malignancy is a rare entity. It is
      worthy to search for malignancy in patients of bilateral venous gangrene. Our
      patient presented with severe bilateral leg pain as a result of venous gangrene.
      There was associated left sided massive pleural effusion with scalp nodule. Fine
      needle aspiration cytology of scalp nodule revealed metastatic squamous cell
      carcinoma and fiber optic bronchoscopy guided biopsy from growth at left upper
      lobe bronchus confirmed the case as squamous cell carcinoma lung. It was rare for
      squamous cell carcinoma lung to present as bilateral venous gangrene with
      anticardiolipin antibody negative. 

PMID- 24455527
TI  - Metastasis to left scapula with unknown primary: Approach to pathological
      diagnosis.
AB  - Bony metastasis is a frequent occurrence in malignancy. However, the clinical
      presentation and pathological findings may sometimes be more in favor of a
      primary bone lesion. In such cases, immunochemistry has a very important role to
      play in reaching a final diagnosis. We present the case of a 35 year male patient
      who was investigated for a lytic lesion in the left scapula and was finally
      diagnosed with metastatic adenocarcinoma with the help of immunostaining. 

PMID- 24455528
TI  - Tackling the crisis of antibiotic resistance.

PMID- 24455529
TI  - Xanthogranulomatous pyelonephritis: Rare presentation of a rare disease.
AB  - Xanthogranulomatous pyelonephritis is a rare chronic renal infection of unknown
      pathogenesis characterized by replacement of renal parenchyma by lipid filled
      macrophages frequently associated with an enlarged, non-functioning kidney and an
      obstructing calculus. We report a case of a 45 year old non diabetic female who
      presented with gradually enlarging renal mass with extensive retroperitoneal
      involvement and a non-functioning kidney with no evidence of obstructing stone or
      fat density and simulating malignancy. She was diagnosed as stage III
      Xanthogranulomatous pyelonephritis and managed with radical nephrectomy with
      favourable outcome. 

PMID- 24455530
TI  - Primary malignant melanoma of the vagina: A case report and review of literature.
AB  - A 60 year old woman presented in gynecology department with bleeding per vagina
      and subsequently histotpathologically, it was diagnosed as malignant melanoma of
      the vagina. She underwent excision biopsy. On metastatic work-up, Positron
      emission tomography (PET) scan proved that she had distant metastasis and
      received palliative radiotherapy and chemotherapy, with temozolamide. She is
      alive after one year. 

PMID- 24455531
TI  - Tissue is the real issue.

PMID- 24455532
TI  - Tamoxifen-induced endometrial carcinoma after a lag of 14 years.

PMID- 24455533
TI  - Anterior mediastinal masses: A study of 50 cases by fine needle aspiration
      cytology and core needle biopsy as a diagnostic procedure.
AB  - BACKGROUND: Mediastinal tumors are an uncommon abnormalities found in clinical
      practice. Anterior mediastinum is the common site and tissue diagnoses of
      anterior mediastinal masses (AMMs) are very important for correct therapeutic
      decision. OBJECTIVE: We evaluate the different malignant AMMs in various age
      groups and the sensitivity of fine needle aspiration cytology (FNAC) and core
      needle biopsy (CNB). Cytology smears are reviewed with particular emphasis on
      pitfalls in the cytological diagnosis. MATERIALS AND METHODS: This was a
      prospective study of 50 patients who were consulted for AMMs and underwent FNAC
      and CNB under guidance of ultrasound or computed tomography (CT) scan from 2006
      to 2011. Cytology smears and histological sections were evaluated in all
      patients. RESULTS: Among 50 cases, 36 were male and 14 were female. Most AMMs
      (52%) were identified in the fifth and sixth decades of life. Metastatic
      carcinoma and nonHodgkin's lymphoma are the common AMMs. Adequate tissue material
      was obtained in 49 of 50 cases by CNB. Of these 49 patients, 35 (71.42%) cases
      were diagnosed correctly by FNAC, whereas 14 (28.57%) cases were not diagnosed
      definitely by FNAC. The sensitivity of CNB for AMMs was 97.95%, significantly
      higher than FNAC (71.42%) (P < 0.05). CNB had statistically significant higher
      diagnostic rate than FNAC in the noncarcinoma group (100% versus 62.96%) (P <
      0.05). There is no significant difference of CNB and FNAC in carcinoma group (P >
      0.05). Diagnostic rate of FNAC was higher for carcinomatous lesions (81.81%) than
      for noncarcinomatous lesions (62.96%). CONCLUSION: Ultrasound or CT scan-guided
      CNB in combination with FNAC are safe, minimally invasive, and cost-effective
      procedure, which can provide a precise diagnosis in the AMMs, and may obviate the
      need for invasive surgical approach. FNAC usually suffice for carcinomatous
      lesions but CNB should be performed whenever the diagnosis of carcinoma is
      equivocal or noncarcinoma lesions are suspected.

PMID- 24455534
TI  - Cost-utility analysis of using nimotuzumab in end-stage cancerous patient: Is it
      too expensive?

PMID- 24455535
TI  - Huge chondromyxoid fibroma of proximal third tibia masquerading as an aneurysmal
      bone cyst: A rare case report.

PMID- 24455536
TI  - Computed tomogram guided fine-needle aspiration cytology of lung mass with
      histological correlation: A study in Eastern India.
AB  - BACKGROUND: Fine-needle aspiration cytology (FNAC) is an important and useful
      investigation, and is considered next to imaging in the rapid diagnosis of
      pulmonary mass lesion for the last few decades. AIMS: To assess the role of
      Computed Tomogram (CT) guided FNAC in pulmonary mass lesions; to analyze the
      results; and to compare with histopathological findings. MATERIALS AND METHODS:
      The clinical, radiological, and cytological data of 130 patients were
      prospectively studied who underwent CT guided FNAC from October 2009 through
      September 2011. Thereafter these patients underwent bronchoscopic/trucut
      biopsy/lobectomy, whatever clinically indicated. Smears and tissue sections were
      evaluated simultaneously to reach at a definite diagnosis. RESULTS: Out of 130
      cases, we found adequate FNAC smear and histopathology reports only in 124 cases.
      The age range varied from 35 to 73 years with the peak in the fifth to sixth
      decades. The benign lesions were 10 (8.07%) and malignant lesions were114
      (91.93%) shown by cytology. The most common tumor was adenocarcinoma (51.72%)
      followed by squamous cell carcinoma (22.41%) and small cell carcinoma 6.89%.
      Diagnostic accuracy of CT guided FNAC was 95%. Post procedural complications such
      as hemorrhage and chest pain were minimal and were noted only in three cases.
      CONCLUSION: CT guided FNAC of pulmonary masses provides simple, easy, and
      reliable method for reaching rapid tissue diagnosis with minimal complication.

PMID- 24455537
TI  - Adenoid cystic carcinoma of Bartholin's gland: Report of a case and review of
      literature.

PMID- 24455538
TI  - Lung cancer: Knowledge application gap.

PMID- 24455539
TI  - Clinical relevance of radiation pneumonitis in breast cancers.

PMID- 24455540
TI  - Abnormalities by pulmonary regions studied with computer tomography and clinical
      correlation following local-regional radiotherapy for breast cancer.
AB  - BACKGROUND: Adjuvant local-regional radiotherapy (RT) is commonly recommended for
      breast cancer patients. Postoperative adjuvant RT for breast cancer is associated
      with pulmonary side effects. This study was undertaken to measure the RT-induced
      pulmonary radiological changes with computer tomography (CT) scan using a CT
      adapted modification of the Arriagada classification system, and to correlate
      these changes to RT techniques, pulmonary complications, and pulmonary function.
      The aim of the study is to study pulmonary radiological abnormalities with CT
      following different RT techniques for breast cancer, and their correlation to
      pulmonary complications and reduction in forced vital capacity (FVC). MATERIALS
      AND METHODS: CT scans of the lungs were performed prior to and 4 months following
      RT in 53 breast cancer patients treated with local-regional RT. The radiological
      abnormalities were analyzed with a CT-adapted modification of a classification
      system originally proposed by Arriagada. The patients were monitored for RT
      induced pulmonary complications. FVC was measured prior to and 6 months following
      RT. Statistical analysis used were that increasing CT scores were correlated with
      pulmonary complications (P < 0.001). The correlation between density grade (0-3,
      4-9) and pulmonary complications (no complication vs slight/severe) was tested
      using Chi-square exact test for trend (2-sided). In addition, correlation between
      CT scores and FVC was done. RESULTS: Increasing CT scores were correlated with
      pulmonary complications (P < 0.001). The mean reduction of FVC for patients
      scoring 4-9 (-220 ml) was larger than for patients scoring 0-3 (-15 ml) (Spearson
      correlation coefficient significant at 0.01 level 2 tailed). But the mean
      reduction of FVC with greater volume of lung irradiated was not statistically
      different than lesser volume of lung irradiated (P > 0.05). CONCLUSIONS:
      Radiological abnormalities detected on CT images and scored with a modification
      of Arriagada's classification system can be used as an objective endpoint for
      pulmonary side effects in postmastectomy RT.

PMID- 24455541
TI  - Dose prediction accuracy of anisotropic analytical algorithm and pencil beam
      convolution algorithm beyond high density heterogeneity interface.
AB  - PURPOSE: It is well known that photon beam radiation therapy requires dose
      calculation algorithms. The objective of this study was to measure and assess the
      ability of pencil beam convolution (PBC) and anisotropic analytical algorithm
      (AAA) to predict doses beyond high density heterogeneity. MATERIALS AND METHODS:
      An inhomogeneous phantom of five layers was created in Eclipse planning system
      (version 8.6.15). Each layer of phantom was assigned in terms of water (first or
      top), air (second), water (third), bone (fourth), and water (fifth or bottom)
      medium. Depth doses in water (bottom medium) were calculated for 100 monitor
      units (MUs) with 6 Megavoltage (MV) photon beam for different field sizes using
      AAA and PBC with heterogeneity correction. Combinations of solid water, Poly
      Vinyl Chloride (PVC), and Styrofoam were then manufactured to mimic phantoms and
      doses for 100 MUs were acquired with cylindrical ionization chamber at selected
      depths beyond high density heterogeneity interface. The measured and calculated
      depth doses were then compared. RESULTS: AAA's values had better agreement with
      measurements at all measured depths. Dose overestimation by AAA (up to 5.3%) and
      by PBC (up to 6.7%) was found to be higher in proximity to the high-density
      heterogeneity interface, and the dose discrepancies were more pronounced for
      larger field sizes. The errors in dose estimation by AAA and PBC may be due to
      improper beam modeling of primary beam attenuation or lateral scatter
      contributions or combination of both in heterogeneous media that include low and
      high density materials. CONCLUSIONS: AAA is more accurate than PBC for dose
      calculations in treating deep-seated tumor beyond high-density heterogeneity
      interface.

PMID- 24455542
TI  - Different fractionation schedules of radiotherapy in locally advanced head and
      neck malignancy: A prospective randomized study to compare the results of
      treatment and toxicities of different protocols.
AB  - CONTEXT: Altered fractionated radiotherapy may have better result than
      conventional radiotherapy and concomitant chemoradiotherapy to treat locally
      advanced head and neck cancers. AIMS: Evaluation of the response and toxicities
      in different fractionated radiotherapy schedules in locally advanced head and
      neck cancer. MATERIALS AND METHODS: Sixty four histologically proved patients of
      locally advanced head and neck cancer were included in the study according to
      protocol and were randomized into three arms. Arm A (n = 21) received 66 Gy in 33
      fractions (5 fractions/week from Monday to Friday) single fraction daily in 61/2
      weeks along with concomitant chemotherapy (injection Cisplatin 30 mg/m(2)
      intravenous once weekly) for 6 weeks. Arm B (n = 21) received 66 Gy in 33
      fractions (6 fractions per week) single fraction daily in 51/2 weeks, and arm C
      (n = 22) received late hyperfractionation after 3 weeks; 30 Gy in 15 fractions in
      3 weeks followed by 1.4 Gy twice daily (time gap between 2 fractions were 6
      hours) for 15 days with a total of 72 Gy in 6 weeks. Response to treatment,
      compliance, and toxicities were compared in all the three arms. STATISTICAL
      ANALYSIS USED: Frequency table and chi square tests done. RESULTS: Baseline data
      were comparable in all the three arms. Complete response in arm A, arm B, and arm
      C were 15%, 26.315%, and 23.81%, respectively (P = 0.339). Grade 1 Neutropenia in
      arm A was 15%, arm B was 26.32%, and arm C was nil (P = 0.0486). CONCLUSION:
      Altered fractionation and concurrent chemoradiation showed similar response with
      comparable acute toxicities except nutropenia, which was significantly higher in
      arm B.

PMID- 24455543
TI  - Improving cancer care in Pakistan.

PMID- 24455544
TI  - Issues in current management of chronic myeloid leukemia: Importance of molecular
      monitoring on long term outcome.
AB  - Monitoring of CML patients while on therapy is vitally important and ENL has come
      up with specific guidelines for the same. Since we are currently talking about
      operational cure, this review shall focus on evaluating the emerging data to
      optimize response. This requires attention to all outstanding controversial
      issues. Only careful, accurate and regular monitoring with specific attention to
      grey areas will help us select first line therapy, decide when to discontinue
      TKIs and also move to second line TKIs in a timely manner. 

PMID- 24455545
TI  - Challenges in launching multinational oncology clinical trials in India.
AB  - In the recent past, there has been an impressive growth in the number of clinical
      trials launched worldwide, including India. Participation in well-designed
      oncology clinical trials is of advantage to Indian healthcare system in general,
      and cancer patients in particular. However, the number of clinical trials being
      run in India is not commensurate with the cancer burden prevailing in the
      country. In this article, the authors investigate the reasons for this
      discrepancy, highlight critical bottlenecks, and propose ways to ameliorate the
      situation. 

PMID- 24455546
TI  - A physician's personal experience with breast cancer: An interview.
AB  - Dr Moushumi Lodh is a physician who was diagnosed with breast cancer in the year
      2009. In this interview, she speaks to childhood friend and freelance medical
      writer, Dr Natasha Das about her life with cancer. When she was 22, Moushumi had
      a fibroadenoma removed from her breast. She had noticed a small new lump in her
      breast 16 years later and ignored it for over a year believing that it was one of
      those benign lumps again. She believes an early diagnosis could have paved way
      for better treatment options for her. In this interview, she urges women to be
      better aware, to do regular self-exams and to go for screening. If diagnosed with
      cancer, she says, one should not lose heart but should fight it with a positive
      spirit. Cancer, after all, is only another chronic disease that needs lifelong
      treatment and care. 

PMID- 24455547
TI  - The ethics of truth telling.

PMID- 24455548
TI  - Descending thoracic aorta dissection associated with esophageal carcinoma.
AB  - The association of aortic dissection with a malignancy is a rare finding and
      previous reports are usually those of primary aortic sarcomas. A 45-year-old male
      presented to us with chest pain and dysphagia for 1 month with a background
      history of obstructive airway disease and uncontrolled hypertension. In this
      report we present a case of typical descending aorta dissection with associated
      esophageal carcinoma. 

PMID- 24455549
TI  - Multiple trichoepitheliomas: A rare occurrence.
AB  - Trichoepitelioma is an extremely rare cosmetically disfiguring condition usually
      affecting the females. Trichoepitheliomas are benign lesions seen on the face,
      which are thought to derive from the hair follicle. Malignant transformation to
      basal cell carcinoma is rare and occurs late in the course of the disease These
      lesions are often misinterpreted and diagnosed clinically as neurofibromatosis or
      histpathologically as basal cell carcinoma. We report a case of multiple
      trichoepithelioma occurring in a male patient. The patient presented with
      multiple dermatologic growths on the face with varied histopathological
      presentations which have been described in detail. 

PMID- 24455550
TI  - Cancer control in South Asia: Awareness is key to success.

PMID- 24455551
TI  - Osteosarcoma relapse as pleural metastasis.
AB  - Osteosarcoma is the most common primary bone tumor in children and young adults
      arising from primitive mesenchymal bone-forming cells. The lung is the most
      common site of metastasis of osteosarcoma. Here, we report a case of a 14-year
      old male patient having osteosarcoma of tibia presenting to us for evaluation of
      left-sided pleural effusion after 4 years of mid-thigh amputation. Contrast
      enhanced computed tomography thorax revealed a large, heterogeneous, calcified
      mass (+277 H.U) at left upper and middle lobe along with massive left-sided
      pleural effusion. Thoracoscopy revealed a lung metastasis in the right upper and
      middle lobe along with 2-cm diameter mass found on the surface of parietal
      pleura. Lung tumor was resected and biopsy of the pleural mass was carried out.
      Histopathological examination from both the masses was suggestive of metastatic
      osteosarcoma. The case underlines the importance of performing thoracoscopy in
      patients of osteosarcoma who recur with lung metastasis. 

PMID- 24455552
TI  - Reply to: Metastasis to left scapula with unknown primary: Approach to
      pathological diagnosis.

PMID- 24455553
TI  - Does the cancer patient want to know? Results from a study in an Indian tertiary
      cancer center.
AB  - OBJECTIVE: The disclosure of the diagnosis of cancer is a distressing and complex
      issue. Families and doctors still do not tell patients when they have cancer in
      the belief that the patient does not want to know and telling him would lead to
      fear and depression. The aim of this survey was to evaluate the information needs
      of Indian cancer patients. MATERIALS AND METHODS: A cross-sectional survey of 300
      patients' views was conducted with the help of an adaptation of Cassileth's
      Information Needs questionnaire. RESULTS: A majority of cancer patients exhibited
      a strong need for information about illness and treatment. Ninety-four percent
      wanted to know if their illness was cancer. Most patients also wanted to know the
      chance of cure (92%). Age, education, and type of treatment significantly affect
      information preferences. Gender did not have an effect on information needs.
      CONCLUSION: This study showed that most of the patients wanted to know about
      their illness, treatment, side-effects, and chances of cure.

PMID- 24455554
TI  - Oncology knowledge gap among freshly passed interns in a Government Medical
      College of Eastern India.
AB  - OBJECTIVES: A survey was conducted among freshly passed undergraduate doctors of
      a medical college in Eastern India with the aim to investigate their exposure to
      oncology patients, their knowledge about various aspects of oncology patient
      management and their confidence in managing patients with cancer. MATERIALS AND
      METHODS: One hundred and twelve newly passed interns of a Government Medical
      College in Kolkata were interviewed using semi-structured partly open ended and
      partly closed end questionnaire. The questionnaire dealt with the qualitative and
      quantitative aspects of knowledge and perception of the interns about the problem
      of cancer and its management. RESULTS: A total of 82 interns responded to the
      questionnaire, with a response rate of 73.2%. About 53% of the respondents have
      seen less than five patients during their undergraduate ward/clinical postings.
      Among the respondents, 71% felt they were confident in diagnosing cancer, and
      about 56% were confident in counseling of patient and their relatives about
      cancer. About 63% were aware about the role of surgery; however, only 32% and
      37.5% were aware about the role of radiotherapy and chemotherapy, respectively. A
      dismal 12.5% were confident of care of terminal and late stage patients.
      Preparedness was correlated with exposure to patients with cancer (P = 0.03).
      Majority (87%) felt the need for incorporating oncology training at the
      undergraduate level and the most frequent method (67%) suggested for doing so was
      having separate posting in radiotherapy department/oncology wards. CONCLUSION:
      There is glaring knowledge gap among newly passed doctors and integrated oncology
      postings during undergraduate training and during internship may help seal this
      gap.

PMID- 24455555
TI  - Cancer related knowledge and behavior among women across various socio-economic
      strata: A study from Delhi, India.
AB  - BACKGROUND: Cancer is predicted to be an increasingly important cause of
      morbidity and mortality in the next few decades worldwide. One important step in
      reducing the burden of morbidity and mortality from cancers is awareness among
      the population about the causes and prevention of cancers. OBJECTIVE: To study
      the knowledge and preventive behavior regarding common cancers among the women
      from an area of Delhi, India. STUDY DESIGN: Cross-sectional study. SETTING: Four
      purposively selected residential areas representing various socio-economic
      strata, in North-East Delhi. PARTICIPANTS: One thousand two hundred and six women
      in the age group 18-60 years. STATISTICAL ANALYSIS: Proportions, Chi-square test.
      RESULTS: Majority of the women (43.9%) were graduates while 10.4% were
      illiterate. The awareness about breast cancer was maximum with 73.8% of the
      respondents being aware about it. The proportions of women aware about the other
      cancers were low. Only 52 (4.3%) had ever been for a preventive check-up for
      cancer. The most common cancer checkup for which the respondents reported
      visiting a hospital was, breast cancer. Among the respondents, 46 (3.8%) reported
      having a female member in their family who ever had cancer. Five hundred and
      seventy seven (47.8%) had not seen any message regarding cancers common in
      females in any mass media. Women with a higher education level, having a female
      family member with cancer, and those who could recall mass media message
      regarding cancers, were significantly more likely to have had a preventive cancer
      checkup for self. CONCLUSION: The knowledge and actual preventive behavior about
      cancers was found to be low among the women. Increased mass media exposure and
      targeted strategies can possibly increase the awareness and the cancer-related
      health behavior among the women.

PMID- 24455556
TI  - Adjuvant colon cancer chemotherapy: Is there an Indian standard of care?

PMID- 24455557
TI  - The real picture of cancer care in the developing countries.

PMID- 24455558
TI  - Comparative efficacy of 5flourouracil/calcium leucovorine versus
      5flourouracil/calcium leucovorine plus oxaliplatin in the adjuvant treatment of
      colonic carcinoma in Kashmir.
AB  - AIM: This prospective, randomized comparative study conducted in Kashmir
      evaluated the clinical profile of colonic carcinoma and the efficacy, side
      effects and survival advantage of adjuvant treatment with 5FU/CLV versus FOLFOX7.
      MATERIALS AND METHODS: Between 2007 and 2009, the clinical profiles of 50
      patients enrolled and randomized equally into Arm A receiving 5FU/CLV alone (Mayo
      Clinic Regimen) and Arm B receiving the FOLFOX7 regimen (including oxaliplatin)
      were evaluated. RESULTS: Majority of the patients were in the 5(th) and 6(th)
      decade of life (males 70% versus females 30%), and most were from urban
      dwellings. Consumption of red meat, obesity and physical inactivity were common
      risk factors. A family history of colonic carcinoma was reported in 12% of the
      patients. Event-free and disease-free survival for the two arms were: Arm A -
      12.8 +/- 5 months and 14.2 +/- 6 months; Arm B - 13.0 +/- 6.7 months and 13.1 +/-
      6 months, respectively. Treatment-related morbidity was significant in Arm B
      whereas general well being and surrogate laboratory markers including a hemogram,
      favored Arm A. CONCLUSION: The clinical profile, risk factors and familial
      predisposition of Kashmiri colonic carcinoma patients matches that of colon
      cancer patients elsewhere. There was no added survival advantage by adding
      oxaliplatin to 5FU and CLV. Although the interim results showed that the Mayo
      Clinic Regimen has a better total survival advantage compared with the FOLFOX7
      regimen, the results were not statistically significant. The Mayo Clinic Regimen
      was better than the FOLFOX7 regimen in terms of the toxicity profile. However,
      this finding needs to be studied further. The main idea of conducting this study
      was to reveal that there is no added advantage of adding oxaliplatin to 5FU and
      CLV, thereby (a) reducing the toxicity (b) and lowering cost of therapy.

PMID- 24455559
TI  - Primary mediastinal choriocarcinoma.

PMID- 24455560
TI  - Is the heart truly noble?

PMID- 24455561
TI  - Dizziness, lacunar infarction, thrombocytopenia in a cancerous patient.

PMID- 24455562
TI  - A new systems approach to combat arsenic induced carcinogenesis.

PMID- 24455563
TI  - Cardiac myxoma: A surgical experience of 38 patients over 9 years, at SSKM
      hospital Kolkata, India.
AB  - BACKGROUND: Cardiac myxoma is the most common benign intracardiac tumor. We
      studied its clinical presentation, morbidity, mortality and recurrence following
      surgery over a period of 9 years. MATERIALS AND METHODS: This study was performed
      at cardiothoracic and vascular surgery department of a tertiary level hospital of
      eastern India, Seth Sukhlal Karnani Memorial hospital, Institute of Post Graduate
      Medical Education and Research Kolkata. Near 6000 cardiac cases were operated at
      our center over this period. Preoperative diagnosis was made with clinical
      presentation and preoperative echocardiography. Complete tumor excision was done
      and all patients were followed up for recurrence and complications. RESULT: A
      total of 38 cases of cardiac myxoma were operated over a period from October 2002
      to October 2011. Cardiac myxoma constituted about 0.6% of all cardiac cases
      operated at our institute. This most commonly presented at fifth decade of life.
      Of these, 35 cases were left atrial and 2 cases were right atrial, and 1 case was
      having both atrial involvements. The left atrial myxoma mostly presented as
      mitral stenosis and very few presented with embolic and constitutional symptoms.
      No death or recurrence was observed during the follow up period. CONCLUSION:
      Cardiac myxomas form a very small percentage of the cardiac cases. A high index
      of suspicion is essential for diagnosis. Echocardiography is the ideal diagnostic
      tool as also for follow-up. Immediate surgical treatment is indicated in all
      patients. Cardiac myxomas can be excised with a low rate of mortality and
      morbidity.

PMID- 24455564
TI  - Lung cancer presenting as visual impairment.

PMID- 24455565
TI  - Lung cancer and Hepatitis C virus.

PMID- 24455566
TI  - Vascular endothelial growth factor expression in ovarian serous carcinomas and
      its effect on tumor proliferation.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF), an endothelial mitogen,
      acts through VEGF receptors (VEGFRs) on the endothelial cells. During neoplastic
      transformation, it is hypothesized that the tumor expresses VEGF and also acquire
      VEGF receptor, enabling VEGF action in an autocrine and paracrine manner with
      varied effects on the tumor growth and progression. This study on ovarian serous
      carcinomas (OSCs) was done to determine the expression of VEGF and to correlate
      it with tumor proliferation. MATERIAL AND METHODS: Forty cases of OSCs were
      included. Immunohistochemistry was performed for VEGF and Ki-67. The VEGF slides
      were assigned an immunohistochemical score based on the staining intensity (a)
      and the percentage of tumor cells staining (b). The sum of both (a) and (b)
      ranged from 0-6. VEGF was considered positive when the score was more than 2. For
      Ki-67, maximally immunostained areas were selected; 500 cells counted and
      positive fraction determined. Mann Whitney test was used to determine the
      difference in the median value of Ki-67 between VEGF positive tumors and VEGF
      negative tumors. RESULTS: Of the 40 cases, 32 cases had a VEGF score of >2
      (positive) and 8 cases had VEGF score <2 (negative). The Ki-67 score ranged from
      2-98%, with mean of 51%. The median Ki-67 index was much higher in VEGF positive
      cases as compared to VEGF negative tumors (57.5% vs. 40%). However, the
      difference in the two categories did not reach statistical significance (P =
      0.45, Mann Whitney test). CONCLUSION: Ovarian serous carcinomas express VEGF in a
      significant number of cases (80% in the present study) although its potential
      mitogenic effect on tumor cells was not confirmed.

PMID- 24455568
TI  - Systemic metastasis in a carotid body tumor: A rare presentation of a rare tumor.

PMID- 24455567
TI  - Crizotinib: A comprehensive review.
AB  - Anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small
      subset of non-small-cell lung cancers. ALK-positivity confers sensitivity to
      small-molecule ALK kinase inhibitors, such as crizotinib. The integration of
      crizotinib into standard treatment practice in NSCLC will rest on the widespread
      implementation of an effective screening system for newly diagnosed patients with
      NSCLC which is flexible enough to incorporate new targets as treatments are
      developed for them. Phase I and II studies of crizotinib in ALK-positive lung
      cancer have demonstrated significant activity and impressive clinical benefit,
      which led to its early approval by USFDA in 2011. Although crizotinib induces
      remissions and extends the lives of patients, there have been reports of emerging
      resistance to Crizotinib therapy. In this review, we discuss the history,
      mechanism of action, uses, adverse effects, dose modifications and future
      challenges and opportunities for patients with ALK-positive lung cancers. 

PMID- 24455569
TI  - A systematic approach to diagnosis of cystic brain lesions.
AB  - Brain metastasis is the most common intracranial tumor in adults. The incidence
      of brain metastasis is rising with the increase in survival of cancer patients.
      Magnetic resonance imaging with contrast enhancement is the imaging procedure of
      choice to diagnose and characterize brain metastases. Multiple lesions with
      marked vasogenic edema and mass effect are typically seen in patients with brain
      metastases. The classical appearance of a metastasis is a solid enhancing mass
      with well-defined margins and extensive edema. Occasionally, central necrosis
      produces a ring enhancing mass. Here, we report a case of Non Small Cell Lung
      Cancer with multiple ring enhancing lesions in brain, and the approach to
      diagnosis of such patients. 

PMID- 24455570
TI  - Cancer care scenario in Bangladesh.
AB  - Bangladesh is a developing country that is facing many challenges, especially in
      the health sector. Cancer management is a priority due to the current trend of
      increased incidence in this region. In this article, the current scenario of
      cancer in Bangladesh and its management with brief history is outlined. The
      combined effort of government and private sector is highlighted with the gradual
      progress in cancer management. Recent introduction of the state-of-the-art
      facilities and the training facilities for human resource development are also
      outlined. The existing challenges and cooperation from local NGOs and other
      overseas sources are also highlighted to provide an insight regarding possible
      ways to tackle these challenges to ensure a better future. 

PMID- 24455571
TI  - Brief report on pediatric oncology in Bangladesh.
AB  - Cancer in children is emerging as a significant threat to life as deaths from
      infections and malnutrition have begun to decrease due to concerted maternal and
      child health initiatives. Efforts are being made to create a comprehensive
      service for children with Cancer. The major challenges to be overcome are
      professional and public awareness, late diagnosis, perceptions of incurablity,
      treatment refusal and abandonment, toxic deaths and drug costs/inconsistent
      availability. 

PMID- 24455572
TI  - Relentless effort towards improving childhood cancer care: Need of the hour.

PMID- 24455573
TI  - Adjuvant chemotherapy in carcinoma colon: Is there a rationale to change practice
      for Asian patients?

PMID- 24455574
TI  - Link between p53 isoforms and angiogenesis: Current prospects.

PMID- 24455575
TI  - Setting up low-risk bone marrow transplantation for children with thalassemia may
      facilitate pediatric cancer care.
AB  - BACKGROUND: In many South Asian countries there is shortage of centers providing
      care for pediatric malignancies. This report describes the experience of the
      Cure2Children Foundation (C2C) in supporting, both financially and
      professionally, the startup of two bone marrow transplant (BMT) centers, one in
      Pakistan and one in India, for the cure of transfusion-dependent thalassemia.
      Even though transplantation is generally considered as a more complex and
      advanced step relatively to basic pediatric cancer care, the authors argue that
      BMT for low-risk thalassemia patients with a matched sibling is a relatively
      simple procedure amenable to focused training. MATERIALS AND METHODS: Since 2008
      the C2C, an Italian Nongovernmental Organization (NGO), has supported a BMT
      network in Pakistan. The primary aim of this project was to assess feasibility,
      outcomes, and costs of matched-related BMT for thalassemia in young low-risk
      children employing a well established and quite tolerable strategy employed in
      Italy. This initiative relied primarily on focused training and task-shift
      strategies within a structured cooperation program. The initial success of that
      strategy led to its replication in India with 100 total BMTs performed over the
      past 4 years, 91 of which were for thalassemia major. RESULTS: Low-risk matched
      related BMT in children younger than 5 years could deliver a 92% thalassemia-free
      survival with 100% performance score and no extensive chronic graft versus host
      disease (GVHD), for an average cost of 10,000 USD per BMT. Within an existing
      hospital facility, 50,000 USD were sufficient to renovate and fully equip a 2-3
      bedded start up BMT unit capable of performing safe low-risk compatible marrow
      transplantation. CONCLUSIONS: In low resource settings matched-related low-risk
      BMT for thalassemia can be performed with outcomes comparable to richer countries
      and with a fraction of the costs. Within structured and intensive cooperation,
      good outcomes can be obtained from the very beginning. This observation may have
      important implications to increase access to cure for both nonmalignant and
      malignant.

PMID- 24455576
TI  - Understanding the perceptions of children battling cancer about self and others
      through drawing.
AB  - BACKGROUND: Childhood cancer is a stressful experience and may cause a change in
      the child's perception of himself/ herself, the family and the world around him/
      her. AIMS: This study sought to (a) explore the self-perception of children; and
      (b) examine the relation of children with others. MATERIALS AND METHODS: The
      total population of the study consisted of all the children, undergoing cancer
      treatment at Children Cancer Hospital, located in Karachi. The participants were
      asked to draw a drawing on self and others. Through qualitative approach
      (phenomenology), themes and sub-themes were derived. RESULTS: Using purposive
      sampling, the total sample size drawn for this study was 78 children aged 7-12,
      receiving treatment for cancer (1st stage) at the Children Cancer Hospital,
      Karachi, Pakistan. The drawings of the children were categorized into facial
      expressions, self images and family ties. Within each category, there were sub
      categories. Under facial expressions, the common emotions reflected were sadness,
      seriousness, anger; and pain. The self-image pictures uniformly reflected low
      self-esteem, especially focusing on hair loss, missing body parts. Under the
      category of family ties, most of the children's drawings reflected their
      isolation or emotional detachment from or abandonment by their family members.
      CONCLUSIONS: The study concludes that the self- image of most of the participants
      is deteriorated and they are socially isolated. Social and moral support can
      bring positive emotional development and helps to correct their self-perception.

PMID- 24455577
TI  - "Stump" of broad ligament: A rare entity with review of literature.

PMID- 24455578
TI  - Bigger is not better! The risk of obesity and risk of breast cancer incidence and
      recurrence in the Indian subcontinent.

PMID- 24455579
TI  - Brain metastasis from neuroendocrine tumor of the gallbladder: a rare entity.

PMID- 24455580
TI  - Rare case: Monophasic pleuropulmonary synovial sarcoma.

PMID- 24455581
TI  - Association between body mass index and risk of breast cancer among females of
      north India.
AB  - BACKGROUND: Worldwide, breast cancer is most common cancer among women. In India
      and other developing countries, breast carcinoma ranks second only to cervical
      carcinoma among women. Although studies have been done globally, to find
      association between BMI and breast cancer, very few studies in India document any
      such association. PURPOSE: To find out the association between BMI and breast
      cancer. MATERIALS AND METHODS: A Case-control study was done from August 2009 -
      July 2010 in the wards of General Surgery and Oncosurgery at Pt.B.D.Sharma, PGIMS
      Rohtak, Haryana. A total of 128 histopathologically confirmed new cases of breast
      cancer during the study period were taken as cases. Equal number of controls was
      selected by simple random sampling. Controls were matched for age with range of
      +/-2 years. Subjects were interviewed using a pretested questionnaire after
      obtaining written informed consent. Data were analyzed by applying appropriate
      statistical tests using SPSS version 17. RESULTS: Age group of the cases was 25 -
      78 years, while that of the controls was 24 - 79 years. Proportion of cases and
      controls living in rural areas were more than those living in urban areas. A
      significant association of breast cancer cases was found with high BMI and high
      fat intake. CONCLUSION: Obesity and high fat intake are the significant risk
      factors, which are modifiable. So women should be encouraged to take care of all
      these factors. Maximum cases presented in late stages so public awareness of this
      fatal disease must be developed.

PMID- 24455582
TI  - Prostate specific antigen change after administration of nimotuzumab in prostate
      cancer.

PMID- 24455583
TI  - Conventional external beam volumes for cervical cancer: Are they adequate?

PMID- 24455584
TI  - Dosimetric comparison between conventional and conformal radiotherapy for
      carcinoma cervix: Are we treating the right volumes?
AB  - BACKGROUND AND PURPOSE: Conventional portals, based on bony anatomy, for external
      beam radiotherapy for cervical cancer have been repeatedly demonstrated as
      inadequate. Conversely, with image-based conformal radiotherapy, better target
      coverage may be offset by the greater toxicities and poorer compliance associated
      with treating larger volumes. This study was meant to dosimetrically compare
      conformal and conventional radiotherapy. MATERIALS AND METHODS: Five patients of
      carcinoma cervix underwent planning CT scan with IV contrast and targets, and
      organs at risk (OAR) were contoured. Two sets of plans-conventional and conformal
      were generated for each patient. Field sizes were recorded, and dose volume
      histograms of both sets of plans were generated and compared on the basis of
      target coverage and OAR sparing. RESULTS: Target coverage was significantly
      improved with conformal plans though field sizes required were significantly
      larger. On the other hand, dose homogeneity was not significantly improved. Doses
      to the OARs (rectum, urinary bladder, and small bowel) were not significantly
      different across the 2 arms. CONCLUSION: Three-dimensional conformal radiotherapy
      gives significantly better target coverage, which may translate into better local
      control and survival. On the other hand, it also requires significantly larger
      field sizes though doses to the OARs are not significantly increased.

PMID- 24455585
TI  - Imaging in Lhermitte: Duclos disease.

PMID- 24455586
TI  - Parasagittal hemangiopericytoma with late presentation of liver metastases: Case
      report and review of literature.

PMID- 24455587
TI  - Conventional four field radiotherapy versus computed tomography-based treatment
      planning in cancer cervix: A dosimetric study.
AB  - BACKGROUND: With advancements in imaging, wide variations in pelvic anatomy have
      been observed, thus raising doubts about adequate target volume coverage by
      conventional external radiotherapy fields based on bony landmarks. The present
      study evaluates the need for integrating computed tomography (CT)-based planning
      in the treatment of carcinoma cervix. AIMS: To estimate inadequacies in target
      volume coverage when using conventional planning based on bony landmarks.
      MATERIALS AND METHODS: The study consisted of 50 patients. Target volume
      delineation was done on planning CT scans, according to the guidelines given in
      literature. The volume of target receiving 95% of prescribed dose (V95) was
      calculated after superimposing a conventional four field box on digitally
      reconstructed radiograph. The geographic miss with conventional four field box
      technique was compared with the CT-based target volume delineation. RESULTS: In
      48 out of 50 patients, the conventional four field box failed to encompass the
      target volume. The areas of miss were at the superior and lateral borders of the
      anterior-posterior fields, and the anterior border of the lateral fields. The
      median V95 for conventional fields marked with bony landmarks was only 89.4% as
      compared to 93% for target delineation based on CT contouring. CONCLUSIONS: Our
      study shows inadequate target volume coverage with conventional four field box
      technique. We recommend routine use of CT-based planning for treatment with
      radiotherapy in carcinoma cervix.

PMID- 24455588
TI  - Vascular endothelial growth factor as an angiogenic swich in ovarian carcinoma.

PMID- 24455589
TI  - Osteosarcoma metastases in penis.

PMID- 24455590
TI  - The role of surgery in locally advanced carcinoma of cervix after sub-optimal
      chemoradiation: Indian scenario.
AB  - BACKGROUND: Standard treatment of advanced cervical cancer is concurrent
      chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic
      external beam radiotherapy (EBRT) with the concomitant platinum based
      chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central
      disease. Management of patients who are suboptimally treated, especially, after
      unsuccessful ICBT insertion is not well-defined. This study explores the role of
      hysterectomy in these patients. MATERIALS AND METHODS: From January 2006 to
      December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT
      insertion was unsuccessful, were analyzed retrospectively. Operable patients with
      no parametrial involvement underwent hysterectomy and outcomes (recurrence free
      and overall survival) were noted. RESULTS: The major complications in post
      operative period were wound infection, paralytic ileus and bladder atony all of
      which were conservatively managed with no mortality. At median follow-up of 36
      months (range 12-60 months) there was no recurrence in patients with stage 1B2
      and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was
      71%. CONCLUSION: Many patients in Indian scenario receive suboptimal therapy in
      locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra
      fascial hysterectomy can be a good alternative for these patients.

PMID- 24455591
TI  - Betel leaf: Revisiting the benefits of an ancient Indian herb.

PMID- 24455592
TI  - Malignant peripheral nerve sheath tumor in spine: Two case reports.

PMID- 24455593
TI  - Giant adrenal hemorrhagic cyst: An unusual abdominal lump.

PMID- 24455594
TI  - Salivary ascorbic acid levels in betel quid chewers: A biochemical study.
AB  - BACKGROUND: Quid chewing practice has been a part of our tradition since
      centuries with little known evidence of oral cancer. However, recent trends show
      a rise in occurrence of oral cancer often associated with tobacco and arecanut
      usage. Ascorbic acid is an important salivary antioxidant. Betel leaf which is
      used in quid is known to contain ascorbic acid. AIM: The aim of our study was to
      assess the salivary levels of ascorbic acid in traditional quid chewers so as to
      determine whether the betel leaf has protective antioxidant action. MATERIALS AND
      METHODS: Salivary ascorbic acid levels of 60 subjects were estimated using the
      Dinitrophenyl hydrazine method. RESULTS: The results revealed that quid chewers
      who used betel leaf had higher salivary ascorbic acid content compared to
      nonbetel leaf quid chewers. This could possibly be due to the protective
      antioxidants in the betel leaf.

PMID- 24455595
TI  - Pediatric solitary osteochondroma of T1 vertebra causing spinal cord compression:
      A case report.

PMID- 24455596
TI  - Traumatic ulcerative eosinophillic granuloma with stromal eosinophilia of tongue.

PMID- 24455598
TI  - Metastatic oral soft-tissue lesions: An incidental finding in four cases.

PMID- 24455597
TI  - Oral submucous fibrosis and plasma lipid profile.

PMID- 24455599
TI  - Alteration in plasma lipid profile in oral submucous fibrosis patients: A case
      control study.
AB  - BACKGROUND: Lipids are major cell membrane components essential for various
      biological functions including cell growth and division of normal and malignant
      tissue. They are also required for maintenance of structural and functional
      integrity of all biological membranes. Alteration in the plasma lipid profile has
      been associated with a variety of cancers and precancerous conditions including
      those of the head and neck region. AIM: The present study aimed to evaluate the
      alteration in plasma lipid profile in oral submucous fibrosis (OSF) patients.
      MATERIALS AND METHODS: A total of 30 patients were included in the study, 20 with
      oral submucous fibrosis and 10 healthy controls. Fasting plasma lipid profile
      including Total Cholesterol (TC), Very Low Density Lipoproteins (VLDL), Low
      Density Lipoproteins (LDL), High Density Lipoproteins (HDL) and Tri-Glycerides
      (TG) were measured using semiautomatic analyser. The data obtained were analysed
      using independent sample 't' test. RESULTS: A statistically significant decrease
      in plasma total cholesterol, LDL and HDL was observed in patients with OSMF as
      compared to the controls, but it was not statistically significant for VLDL and
      TG values. CONCLUSION: The results of the present study show that there is an
      inverse relationship between lipid profile and the presence of oral submucous
      fibrosis. Hence, alteration in plasma lipid profile may have a diagnostic role in
      the future and can be used as a biochemical indicator to detect the initial
      changes seen in the neoplastic process.

PMID- 24455600
TI  - Juvenile granulosa cell tumor with an unusual immunoprofile, presenting as
      precocious puberty.

PMID- 24455601
TI  - Intussusception through an ileostomy.

PMID- 24455602
TI  - Cystic lesions of the pancreas: Improved understanding, diagnostics and refined
      outcomes.

PMID- 24455603
TI  - A case of synchronous double malignancy: Invasive bladder cancer and
      Leiomyosarcoma of extremity and review of literature.

PMID- 24455604
TI  - An unusual case of clear cell sarcoma presenting as multiple abdominal masses
      confirmed by RT-PCR.

PMID- 24455606
TI  - Revision of Prasad's social classification and provision of an online tool for
      real-time updating.

PMID- 24455605
TI  - Solid and cystic papillary neoplasm of pancreas: A clinic-pathological and
      immunohistochemical study: A tertiary care center experience.
AB  - BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPT) is a rare tumor of
      low malignant potential, mostly described in young women. MATERIALS AND METHODS:
      In this retrospective study from January 2000 - December 2010, there were 50
      pancreatic tumors. In this period, four SPTs were encountered, which were
      analyzed with respect to clinical, imaging, histopathological, and
      immunohistochemical findings. RESULTS: There was a female preponderance with mean
      age of 22.2 years. Two of the tumors were located in head of the pancreas and two
      in the body and tail region. On imaging, majority were large cystic tumors.
      Histopathologically, they exhibited extensive necrosis and presence of pseudo
      papillae in viable areas. Immunohistochemically, they were positive for alpha-1
      anti-trypsin, alpha-1-anti-chymotrypsin, vimentin, CD10, and CD99. Progesterone
      receptor and p53 exhibited mild positivity in all of the four cases, whereas
      neuron specific enolase (NSE), synaptophysin, and chromogranin showed focal
      positivity in one case. CONCLUSION: Despite its non-specific clinical, imaging,
      and even immunohistochemical features, characteristic gross and microscopic
      findings provide reliable diagnosis of SPTs.

PMID- 24455607
TI  - Whipple resection: The need for specialization, standardization and
      centralization.

PMID- 24455608
TI  - Pleural effusion in a cancerous patient with acute cerebrovascular accident: A
      case study.

PMID- 24455609
TI  - Impact of reconstruction methods and pathological factors on survival after
      pancreaticoduodenectomy.
AB  - BACKGROUND: Surgery remains the mainstay of therapy for pancreatic head (PH) and
      periampullary carcinoma (PC) and provides the only chance of cure. Improvements
      of surgical technique, increased surgical experience and advances in anesthesia,
      intensive care and parenteral nutrition have substantially decreased surgical
      complications and increased survival. We evaluate the effects of reconstruction
      type, complications and pathological factors on survival and quality of life.
      MATERIALS AND METHODS: This is a prospective study to evaluate the impact of
      various reconstruction methods of the pancreatic remnant after
      pancreaticoduodenectomy and the pathological characteristics of PC patients over
      3.5 years. Patient characteristics and descriptive analysis in the three variable
      methods either with or without stent were compared with Chi-square test.
      Multivariate analysis was performed with the logistic regression analysis test
      and multinomial logistic regression analysis test. Survival rate was analyzed by
      use Kaplan-Meier test. RESULTS: Forty-one consecutive patients with PC were
      enrolled. There were 23 men (56.1%) and 18 women (43.9%), with a median age of 56
      years (16 to 70 years). There were 24 cases of PH cancer, eight cases of PC, four
      cases of distal CBD cancer and five cases of duodenal carcinoma. Nine patients
      underwent duct-to-mucosa pancreatico jejunostomy (PJ), 17 patients underwent
      telescoping pancreatico jejunostomy (PJ) and 15 patients pancreaticogastrostomy
      (PG). The pancreatic duct was stented in 30 patients while in 11 patients, the
      duct was not stented. The PJ duct-to-mucosa caused significantly less leakage,
      but longer operative and reconstructive times. Telescoping PJ was associated with
      the shortest hospital stay. There were 5 postoperative mortalities, while
      postoperative morbidities included pancreatic fistula-6 patients, delayed gastric
      emptying in-11, GI fistula-3, wound infection-12, burst abdomen-6 and pulmonary
      infection-2. Factors that predisposed to development of pancreatic leakage
      included male gender, preoperative albumin < 30g/dl, pre-operative hemoglobin <
      10g/dl and non PJ-duct to mucosa type of reconstruction. The ampullary cancers
      presented at an earlier stage and had a better prognosis than pancreatic cancer
      and cholangiocarcinoma. Early stage (I and II), negative surgical margin, well
      and moderate differentiation and absence of lymph node involvement significantly
      predicted for longer survival. CONCLUSIONS: PJ duct-to-mucosa anastomosis was
      safe, caused least pancreatic leakage and least blood loss compared with the
      other methods of reconstruction and was associated with early return back to home
      and prolonged disease free and overall survival.

PMID- 24455610
TI  - Multiple myeloma presenting with focal segmental glomerulosclerosis.

PMID- 24455611
TI  - The cure for a racing heart.

PMID- 24455613
TI  - Paraspinal mass as a presentation in relapsed Hodgkin lymphoma.

PMID- 24455612
TI  - Positron emission tomography-computed tomography in the management of lung
      cancer: An update.
AB  - This communication presents an update on the current role of positron emission
      tomography-computed tomography (PET-CT) in the various clinical decision-making
      steps in lung carcinoma. The modality has been reported to be useful in
      characterizing solitary pulmonary nodules, improving lung cancer staging,
      especially for the detection of nodal and metastatic site involvement, guiding
      therapy, monitoring treatment response, and predicting outcome in non-small cell
      lung carcinoma (NSCLC). Its role has been more extensively evaluated in NSCLC
      than small cell lung carcinoma (SCLC). Limitations in FDG PET-CT are encountered
      in cases of tumor histotypes characterized by low glucose uptake (mucinous forms,
      bronchioalveolar carcinoma, neuroendocrine tumors), in the assessment of brain
      metastases (high physiologic 18F-FDG uptake in the brain) and in cases presenting
      with associated inflammation. The future potentials of newer PET tracers beyond
      FDG are enumerated. An evolving area is PET-guided assessment of targeted therapy
      (e.g., EGFR and EGFR tyrosine kinase overexpression) in tumors which have
      significant potential for drug development. 

PMID- 24455614
TI  - Primary extragonadal pure yolk sac tumor in a post-menopausal female.

PMID- 24455616
TI  - Extrauterine mixed endometrial stromal-smooth muscle tumor: Report of an unusual
      entity.

PMID- 24455617
TI  - Malignant fibrous histiocytoma of the chest wall: A rare differential.

PMID- 24455615
TI  - Metastatic colorectal cancer-prolonging overall survival with targeted therapies.
AB  - This review provides an updated overview of the management of metastatic
      colorectal cancer (CRC). With widespread application of personalized therapy
      based on specific patient and tumor characteristics, this will enable the
      oncologists to optimize overall survival while maintaining quality of life. The
      role of k-ras and braf testing in helping select systemic therapy that includes
      cetuximab or bevacizumab is clarified. Current management of metastatic CRC is
      based on careful attention to these finer points, explained in this article. 

PMID- 24455618
TI  - Efficacy and safety of human papillomavirus vaccine for primary prevention of
      cervical cancer: A review of evidence from phase III trials and national
      programs.
AB  - The Human Papillomavirus (HPV) vaccines have been widely introduced in the
      national immunization programs in most of the medium and high income countries
      following endorsement from national and international advisory bodies. HPV
      vaccine is unique and its introduction is challenging in many ways - it is the
      first vaccine developed to prevent any cancer, the vaccine is gender specific, it
      targets adolescent females who are difficult to reach by any health intervention
      programs. It is not unusual for such a vaccine to face scepticism and
      reservations not only from lay public but also from professionals in spite of the
      clinical trial results convincingly and consistently proving their efficacy and
      safety. Over the last few years millions of doses of the HPV vaccine have been
      administered round the world and the efficacy and safety data have started coming
      from the real life programs. A comprehensive cervical cancer control program
      involving HPV vaccination of the adolescent girls and screening of the adult
      women has been proved to be the most cost-effective approach to reduce the burden
      of cervical cancer. The present article discusses the justification of HPV
      vaccination in the backdrop of natural history of cervical cancer, the mechanism
      of action of the vaccines, efficacy and safety data from phase III randomized
      controlled trials as well as from the national immunization programs of various
      countries. 

PMID- 24455619
TI  - Bone marrow transplantation for thalassemia: How much is a child's life worth?

PMID- 24455620
TI  - Tell the truth, but be gentle.

PMID- 24455621
TI  - Fluoride carcinogenesis: The jury is still out!

PMID- 24455622
TI  - Is human papillomavirus vaccination likely to be a useful strategy in India?
AB  - Two vaccines that protect against infection by some of the oncogenic human
      papillomavirus (HPV) subtypes have recently been licensed for use in population
      based vaccination strategies in many countries. However, these products are being
      promoted as 'cervical cancer vaccines' based on inadequate data. Specifically,
      there remain several concerns about the duration of immunogenicity, length of
      follow-up of trial subjects, endpoints chosen in vaccine trials, applicability of
      trial results to real populations, the safety of these products, and their cost
      effectiveness as public health interventions. Furthermore, it is unlikely that
      vaccination will obviate the need for setting up robust and cost-effective
      screening programs in countries like India. This article will discuss various
      aspects of HPV vaccination from a public health perspective, especially from the
      point of view of its relevance to India and other South Asian countries. 

PMID- 24455623
TI  - The fractionation conundrum: Are we still missing a piece of the puzzle?

PMID- 24455624
TI  - Accuracy of dose calculation algorithms in Eclipse treatment planning system: An
      update.

PMID- 24455625
TI  - Does HPV vaccination prevent cervical cancer?

PMID- 24455626
TI  - Primary squamous cell carcinoma of stomach: A rare case report.

PMID- 24455627
TI  - Significance of early detection of oral malignant melanoma in improving
      prognosis.

PMID- 24455628
TI  - Geriatric oncology: The need of the hour.

PMID- 24455629
TI  - A strategy to increase the uptake of cervical cancer screening in India: A lesson
      from the ongoing programs.

PMID- 24455630
TI  - Assessment of cancer care in Indian elderly cancer patients: A single center
      study.
AB  - BACKGROUND AND PURPOSE: This prospective study aimed to assess the profiles of
      elderly cancer patient to optimize cancer care in Indian setup. The profiles have
      been compared with that of younger patients in terms of epidemiological, clinical
      data, co-morbidity, treatment, toxicity, clinical outcome, and survival pattern.
      MATERIALS AND METHODS: The study comprised cancer patients attending radiotherapy
      outdoor (November 2005 to June 2006). There were 104 patients of age >=60 years
      (elderly group) and 121 patients of 45-59 years (younger group). RESULTS: Elderly
      group had median age 65 years (60-88 years) with M:F = 1:1. The younger group had
      median age 50 years (45-59 years) with M:F = 1:2. Elderly had higher proportion
      of gastrointestinal and genito-urinary tract malignancies. Younger group had
      higher proportion of breast, lymphoma, and brain tumor. 13% had co-morbidity, 50%
      received treatment, 27% were treated with radiotherapy with or without surgery,
      and two-third of these cases belong to elderly group. Majority tolerated
      treatment well. 10% had significant grade of toxicity. 57% of elderly patients
      did not accept and one-fourth of all cases did not complete the prescribed
      treatment. 88% cases were responders of which 70% showed complete response. There
      were no differences between two groups. At 12 months 35% of treated patients came
      for follow-up. At first 12 months, 60-70% were alive without disease. CONCLUSION:
      There were differences between two groups in terms of performance status,
      treatment acceptance, and treatment modality prescribed. Elderly patients deserve
      same opportunity as younger patients for treatment and survival options from the
      oncologist.

PMID- 24455631
TI  - Keratocystic odontogenic tumor with mural calcification: A case report.

PMID- 24455632
TI  - Immunocompromised hosts: Infections and biomarkers.

PMID- 24455633
TI  - Temporal lobe atypical teratoid/ rhabdoid tumor in a 24-year old adult female.

PMID- 24455634
TI  - Cytodiagnosis of mucin-producing medullary carcinoma of the thyroid gland.

PMID- 24455635
TI  - Elizabethkingia meningoseptica bacteremia in immunocompromised hosts: The first
      case series from India.
AB  - BACKGROUND: Although Elizabethkingia meningoseptica (Chryseobacterium
      meningosepticum) infections in immunocompromised hosts have been recognised,
      clinical data detailing these infections remain limited, especially from India.
      Antimicrobial susceptibility data on E. meningoseptica remain very limited, with
      no established breakpoints by Clinical and Laboratory Standards Institute (CLSI).
      The organism is usually multidrug resistant to antibiotics usually prescribed for
      treating Gram-negative bacterial infections, a serious challenge to the patient
      and the treating clinicians. MATERIALS AND METHODS: The analysis was done in a
      tertiary care oncology and stem cell transplant center. Susceptibility testing
      and identification of E. meningoseptica was done using Vitek auto analyzer.
      Records of immunocompromised patients with E. meningoseptica bacteremia were
      analysed from January 2009 to March 2012. RESULTS: A total of 29 E.
      meningoseptica bacteremia cases were documented between 2009 and 2012. Eleven
      patients were immunocompromised. Three were post stem cell transplant and one was
      post cord blood transplant. The mean age of the patients was 48.4 years. Mean
      Charlson's comorbidity index was 5.7. Four had solid organ malignancies, five had
      hematological malignancies, and two had lymphoreticular malignancy. Eight
      patients had received chemotherapy. Mean Apache II score was 18. Mean Pitts score
      for bacteremia was 4.7. Two were neutropenic (one post SCT, one MDS post chemo)
      with a mean white blood cell (WBC) count of 450/mm(3) . Ten had a line at the
      time of bacteremia. Mean duration of the line prior to bacteremia was 8 days.
      Eight had line-related bacteremia. Three had pneumonia with secondary bacteremia.
      All received combination therapy with two or more antibiotics which included
      cotrimoxazole, rifampicin, piperacillin-tazobactam, tigecycline, or cefepime
      tazobactam. All the isolates showed in vitro resistance to ciprofloxacin. Five
      patients died, but a multivariate analysis was not done to calculate the
      attributable mortality. CONCLUSION: In our study, central line was the commonest
      risk factor for E. meningosepticum bacteremia, although a multivariate analysis
      was not done. There has not been much of a change in the susceptibility pattern
      of these organisms over 3 years, with good susceptibility to piperacillin
      tazobactam and cotrimoxazole. Even though uncommon, E. meningoseptica is an
      important pathogen, especially in immunocompromised hosts with indwelling
      devices.

PMID- 24455636
TI  - Procalcitonin and quantitative C-reactive protein role in the early diagnosis of
      sepsis in patients with febrile neutropenia.
AB  - BACKGROUND: Neutropenia with fever is a common syndrome in patients with
      hematologic malignancies who have a high risk of infectious diseases. As early
      diagnosis of infection in such patients is really important, the aim of this
      study was to investigate the sensitivity and specificity of procalcitonin (PCT)
      and C-reactive protein (CRP) in the diagnosis of sepsis in febrile neutropenic
      patients in a referral malignant care center of Isfahan in 2010-2011. MATERIALS
      AND METHODS: In this analytical cross-sectional study, all the febrile
      neutropenic patients who were admitted in the referral malignant care center in
      2010-2011 were evaluated. The data from every individual, including sex, age,
      admission time, and duration of fever before taking antibiotics were collected.
      Sixty-four subjects were involved in the study. Blood samples of the subjects
      were obtained and the levels of PCT, CRP, Absolute neutrophil count (ANC), and
      white blood cell count were measured, and blood cultures were obtained. According
      to the test results, the 64 subjects were divided into two groups including
      patients with sepsis and without sepsis. RESULTS: Mean value of PCT in the sepsis
      group was 28.65 +/- 2.68 and in the non-sepsis group was 2.48 +/- 0.66, with a P
      value of 0.000. In case of CRP, the sepsis group had a mean of 159.48 +/- 9.73
      and the non-sepsis group had a mean of 126.17 +/- 10.63 (P = 0.015). Sensitivity
      and specificity were analyzed by using receiver operating characteristic (ROC)
      curve and were found to be 92.5% and 97.3%, respectively, for PCT and 70.5% and
      42.1%, respectively, for CRP. CONCLUSION: PCT can be considered as a predictive
      factor and a diagnostic marker for the diagnosis of sepsis in febrile neutropenic
      patients.

PMID- 24455637
TI  - Life-threatening upper airway obstruction associated with prior radiotherapy.

PMID- 24455638
TI  - Numb chin syndrome as a manifestation of non-small cell lung cancer.

PMID- 24455639
TI  - Prognostic factors for mortality with fungal blood stream infections in patients
      with hematological and non-hematological malignancies.
AB  - BACKGROUND: This single center retrospective analysis was undertaken to identify
      the incidence, clinical impact, and prognostic factors for mortality associated
      with fungal blood stream infections (BSI) in cancer patients. MATERIALS AND
      METHODS: One hundred and twenty four patients had 169 episodes of fungal BSI.
      Incidence has not changed over a 10 year period but non albicans candida species
      are the predominant fungal isolates. Mortality with fungal BSI was significantly
      higher than that with other microbial agents. Risk of mortality was associated
      with renal dysfunction and Candida albicans as the isolate. Type of chemotherapy,
      patient characteristics, and neutrophil count did not influence the mortality
      following fungal BSI. CONCLUSION: Fungal BSI is rare and the incidence has not
      changed in this hospital. Mortality associated with fungal BSI is high. Risk
      score at the time of developing fungal BSI has prognostic potential to identify
      patients with higher risk of mortality associated with fungal BSI.

PMID- 24455640
TI  - Rectal cancer in Kashmir: Early steps in the right direction.

PMID- 24455641
TI  - Dumbbell-shaped neurofibroma of the upper thoracic spine: A case report.

PMID- 24455642
TI  - Carcinosarcoma thyroid: An unusual morphology with a review of the literature.

PMID- 24455643
TI  - Sphincter-saving surgeries for rectal cancer: A single center study from Kashmir.
AB  - SUMMARY AND BACKGROUND DATA: The goals in the treatment of rectal cancer are
      cure, local control, and preservation of sphincter, bladder and sexual function.
      Surgical resection using sharp mesorectal dissection is important for achieving
      these goals. OBJECTIVES: The current treatment of choice for carcinoma rectum is
      sphincter saving procedures, which have practically replaced the previously done
      abdominoperineal resection. We performed a study in our institute to evaluate the
      surgical outcome and complications of rectal cancer. MATERIALS AND METHODS: This
      prospectivestudy included 117 patients, treated for primary rectal cancer by low
      anterior resection (LAR) from May 2007 to December 2010. All patients underwent
      standard total mesorectal excision (TME) followed by restoration of continuity.
      RESULTS: The peri-operative mortality rate was 2.5% (3/117). Post-operative
      complications occurred in 32% of the patients. After a median follow up of 42
      months, local recurrences developed in 6 (5%) patients and distant metastasis in
      5 (4.2%). The survival rate was 93%. CONCLUSION: The concept of total mesorectal
      excision (TME), advances in stapling technology and neoadjuvant therapy have made
      it possible to preserve the anal sphincter in most of the patients. Rectal cancer
      needs to be managed especially in a specialized unit for better results.

PMID- 24455644
TI  - Hemangioma calcificans: A rare entity with epileptogenic potential.

PMID- 24455645
TI  - Primary pleuropulmonary synovial sarcoma: A report of two cases and review of
      literature.

PMID- 24455646
TI  - Dermatofibrosarcoma protuberans: Role of wide local excision.
AB  - OBJECTIVES: The main objective of the present study was to study the outcome of
      surgical treatment of dermatofibrosarcoma protuberans. MATERIALS AND METHODS:
      This study included 45 patients both retrospective and prospective from December
      1995 to December 2010. RESULTS: Out of 45 patients, 30 were males and 15 females
      with the male to female ratio of 2:1. Mean age of presentation was 38.4 + 13.2
      years. Commonest mode of presentation was raised firm multinodular lesion with
      fixity to overlying skin. Site distribution was 42.22% trunk, 57.88% extremities
      and head and neck. None of the patients had lymph node involvement All patients
      underwent wide local excision. On histological examination, 8 patients had
      positive margins. Overall recurrence rate was 22.22%. (please clarify what is the
      difference between the rate of recurrence following surgery and the overall
      recurrence rate) Only 2 patients developed metastasis to lungs in the course of
      their follow-up. Out of 45 patients, 35 remained recurrence free over a varying
      period of 5 months to 13 years (mean 68 months). Ten patients developed one or
      more local recurrences. Average time from initial treatment to recurrence was 32
      months. All patients with recurrent tumors were subjected to salvage treatment,
      i.e., re-excision. Average recurrence-free period was 36 + 44 months within a
      mean follow-up of 68 months. CONCLUSION: Because of the potential of local
      recurrence, therapy for DFSP should be directed toward adequate local excision of
      the primary lesion. Minimal resection should include a surrounding margin,
      comprising 3-cm margin of normal skin and removal of underlying deep fascia.
      Compromising on margins invites higher chances of local recurrence.

PMID- 24455647
TI  - Oncological safety of immediate rectus abdominis myocutaneous breast
      reconstruction in patients with locally advanced disease (stage IIb and III).
AB  - BACKGROUND: The management of locally advanced (Stage IIb and III) breast cancer
      is challenging. It often includes multimodal treatment with systemic therapy
      and/or radiation therapy and surgery. Immediate breast reconstruction has not
      traditionally been performed in these patients. We review the results of
      immediate rectus abdominis musculo-cutaneous (TRAM/VRAM) flap in 60 patients
      treated for Stage IIb and III breast cancer. MATERIALS AND METHODS: Data were
      collected prospectively on 60 patients diagnosed with Stage IIb (32 patients) and
      Stage III (28 patients) breast cancer between May 2008 and May 2012. All patients
      had mastectomy and immediate rectus abdominis myocutaneous reconstruction (TRAM
      in 40 patients and VRAM in 20 patients). All patients received primary systemic
      therapy, and all patients received postoperative radiotherapy to the operative
      site. RESULTS: Mean age was 40.13 (range 28-53) years, mean hospital stay was
      8.86 days and mean follow-up for the group was 28 months. Neither of them
      developed local disease recurrence in the operative site till the last follow-up.
      Eight (13.3%) patients had some delay in chemo-radiation therapy due to flap
      related complications. Flap-related complications were present in eight patients
      (partial flap failure in four and superficial skin necrosis in four). There was
      no adverse effect of chemo-radiation therapy on reconstructed breast. CONCLUSION:
      Immediate TRAM/VRAM breast reconstruction for locally advanced breast cancer is
      not associated with a significant delay in adjuvant therapy or an increased risk
      of local relapse. Radiation therapy can be delivered to the reconstructed breast
      when indicated without difficulty. Breast reconstruction facilitates surgical
      resection of locally advanced breast cancer with primary closure and should be
      considered if the patient desires immediate breast reconstruction.

PMID- 24455648
TI  - Is existing cervical cancer screening proven productive in developing nations:
      Time to move from the laboratory to community?

PMID- 24455649
TI  - Through the microscope: The correct diagnosis to decide a suitable therapy.

PMID- 24455650
TI  - Metastasis in central nervous system: Clinicopathological study with review of
      literature in a tertiary care center in South India.
AB  - BACKGROUND: Secondary central nervous system (CNS) tumors are common in Western
      countries, but in Indian literature, scant data are available. With the advent of
      newer imaging techniques, the confirmatory histopathological diagnosis has become
      comparatively easier. Hereby, we have analyzed our data from a single tertiary
      care center in south India. MATERIALS AND METHODS: In this retrospective study
      from January 2000 to December 2010, histopathologically diagnosed secondary CNS
      tumors were reviewed along with clinical, imaging, and relevant
      immunohistochemical findings. Meningeal, lymphoproliferative, and
      myeloproliferative tumors and autopsy data were not included in the study group.
      RESULTS: There were 40 secondary CNS tumors. Male to female ratio was 2.3:1. Age
      range was wide (28-75 years). Majority of cases were seen in the fourth and fifth
      decade. Imaging-wise, (computed tomography and magnetic resonance imaging)
      majority were single lesions (n = 34, 85%). Most commonly, these single lesions
      were present in the cerebral hemisphere (n = 20, 50%) followed by cerebellum (n =
      10, 25%). Adenocarcinoma accounted for maximum number of cases (n = 25, 62.5%)
      with lungs being the most common primary. CONCLUSION: We have noted 25%
      metastatic adenocarcinomas in cerebellar location, which is higher when compared
      with available world literature. However, we also encountered a good number of
      cases (30%) due to unknown primary. Though histopathological examination with use
      of immunohistochemical markers can reliably distinguish primary from secondary
      CNS tumors in addition to available clinical and imaging data, particularly in
      developing countries, still a better work-up with an array of immunohistochemical
      markers and newer imaging modalities is desirable.

PMID- 24455651
TI  - Pattern of salivary gland tumors in Manipur, India: A 10 year study.
AB  - BACKGROUND: Salivary gland lesions, especially the neoplastic lesions constitute
      a highly heterogeneous histopathologic group. Several studies have reported a
      significant difference in the global distribution of salivary gland tumors, but
      no formal study has been carried out in this part of the globe. OBJECTIVES: To
      document the pattern of various salivary gland tumors in Manipur, a state in
      North Eastern India. MATERIALS AND METHODS: This is a 10 years (2002-2011)
      retrospective study of all salivary gland specimens received at our referral
      teaching hospital in Manipur, India. All the histopathology slides of salivary
      gland specimens during the study period were reviewed and clinical details were
      obtained from the archives. Restaining of slides and fresh sections of tissue
      blocks were performed whenever required. Data thus collected were analyzed.
      RESULTS: A total of 104 cases of salivary gland lesions were studied during the
      study period. Age ranged from 5 years to 78 years with an overall slight female
      preponderance (M:F = 1:1.08). Parotid (56.65%) was the commonest gland involved
      followed by submandibular gland (31.73%).Neoplastic lesions comprised of 78 (75%)
      cases and non-neoplastic lesions constituted 25% (26 cases). Among the neoplastic
      lesions, benign lesions (53.85%) predominated over malignant lesions (21.15%).
      Pleomorphic adenoma was the commonest benign neoplastic lesion and mucoepidermoid
      carcinoma was the commonest malignant tumor. Chronic sialadenitis was the
      predominant lesion in the non-neoplastic group. CONCLUSION: The principal site
      for salivary gland tumors was the parotid gland and pleomorphic adenoma
      outnumbered all the other tumors. Females are more affected in the malignant
      group.

PMID- 24455652
TI  - Immunohistochemistry: A diagnostic aid in differentiating primary epithelial
      ovarian tumors and tumors metastatic to the ovary.
AB  - INTRODUCTION: Among cancers of the female genital tract, the incidence of ovarian
      cancer ranks below only carcinoma of the cervix and the endometrium. Recent years
      have witnessed significant development in the use of immunohistochemistry in
      diagnostic ovarian pathology. MATERIALS AND METHODS: We received 95 specimens and
      biopsies of primary ovarian neoplasms and neoplasms metastatic to the ovary in a
      period of 2 years. Of these 30 cases were of the primary surface epithelial
      neoplasms and seven of metastatic tumors. DISCUSSION: The most common tumors
      metastasizing to the ovary originate from the gastrointestinal tract followed by
      the endometrium. We used a panel of six markers including cytokeratin-7 (CK7),
      CK20, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), estrogen
      receptor (ER) and Wilms' tumor 1 (WT1) to help classify various surface
      epithelial tumors as well as to differentiate them from tumors metastatic to the
      ovary. CONCLUSION: CK7 is the most helpful marker to differentiate primary
      ovarian carcinoma from metastatic colorectal carcinoma of the ovary. Nearly, 96%
      of ovarian adenocarcinomas were positive for CK7 in contrast to metastatic
      colorectal, which showed only 25% positivity. We also found that CK7, CK20 and
      CEA are useful markers to differentiate primary serous tumors from primary
      mucinous tumors; however, these are less helpful in differentiating ovarian
      mucinous adenocarcinomas from colorectal adenocarcinomas metastasizing to the
      ovaries. WT1 helps in typing primary surface epithelial tumors of the ovary and
      is also significant in determining whether a serous carcinoma within the ovary is
      primary or metastatic.

PMID- 24455653
TI  - Chronic myeloid leukemia in India: The poster child of translational medicine
      needs help!

PMID- 24455654
TI  - Chronic myeloid leukemia in children and adolescents: A single center experience
      from Eastern India.
AB  - CONTEXT: Chronic Myeloid Leukemia (CML) constitutes around 3% of leukemia in the
      children and adolescent age group. AIMS: The aim of the study was to evaluate the
      characteristics at presentation and the treatment outcome of CML in the children
      and adolescent age group. SETTINGS AND DESIGN: Retrospective analysis was carried
      out at a single center in India. MATERIALS AND METHODS: Thirteen patients (<=17
      years) attending CML outdoor from April 2008 to August 2012 were included in the
      analysis. STATISTICAL ANALYSIS USED: The mean and median of various parameters
      were calculated using a Microsoft excel sheet. SPSS 16.0 version software was
      used to calculate OS and PFS. RESULTS: CML-CP was the most common phase at
      presentation. Maximum patients belonged to the 14 - 17 year old age group.
      Disease was common in the male sex. Splenic discomfort and asthenia were the most
      common symptoms and splenomegaly was the most common sign. CONCLUSIONS: The
      treatment with Imatinib was effective and well-tolerated.

PMID- 24455655
TI  - Challenges in optimizing chemoradiation in locally advanced non small-cell lung
      cancers in India.
AB  - Data supporting use of concurrent chemoradiation in locally advanced lung cancers
      comes from clinical trials from developed countries. Applicability and outcomes
      of such schedules in developing countries is not widely reported. There are
      various challenges in delivering chemoradiation in locally advanced non small
      cell lung cancer in developing countries which is highlighted by an audit of
      patients treated with chemoradiation in our center. This article deals with the
      challenges in the context of a developing country. We conclude that sequential
      chemoradiotherapy is better tolerated than concurrent chemoradiation in Indian
      patients with locally advanced non-small cell lung cancers. Patients with stage
      IIIa, normal weight or overweight, and adequate baseline pulmonary function
      should be offered concurrent chemoradiation. 

PMID- 24455658
TI  - Confusion worse confounded.

PMID- 24455656
TI  - Denosumab: A comprehensive review.
AB  - The clinical sequelae from bone metastases, termed skeletal-related events
      (SREs), are among the most frequent and debilitating complications in patients
      with advanced cancer. Bone metastases are characterized by pathologically
      increased osteoclast activity, and accumulating evidence indicates that tumor
      cells interact within the bone to stimulate the receptor activator of nuclear
      factor kB (RANK)-RANK ligand (RANKL) pathway. RANKL is an essential mediator of
      osteoclast formation, function, and survival. Because of the central role of
      RANKL in cancer-induced bone destruction, the inhibition of RANKL has the
      potential to result in the reduction of pathologic bone resorption. Denosumab is
      a fully human monoclonal antibody specific for RANKL that inhibits the formation,
      activation, and survival of osteoclasts. This in turn decreases bone resorption
      and reduces cancer-induced bone destruction. In this review, we give an overview
      of the drug Denosumab with its history, mechanism of action, clinical trial data,
      adverse effects, and future challenges. 

PMID- 24455659
TI  - Comprehensive update on cancer scenario of Bangladesh.
AB  - Bangladesh, at 142 million people, is the ninth most populous country in the
      world. There are 13 to 15 lakh cancer patients in Bangladesh, with about two lakh
      patients newly diagnosed with cancer each year. As an overview, lung cancer and
      mouth-oropharynx cancer rank as the top two prevalent cancers in males. Other
      types of cancers are esophagus cancer and stomach cancer. In women, cancer cervix
      uteri and breast cancer are most prevalent. Other cancer types, which affect
      women, are mouth and oropharynx cancer, lung cancer, and esophagus cancer. There
      are around 150 qualified clinical oncologists and 16 pediatric oncologists
      working in the different parts of the country. Regular cancer treatment is
      available in 19 hospitals and 465 hospital beds are attached as indoor or day
      care facilities for chemotherapy in the oncology/radiotherapy departments. There
      are about 15 linear accelerators, 12 Co-60 teletherapy and 12 brachytherapy units
      currently available. Approximately, 56 cancer chemotherapeutic agents are
      obtainable in Bangladesh. Research facilities are available at tertiary care
      centers and a few multi country collaborative research activities are ongoing.
      Bangladesh has a unique National Cancer Control Strategy and Plan of Action 2009
      2015 formulated with the assistance of WHO with an objective to develop and
      implement continuum of cancer care through a comprehensive cancer control
      programe. Preventive measures taken to reduce the incidence of cancer include
      reduced tobacco smoking, change of dietary habit and reduced food adulteration,
      ensuring reproductive hygiene, increased physical activity, and reduced
      occupational hazard. Awareness buildup and media campaign are going on by
      organizing the general people, opinion leaders of the society, and boy and girl
      scout. Training of general physicians on cancer warning signs and setup of early
      cancer detection centers at each medical college and district levels are ongoing.
      Beside these, some other major cancer programs have taken place for early
      detection of breast, cervical and oral cancer by Bangladesh Government and NGOs
      such as ICDDR'B, BRAC, Ahsania Mission Cancer Hospital, BSMMU, Bangladesh Cancer
      Society, Ashic Foundation, Amader Gram, AK Khan Healthcare Trust, CANSUP,
      Oncology club etc. Piloting of cervical cancer vaccination has recently been
      completed. Improving the cancer scenario overnight is not an easy task but policy
      makers may become interested and push this agenda forward, if the huge health
      impact and economic loss caused by cancer become evident to them. Besides,
      Bangladesh has accepted reduction of cancer morbidity and mortality targets set
      by United Nations and World Health Organization as a part of global non
      communicable disease prevention agreement. 

PMID- 24455660
TI  - Angelina's choice.
AB  - This is an opinion piece on how a celebrity's personal choice to undergo
      prophylactic mastectomy on discovery of an aberrant gene, when publicly promoted,
      carries in itself the power to influence and impact healthcare trends and
      decisions. When celebrities advocate causes that are universally and uniformly
      acceptable and indisputable as the best in the realm of healthcare and cure (e.g.
      no smoking), it creates well-being and awareness in society at large. But those
      which are personal choices made out of a repertoire of other available and
      effective options may, because of celebrity preference, don the mantle of a norm.
      They thus run the danger of being blindly replicated by others without proper
      awareness and knowledge of the true potential of disease, risk factors, and other
      existing remedial or risk-reducing measures. Society should thus be encouraged to
      question, debate, and understand the validity, authenticity, and reason of the
      choices, especially those with a medical basis. This tempering of information
      with intelligence and rationale and making informed choices based on facts will
      serve humanity as a whole. 

PMID- 24455661
TI  - Pseudo Chediak Higashi-like inclusions in myeloblasts in AML-M2.

PMID- 24455662
TI  - Primary skull lymphoma: A case report and review of similar cases.

PMID- 24455663
TI  - Be a true listener, rather than a good conversationalist.
AB  - Oncology patient care is an ever evolving field both as a science and a clinical
      art. We evaluate, diagnose, and treat cancer patients daily. We break the bad and
      the good news to them. We are the hope on which their life and dreams hang on.
      We, as practitioners, have to assess each patient as an intelligent observer. We
      have to devise our strategy to break heartbreaking news to them in a tailored and
      personalized fashion according to the physical, psychological, emotional, and
      social status of the patient. The process has to be gentle, perceptive,
      pragmatic, yet truthful. These need to be reasonably good observational,
      listening, comprehending, and delivering potentials; which are sharpened by
      experience and skills. 

PMID- 24455665
TI  - Colloid carcinoma of the intestinal type in the uterine cervix.

PMID- 24455664
TI  - Clinical challenges: Myeloma and concomitant type 2 diabetes.
AB  - Multiple myeloma is a malignant plasma cell disorder that accounts for
      approximately 10% of all hematological cancers. It is characterized by
      accumulation of clonal plasma cells, predominantly in the bone marrow. The
      prevalence of type 2 diabetes is increasing; therefore, it is expected that there
      will be an increase in the diagnosis of multiple myeloma with concomitant
      diabetes mellitus. The treatment of multiple myeloma and diabetes mellitus is
      multifaceted. The coexistence of the two conditions in a patient forms a major
      challenge for physicians. 

PMID- 24455666
TI  - Should the Genitoplasty of Girls with CAH be Done in One or Two Stages?

PMID- 24455667
TI  - School environment and school injuries.
AB  - BACKGROUND: Although injuries at school are an important issue in public health,
      environmental factors in schools and school yards have seldom been the focus of
      school injury research. The goal of our investigation was to examine the effect
      of environmental factors on school injuries. METHODS: Nine comprehensive Finnish
      schools registered school injuries over a period of two school years. Injuries
      were classified as being associated with environmental factors, suspected
      environmental factors, and others. The consensus between two independent
      classifiers was 81%. RESULTS: A total of 722 injuries were classified. In 11.6%
      of these injuries, the physical environment factor was evident, and in 28.1% of
      the injuries, physical environment was suspected of being a contributory risk
      factor. Thus the physical environment of the school was a contributing factor in
      over a third (39.7%) of injuries occurring in the school, on the school yard or
      during the journey to, or from school. In this study, conducted in Finland, ice
      on the ground was mentioned most frequently as an environmental risk factor.
      CONCLUSION: In Finland, the Nordic weather conditions are not taken into account
      in the school yard and playground plans as they ought to from the safety point of
      view. An initiative has been launched on a mandatory wintertime master plan for
      every school yard.

PMID- 24455668
TI  - Assessment of cytotoxicity, fetotoxicity, and teratogenicity of Plathymenia
      reticulata Benth Barks aqueous extract.
AB  - Scientific assessment of harmful interactions of chemicals over the entire
      reproductive cycle are divided into three segments based on the period: from
      premating and mating to implantation (I), from implantation to major
      organogenesis (II), and late pregnancy and postnatal development (III). We
      combined the segments I and II to assess Plathymenia reticulata aqueous extract
      safety. In order to investigate reproductive toxicity (segment I), pregnant rats
      received orally 0.5 or 1.0 g/kg of extract, daily, during 18 days. These
      concentrations were determined by a preliminary in vitro LD50 test in CHO-k1
      cells. A control group received deionized water. The offspring was removed at the
      19th day, by caesarean, and a teratology study (segment II) was carried out. The
      corpora lutea, implants, resorptions, live, and dead fetuses were then counted.
      Placenta and fetuses were weighted. External and visceral morphology were
      provided by the fixation of fetuses in Bouin, whereas skeletal analysis was
      carried out on the diaphanizated ones. The increase in the weights of placenta
      and fetuses was the only abnormality observed. Since there was no sign of
      alteration on reproduction parameters at our experimental conditions, we conclude
      that P. reticulata aqueous extract is safe at 0.5 to 1.0 g/kg and is not
      considered teratogenic.

PMID- 24455669
TI  - Engineered hypopharynx from coculture of epithelial cells and fibroblasts using
      poly(ester urethane) as substratum.
AB  - Porous polymeric scaffolds have been much investigated and applied in the field
      of tissue engineering research. Poly(ester urethane) (PEU) scaffolds, comprising
      pores of 1-20  MU m in diameter on one surface and >= 200 MU m on the opposite
      surface and in bulk, were fabricated using phase separation method for
      hypopharyngeal tissue engineering. The scaffolds were grafted with silk fibroin
      (SF) generated from natural silkworm cocoon to enhance the scaffold's
      hydrophilicity and further improve cytocompatibility to both primary epithelial
      cells (ECs) and fibroblasts of human hypopharynx tissue. Coculture of ECs and
      fibroblasts was conducted on the SF-grafted PEU scaffold (PEU-SF) to evaluate its
      in vitro cytocompatibility. After co-culture for 14 days, ECs were lined on the
      scaffold surface while fibroblasts were distributed in scaffold bulk. The results
      of in vivo investigation showed that PEU porous scaffold possessed good
      biocompatibility after it was grafted by silk fibroin. SF grafting improved the
      cell/tissue infiltration into scaffold bulk. Thus, PEU-SF porous scaffold is
      expected to be a good candidate to support the hypopharynx regeneration.

PMID- 24455670
TI  - Impact of pregnancy on zonisamide pharmacokinetics in rabbits.
AB  - Pregnancy is associated with various physiological changes which may lead to
      significant alterations in the pharmacokinetics of many drugs. The present study
      was aimed to investigate the potential effects of pregnancy on the
      pharmacokinetic profile of zonisamide (ZNM) in the rabbit. Seven female rabbits
      were used in this study. The pregnant and nonpregnant rabbits received ZNM orally
      at a dose of 10 mg/kg and blood samples were collected from the animals just
      before receiving the drug and then serially for up to 24 h. The plasma samples
      were analyzed using tandem mass spectrometric method. Following a single oral
      dose of ZNM to the rabbits, the mean values of ZNM plasma concentrations at
      different times were consistently low in pregnant compared to nonpregnant
      rabbits. The mean values of ZNM's Cmax and AUC0-infinity were significantly (P <
      0.05) decreased, whereas the CL/F exhibited substantial increase (P < 0.05) in
      pregnant compared to nonpregnant rabbits. Tmax, t1/2abs, t1/2el, MRT, and Vd/F
      showed no significant differences between the two groups. The present study
      demonstrates that pregnancy decreased ZNM plasma concentrations in rabbits and
      that the decrease could be due to decreased extent of gastrointestinal
      absorption, induced hepatic metabolism, or enhanced renal elimination of the
      drug.

PMID- 24455671
TI  - The uptake mechanism of Cd(II), Cr(VI), Cu(II), Pb(II), and Zn(II) by mycelia and
      fruiting bodies of Galerina vittiformis.
AB  - Optimum concentrations of heavy metals like copper, cadmium, lead, chromium, and
      zinc in soil are essential in carrying out various cellular activities in minimum
      concentrations and hence help in sustaining all life forms, although higher
      concentration of these metals is lethal to most of the life forms. Galerina
      vittiformis, a macrofungus, was found to accumulate these heavy metals into its
      fleshy fruiting body in the order Pb(II) > Cd(II) > Cu(II) > Zn(II) > Cr(VI) from
      50 mg/kg soil. It possesses various ranges of potential cellular mechanisms that
      may be involved in detoxification of heavy metals and thus increases its
      tolerance to heavy metal stress, mainly by producing organic acids and
      phytochelatins (PCs). These components help in repairing stress damaged proteins
      and compartmentalisation of metals to vacuoles. The stress tolerance mechanism
      can be deduced by various analytical tools like SEM-EDX, FTIR, and LC-MS.
      Production of two kinds of phytochelatins was observed in the organism in
      response to metal stress.

PMID- 24455672
TI  - Effect of complexation with arabinogalactan on pharmacokinetics of "guest" drugs
      in rats: for example, warfarin.
AB  - A pharmacokinetic study of the warfarin (WF) : arabinogalactan (AG) complex with
      the 1 : 10 mass ratio after its intragastric introduction to Wistar rats at a
      dose of 5 mg/kg (WF dose in the complex was 0.5 mg/kg) once a day for three days
      was conducted. It was found that Cmax, T1/2, and AUC of WF in the complex form
      were lower than after the introduction of blank WF at the same dose, but its
      elimination (Cl, MRT) was much faster. Significant accumulation (C(min)) and an
      abrupt increase in plasma concentration after the third introduction were
      observed for blank WF, whereas the complex showed a much more moderate increase
      in concentration at this point. However, despite obvious differences in
      pharmacokinetic parameters, the efficacies of both agents were virtually
      identical; the complex differed from blank WF by only 15%. This value is rather
      insignificant and does not impair its anticoagulant activity. Thus, we can
      conclude that introduction of the WF : AG complex is safe in terms of reduction
      of the bleeding risk and accumulation.

PMID- 24455673
TI  - Safety evaluation of turmeric polysaccharide extract: assessment of mutagenicity
      and acute oral toxicity.
AB  - Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used
      for centuries as a spice and household remedy. The present study was carried out
      to assess the possible mutagenic potential and acute oral toxicity of
      polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The
      standard battery of in vitro genotoxicity tests, bacterial reverse mutation test
      (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to
      assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results
      showed no mutagenic effect with NR-INF-02 up to a dose of 5000 ug/mL in BRMT. The
      results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in
      a dose range of 250.36 to 2500 ug/mL with and without metabolic activation (S9).
      In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body
      weight in Wistar rats. Overall, results indicated that polysaccharide extract of
      C. longa was found to be genotoxically safe and also exhibited maximum tolerable
      dose of more than 5 g/kg rat body weight.

PMID- 24455674
TI  - Genetic structure and preliminary findings of cryptic diversity of the Malaysian
      Mahseer (Tor tambroides Valenciennes: Cyprinidae) inferred from mitochondrial DNA
      and microsatellite analyses.
AB  - This study examines the population genetic structure of Tor tambroides, an
      important freshwater fish species in Malaysia, using fifteen polymorphic
      microsatellite loci and sequencing of 464 base pairs of the mitochondrial
      cytochrome c oxidase I (COI) gene. A total of 152 mahseer samples were collected
      from eight populations throughout the Malaysia river system. Microsatellites
      results found high levels of intrapopulation variations, but mitochondrial COI
      results found high levels of interpopulations differentiation. The possible
      reasons for their discrepancies might be the varying influence of genetic drift
      on each marker or the small sample sizes used in most of the populations. The
      Kelantan population showed very low levels of genetic variations using both
      mitochondrial and microsatellite analyses. Phylogenetic analysis of the COI gene
      found a unique haplotype (ER8*), possibly representing a cryptic lineage of T.
      douronensis, from the Endau-Rompin population. Nevertheless, the inclusion of
      nuclear microsatellite analyses could not fully resolve the genetic identity of
      haplotype ER8* in the present study. Overall, the findings showed a serious need
      for more comprehensive and larger scale samplings, especially in remote river
      systems, in combination with molecular analyses using multiple markers, in order
      to discover more cryptic lineages or undescribed "genetic species" of mahseer. 

PMID- 24455675
TI  - Short communication: subtyping of Mycobacterium kansasii by PCR-restriction
      enzyme analysis of the hsp65 gene.
AB  - Mycobacterium kansasii is one of the most common causes of pulmonary disease
      resulting from nontuberculous mycobacteria (NTM). It is also the most frequently
      isolated NTM species from clinical specimens in Poland. The aim of this study was
      to investigate the distribution of M. kansasii subtypes among patients suspected
      of having pulmonary NTM disease. Fifty clinical isolates of M. kansasii recovered
      from as many patients with suspected mycobacterial lung disease between 2000 and
      2010 in Poland were genotyped by PCR-restriction enzyme analysis (PCR-REA) of
      partial hsp65 gene. Mycobacterium kansasii subtype I was the only genotype to be
      identified among the isolates, both disease-associated and non-disease
      associated. Isolation of M. kansasii subtype I from clinical specimens may be
      indicative of infection but may also merely represent colonization. 

PMID- 24455676
TI  - Protective effect of Thunbergia laurifolia (Linn.) on lead induced
      acetylcholinesterase dysfunction and cognitive impairment in mice.
AB  - Thunbergia laurifolia (linn., TL), a natural phenolic compound, has been reported
      to have many benefits and medicinal properties. The current study ascertains the
      total phenolic content present in TL aqueous leaf extract and also examines the
      antioxidant ability of the extract in preserving acetylcholinesterase (AChE)
      activity of mice exposed to lead in vivo and in vitro model. Mice were given lead
      acetate (Pb) in drinking water (1 g/L) together with TL 100 and 200 mg/kg/day.
      The result showed that Pb induced AChE dysfunction in both in vitro and in vivo
      studies. TL significantly prevented Pb induced neurotoxicity in a dose-dependent
      manner which was indicated by comparatively better performance of TL treated mice
      in Morris Water Maze Swimming Test and increased AChE activity in the tissue
      sample collected from the brains of these mice. TL also exhibited the greatest
      amount of phenolic content, which has a significant positive correlation with its
      antioxidant capacity (P < 0.05). Taken together, these data suggested that the
      total phenolic compounds in TL could exhibit antioxidant and in part
      neuroprotective properties. It may play a potential treatment strategy for Pb
      contamination.

PMID- 24455677
TI  - Targeting brain metastases in patients with melanoma.
AB  - Patients with brain metastases from malignant melanoma historically have a very
      poor outcome. Surgery and radiotherapy can be used, but for the majority of
      patients the disease will progress quickly. In the recent past, patients with
      brain metastases derived only minimal benefit from cytotoxic chemotherapy. Novel
      therapies that have been shown to be superior to chemotherapy in metastatic
      melanoma have made their way in clinic and data regarding their use in patients
      with treated or untreated brain metastases are encouraging. In this paper we
      describe the use of vemurafenib, dabrafenib, and ipilimumab in patients with
      melanoma disseminated to the brain in addition to other treatments currently in
      development. 

PMID- 24455678
TI  - The usefulness of clinical-practice-based laboratory data in facilitating the
      diagnosis of dengue illness.
AB  - Alertness to dengue and making a timely diagnosis is extremely important in the
      treatment of dengue and containment of dengue epidemics. We evaluated the
      complementary role of clinical-practice-based laboratory data in facilitating
      suspicion/diagnosis of dengue. One hundred overall dengue (57 dengue fever [DF]
      and 43 dengue hemorrhagic fever [DHF]) cases and another 100 nondengue cases (78
      viral infections other than dengue, 6 bacterial sepsis, and 16 miscellaneous
      diseases) were analyzed. We separately compared individual laboratory variables
      (platelet count [PC] , prothrombin time [PT], activated partial thromboplastin
      time [APTT], alanine aminotransferase [ALT], and aspartate aminotransferase
      [AST]) and varied combined variables of DF and/or DHF cases with the
      corresponding ones of nondengue cases. The sensitivity, specificity, accuracy,
      positive predictive value (PPV), and negative predictive value (NPV) in the
      diagnosis of DF and/or DHF were measured based on these laboratory variables.
      While trade-off between sensitivity and specificity, and/or suboptimal PPV/NPV
      was found at measurements using these variables, prolonged APTT + normal PT + PC
      < 100 * 10(9) cells/L had a favorable sensitivity, specificity, PPV, and NPV in
      diagnosis of DF and/or DHF. In conclusion, these data suggested that prolonged
      APTT + normal PT + PC < 100 * 10(9) cells/L is useful in evaluating the
      likelihood of DF and/or DHF. 

PMID- 24455679
TI  - Protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis
      and spatial learning and memory deficits in a rat model of vascular dementia.
AB  - Vascular dementia (VaD) is a common age-related neurodegenerative disease
      resulting from chronic hypoxia. In the present study, we examined the protective
      effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial
      learning and memory deficits in a chronic hypoperfusion rat model of VaD
      established by permanent bilateral carotid occlusion (2-VO). Sixty rats were
      randomly divided into sham-operated, VaD model, and VaD plus SB202190 groups (n =
      20/group). After sham/2-VO surgery, rats were administered 0.1% DMSO (sham
      operated and VaD groups) or SB202190 by intracerebroventricular injection. One
      week after inhibitor/vehicle treatment, hippocampal p38 MAPK phosphorylation was
      higher in the model group than in the SB202190 group (P < 0.01). Compared to the
      model group, the SB202190 group exhibited significantly shorter escape latencies
      in the Morris water maze hidden platform trials (P < 0.01) and longer times in
      the original platform quadrant during probe trials (P < 0.01). The SB202190 group
      also showed significantly reduced neuronal apoptosis in the hippocampus compared
      to VaD model rats (P < 0.01) as well as higher (antiapoptotic) Bcl-2 expression
      and lower (proapoptotic) caspase-3 expression (P < 0.01 for both). In conclusion,
      blockade of the p38 MAPK signaling pathway by SB202190 following permanent 2-OV
      reduced apoptosis of hippocampal neurons and rescued spatial learning and memory
      deficits. 

PMID- 24455680
TI  - Changes in the mucus barrier during cisplatin-induced intestinal mucositis in
      rats.
AB  - AIM: Gastrointestinal mucositis is a frequent complication of antineoplastic
      chemotherapy, but the effects of chemotherapy on mucosal defense mechanisms
      remain poorly understood. We studied the effects of cisplatin on mucin, one of
      the principal defense factors of the gastrointestinal mucosa, and evaluated the
      efficacy of two different types of H2-receptor antagonists against cisplatin
      induced mucositis. METHODS: Cisplatin (6 mg/kg) was administered intravenously to
      rats (day 0). The rats were sacrificed 1, 3, 7, and 11 days after treatment, and
      their stomach, jejunum, ileum, and colon were removed. Immunoreactivity of the
      mucosa was compared with the use of anti-mucin monoclonal antibody. To evaluate
      the efficacy of H2-receptor antagonists, either famotidine (3 mg/kg) or
      lafutidine (30 mg/kg) was given orally once daily on days 0, 1, and 2.
      Histological and biochemical findings were compared among the groups to assess
      effects on cisplatin-induced injury. RESULTS: Cisplatin significantly altered the
      immunoreactivity and content of mucin in the small intestinal mucosa, especially
      in the ileum. Lafutidine protected against cisplatin-induced mucosal injury and
      attenuated decreased mucin accumulation. CONCLUSION: Cisplatin appears to alter
      the mucus barrier function in the intestinal mucosa. Lafutidine might effectively
      prevent chemotherapy-induced mucositis by activating intestinal mucus cells.

PMID- 24455681
TI  - Antibacterial activity of nanocomposites of copper and cellulose.
AB  - The design of cheap and safe antibacterial materials for widespread use has been
      a challenge in materials science. The use of copper nanostructures combined with
      abundant biopolymers such as cellulose offers a potential approach to achieve
      such materials though this has been less investigated as compared to other
      composites. Here, nanocomposites comprising copper nanofillers in cellulose
      matrices have been prepared by in situ and ex situ methods. Two cellulose
      matrices (vegetable and bacterial) were investigated together with morphological
      distinct copper particulates (nanoparticles and nanowires). A study on the
      antibacterial activity of these nanocomposites was carried out for Staphylococcus
      aureus and Klebsiella pneumoniae, as pathogen microorganisms. The results showed
      that the chemical nature and morphology of the nanofillers have great effect on
      the antibacterial activity, with an increase in the antibacterial activity with
      increasing copper content in the composites. The cellulosic matrices also show an
      effect on the antibacterial efficiency of the nanocomposites, with vegetal
      cellulose fibers acting as the most effective substrate. Regarding the results
      obtained, we anticipate the development of new approaches to prepare
      cellulose/copper based nanocomposites thereby producing a wide range of
      interesting antibacterial materials with potential use in diverse applications
      such as packaging or paper coatings. 

PMID- 24455682
TI  - Efficacy of triptolide for children with moderately severe Henoch-Schonlein
      purpura nephritis presenting with nephrotic range proteinuria: a prospective and
      controlled study in China.
AB  - OBJECTIVE: To observe the clinical efficacy of the Chinese herb, Triptolide, in
      children with moderately severe Henoch-Schonlein purpura nephritis (HSPN).
      METHODS: From January 2007 to December 2011, 56 HSPN children manifested by
      nephrotic range proteinuria with normal kidney function and <50% crescents or
      sclerosing lesions on biopsy were hospitalized in the Children's Hospital of
      Zhejiang University School of Medicine. They were divided into two groups: the
      treatment group (n = 42; Triptolide at a dosage of 1 mg/kg . d, combined with
      prednisone at a dosage of 2 mg/kg . d, within a course of medium-to-long-term
      therapy of 6 to 9 months) and the control group (n = 14; prednisone alone, with
      the same procedure). RESULTS: Short-term remission was observed in 95% of
      patients from treatment group and in 72% of patients from control group,
      respectively. There was a significant difference between both groups (chi(2) =
      6.222, P = 0.029) for short-term effects. Meanwhile, no significant difference,
      as proteinuria, hematuria, hypertension, and decreased eGFR, was observed between
      the two groups in long-term followup (chi(2) = 3.111, P = 0.097). The Kaplan
      Meier plot analysis also revealed no significant difference (chi(2) = 2.633, P =
      0.105). CONCLUSION: Triptolide is effective in relieving short-term symptoms for
      moderately severe HSPN children, though its long-term effects need to be observed
      further.

PMID- 24455683
TI  - Clinical significance of AFP and PIVKA-II responses for monitoring treatment
      outcomes and predicting prognosis in patients with hepatocellular carcinoma.
AB  - AIM: Recently, the utility of tumor markers in the hepatocellular carcinoma (HCC)
      field has received a good deal of attention. Here, we review and summarize the
      results of studies on the roles played by the alpha -fetoprotein (AFP) and
      prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II)
      responses in terms of the monitoring of outcomes and prediction of prognosis
      after various HCC treatments. METHODS: Studies lodged in PUBMED and that
      satisfied our inclusion criteria were reviewed. RESULTS: We reviewed 12 studies
      measuring both AFP and PIVKA-II responses in HCC patients treated in various
      ways. The results are presented by treatment modality. CONCLUSION: Measurement of
      AFP and PIVKA II marker levels before and after HCC treatment is clinically
      useful in monitoring of treatment outcomes and prognosis and in predicting
      recurrence and survival.

PMID- 24455684
TI  - Stat3 upregulates leucine-rich repeat-containing g protein-coupled receptor 4
      expression in osteosarcoma cells.
AB  - The activation of signal transducer and activator of transcription 3 (Stat3)
      signaling is the common hallmark in various human cancers including osteosarcoma.
      In the present study, according to PCR-based microarrays using cDNA prepared from
      interleukin-6 (IL-6) treated osteosarcoma cells, we found that leucine-rich
      repeat-containing G protein-coupled receptor 4 (LGR4) was a transcriptional
      target of Stat3. Overexpression of Stat3 promoted LGR4 expression, while its
      deficiency using small interfering RNA (siRNA) reduced LGR4 expression.
      Furthermore, we identified a Stat3 binding motif located at -556 to -549 bp in
      the LGR4 promoter that is able to interact with Stat3. Thus, our results suggest
      a previously unknown Stat3-LGR4 molecular network, which may control osteosarcoma
      development and progression.

PMID- 24455686
TI  - In vitro and in vivo antimalarial evaluations of myrtle extract, a plant
      traditionally used for treatment of parasitic disorders.
AB  - Based on the collected ethnobotanical data from the Traditional Medicine and
      Materia Medica Research Center (TMRC), Iran, Myrtus communis L. (myrtle) was
      selected for the assessment of in vitro and in vivo antimalarial and cytotoxic
      activities. Methanolic extract of myrtle was prepared from the aerial parts and
      assessed for antiplasmodial activity, using the parasite lactate dehydrogenase
      (pLDH) assay against chloroquine-resistant (K1) and chloroquine-sensitive (3D7)
      strains of Plasmodium falciparum. The 4-day suppressive test was employed to
      determine the parasitemia suppression of the myrtle extract against P. berghei in
      vivo. The IC50 values of myrtle extract were 35.44 ug/ml against K1 and 0.87
      ug/ml against 3D7. Myrtle extract showed a significant suppression of
      parasitaemia (84.8 +/- 1.1% at 10 mg/kg/day) in mice infected with P. berghei
      after 4 days of treatment. Cytotoxic activity was carried out against mammalian
      cell lines using methyl thiazol tetrazolium (MTT) assay. No cytotoxic effect on
      mammalian cell lines up to 100 ug/mL was shown. The results support the
      traditional use of myrtle in malaria. Phytochemical investigation and
      understanding the mechanism of action would be in our upcoming project.

PMID- 24455685
TI  - Preparative purification of recombinant proteins: current status and future
      trends.
AB  - Advances in fermentation technologies have resulted in the production of
      increased yields of proteins of economic, biopharmaceutical, and medicinal
      importance. Consequently, there is an absolute requirement for the development of
      rapid, cost-effective methodologies which facilitate the purification of such
      products in the absence of contaminants, such as superfluous proteins and
      endotoxins. Here, we provide a comprehensive overview of a selection of key
      purification methodologies currently being applied in both academic and
      industrial settings and discuss how innovative and effective protocols such as
      aqueous two-phase partitioning, membrane chromatography, and high-performance
      tangential flow filtration may be applied independently of or in conjunction with
      more traditional protocols for downstream processing applications. 

PMID- 24455687
TI  - Oral Immunogenicity of plant-made Mycobacterium tuberculosis ESAT6 and CFP10.
AB  - Two lines of transgenic carrot plants producing Mycobacterium tuberculosis
      proteins (ESAT6 and CFP10) have been constructed. The target proteins are present
      in carrot storage roots at a level not less than 0.056% of the total storage
      protein (TSP) for ESAT6 and 0.002% of TSP for CFP10. As has been shown, oral
      immunization of mice induces both the cell-mediated and humoral immunities. These
      data suggest that the proteins in question are appropriate as a candidate edible
      vaccine against tuberculosis. 

PMID- 24455688
TI  - Profiling of hepatocellular carcinoma cell cycle regulating genes targeted by
      calycosin.
AB  - We cocultured calycosin with human hepatocellular carcinoma cell line (BEL-7402)
      to investigate the effect on cell proliferation. Calycosin can markedly block the
      cell growth in G1 phase (P < 0.01) on the IC50 concentration. There were
      seventeen genes involved in cell-cycle regulation showing differentially
      expressed in treated cells detected by gene chip. Eight genes were upregulated
      and nine genes were downregulated. Downregulated TFDP-1, CDKN2D, and SPK2 and
      upregulated CDC2 and CCNB1 might affect cell cycle of tumor cells. Furthermore,
      we checked the transcription pattern using 2D gel method to find different
      expression of proteins in human hepatocellular carcinoma cells after exposure to
      calycosin. Fourteen proteins were identified by matrix-assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Twelve
      proteins expression were increased such as transgelin 2, pyridoxine 5'-phosphate,
      stress-induced-phosphoprotein 1, peroxiredoxin 1, endoplasmic reticulum protein
      29, and phosphoglycerate mutase 1. Only thioredoxin peroxidase and high-mobility
      group box1 proteins' expression decreased. Both genes and proteins changes might
      be relate to the mechanism of antitumor effect under treatment of calycosin. In
      conclusion, calycosin has a potential effect to inhibit the BEL-7402 cell growth
      by inhibiting some oncogene expression and increasing anticancer genes
      expression, what is more, by blocking cell cycle. 

PMID- 24455689
TI  - Interplay between peptide bond geometrical parameters in nonglobular structural
      contexts.
AB  - Several investigations performed in the last two decades have unveiled that
      geometrical parameters of protein backbone show a remarkable variability.
      Although these studies have provided interesting insights into one of the basic
      aspects of protein structure, they have been conducted on globular and water
      soluble proteins. We report here a detailed analysis of backbone geometrical
      parameters in nonglobular proteins/peptides. We considered membrane proteins and
      two distinct fibrous systems (amyloid-forming and collagen-like peptides).
      Present data show that in these systems the local conformation plays a major role
      in dictating the amplitude of the bond angle N-C(alpha)-C and the propensity of
      the peptide bond to adopt planar/nonplanar states. Since the trends detected here
      are in line with the concept of the mutual influence of local geometry and
      conformation previously established for globular and water-soluble proteins, our
      analysis demonstrates that the interplay of backbone geometrical parameters is an
      intrinsic and general property of protein/peptide structures that is preserved
      also in nonglobular contexts. For amyloid-forming peptides significant
      distortions of the N-C(alpha)-C bond angle, indicative of sterical hidden strain,
      may occur in correspondence with side chain interdigitation. The correlation
      between the dihedral angles Deltaomega/psi in collagen-like models may have
      interesting implications for triple helix stability.

PMID- 24455690
TI  - Description of the vasospasm phenomena following perimesencephalic nonaneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-NASAH) is
      characterized by a benign course compared with aneurysmal SAH. While vasospasm
      (VS) after aneurysmal SAH is considered responsible for serious complications, VS
      post-PM-NASAH is not well documented. Our purpose was to characterize the
      incidence and course of VS among 63 patients--one of the largest databases of PM
      NASAH patients with documented blood flow velocities in the literature. METHODS:
      Data from 63 patients that were admitted with PM-NASAH from 2000 to 2012 and
      underwent transcranial Doppler tests to assess cranial vessel flow velocity was
      analyzed. RESULTS: On average, the maximal flow velocity was measured on the 7th
      day after hemorrhage. Higher risk for VS was associated with younger age, female
      sex, and higher Hunt and Hess scores, a lower risk for patients treated with
      statins (P < 0.05). Using velocity thresholds for diagnosis of VS, 49.2% showed
      evidence of VS. This is the first description of blood flow velocities in PM
      NASAH. VS average onset was on the 4th day, average cessation on day 15 after
      hemorrhage. No patients showed clinical manifestation of VS. CONCLUSIONS: VS post
      PM-NASAH is not as rare as previously believed. However, its lack of clinical
      significance raises questions regarding the need for diagnosis and may suggest a
      less intensive treatment protocol.

PMID- 24455691
TI  - Start-up characteristics of a granule-based anammox UASB reactor seeded with
      anaerobic granular sludge.
AB  - The granulation of anammox sludge plays an important role in the high nitrogen
      removal performance of the anammox reactor. In this study, anaerobic granular
      sludge was selected as the seeding sludge to start up anammox reactor in order to
      directly obtain anammox granules. Results showed that the anammox UASB reactor
      was successfully started up by inoculating anaerobic granular sludge, with
      substrate capacity of 4435.2 mg/(L . d) and average ammonium and nitrite removal
      efficiency of 90.36% and 93.29%, respectively. During the start-up course, the
      granular sludge initially disintegrated and then reaggregated and turned red,
      suggesting the high anammox performance. Zn-Fe precipitation was observed on the
      surface of granules during the operation by SEM-EDS, which would impose
      inhibition to the anammox activity of the granules. Accordingly, it is suggested
      to relatively reduce the trace metals concentrations, of Fe and Zn in the
      conventional medium. The findings of this study are expected to be used for a
      shorter start-up and more stable operation of anammox system.

PMID- 24455692
TI  - Introducing a method of in vitro testing of different anchoring systems used for
      female incontinence and prolapse surgery.
AB  - AIMS: To develop a method for in vitro testing to compare different
      intracorporeal anchoring systems (AS) used, for example, in single-incision
      slings or vaginal meshes. Intracorporeal fixation needs reliable anchorage
      systems, which keep the implant in the operative and early postoperative phase in
      place. Up to now, the impact of the design of current anchor systems and their
      capability to provide sufficient retention forces is not known. METHODS: Four AS
      ("PelFix", "Surelift", "TFS", and "MiniArc") were evaluated in an animal model
      and a ballistic gelatine model with pull-out tests. We performed ANOVA with post
      hoc Bonferroni. Results were presented as mean values whereby a significance
      level of <0.05 was considered significant. RESULTS: The four systems showed
      significantly different pull-out forces. Depending on mesh structure, size, and
      form of the AS, mechanical strain resulted in deformation with local peak
      stresses. Under the condition of form stability, relative differences of pull-out
      forces did not change in different tissues. CONCLUSIONS: Reliable testing of
      different AS in their ability to keep mesh implants in place can be done in
      animal models and in especially designed ballistic gelatine. These methods of
      testing will help to modify AS in novel pelvic floor implants.

PMID- 24455693
TI  - Association of iron depletion with menstruation and dietary intake indices in
      pubertal girls: the healthy growth study.
AB  - The aim of the present study was to investigate the associations of iron
      depletion (ID) with menstrual blood losses, lifestyle, and dietary habits, in
      pubertal girls. The study sample comprised 1222 girls aged 9-13 years old.
      Biochemical, anthropometrical, dietary, clinical, and physical activity data were
      collected. Out of 274 adolescent girls with menses, 33.5% were found to be iron
      depleted (defined as serum ferritin < 12 MUg/L) compared to 15.9% out of 948
      girls without menses. Iron-depleted girls without menses were found to have lower
      consumption of poultry (P = 0.017) and higher consumption of fruits (P = 0.044)
      and fast food (P = 0.041) compared to their peers having normal iron status.
      Multivariate logistic regression analysis showed that girls with menses were 2.57
      (95% CI: 1.37, 4.81) times more likely of being iron depleted compared to girls
      with no menses. Iron depletion was found to be associated with high calcium
      intake, high consumption of fast foods, and low consumption of poultry and
      fruits. Menses was the only factor that was found to significantly increase the
      likelihood of ID in these girls. More future research is probably needed in order
      to better understand the role of diet and menses in iron depletion.

PMID- 24455694
TI  - Effects of Tamarindus indica fruit pulp extract on abundance of HepG2 cell lysate
      proteins and their possible consequential impact on metabolism and inflammation.
AB  - The fruit pulp extract of Tamarindus indica has been reported for its antioxidant
      and hypolipidemic properties. In this study, the methanol extract of T. indica
      fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate
      proteins. Cell lysate was extracted from HepG2 cells grown in the absence and
      presence of the methanol extract of T. indica fruit pulp. Approximately 2500
      spots were resolved using two-dimensional gel electrophoresis and the abundance
      of 20 cellular proteins was found to be significantly reduced. Among the proteins
      of reduced abundance, fourteen, including six proteins involved in metabolism
      (including ethanolamine phosphate cytidylyltransferase), four mitochondrial
      proteins (including prohibitin and respiratory chain proteins), and four proteins
      involved in translation and splicing, were positively identified by mass
      spectrometry and database search. The identified HepG2 altered abundance
      proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA)
      software, are suggestive of the effects of T. indica fruit pulp extract on
      metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the
      methanol fruit pulp extract of T. indica was shown to cause reduced abundance of
      HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative
      phosphorylation, protein synthesis, and cellular metabolism. 

PMID- 24455695
TI  - Six-minute walking distance improvement after pulmonary rehabilitation is
      associated with baseline lung function in complex COPD patients: a retrospective
      study.
AB  - INTRODUCTION: Conflicting results have been so far reported about baseline lung
      function, as predicting factor of pulmonary rehabilitation (PR) efficacy. AIM: To
      ascertain whether or not baseline lung function could predict a benefit in terms
      of a significant change in 6-min walk test (6 MWT) after PR. METHODS: Seventy
      five stable moderate-to-severe COPD inpatients with comorbidities (complex COPD),
      allocated to a three-week PR program, were retrospectively evaluated. Pulmonary
      function, 6 MWT, dyspnea (BDI/TDI), and quality of life (EQ-VAS) were assessed
      before and after PR program. The patients were divided into two groups depending
      on the change in 6 MWT (responders > 30 m and nonresponders <= 30 m). Logistic
      regression analysis was used. Results. After PR, 6 MWT performance all outcome
      measures significantly improved (P < 0.01). Compared to nonresponders (N = 38),
      the responders (N = 37) had lower values in baseline lung function (P < 0.01).
      Logistic regression analysis showed that FEV1 < 50% pred and TL, CO < 50% pred
      were independent predictors of PR efficacy. CONCLUSIONS: Our study shows that in
      stable moderate-to-severe complex COPD inpatients, baseline lung function may
      predict the response to PR in terms of 6 MWT. We also found that complex COPD
      patients with poor lung function get more benefit from PR.

PMID- 24455697
TI  - Propionibacterium acnes in human health and disease.

PMID- 24455698
TI  - Cardiovascular autonomic neuropathy in context of other complications of type 2
      diabetes mellitus.
AB  - The aim of this study was to investigate the relationship between cardiac
      autonomic neuropathy (CAN) and other micro- and macrovascular complications and
      risk factors for type 2 diabetes. We included, in this study, 149 patients with
      type 2 diabetes. We evaluated their cardiovascular risk factors, demographic
      data, and any major micro- and macrovascular complications of their diabetes.
      Assessments of CAN were based upon Ewing's battery. RESULTS: CAN was present in
      38.9% of patients. In the CAN group, the duration of diabetes, BMI, systolic
      blood pressure, lipid levels, and HBA1c were all significantly higher than those
      in the other group. A significant association was found between CAN and
      retinopathy, peripheral neuropathy, ABI, and IMT. Multivariate logistic
      regression demonstrated that, in type 2 diabetes, the odds of CAN (OR (95%
      confidence intervals)) increase with the age of the patients (1.68 (1,4129
      2.0025)), the average diabetes duration (0.57 (0.47-0.67)), cholesterol (1.009
      (1.00-1.01)), HbA1c levels (1.88 (1.31-2.72)), peripheral neuropathy (15.47 (5.16
      46.38)), BMI (1.12 (1.05-1.21)), and smoking (2.21 (1.08-4.53)). CONCLUSIONS:
      This study shows that CAN in type 2 diabetes is significantly associated with
      other macro- and microvascular complications and that there are important
      modifiable risk factors for its development.

PMID- 24455699
TI  - Genotypically different clones of Staphylococcus aureus are diverse in the
      antimicrobial susceptibility patterns and biofilm formations.
AB  - This study evaluated whether genotypically different clinical isolates of S.
      aureus have similar susceptibilities to individual antibiotics. It further aims
      to check the impact of biofilm on the in vitro activity of vancomycin,
      daptomycin, linezolid, and tigecycline against S. aureus clones. The study used a
      total of 60 different clinical MSSA and MRSA isolates. Susceptibilities were
      performed in planktonic cultures by macrobroth dilution and epsilon-test (E test)
      system. Biofilm production was determined using an adherent plate assay. The
      efficacy of antimicrobial activities against biofilms formation was checked using
      confocal laser scanning microscopy (CLSM). The study found that similar and
      different spa, MLST, and SCCmec types displayed high variation in their
      susceptibilities to antibiotics with tigecycline and daptomycin being the most
      effective. The biofilms were found resistant to high concentrations of most
      antibiotics tested with daptomycin being the most effective drug used in adhesive
      biofilms. A considerable difference exists among similar and various clone types
      against antibiotics tested. This variation could have contributed to the degree
      of virulence even within the same clonal genotype and enhanced heterogeneity in
      the infection potential. Thus, the development of a rapid and precise
      identification profile for each clone in human infections is important. 

PMID- 24455696
TI  - Role of redox signaling in neuroinflammation and neurodegenerative diseases.
AB  - Reactive oxygen species (ROS), a redox signal, are produced by various enzymatic
      reactions and chemical processes, which are essential for many physiological
      functions and act as second messengers. However, accumulating evidence has
      implicated the pathogenesis of several human diseases including neurodegenerative
      disorders related to increased oxidative stress. Under pathological conditions,
      increasing ROS production can regulate the expression of diverse inflammatory
      mediators during brain injury. Elevated levels of several proinflammatory factors
      including cytokines, peptides, pathogenic structures, and peroxidants in the
      central nervous system (CNS) have been detected in patients with
      neurodegenerative diseases such as Alzheimer's disease (AD). These
      proinflammatory factors act as potent stimuli in brain inflammation through
      upregulation of diverse inflammatory genes, including matrix metalloproteinases
      (MMPs), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and
      adhesion molecules. To date, the intracellular signaling mechanisms underlying
      the expression of target proteins regulated by these factors are elusive. In this
      review, we discuss the mechanisms underlying the intracellular signaling
      pathways, especially ROS, involved in the expression of several inflammatory
      proteins induced by proinflammatory factors in brain resident cells.
      Understanding redox signaling transduction mechanisms involved in the expression
      of target proteins and genes may provide useful therapeutic strategies for brain
      injury, inflammation, and neurodegenerative diseases. 

PMID- 24455700
TI  - Identification of age-related macular degeneration related genes by applying
      shortest path algorithm in protein-protein interaction network.
AB  - This study attempted to find novel age-related macular degeneration (AMD) related
      genes based on 36 known AMD genes. The well-known shortest path algorithm,
      Dijkstra's algorithm, was applied to find the shortest path connecting each pair
      of known AMD related genes in protein-protein interaction (PPI) network. The
      genes occurring in any shortest path were considered as candidate AMD related
      genes. As a result, 125 novel AMD genes were predicted. The further analysis
      based on betweenness and permutation test indicates that there are 10 genes
      involved in the formation or development of AMD and may be the actual AMD related
      genes with high probability. We hope that this contribution would promote the
      study of age-related macular degeneration and discovery of novel effective
      treatments. 

PMID- 24455701
TI  - Modes of inhibition of alpha -amylase and alpha -glucosidase by aqueous extract
      of Morinda lucida Benth leaf.
AB  - Diabetes mellitus is a metabolic disorder of glucose metabolism. The management
      of blood glucose level is the hallmark in the treatment of this disease. This may
      be achieved through the use of oral hypoglycemic drugs such as biguanides,
      insulin secretagogues, and alpha-glucosidase inhibitors. The purpose of the
      present study was to investigate the inhibitory effect of Morinda lucida leaf
      extracts on the activities of alpha-amylase and alpha-glucosidase. This was
      performed using alpha-amylase from Aspergillus oryzae and alpha-glucosidase from
      Saccharomyces cerevisiae. Aqueous extract of Morinda lucida gave the highest
      percentage yield (9.99%) of the plant out of the three extracts (compared to
      acetone and ethanolic extracts) and possesses the highest inhibitory activity
      against alpha-amylase (IC50 value of 2.30 mg/mL) and alpha-glucosidase (IC50
      value of 2.00 mg/mL). Kinetic analysis revealed that the aqueous extract of this
      plant leaf inhibited the alpha-amylase competitively but displayed mixed
      noncompetitive mode of inhibition towards alpha-glucosidase. It can be concluded
      that aqueous extract of Morinda lucida exhibited the best inhibitory activity on
      the two enzymes studied and the presence of phytochemicals like flavonoids,
      saponins, and tannins may have contributed greatly to the inhibitory activity of
      the plant extract.

PMID- 24455702
TI  - An uncommon plant growth regulator, diethyl aminoethyl hexanoate, is highly
      effective in tissue cultures of the important medicinal plant purple coneflower
      (Echinacea purpurea L.).
AB  - We investigated the effects of various concentrations of diethyl aminoethyl
      hexanoate (DA-6) on the regeneration and growth of adventitious buds in in vitro
      purple coneflower cultures. Among the 3 types of explants tested, leaf explants
      required higher concentrations of DA-6 than petiole and root explants in order to
      obtain high regeneration rates, while root explants required the lowest
      concentration of DA-6. Additionally, explants with higher ploidy levels were more
      sensitive to the addition of DA-6, while explants with lower ploidy levels
      required higher concentrations of DA-6 to achieve its maximal regeneration rate.
      Interestingly, the application of a concentration that was conducive to the
      regeneration of explants with lower ploidy levels was inhibitory to the
      regeneration of explants with higher ploidy levels. Moreover, during the growth
      of regenerated buds, DA-6 application significantly improved plant height and
      weight, root weight, root thickness, root number, primary root length, total root
      length, and root/top ratio. Differences in the responses of explants to
      supplementation with DA-6 were also observed among explants with different ploidy
      levels, with buds having lower ploidy levels responding to lower concentrations
      of DA-6. Taken together, the results of the present experiments showed that
      proper application of DA-6 could increase in vitro culture efficiency in purple
      coneflower. 

PMID- 24455703
TI  - Grateloupia tenuis Wang et Luan sp. nov. (Halymeniaceae, Rhodophyta): a new
      species from South China Sea based on morphological observation and rbcL gene
      sequences analysis.
AB  - Grateloupia tenuis Wang et Luan sp. nov. is a new species described from
      Lingshui, Hainan Province, South China Sea. Based on the external form and
      internal structure, combined with rbcL gene sequence analysis, Grateloupia tenuis
      is distinct from other Grateloupia species as follows: (1) thalli is slippery and
      cartilaginous in texture; possess fewer branches, relatively slight main axes,
      and two or three dichotomous branches; (2) cortex is 5-6 layers; medulla is solid
      when young, but hollow in old branches; reproductive structures are dispersed in
      main axes of thalli and lower portions of branchlets; exhibits Grateloupia-type
      auxiliary cell ampullae; (3) the four studied G. tenuis sequences were positioned
      in a large Grateloupia clade of Halymeniaceae, which included sister group
      generitype G. filicina with 68 bp differences; G. tenuis was determined to be a
      sister taxon to the G. catenata, G. ramosissima, G. orientalis, and G. filiformis
      subclade. The pairwise distances between G. tenuis and these species were 39 to
      50 bp. The sequences of G. tenuis differed by 81-108 bp from the sequences of
      other samples in Grateloupia; there are 114-133 bp changes between G. tenuis and
      other genera of Halymeniaceae. In final analysis, we considered Grateloupia
      tenuis Wang et Luan sp. nov. to be a new species of genus Grateloupia.

PMID- 24455704
TI  - Outcome of prolonged ventricular fibrillation and CPR in a rat model of chronic
      ischemic left ventricular dysfunction.
AB  - Patients with chronic left ventricular (LV) dysfunction are assumed to have a
      lower chance of successful CPR and lower likelihood of ultimate survival.
      However, these assumptions have rarely been documented. Therefore, we
      investigated the outcome of prolonged ventricular fibrillation (VF) and CPR in a
      rat model of chronic LV dysfunction. Sprague-Dawley rats were randomized to (1)
      chronic LV dysfunction: animals underwent left coronary artery ligation; and (2)
      sham control. Echocardiography was used to measure cardiac performance before
      surgery and 4 weeks after surgery. Four weeks after surgical intervention, 8 min
      of VF was induced and defibrillation was delivered after 8 min of CPR. LV
      dilation and low ejection fraction were observed 4 weeks after coronary ligation.
      With optimal chest compressions, coronary perfusion pressure values during CPR
      were well maintained and indistinguishable between groups. There were no
      differences in resuscitability and numbers of shock required for successful
      resuscitation between groups. Despite the significantly decreased cardiac index
      in LV dysfunction animals before induction of VF, no differences in cardiac index
      were observed between groups following resuscitation, which was associated with
      the insignificant difference in postresuscitation survival. In conclusion, the
      outcomes of CPR were not compromised by the preexisting chronic LV dysfunction.

PMID- 24455706
TI  - Heavy water reduces GFP expression in prokaryotic cell-free assays at the
      translation level while stimulating its transcription.
AB  - The in vitro proliferation of prokaryotic and eukaryotic cells is remarkably
      hampered in the presence of heavy water (D2O). Impairment of gene expression at
      the transcription or translation level can be the base for this effect. However,
      insights into the underlying mechanisms are lacking. Here, we employ a cell-free
      expression system for the quantitative analysis of the effect of increasing
      percentages of D2O on the kinetics of in-vitro GFP expression. Experiments are
      designed to discriminate the rates of transcription, translation, and protein
      folding using pDNA and mRNA vectors, respectively. We find that D2O significantly
      stimulates GFP expression at the transcription level but acts as a suppressor at
      translation and maturation (folding) in a linear dose-dependent manner. At a D2O
      concentration of 60%, the GFP expression rate was reduced to 40% of an
      undisturbed sample. We observed a similar inhibition of GFP expression by D2O in
      a recombinant Escherichia coli strain, although the inhibitory effect is less
      pronounced. These results demonstrate the suitability of cell-free systems for
      quantifying the impact of heavy water on gene expression and establish a platform
      to further assess the potential therapeutic use of heavy water as
      antiproliferative agent. 

PMID- 24455705
TI  - Biomarkers in Japanese encephalitis: a review.
AB  - JE is a flavivirus generated dreadful CNS disease which causes high mortality in
      various pediatric groups. JE disease is currently diagnosed by measuring the
      level of viral antigens and virus neutralization IgM antibodies in blood serum
      and CSF by ELISA. However, it is not possible to measure various disease
      identifying molecules, structural and molecular changes occurred in tissues, and
      cells by using such routine methods. However, few important biomarkers such as
      cerebrospinal fluid, plasma, neuro-imaging, brain mapping, immunotyping,
      expression of nonstructural viral proteins, systematic mRNA profiling, DNA and
      protein microarrays, active caspase-3 activity, reactive oxygen species and
      reactive nitrogen species, levels of stress-associated signaling molecules, and
      proinflammatory cytokines could be used to confirm the disease at an earlier
      stage. These biomarkers may also help to diagnose mutant based environment
      specific alterations in JEV genotypes causing high pathogenesis and have immense
      future applications in diagnostics. There is an utmost need for the development
      of new more authentic, appropriate, and reliable physiological, immunological,
      biochemical, biophysical, molecular, and therapeutic biomarkers to confirm the
      disease well in time to start the clinical aid to the patients. Hence, the
      present review aims to discuss new emerging biomarkers that could facilitate more
      authentic and fast diagnosis of JE disease and its related disorders in the
      future. 

PMID- 24455707
TI  - Contrast enhanced ultrasound of the kidneys: what is it capable of?
AB  - One of the many imaging uses of contrast enhanced ultrasound (CEUS) is studying a
      wide variety of kidney pathology, due to its ability to detect microvascular
      blood flow in real time without affecting renal function. CEUS enables dynamic
      assessment and quantification of microvascularisation up to capillary perfusion.
      The objective of this paper is to briefly refresh basic knowledge of ultrasound
      (US) contrast agents' physical properties, to study technical details of CEUS
      scanning in the kidneys, and to review the commonest renal indications for CEUS,
      with imaging examples in comparison to baseline unenhanced US and computed
      tomography when performed. Safety matters and limitations of CEUS of the kidneys
      are also discussed. 

PMID- 24455709
TI  - Human arthropod-borne viral infections.

PMID- 24455708
TI  - Do telomeres adapt to physiological stress? Exploring the effect of exercise on
      telomere length and telomere-related proteins.
AB  - Aging is associated with a tissue degeneration phenotype marked by a loss of
      tissue regenerative capacity. Regenerative capacity is dictated by environmental
      and genetic factors that govern the balance between damage and repair. The age
      associated changes in the ability of tissues to replace lost or damaged cells is
      partly the cause of many age-related diseases such as Alzheimer's disease,
      cardiovascular disease, type II diabetes, and sarcopenia. A well-established
      marker of the aging process is the length of the protective cap at the ends of
      chromosomes, called telomeres. Telomeres shorten with each cell division and with
      increasing chronological age and short telomeres have been associated with a
      range of age-related diseases. Several studies have shown that chronic exposure
      to exercise (i.e., exercise training) is associated with telomere length
      maintenance; however, recent evidence points out several controversial issues
      concerning tissue-specific telomere length responses. The goals of the review are
      to familiarize the reader with the current telomere dogma, review the literature
      exploring the interactions of exercise with telomere phenotypes, discuss the
      mechanistic research relating telomere dynamics to exercise stimuli, and finally
      propose future directions for work related to telomeres and physiological stress.

PMID- 24455711
TI  - Highlights from the functional single nucleotide polymorphisms associated with
      human muscle size and strength or FAMuSS study.
AB  - The purpose of the Functional Single Nucleotide Polymorphisms Associated with
      Human Muscle Size and Strength study or FAMuSS was to identify genetic factors
      that dictated the response of health-related fitness phenotypes to resistance
      exercise training (RT). The phenotypes examined were baseline muscle strength and
      muscle, fat, and bone volume and their response to RT. FAMuSS participants were
      1300 young (24 years), healthy men (42%) and women (58%) that were primarily of
      European-American descent. They were genotyped for ~500 polymorphisms and
      completed the Paffenbarger Physical Activity Questionnaire to assess energy
      expenditure and time spent in light, moderate, and vigorous intensity habitual
      physical activity and sitting. Subjects then performed a 12-week progressive,
      unilateral RT program of the nondominant arm with the dominant arm used as a
      comparison. Before and after RT, muscle strength was measured with the maximum
      voluntary contraction and one repetition maximum, while MRI measured muscle, fat,
      and bone volume. We will discuss the history of how FAMuSS originated, provide a
      brief overview of the FAMuSS methods, and summarize our major findings regarding
      genotype associations with muscle strength and size, body composition,
      cardiometabolic biomarkers, and physical activity. 

PMID- 24455710
TI  - Obesity, insulin resistance, and metabolic syndrome: a study in WNIN/Ob rats from
      a pancreatic perspective.
AB  - Alterations in pancreatic milieu to adapt to physiological shifts occurring in
      conditions of obesity and metabolic syndrome (MS) have been documented, though
      mechanisms leading to such a state have remained elusive so far. The data
      presented here tries to look at the gravity of metabolic insult during the early
      and prolonged phases of obesity/insulin resistance (IR) depicted in WNIN/Ob
      strain of rats-an obese euglycemic mutant rat model developed indigenously at our
      institute which is highly vulnerable for a variety of degenerative diseases. The
      present results in situ show the participation of several confounding factors in
      the pancreatic milieu that collectively coprecipitates for a state of profound
      inflammation in the pancreas (among Mutant compared to Lean/Control) which gets
      worsened with age. These include hypertrophy, macrophage infiltration
      (CD11b/TNFalpha/IL6), apoptosis, beta-cell vacuolation, hyperinsulinemia (HI),
      and stress markers (RL-77/HSP104/TBARS) all of which correlated well with indices
      for obesity (2-3 fold), IR (1.5-3 fold), and HI (2-3 fold). Further, supportive
      data was also obtained from in vitro studies using islet cell cultures amongst
      phenotypes. Taken together, these results advocate that inflammation was the
      major precipitating factor to cause islet cell dysfunctions (in situ and in
      vitro) in these Mutant rats compared to their Lean littermates and parental
      Control. 

PMID- 24455712
TI  - Impact of mean platelet volume on combined safety endpoint and vascular and
      bleeding complications following percutaneous transfemoral transcatheter aortic
      valve implantation.
AB  - BACKGROUND: Vascular and bleeding complications remain important complications in
      patients undergoing percutaneous transfemoral transcatheter aortic valve
      implantation (TF-TAVI). Platelets play an important role in bleeding events. Mean
      platelet volume (MPV) is an indicator of platelet activation. The objective of
      this study was to assess whether low MPV is an indicator of major vascular and
      bleeding complications following TF-TAVI. METHODS: A retrospective cohort study
      of 330 subjects undergoing TF-TAVI implantation was performed. The primary study
      endpoint was the occurrence of combined safety endpoint (CSEP); secondary
      endpoints included major vascular complications and life-threatening bleeding.
      Endpoints were defined according to Valve Academic Research Consortium 2.
      RESULTS: The CSEP at 30 days was reached in 30.9%; major vascular complications
      were observed in 14.9% while life-threatening bleeding occurred in 20.6%.
      Logistic Euroscore and MPV were independent predictors of CSEP. Predictors of
      vascular complications were female sex, previous myocardial infarction, red blood
      cell distribution width (RDW), and MPV while predictors of life-threatening
      bleeding were peripheral arterial disease, RDW, and MPV. CONCLUSION: A low
      baseline MPV was shown for the first time to be a significant predictor of CSEP,
      major vascular complications, and life-threatening bleeding following TF-TAVI.

PMID- 24455713
TI  - Antimicrobial activity, growth inhibition of human tumour cell lines, and
      phytochemical characterization of the hydromethanolic extract obtained from
      Sapindus saponaria L. aerial parts.
AB  - The hydromethanolic extract of Sapindus saponaria L. aerial parts was
      investigated for antimicrobial activity (against several Gram-positive and Gram
      negative bacteria and fungi) and capacity to inhibit the growth of different
      human tumor cell lines as also nontumor liver cells. The evaluated extract was
      further characterized in terms of phytochemicals using UV, (1)H-NMR, (13)C-NMR,
      and MS spectroscopic tools. The extract has shown a significant antimicrobial
      activity on all tested bacterial and fungal species. The best activity was
      achieved against Bacillus cereus and Staphylococcus aureus among bacteria and
      against all three Penicillium species tested. It also revealed cytotoxicity
      against human colon (HCT-15), cervical (HeLa), breast (MCF-7), and lung (NCI
      H460) carcinoma cell lines, with HeLa being the most susceptible tumor cell line.
      The extract was not toxic for nontumor liver cells. Chromatographic separation of
      the extract resulted in the isolation and identification of stigmasterol,
      oleanolic acid, luteolin, luteolin 8-C-beta-glucoside (orientin), luteolin 6-C
      beta-glucoside (isoorientin), luteolin 7-O-beta-glucuronide, and rutin. The
      results of the present findings may be useful for the discovery of novel
      antitumor and antimicrobial agents from plant origin. 

PMID- 24455714
TI  - Prediction of substrate-enzyme-product interaction based on molecular descriptors
      and physicochemical properties.
AB  - It is important to correctly and efficiently predict the interaction of substrate
      enzyme and to predict their product in metabolic pathway. In this work, a novel
      approach was introduced to encode substrate/product and enzyme molecules with
      molecular descriptors and physicochemical properties, respectively. Based on this
      encoding method, KNN was adopted to build the substrate-enzyme-product
      interaction network. After selecting the optimal features that are able to
      represent the main factors of substrate-enzyme-product interaction in our
      prediction, totally 160 features out of 290 features were attained which can be
      clustered into ten categories: elemental analysis, geometry, chemistry, amino
      acid composition, predicted secondary structure, hydrophobicity, polarizability,
      solvent accessibility, normalized van der Waals volume, and polarity. As a
      result, our predicting model achieved an MCC of 0.423 and an overall prediction
      accuracy of 89.1% for 10-fold cross-validation test. 

PMID- 24455716
TI  - N-acetylcysteine prevents hypertension via regulation of the ADMA-DDAH pathway in
      young spontaneously hypertensive rats.
AB  - Asymmetric dimethylarginine (ADMA) reduces nitric oxide (NO), thus causing
      hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase
      (DDAH), which can be inhibited by oxidative stress. N-Acetylcysteine (NAC), an
      antioxidant, can facilitate glutathione (GSH) synthesis. We aimed to determine
      whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in
      spontaneously hypertensive rats (SHR). Rats aged 4 weeks were assigned into 3
      groups (n = 8/group): control Wistar Kyoto rats (WKY), SHR, and SHR receiving 2%
      NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had
      higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had
      elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower
      renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal
      superoxide production was higher in SHR than in WKY, whereas NAC therapy
      prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH
      ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The
      observed antihypertensive effects of NAC in young SHR might be due to restoration
      of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our
      findings highlight the impact of NAC on the development of hypertension by
      regulating ADMA-DDAH pathway. 

PMID- 24455717
TI  - Autoclaved tumor bone for skeletal reconstruction in paediatric patients: a low
      cost alternative in developing countries.
AB  - We reviewed in this series forty patients of pediatric age who underwent
      resection for malignant tumors of musculoskeletal system followed by biological
      reconstruction. Our surgical procedure for reconstruction included (1) wide en
      bloc resection of the tumor; (2) curettage of tumor from the resected bone; (3)
      autoclaving for 8 minutes (4) bone grafting from the fibula (both vascularized
      and nonvascularized fibular grafts used); (5) reimplantation of the autoclaved
      bone into the host bone defect and fixation with plates. Functional evaluation
      was done using MSTS scoring system. At final followup of at least 18 months (mean
      29.2 months), 31 patients had recovered without any complications. Thirty-eight
      patients successfully achieved a solid bony union between the graft and recipient
      bone. Three patients had surgical site infection. They were managed with wound
      debridement and flap coverage of the defect. Local recurrence and nonunion
      occurred in two patients each. One patient underwent disarticulation at hip due
      to extensive local disease and one died of metastasis. For patients with non
      union, revision procedure with bone graft and compression plates was successfully
      used. The use of autoclaved tumor grafts provides a limb salvage option that is
      inexpensive and independent of external resources and is a viable option for
      musculoskeletal tumor management in developing countries. 

PMID- 24455715
TI  - Patent ductus arteriosus in preterm infants: do we have the right answers?
AB  - Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants.
      Preterm newborns with PDA are at greater risk for several morbidities, including
      higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital
      organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical
      interventions for ligation of PDA are widely used. However, these interventions
      were reported to be associated with side effects. In the absence of clear
      restricted rules for application of these interventions, different strategies are
      adopted by neonatologists. Three different approaches have been investigated
      including prophylactic treatment shortly after birth irrespective of the state of
      PDA, presymptomatic treatment using echocardiography at variable postnatal ages
      to select infants for treatment prior to the duct becoming clinically
      significant, and symptomatic treatment once PDA becomes clinically apparent or
      hemodynamically significant. Future appropriately designed randomized controlled
      trials (RCTs) to refine selection of patients for medical and surgical treatments
      should be conducted. Waiting for new evidence, it seems wise to employ available
      clinical and echocardiographic parameters of a hemodynamically significant (HS)
      PDA to select patients who are candidates for medical treatment. Surgical
      ligation of PDA could be used as a back-up tool for those patients who failed
      medical treatment and continued to have hemodynamic compromise. 

PMID- 24455718
TI  - alphaV beta5 and CD44 are oxygen-regulated human embryonic stem cell attachment
      factors.
AB  - Human embryonic stem cells (hESCs) have great potential for clinical therapeutic
      use. However, relatively little is known of the mechanisms which dictate their
      specificity of adhesion to substrates through adhesion proteins including
      integrins. Previous observations demonstrated enhanced clonogenicity in reduced
      oxygen culture systems. Here, we demonstrated via antibody blocking experiments
      that alphaV beta5 and alpha 6 significantly promoted hESC attachment in 2% O2
      only, whereas blockage of CD44 inhibited cell attachment in 21% O2 alone.
      Immunofluorescence confirmed expression of alphaV beta5 and CD44 in both 2% O2
      and 21% O2 cultured hESCs while flow cytometry revealed significantly higher
      alphaV beta5 expression in 2% O2 versus 21% O2 cultured hESCs and higher CD44
      expression in 21% O2 versus 2% O2 cultured hESCs. Adhered hESCs following
      blockage of alphaV beta5 in 2% O2 displayed a reduction in nuclear colocalisation
      of Oct-4 and Nanog with little effect observed in 21% O2. Blockage of CD44 had
      the converse effect with dramatic reductions in nuclear colocalisation of Oct-4
      and Nanog in 21% O2 cultured hESC which retained adherence, but not in 2% O2
      cultured cells. Identification of oxygen-dependent substrate attachment
      mechanisms in hESCs has the potential to play a role in the development of novel
      substrates to improve hESC attachment and culture.

PMID- 24455719
TI  - Coronary CT angiography in coronary artery disease: correlation between virtual
      intravascular endoscopic appearances and left bifurcation angulation and coronary
      plaques.
AB  - The aim of this study is to investigate the relationship between intraluminal
      appearances of coronary plaques and left coronary bifurcation angle and plaque
      components using coronary CT virtual intravascular endoscopy (VIE). Fifty
      patients suspected of coronary artery disease undergoing coronary CT angiography
      were included in the study. The left bifurcation angle in patients with diseased
      left coronary artery which was measured as 94.3 degrees  +/- 16.5 is
      significantly larger than that in patients with normal left coronary artery,
      which was measured as 76.5 degrees  +/- 15.9 (P < 0.001). Irregular VIE
      appearances were found in 10 out of 11 patients with mixed plaques in the left
      anterior descending (LAD) and left circumflex (LCx), while, in 29 patients with
      calcified plaques in the LAD and LCx, irregular VIE appearances were only noticed
      in 5 patients. Using 80 degrees  as a cut-off value to determine coronary artery
      disease, smooth VIE appearances were found in 95% of patients (18/19) with left
      bifurcation angle of less than 80 degrees , while irregular VIE appearances were
      observed in nearly 50% of patients (15/31) with left bifurcation angle of more
      than 80 degrees . This preliminary study shows that VIE appearances of the
      coronary lumen are directly related to the types of plaques. 

PMID- 24455720
TI  - Walking on a tissue-specific disease-protein-complex heterogeneous network for
      the discovery of disease-related protein complexes.
AB  - Besides the pinpointing of individual disease-related genes, associating protein
      complexes to human inherited diseases is also of great importance, because a
      biological function usually arises from the cooperative behaviour of multiple
      proteins in a protein complex. Moreover, knowledge about disease-related protein
      complexes could also enhance the inference of disease genes and pathogenic
      genetic variants. Here, we have designed a computational systems biology approach
      to systematically analyse potential relationships between diseases and protein
      complexes. First, we construct a heterogeneous network which is composed of a
      disease-disease similarity layer, a tissue-specific protein-protein interaction
      layer, and a protein complex membership layer. Then, we propose a random walk
      model on this disease-protein-complex network for identifying protein complexes
      that are related to a query disease. With a series of leave-one-out cross
      validation experiments, we show that our method not only possesses high
      performance but also demonstrates robustness regarding the parameters and the
      network structure. We further predict a landscape of associations between human
      diseases and protein complexes. This landscape can be used to facilitate the
      inference of disease genes, thereby benefiting studies on pathology of diseases. 

PMID- 24455721
TI  - Moving toward personalized medicine in the methadone maintenance treatment
      program: a pilot study on the evaluation of treatment responses in Taiwan.
AB  - This pilot study simultaneously evaluated the effects of various factors,
      including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic
      characteristics, disease states, methadone-drug interactions (MDIs), and poly
      substance use, on the treatment responses among non-HIV patients in the methadone
      maintenance treatment program (MMTP) in Taiwan. A total of 178 patients were
      recruited from two major hospitals that provided MMTP services in southern
      Taiwan, and information regarding concomitant medications and diseases was
      acquired from the National Health Insurance (NHI) program. The results
      demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1
      2677T allele have positive effects on the methadone plasma concentration. In
      contrast, patients with HCV coinfection, alcohol problems, and psychiatric
      diseases may have a negative response to treatment. Thus, a comprehensive
      evaluation of treatment responses in the MMTP should include not only genetic
      polymorphisms in methadone metabolism and transporter proteins, but also
      concomitant diseases, MDIs, and poly-substance use. The results also suggest that
      personalized medicine may be indispensable for a better outcome of the MMTP. 

PMID- 24455722
TI  - Optimization of polygalacturonase production from a newly isolated Thalassospira
      frigidphilosprofundus to use in pectin hydrolysis: statistical approach.
AB  - The present study deals with the production of cold active polygalacturonase
      (PGase) by submerged fermentation using Thalassospira frigidphilosprofundus, a
      novel species isolated from deep waters of Bay of Bengal. Nonlinear models were
      applied to optimize the medium components for enhanced production of PGase.
      Taguchi orthogonal array design was adopted to evaluate the factors influencing
      the yield of PGase, followed by the central composite design (CCD) of response
      surface methodology (RSM) to identify the optimum concentrations of the key
      factors responsible for PGase production. Data obtained from the above mentioned
      statistical experimental design was used for final optimization study by linking
      the artificial neural network and genetic algorithm (ANN-GA). Using ANN-GA hybrid
      model, the maximum PGase activity (32.54 U/mL) was achieved at the optimized
      concentrations of medium components. In a comparison between the optimal output
      of RSM and ANN-GA hybrid, the latter favored the production of PGase. In
      addition, the study also focused on the determination of factors responsible for
      pectin hydrolysis by crude pectinase extracted from T. frigidphilosprofundus
      through the central composite design. Results indicated 80% degradation of pectin
      in banana fiber at 20  degrees C in 120 min, suggesting the scope of cold active
      PGase usage in the treatment of raw banana fibers.

PMID- 24455723
TI  - Plasma miR-126 is a potential biomarker for early prediction of type 2 diabetes
      mellitus in susceptible individuals.
AB  - Type 2 diabetes mellitus (T2DM) is a major public health problem in China.
      Diagnostic markers are urgently needed to identify individuals at risk of
      developing T2DM and encourage them to adapt to a healthier life style.
      Circulating miRNAs present important sources of noninvasive biomarkers of various
      diseases. Recently, a novel plasma microRNA signature was identified in T2DM.
      Here, we evaluated the T2DM-related miRNA signature in plasma of three study
      groups: normal (fasting glucose (FG), 4.8-5.2 mmol/L), T2DM-susceptible (FG, 6.1
      6.9 mmol/L), and T2DM individuals (FG, >= 7.0 mmol/L) and tested the feasibility
      of using circulating miRNAs to identify individuals at risk of developing T2DM.
      Among the 5 miRNAs included in the signature, miR-29b and miR-28-3p are not
      detectable. miR-15a and miR-223 have comparable expression levels among three
      groups. Notably, miR-126 is the only miRNA that showed significantly reduced
      expression in susceptible individuals and T2DM patients compared to normal
      individuals, suggesting that miR-126 in circulation may serve as a potential
      biomarker for early identification of susceptible individuals to T2DM.

PMID- 24455724
TI  - Immunohistochemical patterns in the interfollicular Caucasian scalps: influences
      of age, gender, and alopecia.
AB  - Skin ageing and gender influences on the scalp have been seldom studied. We
      revisited the changes in the interfollicular scalp. The study was performed on a
      population of 650 volunteers (300 women and 350 men) for over 7 years. Three age
      groups were selected in both genders, namely, subjects aged 20-35, 50-60, and 60
      70 years. The hair status was further considered according to nonalopecic and
      alopecic patterns and severity (discrete, moderate, and severe). Biopsies from
      the parietal area were processed for immunohistochemistry. Stromal cells were
      distinguished according to the presence of vimentin, Factor XIIIa, CD117, and
      versican. Blood and lymphatic vessels were highlighted by Ulex europaeus
      agglutinin-1 and human podoplanin immunoreactivities, respectively. Actinic
      elastosis was identified by the lysozyme coating of elastic fibres. The epidermis
      was explored using the CD44 variant 3 and Ki67 immunolabellings. Biplot analyses
      were performed. Immunohistochemistry revealed a prominent gender effect in young
      adults. Both Factor XIIIa+ dermal dendrocytes and the microvasculature size
      decreased with scalp ageing. Alopecia changes mimicked stress-induced premature
      senescence. 

PMID- 24455725
TI  - Antiatherosclerotic potential of clopidogrel: antioxidant and anti-inflammatory
      approaches.
AB  - BACKGROUND: Atherosclerosis is characterized by endothelial dysfunction, vascular
      inflammation, and the buildup of lipids, cholesterol, calcium, and cellular
      debris within the intima of the walls of large and medium size arteries.
      OBJECTIVE: To evaluate the effect of clopidogrel on atherosclerosis progression.
      MATERIALS AND METHODS: A total of 28 local domestic rabbits were assigned to four
      groups: normal control, atherogenic control, vehicle control, and clopidogrel
      treated. Serum triglycerides, total cholesterol, HDL-C, plasma high sensitive C
      reactive protein (hsCRP), plasma malondialdehyde (MDA), and plasma reduced
      glutathione (GSH) were measured at the end of the experiment. Immunohistochemical
      of aortic atherosclerotic changes were also performed. RESULTS: There was no
      statistically significant difference between atherogenic control group and
      vehicle group. Levels of lipid profile, atherogenic index, hsCRP, and MDA are
      increased while GSH levels were decreased in animals on atherogenic diet.
      Immunohistochemical analysis showed that aortic expressions of VCAM-1, MCP-1, TNF
      alpha , and IL-17A were significantly increased in atherogenic control group.
      Histopathologic finding showed that animals on atherogenic diet have significant
      atherosclerotic lesion. Compared to atherogenic control group clopidogrel do not
      have significant effect on lipid profile. Clopidogrel significantly reduces hsCRP
      and MDA levels and increases GSH level. Furthermore, clopidogrel treatment
      significantly reduced aortic expressions parameters and the histopathologic
      examination of the aortic arch showed a significant reduction of atherosclerotic
      lesion. CONCLUSIONS: This study outlines how clopidogrel reduces lipid
      peroxidation, systemic inflammation, and aortic expression of inflammatory
      markers and hence reduces the progression of atherosclerosis.

PMID- 24455726
TI  - Resistance training for diabetes prevention and therapy: experimental findings
      and molecular mechanisms.
AB  - Type 2 diabetes mellitus (T2D) is characterized by insulin resistance, impaired
      glycogen synthesis, lipid accumulation, and impaired mitochondrial function.
      Exercise training has received increasing recognition as a cornerstone in the
      prevention and treatment of T2D. Emerging research suggests that resistance
      training (RT) has the power to combat metabolic dysfunction in patients with T2D
      and seems to be an effective measure to improve overall metabolic health and
      reduce metabolic risk factors in diabetic patients. However, there is limited
      mechanistic insight into how these adaptations occur. This review provides an
      overview of the intervention data on the impact of RT on glucose metabolism. In
      addition, the molecular mechanisms that lead to adaptation in skeletal muscle in
      response to RT and that are associated with possible beneficial metabolic
      responses are discussed. Some of the beneficial adaptations exerted by RT include
      increased GLUT4 translocation in skeletal muscle, increased insulin sensitivity
      and hence restored metabolic flexibility. Increased energy expenditure and excess
      postexercise oxygen consumption in response to RT may be other beneficial
      effects. RT is increasingly establishing itself as an effective measure to
      improve overall metabolic health and reduce metabolic risk factors in diabetic
      patients. 

PMID- 24455727
TI  - Improving therapeutic ratio in head and neck cancer with adjuvant and cisplatin
      based treatments.
AB  - Advanced head and neck cancers are difficult to manage despite the large
      treatment arsenal currently available. The multidisciplinary effort to increase
      disease-free survival and diminish normal tissue toxicity was rewarded with
      better locoregional control and sometimes fewer side effects. Nevertheless,
      locoregional recurrence is still one of the main reasons for treatment failure.
      Today, the standard of care in head and neck cancer management is represented by
      altered fractionation radiotherapy combined with platinum-based chemotherapy.
      Targeted therapies as well as chronotherapy were trialled with more or less
      success. The aim of the current work is to review the available techniques, which
      could contribute towards a higher therapeutic ratio in the treatment of advanced
      head and neck cancer patients. 

PMID- 24455728
TI  - Why control activity? Evolutionary selection pressures affecting the development
      of physical activity genetic and biological regulation.
AB  - The literature strongly suggests that daily physical activity is genetically and
      biologically regulated. Potential identities of the responsible mechanisms are
      unclear, but little has been written concerning the possible evolutionary
      selection pressures leading to the development of genetic/biological controls of
      physical activity. Given the weak relationship between exercise endurance and
      activity levels and the differential genomic locations associated with the
      regulation of endurance and activity, it is probable that regulation of endurance
      and activity evolved separately. This hypothesis paper considers energy
      expenditures and duration of activity in hunter/gatherers, pretechnology farmers,
      and modern Western societies and considers the potential of each to selectively
      influence the development of activity regulation. Food availability is also
      considered given the known linkage of caloric restriction on physical activity as
      well as early data relating food oversupply to physical inactivity. Elucidating
      the selection pressures responsible for the genetic/biological control of
      activity will allow further consideration of these pressures on activity in
      today's society, especially the linkages between food and activity. Further,
      current food abundance is removing the cues for activity that were present for
      the first 40,000 years of human evolution, and thus future research should
      investigate the effects of this abundance upon the mechanisms regulating
      activity. 

PMID- 24455729
TI  - Prognostic significance of immunohistochemical phenotypes in patients treated for
      high-grade cervical intraepithelial neoplasia.
AB  - Strong evidence exists that the host's immune system plays a crucial role for the
      development of human papillomavirus-related cervical premalignant and malignant
      lesions. In particular, effective cell-mediated immunity (CMI) promotes
      spontaneous infection clearance and cancer precursors regression in healthy
      subjects, while immunosuppressed individuals are more likely to experience
      infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and
      cervical cancer. In this study, the prognostic significance of
      immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells
      (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical
      specimens of 34 consecutive women affected by high-grade cervical intraepithelial
      neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated
      with the clinical outcomes at 24 months after treatment and statistically
      analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+
      transcription factor positivity showed a strong statistically significative
      correlation with favourable clinical outcomes (P <= 0.0001). These data reinforce
      the evidence of the relevance of the host's immune status in the natural history
      of HPV-related cervical disease and add a prognostic significance of the cervical
      immunological profile in terms of predicting significant lower recurrence rates. 

PMID- 24455730
TI  - Cellular performance comparison of biomimetic calcium phosphate coating and
      alkaline-treated titanium surface.
AB  - The influence of biomimetic calcium phosphate coating on osteoblasts behavior in
      vitro is not well established yet. In this study, we investigated the behavior of
      osteoblastic rat osteosarcoma 17/2.8 cells (ROS17/2.8) on two groups of
      biomaterial surfaces: alkaline-treated titanium surface (ATT) and biomimetic
      calcium phosphate coated ATT (CaP). The cell attachment, proliferation,
      differentiation, and morphology on these surfaces were extensively evaluated to
      reveal the impact of substrate surface on osteoblastic cell responses. It was
      found that the ROS17/2.8 cells cultured on the ATT surface had higher attachment
      and proliferation rates compared to those on the CaP surface. Our results also
      showed that the calcium phosphate coatings generated in this work have an
      inhibiting effect on osteoblast adhesion and further influenced the proliferation
      and differentiation of osteoblast compared to the ATT surface in vitro. Cells on
      the ATT surface also exhibited a higher alkaline phosphatase activity than on the
      CaP surface after two weeks of culture. Immunofluorescence staining and scanning
      electron microscopy results showed that the cells adhered and spread faster on
      the ATT surface than on the CaP surface. These results collectively suggested
      that substrate surface properties directly influence cell adhesion on different
      biomaterials, which would result in further influence on the cell proliferation
      and differentiation. 

PMID- 24455731
TI  - Complex assessment of the incidence and risk factors of delirium in a large
      cohort of cardiac surgery patients: a single-center 6-year experience.
AB  - BACKGROUND: Previous reports provided inconsistent data on the occurrence of
      postoperative delirium and emphasized its considerable impact on outcome. This
      study sought to evaluate the incidence and predictors of delirium, together with
      its relation to cerebral ischemia in a large cohort of cardiac surgery patients
      in a tertiary high-volume center. METHODS AND RESULTS: Consecutive patients (n =
      8792) were prospectively enrolled from 2003 to 2008. Exclusion criteria were
      history of psychiatric disorders, use of psychoactive drugs, alcohol abuse, and
      data incompleteness. Finally, 5781 patients were analyzed in terms of 100
      perioperative patient-specific and treatment variables. The incidence of
      postoperative delirium (DSM IV criteria) was 4.1% and it coexisted with cerebral
      ischemia in 1.1% of patients. In bivariate analysis, 49 variables were
      significantly linked to postoperative delirium. Multivariate analysis confirmed
      that delirium was independently associated with postoperative stroke (logistic
      odds ratio (logOR) = 2.862, P = 0.004), any blood transfusions (logOR = 4.178, P
      < 0.0001), age > 65 years (logOR = 2.417, P = 0.002), carotid artery stenosis
      (logOR = 2.15, P = 0.01), urgent/emergent surgery (logOR = 1.982, P = 0.02),
      fasting glucose level, intraoperative oxygen partial pressure fluctuations, and
      hematocrit. Area under ROC curve for the model was 0.8933. CONCLUSIONS: Early
      identification of nonpsychiatric perioperative determinants of delirium
      facilitates its diagnosis and might help develop preventive strategies to improve
      long-term outcome after cardiac surgery procedures.

PMID- 24455732
TI  - Presymptomatic treatment with acetylcholinesterase antisense oligonucleotides
      prolongs survival in ALS (G93A-SOD1) mice.
AB  - OBJECTIVE: Previous research suggests that acetylcholinesterase (AChE) may be
      involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE
      transcription which in certain contexts can have deleterious (noncatalytic)
      effects, making them theoretically harmful in ALS, whilst AChE antisense
      oligonucleotides (mEN101), which downregulate AChE may be beneficial. Our aim was
      to investigate whether downregulation of AChE using mEN101 is beneficial in an
      ALS mouse model. METHODS: ALS (G93A-SOD1) mice received saline, mEN101, inverse
      EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset
      and survival were recorded. Additional mice were sacrificed for pathological
      analysis at 15 weeks of age. In a follow-up experiment treatment was started at
      the symptomatic stage at a higher dose. RESULTS: mEN101 given at the
      presymptomatic (but not symptomatic) stage prolonged survival and attenuated
      motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical
      parameters. CONCLUSIONS: These results suggest that AChE may be involved in ALS
      pathogenesis. The accelerated disease course with neostigmine suggests that any
      beneficial effects of mEN101 occur through a non-catalytic rather than
      cholinergic mechanism.

PMID- 24455733
TI  - Risk factors for the first episode of Klebsiella pneumoniae resistant to
      carbapenems infection in critically ill patients: a prospective study.
AB  - OBJECTIVE: To identify risk factors for the first episode of Klebsiella Pneumonia
      resistant to carbapenems (KPRC) infection in critically ill patients. DESIGN,
      SETTING, AND METHODS: This prospective cohort study was conducted in a 12-bed
      general Intensive Care Unit (ICU) in a University Hospital on ICU patients who
      required mechanical ventilation (MV) for >48 hours during a 12-month period.
      Clinical and microbiologic data were studied. Characteristics of KPRC patients
      were compared with those of critically ill patients who presented nonmultidrug
      resistant (MDR) bacterial infections or no documented infection at all. RESULTS:
      Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial
      infection, and 39 patients presented no infection. Compared to patients without
      documented infection or infected by non MDR bacteria, patients with KPRC
      infection had received more frequently or for longer duration antibiotics against
      Gram-negative bacteria (carbapenems, colistin P < 0.05). Duration of colistin
      administration prior to KPRC isolation was independently associated with
      increased frequency of KPRC infection (odds ratio, 1.156 per day; 95% confidence
      interval, 1.010 to 1.312; P = 0.025). KPRC patients stayed longer in the ICU and
      received mechanical ventilation and sedation for longer periods and presented
      increased mortality (P < 0.05). CONCLUSION: KPRC infection is an emerging problem
      which might be more common in patients with previous use of antibiotics and
      especially colistin.

PMID- 24455734
TI  - Genotyping of clinical Mycobacterium tuberculosis isolates based on IS6110 and
      MIRU-VNTR polymorphisms.
AB  - In this study, 155 clinical Mycobacterium tuberculosis isolates were subject to
      genotyping with fast ligation-mediated PCR (FLiP). This typing method is a
      modified mixed-linker PCR, a rapid approach based on the PCR amplification of
      HhaI restriction fragments of genomic DNA containing the 3' end of IS6110 and
      resolving the amplicons by polyacrylamide gel electrophoresis. The results were
      compared with previous data of the more commonly used methods, 15-locus
      mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU
      VNTR) typing and, to verify combined FLiP/MIRU-VNTR clusters, the reference
      IS6110 restriction fragment length polymorphism (RFLP). FLiP banding patterns
      were highly reproducible and polymorphic. This method differentiated 119 types
      among the study set compared to 108 distinct MIRU-VNTR profiles. The
      discriminatory power of FLiP was slightly higher than that of MIRU-VNTR analysis
      (Hunter-Gaston Discriminatory Index = 0.991 and 0.990, resp.). Detailed
      comparison of the clusters defined by each of the methods revealed, however, a
      more apparent difference in the discriminatory abilities that favored FLiP.
      Clustering of strains by using combined results of these two PCR-based methods
      correlated well with IS6110 RFLP-defined clusters, further confirming high
      discriminatory potential of FLiP typing. These results indicate that FLiP could
      be an attractive and valuable secondary typing technique for verification of MIRU
      VNTR clusters of M. tuberculosis strains.

PMID- 24455735
TI  - Effect of paracetamol, dexketoprofen trometamol, lidocaine spray, and
      paracervical block application for pain relief during suction termination of
      first-trimester pregnancy.
AB  - The aim of the study was to investigate the analgesic efficacy of preoperative
      oral dexketoprofen trometamol, intravenous paracetamol, lidocaine spray, and
      paracervical block with ultracaine on curettage procedure. A total of 111
      subjects with the request of pregnancy termination between 5 and 7 weeks of
      gestation were included in the study. The first group (control group) consisted
      of 20 participants without medication. The second group consisted of 25
      participants receiving 2 puffs of lidocaine sprays on cervical mucosa. The third
      group consisted of 20 participants receiving oral 25 mg dexketoprofen trometamol.
      The fourth group consisted of 23 participants receiving 1000 mg intravenous
      paracetamol and the fifth group consisted of 23 participants receiving
      paracervical block with ultracaine. Paracervical block reduced pain score
      significantly in both intraoperative and postoperative periods. All analgesic
      procedures were significantly effective for reducing pain in postoperative
      period. Paracervical block may be the best method for reducing pain scores in
      intraoperative and postoperative periods during curettage procedure. All
      analgesic procedures such as lidocaine, paracetamol, ultracaine, and paracervical
      block with ultracaine can be used for reducing pain score in postoperative
      period. This trial is registered with NCT01947205.

PMID- 24455736
TI  - Sedation of newborn infants for the INSURE procedure, are we sure?
AB  - BACKGROUND: Neonatal intubation is a stressful procedure that requires
      premedication to improve intubation conditions and reduce stress and adverse
      physiological responses. Premedication used during the INSURE (INtubation,
      SURfactant therapy, Extubation) procedure should have a very short duration of
      action with restoration of spontaneous breathing within a few minutes. AIMS: To
      determine the best sedative for intubation during the INSURE procedure by
      systematic review of the literature. METHODS: We reviewed all relevant studies
      reporting on premedication, distress, and time to restoration of spontaneous
      breathing during the INSURE procedure. RESULTS: This review included 12 studies:
      two relatively small studies explicitly evaluated the effect of premedication
      (propofol and remifentanil) during the INSURE procedure, both showing good
      intubation conditions and an average extubation time of about 20 minutes. Ten
      studies reporting on fentanyl or morphine provided insufficient information about
      these items. CONCLUSIONS: Too little is known in the literature to draw a solid
      conclusion on which premedication could be best used during the INSURE procedure.
      Both remifentanil and propofol are suitable candidates but dose-finding studies
      to detect effective nontoxic doses in newborns with different gestational ages
      are necessary.

PMID- 24455737
TI  - Wound-healing potential of Cultured Epidermal Sheets is unaltered after
      lyophilization: a preclinical study in comparison to cryopreserved CES.
AB  - Lyophilized Cultured Epidermal Sheets (L-CES) have been reported to be as
      effective as the cryopreserved CES (F-CES) in treating skin ulcers. However,
      unlike F-CES, no preclinical study assessing wound-healing effects has been
      conducted for L-CES. The present study was set out to investigate the
      microstructure, cytokine profile, and wound-healing effects of L-CES in
      comparison to those of F-CES. Keratinocytes were cultured to prepare CES,
      followed by cryopreservation at -70  degrees C and lyophilization. Under
      microscopic observation, intact cells with apparent intracellular junctions were
      observed in L-CES. The L-CES, like fresh CES, consisted of three to four well
      maintained epidermal layers, as shown by the expression of keratins, involucrin,
      and p63. There were no differences in the epidermal layer or protein expression
      between L-CES and F-CES, and both CES were comparable to fresh CES. TGF-alpha,
      EGF, VEGF, IL-1alpha, and MMPs were detected in L-CES at levels similar to those
      in F-CES. In a mouse study, wounds treated with L-CES or F-CES completely healed
      at least 4 days faster than untreated wounds. CES-treated wounds completely
      healed by day 10, while the untreated wounds did not heal by day 14. Masson's
      trichrome staining showed that collagen deposition in the CES-treated wounds was
      highly increased in the dermis of the wound center compared to that in the
      control wounds. Thus, this study demonstrates that L-CES is as clinically
      effective as F-CES for wound treatment.

PMID- 24455738
TI  - Different effects of the immunomodulatory drug GMDP immobilized onto aminopropyl
      modified and unmodified mesoporous silica nanoparticles upon peritoneal
      macrophages of women with endometriosis.
AB  - The aim of the present work was to compare in vitro the possibility of
      application of unmodified silica nanoparticles (UMNPs) and modified by
      aminopropyl groups silica nanoparticles (AMNPs) for topical delivery of
      immunomodulatory drug GMDP to the peritoneal macrophages of women with
      endometriosis. The absence of cytotoxic effect and high cellular uptake was
      demonstrated for both types of silica nanoparticles. The immobilization of GMDP
      on the UMNPs led to the suppression of the stimulatory effect of GMDP on the
      membrane expression of scavenger receptors SR-AI and SR-B, mRNAs expression of
      NOD2 and RAGE, and synthesis of proteolytic enzyme MMP-9 and its inhibitor TIMP
      1. GMDP, immobilized onto AMNPs, enhanced the initially reduced membrane
      expression of SRs and increased NOD2, RAGE, and MMP-9 mRNAs expression by
      macrophages. Simultaneously high level of mRNAs expression of factors, preventing
      undesirable hyperactivation of peritoneal macrophages (SOCS1 and TIMP-1), was
      observed in macrophages incubated in the presence of GMDP, immobilized onto
      AMNPs. The effect of AMNPs immobilized GMDP in some cases exceeded the effect of
      free GMDP. Thus, among the studied types of silica nanoparticles, AMNPs are the
      most suitable nanoparticles for topical delivery of GMDP to the peritoneal
      macrophages. 

PMID- 24455739
TI  - Lactobacilli reduce chemokine IL-8 production in response to TNF-alpha and
      Salmonella challenge of Caco-2 cells.
AB  - The probiotic properties of two selected lactobacilli strains were assessed. L.
      salivarius and L. plantarum displayed higher hydrophobicity (48% and 54%, resp.)
      and coaggregation ability with four pathogens (from 7.9% to 57.5%). L. salivarius
      and L. plantarum had good inhibitory effects on S. aureus (38.2% and 49.5%,
      resp.) attachment to Caco-2 cells. Live lactobacilli strains and their
      conditioned media effectively inhibited IL-8 production (<14.6 pg/mL) in TNF
      alpha-induced Caco-2 cells. Antibiotic-treated and the sonicated lactobacilli
      also maintained inhibitory effects (IL-8 production from 5.0 to 36.3 pg/mL);
      however, the heat-treated lactobacilli lost their inhibitory effects (IL-8
      production from 130.2 to 161.0 pg/mL). These results suggest that both the
      structural components and the soluble cellular content of lactobacilli have anti
      inflammatory effects. We also found that pretreatment of Caco-2 cells with
      lactobacilli inhibited S. typhimurium-induced IL-8 production (<27.3 pg/mL).
      However, lactobacilli did not inhibit IL-8 production in Caco-2 cells pretreated
      with S. typhimurium. These results suggest that the tested lactobacilli strains
      are appropriate for preventing inflammatory diseases caused by enteric pathogens
      but not for therapy. In short, L. salivarius and L. plantarum are potential
      candidates for the development of microbial ecological agents and functional
      foods.

PMID- 24455740
TI  - DPYD, TYMS, TYMP, TK1, and TK2 genetic expressions as response markers in locally
      advanced rectal cancer patients treated with fluoropyrimidine-based
      chemoradiotherapy.
AB  - This study is to investigate multiple chemotherapeutic agent- and radiation
      related genetic biomarkers in locally advanced rectal cancer (LARC) patients
      following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response
      prediction. We initially selected 6 fluoropyrimidine metabolism-related genes
      (DPYD, ORPT, TYMS, TYMP, TK1, and TK2) and 3 radiotherapy response-related genes
      (GLUT1, HIF-1alpha, and HIF-2alpha) as targets for gene expression identification
      in 60 LARC cancer specimens. Subsequently, a high-sensitivity weighted enzymatic
      chip array was designed and constructed to predict responses following CCRT.
      After CCRT, 39 of 60 (65%) LARC patients were classified as responders
      (pathological tumor regression grade 2 ~ 4). Using a panel of multiple genetic
      biomarkers (chip), including DPYD, TYMS, TYMP, TK1, and TK2, at a cutoff value
      for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were
      obtained (AUC: 0.915; 95% CI: 0.840-0.991). Negative chip results were
      significantly correlated to poor CCRT responses (TRG 0-1) (P = 0.014, hazard
      ratio: 22.704, 95% CI: 3.055-235.448 in multivariate analysis). Disease-free
      survival analysis showed significantly better survival rate in patients with
      positive chip results (P = 0.0001). We suggest that a chip including DPYD, TYMS,
      TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC
      following fluoropyrimidine-based CCRT.

PMID- 24455741
TI  - Role of omega-3 polyunsaturated fatty acids in the production of prostaglandin E2
      and nitric oxide during experimental murine paracoccidioidomycosis.
AB  - There has recently been increased interest in the potential health effects of
      omega-3 polyunsaturated fatty acids on the immune system. Paracoccidioidomycosis
      is the most important endemic mycosis in Latin America. Macrophages have a
      fundamental role and act as first line of organism defense. The purpose of this
      study was to analyze the effect of n-3 fatty acids on the production of PGE2 and
      NO by mice infected with Pb18 and fed a diet enriched with LNA for 8 weeks. To
      study the effect of omega-3 fatty acids on macrophage activity during
      experimental paracoccidioidomycosis, mice were infected with Pb18 and fed a diet
      supplemented with LNA. PGE2 in the serum of animals was analyzed and NO in the
      supernatants of macrophages cultured and challenged in vitro with Pb18 was
      measured. Omega-3 fatty acids seemed to decrease the production of PGE2 in vivo
      in the infected group fed an LNA-supplemented diet during the 4th and 8th weeks
      of the experiment. At the same time, we observed an increase in synthesis of NO
      by peritoneal macrophages in this group. Omega-3 fatty acids thus appear to have
      an immunomodulatory effect in paracoccidioidomycosis. 

PMID- 24455742
TI  - Alterations in hair follicle dynamics in women.
AB  - Endocrine changes supervening after parturition and menopause participate in the
      control of sebum production and hair growth modulation. The ensuing conditions
      include some peculiar aspects of hair loss (effluvium), alopecia, and facial
      hirsutism. The hair cycling is of major clinical relevance because most hair
      growth disorders result from disturbances in this chronobiological feature. Of
      note, any correlation between a biologic abnormality and hair cycling disturbance
      does not prove a relationship of causality. The proportion of postmenopausal
      women is rising in the overall population. Therefore, the prevalence of these
      hair follicle disturbances is globally on the rise. Current therapies aim at
      correcting the underlying hormonal imbalances, and at improving the overall
      cosmetic appearance. However, in absence of pathogenic diagnosis and causality
      criteria, chances are low that a treatment given by the whims of fate will
      adequately control hair effluvium. The risk and frequency of therapeutic inertia
      are further increased. When the hair loss is not controlled and/or compensated by
      growth of new hairs, several clinical aspects of alopecia inexorably develop.
      Currently, there is little evidence supporting any specific treatment for these
      endocrine hair disorders in post-partum and postmenopausal women. Current hair
      treatment strategies are symptomatic and nonspecific so current researchers aim
      at developing new, targeted methods. 

PMID- 24455743
TI  - Biologic activity and biotechnological development of natural products.

PMID- 24455744
TI  - Revisiting the cutaneous impact of oral hormone replacement therapy.
AB  - Menopause is a key point moment in the specific aging process of women. It
      represents a universal evolution in life. Its initiation is defined by a 12-month
      amenorrhea following the ultimate menstrual period. It encompasses a series of
      different biologic and physiologic characteristics. This period of life appears
      to spot a decline in a series of skin functional performances initiating tissue
      atrophy, withering, and slackness. Any part of the skin is possibly altered,
      including the epidermis, dermis, hypodermis, and hair follicles. Hormone
      replacement therapy (oral and nonoral) and transdermal estrogen therapy represent
      possible specific managements for women engaged in the climacteric phase. All the
      current reports indicate that chronologic aging, climacteric estrogen deficiency,
      and adequate hormone therapy exert profound effects on various parts of the skin.

PMID- 24455745
TI  - A glimpse of the pathogenetic mechanisms of Wnt/beta-catenin signaling in
      diabetic nephropathy.
AB  - The Wnt family of proteins belongs to a group of secreted lipid-modified
      glycoproteins with highly conserved cysteine residues. Prior results indicate
      that Wnt/beta-catenin signaling plays a prominent role in cell differentiation,
      adhesion, survival, and apoptosis and is involved in organ development,
      tumorigenesis, and tissue fibrosis, among other functions. Accumulating evidence
      has suggested that Wnt/beta-catenin exhibits a pivotal function in the
      progression of diabetic nephropathy (DN). In this review, we focused on
      discussing the dual role of Wnt/beta-catenin in apoptosis and epithelial
      mesenchymal transition (EMT) formation of mesangial cells. Moreover, we also
      elucidated the effect of Wnt/beta-catenin in podocyte dysfunction, tubular EMT
      formation, and renal fibrosis under DN conditions. In addition, the molecular
      mechanisms involved in this process are introduced. This information provides a
      novel molecular target of Wnt/beta-catenin for the protection of kidney damage
      and in delay of the progression of DN.

PMID- 24455746
TI  - The role of autophagy in the pathogenesis of diabetic nephropathy.
AB  - Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The
      multipronged drug approach targeting blood pressure and serum levels of glucose,
      insulin, and lipids fails to fully prevent the onset and progression of diabetic
      nephropathy. Therefore, a new therapeutic target to combat diabetic nephropathy
      is required. Autophagy is a catabolic process that degrades damaged proteins and
      organelles in mammalian cells and plays a critical role in maintaining cellular
      homeostasis. The accumulation of proteins and organelles damaged by hyperglycemia
      and other diabetes-related metabolic changes is highly associated with the
      development of diabetic nephropathy. Recent studies have suggested that autophagy
      activity is altered in both podocytes and proximal tubular cells under diabetic
      conditions. Autophagy activity is regulated by both nutrient state and
      intracellular stresses. Under diabetic conditions, an altered nutritional state
      due to nutrient excess may interfere with the autophagic response stimulated by
      intracellular stresses, leading to exacerbation of organelle dysfunction and
      diabetic nephropathy. In this review, we discuss new findings showing the
      relationships between autophagy and diabetic nephropathy and suggest the
      therapeutic potential of autophagy in diabetic nephropathy.

PMID- 24455748
TI  - Effects of acute exercise and chronic exercise on the liver leptin-AMPK-ACC
      signaling pathway in rats with type 2 diabetes.
AB  - AIM: To investigate the effects of acute and chronic exercise on glucose and
      lipid metabolism in liver of rats with type 2 diabetes caused by a high fat diet
      and low dose streptozotocin (STZ). METHODS: Animals were classified into control
      (CON), diabetes (DC), diabetic chronic exercise (DCE), and diabetic acute
      exercise (DAE) groups. RESULTS: Compared to CON, the leptin levels in serum and
      liver and ACC phosphorylation were significantly higher in DC, but the levels of
      liver leptin receptor, AMPK alpha 1/2, AMPK alpha 1, and ACC proteins expression
      and phosphorylation were significantly lower in DC. In addition, the levels of
      liver glycogen reduced significantly, and the levels of TG and FFA increased
      significantly in DC compared to CON. Compared to DC, the levels of liver AMPK
      alpha 1/2, AMPK alpha 2, AMPK alpha 1, and ACC phosphorylation significantly
      increased in DCE and DAE. However, significant increase of the level of liver
      leptin receptor and glycogen as well as significant decrease of the level of TG
      and FFA were observed only in DEC. CONCLUSION: Our study demonstrated that both
      acute and chronic exercise indirectly activated the leptin-AMPK-ACC signaling
      pathway and increased insulin sensitivity in the liver of type 2 diabetic rats.
      However, only chronic and long-term exercise improved glucose and lipid
      metabolism of the liver.

PMID- 24455747
TI  - Early life factors and type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and its aetiology
      involves a complex interplay between genetic, epigenetic, and environmental
      factors. In recent years, evidences from both human and animal experiments have
      correlated early life factors with programming diabetes risk in adult life. Fetal
      and neonatal period is crucial for organ development. Many maternal factors
      during pregnancy may increase the risk of diabetes of offsprings in later life,
      which include malnutrition, healthy (hyperglycemia and obesity), behavior
      (smoking, drinking, and junk food diet), hormone administration, and even stress.
      In neonates, catch-up growth, lactation, glucocorticoids administration, and
      stress have all been found to increase the risk of insulin resistance or T2DM.
      Unfavorable environments (socioeconomic situation and famine) or obesity also has
      long-term negative effects on children by causing increased susceptibility to
      T2DM in adults. We also address the potential mechanisms that may underlie the
      developmental programming of T2DM. Therefore, it might be possible to prevent or
      delay the risk for T2DM by improving pre- and/or postnatal factors. 

PMID- 24455750
TI  - The Influences of Pre-testing Reviews and Delays on Differentialassociative
      Processing versus A Condition in which Students chose their Learning Strategy.
AB  - Recent studies show that a new strategy called differential-associative
      processing is effective for learning related concepts. However our knowledge
      about differential-associative processing is still limited. Therefore the goals
      of the present study are to assess the duration of knowledge that is acquired
      from using differential-associative processing, to determine whether the efficacy
      of differential-associative processing changes with the addition of a 10-minute
      pre-testing review, and to compare differential-associate processing to two
      conditions in which students select their own learning strategy. The results
      revealed that differential-associative processing was a better strategy for
      learning related concepts than were either of the two comparison conditions. They
      also revealed that a 10-minute pre-testing review had a positive additive
      influence on differential-associative processing. Finally, although the knowledge
      acquired from using differential-associative processing declined with an increase
      in delay between learning and testing, this decline was equivalent to the decline
      observed in both comparison conditions.

PMID- 24455749
TI  - Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene
      expression profiling in multiple tissues or cells.
AB  - Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in
      recent years. Recent studies have focused on identifying causal variations or
      candidate genes for obesity and T2DM via analysis of expression quantitative
      trait loci (eQTL) within a single tissue. T2DM and obesity are affected by
      comprehensive sets of genes in multiple tissues. In the current study, gene
      expression levels in multiple human tissues from GEO datasets were analyzed, and
      21 candidate genes displaying high percentages of differential expression were
      filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3,
      HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K,
      CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and
      TOMM5 were identified from the obesity-control study. The majority of these genes
      are known to be involved in T2DM and obesity. Therefore, analysis of gene
      expression in various tissues using GEO datasets may be an effective and feasible
      method to determine novel or causal genes associated with T2DM and obesity. 

PMID- 24455751
TI  - Tackling Primary Cilia Dysfunction in Photoreceptor Degenerative Diseases of the
      Eye.

PMID- 24455754
TI  - Quantitative Methods for Valuing Comparative Effectiveness Information.

PMID- 24455752
TI  - Antigen-specific bacterial vaccine combined with anti-PD-L1 rescues dysfunctional
      endogenous T cells to reject long-established cancer.
AB  - Immunogenic tumors grow progressively even when heavily infiltrated by CD8(+) T
      cells. We investigated how to rescue CD8(+) T cell function in long-established
      immunogenic melanomas that contained a high percentage of endogenous PD-1(+)
      tumor-specific CD8(+) T cells that were dysfunctional. Treatment with alphaPD-L1
      and alphaCTLA-4 blocking antibodies did not prevent tumors from progressing
      rapidly. We then tested exogenous tumor-specific antigen delivery into tumors
      using Salmonella Typhimurium A1-R to increase antigen levels and generate a
      proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the
      endogenous tumor-specific CD8(+) T cell response: proliferation was induced in
      the lymphoid organs and effector function was recovered in the tumor. Treatment
      with antigen-producing A1-R led to improved mouse survival and resulted in 32%
      rejection of long-established immunogenic melanomas. Following treatment with
      antigen-producing A1-R, the majority of tumor-specific CD8(+) T cells still
      expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R
      with alphaPD-L1 blocking antibody enhanced the expansion of tumor-specific CD8(+)
      T cells and resulted in 80% tumor rejection. Collectively, these data demonstrate
      a powerful new therapeutic approach to rescue dysfunctional endogenous tumor
      specific CD8(+) T cells and eradicate advanced immunogenic tumors. 

PMID- 24455755
TI  - Development of a Mobile User Interface for Image-based Dietary Assessment.
AB  - In this paper, we present a mobile user interface for image-based dietary
      assessment. The mobile user interface provides a front end to a client-server
      image recognition and portion estimation software. In the client-server
      configuration, the user interactively records a series of food images using a
      built-in camera on the mobile device. Images are sent from the mobile device to
      the server, and the calorie content of the meal is estimated. In this paper, we
      describe and discuss the design and development of our mobile user interface
      features. We discuss the design concepts, through initial ideas and
      implementations. For each concept, we discuss qualitative user feedback from
      participants using the mobile client application. We then discuss future designs,
      including work on design considerations for the mobile application to allow the
      user to interactively correct errors in the automatic processing while reducing
      the user burden associated with classical pen-and-paper dietary records.

PMID- 24455753
TI  - Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor
      progression.
AB  - CD8 T lymphocytes are able to eliminate nascent tumor cells through a process
      referred to as immune surveillance. However, multiple inhibitory mechanisms
      within the tumor microenvironment have been described that impede tumor rejection
      by CD8 T cells, including increased signaling by inhibitory receptors.
      Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that has been shown
      repeatedly to promote diverse cellular processes benefiting tumorigenesis.
      Accordingly, the increased expression of LPA and LPA receptors is a common
      feature of diverse tumor cell lineages and can result in elevated systemic LPA
      levels. LPA is recognized by at least 6 distinct G-protein-coupled receptors and
      several of which are expressed by T cells, although the precise role of LPA
      signaling in CD8 T cell activation and function has not been defined. Here, we
      demonstrate that LPA signaling via the LPA5 receptor expressed by CD8 T cells
      suppresses antigen receptor signaling, cell activation and proliferation in vitro
      and in vivo. Importantly, in a mouse melanoma model tumor-specific CD8 T cells
      that are LPA5-deficient are able to control tumor growth significantly better
      than wild-type tumor-specific CD8 T cells. Together, these data suggest that the
      production of LPA by tumors serves not only in an autocrine manner to promote
      tumorigenesis but also as a mechanism to suppress adaptive immunity and
      highlights a potential novel target for cancer treatment. 

PMID- 24455756
TI  - The correlation analysis of WWOX expression and cancer related genes in
      neuroblastoma- a real time RT-PCR study.
AB  - Neuroblastoma is one of the most common paediatric cancers, described as
      unpredictable due to diverse patterns of behaviour. WWOX is a tumour suppressor
      gene whose expression is reduced in many tumour types. Loss of its expression was
      shown to correlate with more aggressive disease stage and mortality rate. The aim
      of this study was to investigate the role of the WWOX tumour suppressor gene in
      neuroblastoma formation. We performed real-time RT-PCR to analyse levels of WWOX
      expression in 22 neuroblastic tumour samples in correlation with genes involved
      in cell cycle regulation (CCNE1, CCND1), proliferation (MKI67), apoptosis (BCL2,
      BIRC5, BAX) and signal transduction (EGFR, ERBB4). We also evaluated two
      potential mechanisms - promoter methylation (MethylScreen method) and loss of
      heterozygosity (LOH) status, which could be connected with regulation of WWOX
      gene expression. We found a positive correlation between WWOX gene and BCL2 and
      HER4 JM-a and negative with cyclin D1 and E1. Our observations are consistent
      with previous findings and emphasise the role of WWOX in cell cycle and apoptosis
      regulation. Moreover, strong positive association with HER4 JM-a in this tumour
      type may indicate a role for WWOX in neuroblastoma cell differentiation. The
      presented results indicate that LOH in locus D16S3096 (located in intron 8) may
      be involved in the regulation of WWOX mRNAexpression. However, no association
      between methylation status of WWOX promoter and its expression was observed. 

PMID- 24455757
TI  - Activation of MAP kinase pathways in Galleria mellonella infected with Bacillus
      thuringiensis.
AB  - We followed changes in the level of phospho-MAP kinases in the greater wax moth
      Galleria mellonella after infection with Bacillus thuringiensis. We observed an
      enhanced level of phosphorylated p38 and JNK in fat bodies of the infected
      larvae. In hemocytes, injection of B. thuringiensis caused the highest increase
      in phospho-JNK, however, all pathways were activated after aseptic injection. We
      report that Galleria mellonella larvae exposed to heat shock before infection
      showed an enhanced level of phosphorylated JNK in fat body. This finding is
      relevant in the light of our previous reports, which submit evidence that pre
      shocked animals are more resistant to infection. 

PMID- 24455758
TI  - Thermodynamic aspects of the self-assembly of DsrA, a small noncoding RNA from
      Escherichia coli.
AB  - DsrA is an Escherichia coli small noncoding RNA that acts by base pairing to some
      mRNAs in order to control their translation and turnover. It was recently shown
      that DsrA is able to self-associate in a way similar to DNA and to build
      nanostructures. Although functional consequence of this RNA self-assembly in vivo
      is not yet understood, the formation of such an assemblage more than likely
      influences the noncoding RNA function. We report here for the first time the
      thermodynamic basis of this natural RNA self-assembly. In particular we show that
      assembling of the ribonucleic acid is enthalpy driven and that the versatility of
      the RNA molecule is important for the polymerisation; indeed, an equivalent DNA
      sequence is unable to make a nanoassembly. The origin of the difference is
      discussed herein. 

PMID- 24455759
TI  - Adipocyte response to conjugated linoleic acid.
AB  - Conjugated linoleic acid (CLA), which is a generic term to describe isomers of
      octadecadienoic acid, has been reported to exert various beneficial physiological
      effects. Accumulating data show that CLA, especially trans10, cis12 (t10, c12)
      CLA, has a potent body fat-reducing effect, which is prominent in mice and to a
      lesser extent rats. In addition, several clinical studies have demonstrated the
      body fat- and weight-reducing effect of CLA in humans. However, t10, c12-CLA
      evokes severe lipodystrophy in mice that results in impaired glucose metabolism.
      Therefore, while CLA is a promising agent for the amelioration of obesity and
      obesity-related diseases, it is important to establish its safety prior to common
      use in humans. In addition, it is important to elucidate the details of the
      molecular mechanisms of CLA. Here, we focus on the response of adipocyte to CLA.

PMID- 24455760
TI  - The roles of salivary secretion, brain-gut peptides, and oral hygiene in obesity.
AB  - Obesity has a prevalence of 15-30% among European and American populations. It is
      an incurable chronic disease associated with considerable mortality and co
      morbidity. The co-morbidity risk can be reduced substantially by a moderate
      weight loss of 5-15%. Notably, additional weight gain exacerbates the morbidity
      of any concurrent disease. Obesity is also recognized as the basis for metabolic
      syndrome. Recent research has shown that adipocytes secrete various hormones and
      cytokines that contribute to obesity. Leptin is an adipostatic hormone that acts
      on receptors in the hypothalamus to suppress food intake and increase energy
      consumption. Reduced sensitivity to this molecule can trigger the onset of
      obesity. Neuropeptides such as leptin also affect salivary secretion. Various
      neuropeptides have been identified in saliva; the associated receptors are
      located in the salivary glands or in the nerves innervating the salivary glands.
      Obesity is associated with hyposalivation and thereby related to several aspects
      of oral health, such as caries and periodontitis. Hyposalivation is a severe
      morbidity that can lead to a precipitous decline in oral hygiene, which further
      leads to multifocal dental caries and periodontitis, or even cardiac disorders.
      In this article, we review the relationship between salivary secretion and
      neuropeptides known to play a role in obesity.

PMID- 24455761
TI  - Increased oxidative stress in obesity: implications for metabolic syndrome,
      diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer.
AB  - Obesity, especially of the abdominal type, is a health problem that constitutes
      metabolic syndrome and increases the incidence of various diseases, including
      diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Various
      mechanisms linking obesity to these associated diseases have been postulated. One
      candidate is oxidative stress, which has been implicated in vascular
      complications of diabetes and in pancreatic -cell failure in diabetes. Notably,
      obese people without diabetes also display elevated levels of systemic oxidative
      stress. In addition, levels of oxidative stress are increased in the adipose
      tissue in obese mice. Treating obese mice with antioxidant agents attenuates the
      development of diabetes. In 3T3-L1 adipocytes, increases in reactive oxygen
      species (ROS) occur with lipid accumulation; the addition of free fatty acids
      elevates ROS generation further. Thus, adipose tissue represents an important
      source of ROS; ROS may contribute to the development of obesity-associated
      insulin resistance and type 2 diabetes. Moreover, the levels of oxidative stress
      present in several other types of cells or tis-sues, including those in the
      brain, arterial walls, and tumors, have been implicated in the pathogenesis
      associated with hypertension, atherosclerosis, and cancer. The increased levels
      of systemic oxidative stress that occur in obesity may contribute to the obesity
      associated development of these diseases.

PMID- 24455762
TI  - Effects of hydrophilic statins on renal tubular lipid accumulation in diet
      induced obese mice.
AB  - Animal models of obesity show that lipid deposits can injure the kidneys,and
      there is evidence for the role of lipids in the development of chronic renal dis
      ease (CKD). Statins exhibit a lipid-lowering effect that acts on both total
      cholesterol and triglyceride (TG) levels and pleiotropic effects including their
      ability to reduce inflammation and fibrosis. The purpose of the present study was
      to confirm whether obesity induced by a high-fat diet (HFD, 60% fat) promotes
      lipid accumulation in the tubulointerstitial and/or glomerular areas in the
      kidney, and whether treatment of several statins, pravastatin (30 mg/kg, p.o.),
      rosuvastatin (3 mg/kg, p.o.),pitavastatin (1 mg/kg, p.o.) and atorvastatin (10
      mg/kg, p.o.), suppresses obesity-induced lipid accumulation. Using male C57Bl/6J
      mice, we examined parameters related to energy metabolism, lipid accumulation as
      well as macrophage infiltration in glomeruli and the tubulointerstitial area, and
      glomerular injury using nephrin and desmin expression. None of the statins
      affected body weight, glucose metabolism,serum TG and adiponectin levels, or
      serum inflammatory cytokine levels. However,all statins improved lipid
      accumulation in the proximal tubules, improved glomerular hypertrophy, increased
      nephrin expression and decreased desmin expression, compared to non-treated obese
      animals. Moreover, the reduction of proximal tubular lipid accumulation was
      greater with pravastatin and rosuvastatin treatment than with pitavastatin and
      atorvastatin treatment. We concluded that hydrophilic statins may be more
      effective for preventing lipid accumulation in renal tubules than lipophilic
      statins.

PMID- 24455764
TI  - Abstracts of the 27th Annual Meeting of the European Association for Cardio
      Thoracic Surgery. Vienna, Austria. October 5-9. 2013.

PMID- 24455763
TI  - Activation of peroxisome proliferator-activated receptor-alpha (PPARalpha) in
      proximal intestine improves postprandial lipidemia in obese diabetic KK-Ay mice.
AB  - Postprandial lipidemia is a risk factor for cardiovascular diseases. Thus, the
      suppression of postprandial lipidemia is valuable for disease management.
      Peroxisome proliferator-activated receptor- (PPAR ) is a key regulator in the
      lipid metabolism of peripheral tissues such as the liver and skeletal muscle,
      whose activation enhances fatty acid oxidation and decreases circulating lipid
      level. Recently, we have shown that bezafibrate, an agonistic compound for PPAR ,
      suppresses post-prandial lipidemia by enhancing fatty acid oxidation in
      intestinal epithelial cells under physiological conditions. However, it was not
      elucidated whether the effect of PPAR on postprandial lipidemia is also observed
      under obese conditions, which change lipid metabolisms in various tissues and
      cells. Here, we observed that bezafibrate enhanced fatty acid oxidation in
      intestinal epithelial cells of obese diabetic KK-Ay mice. Bezafibrate treatment
      increased the mRNA expression levels of fatty acid oxidation-related genes, which
      are targets of PPAR , and enhanced CO2 production from [14C]-palmitic acid. The
      bezafibrate-treated mice showed the suppression of increasing serum
      triacylglyceride level after the oral administration of olive oil. Moreover, the
      effects of bezafibrate on mRNA expression and fatty acid oxidation were shown in
      only the proximal intestinal epithelial cells. These findings indicate that PPAR
      activation suppresses postprandial lipidemia under obese conditions through the
      enhancement of fatty acid oxidation, and that only the proximal intestine con
      tributes to the effects in mice, suggesting that intestinal PPAR can be a target
      for prevention of obese-induced postprandial lipidemia.

PMID- 24455765
TI  - Dendritic cells in asthma.
AB  - The lungs are constantly exposed to antigens, most of which are non-pathogenic
      and do not require the induction of an immune response. Dendritic cells (DCs) are
      situated at the basolateral site of the lungs and continuously scan the
      environment to detect the presence of pathogens and subsequently initiate an
      immune response. They are a heterogeneous population of antigen-presenting cells
      that exert specific functions. Compelling evidence is now provided that DCs are
      both sufficient and necessary to induce allergic responses against several
      inhaled harmless allergens. How various DC subsets exactly contribute to the
      induction of allergic asthma is currently a subject of intense investigation. We
      here review the current progress in this field.

PMID- 24455768
TI  - Will our civilisation survive this century?

PMID- 24455766
TI  - The impact of viral genotype on pathogenesis and disease severity: respiratory
      syncytial virus and human rhinoviruses.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      infection (LRI) and viral death in infants. RSV disease in infants is
      characterized by epithelial desquamation, neutrophilic bronchiolitis and
      pneumonia and obstructive pulmonary mucus. Human rhinoviruses (HRVs) are by far
      the most common cause of symptomatic upper respiratory tract infection (URI) in
      people and are more recently appreciated as a significant cause of LRI. RSV and
      HRV are also implicated in asthma pathogenesis. Within both RSV and HRV, viral
      genetic differences play a role in disease severity and/or prevalence in patient
      populations, and viral genetic differences affect pathogenesis. Here, we review
      data on how viral genetic differences impact disease using RSV and HRV as
      examples, including effects on the host immune response. Virus genotype-phenotype
      relationships can be exploited in the laboratory to gain insight into mechanisms
      by which respiratory viruses modulate host immune responses and cause disease.

PMID- 24455767
TI  - Spontaneous activation of RNA-sensing pathways in autoimmune disease.
AB  - Multiple intracellular RNA sensing innate immune pathways have been linked to
      autoimmune disease. RNA-related ligands taken up by the endocytic pathway
      activate TLRs, and affect primarily immune cells. This type of activation is
      enhanced by nucleic acid-specific antibodies and induces an inflammatory program.
      In contrast, spontaneous activation of cytoplasmic RNA sensing pathways targets
      mostly non-hematopoietic tissues and their effect on autoimmune disease is
      secondary to the release of interferon in the circulation. The fact that
      pathologies result from spontaneous activation of innate pathways implies that
      endogenous RNA ligands that might be sensed as pathogenic are commonly found in
      both immune and non-immune cells.

PMID- 24455769
TI  - An arctic refugium under assault.

PMID- 24455770
TI  - Alistair Hetherington.

PMID- 24455771
TI  - Whole genome amplification of the obligate intracellular pathogen Coxiella
      burnetii using multiple displacement amplification.
AB  - This study demonstrates that whole genome multiple displacement amplification
      (MDA) is a promising technique for downstream genomic analysis of fastidious
      obligate intracellular pathogens such as Coxiella burnetii. The MDA technology
      can help in obtaining sufficient genetic material from highly infectious agent
      and thus minimizing repeated culturing and associated biohazard.

PMID- 24455772
TI  - Comparison of Neisseria gonorrhoeae MICs obtained by Etest and agar dilution for
      ceftriaxone, cefpodoxime, cefixime and azithromycin.
AB  - We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs)
      relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO)
      and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for
      cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted
      in higher CRO MICs.

PMID- 24455773
TI  - Pharmacokinetics of Cryptelytrops purpureomaculatus (mangrove pit  viper) venom
      following intravenous and intramuscular injections  in rabbits.
AB  - The pharmacokinetic profiles of Cryptelytrops purpureomaculatus (mangrove pit
      viper) venom following intravenous and intramuscular injections were investigated
      in rabbits. The serum levels of the venom were estimated using double-sandwich
      enzyme-linked immunosorbent assay (ELISA). After intravenous injection (0.2
      mg/kg), the serum venom concentration-time course declined in a biexponential
      manner, consistent with a two-compartment model, with an alpha-phase half-life of
      0.25 h and a beta-phase half-life of 27.7 h. The volume of distribution by area
      was 2.19 L/kg and systemic clearance was 54.7 mL/h/kg. When the venom was
      injected intramuscularly (0.5 mg/kg), the serum level increased rapidly to reach
      a peak (500 ng/mL) at about 1 h, which then declined rapidly to a plateau (104
      142 ng/mL) at 3-10 h before further gradual decline until the end of the 72-hour
      study. The terminal half-life (27.0 h), clearance (54.7 mL/h/kg) and volume of
      distribution (2.13 L/kg) of the venom for intramuscular route were not
      significantly different from the corresponding values for intravenous route, and
      the intramuscular bioavailability of the venom was estimated to be 41.6%.

PMID- 24455774
TI  - Scopoletin suppresses IL-6 production from fibroblast-like  synoviocytes  of
      adjuvant arthritis rats induced by IL-1beta stimulation.
AB  - Scopoletin, a coumarin compound naturally occurring in many medicinal plants, has
      previously been demonstrated to ameliorate synovial inflammation and destruction
      of cartilage and bone in adjuvant arthritis (AA) rats. As interleukin (IL)-6 is
      critically involved in the initiation and development of rheumatoid arthritis
      (RA), the present study was performed to investigate the effect of scopoletin on
      IL-6 production from fibroblast-like synoviocytes (FLS) to get insight into its
      anti-RA mechanisms. FLS were isolated from synovial membrane tissues of AA rats,
      and stimulated with IL-1beta (10 ng/mL). Scopoletin, at concentrations of 15, 30,
      and 60 MUM, was shown to only moderately inhibit FLS proliferation, but
      dramatically reduce IL-6 production at both mRNA and protein levels. It also
      inhibited the phosphorylation of p38 mitogen-activated protein kinase,
      extracellular signal-regulated kinase (ERK), protein kinase C (PKC) and cAMP
      response element binding protein (CREB). These findings suggest that scopoletin
      exerts anti-RA action probably through suppressing IL-6 production from FLS via
      MAPK/PKC/CREB pathways.

PMID- 24455775
TI  - Administration of mycobacterial Ag85A and IL-17A fusion protein  attenuates
      airway inflammation in a murine model of asthma.
AB  - Interleukin (IL)-17A contributes to the development of asthma, especially in
      severe asthma which has characteristic neutrophil infiltration in airways.
      However, IL-17A-blocking antibody could escalate T helper (Th) 2 cytokines, such
      as IL-13, IL-4 in murine models. We aimed at determining the effect of
      mycobacterial Ag85A and IL-17A fusion protein-Ag85A-IL-17A on airway inflammation
      in a murine model of asthma. IL-17A recombinant protein fused mycobacterial
      immunodominant antigen Ag85A was constructed, expressed and purified. The fusion
      protein was then administrated into BALB/c mice and its anti-inflammatory effects
      in the infiltration of inflammatory cells, Th2/Th17 cytokines in BALF,
      histopathological changes of lung tissues as well as chemokines in lung tissues
      were evaluated in the murine model of asthma. We found that administration of
      mycobacterial Ag85A and IL-17A fusion protein induced IL-17A specific
      immunoglobulin (Ig)G in sera and significantly decreased IL-17A and IL-6 levels
      in bronchoalveolar lavage fluid (BALF). Ag85A-IL-17A vaccinated mice also showed
      marked reduction in the infiltration of inflammatory cells in peribronchiolar
      region and significant decrease in total cells, eosinophil cells and neutrophil
      cells in BALF. The increased levels of IL-13 and IL-4 in BALF of ovalbumin
      sensitized mice were significantly reduced by the administration of Ag85A-IL-17A.
      Furthermore, CD3+CD4+IL-13+ splenocytes stimulated with OVA and CXCL1 mRNA, CCL2
      mRNA and GATA-3 mRNA expressed in lung tissues were decreased markedly in Ag85A
      IL-17A vaccinated group. Our results demonstrate remarkable antiallergic effects
      of Ag85A-IL-17A in a murine model of asthma and it may have protective effects on
      allergic asthma.

PMID- 24455776
TI  - Low dose naltrexone (LDN) enhances maturation of bone marrow  dendritic cells
      (BMDCs).
AB  - It has been demonstrated previously that immune cell activation and proliferation
      were sensitive to the effects of naltrexone, a non-peptidic delta-opioid receptor
      selective antagonist and opioid receptors on BMDCs have been detected [1].
      However, there is little prior data published on naltrexone and DCs. Therefore,
      we hypothesized that LDN could exert modulating effect on BMDCs. In present
      study, we studied influence of LDN on both phenotypic and functional maturation
      of BMDCs. Changes of BMDC post-treatment with LDN were evaluated using
      conventional light microscope and transmission electron microscopy (TEM); flow
      cytometry(FCM); cytochemistry; acid phosphatase activity(ACP) test; FITC-dextran
      bio-assay; mixed lymphocytes and enzyme-linked immunosorbent assay (ELISA). We
      have found that LDN enhances maturation of BMDCs as evidenced by 1) up-regulating
      the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down
      regulating the rates of pinocytosis and phagocytosis accompanied by the results
      of decreased ACP, and FITC-dextran bio-assay; 3) mounting potential of BMDCs to
      drive T cell; and 4) inducing secretion of higher levels of IL-12 and TNF-alpha.
      It is therefore concluded that LDN can efficiently promote the maturation of
      BMDCs via precise modulation inside and outside BMDCs. Our study has provided
      meaningful mode of action on the role of LDN in immunoregulation, and rationale
      on future application of LDN for enhancing host immunity in cancer therapy and
      potent use in the design of DC-based vaccines for a number of diseases.

PMID- 24455777
TI  - Ginsenoside-Rd exhibits anti-inflammatory activities through elevation  of
      antioxidant enzyme activities and inhibition of JNK and ERK  activation  in vivo.
AB  - Our previous study has reported that ginsenoside-Rd significantly inhibited the
      production of pro-inflammatory cytokines and mediators in carrageenan (Carr)
      induced rat paw edema, which might be due to its blocking of the nuclear factor
      kappaB (NF-kappaB) signaling pathway. The aim of the present study was to clarify
      the more detailed mechanisms of anti-inflammatory activity of ginsenoside-Rd in
      Carr-induced rat paw edema model. Rats were pretreated with dexamethasone or
      ginsenoside-Rd 1 h before the Carr injection. Six hours after Carr injection, the
      malondialdehyde (MDA) level and myeloperoxidase (MPO), superoxide dismutase
      (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities in inflamed paw
      tissues were determined. The levels of nitric oxide (NO) and prostaglandin E2
      (PGE2) in serum were measured. The expressions of inducible nitric oxide synthase
      (iNOS), cyclooxygenase-2 (COX-2) and NF-kappaB were detected by western blot. In
      addition, the extent of phosphorylation of extracellular signal-regulated protein
      kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK) was analyzed by western
      blot. The results showed that ginsenoside-Rd significantly attenuated MPO
      activity and MDA level, increased the activities of SOD, GPx and CAT, lowered the
      levels of NO and PGE2, down-regulated the expressions of iNOS, COX-2 and NF
      kappaB, and suppressed the phosphorylation of ERK and JNK. Taken together, the
      possible mechanisms of anti-inflammatory activity of ginsenoside-Rd were: it
      could reduce the inflammatory cell infiltration into inflammatory sites, inhibit
      the tissue lipid peroxidation, increase the antioxidant enzyme activities, and
      suppress the proinflammatory enzyme expressions through the downregulation of NF
      kappaB activation via suppression of ERK and JNK phosphorylation.

PMID- 24455778
TI  - Simultaneous presentation of plasma cell  myeloma and acute promyelocytic
      leukemia.

PMID- 24455779
TI  - Very unusual presentation of pernicious anemia with schistocytes in peripheral
      blood.

PMID- 24455780
TI  - Cell and matrix morphology in articular cartilage from adult human knee and ankle
      joints suggests depth-associated adaptations to biomechanical and anatomical
      roles.
AB  - OBJECTIVE: Marked differences exist between human knee and ankle joints regarding
      risks and progression of osteoarthritis (OA). Pathomechanisms of degenerative
      joint disease may therefore differ in these joints, due to differences in tissue
      structure and function. Focusing on structural issues, which are design goals for
      tissue engineering, we compared cell and matrix morphologies in different
      anatomical sites of adult human knee and ankle joints. METHODS: Osteochondral
      explants were acquired from knee and ankle joints of deceased persons aged 20-40
      years and analyzed for cell, matrix and tissue morphology using confocal and
      electron microscopy (EM) and unbiased stereological methods. Morphological
      variations disclosing an association between joint type (knee vs ankle) and
      biomechanical role (convex vs concave articular surfaces) were identified by a 2
      way analysis of variance (ANOVA) and a post-hoc analysis. RESULTS: Knee cartilage
      exhibited higher cell densities in the superficial zone than ankle cartilage. In
      the transitional zone, higher cell densities were observed in association with
      convex vs concave articular surfaces, without significant differences between
      knee and ankle cartilage. Highly uniform cell and matrix morphologies were
      evident throughout the radial zone in the knee and ankle, regardless of tissue
      biomechanical role. Throughout the knee and ankle cartilage sampled, chondron
      density was remarkably constant at approximately 4.2 * 10(6) chondrons/cm(3).
      CONCLUSION: Variation in cartilage cell and matrix morphologies with changing
      joint and biomechanical environments suggests that tissue structural adaptations
      are performed primarily by the superficial and transitional zones. Data may aid
      the development of site-specific cartilage tissue engineering, and help to
      identify conditions where OA is likely to occur.

PMID- 24455781
TI  - IWWG task group on landfill aeration activities during Sardinia 2013 Symposium by
      Macro Rizkowski.

PMID- 24455782
TI  - Self-change among Spanish speakers with alcohol and drug use disorders in Spain
      and the United States.
AB  - OBJECTIVE: Few cross-cultural studies have investigated the self-change process
      with substance abusers. This study examined commonalities and differences related
      to the self-change process with Spanish speaking self-changers in Spain and the
      United States (U.S.) who reported recovering from an alcohol or drug problem on
      their own (i.e., without formal help or treatment) for >=1 year. METHOD:
      Advertisements were primarily used to recruit participants. There were 56
      participants in the final sample (Spain, n=29; US; n=27). Participants provided
      demographic and substance use history information and completed the Drug Use
      History Questionnaire, Reasons for Change Scale, the Life Events Checklist, and a
      checklist for maintenance factors after recovery. RESULTS: Significantly more
      self-changers from the U.S. met DSM IV-TR criteria for alcohol dependence,
      reported significantly more life events in the year prior to recovery and
      significantly more maintenance/support events in the year after their recovery
      than their counterparts in Spain. The majority of participants' recoveries
      involved abstinence. Some alcohol abusers, however, report successfully engaging
      in low-risk drinking with no consequences(50% Spain; 22% U.S.), and some drug
      abusers in Spain (23%) reported a few days per year of very little drug use.
      CONCLUSIONS: The two groups of Spanish speakers represented very different
      cultures, and those from the U.S. came from several countries in the Southern
      hemisphere. The results of this study suggest that even though people speak the
      same language that does not mitigate against cultural differences. Additional
      studies of the process of self change with larger participant samples are needed
      to better inform the development and provision of interventions for Spanish
      speakers with alcohol and drug use disorders across different cultures and
      countries.

PMID- 24455783
TI  - Prevalence of cocaine use in Brazil: data from the II Brazilian national alcohol
      and drugs survey (BNADS).
AB  - OBJECTIVE: To determine the current prevalence rates of cocaine use and
      dependence in a representative sample of the Brazilian population, and to
      investigate possible associations with sociodemographic factors. METHOD: The
      Second Brazilian Alcohol and Drugs Survey (II BNADS) interviewed 4607 individuals
      aged 14 years and older from the Brazilian household population including an over
      sample of 1157 adolescents (14 to 18 years old).The survey gathered information
      on alcohol, tobacco and illegal substances use as well as on risk factors for
      abuse and dependence. The Severity of Dependence Scale was used to evaluate
      cocaine dependence rates among users. RESULTS: Last year consumption of crack
      cocaine was 2.2% in the overall population excluding the elderly group.Lifetime
      and last year prevalence rate of snorted cocaine was 3.9% and 1.7%, respectively.
      Smoked cocaine use in Brazil was estimated in 1.5% for lifetime and 0.8% for last
      year use. Cocaine addiction was identified in 41.4%between users in the prior
      year. CONCLUSIONS: The prevalence rates of snorted and smoked cocaine in Brazil
      suggests that the country is amongst the nations with greatest annual consumption
      rates becoming one of the biggest consumer markets of cocaine worldwide.
      Prevention and treatment policies should take this into consideration and
      strengthen the focus on cocaine use in the country.

PMID- 24455785
TI  - Hospitals facing big divide in pro- and anti-ACA states.

PMID- 24455784
TI  - Prevalence of marijuana use at college entry and risk factors for initiation
      during freshman year.
AB  - BACKGROUND: Marijuana is currently the most commonly used drug on college
      campuses. Marijuana use among college students is increasing, and many students
      begin using marijuana during college. The goal of this study was to investigate
      predictors of lifetime marijuana use at college entry and initiation during
      freshman year. METHODS: We used responses from the first two semesters of a
      longitudinal study of 3146 students from 11 colleges in North Carolina and
      Virginia. Random-effects logistic regression models were constructed to identify
      factors that predict lifetime marijuana use at college entry and initiation
      during freshman year. RESULTS: Nearly 30% of students reported ever having used
      marijuana at college entry. Among students who had never used marijuana prior to
      college, 8.5% initiated use during freshman year. In multivariable logistic
      regression models, having at least $100 per month in spending money; attending
      church rarely or never; current use of cigarettes, alcohol, and hookah tobacco;
      lifetime use of other illicit drugs; and a higher propensity toward sensation
      seeking were associated with a higher likelihood of having used marijuana at
      least once at college entry. Hispanic ethnicity, living on campus, and current
      use of cigarettes and alcohol were associated with a higher likelihood of
      initiating marijuana use during freshman year. CONCLUSION: These results have
      implications for targeting substance abuse prevention programs on college
      campuses.

PMID- 24455790
TI  - [Abstracts of the 2nd Pulmonary Hypertension Workshop. February 2011. Leverkusen,
      Germany].

PMID- 24455791
TI  - Abstracts of the Society of Critical Care Medicine 41st Critical Care Congress.
      February 4-8, 2012. Houston, Texas, USA.

PMID- 24455792
TI  - Medical devices; immunology and microbiology devices; classification of John
      Cunningham Virus serological reagents. Final order.
AB  - The Food and Drug Administration (FDA) is classifying John Cunningham Virus (JCV)
      serological reagents into class II (special controls). The Agency is classifying
      the device into class II (special controls) in order to provide a reasonable
      assurance of safety and effectiveness of the device.

PMID- 24455793
TI  - [Abstracts of Dermatology Days. December 2012. Paris, France].

PMID- 24455794
TI  - Management of myelodysplastic syndromes in adults: guidelines from the Belgian
      Haematological Society.
AB  - Myelodysplastic syndromes (MDS) represent a heterogeneous group of haematological
      disorders characterized by ineffective haematopoiesis and an increased risk for
      leukemic transformation. In recent years several new therapeutics have emerged
      that have demonstrated to alter the natural course of the disease. This document
      summarizes the state of the art in diagnosis and treatment of this heterogeneous
      disease, as proposed by a group of expert haematologists in the field of MDS from
      the Belgian Haematological Society. Its main purpose is to guide clinicians in
      daily practice to treat patients with this disease, within the limitations of
      current reimbursement modalities in Belgium.

PMID- 24455795
TI  - Costs associated with readmissions in Belgian acute-care hospitals.
AB  - INTRODUCTION: Internationally, hospital readmissions have a great appeal as an
      indicator of hospital quality. Since possibilities in prevention and control
      exist, reducing rates of hospital readmission has attracted attention of
      policymakers as a way to improve quality of care while simultaneously reducing
      costs. Therefore reducing the number of readmissions is considered to be a pillar
      of more cost-effective hospital care. The goal of this study was to estimate the
      cost of hospital readmissions at a national level, describe differences in
      readmission rates between hospitals and to calculate the potential monetary
      savings of reducing excess readmissions. METHODS: Stays data were obtained from
      the Minimum Basic Data Set 2008 in a sample of 45 hospitals representing 16,141
      beds. Readmissions were identified as a second admission for the same patient
      with the same APR-DRG code within 1 month or 3 months after discharge. Hospital
      type, diagnosis-related group, age and gender were used as matching factors in
      comparing readmission rates. Specific types of readmissions that occur naturally
      in each other's proximity due to the repeating nature of the therapy were
      excluded from the analysis. The costs per readmission were then calculated by
      linking the stays data with the cost data per APR-DRG and per severity index
      using the 2008 national feedback. The results of our sample were then
      extrapolated to all Belgian hospitals in order to calculate the total cost of
      readmissions. By means of a sensitivity analysis we estimated potential monetary
      savings when a reduction in the incidence of readmissions in hospitals having a
      higher readmission rate in comparison to other hospitals would be realized.
      RESULTS: In our sample 1.5% readmissions within 1 month after discharge and 2.1%
      within 3 months after discharge were identified. The additional weighted mean
      cost of these readmissions was Euro 3,495.58 within 1 month and Euro 3,572.20
      within 3 months. The total financial burden, as extrapolated to the Belgian
      setting, is estimated at Euro 280,091,471.The wide variability between hospitals
      in incidence of readmissions (1.17-6.40%) indicates a potential for improvement.
      For instance, if all Belgian hospitals having a higher readmission rate improve
      their rate to the level of the hospital corresponding to percentile 75 (= 2.4%
      readmissions) savings would amount to Euro 14,118,509. CONCLUSION: The observed
      incidence of readmissions is associated with important additional healthcare
      costs. Although not all readmissions can be prevented, there is clearly a
      potential to increase cost-effectiveness of hosp tal care delivery.

PMID- 24455796
TI  - Update on idiopathic hirsutism: diagnosis and treatment.
AB  - Idiopathic hirsutism (IH) is defined as hirsutism in conjunction with normal
      ovulatory function and normal serum androgen levels. The pathogenesis of IH is
      still not clear. Increased peripheral 5alpha-reductase enzyme activity and
      abnormalities of androgen receptor gene polymorphisms have been postulated to
      explain the pathogenesis of this disorder. It is diagnosed in women who have
      hirsutism, normal ovulatory function, and normal levels of serum total or free
      testosterone. Combination treatment of IH, including androgen suppression,
      peripheral androgen blockade and cosmetic methods is most effective.

PMID- 24455797
TI  - Cinacalcet for managing secondary hyperparathyroidism in dialysis patients in
      clinical practice in Belgium: a 16-month observational study (ECHO-B).
AB  - In Belgium, the calcimimetic cinacalcet is initially reimbursed for < or = 4
      months in dialysis patients with secondary hyperparathyroidism (SHPT) and intact
      parathyroid hormone (iPTH) > or = 800 pg/mL, or iPTH 300-800 pg/ mL and Ca x P >
      55 mg 2/dL2 despite > or = 6 months' optimal treatment with vitamin D sterols
      and/or phosphate binders. The Belgian, multicentre, observational study ECHO-B
      evaluated cinacalcet in such patients. Patients who began cinacalcet treatment
      after March 1, 2007 were eligible. Data were collected retro/prospectively from 6
      months before until 16 months after starting cinacalcet (whether or not
      cinacalcet was continued). Median iPTH was markedly elevated (816 [IQR 551-991]
      pg/mL) at baseline (the time of starting cinacalcet), but decreased continuously
      over the course of the study, reaching a value of 414 pg/mL (IQR 240-641; median
      change -41%) at 4 months, 335 pg/mL (IQR 159-616; -60%) at 12 months and 250
      pg/mL (IQR 172-436; -64%) at 16 months. Reductions in serum calcium (-7%) and
      phosphorus (-13%) were already (near) maximal at 4 months. The primary outcome
      (iPTH 150-300 pg/mL and/or a > or = 30% reduction within 4 months of starting
      cinacalcet; criterion for continued reimbursement in Belgium) was achieved in
      65/81 patients (80%; 95% CI 72-89%). Results show that in dialysis patients with
      SHPT in real-life clinical practice, mineral metabolism improves after starting
      cinacalcet: our study findings suggest that PTH levels may continue decreasing
      after 12 months' treatment in this setting.

PMID- 24455798
TI  - Interpretation of hemolysis tests following administration of a second-generation
      hemoglobin-based oxygen carrier.
AB  - Hemoglobin released into the circulation during hemolysis or therapy with
      chemically modified hemoglobins, exert oxidative and NO-scavenging toxic effects.
      Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) is one of the second
      generation hemoglobin-based oxygen carriers (HBOCs). We wanted to investigate the
      metabolism of PHP with a special focus on its consequences for interpreting
      hemolysis-related diagnostic parameters in PHP-treated patients. Clinical samples
      were analyzed from 3 patients, who received PHP (as part of the PHOENIX phase III
      trial) for treatment of catecholamine-resistant distributive shock. In contrast
      to expectations, clearance of PHP by hemopexin, instead of haptoglobin was
      documented by increased hemolysis indices, absence of decreased haptoglobin
      values, presence of free PHP-hemoglobin and exhausted hemopexin concentrations.
      The present case report is important for both clinicians and laboratorians since
      it nicely illustrates that a hemolytic aspect of plasma is not necessarely
      synonymous with hemolysis. A hemolytic aspect of plasma or serum (high hemolysis
      index) in combination with normal or increased haptoglobin values should draw the
      attention; additional determination of lactate dehydrogenase and hemopexin may
      then be useful to distinguish the condition from in vitro hemolysis and to
      monitor the in vivo elimination of the heme compounds.

PMID- 24455799
TI  - SGLT2-inhibitors: a novel class for the treatment of type 2 diabetes introduction
      of SGLT2-inhibitors in clinical practice.
AB  - Treatment of type 2 diabetes (T2DM) continues to present challenges, with
      significant proportion of patients failing to achieve and maintain glycemic
      targets. Despite the availability of many oral antidiabetic agents, therapeutic
      efficacy is offset by side effects such as weight gain and hypoglycemia.
      Therefore, the search for novel therapeutic agents with an improved benefit-risk
      profile continues. Recent research has focused on the kidney as a potential
      therapeutic target, especially because maximal renal glucose reabsorption is
      increased in T2DM. Under normal physiological conditions, nearly all filtered
      glucose is reabsorbed in the proximal tubule of the nephron, principally via the
      sodium-glucose cotransporter 2 (SGLT2). SGLT2-inhibitors are a new class of oral
      antidiabetics, which reduce hyperglycemia by increasing urinary glucose excretion
      independently of insulin secretion or action. Clinical results are promising with
      significant lowering of HbA1c without increased risk of hypoglycemia, reduction
      of body weight and reduction of systolic blood pressure. Dapagliflozin is the
      first highly selective SGLT2-inhibitor approved by the European Medecine Agency.
      Canagliflozin and empagliflozin are undergoing phase III trials. Actual safety
      issues are an increased risk for genital- and urinary tract infections and a
      possible increased risk for bladder and breast cancer. This led to refusal of
      dapagliflozin by the Food and Drug Administration (FDA). A large randomized
      control trial is therefore warranted by the FDA. This review provides an overview
      of the current evidence available so far on the therapeutic potential of the
      SGLT2-inhibitors for the treatment of T2DM.

PMID- 24455800
TI  - The immune reconstitution inflammatory syndrome: a cause of death in persons on
      antiretroviral therapy?
AB  - The availability of antiretroviral therapy (ART) has significantly improved the
      quality of life of persons with HIV infection. However, new problems have arisen
      as a consequence of this treatment. An immune reconstitution inflammatory
      syndrome (IRIS) in which patients experience a paradoxical worsening of their
      clinical condition may occur during recovery of the immunity. Thus far, there is
      no laboratory test available to diagnose IRIS. The diagnosis therefore remains
      clinical and by exclusion. In this paper, we describe the autopsy findings of
      three HIV-infected patients who died at the Antwerp University hospital directly
      or indirectly related to IRIS. One patient died following a disseminated
      cryptococcocal and Mycobacterium avium complex (MAC) infection. Two other
      patients died with a disseminated aspergillosis infection after receiving
      corticosteroids to decrease IRIS induced inflammatory signs. These three patients
      show the difficulties faced by clinicians in diagnosing IRIS and the importance
      of performing autopsies in persons with HIV infection who die despite receiving
      ART.

PMID- 24455801
TI  - D-dimer cut-off adjusted to age performs better for exclusion of pulmonary
      embolism in patients over 75 years.
AB  - INTRODUCTION: A D-dimer (DD) test improves the diagnosis of PE (PE) when combined
      with clinical scores. However, as DD levels increase physiologically with age,
      this testing has less specificity in older patients. Douma et al. (1). proposed
      the use of an age adjusted DD cut-off to increase the specificity of this test.
      METHODS: We performed chart reviews of patients, older than 75 years,
      hospitalized for suspicion of PE in 2010-2011 (n = 165). PE was assessed with
      either pulmonary scintigraphy (PS, n = 64) and/or pulmonary computed tomography
      (PC, n = 101). We compared the specificity, sensitivity and false negatives rates
      of an age adjusted DD cut-off level ("ADC" = (patient's age x 0.01) microg/ml)
      with those of the conventional cut off level ("CDC" = 0.5 microg/ml). RESULTS: PE
      was confirmed in 45 cases. In the 120 patients with no PE (negative PS or PC), 7
      cases had CDC below cut-off levels, while 28 cases had an ADC below cutoff level.
      The use of the ADC thus increased the specificity (ADC: 23% vs CDC: 6%, p =
      0.0001), and this was obtained without significant loss of sensitivity (ADC: 96%
      vs CDC: 98%, ns). Patients were clinically assessed with the revised Geneva
      scores. In the negative PE group, the number of patients classified with low,
      moderate or high clinical probability of PE were 31, 81 and 8, respectively. The
      percentage of patients with DD values below cut-off values was 4%, 0.8% and 0.8%,
      respectively using the CDC and 9%, 12% and 2.5% using the ADC. CONCLUSIONS: In
      this age group, the specificity of ADC was found superior to that of the CDC. The
      clinical use of the ADC might be associated with less useless diagnosis
      procedures, without significant increase in rate of diagnosis failure.

PMID- 24455802
TI  - Unexplained cardiac failure leading to the identification of a Belgian family
      affected by hereditary amyloidosis.
AB  - We report the diagnosis of hereditary amyloidosis that affected a Belgian family
      that was initially diagnosed in a 73 year old woman. This patient was admitted
      with complaints of congestive heart failure. Cardiac work-up showed myocardial
      hypertrophy with zones of hyperintensity, suggestive for amyloidosis that was
      confirmed on a rectal biopsy. A hereditary form of amyloidosis was found by
      showing the Val30Met mutation within the transthyretin gene, that was also found
      in her asymptomatic son. This case shows that genetic testing is crucial in cases
      of unexplained amyloidosis and can help in the diagnosis and follow-up of
      patients and family members.

PMID- 24455803
TI  - A rare complication after pulmonary function test: spontaneous pneumomediastinum,
      pneumopericardium and subcutaneous emphysema.

PMID- 24455804
TI  - Acute pancreatitis induced by anticancer chemotherapy.
AB  - Drug-induced pancreatitis is rare (1.4-2%). This report describes a 20-year-old
      female patient who developed acute pancreatitis while being treated for
      neurosarcoma of abdominal wall with the ifosfamide and doxorubicin regimen.
      Although it is unusual, it is important to consider chemotherapeutic agents as a
      possible etiology for acute pancreatitis in patients presenting with
      gastrointestinal symptoms.

PMID- 24455806
TI  - Special section: applications of research in cognitive psychology to training in
      the real world.

PMID- 24455805
TI  - Diaphragm plication for unilateral diaphragm paralysis: a case report and review
      of the literature.
AB  - Unilateral diaphragm paralysis is an often not recognised cause of dyspnoea. We
      present a patient with a unilateral phrenic nerve paralysis treated with
      diaphragmatic plication. Patient presented with life-style limiting dyspnoea and
      pulmonary function showed a decrease in FVC when lying down. Since there was no
      improvement after respiratory muscle training, plication of the hemidiaphragm was
      performed by a small thoracotomy. The patient improved with regard to respiratory
      complaints and lung function. Furthermore, we also demonstrate for the first time
      a significant improvement in exercise capacity with accompanying striking
      amelioration of quality of life. The patient is now in follow up up for more than
      2 years and the impressive improvement in exercise capacity remains present.
      Surgical treatment of unilateral diaphragm paralysis has been described in case
      reports and in small series since 1985. Although comparison of the available data
      is difficult a diaphragm plication seems an effective and safe procedure for
      patients with symptomatic, acquired unilateral diaphragm paralysis. Improvement
      of dyspnoea is present in the majority of patients and we even observed an
      impressive amelioration in exercise capacity. Consequently, it seems appropriate
      to propose plication to patients with clear symptoms from the moment spontaneous
      recovery seems unlikely; yet, prospective randomised controlled studies are
      needed to prove this.

PMID- 24455807
TI  - Empirically valid principles for training in the real world.
AB  - Four sets of cognitive psychology experiments are aimed to identify and
      empirically support principles of training intended to increase training
      effectiveness. Each set supports a different training principle: strategic use of
      knowledge (learning and memory are facilitated whenever preexisting knowledge can
      be used as a mediator in the process of acquisition), training difficulty
      (conditions that cause desirable difficulties during learning might facilitate
      later retention and transfer), mental practice (mental practice can retard
      forgetting and promote transfer of training, sometimes to a larger extent than
      can physical practice), and cognitive antidote (adverse effects of prolonged work
      on routine tasks can be mitigated by adding cognitive complications). The first 2
      principles are focused on knowledge acquisition and the last 2 on skill
      acquisition. Nevertheless, the principles converge on similar prescriptions:
      Contrary to intuition and common practice, the trainer is recommended to increase
      the complexity of the training situation rather than use the simplest methods
      available.

PMID- 24455808
TI  - Specificity of transfer in basic and applied perceptual-motor tasks.
AB  - We conducted research on transfer of skills using basic stimulus-response
      compatibility tasks and applied tasks requiring control of a hydraulic excavator
      simulator. The basic tasks show rapid acquisition of practiced spatial mappings,
      for which transfer is specific to the procedures used in training. The applied
      tasks show transfer across alternative control configurations that maintain
      practiced spatial mappings, as well as from part to whole practice. Transfer from
      simulated to real equipment also seems to occur; however, studies involving
      cooperation of academia and industry are needed to provide more definitive
      evidence on this question.

PMID- 24455809
TI  - Part-task training in the context of automation: current and future directions.
AB  - Automation often elicits a divide-and-conquer outlook. By definition, automation
      has been suggested to assume control over a part or whole task that was
      previously performed by a human (Parasuraman & Riley, 1997). When such notions of
      automation are taken as grounds for training, they readily invoke a part-task
      training (PTT) approach. This article outlines broad functions of automation as a
      source of PTT and reviews the PTT literature, focusing on the potential benefits
      and costs related to using automation as a mechanism for PTT. The article reviews
      some past work in this area and suggests a path to move beyond the type of work
      captured by the "automation as PTT" framework. An illustrative experiment shows
      how automation in training and PTT are actually separable issues. PTT with
      automation has some utility but ultimately remains an unsatisfactory framework
      for the future broad potential of automation during training, and we suggest that
      a new conceptualization is needed.

PMID- 24455810
TI  - Application of part-whole training methods to evaluate when to introduce NextGen
      air traffic management tools to students.
AB  - The Next Generation Air Transportation System (NextGen) will use advanced
      technologies and new concepts of operation to accommodate projected increases in
      air travel over the next few decades. Use of NextGen tools requires air traffic
      controllers (ATCos) to use different procedures than those required to manage
      NextGen-unequipped aircraft, and ATCos will need to integrate the 2 skill sets
      when managing a sector consisting of NextGen-equipped and unequipped aircraft.
      The goal of the present study was to determine the effectiveness of 2 procedures
      in the training of student controllers to manage both equipage types. We applied
      a variant of the part-whole training paradigm in the present study. Using a quasi
      experimental design, we trained students from 2 different labs of an internship
      course to manage air traffic with potential NextGen tools concurrent with their
      traditional training (whole-task group) or after they had time to learn
      traditional air traffic management skills (part-whole group). Participants were
      then tested in their ability to manage a simulated sector consisting of different
      percentages of NextGen-equipped and unequipped aircraft at the mid-term and after
      the final week of their internship. Results showed that it is better to train
      students in manual ATCo skills before introducing NextGen tools, unless the
      students are of higher aptitude. For more skilled students, simultaneously
      introducing NextGen and manual tools into their curriculum had little negative
      impact.

PMID- 24455811
TI  - Examining the relationship between knowing and doing: training for improving food
      choices.
AB  - Food is essential for maintaining human life; however, our food choices can have
      negative impacts on the health of our bodies and our planet. For example, obesity
      and diet-related diseases are increasing at alarming rates. In addition,
      agricultural chemicals are detectable in many rivers and streams, contaminating
      drinking water. Thus, understanding what factors contribute to food choices is
      essential for those interested in social change. This article reviews some
      principles of learning and memory and how applications of those principles
      contribute to our understanding of food choices. Experiments that examine
      different ways to promote learning, retention, and generalization of knowledge,
      specifically focused on ways to enhance learning of nutritional information and
      food choices, are also reviewed. The practical applications of this research to
      training, health, and public policy are also discussed.

PMID- 24455812
TI  - A child's garden of curses: a gender, historical, and age-related evaluation of
      the taboo lexicon.
AB  - Child swearing is a largely unexplored topic among language researchers, although
      assumptions about what children know about taboo language form the basis for
      language standards in many settings. The purpose of the studies presented here is
      to provide descriptive data about the emergence of adultlike swearing in
      children; specifically, we aim to document what words children of different ages
      know and use. Study 1 presents observational data from adults and children (ages
      1-12). Study 2 compares perceptions of the inappropriateness of taboo words
      between adults and older (ages 9-12) and younger (ages 6-8) children.
      Collectively these data indicate that by the time children enter school they have
      the rudiments of adult swearing, although children and adults differ in their
      assessments of the inappropriateness of mild taboo words. Comparisons of these
      data with estimates obtained in the 1980s allow us to comment on whether swearing
      habits are changing over the years. Child swearing data can be applied to
      contemporary social problems and academic issues.

PMID- 24455813
TI  - Relevance of Piagetian cross-cultural psychology to the humanities and social
      sciences.
AB  - Jean Piaget held views according to which there are parallels between ontogeny
      and the historical development of culture, sciences, and reason. His books are
      full of remarks and considerations about these parallels, with reference to many
      logical, physical, social, and moral phenomena.This article explains that
      Piagetian cross-cultural psychology has delivered the decisive data needed to
      extend the research interests of Piaget. These data provide a basis for
      reconstructing not only the history of sciences but also the history of religion,
      politics, morals, culture, philosophy, and social change and the emergence of
      industrial society. Thus, it is possible to develop Piagetian theory as a
      historical anthropology in order to provide a basis for the humanities and social
      sciences.

PMID- 24455814
TI  - Surgeons put planning, preparation, past experience to work in efforts to save
      Boston Marathon bombing victims.

PMID- 24455815
TI  - Active shooter and intentional mass-casualty events: the Hartford Consensus II.

PMID- 24455816
TI  - ACS transition to practice program offers residents additional opportunities to
      hone skills.

PMID- 24455817
TI  - Mandating the use of motorcycle helmets: what are the issues?

PMID- 24455818
TI  - Online physician reviews: the good, the bad and the ugly.

PMID- 24455819
TI  - The Harvard RBRVS: where is it going? 1989.

PMID- 24455820
TI  - The Medicare EHR Incentive Program deadlines.

PMID- 24455821
TI  - Update: PQRS reporting of the perioperative care measures group.

PMID- 24455822
TI  - American College of Surgeons Commission on Cancer Rapid Quality Reporting System:
      from quality measurement to quality improvement.

PMID- 24455823
TI  - NTDB data points: derailed.

PMID- 24455824
TI  - Barbara Lee Bass, MD, FACS, selected to receive 2013 Distinguished Service Award.

PMID- 24455825
TI  - In memoriam: George F. Sheldon, MD, FACS: a lifetime achievement as a scholar,
      surgical educator.

PMID- 24455826
TI  - In memoriam: John Mann Beal, MD, FACS, remembered as caring surgeon, educator,
      and advocate for the surgical profession.

PMID- 24455827
TI  - 2013 Japan Traveling Fellow reports on experience.

PMID- 24455828
TI  - [Undercarboxylated osteocalcin (Glu-OC) bone metabolism and vascular
      calcification in hemodialyzed patients].
AB  - Osteocalcin (OC) is witamino-K dependent calcium-binding protein comprising three
      gamma carboxy glutamic acid residues (Gla) which determines a strong bond with
      hydroxyapatite. In vitamin K deficiency and/or increased bone resorption
      undercarboxylated osteocalcin (Glu-OC) appears in the blood. The aim of this
      study was to evaluate the level of Glu-OC and markers of bone metabolism and
      their impact on coronary artery calcification in patients with end-stage renal
      failure treated with repeated hemodialysis. The study included 68 patients (29
      women and 39 men) aged 60.3 +/- 12.3 years hemodialysis period 24.5 +/- 4.8
      months. Control group consisted of 35 healthy volunteers comparable in terms of
      age and gender. CACS was evaluated based on multislice spiral computed tomography
      (MSCT). Measurement of carboxylated osteocalcin (Gla-OC) and Glu-OC, bone
      alkaline phosphatase (bALP), tartrate-resistant acid phosphatase (TRAP5) were
      assessed by ELISA and iPTH by Nichols method. Present study demonstrated that the
      Gla-OC and Glu-OC in hemodialysis patients were significantly higher than the
      control group 116.37 +/- 70.01 ng/ml and 93.72 +/- 112.63 ng/ml versus 19.51 +/-
      3.78 ng/ml and 4.88 +/- 2.63 ng/ ml; p <0.001. Glu-OC level correlated
      significantly with iPTH, bALP, TRAP5 (p <0.001) and CaSc (p <0.014). CONCLUSIONS:
      1. The results indicate a significant correlation between Glu-OC and assessed
      markers of bone metabolism. 2. Research has indicated a link between bone
      metabolism and the degree of calcification in the coronary arteries.

PMID- 24455829
TI  - [Early results after surgical treatment of femoral neck fractures with total
      cementless hip arthroplasty].
AB  - The aim of the study was to assess early results after the treatment of femoral
      neck fractures with the cementless hip arthroplasty as well as complications
      after the earlier fixation of these fractures in patients aged 55-70 years.
      MATERIAL AND METHODS: 40 cementless hip arthroplasty procedures with the use of
      Bicontact S endoprosthesis were performed, including 33 due to the femoral neck
      Garden III and IV type fractures, 7 due to the destabilization of the earlier
      performed bone fixation with DHS (Dynamic Hip Screw) or the nonunion after the
      fracture fixation. Postoperative complications as well as early clinical and
      radiological results were assessed. Outpatient follow-up examinations assessed
      patients using Harris Hip Score (HHS) and Visual Analogue Scale (VAS), to
      estimate their quality of life and the level of contentment. RESULTS: The total
      cementless hip arthroplasty with the use of Bicontact endoprosthesis allows to
      achieve very good early clinical results in patients who have undergone the
      surgical procedure due to the femoral neck fracture and good clinical results in
      patients who have undergone this surgery because of complications after the
      fixation of fractures. In the examined group of patients early radiological
      results were good. CONCLUSIONS: Based on the very good and good early results of
      clinical trials can be assumed that the total cementless hip arthroplasty will be
      an effective and recommended method of treatment of femoral neck fractures and
      complications after the earlier fixation of these fractures in patients aged 55
      to 70 years, but this requires further, long-term observation. Total hip
      arthroplasty, not the fixation, should be more often considered as a primary care
      management of fractures of this type because it allows for a pain-free walking
      faster and faster return to pre-injury functioning.

PMID- 24455830
TI  - [The changes in complete blood count in patients treated with sunitinib malate
      for metastatic clear cell renal cell carcinoma].
AB  - Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies.
      For stage I - III RCC surgery is the primary treatment. Systemic therapy is used
      in the patients with disseminated disease (stage IV). Sunitinib malate is
      commonly used in the patients with clear cell renal cell carcinoma (ccRCC) rated
      as 'low' or 'intermediate' risk according to the Motzer scale. Treatment with
      sunitinib malate is associated with myelotoxicity. To assess its clinical
      significance we conducted a pilot study in a group of 10 patients. We noticed a
      gradual decrease in the mean haemoglobin level during subsequent treatment
      cycles. Alternations in the platelet count were of no clinical significance.
      Episodes of the neutropenia were noticed in the study group. In some patients
      neutrophil count decreased to the level that put them at risk of the infectious
      complications.

PMID- 24455831
TI  - [Health of patients after bone marrow transplantation and coping with stress --
      psychological and medical perspective].
AB  - A study on the relationship between level of subjective and objective health by
      patients after bone marrow transplantation (BMT) and their coping with stress is
      presented. The theoretical basis of researches is Helena Wrona-Polanska's
      Functional Model of Health (2003), in which health is a function of creative
      coping with stress.141 patients after BMT -- 80 males and 61 females -- at the
      Hematology Clinic of University Hospital were studied clinically. Objective
      health was examined doctor on the scales. Examined methods were -- the
      questionnaires examining stress, coping strategies, and grading scales of health
      and anxiety. There is a clear difference between subjective and objective level
      of health. Subjective health depend on coping strategies with stress and
      objective health depend on patient's collaboration with terapeutic team. The
      basis of health promotion by persons after BMT is development effective
      strategies of coping with stress and increase patent's activity.

PMID- 24455832
TI  - [Autonomic nervous system estimation by heart rate variability analysis in
      experimental short and long-lasting bladder outlet obstruction model].
AB  - INTRODUCTION: Benign prostatic hyperplasia; BPH is associated with the symptoms
      of the bladder overactivity. This disease can be comparatively easly induced
      using an animal model of the partial bladder outlet obstruction; PBOO. The
      pathophysiological description of BPH is still incomplete, thus autonomic nervous
      system activity assessement in the course of PBOO seems to be important. MATERIAL
      AND METHODS: The experiment was carried out on 30 Wistar rats. 10 animals "sham"
      operated served as control group (group 1). Another 20 rats underwent the PBOO
      surgery. In all studied animals in urethane anaesthesia short-term (20 minutes
      lasting) heart rate variability (HRV) recordings were taken with the subse quent
      time-and spectral HRV analysis. In control rats, the HRV study was done after 7
      days of sham operation while the PBOO animals were divided into two subgroups:
      with short lasting PBOO (group 2; the HRV records were collected on the 14th the
      day since the surgery) and with long-lasting PBOO (group 3; HRV records on the
      29th day after surgery). After HRV collection, all studied animals were given a
      lethal pentobarbital dose and urinary bladders were removed for histopathological
      assessement. RESULTS: Bladders collected from PBOO rats were characterised by
      signs of congestion and edema with features of the excessve bladder wall
      muscularisation. The majority of the time-domain HRV analyzed parameters did not
      significantly differ in all studied groups. The total HRV spectrum power(TP), as
      well as the power of the low frequency component (LF) and high frequency one (HF)
      were markedly higher in the control group. In PBOO animals, the trend of the
      progressive power decrease of main HRV spectrum components was observed. The
      significant changes relating to the standardized HRV parameters were pronounced.
      In control rats, the nLF value was smaller while nHF - higher when compared to
      the group 2. Just the opposite, when combine the control and 3 group it was
      showed, that the value of nLF was higher and nHF - smaller in control animals.
      CONCLUSIONS: Our results suggest, that the partial bladder outlet obstruction
      causes both the bladder remodelling and the functional changes of the autonomic
      nervous system which become more stressed with the BOO duration. 14-days lasting
      PBOO model caused decrease of the global autonomic tension, but with the
      maintaining of the mutual relations between the main ANS branches: sympathetic
      part and parasympathetic one. The monthly PBOO period caused the more marked
      autonomic dysfunction manifesting by considerable lowering of the total autono
      mic tension and the shift of autonomic balance towards to o parasympathetic
      predominance.

PMID- 24455833
TI  - [Mycophenolate mofetil in the treatment of selected connective tissue diseases].
AB  - Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate
      dehydrogenase, which affects de novo purine synthesis and T- and B-cell
      proliferation. So far its efficacy and safety as an immunosuppressive treatment
      have been proven in organ transplantations and also in various autoimmune
      diseases. A literature search was conducted by using PubMed and the Cochrane
      library. This review focuses primarily on current treatment with MMF for systemic
      lupus erythematosus, systemic sclerosis, vasculitis and idiopathic inflammatory
      myopathies.

PMID- 24455834
TI  - [Clinical aspects of the use of trimetazidine in the prevention and treatment of
      myocardial diseases].
AB  - Trimetazidine, next to ranolazine and L-carnitine, belongs to cardioprotective
      drugs and as their main agent is used in experimental and clinical trials to
      evaluate its effect on modulation of cardiomyocytes metabolism. The blockade of
      fatty acid oxidation in ischemic myocardium and increase in the glucose
      utilization are the main mechanisms of trimetazidine action, which eventually
      lead to the reduction in intracellular acidosis. Recent studies concerning
      cardioprotective treatment encourage to continue the research on effectiveness,
      possible side effects, and clinical outcome which arise from "metabolic shift"
      toward the improvement of glucose metabolism. It has been demonstrated that
      trimetazidine not only ameliorate the quality of life by increasing physical
      tolerance, but also inhibits cardiac remodeling associated with long-standing
      diabetes or ischemia. Futhermore, trimetazidine exhibits antiarrhythmic
      properties and reduces myocardial damage associated with oxidative stress and
      inflammation after invasive procedures. In the light of these findings,
      trimetazidine seems to be an attractive therapeutic option andlor complementary
      therapy for treated conservatively patients with heart disease and with high risk
      of postreperfusal damage after cardiac invasive procedures. Moreover,
      particularly large benefits from introducing the metabolic treatment obtain
      patients with diabetes. The literature concerning trimetazidine function and
      treatment is broad. Therefore, the aim of this article is to summarize recent
      multicenter clinical trials on metabolic cardioprotection, showing its
      effectiveness or neutrality to the myocardial damaging factors.

PMID- 24455835
TI  - [Gene polymorphism of the vitamin D receptor, vitamin D-binding protein and
      calcium-sensing receptor in respect of calcium-phosphate disturbances in chronic
      dialysis patients].
AB  - Dialysed patients suffering from chronic kidney disease (CKD) show varied levels
      of concentration of parathyroid hormone (PTH) in the blood. One of the factors in
      charge of regulating levels of PTH concentration is 1,25-dihydroxycholecalciferol
      [1,25-(OH)2D3]. Its deficiency in advanced stages of CKD is common. Vitamin D
      supplementation is not always effective in reaching levels of PTH concentration
      recommended by KDIGO for the dialysed patients. That suggests, among other
      things, disturbances in 1,25-(OH)2D3, reaching its place of target effect and
      having the desired final result. Disturbances of vitamin D target pathway can be
      genetically conditioned, hence the aim of this paper is to describe the
      distribution of polymorphic variants of vitamin D-binding protein gene (VDBP),
      vitamin D receptor gene (VDR) and gene of the calcium-sensing receptor (CaSR)
      with respect to PTH concentrations in serum and response to cinacalcet treatment
      in patients with secondary hyperparathyroidism in view of the differences in
      demographical, clinical and laboratory data of the dialysed patients.

PMID- 24455836
TI  - [Transcatheter aortic valve implantation and its place in the contemporary
      treatment].
AB  - Symptomatic stenosis of the aortic valve has recently been an important clinical
      issue. On one hand the number of patients who need surgical treatment of valve
      failure is increasing. On the other hand their general state of health and
      concomitant diseases determine that they are disqualified from surgery. The
      trasncutaneus technique of replacement of the aortic valve is for these patients
      a promising alternative. Therefore TAVI procedures have been developed and the
      number of performed transcatheter aortic valve replacements is still increasing.
      Although it would appear unlikely that TAVI could replace traditional surgery in
      the nearest future, it remains a possible treatment option for some of the high
      risk patients not suitable for surgery.

PMID- 24455837
TI  - [Necessary diagnostic requirements and therapeutic recommendations in multiple
      myeloma].
AB  - Recent years have brought new diagnostic and therapeutic tools for the patients
      with multiple myeloma. New methods have become available to assess the biology
      and the extent of multiple myeloma, such as testing for cytogenetic and precise
      evaluation of extramedullar and minimal residual disease. New drugs have entered
      the clinical practice leading to significant outcome improvements but also
      resulting in the need of prevention and treatment for their side effects. In this
      review, novel diagnostic and therapeutic methods are discussed in the context of
      their practical utilization in a real-life clinical practice.

PMID- 24455838
TI  - [Unsuccessful suicidal attempt with use of self-prepared bullet -- case report].
AB  - Gunshot injuries of the viscerocranium are rarely reported during times of peace
      in Europe. Penetrating wounds to the maxillofacial region pose a significant
      challenge for surgeons as they often comprise serious soft and bone tissue
      defects.We present a case report of 38-year-old male with gunshot wound to the
      viscerocranium after suicidal attempt. The patient's general condition was
      stable. The inlet wound was found in the submental region in the central line
      penetrating deep into the floor of the mouth, to the left, avoiding large vessels
      and hypoglossal nerve. No exit wound was identified. The ophthalmic examination
      revealed the limitation of motion in the left eyeball and diplopia in the whole
      field of vision. The revision was performed under general anesthesia. Control CT
      scan revealed the presence of one metallic fragment wedged in the hard palate.
      Second look of oral cavity with particular emphasis on the hard palate was
      performed. Shrapnel proved to be wedged in the bone of the hard palate very
      firmly and complete removal without damaging the function of the palate was
      impossible. The decision was made to withdraw from surgical removal of the
      remaining piece of the projectile. In most cases, it is recommended to remove all
      foreign material from human body. However, in the illustrated case we decided to
      leave small debris in the craniofacial skeleton. In our opinion, further surgical
      revision would result in greater tissue damage, disproportionate to the benefits
      of the removal of all fragments of the projectile.

PMID- 24455839
TI  - [Local complications of lip and tongue piercing -- report of the cases].
AB  - Piercing, which is the form of puncturing parts of the human body and creating
      openings where jewelry can be worn, is together with tattoos, body drawings or
      make-up, one of the oldest way of decorating of the human body. Piercing can be
      performed in each part of the body. In the recent years face piercing (nose,
      eyebrows, lip region) and in the oral cavity (tongue, lips, cheek, mentolabial
      sulcus, labial frenulum) is becoming particularly popular. The procedure of
      piercing itself may potentially lead to serious systemic and local complications.
      The aim of the study was to present three clinical cases of the patients who
      referred to the Dental University Clinic in Krakow for the treatment of lesions
      on the oral mucosa after piercing. Clinicians who examine patients with such body
      decorations should pay particular attention to the sites which can be injured by
      the jewelry. Medical staff should also make patients realize the risk of general
      complications after piercing. This will allow on the early removal of the jewelry
      and prevention of possible complications.

PMID- 24455840
TI  - [Ectopic pancreas imitating gastric neoplasm -- a case report].
AB  - Ectopic pancreas is a rare developmental disorder. Usually is asymptomatic. Most
      frequently is diagnosed in its gastric location accidentally during endoscopy. A
      patient with ectopic pancreas was described manifesting as a gastric tumor
      arousing oncological concern.

PMID- 24455841
TI  - [Herpangina and erythema multiforme in a three-year boy].
AB  - The dentist can be confronted with a vesiculobullous lesion of the oral mucosa
      are a symptoms of herpes infection (herpangina) of throat. Human enteroviruses
      (HEVs) are a major cause of herpangina. Herpangina is an acute viral infection
      caused by certain viruses Coxsackie, is spread by respiratory droplets. The
      infection is mainly encountered in young children. Oral lesions rarely more than
      7 days; treatment is symptomatic. Viral throat infections may accompany various
      skin rashes, such as erythema multiforme (which can also occur without any
      connection with a viral infection). At work was presented a case of 3-year-old
      boy with herpes symptoms of sore throat and mild forms of erythema multiforme.

PMID- 24455842
TI  - [Central Work Camp in Jaworzno (1945-1949) -- epidemiological aspects -- attempt
      of evaluation].
AB  - Publication presents the short history of camp hospital which was organised in
      1943 Nazi concentration camp Neu-Dachs in Jaworzno. The camp was a branch of
      Oswiecim concentration camp. Atfer the war damage of the camp, the restoration
      was begun in 1945. Already in Febraury 1945, in place of German concentration
      camp, rises Central Work Camp. Several thousands of prisoners of war were placed
      there. The prisoners of war: Germans, Volksdeutches, Silesians were forced
      emlpoyed in nearby coal mines. Since 1947 the camp was a place of staying for
      several thousands Ukrainians who were displaced from eastern part of Poland in
      "Vistula Operation". Based on available written materials, publication is an
      attempt to analyse and evaluate: sanitary conditions, prison illnesses, mortality
      reasons among prisoners, hospital equipment, personel work conditions. The
      publication gives opportunity to compare conditions of prison hospital under nazi
      occupation and conditions in the camp which was organised in the same place under
      Stalin system of terror.

PMID- 24455843
TI  - [Traczyk Zygmunt Teodor. Member of the Founding Committee of the Polish
      Urological Association. Biographical note].

PMID- 24455844
TI  - [The Cracow Physicians Society partner of The Medical Facultis Graduates
      Association of The Jagiellonian University in Cracow].

PMID- 24455845
TI  - [Dear colleagues].

PMID- 24455846
TI  - [Expression of E-cadherin and beta1-integrin mRNA in endometrial cancer].
AB  - OBJECTIVES: The metastatic ability of tumors is characteristic for malignant
      neoplasms and constitutes the main cause of therapeutics failures. Metastasis
      formation involves the sequence of processes such as proteolytic degradation of
      the basement membrane, migration, intravasation, extravasation, proliferation and
      angiogenesis. Cadherins and integrins are groups of proteins directly involved in
      these processes. In the present study we analyzed the mRNA expression of CDH1 and
      ITGB1 genes by real-time polymerase chain reaction (RT-PCR). The study included
      106 endometrial carcinomas. CDH1 and ITGB1 mRNA expression was found in all of
      the studied samples. Generally the CDH1 and ITGB1 mRNA expression was
      significantly higher in well-differentiated rather than poorly differentiated
      tumors. MATERIALS AND METHODS: The mRNA expression levels of CDH1 and ITGB1 in
      series of 83 samples of endometrial carcinoma were studied by real time RT-PCR
      method. Statistical analysis of the obtained results was performed. RESULTS: CDH1
      and ITGB1 gene expression was observed in all examined tissues and was correlated
      with cancer malignancy (G). In high grade malignant tumors (G1), CDH1 and ITGB1
      gene expression was the highest, in G2 and G3 tumors the expression of both genes
      was gradually lowering. Moreover the statistically significant correlation
      between CDH1 and ITGB1 gene expression was observed. (Spearman test, r=0.29,
      p<O.01). CONCLUSION: CDH1 and ITGB1 mRNA expression seems to be an important
      marker of cancer progression and metastases in endometrial malignant tumors.

PMID- 24455847
TI  - Relations between combined oral contraceptive therapy and indices of autonomic
      balance (baroreflex sensitivity and heart rate variability) in young healthy
      women.
AB  - INTRODUCTION: There are structural and functional links between autonomic nervous
      and endocrine systems. Derivatives of estrogens and gestagens applied in combined
      oral contraceptives (COC) reduce the production of endogenous sex steroids, but
      their effect on autonomic nervous system remains unknown. AIM: To compare indices
      of heart rate variability (HRV) and baroreflex sensitivity (BRS) among young
      healthy women taking vs. non-taking COC. MATERIAL AND METHODS: We performed a
      cross-sectional study in a group of 53 healthy women (age: 23 +/- 3 years, BMI:
      22.3 +/- 2.8 kg/m(2)) taking COC for > or = 3 months (COC-group) and in a group
      of 113 healthy women (age: 24 +/- 4 years, BMI: 22.0 +/- 3.1 kg/m(2)) not taking
      COC for > or = 3 months (n-COC-group). All examined women were between the 4th
      and the 8th day of menstrual (or pill-driven) cycle lasting from 21 to 35 days.
      Indices of autonomic balance was assessed based on the time- and frequency-
      domains of heart rate variability (HRV very low (VLF), low (LF), high (HF)
      frequencies and total HRV spectrum). BRS was evaluated using the sequence (BRS
      Seq) and the controlled breathing (BRS-CtBr) methods. RESULTS: There were no
      differences in: age, weight, height, measures of adiposity and fat distribution,
      the menstrual (or pill-driven) cycle day on the day of examination, heart rate
      and HRV parameters between the two studied groups (all p > 0.1). BRS-CtBr was
      higher among n-COC-group as compared to COC-group (20.00 +/- 6.28 versus 18.07 +/
      6.57 ms/mmHg, p < 0.05). There was a trend towards higher BRS-Seq in the n-COC
      group as compared to the COC-group (19.4 7 +/- 7.85 versus 16.95 +/- 5.76
      ms/mmHg, p = 0.12). In the n-COC-group, BRS-CtBr and RMSSD were inversely related
      to age (r = -0.23, r = -0.19, p < 0.05). In the COC-group, SDNN was inversely
      related to waist circumference and WHR (respectively r = -0.34 and r = -0.35,
      both p < 0.05). CONCLUSIONS: COC impair the reflex regulation of cardiovascular
      system based on baroreflex, which may indicate unfavorable influence of COC use
      on women health. The exact mechanism of BRS impairment caused by COC remains
      unknown, also in the context of the different composition of various COC. Thus,
      it needs to be studied further

PMID- 24455848
TI  - Markers of insulin resistance in perimenopausal women with endometrial pathology.
AB  - OBJECTIVES: To determine and compare the prevalence of insulin resistance and
      carbohydrate metabolism parameters in women with endometrial pathology MATERIAL
      AND METHODS: 100 perimenopausal women with abnormal uterine bleeding and/or
      abnormal endometrium were included into the study. Hysteroscopy with biopsy was
      performed. The study population was divided into four groups according to
      histopathological results of the endometrium: non-atypical endometrial
      hyperplasia, endometrial polyp, endometrial cancer and controls. Fasting glucose
      and insulin levels and OGTT, IR indexes, occurrence of diabetes, pre-diabetic
      state, overweight, obesity and hypertension were assessed. RESULTS: Insulin
      resistance was diagnosed in 41.0% of the patients. The prevalence of markers of
      insulin resistance increased to 57.1% in cases with confirmed endometrial
      pathology compared to 31.8% in histologically normal endometrium (p<0.01). The
      frequency of insulin resistance was 52.6% (p=0.059) and 55.5% (p=0.04),
      respectively in women with non-atypical hyperplasia and patients with endometrial
      polyps when compared to the control group. Abnormal parameters of carbohydrate
      metabolism indicate little sensitivity and specificity in predicting endometrial
      hyperplastic lesions. The insulin levels at 120 minutes of OGTT correlate best
      with such changes (concentration >57 microU/ml in case of hyperplasia and >61
      microU/ml in endometrial polyps). CONCLUSION: Insulin resistance and carbohydrate
      metabolism disturbances are common in women with endometrial pathologies. In
      these patients there is clinical basis for recommending lifestyle modification
      (change of diet, more physical activity), or for introduction of pharmaceutical
      insulin-sensitizing agents.

PMID- 24455849
TI  - [Cervical cancer incidence and mortality rates including the screening program
      results in the Podkarpackie Region between 1999-2010].
AB  - INTRODUCTION: A continuous decrease in the cervical cancer morbidity and
      mortality rates has been noted in the Podkarpackie Region. A 34.6% and a 23.1%
      drop in the morbidity and mortality respectively was reported between 1999-2010.
      The aim of the study was to analyze the trends of cervical cancer morbidity and
      mortality rates in women of the Podkarpackie Region between 1999-2010. MATERIALS
      AND METHODS: A total of 1898 cervical cancer cases and 883 cervical cancer
      related deaths were analyzed. Crude and standardized morbidity and mortality
      rates, structure ratios and share of cervical cancer cases identified in the
      screening program were formulated. RESULTS: A decrease in cervical cancer
      morbidity by 65 newly diagnosed cases was observed in 2010 in the Podkarpackie
      Region as compared with 1999. Crude and standardized morbidity rates showed a
      tendency to decline, from 17.3/100,000 (standardized ratio 13.9/100,000) in 1999
      to 11.6/100,000 (standardized ratio 8.0/100,000) in 2010. A slight decrease in
      the mortality rate, from 8.4/100,000 (standardized 6.3/100,000) in 1999 to
      6.5/100,000 (standardized 3.6/100,000) in 2010, was noted as well. High
      heterogeneity was observed in cervical cancer morbidity and mortality rates in
      different counties of Podkarpackie in 2010. Morbidity and mortality rates ranged
      between 21.1 - 0.0/100,000 and 35.2 - 0.0/700,000, respectively. The percentage
      share of cervical cancer cases diagnosed in the screening program between 2006
      2010 showed an increase of 0.7%. CONCLUSIONS: Between 1999-2010, the morbidity
      and mortality rates were lower in the Podkarpackie Region as compared to other
      regions of Poland. As far as the counties of the Podkarpackie region are
      concerned, in 2010 the highest morbidity rate in the Krosnienski County was 21
      fold higher than in Kolbuszowski County while the mortality rate in Bieszczadzki
      County was 35-fold higher as compared to Leski County Nizanski County and
      Przemysl city. The percentage share of cervical cancer cases diagnosed in
      screening program increased in 2006-2010 from 4.7% to 5.4%.

PMID- 24455850
TI  - [A comparative analysis of selected parameters of vascular angiogenesis in
      placentas from dizygotic twin pregnancies].
AB  - INTRODUCTION: Most of preIntroduction: Most pregnancies after assisted
      reproduction techniques are dizygotic twin gestations. There is a close
      relationship between the development and functioning of the placenta and the
      growth of both fetuses in dizygotic twin pregnancies. Angiogenesis is the process
      of creating new capillaries. OBJECTIVES: The aim of the study was to compare the
      expression of vascular endothelial growth factor (VEGF) and endothelial nitric
      oxide synthase (eNOs) between placentas of dizygotic twins, taking into account
      their birth weight. MATERIALS AND METHODS: The study included 35 women in
      dizygotic twin pregnancies, resolved after 30 completed weeks of gestation by a
      caesarean section. The patients were divided into two groups: twins whose weight
      did not differ by more than 20% (group 1) and twins whose weight differed by more
      than 20% (group 2). Twins with higher and lower birth weight were classified as A
      and B, respectively A comparative analysis of the placentas of twins A and B with
      regard to the selected parameters of angiogenesis, i.e. VEGF and eNOs, was
      performed. RESULTS: A strong expression of VEGF was observed in twins with lower
      birth weight in group 1, as well as a strong expression of eNOs in twins with
      higher weight in group 2, and with lower weight in group 1. CONCLUSIONS:
      Neovascularization is more expressed in the placentas of twins with lower birth
      weight (in the group with no significant differences in weight), possibly
      reflecting the existence of efficient mechanisms of compensation. High expression
      of e-NOS may indicate an increased risk of ischemia with intact endothelium.

PMID- 24455851
TI  - [Prognostic significance of subchorionic hematoma for the course of pregnancy].
AB  - OBJECTIVES: the aim of this retrospective study was to assess if a first
      trimester subchorionic hematoma (SCH) influences the pregnancy outcome and
      whether pv bleeding can be a prognostic factor for the pregnancy course. MATERIAL
      AND METHODS: the study included 185 pregnant women hospitalized due to symptoms
      of a threatening miscarriage. Patients were divided into 2 groups: 119 women with
      SCH (study group) and 66 patients with normal prenatal scan (control group),
      further subdivided into cases with and without pv bleeding, irrespectively of the
      outcome of the ultrasound scan. Obstetric and neonatal data were analyzed.
      RESULTS: 1. A pregnancy complicated by SCH is more often associated with a poor
      outcome -- 23.78% of the study group patients had a miscarriage versus 7.62% of
      the controls. 2. Pregnancy with SCH is more likely to be lost before 9 weeks of
      gestation. 3. The "N" ratio, that expresses the maximal length of the hematoma to
      the maximal length of the fetus, equal to 2.5 or more, is associated with a risk
      of miscarriage. 4. The surface area of SCH equal to 280mm(2) or more is more
      likely to reveal with vaginal bleeding. 5. Vaginal bleeding can be a prognostic
      factor for the mode of delivery -- a higher rate of the Cesarean section is
      observed in patients with pv bleeding. 6. SCH is a complication that occurs in
      older women, with the limit of 30 years of age. 7. In this study there were no
      significant correlations between subchorionic hematoma or pv bleeding and PTL,
      IUGR, PIH, abnormal volume of the amniotic fluid, parity and order of gestation
      and delivery CONCLUSIONS: subchorionic hematoma can be associated with poor
      pregnancy outcome and the "N" index may be a useful predictor of the further
      course of a pregnancy Pv bleeding may be a prognostic factor for the delivery
      mode.

PMID- 24455852
TI  - Applicability of fetal renal artery Doppler values in determining pregnancy
      outcome and type of delivery in idiopathic oligohydramnios and polyhydramnios
      pregnancies.
AB  - AIMS: To investigate the relationship between fetal renal artery Doppler results
      and pregnancy outcomes in patients with idiopathic abnormal amniotic fluid
      indices. MATERIAL AND METHOD: A total of 110 patients without signs of fetal
      distress were included in the study: 31 idiopathic oligohydramnios and 29
      idiopathic polyhydramnios pregnancies (study group) and 50 normal pregnancies
      (controls). Doppler investigation of the umbilical artery (UA), middle cerebral
      artery (MCA), fetal descendant thoracic aorta (DTA) and fetal renal artery (RA)
      was performed in all patients. Fetal RA resistive index (RI) and pulsatile index
      (PI) values were measured. Values pertaining to type of birth, newborn weight and
      APGAR scores were compared. RESULTS: Average patient age, gravidity and week of
      pregnancy were 25 +/- 4, 1.6, and 37.4 +/- 1, respectively There were no
      statistically significant differences between the groups as far as UA S/D, MCA
      S/D, DTA S/D, DTA RI, DTA PI, and RA S/D measurements were concerned. However in
      the oligohydramnios group RA RI and RA PI values were significantly higher than
      the other two groups. Birth weight in the polyhydramnios group and cesarean
      section rate due to fetal distress in the oligohydramnios group were
      significantly higher CONCLUSIONS: In the oligohydramnios group, without affecting
      fetal distress parameters, Doppler USG evaluation identified an increase in the
      RA resistance. Also in that group, cesarean rate due to fetal distress during
      labor was significantly higher than in the remaining two groups. Due to the
      predictive potential of values of fetal renal artery Doppler of fetal outcome
      further large sample-sized studies on the subject ought to be carried out.

PMID- 24455853
TI  - Contraception for cancer survivors.
AB  - Modern methods of diagnosis and treatment allow for better survival outcomes and,
      more importantly, for higher curability of cancer. Female cancer survivors often
      need effective advice concerning the choice of birth control methods. The
      majority of gynecologists are reluctant to propose anything other than barrier
      methods due to lack of information concerning safe use of more effective
      contraceptives. The aim of the paper was to summarize indications and
      contraindications to different methods of contraception available to cancer
      survivors in Poland.

PMID- 24455854
TI  - [Selected vulvar dermatoses].
AB  - Numerous cutaneous lesions are located in the region of the female genital
      organs, occasionally presenting a diagnostic and therapeutic challenge. The most
      common cases include: eczema vulvae, lichen simplex chronius, lichen sclerosus et
      atrophicus or lichen planus. Clinical presentation of these lesions is not always
      characteristic for certain dermatoses. Thus, it is important to conduct proper
      tests, including histopathological or contact allergy examination. Only thorough
      diagnostics allows to implement correct therapy. This paper shows a detailed
      description of dermal lesions located in the region of the female genital organs
      of the allergic and lichenoid origin, together with the literature review on
      diagnosis and treatment.

PMID- 24455856
TI  - [Children born from frozen embryos stored for 10 years -- analysis of 5 cases].
AB  - Faced with a scientific and legal debate on human embryo cryopreservation in
      Poland we show 5 documented clinical cases of successful thawing and transfer of
      embryos cryopreserved for a long period of time (8-11 years), resulting in
      successful delivery by the biological or the recipient mother. Cases described
      include patients with different infertility diagnoses, subjected to different
      hormonal stimulation treatments. Different oocyte fertilization methods were
      performed, and the obtained embryos were frozen after 2, 3 or 4 days of in vitro
      culture using methods employing various cryoprotective agents and freezing
      curves. As a result of performed thawing and transfer procedures normal, healthy
      babies were born. Our results are consistent with the international reports on
      successful long-term storage of embryos, (including the longest known period of
      over 19 years) resulting in no detectable reduction of the developmental
      potential after thawing. In light of data shown here, we do not see any medical
      or biological reasons for legally-regulated limitation of the period of frozen
      embryo storage. Moreover, if frozen, long-term stored embryos are not threatened
      by destruction and if prenatal adoption is a real, clinically documented option,
      we fail to see any reason for legal limitations of embryo cryopreservation in
      human infertility treatment.

PMID- 24455855
TI  - Uterine artery embolization using gelatin sponge particles performed due to
      massive vaginal bleeding caused by ectopic pregnancy within a cesarean scar: a
      case study.
AB  - A pregnancy located within a cesarean scar is the rarest form of ectopic
      pregnancy. We present a case of a 34-year-old woman with a history of one
      cesarean section (gravida 2, para 1) admitted to the hospital at 9 weeks of
      gestation due to vaginal bleeding, initially diagnosed as a missed abortion.
      During the hospitalization spontaneous abortion took place, and the patient was
      qualified for dilatation and curettage. After the procedure massive vaginal
      bleeding occurred, a cesarean scar pregnancy was diagnosed, and uterine artery
      embolization (UAE) using gelatin sponge particles was performed. The treatment
      was successful. Our case shows that UAE might be a life-saving procedure in
      cesarean scar pregnancy hemorrhages. Absorbable properties of gelatin sponge
      particles reduce the risk of adverse effect on fertility.

PMID- 24455857
TI  - Prenatal diagnosis of Down syndrome in dizygotic twin pregnancy.
AB  - We present a case of a 33-year-old pregnant woman who had a transvaginal
      ultrasound performed at week 9 of gestation. A dichorionic diamniotic twin
      pregnancy with symmetrically developing fetuses, was confirmed. Chromosomal
      defect markers (NT NB, DV TV) were analyzed in the first genetic test, performed
      according to the Fetal Medicine Foundation (FMF) criteria, and the double marker
      test was performed (PAPP-A protein and free beta-hCG concentrations in patient
      serum were determined). In the subsequent diagnostic procedures, the patient was
      offered and consented to amniopuncture after week 15 of gestation. The material
      obtained in the course of that invasive procedure allowed to identify a normal
      male karyotype - 46, XY in the first fetus (Fetus I). Cytogenetic analysis of the
      material from the second fetus (Fetus II) resulted in the diagnosis of an
      abnormal female karyotype - 47, XX, +21. Based on the analyzed clinical case, we
      present the difficulties of performing prenatal diagnosis in a dizygotic twin
      pregnancy The results prove the applicability and efficacy of prenatal
      diagnostics tests based on the FMF criteria also in twin pregnancies.

PMID- 24455858
TI  - [Antistress cross-effects of extracellular metabolites of bacteria, archaea, and
      yeasts: a review].
AB  - This paper reviews examples of specific and global responses of microorganisms
      and the characteristics of stress responses involving extracellular signaling
      metabolites. Information regarding the protective and reactivating effects
      produced by active exometabolites of representatives of domains of bacteria,
      archaea, and eukaryotes is summarized, and interdomain cross-responses to
      stressors are demonstrated.

PMID- 24455859
TI  - [Determination of the antioxidant properties of activators of mitochondrial ATP
      dependent potassium channels with the Amplex Red fluorescent indicator].
AB  - The effect of adaptogens-antihypoxants that participate in the activation of
      mitochondrial ATP-dependent potassium channels (mitoK(ATP)) at the oxidation of
      the Amplex Red (AR) fluorescent indicator in a peroxidase system was tested. It
      was shown that Extralife, Hypoxen, taurine, and synthetic antioxidant ionol can
      be arranged in the following row, according to the fluorescence inhibition
      activity: Extralife > Hypoxen > > ionol > taurine; their effect was shown to be
      concentration-dependent. The calculated K(i) value of fluorescence indicators
      demonstrate fast and slow phases of inhibition of the AR oxidation by Extralife
      and Hypoxen. The fast phase occurs in the presence of microdoses (0.05-3
      microg/mL) of adaptogens and is related to the competition for H2O2, which is in
      agreement with our previous data on the mitoK(ATP) activation by doses of
      adaptogens related to the H2O2 consumption. The slow phase is characteristic of
      high adaptogen and ionol concentrations and is related to the competition for
      phenoxyl radicals of resorufin formed during AR oxidation. The obtained results
      allow one to suggest the application of a highly sensitive model peroxidase
      system with AR for the preliminary testing of compounds activating mitoK(ATP)
      channels.

PMID- 24455860
TI  - Differential fusion expression and purification of a cystatin in two different
      bacterial strains.
AB  - To date, the identification of the novel multifunctional properties of cysteine
      proteinase inhibitors "known as cystatins" is the great of interests for
      molecular biologists. The efficient production, purification and correctly folded
      form of these proteins are the most important requirements for their any basic
      research. To the best of our knowledge, maltose-binding protein (MBP) fusion tags
      are being used to overcome the impediment to their heterologous recombinant
      expression in Escherichia coli as insoluble and bio-inactive inclusion bodies. In
      the present work, to evaluate the expression efficiency of a cystatin molecule in
      E. coli cells by using MBP tags, the expression of Celosia cystatin was studied
      in two different strains of this bacterium. The quantitative analysis results
      based on the one-step purification yield of the fused product showed the
      excellency of the E. coli TB1 strain in comparison to E. coli DH5alpha for the
      high-level production of active product.

PMID- 24455861
TI  - [Transformation of 2- and 4-cyanopyridines by free and immobilized cells of
      nitrile-hydrolyzing bacteria].
AB  - The transformation dynamics of 2- and 4-cyanopyridines by cells suspended and
      adsorbed on inorganic carriers has been studied in the Rhodococcus ruber gt 1
      strain possessing nitrile hydratase activity and the Pseudomonas fluorescens C2
      strain containing nitrilase. It was shown that both nitrile hydratase and
      nitrilase activities of immobilized cells against 2-cyanopyridine were 1.5-4
      times lower compared to 4-cyanopyridine and 1.6-2 times lower than the activities
      of free cells against 2-cyanpopyridine. The possibility of obtaining isonicotinic
      acid during the combined conversion of 4-cyanopyridine by a mixed suspension of
      R. ruber gt 1 cells with a high level of nitrile hydratase activity and R.
      erythropolis 11-2 cells with a pronounced activity of amidase has been shown.
      Immobilization of Rhodococcus cells on raw coal and Pseudomonas cells on china
      clay was shown to yield a heterogeneous biocatalyst for the efficient
      transformation of cyanopyridines into respective amides and carbonic acids.

PMID- 24455862
TI  - [Effect of surface-active substances of Acinetobacter calcoaceticus IMV B-7241,
      Rhodococcus erythropolis IMV Ac-5017, and Nocardia vaccinii K-8 on
      phytopathogenic bacteria].
AB  - The effect of surface-active substances (SAS's) of Acinetobacter calcoaceticus
      IMV B-7241, Rhodococcus erythropolis IMV Ac-5017, and Nocardia vaccinii K-8 on
      phytopathogenic bacteria has been studied. It was shown that the survival of
      cells (10(5)-10(7) in a milliliter) of the Pseudomonas and Xanthomonas
      phytopathogenic bacteria was found to be 0-33% after treatment with SAS
      preparations of the IMV Ac-5017 and IMV B-7241 strains for 2 h (0.15-0.4 mg/mL).
      In the presence of N. vaccinii K-8 SAS preparations (0.085-0.85 mg/mL), the
      number of cells of the majority of the studied phytopathogenic bacteria decreased
      by 95-100%. These data show prospects for using microbial SAS's for the
      construction of ecologically friendly drugs for regulating the number of
      phytopathogenic bacteria.

PMID- 24455863
TI  - [Functional characteristic of the CefT transporter of the MFS family involved in
      the transportation of beta-lactam antibiotics in Acremonium chrysogenum and
      Saccharomyces cerevisiae].
AB  - Vectors for the expression of the CefT transporter of the MFS family in
      Acremonium chrysogenum--a producer of beta-lactam antibiotic cephalosporin C--and
      in Saccharomyces cerevisiae as a fusion with the cyan fluorescent protein (CFP)
      have been created. The subcellular localization of the CefT-CFP hybrid protein in
      yeast cells has been investigated. It was shown that the CefT-CFP hybrid protein
      is capable of complementation of the qdr3, tpo 1, and tpo3 genes encoding for
      orthologous MFS transporters of Saccharomycetes, making the corresponding strains
      resistant to spermidine, ethidium bromide, and hygromycin B. High-yield strain
      VKM F-4081D of A. chrysogenum, expressing the cefT-cfp fusion, was obtained by an
      agrobacteria conjugated transfer. It was also shown that the constitutive
      expression of cefT in A. chrysogenum VKM F-4081D led to a change in the
      biosynthetic profiles of cephalosporin C and its precursors. This resulted in a
      25-35% decrease in the finite product accumulated in the cultural liquid with a
      simultaneous increase in the concentration of its intermediators.

PMID- 24455865
TI  - Inducing effect of salicin for extracellular endoglucanase synthesis in Rhizopus
      oryzae PR7 MTCC 9642.
AB  - The induction of endoglucanase of Rhizopus oryzae PR7 MTCC 9642 has been observed
      in cultivation medium using a batch-fermentation technique. The effect of various
      experimental parameters such as use various carbon sources as inducers,
      concentration of inducer and effect of different additives were investigated.
      Salicin at concentrations from 0.25 to 0.75% (w/v) was found to bring about a
      remarkable increase in endoglucanase synthesis when used as a sole carbon source
      and thought to act as a gratuitous inducer of the enzyme. Endoglucanase activity
      increased within 24 h after the addition of salicin, reached maximum after 48 h
      and maintained high level even after 120 h of fungal growth. Repression of enzyme
      synthesis by glucose could partially be restored by addition of salicin at an
      early phase of growth. The carboxymethyl cellulose induced enzyme was inhibited
      by cyclohexamide and ethidium bromide and partially recovered by the salicin
      which indicated that salicin might act at the transcriptional but not
      translational level.

PMID- 24455864
TI  - [Effect of the steroid molecule structure on the direction of its hydroxylation
      by the fungus Curvularia lunata].
AB  - The main and side products of hydroxylation by the C. lunata VKPM F-981 mycelium
      of fourteen delta(4)-3-ketosteroids of the estrane, androstane, and pregnane
      series and six of their delta(5)-3beta-hydroxy analogues were identified by H1
      PMR spectroscopy and comparison with standard samples. The obtained experimental
      data are considered in terms of the triangular model of the enzyme-substrate
      interaction. The dependence of the direction of hydroxylation of steroid
      molecules and the orientation of hydroxy groups on the structure of the initial
      substrate was revealed.

PMID- 24455866
TI  - Purification and characterization of pectin lyase secreted by Aspergillus flavus
      MTCC 10938.
AB  - An indigenously isolated fungal strain Aspergillus flavus MTCC 10938 was
      subjected to pectin lyase (PNL) production under submerged fermentation
      conditions. The enzyme was purified to homogeneity from the culture filtrate of
      the fungus involving concentration by ultrafiltration, anion exchange
      chromatography on DEAE cellulose and gel filtration chromatography on Sephadex G
      100. The purified PNL gave a single protein band in SDS-PAGE analysis with a
      relative molecular mass corresponding to 50 kDa. Using citrus pectin as the
      substrate the K(m) and k(cat) values of the enzyme lyase were obtained as 1.7
      mg/mL and 66 s(-1), respectively. The optimum pH of the purified PNL from A.
      flavus MTCC 10938 was 8.0 and up to 90% of its activity retained in the pH range
      from 3.0 to 11.0 after 24 h incubation. The optimum temperature of the purified
      enzyme was revealed at 55 degrees C and it was completely stable up to 40 degrees
      C when exposed for 30 min. The purified A. flavus MTCC 10938 PNL showed efficient
      retting of Crotalaria juncea fibres.

PMID- 24455867
TI  - [Biological synthesis of gold nanoparticles by the xylotrophic basidiomycete
      Lentinula edodes].
AB  - This is the first study to demonstrate that the medicinal basidiomycete Lentinula
      edodes can reduce gold (III) ions from hydrogen tetrachloaurate (chloroauric
      acid) H[AuCl4] to the elementary state with the formation of spherical
      nanoparticles (nanospheres). When a culture was grown under submerged conditions
      in the presence of chloroauric acid, the appearance of an intense purple-red
      color of L. edodes filamentous hyphae was recorded, which indicates that gold
      ions were reduced to gold nanoparticles. Using transmission electron microscopy
      and X-ray fluorescence, we observed accumulation of colloidal gold by the fungal
      mycelium in the form of electron-dense nanospheres of 5 to 50 nm in diameter on
      the surface and inside fungal cells.

PMID- 24455868
TI  - [Effect of the rol genes from Agrobacterium rhizogenes on the content and
      structure of pectic substances and glycanase activity in Rubia cordifolia
      transgenic cell cultures].
AB  - The expression of the rolB gene was found to increase the pectic yield in Rubia
      cordifolia cells, while the rolC gene inhibited the pectin production, which
      correlated with its expression level. The expression of the rolA, rolB, and rolC
      genes led to an increase in the content of arabinogalactan (AG) in cells. The
      increase in the expression of the rolB and rolC genes resulted in a more
      significant reduction in the content of arabinose residues in pectin, which was
      accompanied by an increased activity of alpha-L-arabinofuranosidase in cells.
      Moreover, the amount of galactose residues in pectin increased with the
      enhancement of the rolB expression due to a decrease in the activity of beta
      galactosidase in cells. The content of galacturonic acid residues in pectin from
      transgenic cultures increased in the following order: rolC < rolB < rolA. The
      amount of arabinose residues in AG decreased independently of the gene type. The
      amount of arabinose residues in AG was found to be considerably reduced when the
      rolB expression level was increased.

PMID- 24455869
TI  - [Isolation of D-glucosamine from chitin-glucan complexes].
AB  - The peculiarities of the acidic hydrolysis of chitin-glucan complexes (CGCs) of
      higher fungi were studied, and the technology for the isolation and purification
      of D-(+)-glucosamine hydrochloride of high purity from hydrolysate was developed.
      The composition, properties, and purity of the product were analyzed by a
      combination of physicochemical methods. The yield of the final product was 20
      60%, depending on the chitin content in CGC samples. The amino sugar obtained was
      a white crystalline odorless powder readily soluble in water, slightly soluble in
      95% ethanol, and insoluble in chloroform and other organic solvents. It
      corresponds to the standard D-(+)-glucosamine hydrochloride in the main
      qualitative indicators.

PMID- 24455870
TI  - [Effect of oregano essential oil on the engraftment and development of Lewis
      carcinoma in F1 DBA C57 black hybrid mice].
AB  - The effect of a low uptake dose of oregano essential oil with drinking water for
      three months (Origanum vulgare L.) on the degree of Lewis carcinoma engraftment
      and some parameters of oxidative stress has been studied in vivo using F1 DBA C57
      Black hybrid mice. Oregano essential oil has been established to possess an
      anticancer activity. The degree of tumor engraftment decreased by 1.8 times, its
      size decreased by 1.5 times, and the development of tumor was significantly
      suppressed in sick mice under the effect of oregano essential oil. It was found
      that the uptake of essential oil did not affect the intensity of lipid
      peroxidation in the brain of mice and resulted in a significantly (by 36%)
      decreased content of secondary lipid oxidation products in the liver as shown in
      a reaction with thiobarbituric acid as compared to control subjects. The activity
      of antioxidant enzymes was found to increase after three months of essential oil
      uptake (by 1.5-3 times) as compared to the control group. This effect of
      essential oil supports the presence of bioantioxidant properties in this
      essential oil.

PMID- 24455871
TI  - [Results of the study of the geographical variability of the parasite fauna and
      of the structure of component communities of the minnow parasite Phoxinus
      phoxinus (L.) 1. Basins of the Kama and Northern Dvina Rivers].
AB  - In the basin of the Kama River, in upper Vychegda River, and in tributaries of
      the upper Northern Dvina River, the parasite fauna of the minnow is monotonous
      and component communities of parasites are mature (balanced, according to
      Pugachev, 1999). They are completely formed in June.

PMID- 24455872
TI  - [Localization of crustaceans--fish parasites and nose capsules as the habitat of
      the genus Salmincola (Podoplea: Lernaeopodidae) mesoparasites].
AB  - Copepoda parasitica of Baikal fishes (16 species) is divided into 7 groups
      according to their localization: parasites of the gill apparatus, gill covers,
      gill and buccal cavities, nasal fossa, cutaneous covering, and fins. It was
      proposed to separate nasal fossa parasites as the special ecological group
      ofmesoparasites. Typical speciemens of the group include crustaceans Salmincola
      longimanus complex--parasites of grayling and cisco fishes consist of three
      species (S. longimanus, S. svetlanovi, S. lavaretus) and one subspecies (S.
      longimanus sibirica).

PMID- 24455873
TI  - [Parasites of the Osprey (Pandion haliaetus) in northwestern Russia].
AB  - New data on Ospey parasites in Karelian Republic are given. One specimen was
      investigated. Two parasite species--Nematostrigea serpens and Diplostomum
      pseudospathaceum were found. Trematoda D. pseudospathaceum was recorded in Osprey
      parasite fauna for the first time.

PMID- 24455874
TI  - [Trematodes of birds (Aves) from the Middle Volga region. 2. Orders
      Plagiorchiida, Renicolida, Strigeida, and Schistosomatida].
AB  - Data on trematodes of Plagiorchiida, Renicolida, Strigeida, and Schistosomatida,
      parasitizing in birds of the Middle Volga region are given. Proceedings of the
      different authors are supplemented by results of our research. Two species of
      trematodes (Brachylaima mesostoma and Mosesia amplavaginata) are specified for
      birds of the middle Volga region for the first time. New hosts were revealed for
      2 trematode species: the great tit for Plagiorchis laricola and the common
      chaffinch for M. amplavaginata. The following characteristics for each parasite
      are given: it's systematic position, the spectrum of hosts, localization,
      collecting site, biology, the degree of host specificity and geographical range.
      The morphological description and original figures of 11 species of trematodes
      are presented.

PMID- 24455875
TI  - [Reproduction of trematode Leucochloridium paradoxum sporocysts (Trematoda:
      Leucochloridiidae)].
AB  - The histological study of the trematoda sporocysts Leucochloridium paradoxum
      confirmed the presence of three morphological zones in it: 1) central part
      (reproductive), where embryos are forming, 2) narrow tubes through which the
      embryos penetrate in colored broodsacs (3), where the development of metecercaria
      completes. It was found that germinal mass only is the reproduction organ of the
      sporocysts, located in reproductive zone. There are young (without embryos),
      mature (with embryos) and degenerated germinal masses. So, in the process of
      sporocysts development the centre of multiplication of germinal elements was
      changed. The old parts of central part are degenerated, but the new ones with
      young germinal masses appear. The multiplication of generative elements does not
      take place in the broodsacs which are breeding cameras functionally.

PMID- 24455876
TI  - [Dynamics of kinks in inhomogeneous polynucleotide chains].
AB  - In the present paper the dynamics of the nonlinear conformational excitations-
      kinks, in inhomogeneous polynucleotide DNA chains is investigated. To calculate
      the kink rest energy E0 and its length d the method of dynamical interval is
      used. This makes it possible to take into account that all coefficients of the
      model dynamic equation--the sine-Gordon equation depend on the sequence of bases.
      It is shown that the method gives an opportunity to calculate dynamical
      characteristics of any artificial and real sequences that is important for
      implementing tasks associated with the search and analysis of functionally
      important DNA sites.

PMID- 24455877
TI  - [NMR studies of water-gas interactions].
AB  - The analysis of reported data concerning the solubility of different gases in
      water depending on a temperature was carried out. These dependences could be
      described by mono- or biexponential function. Solubilities of nitrogen and oxygen
      are additive and depend on their percentage in the atmosphere above the fluid.
      The temperature dependence of oxygen and nitrogen dissolved in water corresponds
      to that in the atmospheric air. The measurements of water spin-lattice relaxation
      times changing upon the concentration of dissolved paramagnetic oxygen showed
      that the oxygen could be significantly but not completely eliminated by
      saturation with any gases. The best method is the contact with a water immiscible
      liquid with higher gas capacity than water. However, it results in unstable state
      of a gas-water system converging to equilibrium.

PMID- 24455878
TI  - [Evaluation of prooxidant properties of ascorbic acid].
AB  - Chemiluminescence of ascorbic acid in Fenton solution was investigated at acid
      concentration from 10(-7) to 1 mol/l. The yield of chemiluminescence exceeds
      spontaneous light from Fenton solution at [Asc] - 10(-4) - 10(-3) mol/l in the
      presence of dissolved oxygen, and prooxidant properties are displayed. When there
      is no oxygen in solution, this effect is not observed. A comparison of
      experimental data and oxidation process simulation shows that ascorbic acid is an
      antioxidant. Its transformation products in the presence of oxygen exert
      prooxidant properties.

PMID- 24455879
TI  - [Spatial structure of Thr-Pro-Ala-Glu-Asp-Phe-Met-Arg-Phe-NH2 molecule].
AB  - The spatial structure of cardioactive Thr-Pro-Ala-Glu-Asp-Phe-Met-Arg-Phe-NH2
      molecule has been investigated using a theoretical conformational analysis. The
      low-energy conformations of the molecule were found, the values of the backbone
      and side T-T chain dihedral angles of amino acid residues constituting the
      peptide were determined, and the energies of intra- and interresidual
      interactions were estimated. It is revealed that the spatial structure of this
      molecule can exist in 11 stable backbone forms.

PMID- 24455880
TI  - [Thermodynamic parameters of stabilization in a compact form of the Caf1(13-149)
      subunit from Yersinia pestis].
AB  - With a number of experimental methods (circular dichroism, viscosity, intrinsic
      fluorescence and fluorescence labelling) the conformational folding-unfolding
      transitions in a compact monomeric form of the Caf1(13-149) subunit were studied
      under the action of guanidine hydrochloride in the temperature range from 5 to 45
      degrees C. It has been shown that transitions always occur between two major
      states (unfolded and compact). It has made it possible to determine all main
      thermodynamic functions that characterize the compact state of the Caf1(13-149)
      subunit: temperature stability T(m), the free energy of stabilization deltaG(st),
      enthalpy deltaH(tr) and heat capacity jump deltaC collapse of the structure. Data
      obtained have been confirmed by an independent experiment on melting of
      fluorescently labeled proteins.

PMID- 24455881
TI  - [Protein conformational dynamics of crambin in crystal, solution and in the
      trajectories of molecular dynamics simulations].
AB  - Atomic displacement parameters--B factors of the eight crambin crystal structures
      obtained at 0.54-1.5 angstroms resolution and temperatures of 100-293K have been
      analyzed. The comparable contributions to the B factor values are the
      intramolecular motions which are modeled by the harmonic vibration calculations
      and derived from the molecular dynamics simulation (MD) as well as rigid body
      changes in the position of a protein molecule as a whole. In solution for the
      average NMR structure of crambin the amplitudes of the backbone atomic
      fluctuations of the most residues of the segments with the regular backbone
      conformations are close to the amplitudes of the small scale harmonic vibrations.
      For the same residues the probability of the medium scale fluctuations fixed by
      the hydrogen exchange method is very low. The restricted conformational mobility
      of those segments is coupled with the depressed amplitudes of the fluctuation
      changes of the tertiary structure registered by the residue accessibility changes
      in an ensemble of NMR structures that forms the average NMR structure of crambin.
      The amplitudes of temperature fluctuations of backbone atoms and the tertiary
      structure raise in the segment with the irregular conformations, turn and loops.
      In the same segments the amplitudes of the calculated harmonic vibrations also
      increase, but to a lesser extent and especially in the interhelical loop with the
      most strong and complicated fluctuation changes of the backbone conformation. In
      solution for the NMR structure in this loop the conformational transitions occur
      between the conformational substates separated by the energy barriers, but they
      are not observed even in the long 100 ns trajectories from the MD simulation of
      crambin. These strong local fluctuation changes of the structure may play a key
      role in the protein functioning and modern performance improvements in the MD
      simulation techniques are oriented to increase the probability of protein
      appearance in the trajectories from the MD simulations.

PMID- 24455882
TI  - [Investigation of the conformational dynamics of the adenosine A2A receptor by
      means of molecular dynamics simulation].
AB  - In this work structural behavior of apo form of the adenosine A2A receptor in the
      implicit membrane-mimicking environment was investigated by means of molecular
      dynamics (MD) technique. For better interpretation of the obtained data they were
      analyzed using principal components analysis. The principal components analysis
      technique was applied to both MD snapshots as well as X-ray structures of the
      adenosine receptor. As the result the charts were obtained which reflected an
      interconnection interdependence between dynamic behavior of the receptor observed
      on the MD trajectories as well as experimental dataset of investigated protein.
      The calculated MD trajectories allow to observe represent pronounced structural
      dynamics of the A2A receptor especially in the intracellular part loop connecting
      TM 5 and 6 of that protein. This observation generally corresponds to the dynamic
      behavior of the investigated protein seen on the experimental dataset. Therefore
      the pattern of the intramolecular motions might be following directly from the
      spatial architecture (fold) of the receptor under study.

PMID- 24455883
TI  - [Structural and functional properties of inulinases. Ways to regulate their
      activity].
AB  - The presented review is devoted to the analysis of structural and functional
      properties of inulinases from various producers. A special attention is given to
      the questions of molecular and permolecular organization of enzymes, description
      of their functional features depending upon their structural conditions and in
      various microenvironment. Perspectives of the development of biotechnological
      processes with the use of free and immobilized inulinases are discussed from a
      biophysical viewpoint.

PMID- 24455884
TI  - [On general physical aspects of a problem of in vivo effective detection and
      recognition of malignant cells].
AB  - A fundamentally new recognition method of bio-objects (in particular malignant
      cells) that escape the immune system supervision control is suggested.
      Recognition of such bio-objects should be carried out by the unified complex
      consisting of several molecular groups (for example, antibodies) bound to each
      other, each group identifies on a surface of this bio-object its target binding
      site. The choice of such targets is determined by a specific surface-antigen
      expression profiling. Thus the efficiency of recognition appears to be many times
      higher, than that in a situation when these molecular groups do not form a
      uniform complex and operate separately. The possibilities of destruction of such
      recognized cells are discussed.

PMID- 24455885
TI  - [On the mechanism for stabilizing a long-living charge separated state of
      photosynthetic reaction centers frozen under intensive illumination].
AB  - It is shown that freezing of the photosynthetic reaction centers from purple
      bacteria Rhodobacter sphaeroides under intensive illumination leads to the
      appearance of long-living charge separated states of reaction centers (P(+)QA-).
      This implies that the recombination reactions is blocked or charge separated
      state is stabilized. Experimental data are presented. It is also shown that this
      stabilization effect is caused by the structural relaxation of reaction centers
      to a new equilibrium state, and the free energy difference decreases as a result
      of this relaxation. The possible mechanism of such relaxation is determined by
      the effect of the polar water molecules orientation in the semiquinone local
      electrostatic field. The detailed analysis of the stabilization effect has been
      carried out, and its result supports a hypothesis of non equilibrium state of
      many electron transfer reactions in biological systems.

PMID- 24455886
TI  - [Univalent ions in phospholipid model membranes: thermodynamic and hydration
      aspects].
AB  - By means of differential scanning calorimetry, effects of systematic series of
      Group I and VII ions on the phase state of model multibilayer
      dimyristoylphosphatidylcholine (di(14:0)PC) membranes have been studied at a
      lipid/ion molar ratio of 3/1. The sign-changing correlations between the ionic
      radii of cations and temperature shifts of di(14:0)PC phase transition were
      obtained. For cosmotropic Li+ and Na+, the observed shifts were positive (LiCl:
      deltaT(m) = 0.6 degrees C; deltaT(p) = 1.9 degrees C), whereas chaotropic K+ and
      Rb+ presence resulted in negative shifts (RbCl: deltaT(m) = -0.3 degrees C;
      deltaT(p) = -2.5 degrees C). The anions (Cl-, Br-, I-) showed a similar effect
      increasing with the ions chaotropicity. An essentially weaker effect of Cs+ as
      compared to other alkali metal ions (CsCl: deltaT(m) approximately 0 degrees C;
      deltaT(p) = -0,1 degrees C) can be one of the reasons of its accumulation in
      living organisms. Generalization of all available data allowed us to specify some
      important factors of lipid-ion interactions that should be taken into account in
      further investigations in this field.

PMID- 24455887
TI  - [Changes in ion transport through membranes, ATPase activity and antibiotics
      effects in Enterococcus hirae after low intensity electromagnetic irradiation of
      51,8 and 53,0 GHz frequencies].
AB  - It was ascertained that one-hour exposure of Enterococcus hirae ATCC9790 bacteria
      grown under anaerobe condition during sugar (glucose) fermentation to coherent
      electromagnetic irradiation (EMI) of 51,8 and 53,0 GHz frequencies or millimeter
      waves (5,79 and 5,66 mm wavelengths) of low-intensity (flux capacity of 0,06
      mW/sm2) caused a significant decrease in energy-dependent H+ and K+ transports
      across the membranes of whole cells. Therewith, K+ influx into cells was
      appreciably less at the frequency of 53,0 GHz. Likewise, a significant decrease
      of total and N,N'-dicyclohexylcarbodiimide-sensitive ATPase activity of the
      membrane vesicles occurred after EMI of 51,8 and 53,0 GHz. These results
      indicated the input of membranous changes in bacterial action of low intensity
      extremely high frequency EMI, when the F0F1-ATPase was probably playing a key
      role. Additionally, the enhancement of the effects of antibiotics--ceftriaxone,
      kanamycin and ampicillin at their minimal inhibitory concentrations (100, 200 and
      1,4 microM, correspondingly) on the bacterial growth by these irradiations was
      shown. Also, combined action of EMI and antibiotics depressed strongly H+ and K+
      fluxes across membrane. Especially, H+ flux was more sensitive to the action of
      ceftriaxone, but K+ flux was sensitive to kanamycin. All these made the
      assumption that EMI of 51,8 and 53,0 GHz frequencies, especially 53,0 GHz, was
      followed by change in bacterial sensitivity toward antibiotics that was more
      obvious with ceftriaxone and ampicillin.

PMID- 24455888
TI  - [Human serum albumin modified under oxidative/halogenative stress enhances
      luminol-dependent chemiluminescence of human neutrophils].
AB  - It is shown that human serum albumin, previously treated with HOCl (HSA-Cl),
      enhances luminol-dependent chemiluminescence of neutrophils activated by phorbol
      12-myristate-13-acetate (PMA). The enzyme-linked immunosorbent assay revealed
      that addition of HSA-Cl to neutrophils promotes exocytosis of myeloperoxidase.
      Inhibitor of myeloperoxidase--4-aminobenzoic acid hydrazide, without any effect
      on lucigenin-dependent chemiluminescence of neutrophils stimulated with PMA,
      effectively suppressed luminol-dependent chemiluminescence (IC50 = 20 microM)
      under the same conditions. The transfer of the cells from medium with HSA-Cl and
      myeloperoxidase to fresh medium abolished an increase in PMA-induced luminol
      dependent chemiluminescence, but not the ability of neutrophils to respond to re
      addition of HSA-Cl. A direct and significant (r = 0.75, p) correlation was
      observed between the intensity of PMA stimulated neutrophil chemiluminescence
      response and myeloperoxidase activity in the cell-free media after
      chemiluminescence measurements. These results suggest the involvement of
      myeloperoxidase in the increase of neutrophil PMA-stimulated chemiluminescence
      response in the presence of HSA-Cl. A significant positive correlation was found
      between myeloperoxidase activity in blood plasma of children with severe burns
      and the enhancing effects of albumin fraction of the same plasma on luminol
      dependent chemiluminescence of PMA-stimulated donor neutrophils. These results
      support a hypothesis that proteins modified in reactions involving
      myeloperoxidase under oxidative/halogenative stress, stimulate neutrophils,
      leading to exocytosis of myeloperoxidase, a key element of halogenative stress,
      and to closing a "vicious circle" of neutrophil activation at the inflammatory
      site.

PMID- 24455889
TI  - [Growth peculiarities of commensal Escherichia coli isolates from the gut
      microflora in Crohn's disease patients].
AB  - Verhulst's logistic differential equation, popular in mathematical ecology, is
      used in modeling of population growth, neural networks, statistics, reaction
      models, Fermi distribution, modeling of tumor growth, etc. We used this function
      to characterize growth of commensal Escherichia coli isolates from gut microflora
      in Crohn's disease patients. The results of our investigations show differences
      in growth parameters of commensal E. coli, isolated from the gut microflora in
      Crohn's disease patients and healthy volunteers; it is most likely explained by
      the influence of chronic inflammatory processes on growth and reproduction of
      these bacteria. It has been established that the used mathematical model well
      characterizes growth of patients' gut E. coli isolates, and it can be important
      for the expedient probiotics' application during the disease.

PMID- 24455890
TI  - [Effect of decimeter polarized electromagnetic radiation on germinating capacity
      of seeds].
AB  - The effect of a polarization structure of electromagnetic radiation on the
      germinating capacity of seeds of such weeds as Green foxtail (Setaria viridis)
      and Green amaranth (Amaranthus retroflexus) has been studied. Seeds have been
      exposed to impulse electromagnetic radiation in a frequency of 896 MHz with
      linear, elliptical right-handed and elliptical left-handed polarizations at
      different power flux density levels. It is determined that the effect of the
      right-handed polarized electromagnetic radiation increases and the influence of
      the left-handed polarized one reduces the germinating capacity of seeds compared
      to the effect of the linearly polarized electromagnetic radiation. It is shown
      that the seeds have an amplitude polarization selectivity as evinced by the major
      effect of the right-handed polarized radiation on seeds. An electrodynamic model
      as the right-handed elliptically polarized antenna with the given quantity of the
      ellipticity of polarization is suggested to use in description of this
      selectivity.

PMID- 24455891
TI  - [Models of fetal ECG recorded on the pregnant woman's abdomen].
AB  - The article presents a literature review devoted to a description of electrical
      potentials of the fetus heart on the pregnant woman's abdomen using the model
      dipole generator. The main results of the model evaluation of the influence of
      extracardiac factors on the fetal ECG during pregnancy and of a choice of a
      preferable location of electrodes on the maternal abdomen are given. The fetal
      ECG models for evaluating signal filtering algorithms are described.

PMID- 24455892
TI  - [Can solar/geomagnetic activity restrict the occurrence of some shellfish
      poisoning outbreaks? The example of PSP caused by Gymnodinium catenatum at the
      Atlantic Portuguese coast].
AB  - Cyclic outbreaks of accumulation of paralytic shellfish poisoning (PSP) toxins in
      mussels attributed to Gymnodinium catenatum blooms displayed several of the
      highest inter-annual maxima coincidental with minima of the 11-year solar sunspot
      number (SSN) cycle. The monthly distribution of PSP was associated with low
      levels of the solar radio flux, a more quantitative approach than SSN for
      fluctuations in solar activity. A comparison between monthly distribution of PSP
      and other common biotoxins (okadaic acid (OA), dinophysistoxin-2 (DTX2) and
      amnesic shellfish poisoning (ASP) toxins) demonstrated that only PSP was
      significantly associated with low levels of radio flux (p < 0.01). PSP occurrence
      suggests a prior decline in solar activity could be required to act as a trigger,
      in a similar manner to a photoperiodic signal. The seasonal frequency increased
      towards autumn during the study period, which might be related to the progressive
      atmospheric cut-off of deleterious radiation associated with the seasonal change
      in solar declination, and might play an additional role in seasonal signal
      triggering. PSP distribution was also associated with low levels of the
      geomagnetic index Aa. A comparison between monthly distribution of PSP and other
      common biotoxins, also demonstrated that only PSP was significantly associated
      with low levels of the Aa index (p < 0.01). In some years of SSN minima no
      significant PSP-outbreaks in mussels were detected. This was attributed to a
      steady rise in geomagnetic activity that could disrupt the triggering signal.
      Global distribution patterns show that hotspots for G. catenatum blooms are
      regions with deficient crustal magnetic anomalies. In addition to the variable
      magnetic field mostly of solar origin, static fields related to magnetized rocks
      in the crust and upper mantle might play a role in restricting worldwide
      geographic distribution.

PMID- 24455893
TI  - [Influences of solar and geomagnetic activity on health status of people with
      various nosological forms of diseases].
AB  - Statistical analysis of correlation between heliogeophysical factors and a
      symptom of the various forms of diseases (based on statistical data on disease of
      the personnel of Irkutsk Scientific Centre, RAS) has been studied. It is shown
      that geomagnetic storms influence vegetative regulation of a cardiac rhythm and
      vascular tone. The most serious consequences of such influence can mainly be
      observed in the persons suffering from diseases of the cardiovascular system
      (consequences of myocardium attack, brain strokes, cardiac rhythm disorders);
      being in a condition of additional stress, mainly with vegetovascular and
      hypertensic crises; having mental diseases; and subject to aggravations of
      general diseases (chronic inflammatory diseases of gynecological,
      musculoskeletal, urinary excretory, bronchopulmonary systems, and systems of
      digestive organs).

PMID- 24455894
TI  - [Cybernetics and biology].
AB  - Owing to methodical disadvantages, the theory of control still lacks the
      potential for the analysis of biological systems. To get the full benefit of the
      method in addition to the algorithmic model of control (as of today the only used
      model in the theory of control) a parametric model of control is offered to
      employ. The reasoning for it is explained. The approach suggested provides the
      possibility to use all potential of the modern theory of control for the analysis
      of biological systems. The cybernetic approach is shown taking a system of the
      rise of glucose concentration in blood as an example.

PMID- 24455895
TI  - [Functional properties of taste bud cells. Mechanisms of afferent
      neurotransmission in Type II taste receptor cells].
AB  - Taste Bud cells are heterogeneous in their morphology and functionality. These
      cells are responsible for sensing a wide variety of substances and for
      associating detected compounds with a different taste: bitter, sweet, salty, sour
      and umami. Today we know that each of the five basic tastes corresponds to
      distinct cell populations organized into three basic morpho-functional cell
      types. In addition, some receptor cells of the taste bud demonstrate glia-related
      functions. In this article we expand on some properties of these three
      morphological receptor cell types. Main focus is devoted to the Type II cells and
      unusual mechanism for afferent neurotransmission in these cells. Taste cells of
      the Type II consist of three populations detecting bitter, sweet and umami
      tastes, and, thus, evoke a serious scientific interest.

PMID- 24455896
TI  - [Contemporary electroencephalographic research on addictive disorders].
AB  - The aim of the work is an integration of contemporary electroencephalographic
      data on addictive disorders. A search in e-library, PubMed, EBSCO and Springer
      databases permitted us to define some of main directions (predisposition, effect
      of single intake, of dependence, abstinence, and role of comorbidities) and
      techniques (visual, spectral and coherence analysis, evoked potentials and
      oscillations) of investigations in that field. Methodology involved in the cited
      works was taken into account during the process of summarization of results.

PMID- 24455897
TI  - [The physiological significance of proliferative and alterative processes].
AB  - This article is a brief review of publications dedicated to a problem of basic
      regularities of proliferative and alternative processes in health and disease and
      their physiological, general biological and special meaning. Historical
      background shows the evolution of scientists' viewpoints regarding essentials and
      reasons of diseases. The publication spotlights systematization of proliferative
      and alternative reactions in different pathophysiological processes. It is
      underlined that the development of morbid conditions can start not only with
      structural-functional changes, but also with failure of physiological processes
      of regulation. A principle of universality and balance of cell and humeral
      responses is taken as a basis of humoral-cell proliferation, which is provided,
      on one side by their conservatism and on the other side by their flexibility.
      Modern investigations confirm that various physiological reactions of
      proliferation in organism are allelically determined more frequently, and their
      disturbances may have epigenetic character. The main physiological meaning of
      proliferative and destructive processes remains their protective-adaptive role in
      organism, and their study and diagnostics keep an important section in
      recognition of various pathophysiological states.

PMID- 24455898
TI  - [The phenomenon of release activity and the hypothesis of "spatial" homeostasis].
AB  - When analyzing the technology of multiple sequential reductions in concentration
      of parent substance we have discovered a novel physical phenomenon. It was shown
      that dilutions of parent substance prepared using this technology have one common
      peculiarity - they are capable to exert direct modifying effect on parent
      substance altering spatial structure of parent substance and consequently its
      physical, chemical and biological properties. Technologically processed dilutions
      also exert activity when they do not contain molecules of parent substance. We
      have defined a newly revealed modifying activity manifested in the process of
      multiple sequential reductions in concentrations and associated with vehicle as
      release-activity while the drugs exerting modifying activity we have called
      release-active drugs. Having analyzed the ceffects of a drug in the whole range
      of doses - toxic, therapeutic, low doses as well as release-active form of a drug
      we came to a conclusion that there were supramolecular spatial matrices with the
      structure, which was identical to the one of a certain substance, and combines
      body molecules into semantic molecular assemblies. All biological systems unlike
      nonliving nature have dual structure - both individual and specific ones.
      Enhancement in any body spatial complexity is its key feature from the point of
      view of evolution development; that is why all processes - both normal
      physiologic and pathologic ones - shall comply with superiority of preservation
      of a body spatial structure hierarchy (hypothesis of spatial homeostasis).

PMID- 24455899
TI  - [Metabolic features in chondroitin sulfate in the normal functioning of
      connective tissue].
AB  - In the propoced review, the literature data on the metabolic characteristics of
      chondroitin sulfate in the normal functioning of connective tissue. Described
      their own data on the study of the reaction of connecting structures of the knee
      rabbits experimental arthritis by intra-articular intra-articular injection of
      chondroitin sulface (the drug "mukosat").

PMID- 24455900
TI  - [Physiological features of skin ageing in human].
AB  - The issue deals with the actual problem of gerontology, notably physiological
      features of human skin ageing. In the present review the authors have considered
      the kinds of ageing, central factors, affected on the ageing process (ultraviolet
      radiation and oxidation stress), as well as the research guidelines of the ageing
      changes in the skin structure and fuctions: study of mechanical properties,
      microcirculation, pH and skin thickness. The special attention has been payed to
      the methods of assessment of skin blood flow, and to results of investigations of
      age features of peripheral microhemodynamics. The laser Doppler flowmetry
      technique - one of the modern, noninvasive and extensively used methods for the
      assessmant of skin blood flow microcirculation system has been expanded in the
      review. The main results of the study of the ageing changes of skin blood
      perfusion using this method has been also presented.

PMID- 24455901
TI  - [An overview of the pulmonary sensory receptors].
AB  - The optimum realization to respiratory function depends on varied sensory
      feedbacks from ensemble of the sources of the body. Pulmonary sensory receptors
      are the initiating sites for lung reflexes. The information arriving from lungs
      and airways information is one of the most important feedbacks that provide the
      adaptation of the respiratory centre for producing of the pattern optimal in
      terms of work and force of breathing. In article the review of data existing
      currently about morphology and functional characteristics of three types of the
      pulmonary structures is presented: slowly adapting stretch receptors, rapidly
      adapting receptors, C-fiber receptors and neuroepithelial bodies.

PMID- 24455902
TI  - [In memory of Yuri Sergeevich Balashov (25.XII.1931-28.IX.2012)].
AB  - Biographical notes describe the life and scientific activities of Yuri Balashov,
      an outstanding Russian parasitologist, the Chief Editor of Parazitologiya.

PMID- 24455903
TI  - [On the contribution of Prof. Yu. S. Balashov to the fundamental parasitology].
AB  - Brief review of main conceptions of Yu. S. Balasov in fundamental parasitology:
      types of host-parasite relations, evolution, transmissive infections, econiches,
      population structure, parasite communities.

PMID- 24455904
TI  - [The main evolutionary trends in sensory organs and questing behavior of
      parasitiform ticks and mites (Parasitiformes)].
AB  - Studies of sensory organs in parasitiform mites by methods of scanning and
      transmitting electron microscopy and electrophysiology in Russia were initiated
      by Yu. S. Balashov. A review of the material accumulated since that time allows
      revealing the main trends in evolution of the morphology the main complicated
      sense organs (the Haller's organ, palpal and tarsal organs, and eyes). Tight
      correlation between the evolution of the questing behavior and of sensory organs
      was demonstrated.

PMID- 24455905
TI  - [Is parasitism of Metazoa "a one-way ticket"?].
AB  - Various data considered as possible cases where metazoans return form the
      obligate parasitism to free mode of life (a violation of ecological
      interpretation of Dollo's law). It is shown that among temporary and phase
      parasites their return to the free mode of life is a rare but not exceptional
      phenomenon. It is possibly to conclude that these cases are displayed only by
      those ectoparasitic arthropods, ancestors of which were predators. The only,
      although incompletely proven cases of the violation of Dollo's law among
      permanent parasites is suggested to be acariform mites of the family
      Pyroglyphidae (Acariformes: Psoroptoidea).

PMID- 24455906
TI  - [Studies of the biological age in adult taiga ticks Ixodes persulcatus
      (Ixodinae)].
AB  - The history of studies of the biological age in ixodid ticks is discussed. A
      method of estimation of the biological age in adult ticks of the genus Ixodes by
      the degree of fat inclusions in midgut cells and in the fat body is developed. An
      "age scale" for the determination of the calendar age was assumed.

PMID- 24455907
TI  - [Dermal glands of water mites (Acariformes: Parasitengona: Hydrachnidia) and
      their possible eco-physiological significance].
AB  - Functional and comparative morphology is the basis for investigation of animal
      kingdom, its diversity and possible evolution. Moreover, it is extremely valuable
      in understanding of functioning of the living systems in unity of their organ and
      tissue structures. In the present paper, the organization of dermal glands and
      their possible eco-physiological role in the life of adult water mites are
      analyzed on the basis of the available data and original investigations from the
      point of view of fundamental functional-morphological approaches in the study of
      various groups of arthropods developed by Prof. Yu.S. Balashov.

PMID- 24455908
TI  - [Organization of studies of the "gnus" complex of bloodsucking dipterans
      (Diptera: Culicidae, Ceratopogonidae, Tabanidae) by Yu. S. Balashov].
AB  - The paper gives a historical account of investigations of mosquitoes, black flies
      and horseflies carried out by the staff of the Laboratory of Parasitology,
      Zoological Institute RAS, supervised by a corresponding member of the Russian
      Academy of Sciences, Prof Yu. S. Balashov, during 1979-1994. The research team of
      the laboratory explored the local fauna, relative abundance, seasonal dynamics,
      diurnal activity, longevity of a mass flight activity, annual fluctuations of the
      number, and age content of populations of various mosquito, black fly and
      horsefly species in the territory of Leningrad, Novgorod and Pskov Provinces.
      Attack peculiarities of various horse fly species were studied with the use of
      individual labeling.

PMID- 24455909
TI  - Estimation of malaria mortality of A District in India during 2010 by using three
      models.
AB  - There is no standard method for estimating annual malaria deaths in India. The
      degree of under-reporting in routine system is uncertain with a varied picture of
      10, 15, 25 and 200 times as found in different studies/models. During October
      2010 a community based cross-sectional survey was conducted by National Vector
      Borne Disease Control Programme (NVBDCP) in 32 villages of West Garo Hills
      district of Meghalaya. 'Gap filling', 'fever survey' and 'verbal autopsy' models,
      developed in NVBDCP were used on the data obtained from two surveys done
      simultaneously: 'fever survey' with 2 weeks recall period and 'death survey' with
      one year recall period. Inputs from demographic and epidemiological data of the
      district were also given. During 2010, the district has reported 32 malaria
      deaths. Degrees of under-reporting found in the study were 6.93, 7.53 and 12
      times in three models respectively. The first two models yielded closer
      estimates. But, verbal autopsy model gave inflated value as the method was
      unreliable for diagnosing malaria deaths. First two models, if found to be
      replicable, can be incorporated in NVBDCP activities to evaluate malaria control
      measures at district level. Verbal autopsy model may be used after concordance
      study in those districts where Pf malaria cases occur but no death is reported.

PMID- 24455910
TI  - Media scanning and verification system as a supplemental tool to disease outbreak
      detection & reporting at National Centre for Disease Control, Delhi.
AB  - Media scanning for unusual health events can efficiently supplement conventional
      communicable disease surveillance systems for early detection and response to
      outbreaks. There is a need to rapidly process and appropriately disseminate the
      media reports on unusual health events for timely action. Hence to address this
      need in India a Media Scanning & Verification Cell (MSVC) was established in July
      2008 at the National Centre for Disease Control, Delhi. MSVC is supervised by
      Epidemiologists working in Central Surveillance Unit of IDSP. This unique system
      monitors Global and National Media sources such as National and Regional print
      media, news on internet, news wires and websites, news channels and news shared
      by partners like Global Public Health Intelligence Network (GPHIN), Canada, WHO
      and other International and national agencies. The information is shared to the
      districts affected and District Surveillance Officer (DSO) and his team is
      expected to investigate and revert through the internet about the correctness and
      action taken. A mean number of 4 Media Alert reports are generated each day. A
      total of 1685 alerts were reported in a period between July 2008 to December
      2011. Of these 1241 (73.7%) were verified as real events and 183 (10.9%) were
      considered outbreaks by local health officials. Most events were captured through
      internet (57%) followed by the print media (24%). The most common disease events
      identified were food-borne and diarrhea (29.1%), dengue (10.68%), influenza &
      respiratory disease (8.1%) and malaria (7.4%). The sensitivity of MSVC to detect
      outbreaks was 14.8% with more than half of outbreaks detected before they were
      identified by the conventional surveillance system. It has proven to be a highly
      effective supplemental tool to official surveillance system in the detection of
      early warning signals and hence timely detection and management of public health
      threats in India.

PMID- 24455911
TI  - An epidemiological study on dog bite and its management in Bellary, Karnataka.
AB  - Animal bites are common childhood occurrences. Dog bites remain constant problem
      in our country because of the increasing dog population. To know the pattern of
      dog bites in children, the morbidity Pattern, the circumstances of dog bites,
      ascertain the first aid measures and Vaccination practiced by people after dog
      bites and the compliance with vaccination and adverse reactions due to
      vaccination, this cross sectional descriptive study was carried put on children
      who were dog bite victims attending VIMS hospital, Bellary during Feb 2011 to Nov
      2011. Out of 536 participants 71% were males and 29% were females. 35% of the
      participants belongs to 10-12 yr age group. Majority of the victims belongs to
      upper lower and lower class of socio economic group. 42% of children were bitten
      over lower limbs and 43.8% of the victims had some local treatment immediately.
      77% of the victims were received anti-rabies vaccine and only 11% of the dogs
      were vaccinated against rabies.

PMID- 24455912
TI  - Preliminary study on susceptibility status of Anopheles minimus Theobald and An.
      fluviatilis James (Diptera: Culicidae) to DDT and deltamethrin in Keonjhar
      district of Odisha, India.
AB  - This study was carried out to determine the susceptibility levels of An.
      fluviatilis and An. minimus to DDT (4%) and deltamethrin (0.05%) and to select
      the insecticide to be used for routine national malaria vector control programme
      based on the results of the susceptibility test. Susceptibility test was done as
      per standard WHO susceptibility tests using DDT(4%) and deltamethrin (0.05%) in
      the villages of Keonjhar Districts during 2009. The results indicate that An.
      fluviatilis showed 100% mortality to DDT (4%) and deltamethrin (0.05%) and An.
      minimus showed 96.2 per cent mortality to DDT (4%) and 100 per cent to
      deltamethrin (0.05%). An. fluviatilis and An. minimus have been incriminated as
      the major malaria vectors of Keonjhar district. Successful application of DDT and
      deltamethrin could reduce the vector load from this area with consequent malaria
      control as these two species are found to be highly susceptible to DDT and
      deltamethrin. Another study as per WHO methodology is further recommended to
      substantiate the result of this study.

PMID- 24455913
TI  - An epidemiological investigation of mumps outbreak in a slum of Kolkata.
AB  - An unexpected clustering of mumps cases were reported in a slum of Kolkata during
      early part of 2009. An epidemiological investigation was initiated with a view to
      assess the characteristics and determinants of the disease, and implications of
      such clustering of cases in a slum of Kolkata. Data were collected through house
      to house visit using predesigned schedule and epidemiological case sheet. The
      propagated outbreak existed for fifteen weeks yielding 104 clinical cases. On the
      whole, attack rate was 4.7%, the highest and lowest being in 6-10 years (11.68%)
      and above 15 years (0.94%), respectively. The parotid swelling was bilateral in
      92.3% of cases; fever was the most common general symptom, reportedly present in
      92.3% of study subjects. The overall mean duration of parotid swelling was 6.85
      +/- 1.89 days. Morbidity from mumps far exceeds the mortality rate. Improved
      ventilation of living rooms, personal & oral hygiene; isolation of cases,
      upgradation of routine immunization, better nutrition etc. were recommended at
      family & community level and introduction of MMR vaccine in National Immunization
      Schedule was suggested.

PMID- 24455914
TI  - An empirical malaria situation: a case study of Jamardihi PHC (new).
AB  - India accounts for 2/3rd confirmed cases of malaria reported in South-East Asia
      region in the world. Orissa accounted 130 malaria deaths in 2009, just ranked
      below Meghalaya. Angul district of Orissa has 3.09% of the state population. The
      ST population is 132,994 lakhs in the districts which is 11.66% of the district
      population. It has 87% of Pf prevalence and Pallalhada is one of the Blocks known
      for high Pf prevalence area. To access the malaria situation and its causes, a
      study was conducted in Bandhabhuin G.P. of Plallalhada Block. This paper
      presented the Malaria situation at Jamardihi PHC (New) area only. Total 120
      Households were selected as sample (60 Tribal and 60 Non tribal). Tools like
      Interview schedule and FGD were properly used. It was found that each unit has
      experienced Malaria episodes. Out of 120 households 13 Households had malaria
      cases at the time of survey. Mainly women and children are more vulnerable to
      malaria. People used to take treatment from both traditional methods as well as
      from hospital/PHC. It needs to strengthen the community process like Gaon Kalyana
      Samiti to fight against the fatal disease successfully.

PMID- 24455915
TI  - A study of bacteriological profile (aerobic) and antimicrobial susceptibility of
      community acquired pneumonia cases in the RIMS hospital.

PMID- 24455916
TI  - [Aerosol optical properties during different air-pollution episodes over
      Beijing].
AB  - Based on the 2005-2011 data from Aerosol Robotic Network (AERONET), this study
      conducted analysis on aerosol optical properties over Beijing during different
      air-pollution episodes (biomass burning, CNY firework, dust storm). The aerosol
      optical depth (AOD) showed notable increases in the air-pollution episodes while
      the AOD (at 440 nm) during dust storm was 4. 91, 4. 07 and 2.65 times higher as
      background, biomass burning and firework aerosols. AOD along with Angstrom
      exponent (alpha) can be used to determine the aerosol types. The dust aerosol had
      the highest AOD and the lowest alpha. The alpha value of firework (1.09) was
      smaller than biomass burning (1.21) and background (1.27), indicating that coarse
      particles were dominant in the former type. Higher AOD of burnings (than
      background) can be attributed to the optical extinction capability of black
      carbon aerosol. The single scattering albedo (SSA) was insensitive to wavelength.
      The SSA value of dust (0.934) was higher than background (0.878), biomass burning
      (0.921) and firework (0.905). Additionally, the extremely large SSA of burnings
      here maybe was caused by the aging smoke, hygroscopic growth and so on. The peak
      radius of aerosol volume size distributions were 0.1-0.2 microm and 2.24 -3.85
      microm in clear and polluted conditions. The value of volume concentration ratio
      between coarse and fine particles was in the order of clear background (1.04),
      biomass burning (1.10), CNY firework (1.91) and dust storm (4.96) episode.

PMID- 24455917
TI  - [Characteristics and source analysis of atmospheric aerosol ions over the Bohai
      Sea and the North Yellow Sea in Autumn].
AB  - The total suspended particulate (TSP) samples in aerosol were collected over the
      Bohai Sea (BS) and the North Yellow Sea (NYS) during Autumn 2010 to determine the
      concentration of main water-soluble cations (Na+, K+, NH4+, Mg2+, Ca2+) and
      anions [Cl-, NO3-, SO4(2-), CH3SO3(-) (MSA)] by ion chromatography. Main sources
      of these ions were discussed by combined enrichment factors and correlation
      analyses. The concentration of total water-soluble ions ranged from 30.9 microg x
      m(-3) to 58.8 microg x m(-3) over the BS and from 5.03 microg x m(-3) to 39.8
      microg x m(-3) over the NYS, respectively, with averages of (40.3 +/- 10.1)
      microg x m(-3) and (19.2 +/- 11.8) microg x m(-3). Analytical results showed that
      the level of the second ions (nss-SO4(2-), NO3(-) and NH4+) were the highest,
      accounting for 87.5% and 62.8% of total identified ions over the BS and the NYS.
      Enrichment factors showed that Mg2+ and Cl-mainly came from oceanic sources and
      the main source of K+ was crust. The analysis of sulfate source showed that sea
      salt sulfates over the BS and the NYS accounted for 1.2% and 12.1% of the total
      sulfate and contributions of biogenic sulfates to nss-SO4(2-) were 5.0% and
      14.6%, respectively, indicating that human activities were the main source of
      sulfate in aerosol in the study area.

PMID- 24455918
TI  - [Spatial distribution characteristics of carbonaceous aerosol during summer in
      Beibu Gulf Zone, China].
AB  - Daily (24-h average) PM2.5 samples were collected simultaneously at urban and
      suburban sites of nine cities (Nanning, Qinzhou, Fangchenggang, Beihai,
      Zhanjiang, Maoming, Haikou, Yangpu and Dongfang) in Beibu Gulf Zone during August
      2009. All samples were analyzed for organic and elemental carbon (OC and EC)
      analyses by the thermal/optical reflectance following IMPROVE protocol.
      Characteristics of OC and EC concentration levels, spatial distribution, and the
      possible sources were discussed. The average concentrations of PM2.5, OC and EC
      in Beibu Gulf zone were (38.4 +/- 17.7), (9.2 +/- 2.6) and (1.9 +/- 1.1) microg x
      m(-3), respectively. The total carbonaceous aerosol (TCA) accounted for over
      56.8% of PM2.5. OC mainly came from biomass burning and secondary organic carbon
      (SOC), while motor exhaust and industrial emissions were the primary source of EC
      during summer in Beibu Gulf Zone.

PMID- 24455919
TI  - [Study on the in-situ measurement of greenhouse gas by an improved FTIR].
AB  - The real-time, automatic, highly accurate and efficient system for measuring the
      mixing ratios of CO2, CH4, CO and N2O has been developed by combining the
      commercial FTIR system (Wollongong University) with an auto-sampling system and a
      working standard module. Based on the tests conducted, the FTIR showed the high
      precision and a relatively low accuracy associated with its poor determination of
      correction factors. The absolute error of the mixing ratio of CO was above 38.8 x
      10(-9), suggesting that FTIR alone could not meet the requirement for the real
      time measurement. Using the working standard gases to adjust results from the
      FTIR significantly improved the accuracy of measurements. For both static and
      dynamic conditions, the discrepancies between the measured results and the real
      values were below 0.11 x 10(-6), 1.8 x 10(-9), 0.15 x 10(-9) and 0.5 x 10(-9) for
      CO2, CH4, N2O and CO respectively, meeting the requirements for the atmospheric
      real-time measurements. During 6 days in-situ measurements of greenhouse gas
      outside the lab, the precision of target gas can reach 0.05 x 10(-6), 0.2 x 10(
      9), 0.07 x 10(-9), 0.5 x 10(-9) for CO2, CH4, N2O, CO, and inaccuracy can be 0.09
      x 10(-6), 0.4 x 10(-9), 0.14 x 10(-9), 0.5 x 10(-9), respectively.

PMID- 24455920
TI  - [Distribution of CH4 in the suburb of Changsha City, China].
AB  - To study the variation of atmospheric CH4 concentration in the Yangtze River
      region, air samples which collected weekly using flasks from the suburb of
      Changsha City from 2007 to 2011 and the CH4 concentration was measured by gas
      chromatography. CH4 concentrations were analyzed combined with ground
      meteorological elements and backward trajectories to explore the CH4
      concentration variations with source-sink relationships. The results showed that
      during the observation period, the annual mean concentration of CH4 was in the
      range 2012 x 10(-9) - 2075 x 10(-9) (volume mixing ratio, the same below). The
      difference between the maximum and minimum monthly mean of CH4 concentrations was
      152 x 10(-9), with the highest concentration observed in autumn and the lowest in
      spring. Analysis of the surface wind showed that the concentration of CH4 was
      controlled by northwest wind and southerly winds alternately, and the
      contribution rate was 41.1% and 20.4%, respectively. Surface winds causing CH4
      concentration uplift included W-WNW-NW in all four seasons, ESE-SE in summer and
      S in winter; while S in spring and summer have resulted in the decrease of CH4
      concentration. Analysis of the air mass transport showed that the concentration
      of CH4 in the suburb of Changsha was significantly contributed by air masses from
      rice-producing areas in summer and high energy consumption areas in winter, and
      was cleared by air masses of long-distance transport from southern district.

PMID- 24455921
TI  - [Chemical composition of n-alkanes in wheat straw and smoke].
AB  - Straw of six wheat species was burned under flaming and smoldering conditions.
      Chemical compositions of n-alkanes in the straw and its smoke were measured with
      GC/MS. The results showed, the main compounds in all samples were C16 to C33, and
      the total amounts of n-alkanes in the straw were between 19.6 and 62.3 mg x kg(
      1), with a mean value of 36.0 mg x kg(-1). Moreover, the ratios of the contents
      of n-alkanes with low carbon number (< C23) to the total n-alkanes varied from
      1.4% to 31.6%. The C27/C29 values in straws ranged from 20.2% to 47.4% with an
      average of 33.7%, and the C31/C29 values ranged from 22.9% to 48.1% with a mean
      value of 32.7%. In the flaming smoke, the total contents were 764.2 to 5 304.1 mg
      x kg(-1), with a mean value of 2 854.2 mg x kg(-1). And the contribution of the
      compounds with low carbon number to the total contents was 2.0% to 19.4%, the
      mean of which was 7.1%. Furthermore, the C27/C29 ratios changed from 10.0% to
      31.6% with an average of 20.2%, and the C31/C29 values ranged from 47.1% to 98.9%
      with a mean of 71.2%. In the smoldering smoke, the total contents were in the
      range of 5 126 to 15 898 mg x kg(-1), and the mean value was 9 220.8 mg kg(-1).
      The ratios of the content of n-alkanes with low carbon number to the total n
      alkanes varied from 1.9% to 13.0%, and the average value was 5.5%. In addition,
      the C27/C29 values ranged from 8.6% to 23.0% with a mean of 13.8%, and C31/C29
      ratios varied from 42.5% to 90.2% with an average of 62.2%. In both the straw and
      the smoke, n-alkanes showed unimodal distribution with a peak at C29. The
      compounds with high carbon number (> C21) in all samples had evident odd to even
      carbon number predominance. The carbon predominance index (CPI) for the straw
      ranged from 4.0 to 33.6 with a mean value of 19. 2, and the corresponding average
      carbon chain length (ACL) varied from 25.2 to 29.0 with a mean of 28.0. The CPI
      for flaming smoke was between 4.4 and 27.1 with a mean value of 12.4, and the
      corresponding ACL varied from 27.6 to 29.4 with an average value of 28.8. The CPI
      values for smoldering smoke ranged from 5.5 to 29.6 with a mean of 18.0, and the
      ACL was from 28.0 to 29.5 with an average value of 28.9. In short, there were
      visible differentiations among the chemical compositions of n-alkanes in wheat
      straw and its smoke, which are helpful for identifying the organic contaminants
      in ambient aerosol from wheat straw burning.

PMID- 24455922
TI  - [Degradation of the absorbed methyl mercaptan by persulfate in alkaline
      solution].
AB  - Methyl mercaptan (CH3SH) is considered to be an important contributor to odors.
      It is a toxic, corrosive and acid gas. The absorption of CH3SH by alkaline
      solution is one of the most widely used processes, but the remained solution
      should be further treated. The degradation of dissolved CH3S- by persulfate (PS)
      oxidation has not been reported. CH3SH is absorbed in alkaline solution and
      degraded by PS oxidation using a recycling continuous system for absorption and
      degradation. The stability of PS under alkaline conditions is discussed. The
      influence of different reaction conditions on the absorption rate and degradation
      rate is also studied. It was observed that PS was relatively stability under
      alkaline conditions and the dissolved CH3S- could be degraded effectively by PS.
      The absorption rate of CH3SH first increased and then decreased with the
      increasing concentration of PS. The degradation rate of CH3S- increased with the
      increasing concentration of PS. It was also observed that the efficiency between
      absorption and degradation had been significantly increased with the increasing
      of pH. In the conditions of pH = 12, fixed CH3SH concentration of 80 mg x m(-3)
      with a fixed gas flow rate of 1.5 L x min(-1), 1.4 g x L(-1) PS, 90% of the
      dissolved CH3S- can be degraded.

PMID- 24455923
TI  - [Emissions of greenhouse gas and ammonia from the full process of sewage sludge
      composting and land application of compost].
AB  - There is a great uncertainty of greenhouse gas (GHG) reduction and nitrogen
      conservation from the full process of sludge composting and land application of
      compost in China due to the lack of emission data of GHG such as N2O and CH4 and
      ammonia (NH3). The purpose of this study is to get emission characteristics of
      GHGs and NH3 from the full process with on-site observation. Results showed that
      the total GHG emission factor from full process of the turning windrow (TW)
      system (eCO2/dry sludge, 196.21 kg x t(-1)) was 1.61 times higher of that from
      the ATP system. Among the full process, N2O was mostly from the land application
      of compost, whereas CH4 mainly resulted from the sludge composting. In the sludge
      composting of ATP, the GHG emission equivalence of the ATP (eCO2/dry sludge,
      12.47 kg x t(-1) was much lower than that of the TW (eCO2/dry sludge, 86.84 kg x
      t(-1)). The total NH3 emission factor of the TW (NH3/dry sludge, 6.86 kg x t(-1))
      was slightly higher than that of the ATP (NH3/dry sludge, 6.63 kg x t(-1)). NH3
      was the major contributor of nitrogen loss in the full process. During the
      composting, the nitrogen loss as NH3 from both TW and ATP was nearly the same as
      30% of TN loss from raw materials, and the N and C loss caused by N2O and CH4
      were negligible. These results clearly showed that the ATP was a kind of
      environmentally friendly composting technology.

PMID- 24455924
TI  - [Distribution and physicochemical properties of aquatic colloids in the Yangtze
      estuarine and coastal ecosystem].
AB  - Cross-flow ultrafiltration (CFUF) technique was applied for isolating colloids
      from waters in the Yangtze estuarine and coastal ecosystem. The stability and
      physicochemical properties of colloids were analyzed quantitatively. Colloidal
      size and Zeta-potential at XP and WSK station decreased with the increasing pH,
      and reached the point of zero charge at pH < 2 and pH 3.8, respectively. The
      colloidal organic carbon (COC) concentration in the collected samples was 7.7
      35.7 micromol x L(-1), occupying 7.1% -41.7% of the total dissolved organic
      carbon (DOC). Three-dimensional excitation/emission matrix fluorescence
      spectroscopy (3DEEM) was used to analyze the samples and the results showed
      tryptophan-like fluorescence peaks, UV fulvic-like fluorescence peaks and humic
      like fluorescence peaks. Concentrations of colloidal Na, Mg, K, Ca, Co, Cr, Cu,
      Fe, Li, Mn and Ni accounted for 0.33%, 5.7%, 0.975%, 1%, 7.2%, 7%, 11.9%, 15.7%,
      5.5%, 10.5% and 11.3% of the dissolved phase in average, and the binding capacity
      of Co, Cr, Cu, Fe, Li, Mn, Ni with COC was generally higher than that of Na, Mg,
      K, Ca. There were significant correlations between colloidal size and salinity,
      between DOC and salinity, and between UOC and salinity, but no linear
      relationship between COC and salinity was found. The total concentration of trace
      metals (Co, Cr, Cu, Fe, Li, Mn, Ni) and COC showed a linear relationship.

PMID- 24455925
TI  - [Spatial distribution and ecological risk assessment of heavy metals in the
      estuaries surface sediments from the Haihe River Basin].
AB  - It is well known that the rivers in the Haihe River Basin have been seriously
      polluted. However, what is the present condition of the estuary pollution and how
      the polluted inland rivers affect the estuary areas are not clear. 10 main
      estuaries of the Haihe River Basin were selected to measure the contents of
      typical heavy metals (Pb, Cu, Zn, Cd, Cr and Ni) in the surface sediments and to
      analyze the spatial distribution of these heavy metals. The potential ecological
      risk index was used to assess the ecological risk of the six heavy metals in the
      estuaries. The results showed that the contents of Pb, Cu, Zn, Cd, Cr and Ni in
      the surface sediments of the 10 estuaries were all higher than their background
      values in the main local soil types and the contents of Cu, Ni and Pb were 2.3
      2.6 times as high as their background values, which indicated that the estuaries
      were contaminated by the six heavy metals. The results also indicated that the
      contents of the six heavy metals in surface sediment varied from one estuary to
      another. The four heavy metals of Cr, Cu, Ni and Zn had bigger spatial
      differences than Pb and Cd in the contents in sediment from different estuaries.
      The contents of Cr, Cu, Ni and Zn in sediment were higher in the estuaries of the
      Yongdingxin River, Ziyaxin River and Beipai River than those in the other
      estuaries, and there were significant correlations between each other (R(Cu-Zn) =
      0.891, R(Cu-Cr) = 0.927, R(Cu-Ni) = 0.964, R(Zn-Cr) = 0.842, R(Zn-Ni) = 0.939,
      and R(Cr-Ni) = 0.879, P < 0.01), which indicated that they possibly came from the
      same sources. Moreover, the contents of Cr, Cu, Ni and Zn in sediment also had
      significant correlations with the populations of sub-river basins with
      correlation coefficients of 0.855, 0.806, 0.867 and 0.855 (P < 0.01),
      respectively. The contents of Cd and Pb had smaller spatial differences in
      sediment from different estuaries than the other heavy metals, with the values
      ranged 23.3-95.8 mg x kg(-1) and 0.051-0.200 mg x kg(-1). Contents of the two
      heavy metals had no significant correlation with the other heavy metals or with
      the populations of sub-river basins, indicating that Cd and Pb had little
      connection with the in-land polluted sources. The results of ecological risk
      assessment showed that estuaries of the Haihe River Basin had the potential
      ecological risk at lower levels (RI were 33.7-116) and the most important
      contaminating element was Cd with a middle-level potential ecological risk (Er(i)
      were 18.0-48.9).

PMID- 24455926
TI  - [Distribution of perfluorooctanesulfonate and perfluorooctanoate in water and the
      sediment in Fenhe River, Shanxi Provice].
AB  - This study investigated the distribution of Perfluorooctanesulfonate (PFOS) and
      Perfluorooctanoate (PFOA) in Fenhe River. A solid phase extraction (SPE)
      pretreatment method was used together with liquid chromatography tandem mass
      spectrometry (LC-MS/MS) to analyze the concentrations of PFOS and PFOA in Fenhe
      River, which were found to be in the ranges of 3.54-16.23 ng x L(-1) and 2.49
      4.79 ng x L(-1) in the water phase, and in the ranges of 7.77-51.22 ng x g(-1)
      and 1.94-3.54 ng x g(-1) in the sediment, respectively. In water samples, the
      PFOS levels showed an increasing trend from the upstream to the downstream of the
      river, while the PFOA levels were similar among all the samples. In sediment
      samples, the increasing tendency of PFOS concentrations was not as obvious as in
      water samples, and the PFOA levels were again similar. Besides, the partitioning
      of PFOS between the water phase and the sediment was related to the content of
      organic carbon in the sediment. However, there was no significant correlation
      between PFOA partitioning and the organic carbon content.

PMID- 24455927
TI  - [Analysis on nitrogen and phosphorus loading of non-point sources in Shiqiao
      river watershed based on L-THIA model].
AB  - Based on the Long-term Hydrological Impact Assessment (L-THIA) model, the effect
      of land use and rainfall change on nitrogen and phosphorus loading of non-point
      sources in Shiqiao river watershed was analyzed. The parameters in L-THIA model
      were revised according to the data recorded in the scene of runoff plots, which
      were set up in the watershed. The results showed that the distribution of areas
      with high pollution load was mainly concentrated in agricultural land and urban
      land. Agricultural land was the biggest contributor to nitrogen and phosphorus
      load. From 1995 to 2010, the load of major pollutants, namely TN and TP, showed
      an obviously increasing trend with increase rates of 17.91% and 25.30%,
      respectively. With the urbanization in the watershed, urban land increased
      rapidly and its area proportion reached 43.94%. The contribution of urban land to
      nitrogen and phosphorus load was over 40% in 2010. This was the main reason why
      pollution load still increased obviously while the agricultural land decreased
      greatly in the past 15 years. The rainfall occurred in the watershed was mainly
      concentrated in the flood season, so the nitrogen and phosphorus load of the
      flood season was far higher than that of the non-flood season and the proportion
      accounting for the whole year was over 85%. Pearson regression analysis between
      pollution load and the frequency of different patterns of rainfall demonstrated
      that rainfall exceeding 20 mm in a day was the main rainfall type causing non
      point source pollution.

PMID- 24455928
TI  - [Pollutant source apportionment of combined sewer overflows using chemical mass
      balance method].
AB  - Pollutant characteristics of surface runoff, sanitary sewage and sewer deposits
      from a combined sewer system in Shanghai were studied. It was confirmed that the
      content of Zn, NH4(+) -N, P, respectively in surface runoff, sanitary sewage and
      sewer deposits was specific and relatively stable based on contrasting pollutant
      characteristics of different sources. Three non-dimensional parameters-Zn/P,
      NH4(+) -N/Zn, P/K were proposed as characteristic index for surface runoff,
      sanitary sewage and sewer deposits. In order to find sources of pollutants in
      CSO, the application of chemical mass balance method was discussed: the average
      contributions to CSO were 42.8% for surface runoff, 12.2% for sanitary sewage,
      23.8% for sewer deposits, and the results basically reflected the composition of
      CSO pollution. The research method and results can provide guidance for pollutant
      source apportionment of combined sewer overflows.

PMID- 24455929
TI  - [Simulated study of algal fatty acid degradation in hypoxia seawater-sediment
      interface along China coastal area].
AB  - Series of laboratory incubation experiments were conducted to simulate
      degradation of organic matter in sediment-seawater interface in hypoxia
      enviroments along China coastal area. Under four different redox conditions
      (oxygen saturation: 100%, 50%, 25% and 0%), degradations of seveal biomarkers
      originated from Skeletonema costatum, a typical red tide alage along China
      coastal area were tracked. By analyzing concentrations of four fatty acid
      biomarkers [14:0, 16:0, 16:1(7) and 20:5] obtained at various sampling time,
      results showed that their concentrations decreased significantly after 2-3 weeks'
      incubation. Then, their concentrations changed very slowly or very little.
      However, degradation of the four fatty acids varied dramatically in different
      incubation systems. Fatty acids 14:0, 16:1(7) and 20:5 were degraded completely
      in all incubation systems after two-month incubation, but 25% to 35% of 16:0 was
      reserved in the systems. Based on multi-G model, degradations of the four fatty
      acids were quantively described. The results indicated that all four fatty acids
      had fast-degraded and slow-degraded fractions. Their degradation rate constants
      (k(av)) ranged from 0.079 to 0.84 d(-1). The fastest degradation of 14:0 and 16:1
      (7) occurred under 25% oxygen concentrations. For these two compounds, in the
      fastest degradation system, their k(av), values were 2.3 folds and 1.7 folds
      higher than those in the slowest degradation system [50% oxygen saturation for
      14:0 and 100% oxygen saturation for 16:1(7)] respectively. The 16:0 was degraded
      fastest under the anoxic condition and slowest under the 50% oxygen saturation.
      The ratio of the two k(av)s was 2.1. The k(av)s of 20:5 had a positive
      relationship with oxygen saturations. Results of this study suggested that
      besides oxgen saturations, structure and features of organic compounds, roles of
      microbe in the envrioments and etc. might affect degradations of fatty acids in
      S. costatum in hypoxia sediment-seawater interface along China coastal area.

PMID- 24455930
TI  - [Influence of two different species of aquatic plant communities on the
      concentration of various nitrogen forms in sediment of Lake Taihu].
AB  - To investigate the spatial distribution of nitrogen in the sediment from both
      internal and external sites of Potamogeton malaianus and Limnanthemun nymphoides
      communities, levels of various forms of nitrogen were quantified in sediment
      samples collected from Gonghu Bay, the southern region and the intermediate area
      between East and West mountains of Lake Taihu in June 2012. The results showed
      that: (1) Within the algae-type region in Gonghu Bay, the contents of organic
      (Org-N) and total nitrogen (TN) in the internal sediment (0-25 cm) from P.
      malaianus communities were higher than those of the external sediment, by 38.06%
      and 25.65%, respectively. (2) In the non-algal region, the contents of TN, Org-N,
      NH4(+)-N and NO3(-) -N in the internal sediments from P. malaianus communities
      were lower by 43.29%, 50.78%, 7.09% and 10.86% compared to those in the external
      sediments; for L. nymphoides communities, the contents of TN, Org-N, NH4(+) -N
      and NO3(-) -N in the external sediments were lower by 4.65%, 4.63%, 5.01% and
      2.76% compared to the internal sediments. These values suggested that the
      promotion in reducing sedimentary nitrogen was more effective by the P. malaianus
      community than by the L. nymphoides community. (3) A significant positive
      correlation (P < 0.05, n = 24) was found between pH and TN within the external
      sediments and between pH and NO3(-) -N within the internal sediments (P < 0.05, n
      = 24), while a significant negative correlation (P < 0.05, n = 24) was found
      between pH and NH4(+)-N of both aquatic plant communities. The redox potential
      (Eh) was also found to be significantly positively correlated with TN in both the
      internal and external sediments of P. malaianus communities (GMN, P < 0.01, R =
      0.922 8 * *; NMN, P < 0.01, R = 0.827 7 * *; GMW, P < 0.05, R = 0.748 9 *; NMW, P
      < 0.05, R = 0.663 7 *). It is therefore concluded that the presence of aquatic
      plant communities could impact the physical and chemical properties of the
      sediments.

PMID- 24455931
TI  - [Study on removal rule of endosulfan in surface flow constructed wetland].
AB  - Endosulfan is a kind of widespread organochlorine pollutant in the environment.
      The removal rule of three different concentrations of endosulfan in different
      parts of a surface flow constructed wetland was investigated. The concentrations
      of endosulfan in water, plants, non-rhizosphere sediments and rhizosphere
      sediments were determined by the Soxhlet extraction-GC method. The results showed
      that constructed wetland was efficient in endosulfan removal. The removal rate of
      endousulfan in water, non-rhizosphere sediments and rhizosphere sediments was
      87.9%, 63.0% and 70.9%, respectively. In this system, alpha-endosulfan was
      removed faster than beta-endosulfan and the metabolite accumulated was mainly
      endosulfan sulfate. The adsorption of sediments played an important role in the
      removal of endosulfan. About 80.0% of endosulfan in water could be adsorbed by
      sediments within three days. The removal rate of endosulfan could be enhanced by
      plants. Because of the effect of plants, the average removal rate of endosulfan
      in rhizosphere sediments was 7.9% higher than that in non-rhizosphere sediments.

PMID- 24455932
TI  - [Accumulation and transformation of different arsenic species in nonaxenic
      Dunaliella salina].
AB  - Algae and bacteria are usually symbiotic in the environment. The algae-bacteria
      consortia have a good prospect in the remediation of polluted environment. In
      this study, we isolated a bacterium from nonaxenic Dunaliella salina and
      identified it as Bacillus solisalsi using 16S rRNA sequence analysis. The uptake,
      adsorption and transformation of As by the nonaxenic D. salina and the
      concentration and speciation of As in the culture solution were determined after
      13 days exposure to various concentrations of As(III) and As( V). The results
      showed that D. salina had a high As tolerance. When the algae was exposed to 250
      micromol x L(-1) and 500 micromol x L(-1) arsenite, As accumulations were 3.78 g
      x kg(-1) and 4.56 g x kg(-1), respectively, but the As removal from the solution
      was 7.9% - 8.3%. B. solisalsi did not show a strong ability to clean up As either
      (6.1%-19.9% removal rate). The consortia of D. salina and B. solisalsi showed a
      higher As removal ability. Moreover, 0.99-2.79 g x kg(-1) and 1.22-3.46 g x kg(
      1) As were absorbed when exposed to 25-100 micromol x L(-1) and 25-500 micromol x
      L(-1) As(III) and As(V), respectively. More than 54.3% of As were taken away by
      the consortia from the solution under the exposure of 25-100 micromol x L(-1)
      As(III) and As(V). Various pathways of As detoxification were identified for the
      nonaxenic D. salina: As(III) oxidation, As(V) reduction, As(III) methylation, and
      efflux of As from cells.

PMID- 24455933
TI  - [Evaluation of in situ capping with lanthanum-modified zeolite to control
      phosphate and ammonium release from sediments in heavily polluted river].
AB  - The efficiency and mechanism of sediment capping with an active barrier system
      (ABS) using lanthanum-modified zeolite (LaMZ) to simultaneously prevent phosphate
      and ammonium release from sediments in heavily polluted river under low dissolved
      oxygen conditions were investigated using batch and sediment incubation
      experiments. The adsorption kinetics of phosphate and ammonium on LaMZ followed a
      pseudo-second-order model. The equilibrium adsorption data of phosphate on LaMZ
      could be described by the Langmuir isotherm model. The equilibrium adsorption
      data of ammonium on LaMZ could be described by the Langmuir, Freundlich and
      Dubinin-Radushkevich (D-R) isotherm models. The mechanisms for phosphate
      adsorption onto LaMZ at pH 7 included ligand exchange, Lewis acid-base
      interaction and electrostatic attraction. The mechanism for ammonium adsorption
      onto LaMZ at pH 7 was cation exchange. The fluxes of phosphate and ammonium from
      the sediment to the overlying water were significantly reduced by the ABS using
      LaMZ under low dissolved oxygen conditions. Higher LaMZ dosage was found to be
      favorable for the prevention of ammonium release from the sediments using the
      ABS. Sequential extraction of phosphorus from phosphate-adsorbed LaMZ indicated
      that most of phosphate immobilized by the ABS using LaMZ was stable and unlikely
      to be released under low dissolved oxygen conditions. Results of this work
      indicate that LaMZ is a suitable capping material for preventing phosphate and
      ammonium release from sediments in heavily polluted river under low dissolved
      oxygen conditions.

PMID- 24455934
TI  - [Effects of invertebrate bioturbation on vertical hydraulic conductivity of
      streambed for a river].
AB  - Streambed hydraulic conductivity is a key factor influencing water exchange
      between surface water and groundwater. However, the streambed invertebrate
      bioturbation has a great effect on the hydraulic conductivity. In order to
      determine the impact of invertebrate bioturbation on streambed hydraulic
      conductivity, the investigation of invertebrate bioturbation and in-situ test of
      vertical hydraulic conductivity of streambed are simultaneously conducted at five
      points along the main stream of the Weihe River. Firstly, correlation between the
      streambed vertical hydraulic conductivity and grain size distribution is
      analyzed. Secondly, type and density of the invertebrate and their correlation to
      hydraulic conductivity are determined. Finally, the effect of invertebrate
      bioturbation on the streambed hydraulic conductivity is illustrated. The results
      show that the vertical hydraulic conductivity and biological density of
      invertebrate are 18.479 m x d(-1) and 139 ind x m(-2), respectively for the
      Caotan site, where sediment composition with a large amount of sand and gravel
      particles. For Meixian site, the sediment constitutes a large amount of silt and
      clay particles, in which the vertical hydraulic conductivity and biological
      density of invertebrate are 2.807 m x d(-1) and 2 742 ind x m(-2) respectively.
      Besides, for the low permeability of four sites (Meixian, Xianyang, Lintong and
      Huaxian), grain size particles are similar while the vertical hydraulic
      conductivity and biological density of invertebrate are significantly different
      from one site to another. However, for each site, the vertical hydraulic
      conductivity closely related to biological density of invertebrate, the Pearson
      correlation coefficient is 0.987. It can be concluded that both grain size
      particles and invertebrate bioturbation influence sediment permeability. For
      example, higher values of streambed hydraulic conductivity from strong
      permeability site mainly due to the large amount of large-size particles and that
      from low permeability site is the main results from higher biological density of
      invertebrate. Large amount of grain size particles can expand pore space and the
      invertebrate bioturbation can destroy clogging sediment and enhance sediment
      permeability.

PMID- 24455935
TI  - [Formation of disinfection by-products by Microcystis aeruginosa intracellular
      organic matter: comparison between chlorination and bromination].
AB  - In order to illustrate the effects of released algal organic matter in
      cyanobacteria blooms on raw water quality and water treatment process,
      intracellular organic matter (IOM) of Microcystis aeruginosa, which is the
      dominant species in cyanobacteria blooms, was chosen as a precursor and
      characterized. In addition, the transformation of IOM and the formation of
      disinfection byproducts were evaluated at different pH of 6.5, 7.1 and 8.4 after
      chlorination or bromination, with subsequent correlation analysis. The results
      indicated that IOM was primarily composed of macromolecular matter, i. e. , the
      species with relative molecular weight of > 30 x 10(3), constituting 68.8% of
      dissolved organic carbon (DOC). Fluorescence excitation-emission matrix indicated
      that IOM was mainly composed of aromatic protein-like matter with an intensity of
      92.6 AU x L x mg(-1). After reaction with chlorine or bromine, the intensity of
      aromatic protein-like peaks decreased sharply by 76.6% - 93.3%, and its reduction
      correlated well with the formation of trihalomethane (THMs, R2 = 0.81) and
      haloacetic acid (HAAs, R2 = 0.77). The formation of THMs and HAAs increased with
      the increase in pH. Compared with chlorine, bromine formed more THMs and HAAs,
      and tended to form highly halogenated HAAs. However, with increasing pH, the
      reactivity with IOM between chlorine and bromine was closer, i.e, k(OBr
      IOM)/k(OCl-(IOM) < k(HOBr-IOM/k(HOCl-IOM).

PMID- 24455936
TI  - [Effect of natural organic matter on coagulation efficiency and characterization
      of the flocs formed].
AB  - Coagulation is an efficient way to remove the natural organic matter in water.
      Our works primarily focused on the effect of natural organic matter on
      coagulation and the properties of the flocs formed. PACl25 was used as the
      coagulant in this research to simulate the process of coagulation, and typical
      substance of NOM, humic acid and citric acid were used to prepare the model
      water. The impact of NOM on the size, fractal dimension, Zeta potential of the
      flocs and residual aluminum in solution was explored. The experiment results
      showed that as the concentration of humic acid and citric acid increased in the
      experimental range, the size and growth velocity of flocs, Zeta potential and
      fractal dimension showed a tendency of decrease (when the concentration of humic
      acid increased from 0 mg x L(-1) to 10 mg x L(-1), citric acid increased from 0
      micromol x L(-1) to 7 micromol x L(-1), the size of flocs before breakage was
      decreased by 34.2% and 53.1%, respectively, the Zeta potential decreased from
      about 10 mV to approximately -10 mV and -2.5 mV, the growth velocity of the flocs
      was decreased by 42.6% and 77.5%, and the fractal dimension declined by 0.08 and
      0.094), which showed the occupying of the floc surface by NOM resulted in the
      decrease of its activity and compactivity. However, the residual aluminum was not
      affected by the decrease of coagulation efficiency.

PMID- 24455937
TI  - [DOM membrane fouling and effects on rejection behaviors of NF membranes].
AB  - This work investigated membrane fouling caused by two kinds of dissolved organic
      matters (DOMs), i. e., Qingcaosha (QCS) DOM and Taihu lake (TH) DOM, and the
      effects on the rejection behaviors of two different nanofiltration (NF)
      membranes, i. e., HL and ESNA1-K, using carbamazepine (CBZ) as a molecular
      indicator. The results showed that severe membrane fouling occurred in the
      presence of DOM. And the CBZ removal rate was associated with the properties and
      characteristics of the organic matters and the membranes. It was found that the
      hydrophobicity of adhered DOM cake layer was responsible for the flux decline and
      the influence of CBZ removal. QCS DOM increased the retention of CBZ, while TH
      DOM decreased the rejection rate of CBZ by both membranes tested. DOMs at medium
      relative molecular weight (M(r) 1 500-10 000) could adhere closely to NF
      membranes to form cake layer, thus changed the hydrophobicity of the membranes.
      DOMs at low molecular weight could enter the membrane pores reducing the M(r),
      which influenced the CBZ removal and resulted in membrane fouling. The experiment
      also showed that DOM of TH contained more hydrophobic organic matters than that
      of QCS, the adhesion free energy and cohesion free energy of which was more
      negative, and the resulting membrane fouling and membrane flux decline were more
      severe.

PMID- 24455938
TI  - [Removal of Hg in wastewater by zero-valent iron].
AB  - Kinetic characteristics of mercury ion (Hg2+) removal in wastewater by zero
      valent iron (ZVI) and the influence factors were studied, and the reaction
      mechanism of ZVI and Hg2+ was preliminarily discussed. The removal rate of Hg2+
      in wastewater reached 94.5% under the optimal removal conditions, i. e. the
      initial concentration of Hg2+ was 0.10 mg x L(-1), the initial pH was 5, the ZVI
      dosage was 0.050 g, and the temperature was 25 degrees C. There was a rapid
      removal process for Hg2+ in wastewater by ZVI, which could be described by the
      pseudo first-order reaction kinetic equation, and the rate constant was 0.010
      min(-1). The removal mechanism of Hg2+ may mainly be attributed to the oxidation
      reduction of ZVI, and the adsorption and flocculation precipitation of iron
      oxides and hydroxides. However, the passivation of FeOOH and Fe2O3-Fe3O4 on ZVI
      surface may be the main reason for the decrease in the removal rate of Hg2+.
      Humic acid (HA) in wastewater could not only form Fe-HA complex with the Fe2+ and
      Fe3+ produced by ZVI reduction, which increased the ratio of soluble iron and
      relieved ZVI passivation, but also stabilize fine iron oxide and iron hydroxide
      colloid, and thus enhance the adsorption of Hg2+ in wastewater.

PMID- 24455939
TI  - [Catalytic dechlorination of 2, 4-D in aqueous solution by Fe3O4-stabilized
      nanoscale Pd/Fe].
AB  - Fe3O4-stabilized nanoscale Pd/Fe was used to dechlorinate 2,4-D in aqueous
      solution and achieved high dechlorination efficiency. The Fe3O4 dosage, pH, Pd
      loading, temperature and stirring rate were important factors for dechlorination
      of 2,4-D. The removal rate of 2,4-D increased with the increase of Fe3O4, dosage,
      and it reached 93.5% after 210 min when the Fe3O4 dosage was 4.0 g x L(-1), while
      only 47.3% 2,4-D was transformed using bare nanoscale Pd/Fe. Low pH enhanced
      dechlorination and 2,4-D was almost completely dechlorinated within 110 min when
      the pH ranged from 2.6 to 4.1. The dechlorination efficiency was significantly
      influenced by Pd loading. After 210 min, the different Pd loading, 0.25%, 0.50%
      and 0.75%, resulted in 2,4-D reduction efficiency of 51.4%, 93.5% and 99.9%,
      respectively. The removal rate was higher than 90.0% after 210 min in the
      temperature range of 16.5 degrees C to 30.0 degrees C, while it decreased
      significantly when the temperature rose to 35.0 and 40.0 degrees C. The
      dechlorination efficiency was improved with the increasing stirring rate. Fe3O4
      prevented the aggregation of nanoscale Pd/Fe particles. In addition, Fe3O4 acted
      as a medium to promote the electron transfer from Fe(0) to H+ and 2,4-D, and thus
      enhanced the reductive dechlorination of 2,4-D.

PMID- 24455940
TI  - [Comparative study on adsorption behaviors of natural organic matter by powered
      activated carbons with different particle sizes].
AB  - The effect of powered activated carbon (PAC) particle size in the range of 10-100
      microm on the adsorption of natural organic matter (NOM) in micro-polluted water
      was investigated, and the adsorption fractionation characteristics in terms of
      relative molecular mass distribution changes were evaluated. Three PACs with
      different median particle diameters were obtained through grinding and sieving of
      a commercial PAC product: PAC-1 (19 microm), PAC-2 (46 microm), and PAC-3 (76
      microm). The adsorption results showed that with the decrease of particle size,
      the adsorption properties (both adsorption capacity and adsorption rate) of PAC
      for NOM in both simulated and real micro-polluted water were significantly
      enhanced. The faster adsorption rate of PAC with smaller particles was attributed
      to its more available adsorption sites and shorter diffusion distance for
      adsorbate molecules. The larger adsorption capacity of smaller particle PACs was
      mainly due to their greater specific external surface area per unit mass and
      higher mesopore volume, as the pore blockage effect from large relative molecular
      mass NOM was alleviated. For micro-polluted water sample, the decrease of PAC
      particle size significantly enhanced the adsorption of organic matter fractions
      with relative molecular mass > 2 000, but had no notable improvement for that
      with relative molecular mass < 800.

PMID- 24455941
TI  - [Removal of nitrate from aqueous solution using cetylpyridinium chloride (CPC)
      modified activated carbon as the adsorbent].
AB  - Surfactant-modified activated carbon (SMAC) was prepared by loading
      cetylpyridinium chloride (CPC) onto activated carbon and used as adsorbents to
      remove nitrate from aqueous solution. The SMAC was effective for removing nitrate
      from aqueous solution. The SMAC exhibited much higher nitrate adsorption capacity
      than that of the unmodified activated carbon. The nitrate adsorption capacity for
      SMAC increased with increasing the CPC loading. The adsorption kinetics of
      nitrate on SMAC followed a pseudo-second-order kinetic model. The equilibrium
      adsorption data of nitrate on SMAC could be described by the Langmuir isotherm
      model. Based on the Langmuir isotherm model, the maximum nitrate adsorption
      capacity for SMAC with CPC loading amount of444 mmol per 1 kg activated carbon
      was determined to be 16.1 mg x g(-1). The nitrate adsorption capacity for SMAC
      decreased with the increasing solution pH. The presence of competing anions such
      as chloride, sulfate and bicarbonate reduced the nitrate adsorption capacity. The
      nitrate adsorption capacity for SMAC slightly decreased with the increasing
      reaction temperature. Almost 95% of nitrate molecules adsorbed on SMAC could be
      desorbed in 1 mol x L(-1) NaCl solution. The main mechanisms for the adsorption
      of nitrate on SMAC are anionic exchange and electrostatic attraction. The results
      of this work indicate that SMAC is a promising adsorbent for removing nitrate
      from aqueous solution.

PMID- 24455942
TI  - [Adsorption properties of modified graphene for methylene blue removal from
      wastewater].
AB  - In this study, cetyltrimethylammonium bromide (CTAB) was chosen to modify
      graphene, which was applied to remove methylene blue (MB) from aqueous solutions.
      The characteristics of graphene and modified graphene were characterized by X-ray
      diffraction (XRD), Fourier transform infrared spectrum (FTIR), thermal
      gravimetric analyzer (TGA), transmission electron microscopy (TEM), and scanning
      electron microscopy (SEM). The effects of factors including pH, contact time,
      temperature, and dosage on the adsorption properties of MB onto graphene and
      modified graphene were investigated. The results revealed that the addition of
      CTAB in preparation could obviously increase the specific surface area and
      improve the efficiency of removal. The adsorption processes were rapid within the
      first 15 min and reached equilibrium in about 120 min. The adsorption kinetics
      fitted well with the pseudo-second-order model. The optimal reaction temperature
      was 293 K, the optimal concentration of adsorbent dosage was 2 g x L(-1), and the
      initial pH value of the solution had little impact on the amount of adsorption.
      The adsorption capacity of MB on modified graphene inferred from the Langmuir
      model was 86.43 mg x g(-1) at 293 K, and the adsorption was an exothermic
      process.

PMID- 24455943
TI  - [Application of classical isothermal adsorption models in heavy metal ions/
      diatomite system and related problems].
AB  - In order to fully understand adsorption nature of Cu2+, Zn2+, Pb2+, Cd2+, Mn2+,
      Fe3+ onto natural diatomite, and to find problems of classical isothermal
      adsorption models' application in liquid/solid system, a series of isothermal
      adsorption tests were conducted. As results indicate, the most suitable isotherm
      models for describing adsorption of Pb2+, Cd2+, Cu2+, Zn2+, Mn2+, Fe3+ onto
      natural diatomite are Tenkin, Tenkin, Langmuir, Tenkin, Freundlich and
      Freundlich, respectively, the adsorption of each ion onto natural diatomite is
      mainly a physical process, and the adsorption reaction is favorable. It also can
      be found that, when using classical isothermal adsorption models to fit the
      experimental data in liquid/solid system, the equilibrium adsorption amount q(e)
      is not a single function of ion equilibrium concentration c(e), while is a
      function of two variables, namely c(e) and the adsorbent concentration W0, q(e)
      only depends on c(e)/W(0). Results also show that the classical isothermal
      adsorption models have a significant adsorbent effect, and their parameter values
      are unstable, the simulation values of parameter differ greatly from the measured
      values, which is unhelpful for practical use. The tests prove that four
      adsorption-components model can be used for describing adsorption behavior of
      single ion in nature diatomite-liquid system, its parameters k and q(m) have
      constant values, which is favorable for practical quantitative calculation in a
      given system.

PMID- 24455944
TI  - [Effects of nitrate on anoxic/anaerobic oxidation of methane in the aged refuse].
AB  - This work investigated the effects of nitrate on anoxic/anaerobic methane
      oxidation in the aged refuse landfilled 10-12 years by full-factor experiments.
      The results showed that under anoxic/anaerobic condition, nitrate could promote
      the removal of methane in the aged refuse. The contents of CH4 and NO3(-) -N had
      significant influences on the removal of CH4 and the generation of N2, and there
      were significant interactions as well (P < 0.05). The increasing initial CH4
      content evidently enhanced the removal of CH4 and the production of N2.
      Furthermore, the addition of NO3(-) -N obviously improved the de-nitrification
      process. The results suggested that nitrate reduction could be coupled to
      anoxic/anaerobic oxidation of methane in the aged refuse. In the experimental
      condition, the effort of coupling was most effective when the concentrations of
      CH4 and nitrate were 30% and 110 mg x kg(-1), respectively.

PMID- 24455945
TI  - [Study on the biotransformation of sulfate and ammonia in anaerobic conditions].
AB  - The anaerobic biological transformation characteristics of sulfate and ammonia
      were investigated in the upflow anaerobic biofilm reactor under inorganic
      nutrition condition by controlling different hydraulic retention time, NH4(+)-N
      and SO4(2-)-S ratio and HCO3- concentration in the influent. The results showed
      that NH4+ and SO4(2-) were synchronously removed. The maximum NH4(+) -N and SO4(2
      ) -S removal rate was 47.6 mg x (L x d)(-1) and 16.9 mg x (L x d)(-1),
      respectively, and the highest stable removal efficiency was more than 80% and
      43%. Obviously NO3(-) -N generated in the reaction and the maximum NO3(-) -N
      concentration was 77.6 mg x L(-1) in the effluent. Throughout the process S2- was
      not detected, but there was elemental sulfur generated attached to the surface of
      the biological sludge. During the whole process, different control conditions led
      to different n(NH4(+) -N) and n(SO4(2-) -S) conversion ratios, which showed that
      anaerobic biological NH4(+) and SO4(2-) transformation was not a simple serial
      reaction, more complex reactions and conversion pathways occurred in the reactor.

PMID- 24455946
TI  - [Characteristics of sulfate reduction-ammonia oxidation reaction].
AB  - The sulfate reduction-ammonia oxidation reaction with ANAMMOX sludge at
      autotrophic condition was implemented. It was found that the pH level decreased
      during the reaction. Elemental sulfur and nitrogen gas were the final products,
      while NO3(-) -N was the intermediate product during the sulfate reduction-ammonia
      oxidation reaction. The conversion ratio of NH4(+) -N/SO4(2-) -S decreased with
      the decrease in n(N)/n(S) (molar ratio) of raw water. n(N)/n(S) of raw water had
      little effect on the ammonia conversion ratio. Lower n(N)/n(S) could improve the
      SO4(2-)-S conversion ratio, but with more NH4(+) -N oxidized into NO3(-) -N,
      resulting in decreased n(TN)/n(TS) removal ratio. This indicates that the sulfate
      reduction-ammonia oxidation reaction is not an elementary reaction. Ammonia can
      be oxidized into NO2(-) -N or NO3(-) -N by sulfate. Shortening the reaction time
      would be conducive to nitrogen losses, because the reaction of NO3(-) -N
      production is the rate-limiting step.

PMID- 24455947
TI  - [Analysis of hydrogen-production performance in a UASB system at low pH].
AB  - This experiment used upflow anaerobic sludge blanket (UASB) with brown sugar
      water as fermentation substrate and sewage sludge as the initiation sludge of the
      reaction, which was made into granular sludge by adding activated carbon.
      Emphasis was placed on assessing the hydrogen production performance of the UASB
      hydrogen bio-production system in the stable ethanol-type fermentation. Under the
      conditions that the influent COD was 4000 mg x L(-1), the temperature was (35 +/-
      1) degrees C and the hydraulic retention time (HRT) was 8 h, a certain amount of
      NaHCO3 was added to adjust pH from 3.72 to 3.80, 3.85, 3.94 and 4.04, the
      hydrogen production rate increased correspondingly from the initial 5.5 L x d(-1)
      to about 7.0, 8.0, 9.5 and 6.0 L x d(-1), which was improved by 27.27%, 45.45%,
      72.73% and 9.09%, respectively. The highest hydrogen production rate and gas
      yield were observed at pH 3.94. The maximal gas yield was 15.83 L x d(-1), which
      was 1.75 times as high as the initial production. Meanwhile, the hydrogen
      production efficiency was 58.05%. This study broke through the lower limit pH
      value 4.0 in fermentative hydrogen production.

PMID- 24455948
TI  - [Preparation of red mud loaded Co catalysts: optimization using response surface
      methodology (RSM) and activity evaluation].
AB  - The removal efficiency of catalytic ozonation of bezafibrate (BZF) by red mud
      loaded Co catalysts (Co/RM) was used as the index value in statistical
      experimental designs. The most important factors influencing BZF degradation (P <
      0.05) in water were dipping mass of cobalt and calcination temperature. Under the
      conditions of 4.14% of dipping mass of cobalt and 389 degrees C of calcination
      temperature, the BZF removal efficiency was 71.29% as calculated by predictive
      value and a maximum removal efficiency of 70.74% was actually achieved. The
      experiment data was very close to the predictive value and the deviation was 1%
      (< 5%). The results indicated that the response surface methodology and
      mathematical model was reliable for experimental design. By comparing the
      differences of BZF degradation in RM and Co/RM processes, it was observed that
      Co/RM exhibited the greater catalytic activity. Furthermore, the surface
      structure and composition properties of the two catalysts were evaluated by N2
      adsorption, XRD and UV-Vis analysis. It was found that the specific surface area
      and total pore volume had the same variation trend, RM < Co/RM, which was
      consistent with the trend of catalytic ozonation. It was also found that Co3O4,
      the active component formed on the surface of RM by the addition of cobalt into
      red mud, enhanced the catalytic activity. Moreover, the dissolved metal
      concentration in the solution for catalytic ozonation of BZF degradation by RM or
      Co/RM was determined by ICP-OES. The results showed that for both catalysts there
      was no leaching of catalytic active components into the solution, which could
      suggest that the two catalysts were safe and could have certain application
      prospect.

PMID- 24455949
TI  - [Toxic effects of high concentrations of ammonia on Euglena gracilis].
AB  - Ammonia is among the common contaminants in aquatic environments. The present
      study aimed at evaluation of the toxicity of ammonia at high concentration by
      detecting its effects on the growth, pigment contents, antioxidant enzyme
      activities, and DNA damage (comet assay) of a unicellular microalga, Euglena
      gracilis. Ammonia restrained the growth of E. gracilis, while at higher
      concentrations, ammonia showed notable inhibition effect, the growth at 2 000 mg
      x L(-1) was restrained to 55.7% compared with that of the control; The contents
      of photosynthetic pigments and protein went up with increasing ammonia dosage and
      decreased when the ammonia concentration was above 1000 mg x L(-1); In addition,
      there was an obvious increase in SOD and POD activities, at higher concentration
      (2 000 mg x L(-1)), activities of SOD and POD increased by 30.7% and 49.4%
      compared with those of the control, indicating that ammonia could promote
      activities of antioxidant enzymes in E. gracilis; The degree of DNA damage
      observed in the comet assay increased with increasing ammonia concentration,
      which suggested that high dose of ammonia may have potential mutagenicity on E.
      gracilis.

PMID- 24455950
TI  - [Influence of image process on fractal morphology characterization of NAPLs
      vertical fingering flow].
AB  - Dyes are frequently used to visualize fingering flow pathways, where the image
      process has an important role in the result analysis. The theory of fractal
      geometry is applied to give quantitative description of the stain patterns via
      image analysis, which is helpful for finger characterization and prediction. This
      description typically involves two parameters, a mass fractal dimension (D(m))
      relative to the area, and a surface fractal dimension (D(s)) relative to the
      perimeter. This work detailed analyzes the influence of various choices during
      the thresholding step that transformed the origin color images to binary ones
      which are needed in the fractal analysis. One hundred and thirty images were
      obtained from laboratory two-dimension sand box infiltration experiments of four
      dyed non-aqueous phase liquids. Detailed comparisons of D(m) and D(s) were made
      respectively, considering a set of threshold algorithms and the filling of lakes.
      Results indicate that adjustments of the saturation threshold influence are less
      on both D(m) and D(s) in the laboratory experiments. The brightness threshold
      adjustments decrease the D(m) by 0.02 and increase the D(s) by 0.05. Filling
      lakes influence the D(m) less while the D(s) decrease by 0.10. Therefore the D(m)
      was recommended for further analysis to avoid subjective choices' influence in
      the image process.

PMID- 24455951
TI  - [Changing characteristics of organic matter and pH of cultivated soils in
      Zhejiang province over the last 50 years].
AB  - By comparing the current quality investigation data of cultivated soils in
      Zhejiang province with the past data, changing characteristics of organic matter
      and pH value of the soils in this province over last 50 years were analyzed. The
      results showed that content of organic matter and pH value of the cultivated
      soils changed greatly during past 50 years, and the changes varied with
      historical periods and soil types. From 1958 to 1980s, accumulation of soil
      organic matter was obvious, soil organic matter increased averagely by 40.34%,
      and the mean pH increased slightly by 0.05 of pH unit. From 1980s to 2008, the
      mean content of organic matter in paddy soils decreased by 5.58%. The changes of
      soil organic matter varied with distribution zones of the paddy soils. The mean
      content of organic matter of paddy soils in valley plain increased with time, and
      those in plain with water network, hilly area and coastal plain decreased with
      time. The mean contents of organic matter in fluvio-aquic soil and coastal saline
      soil in the year 2008 were 29.48% and 14.60% respectively higher than those in
      1980s. As compared with those obtained at 1980s, the cultivated soil in this
      province have been significantly acidified in the past thirty years, the mean pH
      value declined by 0.25 of pH unit, and the decline of pH value of paddy soils was
      greater than those of fluvio-aquic soil and saline soil. Changes in fertilization
      structure and conversion of paddy fields to upland were thought as main causes of
      the changes in both soil organic matter and pH value.

PMID- 24455952
TI  - [Study on selenium contents of typical selenium-rich soil in the middle area of
      Zhejiang and its influencing factors].
AB  - Based on the study of typical selenium-rich soil in the middle area of Zhejiang
      province, the influencing factors of selenium contents were summarized. We found
      that the selenium contents were controlled by the geological background. It was
      much higher in Tangxi, Zhijiang, and Jinhua than in other geological background
      regions. In addition, the contents of selenium in soil under different land use
      types showed a great difference. The content in the dry land was much more
      enriched than that in the paddy field. Further research showed that selenium was
      closely related to soil organic matter because of its adsorption and fixation.
      Moreover, we found that the soil texture was another important influencing
      factor. Selenium contents increased with increasing content of clay in the soil.

PMID- 24455953
TI  - [Spatial distribution characteristics of Fe and Mn contents in the new-born
      coastal marshes in the Yellow River estuary].
AB  - The spatial distribution characteristics of Fe and Mn contents in soils of nine
      different vegetation communities, located in the new-born marshes of the northern
      Yellow River estuary, were studied in May 2009. The results showed that the
      horizontal distributions of Fe and Mn contents showed an increasing tendency from
      Sparganiaceae-Potentilla supina marsh to bare flat. The vertical distribution
      characteristics of Fe and Mn contents in different marsh soils fluctuated
      significantly with the vegetation succession. The soil parent materials
      determined the Fe, Mn contents in the new-born marshes, and seawater, vegetations
      and soil fine particle also had important influences on their contents. Further
      analysis showed that Fe contents had significant positive correlation with Mn
      contents (P < 0.01). Fe, Mn contents also showed significant correlations with
      silt, clay, TN, NO3(-) -N and organic matter (P < 0.05), indicating that Fe and
      Mn had close relationships with nitrogen, and the contents of soil fine particles
      and organic matter were the dominant factors affecting the distribution of Fe and
      Mn in soils. In addition, the Fe contents ranged from 16.49 g x kg(-1) to 33.11 g
      x kg(-1) and the average was 22.54 g x kg(-1), which was close to the Fe contents
      in the tidal marshes of north Jiangsu, the Loess Plateau and the China soil
      background value, but slightly lower than those in the marshes of the Yangtse
      River estuary, the mangrove swamps and inland lake wetland. The Mn contents
      ranged from 305.87 mg x kg(-1) to 711.39 mg x kg(-1) and the average was 451.09
      mg x kg(-1), which was lower than the Mn contents in the Loess Plateau and the
      China soil background value. Hydrology and Water Resources Survey Bureau of the
      Yellow River Estuary, Dongying 257091, China)

PMID- 24455954
TI  - [Level, composition and sources of medium-chain chlorinated paraffins in soils
      from Chongming Island].
AB  - In order to understand the contents, spatial distribution and sources of medium
      chain chlorinated paraffins (MCCPs) in the soils from Chongming Island, the
      concentrations of MCCPs in 27 soil samples were analyzed by GC-ECNI-MS. The total
      concentrations of MCCP8 (sigma MCCPs) in all samples ranged from 2.56-96.3 ng x
      g(-1), with a median of 7.32 ng x g(-1). All soil samples were classified into
      two categories by cluster analysis. C14-MCCPs and C15-MCCPs, and Cl5-MCCPs and
      Cl6-MCCPs were the most predominant carbon and chlorine congener groups in most
      of the samples, accounting for 29.8% and 28.9%, and 29.9% and 23.3%,
      respectively. C14-MCCPs were the most predominant carbon congener groups in some
      samples, accounting for 68.5%, which was similar to that of CP-52. Atmospheric
      deposition and soil-air exchange were the major sources of MCCPs for soils in
      Chongming. Soils at a few sites were probably contaminated by sewage sludge from
      sewage treatment plants (STPs) or other unidentified source. No significant
      correlations were observed between MCCPs and TOC. The correlation analysis also
      showed significant correlation among the carbon congener groups of MCCPs, which
      suggested that MCCP congener groups might have been derived from similar sources.
      Compared to other studies at home and abraod, the MCCPs concentrations in the
      present study were at a lower level.

PMID- 24455955
TI  - [Distribution characteristics of organochlorine pesticides in soil from Daiyun
      Mountain Range in Fujian, China].
AB  - Totally 101 typical surface soil samples were collected from Daiyun Mountain
      Range, and 20 compounds of OCPs were analyzed by a Ni electron capture detector
      (GC-ECD) to investigate the horizontal distribution and composition of
      organochlorine pesticides (OCPs) in the surface soil of Daiyun Mountain Range.
      The results showed that all OCPs were detected in the soil samples. The detection
      ratios of OCPs were all over 90%, except for Endrin and beta-HCH. The sum
      concentration of HCHs, DDTs, Endosulfan and Endosulfan sulfate, accounted for
      79.51% of the total OCPs, which were considered to be the dominant OCPs in the
      Daiyun Mountain Range. The OCPs concentrations in the surface soils ranged from
      2.56 to 465.99 ng x g(-1) with a mean value of 38.00 ng x g)(-1). Compared with
      other regions, the concentrations of HCHs and DDTs in this study stayed in a low
      pollution level. Endosulfan and Endosulfan sulfate showed a certain degree of
      risk in the surface soil of the study area. Source analysis showed that new input
      of lindane and dicofol might occur in the survey region. The historical
      application was the prime source of Endosulfan. The residue level of OCPs in
      different lands was in the following order: paddy land > vegetable land >
      orchard. The OCPs pollution of orchard soil was primarily due to the new input of
      lindane and dicofol, while the pollution of paddy land was mainly from the usage
      of Endosulfan.

PMID- 24455956
TI  - [Levels of PCDD/Fs and dioxin-like PCBs in soils near E-waste dismantling sites].
AB  - One hundred and fifty one soil samples from 125 sampling points were collected
      near E-waste dismantling sites and analyzed for polychlorinated dibenzo-p-dioxins
      and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs).
      Total concentration of PCDD/Fs in topsoil samples ranged from 280 pg x g(-1) to 7
      010 pg x g(-1) dry weight with the mean value of 1 380 pg x g(-1) dry weight. The
      mean value of the second layer and the deepest layer is 63% and 38% of that of
      top soils, respectively. The toxic equivalent quantity (TEQ) of PCDD/Fs in top
      soils ranged from 1.4 pg x g(-1) to 94.8 pg x g(-1) (I-TEQ). According to the
      guidelines for TEQ concentrations established in Germany, 19 of 125 topsoil
      samples (15% of the total topsoil samples analyzed) could not be expected to pose
      human health hazards. The rest of 85% of top soils needs investigations of source
      identification. If the contribution of PCB to TEQ was considered, 98% of top
      soils need investigations of source identification. Principle component analysis
      (PCA) is used to identify the PCDD/Fs sources. The homologue profiles of PCDD/Fs
      showed that dismantling activities are the main emission resources of the PCDD/Fs
      from thermal processes, also are the main emission resources of the PCDD/Fs in
      soils of this area.

PMID- 24455957
TI  - [Chemical form changes of exogenous water solution fluoride and bioavailability
      in tea garden soil].
AB  - Pot experiments and the sequential extraction method were conducted to study the
      chemical form changes of exogenous water solution fluoride in tea garden soil and
      their contribution to fluoride accumulation of tea plant. The results showed that
      the background concentration of all chemical forms of fluoride had little changes
      with time treatment, which was in a relatively stable state. The exogenous water
      solution fluoride adding to the soils was rapidly transformed to other fractions.
      Under the 10 mg x kg(-1) fluoride treatment, the concentration of water solution
      fluoride increased firstly and then decreased with time treatment, the
      concentration of organic matter fluoride and Fe/Mn oxides fluoride decreased, the
      concentration of exchangeable fluoride was not different before and after the
      treatment (P > 0.05), and the concentration of residual fluoride was in a
      relatively stable state; under the 200 mg x kg(-1) fluoride treatment, the
      concentration of water solution fluoride, Fe/Mn oxides fluoride and organic
      matter fluoride decreased with time treatment, the concentration of exchangeable
      fluoride increased firstly and then decreased, showed no difference before and
      after the treatment (P > 0.05), and the concentration of residual fluoride
      increased, with some differences compared with 10 mg x kg(-1) fluoride treatment.
      The concentration of total fluoride in root, stem and leaf had significant
      differences under 0-10 mg x kg(-1) fluoride treatment (P < 0.05), while showed no
      difference from 10 to 100 mg x kg(-1) fluoride treatment (P > 0.05). Step
      regression analysis suggested the contribution of all chemical forms of fluoride
      to the concentration of water solution fluoride and total fluoride of root, stem
      and leaf had some differences, there was a remarkable regression relationship
      among the content of total fluoride in leaf and water solution fluoride, organic
      matter fluoride, Fe/Mn oxides fluoride and residual fluoride in soil, however, no
      significant difference for water solution fluoride of leaf was found.

PMID- 24455958
TI  - [Effects of arbuscular mycorrhizal fungi on the vegetation restoration of
      different types of coal mine spoil banks].
AB  - A greenhouse pot experiment was conducted to investigate the influence of
      arbuscular mycorrhizal (AM) fungi Glomus etunicatum (GE) and Glomus versiforme
      (GV) on the plant growth, nutrient uptake, C: N: P stoichiometric, uptake of
      heavy metals by maize (Zea mays L.) grown in three types of coal mine spoil
      banks. The aim was to provide a technical basis for the revegetation of coal mine
      spoil banks in grassland ecosystem. The results indicated that the symbiotic
      associations were successfully established between two isolates and maize grown
      in the three substrates, with an average mycorrhizal colonization rate ranging
      from 36% to 54%. The colonization of two AM fungi significantly increased the dry
      weight of maize grown in recent discharged and weathered coal mine spoils and GE
      increased those grown in weathered coal mine spoil. Inoculation with AM fungi
      promoted the uptake of N, P and K by maize to varying degrees. In addition,
      inoculation with GE and GV also decreased C: N: P ratios, supporting the growth
      rate hypothesis, and had significantly differences on concentrations of Cu, Fe,
      Mn and Zn in shoots and roots of maize. The results indicated that GE and GV had
      different mycorrhizal effects on maize in the three types of substrates. GV was
      more suitable for the revegetation of recent discharged coal mine spoil and
      weathered coal mine spoil, while GE was more suitable for the revegetation of
      spontaneous combusted coal mine spoil. The experiment demonstrates that AM fungi
      have a potential role for maize to enhance the ability to adapt the composite
      adversity of different types of coal mine spoil and play a positive role in the
      revegetation of different coal mine spoil banks. Further field experiments should
      be conducted to evaluate the practical effects of AM fungi on the vegetation
      restoration of different types of coal mine spoil under field conditions.

PMID- 24455959
TI  - [Effects of the arbuscular mycorrhizal fungi on environmental phytoremediation in
      coal mine areas].
AB  - To resolve the key environmental problems in coal mine areas of environmental
      phytoremediation, symbiosis of arbuscular mycorrhizal fungi (AMF) and Amorpha
      fruticosa was investigated. Effects of AMF on the root growth of Amorpha
      fruticosa and degenerated soil in coal mining subsidence area were studied.
      Results showed that after 5 months inoculation, AMF improved the shoot and root
      growth of Amorpha fruticosa. After inoculation with arbuscular mycorrhiza (AM)
      for 5 months, the inoculation significantly increased root colonization of
      Amorpha fruticosa. Total glomalin and easily extractable glomalin were increased
      significantly in the incubated soil. The content of phosphorus and organic matter
      were increased in the rhizosphere soil. Population of microorganism increased
      obviously. All the above results show that their ecological effects are
      significantly improved. AM would promote rhizosphere soil that will help the
      sustainability of ecological systems in mining area. It is really of great
      significance to keep the ecological system stability.

PMID- 24455960
TI  - [Preliminary analysis of manganese uptake mechanism in the hyperaccumulator
      Phytolacca americana L].
AB  - Phytolacca americana L. (P. americana) is a manganese (Mn) hyperaccumulator plant
      discovered in southern China, and knowledge of Mn uptake characteristics and
      mechanisms on this plant may provide essential and critical information for
      phytoremediation. Synchrotron radiation X-ray fluorescence spectroscopy (SRXRF)
      microprobe was empolyed in this study to explore the Mn distribution in the root
      cross-section of P. americana, and effects of metabolic inhibitors (DNP and
      Na3VO4) and Ca-channel inhibitor (LaCl3) on Mn uptake of P. americana was also
      investigated under laboratory conditions. Results showed that P. americana has
      strong abilities for absorpting and accumulating Mn, and the Mn concentration in
      root, stem, and leaf of P. americana may reach up to 402, 208, and 601 mg x kg(
      1) DW, respectively, even only treated with 5 micromol x L(-1) Mn. The highest Mn
      content can be found in the vascular bundle of root, and then the epidermis,
      while the lowest Mn content can be observed in the cortex. The Mn content
      increased when shifted from cortex to vascular bundle, indicating that there was
      an active transportation in Mn absorption of P. americana root, and the
      inhibitory effect of DNP and Na3VO4 on Mn uptake further verified the
      possibilities of active absorption. The Mn uptake was inhibited by 30% with
      LaCl3, suggesting that Mn uptake in P. americana also closely related to the Ca
      channel.

PMID- 24455961
TI  - [Research on the bioaccesibility of HgS by Shewanella oneidensis MR-1].
AB  - The biological dissolution and methylation of solid HgS by Shewanella oneidensis
      MR-1 and influenced factors under laboratory conditions were studied. Results
      showed that S. oneidensis MR-1 could grow well at the low concentration of Na2S,
      but its growth was inhibited at the high concentration of Na2S, which mainly
      happened in the prolonged lag phase. Iron reducing bacteria S. oneidensis MR-1
      could access the solid mercuric sulfide, and rapidly promote the biological
      dissolution and methylation of HgS. In the appropriate range of sulfide to S.
      oneidensis MR-1, the biological solubility of HgS was enhanced with the
      increasing concentration of Na2S, but the methylation just promoted at the low
      Na2S concentration, and it would be inhibited when the concentration is high. In
      addition, weakly acidic environment was more beneficial to biological dissolution
      and methylation of HgS than acidic, neutral or alkaline conditions by S.
      oneidensis MR-1.

PMID- 24455962
TI  - [Study on IEUBK model localization based on behavior parameters of children from
      southwestern China].
AB  - IEUBK (Integrated Exposure Uptake Biokinetic Model for Lead in Children) model
      was developed and recommended by the US Environmental Protection Agency. In order
      to apply IEUBK model to China, we firstly performed sensitivity analysis, which
      showed that simulated blood Pb (PbB) concentration was most sensitive to
      soil/dust exposure pathway. In-home surveys were conducted in Y province of China
      to gather information on children's behavior parameters and environmental samples
      for parameters localization. Finally the verified model was applied to predict
      children's PbB level in comparison with that modeled by default parameter values.
      Results showed that geometric mean values of children's PbB concentration were
      5.28 microg x dL(-1), 5.77 microg x dL(-1), 6.03 microg x dL(-1) and 6.32 microg
      x dL(-1) before and 5, 10 and 20 years after the establishment of a new factory
      in the neighboring G province. The simulated PbB after 20 years was 61.39% lower
      by original model than that by the localized model.

PMID- 24455963
TI  - [Sorption and desorption characteristics of different structures of organic
      phosphorus onto aluminum (oxyhydr) oxides].
AB  - The sorption and desorption characteristics of four kinds of organic phosphorus
      with different molecular structures (glycerophosphate (GP), glucose-6-phosphate
      (G6P), adenosine triphosphate (ATP), and myo-inositol hexakisphosphate (IHP)) on
      three kinds of aluminum (oxyhydr)oxides (amorphous Al(OH)3, boehmite, and alpha
      Al2O3) were studied. The underlying mechanisms were also illustrated. Results
      showed that the maximum sorption amounts of OP onto Al (oxyhydr)oxides, on a per
      gram dry weight basis, decreased as following: amorphous Al(OH)3 > boehmite >
      alpha-Al2O3. This mainly related to the mineral crystallinity and surface
      heterogeneity. With the exception of sorption of IHP on amorphous Al (OH)3, the
      maximum sorption density decreased with increasing molecular weight (MW) of OP,
      following the order: GP > G6P > ATP > IHP. However, the sorption amount of IHP on
      amorphous Al (OH)3 was much higher than those of other OP, due to the
      transformation of surface complexes of IHP to surface precipitation and thus
      enhancing the sorption. The sorption kinetics results showed that sorption of OP
      underwent the first onset rapid sorption, i. e. a certain amount of sorption
      occurred within an onset extremely short period, and a following long and slow
      sorption process. Amorphous Al (OH)3 had the greatest onset rapid sorption
      density, and the onset rapid sorption density of OP on Al (oxyhydr) oxides
      decreased with increasing MW. Desorption capacities of OP by KCl and citrate
      solutions related to the surface affinity between OP and boehmite. Initial
      desorption percentages by KCl decreased in the order: G6P (10.53%) > GP(6.91%) >
      ATP (3.06%) > IHP (0.8%). The maximum desorption percentages of OP by citrate
      were 4-5 times greater than those by KCl. During resorption process of P by KCl,
      the maximum desorption rate achieved after a fast desorption in a few hours,
      followed by diffusion-resorption during which the desorption percentage gradually
      decreased. Specially, both diffusion-resorption and surface precipitation
      promoted the resorption of IHP on mineral surface. Conclusively, the strong
      specific sorption of OP occurs on the surface of Al (oxyhydr) oxides, and
      molecular structure and size of OP as well as the crystallinity and crystal
      structure of minerals are the key factors affecting the interfacial reactions and
      environmental behaviors of OP.

PMID- 24455964
TI  - [Study on the occurrence of ferrum in coal by ultrasound-assisted sequential
      chemical extraction].
AB  - To reveal the occurrence of Ferrum in coal, seven coal samples were selected
      according to the different contents of ferric oxide in the coal ash, and the
      content of Ferric element was determined by atomic absorption spectrophotometer
      (AAS) using nitric acid-perchloric acid-hydrofluoric acid wet digestion. Modes of
      occurrence of ferrium in the seven coal samples were studied by AAS using
      ultrasound-assisted sequential chemical extraction experiment (SCEE). Ultrasound
      promoted the contact of the extraction reagent with the coal particles and
      enhanced the dissolution process by producing characteristic acoustic
      cavitations, which greatly shortened the experimental time. The total amount of
      ferrium obtained by sequential extraction was approximate to the result of wet
      digestion, which indicated the procedure of SCEE was reasonable. The results
      showed that the ferric element mainly occurred in forms of carbonate state, Fe-Mn
      oxides state, sulfide state, sialic state and organic bound Fe in these coal
      samples. Among the various forms of these occurrences, the content of carbonate
      was the least, below 3.1%, while the content of sulfide was the dominant
      occurrence, ranging from 40% to 81.5%.

PMID- 24455965
TI  - [A review of uptake, translocation and phytotoxicity of engineered nanoparticles
      in plants].
AB  - With the increasing use of engineered nanoparticles, these materials will
      inevitably be released into the environment with unknown consequences. The
      interactions between engineered nanoparticles and plants are of particular
      concern, and the uptake by plants may constitute one of the main routes of
      exposure for species at a higher trophic level, leading to possible
      biomagnification of nanoparticles in the food chain. A review of the current
      literature shows that nanoparticles can be taken up by plants and cause
      phytotoxicity. The mechanisms by which engineered nanoparticles penetrate plant
      cells are still not well understood. Most of the studies have been performed with
      a few plant species under non-natural conditions such as hydroponics, and have
      included only the germination or seedling growth stage. Nanoparticles may undergo
      biotransformation and subsequent translocation within plants, although the
      mechanisms are poorly understood. Phytotoxicity is an important aspect for
      assessing potential environmental impacts of nanoparticles, but the mode of
      toxicity remains to be investigated.

PMID- 24455966
TI  - Self-assembled all-conjugated block copolymer as an effective hole conductor for
      solid-state dye-sensitized solar cells.
AB  - An all-conjugated diblock copolymer, poly(2,5-dihexyloxy-p-phenylene)-b-poly(3
      hexylthiophene) (PPP-b-P3HT), was synthesized and applied as a hole transport
      material (HTM) for the fabrication of solid-state dye-sensitized solar cells (ss
      DSCs). This copolymer is characterized by an enhanced crystallinity, enabling its
      P3HT component to self-organize into interpenetrated and long-range-ordered
      crystalline fibrils upon spin-drying and ultimately endowing itself to have a
      faster hole mobility than that of the parent P3HT homopolymer. Transient
      photovoltage measurements indicate that the photovoltaic cell based on PPP-b-P3HT
      as the HTM has a longer electron lifetime than that of the reference device based
      on P3HT homopolymer. Moreover, comparing the two ss-DSCs in terms of the
      electrochemical impedance spectra reveals that the electron density in the TiO2
      conduction band is substantially higher in the PPP-b-P3HT device than in the P3HT
      cell. Above observations suggest that the PPP block facilitates an intimate
      contact between the copolymer and dye molecules absorbed on the nanoporous TiO2
      layer, which significantly enhances the performance of the resulting device.
      Consequently, the PPP-b-P3HT ss-DSC exhibits a promising power conversion
      efficiency of 4.65%. This study demonstrates that conjugated block copolymers can
      function as superior HTMs of highly efficient ss-DSCs. 

PMID- 24455967
TI  - Gain of chromosome 1q21 is an independent adverse prognostic factor in light
      chain amyloidosis patients treated with melphalan/dexamethasone.
AB  - Chromosomal aberrations of plasma cells are well established pathogenetic and
      prognostic factors in multiple myeloma, but their prognostic implication in
      systemic light chain (AL) amyloidosis is unclear. Therefore, the aim of this
      study was to identify prognostic cytogenetic risk factors by interphase FISH in a
      series of 103 consecutive AL amyloidosis patients treated uniformly with
      melphalan/dexamethasone as first-line therapy. Detection of gain of 1q21 was
      predictive for a poor overall survival (OS) (median 12.5 versus 38.2 months, p =
      0.002). Hematologic event free survival (hem EFS) for gain of 1q21 was 5.0 versus
      8.5 months in median (p = 0.08) and haematologic remission rates (>=VGPR) after
      three cycles were 5% versus 25% (p = 0.06). Most important, in multivariate
      concordance analyses the adverse prognosis carried by gain of 1q21 was retained
      as an independent prognostic factor (OS: p = 0.003, average hazard ratio (AHR) =
      3.64, hemEFS: p = 0.008, AHR = 2.35), along with the well established Mayo
      cardiac staging. Patients with t(11;14) had a longer median OS with 38.2 months
      versus 17.5 months, though no statistical significance was reached. Deletion
      13q14 and hyperdiploidy turned out to be prognostically neutral. In conclusion,
      we have identified gain of 1q21 as an independent adverse prognostic factor in AL
      amyloidosis patients treated with standard chemotherapy.

PMID- 24455968
TI  - Humic substances enhance chlorothalonil phototransformation via photoreduction
      and energy transfer.
AB  - The photodegradation of chlorothalonil, a polychlorinated aromatic fungicide
      widely used in agriculture, was investigated under ultraviolet-visible
      irradiation in the presence and absence of different humic substances that
      significantly enhance the chlorothalonil phototransformation. On the basis of a
      kinetic model, an analytical study, the effect of scavengers, the chlorothalonil
      phosphorescence measurement, and varying irradiation conditions, it was possible
      to demonstrate that this accelerating effect is due to their capacity to reduce
      the chlorothalonil triplet state via H-donor reaction and to energy transfer from
      the triplet humic to ground state chlorothalonil. Energy transfer occurs at
      wavelengths below 450 nm and accounts for up to 30% of the reaction in
      deoxygenated medium upon irradiation with polychromatic light (300-450 nm). This
      process is more important with Elliott humic and fulvic acids and with humic
      acids extracted from natural carbonaceous material than with Nordic NOM and
      Pahokee peat humic acids. The obtained results are of high relevance to
      understanding the processes involved in chlorothalonil phototransformation and
      the photoreactivity of humic substances. Chlorothalonil is one of the rare
      molecules shown to react by energy transfer from excited humic substances. 

PMID- 24455969
TI  - Solid solution alloy nanoparticles of immiscible Pd and Ru elements neighboring
      on Rh: changeover of the thermodynamic behavior for hydrogen storage and enhanced
      CO-oxidizing ability.
AB  - Pd(x)Ru(1-x) solid solution alloy nanoparticles were successfully synthesized
      over the whole composition range through a chemical reduction method, although Ru
      and Pd are immiscible at the atomic level in the bulk state. From the XRD
      measurement, it was found that the dominant structure of Pd(x)Ru(1-x) changes
      from fcc to hcp with increasing Ru content. The structures of Pd(x)Ru(1-x)
      nanoparticles in the Pd composition range of 30-70% consisted of both solid
      solution fcc and hcp structures, and both phases coexist in a single particle. In
      addition, the reaction of hydrogen with the Pd(x)Ru(1-x) nanoparticles changed
      from exothermic to endothermic as the Ru content increased. Furthermore, the
      prepared Pd(x)Ru(1-x) nanoparticles demonstrated enhanced CO-oxidizing catalytic
      activity; Pd0.5Ru0.5 nanoparticles exhibit the highest catalytic activity. This
      activity is much higher than that of the practically used CO-oxidizing catalyst
      Ru and that of the neighboring Rh, between Ru and Pd.

PMID- 24455970
TI  - Alkaline phosphatase is independently associated with renal function in
      normoalbuminuric type 1 diabetic patients.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with an increased
      prevalence of chronic kidney disease in patients with type 1 diabetes. The aim of
      this study was to explore the relationship between markers of NAFLD, namely
      concentrations of aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), alkaline phosphatase (ALK), gamma-glutamyltransferase (GGT), bilirubin,
      and renal function in type 1 diabetic patients. This study included 313
      normoalbuminuric type 1 diabetic patients with estimated glomerular filtration
      rate (eGFR) >60 mL/min/1.73 m(2), without clinical evidence of cirrhosis or other
      causes of chronic liver disease and before any interventions with statins,
      angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor
      blockers. ALT, GGT, and bilirubin levels were significantly higher in subjects in
      the highest quartile of serum creatinine compared to those in lowest quartile (21
      vs. 20 U/L, 18 vs. 14 U/L, and 14 vs. 10 umol/L, respectively, for all p < 0.05).
      ALK levels were significantly higher in subjects in the highest quartile of
      urinary albumin excretion rate compared to those in lowest quartile (71 vs. 69
      U/L, p = 0.03), as well as in hyperfiltrating subjects compared to those with
      normal or mildly impaired eGFR (81 vs. 68 and 64 U/L, p < 0.001). In a multiple
      logistic regression model adjusted for age, sex, duration of diabetes, HbA1c, and
      body mass index (BMI), only ALK levels were significantly associated with
      disturbances in serum creatinine and eGFR in our subjects (p <= 0.007), with odds
      ratios of 0.98-1.02. NAFLD associated markers, particularly ALK, are associated
      with renal function in normoalbuminuric type 1 diabetic patients.

PMID- 24455971
TI  - Relationship between human chorionic gonadotropin serum levels and the risk of
      ovarian hyperstimulation syndrome.
AB  - The object of this retrospective cohort study was to determine if hCG levels
      correlate with ovarian hyperstimulation syndrome (OHSS) risk after adjustment for
      other risk factors during in vitro fertilization (IVF). We measured serum hCG
      approximately 12 h after hCG trigger in women undergoing 406 cycles of controlled
      ovarian hyperstimulation for IVF between June 2006 and December 2009. Serum hCG
      levels were measured 12 h after trigger. Bivariate logistic regression was used
      to assess the association between patient and cycle characteristics and OHSS. In
      our series, mild to moderate OHSS occurred in 9% (38/406), and severe OHSS
      diagnosed in 1.5% (6/406) of IVF cycles. OHSS risk was increased in younger women
      (<30 years old: adjusted odds ratio: aOR 2.46, 95% confidence interval: CI 1.14
      5.34), increased number of oocytes (11-20: aOR 6.79, 95% CI 1.97-23.40; >20: aOR
      17.55, 95% CI 4.84-63.70), and increase E2 levels (>=3,000 pg/mL: aOR 2.59, 95%
      CI 1.33-5.05), but was unrelated to hCG level (100-200 IU/L: aOR 1.53, 95% CI
      0.60-3.91; >=200 IU/L: aOR 1.42 95% CI 0.48-4.20). These results indicate that
      OHSS risk during IVF is unrelated to serum hCG level measured approximately 12 h
      after trigger.

PMID- 24455972
TI  - Hyperstimulation syndrome: the levels of inhibin A and B in sera and follicular
      fluids.
AB  - Ovarial hyperstimulation syndrome (OHSS) represents a serious problem encountered
      during in vitro fertilization (IVF). We examined 10 patients with OHSS and 50
      women also hormonally stimulated in the process of IVF who had no complications.
      In all women, we evaluated the number of obtained oocytes and the level of
      inhibins A and B in sera and follicular fluid collected at the time of ovarial
      puncture, the day embryo transfer and on the day of positivity for hCG. The level
      of inhibin B in both fluids was significantly higher (t = 0.0403) in women with
      high quality of oocytes. The higher level of inhibin A was detected in patients
      with OHSS at the time of oocyte collection and on the day of embryo transfer.
      Inhibin B was elevated only at the time of oocyte collection. The levels of
      inhibin A and B were identical in follicular fluids collected from both ovaries.
      We observed no statistically significant differences between the levels of
      inhibin A and B in follicular fluids of women in the absence of OHSS. Evaluation
      of serum levels of inhibin A and B at the time of oocyte collection may
      contribute to the prognosis and prevention of OHSS.

PMID- 24455973
TI  - Tuberculosis screening and isoniazid preventive therapy implementation: a
      Brazilian experience.
AB  - Tuberculosis Preventive therapy has been used since the 1960s for both mass
      treatment of populations and for targeted therapy to high-risk groups such as
      children. The World Health Organization (WHO) recommends the use of Isoniazid
      preventive therapy (IPT) as one of the strategies to reduce the TB burden among
      people living with HIV infection. However, its uptake in countries with high TB
      burden has been poor. One of the main barriers to its widespread implementation
      is concerns around the ruling out of active TB. WHO, in its revised guidelines on
      IPT, recommends the use of a symptom-based algorithm for TB screening. The
      randomized clinical trial evaluated here explores the effect of an intervention,
      in the form of training the clinic staff to screen for TB, use of tuberculin skin
      test and IPT to treat latent TB infection, and assess its effect on rates of TB
      and death in HIV infected.

PMID- 24455974
TI  - 'Newcomer adaptation': a lens through which to understand how nursing students
      fit in with the real world of practice.
AB  - AIMS AND OBJECTIVES: To present a discussion on newcomer adaptation as a lens
      through which to understand how nursing students adapt to clinical practice and
      raise awareness of strategies that can be used to enhance their learning
      experiences. BACKGROUND: Socialisation is an important factor that facilitates
      students' learning in the clinical setting. Therefore, it is beneficial to
      examine organisational socialisation literature, particularly that pertaining to
      newcomer adaptation. DESIGN: This is a critical review of organisational
      socialisation literature. METHODS: Seminal literature and more recent research in
      the field of organisational socialisation and newcomer adaptation were accessed.
      In addition, nursing and allied health literature examining students'
      socialisation and the clinical learning environment was retrieved. CONCLUSIONS:
      It is revealed in this article that to create an appropriate clinical learning
      environment, an understanding of socialisation tactics could be beneficial. Role
      modelling is deemed crucial to successful newcomer adaptation. Peer support is
      necessary but must be advocated with caution as it can have a negative impact
      when students form a 'parallel community'. Students with some knowledge of the
      workplace tend to adapt more easily. Likewise, students' disposition and, in
      particular, their confidence can also enhance the socialisation process.
      RELEVANCE TO CLINICAL PRACTICE: Both the organisation and the student can impact
      on how successfully the nursing student 'fits in'. Understanding this through the
      lens of newcomer adaptation means that strategies can be put in place to
      facilitate this process.

PMID- 24455975
TI  - Comprehensive strategy for proton chemical shift prediction: linear prediction
      with nonlinear corrections.
AB  - A fast 3D/4D structure-sensitive procedure was developed and assessed for the
      chemical shift prediction of protons bonded to sp3carbons, which poses the maybe
      greatest challenge in the NMR spectral parameter prediction. The LPNC (Linear
      Prediction with Nonlinear Corrections) approach combines three well-established
      multivariate methods viz. the principal component regression (PCR), the random
      forest (RF) algorithm, and the k nearest neighbors (kNN) method. The role of RF
      is to find nonlinear corrections for the PCR predicted shifts, while kNN is used
      to take full advantage of similar chemical environments. Two basic molecular
      models were also compared and discussed: in the MC model the descriptors are
      computed from an ensemble of the conformers found by conformational search based
      on Metropolis Monte Carlo (MMC) simulation; in the 4D model the conformational
      space was further expanded to the fourth dimension (time) by adding molecular
      dynamics to the MC conformers. An illustrative case study about the application
      and interpretation of the 4D prediction for a conformationally flexible
      structure, scopolamine, is described in detail.

PMID- 24455976
TI  - Interleukin-20 receptor expression in the trabecular meshwork and its implication
      in glaucoma.
AB  - PURPOSE: To determine whether interleukin-20 receptors (IL-20R) are expressed in
      trabecular meshwork cells and the effect of a T104M mutation in IL-20R2 on
      downstream cellular functions. METHODS: Evaluation of signal transducer and
      activator of transcription (STAT)3 phosphorylation and generic matrix
      metalloproteinase (MMP) activity in primary open angle glaucoma (POAG) dermal
      fibroblasts (pHDF) with the T104M IL-20R2 mutation were compared with normal
      human dermal fibroblasts (HDF). Expression of IL-20R1 and IL-20R2 in human
      trabecular meshwork (HTM) cells was determined by immunohistochemistry and
      western immunoblotting. RESULTS: A T104M mutation in IL20-R2 was identified in a
      large POAG family in which the GLC1C locus was originally mapped. pHDFs harboring
      this mutation had significantly increased phosphorylated STAT3 (pSTAT3) activity
      compared with normal HDFs. However, stimulation with either IL-19 or IL-20 for 15
      min resulted in significantly decreased levels of pSTAT3 in pHDFs compared with
      controls. Generic MMP activity was significantly decreased in pHDFs compared with
      controls after stimulation with IL-20 for 24 h. Both IL-20R1 and IL-20R2
      receptors were expressed in HTM cells by western immunoblot and
      immunofluorescence, and they appeared to be up-regulated in response to cytokine
      treatment. CONCLUSIONS: A T104M mutation in IL-20R2 significantly impacts the
      function of this receptor as shown by decreased pSTAT3 levels and generic MMP
      activity. Reduced MMP activity may affect the ability of glaucoma patients to
      alter outflow resistance in response to elevated intraocular pressure.

PMID- 24455977
TI  - Failure of repeated treatment with praziquantel and arthemeter in four patients
      with acute schistosomiasis.
AB  - Schistosomiasis is on the rise but still difficult to treat in international
      travelers; it should be suspected in patients returning from endemic areas.
      Praziquantel (PZQ) is not effective and may aggravate symptoms. More recently,
      combination treatment with artemisinin derivatives have shown promising results.
      We report four cases of acute schistosomiasis (AS) in which several courses of
      combined therapy had been necessary to obtain negative serology. 

PMID- 24455978
TI  - Local and systemic tissue response submitted to injection of 2 and 30%
      polymethylmethacrylate in rats' tongue.
AB  - INTRODUCTION: Adverse effects on the oral mucosa after the use of dermal fillers
      have been reported due to their increased use for facial aesthetics. OBJECTIVE:
      This study aimed to evaluate, clinically and histologically, the local and
      systemic effects of two concentrations of polymethylmethacrylate (PMMA) dermal
      filler in rats. MATERIAL AND METHODS: Fifty-four female rats were allocated into
      three treatment groups (2% PMMA, 30% PMMA and 0.9% NaCl), according to the
      substance injected in the tongue, and three experimental periods: 7, 60 and 90
      days. The rats were clinically evaluated and then euthanised, and their tongue
      and right kidney removed. The histological sections were stained with
      haematoxylin/eosin and picrosirius. RESULTS: Clinically, significant differences
      were found between test groups as to the occurrence of nodules (Kruskal-Wallis; p
      < 0.001). Histologically, there was greater inflammatory response in the PMMA
      compared with control (Kruskal-Wallis; p < 0.001). 30% PMMA had greater collagen
      formation (anova mixed models; p < 0.01). No migration of the material towards
      kidney was found. CONCLUSION: Polymethylmethacrylate induced intense reaction in
      the initial period of observation (7 days), followed by gradual decrease during
      the study, favouring the presence of fibroplasia adjacent to the material.

PMID- 24455979
TI  - A Pilot Study Comparing Observational and Questionnaire Surrogate Measures of
      Pesticide Exposure Among Residents Impacted by the Ecuadorian Flower Industry.
AB  - Self-reported measures of residential pesticide exposure are commonly used in
      epidemiological studies, especially when financial and logistical resources are
      limited. However, self-reporting is prone to misclassification bias. This pilot
      study assesses the agreement between self-report of residential pesticide
      exposure with direct observation measures, in an agricultural region of Ecuador,
      as a cross-validation method in 26 participants (16 rose workers and 10
      controls), with percent agreement and kappa statistics calculated. Proximity of
      homes to nearby flower farms was found to have only fair agreement (kappa =.35).
      The use of discarded plastics (kappa =.06) and wood (kappa =.13) were found to
      have little agreement. Results indicate that direct observation or measurement
      may provide more accurate appraisals of residential exposures, such as proximity
      to industrial farmland and the use of discarded materials obtained from the
      flower farms. 

PMID- 24455981
TI  - Phase transition of a quaternary ammonium Gemini surfactant induced by minor
      structural changes of protic ionic liquids.
AB  - The aggregation behaviors of a Gemini surfactant
      [C12H25(CH3)2N(+)(CH2)2N(+)(CH3)2C12H25]Br2(-) (12-2-12) in two protic ionic
      liquids (PILs), propylammonium nitrate (PAN) and butylammonium nitrate (BAN),
      were investigated by means of several experimental techniques including small and
      wide-angle X-ray scattering, the polarized optical microscopy and the rheological
      measurement. Compared to those in ethylammonium nitrate (EAN), the minor
      structural changes with only one or two methylene units (-CH2-) increase in
      cationic chain length of PIL, result in a dramatic phase transition of formed
      aggregates. The critical micellization concentration was increased in PAN, while
      no micelle formation was detected in BAN. A normal hexagonal phase was observed
      in the 12-2-12/PAN system, while the normal hexagonal, bicontinuous cubic, and
      lamellar phases were mapped in the 12-2-12/BAN system. Such aggregation behavior
      changes can be ascribed to the weaker solvophobic interactions of 12-2-12 in PAN
      and BAN. The unique molecular structure of 12-2-12 is also an important factor to
      highlight such a dramatic phase transition due to the PIL structure change. 

PMID- 24455980
TI  - Determination of adrenal volume by MRI in healthy children: associations with
      age, body size, pubertal stage and serum levels of adrenal androgens.
AB  - BACKGROUND: Adrenal disorders such as congenital adrenal hyperplasia result in
      abnormal adrenal size and morphology, but little is known about the clinical
      value of magnetic resonance imaging (MRI) in determining adrenal volume.
      OBJECTIVE: To evaluate the potential usefulness of MR methodology, to estimate
      adrenal size in healthy children and to evaluate determinants of adrenal volume
      such as age, gender, body size, pubic hair stage and serum levels of adrenal
      androgens. DESIGN: Two hundred and thirty-five healthy children (116 girls and
      119 boys) (age range 10.0-14.8 years) were examined by MRI. Clinical examinations
      (anthropometry and pubertal staging) were performed, and five androgen
      metabolites were measured in blood samples by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). RESULTS: It was possible to determine adrenal volume in
      115/235 children using MRI. The adrenals were not measurable in 51% of children
      due to breathing and moving artefacts. The median volume of the right adrenal
      gland was 0.46 ml in girls and 0.46 ml in boys. The median volume of the left
      adrenal gland was 0.34 ml in girls and 0.40 ml in boys. Adrenal size was
      positively associated with body surface area (estimate B = 0.34 ml/year, P =
      0.03), age (estimate B = 0.05 ml/year, P = 0.021) and pubic hair stage (estimate
      B = 0.05 ml/stage, P = 0.075). No associations between adrenal size and serum
      levels of adrenal androgens were observed. CONCLUSION: It was possible to
      determine adrenal volume by MRI in only 50% of healthy children aged 10-15 years.
      Adrenal volume increased with age and Tanner stage of pubic hair. Future studies
      will unravel whether adrenal MRI is useful when evaluating children with adrenal
      diseases.

PMID- 24455983
TI  - Black sexual politics: African Americans, gender, and the new racism.

PMID- 24455982
TI  - Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a
      comprehensive review.
AB  - The American Cancer Society estimates that 73 510 new cases of bladder cancer
      will be diagnosed and 15 000 deaths will result this year. The paper summarizes
      the clinical evidence for the use of platinum-based, non-platinum-based and new
      targeted biological agents, while reporting the future directions in the
      treatment of metastatic bladder cancer. For cisplatin-base regimens, the
      combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) has
      been the mainstream treatment for both advanced and metastatic bladder cancers.
      It showed significant improvement in the complete response rate and overall
      survival time in comparison with single-agent cisplatin. For cisplatin-ineligible
      patients, namely patients with renal impairment, symptomatic cardiac disease and
      poor performance status, alternative therapies consisting of paclitaxel,
      gemcitabine and carboplatin were shown to be of benefit. Pemetrexed and
      vinflunine have also shown effectiveness, with small but demonstrable overall
      survival benefits. Gemcitabine-based doublet therapies (combined with paclitaxel,
      docetaxel, irinotecan, oxaliplatin or epirubicin) have all been shown to be
      effective and well-tolerated. Several new targeted therapies, such as gefetinib,
      sorafenib and lapatinib, have received attention in recent years; however, their
      effectiveness as single agents in a relapse setting have not been optimal and
      more studies are warranted.

PMID- 24455984
TI  - Anti-inflammatory and chondroprotective activity of (+)-alpha-pinene: structural
      and enantiomeric selectivity.
AB  - Previous studies have suggested that alpha-pinene, a common volatile plant
      metabolite, may have anti-inflammatory effects in human chondrocytes, thus
      exhibiting potential antiosteoarthritic activity. The objective of this study was
      to further characterize the potential antiosteoarthritic activity of selected
      pinene derivatives by evaluating their ability to modulate inflammation and
      extracellular matrix remodeling in human chondrocytes and to correlate the
      biological and chemical properties by determining whether the effects are isomer-
      and/or enantiomer-selective. To further elucidate chemicopharmacological
      interactions, the activities of other naturally occurring monoterpenes with the
      pinane nucleus were also investigated. At noncytotoxic concentrations, (+)-alpha
      pinene (1) elicited the most potent inhibition of the IL-1beta-induced
      inflammatory and catabolic pathways, namely, NF-kappaB and JNK activation and the
      expression of the inflammatory (iNOS) and catabolic (MMP-1 and -13) genes. (-)
      alpha-Pinene (2) was less active than the (+)-enantiomer (1), and beta-pinene (3)
      was inactive. E-Pinane (4) and oxygenated pinane-derived compounds, pinocarveol
      (5), myrtenal (6), (E)-myrtanol (7), myrtenol (8), and (Z)-verbenol (9), were
      less effective or even completely inactive and more cytotoxic than the pinenes
      tested (1-3). The data obtained show isomer- and enantiomer-selective anti
      inflammatory and anticatabolic effects of alpha-pinene in human chondrocytes, (+)
      alpha-pinene (1) being the most promising for further studies to determine its
      potential value as an antiosteoarthritic drug. 

PMID- 24455985
TI  - Association of neutrophil-lymphocyte ratio with glucose intolerance: an indicator
      of systemic inflammation in patients with type 2 diabetes.
AB  - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been demonstrated to be a
      better risk factor than total white blood cell count in the prediction of adverse
      outcomes in various medical conditions. This study analyzed the association of
      NLR with different grades of glucose tolerance and insulin resistance in Asian
      Indians. SUBJECTS AND METHODS: Study subjects were recruited from Phase 3 of the
      Chennai Urban Rural Epidemiology Study (CURES). For this cross-sectional
      analysis, subjects with normal glucose tolerance (NGT) (n=237), impaired glucose
      tolerance (IGT) (n=63), and type 2 diabetes mellitus (DM) (n=286) were selected.
      The hemogram was done in all subjects using a five-part hematology analyzer
      (model SF-3000; Sysmex, Kobe, Japan). The NLR was calculated as the ratio between
      counts for neutrophils and total lymphocytes. Fasting insulin was measured by
      enzyme-linked immunosorbent assay, and insulin resistance was calculated using
      the homeostasis model assessment (HOMA-IR). RESULTS: Subjects with DM showed a
      significantly higher NLR (2.2 +/- 1.12) compared with IGT subjects (1.82 +/-
      0.63), who in turn had a higher ratio than NGT subjects (1.5 +/- 0.41) (P<0.01).
      Pearson correlation analysis showed a significant positive correlation of NLR
      with glycated hemoglobin (r=0.411), fasting plasma glucose (r=0.378), and HOMA-IR
      (r=0.233) (P<0.001). Regression analysis showed a linear increase in NLR with
      increasing severity of glucose intolerance even after adjusting for age, waist
      circumference, blood pressure, triglycerides, and smoking. CONCLUSIONS: This is
      the first report on the correlation of NLR with different grades of glucose
      intolerance and insulin resistance. NLR can be used as an adjuvant prognostic
      marker for macro- and microvascular complications in patients with glucose
      intolerance.

PMID- 24455986
TI  - Harvard Catalyst | The Clinical Translational Science Center IND/IDE Consult
      Service: providing an IND/IDE consult service in a decentralized network of
      academic healthcare centers.
AB  - The Food and Drug Administration (FDA) regulations require sponsors of clinical
      investigations involving an investigational drug or device to submit an
      Investigational New Drug (IND) or Investigational Device Exemption (IDE)
      application. Strict adherence to applicable regulations is vital to the success
      of clinical research. Unlike most major pharmaceutical sponsors, investigator
      sponsors often do not fully appreciate their regulatory obligations nor have
      resources to ensure compliance. As a result they can place themselves and their
      institutions at risk. Nevertheless, investigator-initiated clinical trials are
      vital to the further development of innovative drugs, biologics, and medical
      devices. The IND/IDE Subcommittee under the Regulatory Knowledge and Support
      Program at Harvard Catalyst, The Harvard Clinical and Translational Science
      Center worked in collaboration with Harvard and Harvard affiliated institutions
      to create and launch an IND/IDE Consult Service in a decentralized network of
      collaborating Academic Healthcare Centers (AHC). The IND/IDE Consult Service
      offers expertise, resources, and shared experiences to assist sponsor
      investigators and IRBs in meeting regulatory requirements for conducting and
      reviewing investigator-initiated IND/IDE studies. The scope of the services
      provided by the Harvard Catalyst IND/IDE Consult Service are described, including
      the specifics of the service, lessons learned, and challenges faced, in a
      scalable model that builds inter-institutional capacity. 

PMID- 24455989
TI  - Implant Treatments for Edentulous Maxilla With Anterior Hyperfunction.

PMID- 24455990
TI  - Fluorination effects on the shapes of complexes of water with ethers: a
      rotational study of trifluoroanisole-water.
AB  - The rotational spectra of five isotopologues of the 1:1 complex trifluoroanisole
      water have been investigated with pulsed jet Fourier transform microwave
      spectroscopy. The triple fluorination of the methyl group greatly affects the
      features of the rotational spectrum of the complex with water, with respect to
      those of the related complex anisole-water. The shape, the internal dynamics, and
      the isotopic effects turned out to be quite different from those of the anisole
      water adduct ( Giuliano , B. M. ; Caminati , W. Angew. Chem., Int. Ed. 2005 , 44
      , 603 - 606 ). However, as in anisole-water, water has the double role as a
      proton donor and proton acceptor, and it is linked to trifluoroanisole through
      two, O-H...O and C-H...O hydrogen bonds. 

PMID- 24455991
TI  - Nanofiber-expanded human umbilical cord blood-derived CD34(+) cell therapy
      accelerates cutaneous wound closure in NOD/SCID mice.
AB  - Nanofiber-expanded human umbilical cord blood-derived CD34(+) cell therapy has
      been shown to have potential applications for peripheral and myocardial ischaemic
      diseases. However, the efficacies of expanded CD34(+) cell therapy for treating
      cutaneous wounds and its mechanisms of action have yet to be established. Using
      an excisional wound model in non-obese diabetic/severe combined immune deficient
      mice, we show herein that CD34(+) cells accelerate the wound-healing process by
      enhancing collagen synthesis, and increasing fibroblast cell migration within the
      wound bed. Concomitantly, reduced levels of matrix metalloproteinase (MMPs) such
      as MMP1, MMP3, MMP9 and MMP13 were detected in the wound beds of animals treated
      with CD34(+) cells compared with vehicle-treated controls. CD34(+) cells were
      found to mediate enhanced migration and proliferation of dermal fibroblast cells
      in vitro. Moreover, CD34(+) cells secrete collagen in a serum-deprived
      environment. In mechanistic studies, co-culture of CD34(+) cells with primary
      skin fibroblasts increased the expression of collagen1A1, a component of type 1
      collagen, and decreased the expression of MMP1 in fibroblast cells in the
      presence of a proteasome inhibitor. Finally, CD34(+) cell-mediated functions were
      transcriptionally regulated by the c-Jun N-terminal kinases pathway.
      Collectively, these data provide evidence of therapeutic efficacy and a novel
      mechanism of nanofiber-expanded CD34(+) cell-mediated accelerated wound healing. 

PMID- 24455992
TI  - A new pharmacological role for donepezil: attenuation of morphine-induced
      tolerance and apoptosis in rat central nervous system.
AB  - BACKGROUND: Tolerance to the analgesic effect of opioids is a pharmacological
      phenomenon that occurs after their prolonged administration. It has been shown
      that morphine-induced tolerance is associated with apoptosis in the central
      nervous system and neuroprotective agents which prevented apoptosis signaling
      could attenuate tolerance to the analgesic effects. On the other hand donepezil,
      an acetylcholinesterase inhibitor, has been reported to have neuroprotective
      effects. Therefore in this study, the effect of systemic administration of
      donepezil on morphine-induced tolerance and apoptosis in the rat cerebral cortex
      and lumbar spinal cord was evaluated. Various groups of rats received morphine
      (ip) and different doses of donepezil (0, 0.5, 1, 1.5 mg/kg/day). Nociception was
      assessed using tail flick apparatus. Tail flick latency was recorded when the rat
      shook its tail. For apoptosis assay other groups of rats received the above
      treatment and apoptosis was evaluated by in situ terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. RESULTS: The
      results showed that administration of donepezil (0.5, 1, 1.5 mg/kg, ip) delayed
      the morphine tolerance for 9, 12 and 17 days, respectively. Furthermore
      pretreatment injection of donepezil attenuated the number of apoptotic cells in
      the cerebral cortex and lumbar spinal cord compared to the control group.
      CONCLUSION: In conclusion, we found that systemic administration of donepezil
      attenuated morphine-induced tolerance and apoptosis in the rat cerebral cortex
      and lumbar spinal cord.

PMID- 24455993
TI  - Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows
      early diagnosis of cardiac involvement in patients with transthyretin-derived
      systemic amyloidosis.
AB  - OBJECTIVE: To assess the usefulness of bone scintigraphy with (99m)Technetium
      hydroxymethylene diphosphonate ((99m)Tc-HDP) for the detection of cardiac
      involvement in a group of patients with ATTR amyloidosis in different phases of
      disease, to relate the findings to echocardiography, ECG and cardiac biomarkers,
      and to evaluate different bone scintigraphic techniques and calculation methods
      for quantification of the cardiac uptake and for correlation with
      echocardiographic features and cardiac biomarkers. METHODS: Forty-one patients
      underwent clinical examinations, echocardiography, ECG, measurement of cardiac
      biomarkers and bone scintigraphy (planar imaging and SPECT-CT) and were
      subsequently subdivided into three groups: (1) carriers of an amyloidogenic TTR
      mutation, n = 11, (2) proven ATTR amyloidosis without echocardiographically
      defined (mean wall thickness >12 mm) cardiac amyloidosis (AC), n = 19, and (3)
      ATTR amyloidosis with echocardiographically-defined cardiac amyloidosis, n = 11.
      Planar and SPECT-CT images were analyzed visually according to a routine scoring
      system (grade 0-3) and semi-quantitatively by heart-to-whole body (H/WB) and
      heart-to-skull (H/S) ratio on planar images and by a left ventricle-blood pool
      ratio on SPECT-CT images. RESULTS: All patients with ATTR and
      echocardiographically-defined AC and none of the carriers showed high cardiac
      uptake on bone scintigraphy. Furthermore, 8 out of 19 patients with ATTR without
      echocardiographically-defined AC showed high cardiac uptake. Highest correlations
      were found between H/S ratio on planar bone scintigraphy with troponin T (r =
      0.76, p < 0.0001) and H/WB ratio with left ventricular mass index (r = 0.73, p <
      0.0001). CONCLUSIONS: Bone scintigraphy with (99m)Tc-HDP may detect cardiac
      involvement in patients with ATTR amyloidosis prior to echocardiographic evidence
      of cardiac involvement. Cardiac uptake on bone scintigraphy correlates with
      severity of cardiac involvement using echocardiography, ECG and cardiac
      biomarkers. Visual grading and calculation of H/S ratio on planar imaging are the
      preferred methods to assess cardiac uptake.

PMID- 24455994
TI  - Aminoglycoside toxicity in neonates: something to worry about?
AB  - Toxicity has limited the use of aminoglycosides and adult studies report high
      rates of both ototoxicity and nephrotoxicity. Conversely paediatric studies have
      shown lower rates and extended interval dosing may have reduced toxicity further.
      We review the animal and human evidence for aminoglycoside toxicity in neonates
      including mechanisms, measurement and rates of toxicity; and differences between
      aminoglycosides and dosing regimens. We discuss genetic susceptibility and the
      impact of other synergistic effects. 

PMID- 24455995
TI  - Statistical analysis of causes of death (2005-2010) in villages of Simav Plain,
      Turkey, with high arsenic levels in drinking water supplies.
AB  - The purpose of this research was to compare the causes of death in 5 villages
      situated in Simav Plain, Turkey, during 2005-2010 where different arsenic levels
      were detected in drinking water supplies. Since groundwater in Simav Plain had
      arsenic concentrations that ranged between 7.1 and 833.9 ppb, a two-phase
      research was formulated. In the first phase, public health surveys were conducted
      with 1,003 villagers to determine the distribution of diseases. In the second
      phase, verbal autopsy surveys and official death records were used to investigate
      the causes of death. In total, 402 death cases were found in the study area where
      cardiovascular system diseases (44%) and cancers (15.2%) were major causes.
      Cancers of lung (44.3%), prostate (9.8%), colon (9.8%), and stomach (8.2%) were
      comparably higher in villages with high arsenic levels in drinking water
      supplies. Furthermore, the majority of cases of liver, bladder, and stomach
      cancers were observed in villages with high arsenic levels. 

PMID- 24455996
TI  - Misoprostol treatment for early pregnancy failure does not impair future
      fertility.
AB  - AIMS: To examine whether misoprostol treatment for first trimester missed
      abortion affects future fertility. PATIENTS AND METHODS: In a historical
      prospective approach, we analyzed our database for patients treated with
      misoprostol. All eligible patients underwent an interview according to a
      questionnaire, which includes their demographic characteristics, obstetric,
      gynecologic and infertility history. They were asked about the side effects,
      intention and subsequent ability to conceive. Their future pregnancy rates were
      calculated and compared to the acceptable figures in the literature. RESULTS: The
      infertility rates among our patients were similar to those reported in the
      general population. Pregnancy rates 2 years after treatment were similar to the
      previously published reports, except for lower rates during the first three
      months post-treatment. Although no between-group differences were observed in the
      subsequent pregnancy rates, 2 years following misoprostol treatment in <=35
      versus >35 years old patients, primi- versus multigravida and nulli- versus
      parous women, higher pregnancy rates were observed in patients <=35 versus >35
      years old, primi- versus multigravida and nulli- versus, parous, during the first
      3 months following misoprostol treatment. CONCLUSION: Misoprostol treatment, for
      women with first trimester missed abortion and favorable reproductive history, is
      an acceptable treatment with no detrimental effect on future fertility.

PMID- 24455998
TI  - Design of novel miconazole nitrate transdermal films based on Eudragit RS100 and
      HPMC hybrids: preparation, physical characterization, in vitro and ex vivo
      studies.
AB  - The objective of this study was to formulate and evaluate transdermal films
      containing miconazole nitrate (MN), a poorly water-soluble imidazole antifungal
      agent, with a view to enhancing its delivery across intact skin. Transdermal
      films of MN were formulated by solvent casting technique using admixtures of film
      forming polymers - Eudragit RS100 and hydroxypropylmethylcellulose (HPMC) (2:8,
      4:6, 5:5, 6:4 and 8:2) with polyethylene glycol 8000 (plasticizer and permeation
      enhancer) and Tween 80 (mobile surfactant). The films were evaluated for weight
      uniformity, folding endurance, thickness, moisture loss and uptake, bioadhesive
      strength, drug content, skin irritation on rabbits and time-resolved stability.
      The ex vivo release of MN from the films was carried out using a modified Franz
      diffusion apparatus while the microbiological evaluation was conducted using a
      clinical isolate of Candida albicans. Overall results indicate that films made
      with two portions of Eudragit RS100 and eight portions of HPMC (batch T-1) had
      the least weight variation (57.33 +/- 0.27 mg), folding endurance (307.90 +/-
      4.17), moisture uptake (1.37 +/- 0.28%) and thickness (145.9 +/- 2.08 um), but
      highest drug content (97.50 +/- 2.43%) and bioadhesive strength (81.40 +/- 2.03
      dyne/cm2), best bioactivity and in vitro skin permeation through rat skin with
      highest permeation flux (5.161 ug/cm2 h) and permeation coefficient (1.032 * 10-6
      cm/h) compared to all other formulations. This study has established that
      transdermal films based on 2:8 admixtures of Eudragit RS100 and HPMC could offer
      a promising approach for the treatment of skin infections caused by MN
      susceptible fungi.

PMID- 24456000
TI  - Nutritional status in stage V dialyzed patient versus CKD patient on conservative
      therapy across different economic status.
AB  - BACKGROUND: This aim of this multi-centric cross-sectional study was to assess
      the nutritional status in Indian chronic kidney disease (CKD) patients and to
      compare the nutritional indicators between stage 5 dialyzed (CKD-D) patients
      below the poverty line (BPL), and stage 3-4 non-dialyzed (CKD-ND) patients above
      (APL) and below the poverty line. METHODS: Patients were selected from a
      government medical college hospital, a charity-based outpatient dialysis unit,
      and a non-profit tertiary care center. The study groups included BPL CKD-ND (n =
      100), BPL CKD-D (n = 98), and APL CKD-ND (n = 92) patients, based on a cut-off of
      per capita income US $1.25 a day. Patients were enquired by a qualified renal
      dietitian about their pattern of diet, and daily energy and protein intake by 24
      h recall method. Anthropometric measurements and biochemical investigations were
      made and compared. RESULTS: Nutritional indicators were low in all three groups
      compared to those prescribed by European Best Practice Guidelines (EBPG). BPL CKD
      D patients had low serum albumin levels (32.44444 +/- 6.279961 g/L; p = 0.017)
      and 41.83% of them were underweight. The APL CKD-ND group registered the lowest
      mean daily energy (22.576 +/- 6.289 kcal/kg/day) and protein intake (0.71 +/-
      0.06 g/kg/day), due to dietary restrictions imposed on them by themselves and
      unqualified renal dietitians. The APL group had better indicators of nutritional
      status in terms of mid-upper arm circumference (p = 0.001), triceps skin fold
      thickness (p < 0.001), and serum hemoglobin (p < 0.001). CONCLUSION: Several
      nutritional parameters were below the recommended international guidelines for
      all the three groups, though the high income group had better parameters from
      several indicators. There is an urgent need for nutritional counseling for CKD-D
      and CKD-ND patients.

PMID- 24456001
TI  - Peri-Implant Plastic Surgical Approaches to Increasing Keratinized Mucosa Width.
AB  - The long-term efficacy of adequate keratinized mucosa (>2 mm) in dental implants
      is controversial. Peri-implant plastic surgeries are currently used because they
      increase keratinized mucosa width (KMW), helping to regain peri-implant health
      and maintaining it over the long-term. We present the clinical findings using
      free-gingival-graft (FGG) and free-periosteal-graft (FPG) techniques in peri
      implant plastic surgery for implant rehabilitation patients. We included 20
      patients with implant indications of inadequate KMW (KMW < 2 mm for
      postimplantation) in the maxilla and mandible. All underwent clinical and
      radiographic measurements and a treatment protocol was prepared for implant
      rehabilitation and subsequent peri-implant plastic surgery. A decision as to
      whether and when FGG or FPG techniques would be used was made. FGG/FPG was
      performed pre-implantation (before monocortical block-bone augmentation) or
      postimplantation (before/during/after stage 2 surgery). KMW was >= 2 mm after
      application of FGG/FPG pre- or post-implantation. Moreover, peri-implant tissue
      health was regained/maintained in all cases from 6 months to 4 years. Peri
      implant plastic surgery techniques can prevent hard- and soft-tissue problems
      after implant rehabilitation and during treatment of developing problems.
      However, surgical design and timing, and an interdisciplinary perspective
      determine the success of peri-implant plastic surgery. 

PMID- 24456003
TI  - CITED2 mutation and methylation in children with congenital heart disease.
AB  - BACKGROUND: The occurrence of Congenital Heart Disease (CHD) is resulted from
      either genetic or environmental factors or the both. The CITED2 gene deletion or
      mutation is associated with the development of cardiac malformations. In this
      study, we have investigated the role of CITED2 gene mutation and methylation in
      the development of Congenital Heart Disease in pediatric patients in China.
      RESULTS: We have screened 120 pediatric patients with congenital heart disease.
      Among these patients, 4 cases were detected to carry various CITED2 gene
      heterozygous mutations (c.550G > A, c.574A > G, c.573-578del6) leading
      correspondingly to the alterations of amino acid sequences in Gly184Ser,
      Ser192Gly, and Ser192fs, respectively. No CITED2 gene mutations were detected in
      the control group. At the same time, we found that CITED2 mutations could inhibit
      TFAP2c expression. In addition, we have demonstrated that abnormal CITED2 gene
      methylation was detected in most of the tested pediatric patients with CHD, which
      leads to a decrease of CITED2 transcription activities. CONCLUSIONS: Our study
      suggests that CITED2 gene mutations and methylation may play an important role in
      the development of pediatric congenital heart disease.

PMID- 24456002
TI  - Human trabecular meshwork cells exhibit several characteristics of, but are
      distinct from, adipose-derived mesenchymal stem cells.
AB  - PURPOSE: To support the growing promise of regenerative medicine in glaucoma, we
      characterized the similarities and differences between human trabecular meshwork
      (HTM) cells and human mesenchymal stem cells (hMSCs). METHODS: HTM cells and
      hMSCs were phenotypically characterized by flow cytometry. Using quantitative
      polymerase chain reaction, the expression of myoc, angptl7, sox2, pou5f1, and
      notch1 was determined in both cell types with and without dexamethasone (Dex).
      Immunosuppressive behavior of HTM cells and hMSCs was determined using T cells
      activated with phytohemagglutinin. T-cell proliferation was determined using BrdU
      incorporation and flow cytometry. Multipotency of HTM cells and hMSCs was
      determined using adipogenic and osteogenic differentiation media as well as
      aqueous humor (AH). Alpha-smooth muscle actin (alphaSMA) expression was
      determined in HTM cells, hMSCs, and HTM tissue. RESULTS: Phenotypically, HTM and
      hMSCs expressed CD73, CD90, CD105, and CD146 but not CD31, CD34, and CD45 and
      similar sox2, pou5f1, and notch1 expression. Both cell types suppressed T-cell
      proliferation. However, HTM cells, but not hMSCs, upregulated myoc and angptl7 in
      response to Dex. Additionally, HTM cells did not differentiate into adipocytes or
      osteocytes. Culture of hMSCs in 20%, but not 100%, AH potently induced alkaline
      phosphatase activity. HTM cells in culture possessed uniformly strong expression
      of alphaSMA, which contrasted with the limited expression in hMSCs and spatially
      discrete expression in HTM tissue. CONCLUSIONS: HTM cells possess a number of
      important similarities with hMSCs but lack multipotency, one of the defining
      characteristics of stem cells. Further work is needed to explore the molecular
      mechanisms and functional implications underlying the phenotypic similarities.

PMID- 24456004
TI  - Epigallocatechin 3-O-gallate induces 67 kDa laminin receptor-mediated cell death
      accompanied by downregulation of ErbB proteins and altered lipid raft clustering
      in mammary and epidermoid carcinoma cells.
AB  - Since the administration of synthetic medicines is associated with drug
      resistance and undesired side effects, utilization of natural compounds could be
      an alternative and complementary modality to inhibit or prevent the development
      of tumors. Epigallocatechin 3-O-gallate (EGCG, 1), the major flavan component of
      green tea, and genistein (2), a soy isoflavonoid, are known to have
      chemopreventive and chemotherapeutic effects against cancer. This study
      demonstrated that both flavonoids inhibit cell proliferation, an effect enhanced
      under serum-free conditions. Compound 1, but not 2, induced downregulation of
      ErbB1 and ErbB2 in mammary and epidermoid carcinoma cells, and its inhibitory
      effect on cell viability was mediated by the 67 kDa laminin receptor (67LR).
      While 1 was superior in inducing cell death, 2 was more efficient in arresting
      the tumor cells in the G2/M phase. Furthermore, number and brightness analysis
      revealed that 1 decreased the homoclustering of a lipid raft marker,
      glycosylphosphatidylinositol-anchored GFP, and it also reduced the co
      localization between lipid rafts and 67LR. The main conclusion made is that the
      primary target of 1 may be the lipid raft component of the plasma membrane
      followed by secondary changes in the expression of ErbB proteins. Compound 2, on
      the other hand, must have other unidentified targets. 

PMID- 24456005
TI  - Growth and proliferation of human embryonic stem cells on fully synthetic
      scaffolds based on carbon nanotubes.
AB  - Here we show an industrially scalable and inexpensive method of fabricating
      entirely synthetic, non-xenogeneic carbon nanotube-based scaffolds by vacuum
      filtration for the culture of human embryonic stem cells. We show that controlled
      exposure of carbon nanotubes to sonication and the amount of energy delivered to
      the dispersion directly impacts the surface properties, allowing for control over
      the nanotopography of the resulting carbon nanotube films, which in turn has
      demonstrable effects upon in vitro human embryonic stem cells cultures. By
      altering the nanotube processing conditions before film fabrication, it is
      possible to influence cell adherence, proliferation and colony morphology. Such a
      tunable surface with capabilities of influencing stem cell behaviors, combined
      with the ability to slow or speed population doubling times, will provide crucial
      solutions for achieving applications envisioned by stem cell biologists to assist
      future industrial and clinical implementation of human embryonic stem cells. 

PMID- 24456006
TI  - Bone reconstruction in rat calvarial defects by chitosan/hydroxyapatite
      nanoparticles scaffold loaded with unrestricted somatic stem cells.
AB  - Calcium phosphates are one of the biomaterials that are used for bone
      regeneration. In this study, Hydroxyapatite (HAp) nanoparticles with chitosan gel
      filled with unrestricted somatic stem cells (USSCs) were used for healing
      calvarial bone in rat model. The healing effects of these injectable scaffolds
      with and without stem cells for bone regeneration were investigated by computed
      tomography (CT) analysis and pathology assays after 28 days of grafting. The
      results of CT analysis showing bone regeneration on the scaffolds, also the
      amounts of regenerated new bone for USSC scaffold was significantly greater than
      the scaffold without cell and untreated controls. Therefore, the combination of
      scaffold especially with USSC is considered as a useful method for bone
      regeneration. 

PMID- 24456007
TI  - Superheavy element flerovium (element 114) is a volatile metal.
AB  - The electron shell structure of superheavy elements, i.e., elements with atomic
      number Z >= 104, is influenced by strong relativistic effects caused by the high
      Z. Early atomic calculations on element 112 (copernicium, Cn) and element 114
      (flerovium, Fl) having closed and quasi-closed electron shell configurations of
      6d(10)7s(2) and 6d(10)7s(2)7p1/2(2), respectively, predicted them to be noble-gas
      like due to very strong relativistic effects on the 7s and 7p1/2 valence
      orbitals. Recent fully relativistic calculations studying Cn and Fl in different
      environments suggest them to be less reactive compared to their lighter
      homologues in the groups, but still exhibiting a metallic character. Experimental
      gas-solid chromatography studies on Cn have, indeed, revealed a metal-metal bond
      formation with Au. In contrast to this, for Fl, the formation of a weak bond upon
      physisorption on a Au surface was inferred from first experiments. Here, we
      report on a gas-solid chromatography study of the adsorption of Fl on a Au
      surface. Fl was produced in the nuclear fusion reaction (244)Pu((48)Ca, 3
      4n)(288,289)Fl and was isolated in-flight from the primary (48)Ca beam in a
      physical recoil separator. The adsorption behavior of Fl, its nuclear alpha-decay
      product Cn, their lighter homologues in groups 14 and 12, i.e., Pb and Hg, and
      the noble gas Rn were studied simultaneously by isothermal gas chromatography and
      thermochromatography. Two Fl atoms were detected. They adsorbed on a Au surface
      at room temperature in the first, isothermal part, but not as readily as Pb and
      Hg. The observed adsorption behavior of Fl points to a higher inertness compared
      to its nearest homologue in the group, Pb. However, the measured lower limit for
      the adsorption enthalpy of Fl on a Au surface points to the formation of a metal
      metal bond of Fl with Au. Fl is the least reactive element in the group, but
      still a metal. 

PMID- 24456008
TI  - Ambient and Personal Effective Dose Assessment at the International Arrival Hall
      of Taichung Airport in Taiwan.
AB  - Ambient monitor and phantom studies were carried out in the international arrival
      hall of Taichung Airport, Taiwan. A total of 172 thermoluminescent dosimeters
      (TLDs) were used for ambient monitoring. The sites of the export conveyor, the
      outward face of the x-ray scanning chamber, and the x-ray image monitor were
      assessed as low-radiation areas because the possible annual effective doses were
      0.12, 0.39, and 0.16 mSv, all less than 1 mSv per year. In addition, a phantom
      filled with 126 TLDs was used to simulate a 10-year-old child being exposed by
      the x-ray baggage scanner. The effective dose was evaluated as 3.39 +/- 0.33
      MUSv/scan, using the tissue weighting factor of the International Commission on
      Radiological Protection (ICRP) 103 report. This figure is a useful reference
      should a person be accidentally scanned by the x-ray baggage scanner.

PMID- 24456009
TI  - Streptococcus pyogenes cervical intertrigo with secondary bacteremia.
AB  - We report a 12-month-old infant girl with cervical intertrigo caused by
      Streptococcus pyogenes. This form of intertrigo has been reported in only five
      children, but it is clearly underestimated. It should be suspected for well
      demarcated beefy-red lesions of the neck not responding to antifungal therapy. A
      rapid streptococcal antigen test of a lesion specimen is a useful diagnostic
      tool. Our patient was notable for the development of S. pyogenes bacteremia, a
      complication that has not been previously associated with this condition.

PMID- 24456012
TI  - Single-Tray Impression Technique for Implant-Supported Overdentures.

PMID- 24456011
TI  - Safety of a liberal policy for extended-date preadmission testing samples.
AB  - BACKGROUND: Regulations governing pretransfusion testing allow specimen
      expiration to be extended past 3 days before the transfusion if a patient has not
      been transfused or pregnant in the preceding 3 months. Our hospital allows
      extension of the expiration of a presurgical specimen to 28 days if 1) the
      patient has neither been transfused nor pregnant in the past 3 months, 2) the
      patient does not have an antibody history, and 3) the current antibody screen
      (ABSC) is negative. Patients not meeting Criteria 2 and 3 are required to have
      specimens redrawn on the day of surgery (DOS). We evaluated the necessity of this
      policy. STUDY DESIGN AND METHODS: From October 2009 to September 2010, there were
      132 patients who did not meet the above criteria for specimen extension.
      Equivalent tests were performed on preadmission testing (PAT) and DOS specimens,
      and the results were compared. RESULTS: The majority (113, 86%) of the samples
      redrawn on the DOS showed no change in antibody serology upon reinvestigation. Of
      the remaining patients, DOS specimens did not identify any new antibodies or
      change in blood product choices. CONCLUSION: Of the PAT specimens rejected for
      antibody history or positive ABSC, none had new significant serologic findings on
      DOS. Based on these results, requiring a repeat specimen on the DOS may not be
      clinically necessary. Our facility changed the PAT policy to extend specimen
      acceptability to patients with red blood cell antibody history or positive ABSC
      at time of PAT. A 6-month follow-up period showed that this practice is safe.

PMID- 24456010
TI  - Reassortment patterns of avian influenza virus internal segments among different
      subtypes.
AB  - BACKGROUND: The segmented RNA genome of avian Influenza viruses (AIV) allows
      genetic reassortment between co-infecting viruses, providing an evolutionary
      pathway to generate genetic innovation. The genetic diversity (16 haemagglutinin
      and 9 neuraminidase subtypes) of AIV indicates an extensive reservoir of
      influenza viruses exists in bird populations, but how frequently subtypes
      reassort with each other is still unknown. Here we quantify the reassortment
      patterns among subtypes in the Eurasian avian viral pool by reconstructing the
      ancestral states of the subtypes as discrete states on time-scaled phylogenies
      with respect to the internal protein coding segments. We further analyzed how
      host species, the inferred evolutionary rates and the dN/dS ratio varied among
      segments and between discrete subtypes, and whether these factors may be
      associated with inter-subtype reassortment rate. RESULTS: The general patterns of
      reassortment are similar among five internal segments with the exception of
      segment 8, encoding the Non-Structural genes, which has a more divergent
      phylogeny. However, significant variation in rates between subtypes was observed.
      In particular, hemagglutinin-encoding segments of subtypes H5 to H9 reassort at a
      lower rate compared to those of H1 to H4, and Neuraminidase-encoding segments of
      subtypes N1 and N2 reassort less frequently than N3 to N9. Both host species and
      dN/dS ratio were significantly associated with reassortment rate, while
      evolutionary rate was not associated. The dN/dS ratio was negatively correlated
      with reassortment rate, as was the number of negatively selected sites for all
      segments. CONCLUSIONS: These results indicate that overall selective constraint
      and host species are both associated with reassortment rate. These results
      together identify the wild bird population as the major source of new
      reassortants, rather than domestic poultry. The lower reassortment rates observed
      for H5N1 and H9N2 may be explained by the large proportion of strains derived
      from domestic poultry populations. In contrast, the higher rates observed in the
      H1N1, H3N8 and H4N6 subtypes could be due to their primary origin as infections
      of wild birds with multiple low pathogenicity strains in the large avian
      reservoir.

PMID- 24456013
TI  - Effectiveness of the antagonist/letrozole protocol for treating poor responders
      undergoing in vitro fertilization/intracytoplasmic sperm injection: a systematic
      review and meta-analysis.
AB  - In view of the conflicting data regarding the efficacy of the gonadotropin
      releasing hormone (GnRH) antagonist/letrozole (A/L) protocol for treating poor
      responders undergoing in vitro fertilization/intracytoplasmic sperm injection
      (IVF/ICSI), this systematic review and meta-analysis aimed to compare the
      effectiveness of the A/L protocol and the microdose GnRH agonist flare up (MF)
      protocol for such treatment. MEDLINE, EMBASE, Web of Science, and the China
      National Knowledge Infrastructure were searched for studies comparing the A/L and
      MF protocols for treating poor responders undergoing IVF/ICSI. We retrieved
      reports of three trials with data for 688 cycles in women. The clinical pregnancy
      rate was significantly decreased with the A/L compared with MF protocol (RR 0.70;
      95% CI: 0.57-0.86; p = 0.001), the duration of gonadotrophin stimulation was
      lower with the A/L than MF protocol (MD -1.25; 95% CI: -2.37 to -0.12; p = 0.03).
      Moreover, there was no significant difference in cycle cancellation rate, number
      of oocytes retrieved, and the total dose of gonadotrophin between the two
      protocols. In conclusions, the clinical pregnancy rate may be lower with the A/L
      than MF protocol for treating poor responsers undergoing IVF/ICSI, but large
      scale randomised controlled trials are needed to assess the A/L protocol.

PMID- 24456015
TI  - Diagnosis and management of a maxillary lateral incisor exhibiting dens
      invaginatus and dens evaginatus.
AB  - This case report, involving an indigenous Australian, presents the diagnosis and
      non-surgical endodontic management of a 22 with developmental abnormalities. They
      include a dens evaginatus and a dens invaginatus that extends to an apical burst
      in a second truncated root. Cone-beam computed tomography and endodontic
      microscopy were not available to the clinician. This case report focuses on
      ambiguities appearing in the literature relating to classification and
      terminology associated with the abovementioned developmental anomalies. It also
      demonstrates the need to methodically collect and cautiously interpret available
      information before initiating endodontic intervention. Axial inclination,
      distance perception, internal demarcation and spatial awareness, together with an
      understanding of dental anatomy, embryology and histology and associated
      physiology and pathology, allowed the clinician to accurately predict the point,
      the angle and the depth of coronal access. Sensibility of the dentino-pulpal
      complex was maintained. Critical thinking, experience, innovation, problem
      solving and established principles can compensate for inaccessible technologies.

PMID- 24456017
TI  - Development of recalcitrant skin ulcers as a side-effect of treatment with
      topical 5% imiquimod cream: report of two cases.

PMID- 24456018
TI  - Studying the organization of genes encoding plant cell wall degrading enzymes in
      Chrysomela tremula provides insights into a leaf beetle genome.
AB  - The ability of herbivorous beetles from the superfamilies Chrysomeloidea and
      Curculionoidea to degrade plant cell wall polysaccharides has only recently begun
      to be appreciated. The presence of plant cell wall degrading enzymes (PCWDEs) in
      the beetle's digestive tract makes this degradation possible. Sequences encoding
      these beetle-derived PCWDEs were originally identified from transcriptomes and
      strikingly resemble those of saprophytic and phytopathogenic microorganisms,
      raising questions about their origin; e.g. are they insect- or microorganism
      derived? To demonstrate unambiguously that the genes encoding PCWDEs found in
      beetle transcriptomes are indeed of insect origin, we generated a bacterial
      artificial chromosome library from the genome of the leaf beetle Chrysomela
      tremula, containing 18 432 clones with an average size of 143 kb. After
      hybridizing this library with probes derived from 12 C. tremula PCWDE-encoding
      genes and sequencing the positive clones, we demonstrated that the latter genes
      are encoded by the insect's genome and are surrounded by genes possessing
      orthologues in the genome of Tribolium castaneum as well as in three other beetle
      genomes. Our analyses showed that although the level of overall synteny between
      C. tremula and T. castaneum seems high, the degree of microsynteny between both
      species is relatively low, in contrast to the more closely related Colorado
      potato beetle. 

PMID- 24456019
TI  - Comprehensive review on additives of topical dosage forms for drug delivery.
AB  - Skin is the largest organ of the human body and plays the most important role in
      protecting against pathogen and foreign matter. Three important modes such as
      topical, regional and transdermal are widely used for delivery of various dosage
      forms. Among these modes, the topical dosage forms are preferred because it
      provides local therapeutic activity when applied to the skin or mucous membranes.
      Additives or pharmaceutical excipients (non-drug component of dosage form) are
      used as inactive ingredients in dosage form or tools for structuring dosage
      forms. The main use of topical dosage form additives are controling the extent of
      absorption, maintaining the viscosity, improving the stability as well as
      organoleptic property and increasing the bulk of the formulation. The overall
      goal of this article is to provide the clinician with information related to the
      topical dosage form additives and their current major applications against
      various diseases.

PMID- 24456020
TI  - Readability and comprehensibility of over-the-counter medication labels.
AB  - Nonprescription medications are relatively safe, but not risk-free and can lead
      to serious adverse events, particularly if used contrary to directions or without
      attention to depicted warnings. The question arises whether the information
      presented on the product label is readable and comprehensible to the average lay
      person. We examined the product labels of nonprescription medications for
      readability and comprehensibility characteristics using the Flesch-Kincaid
      method. The Flesch-Kincaid reading ease scores and grade level scores were
      derived. We further validated the grade level scores using the Gunning-Fog
      method. Qualitative assessment of select labels found severe deficiencies such as
      poor organization and inundation with technical terms. By quantitative assessment
      the average reading ease score of 40 nonprescription medication labels (including
      nonsteroidal anti-inflammatory agents, antacids, laxative preparations, anti
      allergy medications, H-2 blockers, proton pump inhibitors, sleep aids, an
      antiasthmatic, and cough and cold remedies) was 38 +/- 12. The average Flesch
      Kincaid grade level score was 16 +/- 5. All labels except one were at reading
      grade level greater than the eighth grade. The average grade level of education
      necessary to understand the material according to the Gunning-Fog method was 17
      +/- 5 and all labels were above the eighth grade reading level. Nonprescription
      medication labels are written in a language that is not comprehensible to the
      average member of the general public. There is a need for considerable
      improvement in the readability of these labels.

PMID- 24456021
TI  - Formation of novel T-shaped NNN ligands via rare-earth metal-mediated Si-H
      activation.
AB  - Reactions of silylamides [Ln{N(SiHMe2)2}3(thf)2] with sterically crowded
      terphenylamine DmpNH2 (Dmp = 2,6-Mes2C6H3 with Mes = 2,4,6-Me3C6H2) afforded via
      a template reaction the formation of a new tridentate ligand, and derived
      complexes of composition [LnN{SiMe2N(Dmp)}2] (Ln = Ce, Pr) were obtained. Usage
      of the even more bulky amine Ar*NH2 (Ar* = 2,6-Trip2C6H3 with Trip = 2,4,6
      iPr3C6H2) yielded the free protonated ligand NH{SiMe2NH(Ar*)}2. 

PMID- 24456022
TI  - Calculation of aqueous solubility of crystalline un-ionized organic chemicals and
      drugs based on structural similarity and physicochemical descriptors.
AB  - Solubilities of crystalline organic compounds calculated according to AMP
      (arithmetic mean property) and LoReP (local one-parameter regression) models
      based on structural and physicochemical similarities are presented. We used data
      on water solubility of 2615 compounds in un-ionized form measured at 25+/-5 
      degrees C. The calculation results were compared with the equation based on the
      experimental data for lipophilicity and melting point. According to statistical
      criteria, the model based on structural and physicochemical similarities showed a
      better fit with the experimental data. An additional advantage of this model is
      that it uses only theoretical descriptors, and this provides means for
      calculating water solubility for both existing and not yet synthesized compounds.

PMID- 24456023
TI  - Breastfeeding barriers revisited.

PMID- 24456025
TI  - Layer-by-layer assembled oxidative films as general platform for electrodeless
      formation of conducting polymers.
AB  - Fabrication of precisely tailored layers of conductive polymers in thin film
      assemblies is an attractive extension of the layer-by-layer technique. This
      approach provides tools for fabricating thin films with customized optical and
      electrical properties. In this paper, we study inorganic layer-by-layer assembled
      films prepared using polyphosphate and cerium(IV). It is shown that these
      multilayers can oxidize certain monomers from the adjacent aqueous solution to
      produce conducting polymer layers. We studied the thermodynamic factors that
      allow the aforementioned autopolymerization. A five bilayer
      polyphosphate/cerium(IV) film was shown to possess high oxidative power in acidic
      solutions. It was found that the polymerization of pyrrole, aniline and 3,4
      ethylenedioxythiophene in contact with the redox active multilayer is
      thermodynamically favored. The rate of polymer formation and the thickness of the
      conducting film could be controlled by the concentration of the monomer in
      solution and the number of cerium/polyphosphate bilayers in the oxidative film.
      The oxidative polymerization of pyrrole was unambiguously recognized on UV-vis
      spectra with characteristic reduction and oxidation bands. The film formation was
      not restricted by charge diffusion and the reaction formally followed first-order
      kinetics. The results suggest that the reaction takes place effectively within
      the whole pre-existing polypyrrole film and it continues until all oxidant in the
      film was used. The spectral changes that are characteristic for conducting
      polypyrrole are shown on spectroelectrochemical analysis of the films indicating
      that cationic (polaron) and dicationic (bipolaron) species are involved in the
      redox processes of the film. The functional polymer films formed are found to be
      electroactive and conducting. Therefore, they fully resemble of conducting
      polymer films prepared using traditional electropolymerization. 

PMID- 24456024
TI  - ABM clinical protocol #2: Guidelines for hospital discharge of the breastfeeding
      term newborn and mother: "The going home protocol," revised 2014.
AB  - A central goal of The Academy of Breastfeeding Medicine is the development of
      clinical protocols for managing common medical problems that may impact
      breastfeeding success. These protocols serve only as guidelines for the care of
      breastfeeding mothers and infants and do not delineate an exclusive course of
      treatment or serve as standards of medical care. Variations in treatment may be
      appropriate according to the needs of an individual patient. 

PMID- 24456026
TI  - De novo sirolimus and reduced-dose tacrolimus versus standard-dose tacrolimus
      after liver transplantation: the 2000-2003 phase II prospective randomized trial.
AB  - We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared
      to standard-dose tacrolimus, after liver transplantation is safe, tolerated and
      efficacious. In an international multicenter, open-label, active-controlled
      randomized trial (2000-2003), adult primary liver transplant recipients (n=222)
      were randomly assigned immediately after transplantation to conventional-dose
      tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose:
      5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7
      ng/mL). The study was terminated after 21 months due to imbalance in adverse
      events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%,
      p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving
      sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein
      thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence
      of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of
      acute cellular rejection were similar between the two groups. Early use of
      sirolimus using a loading dose followed by maintenance doses and reduced-dose
      tacrolimus in de novo liver transplant recipients is associated with higher rates
      of graft loss, death and sepsis when compared to the use of conventional-dose
      tacrolimus alone.

PMID- 24456027
TI  - Mutational spectrum of the c1 inhibitor gene in a cohort of Italian patients with
      hereditary angioedema: description of nine novel mutations.
AB  - Hereditary angioedema (HAE) is an autosomal dominant disease due to mutations in
      the C1 inhibitor gene (C1NH) that affects protein synthesis (HAE type I) or
      function (HAE type II). In 45 subjects affected by HAE diagnosed through clinical
      features and C1 inhibitor deficiency from the south of Italy (38 with type I and
      7 with type II HAE), the whole C1NH coding region was screened for mutations by
      direct DNA sequencing. A severity score based on clinical manifestation, age at
      disease onset, and need for long-term prophylaxis was used to investigate
      possible genotype-phenotype correlations. A series of 22 different mutations was
      identified: nine missense (40.9%), five nonsense (22.7%), six frameshift (27.3),
      one small deletion (4.5%), and one splicing defect (4.5%). Nine C1NH mutations
      have not been previously described. No correlation was found between C1 inhibitor
      function level and severity score or age at first attack. Moreover, there was no
      correlation between different types of mutations and clinical phenotype. The
      number of different mutations identified highlights the heterogeneity of C1
      inhibitor deficiency and supports the hypothesis that HAE clinical phenotype is
      not strictly related to the type of mutation but rather depends on unknown
      factors. 

PMID- 24456028
TI  - Withanolides from Physalis hispida.
AB  - Nine new withanolides (1-9), withahisolides A-I, were isolated along with nine
      known compounds (10-18) from the aerial parts of Physalis hispida. The structures
      of 1-9 were elucidated through a variety of spectroscopic techniques, while the
      structures of 1 and 2 were confirmed by X-ray crystallographic analysis.
      Compounds 1-3 are the first withanolides with nonaromatic six-membered ring D
      moieties. In addition, withanolide 8 represents a novel withanolide skeleton due
      to the absence of a C-13-C-17 bond within the steroidal nucleus. 

PMID- 24456029
TI  - The importance of surveillance for informing pretravel medical advice: imported
      malaria in New Zealand 1997-2009.
AB  - Malaria has never been endemic in New Zealand, and all cases have been diagnosed
      in international travelers. In this paper, we describe malaria cases reported
      from 1997 to 2009 and discuss epidemiological changes compared to a previous
      report from 1980 to 1992. From 1997 to 2009, 666 malaria infections were
      reported, with 410 cases (61.6%) in travelers aged 20-39 and 133 (20%) in
      military personnel. Infections were caused by Plasmodium vivax in 436 cases
      (72.7%) and Plasmodium falciparum in 163 (27.2%). In the 533 civilians, common
      countries of infection were Papua New Guinea (24.4%), India (18.6%), the Solomon
      Islands (8.8%), and Indonesia (6.1%). Most common regions of malaria acquisition
      for civilians were Papua New Guinea and Western Pacific (39.8%), Africa (24.7%),
      Indian subcontinent (19.5%), and Southeast Asia (13.6%). Compared to a previous
      report of malaria in New Zealand from 1980 to 1992, regions of malaria
      acquisition have changed significantly, with a lower percentage of cases acquired
      from Papua New Guinea and Western Pacific (from 59.2% to 39.3%), and a higher
      percentage from Africa (from 8.6% to 21.3%). The ethnic groups affected also
      differ significantly between the two surveillance periods, with a reduction in
      the percentage of cases reported in Caucasians (from 80.8 to 45.9%) and an
      increase in cases in Indians (from 7.0 to 15.7%), Papua New Guineans and Pacific
      Islanders (from 5.2 to 16.9%), other Asians (from 2.3 to 5.6%), and Africans
      (from 0 to 8.5%). Common locations of malaria infection have evolved over time
      and probably reflect changing travel patterns of New Zealanders and the origins
      of visitors and immigrants. Therefore, local surveillance is important for
      informing pretravel advice by identifying vulnerable groups and common
      destinations for malaria infection, so that special attention on malaria
      prevention can be focused on travelers who are at highest risk. Ongoing
      surveillance is also essential for monitoring the evolving epidemiology of
      imported malaria over time.

PMID- 24456030
TI  - Estimating the transfusion transmission risk of Q fever.
AB  - BACKGROUND: The Q fever outbreaks in the Netherlands in 2007 to 2009 initiated
      discussion on the necessity of measures to prevent transmission through blood
      products. Risk assessments help transfusion regulators decide when and where
      measures are required. This study assesses the transfusion transmission (TT) risk
      of Q fever using the European Up-Front Risk Assessment Tool (EUFRAT) model. STUDY
      DESIGN AND METHODS: We estimated the number of Q fever infections in recipients
      during the 2007 to 2009 outbreaks' peaks using selected notification data;
      estimates are calculated from the probability of a donor being infected. We
      compared this probability to the prevalence of infection estimated from an
      independent donation testing study and using the Biggerstaff model. We also
      quantified the risk reduction by implementing measures such as donation testing
      and donor deferral. RESULTS: At the peak of the 2007, 2008, and 2009 outbreaks,
      there were an estimated 0.21, 0.96, and 1.59 recipients infected with Q fever,
      respectively. Between June 1, 2009, and January 31, 2010, the probability of a
      donor being infected with Q fever in the high-incidence areas was estimated at
      260 (95% confidence interval, 192-340) per 100,000 donors, consistent with
      results from the donation testing study. The EUFRAT estimates were also
      consistent with estimates from the Biggerstaff model. Scenario analyses showed
      that donation testing provided the largest risk reduction of various risk
      reduction strategies. CONCLUSION: The TT risk of Q fever during the 2007 to 2009
      outbreaks was small, a result that is consistent with results of other studies.
      EUFRAT can be applied successfully to support decision making during outbreaks.

PMID- 24456031
TI  - Influence of male hyperinsulinaemia on IVF outcome.
AB  - The IVF outcome of a group of hyperinsulinaemic men (group B) was compared with a
      group of IVF males with normal insulin levels (group A). The participating
      females in the study groups were younger than 38 years old, had blocked Fallopian
      tubes and/or endometriosis, had normal insulin levels and produced five or more
      ova on stimulation. The male participants in both groups were normozoospermic
      with motility above 50% and sperm morphology between 5 and 13% normal forms (G
      pattern according to Tygerberg strict criteria). The two groups did not differ
      statistically in terms of age or semen parameters (P = 0.39; P < 0.05).The group
      of men that presented with normal insulin levels had a higher fertilisation rate
      (79.15% versus 74.57%) and superior embryo quality on day 3 (55.77% versus
      50.39%) than the group that presented with hyperinsulinaemia, but these
      differences were not statistically significant (P = 0.28, P = 0.40; P < 0.05).
      The clinical pregnancy rate of the group with normal insulin was significantly
      higher than that of the hyperinsulinaemic group, 57.9% versus 31.8% respectively
      (P = 0.03). The results suggest that hyperinsulinaemia had a negative impact on
      IVF outcome and patients should be advised accordingly.

PMID- 24456032
TI  - X-autosome translocations in amenorrhoea: a report of a three way translocation
      from Indian population.
AB  - Chromosomal translocations have been reported in a number of women undergoing
      cytogenetic studies for amenorrhoea and gonadal dysgenesis. This study was taken
      up to emphasize the role of X chromosome and to know the frequency of X-autosomal
      translocations in women with amenorrhoea in Indian population. Cytogenetic
      analysis was carried out in 1567 subjects referred for amenorrhoea during the
      period 2002-2012. GTG-banding was performed from peripheral blood lymphocyte
      cultures to detect the chromosome abnormalities in all the cases. The karyotype
      results revealed 43.6% cases with chromosomal abnormalities (n = 683 of 1567
      cases). The X-autosomal translocations was found in 2.64% (n = 18 of 683 cases).
      The common chromosomes involved with X were chromosomes 2, 4, 14 and 20. The
      translocations involved both p and q arms of the X chromosome.The break point
      "q26" of X was observed in the majority of the cases. Two interesting cases are
      discussed: one with three way translocation and another with two translocations.
      A high number of primary amenorrhoea (PA) and secondary amenorrhoea (SA) cases
      were involved in X-auto translocation which clearly reveals that chromosomal
      analysis plays an important role in the evaluation of amenorrhoea.

PMID- 24456033
TI  - Biofunctionalized microfiber-assisted formation of intrinsic three-dimensional
      capillary-like structures.
AB  - OBJECTIVES: A vascular supply network is essential in engineered tissues >100-200
      MUm thickness. To control vascular network formation in vitro, we hypothesize
      that capillarization can be achieved locally by using fibers to position and
      guide vessel-forming endothelial cells within a three-dimensional (3D) matrix.
      MATERIALS AND METHODS: Biofunctionalization of poly-(L-lactic acid) (PLLA) fibers
      was performed by amino-functionalization and covalent binding of RGD peptides.
      Human foreskin fibroblasts (HFFs) and human umbilical vein endothelial cells
      (HUVECs) were seeded on the fibers in a mould and subsequently embedded in fibrin
      gel. After 9-21 days of coculture, constructs were fixed and immunostained (PECAM
      1). Capillary-like structures with lumen in the 3D fibrin matrix were verified
      and quantified using two-photon microscopy and image analysis software. RESULTS:
      Capillary-like networks with lumen formed adjacent to the PLLA fibers. Increased
      cell numbers were observed to attach to RGD-functionalized fibers, resulting in
      enhanced formation of capillary-like structures. Cocultivation of HFFs
      sufficiently supported HUVECs in the formation of capillary-like structures,
      which persisted for at least 21 days of coculture. CONCLUSIONS: The guidance of
      vessel growth within tissue-engineered constructs can be achieved using
      biofunctionalized PLLA microfibers. Further methods are warranted to perform
      specified spatial positioning of fibers within 3D formative scaffolds to enhance
      the applicability of the concept.

PMID- 24456034
TI  - Racing pigeons: a reservoir for nitro-imidazole-resistant Trichomonas gallinae.
AB  - Trichomonas gallinae , the cause of avian trichomonosis, is most commonly found
      in the order Columbiformes. Racing pigeons are often treated preventively with
      nitro-imidazoles, which could result in the emergence of resistant isolates, and
      these isolates can be a threat to wildlife when exchanges occur. The sequence
      type of 16 T. gallinae isolates obtained from racing pigeons and 15 isolates from
      wild pigeons was determined based on the ITS1/5.8S rRNA/ITS2 region sequence. In
      addition, the resistance profiles of these isolates against 5 different nitro
      imidazoles (metronidazole, dimetridazole, ronidazole, tinidazole, and
      carnidazole) were determined. Two different Trichomonas sequence types were
      isolated. Sequence type A isolates were recovered from racing and wild pigeons,
      in contrast to sequence type B, which was only isolated from wild pigeons.
      Isolates with sequence type B were all susceptible to the tested nitro
      imidazoles, except for tinidazole resistance in 3 isolates. Resistance to the
      nitro-imidazoles was observed more frequently in isolates obtained from racing
      pigeons than from wild pigeons, with most isolates belonging to sequence type A.
      A higher percentage of the sequence type A isolated from racing pigeons, in
      comparison with those isolated from the wild pigeons, were resistant to the nitro
      imidazoles and displayed higher mean lethal concentration (MLC) values. Two
      isolates belonging to sequence type A, 1 recovered from a racing pigeon and 1
      from a wild pigeon, displayed a similar resistance pattern, suggesting a
      potential exchange of resistant isolates between racing pigeons and wild pigeons.

PMID- 24456035
TI  - Transient neonatal zinc deficiency due to a new autosomal dominant mutation in
      gene SLC30A2 (ZnT-2).
AB  - Transient neonatal zinc deficiency (TNZD) has a clinical presentation similar to
      that of acrodermatitis enteropathica but is caused by a low zinc concentration in
      maternal breast milk. TNZD becomes clinically evident during breastfeeding and is
      resolved by weaning and the introduction of complementary nutrition. We present a
      4-month-old girl with TNZD due to a new autosomal dominant mutation (663delC) in
      the maternal SLC30A2 gene not previously described in the literature. 

PMID- 24456036
TI  - C-Reactive protein and soluble intracellular adhesion molecule-1 are related to
      pulse wave reflection in type 1 diabetes 1C-1.
AB  - BACKGROUND: The association of inflammation with cardiovascular (CV)
      complications in diabetes remains a matter of considerable debate. Arterial
      stiffness and enhanced wave reflection play an important role in CV
      complications. Therefore, in the present study we investigated whether markers of
      inflammation are correlated with parameters of wave reflection in type 1 diabetes
      (T1D). METHODS: In all, 145 T1D patients were included in the study (median age
      32 years, disease duration 10 years, HbA1c 8.2%). Serum concentrations of high
      sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase (MMP)-9,
      soluble intracellular adhesion molecule-1 (sICAM-1), and myeloperoxidase (MPO)
      were estimated as markers of inflammation. Parameters of pulse wave reflection
      (central augmentation index [cAIx] and peripheral augmentation index [pAIx]) were
      assessed using pulse wave analysis. RESULTS: Multivariate linear regression
      analysis revealed that, after adjustment for age, mean blood pressure, HbA1c, low
      density lipoprotein-cholesterol, and the presence of at least one
      microangiopathic complication of diabetes, cAIx and pAIx were associated with
      serum concentration of hs-CRP (beta = 1.838, 95% confidence interval [CI] 0.336
      3.339 [P = 0.017]; and beta = 2.041, 95% CI 0.683-3.400 [P = 0.004],
      respectively) and sICAM-1 (beta = 0.073, 95% CI 0.015-0.131 [P = 0.014]; and beta
      = 0.066, 95% CI 0.013-0.119 [P = 0.016], respectively) in the study group.
      CONCLUSIONS: In T1D parameters of wave reflection are related to markers of
      inflammation.

PMID- 24456037
TI  - Charge invariant protein-water relaxation in GB1 via ultrafast tryptophan
      fluorescence.
AB  - The protein-water interface is a critical determinant of protein structure and
      function, yet the precise nature of dynamics in this complex system remains
      elusive. Tryptophan fluorescence has become the probe of choice for such dynamics
      on the picosecond time scale (especially via fluorescence "upconversion"). In the
      absence of ultrafast ("quasi-static") quenching from nearby groups, the TDFSS
      (time-dependent fluorescence Stokes shift) for exposed Trp directly reports on
      dipolar relaxation near the interface (both water and polypeptide). The small
      protein GB1 contains a single Trp (W43) of this type, and its structure is
      refractory to pH above 3. Thus, it can be used to examine the dependence of
      dipolar relaxation upon charge reconfiguration with titration. Somewhat
      surprisingly, the dipolar dynamics in the 100 fs to 100 ps range were unchanged
      with pH, although nanosecond yield, rates, and access all changed. These results
      were rationalized with the help of molecular dynamics (including QM-MM)
      simulations that reveal a balancing, sometimes even countervailing influence of
      protein and water dipoles. Interestingly, these simulations also showed the
      dominant influence of water molecules which are associated with the protein
      interface for up to 30 ps yet free to rotate at approximately "bulk" water rates.

PMID- 24456040
TI  - Comparison of a semiautomated hand-held device to test minimal erythema dose
      before narrowband ultraviolet B phototherapy with the conventional method using
      matched doses.
AB  - BACKGROUND: A semiautomated hand-held device has been introduced in some
      phototherapy centres to establish the minimal erythema dose (MED) before
      treatment with narrowband ultraviolet (NBUV) B. OBJECTIVES: To compare the
      semiautomated hand-held device with the conventional method of MED testing (a UV
      opaque template and a panel of UVB fluorescent tubes), using the same series of
      incremented doses. METHODS: Twenty-four patients referred for treatment with
      NBUVB phototherapy were included. Each patient had MED testing with the
      conventional method and the semiautomated hand-held device at the same level of
      the left and right back. The results were read by four investigators each time.
      RESULTS: The semiautomated hand-held device was a significant estimator of the
      MED using the conventional panel method (P < 0.001; r = 0.97). The average ratio
      of the hand-held MED to the conventional MED was 67%. The mean difference between
      the methods was 165 mJ/cm(2) . The interobserver test showed very high agreement
      for both methods of MED testing (Cronbach alpha coefficient 0.97 for the hand
      held MED tester vs. 0.93 for the conventional method). CONCLUSIONS: The
      semiautomated hand-held device MED results were lower than that of the
      conventional panel method and may prolong the treatment course by 2-3 treatments.
      The hand-held tester is a fast and reproducible method, and may allow more
      phototherapy units, limited by staff and time, to do MED testing.

PMID- 24456041
TI  - The demographics of the United States haemophilia treatment centre social
      workers: the results of a national survey.
AB  - Social Workers (SWs) are vital members of the multidisciplinary health care teams
      at Hemophilia Treatment Centers (HTCs) across the US. However, little research
      has been done to identify the demographics and qualifications of HTC SWs. In
      response to this lack of data, a subcommittee from the Social Work Working Group
      sponsored by the National Hemophilia Foundation conducted a national online
      survey in 2010. The authors attempted to ascertain the demographics and
      characteristics of SWs who work at HTCs across the country. The purpose of this
      article is to report the results of this online survey and evaluate the
      parameters of SW demographics in HTCs. Electronic surveys were sent to 143 HTC
      SWs. Ten were excluded and 100 were completed and returned, yielding a 75%
      response rate. The great majority of HTC SWs are women and almost half are middle
      aged (aged 40-59). They represent a highly educated, very experienced group of
      professionals. When asked why respondents stayed in their positions at the HTCs,
      answers appeared to highly correlate to factors related to the HTC
      multidisciplinary team model. The high survey response rate of 75% reflects the
      interest of HTC SWs in obtaining data that describe and quantify their
      qualifications. This information may serve as validation of the haemophilia SW
      role in times of funding cuts. It may also give a basis for the recruitment and
      retention of SWs in the haemophilia field. 

PMID- 24456043
TI  - Diurnal changes in electrocorticogram sleep slow-wave activity during development
      in rats.
AB  - According to the homeostatic regulation of sleep, sleep pressure accumulates
      during wakefulness, further increases during sleep deprivation and dissipates
      during subsequent sleep. Sleep pressure is electrophysiologically reflected by
      electroencephalogram slow-wave activity during non-rapid eye movement sleep, and
      is thought to be stable across time. During childhood and adolescence the brain
      undergoes massive reorganization processes. Slow-wave activity during these
      developmental periods has been shown in humans to follow an inverted U-shaped
      trajectory, which recently was replicated in rats. The goal of this study was to
      investigate in rats the diurnal changes of slow-wave activity during the inverted
      U-shaped developmental trajectory of slow-wave activity. To do so, we performed
      longitudinal electrocorticogram recordings, and compared the level of slow-wave
      activity at the beginning with the slow-wave activity level at the end of 24-h
      baselines in two sets of Sprague-Dawley rats. In younger animals (n = 17) we
      investigated specific postnatal days when overall slow-wave activity increases
      (postnatal day 26), peaks (postnatal day 28) and decreases (>postnatal day 28).
      The same analysis was performed in older animals (postnatal day 48, n = 6). Our
      results show a gain of slow-wave activity across 24 h on postnatal day 26,
      followed by no net changes on postnatal day 28, which was then followed by a loss
      of slow-wave activity during subsequent days (>postnatal day 28). Older animals
      did not show any net changes in slow-wave activity across 24 h. These results
      cannot be explained by differences in vigilance states. Thus, slow-wave activity
      during this developmental period may not only reflect the trajectory of sleep
      pressure but may additionally reflect maturational processes. 

PMID- 24456045
TI  - Supervised molecular dynamics (SuMD) as a helpful tool to depict GPCR-ligand
      recognition pathway in a nanosecond time scale.
AB  - Supervised MD (SuMD) is a computational method that allows the exploration of
      ligand-receptor recognition pathway investigations in a nanosecond (ns) time
      scale. It consists of the incorporation of a tabu-like supervision algorithm on
      the ligand-receptor approaching distance into a classic molecular dynamics (MD)
      simulation technique. In addition to speeding up the acquisition of the ligand
      receptor trajectory, this implementation facilitates the characterization of
      multiple binding events (such as meta-binding, allosteric, and orthosteric sites)
      by taking advantage of the all-atom MD simulations accuracy of a GPCR-ligand
      complex embedded into explicit lipid-water environment. 

PMID- 24456046
TI  - A comparative insight of potassium vanadates as positive electrode materials for
      Li batteries: influence of the long-range and local structure.
AB  - Potassium vanadates with ratio K/V = 1:3, 1:4, and 1:8, prepared by a fast and
      facile synthesis route, were investigated as positive electrode materials in
      lithium batteries. KV3O8 and K0.5V2O5 have layered structures, while K0.25V2O5
      exhibits a tunnel framework isomorphic to that of beta-Na0.33V2O5. The Raman
      spectra of KV3O8, K0.5V2O5, and K0.25V2O5 compounds are reported here for the
      first time, and a detailed comparative analysis distinguishes spectral patterns
      specific to each structural arrangement. The electrochemical performances of
      these potassium vanadates toward lithium insertion were investigated. The
      potassium-richer compound KV3O8 shows a good rechargeability in spite of a low
      discharge capacity of 70 mAh g(-1), while the potassium-poorer bronze K0.25V2O5
      exhibits the highest specific capacity of 230 mAh g(-1) but a slow and continuous
      capacity fade with cycling. We demonstrate that the K0.5V2O5 compound, with its
      double-sheet V2O5 layered framework characterized by a large interlayer spacing
      of 7.7 A, is the best candidate as positive electrode for lithium battery among
      the potassium-vanadium bronzes and oxides. A remarkable specific capacity of 210
      mAh g(-1), combined with excellent capacity retention, is achieved. 

PMID- 24456044
TI  - Preparation of multiple-unit floating-bioadhesive cooperative minitablets for
      improving the oral bioavailability of famotidine in rats.
AB  - Abstract The aims of this study were to prepare fine famotidine-containing
      floating-bioadhesive cooperative minitablets and to investigate the possibility
      of using those minitablets as a delivery system for promoting the oral
      bioavailability of famotidine. Nine minitablet formulations were designed using
      hydroxypropylmethylcellulose (HPMC K4M) as release-retarding polymers, Carbopol
      971P as bioadhesive materials and sodium bicarbonate (NaHCO3) as gas formers. The
      prepared 3 +/- 0.02 mm minitablets were evaluated in terms of their swelling
      ability, floating behavior, bioadhesion test and in vitro release. The optimized
      minitablets (F6) containing HPMC K4M (50.00%, w/w), Carbopol 971P (10.00%, w/w)
      and NaHCO3 (10.00%, w/w) were found to float in 1 min and remain lastingly
      buoyant over a period of 8 h in vitro, with excellent bioadhesive properties
      (20.81 g) and sustained drug release characteristics (T50% = 46.54%) followed one
      order model. In addition, plasma concentration-time profiles from pharmacokinetic
      studies in rats dosed with minitablets showed 1.62-fold (p < 0.05) increased
      absorption of famotidine, compared to the market tablets XinFaDing(r). These
      studies demonstrated that the multiple-unit floating-bioadhesive cooperative
      minitablets may be a promising gastro-retentive delivery system for drugs that
      play a therapeutic role in the stomach. 

PMID- 24456047
TI  - Multidrug resistance-associated protein (MRP1, 2, 4 and 5) expression in human
      corneal cell culture models and animal corneal tissue.
AB  - Preclinical studies addressing the transcorneal absorption of ophthalmic drugs
      are mainly performed using ex vivo animal corneas and in vitro corneal cell
      culture models, leaving open the question of transferability to humans in an in
      vivo situation. While passive drug absorption through corneal tissue is well
      understood, little is known about the expression of transporter proteins and
      active drug transport in human and animal corneas as well as corneal cell culture
      models. Therefore, the aim of this study was to conduct an expression analysis of
      four multidrug resistance-associated proteins (MRP1, 2, 4 and 5) in various in
      vitro and ex vivo corneal models, leading to a better understanding of the
      comparability of different corneal models regarding drug absorption and
      transferability to humans. Two well-established in vitro human corneal models,
      the HCE-T epithelial model and the more organotypic Hemicornea construct, both of
      which are based on the SV40 immortalized human corneal epithelial cell line HCE
      T, were analyzed, as were excised rabbit and porcine cornea. Specimens of abraded
      epithelia from human donor corneas were also tested. MRP mRNA expression was
      determined via reverse transcriptase polymerase chain reaction. Protein
      expression was examined using Western blot experiments and immunohistochemistry.
      The functional activity of the MRP efflux transporter was detected in transport
      assays using specific marker and inhibitor substances. The functional expression
      of all of the tested MRP transporters was detected in the HCE-T epithelial model.
      Hemicornea constructs displayed a similar expression pattern for MRP1, 4 and 5,
      whereas no MRP2 protein expression or activity was detected. However, excised
      animal corneas exhibited different expression profiles. In porcine cornea, no
      functional expression of MRP1, 2, or 5 was observed, and we failed to detect MRP4
      expression in rabbit cornea. The results suggest that MRP1, 2, 4, and 5 are
      expressed in the human corneal epithelium and confirm that the transfer of data
      obtained from animal experiments to an in vivo situation in humans should be
      performed with caution. 

PMID- 24456048
TI  - Crowding by anionic nanoparticles causes DNA double-strand instability and
      compaction.
AB  - Up to the present, DNA structural transitions caused by cationic polymers as well
      as in concentrated solutions of neutral polymers are well documented, while a
      little is known about DNA interaction with like-charge species. Herein, changes
      in the structure of DNA induced by anionic nanoparticles of different sizes (20
      130 nm) were investigated by combining single-molecule DNA fluorescent
      microscopy, to monitor the conformational dynamics of long-chain DNA, with
      spectroscopic methods, to gain insight into changes in the secondary structure of
      DNA. The results showed that several percent of negatively charged silica
      nanoparticles induced DNA compaction from a coil to a globule, and this change
      was accompanied by a decrease in the melting temperature of the DNA double helix.
      DNA was compacted into toroidal condensates with reduced diameters of about 20-30
      nm. Smaller 20 nm nanoparticles triggered a DNA coil-globule transition at lower
      concentrations, but the exclusion volume for each type of nanoparticle at the
      point of complete DNA collapse, as estimated by taking into account the depth of
      the ionic atmosphere, was found to be almost the same. 

PMID- 24456050
TI  - Evaluation of volume overload by bioelectrical impedance analysis, NT-proBNP and
      inferior vena cava diameter in patients with stage 3&4 and 5 chronic kidney
      disease.
AB  - BACKGROUND: Determination of fluid overload is important in chronic kidney
      disease. Early diagnosis and treatment of volume overload may decrease morbidity
      and mortality. We aimed to determine body composition by using bioelectrical
      impedance analysis, and studying other clinical characteristics, inferior vena
      cava diameter, and N-terminal pro-B natriuretic peptide associated with hydration
      status in chronic kidney disease Stages 3&4 and 5 in patients not undergoing
      dialysis. METHOD: We examined 62 patients with Stages 3&4 and 68 patients with
      Stage 5 chronic kidney disease. Plasma NT-proBNP was measured and analyzed after
      log transformation. Inferior vena cave diameter was measured with
      echocardiography and indexed for body surface area. Hydration status was assessed
      using multi-frequency bioelectrical impedance analysis. Overhydration was defined
      as overhydration/extracellular water >0.15. RESULTS: Overhydration was more
      frequent in Stage 5 than in Stages 3&4 patients. Systolic and diastolic blood
      pressure, inferior vena cava index, and log NT-proBNP were higher in overhydrated
      compared to non-overhydrated patients. A significant positive correlation existed
      between overhydration/extracellular water and log NT-proBNP, systolic and
      diastolic blood pressures, and inferior vena cava index. In multiple linear
      regression analysis, the variables associated with hydration status were male
      sex, extracellular water/total body water, and extracellular water/intracellular
      water (greater overhydration), while serum albumin levels had a negative
      association with overhydration. CONCLUSION: Overhydration is more prevalent in
      Stage 5 chronic kidney disease patients than in Stages 3&4 patients.
      Bioelectrical impedance analysis, inferior vena cava diameter, and NT-proBNP
      analysis in chronic kidney disease are useful methods to determine the volume
      overload.

PMID- 24456049
TI  - REFINE: a randomized trial comparing cyclosporine A and tacrolimus on fibrosis
      after liver transplantation for hepatitis C.
AB  - REFINE was a 12-month, prospective, open-label study in 356 patients receiving de
      novo liver transplantation for hepatitis C virus (HCV) cirrhosis, randomized to
      cyclosporine A (CsA) or tacrolimus with (i) no steroids, IL-2 receptor antibody
      induction and mycophenolic acid, or (ii) slow steroid tapering. The primary
      analysis population based on availability of liver biopsies comprised 165
      patients (88 CsA, 77 tacrolimus). There was no difference in the primary
      endpoint, fibrosis stage >=2 at 12 months, which occurred in 63/88 CsA-treated
      patients (71.6%) and 52/77 tacrolimus-treated patients (67.5%) (odds ratio [OR]
      1.11; 95% CI 0.56, 2.21; p = 0.759). Similarly, no significant between-group
      difference occurred at month 24 (OR 1.15; 95% CI 0.47, 2.80; p = 0.767). Among
      steroid-free patients, fibrosis score >=2 was significantly less frequent with
      CsA versus tacrolimus at month 12 (7/37 [18.9%] vs. 16/38 [42.1%]; p = 0.029).
      HCV viral load was similar in both the tacrolimus- and CsA-treated cohorts. Mean
      blood glucose was significantly higher with tacrolimus from day 15 onward. Biopsy
      proven acute rejection, graft loss and death were similar. These results showed
      no differences in posttransplant HCV-induced liver fibrosis between patients
      treated with CsA or tacrolimus in steroid-containing regimens, whereas CsA in
      steroid-free protocols was associated with reduced severity of fibrosis
      progression at 1 year posttransplant.

PMID- 24456051
TI  - Moderate to severe hidradenitis suppurativa treated with biological therapies.
AB  - Hidradenitis suppurativa is a debilitating disorder that can be difficult to
      manage with current conventional treatment strategies. Given its association with
      proinflammatory cytokines there has been interest in the use of novel biological
      monoclonal antibodies. We describe our experience with the use of these agents in
      six patients in whom conventional treatment had failed, with promising response
      noted in some patients. A growing number of studies now highlight the efficacy of
      these agents. 

PMID- 24456052
TI  - The role of calpains in traumatic brain injury.
AB  - AIM: This article attempts to provide a framework that will help to illustrate
      the roles of calpains in the process of traumatic brain injury (TBI). METHOD:
      This review provides meaningful points about the essential role of calpains in
      the neuropathological changes that follow TBI, identifies useful biomarkers of
      calpain activation and states the important roles of calpain in the treatment of
      TBI. RESULTS: Neuronal calpains can be activated within hours or even minutes
      following contusive or diffuse brain trauma in animals. It has been suggested
      that they are early mediators of neuronal damage. Trauma can produce sustained
      calpain activation. In turn, this may result in axonal degeneration and neuronal
      death in models of TBI. Calpains can cleave cytoskeletal proteins into stable
      proteolytic fragments that have been widely used as biomarkers of the activation
      of calpain. The inhibition of calpains can reduce the functional and behavioural
      deficits by ameliorating axonal pathology and reducing cell deaths in animal
      models of TBI. CONCLUSION: This review concentrates on the current understanding
      of the role of calpains in neuropathology that has been induced by TBI and the
      significance of calpains as a therapeutic target for the treatment of primary and
      secondary injuries that are associated with brain trauma.

PMID- 24456053
TI  - The complementary role of the cerebral hemispheres in recovery from aphasia after
      stroke: a critical review of literature.
AB  - OBJECTIVES: To review the literature on the specific role of the right cerebral
      hemisphere during recovery from aphasia in order to address the lack of consensus
      among authors. To derive a theoretical model reconciling the controversial
      findings in the literature. METHODS: Initial PubMed, MEDLINE (1946 to 5 May 2012)
      and PsycINFO (1806 to first week June 2012) searches on recovery mechanisms from
      aphasia, whether treatment-related or not, retrieved a total of 35 English
      language articles. Articles, cross-referenced in this initial set were also
      reviewed if they met the inclusion criteria, thus resulting in a total of 42
      articles included in this review. MAIN OUTCOMES: Recruitment of the right
      hemisphere during recovery from aphasia can be effective if it occurs during a
      critical time window post-stroke. The recruitment's effectiveness will depend on
      the lesion's location, extent and permanence. Preservation of core language
      processing areas will generate minimal right hemisphere recruitment and vice
      versa. Some experimental studies seem to suggest that the improvement linked to a
      particular hemisphere can be modulated by specific therapy methods. CONCLUSION:
      The specific conditions in which effective right recruitment takes place may have
      important implications for rehabilitation treatment. These findings could lead to
      improved recovery in people suffering from aphasia. However, more research with
      non-invasive brain stimulation is needed.

PMID- 24456054
TI  - Self-concept and self-esteem after acquired brain injury: a control group
      comparison.
AB  - PRIMARY OBJECTIVE: This study examined the multidimensional self-concept, global
      self-esteem and psychological adjustment of individuals with traumatic brain
      injury (TBI) as compared with healthy controls. RESEARCH DESIGN: Group comparison
      on self-report questionnaires. METHODS AND PROCEDURES: Forty-one individuals who
      had sustained a TBI were compared with an age- and gender-matched sample of 41
      trauma-free control participants on the Rosenberg Self Esteem Scale, the
      Tennessee Self Concept Scale (second edition) and the Hospital Anxiety and
      Depression Scales (HADS). MAIN OUTCOMES AND RESULTS: Participants with TBI rated
      significantly lower mean levels of global self-esteem and self-concept on the
      Rosenberg Self Esteem Scale and Tennessee Self Concept Scale than the control
      group. Survivors of TBI rated themselves more poorly on a range of self
      dimensions, including social, family, academic/work and personal self-concept
      compared to controls. They also reported higher mean levels of depression and
      anxiety on the Hospital Anxiety and Depression Scale. Overall self-concept was
      most strongly associated with depressive symptoms and anxiety. CONCLUSIONS: Self
      concept may be lowered following TBI and is associated with negative emotional
      consequences. Clinicians may improve the emotional adjustment of survivors of TBI
      by considering particular dimensions of self-concept for intervention focus.

PMID- 24456055
TI  - Smoking and outcome of traumatic brain injury.
AB  - OBJECTIVE: There is evidence that the cholinergic system is involved in cognitive
      sequels of traumatic brain injury (TBI). Nicotinic acetylcholine receptors
      (nAChRs) are known to have a major role in cognitive functions. Smokers have up
      regulation of these receptors. This study investigated whether smoking is
      associated with the outcome from TBI. METHODS: A specific questionnaire was sent,
      after checking inclusion and exclusion criteria, to 1022 subjects with TBI who
      had visited the neurological outpatient clinic of a university hospital during a
      14-year period. Of these, 689 (67.4%) responded, forming the final study
      population. Associations between demographic variables, injury severity and
      outcome and smoking history were analysed using multivariate methods. RESULTS:
      Smokers were more often men (p < 0.001), younger at the time of the injury (p =
      0.008) and had less education (p < 0.0001). In univariate analysis, non-smokers
      did not differ for outcome of TBI by GOS-E (p = 0.08). Furthermore, in
      multivariate analysis, no association was found between smoking history and TBI
      outcome. CONCLUSIONS: This study does not suggest that smoking affects the
      outcome of TBI.

PMID- 24456056
TI  - Is stroke rehabilitation a metabolic problem?
AB  - BACKGROUND: This study looks at the impact of inflammation during the
      rehabilitation stage of strokes and its effect on neuro-functional recovery.
      METHODS: This study investigated 94 patients suffering from strokes and admitted
      to rehabilitation. Anthropometric characteristics, serum proteins and
      inflammatory markers, plasma amino acids and neurofunction were all assessed.
      RESULTS: 55.3% patients had an inflammatory status (Interleukin-6 = 19.24 +/-
      23.01 pg ml-1 vs. 4.1 +/- 1.6 pg ml-1 for non-inflamed subjects (p < 0.001).
      Inflammation was positively linked to positive proteins (alpha-1 globulin, p <
      0.02) and negatively linked to negative proteins (albumin, p < 0.02; prealbumin,
      p < 0.01; transferrin, p < 0.05) of the acute-phase response. Inflammation was
      associated with low plasma concentrations of total amino acids. For the multiple
      logistic regression analysis, albumin (p < 0.001) and body weight maintenance (p
      < 0.001) were independent predictors of patient functional independence.
      Inflammation in dysphagic stroke (31.9%) patients was associated with more
      accentuated disability compared to non-inflamed dysphagics. The serum positive
      reactant alpha 1 globulin was the most powerful predictor of dysphagia severity
      (p < 0.001). At discharge, dysphagia improvement was associated with improved
      acute-phase negative proteins. CONCLUSIONS: An inflammatory status may persist
      for most patients with strokes during the rehabiliation stage of the disease, its
      prevalence being higher in dysphagic compared to non-dysphagic subjects. The
      improvement in circulating albumin and body weight maintenance are predictors of
      neuro-function, even in dysphagic subjects.

PMID- 24456057
TI  - Virtual reality-based therapy for the treatment of balance deficits in patients
      receiving inpatient rehabilitation for traumatic brain injury.
AB  - OBJECTIVE: To evaluate the feasibility and safety of utilizing a commercially
      available virtual reality gaming system as a treatment intervention for balance
      training. DESIGN: A randomized controlled trial in which assessment and analysis
      were blinded. SETTING: An inpatient rehabilitation facility. INTERVENTION:
      Interventions included balance-based physical therapy using a Nintendo Wii, as
      monitored by a physical therapist, and receipt of one-on-one balance-based
      physical therapy using standard physical therapy modalities available for use in
      the therapy gym. RESULTS: Participants in the standard physical therapy group
      were found to have slightly higher enjoyment at mid-intervention, while those
      receiving the virtual reality-based balance intervention were found to have
      higher enjoyment at study completion. Both groups demonstrated improved static
      and dynamic balance over the course of the study, with no significant differences
      between groups. Correlational analyses suggest a relationship exists between Wii
      balance board game scores and BBS scores for measures taken beyond the baseline
      assessment. CONCLUSIONS: This study provides a modest level of evidence to
      support using commercially available VR gaming systems for the treatment of
      balance deficits in patients with a primary diagnosis of TBI receiving inpatient
      rehabilitation. Additional research of these types of interventions for the
      treatment of balance deficits is warranted.

PMID- 24456058
TI  - Functional independence measure at rehabilitation admission as a predictor of
      return to driving after traumatic brain injury.
AB  - OBJECTIVE: To examine the utility of three common measures as predictors of
      return to driving after traumatic brain injury (TBI): Glasgow Coma Score (GCS)
      within the first 24 hours of injury and both Functional Independence Measure
      (FIM) and Disability Rating Scale (DRS) at rehabilitation admission. METHODS:
      Seventy-two participants with TBI completed a questionnaire that assessed return
      to driving post-TBI, as measured by reinstatement of the driver's license.
      Participants who did not return to driving for non-medical reasons or who had not
      driven pre-injury and did not obtain a driver's license post-injury were excluded
      from analysis. This produced a final sample of 59 participants. Scores on GCS,
      FIM and DRS, leveraged from an existing database, were compared between
      participants who had and those who had not returned to driving post-injury.
      Multiple logistic regression analysis was performed to determine the relationship
      of each predictor variable to return to driving. RESULTS: Only the FIM score at
      rehabilitation admission was significantly associated with return to driving (p <
      0.01). FIM score had a sensitivity of 72% and specificity of 73% with respect to
      return to driving. CONCLUSIONS: This study supports the use of FIM at
      rehabilitation admission as a predictor of return to driving. Future studies
      should be directed at identifying other measures to be used in combination with
      FIM to accurately predict return to driving post-TBI.

PMID- 24456059
TI  - Simvastatin and environmental enrichment effect on recognition and temporal order
      memory after mild-to-moderate traumatic brain injury.
AB  - PRIMARY OBJECTIVE: The purpose of this study was to investigate the effect of
      mild-to- moderate (m-mod) traumatic brain injury (TBI) on spontaneous object (SO)
      recognition and temporal order (TO) memory in male Wistar rats and to compare the
      effects of environmental enrichment (EE) and simvastatin (Sim) on SO and TO
      memory post-injury. RESEARCH DESIGN: A randomized repeated measure experimental
      design was used. METHODS AND PROCEDURE: Seven days after arrival, animals
      received the injury or sham surgery. Using a Y-shaped maze, SO and TO memory was
      assessed in the two groups of animals at 6, 24, 48, 72 hours and 7, 14, 21 and 35
      days post-surgery. Total time exploring each object and discrimination ratio were
      calculated and analysed. Then SO and TO memory were compared between two groups
      that received either Sim or EE for 2 hours daily starting 24 hours post-injury
      and a sham group that received saline for 14 days post-injury. RESULTS: The
      results showed that the injury impaired SO and TO memory compared to the sham up
      to 35 days post-trauma. Injured animals exhibited familiarity preference, novelty
      aversion and impaired TO performance. EE improved the animals' SO recognition
      deficits 7 days post-injury after a shorter delay (1 minute) only and Sim
      reversed TO memory deficits 14 days post-injury after a longer delay (60
      minutes). CONCLUSION: Persistent SO and TO memory deficits follow TBI in animals;
      Simv and EE seem to be promising therapies of TBI memory deficits.

PMID- 24456060
TI  - Baicalin protects PC-12 cells from oxidative stress induced by hydrogen peroxide
      via anti-apoptotic effects.
AB  - PRIMARY OBJECTIVE: To examine the neuroprotection of baicalin, a flavonoid
      compound derived from the dried root of Scutellaria baicalensis Georgi, on
      neurons. RESEARCH DESIGN: A rat PC12 cell line was used to study the
      neuroprotection and possible mechanisms of baicalin on H2O2-induced neuron
      damage. METHODS: Three anti- and one pro-apoptosis genes in PC12 cells were
      examined. Cell apoptosis was induced by H2O2 and apoptotic rate was obtained by
      flow cytometry. MTT for cell viability, immunofluorescence microscopy for
      promoter activity and western blot for gene expression were also employed.
      RESULTS: Data of MTT reduction assay and flow cytometry revealed that viability
      loss and apoptotic rate were reduced by pre-treatment of PC12 cells with baicalin
      for 24 hours. Baicalin was also found to increase SOD, GSH-Px activities and to
      decrease MDA level. Results from Western blot and immunofluorescence microscopy
      showed baicalin increased the expressions of survivin, Bcl-2 and p-STAT3 and
      decreased caspase-3 expression which were attenuated by AG-490. CONCLUSIONS: The
      results point to the possibility of the neuroprotective effects of baicalin on
      neuronal apoptosis induced by oxidative stress and indicate that activation of
      the JAK/STAT signalling pathway might involve the anti-apoptotic effect of
      baicalin.

PMID- 24456061
TI  - Simple tone discriminations are disrupted following experimental frontal
      traumatic brain injury in rats.
AB  - PRIMARY OBJECTIVE: To assess cognitive deficits in a rat model of brain injury.
      RESEARCH DESIGN: Cognitive deficits are some of the most pervasive and enduring
      symptoms of frontal traumatic brain injury (TBI) in human patients. In animal
      models, the assessment of cognitive deficits from TBI has primarily been limited
      to tests of spatial learning. Recently, simple discrimination performance has
      been shown to be sensitive to frontal brain damage. The current study provides a
      detailed characterization of deficits in a two-choice tone discrimination
      following a bilateral frontal controlled cortical impact injury. METHODS AND
      PROCEDURES: Rats were trained on a two-tone discrimination task in a standard
      operant chamber, then either a frontal brain injury was delivered or sham
      procedures performed. Following recovery, they were re-tested on the
      discrimination task and then tested on a reversal of the discrimination. MAIN
      OUTCOMES AND RESULTS: Frontal injury caused substantial deficits in responding
      and discrimination accuracy as well as an increase in side bias. CONCLUSIONS:
      Based on the outcomes seen in this study, discrimination and other operant tasks
      may provide a sensitive tool to assess the effect of therapeutic agents on
      cognitive deficits in animal models, which could lead to improved
      characterization of deficits and yield an improved assessment tool to aid in drug
      discovery.

PMID- 24456062
TI  - Preliminary efficacy of an attention and memory intervention post-childhood brain
      injury.
AB  - OBJECTIVE: Impairments in attention and memory are common consequences following
      paediatric acquired brain injury (ABI). Despite this, there is a scarcity of
      evidence-based interventions for these difficulties. The current study aimed to
      pilot the feasibility and efficacy of the English version of the Amsterdam Memory
      and Attention Test for Children (Amat-c) and to identify ecologically valid
      measures sensitive to post-evaluation improvements. It was expected that children
      with attention and memory difficulties post-TBI would show improved performance
      post-intervention on traditional cognitive measures and on measures of everyday
      performance. METHODS AND PROCEDURES: Three children (case study design) with an
      acquired brain injury (near drowning, birth delivery complications, fall from a
      horse) and currently between the ages of 8-13 were identified through audits of
      presentations to a metropolitan paediatric hospital. Each child underwent
      screening, pre-intervention and post-intervention assessments (immediate and 6
      months). OUTCOMES/RESULTS: Results indicated improved performance in the areas of
      attention and memory from pre- to post-intervention, with gains maintained at 6
      months post-intervention. CONCLUSIONS AND IMPLICATIONS: Findings demonstrate
      initial support for efficacy of the Amat-c and its use with survivors of child
      ABI to alleviate common cognitive and functional consequences. A larger study is
      needed to further confirm these findings.

PMID- 24456063
TI  - Organic dyes containing carbazole as donor and pi-linker: optical,
      electrochemical, and photovoltaic properties.
AB  - A series of new metal free organic dyes containing carbazole as donor and pi
      linker have been synthesized and characterized as effective sensitizers for dye
      sensitized solar cells (DSSCs). The carbazole functionalized at C-2 and C-7
      served as electron-rich bridge. The donor property of the carbazole is
      substantially enhanced on introduction of tert-butyl groups at C-3 and C-6
      positions and the oxidation propensity of the dyes increased on insertion of
      thiophene unit in the conjugation pathway. These structural modifications fine
      tuned the optical and electrochemical properties of the dyes. Additionally, the
      presence of tert-butyl groups on the carbazole nucleus minimized the
      intermolecular interactions which benefited the performance of DSSCs. The dyes
      served as efficient sensitizers in DSSCs owing to their promising optical and
      electrochemical properties. The efficiency of DSSCs utilizing these dyes as
      sensitizers ranged from 4.22 to 6.04%. The tert-butyl groups were found to
      suppress the recombination of injected electrons which contributed to the
      increment in the photocurrent generation (JSC) and open circuit voltage (VOC). A
      dye with carbazole donor functionalized with tert-butyl groups and the
      conjugation bridge composed of 2,7-disubstituted carbazole and thiophene
      fragments exhibited higher VOC value. However, the best device efficiency was
      observed for a dye with unsubstituted carbazole donor and the pi-linker featuring
      carbazole and bithiophene units due to the high photocurrent generation arising
      from the facile injection of photogenerated electrons into the conduction band of
      titanium dioxide (TiO2) facilitated by the low-lying LUMO. 

PMID- 24456064
TI  - Isolation and structures of pipecolidepsins A and B, cytotoxic cyclic
      depsipeptides from the Madagascan sponge Homophymia lamellosa.
AB  - Two new cyclic depsipeptides, pipecolidepsins A and B (1 and 2), have been
      isolated from the sponge Homophymia lamellosa collected off the coast of
      Madagascar. Their structures were determined by a combination of NMR experiments
      and by LC-MS analysis of the amino acid fragments obtained by hydrolysis and
      derivatization using Marfey's reagent. In addition to several common amino acids,
      these peptides contain unusual residues, including 2-amino-3-hydroxy-4,5
      dimethylhexanoic acid, 3-ethoxyasparagine, 3,4-dimethylglutamine, 4,7-diamino-2,3
      dihydroxy-7-oxoheptanoic acid, and 3-hydroxyaspartic acid as well as a terminal 3
      hydroxy-2,4,6-trimethylheptanoic acid residue. Pipecolidepsins A and B displayed
      cytotoxic activity against a panel of different human tumor cell lines. 

PMID- 24456065
TI  - A randomized, double-blind, placebo-controlled, parallel-group study to evaluate
      the efficacy and safety of osmotic-controlled release oral delivery system
      methylphenidate HCl in adults with attention-deficit/hyperactivity disorder in
      Japan.
AB  - OBJECTIVES: To evaluate the safety and efficacy of osmotic-controlled release
      oral delivery system (OROS) methylphenidate (MPH) HCl in adults with attention
      deficit/hyperactivity disorder (ADHD). METHODS: In this study, 284 adults with
      ADHD were randomized to OROS MPH or placebo. During the 4-week titration period,
      patients were titrated from a starting dose of 18 mg once daily to an
      individually-optimized dose of up to 72 mg once daily in weekly 18-mg increments.
      Patients continued on their individualized dose during the 4-week efficacy
      assessment period. The primary efficacy endpoint was change in DSM-IV Total ADHD
      Symptoms subscale score of Conners' Adult ADHD Rating Scale-Observer: Screening
      Version (CAARS-O:SV) from baseline to endpoint. RESULTS: The mean change in DSM
      IV Total ADHD Symptoms subscale score of CAARS-O:SV was significantly larger with
      OROS MPH compared with placebo (P < 0.0001, ANCOVA). Similar results were
      observed for the majority of secondary endpoints, including CAARS-O:SV total
      score and other subscale scores. Although treatment-emergent adverse events were
      reported more frequently in the OROS MPH group (81.8%) versus the placebo group
      (53.9%), OROS-MPH showed a well-tolerated safety profile overall. CONCLUSIONS:
      OROS MPH in a dose range of 18-72 mg once daily was effective and well-tolerated
      in adult patients with ADHD.

PMID- 24456066
TI  - Molecular analysis of immunized Jr(a-) or Lan- patients and validation of a high
      throughput genotyping assay to screen blood donors for Jr(a-) and Lan-
      phenotypes.
AB  - BACKGROUND: Individuals with anti-Jr(a) or anti-Lan are ideally transfused with
      rare Jr(a-) or Lan- red blood cells. We characterized mutations in Dutch Jr(a-)
      and Lan- individuals and developed a high-throughput genotyping assay to detect
      Jr(a-) and Lan- donors. STUDY DESIGN AND METHODS: Six Jr(a-) and seven Lan-
      persons, who all made anti-Jr(a) or anti-Lan, were sequenced for ABCG2 or ABCB6
      and the copy number of ABCG2 and ABCB6 was determined. A total of 3366 Caucasian,
      621 black, and 333 Chinese donors were screened with a high-throughput screening
      assay targeting frequently occurring mutations causing the Jr(a-) or Lan-
      phenotype. RESULTS: In the six tested Jr(a-) individuals previously described,
      c.376C > T, c.706C > T, and c.736C > T nonsense mutations in ABCG2 were detected.
      In the seven Lan- individuals 12 different mutations, of which 10 underlie the
      Lan- phenotype, were detected. No copy number variation was detected for ABCG2
      and ABCB6. The high-throughput screening assay detected five Caucasian donors
      heterozygous for the c.706C > T or 736C > T mutation in ABCG2 and nine Caucasian
      donors heterozygous for the 574C > T mutation in ABCB6. No black or Chinese
      donors were found positive for a mutation. CONCLUSION: We describe eight new
      mutations in ABCB6 of which seven, including three missense mutations, underlie
      the Lan- phenotype and determine that a complete gene deletion of ABCG2 or ABCB6
      is not responsible for the Jr(a-) or Lan- phenotype, respectively. The extended
      heterogeneity of mutations causing the Jr(a-) or Lan- phenotype in most
      populations makes genetic screening for the Jr(a-) and Lan- phenotype inefficient
      in those populations.

PMID- 24456067
TI  - Association between restriction of activity related to chronic diseases and
      suicidal ideation in older adults in Korea.
AB  - AIM: The aim of the present study was to show an association between restricted
      activity related to chronic diseases and suicidal ideation (SI) in elderly Korean
      adults after adjusting for age, sex, mental health status, socioeconomic position
      and health behavior factors. METHODS: The study sample included 3545 Korean men
      (n=1473) and women (n=2073), aged over 65 years from the 2007-2009 Korea National
      Health and Nutrition Examination Survey carried out by the Ministry of Health and
      Welfare of Korea. Participants were classified into two groups based on whether
      they had previously experienced suicidal thoughts. Restricted activity was
      related to chronic conditions, such as cardiovascular diseases, cerebrovascular
      accident and so on. We analyzed the data using Student's t-test or chi(2) -test.
      Multiple logistic regression analysis was used to determine the association
      between restricted activity as the independent variable and SI as the dependent
      variable after adjustment for confounders. RESULTS: The proportion of
      participants with SI population was 29.1%. People with SI reported a
      significantly higher proportion of restrictive activity (62.3%) than those who
      did not have SI (34.5%). The adjusted risk excess (OR) of SI was statistically
      significant with regard to restricted activity (2.11, 95% CI 1.65-2.70; 2.85, 95%
      CI 1.95-4.15) in males; 1.69 (95% CI 1.22-2.34) in females after adjustment for
      potential confounders. In particular, women who lived alone showed high adjusted
      OR (1.50, 95% CI 1.01-2.24). CONCLUSIONS: Statistical analyses from this
      community-based, random sample drawn from a selected sample of the elderly Korean
      population showed that restricted activity appears to be significantly associated
      with SI.

PMID- 24456068
TI  - Dynamic vibration cooperates with connective tissue growth factor to modulate
      stem cell behaviors.
AB  - Vocal fold disorders affect 3-9% of the U.S. population. Tissue engineering
      offers an alternative strategy for vocal fold repair. Successful engineering of
      vocal fold tissues requires a strategic combination of therapeutic cells,
      biomimetic scaffolds, and physiologically relevant mechanical and biochemical
      factors. Specifically, we aim to create a vocal fold-like microenvironment to
      coax stem cells to adopt the phenotype of vocal fold fibroblasts (VFFs). Herein,
      high frequency vibratory stimulations and soluble connective tissue growth factor
      (CTGF) were sequentially introduced to mesenchymal stem cells (MSCs) cultured on
      a poly(E-caprolactone) (PCL)-derived microfibrous scaffold for a total of 6 days.
      The initial 3-day vibratory culture resulted in an increased production of
      hyaluronic acids (HA), tenascin-C (TNC), decorin (DCN), and matrix
      metalloproteinase-1 (MMP1). The subsequent 3-day CTGF treatment further enhanced
      the cellular production of TNC and DCN, whereas CTGF treatment alone without the
      vibratory preconditioning significantly promoted the synthesis of collagen I (Col
      1) and sulfated glycosaminoglycans (sGAGs). The highest level of MMP1, TNC, Col
      III, and DCN production was found for cells being exposed to the combined
      vibration and CTGF treatment. Noteworthy, the vibration and CTGF elicited a
      differential stimulatory effect on elastin (ELN), HA synthase 1 (HAS1), and
      fibroblast-specific protein-1 (FSP-1). The mitogenic activity of CTGF was only
      elicited in naive cells without the vibratory preconditioning. The combined
      treatment had profound, but opposite effects on mitogen-activated protein kinase
      (MAPK) pathways, Erk1/2 and p38, and the Erk1/2 pathway was critical for the
      observed mechano-biochemical responses. Collectively, vibratory stresses and CTGF
      signals cooperatively coaxed MSCs toward a VFF-like phenotype and accelerated the
      synthesis and remodeling of vocal fold matrices. 

PMID- 24456069
TI  - A 3-D artificial colon tissue mimic for the evaluation of nanoparticle-based drug
      delivery system.
AB  - Functional engineered nanoparticles are promising drug delivery carriers. As the
      construction of a functional nanocarrier always needs the optimization of
      multiple technical variables, efficient in vitro high-throughput evaluation
      methods would help to shorten the development cycle. In the present study, we
      generated a tissue mimic of the colon of inflammatory bowel disease (IBD)
      patients. Generally, Caco-2 cells and THP-1 cells were grown in a 3-D matrix with
      different number, spatial distribution and specific extracellular cell matrix
      (ECM) composition according to real healthy and inflamed animal colon tissues.
      After interlerukin-1beta/lipopolysaccharide (LPS) stimulation, the artificial
      model closely resembled the pathological features of IBD patient's colon,
      including massive cytokines and mucus production, epithelium defect and
      leukocytic infiltration. The tissue and cellular uptake of three different
      nanoparticles in the artificial model was similar to that in 2,4,6
      trinitrobenzenesulfonic acid (TNBS) colitic mice. Most importantly, our
      artificial tissue can be placed into 96-well plates for high-throughput screening
      of drug delivery carriers for the treatment of IBD. Our study suggested a readily
      achievable way to improve current methodologies for the development of colon
      targeted drug delivery systems. 

PMID- 24456070
TI  - Single-molecule analysis of Pseudomonas fluorescens footprints.
AB  - Understanding the molecular mechanisms of bacterial adhesion and biofilm
      formation is an important topic in current microbiology and a key in nanomedicine
      for developing new antibacterial strategies. There is growing evidence that the
      production of extracellular polymeric substances at the cell-substrate interface
      plays a key role in strengthening bacterial adhesion. Yet, because these adhesive
      polymers are available in small amounts and are localized at interfaces, they are
      difficult to study using traditional techniques. Here, we use single-molecule
      atomic force microscopy (AFM) to functionally analyze the biophysical properties
      (distribution, adhesion, and extension) of bacterial footprints, that is,
      adhesive macromolecules left on substrate surfaces after removal of the attached
      cells. We focus on the large adhesin protein LapA from Pseudomonas fluorescens,
      which mediates cell attachment to a wide diversity of surfaces. Using AFM tips
      functionalized with specific antibodies, we demonstrate that adhesion of bacteria
      to hydrophobic substrates leads to the active accumulation of the LapA protein at
      the cell-substrate interface. We show that single LapA proteins left on the
      substrate after cell detachment localize into microscale domains corresponding to
      the bacterial size and exhibit multiple adhesion peaks reflecting the adhesion
      and extension of adsorbed LapA proteins. The mechanical behavior of LapA-based
      footprints makes them ideally suited to function as multipurpose bridging
      polymers, enabling P. fluorescens to attach to various surfaces. Our experiments
      show that single-molecule AFM offers promising prospects for characterizing the
      biophysics and dynamics of the cell-substrate interface in the context of
      bacterial adhesion, on a scale that was not accessible before. 

PMID- 24456071
TI  - Resveratrol oligomers inhibit biofilm formation of Escherichia coli O157:H7 and
      Pseudomonas aeruginosa.
AB  - Biofilm formation is closely related to bacterial infection and is also a
      mechanism of antimicrobial resistance. Hence, the antibiofilm approach provides
      an alternative to an antibiotic strategy. In this study, the antibiofilm
      activities of resveratrol (1) and five of its oligomers, namely, epsilon
      viniferin (2), suffruticosol A (3), suffruticosol B (4), vitisin A (5), and
      vitisin B (6), were investigated against enterohemorrhagic Escherichia coli
      O157:H7 and Pseudomonas aeruginosa PA14. Vitisin B (6), a stilbenoid tetramer,
      was found to inhibit biofilm formation by the two bacteria the most effectively
      and at 5 MUg/mL inhibited E. coli O157:H7 biofilm formation by more than 90%. 

PMID- 24456072
TI  - Granulocyte concentrates from a single high-yield apheresis can be split to
      support multiple patients.
AB  - Allogeneic granulocyte transfusion has evolved into a viable therapeutic option
      for immunocompromised severely neutropenic leukemic patients and those with
      hematopoietic stem cell transplant with life-threatening bacterial and fungal
      infections. The collection of larger cell doses of granulocyte concentrates (GCs)
      has been facilitated by the stimulation of donors with granulocyte colony
      stimulating factor (G-CSF) and dexamethasone. The synergistic effect of G-CSF and
      dexamethasone has allowed the collection of larger cell doses of GCs and its use
      has increased steadily. This has allowed us to split the high-yield GC products
      and facilitated distribution of the split GC products to a second or third
      patient who needs GCs but lacks donors. The main objective of this article was to
      present our rationale for splitting GC products and how the split GC units were
      transfused to multiple patients. We believe that split GCs are as equally
      effective as unsplit GCs and that multiple patients benefit from splitting GCs.

PMID- 24456073
TI  - A novel Isospora species (Apicomplexa: Eimeriidae) from warblers (Passeriformes:
      Parulidae) of Costa Rica.
AB  - Five of 16 (31%) rufous-capped warblers (Basileuterus rufifrons) and 2 of 5 (40%)
      ovenbirds ( Seiurus aurocapilla ) sampled from Costa Rica were positive for a
      novel species of Isospora. Oocysts have a thin, smooth, double-layered, colorless
      wall and measure 22.3 MUm +/- 1.6 MUm * 24.3 MUm +/- 1.5 MUm (19-25 MUm * 21-28
      MUm) with an average length-width (L/W) ratio of 1.0 (1-1.3). Oocyst residuum and
      micropyle are absent, but 0-4 spherical to cigar-shaped polar granules (1-2.5
      MUm) are present. Sporocysts are ovoid and measure 11.8 MUm +/- 0.9 MUm * 16 MUm
      +/- 1.7 MUm (10-14 MUm * 12-19 MUm) with an average L/W ratio of 1.6 (1.0-1.9). A
      knob-like Stieda body continuous with the sporocyst wall and a trapezoidal
      compartmentalized substieda body are present. Each sporocyst contained 4
      sporozoites and a diffuse sporocyst residuum consisting of many variable-sized
      granules, some as large as 2 MUm. This is the second description of an Isospora
      species in New World warblers (Passeriformes: Parulidae) and the first report of
      Isospora from both the rufous-capped warbler and ovenbird.

PMID- 24456074
TI  - Human catalase gene polymorphism (CAT C-262T) and risk of male infertility.
AB  - Infertility is the failure of a couple to engender after endeavouring at least
      one full year of unprotected intercourse. It has been reported that reactive
      oxygen species contributed to pathogenesis of various disease. To inactivate ROS
      cells biosynthesise several antioxidant enzymes, one of them is catalase which
      contributes H2 O2 to H2 O and O2 . This study set out to delineate the
      association of catalase C-262T polymorphism with idiopathic male infertility. The
      study included 195 men with idiopathic infertility and 190 healthy volunteers.
      Genomic DNA was extracted from peripheral blood leucocytes. Genotype and allele
      frequencies were determined in patients and controls using allele-specific PCR
      (AS-PCR). The prevalence of genotype frequencies of the CAT CC/CT/TT was 31.79%,
      65.12% and 3.07%, respectively, in infertile subjects, as against 24.73%, 55.26%
      and 20%, respectively, in healthy volunteers. Statistical analysis has emerged
      significant difference from the comparison of either genotype (P < 0.05). Taking
      into accounts of results, the catalase C-262T polymorphism indicates that CAT
      262T/T genotype confers less susceptibility to male infertility. Further studies
      with larger numbers of patients are required for further evaluation and
      confirmation of our finding.

PMID- 24456075
TI  - A novel model enhances HbA1c-based diabetes screening using simple
      anthropometric, anamnestic, and demographic information.
AB  - BACKGROUND: The sensitivity of HbA1c is not optimal for the screening of patients
      with latent diabetes. We hypothesize that simple healthcare information could
      improve accuracy. METHODS: We retrospectively analyzed data, including HbA1c,
      from multiple years from the National Health and Nutrition Examination Survey
      (NHANES) database (2005-2010). The data were used to create a logistic regression
      classification model for screening purposes. RESULTS: The study evaluated data
      for 5381 participants, including 404 with undiagnosed diabetes. The HbA1c
      screening data were supplemented with information about age, waist circumference,
      and physical activity in the HbA1c+ model. Alone, HbA1c alone had a receiver
      operating characteristics (ROC) curve for the area under the curve (AUC) of 0.808
      (95% confidence interval [CI] 0.792-0.834). The HbA1c+ model had an ROC AUC of
      0.851 (95% CI 0.843-0.872). There was a significant difference in the AUC between
      our model and using HbA1c without supplementary information (P < 0.05).
      CONCLUSIONS: We have developed a novel screening model that could help improve
      screening for type 2 diabetes with HbA1c. It seems beneficial to systematically
      add additional patient healthcare information in the process of screening with
      HbA1c.

PMID- 24456076
TI  - Bioenergetic modulation overcomes glucocorticoid resistance in T-lineage acute
      lymphoblastic leukaemia.
AB  - Drug-resistant forms of acute lymphoblastic leukaemia (ALL) are a leading cause
      of death from disease in children. Up to 25% of patients with T-cell ALL (T-ALL)
      develop resistance to chemotherapeutic agents, particularly to glucocorticoids
      (GCs), a class of drug to which resistance is one of the strongest indicators of
      poor clinical outcome. Despite their clinical importance, the molecular
      mechanisms that underpin GC resistance and leukaemia relapse are not well
      understood. Recently, we demonstrated that GC-resistance is associated with a
      proliferative metabolism involving the up-regulation of glycolysis, oxidative
      phosphorylation and cholesterol biosynthesis. Here we confirm that resistance is
      directly associated with a glycolytic phenotype and show that GC-resistant T-ALL
      cells are able to shift between glucose bioenergetic pathways. We evaluated the
      potential for targeting these pathways in vitro using a glycolysis inhibitor, 2
      deoxyglucose (2DG), and the oxidative phosphorylation inhibitor oligomycin in
      combination with methylprednisolone (MPRED). We found that oligomycin synergized
      with MPRED to sensitize cells otherwise resistant to GCs. Similarly we observed
      synergy between MPRED and simvastatin, an inhibitor of cholesterol metabolism.
      Collectively, our findings suggest that dual targeting of bioenergetic pathways
      in combination with GCs may offer a promising therapeutic strategy to overcome
      drug resistance in ALL. 

PMID- 24456077
TI  - Potency prediction of beta-secretase (BACE-1) inhibitors using density functional
      methods.
AB  - Scoring potency is a main challenge for structure based drug design. Inductive
      effects of subtle variations in the ligand are not possible to accurately predict
      by classical computational chemistry methods. In this study, the problem of
      predicting potency of ligands with electronic variations participating in key
      interactions with the protein was addressed. The potency was predicted for a
      large set of cyclic amidine and guanidine cores extracted from beta-secretase
      (BACE-1) inhibitors. All cores were of similar size and had equal interaction
      motifs but were diverse with respect to electronic substitutions. A density
      functional theory approach, in combination with a representation of the active
      site of a protein using only key residues, was shown to be predictive. This
      computational approach was used to guide and support drug design, within the time
      frame of a normal drug discovery design cycle. 

PMID- 24456078
TI  - Anti-IL-36R antibodies, potentially useful for the treatment of psoriasis: a
      patent evaluation of WO2013074569.
AB  - The IL-36 family of cytokines and receptors seems to play a role in the
      pathogenesis of both pustular psoriasis, and the much more common variant, plaque
      type psoriasis. Human skin biopsies from patients with psoriasis show
      overexpression of IL-36 and mice that lack the inhibitory IL-36 receptor (IL
      36Ra) antagonist develop psoriasis, suggesting that signaling through the IL-36R
      may drive the skin lesions of psoriasis. Currently, no drugs targeting IL-36 are
      used in the treatment of psoriasis. The patent WO2013074569 describes an antibody
      to the IL-36R that is proposed as a potential therapy for psoriasis. 

PMID- 24456079
TI  - Toll-like receptor agonists: a patent review (2011 - 2013).
AB  - INTRODUCTION: Toll-like receptors (TLRs) are a crucial part of the innate
      immunity and present the first line of defense against pathogens. In humans,
      there are ten TLRs, with TLR3, 7, 8 and 9 located in intracellular vesicles and
      the remaining expressed on the cell surface. These transmembrane protein
      receptors recognize a wide range of pathogen components. A large number of TLR
      agonists, either derived from pathogen components or modified synthetic
      molecules, were developed and investigated for their ability to stimulate an
      immune response. AREAS COVERED: This review includes an updated summary (2011 -
      2013) of TLR agonists that have been published in patent applications and/or
      progressed to clinical studies, with an emphasis on their chemical structure,
      immune response, prophylactic and therapeutic outcomes. EXPERT OPINION: A number
      of factors have contributed to the design and development of TLR agonists such as
      solving the crystal structures of TLR bound to their ligands, improvements in our
      understanding of the signaling pathway activated after TLR stimulation and the
      identification of the native ligands of all human TLRs. Some of the TLR agonists
      have been approved for human use by the FDA while others have reached clinical
      studies in Phases I, II and III. Generally, immunotherapy based on TLR agonists
      is very promising for the prevention and/or treatment of several disorders
      including cancer, allergy and microbial infections. However, many TLR agonists
      were withdrawn from further studies as they either lacked efficacy or caused
      serious side effects.

PMID- 24456080
TI  - Retinoid X receptor ligands: a patent review (2007 - 2013).
AB  - INTRODUCTION: Retinoid X receptors (RXRs) are nuclear receptors that act as
      ligand-dependent transcription factors. RXRs function as homodimers or as
      heterodimers with other nuclear receptors, such as retinoic acid receptors,
      PPARs, liver X receptors, farnesoid X receptor, vitamin D receptor or thyroid
      hormone receptors. RXR ligands (agonists or antagonists) show various
      physiological effects, depending on their partner receptors. RXR agonist
      bexarotene (Targretin(r)) is used for the treatment of cutaneous T-cell lymphoma
      in clinical practice. RXR agonists were also reported to be useful for treatment
      of type 2 diabetes, autoimmune disease and Alzheimer's disease. RXR antagonists
      were also reported to be effective in type 2 diabetes treatment. AREAS COVERED:
      Here patent applications (2007 - 2013) concerning RXR ligands are summarized, and
      the usefulness of RXR ligands as pharmaceutical agents is discussed. EXPERT
      OPINION: RXR agonists show a wide variety of biological effects. However, they
      cause serious side effects, such as blood triglyceride elevation, hypothyroidism
      and others. Thus, for clinical application of RXR agonists, abrogation of these
      side effects is required. RXR heterodimer-selective agonists and RXR partial
      agonists exhibiting desired effects without side effects are expected to find
      clinical application.

PMID- 24456081
TI  - Boron-containing compounds: chemico-biological properties and expanding medicinal
      potential in prevention, diagnosis and therapy.
AB  - INTRODUCTION: Although the medicinal use of boron-containing compounds (BCCs) had
      long been limited to antiseptics, in the last few decades, these compounds have
      been used as antibiotics or chemotherapeutic agents. In the last few years, boron
      has been included in the moieties of many known drugs to improve their capacity
      in binding to their respective target receptors. AREAS COVERED: The current
      review focuses on research and patent literature of the last decade related to
      the development of BCCs as preventive, diagnostic and therapeutic tools. It
      explores the possible mechanisms of action of these compounds as well as the
      advantageous features of their structure and chemico-pharmacological properties.
      EXPERT OPINION: Although uncertainties exist about the mechanism of action of
      BCCs, increasing evidence about their toxicological profile strongly suggests
      that many can be safely administered to humans. Even stronger evidence exists
      regarding the capacity of BCCs to reach multiple targets that are involved in the
      treatment of common diseases. It seems fair to say that some BCCs will reach the
      market for medicinal use in the near future, not only for targeting microbial or
      neoplastic systems but also for acting on cell-signaling processes involved in
      many other disorders.

PMID- 24456082
TI  - Use of umbilical cord and cord blood-derived stem cells for tissue repair and
      regeneration.
AB  - INTRODUCTION: Potential use of umbilical cord (UC) is one of the most exciting
      frontiers in medicine for repairing damaged tissues. UC and cord blood-derived
      stem cells are the world's largest potential sources of stem cells. UC contains a
      mixture of stem and progenitor cells at different lineage commitment stages and
      UC has been verified as a candidate for cell-based therapies and tissue
      engineering applications due to the capability of these cells for extensive self
      renewal and multi-lineage character in differentiation potential. AREAS COVERED:
      UC-based repair or regeneration of organs (i.e., heart, nerve, skin, etc.) is a
      high-priority research worldwide. EXPERT OPINION: The aim of this review is to
      summarize the knowledge about UC with main focus on its applications for tissue
      repair and regeneration.

PMID- 24456083
TI  - Ammonia capture in porous organic polymers densely functionalized with Bronsted
      acid groups.
AB  - The elimination of specific environmental and industrial contaminants, which are
      hazardous at only part per million to part per billion concentrations, poses a
      significant technological challenge. Adsorptive materials designed for such
      processes must be engendered with an exceptionally high enthalpy of adsorption
      for the analyte of interest. Rather than relying on a single strong interaction,
      the use of multiple chemical interactions is an emerging strategy for achieving
      this requisite physical parameter. Herein, we describe an efficient, catalytic
      synthesis of diamondoid porous organic polymers densely functionalized with
      carboxylic acids. Physical parameters such as pore size distribution, application
      of these materials to low-pressure ammonia adsorption, and comparison with
      analogous materials featuring functional groups of varying acidity are presented.
      In particular, BPP-5, which features a multiply interpenetrated structure
      dominated by <6 A pores, is shown to exhibit an uptake of 17.7 mmol/g at 1 bar,
      the highest capacity yet demonstrated for a readily recyclable material. A
      complementary framework, BPP-7, features slightly larger pore sizes, and the
      resulting improvement in uptake kinetics allows for efficient adsorption at low
      pressure (3.15 mmol/g at 480 ppm). Overall, the data strongly suggest that the
      spatial arrangement of acidic sites allows for cooperative behavior, which leads
      to enhanced NH3 adsorption. 

PMID- 24456084
TI  - A survey of epidermolysis bullosa care in the United States and Canada.
AB  - Epidermolysis bullosa (EB) is a group of rare, inherited, blistering diseases
      that typically present in infancy. EB is not curable, and treatment is entirely
      supportive. There is a paucity of standardized recommendations to guide
      management. To assess the current state of EB care, an original online survey was
      conducted targeting attending physicians experienced with the care of EB. Members
      of the Society for Pediatric Dermatology residing in the United States and Canada
      served as the source pool. Parameters assessed included clinic visits,
      availability of subspecialists, and performance of surveillance studies. Fifty
      six completed surveys were analyzed. Most providers saw between 1 and 10
      individuals with EB per year in a general dermatology clinic. For each EB type
      there was considerable variation in the frequency of clinic visits, availability
      and use of specialists, and use of laboratory and imaging studies. Some agreement
      was observed in the frequency of follow-up for infants with more severe EB types,
      as well as for the components of a history, physical, and routine laboratory
      studies. These findings describe variations in the current state of EB care that
      pediatric dermatologists provide. The development and acceptance of evidence
      based guidelines and outcome measures may lead to greater uniformity in EB care. 

PMID- 24456085
TI  - Coping in adult patients with severe haemophilia.
AB  - An adequate use of coping strategies could help patients to deal with disease
      related stress. The study aim was to explore coping behaviour in adult patients
      with severe haemophilia and its possible determinants. Coping was assessed
      through three basic dimensions (task-oriented, emotion-oriented and avoidance
      coping), using the short version of the Coping Inventory for Stressful Situations
      (CISS-21). Patients' scores were compared with Dutch working men (N = 374),
      according to three categories: low use (<P25 of normal), average use (P25-P75)
      and high use (>P75). Determinants were measured using questionnaires on
      activities (Haemophilia Activities List), participation (Impact on Participation
      and Autonomy Questionnaire), physical functioning [physical component of the
      Dutch Arthritis Impact Measurement Scales-2 (D-AIMS2)] and socio-psychological
      health (psychological component of the D-AIMS2). In total, 86 adults with severe
      haemophilia (FVIII/IX<1%) were included. The median age was 38 years (range: 18
      68) with 85% affected with haemophilia A and 75% using prophylaxis. Patients with
      haemophilia used task-oriented coping as frequently as the control group (P =
      0.13); but used significantly less emotion-oriented coping (57% vs. 25%, P <
      0.05) and avoidance coping (P < 0.05). Emotion-oriented coping showed a strong
      correlation with socio-psychological health (r = 0.67) and weak correlations with
      participation (r = 0.32) and social interaction (r = 0.29). Other associations of
      coping strategies with patient characteristics of health status could not be
      demonstrated. Overall, patients predominantly used the task-oriented approach to
      deal with their disease; the use of this strategy was comparable to the control
      group. Having a poor psychological health, less social interaction and/or less
      participation in daily life was associated with an increased use of emotion
      oriented coping. 

PMID- 24456086
TI  - RNA-Seq transcriptome analysis of Spirodela dormancy without reproduction.
AB  - BACKGROUND: Higher plants exhibit a remarkable phenotypic plasticity to adapt to
      adverse environmental changes. The Greater Duckweed Spirodela, as an aquatic
      plant, presents exceptional tolerance to cold winters through its dormant
      structure of turions in place of seeds. Abundant starch in turions permits them
      to sink and escape the freezing surface of waters. Due to their clonal
      propagation, they are the fastest growing biomass on earth, providing yet an
      untapped source for industrial applications. RESULTS: We used next generation
      sequencing technology to examine the transcriptome of turion development
      triggered by exogenous ABA. A total of 208 genes showed more than a 4-fold
      increase compared with 154 down-regulated genes in developing turions. The
      analysis of up-regulated differential expressed genes in response to dormancy
      exposed an enriched interplay among various pathways: signal transduction, seed
      dehydration, carbohydrate and secondary metabolism, and senescence. On the other
      side, the genes responsible for rapid growth and biomass accumulation through DNA
      assembly, protein synthesis and carbon fixation are repressed. Noticeably, three
      members of late embryogenesis abundant protein family are exclusively expressed
      during turion formation. High expression level of key genes in starch synthesis
      are APS1, APL3 and GBSSI, which could artificially be reduced for re-directing
      carbon flow from photosynthesis to create a higher energy biomass. CONCLUSIONS:
      The identification and functional annotation of differentially expressed genes
      open a major step towards understanding the molecular network underlying
      vegetative frond dormancy. Moreover, genes have been identified that could be
      engineered in duckweeds for practical applications easing agricultural production
      of food crops.

PMID- 24456087
TI  - Parkinson Activity Scale: cross-cultural adaptation and reliability of the
      Brazilian version.
AB  - AIM: Following the substantial growth of the elderly population in Brazil, there
      has been an increase in cases of Parkinson's disease (PD), which raises the need
      for reliable and culturally adapted scales specific to the disease. The Parkinson
      Activity Scale (PAS) was developed in order to assess the activity level of
      people with PD through tasks related to mobility. The aims of the present study
      were to translate the cross-cultural adaptation of the PAS into Brazilian
      Portuguese and analyze its reliability during the "on" phase of PD. METHODS: A
      total of 25 patients with PD participated in the study. The intrarater
      reliability was evaluated using a test-retest design with a 1-week interval.
      RESULTS: The interrater reliability was tested twice on the same day by two
      different raters. The intraclass correlation coefficient (ICC), and the Bland and
      Altman plots were calculated to examine the test-retest and interrater
      reliabilities for total score of the PAS, whereas the weighted Kappa (Wk) was
      used to assess interrater agreement. The interrater ICC was 0.89 and Wk was 0.65
      for the total score. For intrarater reliability, the total score ICC was 0.88.
      CONCLUSIONS: The present study suggests that the Brazilian version of the PAS is
      a reliable instrument for the assessment of mobility in elderly patients with PD.

PMID- 24456089
TI  - The effect of color on the production of responses to Rorschach cards VIII, IX,
      and X in age groups of 11-12 and 15-16 years.
AB  - The effect of color on the production of responses to the Rorschach task has been
      considered by investigators from 2 different positions: (a) that color has little
      effect on the production of responses, and (b) that color increases the number of
      responses. Some previous results found by the current investigators have
      supported the first position for the last 3 fully colored Rorschach cards (VIII,
      IX, and X), in children from 5 to 12 years old. Other studies of ours, however,
      have confirmed the second position for these same cards with a group of young
      adults 17 to 23 years old. As there was no increase of responses up to age 12,
      for this study we hypothesized a developmental effect in adolescence such that
      there would be an increase in the production of responses to the colored
      Rorschach cards at the age of 15 to 16 years, and this is what the results
      indicate. From a pragmatic standpoint, these results imply a revision of
      interpretive meaning for the Color and Affective Ratio variables in children's
      protocols. Our results also indicate that color cannot be regarded as a means of
      expression of affect at age 11 to 12 like it will be from age 15 to 16 and on.

PMID- 24456088
TI  - Pineal gland volume in primary insomnia and healthy controls: a magnetic
      resonance imaging study.
AB  - Little is known about the relation between pineal volume and insomnia. Melatonin
      promotes sleep processes and, administered as a drug, it is suitable to improve
      primary and secondary sleep disorders in humans. Recent magnetic resonance
      imaging studies suggest that human plasma and saliva melatonin levels are
      partially determined by the pineal gland volume. This study compares the pineal
      volume in a group of patients with primary insomnia to a group of healthy people
      without sleep disturbance. Pineal gland volume (PGV) was measured on the basis of
      high-resolution 3 Tesla MRI (T1-magnetization prepared rapid gradient echo) in 23
      patients and 27 controls, matched for age, gender and educational status. Volume
      measurements were performed conventionally by manual delineation of the pineal
      borders in multi-planar reconstructed images. Pineal gland volume was
      significantly smaller (P < 0.001) in patients (48.9 +/- 26.6 mm(3) ) than in
      controls (79 +/- 30.2 mm(3) ). In patients PGV correlated negatively with age (r
      = -0.532; P = 0.026). Adjusting for the effect of age, PGV and rapid eye movement
      (REM) latency showed a significant positive correlation (rS  = 0.711, P < 0.001)
      in patients. Pineal volume appears to be reduced in patients with primary
      insomnia compared to healthy controls. Further studies are needed to clarify
      whether low pineal volume is the basis or the consequence of functional sleep
      changes to elucidate the molecular pathology for the pineal volume loss in
      primary insomnia. 

PMID- 24456091
TI  - Note from Iran: Self-reported elder abuse in Qazvin, 2012.
AB  - This brief report provides a first look at self-reported instances of elder abuse
      by a sample of people 60 years and older living in Qazvin, Iran. Six hundred
      community-dwelling persons, drawn from the registry files of each health center
      in Qazin, completed questionnaires during April to October 2012. At least 80% of
      the participants reported experiencing some form of psychological abuse,
      financial abuse, and/or neglect at least once during a 2-month period. Physical
      and sexual abuse were rarely reported. Despite a strong Iranian cultural emphasis
      on respect for elders, the self-reporting of elder abuse, especially
      psychological abuse, is greater than our expectation. We recommend that health
      related policies and programs begin to identify elder abuse and neglect as a
      first step in prevention. 

PMID- 24456092
TI  - Programmable redox state of the nickel ion chain in DNA.
AB  - DNA is a nanowire in nature which chelates Ni ions and forms a conducting chain
      in its base-pairs (Ni-DNA). Each Ni ion in Ni-DNA exhibits low (Ni(2+)) or high
      (Ni(3+)) oxidation state and can be switched sequentially by applying bias
      voltage with different polarities and writing times. The ratio of low and high
      oxidation states of Ni ions in Ni-DNA represents a programmable multistate memory
      system with an added capacitive component, in which multistate information can be
      written, read, and erased. This study also indicates that the biomolecule-based
      self-organized nanostructure can be used as a template for nanodevice
      fabrication. 

PMID- 24456093
TI  - Governance of complex systems: results of a sociological simulation experiment.
AB  - Social sciences have discussed the governance of complex systems for a long time.
      The following paper tackles the issue by means of experimental sociology, in
      order to investigate the performance of different modes of governance
      empirically. The simulation framework developed is based on Esser's model of
      sociological explanation as well as on Kroneberg's model of frame selection. The
      performance of governance has been measured by means of three macro and two micro
      indicators. Surprisingly, central control mostly performs better than
      decentralised coordination. However, results not only depend on the mode of
      governance, but there is also a relation between performance and the composition
      of actor populations, which has yet not been investigated sufficiently.
      Practitioner Summary: Practitioners can gain insights into the functioning of
      complex systems and learn how to better manage them. Additionally, they are
      provided with indicators to measure the performance of complex systems. 

PMID- 24456094
TI  - Antral follicle populations and embryo production--in vitro and in vivo--of Bos
      indicus-taurus donors from weaning to yearling ages.
AB  - Interest in indicus-taurus cattle has been increasing, as these animals are
      likely to present the best characteristics of Zebu and European bovine breeds.
      The aim of this study was to compare the embryo production of indicus-taurus
      donors with high vs low antral follicle counts obtained by ovum pickup/in vitro
      production (OPU/IVP) and superovulation (SOV)/embryo collection. Braford females
      at weaning age (3/8 Nelore * 5/8 Hereford, n = 137, 9 +/- 1 month old) were
      subjected to six serial ovarian ultrasonographs and were assigned to two groups
      according to the number of antral follicles >= 3 mm as follows: G-High antral
      follicular count (AFC, n = 20, mean >= 40 follicles) and G-Low AFC (n = 20, mean
      <= 10 follicles). When the females (n = 40) reached 24 months of age, they were
      subjected to both OPU/IVP and SOV/embryo collection. The average number of
      follicles remained highly stable throughout all of the ultrasound evaluations
      (range 0.90-0.92). The mean number of COCs recovered (36.90 +/- 13.68 vs 5.80 +/-
      3.40) was higher (p < 0.05) for females with high AFC, resulting in higher (p <
      0.05) numbers of total embryos among females with high vs low AFC (6.10 +/- 4.51
      vs 0.55 +/- 0.83). The mean number of embryos per collection was also higher (p <
      0.05) for G-High vs G-Low (6.95 +/- 5.34 vs 1.9 +/- 2.13). We conclude that a
      single ultrasound performed at pre-pubertal ages to count antral follicles can be
      used as a predictor of embryo production following IVP and SOV/embryo collection
      in indicus-taurus females.

PMID- 24456095
TI  - Kidney growth and renal functions under the growth hormone replacement therapy in
      children.
AB  - OBJECTIVE: The aim of this study was to investigate the kidney growth and renal
      functions in children receiving recombinant human growth hormone (rhGH)
      treatment. MATERIALS AND METHODS: A total of 37 children who received rhGH for
      1.5 years before the study was started and 48 healthy controls were included at
      first evaluation. Hormone levels were determined and kidney sizes were measured
      by ultrasound. Kidney functions were assessed by serum creatinine and estimated
      glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients
      were re-assessed. RESULTS: Kidney sizes were found to be lower in rhGH received
      children compared with controls at first evaluation (p<0.05). Significant
      positive correlations were found between anthropometric measurements and kidney
      length and kidney volume (p<0.05). Height was the most significant predictor of
      kidney volume in rhGH received children (p<0.001). After 3-years of follow-up
      significantly increases were found in kidney length and volume compared with the
      first measurements (p<0.05). Increase percentage of body height was similar to
      increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%,
      respectively, p>0.05). Although no abnormal renal function test results were
      found at first and second evaluations; rhGH received children had significantly
      lower eGFR, at first evaluation, compared with controls; however, renal functions
      significantly increased after 3 years of follow-up (p<0.05). CONCLUSIONS: In
      conclusion, effect rhGH treatment on kidney growth is parallel to growth in body
      height and other visceral organs. A 3-years rhGH treatment resulted in
      significant increases in renal functions.

PMID- 24456097
TI  - Sexual dysfunction among Sri Lankan adults: effect of diabetes mellitus.

PMID- 24456096
TI  - Specific ions modulate diffusion dynamics of hydration water on lipid membrane
      surfaces.
AB  - Effects of specific ions on the local translational diffusion of water near large
      hydrophilic lipid vesicle surfaces were measured by Overhauser dynamic nuclear
      polarization (ODNP). ODNP relies on an unpaired electron spin-containing probe
      located at molecular or surface sites to report on the dynamics of water protons
      within ~10 A from the spin probe, which give rise to spectral densities for
      electron-proton cross-relaxation processes in the 10 GHz regime. This pushes
      nuclear magnetic resonance relaxometry to more than an order of magnitude higher
      frequencies than conventionally feasible, permitting the measurement of water
      moving with picosecond to subnanosecond correlation times. Diffusion of water
      within ~10 A of, i.e., up to ~3 water layers around the spin probes located on
      hydrophilic lipid vesicle surfaces is ~5 times retarded compared to the bulk
      water translational diffusion. This directly reflects on the activation barrier
      for surface water diffusion, i.e., how tightly water is bound to the hydrophilic
      surface and surrounding waters. We find this value to be modulated by the
      presence of specific ions in solution, with its order following the known
      Hofmeister series. While a molecular description of how ions affect the hydration
      structure at the hydrophilic surface remains to be answered, the finding that
      Hofmeister ions directly modulate the surface water diffusivity implies that the
      strength of the hydrogen bond network of surface hydration water is directly
      modulated on hydrophilic surfaces.

PMID- 24456098
TI  - Positive affect facilitates task switching in the dimensional change card sort
      task: implications for the shifting aspect of executive function.
AB  - Using the modified Dimensional Change Card Sort task, we examined the influence
      of positive affect on task switching by inspecting various markers for the costs,
      including restart cost, switch cost and mixing cost. Given that the executive
      control processes that underlie switching performance--i.e., inhibition or
      shifting--are distinct from the component processes that underlie non-switching
      performance--i.e., stimulus evaluation, resource allocation or response execution
      -we hypothesised that if positive affect facilitates task switching via executive
      control processes, rather than via component processes, positive affect would
      reduce both switch and restart costs, but not mixing cost, because both switch
      and restart costs rely on executive processes, while mixing cost imposes only
      minimal demands on executive processes. We found beneficial effects of positive
      affect on both restart and switch costs, but not on mixing costs. These results
      suggest that positive affect improves switching abilities via executive processes
      rather than via component processes.

PMID- 24456100
TI  - Effect of cationic and anionic surfactants on the application of calcium
      carbonate nanoparticles in paper coating.
AB  - Modification of calcium carbonate particles with surfactant significantly
      improves the properties of the calcium carbonate coating on paper. In this study,
      unmodified and CTAB (hexadecyltetramethylammonium bromide)- and oleate-modified
      calcium carbonate nanoparticles were prepared using the wet carbonation technique
      for paper coating. CTAB (cationic surfactant) and sodium oleate (anionic
      surfactant) were used to modify the size, morphology, and surface properties of
      the precipitated nanoparticles. The obtained particles were characterized using X
      ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, zeta
      potential measurements, thermal gravimetric analysis (TGA), and transmission
      electron microscopy (TEM). Coating colors were formulated from the prepared
      unmodified and modified calcium carbonates and examined by creating a thin
      coating layer on reference paper. The effect of calcium carbonate particle size
      and surface modification on paper properties, such as coating thickness, coating
      weight, surface roughness, air permeability, brightness, whiteness, opacity, and
      hydrophobicity, were investigated and compared with commercial ground (GCC)
      calcium carbonate-coated papers. The results show that the obtained calcium
      carbonate nanoparticles are in the calcite phase. The morphology of the prepared
      calcium carbonate nanoparticles is rhombohedral, and the average particle
      diameter is less than 100 nm. Compared to commercial GCC, the use of unmodified
      and CTAB- and oleate-modified calcium carbonate nanoparticles in paper coating
      improves the properties of paper. The highest measured paper properties were
      observed for paper coated with oleate-modifed nanoparticles, where an increase in
      smoothness (decrease in paper roughness) (+23%), brightness (+1.3%), whiteness
      (+2.8%), and opacity (+2.3%) and a decrease in air permeability (-26%) was
      obtained with 25% less coat weight. The water contact angle at a drop age time of
      10 min was about 112 degrees  for the paper coated with oleate-modified
      nanoparticles and 42 degrees  for paper coated with CTAB-modified nanoparticles
      compared to 104 degrees  for GCC-coated paper. 

PMID- 24456101
TI  - Melanoma-associated antigen-A3 vaccination in the treatment of non-small-cell
      lung cancer.
AB  - INTRODUCTION: Lung cancer is a common health problem with a bad prognosis,
      despite recent advances in its treatment. Antigen-specific immunotherapy implies
      the administration of tumor-specific antigens with an immunostimulant to induce a
      powerful antitumor immune response, which has shown to be capable of eliminating
      tumor cells. Melanoma-associated antigen (MAGE) A3 is a good antigen to use in
      antigen-specific immunotherapy, since it is aberrantly expressed in cancer cells,
      but not expressed in normal tissue, except in germline and placental cells. AREAS
      COVERED: Trials have been performed with the MAGE-A3 vaccine in the adjuvant
      setting after resection of non-small-cell lung cancer. They have shown that the
      MAGE-A3 vaccine is safe and well tolerated, with promising signs of clinical
      benefit, especially in patients expressing a specific gene signature. Outcome
      data are currently expected of a large Phase III randomized controlled trial in
      the same setting. EXPERT OPINION: The future is hopeful for antigen-specific
      immunotherapy in general and MAGE-A3 vaccine in specific. Further research needs
      to identify new tumor-specific antigens, more potent adjuvants and genetic
      profiles suggestive of a better response toward antigen-specific immunotherapy.
      The MAGE-A3 vaccine has to be investigated in other settings than the adjuvant
      one and in other tumor types expressing MAGE-A3.

PMID- 24456103
TI  - Catastrophic thrombosis in idiopathic hypereosinophilic syndrome.

PMID- 24456102
TI  - Anatomy and transcript profiling of gynoecium development in female sterile
      Brassica napus mediated by one alien chromosome from Orychophragmus violaceus.
AB  - BACKGROUND: The gynoecium is one of the most complex organs of angiosperms
      specialized for seed production and dispersal, but only several genes important
      for ovule or embryo sac development were identified by using female sterile
      mutants. The female sterility in oilseed rape (Brassica napus) was before found
      to be related with one alien chromosome from another crucifer Orychophragmus
      violaceus. Herein, the developmental anatomy and comparative transcript profiling
      (RNA-seq) for the female sterility were performed to reveal the genes and
      possible metabolic pathways behind the formation of the damaged gynoecium.
      RESULTS: The ovules in the female sterile Brassica napus with two copies of the
      alien chromosomes (S1) initiated only one short integument primordium which
      underwent no further development and the female gametophyte development was
      blocked after the tetrad stage but before megagametogenesis initiation. Using
      Brassica_ 95k_ unigene as the reference genome, a total of 28,065 and 27,653
      unigenes were identified to be transcribed in S1 and donor B. napus (H3),
      respectively. Further comparison of the transcript abundance between S1 and H3
      revealed that 4540 unigenes showed more than two fold expression differences.
      Gene ontology and pathway enrichment analysis of the Differentially Expressed
      Genes (DEGs) showed that a number of important genes and metabolism pathways were
      involved in the development of gynoecium, embryo sac, ovule, integuments as well
      as the interactions between pollen and pistil. CONCLUSIONS: DEGs for the ovule
      development were detected to function in the metabolism pathways regulating
      brassinosteroid (BR) biosynthesis, adaxial/abaxial axis specification, auxin
      transport and signaling. A model was proposed to show the possible roles and
      interactions of these pathways for the sterile gynoecium development. The results
      provided new information for the molecular mechanisms behind the gynoecium
      development at early stage in B. napus.

PMID- 24456104
TI  - Acute, symptomatic catheter-associated DVT with mobile, intra-cardiac thrombus in
      an infant with severe haemophilia A.

PMID- 24456105
TI  - Is methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphism related
      with varicocele risk?
AB  - Varicocele is one of the main reasons for male infertility the exact aetiology of
      which remains unclear. Methylenetetrahydrofolate reductase (MTHFR) is important
      for DNA synthesis and methylation, which has a key role during spermatogenesis.
      Numerous literature suggests that the MTHFR polymorphism may be genetic risk
      factors for male infertility. In this study, we evaluated C677T and A1298C MTHFR
      gene polymorphism frequency in patients with varicocele and normal men. A total
      of 107 varicocele patients and 109 fertile healthy individuals were included.
      Genotyping of the MTHFR gene in C677T and A1298C base pairs carried out by using
      real-time PCR technique and afterwards, the statistical analysis accomplished.
      There is a statistical difference for the frequency of 1298AA genotype in
      patients with varicocele compared with normal controls (P = 0.0051, OR = 2.2750).
      Instead, subsequently, 1298/A allel frequency in patient group was significantly
      higher in comparison with control group (P = 0.0174). According to our results,
      1298AA genotype in MTHFR gene raises the risk of varicocele approximately 2.3
      times more compared with men carrying other genotypes. The results show that
      genetic factors have an important role in the molecular basis of varicocele.

PMID- 24456106
TI  - Selective and reversible inhibitors of ubiquitin-specific protease 7: a patent
      evaluation (WO2013030218).
AB  - The invention described in this review (WO2013030218) relates to compounds based
      on the quinazolin-4-one scaffold, their process of preparation and applications
      to inhibit the ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme
      (DUB), which is considered a potentially important new drug target for treating
      cancer and immunological disorders. Data are presented indicating that these
      small-molecule compounds are useful as selective and reversible inhibitors of
      USP7 in vitro and also in a cellular context, although the panel of other enzymes
      tested was limited. The synthesis strategy allows for the generation of a
      considerable variety of compounds, although similar properties of selective USP7
      inhibition were reported for other related compound classes, thereby increasing
      the complexity of the patenting process. However, structural patterns that
      contribute to the selectivity of USP7 and other DUB enzyme inhibition are
      starting to emerge. Practical implications involve the treatment of cancer,
      neurodegenerative diseases, immunological disorders, diabetes, bone and joint
      diseases, cardiovascular diseases and viral and bacterial infections. The quality
      of these findings and a comparison to other compound classes with similar
      properties, as well as the potential for further development toward clinical
      exploitation are discussed. 

PMID- 24456107
TI  - Natural history of atypical and equivocal melanocytic lesions in children: an
      observational study of 19 cases.
AB  - Digital dermoscopy follow-up helps to identify patterns of change typical of
      common atypical nevi and early melanoma and improves the follow-up of patients
      with atypical nevi. We report the morphologic changes observed over time in 19
      atypical or equivocal acquired melanocytic nevi that underwent dermoscopic follow
      up. Two observers retrospectively examined digitalized dermoscopic images of 19
      atypical melanocytic nevi from 15 children and young adults (median age 12 years,
      range 3-26 years). The images were assessed for global dermoscopic patterns at
      baseline and after a median 25-month (range 6-138 mos) follow-up. Ten (52.6%)
      nevi changed and nine (47.4%) retained a stable dermoscopic pattern. Of the 10
      changing lesions, 2 of 4 homogeneous nevi evolved into a reticular pattern and 2
      into a mixed pattern; 1 of 2 nevi with a mixed pattern evolved into a homogeneous
      nevus and 1 into a regressing nevus; 1 of 2 nevi with "other" patterns, such as
      negative pigment network and peppering throughout the lesion, evolved into a
      mixed nevus and 1 into a regressing nevus; 1 globular nevus evolved into a mixed
      pattern; and 1 starburst nevus evolved into a homogeneous nevus. The most
      striking results of our study were that atypical nevi can evolve into common nevi
      or they can regress, as documented by long-term dermoscopic follow-up. In
      children and young adults, dermoscopic follow-up of atypical nevi might be a
      valid alternative to surgical excision and enables us to achieve new insights
      into the natural history of these nevi.

PMID- 24456108
TI  - Allergic airway diseases in a tropical urban environment are driven by dominant
      mono-specific sensitization against house dust mites.
AB  - BACKGROUND: Southeast Asian populations are increasingly affected by allergic
      airway diseases. Etiology and specific causes, however, are still unknown. The
      aim of this study is therefore to identify allergens and risk factors for the
      high prevalence of allergic airway disease in the tropical urban environment.
      METHODS: Symptoms of allergic rhinitis (AR), asthma, and allergic dermatitis were
      recorded in two independent cohorts of 576 and 7373 ethnic Chinese individuals
      living in Singapore. Reactivity against common allergens was determined by skin
      prick tests (SPT); specific immunoglobulin E (sIgE) titers against 12 common
      allergens, as well as total serum IgE (tIgE), were measured in the smaller
      cohort. RESULTS: Immunoglobulin E sensitization was almost exclusively directed
      against house dust mite (HDM) allergens. More than 80% of individuals were HDM
      sIgE positive. Of these, less than 30% also had sIgE for other allergens, and
      similarly, few of the HDM-sIgE-negative individuals reacted to other allergens.
      Titers for HDM-sIgE were 8-30 times higher than other non-HDM allergen titers and
      correlated directly with total serum tIgE levels. Migrants from nontropical
      countries typically arrived with low or undetectable HDM-sIgE but developed
      substantial titers in a time-dependent fashion. Importantly, prolonged stay in
      Singapore also resulted in the manifestation of AR and asthma symptoms,
      contributing to some of the highest national prevalence rates worldwide.
      CONCLUSION: In a tropical urban environment, the allergic response is dominated
      by a single allergen class. The mono-specific IgE sensitization against HDM
      translates into increased prevalence of allergic airway diseases, which now
      impact a large proportion of the population in Singapore.

PMID- 24456109
TI  - Validity of the Cantonese Chinese Montreal Cognitive Assessment in Southern
      Chinese.
AB  - AIM: The objective of the present study was to investigate the reliability and
      the validity of the Cantonese Chinese Montreal Cognitive Assessment (MoCA) as a
      brief screening tool of amnestic mild cognitive impairment (aMCI) and Alzheimer's
      disease (AD) in Southern Chinese older adults. METHODS: Cognitively normal, aMCI
      and AD Cantonese-speaking Chinese older adults were recruited from a memory
      clinic and the community. The English MoCA was translated into Cantonese Chinese
      and then back-translated. We then evaluated the content validity, reliability,
      sensitivity and specificity of the Chinese Cantonese MoCA. RESULTS: We recruited
      115 cognitively normal controls, 87 aMCI and 64 AD patients. Only education was
      positively correlated with the Cantonese MoCA score (r = 0.46, P < 0.001). The
      Chinese Cantonese MoCA had a high internal consistency with a Cronbach's alpha of
      0.85. In the test-retest reliability assessment, the intraclass correlation
      coefficient (ICC) was 0.95 (P < 0.001). The ICC for the interrater reliability
      was 0.96 (P < 0.001). Receiving operating characteristic curve analyses showed an
      area under the curve of 0.85 and 0.99 for aMCI and AD, respectively (both P <
      0.001). The optimal cut-off score for detection of aMCI was 22/23, which yielded
      a sensitivity and specificity of 78% and 73%, respectively. The optimal cut-off
      score for detection of AD was 19/20, which gave sensitivity and specificity of
      94% and 92%, respectively. CONCLUSION: The Cantonese Chinese MoCA is a consistent
      and reliable instrument. In terms of its validity, the MoCA is better in the
      detection of AD than aMCI in Cantonese-speaking Chinese persons. It is only fair
      for the screening of aMCI.

PMID- 24456111
TI  - Associations between sleep habits and mental health status and suicidality in a
      longitudinal survey of monozygotic twin adolescents.
AB  - Several epidemiological studies have indicated that there is a relationship
      between sleep habits, such as sleep duration, bedtime and bedtime regularity, and
      mental health status, including depression and anxiety in adolescents. However,
      it is still to be clarified whether the relationship is direct cause-and-effect
      or mediated by the influence of genetic and other traits, i.e. quasi-correlation.
      To examine this issue, we conducted a twin study using a total of 314 data for
      monozygotic twins from a longitudinal survey of sleep habits and mental health
      status conducted in a unified junior and senior high school (grades 7-12),
      located in Tokyo, Japan. Three-level hierarchical linear model analysis showed
      that both bedtime and sleep duration had significant associations with the
      Japanese version of the 12-item General Health Questionnaire (GHQ-12) score,
      suicidal thoughts and the experience of self-harm behaviours when genetic factors
      and shared environmental factors, which were completely shared between co-twins,
      were controlled for. These associations were statistically significant even after
      controlling for bedtime regularity, which was also associated significantly with
      the GHQ-12 score. These suggest that the associations between sleep habits and
      mental health status were still statistically significant after controlling for
      the influence of genetic and shared environmental factors of twins, and that
      there may be a direct cause-and-effect in the relationship in adolescents. Thus,
      late bedtime and short sleep duration could predict subsequent development of
      depression and anxiety, including suicidal or self-injury risk. This suggests
      that poor mental health status in adolescents might be improved by health
      education and intervention concerning sleep and lifestyle habits. 

PMID- 24456112
TI  - Determination of the composition for binary mixtures of polyanions: the case of
      mixed solutions of alginate and hyaluronan.

PMID- 24456113
TI  - Comparison of in vitro developmental competence of cloned caprine embryos using
      donor karyoplasts from adult bone marrow mesenchymal stem cells vs ear fibroblast
      cells.
AB  - The aim of this study was to produce cloned caprine embryos using either caprine
      bone marrow-derived mesenchymal stem cells (MSCs) or ear fibroblast cells (EFCs)
      as donor karyoplasts. Caprine MSCs were isolated from male Boer goats of an
      average age of 1.5 years. To determine the pluripotency of MSCs, the cells were
      induced to differentiate into osteocytes, chondrocytes and adipocytes.
      Subsequently, MSCs were characterized through cell surface antigen profiles using
      specific markers, prior to their use as donor karyoplasts for nuclear transfer.
      No significant difference (p > 0.05) in fusion rates was observed between MSCs
      (87.7%) and EFCs (91.3%) used as donor karyoplasts. The cleavage rate of cloned
      embryos derived with MSCs (87.0%) was similar (p > 0.05) to those cloned using
      EFCs (84.4%). However, the in vitro development of MSCs-derived cloned embryos
      (25.3%) to the blastocyst stage was significantly higher (p < 0.05) than those
      derived with EFCs (20.6%). In conclusion, MSCs could be reprogrammed by caprine
      oocytes, and production of cloned caprine embryos with MSCs improved their in
      vitro developmental competence, but not in their fusion and cleavage rate as
      compared to cloning using somatic cells such as EFCs.

PMID- 24456114
TI  - Outcomes of stage 1-5 chronic kidney disease in Mainland China.
AB  - OBJECTIVE: This study aims to quantify and compare the risks of death and end
      stage renal disease (ESRD) in a prospective cohort of patients with chronic
      kidney disease (CKD) stages 1-5 under renal management clinic at Peking
      University Third Hospital and to evaluate the risk factors associated with these
      two outcomes. METHOD: This was a prospective cohort study. Finally, 1076 patients
      at CKD stage 1-5 short of dialysis were recruited from renal management clinic.
      Patients were monitored for up to Dec, 2011 or until ESRD and death. Glomerular
      filtration rate was estimated (eGFR) according to the using the CKD Epidemiology
      Collaboration (CKD-EPI) formula. RESULTS: At the end of follow-up, 111 patients
      (10.1%) developed ESRD (initiated dialysis or kidney transplantation (ESRD)) and
      24 patients (2.2%) had died. There were more ESRD occurrence rate in patients
      with baseline diabetic nephropathy, lower eGFR, hemoglobin <100 g/L and 24 h
      urinary protein excretion >= 3.0 g. By multivariate Cox regression model, having
      heavy proteinuria and CKD stage were the risk factors of ESRD. For all-cause
      mortality, the most common cause was cardiovascular disease, followed by
      infectious disease and cancer. But we failed to conclude any significant variable
      as risk factors for mortality in multivariate analysis. CONCLUSIONS: Our study
      indicated that baseline diabetic nephropathy, lower hemoglobin level, lower
      baseline GFR and heavy proteinuria were the risk factors of ESRD. In this CKD
      cohort, patients were more likely to develop ESRD than mortality, and
      cardiovascular mortality was the leading cause of death, and then followed by
      infectious diseases and cancer in this population.

PMID- 24456115
TI  - Photopharmacology: beyond proof of principle.
AB  - Pharmacotherapy is often severely hindered by issues related to poor drug
      selectivity, including side effects, environmental toxicity, and the emergence of
      resistance. Lack of selectivity is caused by the inability to control drug
      activity in time and space. Photopharmacology aims at solving this issue by
      incorporating photoswitchable groups into the molecular structure of bioactive
      compounds. These switching units allow for the use of light as an external
      control element for pharmacological activity, which can be delivered with very
      high spatiotemporal precision. This Perspective presents the reader with the
      current state and outlook on photopharmacology. In particular, the principles
      behind photoregulation of bioactivity, the challenges of molecular design, and
      the possible therapeutic scenarios are discussed. 

PMID- 24456117
TI  - Improved oral delivery of resveratrol using proliposomal formulation:
      investigation of various factors contributing to prolonged absorption of
      unmetabolized resveratrol.
AB  - OBJECTIVES: The objective of this study was to design lipid-based formulation to
      enhance the absorption of unmetabolized resveratrol (RSV) over adequate time and
      investigate various factors that contribute to prolonged absorption of RSV.
      METHODS: Proliposomal formulations containing distearoyl phosphatidyl choline
      (DSPC) with or without cholesterol were prepared and evaluated. The liposomes
      obtained from hydration of proliposomal mixture were evaluated for size, zeta,
      physical appearance and entrapment. The integrity of liposomes in bile salt
      solution and solubility of RSV in sodium taurocholate solution in the presence of
      various concentrations of DSPC were evaluated to assess the stability and in
      varied gastrointestinal conditions. Finally, oral pharmacokinetic studies of
      liposomal dispersions in comparison with RSV solution were evaluated. RESULTS:
      Results revealed that spontaneous formation of liposomes did not occur upon
      hydration of RSV: DSPC proliposomes rather showed tendency to form loose cotton
      like aggregates. Cholesterol aided in the formation of stable liposomes with
      large negative zeta potential. Release of RSV from liposomes in the presence of
      taurocholate was dependent on the amount and type of total lipid. Liposomes
      without cholesterol showed faster release, and release increased as the amount of
      DSPC in the formulation increased. Solubility studies indicated that DSPC
      increases the solubility of RSV in the presence of sodium taurocholate, and
      corroborates that bilayer assembly is disrupted because of interaction between
      RSV and DSPC. Mixture of RSV:DSPC:Chol at 1:0.25:0.25 formed stable colloidal
      dispersion with zeta potential -22 and released only 20 - 23% of entrapped RSV
      when incubated with 20 mM sodium taurocholate. Pharmacokinetic profile revealed
      that AUC and Cmax were twofold higher than plain RSV. CONCLUSION: The
      proliposomal formulation optimized by considering various physicochemical factors
      and simulated in vitro testing result in significant improvement rate and extent
      of absorption of unmetabolized RSV.

PMID- 24456118
TI  - Carrier erythrocytes: recent advances, present status, current trends and future
      horizons.
AB  - INTRODUCTION: Carrier erythrocytes, thanks to their main advantages, including
      biocompatibility, biodegradability, immunocompatibility, simple and well-known
      structure and physiology, availability for sampling and versatility in loading
      and use, have been studied as cellular carriers for delivery of drugs and other
      bioactive agents for more than three decades. Based on this body of knowledge and
      recent advances in this field, and with the help of novel multidisciplinary
      sciences and technologies, it seems that this field is becoming renowned and
      experiencing an outstanding turning point in its developmental history. AREAS
      COVERED: In this trendy and timely review, following a short historical review of
      the story of erythrocytes from oxygen delivery to drug delivery and evaluation of
      the present status of these biocarriers, recent advances and current
      experimental, technological and clinical trends, as well as future horizons, and,
      in particular, translation-prone strategies, are going to be discussed in detail.
      EXPERT OPINION: Despite the challenging developmental history of carrier
      erythrocytes, they now stand closer to clinical use and market entrance due to
      their unique advantages in drug delivery, proven by recently reported success
      stories in late-stage clinical trials and progresses made in biotechnology,
      nanotechnology and biomaterials fields. Translation-prone approaches, like in
      vivo loading of circulating erythrocytes or semiautomatic loading of
      erythrocytes, and more realistic study designs by focusing on clinical needs that
      have not been responded to or erythrocyte biology/fate-inspired study design are
      among the main trends being focused on by pioneer research groups active in this
      field of drug delivery.

PMID- 24456116
TI  - Design, synthesis, and characterization of alpha-ketoheterocycles that
      additionally target the cytosolic port Cys269 of fatty acid amide hydrolase.
AB  - A series of alpha-ketooxazoles incorporating electrophiles at the C5 position of
      the pyridyl ring of 2 (OL-135) and related compounds were prepared and examined
      as inhibitors of fatty acid amide hydrolase (FAAH) that additionally target the
      cytosolic port Cys269. From this series, a subset of the candidate inhibitors
      exhibited time-dependent FAAH inhibition and noncompetitive irreversible
      inactivation of the enzyme, consistent with the targeted Cys269 covalent
      alkylation or addition, and maintained or enhanced the intrinsic selectivity for
      FAAH versus other serine hydrolases. A preliminary in vivo assessment
      demonstrates that these inhibitors raise endogenous brain levels of anandamide
      and other FAAH substrates upon intraperitoneal (i.p.) administration to mice,
      with peak levels achieved within 1.5-3 h, and that the elevations of the
      signaling lipids were maintained >6 h, indicating that the inhibitors effectively
      reach and remain active in the brain, inhibiting FAAH for a sustained period. 

PMID- 24456119
TI  - Automated tracking of quantitative parameters from single line scanning of vocal
      folds: a case study of the 'messa di voce' exercise.
AB  - This article presents a novel application of the 'single line scanning' of the
      vocal fold vibrations (kymography) in singing pedagogy, particularly in a
      specific technical voice exercise: the 'messa di voce'. It aims at giving the
      singer relevant and valid short-term feedback. A user-friendly automatic analysis
      program makes possible a precise, immediate quantification of the essential
      physiological parameters characterizing the changes in glottal impedance,
      concomitant with the progressive increase and decrease of the lung pressure. The
      data provided by the program show a strong correlation with the hand-made
      measurements. Additional measurements such as subglottic pressure and flow
      glottography by inverse filtering can be meaningfully correlated with the data
      obtained from the kymographic images. 

PMID- 24456120
TI  - Femtosecond laser treatment for the design of electro-insulating superhydrophobic
      coatings with enhanced wear resistance on glass.
AB  - Femtosecond laser treatment of a glass surface was used to fabricate a multimodal
      roughness having regular surface ripples with a period of a few micrometers
      decorated by aggregates of nearly spherical nanoparticles. UV-ozone treatment
      followed by chemisorption of the appropriate functional fluorosilanes onto the
      textured surface makes it possible to fabricate a superhydrophobic coating with a
      specific surface resistance on the order of petaohms on a glass surface. The main
      advantage of the fabricated coating under severe operating conditions with
      abrasion loads is the significant durability of its electro-insulating
      properties. The longevity of the high surface resistivity, even on long-term
      contact with a water vapor-saturated atmosphere, is directly related to the
      peculiarities of the surface texture and ripple structure. 

PMID- 24456121
TI  - Traits associated with winter wheat grain yield in Central and West Asia.
AB  - Improved adaptation of winter wheat (Triticum aestivum L.) to drought and heat
      may be influenced by days to heading, plant height, biomass, canopy temperature
      (CT) at grain filling, and rate of senescence. This study shows that, under
      supplemental irrigation or rainfed conditions, days to heading and plant height
      together explain up to 68% of grain yield (GY) variation, and these associations
      were further confirmed in several locations across West and Central Asia. Days to
      heading can be slightly reduced below that of check line Karahan to further
      improve GY while avoiding the effect of late frosts. Plant height has been
      decreased in recent germplasm, but further reductions below that of check line
      Karahan could still improve GY in a wide range of environments. However, in
      Iranian sites, taller genotypes showed better adaptation with higher biomass and
      increased reserves for grain filling. Canopy temperature and rate senescence were
      not associated with GY. A normalized difference vegetation index, used to
      estimate biomass (Feekes stages 4-5), had intermediate heritability across
      environments and correlated positively with GY under low plant density and should
      be explored further as a tool for early selection. 

PMID- 24456122
TI  - Complete response of monoblastic myeloid sarcoma with FIP1L1- PDGFRA
      rearrangement to imatinib monotherapy.

PMID- 24456123
TI  - Successful ICSI in an azoospermic and kidney transplant man with type 1 primary
      hyperoxaluria and first histopathological testicular findings described in the
      literature.
AB  - In this report, we describe for the first time a pregnancy using sperm retrieved
      from an azoospermic man with kidney transplant due to type I primary
      hyperoxaluria. It is the first case that we were able to find in the literature
      for both male infertility and hystopathologic findings. 

PMID- 24456125
TI  - A haemophilia disease management programme targeting cost and utilization of
      specialty pharmaceuticals.
AB  - The high cost of clotting factor concentrate (CFC) used to treat haemophilia and
      von Willebrand disease (VWD) attracts health plans' attention for cost management
      strategies such as disease management programmes (DMPs). In 2004, Indiana's high
      risk insurance health plan, the Indiana Comprehensive Health Insurance
      Association, in partnership with the Indiana Hemophilia and Thrombosis Center
      developed and implemented a DMP for beneficiaries with bleeding disorders. This
      report evaluates the effectiveness of the DMP 5 years post implementation, with
      specific emphasis on the cost of CFC and other medical expenditures by severity
      of disease. A pre/post analysis was used. The main evaluation measures were total
      cost, total outpatient CFC IU dispensed and adjusted total outpatient CFC cost.
      Summary statistics and mean and median plots were calculated. Overall, 1000 non
      parametric bootstrap replicates were created and percentile confidence limits for
      95% confidence intervals (CI) are reported. Mean emergency department (ED) visits
      and mean and median duration of hospitalizations are also reported. The DMP was
      associated with a significant decrease in mean annualized total cost including
      decreased CFC utilization and cost in most years in the overall group, and
      specifically in patients with severe haemophilia. Patients with mild and moderate
      haemophilia contributed little to overall programme expenditures. This specialty
      health care provider-administered DMP exemplifies the success of targeted
      interventions developed and implemented through a health care facility expert in
      the disease state to curb the cost of specialty pharmaceuticals in conditions
      when their expenditures represent a significant portion of total annual costs of
      care. 

PMID- 24456126
TI  - Quality of life in older people with dementia: a multilevel study of individual
      attributes and residential care center characteristics.
AB  - AIM: To analyze how the characteristics of institutionalized older people with
      dementia and residential care centers are associated with the individual's
      quality of life (QoL). METHODS: Data were collected from a survey carried out on
      525 elderly people aged 60 years or older in 14 nursing care homes across Spain.
      Multilevel linear analysis to assess the differences in QoL level between centers
      and individuals was carried out. RESULTS: The characteristics of the individuals
      that were associated with a higher QoL were functional independence, health
      status and gathering with family, friends or neighbors. In contrast, higher
      levels of dementia, depression and the length of institutionalization had a
      negative effect on QoL. In relation to the residential care center
      characteristics, the availability of geriatricians was associated with higher
      QoL, compared with those centers with no geriatricians on staff. In addition,
      public centers (public ownership and publicly-funded residents) were also
      associated with higher QoL than private/mixed centers. The multilevel analysis
      showed that the 16.4% of the differences in QoL was related to residence factors.
      CONCLUSION: These results reflect the importance of the functional, social,
      mental and residential dimensions in the QoL of older adults with dementia.
      Actions devoted to improving these key dimensions would contribute to promote the
      well-being of this vulnerable population.

PMID- 24456127
TI  - Multibreed genome wide association can improve precision of mapping causative
      variants underlying milk production in dairy cattle.
AB  - BACKGROUND: Genome wide association studies (GWAS) in most cattle breeds result
      in large genomic intervals of significant associations making it difficult to
      identify causal mutations. This is due to the extensive, low-level linkage
      disequilibrium within a cattle breed. As there is less linkage disequilibrium
      across breeds, multibreed GWAS may improve precision of causal variant mapping.
      Here we test this hypothesis in a Holstein and Jersey cattle data set with 17,925
      individuals with records for production and functional traits and 632,003 SNP
      markers. RESULTS: By using a cross validation strategy within the Holstein and
      Jersey data sets, we were able to identify and confirm a large number of QTL. As
      expected, the precision of mapping these QTL within the breeds was limited. In
      the multibreed analysis, we found that many loci were not segregating in both
      breeds. This was partly an artefact of power of the experiments, with the number
      of QTL shared between the breeds generally increasing with trait heritability.
      False discovery rates suggest that the multibreed analysis was less powerful than
      between breed analyses, in terms of how much genetic variance was explained by
      the detected QTL. However, the multibreed analysis could more accurately pinpoint
      the location of the well-described mutations affecting milk production such as
      DGAT1. Further, the significant SNP in the multibreed analysis were significantly
      enriched in genes regions, to a considerably greater extent than was observed in
      the single breed analyses. In addition, we have refined QTL on BTA5 and BTA19 to
      very small intervals and identified a small number of potential candidate genes
      in these, as well as in a number of other regions. CONCLUSION: Where QTL are
      segregating across breed, multibreed GWAS can refine these to reasonably small
      genomic intervals. However, such QTL appear to represent only a fraction of the
      genetic variation. Our results suggest a significant proportion of QTL affecting
      milk production segregate within rather than across breeds, at least for Holstein
      and Jersey cattle.

PMID- 24456128
TI  - Breast irradiation causes pallor in the nipple-areolar complex in women with
      Celtic skin type (result from the St. George and Wollongong randomised breast
      boost trial).
AB  - INTRODUCTION: The nipple-areolar complex (NAC) has special histological
      properties with higher melanocyte concentration than breast skin. To date, there
      are no data describing the late effects on the NAC following breast-conserving
      therapy (BCT). This study evaluated colour changes in the NAC in patients treated
      with breast-conserving surgery and adjuvant radiotherapy after 5 years. METHODS:
      Digital photographs obtained at 5 years following breast irradiation from the St.
      George and Wollongong (SGW) trial (NCT00138814) were evaluated by five experts
      using an iPad(r) (Apple Inc., Cupertino, CA, USA) application specifically
      created for this study. The SGW trial randomised 688 patients with Tis-2, N0-1,
      M0 carcinoma to the control arm of 50 Gy in 25 fractions and boost arm of 45 Gy
      in 25 fractions and 16 Gy in 8 fractions electron boost. RESULTS: A total of
      141/372 (38%) patients had altered NAC (86% lighter, 10% darker). Patients with
      Celtic skin type had increased likelihood of having an altered NAC (odds ratio
      (OR), 1.75 (CI 1.1-2.7, P = 0.011)). On subgroup analysis, those with Celtic skin
      type receiving biologically equivalent dose (BED) Gy3 >= 80 Gy had OR of 3.03
      (95% CI 1.2-7.5, P = 0.016) for having altered colour. There was a dose response
      with more profound changes seen in the NAC compared with irradiated breast skin
      if BED Gy3 >= 80 Gy with OR of 2.42 (95% CI 1.1-5.6, P = 0.036). CONCLUSION: In
      this Caucasian BCT population, over 30% of patients developed lighter NAC and
      more commonly in women with Celtic skin type. The degree of this effect increased
      with higher radiation dose.

PMID- 24456129
TI  - Modification of cellulose nanofibrils with luminescent carbon dots.
AB  - Films and hydrogels consisting of cellulose nanofibrils (CNF) were modified by
      covalent EDC/NHS coupling of luminescent, water-dispersible carbon dots (CDs).
      Quartz crystal microgravimetry with dissipation monitoring (QCM-D) and surface
      plasmon resonance (SPR) were used to investigate the attachment of CDs on
      carboxymethylated CNF (CM-CNF). As the first reported use of CD in nanocellulose
      products, we provide proof-of-concept for the synthesis of transparent and
      fluorescent nanopaper and for its tunable luminescence as confirmed by confocal
      microscopy imaging. 

PMID- 24456130
TI  - An unusual cluster of circumscribed juvenile pityriasis rubra pilaris cases.
AB  - Circumscribed juvenile pityriasis rubra pilaris (PRP) is an uncommon dermatosis.
      We describe the unusual clustering of circumscribed juvenile PRP cases in our
      pediatric dermatology clinic in 2011. A retrospective chart review was done of
      patients presenting during the summer of 2011 with classic findings of
      circumscribed juvenile PRP. Clinical data including past medical and family
      history, presenting symptoms, infectious disease history and evaluation, biopsy
      results, and management were recorded. Seven patients, ages 5 to 19 years, all
      had strikingly similar skin findings of pink to hyperpigmented, well-defined,
      scaly papules and plaques on their elbows, knees, dorsal hands, ankles, and
      Achilles tendons. Four of the seven also had palmoplantar involvement. Four were
      sibling pairs and the other three were unrelated. Streptococcus pyogenes
      infection was suspected as a trigger in four of the patients. The unusual
      clustering of this uncommon disease, along with the occurrence in two sibling
      pairs, suggests that a genetic susceptibility unmasked by an infectious agent may
      play a role in its pathogenesis. 

PMID- 24456131
TI  - Kidney transplantation outcomes from expanded criteria donors, standard criteria
      donors or living donors older than 60 years.
AB  - OBJECTIVES: To evaluate outcomes in kidney allograft recipients from donors with
      expanded criteria (ECD) versus standard criteria (SCD) or living donors (LD) >60
      years. METHODS: We studied all patients who received a kidney between 2005 and
      2011, focusing in recipients of kidneys from deceased ECD, SCD and LD >60 years.
      ECD was any deceased donor >60 years or >50 years with two of the following:
      hypertension (HTN), stroke as the cause of death, or serum creatinine >1.5 mg/dL.
      We recorded characteristics of the transplant procedure, patient, graft survival
      and renal function 1 year after transplantation and at the end of follow-up.
      RESULTS: Six-hundred and five patients were transplanted between 2005 and 2011 in
      our department. There were 142 (25.1%) transplantations from ECD, 192 (33.98%)
      from SCD and 96 (16.99%) from LDs older than 60 years. In a mean follow-up time
      of 36.4 months, graft survival rates were similar for all groups. Calculated GFR
      was found statistically different between the ECD and SCD groups, but still
      satisfactory at first year, and at end of follow-up time. Comparison of the
      patients, who received transplants from ECD, even older than 70 years, and those
      from LD >60 years revealed equivalent renal function in short and long term.
      CONCLUSIONS: Utilization of marginal kidneys effectively doubled our deceased
      transplant volume in the period 2005-2011. Patients' and graft survival were
      shown similar at the end of follow-up for all groups. Renal outcomes were shown
      equivalent between the ECD and LD >60 years groups, and although significantly
      lower between the ECD and the SCD group, were still very satisfactory.

PMID- 24456132
TI  - Gamma interferon production and plasma concentrations of pregnancy-associated
      glycoproteins 1 and 2 in gestating dairy cows naturally infected with Neospora
      caninum.
AB  - Gamma interferon (IFN-gamma) production and cross-breed pregnancy have been
      attributed a role in protecting dairy cows infected with Neospora caninum against
      abortion. Plasma levels of pregnancy-associated glycoproteins-1 (PAG-1) are a
      marker of placental/foetal well-being and of PAG-2 is an abortion risk indicator
      in chronically N. caninum-infected animals. The present study examines, in cross
      breed pregnancies, interactions between IFN-gamma production and levels of PAG-1
      and PAG-2 in non-aborting naturally Neospora-infected dairy cows. Data were
      obtained from 60 pregnant Holstein-Friesian cows: 44 Neospora-seropositive and 16
      Neospora-seronegative; 12 became pregnant using Holstein-Friesian semen and 48
      using Limousin semen. Blood samples were collected on Days 40, 90, 120, 150, 180
      and 210 of gestation. Gamma interferon was only detected in the plasma of nine of
      the 44 Neospora-seropositive cows, all of them became pregnant using Limousin
      semen. Through GLM procedures, in cows inseminated with Limousin semen and
      Neospora-seropositive cows showing no IFN-gamma production, PAG-1 concentrations
      were high and increased throughout gestation compared to the levels detected in
      cows inseminated with Holstein-Friesian semen and Neospora-seropositive cows
      producing IFN-gamma, respectively. In Neospora-seronegative cows and in Neospora
      seropositive cows showing no IFN-gamma production, significantly increased PAG-2
      concentrations were observed on gestation Day 120. Our findings indicate that IFN
      gamma production correlates negatively and the production of antibodies against
      N. caninum is uncorrelated with plasma PAG concentrations during gestation in
      Neospora-infected dairy cows. Accordingly, IFN-gamma production could be linked
      to the transplacental migration of tachyzoites, which may cause a reduction in
      PAG levels. 

PMID- 24456133
TI  - Would legalizing illicit opioids reduce overdose fatalities? Implications from a
      natural experiment.
AB  - Overdose is the leading cause of premature mortality among heroin users. We
      examine whether the provision of regulated and quality-controlled heroin to users
      in specified doses would reduce heroin overdose rates. We also address this in
      the context of the epidemic of prescription opioid use and deaths seen in recent
      years in the United States and internationally. We explore the extent to which
      any change in legal access to heroin would affect overdose rates, and note that
      this depends upon the validity of the two main assumptions that variations in
      illicit drug purity and/or the presence of drug contaminants are major causes of
      overdose. Toxicological and demographic data from studies of heroin overdose
      deaths do not support these assumptions. The surge in the use of pharmaceutical
      opioids provides an example of the legal delivery of opioids of known dosage and
      free of contaminants, where overdose deaths can be examined to test these
      assumptions. Rates of fatal opioid overdose have escalated, with increased rates
      of prescribing of pharmaceutical opioids. On the basis of the experience with
      prescription opioids, unregulated legal heroin access would not reduce overdose
      rates. 

PMID- 24456134
TI  - A new microporous zeolitic silicoborate (ITQ-52) with interconnected small and
      medium pores.
AB  - A new zeolite (named as ITQ-52) having large cavities and small and medium
      channels has been synthesized. This was achieved by using a new family of amino
      phosphonium cations as organic structure directing agents (OSDA). These cations
      contain P-C and P-N bonds, and therefore they lie between previously reported P
      containing OSDA, such as tetraalkylphosphonium and phosphazenes. In this study,
      it has been found that 1,4-butanediylbis[tris(dimethylamino)]phosphonium dication
      is a very efficient OSDA for crystallization of several zeolites, and in some
      particular conditions, the new zeolite ITQ-52 was synthesized as a pure phase.
      The structure of ITQ-52 has been solved using high-resolution synchrotron X-ray
      powder diffraction data of the calcined solid. This new zeolite crystallizes in
      the space group I2/m, with cell parameters a = 17.511 A, b = 17.907 A, c = 12.367
      A, and beta = 90.22 degrees . The topology of ITQ-52 can be described as a
      replication of a composite building unit with ring notation [4(3)5(4)6(1)] that
      gives rise to the formation of an interconnected 8R and 10R channel system. 

PMID- 24456135
TI  - How solvent influences the anomeric effect: roles of hyperconjugative versus
      steric interactions on the conformational preference.
AB  - The block-localized wave function (BLW) method, which can derive optimal electron
      localized state with intramolecular electron delocalization completely
      deactivated, has been combined with the polarizable continuum model (PCM) to
      probe the variation of the anomeric effect in solution. Currently both the
      hyperconjugation and electrostatic models have been called to interpret the
      anomeric effect in carbohydrate molecules. Here we employed the BLW-PCM scheme to
      analyze the energy differences between alpha and beta anomers of substituted
      tetrahydropyran C5OH9Y (Y = F, Cl, OH, NH2, and CH3) and tetrahydrothiopyran
      C5SH9Y (Y = F, Cl, OH, and CH3) in solvents including chloroform, acetone, and
      water. In accord with literature, our computations show that for anomeric systems
      the conformational preference is reduced in solution and the magnitude of
      reduction increases as the solvent polarity increases. Significantly, on one hand
      the solute-solvent interaction diminishes the intramolecular electron
      delocalization in beta anomers more than in alpha anomers, thus destabilizing
      beta anomers relatively. But on the other hand, it reduces the steric effect in
      beta anomers much more than alpha anomers and thus stabilizes beta anomers
      relatively more, leading to the overall reduction of the anomeric effect in
      anomeric systems in solutions. 

PMID- 24456137
TI  - Resolution of methotrexate-induced Epstein-Barr virus-associated mucocutaneous
      ulcer.

PMID- 24456138
TI  - Rice MtN3/saliva/SWEET gene family: Evolution, expression profiling, and sugar
      transport.
AB  - The rice MtN3/saliva/SWEET gene family consists of 21 paralogs. However, their
      functions in physiological processes are largely unknown, although at least three
      of the 21 paralogs are used by pathogenic bacteria to infect rice. Here, we
      report the evolutionary features, transcriptional characteristics, and putative
      functions in sugar transport of this gene family. The wild rice accessions in
      this study included those with AA, BB, CC, BBCC, CCDD, EE, and GG genomes, which
      appeared approximately 0.58-14.6 million years ago. The structures, chromosomal
      locations, phylogenetic relationships, and homologous distribution among the
      accessions suggest that the number of rice MtN3/saliva/SWEET paralogs gradually
      increased as the Oryza genus evolved, and one third of the paralogs may have
      originated recently. These paralogs are differentially expressed in vegetative
      and reproductive tissues, in the leaf senescence process, and in signaling
      dependent on gibberellic acid, cytokinin, or 1-naphthalene acetic acid (an analog
      of auxin), suggesting that they may be associated with multiple physiological
      processes. Four paralogs could transport galactose in yeast, which suggests that
      they may have a similar function in rice. These results will help to elucidate
      their roles and biochemical functions in rice development, adaptation to
      environment, host-pathogen interaction, and so forth. 

PMID- 24456140
TI  - Phosphorylation and membrane association of the Rubella virus capsid protein is
      important for its anti-apoptotic function.
AB  - Rubella virus (RV), a member of Togaviridae, is an important human pathogen that
      can cause severe defects in the developing fetus. Compared to other togaviruses,
      RV replicates very slowly suggesting that it must employ effective mechanisms to
      delay the innate immune response. A recent study by our laboratory revealed that
      the capsid protein of RV is a potent inhibitor of apoptosis. A primary mechanism
      by which RV capsid interferes with programmed cell death appears to be through
      interaction with the pro-apoptotic Bcl-2 family member Bax. In the present study,
      we report that the capsid protein also blocks IRF3-dependent apoptosis induced by
      the double-strand RNA mimic polyinosinic-polycytidylic acid. In addition,
      analyses of cis-acting elements revealed that phosphorylation and membrane
      association are important for its anti-apoptotic function. Finally, the
      observation that hypo-phosphorylated capsid binds Bax just as well as wild-type
      capsid protein suggests that interaction with this pro-apoptotic host protein in
      and of itself is not sufficient to block programmed cell death. This provides
      additional evidence that this viral protein inhibits apoptosis through multiple
      mechanisms.

PMID- 24456141
TI  - The complete mitochondrial genome sequence of the Tibetan red fox (Vulpes vulpes
      montana).
AB  - In this study, the complete mitochondrial genome of the Tibetan red fox (Vulpes
      Vulpes montana) was sequenced for the first time using blood samples obtained
      from a wild female red fox captured from Lhasa in Tibet, China. Qinghai--Tibet
      Plateau is the highest plateau in the world with an average elevation above 3500
      m. Sequence analysis showed it contains 12S rRNA gene, 16S rRNA gene, 22 tRNA
      genes, 13 protein-coding genes and 1 control region (CR). The variable tandem
      repeats in CR is the main reason of the length variability of mitochondrial
      genome among canide animals.

PMID- 24456142
TI  - Resveratrol appears to protect against oxidative stress and steroidogenesis
      collapse in mice fed high-calorie and high-cholesterol diet.
AB  - The detrimental effects on Leydig cells steroidogenesis in mice on high-calorie
      and high-cholesterol diet (HCD) were determined, and the possible protection
      conferred by resveratrol supplementation was investigated. Male C57BL/6J mice
      were fed high-calorie and alone (HCD group) or with resveratrol supplementation
      (HCD + Res group) for 18 weeks. Male C57BL/6J mice fed standard diet without or
      with the same dose of resveratrol served as controls. At the end of the
      experiment, there were significant declines of serum testosterone and luteinising
      hormone (LH) in HCD group as compared to controls. In line with the hormone
      alterations, the expressions of StAR and steroidogenic enzymes in testicular
      tissues were significantly down-regulated in HCD group. Resveratrol
      supplementation could significantly improve expressions of StAR and steroidogenic
      enzymes, and increase serum testosterone and LH concentrations in HCD + Res
      group. Mice in HCD group also showed a statistically significant down-regulation
      in the mRNA expressions of MnSOD and GPx4. Resveratrol supplementation improved
      testicular MnSOD and GPx4 expression in comparison with HCD group. We propose
      that resveratrol may attenuate detrimental effects on Leydig cells
      steroidogenesis in HCD-fed mice, and its upregulations of antioxidant defence
      mechanisms and LH level may play a role in its protection. Our data suggest
      resveratrol appears to have the potential for therapeutic approaches targeting
      male obesity-associated secondary hypogonadism.

PMID- 24456136
TI  - The ESCRT machinery: from the plasma membrane to endosomes and back again.
AB  - The manipulation and reorganization of lipid bilayers are required for diverse
      cellular processes, ranging from organelle biogenesis to cytokinetic abscission,
      and often involves transient membrane disruption. A set of membrane-associated
      proteins collectively known as the endosomal sorting complex required for
      transport (ESCRT) machinery has been implicated in membrane scission steps, which
      transform a single, continuous bilayer into two distinct bilayers, while
      simultaneously segregating cargo throughout the process. Components of the ESCRT
      pathway, which include 5 distinct protein complexes and an array of accessory
      factors, each serve discrete functions. This review focuses on the molecular
      mechanisms by which the ESCRT proteins facilitate cargo sequestration and
      membrane remodeling and highlights their unique roles in cellular homeostasis.

PMID- 24456143
TI  - Effects of pre- or post-exercise low-level laser therapy (830 nm) on skeletal
      muscle fatigue and biochemical markers of recovery in humans: double-blind
      placebo-controlled trial.
AB  - OBJECTIVES: The purpose of this study was to investigate the effect of low-level
      laser therapy (LLLT) before and after exercise on quadriceps muscle performance,
      and to evaluate the changes in serum lactate and creatine kinase (CK) levels.
      METHODS: The study was randomized, double blind, and placebo controlled.
      PATIENTS: A sample of 27 healthy volunteers (male soccer players) were divided
      into three groups: placebo, pre-fatigue laser, and post-fatigue laser. The
      experiment was performed in two sessions, with a 1 week interval between them.
      Subjects performed two sessions of stretching followed by blood collection
      (measurement of lactate and CK) at baseline and after fatigue of the quadriceps
      by leg extension. LLLT was applied to the femoral quadriceps muscle using an
      infrared laser device (830 nm), 0.0028 cm(2) beam area, six 60 mW diodes, energy
      of 0.6 J per diode (total energy to each limb 25.2 J (50.4 J total), energy
      density 214.28 J/cm(2), 21.42 W/cm(2) power density, 70 sec per leg. We measured
      the time to fatigue and number and maximum load (RM) of repetitions tolerated.
      Number of repetitions and time until fatigue were primary outcomes, secondary
      outcomes included serum lactate levels (measured before and 5, 10, and 15 min
      after exercise), and CK levels (measured before and 5 min after exercise).
      RESULTS: The number of repetitions (p=0.8965), RM (p=0.9915), and duration of
      fatigue (p=0.8424) were similar among the groups. Post-fatigue laser treatment
      significantly decreased the serum lactate concentration relative to placebo
      treatment (p<0.01) and also within the group over time (after 5 min vs. after 10
      and 15 min, p<0.05 both). The CK level was lower in the post-fatigue laser group
      (p<0.01). CONCLUSIONS: Laser application either before or after fatigue reduced
      the post-fatigue concentrations of serum lactate and CK. The results were more
      pronounced in the post-fatigue laser group.

PMID- 24456144
TI  - Microbiota and their role in the pathogenesis of oral mucositis.
AB  - Oral mucositis in patients undergoing cancer therapy is a significant problem.
      Its prevalence ranges between 20 and 100%, depending on treatment type and
      protocols and patient-based variables. Mucositis is self-limiting when
      uncomplicated by infection. Unfortunately, the incidence of developing a local or
      systemic infection during the course of the treatment is very high. At this
      stage, it is unclear which role oral microbiota play in the onset, duration, and
      severity of oral mucositis. Nevertheless, there is growing interest in this
      underexplored topic, and new studies are being undertaken to unravel their impact
      on the pathogenesis of mucositis. 

PMID- 24456145
TI  - Preperimetric normal tension glaucoma study: long-term clinical course and effect
      of therapeutic lowering of intraocular pressure.
AB  - PURPOSE: The purpose of this study was to investigate the long-term clinical
      course of normotensive preperimetric glaucoma (PPG). METHODS: The medical records
      of 71 eyes of 71 patients with normotensive PPG who underwent intraocular
      pressure (IOP)-lowering therapy were reviewed retrospectively. The patients had
      been regularly followed up at 3- to 6-month intervals between 1996 and 2011.
      Progression was evaluated by comparing the structural changes of serial
      stereoscopic colour disc and red-free retinal nerve fibre layer (RNFL)
      photographs and by comparing serial visual field (VF) test results for functional
      changes. RESULTS: Over an average follow-up period of 6.8 years, 41 eyes (57.7%)
      showed progression in either structural or functional evaluation. Disc
      haemorrhage (DH) was observed significantly more frequently in the progressing
      group (p < 0.005); however, there were no differences in mean age, gender ratio,
      follow-up period and ocular characteristics at baseline such as IOP, RNFL defects
      and global indices of VF between the non-progressing and progressing groups.
      Thirty eyes (42.3%) showed significant angular widening of the localized RNFL
      defect towards the macula at a mean rate of approximately 1 degrees /year.
      Perimetric glaucoma developed in 19 eyes (26.8%), and the rate of change in the
      mean deviation was -0.23 dB/year. Preperimetric glaucoma patients with DH or IOP
      reductions of <20% from the baseline had a higher probability of RNFL
      deterioration than patients without DH or IOP reductions of >=20% from the
      baseline by multivariate analysis. CONCLUSION: Although the rates of change were
      typically slow, more than half of normotensive patients with PPG showed
      statistically significant progressive structural or functional changes in
      medically treated cases. DH or IOP reductions of <20% from the baseline were
      shown as a significant risk factor for the progression of PPG.

PMID- 24456146
TI  - Metallodrugs in medicinal inorganic chemistry.

PMID- 24456151
TI  - Humidity-sensing properties of urchinlike CuO nanostructures modified by reduced
      graphene oxide.
AB  - Urchinlike CuO modified by reduced graphene oxide (rGO) was synthesized by a one
      pot microwave-assisted hydrothermal method. The as-prepared composites were
      characterized using various characterization methods. A humidity sensor based on
      the CuO/rGO composites was fabricated and tested. The results revealed that the
      sensor based on the composites showed much higher impedance than pure CuO.
      Compared with the sensors based on pristine rGO and CuO, the sensor fabricated
      with the composites exhibited relatively good humidity-sensing performance in
      terms of response time and response value. The humidity-sensing mechanism was
      also briefly introduced. The enlargement of the impedance and improvement of the
      humidity-sensing properties are briefly explained by the Schottky junction
      theory. 

PMID- 24456150
TI  - A coordinate-based ALE functional MRI meta-analysis of brain activation during
      verbal fluency tasks in healthy control subjects.
AB  - BACKGROUND: The processing of verbal fluency tasks relies on the coordinated
      activity of a number of brain areas, particularly in the frontal and temporal
      lobes of the left hemisphere. Recent studies using functional magnetic resonance
      imaging (fMRI) to study the neural networks subserving verbal fluency functions
      have yielded divergent results especially with respect to a parcellation of the
      inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a
      coordinate-based activation likelihood estimation (ALE) meta-analysis on brain
      activation during the processing of phonemic and semantic verbal fluency tasks
      involving 28 individual studies with 490 healthy volunteers. RESULTS: For
      phonemic as well as for semantic verbal fluency, the most prominent clusters of
      brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG)
      and the anterior cingulate gyrus. BA 44 was only involved in the processing of
      phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and
      semantic fluency tasks. CONCLUSIONS: Our comparison of brain activation during
      the execution of either phonemic or semantic verbal fluency tasks revealed
      evidence for spatially different activation in BA 44, but not other regions of
      the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency
      processing.

PMID- 24456152
TI  - Influence of geriatric oncology consultation on the management of breast cancer
      in older women: a French population-based study.
AB  - AIM: The objective of the present population-based study was to assess the impact
      of geriatric oncology consultation on the management of elderly patients with
      breast cancer and to identify the predictive factors of breast cancer treatment
      in this population. METHODS: A total of 206 women aged 75 years and older with
      breast cancer, diagnosed from January 2007 to December 2009 were included. The
      independent impact of geriatric oncology consultation on treatment was analyzed
      using multivariate logistic regression with adjustment for the other predictive
      factors of treatment. RESULTS: Patients who had a geriatric oncology consultation
      (19.4%) had more comorbidities (Charlson Comorbidity Index >= 1; P = 0.02), more
      advanced tumors (P = 0.025), more aggressive tumors (P = 0.029), were more likely
      to receive mastectomy and adjuvant therapy (P < 0.0001); and less likely to be
      treated by breast-conserving surgery and adjuvant therapy (P = 0.003). Regarding
      the geriatric oncology database, 36 of the 40 patients consulted a geriatrician
      about oncological treatment, and 27 of these 36 patients received the treatment
      suggested by the geriatrician. For the whole population, geriatric oncology
      consultation remained a positive predictor for mastectomy and adjuvant therapy
      (odds ratio 2.32, P = 0.043), and a negative predictor for breast-conserving
      surgery and adjuvant therapy (odds ratio 0.38, P = 0.048). CONCLUSIONS: In the
      present study, we found that treatment of patients who underwent a geriatric
      oncology consultation generally followed the geriatricians' recommendations. The
      geriatric oncology consultation was a positive predictor of mastectomy and
      adjuvant therapy, and a negative predictor of breast-conserving surgery and
      adjuvant therapy.

PMID- 24456153
TI  - Urinary biomarkers in assessing the nephrotoxic potential of gentamicin in
      solitary kidney patients after 7 days of therapy.
AB  - INTRODUCTION: The solitary kidney (SK) may present increased vulnerability to
      nephrotoxicity because of adaptive phenomena. AIMS: Assessing the vulnerability
      of the SK with urinary tract infections (UTI) to gentamicin by means of urinary
      biomarkers (N-acetyl-beta-D-glucosaminidase (NAG) and urinary alpha-1
      microglobulin), as well as glomerular filtration rate (GFR). METHODS: We studied
      14 patients with SK with UTI (group A) (mean age 58.07 +/- 13.61 years, mean
      duration of SK 13.55 +/- 12.33 years) who were administered gentamicin for 7
      days. Group B consisted by 17 patients with SK without any other associated renal
      pathology (average age 51.17 +/- 9.39 years, average existence period of a single
      kidney 33.23 +/- 21.73 years). We also included a third group (group C)
      represented by nine healthy individuals, with two kidneys. RESULTS: Increased
      values of urinary NAG were found in group B as compared to group C and alpha-1
      microglobulin in group A as compared to group B. During treatment with
      gentamicin, increased values of both NAG and alpha-1-microglobulin in group A
      were found on day 7 as compared to values before treatment (day 7 NAG=18.99 +/-
      14.07 U/g creat versus day 0, NAG=5.15 +/- 6.54 U/g creat, p=0.004; day 7 alpha-1
      microglobulin=20.88 +/- 18.84 mg/g creat versus day 0, urinary alpha-1
      microglobulin=4.96 +/- 6.57 mg/g creat, p=0.003). No statistically significant
      alterations of GFR were noticed after 7 days of treatment. CONCLUSIONS: We found
      the nephrotoxic effects of gentamicin at tubular level, but not at glomerular
      level. The nephrotoxic potential of gentamicin in patients with a SK can be
      monitored by assessing urinary biomarkers during treatment of UTI.

PMID- 24456154
TI  - Use of equine chorionic gonadotropin to control reproduction of the dairy cow: a
      review.
AB  - Equine chorionic gonadotropin (eCG) is a member of the glycoprotein family of
      hormones along with LH, FSH and thyroid-stimulating hormone. In non-equid
      species, eCG shows high LH- and FSH-like activities and has a high affinity for
      both FSH and LH receptors in the ovaries. On the granulosa and thecal cells of
      the follicle, eCG has long-lasting LH- and FSH-like effects that stimulate
      oestradiol and progesterone secretion. Thus, eCG administration in dairy cattle
      results in fewer atretic follicles, the recruitment of more small follicles
      showing an elevated growth rate, the sustained growth of medium and large
      follicles and improved development of the dominant and pre-ovulatory follicle. In
      consequence, the quality of the ensuing CL is improved, and thereby progesterone
      secretion increased. Based on these characteristics, eCG treatment is utilized in
      veterinary medicine to control the reproductive activity of the cow by i)
      improving reproductive performance during early post-partum stages; ii)
      increasing ovulation and pregnancy rates in non-cyclic cows; iii) improving the
      conception rate in cows showing delayed ovulation; and finally, iv) eCG is
      currently included in protocols for fixed-time artificial insemination since
      after inducing the synchrony of ovulation using a progesterone-releasing device,
      eCG has beneficial effects on embryo development and survival. The above effects
      are not always observed in cyclic animals, but they are evident in animals in
      which LH secretion and ovarian activity are reduced or compromised, for instance,
      during the early post-partum period, under seasonal heat stress, in anoestrus
      animals or in animals with a low body condition score. 

PMID- 24456155
TI  - An international consensus for assessing internet gaming disorder using the new
      DSM-5 approach.
AB  - AIMS: For the first time, the Diagnostic and Statistical Manual for Mental
      Disorders (DSM-5) introduces non-substance addictions as psychiatric diagnoses.
      The aims of this paper are to (i) present the main controversies surrounding the
      decision to include internet gaming disorder, but not internet addiction more
      globally, as a non-substance addiction in the research appendix of the DSM-5, and
      (ii) discuss the meaning behind the DSM-5 criteria for internet gaming disorder.
      The paper also proposes a common method for assessing internet gaming disorder.
      Although the need for common diagnostic criteria is not debated, the existence of
      multiple instruments reflect the divergence of opinions in the field regarding
      how best to diagnose this condition. METHODS: We convened international experts
      from European, North and South American, Asian and Australasian countries to
      discuss and achieve consensus about assessing internet gaming disorder as defined
      within DSM-5. RESULTS: We describe the intended meaning behind each of the nine
      DSM-5 criteria for internet gaming disorder and present a single item that best
      reflects each criterion, translated into the 10 main languages of countries in
      which research on this condition has been conducted. CONCLUSIONS: Using results
      from this cross-cultural collaboration, we outline important research directions
      for understanding and assessing internet gaming disorder. As this field moves
      forward, it is critical that researchers and clinicians around the world begin to
      apply a common methodology; this report is the first to achieve an international
      consensus related to the assessment of internet gaming disorder.

PMID- 24456157
TI  - Two cases of lichen striatus with prolonged active phase.
AB  - Lichen striatus is a localized, eczematous disorder distributed along the lines
      of Blaschko, primarily affecting children. In the literature, lesions have been
      described as having an active phase of inflamed lesions for 6 to 12 months
      followed by flattening and persistent pigmentary alteration. We describe two
      girls who had prolonged active-phase lesions for 2.5 and 3.5 years, respectively.
      Practitioners should be aware that lesions of lichen striatus may have a
      prolonged active phase.

PMID- 24456156
TI  - Bisulfite and sulfite as derivatives of sulfur dioxide alters biomechanical
      behaviors of airway smooth muscle cells in culture.
AB  - Sulfur dioxide (SO2) is a common air pollutant that triggers asthmatic symptoms,
      but its toxicological mechanisms are not fully understood. Specifically, it is
      unclear how SO2 in vivo affects airway smooth muscle (ASM) cells of which the
      mechanics is known to ultimately mediate airway hyperresponsiveness (AHR) - a
      hallmark feature of asthma. To this end, we investigated the effects of
      bisulfite/sulfite (1:3 M/M in neutral fluid to simulate the in vivo derivatives
      of inhaled SO2 in the airways), on the viability, migration, stiffness and
      contractility of ASM cells cultured in vitro. The results showed that
      bisulfite/sulfite consistently increased viability, migration, F-actin intensity
      and stiffness of ASM cells in similar fashion as concentration increasing from
      10(-4) to 10(-1) mmol/L. However, bisulfite/sulfite increased the ASM cell
      contractility induced by KCl only at the concentration between 10(-4) and 10(-3)
      mmol/L (p < 0.05), while having no consistent effect on that induced by
      histamine. At the concentration of 10(0) mmol/L, bisulfite/sulfite became acutely
      toxic to the ASM cells. Taken together, the data suggest that SO2 derivatives at
      low levels in vivo may directly increase the mass, stiffness and contractility of
      ASM cells, which may help understand the mechanism in which specific air
      pollutants contribute in vivo to the pathogenesis of asthma.

PMID- 24456158
TI  - Editorial: looking forward to another successful year.

PMID- 24456159
TI  - Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are
      associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome.
AB  - Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized
      by polysyndactyly of hands and/or feet, mirror image duplication of the feet,
      nasal defects, and loss of identity between fibula and tibia. The genetic basis
      of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type
      polysyndactyly (HTS) regarding the digital phenotype. Here we report on five
      unrelated families with overlapping microduplications encompassing the Sonic
      hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36.
      Clinically, the patients show polysyndactyly phenotypes and various types of
      lower limb malformations ranging from syndactyly to mirror image polydactyly with
      duplications of the fibulae. We show that larger duplications of the ZRS region
      (>80 kb) are associated with HTS, whereas smaller duplications (<80 kb) result in
      the LSS phenotype. On the basis of our data, the latter can be clearly
      distinguished from HTS by the presence of mirror image polysyndactyly of the feet
      with duplication of the fibula. Our results expand the clinical phenotype of the
      ZRS-associated syndromes and suggest that smaller duplications (<80 kb) are
      associated with a more severe phenotype. In addition, we show that these small
      microduplications within the ZRS region are the underlying genetic cause of
      Laurin-Sandrow syndrome.

PMID- 24456160
TI  - Acceleration of an aromatic Claisen rearrangement via a designed spiroligozyme
      catalyst that mimics the ketosteroid isomerase catalytic dyad.
AB  - A series of hydrogen-bonding catalysts have been designed for the aromatic
      Claisen rearrangement of a 1,1-dimethylallyl coumarin. These catalysts were
      designed as mimics of the two-point hydrogen-bonding interaction present in
      ketosteroid isomerase that has been proposed to stabilize a developing negative
      charge on the ether oxygen in the migration of the double bond.1 Two hydrogen
      bond donating groups, a phenol alcohol and a carboxylic acid, were grafted onto a
      conformationally restrained spirocyclic scaffold, and together they enhance the
      rate of the Claisen rearrangement by a factor of 58 over the background reaction.
      Theoretical calculations correctly predict the most active catalyst and suggest
      that both preorganization and favorable interactions with the transition state of
      the reaction are responsible for the observed rate enhancement. 

PMID- 24456161
TI  - Manganese-mediated C3-selective direct alkylation and arylation of 2-pyridones
      with diethyl malonates and arylboronic acids.
AB  - A manganese-mediated dehydrogenative direct alkylation of 2-pyridones with
      diethyl malonates has been developed. A similar reaction system is applicable to
      the direct arylation with arylboronic acids. These manganese-based reactions
      occur regioselectively at the C3 position of the 2-pyridones. The observed high
      C3 regioselectivity can complement precedented C-H functionalization protocols of
      the 2-pyridones in view of the site selectivity. 

PMID- 24456162
TI  - A serum component mediates food restriction-induced growth attenuation.
AB  - Proper nutrition in terms of calories and essential food components is required
      to maximize longitudinal growth in children. Our previous study showed that
      prepubertal male rats subjected to 10 days of 40% food restriction (RES)
      exhibited a dramatic reduction in weight and epiphyseal growth plate height, as
      well as changes in gene expression and microRNAs (miRNAs) in the epiphyseal
      growth plate. These findings reversed rapidly after renewal of the regular food
      supply (catch-up [CU]). To further elucidate the mechanisms underlying the
      nutrition-growth association, serum collected from the RES and CU rats and
      control rats fed ad libitum (AL) was added to the culture medium of the
      chondrocyte cell line ATDC5 (instead of fetal calf serum). Serum from the RES
      group induced a reduction in cell viability (25%, P < .05) concomitant with an
      increase in cell differentiation compared with that for the AL group serum. The
      most interesting observation, in our opinion, was the significant reduction in
      the expression of specific miRNAs, including the chondro-specific miR-140. These
      effects were not observed for serum from refed (CU) rats. Serum levels of IGF-I,
      leptin, and fibroblast growth factor 21 were reduced by food restriction. The
      addition of IGF-I and leptin to the culture increased cell viability, whereas
      fibroblast growth factor 21 reduced it, suggesting the involvement of IGF-I,
      leptin, and possibly other still unidentified serum factors in chondrocyte cell
      growth. In conclusion, specific miRNAs respond to nutritional cues, and these
      effects are mediated by serum-borne factors. These results may promote the
      development of superior interventions for children with malnutrition and growth
      abnormalities. 

PMID- 24456164
TI  - Prolactin regulates kisspeptin neurons in the arcuate nucleus to suppress LH
      secretion in female rats.
AB  - Prolactin (PRL) is known to suppress LH secretion. Kisspeptin neurons regulate LH
      secretion and express PRL receptors. We investigated whether PRL acts on
      kisspeptin neurons to suppress LH secretion in lactating (Lac) and virgin rats.
      Lac rats displayed high PRL secretion and reduced plasma LH and kisspeptin
      immunoreactivity in the arcuate nucleus (ARC). Bromocriptine-induced PRL blockade
      significantly increased ARC kisspeptin and plasma LH levels in Lac rats but did
      not restore them to the levels of non-Lac rats. Bromocriptine effects were
      prevented by the coadministration of ovine PRL (oPRL). Virgin ovariectomized
      (OVX) rats treated with either systemic or intracerebroventricular oPRL displayed
      reduction of kisspeptin expression in the ARC and plasma LH levels, and these
      effects were comparable with those of estradiol treatment in OVX rats.
      Conversely, estradiol-treated OVX rats displayed increased kisspeptin
      immunoreactivity in the anteroventral periventricular nucleus, whereas oPRL had
      no effect in this brain area. The expression of phosphorylated signal transducer
      and activator of transcription 5 was used to determine whether kisspeptin neurons
      in the ARC were responsive to PRL. Accordingly, intracerebroventricular oPRL
      induced expression of phosphorylated signal transducer and activator of
      transcription 5 in the great majority of ARC kisspeptin neurons in virgin and Lac
      rats. We provide here evidence that PRL acts on ARC neurons to inhibit kisspeptin
      expression in female rats. During lactation, PRL contributes to the inhibition of
      ARC kisspeptin. In OVX rats, high PRL levels suppress kisspeptin expression and
      reduce LH release. These findings suggest a pathway through which
      hyperprolactinemia may inhibit LH secretion and thereby cause infertility. 

PMID- 24456163
TI  - Pigment epithelium-derived factor (PEDF) suppresses IL-1beta-mediated c-Jun N
      terminal kinase (JNK) activation to improve hepatocyte insulin signaling.
AB  - Pigment epithelium-derived factor (PEDF) is an antiinflammatory protein that
      circulates at high levels in the metabolic syndrome. Metabolic studies of PEDF
      knockout (KO) mice were conducted to investigate the relationship between PEDF,
      inflammatory markers, and metabolic homeostasis. Male PEDF KO mice demonstrated a
      phenotype consisting of increased adiposity, glucose intolerance, and elevated
      serum levels of metabolites associated with the metabolic syndrome. Genome
      expression analysis revealed an increase in IL-1beta signaling in the livers of
      PEDF KO mice that was accompanied by impaired IRS and Akt signaling. In human
      hepatocytes, PEDF blocked the effects of an IL-1beta challenge by suppressing
      activation of the inflammatory mediator c-Jun N-terminal kinase while restoring
      Akt signaling. RNA interference of PEDF in human hepatocytes was permissive for c
      Jun N-terminal kinase activation and decreased Akt signaling. A metabolomics
      profile identified elevated circulating levels of tricarboxyclic acid cycle
      intermediates including succinate, an inducer of IL-1beta, in PEDF KO mice.
      Succinate-dependent IL-1beta expression was blocked by PEDF in PEDF KO, but not
      wild-type hepatocytes. In vivo, PEDF restoration reduced hyperglycemia and
      improved hepatic insulin signaling in PEDF KO mice. These findings identify
      elevated PEDF as a homeostatic mechanism in the human metabolic syndrome. 

PMID- 24456166
TI  - Genetic analysis of biomass and photosynthetic parameters in wheat grown in
      different light intensities.
AB  - Growth light intensities largely determine photosynthesis, biomass, and grain
      yield of cereal crops. To explore the genetic basis of light responses of biomass
      and photosynthetic parameters in wheat (Triticum aestivum L.), a quantitative
      trait locus (QTL) analysis was carried out in a doubled haploid (DH) population
      grown in low light (LL), medium light (ML), and high light (HL), respectively.
      The results showed that the wheat seedlings grown in HL produced more biomass
      with lower total chlorophyll content (Chl), carotenoid content, and maximum
      photochemical efficiency of photosystem II (Fv/Fm) while the wheat seedlings
      grown in LL produced less biomass with higher Chl compared with those grown in
      ML. In total, 48 QTLs were identified to be associated with the investigated
      parameters in relation to growth light intensities. These QTLs were mapped to 15
      chromosomes which individually explained 6.3%-36.0% of the phenotypic variance,
      of which chromosomes 3A, 1D, and 6B were specifically involved in LL response, 5D
      and 7A specifically involved in ML response, and 4B specifically involved in HL
      response. Several light-responsive QTLs were co-located with QTLs for
      photosynthetic parameters, biomass, and grain weight under various conditions
      which may provide new hints to uncover the genetic control of photosynthesis,
      biomass, and grain weight. 

PMID- 24456167
TI  - Role of intertube interactions in double- and triple-walled carbon nanotubes.
AB  - Resonant Raman spectroscopy studies are performed to access information about the
      intertube interactions and wall-to-wall distances in double- and triple-walled
      carbon nanotubes. Here, we explain how the surroundings of the nanotubes in a
      multiwalled system influence their radial breathing modes. Of particular
      interest, the innermost tubes in double- and triple-walled carbon nanotube
      systems are shown to be significantly shielded from environmental interactions,
      except for those coming from the intertube interaction with their own respective
      host tubes. From a comparison of the Raman results for bundled as well as
      individual fullerene-peapod-derived double- and triple-walled carbon nanotubes,
      we observe that metallic innermost tubes, when compared to their semiconducting
      counterparts, clearly show weaker intertube interactions. Additionally, we
      discuss a correlation between the wall-to-wall distances and the frequency
      upshifts of the radial breathing modes observed for the innermost tubes in
      individual double- and triple-walled carbon nanotubes. All results allow us to
      contemplate fundamental properties related to DWNTs and TWNTs, as for example
      diameter- and chirality-dependent intertube interactions. We also discuss
      differences in fullerene-peapod-derived and chemical vapor deposition grown
      double- and triple-walled systems with the focus on mechanical coupling and
      interference effects. 

PMID- 24456165
TI  - Administration of saccharin to neonatal mice influences body composition of adult
      males and reduces body weight of females.
AB  - Nutritional or pharmacological perturbations during perinatal growth can cause
      persistent effects on the function of white adipose tissue, altering
      susceptibility to obesity later in life. Previous studies have established that
      saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and
      stimulates adipogenesis. Thus, the current study tested whether neonatal exposure
      to saccharin via maternal lactation increased susceptibility of mice to diet
      induced obesity. Saccharin decreased body weight of female mice beginning
      postnatal week 3. Decreased liver weights on week 14 corroborated this diminished
      body weight. Initially, saccharin also reduced male mouse body weight. By week 5,
      weights transiently rebounded above controls, and by week 14, male body weights
      did not differ. Body composition analysis revealed that saccharin increased lean
      and decreased fat mass of male mice, the latter due to decreased adipocyte size
      and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose
      tolerance without a change in insulin sensitivity or secretion aligned with this
      leaner phenotype. Interestingly, microcomputed tomography analysis indicated that
      saccharin also increased cortical and trabecular bone mass of male mice and
      modified cortical bone alone in female mice. A modest increase in circulating
      testosterone may contribute to the leaner phenotype in male mice. Accordingly,
      the current study established a developmental period in which saccharin at high
      concentrations reduces adiposity and increases lean and bone mass in male mice
      while decreasing generalized growth in female mice. 

PMID- 24456168
TI  - Diagnostic accuracy of the faecal immunochemical test for colorectal cancer in
      symptomatic patients: comparison with NICE and SIGN referral criteria.
AB  - AIM: The diagnostic accuracy of the faecal immunochemical test (FIT) at a 100
      ng/ml threshold for colorectal cancer (CRC) was compared with National Institute
      for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines
      Network (SIGN) referral criteria. METHOD: A multicentre, prospective, blind study
      of diagnostic tests was carried out in two Spanish health areas. In 787
      symptomatic patients referred for a diagnostic colonoscopy, we determined whether
      patients met NICE and SIGN referral criteria. All patients performed one FIT
      determination (OCsensor(TM) ). The sensitivity and specificity for CRC detection
      were determined with McNemar's test. The diagnostic odds ratio as well as the
      number needed to scope (NNS) to detect a CRC were calculated. RESULTS: We
      detected CRC in 97 (12.3%) patients; 241 (30.6%) had an FIT >= 100 ng/ml and 300
      (38.1%) and 473 (60.1%) met NICE and SIGN referral criteria. The FIT had a higher
      sensitivity for CRC detection than NICE criteria (87.6%, 61.9%; P < 0.001) and
      SIGN criteria (82.5%; P = 0.4). The specificity of FIT was also higher than NICE
      and SIGN criteria (77.4%, 65.2%, 42.7%; P < 0.001). The odds ratios of FIT, NICE
      and SIGN criteria for the diagnosis of CRC were 24.24 (95% CI 12.91-45.53), 3.04
      (95% CI 1.96-4.71) and 3.51 (95% CI 2.03-6.06). The NNS to detect a CRC in
      individuals with an FIT >= 100 ng/ml was 2.83 (95% CI 2.4-3.41) and in
      individuals who met NICE and SIGN criteria it was 5 (95% CI 3.98-6.37) and 5.95
      (95% CI 4.85-7.35). CONCLUSION: Our study suggests that FIT is more accurate for
      the detection of CRC than the current NICE and SIGN referral criteria in
      symptomatic patients referred for colonoscopy.

PMID- 24456170
TI  - Effect of photon-initiated photoacoustic streaming on removal of apically placed
      dentinal debris.
AB  - AIM: To compare the efficacy of photon-induced photoacoustic streaming (PIPS)
      technique with conventional, sonic and ultrasonic irrigation on the removal of
      apically placed dentinal debris from an artificial groove created in a root
      canal. METHODOLOGY: Root canal preparation was performed up to size 40 on 48
      extracted single-rooted teeth using ProTaper rotary instruments. The specimens
      were then split longitudinally, and a standardized groove was prepared in the
      apical part of each segment. Each groove was filled with dentinal debris mixed
      with 5% NaOCl. Each tooth was reassembled and irrigated as follows: (i)
      conventional irrigation with 1% NaOCl, (ii) sonic, (iii) ultrasonic irrigation,
      and (iv) PIPS. The root segments were disassembled, and the amount of remaining
      dentinal debris was evaluated under a stereomicroscope at 20* magnification,
      using a four-grade scoring system. The data were evaluated statistically using
      Kruskal-Wallis and Mann-Whitney U-tests with a 95% confidence level (P = 0.05).
      RESULTS: Photon-induced photoacoustic streaming removed significantly more
      dentinal debris than conventional irrigation (P < 0.001), sonic irrigation (P <
      0.001) or ultrasonic irrigation (P = 0.005). There was no significant difference
      between sonic and ultrasonic irrigation (P = 0.377). CONCLUSIONS: Photon-induced
      photoacoustic streaming was more effective than conventional, sonic and
      ultrasonic irrigation in the removal of apically placed dentinal debris.

PMID- 24456169
TI  - Derivation of human differential photoreceptor cells from adult human dermal
      fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD.
AB  - Redirecting differentiation of somatic cells by over-expression of transcription
      factors is a promising approach for regenerative medicine, elucidation of
      pathogenesis and development of new therapies. We have previously defined a
      transcription factor combination, that is, CRX, RAX and NEUROD, that can generate
      photosensitive photoreceptor cells from human iris cells. Here, we show that
      human dermal fibroblasts are differentiated to photoreceptor cells by the same
      transcription factor combination as human iris cells. Transduction of a
      combination of the CRX, RAX and NEUROD genes up-regulated expression of the
      photoreceptor-specific genes, recoverin, blue opsin and PDE6C, in all three
      strains of human dermal fibroblasts that were tested. Additional OTX2 gene
      transduction increased up-regulation of the photoreceptor-specific genes blue
      opsin, recoverin, S-antigen, CNGB3 and PDE6C. Global gene expression data by
      microarray analysis further showed that photoreceptor-related functional genes
      were significantly increased in induced photoreceptor cells. Functional analysis,
      that is, patch-clamp recordings, clearly revealed that induced photoreceptor
      cells from fibroblasts responded to light. Both the NRL gene and the NR2E3 gene
      were endogenously up-regulated in induced photoreceptor cells, implying that
      exogenous CRX, RAX, OTX2 and NEUROD, but not NRL, are sufficient to generate rod
      photoreceptor cells. 

PMID- 24456171
TI  - Diagnosis of occlusal caries using laser fluorescence versus conventional methods
      in permanent posterior teeth: a clinical study.
AB  - OBJECTIVE: The purpose of this in vivo study was to compare three different
      caries detection methods [laser fluorescence (LFE), visual examination (VE), and
      radiological examination (RE)] for the detection of occlusal caries in permanent
      posterior teeth. BACKGROUND DATA: Early diagnosis of caries is critical in the
      management of dental caries. METHODS: Two examiners assessed the occlusal
      surfaces of 217 teeth by visual, radiographic, and laser fluorescence (DIAGNOdent
      Pen) examination methods. After a 1 week interval, randomly selected patients
      were recalled. Each measurement was repeated by two examiners before the cases
      were selected for operative intervention to classify lesion depths. Statistical
      analysis of the data was performed using SPSS and Stata IC. The intra- and inter
      examiner reliabilities and reproducibilities of the VE, RE, and LFE were
      calculated using Cohen's kappa statistics. The sensitivities and specificities
      were plotted in receiver operating characteristic curves. The differences between
      LFE scores were analyzed using the nonparametric Mann-Whitney U and Wilcoxon
      tests (alpha=0.05). RESULTS: The VE method exhibited the highest sensitivity,
      accuracy, and kappa values among the diagnostic groups in terms of inter-examiner
      agreement. With regard to the sensitivity, specificity, and likelihood ratios for
      the two examiners, significant differences were found between sensitivity and
      specificity for examiner 1, whereas no statistically significant differences were
      noted between sensitivity and specificity for examiner 2 for the LFE scores.
      CONCLUSIONS: The DIAGNOdent pen is useful for the detection of dentinal caries of
      occlusal surfaces in permanent posterior teeth. Combination with other diagnostic
      conventional methods may enhance the reliability of this tool.

PMID- 24456173
TI  - Visual field loss in optic disc drusen patients correlates with central retinal
      artery blood velocity patterns.
AB  - PURPOSE: (1) To characterize the retrobulbar circulation in patients with optic
      disc drusen (ODD) using colour Doppler imaging; (2) to explore the differences in
      retrobulbar hemodynamics in patients with primary open-angle glaucoma (POAG).
      METHODS: Retrospective analysis using three diagnostic groups: patients with ODD,
      age-matched healthy controls and age- and visual defect-matched patients with
      POAG. Subjects with history of ocular trauma or ocular diseases including
      vascular-related diseases were excluded. Kruskal-Wallis and Spearman's
      correlation tests were performed to compare and explore the correlations between
      the hemodynamic parameters and visual field damage. RESULTS: Sixty patients were
      included and equally divided between the three groups. Patients with ODD had
      lower systolic and diastolic flow velocities in the central retinal artery (CRA)
      when compared to healthy individuals, but no difference was found with the
      glaucoma group (p < 0.005 versus healthy; p range 0.30-0.37 versus POAG). The
      systolic shift in flow patterns correlated with the extent of visual field defect
      in ODD patients (p < 0.001, r = -0.78, confidence interval: -0.43 to -0.92), but
      not in POAG (p = 0.73). Short ciliary arteries from ODD patients had lower mean
      systolic flow velocities when compared to both healthy individuals and patients
      with POAG (p < 0.01 versus healthy; p <= 0.04 versus POAG). The ophthalmic artery
      in ODD group had significantly higher mean blood velocities than in the POAG (p =
      0.04), while showing a significant overlap in Doppler waveform variables to the
      control group (p range 0.08-0.97). CONCLUSIONS: Similar to patients with
      glaucoma, individuals with ODD have low blood flow velocities in the vessels
      around the optic nerve head. Unlike patients with glaucoma, however, their CRA's
      blood flow velocity patterns correlate with the extent of the visual field
      defects.

PMID- 24456174
TI  - The new pharmacognosy.

PMID- 24456175
TI  - Controlled manipulation of gadolinium-coordinated supramolecules by low
      temperature scanning tunneling microscopy.
AB  - Coordination bonding between para-quarterphenyl-dicarbonitrile linkers and
      gadolinium on Ag(111) has been exploited to construct pentameric mononuclear
      supramolecules, consisting of a rare-earth center surrounded by five molecular
      linkers. By employing a scanning tunneling microscope tip, a manipulation
      protocol was developed to position individual pentamers on the surface. In
      addition, the tip was used to extract and replace individual linkers yielding
      tetrameric, pentameric, nonameric, and dodecameric metallosupramolecular
      arrangements. These results open new avenues toward advanced nanofabrication
      methods and rare-earth nanochemistry by combining the versatility of metal-ligand
      interactions and atomistic manipulation capabilities. 

PMID- 24456176
TI  - Colloid centrifugation selects normal spermatozoa from polymorphic bull
      ejaculates: a case study.
AB  - Semen from a Western Finncattle bull exhibiting a highly polymorphic spermiogram
      was processed by colloid centrifugation using Androcoll-B, a species-specific
      silane-coated silica colloid. In the first experiment, Single Layer
      Centrifugation (SLC) was used to identify which density colloids were needed to
      separate different cell populations. Colloids of the two chosen densities were
      then used in a density gradient resulting in two sperm subpopulations, one
      containing nearly all normally sized spermatozoa and the other enriched for the
      macrocephalic spermatozoa. Microcephalic spermatozoa did not appear in either of
      the selected subpopulations. Using a combination of SLC and DGC with this species
      specific colloid, it was possible to separate the spermatozoa into different
      subpopulations, that is, a subpopulation containing nearly all normally sized
      spermatozoa, and another one enriched for the macrocephalic spermatozoa. Thus,
      colloid centrifugation could be used to select sufficient normal spermatozoa from
      a highly polymorphic ejaculate for AI, if desired. 

PMID- 24456177
TI  - Intra-abdominal pressure as a predictor of acute kidney injury in postoperative
      abdominal surgery.
AB  - OBJECTIVES: The purpose of this study was to determine if intra-abdominal
      pressure (IAP) could predict acute renal injury (AKI) in the postoperative period
      of abdominal surgeries, and which would be its cutoff value. PATIENTS AND
      METHODS: A prospective observational study was conducted in the period from
      January 2010 to March 2011 in the Intensive Care Units (ICUs) of the University
      Hospital of Botucatu Medical School, UNESP. Consecutive patients undergoing
      abdominal surgery were included in the study. Initial evaluation, at admission in
      ICU, was performed in order to obtain demographic, clinical surgical and
      therapeutic data. Evaluation of IAP was obtained by the intravesical method, four
      times per day, and renal function was evaluated during the patient's stay in the
      ICU until discharge, death or occurrence of AKI. RESULTS: A total of 60 patients
      were evaluated, 16 patients developed intra-abdominal hypertension (IAH), 45
      developed an abnormal IAP (>7 mmHg) and 26 developed AKI. The first IAP at the
      time of admission to the ICU was able to predict the occurrence of AKI (area
      under the receiver-operating characteristic curve was 0.669; p=0.029) with the
      best cutoff point (by Youden index method) >= 7.68 mmHg, sensitivity of 87%,
      specificity of 46% at this point. The serial assessment of this parameter did not
      added prognostic value to initial evaluation. CONCLUSION: IAH was frequent in
      patients undergoing abdominal surgeries during ICU stay, and it predicted the
      occurrence of AKI. Serial assessments of IAP did not provided better
      discriminatory power than initial evaluation.

PMID- 24456178
TI  - Clinical assessment of spectral modulation detection for adult cochlear implant
      recipients: a non-language based measure of performance outcomes.
AB  - OBJECTIVE: Spectral modulation detection (SMD) provides a psychoacoustic estimate
      of spectral resolution. The SMD threshold for an implanted ear is highly
      correlated with speech understanding and is thus a non-linguistic, psychoacoustic
      index of speech understanding. This measure, however, is time and equipment
      intensive and thus not practical for clinical use. Thus the purpose of the
      current study was to investigate the efficacy of a quick SMD task with the
      following three study aims: (1) to investigate the correlation between the long
      psychoacoustic, and quick SMD tasks, (2) to determine the test/retest variability
      of the quick SMD task, and (3) to evaluate the relationship between the quick SMD
      task and speech understanding. DESIGN: This study included a within-subjects,
      repeated-measures design. STUDY SAMPLE: Seventy-six adult cochlear implant
      recipients participated. RESULTS: The results were as follows: (1) there was a
      significant correlation between the long psychoacoustic, and quick SMD tasks, (2)
      the test-retest variability of the quick SMD task was highly significant and, (3)
      there was a significant positive correlation between the quick SMD task and
      monosyllabic word recognition. CONCLUSIONS: The results of this study represent
      the direct clinical translation of a research-proven task of SMD into a quick,
      clinically feasible format.

PMID- 24456180
TI  - Comments re Macrae (2013).

PMID- 24456179
TI  - Low-frequency signals support perceptual organization of implant-simulated speech
      for adults and children.
AB  - OBJECTIVE: Using signals processed to simulate speech received through cochlear
      implants and low-frequency extended hearing aids, this study examined the
      proposal that low-frequency signals facilitate the perceptual organization of
      broader, spectrally degraded signals. DESIGN: In two experiments, words and
      sentences were presented in diotic and dichotic configurations as four-channel
      noise-vocoded signals (VOC-only), and as those signals combined with the acoustic
      signal below 0.25 kHz (LOW-plus). Dependent measures were percent correct
      recognition, and the difference between scores for the two processing conditions
      given as proportions of recognition scores for VOC-only. The influence of
      linguistic context was also examined. STUDY SAMPLE: Participants had normal
      hearing. In all, 40 adults, 40 seven-year-olds, and 20 five-year-olds
      participated. RESULTS: Participants of all ages showed benefits of adding the low
      frequency signal. The effect was greater for sentences than words, but no effect
      of diotic versus dichotic presentation was found. The influence of linguistic
      context was similar across age groups, and did not contribute to the low
      frequency effect. Listeners who had poorer VOC-only scores showed greater low
      frequency effects. CONCLUSION: The benefit of adding a low-frequency signal to a
      broader, spectrally degraded signal derives in some part from its facilitative
      influence on perceptual organization of the sensory input.

PMID- 24456181
TI  - Effects of noise and audiovisual cues on speech processing in adults with and
      without ADHD.
AB  - OBJECTIVE: This study examined the interplay among internal (e.g. attention,
      working memory abilities) and external (e.g. background noise, visual
      information) factors in individuals with and without ADHD. DESIGN: A 2 * 2 * 6
      mixed design with correlational analyses was used to compare participant results
      on a standardized listening in noise sentence repetition task (QuickSin; Killion
      et al, 2004 ), presented in an auditory and an audiovisual condition as signal-to
      noise ratio (SNR) varied from 25-0 dB and to determine individual differences in
      working memory capacity and short-term recall. STUDY SAMPLE: Thirty-eight young
      adults without ADHD and twenty-five young adults with ADHD. RESULTS: Diagnosis,
      modality, and signal-to-noise ratio all affected the ability to process speech in
      noise. The interaction between the diagnosis of ADHD, the presence of visual
      cues, and the level of noise had an effect on a person's ability to process
      speech in noise. conclusion: Young adults with ADHD benefited less from visual
      information during noise than young adults without ADHD, an effect influenced by
      working memory abilities.

PMID- 24456182
TI  - Anastomotic leaks in colorectal surgery.
AB  - BACKGROUND: Anastomotic leaks are a serious complication of bowel surgery. This
      study aimed to evaluate the rate and severity, and identify risk factors for
      leaks in patients undergoing bowel anastomoses. METHODS: Prospective evaluation
      was performed on patients undergoing bowel surgery within a colorectal surgical
      unit. Anastomotic leak was defined and graded according to severity. A nurse
      independently collected the information. Stepwise logistic regression analysis
      was performed. RESULTS: Two thousand three hundred and sixty-three patients
      underwent 2994 anastomoses. Their median age was 64 years. Seven per cent were
      emergency operations. Anastomotic leak occurred in 82 patients (2.7%). Sixty
      three per cent of leaks were managed with drainage or re-operation. Ultra-low
      anterior resection (ULAR) was associated with the highest subgroup leak rate
      (7.3%). In multivariable analysis, independent predictors for a leak included
      'other' pathologies (iatrogenic injury, ischaemia, radiation enteritis) (P=0.016,
      odds ratio (OR): 6.3, 95% confidence interval (CI): 1.4-28.0), ULAR (P=0.001, OR:
      8.5, 95% CI: 2.3-31.2) and the surgeon (A: P<0.001, OR: 3.4, 95% CI: 2.1-5.6).
      CONCLUSION: Majority of predictors for anastomotic leak were fairly intuitive.
      Nonetheless, it was relevant to note the importance of the individual surgeon as
      an independent predictor for leaks.

PMID- 24456183
TI  - SSTY proteins co-localize with the post-meiotic sex chromatin and interact with
      regulators of its expression.
AB  - In mammals, X- and Y-encoded genes are transcriptionally shut down during male
      meiosis, but expression of many of them is (re)activated in spermatids after
      meiosis. Post-meiotic XY gene expression is regulated by active epigenetic marks,
      which are de novo incorporated in the sex chromatin of spermatids, and by
      repressive epigenetic marks inherited during meiosis; alterations in this process
      lead to male infertility. In the mouse, post-meiotic XY gene expression is known
      to depend on genetic information carried by the male-specific region of the Y
      chromosome long arm (MSYq). The MSYq gene Sly has been shown to be a key
      regulator of post-meiotic sex chromosome gene expression and is necessary for the
      maintenance/recruitment of repressive epigenetic marks on the sex chromatin, but
      studies suggest that another MSYq gene may also be required. The best candidate
      to date is Ssty, an MSYq multi-copy gene of unknown function. Here, we show that
      SSTY proteins are specifically expressed in round and elongating spermatids, and
      co-localize with post-meiotic sex chromatin. Moreover, SSTY proteins interact
      with SLY protein and its X-linked homolog SLX/SLXL1, and may be required for
      localization of SLX/SLY proteins in the spermatid nucleus and sex chromatin. Our
      data suggest that SSTY is a second MSYq factor involved in the control of XY gene
      expression during sperm differentiation. As Slx/Slxl1 and Sly genes have been
      shown to be involved in the XY intra-genomic conflict, which affects the
      offspring sex ratio, Ssty may constitute another player in this conflict.

PMID- 24456185
TI  - Electrical stimulation vs. standard care for chronic ulcer healing: a systematic
      review and meta-analysis of randomised controlled trials.
AB  - BACKGROUND: We conducted a systematic review to investigate the effect of
      electrical stimulation on ulcer healing compared to usual treatment and/or sham
      stimulation. This systematic review also aimed to investigate the effect of
      different types of electrical stimulation on ulcer size reduction. MATERIALS AND
      METHODS: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials
      (CENTRAL) were searched from inception to October 2013 on randomised controlled
      trials (RCTs), in English and on human subjects, which assessed the effect of
      electrical stimulation on ulcer size as compared to standard care and/or sham
      stimulation. Data from included RCTs were pooled with use of fixed and random
      effects meta-analysis of the weighted mean change differences between the
      comparator groups. Heterogeneity across studies was assessed with the I(2)
      statistic. RESULTS: Twenty-one studies were eligible for inclusion in the meta
      analysis. In six trials (n = 210), electrical stimulation improved mean
      percentage change in ulcer size over total studies periods by 24.62%, 95%
      confidence interval (CI) 19.98-29.27, P < 0.00001 with no heterogeneity. In three
      trials (n = 176), electrical stimulation insignificantly improved mean weekly
      change in ulcer size by 1.64%, 95% (CI) -3.81 to 7.09, P = 0.56 with significant
      heterogeneity (I(2) = 96%, P < 0.00001). In six trials (n = 266), electrical
      stimulation decreased ulcer size by 2.42 cm(2), 95% (CI) 1.66-3.17, P < 0.00001,
      with significant heterogeneity. In one trial (n = 16), electrical stimulation
      also insignificantly improved the mean daily percentage change in ulcer size by
      0.63%, 95% (CI) -0.12 to 1.37, P = 0.10, with significant heterogeneity.
      CONCLUSIONS: Electrical stimulation appears to increase the rate of ulcer healing
      and may be superior to standard care for ulcer treatment.

PMID- 24456184
TI  - An atrophic, telangiectatic patch at the distal border of the tongue: a mucous
      membrane manifestation of xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized
      by clinical and cellular sensitivity, pigmentary changes, and early development
      of malignancies in sun-exposed mucocutaneous and ocular structures due to a
      defective ability to repair intracellular DNA damage. Individuals with XP also
      have a greater frequency of oral cancer, particularly squamous cell carcinoma of
      the anterior third of the tongue. The current study reports four cases of XP that
      exhibited a characteristic crescent-shaped, atrophic, telangiectatic area on the
      distal border of the tongue and correlates this lesion with the development of
      tumors at this site during follow-up. The tongue lesion was photographed and
      biopsied in the four patients. During routine follow-up visits, new biopsies were
      performed if additional tongue lesions were observed. The studied lesions were
      similar in the four patients. During follow-up, squamous cell carcinoma developed
      in one patient and pyogenic granuloma developed in three patients and was
      relapsing in one. The lesion remained stable in one patient during the study. The
      atrophic and telangiectatic patches probably occur because of chronic sun damage
      to the exposed portion of the tongue, and this area has a high predisposition for
      the development of benign and malignant tumors. 

PMID- 24456186
TI  - Selective detection of acetone and hydrogen sulfide for the diagnosis of diabetes
      and halitosis using SnO(2) nanofibers functionalized with reduced graphene oxide
      nanosheets.
AB  - Sensitive detection of acetone and hydrogen sulfide levels in exhaled human
      breath, serving as breath markers for some diseases such as diabetes and
      halitosis, may offer useful information for early diagnosis of these diseases.
      Exhaled breath analyzers using semiconductor metal oxide (SMO) gas sensors have
      attracted much attention because they offer low cost fabrication,
      miniaturization, and integration into portable devices for noninvasive medical
      diagnosis. However, SMO gas sensors often display cross sensitivity to
      interfering species. Therefore, selective real-time detection of specific disease
      markers is a major challenge that must be overcome to ensure reliable breath
      analysis. In this work, we report on highly sensitive and selective acetone and
      hydrogen sulfide detection achieved by sensitizing electrospun SnO2 nanofibers
      with reduced graphene oxide (RGO) nanosheets. SnO2 nanofibers mixed with a small
      amount (0.01 wt %) of RGO nanosheets exhibited sensitive response to hydrogen
      sulfide (Rair/Rgas = 34 at 5 ppm) at 200  degrees C, whereas sensitive acetone
      detection (Rair/Rgas = 10 at 5 ppm) was achieved by increasing the RGO loading to
      5 wt % and raising the operation temperature to 350  degrees C. The detection
      limit of these sensors is predicted to be as low as 1 ppm for hydrogen sulfide
      and 100 ppb for acetone, respectively. These concentrations are much lower than
      in the exhaled breath of healthy people. This demonstrates that optimization of
      the RGO loading and the operation temperature of RGO-SnO2 nanocomposite gas
      sensors enables highly sensitive and selective detection of breath markers for
      the diagnosis of diabetes and halitosis. 

PMID- 24456187
TI  - Mast cell curve-response in partial Achilles tendon rupture after 830 nm
      phototherapy.
AB  - OBJECTIVE: The aim of this study was to quantify mast cells at different time
      intervals after partial Achilles tendon rupture in rats treated with low-level
      laser therapy (LLLT). BACKGROUND DATA: There is a high incidence of lesions and
      ruptures in the Achilles tendon that can take weeks and even months to heal
      completely. As the mast cells help in the healing repair phase, and LLLT has
      favorable effects on this tissue repair process, study of this modality on the
      quantity of mastocytes in the ruptured tendon is relevant. METHODS: Sixty Wistar
      rats were subjected to partial Achilles' tendon rupture by direct trauma,
      randomized into 10 groups, and then divided into the group treated with 80 mW
      aluminum gallium arsenide infrared laser diode, continuous wave, 2.8 W/cm(2)
      power density, 40 J/cm(2) energy density, and 1.12 J total energy, and the
      simulation group. Both the groups were subdivided according to the histological
      assessment period of the sample, either 6 h, 12 h, 24 h, 2 days, or 3 days after
      the rupture, to quantify the mastocytes in the Achilles' tendon. RESULTS: The
      group subjected to LLLT presented a greater quantity of mastocytes in the periods
      of 6 h, 12 h, 24 h, 2 days, and 3 days after rupture, compared with the
      simulation groups, but differences were detected between the sample assessment
      periods only in the simulation group. CONCLUSIONS: LLLT was shown to increase the
      quantity of mastocytes in the assessment periods compared with the simulation
      groups.

PMID- 24456188
TI  - 3-Pyridazinylnitrenes and 2-pyrimidinylnitrenes.
AB  - Mild flash vacuum thermolysis of tetrazolo[1,5-b]pyridazines 8T generates small
      amounts of 3-azidopyridazines 8A (8aA, IR 2145, 2118 cm(-1); 8bA, 2142 cm(-1)).
      Photolysis of the tetrazoles/azides 8T/8A in Ar matrix generates 3
      pyridazinylnitrenes 9, detected by ESR spectroscopy (9a: D/hc = 1.006; E/hc =
      0.003 cm(-1)). Cyanovinylcarbenes 11, derived from 4-diazobut-2-enenitriles 10,
      are also detected by ESR spectroscopy (11a: D/hc = 0.362; E/hc = 0.021 cm(-1)).
      Carbenes 11 rearrange to cyanoallenes 12 and 3-cyanocyclopropenes 13.
      Triazacycloheptatetraenes 20 were not observed in the photolyses of 8. Photolysis
      of tetrazolo[1,5-a]pyrimidines/2-azidopyridmidines 18T/18A in Ar matrices at 254
      nm yields 2-pyrimidinylnitrenes 19, observable by ESR, UV, and IR spectroscopy
      (19a: ESR: D/hc = 1.217; E/hc = 0.0052 cm(-1)). Excellent agreement with the
      calculated IR spectrum identifies the 1,2,4-triazacyclohepta-1,2,4,6-tetraenes 20
      (20a, 1969 cm(-1); 20b, 1979 cm(-1)). Compounds 20 undergo photochemical ring
      opening to 1-isocyano-3-diazopropenes 23. Further irradiation also causes Type II
      ring-opening of pyrimidinylnitrenes 19 to 2-(cyanimino)vinylnitrenes 21 (21a:
      D/hc = 0.875; E/hc = 0.00 cm(-1)), isomerization to cyaniminoketenimine 25 (2044
      cm(-1)), and cyclization to 1-cyanopyrazoles 22. The reaction mechanisms are
      discussed and supported by DFT calculations on key intermediates and pathways.
      There is no evidence for the interconversion of 3-pyridazinylnitrenes 9 and 2
      pyrimidinylnitrenes 19. 

PMID- 24456189
TI  - A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression
      profiles for vegetative tissues of grain, sweet and bioenergy sorghums.
AB  - BACKGROUND: Effective improvement in sorghum crop development necessitates a
      genomics-based approach to identify functional genes and QTLs. Sequenced in 2009,
      a comprehensive annotation of the sorghum genome and the development of
      functional genomics resources is key to enable the discovery and deployment of
      regulatory and metabolic genes and gene networks for crop improvement. RESULTS:
      This study utilizes the first commercially available whole-transcriptome sorghum
      microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression
      patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains
      1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor
      nuclear, chloroplast, and mitochondrial genomes. Specific probesets were also
      included for putative non-coding RNAs that may play a role in gene regulation
      (e.g., microRNAs), and confirmed functional small RNAs in related species (maize
      and sugarcane) were also included in our array design. We generated expression
      data for 78 samples with a combination of four different tissue types (shoot,
      root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse
      genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611,
      AR2400 and PI455230) representing grain, sweet, forage, and high biomass
      ideotypes. CONCLUSIONS: Here we present a summary of the microarray dataset,
      including analysis of tissue-specific gene expression profiles and associated
      expression profiles of relevant metabolic pathways. With an aim to enable
      identification and functional characterization of genes in sorghum, this
      expression atlas presents a new and valuable resource to the research community.

PMID- 24456191
TI  - Model for photoinduced bending of slender molecular crystals.
AB  - The growing realization that photoinduced bending of slender photoreactive single
      crystals is surprisingly common has inspired researchers to control crystal
      motility for actuation. However, new mechanically responsive crystals are
      reported at a greater rate than their quantitative photophysical
      characterization; a quantitative identification of measurable parameters and
      molecular-scale factors that determine the mechanical response has yet to be
      established. Herein, a simple mathematical description of the quasi-static and
      time-dependent photoinduced bending of macroscopic single crystals is provided.
      This kinetic model goes beyond the approximate treatment of a bending crystal as
      a simple composite bilayer. It includes alternative pathways for excited-state
      decay and provides a more accurate description of the bending by accounting for
      the spatial gradient in the product/reactant ratio. A new crystal form (space
      group P21/n) of the photoresponsive azo-dye Disperse Red 1 (DR1) is analyzed
      within the constraints of the aforementioned model. The crystal bending kinetics
      depends on intrinsic factors (crystal size) and external factors (excitation
      time, direction, and intensity). 

PMID- 24456192
TI  - Investigation of the mechanisms underlying the high acetylene-reducing activity
      exhibited by the soil bacterial community from BC2 horizon in the permafrost zone
      of the East Siberian larch forest bed.
AB  - AIMS: This study addressed a microbial composition of East Siberian larch forest
      bed soil and focused on major nitrogen-fixing bacterial consortia showing the
      highest capacity to induce acetylene reduction. METHODS AND RESULTS: The ability
      of a soil microbial consortium to effectively reduce acetylene was investigated
      using gellan gum medium. In parallel, each microbial component in the medium was
      analysed by a 16S rRNA gene-targeting denaturing gradient gel electrophoresis
      (DGGE), together with an attempt to isolate pure culture of the culturable
      eubacteria. Six strains of the isolated bacteria were characterized as
      diazotrophs, and Burkholderia xenovorans was found to be one of the major
      nitrogen fixer in the bacterial community cultured from the BC2 horizon soil
      microbiota. Co-culturing of either a diazotrophic Pseudomonas sp. with a
      nondiazotrophic Luteibacter sp. or a diazotrophic Luteibacter sp. with a
      nondiazotrophic bacterium B. xenovorans resulted in a marked elevation in
      acetylene reduction over that observed in the pure culture of each diazotroph.
      CONCLUSIONS: A promotion of acetylene reduction in mixed bacterial cultures,
      particularly when the cultures included Luteibacter, was clearly observed due to
      an increase in the bacterial cell population. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Our study, which showed that some unculturable bacteria including
      anaerobic Clostridium sp. that can provide major contribution to nitrogen
      fixation, may provide key information useful in identifying the 'missing link' in
      the nitrogen cycle in the cryogenic soil ecosystem of boreal forests.

PMID- 24456193
TI  - Extensive energy landscape sampling of nanotube end-caps reveals no chiral-angle
      bias for their nucleation.
AB  - In the formation of a carbon nanotube (CNT) nucleus, a hemispherical fullerene
      end-cap, a specific pattern of six pentagons encodes what unique (n,m) chirality
      a nascent CNT would inherit, with many possible pentagon patterns corresponding
      to a single chirality. This configurational variety and its potential role in the
      initial stages of CNT catalytic growth remain essentially unexplored. Here we
      present large-scale calculations designed to evaluate the intrinsic energies of
      all possible CNT caps for selected chiralities corresponding to tube diameters d
      ? 1 nm. Our quantitative analysis reveals that for all chiral angles chi the
      energy scale variability associated with the CNT caps is small, compared to that
      of the CNT/catalyst interface. Such a flat energy landscape cannot therefore be a
      dominant factor for chiral distribution and lends further credibility to
      interface-controlled scenarios for selective growth of single-walled CNT of
      desired chirality. 

PMID- 24456194
TI  - Ocular pulse amplitude and Doppler waveform analysis in glaucoma patients.
AB  - PURPOSE: To determine the correlation between ocular blood flow velocities and
      ocular pulse amplitude (OPA) in glaucoma patients using colour Doppler imaging
      (CDI) waveform analysis. METHOD: A prospective, observer-masked, case-control
      study was performed. OPA and blood flow variables from central retinal artery and
      vein (CRA, CRV), nasal and temporal short posterior ciliary arteries (NPCA, TPCA)
      and ophthalmic artery (OA) were obtained through dynamic contour tonometry and
      CDI, respectively. Univariate and multiple regression analyses were performed to
      explore the correlations between OPA and retrobulbar CDI waveform and systemic
      cardiovascular parameters (blood pressure, blood pressure amplitude, mean ocular
      perfusion pressure and peripheral pulse). RESULTS: One hundred and ninety-two
      patients were included [healthy controls: 55; primary open-angle glaucoma (POAG):
      74; normal-tension glaucoma (NTG): 63]. OPA was statistically different between
      groups (Healthy: 3.17 +/- 1.2 mmHg; NTG: 2.58 +/- 1.2 mmHg; POAG: 2.60 +/- 1.1
      mmHg; p < 0.01), but not between the glaucoma groups (p = 0.60). Multiple
      regression models to explain OPA variance were made for each cohort (healthy: p <
      0.001, r = 0.605; NTG: p = 0.003, r = 0.372; POAG: p < 0.001, r = 0.412). OPA was
      independently associated with retrobulbar CDI parameters in the healthy subjects
      and POAG patients (healthy CRV resistance index: beta = 3.37, CI: 0.16-6.59;
      healthy NPCA mean systolic/diastolic velocity ratio: beta = 1.34, CI: 0.52-2.15;
      POAG TPCA mean systolic velocity: beta = 0.14, CI 0.05-0.23). OPA in the NTG
      group was associated with diastolic blood pressure and pulse rate (beta = -0.04,
      CI: -0.06 to -0.01; beta = -0.04, CI: -0.06 to -0.001, respectively).
      CONCLUSIONS: Vascular-related models provide a better explanation to OPA variance
      in healthy individuals than in glaucoma patients. The variables that influence
      OPA seem to be different in healthy, POAG and NTG patients.

PMID- 24456195
TI  - Allergic reaction to the tetracycline component of Ledermix paste: a case report.
AB  - AIM: Allergy to materials used during root canal treatment is well recognized in
      the endodontic literature. However, allergy to Ledermix paste, a compound
      containing triamcinolone (a corticosteroid) and demeclocycline (a tetracycline
      antibiotic), has not been reported apart from one very recent case in a Letter to
      the Editor of a journal. The aim of this report is to describe a proven allergic
      reaction to tetracycline following the use of Ledermix paste as a root canal
      medicament. SUMMARY: A 33-year-old female patient undergoing root canal
      retreatment of her right mandibular second premolar tooth experienced symptoms of
      type 1 allergy following the placement of an intracanal medicament containing a
      mixture of Ledermix paste and calcium hydroxide [Ca(OH)2 ]. Signs of the type 1
      allergy included urticaria, pruritus all over the body, general malaise and
      fever. These all subsided after removing and flushing out the Ledermix paste
      Ca(OH)2 mixture and redressing the root canal with Ca(OH)2 alone. Allergic
      scratch tests were performed, and these confirmed that the patient was allergic
      to tetracycline, one of the components of Ledermix paste.

PMID- 24456196
TI  - Different neural manifestations of two slow frequency bands in resting functional
      magnetic resonance imaging: a systemic survey at regional, interregional, and
      network levels.
AB  - Temporal and spectral perspectives are two fundamental facets in deciphering
      fluctuating signals. In resting state, the dynamics of blood oxygen level
      dependent (BOLD) signals recorded by functional magnetic resonance imaging (fMRI)
      have been proven to be strikingly informative (0.01-0.1 Hz). The distinction
      between slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) has been described,
      but the pertinent data have never been systematically investigated. This study
      used fMRI to measure spontaneous brain activity and to explore the different
      spectral characteristics of slow-4 and slow-5 at regional, interregional, and
      network levels, respectively assessed by regional homogeneity (ReHo) and mean
      amplitude of low-frequency fluctuation (mALFF), functional connectivity (FC)
      patterns, and graph theory. Results of paired t-tests supported/replicated recent
      research dividing low-frequency BOLD fluctuation into slow-4 and slow-5 for ReHo
      and mALFF. Interregional analyses showed that for brain regions reaching
      statistical significance, FC strengths at slow-4 were always weaker than those at
      slow-5. Community detection algorithm was applied to FC data and unveiled two
      modules sensitive to frequency effects: one comprised sensorimotor structure, and
      the other encompassed limbic/paralimbic system. Graph theoretical analysis
      verified that slow-4 and slow-5 differed in local segregation measures. Although
      the manifestation of frequency differences seemed complicated, the associated
      brain regions can be grossly categorized into limbic/paralimbic, midline, and
      sensorimotor systems. Our results suggest that future resting fMRI research
      addressing the three above systems either from neuropsychiatric or psychological
      perspectives may consider using spectrum-specific analytical strategies.

PMID- 24456197
TI  - Direct access to functionalized azepanes by cross-coupling with alpha-halo
      eneformamides.
AB  - The synthesis of functionalized azepanes was accomplished through the palladium
      mediated cross-coupling of alpha-halo eneformamides with mostly unactivated
      nucleophiles under mild conditions. Alkenylations proceeded with excellent
      stereoselectivitiy. In most cases, high yields of the coupling products were
      obtained. 

PMID- 24456198
TI  - Time to adjuvant chemotherapy following colorectal cancer resection is associated
      with an improved survival.
AB  - AIM: Multicentre randomized trials have demonstrated equivalent long-term
      outcomes for open and laparoscopic resection of colon cancer. Some studies have
      indicated a possible survival advantage in certain patients undergoing
      laparoscopic resection. Patients who receive adjuvant chemotherapy in < 8 weeks
      following surgery can have an improved survival. METHOD: Data were collated for
      patients having an elective laparoscopic or open resection for non-metastatic
      colorectal cancer between October 2003 and December 2010 and subsequently having
      adjuvant chemotherapy. Survival analysis was conducted. RESULTS: In all, 209
      patients received adjuvant chemotherapy following open (n = 76) or laparoscopic
      (n = 133) surgery. Median length of stay was 3 days with laparoscopic resection
      and 6 days with open resection (P < 0.0005). Median number of days to initiation
      of adjuvant chemotherapy was 52 with laparoscopic resection and 58 with open
      resection (P = 0.008). The 5-year overall survival was 89.6% in patients
      receiving chemotherapy in < 8 weeks after surgery, compared with 73.5% who
      started the treatment over 8 weeks (P = 0.016). The 5-year overall survival for
      those patients with a laparoscopic resection was 82.3% compared with 80.3% with
      an open resection (P = 0.049). CONCLUSION: There is an overall survival advantage
      when patients receive adjuvant chemotherapy < 8 weeks after surgery. Laparoscopic
      resection allows earlier discharge and, subsequently, earlier initiation of
      adjuvant chemotherapy.

PMID- 24456199
TI  - Initial cutaneous manifestations of Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare, uniformly fatal, premature
      aging disease with distinct dermatologic features. We sought to identify and
      describe the initial skin and hair findings as potential diagnostic signs of the
      disease. We performed a chart review of the structured initial intake histories
      of 39 individuals with HGPS enrolled in clinical trials from 2007 to 2010 at
      Boston Children's Hospital, limited to cutaneous history from birth to 24 months.
      Medical photographs were provided through the clinical trials and the Progeria
      Research Foundation Medical and Research Database at Brown University Center for
      Gerontology and Healthcare Research. All 39 patients reported skin and hair
      abnormalities within the first 24 months of life. Pathologies included
      sclerodermoid change, prominent superficial veins, dyspigmentation, and alopecia.
      The mean age of presentation for each finding was <12 months. The most frequently
      reported skin feature was sclerodermoid change, which commonly involved the
      abdomen and bilateral lower extremities. Prominent superficial vasculature
      manifested as circumoral cyanosis and pronounced veins on the scalp and body.
      Hypo- and hyperpigmentation were observed over areas of sclerodermoid change.
      Scalp alopecia progressed in a distinct pattern, with preservation of the hair
      over the midscalp and vertex areas for the longest period of time. HGPS has
      distinct cutaneous manifestations during the first 2 years of life that may be
      the first signs of disease. Awareness of these findings could expedite diagnosis.

PMID- 24456200
TI  - Gut on the floor: vaginal evisceration.

PMID- 24456202
TI  - Deletion of Vitamin C biosynthesis enzyme, Arabino-1, 4-lactone oxidase in
      Leishmania donovani results in increased pro-inflammatory responses from host
      immune cells.
AB  - Recently, we reported molecular characterization, localization and functional
      importance of Arabino-1, 4-lactone oxidase (ALO) enzyme from Leishmania donovani
      that catalyses the last step in ascorbate biosynthesis pathway. Vitamin C (l
      ascorbic acid) is implicated in several crucial physiological processes. To
      elucidate the biological role of d-arabinono-gamma-lactone oxidase in Leishmania,
      we made L. donovani ALO null mutant (DeltaALO) by double targeted gene
      replacement. This mutant lacked ALO activity, showed transient growth defect and
      reduced ascorbate levels. DeltaALO grown in ascorbate depleted media further
      enhanced growth defect with no detectable levels of ascorbate, implying that
      parasites have the ability to scavenge ascorbate. DeltaALO mutants showed reduced
      survival in mouse macrophages and are impaired in their infectivity in vivo.
      Furthermore, the DeltaALO mutant induced production of pro-inflammatory cytokines
      gamma interferon (IFN-gamma), interleukin-12 (IL-12) and tumour necrosis factor
      alpha (TNF-alpha) by infected mouse macrophages. These mutants were susceptible
      to oxidative stresses in vitro as revealed by the decreased survival inside
      macrophages by increased production of reactive oxygen or nitrogen species.
      Complementation of the DeltaALO mutants restored the phenotypic effects in these
      parasites. Our description of ALO null mutant parasite that triggers pro
      inflammatory host responses provides a novel platform for targeting ALO in anti
      parasitic strategies. 

PMID- 24456201
TI  - Ubiquitin-activating enzyme E1 inhibitor PYR41 attenuates angiotensin II-induced
      activation of dendritic cells via the IkappaBa/NF-kappaB and MKP1/ERK/STAT1
      pathways.
AB  - The activation of dendritic cells (DCs) is necessary to initiate immune
      responses. Angiotensin II (Ang II) can enhance the maturation and activation of
      DCs, but the mechanisms are still unclear. Ubiquitin-activating enzyme (E1/Uba1)
      is the common first step in ubiquitylation, which decides whether or not the
      modified protein is ultimately degraded by the proteasome. This study aimed to
      investigate the role of E1 in Ang II-induced activation of DCs and the underlying
      mechanisms. First, we showed that Ang II stimulation significantly up-regulated
      E1 expression in DCs. Moreover, Ang II treatment markedly induced phenotypic
      maturation, the secretion of cytokines and the immunostimulatory capacity of DCs.
      In contrast, inhibition of E1 by a small molecule inhibitor, 4 [4-(5-nitro-furan
      2-ylmethylene)-3, 5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (PYR41),
      markedly attenuated these effects. Mechanistically, PYR41 treatment markedly
      decreased K63-linked ubiquitination of tumour necrosis factor receptor-associated
      factor 6 and nuclear factor-kappaB essential modulator, inhibited proteasomal
      degradation of nuclear factor-kappaB inhibitor alpha and mitogen-activated
      protein kinase phosphatase 1 thereby resulting in activation of nuclear factor
      kappaB, extracellular signal-regulated kinase 1/2 and signal transducer and
      activator of transcription 1 signalling pathways in DCs induced by Ang II. Taken
      together, our results demonstrate a novel role of E1 in Ang II-induced activation
      of DCs, and inhibition of E1 activity might be a potential therapeutic target for
      DC-mediated autoimmune diseases.

PMID- 24456203
TI  - Quality of emergency medical care in Gondar University Referral Hospital,
      Northwest Ethiopia: a survey of patients' perspectives.
AB  - BACKGROUND: Ethiopia has fairly good coverage but very low utilization of health
      care services. Emergency medical care services require fast, correct and curious
      services to clients as they present with acute problems. In Ethiopia and Gondar
      in particular, the quality of emergency medical care has not been studied. The
      main aim of this study was to assess the disease profile and patients'
      satisfaction in Gondar University Referral Hospital (GURH). METHODS: A facility
      based cross-sectional study was conducted among patients visiting GURH for
      emergency care. Ethical clearance was obtained from the Institutional Review
      Board of University of Gondar. Patients were selected by systematic random
      sampling, using patient flow list in the day and night emergency services. Data
      were collected using a standard Press Ganey questionnaire by BSc health science
      graduates. Data were entered in to Epi Info 3.5.3 software and exported to SPSS
      version 20.0 for windows for analysis. RESULTS: A total of 963 patients (response
      rate = 96.8%) were studied. The mean (+ s.d.) age of patients was 28.4 (+17.9)
      years. The overall satisfaction using the mean score indicates that 498 (51.7%)
      95%CI: (48.4% - 54.9%) were satisfied with the service, the providers and the
      facility suitability whereas 465(48.3%) 95%CI: (45.1%- 51.6%) were not satisfied.
      Seven hundred and six (73.3%) 95%CI: 70.4%-76.1%, patients reported that they
      have been discriminated or treated badly during the service provision in the
      hospital. OPD site visited (p < 0.0001), visiting days of the week (P < 0.049),
      medical condition on arrival (P < 0.0001), degree of confidence in the hospital
      (AOR = 1.9, 95%CI: 1.1, 3.1), reported discrimination/bad treatment of patients
      with service (AOR = 0.4, 95%CI: 0.2, 0.7), were significantly associated
      determinants of patient satisfaction. CONCLUSIONS: Non-communicable disease
      emergencies like injuries and cardiovascular diseases are common. There is a low
      level of patient satisfaction related to lack of confidence in the hospital for
      treatment, discrimination towards patient care, and under and delayed treatment
      of patients who were not in serious medical conditions. Hospitals shall prepare
      themselves to address the increasing challenge of non-communicable disease
      emergencies. It is important to revise the service delivery in the emergency
      department to improve staff courtesy and politeness, commitment, reduce
      discrimination and bad treatment and proper triage of emergencies at all points
      of care to increase patient satisfaction giving emphasis to earlier working days.

PMID- 24456204
TI  - Could mini-PET be used to instead of 4 h original-PET to assess peritoneal
      permeability in children on peritoneal dialysis?
AB  - BACKGROUND: Original peritoneal equilibration test (PET) is an implementation
      that requires hard work for peritoneal dialysis (PD) staff. Therefore, several
      authors have attempted to validate short and fast PET protocols, with
      controversial results. The aim of this study was to evaluate the concordance
      between the mini-PET and original PET in children. METHODS: In 26 stable
      continuous ambulatory PD patients, we performed an original PET with 2.27% (4 h)
      and a mini-PET with 3.86% glucose PD fluid (1 h) and compared ultrafiltration
      (UF) and small solute transports obtained with the two methods. RESULTS: Twenty
      six children, 14 males, mean age 11.4 +/- 5.6 (range 2.5-19 years), were
      included. Meantime on PD at time of enrollment was 35.2 +/- 24.5 months (range 6
      84 months). Based on the 4-h creatinine D/P data, the number of the patients
      within each transport category was as follow: high, 5; average, 18; low, 3. Kappa
      test showed a significant concordance between original PET and mini-PET
      (k=0.610). Based on the 4-h glucose D/D0 data, the number of the patients within
      each transport category was as follow: high, 5; average, 17; low, 4. Kappa test
      showed a moderate agreement between original PET and mini-PET (0.514, p=0.000).
      When Pearson correlation analysis between original PET and mini-PET was
      performed, there were significant positive correlations between original 2.27%
      PET and mini-PET (r=0.720, p=0.000, r=0.638, p=0.000, respectively). When
      comparing the numeric results of mini-PET and 4 h of original PET for
      D/Creatinine, by simple regression analysis, we found statistically significant
      correlation among PETs. CONCLUSIONS: In this study, we showed concordance between
      the mini-PET and original PET. The 3.86% mini-PET is simple and fast methods to
      assess free water transport. This also gives information about total UF and small
      solute transports and it is in good agreement with the original PET.

PMID- 24456205
TI  - Organocatalytic preparation of substituted cyclopentanes: a mechanistic study.
AB  - The reaction mechanism of a tandem conjugate addition/alpha-alkylation of enals
      leading to functionalized cyclopentanes catalyzed by O
      trimethylsilyldiphenylprolinol was investigated by mass spectrometry, NMR
      spectroscopy, and DFT calculations. We have shown that the high stereoselectivity
      of the reaction depends on the energy discrimination between the two
      stereoisomers formed by the condensation of the alpha,beta-unsaturated aldehyde
      (cinnamaldehyde) and the catalyst. The stereoselectivity of this step depends on
      the solvent used. The experimental activation barriers were determined to be E(a)
      = 25 +/- 7 kJ mol(-1) (Arrhenius equation), DeltaH(?) = 23 +/- 7 kJ mol(-1), and
      DeltaG(?) = 101 +/- 9 kJ mol(-1) (Eyring equation).

PMID- 24456206
TI  - Evaluation of calcium supplementation with algae (Lithothamnion muelleri) on
      metabolic and inflammatory parameters in mice fed a high refined carbohydrate
      containing diet.
AB  - The aim of the present study was to evaluate the potential of calcium
      supplementation from Lithothamnium muelleri algae on metabolic and inflammatory
      parameters in mice with increased adiposity. Male mice were fed and divided
      during 8 weeks in: control (C), a high refined carbohydrate-containing diet (HC),
      HC diet supplemented with 1% of Lithothamnion muelleri algae (HC + A) and HC diet
      supplemented with 0.9% calcium carbonate (HC + C). Animals fed HC diet had
      increased body weight gain and adiposity, serum glucose and cholesterol, glucose
      intolerance and decreased insulin sensitivity, compared to control diet. However,
      the HC + A and HC + C groups did not prevent these aspects and were not able to
      change the CD14 + cells population in adipose tissue of animals fed HC diet.
      Calcium supplementation with Lithothamnium muelleri algae and calcium carbonate
      had no protective effect against the development of adiposity, metabolic and
      inflammatory alterations induced by HC diet.

PMID- 24456207
TI  - A mechanistic mathematical model for the catalytic action of glutathione
      peroxidase.
AB  - Glutathione peroxidase (GPx) is a well-known seleno-enzyme that protects cells
      from oxidative stress (e.g., lipid peroxidation and oxidation of other cellular
      proteins and macromolecules), by catalyzing the reduction of harmful peroxides
      (e.g., hydrogen peroxide: H2O2) with reduced glutathione (GSH). However, the
      catalytic mechanism of GPx kinetics is not well characterized in terms of a
      mathematical model. We developed here a mechanistic mathematical model of GPx
      kinetics by considering a unified catalytic scheme and estimated the unknown
      model parameters based on different experimental data from the literature on the
      kinetics of the enzyme. The model predictions are consistent with the consensus
      that GPx operates via a ping-pong mechanism. The unified catalytic scheme
      proposed here for GPx kinetics clarifies various anomalies, such as what are the
      individual steps in the catalytic scheme by estimating their associated rate
      constant values and a plausible rationale for the contradicting experimental
      results. The developed model presents a unique opportunity to understand the
      effects of pH and product GSSG on the GPx activity under both physiological and
      pathophysiological conditions. Although model parameters related to the product
      GSSG were not identifiable due to lack of product-inhibition data, the
      preliminary model simulations with the assumed range of parameters show that the
      inhibition by the product GSSG is negligible, consistent with what is known in
      the literature. In addition, the model is able to simulate the bi-modal behavior
      of the GPx activity with respect to pH with the pH-range for maximal GPx activity
      decreasing significantly as the GSH levels decrease and H2O2 levels increase
      (characteristics of oxidative stress). The model provides a key component for an
      integrated model of H2O2 balance under normal and oxidative stress conditions.

PMID- 24456209
TI  - Cutaneous metastasis of prostate cancer: a case report and review of the
      literature with bioinformatics analysis of multiple healthcare delivery networks.
AB  - Distant cutaneous metastases of prostate carcinomas are extremely rare, despite
      its high incidence and prevalence. Most cases are either a result of local
      extension, such as into seminal vesicles or distant metastases to bone. Few cases
      of true cutaneous metastatic prostate carcinoma exist in the literature.
      Clinically, cutaneous prostate carcinoma has been reported to mimic many other
      conditions, such as cellulitis, sebaceous cysts, zosteriform lesions,
      telangectasias and more, resulting in poor recognition. We report a case of
      distant cutaneous metastasis of prostate carcinoma and recent review of the
      literature with an analysis of de-identified patient records from multiple
      healthcare delivery networks. A diagnosis of metastatic prostate carcinoma may
      have been easily overlooked given the location and nature of the rash. Reviewing
      case reports and using aggregated electronic health records (EHRs), we find that
      fewer than 0.1% of all prostate carcinomas result in cutaneous metastases,
      compared with much higher rates in other types of cancers. Coupled with the low
      frequency of metastases to skin, careful consideration must be taken when
      evaluating a rash in a patient with a prior history of cancer. A complete
      clinical history and strong suspicion would be required to make a diagnosis of
      cutaneous metastases of the prostate. 

PMID- 24456208
TI  - Poly(amidoamine) dendrimer-enabled simultaneous stabilization and
      functionalization of electrospun poly(gamma-glutamic acid) nanofibers.
AB  - We report a facile and general approach to using generation 2 (G2)
      poly(amidoamine) (PAMAM) dendrimers for simultaneous stabilization and
      functionalization of electrospun poly(gamma-glutamic acid) nanofibers (gamma-PGA
      NFs). In this study, uniform gamma-PGA NFs with a smooth morphology were
      generated using electrospinning technology. In order to endow the NFs with good
      water stability, amine-terminated G2.NH2 PAMAM dendrimers were utilized to
      crosslink the gamma-PGA NFs via 1-ethyl-3-(3-dimethylami-nopropyl) carbodiimide
      coupling chemistry. Under the optimized crosslinking conditions, G2.NH2
      dendrimers partially modified with fluorescein isothiocyanate (FI) or folic acid
      (FA) were used to crosslink gamma-PGA NFs. Our results reveal that G2.NH2-FI is
      able to simultaneously render the NFs with good water stability and fluorescence
      property, while G2.NH2-FA is able to simultaneously endow the NFs with water
      stability and the ability to capture FA receptor-overexpressing cancer cells in
      vitro via ligand-receptor interaction. With the tunable dendrimer surface
      chemistry, multifunctional water-stable gamma-PGA-based NFs may be generated via
      a dendrimer crosslinking approach, thereby providing diverse applications in the
      areas of biosensing, tissue engineering, drug delivery, and environmental
      sciences. 

PMID- 24456210
TI  - Scent-evoked nostalgia.
AB  - Can scents evoke nostalgia; what might be the psychological implications of such
      an evocation? Participants sampled 12 scents and rated the extent to which each
      scent was familiar, arousing and autobiographically relevant, as well as the
      extent to which each scent elicited nostalgia. Participants who were high
      (compared to low) in nostalgia proneness reported more scent-evoked nostalgia,
      and scents elicited greater nostalgia to the extent that they were arousing,
      familiar and autobiographically relevant. Scent-evoked nostalgia predicted higher
      levels of positive affect, self-esteem, self-continuity, optimism, social
      connectedness and meaning in life. In addition, scent-evoked nostalgia was
      characterised by more positive emotions than either non-nostalgic
      autobiographical memories or non-nostalgic non-autobiographical memories.
      Finally, scent-evoked nostalgia predicted in-the-moment feelings of personal
      (general or object-specific) nostalgia. The findings represent a foray into
      understanding the triggers and affective signature of scent-evoked nostalgia. 

PMID- 24456211
TI  - Allosteric regulation and substrate activation in cytosolic nucleotidase II from
      Legionella pneumophila.
AB  - Cytosolic nucleotidase II (cN-II) from Legionella pneumophila (Lp) catalyzes the
      hydrolysis of GMP and dGMP displaying sigmoidal curves, whereas catalysis of IMP
      hydrolysis displayed a biphasic curve in the initial rate versus substrate
      concentration plots. Allosteric modulators of mammalian cN-II did not activate
      LpcN-II although GTP, GDP and the substrate GMP were specific activators. Crystal
      structures of the tetrameric LpcN-II revealed an activator-binding site at the
      dimer interface. A double mutation in this allosteric-binding site abolished
      activation, confirming the structural observations. The substrate GMP acting as
      an activator, partitioning between the allosteric and active site, is the basis
      for the sigmoidicity of the initial velocity versus GMP concentration plot. The
      LpcN-II tetramer showed differences in subunit organization upon activator
      binding that are absent in the activator-bound human cN-II structure. This is the
      first observation of a structural change induced by activator binding in cN-II
      that may be the molecular mechanism for enzyme activation. DATABASE: The
      coordinates and structure factors reported in this paper have been submitted to
      the Protein Data Bank under the accession numbers 2BDE and 4G63. The accession
      number of GMP complexed LpcN-II is 4OHF. STRUCTURED DIGITAL ABSTRACT: LpcN-II and
      LpcN-II bind by molecular sieving (View interaction) LpcN-II and LpcN-II bind by
      x-ray crystallography (View interaction) [Structured digital abstract was added
      on 5 March 2014 after original online publication].

PMID- 24456213
TI  - Reverse micelles as a platform for dynamic nuclear polarization in solution NMR
      of proteins.
AB  - Despite tremendous advances in recent years, solution NMR remains fundamentally
      restricted due to its inherent insensitivity. Dynamic nuclear polarization (DNP)
      potentially offers significant improvements in this respect. The basic DNP
      strategy is to irradiate the EPR transitions of a stable radical and transfer
      this nonequilibrium polarization to the hydrogen spins of water, which will in
      turn transfer polarization to the hydrogens of the macromolecule. Unfortunately,
      these EPR transitions lie in the microwave range of the electromagnetic spectrum
      where bulk water absorbs strongly, often resulting in catastrophic heating.
      Furthermore, the residence times of water on the surface of the protein in bulk
      solution are generally too short for efficient transfer of polarization. Here we
      take advantage of the properties of solutions of encapsulated proteins dissolved
      in low viscosity solvents to implement DNP in liquids. Such samples are largely
      transparent to the microwave frequencies required and thereby avoid significant
      heating. Nitroxide radicals are introduced into the reverse micelle system in
      three ways: attached to the protein, embedded in the reverse micelle shell, and
      free in the aqueous core. Significant enhancements of the water resonance ranging
      up to ~-93 at 0.35 T were observed. We also find that the hydration properties of
      encapsulated proteins allow for efficient polarization transfer from water to the
      protein. These and other observations suggest that merging reverse micelle
      encapsulation technology with DNP offers a route to a significant increase in the
      sensitivity of solution NMR spectroscopy of proteins and other biomolecules. 

PMID- 24456214
TI  - Cord blood graft composition impacts the clinical outcome of allogeneic stem cell
      transplantation.
AB  - INTRODUCTION: Despite routine use of umbilical cord blood (CB) grafts as stem
      cell source for allogeneic stem cell transplantations, much remains unknown
      regarding their cell composition and correlation with clinical outcome. METHODS:
      We analyzed material from 30 CB units used for allogeneic hematopoietic stem cell
      transplantation by multicolor flow cytometry. Phenotypic data were correlated
      with various clinical outcomes such as survival, graft-versus-host disease
      (GVHD), relapse, rejection, viral reactivation, and bacteremia. RESULTS: We found
      that above-median frequencies of CD69+ T cells, naive CD8+ T cells, and CD127+ B
      cells in the CB graft were each associated with significantly improved patient
      survival. Moreover, a statistically significant correlation was seen between
      higher levels of CD94+ T cells and herpes simplex virus and varicella zoster
      virus reactivation post transplantation. A similar correlation was seen for the
      frequency of CD95+ cells in total CD3+, as well as CD4+ and CD8+ T-cell subsets,
      and viral reactivation. Finally, a higher frequency of naive CD8+ T cells was
      associated with the incidence of acute GVHD. CONCLUSION: Our study highlights the
      importance of further exploration of graft composition before CB transplantation
      as a tool for risk prediction.

PMID- 24456215
TI  - Carbon nanotubes: a potential concept for drug delivery applications.
AB  - The unique properties of carbon nanotubes (CNTs) make them a highly interesting
      and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient
      delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and
      lot more. Even though highly beneficial, the biocompatibility of CNTs is a major
      issue in their questioning their potential application in targeting drug
      delivery. Studies confirmed subdued toxicity of CNTs following slight
      modifications like functionalization, controlled dimensions, purification etc. A
      well-established mechanism for cellular internalization is an insistent need to
      attain a more efficient and targeted delivery. Recent patents have been
      thoroughly discussed in the text below. 

PMID- 24456216
TI  - Efficacy of xylene and passive ultrasonic irrigation on remaining root filling
      material during retreatment of anatomically complex teeth.
AB  - AIM: To evaluate the volume of remaining filling material in the mesial root
      canals of mandibular molars after root canal retreatment with different
      procedures performed sequentially. METHODOLOGY: The mesial root canals of 12
      human first mandibular molars were instrumented using the BioRace system until a
      size 25, .06 taper instrument. The mesial roots were filled with gutta-percha and
      AH-Plus using a vertical compaction technique. The specimens were scanned using
      microcomputed tomography with a voxel size of 16.8 MUm before and after the
      retreatment procedures. To remove the filling material, the root canals were
      enlarged until the size 40, .04 taper instrument. The second step was to irrigate
      the root canals with xylene in the attempt to clean the root canals with paper
      points. In the third step, the passive ultrasonic irrigation technique (PUI) was
      performed using 2.5% sodium hypochlorite. The initial and residual filling
      material volume (mm(3) ) after each step was evaluated from the 0.5 to 6.5 mm
      level. The obtained data were expressed in terms of percentage of residual
      filling material. Statistical analysis was performed using the Friedman test (P <
      0.05). RESULTS: All specimens had residual filling materials after all
      retreatment procedures. Passive ultrasonic irrigation enhanced the elimination of
      residual filling material in comparison with the mechanical stage at the 0.5-2.5
      mm and 4.5-6.5 mm levels (P < 0.05). No significant difference was found between
      xylene and PUI methods. CONCLUSIONS: Filling materials were not completely
      removed by any of the retreatment procedures. The use of xylene and PUI after
      mechanical instrumentation enhanced removal of materials during endodontic
      retreatment of anatomically complex teeth.

PMID- 24456217
TI  - Achievement rates of Japan Atherosclerosis Society Guidelines 2007 LDL
      cholesterol goals with rosuvastatin or atorvastatin in patients who had not
      achieved their goal with atorvastatin.
AB  - BACKGROUND: The Japan Atherosclerosis Society's 2007 Guidelines for Prevention of
      Atherosclerotic Cardiovascular Diseases (JAS2007GL) advocate reducing LDL
      cholesterol (LDL-C) to target levels in patients with dyslipidemia, but
      achievement rates are frequently unsatisfactory even in the presence of lipid
      lowering therapy. This multicenter, open-label, randomized, parallel-group study
      compared the efficacy of rosuvastatin and atorvastatin on JAS2007GL LDL-C goals
      in Japanese patients not achieving their target goal with atorvastatin treatment.
      METHODS: The study involved 20 clinical institutes in Japan (Kishiwada
      Atherosclerosis Prevention Study [KAPS] Group). Patients with category II or III
      risk of coronary artery disease (CAD), or those with a history of CAD (secondary
      prevention), who had not achieved their JAS2007GL LDL-C goals during treatment
      with atorvastatin for at least 4 weeks were switched either to rosuvastatin 5
      mg/day (from atorvastatin 10 mg/day) or rosuvastatin 10 mg/day (from atorvastatin
      20 mg/day) (n = 75) or continued to receive atorvastatin (n = 77). The primary
      endpoint was achievement of LDL-C goals at 3 months. The main secondary endpoint
      was achievement of LDL-C goal + high-sensitivity C-reactive protein level <1.0
      mg/L at 3 months. RESULTS: Achievement rates for the primary endpoint were 49.3%
      in the rosuvastatin group and 31.7% in the atorvastatin group (P = 0.022).
      Achievement rates for the main secondary endpoint were 40.0% in the rosuvastatin
      group and 20.8% in the atorvastatin group (P = 0.010). Rosuvastatin and
      atorvastatin were both well tolerated in this study. CONCLUSIONS: Rosuvastatin is
      a useful treatment option for Japanese patients who are not achieving their
      JAS2007GL LDL-C goal with atorvastatin.

PMID- 24456218
TI  - A simple reconstruction of the posterior aspect of rhabdosphincter and sparing of
      puboprostatic collar reduces the time to early continence after laparoscopic
      radical prostatectomy.
AB  - BACKGROUND: Incontinence is a drawback after radical prostatectomy for prostate
      cancer. Several surgical methods to improve continence have been described
      however with contradictory results. OBJECTIVE: To determine whether a modified
      surgical technique during laparoscopic radical prostatectomy (LRP) improves
      postoperative continence. PATIENTS AND METHODS: This is a prospective
      nonrandomized study with two consecutive series of 100 patients in each group.
      The first group from 2005 to 2008 underwent a standard LRP. The second group from
      2009 to 2011 was subjected to a modified LRP by sparing of puboprostatic
      ligaments, including the preservation of arcus tendineous, and using a simple
      posterior tension-releasing suture adapting the urethra stump to the bladder
      before the anastomosis. The patients had the same preoperative work-up and
      comparable preoperative baseline characteristics. The 2-year follow-up of the
      patients included a continence questionnaire and International Prostate Symptom
      Score (IPSS). Urinary peak flow (Qmax) and post-void residual (PVR) volume were
      assessed at 3 months. Continence was defined as 0-1 pad/day. RESULTS: Only 99
      patients were evaluated in each group. The patients had comparable operative
      characteristics. The continence rates after the modified technique vs the
      standard were 33% vs 16%, p=0.007 at 1 month; 66% vs 44%, p=0.002 at 3 months;
      81% vs 67%, p=0.034 at 6 months; 92% vs 80%, p=0.024 at 12 months; and 95% vs
      86%, p=0.05 at 2 years. No significant differences were found regarding voiding
      functions, the Qmax, the PVR volume, or the IPSS. Three patients developed
      urethral stricture in the standard group compared with none in the modified
      group. The negative margin rates were unchanged. CONCLUSIONS: The anterior
      preservation and posterior suture technique studied is a simple, safe, and
      efficient method to shorten the time to continence after LRP without adverse
      effects on voiding or compromising the margin rates.

PMID- 24456219
TI  - High-efficiency solid phase peptide synthesis (HE-SPPS).
AB  - A series of improvements to the standard solid phase peptide synthesis (SPPS)
      process allowing for significant gains in product purity along with only a 4 min
      standard cycle time and a 90% reduction in total waste produced is reported. For
      example, syntheses of the well-known (65-74)acyl carrier protein (ACP) and (1
      42)beta-amyloid peptides were accomplished with 93 and 72% purity (UPLC-MS) in
      only 44 and 229 min, respectively. 

PMID- 24456220
TI  - Antenatal antioxidant treatment with melatonin to decrease newborn
      neurodevelopmental deficits and brain injury caused by fetal growth restriction.
AB  - Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication
      associated with increased rates of perinatal morbidity and mortality, and
      ultimately with long-term neurodevelopmental impairments. No intervention
      currently exists that can improve the structure and function of the IUGR brain
      before birth. Here, we investigated whether maternal antenatal melatonin
      administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant
      sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous
      infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were
      born naturally, neonatal behavioral assessment was used to examine neurological
      function and at 24 hr after birth the brain was collected for the examination of
      neuropathology. Compared to control lambs, IUGR lambs took significantly longer
      to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR
      brains showed widespread cellular and axonal lipid peroxidation, and white matter
      hypomyelination and axonal damage. Maternal melatonin administration ameliorated
      oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb
      brains, and IUGR + MLT lambs demonstrated significant functional improvements
      including a reduced time taken to attach to and suckle at the udder after birth.
      Based on these observations, we began a pilot clinical trial of oral melatonin
      administration to women with an IUGR fetus. Maternal melatonin was not associated
      with adverse maternal or fetal effects and it significantly reduced oxidative
      stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT
      placenta compared to IUGR alone. Melatonin should be considered for antenatal
      neuroprotective therapy in human IUGR.

PMID- 24456221
TI  - Role of prostaglandin D2 and CRTH2 blockade in early- and late-phase nasal
      responses.
AB  - BACKGROUND: Prostaglandin D2 (PGD2 ) plays an important role in allergic
      inflammation. The PGD2 receptor, CRTH2, is expressed on basophils, eosinophils,
      and Th2 lymphocytes and mediates chemotactic activity. OBJECTIVE: To define the
      role of CRTH2 in allergen-induced nasal responses in a mouse model of allergic
      rhinitis (AR), a potent, selective CRTH2 receptor antagonist, ARRY-063 was
      administered in a model of allergic rhinitis in mice. METHODS: ARRY-063 was
      administered orally to ovalbumin (OVA) sensitized and challenged mice. To assess
      nasal obstruction, respiratory frequency (RF) was monitored by whole-body
      plethysmography immediately after the 4th challenge (early-phase response, EPR)
      and 24 h after the 6th challenge (late-phase response, LPR). Nasal resistance
      (RNA ) was also measured in the LPR. PGD2 was administered with or without OVA to
      determine the effect of PGD2 on nasal responsiveness. Cytokine levels and
      histopathological changes in nasal tissue were analysed. RESULTS: Instillation of
      PGD2 in the nose of sensitized mice together with a low concentration of OVA
      induced both an EPR and LPR. Treatment with the CRTH2 receptor antagonist
      prevented the decreases in RF seen immediately following the 4th challenge of
      sensitized mice (EPR). In the LPR, decreases in RF and increases in RNA were also
      prevented by antagonist treatment associated with reduced cytokine levels and
      inflammation in nasal tissues. CONCLUSIONS: These data identify PGD2 as a
      mediator of both the EPR and LPR in this model of AR and suggest that antagonism
      of CRTH2 prevents the development of both the EPR and LPR as well as nasal
      inflammation.

PMID- 24456222
TI  - Self-rated mental health in socio-structural contexts: an examination with Korean
      American older adults.
AB  - OBJECTIVES: Following the socio-structural framework of health, the study
      examined the role of social/interpersonal and environmental/neighborhood factors
      in predicting self-rated mental health (SRMH) in Korean American older adults.
      METHOD: Using the survey data from 420 older Korean Americans (mean age = 71.6,
      SD = 7.59), multivariate models of SRMH was estimated with sets of predictors:
      (1) background information (demographic characteristics and chronic conditions),
      (2) mental health symptom measures (depressive symptoms and anxiety), (3)
      social/interpersonal factors (social network and filial satisfaction), and (4)
      environmental/neighborhood factors (neighborhood safety and residential
      satisfaction). RESULTS: Social/interpersonal and environmental/neighborhood
      factors were found to make a significant contribution to the predictive model
      even after controlling for background information and mental health symptom
      measures. Those with higher levels of filial satisfaction and more favorable
      perceptions of neighborhood safety were likely to have positive ratings of SRMH.
      CONCLUSION: Findings supported the importance of considering socio-structural
      contexts in the assessment of SRMH and provided implications for mental health
      services for the target population.

PMID- 24456223
TI  - Has carotid artery stenting found its place? A 10-year regional centre
      perspective.
AB  - INTRODUCTION: The post-Carotid Revascularization Endarterectomy versus Stenting
      Trial era has seen a dramatic decline in the practice of carotid artery stenting
      (CAS). A retrospective review of prospectively collected CAS outcomes over a 10
      year period by a single operator was undertaken to determine if this change in
      practice is justified and to identify the place of carotid stenting in current
      practice. METHODS: One hundred fifty-nine carotid stent procedures were
      undertaken on 137 patients from 2002 to 2012. Cases were selected for CAS only if
      they fulfilled the inclusion criteria for the SAPPHIRE trial. Post-procedural
      outcomes were compared against those of a contemporaneous cohort of patients
      undergoing carotid endarterectomy (CEA) by the same operator and against
      published meta-analyses. The measure of CAS durability was need for re
      intervention, based on the presence of ultrasound-detected re-stenosis >70%.
      RESULTS: No significant difference was identified in 30-days' complication rates
      between patients undergoing CAS and those having CEA. Compared to published meta
      analyses of CAS, our practice was accompanied by a significantly lower rate of
      peri-procedural stroke (1.26% versus 6%, P = 0.014) while carrying equivalent 30
      days' death and myocardial infarction. Four stented arteries had re-intervention,
      due to asymptomatic in-stent stenosis of >70%. Further intervention was declined
      in a fifth case. This represents a re-stenosis rate of 3.1% over a mean follow-up
      of 40.2 +/- 27.6 months. DISCUSSION: CAS can provide a safe and durable treatment
      option for selected patients with carotid artery disease, in the hands of
      appropriately trained proceduralists who meet accepted standards of practice.

PMID- 24456225
TI  - Frugivores and cheap fruits make fruiting fruitful.
AB  - Animal seed dispersal provides an important ecosystem service by strongly
      benefiting plant communities. There are several theoretical studies on the
      ecology of plant-animal seed-disperser interactions, but few studies have
      explored the evolution of this mutualism. Moreover, these studies ignore plant
      life history and frugivore foraging behaviour. Thus, it remains an open question
      what the conditions for the diversification of fruit traits are, in spite of the
      multitude of empirical studies on fruit trait diversity. Here, we study the
      evolution of fruit traits using a spatially explicit individual-based model,
      which considers the costs associated with adaptations inducing dispersal by
      frugivory, as well as frugivore foraging behaviour and abundance. Our model
      predicts that these costs are the main determinants of the evolution of fruit
      traits and that when the costs are not very high, the evolution of larger fruit
      traits (e.g. fleshy/colourful fruits) is controlled by the choosiness and
      response thresholds of the frugivores as well as their numerical abundance. 

PMID- 24456224
TI  - Peroxisome proliferator-activated receptor gamma agonists in the prevention and
      treatment of murine systemic lupus erythematosus.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists are known
      to have many immunomodulatory effects. We have previously shown that the
      PPARgamma agonist rosiglitazone is beneficial when used early in prevention of
      disease in murine models of systemic lupus erythematosus (SLE) and SLE-related
      atherosclerosis. In this report, we demonstrate that another PPARgamma agonist,
      pioglitazone is also beneficial as a treatment for early murine lupus, indicating
      that this is a class effect and not agent-specific. We further attempt to define
      the ability of PPARgamma agonists to ameliorate established or severe autoimmune
      disease using two mouse models: the MRL.lpr SLE model and the gld.apoE(-/-) model
      of accelerated atherosclerosis and SLE. We demonstrate that, in contrast to the
      marked amelioration of disease seen when PPARgamma agonist treatment was started
      before disease onset, treatment with rosiglitazone after disease onset in MRL.lpr
      or gld.apoE(-/-) mice had minimal beneficial effect on the development of the
      autoimmune phenotype; however, rosiglitazone treatment remained highly effective
      at reducing lupus-associated atherosclerosis in gld.apoE(-/-) mice after disease
      onset or when mice were maintained on a high cholesterol Western diet. These
      results suggest that beneficial effects of PPARgamma agonists on the development
      of autoimmunity might be limited to the early stages of disease, but that
      atherosclerosis, a major cause of death in SLE patients, may be ameliorated even
      in established or severe disease. 

PMID- 24456226
TI  - Causes of male sexual trait divergence in introduced populations of guppies.
AB  - Males from different populations of the same species often differ in their
      sexually selected traits. Variation in sexually selected traits can be attributed
      to sexual selection if phenotypic divergence matches the direction of sexual
      selection gradients among populations. However, phenotypic divergence of sexually
      selected traits may also be influenced by other factors, such as natural
      selection and genetic constraints. Here, we document differences in male sexual
      traits among six introduced Australian populations of guppies and untangle the
      forces driving divergence in these sexually selected traits. Using an
      experimental approach, we found that male size, area of orange coloration, number
      of sperm per ejaculate and linear sexual selection gradients for male traits
      differed among populations. Within populations, a large mismatch between the
      direction of selection and male traits suggests that constraints may be important
      in preventing male traits from evolving in the direction of selection. Among
      populations, however, variation in sexual selection explained more than half of
      the differences in trait variation, suggesting that, despite within-population
      constraints, sexual selection has contributed to population divergence of male
      traits. Differences in sexual traits were also associated with predation risk and
      neutral genetic distance. Our study highlights the importance of sexual selection
      in trait divergence in introduced populations, despite the presence of
      constraining factors such as predation risk and evolutionary history. 

PMID- 24456227
TI  - A copper-catalyzed domino route toward purine-fused tricyclic derivatives.
AB  - Purine-fused tricyclic derivatives have been synthesized via a copper-catalyzed
      domino Michael/oxidative cross-coupling reaction between adenines and
      nitroolefins for the first time. With air as the oxidant, this method has high
      regioselectivity, which provides a new route for constructing purine-nucleoside
      conjugated systems with two newly formed C-N bonds. Meanwhile, purine nucleosides
      with an exocyclic amino group could be obtained easily by simple reduction, which
      may lead to potential applications in fluorescence recognition of various bases
      in vivo.

PMID- 24456228
TI  - False positivity of gamma-glutamyl transpeptidase measurement in urine.
AB  - Although enzymuria tends to be associated to renal injury, there are no studies
      that have evaluated the presence of the enzyme gamma-glutamyl transpeptidase
      (GGT) spectrophotometry in the urine using a non-nephrotoxic agent (Nerium
      oleander) in order to evaluate the possibility of false positive results. The
      urinary GGT/urinary creatinine concentration ratio (uGGT/uCr) of 10 healthy dogs
      was calculated and posteriorly confronted with data from clinical evaluation,
      hematological and serum biochemical profiles, creatinine clearance (CrC),
      urinalysis, urine protein/creatinine ratio (UPC), electrocardiogram, systemic
      blood pressure (SBP) and light and electron microscopy. The results for kidney
      histology, SBP, UPC and CrC were not significantly different in any of the time
      points analyzed. However, uGGT/uCr was significantly higher when measured 4 hours
      and 24 hours after administration of N. oleander. The measurement of the urinary
      GGT enzyme, as performed in many studies, yielded false positive results in dogs
      poisoned by a non-nephrotoxic agent.

PMID- 24456229
TI  - Factors influencing recruitment to research: qualitative study of the experiences
      and perceptions of research teams.
AB  - BACKGROUND: Recruiting the required number of participants is vital to the
      success of clinical research and yet many studies fail to achieve their expected
      recruitment rate. Increasing research participation is a key agenda within the
      NHS and elsewhere, but the optimal methods of improving recruitment to clinical
      research remain elusive. The aim of this study was to identify the factors that
      researchers perceive as influential in the recruitment of participants to
      clinically focused research. METHODS: Semi-structured interviews were conducted
      with 11 individuals from three clinical research teams based in London. Sampling
      was a combination of convenience and purposive. The interviews were audio
      recorded, transcribed verbatim and analysed using the framework method to
      identify key themes. RESULTS: Four themes were identified as influential to
      recruitment: infrastructure, nature of the research, recruiter characteristics
      and participant characteristics. The main reason individuals participate in
      clinical research was believed to be altruism, while logistical issues were
      considered important for those who declined. Suggestions to improve recruitment
      included reducing participant burden, providing support for individuals who do
      not speak English, and forming collaborations with primary care to improve the
      identification of, and access to, potentially eligible participants. CONCLUSIONS:
      Recruiting the target number of research participants was perceived as difficult,
      especially for clinical trials. New and diverse strategies to ensure that all
      potentially eligible patients are invited to participate may be beneficial and
      require further exploration in different settings. Establishing integrated
      clinical and academic teams with shared responsibilities for recruitment may also
      facilitate this process. Language barriers and long journey times were considered
      negative influences to recruitment; although more prominent, these issues are not
      unique to London and are likely to be important influences in other locations.

PMID- 24456230
TI  - Impact of the 2009 influenza A H1N1 pandemic on invasive pneumococcal disease in
      adults.
AB  - BACKGROUND: The incidence of invasive pneumococcal disease (IPD) appears to be
      associated with influenza. The objectives of this study were to evaluate the
      changes in IPD incidence and clinical data as well as the trends in Streptococcus
      pneumoniae serotype distribution in adults during the peak period of the 2009
      influenza A H1N1 pandemic (IAP). METHODS: We performed a prospective multicentre
      study on IPD from week 42 to 48, 2009 in an area of Barcelona (Catalonia, Spain)
      covering 1,483,781 adult inhabitants. Serotyping was done by Quellung reaction.
      The data from 2009 were compared to those from the same periods in 2008 and 2010.
      RESULTS: Two hundred and three cases of IPD were detected during 2009, compared
      with 182 in 2008 and 139 in 2010. The incidence of IPD during the 7-week study
      period in 2009 (2.89) was statistically higher than that observed in 2008 (1.96)
      and 2010 (1.46). IAP was confirmed in 3/30 patients during the 2009 study period.
      Patients with IPD in 2009 were significantly healthier and younger than those in
      the other years, although the mortality was higher than in 2008 (p = 0.05) and
      2010 (p > 0.05). Eleven (10 non-PCV-7) serotypes not present in 2008 appeared in
      2009. CONCLUSIONS: During weeks 42 to 48, in which the 2009 IAP peaked in
      Catalonia, the incidence of IPD was statistically higher than that observed in
      the same time period in 2008 and 2010, with some differences in the
      epidemiological data, showing a close relationship between S. pneumoniae and
      influenza.

PMID- 24456231
TI  - Distribution and origin of groundwater methane in the Wattenberg oil and gas
      field of northern Colorado.
AB  - Public concerns over potential environmental contamination associated with oil
      and gas well drilling and fracturing in the Wattenberg field in northeast
      Colorado are increasing. One of the issues of concern is the migration of oil,
      gas, or produced water to a groundwater aquifer resulting in contamination of
      drinking water. Since methane is the major component of natural gas and it can be
      dissolved and transported with groundwater, stray gas in aquifers has elicited
      attention. The initial step toward understanding the environmental impacts of oil
      and gas activities, such as well drilling and fracturing, is to determine the
      occurrence, where it is and where it came from. In this study, groundwater
      methane data that has been collected in response to a relatively new regulation
      in Colorado is analyzed. Dissolved methane was detected in 78% of groundwater
      wells with an average concentration of 4.0 mg/L and a range of 0-37.1 mg/L.
      Greater than 95% of the methane found in groundwater wells was classified as
      having a microbial origin, and there was minimal overlap between the C and H
      isotopic characterization of the produced gas and dissolved methane measured in
      the aquifer. Neither density of oil/gas wells nor distance to oil/gas wells had a
      significant impact on methane concentration suggesting other important factors
      were influencing methane generation and distribution. Thermogenic methane was
      detected in two aquifer wells indicating a potential contamination pathway from
      the producing formation, but microbial-origin gas was by far the predominant
      source of dissolved methane in the Wattenberg field. 

PMID- 24456232
TI  - Significantly enhancing supercapacitive performance of nitrogen-doped graphene
      nanosheet electrodes by phosphoric acid activation.
AB  - In this work, we present a new method to synthesize the phosphorus, nitrogen
      contained graphene nanosheets, which uses dicyandiamide to prevent the
      aggregation of graphene oxide and act as the nitrogen precursor, and phosphoric
      acid (H3PO4) as the activation reagent. We have found that through the H3PO4
      activation, the samples exhibit the remarkably enhanced supercapacitive
      performance, and depending on the amount of H3PO4 introduced, the specific
      capacitance of the samples is gradually increased from 7.6 to 244.6 F g(-1).
      Meanwhile, the samples also exhibit the good rate capability and excellent
      stability (up to 10 000 cycles). Through the transmission electron microscopy,
      high-resolution transmission electron microscopy, X-ray diffraction, X-ray
      photoelectron spectroscopy and Brunauer-Emmett-Teller analyses, H3PO4 treatment
      induced large pore volume and phosphorus related function groups in the product
      are assumed to response for the enhancement. 

PMID- 24456233
TI  - Mechanism of the malabaricone C-induced toxicity to the MCF-7 cell line.
AB  - In this study, we studied the mechanism of the cytotoxicity of malabaricone C
      (mal C) against human breast cancer MCF-7 cell line. Mal C dose-dependently
      increased the sub G1 cell population, associated with cytoplasmic oligonucleosome
      formation and chromatin condensation. The mal C-induced apoptosis led to
      mitochondrial damage as revealed by fluorescence microscopy and flow cytometry of
      the JC-1-stained cells as well as from the release of mitochondrion-specific
      nuclease proteins AIF and endo G. Mal C also released intracellular Ca(2+) from
      the MCF-7 cells, but the Ca(2+)-modulators BAPTA-AM and Ru360 only partially
      abrogated the apoptosis. The calpain activation by mal C did not have any effect
      on its cytotoxicity. On the other hand, after mal C treatment significant
      lysosomal membrane permeabilization (LMP), along with release of cathepsin B, as
      well as Bid-cleavage and its translocation to mitochondria were observed much
      earlier than the mitochondrial damage. This suggested that cytotoxicity of mal C
      against human MCF-7 human breast cancer cell line may proceed through LMP as the
      initial event that triggered a caspase-independent, but cathepsin B and t-Bid
      dependent intrinsic mitochondrial apoptotic pathway. A significant accumulation
      of cells in the S or G2-M phases along with upregulation of the cyclins E and A
      due to mal C exposure promises it to be a potential anti-cancer agent.

PMID- 24456234
TI  - Urea induced unfolding dynamics of flavin adenine dinucleotide (FAD):
      spectroscopic and molecular dynamics simulation studies from femto-second to
      nanosecond regime.
AB  - Here, we investigate the effect of urea in the unfolding dynamics of flavin
      adenine dinucleotide (FAD), an important enzymatic cofactor, through steady
      state, time-resolved fluorescence spectroscopic and molecular dynamics (MD)
      simulation studies. Steady state results indicate the possibility of urea induced
      unfolding of FAD, inferred from increasing emission intensity of FAD with urea.
      The TCSPC and up-conversion results suggest that the stack-unstack dynamics of
      FAD severely gets affected in the presence of urea and leads to an increase in
      the unstack conformation population from 15% in pure water to 40% in 12 M urea.
      Molecular dynamics simulation was employed to understand the nature of the
      interaction between FAD and urea at the molecular level. Results depict that urea
      molecules replace many of the water molecules around adenine and isoalloxazine
      rings of FAD. However, the major driving force for the stability of this unstack
      conformations arises from the favorable stacking interaction of a significant
      fraction of the urea molecules with adenine and isoalloxazine rings of FAD, which
      overcomes the intramolecular stacking interaction between themselves observed in
      pure water. 

PMID- 24456235
TI  - Energy crops for biofuel feedstocks: facts and recent patents on genetic
      manipulation to improve biofuel crops.
AB  - Burning fossil-fuels to meet the global energy requirements by human being has
      intensified the concerns of increasing concentrations of greenhouse gases.
      Therefore, serious efforts are required to develop nonfossil-based renewable
      energy sources. Plants are more efficient in utilizing solar energy to convert it
      into biomass which can be used as feedstocks for biofuel production. Hence with
      the increasing demands of energy and the needs of cost-effective, sustainable
      production of fuels, it has become necessary to switch over to plant biomass as a
      renewable source of energy. Biofuels derived from more sustainable biological
      materials such as lignocellulosic plant residues, considered as second generation
      biofuels, are more dependable. However, there are technical challenges such as
      pretreatment and hydrolysis of lignocellulosic biomass to convert it into
      fermentable sugars. Plant genetic engineering has already proven its potential in
      modifying cell wall composition of plants for enhancing the efficiency of biofuel
      production. Interest and potential in the area are very much evident from the
      growing number of patents in the recent years on the subject. In this review,
      recent trends in genetic engineering of energy crops for biofuel production have
      been introduced, and strategies for the future developments have been discussed. 

PMID- 24456236
TI  - Bicyclic hybrid sugars as glycosidase inhibitors: synthesis and comparative study
      of inhibitory activities of fused oxa-oxa, oxa-aza, and oxa-carbasugar hybrid
      molecules.
AB  - A few bicyclic hybrid sugar molecules comprising of oxa-aza, oxa-oxa, and oxa
      carbasugar fused skeletons were designed and synthesized from C-2 acetoxyglucal
      involving Ferrier rearrangement, Grignard addition, and ring-closing metathesis
      as key steps. The inhibitory activities of the synthesized molecules were tested
      against commercially available enzymes, which revealed the sugar-piperidine and
      sugar-pyran hybrids as potent and selective inhibitors. 

PMID- 24456237
TI  - Food additive carrageenan: Part I: A critical review of carrageenan in vitro
      studies, potential pitfalls, and implications for human health and safety.
AB  - Carrageenan (CGN) has been used as a safe food additive for several decades.
      Confusion over nomenclature, basic CGN chemistry, type of CGN tested,
      interspecies biology, and misinterpretation of both in vivo and in vitro data has
      resulted in the dissemination of incorrect information regarding the human safety
      of CGN. The issue is exacerbated when mechanistic data obtained from in vitro
      experiments are directly translated to human hazard and used for risk assessment.
      This can lead to information that is taken out of experimental context and
      reported as a definitive effect in humans. In recent years, the use of cell-based
      models has increased and their ability to provide key information regarding
      chemical or drug safety is well established. In many instances, these new
      alternative approaches have started to replace the need to use animals
      altogether. In vitro systems can be extremely useful for understanding
      subcellular targets and mechanisms of adverse effects. However, care must be
      exercised when extrapolating the in vitro findings to in vivo effects. Often,
      issues such as chemical identity and purity, relevant dose, pharmacokinetic
      properties, solubility, protein binding, adsorption to plastics, and the use of
      cell models that are biologically and mechanistically relevant are overlooked or
      ignored. When this occurs, in vitro findings can provide misleading information
      that is not causally linked to in vivo events in animals or in humans. To date,
      there has not been a comprehensive review of the CGN in vitro literature, which
      has reported a wide range of biochemical effects related to this compound. An
      extensive effort has been made to evaluate as much of this literature as
      possible. This review focuses on the in vitro observation, the unique chemistry
      of CGN, and potential pitfalls of in vitro models used for hazard identification.
      The discussion of the in vitro studies discussed this review are supported by
      numerous in vivo studies. This provides a unique opportunity to have both the in
      vitro and in vivo studies reviewed together.

PMID- 24456239
TI  - Tubeless percutaneous nephrolithotomy using antegrade tether: a randomized study.
AB  - BACKGROUND AND PURPOSE: Tubeless percutaneous nephrolithotoomy (PCNL), although
      an accepted technique by now, continues to suffer from two major limitations: The
      need for postoperative cystoscopy for ureteral stent removal and inability to
      perform a "second-look" procedure for any residual fragments. We share our
      experience with a modification of the standard tubeless PCNL technique that
      allows us to overcome these shortcomings. PATIENTS AND METHODS: A total of 166
      patients selected to have PCNL were randomized into two groups of 83 each. In
      group A (control group), the patients underwent standard PCNL with the insertion
      of a nephrostomy tube at completion; in group B (intervention group), modified
      tubeless PCNL was performed with a Double-J (DJ) stent inserted with a tether
      attached to its proximal end, taken out through the percutaneous tract. The
      nephrostomy tube in group A was removed postoperatively on the second or third
      day, whereas those in group B had the stent removed directly by pulling the
      attached tether within the office setting 10 to 14 days postoperatively. RESULTS:
      The need for postoperative analgesia was significantly higher in group A compared
      with group B (mean dose of tramadol needed, 128 mg vs 81.3 mg) (P<0.001). Four
      patients in group A had postoperative urinary leakage from the nephrostomy site,
      whereas there were no leaks in patients in group B. Group B patients spent
      significantly shorter average time in hospital (21.6 hours) compared with group A
      (54 hours) (P<0.001). Two of the patients in group B needed a second-look
      procedure, performed by the insertion of a guidewire down the stent, which was
      pulled out partially by its tether. Presence of the tether in the flank or the
      process of subsequent removal did not cause any discomfort to any patient.
      CONCLUSION: The present study demonstrates that tubeless PCNL with a tethered DJ
      stent overcomes its main drawback, namely, the need for cystoscopy for stent
      removal, and also allows access to the pelvicaliceal system for second-look
      nephroscopy.

PMID- 24456240
TI  - Positive sentinel lymph node metastasis from a metastasis in Melanoma.
AB  - The rationale for certain patterns of metastatic spread seen in melanoma is not
      well understood. Currently, there is no clear experimental evidence to support
      the potential for metastases to form metastases in this disease. We report a case
      of a 31-year-old woman, with metastatic melanoma, who developed axillary lymph
      node metastases hypothesized to originate from a breast metastasis rather than
      the primary disease. Improved understanding of the underlying molecular processes
      involved in systemic spread would facilitate development of improved adjuvant
      therapies and prognostic markers. 

PMID- 24456241
TI  - Gold(I)/(III)-catalyzed rearrangement of divinyl ketones and
      acyloxyalkynyloxiranes into cyclopentenones.
AB  - Multifaceted gold(I/III) catalysts with their carbophilic and oxophilic
      characters catalyzed very efficiently the formation of hydroxylated
      cyclopentenones from simple divinyl ketones or acyloxyalkynyloxiranes. The
      Nazarov reaction is rapidly performed in dichloroethane with 5 mol % of the
      simple gold(III) trichloride salt at 70  degrees C, while the rearrangement of
      alkynyloxiranes requires 5 mol % of a more stable NHC gold(III) triflimidate
      complex. 

PMID- 24456243
TI  - Pacing or ablation: which is better for paroxysmal atrial fibrillation-related
      tachycardia-bradycardia syndrome?
AB  - BACKGROUND: Symptomatic prolonged sinus pauses on termination of atrial
      fibrillation (AF) are an accepted indication for pacemaker implantation. We
      evaluated the outcome of AF ablation in patients with paroxysmal AF-related
      tachycardia-bradycardia syndrome and compared the efficacy of catheter ablation
      with permanent pacing plus antiarrhythmic drugs (AADs). METHODS AND RESULTS:
      Patients with prolonged symptomatic sinus pauses on termination of AF were
      retrospectively analyzed. Forty-three consecutive patients who underwent catheter
      ablation (ABL group) were compared to 57 patients who underwent permanent pacing
      plus AADs (PM group). All 43 patients in the ABL group fulfilled Class I
      indication for pacemaker implantation at baseline but they actually underwent AF
      ablation. Reevaluation after 20.1 +/- 9.6 months of follow-up showed that 41
      patients (95.3%) did no longer need a pacemaker (Class III indication). Total
      cardiac-related rehospitalization was not significantly different between the two
      groups (P = 0.921). Tachycardia-related hospitalization was significantly higher
      in the PM group than the ABL group (14.0% and 0%, P = 0.029). More patients in
      the PM group were on AADs (PM 40.4%, ABL 4.7%, P < 0.001) while sinus rhythm
      maintenance was remarkably higher in the ABL group at the end of follow-up (83.7%
      vs 21.1% in PM group, P < 0.001). CONCLUSIONS: In patients with paroxysmal AF
      related tachycardia-bradycardia syndrome, AF ablation seems to be superior to a
      strategy of pacing plus AAD. Pacemaker implantation can be waived in the majority
      of patients after a successful ablation.

PMID- 24456244
TI  - Late-onset Pneumocystis jirovecii pneumonia in solid organ transplant recipients.
AB  - Anti-Pneumocystis prophylaxis is recommended for at least 6-12 months after solid
      organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP)
      occur during the first year post transplantation. Herein, we report 4 cases of
      late-onset PCP (>1 year post transplant). PCP appeared in a range of 50-68 months
      post transplant. Two cases had history of humoral rejection episodes treated with
      rituximab, and the other 2 had low CD4+ T-cell count (<200 cells/mm(3) ) at the
      time of diagnosis. All 4 patients survived. In conclusion, although the number of
      cases is low, we must be aware of the possibility of late-onset PCP in solid
      organ transplant patients. The role of previous use of rituximab or persistent
      CD4+ T-cell lymphopenia should be addressed in future studies.

PMID- 24456245
TI  - Design, synthesis, and biological evaluation of deuterated C-aryl glycoside as a
      potent and long-acting renal sodium-dependent glucose cotransporter 2 inhibitor
      for the treatment of type 2 diabetes.
AB  - SGLT2 inhibitors deuterated at sites susceptible to oxidative metabolism were
      found to have a slightly longer tmax and half-life (t1/2), dose-dependent
      increase in urinary glucose excretion (UGE) in rats, and slightly superior
      effects on UGE in dogs while retaining similar in vitro inhibitory activities
      against hSGLT2. In particular, deuterated compound 41 has the potential to be a
      robust long-acting antidiabetic agent. 

PMID- 24456246
TI  - Four new triterpenoid glycosides from the seed residue of Hippophae rhamnoides
      subsp. sinensis.
AB  - Four new triterpenoid saponins (1-4) were isolated from the seed residue of
      Hippophae rhamnoides subsp. sinensis, named 3-O-[beta-D-glucopyranosyl(1 -> 2)
      beta-D-glucopyranosyl-(1 -> 3)]-[alpha-L-rhamnopyranosyl-(1 -> 2)]-alpha-L
      arabinopyranosyl-13-ene-19-one-28-oic acid 28-O-beta-D-glucopyranosyl ester (1),
      3-O-[beta-D-glucopyranosyl(1 -> 2)-beta-D-glucopyranosyl-(1 -> 3)]-[alpha-L
      rhamnopyranosyl-(1 -> 2)]-alpha-L-arabinopyranosyl-13-ene-19-one-30-hydroxyolean
      28-oic acid 28-O-beta-D-glucopyranosyl ester (2), 3-O-[beta-D-glucopyranosyl(1 ->
      2)-beta-D-glucopyranosyl-(1 -> 3)]-[alpha-L-rhamnopyranosyl-(1 -> 2)]-beta-D
      glucopyranosyl-13-ene-19-one-28-oic acid 28-O-beta-D-glucopyranosyl ester (3),
      and 3-O-[beta-D-glucopyranosyl(1 -> 2)-beta-D-glucopyranosyl-(1 -> 3)]-[alpha-L
      rhamnopyranosyl-(1 -> 2)]-beta-D-glucopyranosyl-13-ene-19-one-30-hydroxyolean-28
      oic acid 28-O-beta-D-glucopyranosyl ester (4), and their structures were
      elucidated on the basis of spectroscopic and chemical methods.

PMID- 24456247
TI  - New oleanane-type triterpenoid saponins isolated from the seeds of Celosia
      argentea.
AB  - Three new oleanane-type triterpenoid saponins named celosins H, I, and J were
      isolated from the seeds of Celosia argentea L. Their structures were
      characterized as 3-O-beta-D-xylopyranosyl-(1 -> 3)-beta-D-glucuronopyranosyl
      polygalagenin 28-O-beta-D-glucopyranosyl ester, 3-O-beta-D-glucuronopyranosyl
      medicagenic acid 28-O-beta-D-xylcopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl-(1 
      > 2)-beta-D-fucopyranosyl ester, and 3-O-beta-D-glucuronopyranosyl-medicagenic
      acid 28-O-alpha-L-arabinopyranosyl-(1 -> 3)-[beta-D-xylcopyranosyl-(1 -> 4)]
      alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-fucopyranosyl ester by NMR, MS, and
      chemical evidences, respectively. In our opinion, celosins H-J could be used as
      chemical markers for the quality control of C. argentea seeds.

PMID- 24456249
TI  - Two new oligostilbenes from the stem of Parthenocissus quinquefolia.
AB  - Two new oligostilbenes, parthenocissins M (1) and N (2), together with two known
      compounds, miyabenol C (3) and epsilon-viniferin (4), were isolated from the stem
      of Parthenocissus quinquefolia. Their structures were elucidated by means of NMR,
      UV, IR, and MS data. 

PMID- 24456248
TI  - Two new bisabolane sesquiterpenoids from Curcuma longa.
AB  - Two new bisabolane derivatives were isolated from the rhizome of Curcuma longa
      L., and their structures were characterized by analyzing spectroscopic data
      especially 1D- and 2D-NMR spectra. Relative configurations of two compounds were
      determined by NOESY correlations. 

PMID- 24456250
TI  - Two new indole-diterpenoids from the fungus Penicilliumcrustosum YN-HT-15.
AB  - Two new indole-diterpenoids named penijanthine B and penitrem H were isolated
      from the metabolites of the fungus Penicilliumcrustosum YN-HT-15, which was
      isolated from the red soil of Yunnan Province of China. The structures were
      determined on spectroscopic analyses and CD spectra.

PMID- 24456251
TI  - Microbial transformation of resibufogenin by Curvularia lunata AS 3.4381.
AB  - In this paper, the microbial transformation of resibufogenin by Curvularia lunata
      AS 3.4381 was investigated, and four transformed products were isolated and
      characterized as 3-epi-resibufogenin (2), 12alpha-hydroxy-3-epi-resibufogenin
      (3), 12-oxo-16beta-hydroxy-3-epi-resibufogenin (4), and 12beta,15-epoxy-3-epi
      bufalin-14,15-ene (5). Among them, 4 and 5 are new compounds, and isomerization,
      hydroxylation, and oxidation reactions in microbial transformation process were
      observed. Additionally, the cytotoxicities of transformed products (2-5) were
      also investigated.

PMID- 24456252
TI  - Synthesis and cytotoxic activities of a series of novel N-methyl
      bisindolylmaleimide amide derivatives.
AB  - A novel series of N-methyl-bisindolylmaleimides were synthesized and evaluated
      for their inhibitory activities against nine tumor cell lines. Some of the
      compounds showed an interesting activity against the tested cell lines. The most
      potent compounds 5e and 5j displayed antiproliferative activity with 50%
      inhibitory concentration values in the MUM range against some tested cell lines. 

PMID- 24456253
TI  - Synthesis and antifungal activity of 7-methyl-7-hydroxy-2,3-benzo[c]octa-1,6
      olide.
AB  - The racemic 7-methyl-7-hydroxy-2,3-benzo[c]octa-1,6-olide, the analog of natural
      product (6R)-3,7-dimethyl-7-hydroxy-2-octen-1,6-olide, was totally synthesized
      using easily available (E)-2-(2-carboxyvinyl)benzoic acid as a raw material in
      nine-step reactions including three key steps of Wittig reaction, epoxidation,
      and cyclization, with an overall yield of 10.3%. The bioassay results showed that
      ( +/- )-2 exhibited stronger antifungal activity than the natural product ( +/- )
      1 and (R)-1 against Alternaria solani with an EC50 value of 27.36 MUg/ml.

PMID- 24456254
TI  - A new dihydroagarofuranoid sesquiterpene from the roots of Tripterygium
      hypoglaucum.
AB  - A new sesquiterpene ester (1) has been isolated from the root bark of
      Tripterygium hypoglaucum. The structure was determined as 1alpha-acetoxy
      6beta,9beta-dibenzoyloxy-4beta-hydroxy-dihydroagarofuran by the extensive
      analysis of NMR data, and the absolute configurations were established as 1R, 4R,
      6S, and 9R by application of the CD excitation chirality method. Compound 1
      exhibited weak cytotoxicity against HeLa cells, with an IC50 value of 30.2 MUM.

PMID- 24456255
TI  - Hypertonic HBOC-201 decreases neutrophil activation after hemorrhagic shock.
AB  - OBJECTIVE: To evaluate neutrophil activation after exposure to standard HBC-201
      (suspended in lactate Ringer's solution) versus HBOC-201 suspended in hypertonic
      7.5% saline solution. METHODS: We use plasma and tissue obtained from pigs
      subjected to controlled hemorrhagic shock and an ex vivo model of stimulated
      human whole blood. The pigs were resuscitated with the following (n = 8 per
      group) standard HBOC-201, or hypertonic HBOC-201. We used HTS 7.5%, Ringer's
      lactate as control resuscitation. Human blood was stimulated with same fluids. We
      measured the following neutrophil markers; IL-8, H2O2 in pig plasma, MPO in pig
      tissue, and H2O2, IL-8, and CD11b/CD18 in human whole blood. RESULTS: H2O2 and IL
      8 as well as tissue MPO were significantly decreased in pigs resuscitated with HT
      HBOC-201 and HT 7.5%. Ex vivo experiments blood diluted with HTS and HT-HBOC-201
      revealed lower expression of CD11b/CD18, H2O2, and IL-8. Blood diluted with HBOC
      201 had a higher CD11b/CD18 expression than blood diluted with LR solution.
      CONCLUSION: Our in vivo and ex vivo experiments indicate that HBOC-201 suspended
      in hypertonic 7.5% saline solution is associated with significantly less
      neutrophil activation when compared to standard HBOC-201 suspended in lactate
      Ringer's solution.

PMID- 24456256
TI  - Retracted: Nurses learning in the workplace: a comparison of workplace attributes
      in acute care settings in Australia and Singapore.
AB  - BACKGROUND: Workplaces need to foster teaching and learning interactions so staff
      collaborate and learn from each other. Internationally, many countries provide
      support to graduates and experienced staff to foster engagement necessary for
      learning and quality care. Workplace attributes can differ across countries
      depending on managerial, contextual, social and policy issues. AIM: This study
      compared workplace attributes of two Australian hospitals with a Singaporean
      hospital. METHODS: A representative sample of nurses in two acute care facilities
      in Australia (n = 203) and a comparable facility in Singapore (n = 154) during
      2010 and 2011 responded to a survey requesting demographic data and responses
      about workplace attributes. Attributes were determined through validated tools
      that measure staff perception of support when facilitating others learning
      (Support Instrument for Nurses Facilitating the Learning of Others) and the
      clinical learning organizational culture (Clinical Learning Organizational
      Culture Survey). RESULTS: Results indicated Singaporean nurses rated perception
      of acknowledgement, workload management and teamwork support in facilitating
      learners in their hospital as significantly better than the Australian cohort
      despite similar provisions for support and development. There were no significant
      differences across the two sites in the clinical learning culture. LIMITATIONS:
      Analysis across three health facilities only provides a snapshot. Targeting more
      facilities would assist in confirming the extent of reported trends. CONCLUSIONS:
      Findings indicate differences in nurses' perceptions of support when facilitating
      learners. Further exploration of Singaporean nurses' increased perceptions of
      support is worthy. Clinical learning organizational culture findings across
      Australian and Singaporean acute care facilities suggest common attributes within
      the nursing profession that transcend contextual factors, for example, a strong
      sense of task accomplishment. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurses
      across both countries demonstrate strengths in accomplishing tasks but less so in
      recognizing nurses' contributions that may also impact nurses' influence in the
      practice context. As these attributes are common, nursing can collectively lobby
      and develop policy, thereby strengthening their cause to be recognized.

PMID- 24456257
TI  - Intravenous human immunoglobulin treatment of serum from HLA-sensitized patients
      in kidney transplantation.
AB  - OBJECTIVE: Intravenous immunoglobulin (IVIG) products are known to have
      beneficial immunomodulatory effects on several inflammatory and autoimmune
      disorders. These effects could be attributed to a different inhibitory action on
      complement factors, but other mechanisms could be implicated, e.g.,
      immunocomplexes development and/or anti-idiotypic antibodies. Positive results on
      the reduction of anti-Human Leukocyte Antigens (HLA) antibodies in highly
      sensitized patients have also been found. The present study focuses on the effect
      of IVIG on the reduction of Panel Reactive Antibody level and crossmatch
      positivity in sensitized patients awaiting kidney transplantation. METHODS: The
      study was performed adapting an in vitro assay on sensitized patients' sera in
      waiting list for kidney transplantation. Sera of twelve highly sensitized
      patients were evaluated for the cytotoxicity inhibition after 10% IVIG treatment.
      RESULTS: A reduction of anti- HLA antibody levels was observed in 75% (9/12) of
      treated patients in vitro, while 25% (3/12) resulted unresponsiveness.
      Particularly, our data showed a significantly higher Panel Reactive Antibody
      reduction for T lymphocytes (p<0.010) than B lymphocytes (p<0.032). CONCLUSIONS:
      In this study, we have used an in vitro assay to investigate susceptibility to
      desensitization with IVIG treatment of sensitized patient sera. These findings
      reveal that the variable effect of IVIG on reducing Panel Reactive Antibody in
      our immunized patients could be attributed to a different inhibitory action on
      complement, likely due to the type and the titre of anti-HLA antibodies.

PMID- 24456258
TI  - Evaluation of short-term outcomes after laparoscopically assisted
      abdominoperineal resection for low rectal cancer.
AB  - BACKGROUND: To investigate the feasibility, safety and short-term efficacy of
      laparoscopic techniques applied in the abdominoperineal resection (APR) for low
      rectal cancer. METHODS: The clinical data of 236 patients with APR from January
      2010 to January 2012 were analysed retrospectively, including 100 patients
      underwent laparoscopically assisted APR (LAAPR group), 136 cases of open APR
      (OAPR group). The demographics, tumor and procedure-related parameters,
      perioperative results and short-term oncological outcomes were evaluated using t
      test or chi(2) -test. RESULTS: The demographic data of the two groups were
      comparable. Perioperative results were better after laparoscopic surgery, with
      less intraoperative blood loss (P = 0.017), earlier return of bowel function (P <
      0.05) and lower complication rates (P = 0.015). No significant differences were
      detected between the two groups in operation time, tumor size, specimen length,
      the distance of tumor from the anal verge, lymph nodes removed and the status of
      circumferential resection margin (P > 0.05). During the follow-up period of 17-38
      months (average, 26 months), the overall survival rates were not significantly
      different between the two groups [82.5% (80/97) versus 82.7% (110/133), P >
      0.05]. The differences in recurrence and metastasis between the two groups were
      not statistically significant. CONCLUSION: Laparoscopically assisted APR for low
      rectal cancer is safe and effective. It has the advantages of less bleeding,
      rapid postoperative recovery and fewer complications, without affecting the
      radical degree of the surgery. Further studies are needed to fully assess
      oncological outcomes in the future.

PMID- 24456259
TI  - Ampullary cancer--a separate clinical entity?
AB  - AIMS: Ampullary cancer is a relatively uncommon tumour, with a better prognosis
      than pancreatic cancer. The purpose of this study was to review the recent
      literature on ampullary adenocarcinoma, focusing on histological types and
      prognostic factors. METHODS AND RESULTS: Using PubMed, we carried out a
      comprehensive search of the literature, which was extended to April 2013 to
      retrieve all additional publications. Ampullary cancer comprises two main
      histological subtypes, the pancreatobiliary type and the intestinal type. These
      subtypes have different pathogenetic and clinical characteristics. Clinical and
      histological parameters as well as immunohistochemical markers have been
      identified as significant prognostic factors in ampullary cancer. Moreover,
      several immunohistochemical markers have been studied, not only as prognostic
      factors but as a means of differentiating ampullary from other peri-ampullary
      tumours, and of identifying the exact histological subtype. CONCLUSIONS: The
      considerable differences in the frequencies of the two subtypes of ampullary
      tumours reported in literature reinforce the necessity to define molecular
      markers to distinguish them. Until then, the significance of the histological
      subtype as a prognostic factor should be evaluated cautiously. Future research on
      the pathogenesis of ampullary cancer will possibly suggest that we should stop
      treating this type of cancer as a separate entity.

PMID- 24456260
TI  - Selective Ag(I) binding, H2S sensing, and white-light emission from an easy-to
      make porous conjugated polymer.
AB  - Separating silver (Ag(+)) from lead (Pb(2+)) is one of the many merits of the
      porous polymer framework reported here. The selective metal binding stems from
      the well-defined chelating unit of N-heterocycles, which consists of a triazine
      (C3N3) ring bonded to three 3,5-dimethylpyrazole moieties. Such a rigid and open
      triad also serves as the distinct building unit in the fully conjugated 3D
      polymer scaffold. Because of its strong fluorescence and porosity (e.g., BET
      surface area: 355 m(2)/g), and because of the various types of metal species that
      can be readily taken up, this versatile framework is especially fit for
      functionalization. For example, with AgNO3 loaded, the framework solid exhibits a
      brown color in response to water solutions of H2S, even at the dilution of 5.0
      MUM (0.17 ppm); whereas cysteine and other biologically relevant thiols do not
      cause notable change in color. In another example, tunable white-light emission
      was produced when an Ir(III) complex was doped (e.g., about 0.02% of the polymer
      weight) onto the framework. Mechanistically, the bound Ir(III) centers become
      highly emissive in the orange-red region, complementing the broad, bluish
      emission from the polymer host to result in the overall white-light quality: the
      color attributes of the emission are therefore easily tunable by the Ir(III)
      dopant concentration. With this exemplary study, we intend to highlight metal
      uptake as an effective approach to modify and enrich the properties of porous
      polymer frameworks and to stimulate interest in further examining metal-polymer
      interactions in the context of sensing, separation, catalyzes, and other
      applications. 

PMID- 24456261
TI  - Extraneous epithelial cells from thromboplastin in cell blocks.

PMID- 24456262
TI  - Towards establishing a multiple sclerosis biobank in Jordan.
AB  - Genome-wide association studies (GWAS) have been a promising approach in
      unraveling genetic associations to multiple sclerosis (MS), a complex,
      multifactorial disease. Biobanks are repositories of patient biospecimens and
      information that can promote GWAS research. However, the success of GWAS and
      biobanking is dependent on the level of participation of MS patients in genetic
      research. In order to initiate MS-based biobanking and GWAS research in Jordan,
      the willingness of MS patients to participate in long-term, genetic research in
      Jordan and their preferred type of a consent form were investigated. MS patients
      (289) were recruited for genetic studies. Personal and clinical information were
      collected from those who enrolled in the study. Approximately 96% of MS patients
      agreed to participate in genetic studies. The female:male ratio among patients
      was 2:1 with most patients being diagnosed with relapsing-remitting MS (88%). The
      mean age of onset was 28.3 years, the mean duration of illness was 6 years, and
      the mean Expanded Disability Status Scale was 2.8. Relatedness of parents was
      significantly associated with having secondary-progressive MS. Approximately 85%
      of the patients preferred open consent with 37% of them preferring to renew their
      consent. All the patients approved to be recontacted and update their information
      via accessing their medical files or physicians. These observations support the
      establishment of a specialized MS biobank in Jordan and pave the way to
      participate in international large-scale genetic initiatives. 

PMID- 24456264
TI  - Immunopharmacology of the main herbal supplements: a review.
AB  - It is debated whether the use of herbal supplements in endurance sports, in order
      to have a better performance, is correct or not, from the perspective of both as
      safety and as effectiveness. In this review we try to find out if the most common
      herbal supplements (Echinacea, Rhodiola, Ginseng) are effective in the
      improvement of performance or in the modulation of the immune system. According
      to the results of our review, the prevalent effect is adaptogenic rather than
      ergogenic, with a better tolerance of the exercise induced stress, related to
      enhancement of the whole immune system and decrease of the oxidative damage. 

PMID- 24456265
TI  - Effects of peroxyl radicals on contractility of rabbit aorta and guinea pig
      atria.
AB  - BACKGROUND: High-fat meals may lead to hypotension, oxidative stress and
      increases of lipopolysaccharide (LPS). Contrasting results have been reported
      after treatment of isolated tissues with hydrogen peroxide and LPS, whereas the
      effects of peroxyl radicals, involved in the propagation reaction of
      lipoperoxidation, have not been investigated previously. AIM: In the present
      study, we aimed to evaluate the effects of peroxyl radicals on the contractile
      responses in isolated rabbit aorta and guinea pig atria. METHODS AND RESULTS: We
      treated isolated guinea pig atria, rabbit aorta strips and rings with 2,2'-Azobis
      (2- amidinopropane) dihydrochloride (AAPH). AAPH did not affect isoprenaline
      induced contraction in guinea pig atria, whilst it dose-dependently reduced the
      contractile responses induced in rabbit aorta strips by cumulative doses of
      adrenaline (ADR) and induced an endothelium-independent relaxation of
      noradrenaline (NA)-contracted aorta rings. The effects of KCl-induced and BaCl2
      induced contractions were small. Furthermore, alkalinization with NH4Cl of NA
      contracted aorta rings significantly reduced the vasodilatatory activity of AAPH.
      CONCLUSION: The present study suggests that peroxyl radicals induce acute
      functional alterations on vascular contraction through intracellular pH
      regulation. This finding could be related to the documented after meal increase
      in oxidative burst and endotoxin and the related hypotension.

PMID- 24456266
TI  - Cerebral oxygenation after birth - a comparison of INVOS((r)) and FORE-SIGHTTM
      near-infrared spectroscopy oximeters.
AB  - AIM: To compare absolute values of regional cerebral tissue oxygenation (cStO2 )
      during haemodynamic transition after birth and repeatability during steady state
      for two commercial near-infrared spectroscopy (NIRS) devices. METHODS: In a
      prospective observational study, the INVOS 5100C and FORE-SIGHT were compared on
      12 term newborns delivered by elective caesarean section. During the 10 min
      following umbilical cord clamping, cStO2 was measured simultaneously with the
      neonatal sensors from each device. Repeated measurements were taken the following
      day. RESULTS: Three and 8 min after clamping, the mean cStO2 value increased from
      53.4% (CI 36.8-69.9%) to 86.0% (CI 80.2-91.7%) for INVOS and from 61.6% (CI 55.4
      67.8%) to 82.2% (CI 77.7-86.7%) for FORE-SIGHT. The Bland-Altman plot revealed
      decreasing difference (INVOS minus FORE-SIGHT) (D) in absolute values (A) with
      increasing cStO2 (D = 0.5A - 38.19 p = <0.001). The mean steady-state value on
      day two was 78.4% (CI 74.6-82.2%) and 86.2% (CI 85.0-87.4%) for INVOS and FORE
      SIGHT, respectively. The within-subject standard deviation during steady-state
      repeated measurements was 4.8% +/- 0.86 for INVOS and 2.8% +/- 0.5 for FORE
      SIGHT. CONCLUSION: The INVOS and FORE-SIGHT cStO2 estimates showed oxygenation
      level-dependent difference during birth transition. The better repeatability of
      FORE-SIGHT could be due to the lower response to change in saturation.

PMID- 24456263
TI  - Deep brain stimulation: are astrocytes a key driver behind the scene?
AB  - Despite its widespread use, the underlying mechanism of deep brain stimulation
      (DBS) remains unknown. Once thought to impart a "functional inactivation", there
      is now increasing evidence showing that DBS actually can both inhibit neurons and
      activate axons, generating a wide range of effects. This implies that the
      mechanisms that underlie DBS work not only locally but also at the network level.
      Therefore, not only may DBS induce membrane or synaptic plastic changes in
      neurons over a wide network, but it may also trigger cellular and molecular
      changes in other cells, especially astrocytes, where, together, the glial
      neuronal interactions may explain effects that are not clearly rationalized by
      simple activation/inhibition theories alone. Recent studies suggest that (1) high
      frequency stimulation (HFS) activates astrocytes and leads to the release of
      gliotransmitters that can regulate surrounding neurons at the synapse; (2)
      activated astrocytes modulate synaptic activity and increase axonal activation;
      (3) activated astrocytes can signal further astrocytes across large networks,
      contributing to observed network effects induced by DBS; (4) activated astrocytes
      can help explain the disparate effects of activation and inhibition induced by
      HFS at different sites; (5) astrocytes contribute to synaptic plasticity through
      long-term potentiation (LTP) and depression (LTD), possibly helping to mediate
      the long-term effects of DBS; and (6) DBS may increase delta-opioid receptor
      activity in astrcoytes to confer neuroprotection. Together, the plastic changes
      in these glial-neuronal interactions network-wide likely underlie the range of
      effects seen, from the variable temporal latencies to observed effect to global
      activation patterns. This article reviews recent research progress in the
      literature on how astrocytes play a key role in DBS efficacy. 

PMID- 24456267
TI  - Choosing sensitivity analyses for randomised trials: principles.
AB  - BACKGROUND: Sensitivity analyses are an important tool for understanding the
      extent to which the results of randomised trials depend upon the assumptions of
      the analysis. There is currently no guidance governing the choice of sensitivity
      analyses. DISCUSSION: We provide a principled approach to choosing sensitivity
      analyses through the consideration of the following questions: 1) Does the
      proposed sensitivity analysis address the same question as the primary analysis?
      2) Is it possible for the proposed sensitivity analysis to return a different
      result to the primary analysis? 3) If the results do differ, is there any
      uncertainty as to which will be believed? Answering all of these questions in the
      affirmative will help researchers to identify relevant sensitivity analyses.
      Treating analyses as sensitivity analyses when one or more of the answers are
      negative can be misleading and confuse the interpretation of studies. The value
      of these questions is illustrated with several examples. SUMMARY: By removing
      unreasonable analyses that might have been performed, these questions will lead
      to relevant sensitivity analyses, which help to assess the robustness of trial
      results.

PMID- 24456268
TI  - Bullying and victimization among African American adolescents: a literature
      review.
AB  - TOPIC: Bullying among African American adolescents. PURPOSE: This article reviews
      the current literature on bullying and victimization among African American
      adolescents. It highlights bullying and violence disparity among African American
      adolescents, associated risk and protective factors, and effects of bullying on
      adolescent health. SOURCES USED: Twenty-three English language peer-reviewed
      articles from CINAHL, Pubmed, and Psyc-INFO databases. CONCLUSION: African
      American adolescents have higher rates of bullying and victimization compared to
      other adolescent populations. This review found strong associations among
      bullying involvement, substance abuse, and family factors. Bullying also had a
      significant impact on adolescent health, particularly psychological symptoms and
      school performance.

PMID- 24456269
TI  - The mechanisms and quantification of the selective permeability in transport
      across biological barriers: the example of kyotorphin.
AB  - This paper addresses the mechanisms behind selective endothelial permeability and
      their regulations. The singular properties of each of the seven blood-tissues
      barriers. Then, it further revisits the physical, quantitative meaning of
      permeability, and the way it should be measured based on sound physical chemistry
      reasoning and methodologies. Despite the relevance of permeability studies one
      often comes across inaccurate determinations, mostly from oversimplified data
      analyses. To worsen matters, the exact meaning of permeability is being lost
      along with this loss of accuracy. The importance of proper permeability
      calculation is illustrated with a family of derivatives of kyotorphin, an
      analgesic dipeptide. 

PMID- 24456270
TI  - Tetraoxanes as antimalarials: harnessing the endoperoxide.
AB  - With the emergence of resistance to artemesinin, the need for new antimalarial
      compounds is pressing. Several research groups have made significant
      contributions to the exploration of the use of 1,2,4,5-tetraoxanes and 1,2,4-
      trioxanes as synthetic analogues of artemesinin. This short review highlights the
      recent developments in this field detailing both biological results and useful
      synthetic methodology. In addition, the current understanding of the mode of
      action of this class of compounds has been described. 

PMID- 24456271
TI  - Metallothioneins and synthetic metal chelators as potential therapeutic agents
      for removal of aberrant metal ions from metal-Abeta species.
AB  - Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta
      (Abeta) peptide in the brains of AD patients. Such a process is linked to the
      binding of metal ions (e.g., Cu, Fe and Zn) with Abeta. As a result, metal
      chelation could be used as a rational therapeutic pathway for the treatment of
      AD. In this review, we address some noteworthy advances on the utilization of
      metal chelators, such as native metallothioneins and synthetic compounds, as
      potential therapeutic agents for AD. In addition, the future design and utility
      of metal chelating drugs as well as the strategy pursued to transport metal
      chelators into the brain are highlighted. We believe that this contribution will
      be valuable for the design of metal-chelating drugs for AD treatment. 

PMID- 24456272
TI  - Evolution of drug resistance: insight on TEM beta-lactamases structure and
      activity and beta-lactam antibiotics.
AB  - Since the discovery of the first penicillin bacterial resistance to beta-lactam
      antibiotics has spread and evolved promoting new resistances to pathogens. The
      most common mechanism of resistance is the production of beta-lactamases that
      have spread thorough nature and evolve to complex phenotypes like CMT type
      enzymes. New antibiotics have been introduced in clinical practice, and therefore
      it becomes necessary a concise summary about their molecular targets, specific
      use and other properties. beta-lactamases are still a major medical concern and
      they have been extensively studied and described in the scientific literature.
      Several authors agree that Glu166 should be the general base and Ser70 should
      perform the nucleophilic attack to the carbon of the carbonyl group of the beta
      lactam ring. Nevertheless there still is controversy on their catalytic
      mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due
      to their tolerance to mutations. These mutations lead to an increasing need of
      novel, stronger and more specific and stable antibiotics. The present review
      summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT
      TEM beta-lactamases properties and up to date diagrams of the TEM variants with
      defined phenotype. The activity and structural characteristics of several
      available TEMs in the NCBI-PDB are presented, as well as the relation of the
      various mutated residues and their specific properties and some previously
      proposed catalytic mechanisms. 

PMID- 24456273
TI  - An overview of phytotherapeutic approaches for the treatment of benign prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is the noncancerous growth of the prostate
      gland resulting due to overproliferation of the stromal and glandular elements of
      the prostate and is associated with lower urinary tract symptoms. Natural
      products, containing inherently vast structural diversity than synthetic
      compounds, have been the major resources of bioactive agents and will continue to
      play as protagonists for discovering new drugs. Phytotherapeutic products have
      been used traditionally in developing countries while the use of them as
      complementary alternative medicine is increasing rapidly in developed countries
      for the management of BPH. Although mono preparations (single plant only) are
      available, many industries manufacture combination products (plant extracts) in
      an attempt to provide enhanced efficacy to improve marketability, and to provide
      their own "unique" product that can be registered, because these products have no
      patent protection. The mechanism of action of the phytotherapeutic agents is not
      clearly understood as many in vitro experimental studies have demonstrated
      diverse spectrum of mechanisms. The main mechanisms of action that has received
      the greatest attention are anti-inflammatory, 5alpha-reductase inhibition, and
      more recently growth factor alteration. The current review covers all such
      studies and critiques the efficacy and value of such phytotherapeutic products
      and preparations available for the management of BPH. 

PMID- 24456274
TI  - A simple route to morphology-controlled polydimethylsiloxane films based on
      particle-embedded elastomeric masters for enhanced superhydrophobicity.
AB  - We present a simple route for controlling the surface morphology of
      polydimethylsiloxane (PDMS) films based on a standard replica molding technique
      incorporating a microparticle-embedded elastomeric master for enhancing surface
      wetting properties. The elastomeric masters are simply prepared by embedding
      microparticles (MPs) firmly into a surface of PDMS substrates using an abrasive
      air-jetting (AAJ) that can be potentially scaled up to large-area fabrication.
      The surface geometries of the PDMS masters can be easily controlled by using MPs
      with different shape and size in the AAJ process, resulting in easy control of
      the surface morphologies and resultant wetting and optical properties of the PDMS
      films after replicating. The PDMS masters are found to be highly durable,
      enabling repeated use to produce superhydrophobic PDMS films with similar
      characteristics. In addition, the fabricated PDMS films retain almost constant
      properties even under repetitive compressing and stretching deformations thanks
      to the mechanical robustness enabled by their all-elastomeric architectures. We
      show that the fabricated PDMS surfaces can be potentially employed as self
      cleaning films in glass-based applications, even with complex surfaces, owing to
      their enhanced wetting properties, fairly good optical transparency, and superior
      mechanical stability. 

PMID- 24456276
TI  - Inhalable microorganisms in Beijing's PM2.5 and PM10 pollutants during a severe
      smog event.
AB  - Particulate matter (PM) air pollution poses a formidable public health threat to
      the city of Beijing. Among the various hazards of PM pollutants, microorganisms
      in PM2.5 and PM10 are thought to be responsible for various allergies and for the
      spread of respiratory diseases. While the physical and chemical properties of PM
      pollutants have been extensively studied, much less is known about the inhalable
      microorganisms. Most existing data on airborne microbial communities using 16S or
      18S rRNA gene sequencing to categorize bacteria or fungi into the family or genus
      levels do not provide information on their allergenic and pathogenic potentials.
      Here we employed metagenomic methods to analyze the microbial composition of
      Beijing's PM pollutants during a severe January smog event. We show that with
      sufficient sequencing depth, airborne microbes including bacteria, archaea,
      fungi, and dsDNA viruses can be identified at the species level. Our results
      suggested that the majority of the inhalable microorganisms were soil-associated
      and nonpathogenic to human. Nevertheless, the sequences of several respiratory
      microbial allergens and pathogens were identified and their relative abundance
      appeared to have increased with increased concentrations of PM pollution. Our
      findings may serve as an important reference for environmental scientists, health
      workers, and city planners. 

PMID- 24456277
TI  - Comparing online and face-to-face dissonance-based eating disorder prevention.
AB  - Disordered eating behavior is common in college women. Thus, it is important to
      develop programs to reduce eating disorder (ED) risk. Studies suggest that
      dissonance-based (DB) prevention programs successfully reduce ED risk factors;
      however, face-to-face DB groups lack anonymity and convenience. One way to
      address these barriers is to adapt DB programs for online use. Few studies have
      examined the feasibility of this delivery mode. This study compared the efficacy
      of an online DB program with a face-to-face DB program and an assessment-only
      condition. Undergraduate women (N = 333) recruited from a participant pool at a
      public university in the mid-Atlantic United States participated (n = 107 face-to
      face DB, n = 112 online DB, n = 114 assessment-only). It was hypothesized that:
      (a) participants in the face-to-face and online DB conditions would report
      greater decreases in thin-ideal internalization, body dissatisfaction, and ED
      symptoms at post-testing relative to participants in the assessment-only control
      group, and (b) online and face-to-face programs would yield comparable results.
      Modified intent-to-treat analyses indicated that participants in both conditions
      manifested less body dissatisfaction at post-test compared with assessment-only
      participants; there were no significant differences in outcomes between the two
      modes of program delivery. These findings indicate that DB ED prevention programs
      can be successfully adapted for online use. Future studies should continue to
      refine online adaptations of such programs and examine their effects with samples
      that include older and younger women, and men. 

PMID- 24456278
TI  - Combined approach improves the outcomes of catheter ablation of idiopathic
      ventricular arrhythmias originating from the vicinity of tricuspid annulus.
AB  - BACKGROUND: Ablation of idiopathic ventricular arrhythmias (VAs) originating from
      the vicinity of tricuspid annulus (TA) is often unsuccessful via inferior
      approach. We report the initial experience with catheter ablation of VAs arising
      from the vicinity of the TA via superior approach. METHODS: We retrospectively
      studied 36 patients with VAs arising from the vicinity of TA who underwent
      ablation via transfemoral vein approach first. If patients had a failed prior
      ablation or VAs recurred during follow-up, they were referred for repeat ablation
      via transsubclavian vein approach. RESULTS: Among 36 patients, 11 (30.6%)
      patients (five failed during the index procedure and six recurred during the
      follow-up) were assigned to perform repeat ablation via the transsubclavian vein
      approach. After the final procedure two patients recurred again, and success rate
      increased from 69.5% (25/36) to 94.4% (34/36). Amplitudes of the atrial
      electrograms of all successful ablation sites via the transsubclavian vein
      approach was <0.036 mV. CONCLUSIONS: The transsubclavian vein approach plus
      transfemoral vein approach improve the outcomes of catheter ablation of
      idiopathic VAs originating from the vicinity of TA. The transsubclavian vein
      approach is a feasible alternative for VAs, which has been refractory to ablation
      via the inferior approach.

PMID- 24456279
TI  - Sense of coherence as a protective factor for psychological distress among gay
      men: a prospective cohort study.
AB  - Gay men face a greater risk of psychological distress than heterosexual men, yet
      research on protective factors among gay men has been limited. This prospective
      cohort study investigated whether a sense of coherence (SOC), as a form of
      coping, helps to protect against psychological distress among middle-aged and
      older gay men. A nationwide online survey was conducted among a baseline sample
      of 1135 Australian gay-identified men aged 40 years and older, with a follow-up
      survey 12 months later. SOC was measured using the 13-item SOC Scale.
      Psychological distress was measured using the K10 Psychological Distress Scale.
      Hierarchical regressions were conducted, with analyses controlling for several
      potential risk factors for distress. Over half of participants had moderate or
      high psychological distress. However, baseline distress was significantly lower
      among those with stronger baseline SOC. In addition, baseline SOC significantly
      predicted distress 12 months later. This predictive effect of SOC was independent
      of baseline distress levels and occurred despite a strong correlation between
      baseline and follow-up distress. With SOC appearing to be a protective factor,
      strategies among middle-aged and older gay men that strengthen SOC may assist in
      the prevention and treatment of anxiety and other psychological distress in this
      vulnerable population. 

PMID- 24456280
TI  - Filling up the heme pocket stabilizes apomyoglobin and speeds up its folding.
AB  - Wild type apomyoglobin folds in at least two steps: the ABGH core rapidly,
      followed much later by the heme-binding CDEF core. We hypothesize that the
      evolved heme-binding function of the CDEF core frustrates its folding: it has a
      smaller contact order and is no more complex topologically than ABGH, and thus,
      it should be able to fold faster. Therefore, filling up the empty heme cavity of
      apomyoglobin with larger, hydrophobic side chains should significantly stabilize
      the protein and increase its folding rate. Molecular dynamics simulations allowed
      us to design four different mutants with bulkier side chains that increase the
      native bias of the CDEF region. In vitro thermal denaturation shows that the
      mutations increase folding stability and bring the protein closer to two-state
      behavior, as judged by the difference of fluorescence- and circular dichroism
      detected protein stability. Millisecond stopped flow measurements of the mutants
      exhibit refolding kinetics that are over 4 times faster than the wild type's. We
      propose that myoglobin-like proteins not evolved to bind heme are equally stable,
      and find an example. Our results illustrate how evolution for function can force
      proteins to adapt frustrated folding mechanisms, despite having simple
      topologies. 

PMID- 24456281
TI  - AP180 couples protein retrieval to clathrin-mediated endocytosis of synaptic
      vesicles.
AB  - How clathrin-mediated endocytosis (CME) retrieves vesicle proteins into newly
      formed synaptic vesicles (SVs) remains a major puzzle. Besides its roles in
      stimulating clathrin-coated vesicle formation and regulating SV size, the
      clathrin assembly protein AP180 has been identified as a key player in retrieving
      SV proteins. The mechanisms by which AP180 recruits SV proteins are not fully
      understood. Here, we show that following acute inactivation of AP180 in
      Drosophila, SV recycling is severely impaired at the larval neuromuscular synapse
      based on analyses of FM 1-43 uptake and synaptic ultrastructure. More
      dramatically, AP180 activity is important to maintain the integrity of SV protein
      complexes at the plasma membrane during endocytosis. These observations suggest
      that AP180 normally clusters SV proteins together during recycling. Consistent
      with this notion, SV protein composition and distribution are altered in AP180
      mutant flies. Finally, AP180 co-immunoprecipitates with SV proteins, including
      the vesicular glutamate transporter and neuronal synaptobrevin. These results
      reveal a new mode by which AP180 couples protein retrieval to CME of SVs. AP180
      is also genetically linked to Alzheimer's disease. Hence, the findings of this
      study may provide new mechanistic insight into the role of AP180 dysfunction in
      Alzheimer's disease. 

PMID- 24456283
TI  - A brief report on the efficacy of donepezil in pain management in Alzheimer's
      disease.
AB  - Alzheimer's disease is an advanced dementia. In this disease, little by little
      the brain loses most of its functions. Pain is a prevalent complaint. It seems
      easing the pain had the better recovery to antipsychotic drug in controlling
      agitation in dementia patients. Donepezil is a drug that is used to treat
      Alzheimer's disease. This brief report describes an 83-year-old woman with
      Alzheimer's disease who experienced boredom and changes in attitude for about 1
      year and complained about general pain in her extremity. Starting donepezil
      controlled the patient's symptoms. As soon as the treatment started, all pain was
      dramatically eliminated and her behavior improved. Donepezil may be effective in
      controlling the pain and improve the outcome of these patients.

PMID- 24456284
TI  - Vitamin D supplementation and risk of toxicity in pediatrics: a review of current
      literature.
AB  - CONTEXT: Although vitamin D toxicity is rare in children, increased use of
      vitamin D formulations, re-examination of optimal vitamin D levels, and use of
      higher doses lend potential for an increased incidence of vitamin D toxicity.
      EVIDENCE ACQUISITION: A PubMed search was conducted through May 2013 for cases of
      vitamin D intoxication and vitamin D trials in pediatrics. Safety data were
      collected and reviewed. EVIDENCE SYNTHESIS: A small number of pediatric studies
      tested vitamin D doses at or above the currently recommended upper tolerable
      intake. In children and adolescents, vitamin D excess was rare and usually
      asymptomatic. Recent cases of intoxication relate to errors in manufacturing,
      formulation, or prescription; involve high total intake in the range of 240,000
      to 4,500,000 IU; and present with severe hypercalcemia, hypercalciuria, or
      nephrocalcinosis. However, mild hypercalcemia and hypervitaminosis using
      currently recommended doses have been reported in infants with rickets.
      CONCLUSIONS: Although rare, cases of vitamin D intoxication that present with
      dramatic life-threatening symptoms still occur in children. Moreover, recent
      studies in infants raise a potential need for monitoring vitamin D levels when
      doses at or above the currently recommended upper range are used. Further studies
      are needed to clarify these findings. The Drugs and Therapeutics Committee of the
      Pediatric Endocrine Society suggests obtaining serum 25-hydroxyvitamin D levels
      in infants and children who receive long-term vitamin D supplementation at or
      above the upper level intake that is currently recommended.

PMID- 24456282
TI  - Neuropsychological functioning in childhood-onset psychosis and attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and childhood-onset
      psychosis (COP) are chronic, heterogeneous disorders with symptoms that
      frequently co-occur, but the etiology of their comorbidity is unknown. Studies of
      each disorder indicate that both ADHD and COP are associated with a range of
      neuropsychological weaknesses, but few neuropsychological studies have directly
      compared groups with ADHD and COP. METHODS: Groups with ADHD only (32 F, 48 M),
      COP only (5 F, 5 M), ADHD + COP (9 F, 21 M), and a control group with neither
      disorder (25 F, 44 M) completed a neuropsychological battery that included
      measures of verbal working memory, response inhibition, response speed and
      variability, and selective attention. RESULTS: All three clinical groups
      exhibited significantly lower performance versus the control group on all
      neuropsychological measures, whereas the only significant difference between the
      clinical groups was a significantly larger weakness in verbal working memory in
      the groups with COP. CONCLUSIONS: The frequent co-occurrence between COP and ADHD
      may reflect shared neuropsychological weaknesses that are most pronounced on
      measures of working memory and response variability.

PMID- 24456285
TI  - An innovative LC-MS/MS-based method for determining CYP 17 and CYP 19 activity in
      the adipose tissue of pre- and postmenopausal and ovariectomized women using 13C
      labeled steroid substrates.
AB  - CONTEXT: Does adipose tissue produce steroid hormones like an endocrine organ?
      OBJECT: To clarify whether adipose tissue produces sex steroid hormone like an
      endocrine organ, we estimated several key steroid hormone levels, as well as
      CYP17 and CYP19 activity, in ovariectomized, pre- and postmenopausal women by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). SUBJECTS AND METHODS:
      The subjects were 19 premenopausal (n = 12), postmenopausal (n = 4), and
      ovariectomized women (n = 3) aged 27-68 years. Serum, visceral adipose and sc
      adipose samples were taken from these subjects and stored at -70 degrees C. The
      levels of cortisol, cortisone, progesterone (Prog), androstenedione,
      dehydroepiandrosterone, estrone, estradiol (E2), and T in serum and adipose
      tissue were estimated simultaneously by LC-MS/MS. CYP17 and CYP19 activity in
      tissues were assayed with the use of (13)C-labeled steroid precursors and LC
      MS/MS-based estimation of the metabolites. RESULTS: E2 and Prog levels in the
      sera of postmenopausal or ovariectomized women were less than 10% of those in
      premenopausal women. No marked variations were seen in other hormones. Estrone,
      androstenedione, dehydroepiandrosterone, and Prog levels in the visceral and sc
      tissues of postmenopausal and ovariectomized women were 9-60 times higher than
      those in serum, whereas E2 and T levels were 3- to 7-fold higher than those in
      serum, and cortisol and cortisone levels were 20% of those found for serum. CYP17
      in adipose tissue was found to have 17-hydroxylase and 20,17-lyase activity, with
      each catalytic activity being essentially equal. Therefore, CYP17 in adipose
      tissue is of the testicular/ovarian type but not adrenal type, which has 17
      hydroxylase activity dominant. The presence of CYP19 activity in adipose tissue
      was approximately 3% of CYP17. CONCLUSION: Our findings suggest that adipose
      tissue acts as an endocrine organ, with CYP17 and CYP19 activity playing an
      essential role in sex steroid hormone biosynthesis.

PMID- 24456287
TI  - Skin autofluorescence predicts cardiovascular mortality in patients on chronic
      hemodialysis.
AB  - Tissue accumulation of advanced glycation end products (AGE) is thought to
      contribute to the progression of cardiovascular disease (CVD). Skin
      autofluorescence, a non-invasive measure of AGE accumulation using
      autofluorescence of the skin under ultraviolet light, has been reported to be an
      independent predictor of mortality associated with CVD in Caucasian patients on
      chronic hemodialysis. The aim of this study was to assess the predictive value of
      skin autofluorescence on all-cause and cardiovascular mortality in non-Caucasian
      (Japanese) patients on chronic hemodialysis. Baseline skin autofluorescence was
      measured with an autofluorescence reader in 128 non-Caucasian (Japanese) patients
      on chronic hemodialysis. All-cause and cardiovascular mortality was monitored
      prospectively during a period of 6 years. During the follow-up period, 42 of the
      128 patients died; 19 of those patients died of CVD. Skin autofluorescence did
      not have a significant effect on all-cause mortality. However, age, carotid
      artery intima-media thickness (IMT), serum albumin, high-sensitivity C-reactive
      protein (hsCRP), skin autofluorescence and pre-existing CVD were significantly
      correlated with cardiovascular mortality. Multivariate Cox regression analysis
      showed skin autofluorescence (adjusted hazard ratio [HR] 3.97; 95% confidence
      interval [CI]1.67-9.43), serum albumin (adjusted HR 0.05; 95% CI 0.01-0.32), and
      hsCRP (adjusted HR 1.55; 95% CI 1.18-2.05) to be independent predictors of
      cardiovascular mortality. The present study suggests that skin autofluorescence
      is an independent predictor of cardiovascular mortality in non-Caucasian
      (Japanese) patients on chronic hemodialysis. 

PMID- 24456286
TI  - Teriparatide increases bone formation and bone mineral density in adult women
      with anorexia nervosa.
AB  - CONTEXT: Anorexia nervosa (AN), a prevalent psychiatric disorder predominantly
      affecting women, is characterized by self-induced starvation and low body weight.
      Increased clinical fractures are common, and most women have low bone mineral
      density (BMD). Previously investigated treatments have led to no or modest
      increases in BMD in AN. OBJECTIVE: Our objective was to investigate the effect of
      teriparatide (TPT; human PTH[1-34]), an anabolic agent, on low bone mass in women
      with AN. DESIGN, SETTING, AND PATIENTS: This randomized, placebo-controlled trial
      at a clinical research center included 21 women with AN: 10 (mean age +/- SEM, 47
      +/- 2.7 years) treated with TPT and 11 (47.1 +/- 2.3 years) treated with placebo.
      INTERVENTIONS: TPT (20 MUg s.c.) or placebo was administered for 6 months. MAIN
      OUTCOME MEASURES: Our primary outcome measure was change in BMD of the spine and
      hip by dual-energy x-ray absorptiometry. Secondary outcome measures included
      changes in serum N-terminal propeptide of type 1 procollagen (P1NP), C-terminal
      collagen cross-links, sclerostin, and IGF-1 levels. RESULTS: At 6 months, spine
      BMD increased significantly more with TPT (posteroanterior spine, 6.0% +/- 1.4%;
      lateral spine, 10.5% +/- 2.5%) compared with placebo (posteroanterior spine, 0.2%
      +/- 0.7%, P < .01; lateral spine, -0.6% +/- 1.0%; P < .01). The results remained
      significant after controlling for baseline body mass index, P1NP, and IGF-1.
      Changes in femoral neck (P = .4) and total hip (P = 0.8) BMD were comparable in
      both groups, as were changes in weight. Serum P1NP levels increased after 3
      months of TPT treatment and remained at this higher level at 6 months, whereas
      P1NP levels were unchanged in the placebo group (P = .02). TPT was well-tolerated
      by all subjects. CONCLUSIONS: This study demonstrates that TPT administration
      increases spine BMD substantially after only 6 months of therapy in women with
      AN.

PMID- 24456288
TI  - De-novo designed library of benzoylureas as inhibitors of BCL-XL: synthesis,
      structural and biochemical characterization.
AB  - The prosurvival BCL-2 proteins are attractive yet challenging targets for
      medicinal chemists. Their involvement in the initiation and progression of many,
      if not all, tumors makes them prime targets for developing new anticancer
      therapies. We present our approach based on de novo structure-based drug design.
      Using known structural information from complexes engaging opposing members of
      the BCL-2 family of proteins, we designed peptidomimetic compounds using a
      benzoylurea scaffold to reproduce key interactions between these proteins. A
      library stemming from the initial de novo designed scaffold led to the discovery
      of ligands with low micromolar potency (KD = 4 MUM) and selectivity for BCL-XL.
      These compounds bind in the canonical BH3 binding groove in a binding mode
      distinct from previously known BCL-2 inhibitors. The results of our study provide
      insight into the design of a new class of antagonists targeting a challenging
      class of protein-protein interactions. 

PMID- 24456289
TI  - Studies toward the synthesis of palhinine lycopodium alkaloids: a Morita-Baylis
      Hillman/intramolecular Diels-Alder approach.
AB  - A synthetic route to the isotwistane core of palhinine lycopodium alkaloids is
      described. A Morita-Baylis-Hillman/intramolecular Diels-Alder (IMDA) strategy
      sets the vicinal all-carbon quaternary centers present in this family of natural
      products. The regioselectivity of the IMDA reaction is dictated by the conditions
      employed for silyl enol ether formation, with one set of conditions providing the
      core of cardionine and alternate conditions generating the desired isotwistane
      core of isopalhinine. 

PMID- 24456290
TI  - Basal cell carcinoma overlying a cardiac pacemaker successfully treated using
      Mohs micrographic surgery.

PMID- 24456291
TI  - 3D QSAR based design of novel oxindole derivative as 5HT7 inhibitors.
AB  - To understand the structural requirements of 5-hydroxytryptamine (5HT7) receptor
      inhibitors and to design new ligands against 5HT7 receptor with enhanced
      inhibitory potency, a three-dimensional quantitative structure-activity
      relationship study with comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA) for a data set of 56
      molecules consisting of oxindole, tetrahydronaphthalene, aryl ketone substituted
      arylpiperazinealkylamide derivatives was performed. Derived model showed good
      statistical reliability in terms of predicting 5HT7 inhibitory activity of the
      molecules, based on molecular property fields like steric, electrostatic,
      hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. This is
      evident from statistical parameters like conventional r2 and a cross validated
      (q2) values of 0.985, 0.743 for CoMFA and 0.970, 0.608 for CoMSIA, respectively.
      Predictive ability of the models to determine 5HT7 antagonistic activity is
      validated using a test set of 16 molecules that were not included in the training
      set. Predictive r2 obtained for the test set was 0.560 and 0.619 for CoMFA and
      CoMSIA, respectively. Steric, electrostatic fields majorly contributed toward
      activity which forms the basis for design of new molecules. Absorption,
      distribution, metabolism and elimination (ADME) calculation using QikProp 2.5
      (Schrodinger 2010, Portland, OR) reveals that the molecules confer to Lipinski's
      rule of five in majority of the cases.

PMID- 24456292
TI  - Novel chemotherapeutic strategies in the management of primary amoebic
      meningoencephalitis due to Naegleria fowleri.

PMID- 24456293
TI  - The RHD*weak D type 4.0 allele is predominantly but not exclusively cis
      associated with the altered RHCE*ce(c.48C, c.105T, c.733G, c.744C, c.1025T)
      allele in the French population.

PMID- 24456294
TI  - Synthesis and anticancer activity of some 1,2,3-trisubstituted
      pyrazinobenzimidazole derivatives.
AB  - The synthesis of some new pyrazino[1,2-a]benzimidazole derivatives and
      investigation of their anticancer activities were aimed in this work. Thus, 2
      acetylbenzimidazole was reacted with appropriate alpha-bromoacetophenones and
      potassium carbonate in acetone to give 2-(2-acetyl-1H-benzimidazol-1-yl)-1
      phenylethanone derivatives (3a-d). These diketone compounds were reacted with
      varied benzylamines in acetic acid to obtain 2-benzyl-1-methylidene-3-aryl-1,2
      dihydropyrazino[1,2-a]benzimidazole derivatives (4a-t). The structures of the
      obtained compounds were elucidated by using IR, (1)H-NMR, (13)C-NMR, MS spectral
      data and elemental analyses results. Anticancer activities of the selected
      compounds were investigated in National Cancer Institute, Bethesda, MD. 3c and 4n
      showed remarkable anticancer activity comparing with standard drugs, melphalan
      and cisplatin.

PMID- 24456295
TI  - Biochemical characterization of the delta-carbonic anhydrase from the marine
      diatom Thalassiosira weissflogii, TweCA.
AB  - Diatom genome sequences clearly reveal the presence of different systems for
      HCO3(-) uptake. Carbon-concentrating mechanisms (CCM) based on HCO3(-) transport
      and a plastid-localized carbonic anhydrase (CA, EC 4.2.1.1) appear to be more
      probable than the others because CAs have been identified in the genome of many
      diatoms. CAs are key enzymes involved in the acquisition of inorganic carbon for
      photosynthesis in phytoplankton, as they catalyze efficiently the interconversion
      between carbon dioxide and bicarbonate. Five genetically distinct classes of CAs
      exist, alpha-, beta-, gamma-, delta- and zeta and all of them are metalloenzymes.
      Recently we investigated for the first time the catalytic activity and inhibition
      of the delta-class CA from the marine diatom Thalassiosira weissflogii, named
      TweCA. This enzyme is an efficient catalyst for the CO2 hydration and its
      inhibition profile with sulfonamide/sulfamate and anions have also been
      investigated. Here, we report the detailed biochemical characterization and
      chemico-physical properties of the delta-CA of T. weissflogii. The delta-CA
      encoding gene was cloned and expressed in Artic Express cells and the recombinant
      protein purified to homogeneity. Interesting to note that TweCA has no intrinsic
      esterase activity with 4-nitrophenyl acetate (pNpA) as substrate although the
      phylogenetic analysis showed that delta-CAs are closer to the alpha-CAs than to
      the other classes of such enzymes.

PMID- 24456296
TI  - Charge dissociation at interfaces between discotic liquid crystals: the
      surprising role of column mismatch.
AB  - The semiconducting and self-assembling properties of columnar discotic liquid
      crystals have stimulated intense research toward their application in organic
      solar cells, although with a rather disappointing outcome to date in terms of
      efficiencies. These failures call for a rational strategy to choose those
      molecular design features (e.g., lattice parameter, length and nature of
      peripheral chains) that could optimize solar cell performance. With this purpose,
      in this work we address for the first time the construction of a realistic planar
      heterojunction between a columnar donor and acceptor as well as a quantitative
      measurement of charge separation and recombination rates using state of the art
      computational techniques. In particular, choosing as a case study the interface
      between a perylene donor and a benzoperylene diimide acceptor, we attempt to
      answer the largely overlooked question of whether having well-matching donor and
      acceptor columns at the interface is really beneficial for optimal charge
      separation. Surprisingly, it turns out that achieving a system with contiguous
      columns is detrimental to the solar cell efficiency and that engineering the
      mismatch is the key to optimal performance. 

PMID- 24456297
TI  - How do lesbian couples compare with heterosexual in vitro fertilization and
      spontaneously pregnant couples when it comes to parenting stress?
AB  - AIM: To study parenting stress in lesbian parents and to compare that stress with
      heterosexual parents following in vitro fertilisation (IVF) or spontaneous
      pregnancies. METHODS: This survey took place during 2005-2008 and was part of the
      Swedish multicentre study on gamete donation. It comprised 131 lesbian parents,
      83 heterosexual IVF parents, who used their own gametes, and 118 spontaneous
      pregnancy parents. The participants responded to the questionnaire when the child
      was between 12 and 36-months-old and parenting stress was measured by the Swedish
      Parenting Stress Questionnaire (SPSQ). RESULTS: Lesbian parents experienced less
      parenting stress than heterosexual IVF parents when it came to the General
      Parenting Stress measure (p = 0.001) and the subareas of Incompetence (p <
      0.001), Social Isolation (p = 0.033) and Role Restriction (p = 0.004). They also
      experienced less parenting stress than heterosexual spontaneous pregnancy
      couples, according to the Social Isolation subarea (p = 0.003). Birth mothers
      experienced higher stress than co-mothers and fathers, according to the Role
      Restriction measure (p = 0.041). CONCLUSION: These are reassuring findings,
      considering the known challenges that lesbian families face in establishing their
      parental roles and, in particular, the challenges related to the lack of
      recognition of the co-mother.

PMID- 24456298
TI  - Barriers for students pursuing a surgical career and where the Surgical Interest
      Association can intervene.
AB  - BACKGROUND: There are some concerns that medical student interest in surgery is
      suffering. The aims of this project were to investigate the proportion of medical
      students interested in surgery from years 1 to 4, explore influential attitudinal
      and demographic factors, and establish baseline data to study the future effects
      of the Surgical Interest Association. METHODS: Students were surveyed through an
      audience response system in year orientation sessions. For a majority of the
      analyses, respondents were dichotomized based on expressing an interest in
      surgery or not. RESULTS: There were no significant differences in the interest
      students had for a surgical career between medical student year levels in a cross
      sectional analysis. However, available longitudinal data demonstrated a
      significant decrease in surgical interest from first years in 2012 to second
      years in 2013. Lifestyle, working hours and training length concerns had minimal
      effects as career influences on students interested in surgery, whereas academic
      interest and career opportunities were motivating factors in choosing this
      career. CONCLUSION: The results suggested no difference between levels of
      interest from first to final year students in surgery as a career, though only
      22% of final year students were interested in surgery. This study also suggested
      that promoting the academic and scientific side of surgery, along with career
      opportunities available, may be an important avenue to encourage students into
      surgery. Future research will investigate the changing interests of students in
      surgery longitudinally throughout the medical school and to analyse the effects
      of the Surgical Interest Association.

PMID- 24456299
TI  - To be or not to be empathic: the combined role of empathic concern and
      perspective taking in understanding burnout in general practice.
AB  - BACKGROUND: General practice is stressful and burnout is common among family
      physicians. A growing body of evidence suggests that the way physicians relate to
      their patients could be linked to burnout. The goal of this study was to examine
      how patterns of empathy explained physicians' burnout. METHODS: We surveyed 294
      French general practitioners (response rate 39%), measured burnout, empathic
      concern (EC) and perspective taking (PT) using self-reported questionnaires, and
      modeled burnout levels and frequencies with EC, PT and their interaction in
      linear and logistic regression analyses. RESULTS: Multivariate linear models for
      burnout prediction were associated with lower PT (beta = -0.21, p < 0.001) and
      lower EC (beta = -0.17, p < 0.05). Interestingly, the interaction (EC x PT) also
      predicted burnout levels (beta = 0.11, p < 0.05). The investigation of
      interactions revealed that high scores on PT predicted lower levels of burnout
      independent from EC (odd ratios (OR) 0.37; 95% confidence interval (95% CI) 0.21
      0.65 p < 0.001), and high scores on both EC and PT were protective against
      burnout: OR 0.31; 95% CI 0.15-0.63, p < 0.001). CONCLUSIONS: Deficits in PT alone
      might be a risk factor for burnout, whereas higher PT and EC might be protective.
      Educators should take into account how the various components of empathy are
      potentially associated with emotional outcomes in physicians.

PMID- 24456300
TI  - Polymerase chain reaction detection of avipox and avian papillomavirus in
      naturally infected wild birds: comparisons of blood, swab and tissue samples.
AB  - Avian poxvirus (avipox) is widely reported from avian species, causing cutaneous
      or mucosal lesions. Mortality rates of up to 100% are recorded in some hosts.
      Three major avipox clades are recognized. Several diagnostic techniques have been
      reported, with molecular techniques used only recently. Avipox has been reported
      from 278 different avian species, but only 111 of these involved sequence and/or
      strain identification. Collecting samples from wild birds is challenging as only
      few wild bird individuals or species may be symptomatic. Also, sampling regimes
      are tightly regulated and the most efficient sampling method, whole bird
      collection, is ethically challenging. In this study, three alternative sampling
      techniques (blood, cutaneous swabs and tissue biopsies) from symptomatic wild
      birds were examined. Polymerase chain reaction was used to detect avipoxvirus and
      avian papillomavirus (which also induces cutaneous lesions in birds). Four out of
      14 tissue samples were positive but all 29 blood samples and 22 swab samples were
      negative for papillomavirus. All 29 blood samples were negative but 6/22 swabs
      and 9/14 tissue samples were avipox-positive. The difference between the numbers
      of positives generated from tissue samples and from swabs was not significant.
      The difference in the avipox-positive specimens in paired swab (4/6) and tissue
      samples (6/6) was also not significant. These results therefore do not show the
      superiority of swab or tissue samples over each other. However, both swab (6/22)
      and tissue (8/9) samples yielded significantly more avipox-positive cases than
      blood samples, which are therefore not recommended for sampling these viruses. 

PMID- 24456301
TI  - Singlet oxygen effects on lipid membranes: implications for the mechanism of
      action of broad-spectrum viral fusion inhibitors.
AB  - It was reported recently that a new aryl methyldiene rhodanine derivative, LJ001,
      and oxazolidine-2,4-dithione, JL103, act on the viral membrane, inhibiting its
      fusion with a target cell membrane. The aim of the present study was to
      investigate the interactions of these two active compounds and an inactive
      analogue used as a negative control, LJ025, with biological membrane models, in
      order to clarify the mechanism of action at the molecular level of these new
      broad-spectrum enveloped virus entry inhibitors. Fluorescence spectroscopy was
      used to quantify the partition and determine the location of the molecules on
      membranes. The ability of the compounds to produce reactive oxygen molecules in
      the membrane was tested using 9,10-dimethylanthracene, which reacts selectively
      with singlet oxygen (1O2). Changes in the lipid packing and fluidity of membranes
      were assessed by fluorescence anisotropy and generalized polarization
      measurements. Finally, the ability to inhibit membrane fusion was evaluated using
      FRET. Our results indicate that 1O2 production by LJ001 and JL103 is able to
      induce several changes on membrane properties, specially related to a decrease in
      its fluidity, concomitant with an increase in the order of the polar headgroup
      region, resulting in an inhibition of the membrane fusion necessary for cell
      infection. 

PMID- 24456302
TI  - Confined nanospace synthesis of less aggregated and porous nitrogen-doped
      graphene as metal-free electrocatalysts for oxygen reduction reaction in alkaline
      solution.
AB  - A facile and low-emission strategy is used for preparation of porous nitrogen
      doped graphene (NGR) in a confined nanospace. The negative charged graphene oxide
      (GO) serves as a substrate for deposition of electropositive metal amine complex
      and then thin layer of silica (SiO2) is formed onto the copper amine ion-coated
      GO. Carbonization of copper amine ion-coated GO in a confined nanospace of SiO2
      and the subsequent removal of the Cu particles and SiO2 layer produces less
      aggregated and porous nitrogen-doped graphene (NGR). NGR materials are highly
      active, cheap, and selective metal-free electrocatalysts for the oxygen reduction
      reaction (ORR) in alkaline solution. The electron transfer for ORR at NGR
      catalysts is found to be around 4 at potentials ranging from -0.35 to -0.70 V.
      NGR may be further exploited as potentially efficient and inexpensive nonmetal
      ORR catalysts with good selectivity and long-term stability in alkaline solution.

PMID- 24456303
TI  - Gender differences in high school coaches' knowledge, attitudes, and
      communication about the female athlete triad.
AB  - The objective of this study was to assess high school coaches' knowledge,
      attitudes, communication, and management decisions with respect to the Female
      Athlete Triad and to determine whether results are patterned by coach gender.
      Data were obtained through an online survey of high school coaches (n = 227).
      Significant differences were found between male and female coaches in certain
      attitudes and communication behaviors related to eating and menstrual
      irregularity. School or district level policies may help reduce these differences
      and may help mitigate the health consequences for athletes related to possible
      differential prevention and detection of the comorbidities of the Female Athlete
      Triad. 

PMID- 24456305
TI  - Seasonal patterns of leaf photosynthetic and secondary xylem vascular traits in
      current-year stems of three Sorbus species with contrasting growth habits.
AB  - Seasonal effects of environmental variables on photosynthetic activity and
      secondary xylem formation provide data to demonstrate how environmental factors
      together with leaf ageing during the season control tree growth. In this study,
      we assessed physiological responses in photosynthetic behaviour to seasonal
      climate changes, and also identified seasonal differences in vascular traits
      within differentiating secondary xylem tissue from three diploid species of the
      taxonomically complex genus Sorbus. From sampling day 150, a clear physiological
      segregation of S. chamaemespilus from S. torminalis and S. aria was evident. The
      shrubby species S. chamaemespilus could be distinguished by a higher
      photosynthetic capacity between days 150 and 206. This was reflected in its
      associations with net CO2 assimilation rate (PN), maximum photochemical
      efficiency of PSII (F(v)/F(m)), variable-to-initial fluorescence ratio
      (F(v)/F(0)), potential electron acceptor capacity ('area') in multivariate space,
      and also its associations with log-transformed vessel area and log-transformed
      relative conductivity between days 239 and 268. The maximum segregation and
      differentiation among the examined Sorbus species was on sampling day 206. The
      largest differences between S. torminalis and S. aria were found on day 115, when
      the latter species clearly showed closer associations with high values of vessel
      density and transpiration (E). Sampling day clusters were arranged along an arch
      like gradient that reflected the positioning of the entire growing season in
      multivariate space. This arch-like pattern was most apparent in the case of S.
      chamaemespilus, but was also observed in S. torminalis and S. aria.

PMID- 24456306
TI  - Molecular dynamics simulation studies on the positive cooperativity of the
      Kemptide substrate with protein kinase A induced by the ATP ligand.
AB  - The positive cooperativity of the Kemptide substrate or the ATP molecule with the
      PKA catalytic subunit has been studied by dynamics simulations and free energy
      calculations on a series of binary and ternary models. The results revealed that
      the first ATP binding to the PKA catalytic subunit is energetically favorable for
      the successive Kemptide binding, confirming the positive cooperativity. The key
      residues Thr51, Glu170, and Phe187 in PKA contributing to the positive
      cooperativity have been found. The binding of ATP to PKA induces the positive
      cooperativity through one direct allosteric communication network in PKA from the
      ATP binding sites in the catalytic loop of the large lobe to the Kemptide binding
      sites in the activation segment of the large lobe, two indirect ones from those
      in the glycine-rich loop and the beta3 strand of the small lobe, and from those
      in the catalytic loop to those in the activation segment via the alphaF helix
      media. The Tyr204Ala mutation in the activation segment of PKA causes both the
      decoupling of the cooperativity and the disruption of the corresponding
      allosteric network through the alphaF helix media. 

PMID- 24456308
TI  - Identification of key factors in Accelerated Low Water Corrosion through
      experimental simulation of tidal conditions: influence of stimulated indigenous
      microbiota.
AB  - Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on
      harbor steel structures remain unclear warranting their study under controlled
      experimental tidal conditions. Initial stimulation of marine microbial consortia
      by a pulse of organic matter resulted in localized corrosion and the highest
      corrosion rates (up to 12-times higher than non-stimulated conditions) in the low
      water zone, persisting after nine months exposure to natural seawater.
      Correlations between corrosion severity and the abundance and composition of
      metabolically active sulfate-reducing bacteria (SRB) indicated the importance and
      persistence of specific bacterial populations in accelerated corrosion. One
      phylotype related to the electrogenic SRB Desulfopila corrodens appeared as the
      major causative agent of the accelerated corrosion. The similarity of bacterial
      populations related to sulfur and iron cycles, mineral and tuberculation with
      those identified in ALWC support the relevance of experimental simulation of
      tidal conditions in the management of steel corrosion exposed to harbor
      environments. 

PMID- 24456307
TI  - Racial/ethnic disparities in ADHD diagnosis by kindergarten entry.
AB  - BACKGROUND: Whether and to what extent racial/ethnic disparities in attention
      deficit/hyperactivity disorder (ADHD) diagnosis occur by kindergarten entry is
      currently unknown. We investigated risk factors associated with an ADHD diagnosis
      by kindergarten entry generally, and specifically whether racial/ethnic
      disparities in ADHD diagnosis occur by this very early time period. METHODS:
      Secondary analysis of data from children enrolled in the Early Childhood
      Longitudinal Study-Birth Cohort (ECLS-B), a large, nationally representative
      cohort of U.S. children born in 2001. Data include information from birth
      certificates, parent and teacher questionnaires, and in-person developmental
      assessments conducted with children at intervals from 9 months through
      kindergarten entry. The analytic sample included children enrolled in the ECLS-B
      at the 60-month assessment (N = 6,550). RESULTS: Black children in the United
      States were 70% (1 - OR of .30) less likely to receive an ADHD diagnosis than
      otherwise similar White children. Hispanic children initially appeared to be
      underdiagnosed for ADHD. However, their disparity with Whites became
      statistically nonsignificant after controlling for whether a language other than
      English was primarily spoken in the home. Analyses of kindergarten teacher
      reported classroom behavior indicated that neither Black nor Hispanic children
      displayed less frequent ADHD-related behaviors than Whites. CONCLUSIONS: Although
      they are not less likely to display ADHD-related behaviors, children who are
      Black or being raised in households where non-English is primarily spoken are
      less likely than otherwise similar White children to be diagnosed with ADHD in
      the US.

PMID- 24456311
TI  - Time course analyses of orthographic and phonological priming effects during word
      recognition in a transparent orthography.
AB  - In opaque orthographies, the activation of orthographic and phonological codes
      follows distinct time courses during visual word recognition. However, it is
      unclear how orthography and phonology are accessed in more transparent
      orthographies. Therefore, we conducted time course analyses of masked priming
      effects in the transparent Dutch orthography. The first study used targets with
      small phonological differences between phonological and orthographic primes,
      which are typical in transparent orthographies. Results showed consistent
      orthographic priming effects, yet phonological priming effects were absent. The
      second study explicitly manipulated the strength of the phonological difference
      and revealed that both orthographic and phonological priming effects became
      identifiable when phonological differences were strong enough. This suggests
      that, similar to opaque orthographies, strong phonological differences are a
      prerequisite to separate orthographic and phonological priming effects in
      transparent orthographies. Orthographic and phonological priming appeared to
      follow distinct time courses, with orthographic codes being quickly translated
      into phonological codes and phonology dominating the remainder of the lexical
      access phase.

PMID- 24456310
TI  - Development of purine-derived 18F-labeled pro-drug tracers for imaging of MRP1
      activity with PET.
AB  - Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter
      that has been implicated in the pathology of several neurological diseases and is
      associated with development of multidrug resistance. To enable measurement of
      MRP1 function in the living brain, a series of 6-halopurines decorated with
      fluorinated side chains have been synthesized and evaluated as putative pro-drug
      tracers. The tracers were designed to undergo conjugation with glutathione within
      the brain and hence form the corresponding MRP1 substrate tracers in situ. 6
      Bromo-7-(2-[(18)F]fluoroethyl)purine showed good brain uptake and rapid metabolic
      conversion. Dynamic PET imaging demonstrated a marked difference in brain
      clearance rates between wild-type and mrp1 knockout mice, suggesting that the
      tracer can allow noninvasive assessment of MRP1 activity in vivo. 

PMID- 24456312
TI  - Psychological indices as predictors for phantom shocks in implantable
      cardioverter defibrillator recipients.
AB  - BACKGROUND: A phantom shock-the sensation of an implantable cardioverter
      defibrillator (ICD) discharge in the absence of an actual discharge-is a
      phenomenon that can occur in ICD patients. Little is known about the influence of
      psychological factors on the incidence of phantom shocks. We evaluated
      psychological correlates of phantom shocks 2 years post-ICD implant in a cohort
      of Dutch ICD recipients. METHODS: Consecutive patients (N = 300; 87.5% men; mean
      age = 62.3) willing to participate in a prospective study (Twente ICD Cohort
      Study) on psychological factors in ICD recipients received an ICD between
      September 2007 and February 2010. At baseline, patients complete the 36-item
      Short Form Health Survey, Hospital Anxiety and Depression Scale, and the Type D
      Scale. Lifetime presence of anxiety and depression was assessed with the MINI
      structural interview. RESULTS: During a follow-up of 24 months, 16 patients
      (5.4%) experienced a phantom shock. Median time to (first) phantom shock was 13
      weeks (range 0-48 weeks). In univariable analysis, no significant relationships
      were found between clinical or psychological indices and the occurrence of
      phantom shocks, nor was there an association between phantom shocks and type D
      personality, symptoms of anxiety, or a history of anxiety and depression.
      CONCLUSIONS: Neither symptoms of anxiety and depression nor psychiatric history
      were associated with the occurrence of phantom shocks. Further studies using more
      explorative, qualitative research techniques are warranted to examine the
      correlates of phantom shocks.

PMID- 24456313
TI  - Tolerability of saxagliptin in patients with inadequately controlled type 2
      diabetes: results from 6 phase III studies.
AB  - BACKGROUND: Oral antihyperglycemic drugs used to treat type 2 diabetes mellitus
      (T2DM) vary in safety and tolerability. Treatment-related hypoglycemia and weight
      gain can exacerbate underlying disease.  OBJECTIVE: To evaluate the tolerability
      of saxagliptin using data from phase III clinical trials.  METHODS: Six 24-week
      randomized studies in 4,214 patients with T2DM were assessed. Saxagliptin 2.5 mg
      or 5 mg was compared with placebo in 2 trials of monotherapy in treatment-naive
      patients and in 3 trials of add-on therapy to metformin, glyburide, or a
      thiazolidinedione; initial combination therapy with saxagliptin 5 mg plus
      metformin was compared with metformin monotherapy in treatment-naive patients.
      Data from the monotherapy and add-on studies were pooled; data from the initial
      combination study were analyzed separately. No statistical analyses of between
      group comparisons across studies were conducted for these safety analyses because
      of multiplicity of end points and relative lack of statistical power and because
      small differences not reaching statistical significance have the potential to be
      clinically relevant.   RESULTS: In the pooled analysis, incidence rates for
      adverse events (AEs) with saxagliptin 2.5 mg, 5 mg, and placebo were 72.0%
      (635/882), 72.2% (637/882), and 70.6% (564/799), respectively; rates for serious
      AEs (SAEs) were 3.5% (31/882), 3.4% (30/882), and 3.4% (27/799); rates of
      discontinuation due to AEs were 2.2% (19/882), 3.3% (29/882), and 1.8% (14/799).
      AEs reported in >= 2% of patients receiving saxagliptin and occurring >= 1% more
      frequently with saxagliptin than with placebo were sinusitis, gastroenteritis,
      abdominal pain, and vomiting. In the initial combination study, AE incidence
      rates with saxagliptin 5 mg plus metformin and metformin monotherapy were 55.3%
      (177/320) and 58.5% (192/328), respectively; incidence rates for SAEs were 2.5%
      (8/320) and 2.4% (8/328); and rates of discontinuation due to AEs were 2.5%
      (8/320) and 3.4% (11/328).  CONCLUSION: Saxagliptin 2.5 mg or 5 mg was generally
      well tolerated as monotherapy, add-on combination therapy with other oral
      antihyperglycemic drugs, and initial combination with metformin.  

PMID- 24456314
TI  - Economic burden of urgency urinary incontinence in the United States: a
      systematic review.
AB  - BACKGROUND: The International Continence Society (ICS) identifies several urinary
      incontinence (UI) subtypes: urgency urinary incontinence (UUI), stress UI (SUI),
      and mixed UI (MUI). UUI is a common symptom of overactive bladder (OAB) syndrome.
      Based on the current ICS definition of OAB, all patients with UUI have OAB,
      whereas not all patients with OAB have UUI. Because UUI is a chronic condition
      that is expected to increase in prevalence as the population of elderly
      individuals grows, it is important to understand its economic burden on society
      and patients and its cost components.  OBJECTIVE: To summarize the published
      English language medical literature on estimates of the economic burden of UUI in
      the United States from a societal and patient perspective, including direct costs
      (diagnosis, treatment, routine care [including incontinence pads], and UUI
      associated comorbidities/complications); indirect costs (lost wages by patients
      and caregivers and lost work productivity due to absenteeism and presenteeism);
      and intangible costs (pain, suffering, and decreased health-related quality of
      life).  METHODS: A PubMed search of the literature for articles on the economic
      burden of UUI in the United States was conducted using the search terms (urgency
      urinary incontinence OR urge incontinence OR mixed incontinence OR overactive
      bladder) AND (burden OR cost OR economic) AND (United States), with limits for
      English language, publication from 1991 to 2011, humans, and adults (19+ years).
      Only primary articles of non-neurogenic UUI in the United States were retained. 
      RESULTS: Seven studies were identified that included data on the economic burden
      of UUI in the United States from a societal and patient perspective. Although
      estimates of the total economic burden of UUI include direct, indirect, and
      intangible costs, none of the 7 U.S. studies included all of these cost
      components. Furthermore, the costs of UUI often could not be fully extracted from
      the costs of OAB, which include patients with and without UUI, or the costs of
      other types of UI. The most recent cost analysis incorporated OAB with UUI
      prevalence rates and data on use of each cost component to calculate the total
      annual direct costs in 2007 for adults aged >= 25 years. The estimated total
      national cost of OAB with UUI in 2007 was $65.9 billion, with projected costs of
      $76.2 billion in 2015 and $82.6 billion in 2020. This 2007 estimate was markedly
      higher than those reported in older studies. Direct costs are the main driver of
      the overall cost of UUI in the United States. Studies that assessed patient costs
      indicated that the personal costs of routine care items for UUI and MUI represent
      a meaningful contribution to the overall economic burden of these conditions.
      These substantial personal expenditures may explain why patients reported that
      they were willing to pay considerable amounts for a treatment that would reduce
      the frequency of their UUI episodes.  CONCLUSIONS: UUI in the United States is
      associated with a substantial economic burden from both a societal and patient
      perspective. Studies evaluating the impact of interventions that reduce the
      frequency of UUI ?episodes on the overall economic burden of UUI are warranted. 

PMID- 24456315
TI  - Evaluation of increased adherence and cost savings of an employer value-based
      benefits program targeting generic antihyperlipidemic and antidiabetic
      medications.
AB  - BACKGROUND: A major employer implemented a change to its employee health benefits
      program to allow beneficiaries with diabetes or high cholesterol to obtain
      preselected generic antidiabetic or generic antihyperlipidemic medications with a
      zero dollar copayment. To receive this benefit, plan beneficiaries were required
      to participate in a contracted vendor's case management and/or wellness program. 
      OBJECTIVE: To assess changes in medication adherence and the costs for generic
      antidiabetic and generic antihyperlipidemic medications resulting from
      participation in a zero copay (ZCP) program.   METHODS: This was a retrospective
      pre-post comparison group study, evaluating adherence and cost. Participants
      using an antihyperlipidemic and/or antidiabetic medication during the study
      identification period and post-implementation period for the program were
      considered eligible for the study. Eligible beneficiaries who enrolled in the ZCP
      program during the post-implementation period were considered participants, while
      those who did not enroll during this period were considered nonparticipants. ZCP
      program participants and nonparticipants were matched via a 1-to-1 propensity
      scoring method using age, gender, comorbidity count, medication type
      (antihyperlipidemic, antidiabetic, or both), and baseline adherence as matching
      criteria. The proportion of days covered (PDC) metric expressed as a mean
      percentage was used to assess adherence to medication therapy, while payer cost
      was examined using prescription drug utilization expressed as per member per year
      (PMPY) and cost change per 30 days of medication expressed in dollars.   RESULTS:
      Among participants who were users of antidiabetic medications, the mean adherence
      rate was sustained from pre- to post-implementation (81.8% vs. 81.9%); however,
      it decreased in the matched nonparticipant group (81.9% vs. 73.1%). This
      difference in mean adherence over time between the participants and
      nonparticipants was statistically significant (0.1% vs. -8.8%, P  less than 
      0.001). Similar results were found among users of antihyperlipidemics. The mean
      adherence rate was sustained over time for participants (77.7% vs. 78.3%) but
      declined over time for nonparticipants (77.6% vs. 70.8%). The difference in mean
      change over time was statistically significant between participants and
      nonparticipants (0.6% vs. -6,8%, P  less than  0.001). Average prescription costs
      PMPY increased for participants of the ZCP program during the post-implementation
      period; however, the increase was not larger than the cost increase among
      nonparticipants ($581 vs. $584, P = 0.95). Furthermore, among antihyperlipidemics
      the cost increase post-implementation was actually significantly less for
      participants than nonparticipants ($51 vs. $143, P  less than  0.001). 
      CONCLUSIONS: Plan sponsors are increasingly evaluating the use of value-based
      benefit design (VBBD) to change member behavior. This ZCP program used a
      reduction in cost sharing to incentivize members to use more generic drugs and to
      enroll in a care management coaching program. The study also demonstrated that a
      VBBD program can have a positive impact on adherence and cost outcomes among
      those who participate compared with nonparticipants. 

PMID- 24456316
TI  - BE EMPOWERED, a specialty pharmacy education program for hemophilia B patients,
      impacts adult joint bleeds and pediatric use of RICE.
AB  - BACKGROUND: Traditional education about hemophilia B in hemophilia treatment
      centers (HTCs) and episodic contact with HTCs limit the amount of education
      patients and their caregivers receive. Specialty care providers have frequent,
      continuing contact with patients. Each contact with a specialty care provider
      (e.g., coordinating a refill or addressing a patient inquiry) is another
      opportunity to support patient self-management of the disease and to give counsel
      on appropriate medication administration. The role of specialty pharmacy in
      improving patient self-management and supporting medication management and
      adherence is well established and reported with rheumatoid arthritis, multiple
      sclerosis, and renal transplant. With hemophilia, specialty pharmacies can
      support educational reinforcement of HTCs as well as support patient self
      management and education of medication therapy. Utilization of patient education
      materials and programs can facilitate such a role. BE EMPOWERED, a specialty
      pharmacy education program for hemophilia B patients, is a multimodule education
      program coupled with frequent telephonic outreach.   OBJECTIVE: To provide
      education about hemophilia B, based upon discrete curriculum modules, facilitated
      by a specialty pharmacy-based nurse educator.   METHODS: Patients with hemophilia
      B (or, for children, their caregivers) were enrolled in the BE EMPOWERED program,
      and data were prospectively collected regarding bleeding and hemophilia-specific
      quality of life (QoL) outcomes (n = 21 caregivers, n = 17 adults).  RESULTS: BE
      EMPOWERED was associated with a statistically significant impact on the use of
      RICE (rest, ice, compression, and elevation) by caregivers whose utilization
      increased from 81% to 95% (P = 0.05). Adults in the BE EMPOWERED program
      experienced a statistically significant drop in the annualized bleeding rate
      (ABR), decreasing from 4.7 to 2.5 for total bleeds and decreasing from 3.5 to 1.7
      for joint bleeds (P <= 0.02). For children with hemophilia B, bleeds were less
      common overall, as reported by their caregivers, with a mean ABR of 1.1 before
      and 1.2 following the program. Regarding QoL scores, adults had lower scores
      compared with children enrolled in the program.  CONCLUSIONS: Completion of the
      BE EMPOWERED program was associated with a decrease in total bleeds and in joint
      bleeds in adults and with increased RICE utilization in children, as reported by
      caregivers. QoL scores were lower in adults compared with children, and further
      research is warranted to understand this difference. Future studies may focus on
      the effect of specialty pharmacy as an educational vehicle with potential cost
      benefits. 

PMID- 24456317
TI  - Measuring economic impact of applying daily average consumption limits.
AB  - BACKGROUND: Health plans may achieve cost savings by limiting the daily average
      consumption (DACON) of certain medications and encouraging members and
      prescribers to select lower cost dosing options. Various strengths of a given
      medication may be similarly priced per unit; therefore, a single unit of a higher
      strength medication may cost less than multiple lower-strength units that provide
      the same dose. For instance, a single 10 mg tablet may cost less than two 5 mg
      tablets.  OBJECTIVE: To measure the economic impact of implementing DACON limits
      for selected medications.  METHODS: RegenceRx prescription claims data for the
      top 200 brand and select generic medications from the first quarter of 2011 were
      searched for DACON limit opportunities. DACON limits were placed on medications
      that were available in multiple strengths that were similar in cost, and at least
      one strength was double another (e.g., 5 mg and 10 mg).Phase 1 of the program
      occurred in December 2011 and consisted of messaging to dispensing pharmacies
      (either electronic or direct contact). In Phase 2 (effective January 1, 2012),
      the claims system was coded to prevent payment for prescription claims in
      quantities exceeding DACON limits ( greater than 1.9 tablets/day). During this
      phase, dispensing pharmacists received electronic messaging at the point of
      service recommending a transition to the least costly dosing option. If the
      dispensing pharmacist determined transition was not clinically appropriate, the
      pharmacy was able to contact RegenceRx customer service for an override.Impact
      was determined by analyzing prescription claims for the selected medications for
      the 3 months following implementation of DACON limits (January-March 2012).
      Specific measurements analyzed included number of claims not paid because of
      exceeding DACON limits, health plan administrative burden, and cost avoidance. 
      RESULTS: DACON limits were placed on 41 medications for commercial lines of
      business and 35 medications for Medicare Part D lines of business, based on the
      medication selection criteria (DACON limits were not placed on classes of
      clinical concern for Medicare Part D). A total of 5,100 claims across both
      commercial and Medicare Part D lines of business for January to March 2012 were
      impacted by implementation of DACON limits at the point of service. Duloxetine,
      niacin CR, and generic temazepam were responsible for more than 60% of the DACON
      limit claims volume. Implementing DACON limits resulted in a total cost avoidance
      of approximately $730,000 across both commercial and Medicare Part D lines of
      business for January to March 2012. Duloxetine, niacin CR, and aripiprazole were
      responsible for nearly 60% of the total aggregate cost avoidance. After
      adjustment for health plan administrative costs, the total cost avoidance was
      just under $720,000.  CONCLUSION: Implementing DACON limits on selected
      medications provided a cost avoidance of approximately $720,000 over a 3-month
      period with limited interruption to patient access and relatively low
      administrative burden. This reduction could result in annualized savings of
      nearly $3 million. 

PMID- 24456318
TI  - Discrepancies identified with the use of prescription claims and diagnostic
      billing data following a comprehensive medication review.
AB  - BACKGROUND: The University of Florida College of Pharmacy's Medication Therapy
      Management Communication and Care Center (UF MTMCCC) provides medication therapy
      management (MTM) services to patients enrolled in a State of Florida Medicaid
      Waiver Program: Medicaid for the Aged and Disabled. To provide these services, UF
      MTMCCC was given access to patients' prescription claims data and diagnostic
      billing data in the form of ICD-9 codes. Prior to calling a patient, a
      precomprehensive medication review (CMR) work-up was performed to identify
      potential medication-related problems (MRPs) and/or health-related problems
      (HRPs). Based on information provided by the patient in relation to
      comorbidities, medications, and medical history during the interactive telephone
      conversation, problems were either confirmed or eliminated. All of the reported
      information was also assessed to identify any new MRPs or HRPs. Accordingly,
      telephonic MTM services have the potential to bridge the gap between pharmacy
      claims data and patient self-reported information, since the MTM services
      provided rely on the accuracy of both informational resources.  OBJECTIVE: To
      determine the degree of discrepancy in patient-reported information regarding
      chronic comorbidities and medications versus diagnostic billing data (ICD-9 codes
      for chronic comorbidities) and pharmacy claims data (medications) when providing
      MTM services during an interactive telephonic comprehensive medication review. 
      METHODS: A retrospective chart review (n = 147 patients) was performed for
      patients who received a telephonic CMR. Pharmacy claims data and diagnostic
      billing data, in conjunction with the pre-CMR work-up data, were used to identify
      discrepancies in information obtained from the patient during the CMR. During the
      chart review, identified MRPs or HRPs were categorized as "confirmed" (patient
      reported the problem exists and/or it was deduced from the presence/absence of a
      medication that the problem does exist); "eliminated" (patient reported the
      problem does not exist and/or it was deduced from the presence/absence of a
      medication that the problem does not exist); or "new" (a problem that was not
      identified during precall identification of problems, but following the CMR
      interaction, it was determined that a problem now exists). The study evaluated
      the discrepancies before and after a CMR telephonic interaction in the following
      categories: medications, chronic comorbidities, level 1 drug-drug interactions,
      level 2 drug-drug interactions, gaps in therapy, therapeutic duplications, lack
      of therapy, preferred drug list alternatives, combination products, and tobacco
      use. Percent discrepancy was calculated as the sum of new and eliminated data
      elements divided by the total number of data elements for each MRP or HRP. 
      RESULTS: The percent discrepancy observed was 42% for medications, 41% for
      chronic comorbidities, 77% for level 1 drug-drug interactions, 93% for level 2
      drug-drug interactions, 35% for gaps in therapy, 87% for therapeutic
      duplications, 26% for lack of therapy, 36% for preferred drug list alternatives,
      42% for combination products, and 54% discrepancy for report of tobacco use.
      Overall, 4,441 data elements were identified as confirmed, eliminated, or new
      across the 147 CMRs. Among those data elements, 56% of the data was confirmed;
      23% was eliminated; and 21% was discovered as new.  CONCLUSIONS: The study met
      its objective in determining the degree of discrepancies that existed when
      prescription claims data and ICD-9 billing data were used to identify MRPs and/or
      HRPs versus using patient-reported data. Data revealed that the presence of
      discrepancy is relatively large depending on the category, indicating a
      difficulty in accurately making recommendations with incomplete data or solely
      based on prescription claims and billing data. MTM services with patient
      interaction are vital in identifying information that allows for more appropriate
      decision making. 

PMID- 24456319
TI  - Incremental health care resource utilization and economic burden of venous
      thromboembolism recurrence from a U.S. payer perspective.
AB  - BACKGROUND: The third leading cause of cardiovascular-associated death, venous
      thromboembolism (VTE), represents a significant health care and economic burden.
      Although the burden of a one-time VTE event has been assessed, there are limited
      data regarding the burden of VTE recurrence. OBJECTIVE: To assess the rate and
      predictors of VTE recurrence within 1 year in the United States and evaluate the
      incremental health care resource utilization and costs associated with such VTE
      recurrences. METHODS: Patients (>= 18 years) diagnosed with deep vein thrombosis
      and/or pulmonary embolism between January 1, 2008, and December 31, 2010, were
      identified from the Truven Health Analytics MarketScan Commercial and Medicare
      databases. The earliest VTE diagnosis was defined as the index VTE event.
      Patients were required to have 12 months of continuous insurance coverage before
      (baseline period) and after (follow-up period) the index event. Patients were
      further required to have initiated anticoagulant usage within 30 days of the
      index VTE event and have at least 30 days of treatment. The incidence of
      recurrent VTE, defined as a hospitalization or emergency room (ER) visit with a
      VTE diagnosis in the follow-up period, was determined for the commercially
      insured and Medicare populations separately. A proportional hazards model was
      used to assess the predictors of time to VTE recurrences. All cause and VTE
      related health care resource utilization including hospitalizations, length of
      stay, outpatient medical service claims, and outpatient pharmacy claims were
      assessed along with the associated costs incurred during the 30-day and 12-month
      post-index event periods. Commercially insured and Medicare patients with and
      without recurrent VTE were evaluated and compared separately. Generalized linear
      models were used to further assess the incremental cost burden of recurrent VTE.
      RESULTS: Among the commercially insured population, 29,275 patients were
      diagnosed with VTE and received anticoagulant therapy. A recurrence of VTE
      associated with a hospitalization or ER visit occurred within 12 months of the
      index VTE in 15.4% of patients with a mean time to recurrence of 74.1 days. Among
      the Medicare insured population (n = 14,509), 11.4% of patients experienced
      another VTE with a mean time to recurrence of 115.6 days. A consistent predictor
      of VTE recurrence across both populations was greater comorbidity as indicated by
      Charlson Comorbidity Index scores. Among commercially insured VTE patients, total
      payments for health care resource utilization for all causes, including
      inpatient, outpatient medical services, and outpatient pharmacy use were higher
      for patients with a recurrent VTE relative to those without a recurrent VTE
      ($82,110 [$106,918] vs. $36,918 [$54,852], P  less than  0.001). The primary
      driver for the higher health care payments was greater use of inpatient care.
      Total payments for VTE-related resource use was also greater for patients with a
      VTE recurrence ($38,591 [$51,479] vs. $15,123 [$22,186], P  less than  0.001)
      with the majority (62.9%) attributed to care that took place within 30 days of
      the index VTE. After adjustment for key patient characteristics, VTE recurrence
      was associated with 2.2-fold and 3.0-fold higher post-index health care payments
      for all causes and for VTE-related claims, respectively. Similar results were
      observed for the Medicare population. CONCLUSIONS: VTE recurrence associated with
      a hospitalization or ER visit is associated with substantial health care resource
      utilization, which is primarily inpatient care undergone within the first 30 days
      following an initial VTE event. Thus, a sizeable portion of the economic burden
      of recurrent VTE is also incurred during this short period of time following an
      initial VTE event. Given that rates of VTE recurrence were high among patients
      identified as having received anticoagulant treatment, strategies to improve
      anticoagulation therapy among VTE patients in addition to other preventative
      measures are needed to lessen the health care and economic burdens of VTE.

PMID- 24456320
TI  - Analysis of gastrointestinal prophylaxis in patients receiving dual antiplatelet
      therapy with aspirin and clopidogrel.
AB  - BACKGROUND: Dual antiplatelet therapy (DAPT) has been found to reduce the risk of
      cardiac death, myocardial infarction, stroke, and stent thrombosis following
      acute coronary syndrome and percutaneous coronary intervention. However, this
      therapy has also been shown to increase the risk of gastrointestinal (GI)
      bleeding as high as 2-fold, especially in patients with multiple risk factors.
      Proton pump inhibitor (PPI) therapy decreases this risk. The current consensus
      document on reducing GI risks associated with antiplatelet agents no longer
      recommends PPI therapy for all patients receiving aspirin (ASA) and clopidogrel.
      The consensus recommendation reserves PPI therapy for patients receiving DAPT
      with a history of upper GI bleeding or prespecified risk factors for GI bleeding.
      OBJECTIVES: To (a) describe the use of GI prophylaxis in patients on DAPT with
      ASA and clopidogrel and (b) assess the incidence of adverse outcomes that
      occurred during readmissions within 6 months of the index hospitalization.  
      METHODS: A retrospective chart review of patients receiving DAPT between February
      1, 2011, and October 15, 2011, was performed to assess the appropriateness of GI
      prophylaxis based on the current consensus document. Therapy was defined as
      appropriate if an indication for prophylaxis was present and PPI therapy was
      prescribed, or if no indication was present and no GI prophylaxis was given.
      Inappropriate prophylaxis was defined as no indication for GI prophylaxis yet
      therapy received, or prophylaxis indicated but incorrect prophylaxis prescribed.
      Incorrect prophylaxis included no prophylaxis, histamine H2 blocker therapy,
      antacid, or combination therapy. During subsequent hospitalizations in the 6
      month period following discharge from the index admission, patients were assessed
      for the development of vascular-, GI-, and PPI-related adverse events.   RESULTS:
      250 patients receiving DAPT during the study period were evaluated.
      Gastrointestinal prophylaxis was appropriate in 48% (119/250) of patients. Of the
      remaining patients, 56.4% (74/131) met guideline criteria for GI prophylaxis but
      did not receive a PPI at discharge, whereas 43.5% (57/131) of patients received
      GI prophylaxis when not indicated. Thirty-three adverse events were identified
      during readmissions, with the most common type being vascular followed by GI and
      PPI adverse events, respectively.   CONCLUSION: More than half of the patients
      did not receive GI prophylaxis appropriately. The most common reason for
      nonadherence to the consensus document was no prophylaxis when indicated.
      Vascular events could not be directly attributed to PPI use, and GI events
      occurred despite prophylaxis. Overall, there was a low incidence of adverse
      events related to the use of PPI therapy. 

PMID- 24456321
TI  - Adherence to national recommendations for safe methotrexate dispensing in
      community pharmacies.
AB  - BACKGROUND: The number of patients using methotrexate (MTX) has increased during
      the last decade. Because of the narrow therapeutic range and potential risks of
      incorrect use, vigilance is required when dispensing MTX. In 2009, the Royal
      Dutch Pharmacists Society, in accordance with the Dutch Health Care Inspectorate,
      published safe MTX dispensing recommendations for community pharmacies.
      OBJECTIVE: To examine adherence to recommendations aimed at safe ?MTX dispensing.
      METHODS: This study was conducted within a convenience sample of 78 community
      pharmacies belonging to the Utrecht Pharmacy Practice Network for Education and
      Research (UPPER). Data were collected in May 2011. RESULTS: 95 pharmacists and
      337 pharmacy technicians were interviewed to assess self-reported adherence with
      dispensing recommendations. In addition, medication records for patients using
      MTX were extracted in 52 pharmacies in order to objectively assess adoption of
      recommendations. More than 75% of the pharmacists and pharmacy technicians
      reported to be adherent to 6 of the 11 recommendations. There are variations in
      reported adherence between team members working in 1 pharmacy; higher adherence
      rates ( greater than 75%) for the pharmacy team as a whole were only shown for 2
      recommendations (recording of day of intake on the label and moment of
      authorization by the pharmacist). The medication records showed that adherence
      with working procedures significantly increased: The number of dispensed records
      with notification of the day of intake on the medication label increased from
      9.9% of the records per pharmacy in 2008 to 77.1% in 2010 (P  less than  0.001).
      CONCLUSIONS: Dutch community pharmacies seem to be adherent to most safe
      dispensing recommendations. However, inconsistencies exist between team members
      that emphasize the importance of addressing this issue and discussing
      recommendations within the team, as there is still room for improvement to ensure
      safe dispensing.

PMID- 24456322
TI  - PCMHs, ACOs, and medication management: lessons learned from early research
      partnerships.
AB  - The Patient Protection and Affordable Care Act has greatly accelerated the
      formation of team-based models of care delivery, primarily accountable care
      organizations (ACOs) and patient-centered medical homes (PCMHs).  Many have
      written about the need to incorporate medication management services into these
      systems in order to improve care and reduce total health care costs. Two primary
      ways of doing so have emerged: (1) an embedded model, whereby pharmacists are
      employed directly by a physician practice, or (2) a "virtual care team" model,
      whereby a PCMH or ACO develops an arrangement with external pharmacists in
      community settings to provide coordinated services. 

PMID- 24456323
TI  - Pharmacists' role in the care of patients with heart failure: review and future
      evolution.

PMID- 24456324
TI  - Basal cell carcinoma of the ala nasi arising in a port wine stain treated using
      mohs micrographic surgery and local flap reconstruction.

PMID- 24456325
TI  - The role of insulin against hydrogen peroxide-induced oxidative damages in
      differentiated SH-SY5Y cells.
AB  - Exogenous hydrogen peroxide (H2O2) can easily penetrate into biological membranes
      and enhance the formation of other reactive oxygen species (ROS). In the present
      study, we have investigated the neuroprotective effects of insulin on H2O2
      induced toxicity of retinoic acid (RA)-differentiated SH-SY5Y cells. To measure
      the changes in the cell viability of SH-SY5Y cells at different concentrations of
      H2O2 for 24 h, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
      (MTT)-based assay was used and a 100 uM H2O2 was selected to establish a model of
      H2O2-induced oxidative stress. Further assays showed that 24 h of 100 uM H2O2
      induced significant changes in the levels of lactate dehydrogenase (LDH), nitric
      oxide (NO), ROS, and calcium ion (Ca2+) in neuronal cells, but insulin can
      effectively diminish the H2O2-induced oxidative damages to these cells. Moreover,
      cells treated with insulin increased H2O2-induced suppression of glutathione
      levels and exerted an apparent suppressive effect on oxidative products. The
      results of insulin treatment with SH-SY5Y cells increased the Bcl-2 levels and
      decreased the Akt levels. The treatment of insulin had played a protective effect
      on H2O2-induced oxidative stress related to the Akt/Bcl-2 pathways.

PMID- 24456326
TI  - Evidence of presence of Mycobacterium tuberculosis in bovine tissue samples by
      multiplex PCR: possible relevance to reverse zoonosis.
AB  - Bovine tuberculosis, caused by Mycobacterium bovis, remains one of the most
      important zoonotic health concerns worldwide. The transmission of Mycobacterium
      tuberculosis from humans to animals also occurs especially in countries where
      there is close interaction of humans with the animals. In the present study,
      thirty bovine lung tissue autopsy samples from an organized dairy farm located in
      North India were screened for the presence of Mycobacterium tuberculosis complex
      by smear microscopy, histopathological findings and PCR. Differential diagnosis
      of M. tuberculosis and M. bovis was made based on the deletion of mce-3 operon in
      M. bovis. The present study found eight of these samples positive for M.
      tuberculosis by multiplex PCR. Sequencing was performed on two PCR-positive
      representative samples and on annotation, and BLAST analysis confirmed the
      presence of gene fragment specific to Mycobacterium tuberculosis. The presence of
      M. tuberculosis in all the positive samples raises the possibility of human-to
      cattle transmission and possible adaptation of this organism in bovine tissues.
      This study accentuates the importance of screening and differential diagnosis of
      Mycobacterium tuberculosis complex in humans and livestock for adopting effective
      TB control and eradication programmes. 

PMID- 24456327
TI  - Diuretics in the treatment of hypertension. Part 2: loop diuretics and potassium
      sparing agents.
AB  - INTRODUCTION: Diuretics enhance the renal excretion of Na(+) and water due to a
      direct action at different tubular sites of the nephron where solute re
      absorption occurs. AREAS COVERED: This paper focuses on the mechanism of action,
      pharmacodynamics, antihypertensive effects, adverse effects, interactions and
      contraindications of loop diuretics and potassium-sparing agents (including
      mineralocorticoid receptor antagonists (MRAs) and epithelial Na(+) channel
      blockers). EXPERT OPINION: Loop diuretics are less effective than thiazide
      diuretics in lowering blood pressure, so that their major use is in edematous
      patients with congestive heart failure (HF), cirrhosis with ascites and nephritic
      edema. MRAs represent a major advance in the treatment of resistant hypertension,
      primary and secondary hyperaldosteronism and in patients with systolic HF to
      reduce the risks of hospitalization and of premature death. Potassium-sparing
      diuretics when coadministered with diuretics (thiazides and loop diuretics)
      working at more proximal nephron locations reduce the risk of hypokalemia and
      hypomagnesemia and the risk of cardiac arrhythmias. At the end of the article,
      the basis for the combination of diuretics with other antihypertensive drugs to
      achieve blood pressure targets is presented.

PMID- 24456328
TI  - Changes in hepcidin and reticulocyte hemoglobin equivalent levels in response to
      continuous erythropoietin receptor activator administration in hemodialysis
      patients: a randomized study.
AB  - Inadequate iron availability limits the response to erythropoiesis-stimulating
      agents (ESA) and hepcidin is a key regulator of iron metabolism. However, there
      is little information concerning time-dependent changes in hepcidin in response
      to the change of accelerated iron demand due to ESA-induced erythropoiesis. In
      this study, iron-related parameters, including hepcidin levels, were explored in
      comparison to patients receiving continuous erythropoietin receptor activator
      (CERA) and epoetin beta (EPO) treatment. Ninety-four patients were randomized to
      receive monthly CERA (N = 47) or EPO three times/week (N = 47). After the
      titration period, hemoglobin levels and iron-related parameters were examined.
      Data for 71 patients were evaluated (CERA, N = 34; EPO, N = 37). Compared with
      EPO treatment, CERA treatment caused significant decreases within 1 week in
      hepcidin (-93.5 +/- 46.9 vs. -1.3 +/- 38.3 ng/mL, P < 0.01), reticulocyte
      hemoglobin equivalent (Ret-He) (-4.03 +/- 2.64 vs. -1.13 +/- 1.41 pg, P < 0.01),
      ferritin (-58.9 +/- 30.5 vs. -12.2 +/- 23.8 ng/mL, P < 0.01) and transferrin
      saturation (-13.2 +/- 9.1 vs. 1.0 +/- 11.9%, P < 0.01) and significant increases
      within 2 weeks in the levels of hemoglobin (0.42 +/- 0.38 vs. -0.02 +/- 0.48
      g/dL, P < 0.01). In conclusion, hepcidin, Ret-He, ferritin and transferrin
      saturation levels decreased within 1 week and hemoglobin increased within 2 weeks
      after CERA administration. Time course of iron-related parameters including
      hepcidin demonstrated accelerated iron utilization appropriately according to ESA
      induced erythropoiesis.

PMID- 24456329
TI  - DNA content analysis of colorectal cancer defines a distinct 'microsatellite and
      chromosome stable' group but does not predict response to radiotherapy.
AB  - Colorectal cancers (CRC) are thought to have genetic instability in the form of
      either microsatellite instability (MSI) or chromosomal instability (CIN).
      Recently, tumours have been described without either MSI or CIN, that is,
      microsatellite and chromosome stable (MACS) CRCs. We investigated the (i)
      frequency of the MACS-CRCs and (ii) whether this genotype predicted
      responsiveness to neoadjuvant chemoradiotherapy. To examine the frequency of MACS
      CRCs, DNA content (ploidy) was examined in 89 sporadic microsatellite-stable CRCs
      using flow cytometry. The tumours were also screened for mutations in
      KRAS/BRAF/TP53/PIK3CA by QMC-PCR. To examine the value of tumour ploidy in
      predicting response to chemoradiotherapy, DNA content was tested in a separate
      group of 62 rectal cancers treated with neoadjuvant chemoradiotherapy. Fifty-one
      of 89 CRCs (57%) were aneuploid and 38 (43%) were diploid. There was no
      significant association between mutations in TP53/KRAS/BRAF/PIK3CA and ploidy.
      Testing of association between mutations revealed only mutual exclusivity of
      KRAS/BRAF mutation (P < 0.001). Of the 62 rectal cancers treated with neoadjuvant
      chemoradiotherapy, 22 had responded (Mandard tumour regression grade 1/2) and 40
      failed to respond (Grade 3-5). Twenty-five of 62 (40%) tumours were diploid, but
      there was no association between ploidy and response to therapy. We conclude that
      MACS-CRCs form a significant proportion of microsatellite-stable CRCs with a
      mutation profile overlapping that of CRCs with CIN. A diploid genotype does not,
      however, predict the responsiveness to radiotherapy. 

PMID- 24456330
TI  - Pathobiological properties of the ubiquitin ligase Nedd4L in melanoma.
AB  - A recent global gene expression profiling study unexpectedly showed that
      activated oncogenic NRAS may recruit neural precursor cell expressed,
      developmentally downregulated 4L (Nedd4L; a human homologue of Nedd4-2) in
      cultured melanoma cells. However, whether Nedd4L was expressed in melanoma
      tissues or participated in melanoma carcinogenesis remains to be clarified. Here,
      we investigated the expression status of Nedd4L in human melanocytes, benign nevi
      and melanoma tissue specimens and subsequently attempted to determine the role of
      Nedd4L in melanoma cell growth. Immunohistochemical staining revealed that Nedd4L
      was not present in any non-tumorous melanocytes or in 18 benign nevi tissues, but
      it was detected in 34 of 79 cutaneous melanomas and 9 of 32 nodal metastatic
      melanomas. Downregulation of Nedd4L significantly reduced the growth of cultured
      G361 melanoma cells in vitro. Moreover, exogenous Nedd4L expression significantly
      promoted the growth of A2058 melanoma cells in vivo in a xenograft assay. The
      present findings indicate that Nedd4L expression may be increased to facilitate
      tumour growth in many melanomas. 

PMID- 24456331
TI  - Islets of Langerhans from prohormone convertase-2 knockout mice show alpha-cell
      hyperplasia and tumorigenesis with elevated alpha-cell neogenesis.
AB  - Antagonism of the effects of glucagon as an adjunct therapy with other glucose
      lowering drugs in the chronic treatment of diabetes has been suggested to
      aggressively control blood glucose levels. Antagonism of glucagon effects, by
      targeting glucagon secretion or disabling the glucagon receptor, is associated
      with alpha-cell hyperplasia. We evaluated the influence of total glucagon
      withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice
      (PC2-ko), in which alpha-cell hyperplasia is present from a young age and
      persists throughout life, in order to understand whether or not sustained
      glucagon deficit would lead to islet tumorigenesis. PC2-ko and wild-type (WT)
      mice were maintained drug-free, and cohorts of these groups sampled at 3, 12 and
      18 months for plasma biochemical and morphological (histological,
      immunohistochemical, electron microscopical and image analytical) assessments. WT
      mice showed no islet tumours up to termination of the study, but PC2-ko animals
      displayed marked changes in islet morphology from alpha-cell
      hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these
      latter being first encountered at 6-8 months. Islet hyperplasias and tumours
      primarily consisted of alpha-cells associated to varying degrees with other islet
      endocrine cell types. In addition to substantial increases in islet neoplasia,
      increased alpha-cell neogenesis associated primarily with pancreatic duct(ule)s
      was present. We conclude that absolute blockade of the glucagon signal results in
      tumorigenesis and that the PC2-ko mouse represents a valuable model for
      investigation of islet tumours and pancreatic ductal neogenesis. 

PMID- 24456334
TI  - Application of the "hybrid approach" to chronic total occlusion interventions: a
      detailed procedural analysis.
AB  - OBJECTIVE: To assess the outcomes of the "hybrid" approach to chronic total
      occlusion (CTO) percutaneous coronary interventions (PCIs). BACKGROUND: The
      "hybrid approach" to CTO PCI advocates appropriate and early change of crossing
      strategy to maximize success, safety, and efficiency. METHODS: We prospectively
      recorded and analyzed detailed step-by-step procedural data in 73 consecutive CTO
      PCI cases performed by a single operator between July 2011 and August 2012.
      RESULTS: Technical success was achieved in 66 of 73 cases (90.4%). Mean patient
      age was 65 +/- 7 years, and 30% had prior coronary artery bypass surgery. Dual
      injection was used in 78%. The primary approach was retrograde in 9 cases (12.5%)
      and antegrade in 64 cases (87.5%), of whom 25 cases (39.1%) underwent retrograde
      attempt after failed antegrade approach. The initial crossing approach was
      successful in 40 cases (54.8%), but 32 cases (44%) required 3.6 +/- 1.4 approach
      changes (range 2-7). Antegrade wire escalation, antegrade dissection/reentry, and
      retrograde crossing were utilized in 97.2%, 46.6%, and 46.6% of cases,
      respectively. Among successful cases, the final CTO crossing technique was
      antegrade wire escalation in 50.0%, antegrade dissection/reentry in 24.2%, and
      retrograde in 25.8%. The mean procedure time, fluoroscopy time, and air kerma
      radiation exposure until CTO crossing or stopping the procedure were 66 +/- 55
      minutes, 25 +/- 23 minutes, and 2.3 +/- 1.9 Gray, respectively. Three patients
      (4.1%) had a major complication. CONCLUSION: In the "hybrid approach" to CTO PCI,
      changes in crossing strategy were needed in approximately half the cases,
      resulting in high success and low complication rates.

PMID- 24456332
TI  - Therapeutic reversal of chronic alcohol-related steatohepatitis with the ceramide
      inhibitor myriocin.
AB  - Alcohol-related liver disease (ALD) is associated with steatohepatitis and
      insulin resistance. Insulin resistance impairs growth and disrupts lipid
      metabolism in hepatocytes. Dysregulated lipid metabolism promotes ceramide
      accumulation and oxidative stress, leading to lipotoxic states that activate
      endoplasmic reticulum (ER) stress pathways and worsen inflammation and insulin
      resistance. In a rat model of chronic alcohol feeding, we characterized the
      effects of a ceramide inhibitor, myriocin, on the histopathological and
      ultrastructural features of steatohepatitis, and the biochemical and molecular
      indices of hepatic steatosis, insulin resistance and ER stress. Myriocin reduced
      the severity of alcohol-related steatohepatitis including the abundance and sizes
      of lipid droplets and mitochondria, inflammation and architectural disruption of
      the ER. In addition, myriocin-mediated reductions in hepatic lipid and ceramide
      levels were associated with constitutive enhancement of insulin signalling
      through the insulin receptor and IRS-2, reduced hepatic oxidative stress and
      modulation of ER stress signalling mechanisms. In conclusion, ceramide
      accumulation in liver mediates tissue injury, insulin resistance and lipotoxicity
      in ALD. Reducing hepatic ceramide levels can help restore the structural and
      functional integrity of the liver in chronic ALD due to amelioration of insulin
      resistance and ER stress. However, additional measures are needed to protect the
      liver from alcohol-induced necroinflammatory responses vis-a-vis continued
      alcohol abuse. 

PMID- 24456333
TI  - The increased gastroprotective effect of pioglitazone in cholestatic rats: role
      of nitric oxide and tumour necrosis factor alpha.
AB  - The prevalence of gastric ulcers is high in cholestatic patients, but the exact
      mechanism of this increased frequency remains uncertain. It has been shown that
      pioglitazone accelerates the healing of pre-existing gastric ulcers. The present
      study was designed to investigate the effect of pioglitazone, on the gastric
      mucosal lesions in cholestatic rats. Cholestasis was induced by surgical ligation
      of common bile duct and sham-operated rats served as control. Different groups of
      sham and cholestatic animals received solvent or pioglitazone (5, 15, 30 mg/kg)
      for 7 days. On the day eight rats were killed after oral ethanol administration
      and the area of gastric lesions was measured. The serums of rats were also
      collected to determine serum levels of tumour necrosis factor alpha (TNF-alpha),
      IL-1beta and bilirubin. The ethanol-induced gastric mucosal damage was
      significantly more severe in cholestatic rats than sham-operated ones.
      Pretreatment with pioglitazone dose-dependently attenuated gastric lesions
      induced by ethanol in both sham and cholestatic rats, but this effect was more
      prominent in cholestatic ones. The effect of pioglitazone was associated with a
      significant fall in serum levels of TNF-alpha in cholestatic rats. L-NAME, a non
      selective nitric oxide synthase (NOS) inhibitor, and decreased pioglitazone
      induced gastroprotective effect in cholestatic rats, while aminoguanidine, a
      selective inducible NOS inhibitor, potentiated pioglitazone-induced
      gastroprotective effect in the cholestatic rats. Chronic treatment with
      pioglitazone exerts an enhanced gastroprotective effect on the stomach ulcers of
      cholestatic rats compared to sham rats probably due to constitutive NOS induction
      and/or inducible NOS inhibition and attenuating release of TNF-alpha. 

PMID- 24456335
TI  - Differences in the clinical and angiographic characteristics of chronic total
      occlusion lesions in the three major coronary arteries.
AB  - OBJECTIVES: The purpose of this study was to evaluate the differences in the
      clinical and angiographic characteristics of chronic total occlusion (CTO)
      lesions among the 3 major coronary arteries (LAD, LCx, and RCA). BACKGROUND: The
      success rate of percutaneous coronary intervention (PCI) of CTO lesions is not
      uniform among the 3 major coronary arteries and this may be influenced by the
      differences in angiographic and clinical characteristics that may exists between
      them. METHODS: We retrospectively evaluated clinical and angiographic
      characteristics of patients who underwent PCI of CTO lesions at our 2 centers
      between 2003 and 2010. RESULTS: We analyzed 708 CTO-PCI procedures between 2003
      and 2010. The CTO lesions were located in LAD: 222 (31.4%), LCx: 167 (23.6%), and
      RCA: 319 (45.0%). Patients with CTO in LAD had lower incidence of previous
      history of PCI and CABG compared to those with CTO lesions in LCx or RCA. In
      regard to angiographic findings, LAD lesions tended to have more side branches
      and blunt occlusion stump. The LCx lesions presented more frequently as a part of
      multivessel disease. RCA lesions were significantly longer, more severely
      angulated, and calcified. Good collateral circulations were more often
      encountered in the RCA. In regard to success rates, RCA showed lower procedural
      success rates (71.8%) followed by LAD (74.8%) and LCx (79.0%). CONCLUSIONS: There
      were several differences in the clinical and angiographic characteristics of CTO
      lesions among the 3 major coronary arteries. These differences can explain the
      discrepancy in procedure success rates.

PMID- 24456336
TI  - Identification of plant metabolites of environmental contaminants by UPLC-QToF
      MS: the in vitro metabolism of triclosan in horseradish.
AB  - Plants can extensively transform contaminants after uptake through phase I and
      phase II metabolism to a large diversity of products. UPLC-QToF-MS was used to
      detect and identify metabolites of the bacteriostatic agent triclosan in a
      horseradish hairy root culture. Thirty-three metabolites of triclosan were
      recognized by a stepwise approach of mass defect filtering, multivariate data
      analysis, and isotope pattern filtering from a data set of several thousands of
      signals in the exposed culture. Structure proposals were elaborated for 23
      triclosan metabolites on the basis of their MS data. The majority were identified
      as conjugates (phase II metabolites) such as saccharides or sulfosaccharides.
      Additionally, a disulfosaccharide was identified as a plant metabolite for the
      first time. Besides that, also conjugates of a phase I metabolite,
      hydroxytriclosan, were determined in horseradish tissue extracts. Dehalogenation
      products of triclosan were not observed. The large number of metabolites detected
      and identified in this study emphasizes the importance of a comprehensive
      analytical approach in studies on the uptake and fate of organic contaminants in
      plants. 

PMID- 24456337
TI  - Transrectal negative pressure sponge treatment of full-thickness rectal
      perforation.

PMID- 24456338
TI  - Differential maturation of rhythmic clock gene expression during early
      development in medaka (Oryzias latipes).
AB  - One key challenge for the field of chronobiology is to identify how circadian
      clock function emerges during early embryonic development. Teleosts such as the
      zebrafish are ideal models for studying circadian clock ontogeny since the entire
      process of development occurs ex utero in an optically transparent chorion.
      Medaka (Oryzias latipes) represents another powerful fish model for exploring
      early clock function with, like the zebrafish, many tools available for detailed
      genetic analysis. However, to date there have been no reports documenting
      circadian clock gene expression during medaka development. Here we have
      characterized the expression of key clock genes in various developmental stages
      and in adult tissues of medaka. As previously reported for other fish, light dark
      cycles are required for the emergence of clock gene expression rhythms in this
      species. While rhythmic expression of per and cry genes is detected very early
      during development and seems to be light driven, rhythmic clock and bmal
      expression appears much later around hatching time. Furthermore, the maturation
      of clock function seems to correlate with the appearance of rhythmic expression
      of these positive elements of the clock feedback loop. By accelerating
      development through elevated temperatures or by artificially removing the
      chorion, we show an earlier onset of rhythmicity in clock and bmal expression.
      Thus, differential maturation of key elements of the medaka clock mechanism
      depends on the developmental stage and the presence of the chorion. 

PMID- 24456339
TI  - Effects of a carbohydrate-enriched night meal on sleepiness and sleep duration in
      night workers: a double-blind intervention.
AB  - The aim of this study was to investigate the effects of an intervention involving
      night meal composition on sleepiness and sleep duration in night security guards.
      A total of 54 male night security guards with a mean age of 30.8 years (SD = 5.5
      years) filled out a 24-h dietary recall and were submitted to anthropometric
      measurement. Twenty-four workers were assigned to the intervention. The
      intervention was carried out over three consecutive weeks under three conditions.
      On the first week, no change in workers' food composition was introduced. On the
      second week, the amount of carbohydrates was increased by 20-30% compared with
      the first week's intake, whereas during the third week protein intake was
      increased by 30-40% compared with baseline levels (first week). Throughout the
      study period, workers wore an actigraph device to estimate sleeping and waking
      times. A two-factor mixed model analysis with sleep duration as the outcome
      showed an interaction effect between body mass index (BMI) and condition (F2,56 =
      3.9; p = 0.03). Sleep duration was higher in obese workers compared with nonobese
      workers during the Carbohydrate condition (357 and 267 min, respectively). The
      analysis of variance (ANOVA) showed an increase in sleepiness under all
      conditions at 3:00 h (F1,276 = 165.73; p < 0.01) postprandially. A significant
      difference in sleepiness was also found between the obese and nonobese groups
      (F1,276 = 14.8; p < 0.01). The effect of the night meal content on sleep duration
      seems to be mediated by BMI. A carbohydrate-rich meal increased the duration of
      sleep in obese workers, and may therefore also influence sleepiness.

PMID- 24456340
TI  - Risk factors for second primary neoplasia of esophagus in newly diagnosed head
      and neck cancer patients: a case-control study.
AB  - BACKGROUND: The prevalence of esophageal neoplasia in head and neck (H&N) cancer
      patients is not low; however, routine esophageal surveillance is not included in
      staging of newly-diagnosed H&N cancers. We aimed to investigate the risk factors
      for synchronous esophageal neoplasia and the impact of endoscopy on management of
      H&N cancer patients. METHODS: A total of 129 newly diagnosed H&N cancer patients
      who underwent endoscopy with white-light imaging, narrow-band imaging (NBI) with
      magnifying endoscopy (ME), and chromoendoscopy with 1.5% Lugol's solution, before
      definite treatment were enrolled prospectively. RESULTS: 60 esophageal lesions
      were biopsied from 53 (41.1%) patients, including 11 low-grade, 14 high-grade
      intraepithelial neoplasia and 12 invasive carcinoma in 30 (23.3%) patients.
      Alcohol consumption [odds ratio (OR) 5.90, 95% confidence interval (CI) 1.23
      26.44], advanced stage (stage III and IV) of index H&N cancers (OR 2.98, 95% CI
      1.11-7.99), and lower body mass index (BMI) (every 1-kg/m2 increment with OR
      0.87, 95% CI 0.76-0.99) were independent risk factors for synchronous esophageal
      neoplasia. NBI with ME was the ideal screening tool (sensitivity, specificity,
      and accuracy of 97.3%, 94.1%, and 96.3%, respectively, for detection of
      dysplastic and cancerous esophageal lesions). The treatment strategy was modified
      after endoscopy in 20 (15.5%) patients. The number needed to screen was 6.45 (95%
      CI 4.60-10.90). CONCLUSIONS: NBI-ME surveillance of esophagus should be done in
      newly-diagnosed H&N cancer patients, especially those with alcohol drinking,
      lower BMI, and advanced stage of primary tumor.

PMID- 24456342
TI  - Insight into the capacitive properties of reduced graphene oxide.
AB  - Graphene-based materials have been widely used as electrode materials of
      supercapacitors. However, the intrinsic properties related to the capacitance of
      graphene-based materials essentially need to be clarified. In this work, we have
      prepared reduced graphene oxide (RGO) through a simple chemical reduction
      strategy by using hydrazine hydrate as the reducing reagent. The different
      reduction levels of graphene sheets were successfully realized by controlling the
      chemical reduction time, and the surface state and density of the functional
      group were precisely adjusted. We investigated the electrochemical performance of
      the as-prepared RGO electrode materials. A time dependence of the specific
      capacitance for the as-prepared RGO electrode was observed. Graphene oxide
      reduced by hydrazine hydrate at 95  degrees C for 60 min exhibited the highest
      weight specific capacitance. The RGO samples were systematically characterized
      with Fourier transform infrared (FTIR) spectra, X-ray photoelectron spectroscopy
      (XPS), and Raman measurements. We conclude that the oxygen-containing groups,
      electrical conductivity, density of defects, and carbon electronic state play
      substantial roles in deciding the specific capacitance of reduced graphene oxide.

PMID- 24456341
TI  - Bacillus thuringiensis Cry1A toxins are versatile proteins with multiple modes of
      action: two distinct pre-pores are involved in toxicity.
AB  - Cry proteins from Bacillus thuringiensis are insecticidal PFTs (pore-forming
      toxins). In the present study, we show that two distinct functional pre-pores of
      Cry1Ab are formed after binding of the protoxin or the protease-activated toxin
      to the cadherin receptor, but before membrane insertion. Both pre-pores actively
      induce pore formation, although with different characteristics, and contribute to
      the insecticidal activity. We also analysed the oligomerization of the mutant
      Cry1AbMod protein. This mutant kills different insect populations that are
      resistant to Cry toxins, but lost potency against susceptible insects. We found
      that the Cry1AbMod-protoxin efficiently induces oligomerization, but not the
      activated Cry1AbMod-toxin, explaining the loss of potency of Cry1AbMod against
      susceptible insects. These data are relevant for the future control of insects
      resistant to Cry proteins. Our data support the pore-formation model involving
      sequential interaction with different midgut proteins, leading to pore formation
      in the target membrane. We propose that not only different insect targets could
      have different receptors, but also different midgut proteases that would
      influence the rate of protoxin/toxin activation. It is possible that the two pre
      pore structures could have been selected for in evolution, since they have
      differential roles in toxicity against selected targets, increasing their range
      of action. These data assign a functional role for the protoxin fragment of Cry
      PFTs that was not understood previously. Most PFTs produced by other bacteria are
      secreted as protoxins that require activation before oligomerization, to finally
      form a pore. Thus different pre-pores could be also part of the general mechanism
      of action of other PFTs. 

PMID- 24456343
TI  - Drive for muscularity is heightened in body-dissatisfied men who socially
      compare.
AB  - Men's drive for muscularity refers to the degree to which men wish to increase
      their muscularity. Men who are more extreme in their drive for muscularity face
      dangerous consequences, such as increased levels of eating pathology and use of
      performance-enhancing substances. The aim of this study was to predict men's
      drive for muscularity, and to test whether hypothesized predictive factors vary
      across age groups. Participants were 226 men ages 18-67. It was hypothesized that
      body dissatisfaction would predict men's drive for muscularity. More
      substantively, however, it was hypothesized that having a strong tendency to
      compare oneself with others would exacerbate the relationship between men's body
      dissatisfaction and their drive for muscularity. Results of a hierarchical
      multiple regression analysis supported these hypotheses. Furthermore, this
      exacerbating effect was present regardless of men's age. Implications for
      assessment, clinical practice, research, and prevention efforts are discussed. 

PMID- 24456344
TI  - Specific turion yields of different clones of Spirodela polyrhiza depend on
      external phosphate thresholds.
AB  - Turions play an important role in the survival strategy of the duckweed Spirodela
      polyrhiza. Therefore, factors influencing the formation of these survival organs
      were studied. Phosphate deficiency is the main natural factor inducing turion
      formation and the specific turion yield (SY), i.e. the number of turions formed
      per frond, varied widely for five different clones from different climate zones.
      The concentrations of phosphate and nitrate in the nutrient media were
      investigated at the onset of turion formation, with SY ranging from 0.22 to 5.9.
      Tissue P and N content was also investigated in vegetative fronds at the onset of
      turion formation and in newly formed turions. The clones were selected to test
      possible correlations between SY and threshold nutrient concentration for turion
      formation. Only one correlation, between SY and external phosphate concentration,
      was significant: clones with high SY started turion formation at higher external
      phosphate concentrations. Turion formation is thus mainly induced by the external
      phosphate concentration, below a defined, clone-dependent threshold. We propose
      the following mechanism: a switch of the developmental programme of frond
      primordia from vegetative frond to turion formation at a higher phosphate
      threshold saves more phosphate for turion formation instead of using it for a
      further vegetative growth. However, the period of growth preceding turion
      formation does not depend on this threshold value, but rather on the growth rate
      of the vegetative fronds, which actually produce the phosphate shortage by taking
      it up from the surrounding medium.

PMID- 24456346
TI  - Effects of boiling on chlorogenic acid and the liver protective effects of its
      main products against CCl4-induced toxicity in vitro.
AB  - Chlorogenic acid (3-O-caffeoylquinic acid, CA) is the active component in several
      botanical beverage, vegetables, fruits, and herbal drugs. The effect of water
      boiling on the bioactivity of CA was studied. CA could be isomerized to 4-O
      caffeoylquinic acid (4-O-CA) and 5-O-caffeoylquinic acid (5-O-CA) in decoctive
      extraction, and each of the isomers occupied about one-third of the total
      caffeoylquinic acids. A novel method, using water elution of microsphere resin,
      was used to purify CA and its 2 isomers. The yield of CA, 4-O-CA, and 5-O-CA was
      82%, 5.6%, and 50%, with the purity of 98%, 97%, and 99%, respectively. The DPPH
      radical scavenging assay showed that 4-O-CA, 5-O-CA, and CA exhibited similar
      activity. However, there was no significant difference between 4-O-CA and 5-O-CA
      when used against CCl4-induced toxicity in hepG2 cells. Our studies show that
      isomerization is the main transformation of CA in boiling, and the decoction
      could not decrease the anti-oxidant activity of CA.

PMID- 24456347
TI  - Personality and cardiovascular risk: association between hypertension and
      affective temperaments-a cross-sectional observational study in primary care
      settings.
AB  - BACKGROUND: Affective temperaments can be considered the subclinical
      manifestations of affective disorders, which have a bidirectional relationship
      with cardiovascular diseases. OBJECTIVES: Aim of this study was to assess the
      role of affective temperaments in primary hypertension, which is the leading risk
      factor of cardiovascular morbidity and mortality. METHODS: In total, 251
      consecutive patients, including 179 patients being treated for primary
      hypertension with anti-hypertensives, with chronic disorders without diagnosed
      depression were enrolled in a primary care setting. Patients completed the
      Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire
      (TEMPS-A). Lifestyle-related risk factors, chronic diseases including
      cardiovascular complications were also recorded. Logistic regression analysis was
      used to determine the relationship of affective temperaments and lifestyle
      related risk factors on hypertension. RESULTS: Dominant cyclothymic temperament
      with instability and rapid mood swings as main characteristics-had a significant
      association with hypertension (P = 0.006) even after the adjustment of
      correlation for known risk factors such as age, diabetes mellitus and obesity
      (OR: 11.88, 95%CI: 1.27-111.17). This association remained significant after
      controlling for the family wise error rate. The obtained adjusted P value was
      0.024 at a 0.05 error rate. CONCLUSION: RESULTS indicate that dominant
      cyclothymic affective temperament may be an additional risk factor in
      cardiovascular morbidity, and it may be worthy of further assessment to identify
      patients at risk and formulate a more individualized treatment approach.

PMID- 24456348
TI  - Evidence-based primary care treatment guidelines for skin infections in Europe: a
      comparative analysis.
AB  - BACKGROUND: In Europe, most antibiotics for human use are prescribed in primary
      care. Incorporating resistance data into treatment guidelines could improve
      appropriate prescribing, increase treatment effectiveness and control the
      development of resistance. OBJECTIVES: This study reviews primary care treatment
      guidelines for bacterial skin infections across Europe and assesses to what
      extent they are based on antibiotic resistance data. METHODS: Thirteen primary
      care treatment guidelines were obtained from eight countries across Europe. Both
      the treatment recommendations and the underlying evidence were assessed. The
      class and dose of recommended antibiotics were investigated and compared using
      the World Health Organisation's standardized volume of Defined Daily Dose.
      Furthermore, analysis investigated whether guidelines included references to
      scientific publications about antibiotic resistance data, and whether these were
      of national origin. RESULTS: Guidelines were included regarding common skin
      infections in primary care: Impetigo, Cellulitis, Erysipelas, Folliculitis and
      Furuncle. RESULTS showed a high agreement across Europe: all recommended
      antibiotics are of the beta-lactam class and mainly in the small spectrum. The
      advised treatment durations are consistent; the dosages, however, vary
      considerably, with the highest dosages recommended in Sweden. Seven guidelines
      (54%) did not include scientific references related to resistance. CONCLUSION:
      There may be a lack of relevant national data on resistance. This study
      highlights the need to collect more national resistance data (particularly
      regarding beta-lactams) to create stronger evidence-based treatment guidelines
      for skin infections in Europe.

PMID- 24456349
TI  - Preserving the legacy of healthy Korean food.

PMID- 24456350
TI  - Health benefits of kimchi (Korean fermented vegetables) as a probiotic food.
AB  - Kimchi is a traditional Korean food manufactured by fermenting vegetables with
      probiotic lactic acid bacteria (LAB). Many bacteria are involved in the
      fermentation of kimchi, but LAB become dominant while the putrefactive bacteria
      are suppressed during salting of baechu cabbage and the fermentation. The
      addition of other subingredients and formation of fermentation byproducts of LAB
      promote the fermentation process of LAB to eventually lead to eradication of
      putrefactive- and pathogenic bacteria, and also increase the functionalities of
      kimchi. Accordingly, kimchi can be considered a vegetable probiotic food that
      contributes health benefits in a similar manner as yogurt as a dairy probiotic
      food. Further, the major ingredients of kimchi are cruciferous vegetables; and
      other healthy functional foods such as garlic, ginger, red pepper powder, and so
      on are added to kimchi as subingredients. As all of these ingredients undergo
      fermentation by LAB, kimchi is regarded as a source of LAB; and the fermentative
      byproducts from the functional ingredients significantly boost its functionality.
      Because kimchi is both tasty and highly functional, it is typically served with
      steamed rice at every Korean meal. Health functionality of kimchi, based upon our
      research and that of other, includes anticancer, antiobesity, anticonstipation,
      colorectal health promotion, probiotic properties, cholesterol reduction,
      fibrolytic effect, antioxidative and antiaging properties, brain health
      promotion, immune promotion, and skin health promotion. In this review we
      describe the method of kimchi manufacture, fermentation, health functionalities
      of kimchi and the probiotic properties of its LAB.

PMID- 24456351
TI  - Korean traditional natural herbs and plants as immune enhancing, antidiabetic,
      chemopreventive, and antioxidative agents: a narrative review and perspective.
AB  - The world is becoming increasingly interested in Korean food and its ingredients.
      The attention goes beyond the typical examples, such as kimchi and fermented
      sauces; peculiar food ingredients that are widely consumed in Korea are now
      entering the world's functional food markets. This trend was supported by
      scientific research, and this review seeks to combine and summarize the findings
      of the past 10 years. The results are organized into four groups depending on
      whether the ingredient strengthens the immune system, has antidiabetic effects,
      has chemopreventive effects, or has an antioxidative effects. We would also like
      to point out that this review only covers the topic of Korean traditional plants
      and herbs. After the summary of research findings, we discuss challenges and
      opportunities, exploring the direction of future research and the potential of
      Korean traditional food ingredients in food industry and markets.

PMID- 24456352
TI  - Omija fruit extract improves endurance and energy metabolism by upregulating PGC
      1alpha expression in the skeletal muscle of exercised rats.
AB  - This study was conducted to examine the effects of omija fruit extract on the
      endurance and energy metabolism of rats trained under a progressive loaded
      exercise program. Thirty male Sprague-Dawley rats (6 weeks old) were divided into
      three groups according to exercise and experimental diets for 6 weeks: the
      sedentary control (SC) group (n=10), the exercise control (EC) group (n=10), and
      the exercise group supplemented with 0.6% w/w omija extract (OM; n=10). The omija
      supplement significantly extended the running endurance time compared with the EC
      group. The soleus muscle weight was significantly higher in the OM group compared
      with the EC group and the plasma lactate and ammonia levels were significantly
      lower in the OM group than in the EC group. Plasma glucose, free fatty acid, and
      gastrocnemius muscle glycogen concentrations were also significantly lower in the
      OM group compared with the EC group. The lactate dehydrogenase activity was
      significantly higher in the gastrocnemius muscle of the OM group compared with
      the EC group. Expression of the peroxisome proliferator-activated receptor gamma
      coactivator-1alpha (PGC-1alpha) mRNA in the gastrocnemius muscle and soleus
      muscle were significantly elevated in the OM group and the soleus muscle
      peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine
      palmitoyltransferase 1b (CPT1b), and beta-hydroxyacyl coenzyme A dehydrogenase
      (beta-HAD) mRNA expressions showed the same tendency. Taken together, these
      results show that supplementation of omija fruit extract enhances endurance and
      energy metabolism by upregulating the PGC-1alpha expression in the skeletal
      muscle.

PMID- 24456353
TI  - Cooked rice inhibits hepatic fat accumulation by regulating lipid metabolism
      related gene expression in mice fed a high-fat diet.
AB  - Although rice has been shown to have beneficial health effects, little is known
      about the effect of rice on hepatic lipid accumulation as a carbohydrate source.
      This study investigated the effects and mechanism of action of cooked rice on
      high-fat diet (HF)-induced fat accumulation. The C57BL/6 mice were divided into
      three groups and fed a normal diet (NOR), HF, or HF with cooked rice (HF-CR) for
      12 weeks. The HF-CR-fed mice had significantly lower body weight gains and
      abdominal fat mass compared with the HF-fed mice. Consuming cooked rice resulted
      in significantly lower serum total cholesterol, low-density lipoprotein
      cholesterol, hepatic lipid content, and lipid droplet number and size. Cooked
      rice consumption also suppressed the HF-induced increase in expression of
      lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c),
      fatty acid synthase (FAS), stearoyl CoA desaturase 1 (SCD-1), peroxisome
      proliferator-activated receptor gamma (PPARgamma), and CD36. The expression of
      cholesterol metabolism-related genes, such as acyl-CoA:cholesterol
      acyltransferase 1 (ACAT1), were also downregulated in the HF-CR-fed mice. Cooked
      rice may prevent HF-induced fat accumulation by regulating lipid metabolism
      related gene expression, and it may be a useful carbohydrate source for
      preventing nonalcoholic fatty liver disease.

PMID- 24456354
TI  - The traditional Korean dietary pattern is associated with decreased risk of
      metabolic syndrome: findings from the Korean National Health and Nutrition
      Examination Survey, 1998-2009.
AB  - The traditional Korean diet has several healthy components, including abundant
      vegetables, fermented foods, a variety of foodstuffs, and a balance of animal and
      vegetable food intake. Although the traditional Korean diet has many healthy
      components, few studies have been conducted on the health advantages of the
      Korean dietary pattern. This study is intended to clarify the relationship
      between Korean dietary patterns and chronic diseases using the Integrated Korean
      Dietary Pattern Score (I-KDPS). I-KDPS is an index for measuring Korean dietary
      patterns based on traditional Korean meals and reflects the complex and
      multifaceted characteristics of Korean food culture. I-KDPS is composed of seven
      items to measure the level of balance and adequacy of Korean food consumption,
      with a maximum score of 60. When I-KDPS was applied to the Korean National Health
      and Nutrition Examination Survey (1998-2009), a nationwide survey, I-KDPS was
      closely related to the risk of metabolic syndrome. Even though there were a few
      differences among the years surveyed, the risk of metabolic syndrome, obesity,
      hypertension, and hypertriglyceridemia significantly decreased as I-KDPS
      increased. These results indicate that risk of diseases, including metabolic
      syndrome, decreases in individuals adhering to traditional Korean dietary
      patterns in adequate levels and those who eat a balanced diet. The result of this
      study shows that the traditional Korean table setting, which comprises side
      dishes, including seasoned vegetables, grilled dishes, and fermented products
      with cooked rice (bap), soup (guk), and kimchi, contains traits that help prevent
      metabolic syndrome. I-KDPS coupled with the basic study of the healthfulness of
      the Korean dietary lifestyle is expected to help establish a foundation for
      continuous development of health promoting Korean foods and dietary culture.

PMID- 24456355
TI  - Superiority of traditional cooking process for bugak (Korean traditional fried
      dish) for plasma lipid reduction.
AB  - In this study, the efficacy and mode of action of the Korean traditional fried
      dish bugak for reducing plasma lipids are investigated. Three different studies
      were performed as follows: lipid-lowering effects of bugak compared with (1)
      different preparation methods, (2) different batters, and (3) different frying
      oils. Traditionally, bugak is prepared with fermented glutinous rice batter (FGR)
      and pan-fried in unroasted sesame oil (USSO; this preparation of bugak is
      referred to as FGRUSSO). FGR is prepared by placing the glutinous rice and water
      in a crock for 7 days at room temperature. For the study, wheat flour batter (WF)
      and soybean oil (SBO) were alternatively used. Low-density lipoprotein receptor
      knockout (LDLr-/-) mice (n=24) were fed atherogenic diets with bugak (20 g/100 g
      of feed) for 10 weeks. Plasma triglyceride (TG), total cholesterol (TC), and low
      density lipoprotein cholesterol (LDL-C) concentration and hepatic lipid
      accumulations decreased significantly in mice fed FGRUSSO, compared with bugak
      made with WF and fried in SBO (WFSBO). Protein expression of fatty acid synthesis
      (FAS) and 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMGCR) in the FGRUSSO
      group was decreased, although sterol regulatory element-binding proteins (SREBP-1
      and -2) were not different. When batter differences were compared, TG
      concentration of mice fed bugak prepared with FGR and fried in SBO (FGRSBO) was
      lower than the WFSBO group due to suppression of hepatic FAS expression. In the
      oil comparison study, TC and LDL-C concentrations in the FGRUSSO group were lower
      due to attenuated HMGCR activity. In conclusion, bugak prepared by traditional
      cooking methods was most effective for lowering plasma TG, TC, and LDL-C via
      suppressing hepatic FAS and HMGCR activity, although transcription factors for
      regulating lipogenic enzyme expression were not significantly different.

PMID- 24456356
TI  - Doenjang, a fermented Korean soybean paste, inhibits lipopolysaccharide
      production of gut microbiota in mice.
AB  - Doenjang has been reported to exhibit antioxidant, fibrinolytic, antimutagenic,
      anticancer, and antiobesity effects. In our preliminary study, doenjang decreased
      fecal lipopolysaccharide (LPS) levels in mice. Therefore, we investigated the
      effect of doenjang on the composition of gut microbiota in mice. Treatment with
      doenjang significantly increased the number of bifidobacteria cultured in BL
      media, compared with mice not treated with doenjang. However, doenjang decreased
      the number of Enterobacteriaceae cultured in DHL media. Doenjang significantly
      suppressed the beta-glucuronidase activity, but did not influence alpha-/beta
      glucosaminidase and alpha-/beta-glucosidase activities. When gut microbiota in
      mice treated with or without doenjang was analyzed by pyrosequencing, doenjang
      induced a significant modulation of the populations of the dominant gut
      microbiota. At the phylum level, doenjang treatment resulted in a significant
      decrease of Firmicutes and an increase of Bacteroidetes, which led to a decrease
      in the Firmicutes to Bacteroidetes ratio in gut microbiota. At the family level,
      the number of Ruminococcaceae and Lachnospiraceae were significantly decreased,
      while the number of Odoribacter_f was increased in doenjang-treated mice. Of
      colonic tight junction proteins, occludin, ZO-1, and claudin-1 in mice, occludin
      alone was significantly increased by treatment with doenjang. Although treatment
      with doenjang seemed to suppress NF-kappaB activation, it was not significant.
      Doenjang significantly suppressed tumor necrosis factor-alpha expression, whereas
      it did not influence interleukin (IL)-1beta and IL-6 expression. However,
      doenjang increased IL-10 expression. Based on these findings, doenjang may
      promote gut health by regulating gut microbiota and its LPS concentrations and
      suppressing harmful enzyme production.

PMID- 24456357
TI  - Laminaria japonica combined with probiotics improves intestinal microbiota: a
      randomized clinical trial.
AB  - Laminaria japonica--a widely used ingredient in seaweed kimchi--and lactic acid
      bacteria (LAB)--a main component of traditional fermented Korean food--may alter
      human intestinal microbiota composition and have a positive effect on various
      digestive problems. However, few clinical trials have investigated the potential
      benefits of L. japonica when combined with LAB for human intestinal microbiota.
      Therefore, this study was designed to evaluate the effects of L. japonica and
      representative LAB on the human intestine. Forty participants with no known
      digestive diseases were randomly assigned to one of the two combination groups:
      (1) L. japonica with LAB and (2) L. japonica with placebo LAB. The study agents
      were administered for 4 weeks with a 2-week follow-up period. The primary outcome
      measure was the number of each of the seven LAB species in the human intestine,
      and the secondary outcome measures included the Korean version of the
      Gastrointestinal Symptom Rating Scale, the World Health Organization Quality of
      Life, and bowel functions. The primary outcome was evaluated before and after
      administration of the study agents (0 and 4 weeks), and the secondary outcomes
      were evaluated at 0, 4, and 6 weeks. Four of the seven LAB species were found to
      be significantly increased in the L. japonica with the LAB group and five species
      were significantly different from those of the placebo group. The secondary
      outcome measures did not change significantly. In conclusion, L. japonica with
      LAB facilitated the proliferation of beneficial human intestinal microbiota. (
      TRIAL NUMBER: ClinicalTrials.gov NCT01651741).

PMID- 24456358
TI  - Black soybean extract protects against TMT-induced cognitive defects in mice.
AB  - To find a neuroactive compound with a potent inhibitory effect on
      acetylcholinesterase (AChE) and in vivo anti-amnesic activity from natural
      resources, we evaluated anthocyanins and nonanthocyanins from black soybean
      extract. Nonanthocyanins from black soybean extract were the most potent and dose
      dependent AChE inhibitors. Intracellular reactive oxygen species accumulation
      resulting from H2O2 treatment was significantly decreased compared with cells
      treated with H2O2 only. Nonanthocyanins were also neuroprotective against H2O2
      treated neurotoxicity by 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium
      bromide (MTT) and lactate dehydrogenase (LDH) assay. Finally, nonanthocyanins
      from black soybean in the preadministration group attenuated trimethyltin (TMT)
      induced memory injury in both in vivo tests. AChE, prepared from mice brain
      tissues, was inhibited by nonanthocyanins from black soybean in a dose-dependent
      manner. Malondialdehyde generation in the brain homogenates of mice treated with
      nonanthocyanins from black soybean was decreased. We concluded that
      nonanthocyanins from black soybean had an efficacious in vitro AChE inhibitory
      activity, and protected against H2O2-induced neurotoxicity. In addition, our
      findings suggest that nonanthocyanins from black soybean may improve the TMT
      induced learning and memory deficit because of AChE inhibition of mice brain
      tissue. Consequently, these results demonstrate that the nonanthocyanins from
      black soybean could possess a wide range of beneficial activities for
      neurodegenerative disorders.

PMID- 24456359
TI  - Anti-allergic action of aged black garlic extract in RBL-2H3 cells and passive
      cutaneous anaphylaxis reaction in mice.
AB  - Garlic (Allium sativum) has been used as a food as well as a component of
      traditional medicine. Aged black garlic (ABG) is known to have various
      bioactivities. However, the effect of ABG on allergic response is almost unknown.
      In the present study, we investigated whether ABG can inhibit immunoglobulin E
      mediated allergic response in RBL-2H3 cells as well as in vivo passive cutaneous
      anaphylaxis (PCA). In in vitro tests, ethyl acetate extract (EBG) of ABG
      significantly inhibited the release of beta-hexosaminidase (IC50, 1.53 mg/mL) and
      TNF-alpha (IC50, 0.98 mg/mL). Moreover, BG10, an active fraction of EBG,
      dramatically suppressed the release of beta-hexosaminidase (IC50, 53.60 MUg/mL)
      and TNF-alpha (IC50, 27.80 MUg/mL). In addition, BG10 completely blocked the
      formation of prostaglandin E2 and leukotriene B4 at >=25 MUg/mL. When the effect
      of BG10 on FcERI receptor cascade was investigated, BG10 significantly inhibited
      the phosphorylation of Syk, but not Lyn. Furthermore, BG10 dose dependently
      decreased the phosphorylation of cytosolic phospholipase A2 (cPLA2) and 5
      lipoxygenase (5-LO) as well as the expression of cyclooxygenase-2 (COX-2).
      Consistent with what has been mentioned earlier, BG10 also significantly
      inhibited the PCA reaction in mice. In conclusion, these results indicate that
      ABG suppresses the allergic response, and the mechanism for its anti-allergic
      action may involve suppressions of Syk, cPLA2, 5-LO, and COX-2. The anti-allergic
      actions of ABG, EBG, or BG10 suggest that they may be useful as functional foods
      for allergic diseases.

PMID- 24456360
TI  - Schisandra chinensis prevents alcohol-induced fatty liver disease in rats.
AB  - Schisandra chinensis (SC), a traditional herbal medicine, has been prescribed for
      patients suffering from various liver diseases, including hepatic cancer,
      hypercholesterolemia, and CCl4-induced liver injury. We investigated whether SC
      extract has a protective effect on alcohol-induced fatty liver and studied its
      underlying mechanisms. Rats were fed with ethanol by intragastric administration
      every day for 5 weeks to induce alcoholic fatty liver. Ethanol treatment resulted
      in a significant increase in alanine aminotransferase, aspartate
      aminotransferase, and hepatic triglyceride (TG) levels and caused fatty
      degeneration of liver. Ethanol administration also elevated serum TG and total
      cholesterol (TC) and decreased high-density lipoprotein (HDL) cholesterol levels.
      However, after administration of ethanol plus SC extracts, the ethanol-induced
      elevation in liver TC and TG levels was reversed. Elevation in serum TG was not
      observed after treatment with SC. Moreover, compared with the ethanol-fed group,
      the rats administered ethanol along with SC extracts for 5 weeks showed
      attenuated fatty degeneration and an altered lipid profile with decreased serum
      TC and TG, and increased HDL cholesterol levels. Chronic ethanol consumption did
      not affect peroxisome proliferator-activated receptor gamma (PPARgamma) levels,
      but it decreased PPARalpha and phospho-AMP-activated protein kinase (AMPK) levels
      in the liver. However, SC prevented the ethanol-induced decrease in PPARalpha
      expression and induced a significant decrease in sterol regulatory element
      binding protein-1 expression and increase in phospho-AMPK expression in rats with
      alcoholic fatty liver. SC administration resulted in a significant decrease in
      intracellular lipid accumulation in hepatocytes along with a decrease in serum TG
      levels, and it reversed fatty liver to normal conditions, as measured by
      biochemical and histological analyses. Our results indicate that the protective
      effect of SC is accompanied by a significant increase in phospho-AMPK and
      PPARalpha expression in hepatic tissue of alcoholic rats, thereby suggesting that
      SC has the ability to prevent ethanol-induced fatty liver, possibly through
      activation of AMPK and PPARalpha signaling.

PMID- 24456361
TI  - Red ginseng (Panax ginseng) decreases isoproterenol-induced cardiac injury via
      antioxidant properties in porcine.
AB  - Red ginseng (RG, Panax ginseng) has been shown to possess various ginsenosides.
      These ginsenosides are widely used for treating cardiovascular diseases in Asian
      communities. The present study was designed to evaluate the cardioprotective
      potential of RG against isoproterenol (ISO)-induced myocardial infarction (MI),
      by assessing electrocardiographic, hemodynamic, and biochemical parameters. Male
      porcines were orally administered with RG (250 and 500 mg/kg) or with vehicle for
      9 days, with concurrent intraperitoneal injections of ISO (20 mg/kg) on the 8th
      and 9th day. RG significantly attenuated ISO-induced cardiac dysfunctions as
      evidenced by improved ventricular hemodynamic functions and reduced ST segment
      and QRS complex intervals. Also, RG significantly ameliorated myocardial injury
      parameters such as antioxidants. Malonaldialdehyde formation was also inhibited
      by RG. Based on the results, it is concluded that RG possesses significant
      cardioprotective potential through the inhibition of oxidative stress and may
      serve as an adjunct in the treatment and prophylaxis of MI.

PMID- 24456362
TI  - Doenjang, a Korean fermented soy food, exerts antiobesity and antioxidative
      activities in overweight subjects with the PPAR-gamma2 C1431T polymorphism: 12
      week, double-blind randomized clinical trial.
AB  - We examined the antiobesity and antioxidant effects of supplementation with
      doenjang, a fermented soybean paste, in overweight Koreans with the PPAR-gamma2
      C1431T polymorphism. Sixty overweight subjects were randomly assigned to consume
      either 9.8 g/day of doenjang or placebo for 12 weeks. Before and after the
      intervention, anthropometric and metabolic parameters, along with abdominal fat
      distribution and PPAR-gamma2 polymorphisms, were measured. Fifty-one subjects
      completed the study, doenjang (n=26) and placebo (n=25) groups. Relative
      frequencies of the PPAR-gamma2 genotypes CC, TC, and TT were 70% (n=41), 25.9%
      (15), and 3.4% (2), whereas those of the PPAR-gamma2 alleles C and T were 81.6%
      and 18.4%. Visceral fat area (VFA) was significantly decreased by doenjang
      supplementation in subjects with a mutant T allele of PPAR-gamma2 compared to
      those with a C allele after adjusting for age, sex, and body mass index. Plasma
      free fatty acid, insulin, and homeostatic model assessment insulin resistance
      (HOMA-IR) levels were also significantly increased in the doenjang group.
      Doenjang pills significantly activated radical clearance capacity (ORAC and DNA
      tail length) in subjects with the C allele. The catalase (CAT) activity was
      increased twofold in the doenjang-treated group with the C allele, but this
      phenomenon was reversed in those with the T allele. Doenjang-treated subjects
      tended to have low dietary carbohydrate and sodium intakes compared with those
      given placebo. We found that doenjang supplementation decreased visceral fat
      accumulation and aging most effectively in subjects with PPAR-gamma
      polymorphisms. This study suggests that doenjang has antiobesity and
      antioxidative effects in overweight individuals with mutant alleles of PPAR
      gamma2.

PMID- 24456363
TI  - Korean red ginseng improves glucose control in subjects with impaired fasting
      glucose, impaired glucose tolerance, or newly diagnosed type 2 diabetes mellitus.
AB  - This study was designed to evaluate the effect of Korean red ginseng (KRG)
      supplementation on glucose control in subjects with impaired fasting glucose
      (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes
      mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo
      controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose
      related biomarkers, including serum and whole blood levels of glucose, insulin,
      and C-peptide, were measured by 2-h oral glucose tolerance tests (OGTTs) at
      baseline and after the 12-week intervention. After the intervention, the test
      group showed a significant decrease in serum levels of glucose at 30 min (
      22.24+/-10.77 mg/dL) and whole blood levels of glucose at 30 min (-17.52+/-5.22
      mg/dL). In addition, the test group tended to have lower whole blood levels of
      glucose at 0 min and glucose area under curve (AUC). However, the placebo group
      did not show any changes in blood glucose-related indices. The changes
      (difference from baseline) in serum glucose levels at 30 min, whole blood glucose
      levels at 60 min, and glucose AUC during OGTTs in the test group exhibited a
      tendency toward a decrease from those in the placebo group. There were
      significant decreases or trends toward a decrease in both serum insulin and C
      peptide concentrations at most time intervals in the test group. In conclusion,
      KRG supplementation (5 g/day) may be beneficial for controlling serum and whole
      blood glucose levels compared with placebo among patients with IFG, IGT, or T2DM.

PMID- 24456364
TI  - Soybean extracts facilitate bacterial agglutination and prevent biofilm formation
      on orthodontic wire.
AB  - Soybean is an essential food ingredient that contains a class of organic
      compounds known as isoflavones. It is also well known that several plant
      agglutinins interfere with bacterial adherence to smooth surfaces. However,
      little is known about the effects of soybean extracts or genistein (a purified
      isoflavone from soybean) on bacterial biofilm formation. We evaluated the effects
      of soybean (Glycine max) extracts, including fermented soybean and genistein, on
      streptococcal agglutination and attachment onto stainless steel orthodontic wire.
      After cultivating streptococci in biofilm medium containing soybean extracts and
      orthodontic wire, the viable bacteria attached to the wire were counted. Phase
      contrast microscopy and scanning electron microscopy (SEM) analyses were
      conducted to evaluate bacterial agglutination and attachment. Our study showed
      that soybean extracts induce agglutination between streptococci, which results in
      bacterial precipitation. Conversely, viable bacterial counting and SEM image
      analysis of Streptococcus mutans attached to the orthodontic wire show that
      bacterial attachment decreases significantly when soybean extracts were added.
      However, there was no significant change in pre-attached S. mutans biofilm in
      response to soybean. A possible explanation for these results is that increased
      agglutination of planktonic streptococci by soybean extracts results in
      inhibition of bacterial attachment onto the orthodontic wire.

PMID- 24456365
TI  - Cheonggukjang ethanol extracts inhibit a murine allergic asthma via suppression
      of mast cell-dependent anaphylactic reactions.
AB  - Cheonggukjang (CGJ), a traditional Korean fermented soybean food, exerts
      immunomodulatory effects. Asthma is the most common chronic allergic disease to
      be associated with immune response to environmental allergens. In the
      pathogenesis of asthma, histamine is one of the important inflammatory mediators
      released from granules of mast cells. In this study, we evaluated the therapeutic
      effect of CGJ on a mouse model of ovalbumin (OVA)-induced asthma via the
      suppression of histamine release. C57BL/6 mice were sensitized by intraperitoneal
      injection of OVA or a phosphate-buffered saline (PBS) control and then challenged
      with OVA inhalation. Mice were treated intraperitoneally with either 70% ethanol
      extracted CGJ (CGJE) (100 mg/kg/day) or equivalent PBS. Asthma-related
      inflammation was assessed by bronchoalveolar lavage fluid cell counts and
      histopathological and immunohistochemical analysis of lung tissues. To elucidate
      the mechanisms of asthma inhibition by CGJE treatment, we also examined
      degranulation and histamine release of compound 48/80-induced rat peritoneal mast
      cells (RPMCs). Treatment with CGJE downregulated the number of eosinophils and
      monocytes in the lungs of mice challenged with OVA and suppressed
      histopathological changes, such as eosinophil infiltration, mucus accumulation,
      goblet cell hyperplasia, and collagen fiber deposits. Moreover, CGJE alleviated
      compound 48/80-induced mast cell degranulation and histamine release from RPMCs
      through inhibition of calcium (Ca2+) uptake as well as ear swelling by
      infiltration of inflammatory cells. These findings demonstrated that CGJE can be
      used as an antiasthmatic dietary supplements candidate for histamine-mediated
      asthma.

PMID- 24456366
TI  - Immunological activity of ginseng is enhanced by solid-state culture with
      Ganoderma lucidum mycelium.
AB  - Fresh ginseng was fermented with Ganoderma lucidum mycelium (GL) in solid-state
      culture to enhance its immunomodulatory activity. When crude polysaccharide (FG
      GL-CP) was fractionated from lyophilized fermented ginseng (FG-GL), FG-GL-CP
      showed significantly higher mitogenic, macrophage stimulating, and intestinal
      immune system modulating activity (1.52-, 1.52- and 1.46-fold, respectively) than
      those of crude polysaccharide from nonfermented ginseng (NG-CP, 1.36-, 1.37- and
      1.32-fold) and G. lucidum mycelium alone (GL-CP, 1.48-, 1.40- and 1.31-fold).
      After FG-GL-CP was further fractionated into two active carbohydrate-rich
      fractions (FG-GL-CP-II and III) on DEAE-Sepharose CL-6B (Cl- form), the most
      active polysaccharide (FG-GL-CP-III-1) was purified as a single peak with a
      molecular weight of 71 kDa. FG-GL-CP-III-1 mainly consists of Ara, Man, Gal, and
      Glc (molar ratio: 0.85:1.00:0.81:0.76) in addition to a small amount of uronic
      acid. Methylation analysis indicates that FG-GL-CP-III-1 is composed mainly of
      terminal/4- or 5-linked Ara(f), terminal/4-linked Man, terminal/3,6-branched Gal,
      and terminal/4-linked Glc. NaIO4 oxidation of FG-GL-CP-III significantly
      decreased its activity (64.0-79.2%). These results suggest that solid-state
      culture of ginseng with G. lucidum may enhance the immunomodulatory activity and
      that neutral polysaccharides containing Ara, Man, Gal, and Glc may be important
      for the activity of fermented ginseng.

PMID- 24456367
TI  - Beneficial effects of Korean traditional diets in hypertensive and type 2
      diabetic patients.
AB  - The prevalence of metabolic syndrome, hypertension, and diabetes has been
      increasing rapidly in Korea. The rate of increase has paralleled the replacement
      of Korean traditional diets (KTD), which emphasize vegetables and fermented
      foods, with western style dietary patterns that are rich in animal foods and
      saturated fat. We aimed to investigate the efficacy of the KTD in controlling
      fasting plasma glucose, blood pressure, and cardiovascular disease risk factors
      in hypertensive and type 2 diabetic (T2D) patients. Forty-one patients (61.8+/
      1.5 years) who were taking medications prescribed for respective diseases were
      recruited from the Chonbuk National University Hospital for participation in a 12
      week, parallel, controlled clinical trial. The control group (n=20) was advised
      to "eat as usual," whereas the experimental KTD diet group (n=21) was fed the KTD
      three times a day for 12 weeks. At the end of the trial, both groups had lower
      body mass index, % body fat, and waist-hip ratio compared to the baseline values
      (P<.05). Compared to the control group, the KTD group had a greater mean change
      (P<.05) from the baseline for glycated hemoglobin (HbA1c) (-0.72% vs. -0.25%) and
      heart rate (-7.1 vs. +1.6). Regular consumption of the KTD for 12 weeks by
      hypertensive and T2D patients resulted in favorable changes in cardiovascular
      risk factors.

PMID- 24456368
TI  - Association between kimchi intake and asthma in Korean adults: the fourth and
      fifth Korea National Health and Nutrition Examination Survey (2007-2011).
AB  - This study was performed to investigate the relationship between dietary factors
      and asthma in a representative population-based sample of 19,659 men and women,
      aged 19-64 years, using data from the fourth and fifth Korean National Health and
      Nutrition Examination Survey (KNHANES), 2007-2011. The presence of asthma was
      based on self-reported physician diagnosis of asthma in the Health Interview
      Surveys. Food intake was estimated by trained interviewers using a 24-h recall
      method. The prevalence of asthma in Korean adults was 2.4%. Adults with asthma
      consumed fewer amounts of kimchi (P=.0444) and fish (P=.0175) but had a higher
      cereal intake than those without asthma (P=.0056). Multiple logistic regression
      analysis after controlling for confounding factors showed a significant inverse
      relationship between kimchi consumption and the prevalence of asthma [odds ratio
      (95% confidence interval) for subjects consuming 1 to <2 servings (40-79.9 g), 2
      to <3 servings (80-119.9 g), and >=3 servings (>=120 g), relative to those
      consuming <1 serving (<40 g): 0.726 (0.534-0.987), 0.506 (0.348-0.736), and 0.678
      (0.502-0.916), respectively; P for trend=0.0131]. These results warrant future
      studies to explore the mechanisms responsible for the association between kimchi
      consumption and asthma.

PMID- 24456369
TI  - Drug design targeting protein-protein interactions (PPIs) using multiple ligand
      simultaneous docking (MLSD) and drug repositioning: discovery of raloxifene and
      bazedoxifene as novel inhibitors of IL-6/GP130 interface.
AB  - The IL-6/GP130/STAT3 pathway is critical for the progression of multiple types of
      cancers. We report here the discovery of raloxifene and bazedoxifene as novel
      inhibitors of IL-6/GP130 protein-protein interactions (PPIs) using multiple
      ligand simultaneous docking (MLSD) and drug repositioning approaches. Multiple
      drug scaffolds were simultaneously docked into hot spots of GP130 D1 domain by
      MLSD to compete with the key interacting residues of IL-6, followed by tethering
      to generate virtual hit compounds. Similarity searches of virtual hits on drug
      databases identified raloxifene and bazedoxifene as potential inhibitors of IL
      6/GP130 interaction. In cancer cell assays both compounds bind to GP130 and
      demonstrated selective inhibition of IL-6 induced STAT3 phosphorylation and were
      significantly more potent than the previously reported natural product inhibitor
      MDL-A. The identified drugs represent a new class of lead compounds with
      piperidine, benzothiophene, and indole scaffolds to inhibit IL-6 induced
      homodimerization of GP130. Besides potential direct usage for clinic trials, the
      two compounds can also serve as lead compounds for optimization to speed the
      development of drugs selectively targeting the IL-6/GP130/STAT3 cancer signaling
      pathway. 

PMID- 24456370
TI  - Reading in Spanish and Italian: effects of age of acquisition in transparent
      orthographies?
AB  - Despite the similar transparency of their orthographies, reading in Italian has
      been found to be affected by frequency but not age of acquisition (AoA) [Barca,
      L., Burani, C., & Arduino, L. S. (2002). Word naming times and psycholinguistic
      norms for Italian nouns. Behaviour Research Methods, Instruments and Computers,
      34, 424-434] while reading in Spanish is affected by AoA but not frequency
      [Cuetos, F., & Barbon, A. (2006). Word naming in Spanish. European Journal of
      Cognitive Psychology, 18, 415-436]. We examined this cross-linguistic difference,
      firstly, through a reanalysis of the Italian and Spanish reading latencies. After
      eliminating several between-experiment differences, we replicated the AoA effect
      in Spanish but not in Italian and the frequency effect in Italian but not in
      Spanish. The cross-linguistic comparison could not equate stimulus imageability;
      therefore, secondly, we compared the Italian reading latencies with new Spanish
      reading latencies for imageability-matched words. We found frequency effects but
      neither an AoA effect nor a language by AoA interaction. We argue that the
      previously reported cross-linguistic difference in the AoA effect resulted from a
      between-study difference in stimulus imageability. More imageable words induced
      more semantic involvement in reading, yielding an AoA effect in Spanish. 

PMID- 24456371
TI  - Diagnosis and management of pediatric brugada syndrome: a survey of pediatric
      electrophysiologists.
AB  - BACKGROUND: Brugada syndrome (BrS) can be difficult to diagnose and treat,
      especially in the young patient. As there is currently no consensus on the
      evaluation and treatment of BrS in the pediatric population, we sought to
      describe the current practice for the diagnosis and treatment of BrS among
      pediatric electrophysiologists. METHODS: A web-based survey was distributed to
      204 physician members (MDs) of The Pediatric and Adult Congenital
      Electrophysiology Society (PACES). Practice characteristics, BrS patient
      attributes, and diagnostic and therapeutic preferences were collected. RESULTS:
      Responses were obtained from 83 pediatric electrophysiologists. The most common
      initial presentation was family history. There is a large variation in testing,
      particularly in the use of electrophysiology (EP) studies, drug challenge
      testing, and genetic testing. Despite limited treatment options, there is only
      consensus in the therapeutic approach to the pediatric patient with symptomatic
      BrS with 97% of physicians recommending an implantable cardioverter defibrillator
      (ICD). In the asymptomatic patient, a wide variation in therapy was seen with
      only 27% of physicians recommending an ICD CONCLUSIONS: Significant practice
      variation exists among pediatric electrophysiologists with deviation from
      accepted diagnostic and therapeutic practices for adult BrS patients. Further
      studies are necessary to establish best practice guidelines for BrS in the
      pediatric EP community.

PMID- 24456372
TI  - Outcomes of biopsies and excisions of dysplastic acral nevi: a study of 187
      lesions.
AB  - BACKGROUND: Despite their frequency in clinical practice, controversy exists
      regarding the significance and management of dysplastic nevi (DN). Although the
      perception of DN as precursors to melanoma is questionable, excisions of biopsy
      proven DN are commonplace in clinical practice. The management of dysplastic
      acral nevi is of interest given the challenge of surgery at acral sites.
      OBJECTIVE: To determine the outcomes of biopsies of clinically atypical acral
      nevi and excisions of histologically dysplastic acral nevi (HDN). MATERIALS AND
      METHODS: Retrospective review of consecutive patients at a private dermatology
      practice who had a biopsy of an atypical acral nevus from December 2004 to July
      2012. RESULTS: One hundred eighty-seven atypical acral nevi were biopsied from
      168 patients (77 (41%) HDN, 108 (58%) common nevi). Based on initial histology,
      30 (39%) HDN were recommended for excision and eight (10%) for clinical
      observation. Twenty-seven of the 77 HDN were excised; 23 (85%) revealed scar
      only, and four (15%) revealed residual DN not involving the margin. CONCLUSION:
      Routine excision of biopsy-proven dysplastic acral nevi may not be necessary.

PMID- 24456373
TI  - Comparison of 2-week versus 4-week dosing intervals of epoetin beta pegol on
      erythropoiesis and iron metabolism in hemodialysis patients.
AB  - Epoetin beta pegol (a continuous erythropoietin receptor activator; CERA) is
      usually administered once in 4 weeks or once monthly. However, the optimal dosing
      interval remains unknown. We, therefore, compared the effect of CERA
      administration between dosing intervals of 2 weeks (TWICE group) and 4 weeks
      (ONCE group) on erythropoiesis and iron metabolism in 20 hemodialysis patients.
      CERA was administered intravenously at weeks 0 and 2 for the TWICE group, and at
      week 0 for the ONCE group. Levels of hemoglobin (Hb), reticulocyte count,
      ferritin, transferrin saturation, content of Hb in reticulocytes and hepcidin-25
      were monitored weekly for 4 weeks. Hemoglobin levels were significantly increased
      at weeks 3 and 4 in the TWICE group, while a gradual decrease after a significant
      increase at week 1 was observed in the ONCE group. Ferritin levels remained
      significantly low from week 1 to week 4 in the TWICE group. On the other hand,
      ferritin levels increased beyond baseline levels at week 4 in the ONCE group.
      Although hepcidin-25 did not significantly increase in the TWICE group,
      significant increases beyond baseline levels at weeks 3 and 4 were found in the
      ONCE group. These results indicate that continuous erythropoiesis was achieved
      with biweekly administration of CERA. Moreover, CERA at a 2-week interval led to
      a sustained suppression of ferritin and hepcidin-25 levels, suggesting a
      favorable influence on iron metabolism. 

PMID- 24456374
TI  - Current pharmacological treatment approaches for alcohol dependence.
AB  - INTRODUCTION: At present, the substances acamprosate, naltrexone and disulfiram
      are available for pharmacotherapy in alcohol dependence, but clinical studies
      found only modest effect sizes of these treatment options. AREAS COVERED: This
      article focuses on current pharmacological treatment approaches for alcohol
      dependence, which have been evaluated in randomized, placebo-controlled trials
      (RCTs). EXPERT OPINION: Besides the opioid system modulator nalmefene, which has
      recently been approved as a medication for the reduction of alcohol consumption,
      several compounds have been investigated in patients with alcohol dependence
      using a randomized, placebo-controlled design. In these studies, the
      antiepileptic drugs topiramate and gabapentin were found to be effective in
      improving several drinking-related outcomes, whereas levetiracetam failed to show
      efficacy in the treatment of alcohol dependence. Clinical studies using (low
      dose) baclofen, a selective GABA-B receptor agonist, produced conflicting
      results, so that results of further trials are needed. Varenicline has also shown
      mixed results in two RCTs, but might possibly be useful in patients with comorbid
      nicotine dependence. The alpha1 adrenergic antagonist prazosin is currently under
      investigation in alcohol dependence with and without comorbid posttraumatic
      stress disorder (PTSD). Finally, first clinical evidence suggests that the 5-HT3
      antagonist ondansetron might possibly be used in future within a pharmacogenetic
      treatment approach in alcohol dependence.

PMID- 24456375
TI  - Emergence of Bluetongue Virus Serotype 1 in French Corsica Island in September
      2013.
AB  - Since 2000, French Corsica Island has been exposed to the emergence of three
      different BT virus (BTV) serotypes: serotype 2 in 2000 and 2001, serotype 4 in
      2003 and serotype 16 in 2004. Between 2005 and August 2013, no outbreaks have
      been reported in the French Island. At the beginning of September 2013, sheep
      located in the south of the island showed clinical signs suggestive of BTV
      infection. Laboratory analyses identified the virus as BTV serotype 1.
      Phylogenetic studies showed that the sequences of this strain are closely related
      to the BTV-1 strain that was circulating in the Mediterranean basin and in
      Sardinia in 2012.

PMID- 24456377
TI  - GRIA2 is a novel diagnostic marker for solitary fibrous tumour identified through
      gene expression profiling.
AB  - AIMS: The NAB2-STAT6 fusion was recently identified as a consistent finding in
      solitary fibrous tumour (SFT), resulting in nuclear expression of the C-terminal
      part of STAT6. Gene expression studies of SFT revealed high expression of the
      GRIA2 gene. The aim of this study was to examine GRIA2 expression in SFTs and
      other soft tissue tumours to evaluate its diagnostic utility. METHODS AND
      RESULTS: Immunohistochemistry was performed on 375 soft tissue tumours. In total,
      84 of 105 (80%) SFTs, including 86% of malignant SFTs and 100% of
      dedifferentiated SFTs, were positive for GRIA2. One SFT known to harbour the NAB2
      STAT6 fusion but that was negative for STAT6 by immunohistochemistry was positive
      for GRIA2. It is of note that 93% of SFTs received in the last 3 years were
      positive for GRIA2, as compared with only 70% of older cases. The only other
      tumours that expressed GRIA2 were 15 of 20 (75%) cases of dermatofibrosarcoma
      protuberans (DFSP), four of nine (44%) myoepitheliomas, one synovial sarcoma (<1%
      of cells), and one schwannoma. CONCLUSIONS: GRIA2 is a useful marker for
      distinguishing SFT from most mimics. Among other CD34-positive tumours, GRIA2 is
      also expressed in DFSP; however, clinical and histological features aid in their
      distinction. GRIA2 shows a limited distribution in other soft tissue tumours.

PMID- 24456376
TI  - The roots of plant defenses: integrative multivariate analyses uncover dynamic
      behaviors of gene and metabolic networks of roots elicited by leaf herbivory.
AB  - High-throughput analyses have frequently been used to characterize herbivory
      induced reconfigurations in plant primary and secondary metabolism in above- and
      below-ground tissues, but the conclusions drawn from these analyses are often
      limited by the univariate methods used to analyze the data. Here we use our
      previously described multivariate time-series data analysis to evaluate leaf
      herbivory-elicited transcriptional and metabolic dynamics in the roots of
      Nicotiana attenuata. We observed large, but transient, systemic responses in the
      roots that contrasted with the pattern of co-linearity observed in the up- and
      downregulation of genes and metabolites across the entire time series in treated
      and systemic leaves. Using this newly developed approach for the analysis of
      whole-plant molecular responses in a time-course multivariate data set, we
      simultaneously analyzed stress responses in leaves and roots in response to the
      elicitation of a leaf. We found that transient systemic responses in roots
      resolved into two principal trends characterized by: (i) an inversion of root
      specific semi-diurnal (12 h) transcript oscillations and (ii) transcriptional
      changes with major amplitude effects that translated into a distinct suite of
      root-specific secondary metabolites (e.g. alkaloids synthesized in the roots of
      N. attenuata). These findings underscore the importance of understanding tissue
      specific stress responses in the correct day-night phase context and provide a
      holistic framework for the important role played by roots in above-ground stress
      responses. 

PMID- 24456378
TI  - Incidence and outcomes of major trauma patients managed in the Australian Capital
      Territory.
AB  - BACKGROUND: To determine the incidence and characteristics of major traumatic
      injury treated in the Australian Capital Territory (ACT) over a 5-year period.
      METHODS: A retrospective analysis of ACT Level 1 Trauma Centre registry data from
      July 2007 to June 2012 was conducted. Inclusion criteria were: major trauma
      (Injury Severity Score (ISS) >15), intensive care unit admission, hospital stay
      >3 days or penetrating injury. RESULTS: There were 931 patients with an ISS >15,
      a 12.5% increase over the 5-year period (P = 0.003). Unadjusted mortality rates
      in the ISS >15 group remained stable at 9.9%. About half of all injuries occurred
      outside the ACT. The largest age group represented was 16-24 years. Road trauma
      was the most prevalent injury mechanism, but its incidence reduced over the 5
      year period (52.2-40.3% [P = 0.005]). There was a 3.1% increase in admissions
      following violence. CONCLUSION: The largest demographic affected by major trauma
      in the ACT and surrounds is young people. Injury prevention should remain focused
      on road trauma but also target violence and high-risk recreation activities.
      Further investigation around the circumstances of major traumatic injury in young
      people is required. Funding and cross-border agreements should be reviewed to
      minimize financial disadvantage to the ACT.

PMID- 24456379
TI  - Increasing issues in Cochlear Implants International.

PMID- 24456380
TI  - Measures of the electrically evoked compound action potential threshold and slope
      in HiRes 90K(TM) users.
AB  - OBJECTIVES: To investigate electrically evoked compound action potentials (eCAPs)
      measured with the neural response imaging (NRI) 'SmartNRI' algorithm. NRI
      thresholds and slopes were examined according to three aspects: (1) site along
      the cochlea, (2) development of responses over time, and (3) influence of
      age/duration of deafness. METHODS: Thirty-four individuals implanted with the
      Advanced Bionics HiRes 90K(TM) device were included. The eCAP recordings were
      made from four electrodes along the array at first fitting and at frequent
      intervals up to at least 2 years. Slope and threshold (tNRI) of the amplitude
      growth function were measured and a range of explanatory variables were tested
      for significant effects on these measures using multi-factorial analysis of
      variance. RESULTS: Electrode position emerged as a significant effect for the
      tNRI measure, with lowest thresholds at the apical end of the array. Mean slope
      was greatest for the most apical electrode, but not significantly. Slope was
      significantly influenced by onset of deafness, with congenital hearing loss
      associated with steeper slopes than acquired hearing loss. There was also a
      highly significant effect of duration of device use, with a gradual increase in
      slope over the 2 years following device activation. DISCUSSION: The observed
      effects of electrode position are consistent with a model in which eCAP threshold
      is governed primarily by an effect of distance between electrode and neural
      interface (which is shorter towards the apex of the cochlea) and in which slope
      is governed primarily by density of surviving neural elements.

PMID- 24456381
TI  - Family caregiver challenges in dementia care in Australia and China: a critical
      perspective.
AB  - BACKGROUND: Both Australia and China have a large proportion of people with
      dementia and the prevalence will triple in Australia and increase five times in
      China by 2050. The majority of people with dementia are reliant on family
      caregivers to provide daily care and to maintain the dignity in both countries.
      As a consequence, caregiver burden has become a major concern because of the
      negative impact on the care recipients' and the caregivers' health. It is
      strongly recommended that cross-national collaboration should be conducted to
      share experiences in fighting dementia. The aim of this study was to compare
      socially and culturally constructed enablers and barriers pertinent to dementia
      caregivers in one capital city in Australia and one capital city in China through
      critical reflection on the caregivers' subjective and objective experiences for
      the improvement of dementia care services in both countries. METHODS: Giddens'
      Structuration Theory was used as a framework to guide a concurrent mixed methods
      design with the qualitative strand as a priority. In the qualitative strand, data
      were collected by focus groups and in-depth interviews while in the quantitative
      strand, data were collected by questionnaire survey. RESULTS: In total 148
      caregivers participated in the project with 57 of them from Australia (26 and 31
      in the qualitative and quantitative strands respectively) and 91 of them from
      China (23 and 68 in the qualitative and quantitative strands respectively).
      Findings from the qualitative and quantitative strands were presented as three
      categories: A higher objective burden in the Chinese cohort versus a higher
      subjective burden in the Australian cohort; Unmet need for caregiver support in
      Australia and China; and Expectations for improving dementia services in
      Australia and for developing dementia services in China. CONCLUSIONS: Dementia
      policy, services and resources need to be grounded on current research evidence
      in an ever-changing society like China. In Australia, dementia services need to
      have more components of preventing or reducing caregivers' subjective burden. As
      subjective burden is mediated by culture, caregiver support mechanisms should
      consider caregivers' needs associated with their cultural values.

PMID- 24456382
TI  - Multiple conformations of a single SNAREpin between two nanodisc membranes reveal
      diverse pre-fusion states.
AB  - SNAREpins must be formed between two membranes to allow vesicle fusion, a
      required process for neurotransmitter release. Although its post-fusion structure
      has been well characterized, pre-fusion conformations have been elusive. We used
      single-molecule FRET and EPR to investigate the SNAREpin assembled between two
      nanodisc membranes. The SNAREpin shows at least three distinct dynamic states,
      which might represent pre-fusion intermediates. Although the N-terminal half
      above the conserved ionic layer maintains a robust helical bundle structure, the
      membrane-proximal C-terminal half shows high FRET, representing a helical bundle
      (45%), low FRET, reflecting a frayed conformation (39%) or mid FRET revealing an
      as-yet unidentified structure (16%). It is generally thought that SNAREpins are
      trapped at a partially zipped conformation in the pre-fusion state, and complete
      SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor)
      assembly happens concomitantly with membrane fusion. However, our results show
      that the complete SNARE complex can be formed without membrane fusion, which
      suggests that the complete SNAREpin formation could precede membrane fusion,
      providing an ideal access to the fusion regulators such as complexins and
      synaptotagmin 1. 

PMID- 24456383
TI  - Role of surface functional groups in ordered mesoporous carbide-derived
      carbon/ionic liquid electrolyte double-layer capacitor interfaces.
AB  - Ordered mesoporous carbide-derived carbon (OM-CDC) with a specific surface area
      as high as 2900 m(2) g(-1) was used as a model system in a supercapacitor setup
      based on an ionic liquid (IL; 1-ethyl-3-methylimidazolium tetrafluoroborate)
      electrolyte. Our study systematically investigates the effect of surface
      functional groups on IL-based carbon supercapacitors. Oxygen and chlorine
      functionalization was achieved by air oxidation and chlorine treatment,
      respectively, to introduce well-defined levels of polarity. The latter was
      analyzed by means of water physisorption isotherms at 298 K, and the
      functionalization level was quantified with X-ray photoelectron spectroscopy.
      While oxygen functionalization leads to a decreased capacitance at higher power
      densities, surface chlorination significantly improves the rate capability. A
      high specific capacitance of up to 203 F g(-1) was observed for a chlorinated OM
      CDC sample with a drastically increased rate capability in a voltage range of +/
      3.4 V. 

PMID- 24456384
TI  - Probiotic treatment for the prevention of antibiotic-associated diarrhoea in
      geriatric patients: a multicentre randomised controlled pilot study.
AB  - OBJECTIVE: The objective of the study was to evaluate effectiveness of probiotic
      supplementation in reducing antibiotic-associated diarrhoea (AAD). METHOD: A
      double-blind randomised controlled trial (registration number: ACTRN
      12609000429257); with primary outcome prevention of AAD and secondary outcome
      reduction in diarrhoea duration, patients were randomised to receive probiotic
      supplementation with Lactobacillus casei, Shirota strain or placebo. RESULTS:
      Eighty-seven people (66-101 years old) were recruited to the study during their
      admission to the Geriatric Evaluation Management wards during August-October
      2009. 41 received the active Yakult (Yakult Australia Pty Ltd, Dandenong South,
      Victoria, Australia) (12.2% diarrhoea) and 46 received placebo (8.7% diarrhoea).
      There was no significant difference in diarrhoea between the groups, Fisher's
      exact test, P = 0.729. The mean diarrhoea duration was 4 and 5 days for those
      administered Yakult and placebo, respectively. CONCLUSION: There was no
      significant difference between groups. However, we noted a low prevalence of AAD
      and this affects the sample size that will be required for any future study
      examining a beneficial effect of probiotic supplementation.

PMID- 24456386
TI  - Guillain-Barre syndrome: subtypes and predictors of outcome from India.
AB  - There is a paucity of large studies evaluating the subtypes of Guillain-Barre
      syndrome (GBS) and their outcome from Southeast Asia. We report
      cliniconeurophysiological subtypes of GBS and their correlation with triggering
      events and 3-month outcome from northern India. Three hundred and twenty eight
      consecutive patients with GBS were clinically evaluated, including their
      triggers, severity, autonomic involvement, cranial nerve palsy, and respiratory
      paralysis. Nerve conduction study (NCS) was repeated at 3 weeks if the initial
      study was normal. They were categorized into acute inflammatory demyelinating
      polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor
      sensory axonal neuropathy (AMSAN), inexcitable motor nerve, and equivocal.
      Clinically, 204 (62.2%) patients had pure motor, 106 (32.3%) motor sensory, 16
      (4.9%) Miller Fisher syndrome, and 2 (0.6%) pure sensory GBS. Based on NCS, 242
      (73.8%) had AIDP, 44 (13.4%) AMAN, 15 (4.6%) AMSAN, 8 (2.4%) inexcitable motor
      nerves, and 27 (8.2%) equivocal GBS. AIDP patients were older, more common in
      summer, had lesser peak disability, and better outcome compared to those with
      AMAN. Eleven (3.4%) patients died and 48 (14.6%) had poor outcome at 3 months.
      The poor outcome was related to severity, dysautonomia, and inexcitable motor
      nerves. AIDP is the commonest variant of GBS in our study and has better outcome
      compared to AMAN. 

PMID- 24456387
TI  - A new flavanone from the aerial parts of Penthorum chinense.
AB  - A new flavanone, 5-methoxy-pinocembrin-7-O-beta-D-glucoside (1), together with
      six known compounds, quercetin-3-O-beta-D-xyloside (2), quercetin-3'-O-alpha-L
      rhamnoside (3), quercetin (4), pinocembrin-7-O-beta-D-glucoside (5), pinocembrin
      (6), gallic acid (7), were isolated and identified from the aerial parts of
      Penthorum chinense. Compounds 2 and 3 were isolated from this plant for the first
      time.

PMID- 24456388
TI  - Improvement of red color development on the surface of kuruma prawn Marsupenaeus
      japonicus under various conditions.
AB  - The degree of red color development on the surface of prawns by cooking is an
      important index for food quality. In this study, we tested several factors that
      are thought to influence the red color development to identify possible
      correlations with various conditions. Live kuruma prawns, Marsupenaeus japonicus,
      (15.4 cm, 25.2 g on average) were used in this study. In case of cooking at 100 
      degrees C for 1 min after 24 h of storage at 0  degrees C, 5  degrees C, and 20 
      degrees C, the red color development rate of prawns stored at 5  degrees C and 20
      degrees C was significantly lower than that of prawns cooked just after killing.
      In case of cooking at 100  degrees C, 80  degrees C, and 60  degrees C after
      storage for 24 h at 0  degrees C, there was no color development at 60  degrees C
      and significantly less color development at 80  degrees C compared to cooking
      just after killing. Preparation using 1% sodium carbonate before cooking at 80 
      degrees C could compensate for the lack of red color development. Short exposure
      of live kuruma prawns to low-oxygen conditions had no influence on the color
      development, but putting the prawns in freshwater for 3 h significantly reduced
      the red color development rate. In conclusion, the storage time has little
      influence on the red color development when the cooking temperature is
      sufficiently high. However, in case a large amount of prawns is cooked followed
      by lowering the cooking temperature and/or prawns are exposed to serious stresses
      before cooking, an alkaline preparation could compensate for the lack of red
      color development. 

PMID- 24456389
TI  - Observing, performing, and understanding actions: revisiting the role of cortical
      motor areas in processing of action words.
AB  - Language content and action/perception have been shown to activate common brain
      areas in previous neuroimaging studies. However, it is unclear whether
      overlapping cortical activation reflects a common neural source or adjacent, but
      distinct, sources. We address this issue by using multivoxel pattern analysis on
      fMRI data. Specifically, participants were instructed to engage in five tasks:
      (1) execute hand actions (AE), (2) observe hand actions (AO), (3) observe
      nonbiological motion (MO), (4) read action verbs, and (5) read nonaction verbs. A
      classifier was trained to distinguish between data collected from neural motor
      areas during (1) AE versus MO and (2) AO versus MO. These two algorithms were
      then used to test for a distinction between data collected during the reading of
      action versus nonaction verbs. The results show that the algorithm trained to
      distinguish between AE and MO distinguishes between word categories using signal
      recorded from the left parietal cortex and pre-SMA, but not from ventrolateral
      premotor cortex. In contrast, the algorithm trained to distinguish between AO and
      MO discriminates between word categories using the activity pattern in the left
      premotor and left parietal cortex. This shows that the sensitivity of premotor
      areas to language content is more similar to the process of observing others
      acting than to acting oneself. Furthermore, those parts of the brain that show
      comparable neural pattern for action execution and action word comprehension are
      high-level integrative motor areas rather than low-level motor areas. 

PMID- 24456391
TI  - Bridging the divide between sensory integration and binding theory: Using a
      binding-like neural synchronization mechanism to model sensory enhancements
      during multisensory interactions.
AB  - Neural information combination problems are ubiquitous in cognitive neuroscience.
      Two important disciplines, although conceptually similar, take radically
      different approaches to these problems. Sensory binding theory is largely
      grounded in synchronization of neurons responding to different aspects of a
      stimulus, resulting in a coherent percept. Sensory integration focuses more on
      the influences of the senses on each other and is largely grounded in the study
      of neurons that respond to more than one sense. It would be desirable to bridge
      these disciplines, so that insights gleaned from either could be harnessed by the
      other. To link these two fields, we used a binding-like oscillatory
      synchronization mechanism to simulate neurons in rattlesnake that are driven by
      one sense but modulated by another. Mutual excitatory coupling produces
      synchronized trains of action potentials with enhanced firing rates. The same
      neural synchronization mechanism models the behavior of a population of cells in
      cat visual cortex that are modulated by auditory activation. The coupling
      strength of the synchronizing neurons is crucial to the outcome; a criterion of
      strong coupling (kept weak enough to avoid seriously distorting action potential
      amplitude) results in intensity-dependent sensory enhancement-the principle of
      inverse effectiveness-a key property of sensory integration.

PMID- 24456390
TI  - Facial expressions and the evolution of the speech rhythm.
AB  - In primates, different vocalizations are produced, at least in part, by making
      different facial expressions. Not surprisingly, humans, apes, and monkeys all
      recognize the correspondence between vocalizations and the facial postures
      associated with them. However, one major dissimilarity between monkey
      vocalizations and human speech is that, in the latter, the acoustic output and
      associated movements of the mouth are both rhythmic (in the 3- to 8-Hz range) and
      tightly correlated, whereas monkey vocalizations have a similar acoustic
      rhythmicity but lack the concommitant rhythmic facial motion. This raises the
      question of how we evolved from a presumptive ancestral acoustic-only vocal
      rhythm to the one that is audiovisual with improved perceptual sensitivity.
      According to one hypothesis, this bisensory speech rhythm evolved through the
      rhythmic facial expressions of ancestral primates. If this hypothesis has any
      validity, we expect that the extant nonhuman primates produce at least some
      facial expressions with a speech-like rhythm in the 3- to 8-Hz frequency range.
      Lip smacking, an affiliative signal observed in many genera of primates,
      satisfies this criterion. We review a series of studies using developmental, x
      ray cineradiographic, EMG, and perceptual approaches with macaque monkeys
      producing lip smacks to further investigate this hypothesis. We then explore its
      putative neural basis and remark on important differences between lip smacking
      and speech production. Overall, the data support the hypothesis that lip smacking
      may have been an ancestral expression that was linked to vocal output to produce
      the original rhythmic audiovisual speech-like utterances in the human lineage. 

PMID- 24456392
TI  - Reactivating memories during sleep by odors: odor specificity and associated
      changes in sleep oscillations.
AB  - Memories are reactivated during sleep. Re-exposure to olfactory cues during sleep
      triggers this reactivation and improves later recall performance. Here, we tested
      if the effects of odor-induced memory reactivations are odor-specific, that is,
      requiring the same odor during learning and subsequent sleep. We also tested
      whether odor-induced memory reactivation affects oscillatory EEG activity during
      sleep, as a putative mechanism underlying memory processing during sleep.
      Participants learned a visuospatial memory task under the presence of an odor.
      During subsequent SWS, the same odor, a different odor, or an odorless vehicle
      was presented. We found that odor re-exposure during sleep significantly improves
      memory only when the same odor was presented again, whereas exposure to a new
      odor or the odorless vehicle had no effect. The memory-enhancing effect of the
      congruent odor was accompanied by significant increases in frontal delta (1.5-4.5
      Hz) and parietal fast spindle (13.0-15.0 Hz) power as well as by an increased
      negative-to-positive slope of the frontal slow oscillation. Our results indicate
      that odor-induced memory reactivations are odor specific and trigger changes in
      slow-wave and spindle power possibly reflecting a bottom-up influence of
      hippocampal memory replay on cortical slow oscillations as well as thalamo
      cortical sleep spindles. 

PMID- 24456394
TI  - Attention biases visual activity in visual short-term memory.
AB  - In the current study, we tested whether representations in visual STM (VSTM) can
      be biased via top-down attentional modulation of visual activity in
      retinotopically specific locations. We manipulated attention using retrospective
      cues presented during the retention interval of a VSTM task. Retrospective cues
      triggered activity in a large-scale network implicated in attentional control and
      led to retinotopically specific modulation of activity in early visual areas V1
      V4. Importantly, shifts of attention during VSTM maintenance were associated with
      changes in functional connectivity between pFC and retinotopic regions within V4.
      Our findings provide new insights into top-down control mechanisms that modulate
      VSTM representations for flexible and goal-directed maintenance of the most
      relevant memoranda.

PMID- 24456393
TI  - The necessity of the medial temporal lobe for statistical learning.
AB  - The sensory input that we experience is highly patterned, and we are experts at
      detecting these regularities. Although the extraction of such regularities, or
      statistical learning (SL), is typically viewed as a cortical process, recent
      studies have implicated the medial temporal lobe (MTL), including the
      hippocampus. These studies have employed fMRI, leaving open the possibility that
      the MTL is involved but not necessary for SL. Here, we examined this issue in a
      case study of LSJ, a patient with complete bilateral hippocampal loss and broader
      MTL damage. In Experiments 1 and 2, LSJ and matched control participants were
      passively exposed to a continuous sequence of shapes, syllables, scenes, or tones
      containing temporal regularities in the co-occurrence of items. In a subsequent
      test phase, the control groups exhibited reliable SL in all conditions,
      successfully discriminating regularities from recombinations of the same items
      into novel foil sequences. LSJ, however, exhibited no SL, failing to discriminate
      regularities from foils. Experiment 3 ruled out more general explanations for
      this failure, such as inattention during exposure or difficulty following test
      instructions, by showing that LSJ could discriminate which individual items had
      been exposed. These findings provide converging support for the importance of the
      MTL in extracting temporal regularities. 

PMID- 24456396
TI  - Effect of microstimulation of the superior colliculus on visual space attention.
AB  - We investigated the effect of microstimulation of the superficial layers of the
      superior colliculus (SC) on the performance of animals in a peripheral detection
      paradigm while maintaining fixation. In a matching-to-sample paradigm, a sample
      stimulus was presented at one location followed by a brief test stimulus at that
      (relevant) location and a distractor at another (irrelevant) location. While
      maintaining fixation, the monkey indicated whether the sample and the test
      stimulus matched, ignoring the distractor. The relevant and irrelevant locations
      were switched from trial to trial. Cells in the superficial layers of SC gave
      enhanced responses when the attended test stimulus was inside the receptive field
      compared with when the (physically identical) distractor was inside the field.
      These effects were found only in an "automatic" attentional cueing paradigm, in
      which a peripheral stimulus explicitly cued the animal as to the relevant
      location in the receptive field. No attentional effects were found with block of
      trials. The transient enhancement to the attended stimulus was observed at the
      onset and not at the offset of the stimulus. Electrical stimulation at the site
      corresponding to the irrelevant distractor location in the SC causes it to gain
      control over attention, causing impaired performance of the task at the relevant
      location. Stimulation at unattended sites without the presence of a distractor
      stimulus causes little or no impairment in performance. The effect of stimulation
      decays with successive stimulations. The animals learn to ignore the stimulation
      unless the parameters of the task are varied. 

PMID- 24456397
TI  - Recognizing an object from the sum of its parts: an intracranial study on alpha
      rhythms.
AB  - Little is known about the relation of alpha rhythms and object recognition. Alpha
      has been generally proposed to be associated with attention and memory and to be
      particularly important for the mediation of long-distance communication between
      neuronal populations. However, how these apply to object recognition is still
      unclear. This study aimed at describing the spatiotemporal dynamics of alpha
      rhythms while recognizing fragmented images of objects presented for the first
      time and presented again 24 hr later. Intracranial electroencephalography was
      performed in six epileptic patients undergoing presurgical evaluation. Time
      frequency analysis revealed a strong alpha activity, mainly of the evoked type,
      propagating from posterior cerebral areas to anterior regions, which was similar
      whether the objects were recognized or not. Phase coherence analysis, however,
      showed clear phase synchronization specific for the moment of recognition. Twenty
      four hr later, frontal regions displayed stronger alpha activity and more
      distributed phase synchronization than when images were presented for the first
      time. In conclusion, alpha amplitude seems to be related to nonspecific
      mechanism. Phase coherence analysis suggests a communicational role of alpha
      activity in object recognition, which may be important for the comparison between
      bottom-up representations and memory templates. 

PMID- 24456395
TI  - Subcortical projections of area V2 in the macaque.
AB  - To investigate the subcortical efferent connections of visual area V2, we
      injected tritiated amino acids under electrophysiological control into 15 V2
      sites in 14 macaques. The injection sites included the fovea representation as
      well as representations ranging from central to far peripheral eccentricities in
      both the upper and lower visual fields. The results indicated that V2 projects
      topographically to different portions of the inferior and lateral pulvinar and to
      the superficial and intermediate layers of the superior colliculus. Within the
      pulvinar, the V2 projections terminated in fields P1, P2, and P4, with the
      strongest projection being in P2. Central visual field injections in V2 labeled
      projection zones in P1 and P2, whereas peripheral field injections labeled P1,
      P2, and P4. No projections were found in P3. Both central and peripheral field
      injections in V2 projected topographically to the superficial and intermediate
      layers of the superior colliculus. Projections from V2 to the pulvinar and the
      superior colliculus constituted cortical-subcortical loops through which circuits
      serving spatial attention are activated. 

PMID- 24456398
TI  - Dissociable neuroanatomical correlates of subsecond and suprasecond time
      perception.
AB  - The ability to estimate durations varies across individuals. Although previous
      studies have reported that individual differences in perceptual skills and
      cognitive capacities are reflected in brain structures, it remains unknown
      whether timing abilities are also reflected in the brain anatomy. Here, we show
      that individual differences in the ability to estimate subsecond and suprasecond
      durations correlate with gray matter (GM) volume in different parts of cortical
      and subcortical areas. Better ability to discriminate subsecond durations was
      associated with a larger GM volume in the bilateral anterior cerebellum, whereas
      better performance in estimating the suprasecond range was associated with a
      smaller GM volume in the inferior parietal lobule. These results indicate that
      regional GM volume is predictive of an individual's timing abilities. These
      morphological results support the notion that subsecond durations are processed
      in the motor system, whereas suprasecond durations are processed in the parietal
      cortex by utilizing the capacity of attention and working memory to keep track of
      time. 

PMID- 24456400
TI  - The Arabidopsis Mediator subunit MED16 regulates iron homeostasis by associating
      with EIN3/EIL1 through subunit MED25.
AB  - Iron is an essential micronutrient for plants and animals, and plants are a major
      source of iron for humans. Therefore, understanding the regulation of iron
      homeostasis in plants is critical. We identified a T-DNA insertion mutant, yellow
      and sensitive to iron-deficiency 1 (yid1), that was hypersensitive to iron
      deficiency, containing a reduced amount of iron. YID1 encodes the Arabidopsis
      Mediator complex subunit MED16. We demonstrated that YID1/MED16 interacted with
      another subunit, MED25. MED25 played an important role in regulation of iron
      homeostasis by interacting with EIN3 and EIL1, two transcription factors in
      ethylene signaling associated with regulation of iron homeostasis. We found that
      the transcriptome in yid1 and med25 mutants was significantly affected by iron
      deficiency. In particular, the transcription levels of FIT, IRT1 and FRO2 were
      reduced in the yid1 and med25 mutants under iron-deficient conditions. The
      finding that YID1/MED16 and MED25 positively regulate iron homeostasis in
      Arabidopsis increases our understanding of the complex transcriptional regulation
      of iron homeostasis in plants. 

PMID- 24456399
TI  - Individual differences in crossmodal brain activity predict arcuate fasciculus
      connectivity in developing readers.
AB  - Crossmodal integration of auditory and visual information, such as phonemes and
      graphemes, is a critical skill for fluent reading. Previous work has demonstrated
      that white matter connectivity along the arcuate fasciculus (AF) is predicted by
      reading skill and that crossmodal processing particularly activates the posterior
      STS (pSTS). However, the relationship between this crossmodal activation and
      white matter integrity has not been previously reported. We investigated the
      interrelationship of crossmodal integration, both in terms of behavioral
      performance and pSTS activity, with AF tract coherence using a rhyme judgment
      task in a group of 47 children with a range of reading abilities. We demonstrate
      that both response accuracy and pSTS activity for crossmodal (auditory-visual)
      rhyme judgments was predictive of fractional anisotropy along the left AF.
      Unimodal (auditory-only or visual-only) pSTS activity was not significantly
      related to AF connectivity. Furthermore, activity in other reading-related ROIs
      did not show the same AV-only AF coherence relationship, and AV pSTS activity was
      not related to connectivity along other language-related tracts. This study is
      the first to directly show that crossmodal brain activity is specifically related
      to connectivity in the AF, supporting its role in phoneme-grapheme integration
      ability. More generally, this study helps to define an interdependent neural
      network for reading-related integration.

PMID- 24456401
TI  - Native ureteropyelostomy: an effective therapy for urinary tract complications
      following kidney transplantation.
AB  - BACKGROUND: Urinary tract complications are relevant sources of morbidity and
      mortality after kidney transplantation. Incidence is reported within 3-14% in
      recent studies. Secondary ureteropyelostomy using the native ureter is a surgical
      option to treat severe urinary tract complications after kidney
      transplantation.The aim of this study was to evaluate the outcome after
      ureteropyelostomy using the native ureter in the management of urinary tract
      complications after kidney transplantation. METHODS: A single centre,
      retrospective clinical review of prospectively collected data of all patients who
      received kidney transplantation or combined kidney-pancreas transplantation
      between January 2001 and June 2009 was performed. All patients who underwent
      surgical therapy for urinary tract complications were identified and followed up
      to evaluate graft function and survival. RESULTS: Six hundred forty-six patients
      received kidney transplantation or combined kidney/pancreas transplantation.
      Twenty-six patients (4%) had to undergo re-operation due to severe urinary tract
      complications after kidney transplantation. Sixteen of the 26 patients (62%)
      received ureteropyelostomy using the ipsilateral native ureter. This
      reconstructive operation was successful in 14 of 16 patients (87.5%). Two
      patients needed to be re-operated for surgical complications. CONCLUSION:
      Ureteropyelostomy using the native ureter to treat ureter-related urinary tract
      complications after kidney transplantation can be performed safely and result in
      good graft and patient survival.

PMID- 24456402
TI  - Monitoring phosphatidic acid formation in intact phosphatidylcholine bilayers
      upon phospholipase D catalysis.
AB  - We have monitored the production of the negatively charged lipid, 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphatidic acid acid (POPA), in supported lipid bilayers
      via the enzymatic hydrolysis of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (PC), a zwitterionic lipid. Experiments were performed with phospholipase D (PLD)
      in a Ca(2+) dependent fashion. The strategy for doing this involved using
      membrane-bound streptavidin as a biomarker for the charge on the membrane. The
      focusing position of streptavidin in electrophoretic-electroosmotic focusing
      (EEF) experiments was monitored via a fluorescent tag on this protein. The
      negative charge increased during these experiments due to the formation of POPA
      lipids. This caused the focusing position of streptavidin to migrate toward the
      negatively charged electrode. With the use of a calibration curve, the amount of
      POPA generated during this assay could be read out from the intact membrane, an
      objective that has been otherwise difficult to achieve because of the lack of
      unique chromophores on PA lipids. On the basis of these results, other enzymatic
      reactions involving the change in membrane charge could also be monitored in a
      similar way. This would include phosphorylation, dephosphorylation, lipid
      biosynthesis, and additional phospholipase reactions. 

PMID- 24456403
TI  - Outcome predictors for problem drinkers treated with combined cognitive
      behavioral therapy and naltrexone.
AB  - BACKGROUND: The opioid antagonist naltrexone, combined with cognitive behavioural
      therapy (CBT), has proven efficacious for patients with alcohol dependence, but
      studies examining how this treatment works in a naturalistic treatment setting
      are lacking. OBJECTIVES: This study examined predictors of the outcome of
      targeted naltrexone and CBT in a real-life outpatient setting. Participants were
      315 patients who attended a treatment program providing CBT combined with the
      targeted use of naltrexone. METHODS: Mixture models for estimating developmental
      trajectories were used to examine change in patients' alcohol consumption and
      symptoms of alcohol craving from treatment entry until the end of the treatment
      (20 weeks) or dropout. Predictors of treatment outcome were examined with
      analyses of multinomial logistic regression. Minimal exclusion criteria were
      applied to enhance the generalizability of the findings. RESULTS: Regular
      drinking pattern, having no history of previous treatments, and high-risk alcohol
      consumption level before the treatment were associated with less change in
      alcohol use during the treatment. The patients with low-risk alcohol consumption
      level before the treatment had the most rapid reduction in alcohol craving.
      Patients who drank more alcohol during the treatment had lower adherence with
      naltrexone. CONCLUSION: Medication non-adherence is a major barrier to
      naltrexone's effectiveness in a real-life treatment setting. Patients with more
      severe alcohol problems may need more intensive treatment for achieving better
      treatment outcome in real-word treatment settings.

PMID- 24456405
TI  - Influence of the chemical structure on odor qualities and odor thresholds in
      homologous series of alka-1,5-dien-3-ones, alk-1-en-3-ones, alka-1,5-dien-3-ols,
      and alk-1-en-3-ols.
AB  - Odor qualities and odor thresholds in air in homologous series of synthesized alk
      1-en-3-ols and alka-1,5-dien-3-ols and their corresponding ketones were evaluated
      by gas chromatography-olfactometry. In the series of the alk-1-en-3-ols and alk-1
      en-3-ones the odor quality changed successively from pungent for the compounds
      with five carbon atoms via metallic, vegetable-like for the six- and seven-carbon
      odorants to mushroom-like for the compounds with eight and nine carbon atoms.
      With further increase in chain length the mushroom-like impression decreased and
      changed to citrus-like, soapy, or herb-like. In both series, two odor threshold
      minima were found for the six-carbon and also for the eight- and nine-carbon
      odorants, respectively. In contrast to this, the odor qualities in the series of
      the (Z)- and (E)-alka-1,5-dien-3-ols and their corresponding ketones did not
      change significantly with geranium-like, metallic odors and an increasing
      mushroom-like odor note with increasing chain length. The lowest thresholds were
      found for the eight- and nine-carbon (Z)-compounds, respectively. 

PMID- 24456406
TI  - Quantification of the 248 nm photolysis products of HCNO (fulminic acid).
AB  - IR diode laser spectroscopy was used to detect the products of HCNO (fulminic
      acid) photolysis at 248 nm. Five product channels are energetically possible at
      this photolysis wavelength: O + HCN, H + (NCO), CN + OH, CO + NH, and HNCO. In
      some experiments, isotopically labeled (18)O2, (15)N(18)O and C2D6 reagents were
      included into the photolysis mixture in order to suppress and/or isotopically
      label possible secondary reactions. HCN, OC(18)O, C(18)O, NCO, DCN, and NH
      molecules were detected upon laser photolysis of HCNO/reagents/buffer gas
      mixtures. Analysis of the yields of product molecules leads to the following
      photolysis quantum yields: phi1a (O + HCN) = 0.39 +/- 0.07, phi1b (H + (NCO)) =
      0.21 +/- 0.04, phi1c (CN + OH) = 0.16 +/- 0.04, phi1d (CN + NH(a(1)Delta)) = 0.19
      +/- 0.03, and phi1e (HNCO) = 0.05 +/- 0.02, respectively. The uncertainties
      include both random errors (1sigma) and consideration of major sources of
      systematic error. In conjunction with the photolysis experiment, the H + HCNO
      reaction was investigated. Experimental data demonstrate that this reaction is
      very slow and does not contribute significantly to the secondary chemistry. 

PMID- 24456407
TI  - Synthesis, spectroscopic, and photophysical characterization and photosensitizing
      activity toward prokaryotic and eukaryotic cells of porphyrin-magainin and 
      buforin conjugates.
AB  - Cationic antimicrobial peptides (CAMPs) and photodynamic therapy (PDT) are
      attractive tools to combat infectious diseases and to stem further development of
      antibiotic resistance. In an attempt to increase the efficiency of bacteria
      inactivation, we conjugated a PDT photosensitizer, cationic or neutral porphyrin,
      to a CAMP, buforin or magainin. The neutral and hydrophobic porphyrin, which is
      not photoactive per se against Gram-negative bacteria, efficiently
      photoinactivated Escherichia coli after conjugation to either buforin or
      magainin. Conjugation to magainin resulted in the considerable strengthening of
      the cationic and hydrophilic porphyrin's interaction with the bacterial cells, as
      shown by the higher bacteria photoinactivation activity retained after washing
      the bacterial suspension. The porphyrin-peptide conjugates also exhibited strong
      interaction capability as well as photoactivity toward eukaryotic cells, namely,
      human fibroblasts. These findings suggest that these CAMPs have the potential to
      carry drugs and other types of cargo inside mammalian cells similar to cell
      penetrating peptides. 

PMID- 24456408
TI  - Does tonal information affect the early stages of visual-word processing in Thai?
AB  - Thai offers a unique opportunity to investigate the role of lexical tone
      processing during visual-word recognition, as tone is explicitly expressed in its
      script. In order to investigate the contribution of tone at the
      orthographic/phonological level during the early stages of word processing in
      Thai, we conducted a masked priming experiment-using both lexical decision and
      word naming tasks. For a given target word (e.g., ????/h?:n2/, room), five
      priming conditions were created: (a) identity (e.g., ????/h?:n2/), (b) same
      initial consonant, but with a different tone marker (e.g., ????/h?:n1/), (c)
      different initial consonant, but with the same tone marker (e.g., ????/s?:n2/),
      (d) orthographic control (different initial consonant, different tone marker;
      e.g., ????/s?:n1/), and (e) same tone homophony, but with a different initial
      consonant and different tone marker (e.g., ????/t(h)?:n2/). Results of the
      critical comparisons revealed that segmental information (i.e., consonantal
      information) appears to be more important than tone information (i.e., tone
      marker) in the early stages of visual-word processing in alphabetic, tonal
      languages like Thai. Thus, these findings may help constrain models of visual
      word recognition and reading in tonal languages. 

PMID- 24456409
TI  - Expertise facilitates the transfer of anticipation skill across domains.
AB  - It is unclear whether perceptual-motor skill transfer is based upon similarity
      between the learning and transfer domains per identical elements theory, or
      facilitated by an understanding of underlying principles in accordance with
      general principle theory. Here, the predictions of identical elements theory,
      general principle theory, and aspects of a recently proposed model for the
      transfer of perceptual-motor skill with respect to expertise in the learning and
      transfer domains are examined. The capabilities of expert karate athletes, near
      expert karate athletes, and novices to anticipate and respond to stimulus skills
      derived from taekwondo and Australian football were investigated in ecologically
      valid contexts using an in situ temporal occlusion paradigm and complex whole
      body perceptual-motor skills. Results indicated that the karate experts and near
      experts are as capable of using visual information to anticipate and guide motor
      skill responses as domain experts and near-experts in the taekwondo transfer
      domain, but only karate experts could perform like domain experts in the
      Australian football transfer domain. Findings suggest that transfer of
      anticipation skill is based upon expertise and an understanding of principles but
      may be supplemented by similarities that exist between the stimulus and response
      elements of the learning and transfer domains. 

PMID- 24456410
TI  - Self-assembled biodegradable protein-polymer vesicle as a tumor-targeted
      nanocarrier.
AB  - Self-assembled nanostructures based on amphiphilic protein-polymer conjugates
      have shown great advantages in the field of nanomedicine such as inherent
      biocompatibility with biosystems because of their excellent performance. Herein,
      a novel biodegradable protein-polymer conjugate was prepared by covalently
      linking the tailor-made hydrophobic maleimide-functionalized poly(epsilon
      caprolactone) (PCL) to hydrophilic bovine serum albumin (BSA) via the maleimide
      sulfhydryl coupling reaction. This protein-based conjugate with a biodegradable
      polyester was reported for the first time, and the obtained biohybrid displayed
      well-defined structure, excellent biocompatibility and low cytotoxicity, and self
      assembly behaviors similar to those of the traditional amphiphilic small
      molecules and block copolymers. The amphiphilic BSA-PCL conjugate can self
      assemble into a nanosized vesicle with a negative surface charge. Furthermore,
      the self-assembled vesicle based on the BSA-PCL conjugate was functionalized via
      linking targeting ligand cetuximab to its surface to enhance cell uptake, and the
      doxorubicin (DOX)-encapsulated cetuximab-functionalized vesicle exhibited
      enhanced antitumor activity compared with that of free DOX in vitro. These
      results indicate that the biodegradable protein-polymer conjugate based on BSA
      and PCL had great potential as a drug delivery vehicle for cancer therapy. 

PMID- 24456411
TI  - Preterm labor: current tocolytic options for the treatment of preterm labor.
AB  - While tocolytic therapy may not be indicated in all cases of spontaneous preterm
      labor (SPTL), the evidence that they are superior to placebo is robust. The
      perfect tocolytic that is 100% efficacious and 100% safe does not exist and
      efforts should continue to develop and introduce safer and more effective agents.
      A reduction in the rate of neonatal mortality and morbidity using tocolysis has
      not been shown but no tocolytic study has been powered by numbers sufficient to
      demonstrate such an effect. Tocolytics can delay delivery long enough to
      administer a course of antepartum glucocorticoids and arrange in utero transfer
      to a center with neonatal intensive care facilities, both of which reduce
      neonatal mortality and morbidity. Few tocolytics (beta2-agonists and atosiban)
      are licensed for use as tocolytics and only one was developed specifically to
      treat preterm labor (atosiban). Accordingly, most tocolytics have multi-organ
      adverse effects. Currently, based on the evidence of safety and efficacy,
      atosiban should be the first-choice tocolytic for the treatment of SPTL to
      prevent or delay preterm birth.

PMID- 24456412
TI  - Treatment of postmenopausal osteoporosis with odanacatib.
AB  - INTRODUCTION: The market of anti-osteoporosis drugs has been declining in recent
      years, possibly in part due to the publicity around adverse events observed with
      bisphosphonates. Also, the proportion of patients with clinical fracture who
      receive adequate treatment remains low. So there are still unmet needs in this
      field. Odanacatib is a cathepsin K inhibitor currently being developed for the
      treatment of postmenopausal osteoporosis that could be an advance in this
      context. AREAS COVERED: Odanacatib is a bone resorption inhibitor, but it
      preserves some degree of bone formation, which differentiates this new family of
      drugs from existing therapies. Odanacatib increases bone mineral density at the
      spine and hip, improves estimated bone strength using finite element analysis at
      the spine and hip as well as at the distal tibia and radius. The safety profile
      has been satisfactory so far. A robust antifracture efficacy has been announced
      when the Phase III pivotal trial was terminated after interim analysis, but we do
      not yet have access to the complete results. EXPERT OPINION: Odanacatib may have
      an important role in future guidelines if it provides a substantial advantage
      compared to the effective and inexpensive current generic drugs, in terms of
      antifracture efficacy or safety.

PMID- 24456413
TI  - Long-term effects of BRAF inhibitors in melanoma treatment: friend or foe?
AB  - The clinical development of selective BRAF inhibitors for metastatic BRAF V600
      mutant melanoma patients has been a major breakthrough in targeted therapeutics.
      Objective response rates of approximately 50% have been observed in the Phase III
      studies of the BRAF inhibitors vemurafenib and dabrafenib. The side effects can
      be relatively common, including proliferative skin toxicities. The latter range
      from hyperkeratosis and keratoacanthomas (KAs) to squamous cell carcinomas (SCCs)
      and new primary melanomas. In addition, case reports on the emergence of
      gastric/colonic polyps and RAS mutant malignancies have been described during
      BRAF inhibitor therapy. These events have been attributed to paradoxical
      activation of the MAPK pathway in BRAF wild-type cells exposed to selective BRAF
      inhibitors in addition to increased RAS activity. Combined BRAF and MEK
      inhibition appears to improve clinical outcomes and reduce cutaneous
      proliferation events as fewer KAs and SCCs have been observed with combination
      therapy. Next-generation pan-RAF inhibitors ('paradox breakers') and ERK
      inhibitors may further enhance clinical activity in metastatic BRAF-mutant
      melanoma patients and mitigate this paradoxical oncogenesis. Further
      investigation into the potential long-term effects of selective BRAF inhibitors
      is warranted as expanded use of these agents is expected in patients with BRAF
      mutant melanoma and other malignancies. 

PMID- 24456414
TI  - Middle East respiratory syndrome coronavirus antibody reactors among camels in
      Dubai, United Arab Emirates, in 2005.
AB  - We tested, using a low starting dilution, sequential serum samples from dromedary
      camels, sheep and horses collected in Dubai from February/April to October of
      2005 and from dromedary camels for export/import testing between Canada and USA
      in 2000-2001. Using a standard Middle East respiratory syndrome coronavirus (MERS
      CoV) neutralization test, serial sera from three sheep and three horses were all
      negative while sera from 9 of 11 dromedary camels from Dubai were positive for
      antibodies supported by similar results in a MERS-CoV recombinant partial spike
      protein antibody ELISA. The two negative Dubai camels were both dromedary calves
      and remained negative over the 5 months studied. The six dromedary samples from
      USA and Canada were negative in both tests. These results support the recent
      findings that infection with MERS-CoV or a closely related virus is not a new
      occurrence in camels in the Middle East. Therefore, interactions of MERS-CoV at
      the human-animal interface may have been ongoing for several, perhaps many, years
      and by inference, a widespread pandemic may be less likely unless significant
      evolution of the virus allow accelerated infection and spread potential in the
      human population. 

PMID- 24456415
TI  - Intraductal papillary neoplasms and mucinous cystic neoplasms of the
      hepatobiliary system: demographic differences between Asian and Western
      populations, and comparison with pancreatic counterparts.
AB  - AIMS: To improve the characterization of intraductal papillary neoplasm of the
      bile duct (IPNB) and mucinous cystic neoplasm of the liver (MCN-L). METHODS AND
      RESULTS: A retrospective review of pathology archives (1999-2011) in our three
      institutions identified cases of IPNB (n = 138) and MCN-L (n = 54). The IPNB/MCN
      L ratio was 5.7:1 at Samsung Medical Centre in Seoul, which was significantly
      higher than those at the University of Washington Medical Center in Seattle
      (1:3.0) and King's College Hospital in London (1:6.3). This difference was mainly
      attributable to the considerably larger number of patients with IPNB in Seoul (n
      = 131) than in Seattle and London (n = 7). Western patients with IPNB were all
      non-Asian in ancestry. IPNB differed from pancreatic intraductal papillary
      neoplasm in its higher histological grade, more advanced stage of an associated
      invasive cancer, and worse prognosis. In contrast, MCN-L showed significantly
      lower histological grade than its pancreatic counterpart (P = 0.022). Unlike in
      pancreatic mucinous cystic neoplasm, malignant transformation was very rare in
      MCN-L (10% versus 2%). CONCLUSIONS: This study demonstrated demographic
      differences in IPNB and MCN-L among regions. IPNB and MCN-L differ from their
      pancreatic counterparts in the risk of malignant transformation and patients'
      prognosis.

PMID- 24456416
TI  - The novel alleles HLA-B*44:101 and HLA-B*57:48 of Caucasian origin are
      characterized by amino acid substitutions in the alpha 2 domain.
AB  - HLA-B*44:101 and HLA-B*57:48 are characterized by amino acid substitutions in the
      alpha 2 domain. 

PMID- 24456417
TI  - Connecting the person with dementia and family: a feasibility study of a
      telepresence robot.
AB  - BACKGROUND: Maintenance of communication is important for people with dementia
      living in long-term care. The purpose of this study was to assess the feasibility
      of using "Giraff", a telepresence robot to enhance engagement between family and
      a person with dementia living in long-term care. METHODS: A mixed-methods
      approach involving semi-structured interviews, call records and video
      observational data was used. Five people with dementia and their family member
      participated in a discussion via the Giraff robot for a minimum of six times over
      a six-week period. A feasibility framework was used to assess feasibility and
      included video analysis of emotional response and engagement. RESULTS: Twenty-six
      calls with an average duration of 23 mins took place. Residents showed a general
      state of positive emotions across the calls with a high level of engagement and a
      minimal level of negative emotions. Participants enjoyed the experience and
      families reported that the Giraff robot offered the opportunity to reduce social
      isolation. A number of software and hardware challenges were encountered.
      CONCLUSIONS: Participants perceived this novel approach to engage families and
      people with dementia as a feasible option. Participants were observed and also
      reported to enjoy the experience. The technical challenges identified have been
      improved in a newer version of the robot. Future research should include a
      feasibility trial of longer duration, with a larger sample and a cost analysis.

PMID- 24456418
TI  - Beyond project-focused consultation to investigator-focused consultation: the
      CCTST Integration Committee model.

PMID- 24456419
TI  - Serum prolidase enzyme activity and oxidative stress levels in patients with
      acute hemorrhagic stroke.
AB  - BACKGROUND: It has been indicated that oxidative damage contributes to secondary
      brain injury in both ischemic and hemorrhagic stroke patients. Collagen is a
      major component of the extracellular matrix, and prolidase plays a role in
      collagen synthesis. The aim of this study was to evaluate the serum prolidase
      activity, nitric oxide (NO) levels, total antioxidant capacity (TAC) and total
      oxidant status (TOS) in patients with acute hemorrhagic stroke. METHODS: Twenty
      five patients with acute hemorrhagic stroke and 25 controls were enrolled. Serum
      prolidase activity, catalase activity, NO levels, TAC and TOS were measured
      spectrophotometrically. Oxidative stress index (OSI) was calculated. RESULTS:
      Serum TAC levels and catalase activity were significantly lower in acute
      hemorrhagic stroke patients than controls (both, p < 0.001), while NO levels, TOS
      levels, OSI values and prolidase activity were significantly higher (all, p <
      0.01). When patients with acute hemorrhagic stroke were divided according to
      gender, no differences were observed between females and males in respect to
      serum prolidase enzyme activity, NO levels, TAC levels, TOS levels and OSI values
      (all, p > 0.05). CONCLUSIONS: Findings from the study suggest an association
      between increased oxidative stress levels, decreased antioxidant levels and
      increased prolidase enzyme activity in patients with acute hemorrhagic stroke
      compared with controls. More studies are needed to elucidate mechanistic pathways
      on oxidative stress in patients with acute hemorrhagic stroke.

PMID- 24456420
TI  - Parathyroid hormone-related peptide plasma concentrations in patients on
      hemodialysis.
AB  - BACKGROUND: Uremic patients develop hyperplasia of the parathyroid glands due to
      disturbances in the mineral metabolism. The hyperplastic parathyroids are
      associated with significant expression of parathyroid hormone (PTH)-related
      peptide (PTHrP). PTHrP has been shown to have an autocrine/paracrine function in
      the parathyroids, but it is still uncertain if PTHrP is a secretory product of
      the gland and thereby possess endocrine actions. In cells of severe adenomatous
      secondary hyperparathyroidism PTHrP and PTH have been found to be co-localized in
      the same secretory granules. PTH and PTHrP act through the same receptor, the
      PTH1R, and it has been shown experimentally that PTHrP enhances the PTH secretory
      response to hypocalcemia, indicating a link between the two hormones. METHODS:
      Together with a number of parameters involved in mineral homeostasis plasma PTHrP
      was measured before hemodialysis in 90 patients and in 15 healthy subjects.
      Plasma PTH was determined in order to examine the possible relationship between
      the two peptides. RESULTS: In hemodialysis patients mean plasma PTHrP, 4.2 +/-
      2.1, was significantly lower than that of healthy subjects, 8.3 +/- 1.1 pmol/L, p
      < 0.0001. No relationship was found between plasma PTHrP and PTH in hemodialysis
      patients. Gender, PTX, specific treatments and diagnoses had no impact on PTHrP
      concentrations. CONCLUSION: Thus PTHrP is measurable in hemodialysis patients,
      but its secretion might not be part of a regulated mineral homeostatic process
      and may not derive from the uremic hyperplastic parathyroid glands.

PMID- 24456421
TI  - Metabolic syndrome and diabetes are associated with low serum amylase in a
      Chinese asymptomatic population.
AB  - OBJECTIVE: Previous studies have shown that lower serum amylase levels are
      associated with chronic pancreatitis. However, recently, lower serum amylase
      levels have been associated with metabolic syndrome (MS) and diabetes. The
      objective of the present study was to investigate the relationship between
      metabolic syndrome and diabetes and serum amylase levels in Chinese asymptomatic
      individuals living in Hangzhou, China. METHODS: Serum amylase, triglyceride (TG),
      total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density
      lipoprotein cholesterol (LDL-c), gamma-glutamyltransferase (gamma-GT), high
      sensitivity C reactive protein (hsCRP) and fasting plasma glucose (FPG) levels
      were measured in 3,728 patients from Hangzhou in China. Study participants were
      divided into four groups, Q1-Q4, according to serum amylase levels. Odds ratios
      (OR) of Q1-Q4 were calculated using multivariate logistic regression. RESULTS:
      Significant differences were found in sex, age, body mass index (BMI), systolic
      blood pressure, diastolic blood pressure, gamma-GT, TG, HDL-C and FPG levels, as
      well as the prevalence of metabolic syndrome and diabetes among these four
      groups. Across Q1 to Q4, the prevalence of metabolic syndrome and diabetes
      decreased from 28.5-15.2% and 10.1-3.6%, respectively. Multiple logistic
      regression models following adjustment for age, gender, BMI, and gamma-GT showed
      that the prevalence of metabolic syndrome (OR: 1.284; 95% CI: 0.909-1.813) and
      diabetes (OR: 2.081; 95% CI: 1.230-3.523) in the Q1 was significantly higher
      compared to the Q4. CONCLUSIONS: Low serum amylase levels are significantly
      associated with an increased prevalence of metabolic syndrome and diabetes in a
      Chinese asymptomatic population.

PMID- 24456422
TI  - Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic
      manifestations.
AB  - OBJECTIVE: Over the last decades Lipocalin-type prostaglandin D synthase (L
      PGDS), Osteoprotegerin (OPG), Osteopontin (OPN) and Pregnancy associated plasma
      protein A (PAPP-A) have been reported to be associated with coronary artery
      disease, and L-PGDS has been proposed as a potential new diagnostic tool in the
      setting of stable coronary artery disease. We set out to investigate if
      measurement of concentrations of these biomarkers could be used to differentiate
      between four groups of individuals with different atherosclerotic manifestations.
      METHODS: A total of 120 individuals from four equal gender- and age-matched
      groups were studied: (i) no previous cardiovascular disease (CVD) and no coronary
      calcifications [CAC-negative group], (ii) no previous CVD but evidence of severe
      coronary calcifications [CAC-positive group], (iii) acute coronary syndrome [ACS
      group], and (iv) clinical stable patients with CVD, who were referred for
      cardiovascular surgery [CVD-group]. Concentrations of L-PGDS, OPG, OPN and PAPP-A
      were analyzed and compared between the four groups. RESULTS: We did not find any
      significant differences in L-PGDS concentrations between the four groups (p =
      0.32). OPG concentrations differed significantly (p = 0.003), with the highest
      concentration observed in ACS patients. Considering OPN (p = 0.12) and PAPP-A (p
      = 0.53) their concentrations between groups did not differ significantly.
      CONCLUSION: The main message from this study is the observation that L-PGDS based
      on a single blood test appears to be less valuable than previously proposed in
      identification of patients with coronary artery disease. However, ACS patients
      have higher OPG concentrations than patients with different manifestations of
      stable atherosclerosis. Neither OPN nor PAPP-A concentrations differed between
      groups.

PMID- 24456423
TI  - Relationship of endothelial cell selective adhesion molecule to markers of
      oxidative stress in type 2 diabetes.
AB  - BACKGROUND: Endothelial dysfunction is an important contributor to micro and
      macrovascular complications of type 2 diabetes (T2D) and is reflected by
      increased systemic oxidative stress. Endothelial cell selective adhesion molecule
      (ESAM) influences endothelial function. We aimed to assess, for the first time to
      our knowledge, the relationship of soluble ESAM to markers of systemic oxidative
      stress. MATERIALS AND METHODS: ESAM, malondialdehyde (MDA) level and catalase
      activity were determined in 54 T2D patients and 43 controls. RESULTS: T2D
      patients had significantly higher ESAM when compared to controls (16.07 +/- 5.77
      MUg/L versus 8.57 +/- 5.28 MUg/L, p < 0.0001), they also had higher MDA level
      (3.88 +/- 1.50 MUmol/L vs. 1.58 +/- 0.72 MUmol/L, p < 0.0001) and lower catalase
      activity (3.07 (2.63-3.44) U/mg vs. 8.72 (4.55-10.46) U/mg, p < 0.0001). In T2D
      patients ESAM was inversely related to catalase activity (r = -0.27, p = 0.04),
      relationship to MDA level was direct but not significant (r = 0.16, p = 0.24).
      MDA concentration correlated inversely to catalase activity (r = -0.28, p =
      0.04). In multiple regression catalase activity remained significantly correlated
      to ESAM (p = 0.02) and MDA level was significantly related to glycated hemoglobin
      (p = 0.01); there was trend towards a positive correlation of MDA level to ESAM
      (p = 0.08). When patients were divided according to oxidative stress, those with
      increased oxidative stress (defined as MDA concentration > 2.98 MUmol/L and
      catalase activity < 3.38 U/mg) had higher ESAM than the rest of the patients
      (17.99 +/- 5.02 MUg/L vs. 14.29 +/- 5.94 MUg/L p = 0.01). CONCLUSION: ESAM is
      higher in T2D than in controls and parallels oxidative stress: ESAM is inversely
      related to catalase activity and higher ESAM is found in T2D patients with
      increased oxidative stress.

PMID- 24456425
TI  - Should catheter ablation be the preferred approach for treatment of atrial
      fibrillation related symptomatic sinus node dysfunction?

PMID- 24456424
TI  - MCM3 could be a better marker than Ki-67 for evaluation of dysplastic oral
      lesions: an immunohistochemical study.
AB  - BACKGROUND: The aim of this study was to identify the expression of MCM3, Ki-67
      and p27 in normal mucosa, leucoplakia and oral squamous cell carcinoma (OSCC) and
      determine whether altered expression could serve as a prognostic marker of a
      malignant progression of dysplastic lesions. METHODS: The samples were collected
      from 37 patients with oral leucoplakia (13 with mild dysplasia - MLD, 12 with
      moderate dysplasia - MD and 12 with severe dysplasia - SD). Eleven samples of
      mouth floor mucocele (M) and 50 floor mouth and tongue samples OSCC of untreated
      patients were included in this study. Immunohistochemical expression of MCM3, Ki
      67 and p27 of all the groups was analysed. Kruskal-Wallis and Dunn's test were
      used to determine differences among groups, and a Pearson's correlation test was
      used to evaluate the correlation between the proteins. RESULTS: Ki-67 expression
      was higher in OSCC than M (P < 0.001) and MLD (P < 0.01) groups, and there was a
      lower expression in M compared with MD and SD (P < 0.05). Regarding p27, its
      expression was lower in OSCC compared with M, MD and SD. MCM3 expression was
      lower in M compared with SD and OSCC (P < 0.001), and MLD showed a lower
      expression when compared SD (P < 0.01) and OSCC (P < 0.001). Moreover, a better
      correlation was observed between the proteins MCM3 and p27 than between Ki-67 and
      p27 proteins when all lesions were examined together. CONCLUSIONS: This study
      showed that MCM3 could be a better marker than Ki-67 for evaluation of dysplastic
      oral lesions.

PMID- 24456426
TI  - Health-related quality of life in Guillain-Barre syndrome patients: a systematic
      review.
AB  - Guillain-Barre syndrome (GBS) encompasses a broad spectrum of health-related
      quality of life (HRQL) determinants, including mobility, fatigue, pain, and
      depression. We systematically reviewed the literature on functional outcome
      domains in which GBS patients experience limitations in the short and long terms
      and evaluated determinants of HRQL in GBS patients. MEDLINE and EMBASE were
      systematically searched by two independent reviewers for articles covering HRQL
      data of GBS patients. Of 730 abstracts screened, 17 articles covering data of 14
      studies matched the selection criteria. The included articles showed that many
      GBS patients experienced physical limitations, even years after the acute phase
      of the disease, while results were inconsistent for perceived levels of pain,
      fatigue, and general mental well-being. Only three papers covered HRQL
      assessments at more than one time point, generally showing large improvements in
      HRQL in the first year after GBS onset, but not thereafter. We appraised the
      methodological quality of included studies using a 13-item checklist; none of the
      articles fulfilled all items and only seven articles presented data on
      correlations between HRQL and determinants. In conclusion, the majority of
      studies on HRQL in GBS patients are cross-sectional and of low methodological
      quality. This paper provides guidance for much needed high-quality studies on
      patterns of patient-perceived recovery after GBS onset. 

PMID- 24456427
TI  - Microbial production of 1alpha-hydroxyvitamin D3 from vitamin D3.
AB  - The microbial transformation of vitamin D3 (1) by the fungi Candida maltosa R42
      and Botrytis allii NRRL 2502 was investigated. Incubation of compound 1 with C.
      maltosa R42 and B. allii NRRL 2502 produced the same three more polar metabolites
      in small yields. The main metabolite was identified as 1alpha-hydroxyvitamin D3
      (2). This biotransformation has utility as a possible tool for the production of
      1alpha-hydroxyvitamin D3 from the readily available vitamin D3 for patients with
      compromised kidney function. 

PMID- 24456428
TI  - Effect of citrate ions on the softening of root crops prepared with freeze-thaw
      impregnation of macerating enzymes.
AB  - Freeze-thaw impregnation is a technique used for the rapid impregnation of
      substances into foodstuffs. Freeze-thaw impregnation with macerating enzymes has
      been applied to soften foodstuffs, while retaining their original shapes and
      flavors. In this study, we found that co-impregnation with citrate ions and
      macerating enzymes significantly facilitated the softening of root crops. When
      burdock roots were processed by the impregnating solution at pH 4.0-5.0, co
      impregnated burdock roots exhibited 1/6-1/3 firmness values compared with burdock
      roots impregnated with only enzymes. The impregnation with citrate ions alone at
      pH 4.0 to 5.0 did not soften burdock roots. The firmness of burdock roots was
      positively correlated with the amount of water-insoluble calcium in the samples.
      The results suggested that the degradation of pectins by pectinolytic activities
      could promote contact with citrate to bridging-calcium ions interacting with the
      pectin chains. Therefore, the softening by the synergistic effect of citrate ions
      and macerating enzymes was related to the amount of pectins contained in root
      crops. That is, the synergistic effect was significant with burdock roots and
      carrots (from which 50% of polysaccharides are pectins) unlike with lotus
      rhizomes and bamboo shoots (from which 30% and 10% of polysaccharides are
      pectins, respectively). PRACTICAL APPLICATION: Freeze-thaw impregnation with
      macerating enzymes and citrate ions can be applied for the production of care
      foods which can be eaten without chewing. The softened products induce the
      pleasure of eating for consumers because their original shapes and flavors are
      retained.

PMID- 24456429
TI  - Severe fetal and neonatal hyperthyroidism years after surgical treatment of
      maternal Graves' disease.
AB  - BACKGROUND: Fetal/neonatal hyperthyroidism is a well-known complication of
      maternal Graves' disease with high concentrations of TSH-receptor antibodies
      (TRAb). Few data are available on the management of fetal hyperthyroidism in
      surgically treated Graves' disease. METHODS: Clinical, ultrasound and biochemical
      data are reported in a fetus/neonate whose mother underwent a thyroidectomy > 10
      years before and whose sibling was thin and hyperthyroid at birth. RESULTS:
      Maternal TRAb were persistently > 40 U/l; unequivocal signs of fetal
      hyperthyroidism were identified at 29 weeks gestational age (GA). The fetus was
      treated through maternal antithyroid drug (ATD) administration; the dose was
      reduced gradually once fetal tachycardia and valve dysfunction disappeared and
      normal T4 was confirmed by fetal blood sampling. Maternal euthyroidism was
      maintained. The neonate showed normal growth for GA and T4 concentration at birth
      but severe hyperthyroidism relapsed from day 13 until day 58. TSH remained
      strongly suppressed throughout the pre- and postnatal course. CONCLUSIONS:
      Prenatal ATD in a taper-off regime allowed normal T4 and growth in a hyperthyroid
      fetus from a thyroidectomised Graves' mother. Fetal TSH cannot be used to adjust
      the ATD dose. Prenatal ATD appears to postpone the onset but does not affect the
      severity or duration of the neonatal hyperthyroid flare.

PMID- 24456430
TI  - Abnormal glucose tolerance later in life in women affected by glucose intolerance
      during pregnancy.
AB  - Gestational diabetes mellitus (GDM) is a condition of abnormal maternal glucose
      tolerance that occurs, or is detected, for the first time during pregnancy. The
      new diagnostic strategies recommend a 75 g, 2-h glucose tolerance test for all
      women not already known to be diabetic, in the early 3rd trimester of pregnancy.
      GDM is diagnosed when one or more values is equal to or exceeds the thresholds
      suggested (i.e. fasting >= 5.1 mmol/l, 1-h >= 10.0 mmol/l and 2-h >= 8.5 mmol/l).
      This criteria will determine a significant increase of the prevalence of GDM,
      primarily because only one abnormal value (OAV), not two, is sufficient to make
      the diagnosis. We also suppose that the new cases of gestational diabetes
      diagnosed with the new criteria will have an increased risk for subsequent
      abnormal glucose tolerance later in life, as it was largely confirmed in the past
      for the patients with two or more abnormal values. 

PMID- 24456431
TI  - A critical analysis of low molecular weight heparin use during pregnancy in a
      tertiary referral centre.
AB  - The aim of this study was to analyse low molecular weight heparin (LMWH) use
      during pregnancy in terms of patient evaluation, treatment indication and social
      and financial costs. This was a retrospective analysis of patients using LMWH in
      their pregnancies. A total of 147 women were included in the study. The most
      common indications were thrombophilia (55/147, 37.4%); recurrent pregnancy loss
      (RPL); (47/147, 32.0%) and previous single pregnancy loss (18/147, 12.2%). In the
      RPL group, 53.1% of patients were not evaluated with standard tests; 31.9% of
      women were incompletely evaluated and 15% were properly evaluated. Out of 104
      women screened for thrombophilia, 32 (32/104, 30.8%) were tested during
      pregnancy. Despite published guidelines and increasing scientific evidence
      against their use in some indications, LMWHs are prescribed widely during
      pregnancy for a variety of indications. Public and healthcare providers'
      education to change this attitude should be implemented. 

PMID- 24456432
TI  - Changing trends in diabetes mellitus in pregnancy.
AB  - The purpose of this study was to identify any changing trends in the incidence
      and caesarean section (CS) rate of pre-gestational diabetes mellitus (DM) and
      gestational diabetes mellitus (GDM) over a 10- year period, between 1999 and
      2008. Although the incidence of pre-gestational DM has not significantly changed
      over the course of the last 10 years, there is an obvious rising trend in the
      incidence of GDM. Despite an increase in the overall CS rate during this time
      period, a parallel increase in the CS rate has not been observed among women
      whose pregnancies are complicated either by gestational or by pre-gestational
      diabetes (PGD). 

PMID- 24456433
TI  - Spontaneous neonatal pneumomediastinum: radiological or clinical diagnosis?
AB  - Spontaneous neonatal pneumomediastinum (PNM) is associated with the aspiration of
      blood or meconium and birth-related trauma and it seems to be more frequent in
      post-term newborns. It is generally asymptomatic, but it is occasionally
      accompanied by mild tachypnoea. Only rarely, it requires oxygen therapy or
      develops into pneumothorax. To evaluate the relationship between the radiological
      and clinical diagnosis in this uncommon problem, from January 2005 to August
      2009, 35 newborns with spontaneous PNM were enrolled in the study. Treatment
      protocol provides for execution of a chest X-ray, clinical check, SatO(2) and
      heart rate monitoring. Clinical diagnosis was accomplished particularly early,
      within the first 24 h of life. Paraphonic and distant tones discovered by cardio
      auscultatory exam disappeared within the following 72 h. A total of 28 newborns
      were asymptomatic (80%); seven were symptomatic (20%); five had transient
      tachypnoea of the newborn; two developed an RDS, with Silverman score >= 3 and
      required O(2) therapy. It is necessary to affirm the importance of early
      diagnosis of this condition, carrying out careful monitoring of newborns at risk,
      to begin timely therapeutic treatments, as oxygen-therapy and to heighten
      alertness for complications, such as pneumothorax.

PMID- 24456434
TI  - Investigation on the suitability of the International Association of Diabetes and
      Pregnancy Study Group diagnostic criteria for gestational diabetes mellitus in
      China.
AB  - The aim of this study was to compare pregnancy outcomes of Chinese women
      diagnosed with gestational hyperglycaemia by the well-established American
      Diabetes Association (ADA) criteria, with those women meeting the newer criteria
      established by International Association of Diabetes and Pregnancy Study Groups
      (IADPSG). The study subjects consisted of 6,201 pregnant Chinese women with a
      singleton pregnancy who had received prenatal care and delivered between December
      2008 and December 2011. Women who were screened positive with 1 h glucose load of
      >= 7.8 mmol/l underwent a diagnostic 3 h oral glucose tolerance test. Gestational
      hyperglycaemia was diagnosed using the ADA criteria and re-diagnosed according to
      the IADPSG criteria. The correlation between the incidences of adverse pregnant
      outcomes with gestational hyperglycaemia was analysed. In total, 570 patients
      (9.19% of 6,201) met the ADA criteria and 676 (10.90% of 6,201) met the IADPSG
      criteria. The 518 patients who met both standards showed a reduced caesarean
      section rate, as compared with 158 patients who only met the IADPSG standard and
      received no intervention (71.2% vs 79.7%, p < 0.05). The IADPSG-only group also
      had a higher rate of macrosomia and pre-eclampsia than the control group. The
      IADPSG criteria identified a group of women previously classified as normal
      according to the ADA criteria, but revealing poor pregnancy outcomes and
      requiring management. Therefore, we conclude that the IADPSG criteria are more
      suitable for the diagnosis of gestational hyperglycaemia in China. 

PMID- 24456435
TI  - Alteration of endometrial receptivity in rats with ovarian hyperstimulation
      syndrome.
AB  - It is unclear if the higher pregnancy rate in patients who experience ovarian
      hyperstimulation syndrome (OHSS) indicates that OHSS is favourable for embryo
      implantation, or if patients should be maintained in a hyperstimulation state in
      order to increase the success rate of embryo transplantation. We developed an
      animal model to determine the endometrial receptivity in rats with OHSS.
      Endometrial mRNA levels of ER, PR, HOXA10 and LIF were determined by semi
      quantitative PCR and ER, PR, HOXA10, LIF and integrin alpha(v) beta(3) protein
      levels were determined by Western blotting. Development of pinopodes in the
      hyperstimulation group was slightly delayed, while in the regular stimulation
      group, development was significantly inhibited. mRNA transcription in the regular
      stimulation group was lower, while transcription in the hyperstimulation group
      was not different from controls. Protein expressions were lowest in the regular
      stimulation. We conclude that OHSS is associated with favourable endometrial
      receptivity, similar to that seen in a normal cycle, and receptivity that is
      increased relative to that seen with a routine stimulation protocol.

PMID- 24456436
TI  - Association between shortened cervical length at 34-36 weeks' gestation and term
      labour in Asian women.
AB  - Cervical length was measured at 34-36 weeks' gestation by transvaginal
      ultrasound. The purpose of measurement of cervical length before term was to
      reveal the association with the onset of term labour. This was a retrospective
      study of 362 women who were delivered at term at Mizmedi hospital, between August
      2006 and November 2011. There was significant linear correlation between cervical
      length and the scan-to-labour interval in women with labour before 41 weeks. The
      measurement of cervical length at 34-36 weeks' gestation might be helpful in
      predicting the onset of term labour before 41 weeks. 

PMID- 24456437
TI  - Chromosomal and structural anomalies in fetuses with open neural tube defects.
AB  - The aim of this study is to evaluate the frequency and types of associated
      anomalies with the results of ultrasonographic and postmortem examination and
      identify the necessity of prenatal karyotyping among fetuses with open neural
      tube defects (NTD). Fetuses diagnosed with NTDs between 2008 and 2012 were
      retrospectively analysed. A total of 167 fetuses that were prenatally karyotyped,
      terminated and examined at postmortem were evaluated. Associated anomalies were
      detected and classified by detailed ultrasonography and autopsy findings. In
      total, 57 fetuses (34.1%) had associated anomalies. Prenatal ultrasonography
      detected 73.1% of additional anomalies compared with autopsy. Three fetuses had
      chromosomal abnormalities with multiple additional anomalies. A complete
      anatomical survey and genetic evaluation is needed for the fetuses with NTDs. We
      found lower chromosomal abnormality rates but due to some factors specific to
      NTDs, ultrasonography may not be predictive as to whether the fetus is isolated
      or not. We still therefore also offer chromosome analysis in isolated cases. 

PMID- 24456438
TI  - A randomized clinical trial evaluating prophylactic single-dose vs prolonged
      course of antibiotics for caesarean section in a high HIV-prevalence setting.
AB  - The evidence that perioperative antibiotics for caesarean delivery are effective
      in reducing infective morbidity is unequivocal. In developing countries,
      especially those with high HIV-prevalence, clinicians have increasingly become
      anxious about the efficacy of perioperative antibiotics, hence the adoption of
      treatment regimens, as described in this study. We set out to investigate if
      these fears have a basis by conducting a randomised clinical trial. The setting
      was two tertiary units in a developing country with a significant HIV-prevalence.
      The outcome measures assessed were: pyrexia, wound infection, admission with
      puerperal sepsis, laparotomy for pelvic abscess and duration of hospital stay.
      There was no statistically significant difference between the two arms of the
      study with regard to the above outcomes. Our conclusion is that the two
      antibiotic regimens are equivalent in preventing infection, therefore there is no
      justification for subjecting patients to week-long antibiotics and the
      unnecessary increase in nurse workload. 

PMID- 24456439
TI  - Trends of vulvar cancer.
AB  - Vulvar cancer is an uncommon malignancy of the female genital tract in developing
      countries, accounting for 3% of gynaecological cancers. Here, cervical cancer is
      an everyday problem; ovarian cancer is the second commonest gynaecological
      cancer; endometrial is less common and vulvar cancer is rare. It is advanced at
      admission, though is a visible cancer. Records of women who had
      histopathologically proven vulvar cancer over 24 years were analysed for
      epidemiological status and preventive possibilities. During the analysis period,
      9,419 total cancer cases were diagnosed; 4,726 (50.17%) were in women. A total of
      39.52% (1,868 of 4,726) were gynaecological; 18 cases were vulvar (0.38% of the
      4,726 women with cancer) and 0.96% of the 1,868 gynaecological cancer cases.
      Decreasing trends were 2.25% between 1984 and 1988, down to 0.33% between 2004
      and 2008. Leading presenting complaints were: dyspareunia, 88.88% (16 of 18
      patients); pruritus 13; ulcers 14; vulvar swelling 12 and urinary problems 13.
      Dystrophy was present in 8 of 18 cases. Overall, four had stage I, one stage II,
      three stage III and four stage IV disease at admission; all at labia majora or
      minora, some too advanced to know origin. Four women with metastasis in the
      lungs, liver and bones could only be given palliation. While vulvar cancer is
      uncommon, advanced disease at admission is a concern. Awareness is essential.
      Research is needed as to why cervical cancer is common and vulvar uncommon, as
      HPV plays a major aetiological role, so that cervical cancer can be prevented,
      with early diagnosis, management of vulvar cancer should also be available. 

PMID- 24456440
TI  - The outcomes of surgical repairs of vesicovaginal fistula in 16 patients.
AB  - We retrospectively analysed 16 patients who underwent surgical repair for
      vesicovaginal fistula (VVF) in our department from 1995 to 2012. A total of 14
      patients (88%) were cured after the primary repair and two patients were cured by
      reoperation. We compared the characteristics of the patients whose VVF occurred
      early and late after surgery. In univariate analysis, the estimated area of the
      fistula was significantly greater in the late-onset group (p = 0.011). There was
      a tendency for the maximum diameter of the fistula to be larger (p = 0.08) and a
      surgical energy device was used more frequently during surgery (p = 0.12) in the
      late-onset group than in the early-onset group. In conclusion, the outcomes of
      surgical VVF repair were acceptable. The characteristics of VVF that developed
      late postoperatively were different from those that developed early
      postoperatively. 

PMID- 24456441
TI  - Use of ultrasound in emergency gynaecology.
AB  - Ultrasound scan (USS) is an important tool for assessing and diagnosing early
      pregnancy and gynaecological emergencies. Providing an ultrasound scanning
      service at all hours would enable and ease prompt diagnosis and appropriate
      management. It would also help hospitals in reducing costs secondary to
      unnecessary admissions due to lack of ultrasound out of hours. We have conducted
      a retrospective observational study that looked into the out of hours admissions
      to a busy early pregnancy unit in a general district hospital, over a 3-month
      period. Our results highlight the important role and possible benefits of using
      ultrasound out of hours and prove it is a cost-effective approach. However,
      providing ultrasound scanning out of hours is affected by limitations of staff
      and resources at each unit. This could be avoided by following a
      multidisciplinary approach in acute services and providing more training for
      medical staff in ultrasound scanning. 

PMID- 24456442
TI  - Impact of ethnicity on urodynamic outcomes.
AB  - The aim of this study was to assess the impact of ethnicity on urodynamic
      outcomes. The urodynamic studies (UDS) of 100 women were analysed; 41 were of
      white Caucasian origin, 35 of Asian origin and 24 of African origin. The presence
      of detrusor overactivity (DOA) in the three ethnic groups was compared and the
      nature of DOA in terms of cystometric capacity, volume of strong desire, maximum
      flow rate (Qmax), volume at which DOA occurred, mean amplitude of contraction and
      number of contractions, were compared. Asian (p < 0.003) and African (p < 0.008)
      women were more likely to have a diagnosis of DOA compared with white Caucasian
      women. There was no difference in UDS outcomes when comparing Asian and African
      Women. The ethnicity did not appear to impact significantly on the nature of the
      DOA. Women of Asian and African origin attending for UDS presented with DOA more
      commonly than those of white Caucasian origin. 

PMID- 24456443
TI  - The prediction of para-aortic lymph node metastasis in endometrioid
      adenocarcinoma of endometrium.
AB  - The aim of this study was to assess factors associated with para-aortic lymph
      node metastasis in endometrioid adenocarcinoma. The data of 157 patients with
      endometrioid adenocancer, who underwent staging surgery, was reviewed
      retrospectively. A total of 23 patients (14.6%) had pelvic and 19 patients
      (12.1%) had para-aortic lymph node metastasis; 21% (4/19) of the patients with
      para-aortic lymph node involvement did not have pelvic lymph node metastasis.
      Para-aortic lymph node involvement was significantly more common in the presence
      of LVSI and pelvic lymph node metastasis, and pelvic lymph node metastasis was
      the only independent risk factor for para-aortic lymph node involvement. The
      sensitivity and NPV of positive pelvic lymph node in the prediction of para
      aortic lymph node metastasis were found to be 78.9% and 97%, respectively. The
      corresponding rates for obturator and/or external iliac lymph node were 63.1% and
      95%, respectively. In conclusion, although pelvic lymph node metastasis is the
      only independent risk factor for para-aortic lymph node involvement, negative
      pelvic lymph node is not enough to omit para-aortic lymph node dissection. On the
      other hand, intraoperative frozen section examination of obturator and/or
      external iliac lymph node to omit para-aortic lymphadenectomy might be a good
      option for the patients who have high medical risks for surgery. 

PMID- 24456444
TI  - Knowledge of and attitude towards human papillomavirus infection and vaccines
      among nurses at a tertiary hospital in South Africa.
AB  - The purpose of this cross-sectional study was to determine factors contributing
      to recommending vaccination to patients, using a self-administered anonymous
      questionnaire given to 345 nurses working at a tertiary hospital in South Africa.
      The average age of the participants was 37.2 years. About three-quarters (73.3%)
      of the nurses were aware of HPV and among them, 38.3% knew that HPV is the most
      common sexually transmitted virus. Nurses had poor knowledge regarding HPV
      infection and the HPV vaccine. The majority (90.9%) of the nurses intended to
      recommend the vaccine to their patients. The nurses who mentioned that
      adolescents and young adults would accept HPV vaccination were more likely to
      recommend HPV vaccination to their patients (OR = 57.78, p = 0.031). Nurses had a
      low level of knowledge regarding HPV infection and vaccines but they were willing
      to recommend the vaccines to their patients. Nurses need to be educated before
      implementing HPV vaccinations nationwide. 

PMID- 24456445
TI  - Oral pregnancy tumour: an update.

PMID- 24456446
TI  - Prenatal diagnosis of pericentric inversion homozygosity for chromosome 9.

PMID- 24456447
TI  - Successful pregnancy in a patient with pulmonary hypertension associated with
      mixed collagen vascular disease.

PMID- 24456448
TI  - Prenatal diagnosis and molecular cytogenetic characterisation of a de novo 18p
      deletion.

PMID- 24456449
TI  - Conservative management of a spontaneous retroperitoneal haematoma following
      caesarean section secondary to an arteriovenous malformation: a rare case.

PMID- 24456450
TI  - Three different pregnancy conditions in a patient with Mullerian anomaly.

PMID- 24456451
TI  - Intrauterine fetal death associated with maternal ketoacidosis as a first
      presentation of diabetes in an African woman.

PMID- 24456452
TI  - Uterine rupture following termination of pregnancy in a scarred uterus.
AB  - We present a series of two cases complicated by uterine rupture following
      termination of pregnancy (TOP) in the 1st and 2nd trimesters using misoprostol in
      women with caesarean section scar. Current literature and practise have also been
      reviewed on ruptured uterus in women with caesarean section scar undergoing TOP
      using misoprostol; the diagnosis of adherent placenta in the 1st and 2nd
      trimesters in women with previous caesarean uterine scar; and likely implications
      of a ruptured uterus. 

PMID- 24456453
TI  - Unusual complication of 1st-trimester surgical abortion in patient with a septate
      uterus: intrauterine fallopian tube herniation.

PMID- 24456454
TI  - A rare case of a bipartite placenta with a transamniotic vascular connection.

PMID- 24456455
TI  - Postpartum pyomyoma: a rare complication of leiomyoma.

PMID- 24456456
TI  - Metastatic small-cell carcinoma of the cervix during pregnancy.

PMID- 24456457
TI  - Cervical schistosomiasis.

PMID- 24456458
TI  - Unusual metastasis of uterine leiomyosarcoma to the adrenal gland with
      intravenous extension to the heart.

PMID- 24456459
TI  - Urethral leiomyoma: a rare presentation.

PMID- 24456460
TI  - Prolapsing vaginal Mullerian cyst with cervical elongation mimicking cystocele.

PMID- 24456461
TI  - Endometrioid adenocarcinoma arising from adenomyosis after black cohosh with St
      John's wort.

PMID- 24456462
TI  - General frost growth mechanism on solid substrates with different stiffness.
AB  - Preventing or delaying frost formation on surfaces is of significant importance
      in many aspects of our daily life. Despite many efforts and improvements recently
      achieved in the design of new icephobic materials and substrates, not all
      proposed solutions are universally applicable and frost formation still remains a
      problem in need of further flexible solutions. In this respect, we propose to
      take benefit from the tunable viscoelastic properties of soft polymer gel
      substrates, since they are known to strongly influence the dropwise condensation
      process of water, and to investigate condensation frosting on them. Using polymer
      gels with different stiffness and a hard substrate as a reference, we demonstrate
      their ability to delay frost formation compared to recent results reported in the
      literature on other solid substrates and in particular on superhydrophobic
      surfaces. By investigating the frost front propagation we singled out a general
      behavior of its dynamic evolution consisting of two processes presenting two
      different time scales. This general growth appears to be independent of
      experimental conditions as well as substrate stiffness. 

PMID- 24456463
TI  - Major repeat components covering one-third of the ginseng (Panax ginseng C.A.
      Meyer) genome and evidence for allotetraploidy.
AB  - Ginseng (Panax ginseng) is a famous medicinal herb, but the composition and
      structure of its genome are largely unknown. Here we characterized the major
      repeat components and inspected their distribution in the ginseng genome. By
      analyzing three repeat-rich bacterial artificial chromosome (BAC) sequences from
      ginseng, we identified complex insertion patterns of 34 long terminal repeat
      retrotransposons (LTR-RTs) and 11 LTR-RT derivatives accounting for more than 80%
      of the BAC sequences. The LTR-RTs were classified into three Ty3/gypsy (PgDel,
      PgTat and PgAthila) and two Ty1/Copia (PgTork and PgOryco) families. Mapping of
      30-Gbp Illumina whole-genome shotgun reads to the BAC sequences revealed that
      these five LTR-RT families occupy at least 34% of the ginseng genome. The
      Ty3/Gypsy families were predominant, comprising 74 and 33% of the BAC sequences
      and the genome, respectively. In particular, the PgDel family accounted for 29%
      of the genome and presumably played major roles in enlargement of the size of the
      ginseng genome. Fluorescence in situ hybridization (FISH) revealed that the
      PgDel1 elements are distributed throughout the chromosomes along dispersed
      heterochromatic regions except for ribosomal DNA blocks. The intensity of the
      PgDel2 FISH signals was biased toward 24 out of 48 chromosomes. Unique gene
      probes showed two pairs of signals with different locations, one pair in
      subtelomeric regions on PgDel2-rich chromosomes and the other in interstitial
      regions on PgDel2-poor chromosomes, demonstrating allotetraploidy in ginseng. Our
      findings promote understanding of the evolution of the ginseng genome and of that
      of related species in the Araliaceae. 

PMID- 24456464
TI  - Ready to put metadata on the post-2015 development agenda? Linking data
      publications to responsible innovation and science diplomacy.
AB  - Metadata refer to descriptions about data or as some put it, "data about data."
      Metadata capture what happens on the backstage of science, on the trajectory from
      study conception, design, funding, implementation, and analysis to reporting.
      Definitions of metadata vary, but they can include the context information
      surrounding the practice of science, or data generated as one uses a technology,
      including transactional information about the user. As the pursuit of knowledge
      broadens in the 21(st) century from traditional "science of whats" (data) to
      include "science of hows" (metadata), we analyze the ways in which metadata serve
      as a catalyst for responsible and open innovation, and by extension, science
      diplomacy. In 2015, the United Nations Millennium Development Goals (MDGs) will
      formally come to an end. Therefore, we propose that metadata, as an ingredient of
      responsible innovation, can help achieve the Sustainable Development Goals (SDGs)
      on the post-2015 agenda. Such responsible innovation, as a collective learning
      process, has become a key component, for example, of the European Union's 80
      billion Euro Horizon 2020 R&D Program from 2014-2020. Looking ahead, OMICS: A
      Journal of Integrative Biology, is launching an initiative for a multi-omics
      metadata checklist that is flexible yet comprehensive, and will enable more
      complete utilization of single and multi-omics data sets through data
      harmonization and greater visibility and accessibility. The generation of
      metadata that shed light on how omics research is carried out, by whom and under
      what circumstances, will create an "intervention space" for integration of
      science with its socio-technical context. This will go a long way to addressing
      responsible innovation for a fairer and more transparent society. If we believe
      in science, then such reflexive qualities and commitments attained by
      availability of omics metadata are preconditions for a robust and socially
      attuned science, which can then remain broadly respected, independent, and
      responsibly innovative. "In Sierra Leone, we have not too much electricity. The
      lights will come on once in a week, and the rest of the month, dark[ness]. So I
      made my own battery to power light in people's houses." Kelvin Doe (Global
      Minimum, 2012) MIT Visiting Young Innovator Cambridge, USA, and Sierra Leone "An
      important function of the (Global) R&D Observatory will be to provide support and
      training to build capacity in the collection and analysis of R&D flows, and how
      to link them to the product pipeline." World Health Organization (2013) Draft
      Working Paper on a Global Health R&D Observatory.

PMID- 24456466
TI  - Metadata checklist for the integrated personal OMICS study: proteomics and
      metabolomics experiments.

PMID- 24456465
TI  - Toward more transparent and reproducible omics studies through a common metadata
      checklist and data publications.
AB  - Biological processes are fundamentally driven by complex interactions between
      biomolecules. Integrated high-throughput omics studies enable multifaceted views
      of cells, organisms, or their communities. With the advent of new post-genomics
      technologies, omics studies are becoming increasingly prevalent; yet the full
      impact of these studies can only be realized through data harmonization, sharing,
      meta-analysis, and integrated research. These essential steps require consistent
      generation, capture, and distribution of metadata. To ensure transparency,
      facilitate data harmonization, and maximize reproducibility and usability of life
      sciences studies, we propose a simple common omics metadata checklist. The
      proposed checklist is built on the rich ontologies and standards already in use
      by the life sciences community. The checklist will serve as a common denominator
      to guide experimental design, capture important parameters, and be used as a
      standard format for stand-alone data publications. The omics metadata checklist
      and data publications will create efficient linkages between omics data and
      knowledge-based life sciences innovation and, importantly, allow for appropriate
      attribution to data generators and infrastructure science builders in the post
      genomics era. We ask that the life sciences community test the proposed omics
      metadata checklist and data publications and provide feedback for their use and
      improvement.

PMID- 24456467
TI  - Simultaneous targeting of IL-1 and IL-18 is required for protection against
      inflammatory and septic shock.
AB  - RATIONALE: Sepsis is one of the leading causes of death around the world. The
      failure of clinical trials to treat sepsis demonstrates that the molecular
      mechanisms are multiple and are still insufficiently understood. OBJECTIVES: To
      clarify the long disputed hierarchical contribution of several central
      inflammatory mediators (IL-1beta, IL-18, caspase [CASP] 7, CASP1, and CASP11) in
      septic shock and to explore their therapeutic potential. METHODS: LPS- and tumor
      necrosis factor (TNF)-induced lethal shock, and cecal ligation and puncture (CLP)
      were performed in genetically or pharmacologically targeted mice. Body
      temperature and survival were monitored closely, and plasma was analyzed for
      several markers of cellular disintegration and inflammation. MEASUREMENTS AND
      MAIN RESULTS: Interestingly, deficiency of both IL-1beta and IL-18 additively
      prevented LPS-induced mortality. The detrimental role of IL-1beta and IL-18 was
      confirmed in mice subjected to a lethal dose of TNF, or to a lethal CLP
      procedure. Although their upstream activator, CASP1, and its amplifier, CASP11,
      are considered potential therapeutic targets because of their crucial involvement
      in endotoxin-induced toxicity, CASP11- or CASP1/11-deficient mice were not, or
      hardly, protected against a lethal TNF or CLP challenge. In line with our results
      obtained in genetically deficient mice, only the combined neutralization of IL-1
      and IL-18, using the IL-1 receptor antagonist anakinra and anti-IL-18 antibodies,
      conferred complete protection against endotoxin-induced lethality. CONCLUSIONS:
      Our data point toward the therapeutic potential of neutralizing IL-1 and IL-18
      simultaneously in sepsis, rather than inhibiting the upstream inflammatory
      caspases.

PMID- 24456468
TI  - Gas cleaning and hydrogen sulfide removal for COREX coal gas by sorption enhanced
      catalytic oxidation over recyclable activated carbon desulfurizer.
AB  - This paper proposes a novel self-developed JTS-01 desulfurizer and JZC-80
      alkaline adsorbent for H2S removal and gas cleaning of the COREX coal gas in
      small-scale and commercial desulfurizing devices. JTS-01 desulfurizer was loaded
      with metal oxide (i.e., ferric oxides) catalysts on the surface of activated
      carbons (AC), and the catalyst capacity was improved dramatically by means of
      ultrasonically assisted impregnation. Consequently, the sulfur saturation
      capacity and sulfur capacity breakthrough increased by 30.3% and 27.9%,
      respectively. The whole desulfurizing process combined selective adsorption with
      catalytic oxidation. Moreover, JZC-80 adsorbent can effectively remove impurities
      such as HCl, HF, HCN, and ash in the COREX coal gas, stabilizing the system
      pressure drop. The JTS-01 desulfurizer and JZC-80 adsorbent have been
      successfully applied for the COREX coal gas cleaning in the commercial plant at
      Baosteel, Shanghai. The sulfur capacity of JTS-01 desulfurizer can reach more
      than 50% in industrial applications. Compared with the conventional dry
      desulfurization process, the modified AC desulfurizers have more merit,
      especially in terms of the JTS-01 desulfurizer with higher sulfur capacity and
      low pressure drop. Thus, this sorption enhanced catalytic desulfurization has
      promising prospects for H2S removal and other gas cleaning. 

PMID- 24456472
TI  - Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53
      inhibitor in clinical development.
AB  - We recently reported the discovery of AM-8553 (1), a potent and selective
      piperidinone inhibitor of the MDM2-p53 interaction. Continued research
      investigation of the N-alkyl substituent of this series, focused in particular on
      a previously underutilized interaction in a shallow cleft on the MDM2 surface,
      led to the discovery of a one-carbon tethered sulfone which gave rise to
      substantial improvements in biochemical and cellular potency. Further
      investigation produced AMG 232 (2), which is currently being evaluated in human
      clinical trials for the treatment of cancer. Compound 2 is an extremely potent
      MDM2 inhibitor (SPR KD = 0.045 nM, SJSA-1 EdU IC50 = 9.1 nM), with remarkable
      pharmacokinetic properties and in vivo antitumor activity in the SJSA-1
      osteosarcoma xenograft model (ED50 = 9.1 mg/kg). 

PMID- 24456473
TI  - Non-suicidal self-harm behavior within the previous year among 10th-grade
      adolescents in Istanbul and related variables.
AB  - BACKGROUND: Non-suicidal self-harm behavior (SHB), which is a pervasive and
      dangerous problem, is frequent among adolescents and it is important to evaluate
      the associated psychological and social factors to better understand its nature
      and to plan treatment programs. AIMS: Aim of the present study is to determine
      the prevalence of SHB and the associated variables such as substance use,
      psychological, behavioral and social factors among 10th-grade students in
      Istanbul/Turkey. METHODS: Cross-sectional online self-report survey conducted in
      45 schools from the 15 districts in Istanbul/Turkey. A representative sample of
      4957 10th-grade students was studied between October 2012 and December 2012.
      RESULTS: SHB within the previous year were reported by 14.4% of the students (n =
      713). Lifetime suicidal thoughts or behavior, tobacco, alcohol and/or drug use,
      symptoms of depression, anxiety and impulsive, delinquent and aggressive
      behaviors were also associated with SHB in Turkish 10th-grade students.
      CONCLUSIONS: The findings of the present study may be relevant in prevention and
      management of SHB as well as important problems among students, such as substance
      use, impulsive, delinquent, aggressive and suicidal behavior.

PMID- 24456474
TI  - Solution-processed PEDOT:PSS/graphene composites as the electrocatalyst for
      oxygen reduction reaction.
AB  - Composites of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)
      and reduced graphene oxide (rGO) have been prepared by solution mixing and
      applied as electrocatalysts for oxygen reduction reaction (ORR) after treatment
      with concentrated H2SO4. The blending of rGO induces the conformational change of
      PEDOT chains from benzoid to quionoid structure and charge transfer from rGO to
      PEDOT. H2SO4 post-treatment can remove part of insulating PSS from the surface of
      the PEDOT:PSS/rGO composite film, resulting in a significant conductivity
      enhancement of the composite. This synergistic effect makes the H2SO4-treated
      PEDOT:PSS/rGO composite a promising catalyst for ORR. It exhibits enhanced
      electrocatalytic activity, better tolerance to a methanol crossover effect and CO
      poisoning, and longer durability than those of the platinum/carbon catalyst. 

PMID- 24456475
TI  - ROS1 expression and translocations in non-small-cell lung cancer:
      clinicopathological analysis of 1478 cases.
AB  - AIMS: Molecular characterization of non-small-cell lung cancer (NSCLC) has
      revealed multiple druggable mutations for targeted therapies. Recently,
      chromosomal rearrangements involving c-ros oncogene 1, receptor tyrosine kinase
      (ROS1) were identified, and patients seem to benefit from crizotinib treatment.
      The aim of this study was to identify the clinicopathological characteristics of
      NSCLC with ROS1 expression and translocation. METHODS AND RESULTS: We screened
      1478 NSCLCs with a ROS1-specific antibody, and tested positive cases with FISH.
      All positive cases were analysed for associated clinicopathological
      characteristics, including survival and molecular tumour composition. Sixty-eight
      cases (4.6%) showed ROS1 immunoreactivity, and ROS1 translocations were confirmed
      in nine cases (0.6%). ROS1 expression was predominantly found in female
      adenocarcinoma patients, in patients with low T stages, and in association with
      TTF1 and napsin expression, and certain histomorphological adenocarcinoma
      patterns (lepidic, acinar, and solid). ROS1 translocations occurred in
      conjunction with other driver mutations (EGFR, KRAS, and BRAF). ROS1 expression
      was found to be a stage-independent predictor of favourable survival.
      CONCLUSIONS: ROS1 translocations are rare events in resected NSCLCs from
      Caucasian patients. Immunohistochemical screening for ROS1 expression and
      clinicopathological parameters, including female sex, early tumour stages,
      adenocarcinomas with TTF1 and/or napsin expression, and a distinct
      histomorphological growth pattern, strongly facilitate case enrichment.
      Molecularly driven multistep concepts might not be optimal for case selection.

PMID- 24456476
TI  - A comparison of problem-based and traditional education on nursing students'
      locus of control and problem-solving skills.
AB  - PURPOSE: The purpose of this study is to compare the locus of control and problem
      solving skills of nursing students studying with the problem-based learning
      method with those of nursing students studying with the traditional method.
      METHODS: This is a descriptive and comparative study. For data collection, the
      Problem-Solving Skills Inventory and the Locus of Control Scale were used. The
      study sample included 680 nursing students. CONCLUSIONS: It was determined that
      the problem-based learning method was more effective in the development of
      problem-solving skills and internal locus of control than was the traditional
      method.

PMID- 24456477
TI  - Comparison of adenoid cystic carcinomas arising from the parotid gland vs. the
      submandibular gland: focus on systemic metastasis and tumor-associated blood
      vessels.
AB  - BACKGROUND: Although several studies reported that distant metastasis occurs more
      frequently in the tumors of submandibular gland (SMG) than parotid gland (PG),
      why SMG tumors preferentially metastasize to distant organs is not fully
      understood. We aimed to identify the differential tumor microenvironment for
      distant metastasis and possible underlying mechanisms. METHODS: We retrieved 27
      cases of 1-4-cm-sized adenoid cystic carcinomas (ACCs) arising from the PG (n =
      12) and SMG (n = 15). c-KIT, VEGF-R2, and CD31 staining were quantified by image
      based analysis to define the positive expression or tumor-associated vessel areas
      in two representative sections per case. In addition, angiogenesis-related
      genomic expression profiling was carried out to explore the underlying mechanism,
      which was confirmed by RT-PCR and immunohistochemistry. RESULTS: Earlier systemic
      dissemination within 2 years was detected exclusively in SMG ACCs (5/15). The
      area of tumor-associated blood vessels was larger in SMG ACCs than PG ACCs, and
      ACCs showing distant metastasis had greater blood vessel area than those without
      metastasis. Interestingly, normal SMG had more blood vessels per area than PG.
      Among angiogenesis-related signals, the level of IL-6 was significantly lower in
      SMG ACCs than PG ACCs. Moreover, IL-6 expression decreased significantly in SMG
      ACCs compared with that in normal SMG, whereas it was up-regulated in PG ACCs.
      CONCLUSION: ACCs in the SMG microenvironment have more abundant tumor-associated
      blood vessels than PG ACCs, which may explain the higher risk of distant
      metastasis from SMG tumors.

PMID- 24456479
TI  - Validation of the Intelligibility in Context Scale as a screening tool for
      preschoolers in Hong Kong.
AB  - The Intelligibility in Context Scale (ICS) is a parent report questionnaire for
      assessing children's speech intelligibility. The original version was developed
      in English and was based on Environmental Factors identified within the
      International Classification of Functioning, Disability and Health-Children and
      Youth Version (ICF-CY). The ICS has been translated into over 30 languages,
      including Traditional Chinese (ICS-TC). The aims of the current study were to
      examine the psychometric properties of the ICS-TC with Cantonese-speaking parent-
      child dyads and to identify speech measures that were more sensitive to the ICS
      TC ratings. A total of 72 Cantonese-speaking preschoolers with (n = 39) and
      without speech sound disorders (SSD; n = 33) were recruited. Native Cantonese
      speaking parents completed the ICS-TC independently. The measure showed good
      internal consistency and test-retest reliability. Correlations with speech
      performance on the Hong Kong Cantonese Articulation Test (HKCAT), and significant
      difference in ICS-TC mean scores between the two groups provided preliminary
      support for the validity of ICS-TC and suggested that ICS-TC can differentiate
      between children with and without SSD with a large effect size of d = 0.74. The
      optimal cutoff was estimated using Receiver Operative Characteristic (ROC) curve
      analysis, giving a sensitivity of 0.70 and specificity of 0.59. ICS-TC mean
      scores showed a positive correlation with the percentage of initial consonants
      correct and negative correlation with frequency of atypical errors, and both were
      moderate in strength. Given the satisfactory psychometric properties of ICS-TC,
      it may be a valuable clinical tool for screening Cantonese-speaking preschool
      children's intelligibility.

PMID- 24456478
TI  - A cross-etiology comparison of the socio-emotional behavioral profiles associated
      with attention-deficit/hyperactivity disorder and specific language impairment.
AB  - Cross-etiology comparisons provide important information that can help
      practitioners establish criteria for differential diagnosis and tailor
      interventions towards the source of children's difficulties. This study examined
      the extent to which parent rating scales of socioemotional behavioral
      difficulties differentiate cases of attention-deficit/hyperactivity disorder
      (ADHD) from cases of specific language impairment (SLI), and typical development
      (TD). Parents of 60 children (7-8 years) completed the Child Behavior Checklist
      (Achenbach & Rescorla, 2001) and the Conners Parent Rating Scale-Revised
      (Conners, 2004). Significant differences were observed between ratings provided
      for the children with ADHD and the children with SLI and TD across several scales
      which assessed behavioral and emotional difficulties. Most of the observed
      differences between ratings provided for the SLI and TD groups were not
      significant when nonverbal IQ was treated as a covariate or when syndrome scales
      were adjusted for the presence of language and academic items. In contrast, these
      adjustments had little impact on observed differences between the children with
      ADHD and the other groups. These results highlight important and clinically
      useful differences between the scope and the scale of socioemotional behavior
      difficulties associated with ADHD and SLI.

PMID- 24456480
TI  - Delayed endoluminal vacuum therapy for rectal anastomotic leaks after rectal
      resection in a swine model: a new treatment option.
AB  - Anastomotic leaks are a dreaded surgical complication following colorectal
      operations. Creation of a temporary proximal diverting ileostomy is used in high
      risk anastomoses, however, additional surgical risk is accumulated with its
      creation and reversal. Endoluminal vacuum therapy has been shown to seal
      anastomotic defects in the prophylactic setting in a pig model and we
      hypothesized it could be utilized in a delayed fashion to rescue subjects with an
      active anastomotic leak. Yorkshire pigs underwent rectal resection, intentional
      leak confirmed by fluoroscopy, and endoluminal vacuum therapy device placement to
      low continuous suction. Following treatment, a contrast enema and necropsy was
      performed for gross and histopathology. Pigs underwent 2 (or 5) days of free
      intraperitoneal leak prior to device placement and 5 (or 7) subsequent days of
      endoluminal vacuum therapy. Six of seven early-treated pigs sealed their
      anastomotic defect, while two of the four treated pigs in this extended group
      sealed the defect. Endoluminal vacuum therapy is feasible and well tolerated in a
      pig model, and it has been shown to seal a significant number of freely leaking
      anastomoses in the early period (86%). This technology warrants further study as
      it may provide a noninvasive means to treatment of anastomotic leaks. 

PMID- 24456481
TI  - Early visual and morphologic changes after half-fluence photodynamic therapy in
      chronic central serous chorioretinopathy.
AB  - PURPOSE: To evaluate the early functional and morphologic changes in patients
      with chronic central serous chorioretinopathy (CSC) after half-fluence
      photodynamic therapy (PDT) and to compare with fellow eyes. METHODS: This
      prospective study included 32 symptomatic and 28 fellow eyes of 32 patients with
      chronic CSC. Indocyanine green angiography-guided half-fluence PDT (25 J/cm(2))
      was performed. Best-corrected visual acuity (BCVA), central foveal thickness
      (CFT), and subfoveal choroidal thickness (SFCT) were evaluated at baseline and at
      days 1, 3, 7, 30, and 60 after PDT. RESULTS: The mean age was 48.1+/-7.9 years.
      Baseline BCVA [logarithm of the minimum angle of resolution (logMAR)] improved
      from 0.56+/-0.23 to 0.54+/-0.24, 0.45+/-0.25, 0.38+/-0.23, 0.36+/-0.23, and
      0.35+/-0.21 at days 1, 3, 7, 30, and 60. (P=0.91, P=0.004, P=0.002, P=0.001, and
      P<0.001, respectively). Baseline CFT decreased from 315+/-131 to 312+/-136, 305+/
      136, 235+/-106, 174+/-44, and 165+/-36 MUm at days 1, 3, 7, 30, and 60 (P=0.41,
      P=0.33, P=0.004, P<0.001, and P<0.001, respectively). Baseline SFCT in the
      symptomatic eyes was significantly greater compared with the fellow eyes
      (P=0.002) and changed from 517+/-98 to 546+/-109, 528+/-110, 495+/-119, 462+/
      124, and 457+/-123 MUm at days 1, 3, 7, 30, and 60 (P=0.02, P=0.42, P=0.07,
      P=0.004, P=0.003, respectively). CONCLUSION: The SFCT in the symptomatic eyes was
      greater in the fellow eyes at baseline. Functional and morphological
      chorioretinal changes started in very early period of treatment. Half-fluence PDT
      for chronic CSC resulted in thinner CFT and SFCT, and also showed a significant
      improvement in visual acuity.

PMID- 24456482
TI  - Factors associated with fear of falling in people with Parkinson's disease.
AB  - BACKGROUND: This study aimed to comprehensibly investigate potential contributing
      factors to fear of falling (FOF) among people with idiopathic Parkinson's disease
      (PD). METHODS: The study included 104 people with PD. Mean (SD) age and PD
      duration were 68 (9.4) and 5 (4.2) years, respectively, and the participants' PD
      symptoms were relatively mild. FOF (the dependent variable) was investigated with
      the Swedish version of the Falls Efficacy Scale, i.e. FES(S). The first multiple
      linear regression model replicated a previous study and independent variables
      targeted: walking difficulties in daily life; freezing of gait; dyskinesia;
      fatigue; need of help in daily activities; age; PD-duration; history of
      falls/near falls and pain. Model II included also the following clinically
      assessed variables: motor symptoms, cognitive functions, gait speed, dual-task
      difficulties and functional balance performance as well as reactive postural
      responses. RESULTS: Both regression models showed that the strongest contributing
      factor to FOF was walking difficulties, i.e. explaining 60% and 64% of the
      variance in FOF-scores, respectively. Other significant independent variables in
      both models were needing help from others in daily activities and fatigue.
      Functional balance was the only clinical variable contributing additional
      significant information to model I, increasing the explained variance from 66% to
      73%. CONCLUSIONS: The results imply that one should primarily target walking
      difficulties in daily life in order to reduce FOF in people mildly affected by
      PD. This finding applies even when considering a broad variety of aspects not
      previously considered in PD-studies targeting FOF. Functional balance
      performance, dependence in daily activities, and fatigue were also independently
      associated with FOF, but to a lesser extent. Longitudinal studies are warranted
      to gain an increased understanding of predictors of FOF in PD and who is at risk
      of developing a FOF.

PMID- 24456483
TI  - Two bioactive compounds from the Chinese scorpion Buthusmartensii Karsch.
AB  - Two compounds, 3beta-acetoxyl,2,14,22-trihydroxy,19
      hydroxymethyl,9alpha,5beta,14beta-card-20(22)enolide (1) and 1,2,3,4-tetrahydro-6
      hydroxy1-5-pyrimidinecarbox-aldehyde (2), were isolated from arthropods in
      scorpion, Buthus martensii Karsch, by medium pressure liquid chromatography with
      silica gel as stationary phase and RP-HPLC analysis technology. The structures
      were elucidated on the basis of NMR spectroscopic analysis and HR-ESI-MS
      determination. It was found that (1) is a novel compound and both compounds
      showed inhibitory activities against the Gram-positive bacteria Bacillus subtilis
      (minimum inhibitory concentrations = 15 MUg/mL), with diameter of inhibition zone
      at phi = 6.0 mm (compound 1) and phi = 9.0 mm (compound 2), respectively.

PMID- 24456484
TI  - Editors' note.

PMID- 24456486
TI  - Spinal cord injury facts and figures at a glance.

PMID- 24456485
TI  - Structural and functional left ventricular impairment in subjects with chronic
      spinal cord injury and no overt cardiovascular disease.
AB  - CONTEXT: Cardiovascular disease (CVD) is the leading cause of morbidity and
      mortality in subjects with long-term spinal cord injury (SCI). More specific
      recommendations for CVD prevention in this population are needed. METHODS: One
      hundred thirty male subjects (47 subjects with SCI and 83 able-bodied persons
      (ABPs), mean age 43.89 +/- 1.9 and 45.44 +/- 12.2 years; P = 0.48) underwent
      transthoracic echocardiography (TTE). The effects of age, weight, mean arterial
      pressure (MAP) and level of physical training on cardiac adaptations were
      evaluated through multiple regression analysis. RESULTS: In subjects with SCI,
      TTE revealed increased wall thickness (P < 0.05), lower E wave, E/A ratio and
      early diastolic myocardial relaxation velocity on Tissue Doppler Imaging (TDI) (P
      < 0.05) and higher systolic myocardial contraction velocity on TDI (0.10 +/- 0.02
      vs. 0.09 +/- 0.02 m/seconds, P = 0.002) and peak systolic pressure to end
      systolic volume ratio (3.62 +/- 1.39 vs. 2.82 +/- 0.90, P < 0.001) compared with
      ABPs. Aortic diameters were larger in subjects with SCI than ABPs. Differences
      remained statistically significant even after adjustment for age, weight, MAP,
      and level of physical training. Weight and age were found to be independent
      variables that substantially affected left ventricular structure and function in
      subjects with SCI. CONCLUSIONS: Subjects with post-traumatic chronic SCI and no
      overt cardiovascular risk factors, exhibit initial left ventricular remodeling
      (as assessed by TTE) compared with ABPs. Lifestyle modifications, including
      regular physical exercise and weight control, should be implemented in all
      subjects with SCI, even at a very early stage, in order to reduce cardiovascular
      risk and prevent the development of CVD.

PMID- 24456489
TI  - Complex roles of hybrid lipids in the composition, order, and size of lipid
      membrane domains.
AB  - Hybrid lipids (HL) are phospholipids with one saturated chain and one unsaturated
      chain. HL are hypothesized to act as linactants (i.e., 2D surfactants) in cell
      membranes, reducing line tension and creating nanoscopic lipid domains. Here we
      compare three hybrid lipids of different chain unsaturation (16:0-18:1PC (POPC),
      16:0-18:2PC (PLPC), and 16:0-20:4PC (PAPC)) in their abilities to alter the
      composition, line tension, order, and compactness of lipid domains. We found that
      the liquid-ordered (Lo) and liquid-disordered (Ld) lipid domains in
      PAPC/di18:0PC(DSPC)/cholesterol and PLPC/DSPC/cholesterol mixtures are micrometer
      sized, and only the POPC/DSPC/cholesterol system has nanoscopic domains. The
      results indicate that some HLs with polyunsaturated chains are not linactants,
      and the monounsaturated POPC displays both properties of weak linactants and "Ld
      phase" lipids such as di18:1PC (DOPC). The obtained phase boundaries from giant
      unilamellar vesicles (GUV) show that both POPC and PLPC partition well in the Lo
      phases. Our MD simulations reveal that these hybrid lipids decrease the order and
      compactness of Lo domains. Thus, hybrid lipids distinguish themselves from other
      lipid groups in this combined "partitioning and loosening" ability, which could
      explain why the Lo domains of GUVs, which often do not contain HL, are more
      compact than the raft domains in cell membranes. Our line tension measurement and
      Monte Carlo simulation both show that even the monounsaturated POPC is a weak
      linactant with only modest ability to occupy domain boundaries and reduce line
      tension. A more important property of HLs is that they can reduce physical
      property differences of Lo and Ld bulk domains, which also reduces line tension
      at domain boundaries. 

PMID- 24456491
TI  - Patients' experiences in magnetic resonance imaging (MRI) and their experiences
      of breath holding techniques.
AB  - AIMS: To describe patients' experiences of magnetic resonance examination of the
      liver and their experiences of two breath-hold techniques. BACKGROUND:
      Traditionally, patients are instructed by the radiographer to hold their breath
      during the examination. Alternatively, the patient can initiate the breath hold
      and start the image acquisition. Studies have revealed that magnetic resonance
      examinations can be experienced as challenging. DESIGN: Descriptive qualitative.
      METHODS: Semi-structured interviews were conducted with 28 patients and analysed
      using qualitative content analysis. The data collection was carried out from
      autumn 2010 to spring 2011. RESULTS: The patients' main experience was that they
      felt loss of control. This was described in terms of feeling trapped, being lost
      in time and lost as a result of uncertainty. They had many questions in their
      mind that they did not ask. Although their statements often revealed no clear
      preference regarding the techniques, almost half of the patients seemed to prefer
      self-initiated breath hold, as it was easier and less stressful. Those who
      preferred the radiographer-directed technique felt more confident leaving the
      responsibility to the radiographer. In general, the patients understood the
      importance of achieving the best quality images possible. CONCLUSION: Magnetic
      resonance examination can be experienced as being in loss of control.
      Nevertheless, not all patients wished to actively participate in magnetic
      resonance examination. Some preferred to hand over the responsibility to the
      radiographer. These results can form a base for radiographers' reflections of how
      to individualize and optimize the nursing care of patients undergoing magnetic
      resonance examinations.

PMID- 24456490
TI  - Synthesis and anti-renal fibrosis activity of conformationally locked truncated 2
      hexynyl-N(6)-substituted-(N)-methanocarba-nucleosides as A3 adenosine receptor
      antagonists and partial agonists.
AB  - Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl
      substitution were synthesized to examine parallels with corresponding 4'
      thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR
      binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted
      high hA2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N(6)-cycloalkyl
      group (4d) showed excellent binding affinity at the hA3AR and was better than an
      unsubstituted free amino group (4a). A3AR affinities of 3-halobenzylamine
      derivatives 4f-4i did not differ significantly, with Ki values of 7.8-16.0 nM.
      N(6)-Methyl derivative 4b (Ki = 4.9 nM) was a highly selective, low efficacy
      partial A3AR agonist. All compounds were screened for renoprotective effects in
      human TGF-beta1-stimulated mProx tubular cells, a kidney fibrosis model. Most
      compounds strongly inhibited TGF-beta1-induced collagen I upregulation, and their
      A3AR binding affinities were proportional to antifibrotic effects; 4b was most
      potent (IC50 = 0.83 MUM), indicating its potential as a good therapeutic
      candidate for treating renal fibrosis. 

PMID- 24456493
TI  - Probing Raman enhancement in a dopamine-Ti2O4 hybrid using stretched molecular
      geometries.
AB  - Hybrids consisting of a metal oxide nanoparticle and a molecule show strong
      enhancement of Raman modes due to an interfacial charge transfer process that
      induces the formation of midgap states, thereby reducing the effective gap
      compared to that of the nanoparticle and creating the posibility of an electronic
      resonance at energies substantially lower than the nanoparticles's band gap. We
      have developed a simple methodology to mimic the presence of the nanoparticle
      through a deformation of the bond involved in the chemical binding between the
      two entities forming the hybrid. The results provide a convincing interpretative
      frame to the enhancements observed in Raman spectra when all atoms are included.
      In addition, these enhancements can be correlated to a crossing of excited
      molecular orbitals that take part in the virtual excitation associated with the
      Raman process. We illustrate our method for the dopamine-Ti2O4 hybrid using the
      most acidic molecular O-H bond as the control parameter for the deformation. 

PMID- 24456492
TI  - Depression and risk of incident asthma in adults. The CARDIA study.
AB  - RATIONALE: Asthma is associated with depression, but the temporality of the
      association has not been established. OBJECTIVES: To examine the association
      between prevalent elevated depressive symptoms and incident asthma, and between
      prevalent asthma and incident elevated depressive symptoms in a cohort of young
      and middle-aged adults. METHODS: We examined the longitudinal association between
      asthma and depressive symptoms bidirectionally in the Coronary Artery Risk
      Development in Young Adults (CARDIA) cohort. First, 3,614 participants, free of
      asthma, were classified by elevated depressive symptoms at the CARDIA Year-5 exam
      (n = 856 elevated vs. 2,758 not elevated; ages 23-35 yr) and followed for 20
      years to incident asthma. Then, 3,016 participants, free of elevated depressive
      symptoms, were classified by self-reported current asthma status (n = 188
      prevalent vs. 2,828 not prevalent) at the CARDIA Year-5 exam and followed for 20
      years until onset of elevated depressive symptoms. MEASUREMENTS AND MAIN RESULTS:
      The relative hazard of incident asthma among those with elevated depressive
      symptoms was 1.26 (95% confidence interval [CI] = 1.02-1.56) after adjustment for
      covariates. When depressive status was modeled as the total number of reports of
      elevated depressive symptoms before the onset of asthma, the adjusted hazard
      ratio was 1.15 (95% CI = 1.02-1.29). The hazard of incident elevated depressive
      symptoms for those with asthma was no different than the hazard in those without
      asthma (adjusted hazard ratio = 0.92; 95% CI = 0.70-1.20). CONCLUSIONS: This
      longitudinal observational study points to depression as a marker of risk for
      incident adult-onset asthma. On the other hand, prevalent asthma is not
      associated with incident adult-onset depression.

PMID- 24456494
TI  - Experimental observation of permeability changes in dolomite at CO2 sequestration
      conditions.
AB  - Injection of cool CO2 into geothermally warm carbonate reservoirs for storage or
      geothermal energy production may lower near-well temperature and lead to mass
      transfer along flow paths leading away from the well. To investigate this
      process, a dolomite core was subjected to a 650 h, high pressure, CO2 saturated,
      flow-through experiment. Permeability increased from 10(-15.9) to 10(-15.2) m(2)
      over the initial 216 h at 21  degrees C, decreased to 10(-16.2) m(2) over 289 h
      at 50  degrees C, largely due to thermally driven CO2 exsolution, and reached a
      final value of 10(-16.4) m(2) after 145 h at 100  degrees C due to continued
      exsolution and the onset of dolomite precipitation. Theoretical calculations show
      that CO2 exsolution results in a maximum pore space CO2 saturation of 0.5, and
      steady state relative permeabilities of CO2 and water on the order of 0.0065 and
      0.1, respectively. Post-experiment imagery reveals matrix dissolution at low
      temperatures, and subsequent filling-in of flow passages at elevated temperature.
      Geochemical calculations indicate that reservoir fluids subjected to a thermal
      gradient may exsolve and precipitate up to 200 cm(3) CO2 and 1.5 cm(3) dolomite
      per kg of water, respectively, resulting in substantial porosity and permeability
      redistribution. 

PMID- 24456497
TI  - Satisfaction with information provision is associated with baseline but not with
      follow-up quality of life among lymphoma patients: Results from the PROFILES
      registry.
AB  - BACKGROUND: Appropriate information provision is an important determinant of
      patient satisfaction and might also affect health-related quality of life (HRQoL)
      of cancer patients. The aim of this study was to examine the relationship between
      perceived information provision at baseline and HRQoL, anxiety and depression
      among lymphoma patients two years later. MATERIAL AND METHODS: This study is part
      of a longitudinal, population-based survey among all lymphoma patients diagnosed
      between 1999 and 2009 as registered in the Eindhoven Cancer Registry (southern
      part of The Netherlands). Patients between six months and 10 years after
      diagnoses received the first questionnaire including the EORTC QLQ-INFO25, EORTC
      QLQ-C30 and HADS at baseline (T1) and the second two years later (T2). All
      analyses are stratified for time since diagnosis (< 2 and >= 2 years since
      diagnosis). RESULTS: At baseline 69% of the patients (n = 1186) responded, at T2
      355 (30%) patients responded. For patients < 2 years since diagnosis, receiving
      more medical test information was associated with higher levels of cognitive
      functioning (beta = 0.46; p = 0.04) and lower levels of anxiety (beta = -0.41; p
      = 0.04) at baseline, no prospective relationships were found. For patients >= 2
      years since diagnosis, receiving more medical test information (beta = 0.20; p =
      0.03) was associated with better emotional functioning, while receiving more
      treatment information was associated with worse emotional functioning (beta = 
      0.21; p = 0.04). Among this group, satisfaction with the received information was
      associated with better functioning (beta ranging from -0.15 to -0.33; all p <
      0.05) at baseline, and these relationships remained significant prospectively for
      physical (beta = -0.13; p = 0.02) and emotional functioning (beta = -0.13; p =
      0.04) only. Stability of satisfaction with received information over time was
      associated with better emotional (beta = -0.13) and better cognitive functioning
      (beta = -0.09; p < 0.05) at T2. CONCLUSION: The present study showed that
      satisfaction with received information among lymphoma patients was associated
      with better HRQoL at baseline (only for patients >= 2 years since diagnosis), but
      not at follow-up when corrected for baseline HRQoL.

PMID- 24456499
TI  - Preferences for potential innovations in non-invasive colorectal cancer
      screening: A labeled discrete choice experiment for a Dutch screening campaign.
AB  - BACKGROUND: The introduction of innovative non-invasive screening tests (e.g.
      tests based on stool and blood samples or both) may be a solution to increase
      colorectal cancer (CRC) screening uptake. However, preferences for these non
      invasive screening tests have not been investigated in great detail yet. The
      purpose of this article therefore is to elicit individuals' preferences for
      different non-invasive screening tests in a Dutch screening campaign context.
      MATERIAL AND METHODS: We investigate preferences by means of a labeled discrete
      choice experiment. Data of 815 individuals, aged 55-75 years, are used in the
      analysis. RESULTS: Multinomial logit model analysis showed that the combi-test is
      generally preferred over the blood-test and the (currently available) stool-test.
      Furthermore, besides the large effect of screening test type, there are
      significant differences in preference depending on participants' socio
      demographic background. Finally, the analysis showed a significant positive
      effect on screening test choice for the attributes sensitivity, risk reduction,
      and level of evidence and a non-significant effect for the attribute unnecessary
      follow-up test. CONCLUSION: Introducing new non-invasive screening tests that are
      based on a combination of stool and blood samples (or blood sample only) has the
      potential to increase CRC screening participation compared to the current
      standard stool-based test.

PMID- 24456498
TI  - Risk of disability pension for patients diagnosed with haematological
      malignancies: a register-based cohort study.
AB  - Patients with haematological malignancies are at increased risk of experiencing
      work-related problems. The aims of this study were to compare the risk of
      disability pension (DP) among patients diagnosed with eight subtypes of
      haematological malignancies to a reference cohort, and to determine if relative
      risks differ between these subtypes; to evaluate the influence of socioeconomic
      factors, demographic factors, and clinical factors on the risk of DP; and to
      investigate if these associations differ between the reference cohort and the
      patient cohort. MATERIAL AND METHODS: We combined data from national registers on
      Danish patients diagnosed with haematological malignancies between 2000 and 2007
      and a reference cohort without a history of these diseases. A total of 3194
      patients and 28 627 reference individuals were followed until DP, emigration, old
      age pension or anticipatory pension, death or 26 February 2012, whichever came
      first. RESULTS: A total of 550 (17%) patients and 1511 (5%) reference individuals
      were granted DP. Age- and gender-adjusted relative risks differed significantly
      between the subgroups of haematological malignancies and ranged from 2.64 (95% CI
      1.84-3.78) for patients with Hodgkin lymphoma to 12.53 (95% CI 10.57-14.85) for
      patients with multiple myeloma. In the patient cohort we found that gender, age,
      comorbidity, ethnicity, educational level, household income, history of long-term
      sick leave, and need of treatment with anxiolytics or antidepressants after
      diagnosis were associated with receiving DP. However, most of these associations
      were stronger in the reference cohort. CONCLUSION: All eight subtypes of
      haematological malignancies were associated with an increased risk of DP compared
      to the reference cohort. The relative risks differed according to subtype, and
      patients with multiple myeloma had the highest risk of DP. Furthermore, most
      socioeconomic, demographic and clinical factors had a stronger impact on the risk
      of DP in the reference cohort than in the patient cohort.

PMID- 24456500
TI  - Radiation-induced lung injury after concurrent neoadjuvant chemoradiotherapy for
      locally advanced breast cancer.

PMID- 24456501
TI  - Simultaneous acute myeloid leukemia and mesothelioma diagnoses in a long-term
      survivor of the 1984 Bhopal gas leak.

PMID- 24456502
TI  - Impact of advancing age on treatment and outcomes in anal cancer.
AB  - BACKGROUND: Chemoradiotherapy (CRT) for squamous cell carcinoma of the anus
      (SCCA) may cause significant toxicity, and concerns exist about its tolerability
      in the elderly. The authors compared tolerability and outcomes across the age
      groups following CRT for SCCA. METHODS: Single-institution retrospective analysis
      of patients with localized SCCA treated with CRT. CRT was standardized at 50.4-54
      Gy, with concurrent infusional 5-fluorouracil and mitomycin C. Patients were
      arbitrarily categorized into three groups: Group 1 - age < 50 years; Group 2 -
      age >= 50 and < 70 years; and Group 3 - age >= 70 years. RESULTS: Of 284 patients
      identified, 278 were evaluable. The number of patients in each age group was:
      Group 1 - 51; Group 2 - 140; and Group 3 - 93. Baseline and treatment
      characteristics, tumor stage, rates of overall acute toxicity, need for unplanned
      treatment breaks and chemotherapy delivery were largely similar across the age
      groups. However, nine patients in Group 3 did not complete CRT, compared with
      five and none in Groups 1 and 2, respectively (p = 0.006). In addition, five
      patients in Group 3 had diarrhea requiring treatment break, compared with none in
      the other two groups (p = 0.004). At a median follow-up 5.3 years, there was no
      significant difference in overall survival (p = 0.11), disease-free survival (p =
      0.22) or local-recurrence free survival (p = 0.34), across the three age groups.
      CONCLUSIONS: CRT is safe and tolerable in the elderly age group, and provides
      equivalent disease control rates compared with the younger age group. Age alone
      should therefore not preclude aggressive curative treatment.

PMID- 24456503
TI  - Durable stabilization of three chordoma cases by bevacizumab and erlotinib.

PMID- 24456504
TI  - Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide
      followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma
      multiforme: A randomized phase II study.
AB  - BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant
      temozolomide is standard therapy in newly diagnosed glioblastoma multiforme
      (GBM). Bevacizumab combined with irinotecan produces impressive response rates in
      recurrent GBM. In a randomized phase II study, we investigated the efficacy of
      neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab
      combined with temozolomide (Bev-Tem) before, during and after radiotherapy in
      newly diagnosed GBM. MATERIAL AND METHODS: After surgery, patients were
      randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard
      radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by
      adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and
      irinotecan were given every 14 days before, during and after radiotherapy. Bev
      Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days
      every four weeks before and after radiotherapy and once daily during
      radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy
      and a pre-specified response rate of 30% or more was considered of interest for
      future studies. Secondary endpoints were progression-free survival (PFS) and
      toxicity. RESULTS: The response rate was 32% (95% CI 17-51%) for Bev-Tem (n = 32)
      and 23% (95% CI 9-44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and
      7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more
      frequent with Bev-Tem including one death from febrile neutropenia whereas non
      hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the
      pre-specified level of activity of interest. Our results did not indicate any
      benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of
      response and PFS.

PMID- 24456505
TI  - European reference values for the quality of life questionnaire EORTC QLQ-C30:
      Results of a German investigation and a summarizing analysis of six European
      general population normative studies.
AB  - BACKGROUND: The aims of this study are to present the results of a new general
      population normative study of the quality of life questionnaire EORTC QLQ-C30 and
      to give European reference values averaged across six studies. METHODS: The
      empirical study was based on a representative sample of the German adult
      population (N = 2448). The subjects were asked to fill in several questionnaires,
      one of them being the EORTC QLQ-C30. RESULTS: EORTC QLQ-C30 mean scores of this
      sample indicated slightly better quality of life (QoL) than in previous European
      studies. QoL decreased with age, but there were only small gender differences.
      The mean scores were compared with the age and gender adjusted scores of five
      other European normative studies from Sweden, the Netherlands, Norway, and
      Germany (N between 1731 and 4910). Finally, the data of these five studies and
      the new study were combined to arrive at averaged European normative values for
      the scales and the symptom items of the questionnaire. CONCLUSION: The reference
      values of the scales pooled across six European studies (N = 16 151) can be used
      as general population references for QoL scores of cancer patients.

PMID- 24456506
TI  - Community-based screening for obstetric fistula in Nigeria: a novel approach.
AB  - BACKGROUND: Obstetric fistula continues to have devastating effects on the
      physical, social, and economic lives of thousands of women in many low-resource
      settings. Governments require credible estimates of the backlog of existing cases
      requiring care to effectively plan for the treatment of fistula cases. Our study
      aims to quantify the backlog of obstetric fistula cases within two states via
      community-based screenings and to assess the questions in the Demographic Health
      Survey (DHS) fistula module. METHODS: The screening sites, all lower level health
      facilities, were selected based on their geographic coverage, prior relationships
      with the communities and availability of fistula surgery facilities in the state.
      This cross-sectional study included women who presented for fistula screenings at
      study facilities based on their perceived fistula-like symptoms. Research
      assistants administered the pre-screening questionnaire. Nurse-midwives then
      conducted a medical exam. Univariate and bivariate analyses are presented.
      RESULTS: A total of 268 women attended the screenings. Based on the pre-screening
      interview, the backlog of fistula cases reported was 75 (28% of women screened).
      The backlog identified after the medical exam was 26 fistula cases (29.5% of
      women screened) in Kebbi State sites and 12 cases in Cross River State sites
      (6.7%). Verification assessment showed that the DHS questionnaire had 92%
      sensitivity, 83% specificity with 47% positive predictive value and 98% negative
      predictive value for identifying women afflicted by fistula among women who came
      for the screenings. CONCLUSIONS: This methodology, involving effective, locally
      appropriate messaging and community outreach followed up with medical examination
      by nurse-midwives at lower level facilities, is challenging, but represents a
      promising approach to identify the backlog of women needing surgery and to link
      them with surgical facilities.

PMID- 24456508
TI  - Strengthening community involvement in grant review: insights from the Community
      University Research Partnership (CURES) pilot review process.
AB  - In 2007, the Michigan Institute for Clinical and Health Research (MICHR) at the
      University of Michigan received a Clinical and Translational Science Award
      (CTSA). Within MICHR, the Community Engagement (CE) program supports partnership
      efforts between researchers, practitioners, and community-based organizations in
      specific focal communities throughout Michigan. A key component of the CE program
      is the Community Engagement Coordinating Council, a group that provides input and
      guidance on program priorities, strategic planning, and reviews pilot funding
      proposals for community-academic partnerships. This paper will describe a unique
      MICHR pilot funding mechanism for Community-University Research Partnerships
      (CURES) with an emphasis on the ways that community partners are involved in the
      review process, as well as the benefits, challenges, and insights gained over 5
      years of pilot review. There is a growing need for community involvement and
      expertise in review of funding proposals for community-engaged research at both
      institutional and federal levels. The CURES pilot review process is one example
      of an institutional effort to engage community partners in university funding
      decisions and has demonstrated clear benefit toward accomplishing the aims of the
      CTSA. 

PMID- 24456510
TI  - The efficacy of incentives to motivate continued fitness-center attendance in
      college first-year students: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether fitness-center attendance established with the
      provision of weekly monetary incentives persisted after the discontinuation, or
      decreased frequency, of incentives. PARTICIPANTS: One hundred seventeen first
      year college students participated during the 2011-2012 academic year. METHODS: A
      randomized controlled trial with control, discontinued-incentive, and continued
      incentive conditions was conducted. During fall semester, students in incentive
      conditions received weekly monetary payments for meeting fitness-center
      attendance goals. During spring semester, discontinued-incentive condition
      participants no longer received incentives, whereas continued-incentive condition
      participants received payments on a variable-interval schedule. ID-card
      attendance records tracked fitness-center attendance. RESULTS: Goal completion
      decreased from 63% in the incentive groups during the fall semester to 3% in the
      discontinued-incentive condition, and 39% in the continued-incentive condition
      during the spring semester. There was not a significant interaction between
      condition and body mass index change, F(6, 332) = 0.67, p = .68. CONCLUSION:
      Incentive discontinuation resulted in students no longer meeting fitness-center
      attendance goals. A variable-interval reward schedule better maintained
      attendance.

PMID- 24456507
TI  - The TRANSPLANTA collection of Arabidopsis lines: a resource for functional
      analysis of transcription factors based on their conditional overexpression.
AB  - Transcription factors (TFs) are key regulators of gene expression in all
      organisms. In eukaryotes, TFs are often represented by functionally redundant
      members of large gene families. Overexpression might prove a means to unveil the
      biological functions of redundant TFs; however, constitutive overexpression of
      TFs frequently causes severe developmental defects, preventing their functional
      characterization. Conditional overexpression strategies help to overcome this
      problem. Here, we report on the TRANSPLANTA collection of Arabidopsis lines, each
      expressing one of 949 TFs under the control of a beta-estradiol-inducible
      promoter. Thus far, 1636 independent homozygous lines, representing an average of
      2.6 lines for every TF, have been produced for the inducible expression of 634
      TFs. Along with a GUS-GFP reporter, randomly selected TRANSPLANTA lines were
      tested and confirmed for conditional transgene expression upon beta-estradiol
      treatment. As a proof of concept for the exploitation of this resource, beta
      estradiol-induced proliferation of root hairs, dark-induced senescence,
      anthocyanin accumulation and dwarfism were observed in lines conditionally
      expressing full-length cDNAs encoding RHD6, WRKY22, MYB123/TT2 and MYB26,
      respectively, in agreement with previously reported phenotypes conferred by these
      TFs. Further screening performed with other TRANSPLANTA lines allowed the
      identification of TFs involved in different plant biological processes,
      illustrating that the collection is a powerful resource for the functional
      characterization of TFs. For instance, ANAC058 and a TINY/AP2 TF were identified
      as modulators of ABA-mediated germination potential, and RAP2.10/DEAR4 was
      identified as a regulator of cell death in the hypocotyl-root transition zone.
      Seeds of TRANSPLANTA lines have been deposited at the Nottingham Arabidopsis
      Stock Centre for further distribution. 

PMID- 24456509
TI  - Hormonal contraception in women with migraine: is progestogen-only contraception
      a better choice?
AB  - A significant number of women with migraine has to face the choice of reliable
      hormonal contraception during their fertile life. Combined hormonal
      contraceptives (CHCs) may be used in the majority of women with headache and
      migraine. However, they carry a small, but significant vascular risk, especially
      in migraine with aura (MA) and, eventually in migraine without aura (MO) with
      additional risk factors for stroke (smoking, hypertension, diabetes,
      hyperlipidemia and thrombophilia, age over 35 years). Guidelines recommend
      progestogen-only contraception as an alternative safer option because it does not
      seem to be associated with an increased risk of venous thromboembolism (VTE) and
      ischemic stroke. Potentially, the maintenance of stable estrogen level by the
      administration of progestins in ovulation inhibiting dosages may have a positive
      influence of nociceptive threshold in women with migraine. Preliminary evidences
      based on headache diaries in migraineurs suggest that the progestin-only pill
      containing desogestrel 75MUg has a positive effect on the course of both MA and
      MO in the majority of women, reducing the number of days with migraine, the
      number of analgesics and the intensity of associated symptoms. Further
      prospective trials have to be performed to confirm that progestogen-only
      contraception may be a better option for the management of both migraine and
      birth control. Differences between MA and MO should also be taken into account in
      further studies.

PMID- 24456511
TI  - Implementing an audience-specific small-group gatekeeper training program to
      respond to suicide risk among college students: a case study.
AB  - OBJECTIVE: This case study evaluated the effectiveness of an audience-specific,
      single-session, small-group interactive gatekeeper training program conducted at
      a large northeastern public university. PARTICIPANTS: Participants were 335
      faculty, staff, and students completing gatekeeper training programs tailored to
      their group needs. METHODS: Baseline assessments of knowledge about suicide, risk
      factors, resources for assistance, and comfort in intervening with a student in
      distress were administered to participants prior to the small-group training
      sessions; posttest assessments of knowledge and comfort in intervening with
      students in distress were administered upon completion of training and at 3-month
      follow-up. RESULTS: There was a statistically significant increase in knowledge
      and comfort upon completion of training for both faculty/staff and student
      groups, although degradation of training effects at 3-month follow-up was
      evident. CONCLUSIONS: There are benefits associated with the implementation of
      audience-specific gatekeeper training programs. Booster training sessions to
      address skill degradation over time are recommended.

PMID- 24456512
TI  - A randomized trial investigating the effect of a brief lifestyle intervention on
      freshman-year weight gain.
AB  - OBJECTIVE: The current study was a randomized controlled trial investigating the
      effect of an innovative, short-term lifestyle intervention on weight gain in
      female freshman college students. PARTICIPANTS: Ninety-five freshmen were
      recruited from a large public university in the United States. METHODS:
      Participants completed baseline assessments and were randomized to a 5-session, 4
      week intervention or wait-list control, with assessments at posttest and 3-month
      follow-up. RESULTS: The hypothesized time by group interaction was not
      significant, p = .393; however, trends suggested that control participants
      maintained baseline weight, whereas intervention participants lost -2.07 kg by
      posttest but regained 1.05 kg at follow-up. Significantly more intervention
      participants (47.0%) decreased their daily caloric intake by >= 200 kcal compared
      with control (31.7%), p = .050. CONCLUSION: Brief intervention to prevent weight
      gain was not effective in this sample. Future studies should investigate
      lengthening the intervention to enhance effectiveness and increasing recruitment
      to improve statistical power.

PMID- 24456513
TI  - Policy compliance of smokers on a tobacco-free university campus.
AB  - OBJECTIVES: To explore factors influencing compliance with campus tobacco
      policies and strategies to increase compliance. PARTICIPANTS: Sixty tobacco
      smokers (April 2012). METHODS: A 22-item intercept-interview with closed- and
      open-ended questions was conducted with smokers in adjacent compliant and
      noncompliant areas at 1 university with a 100% tobacco ban. Data were analyzed
      using descriptive statistics and content analysis. RESULTS: Most reported that
      the smoking policy was not enforced. Noncompliant smokers had less knowledge of
      locations where tobacco use was permitted and were more likely to identify their
      smoking location as compliant and had knowingly violated the policy. Choice of
      location to smoke was related to convenience and a desire to follow the policy.
      Smokers recommended consequences for noncompliance and structures that
      accommodated smoking to increase adherence to the tobacco ban. CONCLUSIONS:
      Additional education, environmental, and contingency strategies are needed to
      increase compliance with the policy banning tobacco use on this campus.

PMID- 24456514
TI  - A novel, self-guided, home-based intervention to improve condom use among young
      men who have sex with men.
AB  - OBJECTIVE: This pilot study tested the efficacy of a brief, novel, theory-driven,
      self-guided, home-based intervention designed to promote condom use among young
      men who have sex with men (YMSM). PARTICIPANTS: Thirty YMSM were recruited from a
      large public US midwestern university during spring of 2012. METHODS: The
      intervention was tested using a repeated measures design with the primary follow
      up assessment occurring 6 weeks after enrollment. RESULTS: Forty-five percent of
      men reported a reduced frequency of unprotected insertive penile-anal intercourse
      in the past 30 days compared with baseline (p = .01). Consistency of condom use
      improved (p = .013), as did motivation to use condoms correctly, condom use self
      efficacy, and condom attitudes. All participants indicated that they were glad
      they participated, would recommend the program, and that overall, they had liked
      the program. CONCLUSIONS: This pilot study supports an expanded trial of this
      intervention with MSM at high-risk of acquiring human immunodeficiency
      virus/sexually transmitted infections (HIV/STIs).

PMID- 24456516
TI  - Colorless triphenylamine-based aliphatic thermoset epoxy for multicolored and
      near-infrared electrochromic applications.
AB  - In this study, two novel colorless thermoset epoxy resins with anodically
      electrochromism were prepared from the thermal curing of two triphenylamine-based
      diamine monomers, 4,4'-diamino-4"-methoxytriphenylamine (1) and N,N'-bis(4
      aminophenyl)-N,N'-di(4-methoxylphenyl)-1,4-phenylenediamine (2) with aliphatic
      epoxy triglycidyl isocyanurate, respectively. The resulting thermoset epoxy
      resins showed excellent softening temperature (Ts, 270 and 280  degrees C) due to
      the rigid structure and highly crosslinking density. In addition, novel colorless
      epoxy resin films revealed good reversible electrochemical oxidation and
      interesting multi-electrochromic behavior with high contrast ratio both in
      visible and near-infrared regions. The aliphatic thermoset epoxy resins also
      exhibited high transparency in visible region as colorless and great potential
      for practical electrochromic applications. 

PMID- 24456515
TI  - Social facilitation expectancies for smoking: psychometric properties of a new
      measure.
AB  - OBJECTIVE: Expectancies about social outcomes for smoking are relevant to college
      student smokers, who frequently report "social smoking." A new measure, the
      Social Facilitation Expectancies (SFE) scale, was developed to assess these
      beliefs. PARTICIPANTS: The SFE was administered to undergraduate college student
      smokers (N = 1,096; study completed in May 2011). METHODS: Items were scored on a
      5-point scale with a summed total score. The sample was randomly split and
      principle axis factoring and confirmatory factor analysis applied to determine
      scale structure. The structure was tested across sex and smoking groups and
      validation analyses were conducted. RESULTS: A 9-item, 1-factor scale was
      replicated within each group. Higher SFE scores were observed among those with
      greater smoking experience and higher scores were associated with greater
      endorsement of other smoking-related beliefs. CONCLUSIONS: These preliminary
      findings provide support for the sound psychometric properties of this measure
      for use with young adult college students.

PMID- 24456518
TI  - Multi-scale analysis of segmental outflow patterns in human trabecular meshwork
      with changing intraocular pressure.
AB  - PURPOSE: Aqueous humor filtration in the trabecular meshwork is believed to be
      non-uniform or "segmental" such that only a fraction of trabecular meshwork is
      filtration-active at any given instant. The goal was to quantify the filtration
      active fraction of human trabecular meshwork and to determine how filtration
      patterns change with outflow facility and intraocular pressure (IOP). METHODS:
      Six pair of enucleated human eyes were perfused with fluorescent tracer
      microspheres (0.2 MUm) at 7 or 30 mmHg. Tracer patterns were imaged over the
      "macro-scale" (0.1-10 mm) using epifluorescence microscopy and "micro-scale" (10
      100 MUm) using confocal microscopy. Quantitative image analysis was used to
      measure the tracer-labeled fraction and to examine co-localization with
      trabecular pigmentation and the location of collector channel ostia. RESULTS:
      Tracer distribution was segmental over both macro-scale and micro-scale
      dimensions. No more than approximately one-third of the trabecular meshwork
      appeared to be filtration-active on the macro scale (29%+/-5%; mean+/-SD) and
      micro scale (21%+/-6%). There was weak co-localization between macro-scale tracer
      intensity and pigmentation (r=0.17, P=0.017), and collector channel ostia tended
      to coincide with regions of high macro-scale tracer intensity. Tracer patterns
      were relatively insensitive to changing IOP over hour-long time scales and did
      not correlate with outflow facility. CONCLUSIONS: Filtration patterns in human
      trabecular meshwork appear segmental over both macro-scale and micro-scale
      dimensions, with only approximately one-third of the trabecular meshwork actively
      contributing to outflow. Segmental outflow may limit the efficacy of outflow
      drugs by preventing delivery to non-filtering trabecular regions that may
      contribute the most to outflow obstruction in glaucoma.

PMID- 24456519
TI  - Histomorphologic characteristics of bisphosphonate-related osteonecrosis of the
      jaw.
AB  - BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a known
      side effect of the therapy with bisphosphonates. No specific pathologic aspects
      or histological features are included in the most current definition. This study
      investigates characteristics of BRONJ with a special emphasis on histomorphologic
      aspects, evaluating the role of Actinomyces spp. as well as other disease
      promoting factors in a formal pathogenetic context. METHODS: We investigated 23
      patients (14 female, nine male; mean age: 66 +/- 11.8 years) who received
      bisphosphonates with a gender- /age-matched control group. Tissue specimens were
      treated according to local standards and analyzed histologically. RESULTS: In 18
      (78.3%) BRONJ cases, we found Actinomyces spp. colonies. Bone remodeling could be
      found in three specimens (13%). Eight specimens (34.8%) showed signs of
      epithelial proliferation. Analysis of dental treatment before the onset of BRONJ
      did not reveal significant differences (P > 0.20). In 10 patients (83%; P > 0.05)
      of the reported cases a relationship between dental treatment and the occurrence
      of a purulent bone necrosis could be observed. Statistically significant
      differences in thickness of trabeculae were detected between the two study groups
      (P = 0.04). CONCLUSIONS: This study demonstrates the important influence of the
      osteoblast-osteoclast balance in a histomorphologic analysis. Together with
      cofactors, which are able to trigger the onset of BRONJ, a new pathogenesis model
      was developed.

PMID- 24456520
TI  - Phonological development of first language isiXhosa-speaking children aged 3;0
      6;0 years: a descriptive cross-sectional study.
AB  - Standardized assessments of children's isiXhosa phonology have not yet been
      developed and there is limited information about developmental norms in this
      language. This article reports on the phonological development of 24 typically
      developing first language isiXhosa-speaking children aged 3;0-6;0 years, in Cape
      Town, South Africa. The order and age of acquisition of isiXhosa phonemes,
      emergence and elimination of phonological processes and percentage consonants and
      vowels correct are described. A set of culturally and linguistically appropriate
      pictures was used to elicit single word responses that were recorded and
      transcribed. The study found that children had acquired most isiXhosa phonemes by
      3;0 years although aspirated plosives, affricates, fricatives and clicks were
      still developing. In particular, the affricates and aspirated plosives were still
      developing in the 5-year-old children in this sample, suggesting that these may
      be the latest acquired segments. Children were able to produce basic word shapes
      by 3;0 years, but some of the words of 4-6 syllables were still being mastered by
      the 4- and 5-year-old children. Phonological processes that have been well
      documented for other languages were used by children in this sample (e.g.
      deaffrication, stopping and gliding of liquids). Findings presented for this pre
      school-aged sample are related to theories of phonological acquisition to provide
      normative data on phonological development in isiXhosa-speaking children.

PMID- 24456521
TI  - An insight into the curdione biotransformation pathway by Aspergillus niger.
AB  - Curdione (1), a sesquiterpene with a germacrane skeleton from rhizomes of Curcuma
      wenyujin, has attracted attention due to its important pharmacological
      properties. Herein, we investigated the chemo-biotransformation of curdione (1)
      systematically using Aspergillus niger AS 3.739. Regio- and stereoselective
      hydroxylation of curdione with filamentous fungus A. niger AS 3.739 led to seven
      metabolites including four new compounds 3alpha-hydroxycurcumalactone, 2beta
      hydroxycurcumalactone, (10S)-9,10-dihydroxy-curcumalactone and (10R)-9,10
      dihydroxy-curcumalactone. Their structures were determined by spectroscopic
      techniques including two-dimensional NMR and TOF-MS (Time of Flight Mass
      Spectrometry). Based upon the analysis of biological and chemical conversions of
      curdione, a tentative metabolic pathway via chemo-bio cascade reactions is
      proposed in A. niger system, which provides an insight into the corresponding
      metabolism of curdione in animal systems. In addition, experiments with selected
      monooxygenase inhibitors suggest that cytochrome P450 monooxygenase played a
      crucial role in the hydroxylation of curdione. 

PMID- 24456522
TI  - Possible mechanisms responsible for absence of a retrotransposon family on a
      plant Y chromosome.
AB  - Some transposable elements (TEs) show extraordinary variance in abundance along
      sex chromosomes but the mechanisms responsible for this variance are unknown.
      Here, we studied Ogre long terminal repeat (LTR) retrotransposons in Silene
      latifolia, a dioecious plant with evolutionarily young heteromorphic sex
      chromosomes. Ogre elements are ubiquitous in the S. latifolia genome but
      surprisingly absent on the Y chromosome. Bacterial artificial chromosome (BAC)
      library analysis and fluorescence in situ hybridization (FISH) were used to
      determine Ogre structure and chromosomal localization. Next generation sequencing
      (NGS) data were analysed to assess the transcription level and abundance of small
      RNAs. Methylation of Ogres was determined by bisulphite sequencing. Phylogenetic
      analysis was used to determine mobilization time and selection forces acting on
      Ogre elements. We characterized three Ogre families ubiquitous in the S.
      latifolia genome. One family is nearly absent on the Y chromosome despite all the
      families having similar structures and spreading mechanisms. We showed that Ogre
      retrotransposons evolved before sex chromosomes appeared but were mobilized after
      formation of the Y chromosome. Our data suggest that the absence of one Ogre
      family on the Y chromosome may be caused by 24-nucleotide (24-nt) small RNA
      mediated silencing leading to female-specific spreading. Our findings highlight
      epigenetic silencing mechanisms as potentially crucial factors in sex-specific
      spreading of some TEs, but other possible mechanisms are also discussed. 

PMID- 24456523
TI  - Anion-pi catalysis.
AB  - The introduction of new noncovalent interactions to build functional systems is
      of fundamental importance. We here report experimental and theoretical evidence
      that anion-pi interactions can contribute to catalysis. The Kemp elimination is
      used as a classical tool to discover conceptually innovative catalysts for
      reactions with anionic transition states. For anion-pi catalysis, a carboxylate
      base and a solubilizer are covalently attached to the pi-acidic surface of
      naphthalenediimides. On these pi-acidic surfaces, transition-state stabilizations
      up to DeltaDeltaGTS = 31.8 +/- 0.4 kJ mol(-1) are found. This value corresponds
      to a transition-state recognition of KTS = 2.7 +/- 0.5 MUM and a catalytic
      proficiency of 3.8 * 10(5) M(-1). Significantly increasing transition-state
      stabilization with increasing pi-acidity of the catalyst, observed for two
      separate series, demonstrates the existence of "anion-pi catalysis." In sharp
      contrast, increasing pi-acidity of the best naphthalenediimide catalysts does not
      influence the more than 12 000-times weaker substrate recognition (KM = 34.5 +/-
      1.6 MUM). Together with the disappearance of Michaelis-Menten kinetics on the
      expanded pi-surfaces of perylenediimides, this finding supports that
      contributions from pi-pi interactions are not very important for anion-pi
      catalysis. The linker between the pi-acidic surface and the carboxylate base
      strongly influences activity. Insufficient length and flexibility cause
      incompatibility with saturation kinetics. Moreover, preorganizing linkers do not
      improve catalysis much, suggesting that the ideal positioning of the carboxylate
      base on the pi-acidic surface is achieved by intramolecular anion-pi interactions
      rather than by an optimized structure of the linker. Computational simulations
      are in excellent agreement with experimental results. They confirm, inter alia,
      that the stabilization of the anionic transition states (but not the neutral
      ground states) increases with the pi-acidity of the catalysts, i.e., the
      existence of anion-pi catalysis. Preliminary results on the general significance
      of anion-pi catalysis beyond the Kemp elimination are briefly discussed. 

PMID- 24456524
TI  - Frictional dissipation in a polymer bilayer system.
AB  - Sliding friction between a silicon tip and a polymer bilayer system consisting of
      a polystyrene (PS) film covered with a few-nanometers-thick capping layer of hard
      plasma polymer is studied using friction force microscopy. The system was chosen
      to enable subsurface dissipation channels to be distinguished from surface
      friction. Frictional energy dissipation in the underlayer can be identified
      through the kinetics of the polymer relaxation modes that we measured using
      nanoscale friction experiments as a function of sample temperature, scanning
      velocity, and applied load. We found a strong nonlinear increase in friction as a
      function of applied load around the glass-transition temperature of the PS
      underlayer. This behavior is a clear signature of frictional dissipation
      occurring in the volume of the polystyrene layer, well below the surface of the
      sample. The time-temperature kinetics associated with frictional energy
      dissipation into the PS was found to be in agreement with the known material
      properties of PS. Moreover, the data was found to support the hypothesis that the
      observed friction can be understood as the sum of friction resulting from the
      relaxation process in the polymer underlayer induced by stress due to the sliding
      of the tip and a second term associated with dissipation due to sliding friction
      on the capping layer. 

PMID- 24456525
TI  - Flavonolignans from Aspergillus iizukae, a fungal endophyte of milk thistle
      (Silybum marianum).
AB  - Silybin A (1), silybin B (2), and isosilybin A (3), three of the seven
      flavonolignans that constitute silymarin, an extract of the fruits of milk
      thistle (Silybum marianum), were detected for the first time from a fungal
      endophyte, Aspergillus iizukae, isolated from the surface-sterilized leaves of S.
      marianum. The flavonolignans were identified using a UPLC-PDA-HRMS-MS/MS method
      by matching retention times, HRMS, and MS/MS data with authentic reference
      compounds. Attenuation of flavonolignan production was observed following
      successive subculturing of the original flavonolignan-producing culture, as is
      often the case with endophytes that produce plant-based secondary metabolites.
      However, production of 1 and 2 resumed when attenuated spores were harvested from
      cultures grown on a medium to which autoclaved leaves of S. marianum were added.
      The cycle of attenuation followed by resumed biosynthesis of these flavonolignans
      was replicated in triplicate. 

PMID- 24456526
TI  - Use of white blood cell counts to predict metabolic syndrome in the elderly: a 4
      year longitudinal study.
AB  - BACKGROUND: The white blood cell (WBC) count was one of the first inflammatory
      markers associated with metabolic syndrome (MetS). Recently, two longitudinal
      studies have demonstrated a cause and effect relationship between MetS and WBC
      counts among middle-aged adults. However, no study has used WBC cutoff values to
      predict MetS in the elderly. METHODS: Subjects who underwent routine health
      checkups, and were above 60 years of age, were enrolled. All subjects were
      followed-up until they developed MetS or until 4 years from the date of entry,
      whichever came earlier. Of the 4539 subjects eligible for enrollment, 3428
      subjects comprised the study group and 1111 subjects comprised the validation
      group. RESULTS: WBC counts were significantly different between subjects with and
      without MetS in both genders. Using the ROC curve, WBC cutoff values of 5.7 *
      10(3)/ul in males and 5.0 * 10(3)/ul in females were associated with the
      increased risk of developing MetS (all p values <0.001). Using these WBC cutoff
      values, the hazard ratio (HR) for females was significant in both the study group
      and validation group. However, the HR for males failed significance in the
      validation group. Kaplan-Meier plots and kappa coefficients confirmed that the
      WBC cutoff value could predict development of MetS in women but not in men.
      CONCLUSIONS: The association between WBC count and MetS was gender specific. A
      WBC cutoff value greater than 5.0 10(3)/ul may predict the development of MetS in
      elderly women.

PMID- 24456527
TI  - FRAX calculator and Garvan nomogram in male osteoporotic population.
AB  - PURPOSE: The aim of the study was the presentation of osteoporotic fracture
      prediction in men. METHODS: Eight-hundred and one men at the mean age of 70.8 +/-
      9.31 years were examined. The 10-year fracture prediction was established, using
      the FRAX calculator and Garvan nomogram. RESULTS: The mean value for any fracture
      and hip fracture probabilities for FRAX were 7.26 +/- 5.4% and 3.68 +/- 4.25%,
      respectively. For Garvan fracture, risk values were 26.44 +/- 23.83% and 12.02 +/
      18.1%. The mean conformity for any fracture and hip fracture prediction for
      threshold of 20% (any fracture) and 3% (hip fracture) between Garvan and FRAX
      values was 55.8% (kappa 0.041) and 79.65% (kappa 0.599), respectively. ROC
      analyses showed the following areas under the ROC curves (AUC) for any fractures:
      FRAX 0.808 and Garvan nomogram 0.843 (p = 0.059). The AUC values for hip
      fractures were 0.748 for Garvan nomogram and for 0.749 FRAX, and did not differ.
      On the base of ROC data, the cut-off values with best accuracy to predict
      fractures for both methods were established. The conformity between methods for
      thresholds indicated by ROC analysis was 72.5% (kappa 0.435) for any and 77.7%
      (kappa 0.543) for hip fractures. CONCLUSION: The conformities between FRAX and
      Garvan in regard to hip fracture prediction were acceptable for a threshold of 3%
      and thresholds derived by ROC analysis, while for any fracture we recommend to
      use thresholds established by ROC analysis. This may suggest that the use of
      "universal" cut-off points is probably misleading.

PMID- 24456528
TI  - Riboflavin photosensitized oxidation of myoglobin.
AB  - The reaction of the fresh meat pigment oxymyoglobin, MbFe(II)O2, and its oxidized
      form metmyoglobin, MbFe(III), with triplet-state riboflavin involves the pigment
      protein, which is oxidatively cleaved or dimerized as shown by SDS-PAGE and
      Western blotting. The overall rate constant for oxidation of MbFe(II)O2 by 3Rib
      is (3.0 +/- 0.5) * 109 L.mol-1.s-1 and (3.1 +/- 0.4) * 109 L.mol-1.s-1 for
      MbFe(III) in phosphate buffer of pH 7.4 at 25  degrees C as determined by laser
      flash photolysis. The high rates are rationalized by ground state hydrophobic
      interactions as detected as static quenching of fluorescence from singlet-excited
      state riboflavin by myoglobins using time-resolved fluorescence spectroscopy and
      a Stern-Volmer approach. Binding of riboflavin to MbFe(III) has K(a) = (1.2 +/-
      0.2) * 104 mol.L-1 with DeltaH degrees  = -112 +/- 22 kJ.mol-1 and DeltaS degrees
      = -296 +/- 75 J.mol-1.K-1. For meat, riboflavin is concluded to be a
      photosensitizer for protein oxidation but not for discoloration.

PMID- 24456531
TI  - Evaluation of accuracy of casts of multiple internal connection implant
      prosthesis obtained from different impression materials and techniques: an in
      vitro study.
AB  - Movement of impression copings inside the impression material using a direct
      (open tray) impression technique during clinical and laboratory phases may cause
      inaccuracy in transferring the 3-dimensional spatial orientation of implants
      intraorally to the cast. Consequently, the prosthesis may require corrective
      procedures. This in vitro study evaluated the accuracy of 3 different impression
      techniques using polyether and vinyl polysiloxane (VPS) impression material to
      obtain a precise cast for multiple internal connection implants. A reference
      acrylic resin model with 4 internal connection implants was fabricated.
      Impressions of the reference model were made using 3 different techniques and 2
      different impression materials. The study consisted of 24 specimens divided into
      6 groups of 4 each. Impressions were poured with ADA type IV stone (Kalrock,
      Kalabhai Karson Pvt Ltd, Mumbai, India). All casts were evaluated for the
      positional accuracy (mm) of the implant replica heads using a profile projector.
      These measurements were compared to the measurements calculated on the reference
      resin model, which served as a control. Data were analyzed with 2-way analysis of
      variance (ANOVA) followed by Bonferroni multiple comparison procedures to
      evaluate group means. The results revealed significant difference for anterior
      implant distance between the 2 impression materials (P < .01) and also among the
      3 different techniques (P < .05). The lowest mean variation was found with the
      polyether impression material and the splinted technique. For posterior implants,
      the results suggested no significant difference between the 2 impression
      materials (P >= .05). Although results were not statistically significant, the
      polyether impression material showed the lowest mean variation as compared to the
      VPS impression material. However, there was a significant difference among the 3
      different techniques (P < .05). Among the 3 different techniques, the lowest mean
      variation between 2 posterior implants was found in the splinted technique. Casts
      obtained from impression techniques using square impression copings splinted
      together with autopolymerizing acrylic resin prior to the impression procedure
      were more accurate than casts obtained from impressions with nonmodified implant
      impression copings and with airborne particle-abraded, adhesive-coated copings.
      Casts obtained from polyether impression material were more accurate than casts
      obtained from vinyl polysiloxane impression material. 

PMID- 24456532
TI  - "It's easier in pharmacy": why some patients prefer to pay for flu jabs rather
      than use the National Health Service.
AB  - BACKGROUND: There is a need to increase flu vaccination rates in England
      particularly among those under 65 years of age and at risk because of other
      conditions and treatments. Patients in at risk groups are eligible for free
      vaccination on the National Health Service (NHS) in England, but despite this,
      some choose to pay privately. This paper explores how prevalent this is and why
      people choose to do it. There is moderate to good evidence from several countries
      that community pharmacies can safely provide a range of vaccinations, largely
      seasonal influenza Immunisation. Pharmacy-based services can extend the reach of
      immunisation programmes. User, doctor and pharmacist satisfaction with these
      services is high. METHOD: Data were collected during the 2012-13 flu season as
      part of a community pharmacy private flu vaccination service to help identify
      whether patients were eligible to have their vaccination free of charge on the
      NHS. Additional data were collected from a sample of patients accessing the
      private service within 13 pharmacies to help identify the reasons patients paid
      when they were eligible for free vaccination. RESULTS: Data were captured from
      89,011 privately paying patients across 479 pharmacies in England, of whom 6%
      were eligible to get the vaccination free. 921 patients completed a survey in the
      13 pharmacies selected. Of these, 199 (22%) were eligible to get their flu
      vaccination for free. 131 (66%) were female. Average age was 54 years. Of the 199
      patients who were eligible for free treatment, 100 (50%) had been contacted by
      their GP surgery to go for their vaccination, but had chosen not to go. Reasons
      given include accessibility, convenience and preference for pharmacy environment.
      CONCLUSIONS: While people at risk can access flu vaccinations free via the NHS,
      some choose to pay privately because they perceive that community pharmacy access
      is easier. There are opportunities for pharmacy to support the NHS in delivering
      free flu vaccinations to patients at risk by targeting people unlikely to access
      the service at GP surgeries.

PMID- 24456533
TI  - FLOURY ENDOSPERM6 encodes a CBM48 domain-containing protein involved in compound
      granule formation and starch synthesis in rice endosperm.
AB  - Starch is the most widespread form of energy storage in the plant kingdom.
      Although many enzymes and related factors have been identified for starch
      biosynthesis, unknown players remain to be identified, given that it is a
      complicated and sophisticated process. The endosperm of rice (Oryza sativa) has
      been used for the study of starch synthesis. Here, we report the cloning and
      characterization of the FLOURY ENDOSPERM6 (FLO6) gene in rice. In the flo6
      mutant, the starch content is decreased and the normal physicochemical features
      of starch are changed. Significantly, flo6 mutant endosperm cells show obvious
      defects in compound granule formation. Map-based cloning showed that FLO6 encodes
      a protein of unknown function. It harbors an N-terminal transit peptide that
      ensures its correct localization and functions in the plastid, and a C-terminal
      carbohydrate-binding module 48 (CBM48) domain that binds to starch. Furthermore,
      FLO6 can interact with isoamylase1 (ISA1) both in vitro and in vivo, whereas ISA1
      does not bind to starch directly. We thus propose that FLO6 may act as a starch
      binding protein involved in starch synthesis and compound granule formation
      through a direct interaction with ISA1 in developing rice seeds. Our data provide
      a novel insight into the role of proteins with the CBM48 domain in plant species.

PMID- 24456534
TI  - Acyclovir Lauriad((r)): a muco-adhesive buccal tablet for the treatment of
      recurrent herpes labialis.
AB  - The treatment of recurrent herpes labialis remains a challenge in the 21st
      century. The virus is ubiquitous and there is no vaccine against the disease.
      Although recurrence episodes are usually of shorter duration than the primary
      episode, they are debilitating to patients and there is significant stigma
      associated with the disease. Acyclovir Lauriad((r)) is a new topical agent that
      was approved by the US FDA in 2013 for the treatment of recurrent herpes
      labialis, which affects approximately 20-40% of the population worldwide. The
      drug is a muco-adhesive tablet, applied to the upper gum at the onset of
      prodromal symptoms. Utilizing Lauriad((r)) technology, a biologically active
      compound traverses the mucous membrane to deliver a high concentration of
      acyclovir directly to the site of the herpes simplex virus infection. Data from a
      Phase III clinical trial shows that this may be a promising therapy for patients
      with recurrent herpes labialis. 

PMID- 24456535
TI  - Risk of cardiovascular events in survivors of severe sepsis.
AB  - RATIONALE: The risk of cardiovascular events after severe sepsis is not known,
      and these events may explain increased long-term mortality in survivors of severe
      sepsis. OBJECTIVES: To determine whether survivors of severe sepsis
      hospitalization have high long-term risk of cardiovascular events. We examined
      whether higher risk is due to severe sepsis hospitalization or poor
      prehospitalization health status, and if the higher risk is also observed in
      patients hospitalized for infectious and noninfectious reasons, and in other
      critically ill patients. METHODS: Unmatched and matched-cohort analyses of
      Medicare beneficiaries. For unmatched analysis, we compared patients with severe
      sepsis admitted to the intensive care unit (ICU) and survived hospitalization (n
      = 4,179) to unmatched population control subjects (n = 819,283). For matched
      analysis, we propensity-score-matched each patient with severe sepsis to four
      control subjects (population, hospitalized, non-severe sepsis ICU control
      subjects, and infection hospitalization). Primary outcome was 1-year incidence
      rate of hospitalization for cardiovascular events. MEASUREMENTS AND MAIN RESULTS:
      Cardiovascular events were common among patients discharged alive after severe
      sepsis hospitalization (29.5%; 498.2 events/1,000 person-years). Survivors of
      severe sepsis had a 13-fold higher risk of cardiovascular events compared with
      unmatched control subjects (498.2 vs. 36 events/1,000 person-years; P < 0.0001),
      and a 1.9-fold higher risk compared with matched-population control subjects (P <
      0.0001). Survivors of severe sepsis had 1.1-fold higher risk compared with
      matched hospitalized patients and infection hospitalizations (P = 0.002 and
      0.001) and similar risk compared with matched-ICU control subjects. CONCLUSIONS:
      Survivors of severe sepsis have high risk of cardiovascular events. The higher
      risk is mainly due to poor prehospitalization health status, and is also seen in
      a broader population of acutely ill patients.

PMID- 24456536
TI  - Predictive factors for complications in children with esophageal atresia and
      tracheoesophageal fistula.
AB  - The objective of this study was to describe the incidence of complications in
      children with esophageal atresia (EA) with or without tracheoesophageal fistula
      (TEF) at a tertiary pediatric hospital and to identify predictive factors for
      their occurrence. A retrospective chart review of 110 patients born in or
      transferred to Sydney Children's Hospital with EA/TEF between January 1999 and
      December 2010 was done. Univariate and multivariate regression analyses were
      performed to identify predictive factors for the occurrence of complications in
      these children. From univariate analysis, early esophageal stricture formation
      was more likely in children with 'long-gap' EA (odds ratio [OR] = 16.32).
      Patients with early strictures were more likely to develop chest infections (OR =
      3.33). Patients with severe tracheomalacia were more likely to experience
      'cyanotic/dying' (OR = 180) and undergo aortopexy (OR = 549). Patients who had
      gastroesophageal reflux disease were significantly more likely to require
      fundoplication (OR = 10.83) and undergo aortopexy (OR = 6.417). From multivariate
      analysis, 'long-gap' EA was a significant predictive factor for late esophageal
      stricture formation (P = 0.007) and for gastrostomy insertion (P = 0.001). Reflux
      was a significant predictive factor for requiring fundoplication (P = 0.007) and
      gastrostomy (P = 0.002). Gastrostomy insertion (P = 0.000) was a significant
      predictive factor for undergoing fundoplication. Having a prior fundoplication (P
      = 0.001) was a significant predictive factor for undergoing a subsequent
      aortopexy. Predictive factors for the occurrence of complications post EA/TEF
      repair were identified in this large single centre pediatric study. 

PMID- 24456537
TI  - Frequency of IFNgamma-producing T cells correlates with seroreactivity and
      activated T cells during canine Trypanosoma cruzi infection.
AB  - Vaccines to prevent Trypanosoma cruzi infection in humans or animals are not
      available, and in many settings, dogs are an important source of domestic
      infection for the insect vector. Identification of infected canines is crucial
      for evaluating peridomestic transmission dynamics and parasite control
      strategies. As immune control of T. cruzi infection is dependent on humoral and
      cell-mediated immune responses, we aimed to define a serodiagnostic assay and T
      cell phenotypic markers for identifying infected dogs and studying the canine T.
      cruzi-specific immune response. Plasma samples and peripheral blood mononuclear
      cells (PBMCs) were obtained from forty-two dogs living in a T. cruzi-endemic
      region. Twenty dogs were known to be seropositive and nine seronegative by
      conventional serologic tests two years prior to our study. To determine canine
      seroreactivity, we tested sera or plasma samples in a multiplex bead array
      against eleven recombinant T. cruzi proteins. Ninety-four percent (17/18) of dogs
      positive by multiplex serology were initially positive by conventional serology.
      The frequency of IFNgamma-producing cells in PBMCs responding to T. cruzi
      correlated to serological status, identifying 95% of multiplex seropositive dogs.
      Intracellular staining identified CD4+ and CD8+ T cell populations as the sources
      of T. cruzi lysate-induced IFNgamma. Low expression of CCR7 and CD62L on CD4+ and
      CD8+ T cells suggested a predominance of effector/effector memory T cells in
      seropositive canines. These results are the first, to our knowledge, to correlate
      T. cruzi-specific antibody responses with T cell responses in naturally infected
      dogs and validate these methods for identifying dogs exposed to T. cruzi. 

PMID- 24456539
TI  - A spatial modeling framework to evaluate domestic biofuel-induced potential land
      use changes and emissions.
AB  - We present a novel bottom-up approach to estimate biofuel-induced land-use change
      (LUC) and resulting CO2 emissions in the U.S. from 2010 to 2022, based on a
      consistent methodology across four essential components: land availability, land
      suitability, LUC decision-making, and induced CO2 emissions. Using high
      resolution geospatial data and modeling, we construct probabilistic assessments
      of county-, state-, and national-level LUC and emissions for macroeconomic
      scenarios. We use the Cropland Data Layer and the Protected Areas Database to
      characterize availability of land for biofuel crop cultivation, and the CERES
      Maize and BioCro biophysical crop growth models to estimate the suitability
      (yield potential) of available lands for biofuel crops. For LUC decision-making,
      we use a county-level stochastic partial-equilibrium modeling framework and
      consider five scenarios involving annual ethanol production scaling to 15, 22,
      and 29 BG, respectively, in 2022, with corn providing feedstock for the first 15
      BG and the remainder coming from one of two dedicated energy crops. Finally, we
      derive high-resolution above-ground carbon factors from the National Biomass and
      Carbon Data set to estimate emissions from each LUC pathway. Based on these
      inputs, we obtain estimates for average total LUC emissions of 6.1, 2.2, 1.0,
      2.2, and 2.4 gCO2e/MJ for Corn-15 Billion gallons (BG), Miscanthus * giganteus
      (MxG)-7 BG, Switchgrass (SG)-7 BG, MxG-14 BG, and SG-14 BG scenarios,
      respectively.

PMID- 24456538
TI  - Public interest in medical research participation: differences by volunteer
      status and study type.
AB  - PURPOSE: We assessed national levels of public interest in medical research
      participation (MRP) and factors associated with interest as a healthy volunteer;
      as a diagnosed volunteer; and in seven study types. METHOD: Cross-sectional, Web
      based survey of the US population in June 2012. Descriptive statistics estimated
      interest in MRP and multivariable logistic regression determined associations
      between respondent-level predictors and interest in MRP. RESULTS: Of 2,668
      respondents (response rate = 61%), 41% were interested in MRP as healthy
      volunteers and 60% as diagnosed volunteers. Respondents with some college (OR =
      1.54, 1.09-2.19) or higher education (OR = 1.86, 1.29-2.70) had higher adjusted
      odds of interest as healthy volunteers. Non-Hispanic black race (OR = 0.56, 0.37
      0.86) and education below high school (OR = 0.57, 0.35-0.92) were associated with
      lower adjusted odds of interest as diagnosed volunteers. Non-Hispanic black race
      was associated with lower odds of interest in medication trials as diagnosed
      volunteers (OR = 0.61, 0.40-0.93). CONCLUSIONS: We found high levels of interest
      in MRP that contrast with low levels of prior research participation. Interest is
      higher in medical research involving noninvasive designs. Comparatively lower
      levels of interest in MRP among non-Hispanic blacks and those with less education
      raise concerns about disparities in future study enrollment.

PMID- 24456540
TI  - Endometrial carcinoma in a 15-year-old obese patient with persistent uterine
      bleeding.
AB  - Endometrial carcinoma is the most common malignancy of the upper female genital
      tract but is rare in teenagers. Here, we report the case of a 15-year-old,
      nulliparous, morbidly obese female with complaints of asthenia and
      menometrorrhagia lasting for six months. On examination, the patient had an
      enlarged uterus approximately 14 gestational weeks in size, and ultrasound
      revealed an intrauterine mass and polycystic ovaries. An endometrial biopsy
      performed during hysteroscopy revealed endometrioid adenocarcinoma, and magnetic
      resonance imaging showed myometrial invasion. The patient underwent a laparotomy
      involving total abdominal hysterectomy, right salpingo-oophorectomy, wedge-shape
      dissection of the left ovary, and pelvic and para-aortic lymphadenectomy. We
      analyze the pathogenesis of endometrial carcinoma in this case and discuss the
      risk factors for endometrial carcinoma, especially in young women. Gynecologists
      should be vigilant for persistent abnormal uterine bleeding and other signs of
      endometrial carcinoma in young women, especially those who have risk factors for
      the disease.

PMID- 24456541
TI  - Gonadal hormone levels and platelet tryptophan and serotonin concentrations in
      perimenopausal women with or without depressive symptoms.
AB  - INTRODUCTION: The etiology of depressive symptoms associated with the transition
      to menopause is still unknown; hormonal changes, serotonergic system or insomnia,
      could be a trigger to depressive symptomatology. The aim of the present study was
      to evaluate gonadal hormonal levels, platelet serotonin concentrations and
      platelet tryptophan concentrations in a group of depressed perimenopausal women
      and their healthy counterparts. METHODS: A total of 63 perimenopausal women
      between 45 and 55 years old were evaluated; of these, 44 were depressed patients,
      and 19 were perimenopausal women without depression. The instruments that were
      applied included the Center for Epidemiologic Studies Depression Scale (CES-D),
      the Hamilton Depression Rating Scale (HDRS) and the Green Climacteric Scale
      (GCS); gonadal hormone levels and platelet tryptophan and serotonin
      concentrations were measured in all participants. Differences in hormonal levels
      and tryptophan and serotonin concentrations were evaluated with respect to
      specific symptoms, such as insomnia, hot flashes, nervousness, depressed mood and
      loss of interest. RESULTS: No differences between groups were observed with
      respect to hormonal levels and tryptophan and serotonin concentrations; mean
      sleep hours and insomnia were significantly correlated with platelet tryptophan
      concentrations. CONCLUSIONS: In this sample, all symptoms of depression could not
      be explained by platelet tryptophan and serotonin concentrations and hormonal
      levels; differences were observed only when we evaluated insomnia and hot
      flashes.

PMID- 24456542
TI  - Role of ultrasonographic markers of ovarian reserve in prediction of IVF and ICSI
      outcome.
AB  - The aim of the study was to assess correlation of ultrasonographic markers of
      ovarian reserve and IVF/ICSI outcome. Two-hundred twelve IVF/ICSI patients were
      included. Upon pituitary suppression confirmation, antral follicle count (AFC),
      ovarian volume (OV), and ovarian stromal indices [vascularization index (VI),
      flow index (FI), and vascularization flow index (VFI)] were assessed by three
      dimensional (3D) and power Doppler (PD) ultrasound and correlated with the number
      of mature oocytes retrieved. The number of mature oocytes retrieved correlated
      strongly with AFC (r = 0.832, p <= 0.001) and OV (r = 0.835, p <= 0.001), but
      weakly with VI (r = 0.166, p = 0.016), FI (r = 0.151, p = 0.028), and VFI (r =
      0.14, p = 0.041). AFC and OV correlate strongly with the number of mature oocytes
      retrieved in IVF/ICSI cycles, whereas 3D PD indices of the ovarian stromal
      vascularity have a weak correlation.

PMID- 24456543
TI  - Job-related burnout and the relationship to quality of life among Chinese medical
      college staff.
AB  - Although staffs in medical colleges have traditionally been characterized as a
      stressed group of people, there are no specific studies assessing burnout and the
      relationship to quality of life (QOL). The purpose of this cross-sectional study
      was to evaluate job-related burnout and the relationship to QOL among medical
      college staff in mainland China. Some 360 medical college staffs from 15 schools
      and departments were enrolled in the study. The Chinese Teachers' Burnout
      Inventory (TBI) and the World Health Organization Quality of Life--brief Chinese
      version were used. Data on sociodemographic, work-related, and health-related
      factors were also collected. Multiple stepwise regression analysis was used to
      identify significant factors related to the 3 domain scores of the TBI.
      Structural equation modeling was performed to test the correlation between job
      related burnout and QOL. The most significant and common predictors of burnout
      prevention were a love of the teaching profession and work acknowledgment from a
      direct supervisor. Job-related burnout had a direct negative effect on QOL.
      Corresponding health policies and suggestions could be developed to prevent job
      related burnout and improve QOL.

PMID- 24456545
TI  - Comment on Sridharan V et al., 'effects of radiation on the epidermal growth
      factor receptor pathway in the heart'.

PMID- 24456544
TI  - Women's perception of quality of maternity services: a longitudinal survey in
      Nepal.
AB  - BACKGROUND: In the context of maternity service, the mother's assessment of
      quality is central because emotional, cultural and respectful supports are vital
      during labour and the delivery process. This study compared client-perceived
      quality of maternity services between birth centres, public and private hospitals
      in a central hills district of Nepal. METHODS: A cohort of 701 pregnant women of
      5 months or more gestational age were recruited and interviewed, followed by
      another interview within 45 days of delivery. Perception of quality was measured
      by a 20-item scale with three sub-scales: health facility, health care delivery,
      and interpersonal aspects. Perceived quality scores were analysed by ANOVA with
      post-hoc comparisons and multiple linear regression. RESULTS: Within the health
      facility sub-scale, birth centre was rated lowest on items 'adequacy of medical
      equipment', 'health staff suited to women's health' and 'adequacy of health
      staff', whereas public hospital was rated the lowest with respect to 'adequacy of
      room', 'adequacy of water', 'environment clean', 'privacy' and 'adequacy of
      information'. Mean scores of total quality and sub-scales health facility and
      health care delivery for women attending private hospital were higher (p < 0.001)
      than those using birth centre or public hospital. Mean score of the sub-scale
      interpersonal aspects for public hospital users was lower (p < 0.001) than those
      delivered at private hospital and birth centre. However, perception on
      interpersonal aspects by women using public hospital improved significantly after
      delivery (p < 0.001). CONCLUSIONS: Overall, perception of quality differed
      significantly by types of health facility used for delivery. They rated lowest
      the supplies and equipment in birth centres and the amenities and interpersonal
      aspects in the public hospital. Accordingly, attention to these aspects is needed
      to improve the quality.

PMID- 24456546
TI  - Actinide handling after wound entry with local or systemic decorporation therapy
      in the rat.
AB  - BACKGROUND: Treatment of actinide-contaminated wounds may be problematic because
      of contaminant physicochemical properties, dissemination and anatomical
      localization. This study investigates different chelation/resection protocols
      after contamination of rats with americium (Am) or plutonium (Pu) nitrate or
      mixed oxide (MOX; uranium (U), Pu oxide). METHODS: Anesthetized rats were
      contaminated with Am or Pu nitrate (moderately soluble) or MOX (insoluble)
      following wounding of hind leg muscle. DTPA (diethylene triamine pentaacetic
      acid) treatment (30 MUmol/kg) was immediate or delayed, systemic or local and
      combined or not with wound resection. Actinide urinary and tissue levels were
      measured. RESULTS: Comparison of Pu nitrate and MOX dissemination at the wound
      site indicated a more heterogeneous localization of MOX particles. In all cases
      DTPA treatment reduced target tissue (bone, liver) activity levels even if DTPA
      treatment was started 7 days after contamination. Surgery alone increased urinary
      excretion suggesting release from the wound site but no subsequent increases in
      organ retention (bone, liver) were observed. The combination of surgery and DTPA
      increased Pu excretion and reduced tissue levels markedly. CONCLUSION: This
      rodent model of actinide wound contamination has been used to test different
      treatments. It provides evidence of activity release as a result of surgery that
      seems not to lead to increased organ retention.

PMID- 24456547
TI  - Ionizing radiation activates PERK/eIF2alpha/ATF4 signaling via ER stress
      independent pathway in human vascular endothelial cells.
AB  - PURPOSE: Perturbations in protein folding induce endoplasmic reticulum (ER)
      stress, which elicits coordinated response, namely the unfolded protein response
      (UPR), to cope with the accumulation of misfolded proteins in ER. In this study,
      we characterized mechanisms underlying ionizing radiation (IR)-induced UPR
      signaling pathways. MATERIALS AND METHODS: We analyzed alterations in UPR
      signaling pathways in human umbilical vein endothelial cells (HUVEC) and human
      coronary artery endothelial cells (HCAEC) irradiated with 15 Gy IR. RESULTS: IR
      selectively activated the eIF2alpha/ATF4 branch of the UPR signaling pathway,
      with no alterations in the IRE1 and ATF6 branches in HUVEC and HCAEC.
      Phosphorylation of PERK was enhanced in response to IR, and the IR-induced
      activation of the eIF2alpha/ATF4 signaling pathway was completely inhibited by
      PERK knockdown with siRNA. Surprisingly, chemical chaperones, which inhibit the
      formation of misfolded proteins and sequential protein aggregates to reduce ER
      stress, failed to prevent the IR-induced phosphorylation of PERK and the
      subsequent activation of the eIF2alpha/ATF4 signaling pathway. CONCLUSIONS: PERK
      mediates the IR-induced selective activation of the eIF2alpha/ATF4 signaling
      pathway, and the IR-induced activation of PERK/eIF2alpha/ATF4 signaling in human
      vascular endothelial cells is independent of alterations in protein-folding
      homeostasis in the ER.

PMID- 24456548
TI  - Deployment and PTSD in the female combat veteran: a systematic review.
AB  - BACKGROUND: The number of females serving in the Gulf War has risen and continues
      to be a rapidly growing group. Females occupy a wide range of roles and face a
      myriad of challenges as they serve alongside their male counterparts in almost
      every role. Females are also facing redeployment, multiple deployments, and/or
      extended deployments. The stressors of war and deployments may be putting them at
      risk for posttraumatic stress disorder (PTSD). If left untreated, PTSD can have
      devastating and debilitating consequences for veteran's functioning and
      relationships, their families, and society. OBJECTIVE: To examine the literature
      over the past 10 years to determine if there is a relationship between
      deployments and the incidence of PTSD in female combat veterans as compared with
      male veterans. METHOD: Systematic review. RESULTS: The numbers of veterans
      screening for PTSD are increasing. Those who have experienced extended or
      multiple tours have higher screening rates. Females report slightly less combat
      exposure than males but higher exposures to other stressors of war such as
      military sexual trauma. Females were at higher risk for depression while males
      were at higher risk of substance abuse. Females and lower rank were associated
      with greater utilization of Veterans Administration services.

PMID- 24456549
TI  - Risk: a multidisciplinary concept analysis.
AB  - PURPOSE: To analyze the concept of risk utilizing Walker and Avant's method of
      analysis to determine a conceptual definition applicable within nursing and
      nursing research. CONCLUSION: The mental constructs and consequences of risk have
      a proactive connotation compared with the negative behaviors often identified as
      illustrations of risk. PRACTICE APPLICATION: A new conceptual definition of risk
      provides insight into an understanding of risk regardless of discipline. Its
      application to the metaparadigm of nursing should be the impetus for action and
      education. Formalizing the mental constructs of the concept of risk in a clear
      manner facilitates the inclusion of its latent constructs in nursing research.

PMID- 24456550
TI  - Health coaching: a concept analysis.
AB  - PURPOSE: Variations in the use of health coaching documented in the literature
      indicate a lack of conceptual clarity. The purpose of this article was to clarify
      the meaning of health coaching and propose an operational definition.
      CONCLUSIONS: Seven attributes were identified and used to propose an operational
      definition of health coaching as a goal-oriented, client-centered partnership
      that is health-focused and occurs through a process of client enlightenment and
      empowerment. PRACTICE IMPLICATION: This operational definition and the proposed
      empirical measures of each attribute can be used to validate the presence of
      health coaching, develop theory-based applications, and consistently test the
      effectiveness of interventions using this concept.

PMID- 24456551
TI  - A nurse-led wellness program for migrant backstretch workers.
AB  - PROBLEM: Migrant workers working at the back stretch of Philadelphia Park
      Racetrack are faced with healthcare challenges. This vulnerable population
      experiences health disparities as a result of lack of resources and increased
      exposure to risk. METHOD: A needs assessment of backstretch workers was conducted
      to identify the healthcare needs of this unique population. FINDINGS: The
      analysis revealed several areas of need for this vulnerable population primarily,
      effective bilingual communication, increasing access to healthcare services,
      implementing measures to address women's health issues, and improving nutritional
      status of workers. CONCLUSION: Through multi-agency collaboration, continued
      development, and revision of strategies, health enhancement and disease
      prevention are accessible to vulnerable migrant workers. Faculty, students, and
      staff work with clients to provide quality health education programs, screenings,
      and referrals to improve their health.

PMID- 24456552
TI  - An exploration of the concept of connect.
AB  - AIM: The purpose is to explore the concept of connect in multiple disciplines for
      further development of knowledge and theories in nursing and to establish a clear
      understanding of this construct. BACKGROUND: Connect has meanings rooted in the
      discipline of business, technology, and transportation which influence how the
      term is defined in nursing. Several definitions have been established that
      demonstrate the concepts of connect in other disciplines. DESIGN: A concept
      exploration design was used for the identification and explication of the term
      connect to describe, explain, and predict this interprofessional phenomenon.
      REVIEW METHODS: The databases CINAHL, MEDLINE, PRO-Quest, and EBSCO were searched
      for articles through title and abstract screening using connect, connectedness,
      and connectivity. RESULTS: Three specific components were identified in the
      exploration: (a) respect, (b) trust, and (c) mutuality. Current literature
      validated the need for an empirical concept analysis. CONCLUSIONS: This concept
      exploration provides the first step in understanding the context and meaning of
      connect in nursing profession. By determining if connections exist and
      quantifying the level of connections, a level of congruency between the nurse and
      the patient can be established to determine the best plan of care and goals. An
      empirical measure of connect will benefit nursing and other disciplines.

PMID- 24456553
TI  - Eating, activity, and supportive environment (EASE) for nursing students.
AB  - PURPOSE: The feasibility study was designed as a potential model for prevention
      of obesity at a large college of nursing in the Southwest. CONCLUSIONS: Pretest
      median body mass index was 30.4 in the intervention group and 30.5 in the control
      group, indicating obesity in the student sample. There were no significant
      changes in posttest measures in the small sample. The thigh circumference change
      in the experimental group trended toward change with significance of .06.
      IMPLICATION: The American Nursing Association launched a Healthy Nurse program in
      2012, as healthy nurses are role models for a healthy nation. Updating nursing
      curriculum and active participation of students in weight management programs
      will promote their own health and positive role modeling.

PMID- 24456554
TI  - A review of potential Muslim organ donors' perspectives on solid organ donation:
      lessons for nurses in clinical practice.
AB  - BACKGROUND: Transplantation is increasingly being used to treat patients with end
      stage organ disease. However, when potential organ donors involved are Muslims,
      religious beliefs and culture have a strong influence on clinical decision making
      and nursing care. PURPOSE: To establish basic aspects that nurses working with
      potential Muslim organ donors need to know in order to provide culturally
      sensitive care. METHODS: Studies were retrieved from four databases (Cumulative
      Index to Nursing and Allied Health Literature, SCOPUS, Medline, and PubMed).
      RESULTS: Findings of available studies show that health education, family
      involvement, and collaboration with religious leaders are good strategies for
      ensuring culturally sensitive care for Muslim patients in this situation.
      CONCLUSION: Nurses need to know that organ donation is compatible with Islam and
      that religious leaders, family, sociocultural beliefs, legal requirements,
      informed decision making process, and Ramadan are important aspects that need to
      be considered in order to be able to provide culturally senstive care.

PMID- 24456555
TI  - Stress: a concept analysis.
AB  - PURPOSE: To analyze the concept of stress and provide an operational definition
      of stress. CONCLUSIONS: Literature review revealed that stress is a commonly
      used, but often ambiguous, term. Findings supported a definition of stress
      entailing an individual's perception of a stimulus as overwhelming, which in turn
      elicits a measurable response resulting in a transformed state. PRACTICE
      IMPLICATIONS: This analysis adopts a dynamic definition of stress that may serve
      to encourage communication, promote reflection, and enhance concept
      understanding. This definition may provide direction for future work, as well as
      enhance efforts to serve patients affected by stress.

PMID- 24456556
TI  - Stilbenes as kappa-selective, non-nitrogenous opioid receptor antagonists.
AB  - The natural stilbene pawhuskin A has been shown to function as an opioid receptor
      antagonist, with preferential binding to the kappa receptor. This finding
      encouraged assembly of a set of analogues to probe the importance of key
      structural features. Assays on these compounds determined that one (compound 29)
      shows potent opioid receptor binding activity and significantly improved
      selectivity for the kappa receptor. These studies begin to illuminate the
      structural features of these non-nitrogenous opioid receptor antagonists that are
      required for activity. 

PMID- 24456557
TI  - Single-source magnetic nanorattles by using convenient emulsion polymerization
      protocols.
AB  - A novel strategy to achieve easily scalable magneto-responsive nanoceramics with
      core/shell and nanorattle-type or yolk/shell architectures based on a ferrocene
      containing polymer precursor is described. Monodisperse nanorattle-type magnetic
      particles are obtained by using convenient semicontinuous emulsion polymerization
      and Stober process protocols followed by thermal treatment. The particles are
      characterized by TGA, TEM, WAXS, DLS, XPS, and Raman spectroscopy. Herein,
      established synthetic protocols widen opportunities for the convenient bottom-up
      strategies of various ferrocene-precursor-based spherical architectures for
      advanced ceramics with potential applications within fields of sensing and
      stimuli-responsive nanophotonics. 

PMID- 24456558
TI  - Multiple actinic keratosis, squamous cell carcinoma and basal cell carcinoma
      occurred after PUVA therapy in a Korean patient.

PMID- 24456559
TI  - DsbM affects aminoglycoside resistance in Pseudomonas aeruginosa by the reduction
      of OxyR.
AB  - DsbM is a novel disulfide oxidoreductase that affects aminoglycoside resistance
      in Pseudomonas aeruginosa by an OxyR-regulated process. However, the detailed
      mechanism of interaction between DsbM and OxyR had not yet been elucidated. In
      this study, we expressed DsbM in Escherichia coli and showed that DsbM can
      oxidize and reduce disulfide. We also used a yeast two-hybrid assay to identify
      interactions between DsbM and OxyR. A subsequent GSH oxidation experiment
      revealed that DsbM could alter both the oxidized and reduced state of OxyR. We
      hypothesized that OxyR can be reduced by DsbM, and thus DsbM may be required for
      aminoglycoside resistance in P. aeruginosa. Our findings contribute to the
      understanding of the mechanisms underlying aminoglycoside resistance in P.
      aeruginosa.

PMID- 24456560
TI  - Decreased oxygen extraction during cardiopulmonary exercise test in patients with
      chronic fatigue syndrome.
AB  - BACKGROUND: The insufficient metabolic adaptation to exercise in Chronic Fatigue
      Syndrome (CFS) is still being debated and poorly understood. METHODS: We analysed
      the cardiopulmonary exercise tests of CFS patients, idiopathic chronic fatigue
      (CFI) patients and healthy visitors. Continuous non-invasive measurement of the
      cardiac output by Nexfin (BMEYE B.V. Amsterdam, the Netherlands) was added to the
      cardiopulmonary exercise tests. The peak oxygen extraction by muscle cells and
      the increase of cardiac output relative to the increase of oxygen uptake
      (DeltaQ'/DeltaV'O2) were measured, calculated from the cardiac output and the
      oxygen uptake during incremental exercise. RESULTS: The peak oxygen extraction by
      muscle cells was 10.83 +/- 2.80 ml/100ml in 178 CFS women, 11.62 +/- 2.90 ml/100
      ml in 172 CFI, and 13.45 +/- 2.72 ml/100 ml in 11 healthy women (ANOVA: P=0.001),
      13.66 +/- 3.31 ml/100 ml in 25 CFS men, 14.63 +/- 4.38 ml/100 ml in 51 CFI, and
      19.52 +/- 6.53 ml/100 ml in 7 healthy men (ANOVA: P=0.008).The DeltaQ'/DeltaV'O2
      was > 6 L/L (normal DeltaQ'/DeltaV'O2 ~ 5 L/L) in 70% of the patients and in 22%
      of the healthy group. CONCLUSION: Low oxygen uptake by muscle cells causes
      exercise intolerance in a majority of CFS patients, indicating insufficient
      metabolic adaptation to incremental exercise. The high increase of the cardiac
      output relative to the increase of oxygen uptake argues against deconditioning as
      a cause for physical impairment in these patients.

PMID- 24456561
TI  - Reducing hospital admissions from nursing homes: a systematic review.
AB  - BACKGROUND: The geriatric nursing home population is vulnerable to acute and
      deteriorating illness due to advanced age, multiple chronic illnesses and high
      levels of dependency. Although the detriments of hospitalising the frail and old
      are widely recognised, hospital admissions from nursing homes remain common.
      Little is known about what alternatives exist to prevent and reduce hospital
      admissions from this setting. The objective of this study, therefore, is to
      summarise the effects of interventions to reduce acute hospitalisations from
      nursing homes. METHODS: A systematic literature search was performed in Cochrane
      Library, PubMed, MEDLINE, EMBASE and ISI Web of Science in April 2013. Studies
      were eligible if they had a geriatric nursing home study population and were
      evaluating any type of intervention aiming at reducing acute hospital admission.
      Systematic reviews, randomised controlled trials, quasi randomised controlled
      trials, controlled before-after studies and interrupted time series were eligible
      study designs. The process of selecting studies, assessing them, extracting data
      and grading the total evidence was done by two researchers individually, with any
      disagreement solved by a third. We made use of meta-analyses from included
      systematic reviews, the remaining synthesis is descriptive. Based on the type of
      intervention, the included studies were categorised in: 1) Interventions to
      structure and standardise clinical practice, 2) Geriatric specialist services and
      3) Influenza vaccination. RESULTS: Five systematic reviews and five primary
      studies were included, evaluating a total of 11 different interventions. Fewer
      hospital admissions were found in four out of seven evaluations of structuring
      and standardising clinical practice; in both evaluations of geriatric specialist
      services, and in influenza vaccination of residents. The quality of the evidence
      for all comparisons was of low or very low quality, using the GRADE approach.
      CONCLUSIONS: Overall, eleven interventions to reduce hospital admissions from
      nursing homes were identified. None of them were tested more than once and the
      quality of the evidence was low for every comparison. Still, several
      interventions had effects on reducing hospital admissions and may represent
      important aspects of nursing home care to reduce hospital admissions.

PMID- 24456562
TI  - Prenatal ultrasonography and Doppler sonography for the clinical investigation of
      isolated ventricular septal defects in a late second-trimester population.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of prenatal
      ultrasonography and Doppler sonography in detecting isolated ventricular septal
      defects (VSDs) in a late-second-trimester population. METHODS: Fetal
      echocardiography, Doppler ultrasound, and biometry were used to evaluate 2,661
      singleton fetuses (1,381 male fetuses and 1,280 female fetuses) between 1 August
      2006 and 31 May 2010. The efficacy of each fetal biometry, Doppler ultrasound,
      and nasal bone length (NBL) measurement was evaluated in all of the fetuses. A
      standard fetal echocardiographic evaluation, including two-dimensional gray-scale
      imaging and color and Doppler color flow mapping, was performed on all fetuses.
      RESULTS: We detected isolated VSDs in 124 of the 2,661 singleton fetuses between
      19 and 24 weeks of gestation. The prevalence of isolated VSDs in the study
      population was 4.66%. A multiple logistic regression analysis indicated that
      short fetal NBL (odds ratio = 0.691, 95% confidence interval: 0.551 to 0.868) and
      the pulsatility index (PI) of the umbilical artery (odds ratio = 8.095, 95%
      confidence interval: 4.309 to 15.207) and of the middle cerebral artery (odds
      ratio = 0.254, 95% confidence interval: 0.120 to 0.538) are significantly
      associated with isolated VSDs. CONCLUSION: Late-second-trimester fetal NBL,
      umbilical artery PI, and middle cerebral artery PI are useful parameters for
      detecting isolated VSDs, and can be used to estimate the a priori risk of VSDs in
      women at high risk and at low risk of isolated VSDs.

PMID- 24456563
TI  - Allosteric modulation of GABAA receptors by extracellular ATP.
AB  - BACKGROUND: The gamma-aminobutyric acid type A receptor (GABAAR) is the primary
      receptor mediating fast synaptic inhibition in the brain and plays a critical
      role in modulation of neuronal excitability and neural networks. Previous studies
      have demonstrated that ATP and its nucleotide analogs may regulate the function
      of GABAARs via Ca2+-dependent intracellular mechanisms, which require activation
      of purinergic 2 (P2) receptors or cross-talk between two receptors. RESULTS:
      Here, we report a potentiation of GABAARs by extracellular ATP via a previously
      un-recognized allosteric mechanism. Using cultured hippocampal neurons as well as
      HEK293 cells transiently expressing GABAARs, we demonstrate that extracellular
      ATP potentiates GABAAR mediated currents in a dose-dependent manner with an EC50
      of 2.1 +/- 0.2 mM. The potentiation was mediated by a postsynaptic mechanism that
      was not dependent on activation of either ecto-protein kinase or P2 receptors.
      Single channel recordings from cell-free excised membrane patches under outside
      out mode or isolated membrane patches under cell-attached mode suggest that the
      ATP modulation of GABA currents is achieved through a direct action of ATP on the
      channels themselves and manifested by increasing the single channel open
      probability without alteration of its conductance. Moreover, this ATP
      potentiation of GABAAR could be reconstituted in HEK293 cells that transiently
      expressed recombinant rat GABAARs. CONCLUSIONS: Our data strongly suggest that
      extracellular ATP allosterically potentiates GABAAR-gated chloride channels. This
      novel mode of ATP-mediated modulation of GABAARs may play an important role in
      regulating neuronal excitability and thereby in fine-tuning the excitation
      inhibition balance under conditions where a high level of extracellular ATP is
      ensured.

PMID- 24456564
TI  - Combined pulmonary lobectomy for surgical treatment of a malignant fibrous
      histiocytoma of the chest wall: a case report.
AB  - BACKGROUND: A malignant fibrous histiocytoma (MFH) rarely originates from the
      chest wall. CLINICAL FINDINGS: In this case, we describe a 59-year-old Chinese
      woman who presented with an enormous mass originating from the left chest wall
      and involving the left upper pulmonary lobe. THERAPY: After a radical en-block
      resection of the entire chest mass with left upper pulmonary lobectomy, and the
      chest wall reconstruction, a histopathologic diagnosis of the giant cell MFH was
      rendered. She has done well postoperatively, showing no local recurrence or
      distal disease in an 8-month follow-up period. CONCLUSION: Although a MFH
      originating from the chest wall is rare, it should be considered in the
      differential diagnosis of a chest wall tumor. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/8895569301129379.

PMID- 24456565
TI  - Toward functional screening of cardioactive and cardiotoxic drugs with zebrafish
      in vivo using pseudodynamic three-dimensional imaging.
AB  - Given the high mortality in patients with cardiovascular diseases and the life
      threatening consequences of drugs with unforeseen adverse effects on hearts, a
      critical evaluation of the pharmacological response of cardiovascular function on
      model animals is important especially in the early stages of drug development. We
      report a proof-of-principle study to demonstrate the utility of zebrafish as an
      analytical platform to predict the cardiac response of new drugs or chemicals on
      human beings. With pseudodynamic 3D imaging, we derive individual parameters that
      are central to the cardiac function of zebrafish, including the ventricular
      stroke volume, ejection fraction, cardiac output, heart rate, diastolic filling
      function, and ventricular mass. We evaluate both inotropic and chronotropic
      responses of the heart of zebrafish treated with drugs that are commonly
      prescribed and possess varied known cardiac activities. We reveal deranged
      cardiac function of a zebrafish model of cardiomyopathy induced with a
      cardiotoxic drug. The cardiac function of zebrafish exhibits a pharmacological
      response similar to that of human beings. We compare also cardiac parameters
      obtained in this work with those derived with conventional 2D approximation and
      show that the latter tends to overestimate the cardiac parameters and produces
      results of greater variation. In view of the growing interest of using zebrafish
      in both fundamental and translational biomedical research, we envisage that our
      approach should benefit not only contemporary pharmaceutical development but also
      exploratory research such as gene, stem cell, or regenerative therapies targeting
      congenital or acquired heart diseases. 

PMID- 24456566
TI  - Galactose content of legumes, caseinates, and some hard cheeses: implications for
      diet treatment of classic galactosemia.
AB  - There are inconsistent reports on the lactose and/or galactose content of some
      foods traditionally restricted from the diet for classic galactosemia. Therefore,
      samples of cheeses, caseinates, and canned black, pinto, kidney, and garbanzo
      beans were analyzed for free galactose content using HPLC with refractive index
      or pulsed amperometric detection. Galactose concentrations in several hard and
      aged cheeses and three mild/medium Cheddars, produced by smaller local dairies,
      was <10 mg/100 g sample compared to 55.4 mg/100 g sample in four sharp Cheddars
      produced by a multinational producer. Galactose in sodium and calcium caseinate
      ranged from undetectable to 95.5 mg/100 g sample. Free galactose level in
      garbanzo beans was lower than previously reported at 24.6 mg/100 g sample; black
      beans contained 5.3 mg/100 g, and free galactose was not detected in red kidney
      or pinto beans. These data provide a basis for recommending inclusion of legumes,
      caseinate-containing foods, and some aged hard cheeses that had been previously
      restricted in the diet for individuals with galactosemia. 

PMID- 24456571
TI  - Assessment and Analysis of Workplace Violence in a Greek Tertiary Hospital.
AB  - This study sought to assess workplace violence in a Greek tertiary hospital for
      the first time. The authors conducted a descriptive study with 175 participants
      and examined the characteristics of violent episodes, the responses of victims
      and the administration, and the perception of workplace safety in addition to the
      implications of these incidents. The vast majority of employees (83.4%) had
      experienced work-related violence; however, half of them (52%) had not reported
      the incident to the hospital administration. Verbal violence was the most common
      type of incident (98.6%). Nurses and other health care staff reported feeling
      safer than physicians (odds ratio [OR] = 4.47, 95% confidence interval [CI]: 1.94
      10.28 and OR = 2.80, 95% CI: 1.64-8.74, respectively). A large proportion of
      victims (72.6%) suffered psychological consequences following the violent
      incident. This study reveals the high prevalence of workplace violence in a Greek
      tertiary hospital and underscores its negative impact on health care workers. 

PMID- 24456572
TI  - On the role of GAPDH isoenzymes during pentose fermentation in engineered
      Saccharomyces cerevisiae.
AB  - In the metabolic network of the cell, many intermediary products are shared
      between different pathways. d-Glyceraldehyde-3-phosphate, a glycolytic
      intermediate, is a substrate of GAPDH but is also utilized by transaldolase and
      transketolase in the scrambling reactions of the nonoxidative pentose phosphate
      pathway. Recent efforts to engineer baker's yeast strains capable of utilizing
      pentose sugars present in plant biomass rely on increasing the carbon flux
      through this pathway. However, the competition between transaldolase and GAPDH
      for d-glyceraldehyde-3-phosphate produced in the first transketolase reaction
      compromises the carbon balance of the pathway, thereby limiting the product
      yield. Guided by the hypothesis that reduction in GAPDH activity would increase
      the availability of d-glyceraldehyde-3-phosphate for transaldolase and thereby
      improve ethanol production during fermentation of pentoses, we performed a
      comprehensive characterization of the three GAPDH isoenzymes in baker's yeast,
      Tdh1, Tdh2, and Tdh3 and analyzed the effect of their deletion on xylose
      utilization by engineered strains. Our data suggest that overexpression of
      transaldolase is a more promising strategy than reduction in GAPDH activity to
      increase the flux through the nonoxidative pentose phosphate pathway. 

PMID- 24456567
TI  - The CTSA Consortium's Catalog of Assets for Translational and Clinical Health
      Research (CATCHR).
AB  - The 61 CTSA Consortium sites are home to valuable programs and infrastructure
      supporting translational science and all are charged with ensuring that such
      investments translate quickly to improved clinical care. Catalog of Assets for
      Translational and Clinical Health Research (CATCHR) is the Consortium's effort to
      collect and make available information on programs and resources to maximize
      efficiency and facilitate collaborations. By capturing information on a broad
      range of assets supporting the entire clinical and translational research
      spectrum, CATCHR aims to provide the necessary infrastructure and processes to
      establish and maintain an open-access, searchable database of consortium
      resources to support multisite clinical and translational research studies. Data
      are collected using rigorous, defined methods, with the resulting information
      made visible through an integrated, searchable Web-based tool. Additional easy-to
      use Web tools assist resource owners in validating and updating resource
      information over time. In this paper, we discuss the design and scope of the
      project, data collection methods, current results, and future plans for
      development and sustainability. With increasing pressure on research programs to
      avoid redundancy, CATCHR aims to make available information on programs and core
      facilities to maximize efficient use of resources. 

PMID- 24456573
TI  - Inter-reflux and bolus clearance times in non-pathologic pediatric patients: data
      support computational models.
AB  - Previous contributions suggested that gastroesophageal reflux can be modeled in
      terms of a Poisson process. This study aims to provide empirical data to validate
      this statement in pediatric patients so that computational models can be broadly
      used as an alternative for research. A retrospective review of 63 pediatric
      patients who underwent 24-hour impedance-pH monitoring to discard
      gastroesophageal reflux disease was conducted in this study. Patients were
      grouped by age as preterm (21), infants (21), and children (21). All the tracings
      were analyzed by a trained physician who identified the reflux entry and the
      bolus clearance time of each episode. The time between reflux episodes was tested
      against three probability distributions (gamma, exponential and inverse Gaussian)
      whereas the bolus clearance time was tested against a normal probability
      distribution. Parameters were estimated using the maximum likelihood method. The
      Kolmogorov-Smirnov test and the Kullback-Leibler divergence were computed to
      evaluate the goodness of fit. One-way analysis of variance was applied to compare
      results along the three groups. Exponential fitting for inter-reflux time was
      successful in 90.48% of children older than 1 year. The overall reflux rate was
      57.58 reflux episodes per day whereas the mean bolus clearance time ranged
      between 10.87 in preterm subjects and 12.05 in children, showing a good Gaussian
      fitting. The time between reflux episodes can be modeled in terms of a Poisson
      process in non tube-fed patients, whereas the bolus clearance time follows a
      normal distribution in all cases. 

PMID- 24456574
TI  - A genome-wide linkage analysis for reproductive traits in F2 Large White *
      Meishan cross gilts.
AB  - Female reproductive performance traits in pigs have low heritabilities thus
      limiting improvement through traditional selective breeding programmes. However,
      there is substantial genetic variation found between pig breeds with the Chinese
      Meishan being one of the most prolific pig breeds known. In this study, three
      cohorts of Large White * Meishan F2 cross-bred pigs were analysed to identify
      quantitative trait loci (QTL) with effects on reproductive traits, including
      ovulation rate, teat number, litter size, total born alive and prenatal survival.
      A total of 307 individuals were genotyped for 174 genetic markers across the
      genome. The genome-wide analysis of the trait-recorded F2 gilts in their first
      parity/litter revealed one QTL for teat number significant at the genome level
      and a total of 12 QTL, which are significant at the chromosome-wide level, for:
      litter size (three QTL), total born alive (two QTL), ovulation rate (four QTL),
      prenatal survival (one QTL) and teat number (two QTL). Further support for eight
      of these QTL is provided by results from other studies. Four of these 12 QTL were
      mapped for the first time in this study: on SSC15 for ovulation rate and on SSC18
      for teat number, ovulation rate and litter size. 

PMID- 24456575
TI  - Combined immune thrombocytopenic purpura and immunoglobulin A nephropathy: a
      similar pathophysiologic process?
AB  - IgA nephropathy is one of the most common forms of glomerulopathies. It is an
      immune complex-mediated glomerulonephritis diagnosed by the presence of mesangial
      IgA deposits that are often associated with mesangial cell proliferation. The
      IgG, C3, IgM, or other immunoglobulin light chains may be co-existed with IgA.
      Its pathogenesis suggested that it is responsible for enhancing the production of
      proinflammatory cytokines, chemokines, and growth factors. Platelet-derived
      growth factor (PDGF) has also been implicated as a modulator of disease activity.
      Immune thrombocytopenic purpura (ITP) is a bleeding disorder caused by
      thrombocytopenia that is not associated with a systemic disease. Its pathogenesis
      suggested an autoimmune disease in which IgG is thought to damage megakaryocytes,
      which are the precursors of platelet cells. Several studies reported that PDGF
      levels were higher in normal subjects than in patients with ITP. Moreover, ITP is
      a disease related to the antibody. Thus, our aim is to examine whether a similar
      pathophysiological relationship exist between ITP and IgAN that may be mediated
      by PDGF and/or IgG.

PMID- 24456576
TI  - Caseload midwifery compared to standard or private obstetric care for first time
      mothers in a public teaching hospital in Australia: a cross sectional study of
      cost and birth outcomes.
AB  - BACKGROUND: In many countries midwives act as the main providers of care for
      women throughout pregnancy, labour and birth. In our large public teaching
      hospital in Australia we restructured the way midwifery care is offered and
      introduced caseload midwifery for one third of women booked at the hospital. We
      then compared the costs and birth outcomes associated with caseload midwifery
      compared to the two existing models of care, standard hospital care and private
      obstetric care. METHODS: We undertook a cross sectional study examining the risk
      profile, birth outcomes and cost of care for women booked into one of the three
      available models of care in a tertiary teaching hospital in Australia between
      July 1st 2009 December 31st 2010. To control for differences in population or
      case mix we described the outcomes for a cohort of low risk first time mothers
      known as the 'standard primipara'. RESULTS: Amongst the 1,379 women defined as
      'standard primipara' there were significant differences in birth outcome. These
      first time 'low risk' mothers who received caseload care were more likely to have
      a spontaneous onset of labour and an unassisted vaginal birth 58.5% in MGP
      compared to 48.2% for Standard hospital care and 30.8% with Private obstetric
      care (p < 0.001). They were also significantly less likely to have an elective
      caesarean section 1.6% with MGP versus 5.3% with Standard care and 17.2% with
      private obstetric care (p < 0.001). From the public hospital perspective, over
      one financial year the average cost of care for the standard primipara in MGP was
      $3903.78 per woman. This was $1375.45 less per woman than those receiving Private
      obstetric care and $1590.91 less than Standard hospital care per woman (p <
      0.001). Similar differences in cost were found in favour of MGP for all women in
      the study who received caseload care. CONCLUSIONS: Cost reduction appears to be
      achieved through reorganising the way care is delivered in the public hospital
      system with the introduction of Midwifery Group Practice or caseload care. The
      study also highlights the unexplained clinical variation that exists between the
      three models of care in Australia.

PMID- 24456577
TI  - Fundamentals of nanoscale polymer-protein interactions and potential
      contributions to solid-state nanobioarrays.
AB  - Protein adsorption onto polymer surfaces is a very complex, ubiquitous, and
      integrated process, impacting essential areas of food processing and packaging,
      health devices, diagnostic tools, and medical products. The nature of protein
      surface interactions is becoming much more complicated with continuous efforts
      toward miniaturization, especially for the development of highly compact protein
      detection and diagnostic devices. A large body of literature reports on protein
      adsorption from the perspective of ensemble-averaged behavior on macroscopic,
      chemically homogeneous, polymeric surfaces. However, protein-surface interactions
      governing the nanoscale size regime may not be effectively inferred from their
      macroscopic and microscopic characteristics. Recently, research efforts have been
      made to produce periodically arranged, nanoscopic protein patterns on diblock
      copolymer surfaces solely through self-assembly. Intriguing protein adsorption
      phenomena are directly probed on the individual biomolecule level for a
      fundamental understanding of protein adsorption on nanoscale surfaces exhibiting
      varying degrees of chemical heterogeneity. Insight gained from protein assembly
      on diblock copolymers can be effectively used to control the surface density,
      conformation, orientation, and biofunctionality of prebound proteins in highly
      miniaturized applications, now approaching the nanoscale. This feature article
      will highlight recent experimental and theoretical advances made on these fronts
      while focusing on single-biomolecule-level investigations of protein adsorption
      behavior combined with surface chemical heterogeneity on the length scale
      commensurate with a single protein. This article will also address advantages and
      challenges of the self-assembly-driven patterning technology used to produce
      protein nanoarrays and its implications for ultrahigh density, functional, and
      quantifiable protein detection in a highly miniaturized format. 

PMID- 24456578
TI  - Isochromans and alpha-pyrones from Penicillium corylophilum.
AB  - Seven new secondary metabolites, four isochromans (1-4) and three alpha-pyrones
      (5-7), were isolated from Penicillium corylophilum DAOM 242293 collected from a
      damp building in Halifax, Canada. Their structures were elucidated by HRESIMS, 1D
      and 2D NMR, chemical derivatization, ORD, UV, and comparison to the literature.
      Related isochromans have previously been reported from other Penicillium species;
      however, to our knowledge this is the first report of alpha-pyrones from P.
      corylophilum. Compounds 1-4 demonstrated antifungal activity against
      Saccharomyces cerevisiae at 100 MUg mL(-1). 

PMID- 24456579
TI  - Response to letter: "Methadone toxicity: comparing tablet and syrup formulations
      during a decade in an academic poison center of Iran".

PMID- 24456580
TI  - Exploring factors that contribute to dose administration aid incidents and
      identifying quality improvement strategies: the views of pharmacy and nursing
      staff.
AB  - BACKGROUND: Dose administration aids (DAAs) organise medicines that have been
      repacked according to the day of the week and time of the day in which they must
      be taken. In Australia, DAAs are commonly prepared by pharmacy staff for
      residential aged care facility (RACF) medicine administration. Although the
      limited available literature indicates that DAA incidents of inaccurate or
      unsuitable medicine repacking do occur, there is a paucity of qualitative
      research identifying quality improvement strategies for this service. OBJECTIVES:
      This study aims to investigate the perceived contributing factors to DAA
      incidents and strategies for quality improvement in RACFs and pharmacies.
      METHODS: Health professional perceptions were drawn from three structured focus
      groups, including six pharmacists, five nurses, a pharmacy technician and a
      personal care worker. Participants were involved in the preparation, supply or
      use of DAAs at pharmacies or RACFs that were involved in a previous DAA audit.
      Transcripts were analysed using thematic analysis. KEY FINDINGS: Four major
      themes were identified as contributing to DAA incidents, with quality improvement
      strategies aligned to those same four themes: communication, knowledge and
      awareness, medicine handling and attitude. Strategies included improving
      interprofessional communication and addressing the limitations associated with
      RACF medicine records; targeting medicine knowledge gaps and increasing awareness
      of DAA incidents; encouraging greater care when preparing and checking DAAs; and
      fostering a team mentality among members of the aged care team. CONCLUSIONS:
      Recommendations include using current findings to develop multidisciplinary
      quality improvement initiatives to prevent DAA incidents and to improve the
      quality of this pharmacy medicine supply service.

PMID- 24456581
TI  - A comparative study: the impact of different lipid extraction methods on current
      microalgal lipid research.
AB  - Microalgae cells have the potential to rapidly accumulate lipids, such as
      triacylglycerides that contain fatty acids important for high value fatty acids
      (e.g., EPA and DHA) and/or biodiesel production. However, lipid extraction
      methods for microalgae cells are not well established, and there is currently no
      standard extraction method for the determination of the fatty acid content of
      microalgae. This has caused a few problems in microlagal biofuel research due to
      the bias derived from different extraction methods. Therefore, this study used
      several extraction methods for fatty acid analysis on marine microalga
      Tetraselmis sp. M8, aiming to assess the potential impact of different
      extractions on current microalgal lipid research. These methods included
      classical Bligh & Dyer lipid extraction, two other chemical extractions using
      different solvents and sonication, direct saponification and supercritical CO2
      extraction. Soxhlet-based extraction was used to weigh out the importance of
      solvent polarity in the algal oil extraction. Coupled with GC/MS, a
      Thermogravimetric Analyser was used to improve the quantification of microalgal
      lipid extractions. Among these extractions, significant differences were observed
      in both, extract yield and fatty acid composition. The supercritical extraction
      technique stood out most for effective extraction of microalgal lipids,
      especially for long chain unsaturated fatty acids. The results highlight the
      necessity for comparative analyses of microalgae fatty acids and careful choice
      and validation of analytical methodology in microalgal lipid research.

PMID- 24456583
TI  - A comprehensive evaluation of multicategory classification methods for
      microbiomic data.
AB  - BACKGROUND: Recent advances in next-generation DNA sequencing enable rapid high
      throughput quantitation of microbial community composition in human samples,
      opening up a new field of microbiomics. One of the promises of this field is
      linking abundances of microbial taxa to phenotypic and physiological states,
      which can inform development of new diagnostic, personalized medicine, and
      forensic modalities. Prior research has demonstrated the feasibility of applying
      machine learning methods to perform body site and subject classification with
      microbiomic data. However, it is currently unknown which classifiers perform best
      among the many available alternatives for classification with microbiomic data.
      RESULTS: In this work, we performed a systematic comparison of 18 major
      classification methods, 5 feature selection methods, and 2 accuracy metrics using
      8 datasets spanning 1,802 human samples and various classification tasks: body
      site and subject classification and diagnosis. CONCLUSIONS: We found that random
      forests, support vector machines, kernel ridge regression, and Bayesian logistic
      regression with Laplace priors are the most effective machine learning techniques
      for performing accurate classification from these microbiomic data.

PMID- 24456582
TI  - Assessment of liver stiffness in patients with HCV and mixed cryoglobulinemia
      undergoing rituximab treatment.
AB  - INTRODUCTION: Mixed cryoglobulinemia (MC) is a HCV-related lymphoproliferative
      disorder generally associated with advanced liver disease. Liver stiffness has
      been significantly correlated with histopathological stage of fibrosis. Moreover,
      it was influenced by necroinflammatory activity. Rituximab (RTX) is a chimeric
      anti-CD20 monoclonal antibody inducing transient B lymphocytes depletion that was
      shown to be useful and safe in the majority of HCV MC patients, leading also to
      improvement of cirrhotic syndrome. Aim of this study was to evaluate the
      modifications of liver stiffness following RTX treatment in HCV-related MC
      patients. MATERIALS AND METHODS: Fourteen consecutive patients (10 F, 4 M; mean
      age 60.43 +/- 43) with HCV-related chronic hepatitis (n = 10) or cirrhosis (n =
      4) and MC, eligible for RTX treatment, were prospectively enrolled. Intravenous
      injection of 1 g of RTX was performed at day 0 and at day 15. Assessment of
      stiffness was carried out by Fibroscan (Echosens, Paris-France) at baseline, 15
      days after the first infusion, and at month 1, 3 and 6 after therapy. RESULTS: MC
      symptoms significantly improved during the study, especially during the first 3
      months. Liver stiffness observed 3 months after treatment was significantly
      reduced when compared with pre-treatment values (p = 0.01). This difference
      disappeared after 6 months of follow-up. Cytofluorimetric analysis showed a
      decrease of CD19+ peripheral blood cells, with the nadir at month 3 after therapy
      and B cell compartment reconstitution after 6 months. CONCLUSION: This study, for
      the first time showed that RTX-treatment in HCV-related MC induces a reduction of
      liver stiffness that is strictly associated with the B-cell depletion.

PMID- 24456584
TI  - Expression of glucosylceramide synthase in invasive ductal breast cancer may be
      correlated with high estrogen receptor status and low HER-2 status.
AB  - BACKGROUND AND OBJECTIVES: Breast cancer is one of the most common causes of
      cancer-related deaths in women worldwide. Studies on glucosylceramide synthase
      (GCS) activity suggest that this enzyme has a role in the development of
      multidrug resistance in many cancer cells. However, few studies have shown the
      expression of GCS in invasive ductal breast cancer and breast intraductal
      proliferative lesions. METHODS: In total, 196 samples from patients with invasive
      ductal breast cancer and 61 samples of breast intraductal proliferative lesions
      were collected. Immunohistochemical analyses were conducted to determine the
      expression of GCS and other related proteins. RESULTS: Expression of GCS was high
      in estrogen receptor (ER)-positive and HER-2 negative samples. In contrast, the
      expression of GCS in invasive ductal cancer was significantly lower than that in
      intraductal proliferative lesions. CONCLUSION: Our data demonstrates a
      correlation between the expression of the GCS protein and ER-positive/HER-2
      negative breast cancer. Furthermore, in contrast to previous reports, the
      expression of GCS protein was shown to be much higher in ductal carcinoma in-situ
      than that in invasive ductal cancer. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1559854430111589.

PMID- 24456585
TI  - Application of heart-rate variability in patients undergoing weaning from
      mechanical ventilation.
AB  - INTRODUCTION: The process of weaning may impose cardiopulmonary stress on
      ventilated patients. Heart-rate variability (HRV), a noninvasive tool to
      characterize autonomic function and cardiorespiratory interaction, may be a
      promising modality to assess patient capability during the weaning process. We
      aimed to evaluate the association between HRV change and weaning outcomes in
      critically ill patients. METHODS: This study included 101 consecutive patients
      recovering from acute respiratory failure. Frequency-domain analysis, including
      very low frequency, low frequency, high frequency, and total power of HRV was
      assessed during a 1-hour spontaneous breathing trial (SBT) through a T-piece and
      after extubation after successful SBT. RESULTS: Of 101 patients, 24 (24%) had SBT
      failure, and HRV analysis in these patients showed a significant decrease in
      total power (P = 0.003); 77 patients passed SBT and were extubated, but 13 (17%)
      of them required reintubation within 72 hours. In successfully extubated
      patients, very low frequency and total power from SBT to postextubation
      significantly increased (P = 0.003 and P = 0.004, respectively). Instead,
      patients with extubation failure were unable to increase HRV after extubation.
      CONCLUSIONS: HRV responses differ between patients with different weaning
      outcomes. Measuring HRV change during the weaning process may help clinicians to
      predict weaning results and, in the end, to improve patient care and outcome.

PMID- 24456586
TI  - Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma:
      pivotal study update demonstrates durable responses.
AB  - BACKGROUND: Romidepsin is a structurally unique, potent, bicyclic class 1
      selective histone deacetylase inhibitor approved by the US Food and Drug
      Administration for the treatment of patients with cutaneous T-cell lymphoma who
      have received >= 1 prior systemic therapy and patients with peripheral T-cell
      lymphoma (PTCL) who have received >= 1 prior therapy. Approval for PTCL was based
      on results (n = 130; median follow-up, 13.4 months) from the pivotal study of
      romidepsin for the treatment of relapsed/refractory PTCL. The objective is to
      present updated data (median follow-up, 22.3 months) and to characterize patients
      who achieved long-term responses (>= 12 months) to romidepsin. METHODS: Patients
      with PTCL who relapsed from or were refractory to >= 1 prior systemic therapy
      received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and
      15 every 28 days for up to 6 cycles; patients with response or stable disease
      could continue romidepsin beyond 6 cycles. The primary endpoint was rate of
      confirmed/unconfirmed complete response (CR/CRu) determined by an Independent
      Review Committee. Secondary endpoints included objective response rate (ORR) and
      duration of response (DOR). For patients who achieved CR/CRu, baseline
      characteristics by DOR (>= 12 vs < 12 months) were examined. RESULTS: The ORR to
      romidepsin was 25%, including 15% with CR/CRu. The median DOR for all responders
      was 28 months (range, < 1-48+) and was not reached for those who achieved CR/CRu.
      Patients with lack of response or transient response to prior therapy achieved
      durable responses with romidepsin. Of the 19 patients who achieved CR/CRu, 10 had
      long-term (>= 12 months) responses; none of the baseline characteristics examined
      including heavy pretreatment, response to prior therapy, or advanced disease
      precluded long-term responses to romidepsin. With a median progression-free
      survival of 29 months, patients who achieved CR/CRu for >= 12 months had
      significantly longer survival vs those with CR/CRu for < 12 months or < CR/CRu.
      Extended treatment and longer follow-up did not affect the reported safety
      profile of romidepsin. CONCLUSIONS: Treatment with romidepsin leads to highly
      durable responses in a subset of patients with relapsed/refractory PTCL, with
      responses ongoing as long as 48 months.

PMID- 24456588
TI  - Assessment of the oxidative stability of lubricant oil using fiber-coupled
      fluorescence excitation-emission matrix spectroscopy.
AB  - The fluorescence of antioxidant additives in lubricant oil was used as an
      indicator of oxidative stability of the oil. It was found that the decrease in
      fluorescence intensities of phenyl-alpha-napthylamine, its dimer, and another
      unidentified antioxidant coincide with the formation of decomposition products of
      the oil base stock. Simple kinetic models were developed that were capable of
      describing antioxidant reactions as a pseudo first-order processes. It is shown
      that fluorescence excitation emission matrix (EEM) spectroscopy coupled with an
      optical fiber probe can provide real-time assessment of the oxidative stability
      of the lubricant. Parallel factor (PARAFAC) analysis was used to correlate the
      component scores to the oil breakdown number. 

PMID- 24456587
TI  - Homocysteine metabolism in children with idiopathic nephrotic syndrome.
AB  - BACKGROUND: Homocysteine metabolism is altered in children with idiopathic
      nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early
      atherosclerosis and glomerulosclerosis and may occur at time of first occurrence
      of idiopathic nephrotic syndrome. METHODS: Thirty children with first episode of
      idiopathic nephrotic syndrome (FENS) aged 1-16 years along with 30 age- and sex
      matched healthy controls were enrolled in this study. Homocysteine and cysteine
      were measured with HPLC; vitamin B12 and folic acid were measured with electro
      chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine
      level in children with FENS and in controls. Secondary outcome measures were (1)
      plasma and urine homocysteine and cysteine levels in children with FENS at 12
      weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B12 and
      folic acid in children with FENS, at 12 weeks and 1 year (remission). RESULTS:
      Plasma homocysteine and cysteine levels were comparable to controls in children
      with FENS, at 12 weeks and 1-year remission. Plasma levels of vitamin B12 and
      folic acid were significantly decreased compared to controls in FENS due to
      increased urinary excretion, which normalize during remission at 12 weeks and 1
      year. Urinary homocysteine and cysteine levels were significantly raised in FENS
      compared to controls and continued to be raised even at 12-week and 1-year
      remission. CONCLUSION: Homocysteine metabolism is deranged in children with FENS.
      Renal effects of long-term raised urinary homocysteine levels need to be studied.

PMID- 24456589
TI  - The Successive Projections Algorithm for interval selection in trilinear partial
      least-squares with residual bilinearization.
AB  - In this work the Successive Projection Algorithm is presented for intervals
      selection in N-PLS for three-way data modeling. The proposed algorithm combines
      noise-reduction properties of PLS with the possibility of discarding
      uninformative variables in SPA. In addition, second-order advantage can be
      achieved by the residual bilinearization (RBL) procedure when an unexpected
      constituent is present in a test sample. For this purpose, SPA was modified in
      order to select intervals for use in trilinear PLS. The ability of the proposed
      algorithm, namely iSPA-N-PLS, was evaluated on one simulated and two experimental
      data sets, comparing the results to those obtained by N-PLS. In the simulated
      system, two analytes were quantitated in two test sets, with and without
      unexpected constituent. In the first experimental system, the determination of
      the four fluorophores (l-phenylalanine; l-3,4-dihydroxyphenylalanine; 1,4
      dihydroxybenzene and l-tryptophan) was conducted with excitation-emission data
      matrices. In the second experimental system, quantitation of ofloxacin was
      performed in water samples containing two other uncalibrated quinolones
      (ciprofloxacin and danofloxacin) by high performance liquid chromatography with
      UV-vis diode array detector. For comparison purpose, a GA algorithm coupled with
      N-PLS/RBL was also used in this work. In most of the studied cases iSPA-N-PLS
      proved to be a promising tool for selection of variables in second-order
      calibration, generating models with smaller RMSEP, when compared to both the
      global model using all of the sensors in two dimensions and GA-NPLS/RBL. 

PMID- 24456590
TI  - Sensitive pseudobienzyme electrocatalytic DNA biosensor for mercury(II) ion by
      using the autonomously assembled hemin/G-quadruplex DNAzyme nanowires for signal
      amplification.
AB  - Herein, a novel sensitive pseudobienzyme electrocatalytic DNA biosensor was
      proposed for mercury ion (Hg(2+)) detection by using autonomously assembled
      hemin/G-quadruplex DNAzyme nanowires for signal amplification. Thiol
      functionalized capture DNA was firstly immobilized on a nano-Au modified glass
      carbon electrode (GCE). In presence of Hg(2+), the specific coordination between
      Hg(2+) and T could result in the assembly of primer DNA on the electrode, which
      successfully triggered the HCR to form the hemin/G-quadruplex DNAzyme nanowires
      with substantial redox probe thionine (Thi). In the electrolyte of PBS containing
      NADH, the hemin/G-quadruplex nanowires firstly acted as an NADH oxidase to assist
      the concomitant formation of H2O2 in the presence of dissolved O2. Then, with the
      redox probe Thi as electron mediator, the hemin/G-quadruplex nanowires acted as
      an HRP-mimicking DNAzyme that quickly bioelectrocatalyzed the reduction of
      produced H2O2, which finally led to a dramatically amplified electrochemical
      signal. This method has demonstrated a high sensitivity of Hg(2+) detection with
      the dynamic concentration range spanning from 1.0 ng L(-1) to 10 mg L(-1) Hg(2+)
      and a detection limit of 0.5 ng L(-1) (2.5 pM) at the 3Sblank level, and it also
      demonstrated excellent selectivity against other interferential metal ions.

PMID- 24456591
TI  - Rapid and sensitive methodology for determination of ethyl carbamate in fortified
      wines using microextraction by packed sorbent and gas chromatography with mass
      spectrometric detection.
AB  - This work presents a new methodology to quantify ethyl carbamate (EC) in
      fortified wines. The presented approach combines the microextraction by packed
      sorbent (MEPS), using a hand-held automated analytical syringe, with one
      dimensional gas chromatography coupled with mass spectrometry detection (GC-MS).
      The performance of different MEPS sorbent materials was tested, namely SIL, C2,
      C8, C18, and M1. Also, several extraction solvents and the matrix effect were
      evaluated. Experimental data showed that C8 and dichloromethane were the best
      sorbent/solvent pair to extract EC. Concerning solvent and sample volumes
      optimization used in MEPS extraction an experimental design (DoE) was carried
      out. The best extraction yield was achieved passing 300 MUL of sample and 100 MUL
      of dichloromethane. The method validation was performed using a matrix-matched
      calibration using both sweet and dry fortified wines, to minimize the matrix
      effect. The proposed methodology presented good linearity (R(2)=0.9999) and high
      sensitivity, with quite low limits of detection (LOD) and quantification (LOQ),
      1.5 MUg L(-1) and 4.5 MUg L(-1), respectively. The recoveries varied between 97%
      and 106%, while the method precision (repeatability and reproducibility) was
      lower than 7%. The applicability of the methodology was confirmed through the
      analysis of 16 fortified wines, with values ranging between 7.3 and 206 MUg L(
      1). All chromatograms showed good peak resolution, confirming its selectivity.
      The developed MEPS/GC-MS methodology arises as an important tool to quantify EC
      in fortified wines, combining efficiency and effectiveness, with simpler, faster
      and affordable analytical procedures that provide great sensitivity without using
      sophisticated and expensive equipment.

PMID- 24456592
TI  - Facile preparation of surface-exchangeable core@shell iron oxide@gold
      nanoparticles for magnetic solid-phase extraction: use of gold shell as the
      intermediate platform for versatile adsorbents with varying self-assembled
      monolayers.
AB  - The core@shell Fe3O4@Au nanoparticles (NPs) functionalized with exchangeable self
      assembled monolayers have been developed for mode switching magnetic solid-phase
      extraction (MSPE) using high performance liquid chromatography with ultraviolet
      detection. The adsorbents were synthesized by chemical coprecipitation to prepare
      magnetic cores followed by sonolysis to produce gold shells. Functionalization of
      Fe3O4@Au NPs surface was realized through self-assembly of commercially available
      low molecular weight thiol-containing ligands using gold shells as intermediate
      platform and the dynamic nature of Au-S chemistry allowed substituent of one
      thiol-containing ligand with another simply by thiol exchange process. The
      resultant adsorbents were characterized by transmission electronic microscopy,
      Fourier transform infrared spectroscopy, elemental analysis, contact angle
      measurement, and vibrating sample magnetometry. To evaluate the versatile
      performance of the developed MSPE adsorbents, they were applied for normal-phase
      SPE followed by reversed-phase SPE. A few kinds of diphenols and polycyclic
      aromatic hydrocarbons (PAHs) were employed as model analytes, respectively. The
      predominant parameters affecting extraction efficiency were investigated and
      optimized. Under the optimum experimental conditions, wide dynamic linear range
      (6.25-1600 MUg L(-1) for diphenols and 1.56-100 MUg L(-1) for PAHs) with good
      linearity (r(2)>=0.989) and low detection limits (0.34-16.67 MUg L(-1) for
      diphenols and 0.26-0.52 MUg L(-1) for PAHs) were achieved. The advantage of the
      developed method is that the Fe3O4@Au NPs could be reutilized for
      preconcentrating diverse target analytes in different SPE modes sequentially
      simply through treatment with desired thiol-containing ligands.

PMID- 24456593
TI  - On-line coupling of macroporous resin column chromatography with direct analysis
      in real time mass spectrometry utilizing a surface flowing mode sample holder.
AB  - A surface flowing mode sample holder was designed as an alternative sampling
      strategy for direct analysis in real time mass spectrometry (DART-MS). With the
      sample holder, the on-line coupling of macroporous resin column chromatography
      with DART-MS was explored and the new system was employed to monitor the column
      chromatography elution process of Panax notoginseng. The effluent from
      macroporous resin column was first diluted and mixed with a derivatization
      reagent on-line, and the mixture was then directly transferred into the
      ionization region of DART-MS by the sample holder. Notoginsenosides were
      methylated and ionized in a metastable helium gas stream, and was introduced into
      MS for detection. The on-line system showed reasonable repeatability with a
      relative standard deviation of 12.3% for the peak area. Three notoginsenosides,
      i.e. notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1, were simultaneously
      determined during the eluting process. The alteration of the chemical composition
      in the effluent was accurately identified in 9 min, agreeing well with the off
      line analysis. The presented technique is more convenient compared to the
      traditional UPLC method. These results suggest that the surface flowing mode DART
      MS has a good potential for the on-line process monitoring in the pharmaceutical
      industry.

PMID- 24456594
TI  - Isotopic variants of light and heavy L-pyroglutamic acid succinimidyl esters as
      the derivatization reagents for DL-amino acid chiral metabolomics identification
      by liquid chromatography and electrospray ionization mass spectrometry.
AB  - L-Pyroglutamic acid succinimidyl ester (L-PGA-OSu) and its isotopic variant (L
      PGA[d5]-OSu) were newly synthesized and evaluated as the chiral labeling reagents
      for the enantioseparation of amino acids, in terms of separation efficiency by
      reversed-phase chromatography and detection sensitivity by ESI-MS/MS. The
      enantiomers of amino acids were easily labeled with the reagents at 60 degrees C
      within 10 min in an alkaline medium containing triethylamine. Although all the
      diastereomers derived from 18 proteolytic amino acids could not be satisfactorily
      separated, the pairs of 9 amino acids were completely separated by reversed-phase
      chromatography using the small particle (1.7 MUm) ODS column (Rs=1.95-8.05). The
      characteristic daughter ions, i.e., m/z 84.04 and m/z 89.04, were detected from
      all the derivatives by the collision induced dissociation of the protonated
      molecular ions. A highly sensitive detection at a low-fmol level (0.5-3.2 fmol)
      was also obtained from the selected reaction monitoring (SRM) chromatograms. An
      isotope labeling strategy using light and heavy L-PGA-OSu for the differential
      analysis of the DL-amino acids in different sample groups is also presented in
      this paper. The differential analysis of biological sample (i.e., human serum)
      and food product (i.e., yogurt) were tried to demonstrate the efficiency of the
      proposed method. The ratios of the DL-amino acids in human serum samples, spiked
      with the different concentrations of D-amino acids, were determined by the
      procedures using L-PGA-OSu and L-PGA[d5]-OSu. The D/L ratios in the two sample
      groups at different concentrations of amino acids were similar to the theoretical
      values. Furthermore, the ratios of D/L-alanine values in different yogurt
      products were comparable to the ratios obtained from the d/l values using only
      light reagent (i.e., L-PGA-OSu). Consequently, the proposed strategy is useful
      for the differential analysis not only in biological samples but also in food
      products.

PMID- 24456595
TI  - Achieving second order advantage with multi-way partial least squares and
      residual bi-linearization with total synchronous fluorescence data of monohydroxy
      polycyclic aromatic hydrocarbons in urine samples.
AB  - An attractive approach to handle matrix interference in samples of unknown
      composition is to generate second- or higher-order data formats and process them
      with appropriate chemometric algorithms. Several strategies exist to generate
      high-order data in fluorescence spectroscopy, including wavelength time matrices,
      excitation-emission matrices and time-resolved excitation-emission matrices. This
      article tackles a different aspect of generating high-order fluorescence data as
      it focuses on total synchronous fluorescence spectroscopy. This approach refers
      to recording synchronous fluorescence spectra at various wavelength offsets.
      Analogous to the concept of an excitation-emission data format, total synchronous
      data arrays fit into the category of second-order data. The main difference
      between them is the non-bilinear behavior of synchronous fluorescence data.
      Synchronous spectral profiles change with the wavelength offset used for sample
      excitation. The work presented here reports the first application of total
      synchronous fluorescence spectroscopy to the analysis of monohydroxy-polycyclic
      aromatic hydrocarbons in urine samples of unknown composition. Matrix
      interference is appropriately handled by processing the data either with unfolded
      partial least squares and multi-way partial least squares, both followed by
      residual bi-linearization. 

PMID- 24456596
TI  - Ultrasensitive electrochemiluminescent aptasensor for ochratoxin A detection with
      the loop-mediated isothermal amplification.
AB  - In this study, we for the first time presented an efficient, accurate, rapid,
      simple and ultrasensitive detection system for small molecule ochratoxin A (OTA)
      by using the integration of loop-mediated isothermal amplification (LAMP)
      technique and subsequently direct readout of LAMP amplicons with a signal-on
      electrochemiluminescent (ECL) system. Firstly, the dsDNA composed by OTA aptamer
      and its capture DNA were immobilized on the electrode. After the target
      recognition, the OTA aptamer bond with target OTA and subsequently left off the
      electrode, which effectively decreased the immobilization amount of OTA aptamer
      on electrode. Then, the remaining OTA aptamers on the electrode served as inner
      primer to initiate the LAMP reaction. Interestingly, the LAMP amplification was
      detected by monitoring the intercalation of DNA-binding Ru(phen)3(2+) ECL
      indictors into newly formed amplicons with a set of integrated electrodes. The
      ECL indictor Ru(phen)3(2+) binding to amplicons caused the reduction of the ECL
      intensity due to the slow diffusion of Ru(phen)3(2+)-amplicons complex to the
      electrode surface. Therefore, the presence of more OTA was expected to lead to
      the release of more OTA aptamer, which meant less OTA aptamer remained on
      electrode for producing LAMP amplicons, resulting in less Ru(phen)3(2+)
      interlaced into the formed amplicons within a fixed Ru(phen)3(2+) amount with an
      obviously increased ECL signal input. As a result, a detection limit as low as 10
      fM for OTA was achieved. The aptasensor also has good reproducibility and
      stability.

PMID- 24456597
TI  - A gold@silica core-shell nanoparticle-based surface-enhanced Raman scattering
      biosensor for label-free glucose detection.
AB  - The gold nanostar@silica core-shell nanoparticles conjugated with glucose oxidase
      (GOx) enzyme molecules have been developed as the surface-enhanced Raman
      scattering (SERS) biosensor for label-free detection of glucose. The surface
      immobilized GOx enzyme catalyzes the oxidation of glucose, producing hydrogen
      peroxide. Under laser excitation, the produced H2O2 molecules near the Au
      nanostar@silica nanoparticles generate a strong SERS signal, which is used to
      measure the glucose concentration. The SERS signal of nanostar@silica~GOx
      nanoparticle-based sensing assay shows the dynamic response to the glucose
      concentration range from 25 MUM to 25 mM in the aqueous solution with the limit
      of detection of 16 MUM. The sensing assay does not show any interference when
      glucose co-exists with both ascorbic acid and uric acid. The sensor can be
      applied to a saliva sample.

PMID- 24456598
TI  - Recombinase polymerase and enzyme-linked immunosorbent assay as a DNA
      amplification-detection strategy for food analysis.
AB  - Polymerase chain reaction in conjunction with enzyme-linked immunosorbent assay
      (PCR-ELISA) is a well-established technique that provides a suitable rapid,
      sensitive, and selective method for a broad range of applications. However, the
      need for precise rapid temperature cycling of PCR is an important drawback that
      can be overcome by employing isothermal amplification reactions such as
      recombinase polymerase amplification (RPA). The RPA-ELISA combination is proposed
      for amplification at a low, constant temperature (40 degrees C) in a short time
      (40 min), for the hybridisation of labelled products to specific 5'-biotinylated
      probes/streptavidin in coated microtiter plates at room temperature, and for
      detection by colorimetric immunoassay. RPA-ELISA was applied to screen common
      safety threats in foodstuffs, such as allergens (hazelnut, peanut, soybean,
      tomato, and maize), genetically modified organisms (P35S and TNOS), pathogenic
      bacteria (Salmonella sp. and Cronobacter sp.), and fungi (Fusarium sp.).
      Satisfactory sensitivity and reproducibility results were achieved for all the
      targets. The RPA-ELISA technique does away with thermocycling and provides a
      suitable sensitive, specific, and cost-effective method for routine applications,
      and proves particularly useful for resource-limited settings.

PMID- 24456599
TI  - Field-amplified sample injection coupled with pseudo-isotachophoresis technique
      for sensitive determination of selected psychiatric drugs in human urine samples
      after dispersive liquid-liquid microextraction.
AB  - A field-amplified sample injection (FASI) technique was elaborated for fast and
      sensitive determination of selected central nervous system drugs in human urine
      samples. Factors affecting the sensitivity enhancement, such as background
      electrolyte (BGE) and the analytical matrix composition were optimized and
      discussed. Pseudo-isotachophoresis (p-ITP) mechanism contribution in
      preconcentration mechanism was discussed. All separations were performed in
      uncoated fused silica capillaries 50 MUm * 57 cm at 22 kV. The optimized
      analytical matrix was composed of 0.25 mM HCOOH in 90% (v/v) methanol, while BGE
      contained 45 mM TRIS/HCl (pH 2.20). The head-column injection was performed in
      0.25 mM HCOOH water solution (3s, 3.45 kPa). Sample was introduced into the
      capillary by electrokinetic injection (70 s, 5 kV) followed by short BGE plug
      (3s, 3.45 kPa). Seven psychiatric drugs (olanzapine, prochlorperazine dimaleate,
      trifluoperazine dihydrochloride, perphenazine, promazine hydrochloride,
      clomipramine hydrochloride, and chlorprothixene hydrochloride) were separated in
      about 6 min. The elaborated method was additionally supported with dispersive
      liquid-liquid microextraction (DLLME) technique which in summary with FASI
      provided about 8000-13,000-fold sensitivity enhancement in comparison to the
      capillary zone electrophoresis (CZE) method with standard hydrodynamic injection
      (5s, 3.45 kPa).

PMID- 24456600
TI  - NDM-1-producing strains, family Enterobacteriaceae, in hospital, Beijing, China.

PMID- 24456601
TI  - Antimalarial prophylaxis--efficacy or effectiveness?

PMID- 24456602
TI  - Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and
      epithelial-mesenchymal transition in retinal pigment epithelium cells.
AB  - The proliferation and epithelial-mesenchymal transition (EMT) of retinal pigment
      epithelium (RPE) cells are the major pathological changes in development of
      proliferative vitreoretinopathy (PVR), which leads to severe visual impairment.
      Histone deacetylases (HDACs)-mediated epigenetic mechanisms play important roles
      in controlling various physiological and pathological events. However, whether
      HDACs are involved in the regulation of proliferation and EMT in PRE cells
      remains unidentified. In this study, we evaluated the expression profile of HDAC
      family (18 genes) and found that some of class I and class II HDACs were up
      regulated in transforming growth factor-beta2 (TGF-beta2)/TGF-beta1-stimulated
      RPE cells. Tricostatin A (TSA), a class I and II HDAC inhibitor, suppressed the
      proliferation of RPE cells by G1 phase cell cycle arrest through inhibition of
      cyclin/CDK/p-Rb and induction of p21 and p27. In the meantime, TSA strongly
      prevented TGF-beta2-induced morphological changes and the up-regulation of alpha
      SMA, collagen type I, collagen type IV, fibronectin, Snail and Slug. We also
      demonstrated that TSA affected not only the canonical Smad signalling pathway but
      also the non-canonical TGF-beta/Akt, MAPK and ERK1/2 pathways. Finally, we found
      that the underlying mechanism of TSA affects EMT in RPE cells also through down
      regulating the Jagged/Notch signalling pathway. Therefore, this study may provide
      a new insight into the pathogenesis of PVR, and suggests that epigenetic
      treatment with HDAC inhibitors may have therapeutic value in the prevention and
      treatment of PVR. 

PMID- 24456603
TI  - Impact of the neural cell adhesion molecule-derived peptide FGL on seizure
      progression and cellular alterations in the mouse kindling model.
AB  - The neural cell adhesion molecule peptide mimetic fibroblast growth loop (FGL)
      proved to exert neuroprotective, neurotrophic, and anti-inflammatory effects in
      different in vitro and in vivo experiments. Based on this beneficial efficacy
      profile, it is currently in clinical development for neurodegenerative diseases
      and brain insults. Here, we addressed the hypothesis that the peptide might
      affect development of seizures in a kindling paradigm, as well as associated
      behavioral and cellular alterations. Both doses tested, 2 and 10 mg/kg FGL,
      significantly reduced the number of stimulations necessary to induce a
      generalized seizure. FGL did not exert relevant effects on the behavioral
      patterns of kindled animals. As expected, kindling increased the hippocampal cell
      proliferation rate. Whereas the low dose of FGL did not affect this kindling
      associated alteration, 10 mg/kg FGL proved to attenuate the expansion of the
      doublecortin-positive cell population. These data suggest that FGL administration
      might have an impact on disease-associated alterations in the hippocampal
      neuronal progenitor cell population. In conclusion, the effects of the peptide
      mimetic FGL in the kindling model do not confirm a disease-modifying effect with
      a beneficial impact on the development or course of epilepsy. The results
      obtained with FGL rather raise some concern regarding a putative effect, which
      might promote the formation of a hyperexcitable network. Future studies are
      required to further assess the risks in models with development of spontaneous
      seizures. 

PMID- 24456604
TI  - Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide
      nanoparticles.
AB  - In this research we employed layered double hydroxide nanoparticles (LDHs) to
      simultaneously deliver an anticancer drug 5-fluorouracil (5-FU) and Allstars Cell
      Death siRNA (CD-siRNA) for effective cancer treatment. The strategy takes
      advantage of the LDH anion exchange capacity to intercalate 5-FU into its
      interlayer spacing and load siRNA on the surface of LDH nanoparticles. LDH
      nanoparticles have been previously demonstrated as an effective cellular delivery
      system for 5-FU and siRNA separately in various investigations. More excitedly,
      the combination of CD-siRNA and anticancer drug 5-FU with the same LDH particles
      significantly enhanced cytotoxicity to three cancer cell lines, e.g. MCF-7, U2OS
      and HCT-116, compared to the single treatment with either CD-siRNA or 5-FU. This
      enhancement is probably a result of coordinate mitochondrial damage process.
      Thus, the strategy to co-deliver siRNA and an anticancer drug by LDHs has great
      potential to overcome the drug resistance and enhance cancer treatment. 

PMID- 24456605
TI  - Dynamic disordering of liposomal cocktails and the spatio-temporal favorable
      release of cargoes to circumvent drug resistance.
AB  - Multidrug resistance (MDR) has been a major impediment to the success of cancer
      chemotherapy. Extensive efforts have been devoted to the development of drug
      delivery systems using nanotechnology to reverse MDR in cancer. However, the
      spontaneous release of drug payloads was always a slow process, which leads to
      the low intracellular drug concentration resulting in consequent drug
      insensitivity. To circumvent this limitation, we described a liposomal cocktail
      (LMDHV) constructed by a pH-responsive molecule (i.e., malachite green carbinol
      base (MG)) and liposome conjugated with Her-2 antibody for codelivery of
      doxorubicin (DOX) and verapamil (VER) to suppress drug resistance in Her-2
      positive breast cancer. MG inserted in the bilayer as pH responders greatly
      contributed to the destabilization of the vesicle membrane in low pH, followed by
      the rapid release of the payloads. LMDHV showed 6-fold reversal efficiency in DOX
      resistant breast cancer owing to the efficient tumor targeting delivery and rapid
      burst release of drug intracellularly. Compared to tumor inhibition ratio of
      treated groups by free DOX (32.4 +/- 7.4%), our designed kinetically favorable
      drug release system exhibited significantly (P < 0.01) enhanced tumor inhibition
      ratio up to 83.9 +/- 12.5%, which is attributed to the remarkably increased drug
      concentration in cells. The spatio-temporal favorable release of drugs resulted
      in synergistic inhibition of tumor growth in xenografts. We envision that this
      new type of liposomal cocktail might be potentially utilized to circumvent drug
      resistance in the future.

PMID- 24456606
TI  - Engineering hybrid polymer-protein super-aligned nanofibers via rotary jet
      spinning.
AB  - Cellular microenvironments are important in coaxing cells to behave collectively
      as functional, structured tissues. Important cues in this microenvironment are
      the chemical, mechanical and spatial arrangement of the supporting matrix in the
      extracellular space. In engineered tissues, synthetic scaffolding provides many
      of these microenvironmental cues. Key requirements are that synthetic scaffolds
      should recapitulate the native three-dimensional (3D) hierarchical fibrillar
      structure, possess biomimetic surface properties and demonstrate mechanical
      integrity, and in some tissues, anisotropy. Electrospinning is a popular
      technique used to fabricate anisotropic nanofiber scaffolds. However, it suffers
      from relatively low production rates and poor control of fiber alignment without
      substantial modifications to the fiber collector mechanism. Additionally, many
      biomaterials are not amenable for fabrication via high-voltage electrospinning
      methods. Hence, we reasoned that we could utilize rotary jet spinning (RJS) to
      fabricate highly aligned hybrid protein-polymer with tunable chemical and
      physical properties. In this study, we engineered highly aligned nanofiber
      constructs with robust fiber alignment from blends of the proteins collagen and
      gelatin, and the polymer poly-epsilon-caprolactone via RJS and electrospinning.
      RJS-spun fibers retain greater protein content on the surface and are also
      fabricated at a higher production rate compared to those fabricated via
      electrospinning. We measured increased fiber diameter and viscosity, and
      decreasing fiber alignment as protein content increased in RJS hybrid fibers. RJS
      nanofiber constructs also demonstrate highly anisotropic mechanical properties
      mimicking several biological tissue types. We demonstrate the bio-functionality
      of RJS scaffold fibers by testing their ability to support cell growth and
      maturation with a variety of cell types. Our highly anisotropic RJS fibers are
      therefore able to support cellular alignment, maturation and self-organization.
      The hybrid nanofiber constructs fabricated by RJS therefore have the potential to
      be used as scaffold material for a wide variety of biological tissues and organs,
      as an alternative to electrospinning. 

PMID- 24456607
TI  - Human endothelial cell-based assay for endotoxin as sensitive as the conventional
      Limulus Amebocyte Lysate assay.
AB  - Endotoxin, also known as lipopolysaccharide (LPS) produced by bacteria can be
      present in any liquid or on any biomaterial even if the material is sterile.
      Endotoxin in mammals can cause fever, inflammation, cell and tissue damage and
      irreversible septic shock and death. In the body, endothelial cells making up the
      blood vasculature and endothelial cells in vitro rapidly react to minute amounts
      of endotoxin resulting in a rapid induction of the cell adhesion molecule E
      selectin. In this study we have used immunofluorescent staining to evaluate the
      expression of E-selectin on human microvascular endothelial cells from the skin
      (HDMEC) and human umbilical vein endothelial cells (HUVEC) exposed to various
      concentrations of LPS. In addition, the sensitivity of detection was compared
      with the most widely used assay for the presence of endotoxin, the Limulus
      Amebocyte Lysate assay (LAL). The detection of E-selectin on endothelial cells in
      the presence of LPS for 4 h was found to be at least as sensitive in detecting
      the same concentration using the LAL assay. A cell adhesion molecule-enzyme
      immunosorbent assay was also developed and used to quantify LPS using the
      endothelial cell model. A comparison of LAL and the immunofluorescent staining
      method was carried out with solutions, nanoparticles, biomaterial extracts and
      endothelial cells grown directly on biomaterials. Under all conditions, the
      endothelial/E-selectin model system was positive for the test samples that were
      positive by LAL. Thus, we propose the use of this highly sensitive, rapid,
      reproducible assay for the routine testing of endotoxin in all steps in the
      manufacturing process of materials destined for use in humans. This can give a
      rapid feedback and localization of bacterial contamination sources with the LAL
      being reserved for the testing of the final product.

PMID- 24456608
TI  - Effect of renal angioembolization on post-traumatic acute kidney injury after
      high-grade renal trauma: a comparative study of 52 consecutive cases.
AB  - BACKGROUND: Acute kidney injury (AKI) is associated with unfavourable outcomes
      and higher mortality after trauma. Renal angioembolization (RAE) has proved
      efficiency in the management of high-grade renal trauma (HGRT), but inevitably
      expose to unavoidable ischaemic areas or contrast medium nephrotoxicity which may
      impair renal function in the following hours. The aim of this study was to assess
      the potential acute impact of RAE on renal function in a consecutive series of
      HGRTs treated nonoperatively. MATERIALS AND METHODS: Of 101 cases of renal trauma
      admitted to our Regional Trauma Center between January 2005 and January 2010, 52
      cases of HGRT were treated nonoperatively; they were retrospectively classified
      into 2 groups according to whether RAE was used. Incidence and progression of AKI
      (RIFLE classification), maximum increase in serum creatinine (SCr), level since
      admission and recovery of renal function at discharge were compared between the
      groups. Multivariable analysis was performed to determine the role of RAE as an
      independent risk factor of AKI. RESULTS: RAE was performed in 10 patients within
      the first 48h. The RAE and no RAE groups were comparable in terms of severity
      score, renal injury grade, and level of SCr on admission. AKI incidence (RIFLE
      score Risk or worse) after 48 and 96h was 33% and 10%, respectively and did not
      differ significantly between groups at 48h (p=1.00) or 96h (p=1.00). The median
      maximum increase in SCr was significantly higher in no RAE than RAE group (30.4%
      vs. 6.9%, p=0.04). RAE was not found to be a significant variable in a multiple
      linear regression analysis predicting maximum SCr rise (p=0.34). SCr at discharge
      was >120% of baseline in only 5 patients, with no difference according to RAE
      (p=0.24). CONCLUSION: In a population of nonoperatively treated HGRT, the
      incidence of AKI decreased from almost 30% to 10% at 48h and 96h. RAE proceeding
      did not seem to affect significantly the occurrence and course of AKI or renal
      recovery. The decision to use RAE should probably not be restricted by fear of
      worsening renal function.

PMID- 24456609
TI  - Accuracy and reliability of linear measurements using 3-dimensional computed
      tomographic imaging software for Le Fort I Osteotomy.
AB  - Our purpose was to compare the accuracy and reliability of linear measurements
      for Le Fort I osteotomy using volume rendering software. We studied 11 dried
      skulls and used cone-beam computed tomography (CT) to generate 3-dimensional
      images. Linear measurements were based on craniometric anatomical landmarks that
      were predefined as specifically used for Le Fort I osteotomy, and identified
      twice each by 2 radiologists, independently, using Dolphin imaging version
      11.5.04.35. A third examiner then made physical measurements using digital
      calipers. There was a significant difference between Dolphin imaging and the gold
      standard, particularly in the pterygoid process. The largest difference was
      1.85mm (LLpPtg L). The mean differences between the physical and the 3
      dimensional linear measurements ranged from -0.01 to 1.12mm for examiner 1, and 0
      to 1.85mm for examiner 2. Interexaminer analysis ranged from 0.51 to 0.93.
      Intraexaminer correlation coefficients ranged from 0.81 to 0.96 and 0.57 to 0.92,
      for examiners 1 and 2, respectively. We conclude that the Dolphin imaging should
      be used sparingly during Le Fort I osteotomy.

PMID- 24456610
TI  - Inhibition of human lung cancer cell proliferation and survival by wine.
AB  - BACKGROUND: Compounds of plant origin and food components have attracted
      scientific attention for use as agents for cancer prevention and treatment. Wine
      contains polyphenols that were shown to have anti-cancer and other health
      benefits. The survival pathways of Akt and extracellular signal-regulated kinase
      (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and
      survival. In this study, we examined the effects of wine on proliferation and
      survival of human Non-small cell lung cancer (NSCLC) cells and its effects on
      signaling events. METHODS: Human NSCLC adenocarcinoma A549 and H1299 cells were
      used. Cell proliferation was assessed by thymidine incorporation. Clonogenic
      assays were used to assess cell survival. Immunoblotting was used to examine
      total and phosphorylated levels of Akt, Erk and p53. RESULTS: In A549 cells red
      wine inhibited cell proliferation and reduced clonogenic survival at doses as low
      as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk
      phosphorylation while it increased the levels of total and phosphorylated p53
      (Ser15). Control experiments indicated that the anti-proliferative effects of
      wine were not mediated by the associated contents of ethanol or the polyphenol
      resveratrol and were independent of glucose transport into cancer cells. White
      wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and
      reduced Akt phosphorylation. The effects of both red and white wine on Akt
      phosphorylation were also verified in H1299 cells. CONCLUSIONS: Red wine inhibits
      proliferation of lung cancer cells and blocks clonogenic survival at low
      concentrations. This is associated with inhibition of basal and EGF-stimulated
      Akt and Erk signals and enhancement of total and phosphorylated levels of p53.
      White wine mediates similar effects albeit at higher concentrations. Our data
      suggest that wine may have considerable anti-tumour and chemoprevention
      properties in lung cancer and deserves further systematic investigation in animal
      models of lung cancer.

PMID- 24456612
TI  - Extraction bradycardia: a pilot case-crossover study.
AB  - PURPOSE: Significant vasovagal reaction is one of the untoward events in the
      course of simple extractions. The present study then aimed to record the
      patients' heart rate during the extraction procedure. MATERIALS AND METHODS:
      Informed consents were obtained in advance. Patients were placed in the dental
      chair and their heart rate was measured before /and prior to the anesthetic
      injection, during, and after dental extraction on a pulse oxymeter device. Data
      were analyzed using paired t-test. RESULTS: Sixty one patients were included. The
      mean heart rates of these patients prior, during, and after extraction were 88,
      86 and 81, respectively. Two by two comparisons showed a significant decrease in
      the mean heart rate during extraction compared to the baseline and also after
      extraction compared to both before and during extraction (p < 0.05 for all
      three). CONCLUSIONS: Despite the presence of sufficient local anesthesia and
      performing the extraction with the least trauma, a significant decrease in heart
      rate is evident.

PMID- 24456611
TI  - Epithelial-to-mesenchymal transition markers to predict response of Berberine in
      suppressing lung cancer invasion and metastasis.
AB  - BACKGROUND: The effects of berberine on the metastatic potential of lung cancer
      cells and its underlying mechanisms have not been fully elucidated. Since
      epithelial-to-mesenchymal transition is a cellular process associated with cancer
      invasion and metastasis, we attempted to investigate the potential use of
      berberine as an inhibitor of TGF-beta1-induced epithelial-to-mesenchymal in A549
      cells. METHODS: In this study, we investigated the anticancer activity of
      berberine against A549 cells in vitro and in vivo. BBR-induced apoptosis of the
      human lung cancer cells was determined by flow cytometry. The ability of BBR to
      inhibit TGF-beta-induced EMT was examined by QRT-PCR and Western blotting. The
      impact of BBR on A549 cell migration and invasion was evaluated by transwell
      assay. RESULTS: We demonstrated that TGF-beta1 induced epithelial-to-mesenchymal
      to promote lung cancer invasion and metastasis. Berberine inhibited invasion and
      migration of A549 cells, increased expression of the epithelial phenotype marker
      E-cadherin, repressed the expression of the mesenchymal phenotype marker
      Vimentin, as well as decreased the level of epithelial-to-mesenchymal -inducing
      transcription factors Snail1 and Slug during the initiation of TGF-beta1-induced
      epithelial-to-mesenchymal. Furthermore, berberine inhibited growth of lung cancer
      cells in vivo xenograft. CONCLUSIONS: Our findings provided new evidence that
      berberine is an effective inhibitor of the metastatic potential of A549 cells
      through suppression of TGF-beta1-induced epithelial-to-mesenchymal.

PMID- 24456613
TI  - Lung protection during non-invasive synchronized assist versus volume control in
      rabbits.
AB  - INTRODUCTION: Experimental work provides insight into potential lung protective
      strategies. The objective of this study was to evaluate markers of ventilator
      induced lung injury after two different ventilation approaches: (1) a
      "conventional" lung-protective strategy (volume control (VC) with low tidal
      volume, positive end-expiratory pressure (PEEP) and paralysis), (2) a
      physiological approach with spontaneous breathing, permitting synchrony,
      variability and a liberated airway. For this, we used non-invasive Neurally
      Adjusted Ventilatory Assist (NIV-NAVA), with the hypothesis that liberation of
      upper airways and the ventilator's integration with lung protective reflexes
      would be equally lung protective. METHODS: In this controlled and randomized in
      vivo laboratory study, 25 adult White New Zealand rabbits were studied, including
      five non-ventilated control animals. The twenty animals with aspiration-induced
      lung injury were randomized to ventilation with either VC (6 mL/kg, PEEP 5 cm
      H2O, and paralysis) or NIV-NAVA for six hours (PEEP = zero because of leaks).
      Markers of lung function, lung injury, vital signs and ventilator parameters were
      assessed. RESULTS: At the end of six hours of ventilation (n = 20), there were no
      significant differences between VC and NIV-NAVA for vital signs, PaO2/FiO2 ratio,
      lung wet-to-dry ratio and broncho-alveolar Interleukin 8 (Il-8). Plasma IL-8 was
      higher in VC (P <0.05). Lung injury score was lower for NIV-NAVA (P = 0.03).
      Dynamic lung compliance recovered after six hours in NIV-NAVA but not in VC (P
      <0.05). During VC, peak pressures increased from 9.2 +/- 2.4 cm H2O (hour 1) to
      12.3 +/- 12.3 cm H2O (hour 6) (P <0.05). During NIV-NAVA, the tracheal end
      expiratory pressure was similar to the end-expiratory pressure during VC. Two
      animals regurgitated during NIV-NAVA, without clinical consequences, and survived
      the protocol. CONCLUSIONS: In experimental acute lung injury, NIV-NAVA is as lung
      protective as VC 6 ml/kg with PEEP.

PMID- 24456614
TI  - Availability and practice of bedside ultrasonography in emergency rooms and
      prehospital setting: a French survey.
AB  - INTRODUCTION: The utility of bedside ultrasound (US) performed by emergency
      physicians has been proven for multiple purposes. There are no data about this
      technique in emergency departments (ED) in France. The primary objective is to
      determine the availability of ultrasound device (UD) in EDs and in prehospital
      settings in France. Minor objectives are to determine the number and type of UD,
      the most current applications of US and the factors correlated with availability
      of UDs in the setting of emergency medicine. METHODS: This is a cross-sectional,
      descriptive, multicenter survey from December 2010 to June 2011, including all
      EDs and prehospital units in France. A questionnaire was sent by e-mail. Non
      responders were contacted by telephone with one recall. RESULTS: The response
      rate was 74% (327/440) for EDs and 73% (278/379) for prehospital units. A UD is
      available in 52% (171/327) (CI 95% [46; 58]) of EDs and in 9% (25/278) (CI 95%
      [5; 13]) of prehospital units. Among departments having no access to UDs, 29% of
      EDs and 12% of prehospital units have plans to implement emergency physician
      performed US. The most common US applications are focused assessment with
      sonography for trauma and pleural exams. CONCLUSION: Availability of UDs in
      French public hospital EDs is 52% and 9% in prehospital units. Despite the
      progressive expansion of the technique over the last years, bedside
      ultrasonography is not yet completely integrated in the physical examination of
      the patient in an emergency situation in France. A reassessment will be required
      to confirm the current trend of expansion.

PMID- 24456615
TI  - [Penetrating neck injuries: importance of one systematic clinical examination
      associated with a MDCT angiography].

PMID- 24456616
TI  - [Nuclear magnetic resonance based metabolic phenotyping for patient evaluations
      in operating rooms and intensive care units].
AB  - Metabolic phenotyping consists in the identification of subtle and coordinated
      metabolic variations associated with various pathophysiological stimuli.
      Different analytical methods, such as nuclear magnetic resonance, allow the
      simultaneous quantification of a large number of metabolites. Statistical
      analyses of these spectra thus lead to the discrimination between samples and the
      identification of a metabolic phenotype corresponding to the effect under study.
      This approach allows the extraction of candidate biomarkers and the recovery of
      perturbed metabolic networks, driving to the generation of biochemical hypotheses
      (pathophysiological mechanisms, diagnostic tests, therapeutic targets...).
      Metabolic phenotyping could be useful in anaesthesiology and intensive care
      medicine for the evaluation, monitoring or diagnosis of life-threatening
      situations, to optimise patient managements. This review introduces the physical
      and statistical fundamentals of NMR-based metabolic phenotyping, describes the
      work already achieved by this approach in anaesthesiology and intensive care
      medicine. Finally, potential areas of interest are discussed for the
      perioperative and intensive management of patients, from newborns to adults. 

PMID- 24456617
TI  - Internet remote control of pump settings for postoperative continuous peripheral
      nerve blocks: a feasibility study in 59 patients.
AB  - INTRODUCTION: During continuous peripheral nerve blocks, infusion adjustments are
      essential for postoperative analgesia without side effects. Beside, physicians
      and nurse visits related to pump's settings and monitoring are time consuming and
      costly. We hypothesized that a remote control of pump's settings, by telemedicine
      transmission, adjusted to patients' feedbacks, is feasible and interesting in
      optimizing patient's postoperative pain management. METHODS: Fifty-nine ASA
      physical status I and II patients were included. Ropivacaine 0.2% was infused
      during 72 h in CPNB catheters. After returning to the surgical ward, the patient
      was allowed to answer a 10 indicators questionnaire 3 times a day (8.00 AM, 2.00
      PM, 8.00 PM), or unlimited on patient's demand. This information was transmitted
      from the pump to a server through the Internet. If one indicator was out of the
      predefined thresholds, the anesthesiologist in charge was immediately informed by
      texto on his cell phone. The anesthesiologist connected to the website, checked
      the data from the patient and modified the settings of the pump by remote control
      according to a written protocol. The changes need a secure access with a password
      and a confirmation. The number of settings changes, the time to realize the
      procedure and the adverse events related to the technique were noted. When the
      catheter was removed, the pump was unassigned to the patient and the data
      archived. RESULTS: Thirty sciatic, 24 femoral and 5 interscalene catheters were
      inserted in 59 patients. Five catheters were accidentally removed before the end
      of the 72-h period. The median VAS pain values at rest and during movement were
      respectively at 2 and 3. Sixteen patients complained about numbness promoting 2
      (0-3) changes in pump settings; 9 about motor blockade with 1 (0-2) change; 5
      about difficulties for physiotherapy with 1 (0-3) change. The mean time of pump
      settings modification after response to questionnaire or voluntarily patient's
      alert was 15 +/- 2.2 minutes. Early physiotherapy in the surgical ward was
      totally uneventful in 54 patients. The mean value of satisfaction scale of the
      patients was 8.4 +/- 1.6. No adverse event necessitated a postoperative analgesia
      technique change. CONCLUSION: Remote control pump's feedbacks and e-settings for
      postoperative analgesia using CPNB permitted a real adaptation to patients'
      needs, complaints and pain VAS values without nurse and physician physical
      intervention.

PMID- 24456618
TI  - Impact of a goal-directed therapy protocol on postoperative fluid balance in
      patients undergoing liver transplantation: a retrospective study.
AB  - OBJECTIVE: Liver transplantation carries major risks during the perioperative
      period. Few studies focused on the hemodynamics of patients undergoing liver
      transplantation. The present study was aimed to evaluate the impact of the
      implementation of a protocol including goal-directed therapy in patients
      undergoing liver transplantation. Our first goal was to determine its impact on
      the fluid balance. Secondarily, we evaluated possible improvements in the patient
      outcomes. STUDY DESIGN: A before and after study. PATIENTS AND METHODS: Fifty
      patients undergoing liver transplantation were included during two successive six
      month periods. During the first period, the management of the patients was left
      at the discretion of the senior physicians (control group, n=25). During the
      second period, the patients were treated according to a predetermined protocol
      including a specific hemodynamic monitoring (protocol group, n=25). RESULTS: The
      fluid balance was negative in the protocol group and positive in the control
      group at 24h (-606mL vs. +3445mL, P<0.01) and 48h (-2315mL vs. +1170mL, P<0.01)
      after liver transplantation. The volume of the crystalloid administration was
      lower in the protocol group than in the control group (5000mL vs. 8000mL, P<0.01,
      and 1500mL vs. 6000mL, P<0.01, during surgery and 48h after liver
      transplantation, respectively). The duration of mechanical ventilation and
      postoperative ileus were significantly reduced in the protocol group, as compared
      with the control group, 20h vs. 94h (P<0.01) and 4days vs. 6days (P<0.01),
      respectively. CONCLUSION: For patients undergoing liver transplantation, the
      implementation of a protocol aiming to optimize hemodynamics was associated with
      reduced fluid balance and decreased requirement for mechanical ventilation and
      postoperative ileus duration.

PMID- 24456620
TI  - Root resorption, treatment time and extraction rate during orthodontic treatment
      with self-ligating and conventional brackets.
AB  - INTRODUCTION: This study determined the amount and severity of EARR (external
      apical root resorption) after orthodontic treatment with self-ligating (SL) and
      conventional (Non-SL) brackets. Differences regarding rate of extraction cases,
      appointments and treatment time were evaluated. MATERIAL AND METHODS: 213
      patients with a mean age of 12.4 +/- 2.2 years were evaluated retrospectively.
      The treatments were performed with SL brackets (n = 139, Smartclip, 3 M Unitek,
      USA) or Non-SL brackets (n = 74, Victory Series, 3 M Unitek, USA). Measurements
      of the crown and root length of the incisors were taken using panoramic
      radiographs. Three-factor analysis of variance (ANOVA) was performed for an
      appliance effect. RESULTS: There was no difference between patients treated with
      Non-SL or SL brackets regarding the amount (in percentage) of EARR (Non-SL: 4.5
      +/- 6.6 vs. SL: 3.0 +/- 5.6). Occurrence of severe EARR (sEARR) did also not
      differ between the two groups (Non-SL 0.5 vs. SL: 0.3). The percentage of
      patients with need of tooth extraction for treatment (Non SL: 8.1 vs. SL: 6.9)
      and the number of appointments (Non-SL: 12.4 +/- 3.4 vs. SL: 13.9 +/- 3.3) did
      not show any differences. The treatment time was shorter with Non-SL brackets
      (Non-SL: 18.1 +/- 5.3 vs. SL: 20.7 +/- 4.9 months). CONCLUSIONS: This is the
      largest study showing that there is no difference in the amount of EARR, number
      of appointments and extraction rate between conventional and self-ligating
      brackets. For the first time we could demonstrate that occurrence of sEARR does
      not differ between the two types of brackets.

PMID- 24456621
TI  - Addicted to secrete - novel concepts and targets in cancer therapy.
AB  - The unfolded protein response (UPR) mediates the adaptation of the secretory
      pathway (SP) to fluctuations in cellular protein demand or to environmental
      variations. Recently, drug screenings have confirmed the therapeutic potential of
      targeting the UPR in cancer models. However, the UPR may not be the only
      druggable target of the SP. Moreover, recent studies have revealed other
      contributions of the SP to cancer development. This article does not intend to
      describe the well-established implication of UPR signaling pathways in cancer
      cell life and cell decision, but rather aims at defining the concept of 'tumor
      cell secretory addiction', from molecular, cellular, and therapeutic
      perspectives. Furthermore, the implication of UPR modulations in this context
      will be discussed. 

PMID- 24456622
TI  - Assessment of cerebral blood flow changes in nonconvulsive status epilepticus in
      comatose patients: a pathophysiological transcranial Doppler study.
AB  - PURPOSE: We assessed the accuracy of transcranial Doppler (TCD) in helping to
      diagnose nonconvulsive status epilepticus (NCSE) in comatose patients admitted to
      the intensive care unit (ICU) for acute neurological disorders at high risk for
      NCSE. METHODS: A 2-year prospective observational study in 38 consecutive
      patients requiring continuous electroencephalography (EEG) monitoring and
      intracranial pressure monitoring with TCD. RESULTS: Of the 38 patients, 10
      (26.3%) had NCSE by continuous EEG monitoring. Bilateral mean and maximal
      systolic and diastolic TCD velocities were significantly different between
      patients with and those without NCSE. Areas under the receiver-operating
      characteristic (ROC) curves of mean and maximal systolic velocities by TCD were
      0.82 (95% CI, 0.64-1.00) and 0.79 (95% CI, 0.62-0.95) with cutoffs of 95 cm/s and
      105 cm/s, respectively. Areas under the ROC curves of mean and maximal diastolic
      velocities were 0.76 (95% CI, 0.56-0.95) and 0.78 (95% CI, 0.60-0.96) with
      cutoffs of 31 cm/s and 40 cm/s, respectively. For none of the velocity parameters
      did the areas under the ROC curves differ significantly between the left and
      right sides. The best performance was obtained using mean systolic (SV) and a
      cutoff of 95 cm/s, which yielded a positive likelihood ratio of 3.8 and a
      negative likelihood ratio of 0.25. CONCLUSION: Our preliminary results showed a
      significant association between increased TCD velocities and NCSE in comatose
      patients. However, the likelihood ratios suggested a limited role for TCD in
      helping to diagnose seizure activity. Further studies with larger samples of NCSE
      patients are warranted to determine the exact contribution of TCD for NCSE
      detection in comatose ICU patients.

PMID- 24456623
TI  - The association between periodontal disease and seizure severity in refractory
      epilepsy patients.
AB  - PURPOSE: Periodontal diseases are common in most populations and affect people at
      all socioeconomic levels. Evidence suggests that patients with epilepsy actually
      have higher risks of dental disease and increased oral health needs, but the
      frequency and consequences of poor controlled seizures on dental and periodontal
      health have not been reported before. We aimed to assess the impact of seizure
      frequency on periodontal status and oral hygiene in a sample of epilepsy
      patients. METHODS: One hundred and nine consecutive patients treated for epilepsy
      at the outpatient clinic of our University Hospital were invited to take part in
      an oral examination to determine their periodontal disease status, together with
      a control group. In addition, seizure frequency and use of medication were
      documented. RESULTS: In logistic regression model, patients were significantly
      more susceptible to bad oral hygiene, gingivitis and periodontitis that controls
      (p<0.001); seizure frequency was significantly related to bad oral hygiene
      (p=0.010), gingivitis (p<0.001) and periodontitis (p<0.001). Tooth brushing
      habits and presence of caries were associated with oral health in patients group.
      CONCLUSION: Our study found a significant positive correlation between
      periodontal disease and seizure severity. Epilepsy patients need to focus more on
      their oral health and quality of oral hygiene.

PMID- 24456624
TI  - Synthetic HIV-1 matrix protein p17-based AT20-KLH therapeutic immunization in HIV
      1-infected patients receiving antiretroviral treatment: A phase I safety and
      immunogenicity study.
AB  - BACKGROUND: Therapeutic vaccination is a promising novel approach to treat HIV-1
      infected people by boosting or redirecting immune system to neutralize critical
      HIV-1 antigens whose biological effects are relevant in the context of viral
      pathogenesis. With the aim to induce neutralizing antibodies to the matrix
      protein p17 we have developed a peptide-based immunogen (AT20-KLH) and evaluated
      its safety and immunogenicity. METHODOLOGY: Twenty four asymptomatic HAART
      treated HIV-1+ patients were enrolled in a phase I clinical study and were
      randomized to three groups: 2 groups were treated with five IM injection (Arm A:
      25MUg/inoculation; Arm B: 100MUg/inoculation) at day (D) D0, D28, D56, D84 and
      D112; the control group (Arm C) were not injected. Safety was assessed by
      monitoring local and systemic adverse events (AEs), recorded till D168.
      Evaluation of immunogenicity was by titering antibodies at D0, D35, D56, D63,
      D84, D91, D112, D140 and D168 using ELISA. RESULTS: In all, 105 local and
      systemic AEs were reported across the three groups. Most were mild and resolved
      without sequelae. Also the few unsolicited events, deemed unrelated to the study
      vaccines, caused no problems. No significant changes in the routine laboratory
      parameters, CD4 T-cell count or HIV-1 viremia were found. At the time of
      enrollment 23 out of 24 patients had no anti-AT20 antibodies, whereas 11
      exhibited anti-p17 antibodies. Irrespective of the presence of preimmunization
      antibodies, all subjects developed high titers of anti-AT20 antibodies (GM 9775)
      in response to both AT20-KLH doses. These antibodies were also capable of
      recognizing AT20 within the p17 framework. CONCLUSIONS: The AT20 peptide-based
      approach has allowed to redirect HAART-treated patients' humoral responses toward
      a previously untargeted hotspot of functional activity. Overall, the tested AT20
      KLH doses were safe and well tolerated, supporting further exploration of AT20
      KLH as an HIV-1 therapeutic vaccine candidate.

PMID- 24456626
TI  - Statistical methods for the assessment of EQAPOL proficiency testing: ELISpot,
      Luminex, and Flow Cytometry.
AB  - In September 2011 Duke University was awarded a contract to develop the National
      Institutes of Health/National Institute of Allergy and Infectious Diseases
      (NIH/NIAID) External Quality Assurance Program Oversight Laboratory (EQAPOL).
      Through EQAPOL, proficiency testing programs are administered for Interferon
      gamma (IFN-gamma) Enzyme-linked immunosorbent spot (ELISpot), Intracellular
      Cytokine Staining Flow Cytometry (ICS) and Luminex-based cytokine assays. One of
      the charges of the EQAPOL program was to apply statistical methods to determine
      overall site performance. We utilized various statistical methods for each
      program to find the most appropriate for assessing laboratory performance using
      the consensus average as the target value. Accuracy ranges were calculated based
      on Wald-type confidence intervals, exact Poisson confidence intervals, or via
      simulations. Given the nature of proficiency testing data, which has repeated
      measures within donor/sample made across several laboratories; the use of mixed
      effects models with alpha adjustments for multiple comparisons was also explored.
      Mixed effects models were found to be the most useful method to assess laboratory
      performance with respect to accuracy to the consensus. Model based approaches to
      the proficiency testing data in EQAPOL will continue to be utilized. Mixed
      effects models also provided a means of performing more complex analyses that
      would address secondary research questions regarding within and between
      laboratory variability as well as longitudinal analyses. 

PMID- 24456625
TI  - Yellow fever vaccine-associated adverse events following extensive immunization
      in Argentina.
AB  - As a consequence of YF outbreaks that hit Brazil, Argentina, and Paraguay in 2008
      2009, a significant demand for YF vaccination was subsequently observed in
      Argentina, a country where the usual vaccine recommendations are restricted to
      provinces that border Brazil, Paraguay, and Bolivia. The goal of this paper is to
      describe the adverse events following immunization (AEFI) against YF in Argentina
      during the outbreak in the northeastern province of Misiones, which occurred from
      January 2008 to January 2009. During this time, a total of nine cases were
      reported, almost two million doses of vaccine were administered, and a total of
      165 AEFI were reported from different provinces. Case study analyses were
      performed using two AEFI classifications. Forty-nine events were classified as
      related to the YF vaccine (24 serious and 1 fatal case), and 12 events were
      classified as inconclusive. As the use of the YF 17D vaccine can be a challenge
      to health systems of countries with different endemicity patterns, a careful
      clinical and epidemiological evaluation should be performed before its
      prescription to minimize serious adverse events. 

PMID- 24456627
TI  - Cryopreservation of human monocytes for pharmacopeial monocyte activation test.
AB  - EU Directive 2010/63/EU regarding the protection of experimental animals came
      into force in November 2010 with an obligation for EU member states to
      incorporate its requirements into their respective national legislations by 1st
      of January 2013. The directive stipulates the application of in vitro methods to
      replace animal experiments whenever such an in vitro method exits and is
      recognized by EU legislation. The monocyte activation test (MAT) for the
      detection and quantification of pyrogenic contamination in medicines is
      recognized by the European Directorate for the Quality of Medicines & Health Care
      (EDQM) and was published in the European Pharmacopeia (Pharm. Eur.) in April
      2010. The methodology described here facilitates the use of the MAT by making
      monocytes available, in the form of cryopreserved human peripheral blood
      mononuclear cells (PBMCs). We have developed and qualified a procedure to prepare
      functional monocytes in the form of PBMCs from the leukocyte filters that are
      used for the separation of blood in blood donation centers. Once used, these
      filters are normally treated as biological waste. Here we describe the procedures
      that are critical for the successful cryopreservation of PBMCs, demonstrate
      protection of PBMC functionality using various ligands for the toll-like
      receptors (TLRs) that mediate pyrogenic responses, report validation of the
      methodology for linearity, precision and robustness and show examples of the
      practical application of cryopreserved in MATs with samples of drugs and
      vaccines. Another application of cryopreserved PBMCs, only mentioned here, is to
      serve as an alternative to freshly isolated PBMCs in tests for unwanted intrinsic
      pro-inflammatory activities of new biological therapeutics. Such tests use PBMCs
      or PBMCs over a layer of endothelial cells to detect (unwanted) cytokine release,
      PBMCs being more suited to this purpose than tests using whole blood. 

PMID- 24456628
TI  - An experimental framework for improved selection of binding proteins using SNAP
      display.
AB  - Display technologies (e.g. phage and ribosome display) are powerful tools for
      selecting and evolving protein binders against various target molecules. SNAP
      display is a DNA display technology that is conducted entirely in vitro: DNA
      encoding a library of variants is encapsulated in water-in-oil droplets wherein
      in vitro protein expression and covalent coupling to the encoding DNA occurs.
      Here, we explore critical factors for the successful performance of SNAP display
      based on a set of experiments designed to measure and quantify to what extent
      they affect selection efficiency. We find that, in SNAP display, the
      reconstituted cell free expression system PURExpress led to 1.5-fold more active
      protein and achieved 3.5-fold greater DNA recovery in model selections compared
      to the RTS 100 Escherichia coli lysate based expression system. We report on the
      influence parameters including droplet occupancy, valency and selection
      stringency have on recovery and enrichment. An improved procedure involving
      bivalent display and stringent selection against a model target, Her2, led to a
      10(7)-fold enrichment of a DARPin (H10-2-G3, known to bind Her2 with picomolar
      affinity) over a non-binding DARPin after three rounds of selection. Furthermore,
      when spiked into a mixture of DARPins with different affinities, DARPin H10-2-G3
      outcompeted all other variants demonstrating SNAP display's ability to
      efficiently resolve clones with affinities in the nano- to picomolar range. These
      data establish SNAP display as an in vitro protein engineering tool for isolating
      protein binders and provide a framework for troubleshooting affinity selections. 

PMID- 24456629
TI  - Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian
      patients.
AB  - BACKGROUND: Only a few Helicobacter pylori-infected individuals develop severe
      gastric diseases and virulence factors of H. pylori appear to be involved in such
      clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence
      factor of Helicobacter pylori that is associated with duodenal ulcer development
      and reduced risk for gastric carcinoma in some populations. The aims of the
      present study were to determine the presence of dupA gene and evaluate the
      association among dupA and other virulence factors including cagA and vacA in
      Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients
      (100 children and 105 adults). DNA was extracted and analyzed for the presence of
      H. pylori and its virulence factors using the polymerase chain reaction method.
      RESULTS: Patients with gastritis tested positive for H. pylori more frequently.
      The dupA gene was detected in 41.5% of them (85/205); cagA gene was found in 98
      isolates (47.8%) and vacA genotype s1/m1 in 50.2%, s1/m2 in 8.3%, s2/m2 in 36.6%,
      s2/m1 in 0.5% and s1/s2/m1/m2 in 4.4%. We also verified a significant association
      between cagA and dupA genes [p = 0.0003, relative risk (RR) 1.73 and confidence
      interval [CI] = 1.3-2.3]. The genotypes s1/m1 were also associated with dupA gene
      (p = 0.0001, RR: 1.72 and CI: 1.3-2.2). The same associations were found when
      analyzing pediatric and adult groups of patients individually. CONCLUSION: Ours
      results suggest that dupA is highly frequent in Brazilian patients and is
      associated with cagA gene and vacA s1/m1 genotype, and it may be considered an
      important virulence factor in the development of gastric diseases in adults or
      children.

PMID- 24456630
TI  - Finishing effectiveness of different archwires using SmartClipTM self-ligating
      brackets: a clinical study.
AB  - OBJECTIVES: The aim of this clinical prospective trial was to evaluate finishing
      effectiveness of stainless steel (SS) archwires versus titanium molybdenum alloy
      (TMA) archwires using SmartClipTM self-ligating brackets. SUBJECTS AND METHODS:
      Thirty-two patients were divided in two groups: a group of 21 (G1-SS) and a group
      of 12 (G2-TMA). The protocol consisted of two different finishing archwires
      coupled with self-ligating brackets: .019 * .025" SS archwires for G1-SS and .019
      * .025" TMA archwires for G2-TMA. Lateral cephalometric radiographs obtained at
      the beginning (T1) and end (T2) of treatment were used to assess the changes in
      incisor inclination, and measurements of irregularity index (LII), interdental
      widths, arch length (AL) and arch depth (AD) were made on dental casts to
      investigate changes associated with crowding correction. RESULTS: No significant
      differences from T1 to T2 were found for incisors proclination and AL changes.
      Statistically significant differences were found for LII (higher decrease in G1
      SS), maxillary AD (higher increase in G1-SS) and three interdental maxillary
      widths (higher in G1-SS). CONCLUSION: The statistically significant differences
      found were few and clinically negligible. Self-ligating brackets system coupled
      with .019 * .025" archwires showed good finishing effectiveness, but no
      clinically significant differences were found between SS and TMA.

PMID- 24456631
TI  - Evaluation of masseter muscle morphology in different types of malocclusions
      using cone beam computed tomography.
AB  - OBJECTIVES: To evaluate the length and orientation of masseter in different types
      of malocclusions using Cone Beam Computed Tomography (CBCT). METHODS: Samples of
      180 patients seeking orthodontic treatment at the University of Nevada, Las Vegas
      School of Dentistry, were included in the study. Pre-treatment multi-slice CBCT
      scans of these patients were divided into three anteroposterior groups: Class I
      subjects with ANB angle 0 degrees  to 5 degrees ; Class II subjects with ANB
      angle >5 degrees ; and Class III subjects with ANB angle <0 degrees . CBCT scans
      were also divided into three vertical groups: normodivergent subjects with
      mandibular plane angle 22 degrees  to 30 degrees ; hyperdivergent subjects with
      mandibular plane angle >30 degrees , hypodivergent subjects with mandibular plane
      angle <22 degrees . The masseter was identified and landmarks were placed on the
      anterior border, at the origin and insertion of the muscle in 3-D mode of the
      Dolphin Imaging 10.5 Premium software. The Frankfort Horizontal Plane was used as
      a reference plane and an angular measurement was obtained by intersection of a
      line produced by the masseter landmarks to calculate the orientation of the
      muscles. The length of the masseter was measured and data were analyzed using
      ANOVA and matched pairs test. RESULTS: ANOVA found significant differences in
      muscle length among the three vertical groups for both the left and right
      muscles. Paired t test showed significantly shorter muscle length for the
      hypodivergent group (43.3 +/- 4.0 mm) compared to the normodivergent group (45.6
      +/- 4.5 mm, P < 0.05) and shorter muscle length for the hyperdivergent group
      (42.3 +/- 4.7 mm) compared to the hypodivergent group, P < 0.05. No significant
      differences were found in muscle length among the three anteroposterior groups.
      However, significant differences in muscle orientation angle were found among the
      three anteroposterior groups (P < 0.05). Class II subjects were found to have the
      most acute orientation angle (67.2 +/- 6.6 degrees ) and Class III had the most
      obtuse orientation angle (81.6 +/- 6.8 degrees ). CONCLUSIONS: These results
      suggest that certain types of malocclusion may have different masseter lengths
      and orientations and these differences may have implications for the mechanical
      advantage in bite force. For example, Class III individuals may have greater bite
      force than Class II individuals because the muscle fibers are oriented more along
      the arch of closure.

PMID- 24456635
TI  - European college of orthodontics: Commission of Affiliation and Titularisation.

PMID- 24456636
TI  - Polymorphism of the merozoite surface protein-1 block 2 region in Plasmodium
      falciparum isolates from Mauritania.
AB  - BACKGROUND: The genetic diversity of Plasmodium falciparum has been extensively
      studied in various parts of the world. However, limited data are available from
      Mauritania. The present study examined and compared the genetic diversity of P.
      falciparum isolates in Mauritania. METHODS: Plasmodium falciparum isolates blood
      samples were collected from 113 patients attending health facilities in
      Nouakchott and Hodh El Gharbi regions. K1, Mad20 and RO33 allelic family of msp-1
      gene were determined by nested PCR amplification. RESULTS: K1 family was the
      predominant allelic type carried alone or in association with Ro33 and Mad20
      types (90%; 102/113). Out of the 113 P. falciparum samples, 93(82.3%) harboured
      more than one parasite genotype. The overall multiplicity of infection was 3.2
      genotypes per infection. There was no significant correlation between
      multiplicity of infection and age of patients. A significant increase of
      multiplicity of infection was correlated with parasite densities. CONCLUSIONS:
      The polymorphism of P. falciparum populations from Mauritania was high. Infection
      with multiple P. falciparum clones was observed, as well as a high multiplicity
      of infection reflecting both the high endemicity level and malaria transmission
      in Mauritania.

PMID- 24456637
TI  - Gamma-hydroxybutyrate, acting through an anti-apoptotic mechanism, protects
      native and amyloid-precursor-protein-transfected neuroblastoma cells against
      oxidative stress-induced death.
AB  - Clinical observations suggested that gamma-hydroxybutyrate (GHB) protects nerve
      cells against death but the direct proofs are missing. Here, we combined several
      approaches to investigate GHB capacity to protect human neuroblastoma SH-SY5Y
      cells against hydrogen peroxide (H2O2)-induced death. To increase the patho
      physiological relevancy of our study, we used native SH-SY5Y cells and SH-SY5Y
      cells stably transfected with the wild-type amyloid-precursor-protein (APPwt) or
      control-vector-pCEP4. Trypan Blue exclusion and MTT (3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyl-tetrazolium-bromide) assays combined with pharmacological analyses
      showed that H2O2 reduced native and genetically modified cell viability and APPwt
      transfected cells were the most vulnerable. Terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) and activated caspase-3 staining assessed
      by flow cytometry revealed a basally elevated apoptotic signal in APPwt
      transfected cells. Reverse-transcription, real-time quantitative polymerase chain
      reaction (qPCR) and Western blotting showed that mRNA and protein basal ratios of
      apoptotic modulators Bax/Bcl-2 were also high in APPwt-transfected cells. GHB
      efficiently and dose-dependently rescued native and genetically modified cells
      from H2O2-induced death. Interestingly, GHB, which strongly decreased elevated
      basal levels of TUNEL-staining, activated caspase 3-labeling and Bax/Bcl-2 in
      APPwt-transfected cells, also counteracted H2O2-evoked increased apoptotic
      markers in native and genetically modified SH-SY5Y cells. Since GHB did not
      promote cell proliferation, anti-apoptotic action through the down-regulation of
      Bax/Bcl-2 ratios and/or caspase 3 activity appears as a critical mechanism
      involved in GHB-induced protection of SH-SY5Y cells against APPwt-overexpression-
      or H2O2-evoked death. Altogether, these results, providing multi-parametric
      evidence for the existence of neuroprotective action of GHB, also open
      interesting perspectives for the development of GHB analog-based strategies
      against neurodegeneration or nerve cell death. 

PMID- 24456638
TI  - Body weight has no impact on self-esteem of minority children living in inner
      city, low-income neighborhoods: a cross-sectional study.
AB  - BACKGROUND: The relationship between body weight and self-esteem among
      underserved minority children is not well documented. METHODS: We measured the
      self-esteem profile using the Self-Perception Profile for Children among 910
      minority children at 17 Houston community centers. RESULTS: Weight status had no
      effect on any of the self-esteem scores among the minority children (P >= 0.21).
      Black children had higher scholastic competence than Hispanic children (P =
      0.05). Social acceptance was not affected by age, gender, and race/ethnicity (P
      >= 0.13). Significant age x gender (P = 0.006) and race x gender (P = 0.005)
      interactions were detected on athletic competence. The younger boys had higher
      athletic competence than the younger and older girls (P <= 0.01). The older boys
      had higher athletic competence than the older girls (P = 0.008) but their scores
      were not different from those of the younger girls (P = 0.07). Within each
      race/ethnicity group, boys had higher athletic competence than girls (P <= 0.03).
      Black boys had higher athletic competence than Hispanic girls (P = 0.007) but
      their scores were not different from those of the Hispanic boys (P = 0.08). Age
      and gender had no effect on physical appearance but black children had higher
      scores than Hispanic children (P = 0.05). Behavioral conduct was not affected by
      age, gender, or race/ethnicity (P >= 0.11). There was an age x gender interaction
      on global self-worth (P = 0.02) with boys having similar scores regardless of
      ages (P = 0.40) or ethnicity (P = 0.98). However, boys from both age groups had
      higher global self-worth than the older girls (P <= 0.04) but their scores were
      not different from those of the younger girls (P >= 0.07). CONCLUSIONS: For the
      first time, we documented that being normal weight did not necessarily guarantee
      positive self-esteem among minority children. Their self-esteem scores were
      similar to those found among children who were diagnosed with obesity and obesity
      related co-morbidities and lower than those reported among normal-weight white
      children. Therefore, activities to promote self-esteem are important when working
      with underserved minority children in order to promote a healthy lifestyle.

PMID- 24456639
TI  - Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent
      post-operative low cardiac output syndrome in children.
AB  - INTRODUCTION: The response to exogenous epinephrine (Ep) is difficult to predict
      given the multitude of factors involved such as broad pharmacokinetic and
      pharmacodynamic between-subject variabilities, which may be more pronounced in
      children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co
      administered with milrinone, in children who underwent open heart surgical repair
      for congenital defects following cardiopulmonary bypass, including associated
      variability factors. METHODS: Thirty-nine children with a high risk of low
      cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics,
      hemodynamic and metabolic effects were analyzed using the non-linear mixed
      effects modeling software MONOLIX. According to the final model, an Ep dosing
      simulation was suggested. RESULTS: Ep dosing infusions ranged from 0.01 to 0.23
      MUg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one
      compartment open model with linear elimination adequately described the Ep
      concentration-time courses. Bodyweight (BW) was the main covariate influencing
      clearance (CL) and endogenous Ep production rate (q0) via an allometric
      relationship: CL(BWi) = thetaCL x (BWi)3/4 and q0(BWi) = thetaq0 x (BWi )3/4. The
      increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep
      concentration were well described using an Emax model. The effect of age was
      significant on HR and MAP basal level parameters. Assuming that Ep stimulated the
      production rate of plasma glucose, the increases in plasma glucose and lactate
      levels were well described by turnover models without any significant effect of
      age, BW or exogenous glucose supply. CONCLUSIONS: According to this population
      analysis, the developmental effects of BW and age explained a part of the
      pharmacokinetic and pharmacodynamics between-subject variabilities of Ep
      administration in critically ill children. This approach ultimately leads to a
      valuable Ep dosing simulation which should help clinicians to determine an
      appropriate a priori dosing regimen.

PMID- 24456640
TI  - A rapid, inexpensive, and semi-quantitative method for determining pollen tube
      extension using fluorescence.
AB  - BACKGROUND: Pollen tubes extend rapidly when pollen grains are incubated in
      defined media. Tube extension requires many critical functions of plant cells
      including molecular signaling, cytoskeleton remodeling, secretion, and cell wall
      synthesis. Consequently, pollen tube growth has been established as a way to
      conduct primary screens of chemical libraries to identify compounds that perturb
      key cellular processes in plants. RESULTS: Here we report a simple, inexpensive,
      rapid and semi-quantitative method for measurement of pollen tube growth in
      microtiter plates. The method relies on Congo Red binding to pollen tubes and
      correlates dye fluorescence to tube length. CONCLUSIONS: This method can be used
      in any laboratory without specialized equipment, and has the potential to enable
      larger screens as chemical libraries grow and to make chemical screening
      accessible to researchers building specialized libraries designed to probe
      pathways in plant biology.

PMID- 24456641
TI  - Doxofylline, a novofylline inhibits lung inflammation induced by
      lipopolysacharide in the mouse.
AB  - RATIONAL: Doxofylline is a xanthine drug that has been used as a treatment for
      respiratory diseases for more than 30 years. In addition to doxofylline being a
      bronchodilator, some studies have indicated that doxofylline also has anti
      inflammatory properties, although little is known about the effect of this drug
      on lung inflammation. OBJECTIVES: We have investigated the actions of doxofylline
      against the effects of Escherichia coli LPS in the lungs of BALB/c mice. METHODS:
      Animals have been treated with doxofylline (0.1, 0.3 and 1 mg/kg i.p.) 24, -and 1
      h before, and 6 h after intra-nasal instillation of LPS (10 MUg/mouse). Readouts
      were performed 24 h later. RESULTS: Doxofylline at 1 and 0.3, but not at 0.1
      mg/kg, significantly inhibit neutrophil recruitment to the lung induced by LPS
      (LPS: 208.4 +/- 14.5 versus doxofylline: 1 mg/kg: 106.2 +/- 4.8; 0.3 mg/kg: 105.3
      +/- 10.7 * 10(4) cells/ml). Doxofylline significantly inhibited IL-6 and TNF
      alpha release into BAL fluid in comparison to LPS-treated animals (LPS: 1255.6 +/
      143.9 versus doxofylline 1 mg/kg: 527.7 +/- 182.9; 0.3 mg/kg: 823.2 +/- 102.3
      pg/ml). Intra-vital microscopy of the tracheal tissue demonstrated that
      doxofylline significantly reduced LPS-mediated leukocyte adhesion to the vessel
      wall (LPS: 5.9 +/- 2.4 versus doxofylline 0.3 mg/kg: 1.78 +/- 0.87 cells/100
      MUm/15 s). Similarly, intra-vital microscopy of cremaster muscle demonstrated
      that doxofylline significantly reduced LPS-mediated leukocyte transmigration
      across the blood vessel wall (LPS: 9.3 +/- 3.5 versus doxofylline0.3 mg/kg: 3.1
      +/- 1.87 cells/100 MUm(2)). Doxofylline (0.1-10 MUM) also reduced fMLP-induced
      leukocyte migration in vitro, achieving a maximum effect at 10 MUM (fMLP: 37.8 +/
      0.5 versus doxofylline 10 MUM: 15.1 +/- 1.2 cells * 10(4)/ml). CONCLUSION:
      Doxofylline inhibits LPS-induced inflammation in the lungs of mice.

PMID- 24456644
TI  - Using the Program Sustainability Assessment Tool to assess and plan for
      sustainability.
AB  - Implementing and growing a public health program that benefits society takes
      considerable time and effort. To ensure that positive outcomes are maintained
      over time, program managers and stakeholders should plan and implement activities
      to build sustainability capacity within their programs. We describe a 3-part
      sustainability planning process that programs can follow to build their
      sustainability capacity. First, program staff and stakeholders take the Program
      Sustainability Assessment Tool to measure their program's sustainability across 8
      domains. Next, managers and stakeholders use results from the assessment to
      inform and prioritize sustainability action planning. Lastly, staff members
      implement the plan and keep track of progress toward their sustainability goals.
      Through this process, staff can more holistically address the internal and
      external challenges and pressures associated with sustaining a program. We
      include a case example of a chronic disease program that completed the Program
      Sustainability Assessment Tool and engaged in program sustainability planning. 

PMID- 24456642
TI  - Loss of the neuroprotective factor Sphingosine 1-phosphate early in Alzheimer's
      disease pathogenesis.
AB  - BACKGROUND: The greatest genetic risk factor for late-onset Alzheimer's disease
      (AD) is the epsilon4 allele of Apolipoprotein E (ApoE). ApoE regulates secretion
      of the potent neuroprotective signaling lipid Sphingosine 1-phosphate (S1P). S1P
      is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1
      and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and
      synaptic strength in hippocampal neurons. S1P and its receptor family have been
      subject to intense pharmacological interest in recent years, following approval
      of the immunomodulatory drug Fingolimod, an S1P mimetic, for relapsing multiple
      sclerosis. RESULTS: We quantified S1P levels in six brain regions that are
      differentially affected by AD pathology, in a cohort of 34 post-mortem brains,
      divided into four groups based on Braak neurofibrillary tangle staging. S1P
      declined with increasing Braak stage, and this was most pronounced in brain
      regions most heavily affected by AD pathology. The S1P/sphingosine ratio was 66%
      and 64% lower in Braak stage III/IV hippocampus (p = 0.010) and inferior temporal
      cortex (p = 0.014), respectively, compared to controls. In accordance with this
      change, both SphK1 and SphK2 activity declined with increasing Braak pathology in
      the hippocampus (p = 0.032 and 0.047, respectively). S1P/sphingosine ratio was
      2.5-fold higher in hippocampus of ApoE2 carriers compared to ApoE4 carriers, and
      multivariate regression showed a significant association between APOE genotype
      and hippocampal S1P/sphingosine (p = 0.0495), suggesting a new link between APOE
      genotype and pre-disposition to AD. CONCLUSIONS: This study demonstrates loss of
      S1P and sphingosine kinase activity early in AD pathogenesis, and prior to AD
      diagnosis. Our findings establish a rationale for further exploring S1P receptor
      pharmacology in the context of AD therapy.

PMID- 24456645
TI  - The Program Sustainability Assessment Tool: a new instrument for public health
      programs.
AB  - INTRODUCTION: Public health programs can deliver benefits only if they are able
      to sustain programs, policies, and activities over time. Although numerous
      sustainability frameworks and models have been developed, there are almost no
      assessment tools that have demonstrated reliability or validity or have been
      widely disseminated. We present the Program Sustainability Assessment Tool
      (PSAT), a new and reliable instrument for assessing the capacity for program
      sustainability of various public health and other programs. METHODS: A
      measurement development study was conducted to assess the reliability of the
      PSAT. Program managers and staff (n = 592) representing 252 public health
      programs used the PSAT to rate the sustainability of their program. State and
      community-level programs participated, representing 4 types of chronic disease
      programs: tobacco control, diabetes, obesity prevention, and oral health.
      RESULTS: The final version of the PSAT contains 40 items, spread across 8
      sustainability domains, with 5 items per domain. Confirmatory factor analysis
      shows good fit of the data with the 8 sustainability domains. The subscales have
      excellent internal consistency; the average Cronbach's alpha is 0.88, ranging
      from 0.79 to 0.92. Preliminary validation analyses suggest that PSAT scores are
      related to important program and organizational characteristics. CONCLUSION: The
      PSAT is a new and reliable assessment instrument that can be used to measure a
      public health program's capacity for sustainability. The tool is designed to be
      used by researchers, evaluators, program managers, and staff for large and small
      public health programs.

PMID- 24456646
TI  - From menu to mouth: opportunities for sodium reduction in restaurants.
AB  - Restaurant foods can be a substantial source of sodium in the American diet.
      According to the Institute of Medicine, the significant contribution made by
      restaurants and food service menu items to Americans' sodium intake warrants
      targeted attention. Public health practitioners are uniquely poised to support
      sodium-reduction efforts in restaurants and help drive demand for lower-sodium
      products through communication and collaboration with restaurant and food service
      professionals and through incentives for restaurants. This article discusses the
      role of the public health practitioner in restaurant sodium reduction and
      highlights select strategies that have been taken by state and local
      jurisdictions to support this effort. 

PMID- 24456647
TI  - Color edges extraction using statistical features and automatic threshold
      technique: application to the breast cancer cells.
AB  - BACKGROUND: Color image segmentation has been so far applied in many areas;
      hence, recently many different techniques have been developed and proposed. In
      the medical imaging area, the image segmentation may be helpful to provide
      assistance to doctor in order to follow-up the disease of a certain patient from
      the breast cancer processed images. The main objective of this work is to rebuild
      and also to enhance each cell from the three component images provided by an
      input image. Indeed, from an initial segmentation obtained using the statistical
      features and histogram threshold techniques, the resulting segmentation may
      represent accurately the non complete and pasted cells and enhance them. This
      allows real help to doctors, and consequently, these cells become clear and easy
      to be counted. METHODS: A novel method for color edges extraction based on
      statistical features and automatic threshold is presented. The traditional edge
      detector, based on the first and the second order neighborhood, describing the
      relationship between the current pixel and its neighbors, is extended to the
      statistical domain. Hence, color edges in an image are obtained by combining the
      statistical features and the automatic threshold techniques. Finally, on the
      obtained color edges with specific primitive color, a combination rule is used to
      integrate the edge results over the three color components. RESULTS: Breast
      cancer cell images were used to evaluate the performance of the proposed method
      both quantitatively and qualitatively. Hence, a visual and a numerical assessment
      based on the probability of correct classification (PC), the false classification
      (Pf), and the classification accuracy (Sens(%)) are presented and compared with
      existing techniques. The proposed method shows its superiority in the detection
      of points which really belong to the cells, and also the facility of counting the
      number of the processed cells. CONCLUSIONS: Computer simulations highlight that
      the proposed method substantially enhances the segmented image with smaller error
      rates better than other existing algorithms under the same settings (patterns and
      parameters). Moreover, it provides high classification accuracy, reaching the
      rate of 97.94%. Additionally, the segmentation method may be extended to other
      medical imaging types having similar properties.

PMID- 24456648
TI  - Exon identity crisis: disease-causing mutations that disrupt the splicing code.
AB  - Cis-acting RNA elements control the accurate expression of human multi-exon
      protein coding genes. Single nucleotide variants altering the fidelity of this
      regulatory code and, consequently, pre-mRNA splicing are expected to contribute
      to the etiology of numerous human diseases. 

PMID- 24456650
TI  - Rapid and reliable detection of alpha-globin copy number variations by
      quantitative real-time PCR.
AB  - BACKGROUND: Alpha-thalassemia is the most common human genetic disease worldwide.
      Copy number variations in the form of deletions of alpha-globin genes lead to
      alpha-thalassemia while duplications of alpha-globin genes can cause a severe
      phenotype in beta-thalassemia carriers due to accentuation of globin chain
      imbalance. It is important to have simple and reliable methods to identify
      unknown or rare deletions and duplications in cases in which thalassemia is
      suspected but cannot be confirmed by multiplex gap-PCR. Here we describe a copy
      number variation assay to detect deletions and duplications in the alpha-globin
      gene cluster (HBA-CNV). RESULTS: Quantitative real-time PCR was performed using
      four TaqMan(r) assays which specifically amplify target sequences representing
      both the alpha-globin genes, the -alpha3.7 deletion and the HS-40 region. The
      copy number for each target was determined by the 2-DeltaDeltaCq method. To
      validate our method, we compared the HBA-CNV method with traditional gap-PCR in
      108 samples from patients referred to our laboratory for hemoglobinopathy
      evaluation. To determine the robustness of the four assays, we analyzed samples
      with and without deletions diluted to obtain different DNA concentrations. The
      HBA-CNV method identified the correct copy numbers in all 108 samples. All four
      assays showed the correct copy number within a wide range of DNA concentrations
      (3.2-100 ng/MUL), showing that it is a robust and reliable method. By using the
      method in routine diagnostics of hemoglobinopathies we have also identified
      several deletions and duplications that are not detected with conventional gap
      PCR. CONCLUSIONS: HBA-CNV is able to detect all known large deletions and
      duplications affecting the alpha-globin genes, providing a flexible and simple
      workflow with rapid and reliable results.

PMID- 24456649
TI  - Perceptions of veterinarians and producers concerning Johne's disease prevalence
      and control in US beef cow-calf operations.
AB  - BACKGROUND: Efforts to educate producers and veterinarians in the United States
      regarding the management, prevention and control of Mycobacterium avium
      subspecies paratuberculosis (MAP) infection have increased over recent years.
      While nationwide awareness about MAP infection is improving, current level of
      awareness among beef producers and veterinarians is largely unknown. This study
      compares the perceptions of beef producers and veterinarians on the burden of MAP
      infection in cow-calf herds and on measures to control new infections.
      Questionnaires were mailed to 989 US beef producers through state Designated
      Johne's Coordinators and to 1080 bovine veterinarians belonging to a US
      nationwide professional association. RESULTS: Twenty-two percent (34/155) of
      producers reported having infected animals in their herds. The mean (minimum,
      median, maximum) prevalence reported by producers was 0.8% (0, 0, 10). Twenty
      seven percent (27/100) of producers had at least one clinical animal during the
      previous year. Compared to the small herds (<50 head), the mean test-positive
      percentages and estimated prevalences were higher in medium (50-149) and highest
      in large (>=150) herds. Seedstock herds had a lower prevalence and these
      producers were more likely to enroll in Johne's disease (JD) control programs and
      test their herds. Veterinarians reported a mean overall animal level prevalence
      in their client herds of 5% (0, 2, 60). Similarly, 26% (0, 10, 100) of client
      herds had at least one infected animal. Mean percentage of infected cows within
      infected herds was 9% (0.01, 5, 80). Producers generally performed activities to
      control MAP transmission more frequently than perceived by veterinarians.
      Compared to veterinarians' opinions, producers were less likely to cull cows with
      signs consistent with JD (P < 0.01), but more likely to test purchased additions
      (P < 0.01). Testing recommendations by veterinarians (n = 277) for beef cow-calf
      herds were bacterial culture of feces (3%), PCR (14%), ELISA (35%) and a
      combination of these tests (47%). Seventy-nine percent of veterinarians
      recommended a 12-month interval between testing. CONCLUSIONS: Seedstock producers
      who had had JD risk assessments performed on their farms were more supportive of
      JD control programs and had a correspondingly lower prevalence. It is important
      to increase educational activities to provide relevant information to
      veterinarians and producers for better management and control of JD. Educational
      programs should target larger herds to maximize the impact.

PMID- 24456652
TI  - Clinical exome sequencing in daily practice: 1,000 patients and beyond.

PMID- 24456651
TI  - Autism spectrum disorder, flea and tick medication, and adjustments for exposure
      misclassification: the CHARGE (CHildhood Autism Risks from Genetics and
      Environment) case-control study.
AB  - BACKGROUND: The environmental contribution to autism spectrum disorders (ASD) is
      largely unknown, but household pesticides are receiving increased attention. We
      examined associations between ASD and maternally-reported use of imidacloprid, a
      common flea and tick treatment for pets. METHODS: Bayesian logistic models were
      used to estimate the association between ASD and imidacloprid and to correct for
      potential differential exposure misclassification due to recall in a case control
      study of ASD. RESULTS: Our analytic dataset included complete information for 262
      typically developing controls and 407 children with ASD. Compared with exposure
      among controls, the odds of prenatal imidacloprid exposure among children with
      ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval
      [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for
      exposures during pregnancy than for early life exposures, whereas limiting to
      frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9).
      CONCLUSIONS: Within plausible estimates of sensitivity and specificity, the
      association could result from exposure misclassification alone. The association
      between imidacloprid exposure and ASD warrants further investigation, and this
      work highlights the need for validation studies regarding prenatal exposures in
      ASD.

PMID- 24456653
TI  - Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic
      mice against intracerebral Escherichia coli K1 infection.
AB  - BACKGROUND: Prophylaxis with unmethylated cytosine phosphate guanidine (CpG)
      oligodeoxynucleotides (ODN) protects against several systemic experimental
      infections. Escherichia coli is a major cause of Gram-negative neonatal bacterial
      meningitis and also causes meningitis and meningoencephalitis in older and
      immunocompromised patients. METHODS: Wild-type (wt) and Toll-like receptor 9
      (TLR9)-deficient mice were rendered neutropenic by intraperitoneal administration
      of the anti-Ly-6G monoclonal antibody. Immunocompetent and neutropenic mice
      received intraperitoneal CpG ODN or vehicle 72 h prior to induction of E. coli K1
      meningoencephalitis. RESULTS: Pre-treatment with CpG ODN significantly increased
      survival of neutropenic wt mice from 33% to 75% (P = 0.0003) but did not protect
      neutropenic TLR9-/- mice. The protective effect of CpG ODN was associated with an
      enhanced production of interleukin (IL)-12/IL-23p40 with sustained increased
      levels in serum and spleen at least for 17 days after conditioning compared to
      buffer-treated animals. CpG-treated neutropenic wt mice showed reduced bacterial
      concentrations and increased recruitment of Ly6ChighCCR2+ monocytes in brain and
      spleen 42 h after infection. The levels of macrophage inflammatory protein 1alpha
      (MIP-1alpha) and interferon gamma (IFN-gamma) in spleen were higher 42 h after
      infection in CpG-treated compared to buffer-treated neutropenic animals. In
      immunocompetent mice, prophylaxis with CpG ODN did not significantly increase
      survival compared to the buffer group (60% vs. 45%, P = 0.2). CONCLUSIONS: These
      findings suggest that systemic administration of CpG ODN may help to prevent
      bacterial CNS infections in immunocompromised individuals.

PMID- 24456655
TI  - A new procedure to analyze the effect of air changes in building energy
      consumption.
AB  - BACKGROUND: Today, the International Energy Agency is working under good practice
      guides that integrate appropriate and cost effective technologies. In this paper
      a new procedure to define building energy consumption in accordance with the ISO
      13790 standard was performed and tested based on real data from a Spanish region.
      RESULTS: Results showed that the effect of air changes on building energy
      consumption can be defined using the Weibull peak function model. Furthermore,
      the effect of climate change on building energy consumption under several
      different air changes was nearly nil during the summer season. CONCLUSIONS: The
      procedure obtained could be the much sought-after solution to the problem stated
      by researchers in the past and future research works relating to this new
      methodology could help us define the optimal improvement in real buildings to
      reduce energy consumption, and its related carbon dioxide emissions, at minimal
      economical cost.

PMID- 24456654
TI  - The effect of a national quality improvement collaborative on prehospital care
      for acute myocardial infarction and stroke in England.
AB  - BACKGROUND: Previous studies have shown wide variations in prehospital ambulance
      care for acute myocardial infarction (AMI) and stroke. We aimed to evaluate the
      effectiveness of implementing a Quality Improvement Collaborative (QIC) for
      improving ambulance care for AMI and stroke. METHODS: We used an interrupted time
      series design to investigate the effect of a national QIC on change in delivery
      of care bundles for AMI (aspirin, glyceryl trinitrate [GTN], pain assessment and
      analgesia) and stroke (face-arm-speech test, blood pressure and blood glucose
      recording) in all English ambulance services between January 2010 and February
      2012. Key strategies for change included local quality improvement (QI) teams in
      each ambulance service supported by a national coordinating expert group that
      conducted workshops educating staff in QI methods to improve AMI and stroke care.
      Expertise and ideas were shared between QI teams who met together at three
      national workshops, between QI leads through monthly teleconferences, and between
      the expert group and participants. Feedback was provided to services using
      annotated control charts. RESULTS: We analyzed change over time using logistic
      regression with three predictor variables: time, gender, and age. There were
      statistically significant improvements in care bundles in nine (of 12)
      participating trusts for AMI (OR 1.04, 95% CI 1.04, 1.04), nine for stroke (OR
      1.06, 95% CI 1.05, 1.07), 11 for either AMI or stroke, and seven for both
      conditions. Overall care bundle performance for AMI increased in England from 43
      to 79% and for stroke from 83 to 96%. Successful services all introduced provider
      prompts and individualized or team feedback. Other determinants of success
      included engagement with front-line clinicians, feedback using annotated control
      charts, expert support, and shared learning between participants and
      organizations. CONCLUSIONS: This first national prehospital QIC led to
      significant improvements in ambulance care for AMI and stroke in England. The use
      of care bundles as measures, clinical engagement, application of quality
      improvement methods, provider prompts, individualized feedback and opportunities
      for learning and interaction within and across organizations helped the
      collaborative to achieve its aims.

PMID- 24456656
TI  - Evaluation of the accuracy of shoe fitting in older people using three
      dimensional foot scanning.
AB  - BACKGROUND: Ill-fitting footwear is a common problem in older people. The
      objective of this study was to determine the accuracy of shoe fitting in older
      people by comparing the dimensions of allocated shoes to foot dimensions obtained
      with a three-dimensional (3D) scanner. METHODS: The shoe sizes of 56 older people
      were determined with the Brannock device(r), and weightbearing foot scans were
      obtained with the FotoScan 3D scanner (Precision 3D Ltd, Weston-super-mare, UK).
      Participants were provided with a pair of shoes (Dr Comfort(r), Vista, CA, USA),
      available in three width fittings (medium, wide and extra wide). The dimensions
      (length, ball width and ball girth) of the allocated shoes were documented
      according to the last measurements provided by the manufacturer. Mean differences
      between last dimensions and foot dimensions obtained with the 3D scanner were
      calculated to provide an indication of shoe fitting accuracy. Participants were
      also asked to report their perception of shoe fit and comfort, using 100 mm
      visual analogue scales (VAS). RESULTS: Shoe size ranged from US size 7 to 14 for
      men and 5.5 to 11 for women. The allocated shoes were significantly longer than
      the foot (mean 23.6 mm, 95% confidence interval [CI] 22.1 to 25.2; t55 = 30.3, p
      < 0.001), however there were no significant differences in relation to ball width
      (mean 1.4 mm, 95% CI -0.1 to 2.9 mm; t55 = 1.9, p = 0.066) or ball girth (mean 
      0.7 mm, 95% CI -6.1 to 4.8 mm; t55 = -0.2, p = 0.810). Participants reported
      favourable perceptions of shoe fit (mean VAS = 90.7 mm, 95% CI 88.4 to 93.1 mm)
      and comfort (mean VAS = 88.4 mm, 95% CI 85.0 to 91.8 mm). CONCLUSION: Shoe size
      selection using the Brannock device(r) resulted in the allocation of shoes with
      last dimensions that were well matched to the dimensions of the foot.
      Participants also considered the shoes to be well fitted and comfortable. Older
      people with disabling foot pain can therefore be dispensed with appropriately
      fitted shoes using this technique, provided that the style and materials used are
      suitable and extra width fittings are available.

PMID- 24456657
TI  - Effect of pregestational diabetes mellitus on first trimester placental
      characteristics: three-dimensional placental volume and power Doppler indices.
AB  - OBJECTIVE: To investigate whether pregestational diabetes mellitus (DM) induces
      changes in vascular placental development detectable at first trimester. METHODS:
      This was a prospective case-control study in 69 women with pregestational DM and
      94 controls undergoing first-trimester combined screening for aneuploidies.
      Maternal characteristics, fetal nuchal translucency thickness, maternal serum
      pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic
      gonadotrophin (beta-hCG) were evaluated. Three-dimensional ultrasound was used to
      measure placental volume and three dimensional power Doppler (3D-PD) placental
      vascular indices including: vascularization index (VI), flow index (FI) and
      vascularization flow index (VFI). Pregnancy-associated hypertensive complications
      (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women
      and the group of diabetic women without PAHC were compared separately with the
      control group. RESULTS: 3D-PD placental vascular indexes were significantly lower
      in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04).
      These differences remained on excluding cases with PAHC in the DM group. No
      differences were found in placental volumes between the DM group and controls.
      Serum PAPP-A levels were also lower in diabetic women (p < 0.02) and negatively
      correlated with the degree of maternal metabolic control at first trimester.
      CONCLUSIONS: Pregestational DM induces demonstrable alterations in first
      trimester placental development, with significantly reduced placental
      vascularization indices and PAPP-A values. This effect is independent of the
      later development of PAHC.

PMID- 24456658
TI  - Effecting change in midwives' waterbirth practice behaviours on labour ward: an
      action research study.
AB  - INTRODUCTION: the use of water immersion for labour and birth has been shown to
      be beneficial for women in normal labour (Cluett et al, 2009). It was decided to
      use problem solving coordinator workshops to change in the way waterbirth
      practice was promoted and organised on labour ward. Findings from the first
      Action Research phase (Russell, 2011) led to the development of a waterbirth
      questionnaire to measure midwives' personal knowledge of waterbirth practice,
      waterbirth self-efficacy, social support and frequency of hydrotherapy and
      waterbirth practice. The aim of this paper is to share the questionnaire findings
      from an on-going action research study. METHOD: prior to the first workshop 62
      questionnaires were distributed to midwives (Bands 5, 6 and 7) working on labour
      ward. Subsequent questionnaires (n=53) were sent to Bands 5/6 midwives not
      involved in the workshops, at four (Group 2) and eight months (Group 3). N.B only
      Bands 5/6 midwives completed post workshop questionnaires. In total 169
      questionnaires were distributed. One-way ANOVA with Tukey post-hoc test and the
      chi(2) test were used to determine statistical significance. FINDINGS: 96
      questionnaires were returned (57%). Midwives' personal knowledge of waterbirth
      practice differed significantly between groups, (F2,85=3.67, p<0.05) with
      midwives in Group 1 giving significantly higher scores (X-=45.6, 95% CI [43.0,
      48.2]), than those in Group 3, (X-=41.7, 95% CI [40.0, 43.3]), p<0.05. Midwives'
      waterbirth self-efficacy did not differ significantly between groups (F2,88=3.15,
      p>0.05). However scores for social support did differ (F2,75=4.011, p=0.022),
      with midwives in Group 1 giving significantly lower scores (X-=8.0, 95% CI [6.4,
      9.5]) than those in Group 3 (X-=10.5, 95% CI [9.4, 11.6]), p=0.016. Fifty-five
      per cent of Group 1 midwives facilitated a waterbirth in the previous three
      months compared with 87% in Group 3. Changes in the frequency of waterbirth for
      these groups were statistically significant (x(2)=4.369, p<0.05, df=1).
      CONCLUSIONS: it appears that the co-ordinators were able to influence waterbirth
      practice because of changes in social support and frequency of waterbirth
      practice. Given the widespread and continued impact of the intervention, on
      midwives who attended workshops and those that did not, we feel it likely that a
      significant proportion of this change could be attributed to the introduction of
      problem solving waterbirth workshop. The findings from this study suggest that
      problem solving waterbirth workshops based on an action research format have the
      potential to normalise midwifery care within medically dominated hospital
      birthing environments.

PMID- 24456659
TI  - Narratives of distress about birth in South African public maternity settings: a
      qualitative study.
AB  - OBJECTIVE: to explore the factors associated with negative birth experiences in
      South African public maternity settings from the perspective of women's birth
      narratives. DESIGN: an explorative, qualitative research study using a narrative
      methodological framework and unstructured interviewing. SETTING: the city of Cape
      Town in South Africa. PARTICIPANTS: 33 low-income women aged 18-42 years who had
      recently given birth to an infant in the public maternity sector. FINDINGS: more
      than half of the women (n=18) narrated 'narratives of distress' in relation to
      their birth experiences. One third narrated 'good' birth experiences and four
      women told minimalistic or neutral birth narratives. This paper reports only on
      factors associated with women's distress narratives. Narratives of distress were
      associated with poor quality of intrapartum care and characterised by the
      following four themes, namely (1) negative interpersonal relations with
      caregivers, (2) lack of information, (3) neglect and abandonment and (4) the
      absence of a labour companion. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      poor relationships with caregivers emerged as central to women's distress
      narratives. Interventions aimed at improving interpersonal communication,
      connection and rapport between caregivers and labouring women are central to
      improving quality of care in resource-constrained settings.

PMID- 24456660
TI  - Bioactive phthalides from Ligusticum sinense Oliv cv. Chaxiong.
AB  - Five new phthalides (1-4, 6), two new natural products (5, 7) and five known
      phthalides (8-12) were isolated from the aerial parts of Ligusticum sinense Oliv
      cv. Chaxiong. Their structures were elucidated by HR-ESI-MS, UV, IR, 1D and 2D
      NMR (HSQC, HMBC, (1)H-(1)H COSY, NOESY) methods. The absolute configurations were
      established by the circular dichroism (CD) spectrum and the modified Mosher's
      method. Compounds 1-8 were tested against SK-N-SH cell depriving oxygen and
      glucose and showed different degrees of increasing the cell survival, among which
      compounds 1, 4 and 8 (10 MUM) showed higher cell survival than Ginsenoside Rg1.

PMID- 24456661
TI  - Inbreeding effects on standard metabolic rate investigated at cold, benign and
      hot temperatures in Drosophila melanogaster.
AB  - Inbreeding increases homozygosity, which is known to affect the mean and variance
      of fitness components such as growth, fecundity and mortality rate. Across inbred
      lines inbreeding depression is typically observed and the variance between lines
      is increased in inbred compared to outbred lines. It has been suggested that
      damage incurred from increased homozygosity entails energetic cost associated
      with cellular repair. However, little is known about the effects of inbreeding on
      standard metabolic rate. Using stop-flow respirometry we performed repeated
      measurements of metabolic rate in replicated lines of inbred and outbred
      Drosophila melanogaster at stressful low, benign and stressful high temperatures.
      The lowest measurements of metabolic rate in our study are always associated with
      the low activity period of the diurnal cycle and these measurements therefore
      serve as good estimates of standard metabolic rate. Due to the potentially added
      costs of genetic stress in inbred lines we hypothesized that inbred individuals
      have increased metabolic rate compared to outbred controls and that this is more
      pronounced at stressful temperatures due to synergistic inbreeding by environment
      interactions. Contrary to our hypothesis we found no significant difference in
      metabolic rate between inbred and outbred lines and no interaction between
      inbreeding and temperature. Inbreeding however effected the variance; the
      variance in metabolic rate was higher between the inbred lines compared to the
      outbred control lines with some inbred lines having very high or low standard
      metabolic rate. Thus genetic drift and not inbreeding per se seem to explain
      variation in metabolic rate in populations of different size. 

PMID- 24456663
TI  - A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3)
      long chain PUFA status in plasma phospholipids in humans.
AB  - This study aimed to determine the effect of reducing the dietary linoleic acid
      (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status
      in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks.
      Nutrient intakes were estimated from diet diaries and blood samples were
      collected for assessment of fatty acid composition in plasma and erythrocyte
      phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA
      intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6
      PUFA content of plasma and erythrocyte phospholipids were significantly reduced
      after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma
      phospholipids was significantly increased after the low LA diet compared to
      baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA
      intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of
      increased n-3 LCPUFA intake. 

PMID- 24456662
TI  - Arsenic and fluoride co-exposure affects the expression of apoptotic and
      inflammatory genes and proteins in mononuclear cells from children.
AB  - Humans may be exposed to arsenic (As) and fluoride (F) through water consumption.
      However, the interaction between these two elements and gene expression in
      apoptosis or inflammatory processes in children has not been thoroughly
      investigated. Herein, the expression of cIAP-1, XIAP, TNF-alpha, ENA-78,
      survivin, CD25, and CD40 was evaluated by RT-PCR. Additionally, the surface
      expression of CD25, CD40, and CD40L on peripheral blood mononuclear cells was
      analyzed by flow cytometry, and TNF-alpha was measured by Western blotting. This
      study examined 72 children aged 6-12 years who were chronically exposed to As
      (154.2MUg/L) and F (5.3mg/L) in drinking water and in food cooked with the same
      water. The urine concentrations of As (6.9-122.4MUg/L) were positively correlated
      with the urine concentrations of F (1.0-8.8mg/L) (r(2)=0.413, p<0.0001). The CD25
      gene expression levels and urine concentrations of As and F were negatively
      correlated, though the CD40 expression levels were negatively correlated only
      with the As concentration. Age and height influenced the expression of cIAP-1,
      whereas XIAP expression was correlated only with age. Additionally, there was a
      lower percentage of CD25- and CD40-positive cells in the group of 6- to 8-year
      old children exposed to the highest concentrations of both As and F when compared
      to the 9- to 12-year-old group (CD25: 0.7+/-0.8 vs. 1.1+/-0.9, p<0.0014; CD40:
      16.0+/-7.0 vs. 21.8+/-5.8, p<0.0003). PHA-stimulated lymphocytes did not show any
      changes in the induction of CD25, CD69, or CD95. In summary, high concentrations
      of As and F alter the expression patterns of CD25 and CD40 at both the genetic
      and protein levels. These changes could decrease immune responses in children
      exposed to As and F.

PMID- 24456664
TI  - miR-99a promotes proliferation targeting FGFR3 in human epithelial ovarian cancer
      cells.
AB  - MiRNAs have been reported as important regulators in normal physiological
      processes, human cancer, and even their roles as therapeutic targets have been
      proposed. In epithelial ovarian cancer (EOC), the expression of miRNAs is
      reported to remarkably deregulate, showing that miRNAs are involved in the
      initiation and progression of this disease. In this study, we found that miR-99a
      was obviously decreased in EOC tissues, serums and cell lines SKOV-3.
      Importantly, fibroblast growth factor receptor 3 (FGFR3), predicted to be one
      target gene of miR-99a using computational algorithms, was higher in expression
      in EOC cells. Subsequently, FGFR3 was proved to be direct target of miR-99a by
      dual luciferase assay. Furthermore, overexpression of miR-99a dramatically
      suppressed expression level of FGFR3 at both mRNA and protein levels, proving
      FGFR3 to be inversely correlated with miR-99a. Finally, overexpression of miR-99a
      could significantly inhibit EOC cell proliferation in vitro by decreasing the
      expression of FGFR3 which also reduced the EOC cell growth after siRNA knockdown.
      Conclusively, miR-99a expression was remarkably downregulated in serums, tissues
      and cell and suppresses EOC cell proliferation by targeting FGFR3, suggesting miR
      99a as a prospective prognosis marker and potential tumor suppressor for EOC
      therapeutics. 

PMID- 24456665
TI  - Automatic construction of an anatomical coordinate system for three-dimensional
      bone models of the lower extremities--pelvis, femur, and tibia.
AB  - Automated methods for constructing patient-specific anatomical coordinate systems
      (ACSs) for the pelvis, femur and tibia were developed based on the bony geometry
      of each, derived from computed tomography (CT). The methods used principal axes
      of inertia, principal component analysis (PCA), cross-sectional area, and
      spherical and ellipsoidal surface fitting to eliminate the influence of rater's
      bias on reference landmark selection. Automatic ACSs for the pelvis, femur, and
      tibia were successfully constructed on each 3D bone model using the developed
      algorithm. All constructions were performed within 30s; furthermore, between- and
      within- rater errors were zero for a given CT-based 3D bone model, owing to the
      automated nature of the algorithm. ACSs recommended by the International Society
      of Biomechanics (ISB) were compared with the automatically constructed ACS, to
      evaluate the potential differences caused by the selection of the coordinate
      system. The pelvis ACSs constructed using the ISB-recommended system were tilted
      significantly more anteriorly than those constructed automatically (range, 9.6
      18.8 degrees ). There were no significant differences between the two methods for
      the femur. For the tibia, significant differences were found in the direction of
      the anteroposterior axis; the anteroposterior axes identified by ISB were more
      external than those in the automatic ACS (range, 17.5-25.0 degrees ). 

PMID- 24456666
TI  - "Skip the infection, get the injection": a case study in emergency preparedness
      education.
AB  - The frequency of natural and manmade disasters along with increasing potential
      for public health emergencies emphasizes the need for emergency preparedness
      education. Because nurses are the largest group of health professionals to meet
      the needs of those affected by disasters and public health emergencies, schools
      of nursing need to prepare graduates who are knowledgeable about disaster and
      public health emergency management. The use of core competencies may be a means
      to ensure consistent application of best practices in disaster health care. The
      next step in competency development involves validation through evidence. Through
      documentation and dissemination of their experiences with emergency preparedness
      education, schools of nursing can provide supportive evidence to aid in
      competency development. The purpose of this paper is present a case study of an
      ongoing and evolving public health nursing education project consistent with
      disaster health care and emergency preparedness competencies. 

PMID- 24456667
TI  - Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1.
AB  - INTRODUCTION: Defects in the DNA mismatch repair (MMR) protein MLH1 are
      frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected
      tumors generate much less metastatic potential than the MLH1 proficient forms.
      Although MLH1 has been shown to be not only involved in postreplicative MMR but
      also in several MMR independent processes like cytoskeletal organization, the
      connection between MLH1 and metastasis remains unclear. We recently identified
      non-erythroid spectrin alphaII (SPTAN1), a scaffolding protein involved in cell
      adhesion and motility, to interact with MLH1. In the current study, the
      interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis
      was evaluated. METHODS: Nine cancer cell lines as well as fresh and paraffin
      embedded colon cancer tissue from 12 patients were used in gene expression
      studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by
      siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo
      cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and
      MLH1 deficient HEK293T compared to their MLH1 proficient sister cells,
      respectively. RESULTS: MLH1 deficiency is clearly associated with SPTAN1
      reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1
      in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co
      expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient
      HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1
      proficient sister clones. Consequently, overexpression of SPTAN1 increased
      migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular
      mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability.
      CONCLUSIONS: These data suggest that SPTAN1 levels decreased in concordance with
      MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer
      cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.

PMID- 24456668
TI  - Alcohol assessment & feedback by e-mail for university student hazardous and
      harmful drinkers: study protocol for the AMADEUS-2 randomised controlled trial.
AB  - BACKGROUND: Alcohol is responsible for a large and growing proportion of the
      global burden of disease, as well as being the cause of social problems. Brief
      interventions are one component of comprehensive policy measures necessary to
      reduce these harms. Brief interventions increasingly take advantage of the
      Internet to reach large numbers of high risk groups such as students. The
      research literature on the efficacy and effectiveness of online interventions is
      developing rapidly. Although many studies show benefits in the form of reduced
      consumption, other intervention studies show no effects, for reasons that are
      unclear. Sweden became the first country in the world to implement a national
      system in which all university students are offered a brief online intervention
      via an e-mail. METHODS/DESIGN: This randomized controlled trial (RCT) aims to
      evaluate the effectiveness of this national system comprising a brief online
      intervention among university students who are hazardous and harmful drinkers.
      This study employs a conventional RCT design in which screening to determine
      eligibility precedes random allocation to immediate or delayed access to online
      intervention. The online intervention evaluated comprises three main components;
      assessment, normative feedback and advice on reducing drinking. Screening is
      confined to a single question in order to minimise assessment reactivity and to
      prevent contamination. Outcomes will be evaluated after 2 months, with total
      weekly alcohol consumption being the primary outcome measure. Invitations to
      participate are provided by e-mail to approximately 55,000 students in 9 Swedish
      universities. DISCUSSION: This RCT evaluates routine service provision in Swedish
      universities via a delay in offer of intervention to the control group. It
      evaluates effects in the key population for whom this intervention has been
      designed. Study findings will inform the further development of the national
      service provision. TRIAL REGISTRATION: ISRCTN02335307.

PMID- 24456669
TI  - Vaginal tolerance of CT based image-guided high-dose rate interstitial
      brachytherapy for gynecological malignancies.
AB  - BACKGROUND: Purpose of this study was to identify predictors of vaginal ulcer
      after CT based three-dimensional image-guided high-dose-rate interstitial
      brachytherapy (HDR-ISBT) for gynecologic malignancies. METHODS: Records were
      reviewed for 44 female (14 with primary disease and 30 with recurrence) with
      gynecological malignancies treated with HDR-ISBT with or without external beam
      radiation therapy. The HDR-ISBT applicator insertion was performed with image
      guidance by trans-rectal ultrasound and CT. RESULTS: The median clinical target
      volume was 35.5 ml (2.4-142.1 ml) and the median delivered dose in equivalent
      dose in 2 Gy fractions (EQD2) for target volume D90 was 67.7 Gy (48.8-94.2 Gy,
      doses of external-beam radiation therapy and brachytherapy were combined). For re
      irradiation patients, median EQD2 of D(2cc) for rectum and bladder, D0.5cc,
      D(1cc), D(2cc), D(4cc), D(6cc) and D(8cc) for vaginal wall was 91.1 Gy, 100.9 Gy,
      260.3 Gy, 212.3 Gy, 170.1 Gy, 117.1 Gy, 105.2 Gy, and 94.7 Gy, respectively. For
      those without prior radiation therapy, median EQD2 of D(2cc) for rectum and
      bladder, D(0.5cc), D(1cc), D(2cc), D(4cc), D(6cc) and D(8cc) for vaginal wall was
      56.3 Gy, 54.3 Gy, 147.4 Gy, 126.2 Gy, 108.0 Gy, 103.5 Gy, 94.7 Gy, and 80.7 Gy,
      respectively. Among five patients with vaginal ulcer, three had prior pelvic
      radiation therapy in their initial treatment and three consequently suffered from
      fistula formation. On univariate analysis, re-irradiation and vaginal wall D(2cc)
      in EQD2 was the clinical predictors of vaginal ulcer (p = 0.035 and p = 0.025,
      respectively). The ROC analysis revealed that vaginal wall D(2cc) is the best
      predictor of vaginal ulcer. The 2-year incidence rates of vaginal ulcer in the
      patients with vaginal wall D(2cc) in EQD2 equal to or less than 145 Gy and over
      145 Gy were 3.7% and 23.5%, respectively, with a statistically significant
      difference (p = 0.026). CONCLUSIONS: Re-irradiation and vaginal D(2cc) is a
      significant predictor of vaginal ulcer after HDR-ISBT for gynecologic
      malignancies. Three-dimensional image-guided treatment planning should be
      performed to ensure adequate target coverage while minimizing vaginal D(2cc) in
      order to avoid vagina ulcer.

PMID- 24456670
TI  - Role of general practice in the utilisation of the NSW Get Healthy Information
      and Coaching Service.
AB  - A lifestyle-modification telephone-based service is delivered in New South Wales
      (NSW; the Get Healthy Information and Coaching Service (GHS)) as an important
      obesity-prevention, population-wide program. The present study examined referrals
      from general practitioners (GP) versus self-referral to the GHS in terms of risk
      profile and effectiveness of outcomes. The study used a pre-post test design to
      assess changes in outcomes within the setting of a telephone-based lifestyle
      support service available to NSW adults (18+ years) who self-referred or were
      referred by their health practitioner and/or GP, and registered for the GHS
      between February 2009 and August 2013 (n = 22 183). The GHS has two service
      components: (1) the provision of an information kit (one off contact) on healthy
      eating, being physically active and achieving and/or maintaining a healthy
      weight; and (2) a 6-month coaching program that includes 10 telephone calls aimed
      at achieving and maintaining lifestyle-related goals. Sociodemographic
      characteristics, referral source and self-reported anthropometric (height, waist
      and waist circumference (WC)) and behavioural risk factor (physical activity and
      nutrition-related behaviours) data were collected at baseline and at 6 months.
      Analysis revealed that GPs effectively recruited hard-to-reach subtargets, as
      well as adults who are obese and have an increased WC risk. Participants in the
      GHS coaching program, irrespective of GHS referral source, reported a mean weight
      loss of -3.8 kg, a decrease in WC of -5.0 cm and increases in both fruit and
      vegetable consumption and physical activity. In conclusion, GPs have an important
      role in GHS uptake (through proactive referral or as an adjunct to practice-based
      interventions) because they can recruit those most at need and facilitate
      improvements in their patients' risk factor profiles.

PMID- 24456671
TI  - Development and evaluation of a tacrolimus cream formulation using a binary
      solvent system.
AB  - We developed an oil/water-type tacrolimus (FK506) cream formulation as an
      alternative to Protopic ointment for atopic dermatitis treatment. We determined
      the effects of solvents used in topical preparations on FK506 solubility and
      stability, and evaluated FK506 transdermal absorption into rat skin from
      solutions, emulsions, and creams. Screening indicated that diethyl sebacate
      (DES), isopropyl myristate (IPM), propylene glycol (PG), and oleyl alcohol (OA)
      were adequate FK506 solvents. When FK506 solutions prepared using these solvents
      were transdermally administered, AUC0-24 values for DES and IPM were higher than
      or similar to that for 0.1% Protopic ointment. The AUC0-24 values for PG and OA
      were low, so these solvents did not enhance absorption. The residual ratios of
      FK506 in DES and IPM solutions after incubation at 70 degrees C for 9d were 95.6%
      and 88.6%, respectively, so DES and IPM were chosen for emulsion preparation.
      When the emulsions were transdermally administered, the IPM emulsion AUC0-24
      values increased 4.6-fold; DES emulsions did not show high transdermal
      absorption, but showed sustained characteristics. A cream formulation prepared by
      mixture of IPM and DES also showed high absorption and transdermal absorption
      increased with increasing IPM ratio. We developed an FK506 cream formulation with
      a controllable transdermal absorption rate by manipulating the IPM:DES ratio.

PMID- 24456672
TI  - Solid dispersion of berberine-phospholipid complex/TPGS 1000/SiO2: preparation,
      characterization and in vivo studies.
AB  - Berberine (Ber), an isoquinoline alkaloid, arouses wide interests in many
      researchers in recent years because of its numerous new pharmacological actions.
      However Ber's low oral bioavailability restricts its wide application. In this
      study, a solid dispersion (BPTS-SD) composed of berberine-phospholipid complex
      (BPC), D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS 1000) and SiO2
      was prepared by simple solvent evaporation technique. BPC was employed to improve
      the liposolubility of Ber, and SiO2 was used to improve the flowability of BPTS
      SD, while TPGS 1000 played a dual role: firstly, as a solid dispersion carrier to
      improve the dissolution rate of BPC and secondly, as a P-glycoprotein (P-gp)
      inhibitor to enhance the intestinal absorption of Ber. FTIR, DSC and SEM analysis
      proved the formation of BPC and BPTS-SD. Po/w of BPC successfully increased from
      0.25 to 8.75. In vitro dissolution study showed that the cumulative dissolution
      percentages of BPTS-SDs were nearly 2.67-4.78-folds of BPC. Single-pass
      intestinal perfusion studies showed that the absorption of Ber in BPC was
      increased nearly 1.4-2.0-folds compared to that of Ber which was mainly due to
      the improved liposolubility, and further increased by BPTS-SD around 0.1-1.3
      folds compared to that of BPC through the P-gp inhibition of TPGS 1000.
      Significant improvements in Cmax and AUC0->t of BPC and BPTS-SD were obtained in
      pharmacokinetic study (the highest improvement in oral relative bioavailability
      of BPTS-SD-1 was 322.66% of Ber). All these results indicated that BPTS-SD can be
      a promising drug delivery system to improve their oral bioavailability for the
      Ber's analogues. In particular this solid dispersion can be prepared just by a
      simple method and has a strong feasibility for industrialization.

PMID- 24456673
TI  - A non-binary biopharmaceutical classification of drugs: the ABGamma system.
AB  - The purpose of the present work is to develop a non-binary biopharmaceutical
      classification system the so called ABGamma system. The original mathematical
      model used for the development of BCS, appropriately modified, was applied to
      estimate the limiting values of drug solubility and permeability when the
      fraction of dose absorbed, Fa, was 0.90 or 0.20. The ABGamma system is based on
      the fraction of dose absorbed and relies on permeability, solubility plane. The
      first category (A, alpha) includes drugs with Fa >= 0.90, whereas the B (beta)
      category consists of drugs with Fa <= 0.20. The area lying between the two
      boundaries of A and B defines the third category (gamma), Gamma, (0.20<Fa<0.90).
      For comparative purposes, the BCS classes I-IV were co-plotted together with the
      ABGamma system. Most of the BCS classes II and III are included in category Gamma
      which mainly consists of drugs with properties like moderate or low solubility
      and permeability. Due to the dynamic character of dissolution and uptake
      processes, category A is expanded toward BCS Class II. The ABGamma system allows
      the classification of all compounds into three categories (A, B, Gamma) in terms
      of the fraction of dose absorbed.

PMID- 24456674
TI  - In vitro dissolution enhancement of micronized l-nimodipine by antisolvent re
      crystallization from its crystal form H.
AB  - In order to enhance solubility and dissolution rate in water, micronized l
      nimodipine (NMD) has been successfully prepared by antisolvent re-crystallization
      process using acetone as solvent and deionized water as antisolvent. The effects
      of five experimental parameters on the mean particle size (MPS) of NMD
      nanosuspension were investigated. It was found that the MPS of NMD nanosuspension
      decreased significantly when the concentration of NMD-acetone solution increased
      from 50 to 150 mg/mL along with the increase of volume ratio of antisolvent to
      solvent from 1 to 3, and then increased slightly with the following increase of
      them. By contrast, the MPS decreased with the increased feed rate of NMD-acetone
      solution and the amount of surfactant, from 1 to 3 mL/min and 0.025% to 0.2%,
      respectively. Thereafter, the MPS did not show any obvious change. The
      precipitation temperature had no significant effects on MPS. The optimum
      micronization conditions were determined as follows: NMD-acetone solution
      concentration of 150 mg/mL, the volume ratio of antisolvent to solvent of 3, the
      flow rate of NMD-acetone solution of 9 mL/min, the preparation temperature of 15
      degrees C and the amount of the surfactant of 0.2%. Under optimum conditions,
      micronized NMD with a MPS of 708.3 nm was obtained. The micronized product was
      characterized using scanning electron microscopy (SEM), Fourier transform
      infrared spectroscopy (FTIR), high performance liquid chromatography-mass
      spectrometry (LC-MS), X-ray diffraction (XRD), differential scanning calorimetry
      (DSC), and thermo gravimetric (TG), to verify the influences of micronization
      process on the final product. The results showed that the chemical structure of
      micronized NMD was not changed, but the crystalline structure had undergone
      transition during precipitation, which changed from form H into L. The
      dissolution test showed that micronized NMD exhibited enhanced dissolution rate
      and solubility of 5.22 folds compared to raw H-NMD. These results suggested that
      micronized NMD may have potential value to become a new oral NMD formulation with
      high bioavailability.

PMID- 24456676
TI  - Evaluation of multivariate linear regression and artificial neural networks in
      prediction of water quality parameters.
AB  - This paper examined the efficiency of multivariate linear regression (MLR) and
      artificial neural network (ANN) models in prediction of two major water quality
      parameters in a wastewater treatment plant. Biochemical oxygen demand (BOD) and
      chemical oxygen demand (COD) as well as indirect indicators of organic matters
      are representative parameters for sewer water quality. Performance of the ANN
      models was evaluated using coefficient of correlation (r), root mean square error
      (RMSE) and bias values. The computed values of BOD and COD by model, ANN method
      and regression analysis were in close agreement with their respective measured
      values. Results showed that the ANN performance model was better than the MLR
      model. Comparative indices of the optimized ANN with input values of temperature
      (T), pH, total suspended solid (TSS) and total suspended (TS) for prediction of
      BOD was RMSE = 25.1 mg/L, r = 0.83 and for prediction of COD was RMSE = 49.4
      mg/L, r = 0.81. It was found that the ANN model could be employed successfully in
      estimating the BOD and COD in the inlet of wastewater biochemical treatment
      plants. Moreover, sensitive examination results showed that pH parameter have
      more effect on BOD and COD predicting to another parameters. Also, both
      implemented models have predicted BOD better than COD. 

PMID- 24456675
TI  - A model to determine the effect of collagen fiber alignment on heart function
      post myocardial infarction.
AB  - BACKGROUND: Adverse remodeling of the left ventricle (LV) following myocardial
      infarction (MI) leads to heart failure. Recent studies have shown that scar
      anisotropy is a determinant of cardiac function post-MI, however it remains
      unclear how changes in extracellular matrix (ECM) organization and structure
      contribute to changes in LV function. The objective of this study is to develop a
      model to identify potential mechanisms by which collagen structure and
      organization affect LV function post-MI. METHODS: A four-region, multi-scale,
      cylindrical model of the post-MI LV was developed. The mechanical properties of
      the infarct region are governed by a constitutive equation based on the
      uncrimping of collagen fibers. The parameters of this constitutive equation
      include collagen orientation, angular dispersion, fiber stiffness, crimp angle,
      and density. Parametric variation of these parameters was used to elucidate the
      relationship between collagen properties and LV function. RESULTS: The
      mathematical model of the LV revealed several factors that influenced cardiac
      function post-MI. LV function was maximized when collagen fibers were aligned
      longitudinally. Increased collagen density was also found to improve stroke
      volume for longitudinal alignments while increased fiber stiffness decreased
      stroke volume for circumferential alignments. CONCLUSIONS: The results suggest
      that cardiac function post-MI is best preserved through increased circumferential
      compliance. Further, this study identifies several collagen fiber-level
      mechanisms that could potentially regulate both infarct level and organ level
      mechanics. Improved understanding of the multi-scale relationships between the
      ECM and LV function will be beneficial in the design of new diagnostic and
      therapeutic technologies.

PMID- 24456677
TI  - Effect of the degree of reverse Trendelenburg position on intraocular pressure
      during prone spine surgery: a randomized controlled trial.
AB  - BACKGROUND CONTEXT: Postoperative vision loss complicates an estimated 1 in 1,100
      prone spine surgical cases. This complication has been attributed to ischemic
      optic neuropathy, with one proposed reason being perioperative elevations in
      intraocular pressure (IOP). Previous research has studied the effects of table
      inclination on IOP in awake volunteers; however, the effects in spine surgery
      patients have not been investigated for reverse Trendelenburg positioning using a
      prospective, randomized controlled study design. PURPOSE: To assess the effect of
      table inclination on IOP in patients undergoing prone spine surgery. STUDY
      DESIGN: Single-center, prospective randomized controlled study. PATIENT SAMPLE:
      Nineteen patients with no history of eye pathology, undergoing prone spine
      surgery at Dwight D. Eisenhower Army Medical Center, were randomly assigned to a
      table position: neutral, 5 degrees , or 10 degrees  of reverse Trendelenburg.
      OUTCOME MEASURES: Intraocular pressure, mean arterial pressure (MAP), estimated
      blood loss, fluid resuscitation, and ophthalmologic complication were assessed
      before and after induction and at incremental times during surgery, beginning at
      30 minutes, 60 minutes, and 60-minute increments thereafter. METHODS:
      Multivariate analyses evaluated surgical time, IOP, MAP, estimated blood loss,
      and fluid resuscitation as a function of table inclination to determine the
      effect of patient positioning on identified risk factors for postoperative vision
      loss. RESULTS: Surgical times ranged from 33 to 325 minutes. A rapid increase in
      IOP was noted after prone positioning, with continued increases as time elapsed.
      The neutral group exhibited statistically higher IOP compared with the 5 degrees 
      reverse Trendelenburg group after 60 minutes and the 10 degrees  group through 60
      minutes of surgery. The trend continued through 120 minutes; however, because of
      a lack of power, we were unable to determine the statistical significance. There
      were no statistically significant differences between the 5 degrees  and 10
      degrees  reverse Trendelenburg groups. CONCLUSIONS: Reverse Trendelenburg
      positioning elicits decreased IOP compared with prone positioning for surgery
      times less than 120 minutes. Ten degrees of reverse Trendelenburg attenuate the
      rise in IOP during prone spine surgery superiorly in comparison with 5 degrees .
      No significant complications were associated with reverse Trendelenburg
      positioning.

PMID- 24456678
TI  - Predicting surgical site infection after spine surgery: a validated model using a
      prospective surgical registry.
AB  - BACKGROUND CONTEXT: The impact of surgical site infection (SSI) is substantial.
      Although previous study has determined relative risk and odds ratio (OR) values
      to quantify risk factors, these values may be difficult to translate to the
      patient during counseling of surgical options. Ideally, a model that predicts
      absolute risk of SSI, rather than relative risk or OR values, would greatly
      enhance the discussion of safety of spine surgery. To date, there is no risk
      stratification model that specifically predicts the risk of medical complication.
      PURPOSE: The purpose of this study was to create and validate a predictive model
      for the risk of SSI after spine surgery. STUDY DESIGN: This study performs a
      multivariate analysis of SSI after spine surgery using a large prospective
      surgical registry. Using the results of this analysis, this study will then
      create and validate a predictive model for SSI after spine surgery. PATIENT
      SAMPLE: The patient sample is from a high-quality surgical registry from our two
      institutions with prospectively collected, detailed demographic, comorbidity, and
      complication data. OUTCOME MEASURES: An SSI that required return to the operating
      room for surgical debridement. MATERIALS AND METHODS: Using a prospectively
      collected surgical registry of more than 1,532 patients with extensive
      demographic, comorbidity, surgical, and complication details recorded for 2 years
      after the surgery, we identified several risk factors for SSI after multivariate
      analysis. Using the beta coefficients from those regression analyses, we created
      a model to predict the occurrence of SSI after spine surgery. We split our data
      into two subsets for internal and cross-validation of our model. We created a
      predictive model based on our beta coefficients from our multivariate analysis.
      RESULTS: The final predictive model for SSI had a receiver-operator curve
      characteristic of 0.72, considered to be a fair measure. The final model has been
      uploaded for use on SpineSage.com. CONCLUSIONS: We present a validated model for
      predicting SSI after spine surgery. The value in this model is that it gives the
      user an absolute percent likelihood of SSI after spine surgery based on the
      patient's comorbidity profile and invasiveness of surgery. Patients are far more
      likely to understand an absolute percentage, rather than relative risk and
      confidence interval values. A model such as this is of paramount importance in
      counseling patients and enhancing the safety of spine surgery. In addition, a
      tool such as this can be of great use particularly as health care trends toward
      pay for performance, quality metrics (such as SSI), and risk adjustment. To
      facilitate the use of this model, we have created a Web site (SpineSage.com)
      where users can enter patient data to determine likelihood for SSI.

PMID- 24456679
TI  - The continuum of disability over the lifespan: the convergence of aging with
      disability and aging into disability.

PMID- 24456680
TI  - Life course health and socioeconomic profiles of Americans aging with disability.
AB  - BACKGROUND: While cross-sectional data have been invaluable for describing
      national trends in disability over time, we know comparatively little, at a
      population level, about the long term experiences of persons living with a
      disability over the adult life course. OBJECTIVE: In this paper we use nationally
      representative data from the U.S. Panel Study of Income Dynamics to describe the
      life course health and socioeconomic profiles of Americans who are aging with a
      work-limiting disability. METHODS: Data come from a cohort of adults age 20-34 in
      1979, who were followed annually for 30 years to 2009 (to age 50-64). Disability
      is defined according to repeated measures of work limitations in prime working
      years. Using growth curve models we describe the life course profile of these
      Americans aging with work-limiting disability with respect to health, educational
      attainment, family formation, economic fortunes, and occupational history, and
      compare them to those who have not experienced repeated work-limiting disability
      in adulthood. RESULTS: Persons with persistent work-limiting disability prior to
      age 50 experienced lower rates of employment and lower household incomes over
      adulthood in comparison to those aging without a work-limiting disability.
      Additionally, in the mid-life period, adults with work-limiting disabilities were
      more likely to practice poor health behaviors (reflected by smoking, obesity, and
      sedentary activity) and to experience restrictions in functional independence
      than those without a work-limiting disability. CONCLUSIONS: Our findings suggest
      that there are critical risk factors that make adults aging with work-limiting
      disability more vulnerable with respect to their health and independence as they
      age, suggesting avenues for intervention that may equalize the health and
      independence of Americans aging with and aging into disability in the years
      ahead.

PMID- 24456681
TI  - Interventions to promote health: crossing networks of intellectual and
      developmental disabilities and aging.
AB  - BACKGROUND: People with intellectual and developmental disabilities experience
      lower levels of healthy behaviors as do older persons, making health promotion a
      key priority for these populations. OBJECTIVE: The aim of this paper is to review
      the two fields of developmental disability and aging health promotion research in
      order to understand strategies used by both and to identify emerging and
      innovative practices that disability researchers can learn from each other.
      METHODS: We conducted scoping reviews of health promotion intervention peer
      reviewed articles in English from 1991 to 2011 for intellectual and developmental
      disabilities and from 2007 to 2011 for the more extensive gerontological
      literature. Two reviewers extracted data. RESULTS: The disability review
      identified 34 studies and three main types of interventions: exercise, multi
      component, and health screens. The aging review identified 176 articles which had
      a wider variety of intervention topics and techniques, with more articles
      including innovative approaches to bringing interventions to community settings
      across a wider variety of populations. CONCLUSIONS: As people with intellectual
      and developmental disabilities are living longer, disability health promotion can
      look to the aging literature for ideas to incorporate in future interventions for
      people with intellectual and developmental disabilities, while the gerontological
      research can learn from the research in intellectual and developmental
      disabilities on ways to adapt health promotion interventions to people with
      cognitive and physical limitations. Use of universal design principles could
      enable greater inclusion of people with disabilities in health promotion
      interventions for the general aging population.

PMID- 24456682
TI  - The potential for technology to enhance independence for those aging with a
      disability.
AB  - Technologies of all kinds can sustain and accelerate improvements in health and
      quality of life for an aging population, and enhance the independence of persons
      with disabilities. Assistive technologies are widely used to promote independent
      functioning, but the aging of users and their devices produces unique challenges
      to individuals, their families, and the health care system. The emergence of new
      "smart" technologies that integrate information technology with assistive
      technologies has opened a portal to the development of increasingly powerful,
      individualized tools to assist individuals with disabilities to meet their needs.
      Yet, issues of access and usability remain to be solved for their usefulness to
      be fully realized. New cohorts aging with disabilities will have more resources
      and more experience with integrated technologies than current elders. Attention
      to technological solutions that help them adapt to the challenges of later life
      is needed to improve quality of life for those living long lives with
      disabilities. 

PMID- 24456683
TI  - Trends in disability and related chronic conditions among the forty-and-over
      population: 1997-2010.
AB  - BACKGROUND: Downward trends in activity limitations among the older U.S.
      population have recently plateaued, while activity limitation among the pre
      retirement population has increased. OBJECTIVES: Update temporal trends in
      limitations in sensory and physical functions, instrumental activities of daily
      living (IADLs), and activities of daily living (ADLs) for the 40-64 and 65-and
      over U.S. populations; assess the extent to which trends in education, smoking,
      and obesity could account for the trends in limitations; and examine trends in
      conditions cited as causes of limitations, their durations, and proportion of
      life spent with them. METHODS: Multivariate analysis of the 1997-2010 National
      Health Interview Survey. RESULTS: For the younger group, there have been
      increases in all limitations, except trouble hearing, which has declined.
      Increased obesity could account for the increases in vision, physical function,
      and IADL limitations. Musculoskeletal conditions, such as arthritis and back/neck
      problems, are frequently cited as causes of limitation, and there are growing
      roles for depression and nervous system conditions. For the 65-and-over group,
      there have been decreases in all limitations, except difficulty with physical
      functions, which is up. Increased education could account for the decline in ADL
      limitation, and increased obesity could account for increased difficulty with
      physical functions. Musculoskeletal conditions are also frequently cited as
      causes of limitation, but declines in heart- and vision-related limitations have
      been important. CONCLUSION: Trends should continue to be monitored closely for
      both groups, since younger people have not experienced the improvements of the
      older group, but are its future members.

PMID- 24456684
TI  - A critical assessment of supported decision-making for persons aging with
      intellectual disabilities.
AB  - Supported decision-making is increasingly being promoted as an alternative to
      guardianship for persons aging with intellectual disabilities. Proponents argue
      that supported decision-making, unlike guardianship, empowers persons with
      disabilities by providing them with help in making their own decisions, rather
      than simply providing someone else to make decisions for them. To evaluate the
      empirical support for these claims, we reviewed the evidence base on supported
      decision-making. Our review found little such empirical research, suggesting that
      significant further research is warranted to determine whether--and under what
      conditions--supported decision-making can benefit persons with intellectual
      disabilities. Indeed, without more empirical evidence as to how supported
      decision-making functions in practice, it is too early to rule out the
      possibility it may actually disempower individuals with disabilities by
      facilitating undue influence by their alleged supporters. We therefore suggest
      several key areas for future research.

PMID- 24456685
TI  - Key goals and indicators for successful aging of adults with early-onset
      disability.
AB  - Substantial improvements have occurred in the longevity of several groups of
      individuals with early-onset disabilities, with many now surviving to advanced
      ages. This paper estimates the population of adults aging with early-onset
      disabilities at 12-15 million persons. Key goals for the successful aging of
      adults with early-onset disabilities are discussed, emphasizing reduction in
      risks for aging-related chronic disease and secondary conditions, while promoting
      social participation and independence. However, indicators suggest that elevated
      risk factors for aging-related chronic diseases, including smoking, obesity, and
      inactivity, as well as barriers to prevention and the diminished social and
      economic situation of adults with disabilities are continuing impediments to
      successful aging that must be addressed. Increased provider awareness that people
      with early-onset disabilities are aging and can age successfully and the
      integration of disability and aging services systems are transformative steps
      that will help adults with early-onset disability to age more successfully. 

PMID- 24456686
TI  - Bridging network divides: building capacity to support aging with disability
      populations through research.
AB  - Federal and state efforts to rebalance long-term services and supports (LTSS) in
      favor of home and community based over institutional settings has helped create
      structural bridges between the historically separated aging and disability LTSS
      networks by integrating and/or linking aging and disability systems. These
      changes present new opportunities to study bridging mechanisms and program
      related outcomes at national and local levels through federally sponsored LTSS
      initiatives termed Rebalancing programs. Rebalancing programs also offer
      opportunities to explore and understand the capacity of LTSS networks (age
      integrated or linked aging and disability systems) to serve aging with disability
      populations, persons who live with long-term chronic conditions or impairments
      such as multiple sclerosis, spinal cord injury, intellectual or developmental
      disabilities. To date, there is limited evidence based LTSS program and practice
      knowledge about this heterogeneous population such as met and unmet needs or
      interventions to support healthy aging. Efforts that center on bridging the
      larger fields of aging and disability in order to build new knowledge and engage
      in knowledge translation and translational research are critical for building
      capacity to support persons aging with disability in LTSS. Generating the
      investment in bridging aging and disability research across stakeholder group,
      including researchers and funders, is vital for these efforts. 

PMID- 24456687
TI  - Research gaps in the demography of aging with disability.
AB  - The evidence base regarding the demography of aging with disabilities in the US
      is growing yet substantial gaps remain. This paper summarizes seven major
      research gaps identified during a conference held in May 2012: how many adults
      are aging with disabilities; has survival improved for individuals aging with
      disabilities; can the notion of active life expectancy help inform understanding
      of aging with disability; what is the pattern of onset of secondary conditions
      for individuals aging with disabilities and how might such conditions be
      prevented and/or their debilitating effects ameliorated; what role has obesity
      had in shaping the population of individuals aging with disability; how do
      individuals aging with disability differ from those who develop disability later
      in life; and what are the long-term consequences of developing disability before
      late life for subsequent health, functioning, and socioeconomic outcomes.
      Bridging these gaps is crucial for enhancing understanding of this understudied
      population. 

PMID- 24456688
TI  - Policy concerns raised by the growing U.S. population aging with disability.
AB  - The number of Americans aging with disabilities will grow substantially in coming
      decades. Promulgating policies and practices to improve their independent
      functioning within communities and participation in daily life are therefore
      imperative, but the most effective approaches for meeting various needs are
      generally unknown. Historically, research addressing approaches targeting elderly
      individuals have differed in important ways (e.g., underlying models of
      disability) from studies involving younger persons aging with disabilities.
      Participants in a conference addressing this discordance identified six major
      areas requiring study: (1) resources to support independent living; (2) improving
      quality of life and participation in daily activities; (3) performing activities
      of daily living (ADL) and instrumental ADLs; (4) role of families; (5) medical
      care; and (6) concerns transcending sectors. As these investigations move
      forward, bridging the divide between approaches addressing elderly individuals
      versus persons with disabilities will be critical.

PMID- 24456690
TI  - Stem cell therapy: from evidence-based medicine to emotion-based medicine? The
      long Italian way for a scientific regulation.
AB  - On 23 May 2013, the Italian health minister decided to endorse a law regarding
      controversial stem cell-based therapies in 32 young terminally ill patients,
      shocking many scientists. According to the international scientific community,
      these therapies could be dangerous because they were not rigorously tested in
      humans. This decision was made after many days of media and judiciary pressure.
      Several lawsuits regarding stem cell-based therapies were brought before the
      judiciary districts of different Italian regions. We analyzed the Italian legal
      context regarding the field of pharmaceutical and medical devices, including the
      European Union trend. A national database - commonly used to manage legal
      materials for professional or educational purposes or both - was used to find
      relevant legal cases involving stem cell-based therapies. Stem cell-based
      therapies endorsed by the new Italian law have been the subject of an important
      discussion not only in the scientific community but also in various courts. We
      found several legal actions filed by parents in order to make stem cells
      available to their young children, who had serious neurodegenerative diseases.
      The majority of the analyzed legal disputes were settled in favor of the
      applicants, whereas only two decisions (Courts of Justice of Rome and Florence)
      rejected the complaint because of the absence of sufficient scientific data
      regarding stem cell-based therapies. The present Italian situation is influencing
      the destiny of future young patients and strongly impacting public and
      institutional opinion. It is a practical example of the complexity of the
      decision of not providing unapproved scientific stem cell-based therapies when
      medicine does not have any other alternative therapies.

PMID- 24456689
TI  - Dimer-dimer interaction of the bacterial selenocysteine synthase SelA promotes
      functional active-site formation and catalytic specificity.
AB  - The 21st amino acid, selenocysteine (Sec), is incorporated translationally into
      proteins and is synthesized on its specific tRNA (tRNA(Sec)). In Bacteria, the
      selenocysteine synthase SelA converts Ser-tRNA(Sec), formed by seryl-tRNA
      synthetase, to Sec-tRNA(Sec). SelA, a member of the fold-type-I pyridoxal 5'
      phosphate-dependent enzyme superfamily, has an exceptional homodecameric
      quaternary structure with a molecular mass of about 500kDa. Our previously
      determined crystal structures of Aquifex aeolicus SelA complexed with tRNA(Sec)
      revealed that the ring-shaped decamer is composed of pentamerized SelA dimers,
      with two SelA dimers arranged to collaboratively interact with one Ser-tRNA(Sec).
      The SelA catalytic site is close to the dimer-dimer interface, but the
      significance of the dimer pentamerization in the catalytic site formation
      remained elusive. In the present study, we examined the quaternary interactions
      and demonstrated their importance for SelA activity by systematic mutagenesis.
      Furthermore, we determined the crystal structures of "depentamerized" SelA
      variants with mutations at the dimer-dimer interface that prevent
      pentamerization. These dimeric SelA variants formed a distorted and inactivated
      catalytic site and confirmed that the pentamer interactions are essential for
      productive catalytic site formation. Intriguingly, the conformation of the non
      functional active site of dimeric SelA shares structural features with other fold
      type-I pyridoxal 5'-phosphate-dependent enzymes with native dimer or tetramer
      (dimer-of-dimers) quaternary structures. 

PMID- 24456691
TI  - An exploration of emergency department presentations related to high heel
      footwear in Victoria, Australia, 2006-2010.
AB  - BACKGROUND: Many women are warned against the dangers of wearing high heel
      footwear however there is limited empirical evidence demonstrating an association
      between wearing high heel with injury. Gait laboratory testing has found a higher
      heel height placed the foot in a position that increases the risk of ankle
      sprain. Women have also been surveyed about wearing high heels and approximately
      half of those reported inconvenience and pain after wearing a high heel shoe.
      This study aims to explore emergency department presentations of injuries and the
      estimated costs that have been directly attributed to wearing high heeled
      footwear within Victoria, Australia during 2006-2010. METHODS: The Victorian
      Emergency Minimum Dataset (VEMD) was searched for all injuries attributed to
      wearing high heel footwear presenting to emergency departments in Victoria
      Australia, between the years of 2006-2010. The VEMD produced a report detailing
      sex, age at presentation, month of presentation, time of day of presentation, day
      of presentation, location that injury occurred and type of injury for
      presentation. Monash Health in Victoria Australia, provided emergency department
      estimates for injury types to calculate an estimated cost of an acute injury
      related to wearing high heel footwear. RESULTS: There were 240 injuries
      presenting to Victorian emergency departments directly attributed to wearing high
      heeled footwear. The majority of people injured were women (n = 236) and all were
      less than 55 years of age. More injuries presented on a Sunday (n = 83) and more
      in the 8 am-12 pm time bracket (n = 64). There were also more injuries presenting
      in the months of November, December and January (n = 80). The most commonly
      injured body part was the ankle (n = 123). The emergency department estimate of
      the cost of these injuries over this time-frame was almost $72,000 (mean of
      $316.72 per presentation). CONCLUSIONS: People who wear high heel footwear on
      weekends appear to be at higher risk for injury that leads to emergency
      department presentation. However, there was not a large cost associated with
      emergency department presentations attributable to wearing high heel footwear
      over a 5 year period.

PMID- 24456692
TI  - The AML1/ETO target gene LAT2 interferes with differentiation of normal
      hematopoietic precursor cells.
AB  - The adaptor protein linker activator of T-cells 2 (LAT2) is a known AML1/ETO
      target gene whose function during normal hematopoiesis is unknown. We addressed
      the role of LAT2 during erythroid and myeloid differentiation of normal human
      CD34+ hematopoietic cells. LAT2 is expressed at low levels in CD34+ cells and
      upregulated during cytokine-induced myeloid and erythroid differentiation. Forced
      LAT2 expression leads to a delay of erythroid and myeloid differentiation keeping
      CD34+ cells in a more immature state, whereas LAT2 knockdown accelerates
      differentiation. It is tempting to speculate that by affecting the
      differentiation capacity of normal hematopoietic progenitors, LAT2 may contribute
      to the pathogenesis of AML. 

PMID- 24456693
TI  - BCR-ABL kinase domain mutations, including 2 novel mutations in imatinib
      resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical
      outcome.
AB  - Discovery of imatinib mesylate (IM) as the targeted BCR-ABL protein tyrosine
      kinase inhibitor (TKI) has resulted in its use as the frontline therapy for
      chronic myeloid leukemia (CML) across the world. Although high response rates are
      observed in CML patients who receive IM treatment, a significant number of
      patients develop resistance to IM. Resistance to IM in patients has been
      associated with a heterogeneous array of mechanisms of which point mutations
      within the ABL tyrosine kinase domain (TKD) are the frequently documented. The
      types and frequencies of mutations reported in different population studies have
      shown wide variability. We screened 125 Malaysian CML patients on IM therapy who
      showed either TKI refractory or resistance to IM to investigate the frequency and
      pattern of BCR-ABL kinase domain mutations among Malaysian CML patients
      undergoing IM therapy and to determine the clinical significance. Mutational
      screening using denaturing high performance liquid chromatography (dHPLC)
      followed by DNA sequencing was performed on 125 IM resistant Malaysian CML
      patients. Mutations were detected in 28 patients (22.4%). Fifteen different types
      of mutations (T315I, E255K, G250E, M351T, F359C, G251E, Y253H, V289F, E355G,
      N368S, L387M, H369R, A397P, E355A, D276G), including 2 novel mutations were
      identified, with T315I as the predominant type of mutation. The data generated
      from clinical and molecular parameters studied were correlated with the survival
      of CML patients. Patients with Y253H, M351T and E355G TKD mutations showed poorer
      prognosis compared to those without mutation. Interestingly, when the prognostic
      impact of the observed mutations was compared inter-individually, E355G and Y253H
      mutations were associated with more adverse prognosis and shorter survival
      (P=0.025 and 0.005 respectively) than T315I mutation. Results suggest that apart
      from those mutations occurring in the three crucial regions (catalytic domain, P
      loop and activation-loop), other rare mutations also may have high impact in the
      development of resistance and adverse prognosis. Presence of mutations in
      different regions of BCR-ABL TKD leads to different levels of resistance and
      early detection of emerging mutant clones may help in decision making for
      alternative treatment. Serial monitoring of BCR-ABL1 transcripts in CML patients
      allows appropriate selection of CML patients for BCR-ABL1 KD mutation analysis
      associated with acquired TKI resistance. Identification of these KD mutations is
      essential in order to direct alternative treatments in such CML patients. 

PMID- 24456694
TI  - Electromagnetic fields at extremely low frequencies and the risk for childhood
      leukemia: do we have enough information to warrant this association?

PMID- 24456695
TI  - The COPD assessment test (CAT) assists prediction of COPD exacerbations in high
      risk patients.
AB  - We evaluated the predictive value of the COPD assessment test (CATTM) for
      exacerbation in the following six months or time to first exacerbation among COPD
      patients with previous exacerbations. COPD outpatients with a history of
      exacerbation from 19 hospitals completed the CAT questionnaire and spirometry
      over six months. Exacerbation events were prospectively collected using a
      structured questionnaire. The baseline CAT score categorised into four groups (0
      9, 10-19, 20-29, and 30-40) showed strong prediction for time to first
      exacerbation and modest prediction for any exacerbation or moderate-severe
      exacerbation (AUC 0.83, 0.64, and 0.63 respectively). In multivariate analyses,
      the categorised CAT score independently predicted all three outcomes (p = 0.001
      or p < 0.001). Compared with the lowest CAT score category, the higher categories
      were associated with significantly shorter time to first exacerbation and higher
      exacerbation risks. The corresponding adjusted median time was >24, 14, 9, and 5
      weeks and the adjusted RR was 1.00, 1.30, 1.37, and 1.50 in the category of 0-9,
      10-19, 20-29, and 30-40 respectively. Exacerbation history (>=2 vs. 1 event in
      the past year) was related to time to first exacerbation (adjusted HR 1.35; p =
      0.023) and any exacerbation during the study period (adjusted RR 1.15; p =
      0.016). The results of this study support the use of the CAT as a simple tool to
      assist in the identification of patients at increased risk of exacerbations. This
      could facilitate timely and cost-effective implementation of preventive
      interventions, and improve health resource allocation. TRIAL REGISTRATION:
      Clinicaltrials.gov: NCT01254032.

PMID- 24456696
TI  - [Congenital hypogonadotropic hypogonadism and Kallmann syndrome in males].
AB  - Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are a
      group of rare disorders responsible for complete or partial pubertal failure due
      to lack or insufficient secretion of the pituitary gonadotropins LH and FSH. The
      underlying neuroendocrine abnormalities are classically divided into two main
      groups: molecular defects of the gonadotrope cascade leading to isolated
      normosmic CHH (nCHH), and developmental abnormalities affecting the hypothalamic
      location of GnRH neurons, but also olfactory bulbs and tracts morphogenesis and
      responsible for KS. Identification of genetic abnormalities related to CHH/KS has
      provided major insights into the pathways critical for the development,
      maturation and function of the gonadotrope axis. In patients affected by nCHH,
      particularly in familial cases, genetic alterations affecting GnRH secretion
      (mutations in GNRH1, GPR54/KISS1R and TAC3 and TACR3) or the GnRH sensitivity of
      gonadotropic cells (GNRHR) have been found. Mutations in KAL1, FGFR1/FGF8/FGF17,
      PROK2/PROKR2, NELF, CHD7, HS6ST1, WDR11, SEMA3A, SOX10, IL17RD2, DUSP6, SPRY4,
      and FLRT3 have been associated with KS but sometimes also with its milder
      hyposmic/normosmic CHH clinical variant. A number of observations, particularly
      in sporadic cases, suggest that CHH/KS is not always a monogenic mendelian
      disease as previously thought but rather a digenic or potentially oligogenic
      condition. Before the age of 18 years, the main differential diagnosis of
      isolated nCHH is the relatively frequent constitutional delay of growth and
      puberty (CDGP). However, in male patients with pubertal delay and low
      gonadotropin levels, the presence of micropenis and/or cryptorchidism argues
      strongly in favor of CHH and against CDGP. CHH/KS are not always congenital life
      long disorders as initially thought, because in nearly 10 % of patients the
      disease seems not permanent, as evidenced by partial recovery of the pulsatile
      activity of the hypothalamic-pituitary-gonadal axis after discontinuation of
      treatment in adulthood (the so-called reversible CHH/KS). The clinical and
      hormonal diagnosis and the therapeutic management as well as the genetic
      counseling of these patients will be discussed here based on the experience
      acquired in our department during the past 30 years, from monitoring more than
      400 patients with these rare conditions.

PMID- 24456697
TI  - Two cases of anakinra-induced neutropenia during auto-inflammatory diseases: drug
      reintroduction can be successful.

PMID- 24456698
TI  - Steps to Growing Up Healthy: a pediatric primary care based obesity prevention
      program for young children.
AB  - BACKGROUND: Leading medical organizations have called on primary care
      pediatricians to take a central role in the prevention of childhood obesity.
      Weight counseling typically has not been incorporated into routine pediatric
      practice due to time and training constraints. Brief interventions with simple
      behavior change messages are needed to reach high-risk children, particularly
      Latino and Black children who are disproportionately affected by obesity and
      related comorbidities. Steps to Growing Up Healthy (Added Value) is a randomized
      controlled trial testing the efficacy of brief motivational counseling (BMC)
      delivered by primary care clinicians and the added value of supplementing BMC
      with monthly contact by community health workers (CHW) in the prevention/reversal
      of obesity in Latino and Black children ages 2-4 years old. METHODS/DESIGN:
      Mother-child dyads (targeted n = 150) are recruited for this 12-month randomized
      trial at an inner-city pediatric primary care clinic and randomized to: 1) BMC
      delivered by clinicians and nurses at well, sick, and WIC visits with the goal of
      reducing obesogenic behaviors (BMC); 2) BMC plus monthly phone calls by a CHW
      (BMC + Phone); or 3) BMC plus monthly home visits by a CHW (BMC + Home). During
      BMC, the medical team facilitates the selection of a specific goal (i.e., reduce
      sugar sweetened beverage consumption) that is meaningful to the mother and
      teaches the mother simple behavioral strategies. Monthly contacts with CHWs are
      designed to identify and overcome barriers to goal progress. Dyads are assessed
      at baseline and 12 months and the primary outcome is change in the child's BMI
      percentile. We hypothesize that BMC + Phone and BMC + Home will produce greater
      reductions in BMI percentiles than BMC alone and that BMC + Home will produce
      greater reductions in BMI percentiles than BMC + Phone. DISCUSSION: Steps to
      Growing Up Healthy will provide important information about whether a brief
      primary care-based intervention that utilizes a motivational interviewing and
      goal setting approach can be incorporated into routine care and is sufficient to
      prevent/reverse obesity in young children. The study will also explore whether
      monthly contact with a community health worker bridges the gap between the clinic
      and the community and is an effective strategy for promoting obesity prevention
      in high-risk families. TRIAL REGISTRATION: ClinicalTrials.gov NCT01973153.

PMID- 24456699
TI  - Secular trends in serum lipid levels of a Middle Eastern adult population; 10
      years follow up in Tehran lipid and glucose study.
AB  - BACKGROUND: To examine trends in the population levels of serum lipids among a
      Middle-Eastern adult population with high prevalence of dyslipidemia. METHODS: A
      population-based cohort of adult Iranian participants, aged >=20 years underwent
      four consecutive examinations between 1999-2001 and 2008-2011. Trends in age and
      multivariate-adjusted mean lipid levels were calculated using generalized
      estimating equations. RESULTS: At each of the 4 assessments, there were
      significant decreases in levels of total cholesterol (TC) (multivariate-adjusted
      means, 5.21 vs. 4.88 mmol/L in men; 5.42 vs. 5.07 mmol/L in women), triglycerides
      (TGs) (2.11 vs. 1.94 mmol/L in men; 1.88 vs. 1.74 mmol/L in women), and an
      increase in HDL-C level in both genders (0.95 vs. 1.058 mmol/L in men; 1.103 vs.
      1.246 mmol/L in women) in multivariate analyses (all Ps <0.001); however, body
      mass index (BMI) significantly increased simultaneously (25.92 vs. 27.45 kg/m2 in
      men; 27.76 vs. 30.02 kg/m2 in women) (P < 0.001). There were significant (P <
      0.001) increases in fasting plasma glucose (FPG) levels only among men (5.35 vs.
      5.73 mmol/L). Results did not change after excluding participants that had
      cardiovascular disease or used lipid lowering drugs during follow-up. There were
      significant decreases in the prevalence of hypercholesterolemia, low HDL-C,
      hypertriglyceridemia (all Ps <0.001) during follow-up. Furthermore, the
      consumption of lipid lowering drugs significantly increased (P <0.001).
      CONCLUSION: During a 10 years follow-up, favorable trends were observed in the
      population levels of TC, triglycerides, HDL-C, which could not be fully accounted
      for by the increase observed in the consumption of lipid lowering drugs. These
      favorable trends were counterbalanced by the progressive increase in general
      obesity and FPG level.

PMID- 24456700
TI  - Impact of clomiphene citrate during ovarian stimulation on the luteal phase after
      GnRH agonist trigger.
AB  - The use of a gonadotrophin-releasing hormone (GnRH) agonist to trigger final
      oocyte maturation in a GnRH antagonist protocol has been associated with poorer
      clinical outcomes due to an increased luteal-phase defect. It has been shown that
      LH activity is crucial in a normal luteal phase. Studies assessing the LH
      concentrations after clomiphene citrate co-treatment have observed increased
      luteal-phase LH concentrations. The purpose of this prospective cohort study was
      to analyse the effect of clomiphene citrate on the endocrine profile in the
      luteal phase when using GnRH agonist trigger. This was evaluated in eight oocyte
      donors undergoing ovarian stimulation using clomiphene citrate in combination
      with recombinant FSH compared with a control group of five donors treated with
      recombinant FSH only. The endocrine profile was comparable in both groups, except
      for serum LH concentrations on the day after trigger (121.3+/-53.0IU/l versus
      52.9+/-21.5IU/l, respectively, P=0.022). No significant differences in LH
      concentrations were found on the day of trigger or 5days after oocyte retrieval.
      In conclusion, a luteal-phase defect was observed despite treatment with
      clomiphene citrate during ovarian stimulation. The use of gonadotrophin-releasing
      hormone (GnRH) agonist to trigger ovulation in IVF has been associated with
      poorer pregnancy outcomes due to an increased luteal-phase defect. The luteal
      phase is the last phase of the menstrual cycle and is defined as the period
      between ovulation and the beginning of pregnancy or menses. It has been shown the
      activity of LH is crucial in a normal luteal phase. Studies assessing the LH
      concentrations after clomiphene citrate, an oestrogen receptor inhibitor, co
      treatment have observed increased luteal-phase LH concentrations. The purpose of
      this prospective cohort study was to analyse the effect of clomiphene citrate on
      menstrual cycle day 2-6 on the hormone profile in the luteal phase when using
      GnRH agonist trigger. This was evaluated was in eight oocyte donors undergoing
      ovarian stimulation using recombinant FSH compared with a control cohort of
      donors treated with recombinant FSH only. The current prospective cohort study
      reports higher LH concentrations on the day after GnRH agonist trigger, but not
      5days after oocyte retrieval (i.e. in the luteal phase). In conclusion, a luteal
      phase defect was observed despite the administration of clomiphene citrate during
      ovarian stimulation. Additional treatment with clomiphene citrate in the
      follicular phase is therefore not a valid alternative to prevent luteal-phase
      defect after GnRH agonist trigger. 

PMID- 24456701
TI  - Semen quality and prediction of IUI success in male subfertility: a systematic
      review.
AB  - Many variables may influence success rates after intrauterine insemination (IUI),
      including sperm quality in the native and washed semen sample. A literature
      search was performed to investigate the threshold levels of sperm parameters
      above which IUI pregnancy outcome is significantly improved and/or the cut-off
      values reaching substantial discriminative performance in an IUI programme. A
      search of MEDLINE, EMBASE and Cochrane Library revealed a total of 983 papers.
      Only 55 studies (5.6%) fulfilled the inclusion criteria and these papers were
      analysed. Sperm parameters most frequently examined were: (i) inseminating motile
      count after washing: cut-off value between 0.8 and 5 million; (ii) sperm
      morphology using strict criteria: cut-off value ?5% normal morphology; (iii)
      total motile sperm count in the native sperm sample: cut-off value of 5-10
      million; and (iv) total motility in the native sperm sample: threshold value of
      30%. The results indicate a lack of prospective studies, a lack of
      standardization in semen testing methodology and a huge heterogeneity of patient
      groups and IUI treatment strategies. More prospective cohort trials and
      prospective randomized trials investigating the predictive value of semen
      parameters on IUI outcome are urgently needed. It is generally believed that
      intrauterine insemination (IUI) with homologous semen should be a first-choice
      treatment to more invasive and expensive techniques of assisted reproduction in
      cases of cervical, unexplained and moderate male factor subfertility. The
      rationale for the use of artificial insemination is to increase gamete density at
      the site of fertilization. Scientific validation of this strategy is difficult
      because literature is rather confusing and inconclusive. Many variables may
      influence success rates after IUI treatment procedures. It seems logical that
      sperm quality has to be one of the main determinants to predict IUI success.
      Clinical practice would benefit from the establishment of threshold levels for
      sperm parameters above which IUI pregnancy outcome is significantly improved and
      below which a successful outcome is unlikely. We performed a literature search to
      investigate if such threshold levels are known. Most striking were the lack of
      standardization in semen-testing methodology and the huge heterogeneity of
      patient groups and IUI treatment strategies. The four sperm parameters most
      frequently examined were: (i) inseminating motile count after washing: cut-off
      value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut
      off value >4% normal morphology; (iii) total motile sperm count in native sperm
      sample: cut-off value of 5-10 million; and (iv) total motility in native sperm
      sample: threshold value of 30%. This review identified an urgent need for more
      and better prospective cohort trials investigating the predictive value of semen
      parameters on IUI pregnancy rate. 

PMID- 24456702
TI  - First births with a simplified culture system for clinical IVF and embryo
      transfer.
AB  - This study reports the outcome results from a pilot clinical trial using a
      simplified laboratory method for human IVF. This system reproducibly generates de
      novo the atmospheric and culture conditions that support normal fertilization and
      preimplantation embryogenesis to the hatched blastocyst stage without the need
      for specialized medical-grade gases or equipment. Development from insemination
      to the hatched blastocyst stage occurs undisturbed in a completely closed system
      that enables timed performance assessments for embryo selection in situ that, in
      this study, involved single-embryo transfers on day 3. With the simplified
      culture system, 8/23 embryos implanted, one miscarried at 8weeks of gestation and
      seven healthy babies have been born. The methodology and results are discussed
      with regard to how this simplified system can be adopted worldwide to meet the
      growing need for accessible and affordable IVF. A common notion concerning the
      demographics of infertility is that it is largely a phenomenon associated with
      developed countries, where infertility treatments are commonplace. In fact, most
      infertile couples reside in developing/low-resource countries where infertility
      diagnosis and treatment is nonexistent, inaccessible or unaffordable by the vast
      majority of young men and women in need. The irony of this situation is that
      bilateral tubal occlusions, for which IVF was originally indicated and is the
      most effective treatment, is by far the most common cause of their infertility.
      We have addressed one aspect of this issue, the IVF laboratory, as part of a
      wider effort by the Walking Egg Project to design and establish small, dedicated
      centres in developing countries to provide assisted reproduction technologies
      that are affordable and accessible to a wider proportion of the population in
      need. The methods for conventional IVF designed to addresses tubal obstructions
      are relatively simple and free of complex instrumentation and the highly
      developed infrastructure common to high-resource centres. This simplified IVF
      system self-generates culture conditions in a closed system. After prolonged
      preclinical testing, a pilot clinical study was initiated in 2012 in Genk,
      Belgium. The findings suggest that a significant first step has been achieved in
      the effort to bring advanced assisted reproduction to developed countries using a
      low-resource but highly effective IVF system capable of bringing modern
      reproductive medicine to infertile couples in low-resource societies. 

PMID- 24456703
TI  - IVF with planned single-embryo transfer versus IUI with ovarian stimulation in
      couples with unexplained subfertility: an economic analysis.
AB  - Couples with unexplained subfertility are often treated with intrauterine
      insemination (IUI) with ovarian stimulation, which carries the risk of multiple
      pregnancies. An explorative randomized controlled trial was performed comparing
      one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles
      of IUI-ovarian stimulation in couples with unexplained subfertility and a poor
      prognosis for natural conception, to assess the economic burden of the treatment
      modalities. The main outcome measures were ongoing pregnancy rates and costs.
      This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian
      stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21%
      with IUI-ovarian stimulation, with two and three multiple pregnancies,
      respectively. The mean cost per included couple was significantly different:
      ?2781 with IVF-eSET and ?1876 with IUI-ovarian stimulation (P<0.01). The
      additional costs per ongoing pregnancy were ?2456 for IVF-eSET. In couples with
      unexplained subfertility, one cycle of IVF-eSET cost an additional ?900 per
      couple compared with three cycles of IUI-ovarian stimulation, for no increase in
      ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET
      results in higher ongoing pregnancy rates, IVF would be the preferred treatment.
      Couples that have been trying to conceive unsuccessfully are often treated with
      intrauterine insemination (IUI) and medication to improve egg production (ovarian
      stimulation). This treatment carries the risk of multiple pregnancies like twins.
      We performed an explorative study among those couples that had a poor prognosis
      for natural conception. One cycle of IVF with transfer of one selected embryo
      (elective single-embryo transfer, eSET) was compared with three cycles of IUI
      ovarian stimulation. The aim of this study was to assess the economic burden of
      both treatments. The Main outcome measures were number of good pregnancies above
      12weeks and costs. We randomly assigned 58 couples to IVF-eSET and 58 couples to
      IUI-ovarian stimulation. The ongoing pregnancy rates were comparable: 24% with
      IVF-eSET versus 21% with IUI-ovarian stimulation. There were two multiple
      pregnancies with IVF-eSET and three multiple pregnancies with IUI-ovarian
      stimulation. The mean cost per included couple was significantly different, ?2781
      with IVF-eSET and ?1876 with IUI-ovarian stimulation. The additional costs per
      ongoing pregnancy were ?2456 for IVF-eSET. In couples with unexplained
      subfertility, one cycle of IVF-eSET costed an additional ?900 per couple compared
      to three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy
      rates or decrease in multiple pregnancies. We conclude that IUI-ovarian
      stimulation is the preferred treatment to start with. When IVF-eSET results in a
      higher ongoing pregnancy rate (>38%), IVF would be the preferred treatment. 

PMID- 24456704
TI  - The effect of metronomic versus standard chemotherapy on the regulatory to
      effector T-cell equilibrium in cancer patients.
AB  - BACKGROUND: The host's immune system is crucially involved in cancer development
      and progression. The ratio of regulatory to effector T-cells, as well as the
      interplay of T-cells with therapeutic agents, impact on cancer prognosis. The
      current study aimed to comparatively investigate the effect of metronomic and
      standard chemotherapy on the number and functionality of peripheral regulatory
      and effector T-cells in cancer patients. METHODS: CD4+CD25+ regulatory and
      CD4+CD25- effector T-cells were purified from the peripheral blood of 36 cancer
      patients and co-cultured in the presence of a polyclonal stimulus. The
      proliferative capacity and frequency of CD4+CD25+/CD4+CD25- T-cells were analysed
      before and during various chemotherapeutic regimes, by ELISA and flow cytometry,
      respectively. RESULTS: Chemotherapy shifted immune responses in favour of
      regulatory T-cells. The relative ratio of regulatory to effector T-cells
      increased, and the T-cell-mediated suppressive activity of regulatory on effector
      T-cells was augmented. This effect was more profound in metronomic than in
      standard chemotherapeutic approaches. Moreover, an association between the
      chemotherapy strategy followed and the mode of action of specific drugs (anti
      mitotic, anti-DNA) was revealed. CONCLUSIONS: In comparison to standard
      chemotherapeutic strategies, metronomic approaches, though more patient-friendly,
      result in a significantly more prominent expansion of regulatory T-cells that
      aggravate the regulatory to effector T-cell imbalance. Our findings impact on the
      modulation of chemotherapy-treated patients' anti-tumor immunity and, thus, may
      be proven useful for selecting the most advantageous drug-delivery strategy,
      particularly when immunotherapeutics are eventually to be applied.

PMID- 24456705
TI  - In situ chemical exploration of underwater ecosystems with
      microsampling/enrichment device.
AB  - The study of organic compounds present in water surrounding marine organisms can
      be useful for a better understanding of ecosystem dynamics, since these compounds
      may be important in signaling. However, the detection of organic compounds
      underwater is challenging, as they are present at very low levels. We introduce
      in situ solid-phase microextraction (SPME) as a non-invasive and non-polluting
      technique for simultaneous underwater sampling and extraction of small molecules.
      Analyses were conducted with a LC-MS method using a benchtop orbitrap instrument
      in both positive and negative modes. We provided preliminary results on the
      ability of SPME fibers to extract simultaneously around 280 compounds with a wide
      range of polarities (logP from -2.6 to 15.3), including short-lived
      intermediates, directly from underwater. We envision that this approach can offer
      new opportunities to explore underwater ecosystems dynamics. 

PMID- 24456706
TI  - Evaluation of non-conventional polar modifiers on immobilized chiral stationary
      phases for improved resolution of enantiomers by supercritical fluid
      chromatography.
AB  - An evaluation of the use of non-conventional polar modifiers for the
      supercritical fluid chromatographic separation of enantiomers on immobilized
      chiral stationary phases is presented. The resolution of a group of nine
      commercially available racemates is studied on the Chiralpak IA, IB, IC, ID, IE,
      and IF chiral stationary phases using CO2-based eluents containing non
      conventional polar modifiers such as dichloromethane, chloroform,
      tetrahydrofuran, 2-methyl tetrahydrofuran, methyl tert-butyl ether, cyclopentyl
      methyl ether, acetone, ethyl acetate, toluene, 2,2,2-trifluoroethanol, and N,N
      dimethylformamide. Screening experiments and method development for the
      commercial racemates on the immobilized columns with the non-conventional
      solvents demonstrated an ability to adjust the retention and improve resolution.
      From these results we were able to assign a general eluotropic relationship
      between the non-conventional solvents and methanol. A general ability to
      selectively adjust chromatographic retention while improving analyte solubility
      can lead to improved preparative chromatographic performance. 

PMID- 24456707
TI  - Gas chromatography-mass spectrometry determination of earthy-musty odorous
      compounds in waters by two phase hollow-fiber liquid-phase microextraction using
      polyvinylidene fluoride fibers.
AB  - A rapid and sensitive method for the determination of earthy-musty odorous
      compounds, 2-methylisoborneol, 2-isopropyl-3-methoxy pyrazine, 2,4,6
      trichloroanisole, 2,3,6-trichloroanisole, and geosmin, in water samples has been
      developed. The method was based on coupling a new polyvinylidene fluoride (PVDF)
      hollow-fiber liquid-phase microextraction system with gas chromatography-mass
      spectrometry (GC-MS). The PVDF hollow fibers have high porosity and an enhanced
      solvent compatibility for extraction of the target analytes. Experimental
      conditions were optimized by investigating the type of extraction solvent, sample
      pH, sodium chloride concentration, stirring speed, extraction time, and GC-MS
      conditions. Under optimized conditions, the earthy-musty odorous compounds
      exhibited good linearity (R>0.995) in the concentration range of 6.2-250ng/L. The
      repeatability and reproducibility of the method were lower than 6.8% and 9.8%,
      respectively. The limit of detection and limit of quantification values were
      lower than 2.0 and 6.2ng/L, respectively. The analysis of different water samples
      such as tap, pond, rive and waste water indicated minimal matrix effects. Analyte
      recoveries for real samples spiked at different concentrations were between 84.4%
      and 117.5%. 

PMID- 24456708
TI  - Accurate measurements of frontal analysis for the determination of adsorption
      isotherms in supercritical fluid chromatography.
AB  - The implementation of the traditional FA method is difficult with classical
      supercritical fluid chromatography (SFC) instruments. The instrument mixer and
      other sources of extra-column volumes are large and significantly broaden the
      fronts of injected plugs, which diminishes the precision and accuracy of the FA
      method. An SFC instrument was modified to permit more accurate determinations of
      adsorption isotherm data. The sample, the modifier, and CO2 are separately pumped
      via small volume connection tubes into a small volume mixer (250MUL), where they
      are mixed into a homogeneous fluid fed to the column. The extra-column volumes
      and the column hold-up volume were accurately measured at each back pressure from
      the retention times of tracers. This modified instrument was used to measure the
      adsorption isotherm of S-naproxen by frontal analysis (FA) on a (R, R)-Whelk-O1
      column, using a mixture of methanol (20%, v/v) and CO2 as the mobile phase. Its
      performance is studied at several different back pressures from 100 to 210bar. In
      all the experiments, the total flow rate was kept to a low value (1mL/min) in
      order to minimize the variation of the equilibrium constant along the column.
      Although a suitable breakthrough curve could not be obtained at low back
      pressures (<150bar) due to the closeness to the critical point pressure of the
      methanol/CO2 mixture, excellent results were obtained at higher back pressures
      (>150bar), conditions remote from the critical point and breakthrough curves with
      very sharp front shocks are obtained. The RSDs of the profiles recorded at each
      back pressures are excellent, better than 1%. 

PMID- 24456710
TI  - Mitochondria and vesicles differ between adult and prepubertal sheep oocytes
      during IVM.
AB  - Oocytes from prepubertal animals have a reduced ability to undergo normal embryo
      development and produce viable offspring. The correct quantity, activity and
      cytoplasmic distribution of oocyte organelles are essential for oocyte
      maturation, fertilisation and subsequent embryo development. The aim of this
      study was to quantify the ultrastructural differences between oocytes from
      prepubertal lamb and adult ewes using electron microscopy and stereology. We also
      determined whether quantitative polymerase chain reaction (qPCR) methods give
      comparable estimates of mitochondrial number to stereology. Mean storage vesicle
      volume was greater in adult compared with lamb oocytes before IVM and decreased
      during maturation in both adult and lamb oocytes. Mitochondrial volume and number
      increased in adult oocytes during maturation; however, no increase was observed
      in lamb oocytes. Mitochondrial DNA copy number measured by qPCR showed no
      differences between adult and lamb oocytes. A different distribution of
      mitochondria was observed in lamb oocytes before maturation, while the percentage
      of hooded mitochondria increased during maturation in adult oocytes and decreased
      in the lamb. In conclusion, the present study has identified differences in the
      vesicles and mitochondria between adult and lamb oocytes from ewes that may
      contribute to reduced developmental competence in prepubertal oocytes. 

PMID- 24456709
TI  - A subset of chicken statoacoustic ganglion neurites are repelled by Slit1 and
      Slit2.
AB  - Mechanosensory hair cells in the chicken inner ear are innervated by bipolar
      afferent neurons of the statoacoustic ganglion (SAG). During development,
      individual SAG neurons project their peripheral process to only one of eight
      distinct sensory organs. These neuronal subtypes may respond differently to
      guidance cues as they explore the periphery in search of their target. Previous
      gene expression data suggested that Slit repellants might channel SAG neurites
      into the sensory primordia, based on the presence of robo transcripts in the
      neurons and the confinement of slit transcripts to the flanks of the prosensory
      domains. This led to the prediction that excess Slit proteins would impede the
      outgrowth of SAG neurites. As predicted, axonal projections to the primordium of
      the anterior crista were reduced 2-3 days after electroporation of either slit1
      or slit2 expression plasmids into the anterior pole of the otocyst on embryonic
      day 3 (E3). The posterior crista afferents, which normally grow through and
      adjacent to slit expression domains as they are navigating towards the posterior
      pole of the otocyst, did not show Slit responsiveness when similarly challenged
      by ectopic delivery of slit to their targets. The sensitivity to ectopic Slits
      shown by the anterior crista afferents was more the exception than the rule:
      responsiveness to Slits was not observed when the entire E4 SAG was challenged
      with Slits for 40 h in vitro. The corona of neurites emanating from SAG explants
      was unaffected by the presence of purified human Slit1 and Slit2 in the culture
      medium. Reduced axon outgrowth from E8 olfactory bulbs cultured under similar
      conditions for 24 h confirmed bioactivity of purified human Slits on chicken
      neurons. In summary, differential sensitivity to Slit repellents may influence
      the directional outgrowth of otic axons toward either the anterior or posterior
      otocyst. 

PMID- 24456711
TI  - Dynamic 3D shape of the plantar surface of the foot using coded structured light:
      a technical report.
AB  - BACKGROUND: The foot provides a crucial contribution to the balance and stability
      of the musculoskeletal system, and accurate foot measurements are important in
      applications such as designing custom insoles/footwear. With better understanding
      of the dynamic behavior of the foot, dynamic foot reconstruction techniques are
      surfacing as useful ways to properly measure the shape of the foot. This paper
      presents a novel design and implementation of a structured-light prototype system
      providing dense three dimensional (3D) measurements of the foot in motion. The
      input to the system is a video sequence of a foot during a single step; the
      output is a 3D reconstruction of the plantar surface of the foot for each frame
      of the input. METHODS: Engineering and clinical tests were carried out to test
      the accuracy and repeatability of the system. Accuracy experiments involved
      imaging a planar surface from different orientations and elevations and measuring
      the fitting errors of the data to a plane. Repeatability experiments were done
      using reconstructions from 27 different subjects, where for each one both right
      and left feet were reconstructed in static and dynamic conditions over two
      different days. RESULTS: The static accuracy of the system was found to be 0.3 mm
      with planar test objects. In tests with real feet, the system proved repeatable,
      with reconstruction differences between trials one week apart averaging 2.4 mm
      (static case) and 2.8 mm (dynamic case). CONCLUSION: The results obtained in the
      experiments show positive accuracy and repeatability results when compared to
      current literature. The design also shows to be superior to the systems available
      in the literature in several factors. Further studies need to be done to quantify
      the reliability of the system in clinical environments.

PMID- 24456712
TI  - Biological effects of cancer-secreted factors on human mesenchymal stem cells.
AB  - Mesenchymal stem cells or mesenchymal stromal cells (MSCs) have been considered
      as a carrier of therapeutic gene because of their inherent ability to migrate to
      the tumors, and yet there are controversial reports suggesting the tumor
      promoting and tumor-inhibiting effects of MSCs. Al-Toub and colleagues provide
      further insights into the cellular interactions between MSCs and tumors and
      demonstrate that conditioned media derived from different cancer cells could
      influence MSC phenotype and gene expression. These changes in MSCs may be
      modulated by the tumor-derived interleukin-1 beta (IL-1beta) and transforming
      growth factor-beta (TGF-beta) signaling.

PMID- 24456713
TI  - Dentin hypersensitivity induces anxiety and increases corticosterone serum levels
      in rats.
AB  - AIMS: Investigate the relationships between experimentally induced dentin
      hypersensitivity (DH) with behavioral, endocrine and dentin erosion data.
      METHODS: Male Wistar rats divided into four groups, two controls and two
      experimental, received tap water or isotonic solution (Gatorade(r), lemon, pH2.7)
      for 30 or 45 days. The DH test was performed by a cold water stimulus on molars.
      A score (0-3) was given to the rats' pain response. Anxiety was evaluated by the
      elevated plus maze model and by serum corticosterone levels. The dentin erosion
      was observed by scanning electron microscopy (SEM). Anatomopathological studies
      were performed on the stomach, adrenal, kidney, and liver. RESULTS: Relative to
      control groups, experimental rats showed: 1) increased hypersensitivity scores
      (control group, 0; experimental groups, 2 (limits 0.5-3) on the 30th day and 2
      (limits 1-3) on the 45th day); 2) reduced percentage of time and entries in the
      open arms and in serum corticosterone levels; 3) totally exposed dentinal tubules
      on the 30th day in SEM analysis of the teeth; and 4) no alterations in the
      anatomopathological and histological evaluations. CONCLUSIONS: The treatment with
      isotonic solution for 30 days was able to induce DH after erosive challenge and
      severe DH was observed after isotonic solution treatment for 45 days. The pain
      induced by cold stimuli was consistent with the grade of DH. The close
      relationships between dental erosion, response to pain, serum levels of
      corticosterone and the EPM behavior responses reveal the effects of DH at several
      levels.

PMID- 24456714
TI  - Clinical outcome of postoperative highly conformal versus 3D conformal
      radiotherapy in patients with malignant pleural mesothelioma.
AB  - BACKGROUND: Radiotherapy (RT) is currently under investigation as part of a
      trimodality treatment of malignant pleural mesothelioma (MPM). The introduction
      of highly conformal radiotherapy (HCRT) technique improved dose delivery and
      target coverage in comparison to 3-dimensional conformal radiotherapy (3DCRT).
      The following study was undertaken to investigate the clinical outcome of both
      radiation techniques. METHODS: Thirty-nine MPM patients were treated with
      neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant RT.
      Twenty-five patients were treated with 3DCRT, and 14 with HCRT (Intensity
      modulated radiotherapy or volumetric modulated arc therapy). Overall survival,
      disease free survival, locoregional recurrence and pattern of recurrence were
      assessed. A matched pair analysis was performed including 11 patients of each
      group. RESULTS: After matching for gender, age, histology, tumor stage and
      resection status, HCRT seemed superior to 3DCRT with a local relapse rate of
      27.3% compared to 72.7% after 3DCRT (p = 0.06). The median time to local relapse
      was increased by 49% with HCRT in comparison to 3DCRT from 10.9 +/- 5.4 months to
      16.2 +/- 3.1 months (p = 0.06). The median overall survival was 22.3 +/- 15.3
      months for HCRT and 21.2 +/- 9.2 months for 3DCRT (p = 0.57). Recurrence analysis
      showed that in-field local relapses occurred in previously underdosed regions of
      the tumor bed in 16% of patients treated with 3DCRT and in 0% of HCRT patients.
      CONCLUSIONS: The use of HCRT increases the probability of local control as
      compared to 3DCRT by improving target volume coverage. HCRT did not improve
      overall survival in this patient series due to the high rate of distant
      recurrences.

PMID- 24456715
TI  - Contemporary incidence, predictors, and outcomes of acute kidney injury in
      patients undergoing percutaneous coronary interventions: insights from the NCDR
      Cath-PCI registry.
AB  - OBJECTIVES: This study sought to examine the contemporary incidence, predictors
      and outcomes of acute kidney injury in patients undergoing percutaneous coronary
      interventions. BACKGROUND: Acute kidney injury (AKI) is a serious and potentially
      preventable complication of percutaneous coronary interventions (PCIs) that is
      associated with adverse outcomes. The contemporary incidence, predictors, and
      outcomes of AKI are not well defined, and clarifying these can help identify high
      risk patients for proactive prevention. METHODS: A total of 985,737 consecutive
      patients underwent PCIs at 1,253 sites participating in the National
      Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011.
      AKI was defined on the basis of changes in serum creatinine level in the hospital
      according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable
      regression analyses with generalized estimating equations, we identified patient
      characteristics associated with AKI. RESULTS: Overall, 69,658 (7.1%) patients
      experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable
      analyses, the factors most strongly associated with development of AKI included
      ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio [OR]:
      2.60; 95% confidence interval [CI]: 2.53 to 2.67), severe chronic kidney disease
      (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80
      to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34%
      for those requiring dialysis compared with 0.5% for patients without AKI (p <
      0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p <
      0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p < 0.001) remained
      independent predictors of in-hospital mortality. CONCLUSIONS: Approximately 7% of
      patients undergoing a PCI experience AKI, which is strongly associated with in
      hospital mortality. Defining strategies to minimize the risk of AKI in patients
      undergoing PCI are needed to improve the safety and outcomes of the procedure.

PMID- 24456716
TI  - The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of
      femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in
      human randomized trial of low-dose drug-coated balloon versus uncoated balloon
      angioplasty.
AB  - OBJECTIVES: This study sought to evaluate the safety and efficacy of the Lutonix
      drug-coated balloon (DCB) coated with 2 MUg/mm(2)paclitaxel and a
      polysorbate/sorbitol carrier for treatment of femoropopliteal lesions.
      BACKGROUND: Percutaneous treatment of peripheral vascular disease is associated
      with a high recurrence. Paclitaxel-coated balloons at 3 MUg/mm(2) formulated
      differently have shown promising results with reduced restenosis. Methods
      Subjects at 9 centers with Rutherford class 2 to 5 femoropopliteal lesions were
      randomized between June 2009 and December 2009 to treatment with Lutonix DCB (n =
      49) versus uncoated balloons (control group [n = 52]), stratified by whether
      balloon-only treatment (n = 75) or stenting (n = 26) was intended. The primary
      endpoint was angiographic late lumen loss at 6 months. Secondary outcomes
      included adjudicated major adverse events (death, amputation, target lesion
      thrombosis, reintervention), functional outcomes, and pharmacokinetics. RESULTS:
      Demographic, peripheral vascular disease, and lesion characteristics were
      matched, with mean lesion length of 8.1 3.8 cm and 42% total occlusions. At 6
      months, late lumen loss was 58% lower for the Lutonix DCB group (0.46 1.13 mm)
      than for the control group (1.09 1.07 mm; p = 0.016). Composite 24-month major
      adverse events were 39% for the DCB group, including 15 target lesion
      revascularizations, 1 amputation, and 4 deaths versus 46% for uncoated balloon
      group, with 20 target lesion revascularizations, 1 thrombosis, and 5 deaths.
      Pharmacokinetics showed biexponential decay with peak concentration (Cmax) of 59
      ng/ml and total observed exposure (AUC(all)) of 73 ng h/ml. For successful DCB
      deployment excluding 8 malfunctions, 6-month late lumen loss was 0.39 mm and the
      24-month target lesion revascularization rate was 24%. CONCLUSIONS: Treatment of
      femoropopliteal lesions with the low-dose Lutonix DCB reduced late lumen loss
      with safety comparable to that of control angioplasty. (LEVANT I, The Lutonix
      Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis;
      NCT00930813)

PMID- 24456717
TI  - Initial success rate of percutaneous coronary intervention for chronic total
      occlusion in a native coronary artery is decreased in patients who underwent
      previous coronary artery bypass graft surgery.
AB  - OBJECTIVES: This study sought to compare the initial success rate of percutaneous
      coronary intervention (PCI) for chronic total occlusion (CTO) in a native
      coronary artery (NCA) in patients with and without previous coronary artery
      bypass grafting (CABG) and to assess predictive factors. BACKGROUND: Landmark
      novel wiring techniques for CTO-PCI have contributed to improvement in the
      initial success of CTO-PCI. However, challenges persist in CTO-PCI in NCA in
      pCABG patients. METHODS: Patients who underwent CTO-PCI in an NCA were selected
      and classified into 2 groups: pCABG (206 PCIs in 153 patients) and nCABG (1,431
      PCIs in 1,139 patients). RESULTS: CTO was located more often in the left anterior
      descending artery (p = 0.0003), and severe calcified lesions were observed more
      frequently in the pCABG group (p < 0.0001). Although the retrograde attempt was
      tried more frequently in the pCABG group, the CTO-PCI success rate was
      significantly lower in the pCABG patients than in the nCABG patients (71% vs.
      83%). Longer procedural time and greater radiation exposure were needed in the
      pCABG patients. Logistic regression analysis among the pCABG patients revealed
      that intravascular ultrasound use and parallel wiring were positive factors, and
      lesion tortuosity was a negative factor. CONCLUSIONS: The initial success rate of
      CTO-PCI of an NCA in the pCABG group was significantly decreased compared with
      that in the nCABG group. Anatomic complexity and unstable hemodynamic state were
      unfavorable conditions. This study reveals that the issues to be overcome are
      lying with CTO revascularization in an NCA in pCABG patients.

PMID- 24456718
TI  - Short- and long-term implications of a bioresorbable vascular scaffold
      implantation on the local endothelial shear stress patterns.

PMID- 24456719
TI  - Three-dimensional optical coherence tomography for guidance of complex
      percutaneous coronary interventions.

PMID- 24456720
TI  - Massive coronary aneurysm after multiple percutaneous interventions: an
      iatrogenic or unpreventable disaster?

PMID- 24456721
TI  - Persistent high residual shunt rate 2 years after patent foramen ovale closure
      using a bioabsorbable device.

PMID- 24456722
TI  - P2Y12-based platelet function assays should be complemented with cyclooxygenase
      dependent testing in framing the therapeutic windows for dual antiplatelet
      therapy.

PMID- 24456723
TI  - Looking for the native annulus after transcatheter aortic valve replacement?

PMID- 24456724
TI  - Reply: P2Y12-Based platelet function assays should be complemented with
      cyclooxygenase-dependent testing in framing the therapeutic windows for dual
      antiplatelet therapy.

PMID- 24456725
TI  - Reply: Looking for the native annulus after transcatheter aortic valve
      replacement?

PMID- 24456726
TI  - Is time of renal hypoperfusion an important variable in determining response to
      renal artery revascularization?

PMID- 24456727
TI  - The "chicken little" of renal stent trials: the CORAL trial in perspective.

PMID- 24456728
TI  - Anomalous right coronary artery from the proximal left anterior descending
      artery: a rare finding and its clinical significance.

PMID- 24456729
TI  - Primary percutaneous intervention in a patient with anterior and inferior wall
      myocardial infarction because of a rare coronary artery anomaly.

PMID- 24456730
TI  - Assessing the construct validity and reliability of the Parental Perception on
      Antibiotics (PAPA) scales.
AB  - BACKGROUND: The overuse of antibiotics is becoming an increasing concern.
      Antibiotic resistance, which increases both the burden of disease, and the cost
      of health services, is perhaps the most profound impact of antibiotics overuse.
      Attempts have been made to develop instruments to measure the psychosocial
      constructs underlying antibiotics use, however, none of these instruments have
      undergone thorough psychometric validation. This study evaluates the psychometric
      properties of the Parental Perceptions on Antibiotics (PAPA) scales. The PAPA
      scales attempt to measure the factors influencing parental use of antibiotics in
      children. METHODS: 1111 parents of children younger than 12 years old were
      recruited from primary schools' parental meetings in the Eastern Province of
      Saudi Arabia from September 2012 to January 2013. The structure of the PAPA
      instrument was validated using Confirmatory Factor Analysis (CFA) with
      measurement model fit evaluated using the raw and scaled chi2, Goodness of Fit
      Index, and Root Mean Square Error of Approximation. RESULTS: A five-factor model
      was confirmed with the model showing good fit. Constructs in the model include:
      Knowledge and Beliefs, Behaviors, Sources of information, Adherence, and
      Awareness about antibiotics resistance. The instrument was shown to have good
      internal consistency, and good discriminant and convergent validity. CONCLUSION:
      The availability of an instrument able to measure the psychosocial factors
      underlying antibiotics usage allows the risk factors underlying antibiotic use
      and overuse to now be investigated.

PMID- 24456731
TI  - Carcinoid heart disease.

PMID- 24456732
TI  - Large changes in PaO2 oscillation amplitude with respiratory rate are not
      measurement artifact.

PMID- 24456733
TI  - Dietary resveratrol supplementation normalizes gene expression in the hippocampus
      of streptozotocin-induced diabetic C57Bl/6 mice.
AB  - Diabetes is associated with cognitive impairment and brain aging, with
      alterations in hippocampal neurogenesis and synaptic plasticity implicated in
      these changes. As the prevalence of diabetes continues to rise, readily
      implemented strategies are increasingly needed in order to protect the brain's
      cognitive functions. One possibility is resveratrol (RES) (3,5,4-
      trihydroxystilbene), a polyphenol of the phytoalexin family that has been shown
      to be protective in a number of neuropathology paradigms. In the present study,
      we sought to determine whether dietary supplementation with RES has potential for
      the protection of cognitive functions in diabetes. Diabetes was induced using
      streptozotocin, and once stable, animals received AIN93G rodent diet supplemented
      with RES for 6 weeks. Genome-wide expression analysis was conducted on the
      hippocampus and genes of interest were confirmed by quantitative, real-time
      polymerase chain reaction. Genome-wide gene expression analysis of the
      hippocampus revealed that RES supplementation of the diabetic group resulted in
      481 differentially expressed genes compared to non-supplemented diabetic mice.
      Intriguingly, gene expression that was previously found significantly altered in
      the hippocampus of diabetic mice, and that is implicated in neurogenesis and
      synaptic plasticity (Hdac4, Hat1, Wnt7a, ApoE), was normalized following RES
      supplementation. In addition, pathway analysis revealed Jak-Stat signaling was
      the most significantly enriched pathway. The Jak-Stat pathway induces a pro
      inflammatory signaling cascade, and we found most genes involved in this cascade
      (e.g. Il15, Il22, Socs2, Socs5) had significantly lower expression following RES
      supplementation. These data indicate RES could be neuroprotective and beneficial
      for the maintenance of cognitive function in diabetes.

PMID- 24456734
TI  - Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter
      and elevating genomic methylation in mice fed a high-fat diet.
AB  - Aberrant DNA methylation contributes to the abnormality of hepatic gene
      expression, one of the main factors in the pathogenesis of nonalcoholic fatty
      liver disease (NAFLD). Betaine is a methyl donor and has been considered to be a
      lipotropic agent. However, whether betaine supplementation improves NAFLD via its
      effect on the DNA methylation of specific genes and the genome has not been
      explored. Male C57BL/6 mice were fed either a control diet or high-fat diet (HFD)
      supplemented with 0%, 1% and 2% betaine in water (wt/vol) for 12 weeks. Betaine
      supplementation ameliorated HFD-induced hepatic steatosis in a dose-dependent
      manner. HFD up-regulated FAS and ACOX messenger RNA (mRNA) expression and down
      regulated PPARalpha, ApoB and MTTP mRNA expression; however, these alterations
      were reversed by betaine supplementation, except ApoB. MTTP mRNA expression was
      negatively correlated with the DNA methylation of its CpG sites at -184, -156, 
      63 and -60. Methylation of these CpG sites was lower in both the 1% and 2%
      betaine-supplemented groups than in the HFD group (averages; 25.55% and 14.33%
      vs. 30.13%). In addition, both 1% and 2% betaine supplementation significantly
      restored the methylation capacity [S-adenosylmethionine (SAM) concentration and
      SAM/S-adenosylhomocysteine ratios] and genomic methylation level, which had been
      decreased by HFD (0.37% and 0.47% vs. 0.25%). These results suggest that the
      regulation of aberrant DNA methylation by betaine might be a possible mechanism
      of the improvements in NAFLD upon betaine supplementation. 

PMID- 24456735
TI  - Betaine supplementation protects against high-fructose-induced renal injury in
      rats.
AB  - High fructose intake causes metabolic syndrome, being an increased risk of
      chronic kidney disease development in humans and animals. In this study, we
      examined the influence of betaine on high-fructose-induced renal damage involving
      renal inflammation, insulin resistance and lipid accumulation in rats and
      explored its possible mechanisms. Betaine was found to improve high-fructose
      induced metabolic syndrome including hyperuricemia, dyslipidemia and insulin
      resistance in rats with systemic inflammation. Betaine also showed a protection
      against renal dysfunction and tubular injury with its restoration of the
      increased glucose transporter 9 and renal-specific transporter in renal brush
      bolder membrane and the decreased organic anion transporter 1 and adenosine
      triphosphate-binding cassette transporter 2 in the renal cortex in this model.
      These protective effects were relevant to the anti-inflammatory action by
      inhibiting the production of inflammatory cytokines including interleukin (IL)
      1beta, IL-18, IL-6 and tumor necrosis factor-alpha in renal tissue of high
      fructose-fed rat, being more likely to suppress renal NOD-like receptor
      superfamily, pyrin domain containing 3 inflammasome activation than nuclear
      factor kappaB activation. Subsequently, betaine with anti-inflammation
      ameliorated insulin signaling impairment by reducing the up-regulation of
      suppressor of cytokine signaling 3 and lipid accumulation partly by regulating
      peroxisome proliferator-activated receptor alpha/palmityltransferase
      1/carnitine/organic cation transporter 2 pathway in kidney of high-fructose-fed
      rats. These results indicate that the inflammatory inhibition plays a pivotal
      role in betaine's improvement of high-fructose-induced renal injury with insulin
      resistance and lipid accumulation in rats. 

PMID- 24456736
TI  - Relationship of cytokines, oxidative stress and GI motility with bacterial
      overgrowth in ulcerative colitis patients.
AB  - BACKGROUND: Ulcerative colitis (UC) is idiopathic, chronic and relapsing
      inflammatory bowel disease. Factors which initiate and perpetuate UC are not well
      understood. It is still unclear if any relationship exists between cytokines,
      oxidative stress, gastrointestinal (GI) motility, and small intestinal bacterial
      overgrowth (SIBO) in UC patients. GOALS: To examine the relationship between
      these factors among UC patients. METHODS: A total of 120 UC patients and 125 age
      and sex matched controls with no GI symptoms were enrolled. Plasma levels of IL
      6, IL-8, TNF-alpha and IL-10 were measured in all subjects by using ELISA. Lipid
      peroxidation (LPO) and reduced glutathione (GSH) were measured by standard
      methods. Orocecal transit time (OCTT) and SIBO were measured by lactulose and
      glucose hydrogen breath tests respectively. RESULTS: Out of the 120 UC patients,
      74 were male with mean+/-SD age of 45.6+/-17.5years. Plasma levels of IL-6, IL-8,
      TNF-alpha and IL-10 in UC patients were significantly higher (p<0.01) as compared
      to controls. LPO in UC patients was significantly increased (p<0.01) while GSH
      was significantly decreased (p<0.01) as compared to controls. OCTT and SIBO were
      significantly higher in UC patients as compared to controls. UC patients with
      elevated inflammatory cytokines showed delayed OCTT and increased SIBO. It was
      also observed that there was a significant correlation between SIBO with IL-6, IL
      8, TNF-alpha, and IL-10, LPO and GSH. CONCLUSION: This study indicates that
      increase in cytokines and decrease in anti-oxidants in UC patients would have
      resulted in oxidative stress causing delayed GI motility leading to SIBO.

PMID- 24456737
TI  - High prevalence of abdominal aortic aneurysm in patients with three-vessel
      coronary artery disease.
AB  - OBJECTIVES: Currently, the prevalence of abdominal aortic aneurysm (AAA) in
      patients with coronary artery disease (CAD) and the correlation between CAD
      severity and AAA prevalence are not clearly known. We conducted a prospective
      study to determine the prevalence of AAA in patients undergoing coronary
      angiography and to determine the risk factors and a coronary profile associated
      with AAA. METHODS: Over an 18-month period, abdominal aortic ultrasound was
      performed on 1,000 patients undergoing coronary angiography for suspected or
      known CAD, or prior to valve surgery. Clinical characteristics and coronary
      profile were collected from the patients. RESULTS: The overall number of
      previously repaired, already diagnosed, and new cases of AAA in the study
      population was 42, yielding a prevalence of 4.2%. Among the patients with newly
      detected AAAs, only two had an AAA diameter of >54 mm and were therefore treated
      surgically. In men aged >= 65 years, the prevalence reached 8.6%, while in men
      with three-vessel CAD it was 14.4%. Multivariate analysis showed that age >= 65
      years (p = .003), male gender (p = .003), family history of AAA (p = .01),
      current smoking (p = .002), and three-vessel CAD (p < .001) were significantly
      associated with a higher prevalence of AAA. CONCLUSION: The prevalence of AAA was
      high in men aged >= 65 years and in those with three-vessel CAD regardless of
      age. While our findings do not prove the cost-effectiveness of screening for AAA
      in these high risk patients, they do support the usefulness of a quick ultrasound
      examination of the abdominal aorta during routine transthoracic echocardiography
      in such patients.

PMID- 24456738
TI  - The new C3 Gore Excluder stent-graft: single-center experience with 100 patients.
AB  - OBJECTIVES: To present results from the first 100 patients treated with the new
      C3 Gore Excluder stent-graft in a single institution. METHODS: All patients
      treated with the C3 Excluder stent-graft between August 2010 and July 2013 in our
      institution were included. Patient demographics, treatment indication, need for
      intraoperative stent-graft repositioning, immediate technical success, survival,
      endoleak and migration rate, and need for reintervention during follow-up were
      analyzed. RESULTS: A total of 100 patients (86% male, mean age 71.1 +/- 9.3
      years) were enrolled. Elective abdominal aortic aneurysm (AAA) was the most
      common indication for treatment (n = 90), followed by common iliac artery
      aneurysm (n = 5), ruptured AAA (n = 2), type Ia endoleak (n = 1), and type IV
      endoleak (n = 1) after prior EVAR, and penetrating aortic ulcer (n = 1).
      Technical success was achieved in 98 patients. In two patients a small type I
      endoleak persisted at completion angiography, but had disappeared at the first
      control computed tomography angiogram. Stent-graft repositioning after initial
      deployment was required in 49 patients, almost equally distributed for level and
      contralateral gate reorientation. Exact positioning of the proximal trunk was
      achieved in 98 patients, with the remaining two cases within 5 mm of the intended
      location. Adverse events related to repositioning maneuvers were noticed in two
      cases. Mean follow-up duration was 12.2 +/- 9.4 months (range 0-36 months). Eight
      patients died, none from aneurysm related causes. Cumulative patient survival was
      96.2 +/- 2.1% at 1 year, and 84 +/- 6.1% at 2 years, respectively. No migration,
      or type I or III endoleak was detected during follow-up. Estimated freedom from
      reintervention was 96 +/- 2.4% at 1 year, and 91 +/- 5.2% at 2 years,
      respectively. CONCLUSIONS: The new C3 Excluder stent-graft provides excellent
      short-term outcomes and offers important advantages in terms of stent-graft
      repositioning to achieve high proximal deployment accuracy. Longer follow-up is
      required to confirm improved long-term outcome compared with the previous
      generation Excluder stent-graft.

PMID- 24456739
TI  - A novel strategy to translate the biomechanical rupture risk of abdominal aortic
      aneurysms to their equivalent diameter risk: method and retrospective validation.
AB  - OBJECTIVE: To translate the individual abdominal aortic aneurysm (AAA) patient's
      biomechanical rupture risk profile to risk-equivalent diameters, and to
      retrospectively test their predictability in ruptured and non-ruptured aneurysms.
      METHODS: Biomechanical parameters of ruptured and non-ruptured AAAs were
      retrospectively evaluated in a multicenter study. General patient data and high
      resolution computer tomography angiography (CTA) images from 203 non-ruptured and
      40 ruptured aneurysmal infrarenal aortas. Three-dimensional AAA geometries were
      semi-automatically derived from CTA images. Finite element (FE) models were used
      to predict peak wall stress (PWS) and peak wall rupture index (PWRI) according to
      the individual anatomy, gender, blood pressure, intra-luminal thrombus (ILT)
      morphology, and relative aneurysm expansion. Average PWS diameter and PWRI
      diameter responses were evaluated, which allowed for the PWS equivalent and PWRI
      equivalent diameters for any individual aneurysm to be defined. RESULTS: PWS
      increased linearly and PWRI exponentially with respect to maximum AAA diameter. A
      size-adjusted analysis showed that PWS equivalent and PWRI equivalent diameters
      were increased by 7.5 mm (p = .013) and 14.0 mm (p < .001) in ruptured cases when
      compared to non-ruptured controls, respectively. In non-ruptured cases the PWRI
      equivalent diameters were increased by 13.2 mm (p < .001) in females when
      compared with males. CONCLUSIONS: Biomechanical parameters like PWS and PWRI
      allow for a highly individualized analysis by integrating factors that influence
      the risk of AAA rupture like geometry (degree of asymmetry, ILT morphology, etc.)
      and patient characteristics (gender, family history, blood pressure, etc.). PWRI
      and the reported annual risk of rupture increase similarly with the diameter.
      PWRI equivalent diameter expresses the PWRI through the diameter of the average
      AAA that has the same PWRI, i.e. is at the same biomechanical risk of rupture.
      Consequently, PWRI equivalent diameter facilitates a straightforward
      interpretation of biomechanical analysis and connects to diameter-based
      guidelines for AAA repair indication. PWRI equivalent diameter reflects an
      additional diagnostic parameter that may provide more accurate clinical data for
      AAA repair indication.

PMID- 24456740
TI  - Apolipoprotein E polymorphism is associated with lower extremity deep venous
      thrombosis: color-flow Doppler ultrasound evaluation.
AB  - INTRODUCTION: Apolipoprotein E (apoE) is a member of apolipoprotein family, and
      its gene polymorphisms seem to have some impact among patients with
      cardiovascular disease. However, its role in the lower extremity deep venous
      thrombosis (LEDVT) has not been well studied. The objective of this study was to
      investigate the potential association between APOE gene polymorphisms and LEDVT.
      MATERIALS AND METHODS: A hospital-based case-control study was conducted in 300
      patients with LEDVT by color-flow Doppler ultrasound and 300 age- and gender
      matched healthy controls. Polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) assay was applied to assess the APOE gene polymorphisms.
      RESULTS: Patients with LEDVT had a significantly higher frequency of APOE E3/E4
      genotype [odds ratio (OR) =1.48, 95% confidence interval (CI) = 1.05, 2.10; P =
      0.03] than healthy controls. When stratifying by family history of LEDVT, it was
      found that patients with positive family history of LEDVT had a significantly
      higher frequency of APOE E3/E4 genotype (OR =1.68, 95% CI = 1.04, 0.95; P =
      2.70). When stratifying by smoking status, presence of varicose veins, type 2
      diabetes mellitus and any hormone administration before, no significant
      differences were found in any groups. CONCLUSION: Our study suggested that APOE
      E3/E4 genotype was associated with a higher LEDVT risk. Additional studies are
      needed to confirm this finding.

PMID- 24456741
TI  - Convergence and divergence in reports of maternal support following childhood
      sexual abuse: prevalence and associations with youth psychosocial adjustment.
AB  - This study examined the convergence and divergence in mothers' and children's
      reports of maternal support following disclosures of childhood sexual abuse
      (CSA). One hundred and twenty mothers and their children (ages 7-17 years)
      reported on two aspects of support following CSA disclosures: mothers' belief in
      the child's disclosure and parent-child discussion of the abuse incident. Whereas
      62% of mothers' and children's reports on mothers' belief of the disclosure
      positively converged (i.e., both reported that mothers "completely believed" the
      child's disclosure), 37% of mothers' and children's reports diverged, and the
      remaining 1% negatively converged (i.e., both reported that the mother only
      believed the child "somewhat"). Positively convergent responses were associated
      with youths' lower risk for tobacco and illicit drug use. Forty-four percent of
      mothers' and children's reports on whether details of the CSA were discussed
      positively converged (i.e., both reported that details were discussed), 33%
      diverged, and 23% negatively converged (i.e., both reported that details were not
      discussed). Relative to other patterns of reporting, negatively convergent
      responses were associated with higher levels of trauma symptoms. Findings have
      implications for identifying high-risk mother-child dyads based on patterns of
      informant reporting following CSA. 

PMID- 24456742
TI  - Early life emotional neglect and HIV risk taking among men using the Internet to
      find other men for unprotected sex.
AB  - PURPOSE: Using a Syndemics Theory conceptual model, this study examines the
      relationship between emotional neglect experiences during childhood and/or
      adolescence and involvement in HIV risk taking in a sample of adult men who
      actively seek partners for unprotected sex via the Internet. METHODS: The study
      was based on a national random sample of 332 MSM who use the Internet to seek men
      with whom they can engage in unprotected sex. Data collection was conducted via
      telephone interviews between January 2008 and May 2009. Structural equation
      analysis was undertaken to examine the specific nature of the relationships
      involved in understanding HIV risk practices. RESULTS: Emotional neglect was
      highly prevalent among the men participating in this study. Emotional neglect
      experiences were not found to be related directly to involvement in HIV risk
      taking in adulthood. Emotional neglect, was found to be an important variable in
      the overall structural equation. Its effect on HIV risk taking was indirect,
      operating principally by having a negative impact upon self-esteem, which in turn
      had a negative effect on attitudes toward condom use, which in turn were related
      strongly and directly to risk taking. CONCLUSIONS: Childhood experiences with
      emotional neglect are relevant to understanding HIV risk practices among MSM in
      adulthood, but the relationship is not as simple as usually conceptualized.
      Rather, emotional neglect appears to impact risk taking indirectly, through its
      effects on mental health functioning, which in turn affects risk-related
      attitudes.

PMID- 24456743
TI  - Longitudinal patterns of physical activity in children aged 8 to 12 years: the
      LOOK study.
AB  - BACKGROUND: Data on longitudinal monitoring of daily physical activity (PA)
      patterns in youth over successive years is scarce but may provide valuable
      information for intervention strategies aiming to promote PA. METHODS:
      Participants were 853 children (starting age ~8 years) recruited from 29
      Australian elementary schools. Pedometers were worn for a 7-day period each year
      over 5 consecutive years to assess PA volume (steps per day) and accelerometers
      were worn concurrently in the final 2 years to assess PA volume (accelerometer
      counts (AC) per day), moderate and vigorous PA (MVPA), light PA (LPA) and
      sedentary time (SED). A general linear mixed model was used to examine daily and
      yearly patterns. RESULTS: A consistent daily pattern of pedometer step counts,
      AC, MVPA and LPA emerged during each year, characterised by increases on school
      days from Monday to Friday followed by a decrease on the weekend. Friday was the
      most active and Sunday the least active day. The percentage of girls and boys
      meeting international recommendations of 11,000 and 13,000 steps/day respectively
      on a Monday, Friday and Sunday were 36%, 50%, 21% for boys and 35%, 45%, 18% for
      girls. The equivalent percentages meeting the recommended MVPA of >60 min/day on
      these days were 29%, 39%, 16% for boys and 15%, 21%, 10% for girls. Over the 5
      years, boys were more active than girls (mean steps/day of 10,506 vs 8,750;
      p<0.001) and spent more time in MVPA (mean of 42.8 vs 31.1 min/day; p<0.001).
      Although there was little evidence of any upward or downward trend in steps/day
      from age 8 to 12 years, there was a trend toward lower MVPA, LPA and a
      corresponding increase in SED from age 11 to 12 years. CONCLUSION: A weekly
      pattern of PA occurred in children as young as age 8 on a day by day basis; these
      patterns persisting through to age 12. In addition to supporting previous
      evidence of insufficient PA in children, our data, in identifying the level and
      incidence of insufficiency on each day of the week, may assist in the development
      of more specific strategies to increase PA in community based children.

PMID- 24456744
TI  - Designer psychostimulants: pharmacology and differences.
AB  - More than 200 novel psychoactive drugs have been reported in Europe, with 73
      added in 2012 and additional compounds encountered every week in 2013. Many of
      these are "designer psychostimulants" which aim to mimic the subjective effects
      of amphetamines, cocaine or 3,4-methylenedioxymethylamphetamine (MDMA;
      "Ecstasy"). Several drugs are based on the beta-ketoamphetamine cathinone
      chemical structure, others include aminoindanes, aminotetralins, piperazines,
      amphetamine analogues and pipradrol derivatives. Although a detailed analysis of
      the pharmacology of these novel drugs is largely lacking, a number of scientific
      studies have been reported in 2011-2013 and these are reviewed. All of the novel
      psychostimulants activate monoamine systems in the brain - with differing
      dopamine (DA) v serotonin (5-HT) preferences. Those activating principally DA
      systems are amphetamine-like stimulants, such as naphyrone, desoxypipradrol, 3,4
      methylenedioxypyrovalerone (MDPV), and benzylpiperazine while those
      preferentially activating 5-HT mechanisms are MDMA-like or cocaine-like
      stimulants, such as mephedrone, methylone and other substituted cathinones,
      aminoindanes, aminotetralins and piperazines. The ability of mephedrone and other
      novel psychostimulants to substitute for methylamphetamine or cocaine in drug
      discrimination tests in rats, and the ability of mephedrone to induce conditioned
      place preference and to sustain self-administration behaviour suggests that this
      and other cocaine/methylamphetamine-like drugs have dependence liability. This
      article is part of the Special Issue entitled 'CNS Stimulants'. 

PMID- 24456745
TI  - Significance of higher-order chromatin architecture for neuronal function and
      dysfunction.
AB  - Recent studies in neurons indicate that the large-scale chromatin architectural
      framework, including chromosome territories or lamina-associated chromatin,
      undergoes dynamic changes that represent an emergent level of regulation of
      neuronal gene-expression. This phenomenon has been implicated in neuronal
      differentiation, long-term potentiation, seizures, and disorders of neural
      plasticity such as Rett syndrome and epilepsy.

PMID- 24456746
TI  - Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Abeta1-42
      induced memory impairment and neuroinflammatory and apoptotic responses in mice.
AB  - Montelukast, known as a cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is
      currently used for treatment of inflammatory diseases such as asthma. Here, we
      investigated effects of montelukast on neuroinflammatory, apoptotic responses,
      and memory performance following intracerebral infusions of amyloid-beta (Abeta).
      The data demonstrated that intracerebroventrical infusions of aggregated Abeta1
      42 (410 pmol/mouse) produced deficits in learning ability and memory, as
      evidenced by increase in escape latency during acquisition trials and decreases
      in exploratory activities in the probe trial in Morris water maze (MWM) task, and
      by decrease in the number of correct choices and increase in latency to enter the
      shock-free compartment in Y-maze test, and caused significant increases in pro
      inflammatory cytokines such as NF-kappaB p65, TNF-alpha and IL-1beta as well as
      pro-apoptotic molecule caspase-3 activation and anti-apoptotic protein Bcl-2
      downregulation in hippocampus and cortex. Interestingly, this treatment resulted
      in upregulation of protein or mRNA of CysLT1R in both hippocampus and cortex.
      Blockade of CysLT1R by repeated treatment with montelukast (1 or 2 mg/kg, ig, 4
      weeks) reduced Abeta1-42-induced CysLT1R expression and also suppressed Abeta1-42
      induced increments of NF-kappaB p65, TNF-alpha, IL-1beta and caspase-3
      activation, and Bcl-2 downregulation in the hippocampus and cortex.
      Correspondingly, montelukast treatment significantly improved Abeta1-42-induced
      memory impairment in mice, but had little effect on normal mice. Our results show
      that montelukast may ameliorate Abeta1-42-induced memory impairment via
      inhibiting neuroinflammation and apoptosis mediated by CysLT1R signaling,
      suggesting that CysLT1R antagonism represents a novel treatment strategy for
      Alzheimer's disease. 

PMID- 24456747
TI  - Long-term treatment with l-DOPA and an mGlu5 receptor antagonist prevents changes
      in brain basal ganglia dopamine receptors, their associated signaling proteins
      and neuropeptides in parkinsonian monkeys.
AB  - Brain glutamate overactivity is well documented in Parkinson's disease (PD) and
      antiglutamatergic drugs decrease L-3,4-dihydroxyphenylalanine (l-DOPA)-induced
      dyskinesias (LID); the implication of dopamine neurotransmission is not
      documented in this anti-LID activity. Therefore, we evaluated changes of dopamine
      receptors, their associated signaling proteins and neuropeptides mRNA, in normal
      control monkeys, in saline-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-lesioned monkeys and in L-DOPA-treated MPTP monkeys, without or with an
      adjunct treatment to reduce the development of LID: 2-methyl-6
      (phenylethynyl)pyridine (MPEP), the prototypal metabotropic glutamate 5 (mGlu5)
      receptor antagonist. All de novo treatments were administered for 1 month and the
      animals were sacrificed thereafter. MPTP monkeys treated with l-DOPA + MPEP
      developed significantly less LID than MPTP monkeys treated with l-DOPA alone.
      [(3)H]SCH-23390 specific binding to D1 receptors of all MPTP monkeys was
      decreased as compared to controls in the basal ganglia and no difference was
      observed between all MPTP groups, while striatal D1 receptor mRNA levels remained
      unchanged. [(3)H]raclopride specific binding to striatal D2 receptors and mRNA
      levels of D2 receptors were increased in MPTP monkeys compared to controls; l
      DOPA treatment reduced this binding in MPTP monkeys while it remained elevated
      with the l-DOPA + MPEP treatment. Striatal [(3)H]raclopride specific binding
      correlated positively with D2 receptor mRNA levels of all MPTP-lesioned monkeys.
      Striatal preproenkephalin/preprodynorphin mRNA levels and phosphorylated ERK1/2
      and Akt/GSK3beta levels increased only in L-DOPA-treated MPTP monkeys as compared
      to controls, saline treated-MPTP and l-DOPA + MPEP treated MPTP monkeys. Hence,
      reduction of development of LID with MPEP was associated with changes in D2
      receptors, their associated signaling proteins and neuropeptides. 

PMID- 24456748
TI  - Mapping of neurotrophins and their receptors in the adult mouse brain and their
      role in the pathogenesis of a transgenic murine model of bovine spongiform
      encephalopathy.
AB  - Neurotrophins are a family of growth factors that act on neuronal cells. The
      neurotrophins include nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF) and neurotrophin (NT)-3, -4 and -5. The action of neurotrophins
      depends on two transmembrane-receptor signalling systems: (1) the tropomyosin
      related kinase (Trk) family of tyrosine kinase receptors (Trk A, Trk B and Trk C)
      and (2) the p75 neurotrophin receptor (p75(NTR)). The interaction between
      neurotrophic factors and their receptors may be involved in the mechanisms that
      regulate the differential susceptibility of neuronal populations in
      neurodegenerative diseases. The aim of the present study was to evaluate the role
      of neurotrophins in the pathogenesis of bovine spongiform encephalopathy (BSE)
      using a transgenic mouse overexpressing bovine prnp (BoTg 110). Histochemistry
      for Lycopersicum esculentum agglutinin, haematoxylin and eosin staining and
      immunohistochemistry for the abnormal isoform of the prion protein (PrP(d)),
      glial fibrillary acidic protein (GFAP), NGF, BDNF, NT-3 and the receptors Trk A,
      Trk B, Trk C and p75(NTR) was performed. The lesions and the immunolabelling
      patterns were assessed semiquantitatively in different areas of the brain. No
      significant differences in the immunolabelling of neurotrophins and their
      receptors were observed between BSE-inoculated and control animals, except for
      p75(NTR), which showed increased expression correlating with the distribution of
      lesions, PrP(d) deposition and gliosis in the BSE-inoculated mice. 

PMID- 24456749
TI  - Peripheral neuroblastomas in dogs: a case series.
AB  - The peripheral neuroblastic tumours (PNTs) include neuroblastoma,
      ganglioneuroblastoma and ganglioneuromas. These subtypes reflect a spectrum of
      differentiation of progenitor cells of the sympathetic nervous system from
      tumours with predominant undifferentiated neuroblasts to those consisting of
      neuronal cell bodies that are well differentiated. Peripheral neuroblastoma is a
      tumour composed of neuroblastic cells with no or limited neuronal
      differentiation. In dogs, peripheral neuroblastoma is rare. The present report
      documents nine cases of canine peripheral neuroblastoma, the majority occurring
      as large masses in the craniodorsal abdominal cavity of young dogs (mean age of 3
      years at diagnosis). Microscopically, all of the masses consisted of round to
      oval cells with a scant cytoplasm and hyperchromatic nuclei. Homer-Wright
      rosettes and pseudorosettes were evident in three of the nine cases. Neoplastic
      cells were immunoreactive in varying degrees to S100, neuron-specific enolase,
      synaptophysin, chromogranin A, tyrosine hydroxylase (one case) and were negative
      for vimentin, cytokeratin, CD3 and CD79a, indicating a neurogenic nature. Four of
      the nine cases occurred in Labrador retrievers (44%) and two (22%) in boxers,
      suggesting a possible breed predisposition.

PMID- 24456750
TI  - A histopathological study of bovine ganglia.
AB  - One hundred and sixty-eight ganglia from 54 cattle aged 10 days to 10 years were
      examined microscopically. Samples from six autonomic ganglia and one sensory
      ganglion were represented. Thirteen animals were clinically normal and 41 were
      submitted for post-mortem examination. Neuronal vacuolation, spheroid formation,
      lipofuscin accumulation and central chromatolysis were observed sporadically and
      were of varying magnitude. Neuronal vacuolation and spheroid formation were not
      age-related changes, while lipofuscin accumulation was more common in older
      animals and central chromatolysis was more common in younger cattle. Non
      suppurative inflammation and neuronophagia were also common findings (23 out of
      54 animals, 42.6%) in autonomic ganglia that did not contain herpesvirus DNA as
      determined by polymerase chain reaction. Renaut bodies, features of peripheral
      nerves, were most commonly noted in the vagus. None of the histopathological
      findings were related to any particular disease in which loss of autonomic
      nervous system function might be expected. Furthermore, all changes were as
      common in clinically normal animals as in animals with disease. 

PMID- 24456752
TI  - Single-incision video-assisted thoracic resection for extrapulmonary
      sequestration: a case report.
AB  - We describe surgical resection of an extralobar pulmonary sequestration via
      single-incision thoracoscopic surgery (SITS), which we recommend as a suitable
      surgical option. A 45-year-old Japanese woman was admitted to our hospital for
      further examination of chest abnormal shadow. A rigid 5-mm 30 degrees  video
      thoracoscope, an endograsper and an electric cautery were passed within the same
      single small incision. The tumor was suspended using articulating endograspers
      and resected after clipping and ligation of the anomalous vessel. The final
      pathology was determined an extrapulmonary sequestration. 

PMID- 24456753
TI  - Central nervous system effects and chemical composition of two subspecies of
      Agastache mexicana; an ethnomedicine of Mexico.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Agastache mexicana subspecies mexicana (Amm) and
      xolocotziana (Amx) are used in Mexican traditional medicine to relief cultural
      affiliation syndromes known as "susto" or "espanto", for "nervous" condition, and
      as a sleep aid. Despite its intensive use, neuropharmacological studies are
      scarce, and the chemical composition of the aqueous extracts has not been
      described. Aims of the study are: (1) To analyze the chemical composition of
      aqueous extracts from aerial parts of Amm and Amx. (2) To evaluate the anxiolytic
      like, sedative, antidepressant-like effects. (3) Analyze the general toxic
      effects of different doses. MATERIALS AND METHODS: Anxiolytic-like and sedative
      effects were measured in the avoidance exploratory behavior, burying behavior and
      the hole-board tests. The antidepressant-like actions were studied in the forced
      swimming and tail suspension tests. Finally, general activity and motor
      coordination disturbances were evaluated in the open field, inverted screen and
      rota-rod tests. The acute toxicity of Amm and Amx was determined by calculating
      their LD50 (mean lethal dose). The chemical analyses were performed employing
      chromatographic, photometric and HPLC-ESI-MS techniques. RESULTS: Low doses of
      Amm and Amx (0.1sigma1.0mg/kg) induced anxiolytic-like actions; while higher
      doses (over 10mg/kg) induced sedation and reduced the locomotor activity,
      exerting a general inhibition in the central nervous system (CNS). CONCLUSIONS:
      Results support the use of Amm and Amx in traditional medicine as tranquilizers
      and sleep inducers. Additionally, this paper contributes to the knowledge of the
      chemical composition of the aqueous extracts of these plants.

PMID- 24456754
TI  - Time to positivity in liquid culture predicts colony forming unit counts of
      Mycobacterium tuberculosis in sputum specimens.
AB  - Time to liquid culture positivity (TTP) is a technically accessible and widely
      available measure of viable mycobacterial load in sputum samples. We describe the
      ability of TTP to predict colony forming unit counts of Mycobacterium
      tuberculosis from sputum samples collected before or during the first 14 days of
      antituberculosis therapy. 

PMID- 24456755
TI  - Human umbilical cord mesenchymal stromal cells in regenerative medicine.
AB  - Cells of the human umbilical cord offer tremendous potential for improving human
      health. Cells from the Wharton's jelly (umbilical cord stroma) in particular,
      referred to as human umbilical cord mesenchymal stromal cells (HUCMSCs), hold
      several advantages that make them appealing for translational research. In the
      previous issue of Stem Cell Research & Therapy, Chon and colleagues made an
      important contribution to the HUCMSC literature not only by presenting HUCMSCs as
      an emerging cell source for intervertebral disc regeneration in general and the
      nucleus pulposus in particular, but also by demonstrating that an extracellular
      matrix-based strategy might be preferred over the use of growth factors. By
      culturing HUCMSCs under hypoxia in serum-free conditions in the presence of
      Matrigel with laminin-111, they were able to achieve intense collagen II staining
      by 21 days without the addition of exogenous growth factors. There is tremendous
      translational significance here in that such raw materials may alleviate the need
      for the use of growth factors in some instances, and this may have important
      ramifications in reducing product cost and streamlining regulatory approval. Chon
      and colleagues provide a promising example of the potential of HUCMSCs,
      demonstrating the ability to guide HUCMSC differentiation even in the absence of
      serum and growth factors and supporting the use of HUCMSCs as a viable
      alternative in intervertebral disc regeneration.

PMID- 24456756
TI  - Socioeconomic factors associated with trajectories of caring by young and mid
      aged women: a cohort study.
AB  - BACKGROUND: The health and socioeconomic outcomes from being a caregiver are well
      described. In contrast, the long-term trajectories of caring undertaken by women,
      and the demographic, socioeconomic status, health status and health behaviour
      characteristics associated with these trajectories is not well known. METHODS:
      The data were from the Australian Longitudinal Study on Women's Health.
      Participants were 14,202 women born 1973-78 followed for 13 years, and 12,282
      women born 1946-1951 followed for 9 years. Latent class analyses and multinomial
      logistic regression were used. RESULTS: Five distinct trajectories of caring were
      identified for the younger women: these represented 'ongoing', 'starting',
      'never' and 2 types of 'transitional' caring. While traditional indicators of
      poorer socioeconomic status were associated with trajectories representing
      'ongoing' and 'starting' caring, they were not associated with 'transitional'
      caring trajectories. Three distinct trajectories of caring were identified for
      the mid-age women: these represented 'ongoing', 'starting' and 'never' caring.
      For the mid-age women, poorer socioeconomic status indicators were associated
      with the 'ongoing' caring, but not 'starting' caring. CONCLUSIONS: Women in the
      1973-78 cohort showed more varying and transitional caring trajectories compared
      to those in the 1946-51 cohort, and these trajectories were not associated with
      traditional socioeconomic indicators. An 'opportunity cost' theory for who become
      carers does not support young transitional carers or mid-aged women beginning new
      caring. Health policies, education and awareness campaigns for women carers need
      to target outside previously identified populations.

PMID- 24456757
TI  - HIV-1 virologic failure and acquired drug resistance among first-line
      antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross
      sectional study.
AB  - BACKGROUND: An increasing number of people on antiretroviral therapy (ART) in sub
      Saharan Africa has led to declines in HIV related morbidity and mortality.
      However, virologic failure (VF) and acquired drug resistance (ADR) may negatively
      affect these gains. This study describes the prevalence and correlates of HIV-1
      VF and ADR among first-line ART experienced adults at a rural HIV clinic in
      Coastal Kenya. METHODS: HIV-infected adults on first-line ART for >=6 months were
      cross-sectionally recruited between November 2008 and March 2011. The primary
      outcome was VF, defined as a one-off plasma viral load of >=400 copies/ml. The
      secondary outcome was ADR, defined as the presence of resistance associated
      mutations. Logistic regression and Fishers exact test were used to describe
      correlates of VF and ADR respectively. RESULTS: Of the 232 eligible participants
      on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 - 30.6])
      had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of
      these, 29 (52.7% [95% CI: 38.8 - 66.3]) had at least one ADR, with 25 samples
      having dual-class resistance mutations. The most prevalent ADR mutations were the
      M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55
      successfully amplified viraemic samples (47.3%) did not have any detectable
      resistance mutation. Younger age (15-34 vs. >=35 years: adjusted odd ratios [95%
      CI], p-value: 0.3 [0.1-0.6], p = 0.002) and unsatisfactory adherence (<95% vs.
      >=95%: 3.0 [1.5-6.5], p = 0.003) were strong correlates of VF. Younger age,
      unsatisfactory adherence and high viral load were also strong correlates of ADR.
      CONCLUSIONS: High levels of VF and ADR were observed in younger patients and
      those with unsatisfactory adherence. Youth-friendly ART initiatives and
      strengthened adherence support should be prioritized in this Coastal Kenyan
      setting. To prevent unnecessary/premature switches, targeted HIV drug resistance
      testing for patients with confirmed VF should be considered.

PMID- 24456758
TI  - Micro- and nanotopography with extracellular matrix coating modulate human
      corneal endothelial cell behavior.
AB  - The human corneal endothelium plays an important role in maintaining corneal
      transparency. Human corneal endothelial cells have limited regenerative
      capability in vivo. Consequently, endothelial dysfunction can occur following
      corneal endothelial trauma or inherited diseases. To restore endothelial
      function, corneal transplantation is needed. However, there is a worldwide
      shortage of donor corneas, motivating the development of a tissue-engineered
      graft alternative using cultivated endothelial cells. To induce in vitro cell
      proliferation, much effort has been made to improve culture conditions and to
      mimic the native extracellular microenvironment. We incorporated topographical
      and biochemical cues in our in vitro culture of human corneal endothelial cell
      line B4G12 (HCEC-B4G12) and hypothesized that manipulation of the extracellular
      environment can modulate cell proliferation, morphometry and phenotype. The
      topographies tested were nanopillars, microwells and micropillars on
      polydimethylsiloxane, while the biochemical factors were extracellular matrix
      protein coatings of fibronectin-collagen I (FC), FNC(r) coating mix (FNC) and
      laminin-chondroitin sulfate (LC). Cellular morphometry, Na(+)/K(+)-ATPase and
      zona occludens 1 (ZO-1) gene and protein expression were analyzed 3days after
      cells had formed a confluent monolayer. The cell circularity on all patterns and
      coatings was above 0.78. On all coatings, cell area was the lowest on
      micropillars. The coefficient of variation (CV) of the cell area was the lowest
      on nanopillars with an LC coating. With an FC coating, micropillars induced a
      better cellular outcome as the cells had the greatest circularity, smallest cell
      area and highest Na(+)/K(+)-ATPase and ZO-1 gene and protein expression. With the
      LC coating, HCECs grown on nanopillars resulted in the lowest CV of the cell area
      and the highest ZO-1 gene expression. Thus, HCEC-B4G12 morphometry and phenotype
      can be improved using different topographical and biochemical cues. 

PMID- 24456759
TI  - A collagen-hydroxyapatite scaffold allows for binding and co-delivery of
      recombinant bone morphogenetic proteins and bisphosphonates.
AB  - An emerging paradigm in orthopedics is that a bone-healing outcome is the product
      of the anabolic (bone-forming) and catabolic (bone-resorbing) outcomes. Recently,
      surgical and tissue engineering strategies have emerged that combine recombinant
      human bone morphogenetic proteins (rhBMPs) and bisphosphonates (BPs) in order to
      maximize anabolism and minimize catabolism. Collagen-based scaffolds that are the
      current surgical standard can bind rhBMPs, but not BPs. We hypothesized that a
      biomimetic collagen-hydroxyapatite (CHA) scaffold would bind both agents and
      produce superior in vivo outcomes. Consistent with this concept, in vitro elution
      studies utilizing rhBMP-2 ELISA assays and scintillation counting of (14)C
      radiolabeled zoledronic acid (ZA) confirmed delayed release of both agents from
      the CHA scaffold. Next, scaffolds were tested for their capacity to form ectopic
      bone after surgical implantation into the rat hind limb. Using CHA, a significant
      6-fold increase in bone volume was seen in rhBMP-2/ZA groups compared to rhBMP-2
      alone, confirming the ability of ZA to enhance rhBMP-2 bone formation. CHA
      scaffolds were found to be capable of generating mineralized tissue in the
      absence of rhBMP-2. This study has implications for future clinical treatments of
      critical bone defects. It demonstrates the relative advantages of co-delivering
      anabolic and anti-catabolic agents using a multicomponent scaffold system. 

PMID- 24456760
TI  - Grammont reversed prosthesis for acute complex fracture of the proximal humerus
      in an elderly population with 5 to 12 years follow-up.
AB  - PURPOSE OF THE STUDY: The aim of this retrospective study was to analyze outcome
      in 23 cases of Delta III reverse ball-and-socket total shoulder prosthesis
      implantation for acute complex fractures of the proximal humerus in an elderly
      population with poor bone quality. In this type of population, this procedure
      could respond to the difficulties of a reliable and efficient re-fixation of the
      tubercles. MATERIAL AND METHODS: From 1993 to 2000, 23 Delta III prostheses were
      implanted by a single operator for acute injury: 18 three-part and four-part
      fractures and five fracture-dislocations. The study population included two men
      and 21 women, mean age 75 years, ten on the dominant side. Surgery was performed
      under general anesthesia in the semi-sitting position via the anterolateral
      approach without osteotomy of the acromion, with 10-20 degrees  retroversion of
      the humeral stem (except in one shoulder) and cement fixation in two. For five
      shoulders, the tubercles were re-fixed. Postoperative physiotherapy was not
      possible in all patients. Outcome was assessed with the Constant score and with
      AP and lateral Lamy radiographs. RESULTS: Seven patients died so the series
      included 16 cases for analysis. Complications were: reflex sympathetic dystrophy
      (n=2), postoperative Acinetobacter infection (n=1) requiring revision to clean
      and drain allowing preservation of the prosthesis, and early postoperative
      anterior dislocation (n=1) (10 degrees  stem anteversion) with surgical revision
      to re-orient the stem. At a mean follow-up of 86 months, the Constant score was
      60 points (contralateral shoulder, 83 points). Outcome, influenced in cases of re
      fixation of the tubercles, was good for pain (14.1), activity (13.3), strength
      (16.1), anterior elevation (6.5), and abduction (6.5), but very poor for external
      (1.1) and internal (2.4) rotation. The radiographs showed aseptic glenoid
      loosening (n=1) at 12 years with surgical revision in 2005; the Constant score at
      6 months follow-up was 48 points, inferior scapular notching (n=11) according the
      Nerot classification (six stage 1, four stage 2, one stage 3, at 2, 4.3, and 5
      years follow-up), inferior spurs (n=9) appearing at a mean 2.5 years follow-up
      (stable after emergence without clinical impact), proximal humeral resorption
      (n=4) (medially for three at a mean 8 years follow-up and one laterally at 10
      years), and a humeral radiolucent line (n=1) at 5 years follow-up. DISCUSSION:
      For acute complex fractures of the proximal humerus in elderly subjects with poor
      bone quality, when effective and reliable re-fixation of the tubercles is
      difficult or impossible, the reverse ball-and-socket shoulder prosthesis is a
      possible alternative providing good functional outcome except for rotations, but
      with the risk of inferior scapular notching. Although not problematic in the
      medium term, these notches may contribute to glenoid loosening with bone loss in
      the long term. Nevertheless, this procedure seems to improve the status of
      patients with such fractures.

PMID- 24456761
TI  - Unstable fractures of the spine. Surgical methods. Synthesis of the injured dorso
      lumbar spine by plates screwed into vertebral pedicles.

PMID- 24456762
TI  - Pathogeny and natural history of congenital dislocation of the hip.
AB  - Based on a review of the literature, the authors have made a critical study of
      several etiological factors. Endogenous factors such as acetabular dysplasia,
      increased anteversion of the femoral neck, and capsular laxity support the
      genetic theory but are neither constant nor necessary and are only facilitating
      factors. The major factor seems to be a mechanical one linked to the position in
      the uterus: hyperflexion with adduction and external rotation constituting the
      dislocating foetal posture combined with abnormal pressure on the greater
      trochanter and leading to expulsion of the head upward and backward. This theory
      can explain the natural history of C D H which is first, at birth a hip
      instability followed by two possible evolutions: either persistent luxation
      becoming irreducible or spontaneous stabilisation leading sometimes to complete
      healing or to residual abnormalities (subluxation or dysplasia). This concept
      suggests practical conclusions: the importance of an early diagnosis, the
      selection of the signs of the hip at risk, the pattern of prevention, the role
      for non-clinical investigations, the principles of the treatment based on
      postures, the indications for the different types of treatment. 

PMID- 24456763
TI  - GUEPAR hinge knee prosthesis.
AB  - Early and late results of the GUEPAR hinge knee prosthesis were evaluated on a
      series of 184 operations performed before January 1st, 1974. There were 3
      immediate deaths and 26 before 5 years. Nineteen prostheses were removed. One
      hundred and twenty-six knees had degenerative osteoarthritis, 52 rheumatoid
      arthritis. Twenty-two had been operated on before. Patellar displacement, present
      in 27% of the cases, was the most frequent cause of complaint: pain or
      instability, proportional to the severity of displacement, made re-operation
      necessary in 10% of the patients. Addition of a patellar prosthesis was the most
      successful treatment as far as pain is concerned: it is probably advisable as a
      primary procedure. Deep infections occurred in 8.3% of the cases, infrequently
      after 2 years. Healing was obtained in all cases either by revision or by removal
      and arthrodesis: but functional results were poor except when fusion was
      achieved, in half of the cases of arthrodesis. Loosening occurred in 16% of the
      cases, mainly as a consequence of inadequate technique. It was frequently
      tolerated: re-operation was necessary in 6% of the total. Late functional results
      were evaluated in 99 cases with a follow-up of 5 to 8 years. Apart from
      loosening, the results did not deteriorate. Sixty percent were evaluated as
      excellent or good, 29% fair, and 11% poor. In consideration of these results, the
      choice of this prosthesis should be limited to special cases. To prevent
      complications, the use of a patellar prosthesis, of reinforced models and of
      cementing under pressure is advisable.

PMID- 24456764
TI  - Femoral and tibial bone torsions associated with medial femoro-tibial
      osteoarthritis. Index of cumulative torsions.
AB  - Frontal plane varus deviation is one of the mechanisms hypothesized to be
      involved in the pathogenesis of medial compartment osteoarthritis of the knee.
      But only a few authors have suggested a role for tibial and femoral torsion. In
      the current study, CT scan was used to measure bone torsion. The torsional
      morphology of the lower limb was defined by the "index of cumulative torsions"
      (ICT). The resulting values were compared to the frontal angular deviation data.
      The effects of tibial and femoral torsion on the position of the lower limb
      during the stance phase of walking and the consequences for the knee are
      discussed. 

PMID- 24456765
TI  - Ligamentoplasty using the peroneus brevis in the treatment of chronic
      instabilities of the ankle. Long-term review.
AB  - Sixteen cases in which a ligamentoplasty using the peroneus brevis were followed
      up for more than 8 years. In half of the cases, dorsiflexion of the ankle was
      diminished and the subtalar joint was stiff. There was no anterior drawer sign of
      the talus. No case of progressive degenerative arthritis of the ankle joint was
      seen.

PMID- 24456766
TI  - Total arthroplasty of the hip by fritted alumina prosthesis. Experimental study
      and 1st clinical applications.
AB  - A new material is proposed in total hip arthroplasty as a bearing component. The
      tolerance of dense ceramics was studied, as well as the anchorage of this
      material into bone. Physical, chemical and mechanical properties of the
      prosthesis were tested. Two hundred patients have already been operated on, but
      the follow-up is too short for any conclusion. 

PMID- 24456767
TI  - Gamma nail in the treatment of closed trochanteric fractures. Results and
      indications of 121 cases.
AB  - The Gamma Nail is the latest advance in the treatment of trochanteric fractures
      based on intramedullary nailing principles during closed procedures. Its design
      is based on Kuntscher's Y-nail and locking intramedullary (IM) nails. This paper
      reports the results from the first-ever series of 121 patients operated between
      1988 and 1990. They were followed until bone union was achieved. The mean patient
      age was 75 years. Most patients were in poor general health and had unstable
      fractures. Anatomical preoperative reduction was achieved in 72% of cases.
      Fixation was good in 66% of cases and acceptable in 27% of cases. Intra-operative
      complications consisted of nine fractures without consequences. Of the treated
      patients, 83.4% resumed weight-bearing during the first week. There was one case
      of deep infection that resolved with treatment. The mortality rate was 12.3% at
      three months. We noted 7 alunions in varus, 3 in valgus, 2 in external rotation
      and 1 in internal rotation. There were no cases of non-union. In six cases, the
      screw had cut out of the femoral head. The drawbacks associated with surgical
      treatment methods for trochanteric fractures also apply to the Gamma nail.
      Nevertheless, one of its primary advantages is the possibility of using a closed
      procedure. When compared to Ender nailing, knee pain is absent and weight-bearing
      can be achieved in all patients, no matter the fracture type.

PMID- 24456769
TI  - Radical prostatectomy: biochemical recurrence and prognostic factors.

PMID- 24456768
TI  - Changes in the microbial communities during co-composting of digestates.
AB  - Anaerobic digestion is a waste treatment method which is of increasing interest
      worldwide. At the end of the process, a digestate remains, which can gain added
      value by being composted. A study was conducted in order to investigate microbial
      community dynamics during the composting process of a mixture of anaerobic
      digestate (derived from the anaerobic digestion of municipal food waste), green
      wastes and a screened compost (green waste/kitchen waste compost), using the
      COMPOCHIP microarray. The composting process showed a typical temperature
      development, and the highest degradation rates occurred during the first 14 days
      of composting, as seen from the elevated CO2 content in the exhaust air. With an
      exception of elevated nitrite and nitrate levels in the day 34 samples, physical
      chemical parameters for all compost samples collected during the 63 day process
      indicated typical composting conditions. The microbial communities changed over
      the 63 days of composting. According to principal component analysis of the
      COMPOCHIP microarray results, compost samples from the start of the experiment
      were found to cluster most closely with the digestate and screened compost
      samples. The green waste samples were found to group separately. All starting
      materials investigated were found to yield fewer and lower signals when compared
      to the samples collected during the composting experiment.

PMID- 24456770
TI  - Controversial predictors of biochemical recurrence after radical prostatectomy: a
      study from a Latin American (Brazilian) institution.
AB  - PURPOSE: To analyze controversial clinicopathologic predictors of biochemical
      recurrence after surgery: age, race, tumor extent on surgical specimen, tumor
      extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of
      extraprostatic extension and positive surgical margins. MATERIALS AND METHODS:
      The needle biopsies and the correspondent surgical specimens were analyzed from
      400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and
      risk of shorter time to recurrence using Cox univariate and multivariate
      analysis. RESULTS: Except for age, race, maximum percentage of cancer per core,
      and number of cores with cancer, all other variables studied were significantly
      predictive of time to biochemical recurrence using the Kaplan-Meier curves. In
      univariate analysis, except for focal extraprostatic extension, age, race, focal
      positive surgical margins, and maximum extent and percentage of cancer per core,
      all other variables were significantly predictive of shorter time to recurrence.
      On multivariate analysis, diffuse positive surgical margins and preoperative PSA
      were independent predictors. CONCLUSIONS: Young patients and non-whites were not
      significantly associated with time to biochemical recurrence. The time consuming
      tumor extent evaluation in surgical specimens seems not to add additional
      information to other well established predictive findings. The higher predictive
      value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4
      as the predominant pattern. Extent and not simply presence or absent of
      extraprostatic extension should be informed. Most tumor extent evaluations on
      needle biopsies are predictive of time to biochemical recurrence, however,
      maximum percentage of cancer in all cores was the strongest predictor.

PMID- 24456771
TI  - Serum levels of sex hormone binding globulin (SHBG) are not predictive of
      prostate cancer diagnosis and aggressiveness: results from an Italian biopsy
      cohort.
AB  - PURPOSE: To explore the association between serum levels of Sex Hormone Binding
      Globulin (SHBG) and the risk of developing prostate cancer (PCa) as well as high
      grade disease in men undergoing prostate biopsy. MATERIALS AND METHODS: Between
      2006 and 2012, we prospectively enrolled 740 patients with no history of PCa
      undergoing prostate biopsy. Before biopsy general data of the patient DRE, PSA
      and BMI were recorded. The risk of detecting cancer and high grade cancer was
      assessed as a function of SHBG using crude and adjusted logistic regressions.
      RESULTS: Serum levels of SHBG were not associated with an increased risk of PCa
      or high grade disease. Age (OR 1.027 95% CI 1.003-1.052 p = 0.027), DRE (OR 3.391
      95% CI 2.258-5.092 p = 0.000) and PSA (OR 1.078 95% CI 1.037-1.120 p = 0.000)
      were found to be independent predictors of prostate cancer risk. Age (OR 1.051
      95% CI 1.009-1.095 p = 0.016), DRE (OR 2.519 95% CI 1.384-4.584 p = 0.000), BMI
      (OR 1.098 95% CI 1.011-1.193 p = 0.027) and PSA (OR 1.074 95% CI 1.014-1.137 p =
      0.015) were found to be independent predictors of high grade disease.
      CONCLUSIONS: In our cohort of patients, serum levels of SHBG are not predictive
      of PCa or high grade disease. According to our experience SHBG should not be
      considered a biomarker in PCa diagnosis neither a marker for high grade disease.

PMID- 24456772
TI  - Can single positive core prostate cancer at biopsy be considered a low-risk
      disease after radical prostatectomy?
AB  - PURPOSE: Single positive core in a prostate biopsy is usually associated with
      indolent prostate cancer (PCa) and is one of the active surveillance (AS)
      inclusion criteria. We investigated whether single positive core PCa at biopsy
      could define an archetype of low-risk disease. MATERIALS AND METHODS: A total of
      1320 consecutive patients were enrolled. Among them, 249 patients with single
      positive core PCa were followed up, and the clinical and pathological parameters
      influencing prognosis were analyzed. RESULTS: Out of the 249 patients, 172
      (69.0%) had pathological findings >= pT2c and 87 (34.9%) had an undergraded
      Gleason Score (GS) based on the biopsy. Positive surgical margins (PSMs),
      extraprostatic extension (EPE) and seminal vesicle invasion (SVI) were found in
      20.8%, 10.0% and 6.0% of patients, respectively. In a comparative analysis, we
      found that the PSA level, prostate weight and number of cores at biopsy are
      essential to correctly predict an indolent PCa. A total of 125 patients (67.3%)
      with nonpalpable tumors became high-risk tumors (pT2c-T3). Analyzing only
      nonpalpable tumors with a GS of 6 at biopsy (156 patients), we noted that 106
      (67.9% of cT1) progressed from cT1c to pT2c-pT3. CONCLUSIONS: Single core PCa
      have clinically significant disease in the Radical Prostatectomy specimens, with
      considerable rates of overgrading for the GS, pT2c-pT3, PSMs, EPE and SVI. The
      treatment plan must be evaluated individually for patients with single core PCa
      and must take into account other prognostic factors when determining whether a
      patient should be managed with AS.

PMID- 24456773
TI  - The efficacy of hemostatic radiotherapy for bladder cancer-related hematuria in
      patients unfit for surgery.
AB  - OBJECTIVE: The aim of our study was to assess short and mid-term clinical
      efficacy of external beam radiation therapy to achieve hemostasis in patients
      with bladder-cancer related gross hematuria who were unfit for surgery. We also
      assessed hypofractionation as a possible alternative option for more severe
      patients. PATIENTS AND METHODS: Thirty-two patients were included for hemostatic
      radiation therapy, with two schedules based on Eastern Cooperative Oncology Group
      performance status. The standard treatment was 30 Gy in 10 fractions over 2
      weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5
      fractions over a one week period. Clinical evaluation was performed at 2 weeks
      and 6 months. RESULTS: At 2 weeks, 69% of patients were hematuria-free. Subgroup
      analysis showed that 79% of patients undergoing hypofractionated regimen were
      hematuria-free. A total of 54% were hematuria-free with the standard regimen.
      Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle
      invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of
      patients had relapsed, regardless of tumor stage or therapy schedules.
      CONCLUSIONS: Hemostatic radiotherapy is an effective option for palliative-care
      hematuria related to bladder cancer in patients unfit for surgery. Although it
      appears to be rapidly effective, its effect is of limited duration.
      Hypofractionation also seems to be an effective option; however larger cohorts
      and prospective trials are needed to evaluate its efficacy compared to standard
      schedules.

PMID- 24456774
TI  - Penile primary melanoma: analysis of 6 patients treated at Brazilian National
      Cancer Institute in the last eight years.
AB  - PURPOSE: To describe our experience in treating penile melanoma in 06 patients
      followed at our institution. MATERIALS AND METHODS: Between 2004 and 2012 six
      consecutive patients with penile melanoma were treated at our Institution. Stage
      of the disease was classified according to the 2002 AJCC pathologic system.
      Melanoma in situ (TIS) was diagnosed in one patient. One patient was staged as
      T1b, two patients as T2b and two patients as T4b. The clinical and pathological
      findings were evaluated. Immunohistochemical tests were performed for Melan-A,
      HNB-45, S-100 and C-KIT. All histological specimens were examined by the same
      pathologist (ABSS). The patients with Cis, stages T1b and one patient T2b
      underwent only local excision. One patient T2b underwent local excision and
      sentinel lymph node dissection. Two patients with melanoma stage T4b underwent
      partial penile amputation. One of these last patients had palpable inguinal lymph
      nodes at diagnosis and underwent bilateral inguinal lymphadenectomy and received
      systemic chemotherapy (dacarbazine, 30 cycles). RESULTS: Mean follow-up was 36.3
      months. One patient, with stage T2b, died after 12 months due to disease
      recurrence with bilateral inguinal involvement. The patient who underwent
      chemotherapy progressed with lung metastases and died after 14 months of follow
      up. The disease-free survival at five years was 33.3%. CONCLUSION: Penile
      melanoma is a disease with poor prognosis in most cases. Local excision or
      partial penile amputation may have effective control for stages T1 and T2
      lesions. Patients who have clinically proven metastases died despite surgical and
      adjuvant chemotherapy.

PMID- 24456775
TI  - Uroflowmetry in a large population of Brazilian men submitted to a health check
      up program and its correlation with IPSS and prostate size.
AB  - PURPOSE: The aim of this study was to assess the uroflowmetry data in a large
      population of asymptomatic Brazilian men submitted to a health check up program
      and their correlation to IPSS and prostate size. MATERIALS AND METHODS:
      Asymptomatic men underwent a health check-up program between January and December
      2012. The inclusion criteria were men between 40 and 70 years, IPSS <= 7, without
      bladder, prostate, urethral surgery, neurological diseases, urinary tract
      infection, PSA < 4.0 ng/dL and urinary volume higher than 150 mL. Urological
      assessment consisted of clinical history, IPSS, digital rectal examination (DRE),
      prostate specific antigen (PSA), urinalysis, ultrasonography and uroflowmetry.
      RESULTS: A total of 1041 asymptomatic men were included in this study. The
      average age was 49 years and average maximum flow rate was 17.4 mL/s. In spite of
      IPSS and prostate size increase with aging, they had a weak correlation with Qmax
      cutoffs (10 mL/s and 15 mL/s). A total of 85 men (8.3%) had more than 60 years,
      and even in this group, Qmax was higher than 15 mL/s. Out of 1041 men, 117 had
      IPSS less than 8 and Qmax less than 10 mL/s. CONCLUSIONS: In asymptomatic men
      there is a weak correlation between IPSS, prostate size and uroflowmetric data.
      The establishment of different normal cutoffs seems to be complicated and
      uroflowmetry data should be interpreted with caution in order to avoid
      misdiagnosis.

PMID- 24456776
TI  - Pelvic floor muscle strength evaluation in different body positions in
      nulliparous healthy women and its correlation with sexual activity.
AB  - OBJECTIVE: The aim of this study was to assess pelvic floor muscle (PFM) strength
      in different body positions in nulliparous healthy women and its correlation with
      sexual activity. MATERIALS AND METHODS: Fifty healthy nulliparous women with mean
      age of 23 years were prospectively studied. Subjective evaluation of PFM was
      assessed by transvaginal digital palpation (TDP) of anterior and posterior areas
      regarding the vaginal introitus. A perineometer with inflatable vaginal probe was
      used to assess the PFM strength in four different positions: supine with extended
      lower limbs (P1); bent-knee supine (P2); sitting (P3); standing (P4). RESULTS:
      Physical activity, 3 times per week, was reported by 58% of volunteers. Sexual
      activity was observed in 80% of women and 82% of them presented orgasm. The
      average body mass index (BMI) was 21.76 kg/m2, considered as normal according
      World Health Organization (WHO). We observed that 68% of volunteers were
      conscious about the PFM contraction. TDP showed concordance of 76% when anterior
      and posterior areas were compared (p = 0.00014). There was not correlation
      between PFM strength and orgasm in subjective evaluation. The PFM strength was
      significantly higher in standing position when compared with the other positions
      (p < 0.000). No statistical difference was observed between orgasm and PFM
      strength when objective evaluations were performed. CONCLUSIONS: There was
      concordance between anterior and posterior areas in 76% of cases when subjective
      PFM strength was assessed. In objective evaluation, higher PFM strength was
      observed when volunteers were standing. No statistical correlation was observed
      between PFM strength and orgasm in nulliparous healthy women.

PMID- 24456777
TI  - Study of the ureter structure in anencephalic fetuses.
AB  - PURPOSE: The objective of this paper is to analyze the structure of the ureter in
      normal and anencephalic human fetuses. MATERIALS AND METHODS: We studied 16
      ureters from 8 human fetuses without congenital anomalies aged 16 to 27 weeks
      post-conception (WPC) and 14 ureters from 7 anencephalic fetuses aged 19 to 33
      WPC. The ureters were dissected and embedded in paraffin, from which 5 MUm thick
      sections were obtained and stained with Masson trichrome, to quantify smooth
      muscle cells (SMC) and to determine the ureteral lumen area, thickness and
      ureteral diameter. The samples were also stained with Weigert Resorcin Fucsin (to
      study elastic fibers) and Picro-Sirius Red with polarization and
      immunohistochemistry analysis of the collagen type III fibers to study collagen.
      Stereological analysis of collagen, elastic system fibers and SMC were performed
      on the sections. Data were expressed as volumetric density (Vv-%). The images
      were captured with an Olympus BX51 microscope and Olympus DP70 camera. The
      stereological analysis was done using the Image Pro and Image J programs. For
      biochemical analysis, samples were fixed in acetone, and collagen concentrations
      were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were
      statistically compared using the unpaired t-test (p < 0.05). RESULTS: The
      ureteral epithelium was well preserved in the anencephalic and control groups. We
      did not observe differences in the transitional epithelium in the anencephalic
      and control groups. There was no difference in elastic fibers and total collagen
      distribution in normal and anencephalic fetuses. SMC concentration did not differ
      significantly (p = 0.1215) in the anencephalic and control group. The ureteral
      lumen area (p = 0.0047), diameter (p = 0.0024) and thickness (p = 0.0144) were
      significantly smaller in anencephalic fetuses. CONCLUSIONS: Fetuses with
      anencephaly showed smaller diameter, area and thickness. These differences could
      indicate that anencephalic fetal ureters tend to have significant structural
      alterations, probably due to cerebral lesions with consequent brain control
      damage of ureter nerves.

PMID- 24456778
TI  - Association between urinary symptoms and quality of life in HTLV-1 infected
      subjects without myelopathy.
AB  - OBJECTIVE: To investigate the relationship between urinary symptoms and quality
      of life of patients infected with HTLV-1. MATERIALS AND METHODS: This is a cross
      sectional study that enrolled individuals with HTLV-1 positive serology from
      February 2010 to March 2011. Participants were HTLV-1 infected subjects followed
      in the HTLV-1 clinic of the University Hospital in Salvador, Bahia, Brazil.
      Patients with HTLV-1 associated myelopathy / tropical spastic paraparesis
      (HAM/TSP), who had evidence of other neurological diseases, diabetes mellitus or
      were pregnant were excluded from the study. The questionnaire SF-36 was used to
      evaluate quality of life and the questionnaire OAB-V8 was used to evaluate
      urinary symptoms. RESULTS: From the 118 individuals evaluated, 50 (42.4%)
      complained of urinary symptoms and 68 (57.6%) did not. Most participants were
      females. There was no difference between the groups regarding demographic
      variables. The group with symptoms showed significantly lower scores in all
      domains of the SF-36 questionnaire. The domains with greatest differences were
      vitality and general health state. CONCLUSIONS: Urinary symptoms negatively
      influence the quality of life of individuals infected with HTLV-1.

PMID- 24456779
TI  - Urinary symptoms and urodynamics findings in patients with Friedreich's ataxia.
AB  - PURPOSE: To assess the prevalence of LUTS, urinary tract and urodynamics changes
      in patients with Friedreich's Ataxia (FA), the most common form of hereditary
      ataxia. MATERIALS AND METHODS: This study evaluated 258 patients with genetically
      confirmed diagnoses of FA. Of the patients, 158 responded to a questionnaire
      which assessed their urinary symptoms. Patients with clinical changes underwent
      renal function examinations, ultrasound, and urodynamic studies (UDS). RESULTS:
      The sample analyzed showed that 82% of the patients complained of LUTS, although
      only 22% related the symptoms with quality of life impairment. Twenty eight (18%)
      of them agreed to undergo urodynamic evaluation. Urgency was the most common
      symptom. The exam was normal in 4 (14%) and detrusor underactivity was the most
      common finding. 14% (4 patients) presented with dilatation of the upper urinary
      tract at ultrasound scans. None of them had creatinine alterations. CONCLUSIONS:
      LUTS was found in a large percentage of patients with FA, but only a few related
      it to their quality of life impairment. Although creatinine levels was normal in
      this sample, some patients may show upper urinary tract abnormalities, with
      deserves close observation and proper care.

PMID- 24456780
TI  - Five-alpha reductase inhibitor influences expression of androgen receptor and
      HOXB13 in human hyperplastic prostate tissue.
AB  - OBJECTIVES: Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive
      agents in prostate cancer with a risk of high-grade disease. This study evaluated
      the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate
      cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate
      cancer cells. MATERIALS AND METHODS: We retrospectively selected 21 patients who
      underwent TURP between March 2007 and February 2010 for previously confirmed BPH
      by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI
      treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate
      tissue was evaluated by immunohistochemical staining. We tested the effect of
      5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP
      cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation
      assay, and ELISA. RESULTS: Group 2 showed stronger reactivity for AR and HOXB13
      than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI.
      At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA
      in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR
      expression but it stimulated the expression of HOXB13. CONCLUSIONS: These results
      demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells
      and human prostate tissue. In order to use 5ARI in chemoprevention of prostate
      cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic
      proteins and its regulation pathway.

PMID- 24456781
TI  - Keratinized versus non-keratinized preputial flap onlay urethroplasty: does it
      make any difference in the histological analysis? An experimental study in
      rabbits.
AB  - PURPOSE: To compare the histological characteristics of keratinized versus non
      keratinized onlay island flaps in an experimental rabbit model. MATERIALS AND
      METHODS: Sixteen male rabbits were randomly allocated into two experimental
      groups: keratinized and non-keratinized onlay island flaps. A defect was created
      in the ventral aspect of the penile urethra. In the keratinized group, a
      longitudinal island flap was harvested from the external prepuce and rotated to
      cover the urethral defect. In the non-keratinized group a transverse island flap
      was harvested from the inner prepuce. The animals were sacrificed after 2, 4, 8
      and 12 weeks. RESULTS: The flaps were viable in all animals, and no deaths were
      associated with the procedure. Two urethrocutaneous fistulas were identified, one
      in each experimental group. A similar pattern of fibrosis was identified in both
      groups. The keratinized epithelium of the external prepuce kept its histological
      aspect and keratin production. Both keratinized and non-keratinized groups
      presented a slight decrease on the epithelial thickness, however without a
      statistically significant difference between groups. CONCLUSIONS: In this short
      term rabbit model, we observed that the stratified squamous keratinized
      epithelium from the external prepuce kept its keratin production. There was no
      statistical influence of the flap type on the mean epithelial thickness.

PMID- 24456782
TI  - Expanded criteria for video endoscopic inguinal lymphadenectomy (VEIL) in penile
      cancer: palpable lymph nodes.
AB  - INTRODUCTION: Open inguinal lymphadenectomy is the gold standard for the
      treatment of inguinal metastasis in patients with penile cancer (PC). Recently
      the Video Endoscopic Inguinal Lymphadenectomy (VEIL) was proposed as an option to
      reduce the morbidity of the procedure in patients without palpable inguinal lymph
      nodes (PILN), however the oncological equivalency in patients with PILN remains
      poorly studied. The aims of this video are the demonstration of VEIL in patients
      with PILN and present the preliminary experience comparing patients with and
      without PILN. MATERIALS AND METHODS: The video illustrates the procedure
      performed in two cases that were previously underwent partial penectomy for PC
      with PILN. Data from the series of 15 patients (22 limbs operated) with PILN
      underwent VEIL were compared with our series of VEIL in 25 clinically N0 patients
      (35 limbs operated). RESULTS: The comparison between the groups with and without
      PILN found, respectively, these outcomes: age 52,45 x 53,2 years, operative time
      126,8 x 95,5 minutes, hospital stay 5. x 3.1 days, drainage time 6.7 x 5.7 days,
      9 resected lymph nodes on average in both groups, global complications 32% x 26%,
      cellulitis 4.5% x 0%, lymphocele 23% in both groups, skin necrosis 0% x 3%,
      myocutaneous necrosis 4.5% x 0%, pN+ 33% x 32 %, cancer specific mortality 7 % x
      5 % and mean follow-up 17.3 x 35.3 months. None of the variables presented p <
      0.05. CONCLUSIONS: VEIL is a safe complementary procedure for treatment of PC,
      even in patients with PILN. Oncological results in patients with PILN seem to be
      appropriate but are still very premature. Prospective multicenter studies with
      larger samples and long-term follow-up should be conducted to determine the
      oncological equivalence of VEIL compared with open surgery in patients with PILN.

PMID- 24456783
TI  - Laparoendoscopic single-site nephroureterectomy for morbid obese patients.
AB  - Since the first laparoendoscopic single-site (LESS) surgery report in urology in
      2007 (1) (Rane A e Cadeddu JA), the few reports of LESS extraperitoneal access in
      the literature were mainly described for less complex cases. The aim of this
      video is to demonstrate the feasibility of LESS extraperitoneal access in a
      morbid obese patient presenting a malignant tumor in the renal pelvis. The
      patient is positioned in 90-degree lateral decubitus. An incision is made below
      the abdominal skin crease on the left side of the patient and the anterior rectus
      fascia is vertically incised with manual dissection of the extra/retroperitoneal
      space. We use an Alexis(r) retractor to retract the skin maximizing the incision
      orifice. Three trocars (12, 10 and 5 mm) are inserted through a sigle-port. The
      pedicle was controlled "en bloc" with a vascular stapler and the bladder cuff
      treated by the conventional open approach through the same incision. Operative
      time was 126 minutes with minimal blood loss. The pathology reported high grade
      papillary urothelial carcinoma in the pelvis (pT3N0M0) and in the ureter (pTa).
      LESS extraperitoneal nephroureterectomy is feasible and safe, even in more
      complex cases. It is a good alternative for morbid obese patients and for
      patients with synchronous distal ureteral tumors for whom an open approach to the
      bladder cuff is proposed to avoid incisions in two compartments of the abdominal
      wall. 

PMID- 24456784
TI  - Cloacal exstrophy: a complex disease.
AB  - INTRODUCTION: Cloacal exstrophy is a rare occurrence with an incidence of
      1:200,000 to 1:400,000 live births. It represents one of the most challenging
      reconstructive endeavors faced by pediatric surgeons and urologists. Aside from
      the genitourinary defects, there are other associated anomalies of the
      gastrointestinal, musculoskeletal and neurological systems that require a
      multidisciplinary approach when counseling anxious parents. MATERIAL AND METHODS:
      We present a video of a patient with cloacal exstrophy treated with 21 days of
      life. Surgery consisted of separation and tubularization of the cecal plate from
      the exstrophied bladder halves and colostomy construction. The bladder was closed
      primarily and umbilical scar reconstructed and used for ureteral and cistostomy
      drainage. A urethral catheter was used to guide bladder neck tubularization. A
      final epispadic penis was obtained and planned for further repair in a second
      step. RESULTS: The patient had an initial uneventful postoperative course and
      immediate outcome was excellent. The bladder healed nicely but patient presented
      with abdominal distension in the 5th day of postoperative setting requiring
      parenteral nutrition. The distal colon persisted with lower diameter although non
      obstructive, but causing difficulty for fecal progression. Continuous colostomy
      dilatation and irrigation were required. CONCLUSIONS: Approximating the bladder
      halves in the midline at birth and primary bladder closure is a viable option,
      intestinal transit may be a issue of concern in the early postoperative follow
      up.

PMID- 24456785
TI  - Systematic review and meta-analysis of target terapies for the treatment of
      metastatic renal cancer.
AB  - OBJECTIVES: At present there are several drugs for the treatment of advanced
      renal cell carcinoma (ARCC). The main objective of this work was to perform a
      systematic review (SR) and meta-analysis (MA) of clinical randomized studies that
      compared target cell therapies (TCT). MATERIALS AND METHODS: SR identified
      clinical randomized trials that compared TCT versus interferon-alpha in the
      treatment of patients with ARCC. In order to analyze efficiency, it was evaluated
      free-survival progression (FSP), total survival (TS) and response rate (RR).
      RESULTS: In relation to first line treatment, seven studies of TCT were
      identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two
      studies with sorafenib and everolimus for second line treatment. Relative risk
      (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94%
      and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38,
      sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus,
      0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line
      treatment of all analyzed drugs. As for RR significant results were: sunitinib,
      3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI =
      1.43-2.71. CONCLUSIONS: For first line treatment, sunitinib was the most
      effective TCT in relation to FPS; there was no alteration of TS and RR was small
      but significant for sunitinib and bevacizumab. Available studies could not
      conclude any results for second line treatments.

PMID- 24456786
TI  - Delayed ureterectomy after incomplete nephroureterectomy for upper tract
      urothelial carcinoma: pathologic findings and outcomes.
AB  - OBJECTIVES: To evaluate the pathologic findings and outcomes after distal
      ureterectomy for a retained ureteral segment following incomplete
      nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter.
      MATERIALS AND METHODS: After IRB approval, an institutional database identified
      patients who underwent distal ureterectomy for a retained ureteral segment after
      assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter
      or renal pelvis. Clinical and pathologic variables were analyzed. RESULTS: From
      January 1993 to July 2007, 12 patients were identified with median age at the
      time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was
      open in 9 patients and laparoscopic in 3 patients. The median time from
      nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the
      time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4
      patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6
      patients and grade 3 in six patients. Pathology from the subsequent surgery
      demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients,
      dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local
      recurrence in 2 patients was present in a segment of ureter discontinuous with
      the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with
      initial grade 3 renal pelvis lesions, developed metastatic disease. CONCLUSIONS:
      Tumor recurrence in a retained ureteral segment after incomplete
      nephroureterectomy is a significant problem and may contribute to intravesical
      recurrence or metastatic disease. Complete, en bloc resection is imperative to
      minimize these risks.

PMID- 24456787
TI  - Effects of terazosin and tolterodine on ureteral stent related symptoms: a double
      blind placebo-controlled randomized clinical trial.
AB  - OBJECTIVE: To evaluate the effects of terazosin and tolterodine on ureteral stent
      discomfort. MATERIALS AND METHODS: Of 163 patients assessed for eligibility, 104
      patients were randomly assigned to receive placebo, 2 mg of terazosin twice
      daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the
      stenting period. Prior to stenting and at stent removal, the International
      Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the
      Visual Analog Scale for Pain were determined. The patients also reported their
      analgesic use during the stenting period. RESULTS: Ninety-four patients completed
      the study. We noted significant decreases in the total IPSS scores (p = 0.002),
      irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding
      pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However,
      neither the obstructive subscore nor the suprapubic pain improved significantly
      (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus
      tolterodine experienced significant reductions in the total IPSS, irritative
      symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared
      with those patients receiving placebo. However, compared with placebo, terazosin
      monotherapy did not affect pain levels, and tolterodine monotherapy did not
      improve QoL, flank pain or analgesics use. CONCLUSIONS: Terazosin plus
      tolterodine improves ureteral stent-related complications, including irritative
      symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but
      does not decrease obstructive symptoms or suprapubic pain. This trial was
      registered at www.clinicaltrials.gov as NCT01530243.

PMID- 24456788
TI  - Use of screws and cement in primary TKA with up to 20 years follow-up.
AB  - The purpose of this study was to investigate screws and cement for large tibial
      bone defects during primary TKA. Of 14,686 consecutive primary TKAs performed
      between December 1988 and February 2010, 256 received screws and cement for
      tibial defects. Cox regression was used for the analysis. 20-year survival
      probability was 0.9897 (screws) and 0.9339 (no screws) (P = .4225 log-rank).
      Tibial bone condition was significantly worse in knees receiving screws (P <
      .0001) with 73.0% having defects in the screws group and 3.4% (P < .0001) for non
      screws. Radiolucency appeared in 13.7% (screws) and 6.4% (no screws)
      postoperatively. Screws were $137 each, wedges $910 to $2240. Knees with tibial
      defects and screws performed similarly if not better than knees without defects
      at substantially lower cost than alternatives.

PMID- 24456789
TI  - Variants in the 5'-upstream region of GPC5 confer risk of lung cancer in never
      smokers.
AB  - BACKGROUND: A recent genome-wide study (GWAS) has identified GPC5 as a promising
      susceptibility gene for Lung cancer in never smokers (LCINS). However, the most
      significant single nucleotide polymorphism (SNP) in this GWAS, rs2352028, has
      yielded controversial results. The aim of this study was to clarify the
      relationship between rs2352028 and LCINS. Considering that rs2352028 might be
      largely marker-SNP correlated to causative variants, two predicted functional
      SNPs, rs3759452 and rs7322083, were additionally investigated in this study.
      METHODS: A hospital based case-control study including 298 cases and 599 controls
      in a never-smoking Chinese Han population was conducted, and then a meta-analysis
      combining our data and published data was performed to verify the findings.
      RESULTS: The SNP rs3759452, predicted to potentially change transcription factor
      binding site of GPC5, was significantly associated with LCINS risk (odds ratio
      for dominant model=1.55, 95% confidence interval=1.14-2.12). Nevertheless, no
      significant evidence was showed for rs2352028, both in our case-control study and
      the meta-analysis including 13 studies of 2342 LCINS cases and 13,398 never
      smoking controls. Further subgroup meta-analysis according to population
      ethnicity and cancer histology also reported no significant association of
      rs2352028. CONCLUSIONS: The association conferring rs3759452 further supports the
      value of GPC5 in susceptibility to LCINS. Nevertheless, comprehensive analyses
      are warranted to dissect the functional mechanism underpinning rs3759452.

PMID- 24456792
TI  - Lack of difference in T wave variability between patients at risk of sudden
      cardiac death and healthy subjects.
AB  - BACKGROUND: T wave variability (Tvar) is a proposed method to predict sudden
      cardiac death (SCD). The purpose of this trial was to evaluate the
      reproducibility of Tvar measurements over time and demonstrate a difference in
      Tvar between patient populations at risk for ventricular arrhythmias and healthy
      subjects. METHODS: Sixty subjects were enrolled in into 3 groups: healthy
      subjects (Population I), patients at high risk of SCD (Population II), and
      patients with a recent ventricular tachyarrhythmia event (Population III).
      Recording and analysis of T wave amplitude variance (TAV) as a measure of Tvar
      was performed at baseline and 3 months. RESULTS: TAV could not be interpreted in
      12 of 43 patients in Populations II and III due to PVCs or noise. No subject had
      a TAV value suggestive of high risk of SCD as per a previously defined cutoff of
      >59 MUV. Median (range) values of TAV in MUV at baseline for Populations I, II
      and III were 26 (15-39), 21 (13-43), and 24 (18-41), respectively (p = 0.39). TAV
      was reproducible within population's from baseline to 3 months (p = 0.27, 0.53,
      0.17 for Populations I, II and III, respectively). There was no significant
      difference between TAV values of high risk patients and healthy subjects.
      CONCLUSION: Tvar was reproducible primarily in patients with left ventricular
      dysfunction. However, the role of Tvar as a risk stratifying tool remains
      inconclusive.

PMID- 24456793
TI  - Development of a novel antimicrobial-releasing glass ionomer cement
      functionalized with chlorhexidine hexametaphosphate nanoparticles.
AB  - BACKGROUND: Glass ionomer cements (GICs) are a class of dental biomaterials. They
      have a wide range of uses including permanent restorations (fillings), cavity
      linings, fissure sealants and adhesives. One of the most common reasons for
      replacing a dental restoration is recurrent bacterial tooth decay around the
      margins of the biomaterial. Therefore, a dental biomaterial which creates a
      sustained antimicrobial environment around the restoration would be of
      considerable clinical benefit. In this manuscript, the formulation of a GIC
      containing novel antimicrobial nanoparticles composed of chlorhexidine
      hexametaphosphate at 1, 2, 5, 10 and 20% powder substitution by mass is reported.
      The aim is to create GICs which contain chlorhexidine-hexametaphosphate
      nanoparticles and characterize the nanoparticle size, morphology and charge and
      the release of chlorhexidine and fluoride, tensile strength and morphology of the
      GICs. RESULTS: The GICs released chlorhexidine, which is a broad spectrum
      antimicrobial agent effective against a wide range of oral bacteria, over the
      duration of the experiment in a dose-dependent manner. This was not at the
      expense of other properties; fluoride release was not significantly affected by
      the substitution of antimicrobial nanoparticles in most formulations and internal
      structure appeared unaffected up to and including 10% substitution. Diametral
      tensile strength decreased numerically with substitutions of 10 and 20%
      nanoparticles but this difference was not statistically significant. CONCLUSION:
      A series of GICs functionalized with chlorhexidine-hexametaphosphate
      nanoparticles were created for the first time. These released chlorhexidine in a
      dose-dependent manner. These materials may find application in the development of
      a new generation of antimicrobial dental nanomaterials.

PMID- 24456795
TI  - miR-150 promotes the proliferation and migration of lung cancer cells by
      targeting SRC kinase signalling inhibitor 1.
AB  - microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs
      that play an important role in the regulation of gene expression at the post
      transcriptional level. Dysregulation of miRNAs is associated with a variety of
      diseases, including lung cancer. In the present study, miR-150 was found to be
      significantly upregulated in lung cancer clinical specimens by quantitative real
      time polymerase chain reaction (RT-PCR). Using bioinformatics analysis, v-src
      avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) kinase signalling
      inhibitor 1 (SRCIN1), an important regulator of SRC activity, was predicted to be
      a potential target of miR-150. Furthermore, an inverse correlation between miR
      150 and SRCIN1 protein levels, but not mRNA levels, was identified in human lung
      cancer tissue samples. By overexpressing or knocking down miR-150 in lung
      adenocarcinoma A549 cells and H1975 cells, it was experimentally validated that
      miR-150 is a direct regulator of SRCIN1. It was further confirmed that miR-150
      directly recognises the 3'-untranslated region (3'-UTR) of SRCIN1 transcript with
      a luciferase reporter assay. Finally, it was demonstrated that the repression of
      SRCIN1 by miR-150 consequently triggered the activation of the Src/focal adhesion
      kinase (FAK) and Src/Ras/extracellular signal-regulated kinase (ERK) pathway,
      which eventually promoted the proliferation and migration of A549 cells, and this
      promotion by miR-150 could be reversed by overexpressing SRCIN1. Taken together,
      our findings provide the first clues regarding the role of miR-150 as an oncogene
      in lung cancer through the inhibition of SRCIN1 translation. 

PMID- 24456796
TI  - Papillomaviruses in felids.
AB  - The ability of papillomaviruses (PVs) to cause disease in human beings and most
      domestic animals has long been recognised. However, disease due to PVs in cats
      was not reported until 1990. Since this first description of feline cutaneous
      viral plaques, additional feline diseases have been causally linked to PVs, and
      PV-induced disease has been reported in a wide range of felids. In this review,
      the PV replication cycle and the subsequent immune response are discussed, along
      with diagnostic methods to confirm intralesional infection. In domestic cats,
      viral plaques, Bowenoid in situ carcinomas and feline sarcoids are thought to be
      caused by PV infection; the appearance, clinical behaviour and causative PVs of
      these diseases are discussed. Recent evidence that PVs could also be a
      significant cause of feline cutaneous squamous cell carcinomas is reviewed.
      Lastly, PV-associated diseases of exotic felids are presented. 

PMID- 24456794
TI  - A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with
      erlotinib or everolimus in patients with solid tumours.
AB  - BACKGROUND: LY2584702 tosylate (hereafter referred to as LY2584702) is an oral,
      selective ATP competitive inhibitor of p70 S6 kinase. Preclinical studies with
      LY2584702 demonstrated significant synergistic activity with erlotinib and
      everolimus. The primary objective was to determine a phase II dose and schedule.
      Secondary objectives included evaluation of safety, toxicity and pharmacokinetics
      of LY2584702 in combination with erlotinib or everolimus. METHODS: Patients with
      advanced solid tumours were treated with a total daily dose of 50-200mg of
      LY2584702 in combination with erlotinib 150 mg once daily (Arm A) or everolimus
      10mg once daily (Arm B). Dose escalation was based on 3+3 design and used the
      Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: Twenty-nine
      patients were enrolled, 17 in Arm A and 12 in Arm B. Dose limiting toxicities
      (DLTs) in cycle 1 were observed in Arm A in four patients and consisted of Grade
      3 vomiting, hypophosphataemia, pulmonary embolism and decreased clotting factor
      V. No DLTs were observed in Arm B at cycle 1, and the most frequent treatment
      emergent adverse events related to study drug were: fatigue, anorexia, diarrhoea,
      nausea and vomiting. Seven patients received >=4 cycles (3 in A, 4 in B). Best
      overall response was stable disease. Exposure accumulation of LY2584702 occurred
      with BID (twice daily) dosing. Exposure of erlotinib increased when administered
      in combination with LY2584702. CONCLUSION: LY2584702 was not well tolerated when
      administered with erlotinib, therefore this combination is not feasible. The
      combination with everolimus was better tolerated but yielded very limited
      clinical benefit.

PMID- 24456797
TI  - Evaluation of different enzyme-linked immunosorbent assays for the diagnosis of
      brucellosis due to Brucella melitensis in sheep.
AB  - Six serological assays for the diagnosis of ovine brucellosis, due to Brucella
      melitensis were evaluated. Reference serum samples from sheep of known B.
      melitensis infection status (n=118) were assessed using the Rose Bengal test
      (RBT), complement fixation test (CFT) and four commercial enzyme-linked
      immunosorbent assays (ELISAs), including two indirect ELISAs (iELISAs), one
      competitive ELISA (cELISA) and one blocking ELISA (bELISA). The highest
      differential positive rates (DPR) were obtained with the cELISA and bELISA, while
      the lowest DPR was estimated using iELISAs. A latent class analysis was performed
      to estimate the accuracy of the CFT, RBT and bELISA using 1827 sera from sheep
      undergoing testing as part of a surveillance and control programme. Lower
      sensitivity and specificity were obtained for the three serological tests when
      the field samples were used. A higher DPR was achieved by the CFT, compared to
      bELISA and RBT. The results suggest that ELISAs, and particularly the bELISA,
      might be suitable for inclusion in the European Union legislation on intra
      community trade for diagnosing B. melitensis infection in sheep, as it has a
      similar test performance compared to the RBT. 

PMID- 24456800
TI  - Pattern formation and mass transfer under stationary solutal Marangoni
      instability.
AB  - According to the seminal theory by Sternling and Scriven, solutal Marangoni
      convection during mass transfer of surface-active solutes may occur as either
      oscillatory or stationary instability. With strong support of Manuel G. Velarde,
      a combined initiative of experimental works, in particular to mention those of
      Linde, Wierschem and coworkers, and theory has enabled a classification of
      dominant wave types of the oscillatory mode and their interactions. In this way a
      rather comprehensive understanding of the nonlinear evolution of the oscillatory
      instability could be achieved. A comparably advanced state-of-the-art with
      respect to the stationary counterpart seemed to be out of reach a short time ago.
      Recent developments on both the numerical and experimental side, in combination
      with assessing an extensive number of older experiments, now allow one to draw a
      more unified picture. By reviewing these works, we show that three main building
      blocks exist during the nonlinear evolution: roll cells, relaxation oscillations
      and relaxation oscillations waves. What is frequently called interfacial
      turbulence results from the interaction between these partly coexisting basic
      patterns which may additionally occur in different hierarchy levels. The second
      focus of this review lies on the practical importance of such convection patterns
      concerning their influence on mass transfer characteristics. Particular attention
      is paid here to the interaction between Marangoni and buoyancy effects which
      frequently complicates the pattern formation even more. To shed more light on
      these dependencies, new simulations regarding the limiting case of stabilizing
      density stratification and vanishing buoyancy are incorporated.

PMID- 24456799
TI  - Transplantation of umbilical cord-derived mesenchymal stem cells into the striata
      of R6/2 mice: behavioral and neuropathological analysis.
AB  - INTRODUCTION: Huntington's disease (HD) is an autosomal dominant disorder caused
      by an expanded CAG repeat on the short arm of chromosome 4 resulting in cognitive
      decline, motor dysfunction, and death, typically occurring 15 to 20 years after
      the onset of motor symptoms. Neuropathologically, HD is characterized by a
      specific loss of medium spiny neurons in the caudate and the putamen, as well as
      subsequent neuronal loss in the cerebral cortex. The transgenic R6/2 mouse model
      of HD carries the N-terminal fragment of the human HD gene (145 to 155 repeats)
      and rapidly develops some of the behavioral characteristics that are analogous to
      the human form of the disease. Mesenchymal stem cells (MSCs) have shown the
      ability to slow the onset of behavioral and neuropathological deficits following
      intrastriatal transplantation in rodent models of HD. Use of MSCs derived from
      umbilical cord (UC) offers an attractive strategy for transplantation as these
      cells are isolated from a noncontroversial and inexhaustible source and can be
      harvested at a low cost. Because UC MSCs represent an intermediate link between
      adult and embryonic tissue, they may hold more pluripotent properties than adult
      stem cells derived from other sources. METHODS: Mesenchymal stem cells, isolated
      from the UC of day 15 gestation pups, were transplanted intrastriatally into 5
      week-old R6/2 mice at either a low-passage (3 to 8) or high-passage (40 to 50).
      Mice were tested behaviorally for 6 weeks using the rotarod task, the Morris
      water maze, and the limb-clasping response. Following behavioral testing, tissue
      sections were analyzed for UC MSC survival, the immune response to the
      transplanted cells, and neuropathological changes. RESULTS: Following
      transplantation of UC MSCs, R6/2 mice did not display a reduction in motor
      deficits but there appeared to be transient sparing in a spatial memory task when
      compared to untreated R6/2 mice. However, R6/2 mice receiving either low- or high
      passage UC MSCs displayed significantly less neuropathological deficits, relative
      to untreated R6/2 mice. CONCLUSIONS: The results from this study demonstrate that
      UC MSCs hold promise for reducing the neuropathological deficits observed in the
      R6/2 rodent model of HD.

PMID- 24456801
TI  - Sorption on eggshell waste--a review on ultrastructure, biomineralization and
      other applications.
AB  - The structure, adsorption behavior and applications of eggshell waste materials
      have been reviewed. The ultrastructure of eggshell particles has been discussed
      to understand the pore structure as well as the surface geometry of the materials
      leading to its multifarious applicability. Besides, the ultrastructure studies
      give full information regarding the chemical constituents of egghell particles as
      well as eggshell membranes. The process of biomineralization in living organisms,
      their consequent effect of controlling the formation of inorganic-organic
      composites propelling their application in biomimetic designing of advanced
      composites with optimized novel properties leading to advances in materials
      design have been discussed. Utilization of eggshell waste materials for the
      removal of organic dyes and heavy inorganic ions has been reviewed with suitable
      models for understanding their adsorption quality and capacity. The applications
      of these materials in various fields of research have been extensively discussed.

PMID- 24456802
TI  - Microbial synthesis of gold nanoparticles: current status and future prospects.
AB  - Gold nanoparticles have been employed in biomedicine since the last decade
      because of their unique optical, electrical and photothermal properties. Present
      review discusses the microbial synthesis, properties and biomedical applications
      of gold nanoparticles. Different microbial synthesis strategies used so far for
      obtaining better yield and stability have been described. It also includes
      different methods used for the characterization and analysis of gold
      nanoparticles, viz. UV-visible spectroscopy, Fourier transform infrared
      spectroscopy, X ray diffraction spectroscopy, scanning electron microscopy,
      ransmission electron microscopy, atomic force microscopy, electron dispersive X
      ray, X ray photoelectron spectroscopy and cyclic voltametry. The different
      mechanisms involved in microbial synthesis of gold nanoparticles have been
      discussed. The information related to applications of microbially synthesized
      gold nanoparticles and patents on microbial synthesis of gold nanoparticles has
      been summarized. 

PMID- 24456803
TI  - The supposed tumor suppressor gene WWOX is mutated in an early lethal
      microcephaly syndrome with epilepsy, growth retardation and retinal degeneration.
AB  - BACKGROUND: WWOX, encoding WW domain-containing oxidoreductase, spans FRA16D, the
      second most common chromosomal fragile site frequently altered in cancers. It is
      therefore considered a tumor suppressor gene, but its direct implication in
      cancerogenesis remains controversial. METHODS AND RESULTS: By whole-exome
      sequencing, we identified a homozygous WWOX nonsense mutation, p.Arg54*, in a
      girl from a consanguineous family with a severe syndrome of growth retardation,
      microcephaly, epileptic seizures, retinopathy and early death, a phenotype highly
      similar to the abormalities reported in lde/lde rats with a spontaneous
      functional null mutation of Wwox. As in rats, no tumors were observed in the
      patient or heterozygous mutation carriers. CONCLUSIONS: Our finding, a homozygous
      loss-of-function germline mutation in WWOX in a patient with a lethal autosomal
      recessive syndrome, supports an alternative role of WWOX and indicates its
      importance for human viability.

PMID- 24456805
TI  - Adaptation to a simulated central scotoma during visual search training.
AB  - Patients with a central scotoma usually use a preferred retinal locus (PRL)
      consistently in daily activities. The selection process and time course of the
      PRL development are not well understood. We used a gaze-contingent display to
      simulate an isotropic central scotoma in normal subjects while they were
      practicing a difficult visual search task. As compared to foveal search, initial
      exposure to the simulated scotoma resulted in prolonged search reaction time,
      many more fixations and unorganized eye movements during search. By the end of a
      1782-trial training with the simulated scotoma, the search performance improved
      to within 25% of normal foveal search. Accompanying the performance improvement,
      there were also fewer fixations, fewer repeated fixations in the same area of the
      search stimulus and a clear tendency of using one area near the border of the
      scotoma to identify the search target. The results were discussed in relation to
      natural development of PRL in central scotoma patients and potential visual
      training protocols to facilitate PRL development. 

PMID- 24456804
TI  - Adherence of pregnant women to Nordic dietary guidelines in relation to
      postpartum weight retention: results from the Norwegian Mother and Child Cohort
      Study.
AB  - BACKGROUND: Pregnancy is a major life event for women and often connected with
      changes in diet and lifestyle and natural gestational weight gain. However,
      excessive weight gain during pregnancy may lead to postpartum weight retention
      and add to the burden of increasing obesity prevalence. Therefore, it is of
      interest to examine whether adherence to nutrient recommendations or food-based
      guidelines is associated with postpartum weight retention 6 months after birth.
      METHODS: This analysis is based on data from the Norwegian Mother and Child
      Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Diet
      during the first 4-5 months of pregnancy was assessed by a food-frequency
      questionnaire and maternal weight before pregnancy as well as in the postpartum
      period was assessed by questionnaires. Two Healthy Eating Index (HEI) scores were
      applied to measure compliance with either the official Norwegian food-based
      guidelines (HEI-NFG) or the Nordic Nutrition Recommendations (HEI-NNR) during
      pregnancy. The considered outcome, i.e. weight retention 6 months after birth,
      was modelled in two ways: continuously (in kg) and categorically (risk of
      substantial postpartum weight retention, i.e. >= 5% gain to pre-pregnancy
      weight). Associations between the HEI-NFG and HEI-NNR score with postpartum
      weight retention on the continuous scale were estimated by linear regression
      models. Relationships of both HEI scores with the categorical outcome variable
      were evaluated using logistic regression. RESULTS: In the continuous model
      without adjustment for gestational weight gain (GWG), the HEI-NFG score but not
      the HEI-NNR score was inversely related to postpartum weight retention. However,
      after additional adjustment for GWG as potential intermediate the HEI-NFG score
      was marginally inversely and the HEI-NNR score was inversely associated with
      postpartum weight retention. In the categorical model, both HEI scores were
      inversely related with risk of substantial postpartum weight retention,
      independent of adjustment for GWG. CONCLUSIONS: Higher adherence to either the
      official Norwegian food guidelines or possibly also to Nordic Nutrition
      Recommendations during pregnancy appears to be associated with lower postpartum
      weight retention.

PMID- 24456806
TI  - Crowded visual search in children with normal vision and children with visual
      impairment.
AB  - This study investigates the influence of oculomotor control, crowding, and
      attentional factors on visual search in children with normal vision ([NV], n=11),
      children with visual impairment without nystagmus ([VI-nys], n=11), and children
      with VI with accompanying nystagmus ([VI+nys], n=26). Exclusion criteria for
      children with VI were: multiple impairments and visual acuity poorer than 20/400
      or better than 20/50. Three search conditions were presented: a row with
      homogeneous distractors, a matrix with homogeneous distractors, and a matrix with
      heterogeneous distractors. Element spacing was manipulated in 5 steps from 2 to
      32 minutes of arc. Symbols were sized 2 times the threshold acuity to guarantee
      visibility for the VI groups. During simple row and matrix search with
      homogeneous distractors children in the VI+nys group were less accurate than
      children with NV at smaller spacings. Group differences were even more pronounced
      during matrix search with heterogeneous distractors. Search times were longer in
      children with VI compared to children with NV. The more extended impairments
      during serial search reveal greater dependence on oculomotor control during
      serial compared to parallel search.

PMID- 24456807
TI  - Yeast hydrolysate supplementation increases field abundance and persistence of
      sexually mature sterile Queensland fruit fly, Bactrocera tryoni (Froggatt).
AB  - The sterile insect technique (SIT) is a non-chemical approach used to control
      major pests from several insect families, including Tephritidae, and entails the
      mass-release of sterile insects that reduce fertility of wild populations. For
      SIT to succeed, released sterile males must mature and compete with wild males to
      mate with wild females. To reach sexual maturity, the Queensland fruit fly,
      Bactrocera tryoni (Froggatt) (Diptera: Tephritidae), must obtain adequate
      nutrition after adult emergence; however, in current SIT programs sterile B.
      tryoni receive a pre-release diet that lacks key nutrients required to sustain
      sexual development. The chief objective of this study was to determine whether
      pre-release yeast hydrolysate (YH) supplements affect the persistence and
      abundance of sexually mature sterile male B. tryoni under field conditions.
      Experiments were run in outdoor cages under conditions of low and high
      environmental stress that differed markedly in temperature and humidity, and in
      the field. Under low environmental stress conditions, survival of sterile B.
      tryoni was monitored in cages under three diet treatments: (i) sugar only, (ii)
      sugar plus YH or (iii) sugar plus YH for 48 h and sugar only thereafter. Under
      high environmental stress conditions survival of sterile B. tryoni was monitored
      in cages under four diet treatments: (i) white sugar only, (ii) brown sugar only,
      (iii) white sugar plus YH and (iv) brown sugar plus YH. In a replicated field
      study, we released colour-marked sterile B. tryoni from two diet regimes, YH
      supplemented or YH-deprived, and monitored abundance of sexually mature males. In
      the low-stress cage study, there was no effect of diet, although overall females
      lived longer than males. In the high stress cage study, mortality was lower for
      YH-fed flies than YH-deprived flies and females lived longer than males. In the
      field, YH supplementation resulted in higher abundance of sexually mature sterile
      males, with 1.2 YH-fed flies trapped for every YH-deprived fly trapped. Under
      field conditions, YH supplementation can increase over-flooding ratios and hence
      may improve the effectiveness of SIT programmes. 

PMID- 24456808
TI  - Assessment of human hippocampal developmental neuroanatomy by means of ex-vivo 7
      T magnetic resonance imaging.
AB  - During development, the hippocampus undergoes numerous changes in its cell
      morphology and cyto- and myelo-architecture that begin during the fetal period
      and continue after birth. We investigated the developmental changes occurring in
      healthy fetal (20-32 gestational weeks) and post-natal human hippocampi (from 1
      day to adulthood) by combining high-resolution 7 T magnetic resonance imaging
      (MRI) and histological and immunohistochemical analyses in order to compare
      variations in signal intensity with cyto- and myeloarchitectural organization.
      During fetal period the intensity of the T2-weighted images was related to the
      cell density and the subregions of Ammon's horn and dentate gyrus, characterized
      by densely packed neurons, were recognizable as hypointense areas. The inverse
      correlation between MRI signal intensity and cell density was visualized by line
      profile results. At the age of two post-natal weeks, the low MRI signal was still
      related to cell density, although thin myelinated fibers were observed in
      hypointense regions such as the alveus and stratum lacunosum-moleculare. The
      myelin content subsequently increases until the complete hippocampal
      myeloarchitecture is reached in adulthood. Comparison of the MRI findings and
      corresponding histological sections indicated that the differences in the T2
      weighted images between the age of seven years and adulthood reflect the
      increasing density of myelinated fibers. These results provide useful information
      concerning the interpretation of MRI signals and the developmental changes
      visualized by in vivo MRI at lower field strengths, and may be used as a
      reference for the future use of high spatial resolution MRI in clinical practice.

PMID- 24456809
TI  - Influence of chewing time on salivary stress markers.
AB  - PURPOSE: We investigated the influence of chewing time on salivary stress
      markers. METHODS: Participants performed arithmetic calculations for 30min as
      stress loading, followed by chewing for 0, 5, 10, or 15min. All experiments
      finished at 25min after stress loading. With 0-min chewing, saliva was collected
      before stress loading (BS), immediately after stress loading (R0), and at 5, 10,
      15, and 25min after stress loading (R5, 10, 15 and 25). With 5, 10, or 15min
      chewing, saliva was collected at BS and R0, immediately after chewing (Ch5, 10
      and 15, respectively), and 25min after stress loading (Ch5R25, Ch10R25 and
      Ch15R25, respectively). Salivary alpha-amylase activity and cortisol levels were
      measured to evaluate stress. Change in stress markers between R0 and Ch5, 10 and
      15 or R25, Ch5R25, Ch10R25 and Ch15R25 were calculated. RESULTS: No significant
      differences were observed in rate of change in alpha-amylase activity among the
      chewing conditions. Rate of decrease in cortisol levels was significantly greater
      at 15-min chewing than at 5-min chewing. Rate of decrease in cortisol levels was
      significantly greater at 10 and 15-min chewing than at 0-min chewing. CONCLUSION:
      The present results indicate that chewing time affects the reaction of the
      endocrine system to mental stress, and that continuous chewing for more than
      10min is effective in reducing stress.

PMID- 24456810
TI  - Evaluation of a dosing regimen for continuous vancomycin infusion in critically
      ill patients: an observational study in intensive care unit patients.
AB  - PURPOSE: We aimed to evaluate a dosing algorithm for continuous vancomycin
      administration in intensive care unit patients. MATERIALS AND METHODS: This
      observational study was conducted in a medical intensive care unit (German
      university hospital; June 2012-February 2013). Following a loading dose of 20 mg
      per kg actual body weight, vancomycin was administered continuously (20 or 30 mg
      of vancomycin per kg actual body weight over 24 hours depending on renal
      function). The vancomycin infusion rate was adjusted to achieve a target serum
      vancomycin concentration of 20-30 mg/L. RESULTS: Vancomycin was administered for
      a median (interquartile range) of 7 (5-9) days. The median vancomycin dose given
      as an initial bolus was 1750 (1400-2000) mg. The median daily vancomycin dose
      ranged from 480 (180-960) mg (day 6) to 3.120 (2596-3980) mg (day 1). Altogether,
      the achieved median serum vancomycin concentration was 29.0 (25.2-33.2) mg/L. On
      treatment days 1 to 7, we observed target serum vancomycin levels (20-30 mg/L) in
      48%, 39%, 33%, 26%, 43%, 57%, and 69% of patients. Supra-therapeutic serum
      vancomycin concentrations (>30 mg/L) were observed in 36%, 52%, 61%, 63%, 39%,
      19%, and 15% of patients on treatment days 1 to 7. CONCLUSIONS: The evaluated
      vancomycin dosing regimen for continuous infusion allowed rapid achievement of
      sufficient vancomycin serum levels. However, we frequently observed supra
      therapeutic serum vancomycin concentrations in the first days of vancomycin
      treatment.

PMID- 24456811
TI  - Long-term persistence of quality improvements for an intensive care unit
      communication initiative using the VALUE strategy.
AB  - PURPOSE: Communication in the intensive care unit (ICU) is an important component
      of quality ICU care. In this report, we evaluate the long-term effects of a
      quality improvement (QI) initiative, based on the VALUE communication strategy,
      designed to improve communication with family members of critically ill patients.
      MATERIALS AND METHODS: We implemented a multifaceted intervention to improve
      communication in the ICU and measured processes of care. Quality improvement
      components included posted VALUE placards, templated progress note inclusive of
      communication documentation, and a daily rounding checklist prompt. We evaluated
      care for all patients cared for by the intensivists during three separate 3 week
      periods, pre, post, and 3 years following the initial intervention. RESULTS: Care
      delivery was assessed in 38 patients and their families in the pre-intervention
      sample, 27 in the post-intervention period, and 41 in follow-up. Process measures
      of communication showed improvement across the evaluation periods, for example,
      daily updates increased from pre 62% to post 76% to current 84% of opportunities.
      CONCLUSIONS: Our evaluation of this quality improvement project suggests
      persistence and continued improvements in the delivery of measured aspects of ICU
      family communication. Maintenance with point-of-care-tools may account for some
      of the persistence and continued improvements.

PMID- 24456812
TI  - A proteomic approach for the elucidation of the specificity of ectodomain
      shedding.
AB  - Ectodomain shedding (shedding) is a posttranslational modification mechanism,
      which liberates extracellular domains of membrane proteins through juxtamembrane
      processing. Because shedding alters cell characteristics in a rapid and
      irreversible manner, it must be strictly regulated. However, the regulatory
      mechanisms of shedding in response to environmental changes remain obscure. To
      evaluate the regulatory mechanisms of endogenous shedding, we previously
      developed a proteomic screening system to identify shedding targets. This system
      revealed a comprehensive picture of membrane proteins shed under defined
      conditions. In this study, we have improved the screening system to compare the
      shedding patterns in a mouse macrophage cell line treated with two different
      shedding inducers, lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol 13
      acetate (TPA). We show here that LPS simultaneously activates the shedding of
      multiple membrane proteins. We further show that TPA specifically activates the
      shedding of alphaM/beta2 integrin (Mac-1), which was not shed upon LPS
      stimulation of macrophages. These results clearly demonstrate that the regulation
      of endogenous membrane protein shedding is both stimulus- and substrate-specific.
      BIOLOGICAL SIGNIFICANCE: The shedding targets reported to date play pivotal roles
      in a variety of biological phenomena, including the immunological response, cell
      growth, cell adhesion and cell movement. In addition, several disease-related
      membrane proteins are shedding targets. Thus, understanding the regulation of
      shedding is important for the elucidation of pathogenesis and the development of
      therapeutic strategies. We submit that a comprehensive characterization of
      endogenous shedding is indispensable for understanding the regulatory mechanisms
      of shedding, and thus have developed a proteomic screening system to identify
      shedding targets. In this study, using our screening system, we demonstrate that
      different extracellular stimuli activate different types of shedding, even in a
      single cell. Our results prove that this proteomic approach is quite effective
      for the elucidation of the regulatory mechanisms of shedding.

PMID- 24456813
TI  - Elucidation of the unexplored biodiversity of ant venom peptidomes via MALDI-TOF
      mass spectrometry and its application for chemotaxonomy.
AB  - The rise of integrative taxonomy, a multi-criteria approach used in
      characterizing species, fosters the development of new tools facilitating species
      delimitation. Mass spectrometric (MS) analysis of venom peptides from venomous
      animals has previously been demonstrated to be a valid method for identifying
      species. Here we aimed to develop a rapid chemotaxonomic tool for identifying
      ants based on venom peptide mass fingerprinting. The study focused on the
      biodiversity of ponerine ants (Hymenoptera: Formicidae: Ponerinae) in French
      Guiana. Initial experiments optimized the use of automated matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to
      determine variations in the mass profiles of ant venoms using several MALDI
      matrices and additives. Data were then analyzed via a hierarchical cluster
      analysis to classify the venoms of 17 ant species. In addition, phylogenetic
      relationships were assessed and were highly correlated with methods using DNA
      sequencing of the mitochondrial gene cytochrome c oxidase subunit 1. By combining
      a molecular genetics approach with this chemotaxonomic approach, we were able to
      improve the accuracy of the taxonomic findings to reveal cryptic ant species
      within species complexes. This chemotaxonomic tool can therefore contribute to
      more rapid species identification and more accurate taxonomies. BIOLOGICAL
      SIGNIFICANCE: This is the first extensive study concerning the peptide analysis
      of the venom of both Pachycondyla and Odontomachus ants. We studied the venoms of
      17 ant species from French Guiana that permitted us to fine-tune the venom
      analysis of ponerine ants via MALDI-TOF mass spectrometry. We explored the
      peptidomes of crude ant venom and demonstrated that venom peptides can be used in
      the identification of ant species. In addition, the application of this novel
      chemotaxonomic method combined with a parallel genetic approach using COI
      sequencing permitted us to reveal the presence of cryptic ants within both the
      Pachycondyla apicalis and Pachycondyla stigma species complexes. This adds a new
      dimension to the search for means of exploiting the enormous biodiversity of
      venomous ants as a source for novel therapeutic drugs or biopesticides. This
      article is part of a Special Issue entitled: Proteomics of non-model organisms.

PMID- 24456814
TI  - Early infant diagnosis of HIV infection in low-income and middle-income
      countries: does one size fit all?
AB  - Despite expansion of services for prevention of mother-to-child transmission of
      HIV (PMTCT), about 700 infants acquire HIV every day. Early initiation of
      antiretroviral therapy for HIV-infected infants reduces mortality but requires
      diagnosis by virological testing, which is complex, expensive, and inaccessible
      in many settings. Little cost-effectiveness evidence exists about different
      strategies to deliver early infant diagnosis services. Cost-effectiveness will
      vary depending on entry points for testing, underlying prevalences of HIV, PMTCT
      coverage, treatment availability, programme attrition, and other factors.
      Appropriate policy responses are therefore context-specific. In most cases, early
      infant diagnosis should be concentrated at entry points where underlying infant
      HIV prevalence is highest (eg, malnutrition wards). This strategy contrasts with
      the tendency at present to test mainly within PMTCT programmes. If testing is
      undertaken in PMTCT programmes with high coverage, addition of a virological test
      at birth might have advantages, including greater predictive value, earlier
      diagnosis, and better infant follow-up. National programme managers should
      recognise the opportunity costs of the limited resources available, acknowledge
      the changing scenario of PMTCT scale-up, ensure implementation of provider
      initiated testing and counselling, and tailor early infant diagnosis programmes
      to maximise health gains for children. 

PMID- 24456815
TI  - Nitazoxanide inhibits the replication of Japanese encephalitis virus in cultured
      cells and in a mouse model.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) has a significant impact on public
      health. An estimated three billion people in 'at-risk' regions remain
      unvaccinated and the number of unvaccinated individuals in certain Asian
      countries is increasing. Consequently, there is an urgent need for the
      development of novel therapeutic agents against Japanese encephalitis.
      Nitazoxanide (NTZ) is a thiazolide anti-infective licensed for the treatment of
      parasitic gastroenteritis. Recently, NTZ has been demonstrated to have antiviral
      properties. In this study, the anti-JEV activity of NTZ was evaluated in cultured
      cells and in a mouse model. METHODS: JEV-infected cells were treated with NTZ at
      different concentrations. The replication of JEV in the mock- and NTZ-treated
      cells was examined by virus titration. NTZ was administered at different time
      points of JEV infection to determine the stage at which NTZ affected JEV
      replication. Mice were infected with a lethal dose of JEV and intragastrically
      administered with NTZ from 1 day post-infection. The protective effect of NTZ on
      the JEV-infected mice was evaluated. FINDINGS: NTZ significantly inhibited the
      replication of JEV in cultured cells in a dose dependent manner with 50%
      effective concentration value of 0.12 +/- 0.04 MUg/ml, a non-toxic concentration
      in cultured cells (50% cytotoxic concentration = 18.59 +/- 0.31 MUg/ml). The
      chemotherapeutic index calculated was 154.92. The viral yields of the NTZ-treated
      cells were significantly reduced at 12, 24, 36 and 48 h post-infection compared
      with the mock-treated cells. NTZ was found to exert its anti-JEV effect at the
      early-mid stage of viral infection. The anti-JEV effect of NTZ was also
      demonstrated in vivo, where 90% of mice that were treated by daily intragastric
      administration of 100 mg/kg/day of NTZ were protected from a lethal challenge
      dose of JEV. CONCLUSIONS: Both in vitro and in vivo data indicated that NTZ has
      anti-JEV activity, suggesting the potential application of NTZ in the treatment
      of Japanese encephalitis.

PMID- 24456816
TI  - An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the
      parotid gland.
AB  - Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands
      that spreads through direct extension, through the lymphatic vessels, and,
      rarely, hematogenously. When distant metastases have been found, they have been
      reported mainly in the lung. We present an unusual case of carcinoma ex
      pleomorphic adenoma of the parotid gland with splenic metastases. The patient
      presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland
      and he underwent a total parotidectomy with laterocervical lymphadenectomy
      ipsilateral and adjuvant radiation therapy to the right parotid area. One year
      later, the patient showed an ipsilateral supraclavicular lymph node recurrence,
      treated with surgery and radiation therapy. Two more years later, the patient
      developed lung and splenic lesions, detected through CT and PET. He underwent
      splenectomy and pathologic assessment of the specimen showed metastatic carcinoma
      ex pleomorphic adenoma. To our knowledge, there is no reported case of a
      carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated
      for carcinoma ex pleomorphic adenoma should be investigated for distant
      metastases with a long-term follow-up examination for local and distant
      metastases and new splenic lesions in these patients should be investigated. 

PMID- 24456817
TI  - Effect of chronic statin treatment on vascular remodeling determined by
      intravascular ultrasound in patients with acute myocardial infarction.
AB  - Early statin treatment of patients with acute coronary syndrome results in
      vascular changes and improved clinical outcomes. However, the influence of
      chronic statin treatment on the culprit vessel in acute coronary syndrome is not
      fully understood. The aim of this study was to investigate the morphologic
      features of the culprit vessel in acute myocardial infarction by comparing
      patients with and without chronic statin treatment. We enroled consecutive
      patients with AMI, who had hyperlipidemia and primary percutaneous coronary
      intervention guided by intravascular ultrasound within 24 hours of symptom onset.
      Of 155 patients, 73 patients were stratified to the chronic statin group and 82
      to the nonstatin group. Intravascular ultrasound in both the groups showed that
      positive remodeling was significantly less frequent in the chronic statin group
      (46.6%) compared with the nonstatin group (70.7%; p = 0.001). Necrotic core area
      was significantly smaller in the chronic statin group (2.2 +/- 1.3 mm(2))
      compared with the nonstatin group (3.2 +/- 2.1 mm(2); p <0.001). Multivariate
      logistic regression analysis revealed that chronic statin treatment was
      significantly associated with less positive remodeling (odds ratio 0.283, 95%
      confidence interval 0.111 to 0.723, p = 0.008). In conclusion, chronic statin
      treatment reduced positive remodeling in the culprit lesions of patients with
      acute myocardial infarction.

PMID- 24456818
TI  - Acupuncture and moxibustion for stress-related disorders.
AB  - Acupuncture and moxibustion, which medical doctors are licensed by the government
      of Japan to perform, can improve the psychological relationship between doctors
      and patients, especially when it is disturbed by a "game", a dysfunctional
      interpersonal interaction that is repeated unintentionally. This advantage is due
      to the essential properties of acupuncture and moxibustion. Acupuncture and
      moxibustion are helpful in treating somatoform disorders, especially
      musculoskeletal symptoms. In Japan, a holistic acupuncture and moxibustion
      therapy called Sawada-style has been developed. This is based on fundamental
      meridian points that are considered to have effects on central, autonomic
      nervous, immune, metabolic, and endocrine systems to regulate the whole body
      balance. In addition, some of the fundamental points have effects on Qi, blood,
      and water patterns associated with major depression, generalized anxiety
      disorder, eating disorders, and somatoform disorders. The fixed protocol of
      Sawada-style would be suitable for large-scale, randomized, controlled studies in
      the future. Recent systematic reviews indicate that electroacupuncture would be a
      useful addition to antidepressant therapy for some symptoms accompanying
      fibromyalgia. Acupuncture and moxibustion are also recommended for irritable
      bowel syndrome, instead of Western drug therapy. Surprisingly, the dorsal
      prefrontal cerebral cortex, which is associated with a method of scalp
      acupuncture applied for gastrointestinal disorders, has been found to be
      activated in patients with irritable bowel syndrome. It is quite possible that
      regulation of this cortical area is related to the effect of scalp acupuncture.
      This acupuncture method can be effective not only for irritable bowel syndrome
      but also for other stress-related gastrointestinal disorders. 

PMID- 24456819
TI  - Endoscopic surgery as an adjuvant treatment modality before or after definitive
      correction of cloacal anomalies.
AB  - OBJECTIVE: To evaluate the effectiveness of endoscopic surgery before or after
      definitive correction in patients with a persistent cloaca. MATERIALS AND
      METHODS: The medical records of 16 patients diagnosed with persistent urogenital
      sinus at our institution were retrospectively reviewed. Of these 16 patients,
      five underwent endoscopic surgery, such as visual internal urethrotomy or
      transurethral incision by a single surgeon at the time of or after colostomy
      formation or corrective surgery. RESULTS: All patients underwent colostomy 1-2
      days after birth. Three patients were treated by endoscopic procedures before
      corrective surgery owing to voiding difficulty, urinary tract infection, or
      hydrocolpos, at a median age of 1 month. Another two patients underwent
      endoscopic surgery after definitive correction of the cloaca owing to urethral
      stricture or urinary incontinence. After endoscopic surgery, all patients voided
      well without residual urine or were catheterised easily without incontinence.
      Endoscopic modality played a substantial role in managing complications or
      resolving the anatomical barrier to decompress the genitourinary tract in
      patients with a common urogenital sinus length of <3 cm. CONCLUSIONS: Endoscopic
      surgery for a cloacal anomaly is a minimally invasive adjuvant technique for
      bladder neck obstruction, urethral stricture, and hydrocolpos with a thickened
      vaginal septum.

PMID- 24456820
TI  - Comparison of testicular volume differential calculations in adolescents with
      varicoceles.
AB  - PURPOSE: We aimed to develop a conversion formula between different calculations
      for testicular volume asymmetry. MATERIALS AND METHODS: Male adolescents with
      varicoceles who underwent scrotal ultrasound were studied. Two formulas were
      analyzed: (1) testicular volume differential, TVDiff = (RTV - LTV)/(TTV), and (2)
      atrophy index, AI = (RTV - LTV)/(RTV). RTV, LTV, and TTV represent the right,
      left, and total testicular volume. Through transformations and regression a
      conversion formula between the calculations was derived. RESULTS: Based on 248
      ultrasounds, a clear relationship between the two formulas was demonstrated: AI =
      ln[(1.97 * TVDiff) + 1], (p < 0.0001). CONCLUSIONS: Differential testicular
      volumes can easily be converted from one formula to another with near-perfect
      accuracy. The formulas are essentially identical and interchangeable.

PMID- 24456821
TI  - Impulsiveness in chronic hepatitis C patients.
AB  - OBJECTIVE: The objective was to investigate impulsiveness among chronic hepatitis
      C (CHC) patients and its association with sociodemographic, clinical and
      psychopathological factors. METHOD: Ninety-one CHC individuals were enrolled in a
      cross-sectional study at a Brazilian public university-based outpatient's service
      for infectious diseases. They were assessed using the Barrat Impulsiveness Scale,
      Brief Fatigue Inventory, Beck Depression Inventory and Hamilton Anxiety Scale.
      Structured psychiatric interview was performed according to the Mini
      International Neuropsychiatric Interview. Multivariate analysis was performed
      according to linear stepwise forward regression. RESULTS: The total score of
      impulsiveness according to BIS in studied population was 64.6+/-9.8. The scores
      for the nonplanning, cognitive-attentional and motor domains were 23.8+/-5,
      19.4+/-2.9 and 21.4+/-5, respectively. Impulsiveness was associated with lower
      educational level, current interferon-alpha (IFN) use, attention
      deficit/hyperactivity disorder, alcohol use disorder, mixed anxiety and
      depressive disorder, specific phobia, bipolar spectrum disorders and anxiety
      symptoms. During IFN treatment, impulsiveness was also associated with suicide
      risk. CONCLUSION: Impulsiveness was frequent in CHC patients and was associated
      with several psychopathological alterations. Impulsiveness management should be
      considered when attending CHC patients.

PMID- 24456824
TI  - Supplementation with Astragalus polysaccharides alters Aeromonas-induced tissue
      specific cellular immune response.
AB  - Members of the genus Aeromonas inhabit various aquatic environments and are
      responsible for a number of intestinal and extra-intestinal infections in humans
      as well as other animals. Astragalus species are used in Chinese traditional
      medicine as antiperspirant, antihypertensive, diuretic and tonic treatments and
      have been used for treatment of patients with leukemia and uterine cancers. The
      present study was aimed to investigate immunomodulatory effect of Astragalus
      polysaccharides (APS) treatment on Aeromonas hydrophila-infected mice. The
      present data showed that APS-treatment ameliorated neutrophils phagocytic
      activity and reactive oxygen species (ROS) production in intestinal tissues of
      infected mice. Moreover, APS treatment induced a highly significantly (P < 0.001)
      increase in the number of CD4(+) T cells in the intestinal tissues and thymus,
      however, number of CD4(+) T cells in the spleens of infected mice not
      significantly changed with APS treatment. On the other hand, APS-treatment caused
      a very highly significant (P < 0.001) decrease in the number of CD8(+) T cells in
      the spleens and thymus of infected mice. In conclusion, the present data
      suggested that APS treatment reduced ROS production, downmodulated neutrophils
      activity, and increased CD4(+)/CD8(+) T cells ratio in A. hydrophila-infected
      mice. 

PMID- 24456823
TI  - Temsirolimus with or without megestrol acetate and tamoxifen for endometrial
      cancer: a gynecologic oncology group study.
AB  - OBJECTIVES: To determine the response, toxicities, and progression free survival
      of a regimen of temsirolimus with or without hormonal therapy in the treatment of
      advanced, or recurrent endometrial carcinoma. BACKGROUND: Preclinical evidence
      suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to
      hormonal therapy. METHODS: We performed a randomized phase II trial of
      intravenous temsirolimus 25mg weekly versus the combination of weekly
      temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks
      alternating with tamoxifen 20mg bid for three weeks in women with recurrent or
      metastatic endometrial carcinoma. RESULTS: There were 71 eligible patients who
      received at least one dose of therapy with 21 of these treated on the combination
      arm which was closed early because of an excess of venous thrombosis, with 5
      episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three
      responses observed in that arm (14%). A total of 50 eligible patients were
      treated on the single agent arm with 3 episodes of DVT and 11 responses (22%).
      Response rates were similar in patients with prior chemotherapy (7 of 29; 24%)
      and those with no prior chemotherapy (4 of 21; 19%). Two of four patients with
      clear cell carcinoma responded. CONCLUSIONS: Adding the combination of megestrol
      acetate and tamoxifen to temsirolimus therapy did not enhance activity and the
      combination was associated with an excess of venous thrombosis. Temsirolimus
      activity was preserved in patients with prior adjuvant chemotherapy.

PMID- 24456825
TI  - Comparison of various microbial inocula for the efficient anaerobic digestion of
      Laminaria hyperborea.
AB  - BACKGROUND: The hydrolysis of seaweed polysaccharides is the rate limiting step
      in anaerobic digestion (AD) of seaweeds. Seven different microbial inocula and a
      mixture of these (inoculum 8) were therefore compared in triplicate, each grown
      over four weeks in static culture for the ability to degrade Laminaria hyperborea
      seaweed and produce methane through AD. RESULTS: All the inocula could degrade L.
      hyperborea and produce methane to some extent. However, an inoculum of slurry
      from a human sewage anaerobic digester, one of rumen contents from seaweed-eating
      North Ronaldsay sheep and inoculum 8 used most seaweed volatile solids (VS)
      (means ranged between 59 and 68% used), suggesting that these each had efficient
      seaweed polysaccharide digesting bacteria. The human sewage inoculum, an inoculum
      of anaerobic marine mud mixed with rotting seaweed and inoculum 8 all developed
      to give higher volumes of methane (means between 41 and 62.5 ml g-1 of seaweed VS
      by week four) ,compared to other inocula (means between 3.5 and 27.5 ml g-1 VS).
      Inoculum 8 also gave the highest acetate production (6.5 mmol g-1 VS) in a single
      stage fermenter AD system and produced most methane (8.4 mL mmol acetate-1) in
      phase II of a two-stage AD system. CONCLUSIONS: Overall inoculum 8 was found to
      be the most efficient inoculum for AD of seaweed. The study therefore showed that
      selection and inclusion of efficient polysaccharide hydrolysing bacteria and
      methanogenic archaea in an inoculum offer increased methane productivity in AD of
      L. hyperborea. This inoculum will now being tested in larger scale (10L)
      continuously stirred reactors optimised for feed rate and retention time to
      determine maximum methane production under single-stage and two-stage AD systems.

PMID- 24456826
TI  - Four-dimensional digital subtraction angiography: implementation and
      demonstration of feasibility.

PMID- 24456827
TI  - Flow diversion technologies in evolution: a review of the first 4 generations of
      flow diversion devices.

PMID- 24456828
TI  - The current cancer care crisis and considerations for neurosurgery.

PMID- 24456829
TI  - Leukoaraiosis and procedural stroke risk in symptomatic carotid stenosis.

PMID- 24456830
TI  - Replication interference between human papillomavirus types 16 and 18 mediated by
      heterologous E1 helicases.
AB  - BACKGROUND: Co-infection of multiple genotypes of human papillomavirus (HPV) is
      commonly observed among women with abnormal cervical cytology, but how different
      HPVs interact with each other in the same cell is not clearly understood. A
      previous study using cultured keratinocytes revealed that genome replication of
      one HPV type is inhibited by co-existence of the genome of another HPV type,
      suggesting that replication interference occurs between different HPV types when
      co-infected; however, molecular mechanisms underlying inter-type replication
      interference have not been fully explored. METHODS: Replication interference
      between two most prevalent HPV types, HPV16 and HPV18, was examined in HPV
      negative C33A cervical carcinoma cells co-transfected with genomes of HPV16 and
      HPV18 together with expression plasmids for E1/E2 of both types. Levels of
      HPV16/18 genome replication were measured by quantitative real-time PCR. Physical
      interaction between HPV16/18 E1s was assessed by co-immunoprecipitation assays in
      the cell lysates. RESULTS: The replication of HPV16 and HPV18 genomes was
      suppressed by co-expression of E1/E2 of heterologous types. The interference was
      mediated by the heterologous E1, but not E2. The oligomerization domain of HPV16
      E1 was essential for HPV18 replication inhibition, whereas the helicase domain
      was dispensable. HPV16 E1 co-precipitated with HPV18 E1 in the cell lysates, and
      an HPV16 E1 mutant Y379A, which bound to HPV18 E1 less efficiently, failed to
      inhibit HPV18 replication. CONCLUSIONS: Co-infection of a single cell with both
      HPV16 and HPV18 results in replication interference between them, and physical
      interaction between the heterologous E1s is responsible for the interference.
      Heterooligomers composed of HPV16/18 E1s may lack the ability to support HPV
      genome replication.

PMID- 24456832
TI  - Anastomotic leaks: technique and timing of detection.
AB  - BACKGROUND: Despite the proven benefits of laparoscopic colorectal surgery, the
      rate of anastomotic leaks has not changed. This study looks at the time of
      presentation of anastomotic leaks between laparoscopic and open colectomies.
      METHODS: Retrospective chart review was performed between July 2008 and 2012. Two
      groups were created, laparoscopic and open. The time of presentation of
      significant leaks requiring reoperation were compared between the groups by index
      colectomies. Statistical analysis is presented as paired t test and chi-square
      test (P < .05). RESULTS: From 1,424 segmental colectomies, the anastomotic leak
      rate between the two groups was not statically significant (P = .69). No
      difference in the time of leak detection was evident (P = .67). Mortality rate
      was equal between the groups. The overall complication rate of the entire cohort
      was statically significant (P <= .001). CONCLUSION: The timing of anastomotic
      leak detection does not differ between laparoscopy and open colorectal
      resections.

PMID- 24456831
TI  - A life-course approach to healthy ageing: maintaining physical capability.
AB  - Research on healthy ageing lacks an agreed conceptual framework and has not
      adequately taken into account the growing evidence that social and biological
      factors from early life onwards affect later health. We conceptualise healthy
      ageing within a life-course framework, separating healthy biological ageing (in
      terms of optimal physical and cognitive functioning, delaying the onset of
      chronic diseases, and extending length of life for as long as possible) from
      changes in psychological and social wellbeing. We summarise the findings of a
      review of healthy ageing indicators, focusing on objective measures of physical
      capability, such as tests of grip strength, walking speed, chair rises and
      standing balance, which aim to capture physical functioning at the individual
      level, assessing the capacity to undertake the physical tasks of daily living.
      There is robust evidence that higher scores on these measures are associated with
      lower rates of mortality, and more limited evidence of lower risk of morbidity,
      and of age-related patterns of change. Drawing on a research collaboration of UK
      cohort studies, we summarise what is known about the influences on physical
      capability in terms of lifetime socioeconomic position, body size and lifestyle,
      and underlying physiology and genetics; the evidence to date supports a broad set
      of factors already identified as risk factors for chronic diseases. We identify a
      need for larger longitudinal studies to investigate age-related change and ethnic
      diversity in these objective measures, the dynamic relationships between them,
      and how they relate to other component measures of healthy ageing. Robust
      evidence across cohort studies, using standardised measures within a clear
      conceptual framework, will benefit policy and practice to promote healthy ageing.

PMID- 24456833
TI  - The depth of post-treatment perirectal tissue invasion is a predictor of outcome
      in patients with clinical T3N1M0 rectal cancer treated with neoadjuvant
      chemoradiation followed by surgical resection.
AB  - BACKGROUND: To determine if patients with clinical stage III rectal cancer
      treated with neoadjuvant chemoradiotherapy (CRT) and surgery have an improved
      survival when the response to treatment results in a pathologic T3 tumor with a
      microscopic focus (<=5 mm) compared with a larger (>5 mm) invasion of the
      perirectal tissue. METHODS: A retrospective review was conducted of 56
      consecutive patients clinically diagnosed as T3N1M0 rectal cancer before
      treatment, who completed neoadjuvant CRT followed by surgical resection. Those
      with residual pathologic T3 disease (n = 28) were analyzed separately.
      Clinicopathologic data including T stage, lymph node status, k-ras status, and
      differentiation were reviewed. RESULTS: Among all 56 patients, there was no
      identified predictor of survival following neoadjuvant CRT and surgery. Among
      those with residual T3 disease, tumors extending >5 mm invasion into the
      perirectal tissue were associated with a higher risk of recurrence (50% vs 17%)
      and worse overall survival (4.3 vs 6.8 years, P = .015) when compared to tumors
      with <=5 mm invasion into the perirectal tissue. CONCLUSION: The depth of
      residual T3 tumor invasion into the perirectal tissue correlates with recurrence
      and overall survival in patients who underwent neoadjuvant therapy followed by
      surgical resection for clinically staged T3N1M0 rectal cancer.

PMID- 24456834
TI  - Development of Young Adults Eating and Active for Health (YEAH) internet-based
      intervention via a community-based participatory research model.
AB  - OBJECTIVE: To develop a tailored, theory-based, Web-delivered intervention to
      prevent excessive weight gain in young adults using a Community-Based
      Participatory Research model. DESIGN: Investigators from 14 universities
      developed the intervention and supporting administrative portal using the 4
      phases of the PRECEDE model. Steering committees were composed of the target
      audience (aged 19-24 years) and key health/wellness personnel were formed at each
      institution and provided information during each phase that was used to guide
      development of the intervention, Project YEAH (Young Adults Eating and Active for
      Health). Piloting results were used to refine the curriculum and identify and
      avoid barriers to delivery. RESULTS: Qualitative and quantitative data collected
      at each phase informed Project YEAH development. In Phase 1, factors of highest
      priority to young adults were identified. In Phase 2, environmental supports for
      healthful lifestyles were elucidated. In Phase 3, behavior and environmental
      changes considered important and changeable were identified. In Phase 4, the 10
      week, theory-based, stage-tailored, interactive-learning intervention with a 10
      month reinforcement period was developed. CONCLUSIONS AND IMPLICATIONS: Applying
      the PRECEDE model with fidelity during development of Project YEAH resulted in an
      intervention that pilot participants found relevant and useful, gained attention,
      instilled confidence in the ability to apply the information, and provided a
      sense of satisfaction.

PMID- 24456835
TI  - Using PRECEDE to develop a weight management program for disadvantaged young
      adults.
AB  - OBJECTIVE: To conduct a needs assessment using the PRECEDE model for the
      development of a weight management program for low-income young adults. DESIGN:
      Four phases were implemented using qualitative (focus groups and interviews) and
      quantitative (survey) methodologies, with steering committee guidance. SETTING:
      Northeastern residential vocational center. PARTICIPANTS: Convenience sample of
      low-income young adults, 18-24 years old (total n = 203), who were attending a
      job training vocational center. PHENOMENON OF INTEREST: General themes of life
      satisfaction determinants and issues related to weight, self-reported weight and
      related behavior, existing environmental supports, and desired changes of
      behavioral and environmental influences of weight. ANALYSIS: Content analysis of
      qualitative data; descriptive analysis and Student t test. RESULTS: Self-image
      and discrimination were themes for weight issues. More than half of participants
      were overweight or obese (57%) and had low levels of physical activity (58%).
      Self-reported fruit and vegetable intake was inadequate (<2.5 cups/d). Identified
      environmental factors most needing improvement were accessibility for walking and
      biking and availability of healthful food. Participants reported exercising,
      getting adequate sleep, eating healthful snacks, and effectively managing stress
      as behavior they were willing to change. CONCLUSIONS AND IMPLICATIONS: The
      PRECEDE model was useful to identify concerns, priorities, and modifiable factors
      among a young adult community that can increase the relevancy of a weight
      management program.

PMID- 24456836
TI  - Enteric repair in aortoduodenal fistulas: a forgotten but often lethal player.
AB  - BACKGROUND: An aortoenteric fistula is an abnormal communication between the
      aorta and the bowel lumen. It is usually caused by previous aortic surgery and
      involves the duodenum (ADF) in most cases. The treatment of this high-mortality
      condition is based on the correction of enteric and vascular defects. However,
      enteric repair indications and impact are unknown. OBJECTIVE: We sought to
      characterize the surgical procedures available for duodenal repair in ADF and
      estimate their impact in mortality. METHODS: A literature search was conducted,
      between the years 1951-2010. Cases (791 from 614 references) were individually
      registered and analyzed to demography, enteric location, type and cause of
      fistula, type of surgical procedure, mortality, and cause of death. Risk factors
      to outcome were estimated by univariate and multivariate analysis. RESULTS: The
      enteric procedure was described in 331 cases: duodenorrhaphy (with or without
      omentum interposition; with or without enterostomy) in 266 cases, duodenal
      resection/reconstruction in 54 cases, antibiotic or abdominal drainage alone in 4
      cases, and nothing was done in 7 cases. Vascular treatment was described in 515
      cases: extra-anatomic bypass in 207 cases, in situ graft in 197 cases, direct
      closure of the aortic defect in 52 cases, endovascular procedures in 32 cases,
      and others arterial reconstructions in 27 cases. Univariate analysis revealed
      that mortality caused by ADF is directly associated with primary ADF type, direct
      closure of the aortic defect, and is inversely associated with recent
      publications, omentum interposition, use of an in situ graft, and endovascular
      prosthesis. Multivariate analysis revealed that omentum interposition and the use
      of an in situ graft were independent factors to the outcome, and that omentum use
      was the strongest factor related to survival. The most common cause of death was
      ADF recurrence (41.8%), which was significantly high (P = 0.036) in the patients
      who underwent simple duodenorrhaphy. CONCLUSIONS: The literature supports the use
      of omentum interposition and suggests that duodenal derivation is preferable to
      the simple closure of fistula. Delayed or avoided enteric repair after
      endovascular treatment emerged as an option, but needs additional supporting
      research.

PMID- 24456837
TI  - Anxiety disorders in adolescents and psychosocial outcomes at age 30.
AB  - BACKGROUND: Anxiety disorders are associated with adverse psychosocial
      functioning, and are predictive of a wide range of psychiatric disorders in
      adulthood. OBJECTIVE: The present study examined the associations between anxiety
      disorders during childhood and adolescence and psychosocial outcomes at age 30,
      and sought to address the extent to which psychopathology after age 19 mediated
      these relations. METHOD: Eight hundred and sixteen participants from a large
      community sample were interviewed twice during adolescence, at age 24, and at age
      30. They completed self-report measures of psychosocial functioning and semi
      structured diagnostic interviews during adolescence and young adulthood. RESULTS:
      Adolescent anxiety predicted poor total adjustment, poor adjustment at work, poor
      family relationships, problems with the family unit, less life satisfaction, poor
      coping skills, and more chronic stress. Adolescent anxiety predicted, substance
      (SUD), alcohol abuse/dependence (AUD), and anxiety in adulthood. No adult
      psychopathology mediated the relationship between childhood anxiety disorders and
      psychosocial outcomes at age 30. Adult, SUD, AUD and anxiety mediated the
      association between adolescent anxiety and most domains of psychosocial
      functioning at age 30. LIMITATIONS: The participants are ethically and
      geographically homogenous, and changes in the diagnostic criteria and the
      interview schedules across the assessment periods. CONCLUSION: Adolescent
      anxiety, compared to childhood anxiety, is associated with more adverse
      psychosocial outcomes at age 30. Adolescent anxiety affects negative outcomes at
      age 30 directly and through adult anxiety, SUD and AUD.

PMID- 24456839
TI  - Second-line therapy for patients with chronic myeloid leukemia resistant to first
      line imatinib.
AB  - The treatment of chronic myeloid leukemia (CML) with BCR-ABL1 tyrosine kinase
      inhibitors (TKIs) is highly effective in reducing disease burden and prolonging
      overall survival in the majority of patients. Up to one-third of patients who
      initiate first-line TKI therapy with imatinib, however, experience resistance to
      treatment, presenting as a lack or loss of response or as disease progression.
      Sokal or Hasford risk score at baseline and achievement of early molecular
      response to treatment may help identify patients at risk for resistance to first
      line TKI therapy and poor prognosis. Approximately half of the patients with
      resistance to TKI treatment have mutations in the BCR-ABL1 kinase domain.
      Mutation status can be informative and should be considered alongside other
      factors, including patient history and drug safety profile, in second-line
      treatment choice. Factors present at the time of initiation of second-line TKI
      therapy, such as response to initial therapy, as well as achievement of molecular
      response within the first 6 months of second-line TKI therapy, have value in
      predicting response and survival outcomes. Given the expanding number of
      therapeutic options currently approved (FDA), an understanding of the clinical
      data supporting each of the options for second-line treatment would enable
      clinicians to develop treatment plans based on the best evidence-based
      information. This review estimates the incidence rate of TKI resistance that
      might be expected in the first-line setting, outlines practical approaches to
      determine TKI resistance, and discusses the factors that clinicians should
      consider when making a second-line treatment choice. 

PMID- 24456842
TI  - Auxology - an editorial.
AB  - Auxology (Greek alphaupsilonxiomega - I let grow) is the science of human growth
      and development. Significant public interest focuses on questions like: how does
      my child grow? How did our ancestors grow? How do other people around the world
      grow? Are there advantages to being tall and disadvantages to being short? Am I
      too fat? And many questions are related to the treatment of growth failure.

PMID- 24456841
TI  - Rapid and simple detection of methicillin-resistance Staphylococcus aureus by
      orfX loop-mediated isothermal amplification assay.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become one of
      the most prevalent pathogens responsible for nosocomial infections throughout the
      world. As clinical MRSA diagnosis is concerned, current diagnostic methodologies
      are restricted by significant drawbacks and novel methods are required for MRSA
      detection. This study aimed at developing a simple loop-mediated isothermal
      amplification (LAMP) assay targeting on orfX for the rapid detection of
      methicillin-resistance Staphylococcus aureus (MRSA). RESULTS: The protocol was
      designed by targeting orfX, a highly conserved open reading frame in S. aureus.
      One hundred and sixteen reference strains, including 52 Gram-positive and 64 Gram
      negative isolates, were included for evaluation and optimization of the orfX-LAMP
      assay. This assay had been further performed on 667 Staphylococcus (566 MRSA, 25
      MSSA, 53 MRCNS and 23 MSCNS) strains and were comparatively validated by PCR
      assay using primers F3 and B3, with rapid template DNA processing, simple
      equipments (water bath) and direct result determination (both naked eye and under
      UV light) applied. The indispensability of each primer had been confirmed, and
      the optimal amplification was obtained under 65 degrees C for 45 min. The 25 MUl
      reactant was found to be the most cost-efficient volume, and the detection limit
      was determined to be 10 DNA copies and 10 CFU/reaction. High specificity was
      observed when orfX-LAMP assay was subjected to 116 reference strains. For
      application, 557 (98.4%, 557/566) and 519 (91.7%, 519/566) tested strains had
      been detected positive by LAMP and PCR assays. The detection rate, positive
      predictive value (PPV) and negative predictive value (NPV) of orfX-LAMP were
      98.4%, 100% and 92.7% respectively. CONCLUSIONS: The established orfX-LAMP assay
      had been demonstrated to be a valid and rapid detection method on MRSA.

PMID- 24456840
TI  - Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level
      (INO2 and INO4) on lipid metabolism in yeast.
AB  - BACKGROUND: In the yeast Saccharomyces cerevisiae, genes containing UASINO
      sequences are regulated by the Ino2/Ino4 and Opi1 transcription factors, and this
      regulation controls lipid biosynthesis. The expression level of INO2 and INO4
      genes (INO-level) at different nutrient limited conditions might lead to various
      responses in yeast lipid metabolism. METHODS: In this study, we undertook a
      global study on how INO-levels (transcription level of INO2 and INO4) affect
      lipid metabolism in yeast and we also studied the effects of single and double
      deletions of the two INO-genes (deficient effect). Using 2 types of nutrient
      limitations (carbon and nitrogen) in chemostat cultures operated at a fixed
      specific growth rate of 0.1 h-1 and strains having different INO-level, we were
      able to see the effect on expression level of the genes involved in lipid
      biosynthesis and the fluxes towards the different lipid components. Through
      combined measurements of the transcriptome, metabolome, and lipidome it was
      possible to obtain a large dataset that could be used to identify how the INO
      level controls lipid metabolism and also establish correlations between the
      different components. RESULTS: In this study, we undertook a global study on how
      INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in
      yeast and we also studied the effects of single and double deletions of the two
      INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and
      nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h
      1 and strains having different INO-level, we were able to see the effect on
      expression level of the genes involved in lipid biosynthesis and the fluxes
      towards the different lipid components. Through combined measurements of the
      transcriptome, metabolome, and lipidome it was possible to obtain a large dataset
      that could be used to identify how the INO-level controls lipid metabolism and
      also establish correlations between the different components. CONCLUSIONS: Our
      analysis showed the strength of using a combination of transcriptome and lipidome
      analysis to illustrate the effect of INO-levels on phospholipid metabolism and
      based on our analysis we established a global regulatory map.

PMID- 24456843
TI  - Uterovaginal anastomosis for complete cervical agenesis and partial vaginal
      agenesis: a case report.

PMID- 24456844
TI  - Gynecologic laparoscopy in patients aged 65 or more: feasibility and safety in
      the presence of increased comorbidity.
AB  - OBJECTIVES: To evaluate the feasibility, operative outcome and postoperative
      complications of laparoscopic gynaecologic surgery in patients aged 65 or more,
      with increased comorbidity and obesity. STUDY DESIGN: The medical records of
      patients aged 65 or more with uterine or ovarian disease admitted to minimally
      invasive gynecologic surgery units from January 2009 to December 2011 were
      retrospectively analyzed in an observational cohort study. Surgical outcomes of
      the laparoscopic cohort (n=65) were compared with the outcomes of those who had
      laparotomy (n=67) at general gynecologic surgery units, and evaluated with
      respect to indication for surgery, medical comorbidity and obesity. Laparoscopic
      surgery was attempted in women who accepted minimally invasive management and who
      had no absolute contraindications to laparoscopy. Surgical inclusion criteria
      were benign and malignant uterine and adnexal pathologies; benign uterine
      pathologies when uterine size was less than 18 weeks' gestation or myoma smaller
      than 10cm; malignancies in apparent early-stage disease. There was no attempt to
      use laparoscopy for tumor debulking and cytoreductive surgery. Exclusion criteria
      were patients with emergency operations or a concomitant urogynecologic
      procedure. Data were analyzed using Student's t-test, the Mann-Whitney U test,
      chi(2) testing and the Fisher exact test. RESULTS: Patients undergoing
      laparoscopy had a significantly shorter hospital stay (p<0.001), less
      intraoperative bleeding (p<0.001), less postoperative hemoglobin decline
      (p<0.001), less need for blood transfusions (p=0.007) and a generally lower
      incidence of complications compared to women who had laparotomy, regardless of
      medical comorbidity. Obese patients who had laparoscopy had significantly less
      intraoperative bleeding and a smaller postoperative hemoglobin drop; no
      adjunctive complication was observed. In patients over 70 (80 cases) the
      laparoscopic group (39 cases) maintained significantly less intraoperative
      bleeding (p<0.001) and a smaller hemoglobin drop (p<0.001) with respect to
      laparotomy, with few postoperative complications. CONCLUSIONS: According to the
      results of the study, laparoscopic surgery appears feasible and safe in elderly
      patients, regardless of medical comorbidity and obesity.

PMID- 24456845
TI  - The fractalkine/Cx3CR1 system is implicated in the development of metabolic
      visceral adipose tissue inflammation in obesity.
AB  - Diet-induced obesity and related peripheral and central inflammation are major
      risk factors for metabolic, neurological and psychiatric diseases. The chemokine
      fractalkine (Cx3CL1) and its receptor Cx3CR1 play a pivotal role in recruitment,
      infiltration and proinflammatory polarization of leukocytes and micoglial cells,
      however, the role of fractalkine signaling in the development of metabolic
      inflammation is not fully resolved. To address this issue, fractalkine receptor
      deficient (Cx3CR1 gfp/gfp) mice were exposed to normal or fat-enriched diet
      (FatED) for 10weeks and physiological-, metabolic- and immune parameters were
      compared to those animals in which the fractalkine signaling is maintained by the
      presence of one functioning allele (Cx3CR1 +/gfp). Mice with intact fractalkine
      signaling develop obesity characterized by increased epididymal white fat depots
      and mild glucose intolerance, recruit leukocytes into the visceral adipose tissue
      and display increased expression of subset of pro- and anti-inflammatory
      cytokines when exposed to fat-enriched diet. By contrast, Cx3CR1-deficient
      (gfp/gfp) mice gain significantly less weight on fat-enriched diet and have
      smaller amount of white adipose tissue (WAT) in the visceral compartment than
      heterozygote controls. Furthermore, Cx3CR1 gfp/gfp mice fed a fat-enriched diet
      do not develop glucose intolerance, recruit proportionally less number of gfp
      positive cells and express significantly less MCP-1, IL-1alpha and TNFalpha in
      the WAT than control animals with fat-enriched diet induced obesity. Furthermore,
      heterozygote obese, but not fractalkine receptor deficient mice express high
      levels of anti-inflammatory IL-10 and arginase1 markers in the visceral fat. The
      effect of fat-enriched diet on cytokine expression pattern was specific for the
      WAT, as we did not detect significant elevation of interleukin-1, tumor necrosis
      factor-alpha and monocyte chemotacting protein (MCP-1) expression in the liver or
      in the hypothalamus in either genotype. These results highlight the importance of
      fractalkine signaling in recruitment and polarization of adipose tissue immune
      cells and identify fractalkine as a target to fight obesity-induced inflammatory
      complications. 

PMID- 24456846
TI  - Elevated C-reactive protein levels may be a predictor of persistent unfavourable
      symptoms in patients with mild traumatic brain injury: a preliminary study.
AB  - The pathogenesis of persistent unfavourable outcomes following mild traumatic
      brain injury (mTBI) are not fully understood. Low-grade systemic inflammation
      might contribute to the development of persistent unfavourable outcomes in
      patients with mTBI. We used plasma high-sensitivity C-reactive protein (CRP)
      levels as the biomarker of systemic inflammation to investigate whether elevated
      CRP levels were associated with persistent adverse outcomes in these patients. A
      total of 213 consecutive patients with mTBI were identified in our study. Plasma
      high-sensitivity CRP levels were measured at baseline, 1month, 2months and
      3months after initial traumatic brain injury. The study endpoints included
      persistent postconcussion syndrome (PCS), persistent psychological problems
      (depression and anxiety), persistent physiological problems (frequent headache,
      nausea, insomnia, dizziness and fatigue) and persistent cognitive impairment,
      which were screened by International Classification of Diseases (ICD-10),
      diagnostic and statistical manual of mental disorders (DSM-IV), Beck anxiety
      inventory (BAI), Beck depression inventory (BDI) and montreal cognitive
      assessment (MoCA) 3months post-injury. The associations between baseline CRP
      levels and persistent unfavourable outcomes were estimated from multiple
      regression models adjusting for various confounding covariates. Elevated baseline
      CRP levels were associated with a significant increase in the incidence of
      persistent PCS (odds ratio [OR], 2.719; 95% confidence interval [CI], 1.609
      4.594; p=0.000), persistent psychological problems (OR, 1.535; 95% CI, 1.063
      2.216; p=0.022), and persistent cognitive impairment (OR, 1.687; 95% CI, 1.135
      2.507; p=0.010). However, elevated CRP levels were not associated with persistent
      physiological problems (OR, 1.330; 95% CI, 0.905-1.956; p=0.146). Furthermore,
      three adjusted models did not essentially affect the OR of elevated CRP levels
      for these persistent unfavourable outcomes. Among patients with mTBI, baseline
      elevated CRP levels may be an independent predictor of persistent persistent PCS,
      psychological problems and cognitive impairment. 

PMID- 24456847
TI  - Comprehension and acceptability of on-board traffic information: Beliefs and
      driving behaviour.
AB  - Co-Drive on-board traffic information system is a complementary tool providing a
      dynamic management of transportation infrastructure and traffic as well as the
      diffusion of accurate real-time information about the road environment and
      motorists' driving behaviour. The aim of this study was to examine drivers'
      acceptability of Co-Drive by investigating the impact of traffic information
      provided via on-board display devices on motorists' beliefs and behaviour. 116
      drivers (Men=46.6%), between 22 and 62 years, participated to a driving simulator
      experiment. They were randomly divided into two experimental groups according to
      the type of display device (Blackberry vs. iPhone) and a control group. The
      experimental groups were exposed to fourteen on-board traffic messages: warning
      (e.g., road crash), recommendation (e.g., the use of seat-belt) and comfort
      messages (e.g., the location of a gas station). They had to validate each message
      by pushing the headlight flashing button as soon as they understood it. At the
      end, all participants had to fill in a questionnaire. Drivers evaluated
      positively the on-board messages, expressed a high level of confidence in the on
      board information and estimated having received it sufficiently in advance for
      them to adjust their behaviour. Regardless of the type of display device, they
      took more time to read warning and recommendation messages as compared to comfort
      messages and complied with them. Finally, those exposed to the messages adapted
      their behaviour easier to the road events than those who did not receive them.
      Practical implications of the results are discussed. 

PMID- 24456848
TI  - Prevalence of alcohol-impaired drivers based on random breath tests in a roadside
      survey in Catalonia (Spain).
AB  - Sobriety checkpoints are not usually randomly located by traffic authorities. As
      such, information provided by non-random alcohol tests cannot be used to infer
      the characteristics of the general driving population. In this paper a case study
      is presented in which the prevalence of alcohol-impaired driving is estimated for
      the general population of drivers. A stratified probabilistic sample was designed
      to represent vehicles circulating in non-urban areas of Catalonia (Spain), a
      region characterized by its complex transportation network and dense traffic
      around the metropolis of Barcelona. Random breath alcohol concentration tests
      were performed during spring 2012 on 7596 drivers. The estimated prevalence of
      alcohol-impaired drivers was 1.29%, which is roughly a third of the rate obtained
      in non-random tests. Higher rates were found on weekends (1.90% on Saturdays and
      4.29% on Sundays) and especially at night. The rate is higher for men (1.45%)
      than for women (0.64%) and it shows an increasing pattern with age. In vehicles
      with two occupants, the proportion of alcohol-impaired drivers is estimated at
      2.62%, but when the driver was alone the rate drops to 0.84%, which might reflect
      the socialization of drinking habits. The results are compared with outcomes in
      previous surveys, showing a decreasing trend in the prevalence of alcohol
      impaired drivers over time. 

PMID- 24456849
TI  - Analysis of factors associated with injury severity in crashes involving young
      New Zealand drivers.
AB  - Young people are a risk to themselves and other road users, as motor vehicle
      crashes are the leading cause of their death. A thorough understanding of the
      most important factors associated with injury severity in crashes involving young
      drivers is important for designing well-targeted restrictive measures within
      youth-oriented road safety programs. The current study estimates discrete choice
      models of injury severity of crashes involving young drivers conditional on these
      crashes having occurred. The analysis examined a comprehensive set of single
      vehicle and two-vehicle crashes involving at least one 15-24 year-old driver in
      New Zealand between 2002 and 2011 that resulted in minor, serious or fatal
      injuries. A mixed logit model accounting for heterogeneity and heteroscedasticity
      in the propensity to injury severity outcomes and for correlation between serious
      and fatal injuries proved a better fit than a binary and a generalized ordered
      logit. Results show that the young drivers' behavior, the presence of passengers
      and the involvement of vulnerable road users were the most relevant factors
      associated with higher injury severity in both single-vehicle and two-vehicle
      crashes. Seatbelt non-use, inexperience and alcohol use were the deadliest
      behavioral factors in single-vehicle crashes, while fatigue, reckless driving and
      seatbelt non-use were the deadliest factors in two-vehicle crashes. The presence
      of passengers in the young drivers' vehicle, and in particular a combination of
      males and females, dramatically increased the probability of serious and fatal
      injuries. The involvement of vulnerable road users, in particular on rural
      highways and open roads, considerably amplified the probability of higher crash
      injury severity. 

PMID- 24456851
TI  - Validation of a full-scale membrane bioreactor and the impact of membrane
      cleaning on the removal of microbial indicators.
AB  - The removal of microbial indicators through a full-scale membrane bioreactor
      (MBR) was characterised. The overall log reduction of Escherichia coli and total
      coliforms were in the range of 5.0-5.9log10 units, while the reduction of
      clostridia was marginally less at 4.9log10 units. Removal of bacteriophage was in
      excess of 4.6log10 units. The impact of membrane cleaning on the elimination of
      microbial indicators was also assessed since this had been identified by pilot
      scale studies as a potential hazardous event. Membrane cleaning temporarily
      reduced the log removal values of E. coli and total coliforms each by 1log10
      unit, but did not affect the removal of bacteriophage or clostridia. Very little
      research has previously examined the consequences of hazardous events on the
      performance of full-scale MBRs, and thus the findings presented here will
      facilitate improvements for the risk assessment and management of MBRs used in
      water recycling schemes. 

PMID- 24456853
TI  - The larvae of congeneric gastropods showed differential responses to the combined
      effects of ocean acidification, temperature and salinity.
AB  - The tolerance and physiological responses of the larvae of two congeneric
      gastropods, the intertidal Nassarius festivus and subtidal Nassarius conoidalis,
      to the combined effects of ocean acidification (pCO2 at 380, 950, 1250 ppm),
      temperature (15, 30 degrees C) and salinity (10, 30 psu) were compared. Results
      of three-way ANOVA on cumulative mortality after 72-h exposure showed significant
      interactive effects in which mortality increased with pCO2 and temperature, but
      reduced at higher salinity for both species, with higher mortality being obtained
      for N. conoidalis. Similarly, respiration rate of the larvae increased with
      temperature and pCO2 level for both species, with a larger percentage increase
      for N. conoidalis. Larval swimming speed increased with temperature and salinity
      for both species whereas higher pCO2 reduced swimming speed in N. conoidalis but
      not N. festivus. The present findings indicated that subtidal congeneric species
      are more sensitive than their intertidal counterparts to the combined effects of
      these stressors.

PMID- 24456852
TI  - Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation
      and whole body inhalation: the effect of dose rate on acute respiratory tract
      inflammation.
AB  - BACKGROUND: The increased production of nanomaterials has caused a corresponding
      increase in concern about human exposures in consumer and occupational settings.
      Studies in rodents have evaluated dose-response relationships following
      respiratory tract (RT) delivery of nanoparticles (NPs) in order to identify
      potential hazards. However, these studies often use bolus methods that deliver
      NPs at high dose rates that do not reflect real world exposures and do not
      measure the actual deposited dose of NPs. We hypothesize that the delivered dose
      rate is a key determinant of the inflammatory response in the RT when the
      deposited dose is constant. METHODS: F-344 rats were exposed to the same
      deposited doses of titanium dioxide (TiO2) NPs by single or repeated high dose
      rate intratracheal instillation or low dose rate whole body aerosol inhalation.
      Controls were exposed to saline or filtered air. Bronchoalveolar lavage fluid
      (BALF) neutrophils, biochemical parameters and inflammatory mediator release were
      quantified 4, 8, and 24 hr and 7 days after exposure. RESULTS: Although the
      initial lung burdens of TiO2 were the same between the two methods, instillation
      resulted in greater short term retention than inhalation. There was a
      statistically significant increase in BALF neutrophils at 4, 8 and 24 hr after
      the single high dose TiO2 instillation compared to saline controls and to TiO2
      inhalation, whereas TiO2 inhalation resulted in a modest, yet significant,
      increase in BALF neutrophils 24 hr after exposure. The acute inflammatory
      response following instillation was driven primarily by monocyte chemoattractant
      protein-1 and macrophage inflammatory protein-2, mainly within the lung.
      Increases in heme oxygenase-1 in the lung were also higher following instillation
      than inhalation. TiO2 inhalation resulted in few time dependent changes in the
      inflammatory mediator release. The single low dose and repeated exposure
      scenarios had similar BALF cellular and mediator response trends, although the
      responses for single exposures were more robust. CONCLUSIONS: High dose rate NP
      delivery elicits significantly greater inflammation compared to low dose rate
      delivery. Although high dose rate methods can be used for quantitative ranking of
      NP hazards, these data caution against their use for quantitative risk
      assessment.

PMID- 24456854
TI  - The environmental release and fate of antibiotics.
AB  - Antibiotics have been used as medical remedies for over 50 years and have
      recently emerged as new pollutants in the environment. This review encompasses
      the fate of several antibiotics in the environment, including sulfonamides,
      nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the
      cycle of transfer from humans and animals including their metabolic
      transformation. The results show that antibiotic metabolites are of considerable
      persistence and are localized to ground-water and drinking water supplies.
      Furthermore, the results also show that several phases of the cycle of
      antibiotics in the environment are not well understood, such as how low
      concentrations of antibiotic metabolites in the diet affect humans and animals.
      This review also shows that improved wastewater decontamination processes are
      remediating factors for these emerging pollutants. The results obtained here may
      help legislators and authorities in understanding the fate and transformation of
      antibiotics in the environment.

PMID- 24456850
TI  - Corticotropin releasing factor: a key role in the neurobiology of addiction.
AB  - Drug addiction is a chronically relapsing disorder characterized by loss of
      control over intake and dysregulation of stress-related brain emotional systems.
      Since the discovery by Wylie Vale and his colleagues of corticotropin-releasing
      factor (CRF) and the structurally-related urocortins, CRF systems have emerged as
      mediators of the body's response to stress. Relatedly, CRF systems have a
      prominent role in driving addiction via actions in the central extended amygdala,
      producing anxiety-like behavior, reward deficits, excessive, compulsive-like drug
      self-administration and stress-induced reinstatement of drug seeking. CRF neuron
      activation in the medial prefrontal cortex may also contribute to the loss of
      control. Polymorphisms in CRF system molecules are associated with drug use
      phenotypes in humans, often in interaction with stress history. Drug discovery
      efforts have yielded brain-penetrant CRF1 antagonists with activity in
      preclinical models of addiction. The results support the hypothesis that brain
      CRF-CRF1 systems contribute to the etiology and maintenance of addiction. 

PMID- 24456855
TI  - Organotin contamination in seafood and its implication for human health risk in
      Hong Kong.
AB  - Organotins (OTs) have caused widespread adverse effects on marine organisms,
      while they can also induce health problems to humans via consumption of
      contaminated seafood. This study aimed to quantify the tissue concentrations of
      OTs in 11 seafood species in Hong Kong, and assess the human health risk for
      consuming these species. The tongue sole Paraplagusia blochii had the highest
      concentration of total OTs. Triphenyltin (TPT) accounted for 56-97% of total OTs.
      The highest hazard quotient (HQ) for TPT was 1.41 in P. blochii, while the HQs
      for butyltins were much less than 1. The results indicated that it is likely to
      have certain health risks for consuming P. blochii due to its high TPT
      contamination. Therefore, TPT should be a priority pollutant of concern.
      Appropriate management actions should be taken to control its use and release in
      the region in order to safeguard the marine ecosystem and human health. 

PMID- 24456856
TI  - Impacts of Macondo oil from Deepwater Horizon spill on the growth response of the
      common reed Phragmites australis: a mesocosm study.
AB  - We investigated impacts of Macondo MC252 oil from the Deepwater Horizon (DWH)
      spill on the common reed Phragmites australis (Cav.) Trin. ex Steud., a dominant
      species of the Mississippi River Delta. In greenhouse experiments, we simulated
      the most common DWH oiling scenarios by applying weathered and emulsified Macondo
      oil to aboveground shoots at varying degrees of coverage (0-100%) or directly to
      marsh soil at different dosages (0-16 Lm(-)(2)). P. australis exhibited strong
      resistance to negative impacts when oil was applied to shoots alone, while
      reductions in above- and belowground plant growth were apparent when oil was
      applied to the soil or with repeated shoot-oiling. Although soil-oiling
      compromised plant function, mortality of P. australis did not occur. Our results
      demonstrate that P. australis has a high tolerance to weathered and emulsified
      Macondo oil, and that mode of exposure (aboveground versus belowground) was a
      primary determinant of impact severity.

PMID- 24456857
TI  - Optogenetic activation of GABAergic neurons in the nucleus accumbens decreases
      the activity of the ventral pallidum and the expression of cocaine-context
      associated memory.
AB  - GABAergic medium-sized spiny neurons (MSNs) in the nucleus accumbens (NAc)
      differentially express D1 and D2 dopamine receptors. Both D2- and D1-MSNs in the
      NAc form projections into the ventral pallidum, whereas only D1-MSNs directly
      project into midbrain neurons. They are critical in rewarding and aversive
      learning, and understanding the function of these NAc efferents and the
      alteration of their targeted brain regions in responding to a reward-associated
      context is important. In this study, we activated the GABAergic neurons in the
      NAc of mice expressing channelrhodopsin-2 under the control of the vesicular GABA
      transporter promoter by an optogenetic approach, and examined its effects on the
      expression of cocaine-context-associated memory. In vivo optogenetic activation
      of the NAc GABAergic neurons inhibited the expression of cocaine-conditioned
      place preference (CPP). When tested 24 h later, these mice exhibited normal
      cocaine-induced CPP, indicating that the inhibitory effect on the expression of
      CPP was transient and reversible. Activation of the NAc GABAergic neurons also
      attenuated the learning of cocaine-induced reinforcement, as indicated by the
      results of behavioural sensitization. To explore how the cocaine-context
      associated information was processed and integrated, we assessed the activity of
      NAc MSN-targeted brain nuclei and found that the activation of NAc GABAergic
      neurons during CPP expression resulted in a decrease of c-Fos+ cells in the
      ventral palladium. Our data suggested that the NAc GABAergic efferents inhibit
      the ventral palladium activity and negatively regulate the expression of
      motivational effects induced by cocaine-context-associated cues.

PMID- 24456858
TI  - Rasch analysis of a Spanish language-screening parent survey.
AB  - The purpose of this study was to evaluate and refine items from a parent survey
      designed to screen the language skills of Spanish-speaking preschoolers. This
      investigation applied Rasch modeling to systematically evaluate and identify
      items that demonstrated favorable qualities. A set of 124 parent survey items was
      administered to 107 Spanish-speaking parents of preschool age children. Parents
      completed survey items intended to provide a global measure of preschool language
      abilities. Rasch analyses of the survey items were conducted using WINSTEPS.
      Results indicated that 59 items, all vocabulary items, fit the Rasch model.
      Sufficient unidimensionality was obtained, with the model accounting for 58% of
      the variance. Item difficulty estimates ranged from -7.43 to 4.12, with a
      shortage of items at both the lower ability level and at the higher ability
      level. Analyses of pruned and remaining items identified the type of items that
      may be most useful for a refined item bank. These results will inform the
      development of new items for a Spanish language-screening parent survey for
      preschool age children. 

PMID- 24456859
TI  - Exploring metabolism flexibility in complex organisms through quantitative study
      of precursor sets for system outputs.
AB  - BACKGROUND: When studying metabolism at the organ level, a major challenge is to
      understand the matter exchanges between the input and output components of the
      system. For example, in nutrition, biochemical models have been developed to
      study the metabolism of the mammary gland in relation to the synthesis of milk
      components. These models were designed to account for the quantitative
      constraints observed on inputs and outputs of the system. In these models, a
      compatible flux distribution is first selected. Alternatively, an infinite family
      of compatible set of flux rates may have to be studied when the constraints
      raised by observations are insufficient to identify a single flux distribution.
      The precursors of output nutrients are traced back with analyses similar to the
      computation of yield rates. However, the computation of the quantitative
      contributions of precursors may lack precision, mainly because some precursors
      are involved in the composition of several nutrients and because some metabolites
      are cycled in loops. RESULTS: We formally modeled the quantitative allocation of
      input nutrients among the branches of the metabolic network (AIO). It corresponds
      to yield information which, if standardized across all the outputs of the system,
      allows a precise quantitative understanding of their precursors. By solving
      nonlinear optimization problems, we introduced a method to study the variability
      of AIO coefficients when parsing the space of flux distributions that are
      compatible with both model stoichiometry and experimental data. Applied to a
      model of the metabolism of the mammary gland, our method made it possible to
      distinguish the effects of different nutritional treatments, although it cannot
      be proved that the mammary gland optimizes a specific linear combination of flux
      variables, including those based on energy. Altogether, our study indicated that
      the mammary gland possesses considerable metabolic flexibility. CONCLUSION: Our
      method enables to study the variability of a metabolic network with respect to
      efficiency (i.e. yield rates). It allows a quantitative comparison of the
      respective contributions of precursors to the production of a set of nutrients by
      a metabolic network, regardless of the choice of the flux distribution within the
      different branches of the network.

PMID- 24456861
TI  - Distinctive renal cell tumor simulating atrophic kidney with 2 types of
      microcalcifications. Report of 3 cases.
AB  - We report 3 cases of primary renal cell tumor simulating atrophic kidney with
      distinct gross, morphologic, immunohistochemical, and molecular genetic features.
      The tumors were retrieved out of more than 17 000 renal tumors from the Plzen
      Tumor Registry. Tissues for light microscopy had been fixed, embedded, and
      stained with hematoxylin and eosin using routine procedures. The tumors were
      further analyzed using immunohistochemistry, array comparative genomic
      hybridization, and human androgen receptor. Analyses of VHL gene and loss of
      heterozygosity (LOH) 3p were also performed. The patients were 2 women and 1 man,
      with ages ranging from 29 to 35 years (mean, 31.3 years). Grossly, the neoplasms
      were encapsulated and round with largest diameter of 3.5 cm (mean, 3.2 cm).
      Follow-up available for all patients ranged from 2 to 14 years (mean, 8 years).
      No aggressive behavior was noted. Histologically, akin to atrophic
      (postpyelonephritic) kidney parenchyma, the tumors were composed of follicles of
      varying sizes that were filled by eosinophilic secretion. Rare areas contained
      collapsed follicles. Each follicle was endowed with a small capillary. The stroma
      was loose, inconspicuous, and focally fibrotic. Two types of calcifications were
      noted: typical psammoma bodies and amorphous dark-blue stained calcified
      deposits. Immunohistochemically, tumors were strongly positive for cytokeratins
      (OSCAR), CD10, and vimentin, with weak immunopositivity for CAM5.2 and AE1-AE3.
      WT1 and cathepsin K were weakly to moderately focally to diffusely positive.
      Tumors were negative for cytokeratin 20, carbonic anhydrase IX, parvalbumin,
      HMB45, TTF1, TFE3, chromogranin A, thyroglobulin, PAX8, and ALK. Only 1 case was
      suitable for molecular genetic analyses. No mutations were found in the VHL gene;
      no methylation of VHL promoter was noted. No numerical aberrations were found by
      array comparative genomic hybridization analysis. LOH for chromosome 3p was not
      detected. Analysis of clonality (human androgen receptor) revealed the monoclonal
      nature of the tumor. We describe an unknown tumor of the kidney that (1)
      resembles renal atrophic kidney or nodular goiter of thyroidal gland; (2)
      contains a leiomyomatous capsule and 2 types of calcifications; (3) lacks
      mitoses, atypias, necroses, and hemorrhages and nearly lack Ki-67 positivity; and
      (4) so far showed benign biological behavior. 

PMID- 24456862
TI  - Effective compression bandage for repair of a complicated radial artery
      pseudoaneurysm.
AB  - We describe a 10-week-old hemophilic infant who developed a large-sized
      pseudoaneurysm of the radial artery after arterial puncture. Based on our
      previous experience, compression bandage was elected as first-line treatment. The
      clinical course was complicated by skin ulceration. However, compression bandage
      was continued, and complete thrombosis of the pseudoaneurysm occurred after 4
      weeks of treatment, preserving arterial patency. Bedside clot evacuation and
      enzymatic debridement promoted rapid wound healing with negligible scar
      formation. Compression bandage is a safe and valuable measure for repair of
      radial artery pseudoaneurysm, even in patients with clotting disorders.
      Professionals are encouraged to consider the benefit of such an artery-sparing
      treatment option. 

PMID- 24456863
TI  - Paraincisional subcutaneous infusion of ropivacaine after open abdominal vascular
      surgery shows significant advantages.
AB  - BACKGROUND: Opiates are widely used for postoperative pain relief. Unfortunately,
      their side effects such as inhibited gastrointestinal motility and respiratory
      depression may compromise or delay postoperative recovery after laparotomy. We
      used paraincisional subcutaneous catheters (PSCs) and applied 0.25% ropivacaine
      infusion to improve pain relief and decrease postoperative morphine consumption
      in patients after open surgery for aortic aneurysm. METHODS: A retrospective
      single-center study including 58 patients treated by open surgery for aortic
      aneurysm between October 2006 and June 2012. Overall, 28 patients (control group)
      received standard postoperative pain management including opiates, and 30
      patients (PSC group) were treated with paraincisional continuous local analgesia
      with 0.25% ropivacaine administrated via bilateral subcutaneous catheters along
      with additional ad libitum opiates administration, at first intravenously and
      then orally. RESULTS: Patients characteristics as well as perioperative and
      postoperative outcomes were comparable between the groups during the first 5 days
      after surgery. Patients of the PSC group received significantly less morphine,
      although the patients in both groups reported a similar pain intensity. Neither
      wound-healing disorder nor catheter-associated subcutaneous infection was
      reported. High serum concentration of ropivacaine was detected in 2 patients (6%)
      with end-stage renal disease, who developed temporary neurologic symptoms. Length
      of intensive care unit (ICU) stay was significantly shorter in the PSC group (2
      [0-23] vs. 4.5 [0-32] ICU days). CONCLUSIONS: This is the first report about PSCs
      for analgesia after laparotomy. This case/control study shows that continuous
      paraincisional subcutaneous infusion of 0.25% ropivacaine after open surgery for
      aortic aneurysm repair is a feasible method of postoperative analgesia. This
      technique allows sustained pain relief with significant reduction of opiate
      requirement and faster recovery after surgery. Prospective randomized controlled
      trial is necessary for the assessment of safety and efficacy of this method.

PMID- 24456864
TI  - Cholesterol crystal embolism and delayed-onset paraplegia after thoracoabdominal
      aneurysm repair.
AB  - Postoperative paraplegia caused by ischemic injury of the spinal cord is the most
      disabling complication of thoracoabdominal surgery. We described the case of a 75
      year-old patient who underwent a thoracoabdominal aneurysm repair (type IV
      aneurysm according to Crawford classification). The aorta clamping was done at
      the T11 level without specific medullary protection. The first postoperative week
      was uneventful. On the postoperative day 8, renal failure and livedo of the left
      lower limb occurred together with complete hypotonic paraplegia and severe
      sepsis. Exploratory laparotomy revealed a gangrenous cholecystitis, and skin
      biopsies showed cholesterol crystals embolisms in the hypodermis small arteries.
      The patient died on the postoperative day 28 from a multiorgan failure. In this
      case, paraplegia was due to cholesterol crystal embolism, which migrated
      secondarily after aortic clamping. 

PMID- 24456865
TI  - CT angiography-derived duplex ultrasound velocity criteria in patients with
      carotid artery stenosis.
AB  - BACKGROUND: Validation of carotid duplex ultrasound velocity criteria (CDUS VC)
      to grade the severity of extracranial carotid artery stenosis has traditionally
      been based on conventional angiography measurements. In the last decade, computed
      tomographic angiography (CTA) has largely replaced conventional arch and carotid
      arteriography (CA) for diagnostic purposes. Given the low number of CA being
      performed, it is impractical to expect noninvasive vascular laboratories to be
      validated using this modality. CDUS VC have not been developed with the use of
      CTA-derived measurements. The objective was to determine optimal CDUS VC from CTA
      derived measurements with the North American Symptomatic Carotid Endarterectomy
      Trial (NASCET) method for 50% and 80% stenosis. METHODS: A retrospective review
      of all patients who underwent CDUS and CTA from 2000 to 2009 was performed.
      Vessel diameters were measured on CTA, and corresponding CDUS velocities were
      recorded. Percent stenosis was calculated using the NASCET method. Receiver
      operating characteristic (ROC) curves were generated for internal carotid artery
      (ICA) peak systolic velocity (PSV), ICA end diastolic velocity (EDV), and ICA PSV
      to common carotid artery PSV ratio (PSVR) for 50% and 80% stenosis. Velocity cut
      points were determined with equal weighting of sensitivity and specificity.
      RESULTS: A total of 575 vessels were analyzed to create the ROC curves. A 50%
      stenosis analysis yielded ideal cut points for PSV, EDV, and PSVR of 130 cm/sec,
      42 cm/sec, and 1.75. An 80% stenosis analysis yielded ideal cut points for PSV,
      EDV, and PSVR of 297 cm/sec, 84 cm/sec, and 3.06. CONCLUSIONS: CTA-derived CDUS
      VC appeared to be reliable in defining 50% and 80% stenosis in patients with
      carotid artery stenosis. Although CDUS VC defined in this study were different
      from many of the previously published VC for the same percent stenosis, there
      were many similarities to those reported by the Society of Radiologists in
      Ultrasound consensus conference. We feel that CTA should be the gold standard
      imaging technique for validating CDUS VC.

PMID- 24456866
TI  - Anomalous origin of bilateral vertebral arteries from the ICA: review of the
      literature and a case report.
AB  - Atypical origins of the vertebral arteries (VAs) are rare anatomic findings. In
      this study, we present an extremely rare arrangement of the cerebral circulation
      in a 72-year-old male patient. The anatomic rarity, which was detected using
      ultrasonic imaging, involved the bilateral VAs coming off the internal carotid
      arteries (ICAs). Because the ICA and VA on the left side were severely stenotic,
      the vascular surgeons performed carotid and vertebral endarterectomy
      simultaneously. Although stenosis can be eliminated from these arteries, this
      type of rare anatomy results in more difficulties and risks for the patient.
      Ultrasound imaging provides high anatomic detail during this unique operation. 

PMID- 24456867
TI  - Extrahepatic portal vein aneurysm.
AB  - Portal vein aneurysms (PVAs) are usually incidental on imaging and asymptomatic.
      If it is symptomatic or associated with a pathologic finding, a treatment is
      recommended. We report a case of a 75-year-old Caucasian man presenting with
      symptomatic and size-increasing portosplenomesenteric aneurysms. Interventional
      radiology was not indicated because of the large size. A surgical approach was
      chosen for the patient. Surgical technique consists of an aneurysmorrhaphy in the
      first time and in the second time, a Goretex prosthesis placement involving the
      vein. Early complication was treated with a radiologic approach. Six months after
      surgery, patient had no more symptoms. PVA management remains a surgical
      challenge for surgeon, for timing and type of treatment. 

PMID- 24456868
TI  - Discrepancies in the primary PLATO trial publication and the FDA reviews.
AB  - The results of major indication seeking Phase 3 clinical trials are reported at
      international meetings, and simultaneously published In top medical journals.
      However, the data presented during such dual release do not disclose all the
      trial findings, suffer from overoptimistic interpretations heavily favoring the
      study sponsor. Ironically, after the New Drug Application is submitted for
      regulatory approval, and when the FDA secondary reviews become available for
      public, the benefit/risk assessment of a new drug is usually considered much less
      impressive. However, the community may ignore pivotal unreported findings later
      outlined in the government documents taking for granted the facts presented in
      the primary publication. The discrepancies between initial publication and the
      FDA files are not only confusing to the readership, but hold additional risks for
      patients. Indeed, if physicians are impressed with the initial interpretation of
      the trial, and do not have broad access to the FDA verified facts, chances are
      new agents will be prescribed based on exaggerated benefit and less safety
      concerns. The current pattern also hurts the reputation of the journal
      publishers, editors and reviewers challenging their trust and credibility. We
      here outline the disparity between the primary PLATO trial publication in the New
      England Journal of Medicine against the FDA verified numbers, and discuss how to
      avoid such mismatches in the future. 

PMID- 24456869
TI  - Left ventricular ejection fraction overcrossing 35% after one year of cardiac
      resynchronization therapy predicts long term survival and freedom from sudden
      cardiac death: single center observational experience.
AB  - BACKGROUND: Reverse remodeling and increased LVEF after CRT correlate with
      survival and heart failure hospitalizations, but their relationship with the risk
      of SCD is unclear. We aimed to evaluate whether exceeding a threshold value of
      35% for left ventricular ejection fraction (LVEF) 1 year after cardiac
      resynchronization therapy (CRT) predicts survival and freedom from sudden cardiac
      death (SCD). METHODS: 330 patients who survived >= 6 months after CRT (males 80%,
      age 62 +/- 11 years) were grouped according to 1-year LVEF <= 35% (Group 1,
      n=187, 57%) or >35% (Group 2, n=143, 43%). According to changes vs. baseline
      (reduction of left end-systolic volume [LVESV] >= 10% or increase of LVEF% > 10
      units), patients were also classified as echocardiographic (Echo) non-responders
      (Group A, n=152, 46%) or responders (Group B, n=178, 54%). RESULTS: At baseline,
      LVESV volume was larger and LVEF was lower in Group 1 vs. Group 2 (p<0.001).
      After 1 year, echocardiographic improvement was greater in Group 2 vs. Group 1
      (p<0.001 for changes in both LVESV and LVEF). Over a median follow-up of 49
      months, 47 patients (14%) died, 36 in Group 1 vs. 11 in Group 2 (19% vs. 8%,
      p=0.004). A significantly higher rate of freedom from all-cause mortality
      (p=0.002), cardiovascular mortality (p<0.001) and SCD (p<0.001) was observed in
      Group 2. Multivariate analysis demonstrated that only 1-year LVEF >35% was
      associated with freedom from SCD/VF. CONCLUSIONS: LVEF >35% after 1 year of CRT
      characterizes a favorable long-term outcome, with a very low risk for SCD.

PMID- 24456870
TI  - Paraoxonase 1 (PON1) genotype associated with heart rate variability (HRV) in
      workers.

PMID- 24456871
TI  - Heme iron intake and acute myocardial infarction: a prospective study of men.
AB  - BACKGROUND: Epidemiologic studies of heme iron and non-heme iron intake in
      relation to risk of acute myocardial infarction (AMI) are lacking. Therefore, we
      examine the associations between heme iron and non-heme iron intake and fatal and
      nonfatal AMI in men. Moreover, we investigated whether the associations were
      modified by intake of minerals (calcium, magnesium, and zinc) that decreases iron
      absorption. METHODS: The population-based prospective cohort of Swedish Men
      (COSM) included 36882 men, aged 45-79 years, who completed a self-administered
      questionnaire on diet and had no history of coronary heart disease, stroke,
      diabetes, or cancer at baseline. RESULTS: During an 11.7 year follow-up, 678
      fatal and 2593 nonfatal AMI events were registered. The hazard ratio (HR) of
      fatal AMI among men in the highest compared with the lowest quintile of heme iron
      intake was 1.51 (95%CI: 1.07-2.13, P-trend=0.02). The association was confined to
      men with a low intake of minerals that can decrease iron absorption. Among men
      with combined intakes of calcium, magnesium, and zinc below the medians, the HR
      of fatal AMI was 2.89 (95%CI: 1.43-5.82) for the highest vs. the lowest quintile
      of heme iron intake. There was no association between heme iron intake and
      nonfatal AMI, or between non-heme iron intake and fatal or nonfatal AMI.
      CONCLUSIONS: Findings from this prospective study indicate that a high heme iron
      intake, particularly with simultaneous low intake of minerals that can decrease
      iron absorption, may increase the risk of fatal AMI.

PMID- 24456872
TI  - Length of stay in hospital is longer in ethnic minority patients after coronary
      artery bypass surgery.

PMID- 24456873
TI  - An extremely rare trigger of Kounis syndrome: Actinidia chinensis.

PMID- 24456874
TI  - Preserved contractile reserve in a dobutamine test for the prediction of a
      response to resynchronisation therapy in ischaemic and non-ischaemic
      cardiomyopathy--a multicenter ViaCRT study.

PMID- 24456875
TI  - Preventive angioplasty in ST-segment elevation myocardial infarction.

PMID- 24456876
TI  - A patient series of dual atrioventricular nodal nonreentrant tachycardia (DAVNNT)
      - an often overlooked diagnosis?

PMID- 24456877
TI  - Complex right ventricular outflow tract ectopy in the absence of organic heart
      disease. Results omicronf a long-term prospective observational study.

PMID- 24456879
TI  - Non-ST segment elevation myocardial infarction due to near-lethal spontaneous
      whole left coronary artery dissection.

PMID- 24456878
TI  - Low admission platelet counts predicts increased risk of in-hospital mortality in
      patients with type A acute aortic dissection.

PMID- 24456880
TI  - Unusual growth of calcium lime with imbrication pattern in human coronary artery.

PMID- 24456881
TI  - Atrial fibrillation-induced cardiac troponin I release.

PMID- 24456882
TI  - Cardiac contractility modulation increases action potential duration dispersion
      and decreases ventricular fibrillation threshold via beta1-adrenoceptor
      activation in the crystalloid perfused normal rabbit heart.
AB  - BACKGROUND/OBJECTIVES: Cardiac contractility modulation (CCM) is a new treatment
      being developed for heart failure (HF) involving application of electrical
      current during the absolute refractory period. We have previously shown that CCM
      increases ventricular force through beta1-adrenoceptor activation in the whole
      heart, a potential pro-arrhythmic mechanism. This study aimed to investigate the
      effect of CCM on ventricular fibrillation susceptibility. METHODS: Experiments
      were conducted in isolated New Zealand white rabbit hearts (2.0-2.5 kg, n=25).
      The effects of CCM (+/- 20 mA, 10 ms phase duration) on the left ventricular
      basal and apical monophasic action potential duration (MAPD) were assessed during
      constant pacing (200 bpm). Ventricular fibrillation threshold (VFT) was defined
      as the minimum current required to induce sustained VF with rapid pacing (30 * 30
      ms). Protocols were repeated during perfusion of the beta1-adrenoceptor
      antagonist metoprolol (1.8 MUM). In separate hearts, the dynamic and spatial
      electrophysiological effects of CCM were assessed using optical mapping with di-4
      ANEPPS. RESULTS: CCM significantly shortened MAPD close to the stimulation site
      (Basal: 102 +/- 5 [CCM] vs. 131 +/- 6 [Control] ms, P<0.001). VFT was reduced
      during CCM (2.6 +/- 0.6 [CCM] vs. 6.1 +/- 0.8 [Control] mA, P<0.01) and was
      correlated (r(2)=0.40, P<0.01) with increased MAPD dispersion (26 +/- 4 [CCM] vs.
      5 +/- 1 [Control] ms, P<0.01) (n=8). Optical mapping revealed greater spread of
      CCM induced MAPD shortening during basal vs. apical stimulation. CCM effects were
      abolished by metoprolol and exogenous acetylcholine. No evidence for direct
      electrotonic modulation of APD was found, with APD adaptation occurring secondary
      to adrenergic stimulation. CONCLUSIONS: CCM decreases VFT in a manner associated
      with increased MAPD dispersion in the crystalloid perfused normal rabbit heart.

PMID- 24456883
TI  - Can autologous bone marrow transplantation improve systolic function in patients
      with multiple myeloma related cardiac amyloidosis?

PMID- 24456884
TI  - Historical note on the attribution of the first description of aortic stenosis in
      the modern era.

PMID- 24456885
TI  - A guide for easy- and difficult-to-treat hypertension.
AB  - Although the blood pressure (BP) of many patients can be controlled using
      standard combinations, treatment of hypertension frequently represents a clinical
      challenge to the primary care physician. This article will review best practices
      for managing patients with easy- and difficult-to-treat hypertension, including
      preferred antihypertensive combinations, optimizing adherence and persistence,
      recognizing white-coat hypertension, and intensifying therapy for treatment
      resistant patients. Each physician must decide based on his or her own level of
      experience at what point a patient becomes too challenging and would benefit from
      referral to a hypertension specialist for more intensive management and to
      complete the exclusion of secondary forms of arterial hypertension. With
      intensive pharmacotherapy, many patients with difficult-to-treat hypertension can
      achieve BP control. If it fails, interventional strategies (e.g., renal
      denervation) are a valid option to get BP controlled. 

PMID- 24456886
TI  - One swallow does not a summer make: safety and renal denervation.
AB  - Renal denervation is increasingly being adopted as a treatment option in patients
      with resistant hypertension. The long-term safety of this procedure is unknown.
      Though the procedure interrupts the sympathetic nerves at the renal level, it
      also has effects on other organ beds, notably the heart and vasculature. These
      effects have been purported to be clinically beneficial and thus formed a
      rationale for examining the role of renal denervation in other conditions,
      including heart failure, arrhythmia, obstructive sleep apnoea and the metabolic
      syndrome. There is a theoretical concern that attenuating the renal sympathetic
      nerves might cause orthostatic hypotension or syncope. From the limited data
      available from hypertension trials, the procedure has not been associated with
      excessive episodes of syncope and this is supported by mechanistic tilt table
      data in asymptomatic patients. Ultimately, the safety of this technique will only
      be established once we have larger phase III/IV studies. 

PMID- 24456887
TI  - Alcohol and the heart: to abstain or not to abstain?

PMID- 24456888
TI  - Secondary amyloidosis in an alkaptonuric aortic valve.

PMID- 24456889
TI  - HDL does not influence the polarization of human monocytes toward an alternative
      phenotype.
AB  - BACKGROUND: Macrophages are crucial cells in the pathogenesis of atherosclerosis.
      Macrophages are plastic cells which can switch from a classical pro-inflammatory
      M1 to an alternative anti-inflammatory M2 macrophage phenotype, depending on the
      environmental stimuli. Because high-density lipoprotein (HDL) cholesterol levels
      are inversely correlated to cardiovascular disease and since HDL displays anti
      inflammatory properties, we investigated whether HDL can affect alternative
      macrophage differentiation of primary human monocytes in the presence of
      interleukin (IL)-4, a M2 macrophage polarization driver, in vitro and ex vivo.
      METHODS AND RESULTS: M2 macrophages are highly responsive to HDL stimulation,
      since the expression of pentraxin 3 (PTX3), a well known HDL target gene, is
      induced by HDL more strongly in M2 macrophages than in control unpolarized
      resting macrophages (RM). As expected, the expression of M2 markers, such as
      Mannose Receptor (MR), CD200 Receptor (CD200R), Coagulation factor XIII A1
      (F13A1), IL-1 receptor antagonist (IL-1RA) and IL10, was induced in IL-4
      polarized M2 macrophages compared to RM. However, incubation with HDL added in
      vitro did not modulate the gene expression of M2 macrophage polarization markers.
      Moreover, monocytes isolated from subjects with genetically low HDL levels,
      carrying ABCA1 or LCAT mutations, differentiated ex vivo into M2 macrophages
      without any difference in the alternative macrophage marker expression profile.
      CONCLUSIONS: These in vitro and ex vivo results indicate that, contrary to mouse
      macrophages, HDL does not influence macrophage M2 polarization of human monocyte
      derived macrophages. Thus, the anti-inflammatory properties of HDL in humans are
      probably not related to the enhancement of the M2 macrophage phenotype.

PMID- 24456890
TI  - Nrf-2-HO-1-HMGB1 axis: an important therapeutic approach for protection against
      myocardial ischemia and reperfusion injury.

PMID- 24456891
TI  - Two dimensional global longitudinal strain of right ventricle using transthoracic
      echocardiography can detect right ventricular fibrosis confirmed by 320 slice CT
      in pulmonary hypertension.

PMID- 24456892
TI  - Clinicopathological features in young patients treated for small-cell lung
      cancer: significance of immunohistological and molecular analyses.
AB  - BACKGROUND: Small-cell lung cancer in young patients is very rare and has not
      been adequately described. In addition, malignancies associated with genetic
      rearrangements of nuclear protein of the testis (NUT) have been reported in young
      patients. PATIENTS AND METHODS: We reviewed the clinical records of patients
      younger than 40 years of age who had been diagnosed as having SCLC and had been
      treated for this condition. We also examined NUT rearrangements using
      immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH)
      analysis. RESULTS: We evaluated the diagnoses and treatment outcomes of 8 young
      patients among 747 SCLC patients. Based on further analyses using IHC staining
      and FISH, NUT rearrangements were found in 2 of these cases. The range of the
      overall survival period was 3.6 to 49.7 months. The 2 patients with NUT
      rearrangements survived for less than 12 months. CONCLUSION: NUT rearrangements
      were identified in 2 patients who had been previously diagnosed as having SCLC.
      Further attention regarding the diagnosis of SCLC in young patients is needed.

PMID- 24456894
TI  - Radiopathological correlations: masses, non-masslike enhancements and MRI-guided
      biopsy.
AB  - MRI-guided biopsy is a recent interventional breast technique. Validating the
      procedure poses a new problem because the signal targeted is created by the
      injection of a paramagnetic contrast agent and is thus transitory. In the first
      instance, the procedure is validated by the radiologist, who checks that
      targeting is accurate and inserts a clip at the end of the procedure, and
      secondly by analysis of the histopathological results, which should be
      representative of the lesion. The pathologist needs to know the nature of the
      image, i.e. whether it is of mass or non-masslike enhancement, and its BI-RADS
      classification. The objective is that the image and the pathological result
      should concur. If the result is non-specific and benign, a follow-up MRI is
      required six months later. 

PMID- 24456893
TI  - Synthetic cationic antimicrobial peptides bind with their hydrophobic parts to
      drug site II of human serum albumin.
AB  - BACKGROUND: Many biologically active compounds bind to plasma transport proteins,
      and this binding can be either advantageous or disadvantageous from a drug design
      perspective. Human serum albumin (HSA) is one of the most important transport
      proteins in the cardiovascular system due to its great binding capacity and high
      physiological concentration. HSA has a preference for accommodating neutral
      lipophilic and acidic drug-like ligands, but is also surprisingly able to bind
      positively charged peptides. Understanding of how short cationic antimicrobial
      peptides interact with human serum albumin is of importance for developing such
      compounds into the clinics. RESULTS: The binding of a selection of short
      synthetic cationic antimicrobial peptides (CAPs) to human albumin with binding
      affinities in the MUM range is described. Competitive isothermal titration
      calorimetry (ITC) and NMR WaterLOGSY experiments mapped the binding site of the
      CAPs to the well-known drug site II within subdomain IIIA of HSA. Thermodynamic
      and structural analysis revealed that the binding is exclusively driven by
      interactions with the hydrophobic moieties of the peptides, and is independent of
      the cationic residues that are vital for antimicrobial activity. Both of the
      hydrophobic moieties comprising the peptides were detected to interact with drug
      site II by NMR saturation transfer difference (STD) group epitope mapping (GEM)
      and INPHARMA experiments. Molecular models of the complexes between the peptides
      and albumin were constructed using docking experiments, and support the binding
      hypothesis and confirm the overall binding affinities of the CAPs. CONCLUSIONS:
      The biophysical and structural characterizations of albumin-peptide complexes
      reported here provide detailed insight into how albumin can bind short cationic
      peptides. The hydrophobic elements of the peptides studied here are responsible
      for the main interaction with HSA. We suggest that albumin binding should be
      taken into careful consideration in antimicrobial peptide studies, as the
      systemic distribution can be significantly affected by HSA interactions.

PMID- 24456895
TI  - Masses in mammography: what are the underlying anatomopathological lesions?
AB  - The semiological description of masses in mammography is based on the BI-RADS
      system provided by the American College of Radiology. The contour is the most
      discriminating morphological criterion between benign and malignant masses. Most
      circumscribed masses are benign. Nevertheless, due to specific histological
      characteristics, certain malignant lesions or lesions with a risk of malignancy
      may appear in the mammography in this falsely reassuring form. An indistinct
      contour in the mammography is suspicious and requires a tissue sample. The
      positive predictive value of malignancy varies according to the morphology of the
      contour. It is lower for microlobulated contours, increases for masked, then
      indistinct contours and reaches 96% for spiculated contours. However, in rare
      cases, certain benign lesions may appear in the form of spiculated masses. In
      these specific cases, a correlation between the histological results with the
      imaging data is essential in order to avoid failing to recognise an underlying
      malignant lesion that the biopsy may have underestimated. 

PMID- 24456897
TI  - Determinants of maximal oxygen uptake (VO2 max) in fire fighter testing.
AB  - The aim of this study was to evaluate current daily practice of aerobic capacity
      testing in Belgian fire fighters. The impact of personal and test-related
      parameters on the outcome has been evaluated. Maximal oxygen uptake (VO2 max)
      results of 605 male fire fighters gathered between 1999 and 2010 were analysed.
      The maximal cardio respiratory exercise tests were performed at 22 different
      centres using different types of tests (tread mill or bicycle), different
      exercise protocols and measuring equipment. Mean VO2 max was 43.3 (SD = 9.8)
      ml/kg.min. Besides waist circumference and age, the type of test, the degree of
      performance of the test and the test centre were statistically significant
      determinants of maximal oxygen uptake. Test-related parameters have to be taken
      into account when interpreting and comparing maximal oxygen uptake tests of fire
      fighters. It highlights the need for standardization of aerobic capacity testing
      in the medical evaluation of fire fighters.

PMID- 24456896
TI  - A comparison of methods currently used in inclusive design.
AB  - Inclusive design has unique challenges because it aims to improve usability for a
      wide range of users. This typically includes people with lower levels of ability,
      as well as mainstream users. This paper examines the effectiveness of two methods
      that are used in inclusive design: user trials and exclusion calculations (an
      inclusive design inspection method). A study examined three autoinjectors using
      both methods (n=30 for the user trials). The usability issues identified by each
      method are compared and the effectiveness of the methods is discussed. The study
      found that each method identified different kinds of issues, all of which are
      important for inclusive design. We therefore conclude that a combination of
      methods should be used in inclusive design rather than relying on a single
      method. Recommendations are also given for how the individual methods can be used
      more effectively in this context. 

PMID- 24456898
TI  - Isolation, purification and characterization of galactomannans as an excipient
      from Senna tora seeds.
AB  - Seed galactomannans are neutral, heterogeneous polysaccharides widely distributed
      in nature. The Mannose/Galactose ratios differ from gum to gum, resulting in a
      change in structure, which in turn, determines the various industrial
      applications of seed galactomannans. Senna tora (Family: Fabaceae) is a fast
      growing and spreading under shrub of which seeds, pods and leaves are extensively
      used for medicinal applications. The seeds have been found to be an alternative
      source of commercial gums. The present investigation deals with isolation,
      purification and characterization of galactomannans from the seeds of Senna tora
      (S. tora). The galactomannan extraction was based on mechanical separation of the
      endosperm, water dissolution, centrifugation and precipitation with acetone. The
      polysaccharide obtained from S. tora seeds was characterized by using
      physicochemical and chromatographic procedures, as well as FTIR, Mass, (13)C NMR
      and (1)H NMR spectroscopy. The results indicated that the gum has the basic
      structure of galactomannans with a main chain of (1->4)-linked beta-D
      mannopyranosyl units to which single alpha-(1->6)-D-linked galactopyranosyl units
      are attached through block pattern. The rheological studies indicated that the S.
      tora gum (1%, w/w) solution possesses pseudoplastic flow. The viscosity and other
      rheological properties confirmed its suitability as an excipient in the
      development of sustained release delivery systems.

PMID- 24456899
TI  - Increased catabolism of nucleic acid in nonalcoholic fatty liver disease patients
      of different ages.
AB  - Uric acid is the end product of nucleic acid catabolism for humanity. Serum uric
      acid level has been suggested to be associated with nonalcoholic fatty liver
      disease (NAFLD). This study aims to examine the association between serum uric
      acid levels and NAFLD in subjects of different ages. A cross-sectional study was
      performed among the patients of different ages with NAFLD (abnormal group) or
      without NAFLD (normal group) in Lianyungang, Jiangsu, China. The levels of serum
      uric acid, total cholesterol, triglyceride, and low density lipoprotein in the
      abnormal group were significantly higher than those in the normal group, while
      the level of high density lipoprotein in the abnormal group was significantly
      lower than that in the normal group (p<0.05). The serum uric acid prevalence,
      total cholesterol, triglyceride, high density lipoprotein, and low density
      lipoprotein in the abnormal group was significantly higher than those in the
      normal group (p<0.05). The serum uric acid, total cholesterol, triglyceride, and
      low density lipoprotein levels and prevalence rates in elderly patients were
      higher than younger and middle aged patients. Serum uric acid level is highly
      associated with NAFLD in patients of different ages. 

PMID- 24456900
TI  - Geo-environmental model for the prediction of potential transmission risk of
      Dirofilaria in an area with dry climate and extensive irrigated crops. The case
      of Spain.
AB  - Zoonotic filarioses caused by Dirofilaria immitis and Dirofilaria repens are
      transmitted by culicid mosquitoes. Therefore Dirofilaria transmission depends on
      climatic factors like temperature and humidity. In spite of the dry climate of
      most of the Spanish territory, there are extensive irrigated crops areas
      providing moist habitats favourable for mosquito breeding. A GIS model to predict
      the risk of Dirofilaria transmission in Spain, based on temperatures and rainfall
      data as well as in the distribution of irrigated crops areas, is constructed. The
      model predicts that potential risk of Dirofilaria transmission exists in all the
      Spanish territory. Highest transmission risk exists in several areas of
      Andalucia, Extremadura, Castilla-La Mancha, Murcia, Valencia, Aragon and
      Cataluna, where moderate/high temperatures coincide with extensive irrigated
      crops. High risk in Balearic Islands and in some points of Canary Islands, is
      also predicted. The lowest risk is predicted in Northern cold and scarcely or non
      irrigated dry Southeastern areas. The existence of irrigations locally increases
      transmission risk in low rainfall areas of the Spanish territory. The model can
      contribute to implement rational preventive therapy guidelines in accordance with
      the transmission characteristics of each local area. Moreover, the use of
      humidity-related factors could be of interest in future predictions to be
      performed in countries with similar environmental characteristics. 

PMID- 24456901
TI  - Synthesis of 5alpha-cholestan-6-one derivatives and their inhibitory activities
      of NO production in activated microglia: discovery of a novel neuroinflammation
      inhibitor.
AB  - Glial activation-mediated neuroinflammation plays a pivotal role in the process
      of several neuroinflammatory diseases including stroke, Alzheimer's diseases,
      Parkinson's diseases, multiple sclerosis and ischemia. Inhibition of microglial
      activation may ameliorate neuronal degeneration under the inflammatory
      conditions. In the present study, a number of 5alpha-cholestan-6-one derivatives
      were prepared and the anti-inflammatory effects of these compounds were evaluated
      in LPS-stimulated BV-2 microglia cells. Those derivatives were synthesized from
      readily available hyodeoxycholic acid (1). Among the tested compounds, several
      analogs (16-18, 25, 35, 38) exhibited potent inhibitory activities on nitric
      oxide production with no or weak cell toxicity. Compound 16 also significantly
      suppressed the expression of TNF-alpha, interleukin (IL)-1beta, cyclooxygenase
      (COX-2) as well as inducible nitric oxide synthase (iNOS) in LPS-stimulated BV-2
      microglia cells. In addition, compound 16 markedly reduced infarction volume in a
      focal ischemic mice model. 

PMID- 24456902
TI  - Synthesis and biological evaluation of novel pazopanib derivatives as antitumor
      agents.
AB  - A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by
      modification of terminal benzene and indazole rings in pazopanib. The structures
      of all the synthesized compounds were confirmed by (1)H NMR and MS. Their
      inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were
      evaluated. All the compounds exhibited definite kinase inhibition, in which
      compound 7l was most potent with IC50 values of 12 nM against VEGFR-2.
      Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity
      against three tyrosine kinases to pazopanib, and compound 7f showed superior
      inhibitory effects than that of pazopanib.

PMID- 24456903
TI  - Activated spinal astrocytes are involved in the maintenance of chronic widespread
      mechanical hyperalgesia after cast immobilization.
AB  - BACKGROUND: In the present study, we examined spinal glial cell activation as a
      central nervous system mechanism of widespread mechanical hyperalgesia in rats
      that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization.
      Activated spinal microglia and astrocytes were investigated immunohistologically
      in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks
      following cast removal. RESULTS: In the lumbar cord, astrocytes were activated
      after microglia. Astrocytes also were activated after microglia in the coccygeal
      cord, but with a delay that was longer than that observed in the lumbar cord.
      This activation pattern paralleled the observation that mechanical hyperalgesia
      occurred in the hindleg or the hindpaw before the tail. The activating
      transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the
      last day of cast immobilization suggested that nerve damage might not occur in
      CPCP rats. The neural activation assessed by the phosphorylated extracellular
      signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast
      removal. In addition, L-alpha-aminoadipate (L-alpha-AA), an inhibitor of
      astrocyte activation administered intrathecally 5 weeks after cast removal,
      inhibited mechanical hyperalgesia in several body parts including the lower leg
      skin and muscles bilaterally, hindpaws, and tail. CONCLUSIONS: These findings
      suggest that activation of lumbar cord astrocytes is an important factor in
      widespread mechanical hyperalgesia in CPCP.

PMID- 24456904
TI  - Smoking- and alcohol habits in relation to the clinical picture of women with
      microscopic colitis compared to controls.
AB  - BACKGROUND: Microscopic colitis (MC) induces gastrointestinal symptoms, which are
      partly overlapping with irritable bowel syndrome (IBS), predominately in middle
      aged and elderly women. The etiology is unknown, but association with smoking has
      been found. The aim of this study was to examine whether the increased risk for
      smokers to develop MC is a true association, or rather the result of confounding
      factors. Therefore, patients suffering from MC and population-based controls from
      the same geographic area were studied regarding smoking- and alcohol habits, and
      other simultaneous, lifestyle factors, concerning the clinical expression of the
      disease. METHODS: Women at the age of 73 years or younger, who had been treated
      for biopsy-verified MC at any of the Departments of Gastroenterology in Skane,
      between 2002 and 2010, were invited to the study (240 patients). Women (737) from
      the population-based prospective cohort study, Malmo Diet and Cancer Study
      (MDCS), served as controls. A self-administered questionnaire about lifestyle
      factors, gastrointestinal symptoms, medical conditions and medication at the time
      for the study was sent by post. RESULTS: Altogether, 131 women with MC could be
      included after age-matching with controls (median age 56 years) and exclusion of
      secondary MC. Patients were divided into persistent MC (MC1) and transient MC
      (MC2). Past smoking was associated with increased risk to develop MC2 (OR = 2.67,
      95 CI = 1.15-6.23), whereas current smoking was associated with increased risk to
      develop MC1 (OR = 3.18, 95 CI = 1.57-6.42). Concomitant symptoms of IBS were
      associated with smoking (OR = 4.24, 95 CI = 1.92-9.32). Alcohol drinking had no
      association with MC or IBS. CONCLUSIONS: The results suggest that past smoking is
      associated with transient MC, whereas current smoking is associated with
      persistent MC. Smoking is associated with MC patients with concomitant IBS-like
      symptoms.

PMID- 24456905
TI  - Disulfide stress: a novel type of oxidative stress in acute pancreatitis.
AB  - Glutathione oxidation and protein glutathionylation are considered hallmarks of
      oxidative stress in cells because they reflect thiol redox status in proteins.
      Our aims were to analyze the redox status of thiols and to identify mixed
      disulfides and targets of redox signaling in pancreas in experimental acute
      pancreatitis as a model of acute inflammation associated with glutathione
      depletion. Glutathione depletion in pancreas in acute pancreatitis is not
      associated with any increase in oxidized glutathione levels or protein
      glutathionylation. Cystine and homocystine levels as well as protein
      cysteinylation and gamma-glutamyl cysteinylation markedly rose in pancreas after
      induction of pancreatitis. Protein cysteinylation was undetectable in pancreas
      under basal conditions. Targets of disulfide stress were identified by Western
      blotting, diagonal electrophoresis, and proteomic methods. Cysteinylated albumin
      was detected. Redox-sensitive PP2A and tyrosine protein phosphatase activities
      diminished in pancreatitis and this loss was abrogated by N-acetylcysteine.
      According to our findings, disulfide stress may be considered a specific type of
      oxidative stress in acute inflammation associated with protein cysteinylation and
      gamma-glutamylcysteinylation and oxidation of the pair cysteine/cystine, but
      without glutathione oxidation or changes in protein glutathionylation. Two types
      of targets of disulfide stress were identified: redox buffers, such as
      ribonuclease inhibitor or albumin, and redox-signaling thiols, which include
      thioredoxin 1, APE1/Ref1, Keap1, tyrosine and serine/threonine phosphatases, and
      protein disulfide isomerase. These targets exhibit great relevance in DNA repair,
      cell proliferation, apoptosis, endoplasmic reticulum stress, and inflammatory
      response. Disulfide stress would be a specific mechanism of redox signaling
      independent of glutathione redox status involved in inflammation. 

PMID- 24456906
TI  - Novel molecular approaches for improving enzymatic and nonenzymatic
      detoxification of 4-hydroxynonenal: toward the discovery of a novel class of
      bioactive compounds.
AB  - 4-Hydroxy-trans-2-nonenal (HNE), an alpha,beta-unsaturated aldehyde generated
      endogenously by the radical-mediated peroxidation of omega-6 polyunsaturated
      fatty acids, is a bioactive molecule acting in several physiopathological
      mechanisms and most of its activity is due to the covalent modification of
      biomolecules. Although at low and physiological levels HNE acts as an endogenous
      signaling molecule, a growing bulk of evidence indicates that at high and toxic
      concentrations, HNE is involved in the onset and propagation of several human
      diseases. To get more conclusive evidence of HNE as a pathogenetic factor, a
      pharmacological tool able to inhibit the HNE-induced cellular response is
      required. Such compound is currently not available, although several molecular
      strategies have so far been reported with the aim of inhibiting HNE formation or
      catalyzing its removal. Although most of these are not selective, such strategies
      have been found to induce several biological responses and would merit further
      investigation. In this review the various strategies are reported and discussed
      together with their limits and potentials. 

PMID- 24456907
TI  - Fast, accurate, and fully automatic segmentation of the right ventricle in short
      axis cardiac MRI.
AB  - This paper presents a fully automatic method to segment the right ventricle (RV)
      from short-axis cardiac MRI. A combination of a novel window-constrained
      accumulator thresholding technique, binary difference of Gaussian (DoG) filters,
      optimal thresholding, and morphology are utilized to drive the segmentation. A
      priori segmentation window constraints are incorporated to guide and refine the
      process, as well as to ensure appropriate area confinement of the segmentation.
      Training and testing were performed using a combined 48 patient datasets supplied
      by the organizers of the MICCAI 2012 right ventricle segmentation challenge,
      allowing for unbiased evaluations and benchmark comparisons. Marked improvements
      in speed and accuracy over the top existing methods are demonstrated. 

PMID- 24456908
TI  - [Current status of thoracoscopic surgery for thoracic and lumbar spine. Part 2:
      treatment of the thoracic disc hernia, spinal deformities, spinal tumors,
      infections and miscellaneous].
AB  - INTRODUCTION: Thoracoscopic surgery or video-assisted thoracic surgery (VATS) of
      the thoracic and lumbar spine has evolved greatly since it appeared less than 20
      years ago. It is currently used in a large number of processes and injuries. The
      aim of this article, in its two parts, is to review the current status of VATS of
      the thoracic and lumbar spine in its entire spectrum. DEVELOPMENT: After
      reviewing the current literature, we developed each of the large groups of
      indications where VATS takes place, one by one. This second part reviews and
      discusses the management, treatment and specific thoracoscopic technique in
      thoracic disc herniation, spinal deformities, tumour pathology, infections of the
      spine and other possible indications for VATS. CONCLUSIONS: Thoracoscopic surgery
      is in many cases an alternative to conventional open surgery. The
      transdiaphragmatic approach has made endoscopic treatment of many thoracolumbar
      junction processes possible, thus widening the spectrum of therapeutic
      indications. These include the treatment of spinal deformities, spinal tumours,
      infections and other pathological processes, as well as the reconstruction of
      injured spinal segments and decompression of the spinal canal if lesion placement
      is favourable to antero-lateral approach. Good clinical results of thoracoscopic
      surgery are supported by growing experience reflected in a large number of
      articles. The degree of complications in thoracoscopic surgery is comparable to
      open surgery, with benefits in regard to morbidity of the approach and subsequent
      patient recovery.

PMID- 24456909
TI  - Lavender oil preparation Silexan is effective in generalized anxiety disorder--a
      randomized, double-blind comparison to placebo and paroxetine.
AB  - The anxiolytic efficacy of the orally administered lavender oil preparation
      Silexan was investigated in generalized anxiety disorder (GAD) in comparison to
      placebo and paroxetine. In this randomized, double-blind, double-dummy trial 539
      adults with GAD according to DSM-5 criteria and a Hamilton Anxiety Scale (HAMA)
      total score ? 18 points participated and received 160 or 80 mg Silexan, 20 mg
      paroxetine, or placebo once daily for 10 wk. The primary efficacy endpoint was
      the HAMA total score reduction between baseline and treatment end. The HAMA total
      score decreased by 14.1 +/- 9.3 points for Silexan 160 mg/d, 12.8 +/- 8.7 points
      for Silexan 80 mg/d, 11.3 +/- 8.0 points for paroxetine, and 9.5 +/- 9.0 points
      for placebo (mean +/- s.d.). Silexan 160 and 80 mg/d were superior to placebo in
      reducing the HAMA total score (p < 0.01) whereas paroxetine showed a trend
      towards significance (p = 0.10) in the full analysis set. The difference between
      paroxetine and placebo was more pronounced in the analysis of observed cases
      (HAMA total score reduction: p < 0.01). In the Silexan 160 mg/d group 73/121
      patients (60.3%) showed a HAMA total score reduction ? 50% of the baseline value
      and 56 (46.3%) had a total score <10 points at treatment end, compared to 70/135
      (51.9%) and 45 (33.3%) for Silexan 80 mg/d, 57/132 (43.2%) and 45 (34.1%) for
      paroxetine, and 51/135 (37.8%) and 40 (29.6%) for placebo. In addition, Silexan
      showed a pronounced antidepressant effect and improved general mental health and
      health-related quality of life. Incidence densities of adverse events (AEs) were
      0.006 AEs/d for Silexan 160 mg/d, 0.008 AEs/d for 80 mg/d, 0.011 AEs/d for
      paroxetine, and 0.008 AEs/d for placebo. In GAD Silexan is more efficacious than
      placebo. AE rates for Silexan were comparable to placebo and lower than for the
      active control paroxetine.

PMID- 24456910
TI  - [Submandibular swelling four years after total thyroidectomy].
AB  - INTRODUCTION: Submandibular swelling most frequently involves the submandibular
      gland. It is often due to lithiasis or to tumor. Some rare cases of submandibular
      swelling have been reported such as submandibular localizations of thyroid
      lesions. Our case study concerns one of these rare occurrences. OBSERVATION: A 47
      year-old female patient consulted for a right-sided submandibular mass
      progressively increasing in size during the previous 2 years. The patient had
      undergone a total thyroidectomy, 4 years before consulting, for a toxic
      multinodular goiter THAT had been treated by L-thyroxin replacement therapy per
      os since the surgery. TSH and LT4 levels were normal. A CT scan revealed a large
      tumor in the right submandibular space with heterogeneous contrast. Fine needle
      cytopuncture allowed observing follicular cellules suggesting thyroid origin. The
      cervicotomy confirmed the diagnosis of an ectopic goiter. DISCUSSION: Thyroid
      disorders may in rare cases concern the submandibular space. A history of thyroid
      disorders should be taken into account for the etiological diagnosis of unusual
      submandibular masses in maxillo-facial surgery.

PMID- 24456911
TI  - [Myoepithelial carcinoma of the lacrimal gland].
AB  - INTRODUCTION: Myoepithelial carcinomas are unusual tumors most often located in
      salivary glands. It is very rarely located in lacrimal glands; only 5 cases have
      been reported. We report a sixth case. OBSERVATION: An 88-year-old male patient
      presented with diplopia, painless right sided exophthalmia, as well as eyeball
      deviation due to a tumor located at upper external quadrant of the orbit. A
      biopsy initially suggested a sarcoma. The pathological analysis of the biopsy
      allowed diagnosing a myoepithelial carcinoma of the lacrimal gland. Despite the
      monoblock resection of the tumor, a recurrence was observed 3 months after
      removal. The patient died 8 months after the initial surgery. DISCUSSION: This
      case illustrates the clinical and pathological characteristics of a myoepithelial
      carcinoma. This tumor has a high grade of malignancy, and is very rarely
      described in lacrimal glands. The morphological diagnosis of this tumor is
      difficult with a problematic differential diagnosis with fusiform cells sarcomas
      (leiomyosarcoma, undifferentiated sarcoma), and epithelial-myoepithelial
      carcinoma.

PMID- 24456912
TI  - [Etiologic diagnosis of jaw osteonecrosis, other than bisphosphonate and
      radiotherapy related osteitis].
AB  - Our purpose was to highlight the various etiologies of maxillo-mandibular
      osteonecrosis, other than radiotherapy and biphosphonate related osteitis that
      have been abundantly reported. We performed a PubMed search from August 1, 1972
      to August 1, 2012 using the following MeSH terms: "osteonecrosis", "bone",
      "necrosis", "jaw", "maxilla", "mandible", "palate", "oral", "avascular necrosis",
      NOT "bisphosphonate" NOT "osteoradionecrosis". Most cases of osteonecrosis were
      iatrogenic. Viral, mycotic, or bacterial infections were less frequent causes.
      Cocaine abuse, Wegener's granulomatosis, and N/K lymphoma were other etiologies.
      It is important to identify the various etiologies rapidly to manage this
      sometimes very mutilating condition adequately. 

PMID- 24456913
TI  - Etiologic diagnosis of jaw osteonecrosis, other than bisphosphonate and
      radiotherapy related osteonecrosis.
AB  - Our purpose was to highlight the various etiologies of maxillo-mandibular
      osteonecrosis, other than radiotherapy and biphosphonate related osteitis that
      have been abundantly reported. We performed a PubMed search from August 1, 1972
      to August 1, 2012 using the following MeSH terms: "osteonecrosis", "bone",
      "necrosis", "jaw", "maxilla", "mandible", "palate", "oral", "avascular necrosis",
      NOT "bisphosphonate" NOT "osteoradionecrosis". Most cases of osteonecrosis were
      iatrogenic. Viral, mycotic, or bacterial infections were less frequent causes.
      Cocaine abuse, Wegener's granulomatosis, and N/K lymphoma were other etiologies.
      It is important to identify the various etiologies rapidly to manage this
      sometimes very mutilating condition adequately. 

PMID- 24456914
TI  - [Desmoplastic fibroma of the zygoma].
AB  - INTRODUCTION: Desmoplastic fibroma is a benign and rare intraosseous tumor. This
      lesion is locally aggressive and has a high tendency to recur. OBSERVATION: The
      authors report the diagnostic and therapeutic management of a 26-year-old female
      patient who presented with a desmoplastic fibroma of the zygoma. DISCUSSION: This
      localization is extremely rare and only 2 cases have been reported. The clinical
      and radiological signs are pauci-specific. The diagnosis is most often
      established according to anatomopathology and immunohistochemistry results. The
      recommended management is extensive surgical resection.

PMID- 24456915
TI  - [50th SFSCMFCO congress in Lyon: continuing professional development (CPD)
      program].

PMID- 24456916
TI  - [The French Society of Stomatology and Maxillofacial and Oral Surgery in 2014].

PMID- 24456917
TI  - Foot orientation affects muscle activation levels of ankle stabilizers in a
      single-legged balance board protocol.
AB  - CONTEXT: The main goal of balance training is regaining a normal neuromuscular
      control to a functional level. Although uniaxial balance boards are commonly
      used, no research has been done on the effect of foot orientation on muscle
      activation levels. OBJECTIVE: To investigate the effect of foot orientation on
      muscle activation levels and modulation of the ankle stabilizing muscles in a
      single-legged balance protocol on a uniaxial balance board. METHODS: Sixty-nine
      healthy subjects (age: 21.8+/-1.7years; mass: 67.5+/-11.9kg; body height: 174.7+/
      8.6cm; BMI: 21.5+/-3.0) participated in this study. Subjects were asked to keep
      their balance during a single leg stance on a uniaxial balance board for four
      different foot orientations, aligning the board's rotation axis with frontal,
      sagittal, diagonal and subtalar axes of the foot, respectively. Surface
      electromyography registered muscle activity of peroneus longus, tibialis
      anterior, medial and lateral gastrocnemius muscles. RESULTS: Highest muscle
      activation levels and modulation for the peroneus longus were registered
      exercising along the frontal axis; for the tibialis anterior along the diagonal
      axis; for the medial gastrocnemius along the sagittal axis; and for the lateral
      gastrocnemius along the diagonal axis. CONCLUSION: Foot orientation modifications
      on a uniaxial balance board allows to differentially target specific ankle
      stabilizing muscles during balance training.

PMID- 24456918
TI  - [Are useful the diabetic foot units?].

PMID- 24456919
TI  - [Pneumatosis intestinalis].

PMID- 24456920
TI  - [Actinomyces meyeri brain abscess].

PMID- 24456921
TI  - [Role of corticosteroids in peripheral neuropathy of chronic obstructive
      pulmonary disease patients].

PMID- 24456922
TI  - [Liraglutide in polycystic ovary syndrome].

PMID- 24456923
TI  - [Genetic polymorphisms and lung cancer risk].

PMID- 24456924
TI  - [Evolution of the liver graft from a asystole donor].

PMID- 24456926
TI  - Ontogeny of the immune system in Acipenserid juveniles.
AB  - Sturgeon aquaculture has increased considerably worldwide but little is known
      about their immunological development and competence in early life stages.
      Culture of larvae is one of the most critical stages in intensive sturgeon
      farming, often associated with high mortality rates. The objective of this study
      was to characterize the developmental morphology (light and transmission electron
      microscopy, LM and TEM) of the meningeal myeloid tissue, spleen and thymus in
      Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus) from hatching until 5 months
      old (2895 degrees C.day (dd)). The spleen was first visible on 541 dd larvae LM
      sections and the other two immune organs in 768 dd samples (approximately 400 and
      600 dd after onset of feeding). Generally, younger fish had significantly higher
      percentages of undifferentiated cells (meningeal myeloid tissue and spleen) and
      effective adaptive immune competence would not be expected in these fish on the
      onset of feeding, but further functional immune assessment is needed.

PMID- 24456927
TI  - Combined analysis of chromosomal instabilities and gene expression for colon
      cancer progression inference.
AB  - BACKGROUND: Copy number alterations (CNAs) represent an important component of
      genetic variations. Such alterations are related with certain type of cancer
      including those of the pancreas, colon, and breast, among others. CNAs have been
      used as biomarkers for cancer prognosis in multiple studies, but few works report
      on the relation of CNAs with the disease progression. Moreover, most studies do
      not consider the following two important issues. (I) The identification of CNAs
      in genes which are responsible for expression regulation is fundamental in order
      to define genetic events leading to malignant transformation and progression.
      (II) Most real domains are best described by structured data where instances of
      multiple types are related to each other in complex ways. RESULTS: Our main
      interest is to check whether the colorectal cancer (CRC) progression inference
      benefits when considering both (I) the expression levels of genes with CNAs, and
      (II) relationships (i.e. dissimilarities) between patients due to expression
      level differences of the altered genes. We first evaluate the accuracy
      performance of a state-of-the-art inference method (support vector machine) when
      subjects are represented only through sets of available attribute values (i.e.
      gene expression level). Then we check whether the inference accuracy improves,
      when explicitly exploiting the information mentioned above. Our results suggest
      that the CRC progression inference improves when the combined data (i.e. CNA and
      expression level) and the considered dissimilarity measures are applied.
      CONCLUSIONS: Through our approach, classification is intuitively appealing and
      can be conveniently obtained in the resulting dissimilarity spaces. Different
      public datasets from Gene Expression Omnibus (GEO) were used to validate the
      results.

PMID- 24456928
TI  - The trials methodological research agenda: results from a priority setting
      exercise.
AB  - BACKGROUND: Research into the methods used in the design, conduct, analysis, and
      reporting of clinical trials is essential to ensure that effective methods are
      available and that clinical decisions made using results from trials are based on
      the best available evidence, which is reliable and robust. METHODS: An on-line
      Delphi survey of 48 UK Clinical Research Collaboration registered Clinical Trials
      Units (CTUs) was undertaken. During round one, CTU Directors were asked to
      identify important topics that require methodological research. During round two,
      their opinion about the level of importance of each topic was recorded, and
      during round three, they were asked to review the group's average opinion and
      revise their previous opinion if appropriate. Direct reminders were sent to
      maximise the number of responses at each round. Results are summarised using
      descriptive methods. RESULTS: Forty one (85%) CTU Directors responded to at least
      one round of the Delphi process: 25 (52%) responded in round one, 32 (67%)
      responded in round two, 24 (50%) responded in round three. There were only 12
      (25%) who responded to all three rounds and 18 (38%) who responded to both rounds
      two and three. Consensus was achieved amongst CTU Directors that the top three
      priorities for trials methodological research were 'Research into methods to
      boost recruitment in trials' (considered the highest priority), 'Methods to
      minimise attrition' and 'Choosing appropriate outcomes to measure'. Fifty other
      topics were included in the list of priorities and consensus was reached that two
      topics, 'Radiotherapy study designs' and 'Low carbon trials', were not
      priorities. CONCLUSIONS: This priority setting exercise has identified the
      research topics felt to be most important to the key stakeholder group of
      Directors of UKCRC registered CTUs. The use of robust methodology to identify
      these priorities will help ensure that this work informs the trials
      methodological research agenda, with a focus on topics that will have most impact
      and relevance.

PMID- 24456929
TI  - NLRP3 promotes autophagy of urate crystals phagocytized by human osteoblasts.
AB  - INTRODUCTION: Monosodium urate (MSU) microcrystals present in bone tissues of
      chronic gout can be ingested by nonprofessional phagocytes like osteoblasts (OBs)
      that express NLRP3 (nucleotide-binding domain and leucine-rich repeat region
      containing family of receptor protein 3). MSU is known to activate NLRP3
      inflammasomes in professional phagocytes. We have identified a new role for NLRP3
      coupled to autophagy in MSU-stimulated human OBs. METHODS: Normal human OBs
      cultured in vitro were investigated for their capacity for phagocytosis of MSU
      microcrystals by using confocal microscopy. Subsequent mineralization and matrix
      metalloproteinase activity were evaluated, whereas regulatory events of
      phagocytosis were deciphered by using signaling inhibitors, phosphokinase arrays,
      and small interfering RNAs. Statistics were carried out by using paired or
      unpaired t tests, and the one-way ANOVA, followed by multiple comparison test.
      RESULTS: Most of the OBs internalized MSU in vacuoles. This process depends on
      signaling via PI3K, protein kinase C (PKC), and spleen tyrosine kinase (Syk), but
      is independent of Src kinases. Simultaneously, MSU decreases phosphorylation of
      the protein kinases TOR (target of rapamycin) and p70S6K. MSU activates the
      cleavage of microtubule-associated protein light chain 3 (LC3)-I into LC3-II, and
      MSU microcrystals are coated with GFP-tagged LC3. However, MSU-stimulated
      autophagy in OBs absolutely requires the phagocytosis process. We find that MSU
      upregulates NLRP3, which positively controls the formation of MSU-autophagosomes
      in OBs. MSU does not increase death and late apoptosis of OBs, but reduces their
      proliferation in parallel to decreasing their competence for mineralization and
      to increasing their matrix metalloproteinase activity. CONCLUSIONS: MSU
      microcrystals, found locally encrusted in the bone matrix of chronic gout,
      activate phagocytosis and NLRP3-dependent autophagy in OBs, but remain intact in
      permanent autophagosomes while deregulating OB functions.

PMID- 24456930
TI  - Reproductive factors, intima media thickness and carotid plaques in a cross
      sectional study of postmenopausal women enrolled in the population-based KORA F4
      study.
AB  - BACKGROUND: Reproductive events may affect the onset of chronic diseases. We
      examined the possible association between reproductive parameters and intima
      media thickness (IMT) or carotid plaques in the common carotid artery in a
      population-based sample. METHODS: This cross-sectional study analysed data of 800
      postmenopausal women aged 50 to 81 years of the population-based KORA F4 study,
      conducted between 2006 and 2008 in Southern Germany. Reproductive parameters were
      obtained by standardised interviews. RESULTS: Age at menarche below 12 years
      compared to 12-15 years was significantly associated with carotid plaques (age
      adjusted OR 2.23, 95% CI 1.13-4.43, p-value 0.018, multivariable adjusted 2.11,
      1.05-4.26, 0.037), but not with IMT. Ever use of hormone replacement therapy was
      inversely associated with carotid plaques (age-adjusted 0.60, 0.44-0.81, p =
      0.001, multivariable-adjusted 0.62, 0.45-0.86, 0.003) and IMT in the age-adjusted
      model (mean 0.89, 95% CI 0.88-0.90, p = 0.033) but not in the multivariable
      adjusted model (mean 0.89, 95% CI 0.88-0.90, p = 0.075). Parity, age at
      menopause, time since menopause, duration of fertile period, current use of
      hormone replacement therapy, ever use of oral contraceptives, hysterectomy,
      bilateral oophorectomy, hot flashes and depressive mood in relation to the
      menopausal transition were not associated with carotid plaques or IMT.
      CONCLUSION: Our study showed, that there may be an independent association
      between the reproductive parameters age at menarche and ever use of hormone
      replacement therapy with carotid plaques in the common carotid artery, but not
      with IMT. Further research, especially in studies with prospective population
      based study design, is necessary to assess in detail what events in women's life
      lead to increased IMT or CP.

PMID- 24456931
TI  - Mitogenome sequence variation in migratory and stationary ecotypes of North-east
      Atlantic cod.
AB  - Sequencing of mitochondrial gene fragments from specimens representing a wide
      range of geographical locations has indicated limited population structuring in
      Atlantic cod (Gadus morhua). We recently performed whole genome analysis based on
      next-generation sequencing of two pooled ecotype samples representing offshore
      migratory and inshore stationary cod from the North-east Atlantic Ocean. Here we
      report molecular features and variability of the 16.7kb mitogenome component that
      was collected from the datasets. These sequences represented more than 25 times
      coverage of each individual and more than 1100 times coverage of each ecotype
      sample. We estimated the mitogenome to have evolved 14 times more rapidly than
      the nuclear genome. Among the 365 single nucleotide polymorphism (SNP) sites
      identified, 121 were shared between ecotypes, and 151 and 93 were private within
      the migratory and stationary cod, respectively. We found 323 SNPs to be located
      in protein coding genes, of which 29 were non-synonymous. One synonymous site in
      ND2 was likely to be under positive selection. FST measurements indicated weak
      differentiation in ND1 and ND2 between ecotypes. We conclude that the Atlantic
      cod mitogenome and the nuclear genome apparently evolved by distinct evolutionary
      constraints, and that the reproductive isolation observed from whole genome
      analysis was not visible in the mtDNA sequences. 

PMID- 24456933
TI  - Enhanced intestinal permeability and oral bioavailability of enalapril maleate
      upon complexation with the cationic polymethacrylate Eudragit E100.
AB  - The low bioavailability of enalapril maleate associated to its instability in
      solid state motivated the development of a polyelectrolyte-drug complex between
      enalapril maleate and the cationic polymethacrylate Eudragit E100. The solid
      complexes were characterized by DSC-TG, FT-IR and X-ray diffraction. Their
      aqueous dispersions were evaluated for drug delivery in bicompartimental Franz
      cells and electrokinetic potentials. Stability in solid state was also evaluated
      using an HPLC-UV stability indicating method. Absorption of enalapril maleate was
      assessed thorough the rat everted gut sac model. In addition, urinary recovery
      after oral administration in rats was used as an indicator of systemic
      exposition. The solid materials are stable amorphous solids in which both
      moieties of enalapril maleate are ionically bonded to the polymer. Their aqueous
      dispersions exhibited controlled release over more than 7h in physiologic saline
      solution, being ionic exchange the fundamental mechanism that modified the extent
      and rate of drug release. Intestinal permeation of enalapril maleate was 1.7
      times higher in the presence of the cationic polymer. This increase can be
      related with the capacity to adhere the mucosa due to the positive zeta potential
      of the complexes. As a consequence bioavailability was significantly improved
      (1.39 times) after oral administration of the complexes. In addition, no signs of
      chemical decomposition were observed after a 14months period. The results
      indicated that the products are new chemical entities that improve unfavorable
      properties of a useful drug. 

PMID- 24456934
TI  - Diagnosis and classification of drug-induced autoimmunity (DIA).
AB  - Since sulfadiazine associated lupus-like symptoms were first described in 1945,
      certain drugs have been reported to interfere with the immune system and induce a
      series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified
      by systemic lupus erythematosus (SLE). Among the drugs, procainamide and
      hydralazine are considered to be associated with the highest risk for developing
      lupus, while quinidine has a moderate risk, and all other drugs have low or very
      low risk. More recently, drug-induced lupus has been associated with the use of
      newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors
      and cytokines. In addition to lupus, other major autoimmune diseases, including
      vasculitis and arthritis, have also been associated with drugs. Because
      resolution of symptoms generally occurs after cessation of the offending drugs,
      early diagnosis is crucial for treatment strategy and improvement of prognosis.
      Unfortunately, it is difficult to establish standardized criteria for DIA
      diagnosis. Diagnosis of DIA requires identification of a temporal relationship
      between drug administration and the onset of symptoms, but the relative risk with
      respect to dose and duration for each drug has rarely been determined. DIA is
      affected by multiple genetic and environmental factors, leading to difficulties
      in establishing a list of global clinical features that are characteristic of
      most or all DIA patients. Moreover, the distinction between authentic DIA and
      unmasking of a latent autoimmune disease also poses challenges. In this review,
      we summarize the highly variable clinical features and laboratory findings of
      DIA, with an emphasis on the diagnostic criteria. 

PMID- 24456935
TI  - Classification criteria of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a chronic, systemic autoimmune disease that affects
      typically the exocrine glands causing mucosal dryness. Dry eyes and mouth are
      considered by far the most common and early symptoms of the disease but systemic
      complications may also occur. In 1993, the preliminary European criteria were
      proposed and widely accepted, consisting of both subjective and objective
      criteria. Almost ten years later, these classification criteria were revised by
      introducing more stringent rules and precise diagnostic procedures leading to the
      currently used American-European Consensus Group (AECG) criteria. The AECG
      criteria have been largely employed to conduct epidemiologic and clinical studies
      of patients with SS and proved to be more specific compared to the preliminary
      European criteria. The recent American College of Rheumatology/Sjogren's
      International Collaborative Clinical Alliance (ACR/SICCA) criteria that are based
      exclusively on objective tests, the stringency of the AECG criteria and the
      potential therapeutic use of biologic agents in SS clearly set the need for new
      classification criteria. Whether the new diagnostic approach will further
      encompass subclinical and early forms of the disease remains to be addressed by
      the scientific community. 

PMID- 24456936
TI  - Diagnosis and classification of Goodpasture's disease (anti-GBM).
AB  - Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM
      disease) is included among immune complex small vessel vasculitides. The
      definition of anti-GBM disease is a vasculitis affecting glomerular capillaries,
      pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies.
      The disease is a prototype of autoimmune disease, where the patients develop
      autoantibodies that bind to the basement membranes and activate the classical
      pathway of the complement system, which start a neutrophil dependent
      inflammation. The diagnosis of anti-GBM disease relies on the detection of anti
      GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt
      clinical symptoms are most prominent in the glomeruli where the inflammation
      usually results in a severe rapidly progressive glomerulonephritis. Despite
      modern treatment less than one third of the patients survive with a preserved
      kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases
      per million inhabitants per year and there is a strong genetic linkage to HLA
      DRB1(*)1501 and DRB1(*)1502. Essentially, anti-GBM disease is now a preferred
      term for what was earlier called Goodpasture's syndrome or Goodpasture's disease;
      anti-GBM disease is now classified as small vessel vasculitis caused by in situ
      immune complex formation; the diagnosis relies on the detection of anti-GBM in
      tissues or circulation in conjunction with alveolar or glomerular disease;
      therapy is effective only when detected at an early stage, making a high degree
      of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO
      ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test
      for ANCA is ordered in patients with renal disease. 

PMID- 24456937
TI  - [Inhibition of lactation: end to the bromocriptin, long life to the
      carbergolin?].

PMID- 24456932
TI  - Approach to the diagnosis of congenital myopathies.
AB  - Over the past decade there have been major advances in defining the genetic basis
      of the majority of congenital myopathy subtypes. However the relationship between
      each congenital myopathy, defined on histological grounds, and the genetic cause
      is complex. Many of the congenital myopathies are due to mutations in more than
      one gene, and mutations in the same gene can cause different muscle pathologies.
      The International Standard of Care Committee for Congenital Myopathies performed
      a literature review and consulted a group of experts in the field to develop a
      summary of (1) the key features common to all forms of congenital myopathy and
      (2) the specific features that help to discriminate between the different genetic
      subtypes. The consensus statement was refined by two rounds of on-line survey,
      and a three-day workshop. This consensus statement provides guidelines to the
      physician assessing the infant or child with hypotonia and weakness. We summarise
      the clinical features that are most suggestive of a congenital myopathy, the
      major differential diagnoses and the features on clinical examination,
      investigations, muscle pathology and muscle imaging that are suggestive of a
      specific genetic diagnosis to assist in prioritisation of genetic testing of
      known genes. As next generation sequencing becomes increasingly used as a
      diagnostic tool in clinical practise, these guidelines will assist in determining
      which sequence variations are likely to be pathogenic. 

PMID- 24456938
TI  - [How I do...an abdominoperineal resection with a Taylor flap reconstruction for
      vulvar carcinoma].

PMID- 24456940
TI  - De novo duplication of chromosome 16p in a female infant with signs of neonatal
      hemochromatosis.
AB  - Reported cases of "pure" duplication of the entire short arm of chromosome 16
      (16p) are rare, with only 7 patients described in the literature. We report on a
      female infant with de novo 16p duplication localized to the short arm of
      chromosome 6, detected by chromosomal analysis and characterized by array CGH and
      fluorescence in situ hybridization. This baby girl presented with clinical
      symptoms characteristic of patients with duplications of the short arm of
      chromosome 16: psychomotor retardation, constitutional growth delay and specific
      dysmorphic features, including proximally placed hypoplastic thumbs. In addition,
      she exhibited evidence of neonatal hemochromatosis as shown by direct
      hyperbilirubinemia, iron overload and elevated liver enzyme levels. To our
      knowledge, this is the first report of signs of neonatal hemochromatosis in a
      patient with 16p duplication. 

PMID- 24456941
TI  - Female mice liberated for inclusion in neuroscience and biomedical research.
AB  - The underrepresentation of female mice in neuroscience and biomedical research is
      based on the assumption that females are intrinsically more variable than males
      and must be tested at each of four stages of the estrous cycle to generate
      reliable data. Neither belief is empirically based. In a meta-analysis of 293
      articles, behavioral, morphological, physiological, and molecular traits were
      monitored in male mice and females tested without regard to estrous cycle stage;
      variability was not significantly greater in females than males for any endpoint
      and was substantially greater in males for several traits. Group housing of mice
      increased variability in both males and females by 37%. Utilization of female
      mice in neuroscience research does not require monitoring of the estrous cycle.
      The prevalence of sex differences at all levels of biological organization, and
      limitations in generalizing findings obtained with males to females, argue for
      the routine inclusion of female rodents in most research protocols. 

PMID- 24456939
TI  - Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel
      cancer markers.
AB  - Carcinoma of the stomach is one of the most prevalent cancer types in the world.
      Although the incidence of gastric cancer is declining, the outcomes of gastric
      cancer patients remain dismal because of the lack of effective biomarkers to
      detect early gastric cancer. Modern biomedical research has explored many
      potential gastric cancer biomarker genes by utilising serum protein antigens,
      oncogenic genes or gene families through improving molecular biological
      technologies, such as microarray, RNA-Seq and the like. Recently, the small
      noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the
      oncogenesis pathways and to serve as useful clinical biomarkers. This new class
      of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis,
      including gastric cancer. By translational suppression of target genes, miRNAs
      play a significant role in the gastric cancer cell physiology and tumour
      progression. There are potential implications of previously discovered gastric
      cancer molecular biomarkers and their expression modulations by respective
      miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour
      suppressing functions in human cancers. With the surprising stability of miRNAs
      in tissues, serum or other body fluids, miRNAs have emerged as a new type of
      cancer biomarker with immeasurable clinical potential. 

PMID- 24456942
TI  - Genetics of borderline personality disorder: systematic review and proposal of an
      integrative model.
AB  - Borderline personality disorder (BPD) is one of the most common mental disorders
      and is characterized by a pervasive pattern of emotional lability, impulsivity,
      interpersonal difficulties, identity disturbances, and disturbed cognition. Here,
      we performed a systematic review of the literature concerning the genetics of
      BPD, including familial and twin studies, association studies, and gene
      environment interaction studies. Moreover, meta-analyses were performed when at
      least two case-control studies testing the same polymorphism were available. For
      each gene variant, a pooled odds ratio (OR) was calculated using fixed or random
      effects models. Familial and twin studies largely support the potential role of a
      genetic vulnerability at the root of BPD, with an estimated heritability of
      approximately 40%. Moreover, there is evidence for both gene-environment
      interactions and correlations. However, association studies for BPD are sparse,
      making it difficult to draw clear conclusions. According to our meta-analysis, no
      significant associations were found for the serotonin transporter gene, the
      tryptophan hydroxylase 1 gene, or the serotonin 1B receptor gene. We hypothesize
      that such a discrepancy (negative association studies but high heritability of
      the disorder) could be understandable through a paradigm shift, in which
      "plasticity" genes (rather than "vulnerability" genes) would be involved. Such a
      framework postulates a balance between positive and negative events, which
      interact with plasticity genes in the genesis of BPD. 

PMID- 24456943
TI  - Skeletal muscle's 3rd year anniversary.

PMID- 24456944
TI  - Peroxisome proliferator activated receptor gamma (PPARgamma) as a therapeutic
      target for improvement of cognitive performance in Fragile-X.
AB  - Rare disorders leading to intellectual disability, such as Fragile X syndrome
      (FXS) alter synaptic plasticity. Ligand identification of orphan nuclear
      receptors has led to the discovery of many signaling pathways and has revealed a
      direct link of nuclear receptors with human conditions such as mental retardation
      and neurodegenerative diseases. PPARgamma agonists can act as neuroprotective
      agents, promoting synaptic plasticity and neurite outgrowth. Therefore, selective
      PPARgamma agonists are good candidates for therapeutic evaluation in intellectual
      disabilities. Preliminary results suggest that PPARgamma agonists such as
      Pioglitazone, Rosiglitazone and synthetic agonist, GW1929, are used as the
      therapeutic agent in neurological disorders. These components interact with
      intracellular transduction signals (e.g. GSK3beta, PI3K/Akt, Wnt/beta-Catenin,
      Rac1 and MMP-9). It seems that interaction with these pathways can improve memory
      recognition in FXS animal models. The present hypothesis consists of enhancing
      synaptic plasticity that may then rescue the learning and memory in FXS. This
      will open many new therapeutic avenues for a variety of human diseases. 

PMID- 24456945
TI  - Anakinra-responsive lichen planus in a woman with Erdheim-Chester disease: a
      therapeutic enigma.
AB  - BACKGROUND: Anakinra is a recombinant form of interleukin-1 receptor antagonist.
      It is the drug of choice for Schnitzler syndrome and cryopyrin-associated
      periodic syndromes. It has also recently been demonstrated to have activity in
      the treatment of the non-Langerhans cell histiocytosis known as Erdheim-Chester
      disease. PURPOSE: To describe the activity of anakinra in a patient with co
      existing lichen planus and Erdheim-Chester disease. METHODS: A 43-year-old woman
      with progressive Erdheim-Chester disease presented for management of her night
      sweats and chills, systemic skeletal bone pain, and neurologic (diabetes
      insipidus) manifestations. She also had widespread cutaneous lichen planus.
      Anakinra, 100 mg subcutaneously daily, was initiated for the treatment of her
      Erdheim-Chester disease. RESULTS: Within 2 days of starting anakinra, there was
      prompt resolution of her Erdheim-Chester disease-related symptoms. Subsequently,
      her bone pain resolved and her diabetes insipidus improved. Also, the lichen
      planus-associated pruritus rapidly ceased and most of the skin lesions improved.
      CONCLUSIONS: Our experience confirms the efficacy of anakinra for the treatment
      of Erdheim-Chester disease. The concomitant improvement of her lichen planus on
      anakinra suggests that this agent warrants additional study in this disorder.

PMID- 24456946
TI  - Imatinib-induced postoperative periorbital purpura: GASP (Gleevec-Associated
      Surgical Purpura) in a woman with imatinib-treated chronic myelogenous leukemia.
AB  - BACKGROUND: Imatinib mesylate is a selective tyrosine kinase inhibitor used in
      the treatment of chronic myelogenous leukemia. Ocular side effects of imatinib
      include periorbital edema, which may become so severe as to obstruct the visual
      field. PURPOSE: The purpose of this case study is to describe the clinical
      characteristics of imatinib- induced postoperative periorbital purpura. MATERIALS
      AND METHODS: We retrospectively reviewed the medical literature using PubMed,
      searching the terms edema, Gleevec, imatinib, periorbital, postoperative and
      purpura. Patient reports and previous reviews of the subject were critically
      assessed and the salient features are presented. RESULTS: Three patients have
      undergone surgery to reduce the imatinib-induced periorbital edema; two of these
      individuals have developed imatinib-induced postoperative periorbital purpura.
      CONCLUSION: We recommend discontinuing imatinib usage one week prior to
      periorbital surgery and not resuming therapy until the eighth postoperative day.

PMID- 24456947
TI  - Increasing recognition of dermatomyositis with subcutaneous edema - is this a
      poorer prognostic marker?
AB  - Subcutaneous edema as a presenting feature of dermatomyositis has infrequently
      been described and is thought to signify a more aggressive disease course. We
      report a case involving a 38-year-old man who presented with significant
      subcutaneous edema involving his neck and upper body; he later developed clinical
      features and biopsy results consistent with dermatomyositis. Only sixteen
      previous cases of dermatomyositis with subcutaneous edema involving adults have
      been published in the literature and we aim to review disease progression,
      prognosis, and optimal treatment of the condition. 

PMID- 24456948
TI  - Alpha-1-antitrypsin deficiency-associated panniculitis: a case report.
AB  - Panniculitis is a recognized, but rare complication of alpha1-antitrypsin (A1AT)
      deficiency. Less than 60 cases have been reported, mostly in the homozygous PiZZ
      variant. We report the case of a 55-year old woman with A1AT panniculitis
      associated with the heterozygous phenotype PiMS and discrete reduction of A1AT
      serum levels. In addition, the pathophysiology of the disease, clinical and
      histopathological features, and current treatment possibilities are briefly
      reviewed. 

PMID- 24456949
TI  - Eruptive purpuric papules on the arms; a case of chemotherapy-induced
      inflammation of actinic keratoses and review of the literature.
AB  - Chemotherapy-induced inflammation of actinic keratosis can present in patients
      with subclinical actinic keratoses that become erythematous and pruritic within
      weeks of initiating systemic chemotherapy. The reaction is limited to sun-exposed
      areas and, classically, histologic findings of parakeratosis and epidermal
      necrosis with keratinocyte nuclear pleomorphism are present. Exuberant reactions
      with extensive epidermal necrosis may lead to subepidermal vesiculation. We
      report a case of a 67-year-old man with a history of chronic hepatitis B virus
      infection and recently diagnosed squamous cell carcinoma of the lung who was
      noted to have progressive asymptomatic violaceous papules on the extensor
      forearms and distal upper arms while hospitalized for possible sepsis following
      initiation of chemotherapy. A dermatology consulatation was requested to rule out
      possible vasculitis. It is important to recognize chemotherapy-induced
      inflammation of actinic keratoses in predisposed patients; it may be managed
      successfully with topical corticosteroids and does not necessitate
      discontinuation of the offending chemotherapeutic agent. 

PMID- 24456950
TI  - Primary amyloidosis-induced nail dystrophy.
AB  - Primary amyloidosis is caused by a monoclonal proliferation of plasma cells and
      is capable of producing cutaneous lesions. A 56-year-old male was admitted to the
      hospital for evaluation of chronic back pain and acute lower extremity weakness.
      On examination, he was noted to have subungual verrucous plaques with overlying
      nail dystrophy on his bilateral thumbs. A biopsy of one subungual lesion showed a
      deposition of amorphous material in the dermis that stained with Congo red and
      crystal violet. These cutaneous lesions ultimately led to the diagnosis of plasma
      cell dyscrasia and primary amyloidosis. Based on the literature search, primary
      amyloidosis presenting with this degree of subungual thickening and overlying
      nail dystrophy has not been previously reported. 

PMID- 24456951
TI  - Systematized linear epidermolytic hyperkeratosis.
AB  - A 5-year-old boy presented with widespread asymptomatic hyperpigmented verrucous
      plaques since 3 months of age. The lesions were distributed in a linear manner
      along Blaschko's lines on trunk and extremities and were accentuated in flexures
      and around joints. There was no history of blistering or redness and no other
      family member was affected. Ichthyosis hystrix (of Curth and Macklin) and
      generalized linear/mosaic epidermolytic hyperkeratosis (EHK) were considered in
      the differential diagnosis. Biopsy from both trunk lesion and lesion on knee
      revealed characteristic epidermolytic hyperkeratosis, thereby clinching the
      diagnosis of systematized linear EHK. 

PMID- 24456952
TI  - Acute onset of a vesiculopustular rash in an ICU patient.
AB  - A 63 year-old woman with hyperthyroidism was admitted to the Medical Intensive
      Care Unit for ARDS following damage to her lungs from propylthiouracil. She was
      placed on 250 mg SSKI PO TID as an alternative therapy until thyroidectomy could
      be performed. Four days after admission, she abruptly developed an acneiform rash
      on her face, shown to be iododerma. The eruption rapidly resolved after
      discontinuation of the SSKI. 

PMID- 24456953
TI  - Treatment of subcutaneous sarcoidosis with hydroxychloroquine: report of 2 cases.
AB  - Although the therapeutic benefit of oral antimalarials in various types of
      sarcoidosis is well described, their reported use specifically in subcutaneous
      sarcoidosis (Darier-Roussy type sarcoidosis) is limited. We describe the cases of
      two patients with subcutaneous sarcoidosis treated with hydroxychloroquine,
      suggesting that it may represent an alternative first-line treatment for patients
      in whom steroid-sparing therapy is desired. 

PMID- 24456954
TI  - Congenital malalignment of the great toenail. Report of two cases.
AB  - Congenital malalignment of the great toenail is characterized by lateral
      deviation of nail plates, which are not parallel to the distal phalanx. We report
      two cases of congenital malalignment of the great toenail in two otherwise
      healthy children. Because this entity is probably underdiagnosed, a high index of
      suspicion is required to prevent from diagnostic errors and unnecessary
      treatments. 

PMID- 24456955
TI  - Traumatic neuroma of the penis.
AB  - Traumatic neuromas are tumors produced by a reactive process to regenerate
      injured nerves that result in a disordered proliferation of nerve bundles. These
      tumors are usually related to previous surgery or trauma. We describe a case of
      traumatic neuroma on the penis of a 24-year-old man; the tumor was initially
      suspected to be a condyloma. A shave biopsy was both diagnostic and curative. 

PMID- 24456956
TI  - Verruciform xanthoma.
AB  - A 50-year-old man presented with a several month history of a polypoid papule on
      the scrotum. A dense accumulation of macrophages with foamy cytoplasm was
      exhibited in the biopsy specimen leading to a diagnosis of verruciform xanthoma. 

PMID- 24456957
TI  - Getting to the point: a case of a sewing needle retrieved from the thigh.
AB  - Foreign bodies are rarely retained in the skin after puncture wounds or
      impalement injuries and are even less commonly initially detected several months
      after penetration. Sewing needles are most frequently reported in the literature
      as foreign bodies in cases of ingestion, inoculation of the cranium and heart,
      and penetration of the knee. Herein we describe a case of a middle-aged man who
      presented to the outpatient dermatology clinic with an 8-month history of a
      nodule in his left thigh; he had noted recent onset of mild pain. On examination
      he was found to have a sharp needle-like point palpable below the skin of his
      left lateral thigh. Plain radiographs of the left thigh showed a fractured sewing
      needle overlying the same area. During local incision, two fragments of a sewing
      needle were removed from the lateral thigh. 

PMID- 24456958
TI  - An unusual erysipelas-like presentation.
AB  - A 61-year-old man presented with erysipelas-like cutaneous leishmaniasis. 

PMID- 24456959
TI  - A case of eosinophilic dermatosis of hematologic malignancy in a patient with
      multiple myeloma.
AB  - A 50-year-old man with eosinophilic dermatosis of hematologic malignancy is
      presented. His dermatosis cleared after chemotherapy produced improved control of
      his multiple myeloma. 

PMID- 24456960
TI  - A simplified minimally invasive technique for the treatment of venous lakes.
AB  - A simplified approach to treat venous lakes of the vermillion lip is presented.
      Our method involves the use of a 30 gauge hypodermic needle to deliver a low
      powered, high-frequency electrical current from a hyfrecator power source into
      the venous lake lesion. 

PMID- 24456961
TI  - Generalized morphea successfully treated with extracorporeal photochemotherapy
      (ECP).
AB  - A patient is presented with generalized morphea whose disease completely resolved
      after combination therapy with extracorporeal photopheresis and broad band UVA
      treatments. 

PMID- 24456962
TI  - Herpes zoster in a 2-year-old vaccinated against varicella.
AB  - Herpes zoster is uncommon in the pediatric population. We report a case of herpes
      zoster in a 2-year-old boy who received the live attenuated varicella zoster
      virus vaccination at his 12-month pediatric visit. The child was treated with
      acyclovir and recovered without complications. 

PMID- 24456963
TI  - Fish odor syndrome: a case report of trimethylaminuria.
AB  - Trimethylaminuria is a rare, autosomal recessive, metabolic disorder that results
      in accumulation of trimethylamine (TMA), which smells like rotten fish. The
      chemical is excreted in sweat and urine owing to a deficiency in the enzyme
      flavin monooxygenase 3 (FMO3). We report a case of trimethylaminuria in a 12-year
      old girl. The patient failed treatment with diet and hygiene modification, but
      achieved symptomatic improvement after a four-month course of metronidazole. 

PMID- 24456964
TI  - Chemical burn caused by topical application of garlic under occlusion.
AB  - Allium sativum (garlic) can cause an irritant contact dermatitis, secondary to
      naturopathic practices. We report an unusually severe case of chemical burn
      following garlic applied under occlusion. 

PMID- 24456965
TI  - Methodological survey of designed uneven randomization trials (DU-RANDOM): a
      protocol.
AB  - BACKGROUND: Although even randomization (that is, approximately 1:1 randomization
      ratio in study arms) provides the greatest statistical power, designed uneven
      randomization (DUR), (for example, 1:2 or 1:3) is used to increase participation
      rates. Until now, no convincing data exists addressing the impact of DUR on
      participation rates in trials. The objective of this study is to evaluate the
      epidemiology and to explore factors associated with DUR. METHODS: We will search
      for reports of RCTs published within two years in 25 general medical journals
      with the highest impact factor according to the Journal Citation Report (JCR)
      2010. Teams of two reviewers will determine eligibility and extract relevant
      information from eligible RCTs in duplicate and using standardized forms. We will
      report the prevalence of DUR trials, the reported reasons for using DUR, and
      perform a linear regression analysis to estimate the association between the
      randomization ratio and the associated factors, including participation rate,
      type of informed consent, clinical area, and so on. DISCUSSION: A clearer
      understanding of RCTs with DUR and its association with factors in trials, for
      example, participation rate, can optimize trial design and may have important
      implications for both researchers and users of the medical literature.

PMID- 24456967
TI  - Influences on decision for mastectomy in patients eligible for breast conserving
      surgery.
AB  - Increasing emphasis is being placed on low mastectomy rates. Our objective was to
      investigate factors influencing rates of mastectomy and breast conserving
      surgery. A group of 171 patients (27%) who could have had breast conserving
      surgery (BCS) but chose mastectomy was identified as well as all patients who
      underwent BCS over a 6 year period. A questionnaire asking patient's attitudes to
      factors which could influence their choice of operation was compiled and sent to
      this study group. Results showed surgical advice to be the most important factor,
      with significantly more influence in BCS patients. No significant difference was
      found in distance to treatment between the groups. Shorter duration radiotherapy
      would have made 47% of mastectomy patients more likely to accept BCS. BCS rates
      are a poor measure of quality of patient care. More emphasis should be put on
      choices offered to patients rather than overall uptake of a specific choice. 

PMID- 24456966
TI  - Porphyromonas gingivalis oral infection exacerbates the development and severity
      of collagen-induced arthritis.
AB  - INTRODUCTION: Clinical studies suggest a direct influence of periodontal disease
      (PD) on serum inflammatory markers and disease assessment of patients with
      established rheumatoid arthritis (RA). However, the influence of PD on arthritis
      development remains unclear. This investigation was undertaken to determine the
      contribution of chronic PD to immune activation and development of joint
      inflammation using the collagen-induced arthritis (CIA) model. METHODS: DBA1/J
      mice orally infected with Porphyromonas gingivalis were administered with
      collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete
      Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed
      by visual scoring of paw swelling, caliper measurement of the paws, mRNA
      expression, paw micro-computed tomography (micro-CT) analysis, histology, and
      tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive
      immunohistochemistry. Serum and reactivated splenocytes were evaluated for
      cytokine expression. RESULTS: Mice induced for PD and/or arthritis developed
      periodontal disease, shown by decreased alveolar bone and alteration of mRNA
      expression in gingival tissues and submandibular lymph nodes compared to vehicle.
      P. gingivalis oral infection increased paw swelling and osteoclast numbers in
      mice immunized with CFA/CII. Arthritis incidence and severity were increased by
      P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis,
      bone erosions, and osteoclast numbers in the paws were observed following IFA/CII
      immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis
      showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis
      infection was present in mice receiving either CFA/CII or IFA/CII immunizations.
      Significant cytokine increases induced by P. gingivalis oral infection were
      mostly associated to Th17-related cytokines of reactivated splenic cells,
      including IL-1beta, IL-6, and IL-22 in the CFA/CII group and IL-1beta, tumor
      necrosis factor-alpha, transforming growth factor-beta, IL-6 and IL-23 in the
      IFA/CII group. CONCLUSIONS: Chronic P. gingivalis oral infection prior to
      arthritis induction increases the immune system activation favoring Th17 cell
      responses, and ultimately accelerating arthritis development. These results
      suggest that chronic oral infection may influence RA development mainly through
      activation of Th17-related pathways.

PMID- 24456968
TI  - Discordance between number of scintigraphic and perioperatively identified
      sentinel lymph nodes and axillary tumour recurrence.
AB  - BACKGROUND: In breast cancer, sentinel node biopsy is considered the standard
      method to assess the lymph node status of the axilla. Preoperative identification
      of sentinel lymph nodes (SLN) is performed by injecting a radioactive tracer,
      followed by lymphoscintigraphy. In some patients there is a discrepancy between
      the number of lymphoscintigraphically identified sentinel nodes and the number of
      nodes found during surgery. We hypothesized that the inability to find
      peroperatively all the lymphoscintigraphically identified sentinel nodes, might
      lead to an increase in axillary recurrence because of positive SLNs not being
      removed. METHODS: Patients who underwent sentinel node biopsy between January
      2000 and July 2010 were identified from a prospectively collected database. The
      number of lymphoscintigraphically and peroperatively identified sentinel nodes
      were reviewed and compared. Axillary recurrences were scored. RESULTS: 1368
      patients underwent a SLN biopsy. Median follow up was 58.5 months (range 12-157).
      Patient and tumour characteristics showed no significant differences. In 139
      patients (10.2%) the number of radioactive nodes found during surgery was less
      than preoperative scanning (group 1) and in 89.8% (N = 1229) there were equal or
      more peroperative nodes identified than seen lymphoscintigraphically (group 2).
      In group 1, 0/139 patients (0%) developed an axillary recurrence and in the
      second group this was 25/1229 (2.0%) respectively. No significant difference
      between groups regarding axillary recurrence, sentinel node status and distant
      metastasis was found. CONCLUSION: Axillary recurrence rate is not influenced by
      the inability to remove all sentinel nodes during surgery that have been
      identified preoperatively by scintigraphy.

PMID- 24456969
TI  - Efficient desymmetrization of 4,6-di-O-benzyl-myo-inositol by Lipozyme TL-IM.
AB  - The enantioselective enzymatic desymmetrization of 4,6-di-O-benzyl-myo-inositol,
      a myo-inositol derivative, was effectively catalyzed by Thermomyces lanuginosus
      lipase (TL-IM). The product 1D-1-O-acetyl-4,6-di-O-benzyl-myo-inositol, a useful
      precursor to inositol phosphates, was obtained in excellent yield and
      enantiomeric excess. Through the investigation of the effects of solvent,
      biocatalyst load, and temperature, a more economical procedure resulted. The
      feasibility of biocatalyst reuse was also shown. 

PMID- 24456970
TI  - Bacillus thuringiensis: a specific gamma-cyclodextrin producer strain.
AB  - An anaerobic microbial isolate Bacillus species, designated B. thuringiensis GU
      2, was isolated from soil as a specific gamma-cyclodextrin (CD) producer strain
      in alkaline medium under anaerobic conditions. The optimum pH and temperature for
      bacterial growth and gamma-CD production were estimated to be pH 8.5 and 37
      degrees C in the presence of 1.0% starch substrate, respectively. A high purity
      yield >95% of gamma-CD from the total CD yield in the reaction mixture was
      obtained from starch that was supposed to be converted by gamma-cyclodextrin
      glycotransferase, tentatively named as gamma-CGTase. The maximum gamma-CGTase
      activity was estimated at 2.45U/mL under optimized condition. This is the first
      report demonstrating the generation of a specific gamma-cyclodextrin (CD)
      producer strain by the action of a gamma-CGTase under anaerobic conditions. 

PMID- 24456972
TI  - Oswald Avery, DNA, and the transformation of biology.
AB  - Seventy years ago, Oswald Avery and his colleagues from the Rockefeller Institute
      published the first evidence that genes are made of DNA. Their discovery was
      received with a mixture of enthusiasm, suspicion and perplexity. In this article,
      I trace the reasons for these different responses, and show how we need to revise
      our usual explanations of what finally convinced everyone that the Avery group
      was right. 

PMID- 24456971
TI  - People with limiting long-term conditions report poorer experiences and more
      problems with hospital care.
AB  - BACKGROUND: Long-term conditions have a significant impact on individuals, their
      families, and the health service. As people with these conditions represent a
      high proportion of hospital admissions, investigating their experiences of
      inpatient care has become an important area of investigation. We conducted a
      secondary analysis of the NHS adult inpatient survey for England to compare the
      hospital experiences of three groups of patients: those without long-term
      conditions, those with a single long-term condition, and those with multiple long
      term conditions. We were particularly interested in the extent to which these
      patients received self-management support from hospital staff, so we developed a
      brief summary tool drawn from salient questions in the survey to aid the
      comparison. METHODS: Analysis of data from the 2011 national adult inpatient
      survey (n = 65,134) to compare the experiences of three groups of patients: those
      with no limiting long-term conditions (No-LLTC), those with one limiting long
      term condition (S-LLTC), and those with two or more limiting long-term conditions
      (M-LLTC). The main outcome measure was patients' self-reports of their experience
      of inpatient care, including staff-patient interactions, information provision,
      involvement in decisions and support for self-care and overall ratings of care. A
      short form scale, the Oxford Patient Involvement and Experience scale (OxPIE) was
      developed from the adult inpatient survey and used to compare the groups using
      logistic regression. RESULTS: There were significant differences between the No
      LLTC group in comparison to both the S-LLTC and M-LLTC groups. Patients with
      limiting long-term conditions reported significantly worse hospital experiences
      than those without, as measured by OxPIE: S-LLTC odds ratio = 1.23, 95% CI 1.03
      1.48; M-LLTC odds ratio = 1.64, 95% CI 1.19-2.26. Responses to a single global
      rating question were more positive but not strongly correlated with OxPIE.
      CONCLUSIONS: Patients with LLTCs were more critical of their inpatient care than
      those with no LLTCs. Those with more than one long-term condition reported worse
      experiences than those with a single limiting condition. Simple rating questions
      may not be sufficiently sensitive to reflect important aspects of patients'
      experience.

PMID- 24456973
TI  - Trade-offs.

PMID- 24456974
TI  - Coelacanths.

PMID- 24456975
TI  - Range-finding in squid using retinal deformation and image blur.
AB  - Squid and other cephalopods catch prey with remarkable speed and precision [1].
      Before the strike occurs, they encounter the difficult task of judging an
      object's distance and size in the contrast-poor world of the mid-water
      environment [1-4]. Here we describe a solution to this common problem underwater,
      where a large portion of a squid's dorso-temporal retina is intentionally
      blurred. This apparently counter-adaptive 'retinal bump' is combined with a
      vertical bobbing behavior that scans objects of interest from focused to
      defocused retinal regions. The image focus differential changes sharply at
      precisely the distance equivalent to tentacle length and enables the squid,
      Sepioteuthis lessoniana, to capture prey. This unique range-finding mechanism is
      an adaptation to hunting, defense, and object size identification in an
      environment where the depth cues found on land are less reliable. 

PMID- 24456976
TI  - Perceptual load affects spatial tuning of neuronal populations in human early
      visual cortex.
AB  - Withdrawal of attention from a visual scene as a result of perceptual load
      modulates overall levels of activity in human visual cortex [1], but its effects
      on cortical spatial tuning properties are unknown. Here we show attentional load
      at fixation affects the spatial tuning of population receptive fields (pRFs) in
      early visual cortex (V1-3) using functional magnetic resonance imaging (fMRI). We
      found that, compared to low perceptual load, high perceptual load yielded a
      'blurrier' representation of the visual field surrounding the attended location
      and a centrifugal 'repulsion' of pRFs. Additional data and control analyses
      confirmed that these effects were neither due to changes in overall activity
      levels nor to eye movements. These findings suggest neural 'tunnel vision' as a
      form of distractor suppression under high perceptual load. 

PMID- 24456977
TI  - Kinetochore signalling: the KIss that MELTs Knl1.
AB  - Mitotic kinetochores coordinate chromosome bi-orientation and anaphase onset by
      serving as scaffolds for the recruitment of regulatory proteins. Three new
      studies reveal that multiple interaction motifs of the kinetochore protein Knl1
      cooperate to assemble signaling complexes that regulate chromosome segregation. 

PMID- 24456978
TI  - Perception: a motion after-effect for voluntary actions.
AB  - After viewing directional motion for a period of time, we experience a motion
      after-effect in which a subsequent stationary object appears to move in the
      opposite direction. A recent study demonstrates a novel motion after-effect that
      depends on the movement of the hand. 

PMID- 24456979
TI  - Development: the maternal-zygotic transition revisited.
AB  - The handover from maternal to zygotic control has to be carefully orchestrated.
      In most animal embryos, maternal products drive early embryogenesis, and the
      genome of the zygote is only switched on later. However, in the nematode Ascaris
      the zygotic genome is never silent, and the maternal products are rapidly
      eliminated. 

PMID- 24456980
TI  - Organelle size: a cilium length signal regulates IFT cargo loading.
AB  - Cilia grow by assembling structural precursors delivered to their tips by
      intraflagellar transport. New work on ciliary length control indicates that,
      during ciliary growth, cilia send a length signal to the cytoplasm that regulates
      cargo loading onto the constitutively trafficking intraflagellar transport
      machinery. 

PMID- 24456981
TI  - Insect vision: emergence of pattern recognition from coarse encoding.
AB  - Neurogenetic tools of Drosophila research allow unique access to the neural
      circuitry underpinning visually guided behaviours. New research is highlighting
      how particular areas in the fly's central brain needed for pattern recognition
      provide a coarse visual encoding. 

PMID- 24456982
TI  - X-inactivation: Xist RNA uses chromosome contacts to coat the X.
AB  - The mechanisms by which Xist RNA associates with the X chromosome to mediate
      alterations in chromatin structure remain mysterious. Recent genome-wide Xist RNA
      distribution studies suggest that this long noncoding RNA uses 3-dimensional
      chromosome contacts to move to its sites of action. 

PMID- 24456983
TI  - Paleoanthropology: Homo erectus and the limits of a paleontological species.
AB  - The bushy nature of the human evolutionary tree in the past 3 million years is
      widely accepted. Yet, a spectacular new fossil of early Homo has prompted some
      paleoanthropologists to prune our family tree. 

PMID- 24456984
TI  - Paleontology: a cock's comb on a duck-billed dinosaur.
AB  - A soft tissue structure has been discovered on the head of the duck-billed
      dinosaur Edmontosaurus. Its similarity to a cock's comb and other sexually
      dimorphic structures of birds suggests that potential sexual signals existed in
      these extinct animals. 

PMID- 24456985
TI  - Models for the rise of the dinosaurs.
AB  - Dinosaurs arose in the early Triassic in the aftermath of the greatest mass
      extinction ever and became hugely successful in the Mesozoic. Their initial
      diversification is a classic example of a large-scale macroevolutionary change.
      Diversifications at such deep-time scales can now be dissected, modelled and
      tested. New fossils suggest that dinosaurs originated early in the Middle
      Triassic, during the recovery of life from the devastating Permo-Triassic mass
      extinction. Improvements in stratigraphic dating and a new suite of morphometric
      and comparative evolutionary numerical methods now allow a forensic dissection of
      one of the greatest turnovers in the history of life. Such studies mark a move
      from the narrative to the analytical in macroevolutionary research, and they
      allow us to begin to answer the proposal of George Gaylord Simpson, to explore
      adaptive radiations using numerical methods.

PMID- 24456986
TI  - An unusual case of suicide by handcrafted shotgun and slug.
AB  - Injuries by handcrafted firearms are uncommon, and those by handcrafted shotguns
      are very rare. We present an unusual case of suicide using a handcrafted shotgun
      and slug. A 73-year-old male, who was a glass-grinding artisan, was found dead at
      a workshop on the premises of his residence. Autopsy showed a contact shotgun
      wound to the forehead, which perforated the cranium and caused extensive damage
      to the brain. The handcrafted shotgun was found in the proximity of the body. The
      shotgun consisted of metal pipes fixed to the vise and did not take the form of a
      conventional gun. The recovered slug was also found to be manufactured manually.
      It appeared that the handcrafted shotgun was only intended for committing suicide
      using his ballistics knowledge, skills, and resources. 

PMID- 24456987
TI  - Differences and homologies of chromosomal alterations within and between breast
      cancer cell lines: a clustering analysis.
AB  - BACKGROUND: The MCF7 (ER+/HER2-), T47D (ER+/HER2-), BT474 (ER+/HER2+) and SKBR3
      (ER-/HER2+) breast cancer cell lines are widely used in breast cancer research as
      paradigms of the luminal and HER2 phenotypes. Although they have been subjected
      to cytogenetic analysis, their chromosomal abnormalities have not been carefully
      characterized, and their differential cytogenetic profiles have not yet been
      established. In addition, techniques such as comparative genomic hybridization
      (CGH), microarray-based CGH and multiplex ligation-dependent probe amplification
      (MLPA) have described specific regions of gains, losses and amplifications of
      these cell lines; however, these techniques cannot detect balanced chromosomal
      rearrangements (e.g., translocations or inversions) or low frequency mosaicism.
      RESULTS: A range of 19 to 26 metaphases of the MCF7, T47D, BT474 and SKBR3 cell
      lines was studied using conventional (G-banding) and molecular cytogenetic
      techniques (multi-color fluorescence in situ hybridization, M-FISH). We detected
      previously unreported chromosomal changes and determined the content and
      frequency of chromosomal markers. MCF7 and T47D (ER+/HER2-) cells showed a less
      complex chromosomal make up, with more numerical than structural alterations,
      compared to BT474 and SKBR3 (HER2+) cells, which harbored the highest frequency
      of numerical and structural aberrations. Karyotype heterogeneity and clonality
      were determined by comparing all metaphases within and between the four cell
      lines by hierarchical clustering. The latter analysis identified five main
      clusters. One of these clusters was characterized by numerical chromosomal
      abnormalities common to all cell lines, and the other four clusters encompassed
      cell-specific chromosomal abnormalities. T47D and BT474 cells shared the most
      chromosomal abnormalities, some of which were shared with SKBR3 cells. MCF7 cells
      showed a chromosomal pattern that was markedly different from those of the other
      cell lines. CONCLUSIONS: Our study provides a comprehensive and specific
      characterization of complex chromosomal aberrations of MCF7, T47D, BT474 and
      SKBR3 cell lines.The chromosomal pattern of ER+/HER2- cells is less complex than
      that of ER+/HER2+ and ER-/HER2+ cells. These chromosomal abnormalities could
      influence the biologic and pharmacologic response of cells. Finally, although
      gene expression profiling and aCGH studies have classified these four cell lines
      as luminal, our results suggest that they are heterogeneous at the cytogenetic
      level.

PMID- 24456988
TI  - Comparison of image quality in pediatric head computed tomography reconstructed
      using blended iterative reconstruction versus filtered back projection.
AB  - We compared image quality in 44 pediatric head computed tomographic exams
      reconstructed using four levels of blended iterative techniques (iDOSE 1-4)
      versus filtered back projection. Three radiologists reviewed the 220 series in a
      randomized, blinded manner. They scored each series based on gray-white matter
      differentiation, visibility of the pre-pontine cistern, caudate head, image
      noise, and image quality. Noise was measured in the vitreous and the thalamus.
      Composite scores were highest with iDOSE 4 (P<.0001). Interobserver agreement was
      fair to moderate. Spearman's rho of the vitreous (-0.62, P<.001) and thalamus (
      0.58, P<.001) confirmed a significant inverse correlation between iDOSE level and
      noise. 

PMID- 24456989
TI  - Intracranial organizing hematoma with papillary endothelial hyperplasia features
      after resection and involved field radiotherapy for cerebellar juvenile pilocytic
      astrocytoma.
AB  - This article describes a case of organizing hematoma with features of papillary
      endothelial hyperplasia arising at the site of a right cerebellar juvenile
      pilocytic astrocytoma previously treated with surgery and involved-field
      radiation therapy. CTA demonstrated a mass with abnormal vascularity in the
      treatment bed. MRI demonstrated the evolution of the lesion from a cystic mass
      with a heterogeneously enhancing nodule with blood products into a nearly solid
      enhancing mass with abundant areas of susceptibility effect and surrounding
      vasogenic edema. These imaging features warrant considering papillary endothelial
      hyperplasia in the differential diagnosis for a mass that develops after
      radiotherapy. 

PMID- 24456990
TI  - Novel mutations in ATPase 8, ND1 and ND5 genes associated with peripheral
      neuropathy of diabetes.
AB  - Type 2 diabetes (T2D), being a complex, multi factorial metabolic disorder, its
      chronic complications development remains puzzled. In this case report, we
      describe four novel mutations in Cyt b, ATPase 8, ND1 and ND5 genes' synergistic
      activity as plausible factors for the secondary complications of a patient with
      chronic T2D. 

PMID- 24456991
TI  - Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes
      and was associated with decreased insulin resistance and systemic inflammation:
      an open label randomized prospective study from Eastern India.
AB  - Vitamin-D supplementation in vitamin-D insufficient/deficient prediabetes
      individuals is associated with significantly lower progression to diabetes (6/55
      vs. 13/49; p=0.04) and higher reversal to normoglycemia (23/55 vs. 10/49;
      p=0.02), associated with decreased insulin resistance and systemic inflammation
      (TNFalpha and IL6). Baseline vitamin-D and 2h blood glucose independently
      predicted progression to diabetes. 

PMID- 24456992
TI  - The impact of improved glycaemic control with GLP-1 receptor agonist therapy on
      diabetic retinopathy.
AB  - Rapid improvement in glycaemic control with GLP-1 receptor agonist (RA) therapy
      has been reported to be associated with significant progression of diabetic
      retinopathy. This deterioration is transient, and continuing GLP-1 RA treatment
      is associated with reversal of this phenomenon. Pre-existent maculopathy, higher
      grade of retinopathy and longer duration of diabetes may be risk factors for
      persistent deterioration. 

PMID- 24456993
TI  - Comparison of fasting plasma glucose and haemoglobin A1c point-of-care tests in
      screening for diabetes and abnormal glucose regulation in a rural low income
      setting.
AB  - AIMS: Glycated haemoglobin (HbA1C) has been suggested to replace glucose tests in
      identifying diabetes and pre-diabetes. We assessed agreement between fasting
      plasma glucose (FPG) and HbA1C rapid tests in classifying abnormal glucose
      regulation (AGR), and their utility for preventive screening in rural Africa.
      METHODS: A population-based survey of 795 people aged 35-60 years was conducted
      in a mainly rural district in Uganda. FPG was measured using On-Call(r) Plus
      glucometers, and classified using World Health Organization (WHO) and American
      Diabetes Association (ADA) criteria. HbA1C was measured using A1cNow(r) kits and
      classified using ADA criteria. Body mass index and blood pressure were measured.
      Percentage agreement between the two tests was computed. RESULTS: Using HbA1C,
      11.3% of participants had diabetes compared with 4.8% for FPG. Prevalence of
      HbA1C-defined pre-diabetes (26.4%) was 1.2 times and 2.5 times higher than FPG
      defined pre-diabetes using ADA (21.8%) and WHO (10.1%) criteria, respectively.
      With FPG as the reference, agreement between FPG and HbA1C in classifying
      diabetes status was moderate (Kappa=22.9; Area Under the Curve (AUC)=75%), while
      that for AGR was low (Kappa=11.0; AUC=59%). However, agreement was high (over
      90%) among negative tests and among participants with risk factors for type 2
      diabetes (obesity, overweight or hypertension). HbA1C had more procedural
      challenges than FPG. CONCLUSIONS: Although low in the general sample, agreement
      between HbA1C and FPG is excellent among persons who test negative with either
      test. A single test can therefore identify the majority at lower risk for type 2
      diabetes. Nurses if trained can conduct these tests.

PMID- 24456994
TI  - Impact of glycemic variability and hypoglycemia on adverse hospital outcomes in
      non-critically ill patients.
AB  - AIMS: To determine if glycemic variability is associated with hospitalization
      outcomes in non-critically ill patients, and if this association remains after
      controlling for hypoglycemia. METHODS: A retrospective review was performed on
      1276 medical admissions (801 patients) in which insulin was given, >=6 point of
      care glucose (POCG) measurements and length of stay (LOS) 2-30 days. Coefficient
      of variation (%CV) was used to measure glycemic variability. Outcomes included
      LOS and a composite outcome based on ICU transfer, hospital acquired infections,
      and acute renal failure (ARF). RESULTS: There were a median of 18.5 POCG
      measurements per admission with a mean %CV 34.2 +/- 11.1. Hypoglycemia (POCG <=70
      mg/dl [3.9 mmol/l]) occurred in 35.0% of admissions. ICU transfer occurred in
      3.3%, hospital acquired infections 4.8%, ARF 8.3%, and composite outcome 13.5%.
      Adjusting for age, sex, race and Charlson score, every 10 unit increase in %CV
      was associated with an increase in LOS of 0.27 days (p=0.004), while there was no
      association between %CV and the composite outcome. For LOS, there was a
      significant interaction between %CV and hypoglycemia (p=0.07). While there was a
      non-significant correlation in patients without hypoglycemia, LOS correlated
      negatively with %CV in patients with hypoglycemia. When considered simultaneously
      with %CV, hypoglycemia was associated with increased odds of the composite
      outcome [OR 2.03 (95% CI 1.36-3.01), p=<0.001] and an increase of 2 days in LOS
      for those with average %CV. CONCLUSIONS: Hypoglycemia, compared to glycemic
      variability, is more strongly associated with adverse outcomes in hospitalized,
      non-critically ill patients.

PMID- 24456995
TI  - Remaining lifetime risk for developing end stage renal disease among Australian
      Aboriginal people with diabetes.
AB  - The remaining lifetime risks for end stage renal disease among Aboriginal people
      with and without diabetes were estimated. The value for young adults with
      diabetes was high, about 1 in 2 at the age of 30 years, while it decreased with
      age to 1 in 7 at 60 years. 

PMID- 24456996
TI  - Dosimetry of an in-line kilovoltage imaging system and implementation in
      treatment planning.
AB  - PURPOSE: To present the beam properties of the Siemens 70-kV and 121-kV linear
      accelerator-mounted imaging modalities and commissioning of the 121-kV beam in
      the Philips Pinnacle treatment planning system (TPS); measurements in an Alderson
      phantom were performed for verification of the model and to estimate the cone
      beam CT (CBCT) imaging dose in the head and neck, thorax, and pelvis. METHODS AND
      MATERIALS: The beam profiles and depth-dose curve were measured in an acrylic
      phantom using thermoluminescent dosimeters and a soft x-ray ionization chamber.
      Measurements were imported into the TPS, modeled, and verified by phantom
      measurements. RESULTS: Modeling of the profiles and the depth-dose curve can be
      achieved with good quality. Comparison with the measurements in the Alderson
      phantom is generally good; only very close to bony structures is the dose
      underestimated by the TPS. For a 200 degrees  arc CBCT of the head and neck, a
      maximum dose of 7 mGy is measured; the thorax and pelvis 360 degrees  CBCTs give
      doses of 4-10 mGy and 7-15 mGy, respectively. CONCLUSIONS: Dosimetric
      characteristics of the Siemens kVision imaging modalities are presented and
      modeled in the Pinnacle TPS. Thermoluminescent dosimeter measurements in the
      Alderson phantom agree well with the calculated TPS dose, validating the model
      and providing an estimate of the imaging dose for different protocols.

PMID- 24456997
TI  - Making the case for directed organ donation to registered donors in Israel.
AB  - BACKGROUND: The number of deceased donor organ donations in Israel is lower than
      average when compared to other Western World countries. To address the organ gap,
      the 2008 Organ Transplantation Law provides new interventions, including
      important incentives to donors (and their families). The most notable of these
      was granting priority to registered donors (i.e., people on the waiting list who
      signed a donor card). The current study presents the normative arguments as well
      as the first documentation of public attitudes in Israel towards another possible
      incentive - allowing individuals to influence the allocation of their organs by
      permitting them to designate, to direct their donated organs [DD] to other
      registered donors, instead of the current allocation based primarily on medical
      criteria. METHODS: A structured phone survey of 695 Israelis was conducted during
      Feb-March 2012. The sample is representative of the Israeli society in terms of
      age mix and gender, with adequate representation of the Arab and ultra-orthodox
      Jewish subgroups. RESULTS: Among all Israelis, 68% stated a willingness to donate
      their organs, but only 16% reported to have already signed a donor card. 85%
      stated their interest in receiving an organ if the need arises. Overall, 64% of
      respondents felt that DD to a group of others who have registered as donors is
      justified, and the rate was remarkably higher in the Arab group (84%), and lower
      in the religious and ultraorthodox Jewish groups (52% and 50% respectively).
      CONCLUSIONS: The majority of the Israeli public supports organ donation and its
      proven benefits. Thus, organ recovery policy should be grounded in a strong
      communitarian strategy as we all stand to benefit from cooperation. However,
      current legislation and practices are modeled on individual disposition based on
      an opt-in legal framework. DD allows personal choices of to-be donors that might
      interfere with social interests, principles, and values such as equal access to
      care (i.e. organs) or justice. However, based on the result of this survey, the
      conceptual case of DD to other registered donors should be viewed more favorably
      (while the details should be addressed in future analyses), as DD is not expected
      to be rejected by the public at the outset. From a normative perspective, it is
      possible to support an allocation scheme that allows DD to other registered
      donors, where individual preferences that promote just sharing of the burden
      (donating organs) as well as the benefits (receiving an organ) of transplantation
      medicine are respected. Yet, DD to other registered donors should be understood
      and portrayed as a transition step towards a more communitarian model, and as a
      signal of solidarity by sharing organs as a public good rather than as an
      exercise of a quasi-property right.

PMID- 24456998
TI  - An evaluation of the effectiveness of a multi-modal intervention in frail and pre
      frail older people with type 2 diabetes--the MID-Frail study: study protocol for
      a randomised controlled trial.
AB  - BACKGROUND: Diabetes, a highly prevalent, chronic disease, is associated with
      increasing frailty and functional decline in older people, with concomitant
      personal, social, and public health implications. We describe the rationale and
      methods of the multi-modal intervention in diabetes in frailty (MID-Frail) study.
      METHODS/DESIGN: The MID-Frail study is an open, randomised, multicentre study,
      with random allocation by clusters (each trial site) to a usual care group or an
      intervention group. A total of 1,718 subjects will be randomised with each site
      enrolling on average 14 or 15 subjects. The primary objective of the study is to
      evaluate, in comparison with usual clinical practice, the effectiveness of a
      multi-modal intervention (specific clinical targets, education, diet, and
      resistance training exercise) in frail and pre-frail subjects aged >=70 years
      with type 2 diabetes in terms of the difference in function 2 years post
      randomisation. Difference in function will be measured by changes in a summary
      ordinal score on the short physical performance battery (SPPB) of at least one
      point. Secondary outcomes include daily activities, economic evaluation, and
      quality of life. DISCUSSION: The MID-Frail study will provide evidence on the
      clinical, functional, social, and economic impact of a multi-modal approach in
      frail and pre-frail older people with type 2 diabetes. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01654341.

PMID- 24456999
TI  - 'Stand still ..., and move on' , an early neurologically-focused follow-up for
      cardiac arrest survivors and their caregivers: a process evaluation.
AB  - BACKGROUND: A cardiac arrest can lead to hypoxic-ischaemic brain injury which can
      result in cognitive and emotional impairments and may negatively affect daily
      functioning, participation in society and quality of life. Furthermore, the
      impact on the family of the patient can be high. We designed an intervention
      called 'Stand still ..., and move on', which is a concise, individualised, semi
      structured intervention for survivors of cardiac arrest and their caregivers,
      consisting of between one and six face-to-face consultations provided by a
      trained nurse. The intervention is directed at early detection of cognitive and
      emotional problems, provision of information, promotion of self-management and
      referral to specialised care if necessary. The effectiveness of the intervention
      is being examined in a randomised controlled trial [ISRCTN74835019]. Alongside
      this trial we performed a process evaluation which aims to investigate the
      feasibility of the intervention by assessing: 1) the attendance and dose
      delivered; 2) performance according to protocol; and 3) the opinion of patients,
      caregivers and nurses on the intervention. METHODS: Participants of this process
      evaluation were 97 patients allocated to the intervention group of the RCT, their
      91 caregivers, and six nurses who conducted the intervention. Measurement
      instruments used were evaluation forms for patients and caregivers, registration
      and evaluation forms for nurses, and semi-structured interviews with nurses.
      RESULTS: Seventy-nine of the patients (81%) allocated to the intervention group
      and 65 caregivers (71%) participated in the intervention. The mean (SD) number of
      consultations per patient was 1.8 (1.0), and most consultations were conducted at
      the patients' home. The intervention was performed largely according to protocol,
      except that the intervention usually started later than intended, consultations
      were longer than expected, and the topic of self-management was not regularly
      addressed. Patients marked the quality of the intervention with a mean score of
      7.5 and the performance of the nurse with an 8.0 out of ten. Overall, the
      intervention was positively evaluated by patients, caregivers and nurses.
      CONCLUSIONS: The intervention 'Stand still ..., and move on' is a promising
      intervention which was performed largely according to protocol and seems feasible
      for implementation after some adaptations, if it is found to be effective.

PMID- 24457000
TI  - Mortality rate in type 2 myocardial infarction: observations from an unselected
      hospital cohort.
AB  - BACKGROUND: The classification of myocardial infarction into 5 types was
      introduced in 2007. The prognostic impact of this universal definition, with
      particular focus on type 2 myocardial infarction, has not been studied
      prospectively in unselected hospital patients. METHODS: During a 1-year period,
      all hospitalized patients having cardiac troponin I measured were considered. The
      diagnosis of a myocardial infarction was according to the universal definition,
      and specified criteria were used in the classification of type 2 myocardial
      infarction. Follow-up was at least 1 year, with mortality as the end point.
      RESULTS: A total of 3762 consecutive patients were studied, of whom 488 (13%) had
      a myocardial infarction. In 119 patients a type 2 myocardial infarction was
      diagnosed. After a median of 2.1 years (interquartile range, 1.6-2.5 years), 150
      patients had died, with a mortality rate of 49% (58/119) in those with type 2
      myocardial infarction and 26% (92/360) in those with type 1 myocardial infarction
      (P < .0001). In a multivariable Cox regression analysis the following variables
      were independently associated with mortality: current or prior smoker, high age,
      prior myocardial infarction, type 2 myocardial infarction, hypercholesterolemia,
      high p-creatinine, and diabetes mellitus. The multivariable-adjusted hazard ratio
      for type 2 myocardial infarction was 2.0 (95% confidence interval, 1.3-3.0). With
      shock as the only exception, mortality was independent of the triggering
      conditions leading to type 2 myocardial infarction. CONCLUSIONS: Mortality in
      patients with type 2 myocardial infarction is high, reaching approximately 50%
      after 2 years. Further descriptive and survival studies are needed to improve the
      scientific evidence on which treatment of type 2 myocardial infarction is based.

PMID- 24457001
TI  - Ultrasound-assisted dyeing of cellulose acetate.
AB  - The possibility of reducing the use of auxiliaries in conventional cellulose
      acetate dyeing with Disperse Red 50 using ultrasound technique was studied as an
      alternative to the standard procedure. Dyeing of cellulose acetate yarn was
      carried out by using either mechanical agitation alone, with and without
      auxiliaries, or coupling mechanical and ultrasound agitation in the bath where
      the temperature range was maintained between 60 and 80  degrees C. The best
      results of dyeing kinetics were obtained with ultrasound coupled with mechanical
      agitation without auxiliaries (90% of bath exhaustion value at 80  degrees C).
      Hence the corresponding half dyeing times, absorption rate constants according to
      Cegarra-Puente modified equation and ultrasound efficiency were calculated
      confirming the synergic effect of sonication on the dyeing kinetics. Moreover the
      apparent activation energies were also evaluated and the positive effect of
      ultrasound added to mechanical agitation was evidenced by the lower value (48
      kJ/mol) in comparison with 112 and 169 kJ/mol for mechanical stirring alone with
      auxiliaries and without, respectively. Finally, the fastness tests gave good
      values for samples dyed with ultrasound technique even without auxiliaries.
      Moreover color measurements on dyed yarns showed that the color yield obtained by
      ultrasound-assisted dyeing at 80  degrees C of cellulose acetate without using
      additional chemicals into the dye bath reached the same value yielded by
      mechanical agitation, but with remarkably shorter time.

PMID- 24457002
TI  - Micro-molding with ultrasonic vibration energy: new method to disperse nanoclays
      in polymer matrices.
AB  - Ultrasound technology was proved as an efficient processing technique to obtain
      micro-molded specimens of polylactide (PLA) and polybutylene succinate (PBS),
      which were selected as examples of biodegradable polyesters widely employed in
      commodity and specialty applications. Operational parameters such as amplitude,
      molding force and processing time were successfully optimized to prepare samples
      with a decrease in the number average molecular weight lower than 6%. Ultrasonic
      waves also seemed an ideal energy source to provide effective disaggregation of
      clay silicate layers, and therefore exfoliated nanocomposites. X-ray diffraction
      patterns of nanocomposites prepared by direct micro-molding of PLA or PBS powder
      mixtures with natural montmorillonite or different organo-modified clays showed
      the disappearance of the 001 silicate reflection for specimens having up to 6
      wt.% clay content. All electron micrographs revealed relatively homogeneous
      dispersion and sheet nanostructures oriented in the direction of the melt flow.
      Incorporation of clay particles during processing had practically no influence on
      PLA characteristics but enhanced PBS degradation when an organo-modifier was
      employed. This was in agreement with thermal stability data deduced from
      thermogravimetric analysis. Cold crystallization experiments directly performed
      on micro-molded PLA specimens pointed to a complex influence of clay particles
      reflected by the increase or decrease of the overall non-isothermal
      crystallization rate when compared to the neat polymer. In all cases, the
      addition of clay led to a clear decrease in the Avrami exponent.

PMID- 24457003
TI  - High mechanical strain of primary intervertebral disc cells promotes secretion of
      inflammatory factors associated with disc degeneration and pain.
AB  - INTRODUCTION: Excessive mechanical loading of intervertebral discs (IVDs) is
      thought to alter matrix properties and influence disc cell metabolism,
      contributing to degenerative disc disease and development of discogenic pain.
      However, little is known about how mechanical strain induces these changes. This
      study investigated the cellular and molecular changes as well as which
      inflammatory receptors and cytokines were upregulated in human intervertebral
      disc cells exposed to high mechanical strain (HMS) at low frequency. The impact
      of these metabolic changes on neuronal differentiation was also explored to
      determine a role in the development of disc degeneration and discogenic pain.
      METHODS: Isolated human annulus fibrosus (AF) and nucleus pulposus (NP) cells
      were exposed to HMS (20% cyclical stretch at 0.001 Hz) on high-extension silicone
      rubber dishes coupled to a mechanical stretching apparatus and compared to static
      control cultures. Gene expression of Toll-like receptors (TLRs), neuronal growth
      factor (NGF) and tumour necrosis factor alpha (TNFalpha) was assessed. Collected
      conditioned media were analysed for cytokine content and applied to rat
      pheocromocytoma PC12 cells for neuronal differentiation assessment. RESULTS: HMS
      caused upregulation of TLR2, TLR4, NGF and TNFalpha gene expression in IVD cells.
      Medium from HMS cultures contained elevated levels of growth-related oncogene,
      interleukin 6 (IL-6), IL-8, IL-15, monocyte chemoattractant protein 1 (MCP-1),
      MCP-3, monokine induced by gamma interferon, transforming growth factor beta1,
      TNFalpha and NGF. Exposure of PC12 cells to HMS-conditioned media resulted in
      both increased neurite sprouting and cell death. CONCLUSIONS: HMS culture of IVD
      cells in vitro drives cytokine and inflammatory responses associated with
      degenerative disc disease and low-back pain. This study provides evidence for a
      direct link between cellular strain, secretory factors, neoinnervation and
      potential degeneration and discogenic pain in vivo.

PMID- 24457004
TI  - Biological, socio-demographic, work and lifestyle determinants of sitting in
      young adult women: a prospective cohort study.
AB  - BACKGROUND: Sitting is associated with health risks. Factors that influence
      sitting are however not well understood. The aim was to examine the biological,
      socio-demographic, work-related and lifestyle determinants of sitting time
      (including during transport, work and leisure) in young adult Australian women.
      METHODS: Self-reported data from 11,676 participants (aged 22-27 years in 2000)
      in the Australian Longitudinal Study on Women's Health were collected over 9
      years in 2000, 2003, 2006 and 2009. Generalised Estimating Equations were used to
      examine univariable and multivariable associations of body mass index (BMI),
      country of birth, area of residence, education, marital status, number of
      children, occupational status, working hours, physical activity, smoking, alcohol
      intake and stress with week- and weekend-day sitting time. RESULTS: Compared with
      women in the respective referent categories, (1) women with higher BMI, those
      born in Asia, those with less than University level education, doing white collar
      work, working 41-48 hours a week, current smokers, non, rare or risky/high risk
      drinkers and those being somewhat stressed had significantly higher sitting time;
      and (2) women living in rural and remote areas, partnered women, those with
      children, those without a paid job and blue collar workers, those working less
      than 34 hours a week, and active women had significantly lower sitting time.
      CONCLUSIONS: Among young adult Australian women, those with higher BMI, those
      born in Asia, those with higher level occupations and long working hours, were
      most at risk of higher sitting time. These results can be used to identify at
      risk groups and inform intervention development.

PMID- 24457005
TI  - Two cases of laboratory-confirmed leptospirosis in travellers returning to Spain
      from Thailand, September 2013.
AB  - In September 2013, leptospirosis was diagnosed in two Spanish travellers
      returning from Thailand. The first case walked in floodwater in the Phi Phi
      Islands in pouring rain: 20 days later he presented with fever and acute
      hepatitis. The second presented with fever and renal failure 17 days after
      visiting the islands. These cases remind clinicians to consider leptospirosis in
      febrile patients with a history of contact with flood or fresh water while
      travelling to tropical countries.

PMID- 24457006
TI  - Recent infection testing algorithm (RITA) applied to new HIV diagnoses in
      England, Wales and Northern Ireland, 2009 to 2011.
AB  - In 2009, Public Health England (PHE) introduced the routine application of a
      recent infection testing algorithm (RITA) to new HIV diagnoses, where a positive
      RITA result indicates likely acquisition of infection in the previous six months.
      Laboratories submit serum specimens to PHE for testing using the HIV 1/2gO AxSYM
      assay modified for the determination of HIV antibody avidity. Results are
      classified according to avidity index and data on CD4 count, antiretroviral
      treatment and the presence of an AIDS-defining illness. Between 2009 and 2011,
      38.4% (6,966/18,134) of new HIV diagnoses in England, Wales and Northern Ireland
      were tested. Demographic characteristics of those tested were similar to all
      persons with diagnosed HIV. Overall, recent infection was 14.7% (1,022/6,966) and
      higher among men who have sex with men (MSM) (22.3%, 720/3,223) compared with
      heterosexual men and women (7.8%, 247/3,164). Higher proportions were among
      persons aged 15-24 years compared with those >=50 years (MSM 31.2% (139/445) vs
      13.6% (42/308); heterosexual men and women 17.3% (43/249) vs 6.2% (31/501)).
      Among heterosexual men and women, black Africans were least likely to have recent
      infection compared with whites (4.8%, 90/1,892 vs 13.3%, 97/728; adjusted odds
      ratio: 0.6; 95% CI: 0.4-0.9). Our results indicate evidence of ongoing HIV
      transmission during the study period, particularly among MSM.

PMID- 24457007
TI  - Coverage of the English national human papillomavirus (HPV) immunisation
      programme among 12 to 17 year-old females by area-level deprivation score,
      England, 2008 to 2011.
AB  - The English national human papillomavirus (HPV) immunisation programme has
      offered vaccination to girls aged 12 years at the start of each school year since
      September 2008. A catch-up programme has offered vaccination to girls up to 18
      years. Delivery is predominantly school-based, with some general practitioner
      (GP)-based immunisation. The relationship between HPV immunisation coverage and
      deprivation (index of multiple deprivation, IMD) was assessed by geographical
      area (N=151) for each school year offered the HPV vaccine between 2008 to 2011
      using the Spearman's rank correlation coefficient, and compared to that for
      adequate cervical screening of women aged 25 to 49 years. Coverage at age 12
      showed no significant association with IMD at the area-level (p=0.12). Within the
      catch-up years, there was some suggestion of higher deprivation being associated
      with lower coverage. This was not significant for girls offered immunisation
      under 16 years (in compulsory education) (p=0.09), but was more marked and
      statistically significant for older girls (p<0.0001). The proportion of women
      aged 25 to 49 years with an adequate cervical screen was negatively associated
      with deprivation (p<0.0001). School-based HPV immunisation delivery appears to be
      successfully reducing inequalities in cervical cancer control at area-level.
      However, the catch-up cohorts above the age of compulsory education may face
      increased inequality. Further investigation is needed into individual-level
      factors associated with coverage.

PMID- 24457011
TI  - Involvement of TRPV4 channels in Abeta(40)-induced hippocampal cell death and
      astrocytic Ca(2+) signalling.
AB  - Previous studies suggested that amyloid beta (Abeta)-induced disruption of
      astrocytic Ca(2+) signalling and oxidative stress play a major role in the
      progression towards neuronal and glial death in Alzheimer's disease. We have
      recently demonstrated that Ca(2+)-permeable TRPV4 channels are highly expressed
      in rat hippocampal astrocytes and are involved in oxidative stress-induced cell
      damage. The aim of this study was to test the hypothesis that TRPV4 channels also
      contribute to hippocampal damage evoked by Abeta. Synthetic Abeta40 evoked cell
      death in hippocampal slice cultures in a concentration (0-20MUM) and time (12
      48h) dependent manner, after cultures were preconditioned with sublethal
      concentration of buthionine sulfoximine (1.5MUM) which enhanced endogenous ROS
      production. As demonstrated by propidium iodide fluorescence, damage was observed
      in the granule cell layer of the dentate gyrus and to a smaller degree in
      pyramidal neurons of the CA1-CA3 region, as well as in glia cells mainly at the
      edge of the slice. Immunocytochemistry revealed an altered pattern of TRPV4 and
      GFAP protein expression, and reactive astrogliosis surrounding pyramidal CA1-CA3
      neurons. Neuronal and astrocytic damage was attenuated by the antioxidant Trolox,
      TRPV4 channel blockers Gd(3+) and ruthenium red (RR), and a specific inhibitor of
      the redox and Ca(2+)-sensitive phospholipase A2 enzyme (MAFP). In disassociated
      co-cultures of hippocampal neurons and astrocytes without BSO preconditioning,
      Abeta40 evoked pronounced neuronal damage, enhanced the expression of TRPV4 and
      GFAP proteins (indicative of reactive astrogliosis), and increased intracellular
      free Ca(2+) concentration in astrocytes. The latter effect was attenuated by RR
      and in Ca(2+)-free media. These data show that Abeta40 can activate astrocytic
      TRPV4 channels in the hippocampus, leading to neuronal and astrocytic damage in a
      Ca(2+) and oxidative stress-dependent manner. 

PMID- 24457012
TI  - Regulation of the latent-lytic switch in Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) infection contributes to the development of several
      different types of human malignancy, including Burkitt lymphoma, Hodgkin
      lymphoma, and nasopharyngeal carcinoma. As a herpesvirus, EBV can establish
      latent or lytic infection in cells. EBV-positive tumors are composed almost
      exclusively of cells with latent EBV infection. Strategies for inducing the lytic
      form of EBV infection in tumor cells are being investigated as a potential
      therapy for EBV-positive tumors. In this article, we review how cellular and
      viral proteins regulate the latent-lytic EBV switch in infected B cells and
      epithelial cells, and discuss how harnessing lytic viral reactivation might be
      used therapeutically. 

PMID- 24457014
TI  - The incidence and 10-year survival of interval breast cancers in Wales.
AB  - AIM: To evaluate the number of interval cancers (IC) within one screening cycle
      and the overall 10-year survival of IC, including its four main classifications,
      and compare that to screen-detected cancers (SDC). MATERIALS AND METHODS: Within
      Breast Test Wales (BTW), all SDC between the years 1998 and 2001 were included.
      IC that occurred between 1998 and 2003 that had undergone screening between the
      years 1998 and 2001 were also included. These IC were classified into true
      interval (TI), false negative (FN), occult cancer (OCC), and unclassified cancer
      (UCC). BTW received notification of all deaths of women that had undergone
      screening; thus, the 10-year all-cause survival rate was calculated from the date
      of diagnosis and death. RESULTS: During the study period, 199,082 women attended
      screening. Of these, 1020 (0.51%) women had SDC and 692 (0.38%) women developed
      IC. Of the 692 IC, 391 (57.8%) were TI, 120 (17.7%) were FN, 68 (10%) were OCC,
      and 98 (14.5%) were UCC; 15 (2.2%) were not classified. After a 10-year follow-up
      period, the 10-year survival rate (all-cause) for SDC was 81.6%, overall for all
      of IC was 72.4% (OR = 1.67, p < 0.001), TI was 77.5% (OR = 1.00, p = 0.99), FN
      was 55% (OR = 2.36, p < 0.001), OCC was 54.4% (OR = 3.17, p < 0.001), and UCC was
      87.8% (OR = 0.61, p = 0.19). CONCLUSIONS: The overall 10-year survival of IC was
      significantly different to SDC. However, within this, the prognosis of TI was
      similar to SDC, whereas FN and OCC had significantly worse long-term survival.
      Further research is required to identify the underlying cause of poor survival of
      FN and OCC.

PMID- 24457015
TI  - Pancreatic ductal adenocarcinoma: prevalence and diagnostic value of dark
      choledochal ring sign on T2-weighted MRI.
AB  - AIM: To investigate the dark choledochal ring sign on T2-weighted imaging (T2WI)
      as an indicator for pancreatic ductal adenocarcinoma (PDAC) among periampullary
      carcinomas. MATERIALS AND METHODS: Sixty patients with surgically confirmed
      periampullary cancers [30 PDACs, 15 distal common bile duct (CBD) cancers, 13
      ampullary cancers, and two duodenal cancers] who underwent liver magnetic
      resonance imaging (MRI) were included in this study. Two reviewers independently
      evaluated unenhanced and gadoxetic acid-enhanced MRI (T1WI image set), and a
      combined T2WI and T1WI image set for differentiation between PDAC and other
      periampullary carcinomas using a rating scale, and the presence of the dark
      choledochal ring sign on T2WI, for all 60 tumours. RESULTS: In PDAC, the dark
      choledochal ring sign on T2WI was considered positive in 23 cases by observer 1
      and 24 cases by observer 2, but only in one or two CBD cancers, as determined by
      each observer, respectively. This resulted in sensitivities of 76.7% and 80% and
      specificities of 96.7% and 93.3% for observer 1 and 2, respectively, in the
      diagnosis of PDAC. Adding T2WI correctly led to a change of diagnosis in three
      and four cases of PDAC by each observer, respectively. Thus, there were
      significant differences between the two image sets for both observers in
      distinguishing between PDAC and other periampullary carcinomas (p = 0.02).
      CONCLUSION: The presence of the dark choledochal ring sign on axial T2WI could be
      a complementary imaging feature indicative of PDAC to differentiate PDAC from
      other periampullary carcinomas at MRI.

PMID- 24457016
TI  - Imaging findings of papillary breast lesions: a pictorial review.
AB  - The aim of this review is to describe the different imaging appearances of benign
      and malignant papillary breast lesions on mammography, ultrasound, and magnetic
      resonance imaging, according to the World Health Organization histopathological
      classifications. The classification and morphological imaging characteristics of
      papillary lesions remain challenging for pathologists and radiologists. Despite
      the difficulty of classifying these lesions, our review and those of others
      suggest that morphology is associated with clinically meaningful staging and
      outcome implications. Imaging can help to differentiate the forms of papillary
      lesion, but surgical specimens are required for definitive diagnosis in the
      majority of cases. 

PMID- 24457013
TI  - Virus associated malignancies: the role of viral hepatitis in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading fatal cancer worldwide and
      its incidence continues to increase. Chronic viral hepatitis involving either
      hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is the leading
      etiology for HCC, making HCC prevention a major goal of antiviral therapy. While
      recent clinical observations and translational research have enhanced our
      understanding of the molecular mechanisms driving the initiation and progression
      of HCC, much remains unknown. Current data indicates that HCC tumors are highly
      complex and heterogeneous resulting from the aberrant function of multiple
      molecular pathways. This complex biology is responsible, at least in part, for
      the absence of highly efficient target-directed therapies for this deadly cancer.
      Additionally, the direct or indirect effect of HBV and HCV infection on the
      development of HCC is still a contentious issue. Thus, the question remains
      whether viral hepatitis-associated HCC stems from virus-specific factors, and/or
      from a general mechanism involving inflammation and tissue regeneration. In this
      review we summarize general mechanisms implicated in HCC, emphasizing data
      generated by new technologies available today. We also highlight specific
      pathways by which HBV and HCV could be involved in HCC pathogenesis. However,
      improvements to current in vitro and in vivo systems for both viruses will be
      needed to rigorously define the temporal sequence and specific pathway
      dysregulations that drive the strong clinical link between chronic hepatitis
      virus infection and HCC. 

PMID- 24457017
TI  - The effect of age on apparent diffusion coefficient values in normal spleen: a
      preliminary study.
AB  - AIM: To investigate and characterize the effect of age on apparent diffusion
      coefficient (ADC) values in normal spleen. MATERIALS AND METHODS: A population of
      127 patients (age range 10-79 years, mean age 44.4 years) without magnetic
      resonance imaging findings in abdominal scans, was selected over a 5-year period.
      The ADC values of the spleen were analysed in all ages, and dependency of ADC
      values on age was characterized using Spearman's correlation coefficient test.
      RESULTS: A reduction of ADC values with ageing was found in the spleen (r = 
      0.702, p < 0.001). CONCLUSIONS: The ADC values of the spleen decline with age.
      This should be taken into consideration when disease is diagnosed.

PMID- 24457018
TI  - Comparison of three-dimensional isotropic and conventional MR arthrography with
      respect to the diagnosis of rotator cuff and labral lesions: focus on isotropic
      fat-suppressed proton density and VIBE sequences.
AB  - AIM: To compare the diagnostic accuracies of three-dimensional (3D) isotropic
      magnetic resonance arthrography (MRA) using fat-suppressed proton density (PD) or
      volume interpolated breath-hold examination (VIBE) sequences with that of
      conventional MRA for the diagnosis of rotator cuff and labral lesions. MATERIALS
      AND METHODS: Eighty-six patients who underwent arthroscopic surgery were
      included. 3D isotropic sequences were performed in the axial plane using fat
      suppressed PD (group A) in 53 patients and using VIBE (group B) in 33 patients.
      Reformatted images were obtained corresponding to conventional images, and
      evaluated for the presence of labral and rotator cuff lesions using conventional
      and 3D isotropic sequences. The diagnostic performances of each sequence were
      determined using arthroscopic findings as the standard. RESULTS: Good to
      excellent interobserver agreements were obtained for both 3D isotropic sequences
      for the evaluation of rotator cuff and labral lesions. Excellent agreement was
      found between two-dimensional (2D) and 3D isotropic MRA, except for supraspinatus
      tendon (SST) tears by both readers and for subscapularis tendon (SCT) tears by
      reader 2 in group B. 2D MRA and 3D isotropic sequences had high diagnostic
      performances for rotator and labral tears, and the difference between the two
      imaging methods was insignificant. CONCLUSIONS: The diagnostic performances of 3D
      isotropic VIBE and PD sequences were similar to those of 2D MRA.

PMID- 24457019
TI  - Statins combined with exercise are associated with the increased renal function
      mediated by high-molecular-weight adiponectin in coronary artery disease
      patients.
AB  - BACKGROUND: Statins and exercise therapy are clinically effective in preventing
      cardiovascular events in patients with coronary artery disease (CAD). The aim of
      this study was to determine the effects of statins combined with exercise on the
      renal function of CAD patients. METHODS: We performed a sub-analysis of a
      clinical trial that determined the 20-week-effects of two statins (rosuvastatin,
      n=14; atorvastatin, n=14) combined with regular exercise on renal function, as
      assessed by the estimated glomerular filtration rates (eGFRs) of CAD patients.
      RESULTS: The combination of statins and exercise therapy increased eGFRs from
      61.1+/-16.6 at baseline to 65.8+/-16.8ml/min/per 1.73m(2) (p=0.03), increased
      serum levels of high-molecular-weight (HMW) adiponectin, increased ubiquinol/low
      density lipoprotein cholesterol (LDL-C) ratios, and decreased high sensitivity C
      reactive protein (hs-CRP). Changes in HMW-adiponectin, ubiquinol/LDL-C ratios and
      hs-CRP were significantly correlated with changes in eGFR (r=0.597, p=0.001;
      r=0.437, p=0.02; and r=-0.473, p=0.01, respectively). Treatment-induced increases
      in HMW-adiponectin independently correlated with the increases in eGFR
      (beta=0.513, p=0.02) in a multivariate analysis. Both atorvastatin and
      rosuvastatin combined with regular exercise produced increases in eGFR. The
      patients treated with rosuvastatin exhibited significant improvements in eGFR.
      CONCLUSION: Statins combined with exercise significantly increased eGFR in CAD
      patients, and these improvements in renal function were correlated with increases
      in HMW-adiponectin levels. The statins-exercise combination treatment may have
      provided clinical benefits for patients with CAD partly through the improvement
      in renal function.

PMID- 24457020
TI  - Variables correlated with elderly referral from nursing homes to general
      hospitals.
AB  - BACKGROUND: Referring patients from nursing homes to general hospitals exposes
      them to nosocomial diseases, and may result in the development of a broad
      spectrum of physical, mental and social damages. Therefore, minimizing the
      referring of nursing home patients to hospitals is an important factor for
      keeping the elderly healthy and minimizing health expenditures. In this study we
      examined the variables related to the referral rates from nursing homes to
      general hospitals and the relationship between the referral and the mortality
      rates among the elderly who live in nursing homes in the Haifa Sub-district.
      METHODS: Thirty-two nursing homes were included in a cross-sectional study. All
      medical directors and head nurses were interviewed using a structured
      questionnaire between November 2006 and October 2007. Statistical analysis,
      including the ANOVA and the nonparametric Spearman tests, were employed to
      determine the factors that influence referral rates and the correlation between
      referral rates and mortality rates. RESULTS: The referral rate ranged between 18
      and 222 per 100 financed elderly in a single year. In the multivariate analysis,
      the absence of a physician from the nursing home at the time of the referral to
      general hospitals was the only significant variable related to referral rates. No
      significant relationships were found between referral rates and mortality rates.
      CONCLUSIONS: Absence of a significant relationship between referral rates and
      mortality rates may indicate that high referral rates do not necessarily protect
      the elderly from death. Therefore, any recommendations issued by the Ministry of
      Health (MOH) should emphasize in-house treatment rather than hospitalization.
      Clear instructions on referral from nursing homes to general hospitals need to be
      constructed by the MOH. The MOH should increase the presence of physicians in the
      nursing homes, especially, when the need to refer a patient arises. Further
      quantitative and epidemiologic studies should be conducted in order to, more
      fully and reliably, create guidelines for policy recommendations.

PMID- 24457021
TI  - [Misoprostol: off-label use in the treatment of post-partum hemorrhage].
AB  - INTRODUCTION: Current knowledge on off-label use of misoprostol for prevention
      and treatment of post-partum haemorrhage (PPH). MATERIALS AND METHODS: Systematic
      review of French and English literature by searching in PubMed, The Cochrane
      Library and recommendations of international scholarly societies and the World
      Health Organization. RESULTS: Oral misoprostol reduces the risk of severe PPH
      (>=1L) by more than 80% when compared to a placebo (P<0.02, RR 0.20 [0.04-0.91]),
      and reduces the risk of moderate PPH (500 mL) by almost 50% (P<0.0001, RR 0.53
      [0.39-0.74]). These results are confirmed by numerous studies. On the other hand,
      compared to oxytocin, misoprostol is slightly less efficient in preventing PPH.
      Severe PPH is significantly more frequent in patients receiving misoprostol when
      compared to those receiving 10 IU of syntocinon intravenously or intramuscularly
      (RR 1.39 [1.19-1.63]). Use of misoprostol is associated with a higher risk of
      using other uterotonics (P<0.001). Regarding treatment of PPH, misoprostol (800
      MUg sublingual) could be an alternative to oxytocin (40 IU intravenous) when the
      later is not available. Active bleeding is equivalently stopped with misoprostol
      and with oxytocin (RR 1.12 [0.92-1.37]). However, more side effects are recorded
      with misoprostol, especially diarrhoea, nausea and vomiting but also tremors (RR
      2.80 [2.25-3.49]) and fever above 38 degrees C (RR 8.07 IC [5.52-11.8]).
      CONCLUSION: In prevention of PPH, a single dose of 600 MUg of misoprostol
      sublingual (3 tablets of 200 MUg) can be indicated during the third stage of
      labour, when oxytocin is not available. For treatment of PPH caused by uterine
      atony, a single dose of 800 MUg of misoprostol sublingual (4 tablets of 200 MUg)
      can be indicated if oxytocin is not an option. Combined use of misoprostol and
      oxytocin has not been proved to be more efficient.

PMID- 24457022
TI  - [Prevalence of burnout among obstetrics and gynecology residents].
AB  - OBJECTIVES: Prevalence assessment of burnout among obstetrics and gynecology
      residents and predisposing factors. PATIENTS AND METHODS: Multicentric cross
      sectional survey based on a questionnaire sent by email to the residents
      including demographics data and Maslach Burnout Inventory. RESULTS: Mean burnout
      scores were 19.67+/-10.19 for emotional exhaustion, 33.94+/-5.01 for personal
      accomplishment and 8.72+/-6.10 for depersonalization, corresponding to a moderate
      burnout for each category. High scores of burnout were seen on 19.45 % of
      residents for emotional exhaustion, 33.33 % for depersonalization and 11.11 % for
      personal accomplishment. 36.11 % of residents showed evidence of high burnout in
      emotional exhaustion or depersonalization, and 5.55 % in the three dimensions.
      The number of semesters is correlated with depersonalization (P=0.01).
      CONCLUSION: There is a strong personal accomplishment among obstetrics and
      gynecology residents; however, burnout and emotional exhaustion remains a reality
      during obstetrics and gynecology residency.

PMID- 24457023
TI  - Anicteric hepatoxicity: a potential health risk of occupational exposures in
      Nigerian petroleum oil refining and distribution industry.
AB  - BACKGROUND: Literature abounds linking one's job to certain unpalatable health
      outcomes. Since exposures to hazardous conditions in industrial environments
      often results in sundry health effects among workers, we embarked on this study
      to investigate the hepatic health effects of occupational activities in the
      petroleum refining and distribution industry. METHOD: Biochemical markers of
      liver functions were assayed in plasma, using Reflotron dry chemistry
      spectrophotometric system. The study was conducted on randomly selected workers
      of Port Harcourt Refining Company (PHRC) and Pipelines and Petroleum Product
      Marketing Company (PPMC) both in Alesa-Eleme near Port Harcourt, Nigeria, as well
      as non-oil work civil servants serving as control subjects. RESULT AND
      CONCLUSION: Results showed that, bilirubin ranged 0.3-1.6 mg/dl with a mean of
      0.66+/-0.20mg/dl among the oil workers as against 0.5-1.00mg/dl with a mean of
      0.58+/-0.13mg/dl in non-oil workers, Alkaline phosphatase ranged 50.00-296.00u/l
      (mean: 126.21+/-39.49u/l) in oil workers as against 40.20-111u/l (mean: 66.83+/
      18.54u/l) for non-oil workers, Aspartic transaminases (AST) ranged 5.80-140.20u/l
      (mean: 21.81+/-11.49u/l) in oil workers against 18.00-44.00u/l (mean: 26.89+/
      6.99u/l) for non-oil workers, while Alanine transaminases (ALT) ranged 4.90
      86.00u/l (mean: 22.14+/-11.28u/l) in oil workers as against 10.00-86.60u/l (mean:
      22.30+/-10.22u/l) for the non-oil workers. A close study of the results revealed
      that although the mean values for all the studied parameters were still within
      the parametric reference ranges, however, relative to the referents, there were
      significant increases (P<0.05) in plasma bilirubin (though anicteric) and
      alkaline phosphatase that was not matched with a corresponding increase in the
      plasma transaminases, suggesting a possibility that toxic anicteric hepatoxicity
      is part of the potential health effects of sundry exposures in the Nigeria
      petroleum oil refining and distribution industry. Gender differentiation data
      showed that though the mean values for the parameters were higher in males than
      females, the increases were not significant in most cases (P>0.05), whereas data
      for age and exposure period classifications revealed that irrespective of the age
      of the worker, the effects are likely to start after the first five years,
      manifesting fully after the first decade of occupational exposures. Thus, an
      update of industrial/occupational health measures is necessary for a safer and
      healthier work environment.

PMID- 24457024
TI  - Perilous journey: a tour of the ubiquitin-proteasome system.
AB  - Eukaryotic cells are equipped to degrade proteins via the ubiquitin-proteasome
      system (UPS). Proteins become degraded upon their conjugation to chains of
      ubiquitin where they are then directed to the 26S proteasome, a macromolecular
      protease. The transfer of ubiquitin to proteins and their subsequent degradation
      are highly complex processes, and new research is beginning to uncover the
      molecular details of how ubiquitination and degradation take place in the cell.
      We review some of the new data providing insights into how these processes occur.
      Although distinct mechanisms are often observed, some common themes are emerging
      for how the UPS guides protein substrates through their final journey. 

PMID- 24457026
TI  - Mechanisms of endothelial dysfunction in rheumatoid arthritis: lessons from
      animal studies.
AB  - Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease
      characterized by articular and extra-articular manifestations involving
      cardiovascular diseases (CVDs), which account for 30% to 50% of all deaths. In
      patients with RA, atherosclerosis lesions occur earlier and have a more rapid
      evolution than in the general population. Beyond mortality, the impact of CVD on
      quality of life, combined with the associated increase in health-care costs,
      renders CVD in RA a major public health problem. Recent studies showed that
      patients with RA are characterized by the presence of endothelial dysfunction
      (ED), which is recognized as a key event in the development of atherosclerosis.
      By definition, ED is a functional and reversible alteration of endothelial cells,
      leading to a shift of the actions of the endothelium toward reduced vasodilation,
      proinflammatory state and proliferative and prothrombotic properties. Although
      the improvement of endothelial function is becoming an important element of the
      global management of patients with RA, the mechanistic determinants of ED in RA
      are still poorly understood. Animal models of RA provide the unique opportunity
      to unravel the pathophysiological features of ED in RA. The present review
      summarizes the available data on mechanisms underlying ED in animal models of RA
      and proposes attractive prospects in order to discover novel therapeutic
      strategies of RA-associated ED. 

PMID- 24457025
TI  - Development of a stable cell line with an intact PGC-1alpha/ERRalpha axis for
      screening environmental chemicals.
AB  - The estrogen-related receptor alpha (ERRalpha) and the peroxisome proliferator
      activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha) play
      critical roles in the control of several physiological functions, including the
      regulation of genes involved in energy homeostasis. However, little is known
      about the ability of environmental chemicals to disrupt or modulate this
      important bioenergetics pathway in humans. The goal of this study was to develop
      a cell-based assay system with an intact PGC-1alpha/ERRalpha axis that could be
      used as a screening assay for detecting such chemicals. To this end, we
      successfully generated several stable cell lines expressing PGC-1alpha and showed
      that the reporter driven by the native ERRalpha hormone response unit (AAB-Luc)
      is active in these cell lines and that the activation is PGC-1alpha-dependent.
      Furthermore, we show that this activation can be blocked by the ERRalpha
      selective inverse agonist, XCT790. In addition, we find that genistein and
      bisphenol A further stimulate the reporter activity, while kaempferol has minimal
      effect. These cell lines will be useful for identifying environmental chemicals
      that modulate this important pathway. 

PMID- 24457027
TI  - Chemically functionalized carbon films for single molecule imaging.
AB  - Many biological complexes are naturally low in abundance and pose a significant
      challenge to their structural and functional studies. Here we describe a new
      method that utilizes strong oxidation and chemical linkage to introduce a high
      density of bioactive ligands onto nanometer-thick carbon films and enable
      selective enrichment of individual macromolecular complexes at subnanogram
      levels. The introduced ligands are physically separated. Ni-NTA, Protein G and
      DNA/RNA oligonucleotides were covalently linked to the carbon surface. They
      embody negligible mass and their stability makes the functionalized films able to
      survive long-term storage and tolerate variations in pH, temperature, salts,
      detergents, and solvents. We demonstrated the application of the new method to
      the electron microscopic imaging of the substrate-bound C3PO, an RNA-processing
      enzyme important for the RNA interference pathway. On the ssRNA-linked carbon
      surface, the formation of C3PO oligomers at subnanomolar concentrations likely
      mimics their assembly onto ssRNA substrates presented by their native partners.
      Interestingly, the 3D reconstructions by negative stain EM reveal a side port in
      the C3PO/ssRNA complex, and the 15A cryoEM map showed extra density right above
      the side port, which probably represents the ssRNA. These results suggest a new
      way for ssRNAs to interact with the active sites of the complex. Together our
      data demonstrate that the surface-engineered carbon films are suitable for
      selectively enriching low-abundance biological complexes at nanomolar level and
      for developing novel applications on a large number of surface-presented
      molecules. 

PMID- 24457028
TI  - Absorption, distribution and mechanism of action of SYSADOAS.
AB  - Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOA), such as hyaluronic
      acid (HA), chondroitin sulfate (CS) and glucosamine (GlcN) are natural compounds,
      composed of repeating disaccharides, used to treat patients with osteoarthritis
      (OA). Many questions about the kinetics and mechanism of action of SYSADOA remain
      poorly answered. This review examines the data supporting oral absorption and
      body distribution of SYSADOA, and discusses their mechanism of action. SYSADOA
      are absorbed in the small intestine with a bioavailability ranging from 5 to 45%
      and accumulate in articular tissues. The mechanism of action of HA and CS differs
      in several aspects from that of GlcN. Being large molecules, HA and CS do not
      penetrate into chondrocytes, synoviocytes, osteoblast, osteoclast and osteocytes,
      and so elicit the anti-inflammatory effect by engaging membrane receptors, e.g.
      CD44, TLR4, and ICAM1, with a resulting dual effect: impede the fragments of
      extracellular matrix engaging these receptors, cause of inflammatory reaction,
      and block the signal transduction pathways activated by the fragments and so
      diminish the nuclear translocation of pro-inflammatory transcription factors.
      GlcN penetrates into cells by means of glucose transporters. The primary effect
      of GlcN is associated to its ability to O-GlcNAcylate proteins and as a
      consequence, modulates their activity, e.g. decrease nuclear factor-kappaB
      nuclear translocation. GlcN may also affect the transcription of pro-inflammatory
      cytokines by epigenetic mechanisms. The characteristics of the mechanism of
      action support the use of CS combined with GlcN, and suggest that HA and CS shall
      be more effective in initial phases of OA. 

PMID- 24457029
TI  - Using accelerometers and global positioning system devices to assess gender and
      age differences in children's school, transport, leisure and home based physical
      activity.
AB  - BACKGROUND: Knowledge on domain-specific physical activity (PA) has the potential
      to advance public health interventions and inform new policies promoting
      children's PA. The purpose of this study is to identify and assess domains
      (leisure, school, transport, home) and subdomains (e.g., recess, playgrounds, and
      urban green space) for week day moderate to vigorous PA (MVPA) using objective
      measures and investigate gender and age differences. METHODS: Participants
      included 367 Danish children and adolescents (11-16 years, 52% girls) with
      combined accelerometer and Global Positioning System (GPS) data (mean 2.5 days,
      12.7 hrs/day). The Personal Activity and Location Measurement System and a
      purpose-built database assessed data in 15-second epochs to determine PA and
      assign epochs to 4 domains and 11 subdomains. Frequencies and proportions of time
      spent in MVPA were determined and differences assessed using multi-level
      modeling. RESULTS: More than 90% of MVPA was objectively assigned to
      domains/subdomains. Boys accumulated more MVPA overall, in leisure, school and
      transport (all p < 0.05). Children compared with adolescents accumulated more
      MVPA, primarily through more school MVPA (p < 0.05). Boys spent a large
      proportion of time accumulating MVPA in playgrounds, active transport, Physical
      Education, sports facilities, urban green space and school grounds. Girls spent a
      significant proportion of time accumulating MVPA in active transport and
      playgrounds. No gender or age differences were found in the home domain.
      CONCLUSIONS: Large variations were found in PA frequency and intensity across
      domains/subdomains. Significant gender differences were found, with girls being
      less active in almost all domains and subdomains. Objectively measured patterns
      of PA across domains/subdomains can be used to better tailor PA interventions and
      inform future policies for promoting child PA.

PMID- 24457030
TI  - A multiscale poromicromechanical approach to wave propagation and attenuation in
      bone.
AB  - Ultrasonics is an important diagnostic tool for bone diseases, as it allows for
      non-invasive assessment of bone tissue quality through mass density-elasticity
      relationships. The latter are, however, quite complex for fluid-filled porous
      media, which motivates us to develop a rigorous multiscale poromicrodynamics
      approach valid across the great variety of different bone tissues. Multiscale
      momentum and mass balance, as well as kinematics of a hierarchical double porous
      medium, together with Darcy's law for fluid flow and micro-poro-elasticity for
      the solid phase of bone, give access to the so-called dispersion relation,
      linking the complex wave numbers to corresponding wave frequencies.
      Experimentally validated results show that 2.25 MHz acoustical signals transmit
      healthy cortical bone (exhibiting a low vascular porosity) only in the form of
      fast waves, agreeing very well with experimental data, while both fast and slow
      waves transmit highly osteoporotic as well as trabecular bone (exhibiting a large
      vascular porosity). While velocities and wavelengths of both fast and slow waves,
      as well as attenuation lengths of slow waves, are always monotonously increasing
      with the permeability of the bone sample, the attenuation length of fast waves
      shows a minimum when considered as function of the permeability.

PMID- 24457031
TI  - Effects of experimental configuration on the detection threshold of hysteretic
      elastic nonlinearity.
AB  - Nonlinear elastic signature of granular consolidated or damaged media is often
      very small and might easily fall within the noise level. Therefore, it is
      important to determine an excitation amplitude threshold above which nonlinear
      measurements start to be meaningful. In this paper, we analyze the way this
      threshold is influenced by some parameters of the experimental configuration,
      such as the receiver position, and of the data analysis, such as the considered
      reference amplitude. Furthermore, this contribution shows that extracting
      absolute values of the nonlinear parameters often requires the a priori knowledge
      of the resonance structure of the medium. 

PMID- 24457032
TI  - A comparison between ultrasonic array beamforming and super resolution imaging
      algorithms for non-destructive evaluation.
AB  - In this paper the total focusing method, the so called gold standard in classical
      beamforming, is compared with the widely used time-reversal MUSIC super
      resolution technique in terms of its ability to resolve closely spaced scatterers
      in a solid. The algorithms are tested with simulated and experimental array data,
      each containing different noise levels. The performance of the algorithms is
      evaluated in terms of lateral resolution and sensitivity to noise. It is shown
      that for the weak noise situation (SNR>20 dB), time-reversal MUSIC provides
      significantly enhanced lateral resolution when compared to the total focusing
      method, breaking the diffraction limit. However, for higher noise levels, the
      total focusing method is shown to be robust, whilst the performance of time
      reversal MUSIC is degraded. The influence of multiple scattering on the imaging
      algorithms is also investigated and shown to be small.

PMID- 24457033
TI  - Comorbid atypical depression in borderline personality disorder is common and
      correlated with anxiety-related psychopathology.
AB  - BACKGROUND: The core features of borderline personality disorder (BPD) are
      affective instability, unstable relationships and identity disturbance. Axis I
      comorbidities are frequent, in particular affective disorders. The concept of
      atypical depression is complex and often underestimated. The purpose of the study
      was to investigate the comorbidity of atypical depression in borderline patients
      regarding anxiety-related psychopathology and interpersonal problems. METHODS:
      Sixty patients with BPD were assessed with the Structured Clinical Interviews for
      DSM-IV Axis I and II Disorders (SCID I, SCID II) as well as the Atypical
      Depression Diagnostic Scale (ADDS). Additionally, patients completed a
      questionnaire (SCL-90-R, BDI, STAI, STAXI, IIP-C). RESULTS: Forty-five BPD
      patients (81.8%) had a comorbid affective disorder of which 15 (27.3%) were
      diagnosed with an atypical depression. In comparison to patients with major
      depressive disorder or no comorbid depression, patients with atypical depression
      showed significant higher scores in psychopathological symptoms regarding anxiety
      and global severity as well as interpersonal problems. CONCLUSIONS: The presence
      of atypical depression in borderline patients is correlated with psychopathology,
      anxiety, and interpersonal problems and seems to be of clinical importance for
      personalized treatment decisions.

PMID- 24457034
TI  - The association between suicidality and Internet addiction and activities in
      Taiwanese adolescents.
AB  - OBJECTIVE: The aims of this cross-sectional study were to examine the
      associations of suicidal ideation and attempt with Internet addiction and
      Internet activities in a large representative Taiwanese adolescent population.
      METHODS: 9510 adolescent students aged 12-18 years were selected using a
      stratified random sampling strategy in southern Taiwan and completed the
      questionnaires. The five questions from the Kiddie Schedule for Affective
      Disorders and Schizophrenia were used to inquire as to the participants' suicidal
      ideation and attempt in the past one month. The Chen Internet Addiction Scale was
      used to assess participants' Internet addiction. The kinds of Internet activities
      that the adolescents participated in were also recorded. The associations of
      suicidal ideation and attempt with Internet addiction and Internet activities
      were examined using logistic regression analysis to control for the effects of
      demographic characteristics, depression, family support and self-esteem. RESULTS:
      After controlling for the effects of demographic characteristics, depression,
      family support and self-esteem, Internet addiction was significantly associated
      with suicidal ideation and suicidal attempt. Online gaming, MSN, online searching
      for information, and online studying were associated with an increased risk of
      suicidal ideation. While online gaming, chatting, watching movies, shopping, and
      gambling were associated with an increased risk of suicidal attempt, watching
      online news was associated with a reduced risk of suicidal attempt. CONCLUSIONS:
      The results of this study indicated that adolescents with Internet addiction have
      higher risks of suicidal ideation and attempt than those without. Meanwhile,
      different kinds of Internet activities have various associations with the risks
      of suicidal ideation and attempt.

PMID- 24457035
TI  - Validation of screening questions and symptom coherence of night eating in the
      Swedish Twin Registry.
AB  - BACKGROUND: Screening criteria have been used to estimate the prevalence of night
      eating syndrome (NES), but no validation studies have been conducted. METHOD: We
      examined the validity of two screening questions for NES using a structured
      interview with adults enrolled in the Swedish Twin Study of Adults: Genes and
      Environment (STAGE) study. We also examined the coherence of the proposed
      diagnostic criteria for NES. A total of 416 participants (men=179; women=237)
      completed the interview and reported complete data for study inclusion. RESULTS:
      The following values were calculated for the screening items after confirmation
      by interview for men and women, respectively: positive predictive value=.66 and
      .67, negative predictive value=.52 and .45, sensitivity=.62 and .63, and
      specificity=.56 and .50. As increasingly stringent diagnostic criteria were
      applied to the sample, prevalence of NES dropped. Nocturnal ingestions were more
      likely to co-occur with other NES symptoms than evening hyperphagia, which
      occurred frequently, but often in isolation; women were more likely to report a
      co-occurrence of symptoms than men, who were not likely to report distress
      related to NES symptoms. CONCLUSION: In sum, almost two-thirds of participants
      were correctly identified as having NES (without considering distress or
      impairment) if they answered positively on the screening questions, and about
      half of the participants were correctly identified as not having NES when
      answering negatively on the screening questions. Although self-report questions
      are somewhat informative, a structured interview remains the gold standard for
      diagnosing NES.

PMID- 24457037
TI  - Verbal working memory deficits predict levels of auditory hallucination in first
      episode psychosis.
AB  - BACKGROUND: Auditory verbal hallucinations are a characteristic symptom in
      schizophrenia. Recent causal models of auditory verbal hallucinations propose
      that cognitive mechanisms involving verbal working memory are involved in the
      genesis of auditory verbal hallucinations. Thus, in the present study, we
      investigate the hypothesis that verbal working memory is a specific factor behind
      auditory verbal hallucinations. METHODS: In the present study, we investigated
      the association between verbal working memory manipulation (Backward Digit Span
      and Letter-Number Sequencing) and auditory verbal hallucinations in a population
      study (N=52) of first episode psychosis. The degree of auditory verbal
      hallucination as reported in the P3-subscale of the PANSS interview was included
      as dependent variable using sequential multiple regression, while controlling for
      age, psychosis symptom severity, executive cognitive functions and simple
      auditory working memory span. RESULTS: Multiple sequential regression analyses
      revealed verbal working memory manipulation to be the only significant predictor
      of verbal hallucination severity. CONCLUSIONS: Consistent with cognitive data
      from auditory verbal hallucinations in healthy individuals, the present results
      suggest a specific association between auditory verbal hallucinations, and
      cognitive processes involving the manipulation of phonological representations
      during a verbal working memory task.

PMID- 24457036
TI  - Facial emotion recognition in first-episode schizophrenia and bipolar disorder
      with psychosis.
AB  - Patients with schizophrenia and bipolar disorder have difficulties recognizing
      facial expressions of emotion. Differences in deficits between these disorders
      and the effects of treating acute symptoms of illness with antipsychotic
      medication on these deficits are not well characterized. First-episode patients
      with schizophrenia (n=24) and psychotic bipolar I disorder (n=16) were compared
      to a healthy control group (n=32) on the Penn Emotional Acuity Test. Patients
      were studied during an acute psychotic episode and after seven weeks of treatment
      with antipsychotic medication. During acute psychosis, bipolar patients showed
      deficits recognizing subtle facial expressions of happiness and sadness, and this
      deficit did not resolve with treatment. Schizophrenia patients similarly had
      difficulty recognizing subtle happy faces during acute illness that also did not
      resolve with treatment. In addition, problems recognizing subtle expressions of
      sadness among schizophrenia patients were apparent after treatment. Poorer
      emotion recognition at follow-up was related to negative symptom severity for
      schizophrenia patients. These findings highlight the severity and persistence of
      emotion recognition deficits early in the course of psychotic bipolar disorder
      and schizophrenia, and demonstrate an association of emotion processing deficits
      to negative symptoms in schizophrenia during periods of relative clinical
      stability. 

PMID- 24457039
TI  - Rectourethral fistula secondary to a bowel management system.
AB  - A 67-year-old Caucasian male was admitted under the vascular team with critical
      lower limb ischaemia. Bypass surgery was performed and he was admitted to the
      intensive care unit post-operatively. The patient experienced a turbulent post
      operative recovery complicated by pneumonia, poor respiratory wean and faecal
      incontinence. A bowel management system was inserted but after 18 days it was
      reported faecal matter was bypassing his catheter. A CT scan demonstrated an area
      of necrosis where the bowel management system had been sited which formed a
      rectourethral fistula. Bowel management systems are frequently used in intensive
      care unit settings where a high proportion of patients suffer from faecal
      incontinence. If used correctly they can reduce skin contamination, infection and
      maintain patient hygiene. However, appropriate assessment and investigations
      should be addressed before inserting such devices. This case report highlights
      serious adverse effects of these devices and describes the first documented case
      of these devices causing a rectourethral fistula. 

PMID- 24457038
TI  - Economic development, urbanization, technological change and overweight: what do
      we learn from 244 Demographic and Health Surveys?
AB  - Obesity and overweight are spreading fast in developing countries, and have
      reached world record levels in some of them. Capturing the size, patterns and
      trends of the problem has, however, been severely hampered by the lack of
      comparable data in low and middle income countries. We seek to begin to fill this
      gap by testing several hypotheses on the determinants/correlates of overweight
      among women, related to the influence of economic and technological development.
      We undertake econometric analysis of nationally representative data on about
      878,000 women aged 15-49 from 244 Demographic and Health Surveys (DHS) for 56
      countries over the years 1991-2009. Our findings support most previously
      expressed hypotheses of what might explain obesity patterns in developing
      countries, but they also reject some prior notions and add considerable nuance to
      the emerging pattern. 

PMID- 24457040
TI  - RAD51 Gene 135G/C polymorphism and the risk of four types of common cancers: a
      meta-analysis.
AB  - OBJECTIVES: RAD51 gene plays an important role in the pathogenesis of squamous
      cell carcinoma of the head and neck (SCCHN), colorectal cancer, ovarian cancer
      and acute leukaemia. A number of studies assessed the association between RAD51
      135G/C polymorphism and the risk of these cancers in different population.
      However, the results have been inconclusive. We performed a systematic meta
      analysis to evaluate the association between RAD51 135G/C polymorphism and the
      risk of these four types of cancer. METHODS: Pubmed, Cochrane library and Chinese
      Biomedical Literature Database (CBM) were searched for case-control studies on
      RAD51 135G/C polymorphism and the risk of SCCHN, colorectal cancer, ovarian
      cancer and acute leukaemia published up to Oct 31, 2013. Odds ratios (ORs) with
      95% confidence intervals (CIs) were used to assess the strength of association.
      RESULTS: A total of twenty-two published studies, with 6836 cases and 8507
      controls were included. Overall, no significant association was found between
      RAD51 135G/C polymorphism and the risk of the four types of cancers (G/G vs. C/C:
      OR = 0.83, 95% CI: 0.43-1.59, P = 0.57). However, there was a significant
      association between this polymorphism and SCCHN risk in the subgroup analysis by
      cancer type (G/G vs. C/C: OR = 2.46, 95% CI: 1.08-5.61, P = 0.03). CONCLUSION:
      The RAD51 135G/C polymorphism was associated with the risk of SCCHN. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1383180234106945.

PMID- 24457041
TI  - Low doses of the selective adenosine A2A receptor agonist CGS21680 are protective
      in a rat model of transient cerebral ischemia.
AB  - Evidence indicate that adenosine A2A receptor subtype is of critical importance
      in stroke. An overexpression of A2A adenosine receptors occurs at central level
      on neurons and microglia of ischemic striatum and cortex after focal ischemia.
      Adenosine A2A receptor subtype is localized not only at central level but also
      peripherally on blood cells, where it is known to exert antiinflammatory effect.
      Purpose of the present work was to investigate the putative neuroprotective
      effect of the adenosine A2A receptor agonist CGS21680 in a rat model of transient
      medial cerebral artery occlusion (MCAo). Transient cerebral ischemia was induced
      by 1h occlusion of MCA. CGS21680 (0.01 and 0.1mg/kg, i.p.) was administered
      starting 4h after ischemia according to a chronic protocol (twice/day for 7
      days). CGS21680, at the dose of 0.1mg/kg transiently increased heart frequency
      but did not modify blood pressure. At the dose of 0.01mg/kg the drug did not
      modify either heart frequency or blood pressure. Following transient MCAo,
      CGS21680 at both doses protected from neurological deficit from the first day up
      to 7 days thereafter. At this time, it has reduced microgliosis, astrogliosis and
      improved myelin organization in the striatum and cytoarchitecture of the ischemic
      cortex and striatum. Two days after transient MCAo, CGS21680 has reduced the
      number of infiltrated granulocytes into the ischemic tissue. Data indicate that
      CGS21680 systemically administered is protective by immunosuppressive effects. 

PMID- 24457042
TI  - Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in
      female rats.
AB  - Cancer is associated with an increased prevalence of depression. Peripheral
      tumors induce inflammatory cytokine production in the brain and depressive-like
      behaviors. Mounting evidence indicates that cytokines are part of a pathway by
      which peripheral inflammation causes depression. Neuroinflammatory responses to
      immune challenges can be exacerbated (primed) by prior immunological activation
      associated with aging, early-life infection, and drug exposure. This experiment
      tested the hypothesis that peripheral tumors likewise induce neuroinflammatory
      sensitization or priming. Female rats with chemically-induced mammary carcinomas
      were injected with either saline or lipopolysaccharide (LPS, 250MUg/kg; i.p.),
      and expression of mRNAs involved in the pathway linking inflammation and
      depression (interleukin-1beta [Il-1beta], CD11b, IkappaBalpha, indolamine 2,3
      deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and
      frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il
      1beta and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido
      expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il
      1beta and CD11b expression were positively correlated with tumor weight; heavier
      tumors, in turn, were characterized by more inflammatory, necrotic, and
      granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in
      response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor
      bearing relative to tumor-free rats, IkappaBalpha was greater in hippocampus, and
      Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor
      bearing rats were accompanied by attenuated body weight gain post-LPS. The data
      indicate that neuroinflammatory pathways are potentiated, or primed, in tumor
      bearing rats, which may exacerbate future negative behavioral consequences. 

PMID- 24457043
TI  - beta-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in
      asenescence-accelerated prone 8 mice.
AB  - beta-Asarone is an active component of the Acori graminei rhizome that is a
      traditional Chinese medicine clinically used in treating dementia in China.
      However, the cognitive effect of beta-asarone and its mechanism has remained
      elusive. Here, we used asenescence-accelerated prone 8 (SAMP8) mice, which mimic
      many of the salient features of Alzheimer's disease (AD), to further investigate
      whether modulation of the ROCK signaling pathway and/or autophagy, synaptic loss
      is involved in the effects of beta-asarone on learning and memory. SAMP8 mice at
      the age of 6 months were intragastrically administered by beta-asarone or a
      vehicle daily for 2 months. Senescence-accelerated-resistant (SAMR1) mice were
      used as the control. Our results demonstrate that autophagy and ROCK expression
      were increased significantly in 8 months SAMP8 mice, which were concomitant with
      that SAMP8 mice at the same age displayed a significant synaptic loss and
      cognitive deficits. The up-regulation of ROCK expression and autophage in the
      hippocampus of SAMP8 were significantly reduced by beta-asarone, and prevents
      synaptic loss and improved cognitive function of the SAMP8 mice. beta-asarone
      decreased neuronophagia and lipofuscin in the hippocampus of SAMP8 mice, but did
      not reduce Abeta42 levels and malondialdehyde levels and superoxide dismutase
      activities. Moreover, suppression of ROCK2 by siRNA significantly reduced the
      effects of beta-asarone on the autophage and synaptic proteins expression in PC12
      cells damage induced by Abeta1-40. Taken together, beta-asarone prevents
      autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice. 

PMID- 24457044
TI  - Losing faith and finding religion: religiosity over the life course and substance
      use and abuse.
AB  - BACKGROUND: Religion has only come into the light of scientific inquiry as a
      factor influencing health and behavior in the last few decades. While religiosity
      is a protective factor for contemporaneous substance misuse, the relationship
      between longitudinal changes in religiosity and substance use outcomes is
      understudied. METHODS: Using data from the National Comorbidity Study -
      Replication (N=6203), we examined how changes in religiosity from childhood to
      adulthood are related to use and abuse/dependence of licit (alcohol and tobacco)
      and illicit drugs. Multivariable logistic regression was used to account for
      potential confounders including demographic characteristics, familial disruption
      during childhood, and comorbid major depression. RESULTS: Religiosity was
      inversely associated with use and misuse of both licit and illicit substances;
      however this relationship varied by level of childhood religiosity. Relative to
      stable levels of religiosity from childhood to adulthood, a 2-unit decrease in
      religiosity from childhood was associated with increased likelihood of illicit
      drug use in the past year (odds ratio (OR): 2.43, 95% confidence interval (CI):
      1.39-4.25). However, a 2-unit increase in religiosity was also associated with
      past-year illicit drug use (OR: 1.85, 95% CI: 1.09-3.13). Comparable associations
      were found with a range of recent and lifetime measures of alcohol, tobacco, and
      illicit drugs. CONCLUSIONS: Substantial gains or losses in religiosity from
      childhood to adulthood are associated with substance use and misuse. Findings
      support the use of a life course approach to understanding the relationship
      between religiosity and substance use outcomes.

PMID- 24457045
TI  - Bioinformatics analysis of hemocyte miRNAs of scallop Chlamys farreri against
      acute viral necrobiotic virus (AVNV).
AB  - The sustainable development of the scallop Chlamys farreri industry in China is
      hindered by mass mortality mainly caused by a novel pathogen known as acute viral
      necrosis virus (AVNV). A better understanding of host-virus interactions,
      especially those at the molecular level, may facilitate the prevention and cure
      of AVNV infections. MicroRNAs (miRNAs) represent a class of small RNA molecules
      involved in several biological processes, including mediating host-pathogen
      responses. In this study, two hemocyte small RNA libraries were constructed from
      control (control library, CL) and AVNV-infected (infection library, IL) C.
      farreri for high throughput sequencing using Solexa technology. Acquired data
      were further used to identify conserved and novel miRNAs, screen differentially
      expressed miRNAs, and predict their target genes through bioinformatics analysis.
      Solexa sequencing produced 19,485,719 and 20,594,513 clean reads representing
      2,248,814 and 1,510,256 unique small RNAs from CL and IL, respectively. A total
      of 57 conserved miRNAs were identified in both libraries, among which only two
      were unique to IL. Novel miRNA prediction using the Crassostrea gigas genome as a
      reference revealed 11 candidate miRNAs, 10 of which were validated by RT-PCR.
      Differential expression (p < 0.001) between libraries was observed in 37 miRNAs,
      among which 30 and 7 miRNAs were up- and downregulated, respectively. Expression
      differences were further confirmed by qRT-PCR. A sequence homology search against
      available C. farreri ESTs showed that these differentially expressed miRNAs may
      target 177 genes involved in a broad range of biological processes including
      immune defense and stress response. This study is the first to characterize C.
      farreri miRNAs and miRNA expression profiles in response to AVNV infection by
      deep sequencing. The results presented here will deepen our understanding of the
      pathogenesis of AVNV at the molecular level and provide new insights into the
      molecular basis of host-pathogen interactions in C. farreri. 

PMID- 24457047
TI  - Reprint of "Pharmacokinetic modelling of the anti-malarial drug artesunate and
      its active metabolite dihydroartemisinin".
AB  - A four compartment mechanistic mathematical model is developed for the
      pharmacokinetics of the commonly used anti-malarial drug artesunate and its
      principle metabolite dihydroartemisinin following oral administration of
      artesunate. The model is structurally unidentifiable unless additional
      constraints are imposed. Combinations of mechanistically derived constraints are
      considered to assess their effects on structural identifiability and on model
      fits. Certain combinations of the constraints give rise to locally or globally
      identifiable model structures. Initial validation of the model under various
      combinations of the constraints leading to identifiable model structures was
      performed against a dataset of artesunate and dihydroartemisinin concentration
      time profiles of 19 malaria patients. When all the discussed constraints were
      imposed on the model, the resulting globally identifiable model structure was
      found to fit reasonably well to those patients with normal drug absorption
      profiles. However, there is wide variability in the fitted parameters and further
      investigation is warranted. 

PMID- 24457046
TI  - Inducible and coupled expression of the polyomavirus middle T antigen and Cre
      recombinase in transgenic mice: an in vivo model for synthetic viability in
      mammary tumour progression.
AB  - INTRODUCTION: Effective in vivo models of breast cancer are crucial for studying
      the development and progression of the disease in humans. We sought to engineer a
      novel mouse model of polyomavirus middle T antigen (PyV mT)-mediated mammary
      tumourigenesis in which inducible expression of this well-characterized viral
      oncoprotein is coupled to Cre recombinase (TetO-PyV mT-IRES-Cre recombinase or
      MIC). METHODS: MIC mice were crossed to the mouse mammary tumour virus (MMTV)
      reverse tetracycline transactivator (rtTA) strain to generate cohorts of virgin
      females carrying one or both transgenes. Experimental (rtTA/MIC) and control
      (rtTA or MIC) animals were administered 2 mg/mL doxycycline beginning as early as
      eight weeks of age and monitored for mammary tumour formation, in parallel with
      un-induced controls of the same genotypes. RESULTS: Of the rtTA/MIC virgin
      females studied, 90% developed mammary tumour with complete penetrance to all
      glands in response to doxycycline and a T50 of seven days post-induction, while
      induced or un-induced controls remained tumour-free after one year of induction.
      Histological analyses of rtTA/MIC mammary glands and tumour revealed that lesions
      followed the canonical stepwise progression of PyV mT tumourigenesis, from
      hyperplasia to mammary intraepithelial neoplasia/adenoma, carcinoma, and invasive
      carcinoma that metastasizes to the lung; at each of these stages expression of
      PyV mT and Cre recombinase transgenes was confirmed. Withdrawal of doxycycline
      from rtTA/MIC mice with end-stage mammary tumours led to rapid regression, yet
      animals eventually developed PyV mT-expressing and -non-expressing recurrent
      masses with varied tumour histopathologies. CONCLUSIONS: We have successfully
      created a temporally regulated mouse model of PyV mT-mediated mammary
      tumourigenesis that can be used to study Cre recombinase-mediated genetic changes
      simultaneously. While maintaining all of the hallmark features of the well
      established constitutive MMTV-PyV mT model, the utility of this strain derives
      from the linking of PyV mT and Cre recombinase transgenes; mammary epithelial
      cells are thereby forced to couple PyV mT expression with conditional ablation of
      a given gene. This transgenic mouse model will be an important research tool for
      identifying synthetic viable genetic events that enable PyV mT tumours to evolve
      in the absence of a key signaling pathway.

PMID- 24457048
TI  - Hospitalizations of nursing homes residents: the role of reimbursement policies.
AB  - Factors which contribute to hospitalization of nursing home residents are
      multiple and complex. They include dimensions of the policy setting as well as
      patient management practices. In seeking interventions to reduce such
      hospitalizations, most research has focussed on changing patient management. But
      provider reimbursement policies may also influence the decision to hospitalize
      nursing home residents. This includes payments to hospitals and general
      practitioners as well as to the nursing homes themselves. Differences in payment
      methods may mean that interventions that work well in one setting do not work
      well in another.This is a commentary on http://www.ijhpr.org/content/3/1/2/. 

PMID- 24457049
TI  - Claiming Darwin: Stephen Jay Gould in contests over evolutionary orthodoxy and
      public perception, 1977-2002.
AB  - This article analyzes the impact of the resurgence of American creationism in the
      early 1980s on debates within post-synthesis evolutionary biology. During this
      period, many evolutionists criticized Harvard biologist Stephen Jay Gould for
      publicizing his revisions to traditional Darwinian theory and opening evolution
      to criticism by creationists. Gould's theory of punctuated equilibrium was a
      significant source of contention in these disputes. Both he and his critics,
      including Richard Dawkins, claimed to be carrying the mantle of Darwinian
      evolution. By the end of the 1990s, the debate over which evolutionary thinkers
      were the rightful heirs to Darwin's evolutionary theory was also a conversation
      over whether Darwinism could be defended against creationists in the broader
      cultural context. Gould and others' claims to Darwin shaped the contours of a
      political, religious and scientific controversy. 

PMID- 24457050
TI  - Polychlorinated dioxins, furans (PCDD/Fs), and polychlorinated biphenyls (PCBs)
      and their trends in Canadian human milk from 1992 to 2005.
AB  - More than 300 samples of human milk were collected from individuals residing in
      various regions across Canada in the years 1992 to 2005. The milks were taken
      from the main populated areas east to west in southern Canada as well as from the
      region of Nunavik in northern Quebec and analysed for polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated
      biphenyls (PCBs). The concentrations, expressed in ng kg(-1) milk lipid, show an
      overall decrease of virtually all compounds examined including 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), World Health Organization 2005 toxic
      equivalents (WHO2005-TEQ) PCDD/PCDFs, WHO2005-TEQ dioxin-like PCBs (dl-PCBs), and
      total PCBs. Median values of 2,3,7,8-TCDD changed from about 1.5 ng kg(-1) milk
      lipid in 1992 to 0.8 ng kg(-1) in 2005 while the median WHO2005-TEQ PCDD/F fell
      from about 14-7 ng kg(-1) milk lipid in the same period. The concentrations of
      PCDD/Fs and PCBs in samples from Nunavik, which is in Arctic Quebec, were higher
      than those observed in milk from southern Quebec although this difference was not
      large. Over two time periods, milk samples from Hamilton, Ontario showed slightly
      higher levels of PCBs than Austin, Texas, USA--a North American city of similar
      size and development but with more than twice the PBDE exposure. When compared
      with earlier human milk data going back to the early 1980s, this large data set
      shows a steady decline of human exposure to POPs in Canada by a factor of about
      four times.

PMID- 24457051
TI  - Application of Fenton's reagent as a polishing step for removal of UV quenching
      organic constituents in biologically treated landfill leachates.
AB  - When landfill leachate, with or without biological pretreatment, is discharged to
      publically owned treatment works (POTWs), it can interfere with the installed
      treatment facilities. Biological treatment is ineffective for the removal of some
      of the bio-refractory organic matter, including UV254 quenching substances.
      Fenton's reagent treatment for biologically treated landfill leachates is
      examined in this study as a polishing step to make landfill leachates acceptable
      to POTWs. The optimum conditions for the Fenton's reagent treatment are explored.
      The molecular weight and hydrophobic-hydrophilic nature based fractions of the
      Fenton's treated leachate samples are analyzed to provide insight into the
      leachate fractions targeted by the Fenton's reagent. The results indicate that
      Fenton's reagent can act as a good compliment to biological treatment as it can
      remove leachate fractions which are widely considered to be bio-refractory. It
      exhibited good UV254 absorbance removal by removing larger molecular weight humic
      substances and thus, can help solve the UV254 quenching problem due to leachates
      discharged to POTWs.

PMID- 24457052
TI  - Remediation of polychlorinated biphenyl-contaminated soil by using a combination
      of ryegrass, arbuscular mycorrhizal fungi and earthworms.
AB  - In this work, a laboratory experiment was performed to investigate the influences
      of inoculation with the arbuscular mycorrhizal fungus (AMF) Glomus caledoniun L.
      and/or epigeic earthworms (Eisenia foetida) on phytoremediation of a PCB
      contaminated soil by ryegrass grown for 180d. Planting ryegrass, ryegrass
      inoculated with earthworms, ryegrass inoculated with AMF, and ryegrass co
      inoculated with AMF and earthworms decreased significantly initial soil PCB
      contents by 58.4%, 62.6%, 74.3%, and 79.5%, respectively. Inoculation with AMF
      and/or earthworms increased the yield of plants, and the accumulation of PCBs in
      ryegrass. However, PCB uptake by ryegrass accounted for a negligible portion of
      soil PCB removal. The number of soil PCB-degrading populations increased when
      ryegrass was inoculated with AMF and/or earthworms. The data show that fungal
      inoculation may significantly increase the remedial potential of ryegrass for
      soil contaminated with PCBs. 

PMID- 24457053
TI  - Bioturbation/bioirrigation by Chironomus plumosus as main factor controlling
      elemental remobilization from aquatic sediments?
AB  - Aquatic sediments represent a possibly significant sink of soluble inorganic
      elements/pollutants (metals, metalloids and rare earth elements) in ecosystems.
      Bioturbation/bioirrigation was shown to affect the remobilization of some
      elements where others seem to be unaffected. In view of these contrasting
      results, the effect of bioturbation/bioirrigation was examined using the
      invertebrate Chironomus plumosus in a laboratory experiment for a broad range
      (18) of elements. The experiments revealed an impact of invertebrate
      bioturbation/bioirrigation on elemental remobilization depending on chemical
      characteristics of the element ranging from strong influence to influence only at
      start when the larvae dig into the sediments. Three different types of
      remobilization were found: (i) element mobilization highly influenced by
      bioturbation/bioirrigation (DOC, N, Mg, Ca, Sr, Mo and U), (ii) strong element
      mobilization by bioturbation/bioirrigation at the start of the experiment when
      the larvae dig into the sediments and afterwards strong decrease, but to higher
      levels compared to values of treatments without invertebrate impact (Mn, Ni, As,
      Cd and Cs), and (iii) strong element mobilization by bioturbation/bioirrigation
      at start when the larvae dig into the sediments and afterwards strong decrease to
      levels found in treatments without invertebrate impact (Al, Fe, Co, Cu, Zn and
      Ce). During the experiment a distinct accumulation of most of the elements in C.
      plumosus was found, where they were not so much bound to the outer surface of C.
      plumosus but more within the gut system including food and feces. Hence,
      bioturbation/bioirrigation is certainly a main process controlling mobilization
      of elements from sediments. 

PMID- 24457054
TI  - Avoiding the formation of vesicles by patch excision from Xenopus oocytes.
AB  - BACKGROUND: The patch-clamp technique is well-established to investigate the
      function of ion channels. Several patch configurations have been described,
      including the inside-out patch configuration providing the unique advantage of
      having free access to the patch from the cytosolic side. An inside-out patch is
      predominantly built from a cell-attached patch by pulling the patch pipette back.
      However, when using pipettes with high resistance (>8 MOmega), often a vesicle is
      formed instead of the desired inside-out patch, preventing proper recording of
      ion currents. NEW METHOD: Using quartz pipettes with high resistance we studied
      the benefit of a simple alternative excision manoeuvre that significantly
      enhances the efficiency to obtain an inside-out patch from Xenopus oocytes.
      RESULTS: We show that the formation of vesicles depends on the direction of patch
      excision: after a cell-attached patch has formed, pushing the patch pipette first
      into the depth of the oocyte and exposing the patch only then to the bath
      solution generated a success rate of 89% (16 out of 18) for a proper inside-out
      patch, as evaluated by the current flowing through HCN2 channels which were
      heterologously expressed in the oocytes. COMPARISON WITH EXISTING METHOD: In
      contrast, with the same type of pipettes and oocytes only 22% (4 out of 18) of
      the patches developed HCN2 currents when pulling the pipette in the backward
      direction as usual. CONCLUSION: The difference in the success rate favours the
      idea to use "pushed inside-out patches" instead of "pulled inside-out patches"
      when studying ion channels expressed in Xenopus oocytes.

PMID- 24457055
TI  - Extraction of protein profiles from primary neurons using active contour models
      and wavelets.
AB  - The function of complex networks in the nervous system relies on the proper
      formation of neuronal contacts and their remodeling. To decipher the molecular
      mechanisms underlying these processes, it is essential to establish unbiased
      automated tools allowing the correlation of neurite morphology and the
      subcellular distribution of molecules by quantitative means. We developed
      NeuronAnalyzer2D, a plugin for ImageJ, which allows the extraction of neuronal
      cell morphologies from two dimensional high resolution images, and in particular
      their correlation with protein profiles determined by indirect immunostaining of
      primary neurons. The prominent feature of our approach is the ability to extract
      subcellular distributions of distinct biomolecules along neurites. To extract the
      complete areas of neurons, required for this analysis, we employ active contours
      with a new distance based energy. For locating the structural parts of neurons
      and various morphological parameters we adopt a wavelet based approach. The
      presented approach is able to extract distinctive profiles of several proteins
      and reports detailed morphology measurements on neurites. We compare the detected
      neurons from NeuronAnalyzer2D with those obtained by NeuriteTracer and Vaa3D
      Neuron, two popular tools for automatic neurite tracing. The distinctive profiles
      extracted for several proteins, for example, of the mRNA binding protein ZBP1,
      and a comparative evaluation of the neuron segmentation results proves the high
      quality of the quantitative data and proves its practical utility for biomedical
      analyses. 

PMID- 24457056
TI  - The effect of antiviral therapy on hepatitis C virus-related thrombocytopenia: a
      case report.
AB  - BACKGROUND: Autoimmune thrombocytopenic purpura is an immunological disorder
      characterized by increased platelet destruction due to presence of anti-platelet
      autoantibodies. Hepatitis C virus infection, which is one of the most common
      chronic viral infections worldwide, may cause secondary chronic immune
      thrombocytopenic purpura. CASE PRESENTATION: We report a case of a 51-year-old
      Caucasian female with hepatitis C virus infection who developed a severe,
      reversible, immune thrombocytopenia. Platelet count was as low as 56.000/mm3,
      hepatitis C virus serology was positive, serum glutamic oxaloacetic transaminase,
      serum glutamic pyruvic transaminase and gamma-glutamyltransferase serum levels
      were elevated. Disorders potentially associated with autoimmune thrombocytopenic
      purpura were ruled out. A corticosteroid treatment was started and led to an
      increase in platelet count. The patient was then treated with pegylated
      interferon alpha 2a and ribavirin. After four weeks of treatment hepatitis C
      virus - ribonucleic acid became undetectable and steroid treatment was
      discontinued. Six months of antiviral therapy achieved a sustained biochemical
      and virological response together with persistence of normal platelet count.
      CONCLUSION: In our case report hepatitis C virus seemed to play a pathogenic role
      in autoimmune thrombocytopenic purpura. Moreover, the successful response
      (negative hepatitis C virus - ribonucleic acid) to tapered steroids and antiviral
      therapy was useful to revert thrombocytopenia.

PMID- 24457058
TI  - Influence of low back pain on total knee arthroplasty outcome.
AB  - BACKGROUND: Preoperative pain and functional status are strong determinants of
      postsurgical success in total knee arthroplasty. Patients suffering chronic pain
      from other coexistent musculoskeletal problems may respond differently
      postoperatively, with potentially poorer outcomes after surgery. The aim of the
      study was to determine the influence of low back pain on the outcome of total
      knee replacement surgery. METHODS: All patients completed Oxford Knee Scores
      (OKS), American Knee Society Scores (AKSS) and SF-12 (both physical and mental
      components). Patients were divided into those with (n=40) and without a
      documented history of low back pain (n=305). RESULTS: OKS, AKSS and SF-12
      physical scores were significantly worse for patients with low back pain at 24
      months following surgery. The mental component of the SF-12 measure demonstrated
      a significant improvement in median mental health post-operatively for patients
      with no current history of low back pain. In contrast the group with low back
      pain showed no improvement in mental health scores post-operatively. CONCLUSION:
      This study demonstrates that symptomatic low back pain influences functional
      outcome after total knee arthroplasty surgery and that patients with low back
      pain show limited or no improvement in mental health post-operatively. Level of
      evidence II.

PMID- 24457057
TI  - A four-marker signature of TNF-RII, TGF-alpha, TIMP-1 and CRP is prognostic of
      worse survival in high-risk surgically resected melanoma.
AB  - BACKGROUND: E1694 tested GM2-KLH-QS21 vaccine versus high-dose interferon-alpha2b
      (HDI) as adjuvant therapy for operable stage IIB-III melanoma. We tested banked
      serum specimens from patients in the vaccine arm of E1694 for prognostic
      biomarkers. METHODS: Aushon Multiplex Platform was used to quantitate baseline
      serum levels of 115 analytes from 40 patients. Least absolute shrinkage and
      selection operator proportional hazard regression (Lasso PH) was used to select
      markers that are most informative for relapse-free survival (RFS) and overall
      survival (OS). Regular Cox PH models were then fit with the markers selected by
      the Lasso PH. Survival receiver operating characteristic (ROC) analysis was used
      to evaluate the ability of the models to predict 1-year RFS and 5-year OS.
      RESULTS: Four markers that include Tumor Necrosis Factor alpha Receptor II (TNF
      RII), Transforming Growth Factor alpha (TGF-alpha), Tissue Inhibitor of
      Metalloproteinases 1 (TIMP-1), and C-reactive protein (CRP) were found to be most
      informative for the prediction of OS (high levels correlate with worse
      prognosis). The dichotomized risk score based on the four markers could
      significantly separate the OS curves (p = 0.0005). When using the four-marker PH
      model to predict 5-year OS, we achieved an area under the curve (AUC) of 89%
      (cross validated AUC = 72%). High baseline TNF-RII was also significantly
      associated with worse RFS. The RFS with high (above median) TNF-RII was
      significantly lower than low TNF-RII (p = 0.01). CONCLUSIONS: The biomarker
      signature consisting of TNFR-II, TGF-alpha, TIMP-1 and CRP is significantly
      prognostic of survival in patients with high-risk melanoma and warrants further
      investigation.

PMID- 24457059
TI  - Adrenal cortical neoplasms: a study of clinicopathological features related to
      epidermal growth factor receptor gene status.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but highly malignant
      neoplasm with limited treatment options. METHODS: In this study, the
      clinicopathological features of 22 ACCs and 22 adrenocortical adenomas (ACA) were
      analyzed, and the EGFR protein expression, EGFR gene mutation status and EGFR
      gene copy number alteration of all tumors were examined using
      immunohistochemistry, fluorescence in situ hybridization (FISH), and the Scorpion
      Amplification Refractory Mutation System (ARMS), respectively. RESULTS: EGFR
      protein expression was detected in 63.6% of the ACC samples, and EGFR FISH was
      positive in 50% of the ACC samples (all were high polysomy on chromosome 7). In
      contrast, 27.3% of the ACA samples demonstrated EGFR expression, and none of the
      ACA samples tested positive by FISH. There were significant differences between
      the ACC and ACA in terms of protein expression (P = 0.035) and gene copy number
      alterations (P < 0.001). CONCLUSIONS: EGFR protein expression and high polysomy
      on chromosome 7 are frequent abnormalities in ACC than in ACA. VIRTUAL SLIDES:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2068470757103500.

PMID- 24457060
TI  - Comparison of rates of and charges from pregnancy complications in users of
      extended and cyclic combined oral contraceptive (COC) regimens: a brief report.
AB  - OBJECTIVE: To evaluate pregnancy complication rates and related charges in users
      of 84/7, 21/7 and 24/4 combined oral contraceptives (COCs). STUDY DESIGN: Data
      were obtained from the i3 InVision Data MartTM retrospective claims database.
      Subjects were aged 15-40 years, first prescribed a COC between 1/1/2006 and
      4/1/2011 and continuously insured for >=1 year. 84/7 users were matched 1:1 to
      21/7 and 24/4 users. RESULTS: Pregnancy-related complication rates and associated
      charges were significantly lower with 84/7 vs. 21/7 and 24/4 regimens.
      CONCLUSION: Preliminary data suggest 84/7 regimens may be associated with fewer
      pregnancy complications and lower related charges.

PMID- 24457061
TI  - Postplacental insertion of the levonorgestrel intrauterine device after cesarean
      delivery vs. delayed insertion: a randomized controlled trial.
AB  - OBJECTIVE: This trial was designed to compare levonorgestrel intrauterine device
      (LNG-IUD) use at 1 year after delivery between women randomized to postplacental
      insertion at the time of cesarean delivery and delayed insertion 4-8 weeks after
      delivery. STUDY DESIGN: This randomized controlled trial was conducted at two
      urban medical centers. Eligible pregnant women with planned cesarean deliveries
      were randomized to immediate postplacental insertion during cesarean or delayed
      insertion after 4-8 weeks. We used intention-to-treat analysis for the primary
      outcome of LNG-IUD use 12 months after delivery. RESULTS: Forty-two women were
      randomized, 20 into the postplacental group and 22 in the delayed group. Although
      confirmed use of the LNG-IUD 12 months after delivery was higher in the
      postplacental group (60.0% vs. 40.9%, p=.35), this difference was not
      statistically significance. Expulsion was significantly more common in the
      postplacental group (20.0% vs. 0%, p=.04). There were significant differences
      between the two sites in baseline population characteristics, follow-up and
      expulsion. The trial did not answer the intended question as it was halted early
      due to slow enrollment. CONCLUSIONS: Our results show higher expulsion after
      postplacental insertion compared to delayed insertion but suggest similar IUD use
      at 12 months. Moreover, it provides valuable lessons regarding a randomized
      controlled trial of postplacental LNG-IUD placement due to the challenges of
      estimating effect size and the nature of the population who might benefit from
      immediate insertion. IMPLICATIONS: Postplacental insertion of an IUD may improve
      use of highly effective contraception during the postpartum period. While our
      results suggest higher expulsion after postplacental insertion compared to
      delayed insertion and similar IUD use at 12 months, our trial was insufficient to
      definitively test our hypothesis.

PMID- 24457062
TI  - Predictors of adherence to hormonal contraceptives in a female veteran
      population.
AB  - OBJECTIVE: The objective was to identify predictors of adherence to hormonal
      contraceptives in a female veteran population. STUDY DESIGN: This was a
      retrospective cohort study of female veterans from the VA San Diego Healthcare
      System. The study period was April 1, 2010, to March 31, 2012. Each patient was
      followed for 1 year from the index date, defined as the date of first
      contraceptive prescription in the study time period. Adherence was defined as a
      medication possession ratio >= 0.9. Income was estimated using zip-code-based
      median household income and split into quintiles (quintile 1 being the lowest
      earning group). Logistic regression was used to analyze the association between
      adherence and the independent variables. RESULTS: A total of 805 patients were
      included in the final analysis. The majority of the population was white (62.2%)
      and receiving a 3-month supply of medication (87.6%). The following independent
      variables were predictive of increased adherence: 3-month supply versus 1-month
      supply [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.03-3.13], age group
      40-45 versus 18-24 (OR 2.57, 95% CI 1.16-5.70) and income quintiles 3 (OR 1.96,
      95% CI 1.16-3.29), 4 (OR 1.77, 95% CI 1.06-2.98) and 5 (OR 1.75, 95% CI 1.03
      2.98) each versus quintile 1 as reference group. The following were associated
      with decreased adherence: new start versus continuing user (OR 0.25, 95% CI 0.18
      0.37), OB/GYN provider versus primary care provider (OR 0.60, 95% CI 0.38-0.95),
      and highest weight group versus lowest weight group (OR 0.40, 95% CI 0.17-0.94).
      CONCLUSION: Hormonal contraceptive adherence in the veteran population is below
      optimal. Providing 3-month supplies of high-value therapies such as hormonal
      contraceptives is one strategy that may improve adherence. Initiatives to target
      lower socioeconomic status or new start populations to increase contraceptive
      adherence should also be considered. IMPLICATIONS: Adherence to hormonal
      contraceptives is not as well studied in the literature as some other high-value
      therapies. Identifying predictive variables for adherence may have implications
      for establishing possible interventions, or refining benefit structures, in order
      to increase adherence.

PMID- 24457063
TI  - The Society of Family Planning: closing in on our first decade and still going
      strong.

PMID- 24457064
TI  - Evaluation of the Nova StatStrip glucometer in a pediatric hospital setting.
AB  - CONTEXT: Routine point-of-care (POC) glucose monitoring in the pediatric setting
      has become increasingly important, both for assessing hypoglycemia as well as
      hyperglycemia. A reliable and precise system is required to monitor pediatric
      patients. OBJECTIVES: The aim of this study was to evaluate the Nova Biomedical
      StatStrip POC glucometer against the Roche ACCU-CHEK Inform in lieu of our
      currently used LifeScanSureStepFlexx POC glucose analyzer. DESIGN AND METHODS:
      Intra-assay and inter-assay precision, linearity, correlation and interference
      studies were performed as per the NCCLS criteria. An analysis of 37 pediatric
      samples across the linearity ranges of all the meters was used to assess
      concordance between the systems. RESULTS: The Nova StatStrip glucometer
      demonstrated an excellent coefficient of variation (<5%) for glucose across the
      entire analytical measurement range. The Nova StatStrip also had good concordance
      with the central laboratory (Bland-Altman plots r(2)=0.01), while Roche Inform
      had poorer correlation (Bland-Altman plots r(2)=0.46). We also evaluated the
      effect of hematocrit (20-60%) and maltose (100-500mg/dL) on the Nova StatStrip
      analyzer and demonstrated that there is little to no interference by either.
      CONCLUSIONS: The Nova StatStrip system gave the best performance with acceptable
      imprecision, good correlation, and minimal to no interference from hematocrit
      levels or maltose. The Nova StatStrip is a satisfactory replacement for our POC
      glucometer system and, additionally, provides results in less time (just 6 s)
      utilizing a lower amount of blood with the advantage of being immediately
      interfaced to our laboratory information systems.

PMID- 24457065
TI  - Association of serum phospholipid PUFAs with cardiometabolic risk: beneficial
      effect of DHA on the suppression of vascular proliferation/inflammation.
AB  - OBJECTIVES: Blood or dietary polyunsaturated fatty acids (PUFAs), particularly
      omega3-PUFAs were known for cardiovascular protective effect. However, the
      results are still controversial. We aimed to investigate the association of serum
      phospholipid PUFAs with cardiometabolic risk through cross-sectional/experimental
      studies. DESIGN/METHODS: Serum phospholipid FA compositions and cardiometabolic
      risk parameters were measured in controls [healthy: n=987, metabolic syndrome
      (MetS): n=214] and CAD patients (CAD-only: n=152, CAD+MetS: n=56). Experimental
      assays were performed in vascular smooth muscle cells (VSMCs). RESULTS: Major
      cardiometabolic risk markers, i.e. insulin resistance, hs-C-reactive proteins,
      and malondialdehyde were higher, and adiponectin and LDL particle size were lower
      in CAD patients, particularly those with MetS than in healthy controls. Serum
      linoleic acid (LA, C18:2omega-6) was lowest and dihomo-gamma-linolenic acids
      (DGLAs, C20:3omega-6) were highest in CAD patients with MetS among the 4 groups.
      Docosahexaenoic acid (DHA, C22:6omega-3) was lower and arachidonic acid (AA,
      C20:4omega-6) and omega6/omega3-PUFAs were higher in CAD patients than in
      controls. omega3-PUFAs were significantly lower in CAD patients, particularly
      those with MetS than in healthy controls. Multiple regression analysis revealed
      that AA and DHA among serum FAs were mainly associated with the cardiometabolic
      risk (beta'-coefficients for AA:0.336; DHA: -0.296) together with age, MetS
      factors, LA, DGLA and gender (r=0.529, p<0.001). Under LPS-induced stress
      condition, LA and DHA significantly suppressed VSMC proliferation. DHA also up
      regulated the phosphorylation of p38 and ERK, and dramatically inhibited nuclear
      translocation of NF-kappaB-p65 in VSMCs. CONCLUSION: AA and DHA were mainly
      associated with cardiometabolic risk. Particularly, DHA may be effective on
      suppression of vascular proliferation and inflammation.

PMID- 24457066
TI  - Ten leading causes of death in Taiwan: A comparison of two grouping lists.

PMID- 24457067
TI  - Almost winning: induced MEG theta power in insula and orbitofrontal cortex
      increases during gambling near-misses and is associated with BOLD signal and
      gambling severity.
AB  - In slot machine gambling, the "near-miss effect" (when a losing display
      physically resembles an actual win display) has been implicated in pathological
      gambling (PG). Functional magnetic resonance imaging (fMRI) with PG and non-PG
      participants shows that near-misses recruit reward-related circuitry, but little
      is known about the temporal dynamics and oscillatory changes underlying near
      misses. The present multi-modal imaging study investigated the near-miss effect
      by combining the spatial resolution of blood oxygen-level dependent (BOLD)-fMRI
      with the spatial and temporal resolution of magnetoencephalography (MEG) during a
      slot machine task in PG and non-PG groups. Given previous findings on outcome
      (win and near-miss) processing, functional overlap was hypothesized between
      induced changes in temporal oscillations and BOLD response to wins and near
      misses in PG. We first validated our task in a sample of varying gambling
      severity using BOLD-fMRI and then compared PG and non-PG participants using MEG
      to investigate changes in induced oscillatory power associated with win and near
      miss, relative to loss, outcomes. Across both modalities, near-misses recruited
      similar brain regions to wins, including right inferior frontal gyrus and insula.
      Using MEG, increased theta-band (4-7Hz) oscillations to near-misses were observed
      in the insula and right orbitofrontal cortex (OFC). Furthermore, this theta-band
      activity was positively associated with gambling severity. These findings
      demonstrate that the near-miss effect in insula and OFC is associated with
      induced theta oscillations. The significance of these findings for theories of PG
      and the development of potential biomarkers and therapeutic targets is discussed.

PMID- 24457069
TI  - Impact of dual mTORC1/2 mTOR kinase inhibitor AZD8055 on acquired endocrine
      resistance in breast cancer in vitro.
AB  - INTRODUCTION: Upregulation of PI3K/Akt/mTOR signalling in endocrine-resistant
      breast cancer (BC) has identified mTOR as an attractive target alongside anti
      hormones to control resistance. RAD001 (everolimus/Afinitor(r)), an allosteric
      mTOR inhibitor, is proving valuable in this setting; however, some patients are
      inherently refractory or relapse during treatment requiring alternative
      strategies. Here we evaluate the potential for novel dual mTORC1/2 mTOR kinase
      inhibitors, exemplified by AZD8055, by comparison with RAD001 in ER + endocrine
      resistant BC cells. METHODS: In vitro models of tamoxifen (TamR) or oestrogen
      deprivation resistance (MCF7-X) were treated with RAD001 or AZD8055 alone or
      combined with anti-hormone fulvestrant. Endpoints included growth, cell
      proliferation (Ki67), viability and migration, with PI3K/AKT/mTOR signalling
      impact monitored by Western blotting. Potential ER cross-talk was investigated by
      immunocytochemistry and RT-PCR. RESULTS: RAD001 was a poor growth inhibitor of
      MCF7-derived TamR and MCF7-X cells (IC50 >=1 MUM), rapidly inhibiting mTORC1 but
      not mTORC2/AKT signalling. In contrast AZD8055, which rapidly inhibited both
      mTORC1 and mTORC2/AKT activity, was a highly effective (P <0.001) growth
      inhibitor of TamR (IC50 18 nM) and MCF7-X (IC50 24 nM), and of a further T47D
      derived tamoxifen resistant model T47D-tamR (IC50 19 nM). AZD8055 significantly
      (P <0.05) inhibited resistant cell proliferation, increased cell death and
      reduced migration. Furthermore, dual treatment of TamR or MCF7-X cells with
      AZD8055 plus fulvestrant provided superior control of resistant growth versus
      either agent alone (P <0.05). Co-treating with AZD8055 alongside tamoxifen (P
      <0.01) or oestrogen deprivation (P <0.05) also effectively inhibited endocrine
      responsive MCF-7 cells. Although AZD8055 inhibited oestrogen receptor (ER) ser167
      phosphorylation in TamR and MCF7-X, it had no effect on ER ser118 activity or
      expression of several ER-regulated genes, suggesting the mTOR kinase inhibitor
      impact was largely ER-independent. The capacity of AZD8055 for ER-independent
      activity was further evidenced by growth inhibition (IC5018 and 20 nM) of two
      acquired fulvestrant resistant models lacking ER. CONCLUSIONS: This is the first
      report demonstrating dual mTORC1/2 mTOR kinase inhibitors have potential to
      control acquired endocrine resistant BC, even under conditions where everolimus
      fails. Such inhibitors may prove of particular benefit when used alongside anti
      hormonal treatment as second-line therapy in endocrine resistant disease, and
      also potentially alongside anti-hormones during the earlier endocrine responsive
      phase to hinder development of resistance.

PMID- 24457071
TI  - Differential expression of cro, the lysogenic cycle repressor determinant of
      bacteriophage A2, in Lactobacillus casei and Escherichia coli.
AB  - Expression of bacteriophage A2-encoded cro in Escherichia coli gives rise to two
      co-linear polypeptides, Cro and Cro*, which were proposed to form a regulatory
      tandem to modulate the frequency with which the phage would choose between the
      lytic and the lysogenic cycles. In this communication, it is reported that Cro is
      the canonical product of the gene cro while Cro* results from a -1 ribosome
      frameshift during translation and is twelve amino acids shorter than Cro.
      However, frameshifting was not observed during phage development in Lactobacillus
      casei. Furthermore, wild type phages and cro-frameshifting negative mutants
      present the same phenotype, thus corroborating that only the canonical form of
      Cro is needed to produce a viable phage progeny. 

PMID- 24457070
TI  - Visualization of intracellular pathways of engineered baculovirus in mammalian
      cells.
AB  - Baculoviruses are a promising gene delivery vector. They have the ability to
      express large transgenes in mammalian cells without displaying pathogenicity in
      humans; however, little is known about their transduction mechanisms in target
      cells. In this study, we use colocalization and live-cell imaging studies to
      elucidate the internalization and intracellular trafficking pathways of
      baculoviruses through direct visualization of VP39-GFP-labeled viral particles
      and various endocytic structures within target cells. Drug inhibition and
      confocal microscopy results suggested that baculoviruses enter the cells via
      clathrin-mediated endocytosis in a dynamin-dependent manner. Viral particles were
      shown to traffic through early endosomes, triggering a low-pH-dependent endosomal
      fusion process of viruses. Suppressed autophagy activity enhanced viral
      transduction and overexpression of autophagosomes reduced viral transduction,
      suggesting that autophagy is involved in degradation process of viral particles.
      Actin filaments were involved in the viral transduction, while microtubules
      negatively regulated viral transduction by facilitating the fusion of
      autophagosomes with lysosomes to form autolysosomes, where degradation of viral
      particles occurs. These results shed some light on the essential cellular factors
      limiting viral transduction, which can be used to improve the use of baculoviral
      vectors in cell and gene therapy. 

PMID- 24457072
TI  - Immunogenicity of different recombinant rabbit hemorrhagic disease virus-like
      particles carrying CD8+ T cell epitope from chicken ovalbumin (OVA).
AB  - To explore the capacity and immunogenicity of virus-like particles (VLPs) of
      rabbit hemorrhagic disease virus (RHDV) accommodating foreign amino acid
      sequences, integrations were performed at the following four locations of the
      structural protein VP60 of RHDV using the OVA257-264 CD8+ T cell epitope
      (SIINFEKL): (1) inserting at the N-terminus of the VP60 protein (N1); (2)
      replacing amino acid positions 2-14 of the VP60 protein (N2); (3) replacing amino
      acid positions 196-207 of the VP60 protein (I1); and (4) replacing amino acid
      positions 217-228 of the VP60 protein (I2). The recombinant proteins were
      expressed by baculovirus expression system. The ability to form RHDV-like
      particles was confirmed by electron microscopy. The immunogenicity of the four
      recombinant proteins (N1, N2, I1 and I2) was evaluated in mice without any
      adjuvants. The results indicated that the four recombinant proteins (N1, N2, I1
      and I2) could assemble into VLPs. All of the recombinant proteins could induce a
      specific immune response. Recombinant proteins I1 and I2 were able to elicit both
      high levels of IFN-gamma secretion and anti-VP60 specific immune responses in the
      murine model. The levels of the VP60-specific IgG antibody in groups I1 and I2
      displayed higher optical density (OD) values than those of groups N1 and N2
      (P<0.001, P<0.001). The number of IFN-gamma-producing splenocytes in mice that
      were immunized with recombinant proteins I1 and I2 was also significantly greater
      compared with mice that were immunized with recombinant proteins N1 and N2
      (P<0.01). All of these above mentioned results might be beneficial to the
      establishment of the RHDV-VLPs display system. 

PMID- 24457073
TI  - A possible scenario for the evolution of Banana streak virus in banana.
AB  - Outbreaks of Banana streak virus (BSV) have been recorded worldwide where Musa
      spp. is grown during the last 20 years with no convincing evidence of epidemics.
      Epidemics were previously reported in Uganda where BSV is currently endemic. BSV
      is a plant pararetrovirus of the family Caulimoviridae, genus Badnavirus it
      causes chlorosis leaf streak disease. The information currently available on
      banana streak disease makes it possible to identify a complex of distinct BSV
      species each causing the same disease. BSV exists in two states: one as an
      episomal form, infecting plant cells; the other as viral DNA integrated within
      the B genome of banana (endogenous BSV-eBSV) forming a viral genome for de novo
      viral particles. Both forms can be infectious in banana plants. The BSV phylogeny
      is polyphyletic with BSV distributed in two clades. Clade 1 clusters BSV species
      that occur worldwide and may have an eBSV counterpart, whereas Clade 3 only
      comprises BSV species from Uganda. Clearly, two distinct origins explain such BSV
      diversity. However, the epidemiology/outbreaks of BSV remains unclear and the
      role of eBSV needs to be clarified. In this review, the biodiversity of BSV is
      explained and discussed in the light of field and molecular epidemiology data. A
      scheme is proposed for the co-evolution of BSV and banana based on old or recent
      infection hypotheses related to African domestication sites and banana
      dissemination to explain the disease context.

PMID- 24457074
TI  - The prevalence of badnaviruses in West African yams (Dioscorea cayenensis
      rotundata) and evidence of endogenous pararetrovirus sequences in their genomes.
AB  - Yam (Dioscorea spp.) is an important vegetatively-propagated staple crop in West
      Africa. Viruses are pervasive in yam worldwide, decreasing growth and yield, as
      well as hindering the international movement of germplasm. Badnaviruses have been
      reported to be the most prevalent in yam, and genomes of some other badnaviruses
      are known to be integrated in their host plant species. However, it was not clear
      if a similar scenario occurs in Dioscorea yam. This study was conducted to verify
      the prevalence of badnaviruses, and determine if badnavirus genomes are
      integrated in the yam genome. Leaf samples (n=58) representing eight species of
      yam from global yam collections kept at CIRAD, France, and 127 samples of D.
      rotundata breeding lines (n=112) and landraces (n=15) at IITA, Nigeria, were
      screened using generic badnavirus PCR primers. Positive amplification of an
      expected ca. 579bp fragment, corresponding to a partial RT-RNaseH region, was
      detected in 47 (81%) of 58 samples analysed from CIRAD collections, and 100% of
      the 127 IITA D. rotundata samples. All the D. cayenensis and D. rotundata samples
      from the CIRAD and IITA collections tested PCR-positive, and sequencing of a
      selection of the PCR products confirmed they were typical of the genus
      Badnavirus. A comparison of serological and nucleic acid techniques was used to
      investigate whether the PCR-positives were sequences amplified from badnavirus
      particles or putative endogenous badnavirus sequences in the yam genome. Protein
      A sandwich-enzyme-linked immunosorbent assay (PAS-ELISA) with badnavirus
      polyclonal antisera detected cross-reacting viral particles in only 60% (92 of
      153) of the CIRAD collection samples analysed, in contrast to the aforementioned
      81% by PCR. Immunosorbent electron microscopy (ISEM) of virus preparations of a
      select set of 16 samples, representing different combinations of positive and
      negative PCR and PAS-ELISA results, identified bacilliform particles in 11 of
      these samples. Three PCR-positive yam samples from Burkina Faso (cv. Pilimpikou)
      were identified in which no viral particles were detected by either PAS-ELISA or
      ISEM. Southern hybridisation results using a yam badnavirus RT-RNaseH sequence
      (Gn155Dr) as probe, supported a lack of badnavirus particles in the cv.
      Pilimpikou and identified their equivalent sequences to be of plant genome
      origin. Probe Gn155Dr, however, hybridised to viral particles and plant genomic
      DNA in three D. rotundata samples from Guinea. These results represent the first
      data demonstrating the presence of integrated sequences of badnaviruses in yam.
      The implications of this for virus-indexing, breeding and multiplication of seed
      yams are discussed.

PMID- 24457075
TI  - Optimal protocol for PTEN immunostaining; role of analytical and preanalytical
      variables in PTEN staining in normal and neoplastic endometrial, breast, and
      prostatic tissues.
AB  - In some tumors, phosphatase and tensin homolog (PTEN) inactivation may have
      prognostic importance and predictive value for targeted therapies.
      Immunohistochemistry (IHC) may be an effective method to demonstrate PTEN loss.
      It was claimed that PTEN IHC showed poor reproducibility, lack of
      standardization, and variable effects of preanalytical factors. In this study, we
      developed an optimal protocol for PTEN IHC, with clone 6H2.1, by checking the
      relevance of analytical variables in normal tissue and tumors of endometrium,
      breast, and prostate. Pattern and intensity of cellular staining and background
      nonspecific staining were quantified and subjected to statistical analysis by
      linear mixed models. The proposed protocol showed a statistically best
      performance (P < .05) and included a high target retrieval solution, 1:100
      primary antibody dilution (2.925 mg/L), FLEX diluent, and EnVisionFLEX+ detection
      method, with a sensitivity and specificity of 72.33% and 78.57%, respectively.
      Staining specificity was confirmed in cell lines and animal models. Endometrial
      carcinomas with PTEN genetic abnormalities showed statistically lower staining
      than tumors without alterations (mean histoscores, 34.66 and 119.28,
      respectively; P = .01). Controlled preanalytical factors (delayed fixation and
      overfixation) did not show any statistically significant effect on staining with
      optimal protocol (P > .001). However, there was a trend of significance for
      decreased staining and fixation under high temperature. Moreover, staining was
      better in endometrial aspirates than in matched hysterectomy specimens, subjected
      to less controlled preanalytical variables (mean histoscores, 80 and 40,
      respectively; P = .002). A scoring system combining intensity of staining and
      percentage of positive cells was statistically associated with PTEN alterations
      (P = .01). 

PMID- 24457076
TI  - Intercellular adhesion molecule 1/2 and E-selectin in plasma cell mastitis:
      immunohistochemical study of 35 cases.
AB  - Plasma cell mastitis (PCM) is one of the most frequently encountered inflammatory
      diseases of the nonlactating breast. Histologically, PCM is characterized by
      infiltration of relatively abundant plasma cells into the mammary ducts. Its
      pathogenesis has remained unknown. In this study, we immunolocalized
      intercellular adhesion molecule (ICAM) 1 and 2 and E-selectin, all of which play
      pivotal roles in the inflammatory process, in 35 cases of PCM. We then compared
      the results with those of non-PCM and nonpathologic breast tissue. In the ductal
      epithelium, ICAM-1 immunoreactivity was significantly more pronounced in PCM than
      in non-PCM (P = .045). Both ICAM-1 (P < .001) and ICAM-2 (P = .001) were
      significantly more pronounced in PCM than in nonpathologic breast tissue.
      However, no significant differences in ICAM-2 and E-selectin immunoreactivity
      were detected between ductal epithelium of PCM and non-PCM. ICAM-1, but not ICAM
      2 or E-selectin, demonstrated significantly higher immunoreactivity in
      endothelial cells of PCM than in nonpathologic breast (P < .001). These results
      all suggest that ICAM-1 in both ductal epithelium and endothelium plays important
      roles in the inflammatory process of PCM, possibly through margination,
      extravasation, and attachment of plasma cells and lymphocytes, which may result
      in continuous inflammatory cell homing to ductal epithelial cells. 

PMID- 24457077
TI  - c-JUN N-terminal kinase (JNK) is activated and contributes to tumor cell
      proliferation in classical Hodgkin lymphoma.
AB  - c-JUN N-terminal Kinase (JNK) is activated/phosphorylated by upstream MAPK
      kinases (MKK), and, in turn, phosphorylates and activates its major substrate c
      JUN, a member of the activator protein-1 (AP-1) transcription factors. c-JUN is
      overexpressed and activated in Hodgkin and Reed Sternberg cells (HRS) of
      classical Hodgkin lymphoma (cHL), however, the mechanism of its activation
      remains unknown. JNK activation was immunohistochemically assessed in 60 cases of
      HL and in a control group of 151 B-cell non-Hodgkin lymphomas. The biologic
      effects of JNK activation in cultured HRS cells were investigated using colony
      formation, cell growth and viability assays and cell cycle analysis by flow
      cytometry. Western blotting was used to assess protein levels. p-JNK was
      expressed in 90% of HL, 83% of Burkitt lymphomas, 28% of mantle cell lymphomas,
      23% of diffuse large B-cell lymphomas, 19% of follicular lymphomas, and 18% of
      extranodal marginal zone lymphomas of MALT type. None of the 48 cases of chronic
      lymphocytic leukemia/small lymphocytic lymphoma and 18 cases of plasma cell
      myeloma showed JNK phosphorylation (P < 001, Kruskall-Wallis test).
      Pharmacological inhibition of JNK activity in cultured HRS cells resulted in a
      significant decrease of cell growth, which was associated with cell cycle arrest
      at the G2/M phase. The cell cycle effects were linked to deactivation of c-JUN
      and upregulation of its known target, the cyclin-dependent kinase inhibitor p21.
      JNK is highly activated in HRS cells, and may contribute to uncontrolled cell
      cycle progression and proliferation of tumor cells in cHL. 

PMID- 24457078
TI  - Embryonal tumors with ependymoblastic rosettes--reply.

PMID- 24457079
TI  - Rhabdoid glioblastoma is distinguishable from classical glioblastoma by
      cytogenetics and molecular genetics.
AB  - The clinicopathologic and molecular genetic features of 5 cases of rhabdoid
      glioblastoma, an extremely rare variant of glioblastoma that tends to affect
      patients at a young age, were investigated by immunohistochemical analysis and
      focused molecular genetic studies including array-based comparative genomic
      hybridization. All 5 cases had supratentorial tumors that immunohistochemical
      analysis revealed to be robustly positive for epithelial membrane antigen,
      vimentin, p53, and PDGFRalpha (platelet-derived growth factor receptor, alpha
      polypeptide) but only focally positive for glial fibrillary acidic protein.
      Although complete retention of SMARCB1 (INI1) was observed in all 5 cases,
      epidermal growth factor receptor (EGFR) amplification, PTEN (phosphatase and
      tensin homolog) loss, homozygous deletion of cyclin-dependent kinase inhibitor
      2A, 1p/19q codeletion, and isocitrate dehydrogenase 1 R132/IDH2 R172 mutation
      were not observed in any case, although a high level of EGFR polysomy was
      detected in 1 recurrent tumor. Although c-MET (MET protein) expression was focal
      but robustly positive in 3 cases, met proto-oncogene (MET) fluorescence in situ
      hybridization revealed low polysomy but not MET amplification. MGMT (O-6
      methylguanine-DNA methyl-40 transferase) methylation-specific polymerase chain
      reaction revealed MGMT methylation in only 1 case. Furthermore, array-based
      comparative genomic hybridization revealed gain of chromosome 7 and loss of 1p,
      6, 8p, 11, 13q, and 18q but no deletion of chromosome 22. In contrast to the
      classical subtype of primary glioblastoma, the cases studied here were
      characterized by the absence of EGFR amplification, PTEN loss, and 9p homozygous
      deletion and overexpression of p53, PDGFRalpha, and c-MET, suggesting that they
      can be classified as the proneural or mesenchymal subtype of glioblastoma and
      benefit from intensive therapy that includes temozolomide. 

PMID- 24457080
TI  - Systemic lupus erythematosus-associated neutrophilic dermatosis--an
      underrecognized neutrophilic dermatosis in patients with systemic lupus
      erythematosus.
AB  - Neutrophilic dermatoses are an uncommon manifestation of lupus. We describe the
      clinical and histopathologic features of 14 patients with systemic lupus
      erythematosus (SLE) and neutrophilic dermatoses, 2 of whom had no prior history
      of SLE. Thirteen patients were female, ranging in age from 27 to 62 years (mean
      age, 42.8 years). One patient was a 20-year-old man. Most lesions were described
      as erythematous papules and plaques and showed annular morphology in 6 patients
      and a photodistribution in 2 patients. Histopathologic examination in all cases
      showed an interstitial neutrophilic infiltrate with leukocytoclasis that ranged
      from sparse in 5 cases and moderate to dense in 9 cases. With one exception,
      those cases with moderate to dense infiltrates resembled Sweet's syndrome at
      scanning magnification. Two cases resembled bullous SLE, and 1 case showed
      overlapping features of bullous SLE and Sweet's syndrome. Interface changes were
      seen in 8 patients, which were subtle and vacuolar in 7. One case was associated
      with a florid interface tissue reaction. Dermal mucin was seen in 4 cases and was
      a prominent feature in only one of these. One case showed a minute discrete focus
      resembling palisaded neutrophilic and granulomatous dermatitis. It is important
      to consider SLE-associated neutrophilic dermatosis in the differential diagnosis
      of neutrophilic tissue reactions particularly because some patients will have no
      prior history of lupus. It is also important to be aware of the broad histologic
      spectrum that may be encountered in SLE-associated neutrophilic dermatosis,
      ranging from subtle paucicellular lesions to florid Sweet's-like lesions
      associated with a dense neutrophilic infiltrate. 

PMID- 24457081
TI  - Pancreatic ductal adenocarcinoma with autoimmune pancreatitis-like histologic and
      immunohistochemical features.
AB  - Autoimmune pancreatitis (AIP) often manifests as a mass lesion causing
      obstructive jaundice, clinically mimicking pancreatic carcinoma. A diagnosis of
      AIP may obviate the need for surgical resection, as most patients respond to
      steroid treatment. However, it is not clear whether these 2 conditions can
      coexist. In this study, 105 specimens resected for pancreatic ductal
      adenocarcinoma (PDAC) that also have changes of chronic pancreatitis were
      examined for features considered to be characteristic of AIP. Of 105 cases of
      PDAC with changes of chronic pancreatitis, 10 (9.5%) exhibited histologic
      features of AIP, including exuberant fibrosis, lymphoplasmacytic infiltration,
      obliterative phlebitis, or granulocytic epithelial lesions. Of these 10 cases, 7
      had more than 20 immunoglobulin G4+ plasma cells per high-power field. Of these 7
      cases, 5 were analyzed for Kirsten rat sarcoma viral oncogene mutation and SMAD4
      expression. Three cases showed K-ras mutation and/or loss of SMAD4 expression in
      benign AIP-like areas. These findings suggest 2 possibilities: first, AIP-like
      lesions may occur in a small but significant portion of PDAC cases; second, some
      PDACs may arise in a background of AIP. Therefore, caution is necessary when
      making a diagnosis of AIP by needle biopsy of a mass lesion, and patients with a
      tentative AIP diagnosis should be closely followed up clinically. 

PMID- 24457082
TI  - Embryonal tumors with ependymoblastic rosettes.

PMID- 24457083
TI  - Diagnostic utility of MYC amplification and anti-MYC immunohistochemistry in
      atypical vascular lesions, primary or radiation-induced mammary angiosarcomas,
      and primary angiosarcomas of other sites.
AB  - Breast cancer patients who receive radiation therapy or develop chronic
      lymphedema following axillary dissection can develop secondary mammary
      angiosarcomas (ASs) and, additionally, atypical vascular lesions (AVLs) in the
      former group. Recently, MYC amplification by fluorescence in situ hybridization
      (FISH) has been identified in secondary mammary AS but not in AVL and most
      primary mammary AS as well as AS of other sites. We studied MYC amplification and
      MYC protein expression in 7 radiation-induced AVLs, 9 secondary mammary ASs, 17
      primary mammary ASs, and 20 primary ASs of other sites by FISH analysis and
      immunohistochemistry. All 9 secondary mammary ASs showed gene amplification and
      protein expression, whereas neither was found in any of 7 AVLs. No MYC
      amplification or protein expression was identified in any of the 17 primary
      mammary ASs. Among primary ASs of other sites, 1 cardiac AS and 1 skin AS showed
      gene amplification and protein expression. The remaining 18 did not show
      amplification (90%), but some demonstrated protein expression (39%). We conclude
      that MYC amplification by FISH is present in secondary mammary AS but not in AVL.
      We also found MYC amplification in 1 primary skin AS and 1 primary cardiac AS.
      There was 100% concordance between MYC amplification and protein expression in
      all AVL, primary mammary AS, and secondary mammary AS, whereas only 65%
      concordance was found in AS of other sites. MYC protein expression in AS can be
      helpful in certain diagnostic scenarios in the breast but not in other sites. 

PMID- 24457084
TI  - Genomic variability of monkeypox virus among humans, Democratic Republic of the
      Congo.
AB  - Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active
      disease surveillance has assessed monkeypox disease prevalence and geographic
      range, information about virus diversity is lacking. We therefore assessed genome
      diversity of viruses in 60 samples obtained from humans with primary and
      secondary cases of infection from 2005 through 2007. We detected 4 distinct
      lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that
      seemed to correlate with human-to-human transmission (p = 0.0544). The data
      suggest a high frequency of spillover events from the pool of viruses in nonhuman
      animals, active selection through genomic destabilization and gene loss, and
      increased disease transmissibility and severity. The potential for accelerated
      adaptation to humans should be monitored through improved surveillance. 

PMID- 24457085
TI  - Distribution and habitat characterization of the recently introduced invasive
      mosquito Aedes koreicus [Hulecoeteomyia koreica], a new potential vector and pest
      in north-eastern Italy.
AB  - BACKGROUND: The container breeding species belonging to the genus Aedes (Meigen)
      are frequently recorded out of their place of origin. Invasive Aedes species are
      proven or potential vectors of important Arboviruses and their establishment in
      new areas pose a threat for human and animal health. A new species of exotic
      mosquito was recorded in 2011 in north-eastern Italy: Aedes (Finlaya) koreicus
      [Hulecoeteomyia koreica]. The aim of this study was to characterize the biology,
      the environment and the current distribution of this mosquito in north-eastern
      Italy. Morphological details useful to discriminate this species from other
      invasive Aedes mosquitoes are also given (see Additional files). METHODS: All
      possible breeding sites for larval development were monitored. In addition,
      ovitraps and traps for adults were used to collect eggs and adults. The
      mosquitoes (larvae and adults) were identified morphologically and molecularly.
      Environmental data and climatic variables during the period of mosquito activity
      (from April to October) were considered. RESULTS: Aedes koreicus was found in 37
      municipalities (39.4%) and was detected in 40.2% of places and in 37.3% of larval
      habitats monitored, in a range of altitude from 173 to 1250 m.a.s.l.. Garden
      centres were the most common locations (66.7%), followed by streets/squares
      (57.1%), private gardens (46.4%) and cemeteries (21.1%) (p < 0.01). The main
      larval habitats were catch basins (48.5%) and artificial water containers
      (41.8%). As for Aedes albopictus [Stegomyia albopicta], ovitraps were attractive
      for adult females resulting in the higher rate of positivity (15/21; 71.4%) among
      breeding sites. The period of Ae. koreicus activity ranged from March 29 to
      October 29. CONCLUSION: The species is clearly established in the area and is now
      overlapping with other vectors such as Ae. albopictus and colonizing areas over
      800 m.a.s.l, not yet or sporadically reached by the tiger mosquito. The data
      collected are essential to assess the risk of colonization of other parts of
      Italy and Europe, as well as the risk of spreading of pathogens transmitted.
      These findings stress the importance of implementing entomological surveillance
      for early detection of invasive species, which is necessary for eradication or
      limitation of its further spread.

PMID- 24457086
TI  - Distal rhythm influences whether or not listeners hear a word in continuous
      speech: support for a perceptual grouping hypothesis.
AB  - Due to extensive variability in the phonetic realizations of words, there may be
      few or no proximal spectro-temporal cues that identify a word's onset or even its
      presence. Dilley and Pitt (2010) showed that the rate of context speech, distal
      from a to-be-recognized word, can have a sizeable effect on whether or not a word
      is perceived. This investigation considered whether there is a distinct role for
      distal rhythm in the disappearing word effect. Listeners heard sentences that had
      a grammatical interpretation with or without a critical function word (FW) and
      transcribed what they heard (e.g., are in Jill got quite mad when she heard there
      are birds can be removed and Jill got quite mad when she heard their birds is
      still grammatical). Consistent with a perceptual grouping hypothesis,
      participants were more likely to report critical FWs when distal rhythm
      (repeating ternary or binary pitch patterns) matched the rhythm in the FW
      containing region than when it did not. Notably, effects of distal rhythm and
      distal rate were additive. Results demonstrate a novel effect of distal rhythm on
      the amount of lexical material listeners hear, highlighting the importance of
      distal timing information and providing new constraints for models of spoken word
      recognition. 

PMID- 24457088
TI  - Design and synthesis of N1-aryl-benzimidazoles 2-substituted as novel HIV-1 non
      nucleoside reverse transcriptase inhibitors.
AB  - A series of novel N1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and
      evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of
      them proved to be effective in inhibiting HIV-1 replication at submicromolar and
      nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs),
      with low cytotoxicity. The preliminary structure-activity relationship (SAR) of
      these new derivatives was discussed and rationalized by docking studies. 

PMID- 24457087
TI  - Significance of ERbeta expression in different molecular subtypes of breast
      cancer.
AB  - PURPOSE: This study is to investigate the estrogen receptor beta (ERbeta)
      expression in molecular subtypes of breast cancer and clinic significance of
      ERbeta expression. METHOD: The ERbeta expression was detected in 730 cases of
      breast cancer tissue specimens by immunohistochemistry. Twenty-one patients were
      censored during 2-10 years follow-up. The difference in ERbeta expression was
      analyzed by Pearson Chi-square Test. Its correlation with estrogen receptor alpha
      (ERalpha), progesterone receptor (PR) and human epidermal growth factor receptor
      2 (Her-2) was analyzed by Spearman rank correlation. The accumulative tumor-free
      survival rate was calculated by Kaplan-Meier method and difference in survival
      rate was analyzed by Log-rank test. Cox regression was used for multi-factor
      analysis. RESULT: The ERbeta expression was significantly different among the
      molecular subtypes of breast cancer (P < 0.05). The ERbeta expression in breast
      cancer was positively correlated with Her-2 (P < 0.05) while it had no
      correlation with ERalpha and Her-2. The expression of ERalpha was negatively
      correlated with Her-2 (P < 0.01) whereas positively correlated with PR (P <
      0.01). The expression of PR was negatively correlated with Her-2 (P < 0.05). The
      tumor-free survival rate in patients with positive ERbeta expression was
      significantly lower than that in patients with negative ERbeta expression.
      CONCLUSION: Positive ERbeta expression is a poor prognostic factor of breast
      cancer. VIRTUAL SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1084557586106833.

PMID- 24457090
TI  - Synthesis and biological evaluation of all eight stereoisomers of DPP-IV
      inhibitor saxagliptin.
AB  - All eight stereoisomers of saxagliptin have been synthesized and evaluated for
      their inhibitory activity against DPP-IV. It was unambiguously confirmed that the
      configuration of saxagliptin was critical to potent inhibition of DPP-IV. Docking
      study was performed to elucidate the configuration-activity relationship of
      saxagliptin stereoisomers. Tyr662 and Tyr470 have been suggested as the key
      residues of DPP-IV interacting with the inhibitors. This work provides valuable
      information for further inhibitor design against DPP-IV. 

PMID- 24457089
TI  - 3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo
      resistant cancer cells.
AB  - Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical
      treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive
      as corresponding regular cancer cells under the exposure to anticancer ceramide
      analogs. In this work we designed five new ceramide analogs with different
      backbones, in order to test the hypothesis that extending the conjugated system
      in ceramide analogs would lead to an increase of their anticancer activity and
      selectivity towards resistant cancer cells. The analogs with the 3-ketone-4,6
      diene backbone show the highest apoptosis-inducing efficacy. The most potent
      compound, analog 406, possesses higher pro-apoptotic activity in chemo-resistant
      cell lines MCF-7TN-R and NCI/ADR-RES than the corresponding chemo-sensitive cell
      lines MCF-7 and OVCAR-8, respectively. However, this compound shows the same
      potency in inhibiting the growth of another pair of chemo-sensitive and chemo
      resistant cancer cells, MCF-7 and MCF-7/Dox. Mechanism investigations indicate
      that analog 406 can induce apoptosis in chemo-resistant cancer cells through the
      mitochondrial pathway. Cellular glucosylceramide synthase assay shows that analog
      406 does not interrupt glucosylceramide synthase in chemo-resistant cancer cell
      NCI/ADR-RES. These findings suggest that due to certain intrinsic properties,
      ceramide analogs' pro-apoptotic activity is not disrupted by the normal drug
      resistance mechanisms, leading to their potential use for overcoming cancer
      multidrug-resistance. 

PMID- 24457092
TI  - Design, synthesis and biological evaluation of negatively charged 111In-DTPA
      octreotide derivatives.
AB  - Our previous studies indicated that (111)In-diethylenetriaminepentaacetic acid
      ((111)In-DTPA)-octreotide derivatives with an additional negative charge by
      replacing N-terminal d-phenylalanine (d-Phe) with an acidic amino acid such as l
      aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels
      when compared with (111)In-DTPA-D-Phe(1)-octreotide. On the basis of the
      findings, we designed, synthesized and evaluated two Asp-modified (111)In-DTPA
      conjugated octreotide derivatives, (111)In-DTPA-Asp(1)-octreotide and (111)In
      DTPA-Asp(0)-D-Phe(1)-octreotide. While (111)In-DTPA-Asp(1)-octreotide showed
      negligible AR42J cell uptake, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited
      AR42J cell uptake similar to that of (111)In-DTPA-D-Phe(1)-octreotide. When
      administered to AR42J tumor-bearing mice, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide
      exhibited renal radioactivity levels significantly lower than did (111)In-DTPA-D
      Phe(1)-octreotide at 1 and 3 h post-injection. No significant differences were
      observed in tumor accumulation between (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide
      and (111)In-DTPA-D-Phe(1)-octreotide after 1 and 3h injection. The findings in
      this study suggested that an interposition of an Asp at an appropriate position
      in (111)In-DTPA-D-Phe(1)-octreotide would constitute a useful strategy to develop
      (111)In-DTPA-D-Phe(1)-octreotide derivatives of low renal radioactivity levels
      while preserving tumor accumulation.

PMID- 24457091
TI  - Degrasyn-like symmetrical compounds: possible therapeutic agents for multiple
      myeloma (MM-I).
AB  - A series of degrasyn-like symmetrical compounds have been designed, synthesized,
      and screened against B cell malignancy (multiple myeloma, mantle cell lymphoma)
      cell lines. The lead compounds T5165804 and CP2005 showed higher nanomolar
      potency against these tumor cells in comparison to degrasyn and inhibited Usp9x
      activity in vitro and in intact cells. These observations suggest that this new
      class of compounds holds promise as cancer therapeutic agents. 

PMID- 24457093
TI  - Inhibition of IkappaB kinase-beta and IkappaB kinase-alpha by heterocyclic
      adamantyl arotinoids.
AB  - We recently reported on a series of retinoid-related molecules containing an
      adamantyl group, a.k.a. adamantyl arotinoids (AdArs), that showed significant
      cancer cell growth inhibitory activity and activated RXRalpha (NR2B1) in
      transient transfection assays while devoid of RAR transactivation capacity. We
      have now explored whether these AdArs could also bind and inhibit IKKbeta, a
      known target that mediates the induction of apoptosis and cancer cell growth
      inhibition by related AdArs containing a chalcone functional group. In addition,
      we have prepared and evaluated novel AdArs that incorporate a central
      heterocyclic ring connecting the adamantyl-phenol and the carboxylic acid at the
      polar termini. Our results indicate that the majority of the RXRalpha activating
      compounds lacked IKKbeta inhibitory activity. In contrast, the novel heterocyclic
      AdArs containing a thiazole or pyrazine ring linked to a benzoic acid motif were
      potent inhibitors of both IKKalpha and IKKbeta, which in most cases paralleled
      significant growth inhibitory and apoptosis inducing activities. 

PMID- 24457094
TI  - Synthesis of neolignans as microtubule stabilisers.
AB  - Tubulin is a well established target for anticancer drug development. Lignans and
      neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19
      exhibited significant anticancer activity against MCF-7 and MDAMB-231 human
      breast cancer cell lines. Both the compounds effectively induced stabilization of
      microtubule at 4 and 20 MUM concentrations respectively. Neolignan 10 induced
      G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19
      occupied the same binding pocket of paclitaxel with some difference in active
      site amino acids and good bioavailability of both the compounds. In in vivo acute
      oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.

PMID- 24457095
TI  - Rigid spiroethers targeting the decoding center of the bacterial ribosome.
AB  - Continuing our efforts towards understanding the principles governing ribosomal
      recognition and function, we have synthesized and evaluated a series of diversely
      functionalized 5,6-, 6,6- and 7,6-spiroethers. These compounds successfully mimic
      natural aminoglycosides regarding their binding to the decoding center of the
      bacterial ribosome. Their potential to inhibit prokaryotic protein production in
      vitro along with their antibacterial potencies have also been examined. 

PMID- 24457096
TI  - Characterization of the thalamic-subthalamic circuit involved in the placebo
      response through single-neuron recording in Parkinson patients.
AB  - The placebo effect, or response, is a complex phenomenon whereby an inert
      treatment can induce a therapeutic benefit if the subject is made to believe that
      it is effective. One of the main mechanisms involved is represented by
      expectations of clinical improvement which, in turn, have been found to either
      reduce anxiety or activate reward mechanisms. Therefore, the study of the placebo
      effect allows us to understand how emotions may affect both behavior and
      therapeutic outcome. The high rate of placebo responders in clinical trials of
      Parkinson's disease provided the motivation to investigate the biological
      underpinnings of the placebo response in Parkinsonian patients. The placebo
      effect in Parkinson's disease is induced through the administration of an inert
      substance which the patient believes to improve motor performance. By using this
      approach, different behavioral and neuroimaging studies have documented objective
      improvements in motor performance and an increase of endogenous dopamine release
      in both the dorsal and ventral striatum. Recently, single-neuron recording from
      the subthalamic and thalamic regions during the implantation of electrodes for
      deep brain stimulation has been used to investigate the firing pattern of
      different neurons before and after placebo administration. The results show that
      the subthalamic nucleus, the substantia nigra pars reticulata, and the ventral
      anterior thalamus are all involved in the placebo response in Parkinson patients,
      thus making intraoperative recording an excellent model to characterize the
      neuronal circuit that is involved in the placebo response in Parkinson's disease
      as well as in other disorders of movement. 

PMID- 24457097
TI  - Searching for the principles of brain plasticity and behavior.
AB  - An important development in behavioral neuroscience in the past 25 years has been
      the demonstration that the brain is far more flexible in structure and function
      than was previously believed. Studies of laboratory animals have provided an
      important tool for understanding the nature of brain plasticity and behavior at
      many levels ranging from detailed behavioral paradigms, electrophysiology,
      neuronal morphology, protein chemistry, and epigenetics. Here we seek a synthesis
      of the multidisciplinary work on brain plasticity and behavior to identify some
      general principles on how the brain changes in response to a wide range of
      experiences over the lifetime. 

PMID- 24457098
TI  - Sfrp1a and Sfrp5 function as positive regulators of Wnt and BMP signaling during
      early retinal development.
AB  - Axial patterning of the developing eye is critically important for proper axonal
      pathfinding as well as for key morphogenetic events, such as closure of the optic
      fissure. The dorsal retina is initially specified by the actions of Bone
      Morphogenetic Protein (BMP) signaling, with such identity subsequently maintained
      by the Wnt-beta catenin pathway. Using zebrafish as a model system, we
      demonstrate that Secreted frizzled-related protein 1a (Sfrp1a) and Sfrp5 work
      cooperatively to pattern the retina along the dorso-ventral axis. Sfrp1a/5
      depleted embryos display a reduction in dorsal marker gene expression that is
      consistent with defects in BMP- and Wnt-dependent dorsal retina identity. In
      accord with this finding, we observe a marked reduction in transgenic reporters
      of BMP and Wnt signaling within the dorsal retina of Sfrp1a/5 depleted embryos.
      In contrast to studies in which canonical Wnt signaling is blocked, we note an
      increase in BMP ligand expression in Sfrp1a/5 depleted embryos, a phenotype
      similar to that seen in embryos with inhibited BMP signaling. Overexpression of a
      low dose of sfrp5 mRNA causes an increase in dorsal retina marker gene
      expression. We propose a model in which Sfrp proteins function as facilitators of
      both BMP and Wnt signaling within the dorsal retina. 

PMID- 24457099
TI  - Otx2 expression in anterior neuroectoderm and forebrain/midbrain is directed by
      more than six enhancers.
AB  - Otx2 plays essential roles in each site at each step of head development. We
      previously identified the AN1 enhancer at 91kb 5' upstream for the Otx2
      expressions in anterior neuroectoderm (AN) at neural plate stage before E8.5, and
      the FM1 enhancer at 75kb 5' upstream and the FM2 enhancer at 122kb 3' downstream
      for the expression in forebrain/midbrain (FM) at brain vesicle stage after E8.5.
      The present study identified a second AN enhancer (AN2) at 88kb 5' upstream; the
      AN2 enhancer also recapitulates the endogenous Otx2 expression in choroid plexus,
      cortical hem and choroidal roof. However, the enhancer mutants indicated the
      presence of another AN enhancer. The study also identified a third FM enhancer
      (FM3) at 153kb 5' upstream. Thus, the Otx2 expressions in anterior neuroectoderm
      and forebrain/midbrain are regulated by more than six enhancers located far from
      the coding region. The enhancers identified are differentially conserved among
      vertebrates; none of the AN enhancers has activities in caudal forebrain and
      midbrain at brain vesicle stage after E8.5, nor do any of the FM enhancers in
      anterior neuroectoderm at neural plate stage before E8.5. 

PMID- 24457101
TI  - Autism spectrum disorders: picky eaters.

PMID- 24457100
TI  - Angiogenin interacts with the plasminogen activation system at the cell surface
      of breast cancer cells to regulate plasmin formation and cell migration.
AB  - Angiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to
      play a role in cell migration and tumor invasion, which involve proteolytic
      cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG
      regulates plasmin formation and cell migration was not known. Our studies here
      detected elevated levels of secreted and cell surface-bound ANG in highly
      invasive metastatic breast cancer cells. ANG was also detected at very high
      levels in the tumor cells in infiltrating ductal carcinomas. By
      immunofluorescence and immunoprecipitation analysis, ANG was detected at the
      leading edges of the cell surfaces where it colocalized and interacted with
      members of the plasminogen activation system (PAS) such as annexin A2 (A2),
      calpactin (S100-A10) and urokinase plasminogen activator receptor (uPAR).
      Analysis of lipid raft (LR) and non-lipid raft (NLR) regions of the cell
      membranes showed the predominance of ANG, A2 and S100-A10 in the LR regions. In
      contrast, uPAR was detected predominantly in the NLR fractions, suggesting that
      ANG interacts with uPAR at the junctions of LR and NLR regions. ANG knockdown in
      T47D and MDA-MB-231 breast cancer cell lines did not affect the cellular
      expression of A2, S100-A10 and uPAR but decreased cell migration and plasmin
      formation. Neutralization of ANG with monoclonal antibodies similarly decreased
      the migration of MDA-MB-231 cells. In the presence of ANG, uPAR was observed to
      interact with uPA, which is necessary for plasmin formation. Conversely, in the
      absence of ANG, uPAR did not interact with uPA and FAK and Src kinases were
      observed to be dephosphorylated. Exogenous addition of recombinant ANG to ANG
      knocked down MDA-MB-231 cells restored FAK phosphorylation, uPAR interactions
      with uPA, plasmin formation as well as migration of these cells. Taken together,
      our results identified a novel role for ANG as a member of the uPAR interactome
      that facilitates the interaction of uPAR with uPA, leading to plasmin formation
      and cell migration necessary for tumor invasion and metastasis of breast cancer
      cells. 

PMID- 24457103
TI  - Primary cilia disassembly down-regulates mechanosensitive hedgehog signalling: a
      feedback mechanism controlling ADAMTS-5 expression in chondrocytes.
AB  - OBJECTIVE: Hedgehog signalling is mediated by the primary cilium and promotes
      cartilage degeneration in osteoarthritis. Primary cilia are influenced by
      pathological stimuli and cilia length and prevalence are increased in
      osteoarthritic cartilage. This study aims to investigate the relationship between
      mechanical loading, hedgehog signalling and cilia disassembly in articular
      chondrocytes. METHODS: Primary bovine articular chondrocytes were subjected to
      cyclic tensile strain (CTS; 0.33 Hz, 10% or 20% strain). Hedgehog pathway
      activation (Ptch1, Gli1) and A Disintegrin And Metalloproteinase with
      Thrombospondin Motifs 5 (ADAMTS-5) expression were assessed by real-time PCR. A
      chondrocyte cell line generated from the Tg737(ORPK) mouse was used to
      investigate the role of the cilium in this response. Cilia length and prevalence
      were quantified by immunocytochemistry and confocal microscopy. RESULTS:
      Mechanical strain upregulates Indian hedgehog expression and activates hedgehog
      signalling. Ptch1, Gli1 and ADAMTS-5 expression were increased following 10% CTS,
      but not 20% CTS. Pathway activation requires a functioning primary cilium and is
      not observed in Tg737(ORPK) cells lacking cilia. Mechanical loading significantly
      reduced cilium length such that cilia became progressively shorter with
      increasing strain magnitude. Inhibition of histone deacetylase 6 (HDAC6), a
      tubulin deacetylase, prevented cilia disassembly and restored mechanosensitive
      hedgehog signalling and ADAMTS-5 expression at 20% CTS. CONCLUSIONS: This study
      demonstrates for the first time that mechanical loading activates primary cilia
      mediated hedgehog signalling and ADAMTS-5 expression in adult articular
      chondrocytes, but that this response is lost at high strains due to HDAC6
      mediated cilia disassembly. The study provides new mechanistic insight into the
      role of primary cilia and mechanical loading in articular cartilage.

PMID- 24457104
TI  - Modeling of signaling pathways in chondrocytes based on phosphoproteomic and
      cytokine release data.
AB  - OBJECTIVE: Chondrocyte signaling is widely identified as a key component in
      cartilage homeostasis. Dysregulations of the signaling processes in chondrocytes
      often result in degenerative diseases of the tissue. Traditionally, the
      literature has focused on the study of major players in chondrocyte signaling,
      but without considering the cross-talks between them. In this paper, we
      systematically interrogate the signal transduction pathways in chondrocytes, on
      both the phosphoproteomic and cytokine release levels. METHODS: The signaling
      pathways downstream 78 receptors of interest are interrogated. On the
      phosphoproteomic level, 17 key phosphoproteins are measured upon stimulation with
      single treatments of 78 ligands. On the cytokine release level, 55 cytokines are
      measured in the supernatant upon stimulation with the same treatments. Using an
      Integer Linear Programming (ILP) formulation, the proteomic data is combined with
      a priori knowledge of proteins' connectivity to construct a mechanistic model,
      predictive of signal transduction in chondrocytes. RESULTS: We were able to
      validate previous findings regarding major players of cartilage homeostasis and
      inflammation (e.g., IL1B, TNF, EGF, TGFA, INS, IGF1 and IL6). Moreover, we
      studied pro-inflammatory mediators (IL1B and TNF) together with pro-growth
      signals for investigating their role in chondrocytes hypertrophy and highlighted
      the role of underreported players such as Inhibin beta A (INHBA), Defensin beta 1
      (DEFB1), CXCL1 and Flagellin, and uncovered the way they cross-react in the
      phosphoproteomic level. CONCLUSIONS: The analysis presented herein, leveraged
      high throughput proteomic data via an ILP formulation to gain new insight into
      chondrocytes signaling and the pathophysiology of degenerative diseases in
      articular cartilage.

PMID- 24457105
TI  - Risk factors and survival outcome for non-elective referral in non-small cell
      lung cancer patients--analysis based on the National Lung Cancer Audit.
AB  - INTRODUCTION: Survival after diagnosis of lung cancer is poor and seemingly lower
      in the UK than other Western countries, due in large part to late presentation
      with advanced disease precluding curative treatment. Recent research suggests
      that around one-third of lung cancer patients reach specialist care after
      emergency presentation and have a worse survival outcome. Confirmation of these
      data and understanding which patients are affected may allow a targeted approach
      to improving outcomes. METHODS: We used data from the UK National Lung Cancer
      Audit in a multivariate logistic regression model to quantify the association of
      non-elective referral in non-small cell lung cancer patients with covariates
      including age, sex, stage, performance status, co-morbidity and socioeconomic
      status and used the Kaplan-Meier method and Cox proportional hazards model to
      quantify survival by source of referral. RESULTS: In an analysis of 133,530 cases
      of NSCLC who presented 2006-2011, 19% of patients were referred non-electively
      (following an emergency admission to hospital or following an emergency
      presentation to A&E). This route of referral was strongly associated with more
      advanced disease stage (e.g. in Stage IV - OR: 2.34, 95% CI: 2.14-2.57, p<0.001)
      and worse performance status (e.g. in PS 4 - OR: 7.28, 95% CI: 6.75-7.86,
      p<0.001), but was also independently associated with worse socioeconomic status,
      and extremes of age. These patients were more likely to have died within 1 year
      of diagnosis (hazard ratio of 1.51 (95% CI: 1.49-1.54) after adjustment for key
      clinical variables. CONCLUSION: Our data confirm and quantify poorer survival in
      lung cancer patients who are referred non-electively to specialist care, which is
      more common in patients with poorer performance status, higher disease stage and
      less advantaged socioeconomic status. Work to tackle this late presentation
      should be urgently accelerated, since its realisation holds the promise of
      improved outcomes and better healthcare resource utilisation.

PMID- 24457106
TI  - [Interruption of the aortic arch with no patent ductus arteriosus: is survival
      possible?].
AB  - Interruption of the aortic arch is a rare congenital disease. It is defined by
      the complete interruption between the ascending and descending aorta. A patent
      ductus arteriosus is necessary to maintain flow from the pulmonary to the
      descending aorta. Its closure leads to a cardiovascular collapse and this
      malformation is therefore duct-dependent. However, in rare cases, survival
      remains possible even after ductus arteriosus closure. We report such a case. 

PMID- 24457107
TI  - [Necrotizing enterocolitis: what role is played by cytomegalovirus?].

PMID- 24457108
TI  - [Neonatal renal candidiasis: a case report].
AB  - Neonatal renal candidiasis is an increasingly common condition affecting
      predominantly premature infants receiving neonatal intensive care or term infants
      with urogenital tract anomalies. CASE REPORT: a female infant was born by
      cesarian section at 30 weeks' gestation to a mother whose pregnancy had been
      complicated by rupture of membranes for 5 days. The infant was admitted at birth,
      maternofetal bacterial infection was suspected, and intravenous antibiotics were
      prescribed. The patient developed sepsis caused by Klebsiella pneumoniae at the
      age of 13 days. She was referred to our hospital at the age of 50 days because of
      renal abscess. At admission, the baby presented with hypothermia and abdominal
      distention. Renal ultrasonography findings were compatible with fungal disease.
      Blood, urine, and cerebrospinal fluid cultures were negative for fungi; however,
      galactomannan antigen blood levels were increased. Amphotericin B was
      administered for 6 weeks. End-organ evaluation of the heart, brain, and eyes did
      not demonstrate disseminated infection. The patient was discharged with a
      prescription for oral fluconazole and remained well at follow-up.

PMID- 24457109
TI  - [Video games: are the motivations and intensity of use changing with age?
      Comparison between a population of adolescent and adult gamers].
AB  - Despite the popularity of video games, few studies have been conducted in France
      on their use. The objective of this study was to gather data from a sample of
      French video game players to learn more about this population. This approach also
      aimed to examine whether differences exist between adolescent and adult gamers in
      terms of their motivations to play and whether this practice met the criteria for
      problem video game playing. A questionnaire collecting sociodemographic data and
      assessing the problems associated with the use of video games, as well as
      motivations to play, was distributed during a video game festival and on the
      Internet. A total of 778 people responded to the questionnaire. The results
      showed that there were few differences between adolescent and adult gamers. Both
      groups had an intense video game habit. The majority of them sometimes had the
      feeling of losing control of their use and sacrificed other activities to play
      video games. This last dimension was most frequently cited by adults. The feeling
      of spending more time playing was most frequently cited by adolescents.
      Concerning motivations to play, the two groups differed only on the score of the
      "social" dimension, significantly higher among adolescents.

PMID- 24457110
TI  - [Pasteurella multocida meningitis with cerebral abscesses].
AB  - Pasteurella multocida is classically responsible for local soft tissue infections
      secondary to dog bites or cat scratches. It can be responsible for meningitis in
      infants and elderly persons. We report the case history of a 5-year-old male
      child admitted to our pediatric unit for meningitis. Cerebrospinal fluid analysis
      revealed an infection with P. multocida. The suspected mode of contamination was
      either from the saliva of a pet dog or through an unnoticed skull fracture
      sustained after an accident 1 year prior to the occurrence of meningitis. In
      spite of the neurologic complication (cerebral abscess), the progression was
      favorable after drainage of the abscess, 5 weeks of parenteral treatment, and 3
      weeks of oral antibiotic therapy. Meningitis due to Pasteurella sp. is rare and
      can lead to neurologic complications. The notion of bites or scratches can be
      absent and the mode of contamination is sometimes difficult to unveil.

PMID- 24457111
TI  - [Can you do away with anti-nausea drugs in pediatrics?].

PMID- 24457112
TI  - Mechanical response of brain tissue under blast loading.
AB  - In this study, a framework for understanding the propagation of stress waves in
      brain tissue under blast loading has been developed. It was shown that tissue
      nonlinearity and rate dependence are the key parameters in predicting the
      mechanical behavior under such loadings, as they determine whether traveling
      waves could become steeper and eventually evolve into shock discontinuities. To
      investigate this phenomenon, in the present study, brain tissue has been
      characterized as a quasi-linear viscoelastic (QLV) material and a nonlinear
      constitutive model has been developed for the tissue that spans from medium
      loading rates up to blast rates. It was shown that development of shock waves is
      possible inside the head in response to high rate compressive pressure waves.
      Finally, it was argued that injury to the nervous tissue at the microstructural
      level could be partly attributed to the high stress gradients with high rates
      generated at the shock front and this was proposed as a mechanism of injury in
      brain tissue. 

PMID- 24457113
TI  - Plasma somatostatin-like immunoreactivity increases in the plasma of septic
      patients and rats with systemic inflammatory reaction: experimental evidence for
      its sensory origin and protective role.
AB  - Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11
      systemic inflammatory response syndrome (SIRS) patients were investigated in
      correlation with cytokines, adhesion molecules and coagulation markers repeatedly
      during 4 days. The origin and role of SST were studied in the cecum ligation and
      puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves
      were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a
      separate group animals were treated with the somatostatin receptor antagonist
      cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic
      patients compared to healthy volunteers during the whole 4-day period.
      Significantly decreased Horowitz score showed severe lung injury, increased
      plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin,
      tissue plasminogen activator and the interleukin 8 and monocyte chemotactic
      protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not
      change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly
      increased in rats both in the plasma and the lung 6h after CLP compared to sham
      operation. After RTX pretreatment SST-LI was not altered in intact animals, but
      the SIRS-induced elevation was absent. Lung MPO activity significantly increased
      6h following CLP compared to sham operation, which was significantly higher both
      after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats
      survived the 6h, but 60% of the RTX-pretreated ones died showing a significantly
      worse survival. This is the first comprehensive study in humans and animal
      experiments providing evidence that SST is released from the activated
      peptidergic sensory nerves. It gets into the bloodstream and mediates a potent
      endogenous protective mechanism. 

PMID- 24457114
TI  - Blood levels of adrenomedullin on admission predict outcomes after acute
      intracerebral hemorrhage.
AB  - Increased plasma adrenomedullin level has been associated with critical illness.
      This study aimed to investigate the correlations of plasma adrenomedullin
      concentration with 3-month clinical outcomes and early neurological deterioration
      of patients with acute intracerebral hemorrhage. One hundred fourteen patients
      and 112 healthy controls were recruited. Relationships of plasma adrenomedullin
      concentrations with early neurological deterioration, 3-month mortality and
      unfavorable outcome (modified Rankin Scale score >2) were evaluated. Plasma
      adrenomedullin concentrations were increased in patients than in healthy
      individuals and were highly associated with National Institutes of Health Stroke
      Scale scores. A multivariate analysis selected plasma adrenomedullin
      concentration as an independent predictor for 3-month clinical outcomes and early
      neurological deterioration. A receiver operating characteristic curve analysis
      showed plasma adrenomedullin concentration predicted 3-month clinical outcomes
      and early neurological deterioration with high area under curves. The predictive
      value of adrenomedullin was similar to that of National Institutes of Health
      Stroke Scale score. In a combined logistic-regression model, adrenomedullin did
      not improve the predictive value of National Institutes of Health Stroke Scale
      score. Thus, elevated plasma adrenomedullin concentration is highly associated
      with 3-month clinical outcomes and early neurological deterioration of patients
      with acute intracerebral hemorrhage. 

PMID- 24457115
TI  - Transient increment of HTLV-2 proviral load in HIV-1-co-infected patients during
      treatment intensification with raltegravir.
AB  - BACKGROUND: Numerous studies have analyzed the effects of raltegravir
      intensification on HIV-1 viral replication in infected individuals receiving
      suppressive combined antiretroviral treatment (cART). Nevertheless, there are
      only two studies on the effect of raltegravir in HTLV-1 infection, and none in
      HTLV-2. OBJECTIVE: To study the effect of raltegravir on HTLV-2 infection in HIV
      1-co-infected individuals. STUDY DESIGN: This retrospective longitudinal study
      included four HTLV-2-HIV-1-co-infected individuals who received raltegravir-based
      cART during 48 weeks and 11 HTLV-2-HIV-1-co-infected individuals under cART
      without raltegravir during 48 weeks. HTLV-2 proviral load, CD4 and CD8 count and
      frequency were analyzed. RESULTS: HTLV-2 proviral load significantly increased at
      week 24 compared to baseline among all the patients who received raltegravir
      (p=0.003), while no significant increases were found in the control group. No
      significant variation in either CD8 or CD4 counts was found during the follow up
      in both groups. CONCLUSIONS: Raltegravir induced a transient increment on total
      HTLV-2 DNA proviral load in HTLV-2/HIV-1-coinfected individuals on suppressive
      cART after 24 weeks.

PMID- 24457116
TI  - Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a
      cluster of adult patients.
AB  - BACKGROUND: Hand foot and mouth disease (HFMD) is a common childhood
      manifestation of enterovirus (EV) infection. It predominantly affects young
      children, and has been mainly associated with coxsackievirus (CV) A16 and EV 71.
      OBJECTIVES: We report an unusual cluster of adult patients with HFMD. STUDY
      DESIGN: Throat swabs and vesicular fluid samples obtained from patients admitted
      to the emergency room (ER) with HFMD were tested for EV by reverse transcription
      (RT)-real time PCR, and further subjected to sequencing and phylogenetic
      analysis. RESULTS: CVA6 was identified as the causative agent of HFMD in five
      epidemiologically-unrelated adult patients (28-37 years old) admitted to the ER
      between December 2012 and February 2013. Phylogenetic analysis mapped the CVA6
      strains into one cluster. All patients manifested with fever and a severe
      vasculitis-like rash, followed by spontaneous recovery. CONCLUSIONS: This cluster
      identifies CVA6 as an emerging cause of HFMD of unusual age distribution,
      seasonality, and clinical severity, underscoring the need for continued alertness
      and clinical-genotypic surveillance of EV HFMD.

PMID- 24457117
TI  - Special considerations for prophylaxis for and treatment of anthrax in pregnant
      and postpartum women.
AB  - In August 2012, the Centers for Disease Control and Prevention, in partnership
      with the Association of Maternal and Child Health Programs, convened a meeting of
      national subject matter experts to review key clinical elements of anthrax
      prevention and treatment for pregnant, postpartum, and lactating (P/PP/L) women.
      National experts in infectious disease, obstetrics, maternal fetal medicine,
      neonatology, pediatrics, and pharmacy attended the meeting, as did
      representatives from professional organizations and national, federal, state, and
      local agencies. The meeting addressed general principles of prevention and
      treatment for P/PP/L women, vaccines, antimicrobial prophylaxis and treatment,
      clinical considerations and critical care issues, antitoxin, delivery concerns,
      infection control measures, and communication. The purpose of this meeting
      summary is to provide updated clinical information to health care providers and
      public health professionals caring for P/PP/L women in the setting of a
      bioterrorist event involving anthrax. 

PMID- 24457119
TI  - The genetic basis and expanding role of molecular analysis in the diagnosis,
      prognosis, and therapeutic design for myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders
      of ineffective hematopoiesis that characteristically demonstrate peripheral blood
      cytopenia, bone marrow hypercellularity, and morphologically defined dysplasia of
      one or more hematopoietic lineages. Classical metaphase cytogenetics and
      judicious use of fluorescence in situ hybridization play central roles in the
      contemporary diagnosis and classification of MDS. An abundance of recent
      molecular studies are beginning to delineate additional genetic and epigenetic
      aberrations associated with these disorders. These alterations affect diagnosis,
      prognosis, and therapy, and with this understanding classification systems are
      evolving from a primarily hematological and morphological basis toward a
      multifactorial appreciation that includes histomorphology, metaphase
      cytogenetics, and directed molecular studies. In the present health-care
      environment, it is critical to develop a cost-effective, efficient testing
      strategy that maximizes the diagnostic potential of even limited specimens. Here,
      we briefly review the classical genetic approach to MDS, outline exciting new
      advances in the molecular understanding of this heterogeneous group of
      hematological neoplasms, and discuss how these advances are driving the evolution
      of classification and prognostic systems. Rapidly growing understanding of the
      genetic basis of MDS holds much promise for testing, and here we provide a frame
      of reference for discussion of current testing protocols and for addressing
      testing modalities likely to enter clinical practice in the near future. 

PMID- 24457118
TI  - Toxoplasma gondii-skeletal muscle cells interaction increases lipid droplet
      biogenesis and positively modulates the production of IL-12, IFN-g and PGE2.
AB  - BACKGROUND: The interest in the mechanisms involved in Toxoplasma gondii lipid
      acquisition has steadily increased during the past few decades, but it remains
      not completely understood. Here, we investigated the biogenesis and the fate of
      lipid droplets (LD) of skeletal muscle cells (SkMC) during their interaction with
      T. gondii by confocal and electron microscopy. We also evaluated whether infected
      SkMC modulates the production of prostaglandin E2 (PGE2), cytokines interleukin
      12 (IL-12) and interferon-gamma (INF-g), and also the cyclooxygenase-2 (COX-2)
      gene induction. METHODS: Primary culture of skeletal muscle cells were infected
      with tachyzoites of T. gondii and analysed by confocal microscopy for observation
      of LD. Ultrastructural cytochemistry was also used for lipid and sarcoplasmatic
      reticulum (SR) detection. Dosage of cytokines (IL-12 and INF-g) by ELISA
      technique and enzyme-linked immunoassay (EIA) for PGE2 measurement were employed.
      The COX-2 gene expression analysis was performed by real time reverse
      transcriptase polymerase chain reaction (qRT-PCR). RESULTS: We demonstrated that
      T. gondii infection of SkMC leads to increase in LD number and area in a time
      course dependent manner. Moreover, the ultrastructural analysis demonstrated that
      SR and LD are in direct contact with parasitophorous vacuole membrane (PVM),
      within the vacuolar matrix, around it and interacting directly with the membrane
      of parasite, indicating that LD are recruited and deliver their content inside
      the parasitophorous vacuole (PV) in T. gondii-infected SkMC. We also observed a
      positive modulation of the production of IL-12 and IFN-g, increase of COX-2 mRNA
      levels in the first hour of T. gondii-SkMC interaction and an increase of
      prostaglandin E2 (PGE2) synthesis from 6 h up to 48 h of infection. CONCLUSIONS:
      Taken together, the close association between SR and LD with PV could represent a
      source of lipids as well as other nutrients for the parasite survival, and
      together with the increased levels of IL-12, INF-g and inflammatory indicators
      PGE2 and COX-2 might contribute to the establishment and maintenance of chronic
      phase of the T. gondii infection in muscle cell.

PMID- 24457120
TI  - Getting things backwards to prevent primer dimers.
AB  - This Commentary highlights the article by Satterfield that describes a new class
      of primer technology-cooperative primers, which prevent primer-dimer
      amplification. 

PMID- 24457121
TI  - Sorafenib-based combination as a first line treatment for advanced hepatocellular
      carcinoma: a systematic review of the literature.
AB  - BACKGROUND: Hepatocellular carcinoma is the fifth most common cancer worldwide
      and the third most common cause of cancer mortality. Advanced HCC is a distinct
      disease entity with limited approved treatment options and grave prognosis. So,
      we will explore in this systematic review the value of using sorafenib-based
      combination in this poor prognosis subset of HCC. METHODS: PubMed, Medline, the
      Cochrane Library, trip database and Google Scholar were searched using the terms
      "Hepatocellular carcinoma" OR "Hepatoma" or "Liver cancer" AND "systemic
      anticancer therapy" AND "Sorafenib" and specifying only English literature.
      Outcomes of interest included progression free survival and overall survival (PFS
      and OS), tumor response, and toxicities. RESULTS: A total of 17 potentially
      relevant trials was identified, of which 9 studies were excluded. Hence, eight
      trials involving 272 patients were included. Median PFS was reported in 6 out of
      the 8 trials ranging from 3.7 to 7.5 months. Median OS was reported in 6 out of
      the 8 studies ranging from 7.4 to 40.1 months. The DCR was reported in the 8
      studies, ranging from 48.7% to 76%. Frequently reported Grade 3/4 toxicities were
      increased AST/ALT, fatigue, hypertension, hand foot skin reaction and diarrhea.
      However, some chemotherapy-specific side effects were noted in some studies.
      CONCLUSIONS: The current evidence from the available clinical trials suggests
      that sorafenib-based combination with some anticancer agents (especially mTOR
      inhibitors) could be a more effective and tolerable treatment for advanced HCC in
      the future. However, such sorafenib-based combination cannot be recommended
      outside the setting of clinical trials.

PMID- 24457122
TI  - The peripheral antinociceptive effect induced by the heme oxygenase/carbon
      monoxide pathway is associated with ATP-sensitive K+ channels.
AB  - Carbon monoxide (CO), a product of the enzyme heme oxygenase (HO), has been
      recognized to act as an atypical neurotransmitter or neuromodulator in the
      nervous system, and several lines of evidence suggest that CO may play a role
      through multiple mechanisms in nociceptive processing. Therefore, the aim of our
      study was to assess the interaction between the HO/CO pathway and ATP-sensitive
      K+ channels in hypernociception in response to carrageenan. The electronic von
      Frey and Randall Selitto tests were applied before and after intraplantar
      carrageenan administration. The intraplantar hemin carrageenan administration (HO
      substrate) into the right hindpaw elicited an antinociceptive effect, which was
      determined to be local because it produced no effect when injected into the
      contralateral paw. The administration of a HO pathway inhibitor was capable of
      potentiating the hypersensitivity evoked by carrageenan. Among the three
      different HO products, CO appears to be the one that attenuated the nociceptive
      response, whereas biliverdin and iron (II) sulfate failed to cause any
      significant changes. This blockade of the carrageenan mechanical hyperalgesia
      induced by the hemin was antagonized by the administration of glybenclamide, and
      a combination of hemin and diazoxide decreased the hyperalgesic action of
      carrageenan. These results also suggest that an endogenous opioid system may not
      be involved because naloxone did not affect the hemin-induced antinociception in
      the carrageenan model. Our study provides evidence that the peripheral
      antinociceptive effect of the HO/CO pathway may result from the activation of ATP
      sensitive K+ channels.

PMID- 24457123
TI  - Chlorogenic acid attenuates lipopolysaccharide-induced mice mastitis by
      suppressing TLR4-mediated NF-kappaB signaling pathway.
AB  - Chlorogenic acid (CGA), one of the most abundant polyphenols in the diet, has
      been reported to have potent anti-inflammatory properties. However, the effect of
      CGA on lipopolysaccharide (LPS)-induced mice mastitis has not been investigated.
      The purpose of the present study was to elucidate whether CGA could ameliorate
      the inflammation response in LPS-induced mice mastitis and to clarify the
      possible mechanism. The mouse model of mastitis was induced by injection of LPS
      through the duct of mammary gland. CGA was administered intraperitoneally with
      the dose of 12.5, 25, and 50mg/kg respectively 1h before and 12h after induction
      of LPS. In this study, the effect of CGA on LPS-induced mice mastitis was
      assessed through histopathological examination, ELISA assay, and western blot
      analysis. The results showed that CGA significantly reduced TNF-alpha, IL-1beta,
      and IL-6 production compared with LPS group. Besides, western blot analysis
      showed that CGA could inhibit the expression of TLR4 and the phosphorylation of
      NF-kappaB and IkappaB induced by LPS. These results suggested that anti
      inflammatory effects of CGA against LPS-induced mastitis may be due to its
      ability to inhibit TLR4-mediated NF-kappaB signaling pathway. Therefore, CGA may
      be a potent therapeutic reagent for the prevention of the immunopathology
      encountered during Escherichia coli elicited mastitis. 

PMID- 24457124
TI  - Kv7 channels as targets for anti-epileptic and psychiatric drug-development.
AB  - The Kv7 channels, a family of voltage-dependent K(+) channels (Kv7.1-Kv7.5), have
      gained much attention in drug discovery especially because four members are
      genetically linked to diseases. For disorders of the CNS focus was originally on
      epilepsy and pain, but it is becoming increasingly evident that Kv7 channels can
      also be valid targets for psychiatric disorders, such as anxiety and mania. The
      common denominator is probably neuronal hyperexcitability in different brain
      areas, which can be successfully attenuated by pharmacological increment of Kv7
      channel activity. This perspective attempts to review the current status and
      challenges for CNS drug discovery based on Kv7 channels as targets for
      neurological and psychiatric indications with special focus on selectivity and
      mode-of-actions. 

PMID- 24457125
TI  - Reversibility of effectively treated chemotherapy-related heart failure: raising
      our awareness and a call to action for cardiology.

PMID- 24457126
TI  - Faecal transplantation for Clostridium difficile infection. Three cases treated
      in Italy.

PMID- 24457127
TI  - Pilomatricoma of the cheek: a benign tumor mimicking metastatic squamous cell
      carcinoma on FDG PET/CT.
AB  - BACKGROUND: Pilomatricomas are benign skin tumors originating from hair matrix
      cells in the dermal layer of the skin, especially in the head and neck region.
      They may mimick malignant lesions on fine-needle aspirate cytology. METHODS: This
      is a case report of a pilomatricoma of the cheek which was initially diagnosed as
      squamous cell carcinoma on fine-needle aspirate cytology. As part of the staging
      work-up, a PET/CT scan was performed, revealing a FDG-avid superficial cheek
      lesion and also an ipsilateral FDG-avid level II cervical lymph node, giving the
      impression of metastatic squamous cell carcinoma. RESULTS: The cheek lesion, as
      well as the cervical lymph node was excised. The final histology showed benign
      pilomatricoma and reactive lymphadenopathy. CONCLUSION: Pilomatricoma should be
      considered as an uncommon differential diagnosis for an FDG-avid cutaneous lesion
      on PET/CT, even in the presence of ipsilateral FDG-avid cervical lymphadenopathy.

PMID- 24457128
TI  - Arteriovenous fistula presenting as a failed hearing test.
AB  - Congenital arteriovenous fistulas (AVFs) result from inadequate differentiation
      of the vascular system during fetal development. This case report describes an
      AVF of the neck, which possibly manifested as noise interference during a newborn
      hearing-screening test by otoacoustic emissions (OAEs). This report is in
      compliance with the institutional review board regulations of the University of
      Puerto Rico School of Medicine. 

PMID- 24457129
TI  - Adenocarcinoma of the anterior tongue.

PMID- 24457130
TI  - Evidence for two different morphotypes of Difflugia tuberspinifera from China.
AB  - Difflugia is a morphologically diverse genus of testate amoebae, which are common
      components of freshwater ecosystems. We observed a new morphotype similar to
      Difflugia tuberspinifera but without spine in four Xiamen reservoirs, Fujian
      Province, southeast China. We investigated its morphology and biometry using
      light and scanning electron microscopy. The linear discriminant analysis and
      principal component analysis of biometric characters revealed that the spiny and
      spineless forms of D. tuberspinifera differed only in the presence or absence of
      spine. Shell height, shell diameter, aperture diameter and collar height did not
      differ significantly between the two morphotypes. The number of conical spines
      varies from 0 to 8. However, the distribution of spine numbers showed two main
      modes at 0 (spineless form 45.1% of individuals) and 4-6 (38.9%), suggesting the
      possible existence of two genetically distinct lineages. Spines may have
      ecological and evolutionary significance. Our results suggested that the spiny
      and spineless morphotypes of D. tuberspinifera represent either a single variable
      taxon with different ecotypes or sibling species. Further morphological studies
      on clonal variations and molecular approaches are needed to clarify if the
      spineless morph represents an independent species or not. 

PMID- 24457131
TI  - Morphology and phylogeny of Henneguya jocu n. sp. (Myxosporea, Myxobolidae),
      infecting the gills of the marine fish Lutjanus jocu.
AB  - Henneguya jocu n. sp. (Myxosporea, Myxobolidae) is described from the gill
      lamellae of the marine teleost fish Lutjanus jocu, with a focus on
      ultrastructural and molecular features. This myxosporean forms subspherical cysts
      up to ~260 MUm * 130 MUm long, and develops asynchronously. Mature myxospores
      ellipsoidal with a bifurcated caudal process. Myxospore length 10.9 +/- 0.4 MUm
      (n=50); width, 8.2 +/- 0.3 MUm (n=50); and thickness, 2.9 +/- 0.5 MUm (n=50). Two
      equal caudal processes, 34.1+/-1.0 MUm long (n=50); and total myxospore length,
      45.2 +/- 1.0 MUm (n=50). Two symmetric valves surround two ellipsoidal polar
      capsules, 5.0 +/- 0.3 * 1.4 +/- 0.2 MUm (n=20), each containing an isofilar polar
      filament forming 4-5 coils along the inner wall of these structures, as well as a
      binucleated sporoplasm presenting a spherical vacuole and several globular
      sporoplasmosomes. Both the morphological data and molecular analysis of the SSU
      rDNA gene identify this parasite as a new species of the genus Henneguya. Maximum
      Likelihood and Maximum Parsimony analyses further indicate that the parasite
      clusters within others marine Myxobolidae species, forming a group alongside
      other Henneguya species described from marine hosts.

PMID- 24457132
TI  - Concentration and distribution of PCNs in ambient soil of a municipal solid waste
      incinerator.
AB  - The impact of a typical municipal solid waste incinerator (MSWI) on
      polychlorinated naphthalene (PCN) concentrations in surrounding soil was studied.
      We collected 6 stack gas samples from the MSWI and 21 soil samples from sampling
      sites at distances of between 300 and 1,700 m from the MSWI stack. Total dl-PCN
      (dioxin-like PCN) concentrations in the stack gas samples ranged from 6898 and
      89,032 pg m(-3), with a mean value of 36,241 pg m(-3). The total dl-PCN
      concentrations in the soil samples ranged from 30.35 to 280.9 pg g(-1), with a
      mean value of 87.03 and a median value of 70.32 pg g(-1), while the TEQ values
      were between 7.7 and 130.2 fg TEQ g(-1), with a mean value of 41.12 fg TEQ g(-1)
      and a median value of 31.52fg TEQ g(-1). The PCN homologue patterns and the
      results of Principal Component Analysis suggested that the MSWI may be a source
      of PCNs in the soils. A contour map, created using an ordinary Kriging
      interpolation technique, showed that a limited area (<= 1,000 m radius)
      surrounding the MSWI was influenced by the emissions from the MSWI. Furthermore,
      an exponential function equation was proposed to quantify the relationship
      between TEQs of PCNs and the distance from the stack.

PMID- 24457133
TI  - Water-supply options in arsenic-affected regions in Cambodia: targeting the
      bottom income quintiles.
AB  - In arsenic-affected regions of Cambodia, rural water committees and planners can
      choose to promote various arsenic-avoidance and/or arsenic-removal water supply
      systems. Each of these has different costs of providing water, subsequently born
      by the consumer in order to be sustainable. On a volumetric basis ($/m3-yr) and
      of the arsenic-avoidance options considered, small-scale public water supply -
      e.g., treated water provided to a central tap stand - is the most expensive
      option on a life-cycle cost basis. Rainwater harvesting, protected hand dug
      wells, and vendor-supplied water are the cheapest with a normalized present worth
      value, ranging from $2 to $10 per cubic meter per year of water delivered.
      Subsidization of capital costs is needed to make even these options affordable to
      the lowest (Q5) quintile. The range of arsenic-removal systems considered here,
      using adsorptive media, is competitive with large-scale public water supply and
      deep tube well systems. Both community level and household-scale systems are in a
      range that is affordable to the Q4 quintile, though more research and field
      trials are needed. At a target cost of $5.00/m3, arsenic removal systems will
      compete with the OpEx costs for most of the arsenic-safe water systems that are
      currently available. The life-cycle cost approach is a valuable method for
      comparing alternatives and for assessing current water supply practices as these
      relate to equity and the ability to pay.

PMID- 24457134
TI  - A framework to facilitate consistent characterization of read across uncertainty.
AB  - A process for evaluating analogues for use in structure activity relationship
      (SAR) assessments was previously published (Wu et al., 2010) and tested using a
      series of case studies (Blackburn et al., 2011). SAR-based "read across"
      approaches continue to be broadly used to address toxicological data gaps. The
      potential additional uncertainty introduced into risk assessments as a result of
      application of read across approaches to fill data gaps has been widely discussed
      (OECD, 2007; ECETOC, 2012; Patlewicz et al., 2013), but to date a systematic
      framework to guide the characterization of uncertainty in read across assessments
      has not been proposed. The current manuscript presents both a systematic
      framework to describe potential areas of additional uncertainty that may arise in
      read across (evaluated based on the number and suitability of analogues
      contributing data, severity of the critical effect, and effects and potency
      concordance), as well as a questionnaire for evaluating and documenting
      consideration of these potential additional sources of uncertainty by risk
      assessors. Application of this framework represents a next step in standardizing
      the read across process, both by providing a means to transparently assign a
      level of uncertainty to a SAR-based read across assessment and by facilitating
      consistency in read across conclusions drawn by different risk assessors. 

PMID- 24457135
TI  - The effects of functional electrical stimulation on upper-extremity function and
      cortical plasticity in chronic stroke patients.

PMID- 24457136
TI  - Serial and prolonged EEG monitoring in anti-N-Methyl-d-Aspartate receptor
      encephalitis.
AB  - OBJECTIVE: To describe serial electroencephalographic (EEG) findings of three
      patients with anti-NMDAR encephalitis. METHODS: Three women (age 15-34years) with
      confirmed anti-NMDAR encephalitis underwent serial EEG recordings. Continuous EEG
      for 72h was performed in one case and 3-day video-EEG monitoring was obtained in
      two cases. RESULTS: Generalized rhythmic delta activity (GRDA) was found in all
      patients. GRDA persisted for hours, but was not continuous on a 24-h EEG
      recording, disclosed no frequency, voltage or field evolution, and was not seen
      on the first EEG of two patients. Extreme delta brush was noted in two patients
      who presented more severe disease. One patient presented seizures, which were
      electrographically and clinically different from the GRDA pattern and from
      dyskinetic movements. CONCLUSIONS: Serial or continuous EEG may be necessary to
      detect GRDA in anti-NMDAR patients. To avoid unnecessary treatment, this pattern
      should not be interpreted as indicative of ictal activity, unless there is
      evidence of its ictal nature. SIGNIFICANCE: Our findings may contribute to the
      diagnosis of anti-NMDAR encephalitis in cases with characteristic clinical
      picture.

PMID- 24457137
TI  - Decreased movement-related beta desynchronization and impaired post-movement beta
      rebound in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: This study explored event-related desynchronization (ERD) and
      synchronization (ERS) in amyotrophic lateral sclerosis (ALS) to quantify cortical
      sensorimotor processes during volitional movements. We furthermore compared
      ERD/ERS measures with clinical scores and movement-related cortical potential
      (MRCP) amplitudes. METHODS: Electroencephalograms were recorded while 21 ALS
      patients and 19 controls performed two self-paced motor tasks: sniffing and right
      index finger flexion. Based on Wavelet analysis the alpha and beta frequency
      bands were selected for subsequent evaluation. RESULTS: Patients generated
      significantly smaller resting alpha spectral power density (SPD) and smaller beta
      ERD compared to controls. Additionally patients exhibited merely unilateral post
      movement ERS (beta rebound) whereas this phenomenon was bilateral in controls.
      ERD/ERS amplitudes did not correlate with corresponding MRCPs for either patients
      or controls. CONCLUSIONS: The smaller resting alpha SPD and beta ERD and
      asymmetrical appearance of beta ERS in patients compared to controls could be the
      result of pyramidal cell degeneration and/or corpus callosum involvement in ALS.
      SIGNIFICANCE: These results support the notion of reduced movement preparation in
      ALS involving also areas outside the motor cortex. Furthermore post-movement
      cortical inhibition seems to be impaired in ALS. ERD/ERS and MRCP are found to be
      independent measures of cortical motor functions in ALS.

PMID- 24457138
TI  - Avian influenza A(H7N9) virus infection in pregnant woman, China, 2013.

PMID- 24457139
TI  - Analysis of diffusion tensor imaging metrics for gliomas grading at 3 T.
AB  - OBJECTIVES: To assess the diagnostic accuracy of axial diffusivity (AD), radial
      diffusivity (RD), apparent diffusion coefficient (ADC) and fractional anisotropy
      (FA) values derived from DTI for grading of glial tumors, and to estimate the
      correlation between DTI parameters and tumor grades. METHODS: Seventy-eight
      patients with glial tumors underwent DTI. AD, RD, ADC and FA values of tumor,
      peritumoral edema and contralateral normal-appearing white matter (NAWM) and AD,
      RD, ADC and FA ratios: lowest average AD, RD, ADC and FA values in tumor or
      peritumoral edema to AD, RD, ADC and FA of NAWM were calculated. DTI parameters
      and tumor grades were analyzed statistically and with Pearson correlation.
      Receiver operating characteristic (ROC) curve analysis was also performed.
      RESULTS: The differences in ADC, AD and RD tumor values, and ADC and RD tumor
      ratios were statistically significant between grades II and III, grades II and
      IV, and between grades II and III-IV. The AD tumor ratio differed significantly
      among all tumor grades. Tumor ADC, AD, RD and glial tumor grades were strongly
      correlated. In the ROC curve analysis, the area under the curve (AUC) of the
      parameter tumor ADC was the largest for distinguishing grade II from grades III
      to IV (98.5%), grade II from grade IV (98.9%) and grade II from grade III
      (97.0%). CONCLUSION: ADC, RD and AD are useful DTI parameters for differentiation
      between low- and high-grade gliomas with a diagnostic accuracy of more than 90%.
      Our study revealed a good inverse correlation between ADC, RD, AD and WHO grades
      II-IV astrocytic tumors.

PMID- 24457140
TI  - Alveolar echinococcosis of the liver: diffusion-weighted MRI findings and
      potential role in lesion characterisation.
AB  - PURPOSE: To report the diffusion-weighted MRI findings in alveolar echinococcosis
      (AE) of the liver and evaluate the potential role of apparent diffusion
      coefficients (ADCs) in the characterisation of lesions. MATERIALS AND METHODS: We
      retrospectively included 22 patients with 63 AE liver lesions (>=1 cm), examined
      with 3-T liver MRI, including a free-breathing diffusion-weighted single-shot
      echo-planar imaging sequence (b-values=50, 300 and 600 s/mm(2)). Two radiologists
      jointly assessed the following lesion features: size, location, presence of
      cystic and/or solid components (according to Kodama's classification system),
      relative contrast enhancement, and calcifications (on CT). The ADC(total),
      ADC(min) and ADC(max) were measured in each lesion and the surrounding liver
      parenchyma. RESULTS: Three type 1, 19 type 2, 17 type 3, three type 4 and 21 type
      5 lesions were identified. The mean (+/-SD) ADC(total), ADC(min) and ADC(max) for
      all lesions were 1.73 +/- 0.50, 0.76 +/- 0.38 and 2.63 +/- 0.76 * 10(-3)mm(2)/s,
      respectively. The mean ADC(total) for type 1, type 2, type 3, type 4 and type 5
      lesions were 1.97 +/- 1.01, 1.76 +/- 0.53, 1.73 +/- 0.41, 1.15 +/- 0.42 and 1.76
      +/- 0.44 * 10(-3)mm(2)/s, respectively. No significant differences were found
      between the five lesion types, except for type 4 (p=0.0363). There was a
      significant correlation between the presence of a solid component and low ADCmin
      (r=0.39, p=0.0016), whereas an inverse correlation was found between the relative
      contrast enhancement and ADCtotal (r=-0.34, p=0.0072). CONCLUSION: The ADCs of AE
      lesions are relatively low compared to other cystic liver lesions, which may help
      in the differential diagnosis. Although ADCs are of little use to distinguish
      between the five lesion types, their low value reflects the underlying solid
      component.

PMID- 24457141
TI  - The Sherlock Holmes method in clinical practice.
AB  - This article lists the integral elements of the Sherlock Holmes method, which is
      based on the intelligent collection of information through detailed observation,
      careful listening and thorough examination. The information thus obtained is
      analyzed to develop the main and alternative hypotheses, which are shaped during
      the deductive process until the key leading to the solution is revealed. The
      Holmes investigative method applied to clinical practice highlights the
      advisability of having physicians reason through and seek out the causes of the
      disease with the data obtained from acute observation, a detailed review of the
      medical history and careful physical examination.

PMID- 24457142
TI  - Name change for schizophrenia.

PMID- 24457143
TI  - Respiratory protection policies and practices among the health care workforce
      exposed to influenza in New York State: evaluating emergency preparedness for the
      next pandemic.
AB  - BACKGROUND: New York State hospitals are required to implement a respiratory
      protection program (RPP) consistent with the Occupational Safety and Health
      Administration respirator standard. Guidance provided during the 2009 novel H1N1
      pandemic expanded on earlier recommendations, emphasizing the need to keep staff
      in all health care settings healthy to maintain services. METHODS: New York State
      hospitals with emergency departments having more than 1,000 visits annually were
      invited to participate; 23 hospitals participated. Health care workers, unit
      managers, and hospital managers were interviewed regarding knowledge, beliefs,
      and practices of respiratory protection. Interviewees were observed donning and
      doffing an N-95 respirator as they normally would during patient care. Written
      RPPs for each hospital were evaluated. RESULTS: The majority of the hospitals
      surveyed had implemented an RPP, although unawareness of the policies and
      practices, as well as inadequacies in education and training exist among health
      care workers. CONCLUSION: Health care workers and other hospital employees may be
      unnecessarily exposed to airborne infectious diseases. Having an RPP ensures safe
      and effective use of N-95 respirators and will help prevent avoidable exposure to
      disease during a pandemic, protecting the health care workforce and patients
      alike.

PMID- 24457144
TI  - A double-blind, randomized, controlled study to explore the efficacy of rFVIIa on
      intraoperative blood loss and mortality in patients with severe acute
      pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis is a life-threatening disease. Patients
      with peripancreatic necrotic infection often require surgical removal of necrotic
      infected tissue and a wide debridement will cause blood loss and worsen the
      condition. AIM: To assess whether treatment with NovoSeven, a recombinant
      activated FVII (rFVIIa), could improve coagulation function and therefore reduce
      blood loss, blood transfusion and all-cause mortality during necrosectomy in
      patients with infected necrosis secondary to severe acute pancreatitis. MATERIALS
      AND METHODS: Severe acute pancreatitis patients admitted to Nanjing Jinling
      Hospital for necrosectomy were enrolled and randomized to receive either standard
      treatment or standard treatment plus an intravenous infusion of rFVIIa (40MUg per
      kilogram of body weight per hour) before operation. The prospectively defined
      primary end points were perioperative coagulation parameters (prothrombin time,
      activated partial thromboplastin time), blood transfusion unit and blood loss.
      The secondary end points were operation time, ICU stay and all-cause mortality at
      28days after the operation. RESULTS: A total of 64 patients were enrolled (31 in
      the rFVIIa group and 33 in the control group). Treatment with rFVIIa was
      associated with a reduction in operation time, red blood cell and fresh froze
      plasma transfusion, blood loss and prothrombin time compared to the control group
      (p<0.05 for all). Activated partial thromboplastin time and mortality were
      similar between the two groups (P>0.05). CONCLUSION: Treatment with rFVIIa
      significantly improved the extrinsic coagulation function in patients with severe
      acute pancreatitis and was associated with decreased risk of bleeding. However,
      rFVIIa did not improve intrinsic coagulation or reduce over-cause mortality.
      CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-1300389.

PMID- 24457145
TI  - Increased risk of deep vein thrombosis and pulmonary thromboembolism in patients
      with spinal cord injury: a nationwide cohort prospective study.
AB  - BACKGROUND: We investigated the effect of spinal cord injury (SCI) on the
      development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) by
      conducting a nationwide longitudinal cohort study. METHODS: We studied the entire
      hospitalized population in Taiwan for the 1998-2008 period, with a follow-up
      period extending to the end of 2010. We identified SCI patients using the Taiwan
      National Health Insurance Research Database (NHIRD), and selected a cohort that
      was 1:4 frequency-matched by age (5-y span), sex, and index year from the general
      population. We analyzed the risks of DVT and PE using Cox proportional-hazards
      regression models, which included the demographic variables of sex, age, and
      comorbidities. RESULTS: A total of 47,916 SCI patients (62.7% men, mean age of
      50.0 y) and 191,664 controls were followed for 308,266 and 1,341,169 person
      years, respectively. The adjusted hazard ratio (HR) of DVT and PE development was
      2.46-fold and 1.57-fold among the SCI patients, respectively. The highest risk of
      DVT and PE developed within 3months after an SCI occurred (HR: 16.9 and 3.64,
      respectively). The adjusted HR of DVT and PE rose markedly with increasing age.
      The adjusted HR of DVT was highest among C-spine SCI patients, and the adjusted
      HR of PE was highest among T-spine SCI patients. CONCLUSION: This nationwide
      prospective cohort study demonstrated that the risk of DVT and PE increased
      significantly in SCI patients compared with that of the general population. The
      highest risk of DVT and PE developed within 3months after an SCI occurred.

PMID- 24457146
TI  - An Updated Therapeutic Intervention Scoring System for Critically Ill Children
      Enables Nursing Workload Assessment With Insight Into Potential Untoward Events.
AB  - BACKGROUND: To introduce an updated version of the original Therapeutic
      Intervention Scoring System (TISS) applicable to critically ill children (TISS
      C). This version was designed to assess patient acuity and nursing workload (NW)
      and to determine a relationship between such assessment and the incidence of
      adverse events. METHODS: Reviewing previous versions of TISS, an updated TISS-C
      was developed. Items inapplicable to pediatric critical care were eliminated;
      items current to critical care were added; and items still valid were edited. The
      point system accounts for the wide range of care provided. Random patients from a
      predetermined period had TISS-C scores calculated. The TISS-C scores were also
      calculated on patients with documented adverse events. Baseline scores were
      compared with scores of patients in whom adverse events had occurred. We
      determined the pediatric intensive care unit (PICU) NW to be the product of the
      TISS-C score and the patient-nurse ratio (PNR). RESULTS: One hundred twenty-five
      random patients had a mean TISS-C of 14.6 +/- 11.8. Patients with any adverse
      event (98) had a TISS-C of 19.9 +/- 11.6 (P < .05). Using our PICU mean PNR of
      1.4 (20 patients/14 nurses), the NW for patients with more severe events was 33.6
      +/- 15.9. CONCLUSIONS: Critically ill pediatric patients are more vulnerable to
      experience adverse events when their derived NW values are high. It is postulated
      that a critical NW exists, where adverse events are more likely to occur.

PMID- 24457147
TI  - Replicative Capacity of MERS Coronavirus in Livestock Cell Lines.
AB  - Replicative capacity of Middle East respiratory syndrome coronavirus (MERS-CoV)
      was assessed in cell lines derived from livestock and peridomestic small mammals
      on the Arabian Peninsula. Only cell lines originating from goats and camels
      showed efficient replication of MERS-CoV. These results provide direction in the
      search for the intermediate host of MERS-CoV. 

PMID- 24457148
TI  - Evaluation of gelatin hydrogel as a potential carrier for cell transportation.
AB  - We prepared uncleaved gelatin composed mainly of collagen alpha-, beta-, and
      gamma-chains. Gelation and melting of uncleaved gelatin occurred rapidly with
      moderate decrease and increase in temperature (23 degrees C-37 degrees C). The
      viability of cells encapsulated in the gelatin gel was greater than 96% after 7 d
      at 23 degrees C.

PMID- 24457150
TI  - Intravitreal ranibizumab (lucentis) for whole brain radiotherapy-induced
      maculopathy.

PMID- 24457149
TI  - Effect of Ca(2+) on the activity and structure of alpha-glucosidase: inhibition
      kinetics and molecular dynamics simulations.
AB  - Understanding the mechanism of inhibition of alpha-glucosidase (EC 3.2.1.20) is
      clinically important because of the involvement of this enzyme in type 2 diabetes
      mellitus. In this study, we conducted inhibition kinetics of alpha-glucosidase
      with Ca(2+) and 10-ns molecular dynamics simulations. We found that direct
      binding of Ca(2+) to the enzyme induced structural changes and inhibited enzyme
      activity. Ca(2+) inhibited alpha-glucosidase in a mixed-type reaction (Ki = 27.0
      +/- 2.0 mM) and directly induced the unfolding of alpha-glucosidase, which
      resulted in the exposure of hydrophobic residues. The simulations suggest that
      thirteen Ca(2+) ions may interact with alpha-glucosidase residues and that the
      Ca(2+) binding sites are associated with the structural changes in alpha
      glucosidase. Our study provides insight into the mechanism of the Ca(2+)-induced
      structural changes in alpha-glucosidase and the inhibition of ligand binding.
      These results suggest that Ca(2+) could act as a potent inhibitor of alpha
      glucosidase for the treatment of type 2 diabetes mellitus. 

PMID- 24457152
TI  - Thermal fluctuation based study of aqueous deficient dry eyes by non-invasive
      thermal imaging.
AB  - In this paper we have studied the thermal fluctuation patterns occurring at the
      ocular surface of the left and right eyes for aqueous deficient dry eye (ADDE)
      patients and control subjects by thermal imaging. We conducted our experiment on
      42 patients (84 eyes) with aqueous deficient dry eyes and compared with 36
      healthy volunteers (72 eyes) without any history of ocular surface disorder.
      Schirmer's test, Tear Break-up Time, tear Meniscus height and fluorescein
      staining tests were conducted. Ocular surface temperature measurement was done,
      using an FL-IR thermal camera and thermal fluctuation in left and right eyes was
      calculated and analyzed using MATLAB. The time series containing the sum of
      squares of the temperature fluctuation on the ocular surface were compared for
      aqueous deficient dry eye and control subjects. Significant statistical
      difference between the fluctuation patterns for control and ADDE was observed (p
      < 0.001 at 95% confidence interval). Thermal fluctuations in left and right eyes
      are significantly correlated in controls but not in ADDE subjects. The possible
      origin of such correlation in control and lack of correlation in the ADDE
      subjects is discussed in the text. 

PMID- 24457151
TI  - Nicotine shifts the temporal activation of hippocampal protein kinase A and
      extracellular signal-regulated kinase 1/2 to enhance long-term, but not short
      term, hippocampus-dependent memory.
AB  - Acute nicotine enhances hippocampus-dependent learning through nicotine binding
      to beta2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear
      if nicotine is targeting processes involved in short-term memory (STM) leading to
      a strong long-term memory (LTM) or directly targeting LTM. In addition, the
      molecular mechanisms involved in the effects of nicotine on learning are unknown.
      Previous research indicates that protein kinase A (PKA), extracellular signal
      regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM.
      Therefore, the present study examined the effects of nicotine on STM and LTM and
      the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced
      enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The
      protein synthesis inhibitor anisomycin impaired contextual conditioning assessed
      at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM
      (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but
      not 2 h post-training, indicating nicotine specifically enhances LTM but not STM.
      Furthermore, nicotine did not rescue deficits in contextual conditioning produced
      by anisomycin, suggesting that the nicotine enhancement of contextual
      conditioning occurs through a protein synthesis-dependent mechanism. In addition,
      inhibition of dorsal hippocampal PKA activity blocked the effect of acute
      nicotine on learning, and nicotine shifted the timing of learning-related PKA and
      ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results
      suggest that nicotine specifically enhances LTM through altering the timing of
      PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA
      and ERK1/2 activity could contribute to the strength of memories.

PMID- 24457153
TI  - Ginkgolic acids and Ginkgo biloba extract inhibit Escherichia coli O157:H7 and
      Staphylococcus aureus biofilm formation.
AB  - Infection by enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a worldwide
      problem, and there is no effective therapy. Biofilm formation is closely related
      to EHEC infection and is also a mechanism of antimicrobial resistance.
      Antibiofilm screening of 560 purified phytochemicals against EHEC showed that
      ginkgolic acids C15:1 and C17:1 at 5MUg/ml and Ginkgo biloba extract at 100MUg/ml
      significantly inhibited EHEC biofilm formation on the surfaces of polystyrene and
      glass, and on nylon membranes. Importantly, at their working concentrations,
      ginkgolic acids and G. biloba extract did not affect bacterial growth.
      Transcriptional analyses showed that ginkgolic acid C15:1 repressed curli genes
      and prophage genes in EHEC, and these findings were in-line with reduced fimbriae
      production and biofilm reductions. Interestingly, ginkgolic acids and G. biloba
      extract did not inhibit the biofilm formation of a commensal E. coli K-12 strain.
      In addition, ginkgolic acids and G. biloba extract inhibited the biofilm
      formation of three Staphylococcus aureus strains. The findings of this study
      suggest that plant secondary metabolites represent an important resource for
      biofilm inhibitors. 

PMID- 24457154
TI  - The tissue engineer's toolbox manifesto.

PMID- 24457155
TI  - Understanding structural and functional aspects of PII snake venom
      metalloproteinases: characterization of BlatH1, a hemorrhagic dimeric enzyme from
      the venom of Bothriechis lateralis.
AB  - A new homodimeric PII metalloproteinase, named BlatH1, was purified from the
      venom of the Central American arboreal viperid snake Bothriechis lateralis by a
      combination of anion-exchange chromatography, hydrophobic interaction
      chromatography, and gel filtration. BlatH1 is a glycoprotein of 84 kDa. The
      mature protein contains a metalloproteinase domain, with the characteristic zinc
      binding motif (HEXXHXXGXXH) followed by the sequence CIM at the Met-turn. In the
      disintegrin domain, the tripeptide sequence TDN substitutes the characteristic
      RGD motif found in many disintegrins. BlatH1 hydrolyzed azocasein, gelatin and
      fibrinogen, and exerts a potent local and systemic hemorrhagic activity in mice.
      The hemorrhagic activity of BlatH1 is not inhibited by the plasma proteinase
      inhibitor alpha2-macroglobulin, although the SVMP is able to cleave this plasma
      inhibitor, generating a 90 kDa product. BlatH1 inhibits ADP- and collagen-induced
      human platelet aggregation (IC50 = 0.3 MUM and 0.7 MUM for ADP and collagen,
      respectively). This activity is abrogated when the enzyme is preincubated with
      the metalloproteinase inhibitor Batimastat, implying that it depends on
      proteolysis. In agreement, a synthetic peptide containing the sequence TDN of the
      disintegrin domain is unable to inhibit platelet aggregation. BlatH1 is a
      valuable tool to understand the structural determinants of toxicity in PII SVMPs.

PMID- 24457156
TI  - Effectiveness of diathermy in comparison with ultrasound or corticosteroids in
      patients with tendinopathy: a critically appraised topic.
AB  - CLINICAL SCENARIO: Many therapeutic modalities have been used to treat the pain
      and inflammation commonly associated with tendinopathies. One modality that has
      been used to treat patients with tendinopathies is diathermy. FOCUSED CLINICAL
      QUESTION: Is there evidence to suggest that diathermy is more or equally as
      effective at reducing pain in patients with tendinopathy when compared with
      ultrasound or corticosteroid treatments? SUMMARY OF SEARCH, "BEST EVIDENCE"
      APPRAISED, AND KEY FINDINGS: The literature was searched for randomized control
      trials (RCTs) that investigated the effects of diathermy treatments in comparison
      with ultrasound or corticosteroid treatments on pain in patients with
      tendinopathy. Three RCTs were selected from the search results and included in
      this critically appraised topic. CLINICAL BOTTOM LINE: There is moderate evidence
      to support that diathermy is more effective at reducing pain in patients with
      tendinopathy than ultrasound and equally as effective as corticosteroid
      treatments. STRENGTH OF RECOMMENDATION: There is grade B evidence to support that
      diathermy is more effective at reducing pain in patients with tendinopathy than
      ultrasound and equally effective at reducing pain as corticosteroid treatments.

PMID- 24457158
TI  - Necrotizing hepatitis in a domestic pigeon (Columba livia).
AB  - An adult male domestic pigeon (Columba livia) was presented for necropsy
      following natural death after a period of chronic weight loss and severe
      intestinal ascariasis. Histopathologic examination of the liver found moderate to
      marked, multifocal necrotizing hepatitis with large, basophilic intranuclear
      inclusion bodies. Transmission electron microscopy of affected hepatocytes
      demonstrated numerous intra- and perinuclear icosahedral virions arranged in a
      lattice structure, consistent with adenoviral infection. 

PMID- 24457157
TI  - Megaesophagus in a line of transgenic rats: a model of achalasia.
AB  - Megaesophagus is defined as the abnormal enlargement or dilatation of the
      esophagus, characterized by a lack of normal contraction of the esophageal walls.
      This is called achalasia when associated with reduced or no relaxation of the
      lower esophageal sphincter (LES). To date, there are few naturally occurring
      models for this disease. A colony of transgenic (Pvrl3-Cre) rats presented with
      megaesophagus at 3 to 4 months of age; further breeding studies revealed a
      prevalence of 90% of transgene-positive animals having megaesophagus. Affected
      rats could be maintained on a total liquid diet long term and were shown to
      display the classic features of dilated esophagus, closed lower esophageal
      sphincter, and abnormal contractions on contrast radiography and fluoroscopy.
      Histologically, the findings of muscle degeneration, inflammation, and a reduced
      number of myenteric ganglia in the esophagus combined with ultrastructural
      lesions of muscle fiber disarray and mitochondrial changes in the striated muscle
      of these animals closely mimic that seen in the human condition. Muscle
      contractile studies looking at the response of the lower esophageal sphincter and
      fundus to electrical field stimulation, sodium nitroprusside, and L-nitro-L
      arginine methyl ester also demonstrate the similarity between megaesophagus in
      the transgenic rats and patients with achalasia. No primary cause for
      megaesophagus was found, but the close parallel to the human form of the disease,
      as well as ease of care and manipulation of these rats, makes this a suitable
      model to better understand the etiology of achalasia as well as study new
      management and treatment options for this incurable condition. 

PMID- 24457159
TI  - Mirror sniffing: humans mimic olfactory sampling behavior.
AB  - Ample evidence suggests that social chemosignaling plays a significant role in
      human behavior. Processing of odors and chemosignals depends on sniffing. Given
      this, we hypothesized that humans may have evolved an automatic mechanism driving
      sniffs in response to conspecific sniffing. To test this, we measured sniffing
      behavior of human subjects watching the movie Perfume, which contains many
      olfactory sniffing events. Despite the total absence of odor, observers sniffed
      when characters in the movie sniffed. Moreover, this effect was most pronounced
      in scenes where subjects heard the sniff but did not see the sniffed-at object.
      We liken this response to the orienting towards conspecific gaze in vision and
      argue that its robustness further highlights the significance of olfactory
      information processing in human behavior. 

PMID- 24457160
TI  - Signal and contrast effects due to T2 decay during k-space readout of UTE
      (ultrashort TE) sequences.
AB  - In ultrashort TE (UTE) imaging, the short T2 values of the tissues of interest
      are comparable to the k-space readout duration, which result in significant T2
      decay during k-space readout. This decay consequently causes significant effects
      on signal and contrast in UTE sequences, which we evaluate in this paper using
      models that incorporate the gradient slew rate slew and maximal constant gradient
      strength gmax, in conjunction with objects of diameter L. The resulting signal
      and contrast relationships demonstrate steep signal changes between T2 values of
      ~50-500MUs, corresponding to high T2 weighted contrast in this range. When
      gamma?gmax(2)/(4pi?slew)>1/(2L), termed the "ramp only" regime, gmax has no
      significant effect whereas decreasing slew leads to decreases in signal amplitude
      and shifts the contrast peak to higher T2 values. When
      gamma?gmax(2)/(4pi?slew)<1/(2L), termed the "mixed gradient" regime, both gmax
      and slew have significant effects, where decreases in either gmax or slew lead to
      lower signal amplitudes and shifts the contrast peak to higher T2 values. Under
      typical scan settings, the "ramp only" regime is usually dominant. Further, we
      demonstrate an unusual dependence of T2 weighted signal and contrast on object
      size, whereby objects with smaller values of L demonstrate lower signal
      amplitudes and peak contrast at higher T2 values, compared to otherwise identical
      objects with larger L. These results improve understanding of T2 weighted signal
      and contrast properties in short T2 tissue imaging with UTE. 

PMID- 24457161
TI  - IGFBP-3 promoter polymorphism -202A>C (rs2854774) contributes to prostate cancer
      risk: evidence based on 9,482 subjects.
AB  - OBJECTIVE: Evidence suggests that insulin-like growth factor-binding protein 3
      (IGFBP-3) might play a role in the carcinogenesis of prostate cancer (PCa). To
      date, several studies have been conducted to investigate the association between
      IGFBP-3 -202A>C polymorphism and PCa risk in humans. However, the results remain
      inconclusive and inconsistent. Hence, we performed a meta-analysis of all
      eligible case-control studies. METHODS: We used odds ratios (ORs) with 95%
      confidence intervals (CIs) to assess the strength of the association. RESULTS: 16
      studies from 10 articles that included a total of 4,602 PCa cases and 4,880
      controls were included in the meta-analysis. The results showed that the IGFBP-3 
      A>C polymorphism was associated with a significant increase in PCa risk. The
      variant homozygote genotype CC of IGFBP-3 -202A>C polymorphism was associated
      with a significantly increased risk in homozygote comparison (OR = 1.22, 95% CI =
      1.07-1.38, I(2) = 36.10%) and recessive model (OR = 1.11, 95% CI = 1.00-1.22,
      I(2) = 15.60%). In the stratified analysis, the risk remained for studies in
      Asian men and hospital-based studies. CONCLUSIONS: These results suggested that
      the IGFBP-3 -202A>C polymorphism might contribute to PCa susceptibility,
      especially in Asian men and hospital-based studies. Further studies are needed to
      confirm the relationship.

PMID- 24457163
TI  - Progress in tackling malaria.

PMID- 24457162
TI  - Who is at risk for having persistent insomnia symptoms? A longitudinal study in
      the general population in Korea.
AB  - OBJECTIVES: Our study had three goals: (1) to investigate the longitudinal course
      of insomnia symptoms over 4 years (3 time points) by analyzing the trajectory of
      insomnia symptoms for all participants, (2) to compare persistent insomnia
      symptom to nonpersistent insomnia symptom groups on mental health and quality of
      life (QoL), and (3) to conduct exploratory analyses on the relative contribution
      of multiple factors to persistence of insomnia symptoms. METHODS: Our population
      based longitudinal study utilized a community-based sample from the Korean Genome
      and Epidemiology study (KoGES). Participants were 1247 individuals (40.1% men;
      mean age, 54.3+/-7.1 years). Insomnia, QoL (measured by 12-item Short-Form health
      survey [SF-12]), sleep-interfering behaviors, and depression (measured by the
      Beck Depression Inventory [BDI]) were followed with biennial examinations at 3
      data points spaced 2 years apart (baseline, time 1, and time 2). RESULTS: Among
      individuals experiencing insomnia symptoms at baseline, the most common
      trajectory was to experience persistent nocturnal insomnia symptoms across all 3
      time points. Those with persistent insomnia symptoms had significantly lower
      physical and mental QoL (measured by SF-12) and higher depression (measured by
      BDI) at time points compared to those without persistent nocturnal insomnia
      symptoms. A follow-up exploratory receiver operating characteristic curve (ROC)
      analysis identified poor sleep quality, frequent sleep-interfering behaviors, and
      low mental health QoL as the strongest predictors of persistent insomnia symptoms
      above other well-known risk factors. CONCLUSIONS: In particular, an interaction
      between poor sleep quality, sleep-interfering behaviors, and mental health QoL
      appeared to be the strongest risk factor for persistent insomnia symptoms.

PMID- 24457164
TI  - Molecular identification of staphylococcal bacteraemia.

PMID- 24457165
TI  - A strategy to halt leprosy transmission.

PMID- 24457166
TI  - Predicting the potential for within-flight transmission and global dissemination
      of MERS.

PMID- 24457167
TI  - DPP4-directed therapeutic strategies for MERS-CoV.

PMID- 24457168
TI  - Missing information in animal surveillance of MERS-CoV.

PMID- 24457169
TI  - Age and different influenza viruses.

PMID- 24457170
TI  - Effects of glass bead size, vortexing speed and duration on Eimeria acervulina
      oocyst excystation.
AB  - Improved methods for efficient excystation of Eimeria should be developed and
      standardized for future Eimeria-related studies. Here, the effects of different
      glass bead sizes (0.5, 1, 2, and 2.5 mm), and various vortex speeds (1000, 2000,
      and 3000 rpm) and durations (30 s, 1, 3, and 5 min) have been examined for
      Eimeria (E.) acervulina oocyst excystation. At 3000 rpm, all glass beads,
      regardless of size, efficiently ruptured E. acervulina oocysts at 5 min. At 2000
      and 3000 rpm, all four glass bead sizes increasingly ruptured oocysts in a time
      dependent manner. In contrast, at 1000 rpm the excystation efficiency was not
      related with the glass bead size or with vortexing duration. It appeared that the
      1mm glass beads are most efficient for E. acervulina DNA extraction at a 3000 rpm
      vortexing speed for 3 and 5 min. The 2 mm glass beads delicately released the
      highest number of intact sporocysts at 2000 rpm for 3 min. Therefore, our data
      can provide valuable information for the efficient mechanical excystation of E.
      acervulina.

PMID- 24457172
TI  - Green fabrication of quaternized chitosan/rectorite/Ag NP nanocomposites with
      antimicrobial activity.
AB  - Silver nanoparticles (Ag NPs) were synthesized rapidly in one pot via the Tollens
      reaction, in which quaternized chitosan (QCS) and rectorite (REC) acted as the
      reducing and stabilizing agent, while other chemical reducing and stabilizing
      agents and the surfactant were not included. X-ray diffraction, scanning electron
      microscopy and transmission electron microscopy results showed that spherical Ag
      NPs with uniform sizes were obtained, the layers of clay were peeled and thus
      exfoliated QCS/REC/Ag NP (QCRAg) nanocomposite was achieved. Moreover, Ag NPs
      dispersed well in the exfoliated nanocomposite matrix, some Ag NPs even entered
      into the interlayer of REC. QCRAg nanocomposites showed strong antimicrobial
      activity; the lowest minimum inhibitory concentration against Staphyloccocus
      aureus was only 0.0001% (w/v). The study reveals that the obtained QCRAg
      nanocomposites have great potential for biomedical applications. 

PMID- 24457173
TI  - Astrogliosis as a therapeutic target for neurodegenerative diseases.
AB  - Chronic neurodegenerative diseases represent major unmet needs for therapeutic
      interventions. Recently, the neurocentric view of brain function and disease has
      been challenged by a great number of evidence supporting the physiopathological
      potential of neuroglia. Astrocytes, in particular, play a pivotal role in brain
      homeostasis as they actively participate in neuronal metabolism, synaptic
      plasticity and neuroprotection. Furthermore, they are intrinsic components of
      brain responses to toxic and traumatic insults through complex processes
      involving several molecular and functional alterations that may lead to
      disruption of brain homeostasis and connectivity. This review provides a brief
      overview of current knowledge of astrocyte functions in the brain, and focuses on
      some glial-specific pathways involved in astrocytic dysfunction that might be
      effective therapeutic targets for clinical management of neurodegenerative
      disorders. 

PMID- 24457174
TI  - Preparation of cell blocks for lung cancer diagnosis and prediction: protocol and
      experience of a high-volume center.
AB  - Minimally invasive diagnostic techniques are increasingly being used to obtain
      specimens for pathological diagnosis and prediction. Referring to lung cancer,
      both endobronchial and endoesophageal ultrasound are used worldwide as diagnostic
      routine methods. Consequently, an increasing number of pathological samples are
      cytological and fewer are histological. On the other hand, the requirements for
      specific and sensitive tumor subtyping complemented by predictive analyses are
      steadily increasing and are an essential basis for evidence-based treatment
      decisions. In this article we focus on the cell block method as a helpful tool
      for diagnostic and predictive analyses in lung cancer and point out its
      advantages and disadvantages in comparison to conventional cytological and biopsy
      specimens. Furthermore, we retrospectively analyze the diagnostic results of the
      cell block method in a high-volume center over 5 years. The main advantages of
      cell blocks are the availability of established and validated protocols,
      archiving and the opportunity to have serial sections from the same specimens to
      provide or repeat molecular analyses. Actually, in case of tumor progression,
      even additional biomarkers can be tested using the original cell block when re
      biopsies are not feasible. The cell block method should be considered as a
      reliable, complimentary approach to conventional cytological or biopsy
      procedures, which is helpful to fulfill the increasing requirements of high
      quality diagnostics and prediction.

PMID- 24457175
TI  - Healthcare providers' awareness of the information needs of their cardiac
      rehabilitation patients throughout the program continuum.
AB  - OBJECTIVE: To (1) describe cardiac rehabilitation (CR) participant information
      needs, (2) investigate whether CR providers are cognizant of patient's
      information needs and preferred delivery formats, and (3) investigate whether
      patient information needs change over the course of CR. METHODS: In this cross
      sectional study, 306 CR patients and 28 CR providers completed a survey. The
      survey consisted of the Information Needs in CR (INCR) questionnaire, and items
      about preferred education delivery formats. RESULTS: Low-income CR participants
      had significantly greater information needs than high-income participants. CR
      providers were cognizant of patient information needs, except patients did desire
      more information on diagnosis and treatment than providers perceived (p<0.01).
      Books, lectures and discussion were identified as the preferred delivery formats
      by both patients and providers. There were some significant differences in
      patient information needs over the course of the program, particularly in
      relation to concerns and risk factors. CONCLUSION: CR patients desire information
      in many areas, particularly regarding emergency/safety and diagnosis/treatment.
      CR providers were highly cognizant of patient information needs; however, these
      do change over time. PRACTICE IMPLICATIONS: These findings could inform
      evaluation and improvement of CR education programming, to ensure programs are
      meeting patient information needs across all stages of recovery.

PMID- 24457176
TI  - Frequency and pattern of rhythmic leg movement in humans after fatiguing
      exercises.
AB  - In the current study we investigated changes in voluntary rhythmic leg movement
      frequency (freely chosen cycling cadence) and rhythmic movement pattern
      (tangential pedal force profile) after fatiguing hip flexion and hip extension
      exercises. Nine healthy individuals performed ergometer cycling at freely chosen
      cadence and at a cadence of 1 Hz before and after fatiguing hip flexion and hip
      extension exercises. The freely chosen cadence was not affected after fatiguing
      exercises. An alteration of key characteristics of the tangential pedal force
      profile was found during cycling at a cadence of 1 Hz after hip flexion exercise.
      Thus, minimum tangential pedal force decreased by 12.0 +/- 11.3% (p = .006),
      while maximum tangential pedal force increased by 4.6 +/- 4.2% (p = .011), and
      the phase with negative tangential pedal force increased by 2.6 +/- 3.2% (p =
      .040). In conclusion, novel information was obtained on aspects of rhythmic leg
      movement behavior in form of pedaling after fatiguing exercise. 

PMID- 24457177
TI  - Effects of perforator number and location on the total pedicle flow and perfusion
      of zone IV skin and fat of DIEP flaps by Douglas et al.

PMID- 24457178
TI  - [Use of methadone in the elderly with cancer pain: a systematic review].
AB  - OBJECTIVE: To identify the clinical use of methadone as an analgesic in the
      management of cancer pain in elderly patients. MATERIAL AND METHODS: We performed
      a systemic review of the literature on the specific use of methadone in elderly
      with cancer pain in MEDLINE, COCHRANE DATABASE and SCOPUS. A second search was
      conducted in MEDLINE to look for clinical trials and systematic review of the use
      of methadone in cancer pain, selecting only those in which the mean age of
      patients was >= 65 years old. RESULTS: Four articles were obtained in the first
      search, and from the second 7 clinical trials, none of them specific to methadone
      use in elderly patients with cancer. CONCLUSIONS: There are insufficient data on
      the use of methadone as an analgesic in the elderly with cancer. Given its
      pharmacological characteristics it must be used by trained personnel. Several
      recommendations are proposed for its use as an analgesic in the treatment of
      cancer pain in the elderly.

PMID- 24457180
TI  - Intimate partner violence affecting Latina women and their children.

PMID- 24457179
TI  - The effect of an electronic documentation system on the trauma patient's length
      of stay in an emergency department.
AB  - INTRODUCTION: Electronic patient records are important for quality health
      services and efficient patient data management. In emergency care, saving
      valuable time during patient care is of great significance. One out of two
      fatalities due to trauma occur half an hour after the injury. The aim of this
      study was to investigate the potential effect of an electronic trauma
      documentation system on the length of stay in an emergency department. METHODS: A
      2-year observational study was conducted in the emergency department of a
      university hospital located in central Greece. The purpose was to compare 3
      length-of-stay parameters with and without the use of an electronic documentation
      system. Ninety-nine trauma patients were monitored with the use of the electronic
      system, whereas 101 patients were monitored with a paper-based method (control
      group). RESULTS: Statistical analysis using independent-samples t tests indicated
      that the time between admission and completion of the planned care was
      significantly lower in the electronic documentation patient group (100 +/- 92
      minutes) than in the control group (149 +/- 29 minutes) (P < .01). A similar
      effect was found on the total ED length of stay (127 +/- 93 minutes in electronic
      documentation group vs 206 +/- 41 minutes in control group, P < .01) and the time
      between completion of care and discharge from the emergency department (26 +/- 10
      minutes in electronic documentation group vs 57 +/- 23 minutes in control group,
      P < .01). DISCUSSION: We investigated 3 length-of-stay parameters and found that
      all were lower with the use of the electronic documentation system. This finding
      is important regarding the quality of trauma patient care because saving time
      during the first hours after the injury may determine the outcome of the trauma
      patient.

PMID- 24457181
TI  - Partnerships with providers: reflections from parents of children with type 1
      diabetes.
AB  - Sixty-three parents with a child or an adolescent with type 1 diabetes
      participated in this study that focused on what helped them "live well with
      diabetes." Beyond medical expertise, parents described a partnering relationship
      with their provider as one of the factors that supported their efforts to live
      well with diabetes. Parents reported that a partnership was enhanced when the
      provider had the ability to understand the dynamic nature of the journey in
      living with diabetes, connect with their family and set the tone by inviting them
      to openly communicate about all aspects of family life impacting diabetes care,
      recognize when and how the provider may have to assume the role of Captain of the
      Ship in times of need, and empathize and respond therapeutically to intense
      emotions inherent in managing diabetes over time. 

PMID- 24457182
TI  - The phosphoproteome and its physiological dynamics in Staphylococcus aureus.
AB  - Phosphorylation events on proteins during growth and stress/starvation can
      represent crucial regulation processes inside the bacterial cell. Therefore,
      serine, threonine and tyrosine phosphorylation patterns were analyzed by two
      powerful complementary proteomic methods for the human pathogen Staphylococcus
      aureus. Using 2D-gel analysis with a phosphosensitive stain (Pro-Q Diamond) and
      gel-free titanium dioxide based phosphopeptide enrichment, 103 putative
      phosphorylated proteins with successfully mapped 68 different phosphorylation
      sites were found in the soluble proteome of S. aureus. Additionally, in a proof
      of concept study, 8 proteins phosphorylated on arginine residues have been
      identified. Most important for functional analyses of S. aureus, proteins related
      to pathogenicity and virulence were found to be phosphorylated: the virulence
      regulator SarA, the potential antimicrobial target FbaA and the elastin-binding
      protein EbpS. Besides newly identified phosphorylation sites we compared our
      dataset with existing data from literature and subsequent experiments revealed
      additional phosphorylation events on highly conserved localizations in FbaA.
      Differential analysis of phosphorylation signals on the 2D-gels showed
      significant changes in phosphorylation under different physiological conditions
      for 10 proteins. Among these, we were able to detect newly appearing signals for
      phosphorylated isoforms of FdaB and HchA under nitrosative stress conditions. 

PMID- 24457183
TI  - Clp chaperones and proteases are central in stress survival, virulence and
      antibiotic resistance of Staphylococcus aureus.
AB  - Intracellular proteolysis carried out by energy-dependent proteases is one of the
      most conserved biological processes. In all cells proteolysis maintains and
      shapes the cellular proteome by ridding the cell of damaged proteins and by
      regulating abundance of functional proteins such as regulatory proteins. The ATP
      dependent ClpP protease is highly conserved among eubacteria and in the
      chloroplasts and mitochondria of eukaryotic cells. In the serious human pathogen,
      Staphylococcus aureus inactivation of clpP rendered the bacterium avirulent
      emphasizing the central role of proteolysis in virulence. The contribution of the
      Clp proteins to virulence is likely to occur at multiple levels. First of all,
      both Clp ATPases and the Clp protease are central players in stress responses
      required to cope with the adverse conditions met in the host. The ClpP protease
      has a dual role herein, as it both eliminates stress-damaged proteins as well as
      ensures the timely degradation of major stress regulators such as Spx, LexA and
      CtsR. Additionally, as we will summarize in this review, Clp proteases and Clp
      chaperones impact on such central processes as virulence gene expression, cell
      wall metabolism, survival in stationary phase, and cell division. These
      observations together with recent findings that Clp proteins contribute to
      adaptation to antibiotics highlights the importance of this interesting
      proteolytic machinery both for understanding pathogenicity of the organism and
      for treating staphylococcal infections. 

PMID- 24457185
TI  - On the non-linear attachment characteristics of blood to bacterial
      cellulose/kaolin biomaterials.
AB  - In this communication, we report a non-linear variation in the strength of blood
      attachment to bacterial cellulose/kaolin biomaterials as the fractions of
      bacterial cellulose to kaolin are increased. The changes observed for attachment
      strength are elucidated following both experimental and numerical investigations
      on both the biomaterial and the blood-biomaterial interface. Our research reveals
      that the non-linear strength of attachment of blood is related to topographical
      characteristics on the surface of the biomaterial, the maleability of the
      biomaterial and the intermolecular strength of attraction between clotted blood
      proteins (fibrinogen) with the cellulose/kaolin components of the biomaterial.

PMID- 24457184
TI  - Cystatin C enhances glomerular filtration rate estimating equations in kidney
      transplant recipients.
AB  - BACKGROUND: The glomerular filtration rate (GFR) estimating equation
      incorporating both cystatin C and creatinine perform better than those using
      creatinine or cystatin C alone in patients with reduced GFR. Whether this
      equation performs well in kidney transplant recipients cross-sectionally, and
      more importantly, over time has not been addressed. METHODS: We analyzed four GFR
      estimating equations in participants of the Angiotensin II Blockade for Chronic
      Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology
      Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI
      Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD
      EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR
      (MDRD)). Iothalamate GFR served as a standard (mGFR). RESULTS: mGFR, serum
      creatinine, and cystatin C shortly after transplant were 56.1 +/- 17.0
      ml/min/1.73 m(2), 1.2 +/- 0.4 mg/dl, and 1.2 +/- 0.3 mg/l respectively. eGFR (CKD
      EPI-Creat+CysC) was most precise (R(2) = 0.50) but slightly more biased than eGFR
      (MDRD); 9.0 +/- 12.7 versus 6.4 +/- 15.8 ml/min/1.73 m(2), respectively. This
      improved precision was most evident in recipients with mGFR >60 ml/min/1.73 m(2).
      For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest
      percentage of estimates falling within 30% of mGFR; 75.8 and 68.9%, respectively.
      Longitudinally, equations incorporating cystatin C most closely paralleled the
      change in mGFR. CONCLUSION: eGFR (CKD-EPI-Creat+CysC) is more precise and
      reflects GFR change over time reasonably well. eGFR (MDRD) had superior
      performance in recipients with mGFR between 30 and 60 ml/min/1.73 m(2).

PMID- 24457186
TI  - The beginning of the end of consistency in AED prescribing?

PMID- 24457187
TI  - Helen Cross: jack of all trades (and master of most).

PMID- 24457188
TI  - Taking a pop at Parkinson.

PMID- 24457190
TI  - Connectivity-based approaches in stroke and recovery of function.
AB  - After focal damage, cerebral networks reorganise their structural and functional
      anatomy to compensate for both the lesion itself and remote effects. Novel
      developments in the analysis of functional neuroimaging data enable us to assess
      in vivo the specific contributions of individual brain areas to recovery of
      function and the effect of treatment on cortical reorganisation. Connectivity
      analyses can be used to investigate the effect of stroke on cerebral networks,
      and help us to understand why some patients make a better recovery than others.
      This systems-level view also provides insights into how neuromodulatory
      interventions might target pathological network configurations associated with
      incomplete recovery. In the future, such analyses of connectivity could help to
      optimise treatment regimens based on the individual network pathology underlying
      a particular neurological deficit, thereby opening the way for stratification of
      patients based on the possible response to an intervention. 

PMID- 24457189
TI  - Rasmussen's encephalitis: clinical features, pathobiology, and treatment
      advances.
AB  - Rasmussen's encephalitis is a rare chronic neurological disorder, characterised
      by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and
      progressive neurological and cognitive deterioration. Neuropathological and
      immunological studies support the notion that Rasmussen's encephalitis is
      probably driven by a T-cell response to one or more antigenic epitopes, with
      potential additional contribution by autoantibodies. Careful analysis of the
      association between histopathology and clinical presentation suggests that
      initial damage to the brain is mediated by T cells and microglia, suggesting a
      window for treatment if Rasmussen's encephalitis can be diagnosed early. Advances
      in neuroimaging suggest that progression of the inflammatory process seen with
      MRI might be a good biomarker in Rasmussen's encephalitis. For many patients,
      families, and doctors, choosing the right time to move from medical management to
      surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only
      cure for seizures, but there are inevitable functional compromises. Decisions of
      whether or when surgery should be undertaken are challenging in the absence of a
      dense neurological deficit, and vary by institutional experience. Further, the
      optimum time for surgery, to give the best language and cognitive outcome, is not
      yet well understood. Immunomodulatory treatments seem to slow rather than halt
      disease progression in Rasmussen's encephalitis, without changing the eventual
      outcome. 

PMID- 24457191
TI  - Mitochondria: hub of injury responses in the developing brain.
AB  - Progress in the field of mitochondrial biology in the past few years has shown
      that mitochondrial activities go beyond bioenergetics. These new aspects of
      mitochondrial physiology and pathophysiology have important implications for the
      immature brain. A picture emerges in which mitochondrial biogenesis, mitophagy,
      migration, and morphogenesis are crucial for brain development and synaptic
      pruning, and play a part in recovery after acute insults. Mitochondria also
      affect brain susceptibility to injury, and mitochondria-directed interventions
      can make the immature brain highly resistant to acute injury. Finally, the
      mitochondrion is a platform for innate immunity, contributes to inflammation in
      response to infection and acute damage, and participates in antiviral and
      antibacterial defence. Understanding of these new aspects of mitochondrial
      function will provide insights into brain development and neurological disease,
      and enable discovery and development of new strategies for treatment. 

PMID- 24457192
TI  - Cortical theta is increased while thalamocortical coherence is decreased in rat
      models of acute and chronic pain.
AB  - Thalamocortical oscillations are critical for sensory perception. Although pain
      is known to disrupt synchrony in thalamocortical oscillations, evidence in the
      literature is controversial. Thalamocortical coherence has been reported to be
      increased in patients with neurogenic pain but decreased in a rat model of
      central pain. Moreover, theta (4 to 8 Hz) oscillations in primary somatosensory
      (S1) cortex are speculated to predict pain in humans. To date, the link between
      pain and network oscillations in animal models has been understudied. Thus, we
      tested the hypothesis that pain disrupts thalamocortical coherence and S1 theta
      power in two rat models of pain. We recorded electrocorticography (ECoG)
      waveforms over S1 and local field potentials (LFP) within ventral posterolateral
      thalamus in freely behaving rats under spontaneous (stimulus-independent) pain
      conditions. Rats received intradermal capsaicin injection (Cap) in the hindpaw,
      followed hours later by chronic constriction injury (CCI) of the sciatic nerve
      lasting several days. Our results show that pain decreases coherence between LFP
      and ECoG waveforms in the 2- to 30-Hz range, and increases ECoG power in the
      theta range. These changes are short-lasting after Cap and longer-lasting after
      CCI. These data might be particularly relevant to preclinical correlates of
      spontaneous pain-like behavior, with potential implications to clinical
      biomarkers of ongoing pain.

PMID- 24457193
TI  - Microablation of collagen-based substrates for soft tissue engineering.
AB  - Noting the abundance and importance of collagen as a biomaterial, we have
      developed a facile method for the production of a dense fibrillar extracellular
      matrix mimicking collagen-elastin hybrids with tunable mechanical properties.
      Through the use of excimer-laser technology, we have optimized conditions for the
      ablation of collagen lamellae without denaturation of protein, maintenance of
      fibrillar ultrastructure and preservation of native D-periodicity. Strengths of
      collagen-elastin hybrids ranged from 0.6 to 13 MPa, elongation at break from 9 to
      70% and stiffness from 2.9 to 94 MPa, allowing for the design of a wide variety
      of tissue specific scaffolds. Further, large (centimeter scale) lamellae can be
      fabricated and embedded with recombinant elastin to generate collagen-elastin
      hybrids. Exposed collagen in hybrids act as cell adhesive sites for rat
      mesenchymal stem cells that conform to ablate waveforms. The ability to modulate
      these features allows for the generation of a class of biopolymers that can
      architecturally and physiologically replicate native tissue. 

PMID- 24457194
TI  - Associations between infants' crying, sleep and cortisol secretion and mother's
      sleep and well-being.
AB  - BACKGROUND: Infants' continuous crying is a challenge both for the child and the
      principal caregiver. However, the links between infants' sleep, crying and
      cortisol secretion and mothers' well-being and sleep have been scarcely
      investigated. The aim of the present study was therefore to examine the link
      between cortisol secretion, crying and sleep of infants characterized by
      infantile colic (IC) and mothers' psychological well-being and own sleep.
      METHODS: Mothers of 24 infants characterized by IC (mean age = 8 weeks, SD = 1.5
      weeks) completed a series of questionnaires regarding the infant's crying and
      sleeping patterns. Infants' sleep was objectively assessed with actigraphs.
      Cortisol secretion was measured by means of saliva samples in the mornings after
      waking. After 4 weeks, infants were assessed once again. Mothers completed
      questionnaires assessing their psychological well-being (depressive symptoms,
      family strain) and sleep. RESULTS: Mothers' psychological well-being and sleep
      was greatly predicted by infants' morning saliva cortisol levels, sleep
      disruptions and crying intensity, whereas infants' crying duration and volume had
      low predictive value. CONCLUSIONS: Mothers with infants characterized by IC are
      at increased risk for reporting impaired sleep, developing depressive symptoms
      and reporting higher family strain. Most importantly, this risk seems to be
      greater if their infants' sleep is fragmented.

PMID- 24457195
TI  - Consistency of Bordetella pertussis vaccine seed strains and potency of whole
      cell pertussis vaccine still in use in Poland.
AB  - In Poland, where the wP vaccine has been used since 1960, pertussis rates
      increased in the mid-1990s. In 2012, the rate of pertussis recognised by
      surveillance was unexpectedly found to be two-fold higher than in the previous
      decade. Quality measures on potency and vaccine working seeds were introduced, to
      confirm the possible impact of manufacturing inconsistency or potency lowering on
      the observed increase in pertussis. Shewhart charts on potency values for lots
      released between 2001 and 2013 did not reveal any significant fluctuations.
      Working seeds of three vaccine strains used within last decade for wP
      manufacturing belong to the PFGE group III and were highly related. According to
      PFGE and SDS-PAGE data, all vaccine strains were found consistent according
      profiling on the genomic and protein levels. According to the sequencing data,
      they harboured ptxA2, ptxC1, prn1, fim2-1, fim3-1, tcfA2, ptxP1 and were assigned
      as MLST-2 type. Other factors apart from vaccine manufacturing inconsistency
      might be responsible for the increase in pertussis noted in 2012 in Poland. 

PMID- 24457196
TI  - Cartilage derived morphogenetic protein 2 - a potential therapy for
      intervertebral disc regeneration?
AB  - Low back pain is amongst the top ten risk factors that contribute to disability,
      ranking higher than diabetes and mental health disease globally as a contributor
      to years lost to disability (YLD), and escalating as Western societies age.
      Abundant evidence suggests that intervertebral disc (IVD) damage is central to
      the origin of pain in the spine. IVD degeneration involves the progressive
      deterioration of the highly organized disc tissue extracellular matrix, losing
      its elasticity and hence its' cushioning ability for the spine. Cartilage derived
      morphogenetic protein-2 (CDMP2) is a small peptide morphogen. Naturally occurring
      mutations segregate with skeletal defects in IVD development. CDMP2 signalling
      influences chondrogenic tissue determination, retards osteogenic tissue
      development and is crucial to early dorso-ventral axis defining events in
      zebrafish and Xenopus laevis. The potential of biological treatments to offer
      cutting edge early intervention, tissue regeneration and to preserve spinal
      motion segments shows great promise. The unique qualities of CDMP2 in IVD tissue
      formation, delineating discal matrix from vertebral bone, may prove adaptable in
      therapeutic applications to early discal degeneration. Here we explore the
      prevalence and origin of backache, the biology of CDMP2 and its potential
      application as an early intervention to arrest the disc degeneration sequelae. 

PMID- 24457197
TI  - A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular
      malformation.
AB  - BACKGROUND: Heterozygous SOX2 mutations have been reported to cause isolated
      hypogonadotropic hypogonadism (HH) in addition to ocular and brain abnormalities.
      OBJECTIVE: We report a novel missense SOX2 (Y110C) mutation in an HH patient with
      mild ocular malformation. PATIENTS: The 20-year-old male was referred because of
      typical signs of complete hypogonadism, with small intrascrotal testes (2 ml), no
      pubic hair (P1), and a micropenis. Hormone assays revealed very low plasma
      testosterone levels and very low levels of plasma gonadotropin. He was found to
      have retinal detachment in his right eye and surgery was performed at the age of
      14 years. RESULTS: Using a next-generation sequencing strategy, we identified a
      novel heterozygous SOX2 mutation, c.329A>G (p.Y110C). Y110C SOX2 had reduced
      transactivation and no dominant negative effect. Subcellular localization
      revealed no significant difference between wild-type and mutant SOX2. EMSA
      experiments showed that the Y110C SOX2 abrogated DNA-binding ability. CONCLUSION:
      The Y110C mutation affects a critical residue in the SOX2 protein. This study
      extends our understanding of the phenotypic features, molecular mechanism, and
      developmental course associated with mutations in SOX2. When multiple genes need
      to be analyzed for mutations simultaneously, targeted sequence analysis of
      interesting genomic regions is an attractive approach.

PMID- 24457198
TI  - Connexins, gap junctions and tissue invasion.
AB  - Formation of metastases negatively impacts the survival prognosis of cancer
      patients. Globally, if the various steps involved in their formation are
      relatively well identified, the molecular mechanisms responsible for the
      emergence of invasive cancer cells are still incompletely resolved. Elucidating
      what are the mechanisms that allow cancer cells to evade from the tumor is a
      crucial point since it is the first step of the metastatic potential of a solid
      tumor. In order to be invasive, cancer cells have to undergo transformations such
      as down-regulation of cell-cell adhesions, modification of cell-matrix adhesions
      and acquisition of proteolytic properties. These transformations are accompanied
      by the capacity to "activate" stromal cells, which may favor the motility of the
      invasive cells through the extracellular matrix. Since modulation of gap
      junctional intercellular communication is known to be involved in cancer, we were
      interested to consider whether these different transformations necessary for the
      acquisition of invasive phenotype are related with gap junctions and their
      structural proteins, the connexins. In this review, emerging roles of connexins
      and gap junctions in the process of tissue invasion are proposed. 

PMID- 24457199
TI  - Atrial fibrillation-associated connexin40 mutants make hemichannels and
      synergistically form gap junction channels with novel properties.
AB  - Mutations of Cx40 (GJA5) have been identified in people with lone chronic atrial
      fibrillation including G38D and M163V which were found in the same patient. We
      used dual whole cell patch clamp procedures to examine the transjunctional
      voltage (Vj) gating and channel conductance properties of these two rare mutants.
      Each mutant exhibited slight alterations of Vj gating properties and increased
      the gap junction channel conductance (gammaj) by 20-30 pS. While co-expression of
      the two mutations had similar effects on Vj gating, it synergistically increased
      gammaj by 50%. Unlike WTCx40 or M163V, G38D induced activity of a dominant 271 pS
      hemichannel.

PMID- 24457200
TI  - Connexins in lymphatic vessel physiology and disease.
AB  - Connexins are transmembrane proteins that form gap junction- and hemi-channels.
      Once inserted into the membrane, hemi-channels (connexons) allow for diffusion of
      ions and small molecules (<1 kDa) between the extracellular space and the
      cytosol. Gap junction channels allow diffusion of similar molecules between the
      cytoplasms of adjacent cells. The expression and function of connexins in blood
      vessels has been intensely studied in the last few decades. In contrast, only a
      few studies paid attention to lymphatic vessels; convincing in vivo data with
      respect to expression patterns of lymphatic connexins and their functional roles
      have only recently begun to emerge. Interestingly, mutations in connexin genes
      have been linked to diseases of lymphatic vasculature, most notably primary and
      secondary lymphedema. This review summarizes the available data regarding
      lymphatic connexins. More specifically it addresses (i) early studies aimed at
      presence of gap junction-like structures in lymphatic vessels, (ii) more recent
      studies focusing on lymphatic connexins using genetically engineered mice, and
      (iii) results of clinical studies that have reported lymphedema-linked mutations
      in connexin genes.

PMID- 24457201
TI  - Ribosomal protein S3 interacts with the NF-kappaB inhibitor IkappaBalpha.
AB  - Ribosomal protein S3 (RPS3) is part of nuclear, transcriptionally active and
      cytoplasmic inhibitory complexes containing NF-kappaB variant p65. We show that
      in resting HEK293 cells, RPS3 interacts with NF-kappaB inhibitor IkappaBalpha. In
      contrast, efficient co-precipitation of p65 with RPS3 was only achieved in the
      presence of ectopic IkappaBalpha. In addition, a strong in vitro interaction was
      observed between RPS3 and IkappaBalpha, while binding between RPS3 and p65 was
      very weak. Furthermore, IkappaBalpha facilitated the reconstitution of p65 and
      RPS3 into one complex in vitro. Our results suggest that IkappaBalpha sequesters
      not only p65 but also RPS3 in the cytoplasm. This would ensure maintenance of an
      RPS3 pool for the NF-kappaB pathway as well as equimolar release of RPS3 and p65
      upon stimulation. 

PMID- 24457203
TI  - A polysomnographic and clinical study of sleep disorders in patients with Behcet
      and neuro-Behcet syndrome.
AB  - Brainstem is the most common site of involvement in neuro-Behcet syndrome (NBS).
      On the other hand, the critical importance of this anatomical region in the
      regulation of sleep has been disregarded in the literature. We aimed to
      investigate the microstructure of sleep in patients with Behcet syndrome (BS) and
      NBS. Patients were allocated to 2 groups: (1) BS without any neurological
      involvement and (2) NBS with brainstem lesions only. A control group was also
      enrolled in this study. The comparison of polysomnographic parameters between all
      patients (BS and NBS) with the control group showed that sleep onset was longer
      (p = 0.006), the duration of superficial NREM sleep stage (N2) was significantly
      longer (p = 0.018), and the respiratory disturbance index was significantly
      higher (p = 0.034) in patients. Sleep apnea and restless legs syndrome are more
      commonly observed in BS and NBS. Our findings emphasize the importance of
      questioning the quality of sleep and its disorders in patients with BS in order
      to better handle the common somatic complaints in these patients, such as fatigue
      or daytime sleepiness

PMID- 24457202
TI  - Connexins: mechanisms regulating protein levels and intercellular communication.
AB  - Intercellular communication can occur through gap junction channels, which are
      comprised of connexin proteins. Therefore, levels of connexins can directly
      correlate with gap junctional intercellular communication. Because gap junctions
      have a critical role in maintaining cellular homeostasis, the regulation of
      connexin protein levels is important. In the connexin life cycle, connexin
      protein levels can be modified through differential gene transcription or altered
      through trafficking and degradation mechanisms. More recently, significant
      attention has been directed to the pathways that cells utilize to increase or
      decrease connexin levels and thus indirectly, gap junctional communication. Here,
      we review the studies revealing the mechanisms that affect connexin protein
      levels and gap junctional intercellular communication. 

PMID- 24457204
TI  - Avoiding surrogate measures and incorporating subjective experience into clinical
      research.

PMID- 24457206
TI  - Health response system for Syria: beyond official narrative.

PMID- 24457205
TI  - A gender-sensitised weight loss and healthy living programme for overweight and
      obese men delivered by Scottish Premier League football clubs (FFIT): a pragmatic
      randomised controlled trial.
AB  - BACKGROUND: The prevalence of male obesity is increasing but few men take part in
      weight loss programmes. We assessed the effect of a weight loss and healthy
      living programme on weight loss in football (soccer) fans. METHODS: We did a two
      group, pragmatic, randomised controlled trial of 747 male football fans aged 35
      65 years with a body-mass index (BMI) of 28 kg/m(2) or higher from 13 Scottish
      professional football clubs. Participants were randomly assigned with SAS
      (version 9.2, block size 2-9) in a 1:1 ratio, stratified by club, to a weight
      loss programme delivered by community coaching staff in 12 sessions held every
      week. The intervention group started a weight loss programme within 3 weeks, and
      the comparison group were put on a 12 month waiting list. All participants
      received a weight management booklet. Primary outcome was mean difference in
      weight loss between groups at 12 months, expressed as absolute weight and a
      percentage of their baseline weight. Primary outcome assessment was masked.
      Analyses were based on intention to treat. The trial is registered with Current
      Controlled Trials, number ISRCTN32677491. FINDINGS: 374 men were allocated to the
      intervention group and 374 to the comparison group. 333 (89%) of the intervention
      group and 355 (95%) of the comparison group completed 12 month assessments. At 12
      months the mean difference in weight loss between groups, adjusted for baseline
      weight and club, was 4.94 kg (95% CI 3.95-5.94) and percentage weight loss,
      similarly adjusted, was 4.36% (3.64-5.08), both in favour of the intervention
      (p<0.0001). Eight serious adverse events were reported, five in the intervention
      group (lost consciousness due to drugs for pre-existing angina, gallbladder
      removal, hospital admission with suspected heart attack, ruptured gut, and
      ruptured Achilles tendon) and three in the comparison group (transient ischaemic
      attack, and two deaths). Of these, two adverse events were reported as related to
      participation in the programme (gallbladder removal and ruptured Achilles
      tendon). INTERPRETATION: The FFIT programme can help a large proportion of men to
      lose a clinically important amount of weight; it offers one effective strategy to
      challenge male obesity. FUNDING: Scottish Government and The UK Football Pools
      funded delivery of the programme through a grant to the Scottish Premier League
      Trust. The National Institute for Health Research Public Health Research
      Programme funded the assessment (09/3010/06).

PMID- 24457207
TI  - Obesity in men: are professional football clubs onside?

PMID- 24457208
TI  - Telecytological diagnosis of space-occupying lesions of the liver.
AB  - OBJECTIVE: In this study, the efficiency of telemedical consulting with regard to
      fine needle aspirates from space-occupying lesions (SOLs) of the liver is
      investigated for the first time. STUDY DESIGN: The study includes fine needle
      aspirations from 62 patients, 33 with hepatocellular carcinoma (HCC) and 29 with
      non-hepatic tumors. Using the Internet-based iPath system, the initial
      pathologist submitted 1-8 images from smears and cell block sections. One
      consultant assessed the cytological and another one the histological images. Both
      made their diagnoses independent of each other. A final diagnosis was made by
      immunochemistry of cell block sections. The cytological images were analyzed
      retrospectively for the occurrence of the most typical HCC indicators. The number
      of these indicators was related to the initial diagnoses of the three
      pathologists, and possible reasons for diagnostic errors were analyzed based on
      this analysis. RESULTS: The accuracy of the preliminary telemedical diagnoses
      regarding HCC was 82.0% for the cytological images and 87.7% for the histological
      images. Most of the false diagnoses occurred in tumors with unusual cytological
      and histological patterns. CONCLUSIONS: Telemedical consulting is a valuable tool
      to obtain a second opinion. However, for improvement of the diagnosis of HCC,
      supplementary immunochemical tests are necessary.

PMID- 24457209
TI  - WITHDRAWN: Positive experience of family members in emergency departments: A
      commentary.
AB  - This article has been withdrawn at the request of 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- 24457210
TI  - Elevated osteoprotegerin predicts declining renal function in elderly women: a 10
      year prospective cohort study.
AB  - BACKGROUND: Elevated osteoprotegerin (OPG) levels are inversely correlated with
      creatinine clearance and end-stage renal disease in patients with diabetes,
      however its role in predicting decline in renal function and progression to a
      more advanced stage disease in the elderly general population is unknown.
      METHODS: This was a prospective cohort study of 1,157 elderly women with serum
      OPG measured in 1998 and renal function estimated using serum creatinine and
      cystatin C-based estimated glomerular filtration rate (eGFR) at 5-yearly
      intervals. The primary objective of the study was to determine the relationship
      of circulating OPG levels with 5- and 10-year renal decline. RESULTS: At
      baseline, participants with elevated OPG above the median (>=2.2 ng/ml) had a
      5.0% lower CKD-EPI-creatinine and cystatin C eGFR compared to participants with
      lower OPG levels. In multivariable-adjusted linear regression models, elevated
      OPG levels at baseline were associated with greater 5- and 10-year decline in CKD
      EPI-creatinine and cystatin C eGFR (-0.105, p = 0.002 and -0.104, p = 0.010,
      respectively). Elevated OPG at baseline was associated with increased 5- and 10
      year risk of rapid renal decline (OR 2.13, 95% CI 1.33-3.43, p = 0.002 and OR
      4.10, 95% CI 1.49-11.27, p = 0.006, respectively) and renal disease
      hospitalizations or deaths (HR 1.99, 95% CI 1.31-3.03, p = 0.001) after adjusting
      for known risk factors. CONCLUSION: Elevated OPG levels are associated with long
      term renal dysfunction and may be provide a useful biomarker to predict the
      trajectory of renal decline in older women.

PMID- 24457211
TI  - Modeling the dynamical effects of anesthesia on brain circuits.
AB  - General anesthesia is a neurophysiological state that consists of
      unconsciousness, amnesia, analgesia, and immobility along with maintenance of
      physiological stability. General anesthesia has been used in the United States
      for more than 167 years. Now, using systems neuroscience paradigms how
      anesthetics act in the brain and central nervous system to create the states of
      general anesthesia is being understood. Propofol is one of the most widely used
      and the most widely studied anesthetics. When administered for general anesthesia
      or sedation, the electroencephalogram (EEG) under propofol shows highly
      structured, rhythmic activity that is strongly associated with changes in the
      patient's level of arousal. These highly structured oscillations lend themselves
      readily to mathematical descriptions using dynamical systems models. We review
      recent model descriptions of the commonly observed EEG patterns associated with
      propofol: paradoxical excitation, strong frontal alpha oscillations,
      anteriorization and burst suppression. Our analysis suggests that propofol's
      actions at GABAergic networks in the cortex, thalamus and brainstem induce
      profound brain dynamics that are one of the likely mechanisms through which this
      anesthetic induces altered arousal states from sedation to unconsciousness.
      Because these dynamical effects are readily observed in the EEG, the mathematical
      descriptions of how propofol's EEG signatures relate to its mechanisms of action
      in neural circuits provide anesthesiologists with a neurophysiologically based
      approach to monitoring the brain states of patients receiving anesthesia care. 

PMID- 24457213
TI  - Grid-layout and theta-modulation of layer 2 pyramidal neurons in medial
      entorhinal cortex.
AB  - Little is known about how microcircuits are organized in layer 2 of the medial
      entorhinal cortex. We visualized principal cell microcircuits and determined
      cellular theta-rhythmicity in freely moving rats. Non-dentate-projecting,
      calbindin-positive pyramidal cells bundled dendrites together and formed patches
      arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum, and
      cholinergic inputs. Calbindin-negative, dentate-gyrus-projecting stellate cells
      were distributed across layer 2 but avoided centers of calbindin-positive
      patches. Cholinergic drive sustained theta-rhythmicity, which was twofold
      stronger in pyramidal than in stellate neurons. Theta-rhythmicity was cell-type
      specific but not distributed as expected from cell-intrinsic properties. Layer 2
      divides into a weakly theta-locked stellate cell lattice and spatiotemporally
      highly organized pyramidal grid. It needs to be assessed how these two distinct
      principal cell networks contribute to grid cell activity. 

PMID- 24457212
TI  - Origin and spread of de novo genes in Drosophila melanogaster populations.
AB  - Comparative genomic analyses have revealed that genes may arise from ancestrally
      nongenic sequence. However, the origin and spread of these de novo genes within
      populations remain obscure. We identified 142 segregating and 106 fixed testis
      expressed de novo genes in a population sample of Drosophila melanogaster. These
      genes appear to derive primarily from ancestral intergenic, unexpressed open
      reading frames, with natural selection playing a significant role in their
      spread. These results reveal a heretofore unappreciated dynamism of gene content.

PMID- 24457214
TI  - 1D-1D Coulomb drag signature of a Luttinger liquid.
AB  - One-dimensional (1D) interacting electronic systems exhibit distinct properties
      when compared to their counterparts in higher dimensions. We report Coulomb drag
      measurements between vertically integrated quantum wires separated by a barrier
      only 15 nanometers wide. The temperature dependence of the drag resistance is
      measured in the true 1D regime where both wires have less than one 1D subband
      occupied. As a function of temperature, an upturn in the drag resistance is
      observed below a temperature T* ~ 1.6 kelvin. This crossover in Coulomb drag
      behavior is consistent with Tomonaga-Luttinger liquid models for the 1D-1D drag
      between quantum wires.

PMID- 24457215
TI  - Island cells control temporal association memory.
AB  - Episodic memory requires associations of temporally discontiguous events. In the
      entorhinal-hippocampal network, temporal associations are driven by a direct
      pathway from layer III of the medial entorhinal cortex (MECIII) to the
      hippocampal CA1 region. However, the identification of neural circuits that
      regulate this association has remained unknown. In layer II of entorhinal cortex
      (ECII), we report clusters of excitatory neurons called island cells, which
      appear in a curvilinear matrix of bulblike structures, directly project to CA1,
      and activate interneurons that target the distal dendrites of CA1 pyramidal
      neurons. Island cells suppress the excitatory MECIII input through the feed
      forward inhibition to control the strength and duration of temporal association
      in trace fear memory. Together, the two EC inputs compose a control circuit for
      temporal association memory. 

PMID- 24457216
TI  - The New Madrid Seismic Zone: not dead yet.
AB  - The extent to which ongoing seismicity in intraplate regions represents long
      lived aftershock activity is unclear. We examined historical and instrumental
      seismicity in the New Madrid central U.S. region to determine whether present-day
      seismicity is composed predominantly of aftershocks of the 1811-1812 earthquake
      sequence. High aftershock productivity is required both to match the observation
      of multiple mainshocks and to explain the modern level of activity as
      aftershocks; synthetic sequences consistent with these observations substantially
      overpredict the number of events of magnitude >= 6 that were observed in the past
      200 years. Our results imply that ongoing background seismicity in the New Madrid
      region is driven by ongoing strain accrual processes and that, despite low
      deformation rates, seismic activity in the zone is not decaying with time. 

PMID- 24457217
TI  - Long-term practice induced plasticity in the primary motor cortex innervating the
      ankle flexor in football juggling experts.
AB  - The aim of this study was to investigate the plasticity of M1 innervating the
      tibialis anterior muscle (TA) induced by the long-term practice of football
      juggling using a transcranial magnetic stimulation (TMS) technique. Ten football
      juggling experts and ten novices participated in this study. Motor evoked
      potentials (MEP) and the H-reflex were recorded from the right TA during
      isometric dorsiflexion at 10% of maximum voluntary contraction. The MEP input
      output curve of the experts was steeper than that of the novices, and reduced
      short-interval intracortical inhibition and long-interval intracortical
      inhibition were observed in the experts. In contrast, the ratio of Hmax to Mmax
      did not differ between the groups. Our results show that football juggling
      experts displayed enhanced excitability in the M1 innervating the TA, which was
      induced by the long-term practice of the ankle movements required to perform
      football juggling well. 

PMID- 24457218
TI  - Relationship Violence, Fear, and Exposure to Youth Violence Among Adolescents in
      New York City.
AB  - Previous research has shown that there is an overlap between experiences of youth
      violence and adolescent relationship violence. Yet, little research exists which
      investigates the sex differences in the associations between specific types of
      youth violence and relationship violence while controlling for potential
      confounders. This study addresses this gap in the literature by exploring the
      associations between experiences of youth violence and receiving and delivering
      relationship violence in an urban adolescent sample. From 2006 to 2007, 1,454
      adolescents aged 13 to 21 years in New York City completed an anonymous survey
      that included the validated Conflict in Adolescent Relationships Inventory that
      estimates experiences of relationship violence in the previous year as well as
      the prevalence of various exposures to youth violence. Bivariate and multivariate
      analyses assessed the overlap between experiencing other types of youth violence
      and delivering and receiving physical relationship violence and sexual coercion.
      Compared with youth in nonviolent relationships, we found a significant
      association between delivering and receiving relationship physical violence and
      sexual coercion with participating in a fight, missing school due to fear, being
      threatened/injured with a weapon, gang membership, and carrying a weapon among
      both males and females. We also identified the sex differences between these
      specific associations of youth and relationship violence. Service providers
      working with adolescents experiencing relationship violence should be aware that
      they face a higher concurrent risk of experiencing or participating in other
      forms of youth violence. Likewise, providers working in the area of youth
      violence intervention and prevention should consider the possibility of
      concurrent relationship violence. Based on these findings, further research
      should explore whether interventions targeting relationship violence can also
      impact participation in youth violence and vice versa.

PMID- 24457219
TI  - Effective Advocacy in Rural Domains: Applying an Ecological Model to
      Understanding Advocates' Relationships.
AB  - Past scholarship has explored the ecological model as it pertains to intimate
      partner violence from the victim's perspective. Missing from this literature is
      the application of the ecological model to victim advocates, specifically rural
      victim advocates. This article explores the microsystem and exosystem levels of
      the ecological model to understand victim advocates' relationships with their
      clients and criminal justice personnel. To investigate these relationships, we
      used a sample of rural advocates located within the Mississippi Delta Region. The
      findings from the interviews and focus group indicate that the density of rural
      relationships both help facilitate and create barriers to effective victim
      advocacy. Social capital specific to the rural domain is being generated by the
      advocates to benefit themselves and their clients.

PMID- 24457220
TI  - The Impact of Sexual Abuse Committed by a Child on Mental Health in Adulthood.
AB  - Numerous research studies document the negative mental health outcomes associated
      with the experience of childhood sexual abuse. In addition, factors such as one's
      relationship with the perpetrator and the severity of the abuse predict the
      likelihood of future mental health problems. Less attention, however, has focused
      on the age of the perpetrator, and recent years have seen an increased interest
      in children who display sexual behavior problems. College students completed
      measures of mental health functioning and retrospective reports of maltreatment
      histories. Participants were categorized as abused by an adult (n = 48), teenager
      (n = 39), or another child (n = 37), and non-abused (n = 219). Victims of abuse,
      regardless of perpetrator age, displayed higher levels of mental health problems
      than non-abused participants. There were no differences between the abused groups
      on any of the mental health outcomes; however, individuals who were abused by
      other children were less likely to label their experiences as abuse.

PMID- 24457221
TI  - "I Wish the Hitting Would Stop . . . " An Assessment of a Domestic Violence
      Education Program for Elementary Students.
AB  - School officials across the country have recognized that many of their students
      live in homes where domestic violence occurs. As a result, several elementary
      schools have implemented education-based programs focused on this issue. The
      current study evaluates the efficacy of the "I Wish the Hitting Would Stop . . .
      " program that was presented to elementary school children in two school
      districts in the Midwest. This study examines the level of knowledge retention by
      students who participated in the "I Wish the Hitting Would Stop . . . " program
      during the 2010-2011 and 2011-2012 academic years. Fourth- and fifth-grade
      students responded to open-ended questions regarding their understanding of
      domestic violence and their retention of the concepts presented in the "I Wish
      the Hitting Would Stop . . . " curriculum. While the results suggest that
      students retain the information presented in the program, there also appears to
      be a gender difference in knowledge retention.

PMID- 24457222
TI  - Structural abnormalities in schizophrenia: further evidence on the key role of
      the anterior cingulate cortex.
AB  - OBJECTIVE: The present study examined whole-brain structural abnormalities in
      schizophrenia, with a special focus on the anterior and posterior cingulate
      cortex (ACC, PCC) as this is an understudied issue in schizophrenia. METHOD:
      Whole-brain voxel-based morphometry analyses of gray matter (GM) and white matter
      (WM) were performed to detect volumetric differences between 14 patients with
      schizophrenia and 14 healthy controls matched for age, sex, educational level and
      parents' educational level. We examined within-group GM and WM correlations and
      completed the analysis with measurements of sulci in medial cortical areas.
      RESULTS: Compared with the healthy controls, the schizophrenic patients showed
      significant decreases in GM volumes in the ACC and PCC, and in neighboring WM
      regions such as the corpus callosum and the fimbriae of the fornix. Moreover, the
      patient group also displayed a negative correlation between volumes of GM and WM
      in the ACC. Finally, the patients showed significantly reduced volumes in the
      right cingulate sulci and left inferior frontal sulci. CONCLUSION: Our results
      replicate typical brain-structural abnormalities with new findings in the medial
      prefrontal cortex, suggested to be a key region in this disorder.

PMID- 24457223
TI  - In situ gelation of PEG-PLGA-PEG hydrogels containing high loading of
      hydroxyapatite: in vitro and in vivo characteristics.
AB  - Thermosensitive hydrogels are renowned carriers that are used to deliver a
      variety of drugs with the aim of combating diseases. In this study, the
      injectability of thermosensitive hydrogels comprised of poly(ethylene glycol)
      poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG, PELGE)
      and hydroxyapatite (HA) were examined for their ability to deliver bone
      morphological protein 2 (BMP-2). The physicochemical characteristics of PELGE,
      HA, and PELGE/HA hydrogel composites were investigated by (1)H NMR, GPC, FTIR,
      XRD, SEM, and TEM. The rheological properties, injectability, in vitro
      degradation, and in vivo biocompatibility were investigated. The hydrogel with a
      weight ratio of 4:6 of polymer to HA was found to be resistant to auto-catalyzed
      degradation of acidic monomers (LA, GA) for a period of 70 days owing to the
      presence of alkaline HA. Injectability was quantitatively determined by the
      ejected weight of the hydrogel composite at room temperature and was a close
      match to the weight amount predetermined by the syringe pump. The results not
      only revealed that the PELGE/HA hydrogel composite presented a minor tissue
      response in the subcutis of ICR mice at eight weeks, but they also indicated an
      acceptable tolerance of the hydrogel composite in animals. Thus, PELGE/HA
      hydrogel composite is expected to be a promising injectable orthopedic substitute
      because of its desirable thermosensitivity and injectability.

PMID- 24457224
TI  - Impact of the change in urinary and sexual function on health-related quality of
      life after once daily low-dose mirodenafil treatment in patients with organic
      erectile dysfunction.
AB  - OBJECTIVE: We aimed to evaluate whether changes in urinary and sexual function
      can influence health-related quality of life. PATIENTS AND METHODS: Out of 54
      recruited patients, 36 were enrolled, and data for 30 participants with erectile
      dysfunction were available. At baseline and after 1 and 2 months, each
      participant completed the International Index of Erectile Function (IIEF-15), the
      International Prostate Symptom Score (IPSS) and the Medical Outcomes Study Short
      Form 36-Item Health Survey (SF-36). Uroflowmetry, post-voiding residual volume
      and the nocturnal penile tumescence (NPT) test were performed at baseline and at
      the study's conclusion. RESULTS: Compared with baseline, the IPSS, IIEF-15, peak
      urinary flow rate, NPT parameters and mental component of the SF-36 exhibited
      significant improvement at the study's conclusion. Among the symptomatic
      parameters, the changes in the storage and erectile function parameters
      contributed significantly to the change in the mental component score on the SF
      36 (p = 0.007, R(2) = 0.502). CONCLUSIONS: The daily administration of low-dose
      mirodenafil (50 mg) produced improvements in urinary and erectile function with
      or without sexual stimulation. Furthermore, this therapy enhanced the mental
      component of health-related quality of life by improving storage and erectile
      symptoms.

PMID- 24457226
TI  - Access, continuity of care and consultation quality: which best predicts urgent
      cancer referrals from general practice?
AB  - BACKGROUND: For some cancers, late presentation is associated with poor survival.
      In England, less than half of patients are diagnosed following a general
      practitioner-initiated urgent referral. We explore whether particular practice or
      practitioner characteristics are associated with use of the urgent referral
      system. METHODS: The study sample was 603/614 practices in the East Midlands.
      Logistic regression models were fitted to investigate relationships between
      cancer detection rate, how easy it is to book appointments quickly, in advance or
      with a preferred doctor, and whether patients have confidence and trust in the
      doctor. RESULTS: The percentage of patients who definitely have confidence and
      trust in the doctor was positively associated with the cancer detection rate
      [odds ratio = 1.08 (95% confidence interval (CI) 1.01, 1.15) per 10 percentage
      points]. When all four survey variables were modelled together, the percentage of
      patients who were able to see a preferred doctor was negatively associated with
      the cancer detection rate [odds ratio = 0.93 (95% CI 0.88, 0.98) per 10
      percentage points]. CONCLUSIONS: Our analyses suggest that in the UK National
      Health Service, confidence and trust in the doctor may be more important in
      cancer detection than the ease of access or whether there is choice of doctor.

PMID- 24457225
TI  - Aplysia Ganglia preparation for electrophysiological and molecular analyses of
      single neurons.
AB  - A major challenge in neurobiology is to understand the molecular underpinnings of
      neural circuitry that govern a specific behavior. Once the specific molecular
      mechanisms are identified, new therapeutic strategies can be developed to treat
      abnormalities in specific behaviors caused by degenerative diseases or aging of
      the nervous system. The marine snail Aplysia californica is well suited for the
      investigations of cellular and molecular basis of behavior because neural
      circuitry underlying a specific behavior could be easily determined and the
      individual components of the circuitry could be easily manipulated. These
      advantages of Aplysia have led to several fundamental discoveries of neurobiology
      of learning and memory. Here we describe a preparation of the Aplysia nervous
      system for the electrophysiological and molecular analyses of individual neurons.
      Briefly, ganglion dissected from the nervous system is exposed to protease to
      remove the ganglion sheath such that neurons are exposed but retain neuronal
      activity as in the intact animal. This preparation is used to carry out
      electrophysiological measurements of single or multiple neurons. Importantly,
      following the recording using a simple methodology, the neurons could be isolated
      directly from the ganglia for gene expression analysis. These protocols were used
      to carry out simultaneous electrophysiological recordings from L7 and R15
      neurons, study their response to acetylcholine and quantitating expression of
      CREB1 gene in isolated single L7, L11, R15, and R2 neurons of Aplysia. 

PMID- 24457227
TI  - Usability testing of a computerized communication tool in a diverse urban
      pediatric population.
AB  - BACKGROUND: Developed in Norway, Sisom is an interactive, rigorously tested,
      computerized, communication tool designed to help children with cancer express
      their perceived symptoms/problems. Children travel virtually from island to
      island rating their symptoms/problems. While Sisom has been found to
      significantly improve communication in patient consultations in Norway, usability
      testing is warranted with US children prior to further use in research studies.
      OBJECTIVE: The objective of this study was to determine the usability of Sisom in
      a sample of English- and Spanish-speaking children in an urban US community.
      METHODS: A mixed-methods usability study was conducted with a purposive sample of
      healthy children and children with cancer. Semistructured interviews were used to
      assess healthy children's symptom recognition. Children with cancer completed 8
      usability tasks captured with Morae 3.3 software. Data were downloaded,
      transcribed, and analyzed descriptively. RESULTS: Four healthy children and 8
      children with cancer participated. Of the 44 symptoms assessed, healthy children
      recognized 15 (34%) pictorial symptoms immediately or indicated 13 (30%) pictures
      were good representations of the symptom. Six children with cancer completed all
      tasks. All children navigated successfully from one island to the next, ranking
      their symptom/problem severity, clicking the magnifying glass for help, or asking
      the researcher for assistance. All children were satisfied with the aesthetics
      and expressed an interest in using Sisom to communicate their symptoms/problems.
      CONCLUSIONS: A few minor suggestions for improvement and adjustment may optimize
      the use of Sisom for US children. IMPLICATIONS FOR PRACTICE: Sisom may help
      clinicians overcome challenges assessing children's complex symptoms/problems in
      a child-friendly manner.

PMID- 24457228
TI  - Women with breast cancer: experience of chemotherapy-induced pain: triangulation
      of methods.
AB  - BACKGROUND: Chemotherapy treatment for cancer diseases can cause body pain during
      adjuvant therapy. OBJECTIVE: The aim was to describe the perceived impact of
      adjuvant chemotherapy-induced pain (CHIP) on the daily lives of women with newly
      diagnosed breast cancer, using triangulation. METHOD: Fifty-seven women scheduled
      for chemotherapy in doses of 75 mg/m or greater of epirubicin and/or docetaxel
      participated. Twenty-two of these women registered pain with values of 4 or more
      on the visual analog scale on day 10 following chemotherapy. Of these 22, 16
      participated in an interview and colored a printed body image. A qualitative
      thematic stepwise analysis of the interviews was performed. RESULTS: Chemotherapy
      induced pain had a profound impact on daily life. Ten women reported the worst
      possible pain, with visual analog scale scores of 8 to 10. Three different
      categories crystallized: perception (A) of manageable pain, which allowed the
      women to maintain their daily lives; perception (B) of pain beyond imagination,
      whereby the impact of pain had become more complex; and perception (C) of
      crippling pain, challenging the women's confidence in survival. CONCLUSIONS: The
      findings highlight the inability to capture CHIP with 1 method only; it is thus
      necessary to use complimentary methods to capture pain. We found that pain had a
      considerable impact on daily life, with surprisingly high scores of perceived
      pain, findings that to date have been poorly investigated qualitatively.
      IMPLICATIONS FOR PRACTICE: Nurses need to (1) better identify, understand and
      treat CHIP, using instruments and protocols; and (2) provide improved
      communication about pain and pain management.

PMID- 24457229
TI  - Insulin-like growth factor-II mRNA-binding protein 3 expression in effusion
      cytology: a marker for metastatic adenocarcinoma cells and a potential prognostic
      indicator in gastric adenocarcinoma.
AB  - OBJECTIVE: The aim of our study was to identify the diagnostic value of insulin
      like growth factor-II mRNA-binding protein 3 (IMP3) in distinguishing metastatic
      adenocarcinoma cells (MAC) from reactive mesothelial cells (RMC) in effusions. We
      also investigated the role of IMP3 as a prognostic indicator for patients with
      malignant effusion. STUDY DESIGN: A total of 156 cell block specimens, including
      116 malignant effusions with MAC and 40 benign effusions with RMC, were subjected
      to immunocytochemical staining for IMP3. RESULTS: Immunocytochemical studies
      showed positive staining for IMP3 in 91 of 116 (78.4%) cases of MAC and in 3 of
      40 (7.5%) cases of RMC. With regard to distinguishing MAC from RMC, the IMP3
      reactivity was found to be 78.4% sensitive and 92.5% specific with a positive
      predictive value of 96.8% and a negative predictive value of 59.7%. Diffuse IMP3
      expression (>25%) in MAC from patients with gastric adenocarcinoma was associated
      with shorter survival (p = 0.001). CONCLUSION: Our data suggest that IMP3 is a
      helpful marker for differentiating MAC from RMC, and that diffuse IMP3 expression
      is a poor prognostic indicator in patients with gastric adenocarcinoma and
      malignant effusion.

PMID- 24457230
TI  - Trifunctional Ir(III) ppy-type asymmetric phosphorescent emitters with ambipolar
      features for highly efficient electroluminescent devices.
AB  - Simple trifunctional Ir(III) ppy-type asymmetric phosphorescent emitters with
      ambipolar character are reported, which afford highly efficient OLEDs. 

PMID- 24457232
TI  - Thymomas: the need for prospective studies.

PMID- 24457233
TI  - Screening high-risk populations for lung cancer: guideline recommendations.
AB  - INTRODUCTION: The aim of this practice guideline was to develop evidence-based
      recommendations for screening high-risk populations for lung cancer. METHODS: The
      guideline was developed using the methods of Cancer Care Ontario's Program in
      Evidence-Based Care. The core methodology of the Program in Evidence-Based Care's
      guideline development process is systematic review. A systematic review had
      recently been completed by a collaboration of the American Cancer Society, the
      American College of Chest Physicians, the American Society of Clinical Oncology,
      and the National Comprehensive Cancer Network. The evidence from that systematic
      review formed the basis of the recommendations, which were reviewed, and amended
      where necessary, by clinical experts in the fields of medical and radiation
      oncology, radiology, lung disease, and population health. RESULTS: The systematic
      review included eight randomized controlled trials and 13 single-arm studies
      evaluating screening with low-dose computed tomography (LDCT) in patients at risk
      for lung cancer. One large randomized trial reported a statistically significant
      reduction in lung cancer mortality with LDCT at 6 years compared with chest
      radiography. The practice guideline recommendations generally align with the
      parameters of the National Lung Screening Study. Deviations were described and
      justified by the guideline working group. The recommendations support screening
      persons at high-risk for lung cancer with advice for determining a positive
      result on LDCT, appropriate follow-up, and optimal screening interval.
      CONCLUSION: The benefits of screening high-risk populations for lung cancer with
      LDCT outweigh the harms if screening is implemented in a strictly controlled
      manner.

PMID- 24457234
TI  - Nationwide quality improvement in lung cancer care: the role of the Danish Lung
      Cancer Group and Registry.
AB  - INTRODUCTION: To improve prognosis and quality of lung cancer care the Danish
      Lung Cancer Group has developed a strategy consisting of national clinical
      guidelines and a clinical quality and research database. The first edition of our
      guidelines was published in 1998 and our national lung cancer registry was opened
      for registrations in 2000. This article describes methods and results obtained by
      multidisciplinary collaboration and illustrates how quality of lung cancer care
      can be improved by establishing and monitoring result and process indicators.
      METHODS: A wide range of indicators was established, validated, and monitored. By
      registration of all lung cancer patients since the year 2000, data on more than
      40,000 patients have been included in the database. Results are reported
      periodically/quarterly and submitted to formal auditing on an annual basis.
      RESULTS: Improvements in all outcome indicators are documented and statistically
      significant. Thus the 1-year overall survival rate has increased between 2003 and
      2011 from 36.6% to 42.7%, the 2-year survival rate from 19.8% to 24.3%, and the 5
      year survival rate from 9.8% to 12.1%. Five-year survival after surgical
      resection has increased from 39.5% to 48.1%. Improvements of waiting times,
      accordance between cTNM and pTNM, and resection rates are documented. CONCLUSION:
      The Danish experience shows that a national quality management system including
      national guidelines, a database with high data quality, frequent reports, audit
      and commitment from all stakeholders can contribute to improve clinical practice,
      improve core results, and reduce regional differences.

PMID- 24457235
TI  - Stage-adjusted lung cancer survival does not differ between low-income Blacks and
      Whites.
AB  - INTRODUCTION: Few lung cancer studies have focused on lung cancer survival in
      underserved populations. We conducted a prospective cohort study among 81,697
      racially diverse and medically underserved adults enrolled in the Southern
      Community Cohort Study throughout an 11-state area of the Southeast from March
      2002 to September 2009. METHODS: Using linkages with state cancer registries, we
      identified 501 incident non-small-cell lung cancer cases. We applied Cox
      proportional hazards models to estimate hazard ratios (HRs) and 95% confidence
      intervals (CIs) for subsequent mortality among black and white participants.
      RESULTS: The mean observed follow-up time (the time from diagnosis to death or
      end of follow-up) was 1.25 years (range, 0-8.3 years) and 75% (n = 376) of cases
      died during follow-up. More blacks were diagnosed at distant stage than whites
      (57 versus 45%; p = 0.03). In multivariable analyses adjusted for pack-years of
      smoking, age, body mass index, health insurance, socioeconomic status and disease
      stage, the lung cancer mortality HR was higher for men versus women (HR = 1.41;
      95% CI, 1.09-1.81) but similar for blacks versus whites (HR = 0.99; 95% CI, 0.74
      1.32). CONCLUSION: These findings suggest that although proportionally more
      blacks present with distant-stage disease there is no difference in stage
      adjusted lung cancer mortality between blacks and whites of similar low
      socioeconomic status.

PMID- 24457236
TI  - Associations between TS, TTF-1, FR-alpha, FPGS, and overall survival in patients
      with advanced non-small-cell lung cancer receiving pemetrexed plus carboplatin or
      gemcitabine plus carboplatin as first-line chemotherapy.
AB  - INTRODUCTION: Pemetrexed is effective in the treatment of non-small-cell lung
      cancer, mainly in nonsquamous cell carcinomas. Inhibition of thymidylate synthase
      (TS) is considered the key mechanism of action. Folate receptor-alpha facilitates
      uptake of pemetrexed. Polyglutamation by folylpolyglutamate synthetase enhances
      activity and prolongs cellular retention of pemetrexed. Thyroid transcription
      factor-1 (TTF-1) is mainly positive in nonsquamous cell carcinoma and has been
      proposed as a marker for sensitivity to pemetrexed. The aim was to investigate
      associations between these biomarkers and survival in patients who participated
      in a phase III trial comparing pemetrexed plus carboplatin with gemcitabine plus
      carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer (n
      = 436). In this study, there was no difference in overall survival between the
      two regimens. METHODS: Formalin-fixed, paraffin-embedded biopsies were collected.
      Percentages of tumor cells positive and highly positive for the biomarkers were
      assessed using immunohistochemistry (IHC) and an IHC score was calculated (range,
      0-200). RESULTS: Two hundred thirty-six biopsies were analyzed (pemetrexed plus
      carboplatin: n = 114, gemcitabine plus carboplatin: n = 122). There was a
      significant difference in overall survival between those with TTF-1-positive and 
      negative tumors (10.4 versus 6.0 months; p < 0.001) and those with a low and a
      high TS IHC score (9.7 versus 6.2 months; p < 0.001). Folate receptor-alpha and
      folylpolyglutamate synthetase were not significant prognostic factors. In
      multivariate analyses adjusting for established prognostic characteristics, TS (p
      = 0.002) and TTF-1 (p = 0.003) remained significant. There were no differences in
      survival between the treatment arms depending on biomarker scores. CONCLUSIONS:
      TTF-1 positivity and low TS level were associated with prolonged survival. The
      associations between the biomarkers and overall survival were similar for both
      chemotherapy regimens.

PMID- 24457237
TI  - Small-cell carcinoma in the setting of pulmonary adenocarcinoma: new insights in
      the era of molecular pathology.
AB  - INTRODUCTION: Transformation into small-cell lung carcinoma (SCLC) has been
      reported as an evolution of lung adenocarcinoma acquiring resistance to epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). However,
      spontaneous association of SCLC and adenocarcinoma also exists. We sought to
      compare patients' clinical features and mutation status of EGFR in each tumor
      component in these conditions. METHODS: Our study is based on nine consecutive
      cases of SCLC, occurring synchronously or after a previous diagnosis of pulmonary
      adenocarcinoma, with or without TKI-based therapy, diagnosed in Marie Lannelongue
      Surgical Center, France, between 2001 and 2013. Molecular analysis by DNA direct
      sequencing was performed to detect EGFR mutations on formalin-fixated tissue
      mostly from surgically resected tumors. RESULTS: Six patients had a metachronous
      occurrence of SCLC after adenocarcinoma (2 after TKI); three had a synchronous
      form. There were four combined SCLCs/adenocarcinomas. Seven adenocarcinoma
      components were EGFR mutated: five exon 19 deletions and two mutations in exon 21
      (L833_V834delinsFL and L858R). Four SCLC components were EGFR mutated. Two cases
      occurred in never-smoker women with adenocarcinoma treated with TKI: one with
      E872 mutation in exon 21 and one combined SCLC/adenocarcinoma with exon 19
      deletion in both components. Two cases were spontaneous: a SCLC with exon 19
      deletion occurring after a nonmutated adenocarcinoma and a combined
      SCLC/adenocarcinoma with exon 21 mutation (L833_V834delinsFL) in both components.
      CONCLUSION: SCLC developing in association with adenocarcinoma, either
      synchronously or metachronously, seem linked to EGFR mutation, regardless of TKI
      use. Our findings suggest that such associated cases should be tested for EGFR
      mutations.

PMID- 24457238
TI  - Effects of chemotherapy on survival of elderly patients with small-cell lung
      cancer: analysis of the SEER-medicare database.
AB  - INTRODUCTION: This retrospective cohort study was designed to analyze factors
      associated with administration of chemotherapy and to examine the impact of
      chemotherapy on survival among elderly patients with small-cell lung cancer
      (SCLC) in the community. METHODS: Elderly patients aged 65 years and older with
      SCLC diagnosed between 1992 and 2001 were selected from the Surveillance,
      Epidemiology, and End Results-Medicare database. Logistic regression was used to
      evaluate which covariates influenced receipt of chemotherapy. Cox proportional
      hazards regression was used to examine the influence of clinical and demographic
      variables on survival. The independent effect of chemotherapy on survival was
      determined using propensity scores and quantile regression. RESULTS: In the final
      cohort of 10,428 patients, 67.1% received chemotherapy, 39.1% received radiation,
      3.4% received surgery, and 21.8% received no treatment. The most common
      chemotherapy regimens included etoposide combined with either cisplatin or
      carboplatin. Patients aged 85 years and older were significantly less likely to
      receive chemotherapy compared with patients aged 65 to 69 years (odds ratio 0.17;
      95% confidence interval 0.14-0.21). Median survival for all patients was 7
      months. Factors associated with improved survival were being female, black race,
      having limited-stage disease, receiving any treatment, and having a lower
      comorbidity score. Quantile regression demonstrated that chemotherapy provided a
      6.5-month improvement in median survival (95% confidence interval 6.3-6.6;
      p<0.001). CONCLUSIONS: Statistically significant differences in the receipt of
      chemotherapy exist among elderly patients with SCLC. Chemotherapy is associated
      with a greater than 6-month improvement in median survival among elderly patients
      with SCLC, even in patients over the age of 80 years.

PMID- 24457239
TI  - Outcome and prognostic factors in bronchial carcinoids: a single-center
      experience.
AB  - INTRODUCTION: The aim of this study is to assess factors influencing survival in
      patients with bronchial carcinoids (BCs). METHODS: A retrospective review of our
      surgical database of patients operated for primary lung cancer with a final
      histologic diagnosis of BC in the period from January 1, 1995 to December 31,
      2010 was carried out. RESULTS: There were 126 patients (74 women): 83 had a
      typical carcinoid and 43 an atypical one (AC). All patients received a radical
      resection; systematic lymphadenectomy was accomplished in 120. Lymph nodal
      metastases were observed in 26 cases (12 N2) and were more frequent in ACs (p =
      0.009). Twelve patients received adjuvant therapy (chemo/radio/biological).
      Distant metastases (DM) and local tumor recurrence occurred in 28 (22%) and 8
      (6.3%) cases, respectively: DM were more frequent in ACs (p = 0.0001) and in N2
      patients (p = 0.0001). Smoke, atypical histology, lymph nodal metastases, and
      high cellular proliferative index demonstrated to be statistically negative
      prognostic factors. CONCLUSION: Even if characterized by an indolent behavior,
      BCs may spread to lymph node or distant or present with local recurrence. Amid
      all prognostic factors, the presence of DM demonstrated to be the strongest
      negative one.

PMID- 24457240
TI  - Identification of early t1b lung adenocarcinoma based on thin-section computed
      tomography findings.
AB  - INTRODUCTION: The aim of this study was to radiologically identify early lung
      adenocarcinoma in clinical T1bN0M0 lung cancer, based on pathological findings
      and long-term prognosis. METHODS: In this study, we reviewed lung nodules
      findings on thin-section computed tomography in 173 patients with clinical
      T1bN0M0 lung adenocarcinoma who underwent surgery between 2003 and 2007. The
      ratio of the size of solid attenuation to the maximum tumor dimension
      (consolidation/tumor [C/T] ratio) was calculated. We defined two groups of
      patients by C/T ratio cutoff levels of 0.00, 0.25, 0.50, 0.75, and 1.00 and
      compared the rates of pathological nonaggressive lung adenocarcinoma, overall
      survival, and recurrence rates between the groups. The percentages of predominant
      histological subtypes were compared between two groups divided by the optimal
      cutoff level. Various clinical factors were analyzed by univariate and
      multivariate analyses to predict pathological lymph node involvement. RESULTS:
      The median follow-up period was 62 months. All patients with C/T ratios of 0.5 or
      less were diagnosed as having pathological nonaggressive adenocarcinomas, and
      there was no recurrence; their 5-year overall survival rate was 97.4%, which was
      significantly better than that for patients with C/T ratios of greater than 0.5
      (76.2%). None of the ground-glass opacity-predominant tumors were predominantly
      solid adenocarcinoma with mucin. The C/T ratio of 0.5 or more was an independent
      predictor of lymph node involvement. CONCLUSION: In patients with clinical
      T1bN0M0 disease, the C/T ratio of 0.5 or less identified early lung
      adenocarcinoma. In patients with the identified early disease, a feasibility
      study of limited surgery may be warranted.

PMID- 24457241
TI  - Cost effectiveness of modified fractionation radiotherapy versus conventional
      radiotherapy for unresected non-small-cell lung cancer patients.
AB  - INTRODUCTION: Modified fractionation radiotherapy (RT), delivering multiple
      fractions per day or shortening the overall treatment time, improves overall
      survival for non -small-cell lung cancer (NSCLC) patients compared with
      conventional fractionation RT (CRT). However, its cost effectiveness is unknown.
      Therefore, we aimed to examine and compare the cost effectiveness of different
      modified RT schemes and CRT in the curative treatment of unresected NSCLC
      patients. METHODS: A probabilistic Markov model was developed based on individual
      patient data from the meta-analysis of radiotherapy in lung cancer (N = 2000).
      Dutch health care costs, quality-adjusted life years (QALYs), and net monetary
      benefits (NMBs) were compared between two accelerated schemes (very accelerated
      RT [VART] and moderately accelerated RT [MART]), two hyperfractionated schemes
      (using an identical (HRT) or higher (HRT) total treatment dose than CRT) and CRT.
      RESULTS: All modified fractionations were more effective and costlier than CRT
      (1.12 QALYs, &OV0556;24,360). VART and MART were most effective (1.30 and 1.32
      QALYs) and cost &OV0556;25,746 and &OV0556;26,208, respectively. HRT and HRT
      yielded less QALYs than the accelerated schemes (1.27 and 1.14 QALYs), and cost
      &OV0556;26,199 and &OV0556;29,683, respectively. MART had the highest NMB
      (&OV0556;79,322; 95% confidence interval [CI], &OV0556;35,478-&OV0556;133,648)
      and was the most cost-effective treatment followed by VART (&OV0556;78,347; 95%
      CI, &OV0556;64,635-&OV0556;92,526). CRT had an NMB of &OV0556;65,125 (95% CI,
      &OV0556;54,663-&OV0556;75,537). MART had the highest probability of being cost
      effective (43%), followed by VART (31%), HRT (24%), HRT (2%), and CRT (0%).
      CONCLUSION: Implementing accelerated RT is almost certainly more efficient than
      current practice CRT and should be recommended as standard RT for the curative
      treatment of unresected NSCLC patients not receiving concurrent chemo
      radiotherapy.

PMID- 24457242
TI  - ZIC1 is silenced and has tumor suppressor function in malignant pleural
      mesothelioma.
AB  - INTRODUCTION: Epigenetic inactivation of tumor suppressor genes is involved in
      the development of malignant pleural mesothelioma (MPM). ZIC1, a potential tumor
      suppressor gene involved in regulating cell growth and apoptosis, was
      investigated in MPM cell lines and tumors. METHODS: ZIC1 expression and promoter
      methylation were evaluated in MPM cell lines and tumor samples by quantitative
      polymerase chain reaction (PCR), Combined Bisulfite Restriction Analysis, and
      methylation-specific PCR. ZIC1 was reexpressed in cell lines and functional
      effects were assessed. miRNA expression was quantified by microarray and reverse
      transcription quantitative PCR. ZIC1 knockdown and miRNA inhibitors were used to
      study the relationship between ZIC1 and miRNA expression and confirmed by
      chromatin immunoprecipitation PCR. RESULTS: ZIC1 expression was low in MPM cells,
      and was correlated with ZIC1 promoter methylation and reversed upon decitabine
      treatment. ZIC1 reexpression inhibited proliferation and invasion in MPM cells
      whereas knockdown enhanced the growth of MeT-5A. In MPM tumor samples ZIC1
      expression was either low or undetectable, with promoter methylation observed in
      16 of 24 cases. The overexpression of miR-23a and miR-27a was reduced by ZIC1
      reexpression, with inhibitors of miR-23a or miR-27a reducing colony formation.
      miR-23a overexpression was also associated with shorter survival of MPM patients.
      CONCLUSION: ZIC1 is down-regulated in MPM through promoter methylation and acts
      as a tumor suppressor through down-regulation of its direct targets miR-23a and
      miR-27a.

PMID- 24457243
TI  - Outcome of multimodality treatment for 188 cases of type B3 thymoma.
AB  - INTRODUCTION: This study aimed to evaluate the long-term efficacy of
      multimodality therapy for patients with type B3 thymoma. METHODS: A total of 188
      consecutive patients with type B3 were treated in our hospital from January 2001
      to December 2010. One hundred seventy-seven patients who had been treated with
      curative intent were retrospectively analyzed. According to World Health
      Organization Classification, all patients were pathologically confirmed as type
      B3. Distribution of Masaoka stages I, II, III, and IV was 35 (19.8%), 20(11.3%),
      78 (44.1%), and 44 (24.8%), respectively. Myasthenia gravis coexisted in 34% of
      patients. RESULTS: After a mean follow-up of 49 months (7-135 months), the 10
      year overall survival (OS) rates were 65% (89%, 86%, 61%, and 42% in stage I, II,
      III, and IV, respectively). One hundred five patients patients (102 patients with
      R0 resection and 3 with complete response after radiotherapy) were analyzed for
      freedom from recurrence (FFR). The 5- and 10-year FFR rates were 91% and 73%
      (100%, 94%, 84%, 71% and 100%, 94%, 56%, N/A in stages I, II, III, and IV,
      respectively. We have no data of stage IV.) TTP was calculated on 72 patients
      including 57 patients with R+ resection and 15 with partial response or stable
      disease after radiotherapy. The 5-year time-to-progression (TTP) rates were 33%
      (41%, 24% in stage III and IV, respectively). Multivariate analysis showed that
      prognostic factors for OS were the Masaoka stage and adjuvant radiation for
      patients with stage III and IV. The Masaoka stage and resection margin after
      surgery had significant effects on FFR and TTP. CONCLUSION: The type B3 thymoma
      often presented with the later stages at the diagnosis. The Masaoka stage was
      closely associated with OS, FFR, and TTP. Resection margin after surgery was
      related to TTP. Adjuvant radiotherapy may be beneficial to stage III and IV
      patients in this clinical setting.

PMID- 24457244
TI  - NUT midline carcinoma: an aggressive intrathoracic neoplasm.
AB  - Nuclear protein in testis (NUT) midline carcinoma (NMC) is a poorly
      differentiated squamous cell carcinoma that is characterized by a balanced
      translocation between chromosomes 15 and 19 [t(15;19)(q14;p13.1)]. This genetic
      aberration results in the fusion of the NUT gene on chromosome 15 to the
      bromodomain containing 4 (BRD4) gene on chromosome 19. The resultant BRD4-NUT
      fusion oncogene leads to global hypoacetylation and transcriptional repression of
      genes required for differentiation." Although it was first reported in 1991 by
      Kubonishi et al., awareness of this condition remains low and the diagnosis is
      overlooked initially in a number of patients. A 36-year-old man complained of
      cough and right-sided chest pain for 3 weeks before presentation. Imaging studies
      revealed a right hilar mass, and a bronchoscopic biopsy was consistent with an
      aggressive poorly differentiated neoplasm. A combination of cisplatin,
      ifosfamide, and etoposide was administered for two cycles without any
      improvement. A repeat core biopsy showed focal squamous differentiation; and
      given the clinical presentation along with the histologic features, NMC was
      considered in the differential diagnosis. Immunohistochemical staining for NUT
      was positive, and dual-color break-apart fluorescence in situ hybridization
      demonstrated BRD4-NUT rearrangement, thereby confirming a diagnosis of NMC. Our
      patient was subsequently enrolled on a phase 1 clinical trial of a novel, orally
      bioavailable bromodomain and extra terminal inhibitor, GSK525762 (NCT01587703).
      This report illustrates the challenges in diagnosing this rare malignancy, and
      highlights new treatment options for these patients. 

PMID- 24457245
TI  - An unusual cause of Dysphagia in a 76-year-old heavy smoker.

PMID- 24457246
TI  - Surgical treatment of a giant symptomatic cardiac lipoma.

PMID- 24457247
TI  - Acute autoimmune hepatitis, myositis, and myasthenic crisis in a patient with
      thymoma.

PMID- 24457248
TI  - A case of pleural epithelioid sarcoma of proximal type presenting as malignant
      pleural mesothelioma.

PMID- 24457249
TI  - A new KIT gene mutation in thymic cancer and a promising response to imatinib.

PMID- 24457250
TI  - Environmental enrichment modulates glucocorticoid receptor expression and reduces
      anxiety in Indian field male mouse Mus booduga through up-regulation of microRNA
      124a.
AB  - Enriched environmental condition (EC) has been known to reduce anxiety. In this
      study, we examined whether an EC could enhance anxiolytic behavior in the Indian
      field mouse Mus booduga by down-regulating the expression of glucocorticoid
      receptor (GR) through microRNA-124a. Wild individuals were captured at
      agricultural field, and then housed at standard conditions (SC) for 7days. After
      short-term at standard condition (STSC), on 8th day they were divided into three
      groups as those: (i) STSC mice tested on light/dark box on the same day and then
      euthanized to examine gene expression, (ii) maintained at long-term in standard
      condition (LTSC) and (iii) transferred to EC. After 30days, both the LTSC and EC
      groups were tested on the light/dark box and then euthanized to examine gene
      expression in amygdala region of brain. EC group preferred to stay at light
      chamber and exhibited less anxiety-like behavioral components when compared to
      STSC and LTSC groups. However, between the two groups the STSC mice showed lesser
      anxiety-like behavior than LTSC mice. The expression of Dicer, Ago-2 and microRNA
      124a (miR-124a) was more significantly up regulated in EC mice than in STSC and
      LTSC mice. Furthermore, we have demonstrated that miR-124a binds with 3'UTR of
      GR, and subsequently we detected a more decreased level of GR in EC than in STSC,
      LTSC mice. The results suggest that one of the action of EC could be a GR fine
      tuning through miR-124a, but there is no demonstration that it could be the only
      involved molecular mechanism. 

PMID- 24457251
TI  - Seasonal variation of urinary microRNA expression in male goats (Capra hircus) as
      assessed by next generation sequencing.
AB  - Testosterone plays a key role in preparation of a male domesticated goat (Capra
      hircus) to breeding season including changes in the urogenital tract of a male
      goat (buck). microRNAs are important regulators of cellular metabolism,
      differentiation and function. They are powerful intermediaries of hormonal
      activity in the body, including the urogenital tract. We investigated seasonal
      changes in expression of microRNAs in goat buck urine and their potential
      consequences using next generation sequencing (microRNA-Seq). We determined the
      location of each microRNA gene in the goat genome. Testosterone was measured by
      radioimmunoassay and the androgen receptor binding sites (ARBS) in the promoters
      of the microRNA genes were determined by MatInspector. The overall impact of
      regulated microRNAs on cellular physiology was assessed by mirPath. We observed
      high testosterone levels during the breeding season and changes in the expression
      of forty microRNAs. Nineteen microRNAs were upregulated, while twenty-one were
      downregulated. We identified several ARBS in the promoters of regulated
      microRNAs. Notably, the mostly inhibited microRNA, miR-1246, has a unique set of
      several gene copy variants associated with a cluster of androgen receptor binding
      sites. Concomitant changes in regulated microRNA expression could promote
      transcription, proliferation and differentiation of urogenital tract cells.
      Together, these findings indicate that in a domesticated goat (Capra hircus),
      there are specific changes in the microRNA expression profile in buck urine
      during breeding season, which could be attributable to high testosterone levels
      during breeding, and could help in preparation of the urogenital tract for high
      metabolic demands of that season. 

PMID- 24457253
TI  - Associations between severity of motor function and nonmotor symptoms in
      Parkinson's disease: a post hoc analysis of the RECOVER Study.
AB  - BACKGROUND: RECOVER (NCT00474058), a double-blind, placebo-controlled trial in
      patients with Parkinson's disease (PD) and unsatisfactory early-morning motor
      symptom control, demonstrated significant improvements with rotigotine in early
      morning motor function (Unified Parkinson's Disease Rating Scale [UPDRS] III),
      and nocturnal sleep disturbances (modified Parkinson's Disease Sleep Scale [PDSS
      2]), and improvements in nonmotor symptoms (NMS; Non-Motor Symptom Scale [NMSS]).
      METHODS: Post hoc analyses investigated the correlation between motor symptom and
      NMS severity in PD by evaluating associations between UPDRS III and both NMSS and
      PDSS-2 scores. Categories were defined for UPDRS III, NMSS, and PDSS-2 total
      scores; analyses were conducted for the full analysis set (n = 267). RESULTS:
      There was a trend toward increasing PDSS-2 and NMSS total and domain scores with
      increasing UPDRS III category at baseline and end of maintenance (EoM). Pearson
      correlation coefficients between UPDRS III and both NMSS and PDSS-2 total and
      domain scores were r = 0.12-0.44 (r(2) = 0.01-0.19) at baseline, r = 0.05-0.38
      (r(2) = 0.00-0.14) at EoM, and r = -0.02-0.36 (r(2) = 0.00-0.13) for change from
      baseline to EoM. CONCLUSION: There was only a small correlation between severity
      of early-morning motor symptoms and overall burden of NMS and nocturnal sleep
      disturbances in RECOVER, suggesting that motor symptoms and NMS originate, at
      least partly, from distinct pathophysiological pathways.

PMID- 24457254
TI  - Gestational weight gain in twin pregnancies and maternal and child health: a
      systematic review.
AB  - Our objective was to systematically review the data interrogating the association
      between gestational weight gain (GWG) and maternal and child health among women
      with twin gestations. We identified 15 articles of twin gestations that studied
      GWG in relation to a maternal, perinatal or child health outcome and controlled
      for gestational age at delivery and prepregnancy body mass index. A positive
      association between GWG and fetal size was consistently found. Evidence on
      preterm birth and pregnancy complications was inconsistent. The existing studies
      suffer from serious methodological weaknesses, including not properly accounting
      for the strong correlation between gestational duration and GWG and not
      controlling for chorionicity. In addition, serious perinatal outcomes were not
      studied, and no research is available on the association between GWG and outcomes
      beyond birth. Our systematic review underscores that GWG in twin gestations is a
      neglected area of research. Rigorous studies are needed to inform future evidence
      based guidelines. 

PMID- 24457255
TI  - Cannabis, the pregnant woman and her child: weeding out the myths.
AB  - To review and summarise the literature reporting on cannabis use within western
      communities with specific reference to patterns of use, the pharmacology of its
      major psychoactive compounds, including placental and fetal transfer, and the
      impact of maternal cannabis use on pregnancy, the newborn infant and the
      developing child. Review of published articles, governmental guidelines and data
      and book chapters. Although cannabis is one of the most widely used illegal
      drugs, there is limited data about the prevalence of cannabis use in pregnant
      women, and it is likely that reported rates of exposure are significantly
      underestimated. With much of the available literature focusing on the impact of
      other illicit drugs such as opioids and stimulants, the effects of cannabis use
      in pregnancy on the developing fetus remain uncertain. Current evidence indicates
      that cannabis use both during pregnancy and lactation, may adversely affect
      neurodevelopment, especially during periods of critical brain growth both in the
      developing fetal brain and during adolescent maturation, with impacts on
      neuropsychiatric, behavioural and executive functioning. These reported effects
      may influence future adult productivity and lifetime outcomes. Despite the
      widespread use of cannabis by young women, there is limited information available
      about the impact perinatal cannabis use on the developing fetus and child,
      particularly the effects of cannabis use while breast feeding. Women who are
      using cannabis while pregnant and breast feeding should be advised of what is
      known about the potential adverse effects on fetal growth and development and
      encouraged to either stop using or decrease their use. Long-term follow-up of
      exposed children is crucial as neurocognitive and behavioural problems may
      benefit from early intervention aimed to reduce future problems such as
      delinquency, depression and substance use. 

PMID- 24457258
TI  - Integration of length and curvature in haptic perception.
AB  - We investigated if and how length and curvature information are integrated when
      an object is explored in one hand. Subjects were asked to explore four types of
      objects between thumb and index finger. Objects differed in either length,
      curvature, both length and curvature correlated as in a circle, or anti
      correlated. We found that when both length and curvature are present, performance
      is significantly better than when only one of the two cues is available.
      Therefore, we conclude that there is integration of length and curvature.
      Moreover, if the two cues are correlated in a circular cross-section instead of
      in an anti-correlated way, performance is better than predicted by a combination
      of two independent cues. We conclude that integration of curvature and length is
      highly efficient when the cues in the object are combined as in a circle, which
      is the most common combination of curvature and length in daily life. 

PMID- 24457256
TI  - Inflammatory markers in cord blood or maternal serum for early detection of
      neonatal sepsis-a systemic review and meta-analysis.
AB  - OBJECTIVE: To perform a quantitative review of the evidence on the diagnostic
      value of inflammatory markers in maternal serum or umbilical cord blood for the
      diagnosis of early-onset neonatal sepsis (EONS). STUDY DESIGN: We searched
      multiple databases for studies published through March 2013 that evaluated the
      diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and
      interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either
      umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test
      performance characteristics with the use of forest plots, hierarchical summary
      receiver operating characteristic curves and bivariate random effects models.
      RESULT: Our search identified 3874 citations, of which 15 studies evaluating 2178
      episodes of suspected neonatal infection were included for analysis. IL-6 in cord
      blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence
      interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and
      IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a
      valid rule-in test. IL-6 in cord blood with a LR- of 0.10 (0.05 to 0.21) and PCT
      in cord blood with a LR- of 0.20 (0.12-0.37) can be qualified as a useful rule
      out test. Either CRP or WBC was inadequate for diagnosis of EONS. CONCLUSION: For
      cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool.
      For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An
      interventional study may be needed to answer whether the addition of these tests
      will improve the outcome of patients with EONS.

PMID- 24457257
TI  - Sex differences in cerebral blood flow following chorioamnionitis in healthy term
      infants.
AB  - OBJECTIVE: Sex is an important determinant of neonatal outcomes and may have a
      significant role in the physiologic response to maternal chorioamnionitis. Our
      goal was to determine cerebral blood flow (CBF) parameters by sex and subsequent
      neurodevelopment in healthy term infants exposed to chorioamnionitis. STUDY
      DESIGN: CBF by Doppler ultrasound in anterior and middle cerebral (ACA, MCA) and
      basilar arteries were analyzed for time-averaged maximum velocity (TAMX) and
      corrected resistive index in 52 term control and chorioamnionitis-exposed infants
      between 24 and 72 h after birth. Placental pathology confirmed histologic
      evidence of chorioamnionitis (HC). Bayley Scales of Infant Development-III were
      administered at 12 months. RESULT: HC male infants had significantly greater TAMX
      in the MCA and lower mean MCA and ACA resistance than HC females. Abnormal CBF
      correlated negatively with neurodevelopmental outcome. CONCLUSION: CBF is altered
      in term infants with histologically confirmed chorioamnionitis compared with
      control infants with sex-specific differences.

PMID- 24457260
TI  - Perspectives on the evolution, assembly and conformational dynamics of fatty acid
      synthase type I (FAS I) systems.
AB  - Recently, atomic models of the mammalian, fungal and the bacterial fatty acid
      synthases type I (FAS I) were reported. Now, a wealth of functional data,
      collected during the last decades, can be embedded into structural frames. But
      there is more, which remains to be done! Our current considerations are
      implicitly very much based on a static view onto these proteins. The next step is
      to include the dynamic processes, which are essential for the function of FAS I.
      In this perspective, aspects of the current knowledge are reviewed and presented
      as the basis for the scientific challenges in a new epoch of FAS research. 

PMID- 24457259
TI  - Effects of mesenchymal stem cells transplanted at different time points in a rat
      remnant kidney model.
AB  - AIMS: The optimal time for mesenchymal stem cell (MSCs) transplantation remains
      an unresolved issue. We compared the effects of MSCs on a rat remnant kidney
      model. METHODS: Male Sprague-Dawley rats were randomly divided and treated with a
      corresponding reagent at 4, 8, 12 and 16 weeks, respectively. A remnant kidney
      model was established and MSCs were injected into rats. The migration of MSCs was
      then assessed by using cell-tracking experiments. Renal function and histological
      analyses were performed 4 weeks after MSC transplantation. Immunohistochemistry,
      Western blotting and real-time polymerase chain reaction were used to detect the
      TGF-beta1 and alpha-SMA levels. RESULTS: Four weeks after MSC injection, MSCs
      were found to migrate to the injured kidney. Significant histological damage
      improvement was observed after the treatment of MSCs at 4 and 8 weeks. The
      functional benefits of MSC treatment were observed in the 5/6 nephrectomy (Nx) +
      MSC group and the benefits were significantly higher at 4 and 8 weeks than at
      other time points (p < 0.05). Meanwhile, serum creatinine and urea levels as well
      as glomerular sclerosis and tubulointerstitial injury indexes were decreased at 4
      and 8 weeks. Compared with the 5/6 Nx + PBS group, TGF-beta1 and alpha-SMA levels
      were decreased in the 5/6 Nx + MSC group. CONCLUSION: These data can be used to
      optimize the MSC transplantation time point as a therapeutic modality.

PMID- 24457261
TI  - A comparative kinematic analysis of cyclical bending in patients with early
      stages of Parkinson's disease and in patients with essential tremor.
AB  - Early stage Parkinson's disease (PD) shares certain symptoms with essential
      tremor (ET), which makes it difficult to differentiate between the two. We
      analyzed cyclical body bends to find kinematic parameters that are capable of
      differentiating among PD, ET and normal control (NC) subjects. A linear
      discriminant analysis of the joint angles showed a reliable distinction between
      NC and the two groups of patients, while differentiating reasonably well between
      PD and ET. PD patients showed difficulty performing hip segment rotation around
      the vertical axis, whereas ET patients demonstrated enlarged torso sway in the
      frontal plane. These findings suggest that kinematic parameters of body movement
      in the standing position are sensitive enough to serve as subclinical marks in
      the early diagnosis of PD and ET. 

PMID- 24457262
TI  - Nano-engineering thermal transport performance of carbon nanotube networks with
      polymer intercalation: a molecular dynamics study.
AB  - Based on polymer perfusion behaviour inside carbon nanotube (CNT) networks, the
      thermal transport performances of the CNT networks with various extents of
      polymer intercalation are studied by dividing them into two parts: thermal
      transport at the tube contact interfaces of CNT junctions and along the tube
      axis. The thermal transport performance at the tube contact interfaces of CNT
      junctions is similar to that in the transverse direction of graphene layers.
      Hence, to obtain a fundamental understanding of thermal transport performance at
      the tube contact interfaces, thermal conductance along the z-axis direction of
      graphene layers with and without polymer intercalation is investigated using a
      non-equilibrium molecular dynamics (MD) simulation method. Thermal conductivity
      along the tube axis direction of the polymer wrapped CNT is also calculated using
      the same method. The simulation results show that a low extent of polymer
      aggregation at the tube contact interfaces can significantly improve the
      interfacial thermal conductance. However, when the polymer content at the tube
      contact interfaces exceeds a critical fraction, the interfacial thermal
      conductance is decreased. The results also indicate that the polymer molecules
      wrapping around the CNT walls have a strong negative influence on the bulk
      thermal conductivity of the CNT along its axis direction. 

PMID- 24457263
TI  - Limitations of body surface area-based activity calculation for radioembolization
      of hepatic metastases in colorectal cancer.
AB  - PURPOSE: To calculate absorbed radiation doses in patients treated with resin
      microspheres prescribed by the body surface area (BSA) method and to analyze dose
      response and toxicity relationships. MATERIALS AND METHODS: A retrospective
      review was performed of 45 patients with colorectal carcinoma metastases who
      received single-session whole-liver resin microsphere radioembolization.
      Prescribed treatment activity was calculated using the BSA method. Liver volumes
      and whole-liver absorbed doses (D(WL)) were calculated. D(WL) was correlated with
      toxicity and radiographic and biochemical response. RESULTS: The standard BSA
      based administered activity (range, 0.85-2.58 GBq) did not correlate with D(WL)
      (mean, 50.4 Gy; range, 29.8-74.7 Gy; r = -0.037; P = .809) because liver weight
      was highly variable (mean, 1.89 kg; range, 0.94-3.42 kg) and strongly correlated
      with D(WL) (r = -0.724; P < .001) but was not accounted for in the BSA method.
      Patients with larger livers were relatively underdosed, and patients with smaller
      livers were relatively overdosed. Patients who received D(WL) > 50 Gy experienced
      more toxicity and adverse events (> grade 2 liver toxicity, 46% vs 17%; P < .05)
      but also responded better to the treatment than patients who received D(WL)< 50
      Gy (disease control, 88% vs 24%; P < .01). CONCLUSIONS: Using the standard BSA
      formula, the administered activity did not correlate with D(WL). Based on this
      short-term follow-up after salvage therapy in patients with late stage metastatic
      colorectal carcinoma, dose-response and dose-toxicity relationships support using
      a protocol based on liver volume rather than BSA to prescribe the administered
      activity.

PMID- 24457264
TI  - Karyotype and chromosome variability in the armadillo Chaetophractus villosus in
      Argentina.
AB  - Karyotype and cytotype variations for the large hairy armadillo (Chaetophractus
      villosus) were studied throughout the species' Argentine distribution. Peripheral
      blood lymphocyte cultures of 421 animals were used to obtain mitotic metaphases.
      Preparations were subjected to conventional staining, G- and C-banding, and FISH
      involving a telomeric probe. Meiotic analysis was performed on testis material
      from 10 adults. Spermatocytes were examined for synaptonemal complexes in
      microspreads. The karyotype (2n = 60 XX/XY; FN = 84 without XY) showed an
      autosomal complement of 6 metacentric and 7 submetacentric chromosomes; the
      remainder was acrocentric. The X chromosome was submetacentric and the Y
      acrocentric. Centromeric C+ marks were observed in all chromosomes except pair
      16. Three NOR signals were detected in 6q, 12p, and 26p. Two chromosomal
      rearrangements were characterized in chromosome pair 1 a pericentric inversion
      seen in the material from Jacinto Arauz, General Madariaga and Pellegrini and a
      deletion in the material from Loma Verde. Interstitial telomeric signals were
      observed in chromosome pairs 4, 12, 16, and 26. Pachytene spermatocyte analysis
      confirmed the basic chromosome number and morphologies observed in mitotic
      karyotypes. The evolution of C. villosus involved chromosomal rearrangements as
      recorded for other species of its superorder. The present results establish the
      basis for the cytogenetic characterization of this species.

PMID- 24457265
TI  - Novel lung adenocarcinoma and nuclear factor-kappa B (NF-kappaB) inhibitors:
      synthesis and evaluation of lantadene congeners.
AB  - The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A
      (3), B (4) and 22beta-hydroxyoleanolic acid (5) were synthesized and were tested
      in vitro for their NF-kappaB and IKKbeta inhibitory potencies and cytotoxicity
      against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56
      and 0.42 MUmol, respectively against TNF-alpha induced activation of NF-kappaB.
      The congeners 12 and 13 exhibited inhibition of IKKbeta in a single-digit
      micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity
      against A549 lung cancer cells with IC50 of 0.12 and 0.08 MUmol, respectively.
      The lead ester congeners were stable in the acidic pH, while hydrolyzed readily
      in the human blood plasma to release the active parent moieties.

PMID- 24457266
TI  - Definition of psychosomatic medicine and the applicability of DSM-IV-TR to
      outpatients visiting a Japanese psychosomatic clinic.

PMID- 24457267
TI  - Tissue engineered esophagus scaffold constructed with porcine small intestinal
      submucosa and synthetic polymers.
AB  - Acellular porcine small intestinal submucosa (SIS) has been successfully used for
      reconstructing esophagus with half circumferential defects. However, repairing
      full circumferential esophageal defects with SIS has been restricted due to the
      latter's poor mechanical properties. In the present study, synthetic polyesters
      biomaterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and
      poly(lactide-co-glycolide) (PLGA) have been used to improve the mechanical
      properties of SIS. Feasibility of SIS/PHBHHx-PLGA composite material scaffold for
      esophageal tissue engineering has been assessed through a series of testing. The
      appropriate mixing ratio of PHBHHx and PLGA polymers has been determined as 5:5
      by mechanical testing and in vitro degradation experiment. The morphology of
      constructed membranous and tubular scaffolds was also characterized. As confirmed
      by enzyme-linked immunosorbent assay, the contents of VEGF and TGF-beta have
      respectively reached 657 +/- 18 ng mL(-1) and 130 +/- 4 pg mL(-1) within the
      SIS/PHBHHx-PLGA specimens. Biocompatibility of the SIS/PHBHHx-PLGA specimens with
      rat bone marrow mesenchymal stem cells (MSCs) was also evaluated by scanning
      electron microscopy and a live-dead cell viability assay. Actin filaments of MSCs
      on the composite materials were labeled. Biological safety of the extract from
      SIS/PHBHHx-PLGA specimens, measured as hemolysis rate, was all lower than 5%.
      Compared with SIS and SIS/PHBHHx-PLGA specimens, inflammatory reaction provoked
      by the PHBHHx-PLGA specimens in rats was however more severe. Our results have
      suggested that SIS/PHBHHx-PLGA composite material can offer a new approach for
      esophageal tissue engineering.

PMID- 24457268
TI  - Design and analysis of temperature preference behavior and its circadian rhythm
      in Drosophila.
AB  - The circadian clock regulates many aspects of life, including sleep, locomotor
      activity, and body temperature (BTR) rhythms(1) (,) (2). We recently identified a
      novel Drosophila circadian output, called the temperature preference rhythm
      (TPR), in which the preferred temperature in flies rises during the day and falls
      during the night (3). Surprisingly, the TPR and locomotor activity are controlled
      through distinct circadian neurons(3). Drosophila locomotor activity is a well
      known circadian behavioral output and has provided strong contributions to the
      discovery of many conserved mammalian circadian clock genes and mechanisms(4).
      Therefore, understanding TPR will lead to the identification of hitherto unknown
      molecular and cellular circadian mechanisms. Here, we describe how to perform and
      analyze the TPR assay. This technique not only allows for dissecting the
      molecular and neural mechanisms of TPR, but also provides new insights into the
      fundamental mechanisms of the brain functions that integrate different
      environmental signals and regulate animal behaviors. Furthermore, our recently
      published data suggest that the fly TPR shares features with the mammalian
      BTR(3). Drosophila are ectotherms, in which the body temperature is typically
      behaviorally regulated. Therefore, TPR is a strategy used to generate a rhythmic
      body temperature in these flies(5-8). We believe that further exploration of
      Drosophila TPR will facilitate the characterization of the mechanisms underlying
      body temperature control in animals.

PMID- 24457269
TI  - Headache from the doctors' perspective.
AB  - BACKGROUND: General practitioners (GPs) and neurologists are involved in treating
      headache patients in Portugal. Having migraine themselves might influence the way
      they perceive and treat migraine patients. OBJECTIVE: To identify clinicians'
      perceptions about migraine, their own headache status and management of their own
      migraine. METHODS: An observational cross-sectional survey of GPs and
      neurologists using anonymous questionnaires including demographic data, headache
      and migraine status and migraine perception questions. RESULTS: Of 348 respondent
      physicians, 20% were neurologists and 53% were females with an average age of 48
      years. The majority had an interest in migraine and considered it disabling
      (93%), although 65-85% reported management difficulties, GPs more often than
      neurologists. Satisfaction with current treatment options was high (69-79%). 63
      physicians suffered from migraine and 81% felt it influenced their perception of
      the disease. Portuguese physicians preferentially treat their own migraines with
      NSAIDs (33%), analgesics (29%) and triptans (20%). CONCLUSION: Portuguese
      physicians treating migraine patients have realistic perceptions about the
      disease and those with migraine feel their perception is influenced by their
      experience. Although reporting management difficulties, the majority of
      physicians are satisfied with current treatment options for migraine.

PMID- 24457270
TI  - Crystallization of molecular systems from solution: phase diagrams,
      supersaturation and other basic concepts.
AB  - The aim of the tutorial review is to show that any crystallization from solution
      is guided by stable or metastable equilibria and thus can be rationalized by
      using phase diagrams. Crystallization conducted by cooling, by evaporation and by
      anti-solvent addition is mainly considered. The driving force of crystallization
      is quantified and the occurrence of transient metastable states is logically
      explained by looking at the pathways of crystallization and the progressive
      segregation which might occur in a heterogeneous system. 

PMID- 24457271
TI  - Innovations, inventions and improvements.

PMID- 24457272
TI  - Review and recommendations on the current practice of meta-analyses: a guide to
      appraise the evidence.

PMID- 24457273
TI  - The quickening path ahead for renal denervation therapies?

PMID- 24457274
TI  - 2014, a new year of challenges and accomplishments.

PMID- 24457275
TI  - What the interventionalist should know about renal denervation in hypertensive
      patients: a position paper by the ESH WG on the interventional treatment of
      hypertension.
AB  - Percutaneous catheter-based transluminal renal denervation (RDN) has emerged as a
      new approach to achieve sustained blood pressure reduction in patients with drug
      resistant hypertension. Experts from ESH and ESC in their recently released
      position papers and consensus document have summarised the current evidence,
      unmet needs and practical recommendations for the application of this therapeutic
      strategy in clinical practice. Experts of the ESH Working Group for the
      interventional treatment of hypertension prepared this position paper in order to
      provide interventionalists with guidance through the procedure of RDN. Given that
      there is no established intraprocedural control of ablation success,
      interventionalists have to be familiar with the aspects related to the anatomy
      and imaging of the renal arteries, the distribution of renal sympathetic fibres,
      the special equipment necessary for RDN and the procedural details in order to
      maximise the success and minimise potential complications. 

PMID- 24457276
TI  - Nicorandil prevents microvascular dysfunction resulting from PCI in patients with
      stable angina pectoris: a randomised study.
AB  - AIMS: Nicorandil, an ATP sensitive potassium channel opener, may reduce the
      incidence of microvascular dysfunction after percutaneous coronary intervention
      (PCI) by dilating coronary resistance vessels. The aim of the study was
      evaluation of the impact of the administration of intravenous nicorandil on
      measuring the index of microcirculatory resistance (IMR) in PCI to patients with
      stable angina pectoris (SAP). METHODS AND RESULTS: Intravascular ultrasound
      (IVUS), fractional flow reserve (FFR), IMR and blood examination (CK-MB), cardiac
      troponin I (cTnI) immediately post-PCI (and 24 hours later) were performed in 62
      consecutive patients with SAP undergoing PCI. FFR and IMR were measured
      simultaneously with a single coronary pressure wire. IMR was defined as
      Pd/coronary flow (or Pd* mean transit time) at peak hyperaemia. Patients were
      randomised to the control (n=29), or nicorandil group (n=33). In the nicorandil
      group, nicorandil was intravenously administered as a 6 mg bolus injection just
      before PCI and as a constant infusion at 6 mg/hour for 24 hours thereafter. All
      volumetric IVUS parameters and FFR were similar between the two groups both pre-
      and post-PCI. However, IMR immediately post-PCI and cTnI 24 hours post-PCI were
      significantly higher in the control group compared to the nicorandil group (IMR:
      25.4+/-12.1 vs. 17.9+/-9.1 units, and cTnI: 0.21+/-0.13 vs. 0.12+/-0.08 ng/mL,
      for control vs. nicorandil). The incidence for cTnI elevation more than fivefold
      the normal range (>0.20 ng/mL) was significantly larger in the control group than
      in the nicorandil group (41% vs. 12%, p<0.01). Additionally, the control group
      showed a closer correlation between plaque volume reduction during stenting as
      assessed by volumetric IVUS, and cTnI elevation than the nicorandil group (r=0.55
      vs. 0.42, p<0.001 for control vs. nicorandil). CONCLUSIONS: In patients
      undergoing successful coronary stenting for stable angina, administration of
      nicorandil is associated with reduced microvascular dysfunction induced by PCI.

PMID- 24457277
TI  - Thrombus aspiration during primary percutaneous coronary intervention for
      preserving the index of microcirculatory resistance: a randomised study.
AB  - AIMS: We aimed to investigate whether thrombus aspiration could preserve the
      index of microcirculatory resistance (IMR) after primary percutaneous coronary
      intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).
      METHODS AND RESULTS: Sixty-three patients with STEMI were randomised into two
      groups: primary PCI after thrombus aspiration (aspiration group, n=33) and
      primary PCI without thrombus aspiration (non-aspiration group, n=30). IMR was
      measured using a pressure-temperature sensor-tipped coronary wire.
      Echocardiography was performed at baseline and at six-month follow-up. No
      significant differences in baseline ejection fraction (EF, 47.3+/-8.5% vs. 49.5+/
      7.8%, p=0.281) and baseline wall motion score index (WMSI, 1.45+/-0.31 vs. 1.37+/
      0.27, p=0.299) were observed between the two groups. However, significant
      differences in IMR (23.5+/-10.2 U vs. 34.2+/-21.7 U, p=0.018), %E2%88%86EF
      (follow-up EF - baseline EF; 3.33+/-4.6% vs. 0.73+/-1.9%, p=0.005), and
      %E2%88%86WMSI (follow-up WMSI - baseline WMSI; -0.121+/-0.16 vs. -0.004+/-0.07,
      p=0.001) were observed between the two groups. CONCLUSIONS: Thrombus aspiration
      as an adjunctive method to primary PCI for STEMI may preserve microvascular
      integrity and have beneficial effects on myocardial microcirculation.

PMID- 24457278
TI  - Influence of epicardial stenosis severity and central venous pressure on the
      index of microcirculatory resistance in a follow-up study.
AB  - AIMS: This study sought to evaluate the reproducibility of the index of
      microcirculatory resistance (IMR) in a follow-up model and the role of epicardial
      artery stenosis and central venous pressure (Pv) on IMR. METHODS AND RESULTS:
      Twenty-two patients with stable coronary artery disease underwent coronary
      catheterisation at baseline and after seven weeks. The IMR was calculated at
      baseline and follow-up in several ways: as IMRuncorrected=Pd.Tmn (Pd:
      intracoronary pressure distal to the stenosis; Tmn: transit mean time);
      IMRcorrected=Pa.Tmn.(Pd - Pw)/(Pa-Pw), (Pw: coronary wedge pressure; Pa: aortic
      pressure); and as IMRcentral venous pressure (IMRcvp)=(Pa-Pv).Tmn.(Pd-Pw)/(Pa
      Pw). By neglecting Pw, IMR was overestimated irrespective of the haemodynamic
      severity of the epicardial stenosis (baseline: IMRuncorrected=15.5+/-8.9 U vs.
      IMRcorrected=13.5+/-8 U, p<0.001; follow-up: IMRuncorrected=16.9+/-4.9 U vs.
      IMRcorrected=13.8+/-4.6 U, p<0.001). In the intra-individual analysis IMR did not
      differ between the two time points. The IMRcvp equalled the IMRcorrected at all
      time points. CONCLUSIONS: IMR is a reproducible index in follow-up studies,
      independent of any overestimation existing when collateral flow status is
      neglected. Pv can be neglected for calculation of the IMR.

PMID- 24457279
TI  - Reference interval for the index of coronary microvascular resistance.
AB  - AIMS: The index of microvascular resistance (IMR) is a relatively new tool that
      is used to assess microvascular function during routinely performed left heart
      catheterisations. In order to establish a reference interval for IMR, we
      investigated a subset of arrhythmia patients with structurally normal hearts and
      no or minimal coronary artery disease. METHODS AND RESULTS: Physiological
      variables, including IMR, were measured in 20 otherwise healthy patients aged 40
      60 years (10 males and 10 females) who had been referred for electrophysiological
      evaluation of suspected atrioventricular nodal re-entry tachycardia. IMR values
      were non-normally distributed with a median value of 12.6. We established a
      reference interval, that would be relevant to 95% of the population, of 7.3 (90%
      CI: 6.6-8.0) - 27.2 (90% CI: 20.8-33.7), using Box-Cox transformation and the
      robust Horn method. Spearman's rank correlation analysis revealed no significant
      relationship between IMR and several different variables. CONCLUSIONS: A
      reference interval for IMR was established in a population of patients aged 40-60
      years with structurally normal hearts, considered to be representative of the
      general population. IMR was not related to sex, age or any of the other variables
      tested, suggesting that this reference range can be applied to the general
      population.

PMID- 24457280
TI  - Gender, TIMI risk score and in-hospital mortality in STEMI patients undergoing
      primary PCI: results from the Belgian STEMI registry.
AB  - AIMS: The relationship between the predictive performance of the TIMI risk score
      for STEMI and gender has not been evaluated in the setting of primary PCI (pPCI).
      Here, we compared in-hospital mortality and predictive performance of the TIMI
      risk score between Belgian women and men undergoing pPCI. METHODS AND RESULTS: In
      hospital mortality was analysed in 8,073 (1,920 [23.8%] female and 6,153 [76.2%]
      male patients) consecutive pPCI-treated STEMI patients, included in the
      prospective, observational Belgian STEMI registry (January 2007 to February
      2011). A multivariable logistic regression model, including TIMI risk score
      variables and gender, evaluated differences in in-hospital mortality between men
      and women. The predictive performance of the TIMI risk score according to gender
      was evaluated in terms of discrimination and calibration. Mortality rates for
      TIMI scores in women and men were compared. Female patients were older, had more
      comorbidities and longer ischaemic times. Crude in-hospital mortality was 10.1%
      in women vs. 4.9% in men (OR 2.2; 95% CI: 1.82-2.66, p<0.001). When adjusting for
      TIMI risk score variables, mortality remained higher in women (OR 1.47, 95% CI:
      1.15-1.87, p=0.002). The TIMI risk score provided a good predictive
      discrimination and calibration in women as well as in men (c-statistic=0.84 [95%
      CI: 0.809-0.866], goodness-of-fit p=0.53 and c-statistic=0.89 [95% CI: 0.873
      0.907], goodness-of-fit p=0.13, respectively), but mortality prediction for TIMI
      scores was better in men (p=0.02 for TIMI score x gender interaction).
      CONCLUSIONS: In the Belgian STEMI registry, pPCI-treated women had a higher in
      hospital mortality rate even after correcting for TIMI risk score variables. The
      TIMI risk score was effective in predicting in-hospital mortality but performed
      slightly better in men. The database was registered with clinicaltrials.gov
      (NCT00727623).

PMID- 24457281
TI  - Medication non-adherence as a critical factor in the management of presumed
      resistant hypertension: a narrative review.
AB  - AIMS: Medication non-adherence is a crucial behavioural risk factor in
      hypertension management. Forty-three to 65.5% of patients with presumed resistant
      hypertension are non-adherent. This narrative review focuses on the definition of
      adherence/non-adherence, measurement of medication adherence, and the management
      of medication non-adherence in resistant hypertension using multilevel
      intervention approaches to prevent or remediate non-adherence. METHODS AND
      RESULTS: A review of adherence and resistant hypertension literature was
      conducted. Medication adherence consists of three different yet related
      dimensions: initiation, implementation, and discontinuation. To effectively
      measure medication non-adherence, a combination of direct and indirect methods is
      optimal. Interventions to tackle medication non-adherence must be integrated in
      multilevel approaches. Interventions at the patient level can combine
      educational/cognitive (e.g., patient education), behavioural/counselling (e.g.,
      reducing complexity, cueing, tailoring to patient's lifestyle) and
      psychological/affective (e.g., social support) approaches. Improving provider
      competencies (e.g., reducing regimen complexity), implementing new care models
      inspired by principles of chronic illness management, and interventions at the
      healthcare system level can be combined. CONCLUSIONS: Improvement of patient
      outcomes in presumed resistant hypertension will only be possible if the
      behavioural dimensions of patient management are fully integrated at all levels.

PMID- 24457282
TI  - Intracoronary versus intravenous bolus abciximab administration in patients
      undergoing primary percutaneous coronary intervention with acute ST-elevation
      myocardial infarction: a pooled analysis of individual patient data from five
      randomised controlled trials.
AB  - AIMS: In recent years, intracoronary bolus abciximab has emerged as an
      alternative to the standard intravenous route in patients with ST-elevation
      myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (PCI). The aim of the current study was to perform an individual
      patient-level pooled analysis of randomised trials, comparing intracoronary
      versus intravenous abciximab bolus use in STEMI patients undergoing primary PCI.
      METHODS AND RESULTS: Individual data of 3,158 patients enrolled in five trials
      were analysed. Reperfusion endpoints were: post-procedural Thrombolysis in
      Myocardial Infarction (TIMI) 3 flow, myocardial blush grade (MBG) 2/3 and
      complete ST-segment resolution. The primary clinical endpoint of interest was the
      composite of death and reinfarction at 30 days. Compared with the intravenous
      route, intracoronary abciximab bolus administration did not improve TIMI 3 flow
      (odds ratio [OR] 1.19; 95% confidence interval [CI]: 0.90-1.59; p=0.23) and
      complete ST-segment resolution (OR 1.22, 95% CI: 0.92-1.63, p=0.17), but
      increased MBG 2/3 occurrence (OR 1.83, 95% CI: 1.05-3.18, p=0.03). At 30-day
      follow-up, intracoronary bolus abciximab did not reduce the risk of death and
      reinfarction (OR 0.78, 95% CI: 0.55-1.10, p=0.16), death (OR 0.77, 95% CI: 0.51
      1.17, p=0.22), reinfarction (OR 0.79, 95% CI: 0.46-1.33, p=0.38) and stent
      thrombosis (OR 0.77, 95% CI: 0.43-1.35, p=0.36) as compared with intravenous
      administration. CONCLUSIONS: In STEMI patients undergoing primary PCI,
      intracoronary abciximab does not provide additional benefits as compared with
      standard intravenous treatment and, therefore, it should not be recommended as
      the default route of administration in this setting.

PMID- 24457283
TI  - How should I treat a symptomatic post dissection carotid aneurysm?

PMID- 24457284
TI  - Tools and techniques clinical: percutaneous intervention of calcific coronary
      lesions.

PMID- 24457286
TI  - Biomarkers in growth.
AB  - BACKGROUND: The current approaches to assess growth are limited to anthropometry,
      are insensitive and nonspecific, and do not enable an improved understanding of
      how nutrition might impact growth. Consequently, new tools to develop better
      standards of care and programs to address ongoing concerns about nutrition and
      health are needed. METHODS: The Biomarkers of Nutrition for Development (BOND)
      project is designed to support the discovery, development, and use of current and
      new biomarkers of nutritional exposure, status, function, and effect. The
      Biomarkers in Growth (BIG) project was initiated as a BOND program to develop a
      roadmap for moving the nutrition and growth agenda forward. The first step in
      this project was a session jointly organized by the BOND Secretariat and Sight
      and Life at the 20th International Congress on Nutrition in Granada, Spain.
      RESULTS: The BIG session outlined current approaches to evaluating growth and
      understanding of the role of nutrition in linear growth, body composition, and
      long-term health outcomes and the potential role of systems biology in the
      assessment of the nutrition-growth relationship. CONCLUSION: The session
      presentations and deliberations highlighted the need for a concerted effort to
      address the critical gaps in our understanding of the biology and assessment of
      growth.

PMID- 24457287
TI  - Trauma and transfusion.

PMID- 24457285
TI  - Impaired fear memory specificity associated with deficient endocannabinoid
      dependent long-term plasticity.
AB  - In addition to its central role in learning and memory, N-methyl D-aspartate
      receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse
      maturation and has been implicated in schizophrenia. We have transiently induced
      NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing
      fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC)
      in adult mice. We show that transient NMDAR hypofunction during early brain
      development, coinciding with the maturation of cortical plasticity results in a
      loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD)
      at adult central glutamatergic synapses, while another form of presynaptic long
      term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3
      LTD) remains intact. Mice with this selective impairment of presynaptic
      plasticity also showed deficits in fear memory specificity. The observed deficit
      in cortical presynaptic plasticity may represent a neural maladaptation
      contributing to network instability and abnormal cognitive functioning. 

PMID- 24457288
TI  - Approaches to understanding the impact of technologies for aging in place: a mini
      review.
AB  - BACKGROUND: There are many approaches to evaluating aging-in-place technologies.
      While there are standard measures for outcomes such as health and caregiver
      burden, which lend themselves to statistical analysis, researchers have a harder
      time identifying why a particular information and communication technology (ICT)
      intervention worked (or not). OBJECTIVE: The purpose of this paper is to review a
      variety of methods that can help answer these deeper questions of when people
      will utilize an ICT for aging in place, how they use it, and most importantly
      why. This review is sensitive to the special context of aging in place, which
      necessitates an evaluation that can explore the nuances of the experiences of
      older adults and their caregivers with the technology in order to fully
      understand the potential impact of ICTs to support aging in place. METHODS: The
      authors searched both health (PubMed) and technology (ACM Digital Library)
      venues, reviewing 115 relevant papers that had an emphasis on understanding the
      use of aging-in-place technologies. This mini-review highlights a number of
      popular methods used in both the health and technology fields, including
      qualitative methods (e.g. interviews, focus groups, contextual observations,
      diaries, and cultural probes) and quantitative methods (e.g. surveys, the
      experience sampling method, and technology logs). RESULTS: This review highlights
      that a single evaluation method often is not adequate for understanding why
      people adopt ICTs for aging in place. The review ends with two examples of
      multifaceted evaluations attempting to get at these deeper issues. CONCLUSION:
      There is no proscriptive formula for evaluating the intricate nuances of
      technology acceptance and use in the aging-in-place context. Researchers should
      carefully examine a wide range of evaluation techniques to select those that will
      provide the richest insights for their particular project.

PMID- 24457289
TI  - X-ray ptychographic computed tomography at 16 nm isotropic 3D resolution.
AB  - X-ray ptychography is a scanning variant of coherent diffractive imaging with the
      ability to image large fields of view at high resolution. It further allows
      imaging of non-isolated specimens and can produce quantitative mapping of the
      electron density distribution in 3D when combined with computed tomography. The
      method does not require imaging lenses, which makes it dose efficient and
      suitable to multi-keV X-rays, where efficient photon counting, pixelated
      detectors are available. Here we present the first highly resolved quantitative X
      ray ptychographic tomography of an extended object yielding 16 nm isotropic 3D
      resolution recorded at 2 A wavelength. This first-of-its-kind demonstration paves
      the way for ptychographic X-ray tomography to become a promising method for X-ray
      imaging of representative sample volumes at unmatched resolution, opening
      tremendous potential for characterizing samples in materials science and biology
      by filling the resolution gap between electron microscopy and other X-ray imaging
      techniques. 

PMID- 24457290
TI  - Parkinson's disease is associated with greater regularity of repetitive voluntary
      movements.
AB  - Bradykinesia is a cardinal symptom of Parkinson's disease (PD). Both aging and
      disease are shown to be associated with decreased adaptability to environmental
      stresses characterized by reduced complexity (or increased regularity) of
      biorhythms. The purpose of this study was to investigate the regularity of
      movement in individuals with PD, and the effect of dopaminergic medication. Nine
      subjects with PD and eight controls performed wrist flexion/extension movements
      at maximal velocity and range of motion. Subjects with PD were tested under two
      medication conditions. Approximate entropy (ApEn) was calculated to assess the
      regularity of the movement, with the smaller value associated with the greater
      regularity. Data revealed that subjects with PD had lower ApEn values than
      controls. Medication did not alter the ApEn values. These findings demonstrate
      that impaired voluntary movement in individuals with PD is associated with
      increased regularity of movement and this exaggerated regularity appears less
      sensitive to anti-PD medication. 

PMID- 24457291
TI  - An unprecedented octanuclear copper core with C(3i) symmetry and a paramagnetic
      ground state.
AB  - A complex of copper, possessing an octanuclear structure of high symmetry, has
      been prepared by a spontaneous self-assembly reaction of Cu(BF4)2 with N-tert
      butyldiethanolamine and reveals a paramagnetic ground state. 

PMID- 24457292
TI  - Sex-dependent effects of G protein-coupled estrogen receptor activity on outcome
      after ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Experimental studies indicate that estrogen typically,
      but not universally, has a neuroprotective effect in stroke. Ischemic stroke
      increases membrane-bound G protein-coupled estrogen receptor (GPER) distribution
      and expression in the brain of male but not female mice. We hypothesized that
      GPER activation may have a greater neuroprotective effect in males than in
      females after stroke. METHODS: Vehicle (dimethyl sulfoxide), a GPER agonist (G-1,
      30 MUg/kg), or a GPER antagonist (G-15, 300 MUg/kg) were administered alone or in
      combination to young or aged male mice, or young intact or ovariectomized female
      mice, 1 hour before or 3 hours after cerebral ischemia-reperfusion. Some mice
      were treated with a combination of G-1 and the pan-caspase inhibitor, quinoline
      Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh), 1 hour before stroke. We evaluated
      functional and histological end points of stroke outcome up to 72 hours after
      ischemia-reperfusion. In addition, apoptosis was examined using cleaved caspase-3
      immunohistochemistry. RESULTS: Surprisingly, G-1 worsened functional outcomes and
      increased infarct volume in males poststroke, in association with an increased
      expression of cleaved caspase-3 in peri-infarct neurons. These effects were
      blocked by G-15 or Q-VD-OPh. Conversely, G-15 improved functional outcomes and
      reduced infarct volume after stroke in males, whether given before or after
      stroke. In contrast to findings in males, G-1 reduced neurological deficit,
      apoptosis, and infarct volume in ovariectomized females, but had no significant
      effect in intact females. CONCLUSIONS: Future therapies for acute stroke could
      exploit the modulation of GPER activity in a sex-specific manner.

PMID- 24457293
TI  - De novo cerebrovascular malformation in the adult mouse after endothelial Alk1
      deletion and angiogenic stimulation.
AB  - BACKGROUND AND PURPOSE: In humans, activin receptor-like kinase 1 (Alk1)
      deficiency causes arteriovenous malformations (AVMs) in multiple organs,
      including the brain. Focal Alk1 pan-cellular deletion plus vascular endothelial
      growth factor stimulation induces brain AVMs in the adult mouse. We hypothesized
      that deletion of Alk1 in endothelial cell (EC) alone plus focal vascular
      endothelial growth factor stimulation is sufficient to induce brain AVM in the
      adult mouse. METHODS: Focal angiogenesis was induced in the brain of 8-week-old
      Pdgfb-iCreER;Alk1(2f/2f) mice by injection of adeno-associated viral vectors
      expressing vascular endothelial growth factor. Two weeks later, EC-Alk1 deletion
      was induced by tamoxifen treatment. Vascular morphology was analyzed, and EC
      proliferation and dysplasia index (number of vessels with diameter>15 MUm per 200
      vessels) were quantified 10 days after tamoxifen administration. RESULTS: Tangles
      of enlarged vessels resembling AVMs were present in the brain angiogenic region
      of tamoxifen-treated Pdgfb-iCreER;Alk1(2f/2f) mice. Induced brain AVMs were
      marked by increased dysplasia index (P<0.001) and EC proliferation clustered
      within the dysplastic vessels. AVMs were also detected around the ear tag-wound
      and in other organs. CONCLUSIONS: Deletion of Alk1 in EC in adult mice leads to
      an increased local EC proliferation during brain angiogenesis and de novo brain
      AVM.

PMID- 24457294
TI  - Association between arterial calcifications and nonlacunar and lacunar ischemic
      strokes.
AB  - BACKGROUND AND PURPOSE: Nonlacunar cerebral infarcts are presumed to be caused by
      thromboembolism from the heart or extracranial arteries, whereas lacunar infarcts
      are thought to be caused by small vessel disease. We investigated to what extent
      arterial calcifications differ between nonlacunar and lacunar ischemic strokes.
      METHODS: We studied 820 consecutive patients with transient ischemic attack or
      ischemic stroke in the anterior circulation who underwent multidetector computed
      tomography angiography and had no rare cause of stroke. The presence of likely
      cardioembolic pathogenesis was determined according to the Trial of Org 10172 in
      Acute Stroke Treatment criteria. The remaining 708 patients were categorized as
      nonlacunar or lacunar strokes, either transient ischemic attacks or strokes,
      based on clinical symptoms corrected by brain imaging results. We measured volume
      of calcifications in the aortic arch, symptomatic extracranial and intracranial
      carotid artery using multidetector computed tomography angiography. The
      difference in calcifications between nonlacunar and lacunar strokes was assessed
      with a multivariable logistic regression analysis. We adjusted for degree of
      symptomatic carotid artery stenosis and cardiovascular risk factors. RESULTS: We
      found an independent association between volume of aortic arch calcifications and
      nonlacunar ischemic strokes (adjusted odds ratio [95% confidence interval], 1.11
      [1.02-1.21]). No independent associations between extracranial and intracranial
      carotid artery calcifications and nonlacunar strokes were present. CONCLUSIONS:
      The only difference we found between nonlacunar and lacunar strokes was a higher
      calcification volume in the aortic arch in nonlacunar strokes. Our findings only
      partially confirm the notion of distinct etiologies and suggest that the
      potential role of other plaque components, plaque morphology, and aortic arch
      calcifications in ischemic stroke subtypes awaits further evaluation.

PMID- 24457295
TI  - Four decades of stroke prevention trials.

PMID- 24457297
TI  - On the character of the cyclic ionic H-bond in cryogenically cooled deprotonated
      cysteine.
AB  - The gas phase structure of deprotonated cysteine (Cys-H(+))(-) has recently
      gained attention because of its counterintuitive calculated minimum energy
      structure in which it appears that deprotonation occurs at the -SH moiety rather
      than at the nominally more acidic carboxylic acid group. Because previous
      experimental efforts have not yielded to a consensus regarding the structure of
      the anion, we report the cryogenic ion vibrational predissociation (CIVP) spectra
      of its cryogenically cooled H/D isotopologues in an effort to clarify the
      situation. The unexpected isotope dependence of key features in the spectrum and
      the similarity of the band pattern to that displayed by the intramolecular H
      bonded linkage in a deprotonated diacid (HCO2(CH2)10CO2(-)) indicate that the
      dominant form of the anion occurs with a strongly shared proton between the
      thiolate (-S(-)) and carboxylate (-CO2(-)) groups. An interesting aspect of this
      (-S(-)...H(+)...(-)O2C-) linkage is that, although the global minimum places the
      shared proton closer to the oxygen atom, the soft potential energy curve
      calculated for displacement of the bridging proton would likely support
      sufficient zero-point motion both to blur the distinction between thiolate- and
      carboxylate-based structures and to account for the unusual isotope effects.

PMID- 24457296
TI  - Risk adjustment of ischemic stroke outcomes for comparing hospital performance: a
      statement for healthcare professionals from the American Heart
      Association/American Stroke Association.
AB  - BACKGROUND AND PURPOSE: Stroke is the fourth-leading cause of death and a leading
      cause of long-term major disability in the United States. Measuring outcomes
      after stroke has important policy implications. The primary goals of this
      consensus statement are to (1) review statistical considerations when evaluating
      models that define hospital performance in providing stroke care; (2) discuss the
      benefits, limitations, and potential unintended consequences of using various
      outcome measures when evaluating the quality of ischemic stroke care at the
      hospital level; (3) summarize the evidence on the role of specific clinical and
      administrative variables, including patient preferences, in risk-adjusted models
      of ischemic stroke outcomes; (4) provide recommendations on the minimum list of
      variables that should be included in risk adjustment of ischemic stroke outcomes
      for comparisons of quality at the hospital level; and (5) provide recommendations
      for further research. METHODS AND RESULTS: This statement gives an overview of
      statistical considerations for the evaluation of hospital-level outcomes after
      stroke and provides a systematic review of the literature for the following
      outcome measures for ischemic stroke at 30 days: functional outcomes, mortality,
      and readmissions. Data on outcomes after stroke have primarily involved studies
      conducted at an individual patient level rather than a hospital level. On the
      basis of the available information, the following factors should be included in
      all hospital-level risk-adjustment models: age, sex, stroke severity, comorbid
      conditions, and vascular risk factors. Because stroke severity is the most
      important prognostic factor for individual patients and appears to be a
      significant predictor of hospital-level performance for 30-day mortality,
      inclusion of a stroke severity measure in risk-adjustment models for 30-day
      outcome measures is recommended. Risk-adjustment models that do not include
      stroke severity or other recommended variables must provide comparable
      classification of hospital performance as models that include these variables.
      Stroke severity and other variables that are included in risk-adjustment models
      should be standardized across sites, so that their reliability and accuracy are
      equivalent. There is a pressing need for research in multiple areas to better
      identify methods and metrics to evaluate outcomes of stroke care. CONCLUSIONS:
      There are a number of important methodological challenges in undertaking risk
      adjusted outcome comparisons to assess the quality of stroke care in different
      hospitals. It is important for stakeholders to recognize these challenges and for
      there to be a concerted approach to improving the methods for quality assessment
      and improvement.

PMID- 24457298
TI  - Spatio-temporal trends of nitrogen deposition and climate effects on Sphagnum
      productivity in European peatlands.
AB  - To quantify potential nitrogen (N) deposition impacts on peatland carbon (C)
      uptake, we explored temporal and spatial trends in N deposition and climate
      impacts on the production of the key peat forming functional group (Sphagnum
      mosses) across European peatlands for the period 1900-2050. Using a modelling
      approach we estimated that between 1900 and 1950 N deposition impacts remained
      limited irrespective of geographical position. Between 1950 and 2000 N deposition
      depressed production between 0 and 25% relative to 1900, particularly in
      temperate regions. Future scenarios indicate this trend will continue and become
      more pronounced with climate warming. At the European scale, the consequences for
      Sphagnum net C-uptake remained small relative to 1900 due to the low peatland
      cover in high-N areas. The predicted impacts of likely changes in N deposition on
      Sphagnum productivity appeared to be less than those of climate. Nevertheless,
      current critical loads for peatlands are likely to hold under a future climate. 

PMID- 24457299
TI  - Impact of synthetic or real urban wastewater on membrane bioreactor (MBR)
      performances and membrane fouling under stable conditions.
AB  - Influence of substrate type (synthetic (SWW) or real wastewater (RWW)) on lab
      scale MBR performances (e.g. COD and N-NH4(+) removal rates and bioactivities)
      was assessed. Membrane fouling was related to MBR biological medium
      characteristics. With RWW, autotrophic biomass was better acclimated with
      complete ammonium removal. MBR biological medium was characterized by main
      soluble microbial products (SMP) (proteins, polysaccharides and humic-like
      substances) quantification and molecular weights (MW) distribution determination.
      The biological medium of SWW acclimation contained 60mgL(-1) more of SMP, mainly
      composed of proteins and polysaccharides. A protein fraction having high MW
      (>600kDa) could be responsible for higher removable fouling fraction in that
      case. SMP of RWW experiment were mainly composed of small proteic and humic-like
      fractions, poorly retained by the membrane and resulting in a weak augmentation
      of irremovable and irreversible fouling fractions compared to SWW acclimation.
      Therefore RWW utilization is preferable to approach real operating MBR. 

PMID- 24457300
TI  - Effects of ultrasound pre-treatment on the amount of dissolved organic matter
      extracted from food waste.
AB  - This paper describes a series of studies on the effects of food waste
      disintegration using an ultrasonic generator and the production of volatile fatty
      acids (VFAs) by anaerobic hydrolysis. The results suggest that ultrasound
      treatment can significantly increase COD [chemical oxygen demand], proteins and
      reducing sugars, but decrease that of lipids in food waste supernatant.
      Ultrasound pre-treatment boosted the production of VFAs dramatically during the
      fermentation of food waste. At an ultrasonic energy density of 480W/L, we treated
      two kinds of food waste (total solids (TS): 40 and 100g/L, respectively) with
      ultrasound for 15min. The amount of COD dissolved from the waste increased by 1.6
      1.7-fold, proteins increased by 3.8-4.3-fold, and reducing sugars increased by
      4.4-3.6-fold, whereas the lipid content decreased from 2 to 0.1g/L. Additionally,
      a higher VFA yield was observed following ultrasonic pre-treatment. 

PMID- 24457301
TI  - Feasibility of spent metalworking fluids as co-substrate for anaerobic co
      digestion.
AB  - In this paper, anaerobic co-digestion of spent metalworking fluids (SMWF) and pig
      manure (PM) was evaluated. Three SMWF:PM ratios were tested in order to find the
      highest process efficiency. The best results (COD removal efficiencies of 74%)
      were achieved co-digesting a mixture with a SMWF:PM ratio of 1:99, w/w(1)
      (corresponding to 3.75mL SMWF/Lreactor week), which indicates that SMWF did not
      affect negatively PM degradation. Furthermore, two different weekly SMWF pulse
      frequencies were performed (one reactor received 1 pulse of 3.75mL/Lreactor and
      the other 3 pulses of 1.25mL/Lreactor) and no differences in COD removal
      efficiency were observed. Microbiology analysis confirmed that Pseudomonas was
      the predominant genus when treating anaerobically SMWF and the presence of a
      higher fraction of Archaea was indicative of good digester performance. This
      study confirms the feasibility of anaerobic co-digestion as an appropriate
      technology for treating and valorising SMWF. 

PMID- 24457302
TI  - A review of wet air oxidation and Thermal Hydrolysis technologies in sludge
      treatment.
AB  - With rapid world population growth and strict environmental regulations,
      increasingly large volumes of sludge are being produced in today's wastewater
      treatment plants (WWTP) with limited disposal routes. Sludge treatment has become
      an essential process in WWTP, representing 50% of operational costs. Sludge
      destruction and resource recovery technologies are therefore of great ongoing
      interest. Hydrothermal processing uses unique characteristics of water at
      elevated temperatures and pressures to deconstruct organic and inorganic
      components of sludge. It can be broadly categorized into wet oxidation
      (oxidative) and thermal hydrolysis (non-oxidative). While wet air oxidation (WAO)
      can be used for the final sludge destruction and also potentially producing
      industrially useful by-products such as acetic acid, thermal hydrolysis (TH) is
      mainly used as a pre-treatment method to improve the efficiency of anaerobic
      digestion. This paper reviews current hydrothermal technologies, roles of wet air
      oxidation and thermal hydrolysis in sludge treatment, and challenges faced by
      these technologies. 

PMID- 24457303
TI  - Potential halophilic cellulases for in situ enzymatic saccharification of ionic
      liquids pretreated lignocelluloses.
AB  - Ionic liquids (ILs) have been used as an alternative green solvent for
      lignocelluloses pretreatment. However, being a salt, ILs exhibit an inhibitory
      effect on cellulases activity, thus making the subsequent saccharification
      inefficient. The aim of the present study is to produce salt-tolerant cellulases,
      with the rationale that the enzyme also tolerant to the presence of ILs. The
      enzyme was produced from a locally isolated halophilic strain and was
      characterized and assessed for its tolerance to different types of ionic liquids.
      The results showed that halophilic cellulases produced from Aspergillus terreus
      UniMAP AA-6 exhibited higher tolerance to ILs and enhanced thermo stability in
      the presence of high saline conditions. 

PMID- 24457304
TI  - Control of nitratation in an oxygen-limited autotrophic
      nitrification/denitrification rotating biological contactor through disc
      immersion level variation.
AB  - With oxygen supply playing a crucial role in an oxygen-limited autotrophic
      nitrification/denitrification (OLAND) rotating biological contactor (RBC), its
      controlling factors were investigated in this study. Disc rotation speeds (1.8
      and 3.6rpm) showed no influence on the process performance of a lab-scale RBC,
      although abiotic experiments showed a significant effect on the oxygenation
      capacity. Estimations of the biological oxygen uptake rate revealed that 85-89%
      of the oxygen was absorbed by the microorganisms during the air exposure of the
      discs. Indeed, increasing the disc immersion (50 to 75-80%) could significantly
      suppress undesired nitratation, on the short and long term. The presented results
      demonstrated that nitratation could be controlled by the immersion level and
      revealed that oxygen control in an OLAND RBC should be predominantly based on the
      atmospheric exposure percentage of the discs. 

PMID- 24457305
TI  - Effect of nitrogen-starvation, light intensity and iron on
      triacylglyceride/carbohydrate production and fatty acid profile of Neochloris
      oleoabundans HK-129 by a two-stage process.
AB  - Triacylglyceride (TAG) and carbohydrate are potential feedstock for biofuels
      production. In this study, a two-stage process was applied for enhancing
      TAG/carbohydrate production in the selected microalgae - Neochloris oleoabundans
      HK-129. In stage I, effects of nitrogen, light intensity and iron on cell growth
      were investigated, and the highest biomass productivity of 292.83+/-5.83mg/L/d
      was achieved. In stage II, different nitrogen-starvation periods, light
      intensities and iron concentrations were employed to trigger accumulation of TAG
      and carbohydrate. The culture under 2-day N-starvation, 200MUmol/m(2)/s light
      intensity and 0.037mM Fe(3+) concentration produced the maximum TAG and
      carbohydrate productivity of 51.58mg/L/d and 90.70mg/L/d, respectively. Nitrogen
      starvation period and light intensity had marked effects on TAG/carbohydrate
      accumulation and fatty acids profile, compared to iron concentration. The
      microalgal lipid was mainly composed of C16/C18 fatty acids (90.02%), saturated
      fatty acids (29.82%), and monounsaturated fatty acids (32.67%), which is suitable
      for biodiesel synthesis. 

PMID- 24457306
TI  - Trans-membrane transport of fluoranthene by Rhodococcus sp. BAP-1 and
      optimization of uptake process.
AB  - The mechanism of transport of (14)C-fluoranthene by Rhodococcus sp. BAP-1, a Gram
      positive bacterium isolated from crude oil-polluted soil, was examined. Our
      finding demonstrated that the mechanism for fluoranthene travel across the cell
      membrane in Rhodococcus sp. BAP-1 requires energy. Meanwhile, the transport of
      fluoranthene involves concurrent catabolism of (14)C, that leading to the
      generation of significant amount of (14)CO2. Combined with trans-membrane
      transport dynamic and response surface methodology, a significant influence of
      temperature, pH and salinity on cellular uptake rate was screened by Plackett
      Burman design. Then, Box-Behnken design was employed to optimize and enhanced the
      trans-membrane transport process. The results predicted by Box-Behnken design
      indicated that the maximum cellular uptake rate of fluoranthene could be achieve
      to 0.308MUmolmin(-1)mg(-1).protein (observed) and 0.304MUmolmin(-1)mg(-1).protein
      (predicted) when the initial temperature, pH and salinity were set at 20 degrees
      C, 9% and 1%, respectively. 

PMID- 24457307
TI  - Enhanced ethanol fermentation in a pervaporation membrane bioreactor with the
      convenient permeate vapor recovery.
AB  - A continuous and closed-circulating fermentation (CCCF) system with a
      pervaporation membrane bioreactor was built for ethanol fermentation without a
      refrigeration unit to condense the permeate vapor. Two runs of experiment with a
      feature of complete and continuous coupling of fermentation and pervaporation
      were carried out, lasting for 192h and 264h, respectively. The experimental
      measurement indicated that the enhanced fermentation could be achieved with
      additional advantages of convenient permeate recovery and energy saving of the
      process. During the second experiment, the average cell concentration, glucose
      consumption rate, ethanol productivity, ethanol yield and total ethanol amount
      produced reached 19.8gL(-1), 6.06gL(-1)h(-1), 2.31gL(-1)h(-1), 0.38, and 609.8gL(
      1), respectively. During the continuous fermentation process, ethanol removal in
      situ promoted the cell second growth obviously, but the accumulation of the
      secondary metabolites in the broth became the main inhibitor against the cell
      growth and fermentation. 

PMID- 24457308
TI  - Isothermal and non-isothermal torrefaction characteristics and kinetics of
      microalga Scenedesmus obliquus CNW-N.
AB  - Isothermal and non-isothermal torrefaction characteristics and kinetics of
      microalga Scenedesmus obliquus (S. obliquus) CNW-N are studied using
      thermogravimetric analysis. The pyrolysis of S. obliquus CNW-N with increasing
      temperature is characterized by four-stage decomposition. Depending on the
      torrefaction temperature, light, mild, and severe torrefaction from the weight
      loss and the maximum decomposition rate of the microalga can be classified. Under
      the same average temperature and torrefaction duration, non-isothermal
      torrefaction gives more severe pretreatment than the isothermal one. Increasing
      the heating rate of non-isothermal torrefaction also intensifies the pretreatment
      severity. Therefore, microalgae can be torrefied via non-isothermal torrefaction
      in a shorter time under the same pretreatment extent. The atomic H/C ratio in the
      microalga decreases with increasing torrefaction severity, whereas the atomic O/C
      ratio rises. The analysis suggests that the activation energy of isothermal
      torrefaction is 57.52*10(3)Jmol(-1), while it is between 40.14*10(3) and
      88.41*10(3)Jmol(-1) for non-isothermal torrefaction. 

PMID- 24457309
TI  - Study on co-pyrolysis characteristics of rice straw and Shenfu bituminous coal
      blends in a fixed bed reactor.
AB  - Co-pyrolysis behaviors of rice straw and Shenfu bituminous coal were studied in a
      fixed bed reactor under nitrogen atmosphere. The pyrolysis temperatures were 700
      degrees C, 800 degrees C and 900 degrees C, respectively. Six different biomass
      ratios were used. Gas, tar components were analyzed by a gas chromatograph and a
      gas chromatography-mass spectrometry respectively. Under co-pyrolysis conditions,
      the gas volume yields are higher than the calculated values. Co-pyrolysis tar
      contains more phenolics, less oxygenate compounds than calculated values. The
      addition of biomass changes the atmosphere during the pyrolysis process and
      promotes tar decomposition. The SEM results show that the differences between the
      blended char and their parents char are not significant. The results of char
      yields and ultimate analysis also show that no significant interactions exist
      between the two kinds of particles. The changes of gas yield and components are
      caused by the secondary reactions and tar decomposition. 

PMID- 24457310
TI  - Synergism of cellulase, xylanase, and pectinase on hydrolyzing sugarcane bagasse
      resulting from different pretreatment technologies.
AB  - Sugarcane bagasse (SCB) resulting from different pretreatments was hydrolyzed by
      enzyme cocktails based on replacement of cellulase (Celluclast 1.5 L:Novozym
      188=1FPU:4pNPGU) by xylanase or pectinase at different proportions. Lignin
      content of NaOH pretreated SCB and hemicellulose content of H2SO4 pretreated SCB
      were the lowest. NaOH pretreatment showed the best for monosaccharide production
      among the four pretreatments. Synergism was apparently observed between cellulase
      and xylanase for monosaccharide production from steam exploded SCB (SESB), NaOH,
      and H2O2 pretreated SCB. No synergism was observed between cellulase and
      pectinase for producing glucose. Additionally, no synergism was present when
      H2SO4 pretreated SCB was used. Replacement of 20% of the cellulase by xylanase
      enhanced the glucose yield by 6.6%, 8.8%, and 9.5% from SESB, NaOH, and H2O2
      pretreated SCB, respectively. Degree of synergism between cellulase and xylanase
      had positive relationship with xylan content and was affected by hydrolysis time.

PMID- 24457311
TI  - Modeling pure culture heterotrophic production of polyhydroxybutyrate (PHB).
AB  - In this contribution a mechanistic model describing the production of
      polyhydroxybutyrate (PHB) through pure-culture fermentation was developed,
      calibrated and validated for two different substrates, namely glucose and waste
      glycerol. In both cases, non-growth-associated PHB production was triggered by
      applying nitrogen limitation. The occurrence of some growth-associated PHB
      production besides non-growth-associated PHB production was demonstrated,
      although it is inhibited in the presence of nitrogen. Other phenomena observed
      experimentally and described by the model included biomass growth on PHB and non
      linear product inhibition of PHB production. The accumulated impurities from the
      waste substrate negatively affected the obtained maximum PHB content. Overall,
      the developed mathematical model provided an accurate prediction of the dynamic
      behavior of heterotrophic biomass growth and PHB production in a two-phase pure
      culture system. 

PMID- 24457313
TI  - The effect of obesity on outcomes in mechanically ventilated patients in a
      medical intensive care unit.
AB  - BACKGROUND: The effect of obesity on outcomes in critically ill patients
      requiring invasive mechanical ventilation in a medical intensive care unit (ICU)
      is uncertain. OBJECTIVES: This study was intended to further explore the
      relationship between outcomes and obesity in patients admitted to a medical ICU
      who required invasive mechanical ventilation. METHODS: All adult patients
      admitted to the medical ICU at Washington Hospital Center requiring intubation
      and invasive mechanical ventilation for at least 24 h between January 1 and
      December 31, 2009, were retrospectively studied. Patients were categorized as
      nonobese (BMI <30) and obese (BMI >=30). The primary outcome measure was 30-day
      mortality following intubation. Secondary outcomes included ICU length of stay
      (LOS), hospital LOS and duration of mechanical ventilation. RESULTS: There were
      504 eligible patients: 306 nonobese and 198 (39%) obese. Obese patients had
      significantly higher rates of diabetes (43 vs. 30%, p = 0.004), hyperlipidemia
      (32 vs. 24%, p = 0.04), asthma (16 vs. 8%, p = 0.004) and obstructive sleep apnea
      requiring continuous positive airway pressure treatment (12 vs. 1%, p < 0.001).
      Nonobese patients had a significantly higher rate of HIV infection (10 vs. 5%, p
      = 0.05) and malignancy (21 vs. 13%, p = 0.03). There were no significant
      differences in mortality up to 30 days following intubation and secondary
      outcomes between obese and nonobese patients. Multivariate analysis using
      logistic regression showed no significant relationship between mortality rate at
      30 days following intubation and obesity. Outcomes were similar for the black
      obese (n = 153) and nonobese (n = 228) patients and the obese (n = 85) and very
      obese (n = 113) patients. CONCLUSIONS: Obesity did not influence outcomes in
      critically ill patients requiring invasive mechanical ventilation in a medical
      ICU. Black obese patients had similar outcomes to black nonobese patients, and
      very obese patients also had similar outcomes to obese patients.

PMID- 24457312
TI  - In vivo microdialysis sampling of adipokines CCL2, IL-6, and leptin in the
      mammary fat pad of adult female rats.
AB  - Adipocytes from white adipose tissue secrete cytokines and other bioactive
      proteins which are collectively termed adipokines. Adiposity has been linked with
      increased breast cancer risk as adipokines secreted by adipocytes significantly
      affect epithelial cells from which breast cancer arises. Measurement of
      extracellular adipokine concentrations that would be involved in signaling
      through mammary tissue is therefore of importance. In this work, microdialysis
      sampling was used to collect adipokines from the interstitial space of the
      mammary fat pad of female rats under isoflurane anesthesia. The adipokines CCL2
      (MCP-1), leptin and IL-6 were quantified from dialysate samples and compared to
      total tissue concentrations surrounding the implanted probes. After three hours
      of microdialysis sampling at 1 MUL min(-1), the respective median values for
      these adipokines in dialysate samples were approximately 175 pg mL(-1) (CCL2),
      150 pg mL(-1) (IL-6) and 750 pg mL(-1) (leptin). Adipokine protein levels from
      dialysates were an order of magnitude lower than levels obtained directly from
      mammary tissue. However, the adipokine concentrations between excised tissue
      surrounding the microdialysis sampling probes and control tissue without implants
      did not differ. This work demonstrates the utility of microdialysis sampling to
      quantify mammary gland adipokine levels, with relevance to understanding mammary
      physiology. 

PMID- 24457314
TI  - Design and operation of a continuous 13C and 15N labeling chamber for uniform or
      differential, metabolic and structural, plant isotope labeling.
AB  - Tracing rare stable isotopes from plant material through the ecosystem provides
      the most sensitive information about ecosystem processes; from CO2 fluxes and
      soil organic matter formation to small-scale stable-isotope biomarker probing.
      Coupling multiple stable isotopes such as (13)C with (15)N, (18)O or (2)H has the
      potential to reveal even more information about complex stoichiometric
      relationships during biogeochemical transformations. Isotope labeled plant
      material has been used in various studies of litter decomposition and soil
      organic matter formation(1-4). From these and other studies, however, it has
      become apparent that structural components of plant material behave differently
      than metabolic components (i.e. leachable low molecular weight compounds) in
      terms of microbial utilization and long-term carbon storage(5-7). The ability to
      study structural and metabolic components separately provides a powerful new tool
      for advancing the forefront of ecosystem biogeochemical studies. Here we describe
      a method for producing (13)C and (15)N labeled plant material that is either
      uniformly labeled throughout the plant or differentially labeled in structural
      and metabolic plant components. Here, we present the construction and operation
      of a continuous (13)C and (15)N labeling chamber that can be modified to meet
      various research needs. Uniformly labeled plant material is produced by
      continuous labeling from seedling to harvest, while differential labeling is
      achieved by removing the growing plants from the chamber weeks prior to harvest.
      Representative results from growing Andropogon gerardii Kaw demonstrate the
      system's ability to efficiently label plant material at the targeted levels.
      Through this method we have produced plant material with a 4.4 atom%(13)C and 6.7
      atom%(15)N uniform plant label, or material that is differentially labeled by up
      to 1.29 atom%(13)C and 0.56 atom%(15)N in its metabolic and structural components
      (hot water extractable and hot water residual components, respectively).
      Challenges lie in maintaining proper temperature, humidity, CO2 concentration,
      and light levels in an airtight (13)C-CO2 atmosphere for successful plant
      production. This chamber description represents a useful research tool to
      effectively produce uniformly or differentially multi-isotope labeled plant
      material for use in experiments on ecosystem biogeochemical cycling.

PMID- 24457315
TI  - Outcome and toxicity of stereotactic body radiotherapy with helical tomotherapy
      for inoperable lung tumor: analysis of Grade 5 radiation pneumonitis.
AB  - To analyze outcomes and toxicities of stereotactic body radiotherapy with helical
      tomotherapy (HT-SBRT) for inoperable lung tumors, the medical records of 30
      patients with 31 lung tumors treated with HT-SBRT were reviewed. The 3-year local
      control, cause-specific survival and overall survival rates (LC, CCS and OS,
      respectively) were analyzed using the Kaplan-Meier method. Toxicities were graded
      using Common Terminology Criteria for Adverse Events ver. 4. To investigate the
      factors associated with Grade 5 radiation pneumonitis (G5 RP), several parameters
      were analyzed: (i) patient-specific factors (age, gross tumor volume and PTV, and
      the interstitial pulmonary shadow on pretreatment CT); and (ii) dosimetry
      specific factors (conformity index, homogeneity index, mean lung dose, and V5,
      V10, V15, V20 and V25 of the total lungs). The median duration of observation for
      all patients was 36.5 months (range, 4-67 months). The 3-year LC, CCS and OS were
      82, 84 and 77%, respectively. Regarding Grade 3 or higher toxicities, two
      patients (6.7%) developed G5 RP. GTV was significantly associated with G5 RP (P =
      0.025), and there were non-significant but slight associations with developing G5
      RP for V5 (P = 0.067) and PTV (P = 0.096). HT-SBRT led to standard values of LC,
      CCS and OS, but also caused a markedly higher incidence of G5 RP. It is essential
      to optimize patient selection so as to avoid severe radiation pneumonitis in HT
      SBRT. 

PMID- 24457316
TI  - Pre-nucleation clusters as solute precursors in crystallisation.
AB  - Crystallisation is at the heart of various scientific disciplines, but still the
      understanding of the molecular mechanisms underlying phase separation and the
      formation of the first solid particles in aqueous solution is rather limited. In
      this review, classical nucleation theory, as well as established concepts of
      spinodal decomposition and liquid-liquid demixing, is introduced together with a
      description of the recently proposed pre-nucleation cluster pathway. The features
      of pre-nucleation clusters are presented and discussed in relation to recent
      modifications of the classical and established models for phase separation,
      together with a review of experimental work and computer simulations on the
      characteristics of pre-nucleation clusters of calcium phosphate, calcium
      carbonate, iron(oxy)(hydr)oxide, silica, and also amino acids as an example of
      small organic molecules. The role of pre-nucleation clusters as solute precursors
      in the emergence of a new phase is summarized, and the link between the chemical
      speciation of homogeneous solutions and the process of phase separation via pre
      nucleation clusters is highlighted. 

PMID- 24457317
TI  - Dysphagia following acute thalamic haemorrhage: clinical correlates and outcomes.
AB  - OBJECTIVE: A high incidence of dysphagia is seen during the acute phase of
      cerebral haemorrhage; however, there have been only rare reports of dysphagia
      caused by thalamic haemorrhage. We studied cases of thalamic haemorrhage during
      the acute period after hospitalization and examined the relationships between the
      frequency of dysphagia, stroke focus and haematoma volume. METHODS: There were
      113 subjects in this study, selected from 247 patients with thalamic haemorrhage
      who visited our rehabilitation centre. Patients were excluded if they had a
      history of dementia, stroke, confusion, epileptic seizure, surgical treatment or
      tracheotomy. We conducted a bedside swallowing assessment (BSA) by using the
      repetitive saliva swallowing test and modified water swallowing test. The
      relationships between oral intake condition at the time of hospital discharge,
      discharge destination (e.g. home), type of haematoma and haematoma volume were
      examined. RESULTS: Abnormal BSA was found in 55% of the subjects (n = 62) with
      thalamic haemorrhage. Existence of a swallowing disorder was related to haematoma
      type and haematoma volume. A regular diet was possible in 41% of the subjects (n
      = 46). Age, haematoma volume, initial BSA evaluation and cognitive function had
      the greatest influence on a subject's ability to eat a general diet at the time
      of hospital discharge. Of those subjects in whom the initial BSA evaluation was
      normal, 70% were able to eat a regular diet at discharge. However, of those in
      whom the BSA evaluation was abnormal, >70% were discharged with enteral feeding.
      Furthermore, the rates of discharge to home were 95% in patients who could eat a
      regular diet and 30% in patients who needed enteral feeding. CONCLUSIONS: In the
      acute phase of thalamic haemorrhage, dysphagia was found in a high percentage of
      subjects. Dysphagia is associated with a poor prognosis for early hospital
      discharge.

PMID- 24457318
TI  - Clinical predictors of response to EGFR tyrosine kinase inhibitors in patients
      with EGFR-mutant non-small cell lung cancer.
AB  - BACKGROUND: The presence of EGFR (epidermal growth factor receptor) mutations is
      a robust predictor of EGFR tyrosine kinase inhibitor (TKI) responsiveness.
      Predictors of EGFR-TKI responsiveness in EGFR-mutant non-small cell lung cancer
      (NSCLC) patients, however, have not been well investigated. The purpose of this
      study is to examine predictors of EGFR-TKI responsiveness in EGFR-mutant NSCLC
      patients. PATIENTS AND METHODS: Seventy EGFR-mutant NSCLC patients who received
      EGFR-TKIs in our institution between April 2007 and March 2013 were analyzed
      retrospectively. RESULTS: The objective response rate was 50.0% (95% confidence
      interval, CI, 38.6-61.4%) and the disease control rate was 91.4% (95% CI, 82.5
      96.0%). The median progression-free survival (PFS) and overall survival were 9.0
      (95% CI, 3.92-14.08) and 20.8 months (95% CI, 14.56-27.04), respectively. In
      multivariate analysis, adenocarcinoma (hazard ratio, HR, 12.25; 95% CI, 37.7
      41.10; p < 0.001) and major mutations (deletions in exon 19 and L858R point
      mutation in exon 21; HR, 2.46; 95% CI, 1.14-5.28; p = 0.022) were significant
      predictors of longer PFS. CONCLUSION: Major mutations and adenocarcinoma
      histology were independent predictors of better treatment outcome in EGFR-mutant
      NSCLC patients who received EGFR-TKIs. Further well-controlled prospective
      studies are warranted to confirm our findings.

PMID- 24457320
TI  - Cyber issue.

PMID- 24457319
TI  - Evaluation of renal function in elderly patients: performance of creatinine-based
      formulae versus the isotopic method using 99mTc-diethylene triamine pentaacetic
      acid.
AB  - INTRODUCTION: Measurement of the glomerular filtration rate (GFR) is recognized
      worldwide as the most accurate way of assessing kidney function. The prevalence
      of impaired renal function increases with advancing age. In this study we
      compared the clinical formulae Cockcroft-Gault (CG), isotope dilution mass
      spectrometry-modification of diet in renal disease (IMDS-MDRD) and chronic kidney
      disease epidemiology collaboration (CKD-EPI) with (99m)Tc-diethylene triamine
      pentaacetic acid ((99m)Tc-DTPA) in elderly patients over and under the age of 70
      years in an attempt to establish which formula produces the best measurement of
      renal function in this population. MATERIALS AND METHODS: Patients were randomly
      selected from two age groups [<70 years (n = 37) and >= 70 years (n = 39)]. Two
      plasma samples were collected at 60 and 180 min after injection of (99m)Tc-DTPA,
      and the GFR was calculated applying Charles D. Russell's two-sample method.
      RESULTS: In patients younger than 70 years, no statistically significant
      difference was found between GFR evaluated with (99m)Tc-DTPA and GFR obtained
      using the other methods.In patients aged at least 70 years, no statistically
      significant difference was found between GFR evaluated with (99m)Tc-DTPA and GFR
      evaluated using the CG real weight formula. Conversely, statistically significant
      differences were found between GFR evaluated with (99m)Tc-DTPA and GFR obtained
      using the CG normalized weight (P = 0.002), IMDS-MDRD (P = 0.024) and CKD-EPI (P
      = 0.028) formulae. DISCUSSION AND CONCLUSION: In patients older than 70 years,
      the use of the two 'classical' formulae (IMDS-MDRD and CKD-EPI) overestimated GFR
      in stage III CKD (GFR 30-59 ml/min) when compared with the gold standard (99m)Tc
      DTPA method. Thus, in patients aged 70 years and above only the CG real weight
      formula provided unbiased results comparable to (99m)Tc-DTPA. In conclusion, in
      elderly patients, GFR measured using CKD-EPI and IMDS-MDRD serum creatinine-based
      formulae may be overestimated compared with that measured using (99m)Tc-DTPA GFR.

PMID- 24457321
TI  - Introducing cyber.
AB  - In January 2012, the World Economic Forum made cyber attacks its fourth top
      global risk. In the 2013 risk report, cyber attacks were noted to be an even
      higher risk in absolute terms. The reliance of critical infrastructure on cyber
      working has never been higher; the frequency, intensity, impact and
      sophistication of attacks is growing. This trend looks likely to continue. It can
      be argued that it is no longer a question whether an organisation will be
      successfully hacked, but how long it will take to detect. In the ever-changing
      cyber environment, traditional protection techniques and reliance on preventive
      controls are not enough. A more agile approach is required to give assurance of a
      sufficiently secure digital society. Are we faced with a paradigm shift or a
      storm in a digital teacup? This paper offers an introduction to why cyber is
      important, a wider taxonomy on the topic and some historical context on how the
      discipline of cyber security has evolved, and an interpretation on what this
      means in the new normal of today. 

PMID- 24457322
TI  - Cyber security: a critical examination of information sharing versus data
      sensitivity issues for organisations at risk of cyber attack.
AB  - Cyber threats are growing and evolving at an unprecedented rate.Consequently, it
      is becoming vitally important that organisations share information internally and
      externally before, during and after incidents they encounter so that lessons can
      be learned, good practice identified and new cyber resilience capabilities
      developed. Many organisations are reluctant to share such information for fear of
      divulging sensitive information or because it may be vague or incomplete. This
      provides organisations with a complex dilemma: how to share information as openly
      as possibly about cyber incidents, while protecting their confidentiality and
      focusing on service recovery from such incidents. This paper explores the dilemma
      of information sharing versus sensitivity and provides a practical overview of
      considerations every business continuity plan should address to plan effectively
      for information sharing in the event of a cyber incident. 

PMID- 24457323
TI  - What good cyber resilience looks like.
AB  - In January 2012, the World Economic Forum made cyber attacks its fourth top
      global risk. In the 2013 risk report, cyber attacks were noted to be an even
      higher risk in absolute terms. The reliance of critical infrastructure on cyber
      working has never been higher; the frequency, intensity, impact and
      sophistication of attacks is growing. This trend looks likely to continue. It can
      be argued that it is no longer a question whether an organisation will be
      successfully hacked, but how long it will take to detect. In the ever-changing
      cyber environment, traditional protection techniques and reliance on preventive
      controls are not enough. A more agile approach is required to give assurance of a
      sufficiently secure digital society. Are we faced with a paradigm shift or a
      storm in a digital teacup? This paper offers an introduction to why cyber is
      important, a wider taxonomy on the topic and some historical context on how the
      discipline of cyber security has evolved, and an interpretation on what this
      means in the new normal of today. 

PMID- 24457324
TI  - Cyber crime: can a standard risk analysis help in the challenges facing business
      continuity managers?
AB  - Risk management has never been easy. Finding efficient mitigating measures is not
      always straightforward. Finding measures for cyber crime, however, is a really
      huge challenge because cyber threats are changing all the time. As the
      sophistication of these threats is growing, their impact increases. Moreover,
      society and its economy have become increasingly dependent on information and
      communication technologies. Standard risk analysis methodologies will help to
      score the cyber risk and to place it in the risk tolerance matrix. This will
      allow business continuity managers to figure out if there is still a gap with the
      maximum tolerable outage for time-critical business processes and if extra
      business continuity measures are necessary to fill the gap. 

PMID- 24457325
TI  - The cyber security threat stops in the boardroom.
AB  - The attitude that 'it won't happen to me' still prevails in the boardrooms of
      industry when senior executives consider the threat of targeted cyber intrusions.
      Not much has changed in the commercial world of cyber security over the past few
      years; hackers are not being challenged to find new ways to steal companies'
      intellectual property and confidential information. The consequences of even
      major security breaches seem not to be felt by the leaders of victim companies.
      Why is this so? Surely IT security practitioners are seeking new ways to detect
      and prevent targeted intrusions into companies' networks? Are the consequences of
      targeted intrusions so insignificant that the captains of industry tolerate them?
      Or do only others feel the pain of their failure? This paper initially explores
      the failure of cyber security in industry and contends that, while industry
      leaders should not be alone in accepting responsibility for this failure, they
      must take the initiative to make life harder for cyber threat actors. They cannot
      wait for government leadership on policy, strategy or coordination. The paper
      then suggests some measures that a CEO can adopt to build a new corporate
      approach to cyber security. 

PMID- 24457326
TI  - Cyber resilience: a review of critical national infrastructure and cyber security
      protection measures applied in the UK and USA.
AB  - This paper presents cyber resilience as key strand of national security. It
      establishes the importance of critical national infrastructure protection and the
      growing vicarious nature of remote, well-planned, and well executed cyber attacks
      on critical infrastructures. Examples of well-known historical cyber attacks are
      presented, and the emergence of 'internet of things' as a cyber vulnerability
      issue yet to be tackled is explored. The paper identifies key steps being
      undertaken by those responsible for detecting, deterring, and disrupting cyber
      attacks on critical national infrastructure in the United Kingdom and the USA. 

PMID- 24457327
TI  - How is cyber threat evolving and what do organisations need to consider?
AB  - Organisations and members of the public are becoming accustomed to the increasing
      velocity, frequency and variety of cyber-attacks that they have been facing over
      the last few years. In response to this challenge, it is important to explore
      what can be done to offer commercial and private users a reliable and functioning
      environment. This paper discusses how cyber threats might evolve in the future
      and seeks to explore these threats more fully. Attention is paid to the changing
      nature of cyber-attackers and their motivations and what this means for
      organisations. Finally, useful and actionable steps are provided, which
      practitioners can use to understand how they can start to address the future
      challenges of cyber security. 

PMID- 24457328
TI  - Strategies for the chemical analysis of highly porous bone scaffolds using
      secondary ion mass spectrometry.
AB  - Understanding the distribution of critical elements (e.g. silicon and calcium)
      within silica-based bone scaffolds synthesized by different methods is central to
      the optimization of these materials. Time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) has been used to determine this information due to its
      very high surface sensitivity and its ability to map all the elements and
      compounds in the periodic table with high spatial resolution. The SIMS image data
      can also be combined with depth profiles to construct three-dimensional chemical
      maps. However, the scaffolds have interconnected pore networks, which are very
      challenging structures for the SIMS technique. To overcome this problem two
      experimental methodologies have been developed. The first method involved the use
      of the focused ion beam technique to obtain clear images of the regions of
      interest and subsequently mark them by introducing fiducial marks; the samples
      were then analysed using the ToF-SIMS technique to yield the chemical analyses of
      the regions of interest. The second method involved impregnating the pores using
      a suitable reagent so that a flat surface could be achieved, and this was
      followed by secondary ion mapping and 3D chemical imaging with ToF-SIMS. The
      samples used in this work were sol-gel 70S30C foam and electrospun fibres and
      calcium-containing silica/gelatin hybrid scaffolds. The results demonstrate the
      feasibility of both these experimental methodologies and indicate that these
      methods can provide an opportunity to compare various artificial bone scaffolds,
      which will be of help in improving scaffold synthesis and processing routes. The
      techniques are also transferable to many other types of porous material. 

PMID- 24457329
TI  - A brief goal-setting and planning intervention to improve well-being for people
      with psychiatric disorders.

PMID- 24457331
TI  - Generation of a vascularized and functional human liver from an iPSC-derived
      organ bud transplant.
AB  - Generation of functional and vascularized organs from human induced pluripotent
      stem cells (iPSCs) will facilitate our understanding of human developmental
      biology and disease modeling, hopefully offering a drug-screening platform and
      providing novel therapies against end-stage organ failure. Here we describe a
      protocol for the in vitro generation of a 3D liver bud from human iPSC cultures
      and the monitoring of further hepatic maturation after transplantation at various
      ectopic sites. iPSC-derived specified hepatic cells are dissociated and suspended
      with endothelial cells and mesenchymal stem cells. These mixed cells are then
      plated onto a presolidified matrix, and they form a 3D spherical tissue mass
      termed a liver bud (iPSC-LB) in 1-2 d. To facilitate additional maturation, 4-d
      old iPSC-LBs are transplanted in the immunodeficient mouse. Live imaging has
      identified functional blood perfusion into the preformed human vascular networks.
      Functional analyses show the appearance of multiple hepatic functions in a
      chronological manner in vivo. 

PMID- 24457330
TI  - Generation and purification of highly specific antibodies for detecting post
      translationally modified proteins in vivo.
AB  - Post-translational modifications alter protein structure, affecting activity,
      stability, localization and/or binding partners. Antibodies that specifically
      recognize post-translationally modified proteins have a number of uses including
      immunocytochemistry and immunoprecipitation of the modified protein to purify
      protein-protein and protein-nucleic acid complexes. However, antibodies directed
      at modified sites on individual proteins are often nonspecific. Here we describe
      a protocol to purify polyclonal antibodies that specifically detect the modified
      protein of interest. The approach uses iterative rounds of subtraction and
      affinity purification, using stringent washes to remove antibodies that recognize
      the unmodified protein and low sequence complexity epitopes containing the
      modified amino acid. Dot blot and western blot assays are used to assess antibody
      preparation specificity. The approach is designed to overcome the common
      occurrence that a single round of subtraction and affinity purification is not
      sufficient to obtain a modified protein-specific antibody preparation. One full
      round of antibody purification and specificity testing takes 6 d of discontinuous
      time. 

PMID- 24457332
TI  - Applying thiouracil tagging to mouse transcriptome analysis.
AB  - Transcriptional profiling is a powerful approach for studying mouse development,
      physiology and disease models. Here we describe a protocol for mouse thiouracil
      tagging (TU tagging), a transcriptome analysis technology that includes in vivo
      covalent labeling, purification and analysis of cell type-specific RNA. TU
      tagging enables the isolation of RNA from a given cell population of a complex
      tissue, avoiding transcriptional changes induced by cell isolation trauma, as
      well as the identification of actively transcribed RNAs and not preexisting
      transcripts. Therefore, in contrast to other cell-specific transcriptional
      profiling methods based on the purification of tagged ribosomes or nuclei, TU
      tagging provides a direct examination of transcriptional regulation. We describe
      how to (i) deliver 4-thiouracil to transgenic mice to thio-label cell lineage
      specific transcripts, (ii) purify TU-tagged RNA and prepare libraries for
      Illumina sequencing and (iii) follow a straightforward bioinformatics workflow to
      identify cell type-enriched or differentially expressed genes. Tissue containing
      TU-tagged RNA can be obtained in 1 d, RNA-seq libraries can be generated within 2
      d and, after sequencing, an initial bioinformatics analysis can be completed in 1
      additional day. 

PMID- 24457333
TI  - Comprehensive measurement of respiratory activity in permeabilized cells using
      extracellular flux analysis.
AB  - Extracellular flux (XF) analysis has become a mainstream method for measuring
      mitochondrial function in cells and tissues. Although this technique is commonly
      used to measure bioenergetics in intact cells, we outline here a detailed XF
      protocol for measuring respiration in permeabilized cells. Cells are
      permeabilized using saponin (SAP), digitonin (DIG) or recombinant perfringolysin
      O (rPFO) (XF-plasma membrane permeabilizer (PMP) reagent), and they are provided
      with specific substrates to measure complex I- or complex II-mediated respiratory
      activity, complex III+IV respiratory activity or complex IV activity. Medium- and
      long-chain acylcarnitines or glutamine may also be provided for measuring fatty
      acid (FA) oxidation or glutamine oxidation, respectively. This protocol uses a
      minimal number of cells compared with other protocols and does not require
      isolation of mitochondria. The results are highly reproducible, and mitochondria
      remain well coupled. Collectively, this protocol provides comprehensive and
      detailed information regarding mitochondrial activity and efficiency, and, after
      preparative steps, it takes 6-8 h to complete. 

PMID- 24457334
TI  - A framework for parameter estimation and model selection from experimental data
      in systems biology using approximate Bayesian computation.
AB  - As modeling becomes a more widespread practice in the life sciences and
      biomedical sciences, researchers need reliable tools to calibrate models against
      ever more complex and detailed data. Here we present an approximate Bayesian
      computation (ABC) framework and software environment, ABC-SysBio, which is a
      Python package that runs on Linux and Mac OS X systems and that enables parameter
      estimation and model selection in the Bayesian formalism by using sequential
      Monte Carlo (SMC) approaches. We outline the underlying rationale, discuss the
      computational and practical issues and provide detailed guidance as to how the
      important tasks of parameter inference and model selection can be performed in
      practice. Unlike other available packages, ABC-SysBio is highly suited for
      investigating, in particular, the challenging problem of fitting stochastic
      models to data. In order to demonstrate the use of ABC-SysBio, in this protocol
      we postulate the existence of an imaginary reaction network composed of seven
      interrelated biological reactions (involving a specific mRNA, the protein it
      encodes and a post-translationally modified version of the protein), a network
      that is defined by two files containing 'observed' data that we provide as
      supplementary information. In the first part of the PROCEDURE, ABC-SysBio is used
      to infer the parameters of this system, whereas in the second part we use ABC
      SysBio's relevant functionality to discriminate between two different reaction
      network models, one of them being the 'true' one. Although computationally
      expensive, the additional insights gained in the Bayesian formalism more than
      make up for this cost, especially in complex problems. 

PMID- 24457335
TI  - Prehension synergies during fatigue of a single digit: adaptations in control
      with referent configurations.
AB  - The effects of muscle fatigue on the stability of precision grasps are not well
      known. The purpose of the current study was to investigate the effects of
      exercise-induced fatigue of a digit on prehension synergies in a static precision
      grasp. One group of participants performed the fatiguing exercise using the thumb
      (group-thumb) and the second group performed the exercise using the index finger
      (group-index). Grasp force and load-resisting force-stabilizing synergies were
      weaker during fatigue for group-thumb and showed no significant change for group
      index. These results indicate that fatiguing the thumb compromises the stability
      of the precision grasp more than when the index finger is fatigued. Our results
      support the idea of hierarchical organization of prehension control. We proffer
      an explanation of our results based on two control constructs: a) Principle of
      superposition. This principle states that prehension can be viewed as a
      superposition of two independent processes controlling the slip and the tilt of
      the object respectively; and b) The referent configuration hypothesis. According
      to this hypothesis, the neural control of actions is associated with defining a
      set of referent values for task-related coordinates (given an external force
      field) defined as the referent configuration. 

PMID- 24457337
TI  - Introduction of rapid methicillin-resistant Staphylococcus aureus polymerase
      chain reaction testing and antibiotic selection among hospitalized patients with
      purulent skin infections.
AB  - Introduction of a rapid methicillin-resistant Staphylococcus aureus (MRSA)
      polymerase chain reaction assay, with physician education and pharmacist
      guidance, did not significantly reduce excessive empiric prescription of MRSA
      active antibiotics despite the test's accuracy and potential to substantially
      reduce inappropriate antibiotic use.

PMID- 24457336
TI  - Expression of myeloperoxidase in acute myeloid leukemia blasts mirrors the
      distinct DNA methylation pattern involving the downregulation of DNA
      methyltransferase DNMT3B.
AB  - Myeloperoxidase (MPO) has been associated with both a myeloid lineage commitment
      and favorable prognosis in patients with acute myeloid leukemia (AML). DNA
      methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene
      promoter demethylation and MPO gene transcription in AML cells with low MPO
      activity. Therefore, MPO gene transcription was directly and indirectly regulated
      by DNA methylation. A DNA methylation microarray subsequently revealed a distinct
      methylation pattern in 33 genes, including DNA methyltransferase 3 beta (DNMT3B),
      in CD34-positive cells obtained from AML patients with a high percentage of MPO
      positive blasts. Based on the inverse relationship between the methylation status
      of DNMT3B and MPO, we found an inverse relationship between DNMT3B and MPO
      transcription levels in CD34-positive AML cells (P=0.0283). In addition, a
      distinct methylation pattern was observed in five genes related to myeloid
      differentiation or therapeutic sensitivity in CD34-positive cells from AML
      patients with a high percentage of MPO-positive blasts. Taken together, the
      results of the present study indicate that MPO may serve as an informative marker
      for identifying a distinct and crucial DNA methylation profile in CD34-positive
      AML cells.

PMID- 24457338
TI  - Editorial commentary: Measles in pregnancy is not child's play.

PMID- 24457339
TI  - Rationale for eliminating Staphylococcus breakpoints for beta-lactam agents other
      than penicillin, oxacillin or cefoxitin, and ceftaroline.
AB  - Due to the ongoing concern about the reliability of Staphylococcus breakpoints
      (interpretive criteria) for other beta-lactam agents, the Clinical and Laboratory
      Standards Institute recently approved the elimination of all breakpoints for
      antistaphylococcal beta-lactams except for penicillin, oxacillin or cefoxitin,
      and ceftaroline. Routine testing of penicillin and oxacillin or cefoxitin should
      be used to infer susceptibility for all beta-lactams with approved clinical
      indications for staphylococcal infections. It is critical for laboratories to
      reject requests for susceptibility testing of other beta-lactams against
      staphylococci and to indicate that susceptibility to these agents can be
      predicted from the penicillin and oxacillin or cefoxitin results. This article
      reviews beta-lactam resistance mechanisms in staphylococci, current antimicrobial
      susceptibility testing and reporting recommendations for beta-lactams and
      staphylococci, and microbiologic data and clinical data supporting the
      elimination of staphylococcal breakpoints for other beta-lactam agents.

PMID- 24457340
TI  - Association between short leukocyte telomere length and HIV infection in a cohort
      study: No evidence of a relationship with antiretroviral therapy.
AB  - BACKGROUND: Individuals infected with human immunodeficiency virus (HIV) appear
      to age faster than the general population, possibly related to HIV infection,
      antiretroviral therapy, and/or social/environmental factors. We evaluated
      leukocyte telomere length (LTL), a marker of cellular aging, in HIV-infected and
      uninfected adults. METHODS: Clinical data and blood were collected from Children
      and women: AntiRetrovirals and the Mechanism of Aging (CARMA) cohort study
      participants. Variables found to be important in univariate analysis were
      multivariate model candidates. RESULTS: Of the 229 HIV-infected and 166 HIV
      uninfected participants, 76% were women, and 71% were current/previous smokers.
      In a multivariate model of all participants, older age (P < .001), HIV infection
      (P = .04), active hepatitis C virus (HCV) infection (P = .02), and smoking (P <
      .003) were associated with shorter LTL. An interaction was detected, whereby
      smoking was associated with shorter LTL in HIV-uninfected subjects only. Among
      those, age and smoking (P <= .01) were related to shorter LTL. In 2 models of HIV
      infected individuals, age (P <= .002) and either active HCV infection (P = .05)
      or peak HIV RNA >=100 000 copies/mL (P = .04) were associated with shorter LTL,
      whereas other HIV disease or treatment parameters were unrelated. CONCLUSIONS:
      Our results suggest that acquisition of HIV and viral load are primarily
      responsible for the association between HIV-positive status and shorter LTL. The
      lack of association between LTL and time since HIV diagnosis, antiretroviral
      treatment, or degree of immune suppression would implicate HIV infection-related
      factors rather than disease progression or treatment. Smoking effects on LTL
      appear masked by HIV, and HCV infection may accelerate LTL shortening,
      particularly in coinfected individuals. The effect of early therapeutic
      intervention on LTL in HIV and HCV infections should be evaluated.

PMID- 24457341
TI  - Diagnostic performance of the QuantiFERON-TB Gold In-Tube assay and factors
      associated with nonpositive results in patients with miliary tuberculosis.
AB  - The QuantiFERON-TB Gold In-Tube (QFT-GIT) assay provides suboptimal diagnostic
      performance in patients with miliary tuberculosis. QFT-GIT results should be
      carefully interpreted, particularly in patients suspected of having miliary
      tuberculosis with severe lymphocytopenia or an extent of ground glass opacity
      (GGO) >50% on chest computed tomography (CT). Diagnostic performance of the QFT
      GIT assay was evaluated in 44 patients with miliary tuberculosis. Among these
      individuals, 30 (68%) had true-positive QFT-GIT results. Severe lymphocytopenia
      and an extent of GGO >50% on chest CT were independent risk factors for
      nonpositive QFT-GIT results. 

PMID- 24457343
TI  - Maternal, fetal, and neonatal outcomes associated with measles during pregnancy:
      Namibia, 2009-2010.
AB  - BACKGROUND: Previous studies of maternal, fetal, and neonatal complications of
      measles during pregnancy suggest the possibility of increased risk for morbidity
      and mortality. In 2009-2011, a nationwide laboratory-confirmed measles outbreak
      occurred in Namibia, with 38% of reported cases among adults. This outbreak
      provided an opportunity to describe clinical features of measles in pregnant
      women and assess the relative risk for adverse maternal, fetal, and neonatal
      outcomes. METHODS: A cohort of pregnant women with clinical measles was
      identified retrospectively from 6 district hospitals and clinics over a 12-month
      period. Each pregnant woman with measles was matched with 3 pregnant women
      without measles, randomly selected from antenatal clinic registers at the same
      hospital during the same time interval. We reviewed hospital and clinic records
      and conducted in-person interviews to collect demographic and clinical
      information on the pregnant women and their infants. RESULTS: Of 55 pregnant
      women with measles, 53 (96%) were hospitalized; measles-related complications
      included diarrhea (60%), pneumonia (40%), and encephalitis (5%). Among pregnant
      women with known human immunodeficiency virus (HIV) status, 15% of those without
      measles and 19% of those with measles were HIV positive. Of 42 measles-related
      pregnancies with known outcomes, 25 (60%) had >=1 adverse maternal, fetal, or
      neonatal outcome and 5 women (12%) died. Compared with 172 pregnancies without
      measles, after adjusting for age, pregnancies with measles carried significantly
      increased risks for neonatal low birth weight (adjusted relative risk [aRR] =
      3.5; 95% confidence interval [CI], 1.5-8.2), spontaneous abortion (aRR = 5.9; 95%
      CI, 1.8-19.7), intrauterine fetal death (aRR = 9.0; 95% CI, 1.2-65.5), and
      maternal death (aRR = 9.6; 95% CI, 1.3-70.0). CONCLUSIONS: Our findings suggest
      that measles virus infection during pregnancy confers a high risk of adverse
      maternal, fetal, and neonatal outcomes, including maternal death. Maximizing
      measles immunity among women of childbearing age would decrease the incidence of
      gestational measles and the attendant maternal, fetal, and neonatal morbidity and
      mortality.

PMID- 24457344
TI  - Long-term comparison of antibiotic resistance in Vibrio cholerae O1 and Shigella
      species between urban and rural Bangladesh.
AB  - From 2000 to 2012, Vibrio cholerae O1 and Shigella species isolates from urban
      Dhaka and rural Matlab were tested for resistance to all clinically relevant
      antibiotics in Bangladesh. Resistances in urban and rural Bangladesh tended to
      rise and fall together, especially a few years after the introduction of new
      resistance.

PMID- 24457346
TI  - Effect of diet on the intestinal microbiota and its activity.
AB  - PURPOSE OF REVIEW: To summarize and discuss recent findings concerning diet
      microbiota-health relations. RECENT FINDINGS: Mouse and other model animal
      studies have provided detailed insight into host-microbiota interactions, but
      cannot be extrapolated easily to humans that have different dietary habits,
      intestinal architecture, and microbiota composition. In spite of the fact that
      all humans have a personalized microbiome, the discovery of the high-level
      clusters, such as enterotypes, offer great potential for stratifying individuals
      in intervention studies based on their intestinal microbiota. A highly diverse
      microbiota seems to be key to adult human health. Long-term dietary patterns have
      been found to be associated with specific microbiota compositions and in some
      cases enterotypes. Fecal transplantations indicate that homeostasis can be
      restored and indicate that diet-microbiota-induced disorders can be improved by
      therapeutic modification of the microbiota. The specificity of complex
      carbohydrate conversion is the driving ecological force in the colon, while
      competition for sugars with the host is the driver for the small intestinal
      ecosystem. At both locations, the microbial fermentation of dietary components
      occurs in trophic chains and insight into these multispecies conversions is
      essential to understand the impact of diet on health. SUMMARY: There are clear
      associations between the microbiota, our diet and our health. However, as
      microbiota correlations with human health and diet are generally based on
      baseline comparisons between populations, there is a need for dedicated dietary
      intervention studies in humans to differentiate between correlation and
      causality.

PMID- 24457342
TI  - Long-term mortality in HIV-positive individuals virally suppressed for >3 years
      with incomplete CD4 recovery.
AB  - BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals
      initiating combination antiretroviral therapy (cART) with low CD4 counts achieve
      viral suppression but not CD4 cell recovery. We aimed to identify (1) risk
      factors for failure to achieve CD4 count >200 cells/uL after 3 years of sustained
      viral suppression and (2) the association of the achieved CD4 count with
      subsequent mortality. METHODS: We included treated HIV-infected adults from 2
      large international HIV cohorts, who had viral suppression (<=500 HIV type 1 RNA
      copies/mL) for >3 years with CD4 count <=200 cells/uL at start of the suppressed
      period. Logistic regression was used to identify risk factors for incomplete CD4
      recovery (<=200 cells/uL) and Cox regression to identify associations with
      mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4
      count >200 cells/uL after 3 years of suppression. Increasing age, lower initial
      CD4 count, male heterosexual and injection drug use transmission, cART initiation
      after 1998, and longer time from initiation of cART to start of the virally
      suppressed period were risk factors for not achieving a CD4 count >200 cells/uL.
      Individuals with CD4 <=200 cells/uL after 3 years of viral suppression had
      substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence
      interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/uL.
      The increased mortality was seen across different patient groups and for all
      causes of death. CONCLUSIONS: Virally suppressed HIV-positive individuals on cART
      who do not achieve a CD4 count >200 cells/uL have substantially increased long
      term mortality.

PMID- 24457345
TI  - Lower pill burden and once-daily antiretroviral treatment regimens for HIV
      infection: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Contemporary antiretroviral treatment regimens are simpler than in
      the past, with lower pill burden and once-daily dosing frequency common. We
      performed a meta-analysis of randomized controlled trials (RCTs) to investigate
      the impact of pill burden and once-daily vs twice-daily dosing on ART adherence
      and virological outcomes. METHODS: A literature search of 4 electronic databases
      through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART
      regimens that also reported on adherence and virological suppression were
      included. Study design, study population characteristics, intervention, outcome
      measures, and study quality were extracted. Study quality was rated using the
      Cochrane risk-of-bias tool. RESULTS: Nineteen studies met our inclusion criteria
      (N = 6312 adult patients). Higher pill burden was associated with both lower
      adherence rates (P = .004) and worse virological suppression (P < .0001) in both
      once-daily and twice-daily subgroups, although the association with adherence in
      the once-daily subgroup was not statistically significant. The average adherence
      was modestly higher in once-daily regimens than twice-daily regimens (weighted
      mean difference = 2.55%; 95% confidence interval [CI], 1.23 to 3.87; P = .0002).
      Patients on once-daily regimens did not achieve virological suppression more
      frequently than patients on twice-daily regimens (relative risk [RR] = 1.01; 95%
      CI, 0.99 to 1.03; P = .50). Both adherence and viral load suppression decreased
      over time, but adherence decreased less with once-daily dosing than with twice
      daily dosing. CONCLUSIONS: Lower pill burden was associated with both better
      adherence and virological suppression. Adherence, but not virological
      suppression, was slightly better with once- vs twice-daily regimens.

PMID- 24457347
TI  - Advances in coeliac disease.
AB  - PURPOSE OF REVIEW: To summarize the recent advances in coeliac disease. RECENT
      FINDINGS: Details of the polygenic nature of coeliac disease with the human
      leukocyte antigen (HLA) locus as the dominating genetic element have been
      uncovered. The existence of a large number of non-HLA coeliac disease genes, only
      partly shared by each individual patient, suggests the genetic heterogeneity of
      the disease. The critical role for HLA-DQ-restricted CD4 T cells recognizing
      antigenic gluten peptides is further substantiated. Involvement of CD8 T cells
      has received new attention. Other components of wheat than gluten, in particular
      the amylase trypsin inhibitors, may also play a role. The disease is becoming
      more prevalent. New guidelines state that coeliac disease diagnosis in children
      can be made on the basis of clinical signs, serology and genetics without the
      need of biopsy. The clinical entity 'noncoeliac gluten sensitivity' has received
      much attention, but diagnostic and pathophysiological definitions are still
      elusive. The risk for mortality and morbidity in coeliac disease is less than
      previously thought. SUMMARY: Our understanding of the basic and clinical aspects
      of coeliac disease increases. Coeliac disease stands out as a major health
      problem of almost global occurrence. Case finding, distinguishing coeliac disease
      from other gluten-sensitive conditions, better care and balanced use of resources
      are the current challenges.

PMID- 24457348
TI  - In situ generation of a hydroxyl radical by nanoporous activated carbon derived
      from rice husk for environmental applications: kinetic and thermodynamic
      constants.
AB  - The objective of this investigation is to evaluate the hydroxyl radical (OH)
      generation using nanoporous activated carbon (NPAC), derived from rice husk, and
      dissolved oxygen in water. The in situ production of the OH radical was confirmed
      through the DMPO spin trapping method in EPR spectroscopy and quantitative
      determination by a deoxyribose assay procedure. NPAC served as a heterogeneous
      catalyst to degrade 2-deoxy-d-ribose (a reference compound) using hydroxyl
      radical generated from dissolved oxygen in water at temperatures in the range 313
      373 K and pH 6, with first order rate constants (k = 9.2 * 10(-2) min(-1), k =
      1.2 * 10(-1) min(-1), k = 1.3 * 10(-1) min(-1) and k = 1.68 * 10(-1) min(-1)).
      The thermodynamic constants for the generation of hydroxyl radicals by NPAC and
      dissolved oxygen in water were DeltaG -1.36 kJ mol(-1) at 313 K, DeltaH 17.73 kJ
      mol(-1) and DeltaS 61.01 J mol(-1) K(-1). 

PMID- 24457349
TI  - New self-reporting questionnaire to assess urinary tract infections and
      differential diagnosis: acute cystitis symptom score.
AB  - OBJECTIVE: Development and validation of a simple and standardized self-reporting
      questionnaire for acute uncomplicated cystitis (AUC) assessing typical and
      differential symptoms, quality of life and possible changes after therapy in
      female patients with AUC. MATERIALS AND METHODS: Literature research, development
      and evaluation of the Acute Cystitis Symptom Score (ACSS), an 18-item self
      reporting questionnaire including (a) six questions about 'typical' symptoms of
      AUC, (b) four questions regarding differential diagnoses, (c) three questions on
      quality of life and (d) five questions on additional conditions which may affect
      therapy. The ACSS was evaluated in 286 women (mean age 32.3 +/- 12.3 years) in
      the Russian and Uzbek language. Measurements of reliability, validity, predictive
      ability and responsiveness were performed. RESULTS: Cronbach's alpha for the ACSS
      was 0.89, split-half reliability was 0.92 and correlation between halves was
      0.85. Mann-Whitney test revealed significant difference scores of the 'typical'
      domain between patients and controls (10.75 vs. 2.02, p < 0.001). The optimal
      threshold score was 6 points, with a 94% sensitivity and 90% specificity to
      predict AUC. The symptom score decreased significantly when comparing before and
      after therapy (10.7 vs. 2.1, p < 0.001). CONCLUSION: The new validated ACSS is
      accurate enough and can be recommended for clinical studies and practice for
      initial diagnosis and monitoring treatment of AUC. Evaluation in other languages
      is in progress.

PMID- 24457350
TI  - Auditory brainstem responses of ephrin-A2, ephrin-A5(-/-) and ephrin-A2A5(-/-)
      mice.
AB  - Eph receptors and ephrin ligands are large families of cell surface proteins
      which have established roles in axonal growth and guidance. These are well
      characterized in the visual and somatosensory systems but are less well
      documented in the auditory pathway. We examined the possible functional role of
      two ephrin genes (ephrin-A2 and ephrin-A5) in the auditory system by measuring
      auditory brainstem responses (ABR) to tone bursts from 6 to 30 kHz in ephrin-A2(
      /-), ephrin-A5(-/-) and ephrin-A2A5(-/-) (knockout) mice. At high frequencies,
      the ephrin-A2A5(-/-) mice exhibited thresholds that were significantly lower than
      in wild-type mice by approximately 20 dB, suggesting ephrin-A2 and ephrin-A5 may
      have frequency-specific effects on the auditory system. There were also
      alterations in ABR wave peak amplitudes that were specific to each mouse strain
      which suggested both peripheral and central involvement of EphA-ephrin-A
      signalling in auditory function.

PMID- 24457352
TI  - Multifarenes: new modular cavitands.
AB  - Multifarenes, a new class of macrocycles, which are constructed of alternating
      building blocks, are conveniently accessible by three complementary syntheses
      that provide modularity and scalability. In addition to metal-ion coordination,
      these cavitands show increased flexibility with increasing ring size, offering
      opportunities for induced fit to guest molecules. 

PMID- 24457351
TI  - Perception of direct gaze does not require focus of attention.
AB  - Previous research using averted (e.g., leftward or rightward) gaze indicates that
      gaze perception requires a focus of attention. However, direct gaze, compared
      with averted gaze, is processed in the brain preferentially and enhances
      cognitive functions. Thus, it is necessary to use direct gaze to investigate
      whether gaze perception is possible without focused attention. We conducted a
      dual-task paradigm in which attention was drawn away from gaze. Results showed
      performance on gaze-direction discrimination (direct vs. averted gaze) in the
      dual-task condition was only slightly lower than in the single-task condition;
      participants were able to discriminate direct from averted gaze without focusing
      their attention in a similar manner to when they did focus their attention. In
      contrast, when participants discriminated between averted gazes (leftward and
      rightward), performance dropped to near-chance levels. It was concluded that gaze
      perception does not require a focus of attention for direct gaze. 

PMID- 24457353
TI  - Genome-wide analysis of radiation-induced mutations in rice (Oryza sativa L. ssp.
      indica).
AB  - Radiation has been efficiently used for rice germplasm innovation. However, the
      molecular mechanisms by which radiation induces mutations are still unclear. In
      this study, we performed whole genome sequencing to reveal the comprehensive
      mutations in rice treated with radiation. Red-1 (a rice rich in beneficial
      ingredients for human health) was derived from rice 9311 after gamma-radiation.
      Solexa sequencing technology was applied to uncover the mutations. Compared with
      the 9311 genome, 9.19% of genome sequences were altered in the Red-1 genome.
      Among these alterations, there were 381,403 SNPs, 50,116 1-5 bp Indels, 1279 copy
      number variations, and 10,026 presence/absence variations. These alterations were
      located in 14,493 genes, the majority of which contained a kinase domain, leucine
      rich repeats, or Cyt_P450. Point mutations were the main type of variation in the
      Red-1 genome. Gene ontology clustering revealed that genes that are associated
      with cell components, binding function, catalytic activity and metabolic
      processes were susceptible to gamma-radiation. It was also predicted that 8
      mutated genes were involved in the biosynthetic pathways of beneficial products
      or pigment accumulation. We conclude that genome-wide analysis of mutations
      provides novel insights into the mechanisms by which radiation improves the
      beneficial ingredients in rice Red-1.

PMID- 24457354
TI  - Improved efficacy of endobronchial ultrasound-guided fine-needle aspiration
      biopsy in comparison to endobronchial ultrasound-guided miniforceps biopsy.
AB  - OBJECTIVE: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA)
      cytology and EBUS-miniforceps biopsy (MFB) have emerged as less invasive tools
      for evaluating mediastinal lymph nodes and pulmonary lesions. The aim of this
      study is to compare the diagnostic yields of EBUS-FNA cytology to EBUS-MFB. STUDY
      DESIGN: A retrospective cohort study was performed by reviewing the database at
      our institution between December 12, 2010, and August 10, 2012. A total of 476
      consecutive cases were identified. Of these, 227 patients had concurrent FNA and
      MFB taken during the procedure. The results and diagnostic yields of both
      techniques are calculated. RESULTS: Of the 476 cases, the mean age was 62 +/- 14
      years with 53% being males. In 453 of the total cases, the less invasive FNA
      technique alone produced enough diagnostic cytology material negating the need
      for concurrent MFB. Of these FNA cases, 280 were diagnosed as malignant
      neoplasms. The diagnostic yield of EBUS-FNA cytology was comparable to EBUS-MFB
      (95% FNA and 94% MFB). There were discordant diagnoses between cytology and
      histology in 19 of the 227 (~8.4%) cases. CONCLUSIONS: EBUS-FNA cytology is a
      more efficacious diagnostic modality compared to EBUS-MFB.

PMID- 24457355
TI  - Using neutron spin echo resolved grazing incidence scattering to investigate
      organic solar cell materials.
AB  - The spin echo resolved grazing incidence scattering (SERGIS) technique has been
      used to probe the length-scales associated with irregularly shaped crystallites.
      Neutrons are passed through two well defined regions of magnetic field; one
      before and one after the sample. The two magnetic field regions have opposite
      polarity and are tuned such that neutrons travelling through both regions,
      without being perturbed, will undergo the same number of precessions in opposing
      directions. In this case the neutron precession in the second arm is said to
      "echo" the first, and the original polarization of the beam is preserved. If the
      neutron interacts with a sample and scatters elastically the path through the
      second arm is not the same as the first and the original polarization is not
      recovered. Depolarization of the neutron beam is a highly sensitive probe at very
      small angles (<50 MUrad) but still allows a high intensity, divergent beam to be
      used. The decrease in polarization of the beam reflected from the sample as
      compared to that from the reference sample can be directly related to structure
      within the sample. In comparison to scattering observed in neutron reflection
      measurements the SERGIS signals are often weak and are unlikely to be observed if
      the in-plane structures within the sample under investigation are dilute,
      disordered, small in size and polydisperse or the neutron scattering contrast is
      low. Therefore, good results will most likely be obtained using the SERGIS
      technique if the sample being measured consist of thin films on a flat substrate
      and contain scattering features that contains a high density of moderately sized
      features (30 nm to 5 um) which scatter neutrons strongly or the features are
      arranged on a lattice. An advantage of the SERGIS technique is that it can probe
      structures in the plane of the sample. 

PMID- 24457356
TI  - Abnormal retinal thickening is a common feature among patients with ARSACS
      related phenotypes.

PMID- 24457357
TI  - Long-term outcomes of Fine Needle Diathermy for established corneal
      neovascularisation.
AB  - BACKGROUND/AIMS: Corneal neovascularisation (CoNV) can lead to significant ocular
      comorbidity with reduction in vision and cosmesis. A number of techniques have
      been described to reduce CoNV, but these can be expensive. Our study aimed to
      determine the safety, efficacy and long-term outcomes of fine needle diathermy
      (FND) for CoNV. METHODS: A 5-year retrospective study identified all cases of
      FND. Indications, intraoperative complications, and postoperative visual acuity,
      after treatment and retreatments, were documented, along with the procedure time.
      Evidence of regression and number of retreatments were identified. RESULTS: 56
      eyes from 52 patients underwent FND for CoNV. The main indications included
      herpes simplex keratitis (HSK) (53%, n=25) and microbial keratitis/peripheral
      ulcerative keratitis (13%, n=6). Pretreatment acuity was significantly correlated
      with extent of CoNV (p=0.044). One complication was noted during the procedure-an
      intrastromal and subconjunctival haemorrhage (rate 2%). 68.1% of patients
      demonstrated regression at first follow-up (mean 6.9 weeks), and 89.3% (n=42)
      showed regression with two or less treatments. Mean post-FND acuity was 0.72
      (range -0.2-3.0) vs 0.82 (-0.2-3.0) preprocedure (p=0.08). VA improved in the HSK
      subgroup (p=0.012). Mean follow-up was 18.9 months (range 1-56 months).
      CONCLUSIONS: In the largest case series reported, FND appears to be a safe and
      effective technique in the long term to induce regression of CoNV, with
      significant improvement in the VA of patients with HSK.

PMID- 24457358
TI  - Clarifying the role of ATOH7 in glaucoma endophenotypes.
AB  - BACKGROUND/AIMS: The ATOH7 gene has been previously associated with glaucoma and
      glaucoma-related traits, such as disc size and cup/disc ratio (CDR). CDR is an
      important part of the glaucoma phenotype, whereas the relationship between the
      disc size and the disease is not well understood. The aim of this study was to
      investigate whether ATOH7 is associated independently with CDR or merely with the
      size of the optic disc. METHOD: We carried out an association analysis for a
      candidate region, including ATOH7 for two populations: the Blue Mountains Eye
      Study and the TwinsUK cohort. We performed three linear regression models for (1)
      disc size adjusted on age, sex and intraocular pressure (IOP), (2) CDR adjusted
      on age, sex and IOP and (3) CDR adjusted on age, sex, IOP and disc size. RESULTS:
      A strong signal was found at rs7916697 for disc size. This single nucleotide
      polymorphism (SNP) was also associated with CDR adjusted on age, sex and IOP.
      However, this SNP was not associated with CDR when adjusted on age, sex, IOP and
      also disc size. CONCLUSIONS: This study finds that ATOH7 is associated with optic
      disc size but not independently with CDR.

PMID- 24457359
TI  - Ocular haemodynamics in patients with type 2 diabetes and coronary artery
      disease.
AB  - BACKGROUND/AIMS: To assess the relationship between ocular blood flow parameters
      and diabetic retinopathy and coronary artery disease in diabetic patients.
      METHODS: 56 patients participated in the study. Colour Doppler imaging was used
      to assess the peak systolic and end-diastolic blood velocities as well as
      resistivity index in the ophthalmic, central retinal and posterior ciliary
      arteries. The diagnosis of coronary artery disease was based on the coronary
      angiogram. RESULTS: As compared to controls, the peak systolic and end-diastolic
      blood velocities in all three evaluated vessels were significantly lower in the
      case of diabetic patients with coronary artery disease. Diabetic patients without
      coronary artery disease showed only decreased end-diastolic velocity values in
      the ophthalmic artery compared with the controls. Among diabetic patients,
      coronary artery disease was related to lower peak systolic and end-diastolic
      velocities in the central retinal artery and peak systolic velocities in the
      short posterior ciliary arteries. Diabetic retinopathy was significantly
      associated with a further decrease in end-diastolic blood velocity and an
      increase in resistivity index in the central retinal artery. CONCLUSIONS: (1)
      Flow disturbances within the ocular blood vessels of patients with type 2
      diabetes were associated with atherogenic changes of coronary arteries. (2) In
      patients with type 2 diabetes and concomitant coronary artery disease, impaired
      blood flow within the ophthalmic and short posterior ciliary arteries was not
      related to diabetic retinopathy, but diabetic retinopathy was related to
      additional blood flow impairment within the central retinal artery.

PMID- 24457360
TI  - Clinical misdiagnosis of retinoblastoma in Indian children.
AB  - AIM: To determine the rate of clinical misdiagnosis in paediatric patients who
      were enucleated for retinoblastoma and report the clinicopathological features of
      cases that were misdiagnosed. METHODS: Retrospective review of medical records of
      children who underwent a primary enucleation for advanced retinoblastoma was
      done. In all cases, the diagnosis of retinoblastoma was made on the basis of
      clinical presentation and imaging modalities. Clinicopathological features of
      eyes with discordant clinical and histopathological diagnosis were studied in
      detail. RESULTS: Of 280 eyes (280 patients) that were enucleated over a 4-year
      period, histopathological diagnosis was consistent with retinoblastoma in 276
      (98.6%) eyes. In 4 (1.4%) eyes, clinical and histopathological diagnoses were
      discordant. Histopathological features in misdiagnosed cases included one case
      each of granulomatous endophthalmitis, retinal astrocytoma, Coats' disease and
      persistent hyperplastic primary vitreous. CONCLUSIONS: To the best of our
      knowledge, this is the first study to examine the rate of clinical misdiagnosis
      of retinoblastoma from South Asia. Despite the use of modern preoperative imaging
      modalities including MRI scans, benign lesions in end-stage conditions simulated
      retinoblastoma, resulting in potentially avoidable enucleation.

PMID- 24457362
TI  - Evaluation of corneal elevation, pachymetry and keratometry in keratoconic eyes
      with respect to the stage of Amsler-Krumeich classification.
AB  - AIM: To evaluate corneal elevation, pachymetry and keratometry in keratoconic
      eyes according to the clinical stage of the disease. METHODS: This prospective
      comparative study was performed on one hundred and twenty-six eyes of 83 patients
      who had keratoconus, and 42 normal eyes of 42 age-matched subjects. Corneal
      elevation, pachymetry and keratometry were measured using a rotating Scheimpflug
      camera (Pentacam HR, Oculus) in these eyes. The area under the receiver operating
      characteristic (AUROC) curves was used to analyse the diagnostic significance of
      these parameters, with respect to each stage of Amsler-Krumeich classifications.
      AUROC was calculated to describe the predictive accuracy of the different indices
      and to determine the cut-off points where sensitivity and specificity were
      maximised. RESULTS: Posterior (0.980) and anterior (0.977) elevation differences
      showed the highest AUROCs, followed by dioptres (D) value (0.941), percentage
      thickness increase (PTI) 2 mm (0.931), PTI 4 mm (0.927), progression index
      (0.927), minimal pachymetry (0.923), average keratometry (0.914), anterior
      elevation (0.909), PTI 6 mm (0.906), posterior elevation (0.898), central
      pachymetry (0.889), PTI 8 mm (0.870), PTI 10 mm (0.864), corneal thickness
      spatial profile 2 mm (0.835) and cylinder (0.796). The differences in AUROC
      curves between anterior and posterior elevation difference measurements and other
      diagnostic parameters tended to be larger at the earlier stages of keratoconus.
      CONCLUSIONS: Anterior and posterior corneal surface height data obtained by
      enhanced ectasia display, effectively discriminates keratoconus from normal
      corneas. Elevation difference measurements may provide useful information for
      improving the diagnostic accuracy of keratoconus, especially in the early stage
      of the disease.

PMID- 24457361
TI  - Prevalence and causes of vision loss in Central and South Asia: 1990-2010.
AB  - BACKGROUND: To examine the prevalence, patterns and trends of vision impairment
      and its causes from 1990 to 2010 in Central and South Asia. METHODS: Based on the
      Global Burden of Diseases Study 2010 and ongoing literature searches, we examined
      prevalence and causes of moderate and severe vision impairment (MSVI; presenting
      visual acuity <6/18, >=3/60) and blindness (presenting visual acuity <3/60).
      RESULTS: In Central Asia, the estimated age-standardised prevalence of blindness
      decreased from 0.4% (95% CI 0.3% to 0.6%) to 0.2% (95% CI 0.2% to 0.3%) and of
      MSVI from 3.0% (95% CI 1.9% to 4.7%) to 1.9% (95% CI 1.2% to 3.2%), and in South
      Asia blindness decreased from 1.7% (95% CI 1.4% to 2.1%) to 1.1% (95% CI 0.9% to
      1.3%) and MSVI from 8.9% (95% CI 6.9% to 10.9%) to 6.4% (95% CI 5.2% to 8.2%). In
      2010, 135 000 (95% CI 99,000 to 194,000) people were blind in Central Asia and
      10,600,000 (95% CI 8,397,000 to 12,500,000) people in South Asia. MSVI was
      present in 1,178,000 (95% CI 772,000 to 2,243,000) people in the Central Asia,
      and in 71,600,000 (95% CI 57,600,000 to 92,600,000) people in South Asia. Women
      were generally more often affected than men. The leading causes of blindness
      (cataract) and MSVI (undercorrected refractive error) did not change from 1990 to
      2010. CONCLUSIONS: The prevalence of blindness and MSVI in South Asia is still
      three times higher than in Central Asia and globally, with women generally more
      often affected than women. In both regions, cataract and undercorrected
      refractive error were major causes of blindness and MSVI.

PMID- 24457363
TI  - Association between genetic polymorphisms of the prostaglandin F2alpha receptor
      gene, and response to latanoprost in patients with glaucoma and ocular
      hypertension.
AB  - AIM: To examine whether intraocular pressure (IOP) reduction by latanoprost
      correlates with single nucleotide polymorphisms (SNPs) of the prostaglandin
      F2alpha (FP) receptor gene in patients with glaucoma and ocular hypertension
      (OH). METHODS: The genotype of nine SNPs in the FP receptor gene was determined
      by direct DNA sequencing, or other techniques, in 82 patients with glaucoma or OH
      who were treated with latanoprost monotherapy in one eye. The IOP reduction was
      evaluated by the percent IOP reduction (%DeltaIOP), estimated by subtracting IOP
      fluctuations in the untreated fellow eye. Subjects were classified by %DeltaIOP
      into low responders (%DeltaIOP<10%) and others (%DeltaIOP >=10%). The correlation
      between %DeltaIOP and SNPs in the FP receptor gene was analysed. RESULTS:
      Multiple regression analysis demonstrated that the rs12093097 was the only
      significant factor that correlated with %DeltaIOP (p=0.039). Among estimated
      haplotypes, one haplotype that contained the minor allele only in rs3753380, was
      significantly correlated with low responders even after correction for multiple
      test (permutation test, p=0.037). CONCLUSIONS: An association was found between
      SNPs of the FP receptor gene and the response to latanoprost in patients with
      glaucoma or OH. The FP receptor genetic polymorphism may influence the degree of
      IOP reduction by latanoprost in these patients.

PMID- 24457364
TI  - Predictors of visual acuity and genotype-phenotype correlates in a cohort of
      patients with Stargardt disease.
AB  - PURPOSE: To assess the genotypic diversity in patients with Stargardt disease and
      to characterise epidemiological and genotypic predictors of phenotype. METHODS:
      Retrospective, cross-sectional study of 112 patients with Stargardt disease. We
      evaluated the correlation between age at presentation, best-corrected visual
      acuity (BCVA), and ABCA4 genotypes. RESULTS: Mean age at presentation was 30 +/-
      16 years (range 6-78 years) for the 112 patients of 104 families. 98 of 90
      families had a probable molecular diagnosis. We found that BCVA is not related to
      age of presentation in a linear or polynomial manner; that BCVA of patients
      presenting in the first decade was significantly worse than those presenting in
      later decades (p=0.04); that patients who harboured two or more mutations
      presented earlier and had worse BCVA than those with no or 1 mutation identified
      by any method of testing (n=112, p=3.29 * 10(-6)) or by full sequencing (n=32,
      p=0.02); that 16 patients with c.5882G>A allele demonstrated better BCVA than the
      remaining patients (p=0.01); and that 10 patients with the c.5461-10T>C mutation
      presented earlier (p=0.02 * 10(-5)) and had more severe disease. CONCLUSIONS:
      Epidemiological and genotypical findings portend visual prognosis in patients
      with Stargardt disease. Select sequence variations in ABCA4 may confer a specific
      phenotype. The present data will help in assessing patients for emerging
      therapies.

PMID- 24457365
TI  - Immunomodulatory therapy with tumour necrosis factor alpha inhibitors in children
      with antinuclear antibody-associated chronic anterior uveitis: long-term results.
AB  - AIM: The aim of the study was to assess the long-term efficacy and tolerability
      of tumour necrosis factor alpha (TNFalpha) inhibitors in the therapy of children
      with refractory antinuclear antibody (ANA)-associated chronic anterior uveitis.
      METHODS: Retrospective analysis of 31 children with ANA-associated uveitis,
      treated with TNFalpha inhibitors with a follow-up period of at least 2 years. The
      outcome measures included: control of inflammation, corticosteroid-sparing
      potential and side effects. RESULTS: Twenty-three children (74%) were treated
      with adalimumab, five children (16%) with infliximab and three children (10%)
      with etanercept. Control of uveitis, defined as 0 anterior chamber cells while on
      <=2 drops/day topical corticosteroids, was achieved in 22 of 31 patients (71%)
      after 1 year (95% CI 52% to 86%), and in 21 of 29 patients (72%) after 2 years of
      treatment (95% CI 53% to 87%). Control of uveitis was observed in 18 of 23
      children (78%) treated with adalimumab, and in two of five children (40%) treated
      with infliximab. In all children treated with etanercept, no sufficient
      inflammatory control was found. Systemic corticosteroids could be discontinued in
      71% (12/17 children) and topical corticosteroids in 55% (17/31) of the patients.
      Treatment-related side effects were found in nine children (29%, rate:
      0.10/patient-year). CONCLUSIONS: Our data show that adalimumab and infliximab
      have beneficial effects in the therapy of severe ANA-associated anterior uveitis
      in children.

PMID- 24457366
TI  - Korean patients taking alpha1-adrenergic receptor antagonists show lower
      incidence of intraoperative floppy iris syndrome than western patients.
AB  - PURPOSE: To evaluate the incidence and clinical manifestations of intraoperative
      floppy iris syndrome (IFIS) according to iris alterations in Korean patients
      taking alpha1-adrenergic receptor antagonists (alpha1-ARAs). METHODS: This is a
      prospective observational study. Two surgeons performed cataract surgery in 758
      eyes of 596 patients over a period of 12 months. Past medical history was
      reviewed, especially whether patients had been taking systemic alpha1-ARAs.
      Ultrasound biomicroscopy was performed to measure the iris thickness of the
      dilator muscle region (DMR) at half the distance between the scleral spur and the
      pupillary margin. Pupil diameter was measured and the occurrence of IFIS was
      recorded. Measurements of the alpha1-ARA group were compared with those of a
      control group matched for age and sex. RESULTS: IFIS occurred only in six eyes of
      four patients on systemic alpha1-ARA medications (0.8%). Pupil diameter in the
      alpha1-ARA medication group and the control group was not significantly
      different. The difference in mean DMR thickness in patients taking an alpha1-ARA
      and in the control group was also not statistically significant (p=0.641).
      However, within the alpha1-ARA population, the DMR thickness of IFIS cases was
      significantly lower than that of non-IFIS cases (p=0.013) CONCLUSIONS: The
      overall incidence of IFIS was far lower in Korean patients than that reported for
      western patients. IFIS patients taking alpha1-ARAs showed significantly greater
      iris DMR thinning than non-IFIS patients taking alpha1-ARAs. Our findings
      indicate that the interaction between alpha1-ARAs and melanin, which results in
      iris DMR atrophy and IFIS, is less strong in Korean patients (with dark irises)
      than western patients.

PMID- 24457367
TI  - Minimum histological safety margins in periocular basal cell carcinoma.

PMID- 24457368
TI  - Topical cyclosporine: are all indications justified?

PMID- 24457369
TI  - Different effects of intravitreally injected ranibizumab and aflibercept on
      retinal and choroidal tissues of monkey eyes.
AB  - BACKGROUND: Since there is evidence that the Fc domain of antivascular
      endothelial growth factor drugs may cause unexpected consequences in retinal and
      choroidal vessels, the effects of intravitreal ranibizumab and aflibercept on
      monkey eyes were investigated. METHODS: Four cynomolgus monkeys were
      intravitreally injected with 0.5 mg of ranibizumab and another four with 2 mg of
      aflibercept. Two untreated monkeys served as controls. Funduscopy, fluorescein
      angiography (FA), spectral-domain-optical coherence tomography (SD-OCT) and
      measurement of intraocular pressure (IOP) were performed. The eyes were inspected
      by light, fluorescence and electron microscopy. The diameter of the
      choriocapillaris (CC) was measured by morphometry, and the areas of the CC with
      free haemoglobin, CC fenestrations and endothelial thickness were quantified.
      RESULTS: Analysis showed ranibizumab permeated the retina via intercellular
      clefts, whereas aflibercept was taken up by ganglion cells, cells of the inner
      and outer retinal layers and the retinal pigment epithelium (RPE). Stasis and
      haemolysis in the choriocapillaris and choroidal vessels were more frequent after
      aflibercept treatment, which caused hypertrophy and death of individual RPE
      cells. The area of the CC was significantly reduced after both drugs compared
      with controls, but the reduction of the CC endothelium thickness, number of
      fenestrations and the areas with haemolysis were more pronounced after
      aflibercept. CONCLUSIONS: Ranibizumab permeated the retina through intercellular
      spaces, whereas aflibercept was taken up by neuronal and RPE cells. Aflibercept
      induced protein complex formation and more haemolysis in the choriocapillaris,
      leading to individual RPE cell death. The clinical significance and relation of
      these findings to the Fc domain or to other characteristics of aflibercept remain
      to be investigated.

PMID- 24457370
TI  - The evaluation and surgical management of cyclodialysis clefts that have failed
      to respond to conservative management.
AB  - PURPOSE: To investigate factors that may influence successful correction of
      hypotony in a consecutive series of patients with cyclodialysis clefts repaired
      surgically over a 10-year period. DESIGN: Retrospective interventional case
      series. METHODS: Interventional case series of consecutive patients with
      cyclodialysis clefts and hypotony treated surgically after failure of
      conservative treatment. RESULTS: Eighteen patients (18 eyes) of mean (SD) age
      48.3 (15.8) years at the time of surgery were included (16 male, 2 female). All
      were diagnosed using gonioscopy, usually assisted with intracameral viscoelastic
      injection. Imaging used in three cases was not found to be sufficiently precise
      to plan surgical intervention, without prior gonioscopic cleft visualisation. The
      intraocular pressure (IOP) was restored in nine cases (50%) after one procedure
      with a postoperative IOP (mean +/- SD) of 13.6 +/- 4.5 mm Hg (6/11 who had
      cyclopexy as a first procedure and 3/6 who had cryopexy). 2-3 procedures were
      required in the remaining nine patients. There was a trend towards the use of
      cyclopexy for larger clefts and cryopexy for smaller clefts (NS). We observed a
      trend for a lower likelihood of successful closure of larger clefts after one
      intervention. Two eyes that had cyclopexy required later IOP-lowering surgery to
      achieve IOP control. CONCLUSIONS: Most clefts were closed with one procedure. A
      trend towards larger cleft size as a preoperative risk factor for failure to
      achieve closure with one procedure was observed. In this series, imaging was not
      found to be sufficiently precise to replace viscoelastic-assisted gonioscopy in
      the diagnosis and evaluation of cyclodialysis clefts.

PMID- 24457371
TI  - Focal digital pressure for the management of posterior chamber tube shunts: a
      novel technique.

PMID- 24457372
TI  - Changes in ocular factors according to depth variation and viewer age after
      watching a three-dimensional display.
AB  - OBJECTIVE: To investigate changes in ocular factors according to the binocular
      disparity in three-dimensional (3D) images and age after watching 3D display.
      METHODS: A total of 38 volunteers were enrolled, and they watched a 3D display
      with a 1 degrees  or 3 degrees  disparity for 30 min at an interval of 1 week.
      The near point of accommodation (NPA), near point of convergence (NPC) and tear
      break-up time (tBUT) of each subject were measured before and after watching the
      3D display. In addition, the tear meniscus height and depth were measured using
      Visante optical coherence tomography and tear osmolarity was measured using
      TearLab osmometer. A survey of subjective symptoms was also conducted. RESULTS:
      NPA and NPC increased after watching the 3D display (p<0.05). NPC and NPA
      increased more in the 40s-50s group (i.e., subjects aged in their 40s and 50s)
      than in the 20s-30s group (ie, subjects aged in their 20s and 30s) after watching
      3D content with a 3 degrees  disparity (p<0.05). tBUT and tear meniscus height
      and depth decreased after watching 3D content (p<0.05). They decreased more in
      the 40s-50s group than in the 20s-30s group after watching 3D content with a 3
      degrees  disparity (p<0.05). Recovery times of NPA and NPC were significantly
      greater after watching 3D content with a 3 degrees  disparity and in the 40s-50s
      group (p<0.05). CONCLUSIONS: Watching a 3D display affects accommodation and
      convergence abilities and tear dynamics in a transient fashion, especially in the
      case of 3D images with a large binocular disparity, and in older subjects. These
      results provide helpful information for establishment of guidelines for 3D
      equipment manufacturers.

PMID- 24457373
TI  - Reactivity of mer-hydrido(2-mercaptobenzoyl)tris(trimethylphosphine)cobalt(III)
      complex.
AB  - The reactivity of mer-hydrido(2
      mercaptobenzoyl)tris(trimethylphosphine)cobalt(III) complex 1 was intensively
      studied. A series of sulfur-coordinated organocobalt complexes (2-8) were
      obtained through the reactions of 1 with RX (RX = HCl, C2H5Br and CH3I), 2
      (diphenylphosphanyl)phenol, 2-(diphenylphosphino)benzenethiol, and CO. The
      reaction of complex with ethynyltrimethylsilane under 1 bar of CO afforded a
      penta-coordinate cobalt(I) complex 11 via insertion reaction of C=C bond of
      ethynyltrimethylsilane into Co-H bond and subsequent C,C-coupling reaction
      (reductive elimination). The formation mechanism of 11 was proposed and partly
      experimentally verified. As an intermediate, the tetra-coordinate cobalt(I)
      complex 13 was isolated through the reaction of complex 1 with
      ethynyltrimethylsilane in the absence of CO. The crystal structures of complexes
      2-4, 8, and 11 were determined by X-ray diffraction.

PMID- 24457375
TI  - MicroRNA expression and functional profiles of osteosarcoma.
AB  - OBJECTIVE: Osteosarcoma (OS) is the most frequent primary malignant bone tumor in
      children and young adults. Although the introduction of combined neoadjuvant
      chemotherapy has significantly prolonged survival, the outcome for OS patients
      showing a poor response to chemotherapy is still unfavorable. In order to develop
      new therapeutic approaches, elucidation of the entire molecular pathway
      regulating OS cell proliferation would be desirable. METHODS: MicroRNA (miRNA)
      are highly conserved noncoding RNA that play important roles in the development
      and progression of various other cancers. Using miRNA microarrays capable of
      detecting a known number of 933 miRNA, 108 miRNA were found to be commonly
      expressed in 24 samples of OS tissue and subjected to a cell proliferation assay.
      RESULTS: We found that inhibition of 5 let-7 family miRNA (hsa-let-7a, b, f, g
      and i) significantly suppressed the proliferation of OS cells. Using a
      quantitative shotgun proteomics approach, we also found that the let-7 family
      miRNA regulated the expression of vimentin and serpin H1 proteins. CONCLUSIONS:
      Our present results indicate the involvement of let-7 family miRNA in regulation
      of the cell proliferation as well as epithelial-mesenchymal transition of OS.
      Thus, let-7 family miRNA may potentially provide novel targets for the
      development of therapeutic strategies against OS.

PMID- 24457374
TI  - Effects of inhibitors of the renin-angiotensin system on the efficacy of
      interferon beta-1b: a post hoc analysis of the BEYOND study.
AB  - BACKGROUND: In experimental autoimmune encephalomyelitis, inhibition of the renin
      angiotensin system with angiotensin receptor blockers (ARBs) or angiotensin
      converting enzyme (ACE) inhibitors resulted in a significantly ameliorated
      disease course. We evaluated the effects of ARBs and ACE inhibitors on the
      efficacy of interferon beta-1b in patients with relapsing-remitting multiple
      sclerosis (RRMS). METHODS: In this post hoc analysis of the BEYOND (Betaferon
      Efficacy Yielding Outcomes of a New Dose) study, clinical and MRI end points were
      compared between patients treated with interferon beta-1b 250 or 500 ug and
      concomitant ARBs or ACE inhibitors and patients treated with interferon beta-1b
      250 or 500 ug only (reference group). RESULTS: Patients in the ARB group (n = 22)
      tended to have a higher relapse rate (0.48 vs. 0.23, p = 0.051) and a higher
      number of new gadolinium-enhancing lesions (0.6 vs. 0.3, p = 0.057) than patients
      in the reference group. Patients in the ACE inhibitor group (n = 49) also tended
      to have a higher relapse rate (0.29 vs. 0.22, p = 0.357). No differences were
      observed for the other end points. CONCLUSION: In the BEYOND study cohort, a
      concomitant medication with ARBs or ACE inhibitors did not have a beneficial
      effect in patients with RRMS treated with interferon beta-1b. As patients
      appeared to have a higher relapse rate, our results warrant further
      investigation.

PMID- 24457376
TI  - Mater semper incertus est: who's your mummy?
AB  - In English law, the legal term for father has been given a broad definition but
      the definition of mother remains rooted in biology with the Roman law principle
      mater semper certa est (the mother is always certain) remaining the norm.
      However, motherhood may be acquired through giving birth to a child, by donation
      of gametes or by caring and nurturing a child so that the identity of the mother
      is no longer certain particularly in the case of surrogacy arrangements. While
      the law in the UK may automatically recognise the parental status of a
      commissioning father in a traditional surrogacy arrangement, the parental status
      of the commissioning mother is not automatically recognised in either a
      traditional or a gestational surrogacy arrangement. Thus the maxim mater est quam
      gestation demonstrat (meaning the mother is demonstrated by gestation) is also
      not approached consistently in the legal interpretation of parentage or
      motherhood in surrogacy as against other assisted reproduction methods. This
      raises questions about the extent to which motherhood should be affected by the
      method of reproduction and whether the sociological and philosophical concept of
      motherhood should, in the case of surrogacy, give rise to a new principle of
      'mater semper incertus est' (the mother is uncertain). This article will argue
      that the time has come to move away from a legal definition of 'mother' that is
      based on biology to one that recognises the different forms of motherhood. 

PMID- 24457377
TI  - Src inhibition is still a relevant target in pancreatic cancer.

PMID- 24457379
TI  - Pertuzumab and erlotinib in patients with relapsed non-small cell lung cancer: a
      phase II study using 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography imaging.
AB  - BACKGROUND: Combination blockade of human epidermal growth factor receptor (HER)
      family signaling may confer enhanced antitumor activity than single-agent
      blockade. We performed a single-arm study of pertuzumab, a monoclonal antibody
      that inhibits HER2 dimerization, and erlotinib in relapsed non-small cell lung
      cancer (NSCLC). METHODS: Patients received pertuzumab (840-mg loading dose and
      420-mg maintenance intravenously every 3 weeks) and erlotinib (150-mg or 100-mg
      dose orally, daily). The primary endpoint was response rate (RR) by 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) at day 56 in all
      patients and those with EGFR wild-type tumors. RESULTS: Of 41 patients, 28
      (68.3%) experienced treatment-related grade >=3 adverse events, including
      pneumatosis intestinalis (3 patients), resulting in early cessation of
      enrollment. Tissue samples from 32 patients showed mutated EGFR status in 9 of 41
      (22%) and wild-type EGFR in 23 of 41 (56%). The FDG-PET RR for patients with
      assessments at day 56 was 19.5% in all patients (n = 41) and 8.7% in patients
      with wild-type EGFR NSCLC (n = 23). Investigator-assessed computed tomography RR
      at day 56 was 12.2%. CONCLUSION: FDG-PET suggests that pertuzumab plus erlotinib
      is an active combination, but combination therapy was poorly tolerated, which
      limits its clinical applicability. More research is warranted to identify drug
      combinations that disrupt HER receptor signaling but that exhibit improved
      tolerability profiles.

PMID- 24457380
TI  - At the cusp of health care changes, we embrace the possibilities ahead.

PMID- 24457378
TI  - The multicenter, phase II prospective study of paclitaxel plus capecitabine as
      first-line chemotherapy in advanced gastric carcinoma.
AB  - BACKGROUND: The efficacy and toxicity of paclitaxel plus capecitabine (PX) as
      first-line treatment in advanced gastric cancer (AGC) was evaluated. METHODS:
      Patients with previously untreated AGC were included. PX was given every 3 weeks
      until a maximum of six cycles or progression. Capecitabine monotherapy was
      continued for patients without disease progression. The primary endpoint was
      progression-free survival, and secondary endpoints were objective response rate,
      overall survival (OS), and safety. RESULTS: Overall, 194 patients were treated
      per protocol and one patient was excluded because of allergy to paclitaxel.
      Response was evaluated in 175 patients, with an objective response rate of 34.8%.
      After a median follow-up of 33.2 months, disease progression was observed in 141
      patients, 137 died, and 16 were lost to follow-up, with progression-free survival
      of 188 days and OS of 354 days. In multivariate Cox regression analysis, no
      factor remained an independent predictor of OS. Forty-five patients who received
      capecitabine monotherapy after PX had longer OS (531 days). Adverse events were
      mild (Fig. 1), and the most common grade 3-4 toxicities were leucopenia and
      neutropenia. CONCLUSION: PX as a first-line treatment has promising efficacy in
      AGC. Based on these data, a phase III study has been launched for further
      investigation.

PMID- 24457381
TI  - "Get engaged" for the new year!

PMID- 24457382
TI  - Childhood obesity.

PMID- 24457383
TI  - Promoting musculoskeletal health through physical activity for all children and
      adolescents.

PMID- 24457384
TI  - Anterior cruciate ligament tears: reconstruction and rehabilitation.
AB  - Tears of the anterior cruciate ligament (ACL) are common knee injuries
      experienced by athletes and people with active lifestyles. It is important for
      members of the healthcare team to take an evidence-based approach to the
      diagnosis, surgical management, and postoperative rehabilitation of patients with
      an ACL-deficient knee. Mechanism of ACL injury and diagnostic testing is
      consistent throughout the literature. Patients frequently opt for ACL
      reconstruction, and many surgical techniques for ACL reconstruction are available
      with no clear consensus regarding superiority. Surgeon preference dictates the
      type of reconstruction and graft choice utilized. No standardized pre- and
      postoperative rehabilitation protocol exists. However, rehabilitation plays an
      important role in functional outcomes. A comprehensive rehabilitation program is
      needed pre- and postoperatively to produce positive patient outcomes. 

PMID- 24457386
TI  - Evidence-based clinical audit criteria for the prevention and management of
      delirium in the postoperative patient with a hip fracture.
AB  - Delirium is a frequent, yet often unrecognized, occurrence in elderly
      hospitalized patients. In patients with hip fracture, the incidence of delirium
      is reported to be as high as 62% and even greater if over 65 years of age. One
      approach to the prevention and management of postoperative delirium in elderly
      patients with hip fracture is the clinical audit. A clinical audit is a
      retrospective assessment of clinical care of patients and is guided by criteria
      that are evidence-based statements of best practice. The use of measurable,
      objective criterion, with an agreed standard of performance is the hallmark of an
      audit. The clinical audit criteria presented in this article for the prevention
      and management of delirium in hospitalized elderly with hip fracture were
      determined by a compilation of systematic reviews and existing evidence-based
      clinical guidelines. The following 5 audit criteria are discussed: (1) All
      elderly patients with a hip fracture are assessed for risk factors for developing
      delirium daily using a valid and reliable tool; (2) the environment of the
      patient with hip fracture is assessed daily for conduciveness to maintaining
      sensory orientation; (3) all patients with hip fracture receive essential nursing
      care; (4) appropriate clinical criteria are applied to confirm a diagnosis of
      delirium in patients with hip fracture; and (5) nonpharmacologic interventions
      are employed before pharmacologic interventions in patients with hip fracture
      with a diagnosis of delirium. 

PMID- 24457388
TI  - Diagnosis and management of gout in total knee arthroplasty.
AB  - Gout is a common arthritic condition that continues to increase in prevalence.
      Symptoms of gout include a rapid onset of pain, erythema, swelling, and warmth in
      the affected joint. These symptoms may mimic cellulitis, thrombophlebitis, and
      septic arthritis (); however, a definitive diagnosis can be obtained through
      joint aspiration and subsequent fluid analysis to assess for the presence of
      monosodium urate crystals. Gout can also be present after total joint
      replacement. Because of the similarity of symptoms to septic arthritis, the
      diagnosis may be missed. Gout may be present in a prosthetic knee or may coexist
      with septic arthritis. Therefore, analysis of knee aspirations should include
      cell count, gram stain, cultures, and an examination of the synovial fluid for
      crystals. The following case study discusses the complex issues involved in
      treating coexistent gout and infection in a prosthetic knee. 

PMID- 24457390
TI  - Total hip arthroplasty after hip fracture or osteoarthritis: are there
      differences in characteristics and outcomes in the early rehabilitative stage?
AB  - BACKGROUND: Despite some practitioner perception of an inferior outcome in
      patients with total hip arthroplasty (THA) following hip fracture (HF) vs.
      osteoarthritis (OA), few studies have analyzed this issue. PURPOSE: This cohort
      study compares characteristics and short-term outcomes in patients with THA
      following HF and OA during the rehabilitative postsurgical period. METHODS:
      Records of all consecutive patients admitted in a rehabilitation department of a
      city hospital for THA, following HF or OA, were reviewed. Outcome measures were
      the Barthel Index, passive range of motion (PROM) for hip flexion and abduction,
      and length of hospitalization in the rehabilitation department. Participants were
      assessed at admission to department and at discharge. RESULTS: Five hundred seven
      patients were included (353 in the OA group). The HF group had a longer length of
      rehabilitation hospital stay and more comorbidity, whereas the OA group had
      higher functional performances at admission. Both groups improved in all clinical
      outcome measures with less improvement in PROM abduction scores in the OA group.
      CONCLUSIONS: Patients undergoing traumatic and elective surgery have distinctive
      clinical characteristics. Results support the idea that OA patient can have a
      reduced PROM when compared with HF patients.

PMID- 24457391
TI  - Interventions for preventing falls in older people in care facilities and
      hospitals.

PMID- 24457392
TI  - Proximal tibia metaphyseal fracture with posttraumatic genu valgum deformity.

PMID- 24457395
TI  - Influence of fine-grain and solid-solution strengthening on mechanical properties
      and in vitro degradation of WE43 alloy.
AB  - As one of the most important potential candidate alloys for vascular stent
      application, Mg-Y-Zr based Mg-4.2wt%Y-2.4wt%Nd-0.6wt%Ce(La)-0.5wt%Zr (WE43)
      alloys were investigated in combination with the forming processes of micro-tubes
      with 2.0 mm diameter and 0.1 mm wall thickness. Orthogonal experimental design
      for alloy composition, vacuum melting ingot, heat treatment, integrated plastic
      deformation and micro-tube forward extrusion are included in the processing
      procedures. Significant improvements in both the mechanical properties and
      corrosion resistance in phosphate buffered saline solution for WE43 alloys were
      achieved through this processing sequence. The influence of the heat treatment
      and hot extrusion on in vitro degradation and plasticity was found to be
      associated with grain size reduction and the redistribution of intermetallic
      particles within the microstructure. As a result, the mechanical properties and
      the corrosion resistance of Mg alloys can be improved through fine-grain
      strengthening and solid-solution strengthening to some extent.

PMID- 24457397
TI  - Subclinical hypothyroidism and vascular risk: an update.
AB  - Subclinical hypothyroidism (SCH), defined as elevated serum thyroid-stimulating
      hormone (TSH) in the presence of normal circulating free thyroxine (FT4) and
      triiodothyronine (T3), is a relatively common condition. Replacement treatment
      with levothyroxine is justified only for individuals with TSH levels >10 mIU/l.
      Serum lipid levels are influenced by thyroid status and there is evidence
      pointing to a link between SCH and an unfavorable lipid profile. Despite some
      conflicting data, most studies suggest that levothyroxine treatment may exert a
      beneficial effect on the lipid profile in SCH regarding mainly total cholesterol
      and low-density lipoprotein-cholesterol. Moreover, it appears that treatment may
      also improve some other markers associated with cardiovascular (CV) disease such
      as carotid intima media thickness (cIMT) indices of endothelial function and
      other predictors of vascular risk. The complex interaction between SCH and
      predictors of vascular disease may explain the variability of the results
      obtained from studies that assessed vascular events or even changes in some
      biochemical, functional or structural variables associated with an increased risk
      of vascular events. Further investigation is warranted by means of intervention
      studies to assess the clinical significance of levothyroxine treatment in SCH
      regarding CV risk. 

PMID- 24457396
TI  - Oral glucose lowering drugs in type 2 diabetic patients with chronic kidney
      disease.
AB  - Chronic kidney disease (CKD) represents a challenge in the treatment of type 2
      diabetic patients. Renal impairment may affect drug clearance and other
      pharmacokinetic processes which can increase toxicity and drug to drug
      interactions or cause ineffective therapy. There are many oral glucose lowering
      drugs available for the treatment of type 2 diabetes mellitus (T2DM) with
      different mechanisms of action and different pharmacokinetic profiles. While all
      classes may be used in patients with mild renal impairment, therapeutic options
      for patients with moderate to severe CKD are still limited. This review focuses
      on the pharmacokinetics, metabolism, and safety of oral glucose lowering drugs in
      patients with T2DM and CKD. 

PMID- 24457398
TI  - A review of the metabolic effects of controlled-release Phentermine/Topiramate.
AB  - BACKGROUND AND OBJECTIVE: Very few drugs are approved for obesity treatment by
      regulatory agencies. Very recently phentermine/topiramate controlled-release
      [PHEN/TPM CR; (Qsymia(r))] obtained Food and Drug Administration (FDA) approval
      as an addition to a reduced-calorie diet and exercise for chronic weight
      management. Our aim was to review the available clinical evidence on weight loss,
      metabolic effects and adverse events associated with use of this product.
      METHODS: Randomized controlled trials with phentermine/topiramate controlled
      release were selected through a Medline search using the terms: phentermine and
      topiramate, phentermine and controlled release topiramate, new anti-obesity drugs
      and phentermine/topiramate, recent combinations of anti-obesity drugs and
      Qnexa(r). RESULTS: PHEN/TPM CR was associated with a weight loss of 8.1-10.9 %
      (mid and high dose, respectively), while patients in placebo groups lost 1.4-1.8
      % of their initial weight. PHEN/TPM CR also resulted in a significant decrease of
      waist circumference. Weight loss with PHEN/TPM CR was associated with a decrease
      in blood pressure but with a slight increase in the heart rate. Furthermore, in
      all trials it exerted favorable effects on lipid profile, especially on
      triglycerides and high-density lipopoprotein (HDL) cholesterol. PHEN/TPM CR
      treatment also improved insulin sensitivity and glycemia. Moreover, it decreased
      significantly progression to type 2 diabetes. In all of the studies the severe
      adverse events were similar between the control groups and the groups of PHEN/TPM
      CR. The most frequent side-effects observed in the active treatment group were
      paresthesia, dysgeusia, dry mouth, constipation and insomnia. WHAT IS NEW AND
      CONCLUSION: PHEN/TPM CR combined with lifestyle modification may be an effective
      and well-tolerated treatment for obesity and weight-related metabolic
      complications. Its long-term efficacy and safety have yet to be defined.

PMID- 24457399
TI  - The validity of current guidelines regarding surgical management of patients with
      gastric neuroendocrine neoplasms type 1: a report of a series of seven patients.
AB  - OBJECTIVE: Gastric neuroendocrine neoplasms Type 1 (GEN type 1) are mostly
      localized indolent tumors, with only a minority developing lymph node or distant
      metastasis. Although they are usually managed conservatively, large, invasive,
      recurrent and grade 2 lesions may require surgical treatment. The aim of this
      case series is to evaluate the validity of current guidelines regarding surgical
      management of patients with GEN type 1. CASES: Seven patients (5 female) with GEN
      type 1 underwent peri-gastric lymphadenectomy when at least one of the following
      criteria employed in previous guidelines was present: (i) multiple recurrent
      lesions, (ii) lesions with positive margins following endoscopic resection, (iii)
      lesions with malignant potential (deep gastric parietal wall invasion, lymph node
      enlargement, Ki67 proliferative index >2%), or (iv) presence of metastatic
      disease. Four patients met one and three two of the previously defined criteria;
      fifteen to thirty-six peri-gastric lymph nodes were resected. Following surgery
      there was no alteration in tumor staging status compared to pre-surgical staging.
      During a median follow-up of 34 months, all patients remain without any evidence
      of disease recurrence. CONCLUSION: Peri-gastric lymphadenectomy did not prove to
      be necessary for localized GEN type 1, neither for staging nor for therapeutical
      reasons. Further parameters need to be evaluated to identify the small subset of
      patients that will develop more aggressive disease.

PMID- 24457400
TI  - Thyroglossal duct cyst carcinomas: is there a need for thyroidectomy?
AB  - OBJECTIVE: Thyroglossal duct cyst (TGDC) carcinoma is a rare entity and its
      management is controversial. The aim of this retrospective study was to: (a)
      identify patients with TGDC carcinoma followed up in our clinic and (b) study
      specific characteristics of the disease and their association with thyroid
      carcinoma. DESIGN: Medical files of patients with TGDC carcinoma were reviewed
      and tumour characteristics, lymph node metastases, treatment and follow-up were
      evaluated. RESULTS: A total of 6 patients, 4 females and 2 males, mean age 39.3
      years (median 33.5), were treated for papillary thyroid carcinoma arising in a
      TGDC. Carcinoma of the thyroid gland was found simultaneously in 4 of these
      patients, while in one patient thyroid carcinoma developed 10 years after the
      diagnosis of TGDC carcinoma. A variable clinical picture and presentation was
      recorded. The most aggressive manifestation of the disease in terms of local
      infiltration, local recurrence and lymph node metastases was observed in our
      youngest patients. CONCLUSIONS: Long-term follow-up is necessary for patients
      with thyroid carcinoma arising in a TGDC. In view of the frequent co-existence of
      thyroid cancer in these patients, we would recommend detailed thyroid evaluation
      and, eventually, total thyroidectomy at initial diagnosis of TGDC carcinoma.

PMID- 24457401
TI  - Bilateral versus unilateral papillary thyroid microcarcinoma: predictive factors
      and associated histopathological findings following total thyroidectomy.
AB  - OBJECTIVE: The extent of thyroidectomy for papillary thyroid microcarcinoma
      (PTMC) is debatable. This study investigated the rate and predictive factors of
      bilateral versus unilateral PTMC with the objective of identifying those patients
      who may benefit from total thyroidectomy. DESIGN: Between January 2001 and
      December 2008, 2019 patients who underwent total thyroidectomy were examined. A
      total of 319 patients diagnosed histopathologically as PTMC were included in the
      study. The predictive value of age at diagnosis, gender, tumor size,
      multifocality, lymph node metastasis, thyroid capsule invasion and nonincidental
      diagnosis using univariate and multivariate analyses were retrospectively
      analyzed. RESULTS: Of the 319 patients with PTMC, 77 (24.1%) presented bilateral
      disease. In univariate analysis, size of tumor >=5 mm (p<0.001), multifocality
      (p<0.001), lymph node metastases (p<0.001), thyroid capsule invasion (p<0.001)
      and nonincidental diagnosis (p=0.002) were significantly associated with
      bilaterality. In multivariate analysis, tumor size (p<0.001), multifocality of
      the primary tumor in the unilateral lobe (p<0.001) and lymph node metastasis
      (p<0.001) were independent predictive factors for bilateral PTMC. CONCLUSIONS:
      Tumor size >=5 mm and multifocality of the primary carcinoma in the unilateral
      lobe were independent risk factors for bilateral PTMC. Total thyroidectomy should
      be considered for these patients, which is of importance for the prediction of
      possible recurrence of disease.

PMID- 24457402
TI  - Ten-year obesity and overweight prevalence in Greek children: a systematic review
      and meta-analysis of 2001-2010 data.
AB  - OBJECTIVE: While the US today has the highest rates worldwide of obesity, Europe,
      and particularly Southern Europe, is catching up fast. The aim of this study was
      to report the prevalence of obesity in Greek children, aged 1-12 years. DESIGN: A
      systematic review--including all studies published in English and Greek from
      January 2001 until December 2010 regarding childhood obesity, using the IOTF
      criteria--was performed. Twenty-five out of 134 published studies were finally
      selected, including 219,996 boys and 210,772 girls. RESULTS: Meta-analysis
      revealed that 10.2% (CI 95%: 9.8-10.7%) of Greek children (1-12 years) are obese,
      23.7% (CI 95%: 22.7-24.8%) are overweight and the combined prevalence of
      overweight and obesity is 34% (CI 95%: 32.7-35.3%). Subgroup analysis by gender
      showed that 11% of the boys and 9.7% of the girls were obese, while 24.1% of the
      boys and 23.2% of the girls were overweight. The combined prevalence of excess in
      body weight predominated in boys (35%), while in girls the above prevalence was
      32.7%. Cumulative analysis revealed an upward trend of the phenomenon (2001
      2003), followed by a stabilization (2003-2010). CONCLUSIONS: During the decade
      2001-2010, 1/10 Greek children was obese and 3/10 were overweight. The
      implementation of policies to reverse childhood obesity is of the utmost urgency.

PMID- 24457403
TI  - The prevalence of hypoglycemia and its impact on the quality of life (QoL) of
      type 2 diabetes mellitus patients (The HYPO Study).
AB  - OBJECTIVE: To estimate the impact of hypoglycemia on the Quality of Life (QoL)
      and its prevalence in patients with type 2 diabetes mellitus (T2DM) in Greece.
      DESIGN: A cross-sectional epidemiological study was conducted in 6631 patients
      with T2DM. QoL was assessed with the patient self-administered ADDQoL-19.
      Reliability analysis of patients' outcomes was performed to assess internal
      consistency of the ADDQoL-19. Patients were categorized according to hypoglycemia
      experience and diabetes control. Controlled patients were considered as having
      Hb1Ac <7% (53 mmol/mol) and hypoglycemic episodes were defined as laboratory
      confirmed clinical symptomatic events. RESULTS: In total, 59% of the sample had
      HbA1c >7% (53 mmol/mol) and 20.4% of patients had a history of laboratory
      confirmed hypoglycemia. The mean age was 60 years and the mean T2DM duration was
      10 years. The mean QoL score was -3.09+/-1.9 for the total sample and the mean
      score of non-hypoglycemic patients was -3.05+/-2, while the respective score of
      hypoglycemic patients was -3.26 +/-1.8, (p<=0.001). Similar results were observed
      in the group of controlled and uncontrolled patients, who scored -2.73+/-1.7 and 
      3.33+/-1.9, respectively (p<=0.001). Comparable results were identified in the
      majority of the ADDQoL-19 instrument dimensions. CONCLUSIONS: The QoL of T2DM
      patients is affected significantly by hypoglycemia and the level of disease
      control. In diabetes treatment, the ultimate goal should be optimal glycemic
      control without debilitating hypoglycemic episodes which compromise patients'
      QoL.

PMID- 24457404
TI  - Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1
      levels in women with the polycystic ovary syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by obesity and
      insulin resistance (IR), which result in elevated plasminogen activator inhibitor
      1 (PAI-1) levels. We aimed to assess the changes in PAI-1 levels in PCOS during
      treatment with metformin and during weight loss. DESIGN: Twenty-three normal
      weight women with PCOS were given metformin 850 mg bid for 6 months. Fifty
      overweight/obese women with PCOS were prescribed an energy-restricted diet, were
      instructed to exercise and were randomized to orlistat 120 mg tid or sibutramine
      10 mg qd for 6 months. RESULTS: In normal weight women, treatment with metformin
      reduced the body mass index (BMI) and circulating androgens, improved markers of
      IR and lowered PAI-1 levels. In overweight/obese women, sibutramine and orlistat
      yielded comparable reductions in BMI and markers of IR. In contrast, the effects
      on the free androgen index (FAI) differed (p=0.027): sibutramine reduced the FAI
      (p=0.005), whereas orlistat had no effect. The effects of sibutramine and
      orlistat on PAI-1 levels also differed (p=0.042): sibutramine reduced PAI-1
      levels (p<0.001), whereas orlistat had no effect. CONCLUSIONS: Metformin and
      sibutramine, but not orlistat, reduce PAI-1 levels in PCOS. The reduction in
      circulating androgens during metformin and sibutramine treatment might be
      implicated in this decline.

PMID- 24457405
TI  - Cigarette smoking has a positive and independent effect on testosterone levels.
AB  - Previous studies have suggested that testosterone levels are linked to a variety
      of diseases, such as cardiovascular disease, type-2 diabetes, the metabolic
      syndrome, erectile dysfunction, depression, stroke and osteoporosis. Since
      cigarette smoking is a major health problem and highly prevalent among men,
      several groups have studied the effects of cigarette smoking on testosterone
      levels in men. However, the results have been conflicting. Our objectives were to
      examine the association of cigarette smoking and serum levels of sex hormone
      binding globulin (SHBG), total testosterone (TT) and free testosterone (FT) in a
      large male population. Data from 2,021 men (989 nonsmokers and 1,032 smokers),
      aged 20-69, were collected from the Fangchenggang Area Male Health and
      Examination survey using an in-person interview and self-administered
      questionnaires from September to December, 2009. We have found the following: (a)
      smokers had significantly higher TT and FT levels compared to nonsmokers, even
      after stratification as per age, BMI, triglycerides and alcohol consumption. (b)
      Both TT (r = -0.083, P <0.001) and FT (r = -0.271, P <0.001) levels were
      negatively correlated to the amount of tobacco exposure. (c) Smoking was an
      independent influencing factor for the levels of both TT (unadjusted OR = 1.64,
      95% CI: 1.33-2.01, P <0.001; adjusted OR = 1.69, 95% CI: 1.34-2.13, P <0.001) and
      FT (unadjusted OR = 1.32, 95% CI: 1.08-1.61, P = 0.007; adjusted OR = 1.27, 95%
      CI: 1-1.61, P = 0.050) levels in multivariate logistic regression models before
      and after adjusting for age, BMI, fasting blood glucose, triglycerides, alcohol
      consumption and estradiol. (d) Smoking was not found to be an independent
      predictor of SHBG level after adjustment for confounders in multivariate
      regression model (P >0.05), although a positive association between increasing
      pack-years and SHBG level was observed (r = 0.174, P <0.001). More research is
      needed to elucidate the biological mechanisms and clinical significance of these
      associations. 

PMID- 24457406
TI  - Association between g.19163A>G and g.23298T>C genetic variants of the
      osteoprotegerin gene and bone mineral density in Chinese women.
AB  - OBJECTIVE: Osteoporosis is a serious and common health issue of considerable
      complexity among postmenopausal women. The osteoprotegerin gene (OPG) is
      considered to play an important role in the pathogenesis of osteoporosis. The
      objective of this study was to detect single nucleotide polymorphisms (SNPs) in
      the OPG gene and assess the association between bone mineral density (BMD) and
      SNPs in postmenopausal women. METHODS: BMD was measured at the lumbar spine (L2
      4), neck, and total hip by dual energy X-ray absorptiometry (DEXA). The
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),
      created restriction site-PCR (CRS-PCR), and DNA sequencing methods were used to
      identify the g.19163A>G and g.23298T>C polymorphisms and genotypes in 739 Chinese
      postmenopausal women. RESULTS: Our data suggest that g.19163A>G was significantly
      associated with adjusted spine BMD, neck hip BMD, and total hip BMD. Subjects
      with genotype AA had significantly higher BMD value than those of genotypes AG
      and GG (P <0.05). We failed to detect any statistically significant association
      between g.23298T>C and adjusted spine BMD and neck hip BMD, while it almost
      reached a significant association with the adjusted total hip BMD (P = 0.058).
      DISCUSSION: These findings indicate that the OPG gene is related to BMD and
      osteoporosis in Chinese postmenopausal women.

PMID- 24457407
TI  - Ectopic calcitonin secretion in a woman with large cell neuroendocrine lung
      carcinoma.
AB  - OBJECTIVE: Serum calcitonin (CT) is a sensitive but not specific marker for
      medullary thyroid carcinoma (MTC). There are a large number of conditions that
      may elevate CT levels. CASE REPORT: Herein we present the case of a 47-year old
      woman with Hashimoto thyroiditis, goiter, cervical lymphadenopathy and high CT
      and CEA levels. After surgical extirpation of the lymph node neuroendocrine
      cancer metastasis was suspected. Computed tomography of the chest showed a tumor
      mass on the right lung. Bronchoscopy was performed and pathological and
      immunohistochemical analysis revealed large cell neuroendocrine lung cancer
      (LCNEC). After chemotherapy, significant reduction of tumor mass was achieved
      with a moderate decrease in CT levels in parallel. CONCLUSIONS: We present a
      female with LCNEC, a condition which is usually observed in older men (7(th)
      decade) and is not associated with CT secretion. Hashimoto thyroiditis is
      associated with increased incidence of different types of cancers (e.g. thyroid,
      colon). No reports at present exist on the incidence of lung cancers in patients
      with thyroid disease.

PMID- 24457408
TI  - Sequential treatment with teriparatide and strontium ranelate in a postmenopausal
      woman with atypical femoral fractures after long-term bisphosphonate
      administration.
AB  - OBJECTIVE: Despite the existence of numerous case series, no evidenced-based
      medical management for atypical fractures associated with bisphosphonate (BP)
      treatment has been established. DESIGN: We report the outcome of teriparatide
      (TRP) administration followed by strontium ranelate (SR) in a woman with a
      complete and an incomplete contralateral atypical fracture of the femoral
      diaphysis (AFF) associated with BP treatment. The spontaneous complete AFF was
      managed with intramedullary nailing, discontinuation of BP and initiation TRP.
      RESULTS: Eleven months later, she suffered a contralateral incomplete AFF. At the
      completion of the TRP treatment, she had only slight discomfort in the femur with
      the incomplete AFF. BMD testing revealed increase of 7.61% at the lumbar spine
      (LS) and 0.8% at the hip. Following TRP, 1-year SR treatment resulted in further
      BMD increase of 9.2% at the LS and 1.4% in the hip, while she does not report any
      pain. Bone markers remain within the normal range. CONCLUSION: Our case indicates
      that sequential therapy with TRP and SR in cases of AFF might be a rational
      treatment option. However, there is a need for additional information concerning
      the effect of TRP and SR, given alone or sequentially, in these patients in order
      to incorporate these drugs into the management of AFF.

PMID- 24457409
TI  - Over-supplementation of vitamin D in two patients with primary
      hyperparathyroidism.
AB  - OBJECTIVE: To describe the biochemical effects of an over-supplementation of
      vitamin D3 in two patients with primary hyperparathyroidism (PHPT). DESIGN: Two
      patients (A and B) with PHPT took erroneously 2,400,000 U (300,000 U/day for 8
      days) and 4,500,000 U (300,000 U/day for 15 days) of cholecalciferol,
      respectively. They were followed for 4 months and ionized calcium, creatinine,
      PTH, 25 hydroxy-vitamin D, 1,25(OH)2D and urinary calcium/creatinine levels were
      measured. Finally, the patients were operated on and a parathyroid adenoma was
      removed in both. RESULTS: One week after the last dose of vitamin D, serum
      ionized calcium (iCa) rose from 1.35 to 1.41 mMol/L (n.r. 1.14-1.31) for patient
      A, and from 1.43 to 1.62 for patient B, while fasting urinary Calcium/Creatinine
      (uCa/Cr) augmented from 0.31 to 0.50 mg/mg, and from 0.32 to 0.55, respectively.
      During the follow-up, the average levels of iCa were 1.37 +/- 0.03 and 1.48 +/-
      0.07 mMol/L, while those of uCa/Cr were 0.29 +/- 0.13 and 0.32 +/- 0.13, both iCa
      and uCa/Cr levels returning to baseline values within 4 months. CONCLUSIONS: The
      unintentional over-supplementation of vitamin D in the two PHPT patients caused a
      moderate and temporary increase of hypercalcemia and hypercalciuria and was not
      associated with clinical signs of toxicity.

PMID- 24457410
TI  - Comment on A. Ghemigian, et al. Familial isolated primary hyperparathyroidism due
      to HRPT2 mutation.

PMID- 24457411
TI  - Eating disorder outpatients who do not respond to cognitive behavioral therapy: a
      follow-up study.

PMID- 24457413
TI  - Lung cancer: A surprising competitor.

PMID- 24457412
TI  - Airway inflammation and illness severity in response to experimental rhinovirus
      infection in asthma.
AB  - BACKGROUND: The nature of bronchial mucosal inflammation and its physiologic and
      clinical significance in rhinovirus-induced asthma exacerbations is unclear. We
      investigated bronchial mucosal inflammatory response and its association with
      physiologic and clinical outcomes in an experimental model of rhinovirus-induced
      asthma exacerbations. METHODS: We used immunohistochemistry methods to detect
      phenotypes of inflammatory cells infiltrating the bronchial mucosa before and
      after experimental rhinovirus infection in 10 subjects with asthma and 15 normal
      subjects. RESULTS: Compared with baseline, rhinovirus infection significantly
      increased the number of epithelial (P = .005) and subepithelial (P = .017)
      neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in
      both subjects with asthma (P = .009) and normal subjects (P = .018) but more so
      in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells;
      neutrophils; and eosinophils at day 4 postinfection were positively associated
      with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects
      with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P =
      .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = 
      0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023)
      and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely
      associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell
      counts were significantly associated with a greater maximum fall in FEV1 (r = 
      0.72, P = .03), whereas higher subepithelial mast cell counts were significantly
      associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P
      = .024). CONCLUSIONS: In subjects with asthma, rhinovirus infection induces
      bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration
      than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes
      during infection are related to virus load and physiologic and clinical severity,
      whereas mast cells are related to greater lung function.

PMID- 24457414
TI  - Ovarian cancer: A better mimic.

PMID- 24457415
TI  - Genomics: Seek and you shall find...

PMID- 24457418
TI  - Fluorescence-guided surgery of malignant gliomas based on 5-aminolevulinic acid:
      paradigm shifts but not a panacea.

PMID- 24457420
TI  - Improved Cerenkov counting techniques based on a free parameter model.
AB  - In the past few years, two Cerenkov methods were developed to make activity
      measurements of high-energy beta emitters in liquid scintillation counters with
      two or three photomultiplier tubes (PMTs) possible. Both methods are based on a
      free parameter model and make use of the Frank and Tamm theory for the emission
      of Cerenkov light. In this article, additional effects are discussed and further
      improvements are presented. The dependence of the refractive index of water on
      the wavelength can now be taken into account, which has also an influence on the
      upper limit of the wavelength region for the production of Cerenkov light. In
      addition, the dependence of the PMT response on the wavelength is taken into
      account. Finally, it is possible to take a potential asymmetry of efficiencies in
      a system with three PMTs into account. To this end, three free parameters are
      assigned to each individual PMT and then determined by means of a downhill
      simplex optimization algorithm. The computed counting efficiencies for a triple
      to-double coincidence ratio (TDCR) system were compared with experimental data
      for (32)P, (89)Sr, and (90)Y. 

PMID- 24457416
TI  - Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge.
AB  - We have extended our understanding of the molecular biology that underlies adult
      glioblastoma over many years. By contrast, high-grade gliomas in children and
      adolescents have remained a relatively under-investigated disease. The latest
      large-scale genomic and epigenomic profiling studies have yielded an
      unprecedented abundance of novel data and provided deeper insights into
      gliomagenesis across all age groups, which has highlighted key distinctions but
      also some commonalities. As we are on the verge of dissecting glioblastomas into
      meaningful biological subgroups, this Review summarizes the hallmark genetic
      alterations that are associated with distinct epigenetic features and patient
      characteristics in both paediatric and adult disease, and examines the complex
      interplay between the glioblastoma genome and epigenome. 

PMID- 24457419
TI  - A genome-wide metabolomic resource for tomato fruit from Solanum pennellii.
AB  - Tomato and its processed products are one of the most widely consumed fruits. Its
      domestication, however, has resulted in the loss of some 95% of the genetic and
      chemical diversity of wild relatives. In order to elucidate this diversity,
      exploit its potential for plant breeding, as well as understand its biological
      significance, analytical approaches have been developed, alongside the production
      of genetic crosses of wild relatives with commercial varieties. In this article,
      we describe a multi-platform metabolomic analysis, using NMR, mass spectrometry
      and HPLC, of introgression lines of Solanum pennellii with a domesticated line in
      order to analyse and quantify alleles (QTL) responsible for metabolic traits. We
      have identified QTL for health-related antioxidant carotenoids and tocopherols,
      as well as molecular signatures for some 2000 compounds. Correlation analyses
      have revealed intricate interactions in isoprenoid formation in the plastid that
      can be extrapolated to other crop plants. 

PMID- 24457417
TI  - Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy.
AB  - In this Timeline, we describe the characteristics of tumour antigens that are
      recognized by spontaneous T cell responses in cancer patients and the paths that
      led to their identification. We explain on what genetic basis most, but not all,
      of these antigens are tumour specific: that is, present on tumour cells but not
      on normal cells. We also discuss how strategies that target these tumour-specific
      antigens can lead either to tumour-specific or to crossreactive T cell responses,
      which is an issue that has important safety implications in immunotherapy. These
      safety issues are even more of a concern for strategies targeting antigens that
      are not known to induce spontaneous T cell responses in patients. 

PMID- 24457423
TI  - Validation of the Thai five-minute hearing test to screen hearing loss in the
      community.
AB  - BACKGROUND: Hearing impairment affects communication, social interactions, and
      quality of life. Audiometry is the gold standard method for hearing assessment.
      However, it is impractical in a country with limited resources. This study aimed
      to validate the Thai version of the Five-Minute Hearing Test (Thai-FMHT) to
      screen hearing loss in the community. METHODS: This prospective cohort study was
      conducted in Phu Wieng district, Khon Kaen Province, Thailand during July to
      September 2011. Subjects who were older than 18 years, could read or understand
      the Thai language, and wanted to participate were enrolled. Those who had
      aphasia, severe mental disability, or other conditions that precluded audiometry
      were excluded. The Thai-FMHT was first administered, followed by standard
      audiometry performed by audiologists who were blinded to the result of Thai-FMHT,
      and finally an ear examination was performed. This trial was registered with
      ClinicalTrial.gov as No. NCT01408992. RESULTS: The 558 subjects, including 176
      males (32%) and 382 females (68%), completed all of the procedures. The optimal
      cutoff point for hearing loss in this screen was 8. The sensitivity, specificity,
      and positive likelihood ratio of the Thai-FMHT to screen mild hearing loss
      (PTA0.5-2 kHz >25 dB) were 64.7% (95% CI, 56.1-72.7%), 60.0% (95% CI, 55.1
      64.7%), and 1.62 (95% CI, 1.36-1.92), respectively. Regarding screening moderate
      hearing loss (PTA0.5-2 kHz >40 dB), the sensitivity, specificity, and positive
      likelihood ratio of the Thai-FMHT were 93.1% (95% CI, 77.2-99.2%), 56.5% (95% CI,
      55.1-64.7%), and 2.1 (95% CI, 1.9-2.5), respectively. CONCLUSION: The Thai-FMHT
      has a lower cutoff point than does the original one. This test is suitable for
      use as a screening tool for hearing loss in the community.

PMID- 24457421
TI  - Improved frontoparietal white matter integrity in overweight children is
      associated with attendance at an after-school exercise program.
AB  - Aerobic fitness is associated with white matter integrity (WMI) in adults as
      measured by diffusion tensor imaging (DTI). This study examined the effect of an
      8-month exercise intervention on WMI in children. Participants were 18 sedentary,
      overweight (BMI>=85th percentile) 8- to 11-year-old children (94% Black),
      randomly assigned to either an aerobic exercise (n=10) or sedentary attention
      control group (n=8). Each group was offered an instructor-led after-school
      program every school day for approximately 8 months. Before and after the
      program, all subjects participated in DTI scans. Tractography was conducted to
      isolate the superior longitudinal fasciculus and investigate whether the exercise
      intervention affected WMI in this region. There was no group by time interaction
      for WMI in the superior longitudinal fasciculus. There was a group by time by
      attendance interaction, however, such that higher attendance at the exercise
      intervention, but not the control intervention, was associated with increased
      WMI. Heart rate and the total dose of exercise correlated with WMI changes in the
      exercise group. In the overall sample, increased WMI was associated with improved
      scores on a measure of attention and improved teacher ratings of executive
      function. This study indicates that participating in an exercise intervention
      improves WMI in children as compared to a sedentary after-school program.

PMID- 24457422
TI  - Paxillin suppresses the proliferation of HPS rat serum treated PASMCs by up
      regulating the expression of cytoskeletal proteins.
AB  - Hepatopulmonary syndrome (HPS) is a triad of advanced liver disease,
      intrapulmonary vasodilatation (IPVD), and arterial hypoxemia. The arterial
      hypoxemia induces pulmonary vascular remodelling (PVR). In recent studies, the
      role of the proliferation of pulmonary artery smooth muscle cells (PASMCs) in PVR
      associated with HPS has been established; the changes in cytoskeletal proteins
      play an essential role in the proliferation of PASMCs. Little is known about the
      relevance of cytoskeletal protein expression or the molecular mechanisms of PVR
      associated with HPS. In addition, it has been identified that paxillin could
      influence the cytoskeletal protein expression by some important signaling
      pathways in many diseases, including lung cancer and liver cancer. In this study,
      we found that HPS rat serum from a common bile duct ligation (CBDL) rat model
      decreased the expression of cytoskeletal proteins (alpha-actin, alpha-tubulin,
      and destrin) and enhanced the expression levels of paxillin mRNA and protein in
      PASMCs. After silencing paxillin with siRNA, we found that the down-regulation of
      cytoskeletal protein expression, induced by the HPS rat serum, was reversed.
      Additionally, we reported that HPS rat serum improved the proliferation of PASMCs
      and down-regulation of paxillin could significantly inhibit this variation. These
      findings suggest that the up-regulation of cytoskeletal protein expression,
      induced by the paxillin, may cause the dysregulation of PASMC proliferation as
      well as play a fundamental role in PVR associated with HPS. In conclusion, down
      regulation of paxillin by siRNA results in the inhibition of the dysregulation of
      cytoskeletal proteins and proliferation of PASMCs, suggesting a potential
      therapeutic effect on PVR associated with HPS. 

PMID- 24457424
TI  - Different types of working memory binding in epilepsy patients with unilateral
      anterior temporal lobectomy.
AB  - The medial temporal lobe is an important structure for long-term memory
      formation, but its role in working memory is less clear. Recent studies have
      shown hippocampal involvement during working memory tasks requiring binding of
      information. It is yet unclear whether this is limited to tasks containing
      spatial features. The present study contrasted three binding conditions and one
      single-item condition in patients with unilateral anterior temporal lobectomy. A
      group of 43 patients with temporal lobectomy (23 left; 20 right) and 20 matched
      controls were examined with a working memory task assessing spatial relational
      binding (object-location), non-spatial relational binding (object-object),
      conjunctive binding (object-colour) and working memory for single items. We
      varied the delay period (3 or 6s), as there is evidence showing that delay length
      may modulate working memory performance. The results indicate that performance
      was worse for patients than for controls in both relational binding conditions,
      whereas patients were unimpaired in conjunctive binding. Single-item memory was
      found to be marginally impaired, due to a deficit on long-delay trials only. In
      conclusion, working memory binding deficits are found in patients with unilateral
      anterior temporal lobectomy. The role of the medial temporal lobe in working
      memory is not limited to tasks containing spatial features. Rather, it seems to
      be involved in relational binding, but not in conjunctive binding. The medial
      temporal lobe gets involved when working memory capacity does not suffice, for
      example when relations have to be maintained or when the delay period is long. 

PMID- 24457425
TI  - Employing the plasmonic effect of the Ag-graphene composite for enhancing light
      harvesting and photoluminescence quenching efficiency of poly[2-methoxy-5-(2
      ethylhexyloxy)-1,4-phenylene-vinylene].
AB  - In this work, we report that the Ag-graphene composite (AGC) can effectively
      enhance the light harvesting and photoluminescence (PL) quenching efficiency of
      poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-vinylene] (MEH-PPV). Loading the
      AGC on MEH-PPV leads to improved light absorption ability and PL quenching
      efficiency, which is due to the strong interaction between localized surface
      plasmon resonance (LSPR)-activated Ag nanoparticles and the MEH-PPV molecule.
      Control experiment reveals that the combination of graphene and Ag nanoparticles
      achieves superior light absorptivity and PL quenching ability compared with
      individual graphene and Ag NPs. The exponential shape of the Stern-Volmer plot
      implies that both Ag and graphene in the AGC can offer the quenching pathway for
      the PL quenching process. We also found that the AGC with a broader LSPR
      absorption range is competitive in enhancing the light absorption ability and PL
      quenching efficiency of the MEH-PPV-AGC composite, because it can expand LSPR
      induced light harvesting and PL quenching response to a wider absorption range. 

PMID- 24457426
TI  - Spatial separation of molecular conformers and clusters.
AB  - Gas-phase molecular physics and physical chemistry experiments commonly use
      supersonic expansions through pulsed valves for the production of cold molecular
      beams. However, these beams often contain multiple conformers and clusters, even
      at low rotational temperatures. We present an experimental methodology that
      allows the spatial separation of these constituent parts of a molecular beam
      expansion. Using an electric deflector the beam is separated by its mass-to
      dipole moment ratio, analogous to a bender or an electric sector mass
      spectrometer spatially dispersing charged molecules on the basis of their mass-to
      charge ratio. This deflector exploits the Stark effect in an inhomogeneous
      electric field and allows the separation of individual species of polar neutral
      molecules and clusters. It furthermore allows the selection of the coldest part
      of a molecular beam, as low-energy rotational quantum states generally experience
      the largest deflection. Different structural isomers (conformers) of a species
      can be separated due to the different arrangement of functional groups, which
      leads to distinct dipole moments. These are exploited by the electrostatic
      deflector for the production of a conformationally pure sample from a molecular
      beam. Similarly, specific cluster stoichiometries can be selected, as the mass
      and dipole moment of a given cluster depends on the degree of solvation around
      the parent molecule. This allows experiments on specific cluster sizes and
      structures, enabling the systematic study of solvation of neutral molecules. 

PMID- 24457427
TI  - Mutational profiling in melanocytic tumors: multiple somatic mutations and
      clinical implications.
AB  - In this study, we analyzed multiple somatic mutations in 10 genes relevant in
      melanoma tumorigenesis and targeted therapies. Overall, 45% of the tumors showed
      mutations and, in particular, 33% had multiple mutations. Based on our results,
      we conclude that the assessment of mutation status of multiple genes, including
      CDKN2A, could provide a genetic profile that can be useful as a prognostic and
      therapeutic marker in melanocytic tumors.

PMID- 24457428
TI  - A convenient regioselective synthesis of cyclopentadienones via palladium
      catalyzed [2+2+1] cyclocarbonylation of alkynes.
AB  - A simple and efficient synthesis of cyclopentadienones via palladium-catalyzed
      cyclocarbonylation of alkynes under atmospheric pressure of carbon monoxide has
      been developed. The transformation was carried out under mild and ligand-free
      conditions, a wide range of substrates and exceptional functional group
      tolerance. 

PMID- 24457429
TI  - The biocompatibility of silk fibroin and acellular collagen scaffolds for tissue
      engineering in the ear.
AB  - Recent experimental studies have shown the suitability of silk fibroin scaffold
      (SFS) and porcine-derived acellular collagen I/III scaffold (ACS) as onlay graft
      materials for tympanic membrane perforation repair. The aims of this study were
      to further characterize and evaluate the in vivo biocompatibility of SFS and ACS
      compared with commonly used materials such as Gelfoam and paper in a rat model.
      The scaffolds were implanted in subcutaneous (SC) tissue and middle ear (ME)
      cavity followed by histological and otoscopic evaluation for up to 26 weeks. Our
      results revealed that SFS and ACS were well tolerated and compatible in rat SC
      and ME tissues throughout the study. The tissue response adjacent to the implants
      evaluated by histology and otoscopy showed SFS and ACS to have a milder tissue
      response with minimal inflammation compared to that of paper. Gelfoam gave
      similar results to SFS and ACS after SC implantation, but it was found to be
      associated with pronounced fibrosis and osteoneogenesis after ME implantation. It
      is concluded that SFS and ACS both were biocompatible and could serve as
      potential alternative scaffolds for tissue engineering in the ear.

PMID- 24457431
TI  - Breast cancer genetics: the past, present and future.

PMID- 24457430
TI  - Protein-like fully reversible tetramerisation and super-association of an
      aminocellulose.
AB  - Unusual protein-like, partially reversible associative behaviour has recently
      been observed in solutions of the water soluble carbohydrates known as 6-deoxy-6
      (omega-aminoalkyl)aminocelluloses, which produce controllable self-assembling
      films for enzyme immobilisation and other biotechnological applications. Now, for
      the first time, we have found a fully reversible self-association
      (tetramerisation) within this family of polysaccharides. Remarkably these
      carbohydrate tetramers are then seen to associate further in a regular way into
      supra-molecular complexes. Fully reversible oligomerisation has been hitherto
      completely unknown for carbohydrates and instead resembles in some respects the
      assembly of polypeptides and proteins like haemoglobin and its sickle cell
      mutation. Our traditional perceptions as to what might be considered "protein
      like" and what might be considered as "carbohydrate-like" behaviour may need to
      be rendered more flexible, at least as far as interaction phenomena are
      concerned. 

PMID- 24457432
TI  - High-sensitivity troponin after running--a systematic review.
AB  - A systematic review was carried out to study the pattern of high-sensitivity
      cardiac troponin release after running (search performed on PubMed, ISI Web of
      Knowledge and Scopus databases). A total of ten reports were identified as
      meeting the pre-specified criteria (eight using high-sensitivity troponin T and
      two using high-sensitivity troponin I). The papers were published between 2009
      and 2013, amounting to a total of 479 participants under study. Eight reports
      provided data comparing post-running troponin levels with the 99th percentile
      reference value. A total number of 296 participants, out of 424, showed post
      running high-sensitivity troponin values higher than the 99th percentile
      reference value (69.8%). In conclusion, using high-sensitivity cardiac troponin
      assays, studies have shown that elevated post-running values are seen in more
      than two-thirds of runners. Whether troponin release in this setting represents a
      fully reversible phenomenon is currently unknown; the effects of strenuous
      running on long-term health are also uncertain. 

PMID- 24457433
TI  - CAS P8 -652 6N del polymorphism and breast cancer risk: a systematic review and
      meta-analysis.
AB  - PURPOSE: Many studies have investigated the association between CASP8-652 6N del
      polymorphism and the risk of breast cancer, but the result is still unclear owing
      to the obvious inconsistence among those studies. This study aims to quantify the
      strength of association between CASP8-652 6N del polymorphism and risk of breast
      cancer. METHODS: We searched the electronic MEDLINE database for studies relating
      to the association between CASP8-652 6N del polymorphism and risk of breast
      cancer. We estimated summary odds ratios (ORs) with their 95% confidence
      intervals (95% CIs) to assess the association. Ten case-control studies with
      13,220 cases and 13,750 controls were included into this meta-analysis. RESULTS:
      Meta-analysis of a total of ten studies showed that reduced breast cancer risk
      was associated with CASP8 -652 6N del polymorphism (homozygous: OR=0.85, 95% CI
      0.93-0.98). After adjustment for heterogeneity, meta-analysis showed that reduced
      breast cancer risk was also associated with CASP8-652 6N del polymorphism
      (homozygous: OR=0.78, 95% CI 0.63-0.95, dominant: OR=0.93, 95% CI 0.88-0.99). For
      Caucasians, CASP8-652 6N del was associated with reduced breast cancer risk at a
      borderline level (homozygous: OR=0.94, 95% CI 0.86-1.02, heterozygous: OR=0.96,
      95% CI 0.90-1.03, recessive: OR=0.96, 95% CI 0.90-1.03, dominant: OR=0.94, 95% CI
      0.88-1.01). No evidence of publication bias was observed. CONCLUSION: Meta
      analyses of the available data suggest that CASP8 -652 6N del polymorphism is
      associated with reduced breast cancer risk.

PMID- 24457434
TI  - Venous thromboembolism during hip plaster cast immobilisation: review of the
      literature.
AB  - INTRODUCTION: There is a paucity of data regarding the risk of deep vein
      thrombosis during hip plaster cast immobilisation. The purpose of this article
      was to review the available evidence regarding the incidence of symptomatic
      venous thromboembolism (VTE) during hip plaster cast immobilisation. METHODS AND
      MATERIALS: All papers describing hip plaster cast immobilisation published in the
      English literature retrieved from PubMed, EMBASE and the Cochrane database were
      reviewed. Articles regarding children, hip dysplasia, congenital hip dislocation
      and Legg-Calve-Perthes were excluded. A total of three papers were available for
      analysis. We also describe a case of pulmonary embolism during hip cast
      immobilisation. RESULTS: The overall incidence of symptomatic VTE during hip
      plaster cast immobilisation was 0% in 343 patients. The incidence of symptomatic
      VTE in hip cast brace was 2.3% (range 0-3%). DISCUSSION: Our systematic review of
      the literature showed a paucity of data regarding the incidence of VTE during hip
      plaster cast immobilisation. We describe the first case of pulmonary embolism
      during hip plaster cast immobilisation. We recommend that patients who are fitted
      with a hip plaster cast should be routinely screened for additional risk factors.
      When risk factors are present, patients should be considered for pharmacological
      thromboprophylaxis.

PMID- 24457435
TI  - Incidence of first acute myocardial infarction over time specific for age, sex,
      and country of birth.
AB  - OBJECTIVES: To study the age- and sex-specific incidence rates of first acute
      myocardial infarction (AMI) among first-generation ethnic minority groups
      (henceforth, migrant groups) and the Dutch majority population in the Netherlands
      during two time periods (2000-2004 and 2005-2010). METHODS: Through linkage of
      Dutch nationwide registers, first AMI events in the Dutch majority population and
      the major migrant groups living in the Netherlands were identified from 2000-2004
      and 2005-2010. Absolute incidence rates were calculated within each age-sex
      period-country of birth group. RESULTS: Regardless of ethnic background, AMI
      incidence rates were higher in men than in women and increased with age.
      Incidence significantly declined over time among the Dutch majority population
      (men: -26.8%, women: -26.7%), and among most migrant groups under study. It was
      only in Moroccan migrants that AMI incidence significantly increased over time
      (men: 25.2%, women: 41.7%). Trends differed between age categories, but did not
      show a consistent pattern. The higher AMI incidence in Surinamese men and women
      and Turkish and Indonesian men compared with the Dutch majority population
      persisted over time, but decreased with age and became absent after 70 years of
      age. Moroccans had a significantly lower incidence compared with the Dutch
      majority population during 2000-2004, which disappeared during 2005-2010.
      CONCLUSION: Primary preventive strategies should focus on Surinamese men and
      women and Turkish and Indonesian men below 70 years of age. Future research is
      necessary to unravel the factors that provoke the increasing AMI incidence over
      time among Moroccans.

PMID- 24457436
TI  - Fatal microscopic pulmonary tumour embolisms in patients with breast cancer:
      necessary knowledge for future medical practice.
AB  - Microscopic pulmonary tumour embolisms (MPTE) are a rare but life-threatening
      phenomenon in patients with a history of adenocarcinoma. Due to the nonspecific
      symptoms, diagnostic difficulty, and rapid progression, this condition is often
      fatal. We describe two patients who previously completed breast cancer treatment,
      and now present with fatal MPTE and we provide a comprehensive review of the
      literature. 

PMID- 24457437
TI  - Spots inside out. IgA vasculitis/Henoch-Schonlein purpura.

PMID- 24457438
TI  - A brown-eyed woman with blue discoloration of the sclera. Minocycline-induced
      hyperpigmentation.

PMID- 24457439
TI  - Oesophageal dilatation with pulmonary consolidation. Exogenous lipoid pneumonia
      (ELP).

PMID- 24457440
TI  - A man with "black fingers". Cold agglutinin disease (CAD).

PMID- 24457441
TI  - Delivering high-quality care to patients with a non-Hodgkin's lymphoma: barriers
      perceived by patients and physicians.
AB  - BACKGROUND: Despite the presence of non-Hodgkin's lymphoma (NHL) guidelines,
      there are still gaps between best evidence as described in guidelines and quality
      of care in daily practice. Little is known about factors that affect this
      discrepancy. We aim to identify barriers that influence the delivery of care and
      to explore differences between patients' and physicians' experiences, as well as
      between the different disciplines involved. METHODS: Patients and physicians
      involved in NHL care were interviewed about their experiences with NHL care. The
      barriers identified in these interviews were quantified in a web-based survey.
      Differences were tested using Chi-square tests. RESULTS: Barriers frequently
      perceived by patients concerned lack of patient information and emphatic contact
      (12-43%), long waiting times (19-35%) and lack of guidance and support (39%).
      Most barriers mentioned by physicians concerned the unavailability of the
      guideline (32%), lack of an up-to-date guideline (66%), lack of standardised
      forms for diagnostics (56-70%) and of multidisciplinary meetings (56%). Perceived
      barriers concerning the guideline and standardised forms significantly varied
      between the disciplines involved (range 14-84%, p.

PMID- 24457442
TI  - Severe hypophosphataemia after intravenous iron administration.
AB  - Currently, in many centres, intravenous administration of iron is becoming
      increasingly popular because of higher efficacy and decreased side effects,
      mainly gastrointestinal, compared with oral iron therapy. Studies of intravenous
      ferric carboxymaltose administration in the postpartum setting and in patients
      with non-dialysis-dependent chronic kidney disease revealed a decrease in serum
      phosphate levels that was generally asymptomatic and transient. Here, we report
      four cases of severe and symptomatic hypophosphataemia after intravenous iron
      administration. All patients received this as therapy for iron deficiency anaemia
      due to heavy menstrual bleeding. In most cases, a pre-existent disorder in the
      phosphate homeostasis existed, such as a secondary (cases 3 and 4) or tertiary
      hyperparathyroidism (case 1). However, in the second case there were no risk
      factors for a dysregulation of the phosphate homeostasis. Based on these
      findings, we conclude that severe and symptomatic hypophosphatemia can occur as a
      side effect of intravenous iron administration and can persist for months after
      administration. Especially patients with low phosphate levels prior to therapy
      due to concomitant disorders in phosphate homeostasis (e.g. hyperparathyroidism,
      vitamin D deficiency) are at risk.

PMID- 24457443
TI  - Treatment of hyperglycaemia in diabetic ketoacidosis: natura non facit saltus.
AB  - In the treatment of severe diabetic ketoacidosis the gradual correction of
      glucose, electrolyte and fluid derangements is of utmost importance. In this
      paper the authors provide practical recommendations for these corrections based
      on novel pathophysiological insights. 

PMID- 24457444
TI  - The inversion of the fall: on identity construction in anorexia nervosa.
AB  - Anorexia nervosa can be comprehended as an illness in the broader context of
      Western culture. The myth of the Fall, narrating a forbidden act of eating,
      provides a symbolic background of a philosophical-anthropological comprehension
      of the identity of man, which frames a clinically relevant point of view of
      anorexia nervosa. The formation of identity in its broader anthropological sense
      and particularly with people suffering from anorexia nervosa is subjected to a
      philosophical and psychological analysis consulting the relevant philosophical,
      sociological and psychodynamic literature. The order of eating in terms of
      interdiction and disobedience anthropologically constitutes the identity of men:
      by ignoring the divine taboo, men can reach consciousness and culture. Philosophy
      and psychoanalytical theory have focused on this process regarding an emerging
      capacity to symbolize and on its relation to emancipation and the pursuit of
      autonomy. Under postmodern conditions with a decline of stable cultural value
      systems and traditional structures the process of an emancipatory identity
      construction becomes critical. Surrogates replace missing values; thus,
      injunctions such as to enjoy substitute interdictions. This paper sheds light on
      the impact of these cultural conditions and their postmodern changes on the
      identity construction of anorexia nervosa. Moreover, implications for
      psychotherapeutic treatment are outlined. Besides the medico-scientific models, a
      multifaceted understanding of anorexia nervosa has to consider cultural contexts
      and symbolic processes that matter in the disorder in order to provide a broader
      background for the treatment approach of the anorectic patient.

PMID- 24457445
TI  - Gait disturbance due to foot drop is refractory to treatment in nonsystemic
      vasculitic neuropathy.
AB  - BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is a vasculitis syndrome
      clinically restricted to the peripheral nervous system. Although treatment may
      improve prognosis, daily activities of such patients after treatment have not
      been well studied. METHODS: We evaluated clinical features, laboratory data,
      nerve conduction, and sural nerve biopsy findings for 16 unbiased consecutive
      patients with NSVN. RESULTS: Initial symptoms included neuropathic pain (31%) and
      lower limb sensory disturbance (19%). The mean duration between disease onset and
      initial treatment was 4.1 +/- 4.8 months. Mean modified Rankin scale scores were
      3.13 at hospital admission and 2.69 at final follow-up. The poor outcome group
      had significantly decreased compound muscle action potentials of peroneal nerves
      and significantly more patients presenting with foot drop compared with the good
      outcome group. No other significant differences were found. CONCLUSION:
      Pretreatment foot drop signaled poor outcome in daily activities of patients with
      NSVN, and earlier treatment may be critical for these patients.

PMID- 24457446
TI  - Fabrication and visualization of capillary bridges in slit pore geometry.
AB  - A procedure for creating and imaging capillary bridges in slit-pore geometry is
      presented. High aspect ratio hydrophobic pillars are fabricated and
      functionalized to render their top surfaces hydrophilic. The combination of a
      physical feature (the pillar) with a chemical boundary (the hydrophilic film on
      the top of the pillar) provides both a physical and chemical heterogeneity that
      pins the triple contact line, a necessary feature to create stable long but
      narrow capillary bridges. The substrates with the pillars are attached to glass
      slides and secured into custom holders. The holders are then mounted onto four
      axis microstages and positioned such that the pillars are parallel and facing
      each other. The capillary bridges are formed by introducing a fluid in the gap
      between the two substrates once the separation between the facing pillars has
      been reduced to a few hundred micrometers. The custom microstage is then employed
      to vary the height of the capillary bridge. A CCD camera is positioned to image
      either the length or the width of the capillary bridge to characterize the
      morphology of the fluid interface. Pillars with widths down to 250 um and lengths
      up to 70 mm were fabricated with this method, leading to capillary bridges with
      aspect ratios (length/width) of over 100(1). 

PMID- 24457447
TI  - Co-expression and co-localization of hub proteins and their partners are encoded
      in protein sequence.
AB  - Spatiotemporal coordination is a critical factor in biological processes. Some
      hubs in protein-protein interaction networks tend to be co-expressed and co
      localized with their partners more strongly than others, a difference which is
      arguably related to functional differences between the hubs. Based on numerous
      analyses of yeast hubs, it has been suggested that differences in co-expression
      and co-localization are reflected in the structural and molecular characteristics
      of the hubs. We hypothesized that if indeed differences in co-expression and co
      localization are encoded in the molecular characteristics of the protein, it may
      be possible to predict the tendency for co-expression and co-localization of
      human hubs based on features learned from systematically characterized yeast
      hubs. Thus, we trained a prediction algorithm on hubs from yeast that were
      classified as either strongly or weakly co-expressed and co-localized with their
      partners, and applied the trained model to 800 human hub proteins. We found that
      the algorithm significantly distinguishes between human hubs that are co
      expressed and co-localized with their partners and hubs that are not. The
      prediction is based on sequence derived features such as "stickiness", i.e. the
      existence of multiple putative binding sites that enable multiple simultaneous
      interactions, "plasticity", i.e. the existence of predicted structural disorder
      which conjecturally allows for multiple consecutive interactions with the same
      binding site and predicted subcellular localization. These results suggest that
      spatiotemporal dynamics is encoded, at least in part, in the amino acid sequence
      of the protein and that this encoding is similar in yeast and in human. 

PMID- 24457448
TI  - Triarylborane-dipyrromethane conjugates bearing dual receptor sites: the
      synthesis and evaluation of the anion binding site preference.
AB  - The synthesis and optical properties of four new triarylborane-dipyrromethane
      (TAB-DPM) conjugates (3a-d) containing dual binding sites (hydrogen bond donor
      and Lewis acid) have been reported. The new compounds exhibit a selective
      fluorogenic response towards the F(-) ion. The NMR titrations show that the
      anions bind to the TAB-DPM conjugates via the Lewis acidic triarylborane centre
      in preference to the hydrogen bond donor (dipyrromethane) units.

PMID- 24457449
TI  - Clinical significance of epithelial-mesenchymal transition-associated markers in
      malignant pleural mesothelioma.
AB  - Epithelioid tumors with aggressive behavior have been reported; however, the
      epithelioid type of malignant pleural mesothelioma (MPM) has a less aggressive
      behavior. Few studies have evaluated the prognostic value of epithelial
      mesenchymal transition (EMT) markers in MPM. We hypothesized that mesenchymal
      characteristics might predominate in the tumors. Tumor specimens were collected
      from 33 consecutive patients. We analyzed the EMT expression levels in tumor
      samples by an immunohistochemical analysis. Positive expression of E-cadherin,
      gamma-catenin, vimentin, fibronectin, Twist and YB-1 was observed in 25, 14, 21,
      1, 19 and 18 patients, respectively. No significant association between these
      markers and the clinicopathological characteristics was found. gamma-Catenin
      demonstrated a trend towards decreased expression in sarcomatoid tumors compared
      to epithelioid tumors. On the other hand, a trend was noted towards higher
      expression of vimentin, Twist and YB-1 in sarcomatoid tumors. The survival curves
      demonstrated that the patients with negative gamma-catenin and positive Twist
      staining had a tendency to have a worse prognosis. Although the individual
      proteins might not significantly affect the progression of MPM, the combination
      of gamma-catenin and Twist staining can predict the prognosis of patients with
      MPM.

PMID- 24457450
TI  - Clinicopathologic correlation of textural interface opacities in descemet
      stripping automated endothelial keratoplasty: a case study.
AB  - PURPOSE: The aim of this study was to describe the clinicopathologic correlation
      of textural interface opacities (TIOs) in a Descemet stripping automated
      endothelial keratoplasty (DSAEK) donor button after its removal. METHODS: A 75
      year-old woman underwent combined phacoemulsification with intraocular lens
      placement and DSAEK in her right eye. She had TIOs 1 week postoperatively and
      continued to have poor visual acuity 8 months postoperatively. The original DSAEK
      graft was removed, and a repeat DSAEK procedure with a new donor disc was
      performed. A control corneal button was obtained from a 79-year-old woman who
      suffered chronic rejection and had a failed DSAEK. Both corneal specimens were
      sent for light and electron microscopy. RESULTS: Light microscopy of the donor
      tissue from the patient with TIOs showed stromal irregularities projecting from
      the cut anterior surface and the expected decrease in the endothelial cell
      density associated with the procedure and with artifacts. Electron microscopy
      examination showed irregular collagen fibrils of varying lengths at the stromal
      surface. Light and electron microscopy examination of the donor tissue from the
      control patient showed a smooth anterior stromal surface without projecting
      collagen fibrils. CONCLUSIONS: The histopathology of the endothelial disc from
      the patient with TIOs demonstrated variably irregular lamellae that extended from
      the anterior donor corneal stromal surface. These extending lamellae were absent
      on the anterior stromal surface of the control corneal disc, suggesting that they
      are one possible cause of TIOs and the subsequent suboptimal best-corrected
      visual acuity and quality of vision experienced by a subset of DSAEK-operated
      patients.

PMID- 24457451
TI  - Gamma-irradiated corneas as carriers for the Boston type 1 keratoprosthesis:
      advantages and outcomes in a surgical mission setting.
AB  - PURPOSE: The Boston keratoprosthesis (KPro) is the most commonly used KPro
      worldwide. There are limited data on the outcomes when irradiated corneas are
      used as KPro carriers. We report a retrospective analysis of corneal
      transplantations performed in a regular surgical mission setting in Beirut,
      Lebanon, using the Boston KPro type 1 and gamma-irradiated carrier corneas, and
      we describe visual outcomes, complications, and retention percentage. METHODS: We
      conducted a retrospective analysis of 17 consecutive eyes from 16 patients who
      underwent Boston KPro type 1 implantation at the Beirut Eye Specialist Hospital
      between December 2010 and July 2012. Patient medical records were reviewed for
      preoperative, intraoperative, and postoperative details. RESULTS:
      Postoperatively, 9 (52.9%), 5 (29.4%), and 2 (11.7%) eyes had a corrected visual
      acuity of 20/400 or better, 20/100 or better, and 20/40 or better, respectively,
      at the most recent follow-up visit. A total of 16 eyes (94.1%) improved in
      corrected visual acuity over the course of follow-up. Overall, 13 eyes (76.4%)
      developed at least 1 complication after surgery. Retroprosthetic membrane
      formation was the most common complication, occurring in 10 eyes (58.8%). Neither
      infectious keratitis nor corneal stromal necrosis was noted during the follow-up
      period. The retention percentage was 94.1%. CONCLUSIONS: The visual acuity
      outcomes, incidence of complications, and retention percentage of the KPro using
      gamma-irradiated carrier corneas are comparable with the outcomes of KPro
      implantation reported in the literature using fresh grafts as carriers. KPro with
      irradiated corneal carrier grafts seems to be an effective option to increase the
      supply of transplantation suitable corneas in remote areas, where fresh corneal
      grafts may be scarce.

PMID- 24457453
TI  - Biomechanical efficacy of collagen crosslinking in porcine cornea using a
      femtosecond laser pocket.
AB  - PURPOSE: The aim of this study was to assess the biomechanical efficacy of
      transepithelial collagen crosslinking using the femtosecond laser pocket
      technique compared with that using the standard crosslinking (CXL) technique.
      METHODS: Forty ex vivo porcine eyes were divided into 4 groups with 10 samples
      each. Group 1 comprised the untreated controls. Group 2 was the standard CXL
      group with debridement, instillation of 0.1% riboflavin-dextran solution for 15
      minutes before and every 5 minutes during the 30 minutes of irradiation with
      ultraviolet A (UVA) light of 370 nm and an irradiance of 3 mW/cm2. Group 3
      pertained to the femtolaser pocket control with an intrastromal pocket but
      without riboflavin/UVA. Group 4 was the femtolaser pocket CXL group with an
      intrastromal pocket of an 8-mm diameter at a 180-MUm depth, riboflavin/dextran
      application for 15 minutes and subsequent exposure to UVA light for 30 minutes.
      Postoperatively, biomechanical stress-strain measurements were performed.
      RESULTS: In the standard CXL group, the stress at 10% strain was 207.8 +/- 64.1 *
      10 Pa (+79.45% vs. controls; P = 0.021) compared with 115.8 +/- 20.8 * 10 Pa in
      the untreated control group; in the crosslinked femtolaser pocket group, it was
      159.5 +/- 30.4 * 10 Pa (+37.74%; P = 0.049), in the non-cross-linked femtolaser
      pocket group, it was 103.5 +/- 17.3 * 10 Pa (-10.62%; P = 0.103). The Young
      modulus was 5.4 MPa (+100% vs. controls) in the standard CXL group, 3.7 MPa
      (+37.04%) in the crosslinked femtolaser pocket group, and 2.4 MPa (-11.12%) in
      the non-cross-linked femtolaser pocket group compared with 2.7 MPa in the
      untreated control group. CONCLUSIONS: The biomechanical effect of CXL using the
      femtolaser pocket technique is about 50% less pronounced than that after standard
      CXL. Future studies will show whether the efficacy of the technique can still be
      improved and whether the clinical effect is sufficient for stabilizing ectatic
      corneas.

PMID- 24457452
TI  - Evolving indications for and trends in keratoplasty in British Columbia, Canada,
      from 2002 to 2011: a 10-year review.
AB  - PURPOSE: The aim of this study was to report the evolving indications for
      keratoplasty and the shift in the type of keratoplasty performed in British
      Columbia, Canada, over a 10-year period from 2002 to 2011. METHODS: This was a
      retrospective database review of all the records of corneal transplant tissues at
      the Eye Bank of British Columbia, Canada, from January 2002 to December 2011. The
      patient demographics, indications, and types of transplant performed were
      analyzed. RESULTS: A total of 4843 corneal transplants were performed in 3742
      patients (1968 male and 1774 female) from January 2002 to December 2011. The
      number of keratoplasties performed ranged from 420 in 2008 to 578 in 2011. The
      top 4 indications over the 10-year period were Fuchs endothelial dystrophy (FED;
      18.9%), aphakic/pseudophakic bullous keratopathy (17.4%), regraft (17.1%), and
      keratoconus (15.5%). Penetrating keratoplasty (PKP) accounted for 86.5% (4191
      transplants) of all keratoplasties performed. Since the introduction of Descemet
      stripping automated endothelial keratoplasty (DSAEK) in 2007, there was a
      significant increase in the number of DSAEKs (P < 0.0001) performed and a
      statistical decline in the number of PKPs (P < 0.0001) performed. Despite only 30
      deep anterior lamellar keratoplasties being performed, an increasing trend was
      observed after 2008 (P = 0.0087). A decreasing trend in PKPs and an increasing
      trend in DSAEKs were observed for surgeries performed for FED,
      aphakic/pseudophakic bullous keratopathy, and regraft. CONCLUSIONS: FED has
      become the top indication for performing a keratoplasty over the 10-year period.
      There was a shift from PKP to DSAEK performed for endothelial failure. Although
      the number of deep anterior lamellar keratoplasty surgeries was small, there was
      a significant increasing trend.

PMID- 24457454
TI  - Comparison of tensile strength of slip knots with that of 3-1-1 knots using 10-0
      nylon sutures.
AB  - PURPOSE: The aim of this study was to compare the tensile strength of slip knots
      with that of 3-1-1 knots using 10-0 nylon sutures. METHODS: In vitro, destructive
      materials testing was used. By adhering to the American Standard for Testing and
      Materials standards for testing of suture materials, slip knots were compared
      with 3-1-1 knots using 10-0 nylon suture material. Tensile testing was performed
      on each knot type using the Instron Microtester (Model 5848 Norwood, MA).
      Scanning electron microscopy was used to analyze all sutures tested to failure.
      The main outcome measure was the maximum load (newtons) or ultimate tensile
      strength before which each knot failed by breakage or by unraveling. RESULTS: The
      mean force resulting in failure by breakage of the 3-1-1 knot and slip knot was
      0.71 and 0.64 N, respectively (P = 0.048). The mean force resulting in failure by
      the unraveling of the 3-1-1 knot and slip knot was 0.48 and 0.37 N, respectively
      (P = 0.022). CONCLUSIONS: In 10-0 nylon sutures, the 3-1-1 knot has a
      statistically significant greater tensile strength than the slip knot has in
      conditions wherein they fail by either breakage or unraveling.

PMID- 24457456
TI  - Letter to the editor.

PMID- 24457455
TI  - Topography-based keratoconus progression after corneal collagen crosslinking.
AB  - PURPOSE: The aim of this study was to report 2 cases with topographic keratoconus
      progression despite stability for a long-term period after corneal collagen
      crosslinking (CXL). METHODS: This is a case report. RESULTS: Two patients with
      progressive keratoconus underwent CXL treatment. Four and 5 years
      postoperatively, a topographic examination revealed an increase in the
      keratometric values indicating keratoconus progression. CONCLUSIONS: Post-CXL,
      topographic keratoconus progression may occur several years after, despite
      stability for a long-term period.

PMID- 24457457
TI  - A tale of two letters.

PMID- 24457458
TI  - Ni(II)-salt catalyzed activation of primary amine-sp(3)Calpha-H and cyclization
      with 1,2-diketone to tetrasubstituted imidazoles.
AB  - NiCl2.6H2O and Ni(OAc)2.4H2O were found as efficient catalysts for C-H activation
      of benzyl and aliphatic amines for an unprecedented multi C-N bond forming
      cyclization with 1,2-diketones under refluxing toluene to furnish highly
      substituted and polycyclic imidazoles. 

PMID- 24457459
TI  - The pressure effect on thermotropic cubic phases of 1,2-bis(4'-n
      alkoxybenzoyl)hydrazines.
AB  - The effect of pressure on the nanostructure of a thermotropic cubic (Cub) mesogen
      1,2-bis(4'-n-alkoxybenzoyl)hydrazine (BABH-n; n is the number of carbon atoms in
      the alkyl chain) was investigated under elevated pressures up to 140 MPa by an X
      ray diffraction (XRD) technique. Four compounds, BABH-12, -14, -16 and -18, were
      examined and the type of Cub mesophase formed at ambient pressure is Ia3d for
      BABH-12 and -18, Im3m for BABH-14, and both for BABH-16. The high-pressure XRD
      enabled the discrimination of the Cub phase type in the low-pressure Cub phase
      regions of BABH-14 and BABH-16 and the revision of the phase diagrams reported
      previously. New insight in this work is changes in the lattice constant a of the
      Cub phases upon pressurization. The lattice constant a of the Im3m-Cub phase in
      BABH-14 decreases as only an exception, while those of the Ia3d-Cub phases in
      BABH-16 and -18 increased gradually, with increasing pressure, up to about 24 and
      25% in the unit cell volume, respectively, in their optimal situations of
      pressure and temperature. The a values of the Ia3d-Cub phases in BABH-12, -14, 
      16 and -18 at elevated pressures were roughly on an extrapolated line of the a
      vs. n linear relationship determined for the corresponding data of the short
      chain BABH-n (6 <= n <= 13) at ambient pressure. The pressure-induced expansion
      of the Ia3d-Cub lattice is well explained by reduced lateral expansion of a
      terminal alkyl chain and apparent reduction of the effective core size (from
      "double-layered core" to the "single-layered core" states). 

PMID- 24457460
TI  - STAT6 is amplified in a subset of dedifferentiated liposarcoma.
AB  - A recurrent intrachromosomal rearrangement on chromosome 12q in solitary fibrous
      tumor leads to the formation of a NAB2-STAT6 fusion oncogene. As a result,
      nuclear expression of the cytoplasmic transcription factor STAT6 is found in
      solitary fibrous tumor and serves as a useful diagnostic marker. STAT6 is located
      in 12q13, a region containing well-characterized oncogenes that are commonly
      amplified in dedifferentiated liposarcoma; we have previously reported that STAT6
      is expressed in a subset of dedifferentiated liposarcoma. The aim of this study
      was to determine the frequency of STAT6 expression in dedifferentiated
      liposarcoma and the underlying genetic mechanism. STAT6 protein expression was
      analyzed by immunohistochemistry in a well-characterized series of 35 previously
      unpublished cases of dedifferentiated liposarcoma, all with nuclear MDM2 and/or
      CDK4 expression by immunohistochemistry and/or cytogenetic features of
      dedifferentiated liposarcoma. FISH for STAT6 was performed in all cases with
      STAT6 expression, and a subset of control cases without STAT6 expression. In
      total 4/35 cases (11%) showed STAT6 expression (three with multifocal staining of
      moderate to strong intensity and one with weak focal staining). FISH demonstrated
      amplification of STAT6 in all cases positive for STAT6 by immunohistochemistry;
      in contrast, FISH performed on four STAT6-negative dedifferentiated liposarcomas
      demonstrated no STAT6 amplification (P=0.0286). Of the four STAT6 amplified
      cases, three patients were male and one was female, ranging in age from 51 to 76
      years. Tumors were located in the mediastinum (n=2), paratesticular soft tissue
      (n=1), and perirenal soft tissue (n=1). Three patients received pre-operative
      chemotherapy +/- radiation therapy. In conclusion, STAT6 is amplified in a subset
      of dedifferentiated liposarcoma, resulting in STAT6 protein expression that can
      be detected by immunohistochemistry and may be a potential pitfall in the
      differential diagnosis of dedifferentiated liposarcoma and solitary fibrous
      tumor. These findings suggest a role for STAT6-mediated transcriptional activity
      in some cases of dedifferentiated liposarcoma and highlight the genomic
      complexity and heterogeneity of dedifferentiated liposarcoma. 

PMID- 24457461
TI  - Should mesenteric tumor deposits be included in staging of well-differentiated
      small intestine neuroendocrine tumors?
AB  - Well-differentiated small intestine neuroendocrine tumors can give rise to
      mesenteric tumor deposits, which are not included in the current American Joint
      Committee on Cancer staging system for small intestine neuroendocrine tumors, and
      their impact on patient prognosis is unknown. Seventy-two small intestine
      neuroendocrine tumors resections were identified in our files with slides,
      reports, and follow-up data available. Cases were assessed for T-category and for
      the presence of mesenteric tumor deposits, lymph node metastases, lymphovascular
      invasion, and liver metastases. Mesenteric tumor deposits were defined as
      discrete mesenteric tumor nodules >=1 mm with an irregular growth profile.
      Similar lesions clearly resulting from extranodal extension or direct contiguous
      spread by the primary lesion were excluded. Forty-three of the 72 cases had
      mesenteric tumor deposits (60%). The deposits were significantly associated with
      lymphovascular invasion (P=0.001), pT3 or pT4 disease (P=0.001), nodal metastases
      (P=0.040), and liver metastases (P<0.001) at the time of surgery. In addition,
      four of six cases with tumor deposits and no nodal disease had liver disease.
      Tumor deposits were associated with an increased incidence of disease progression
      and death due to the disease (P=0.001). Finally, the presence of tumor deposits
      at the time of surgery was associated with an increase in hazard of progression
      or death due to disease (hazard ratio: 4.0; 95% confidence interval: 1.3, 12.5;
      P=0.016). Mesenteric tumor deposits are present in the majority of cases of small
      intestine neuroendocrine tumors and are indicators of poor prognosis for this
      disease. Therefore, they may have a place in staging of small intestine
      neuroendocrine tumors, perhaps as analogous to lymph node disease. 

PMID- 24457462
TI  - Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and
      CTAG2 in myxoid and round cell liposarcoma.
AB  - Myxoid and round-cell liposarcoma is a frequently encountered liposarcoma
      subtype. The mainstay of treatment remains surgical excision with or without
      chemoradiation. However, treatment options are limited in the setting of
      metastatic disease. Cancer-testis antigens are immunogenic antigens with the
      expression largely restricted to testicular germ cells and various malignancies,
      making them attractive targets for cancer immunotherapy. Gene expression studies
      have reported the expression of various cancer-testis antigens in liposarcoma,
      with mRNA expression of CTAG1B, CTAG2, MAGEA9, and PRAME described specifically
      in myxoid and round-cell liposarcoma. Herein, we further explore the expression
      of the cancer-testis antigens MAGEA1, ACRBP, PRAME, and SSX2 in myxoid and round
      cell liposarcoma by immunohistochemistry in addition to determining mRNA levels
      of CTAG2 (LAGE-1), PRAME, and MAGEA3 by quantitative real-time PCR. Samples in
      formalin-fixed paraffin-embedded blocks (n=37) and frozen tissue (n=8) were
      obtained for immunohistochemistry and quantitative real-time PCR, respectively.
      Full sections were stained with antibodies to MAGEA1, ACRBP, PRAME, and SSX2 and
      staining was assessed for intensity (1-2+) and percent tumor positivity. The gene
      expression levels of CTAG2, PRAME, and MAGEA3 were measured by quantitative real
      time PCR. In total, 37/37 (100%) of the samples showed predominantly strong,
      homogenous immunoreactivity for PRAME. There was a variable, focal expression of
      MAGEA1 (11%) and SSX2 (16%) and no expression of ACRBP. Quantitative real-time
      PCR demonstrated PRAME and CTAG2 transcripts in all eight samples: six tumors
      with high mRNA levels; two tumors with low mRNA levels. The gene expression of
      MAGEA3 was not detected in the majority of cases. In conclusion, myxoid and round
      cell liposarcomas consistently express PRAME by immunohistochemistry as well as
      CTAG2 and PRAME by qualitative real-time PCR. This supports the use of cancer
      testis antigen-targeted immunotherapy in the treatment of this malignancy. 

PMID- 24457463
TI  - Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male
      breast cancer.
AB  - Male breast cancer is poorly understood with a large proportion arising in the
      familial context particularly with the BRCA2 germline mutation. As phenotypic and
      genotypic differences between sporadic and familial male breast cancers have been
      noted, we investigated the importance of a hypoxic drive in these cancers as this
      pathway has been shown to be of importance in familial female breast cancer.
      Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor
      1alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large
      cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male
      breast cancers showed that 31% of all male breast cancers expressed either HIF1A
      (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with
      an increased incidence of a second-major malignancy (P=0.04), histological tumor
      type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with
      age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression
      of HIF1A was prognostic for disease-specific survival in sporadic male breast
      cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast
      cancer, whereas CA9 was only prognostic in familial male breast cancers (HR:
      358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This
      study found that hypoxic drive is less prevalent in male breast cancer compared
      with female breast cancer, possibly due to a different breast microenvironment.
      The prognostic impact of HIF1A is greatest in sporadic male breast cancers with
      an alternate dominant mechanism for the oncogenic drivers suggested in high risk
      familial male breast cancers. 

PMID- 24457465
TI  - Graphene supported graphone/graphane bilayer nanostructure material for
      spintronics.
AB  - We report an investigation into the magnetic and electronic properties of
      partially hydrogenated vertically aligned few layers graphene (FLG) synthesized
      by microwave plasma enhanced chemical vapor deposition. The FLG samples are
      hydrogenated at different substrate temperatures to alter the degree of
      hydrogenation and their depth profile. The unique morphology of the structure
      gives rise to a unique geometry in which graphane/graphone is supported by
      graphene layers in the bulk, which is very different from other widely studied
      structures such as one-dimensional nanoribbons. Synchrotron based x-ray
      absorption fine structure spectroscopy measurements have been used to investigate
      the electronic structure and the underlying hydrogenation mechanism responsible
      for the magnetic properties. While ferromagnetic interactions seem to be
      predominant, the presence of antiferromagnetic interaction was also observed.
      Free spins available via the conversion of sp(2) to sp(3) hybridized structures,
      and the possibility of unpaired electrons from defects induced upon hydrogenation
      are thought to be likely mechanisms for the observed ferromagnetic orders. 

PMID- 24457466
TI  - Perinatal asphyxia in monochorionic versus dichorionic twins: incidence, risk
      factors and outcome.
AB  - OBJECTIVE: To estimate the incidence, risk factors, severity and outcome after
      perinatal asphyxia in monochorionic (MC) versus dichorionic (DC) twins. METHODS:
      We included all consecutive near-term MC and DC twins with perinatal asphyxia
      admitted to our neonatal ward between 2004 and 2013 and compared the perinatal
      characteristics and neonatal outcome between both groups. RESULTS: The incidence
      of perinatal asphyxia in MC and DC twin infants was 4.0 (11/272) and 4.0% (8/200;
      p = 1.00). In contrast to DC twins, asphyxia in MC twins was strongly associated
      with acute exsanguination and anemia at birth; 64% (7/11) in MC twins and 0%
      (0/8) in DC twins (p < 0.01). Median hemoglobin level at birth in the MC and DC
      groups was 11.5 and 18.6 g/dl, respectively (p < 0.01). CONCLUSIONS: Perinatal
      asphyxia in MC twins is often associated with severe anemia at birth due to acute
      hemorrhage through the placental vascular anastomoses.

PMID- 24457464
TI  - Intratubular germ cell neoplasia of the human testis: heterogeneous protein
      expression and relation to invasive potential.
AB  - Testicular germ cell cancer develops from premalignant intratubular germ cell
      neoplasia, unclassified cells that are believed to arise from failure of normal
      maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre
      spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell
      subpopulations based on stage of germ cell differentiation have been described,
      however the importance of these subpopulations in terms of invasive potential has
      not been reported. We hypothesized that cells expressing an immature
      (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation
      rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)). Therefore, we
      performed triple immunofluorescence and stereology to quantify the different
      intratubular germ cell neoplasia cell subpopulations, based on expression of germ
      cell (OCT4, PLAP, AP2gamma, MAGEA4, VASA) and proliferation (Ki67) markers, in
      testis sections from patients with preinvasive disease, seminoma, and non
      seminoma. We compared these subpopulations with normal human fetal testis and
      with seminoma cells. Heterogeneity of protein expression was demonstrated in
      intratubular germ cell neoplasia cells with respect to gonocyte and
      spermatogonial markers. It included an embryonic/fetal germ cell subpopulation
      lacking expression of the definitive intratubular germ cell neoplasia marker
      OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation.
      OCT4(+)/MAGEA4(-) cells showed a significantly increased rate of proliferation
      compared with the OCT4(+)/MAGEA4(+) population (12.8 versus 3.4%, P<0.0001)
      irrespective of histological tumor type, reflected in the predominance of
      OCT4(+)/MAGEA4(-) cells in the invasive tumor component. Surprisingly,
      OCT4(+)/MAGEA4(-) cells in patients with preinvasive disease showed significantly
      higher proliferation compared to those with seminoma or non-seminoma (18.1 versus
      10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study has
      demonstrated that OCT4(+)/MAGEA4(-) cells are the most frequent and most
      proliferative cell population in tubules containing intratubular germ cell
      neoplasia, which appears to be an important factor in determining invasive
      potential of intratubular germ cell neoplasia to seminomas. 

PMID- 24457468
TI  - Prenatal tricuspid valve size as a predictor of postnatal outcome in patients
      with severe pulmonary stenosis or pulmonary atresia with intact ventricular
      septum.
AB  - INTRODUCTION: Tricuspid valve (TV) size at birth correlates with intervention
      strategy in patients with severe pulmonary stenosis (SPS) or pulmonary
      atresia/intact ventricular septum (PA/IVS). Prenatal features that might predict
      postnatal TV size have not been well studied. We hypothesized that prenatal
      echocardiographic measurements predict the postnatal TV Z-score in fetuses with
      SPS and PA/IVS. MATERIALS AND METHODS: We identified 16 neonates (gestational age
      28 +/- 4.8 weeks) with a fetal diagnosis of SPS or PA/IVS from 2001 to 2010.
      Measurements were performed offline. ROC (receiver operating characteristic)
      analysis was used to generate AUC (areas under the curve) for each of the
      variables. RESULTS: AUC was 0.94 for tricuspid to mitral valve (TV/MV) ratio,
      0.88 for TV Z-score, and 0.85 for TV inflow duration. A cut-off value of >0.63
      for TV/MV yielded a sensitivity of 78%, specificity of 100% for predicting
      postnatal TV Z-score >-3. Neonates with TV Z-score >=-3 and all fetuses with
      antegrade flow across the pulmonary valve or more than moderate tricuspid
      regurgitation had biventricular circulation in follow-up. CONCLUSION: Fetal TV/MV
      >0.63 predicts favorable TV Z-score at birth in patients with SPS and PA/IVS.
      Antegrade pulmonary valve flow and more than moderate tricuspid regurgitation
      also conferred a favorable outcome.

PMID- 24457469
TI  - Tandem repeated application of organic solvents and sodium lauryl sulphate
      enhances cumulative skin irritation.
AB  - The objective of our study was to investigate the tandem irritation potential of
      two organic solvents with concurrent exposure to the hydrophilic detergent
      irritant sodium lauryl sulphate (SLS). A tandem repeated irritation test was
      performed with two undiluted organic solvents, cumene (C) and octane (O), with
      either alternating application with SLS 0.5% or twice daily application of each
      irritant alone in 27 volunteers on the skin of the back. The cumulative
      irritation induced over 4 days was quantified using visual scoring and non
      invasive bioengineering measurements (skin colour reflectance, skin hydration and
      transepidermal water loss). Repeated application of C/SLS and O/SLS induced more
      decline of stratum corneum hydration and higher degrees of clinical irritation
      and erythema compared to each irritant alone. Our results demonstrate a further
      example of additive harmful skin effects induced by particular skin irritants and
      indicate that exposure to organic solvents together with detergents may increase
      the risk of acquiring occupational contact dermatitis.

PMID- 24457467
TI  - Predictors of Heavy Episodic Drinking and Weekly Drunkenness Among Immigrant
      Latinos in North Carolina.
AB  - Few studies have examined correlates of heavy drinking among rural immigrant
      Latino men. This analysis identified correlates of typical week drunkenness and
      past 30-day heavy episodic drinking, within a sample of immigrant Latino men in
      rural North Carolina (n = 258). In the bivariate analyses, Mexican birth,
      entering the United States as an adult, and year-round employment were associated
      with increased odds of typical week drunkenness, and higher acculturation and
      affiliation with a religion with strict prohibitions against drinking alcohol
      were associated with lower odds of typical week drunkenness. Being older, Mexican
      birth, entering the United States as an adult, and lower acculturation were
      associated with increased odds of heavy episodic drinking, and affiliation with a
      religion with strict prohibitions against drinking alcohol and completing high
      school were associated with decreased odds of heavy episodic drinking. In
      multivariable modeling, only religious affiliation was associated with typical
      week drunkenness. Mexican birth, entering the United States as an adult, and
      lower acculturation were associated with increased odds of heavy episodic
      drinking, and affiliation with a religion with strict prohibitions against
      drinking alcohol and completing high school were associated with lower odds of
      heavy episodic drinking. The health of minority men in the United States has been
      neglected, and immigrant Latino men comprise a particularly vulnerable
      population. This analysis provides initial data on some factors associated with
      heavy drinking within a population about which little is known. Future studies
      should examine moderating or mediating factors between age, acculturation,
      religiosity, and heavy drinking that might be targets for behavioral
      interventions. 

PMID- 24457470
TI  - Comparison of gastroesophageal reflux disease questionnaire and multichannel
      intraluminal impedance pH monitoring in identifying patients with chronic cough
      responsive to antireflux therapy.
AB  - BACKGROUND: Empirical therapy has been recommended as an initial clinical
      approach for treating gastroesophageal reflux-induced chronic cough (GERC). This
      study compared the predictive accuracy of the Gastroesophageal Reflux Disease
      Questionnaire (GerdQ) with the accuracy of multichannel intraluminal impedance pH
      monitoring (MII-pH) for GERC. METHODS: A total of 126 consecutive patients with
      potential GERC were recruited to undergo MII-pH and complete the GerdQ. A final
      diagnosis of GERC was made after favorable response to consequent medicinal
      antireflux therapy, regardless of laboratory findings. The predictive accuracy of
      the GerdQ for GERC was assessed and compared with that of MII-pH. RESULTS: GERC
      was confirmed in 102 of 126 patients (81.0%); cough was due to acid reflux in 55
      (53.9%) and nonacid reflux in 47 (46.1%). The optimal cutoff point of the GerdQ
      for predicting GERC was defined as 8.0 according to the highest Youden index of
      0.584, with a sensitivity of 66.7%, specificity of 91.7%, positive predictive
      value of 97.1%, and negative predictive value of 42.9%. A subanalysis for only
      acid GERC showed further improvement in the predictive accuracy of the GerdQ,
      corresponding to a sensitivity of 90.9%, specificity of 78.6%, positive
      predictive value of 71.4%, and negative predictive value of 96.4%. However, a
      meaningful GerdQ cutoff point for prediction of nonacid GERC could not be
      determined. In general, MII-pH was superior to the GerdQ for predicting GERC and
      acid GERC. CONCLUSIONS: The GerdQ can be used for predicting acid GERC but not
      nonacid GERC and is inferior to MII-pH. TRIAL REGISTRY: Chinese Clinical Trial
      Registry; No.: ChiCTR-ODT-12001899; URL: www.chictr.org.

PMID- 24457471
TI  - Dissection of the transversus abdominis muscle for whole-mount neuromuscular
      junction analysis.
AB  - Analysis of neuromuscular junction morphology can give important insight into the
      physiological status of a given motor neuron. Analysis of thin flat muscles can
      offer significant advantage over traditionally used thicker muscles, such as
      those from the hind limb (e.g. gastrocnemius). Thin muscles allow for
      comprehensive overview of the entire innervation pattern for a given muscle,
      which in turn permits identification of selectively vulnerable pools of motor
      neurons. These muscles also allow analysis of parameters such as motor unit size,
      axonal branching, and terminal/nodal sprouting. A common obstacle in using such
      muscles is gaining the technical expertise to dissect them. In this video, we
      detail the protocol for dissecting the transversus abdominis (TVA) muscle from
      young mice and performing immunofluorescence to visualize axons and neuromuscular
      junctions (NMJs). We demonstrate that this technique gives a complete overview of
      the innervation pattern of the TVA muscle and can be used to investigate NMJ
      pathology in a mouse model of the childhood motor neuron disease, spinal muscular
      atrophy.

PMID- 24457472
TI  - Clinical therapeutic effect and biological monitoring of p53 gene in advanced
      hepatocellular carcinoma.
AB  - OBJECTIVE: To investigate the therapeutic effect and biological changes of
      hepatic arterial infusion of p53 gene by the percutaneous port catheter system on
      advanced hepatocellular carcinoma (HCC) through a prospective randomized trial.
      METHODS: A total of 48 patients with advanced HCC between May 2005 and January
      2009 were divided into the treatment group (30) and the control group (18). The
      port catheter system was implanted through the right external iliac artery
      approach in all the cases; the target artery was determined according to the
      manifestation of the angiograph. The patients in the treatment group were given
      arterial infusion of p53 gene (Gendicine, Shenzhen Sibiono GeneTech Co, Ltd) with
      Gendicine (10vp) combined with hydroxycamptothecin (20 mg), once a week, for a
      course continuously for 3 weeks. The arterial infusion with hydroxycamptothecin
      (20 mg) was given to the patients in the control group.
      Pretreatment/posttreatment a fetus protein and Karnofsky Performance Status
      values, change of tumor according to Response Evaluation Criteria in Solid Tumors
      (RECIST), and the survival time were analyzed. Pretreatment/posttreatment
      expression of mutant p53 gene and spontaneous micronucleus formation in the
      peripheral blood were evaluated by flow cytometry and micronucleus test in vivo.
      RESULTS: The patients in the treatment group received 1 to 8 courses of
      treatment, in which the differences between pretreatment/posttreatment AFP and
      KPS values were significant (P < 0.05), whereas there was no significant
      difference (P > 0.05) between pretreatment/posttreatment AFP and KPS values
      within the control group. After 1 month, the survival rates of the treatment and
      control groups (96.6% and 94.4%, respectively) and changes in the tumor evaluated
      according to RECIST were significantly different (P < 0.05) between the 2 groups.
      After 3 months, the survival rates of the treatment and control groups (83.3% and
      55.6%, respectively) and changes in the tumor were also significantly different
      between the 2 groups (P < 0.05). After 6 months, the survival rates (50% and 11%,
      respectively) and changes in the tumor were significantly different between the 2
      groups (P < 0.05). After 9 months, the survival rates (23.3% and 0%,
      respectively) and changes in the tumor were significantly different between the 2
      groups (P < 0.05). Finally, after 12 months, the survival rates (6.67% and 0%,
      respectively) and changes in the tumor were significantly different between the 2
      groups (P < 0.05). The difference between the pretreatment and posttreatment mean
      rates of p53 expression in patients in the treatment group was very significant
      (P < 0.01). The difference between the posttreatment mean rates of the treatment
      group and the control group was also significant. CONCLUSIONS: Sequential therapy
      of p53 gene transcatheter arterial infusion was safe and could prolong the
      survival time of the patients. The biological study will play a positive role in
      guiding and monitoring the aspects of dosage selection and judgment of
      therapeutic efficacy.

PMID- 24457473
TI  - Energy gap in the aetiology of body weight gain and obesity: a challenging
      concept with a complex evaluation and pitfalls.
AB  - The concept of energy gap(s) is useful for understanding the consequence of a
      small daily, weekly, or monthly positive energy balance and the inconspicuous
      shift in weight gain ultimately leading to overweight and obesity. Energy gap is
      a dynamic concept: an initial positive energy gap incurred via an increase in
      energy intake (or a decrease in physical activity) is not constant, may fade out
      with time if the initial conditions are maintained, and depends on the
      'efficiency' with which the readjustment of the energy imbalance gap occurs with
      time. The metabolic response to an energy imbalance gap and the magnitude of the
      energy gap(s) can be estimated by at least two methods, i.e. i) assessment by
      longitudinal overfeeding studies, imposing (by design) an initial positive energy
      imbalance gap; ii) retrospective assessment based on epidemiological surveys,
      whereby the accumulated endogenous energy storage per unit of time is calculated
      from the change in body weight and body composition. In order to illustrate the
      difficulty of accurately assessing an energy gap we have used, as an illustrative
      example, a recent epidemiological study which tracked changes in total energy
      intake (estimated by gross food availability) and body weight over 3 decades in
      the US, combined with total energy expenditure prediction from body weight using
      doubly labelled water data. At the population level, the study attempted to
      assess the cause of the energy gap purported to be entirely due to increased food
      intake. Based on an estimate of change in energy intake judged to be more
      reliable (i.e. in the same study population) and together with calculations of
      simple energetic indices, our analysis suggests that conclusions about the
      fundamental causes of obesity development in a population (excess intake vs. low
      physical activity or both) is clouded by a high level of uncertainty.

PMID- 24457474
TI  - Low frontal assessment battery score as a risk factor for falling in patients
      with Hoehn-Yahr Stage III Parkinson's disease: a 2-year prospective study.
AB  - BACKGROUND: Recently, we evaluated factors responsible for falling, including
      walking speed evaluated with the use of originally designed, suddenly narrowed
      paths, in patients with Hoehn-Yahr stage III PD. We prospectively studied the
      same cohort of patients with PD who were followed up for 2 years, to determine
      predictors of future falls. METHODS: We performed clinical assessments and
      evaluated balance in 26 patients. A total of 19 variables including PD-related
      independent variables, balance investigation-related independent variables and
      gait independent-related variables were evaluated. RESULTS: The Frontal
      Assessment Battery (FAB) score (p = 0.002), Tinetti balance (p = 0.009), and gait
      velocity (p = 0.001) were higher in fallers than in non-fallers. On multiple
      logistic regression analysis, the FAB score was related to falling (odds ratio =
      3.328, p = 0.033, 95% confidence interval = 1.104-10.03). On the FAB, the scores
      of 'inhibitory control' and 'sensitivity to interference' were significantly
      lower in fallers than in non-fallers. CONCLUSIONS: The use of the originally
      designed, suddenly narrowed path was the primary reason for demonstrating for the
      first time that a low FAB score is a risk factor for future falls. Calculation of
      the FAB score may be useful for predicting the risk of future falls.

PMID- 24457475
TI  - T cells: Skin oils trigger T cell responses.

PMID- 24457476
TI  - T cells: Spotting the troublemakers.

PMID- 24457477
TI  - Asthma and allergy: Diet and airway inflammation.

PMID- 24457478
TI  - Immunogenetics: Ethnic differences in sensitivity to H7N9 virus.

PMID- 24457481
TI  - Mucosal immunology: Innate control of IgA.

PMID- 24457486
TI  - Lipopolysaccharide (LPS) from the cellular wall of Gram-negative bacteria, also
      known as endotoxin, is a key molecule in the pathogenesis of sepsis and septic
      shock. Preface.

PMID- 24457487
TI  - State of the art in the clinical treatment of endotoxic shock.
AB  - Sepsis is a major health problem and remains an important cause of death
      worldwide. The failure to convert advances in our understanding of the biologic
      features of sepsis into effective new therapies questions the current approach to
      the development of sepsis drugs, and suggests a need for newer and better
      clinical trial design. Blood purification for sepsis is a promising therapeutic
      strategy to improve survival and reduce organ failure in patients with severe
      sepsis and septic shock.

PMID- 24457488
TI  - Endotoxin removal: history of a mission.
AB  - One of the key molecules involved in the pathogenesis of severe sepsis and septic
      shock is lipopolysaccharide (LPS) or endotoxin, which is a component of the
      cellular wall of Gram-negative bacteria. Clinical studies have shown that the
      level of circulating LPS is correlated with illness severity (APACHE II), the
      onset and amount of organ dysfunction (SOFA) and intensive care unit mortality.
      Many therapeutic strategies have attempted to neutralize the pathogenic activity
      of endotoxin in order to interrupt the progression of a septic state towards a
      worsened clinical framework, i.e. severe sepsis of septic shock. Over the past
      decades the role of extracorporeal hemoperfusion by means of polymyxin B-based
      cartridges (PMX-DHP) to bind and neutralize LPS from whole blood has increased in
      clinical relevance. This is due to an increasing number of studies confirming
      that a directed therapy of endotoxic shock could significantly influence the
      course of the septic cascade. This review will outline the meaning of the
      targeted approach to endotoxin, both highlighting the specific immunologic effect
      of endotoxin removal by polymyxin B and the evidence of clinical improvements
      following this kind of therapy in terms of recovery of organ function.

PMID- 24457485
TI  - Innate immunity to Toxoplasma gondii infection.
AB  - Toxoplasma gondii is a protozoan parasite of global importance. In the laboratory
      setting, T. gondii is frequently used as a model pathogen to study mechanisms of
      T helper 1 (TH1) cell-mediated immunity to intracellular infections. However,
      recent discoveries have shown that innate type 1 immune responses that involve
      interferon-gamma (IFNgamma)-producing natural killer (NK) cells and neutrophils,
      rather than IFNgamma-producing T cells, predetermine host resistance to T.
      gondii. This Review summarizes the Toll-like receptor (TLR)-dependent mechanisms
      that are responsible for parasite recognition and for the induction of IFNgamma
      production by NK cells, as well as the emerging data about the TLR-independent
      mechanisms that lead to the IFNgamma-mediated elimination of T. gondii. 

PMID- 24457489
TI  - New trends in polymyxin B hemoperfusion: from 2006 to 2013.
AB  - Endotoxin, one of the principal components on the outer membrane of Gram-negative
      bacteria, is considered a key and early component in the pathogenesis of sepsis.
      Polymyxin B bound to polystyrene fibers (PMX) is a medical device capable of
      removing circulating endotoxin by adsorption. The most comprehensive analysis to
      date of clinical experience with this device remains a meta-analysis of 28
      studies between 1998 and 2006. This showed that PMX hemoperfusion was associated
      with improved blood pressure and a reduction in dopamine dose, improved PaO2/FiO2
      ratio and lower mortality. Since this meta-analysis, over 50 additional studies
      on PMX have been published. The majority are observational, with small sample
      sizes. Notable among the newer studies is the increasing interest in the use of
      PMX therapy in interstitial pneumonias and idiopathic pulmonary fibrosis, as well
      as in longer treatment duration and earlier initiation of PMX therapy in an
      attempt to further improve clinical outcomes. These observational data highlight
      important aspects of PMX therapy worthy of more rigorous investigation in future
      studies.

PMID- 24457490
TI  - Endotoxin removal: bringing the mission to North America.
AB  - The EUPHRATES trial (Evaluating Use of Polymyxin B Hemoperfusion in a Randomized
      Controlled Trial of Adults Treated for Endotoxemia and Septic Shock) is the first
      biomarker-driven trial in sepsis. This unique trial is being run in a blinded
      manner, further contributing to the robustness of its design. This paper will
      describe the implementation of the EUPHRATES trial focusing on 3 pertinent
      features: (1) managing (and maintaining) the blinding of a medical device trial;
      (2) impact of the use of a diagnostic test where eligible subjects with septic
      shock must also have high levels of endotoxin (>= 0.60 EAA units), and (3)
      managing enrolment in a complicated trial design where two medical teams are
      involved (the intensivist as the blinded caregiver and nephrologists as the
      unblinded performers of the intervention). The study is nearing the halfway mark
      and is currently experiencing excellent recruitment success.

PMID- 24457491
TI  - Future options for (economically) sustainable research in sepsis.
AB  - The relentless increase in healthcare costs and the global economic crisis
      require us to rethink the way research is done. The heterogeneity of patients is
      a major challenge in designing and coordinating high-quality studies about
      sepsis. Studies on new treatments and devices, such as polymyxin B hemoperfusion,
      must be optimized not only for potential benefits for a specific population (i.e.
      efficacy), but also for their eventual implementation in real-world situations
      (i.e. effectiveness) and for economic costs (i.e. efficiency). In this regard,
      theragnosis and newer statistical tools could help us obtain useful information
      from real-life observational data. In this review, we discuss the basic
      components required for sustainable research in polymyxin B hemoperfusion.

PMID- 24457493
TI  - Presenting symptoms of pediatric brain tumors diagnosed in the emergency
      department.
AB  - OBJECTIVE: The primary objective of this study is to categorize the symptoms
      associated with brain tumors as diagnosed in the emergency department (ED). The
      secondary objective is to detail the specific characteristics of these headaches
      via a subgroup analysis. METHODS: A retrospective chart review was performed
      among patients younger than 18 years presenting to a large urban tertiary care
      facility. Electronic medical records were searched and reviewed from 2002 to 2011
      for inpatient discharge diagnoses using malignant and benign central nervous
      system tumor International Classification of Diseases, Ninth Revision codes.
      RESULTS: The electronic records of ED visits for 87 patients were reviewed. The
      most frequent signs and symptoms were as follows: headache (66.7%), hydrocephalus
      (58.6%), nausea/vomiting (49.4%), gait disturbance (42.5%), vision changes
      (20.7%), seizure (17.2%), behavior/school change (17.2%), cranial nerve deficits
      (16.1%), altered mental status (16.1%), back/neck pain (16.1%), papilledema
      (12.6%), facial asymmetry (10.3%), sensory deficits (8.0%), focal motor weakness
      (6.9%), cranial nerve 6 deficit (6.9%), ptosis (5.7%), macrocephaly (4.6%),
      asymptomatic (3.4%), and anisocoria (1.1%). The frequencies of location of
      headache were diffuse (24.1%), frontal (12.1%), occipital (8.6%), and
      parietal/temporal (6.9%). The severity was described as severe (37.9%) followed
      by moderate and mild (10.3% and 5.2%, respectively). Most headaches occurred in
      the morning (13.8%) and night (12.1%), and their quality was predominantly
      progressively worsening (50.0%) CONCLUSIONS: Brain tumors diagnosed in the ED
      most commonly present with headache, hydrocephalus, nausea/vomiting, and gate
      disturbances. The headaches are described as progressively worsening and diffuse
      most commonly occurring in the morning and night.

PMID- 24457492
TI  - Polymyxin B hemoperfusion in clinical practice: the picture from an unbound
      collaborative registry.
AB  - After the publication of the EUPHAS trial, the clinical use of polymyxin B
      hemoperfusion (Toraymyxin(r)) increased significantly in Italy. Nevertheless, no
      structured data collections have been carried out to underline the
      characteristics of treated patients. Therefore, a collaborative registry of
      clinical data was promoted among users in order to better define the structure of
      the prospective data collection named the EUPHAS2 project. Neither inclusion
      criteria nor therapeutic constraints were imposed, highlighting adherence to
      clinical evidence provided by previous randomized controlled trials, and also
      unusual or borderline practice in the selection of patients for polymyxin B-based
      cartridges (PMX-DHP). This first retrospective phase of data collection included
      patients with severe sepsis and septic shock treated with Toraymyxin over the
      last 3 years, up to July 2013. Thirty-one hospitals participated in the EUPHAS2
      study, collecting data on 306 patients. Enrolled patients were grouped according
      to the main source of sepsis: abdominal (41.8%) and nonabdominal (58.2%). The
      abdominal patients had characteristics well matching those selected for the
      EUPHAS randomized controlled trial in terms of time-to-enrolment, severity of the
      illness, 28-day mortality and in-hospital mortality. Their 28-day mortality rate
      was 35% with a significant reduction of the Sequential Organ Failure Assessment
      Score (SOFA) score after 72 h of treatment (p < 0.001). Patients with
      nonabdominal sepsis were heterogeneous and only a few of them had their endotoxin
      activity tested in a manner not allowing a reliable evaluation of the real
      efficacy of the treatment and organ dysfunction control. Their 28-day mortality
      rate was 49% and the SOFA score did not significantly change before and after
      treatment. In conclusion, clinical experience confirms the results of the
      original EUPHAS randomized trial in terms of outcome for patients with abdominal
      severe sepsis. Specific studies focused on a population of patients with Gram
      negative infections of nonabdominal origin are needed before recommending
      treatment with Toraymyxin as an effective therapy.

PMID- 24457494
TI  - Providing adolescent sexual health care in the pediatric emergency department:
      views of health care providers.
AB  - OBJECTIVES: The purpose of this study was to explore health care providers'
      (HCPs') attitudes and beliefs about adolescent sexual health care provision in
      the emergency department (ED) and to identify barriers to a health educator-based
      intervention. METHODS: We conducted focused, semistructured interviews of HCPs
      from the ED and adolescent clinic of a children's hospital. The interview guide
      was based on the theory of planned behavior and its constructs: attitudes,
      subjective norms, perceived behavioral control, and intention to facilitate care.
      We used purposive sampling and enrollment continued until themes were saturated.
      Interviews were recorded and transcribed. Transcripts were analyzed using
      directed content analysis. RESULTS: Twenty-nine interviews were required for
      saturation. Participants were 12 physicians, 12 nurses, 3 nurse practitioners,
      and 2 social workers; the majority (83%) were female. Intention to facilitate
      care was influenced by HCP perception of (1) their professional role, (2) the
      role of the ED (focused vs expanded care), and (3) need for patient safety.
      Health care providers identified 3 practice referents: patients/families, peers
      and administrators, and professional organizations. Health care providers
      perceived limited behavioral control over care delivery because of time
      constraints, confidentiality issues, and comfort level. There was overall support
      for a health educator, and many felt the educator could help overcome barriers to
      care. CONCLUSIONS: Despite challenges unique to the ED, HCPs were supportive of
      the intervention and perceived the health educator as a resource to improve
      adolescent care and services. Future research should evaluate efficacy and costs
      of a health educator in this setting.

PMID- 24457495
TI  - A new positive-pressure device for nasal foreign body removal.
AB  - OBJECTIVES: Nasal foreign bodies (FBs) are common causes of pediatric emergency
      consultations. The different methods for removing nasal FBs have varying levels
      of efficacy. The aim of this study was to evaluate the safety and efficacy of a
      new device for nasal FB removal in children. METHODS: A nasal occlusion device
      that uses modulated positive pressure to remove FBs was evaluated in a series of
      18 patients ranging in age from 1 to 8 years diagnosed with a nasal FB during a
      period of 7 months. RESULTS: The device successfully removed FBs in 17 (94.4%) of
      the 18 patients. In 12 of the cases (66.7%), the FB was removed during the first
      attempt. None of the patients had complications or sequelae at the time of
      removal or at the follow-up visit. CONCLUSIONS: The nasal occlusion device used
      in this study was found to be a promising, safe, effective, and easy to use tool
      for FB removal in a pediatric emergency room setting.

PMID- 24457496
TI  - Respiratory diseases in pediatric triage: a comparison between a general
      emergency department and a pediatric emergency department.
AB  - OBJECTIVE: In this study, the authors have compared data concerning the pediatric
      triage that is carried out in 2 large emergency departments (EDs) in Rome, one
      located in a university pediatric clinic with qualified staff and the other one
      in a general hospital with a high flow of users and pediatric admissions.
      METHODS: A total of 324 children were selected (162 per hospital) with ages
      between 0 and 3 years who went to the ED in the period from October to December
      2009 for respiratory pathologic findings at the lower respiratory tracts'
      expense. We took and compared the following data: assignation of the color code,
      congruity of the color code, and realization of the reevaluation. DISCUSSION:
      This study reveals several differences between the 2 structures considered with a
      clear tendency of nurses of the general ED to underestimate color codes, giving
      undertriage rates in a significant number of cases. Another significantly
      important difference was found on the detection of children's vital parameters.
      One last important parameter that emerged from this study was the lack of
      attention to the reevaluation of the patient after admission in ED. RESULTS: In
      the light of what we pointed out, it is necessary to implement the educational
      and informative quality of the triage operators and educators, planning
      periodical triage training courses to reduce errors. Particular emphasis must be
      placed on providing pediatric continuing education for nurses practicing in
      general ED.

PMID- 24457497
TI  - Pediatric early warning score at time of emergency department disposition is
      associated with level of care.
AB  - OBJECTIVE: The objective of this study was to determine the association between
      the Pediatric Early Warning Score (PEWS) at time of emergency department (ED)
      disposition and level of care. METHODS: We conducted a prospective observational
      study with a convenience sample of patients aged 0 to 21 years in the ED of an
      urban, tertiary care children's hospital between November 2010 and July 2011.
      Pediatric Early Warning Score data were obtained at time of ED disposition, and
      the disposition decision was collected from the electronic medical record.
      Multinomial logistic regression was used to determine the association between
      PEWS and disposition. RESULTS: The sample of 383 patients included 239 (62%) who
      were discharged, 126 (33%) admitted to acute care, and 18 (5%) admitted to
      intensive care. Assigned scores ranged from 0 to 9. Adjusting for triage level, a
      1-point increase in PEWS increased the odds of acute care admission 48% relative
      to the odds of discharge (odds ratio, 1.48; 95% confidence interval, 1.25-1.76)
      and increased the odds of intensive care admission 41% relative to the odds of
      acute care admission (odds ratio, 1.41; 95% confidence interval, 1.13-1.76).
      Pediatric Early Warning Score of 1 or more had maximum discriminant ability for
      admission, and PEWS of 3 or greater had maximum discriminant ability for
      intensive care. Area under the receiver operator characteristic curve was 0.68 to
      detect need for admission for the entire sample and 0.80 among the 97 patients
      with respiratory complaints. CONCLUSIONS: Pediatric Early Warning Score is
      associated with the level of care at ED disposition but does not provide adequate
      sensitivity and specificity to be used in isolation. Performance characteristics
      are better for patients with respiratory complaints.

PMID- 24457499
TI  - Bimetallic ruthenium complexes bridged by divinylphenylene bearing oligo(ethylene
      glycol)methylether: synthesis, (spectro)electrochemistry and the lithium cation
      effect.
AB  - A series of 1,4-disubstituted ruthenium-vinyl complexes, (E,E)
      [{(PMe3)3(CO)ClRu}2(MU-HC=CH-Ar-CH=CH)], in which the 1,4-diethenylphenylene
      bridge bears two oligo(ethylene glycol)methyl ether side chains at different
      positions (2,5- and 2,3-positions), were prepared. The respective products were
      characterized by elemental analyses and NMR spectroscopy. The structures of
      complexes 1b and 1e were established by X-ray crystallography. The electronic
      properties of the complexes were investigated by cyclic voltammetry, and IR and
      UV-vis/NIR spectroscopies. Electrochemical studies showed that the 2,5
      substituents better stabilized the mixed-valence states; the electrochemical
      behavior was greatly affected by lithium cations, especially complex 1g with 2,3
      substituents, which was further supported by IR and UV-vis/NIR spectra changes.
      Spectroelectrochemical studies showed that the redox chemistry was dominated by
      the non-innocent character of the bridging fragment.

PMID- 24457498
TI  - Standardized process used in the emergency department for pediatric oncology
      patients with fever and neutropenia improves time to the first dose of
      antibiotics.
AB  - OBJECTIVES: This study aimed to evaluate the effect of a standardized process on
      time to the first dose of antibiotics in pediatric oncology patients presenting
      to the emergency department (ED) with fever and neutropenia (F-N). METHODS: A
      standardized process and order set were created to be used on all pediatric
      febrile neutropenic patients who presented to the ED of a large academic
      children's hospital. The order set was used for patients with a known oncologic
      diagnosis, a fever greater than 38.3 degrees C, and who were presumed or known to
      be neutropenic. A retrospective chart review was then performed for the 18 months
      before and the 6 months after implementation of the new process to evaluate if
      the time to the first dose of antibiotics was significantly reduced. RESULTS: A
      total of 130 occurrences of F-N were analyzed. This included 100 episodes before
      the implementation of the new process and 30 episodes afterward. The time to
      antibiotics being ordered was reduced by over half, with a median time of 72
      minutes preprocess and 27 minutes postprocess implementation (P = 0.04). Median
      time from the arrival in the ED to the administration of the first dose of
      antibiotics was reduced by almost an hour, taking 154 minutes before the new
      process compared with 95 minutes after its implementation (P = 0.0001).
      CONCLUSIONS: The use of a standardized process that uses a standardized order set
      can reduce the time to the first dose of antibiotics in pediatric oncology
      patients with F-N.

PMID- 24457500
TI  - Structural, electronic, and photophysical properties of thieno-expanded tricyclic
      purine analogs: a theoretical study.
AB  - Modified forms of DNA are under intense research because of their potential
      applications in nanotechnology and medical science. In the present work,
      comprehensive theoretical investigations into the structural, electronic, and
      optical properties of four newly designed thieno-expanded base analogs, namely
      ttA, ttG, ttX, and ttHX, have been performed. The results are compared against
      the findings obtained for the natural ones. Geometrically, ttA and ttG have
      nonplanar ground-state geometries caused by the pyramidalization of the amino
      groups, while ttX and ttHX have planar geometries. Electronically, the ionization
      potentials and HOMO-LUMO gaps are smaller than natural ones, while the electron
      affinities are larger than natural ones. The nature of the low-lying excited
      states is discussed, and it was found that the lowest transitions are of pipi*
      nature and were mainly dominated by the configuration HOMO -> LUMO. The
      calculated excitation maxima are 283, 302, 294, and 290 nm for ttA, ttG, ttX, and
      ttHX, respectively, and they are greatly red-shifted compared with natural bases.
      In the gas phase, the fluorescence from them would be expected to occur around
      291, 331, 317, and 323 nm, respectively. The effects of micro-hydration, bulk
      water solution, and base pairing with their complementary natural bases on the
      low-lying electronic transitions of these modified bases were also examined. 

PMID- 24457501
TI  - A hierarchical word-merging algorithm with class separability measure.
AB  - In image recognition with the bag-of-features model, a small-sized visual
      codebook is usually preferred to obtain a low-dimensional histogram
      representation and high computational efficiency. Such a visual codebook has to
      be discriminative enough to achieve excellent recognition performance. To create
      a compact and discriminative codebook, in this paper we propose to merge the
      visual words in a large-sized initial codebook by maximally preserving class
      separability. We first show that this results in a difficult optimization
      problem. To deal with this situation, we devise a suboptimal but very efficient
      hierarchical word-merging algorithm, which optimally merges two words at each
      level of the hierarchy. By exploiting the characteristics of the class
      separability measure and designing a novel indexing structure, the proposed
      algorithm can hierarchically merge 10,000 visual words down to two words in
      merely 90 seconds. Also, to show the properties of the proposed algorithm and
      reveal its advantages, we conduct detailed theoretical analysis to compare it
      with another hierarchical word-merging algorithm that maximally preserves mutual
      information, obtaining interesting findings. Experimental studies are conducted
      to verify the effectiveness of the proposed algorithm on multiple benchmark data
      sets. As shown, it can efficiently produce more compact and discriminative
      codebooks than the state-of-the-art hierarchical word-merging algorithms,
      especially when the size of the codebook is significantly reduced. 

PMID- 24457502
TI  - Animated pose templates for modeling and detecting human actions.
AB  - This paper presents animated pose templates (APTs) for detecting short-term, long
      term, and contextual actions from cluttered scenes in videos. Each pose template
      consists of two components: 1) a shape template with deformable parts represented
      in an And-node whose appearances are represented by the Histogram of Oriented
      Gradient (HOG) features, and 2) a motion template specifying the motion of the
      parts by the Histogram of Optical-Flows (HOF) features. A shape template may have
      more than one motion template represented by an Or-node. Therefore, each action
      is defined as a mixture (Or-node) of pose templates in an And-Or tree structure.
      While this pose template is suitable for detecting short-term action snippets in
      two to five frames, we extend it in two ways: 1) For long-term actions, we
      animate the pose templates by adding temporal constraints in a Hidden Markov
      Model (HMM), and 2) for contextual actions, we treat contextual objects as
      additional parts of the pose templates and add constraints that encode spatial
      correlations between parts. To train the model, we manually annotate part
      locations on several keyframes of each video and cluster them into pose templates
      using EM. This leaves the unknown parameters for our learning algorithm in two
      groups: 1) latent variables for the unannotated frames including pose-IDs and
      part locations, 2) model parameters shared by all training samples such as
      weights for HOG and HOF features, canonical part locations of each pose,
      coefficients penalizing pose-transition and part-deformation. To learn these
      parameters, we introduce a semi-supervised structural SVM algorithm that iterates
      between two steps: 1) learning (updating) model parameters using labeled data by
      solving a structural SVM optimization, and 2) imputing missing variables (i.e.,
      detecting actions on unlabeled frames) with parameters learned from the previous
      step and progressively accepting high-score frames as newly labeled examples.
      This algorithm belongs to a family of optimization methods known as the Concave
      Convex Procedure (CCCP) that converge to a local optimal solution. The inference
      algorithm consists of two components: 1) Detecting top candidates for the pose
      templates, and 2) computing the sequence of pose templates. Both are done by
      dynamic programming or, more precisely, beam search. In experiments, we
      demonstrate that this method is capable of discovering salient poses of actions
      as well as interactions with contextual objects. We test our method on several
      public action data sets and a challenging outdoor contextual action data set
      collected by ourselves. The results show that our model achieves comparable or
      better performance compared to state-of-the-art methods. 

PMID- 24457503
TI  - Attribute-based classification for zero-shot visual object categorization.
AB  - We study the problem of object recognition for categories for which we have no
      training examples, a task also called zero--data or zero-shot learning. This
      situation has hardly been studied in computer vision research, even though it
      occurs frequently; the world contains tens of thousands of different object
      classes, and image collections have been formed and suitably annotated for only a
      few of them. To tackle the problem, we introduce attribute-based classification:
      Objects are identified based on a high-level description that is phrased in terms
      of semantic attributes, such as the object's color or shape. Because the
      identification of each such property transcends the specific learning task at
      hand, the attribute classifiers can be prelearned independently, for example,
      from existing image data sets unrelated to the current task. Afterward, new
      classes can be detected based on their attribute representation, without the need
      for a new training phase. In this paper, we also introduce a new data set,
      Animals with Attributes, of over 30,000 images of 50 animal classes, annotated
      with 85 semantic attributes. Extensive experiments on this and two more data sets
      show that attribute-based classification indeed is able to categorize images
      without access to any training images of the target classes.

PMID- 24457504
TI  - Automatic alignment of genus-zero surfaces.
AB  - A new algorithm is presented that provides a constructive way to conformally warp
      a triangular mesh of genus zero to a destination surface with minimal metric
      deformation, as well as a means to compute automatically a measure of the
      geometric difference between two surfaces of genus zero. The algorithm takes as
      input a pair of surfaces that are topological 2-spheres, each surface given by a
      distinct triangulation. The algorithm then constructs a map $(f)$ between the two
      surfaces. First, each of the two triangular meshes is mapped to the unit sphere
      using a discrete conformal mapping algorithm. The two mappings are then composed
      with a Mobius transformation to generate the function $(f)$. The Mobius
      transformation is chosen by minimizing an energy that measures the distance of
      $(f)$ from an isometry. We illustrate our approach using several "real life" data
      sets. We show first that the algorithm allows for accurate, automatic, and
      landmark-free nonrigid registration of brain surfaces. We then validate our
      approach by comparing shapes of proteins. We provide numerical experiments to
      demonstrate that the distances computed with our algorithm between low
      resolution, surface-based representations of proteins are highly correlated with
      the corresponding distances computed between high-resolution, atomistic models
      for the same proteins. 

PMID- 24457505
TI  - Fast and scalable approximate spectral matching for higher order graph matching.
AB  - This paper presents a fast and efficient computational approach to higher order
      spectral graph matching. Exploiting the redundancy in a tensor representing the
      affinity between feature points, we approximate the affinity tensor with the
      linear combination of Kronecker products between bases and index tensors. The
      bases and index tensors are highly compressed representations of the approximated
      affinity tensor, requiring much smaller memory than in previous methods, which
      store the full affinity tensor. We compute the principal eigenvector of the
      approximated affinity tensor using the small bases and index tensors without
      explicitly storing the approximated tensor. To compensate for the loss of
      matching accuracy by the approximation, we also adopt and incorporate a
      marginalization scheme that maps a higher order tensor to matrix as well as a one
      to-one mapping constraint into the eigenvector computation process. The
      experimental results show that the proposed method is faster and requires smaller
      memory than the existing methods with little or no loss of accuracy. 

PMID- 24457506
TI  - Feature coding in image classification: a comprehensive study.
AB  - Image classification is a hot topic in computer vision and pattern recognition.
      Feature coding, as a key component of image classification, has been widely
      studied over the past several years, and a number of coding algorithms have been
      proposed. However, there is no comprehensive study concerning the connections
      between different coding methods, especially how they have evolved. In this
      paper, we first make a survey on various feature coding methods, including their
      motivations and mathematical representations, and then exploit their relations,
      based on which a taxonomy is proposed to reveal their evolution. Further, we
      summarize the main characteristics of current algorithms, each of which is shared
      by several coding strategies. Finally, we choose several representatives from
      different kinds of coding approaches and empirically evaluate them with respect
      to the size of the codebook and the number of training samples on several widely
      used databases (15-Scenes, Caltech-256, PASCAL VOC07, and SUN397). Experimental
      findings firmly justify our theoretical analysis, which is expected to benefit
      both practical applications and future research.

PMID- 24457507
TI  - Good practice in large-scale learning for image classification.
AB  - We benchmark several SVM objective functions for large-scale image
      classification. We consider one-versus-rest, multiclass, ranking, and weighted
      approximate ranking SVMs. A comparison of online and batch methods for optimizing
      the objectives shows that online methods perform as well as batch methods in
      terms of classification accuracy, but with a significant gain in training speed.
      Using stochastic gradient descent, we can scale the training to millions of
      images and thousands of classes. Our experimental evaluation shows that ranking
      based algorithms do not outperform the one-versus-rest strategy when a large
      number of training examples are used. Furthermore, the gap in accuracy between
      the different algorithms shrinks as the dimension of the features increases. We
      also show that learning through cross-validation the optimal rebalancing of
      positive and negative examples can result in a significant improvement for the
      one-versus-rest strategy. Finally, early stopping can be used as an effective
      regularization strategy when training with online algorithms. Following these
      "good practices," we were able to improve the state of the art on a large subset
      of 10K classes and 9M images of ImageNet from 16.7 percent Top-1 accuracy to 19.1
      percent.

PMID- 24457508
TI  - On the role of correlation and abstraction in cross-modal multimedia retrieval.
AB  - The problem of cross-modal retrieval from multimedia repositories is considered.
      This problem addresses the design of retrieval systems that support queries
      across content modalities, for example, using an image to search for texts. A
      mathematical formulation is proposed, equating the design of cross-modal
      retrieval systems to that of isomorphic feature spaces for different content
      modalities. Two hypotheses are then investigated regarding the fundamental
      attributes of these spaces. The first is that low-level cross-modal correlations
      should be accounted for. The second is that the space should enable semantic
      abstraction. Three new solutions to the cross-modal retrieval problem are then
      derived from these hypotheses: correlation matching (CM), an unsupervised method
      which models cross-modal correlations, semantic matching (SM), a supervised
      technique that relies on semantic representation, and semantic correlation
      matching (SCM), which combines both. An extensive evaluation of retrieval
      performance is conducted to test the validity of the hypotheses. All approaches
      are shown successful for text retrieval in response to image queries and vice
      versa. It is concluded that both hypotheses hold, in a complementary form,
      although evidence in favor of the abstraction hypothesis is stronger than that
      for correlation. 

PMID- 24457509
TI  - Online multiple kernel similarity learning for visual search.
AB  - Recent years have witnessed a number of studies on distance metric learning to
      improve visual similarity search in content-based image retrieval (CBIR). Despite
      their successes, most existing methods on distance metric learning are limited in
      two aspects. First, they usually assume the target proximity function follows the
      family of Mahalanobis distances, which limits their capacity of measuring
      similarity of complex patterns in real applications. Second, they often cannot
      effectively handle the similarity measure of multimodal data that may originate
      from multiple resources. To overcome these limitations, this paper investigates
      an online kernel similarity learning framework for learning kernel-based
      proximity functions which goes beyond the conventional linear distance metric
      learning approaches. Based on the framework, we propose a novel online multiple
      kernel similarity (OMKS) learning method which learns a flexible nonlinear
      proximity function with multiple kernels to improve visual similarity search in
      CBIR. We evaluate the proposed technique for CBIR on a variety of image data sets
      in which encouraging results show that OMKS outperforms the state-of-the-art
      techniques significantly.

PMID- 24457510
TI  - Retrieval-based face annotation by weak label regularized local coordinate
      coding.
AB  - Auto face annotation, which aims to detect human faces from a facial image and
      assign them proper human names, is a fundamental research problem and beneficial
      to many real-world applications. In this work, we address this problem by
      investigating a retrieval-based annotation scheme of mining massive web facial
      images that are freely available over the Internet. In particular, given a facial
      image, we first retrieve the top $(n)$ similar instances from a large-scale web
      facial image database using content-based image retrieval techniques, and then
      use their labels for auto annotation. Such a scheme has two major challenges: 1)
      how to retrieve the similar facial images that truly match the query, and 2) how
      to exploit the noisy labels of the top similar facial images, which may be
      incorrect or incomplete due to the nature of web images. In this paper, we
      propose an effective Weak Label Regularized Local Coordinate Coding (WLRLCC)
      technique, which exploits the principle of local coordinate coding by learning
      sparse features, and employs the idea of graph-based weak label regularization to
      enhance the weak labels of the similar facial images. An efficient optimization
      algorithm is proposed to solve the WLRLCC problem. Moreover, an effective sparse
      reconstruction scheme is developed to perform the face annotation task. We
      conduct extensive empirical studies on several web facial image databases to
      evaluate the proposed WLRLCC algorithm from different aspects. The experimental
      results validate its efficacy. We share the two constructed databases "WDB"
      (714,454 images of 6,025 people) and "ADB" (126,070 images of 1,200 people) with
      the public. To further improve the efficiency and scalability, we also propose an
      offline approximation scheme (AWLRLCC) which generally maintains comparable
      results but significantly reduces the annotation time.

PMID- 24457511
TI  - Scene particles: unregularized particle-based scene flow estimation.
AB  - In this paper, an algorithm is presented for estimating scene flow, which is a
      richer, 3D analog of optical flow. The approach operates orders of magnitude
      faster than alternative techniques and is well suited to further performance
      gains through parallelized implementation. The algorithm employs multiple
      hypotheses to deal with motion ambiguities, rather than the traditional
      smoothness constraints, removing oversmoothing errors and providing significant
      performance improvements on benchmark data, over the previous state of the art.
      The approach is flexible and capable of operating with any combination of
      appearance and/or depth sensors, in any setup, simultaneously estimating the
      structure and motion if necessary. Additionally, the algorithm propagates
      information over time to resolve ambiguities, rather than performing an isolated
      estimation at each frame, as in contemporary approaches. Approaches to smoothing
      the motion field without sacrificing the benefits of multiple hypotheses are
      explored, and a probabilistic approach to occlusion estimation is demonstrated,
      leading to 10 and 15 percent improved performance, respectively. Finally, a data
      driven tracking approach is described, and used to estimate the 3D trajectories
      of hands during sign language, without the need to model complex appearance
      variations at each viewpoint.

PMID- 24457512
TI  - Simultaneous tensor decomposition and completion using factor priors.
AB  - The success of research on matrix completion is evident in a variety of real
      world applications. Tensor completion, which is a high-order extension of matrix
      completion, has also generated a great deal of research interest in recent years.
      Given a tensor with incomplete entries, existing methods use either factorization
      or completion schemes to recover the missing parts. However, as the number of
      missing entries increases, factorization schemes may overfit the model because of
      incorrectly predefined ranks, while completion schemes may fail to interpret the
      model factors. In this paper, we introduce a novel concept: complete the missing
      entries and simultaneously capture the underlying model structure. To this end,
      we propose a method called simultaneous tensor decomposition and completion
      (STDC) that combines a rank minimization technique with Tucker model
      decomposition. Moreover, as the model structure is implicitly included in the
      Tucker model, we use factor priors, which are usually known a priori in real
      world tensor objects, to characterize the underlying joint-manifold drawn from
      the model factors. By exploiting this auxiliary information, our method leverages
      two classic schemes and accurately estimates the model factors and missing
      entries. We conducted experiments to empirically verify the convergence of our
      algorithm on synthetic data and evaluate its effectiveness on various kinds of
      real-world data. The results demonstrate the efficacy of the proposed method and
      its potential usage in tensor-based applications. It also outperforms state-of
      the-art methods on multilinear model analysis and visual data completion tasks.

PMID- 24457513
TI  - Tensor sparse coding for positive definite matrices.
AB  - In recent years, there has been extensive research on sparse representation of
      vector-valued signals. In the matrix case, the data points are merely vectorized
      and treated as vectors thereafter (for example, image patches). However, this
      approach cannot be used for all matrices, as it may destroy the inherent
      structure of the data. Symmetric positive definite (SPD) matrices constitute one
      such class of signals, where their implicit structure of positive eigenvalues is
      lost upon vectorization. This paper proposes a novel sparse coding technique for
      positive definite matrices, which respects the structure of the Riemannian
      manifold and preserves the positivity of their eigenvalues, without resorting to
      vectorization. Synthetic and real-world computer vision experiments with region
      covariance descriptors demonstrate the need for and the applicability of the new
      sparse coding model. This work serves to bridge the gap between the sparse
      modeling paradigm and the space of positive definite matrices. 

PMID- 24457514
TI  - Variational light field analysis for disparity estimation and super-resolution.
AB  - We develop a continuous framework for the analysis of 4D light fields, and
      describe novel variational methods for disparity reconstruction as well as
      spatial and angular super-resolution. Disparity maps are estimated locally using
      epipolar plane image analysis without the need for expensive matching cost
      minimization. The method works fast and with inherent subpixel accuracy since no
      discretization of the disparity space is necessary. In a variational framework,
      we employ the disparity maps to generate super-resolved novel views of a scene,
      which corresponds to increasing the sampling rate of the 4D light field in
      spatial as well as angular direction. In contrast to previous work, we formulate
      the problem of view synthesis as a continuous inverse problem, which allows us to
      correctly take into account foreshortening effects caused by scene geometry
      transformations. All optimization problems are solved with state-of-the-art
      convex relaxation techniques. We test our algorithms on a number of real-world
      examples as well as our new benchmark data set for light fields, and compare
      results to a multiview stereo method. The proposed method is both faster as well
      as more accurate. Data sets and source code are provided online for additional
      evaluation. 

PMID- 24457516
TI  - Crosstalk between kinases and Nedd4 family ubiquitin ligases.
AB  - A dazzling array of human biological processes achieves coordination and balance
      through the posttranslational modification of protein residues with phosphate (95
      Da) or ubiquitin (8565 Da). Over the past years, a reciprocal communication has
      become recognized between phosphorylating (kinases) and ubiquitinating (E3
      ligases) enzymes. Such crosstalk occurs when a kinase acts on a ligase or vice
      versa to modify the catalytic activity, substrate specificity, or subcellular
      localization of the modified enzyme. In this review, we focus on the crosstalk
      between the nine members of the Nedd4 family E3 ubiquitin ligases with kinase
      signal transducers such as cell surface receptors, cytosolic kinases,
      phosphatases, and transcription factors. Since protein kinases are well explored
      and established therapeutic targets, we hypothesize that mapping E3 ligases onto
      kinase signalling networks will provide clues to the full therapeutic potential
      of pharmacologically targeting E3 ligases. 

PMID- 24457515
TI  - A highly selective fluorescent probe for cadmium ions in aqueous solution and
      living cells.
AB  - An organic salt based on double 1,3,4-oxadiazole derivatives as fluorophores and
      BAPTA as a receptor has been designed for detection of Cd(2+). The fluorescent
      probe exhibits high selectivity for Cd(2+) and a low detection limit of 20 nM in
      aqueous solution, making it useful for Cd(2+) imaging in living MCF-7 cells. 

PMID- 24457517
TI  - Identification of reference genes for qRT-PCR in human lung squamous-cell
      carcinoma by RNA-Seq.
AB  - Although the accuracy of quantitative real-time polymerase chain reaction (qRT
      PCR) is highly dependent on the reliable reference genes, many commonly used
      reference genes are not stably expressed and as such are not suitable for
      quantification and normalization of qRT-PCR data. The aim of this study was to
      identify novel reliable reference genes in lung squamous-cell carcinoma. We used
      RNA sequencing (RNA-Seq) to survey the whole genome expression in 5 lung normal
      samples and 44 lung squamous-cell carcinoma samples. We evaluated the expression
      profiles of 15 commonly used reference genes and identified five additional
      candidate reference genes. To validate the RNA-Seq dataset, we used qRT-PCR to
      verify the expression levels of these 20 genes in a separate set of 100 pairs of
      normal lung tissue and lung squamous-cell carcinoma samples, and then analyzed
      these results using geNorm and NormFinder. With respect to 14 of the 15 common
      reference genes (B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A, PPIA, RPLP0,
      TBP, TFRC, UBC, and YWHAZ), the expression levels were either too low to be
      easily detected, or exhibited a high degree of variability either between lung
      normal and squamous-cell carcinoma samples, or even among samples of the same
      tissue type. In contrast, 1 of the 15 common reference genes (ACTB) and the 5
      additional candidate reference genes (EEF1A1, FAU, RPS9, RPS11, and RPS14) were
      stably and constitutively expressed at high levels in all the samples tested.
      ACTB, EEF1A1, FAU, RPS9, RPS11, and RPS14 are ideal reference genes for qRT-PCR
      analysis of lung squamous-cell carcinoma, while 14 commonly used qRT-PCR
      reference genes are less appropriate in this context. 

PMID- 24457518
TI  - Sirt2 induces C2C12 myoblasts proliferation by activation of the ERK1/2 pathway.

PMID- 24457519
TI  - Dynamics of electrochemical lithiation/delithiation of graphene-encapsulated
      silicon nanoparticles studied by in-situ TEM.
AB  - The incorporation of nanostructured carbon has been recently reported as an
      effective approach to improve the cycling stability when Si is used as high
      capacity anodes for the next generation Li-ion battery. However, the mechanism of
      such notable improvement remains unclear. Herein, we report in-situ transmission
      electron microscopy (TEM) studies to directly observe the dynamic electrochemical
      lithiation/delithiation processes of crumpled graphene-encapsulated Si
      nanoparticles to understand their physical and chemical transformations.
      Unexpectedly, in the first lithiation process, crystalline Si nanoparticles
      undergo an isotropic to anisotropic transition, which is not observed in pure
      crystalline and amorphous Si nanoparticles. Such a surprising phenomenon arises
      from the uniformly distributed localized voltage around the Si nanoparticles due
      to the highly conductive graphene sheets. It is observed that the intimate
      contact between graphene and Si is maintained during volume
      expansion/contraction. Electrochemical sintering process where small Si
      nanoparticles react and merge together to form large agglomerates following
      spikes in localized electric current is another problem for batteries. In-situ
      TEM shows that graphene sheets help maintain the capacity even in the course of
      electrochemical sintering. Such in-situ TEM observations provide valuable
      phenomenological insights into electrochemical phenomena, which may help optimize
      the configuration for further improved performance. 

PMID- 24457520
TI  - Where exactly am I? Self-location judgements distribute between head and torso.
AB  - I am clearly located where my body is located. But is there one particular place
      inside my body where I am? Recent results have provided apparently contradictory
      findings about this question. Here, we addressed this issue using a more direct
      approach than has been used in previous studies. Using a simple pointing task, we
      asked participants to point directly at themselves, either by manual manipulation
      of the pointer whilst blindfolded or by visually discerning when the pointer was
      in the correct position. Self-location judgements in haptic and visual modalities
      were highly similar, and were clearly modulated by the starting location of the
      pointer. Participants most frequently chose to point to one of two likely
      regions, the upper face or the upper torso, according to which they reached
      first. These results suggest that while the experienced self is not spread out
      homogeneously across the entire body, nor is it localised in any single point.
      Rather, two distinct regions, the upper face and upper torso, appear to be judged
      as where "I" am. 

PMID- 24457521
TI  - Patients' understanding of how genotype variation affects benefits of tamoxifen
      therapy for breast cancer.
AB  - BACKGROUND: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and
      potentially a key determinant in breast cancer outcomes. Our study examined
      patients' beliefs about how the CYP2D6 genotype would affect their prognoses.
      METHODS: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for
      prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM =
      extensive, IM = intermediate, PM = poor metabolizing alleles). The informed
      consent said that the purpose of the trial was to examine effects of dose
      adjustment based on genotype, but that clinical benefits were uncertain. Our
      embedded sub-study surveyed 320 patients prior to receiving their genotypes. We
      experimentally manipulated 6 vignettes to describe hypothetical tamoxifen
      treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each
      vignette, women gave their perceived recurrence risk (RR; 0-100%). RESULTS: Women
      believed that genotype would not affect their RR if they did not take tamoxifen
      (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would
      affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). CONCLUSION:
      Women believed that extensive tamoxifen metabolizers had better prognoses,
      despite study materials stating uncertainty about any benefit. The rapidly
      changing nature of genomic science calls for caution when communicating clinical
      utility.

PMID- 24457523
TI  - Amygdalar disconnectivity could underlie stress resilience in the Ahi1 knockout
      mouse: conclusions from a resting-state functional MRI study.

PMID- 24457522
TI  - DISC1 as a genetic risk factor for schizophrenia and related major mental
      illness: response to Sullivan.

PMID- 24457524
TI  - On the interpretation of domain averaged Fermi hole analyses of correlated
      wavefunctions.
AB  - Few methods allow for a physically sound analysis of chemical bonds in cases
      where electron correlation may be a relevant factor. The domain averaged Fermi
      hole (DAFH) analysis, a tool firstly proposed by Robert Ponec in the 1990's to
      provide interpretations of the chemical bonding existing between two fragments
      Omega and Omega' that divide the real space exhaustively, is one of them. This
      method allows for a partition of the delocalization index or bond order between
      Omega and Omega' into one electron contributions, but the chemical interpretation
      of its parameters has been firmly established only for single determinant
      wavefunctions. In this paper we report a general interpretation based on the
      concept of excluded density that is also valid for correlated descriptions. Both
      analytical models and actual computations on a set of simple molecules (H2, N2,
      LiH, and CO) are discussed, and a classification of the possible DAFH situations
      is presented. Our results show that this kind of analysis may reveal several
      correlated assisted bonding patterns that might be difficult to detect using
      other methods. In agreement with previous knowledge, we find that the effective
      bond order in covalent links decreases due to localization of electrons driven by
      Coulomb correlation. 

PMID- 24457525
TI  - Terahertz imaging with sub-wavelength resolution by femtosecond laser filament in
      air.
AB  - Terahertz (THz) imaging provides cutting edge technique in biology, medical
      sciences and non-destructive evaluation. However, due to the long wavelength of
      the THz wave, the obtained resolution of THz imaging is normally a few hundred
      microns and is much lower than that of the traditional optical imaging. We
      introduce a sub-wavelength resolution THz imaging technique which uses the THz
      radiation generated by a femtosecond laser filament in air as the probe. This
      method is based on the fact that the femtosecond laser filament forms a waveguide
      for the THz wave in air. The diameter of the THz beam, which propagates inside
      the filament, varies from 20 MUm to 50 MUm, which is significantly smaller than
      the wavelength of the THz wave. Using this highly spatially confined THz beam as
      the probe, THz imaging with resolution as high as 20 MUm (~lambda/38 at 0.4 THz)
      can be realized. 

PMID- 24457526
TI  - Maternal vitamin D status and the risk of mild and severe preeclampsia.
AB  - BACKGROUND: We sought to determine the association between maternal vitamin D
      status at <=26 weeks' gestation and the risk of preeclampsia by clinical subtype.
      METHODS: We conducted a case-cohort study among women enrolled at 12 US sites
      from 1959 to 1966 in the Collaborative Perinatal Project. In serum collected at
      <=26 weeks' gestation (median 20.9 weeks) from 717 women who later developed
      preeclampsia (560 mild and 157 severe cases) and from 2986 mothers without
      preeclampsia, we measured serum 25-hydroxyvitamin D, over 40 years later, using
      liquid chromatography-tandem mass spectrometry. RESULTS: Half of women in the
      subcohort had 25-hydroxyvitamin D (25(OH)D) >50 nmol/L. Maternal 25(OH)D 50 to
      74.9 nmol/L was associated with a reduction in the absolute and relative risk of
      preeclampsia and mild preeclampsia compared with 25(OH)D <30 nmol/L in the crude
      analysis but not after adjustment for confounders, including race, prepregnancy
      body mass index, and parity. For severe preeclampsia, 25(OH)D >=50 nmol/L was
      associated with a reduction in three cases per 1000 pregnancies (adjusted risk
      difference = -0.003 [95% confidence interval = -0.005 to 0.0002]) and a 40%
      reduction in risk (0.65 [0.43 to 0.98]) compared with 25(OH)D <50 nmol/L.
      Conclusions were unchanged (1) after restricting to women with 25(OH)D measured
      before 22 weeks' gestation or (2) with formal sensitivity analyses for unmeasured
      confounding. CONCLUSIONS: Maternal vitamin D deficiency may be a risk factor for
      severe preeclampsia but not for its mild subtypes. Contemporary cohorts with
      large numbers of severe preeclampsia cases would be needed to confirm or refute
      these findings.

PMID- 24457527
TI  - Aerobic exercise attenuates the loss of skeletal muscle during energy restriction
      in adults with visceral adiposity.
AB  - OBJECTIVE: To evaluate the effects of energy restriction with or without aerobic
      exercise on thigh muscle mass and quality in adults with visceral adiposity.
      METHODS: 75 males and females were randomly assigned to the groups 'diet only'
      (DO; n = 42) or 'diet plus aerobic exercise' (D/Ex; n = 33) for 12 weeks. The
      target energy intake in both groups was 25 kcal/kg of ideal body weight. Subjects
      in the D/Ex group were instructed to exercise for >=300 min/week at lactate
      threshold. Computed tomography was used to measure thigh muscle cross-sectional
      area (CSA), normal-density muscle area (NDMA), and visceral fat area. RESULTS:
      Total body weight (DO: -6.6 +/- 3.6%; D/Ex: -7.3 +/- 4.6%) and visceral fat (DO: 
      16.0 +/- 13.8%; D/Ex: -23.1 +/- 14.7%) decreased significantly in both groups;
      however, the changes were not significantly different between the two groups. The
      decrease in muscle CSA was significantly greater in the DO group (-5.1 +/- 4.5%)
      compared with the D/Ex group (-2.5 +/- 5.0%). NDMA decreased significantly in the
      DO (-4.9 +/- 4.9%) but not in the D/Ex group (-1.4 +/- 5.0%). CONCLUSION: Aerobic
      exercise attenuated the loss of skeletal muscle during energy restriction in
      adults with visceral adiposity.

PMID- 24457528
TI  - Serum profiling of healthy aging identifies phospho- and sphingolipid species as
      markers of human longevity.
AB  - As centenarians well represent the model of healthy aging, there are many
      important implications in revealing the underlying molecular mechanisms behind
      such successful aging. By combining NMR metabonomics and shot-gun lipidomics in
      serum we analyzed metabolome and lipidome composition of a group of centenarians
      with respect to elderly individuals. Specifically, NMR metabonomics profiling of
      serum revealed that centenarians are characterized by a metabolic phenotype
      distinct from that of elderly subjects, in particular regarding amino acids and
      lipid species. Shot- gun lipidomics approach displays unique changes in lipids
      biosynthesis in centenarians, with 41 differently abundant lipid species with
      respect to elderly subjects. These findings reveal phospho/sphingolipids as
      putative markers and biological modulators of healthy aging, in humans.
      Considering the particular actions of these metabolites, these data are
      suggestive of a better counteractive antioxidant capacity and a well-developed
      membrane lipid remodelling process in the healthy aging phenotype. 

PMID- 24457529
TI  - Dietary herb extract rikkunshi-to ameliorates gastroparesis in Parkinson's
      disease: a pilot study.
AB  - OBJECTIVE: To perform an open trial on the effects of the extract of the dietary
      herb Rikkunshi-to (RKT) on gastroparesis in Parkinson's disease (PD) patients,
      using objective parameters given by the (13)C-sodium acetate expiration breath
      test (gastric emptying study). METHODS: Twenty patients with PD were enrolled
      into this study. Eleven patients were male and 9 were female, with the following
      characteristics (mean +/- SD): age, 69.4 +/- 8.17 years; disease duration, 4.34
      +/- 4.03 years; modified Hoehn and Yahr stage, 2.37 +/- 0.98, and Unified
      Parkinson's Disease Rating Scale Part 3 motor score, 16.6 +/- 7.37. Fourteen
      patients came to the clinic due to constipation; 16 patients were taking 288 +/-
      72 mg/day levodopa/carbidopa, 2 were taking dopamine agonists, and the others
      were not treated yet. All patients underwent the breath test. Statistical
      analysis was performed using Student's t test. RESULTS: RKT was well tolerated by
      all patients and none experienced abdominal pain or other adverse effects, except
      for its bitter taste. RKT significantly reduced the peak time of the (13)C-dose
      excess curve (p < 0.05). CONCLUSION: In this pilot trial, we found a significant
      shortening of the gastric emptying time after administration of the dietary herb
      extract RKT in PD patients. Further studies examining both gastric emptying and
      delayed-on in PD are warranted. .

PMID- 24457530
TI  - Creating functional engineered variants of the single-module non-ribosomal
      peptide synthetase IndC by T domain exchange.
AB  - Non-ribosomal peptide synthetases (NRPSs) are enzymes that catalyze ribosome
      independent production of small peptides, most of which are bioactive. NRPSs act
      as peptide assembly lines where individual, often interconnected modules each
      incorporate a specific amino acid into the nascent chain. The modules themselves
      consist of several domains that function in the activation, modification and
      condensation of the substrate. NRPSs are evidently modular, yet experimental
      proof of the ability to engineer desired permutations of domains and modules is
      still sought. Here, we use a synthetic-biology approach to create a small library
      of engineered NRPSs, in which the domain responsible for carrying the activated
      amino acid (T domain) is exchanged with natural or synthetic T domains. As a
      model system, we employ the single-module NRPS IndC from Photorhabdus luminescens
      that produces the blue pigment indigoidine. As chassis we use Escherichia coli.
      We demonstrate that heterologous T domain exchange is possible, even for T
      domains derived from different organisms. Interestingly, substitution of the
      native T domain with a synthetic one enhanced indigoidine production. Moreover,
      we show that selection of appropriate inter-domain linker regions is critical for
      functionality. Taken together, our results extend the engineering avenues for
      NRPSs, as they point out the possibility of combining domain sequences coming
      from different pathways, organisms or from conservation criteria. Moreover, our
      data suggest that NRPSs can be rationally engineered to control the level of
      production of the corresponding peptides. This could have important implications
      for industrial and medical applications.

PMID- 24457531
TI  - Mesoporous silica nanoparticles with redox-responsive surface linkers for charge
      reversible loading and release of short oligonucleotides.
AB  - Aimed at high loading and controlled release of oligonucleotides with short
      sequences of base-pairs, a novel series of mesoporous silica nanoparticles with
      three different pore sizes (3.5-5.0 nm) but the same cleavable surface linkers
      (MSN-Linker-Cys) were synthesized. The small particle size (~70 nm) with radially
      aligned pore structure and the well-defined surface linkers terminated with amino
      groups led to unprecedentedly high adsorption capacities of a model oligo DNA (21
      bp in length) into MSN-Linker-Cys particles, where MSN with a medium pore size of
      4.5 nm exhibited the highest adsorption capacity (190 mg g(-1)). The
      electrostatic attraction forces between amino groups on the surfaces and
      phosphate groups of DNA led to N/P ratios less than 1 in the particles, and
      retained the loaded DNA molecules inside the particles albeit with some degree of
      premature release observed. Triggered by the presence of reducing agents
      mimicking those found inside cells, the disulfide bond was shown to be cleaved in
      the organic linkers, generating a thiol group terminated surface. As a
      consequence, the most efficient release of DNA was found for MSN-Linker-Cys at
      neutral pH. A sustained responsive release with lower premature release ratio was
      obtained after a PEG polymer was conjugated to the free amines on the particle
      surface post adsorption of DNA. This nanocarrier design was based on the
      understanding and tuning of the molecular interactions between oligonucleotides
      and the cationic linkers. Thus, it is expected to lay the possibility for the
      development of innovative and strategic approaches for advancing related gene
      delivery technology. 

PMID- 24457532
TI  - Density and abundance of badger social groups in England and Wales in 2011-2013.
AB  - In the United Kingdom, European badgers Meles meles are a protected species and
      an important wildlife reservoir of bovine tuberculosis. We conducted a survey of
      badger dens (main setts) in 1614 1 km squares across England and Wales, between
      November 2011 and March 2013. Using main setts as a proxy for badger social
      groups, the estimated mean density of badger social groups in England and Wales
      was 0.485 km(-2) (95% confidence interval 0.449-0.521) and the estimated
      abundance of social groups was 71,600 (66,400-76,900). In the 25 years since the
      first survey in 1985-88, the annual rate of increase in the estimated number of
      badger social groups was 2.6% (2.2-2.9%), equating to an 88% (70-105%) increase
      across England and Wales. In England, we estimate there has been an increase of
      103% (83-123%) in badger social groups, while in Wales there has been little
      change (-25 to +49%).

PMID- 24457533
TI  - A Phase I Study of Tomotherapy in Patients With Primary Benign and Low-grade
      Brain Tumors: Late Toxicity and Quality of Life.
AB  - OBJECTIVES: To evaluate longitudinal quality of life and late neurotoxicity (>12
      mo) of tomotherapy in patients with primary benign and low-grade brain tumors.
      METHODS: Between January 2006 and October 2009, 49 patients with brain tumors
      were treated with tomotherapy at 2 radiotherapy centers in Canada. The median age
      of the patients was 51.0 years (range, 21 to 74 y); there were 21 men (42.86%)
      and 28 women (57.14%). All 49 patients had an initial Karnofsky performance score
      >=70. One patient (2.04%) received 45 Gy in 25 fractions, 27 patients (55.10%)
      received 50.4 Gy in 28 fractions, 15 patients (30.6%) received 54 Gy in 30
      fractions, and 5 patients (10.2%) received 60 Gy in 30 fractions. A total of 47
      patients were analyzed for late toxicity and outcomes. RESULTS: Changes in the
      Karnofsky Performance Status of the patients did not reach statistical
      significance (P>0.05). The majority of the quality of life parameters that
      reached a statistically significant level (P<0.05) of change at 2 years were
      changes toward improvement (drowsiness, itchy skin, emotional functioning,
      fatigue, nausea, and appetite). Statistically significant (P<0.05) interval
      deterioration in physical, role, and social functioning was observed. Actuarial
      overall survival at 5 years was 91.6%; disease-free survival at 5 years was
      86.6%. CONCLUSIONS: IMRT helical tomotherapy is well tolerated, without
      statistically significant constitutional and late neurotoxicity up to the 2-year
      mark.

PMID- 24457534
TI  - Stereotactic Body Radiation Therapy as Salvage for Intrathoracic Recurrence in
      Patients With Previously Irradiated Locally Advanced Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: The purpose of this study is to provide data on the outcomes of
      using stereotactic body radiotherapy (SBRT) as a means of salvage for non-small
      cell lung cancer (NSCLC) relapses previously treated with radiation. MATERIALS
      AND METHODS: The records of 128 consecutive patients treated with thoracic SBRT
      from 2009 through 2012 were retrospectively reviewed. Twenty-seven patients (29
      lesions) treated with prior thoracic radiation for stage IIB-IIIB NSCLC with
      subsequent recurrences and retreated with SBRT were identified. RESULTS: The
      median prior radiation dose was 64.8 Gy (range, 45 to 74 Gy) with a median
      retreatment dose of 50 Gy (range, 30 to 54 Gy), corresponding to a biological
      equivalent dose of 100 Gy (range, 48 to 151 Gy), at a median time of 13.4 months
      from prior radiation. The mean follow-up after salvage SBRT was 22 months. Local
      failure following salvage was 11%, nodal failure was 37%, and distant failure was
      30%. The local recurrence-free survival at 2 years was 72%. Out-of-field failure
      was predictive for worse local control (hazard ratio, 47.38; 95% confidence
      interval, 5.795-64.899). Progression-free survival at 1 year was 55% and 38% at 2
      years. Overall survival at 2 years from SBRT salvage was 79%. Salvage biological
      equivalent dose >=100 Gy was predictive of improved progression-free survival
      (48% vs. 18%, P=0.021) and overall survival (91% vs. 52%, P=0.004) at 2 years.
      The rate of symptomatic pneumonitis was 63% and chest wall pain reported was 26%.
      CONCLUSIONS: We observed improved outcomes following SBRT as a means of salvage
      for locally advanced recurrent NSCLC over traditional radiation therapy options.
      The toxicities were greater than expected from naive lung irradiation, but the
      adverse effects remained controlled with medications.

PMID- 24457535
TI  - Role of statin in atrial fibrillation-related stroke: an angiographic study for
      collateral flow.
AB  - BACKGROUND: Currently, intensive lipid lowering is recommended in patients with
      atherosclerotic ischemic stroke or transient ischemic attack. However, the role
      of statin in cardioembolic stroke is unclear. We investigated the association of
      statin with pretreatment collateral status in cardioembolic stroke. METHODS: A
      collaborative study from two stroke centers in distinct geographic regions
      included consecutive patients with acute middle cerebral artery (MCA) infarction
      due to atrial fibrillation (AF) who underwent cerebral angiography. The
      relationship between pretreatment collateral grade and the use/dose of statin at
      stroke onset was assessed. The angiographic collateral grade was evaluated
      according to the ASITN/SIR Collateral Flow Grading System. RESULTS: Ninety-eight
      patients (76 statin-naive, 22 statin users) were included. Compared with statin
      naive patients, statin users were older and more frequently had hypertension,
      hyperlipidemia and coronary heart disease. Excellent collaterals (grade 3-4) were
      more frequently observed in statin users (11 patients, 50%) than in statin-naive
      patients (21 patients, 27.6%; p = 0.049). The use of atorvastatin 10 mg
      equivalent or higher doses of statin was associated with excellent collaterals (p
      for trend = 0.025). In multiple regression analysis, prestroke statin use was
      independently associated with excellent collaterals (odds ratio, 7.841; 95%
      confidence interval, CI, 1.96-31.363; p = 0.004). CONCLUSIONS: Premorbid use of
      statin in AF patients is associated with excellent collateral flow. Although most
      statin trials excluded patients with cardioembolic stroke, our data suggests the
      possibility that statin may be beneficial in AF-related stroke

PMID- 24457536
TI  - Silicones as nonocclusive topical agents.
AB  - BACKGROUND/AIMS: Silicone excipients are commonly used ingredients because of
      their emollient and skin-conditioning effects, and their ability to form uniform,
      water-resistant, yet permeable films. Based on comparisons with organic materials
      and conflicting knowledge from silicones used in scar treatment, the
      misconception still exists that silicone topical excipients are occlusive
      substances that may block the passive loss of water through the upper skin
      layers. Therefore, 3 types of common silicone excipients and 3 water-in-(oil-plus
      silicone) or W/(O + Si) creams, containing 10% (w/w) of the respective silicones,
      were investigated as a function of time and compared to petrolatum. METHODS:
      Transepidermal water loss (TEWL) and skin hydration measurements were carried out
      after a single topical application on forearm skin of 26 healthy young female
      volunteers. RESULTS: Both petrolatum and silicones significantly decreased TEWL
      15 min after application, but the measurements for the silicones were not
      significantly different from the untreated control values. The tested silicones
      did not moisturize the skin. Petrolatum formed an occlusive layer, creating an
      increase in skin hydration for more than 4 h. The results measured for the W/(O +
      Si) creams indicated that they moisturized the skin, without any effect on TEWL.
      CONCLUSION: A clear difference was shown between the skin occlusive properties of
      petrolatum and the water vapor permeability of the common silicone excipient
      materials.

PMID- 24457537
TI  - Production of RNA for transcriptomic analysis from mouse spinal cord motor neuron
      cell bodies by laser capture microdissection.
AB  - Preparation of high-quality RNA from cells of interest is critical to precise and
      meaningful analysis of transcriptional differences among cell types or between
      the same cell type in health and disease or following pharmacologic treatments.
      In the spinal cord, such preparation from motor neurons, the target of interest
      in many neurologic and neurodegenerative diseases, is complicated by the fact
      that motor neurons represent <10% of the total cell population. Laser capture
      microdissection (LMD) has been developed to address this problem. Here, we
      describe a protocol to quickly recover, freeze, and section mouse spinal cord to
      avoid RNA damage by endogenous and exogenous RNases, followed by staining with
      Azure B in 70% ethanol to identify the motor neurons while keeping endogenous
      RNase inhibited. LMD is then used to capture the stained neurons directly into
      guanidine thiocyanate lysis buffer, maintaining RNA integrity. Standard
      techniques are used to recover the total RNA and measure its integrity. This
      material can then be used for downstream analysis of the transcripts by RNA-seq
      and qRT-PCR.

PMID- 24457538
TI  - Organosilicon platforms: bridging homogeneous, heterogeneous, and bioinspired
      catalysis.
AB  - Organosilicon compounds, in the form of cubic metallasiloxanes, cage-like
      silsesquioxanes, macromolecular nanocages, and flexible structures such as
      dendrimers and linear metallsiloxanes, have found useful applications as
      catalysts, ligands for metal complexes, and catalyst supports. Illustrative
      examples of these are presented. The well-defined structures of these compounds
      make them particularly suitable as molecular analogues of zeolites or silica
      supported catalysts. A unique feature of many of these compounds is the presence
      of flexible siloxane bonds, which accommodate large fluctuations in the framework
      geometry, reminiscent of the adaptability of enzymes to conformational changes,
      and distinguish siloxane containing materials from carbon based synthetic
      materials. New preparative pathways and the use of the versatile silyl ester as a
      protection group have greatly expanded synthetic possibilities, pointing to the
      possibility of assembling these structures to form multifunctional catalytic
      structures. Some nanocage structures, with functionalities organized in close
      proximity, exhibit nanoconfinement effects. 

PMID- 24457539
TI  - Controlling ferrofluid permeability across the blood-brain barrier model.
AB  - In the present study, an in vitro blood-brain barrier model was developed using
      murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain
      barrier model was completed by examining the permeability of FITCDextran at
      increasing exposure times up to 96 h in serum-free medium and comparing such
      values with values from the literature. After such confirmation, the permeability
      of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized
      using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen),
      GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB
      (collagen, PVA and BSA), was determined using this blood-brain barrier model. All
      of the five FF samples were characterized by zeta potential to determine their
      charge as well as TEM and dynamic light scattering for determining their
      hydrodynamic diameter. Results showed that FF coated with collagen passed more
      easily through the blood-brain barrier than FF coated with glycine and glutamic
      acid based on an increase of 4.5% in permeability. Through such experiments,
      diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use
      since they were less permeable to penetrate the blood-brain barrier to avoid
      neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more
      permeable to the blood-brain barrier (e.g. CPB).

PMID- 24457540
TI  - Compliance With Institutional Antimicrobial Dosing Guidelines in Patients
      Receiving Continuous Venovenous Hemodialysis.
AB  - OBJECTIVE: Describe the rate of compliance with institutional antimicrobial
      dosing guidelines in patients on concomitant continuous venovenous hemodialysis
      (CVVHD). METHODS: This single-center retrospective chart review evaluated adult
      patients receiving concomitant intravenous antimicrobials and CVVHD for at least
      24 hours over a 2-month period. RESULTS: A total of 42 patients, 76 antimicrobial
      courses, and 208 study days (24 hours of concomitant therapy) were evaluated.
      Overall, antimicrobials were dosed according to the institutional guidelines on
      162 (78%) of 208 study days. All nonconcordant doses were below recommendations.
      The recommended dose was never received prior to antibiotic or CVVHD
      discontinuation in 22% of the cases. In cases where antimicrobials were initiated
      when the patient was already on CVVHD, 74% of the initial doses met guideline
      criteria. Pharmacist recommendation was associated with increased dosing
      compliance (94% vs 73% of study days, P = .001). During transition from CVVHD to
      intermittent hemodialysis (IHD), only 62% of antimicrobial doses were decreased
      by the first IHD day. CONCLUSIONS: Antimicrobial dosing in patients on CVVHD was
      below institutional guideline recommendations in many cases. Pharmacist
      recommendation was associated with compliance. Centers should evaluate their own
      compliance rate with institutional guideline recommendations for CVVHD and
      implement initiatives to improve dosing practices.

PMID- 24457541
TI  - Lipopolysaccharide impaired the functional activity of endothelial colony-forming
      cells.
AB  - BACKGROUND: Recent studies have shown that endothelial progenitor cells (EPCs)
      contribute to lung repair after lipopolysaccharide (LPS)-induced lung injury and
      infusion of LPS decreased early EPCs in human peripheral blood. However, the
      effects of LPS on endothelial colony-forming cells (ECFCs) remain to be
      determined. OBJECTIVE: To investigate possible effects of LPS on the functional
      activity of ECFCs. METHODS: ECFCs were isolated from human umbilical cord blood
      and characterized. ECFCs at passages 3-5 were treated for 24 h with either LPS or
      vehicle control. Their viability, migration and in vitro vasculogenesis activity
      were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,
      modified Boyden chamber and in vitro angiogenesis assays, respectively. ECFC
      adhesion was assessed by replating cells on fibronectin-coated dishes and
      subsequent counting of adherent cells. RESULTS: Incubation with LPS dose
      dependently inhibited the viable, migratory, adhesive and in vitro vasculogenesis
      capacity of ECFCs. CONCLUSION: LPS impaired the functional activity of ECFCs.

PMID- 24457542
TI  - Macrolide/Azalide therapy for nodular/bronchiectatic mycobacterium avium complex
      lung disease.
AB  - BACKGROUND: There is no large study validating the appropriateness of current
      treatment guidelines for Mycobacterium avium complex (MAC) lung disease. This is
      a retrospective single-center review evaluating the efficacy of macrolide/azalide
      containing regimens for nodular/bronchiectatic (NB) MAC lung disease. METHODS:
      Patients were treated according to contemporary guidelines with evaluation of
      microbiologic responses. Macrolide susceptibility of MAC isolates was done at
      initiation of therapy, 6 to 12 months during therapy, and on the first
      microbiologic recurrence isolate. Microbiologic recurrence isolates also
      underwent genotyping for comparison with the original isolates. RESULTS: One
      hundred eighty patients completed > 12 months of macrolide/azalide multidrug
      therapy. Sputum conversion to culture negative occurred in 154 of 180 patients
      (86%). There were no differences in response between clarithromycin or
      azithromycin regimens. Treatment regimen modification occurred more frequently
      with daily (24 of 30 [80%]) vs intermittent (2 of 180 [1%]) therapy (P = .0001).
      No patient developed macrolide resistance during treatment. Microbiologic
      recurrences during therapy occurred in 14% of patients: 73% with reinfection MAC
      isolates, 27% with true relapse isolates (P = .03). Overall, treatment success
      (ie, sputum conversion without true microbiologic relapse) was achieved in 84% of
      patients. Microbiologic recurrences occurred in 74 of 155 patients (48%) after
      completion of therapy: 75% reinfection isolates, 25% true relapse isolates.
      CONCLUSIONS: Current guidelines for macrolide/azalide-based therapies for NB MAC
      lung disease result in favorable microbiologic outcomes for most patients without
      promotion of macrolide resistance. Intermittent therapy is effective and
      significantly better tolerated than daily therapy. Microbiologic recurrences
      during or after therapy are common and most often due to reinfection MAC
      genotypes.

PMID- 24457543
TI  - Understanding the emergence of the tobacco industry's use of the term tobacco
      harm reduction in order to inform public health policy.
AB  - OBJECTIVES: To explore the history of transnational tobacco companies' use of the
      term, approach to and perceived benefits of 'harm reduction'. METHODS: Analysis
      of internal tobacco industry documents, contemporary tobacco industry literature
      and 6 semistructured interviews. RESULTS: The 2001 Institute of Medicine report
      on tobacco harm reduction appears to have been pivotal in shaping industry
      discourse. Documents suggest British American Tobacco and Philip Morris
      International adopted the term 'harm reduction' from Institute of Medicine, then
      proceeded to heavily emphasise the term in their corporate messaging. Documents
      and interviews suggest harm reduction offered the tobacco industry two main
      benefits: an opportunity to (re-) establish dialogue with and access to policy
      makers, scientists and public health groups and to secure reputational benefits
      via an emerging corporate social responsibility agenda. CONCLUSIONS:
      Transnational tobacco companies' harm reduction discourse should be seen as
      opportunistic tactical adaptation to policy change rather than a genuine
      commitment to harm reduction. Care should be taken that this does not undermine
      gains hitherto secured in efforts to reduce the ability of the tobacco industry
      to inappropriately influence policy.

PMID- 24457544
TI  - Measuring long-lived 13C2 state lifetimes at natural abundance.
AB  - Long-lived disconnected eigenstates (for example, the singlet state in a system
      with two nearly equivalent carbons, or the singlet-singlet state in a system with
      two chemically equivalent carbons and two chemically equivalent hydrogens) hold
      the potential to drastically extend the lifetime of hyperpolarization in
      molecular tracers for in vivo magnetic resonance imaging (MRI). However, a first
      principles calculation of the expected lifetime (and thus selection of potential
      imaging agents) is made very difficult because of the large variety of relevant
      intra- and intermolecular relaxation mechanisms. As a result, all previous
      measurements relied on costly and time consuming syntheses of (13)C labeled
      compounds. Here we show that it is possible to determine (13)C singlet state
      lifetimes by detecting the naturally abundant doubly-labeled species. This
      approach allows for rapid and low cost screening of potential molecular
      biomarkers bearing long-lived states. 

PMID- 24457546
TI  - Latin American Collaborative Study of Congenital Malformations (ECLAMC): a model
      for health collaborative studies.

PMID- 24457547
TI  - Multichannel scanning probe microscopy and spectroscopy of graphene moire
      structures.
AB  - The graphene moire structures on 4d and 5d metals, as they demonstrate both long
      (moire) and short (atomic) scale ordered structures, are the ideal systems for
      the application of scanning probe methods. Taking graphene-Ir(111) as an example,
      we present the complex studies of this graphene-metal moire-structure system by
      means of 3D scanning tunnelling and atomic force microscopy/spectroscopy as well
      as Kelvin-probe force microscopy. The results clearly demonstrate variation of
      the moire and atomic scale contrast as a function of the bias voltage as well as
      the distance between the scanning probe and the sample, allowing one to
      discriminate between topographic and electronic contributions in the imaging of a
      graphene layer on metals. The presented results are compared with the state-of
      the-art density functional theory calculations demonstrating excellent agreement
      between theoretical and experimental data. 

PMID- 24457545
TI  - Complex self-assembly of pyrimido[4,5-d]pyrimidine nucleoside supramolecular
      structures.
AB  - Supramolecular self-assembly is not only one of the chemical roots of biological
      structure but is also drawing attention in different industrial fields. Here we
      study the mechanism of the formation of a complex flower-shaped supramolecular
      structure of pyrimido[4,5-d]pyrimidine nucleosides by dynamic light scattering,
      scanning electron microscopy, differential scanning calorimetry, nuclear magnetic
      resonance and X-ray analysis. Upon removing the hydroxyl group of sugars,
      different flower-shaped superstructures can be produced. These works demonstrate
      that complex self-assembly can indeed be attained through hierarchical non
      covalent interactions of single molecules. Furthermore, chimerical structures
      built from molecular recognition by these monomers indicate their potential in
      other fields if combined with other chemical entities. 

PMID- 24457549
TI  - Drugs for HIV infection.

PMID- 24457548
TI  - Validity of minimal clinically important difference values for the multiple
      sclerosis walking scale-12?
AB  - BACKGROUND AND OBJECTIVE: Minimal clinically important difference (MCID) values
      of 4 and 6 points have been proposed for interpreting meaningful change in
      Multiple Sclerosis Walking Scale-12 (MSWS-12) scores. This study examined the
      validity of those MCID values based on capturing corresponding changes in other
      walking outcomes in persons with multiple sclerosis (MS). METHODS: On 2 occasions
      separated by 6 months, 82 persons with MS completed the MSWS-12, timed 25-ft walk
      (T25FW), 6-min walk (6MW), and gait analysis, and then wore an accelerometer over
      a 7-day period. We generated change scores for the MSWS-12 and formed groups of
      stable, worsened, and improved perceived walking based on both 4- and 6-point
      changes. The groups were compared for corresponding changes in other walking
      measures over time using mixed-model ANOVAs. RESULTS: The mixed-model ANOVAs did
      not identify statistically significant group-by-time interactions on the T25FW (p
      = 0.98 and p = 0.67), the 6MW (p = 0.89 and p = 0.72), gait (p = 0.54 and p =
      0.21), or accelerometry (p = 0.40 and p = 0.68) for MCID values of 4- or 6-point
      changes in MSWS-12 scores. CONCLUSIONS: We did not confirm that MCID values of 4
      and 6 points for the MSWS-12 correspond with changes in performance, gait, and
      free-living assessments of walking in MS.

PMID- 24457550
TI  - As we come to the closing of our information on the past year, it is important to
      share with you our impressive growth in submissions. Introduction.

PMID- 24457551
TI  - RhoC mediates invasion and migration of CaSki cells through the Rho-associated
      serine-threonine protein kinase 1 signaling pathway.
AB  - OBJECTIVE: The small GTPase RhoC in human cancers is up-regulated and correlated
      with tumor metastasis. However, the role of Rho/Rho-associated serine-threonine
      protein kinase 1 (ROCK1) signaling pathway in human cervical cancer is still
      unclear. In this study, we examine the effects of RhoC and its major downstream
      target, ROCK1, on the invasion and migration of CaSki cells to investigate the
      role of RhoC/ROCK1 signaling pathway in the progression of cervical squamous cell
      carcinoma. METHODS: RhoC and ROCK1 protein expression in CaSki cells was detected
      by Western blotting. Scratch and transwell assays were carried out to assess the
      effects of RhoC on invasion and migration of CaSki cells. Cell viability was
      assayed by MTT test after adding the ROCK1 inhibitor Y-27632 to CaSki cells.
      RESULTS: Overexpression of RhoC protein in CaSki cells significantly increases
      ROCK1 expression and promotes cell invasion and migration compared with the
      control group (P < 0.05). However, in the inhibition of ROCK1 with Y-27632 in
      CaSki cells when RhoC was overexpressed, the rate of invasiveness and migration
      was reduced remarkably (P < 0.05), dropping to comparable levels as the control.
      CONCLUSIONS: This study suggested that the activation of RhoC/ROCK1 signaling
      pathways is likely involved in the progression of cervical squamous cell
      carcinoma.

PMID- 24457552
TI  - Secondary complete cytoreduction in recurrent ovarian cancer: benefit of optimal
      patient selection using scoring system.
AB  - OBJECTIVE: Complete tumor cytoreduction seems to be beneficial for patients with
      recurrent epithelial ovarian cancer (REOC). The challenge is to identify patients
      eligible for such surgery. Several scores based on simple clinical parameters
      have attempted to predict resectability and help in patient selection for surgery
      in REOC.The aims of this study were to assess the performance of these models in
      an independent population and to evaluate the impact of complete resection.
      MATERIALS AND METHODS: A total of 194 patients with REOC between January 2000 and
      December 2010 were included in 2 French centers. Two scores were used: the AGO
      DESKTOP OVAR trial score and a score from Tian et al.The performance
      (sensitivity, specificity, and predictive values) of these scores was evaluated
      in our population. Survival curves were constructed to evaluate the survival
      impact of surgery on recurrence. RESULTS: Positive predictive values for complete
      resection were 80.6% and 74.0% for the DESKTOP trial score and the Tian score,
      respectively. The false-negative rate was high for both models (65.4% and 71.4%,
      respectively). We found a significantly higher survival in the patients with
      complete resection (59.4 vs 17.9 months, P < 0.01) even after adjustment for the
      confounding variables (hazard ratio [HR], 2.53; 95% confidence interval, 1.01
      6.3; P = 0.04). CONCLUSIONS: In REOC, surgery seems to have a positive impact on
      survival, if complete surgery can be achieved. However, factors predicting
      complete resection are not yet clearly defined. Recurrence-free interval and
      initial resection seem to be the most relevant factors. Laparoscopic evaluation
      could help to clarify the indications for surgery.

PMID- 24457554
TI  - A highly emissive inorganic hexamolybdenum cluster complex as a handy precursor
      for the preparation of new luminescent materials.
AB  - The synthesis and characterisation of a new, highly luminescent inorganic cluster
      complex, (Bu4N)2[Mo6I8(NO3)6], are described. The complex possesses labile
      nitrato ligands and is therefore a useful precursor for the design of new
      luminescent materials. To exemplify this, functionalised polystyrene beads have
      been utilised as "polymeric ligands" to immobilise the molybdenum cluster
      complex. 

PMID- 24457553
TI  - Anxiolytic-like effects observed in rats exposed to the elevated zero-maze
      following treatment with 5-HT2/5-HT3/5-HT4 ligands.
AB  - The present study examined the effects of administering selective 5-HT
      antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of
      anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM)
      paradigm with respect to measuring anxiety, yet has been utilized less
      frequently. Three experiments were conducted each with a diazepam control (0.25,
      0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT2C
      antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT2C agonist MK-212 (0.25,
      0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT3
      antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT3 agonist SR 57227A (0.1, 1.0
      and 3.0 mg/kg), and in the third experiment, we administered the 5-HT4 antagonist
      RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT4 agonist RS 67333 (0.01, 0.1 and 0.5
      mg/kg). The administration of 5-HT2/3/4 subtype antagonists all generated
      behavioral profiles indicative of anxiolytic-like effects in the EZM, which was
      apparent from examination of both traditional and ethological measures. While
      little effect was observed from 5-HT2 and 5-HT3 agonists, the 5-HT4 agonist RS
      67333 was found to produce a paradoxical anxiolytic-like effect similar to that
      produced by the 5-HT4 antagonist RS 39604. We conclude by discussing the
      implications of these findings. 

PMID- 24457555
TI  - 2,4-Dihydroxypyrimidine is a potential urinary metabolite biomarker for
      diagnosing bipolar disorder.
AB  - Bipolar disorder (BD) is a common and debilitating mental disorder. However,
      there are no biomarkers available to aid in the diagnosis of this disorder. Here,
      we used a gas chromatography-mass spectrometry (GC-MS) based metabonomic method
      to characterize the urinary metabolic profiling of BD subjects and healthy
      controls to identify and validate urinary metabolite biomarkers for BD.
      Multivariate statistical analysis was used to visualize group discrimination and
      identify differentially expressed urinary metabolites in BD subjects relative to
      the healthy controls. Multivariate statistical analysis showed that the BD group
      was significantly distinguishable from the healthy control. Totally, 37 urinary
      metabolites responsible for discriminating BD subjects from healthy controls were
      identified. Interestingly, of 37 differential metabolites, 2,4
      dihydroxypyrimidine was identified as an effective diagnostic biomarker for BD,
      yielding an area under the receiver operating characteristic curve (AUC) of 0.889
      in the training samples (45 BD subjects and 61 healthy controls) and 0.805 in the
      test samples (26 BD subjects and 33 healthy controls). Our findings suggest that
      2,4-dihydroxypyrimidine is a promising candidate urinary biomarker for BD, which
      may facilitate development of a urine-based diagnostic test for BD. 

PMID- 24457556
TI  - AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine.
AB  - Activation-induced cytidine deaminase (AID) was originally identified as an
      inducer of somatic hypermutation (SHM) and class switch recombination (CSR) in
      immunoglobulin genes. However, AID can also cause mutations in host genes and
      contribute to cancer progression and drug resistance. In this study, molecular
      docking showed the interaction of free 5-aza-CdR and Zebularine (Zeb) with AID.
      However, only 5-aza-CdR-incorporated ssDNA bound to the active site of AID and
      inhibited AID expression through proteasomal degradation. 5-aza-CdR demonstrated
      cytotoxicity against AID-positive and -negative hematopoietic cancer cells. In
      contrast, Zeb exhibited a cytotoxic effect only in AID-negative cells due to its
      inability to inhibit AID expression. This differential effect might be due to the
      DNMT1 stabilization induced by AID, thus restricting the ability of Zeb to
      deplete DNMT1 and induce tumor suppressor genes (TSGs), such as p21, in AID
      positive cells. Moreover, the in vivo anticancer effect of 5-aza-CdR but not Zeb
      in AID-positive hematopoietic cancer cells was demonstrated. The study not only
      displays the association of AID and DNMT1 and identifies a novel biological
      function of AID, but also provides novel information regarding the use of DNMT
      inhibitors to treat AID-positive hematopoietic cancers. 

PMID- 24457559
TI  - The diversity of friction behavior between  bi-layer graphenes.
AB  - For relative sliding between two rigid graphene sheets that are interacted on by
      a van der Waals force, we show that the friction behavior is significantly
      dependent on the interlayer separation distance h. Around the equilibrium
      interlayer distance he, the friction behavior exactly obeys a linear law. When h
      is far smaller than he, the linear friction behavior transforms to overlinear
      behavior. On the other hand, when h is larger than he, there is another critical
      value of the interlayer distance, hc; when h is larger than he and smaller than
      hc, the friction behavior transforms from linear to sublinear behavior; however,
      when h is larger than hc, the coefficient of friction becomes negative. Further,
      the different friction behaviors are found to be well described by a universal
      power law, tau = MU*(sigma + sigma0)(n).

PMID- 24457558
TI  - A facile process for soak-and-peel delamination of CVD graphene from substrates
      using water.
AB  - We demonstrate a simple technique to transfer chemical vapour deposited (CVD)
      graphene from copper and platinum substrates using a soak-and-peel delamination
      technique utilizing only hot deionized water. The lack of chemical etchants
      results in cleaner CVD graphene films minimizing unintentional doping, as
      confirmed by Raman and electrical measurements. The process allows the reuse of
      substrates and hence can enable the use of oriented substrates for growth of
      higher quality graphene, and is an inherently inexpensive and scalable process
      for large-area production. 

PMID- 24457557
TI  - Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed
      enzyme prodrug therapy.
AB  - The pre-clinical and clinical development of viral vehicles for gene transfer
      increased in recent years, and a recombinant adeno-associated virus (rAAV) drug
      took center stage upon approval in the European Union. However, lack of
      standardization, inefficient purification methods and complicated retargeting
      limit general usability. We address these obstacles by fusing rAAV-2 capsids with
      two modular targeting molecules (DARPin or Affibody) specific for a cancer cell
      surface marker (EGFR) while simultaneously including an affinity tag (His-tag) in
      a surface-exposed loop. Equipping these particles with genes coding for prodrug
      converting enzymes (thymidine kinase or cytosine deaminase) we demonstrate tumor
      marker specific transduction and prodrug-dependent apoptosis of cancer cells.
      Coding terminal and loop modifications in one gene enabled specific and scalable
      purification. Our genetic parts for viral production adhere to a standardized
      cloning strategy facilitating rapid prototyping of virus directed enzyme prodrug
      therapy (VDEPT). 

PMID- 24457560
TI  - Antiviral drugs for influenza 2013-2014.

PMID- 24457561
TI  - In brief: ponatinib (Inclusig) returns.

PMID- 24457562
TI  - Sofosbuvir (Sovaldi) for chronic hepatitis C.

PMID- 24457563
TI  - Fabrication of uniform nanoscale cavities via silicon direct wafer bonding.
AB  - Measurements of the heat capacity and superfluid fraction of confined (4)He have
      been performed near the lambda transition using lithographically patterned and
      bonded silicon wafers. Unlike confinements in porous materials often used for
      these types of experiments(3), bonded wafers provide predesigned uniform spaces
      for confinement. The geometry of each cell is well known, which removes a large
      source of ambiguity in the interpretation of data. Exceptionally flat, 5 cm
      diameter, 375 um thick Si wafers with about 1 um variation over the entire wafer
      can be obtained commercially (from Semiconductor Processing Company, for
      example). Thermal oxide is grown on the wafers to define the confinement
      dimension in the z-direction. A pattern is then etched in the oxide using
      lithographic techniques so as to create a desired enclosure upon bonding. A hole
      is drilled in one of the wafers (the top) to allow for the introduction of the
      liquid to be measured. The wafers are cleaned(2) in RCA solutions and then put in
      a microclean chamber where they are rinsed with deionized water(4). The wafers
      are bonded at RT and then annealed at ~1,100  degrees C. This forms a strong and
      permanent bond. This process can be used to make uniform enclosures for measuring
      thermal and hydrodynamic properties of confined liquids from the nanometer to the
      micrometer scale. 

PMID- 24457564
TI  - The effect of germ-line BRCA mutations on response to chemotherapy and outcome of
      recurrent ovarian cancer.
AB  - OBJECTIVE: The treatment of recurrent epithelial ovarian cancer (rEOC) remains a
      major challenge because of the development of platinum resistance. To identify
      treatment regimens associated with better outcomes in BRCA mutation carriers
      compared with patients with nonhereditary (NH) disease, we summarized the
      experience after chemotherapy treatment of rEOC in 1 institution and compared the
      outcome in BRCA mutation carriers versus NH subsets. METHODS: We retrospectively
      analyzed 256 patient records with rEOC who were treated with second-, third-, and
      fourth-line treatment with the usual sequential regimens consisting of either
      pegylated liposomal doxorubicin (PLD), taxanes, gemcitabine, or topotecan (alone
      or in combination with platinum) between 2002 and 2012 at our institution. The
      analysis of founder mutations in 8 hotspots was performed. The outcome in BRCA
      mutation carriers was compared with that of patients with NH disease. RESULTS:
      BRCA mutation carriers treated with PLD (with or without platinum) or with
      gemcitabine + platinum had improved progression-free survival (PFS) and a lower
      risk for disease progression (adjusted for age, line of treatment, and platinum
      sensitivity) compared with patients with NH disease. By contrast, treatment with
      taxanes (with or without platinum) or topotecan led to similar PFS in BRCA
      mutation carriers and in patients with NH disease. Under all treatment regimens,
      BRCA mutation carriers showed improved overall survival after adjusting for age,
      line of treatment, and platinum sensitivity. CONCLUSIONS: This single-institution
      experience provides indications of an enhanced benefit in PFS for BRCA mutation
      carriers compared with patients with NH disease across a number of drug regimens
      (PLD, platinum, or gemcitabine + platinum) regardless of platinum sensitivity and
      line of therapy.

PMID- 24457565
TI  - Obesity, metabolic syndrome and nutrition.

PMID- 24457566
TI  - Neonatal and infant nutrition, breastfeeding.

PMID- 24457567
TI  - Cognition.

PMID- 24457568
TI  - Nutrition and growth in chronic diseases.

PMID- 24457569
TI  - Malnutrition and catch-up growth during childhood and puberty.

PMID- 24457570
TI  - Pregnancy: impact of maternal nutrition on intrauterine fetal growth.

PMID- 24457571
TI  - World Review of Nutrition and Dietetics. Nutrition and growth. Preface.

PMID- 24457572
TI  - Safety and outcome of patients treated with a modified outpatient intraperitoneal
      regimen for epithelial ovarian, primary peritoneal or fallopian tube cancer.
AB  - BACKGROUND: Despite the survival benefit of intraperitoneal (IP) chemotherapy
      observed in GOG172, significant toxicity and poor treatment completion rates have
      prevented the widespread acceptance of this regimen. Here, we report our
      experience with a modified outpatient GOG172 regimen. METHODS: Eligible patients
      had stage III, optimally debulked epithelial ovarian, fallopian tube or primary
      peritoneal cancer that underwent IP port placement for administration of a
      modified GOG172 regimen consisting of: (i) intravenous paclitaxel 135 mg/m2 on
      day 1 over 3 h; (ii) intraperitoneal cisplatin 75 mg/m2 on day 2, and (iii)
      intraperitoneal paclitaxel 60 mg/m2 on day 8. Day 8 IP paclitaxel was omitted
      until tolerance of the first cycle of IP cisplatin had been established. RESULTS:
      Four or more cycles of IP chemotherapy were completed by 72.5% (29) of 40
      eligible patients; 20% of patients exhibited catheter-related complications
      requiring port removal and discontinuation of IP chemotherapy. Grade 3-4
      hematologic, metabolic and gastrointestinal toxicities occurred in 36, 8 and 21%
      of the patients, respectively. With a median follow-up of 47.7 months,
      progression-free and overall survival was comparable to GOG172. CONCLUSIONS: This
      modified outpatient GOG172 regimen is associated with less toxicity and improved
      completion rates compared to the original GOG172 regimen.

PMID- 24457573
TI  - Trap gun: an unusual firearm, aimed at wild animals but causing a silent epidemic
      of human fatalities.
AB  - Among a variety of uncommon firearms of different origin used worldwide, the trap
      gun used in Sri Lanka is underreported. This is an illegal, locally made, smooth
      bore, long-barreled, muzzle-loading firearm with a victim-activated simple
      trigger mechanism. It is mainly used to protect crops and livestock from the
      potential harm by wild animals. Trap gun is mounted horizontally on pegs of
      sticks fixed to the ground. Miscellaneous metal pieces are used as ammunition. A
      small metal container filled with powdered matchstick heads/firecrackers covered
      by the striker surface of the matchstick box is used as the percussion cap. A
      metal hammer is set to hit the percussion cap. Through a lever mechanism, the
      hammer is kept under tension. The lever mechanism is connected to a trigger cord,
      which runs across the animal path. The first passerby, a human being or a wild
      animal, who accidentally trips the trigger cord and activates the trigger
      mechanism is critically injured. This characteristically damages the lower limbs
      of the human being. This communication highlights a death due to trap gun injury.
      The injury pattern caused by trap gun could overlap with that of shotgun and
      rifled firearm. A meticulous autopsy could sort it out.

PMID- 24457574
TI  - Fatal corrosive attack: a study of 13 cases from central Delhi, India.
AB  - The present study is a retrospective analysis of 13 cases of deaths, which
      resulted from throwing of corrosives over the body. The cases were autopsied at
      the Department of Forensic Medicine, Maulana Azad Medical College & Associated
      Hospitals, Delhi, India, during a period of 13 years from July 1998 to June 2011.
      The cases represented approximately 0.1% of all autopsy cases during the same
      period. Data were analyzed with regard to the age, sex, place of occurrence,
      pattern of injury, survival period, and cause of death. Of these cases, 8
      (61.54%) were male, and 5 (38.46%) were female. The most common age group of the
      victim was 21 to 30 years (46.15%). Six of the victims were attacked on the road
      side. Face and thorax were involved in all cases (100%). The average total body
      surface area of burn was 56.69%.The mean survival period was 28.2 days. In 53.85%
      of cases, the cause of death was septicemia. 

PMID- 24457575
TI  - "Samosa" pneumoconiosis: a case of pulmonary talcosis uncovered during a
      medicolegal autopsy.
AB  - Talcosis is a rare form of pneumoconiosis caused by long-term exposure to talc
      (hydrous magnesium silicate) through inhalation or intravenous exposures.
      Although it occurs commonly as an occupational hazard or is due to abuse/overuse
      of talc, talcosis in the course of food adulteration is seldom or hardly
      reported. We present a case of talcosis in a worker who had considerable exposure
      to talc during the initial preparation of "samosa," a triangular fried Indian
      savory. There were typical pulmonary histological findings of talcosis with
      extensive deposition of birefringent crystals in histiocytes. On account of this
      unusual pathogenesis, we have coined a new terminology "samosa pneumoconiosis" to
      describe this condition. 

PMID- 24457576
TI  - Temperature measurement from the brain and rectum in charred corpses: a pilot
      study on an animal model.
AB  - Measurement of body temperature provides relevant data on postmortem interval,
      and different studies have been so far attempted to apply temperature assessment
      methods also under extreme environmental conditions; however, none of them has
      been performed yet on charred or heated bodies, where temperature measurement is
      presumed to be unreliable because of the possible influence of heating. This
      study aimed at verifying any possible early-stage alterations of rectal and
      endocranial temperature due to fire on an animal model during the charring
      process. Three pigs, 2 adults (pigs 1 and 2) whose weight was about 50 kg each
      and 1 piglet weighing 3 kg, were heated and burnt on a natural fire lit on top of
      a wooden stack, without the use of accelerants; 2 thermocouples were positioned
      in the rectum and in the cranium to record second-by-second rectal and
      endocranial temperature values. Results demonstrate that the rectal temperature
      does not seem to increase in adult pigs for 40 to 50 minutes after the body has
      been exposed to fire, probably because of the thermal insulating characteristics
      of the adipose tissue. Therefore, temperature may still be of some help for
      estimating postmortem interval on heated or burnt cadavers.

PMID- 24457577
TI  - A peculiar case of suicide enacted through the ancient Japanese ritual of Jigai.
AB  - In the past, self-infliction of sharp force was a classic form of suicide, while
      in modern times it is quite rare, constituting only 2% to 3% of all self
      inflicted deaths. In Japan, the jigai (Japanese characters: see text) ritual is a
      traditional method of female suicide, carried out by cutting the jugular vein
      using a knife called a tanto. The jigai ritual is the feminine counterpart of
      seppuku (well-known as harakiri), the ritual suicide of samurai warriors, which
      was carried out by a deep slash into the abdomen. In contrast to seppuku, jigai
      can be performed without assistance, which was fundamental for seppuku.The case
      we describe here involves an unusual case of suicide in which the victim was a
      male devotee of Japanese culture and weapons. He was found dead in his bathtub
      with a deep slash in the right lateral-cervical area, having cut only the
      internal jugular vein with a tanto knife, exactly as specified by the jigai
      ritual.

PMID- 24457578
TI  - Evaluation of shotgun suicides in Konya, Turkey between 2000 and 2007.
AB  - The number of the suicides is increasing all around the world. In this study, the
      cases autopsied between 2000 and 2007 in The Konya Branch of Forensic Medicine
      Council were retrospectively investigated. Fifty-seven shotgun suicides were
      determined. The cases were evaluated in terms of their demographic characters,
      site of entrance wound, the type of the cartridge used, shooting distance, the
      place of incident, the place of death, motive for suicide, and the presence of
      previous suicide attempts. The most preferred site of entrance wound was the head
      with 34 cases (59.7%). Of 34 cases in which the entrance wound was on the head,
      there was indirect mandibular fracture in 16 cases (47.1%). In 11 cases (19.3%),
      there observed small ecchymosed abrasions on the finger surfaces, which are
      thought to have resulted from the trigger kicking back during triggering or the
      finger having been stuck between the trigger and the trigger guard. It is
      concluded that there is a need for a legal regulation that makes obtaining of
      shotguns more difficult and the people who have them are to be educated not to
      keep them in easily accessible places. 

PMID- 24457579
TI  - Homicide by blunt trauma in Brescia county (northern Italy) between 1982 and
      2012.
AB  - Blunt force injuries are produced by a variety of objects, including hands and
      feet (which is human strength) and many different weapons. Some of these objects
      produce distinctive patterns of injury of potential evidentiary value. This
      article presents a series of 53 homicides by blunt trauma along the period from
      1982 to 2012, representing 16% of all homicides treated by the University
      Institute of Forensic Medicine in Brescia (northern Italy). Fifty-seven percent
      (30 cases) of the victims were male. The mean age of the victims was 47.9 years.
      The weapon most frequently involved was human strength. Not surprisingly, head
      trauma was the most common cause of death (66%). Forty-seven percent (25 cases)
      of the victims survived their assaults for varying periods. Homicides due to
      blunt trauma are still a relevant challenge for the forensic pathologist, who
      must obtain a complete and accurate history of the crime (including details
      regarding the crime scene), interpret patterns of injury and other findings at
      autopsy, and correlate all of the findings to make an accurate ruling of the
      cause and manner of death. 

PMID- 24457580
TI  - Fatal cardiac tamponade associated with central venous catheter: a report of 2
      cases diagnosed in autopsy.
AB  - The authors present 2 cases of fatal cardiac tamponade associated with the
      insertion of a central venous catheter. The first case occurred soon after the
      insertion of the catheter (early complication), and the second case, 4 days after
      (late complication). In both cases, the post-catheter insertion check chest x-ray
      film showed the tip of the catheter located within the heart silhouette. The
      diagnosis of cardiac tamponade was made only during the cadaverous examination.
      In the first case, the catheter was found to be in the right internal jugular
      vein at autopsy. The postmortem examination showed a clear liquid inside the
      pericardial cavity and the inferior vena cava injury. In the second case, the
      catheter had been inserted via the right subclavian vein puncture and there was a
      perforation of the right atrium at autopsy. The child was using total parenteral
      nutrition, and the intrapericardial liquid was milky. The incorrect placement of
      the catheter tip and unrecognized complications led the 2 children to death. 

PMID- 24457582
TI  - An unusual case of incaprettamento.
AB  - Incaprettamento is a ritual strangulation that represents a method of homicide
      typical of the Italian Mafia. While the victim is in the prone position, he/she
      is bound by one end of a rope, creating a slipknot around the throat, while the
      other end is used to tie the limbs behind the back. Forensic investigations
      reveal that in most cases, the binding of the extremities and the positioning of
      the victim are carried out after death due to others means and are intended to
      hold somebody in contempt and to punish betrayers. When the victim is tied while
      alive, the death is caused by self-strangulation because it is impossible to
      maintain the legs in this forced position. Here, we describe in detail a case
      with a lot of similarities to incaprettamento, although we define it as atypical
      because of the unusual methods of the actual binding and the circumstances in
      which death occurred. In fact, the investigation of the crime scene, the external
      and internal findings, and the histologic examination result show that this is a
      crime of passion. 

PMID- 24457581
TI  - A survey on spousal abuse of 500 victims in Iran.
AB  - Spousal abuse is a serious social problem, which includes a variety of physical,
      emotional, and sexual violence. Many studies conducted on this subject in
      different countries show that the actual severity of this problem is far greater
      than it seems at first glance. Because legal medical centers are the main places
      where victims are referred, 500 abused victims who were directed to these centers
      during 2012 were asked to fill out preplanned forms and the collected data were
      analyzed using analytic methods. The results showed that the average age of the
      women was 32 years, and their husbands' average age was 36 years. Most of the
      women had high school diplomas and they were living with their husbands and
      children. Most of the subjects were housekeepers and had married through their
      own choice and personal interest. In most of the cases, the initial instance of
      physical abuse occurred in the first year after marriage, and the head and face
      were the most frequently injured parts of their body. In a high percentage of
      cases, the partner was drunk, addicted, or had a history of mental illness. A
      significant relationship was found between alcohol and drug abuse with domestic
      violence in this study.

PMID- 24457583
TI  - Blood alcohol stability in postmortem blood samples.
AB  - The effect of long-term storage on alcohol stability in postmortem blood samples
      was investigated. Seventy-nine blood samples were used in this study. For the
      first time, blood alcohol concentrations were measured within 1 to 4 days after
      being taken at the Laboratory of Forensic Toxicology. After storage (ranging from
      191 to 468 days), each sample was reanalyzed for blood alcohol concentration, and
      results were compared with the original analysis. Results showed good agreement
      between the experimental measurements. About 90% of the results lie within 95%
      limits, and 10% were outside. Despite these positive correlations, the results of
      some blood samples showed a high variation in ethanol concentration. Deviation in
      alcohol concentration between replicates of up to 10% (observed in 39% samples)
      is not acceptable as precise forensic evidence.

PMID- 24457584
TI  - Morphine concentrations in skeletal muscle.
AB  - Skeletal muscle constitutes a large percentage of the total body volume, making
      it a potentially widely available specimen for drug quantitation when blood is
      not available for toxicological testing. Morphine is a commonly encountered
      opiate in postmortem toxicology known to have stable blood concentrations in
      peripheral vessels. Morphine concentrations were measured in both femoral blood
      and skeletal muscle to assess the stability and predictability of skeletal muscle
      concentrations as compared with femoral concentrations. Analysis showed skeletal
      muscle was a sensitive matrix for the detection of morphine; however, there is
      significant disparity between the skeletal muscle and blood concentrations with a
      lack of predictability. The authors conclude that thigh skeletal muscle may be
      used for qualitative identification of morphine; however, interpretation of
      quantitative results should not be made as there does not seem to be a clear
      correlation between femoral blood and skeletal muscle concentrations for
      morphine. 

PMID- 24457585
TI  - Effect of dactyloscopic powders on DNA profiling from enhanced fingerprints:
      results from an experimental study.
AB  - We conducted a study on the effect of fingerprint enhancement methods on
      subsequent short tandem repeat profiling. First, we performed a study typing
      blood traces deposited on 5 different surfaces, treated with 8 types of
      dactyloscopic powders. Three different DNA extraction methods were used.
      Subsequently, we analyzed latent fingerprints on the same 5 surfaces enhanced
      with the 8 different powders used in the first part of the study. This study has
      demonstrated that DNA profiling can be performed on fingerprints left on
      different substrates, and the substrate will affect the amount of DNA that can be
      recovered for DNA typing. In the first phase of the study, a profile was obtained
      in 92% of the 120 samples analyzed; in the second part, in 55% of the 80 samples
      analyzed, we obtained a profile complete in 32.5% of the cases. From the results
      obtained, it seems that the powders used in latent fingerprints enhancement,
      rather than having a direct inhibitory effect on extraction and amplification of
      DNA, may cause partial degradation of DNA, reducing the efficiency of
      amplification reaction. It should not be forgotten that these results were
      obtained under laboratory conditions, and in real caseworks, there may still be
      different problems involved.

PMID- 24457586
TI  - Pathological findings in 2 cases of fatal 25I-NBOMe toxicity.
AB  - The research compound 25I-NBOMe, also known as CIMBI-5 or INBMeO, was created in
      academic laboratories as a potent serotonin 2A receptor agonist. Because of its
      high affinity and ambiguous legal status, recreational drug enthusiasts have used
      this compound as a powerful alternative to other hallucinogenic drugs such as
      lysergic acid diethylamide. We report 2 deaths after 25I-NBOMe ingestion by
      decedents who attended separate "rave" parties. The first case involved a 21-year
      old male who admitted taking "acid" to his friend. A sudden violent rage caused
      him to flail about, and he subsequently became unresponsive. The postmortem
      examination revealed numerous external injuries that were consistent with
      physical aggression. The second case involved a 15-year-old female who was
      socializing outside a rave party, became ill, and rapidly deteriorated as her
      friend transported her to the hospital. The postmortem assessment was similar to
      the first case in that external contusions featured prominently. Comprehensive
      toxicology screens in both cases revealed only evidence of marijuana use. A
      deeper analysis using time-of-flight mass spectrometry revealed the presence of
      25I-NBOMe, which was further confirmed by tandem-mass spectrometry. The behavior
      and injuries in these cases reveal a consistent pattern preceding fatal 25I-NBOMe
      toxicity. 

PMID- 24457587
TI  - An experimental model of tool mark striations by a serrated blade in human soft
      tissues.
AB  - Tool mark analysis is a method of matching a weapon with the injury it caused. In
      a homicidal stabbing using a serrated knife, a stab wound that involves a
      cartilage may leave striations from the serration points on the blade edge.
      Assessing tissue striations is a means of identifying the weapon as having a
      serrated blade. This prospective study examines the possibility that similar
      striations may be produced in human soft tissues. Using tissues taken at the time
      of hospital-consented autopsies, stab wound tracks were assessed in a variety of
      human tissues (aorta, skin, liver, kidney, and cardiac and skeletal muscle). Stab
      wounds were produced postmortem with similar serrated and smooth-edged blades.
      The walls of the stab wounds were exposed, documented by photography and cast
      with dental impression material. Striations were identified by naked-eye
      examination in the skin and aorta. Photodocumentation of fresh tissue was best
      achieved in the aorta. Striations were not identified in wound tracks produced by
      the smooth-edged blade. Three blinded forensic pathologists were assessed for
      their ability to detect striations in photographs of wound tracks and had
      substantial interobserver agreement (kappa = 0.76) identifying striations. This
      study demonstrates that tool mark striations can be present in some
      noncartilaginous human tissues. 

PMID- 24457588
TI  - Instantaneous death due to transorbital reverse penetration of a screw in an
      accidental fall: unusual autopsy case report and review of the literature.
AB  - We present a peculiar autopsy case of a transorbital penetrating head injury, in
      a male worker, after an accidental fall onto a screw not completely stuck into a
      wooden board. A 13-cm screw entered the cranium 9.5 cm deep, penetrating with the
      flat end, a condition defined in literature as "reverse penetration." The death
      was instantaneous and caused by a neurogenic shock due to injuries to the brain
      stem and the right cerebellar hemisphere. These injuries, enabled by the length
      of the screw, are generally described in literature as due to nontransorbital
      penetrations, frequently associated with posterior entry and a large intracranial
      injury. The ocular globe has been, furthermore, perfectly preserved thanks to its
      mobility in the orbit. Even the dynamic of the incident is peculiar because of
      the stationary nature of the penetrating object, which the victim actively fell
      on by accident. To the best of our knowledge, the matter is therefore a very
      peculiar mortal case of transorbital intracranial penetration, whose verified
      injuries and dynamics are absolutely atypical. The case is now under discussion,
      and a review of pertinent literature is performed.

PMID- 24457589
TI  - Direct observation of liquid pre-crystallization intermediates during the
      reduction of aqueous tetrachloroaurate by sulfide ions.
AB  - Phenomena preceding precipitation of gold(i) sulfide in the reaction of aqueous
      tetrachloroauric acid with sodium sulfide have been studied applying several time
      resolved in situ techniques. As can be deduced from UV-vis absorption
      spectroscopy, soluble species ("pre-nucleation clusters") emerge within several
      seconds and slightly change with time; the spectra, along with the previous data
      for the immobilized products, are indicative of disordered matter with Au(I)-S
      bonding and the gap of about 1.5 eV. In situ tapping-mode atomic force microscopy
      (AFM) directly imaged "soft" droplet-like species from 20-50 nm to about 200 nm
      in the lateral size and the continuous film condensed on the highly oriented
      pyrolytic graphite (HOPG) support. Small-angle X-ray scattering (SAXS) revealed
      quasi-particles ("liquid clusters") growing to about 12 nm for 30 min, and slowly
      afterwards. Dynamic light scattering (DLS) was preferentially due to the larger
      species, although the liquid clusters within 20 nm comprise more than 80% of the
      total volume of the fluid products. The entities, which exist in solution for
      many hours before sudden gold sulfide sedimentation, are considered as "dense
      liquid" intermediates involved in a non-classical nucleation pathway.

PMID- 24457590
TI  - Prevention of post-stroke generalized anxiety disorder, using escitalopram or
      problem-solving therapy.
AB  - This study examined the efficacy of antidepressant treatment for preventing the
      onset of generalized anxiety disorder (GAD) among patients with recent stroke. Of
      799 patients assessed, 176 were randomized, and 149 patients without evidence of
      GAD at the initial visit were included in this double-blind treatment with
      escitalopram (N=47) or placebo (N=49) or non-blinded problem-solving therapy
      (PST; 12 total sessions; N=53). Participants given placebo over 12 months were
      4.95 times more likely to develop GAD than patients given escitalopram and 4.00
      times more likely to develop GAD than patients given PST. Although these results
      should be considered preliminary, the authors found that both escitalopram and
      PST were effective in preventing new onset of post-stroke GAD. 

PMID- 24457591
TI  - Lepidopteran sex determination: a cascade of surprises.
AB  - Sex determination is a developmental pathway that fixes the sexual fate (male or
      female) of an individual at early stages of embryonic development. This pathway
      is ideally suited for evolutionary studies given the astoundingly diverse
      mechanisms found in the animal kingdom. In particular, insects use multiple
      different cues to specify the sexual fate of an individual. In this review, we
      focus on genes and genetic interactions involved in the sex determination of
      insect species belonging to the order Lepidoptera. Unique features of the
      lepidopteran sex determination system are discussed.

PMID- 24457592
TI  - Reproducibility of a new colour test.
AB  - PURPOSE: To evaluate the reproducibility of a new colour test, using the
      Chromatometer CM3. METHODS: Twenty healthy subjects were recruited at the
      Department of Ophthalmology, at the Medical University of Vienna. A total of 40
      eyes were tested. Both eyes were tested separately with the Chromatometer CM3.
      The colour test was repeated after several days. Each time, best-corrected visual
      acuity was tested using Snellen charts, and colour perception was tested using
      the Chromatometer CM3. RESULTS: The Chromatometer CM3 showed reproducible results
      between the two tests at almost every luminosity level. All 4 green-red
      measurements and 2 blue-yellow brightness measurements showed reproducible
      results between the first and second tests. CONCLUSION: The Chromatometer CM3
      seems to be an appropriate method to detect changes in colour perception,
      although the red-green comparison appeared to be more precise than the blue
      yellow comparison.

PMID- 24457593
TI  - Synthesis, structure and reactivity of Fe(II/III)-NH3 complexes bearing a
      tripodal sulfonamido ligand.
AB  - Complexes [M(n)MST(NH3)](n-3) (M(n) = Fe(II), Fe(III), Ga(III)) were prepared and
      each contains an intramolecular hydrogen bonding network involving the ammonia
      ligand. Deprotonation of the Fe(III)-NH3 complex afforded a putative
      [Fe(III)MST(NH2)](-) species whose reactivity has been explored. 

PMID- 24457594
TI  - DNA damage in lens epithelial cells and peripheral lymphocytes from age-related
      cataract patients.
AB  - BACKGROUND: Oxidative DNA damage may be one of the etiologies of age-related
      cataract (ARC). We quantified DNA damage in lens epithelial cells (LECs) and
      peripheral blood lymphocytes of ARC. METHODS: A total of 64 patients with
      different types of ARC and 23 control subjects were enrolled. Fresh LECs and
      peripheral lymphocytes were collected and DNA damage was evaluated by alkaline
      comet assay. The percentage of DNA in the tail of comets (%Tail DNA) and the
      olive tail moment (OTM) were calculated by CASP software. RESULTS: The results
      showed the %Tail DNA and OTM in LECs and lymphocytes in the overall cataract
      patient group were significantly higher than those in the control subjects. The
      %Tail DNA and OTM of LECs and lymphocytes showed no differences among cortical,
      nuclear and posterior subcapsular cataracts. The %Tail DNA and OTM in LECs were
      significantly lower than those in lymphocytes but a significant correlation of
      the DNA damage was found between them. CONCLUSION: We concluded that DNA damage
      in lens and peripheral blood lymphocytes increased in ARC. The results imply that
      local and systemic oxidative DNA damage might play certain roles in ARC
      pathogenesis.

PMID- 24457595
TI  - Quantum dot-functionalized porous ZnO nanosheets as a visible light induced
      photoelectrochemical platform for DNA detection.
AB  - This work reports the synthesis of novel CdTe quantum dot (QD)-functionalized
      porous ZnO nanosheets via a covalent binding method with (3
      aminopropyl)triethoxysilane as a linker. The functional nanosheets showed an
      excellent visible-light absorbency and much higher photoelectrochemical activity
      than both CdTe QDs and ZnO nanosheets due to the porous structure and appropriate
      band alignment between the CdTe QDs and ZnO nanosheets. Using hydrogen peroxide
      as an electron acceptor the nanosheet-modified electrode showed a sensitive
      photocurrent response. This speciality led to a novel methodology for the design
      of hydrogen peroxide-related biosensors by the formation or consumption of
      hydrogen peroxide. Using biotin-labeled DNA as capture probe, a model biosensor
      was proposed by immobilizing the probe on a nanosheet-modified electrode to
      recognize target DNA in the presence of an assistant DNA, which produced a "Y"
      junction structure to trigger a restriction endonuclease-aided target recycling.
      The target recycling resulted in the release of biotin labeled to the immobilized
      DNA from the nanosheet-modified electrode, thus decreased the consumption of
      hydrogen peroxide by horseradish peroxidase-mediated electrochemical reduction
      after binding the left biotin with horseradish peroxidase-labeled streptavidin,
      which produced an increasing photoelectrochemical response. The 'signal on'
      strategy for photoelectrochemical detection of DNA showed a low detection limit
      down to the subfemtomole level and good specificity to single-base mismatched
      oligonucleotides. The sensitized porous ZnO nanosheets are promising for
      applications in both photovoltaic devices and photoelectrochemical biosensing. 

PMID- 24457596
TI  - Brain natriuretic peptide upon admission as a biological marker of short-term
      mortality after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to test the
      hypothesis that plasma brain natriuretic peptide (BNP) is associated with short
      term mortality after intracerebral hemorrhage (ICH). METHODS: We prospectively
      enrolled 271 patients (median age 72 years; 109 females) who were admitted within
      24 h of ICH onset between April 2007 and July 2011 and in whom plasma BNP levels
      were measured upon admission. The patients were assigned to two groups according
      to survival within 1 month of ICH. Factors associated with mortality were
      determined by multivariate logistic regression analysis. RESULTS: Within 1 month
      of ICH, 48 (17.7%) of the 271 enrolled patients died. The median (interquartile
      range) level of plasma BNP was significantly higher in the group of non-survivors
      than in the group of survivors [102.5 (48.7-205.0) vs. 32.4 (17.3-85.0) pg/ml; p
      < 0.001]. A cutoff BNP level of 60.0 pg/ml could predict death within 1 month of
      ICH. Multivariate logistic regression analysis showed that a plasma BNP of >60.0
      pg/ml (OR 4.7; 95% CI 1.43-15.63; p = 0.011) was independently associated with
      mortality within 1 month after ICH. CONCLUSIONS: A high BNP level upon admission
      is associated with mortality within 1 month after ICH.

PMID- 24457598
TI  - A dodecanuclear copper(II) cage self-assembled from six dicopper building units.
AB  - Reaction of the dinucleating phenol-based ligand, H3bpmp (2,6-bis-[(3-hydroxy
      propylimino)-methyl]-4-methyl-phenol), with Cu(2+) ions in the presence of a
      hybrid base (NEt3 and NaN3) necessary for the in situ generation of required
      numbers of hydroxido ions, results in the formation of a novel NO3(-) capped and
      HO(-) supported {Cu12} coordination complex {Cu6(MU3-OH)3(MU3-Hbpmp)3(MU3
      NO3)}2(NO3)2(OH)2.2H2O.2MeOH (1). When the components are combined in right
      proportions (metal : ligand : NEt3 : NaN3 = 2 : 1 : 3 : 2) in MeOH, twelve Cu(2+)
      ions assemble in a cuboctahedral geometry, containing six square and eight
      triangular faces around a considerable void space. Six of the eight [Cu3]
      triangular faces are bound by the six Hbpmp(2-) ligands with six free pendant
      propanol arms around the central hexagonal plane. X-ray structure determination
      indicates new geometrical features for the core formation and reveals the face
      capping potential of the H3bpmp ligand for the growth of a cuboctahedral
      coordination cage with the support of anions like HO(-) and NO3(-). The
      experimentally observed (J/kB = -173 K) strong antiferromagnetic coupling within
      the Cu12 complex has been justified by the DFT calculations.

PMID- 24457597
TI  - Metformin sensitizes anticancer effect of dasatinib in head and neck squamous
      cell carcinoma cells through AMPK-dependent ER stress.
AB  - Head and neck squamous cell carcinoma (HNSCC) is an important endemic disease in
      Taiwan with aggressive course and dismal outcome. Dasatinib is a Bcr-bl and Src
      kinase inhibitor that has potential against HNSCC. We recently disclosed that
      EGFR degradation is critical for dasatinib-induced apoptosis. Here, we further
      demonstrate that AMPK-dependent ER stress is responsible for this event.
      Dasatinib induced ER stress which mediated EGFR degradation in a c-cbl-dependent
      manner. AMPK activation induced by dasatinib might be due to ATP decrease through
      the up-regulation of pyruvate dehydrogenase kinase 4 (PDK4). Furthermore,
      activation of AMPK by metformin sensitized dasatinib-induced in vitro and in vivo
      anti-cancer effect. The correlation of AMPK activation and EGFR expression was
      seen in HNSCC cells and human tumor specimens. Our results disclose that AMPK
      dependent ER stress plays a crucial role in the anti-cancer effect of dasatinib
      in HNSCC and further activation of AMPK by metformin might enhance dasatinib
      efficacy. 

PMID- 24457599
TI  - Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment
      of hindlimb ischemia.
AB  - Currently, micro RNA (miRNA) is considered an attractive target for therapeutic
      intervention. A significant obstacle to the miRNA-based treatments is the
      efficient delivery of miRNA to the target tissue. We have developed polyethylene
      glycol-modified liposomes (Bubble liposomes (BLs)) that entrap ultrasound (US)
      contrast gas and can serve as both plasmid DNA (pDNA) or small interfering RNA
      (siRNA) carriers and US contrast agents. In this study, we investigated the
      usability of miRNA-loaded BLs (mi-BLs) using a hindlimb ischemia model and miR
      126. It has been reported that miR-126 promotes angiogenesis via the inhibition
      of negative regulators of VEGF signaling. We demonstrated that mi-BLs could be
      detected using diagnostic US and that mi-BLs with therapeutic US could deliver
      miR-126 to an ischemic hindlimb, leading to the induction of angiogenic factors
      and the improvement of blood flow. These results suggest that combining mi-BLs
      with US may be useful for US imaging and miRNA delivery. 

PMID- 24457601
TI  - Operation of a wet near-field scanning  optical microscope in stable zones by 
      minimizing the resonance change of  tuning forks.
AB  - A resonant shift and a decrease of resonance quality of a tuning fork attached to
      a conventional fiber optic probe in the vicinity of liquid is monitored
      systematically while varying the protrusion length and immersion depth of the
      probe. Stable zones where the resonance modification as a function of immersion
      depth is minimized are observed. A wet near-field scanning optical microscope
      (wet-NSOM) is operated for a sample within water by using such a stable zone.

PMID- 24457600
TI  - The central role of EED in the orchestration of polycomb group complexes.
AB  - Polycomb repressive complexes 1 and 2 (PRC1 and 2) play a critical role in the
      epigenetic regulation of transcription during cellular differentiation, stem cell
      pluripotency and neoplastic progression. Here we show that the polycomb group
      protein EED, a core component of PRC2, physically interacts with and functions as
      part of PRC1. Components of PRC1 and PRC2 compete for EED binding. EED functions
      to recruit PRC1 to H3K27me3 loci and enhances PRC1-mediated H2A ubiquitin E3
      ligase activity. Taken together, we suggest an integral role for EED as an
      epigenetic exchange factor coordinating the activities of PRC1 and 2. 

PMID- 24457602
TI  - Neuropsychiatric systemic lupus erythematosus: association with global disease
      activity.
AB  - OBJECTIVE: To determine whether patients with neuropsychiatric (NP) events
      attributed to systemic lupus erythematosus (SLE) have more global disease
      activity than patients with NP events not attributed to SLE. METHODS: Patients
      were recruited from an academic lupus clinic. Global disease activity was
      measured with the SLE Disease Activity Index 2000 (SLEDAI-2K) and organ damage
      with the Systemic Lupus International Collaborating Clinics (SLICC)/American
      College of Rheumatology (ACR) damage index (SDI). NP disease was defined using
      the ACR case definitions and decision rules for attribution of NP events to SLE
      and non-SLE causes. RESULTS: There were 68 patients (age (mean +/- SD) 40.8 +/-
      15.2 years, 85% female, 94% Caucasians) with 126 NP events. SLEDAI-2K scores in
      patients with NP events attributed to SLE were higher than in patients with NP
      events attributed to non-SLE causes even when NP variables were removed from the
      SLEDAI-2K (mean +/- SD: SLE NP = 7.36 +/- 5.42 vs non-SLE NP = 5.53 +/- 4.57, P =
      0.042). Patients with CNS and diffuse NP events, rather that PNS and focal
      events, accounted for the group differences in SLEDAI-2K scores. There were no
      significant differences in total SDI scores comparing NP events due to SLE vs.
      non-SLE causes (mean +/- SD: 2.1 +/- 1.8 vs. 1.7 +/- 1.7; p = 0.28) even when NP
      variables were omitted. CONCLUSIONS: Increased global SLE disease activity is
      associated with concurrent NP events attributed to SLE, particularly for diffuse
      NP and CNS NP events. The findings have diagnostic and therapeutic implications
      for SLE patients with NP events and inform pathogenetic mechanisms underlying
      NPSLE.

PMID- 24457604
TI  - Individualized vaginal bleeding experience of women with uterine fibroids in the
      PEARL I randomized controlled trial comparing the effects of ulipristal acetate
      or placebo.
AB  - RESEARCH QUESTION: What is the individualized bleeding experience of women with
      fibroids and anaemia in a 3 month randomized placebo controlled trial (PEARL I)
      of the selective progesterone receptor modulator (SPRM), ulipristal acetate
      (UPA)? SUMMARY ANSWER: In contrast to continuing excessive regular menstruation
      in the placebo group, a majority of women treated with UPA (63.1% of those on 5
      mg/day and 71.3% of those on 10 mg/day) experienced the rapid onset of
      amenorrhoea or minimal blood loss [pictorial blood loss assessment chart (PBAC) <
      12]. The remainder experienced various patterns of bleeding and intensity of
      blood loss that are described for the first time, including an association of
      irregular bleeding on UPA with sub-mucous fibroids. WHAT IS KNOWN ALREADY: The
      majority experience on UPA is amenorrhoea but the bleeding experience of the
      others has not been characterized. STUDY DESIGN, SIZE, DURATION: A 13 week
      randomized controlled trial in women, eligible for surgery for uterine fibroids
      and anaemia, comparing placebo (n = 48), UPA 5 mg (n = 95) or UPA 10 mg (n = 94).
      The treatment aim was fibroid shrinkage and the primary definitions and outcomes
      are published elsewhere; here the secondary outcome measure of vaginal bleeding
      pattern is described. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women, 18-50
      years old, with fibroids and haemoglobin <=10.2 g/dl, justifying surgery. At
      least one fibroid was 3-10 cm diameter and uterus <=16 weeks pregnancy size. All
      used the daily PBAC methodology in a screening cycle (Ps) and throughout
      treatment, and for the 4 weeks preceding Week 26 and Week 38 in those who did not
      have surgery. An excessive menstruation is PBAC > 100. The bleeding patterns were
      characterized using the classification of Belsey, developed under auspices of
      WHO. MAIN RESULTS AND THE ROLE OF CHANCE: In the placebo group, all women had an
      excessive screening PBAC [median 376; interquartile range (IQR) 241-574]; 81.3%
      of them had regular menstrual bleeding and the intensity of bleeding remained
      similar, so that the median PBAC in the next three periods was 90, 92 and 93% of
      the screening value. Four of the 48 women had spontaneous improvement in bleeding
      and one developed amenorrhoea and elevation of gonadotrophins. In the placebo
      group, 22 women provided Week 26 and 21 women provided Week 38 PBAC data. The
      median Week 26 PBAC (312: IQR 102-524) and Week 38 PBAC (236; IQR 103-465)
      indicated ongoing excessive bleeding. In the UPA group, screening PBAC confirmed
      excessive bleeding (UPA 5 mg, median 358; IQR 232-621; UPA 10 mg, median 330; IQR
      235-542). UPA was initiated from the start of a menstruation (P1) and no women
      had regular periods on treatment. Following P1 through the whole of the remaining
      13 weeks of UPA treatment amenorrhoea or minimal loss (PBAC < 12 for whole phase)
      occurred in 63.1% (UPA 5 mg) or 71.3% (UPA 10 mg). The characterization of the
      individualized bleeding experience of the remaining women on 5 mg and 10 mg UPA,
      respectively, were infrequent bleeding in 17.9 and 12.8%; frequent or prolonged
      bleeding or both in 12.7 and 11.7% and irregular bleeding in 5.3 and 3.2%. In
      those with prolonged, frequent or irregular bleeding there was a high chance that
      sub-mucous fibroids were present (UPA 5 mg 100% and UPA 10 mg 78.6%) but no
      correlation with progesterone receptor modulator-associated endometrial changes.
      LIMITATIONS, REASONS FOR CAUTION: The follow-up PBAC data at Week 26 and Week 38
      are only valid for women who did not have surgical intervention. These groups may
      not be representative of the groups at screening. WIDER IMPLICATIONS OF THE
      FINDINGS: This first detailed description of these SPRM bleeding patterns
      provides clinicians with an indication of potential responses in women using the
      SPRM UPA and provides an extended definition of bleeding in untreated women with
      excessive bleeding and fibroids. STUDY FUNDING/COMPETING INTEREST(S): Funded by
      PregLem/Gedeon Richter. D.H.B. is a member of the Scientific Advisory Board of
      PregLem, and in this role participated in the study design and supervision. Stock
      originally held in PregLem was given up when PregLem was incorporated into Gedeon
      Richter; D.H.B. does not currently hold stock. M.A.L. has received payment from
      Gideon Richter to attend a meeting to present these data (Barcelona, April 2013)
      but no financial support in preparing the manuscript. B.C.J.M.F. is a member of
      the Scientific Advisory Board of PregLem and has received fees and grant support
      from the following companies: Andromed, Ardana, Auxogyn, Ferring, Genovum, Gedeon
      Richter, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Roche,
      Schering, Schering Plough, Serono, Watson Laboratories and Wyeth. P.T. is a paid
      statistical consultant for PregLem SA. E.B. is a full time employee of PregLem
      and received payment from stocks sold in October 2010 from the company's full
      acquisition by Gedeon Richter Group. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov Identifier: NCT00755755 (PEARL I).

PMID- 24457603
TI  - Distinct DNA-based epigenetic switches trigger transcriptional activation of
      silent genes in human dermal fibroblasts.
AB  - The influential role of the epigenome in orchestrating genome-wide
      transcriptional activation instigates the demand for the artificial genetic
      switches with distinct DNA sequence recognition. Recently, we developed a novel
      class of epigenetically active small molecules called SAHA-PIPs by conjugating
      selective DNA binding pyrrole-imidazole polyamides (PIPs) with the histone
      deacetylase inhibitor SAHA. Screening studies revealed that certain SAHA-PIPs
      trigger targeted transcriptional activation of pluripotency and germ cell genes
      in mouse and human fibroblasts, respectively. Through microarray studies and
      functional analysis, here we demonstrate for the first time the remarkable
      ability of thirty-two different SAHA-PIPs to trigger the transcriptional
      activation of exclusive clusters of genes and noncoding RNAs. QRT-PCR validated
      the microarray data, and some SAHA-PIPs activated therapeutically significant
      genes like KSR2. Based on the aforementioned results, we propose the potential
      use of SAHA-PIPs as reagents capable of targeted transcriptional activation. 

PMID- 24457605
TI  - Isolation and preparation of bacterial cell walls for compositional analysis by
      ultra performance liquid chromatography.
AB  - The bacterial cell wall is critical for the determination of cell shape during
      growth and division, and maintains the mechanical integrity of cells in the face
      of turgor pressures several atmospheres in magnitude. Across the diverse shapes
      and sizes of the bacterial kingdom, the cell wall is composed of peptidoglycan, a
      macromolecular network of sugar strands crosslinked by short peptides.
      Peptidoglycan's central importance to bacterial physiology underlies its use as
      an antibiotic target and has motivated genetic, structural, and cell biological
      studies of how it is robustly assembled during growth and division. Nonetheless,
      extensive investigations are still required to fully characterize the key
      enzymatic activities in peptidoglycan synthesis and the chemical composition of
      bacterial cell walls. High Performance Liquid Chromatography (HPLC) is a powerful
      analytical method for quantifying differences in the chemical composition of the
      walls of bacteria grown under a variety of environmental and genetic conditions,
      but its throughput is often limited. Here, we present a straightforward procedure
      for the isolation and preparation of bacterial cell walls for biological analyses
      of peptidoglycan via HPLC and Ultra Performance Liquid Chromatography (UPLC), an
      extension of HPLC that utilizes pumps to deliver ultra-high pressures of up to
      15,000 psi, compared with 6,000 psi for HPLC. In combination with the preparation
      of bacterial cell walls presented here, the low-volume sample injectors,
      detectors with high sampling rates, smaller sample volumes, and shorter run times
      of UPLC will enable high resolution and throughput for novel discoveries of
      peptidoglycan composition and fundamental bacterial cell biology in most
      biological laboratories with access to an ultracentrifuge and UPLC. 

PMID- 24457606
TI  - Pharmacodynamic monitoring of nuclear factor of activated T cell-regulated gene
      expression in liver allograft recipients on immunosuppressive therapy with
      calcineurin inhibitors in the course of time and correlation with acute rejection
      episodes--a prospective study.
AB  - BACKGROUND: Due to considerable pharmacokinetic (PK) variability,
      immunosuppression with calcineurin inhibitors (CNIs) remains challenging. The
      objective of this study was to assess a pharmacodynamic (PD) approach of
      monitoring nuclear factor of activated T cell (NFAT)-regulated gene expression in
      the course of time and in correlation with rejection episodes. MATERIAL/METHODS:
      22 de novo liver allograft recipients were observed for a period of up to 12
      months and the residual gene expression (RGE) of NFAT-regulated genes was
      monitored prospectively and correlated to acute rejection episodes. RESULTS:
      There was a significant increase in RGEs between the time points 4-7 months and 1
      month (25+/-7 ug/l vs. 9+/-5 ug/l, p<=0.0001) and 8-12 months and 1 month (50+/-8
      ug/l vs. 10+/-7 ug/l, p=0.002) in the cyclosporine A (CsA) group, whereas in the
      tacrolimus (Tac) group a significant increase in RGEs appeared at the time point
      8-12 months first. Acute rejection episodes occurred in 4 patients within 1 month
      after transplantation. These patients demonstrated a higher RGE of all NFAT
      regulated genes compared to the other patients (CsA-treated patients: 39+/-0% vs.
      11+/-5%, p=0.0001, Tac-treated patients: 48+/-12% vs. 18+/-10%, p=0.0082).
      CONCLUSIONS: RGE of all NFAT-regulated genes show a relation between acute
      rejection episodes in the early post transplant period. Thus, this PD method has
      the potential to aid therapeutic drug monitoring.

PMID- 24457607
TI  - Change in composition of inflammatory infiltrate in the course of hepatitis C
      reinfection and concomitant acute rejection after orthotopic liver
      transplantation.
AB  - BACKGROUND: Hepatitis C virus (HCV) reinfection occurs in almost all patients
      after orthotopic liver transplantation (OLT) for HCV related liver cirrhosis and
      presents serious therapeutic challenge for a transplant team. The reinfection is
      concomitant with other posttransplant complications that influence presentation
      of the disease. Microscopic histological examination of a liver biopsy specimen
      remains the standard diagnostic procedure. The aim of the study was to analyze
      the composition of inflammatory infiltrate in HCV reinfection and determine
      whether its features may help in the differentiation between HCV reinfection and
      acute rejection (AR). MATERIAL/METHODS: Seventy seven post-OLT liver biopsy
      specimens from patients after OLT for HCV related cirrhosis were examined.
      Characteristics of inflammatory infiltrate and changes in its composition related
      to a time interval between OLT and biopsy and concomitant AR were analyzed.
      RESULTS: Significant differences in the composition of inflammatory infiltrate
      between the analyzed time intervals between OLT and biopsy were found. In the
      group of patients with HCV reinfection and concomitant AR the infiltrate was
      significantly more extensive than in the patients with HCV reinfection alone with
      predominantly CD8+ and CD5+ lymphocytes responsible for this finding.
      CONCLUSIONS: Significant changes in inflammatory infiltrate contents were found
      depending on the time period between OLT and graft biopsies.

PMID- 24457608
TI  - Removal of arterial lines and devices from the ascending aorta in cardiac surgery
      patients.
AB  - The use of monitoring or device lines through the ascending aorta may be
      necessary for a variety of clinical situations. The technique provided in this
      article allows percutaneous closure of these entry sites with a closed chest. 

PMID- 24457609
TI  - Gefitinib enhances the antitumor activity of CPT-11 in vitro and in vivo by
      inhibiting ABCG2 but not ABCB1: a new clue to circumvent gastrointestinal
      toxicity risk.
AB  - BACKGROUND: Despite the potent antitumor activity of CPT-11, late-onset diarrhea
      owing to enterohepatic circulation of SN-38 is a critical issue. METHODS: We
      aimed to evaluate the inhibitory potency of gefitinib against the ABCB1- or ABCG2
      mediated excretion of CPT-11 and its active metabolite SN-38 in vitro and in
      vivo. RESULTS: Gefitinib dose-dependently enhanced the antiproliferation activity
      of SN-38 in vitro by inhibiting ABCG2. The inhibitory effect of gefitinib on
      ABCB1 was marginal. When both CPT-11 and gefitinib were administered orally to
      nude mice bearing human lung cancer PC-6 cells, tumor growth was markedly
      suppressed. By gefitinib coadministration, the lactone forms of both CPT-11 and
      SN-38 in the tumor tissue increased more than 2-fold. CONCLUSIONS: Gefitinib
      significantly enhances the antitumor efficacy of CPT-11 and its tumor
      distribution in vivo. Coadministration of gefitinib may provide a new means to
      reduce the dose of CPT-11 and to circumvent the gastrointestinal toxicity risk.

PMID- 24457610
TI  - Finding the role of health care in population health.

PMID- 24457611
TI  - The use of zero-valent iron for groundwater remediation and wastewater treatment:
      a review.
AB  - Recent industrial and urban activities have led to elevated concentrations of a
      wide range of contaminants in groundwater and wastewater, which affect the health
      of millions of people worldwide. In recent years, the use of zero-valent iron
      (ZVI) for the treatment of toxic contaminants in groundwater and wastewater has
      received wide attention and encouraging treatment efficiencies have been
      documented. This paper gives an overview of the recent advances of ZVI and
      progress obtained during the groundwater remediation and wastewater treatment
      utilizing ZVI (including nanoscale zero-valent iron (nZVI)) for the removal of:
      (a) chlorinated organic compounds, (b) nitroaromatic compounds, (c) arsenic, (d)
      heavy metals, (e) nitrate, (f) dyes, and (g) phenol. Reaction mechanisms and
      removal efficiencies were studied and evaluated. It was found that ZVI materials
      with wide availability have appreciable removal efficiency for several types of
      contaminants. Concerning ZVI for future research, some suggestions are proposed
      and conclusions have been drawn. 

PMID- 24457612
TI  - Bioconcentration and distribution of silver nanoparticles in Japanese medaka
      (Oryzias latipes).
AB  - The study of the bioconcentration of silver nanoparticles (AgNPs) is important to
      fully understand their hazard potential in the aquatic environment. We
      synthesized AgNPs radiolabeled with silver isotopes ((110m)Ag) to quantify the
      bioconcentration of AgNPs coated with citrate (AgNPs-CIT) and
      polyvinylpyrrolidone (AgNPs-PVP) in Japanese medaka, and to investigate the
      biodistribution of silver in organs, which were compared with (110m)AgNO3. BCF
      values were determined to be 39.8+/-7.4, 42.5+/-5.1 and 116.4+/-6.1Lkg(-1) for
      AgNPs-CIT, AgNPs-PVP and AgNO3, respectively. The release of more silver ions in
      AgNPs-PVP contributed to a different kinetic uptake pattern with AgNPs-CIT, which
      was similar to that of AgNO3. Bioconcentrated AgNPs in medaka were not observed
      to be eliminated, independent of surface coating differences, similarly to AgNO3.
      There was no difference in biodistribution in each organ before and after
      depuration in two types of AgNPs and AgNO3, all of which were mainly concentrated
      in the liver. This study quantified the bioconcentration and distribution of
      AgNPs and AgNO3 more precisely by utilizing a silver isotope, which is helpful in
      monitoring the toxicity of AgNPs to Japanese medaka. 

PMID- 24457613
TI  - Online social networking sites-a novel setting for health promotion?
AB  - Among adolescents, online social networking sites (SNS) such as Facebook are
      popular platforms for social interaction and may therefore be considered as
      'novel settings' that could be exploited for health promotion. In this article,
      we examine the relevant definitions in health promotion and literature in order
      to analyze whether key characteristics of 'settings for health promotion' and the
      socio-ecological settings approach can be transferred to SNS. As many of our
      daily activities have shifted to cyberspace, we argue that online social
      interaction may gain more importance than geographic closeness for defining a
      'setting'. While exposition to positive references to risk behavior by peers may
      render the SNS environment detrimental to health, SNS may allow people to create
      their own content and therefore foster participation. However, those health
      promotion projects delivered on SNS up until today solely relied on health
      education directed at end users. It remains unclear how health promotion on SNS
      can meet other requirements of the settings approach (e.g. building partnerships,
      changing the environment). As yet, one should be cautious in terming SNS a
      'setting'. 

PMID- 24457615
TI  - Myostatin and sarcopenia: opportunities and challenges - a mini-review.
AB  - The progressive loss of skeletal muscle mass, strength and/or function with
      advancing age, termed sarcopenia, poses a major threat to independence and
      quality of life. Therefore, there is significant merit in better understanding
      the biology of sarcopenia and developing therapeutic interventions to prevent,
      slow or reverse its progression. Since the discovery of myostatin, a potent
      negative regulator of growth that is highly enriched in skeletal muscle, there
      has been great interest in it as a potential mediator of sarcopenia as well as a
      therapeutic target. The complex biology of myostatin, the promise of myostatin
      inhibition as an effective means to counter sarcopenia, and the challenges facing
      its clinical translation are reviewed herein.

PMID- 24457614
TI  - The prevalence, characteristics, and clinical significance of abnormal
      albuminuria in patients with hypertension.
AB  - Kidney function and cardiovascular disease are closely connected and albuminuria
      is a proven marker of cardiovascular risk. The present study investigated the
      prevalence and characteristics of albuminuria in patients with hypertension.
      Outpatients with essential hypertension under medical treatment were enrolled in
      this study (n = 350, 70.0 +/- 11.4 years old). Urine samples were collected for
      the measurement of albumin concentration, which are expressed as the ratio of
      urine albumin to creatinine concentration (mg/g Cr). Cross-sectional analyses
      were also performed of the relationships between urinary albumin and other
      variables. Urinary albumin was detected in 88.3% of patients, while only 35.4%
      showed abnormal albuminuria (>=30 mg/g Cr). The presence of abnormal albuminuria
      was independently correlated with systolic blood pressure, B-type natriuretic
      peptide, and C-reactive protein by multivariate analysis (P < 0.05). Furthermore,
      multivariate regression analysis identified systolic blood pressure, serum
      creatinine, B-type natriuretic peptide, and C-reactive protein as the only
      factors showing independent correlation with urinary albumin (P < 0.05). Thus,
      approximately 35% of hypertensive patients had abnormal albuminuria. Urinary
      albumin was closely associated with blood pressure, C-reactive protein, and B
      type natriuretic peptide, indicating that the severity of albuminuria parallels
      that of systemic inflammation, cardiac load, and blood pressure. 

PMID- 24457616
TI  - Open fetal surgery for central bronchial atresia.
AB  - Mainstem or lobar bronchial atresia is associated with massive pulmonary
      hyperplasia, contralateral pulmonary hypoplasia, non-immune hydrops and a fatal
      fetal prognosis. Open fetal surgery currently provides a potential therapeutic
      option for management of a fetus with this diagnosis. We present 2 cases of open
      fetal surgery for bronchial atresia at the level of the mainstem and lobar
      bronchus. The first case involved a left pneumonectomy performed at 26 weeks'
      gestation. After successful intraoperative resuscitation for fetal cardiac
      arrest, the fetus survived until 32 weeks' gestation when preterm premature
      rupture of membranes prompted delivery. The neonate expired on day of life
      (DOL)1. The second case involved a left upper lobectomy performed at 24(3)/7
      weeks' gestation. The fetus was delivered at 34(3)/7 weeks' gestation and, after
      a prolonged NICU course including a completion pneumonectomy and tracheostomy,
      was discharged home at 8 months of life. This second case is the first report of
      survival following open fetal surgery for central bronchial atresia. This report
      highlights the potential benefit of fetal lung resection for central bronchial
      atresia while describing the many challenges to achieve the successful management
      of a fetus with this condition.

PMID- 24457617
TI  - Layered zeolitic materials: an approach to designing versatile functional solids.
AB  - Relevant layered zeolites have been considered in this perspective article from
      the point of view of the synthesis methodologies, materials characterization and
      catalytic implications, considering the unique physico-chemical characteristics
      of lamellar materials. The potential of layered zeolitic precursors to generate
      novel lamellar accessible zeolites through swelling, intercalation,
      pillarization, delamination and/or exfoliation treatments is studied, showing the
      chemical, functional and structural versatility exhibited by layered zeolites.
      Recent approaches based on the assembly of zeolitic nanosheets which act as
      inorganic structural units through the use of dual structural directing agents,
      the selective modification of germanosilicates and the direct generation of
      lamellar hybrid organic-inorganic aluminosilicates are also considered to obtain
      layered solids with well-defined functionalities. The catalytic applications of
      the layered zeolites are also highlighted, pointing out the high accessibility
      and reactivity of active sites present in the lamellar framework. 

PMID- 24457618
TI  - High-density assembly of chemiluminescence functionalized gold nanodots on
      multiwalled carbon nanotubes and their application as biosensing platforms.
AB  - A one-step strategy was developed for high-density assembly of N-(aminobutyl)-N
      (ethylisoluminol) (ABEI) functionalized gold nanodots onto the sidewalls of
      chitosan-grafted multiwalled carbon nanotubes (cs-MWCNTs) via the reduction of
      HAuCl4 with ABEI in the presence of cs-MWCNTs, resulting in novel hybrid
      nanomaterials with excellent chemiluminescence and electrochemiluminescence
      properties. 

PMID- 24457619
TI  - Aqueous asymmetric cyclopropanation reactions in polymersome membranes.
AB  - Copper-bis(oxazoline) complexes have been immobilised in the hydrophobic domain
      of a polymersome membrane to perform asymmetric cyclopropanation reactions in
      aqueous media with enhanced conversions and enantioselectivities. 

PMID- 24457620
TI  - 5-Fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX)
      as second-line chemotherapy in patients with advanced pancreatic cancer who have
      progressed on gemcitabine-based therapy.
AB  - BACKGROUND/AIMS: There is no standard consensus on a strategy in the second-line
      setting for gemcitabine-refractory advanced pancreatic cancer. This study
      evaluated the activity and tolerability of oxaliplatin, irinotecan, 5
      fluorouracil and leucovorin (FOLFIRINOX) as a second-line therapy in advanced
      pancreatic adenocarcinoma pretreated with a gemcitabine-based regimen. METHODS: A
      retrospective survey was carried out on 18 patients with advanced pancreatic
      cancer who had been on gemcitabine-based chemotherapy and were then treated with
      FOLFIRINOX as a second-line therapy. RESULTS: One patient (5.6%) had a confirmed
      complete response, 4 (22.2%) had confirmed partial responses and 5 (27.8%) had
      stable disease, resulting in a rate of disease control of 55.6% (95% CI, 33.3
      77.8%). The median progression-free survival and median survival were 2.8 months
      and 8.4 months, respectively. Seven patients (38.9%) experienced grade 3-4
      neutropenia. Grade 3 or 4 nonhematologic adverse events included nausea (38.9%)
      and vomiting (16.7%). CONCLUSIONS: These results suggest the modest clinical
      activity regarding efficacy and the acceptable toxicity profile with the
      FOLFIRINOX regimen as a second-line treatment.

PMID- 24457621
TI  - Kinetics study of heterogeneous reactions of ozone with erucic acid using an ATR
      IR flow reactor.
AB  - The ozone initiated heterogeneous oxidation of erucic acid (EA) thin film was
      investigated using a flow system combined with attenuated total reflection
      infrared spectroscopy (ATR-IR) over wide ranges of ozone concentrations (0.25-60
      ppm), thin film thickness (0.1-1.0 MUm), temperatures (263-298 K), and relative
      humidities (0-80% RH) for the first time. Pseudo-first-order rate constants,
      kapp, and overall reactive uptake coefficients, gamma, were obtained through
      changes in the absorbance of C[double bond, length as m-dash]O stretching bands
      at 1695 cm(-1), which is assigned to the carbonyl group in carboxylic acid.
      Results showed that the reaction followed the Langmuir-Hinshelwood mechanism and
      kapp was largely dominated by surface reaction over bulk phase reaction. In
      addition, both the kapp and the gamma values showed very strong temperature
      dependences (~two orders of magnitude) over the temperature range; in contrast,
      they only slightly increased with increasing RH values from 0-80%. According to
      the kapp values as a function of temperature, the activation energy for the
      heterogeneous reaction was estimated to be 80.6 kJ mol(-1). Our results have
      suggested that heterogeneous reactions between ozone and unsaturated solid
      surfaces likely have a substantially greater temperature dependence than liquid
      ones. Moreover, the hygroscopic properties of EA thin films before and after
      exposure to ozone were also studied by measurement of water uptake. Based on the
      hygroscopicity data, the insignificant RH effect on reaction kinetics was
      probably due to the relatively weak water uptake by the unreacted and reacted EA
      thin films. 

PMID- 24457622
TI  - Neutrophil elastase as a diagnostic marker and therapeutic target in colorectal
      cancers.
AB  - Neutrophil elastase (NE), a serine protease secreted by neutrophils, contributes
      to the progression of cancers to enhance tumor invasion and metastasis. It has
      been well reported that the regions surrounding the colorectal cancerous tissues
      usually are decorated with increased accumulation or aggregation of neutrophils
      coupled with a higher deposition/expression of NE. Therefore, we hypothesized
      that an increased expressional level of NE in patients with colorectal cancer
      (CRC) may represent as one of putative biomarkers for CRC. The aim of this study
      was to evaluate and assure our hypothesis by measurements of the expressional
      level of NE in the sera and tissues from CRC patients. Moreover, we also proposed
      a potential therapeutic strategy by blocking enzymatic activity of NE using
      sivelestat to inhibit the progression of tumor developments. The infiltrated
      numbers of neutrophils from specimen tissues of CRC patients, and the secreted
      forms of NE in the sera were quantitatively measured and compared. To evaluate
      the serum NE as one of putative biomarkers of CRC patients, the receiver
      operating characteristic (ROC) curve was made to determine the cut-off value of
      NE in sera for assurance of CRC diagnosis. To evaluate NE as therapeutic target
      for CRC, sivelestat, a NE inhibitor, was used and administrated into the CRC
      xenografts. NE expression level coupled with tumor volume were measured and
      compared between the control and sivelestat-treated xenografts. We found that
      more infiltrated neutrophils and an increased NE expression were detected in the
      cancerous tissues compared to the normal tissues. The serum NE concentration in
      CRC patients was statistically higher than that in the healthy controls (0.56 +/-
      0.08 MUg/ml vs. 0.22 +/- 0.03 MUg/ml) (p<0.05), indicating that serum NE can
      potentially be a putative marker of CRC. To characterize the role of NE in
      tumorigenesis, the NE activity was detected in HCT-15-xenografts using in vivo
      imaging system (IVIS). Compare to normal mice, the amounts of active NE in
      xenografts are significantly higher than normal control animals. In the
      therapeutic characterizing studies, we found that sivelestat can inhibit tumor
      growth in the HCT-15-induced xenografts. This study suggests that NE is not only
      as a putative diagnostic biomarker of CRC, but also a potential therapeutic
      target for patients suffered with CRC.

PMID- 24457624
TI  - Evaluation of cognitive characteristics of patients developing manifestations of
      parkinsonism secondary to long-term ephedrone use.
AB  - AIM: In this study, cognitive functions of 9 patients developing parkinsonism due
      to chronic manganese intoxication by intravenous methcathinone solution were
      investigated using detailed neuropsychometric tests. METHOD: Attention deficit,
      verbal and nonverbal memory, visuospatial function, constructive ability,
      language, and executive (frontal) functions of 9 patients who were admitted to
      our clinic with manifestations of chronic manganese intoxication and 9 control
      subjects were assessed using neuropsychometric tests. Two years later, detailed
      repeat neuropsychometric tests were performed in the patient group. The results
      were evaluated using the chi(2) test, Fisher's exact probability test, Student's
      t test and the Mann-Whitney U test. RESULTS: While there was no statistically
      significant difference between the two groups in language functions, visuospatial
      functions and constructive ability, a statistically significant difference was
      noted between both groups regarding attention (p = 0.032), calculation (p =
      0.004), recall and recognition domains of verbal memory, nonverbal memory (p =
      0.021) and some domains of frontal functions (Stroop-5 and spontaneous recovery)
      (p = 0.022 and 0.012). Repeat neuropsychometric test results of the patients were
      not statistically significant 2 years later. CONCLUSION: It has been observed
      that cognitive dysfunction seen in parkinsonism secondary to chronic manganese
      intoxication may be long-lasting and may not recover as observed in motor
      dysfunction.

PMID- 24457623
TI  - Therapeutic potential of somatic cell nuclear transfer for degenerative disease
      caused by mitochondrial DNA mutations.
AB  - Induced pluripotent stem cells (iPSCs) hold much promise in the quest for
      personalised cell therapies. However, the persistence of founder cell
      mitochondrial DNA (mtDNA) mutations limits the potential of iPSCs in the
      development of treatments for mtDNA disease. This problem may be overcome by
      using oocytes containing healthy mtDNA, to induce somatic cell nuclear
      reprogramming. However, the extent to which somatic cell mtDNA persists following
      fusion with human oocytes is unknown. Here we show that human nuclear transfer
      (NT) embryos contain very low levels of somatic cell mtDNA. In light of a recent
      report that embryonic stem cells can be derived from human NT embryos, our
      results highlight the therapeutic potential of NT for mtDNA disease, and
      underscore the importance of using human oocytes to pursue this goal. 

PMID- 24457626
TI  - Reducing the impact of intrinsic dissipation in a superconducting circuit by
      quantum error detection.
AB  - A fundamental challenge for quantum information processing is reducing the impact
      of environmentally induced errors. Here we demonstrate a quantum error detection
      and rejection protocol based on the idea of quantum uncollapsing, using this
      protocol to reduce the impact of energy relaxation owing to the environment in a
      three-qubit superconducting circuit. We encode quantum information in a target
      qubit, and use the other two qubits to detect and reject errors caused by energy
      relaxation. This protocol improves the storage time of a quantum state by a
      factor of roughly three, at the cost of a reduced probability of success. This
      constitutes the first experimental demonstration of the algorithm-based
      improvement in the lifetime of a quantum state stored in a qubit. 

PMID- 24457625
TI  - Impact of oxidative/nitrosative stress and inflammation on cognitive functions in
      patients with recurrent depressive disorders.
AB  - Data show that up to 38.2% of the European population have a mental disorder and
      that recurrent depressive disorder (rDD) is among the most commonly diagnosed
      disabling diseases. Over the last few years, neurocognitive impairments in rDD
      have become a new research front focusing on the role of cognitive decline during
      the course of rDD and in relation to its clinical presentation and prognosis.
      Both immune-inflammatory and oxidative and nitrosative stress (O&NS) processes
      potentially play a role in development of cognitive dysfunction in rDD. New
      evidence shows that chronic inflammatory and O&NS reactions occur in the brains
      of patients with neurodegenerative disorders and those with rDD. This narrative
      review presents the current state of knowledge on the possible impact of selected
      inflammatory and O&NS enzymes on cognitive functioning in patients with rDD. We
      focus on manganese superoxide dismutase (MnSOD), inducible nitric oxide synthase
      (iNOS), and myeloperoxidase (MPO). 

PMID- 24457627
TI  - Thyroidectomy for Graves' disease: a feasibility study of the robotic
      transaxillary approach.
AB  - INTRODUCTION: Graves' disease (GD) is considered a relative contraindication for
      endoscopic approaches to the thyroid gland, due to a larger gland size and
      increased vascularity. METHODS: A retrospective analysis of a single surgeon's
      experience was performed. We included all patients who underwent thyroidectomy
      for the treatment of GD over a 3-year period. RESULTS: Twenty-five patients with
      GD were identified. Twelve of them underwent robotic thyroidectomy and 13
      patients underwent conventional thyroidectomy. Age, gender, and BMI were similar
      in both groups (p > 0.05). The conventional approach allowed for resection of
      larger thyroid volumes (147.3 +/- 153.6 ml), as compared to the robotic approach
      (62.3 +/- 47.8 ml, p = 0.08). The average total operative times were similar in
      both groups (p = 0.98). There was no difference with respect to intraoperative
      blood loss (p = 0.49), duration of hospital stay (p = 0.38), and complication
      rates (p = 0.99). CONCLUSION: Robotic thyroidectomy is feasible and can be safely
      performed in appropriately selected patients with GD.

PMID- 24457628
TI  - Spontaneous core-shell elemental  distribution in In-rich In(x)Ga1-xN nanowires 
      grown by molecular beam epitaxy.
AB  - The elemental distribution of self-organized In-rich In(x)Ga1-xN nanowires grown
      by plasma-assisted molecular beam epitaxy has been investigated using three
      different techniques with spatial resolution on the nanoscale. Two-dimensional
      images and elemental profiles of single nanowires obtained by x-ray fluorescence
      and energy-dispersive x-ray spectroscopy, respectively, have revealed a radial
      gradient in the alloy composition of each individual nanowire. The spectral
      selectivity of resonant Raman scattering has been used to enhance the signal from
      very small volumes with different elemental composition within single nanowires.
      The combination of the three techniques has provided sufficient sensitivity and
      spatial resolution to prove the spontaneous formation of a core-shell nanowire
      and to quantify the thicknesses and alloy compositions of the core and shell
      regions. A theoretical model based on continuum elastic theory has been used to
      estimate the strain fields present in such inhomogeneous nanowires. These results
      suggest new strategies for achieving high quality nonpolar heterostructures.

PMID- 24457629
TI  - Determining the ice-binding planes of antifreeze proteins by fluorescence-based
      ice plane affinity.
AB  - Antifreeze proteins (AFPs) are expressed in a variety of cold-hardy organisms to
      prevent or slow internal ice growth. AFPs bind to specific planes of ice through
      their ice-binding surfaces. Fluorescence-based ice plane affinity (FIPA) analysis
      is a modified technique used to determine the ice planes to which the AFPs bind.
      FIPA is based on the original ice-etching method for determining AFP-bound ice
      planes. It produces clearer images in a shortened experimental time. In FIPA
      analysis, AFPs are fluorescently labeled with a chimeric tag or a covalent dye
      then slowly incorporated into a macroscopic single ice crystal, which has been
      preformed into a hemisphere and oriented to determine the a- and c-axes. The AFP
      bound ice hemisphere is imaged under UV light to visualize AFP-bound planes using
      filters to block out nonspecific light. Fluorescent labeling of the AFPs allows
      real-time monitoring of AFP adsorption into ice. The labels have been found not
      to influence the planes to which AFPs bind. FIPA analysis also introduces the
      option to bind more than one differently tagged AFP on the same single ice
      crystal to help differentiate their binding planes. These applications of FIPA
      are helping to advance our understanding of how AFPs bind to ice to halt its
      growth and why many AFP-producing organisms express multiple AFP isoforms. 

PMID- 24457630
TI  - Endoscopic endonasal transpterygoid transmaxillary approach to the infratemporal
      and upper parapharyngeal tumors.
AB  - OBJECTIVES: To describe the endoscopic transnasal approach to the infratemporal
      fossa (ITF) and upper parapharyngeal space (UPS) and to analyze the indications
      and outcomes of this surgical technique in the management of the tumors localized
      in this critical area. STUDY DESIGN: Case series with chart review. SETTING:
      Tertiary-care referral center. PATIENTS AND METHODS: Retrospective review of
      patients with benign and malignant tumors arising in or extending to the ITF and
      UPS, treated from 2002 to 2012 at a single institute. The tumors were surgically
      resected using an endoscopic endonasal transpterygoid transmaxillary approach.
      RESULTS: Thirty-seven consecutive patients with benign tumors (20 juvenile
      nasopharyngeal angiofibromas, 2 extracranial trigeminal Schwannomas, 2
      meningiomas, 1 cavernous hemangioma) and nonmetastatic malignant tumors (2
      adenoid-cystic carcinoma, 1 mucoepidermoid carcinoma, 1 squamous cell carcinoma,
      1 adenocarcinoma, 1 recurrence of chondrosarcoma, and 6 recurrences of
      undifferentiated carcinoma of nasopharyngeal type) were treated with curative
      intent. A gross-total resection was achieved in 35 of 37 patients. Major
      complications were observed in 1 case (intraoperative internal carotid artery
      blowout). Postoperatively, 8 patients received some form of adjuvant treatment.
      Mean follow-up was 30 months for malignancies and 60 months for benign tumors.
      All patients are now alive without recurrences. Stable intracranial persistence
      of disease was reported in 2 cases (1 meningioma and 1 adenoid-cystic carcinoma).
      CONCLUSION: The purely endoscopic endonasal technique may provide a minimally
      invasive and safe approach to radically resect selected tumors involving the ITF
      and UPS. Larger case series and longer follow-up are needed to validate the
      reproducibility and efficacy of this technique.

PMID- 24457631
TI  - Latent Tuberculosis screening using interferon-gamma release assays in an
      Australian HIV-infected cohort: is routine testing worthwhile?
AB  - BACKGROUND: There are limited data from high-income countries on the performance
      of interferon-gamma release assays in screening for latent tuberculosis infection
      (LTBI). We analyzed the routine application of the Quantiferon-TB Gold (QFT-G)
      assay to detect and predict latent and active TB among HIV-infected patients in
      Australia. METHODS: A retrospective cohort study included all HIV-infected
      patients attending the Melbourne Sexual Health Service between March 2003 and
      February 2011 who were screened for LTBI using QFT-G. Clinical data were analyzed
      in multivariable models to determine predictors for QFT-G positivity using
      logistic regression and active TB development using Cox proportional hazards.
      RESULTS: Nine hundred seventeen HIV-infected patients had >=1 QFT-G performed, of
      whom 884 (96.4%) were negative, 29 (3.2%) positive, and 4 (0.4%) indeterminate.
      The mean age was 40.9 years and 88% were male, with median follow-up of 26.4
      (interquartile range 15.4-30.7) months. Five hundred fifty (63%) were Australian
      born, whereas 198 (23%) were born in Asia or Africa. QFT-G was positive in 2.0%
      of Australian-born, 5.3% of overseas-born [odds ratio: 2.6, 95% confidence
      interval (CI): 1.2 to 5.6, P = 0.017], and 12.7% of African-born patients (odds
      ratio 7.1, 95% CI: 2.9 to 17.3, P < 0.001). Two cases of culture-positive TB
      occurred after QFT-G screening in 3.4% of QFT-G-positive and 0.1% of QFT-G
      negative patients (adjusted hazard ratio: 42.4, 95% CI: 2.2 to 827, P = 0.013), a
      rate of 111 (95% CI: 27.8 to 445) per 100,000 person-years. CONCLUSIONS: In this
      context, QFT-G has a high negative predictive (99.9%) value with few
      indeterminate results. A risk stratification approach to LTBI screening, where
      HIV-infected patients with epidemiological risk factors for TB infection undergo
      QFT-G testing, might be clinically appropriate and potentially cost effective in
      similar settings.

PMID- 24457632
TI  - A randomized open-label study of 3- versus 5-drug combination antiretroviral
      therapy in newly HIV-1-infected individuals.
AB  - BACKGROUND: To understand whether combination antiretroviral therapy (cART) has
      been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART
      intensified with raltegravir and maraviroc and initiated during early infection
      would improve outcomes when compared with similarly applied 3-drug PI-based cART.
      METHODS: Forty newly HIV-1-infected patients were randomized 1:2 to receive 3
      drug (N = 14) or 5-drug (N = 26) therapy. The primary end point was the percent
      of subjects with undetectable plasma viremia using standard reverse transcriptase
      polymerase chain reaction and the single copy assay after 48 weeks. Secondary end
      points included levels of cell-associated HIV-1 DNA and RNA and levels of
      infectious virus in resting CD4 T cells at week 96 and quantitative and
      qualitative immunologic responses. RESULTS: At 48 weeks, 34 subjects remained on
      study and are included in the as-treated analysis. Three of 11 (27.3%) in the 3
      drug arm and 9 of 21 (42.9%) in the 5-drug arm had plasma HIV-1 RNA levels below
      detection by both standard reverse transcriptase-polymerase chain reaction and
      single copy assay (P = 0.46, Fisher exact test). No significant differences in
      absolute levels of proviral DNA or changes in cell-associated RNA were seen
      during 96 weeks of therapy. Mean levels of infectious HIV-1 in resting CD4 T
      cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67
      and 0.71 infectious units per million, respectively (P = 0.81). No differences
      were seen in quantitative or qualitative immunologic determinations including
      markers of immune activation. CONCLUSIONS: Intensified 5-drug cART initiated
      during early infection fails to significantly further impact virologic or
      immunologic responses beyond those achieved with standard 3-drug PI-based cART.

PMID- 24457634
TI  - HIV infection and its association with an excess risk of clinical fractures: a
      nationwide case-control study.
AB  - BACKGROUND: Different studies have reported an association between HIV infection,
      antiretroviral therapies, and impaired bone metabolism, but data on their impact
      on fracture risk are scarce. We studied the association between a clinical
      diagnosis of HIV infection and fracture risk. METHODS: We conducted a case
      control study using data from the Danish National Health Service registries,
      including 124,655 fracture cases and 373,962 age- and gender-matched controls.
      Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using
      conditional logistic regression. RESULTS: A total of 50 (0.40/1000) patients in
      the fracture group and 52 (0.14/1000) controls had an HIV diagnosis. The risk of
      any fracture was thus significantly increased among HIV-infected patients (age-
      and gender-matched OR = 2.89, 95% CI: 1.99 to 4.18). Similarly, significant
      increases in the risk of hip (OR = 8.99, 95% CI: 1.39 to 58.0), forearm (OR =
      3.50, 95% CI: 1.26 to 9.72), and spine fractures (OR = 9.00, 95% CI: 1.39 to
      58.1) were observed. CONCLUSIONS: HIV infection is associated with an almost 3
      fold increase in fracture risk compared with that of age- and gender-matched
      uninfected patients. HIV patients are also at an almost 9-fold higher risk of hip
      fracture.

PMID- 24457635
TI  - Cadaveric feasibility study of da Vinci Si-assisted cochlear implant with
      augmented visual navigation for otologic surgery.
AB  - IMPORTANCE: To our knowledge, this is the first reported cadaveric feasibility
      study of a master-slave-assisted cochlear implant procedure in the otolaryngology
      head and neck surgery field using the da Vinci Si system (da Vinci Surgical
      System; Intuitive Surgical, Inc). We describe the surgical workflow adaptations
      using a minimally invasive system and image guidance integrating intraoperative
      cone beam computed tomography through augmented reality. OBJECTIVE: To test the
      feasibility of da Vinci Si-assisted cochlear implant surgery with augmented
      reality, with visualization of critical structures and facilitation with precise
      cochleostomy for electrode insertion. DESIGN AND SETTING: Cadaveric case study of
      bilateral cochlear implant approaches conducted at Intuitive Surgical Inc,
      Sunnyvale, California. INTERVENTIONS: Bilateral cadaveric mastoidectomies,
      posterior tympanostomies, and cochleostomies were performed using the da Vinci Si
      system on a single adult human donor cadaveric specimen. MAIN OUTCOMES AND
      MEASURES: Radiographic confirmation of successful cochleostomies, placement of a
      phantom cochlear implant wire, and visual confirmation of critical anatomic
      structures (facial nerve, cochlea, and round window) in augmented
      stereoendoscopy. RESULTS: With a surgical mean time of 160 minutes per side,
      complete bilateral cochlear implant procedures were successfully performed with
      no violation of critical structures, notably the facial nerve, chorda tympani,
      sigmoid sinus, dura, or ossicles. Augmented reality image overlay of the facial
      nerve, round window position, and basal turn of the cochlea was precise.
      Postoperative cone beam computed tomography scans confirmed successful placement
      of the phantom implant electrode array into the basal turn of the cochlea.
      CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first study in the
      otolaryngology-head and neck surgery literature examining the use of master-slave
      assisted cochleostomy with augmented reality for cochlear implants using the da
      Vinci Si system. The described system for cochleostomy has the potential to
      improve the surgeon's confidence, as well as surgical safety, efficiency, and
      precision by filtering tremor. The integration of augmented reality may be
      valuable for surgeons dealing with complex cases of congenital anatomic
      abnormality, for revision cochlear implant with distorted anatomy and poorly
      pneumatized mastoids, and as a method of interactive teaching. Further research
      into the cost-benefit ratio of da Vinci Si-assisted otologic surgery, as well as
      refinements of the proposed workflow, are required before considering clinical
      studies.

PMID- 24457633
TI  - Antiviral activity of genital tract secretions after oral or topical tenofovir
      pre-exposure prophylaxis for HIV-1.
AB  - BACKGROUND: Surrogate markers of HIV-1 pre-exposure prophylaxis and microbicide
      efficacy are needed. One potential surrogate is the antiviral activity in
      cervicovaginal lavage (CVL) after exposure to candidate products. We measured CVL
      antiviral activity in women using oral or vaginal tenofovir-based pre-exposure
      prophylaxis and correlated activity with drug and immune mediator levels.
      METHODS: Inhibitory activity against HIV-1 and herpes simplex virus (HSV)-2 and
      concentrations of interleukin (IL)-1beta, IL-6, IL-8, interferon-gamma, induced
      protein 10 (IP-10), macrophage inflammatory protein (MIP)-1alpha, MIP-3a,
      lactoferrin, secretory leukocyte protease inhibitor, and defensins were measured
      in CVL obtained from 60 women at baseline and after 6 weeks of a randomized
      sequence of oral and topical tenofovir. CVL tenofovir concentrations were
      measured by mass spectrometry. RESULTS: The number of women with CVL anti-HIV
      activity >= 90% increased significantly from 5.0% at baseline to 89.1% after
      daily use of 1% tenofovir gel (relative risk = 17.85, P < 0.001), but there was
      no increase after daily oral tenofovir. The CVL anti-HIV activity correlated with
      drug levels (Spearman correlation coefficient 0.64 after tenofovir gel; P <
      0.001) but not with the concentrations of mucosal immune mediators. No increase
      in CVL anti-HSV activity was observed after either drug regimen, an observation
      consistent with the higher concentrations of tenofovir needed to inhibit HSV-2
      infection. The CVL anti-HSV activity correlated with lactoferrin, defensins, IP
      10, IL-8, and detectable levels of MIP-1alpha but not with drug levels.
      CONCLUSIONS: CVL may provide a surrogate for local but not systemic drug efficacy
      and a tool to better understand mucosal factors that modulate antiviral activity
      in genital tract secretions.

PMID- 24457636
TI  - Study of behavior: science or pseudoscience (with comments of Bogdan Dreher,
      Giacomo Rizzolatti and Charles Gross).
AB  - The manuscript printed below has been written by Professor Jerzy Konorski around
      1970, a few years before his death in 1973. The manuscript has not been published
      before. It was recently discovered in Konorski's papers deposed in the Library of
      the Nencki Institute of Experimental Biology. In his critical review Konorski
      debates advantages and shortcomings of the physiological approach of Pavlov and
      purely behavioristic approaches advocated by Hull and Skinner. He supports close
      cooperation o behaviorists with neurophysiologists and neuroanatomists, with
      focus on the investigation of the neural mechanisms underlying behavior.
      Konorski's ideas concerning the integration of the study of behavior and
      neurophysiology anticipated contemporary path of neuroscience. Indeed, his
      approach, which at that time appeared somewhat controversial, is universally
      accepted by contemporary neuroscientists. By contrast, physiological theories of
      higher mental functions formulated by Pavlov as well as deliberately anti
      physiological approaches of Skinner and Hull have all but disappeared from
      serious scientific discourse. However, the same problems such as strongly
      promoted self-importance of some branches of neuroscience, the lack of inter
      communication between different branches and resulting lack of integrating ideas
      appear to emerge anew in each new generation of scientists. (Editors of Acta
      Neurobiologiae Experimentalis). 

PMID- 24457637
TI  - Looking back at Jerzy Konorski's book "Integrative Activity of the Brain" 45
      years after.
AB  - This article presents historical background preceding writing and publication of
      Jerzy Konorski book "Integrative Activity of the Brain" followed by a short
      description of the main topics covered in the book. Two new and original
      contributions of Konorski are presented in detail, his theory of the motivational
      processes and the organization of the sensory systems in the brain. Those two
      contributions are then incorporated in the revised theory of the classical and
      type II conditioned reflexes which constitutes the core of the book. Conclusions
      point out at some of the ideas which remained valuable for the present day
      neuroscientists. 

PMID- 24457638
TI  - Gnostic cells in the 21st century.
AB  - In this short review, I revise the notion of gnostic cells posited by Konorski,
      together with similar arguments by James, Lettvin and Barlow--namely, the idea of
      pontifical, grandmother and cardinal cells, respectively. I then discuss whether
      the characteristics of the recently discovered concept cells, i.e. neurons in the
      human medial temporal lobe with a very high degree of specificity and invariance,
      fit the conjecture of gnostic or grandmother cells and then discuss the key role
      of concept cells in memory formation.

PMID- 24457639
TI  - Animal models of schizophrenia: developmental preparation in rats.
AB  - Schizophrenia manifests itself primarily with positive symptoms, negative
      symptoms and cognitive disorders. Animal models of mental diseases seem to be an
      important tool in understanding key theories related with pathophysiology of the
      disorder and are used to assess efficacy of new drugs. References describe four
      basic groups of animal models of schizophrenia, such as: models created by
      pharmacological intervention, genetic models, lesion models and models of
      developmental disorders of primary brain structures. Of the models referred to
      above, the group of developmental disorder models is particularly noteworthy, as
      they are primarily easy to use, and the methods are highly sensitive. High
      scientific value of these models is associated with the neurodevelopmental theory
      which stipulates that at an early stage of body development, a number of
      interactions between genetic and environmental factors may affect the development
      of neurons which may cause disorders of brain cytoarchitecture development. We
      review six developmental models of schizophrenia in rats (MAM--methylooxymethanol
      acetate, prenatal stress, maternal deprivation, isolation rearing, prenatal
      immune challenge and maternal malnutrition) that are all validated by disruption
      in PPI.

PMID- 24457640
TI  - Leukemia inhibitory factor inhibits the proliferation of primary rat astrocytes
      induced by oxygen-glucose deprivation.
AB  - Leukemia inhibitory factor (LIF) is a neuroprotective cytokine that is necessary
      for the normal development of astrocytes. Oxygen-glucose deprivation (OGD) can
      induce astrocyte proliferation by increasing hypoxia-inducible factor alpha (HIF
      1alpha) and vascular endothelial growth factor (VEGF). Here, we studied whether
      LIF affects the proliferation of cultured primary rat astrocytes under OGD
      conditions by measuring EdU incorporation into astrocyte DNA and the expression
      of proliferating cell nuclear antigen (PCNA) mRNA and protein. Our findings show
      that low concentrations of LIF (5 and 10 ng/mL) significantly decreased EdU
      incorporation and downregulated the expression of PCNA mRNA and PCNA protein in
      astrocytes subjected to OGD. A low concentration of LIF (10 ng/mL) clearly
      inhibited astrocyte proliferation induced by OGD, while a higher concentration
      (50 ng/mL) had no effect. To investigate the mechanism of this inhibition by LIF
      (10 ng/mL), the expression of 3 related genes (LIF receptor, HIF-1alpha, and
      VEGF) was assessed using real-time PCR; VEGF protein expression was measured by
      Western blot. Our results indicate that LIFR mRNA was downregulated in astrocytes
      subjected to OGD. Interestingly, treatment with LIF further reduced LIFR mRNA
      expression in these cells. LIF treatment also decreased the expression of HIF
      1alpha mRNA, VEGF mRNA, and VEGF protein induced by OGD. Low concentrations of
      LIF were observed to inhibit astrocyte proliferation induced by OGD. 

PMID- 24457641
TI  - The effects of serotonin, dopamine, octopamine and tyramine on behavior of
      workers of the ant Formica polyctena during dyadic aggression tests.
AB  - We investigated the effect of injections of four biogenic amines (serotonin,
      dopamine, octopamine and tyramine) on behavior patterns displayed by workers of
      the red wood ant Formica polyctena during dyadic confrontations with four types
      of opponents: a nestmate, an alien conspecific, an allospecific ant (Formica
      fusca), and a potential prey, a nymph of the house cricket (Acheta domesticus).
      Significant effects of biogenic amine administration were observed almost
      exclusively in the case of confrontations with allospecific opponents. Serotonin
      treatment exerted stimulatory effects on behavior patterns involving physical
      aggression (biting accompanied by gaster flexing, dragging and formic acid
      spraying), but these effects were relatively weak and/or documented by indirect
      evidence. Dopamine administration exerted a stimulatory effect on open-mandible
      threats directed by F. polyctena to F. fusca and to cricket nymphs, and on biting
      behavior directed to cricket nymphs. Surprisingly, octopamine treatment did not
      exert significant effects on aggressive behavior of the tested ants. Tyramine
      administration exerted a suppressing effect on threatening behavior directed to
      F. fusca, but led to shortening of the latencies to the first open-mandible
      threat during the tests with cricket nymphs. Biogenic amine administration also
      influenced non-aggressive behavior of the tested ants. Our findings confirmed the
      role of serotonin and dopamine in the mediation of ant aggressive behavior and
      documented for the first time significant effects of tyramine treatment on ant
      aggressive behavior. We also demonstrated that not only specific patterns of ant
      aggressive behavior, but also behavioral effects of biogenic amine treatments are
      as a rule strongly context-dependent. 

PMID- 24457642
TI  - The effect of pressure on potassium currents in the inner hair cells isolated
      from guinea-pig cochlea.
AB  - An increase in hydrostatic pressure in the endolymphatic system causes hydrops
      related inner ear diseases such as Meniere's disease or low tone sensorineural
      hearing loss. In the present study, we investigated the effects of pressure
      exerted on potassium currents in acutely isolated inner hair cells of the guinea
      pig cochlea using whole-cell voltage-clamp techniques. By applying negative or
      positive pressure via the patch pipette using a syringe, intracellular
      hydropressure was changed between -40 cm H2O to +20 cm H2O. Negative pressure
      potentiated the amplitude of potassium currents, whereas positive pressure
      suppressed the amplitude of potassium currents. Gadolinium, a blocker of stretch
      activated cation channels, did not influence pressure-dependent changes in
      potassium currents; however, cinnarizine blocked pressure-dependent changes in
      potassium currents. The current changes were not dependent on the sign of the
      pressure change, that is, similar increases in negative pressures (between -10 cm
      H2O and -40 cm H2O) and similar decreases in positive pressures (between +10 cm
      H2O and +20 cm H2O) were observed. 

PMID- 24457643
TI  - Correlation between dopaminergic phenotype and expression of calretinin in the
      midbrain nuclei of the opossum (Monodelphis domestica): an immunohistological
      study.
AB  - We investigated distribution and morphology of neurons of the midbrain nuclei:
      the ventral tegmental area (VTA), substantia nigra (SN) and periaqueductal gray
      (PAG) of the adult grey short-tailed opossums that were double immunolabeled for
      the presence of calretinin (CR) and/or tyrosine hydroxylase (TH). The majority of
      TH-immunopositive neurons and fibers were located in the VTA, SN, and only scarce
      population of small neurons expressing TH was present in the PAG. In the SN 80
      percent of TH-expressing neurons had large cell bodies, and only a small fraction
      had small perikarya. In the PAG populations of large and medium sized neurons
      were equal and 20 percent of neurons had small perikarya. Much scarcer population
      of TH-immunoreactive neurons in the PAG consisted of large or small neurons in
      its dorsal part (PAGd) and almost exclusively small neurons in the ventral part
      (PAGv). Distribution of neurons expressing TH and their types in the opossum are
      similar to those in rodents. The majority of CR-immunolabeled neurons were found
      in the VTA. In its subdivision, the parabrachal pigmented nucleus (PBP) cells
      expressing CR were approximately 28 percent more numerous than cells expressing
      TH. In spite of that, only 42 percent of TH-expressing neurons coexpressed CR.
      The high degree of colocalization TH and CR was observed in the SN. We propose
      that a higher percentage of TH/CR colocalization, which is observed in the
      opossums SN, may give them the ability to adapt to changes in their motor
      functions. 

PMID- 24457644
TI  - Dynein c1h1, dynactin and syntaphilin expression in brain areas related to
      neurodegenerative diseases following exposure to rotenone.
AB  - Neurodegeneration is often accompanied by protein inclusions which may interfere
      with cell physiology. On the other hand, alteration in intracellular trafficking
      may precede impairment of neurotransmission and therefore trigger cell death. In
      view of this, it is hypothesized that changes in mitochondrial traffic may occur
      before neurodegeneration triggered by rotenone exposure and could favor this
      process. The effects of low concentrations of rotenone on the expression of
      dynein c1h1, dynactin and syntaphilin, which are proteins related to mitochondria
      transport and anchoring, were evaluated in cell cultures of substantia nigra,
      locus coeruleus and hippocampus as well as in these same brain areas in Lewis
      aged rats. The results indicate that low concentrations of rotenone decrease
      dynein c1h1 protein levels in cell cultures and brain areas of aged rats.
      Dynactin is decreased after exposure to 0.1 and 0.3 nM of rotenone, and increased
      after exposure to 0.5 nM of rotenone in cell cultures. Aged rats present
      increased dynactin expression. Syntaphilin expression decreased in vitro and
      increased in vivo after rotenone exposure. These findings suggest that changes in
      protein expression related to mitochondrial retrograde transport and anchoring
      occur before neurodegeneration induced by rotenone exposure, which may be a
      primary factor to trigger neurodegenerative mechanisms. 

PMID- 24457645
TI  - Ultrasonic vocalizations (USV) in the three standard laboratory mouse strains:
      developmental analysis.
AB  - Mice, similarly to some other rodent species, communicate with specialized sounds
      in the ultrasonic range called ultrasonic vocalizations (USV). Evaluation of this
      behavioral activity enables estimation of the social interactions in animal
      models of autistic spectrum disorders (ASD). Because transgenic mouse models are
      generated, in most cases, on the mixed 129SV/C57BL6 genetic background, we were
      interested if parameters that characterize USV differ between these two mouse
      strains. In addition, we wanted to compare these strains with the BALB/c line. In
      order to analyze USV, we applied the standard isolation test to newborn animals
      and compared standard parameters. Obtained results indicate clear differences
      between the 129SV and C57BL6 strains in respect to all analyzed USV parameters.
      Both strains behave also differently when compared with the BALB/c strain. For
      this reason in experiments utilizing transgenic animals, contribution of various
      genetic backgrounds has to be carefully considered. 

PMID- 24457646
TI  - Does brain ability to synchronize with 40 Hz auditory stimulation change with
      age?
AB  - Auditory steady-state responses (ASSRs) are widely applied to test brain ability
      to follow external stimulation and this appeared to be a promising method in
      neuropsychiatric disorders. Nevertheless, there is no established conclusion on
      the way aging affects phase-locking measures of ASSRs in healthy subjects. We
      aimed to identify the effects of aging on phaselocking measures of 40 Hz ASSR.
      The effect of aging was tested in a sample of 46 healthy male subjects (20-58
      years old) during eyes open condition. Stimuli were 500 ms trains, consisting of
      20 identical clicks (1.5 ms burst of white noise) delivered binaurally. Time
      frequency analysis of the data was performed and phase-locking index, evoked
      amplitude and total intensity measures were extracted and decomposed by non
      negative multi-way factorization. As shown by curve-fitting analyses, phase
      locking index and evoked amplitudes were diminishing with age in the linear
      manner. This was also proven by ANOVA testing when sample was divided into age
      groups. No effect of age on the total intensity was found. The complexity of the
      factors modulating the 40 Hz ASSR is not entirely solved; nevertheless, the
      current results suggest that the ability to synchronize to high frequency
      external stimulation diminishes with age. This should be taken into account,
      particularly when ASSRs are used in clinical practice, comparing patients and
      healthy subjects. 

PMID- 24457647
TI  - Expression of the type 1 metalloproteinase in the rat hippocampus after the
      intracerebroventricular injection of beta-amyloid peptide (25-35).
AB  - The expression of matrix metalloproteinase of the first type was studied in
      frontal sections of the adult rat brain one month after a single
      intracerebroventricular injection of beta-amyloid peptide (25-35), which is known
      to be a well-known model of the development of Alzheimer's disease. Brain
      sections were stained immunocytochemically to detect MMP-1 expression, and
      histologically to reveal the state of hippocampal neurons. Administration of beta
      amyloid peptide induced a significant degeneration of cells in the dorsal
      hippocampus. This was demonstrated by a significant decrease in the total number
      of cells and by the appearance of acidophilic neurons of altered (often
      triangular) shape. Altered cells were most often found in the hippocampal field
      CA3, and in a smaller quantity in the CA1 field. MMP-1-like immunoreactivity was
      found in the same hippocampal areas, the staining being restricted to the cells
      of altered shape (staining of somata and primary neurites). The data suggest
      possible involvement of the type 1 metalloproteinase in the development of
      Alzheimer's disease. 

PMID- 24457648
TI  - Vascular risk factors, cardiovascular disease and functional impairment in
      community-dwelling adults.
AB  - BACKGROUND: Older adults report preservation of functional independence as one of
      the most important constructs of successful ageing. Vascular risk factors may
      increase the risk of functional impairment due to clinical and subclinical
      vascular disease. OBJECTIVE: To describe the association between vascular risk
      factors and impaired ability to perform daily living activities, independent of
      established cardiovascular disease. METHODS: We conducted an analysis of the
      Clarity Cohort, which is a cross-sectional study of 9,816 community-dwelling
      Irish adults. Of the total cohort, 3,499 completed standardized self-reported
      health questionnaires, which included questions on activities of daily living.
      Functional impairment was defined as self-reported impairment in self-care,
      mobility or household tasks. Using logistic regression analyses, we determined
      the association between vascular risk factors and functional impairment,
      independent of demographics, prior coronary artery disease, stroke, congestive
      heart failure, and peripheral vascular disease. RESULTS: Functional impairment
      was reported in 40.4% (n = 1,413) of the cohort overall and in 23% of those with
      established cardiovascular disease. The mean age was 66.2 +/- 10.3 years, 52% of
      the cohort were aged over 65 and 45.6% were male. Some difficulty with
      instrumental activities of daily living was reported by 35.4% (n = 1,240) while
      29.4% (n = 1,029) reported some difficulty with basic activities of daily living.
      On multivariable analysis, older age [OR 1.03 (1.02, 1.04) per year], current
      smoking [OR 1.43 (1.08, 1.89)], atrial fibrillation [OR 1.68 (1.07, 2.65)],
      former alcohol use [OR 1.87 (1.36, 2.57)] and prior stroke [OR 1.91 (1.24, 2.93)]
      were associated with an increased risk of functional impairment. Older age
      leaving education [OR 0.96 (0.94, 0.99)], non-use of alcohol [OR 0.76 (0.61,
      0.93)] and increased high-density lipoprotein levels [OR 0.70 (0.56, 0.88)] were
      associated with reduced risk of functional impairment. CONCLUSIONS: Independent
      of established cardiovascular disease, some vascular risk factors are associated
      with functional impairment. Modification of these risk factors is expected to
      have a large impact on preservation of functional independence through prevention
      of overt and covert vascular disease.

PMID- 24457811
TI  - Update on the diagnosis and classification of fetal growth restriction and
      proposal of a stage-based management protocol.
AB  - Small fetuses are defined as those with an ultrasound estimated weight below a
      threshold, most commonly the 10th centile. The first clinically relevant step is
      the distinction of 'true' fetal growth restriction (FGR), associated with signs
      of abnormal fetoplacental function and poorer perinatal outcome, from
      constitutional small-for-gestational age, with a near-normal perinatal outcome.
      Nowadays such a distinction should not be based solely on umbilical artery
      Doppler, since this index detects only early-onset severe forms. FGR should be
      diagnosed in the presence of any of the factors associated with a poorer
      perinatal outcome, including Doppler cerebroplacental ratio, uterine artery
      Doppler, a growth centile below the 3rd centile, and, possibly in the near
      future, maternal angiogenic factors. Once the diagnosis is established,
      differentiating into early- and late-onset FGR is useful mainly for research
      purposes, because it distinguishes two clear phenotypes with differences in
      severity, association with preeclampsia, and the natural history of fetal
      deterioration. As a second clinically relevant step, management of FGR and the
      decision to deliver aims at an optimal balance between minimizing fetal injury or
      death versus the risks of iatrogenic preterm delivery. We propose a protocol that
      integrates current evidence to classify stages of fetal deterioration and
      establishes follow-up intervals and optimal delivery timings, which may
      facilitate decisions and reduce practice variability in this complex clinical
      condition.

PMID- 24457812
TI  - Detection of sugar alcohol-specific IgE.

PMID- 24457813
TI  - Usefulness of a new therapy using rebamipide eyedrops in patients with VKC/AKC
      refractory to conventional anti-allergic treatments.
AB  - BACKGROUND: Rebamipide, a gastroprotective drug, has been reported to suppress
      gastric mucosal inflammation. In Japan, rebamipide eyedrops have recently been
      approved for the treatment of dry eye disease. Some patients with allergic
      conjunctival diseases such as vernal keratoconjunctivitis (VKC) or atopic
      keratoconjunctivitis (AKC) manifest dry eye with decreased tear break-up time
      only. We report patients with VKC/AKC refractory to anti-allergic treatments who
      responded to the combination of rebamipide eyedrops and conventional anti
      allergic treatments with anti-allergic- and/or immunosuppressive/steroid
      eyedrops. METHODS: Four patients with allergic conjunctival diseases with giant
      papillae (VKC or AKC) instilled rebamipide eyedrops three or four times a day for
      varying periods. All had dry eye with decreased tear break-up time. We evaluated
      changes in the size of their giant papillae using Image J software. RESULTS: We
      observed attenuation of the giant papillae in all 4 patients. In 2 patients with
      severe disease, whose giant papillae had become larger despite the administration
      of tacrolimus and steroids, the addition of rebamipide contributed to their
      attenuation. In 2 patients with mild disease, the giant papillae had become
      larger or remained the same size despite the administration of anti-allergy
      drugs; the addition of rebamipide eyedrops also resulted in the attenuation of
      their giant papillae. CONCLUSIONS: Our findings suggest that rebamipide eyedrops
      might attenuate giant papillae in patients with allergic conjunctival diseases
      and that these eyedrops may be useful for the treatment of not only dry eye but
      also of allergic conjunctival diseases.

PMID- 24457814
TI  - Analysis of the influenza A (H1N1) 2009 pandemic infection in Japanese asthmatic
      patients: using a questionnaire-based survey.
AB  - BACKGROUND: Influenza infection is known to be an exacerbating factor in the
      control of asthma, therfore its prevention is critical in managing asthma. The
      aim of this study was to investigate the influenza A H1N1 2009 pandemic virus
      (H1N1 pdm09) infection in adult asthmatic patients. METHODS: Data were obtained
      from a questionnaire-based survey of asthmatic patients conducted from September
      to October 2010 in Niigata Prefecture. Patient background, H1N1 pdm09 infection,
      vaccination status, and asthma exacerbation due to influenza infection were
      analyzed. RESULTS: In total, 2,555 cases were analyzed. The incidence of the
      infection was 6.7% (95% confidence interval [CI]: 5.7-7.6), and the rate of
      vaccination was 63.9% (95% CI: 62.1-65.8). The odds ratio (OR) for vaccination
      against the infection among adult patients and younger patients (<= the median
      age) were 0.61 (95% CI: 0.45-0.84) and 0.62 (95% CI: 0.42-0.90), respectively.
      However, OR among the older patient (> median age) were 1.38 (95%CI: 0.66-2.89).
      The rate of infection-induced asthma exacerbation was 23.2% (95% CI: 18.6-29.6),
      and the OR for vaccination against the infection-induced asthma exacerbation was
      1.42 (95% CI: 0.69-2.92). CONCLUSIONS: The effectiveness of the vaccination
      against the H1N1 pdm09 virus was confirmed during the first pandemic season, but
      it was limited. Further investigation on H1N1 pdm09 virus infection in asthmatics
      will be required.

PMID- 24457815
TI  - Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and
      cholinergic urticaria.
AB  - BACKGROUND: MGL_1304 secreted by Malassezia globosa is contained in human sweat
      and induces histamine release from basophils in patients with atopic dermatitis
      (AD) at a high positive rate. The aims of this study were to establish the enzyme
      linked immunosorbent assay (ELISA) measuring specific immunoglobulins against
      MGL_1304 and to investigate the levels of these immunoglobulins in sera of
      patients with various allergic diseases. METHODS: Purified MGL_1304 from human
      sweat (QRX) and recombinant MGL_1304 (rMGL_1304) were prepared for ELISA. To
      quantify the amount of MGL_1304-specific immunoglobulins, the standard serum was
      created by pooling sera of 20 patients with AD whose basophils released histamine
      in response to QRX. A monoclonal antibody which exhibited the highest
      neutralizing ability against QRX was established as Smith-2, and used as a
      capture antibody for the assay of QRX-specific IgE. A total of 156 subjects
      [normal controls (n = 23), AD (n = 63), cholinergic urticaria (CU) (n = 24),
      bronchial asthma (n = 32), and allergic rhinitis (n = 14)] were enrolled in this
      study. RESULTS: ELISA methods to quantify the specific IgE, IgG and IgG4 against
      MGL_1304 in sera were successfully established. Levels of QRX-specific IgE in
      sera of patients with AD and CU were significantly higher than those of normal
      controls. Moreover, the levels of QRX-specific IgE and rMGL_1304-specific IgE in
      patients with AD were significantly correlated with their disease severities.
      CONCLUSIONS: These ELISA methods to quantify the specific immunoglobulins against
      MGL_1304 are easy and useful means to assess allergy to MGL_1304. MGL_1304
      contained in sweat is an important antigen for patients with AD and CU.

PMID- 24457816
TI  - Disease prevention in the age of convergence - the need for a wider, long ranging
      and collaborative vision.
AB  - It is time to bring our imagination, creativity and passion to the fore in
      solving the global challenges of our age. Our global health crisis and the
      pandemic of noncommunicable diseases (NCDs) is clearly rooted in complex modern
      societal and environmental changes, many of which have effects on developing
      immune and metabolic responses. It is intimately related to wider environmental
      challenges. And it is unsurprising that many NCDs share similar risk factors and
      that many are associated with a rising predisposition for inflammation. Allergy
      is one of the earliest signs of environmental impact on these biological
      pathways, and may also offer an early barometer to assess the effects of early
      interventions. There is dawning awareness of how changing microbial diversity,
      nutritional patterns, sedentary indoor behaviours and modern pollutants adversely
      affect early metabolic and immune development, but still much to understand the
      complexity of these interactions. Even when we do harness the science and
      technology, these will not provide solutions unless we also address the wider
      social, cultural and economic determinants of health - addressing the
      interconnections between human health and the health of our environment. Now more
      than ever, we need a wider vision and a greater sense of collective
      responsibility. We need long-range approaches that aim for life long benefits of
      a 'healthier start to life', and stronger cross-sectoral collaborations to
      prevent disease. We need to give both our hearts and our minds to solving these
      global issues. 

PMID- 24457817
TI  - Modified Robicsek procedure for pectus excavatum in adult patients.
AB  - OBJECTIVES: The aim of this study was to clarify the short-term and mid-term
      outcomes of the modified Robicsek procedure using polypropylene mesh for adult
      pectus excavatum patients. METHODS: Retrospective chart review was performed.
      Between 2001 and 2012, 46 consecutive adult patients underwent modified Ravitch
      repair using polypropylene mesh for pectus excavatum at our institution. There
      were 30 males and 16 females, with a median age of 25.5 (range: from 17 to 60).
      Potential risk factors for perioperative complications and early failure in
      pectus repair were analysed with chi(2) test or Fisher's exact test and Mann
      Whitney test. Potential risk factors for postoperative mid-term recurrence were
      analysed using Cox proportional hazard regression model. RESULTS: The
      postoperative follow-up interval was 7.0 +/- 15.1 months (mean +/- standard
      deviation). No mortality and 11 patients (24.0%) of morbidity, including 2
      patients with temporary mesh infection, were noted. A lower preoperative %FEV1.0
      predicted was a significant factor (P = 0.0088) of morbidity in multivariate
      analysis. Regarding chest morphology, early failure in 1 patient (2.2%) and mid
      term recurrence in 1 patient (2.2%) were seen. Previous pectus repair (P =
      0.0324) and severe asymmetry (P = 0.04) were significant factors of early failure
      in multivariate analysis, while no significant factor for mid-term recurrence was
      found. CONCLUSIONS: Modified Robicsek procedure with a polypropylene mesh is
      associated with low incidences of early failure and mid-term recurrence. The
      procedure is recommended for adult pectus excavatum patients, including those
      with asymmetric or combined deformity as an initial or reoperative procedure.

PMID- 24457818
TI  - Disseminated coccidioidomycosis in a 5-year-old Sudanese boy.
AB  - A 5-year-old Sudanese boy not known to be immunodeficient and with no history of
      travelling developed septic shock from a disseminating coccidial infection. The
      diagnosis was delayed, as the eosinophilic hepatic abscess was initially thought
      to be secondary to schistosomiasis, which is endemic in Egypt and Sudan. A
      further survey about the existence of coccidial infection around the climatic
      area of the river Nile is warranted.

PMID- 24457819
TI  - A prognostic model based on preoperative MRI predicts overall survival in
      patients with diffuse gliomas.
AB  - BACKGROUND AND PURPOSE: Diffuse gliomas are classified as grades II-IV on the
      basis of histologic features, with prognosis determined mainly by clinical
      factors and histologic grade supported by molecular markers. Our aim was to
      evaluate, in patients with diffuse gliomas, the relationship of relative CBV and
      ADC values to overall survival. In addition, we also propose a prognostic model
      based on preoperative MR imaging findings that predicts survival independent of
      histopathology. MATERIALS AND METHODS: We conducted a retrospective analysis of
      the preoperative diffusion and perfusion MR imaging in 126 histologically
      confirmed diffuse gliomas. Median relative CBV and ADC values were selected for
      quantitative analysis. Survival univariate analysis was made by constructing
      survival curves by using the Kaplan-Meier method and comparing subgroups by log
      rank probability tests. A Cox regression model was made for multivariate
      analysis. RESULTS: The study included 126 diffuse gliomas (median follow-up of
      14.5 months). ADC and relative CBV values had a significant influence on overall
      survival. Median overall survival for patients with ADC < 0.799 * 10(-3) mm(2)/s
      was <1 year. Multivariate analysis revealed that patient age, relative CBV, and
      ADC values were associated with survival independent of pathology. The
      preoperative model provides greater ability to predict survival than that
      obtained by histologic grade alone. CONCLUSIONS: ADC values had a better
      correlation with overall survival than relative CBV values. A preoperative
      prognostic model based on patient age, relative CBV, and ADC values predicted
      overall survival of patients with diffuse gliomas independent of pathology. This
      preoperative model provides a more accurate predictor of survival than histologic
      grade alone.

PMID- 24457820
TI  - MR imaging evolution of endoscopic cranial defect reconstructions using
      nasoseptal flaps and their distinction from neoplasm.
AB  - BACKGROUND AND PURPOSE: Endoscopic endonasal approach is the procedure of choice
      for the resection of ventral skull base neoplasms, with defect closure requiring
      multilayer reconstruction. This study evaluates the temporal MR imaging evolution
      of nasoseptal flaps and free grafts used in endoscopic skull base reconstruction.
      MATERIALS AND METHODS: Sixty-nine follow-up brain MRIs of 22 patients who had
      endoscopic skull base reconstruction using 26 nasoseptal flaps combined with 8
      collagen-matrix dural grafts, 10 fascia lata grafts, and 10 intracranial fat
      grafts were retrospectively reviewed. Temporal changes in signal intensity,
      enhancement, thickness, and the configuration of reconstructive layers were
      evaluated. Tissue with signal intensity or enhancement different from that of
      normal evolving reconstructive layers at the surgical bed was evaluated, and its
      association with clinically confirmed tumor was assessed with the Fisher exact
      test. RESULTS: All normal reconstructive layers were retracted to cranial defects
      and showed maturation of imaging features within 2-6 months. The immediate
      postoperative T2-isointensity to brain and enhancement of nasoseptal flaps
      persisted, but the flap thickness was reduced by 20%-30% (average thickness, 4.5
      +/- 1.3 mm); additionally, the C shape and vascular pedicle of the nasoseptal
      flaps became indistinct, but the flap location remained unchanged. The initial
      appearance of the nonenhancing fascia lata with variable T2 signal intensity
      became enhancing with increasing T2-hypointensity and a graft-thickness reduction
      of >=50% (average thickness, 3.5 +/- 1.6 mm). All fat grafts showed progressive
      resorption. In 6 patients, abnormal tissue represented residual or recurrent
      tumor (P = .0001). CONCLUSIONS: Maturation and stability of multilayer endoscopic
      skull base reconstructions on MR imaging occurs within 2-6 months
      postoperatively. Understanding of the normal imaging evolution of endoscopic
      skull base reconstructions is essential to distinguish them from neoplasms.

PMID- 24457821
TI  - Artifact reduction of different metallic implants in flat detector C-arm CT.
AB  - BACKGROUND AND PURPOSE: Flat detector CT has been increasingly used as a follow
      up examination after endovascular intervention. Metal artifact reduction has been
      successfully demonstrated in coil mass cases, but only in a small series. We
      attempted to objectively and subjectively evaluate the feasibility of metal
      artifact reduction with various metallic objects and coil lengths. MATERIALS AND
      METHODS: We retrospectively reprocessed the flat detector CT data of 28 patients
      (15 men, 13 women; mean age, 55.6 years) after they underwent endovascular
      treatment (20 coiling +/- stent placement, 6 liquid embolizers) or shunt drainage
      (n = 2) between January 2009 and November 2011 by using a metal artifact
      reduction correction algorithm. We measured CT value ranges and noise by using
      region-of-interest methods, and 2 experienced neuroradiologists rated the degrees
      of improved imaging quality and artifact reduction by comparing uncorrected and
      corrected images. RESULTS: After we applied the metal artifact reduction
      algorithm, the CT value ranges and the noise were substantially reduced (1815.3
      +/- 793.7 versus 231.7 +/- 95.9 and 319.9 +/- 136.6 versus 45.9 +/- 14.0; both P
      < .001) regardless of the types of metallic objects and various sizes of coil
      masses. The rater study achieved an overall improvement of imaging quality and
      artifact reduction (85.7% and 78.6% of cases by 2 raters, respectively), with the
      greatest improvement in the coiling group, moderate improvement in the liquid
      embolizers, and the smallest improvement in ventricular shunting (overall
      agreement, 0.857). CONCLUSIONS: The metal artifact reduction algorithm
      substantially reduced artifacts and improved the objective image quality in every
      studied case. It also allowed improved diagnostic confidence in most cases.

PMID- 24457822
TI  - Genetics of amyotrophic lateral sclerosis.

PMID- 24457824
TI  - Balloon occlusion tests and therapeutic vessel occlusions revisited: when, when
      not, and how.

PMID- 24457823
TI  - WEB-DL endovascular treatment of wide-neck bifurcation aneurysms: short- and
      midterm results in a European study.
AB  - BACKGROUND AND PURPOSE: Flow disruption with the WEB-DL device has been used
      safely for the treatment of wide-neck bifurcation aneurysms, but the stability of
      aneurysm occlusion after this treatment is unknown. This retrospective
      multicenter European study analyzed short- and midterm data in patients treated
      with WEB-DL. MATERIALS AND METHODS: Twelve European neurointerventional centers
      participated in the study. Clinical data and pre- and postoperative short- and
      midterm images were collected. An experienced interventional neuroradiologist
      independently analyzed the images. Aneurysm occlusion was classified into 4
      grades: complete occlusion, opacification of the proximal recess of the device,
      neck remnant, and aneurysm remnant. RESULTS: Forty-five patients (34 women and 11
      men) 35-74 years of age (mean, 56.3 +/- 9.6 years) with 45 aneurysms treated with
      the WEB device were included. Aneurysm locations were the middle cerebral artery
      in 26 patients, the posterior circulation in 13 patients, the anterior
      communicating artery in 5 patients, and the internal carotid artery terminus in 1
      patient. Forty-two aneurysms were unruptured. Good clinical outcome (mRS < 2) was
      observed in 93.3% of patients at the last follow-up. Adequate occlusion (complete
      occlusion, opacification of the proximal recess, or neck remnant) was observed in
      30/37 patients (81.1%) in short-term follow-up (median, 6 months) and in 26/29
      patients (89.7%) in midterm follow-up (median, 13 months). Worsening of the
      aneurysm occlusion was observed in 2/28 patients (7.1%) at midterm follow-up.
      CONCLUSIONS: The results suggest that the WEB endovascular treatment of wide-neck
      bifurcation aneurysms offers stable occlusion in a class of aneurysms that are
      historically unstable. Additionally, our data show that opacification of the WEB
      recess can be delineated from true neck or aneurysm remnants.

PMID- 24457825
TI  - Fertile approaches to dissecting mechanisms of premating and postmating
      prezygotic reproductive isolation.
AB  - In sexually reproducing organisms, speciation involves the evolution of
      mechanisms that confer reproductive isolation between diverging lineages. Here we
      discuss recent research on the molecular basis of traits that mediate these
      barriers during premating and postmating, prezygotic stages of reproduction. In
      some cases, the specific loci underlying the expression of reproductive barriers
      are known, most notably when premating isolation is due to flower color or scent
      differences, and when postmating isolation is due to divergent gamete signaling.
      In addition, emerging work in molecular biology and genomics is revealing the
      mechanistic basis of prezygotic reproductive traits within species, and therefore
      establishing clear candidates for future work examining their potential role in
      reproductive isolation between species. 

PMID- 24457826
TI  - Stabilized porous liposomes with encapsulated Gd-labeled dextran as a highly
      efficient MRI contrast agent.
AB  - A highly efficient contrast agent for magnetic resonance imaging was developed by
      encapsulating gadolinium within a stabilized porous liposome. The highly porous
      membrane leads to a high relaxivity of the encapsulated Gd. The stability of the
      liposome was improved by forming a polymer network within the bilayer membrane. 

PMID- 24457828
TI  - Bendamustine as monotherapy and in combination regimens for the treatment of
      chronic lymphocytic leukemia and non-hodgkin lymphoma: a retrospective analysis.
AB  - BACKGROUND/AIM: In this study, we carried out a retrospective analysis of the
      efficacy and toxicity of bendamustine in patients with B-cell lymphoproliferative
      diseases. METHODS: Bendamustine was administered both as monotherapy and in
      combined protocols to 92 patients, including 76 patients with chronic lymphocytic
      leukemia (CLL) and 16 patients with indolent lymphomas. Bendamustine plus
      rituximab was used to treat 65.2% of the patients, and 34.8% of the patients
      received bendamustine as monotherapy. RESULTS: The overall response rate was
      64.2%, including the complete response rate (18.5%) and the partial response rate
      (45.7%). The median overall survival (OS) was 11.5 months. Among the pretreatment
      parameters, beta2-microglobulin (RR = 1.413; p = 0.001) and hemoglobin levels (RR
      = 0.85; p = 0.03) significantly influenced survival. The OS was significantly
      longer in patients who received <=2 lines of previous therapy compared to >3
      lines (p = 0.043; log-rank test) and those who received >=4 courses of therapy
      with bendamustine (p = 0.0007; log-rank test). Toxicity was predominantly
      hematological, including grade III/IV neutropenia in 33.7%, thrombocytopenia in
      13%, and anemia in 13% of patients. CONCLUSION: Bendamustine, both in monotherapy
      and in combination regimens, is an effective therapy with a favorable toxicity
      profile in patients with indolent B-cell malignancies.

PMID- 24457829
TI  - Doping potassium ions in silver cyanide complexes for green luminescence.
AB  - Doping potassium ions in silver cyanide complexes leads to two heterometallic
      silver-potassium cyanide complexes, namely, [Me4N]2[KAg3(CN)6] (1) with a typical
      NaCl-type framework containing distinct ligand-unsupported argentophilic
      interactions, and [Ag3(H2O)3][K(CN)2]3 (2) with an unprecedented 3-D (4,4,6,6)
      connected framework formed by unique [Ag3(H2O)3] clusters connecting concave
      convex [K(CN)2] layers. The two complexes exhibit green luminescence, and the
      relationships between their structures and photoluminescence, as well as the
      regulating effect on the luminescence by doping of potassium ions are well
      investigated via density functional theory analysis.

PMID- 24457830
TI  - Electrodeposition technique-dependent photoelectrochemical and photocatalytic
      properties of an In2S3/TiO2 nanotube array.
AB  - Electrodeposition is a very versatile tool to fabricate multicomponent TiO2
      nanotube array (NTA) composites. However, the understanding of the correlation
      between the component structure and the fabrication technique has not been
      clearly investigated yet, though it has been observed that the performance of
      composites is bound up with the component structure. In this work, the
      photoelectrochemical properties of In2S3-TiO2 NTA composites prepared by CV
      electrodeposition, potentiostatic electrodeposition and pulse electrodeposition,
      respectively, were investigated. The results revealed that the as-prepared
      photoelectrodes exhibited electrodeposition technique-dependent properties, and
      the pulse prepared In2S3-TiO2 yielded the highest and stable photocurrent
      response, consequently exhibiting a superior photocatalytic activity in the
      degradation of p-nitrophenol (PNP). This may be attributed to the homogeneous,
      ultra-fine structure of In2S3 nanoparticles (NPs), which brings about a high
      charge separation efficiency. Furthermore, the trapping tests showed that both
      radicals and holes were the main active species in the photocatalytic degradation
      of PNP. This work not only provided a firm basis for maximizing photocatalytic
      activity via tuning fabrication techniques but also gave a deep insight into the
      photocatalytic mechanism. 

PMID- 24457827
TI  - NF-kappaB1 inhibits c-Myc protein degradation through suppression of FBW7
      expression.
AB  - NF-kappaB is a well-known transcription factor in regulation of multiple gene
      transcription and biological processes, and most of them are relied on its
      transcriptional activity of the p65/RelA subunit, while biological function of
      another ubiquitously expressed subunit NF-kappaB1 (p50) remains largely unknown
      due to lack transcriptional activation domain. Here we discovered a novel
      biological function of p50 as a regulator of oncogenic c-Myc protein degradation
      upon arsenite treatment in a NF-kappaB transcriptional-independent mechanism. Our
      results found that p50 was crucial for c-Myc protein induction following arsenite
      treatment by using specific knockdown and deletion of p50 in its normal expressed
      cells as well as reconstituting expression of p50 in its deficient cells.
      Subsequently we showed that p50 upregulated c-Myc protein expression mainly
      through inhibiting its degradation. We also identified that p50 exhibited this
      novel property by suppression of FBW7 expression. FBW7 was profoundly upregulated
      in p50-deficient cells in comparison to that in p50 intact cells, whereas
      knockdown of FBW7 in p50-/- cells restored arsenite-induced c-Myc protein
      accumulation, assuring that FBW7 up-regulation was responsible for defect of c
      Myc protein expression in p50-/- cells. In addition, we discovered that p50
      suppressed fbw7 gene transcription via inhibiting transcription factor E2F1
      transactivation. Collectively, our studies demonstrated a novel function of p50
      as a regulator of c-Myc protein degradation, contributing to our notion that p50
      regulated protein expression through multiple levels at protein translation and
      degradation, further providing a significant insight into the understanding of
      biomedical significance of p50 protein.

PMID- 24457831
TI  - Improved electron transfer and plasmonic effect in dye-sensitized solar cells
      with bi-functional Nb-doped TiO2/Ag ternary nanostructures.
AB  - TiO2 nanoparticles are surface-modified via atom transfer radical polymerization
      (ATRP) with a hydrophilic poly(oxyethylene)methacrylate (POEM), which can
      coordinate to the Ag precursor, i.e. silver trifluoromethanesulfonate (AgCF3SO3).
      Following the reduction of Ag ions, a Nb2O5 doping process and calcination at 450
      degrees C, bi-functional Nb-doped TiO2/Ag ternary nanostructures are generated.
      The resulting nanostructures are characterized by energy-filtering transmission
      electron microscopy (EF-TEM), X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), and UV-visible spectroscopy. The dye-sensitized solar cell
      (DSSC) based on the Nb-doped TiO2/Ag nanostructure photoanode with a polymerized
      ionic liquid (PIL) as the solid polymer electrolyte shows an overall energy
      conversion efficiency (eta) of 6.9%, which is much higher than those of neat TiO2
      (4.7%) and Nb-doped TiO2 (5.4%). The enhancement of eta is mostly due to the
      increase of current density, attributed to the improved electron transfer
      properties including electron injection, collection, and plasmonic effects
      without the negative effects of charge recombination or problems with corrosion.
      These properties are supported by intensity modulated photocurrent/voltage
      spectroscopy (IMPS/IMVS) and incident photon-to-electron conversion efficiency
      (IPCE) measurements. 

PMID- 24457832
TI  - Biomarkers for the early detection of anthracycline-induced cardiotoxicity:
      current status.
AB  - BACKGROUND: Cardiotoxicity is a well-known and potentially serious complication
      of anticancer therapy. Anthracycline-based chemotherapy represents the greatest
      risk. Early detection of cardiotoxicity is crucial for applying preventive and
      supportive therapeutic strategies. METHODS AND RESULTS: Various methods have been
      recommended for monitoring of cardiotoxicity. In our conditions, echocardiography
      and electrocardiography are routinely used. However, this approach shows low
      sensitivity for the early prediction of cardiomyopathy when the possibilities of
      appropriate management could still improve the patient's outcome. Recently,
      biomarkers of cardiac injury have been investigated in the assessment of
      chemotherapy-induced cardiotoxicity. Cardiospecific biomarkers, such as cardiac
      troponins, show high diagnostic efficacy in the early subclinical phase of the
      disease before the clinical onset of cardiomyopathy. Increase in their
      concentrations correlates with disease severity. As for natriuretic peptides,
      some studies, including ours, have shown promising results. Definitive evidence
      of their diagnostic and prognostic role in this context is still lacking and
      natriuretic peptides have not been routinely used for monitoring of
      cardiotoxicity in clinical practice. Other perspective biomarkers of
      cardiotoxicity in oncology are under study, especially heart-type fatty acid
      binding protein (H-FABP) and glycogen phosphorylase BB (GPBB). Our studies using
      GPBB have provided encouraging results. However, the available data are limited
      and their practical use in this context cannot be recommended until their
      clinical efficacy is clearly defined. CONCLUSIONS: This review covers the current
      status of biomarkers for the early detection of anthracycline-induced
      cardiotoxicity. The authors present in brief, their own experience with multiple
      biomarkers in the detection of cardiotoxicity.

PMID- 24457833
TI  - Breast cancer detection using combined curvelet based enhancement and a novel
      segmentation methods.
AB  - AIM: This paper describes the digital implementation of a mathematical transform
      namely 2D Fast Discrete Curvelet Transform (FDCT) via UnequiSpaced Fast Fourier
      Transform (USFFT) in combination with the novel segmentation method for effective
      detection of breast cancer. METHODS: USFFT performs exact reconstructions with
      high image clarity. Radon, ridgelet and Cartesian filters are included in this
      method. Mean Square Error (MSE) and Peak Signal to Noise Ratio (PSNR) were
      calculated for the image and the resulting value showed that the proposed method
      performs well on mammogram image in reducing noise with good extraction of edges.
      This work includes a novel segmentation method, which combines Modified Local
      Range Modification (MLRM) and Laplacian of Gaussian (LoG) edge detection method
      to segment the textured features in the mammogram image. RESULTS: The result was
      analyzed using a Receiver Operating Characteristics (ROC) plot and the detection
      accuracy found was 99% which is good compared to existing methods.

PMID- 24457834
TI  - Unstable angina pectoris prior to ST elevation myocardial infarction in patients
      treated with primary percutaneous coronary intervention has no influence on
      prognosis.
AB  - BACKGROUND: Pre-infarction unstable angina pectoris (UAP) can be considered
      ischemic preconditioning. The aim of this study was to compare short and long
      term outcomes in patients with or without pre-infarction UAP and ST elevation
      myocardial infarction (STEMI) treated with primary percutaneous coronary
      intervention (PCI). METHODS: 593 patients with STEMI (388 without and 205 with
      UAP) were evaluated. Levels of biomarkers (troponin I, BNP, NT-ProBNP, neopterin,
      endoglin and pentraxin-3) at hospital admission and 24 h after STEMI onset were
      assessed. Echocardiography was undertaken on the fourth day after MI and after 12
      months. The median follow-up was 37 months. RESULTS: We found no significant
      differences in sex, age or risk factors for atherosclerosis between the UAP and
      non-UAP group. As the median time from the onset of chest pain to admission was
      significantly longer in the UAP group (228 min vs 258 min; P=0.009), we used a
      propensity score to obtain comparable matched groups for use in further analyses.
      The levels of NT-proBNP were significantly higher on admission and after 24 hours
      in the UAP group. Left ventricular functions according to invasive and
      echocardiographic parameters were entirely comparable at hospitalization and
      after 12 months. No differences were found in severity index of acute heart
      failure during hospitalization. The incidence of major acute coronary events
      during follow-up was comparable for the groups. CONCLUSIONS: In patients with
      STEMI treated with primary PCI, pre-infarction UAP has no beneficial clinical
      effect during hospitalization or during long-term follow-up.

PMID- 24457835
TI  - miR-888: hit it when you see it!

PMID- 24457836
TI  - In vitro and in vivo repair activities of undifferentiated and classically and
      alternatively activated macrophages.
AB  - OBJECTIVE: Macrophages play a critical role in wound repair. However, the
      specific role of the different macrophage subtypes in wound repair remains
      incompletely understood. The aim of this study was to compare the wound repair
      activities of undifferentiated macrophages (M0), classically activated
      macrophages (M1) and alternatively activated (M2) macrophages. METHODS: The
      macrophage repair activities of intestinal wounds were evaluated using in vitro
      and in vivo models. RESULTS: All three macrophage subtypes enhanced wound closure
      in vitro, with the M2 macrophages demonstrating greater repair activities than
      the M0 and M1 macrophages. Injection of M0 and M2 macrophages into mice with
      experimental dextran sodium sulfate-induced colitis significantly enhanced ulcer
      repair when compared to control mice. In contrast, injection of M1 macrophages
      did not affect ulcer repair. CONCLUSIONS: These results underscore the wound
      repair capacity of different macrophage subsets. Notably, wound repair activity
      is not restricted to M2 macrophages, as the current literature suggests.

PMID- 24457837
TI  - A rare complex chromosomal rearrangement in an oligospermic male: a case report
      and review of the Chinese literature.

PMID- 24457839
TI  - Bactericidal/permeability-increasing protein originates in both the testis and
      the epididymis and localizes in mouse spermatozoa.
AB  - Bactericidal/permeability-increasing protein (BPI) is an endogenous antibiotic
      protein with activity against gram-negative bacteria. In the present study, we
      examined the expression of BPI in postnatal mouse testes and epididymides as well
      as the subcellular localization within epididymal spermatozoa. Our results showed
      that, BPI mRNA was expressed in testis and epididymis independently. Throughout
      the epididymis, the BPI protein level gradually decreased in the epididymal
      epithelium in a spatial manner, specialized within the cytoplasm of clear cells
      in the cauda part. We detected BPI proteins in intact acrosome, implying its
      testicular origin; on the other hand, after the acrosome reaction, BPI proteins
      were observed dispersed across the entire sperm head, especially enriched at the
      equatorial segment. Our findings suggested a dual origin of the BPI that
      generated both in the testis and epididymis, and associated with mouse
      spermatozoa. BPI protein might be involved in the dynamics modification of the
      sperm plasma membrane and also the fertilization process.

PMID- 24457838
TI  - Androgen effects on skeletal muscle: implications for the development and
      management of frailty.
AB  - Androgens have potent anabolic effects on skeletal muscle and decline with age in
      parallel to losses in muscle mass and strength. This loss of muscle mass and
      function, known as sarcopenia, is the central event in development of frailty,
      the vulnerable health status that presages adverse outcomes and rapid functional
      decline in older adults. The potential role of falling androgen levels in the
      development of frailty and their utility as function promoting therapies in older
      men has therefore attracted considerable attention. This review summarizes
      current concepts and definitions in muscle ageing, sarcopenia and frailty, and
      evaluates recent developments in the study of androgens and frailty. Current
      evidence from observational and interventional studies strongly supports an
      effect of androgens on muscle mass in ageing men, but effects on muscle strength
      and particularly physical function have been less clear. Androgen treatment has
      been generally well-tolerated in studies of older men, but concerns remain over
      higher dose treatments and use in populations with high cardiovascular risk. The
      first trials of selective androgen receptor modulators (SARMs) suggest similar
      effects on muscle mass and function to traditional androgen therapies in older
      adults. Important future directions include the use of these agents in
      combination with exercise training to promote functional ability across different
      populations of older adults, as well as more focus on the relationships between
      concurrent changes in hormone levels, body composition and physical function in
      observational studies.

PMID- 24457840
TI  - Sex steroids and glucose metabolism.
AB  - Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes
      mellitus (T2DM) and also predict the onset of these adverse metabolic states.
      Body composition (body mass index, waist circumference) is an important mediator
      of this relationship. Sex hormone binding globulin is also inversely associated
      with insulin resistance and T2DM but the data regarding estrogen are
      inconsistent. Clinical models of androgen deficiency including Klinefelter's
      syndrome and androgen deprivation therapy in the treatment of advanced prostate
      cancer confirm the association between androgens and glucose status. Experimental
      manipulation of the insulin/glucose milieu and suppression of endogenous
      testicular function suggests the relationship between androgens and insulin
      sensitivity is bidirectional. Androgen therapy in men without diabetes is not
      able to differentiate the effect on insulin resistance from that on fat mass, in
      particular visceral adiposity. Similarly, several small clinical studies have
      examined the efficacy of exogenous testosterone in men with T2DM, however, the
      role of androgens, independent of body composition, in modifying insulin
      resistance is uncertain.

PMID- 24457841
TI  - Differential expression of 5-alpha reductase isozymes in the prostate and its
      clinical implications.
AB  - The development of human benign or malignant prostatic diseases is closely
      associated with androgens, primarily testosterone (T) and dihydrotestosterone
      (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential
      expression of 5-AR isozymes is observed in both human benign and malignant
      prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of
      benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive
      agents for prostate cancer (PCa). This review discusses the role of the
      differential expression of 5-AR in the normal development of the human prostate
      and in the pathogenesis and progression of BPH and PCa.

PMID- 24457842
TI  - Separation of photo-induced radical pair in cryptochrome to a functionally
      critical distance.
AB  - Cryptochrome is a blue light receptor that acts as a sensor for the geomagnetic
      field and assists many animals in long-range navigation. The magnetoreceptor
      function arises from light-induced formation of a radical pair through electron
      transfer between a flavin cofactor (FAD) and a triad of tryptophan residues.
      Here, this electron transfer is investigated by quantum chemical and classical
      molecular dynamics calculations. The results reveal how sequential electron
      transfer, assisted by rearrangement of polar side groups in the cryptochrome
      interior, can yield a FAD-Trp radical pair state with the FAD and Trp partners
      separated beyond a critical distance. The large radical pair separation reached
      establishes cryptochrome's sensitivity to the geomagnetic field through weakening
      of distance-dependent exchange and dipole-dipole interactions. It is estimated
      that the key secondary electron transfer step can overcome in speed both
      recombination (electron back-transfer) and proton transfer involving the radical
      pair reached after primary electron transfer. 

PMID- 24457843
TI  - Meal duration as a measure of orofacial nociceptive responses in rodents.
AB  - A lengthening in meal duration can be used to measure an increase in orofacial
      mechanical hyperalgesia having similarities to the guarding behavior of humans
      with orofacial pain. To measure meal duration unrestrained rats are continuously
      kept in sound attenuated, computerized feeding modules for days to weeks to
      record feeding behavior. These sound-attenuated chambers are equipped with chow
      pellet dispensers. The dispenser has a pellet trough with a photobeam placed at
      the bottom of the trough and when a rodent removes a pellet from the feeder
      trough this beam is no longer blocked, signaling the computer to drop another
      pellet. The computer records the date and time when the pellets were taken from
      the trough and from this data the experimenter can calculate the meal parameters.
      When calculating meal parameters a meal was defined based on previous work and
      was set at 10 min (in other words when the animal does not eat for 10 min that
      would be the end of the animal's meal) also the minimum meal size was set at 3
      pellets. The meal duration, meal number, food intake, meal size and inter-meal
      interval can then be calculated by the software for any time period that the
      operator desires. Of the feeding parameters that can be calculated meal duration
      has been shown to be a continuous noninvasive biological marker of orofacial
      nociception in male rats and mice and female rats. Meal duration measurements are
      quantitative, require no training or animal manipulation, require cortical
      participation, and do not compete with other experimentally induced behaviors.
      These factors distinguish this assay from other operant or reflex methods for
      recording orofacial nociception. 

PMID- 24457844
TI  - The mechanistic approach of The Theory of Island Biogeography and its current
      relevance.
AB  - Philosophers of science have examined The Theory of Island Biogeography by Robert
      MacArthur and E. O. Wilson (1967) mainly due to its important contribution to
      modeling in ecology, but they have not examined it as a representative case of
      ecological explanation. In this paper, I scrutinize the type of explanation used
      in this paradigmatic work of ecology. I describe the philosophy of science of
      MacArthur and Wilson and show that it is mechanistic. Based on this account and
      in light of contributions to the mechanistic conception of explanation due to
      Craver (2007), and Bechtel and Richardson (1993), I argue that MacArthur and
      Wilson use a mechanistic approach to explain the species-area relationship. In
      light of this examination, I formulate a normative account of mechanistic
      explanation in ecology. Furthermore, I argue that it offers a basis for
      methodological unification of ecology and solves a dispute on the nature of
      ecology. Lastly, I show that proposals for a new paradigm of biogeography appear
      to maintain the norms of mechanistic explanation implicit in The Theory of Island
      Biogeography. 

PMID- 24457845
TI  - Overview of MS spasticity.

PMID- 24457846
TI  - THC:CBD spray and MS spasticity symptoms: data from latest studies.
AB  - New clinical experience with 9-delta-tetrahydocannabinol (THC) and cannabidiol
      (CBD) oromucosal spray (Sativex(r)) involving more than an additional 1,000
      patients with MS spasticity (approximately 150 in clinical studies and 900 in
      post-marketing surveillance studies) have become available in 2013 and are
      reviewed. A randomized, placebo controlled long-term follow-up clinical trial
      with THC:CBD spray versus placebo demonstrated that it was not associated with
      cognitive decline, depression or significant mood changes after 12 months of
      treatment. Furthermore, in a prospective observational pilot study involving 33
      patients (60% female) aged 33-68 years and a mean disease duration of 6.6 years,
      THC:CBD oromucosal spray did not adversely influence standard driving ability in
      patients with moderate to severe MS spasticity. Other new long term observational
      data about the use of THC:CBD oromucosal spray in clinical practice are available
      from patient registries in the UK, Germany and Spain. Findings to date reinforce
      the efficacy and safety observed in Phase III clinical trials. It is of interest
      that in practice average dosages used by patients tended to be lower than those
      reported in clinical studies (5-6.4 vs. >8 sprays/day), and effectiveness was
      maintained in the majority of patients. Importantly, no additional safety
      concerns were identified in the registry studies which included findings from
      patients who have been treated for prolonged periods (in the German/UK registry
      45% of patients had >2 years exposure). Thus, these new data support a positive
      benefit-risk relationship for THC:CBD oromucosal spray during longer-term use.

PMID- 24457847
TI  - Who benefits most from THC:CBD spray? Learning from clinical experience.
AB  - Patients with multiple sclerosis (MS) represent a diverse and heterogeneous
      population varying in terms of disease type, its severity and variable
      progression/time-course, and with regard to the wide range of presenting
      symptoms. Consequently, detailed experience with individual patients is important
      to provide examples of therapy to specific patient types. In this article, real
      life data from clinical practice showing specific aspects relating to use of 9
      delta-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex(r))
      in patients with moderate to severe spasticity resistant to usual therapy will be
      presented. Three common clinical scenarios will be considered: MS patients with
      resistance to usual spasticity therapies; patients with impairment in MS
      spasticity symptoms; MS patients with relevant impairment in quality of
      life/activities of daily living (QoL/ADL). These case reports highlight the
      diverse nature of the MS spasticity population and they show the possible
      usefulness of THC:CBD oromucosal spray in individual patients with moderate to
      severe spasticity resistant to existing therapies, within the frame of use
      approved after large clinical trial results. Perhaps the most important finding
      is the possibility of obtaining relevant improvements in QoL/ADL in some patients
      with resistant MS spasticity, allowing them to engage back in physical and social
      activities.

PMID- 24457848
TI  - Taking a life.

PMID- 24457849
TI  - Prosthetics: galvanic effect.

PMID- 24457850
TI  - NHS dentistry: a serious shift.

PMID- 24457851
TI  - Diabetes: multi-disciplinary approaches.

PMID- 24457852
TI  - Fluoridation: advocating public health measures.

PMID- 24457853
TI  - Teaching stress management.

PMID- 24457854
TI  - Investigation: NHS Choices - three years on.

PMID- 24457860
TI  - A dentist's life: Fix teeth. Moan. Go home. Interview by Kate Quinlan.

PMID- 24457862
TI  - In the news: antibiotic resistance.

PMID- 24457864
TI  - Ethical responsibility and treatment errors.
AB  - Error disclosure is an important part of a healthcare provider's job. In a system
      such as healthcare, it is inevitable that mistakes will be made and that patients
      will suffer unnecessarily. Knowing this raises many questions. How does one
      determine when and how much to disclose? Is there such a thing as too much
      honesty? With all of the conflicting ideas about when, where, how and what to
      disclose, how can a provider decide for him or herself how to handle each
      situation? And should the provider be held responsible for the error or should
      the system or the patient accept some of the blame in many cases? This article
      will explore the factors influencing how errors are disclosed and will discuss
      the idea of responsibility in medical care and error disclosure. 

PMID- 24457865
TI  - The management of severe hypodontia. Part 2: bone augmentation and the provision
      of implant supported prostheses.
AB  - The first part of this series on severe hypodontia discussed the assessment of
      patients and factors to consider when treatment planning for the provision of
      conventional restorative solutions. This article discusses the provision of
      implant supported prostheses in the severe hypodontia patient who typically
      presents with inadequate bone volume and other associated dental and craniofacial
      anomalies. The role of bone augmentation to facilitate implant placement is
      discussed, in addition to prosthesis design and long-term maintenance. With
      careful case selection and planning most patients with severe hypodontia can be
      rehabilitated effectively, both functionally and aesthetically, with implant
      supported prostheses. In complex cases the involvement of a multidisciplinary
      team is needed to improve outcome. It should be highlighted that these patients
      will require ongoing follow up, maintenance and retreatment procedures over their
      lifetimes. 

PMID- 24457866
TI  - Transient facial nerve paralysis (Bell's palsy) following administration of
      hepatitis B recombinant vaccine: a case report.
AB  - Bell's palsy is the sudden onset of unilateral transient paralysis of facial
      muscles resulting from dysfunction of the seventh cranial nerve. Presented here
      is a 26-year-old female patient with right lower motor neurone facial palsy
      following hepatitis B vaccination. Readers' attention is drawn to an uncommon
      cause of Bell's palsy, as a possible rare complication of hepatitis B
      vaccination, and steps taken to manage such a presentation. 

PMID- 24457867
TI  - A case report looking at ACE inhibitors as the cause of angioedema during dental
      treatment.
AB  - Angiotensin converting enzymes, also known as ACE inhibitors are regularly
      prescribed by doctors in the treatment of congestive heart failure and
      hypertension. In this case report, we will be looking at the delayed onset of
      angioedema as a result of ACE inhibitors that occurred during dental treatment.
      We will discuss other causes of angioedema and its management and aim to raise
      awareness among clinicians to include this in their differential diagnosis of
      swellings around the mouth, particularly as it can mimic the initial response or
      be a prelude to an anaphylactic shock. 

PMID- 24457872
TI  - Summary of: fluoride intake of infants living in non-fluoridated and fluoridated
      areas.
AB  - OBJECTIVES: Data on fluoride exposure of infants are sparse. This study aimed to
      estimate total daily fluoride intake (TDFI) of infants aged 1-12 months, living
      in non-fluoridated and fluoridated areas in north-east England. METHODS: Daily
      dietary fluoride intake was assessed using a three-day food diary coupled with
      analysis of fluoride content of food/drink consumed, using a F-ISE and diffusion
      method. A questionnaire with an interview was used to collect information on
      toothbrushing habits. TDFI was estimated from diet, plus fluoride supplements and
      dentifrice ingestion where used. RESULTS: Thirty-eight infants completed the
      study; 19 receiving fluoridated water (mean 0.97 mgF/l) and 19 receiving non
      fluoridated water (mean 0.19 mgF/l). Mean (SD) TDFI for the infants living in
      fluoridated and non-fluoridated areas was 0.107 (0.054) and 0.024 (0.015) mg/kg
      body weight per day, respectively. Diet was the only fluoride source for 87% of
      infants and none used fluoride supplements. For infants for whom mouth/teeth
      cleaning was undertaken, dentifrice contribution to TDFI ranged from 24 to 78%.
      CONCLUSIONS: Infants living in fluoridated areas, in general, may receive a
      fluoride intake, from diet only, of more than the suggested optimal range for
      TDFI. This emphasises the importance of estimating TDFI at an individual level
      when recommendations for fluoride use are being considered.

PMID- 24457873
TI  - Summary of: dental composite materials and renal function in children.
AB  - OBJECTIVE: To examine whether greater exposure to resin-based composite
      materials, which may intra-orally release bisphenol A (BPA), is associated with
      worse renal function outcomes in children. DESIGN: Prospective multi-centre
      study. SETTING: Community health dental clinics in Boston and Maine from 1997
      2005. SUBJECTS AND METHODS: Five hundred and thirty-four New England Children's
      Amalgam Trial participants aged six to ten years were randomised to treatment
      with amalgam or resin-based composite restorations over five years of follow-up.
      INTERVENTIONS: Restorations were placed according to treatment arm, and sealants
      placed per standard of care. Cumulative composite exposure was calculated using
      surface-years (each treated surface weighted by number years present). MAIN
      OUTCOME MEASURES: Urinary excretion of albumin, gamma-glutamyl transpeptidase
      (gamma-GT), and N-acetyl-beta-D-glucosaminidase (NAG) were available for 417
      children. RESULTS: Analysis of covariance showed no association between exposure
      to dental composites, polyacid-modified compomer, or flowable composite dental
      sealants and preventative resin restorations with levels of renal function. There
      was no association between composite materials and thresholds indicating renal
      damage in logistic regression models. CONCLUSIONS: This study found no harmful
      associations between dental composite materials and renal function in children.
      Therefore, concerns about renal function need not be a consideration in the
      choice of dental restoration material or placement of preventative dental
      sealants.

PMID- 24457874
TI  - The 'Dental Institution' in London, 1817-21. A prototype dental school: the
      vision of Levi Spear Parmly.
AB  - This paper explores Levi Spear Parmly's vision for the education of dentists in
      the early nineteenth century and how his work impacted on Anglo-American dental
      schools. 

PMID- 24457892
TI  - Fluoride intake of infants living in non-fluoridated and fluoridated areas.
AB  - OBJECTIVES: Data on fluoride exposure of infants are sparse. This study aimed to
      estimate total daily fluoride intake (TDFI) of infants aged 1-12 months, living
      in non-fluoridated and fluoridated areas in north-east England. METHODS: Daily
      dietary fluoride intake was assessed using a three-day food diary coupled with
      analysis of fluoride content of food/drink consumed, using a F-ISE and diffusion
      method. A questionnaire with an interview was used to collect information on
      toothbrushing habits. TDFI was estimated from diet, plus fluoride supplements and
      dentifrice ingestion where used. RESULTS: Thirty-eight infants completed the
      study; 19 receiving fluoridated water (mean 0.97 mgF/l) and 19 receiving non
      fluoridated water (mean 0.19 mgF/l). Mean (SD) TDFI for the infants living in
      fluoridated and non-fluoridated areas was 0.107 (0.054) and 0.024 (0.015) mg/kg
      body weight per day, respectively. Diet was the only fluoride source for 87% of
      infants and none used fluoride supplements. For infants for whom mouth/teeth
      cleaning was undertaken, dentifrice contribution to TDFI ranged from 24 to 78%.
      CONCLUSIONS: Infants living in fluoridated areas, in general, may receive a
      fluoride intake, from diet only, of more than the suggested optimal range for
      TDFI. This emphasises the importance of estimating TDFI at an individual level
      when recommendations for fluoride use are being considered.

PMID- 24457894
TI  - Spray coating of superhydrophobic and angle-independent coloured films.
AB  - Angle-independent coloured films with superhydrophobicity were fabricated from
      quasi-amorphous arrays of monodispersed fluorinated silica nanoparticles via one
      step spray coating. The film exhibited a high contact angle (>150 degrees ) and a
      low roll-off angle (~2 degrees ) and the colour could be tuned to blue, green and
      moccasin by varying the size of the nanoparticles.

PMID- 24457893
TI  - Dental composite materials and renal function in children.
AB  - OBJECTIVE: To examine whether greater exposure to resin-based composite
      materials, which may intra-orally release bisphenol A (BPA), is associated with
      worse renal function outcomes in children. DESIGN: Prospective multi-centre
      study. SETTING: Community health dental clinics in Boston and Maine from 1997
      2005.Subjects and methods Five hundred and thirty-four New England Children's
      Amalgam Trial participants aged six to ten years were randomised to treatment
      with amalgam or resin-based composite restorations over five years of follow-up.
      INTERVENTIONS: Restorations were placed according to treatment arm, and sealants
      placed per standard of care. Cumulative composite exposure was calculated using
      surface-years (each treated surface weighted by number years present). MAIN
      OUTCOME MEASURES: Urinary excretion of albumin, gamma-glutamyl transpeptidase
      (gamma-GT), and N-acetyl-beta-D-glucosaminidase (NAG) were available for 417
      children. RESULTS: Analysis of covariance showed no association between exposure
      to dental composites, polyacid-modified compomer, or flowable composite dental
      sealants and preventative resin restorations with levels of renal function. There
      was no association between composite materials and thresholds indicating renal
      damage in logistic regression models. CONCLUSIONS: This study found no harmful
      associations between dental composite materials and renal function in children.
      Therefore, concerns about renal function need not be a consideration in the
      choice of dental restoration material or placement of preventative dental
      sealants.

PMID- 24457895
TI  - The role of laryngoscopy in the diagnosis of spasmodic dysphonia.
AB  - IMPORTANCE: Spasmodic dysphonia (SD) can be difficult to diagnose, and patients
      often see multiple physicians for many years before diagnosis. Improving the
      speed of diagnosis for individuals with SD may decrease the time to treatment and
      improve patient quality of life more quickly. OBJECTIVE: To assess whether the
      diagnosis of SD can be accurately predicted through auditory cues alone without
      the assistance of visual cues offered by laryngoscopic examination. DESIGN,
      SETTING, AND PARTICIPANTS: Single-masked, case-control study at a specialized
      referral center that included patients who underwent laryngoscopic examination as
      part of a multidisciplinary workup for dysphonia. Twenty-two patients were
      selected in total: 10 with SD, 5 with vocal tremor, and 7 controls without SD or
      vocal tremor. INTERVENTIONS: The laryngoscopic examination was recorded,
      deidentified, and edited to make 3 media clips for each patient: video alone,
      audio alone, and combined video and audio. These clips were randomized and
      presented to 3 fellowship-trained laryngologist raters (A.D.R., A.T.H., and
      A.M.K.), who established the most probable diagnosis for each clip. Intrarater
      and interrater reliability were evaluated using repeat clips incorporated in the
      presentations. MAIN OUTCOMES AND MEASURES: We measured diagnostic accuracy for
      video-only, audio-only, and combined multimedia clips. These measures were
      established before data collection. Data analysis was accomplished with analysis
      of variance and Tukey honestly significant differences. RESULTS: Of patients with
      SD, diagnostic accuracy was 10%, 73%, and 73% for video-only, audio-only, and
      combined, respectively (P < .001, df = 2). Of patients with vocal tremor,
      diagnostic accuracy was 93%, 73%, and 100% for video-only, audio-only, and
      combined, respectively (P = .05, df = 2). Of the controls, diagnostic accuracy
      was 81%, 19%, and 62% for video-only, audio-only, and combined, respectively (P <
      .001, df = 2). CONCLUSIONS AND RELEVANCE: The diagnosis of SD during examination
      is based primarily on auditory cues. Viewing combined audio and video clips
      afforded no change in diagnostic accuracy compared with audio alone. Laryngoscopy
      serves an important role in the diagnosis of SD by excluding other pathologic
      causes and identifying vocal tremor.

PMID- 24457896
TI  - Two potential therapeutic antibodies bind to a peptide segment of membrane-bound
      IgE in different conformations.
AB  - IgE mediates hypersensitivity reactions responsible for most allergic diseases,
      which affect 20-40% of the population in developed countries. A 52-residue domain
      of membrane-bound IgE (mIgE) called CepsilonmX is currently a target for
      developing therapeutic antibodies; however, its structure is unknown. Here we
      show that two antibodies with therapeutic potential in IgE-mediated allergic
      diseases, which can cause cytolytic effects on mIgE-expressing B lymphocytes and
      downregulate IgE production, target different conformations of an intrinsically
      disordered region (IDR) in the extracellular CepsilonmX domain. We provide an
      important example of antibodies targeting an extracellular IDR of a receptor on
      the surface of intended target cells. We also provide fundamental structural
      characteristics unique to human mIgE, which may stimulate further studies to
      investigate whether other monoclonal antibodies (mAbs) targeting intrinsically
      disordered peptide segments or vaccine-like products targeting IDRs of a membrane
      protein can be developed. 

PMID- 24457897
TI  - Reply: To PMID 23807189.

PMID- 24457898
TI  - Autoimmune aspects of type 2 diabetes mellitus - a mini-review.
AB  - Autoimmunity is a well-known pathogenic component in type 1 diabetes (T1DM). The
      assumption that the pathogenesis of type 2 diabetes (T2DM) also encompasses
      autoimmune aspects is recognized increasingly, based on the presence of
      circulating autoantibodies against beta cells, self-reactive T cells, but also on
      the glucose-lowering efficacy of some immunomodulatory therapies in T2DM. The
      identification of these autoantibodies in elderly patients with slowly
      progressive manifestation of diabetes led to the introduction of a distinct
      clinical entity termed latent autoimmune diabetes of the adult (LADA), which
      combines features of both T1DM and T2DM. The autoantibody cluster differs in
      patients with LADA from patients with T1DM, but their presence indicates steady
      progression towards beta-cell death and subsequent need for initiation of insulin
      treatment in a shorter period of time compared to autoantibody-negative T2DM
      patients. Autoimmune aspects in T2DM are not solely restricted to autoantibodies
      and thus LADA. They include the self-reactive T cells or defects in regulatory T
      cells (Tregs), which have been detected in autoantibody-negative T2DM patients as
      well. One contributor to the autoimmune activation in T2DM seems to be the
      chronic inflammatory state, characteristic of this disease. Upon inflammation
      induced tissue destruction, cryptic 'self' antigens can trigger an autoimmune
      response, which in turn accelerates beta-cell death. Both innate and adaptive
      immune system components, specifically macrophages and self-reactive T cells,
      contribute to an increased secretion of inflammatory cytokines involved in
      inflammatory and autoimmune processes. However, the extent to which inflammation
      overlaps with autoimmunity is not known. Our review focuses on autoimmune
      involvement in T2DM, with an emphasis on LADA and the humoral immune response, on
      the involvement of chronic inflammation in autoimmunity, and specifically the
      role of B and T cells as links between inflammatory and autoimmune reactions. We
      will further stress the consequences of autoimmune activation for T2DM patients
      and present novel therapeutic approaches for T2DM management that rely on immune
      modulation.

PMID- 24457899
TI  - At high risk and want to quit: marijuana use among adults with depression or
      serious psychological distress.
AB  - OBJECTIVES: This study compared marijuana use characteristics and quit behaviors
      between adults with and without depression or serious psychological distress
      (SPD). METHODS: Drawing data for 39,133 non-institutionalized adults from the
      2011 National Survey on Drug Use and Health, we assessed marijuana use status,
      frequent use, dependence or abuse, and quit behaviors in association with
      lifetime clinician-identified depression, lifetime and recent major depressive
      episode (MDE), and recent SPD. RESULTS: Adults with depression or SPD were at a
      significantly higher risk of being lifetime ever users (OR=1.60-2.08), past year
      users (OR=1.67-1.86), frequent users (OR=1.40-1.62), and dependent or abusing
      users (OR=2.32-3.05) compared with adults without these symptoms. Adults with
      depression or SPD had a lower quit ratio overall, but were equally or even more
      likely to make quit or self-regulation attempts. Further analysis suggested that
      adults with recent MDE had the greatest level of quit attempts or self-regulation
      attempts compared with adults without MDE or with past MDE. CONCLUSIONS: These
      findings highlight the need for tailored cessation programs to sustain quit
      attempts and promote successful quitting among adults with depression or SPD,
      especially those with recent symptoms.

PMID- 24457900
TI  - Patterns and correlates of polytobacco use in the United States over a decade:
      NSDUH 2002-2011.
AB  - BACKGROUND: Few studies have examined the patterns and correlates of polytobacco
      use among a large, nationally representative population over an extended period
      of time. METHODS: This study examined 10years of data from the National Survey on
      Drug Use and Health (NSDUH) to establish time trends and correlates for exclusive
      and mixed use of cigarettes, smokeless tobacco (SLT), cigars, and pipes. RESULTS:
      Results show that rates of polytobacco use were essentially unchanged from 2002
      to 2011 (8.7% to 7.4%), though some product combinations, including cigarettes
      and SLT, cigars and SLT, and use of more than two products have increased. In
      tobacco users under age 26, the proportion of polytobacco use increased, even as
      overall tobacco use declined. The factors associated with polytobacco use among
      tobacco users included sex, income, education, risk taking/seeking behaviors, and
      outward indicators of 'risk-liability'. CONCLUSIONS: Findings provide a snapshot
      of trends of single and polytobacco product use as well as trends in combinations
      of product use. Longitudinal studies are needed to examine the sequence of
      individual patterns of tobacco product use and to identify whether polytobacco
      use results in greater nicotine dependence, increased exposure to harmful and
      potentially harmful constituents and/or greater risk of tobacco related disease.

PMID- 24457901
TI  - The effect of successful and unsuccessful smoking cessation on short-term
      anxiety, depression, and suicidality.
AB  - Research on the mental health effects of quitting smoking is limited. Smokers
      with mental illness appear to be at a higher risk of unsuccessful smoking
      cessation. Recent work suggests they are at elevated risk for post-cessation
      increases in anxiety, depression and suicidal ideation. The current study tested
      the effects of successful and unsuccessful smoking cessation on short-term
      psychopathology in 192 community participants. Smoking cessation outcomes were
      classified using expired carbon monoxide levels that were taken at quit week, 1
      and 2 week follow-up and 1 month follow-up. We found no psychopathology increases
      in participants who successfully quit smoking. For individuals struggling to quit
      our results partially supported a recently proposed struggling quitters
      hypothesis. However, the vast majority of individuals posited to be vulnerable by
      the struggling quitters hypothesis did not experience clinically significant
      increases in psychopathology. These findings have implications for clinicians
      whose clients are interested in smoking cessation.

PMID- 24457903
TI  - Coordination and conformational isomers in mononuclear iron complexes with
      pertinence to the [FeFe] hydrogenase active site.
AB  - A series of six mononuclear iron complexes of the type [Fe(X
      bdt)(P(R)2N(Ph)2)(CO)] (P(R)2N(Ph)2 = 1,5-diaza-3,7-diphosphaoctane, bdt =
      benzenedithiolate with X = H, Cl2 or Me and R = Ph, Bn, Cyc or tert-Bu) was
      prepared. This new class of penta-coordinate iron complexes contains a free
      coordination site and a pendant base as essential structural features of the
      [FeFe]-hydrogenase active site. The bidentate nature of the P(R)2N(Ph)2 ligands
      was found to be crucial for the preferential formation of coordinatively
      unsaturated penta-coordinate complexes, which is supported by first principle
      calculations. IR-spectroscopic data suggest the presence of coordination isomers
      around the metal center, as well as multiple possible conformers of the
      P(R)2N(Ph)2 ligand. This finding is further corroborated by X-ray
      crystallographic and computational studies. (31)P{(1)H}-NMR- and IR-spectroscopic
      as well as electrochemical measurements show that the electronic properties of
      the complexes are strongly, and independently, influenced by the P-substituents
      at the P(R)2N(Ph)2 ligand as well as by modifications of the bdt bridge. These
      results illustrate the advantages of this modular platform, which allows
      independent and selective tuning through site specific modifications. Potential
      catalytic intermediates, namely singly reduced and protonated complexes, have
      been further investigated by spectroscopic methods and exhibit remarkable
      stability. Finally, their general capacity for electro-catalytic reduction of
      protons to molecular hydrogen was verified. 

PMID- 24457902
TI  - Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with
      osteolytic function.
AB  - Pentraxin 3 (PTX3), a modulator of tumor-associated inflammation, is known to be
      positively correlated with tumor grade and severity of malignancies, but its
      exact role remains unclear. This study found that PTX3 expression was up
      regulated in distant bone metastases of breast cancer compared to lung, liver,
      and brain metastases in 64 human breast cancer patients. Elevated expression of
      PTX3 was correlated with poor survival in patients with breast cancer. PTX3
      expression was also up-regulated in a bone metastatic breast cancer cell line and
      further enhanced by pro-inflammatory cytokine TNFalpha. Administration of PTX3
      promoted the migratory potential of breast cancer cells and the mobilization of
      macrophages, a precursor of osteoclasts (OCs), toward breast cancer cells. In
      addition, elevated expression of PTX3 by TNFalpha led to enhanced OC formation,
      implying the distinct role of PTX3 in osteolytic bone metastasis of breast cancer
      cells. Furthermore, PTX3 silencing using PTX3-specific siRNA prevented breast
      cancer cell migration, macrophage chemotaxis, and subsequent OC formation. These
      findings provide an important insight into the key role of PTX3 in inflammation
      associated osteolytic complications of breast cancer. 

PMID- 24457904
TI  - Enzyme-controllable F-NMR turn on through disassembly of peptide-based
      nanospheres for enzyme detection.
AB  - The enzyme tyrosinase could trigger the disassembly of peptide-based nanospheres,
      resulting in F-NMR signal turning on. 

PMID- 24457905
TI  - Angiographic outcomes contradict platelet data in the PLATO trial: confusion over
      official trial substudies.
AB  - Major indication-seeking phase 3 clinical trials usually include numerous
      subanalyses and substudies designed to facilitate the interpretation of results,
      often providing putative mechanisms that might explain clinical outcomes. Such
      subanalyses and/or substudies may focus on socioeconomic implications, cost
      effectiveness, biomarker applicability, subgroup analyses, etc. Novel
      antiplatelet agents may benefit from substudies aimed at elucidating the effects
      on platelets, while angiographic data are also essential for the adequate
      assessment of coronary flow. Ideally, the data yielded from substudies should
      correlate well with the main results of the trial. However, in the PLATO
      (PLATelet Inhibition and Clinical Outcomes) trial, official angiographic data
      (PLATO-A) contradict platelet (PLATO-P) substudy results. While the large (n =
      2,616) PLATO-A concluded that coronary flow and myocardial perfusion were almost
      identical after ticagrelor or clopidogrel, the small (n = 24) single-center PLATO
      P suggested that ticagrelor achieved a highly significantly greater antiplatelet
      effect compared to clopidogrel after loading in patients enrolled in the same
      trial and at similar time points. In contrast to PLATO-P, PLATO-A corresponds
      well with clinical outcomes including the early percutaneous coronary
      intervention 'ticagrelor death paradox' in PLATO-USA patients and the lack of an
      early ticagrelor benefit in the overall invasive PLATO cohort reported by the
      FDA. The discrepancy between PLATO-A and PLATO-P is obvious and lacks a
      reasonable explanation: platelet activity and coronary flow are generally
      inversely related, as consistently shown for other antiplatelet regimens, and
      should be particularly matched when assessed in the frame of the same trial.

PMID- 24457906
TI  - On the syntactic monoids associated with a class of synchronized codes.
AB  - A complete code C over an alphabet A is called synchronized if there exist x, y ?
      C* such that xA*?A*y?C*. In this paper we describe the syntactic monoid Syn(C
      (+)) of C (+) for a complete synchronized code C over A such that C (+), the
      semigroup generated by C, is a single class of its syntactic congruence P C (+) .
      In particular, we prove that, for such a code C, either C = A or Syn(C (+)) is
      isomorphic to a special submonoid of ?? (l) (I) * ?? (r) (Lambda), where ?? (l)
      (I) and ?? (r) (Lambda) are the full transformation semigroups on the nonempty
      sets I and Lambda, respectively. 

PMID- 24457907
TI  - Combinatorial regulation of lipoprotein lipase by microRNAs during mouse
      adipogenesis.
AB  - MicroRNAs (miRNAs) regulate gene expression directly through base pairing to
      their targets or indirectly through participating in multi-scale regulatory
      networks. Often miRNAs take part in feed-forward motifs where a miRNA and a
      transcription factor act on shared targets to achieve accurate regulation of
      processes such as cell differentiation. Here we show that the expression levels
      of miR-27a and miR-29a inversely correlate with the mRNA levels of lipoprotein
      lipase (Lpl), their predicted combinatorial target, and its key transcriptional
      regulator peroxisome proliferator-activated receptor gamma (Pparg) during 3T3-L1
      adipocyte differentiation. More importantly, we show that Lpl, a key lipogenic
      enzyme, can be negatively regulated by the two miRNA families in a combinatorial
      fashion on the mRNA and functional level in maturing adipocytes. This regulation
      is mediated through the Lpl 3'UTR as confirmed by reporter gene assays. In
      addition, a small mathematical model captures the dynamics of this feed-forward
      motif and predicts the changes in Lpl mRNA levels upon network perturbations. The
      obtained results might offer an explanation to the dysregulation of LPL in
      diabetic conditions and could be extended to quantitative modeling of regulation
      of other metabolic genes under similar regulatory network motifs. 

PMID- 24457908
TI  - Fiber type-specific expression of low-density lipoprotein receptor-related
      protein 6 in human skeletal muscles.
AB  - OBJECTIVE: Gene expression patterns differ in the two types of skeletal muscle
      fiber. The Wnt signaling pathway, which includes low-density lipoprotein receptor
      related protein 6 (LRP6), has been associated with cell differentiation and
      glucose metabolism in skeletal muscles. We examined the relationships between
      muscle fiber types and LRP6 expression. METHODS: Adenosine triphosphatase was
      assayed histochemically, and the levels of expression of LRP6 and myosin were
      analyzed immunohistochemically, in frozen sections of muscle fiber obtained from
      16 muscle biopsy samples. The expression pattern of LRP6 in C2C12 cells was
      assayed by immunocytochemistry. RESULTS: LRP6 was expressed only in type II
      fibers. Type IIc fibers showed variations in LRP6 expression. Expression of LRP6
      was observed at the stage of myoblast differentiation. CONCLUSION: Antibody to
      LRP6 may be useful for identifying type II skeletal muscle fibers. LRP6 may
      influence glucose metabolism in type II fibers of human skeletal muscles.

PMID- 24457909
TI  - Impact of transition metal on nitrogen retention and activity of iron-nitrogen
      carbon oxygen reduction catalysts.
AB  - Iron based nitrogen doped carbon (FeNC) catalysts are synthesized by high
      pressure pyrolysis of carbon and melamine with varying amounts of iron acetate in
      a closed, constant-volume reactor. The optimum nominal amount of Fe (1.2 wt%) in
      FeNC catalysts is established through oxygen reduction reaction (ORR)
      polarization. Since the quantity of iron used in FeNCs is very small, the amount
      of Fe retained in FeNC catalysts after leaching is determined by UV-VIS
      spectroscopy. As nitrogen is considered to be a component of active sites, the
      amount of bulk and surface nitrogen retention in FeNC catalysts are measured
      using elemental analysis and X-ray photoelectron spectroscopy, respectively. It
      is found that increasing nominal Fe content in FeNC catalysts leads to a
      decreased level of nitrogen retention. Thermogravimetric analysis demonstrates
      that increasing nominal Fe content leads to increased weight loss during
      pyrolysis, particularly at high temperatures. Catalysts are also prepared in the
      absence of iron source, and with iron removed by washing with hot aqua regia post
      pyrolysis. FeNC catalysts prepared with no Fe show high retained nitrogen content
      but poor ORR activity, and aqua regia washed catalysts demonstrate similar
      activity to Fe-free catalysts, indicating that Fe is an active site component. 

PMID- 24457910
TI  - Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells.
AB  - Arrestin domain-containing 3 (ARRDC3) is a tumor suppressor whose expression is
      either lost or suppressed in basal-like breast cancer (BLBC). However, the
      mechanism by which BLBC suppresses ARRDC3 expression is not established. Here, we
      show that expression of ARRDC3 in BLBC cells is suppressed at the transcriptional
      level. Suppression of ARRDC3 expression in BLBC cells involves epigenetic
      silencing as inhibitors of class III histone deacetylases (HDACs) significantly
      restores ARRDC3 levels in BLBC cells. SIRT2, among class III HDACs, plays a major
      role in epigenetic silencing of ARRDC3 in MDA-MB-231 cells. Acetylation levels of
      the ARRDC3 promoter in BLBC cells is significantly lower than that of other sub
      types of BC cells. Chromatin immunopreciptitation analysis established SIRT2
      binding at ARRDC3 promoter in BLBC cells. Our studies indicate that SIRT2
      dependent epigenetic silencing of ARRDC3 is one of the important events that may
      contribute to the aggressive nature of BLBC cells. 

PMID- 24457911
TI  - Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast
      cancer: results from the GEICAM/2006-14 trial.
AB  - BACKGROUND: The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant
      chemotherapy increases the pathological complete response (pCR) rate in patients
      with human epidermal growth factor receptor 2 (HER2)-positive early breast
      cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and
      specific efficacy biomarkers. METHODS: Patients with stages I-III (including
      inflammatory) HER2-positive breast cancer were randomised to receive epirubicin
      (E) plus cyclophosphamide (C) * 4 cycles followed by docetaxel (D) plus either T
      (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response,
      toxicity, and pCR-predictive biomarkers. RESULTS: We randomised 102 patients to
      EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had
      oestrogen receptor (ER)-positive tumours. Pathological complete response in
      breast was 52.1% (95% CI:38.0-66.2%) for EC-DT and 25.5% (95% CI:13.5-37.5%) for
      EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9%
      for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3-4 toxicity did not differ across
      treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030).
      Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the
      only predictors of pCR in both groups. CONCLUSION: EC-DT exhibited higher
      efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only
      the absence of ER expression was associated with increased pCR.

PMID- 24457913
TI  - Efficient engineering of a bacteriophage genome using the type I-E CRISPR-Cas
      system.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR
      associated (Cas) system has recently been used to engineer genomes of various
      organisms, but surprisingly, not those of bacteriophages (phages). Here we
      present a method to genetically engineer the Escherichia coli phage T7 using the
      type I-E CRISPR-Cas system. T7 phage genome is edited by homologous recombination
      with a DNA sequence flanked by sequences homologous to the desired location. Non
      edited genomes are targeted by the CRISPR-Cas system, thus enabling isolation of
      the desired recombinant phages. This method broadens CRISPR Cas-based editing to
      phages and uses a CRISPR-Cas type other than type II. The method may be adjusted
      to genetically engineer any bacteriophage genome. 

PMID- 24457912
TI  - FGFR2 amplification has prognostic significance in gastric cancer: results from a
      large international multicentre study.
AB  - BACKGROUND: In preclinical gastric cancer (GC) models, FGFR2 amplification was
      associated with increased tumour cell proliferation and survival, and drugs
      targeting this pathway are now in clinical trials. METHODS: FGFR2 FISH was
      performed on 961 GCs from the United Kingdom, China and Korea, and the
      relationship with clinicopathological data and overlap with HER2 amplification
      were analysed. RESULTS: The prevalence of FGFR2 amplification was similar between
      the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral
      heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification
      was associated with lymph node metastases (P<0.0001). FGFR2 amplification and
      polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83
      vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and
      FGFR2 amplification was an independent marker of poor survival in the UK cohort
      (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level
      amplifications did co-occur these were detected in distinct areas of the tumour.
      CONCLUSION: A similar incidence of FGFR2 amplification was found in Asian and UK
      GCs and was associated with lymphatic invasion and poor prognosis. This study
      also shows that HER2 and FGFR2 amplifications are mostly exclusive.

PMID- 24457914
TI  - Manual dexterity aptitude testing: a soap carving study.
AB  - IMPORTANCE: Currently there are few validated metrics for predicting surgical
      skill among otolaryngology residency applicants. OBJECTIVE: To determine whether
      manual dexterity aptitude testing in the form of soap carving during
      otolaryngology residency interviews at Kaiser Permanente Medical Center Oakland
      predicts surgical skill at the time of graduation from otolaryngology residency
      programs. DESIGN, SETTING, AND PARTICIPANTS: This study was conducted to
      determine how applicants with the best and worst soap carvings compared at the
      time of graduation with respect to various metrics including visuospatial ability
      and manual dexterity. Over the last 25 years, applicants to the residency program
      at Kaiser Permanente Oakland were required to carve soap during their residency
      interview. The 3 best and 3 worst soap carvings from 1990 through 2006 were
      determined. Of the individuals who carved those soaps, 62 qualified for the study
      and matriculated into otolaryngology residency programs. INTERVENTIONS: Surveys
      were sent to the 62 individuals' residency programs to evaluate those individuals
      on a 5-point Likert scale in various categories as well as to rank those
      individuals as being in the top 50% or bottom 50% of their graduating class. MAIN
      OUTCOMES AND MEASURES: All else being equal, we hypothesized that applicants who
      had the manual dexterity and visuospatial skills to accurately carve a bar of
      soap would more likely possess the skills necessary to become a good surgeon.
      RESULTS: There was no difference between individuals with the best soap carvings
      and those with the worst soap carvings in all categories: cognitive knowledge,
      visuospatial ability, manual dexterity, decision making, and overall score (P >
      .10 for all categories). There was a 95% response rate, with 35 of 37 residency
      programs responding and 59 of 62 surveys returned. CONCLUSIONS AND RELEVANCE:
      Manual dexterity aptitude testing in the form of soap carving does not appear to
      correlate with surgical skill at the time of graduation. Further studies need to
      be conducted to determine the role of manual dexterity and visuospatial aptitude
      testing in the otolaryngology application process.

PMID- 24457915
TI  - Positive FDG-PET/CT of the pleura twenty years after talc pleurodesis: three
      cases of benign talcoma.
AB  - The FDG-PET (fluorine-18 fluorodeoxyglucose positron emission tomography) scan is
      used with increasing frequency to investigate pleural abnormalities and to
      determine the possibility of neoplastic invasion. However, false-positive
      findings are not uncommon and talc pleurodesis has been reported to cause
      hypermetabolic pleural thickenings up to 5 years after the procedure. We report
      the cases of 3 patients (2 of whom had a history of asbestos exposure) requiring
      talc pleurodesis for recurrent pneumothoraces between 1988 and 1990, who were
      investigated in 2011 for pleural abnormalities. Avid pleural thickening on FDG
      PET scan mimicking pleural cancer was found, but this was deemed secondary to the
      pleurodesis. Talc pleurodesis generates inflammation which promotes pleural
      adhesions. This inflammatory reaction could decrease with time, as in other
      inflammatory processes. Since talc is not metabolized by the body, the FDG-PET
      scan can remain positive, most likely because of a foreign-body granulomatous
      reaction, even 20 years later. It is important to be aware of this possibility
      and to question patients with pleural abnormalities about past procedures and
      mention such procedures to the colleagues who are responsible for interpreting
      metabolic imaging. Follow-up of hypermetabolic pleural lesions attributed to talc
      pleurodesis is important for the detection of new pleural lesions or neoplastic
      evolution.

PMID- 24457916
TI  - Using eye movements to evaluate the cognitive processes involved in text
      comprehension.
AB  - The present article describes how to use eye tracking methodologies to study the
      cognitive processes involved in text comprehension. Measuring eye movements
      during reading is one of the most precise methods for measuring moment-by-moment
      (online) processing demands during text comprehension. Cognitive processing
      demands are reflected by several aspects of eye movement behavior, such as
      fixation duration, number of fixations, and number of regressions (returning to
      prior parts of a text). Important properties of eye tracking equipment that
      researchers need to consider are described, including how frequently the eye
      position is measured (sampling rate), accuracy of determining eye position, how
      much head movement is allowed, and ease of use. Also described are properties of
      stimuli that influence eye movements that need to be controlled in studies of
      text comprehension, such as the position, frequency, and length of target words.
      Procedural recommendations related to preparing the participant, setting up and
      calibrating the equipment, and running a study are given. Representative results
      are presented to illustrate how data can be evaluated. Although the methodology
      is described in terms of reading comprehension, much of the information presented
      can be applied to any study in which participants read verbal stimuli. 

PMID- 24457917
TI  - Physiology, behavior, and conservation.
AB  - Many animal populations are in decline as a result of human activity.
      Conservation practitioners are attempting to prevent further declines and loss of
      biodiversity as well as to facilitate recovery of endangered species, and they
      often rely on interdisciplinary approaches to generate conservation solutions.
      Two recent interfaces in conservation science involve animal behavior (i.e.,
      conservation behavior) and physiology (i.e., conservation physiology). To date,
      these interfaces have been considered separate entities, but from both pragmatic
      and biological perspectives, there is merit in better integrating behavior and
      physiology to address applied conservation problems and to inform resource
      management. Although there are some institutional, conceptual, methodological,
      and communication-oriented challenges to integrating behavior and physiology to
      inform conservation actions, most of these barriers can be overcome. Through
      outlining several successful examples that integrate these disciplines, we
      conclude that physiology and behavior can together generate meaningful data to
      support animal conservation and management actions. Tangentially, applied
      conservation and management problems can, in turn, also help advance and
      reinvigorate the fundamental disciplines of animal physiology and behavior by
      providing advanced natural experiments that challenge traditional frameworks.

PMID- 24457918
TI  - Intraspecific variation in thermal tolerance and acclimation capacity in brook
      trout (Salvelinus fontinalis): physiological implications for climate change.
AB  - Cold-water fishes are becoming increasingly vulnerable as changing thermal
      conditions threaten their future sustainability. Thermal stress and habitat loss
      from increasing water temperatures are expected to impact population viability,
      particularly for inland populations with limited adaptive resources. Although the
      long-term persistence of cold-adapted species will depend on their ability to
      cope with and adapt to changing thermal conditions, very little is known about
      the scope and variation of thermal tolerance within and among conspecific
      populations and evolutionary lineages. We studied the upper thermal tolerance and
      capacity for acclimation in three captive populations of brook trout (Salvelinus
      fontinalis) from different ancestral thermal environments. Populations differed
      in their upper thermal tolerance and capacity for acclimation, consistent with
      their ancestry: the northernmost strain (Lake Nipigon) had the lowest thermal
      tolerance, while the strain with the most southern ancestry (Hill's Lake) had the
      highest thermal tolerance. Standard metabolic rate increased following
      acclimation to warm temperatures, but the response to acclimation varied among
      strains, suggesting that climatic warming may have differential effects across
      populations. Swimming performance varied among strains and among acclimation
      temperatures, but strains responded in a similar way to temperature acclimation.
      To explore potential physiological mechanisms underlying intraspecific
      differences in thermal tolerance, we quantified inducible and constitutive heat
      shock proteins (HSP70 and HSC70, respectively). HSPs were associated with
      variation in thermal tolerance among strains and acclimation temperatures; HSP70
      in cardiac and white muscle tissues exhibited similar patterns, whereas
      expression in hepatic tissue varied among acclimation temperatures but not
      strains. Taken together, these results suggest that populations of brook trout
      will vary in their ability to cope with a changing climate.

PMID- 24457919
TI  - Are tropical small mammals physiologically vulnerable to Arrhenius effects and
      climate change?
AB  - There is some urgency in the necessity to incorporate physiological data into
      mechanistic, trait-based, demographic climate change models. Physiological
      responses at the individual level provide the mechanistic link between
      environmental changes and individual performances and hence population dynamics.
      Here we consider the causal relationship between ambient temperature (Ta) and
      metabolic rate (MR), namely, the Arrhenius effect, which is directly affected by
      global warming through increases in average global air temperatures and the
      increase in the frequency and intensity of extreme climate events. We measured
      and collated data for several small, free-ranging tropical arboreal mammals and
      evaluated their vulnerability to Arrhenius effects and putative heat stress
      associated with climate change. Skin temperatures (Tskin) were obtained from free
      ranging tarsiers (Tarsius syrichta) on Bohol Island, Philippines. Core body
      temperature (Tb) was obtained from the greater hedgehog tenrec (Setifer setosus)
      and the gray brown mouse lemur (Microcebus ravelobensis) from Ankarafantsika,
      Madagascar. Tskin for another mouse lemur, Microcebus griseorufus, was obtained
      from the literature. All four species showed evidence of hyperthermia during the
      daytime rest phase in the form of either Tskin or Tb that was higher than the
      normothermic Tb during the nighttime active phase. Potentially, tropical arboreal
      mammals with the lowest MRs and Tb, such as tarsiers, are the most vulnerable to
      sustained heat stress because their Tb is already close to Ta. Climate change may
      involve increases in MRs due to Arrhenius effects, especially during the rest
      phase or during torpor and hibernation. The most likely outcome of increased
      Arrhenius effects with climate change will be an increase in energy expenditure
      at the expense of other critical functions such as reproduction or growth and
      will thus affect fitness. However, we propose that these hypothetical Arrhenius
      costs can be, and in some species probably are, offset by the use of hyperthermic
      daily torpor, that is, hypometabolism at high Ta.

PMID- 24457920
TI  - Dehydration and drinking behavior of the marine file snake Acrochordus
      granulatus.
AB  - Dehydration and drinking behaviors were investigated in the little file snake
      (Acrochordus granulatus) collected from marine populations in the Philippines and
      in Australia. File snakes dehydrate in seawater and do not drink seawater when
      dehydrated in air and offered seawater to drink. Dehydrated file snakes drink
      freshwater, and the threshold of dehydration for first drinking response is a
      deficit of -7.4% +/- 2.73% (mean +/- SD) of original body mass. The thirst
      mechanism in this species is more sensitive than that recently studied in sea
      snakes. The volume of water ingested increases with increasing dehydration. Mean
      plasma osmolality was 278.89 +/- 33.17 mMol/kg, mean hematocrit was 59% +/-
      5.45%, and both decreased in snakes that drank freshwater following acclimation
      in seawater. Snakes always drank freshwater at the water's surface, testing water
      with tongue flicks between each swallowing of water. Some snakes ingested large
      volumes of freshwater, approaching 50% of body mass. Visual observations and
      measurements of osmolality in plasma and stomach fluids suggest that water is
      taken up from the gut and dilutes body fluids slowly over the course of 48 h or
      longer. Eighty percent of snakes that were collected during the dry season
      (following >4 mo of drought) in Australia drank freshwater immediately following
      their capture, indicating that snakes were dehydrated in their marine environment
      even when known to have been feeding at the time. Snakes kept in seawater
      maintained a higher state of body condition when freshwater was periodically
      available. These results support a growing conclusion that diverse taxa of marine
      snakes require environmental sources of freshwater to maintain water balance,
      contrary to earlier belief. Identifying the freshwater requirements of
      secondarily marine vertebrates is important for better understanding how they
      maintain water balance in marine habitats, especially with respect to
      conservation in changing environments.

PMID- 24457921
TI  - Winter energetics of female Indiana bats Myotis sodalis.
AB  - Understanding physiological limits and environmental optima is critical to
      developing protection strategies for endangered and threatened species. One
      theory to explain the decline in endangered Indiana bat Myotis sodalis
      populations involves increasing cave temperatures in winter hibernacula. Altered
      cave temperatures can raise metabolism and cause more arousals in torpid bats,
      both of which use more fat reserves. In addition, fluctuations in cave
      temperatures may cause additional arousals. Our objectives were to quantify the
      effect of temperature and fluctuations thereof on torpid metabolism and arousal
      frequency in this species. Female Indiana bats (n=36) were collected from caves
      just before hibernation, maintained in an environmental chamber that simulated
      hibernacula conditions, and had skin temperature recorded every 30 min throughout
      the winter. One environmental chamber containing bats (n=12) was sequentially set
      at 8 degrees , 6 degrees , and 4 degrees C over the winter. The second chamber
      containing bats (n=12) experienced the same mean temperatures, but temperature
      fluctuated +/-2 degrees C on a regular basis. Torpor bouts were longest at 4
      degrees C and were not affected by temperature fluctuations. However, the
      temperature fluctuations appeared to cause longer arousals. Other bats (n=12)
      were individually placed in metabolic chambers to calculate oxygen consumption
      during torpor and during arousals. Torpid metabolism was affected by temperature;
      at 9 degrees C, it was higher than at 7 degrees  or 5 degrees C. Metabolism
      during arousals was not different among temperature treatments, but rates were
      almost 200 times higher than torpid metabolic rates. We calculated a winter
      energy budget and, from the energetic perspective, determined an optimum
      hibernation temperature (3 degrees -6 degrees C) for female Indiana bats. These
      findings suggest that hibernacula that provide these conditions deserve extra
      protection, although other factors in addition to energetics may play a role in
      temperature preferences.

PMID- 24457922
TI  - Does feeding behavior facilitate trophic niche partitioning in two sympatric
      sucker species from the American Southwest?
AB  - We examined two sympatric desert fishes, Sonora suckers (Catostomus insignis) and
      desert suckers (Pantosteus clarkii), and asked, does feeding behavior facilitate
      trophic niche partitioning? To answer this question, we conducted laboratory
      based feeding trials to determine whether morphology alone facilitates the diet
      separation between the relatively unspecialized, omnivorous Sonora sucker and the
      more morphologically specialized, algivorous desert sucker or whether behavioral
      differences accompany morphological specialization. We predicted that (1)
      algivorous desert suckers would maximize contact between jaws and substrate and
      produce a large mouth-gape to facilitate scraping attached food-material; (2)
      omnivorous Sonora suckers would be more effective suction feeders when consuming
      unattached food items from the benthos; and (3) because they are anatomically
      specialized for scraping, desert suckers could not alter their feeding behavior
      when presented with different prey types, whereas relatively unspecialized Sonora
      suckers could vary behavior with prey type. We found that both species maximized
      jaw contact when feeding on benthic-attached food, although desert suckers
      produced a greater gape area. We also found that Sonora suckers were more
      effective suction feeders when feeding on benthic-unattached prey. Counter to our
      initial predictions, both species altered key aspects of feeding behavior in
      response to different prey types/locations. It appears that both sucker species
      can function as generalist feeders to exploit a variety of prey types within
      their natural habitat; indeed, this behavioral versatility may allow desert and
      Sonora suckers to respond to the cyclic environmental changes that are
      characteristic of the aquatic habitats of the American Southwest.

PMID- 24457923
TI  - Digestive efficiencies of ex situ and in situ West Indian manatees (Trichechus
      manatus latirostris).
AB  - Digestive efficiencies (Dm) of ex situ and in situ manatees (Trichechus manatus
      latirostris) were, for the first time, assessed using manganese (Mn(2+)) as a
      naturally occurring marker. The Dm of ex situ manatees determined using [Mn(2+)]
      did not differ significantly from the Dm assessed using lignin, supporting the
      efficacy of the manganese approach. Gastrointestinal tract samples, obtained from
      recently dead animals, showed [Mn(2+)] concentrations were lowest in the stomach
      and remained low in the duodenum and small intestine but increased in the cecum,
      colon, and rectum, consistent with colonic digestion and absorption. In situ
      manatees consuming marine vegetation had significantly lower Dm (mean +/- SE,
      46.9% +/- 1.8%; n=8) than did in situ manatees consuming freshwater vegetation
      (77.8% +/- 2.6%; n=7), which in turn had significantly lower values than did ex
      situ manatees consuming lettuce (84.0% +/- 0.7%; n=37). In situ manatees eating
      seagrasses had significantly higher Dm than did long-term ex situ animals
      consuming seagrass for short periods of time (46.9% +/- 1.8% vs. 36.2% +/- 1.2%,
      respectively), suggesting potential modification of gut flora over time. One
      significant ramification of our results is that manatees consuming seagrasses
      would require a greater standing biomass to support their needs than would be
      required if they were eating freshwater vegetation. This reinforces the critical
      need to implement habitat conservation and protection before considering
      downlisting or delisting manatees as an endangered species.

PMID- 24457924
TI  - Physiological variation among invasive populations of the brown anole (Anolis
      sagrei).
AB  - Invasive species often encounter novel climatic conditions when they spread
      outside of their native ranges. Invading populations can respond to novel
      conditions by acclimation or adaptation of physiological capacities, which may
      facilitate their spread. We investigated differences in physiological traits
      among three populations of an invasive lizard, the brown anole (Anolis sagrei),
      along the latitudinal extent of its invasion in the southeastern United States.
      We predicted latitudinal clines for most traits based on models of adaptation to
      climate. Consistent with the latitudinal cline in temperature and moisture, the
      mean critical thermal minimum and the mean rate of water loss were lowest for
      lizards in the northern population. Furthermore, these traits acclimated to
      either temperature or humidity in a direction consistent with adaptive phenotypic
      plasticity. By contrast, metabolic rates varied among populations but did not
      conform to our prediction based on a latitudinal cline in temperature. Critical
      thermal maxima, endurances, and sprint speeds were similar among populations.
      Despite the idea that tropical lizards have limited capacity for acclimation, we
      found variation among invasive populations of brown anoles, which could have
      partially resulted from acclimation. This physiological variation within the
      invasive range raises questions about the roles of plasticity and adaptation in
      the success of the invasion.

PMID- 24457925
TI  - Physiological vagility: correlations with dispersal and population genetic
      structure of amphibians.
AB  - Physiological vagility represents the capacity to move sustainably and is central
      to fully explaining the processes involved in creating fine-scale genetic
      structure of amphibian populations, because movement (vagility) and the duration
      of movement determine the dispersal distance individuals can move to interbreed.
      The tendency for amphibians to maintain genetic differentiation over relatively
      short distances (isolation by distance) has been attributed to their limited
      dispersal capacity (low vagility) compared with other vertebrates. Earlier
      studies analyzing genetic isolation and population differentiation with distance
      treat all amphibians as equally vagile and attempt to explain genetic
      differentiation only in terms of physical environmental characteristics. We
      introduce a new quantitative metric for vagility that incorporates aerobic
      capacity, body size, body temperature, and the cost of transport and is
      independent of the physical characteristics of the environment. We test our
      metric for vagility with data for dispersal distance and body mass in amphibians
      and correlate vagility with data for genetic differentiation (F'(ST)). Both
      dispersal distance and vagility increase with body size. Differentiation (F'(ST))
      of neutral microsatellite markers with distance was inversely and significantly
      (R2=0.61) related to ln vagility. Genetic differentiation with distance was not
      significantly related to body mass alone. Generalized observations are validated
      with several specific amphibian studies. These results suggest that interspecific
      differences in physiological capacity for movement (vagility) can contribute to
      genetic differentiation and metapopulation structure in amphibians.

PMID- 24457926
TI  - Reach-scale land use drives the stress responses of a resident stream fish.
AB  - Abstract To date, relatively few studies have tried to determine the practicality
      of using physiological information to help answer complex ecological questions
      and assist in conservation actions aimed at improving conditions for fish
      populations. In this study, the physiological stress responses of fish were
      evaluated in-stream between agricultural and forested stream reaches to determine
      whether differences in these responses can be used as tools to evaluate
      conservation actions. Creek chub Semotilus atromaculatus sampled directly from
      forested and agricultural stream segments did not show differences in a suite of
      physiological indicators. When given a thermal challenge in the laboratory, creek
      chub sampled from cooler forested stream reaches had higher cortisol levels and
      higher metabolic stress responses to thermal challenge than creek chub collected
      from warmer and more thermally variable agricultural reaches within the same
      stream. Despite fish from agricultural and forested stream segments having
      different primary and secondary stress responses, fish were able to maintain
      homeostasis of other physiological indicators to thermal challenge. These results
      demonstrate that local habitat conditions within discrete stream reaches may
      impact the stress responses of resident fish and provide insight into changes in
      community structure and the ability of tolerant fish species to persist in
      agricultural areas. 

PMID- 24457927
TI  - Disentangling the roles of air exposure, gill net injury, and facilitated
      recovery on the postcapture and release mortality and behavior of adult migratory
      sockeye salmon (Oncorhynchus nerka) in freshwater.
AB  - We sought to improve the understanding of delayed mortality in migrating sockeye
      salmon (Oncorhynchus nerka) captured and released in freshwater fisheries. Using
      biotelemetry, blood physiology, and reflex assessments, we evaluated the relative
      roles of gill net injury and air exposure and investigated whether using a
      recovery box improved survival. Fish (n=238), captured by beach seine, were
      allocated to four treatment groups: captured only, air exposed, injured, and
      injured and air exposed. Only half of the fish in each group were provided with a
      15-min facilitated recovery. After treatment, fish were radio-tagged and released
      to resume their migration. Blood status was assessed in 36 additional untagged
      fish sampled after the four treatments. Compared with fish sampled immediately on
      capture, all treatments resulted in elevated plasma lactate and cortisol
      concentrations. After air exposure, plasma osmolality was elevated and reflexes
      were significantly impaired relative to the control and injured treatments.
      Injured fish exhibited reduced short-term migration speed by 3.2 km/d and had a
      14.5% reduced survival to subnatal watersheds compared to controls. The 15-min
      facilitated recovery improved reflex assessment relative to fish released
      immediately but did not affect survival. We suggest that in sockeye salmon
      migrating in cool water temperatures (~13 degrees -16 degrees C), delayed
      mortality can result from injury and air exposure, perhaps through sublethal
      stress, and that injury created additive delayed mortality likely via secondary
      infections.

PMID- 24457928
TI  - Refuge-seeking impairments mirror metabolic recovery following fisheries-related
      stressors in the Spanish flag snapper (Lutjanus carponotatus) on the Great
      Barrier Reef.
AB  - Fisheries and marine park management strategies for large predatory reef fish can
      mean that a large proportion of captured fish are released. Despite being
      released, these fish may experience high mortality while they traverse the water
      column to locate suitable refuge to avoid predators, all the while recovering
      from the stress of capture. The predatory reef fish Spanish flag snapper
      (Lutjanus carponotatus) is frequently released because of a minimum-size or bag
      limit or by fishers targeting more desirable species. Using L. carponotatus as a
      model, we tested whether simulated fishing stress (exercise and air exposure)
      resulted in impairments in reflexes (e.g., response to stimuli) and the ability
      to identify and use refuge in a laboratory arena and whether any impairments were
      associated with blood physiology or metabolic recovery. Control fish were
      consistently responsive to reflex tests and rapidly located and entered refugia
      in the arena within seconds. Conversely, treatment fish (exhausted and air
      exposed) were unresponsive to stimuli, took longer to search for refugia, and
      were more apprehensive to enter the refuge once it was located. Consequently,
      treatment fish took more than 70 times longer than control fish to enter the
      coral refuge (26.12 vs. 0.36 min, respectively). The finding that fish exposed to
      stress were hesitant to use refugia suggests that there was likely cognitive,
      visual, and/or physiological impairment. Blood lactate, glucose, and hematocrit
      measures were perturbed at 15 and 30 min after the stressor, relative to
      controls. However, measurements of oxygen consumption rate revealed that about
      50% of metabolic recovery occurred within 30 min after the stressor, coinciding
      with apparent cognitive/visual/physiological recovery. Recovering the treatment
      fish in aerated, flow-through chambers for 30 min before introduction to the
      behavioral arena restored reflexes, and "recovered" fish behaved more similarly
      to controls. Therefore, we suggest that temporarily holding coral reef fish that
      have undergone an exhaustive fishing interaction and an air exposure episode
      should enable significant recovery of cognitive and metabolic attributes that
      would enable fish to more rapidly locate and utilize refugia to avoid postrelease
      predation. However, after nonexhaustive fishing interactions (i.e., minimal
      reflex impairment), it is likely that immediate release would be most beneficial.

PMID- 24457929
TI  - Comparative physiology and relative swimming performance of three redhorse
      (Moxostoma spp.) species: associations with fishway passage success.
AB  - Our understanding of biological criteria to inform fish passage design is
      limited, partially due to the lack of understanding of biological motivators,
      cues, and constraints, as well as a lack of biological performance evaluations of
      structures once they are built. The Vianney-Legendre vertical slot fishway on the
      Richelieu River, Quebec, Canada, passes large numbers of migrating redhorse
      (Moxostoma spp.) upriver to spawning grounds each year. We evaluated the
      physiological capacity and relative swimming ability of three redhorse species
      (Moxostoma anisurum, Moxostoma carinatum, Moxostoma macrolepidotum; silver,
      river, and shorthead redhorse, respectively) to determine how these biotic
      factors relate to variation in fishway passage success and duration. Shorthead
      redhorse had higher maximum metabolic rates and were faster swimmers than silver
      and river redhorse at their species-specific peak migration temperatures. Blood
      lactate and glucose concentrations recovered more quickly for river redhorse than
      for silver and shorthead redhorse, and river redhorse placed second in terms of
      metabolic recovery and swim speed. Interestingly, fish sampled from the top of
      the fishway had nearly identical lactate, glucose, and pH values compared to
      control fish. Using passive integrated transponders in 2010 and 2012, we observed
      that passage success and duration were highly variable among redhorse species and
      were not consistent among years, suggesting that other factors such as water
      temperature and river flows may modulate passage success. Clearly, additional
      research is needed to understand how organismal performance, environmental
      conditions, and other factors (including abundance of conspecifics and other
      comigrants) interact with fishway features to dictate which fish will be
      successful and to inform research of future fishways. Our research suggests that
      there may be an opportunity for a rapid assessment approach where fish chased to
      exhaustion to determine maximal values of physiological disturbance are compared
      to fish sampled from the top of the fishway, which could reveal which species (or
      sizes of fish) are approaching or exceeding their physiological capacity during
      passage.

PMID- 24457930
TI  - Effects of body condition on buoyancy in endangered North Atlantic right whales.
AB  - Buoyancy is an important consideration for diving marine animals, resulting in
      specific ecologically relevant adaptations. Marine mammals use blubber as an
      energy reserve, but because this tissue is also positively buoyant, nutritional
      demands have the potential to cause considerable variation in buoyancy. North
      Atlantic right whales Eubalaena glacialis are known to be positively buoyant as a
      result of their blubber, and the thickness of this layer varies considerably, but
      the effect of this variation on buoyancy has not been explored. This study
      compared the duration and rate of ascending and descending glides, recorded with
      an archival tag, with blubber thickness, measured with an ultrasound device, in
      free-swimming right whales. Ascending whales with thicker blubber had shorter
      portions of active propulsion and longer passive glides than whales with thinner
      blubber, suggesting that blubber thickness influences buoyancy because the
      buoyant force is acting in the same direction as the animal's movement during
      this phase. Whales with thinner layers also used similar body angles and
      velocities when traveling to and from depth, while those with thicker layers used
      shallower ascent angles but achieved higher ascent velocities. Such alterations
      in body angle may help to reduce the cost of transport when swimming against the
      force of buoyancy in a state of augmented positive buoyancy, which represents a
      dynamic response to reduce the energetic consequences of physiological changes.
      These results have considerable implications for any diving marine animal during
      periods of nutritional stress, such as during seasonal migrations and annual
      variations in prey availability.

PMID- 24457931
TI  - Island life shapes the physiology and life history of eastern bluebirds (Sialia
      sialis).
AB  - Abstract Island organisms face a range of extrinsic threats to their
      characteristically small populations. Certain biological differences between
      island and continental organisms have the potential to exacerbate these threats.
      Understanding how island birds differ from their continental relatives may
      provide insight into population viability and serve as a predictive tool for
      conservation efforts. We compared an eastern bluebird population in Ohio with a
      threatened population in Bermuda in terms of the birds' development, morphology,
      immunology, and reproduction. These comparisons revealed that island nestlings
      had shorter wings and island adults had longer wings than their continental
      analogs. Island nestlings also had shorter tarsi than continental nestlings at
      day 8 posthatch, but this difference was absent at day 15 and in adults. Adults
      weighed less in Bermuda than in Ohio, and both nestlings and adults in Bermuda
      exhibited higher levels of two immunological indexes (concentrations of an acute
      phase protein and titers of nonspecific antibodies). Clutch sizes and hatch rates
      did not differ between the island and continental populations; however, as the
      breeding season progressed, brood sizes declined in Bermuda, whereas no such
      decline occurred in Ohio. Despite these differences and differences in nestling
      development, island and continental parents fed their nestlings at equal rates.
      Overall, our results suggest that the Bermuda phenotype may be adjusted to
      certain aspects of the island environment but not to others. Efforts to conserve
      the bluebirds of Bermuda may be improved by focusing on the intraseasonal
      patterns in nestling mortality and, more generally, the survival probabilities of
      different age classes. 

PMID- 24457932
TI  - Physiological evidence that anthropogenic woodlots can substitute for native
      riparian woodlands as stopover habitat for migrant birds.
AB  - The ability to find sufficient high-quality stopover habitat is a crucial factor
      for successful migration for woodland migrant birds. Woodland habitats are scarce
      in the Northern Prairie region of North America, and natural woodlands have been
      greatly reduced concurrent with the appearance of small anthropogenic woodlands
      on the landscape. Landbird migrants use both natural and anthropogenic woodlands
      in this region as stopover habitats, but the relative quality of these two
      habitats is unknown. We assessed the relative habitat quality of the two habitats
      by comparing body mass (Mb) and plasma metabolites associated with fattening
      (triglycerides [TRIG]) or fat catabolism (beta-hydroxybutyrate [BUTY], glycerol
      [GLYC]) in individual species, taxa, and foraging guilds of migrating woodland
      birds during both spring and fall migrations. The only significant difference in
      Mb between birds in the two habitats occurred for fall yellow-rumped warblers
      (Setophaga coronata), where Mb was 8% greater in corridors than in woodlots. No
      significant between-habitat differences occurred for plasma TRIG at either
      season. Significant between-habitat differences for plasma BUTY occurred only for
      ruby-crowned kinglets (Regulus calendula; 61% higher in corridors) in fall.
      Plasma GLYC differed significantly between habitats for a few groups, including
      vireos (190% higher in woodlots), warbling vireos (Vireo gilvus; 263% higher in
      woodlots), and Nashville warblers (Oreothlypis ruficapilla; 226% higher in
      woodlots) in fall. The few significant differences and absence of a consistent
      direction of variation in Mb and plasma metabolites suggests similar stopover
      habitat quality in these two habitat types. Thus, during migration through the
      Northern Prairie region anthropogenic woodlots can, at least partially,
      substitute as stopover habitat for lost and degraded native riparian habitats for
      woodland birds.

PMID- 24457933
TI  - Temperature-dependent IR spectroscopic and structural study of 18-crown-6
      chelating ligand in the complexation with sodium surfactant salts and potassium
      picrate.
AB  - 18-crown-6 ether (18C6) complexes with the following anionic surfactants: sodium
      n-dodecylsulfate (18C6-NaDS), sodium 4-(1-pentylheptyl)benzenesulfonate (18C6
      NaDBS); and potassium picrate (18C6-KP) were synthesized and studied in terms of
      their thermal and structural properties. Physico-chemical properties of new solid
      1:1 coordination complexes were characterized by infrared (IR) spectroscopy,
      thermogravimetry and differential thermal analysis, differential scanning
      calorimetry, X-ray diffraction and microscopic observations. The strength of
      coordination between Na(+) and oxygen atoms of 18C6 ligand does not depend on
      anionic part of the surfactant, as established by thermodynamical parameters
      obtained by temperature-dependent IR spectroscopy. Each of these complexes
      exhibit different kinds of endothermic transitions in heating scan. Diffraction
      maxima obtained by SAXS and WAXS, refer the behavior of the compounds 18C6-NaDS
      and 18C6-NaDBS as smectic liquid crystalline. Distortion of 18C6-NaDS and 18C6-KP
      complexes occurs in two steps. Temperature of the decomplexation of solid crystal
      complex 18C6-KP is considerably higher than of mesophase complexes, 18C6-NaDS,
      and 18C6-NaDBS. The structural and liquid crystalline properties of novel 18
      crown-ether complexes are function of anionic molecule geometry, type of chosen
      cation (Na(+), K(+)), as well as architecture of self-organized aggregates. A
      good combination of crown ether unit and amphiphile may provide a possibility for
      preparing new functionalized materials, opening the research field of ion
      complexation and of host-guest type behavior. 

PMID- 24457934
TI  - Dinuclear nickel(II) triple-stranded supramolecular cylinders: syntheses,
      characterization and G-quadruplexes binding properties.
AB  - Three dinuclear nickel triple-stranded supramolecular cylinders [Ni2(L1)3][ClO4]4
      (1), [Ni2(L2)3][ClO4]4 (2) and [Ni2(L3)3][ClO4]4 (3) with bis(pyridylimine)
      Schiff base containing triphenyl groups in the spacers as ligands were
      synthesized and characterized. The human telomeric G-quadruplexes binding
      properties of cylinders 1-3 were evaluated by means of UV-Vis spectroscopy,
      circular dichroism (CD) spectroscopy and fluorescence resonance energy transfer
      (FRET) melting assay. UV-Vis studies revealed that the supramolecular cylinders 1
      3 could bind to G-quadruplex DNA with high binding constants (Kb values ranging
      from 0.11-2.2*10(6) M(-1)). FRET melting studies indicated that the cylinders 1-3
      had much stronger stabilizing effect on G-quadruplex DNA (DeltaTm up to 24.5
      degrees C) than the traditional cylinder Ni2L3(4+) just containing
      diphenylmethane spacers (DeltaTm=10.6  degrees C). Meanwhile, cylinders 1-3 were
      found to have a modest degree of selectivity for the quadruplex DNA versus duplex
      DNA in competition FRET assays. Moreover, CD spectroscopy revealed that complex 1
      could induce G-quadruplex formation in the absence of metal ions solution and
      convert antiparallel G-quadruplex into hybrid structure in Na(+) solution. These
      results provided a new insight into the development of supramolecular cylinders
      as potential anticancer drugs targeting G-quadruplex DNA.

PMID- 24457935
TI  - Spectral studies of 2-pyrazoline derivatives: structural elucidation through
      single crystal XRD and DFT calculations.
AB  - A series of biologically active N-thiocarbamoyl pyrazoline derivatives have been
      synthesized using anhydrous potassium carbonate as the catalyst. All the
      synthesized compounds were characterized by FT-IR, (1)H NMR, (13)C NMR spectral
      studies, LCMS, CHN Analysis and X-ray diffraction analysis (compound 7). In order
      to supplement the XRD parameters, molecular modelling was carried out by Gaussian
      03W. From the optimized structure, the energy, dipolemoment and HOMO-LUMO
      energies of all the systems were calculated. 

PMID- 24457937
TI  - Time-resolved magnetic sensing with electronic spins in diamond.
AB  - Quantum probes can measure time-varying fields with high sensitivity and spatial
      resolution, enabling the study of biological, material and physical phenomena at
      the nanometre scale. In particular, nitrogen-vacancy centres in diamond have
      recently emerged as promising sensors of magnetic and electric fields. Although
      coherent control techniques have measured the amplitude of constant or
      oscillating fields, these techniques are not suitable for measuring time-varying
      fields with unknown dynamics. Here we introduce a coherent acquisition method to
      accurately reconstruct the temporal profile of time-varying fields using Walsh
      sequences. These decoupling sequences act as digital filters that efficiently
      extract spectral coefficients while suppressing decoherence, thus providing
      improved sensitivity over existing strategies. We experimentally reconstruct the
      magnetic field radiated by a physical model of a neuron using a single electronic
      spin in diamond and discuss practical applications. These results will be useful
      to implement time-resolved magnetic sensing with quantum probes at the nanometre
      scale. 

PMID- 24457936
TI  - A vibrational spectroscopic study of the phosphate mineral minyulite
      KAl2(OH,F)(PO4)2?4(H2O) and in comparison with wardite.
AB  - Vibrational spectroscopy enables subtle details of the molecular structure of
      minyulite KAl2(OH,F)(PO4)2?4(H2O). Single crystals of a pure phase from a
      Brazilian pegmatite were used. Minyulite belongs to the orthorhombic crystal
      system. This indicates that it has three axes of unequal length, yet all are
      perpendicular to each other. The infrared and Raman spectroscopy were applied to
      compare the structure of minyulite with wardite. The reason for the comparison is
      that both are Al containing phosphate minerals. The Raman spectrum of minyulite
      shows an intense band at 1012 cm(-1) assigned to the nu1PO4(3-) symmetric
      stretching vibrations. A series of low intensity Raman bands at 1047, 1077, 1091
      and 1105 cm(-1) are assigned to the nu3PO4(3-) antisymmetric stretching modes.
      The Raman bands at 1136, 1155, 1176 and 1190 cm(-1) are assigned to AlOH
      deformation modes. The infrared band at 1014 cm(-1) is ascribed to the PO4(3-)
      nu1 symmetric stretching vibrational mode. The infrared bands at 1049, 1071, 1091
      and 1123 cm(-1) are attributed to the PO4(3-) nu3 antisymmetric stretching
      vibrations. The infrared bands at 1123, 1146 and 1157 cm(-1) are attributed to
      AlOH deformation modes. Raman bands at 575, 592, 606 and 628 cm(-1) are assigned
      to the nu4 out of plane bending modes of the PO4(3-) unit. In the 2600-3800 cm(
      1) spectral range, Raman bands for minyulite are found at 3661, 3669 and 3692 cm(
      1) are assigned to AlOH/AlF stretching vibrations. Broad infrared bands are also
      found at 2904, 3105, 3307, 3453 and 3523 cm(-1). Raman bands at 3225, 3324 cm(-1)
      are assigned to water stretching vibrations. A comparison is made with the
      vibrational spectra of wardite. Raman spectroscopy complimented with infrared
      spectroscopy has enabled aspects of the structure of minyulite to be ascertained
      and compared with that of other phosphate minerals.

PMID- 24457938
TI  - A minimally invasive technique for occluding large muscular ventricular septal
      defects in infants.
AB  - OBJECTIVE: This study investigated the feasibility, timing and indications for
      closure of large muscular ventricular septal defects (VSDs) in infants without
      use of a cardiopulmonary bypass. METHODS: A total of 9 infants with large
      muscular VSDs ranging in size from 7 to 15 mm were treated by minimally invasive
      closure without cardiopulmonary bypass between April 2010 and February 2013.
      RESULTS: All surgeries were successful without resulting in uncontrolled systemic
      infection, a pulmonary hypertensive crisis or a severely low cardiac output, and
      with an apparently shorter operation time and postoperative tracheal cannula.
      CONCLUSIONS: VSD closure without cardiopulmonary bypass can improve the efficacy
      and prognosis of infants with large muscular VSDs and concurrent pulmonary
      infections or respiratory failure.

PMID- 24457939
TI  - Neutral copper(I) dipyrrin complexes and their use as sensitizers in dye
      sensitized solar cells.
AB  - Heteroleptic neutral copper(I) dipyrrin complexes have been synthesised with the
      general formula [Cu(4,4'-(R)-6,6'-(CH3)-bipyridine)(dipyrrin)], R = CH3 or CO2Et,
      and H-dipyrrin is either 1,3,7,9-tetramethyldipyrromethene (HL1), 1,13-diphenyl
      6,8-diisoindolemethene (HL2), or 1,13-diphenyl-3,11-di(trifluoromethyl)-6,8
      diisoindolemethene (HL3). Improved stability was observed across the series ,
      likely due to better steric constraints between the ligands. Visible light
      absorption has also been enhanced with a red-shift in absorption from 450 nm to
      600 nm. Complex 3 shows photoluminescence lifetime in the order of nanoseconds
      suggesting singlet fluorescence which is supported by theoretical calculations.
      Study of the complexes as sensitisers in dye-sensitised solar cells was achieved
      by assembling the dye in situ on the surface of TiO2 in a series of steps
      (anchoring ligand followed by ancillary ligand and [Cu(CH3CN)4][BF4]. The highest
      efficiency achieved was 0.41% for the dye with HL3, attributed to better dye
      regeneration due to a more favourable oxidation potential.

PMID- 24457940
TI  - Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like
      receptors.
AB  - The RIG-I-like receptors (RLRs)--RIG-I, MDA5, and LGP2--detect intracellular
      pathogenic RNA and elicit an antiviral immune response during viral infection.
      The protein architecture of the RLR family consists of multiple functional
      domains, including N-terminal Caspase Activation and Recruitment Domains (CARDs)
      for signaling initiation, a central RNA helicase core, and a C-terminal domain
      for RNA sensing. With these specialized sensing-and-responding modules, RLRs are
      able to selectively bind non-self RNA species and trigger downstream signaling
      events leading to interferon production. This article summarizes the recent
      progress toward defining the precise mechanisms of RNA recognition and subsequent
      signal induction by RLRs.

PMID- 24457942
TI  - Novel bimetallic core-shell nanocrystal-clay composites with superior catalytic
      activities.
AB  - Clay (synthetic hectorite; Laponite XLG) plays a very crucial role in the
      formation and stabilization of core-shell nanocrystals and affords high
      stability, large BET surface area and stimulates the exceptional catalytic
      activity of the core-shell NCs. 

PMID- 24457941
TI  - Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor
      suppressive effects in breast cancer cells.
AB  - Balance between pro-tumor and anti-tumor effects may be affected by molecular
      interactions within tumor microenvironment. On this basis we searched for
      molecular partners of ADAMTS-12, a secreted metalloprotease that shows both
      oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a
      yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12
      interacting protein. Fibulins are components of basement membranes and elastic
      matrix fibers in connective tissue. Besides this structural function, fibulins
      also play crucial roles in different biological events, including tumorigenesis.
      To examine the functional consequences of the ADAMTS-12/fibulin-2 interaction, we
      performed different in vitro assays using two breast cancer cell lines: the
      poorly invasive MCF-7 and the highly invasive MDA-MB-231. Overall our data
      indicate that this interaction promotes anti-tumor effects in breast cancer
      cells. To assess the in vivo relevance of this interaction, we induced tumors in
      nude mice using MCF-7 cells expressing both ADAMTS-12 and fibulin-2 that showed a
      remarkable growth deficiency. Additionally, we also found that ADAMTS-12 may
      elicit pro-tumor effects in the absence of fibulin-2. Immunohistochemical
      staining of breast cancer samples allowed the detection of both ADAMTS-12 and
      fibulin-2 in the connective tissue surrounding tumor area in less aggressive
      carcinomas. However, both proteins are hardly detected in more aggressive tumors.
      These data and survival analysis plots of breast cancer patients suggest that
      concomitant detection of ADAMTS-12 and fibulin-2 could be a good prognosis marker
      in breast cancer diagnosis. 

PMID- 24457943
TI  - Ultrafast polyene dynamics: the ring opening of 1,3-cyclohexadiene derivatives.
AB  - The light activated ring-opening reaction of the 1,3-cyclohexadiene chromophore
      finds application in optical control, optical switching, optical memory, light
      activated molecular machines, photobiology, photochromic materials, and
      conformation-specific photocatalysts. The development of ultrafast spectroscopic
      methods and powerful computational methods have accelerated the understanding and
      facilitated the application of this important chromophore in a wide range of
      systems. Here we look at the current state of theoretical and experimental
      understanding for the ring-opening reaction of the isolated cyclohexadiene
      molecule and the ring-opening reactions of substituted cyclohexadienes, including
      fulgides, diarylethenes, and provitamin D. 

PMID- 24457944
TI  - The respective role of medical and surgical therapy for enterovesical fistula in
      Crohn's disease.
AB  - GOALS AND BACKGROUND: There are very few reports available on the role of medical
      and surgical therapy for enterovesical fistula (EVF) in Crohn's disease (CD). The
      goal of this study was to investigate the respective role of medical and surgical
      therapy. MATERIALS AND METHODS: Thirty-seven patients with EVF in CD, who were
      consecutively admitted to our institution between 2004 and 2011, underwent
      initial medical treatment. Medical records were abstracted from our prospective
      CD database. We performed a univariate analysis of risk factors for surgery.
      RESULTS: The origin of EVF was ileal (ileovesical fistula, 78.4%) and sigmoidal
      (sigmoidovesical and ileosigmoidovesical fistula, 21.6%). After medical therapy
      (antibiotics, azathioprine, steroids, infliximab, or a combination), 13/37
      (35.1%) patients achieved long-term remission over a mean period of 4.7 years and
      avoided surgery. Surgery was performed in 24/37 (64.9%) patients presenting with
      intractable disease. Univariate analysis showed that the significant risk factors
      for surgery included sigmoid-originated EVF (P=0.019) and concurrent CD
      complications (P=0.001), such as small bowel obstruction, abscess formation,
      enterocutaneous fistula, enteroenteric fistula, and persistent ureteral
      obstruction or urinary tract infection. CONCLUSIONS: For patients with
      ileovesical fistula alone, medical therapy is the first choice. For patients with
      ileovesical fistula accompanied by other CD complications, surgical intervention
      will most likely be needed. Patients with sigmoidovesical or ileosigmoidovesical
      fistula are more likely to require surgery than an uncomplicated ileovesical
      fistula.

PMID- 24457945
TI  - Single-port retroperitoneoscopic pancreatectomy: preliminary results from the
      first 3 patients.
AB  - To date, single-port laparoscopic pancreatic surgery has been rarely reported.
      This study aimed to evaluate the feasibility and safety of single-port
      retroperitoneoscopic pancreatectomy based on the first 3 cases in a single
      center. Three patients with suspected lesions in the distal pancreas underwent
      single-port retroperitoneoscopic pancreatectomy using a conventional
      retroperitoneoscopic pancreatectomy approach. All operations were successfully
      completed utilizing a single port. Operating times were 50, 90, and 150 minutes
      for the 3 cases. There were no complications, and all patients were discharged
      within 7 days after surgery. In conclusion, for selected patients, single-port
      retroperitoneoscopy can be safely utilized for pancreatectomy. 

PMID- 24457947
TI  - Prognostic factors in patients presenting with pleural effusion revealing
      malignancy.
AB  - BACKGROUND: The survival of patients with malignant pleural effusion is
      considered generally poor. Most of the studies reporting results of prognostic
      factors are retrospective, using pleural thoracentesis for diagnosis. The
      objectives of our study were to reveal possible prognostic factors in patients
      initially presenting with undiagnosed pleural effusion proven to be malignant by
      diagnostic thoracoscopy. METHODS: Ninety consecutive patients, 48 of whom were
      male (53%), with a median age of 69 years (range 37-93) and a performance status
      (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven
      to be malignant by thoracoscopy were evaluated. Survival time was defined as the
      time from thoracoscopic diagnosis to death or the last follow-up. A regression
      analysis was used to determine significant clinical and biological prognostic
      factors. RESULTS: Lung carcinoma (44.4%), breast carcinoma (24.4%), and
      mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall
      survival was 11 months (range 0.5-55). The survival of the patients was related
      to the following factors: histology of the primary tumor (p = 0.008), PS (p <
      0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte
      (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L
      ratio. CONCLUSION: The factors affecting survival in our patients were PS,
      primary tumor histology, and the N/L ratio. These factors may help physicians
      select patients for treatment and/or interventional procedures.

PMID- 24457946
TI  - Distinct features in natural history and outcomes of acute hepatitis C.
AB  - BACKGROUND: Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse
      clinical presentations. GOALS: This study was aimed to examine the clinical and
      demographic features as well as outcomes in AHCV patients identified from
      inpatient and outpatient hospital settings. STUDY: Patients with suspected AHCV
      were recruited from Philadelphia VA Medical Center, Hospital of University of
      Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was
      diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C
      virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high
      risk exposure without prior HCV infection, excluding those with human
      immunodeficiency virus infection. Clinical and therapeutic outcomes were
      monitored for at least 6 months. RESULTS: A total of 40 AHCV patients were
      enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and
      whites (73%) with median age of 43 years, diverse risk factors (33% injection
      drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide
      variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin
      levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted
      without therapy in 27%, whereas 50% received interferon alpha-based therapy with
      90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic
      fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies
      (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune
      features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid
      cirrhosis progression in 2 patients. CONCLUSIONS: AHCV is a heterogenous disease
      that requires careful monitoring. The lack of apparent risk factor in high
      proportion of patients and its diverse presentations warrant diagnostic
      vigilance.

PMID- 24457948
TI  - Chiral squaramide-catalysed one-pot enantioselective sulfa-Michael
      addition/thioesterification of thiols with alpha,beta-unsaturated N-acylated
      succinimides.
AB  - A novel highly enantioselective one-pot dithiolation through sulfa-Michael
      addition/thioesterification of thiols with alpha,beta-unsaturated N-acylated
      succinimides catalysed by squaramide has been developed. This organocatalysed
      reaction proceeded well in high to excellent yields (up to >99%) to afford useful
      bioactive beta-sulfated thioester derivatives with high enantioselectivities (up
      to 96% ee). 

PMID- 24457949
TI  - Two modes of exocytosis in an artificial cell.
AB  - The details of exocytosis, the vital cell process of neuronal communication, are
      still under debate with two generally accepted scenarios. The first mode of
      release involves secretory vesicles distending into the cell membrane to release
      the complete vesicle contents. The second involves partial release of the vesicle
      content through an intermittent fusion pore, or an opened or partially distended
      fusion pore. Here we show that both full and partial release can be mimicked with
      a single large-scale cell model for exocytosis composed of material from blebbing
      cell plasma membrane. The apparent switching mechanism for determining the mode
      of release is demonstrated to be related to membrane tension that can be
      differentially induced during artificial exocytosis. These results suggest that
      the partial distension mode might correspond to an extended kiss-and-run
      mechanism of release from secretory cells, which has been proposed as a major
      pathway of exocytosis in neurons and neuroendocrine cells. 

PMID- 24457950
TI  - From label fusion to correspondence fusion: a new approach to unbiased groupwise
      registration.
AB  - Label fusion strategies are used in multi-atlas image segmentation approaches to
      compute a consensus segmentation of an image, given a set of candidate
      segmentations produced by registering the image to a set of atlases [19, 11, 8].
      Effective label fusion strategies, such as local similarity-weighted voting [1,
      13] substantially reduce segmentation errors compared to single-atlas
      segmentation. This paper extends the label fusion idea to the problem of finding
      correspondences across a set of images. Instead of computing a consensus
      segmentation, weighted voting is used to estimate a consensus coordinate map
      between a target image and a reference space. Two variants of the problem are
      considered: (1) where correspondences between a set of atlases are known and are
      propagated to the target image; (2) where correspondences are estimated across a
      set of images without prior knowledge. Evaluation in synthetic data shows that
      correspondences recovered by fusion methods are more accurate than those based on
      registration to a population template. In a 2D example in real MRI data, fusion
      methods result in more consistent mappings between manual segmentations of the
      hippocampus.

PMID- 24457951
TI  - Chymase inhibition attenuates lipopolysaccharide/ d-galactosamine-induced acute
      liver failure in hamsters.
AB  - BACKGROUND/AIMS: Chymase inhibition has been shown to attenuate matrix
      metalloproteinase (MMP)-9 and tumor necrosis factor (TNF)-alpha, both of which
      are associated with the pathogenesis of acute liver failure (ALF). This study
      investigated the effects of the chymase inhibitor TY-51469 on lipopolysaccharide
      (LPS)/D-galactosamine (GalN)-induced ALF in hamsters. METHODS: TY-51469 (10 or 30
      mg/kg) or placebo was administered 1 h before the LPS (160 ug/kg)/GalN (400
      mg/kg) injection. RESULTS: Hepatic chymase activity was significantly increased
      after the LPS/GalN injection, but the significant increase was dose-dependently
      and significantly attenuated by treatment with TY-51469. Significant increases in
      hepatic MMP-9 activity and TNF-alpha concentration were observed after the
      LPS/GalN injection, but these increases were also attenuated by treatment with TY
      51469. Plasma aspartate aminotransferase and alanine aminotransferase activities
      were significantly increased after LPS/GalN injection in the placebo-treated
      group, but the increases were significantly attenuated in the TY-51469-treated
      group. The area of hepatic necrotic after LPS/GalN injection was significantly
      reduced by treatment with TY-51469. Treatment with TY-51469 resulted in
      significant reductions in the hepatic malondialdehyde concentration, mast cell
      numbers, and gene expressions of interleukin-1beta and myeloperoxidase.
      DISCUSSION: Chymase inhibition could be a useful strategy to attenuate LPS/GalN
      induced ALF in hamsters.

PMID- 24457952
TI  - Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27
      (Kip1).
AB  - Functional genomics studies have led to the discovery of a large amount of non
      coding RNAs from the human genome; among them are long non-coding RNAs (lncRNAs).
      Emerging evidence indicates that lncRNAs could have a critical role in the
      regulation of cellular processes such as cell growth and apoptosis as well as
      cancer progression and metastasis. As master gene regulators, lncRNAs are capable
      of forming lncRNA-protein (ribonucleoprotein) complexes to regulate a large
      number of genes. For example, lincRNA-RoR suppresses p53 in response to DNA
      damage through interaction with heterogeneous nuclear ribonucleoprotein I (hnRNP
      I). The present study demonstrates that hnRNP I can also form a functional
      ribonucleoprotein complex with lncRNA urothelial carcinoma-associated 1 (UCA1)
      and increase the UCA1 stability. Of interest, the phosphorylated form of hnRNP I,
      predominantly in the cytoplasm, is responsible for the interaction with UCA1.
      Moreover, although hnRNP I enhances the translation of p27 (Kip1) through
      interaction with the 5'-untranslated region (5'-UTR) of p27 mRNAs, the
      interaction of UCA1 with hnRNP I suppresses the p27 protein level by competitive
      inhibition. In support of this finding, UCA1 has an oncogenic role in breast
      cancer both in vitro and in vivo. Finally, we show a negative correlation between
      p27 and UCA in the breast tumor cancer tissue microarray. Together, our results
      suggest an important role of UCA1 in breast cancer. 

PMID- 24457953
TI  - The interaction between mesenchymal stem cells and steroids during inflammation.
AB  - Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects
      through differentiation and modulation of inflammatory responses. However, the
      relationship between the severity of inflammation and stem cell-mediated tissue
      repair has not been formally investigated. In this study, we applied different
      concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured
      with or without MSCs. As expected, Dex exhibited a classical dose-dependent
      inhibition of T-cell proliferation. Surprisingly, although MSCs also blocked T
      cell proliferation, the presence of Dex unexpectedly showed a dose-dependent
      reversion of T-cell proliferation. This effect of Dex was found to be exerted
      through interfering STAT1 phosphorylation-prompted expression of inducible nitric
      oxide synthase (iNOS). Interestingly, inflammation-induced chemokines in MSCs was
      unaffected. To test the role of inflammation severity in stem cell-mediated
      tissue repair, we employed mice with carbon tetrachloride-induced advanced liver
      fibrosis and found that although MSCs alone were effective, concurrent
      administration of Dex abrogated the therapeutic effects of MSCs on fibrin
      deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as
      T-lymphocyte infiltration, especially IFN-gamma(+)CD4(+) and IL-17A(+)CD4(+)T
      cells. Likewise, iNOS(-/-) MSCs, which produce chemokines but not nitric oxide
      under inflammatory conditions, are ineffective in treating advanced liver
      fibrosis. Therefore, inflammation has a critical role in MSC-mediated tissue
      repair. In addition, concomitant application of MSCs with steroids should be
      avoided. 

PMID- 24457954
TI  - Nox4 and redox signaling mediate TGF-beta-induced endothelial cell apoptosis and
      phenotypic switch.
AB  - Transforming growth factor-beta (TGF-beta) triggers apoptosis in endothelial
      cells, while the mechanisms underlying this action are not entirely understood.
      Using genetic and pharmacological tools, we demonstrated that TGF-beta induced a
      moderate apoptotic response in human cultured endothelial cells, which was
      dependent upon upregulation of the Nox4 NADPH oxidase and production of reactive
      oxygen species (ROS). In contrast, we showed that ectopic expression of Nox4 via
      viral vectors (vNox4) produced an antiapoptotic effect. TGF-beta caused ROS
      dependent p38 activation, whereas inhibition of p38 blunted TGF-beta-induced
      apoptosis. However, vNox4, but not TGF-beta, activated Akt, and inhibition of Akt
      attenuated the antiapoptotic effect of vNox4. Akt activation induced by vNox4 was
      accompanied by inactivation of the protein tyrosine phosphatase-1B (PTP1B)
      function and enhanced vascular endothelial growth factor receptor (VEGFR)-2
      phosphorylation. Moreover, we showed that TGF-beta enhanced Notch signaling and
      increased expression of the arterial marker EphrinB2 in a redox-dependent manner.
      In summary, our results suggest that Nox4 and ROS have pivotal roles in mediating
      TGF-beta-induced endothelial apoptosis and phenotype specification. Redox
      mechanisms may influence endothelial cell functions by modulating p38,
      PTP1B/VEGFR/Akt and Notch signaling pathways. 

PMID- 24457955
TI  - Modulation of apoptosis sensitivity through the interplay with autophagic and
      proteasomal degradation pathways.
AB  - Autophagic and proteasomal degradation constitute the major cellular proteolysis
      pathways. Their physiological and pathophysiological adaptation and perturbation
      modulates the relative abundance of apoptosis-transducing proteins and thereby
      can positively or negatively adjust cell death susceptibility. In addition to
      balancing protein expression amounts, components of the autophagic and
      proteasomal degradation machineries directly interact with and co-regulate
      apoptosis signal transduction. The influence of autophagic and proteasomal
      activity on apoptosis susceptibility is now rapidly gaining more attention as a
      significant modulator of cell death signalling in the context of human health and
      disease. Here we present a concise and critical overview of the latest knowledge
      on the molecular interplay between apoptosis signalling, autophagy and
      proteasomal protein degradation. We highlight that these three pathways
      constitute an intricate signalling triangle that can govern and modulate cell
      fate decisions between death and survival. Owing to rapid research progress in
      recent years, it is now possible to provide detailed insight into the mechanisms
      of pathway crosstalk, common signalling nodes and the role of multi-functional
      proteins in co-regulating both protein degradation and cell death. 

PMID- 24457956
TI  - Integrin inhibition promotes atypical anoikis in glioma cells.
AB  - Integrins regulate cellular adhesion and transmit signals important for cell
      survival, proliferation and motility. They are expressed by glioma cells and may
      contribute to their malignant phenotype. Integrin inhibition may therefore
      represent a promising therapeutic strategy. GL-261 and SMA-560 glioma cells grown
      under standard conditions uniformly detached and formed large cell clusters after
      integrin gene silencing or pharmacological inhibition using EMD-121974, a
      synthetic Arg-Gly-Asp-motif peptide, or GLPG0187, a nonpeptidic integrin
      inhibitor. After 120 h, the clusters induced by integrin inhibition decayed and
      cells died. In contrast, when cells were cultured under stem cell (sphere)
      conditions, no disaggregation became apparent upon integrin inhibition, and cell
      death was not observed. As poly-HEMA-mediated detachment had similar effects on
      cell viability as integrin inhibition, we postulated that cell death may result
      from detachment alone, which was confirmed using various permissive and
      nonpermissive substrates. No surrogate markers of apoptosis were detected and
      electron microscopy confirmed that necrosis represents the dominant morphology of
      detachment-induced cell death. In addition, integrin inhibition resulted in the
      induction of autophagy that represents a survival signal. When integrins were
      inhibited in nonsphere glioma cells, the TGF-beta pathway was strongly impaired,
      whereas no such effect was observed in glioma cells cultured under sphere
      conditions. Cell death induced by integrin inhibition was rescued by the addition
      of recombinant transforming growth factor-beta (TGF-beta) and accelerated by
      exposure to the TGF-beta receptor inhibitor, SD-208. In summary, cell death
      following integrin inhibition is detachment mediated, represents an atypical form
      of anoikis involving necrosis as well as autophagy, and is modulated by TGF-beta
      pathway activity.

PMID- 24457957
TI  - Discrepant NOXA (PMAIP1) transcript and NOXA protein levels: a potential
      Achilles' heel in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with transient
      response to conventional chemotherapy. We here investigated the role of the Bcl-2
      homology domain 3-only protein NOXA for life-death decision in MCL. Surprisingly,
      NOXA (PMAIP1) mRNA and NOXA protein levels were extremely discrepant in MCL
      cells: NOXA mRNA was found to be highly expressed whereas NOXA protein levels
      were low. Chronic active B-cell receptor signaling and to a minor degree cyclin
      D1 overexpression contributed to high NOXA mRNA expression levels in MCL cells.
      The phoshatidyl-inositol-3 kinase/AKT/mammalian target of rapamycin pathway was
      identified as the major downstream signaling pathway involved in the maintenance
      of NOXA gene expression. Interestingly, MCL cells adapt to this constitutive pro
      apoptotic signal by extensive ubiquitination and rapid proteasomal degradation of
      NOXA protein (T1/2~15-30 min). In addition to the proteasome inhibitor
      Bortezomib, we identified the neddylation inhibitor MLN4924 and the fatty acid
      synthase inhibitor Orlistat as potent inducers of NOXA protein expression leading
      to apoptosis in MCL. All inhibitors targeted NOXA protein turnover. In contrast
      to Bortezomib, MLN4924 and Orlistat interfered with the ubiquitination process of
      NOXA protein thereby offering new strategies to kill Bortezomib-resistant MCL
      cells. Our data, therefore, highlight a critical role of NOXA in the balance
      between life and death in MCL. The discrepancy between NOXA transcript and
      protein levels is essential for sensitivity of MCL to ubiquitin-proteasome system
      inhibitors and could therefore provide a druggable Achilles' heel of MCL cells. 

PMID- 24457958
TI  - Antitumor activity of [Pt(O,O'-acac)(gamma-acac)(DMS)] in mouse xenograft model
      of breast cancer.
AB  - The higher and selective cytotoxicity of [Pt(O,O'-acac)(gamma-acac)(DMS)] toward
      cancer cell in both immortalized cell lines and in breast cancer cells in primary
      cultures, stimulated a pre-clinical study so as to evaluate its therapeutic
      potential in vivo. The efficacy of [Pt(O,O'-acac)(gamma-acac)(DMS)] was assessed
      using a xenograft model of breast cancer developed by injection of MCF-7 cells in
      the flank of BALB/c nude mice. Treatment of solid tumor-bearing mice with
      [Pt(O,O'-acac)(gamma-acac)(DMS)] induced up to 50% reduction of tumor mass
      compared with an average 10% inhibition recorded in cisplatin-treated animals.
      Thus, chemotherapy with [Pt(O,O'-acac)(gamma-acac)(DMS)] was much more effective
      than cisplatin. We also demonstrated enhanced in vivo pharmacokinetics,
      biodistribution and tolerability of [Pt(O,O'-acac)(gamma-acac)(DMS)] when
      compared with cisplatin administered in Wistar rats. Pharmacokinetics studies
      with [Pt(O,O'-acac)(gamma-acac)(DMS)] revealed prolonged Pt persistence in
      systemic blood circulation and decreased nefrotoxicity and hepatotoxicity, major
      target sites of cisplatin toxicity. Overall, [Pt(O,O'-acac)(gamma-acac)(DMS)]
      turned out to be extremely promising in terms of greater in vivo anticancer
      activity, reduced nephrotoxicity and acute toxicity compared with cisplatin. 

PMID- 24457959
TI  - The fine-tuning of TRAF2-GSTP1-1 interaction: effect of ligand binding and in
      situ detection of the complex.
AB  - We provide the first biochemical evidence of a direct interaction between the
      glutathione transferase P1-1 (GSTP1-1) and the TRAF domain of TNF receptor
      associated factor 2 (TRAF2), and describe how ligand binding modulates such an
      equilibrium. The dissociation constant of the heterocomplex is K(d)=0.3 MUM;
      however the binding affinity strongly decreases when the active site of GSTP1-1
      is occupied by the substrate GSH (K(d)>=2.6 MUM) or is inactivated by oxidation
      (Kd=1.7 MUM). This indicates that GSTP1-1's TRAF2-binding region involves the GSH
      binding site. The GSTP1-1 inhibitor NBDHEX further decreases the complex's
      binding affinity, as compared with when GSH is the only ligand; this suggests
      that the hydrophobic portion of the GSTP1-1 active site also contributes to the
      interaction. We therefore hypothesize that TRAF2 binding inactivates GSTP1-1;
      however, analysis of the data, using a model taking into account the dimeric
      nature of GSTP1-1, suggests that GSTP1-1 engages only one subunit in the complex,
      whereas the second subunit maintains the catalytic activity or binds to other
      proteins. We also analyzed GSTP1-1's association with TRAF2 at the cellular
      level. The TRAF2-GSTP1-1 complex was constitutively present in U-2OS cells, but
      strongly decreased in S, G2 and M phases. Thus the interaction appears regulated
      in a cell cycle-dependent manner. The variations in the levels of individual
      proteins seem too limited to explain the complex's drastic decline observed in
      cells progressing from the G0/G1 to the S-G2-M phases. Moreover, GSH's
      intracellular content was so high that it always saturated GSTP1-1.
      Interestingly, the addition of NBDHEX maintains the TRAF2-GSTP1-1 complex at low
      levels, thus causing a prolonged cell cycle arrest in the G2/M phase. Overall,
      these findings suggest that a reversible sequestration of TRAF2 into the complex
      may be crucial for cell cycle progression and that multiple factors are involved
      in the fine-tuning of this interaction.

PMID- 24457960
TI  - Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4)
      by casein kinase 2 in prostate cancer cells.
AB  - The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor
      suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2
      (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents
      or anticancer drugs. However, the mechanistic understanding on how CK2 supports
      survival is far from complete. In this work, we demonstrate both in rat and
      humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii)
      phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel
      different levels of CK2-dependent regulation of Par-4 between species. In rats,
      the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par
      4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In
      humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of
      the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation
      at residue S231. Furthermore, we show that human Par-4 residue S231 is highly
      phosphorylated in prostate cancer cells as compared with their normal
      counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by
      CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par
      4 seems a critical target of CK2 that could be exploited for the development of
      new anticancer drugs. 

PMID- 24457961
TI  - Cross-regulation of Connexin43 and beta-catenin influences differentiation of
      human neural progenitor cells.
AB  - Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ)
      protein and it is strongly associated with the regulation of cell cycle
      progression. Emerging roles for Cx43 in cell adhesion and migration during neural
      differentiation have also been recently recognized, and this has emphasized the
      involvement of Cx43 in different physiological process beyond its role as a GJ
      protein. In this study, we explore the function of Cx43 in the differentiation of
      human neural progenitor cells (hNPCs) using viral vectors that mediate the
      overexpression or knockdown of the protein. Results showed that in the absence of
      this protein fetal cortex-derived hNPCs differentiated toward a neuronal
      phenotype at expenses of a glial phenotype. Furthermore, the silencing of Cx43
      did not affect hNPC proliferation rate or numbers of apoptotic cells. The
      increase in the number of neurons was not recapitulated when GJ intercellular
      communications were pharmacologically blocked, and this suggested that Cx43 was
      influencing hNPCs differentiation with a GJ-independent effect. In addition, Cx43
      knockdown significantly increased beta-catenin signaling, which has been shown to
      regulate the transcription of pro-neuronal genes during embryonic neural
      development. Our results add further support to the hypothesis that Cx43 protein
      itself regulates key signaling pathways during development and neurogenesis
      beyond its role as GJ protein. 

PMID- 24457963
TI  - c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction
      in vivo.
AB  - Altered synaptic function is considered one of the first features of Alzheimer
      disease (AD). Currently, no treatment is available to prevent the dysfunction of
      excitatory synapses in AD. Identification of the key modulators of synaptopathy
      is of particular significance in the treatment of AD. We here characterized the
      pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal
      kinase (JNK) is activated at the spine prior to the onset of cognitive
      impairment. The specific inhibition of JNK, with its specific inhibiting peptide
      D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the
      loss of postsynaptic proteins and glutamate receptors from the postsynaptic
      density and the reduction in size of excitatory synapses, reverting their
      dysfunction. This set of data reveals that JNK is a key signaling pathway in AD
      synaptic injury and that its specific inhibition offers an innovative therapeutic
      strategy to prevent spine degeneration in AD. 

PMID- 24457962
TI  - Clinical update on cancer: molecular oncology of head and neck cancer.
AB  - Head and neck cancers encompass a heterogeneous group of tumours that, in
      general, are biologically aggressive in nature. These cancers remain difficult to
      treat and treatment can cause severe, long-term side effects. For patients who
      are not cured by surgery and/or (chemo)radiotherapy, there are few effective
      treatment options. Targeted therapies and predictive biomarkers are urgently
      needed in order to improve the management and minimise the treatment toxicity,
      and to allow selection of patients who are likely to benefit from both
      nonselective and targeted therapies. This clinical update aims to provide an
      insight into the current understanding of the molecular pathogenesis of the
      disease, and explores the novel therapies under development and in clinical
      trials. 

PMID- 24457964
TI  - Interleukin-1beta promotes hypoxia-induced apoptosis of glioblastoma cells by
      inhibiting hypoxia-inducible factor-1 mediated adrenomedullin production.
AB  - Glioblastoma is the most common brain tumor in adults. Advanced glioblastomas
      normally contain hypoxic areas. The primary cellular responses to hypoxia are
      generally mediated by the transcription factor hypoxia-inducible factor 1 (HIF
      1). Interleukin-1beta (IL-1beta) is a cytokine that is often present in the
      glioblastoma microenvironment and is known to be a modulator of glioblastoma
      progression. However, the role of IL-1beta in regulating glioblastoma progression
      is still controversial. In this study, we found that in the human glioblastoma
      cell lines U87MG and U138MG, IL-1beta inhibits the transactivation activity of
      HIF-1 by promoting the ubiquitin-independent proteasomal degradation of the
      oxygen-labile alpha-subunit of HIF-1 and downregulates the expression of the HIF
      1 target gene adrenomedullin (AM). Apoptosis and MTT (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide) assays showed that AM protects glioblastoma
      cells against hypoxia-induced apoptosis in a dose-dependent manner. Thus, in the
      presence of IL-1beta more glioblastoma cells undergo hypoxia-induced cell death.
      Our findings suggest that when estimating the influence of IL-1beta on the
      prognosis of glioblastoma patients, factors such as the degree of hypoxia, the
      expression levels of HIF-1 and AM should be taken into consideration. For the AM
      producing glioblastoma cells, IL-1beta represents a potent apoptosis inducer. 

PMID- 24457965
TI  - ROS-PIASgamma cross talk channelizes ATM signaling from resistance to apoptosis
      during chemosensitization of resistant tumors.
AB  - With the existing knowledge of ATM's role in therapeutic resistance, the present
      study aimed at identifying the molecular mechanisms that influence ATM to
      oscillate between chemoresistance and chemosensitivity. We observed that the
      redox status of tumors functions as a major determinant of ATM-dependent
      'resistance-to-apoptosis' molecular switch. At a low reactive oxygen species
      (ROS) condition during genotoxic insult, the ATM/sumoylated-IKKgamma interaction
      induced NFkappaB activation that resisted JNK-mediated apoptosis, whereas
      increasing cellular ROS restored ATM/JNK apoptotic signaling. A search for the
      upstream missing link revealed that high ROS induces oxidation and ubiquitin
      mediated degradation of PIASgamma, thereby disrupting PIASgamma-IKKgamma cross
      talk, a pre-requisite for IKKgamma sumoylation and subsequent NFkappaB
      activation. Interruption in the PIASgamma-mediated resistance pathway channels
      ATM signaling toward ATM/JNK pro-death circuitry. These in vitro results also
      translated to sensitive and resistant tumor allograft mouse models in which low
      ROS-induced resistance was over-ruled in PIASgamma knockout tumors, while its
      overexpression inhibited high ROS-dependent apoptotic cues. Cumulatively, our
      findings identified an unappreciated yet critical combinatorial function of
      cellular ROS and PIASgamma in regulating ATM-mediated chemosensitization of
      resistant tumors. Thus, therapeutic strategies employing ROS upregulation to
      inhibit PIASgamma during genotoxic therapy may, in future, help to eliminate the
      problems of NFkappaB-mediated tumor drug resistance. 

PMID- 24457966
TI  - Stress-induced RNASET2 overexpression mediates melanocyte apoptosis via the TRAF2
      pathway in vitro.
AB  - The recent genome-wide association study identified a link between vitiligo and
      genetic variants in the ribonuclease T2 (RNASET2) gene; however, the functional
      roles of RNASET2 in vitiligo pathogenesis or in melanocyte apoptosis have yet to
      be determined. The current study was designed to investigate the vitiligo-related
      expression pattern of RNASET2 and its molecular function involving apoptosis
      related signaling proteins and pathways. The results showed overexpression of
      RNASET2 in epidermis specimens from 40 vitiligo patients compared with that from
      matched healthy controls. In addition, in vitro analyses indicated that
      overexpression of RNASET2 was inducible in cultured primary human melanocytes and
      keratinocytes by stress conditions, that is, exposure to UV irradiation, hydrogen
      peroxide, and inflammatory factors, respectively, and led to increased cell
      apoptosis via the tumor necrosis factor receptor-associated factor 2 (TRAF2)
      caspases pathway through the physical interaction of RNASET2 with TRAF2. Thus,
      RNASET2 may contribute to vitiligo pathogenesis by inhibiting TRAF2 expression
      and, as such, RNASET2 may represent a potential therapeutic target of vitiligo. 

PMID- 24457967
TI  - A cell-penetrating peptide based on the interaction between c-Src and connexin43
      reverses glioma stem cell phenotype.
AB  - Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes,
      is downregulated in malignant gliomas. These tumors are composed of a
      heterogeneous population of cells that include many with stem-cell-like
      properties, called glioma stem cells (GSCs), which are highly tumorigenic and
      lack Cx43 expression. Interestingly, restoring Cx43 reverses GSC phenotype and
      consequently reduces their tumorigenicity. In this study, we investigated the
      mechanism by which Cx43 exerts its antitumorigenic effects on GSCs. We have
      focused on the tyrosine kinase c-Src, which interacts with the intracellular
      carboxy tail of Cx43. We found that Cx43 regulates c-Src activity and
      proliferation in human GSCs expanded in adherent culture. Thus, restoring Cx43 in
      GSCs inhibited c-Src activity, which in turn promoted the downregulation of the
      inhibitor of differentiation Id1. Id1 sustains stem cell phenotype as it controls
      the expression of Sox2, responsible for stem cell self-renewal, and promotes
      cadherin switching, which has been associated to epithelial-mesenchymal
      transition. Our results show that both the ectopic expression of Cx43 and the
      inhibition of c-Src reduced Id1, Sox2 expression and promoted the switch from N-
      to E-cadherin, suggesting that Cx43, by inhibiting c-Src, downregulates Id1 with
      the subsequent changes in stem cell phenotype. On the basis of this mechanism, we
      found that a cell-penetrating peptide, containing the region of Cx43 that
      interacts with c-Src, mimics the effect of Cx43 on GSC phenotype, confirming the
      relevance of the interaction between Cx43 and c-Src in the regulation of the
      malignant phenotype and pinpointing this interaction as a promising therapeutic
      target. 

PMID- 24457970
TI  - Artificial intelligence: the future of medicine?

PMID- 24457968
TI  - OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell
      transformation.
AB  - Human cell transformation is a key step for oncogenic development, which involves
      multiple pathways; however, the mechanism remains unclear. To test our hypothesis
      whether cell oncogenic transformation shares some mechanisms with the process of
      reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied
      the relationship among the key factors for promoting or inhibiting iPSC in
      radiation-transformed human epithelial cell lines derived from different tissues
      (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly
      expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell
      lines examined when compared with their non-transformed counterparts. We further
      elucidated the relationship of these factors: the 3p strand of miR-34a directly
      targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and,
      OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a
      specific region of the p63 or p53 promoter. Moreover, we revealed that the
      effects of OCT4 on promoting cell oncogenic transformation were by affecting p63
      and p53. These results support that a positive loop exists in human cells: OCT4
      upregulation as a consequence of inhibition of miR-34a, promotes p63 but
      suppresses p53 expression, which further stimulates OCT4 upregulation by
      downregulating miR-34a. This functional loop contributes significantly to cell
      transformation and, most likely, also to the iPSC process. 

PMID- 24457969
TI  - Role of IGF2BP3 in trophoblast cell invasion and migration.
AB  - The insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) is a member of
      a highly conserved protein family that is expressed specifically in placenta,
      testis and various cancers, but is hardly detectable in normal adult tissues.
      IGF2BP3 has important roles in RNA stabilization and translation, especially
      during early stages of both human and mouse embryogenesis. Placenta is an
      indispensable organ in mammalian reproduction that connects developing fetus to
      the uterine wall, and is responsible for nutrient uptake, waste elimination and
      gas exchange. Fetus development in the maternal uterine cavity depends on the
      specialized functional trophoblast. Whether IGF2BP3 plays a role in trophoblast
      differentiation during placental development has never been examined. The data
      obtained in this study revealed that IGF2BP3 was highly expressed in human
      placental villi during early pregnancy, especially in cytotrophoblast cells
      (CTBs) and trophoblast column, but a much lower level of IGF2BP3 was detected in
      the third trimester placental villi. Furthermore, the expression level of IGF2BP3
      in pre-eclamptic (PE) placentas was significantly lower than the gestational age
      matched normal placentas. The role of IGF2BP3 in human trophoblast
      differentiation was shown by in vitro cell invasion and migration assays and an
      ex vivo explant culture model. Our data support a role of IGF2BP3 in promoting
      trophoblast invasion and suggest that abnormal expression of IGF2BP3 might be
      associated with the etiology of PE. 

PMID- 24457971
TI  - Slide preparation method to preserve three-dimensional chromatin architecture of
      testicular germ cells.
AB  - During testicular germ cell differentiation, the structure of nuclear chromatin
      dynamically changes. The following describes a method designed to preserve the
      three-dimensional chromatin arrangement of testicular germ cells found in mice;
      this method has been termed as the three-dimensional (3D) slide method. In this
      method, testicular tubules are directly treated with a permeabilization step that
      removes cytoplasmic material, followed by a fixation step that fixes nuclear
      materials. Tubules are then dissociated, the cell suspension is cytospun, and
      cells adhere to slides. This method improves sensitivity towards detection of
      subnuclear structures and is applicable for immunofluorescence, DNA, and RNA
      fluorescence in situ hybridization (FISH) and the combination of these detection
      methods. As an example of a possible application of the 3D slide method, a Cot-1
      RNA FISH is shown to detect nascent RNAs. The 3D slide method will facilitate the
      detailed examination of spatial relationships between chromatin structure, DNA,
      and RNA during testicular germ cell differentiation. 

PMID- 24457973
TI  - The alternate triad motif of the poly(ADP-ribose) polymerase-like domain of the
      human zinc finger antiviral protein is essential for its antiviral activity.
AB  - The human zinc finger antiviral protein (hZAP) gene is spliced to yield a short
      (hZAP-S) and a long (hZAP-L) isoform. The long isoform possesses a poly(ADP
      ribose) polymerase (PARP)-like domain in its C-terminus predicted to be inactive
      due to alterations in its triad motif compared with bona fide PARPs. Using
      Sindbis virus as prototype member of alphaviruses we confirmed that hZAP-L is a
      more potent inhibitor of alphaviruses than hZAP-S. Specific small interfering RNA
      knockdown of hZAP-L but not hZAP-S demonstrated a role of endogenous hZAP-L in
      restriction of alphavirus replication. Whilst single amino-acid substitutions in
      the triad motif of hZAP-L's PARP-like domain reduced the antiviral activity,
      exchange of all three triad motif residues to alanine or to the amino acids of
      active PARPs virtually abolished the antiviral effect. Contrary to previous
      assumptions, these results indicate an essential function of the PARP-like domain
      in hZAP-L's antiviral activity. 

PMID- 24457972
TI  - Maternal serum placental growth factor (PlGF) isoforms 1 and 2 at 11-13 weeks'
      gestation in normal and pathological pregnancies.
AB  - OBJECTIVE: To compare the maternal serum concentration of placental growth factor
      1 (PlGF-1) and PlGF-2 at 11-13 weeks' gestation in normal pregnancies and in
      those complicated by preeclampsia (PE), delivery of small for gestational age
      (SGA) neonates and fetal trisomies 21, 18 and 13. METHODS: Serum PlGF-1 and PlGF
      2 were measured in 270 pathological pregnancies (PE, n = 80; SGA, n = 80; trisomy
      21, n = 44; trisomy 18, n = 38; trisomy 13, n = 28) and 590 normal controls. The
      values were expressed as multiple of the median (MoM) after adjustment for
      maternal characteristics and corrected for adverse pregnancy outcomes and the
      median MoM values in each pathological pregnancy were compared to the normal
      group. RESULTS: There were significant contributions to PlGF-1 and PlGF-2 from
      gestational age, smoking and racial origin. In addition, there were significant
      contributions to PlGF-1 from parity and method of conception. The median MoM of
      PlGF-1 and PlGF-2 was significantly decreased in PE (0.783 and 0.916 MoM), SGA
      (0.891 and 0.851 MoM), trisomy 21 (0.609 and 0.749 MoM), trisomy 18 (0.529 and
      0.730 MoM) and trisomy 13 (0.373 and 0.699 MoM). CONCLUSIONS: In pathological
      pregnancies, except SGA, the decrease in serum PlGF-1 at 11-13 weeks' gestation
      is more marked than the decrease in PlGF-2.

PMID- 24457974
TI  - Bagaza virus and Israel turkey meningoencephalomyelitis virus are a single virus
      species.
AB  - Bagaza virus (BAGV) and Israel turkey meningoencephalomyelitis virus (ITV) are
      classified in the genus Flavivirus of the family Flaviviridae. Serologically,
      they are closely related, belonging to the Ntaya serocomplex. Nucleotide
      sequences available to date consist of several complete sequences of BAGV
      isolates, but only partial sequences of ITV isolates. Sequence comparisons of
      partial envelope (E) and NS5 regions reveal a close genetic relationship between
      these viruses. Despite this, BAGV and ITV are considered as separate virus
      species in the database of the International Committee on Taxonomy of Viruses. In
      this work, complete nucleotide sequences for five ITV isolates are provided,
      thereby permitting a phylogenetic comparison with other complete sequences of
      flaviviruses in the Ntaya serogroup. We conclude that BAGV and ITV are the same
      virus species and propose that both viruses be designated by a new unified name:
      Avian meningoencephalomyelitis virus. 

PMID- 24457976
TI  - A novel manganese-doped large polyoxotitanate nanocluster.
AB  - A large manganese-doped polyoxotitanate nanocluster Ti28MnO38(OEt)40H2, has been
      synthesized solvothermally. Its structure is arranged around the four-coordinate
      Mn(2+) dopant atom in a Keggin-type structure. A significant reduction of the
      band gap relative to that of undoped polyoxotitanate clusters is observed. 

PMID- 24457975
TI  - Dynamic reassortments and genetic heterogeneity of the human-infecting influenza
      A (H7N9) virus.
AB  - Influenza A (H7N9) virus has been causing human infections in China since
      February 2013, raising serious concerns of potential pandemics. Previous studies
      demonstrate that human infection is directly linked to live animal markets, and
      that the internal genes of the virus are derived from H9N2 viruses circulating in
      the Yangtze River Delta area in Eastern China. Here following analysis of 109
      viruses, we show a much higher genetic heterogeneity of the H7N9 viruses than
      previously reported, with a total of 27 newly designated genotypes. Phylogenetic
      and genealogical inferences reveal that genotypes G0 and G2.6 dominantly co
      circulate within poultry, with most human isolates belonging to the genotype G0.
      G0 viruses are also responsible for the inter- and intra-province transmissions,
      leading to the genesis of novel genotypes. These observations suggest the
      province-specific H9N2 virus gene pools increase the genetic diversity of H7N9
      via dynamic reassortments and also imply that G0 has not gained overwhelming
      fitness and the virus continues to undergo reassortment. 

PMID- 24457977
TI  - Intravitreal bevacizumab for postoperative recurrent vitreous hemorrhage after
      vitrectomy for proliferative diabetic retinopathy.
AB  - PURPOSE: To describe the experience of authors using intravitreal bevacizumab
      (IVB) for eyes with recurrent vitreous hemorrhage (VH) after vitrectomy for
      proliferative diabetic retinopathy. METHODS: Chart review was performed on
      eligible eyes from the Illinois Retina Associates' patient database that had at
      least 6 months of follow-up after receiving IVB in the operative eye for
      recurrent VH after vitrectomy for proliferative diabetic retinopathy. RESULTS:
      Twelve eyes of nine patients were included in the study and none required repeat
      vitrectomy for recurrent VH. Mean follow-up was 22 months (range, 8-42). A mean
      of 8.1 IVB (range, 1-18) were given. The mean number of recurrent VH was 4
      (range, 2-8), and a mean of 3.5 of these VHs (range, 1-8) were clear at the
      appointment after an injection, typically in 4 to 6 weeks. Patients with history
      of multiple recurrent VH received prophylactic IVB, and repeated injections at
      regular intervals were associated with increased time period without recurrent
      VH. CONCLUSION: Intravitreal bevacizumab was a safe and effective adjunct in this
      series for the management of recurrent VH after vitrectomy for proliferative
      diabetic retinopathy. No patients required repeat vitrectomy for recurrent VH,
      and prophylactic IVB was associated with longer periods of clear vitreous in the
      late postoperative period.

PMID- 24457978
TI  - Diameter of retinal vessels in patients with diabetic macular edema is not
      altered by intravitreal ranibizumab (lucentis).
AB  - PURPOSE: To investigate the effect(s) of intravitreally injected ranibizumab on
      retinal vessel diameter in patients with diabetic macular edema. METHODS:
      Participants of this prospective study were 14 men and 16 women (30 eyes) aged 60
      +/- 11 years (mean +/- standard deviation), all with clinically significant
      diabetic macular edema. Treatment comprised 3 intravitreal injections of
      ranibizumab given at 4-week intervals. Examinations were conducted before the
      first (baseline), before the second (Month 1), before the third (Month 2)
      injections, and 3 months after baseline (Month 3). Measured parameters included
      systemic blood pressure, static retinal vessel analysis (central retinal artery
      equivalent and central retinal vein equivalent), and dynamic retinal vessel
      analysis, as measured by the change in vessel diameter in response to flicker
      stimulation during three measurement cycles. Flicker stimulation was accomplished
      using a 50-second baseline recording, followed by an online measurement during 20
      second flicker stimulation and 80-second online measurements in both arteriolar
      and venular vessel segments. RESULTS: Static retinal vessel analysis showed a
      reduction of central retinal artery equivalent from 186.25 +/- 51.40 MUm
      (baseline) to 173.20 +/- 22.2 MUm (Month 1), to 174.30 +/- 27.30 MUm (Month 2),
      and to 170.56 +/- 22.89 MUm (Month 3), none of which was statistically
      significant (P = 0.23, 0.12, and 0.14, respectively). Central retinal vein
      equivalent was reduced from 216.21 +/- 25.0 MUm (baseline) to 214.48 +/- 25.4 MUm
      (Month 1), to 214.80 +/- 24.30 MUm (Month 2), and to 211.41 +/- 24.30 MUm (Month
      3), revealing no statistically significant differences between examination time
      points (P = 0.54, 0.06, and 0.24, respectively). Dynamic vessel analysis yielded
      a mean retinal arterial diameter change of +1.47% +/- 2.3 (baseline), +1.91% +/-
      2.5 (Month 1), +1.76% +/- 2.2 (Month 2), and +1.66% +/- 2.1 (Month 3), none of
      which showed statistically significant differences (P = 0.32, 0.49, and 0.70,
      respectively). Mean retinal venous diameter changes were +3.15% +/- 1.7
      (baseline), +3.7% +/- 2.3 (Month 1), +4.0% +/- 2.0 (Month 2), and +4.95% +/- 1.9
      (Month 3), none of which showed statistically significant differences (P = 0.12,
      0.17, and 0.14, respectively). Central retinal thickness, as measured by spectral
      domain optical coherence tomography, decreased significantly from 435.2 +/- 131.8
      MUm (baseline) to 372.3 +/- 142.8 MUm (Month 3), P = 0.01. Regression analysis of
      arteriolar and venular diameters indicated that there was no significant
      correlation between these 2 parameters (r = 0.053; P = 0.835 and r = 0.06; P =
      0.817, respectively). Also, no significant correlation was observed between the
      difference in the central retinal thickness and change in arteriolar or venular
      dilatation (r = 0.291, P = 0.241 and r = 0.06, P = 0.435, respectively).
      CONCLUSION: Intravitreally applied ranibizumab did not significantly affect
      retinal vessel diameter in patients with diabetic macular edema. Decline in the
      central foveal thickness after ranibizumab therapy, as measured by spectral
      domain optical coherence tomography, was not linked to any change in retinal
      vessel diameter or dilatatory response, neither for arterioles nor venules.

PMID- 24457980
TI  - Coloseminal fistula complicating sigmoid diverticulitis.
AB  - We report on a 32-year-old man with a history of chronic lower abdominal pain and
      urogenital symptoms, leading to the diagnosis of coloseminal fistula complicating
      diverticular disease. We reviewed the literature on this rare clinical entity and
      would like to stress the role of pelvic imaging with rectal contrast to
      investigate complicated forms of diverticular disease.

PMID- 24457979
TI  - Upregulation of KCNQ1/KCNE1 K+ channels by Klotho.
AB  - Klotho is a transmembrane protein expressed primarily in kidney, parathyroid
      gland, and choroid plexus. The extracellular domain could be cleaved off and
      released into the systemic circulation. Klotho is in part effective as beta
      glucuronidase regulating protein stability in the cell membrane. Klotho is a
      major determinant of aging and life span.Overexpression of Klotho increases and
      Klotho deficiency decreases life span. Klotho deficiency may further result in
      hearing loss and cardiac arrhythmia. The present study explored whether Klotho
      modifies activity and protein abundance of KCNQ1/KCNE1, a K(+) channel required
      for proper hearing and cardiac repolarization. To this end, cRNA encoding
      KCNQ1/KCNE1 was injected in Xenopus oocytes with or without additional injection
      of cRNA encoding Klotho. KCNQ1/KCNE1 expressing oocytes were treated with human
      recombinant Klotho protein (30 ng/mL) for 24 h. Moreover, oocytes which express
      both KCNQ1/KCNE1 and Klotho were treated with 10 MUM DSA L (D-saccharic acid-1,4
      lactone), a beta-glucuronidase inhibitor. The KCNQ1/KCNE1 depolarization-induced
      current (I(Ks)) was determined utilizing dual electrode voltage clamp, while
      KCNQ1/KCNE1 protein abundance in the cell membrane was visualized utilizing
      specific antibody binding and quantified by chemiluminescence. KCNQ1/KCNE1
      channel activity and KCNQ1/KCNE1 protein abundance were upregulated by
      coexpression of Klotho. The effect was mimicked by treatment with human
      recombinant Klotho protein (30 ng/mL) and inhibited by DSA L (10 MUM). In
      conclusion, Klotho upregulates KCNQ1/KCNE1 channel activity by "mainly" enhancing
      channel protein abundance in the plasma cell membrane, an effect at least
      partially mediated through the beta-glucuronidase activity of Klotho protein.

PMID- 24457981
TI  - Water-soluble polymers, solid polymer membranes, and coated fibres as smart
      sensory materials for the naked eye detection and quantification of TNT in
      aqueous media.
AB  - This study developed sensory polymeric materials for the colorimetric sensing of
      TNT in aqueous media. Solid films and coated fabrics permitted the detection of
      TNT, through colour change, and its quantification, by taking a picture of the
      materials and processing their RGB parameters to define the evolved colour. 

PMID- 24457982
TI  - Variation of the coordination environment and its effect on the white light
      emission properties in a Mn-doped ZnO-ZnS complex structure.
AB  - Mn-doped ZnO-ZnS complex nanocrystals were fabricated through coating of
      dodecanethiol on Mn-doped ZnO nanocrystals. The relationship between the
      component of white light emission and the coordination environments of Mn-dopants
      were experimentally investigated. It was shown that Mn ions mainly formed
      Mn(3+)O6 octahedra in as prepared Mn-doped ZnO, while the Mn(3+) ions on the
      surface of ZnO transferred into Mn(2+) ions at the interface between ZnO and ZnS
      after dodecanethiol coating. The Mn(2+)S4 tetrahedron density and the orange
      emission intensity increased upon enhancing the dodecanethiol content. These
      results provide an alternative way to optimize the white emission spectrum from
      nanocrystals of Mn-doped ZnS-ZnO complex structures through modulation of the
      coordination environment of Mn ions. 

PMID- 24457983
TI  - Psychosomatics: past, present and future.

PMID- 24457984
TI  - The frequency and prognostic impact of fever following transcatheter aortic valve
      implantation.
AB  - OBJECTIVES: This study sought to explore the frequency and prognostic
      implications of infectious and noninfectious fever following transcatheter aortic
      valve implantation (TAVI). METHODS: We performed a retrospective cohort study
      including 194 consecutive patients who underwent TAVI at our institution. We
      identified and characterized all patients who developed fever within the first 72
      h following the procedure. We determined the etiology of the fevers (infectious
      vs. noninfectious) and assessed their impact on in-hospital complications and 1
      year mortality. RESULTS: Following TAVI, 65 (33.5%) patients had fever (mean age
      83.7 +/- 3.8 years, 70.2% female). An infectious etiology was evident in only 17
      of the 65 patients (26.1%) with fever, mainly due to pneumonia (52.9%) and a
      urinary tract infection (41.2%). No significant difference was observed in
      baseline characteristics, the mean fever temperature/duration, or signs of
      inflammatory response between infectious and noninfectious fevers. The mean
      hospital duration was longer (7 +/- 4.8 days vs. 4.7 +/- 2.4 days, p = 0.01)
      among patients with an infectious fever; however, fever had no impact on the 1
      year mortality rate (5.9 and 4.5%, respectively, p = 0.71). CONCLUSIONS: Our
      study demonstrates that, although fever was a common phenomenon after TAVI, it
      represented an infectious complication only in a minority of cases. Nevertheless,
      fever, infectious or not, had no impact on the 1-year mortality rate following
      TAVI.

PMID- 24457985
TI  - Exercise capacity and physical activity in patients with COPD and healthy
      subjects classified as Medical Research Council dyspnea scale grade 2.
AB  - PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) are often
      classified by Medical Research Council (MRC) dyspnea grade and comparisons thus
      made to healthy individuals. The MRC grade of a healthy population is assumed to
      be grade 1, although this may be inaccurate. Physical activity and exercise
      capacity are not well-defined for those with MRC grade 2. This study was
      undertaken to establish whether there are differences in physical activity and
      exercise capacity between individuals with COPD and healthy controls, who have
      all assessed themselves as MRC grade 2. METHODS: Patients with COPD (n = 83) and
      19 healthy controls, with a self-selected MRC grade of 2, completed the
      Incremental Shuttle Walk Test (ISWT) and wore a SenseWear (BodyMedia, Pittsburgh,
      PA) activity monitor for 12 hours for 2 weekdays. RESULTS: Adjusting for age,
      step count and ISWT were significantly reduced for those with COPD, compared with
      healthy controls (P < .05). Patients with COPD achieved mean (SD) 425.5 (131.3) m
      on ISWT and took 6022 (3276) steps per day compared with 647.8 (146.3) m and 9462
      (4141) steps per day for healthy controls. For subjects achieving 10 000 steps
      per day, 8 (42.11%) healthy controls achieved this level compared with 7 (8.43%)
      patients with COPD (P < .01). CONCLUSIONS: Healthy individuals may report
      functional limitations and categorize themselves as MRC grade 2. However, despite
      both groups subjectively considering themselves similarly functionally limited,
      exercise capacity and physical activity were significantly reduced in patients
      with COPD compared with healthy participants. This highlights the importance of
      early interventions to increase physical performance and prevent functional
      decline for patients with COPD.

PMID- 24457986
TI  - Management of liver trauma in Kuwait.
AB  - OBJECTIVES: The aim of this study was to introduce the concept of non-operative
      management (NOM) for blunt liver trauma by establishing a protocol and a
      prospective Liver Trauma Registry in Kuwait. SUBJECTS AND METHODS: A prospective
      Liver Trauma Registry was started in 4 hospitals and it included 117 patients who
      had sustained blunt liver trauma (94 men and 23 women). Unstable patients were
      taken to surgery while stable patients were managed conservatively regardless of
      the grade of liver injury. High-grade (III-VI) liver injuries were managed in
      collaboration with the liver surgery specialist. RESULTS: The mean age of the 117
      patients was 29.02 +/- 11.18 years (range 7-63). NOM was successful in 94 (96%)
      patients and failed in 4 (4%) (these 4 then underwent successful surgery).
      Nineteen (16.2%) were unstable and underwent surgery immediately; 15 (79%) of
      them survived (they had had grade III-V injuries) and 4 died (2 with grade V
      injuries and 2 with grade VI injuries). Perihepatic packing was necessary in 8/19
      (42%) patients. The overall mortality was 3.4% (4/117). CONCLUSIONS: This study
      showed that NOM was successful in a majority of patients with blunt liver trauma.
      In addition, it confirmed that the magnitude of liver injury and haemoperitoneum
      did not preclude NOM as long as the patient was haemodynamically stable.

PMID- 24457987
TI  - Vertically integrated translational studies of PDX1 as a therapeutic target for
      pancreatic cancer via a novel bifunctional RNAi platform.
AB  - RNA interference (RNAi) represents a powerful, new tool for scientific
      investigation as well as a promising new form of targeted gene therapy, with
      applications currently in clinical trials. Bifunctional short hairpin RNA (shRNA)
      are synthetic RNAi molecules, engineered to utilize multiple endogenous RNAi
      pathways to specifically silence target genes. Pancreatic and duodenal homeobox 1
      (PDX1) is a key regulator of pancreatic development, beta-cell differentiation,
      normal beta-cell function and pancreatic cancer. Our aim is to review the process
      of identifying PDX1 as a specific, potential RNAi target in pancreatic cancer, as
      well as the underlying mechanisms and various forms of RNAi, with subsequent
      testing and development of PDX1-targeted bifunctional shRNA therapy. 

PMID- 24457988
TI  - Critical role of miR-10b in transforming growth factor-beta1-induced epithelial
      mesenchymal transition in breast cancer.
AB  - Epithelial-mesenchymal transition (EMT) is a key process in the tumor metastatic
      cascade that is characterized by the loss of cell-cell junctions and cell
      polarity, resulting in the acquisition of migratory and invasive properties.
      Recent evidence showed that altered microRNA-10b (miR-10b) expression was
      implicated in the occurrence of EMT of breast cancer. However, the exact role and
      underlying mechanisms of miR-10b in the EMT of breast cancer still remain
      unknown. In this study, miR-10b was found to be upregulated in breast cancer
      tissues and breast cancer cell lines and the expression of miR-10b was shown to
      be closely correlated with aggressiveness in breast cancer. Treating breast
      cancer cells with the miR-10b inhibitor increased E-cadherin expression while
      decreasing vimentin expression. At the same time, on inhibition of miR-10b, the
      invasion and proliferation ability of breast cancer cells also decreased.
      Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that
      induces EMT in multiple cell types. Here, we identified miR-10b as a target gene
      of TGF-beta1. The expression of miR-10b increased during TGF-beta1-induced EMT of
      breast cancer cells. Further study showed that inhibition of miR-10b expression
      partially reversed the EMT, invasion and proliferation induced by TGF-beta1 in
      breast cancer cells. Taken together, these results demonstrated a novel function
      for miR-10b in TGF-beta1-induced EMT in breast cancer and increased their
      metastatic potential. MiR-10b might become a possible target for gene therapy in
      breast cancer. 

PMID- 24457990
TI  - Total synthesis of alkyl citrate natural products.
AB  - This review highlights the synthesis of members of the alkyl citrate family of
      natural products. The focus is on the stereoselective construction of the alkyl
      citrate moiety common to these compounds. 

PMID- 24457989
TI  - Safety and effects of the vector for the Leber hereditary optic neuropathy gene
      therapy clinical trial.
AB  - IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic
      neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide
      dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the
      safety and effects of the gene therapy vector to be used in a proposed gene
      therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments,
      we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic
      code for import into mitochondria. The protein was targeted into the organelle by
      agency of a targeting sequence (allotopic expression). The gene was packaged into
      adeno-associated viral vectors and then vitreally injected into rodent, nonhuman
      primate, and ex vivo human eyes that underwent testing for expression and
      integration by immunohistochemical analysis and blue native polyacrylamide gel
      electrophoresis. During serial follow-up, the animal eyes underwent fundus
      photography, optical coherence tomography, and multifocal or pattern
      electroretinography. We tested for rescue of visual loss in rodent eyes also
      injected with a mutant G11778A ND4 homologue responsible for most cases of LHON.
      EXPOSURE Ocular infection with recombinant adeno-associated viral vectors
      containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES
      Expression of human ND4 and rescue of optic neuropathy induced by mutant human
      ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion
      cells by 1 week after injection and ND4 integrated into the mouse complex I. In
      rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4
      prevented defective adenosine triphosphate synthesis, suppressed visual loss,
      reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the
      optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in
      most retinal ganglion cells. Primates undergoing vitreal injection with the ND4
      test article and followed up for 3 months had no serious adverse reactions.
      CONCLUSIONS AND RELEVANCE Expression of our allotopic ND4 vector in the ex vivo
      human eye, safety of the test article, rescue of the LHON mouse model, and the
      severe irreversible loss of visual function in LHON support clinical testing with
      mutated G11778A mitochondrial DNA in our patients. 

PMID- 24457992
TI  - Assembly of nanoions via electrostatic interactions: ion-like behavior of charged
      noble metal nanoclusters.
AB  - The assembly of ultrasmall metal nanoclusters (NCs) is of interest to both basic
      and applied research as it facilitates the determination of cluster structures
      and the customization of cluster physicochemical properties. Here we present a
      facile and general approach to assemble noble metal NCs by selectively inducing
      electrostatic interactions between negatively-charged metal NCs and divalent
      cations. The charged metal NCs, which have well-defined sizes, charges and
      structures; and behave similarly to multivalent anions, can be considered as
      nanoions. These nanoions exhibit step-like assembly behavior when interacting
      with the counter cations - assembly only occurs when the solubility product (Ksp)
      between the carboxylate ions on the NC surface and the divalent cations is
      exceeded. The assembly here is distinctively different from the random
      aggregation of colloidal particles by counter ions. The nanoions would assemble
      into fractal-like monodisperse spherical particles with a high order of
      regularity that mimic the assembly of ionic crystals. 

PMID- 24457993
TI  - Prenatal exposure to alcohol and 3,4-methylenedioxymethamphetamine (ecstasy)
      alters adult hippocampal neurogenesis and causes enduring memory deficits.
AB  - Recreational drug use among pregnant women is a source of concern due to
      potential harmful effects of drug exposure on prenatal and infant development.
      The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and
      alcohol is prevalent among young adults, including young expectant mothers. Here,
      we used a rat model to study the potential risks associated with exposure to
      alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both
      alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring
      treated prenatally with the combination of alcohol and MDMA, but not those
      exposed to either drug separately, showed at 3 months of age decreased
      exploratory activity and impaired working memory function. Prenatal treatment
      with the combination of alcohol and MDMA decreased proliferation of neuronal
      precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo
      2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying
      doublecortin expression. These results provide the first evidence that the
      simultaneous abuse of alcohol and ecstasy during pregnancy, even for short
      periods of time, may cause significant abnormalities in neurocognitive
      development.

PMID- 24457994
TI  - Genetic background for development of resistance mutations within the HCV NS3
      protease-helicase in direct acting antiviral naive patients.
AB  - BACKGROUND: Subtype-specific response to ketoamide NS3 protease inhibitors is
      observed in patients with genotype 1 HCV infection. Whether the genetic diversity
      in the molecular target site of ketoamide compounds prior to treatment plays a
      role for resistance development and lower treatment response in subtype 1a is
      poorly understood. METHODS: Using a public database, we retrieved worldwide NS3
      sequence information of 581 dominant HCV variants from patients chronically
      infected with genotype 1 that were naive to direct-acting antivirals. We applied
      measures from phylogeny to study the pretreatment genetic diversity and
      complexity in NS3 full-length as well as the protease-helicase interface for
      subtype 1a and 1b, respectively. RESULTS: We found polymorphic sites more
      frequently in variants of subtype 1b than subtype 1a. Moreover, a significantly
      higher number of synonymous and non-synonymous substitutions were found in
      subtype 1b (P<0.001). Transitions were more frequent than transversions, most
      notably in subtype 1a, whereas the higher average number of nucleotide
      differences per site was found in subtype 1b. A comparison of NS3 full-length
      versus domain interface residues for both subtypes revealed a significant
      difference only for synonymous substitutions (P<0.001). CONCLUSIONS: Our study
      suggests that the nature of a mismatch nucleotide exchange in NS3 may constitute
      an important viral genetic factor for response to ketoamide protease inhibitors.
      Our analysis further suggests that the subtype-specific pace of resistance
      development seen in clinical trials is not primarily related to differences in
      genetic diversity in the direct acting antiviral naive population, but rather
      appears to correlate with the natural frequency of transition mutations
      characteristic of each subtype.

PMID- 24457995
TI  - A streamlined synthesis of extended thiophloroglucinol ligands and their
      trinuclear NiII3 complexes.
AB  - A protocol for the synthesis of trinucleating C3-symmetric ligands based on a
      central meta-phenylene bridging 1,3,5-trimercaptobenzene (thiophloroglucinol)
      backbone has been established. The key compound turned out to be the trialdehyde
      obtained from the triple nucleophilic attack of dimethyldithiocarbamate at 1,3,5
      tribromo-2,4,6-triformylbenzene. Reacting this trialdehyde with six equivalents
      of a primary amine results in the simultaneous dithiocarbamate cleavage and
      Schiff-base formation providing the extended thiophloroglucinol ligands
      H3bertdien, H6bert(Me), H6bert(t-Bu2), and H6habbi. Reaction with Ni(II) leads to
      the formation of the trinuclear Ni(II)3 complexes [(bertdien)Ni(II)3](X)3 (X =
      BPh4(-), BF4(-)), [(bert(Me))Ni(II)3], [(bert(t-Bu2))Ni(II)3], and
      [(habbi)Ni(II)3], which are characterized spectroscopically, electrochemically,
      and crystallographically. 

PMID- 24457996
TI  - Structural elucidation of two photolytic degradation products of tetrabenazine.
AB  - During solution formulation study of tetrabenazine (TBZ), a dopamine depleting
      agent, used in chorea associated with Huntington's disease and symptomatic
      treatment of hyperkinetic movement disorder it was observed a strong
      discoloration upon storage. We investigated this physico-chemical behavior by
      implementing forced degradation studies. It was observed yellowing only under
      Suntest((r)) light exposure of TBZ solution. LC-MS (liquid chromatography coupled
      to mass spectrometer detection) analysis of light exposed TBZ samples allowed us
      to propose 1,11b-dedihydrotetrabenazine (DTBZ) and 1,3,4,11b
      detetrahydrotetrabenazine (TTBZ) as the main TBZ impurities. Synthesis and
      complete structural determination of DTBZ and TTBZ.HCl by NMR and X-ray
      crystallography were carried out. They were identical in LC-MS with polar
      impurities found in light exposed TBZ samples. However, even if these TBZ
      degradation products are correlated with discoloration of TBZ solution there is
      no evidence they are directly responsible of it. 

PMID- 24457997
TI  - SLAP displays tumour suppressor functions in colorectal cancer via
      destabilization of the SRC substrate EPHA2.
AB  - The adaptor SLAP is a negative regulator of receptor signalling in immune cells
      but its role in human cancer is ill defined. Here we report that SLAP is
      abundantly expressed in healthy epithelial intestine but strongly downregulated
      in 50% of colorectal cancer. SLAP overexpression suppresses cell tumorigenicity
      and invasiveness while SLAP silencing enhances these transforming properties.
      Mechanistically, SLAP controls SRC/EPHA2/AKT signalling via destabilization of
      the SRC substrate and receptor tyrosine kinase EPHA2. This activity is
      independent from CBL but requires SLAP SH3 interaction with the ubiquitination
      factor UBE4A and SLAP SH2 interaction with pTyr594-EPHA2. SRC phosphorylates
      EPHA2 on Tyr594, thus creating a feedback loop that promotes EPHA2 destruction
      and thereby self-regulates its transforming potential. SLAP silencing enhances
      SRC oncogenicity and sensitizes colorectal tumour cells to SRC inhibitors.
      Collectively, these data establish a tumour-suppressive role for SLAP in
      colorectal cancer and a mechanism of SRC oncogenic induction through
      stabilization of its cognate substrates. 

PMID- 24457998
TI  - An alternative to the traditional cold pressor test: the cold pressor arm wrap.
AB  - Recently research on the relationship between stress and cognition, emotion, and
      behavior has greatly increased. These advances have yielded insights into
      important questions ranging from the nature of stress' influence on addiction(1)
      to the role of stress in neural changes associated with alterations in decision
      making(2,3). As topics being examined by the field evolve, however, so too must
      the methodologies involved. In this article a practical and effective alternative
      to a classic stress induction technique, the cold pressor test (CPT), is
      presented: the cold pressor arm wrap (CPAW). CPT typically involves immersion of
      a participant's dominant hand in ice-cold water for a period of time(4). The
      technique is associated with robust activation of the sympatho-adrenomedullary
      (SAM) axis (and release of catecholamines; e.g. adrenaline and noradrenaline) and
      mild-to-moderate activation of the hypothalamic-pituitary-adrenal (HPA) axis with
      associated glucocorticoid (e.g. cortisol) release. While CPT has been used in a
      wide range of studies, it can be impractical to apply in some research
      environments. For example use of water during, rather than prior to, magnetic
      resonance imaging (MRI) has the potential to damage sensitive and expensive
      equipment or interfere with acquisition of MRI signal. The CPAW is a practical
      and effective alternative to the traditional CPT. Composed of a versatile list of
      inexpensive and easily acquired components, CPAW makes use of MRI-safe gelpacs
      cooled to a temperature similar to CPT rather than actual water. Importantly CPAW
      is associated with levels of SAM and HPA activation comparable to CPT, and can
      easily be applied in a variety of research contexts. While it is important to
      maintain specific safety protocols when using the technique, these are easy to
      implement if planned for. Creation and use of the CPAW will be discussed.

PMID- 24457999
TI  - Doubling of muscle carnosine concentration does not improve laboratory 1-hr
      cycling time-trial performance.
AB  - Muscle carnosine loading through chronic oral beta-alanine supplementation has
      been shown to be effective for short-duration, high-intensity exercise. This
      randomized, placebo-controlled study explored whether the ergogenic effect of
      beta-alanine supplementation is also present for longer duration exercise.
      Subjects (27 well-trained cyclists/triathletes) were supplemented with either
      beta-alanine or placebo (6.4 g/day) for 6 weeks. Time to completion and
      physiological variables for a 1-hr cycling time-trial were compared between
      preand postsupplementation. Muscle carnosine concentration was also assessed via
      proton magnetic resonance spectroscopy before and after supplementation.
      Following beta-alanine supplementation, muscle carnosine concentration was
      increased by 143 +/- 151% (mean +/- SD; p < .001) in the gastrocnemius and 161 +/
      56% (p < .001) in the soleus. Postsupplementation time trial performance was
      significantly slower in the placebo group (60.6 +/- 4.4-63.0 +/- 5.4 min; p <
      .01) and trended toward a slower performance following beta-alanine
      supplementation (59.8 +/- 2.8-61.7 +/- 3.0 min; p = .069). We found an increase
      in lactate/proton concentration ratio following beta-alanine supplementation
      during the time-trial (209.0 +/- 44.0 (beta-alanine) vs. 161.9 +/- 54.4
      (placebo); p < .05), indicating that a similar lactate concentration was
      accompanied by a lower degree of systemic acidosis, even though this acidosis was
      quite moderate (pH ranging from 7.30 to 7.40). In conclusion, chronic beta
      alanine supplementation in well-trained cyclists had a very pronounced effect on
      muscle carnosine concentration and a moderate attenuating effect on the acidosis
      associated with lactate accumulation, yet without affecting 1-h time-trial
      performance under laboratory conditions. 

PMID- 24458000
TI  - A bispyrene derivative as a selective fluorescent probe for RNA.
AB  - A novel bispyrene compound was synthesized to selectively detect RNA through
      excimer emission "turn-on" in aqueous solution at physiological pH (7.4). The
      compound was used to successfully image RNA in HeLa cells. 

PMID- 24458001
TI  - Panax notoginseng saponins improve erectile function through attenuation of
      oxidative stress, restoration of Akt activity and protection of endothelial and
      smooth muscle cells in diabetic rats with erectile dysfunction.
AB  - Panax notoginseng saponins (PNS), which have an antioxidant property, are a
      widely used traditional Chinese medicine. In this study we investigated whether
      PNS can improve erectile function in rats with erectile dysfunction and the
      underlying mechanism by using a rat diabetic erectile dysfunction model. The rats
      were randomly divided into four groups: three PNS-treated groups (50, 100 and 150
      mg/kg) and one saline-treated control group. Four weeks post treatment,
      electrostimulation was applied to the cavernous nerve and intracavernous pressure
      was measured to assess erectile function. Malondialdehyde, superoxide dismutase
      and glutathione were detected in the penises of all rats. Ultrastructural changes
      in the penises were examined by electron microscopy. Expression of Akt was
      detected by immunohistochemistry. The results showed that intracavernous pressure
      was increased in PNS-treated groups (100 and 150 mg/kg) compared to the control
      group. The levels of superoxide dismutase, glutathione and Akt were increased (p
      < 0.05) while that of malondialdehyde was decreased in the PNS groups. Ruptured
      endothelium, impaired smooth muscle cells and thrombus in the penises were
      detected by electron microscopy in the control group, but not in the PNS groups
      (10 and 150 mg/kg). The results suggest that PNS improves erectile function in
      diabetic rats. This improvement was associated with increased Akt expression,
      suppressed oxidative stress and restored functions of endothelial cells and
      smooth muscle cells in the penis.

PMID- 24458002
TI  - Posterior minimally invasive plate osteosynthesis for humeral shaft fractures.
AB  - Fractures of the humeral shaft are common. Most of them can be successfully
      treated without surgery. In some cases, an operative intervention may offer
      faster and better functional results. One of the major problems with the open
      plating osteosynthesis is the extensive soft tissue stripping and disruption of
      periosteal circulation, caused by extensive surgical exposure, resulting in a
      relatively high rate of nonunion. Minimally invasive plate osteosynthesis (MIPO)
      techniques were developed to achieve a biologic fixation, although minimizing the
      complications of an open reduction. The incisions are small and remote from the
      fracture site to avoid direct fracture exposure. Thereby, MIPO technique obtains,
      theoretically, higher rates of union, lower infection risk, and decreases the
      need for bone graft. In the last years, MIPO has gained popularity with
      satisfactory clinical outcomes in the treatment of long bone fractures,
      especially in lower extremity. MIPO for humeral shaft fractures, however, could
      be a surgically dangerous procedure because of the risk of radial nerve injury.
      It was described by anterior and lateral approach. Humeral middle shaft fractures
      are possible to treat with a MIPO technique through an anterior, lateral, or a
      posterior approach. However, when the fracture is near the olecranon fossa,
      anterior approach is not possible as there is not enough space in the distal
      fragment to insert the amount of screws required to achieve stability. In this
      case, the posterior approach may be a good option for treatment. This article
      describes the MIPO technique through a posterior approach for the treatment of
      humeral shaft fractures. 

PMID- 24458003
TI  - Promoting health in Georgia.
AB  - This paper discusses the public health situation in Georgia. In 1991 Georgia
      became an independent republic following the collapse of the Soviet Union. The
      armed conflict with Russia in 2008 and political unrest in recent years has
      presented the Georgian population and politicians with a demanding situation. As
      part of the WHO European Region, the Commonwealth of Independent States (CIS)
      including Georgia is on the unfortunate side of a European health divide, with
      low male life expectancy and high under-five mortality. There is also a high
      degree of economic inequality in the population. We first look at the main
      players and the current strategies in public health work. Next we discuss this on
      the background of health promotion principles and recent international
      developments in knowledge and policy recommendations in the field of health
      promotion. Finally we point to some of the major public health challenges that
      Georgia faces. We conclude that the Georgian focus on reducing risk behaviours
      and improving access to quality health care is worthy of praise, but that this is
      not sufficient to solve the current public health challenges. Strategies for
      working across sectors with social determinants of health should be built into
      Georgian health thinking and policies. A health promotion work force should be
      developed. International developments such as the Commission on Social
      Determinants of Health (CSDH) report, the 'Health 2020' framework and the HP Core
      Competencies project all provide useful input to future development of healthy
      public policies in Georgia. 

PMID- 24458004
TI  - Globalization, localization and food culture: perceived roles of social and
      cultural capitals in healthy child feeding practices in Japan.
AB  - OBJECTIVES: The current study examined parental perceptions of sociocultural
      factors associated with healthy child feeding practices among parents of
      preschool-age children in rural Japan. METHODS: Fifteen Japanese mothers of
      preschool-age children participated in this qualitative study. These participants
      were aged 22-39 years and resided in a rural town in western Japan. We conducted
      semi-structured qualitative interviews to assess parental perceptions of healthy
      child feeding practices and their relationships with globalization and
      localization. These interviews were transcribed, translated into English and
      coded, based on the principles of grounded theory. A codebook was developed and
      pre-identified, and the newly-identified themes from this codebook were examined
      and compared. RESULTS: Overall, local and seasonal foods, along with traditional
      Japanese foods and simple foods (soshoku), were considered to be beneficial for
      children. Participants also noted that children were expected to be mindful and
      exhibit good table manners that reflect cultural values related to meal-time
      socializing or family bonding, and food appreciation. On the other hand, the
      majority of the participants stated that foods containing food additives and
      imported foods were unsuitable for children. Participants noted that strong
      social capital, especially social support from their mothers or mothers-in-law,
      as well as social networks for obtaining fresh local foods, contributed to
      healthy child feeding practices. Cultural capital (including the preservation of
      traditional Japanese dietary habits, eating rules and inter-generational
      commensality), was also identified as being key to healthy feeding practices.
      CONCLUSIONS: Identifying and promoting the social and cultural capital that
      positively support healthy child feeding practices may be an important component
      of nutrition education programs.

PMID- 24458005
TI  - A snapshot of global health education at North American universities.
AB  - Global health education is becoming increasingly prominent in North America. It
      is widely agreed upon that global health is an important aspect of an education
      in the health sciences and increasingly in other disciplines such as law,
      economics and political science. There is currently a paucity of studies
      examining the content of global health courses at the post-secondary level. The
      purpose of our research is to identify the content areas being covered in global
      health curricula in North American universities, as a first step in mapping
      global health curricula across North America. We collected 67 course syllabi from
      31 universities and analyzed the topics covered in the course. This snapshot of
      global health education will aid students searching for global health content, as
      well as educators and university administrators who are developing or expanding
      global health programs in Canada and the United States. 

PMID- 24458006
TI  - p2y12 receptor inhibitors in acute coronary syndromes: from the research
      laboratory to the clinic and vice versa.
AB  - The P2Y12 receptor plays a pivotal role in platelet activation and aggregation
      through a complex cascade of actions. Laboratory and clinical data have
      convincingly shown the benefit of P2Y12 inhibition combined with aspirin in
      patients with acute coronary syndrome (ACS)/undergoing percutaneous coronary
      intervention (PCI). Newer agents - like prasugrel, ticagrelor, and cangrelor -
      provide more consistent, faster, and stronger platelet inhibition than
      clopidogrel. In large clinical trials newer agents have resulted in fewer
      ischemic complications (though with increased bleeding potential) than
      clopidogrel. High-risk subpopulations like ST-segment elevation myocardial
      infarction, diabetes, chronic kidney disease, elderly, and low body weight
      patients have been identified. A 'return to the laboratory' has been observed
      recently, with several pharmacodynamic studies being performed particularly in
      these cohorts. This interplay between research laboratory and clinical data may
      lead to a more efficient and safer use of P2Y12 inhibitors.

PMID- 24458007
TI  - Dissection of autophagy in human platelets.
AB  - Continuous turnover of intracellular components by autophagy is necessary to
      preserve cellular homeostasis in all tissues. Despite recent advances in
      identifying autophagy-related genes and understanding the functions of autophagy
      in developmental and pathological conditions, so far, the role of autophagy in
      platelet, a specific anucleate cell type, is poorly understood. In this study, we
      showed that human platelets express the autophagy-related proteins ATG5, ATG7,
      and LC3. The same as in nucleated mammalian cells, autophagy was stimulated by
      cell starvation or the MTOR inhibitor rapamycin in a phosphatidylinositol 3
      kinase (PtdIns3K)-dependent manner. Disruption of autophagic flux led to
      impairment of platelet aggregation and adhesion. Furthermore, Becn1 heterozygous
      knockout mice displayed a prolonged bleeding time and reduced platelet
      aggregation. These results suggest a potential role of autophagy in the
      regulation of platelet function, and imply that gene transcription may not be an
      essential prerequisite for adaptive autophagy. 

PMID- 24458008
TI  - The integrative management of treatment-resistant depression: a comprehensive
      review and perspectives.
AB  - BACKGROUND: Major depressive disorder is a prevalent and disabling illness.
      Notwithstanding numerous advances in the pharmacological treatment of depression,
      approximately 70% of patients do not remit after first-line antidepressant
      treatment. METHODS: The MEDLINE/PubMed, EMBASE and ClinicalTrials.gov electronic
      databases were searched from inception to October 1, 2013, for randomized
      controlled trials (RCT), relevant open-label trials, meta-analyses and ongoing
      trials of pharmacological and psychotherapeutic approaches to treatment-resistant
      depression (TRD). RESULTS: Switching to a different antidepressant is a useful
      option following nonresponse to a first-line agent. Although widely used in
      clinical practice, there is limited evidence to support antidepressant
      combination for TRD. Notwithstanding evidence for lithium or T3 augmentation to
      be successful in TRD, most studies were carried out when participants were
      treated with tricyclic antidepressants (TCA). Of the available strategies to
      augment the response to new-generation antidepressants, the use of some atypical
      antipsychotics is best supported by evidence. Several novel therapeutic options
      are currently discussed. Evidence suggests that cognitive therapy (CT) is an
      effective strategy for TRD. CONCLUSIONS: The success of switching to a different
      antidepressant following a first-line agent is supported by evidence, but there
      is limited evidence for effective combination strategies. Lithium and T3
      augmentation of TCA have the strongest evidence base for successful treatment of
      TRD. The use of augmentation of newer-generation antidepressants with atypical
      antipsychotics is supported by a growing evidence base. Current evidence supports
      CT as an effective strategy for TRD. There is a need for additional large-scale
      RCT of TRD. The development of new antidepressants targeting novel pathways opens
      a promising perspective for the management of TRD.

PMID- 24458009
TI  - Micro- or nanorod and nanosphere structures derived from a series of phenyl
      porphyrins.
AB  - We examine here a series of meso-phenyl porphyrin micro- and nanostructures.
      Optical absorption and emission spectroscopy imaging and atomic force microscopy
      are used to investigate the effect of peripheral groups in nano- and
      microstructures of 5,10,15,20-tetraphenylporphyrin (H2TPP) compared to three
      other phenylporphyrins, i.e. 5,10,15-triphenylporphyrin (H2-Tri-PP), 5,10
      diphenylporphyrin (H25,10-BPP) and 5,15-diphenylporphyrin (H25,15-BPP) molecules.
      We show that nanospheres and nanorods are formed, the occurrence and properties
      of which are influenced by the number and position of the phenyl substituents. 

PMID- 24458011
TI  - Cutaneous iontophoresis of treprostinil in systemic sclerosis: a proof-of-concept
      study.
AB  - Ischemic digital ulcer (DU) is a serious complication of systemic sclerosis
      (SSc). Intravenous prostanoids are the only approved treatment for active DUs,
      but they induce dose-limiting side effects and require hospitalization. Our
      objective was to evaluate the effect of iontophoresis (a noninvasive drug
      delivery method) of treprostinil in SSc patients. Three studies were conducted: a
      pharmacokinetic study in 12 healthy volunteers showed that peak dermal
      concentration was reached at 2 hours, whereas plasma treprostinil was undetected.
      Then, a placebo-controlled, double-blind incremental dose study assessed the
      effect of treprostinil on digital skin blood flow in 22 healthy subjects. The
      effect of the highest dose was then compared with that of placebo in 12 SSc
      patients. Treprostinil significantly increased skin blood flow in healthy
      subjects (P = 0.006) and in SSc patients (P = 0.023). In conclusion, digital
      iontophoresis of treprostinil is feasible, is well tolerated, and increases
      digital skin perfusion. It could be tested as a treatment for SSc-related DUs. 

PMID- 24458012
TI  - The paradox of scientific excellence and the search for productivity in
      pharmaceutical research and development.
AB  - Scientific advances in specialty areas are proceeding at a rapid rate, but the
      research and development enterprise seems unable to take full advantage.
      Harnessing the steady stream of knowledge and inventions from different
      disciplines is the critical management issue of our time. This article suggests a
      framework for a management-directed effort to improve productivity by enhancing
      interdisciplinary collaboration. 

PMID- 24458010
TI  - Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome
      P450 2D6 genotype and codeine therapy: 2014 update.
AB  - Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic
      cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are
      governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6
      variability. We summarize evidence from the literature supporting this
      association and provide therapeutic recommendations for codeine based on CYP2D6
      genotype. This document is an update to the 2012 Clinical Pharmacogenetics
      Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine
      therapy. 

PMID- 24458013
TI  - The effects of technological advances on outcomes for elderly persons with
      exudative age-related macular degeneration.
AB  - IMPORTANCE Exudative age-related macular degeneration (ARMD) is the major cause
      of blindness among US elderly. Developing effective therapies for this disease
      has been difficult. OBJECTIVES To assess the effects of introducing new therapies
      for treating exudative ARMD on vision of the affected population and other
      outcomes among Medicare beneficiaries newly diagnosed as having ARMD. DESIGN The
      study used data from a 5% sample of Medicare claims and enrollment data with a
      combination of a regression discontinuity design and propensity score matching to
      assess the effects on the introduction or receipt of new technologies on study
      outcomes during a 2-year follow-up period. SETTING AND PARTICIPANTS The analysis
      was based on longitudinal data for the United States, January 1, 1994, to
      December 31, 2011, for Medicare beneficiaries with fee-for-service coverage. The
      sample was limited to beneficiaries 68 years or older newly diagnosed as having
      exudative ARMD as indicated by beneficiaries having no claims with this diagnosis
      in a 3-year look-back period. EXPOSURES The comparisons with vision outcomes were
      after vs before the introduction of photodynamic therapy and anti-vascular
      endothelial growth factor (VEGF) therapy. The comparisons for depression and long
      term care facility admission were between beneficiaries newly diagnosed as having
      exudative ARMD who received photodynamic therapy or anti-VEGF therapy compared
      with beneficiaries having the diagnosis who received no therapy for this disease.
      MAIN OUTCOMES AND MEASURES Onset of decrease in vision, vision loss or blindness,
      depression, and admission to a long-term care facility. RESULTS Among
      beneficiaries newly diagnosed as having exudative ARMD, the introduction of anti
      VEGF therapy reduced vision loss by 41% (95% CI, 52%-68%) and onset of severe
      vision loss and blindness by 46% (95% CI, 47%-63%). Such beneficiaries who
      received anti-VEGF therapy and were not admitted to a long-term care facility
      during the look-back period were 19% (95% CI, 72%-91%) less likely on average to
      be admitted to a long-term care facility during the follow-up period. CONCLUSIONS
      AND RELEVANCE This study demonstrates gains in population vision from the
      introduction of anti-VEGF therapy for patients 68 years or older with an
      exudative ARMD diagnosis in community-based settings in the United States. 

PMID- 24458014
TI  - Combination of cross-sectional and molecular imaging studies in the localization
      of gastroenteropancreatic neuroendocrine tumors.
AB  - Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET)
      pathophysiology for both diagnostic imaging and therapeutic purposes. The
      characteristic metabolic pathways of NET determine which tracers are useful for
      their visualization. In this review, we summarize the diagnostic value of all
      available molecular imaging studies, present data about their use in daily
      practice in NET centers globally, and finally make recommendations about the
      appropriate use of those modalities in specific clinical scenarios. Somatostatin
      receptor scintigraphy (SRS) continues to have a central role in the diagnostic
      workup of patients with NET, as it is also widely available. However, and despite
      the lack of prospective randomized studies, many NET experts predict that Gallium
      68 ((68)Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in
      the future, not only because of their technical advantages, but also because they
      are superior in patients with small-volume disease, in patients with skeletal
      metastases, and in those with occult primary tumors. Carbon-11 ((11)C)-5-hydroxy
      L-tryptophan (5-HTP) PET and (18)F-dihydroxyphenylalanine ((18)F-DOPA) PET are
      new molecular imaging techniques of limited availability, and based on
      retrospective data, their sensitivities seem to be inferior to that of (68)Ga
      DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for
      localization of the primary in benign insulinomas, but is currently available
      only in a few centers. Fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) PET was
      initially thought to be of limited value in NET, due to their usually slow
      growing nature. However, according to subsequent data, (18)F-FDG PET is
      particularly helpful for visualizing the more aggressive NET, such as poorly
      differentiated neuroendocrine carcinomas, and well-differentiated tumors with
      Ki67 values >10%. According to limited data, (18)F-FDG-avid tumor lesions, even
      in slow-growing NET, may indicate a more aggressive disease course. When a
      secondary malignancy has already been established or is strongly suspected,
      combining molecular imaging techniques (e.g. (18)F-FDG PET and (68)Ga-DOTA PET)
      takes advantage of the diverse avidities of different tumor types to
      differentiate lesions of different origins. All the above-mentioned molecular
      imaging studies should always be reviewed and interpreted in a multidisciplinary
      (tumor board) meeting in combination with the conventional cross-sectional
      imaging, as the latter remains the imaging of choice for the evaluation of
      treatment response and disease follow-up.

PMID- 24458015
TI  - Copper-catalyzed annulation of alpha-substituted diazoacetates with 2
      ethynylanilines: the direct synthesis of C2-functionalized indoles.
AB  - Copper-catalyzed direct annulation of alpha-substituted diazoacetates with 2
      ethynylanilines leading to C2-functionalized indoles was achieved under mild
      reaction conditions. The C2-(carboxylate methyl) substituted indoles were
      obtained in moderate to high yields. In addition, this procedure tolerates a
      series of N-substituted and free substituted 2-ethynylanilines. 

PMID- 24458016
TI  - Impact of academic affiliation and training on knowledge of hereditary colorectal
      cancer.
AB  - BACKGROUND: Knowledge about hereditary colorectal cancer (CRC) can aid cancer
      screening and prevention in high-risk patients. Genetic testing, once conducted
      primarily at academic centers, is now routinely performed in a variety of
      clinics. Nonacademic physicians may not be aware of hereditary CRC standards of
      care. METHODS: From August to November 2012, a survey was administered to
      predominantly primary care physicians evaluating academic center affiliation,
      past training in genetics and knowledge regarding hereditary CRC. RESULTS: One
      hundred forty physicians completed the survey. Knowledge of hereditary CRC was
      neither associated with academic affiliation nor with training during medical
      school or residency, but with continuing medical education (CME) training. Those
      with CME training were more likely to know that screening could be enhanced for
      patients with a hereditary cancer risk (OR = 4.49, 95% CI = 1.40-14.38) and that
      an individual with hereditary CRC would have different screening recommendations
      (OR = 7.49, 95% CI = 1.37-40.81). Residency training and CME training were
      associated with more frequent hereditary risk assessment. CONCLUSION: Genetics
      training may be associated with physicians' knowledge and assessment of
      hereditary CRC. Training at the CME level in particular may be integral to the
      delivery of genetic services in clinical practice.

PMID- 24458017
TI  - Ligand-based molecular recognition and dioxygen splitting: an endo epoxide
      ending.
AB  - The phosphido complex RuCp*(PPh2CH=CHPPh2)(PPh2) (1) was exposed to a number of
      small molecules and was found to recognize and activate molecular oxygen in an
      unprecedented fashion: the ruthenium species split O2 in a ligand-based 4
      electron reduction to produce an endo epoxide, as well as a phosphinito ligand.
      Based on XRD data, VT NMR studies, cyclooctene trapping studies, and crossover
      experiments it was determined that the reaction proceeded through an
      intramolecular mechanism in which initial oxidation of the phosphido ligand
      generated an end-on peroxo intermediate. This mechanism was also supported by
      computational studies and electrochemical experiments. In contrast, an analogue
      of 1, RuCp*(Ph2P(ortho-C6H4)PPh2)(PPh2) (3), reacted in an intermolecular fashion
      to generate two phosphinito ligands.

PMID- 24458018
TI  - Characterization of a setup to test the impact of high-amplitude pressure waves
      on living cells.
AB  - The impact of pressure waves on cells may provide several possible applications
      in biology and medicine including the direct killing of tumors, drug delivery or
      gene transfection. In this study we characterize the physical properties of
      mechanical pressure waves generated by a nanosecond laser pulse in a setup with
      well-defined cell culture conditions. To systematically characterize the system
      on the relevant length and time scales (micrometers and nanoseconds) we use
      photon Doppler velocimetry (PDV) and obtain velocity profiles of the cell culture
      vessel at the passage of the pressure wave. These profiles serve as input for
      numerical pressure wave simulations that help to further quantify the pressure
      conditions on the cellular length scale. On the biological level we demonstrate
      killing of glioblastoma cells and quantify experimentally the pressure threshold
      for cell destruction. 

PMID- 24458019
TI  - Paricalcitol treatment of secondary hyperparathyroidism in hemodialysis patients:
      a German-Austrian, single-arm, open-label, prospective, noninterventional,
      observational study.
AB  - BACKGROUND: Safety and efficacy of paricalcitol in hemodialysis patients with
      secondary hyperparathyroidism (sHPT) was investigated under routine clinical
      practice in German and Austrian dialysis centers. METHODS: Hemodialysis patients
      with sHPT initiating intravenous paricalcitol were enrolled in this
      noninterventional study regardless of concomitant sHPT treatment. Prior active
      vitamin D therapy was discontinued. Clinical laboratory values, including intact
      parathyroid hormone (iPTH), total serum calcium (Ca), phosphorus (P), Ca * P
      product, and alkaline phosphatase (AP), were recorded for 6 months following
      initiation of paricalcitol treatment. RESULTS: 1,313 patients (Austria, n = 280;
      Germany, n = 1,033) from 169 dialysis centers were enrolled. Most patients (n =
      932; 79.1%) had received dialysis for >=1 year. Median iPTH fell from 518.9 pg/ml
      [55.0 pmol/l] at baseline to 264.0 pg/ml [28.0 pmol/l] after 6 months (p <
      0.0001). After 6 months of treatment, >=30 and >=60% reductions in iPTH were
      observed in 63.0 and 35.9% of patients, respectively. At 6 months, 27.2% of
      patients achieved iPTH levels between 150 and <300 pg/ml [15.9 and <31.8 pmol/l]
      compared with 9.7% at baseline. Ca, P, and Ca * P levels remained stable in the
      majority of patients. AP levels declined from a median of 98 U/l at baseline to
      83 U/l (p < 0.0001) at 6 months. Monitoring of adverse events and clinical
      laboratory assessments identified no unexpected safety signals for paricalcitol.
      CONCLUSIONS: Paricalcitol is an effective and well-tolerated treatment option for
      the control of iPTH levels in hemodialysis patients with sHPT. The results of
      this study support the results of previous trials under real-time clinical
      practice conditions in Austria and Germany.

PMID- 24458020
TI  - Testing safety of germinated rye sourdough in a celiac disease model based on the
      adoptive transfer of prolamin-primed memory T cells into lymphopenic mice.
AB  - The current treatment for celiac disease is strict gluten-free diet. Technical
      processing may render gluten-containing foods safe for consumption by celiac
      patients, but so far in vivo safety testing can only be performed on patients. We
      modified a celiac disease mouse model to test antigenicity and inflammatory
      effects of germinated rye sourdough, a food product characterized by extensive
      prolamin hydrolysis. Lymphopenic Rag1-/- or nude mice were injected with splenic
      CD4+CD62L-CD44high-memory T cells from gliadin- or secalin-immunized wild-type
      donor mice. We found that: 1) Rag1-/- recipients challenged with wheat or rye
      gluten lost more body weight and developed more severe histological duodenitis
      than mice on gluten-free diet. This correlated with increased secretion of
      IFNgamma, IL-2, and IL-17 by secalin-restimulated splenocytes. 2) In vitro gluten
      testing using competitive R5 ELISA demonstrated extensive degradation of the
      gluten R5 epitope in germinated rye sourdough. 3) However, in nude recipients
      challenged with germinated rye sourdough (vs. native rye sourdough), serum anti
      secalin IgG/CD4+ T helper 1-associated IgG2c titers were only reduced, but not
      eliminated. In addition, there were no reductions in body weight loss,
      histological duodenitis, or T cell cytokine secretion in Rag1-/- recipients
      challenged accordingly. IN CONCLUSION: 1) prolamin-primed CD4+CD62L-CD44high
      memory T cells induce gluten-sensitive enteropathy in Rag1-/- mice. 2) Hydrolysis
      of secalins in germinated rye sourdough remains incomplete. Secalin peptides
      retain B and T cell stimulatory capacity and remain harmful to the intestinal
      mucosa in this celiac disease model. 3) Current antibody-based prolamin detection
      methods may fail to detect antigenic gluten fragments in processed cereal food
      products.

PMID- 24458021
TI  - Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of
      inflammatory mediators or by lung inflammation.
AB  - Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and
      fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury
      and impaired gut development. We tested whether this detrimental inflammatory
      response of the fetal gut results from a direct local (gut derived) or an
      indirect inflammatory response mediated by the chorioamnion/skin or lung, since
      these organs are also in direct contact with the amniotic fluid. The
      gastrointestinal tract was isolated from the respiratory tract and the
      amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide
      (LPS) or saline (controls) was selectively infused in the gastrointestinal tract,
      trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124
      days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure
      caused distinct inflammatory responses in the fetal gut. Inflammatory responses
      could be distinguished by the influx of leukocytes (MPO(+), CD3(+), and FoxP3(+)
      cells), tumor necrosis factor-alpha, and interferon-gamma expression and
      differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6.
      Fetal gut inflammation after direct intestinal LPS exposure resulted in severe
      loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and
      increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut
      after selective LPS instillation in the lungs caused only mild disruption of ZO
      1, loss in epithelial cell integrity, and impaired epithelial differentiation.
      LPS exposure of the amnion/skin epithelia did not result in gut inflammation or
      morphological, structural, and functional changes. Our results indicate that the
      detrimental consequences of chorioamnionitis on fetal gut development are the
      combined result of local gut and lung-mediated inflammatory responses. 

PMID- 24458022
TI  - Purse-string morphology of external anal sphincter revealed by novel imaging
      techniques.
AB  - The external anal sphincter (EAS) may be injured in 25-35% of women during the
      first and subsequent vaginal childbirths and is likely the most common cause of
      anal incontinence. Since its first description almost 300 years ago, the EAS was
      believed to be a circular or a "donut-shaped" structure. Using three-dimensional
      transperineal ultrasound imaging, MRI, diffusion tensor imaging, and muscle fiber
      tracking, we delineated various components of the EAS and their muscle fiber
      directions. These novel imaging techniques suggest "purse-string" morphology,
      with "EAS muscles" crossing contralaterally in the perineal body to the
      contralateral transverse perineal (TP) and bulbospongiosus (BS) muscles, thus
      attaching the EAS to the pubic rami. Spin-tag MRI demonstrated purse-string
      action of the EAS muscle. Electromyography of TP/BS and EAS muscles revealed
      their simultaneous contraction and relaxation. Lidocaine injection into the TP/BS
      muscle significantly reduced anal canal pressure. These studies support purse
      string morphology of the EAS to constrict/close the anal canal opening. Our
      findings have implications for the effect of episiotomy on anal closure function
      and the currently used surgical technique (overlapping sphincteroplasty) for EAS
      reconstructive surgery to treat anal incontinence. 

PMID- 24458023
TI  - Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.
AB  - Variations in the serine protease 1 (PRSS1) gene encoding human cationic
      trypsinogen have been conclusively associated with autosomal dominant hereditary
      pancreatitis and sporadic nonalcoholic chronic pancreatitis. Most high-penetrance
      PRSS1 variants increase intrapancreatic trypsin activity by stimulating
      trypsinogen autoactivation and/or by inhibiting chymotrypsin C-dependent
      trypsinogen degradation. Alternatively, some PRSS1 variants can cause trypsinogen
      misfolding, which results in intracellular retention and degradation with
      consequent endoplasmic reticulum stress. However, not all PRSS1 variants are
      pathogenic, and clinical relevance of rare variants is often difficult to
      ascertain. Here we review the PRSS1 variants published since 1996 and discuss
      their functional properties and role in chronic pancreatitis. 

PMID- 24458024
TI  - Glial cell line-derived neurotrophic factor protects against high-fat diet
      induced obesity.
AB  - Obesity is a growing epidemic with limited effective treatments. The neurotrophic
      factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to
      enhance beta-cell mass and improve glucose control in rodents. Its role in
      obesity is, however, not well characterized. In this study, we investigated the
      ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF
      transgenic (Tg) mice that overexpress GDNF under the control of the glial
      fibrillary acidic protein promoter and wild-type (WT) littermates were maintained
      on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure,
      and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and
      3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice
      resisted the HFD-induced weight gain, insulin resistance, dyslipidemia,
      hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food
      intake and activity levels. They exhibited significantly (P<0.001) higher energy
      expenditure than WT mice and increased expression in skeletal muscle and brown
      adipose tissue of peroxisome proliferator activated receptor-alpha and beta1- and
      beta3-adrenergic receptor genes, which are associated with increased lipolysis
      and enhanced lipid beta-oxidation. In vitro, GDNF enhanced beta-adrenergic
      mediated cAMP release in brown adipocytes and suppressed lipid accumulation in
      differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies
      demonstrate a novel role for GDNF in the regulation of high-fat diet-induced
      obesity through increased energy expenditure. They show that GDNF and its
      receptor agonists may be potential targets for the treatment or prevention of
      obesity.

PMID- 24458025
TI  - Evaluation of protective efficacy of the synthetic peptide vaccine containing the
      T-helper 1 epitope with CpG oligodeoxynucleotide against feline infectious
      peritonitis virus infection in cats.
AB  - BACKGROUND: Feline infectious peritonitis (FIP) is a feline coronavirus-induced
      fatal disease in domestic and wild cats. Cellular immunity is considered to play
      an important role in the prevention of FIP. Thus, induction of the cellular
      immune response is essential in vaccines against FIP virus (FIPV) infection.
      METHODS: We immunized cats with peptides containing T-helper (Th)1 epitopes
      derived from the nucleocapsid (N) protein of the type I FIPV KU-2 strain (NP7 and
      NP8) with feline CpG-oligodeoxynucleotides (fCpG-ODNs) as a vaccine adjuvant.
      RESULTS: Prevention against type II FIPV 79-1146 strain-induced FIP was slightly
      better in specific pathogen-free cats treated with NP7 and NP8 with fCpG-ODNs.
      However, immune tolerance was suggested to be induced by the high dose and
      frequency of NP7 and NP8 with fCpG-ODNs. CONCLUSIONS: Further investigations on
      the combination and concentrations of the peptides and fCpG-ODNs, dose, frequency
      and route of administration are needed.

PMID- 24458026
TI  - [Orthopaedic implants. Application outside of patient care?].
AB  - Internal fracture fixation represents a widespread concept for the treatment of
      fractures. As the number of implants increases, person tracking may be possible.
      In spring 2010 near Rostock (Germany), human remains including a stainless steel
      nail were found. Forensic analysis considered the parts of skeleton to belong to
      a man of medium height, exposed to outdoor conditions for several years to a few
      decades. The tibial nail was analysed and according to the product identification
      number possible hospitals of implant placement and transportation paths were
      determined and screened. Furthermore a match analysis of the database of missing
      individuals of the last 15 years was undertaken and a DNA match analysis
      identified a local individual who had been missing since winter 2003. Equipped
      with the actual patient's identity, out of academic interest a survey of clinical
      documents such as discharge letters and operative reports was performed, but was
      inconclusive. Although technically feasible, tracking the patient in this case
      based on the implant product number itself was unsuccessful. In this case report,
      the feasibility, validity and efficiency of this option are presented and
      discussed. 

PMID- 24458027
TI  - A role for sorting nexin 27 in AMPA receptor trafficking.
AB  - Sorting nexin 27 (SNX27), a PDZ domain-containing endosomal protein, was recently
      shown to modulate glutamate receptor recycling in Down's syndrome. However, the
      precise molecular role of SNX27 in GluA1 trafficking is unclear. Here we report
      that SNX27 is enriched in dendrites and spines, along with recycling endosomes.
      Significantly, the mobilization of SNX27 along with recycling endosomes into
      spines was observed. Mechanistically, SNX27 interacts with K-ras GTPase via the
      RA domain; and following chemical LTP stimuli, K-ras is recruited to SNX27
      enriched endosomes through a Ca(2+)/CaM-dependent mechanism, which in turn drives
      the synaptic delivery of homomeric GluA1 receptors. Impairment of SNX27 prevents
      LTP and associated trafficking of AMPARs. These results demonstrate a role for
      SNX27 in neuronal plasticity, provide a molecular explanation for the K-ras
      signal during LTP and identify SNX27 as the PDZ-containing molecular linker that
      couples the plasticity stimuli to the delivery of postsynaptic cargo. 

PMID- 24458028
TI  - Ultrasonic assessment of myocardial microstructure.
AB  - Echocardiography is a widely accessible imaging modality that is commonly used to
      noninvasively characterize and quantify changes in cardiac structure and
      function. Ultrasonic assessments of cardiac tissue can include analyses of
      backscatter signal intensity within a given region of interest. Previously
      established techniques have relied predominantly on the integrated or mean value
      of backscatter signal intensities, which may be susceptible to variability from
      aliased data from low frame rates and time delays for algorithms based on cyclic
      variation. Herein, we describe an ultrasound-based imaging algorithm that extends
      from previous methods, can be applied to a single image frame and accounts for
      the full distribution of signal intensity values derived from a given myocardial
      sample. When applied to representative mouse and human imaging data, the
      algorithm distinguishes between subjects with and without exposure to chronic
      afterload resistance. The algorithm offers an enhanced surrogate measure of
      myocardial microstructure and can be performed using open-access image analysis
      software.

PMID- 24458029
TI  - Successful endourological management of the 'forgotten' stent in a transplanted
      kidney.
AB  - BACKGROUND: Ureteric stents are used to prevent urological complications like
      ureteric fistulas and obstruction in kidney transplants. Despite its advantages,
      complications arising from delayed removal of a double J (DJ) stent include
      urinary tract infections, stone encrustation, and migration of the DJ stent
      [Sansalone et al.: Transplant Proc 2005;37:2511-2515]. Encrustation of the stent
      makes removal difficult and risks injury to the transplanted kidney. CASE
      PRESENTATION: We report a case of retained DJ stent for 19 years presenting with
      recurrent urinary tract infections. A radiograph revealed a retained ureteric
      stent extending from the right iliac fossa transplant kidney to the urinary
      bladder with multiple foci of large calcification along its length. Two sessions
      of extracorporeal shockwave lithotripsy along the stent were performed after a
      percutaneous nephrostomy tube had been placed in the transplanted kidney.
      Subsequently, the retained DJ stent was removed endoscopically after laser
      lithotripsy to remnant calcifications. Remnant stone fragments were removed with
      another session of ureteroscopy and laser lithotripsy. The patient achieved
      complete stent and stone clearance with a functioning graft. CONCLUSION: This
      case illustrates that significant stone encrustation of the retained stent in a
      transplanted kidney can be treated successfully with a combination of
      endourological techniques.

PMID- 24458030
TI  - Inverse and direct cancer comorbidity in people with central nervous system
      disorders: a meta-analysis of cancer incidence in 577,013 participants of 50
      observational studies.
AB  - BACKGROUND: There is a lack of scientific consensus about cancer comorbidity in
      people with central nervous system (CNS) disorders. This study assesses the co
      occurrence of cancers in patients with CNS disorders, including Alzheimer's
      disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders,
      Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS),
      Parkinson's disease (PD) and schizophrenia (SCZ). METHOD: Comprehensive search in
      PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published
      before March 2013. We identified 51 relevant articles from 2,229 discrete
      references, 50 of which contained data suitable for quantitative synthesis
      (577,013 participants). Pooled effect sizes (ES) were calculated using multiple
      random-effects meta-analyses. Sources of heterogeneity and uncertainty were
      explored by means of subgroup and sensitivity analyses, respectively. RESULTS:
      The presence of CNS disorders was associated with a reduced co-occurrence of
      cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I(2) = 94.5%). A
      consistently lower overall co-occurrence of cancer was detected in patients with
      neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I(2) = 82.8%), and in
      those with AD (ES = 0.32; 95% CI: 0.22-0.46; I(2) = 0.0%), PD (ES = 0.83; 95% CI:
      0.76-0.91; I(2) = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I(2) = 30.3%) and HD
      (ES = 0.53; 95% CI: 0.42-0.67; I(2) = 56.4%). Patients with DS had a higher
      overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I(2) = 87.9%). No
      association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25;
      I(2) = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I(2) = 96.3%). Patients with
      PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD
      with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower
      co-occurrence of other specific cancers (e.g. lung, prostate and colorectal
      cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer
      in SCZ). CONCLUSION: Increased and decreased co-occurrence of cancer in patients
      with CNS disorders represents an opportunity to discover biological and non
      biological connections between these complex disorders.

PMID- 24458031
TI  - Fibrinogen and platelet contributions to clot formation: implications for trauma
      resuscitation and thromboprophylaxis.
AB  - BACKGROUND: Thromboelastography (TEG) is used to diagnose perturbations in clot
      formation and lysis that are characteristic of acute traumatic coagulopathy. With
      novel functional fibrinogen (FF) TEG, fibrin- and platelet-based contributions to
      clot formation can be elucidated to tailor resuscitation and thromboprophylaxis.
      We sought to describe the longitudinal contributions of fibrinogen and platelets
      to clot strength after injury, hypothesizing that low levels of FF and a low
      contribution of fibrinogen to clot strength on admission would be associated with
      coagulopathy, increased transfusion requirements, and worse outcomes. METHODS: A
      total of 603 longitudinal plasma samples were prospectively collected from 251
      critically injured patients at a single Level 1 trauma center from 0 hour to 120
      hours. TEG maximal amplitude (MA), FF MA, FF levels, von Clauss fibrinogen, and
      standard coagulation measures were performed in parallel. Percentage
      contributions of FF (%MA(FF)) and platelets (%MA(platelets)) were calculated as
      each MA divided by overall kaolin TEG MA. RESULTS: Coagulopathic patients
      (international normalized ratio >= 1.3) had significantly lower admission %MA(FF)
      than noncoagulopathic patients (24.7% vs. 31.2%, p < 0.05). Patients requiring
      plasma transfusion had a significantly lower admission %MA(FF) (26.6% vs. 30.6%,
      p < 0.05). Higher admission %MA(FF) was predictive of reduced mortality (hazard
      ratio, 0.815, p < 0.001). %MA(platelets) was higher than %MA(FF) at all time
      points, decreased over time, and stabilized at 72 hours (69.4% at 0 hour, 56.2%
      at 72 hours). In contrast, %MA(FF) increased over time and stabilized at 72 hours
      (30.6% at 0 hour, 43.8% at 72 hours). CONCLUSION: FF TEG affords differentiation
      of fibrin- versus platelet-based clot dynamics. Coagulopathy and plasma
      transfusion were associated with a lower %MA(FF). Despite this importance of
      fibrinogen, platelets had a greater contribution to clot strength at all time
      points after injury. This suggests that attention to these relative contributions
      should guide resuscitation and thromboprophylaxis and that antiplatelet therapy
      may be of underrecognized importance to thromboprophylaxis after trauma. LEVEL OF
      EVIDENCE: Prognostic study, level III.

PMID- 24458032
TI  - Comparison of the hemostatic efficacy of low-volume lyophilized plasma
      reconstituted using sterile water, lactated Ringer's, normal saline, and Hextend
      solutions.
AB  - BACKGROUND: Low-volume ascorbic acid-buffered reconstituted lyophilized plasma
      (LP) provides logistic advantages, reduces the risks for large-volume
      resuscitation, modulates inflammation, and is equally effective for hemostatic
      resuscitation as full-volume LP. We compared the physiologic effects of
      resuscitation using LP reconstituted with sterile water (LP-SW), lactated
      Ringer's solution (LP-LR), normal saline (LP-NS), and Hextend (LP-Hx). METHODS:
      Plasma was collected from swine, lyophilized, and then reconstituted into four
      test solutions: LP-SW, LP-LR, LP-NS, or LP-Hx. Forty swine were anesthetized and
      subjected to a validated model of polytrauma and hemorrhagic shock (including a
      Grade V liver injury), then randomized to receive one of the four test solutions.
      Physiologic parameters, blood loss, lactate, and hematocrit were followed up.
      Coagulation status was evaluated using thrombelastography. Inflammatory mediator
      expression was evaluated by multiplex serum assay. RESULTS: Forty animals were
      included in the study (10 animals per group). One animal died following LP-Hx
      resuscitation. There was less blood loss in the LP-SW and LP-LR groups compared
      with the LP-NS and LP-Hx groups (p < 0.05). The LP-SW group exhibited less early
      coagulopathic changes by thrombelastography, and the LP-Hx group had persistently
      elevated international normalized ratios at the end of the study period (p <
      0.05). Serum interleukin 6 was lower after 4 hours in the LP-SW group compared
      with LP-NS (p < 0.05). CONCLUSION: Resuscitation using low-volume LP-SW and LP-LR
      buffered with ascorbic acid confers an anti-inflammatory benefit and results in
      less blood loss. Sterile water is a safe, cost-effective, and universally
      available fluid for creating a low-volume hemostatic LP resuscitation solution.

PMID- 24458033
TI  - Age-associated impact on presentation and outcome for penetrating thoracic trauma
      in the adult and pediatric patient populations.
AB  - BACKGROUND: Studies reporting on penetrating thoracic trauma in the pediatric
      population have been limited by small numbers and implied differences with the
      adult population. Our objectives were to report on a large cohort of pediatric
      patients presenting with penetrating thoracic trauma and to determine age-related
      impacts on management and outcome through comparison with an adult cohort.
      METHODS: A Level I trauma center registry was queried between 2006 and 2012. All
      patients presenting with penetrating thoracic trauma were identified. Patient
      demographics, injury mechanism, injury severity, admission physiology, and
      outcome were recorded. Patients were compared, and outcomes were analyzed based
      on age at presentation, with patients 17 years or younger defining our pediatric
      cohort. RESULTS: A total of 1,423 patients with penetrating thoracic trauma were
      admitted during the study period. Two hundred twenty patients (15.5%) were
      pediatric, with 205 being adolescents (13-17 years) and 15 being children (<= 12
      years). In terms of management for the pediatric population, tube thoracostomy
      alone was needed in 32.7% (72 of 220), whereas operative thoracic exploration was
      performed in 20.0% (44 of 220). Overall mortality was 13.6% (30 of 220). There
      was no significant difference between the pediatric and adult population with
      regard to injury mechanism or severity, need for therapeutic intervention,
      operative approach, use of emergency department thoracotomy, or outcome. Stepwise
      logistic regression failed to identify age as a predictor for the need for either
      therapeutic intervention or mortality between the two age groups as a whole.
      However, subgroup analysis revealed that being 12 years or younger (odds ratio,
      3.84; 95% confidence interval, 1.29-11.4) was an independent predictor of
      mortality. CONCLUSION: Management of traumatic penetrating thoracic injuries in
      terms of the need for therapeutic intervention and operative approach was similar
      between the adult and pediatric populations. Mortality from penetrating thoracic
      trauma can be predicted based on injury severity, the use of emergency department
      thoracotomy, and admission physiology for adolescents and adults. Children may be
      at increased risk for poor outcome independent of injury severity. LEVEL OF
      EVIDENCE: Epidemiologic study, level III.

PMID- 24458034
TI  - Blunt cerebrovascular injury screening with 64-channel multidetector computed
      tomography: more slices finally cut it.
AB  - BACKGROUND: Aggressive screening to diagnose blunt cerebrovascular injury (BCVI)
      results in early treatment, leading to improved outcomes and reduced stroke
      rates. While computed tomographic angiography (CTA) has been widely adopted for
      BCVI screening, evidence of its diagnostic sensitivity is marginal. Previous work
      from our institution using 32-channel multidetector CTA in 684 patients
      demonstrated an inadequate sensitivity of 51% (Ann Surg. 2011,253: 444-450).
      Digital subtraction angiography (DSA) continues to be the reference standard of
      diagnosis but has significant drawbacks of invasiveness and resource demands.
      There have been continued advances in CT technology, and this is the first report
      of an extensive experience with 64-channel multidetector CTA. METHODS: Patients
      screened for BCVI using CTA and DSA (reference) at a Level 1 trauma center during
      the 12-month period ending in May 2012 were identified. Results of CTA and DSA,
      complications, and strokes were retrospectively reviewed and compared. RESULTS: A
      total of 594 patients met criteria for BCVI screening and underwent both CTA and
      DSA. One hundred twenty-eight patients (22% of those screened) had 163 injured
      vessels: 99 (61%) carotid artery injuries and 64 (39%) vertebral artery injuries.
      Sixty-four-channel CTA demonstrated an overall sensitivity per vessel of 68% and
      specificity of 92%. The 52 false-negative findings on CTA were composed of 34
      carotid artery injuries and 18 vertebral artery injuries; 32 (62%) were Grade I
      injuries. Overall, positive predictive value was 36.2%, and negative predictive
      value was 97.5%. Six procedure-related complications (1%) occurred with DSA,
      including two iatrogenic dissections and one stroke. CONCLUSION: Sixty-four
      channel CTA demonstrated a significantly improved sensitivity of 68% versus the
      51% previously reported for the 32-channel CTA (p = 0.0075). Sixty-two percent of
      the false-negative findings occurred with low-grade injuries. Considering
      complications, cost, and resource demand associated with DSA, this study suggests
      that 64-channel CTA may replace DSA as the primary screening tool for BCVI. LEVEL
      OF EVIDENCE: Diagnostic study, level III.

PMID- 24458035
TI  - Successful placement of intracranial pressure monitors by trauma surgeons.
AB  - BACKGROUND: The Brain Trauma Foundation guidelines advocate for the use of
      intracranial pressure (ICP) monitoring following traumatic brain injury (TBI) in
      patients with a Glasgow Coma Scale (GCS) score of 8 or less and an abnormal
      computed tomographic scan finding. The absence of 24-hour in-house neurosurgery
      coverage can negatively impact timely monitor placement. We reviewed the safety
      profile of ICP monitor placement by trauma surgeons trained and credentialed in
      their insertion by neurosurgeons. METHODS: In 2005, the in-house trauma surgeons
      at a Level I trauma center were trained and credentialed in the placement of ICP
      parenchymal monitors by the neurosurgeons. We abstracted all TBI patients who had
      ICP monitors placed during a 6-year period. Demographic information, Injury
      Severity Score (ISS), outcome, and monitor placement by neurosurgery or trauma
      surgery were identified. Misplacement, hemorrhage, infections, malfunctions, and
      dislodgement were considered complications. Comparisons were performed by chi
      testing and Student's t tests. RESULTS: During the 6-year period, 410 ICP
      monitors were placed for TBI. The mean (SD) patient age was 40.9 (18.9) years,
      73.7% were male, mean (SD) ISS was 28.3 (9.4), mean (SD) length of stay was 19
      (16) days, and mortality was 36.1%. Motor vehicle collisions and falls were the
      most common mechanisms of injury (35.2% and 28.7%, respectively). The trauma
      surgeons placed 71.7 % of the ICP monitors and neurosurgeons for the remainder.
      The neurosurgeons placed most of their ICP monitors (71.8%) in the operating room
      during craniotomy. The overall complication rate was 2.4%. There was no
      significant difference in complications between the trauma surgeons and
      neurosurgeons (3% vs. 0.8%, p = 0.2951). CONCLUSION: After appropriate training,
      ICP monitors can be safely placed by trauma surgeons with minimal adverse
      effects. With current and expected specialty shortages, acute care surgeons can
      successfully adopt procedures such as ICP monitor placement with minimal
      complications. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

PMID- 24458036
TI  - Routine repeat brain computed tomography in all children with mild traumatic
      brain injury may result in unnecessary radiation exposure.
AB  - BACKGROUND: Computed tomography (CT) for pediatric traumatic brain injury (TBI)
      is common. Evidence suggests that 1 in 1,200 children undergoing CT will die of
      malignancy from radiation exposure. Presently, there is no protocol for surveying
      children with mild TBI; repeat CT (rCT) is often performed. We hypothesized that
      rCT could be avoided. Outcomes of similar patients who underwent rCT were
      compared with those of patients followed by clinical examination alone. METHODS:
      An 8-year retrospective review was performed of patients admitted to a Level I
      pediatric trauma center with TBI, CT evidence of TBI, and Glasgow Coma Scale
      (GCS) score of 14 to 15. There were two groups, those who underwent rCT (rCT+)
      and those who did not (rCT-). Data included age, Injury Severity Score (ISS),
      mechanism of injury, type of TBI, and outcome. Patients with coagulopathies,
      ventriculoperitoneal shunts, developmental disabilities, nonaccidental trauma,
      concomitant injuries, or medical problems resulting in intubation or sedation not
      attributed to TBI were excluded. RESULTS: Of 391 patients admitted with TBI, 120
      were included in the study. A total of 106 patients were rCT+, and 14 were rCT-.
      rCT+ children were older (mean, 98.7 +/- 7.3 vs. 35.3 +/- 11.5 months; p =
      0.0025) and more likely to have epidural hematoma (EDH) (100% rCT with EDH vs.
      76% rCT all other TBI, p = 0.044). Mechanism of injury and mean ISS (15.2 +/- 0.6
      vs. 13.0 +/- 1.1, p = 0.195) were not different between the groups. There were no
      worsening neurologic symptoms or need for surgery in rCT- children. rCT
      identified seven patients (6.6%) with CT progression of their injury. Five had an
      EDH, and two had a subarachnoid hemorrhage. Two children with EDH underwent
      operation. CONCLUSION: Our study indicates that routine rCT without evidence of
      clinical deterioration is not indicated in children with admission GCS score of
      14 to 15 and TBI on CT scan. Children with EDH seem to have a higher potential
      for progression, and rCT seems to be indicated in this subgroup. LEVEL OF
      EVIDENCE: Therapeutic study, level IV.

PMID- 24458037
TI  - Enteral albuterol decreases the need for chronotropic agents in patients with
      cervical spinal cord injury-induced bradycardia.
AB  - BACKGROUND: Cervical spinal cord injury (CSCI) is often complicated by autonomic
      instability and life-threatening bradycardia. beta-adrenergic receptors offer a
      potential target for modulating cardiac vagal activity and heart rate. Enteral
      albuterol may mitigate symptomatic bradycardia in CSCI patients. The purpose of
      this study was to examine the effect of enteral albuterol on the frequency of
      symptomatic bradycardia and the need for rescue therapy in CSCI patients.
      METHODS: The charts of CSCI patients admitted to a Level I trauma center from
      February 2008 through March 2012 were reviewed for demographics, episodes of
      symptomatic bradycardia (defined as heart rate < 60 beats per minute and systolic
      blood pressure < 90 mm Hg), use of enteral albuterol, hospital days requiring
      chronotropic use, and total atropine administered. In the albuterol group,
      patients received scheduled enteral albuterol after experiencing symptomatic
      bradycardia, with chronotropic agents used as needed for rescue treatment. In the
      no-albuterol group, only chronotropic agents were used as needed for rescue
      treatment. The albuterol and no-albuterol groups were compared using independent
      samples Kruskal-Wallis test for total number of bradycardic episodes, hospital
      days requiring chronotropic use, and total atropine administered. RESULTS:
      Eighteen patients with CSCI-induced bradycardia were identified. Eight patients
      received treatment with enteral albuterol, and 10 patients did not. The median
      age did not differ significantly between the two groups. However, the median
      Injury Severity Score (ISS) was higher in the albuterol group (median ISS, 36.5;
      interquartile range, 35-66.5 vs. median ISS 26; interquartile range, 27-37.25 in
      no-albuterol group). Patients receiving albuterol experienced 1.8 symptomatic
      bradycardic episodes versus 4.3 episodes in those patients not receiving
      albuterol (p = 0.08). Hospital days on chronotropic agents were significantly
      less in the albuterol group (1.8 vs. 8.6, p = 0.01). One patient, in the no
      albuterol group, required pacemaker placement. CONCLUSION: Enteral albuterol may
      reduce the frequency of symptomatic bradycardia in patients with CSCI, resulting
      in less rescue therapy using chronotropic agents. LEVEL OF EVIDENCE: Therapeutic
      study, level IV.

PMID- 24458038
TI  - Multicenter review of diaphragm pacing in spinal cord injury: successful not only
      in weaning from ventilators but also in bridging to independent respiration.
AB  - BACKGROUND: Ventilator-dependent spinal cord-injured (SCI) patients require
      significant resources related to ventilator dependence. Diaphragm pacing (DP) has
      been shown to successfully replace mechanical ventilators for chronic ventilator
      dependent tetraplegics. Early use of DP following SCI has not been described.
      Here, we report our multicenter review experience with the use of DP in the
      initial hospitalization after SCI. METHODS: Under institutional review board
      approval for humanitarian use device, we retrospectively reviewed our multicenter
      nonrandomized interventional protocol of laparoscopic diaphragm motor point
      mapping with electrode implantation and subsequent diaphragm conditioning and
      ventilator weaning. RESULTS: Twenty-nine patients with an average age of 31 years
      (range, 17-65 years) with only two females were identified. Mechanism of injury
      included motor vehicle collision (7), diving (6), gunshot wounds (4), falls (4),
      athletic injuries (3), bicycle collision (2), heavy object falling on spine (2),
      and motorcycle collision (1). Elapsed time from injury to surgery was 40 days
      (range, 3-112 days). Seven (24%) of the 29 patients who were evaluated for the DP
      placement had nonstimulatable diaphragms from either phrenic nerve damage or
      infarction of the involved phrenic motor neurons and were not implanted. Of the
      stimulatable patients undergoing DP, 72% (16 of 22) were completely free of
      ventilator support in an average of 10.2 days. For the remaining six DP patients,
      two had delayed weans of 180 days, three had partial weans using DP at times
      during the day, and one patient successfully implanted went to a long-term acute
      care hospital and subsequently had life-prolonging measures withdrawn. Eight
      patients (36%) had complete recovery of respiration, and DP wires were removed.
      CONCLUSION: Early laparoscopic diaphragm mapping and DP implantation can
      successfully wean traumatic cervical SCI patients from ventilator support. Early
      laparoscopic mapping is also diagnostic in that a nonstimulatable diaphragm is a
      convincing evidence of an inability to wean from ventilator support, and long
      term ventilator management can be immediately instituted. LEVEL OF EVIDENCE:
      Therapeutic study, level V.

PMID- 24458039
TI  - Computer versus paper system for recognition and management of sepsis in surgical
      intensive care.
AB  - BACKGROUND: A system to provide surveillance, diagnosis, and protocolized
      management of surgical intensive care unit (SICU) sepsis was undertaken as a
      performance improvement project. A system for sepsis management was implemented
      for SICU patients using paper followed by a computerized system. The hypothesis
      was that the computerized system would be associated with improved process and
      outcomes. METHODS: A system was designed to provide early recognition and guide
      patient-specific management of sepsis including (1) modified early warning signs
      sepsis recognition score (MEWS-SRS; summative point score of ranges of vital
      signs, mental status, white blood cell count; after every 4 hours) by bedside
      nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary
      tract, soft tissue, other) at bedside by physician or extender; (3) sepsis
      management protocol (replicable, point-of-care decisions) at bedside by nurse,
      physician, and extender. The system was implemented first using paper and then a
      computerized system. Sepsis severity was defined using standard criteria.
      RESULTS: In January to May 2012, a paper system was used to manage 77 consecutive
      sepsis encounters (3.9 +/- 0.5 cases per week) in 65 patients (77% male; age, 53
      +/- 2 years). In June to December 2012, a computerized system was used to manage
      132 consecutive sepsis encounters (4.4 +/- 0.4 cases per week) in 119 patients
      (63% male; age, 58 +/- 2 years). MEWS-SRS elicited 683 site assessments, and 201
      had sepsis diagnosis and protocol management. The predominant site of infection
      was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to
      occur more using the computerized system (paper, 23%; computer, 35%). Hospital
      mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with
      the computerized system. CONCLUSION: A computerized sepsis management system
      improves care process and outcome. Early sepsis is recognized and managed with
      greater frequency compared with severe sepsis or septic shock. The system has a
      beneficial effect as a clinical standard of care for SICU patients. LEVEL OF
      EVIDENCE: Therapeutic study, level III.

PMID- 24458041
TI  - How much and what type: analysis of the first year of the acute care surgery
      operative case log.
AB  - BACKGROUND: A case log was created by the American Association for the Surgery of
      Trauma Acute Care Surgery (ACS) committee to track trainee operative experiences,
      allowing them to enter their cases in the form of Current Procedural Terminology
      (CPT) codes. We hypothesized that the number of cases an ACS trainee performed
      would be similar to the expectations of a fifth-year general surgery resident and
      that the current list of essential and desired cases (E/D list) would accurately
      reflect cases done by ACS trainees. METHODS: The database was queried from July
      1, 2011, to June 30, 2012. Trainees were classified as those in American
      Association for the Surgery of Trauma-accredited fellowships (ACC) and those in
      ACS fellowships not accredited (non-ACC). CPT codes were mapped to the E/D list.
      Cases entered manually were individually reviewed and assigned a CPT code if
      possible or listed as "noncodable." To compensate for nonoperative rotations and
      noncompliance, case numbers were analyzed both annually and monthly to estimate
      average case numbers for all trainees. In addition, case logs of trainees were
      compared with the E/D list to assess how well it reflected actual trainee
      experience. RESULTS: Eighteen ACC ACS and 11 non-ACC ACS trainees performed 16.4
      (12.6) cases per month compared with 15.7 (14.2) cases for non-ACC ACS fellows (p
      = 0.71). When annualized, trainees performed, on average, 195 cases per year.
      Annual analysis led to similar results. The E/D list captured only approximately
      50% of the trainees' operative experience. Only 77 cases were categorized as
      pediatric. CONCLUSION: ACS trainees have substantial operative experience
      averaging nearly 200 major cases during their ACS year. However, high variability
      exists in the number of essential or desirable cases being performed with
      approximately 50% of the fellows' operative experience falling outside the E/D
      list of cases. Modification of the fellows' operative experience and/or the
      rotation requirements seems to be needed to provide experience in E/D cases.

PMID- 24458040
TI  - Inhibition of sepsis-induced inflammatory response by beta1-adrenergic
      antagonists.
AB  - BACKGROUND: Although previous studies have described potential benefits of
      nonselective beta-adrenergic antagonist therapy in sepsis, there is a paucity of
      data on the use of beta1-selective antagonists (B1AA). The purposes of this study
      were to describe the effects of B1AA on survival in septic animals and to explore
      for molecular mechanisms of potential treatment benefit. METHODS: C57BL/6 male
      mice received intraperitoneal injection of lipopolysaccharide. Continuous
      infusion of a B1AA (esmolol) or an equal volume of saline (control) was initiated
      at 4 hours after injection. Kaplan-Meier survival analysis at 120 hours was used
      to explore for mortality differences. A subgroup of animals was sacrificed for
      microarray expression analysis. Top candidate genes were validated in vitro and
      in silico. Expression of our candidate genes in a human microarray database
      (GSE28750) was explored. RESULTS: B1AA infusion resulted in increased survival (p
      = 0.001) at 120 hours. Mean survival difference was 23.6 hours (p = 0.002).
      Hazard ratio for mortality with B1AA is 0.43 (95% confidence interval, 0.26
      0.72). Immunologic disease (p = 0.0003-0.036) and cell death/survival (p = 0.0001
      0.042) were significantly associated with improved survival in septic mice
      treated with B1AA. Further analysis of the gene structure revealed that eight
      genes shared common promoter activating sequence for NFKB and/or BRCA1 motifs.
      Analysis of a human sepsis database identified the up-regulation of CAMP (p =
      0.032) and TNFSF10 (p = 0.001) genes in septic patients compared with healthy
      controls. CONCLUSION: Continuous infusion of a B1AA initiated after septic insult
      improves survival at 5 days in a murine model. Benefits may be caused by
      modulation of gene expression in immunologic pathways leading to an increase in
      CAMP and TNFSF10 expression. This observed effect may be explained by the
      activation of NFKB and BRCA1 genes involved in immune response and cell repair
      pathways. Our findings support further investigation of the use of B1AA in the
      treatment of sepsis.

PMID- 24458042
TI  - Making the financial case for a surgeon-directed critical care ultrasound
      program.
AB  - BACKGROUND: We sought to demonstrate that a well-staffed, surgeon-directed,
      critical care ultrasound program (CCUP) is financially sustainable and provides
      administrative and educational support for point-of-care ultrasound. METHODS: The
      CCUP provides a clinical service and training as well as conducts research.
      Initial costs, annual costs (C), revenue (R), and savings (S) were prospectively
      recorded. Using data from the first 3 years, we calculated the projected C, R,
      and S at 5 years. We determined CCUP sustainability by C < R and C < R + S at 3
      years and 5 years. RESULTS: During 36 months, the CCUP covered four surgical
      intensive care units (55 beds). Start-up costs included one basic and one
      cardiovascular device per 25 beds and a data storage system linking reports and
      images to the electronic medical record ($203,650). Billing increased threefold
      from Years 1 to 3, with a 21% increase between Years 2 to 3. Yearly costs
      included 0.5 full-time equivalent (FTE) sonographer and 0.2 FTE surgeon
      ($106,025); this was increased to 1 FTE and 0.25 FTE, respectively, for Years 4
      and 5. The total 3-year cost was $521,725 and projected to be $863,325 by Year 5.
      The total 3-year revenue was $290,775 and projected to be $891,600 at 5 years.
      The total 3-year savings associated with the CCUP was $600,035 and is projected
      to be $1,194,220. With the use of the C < R, the CCUP meets operating expenses at
      Year 3 and covers overall cost at 5 years. If savings are included, then the CCUP
      is sustainable by its third year and is potentially profitable by Year 5.
      CONCLUSION: A surgeon-directed CCUP is financially sustainable, addresses
      administrative issues, and provides valuable training in point-of-care
      ultrasound.

PMID- 24458043
TI  - Early or delayed stabilization in severely injured patients with spinal
      fractures? Current surgical objectivity according to the Trauma Registry of DGU:
      treatment of spine injuries in polytrauma patients.
AB  - BACKGROUND: Because of a lack of evidence, the appropriate timing of surgical
      stabilization of thoracic and lumbar spine injuries in severely injured patients
      is still controversial. Data of a large international trauma register were
      analyzed to investigate the medical care situation of unstable spinal column
      fractures in patients with multiple injuries, so as to examine the outcome
      related to timing of surgical stabilization. METHODS: Data sets of the Trauma
      Registry of German Trauma Society (Deutsche Gesellschaft fur Unfallchirurgie
      [DGU]) (1993-2010) were analyzed. The Trauma Registry of DGU is a prospective,
      multicenter register that provides information on severely injured patients. All
      patients with an Injury Severity Score (ISS) of 16 or greater caused by blunt
      trauma, subsequent treatment of 7 days or more, 16 years or older, and thoracic
      or lumbar spine injuries (spine Abbreviated Injury Scale [AIS] score >= 2) were
      included in our analysis. Patients with relevant spine injuries classified as
      having a spine AIS score of 3 or greater were further analyzed in terms of
      whether they got early (<72 hours) or late (>72 hours) surgical treatment due to
      unstable spinal column fractures. RESULTS: Of 24,974 patients, 8,994 (36.0%) had
      documented spinal injuries (spine AIS score >= 2). A total of 1,309 patients who
      sustained relevant thoracic spine injuries (spine AIS score >= 3) and 994
      patients who experienced lumbar spine trauma and classified as having spine AIS
      score of 3 or greater were more precisely analyzed. Of these, 68.2% and 71.0%,
      respectively, received an early thoracic or lumbar spine fixation. With an
      increase in spinal injury severity, an increase in early stabilization in the
      thoracic and lumbar spine was seen. In the group of patients with early surgical
      stabilization, significantly shorter hospital stays, shorter intensive care unit
      stays, fewer days on mechanical ventilation, and lower rates of sepsis were seen.
      In the case that additional body regions were affected, for example, when
      patients were critically ill, a delayed spinal stabilization was more often
      performed. CONCLUSION: A spinal stabilization at an early stage (<72 hours) is
      presumed to be beneficial. Although some patients may require delay due to
      necessary medical improvement, every reasonable effort should be made to treat
      patients with instable spinal column fractures as soon as possible. If an early
      surgical treatment is feasible, severely injured patients may benefit from a
      shorter period of hospital treatment and a lower rate of complications. LEVEL OF
      EVIDENCE: Therapeutic study, level III.

PMID- 24458044
TI  - Management of pelvic ring fracture patients with a pelvic "blush" on early
      computed tomography.
AB  - BACKGROUND: The sliding computed tomographic (CT) scanner in our trauma
      resuscitation room can be used early in the assessment of pelvic ring fracture
      patients. We determined the association between the presence of a pelvic blush on
      CT scan and the need for pelvic hemorrhage control (PHC). We hypothesized that
      many pelvic blushes found early in the resuscitation phase can be safely managed
      without intervention. METHODS: Contrast-enhanced CT scans of pelvic ring fracture
      (pelvic ring disruption) patients admitted from January 1, 2004, to June 31,
      2012, were reviewed for the presence of a pelvic blush. PHC was defined as
      requiring a surgical or radiologic intervention for pelvic bleeding. A
      subanalysis was performed in "isolated" pelvic fracture/ blush patients (absence
      of a major nonpelvic bleeding source). RESULTS: Overall, 68 (42%) of 162 pelvic
      ring fracture patients and 53 (40%) of 134 isolated pelvic fracture patients had
      a pelvic blush. Of those 32 (47%) and 27 (51%) patients, respectively, required
      PHC. In the absence of a pelvic blush, 87 (93%) of 94 of all and 77 (95%) of 81
      of isolated pelvic fracture patients did not require PHC. Of all patients with a
      pelvic blush and of isolated pelvic blush, those with PHC had a higher Injury
      Severity Score (ISS) (p = 0.01 and p = 0.05), base deficit (p = 0.03 and p =
      0.01), as well as 24-hour and any packed red blood cells requirement (p <0.001
      and p = 0.05; p <0.001 and p = 0.02). In isolated pelvic blush patients, there
      was a trend toward a higher hospital and hemorrhage-related mortality in patients
      with PHC (p = 0.06 and p = 0.06). CONCLUSION: In pelvic ring fracture patients, a
      pelvic blush on early contrast-enhanced CT is a frequent finding. Many patients
      with (particularly isolated) pelvic blushes have stable vital signs and can be
      managed without surgical or radiologic PHC. The need for an intervention for a
      pelvic blush seems to be determined by the presence of clinical signs of ongoing
      bleeding. LEVEL OF EVIDENCE: Therapeutic study, level IV.
      Prognostic/epidemiologic study, level III.

PMID- 24458045
TI  - Role of alveolar macrophages in the regulation of local and systemic inflammation
      after lung contusion.
AB  - BACKGROUND: Blunt chest trauma is an injury that enhances the morbidity and
      mortality rate, particularly in the context of polytrauma. Our previous studies
      showed local and systemic inflammatory alterations after blunt chest trauma in
      mice. This study was designed to determine whether alveolar macrophages (AMPhi)
      have an alleviative role in this posttraumatic inflammation. METHODS: AMPhi of
      male C3H/HeN mice were depleted by instillation of clodronate liposomes into the
      lung before blunt chest trauma induced by a single blast wave. In bronchoalveolar
      lavage, lung homogenates, plasma, and cell culture supernatants of Kupffer cells,
      peripheral blood mononuclear cells, splenic macrophages, and splenocytes isolated
      2 hours or 24 hours after chest trauma mediator concentrations were determined by
      multiplex assay or enzyme-linked immunosorbent assay. RESULTS: In bronchoalveolar
      lavage, AMPhi depletion led to increased monocyte chemoattractant protein 1 and
      regulated and normal T cell expressed and secreted (RANTES) concentrations as
      well as an attenuated increase of interleukin 6 concentrations after chest
      trauma. Bronchoalveolar lavage keratinocyte-derived chemokine concentrations
      increased in nontraumatized but AMPhi-depleted animals with no further change
      after chest trauma. Cytokine concentrations in lung homogenates were altered in
      the same way as in bronchoalveolar lavage early after trauma. In the plasma of
      AMPhi-depleted animals, interleukin 6 concentrations were slightly decreased
      after chest trauma. Depletion of AMPhi abrogated the trauma-induced decrease of
      Kupffer cell chemokine release. Cytokine concentrations of blood monocytes,
      splenic macrophages, and splenocyte supernatants were not influenced by AMPhi
      depletion. CONCLUSION: These depletion experiments show that AMPhi ameliorate the
      inflammatory response after blunt chest trauma. Taken together, this study gives
      relevant insights into the regulative role of AMPhi during the local and systemic
      inflammation after lung contusion.

PMID- 24458046
TI  - Resveratrol attenuates hypoxic injury in a primary hepatocyte model of
      hemorrhagic shock and resuscitation.
AB  - BACKGROUND: Oxidative stress following hemorrhagic shock and resuscitation (HSR)
      is regulated, in part, by inflammatory and apoptotic mediators such as necrosis
      factor kappaB (NF-kappaB) and p53. Sirtuin 1 (Sirt-1) is a metabolic intermediary
      that regulates stress responses by suppressing NF-kappaB and p53 activity.
      Resveratrol is a naturally occurring polyphenolic antioxidant and Sirt-1 agonist.
      The aim of this study was to determine whether resveratrol protects hepatocytes
      following HSR or hypoxia. METHODS: In vivo, HSR was achieved in male rats by
      arterial blood withdrawal to 30 +/- 2 mm Hg for 1 hour before resuscitation with
      or without resveratrol (Res, 30 mg/kg). Hepatic tissue was stained and scored for
      necrosis, interleukin 6, and Sirt-1 expression. In vitro, primary rat hepatocytes
      were subjected to 8 hours of hypoxia without or with Res (100 uM). Cells were
      analyzed immediately or after 6 hours of normoxia, for survival and markers of
      injury (lactate dehydrogenase assay, lipid peroxidation, and mitochondrial
      integrity). Cell lysates were collected for cytochrome c analysis and
      immunoprecipitated using antibodies against NF-kappaB (p65) or p53. RESULTS: In
      vivo, animals subject to HSR exhibited increased expression of markers of
      hepatocyte damage compared with those sham operated, concomitant with lower Sirt
      1 expression. In vitro, hypoxia followed by normoxia resulted in increased cell
      death, an effect that was blunted by Res. Analysis of cell and mitochondrial
      function demonstrated that Res inhibited the detrimental effects of hypoxia in
      isolated hepatocytes. CONCLUSION: Resveratrol prevents cell death in HSR and
      exerts a protective effect on the mitochondria in a hepatocyte model of hypoxic
      injury-reoxygenation possibly via Sirt-1 modulation of p53 and NF-kappaB
      activity.

PMID- 24458047
TI  - The persistent diagnostic challenge of thoracoabdominal stab wounds.
AB  - BACKGROUND: Penetrating thoracoabdominal trauma, with potential injury to two
      anatomic cavities, significantly challenges surgical management, yet this injury
      pattern has not been reviewed across a large patient series. METHODS: The trauma
      registry of a major level 1 center was queried for all adult patients admitted
      with thoracoabdominal stab wounds between January 1996 and December 2011.
      RESULTS: The study identified 617 patients; 11% arrived hypotensive (systolic
      blood pressure < 90 mm Hg), 6.5% had Glasgow Coma Scale (GCS) score less than 8,
      and 3.6% were in cardiac arrest. Of those arriving alive, 350 (59%) of 595
      underwent surgery (88% laparotomy, 3% thoracotomy, and 9% both procedures).
      Nontherapeutic laparotomy was performed on 12.3% of these patients. Cardiac
      injury occurred in 71% (29 of 41) of the patients arriving alive undergoing
      thoracotomy. Among this group, only 1 (2.4%) of 41 had a major thoracic vessel or
      aortic injury without cardiac trauma. Diaphragmatic injury (DI) occurred in 224
      (38%) of 595, with 72 (32.1%) of these 224 demonstrating no computed tomographic
      evidence of DI. Either hollow viscus injury or DI occurred in 50%. Only 36.8% of
      liver, 58% of spleen, and 29.8% of kidney injuries required surgical repair. The
      need for dual-cavitary intervention was associated with a precipitous increase in
      patient mortality. CONCLUSION: Patients with thoracoabdominal stab wounds present
      considerable clinical challenges due to high surgical need, high occult DI
      incidence, persistently high rates of negative laparotomy, and significant
      mortality with dual-cavitary intervention. Many patients with solid-organ
      injuries do not require intervention. High incidence of hollow viscus injury and
      DI ultimately limits nonoperative management. Laparoscopy is necessary to exclude
      occult DI. In unstable patients, determination of which anatomic cavity to
      explore primarily requires exclusion of cardiac injury. In those with equivocal
      clinical or ultrasonographic evidence of cardiac trauma, laparotomy, with
      transdiaphragmatic pericardial window, if a causative abdominal injury is not
      immediately apparent, seems the most effective strategy. LEVEL OF EVIDENCE:
      Epidemiologic study, level III.

PMID- 24458048
TI  - Fulminant Clostridium difficile colitis: prospective development of a risk
      scoring system.
AB  - BACKGROUND: Of the patients with a Clostridium difficile infection, 2% to 8% will
      progress to fulminant C. difficile colitis (fCDC), which carries high morbidity
      and mortality. No system exists to rapidly identify patients at risk for
      developing fCDC and possibly in need of surgical intervention. Our aim was to
      design a simple and accurate risk scoring system (RSS) for daily clinical
      practice. METHODS: We prospectively enrolled all patients diagnosed with a C.
      difficile infection and compared patients with and without fCDC. An expert panel,
      combined with data derived from previous studies, identified four risk factors,
      and a multivariable logistic regression model was performed to determine their
      effect in predicting fCDC. The RSS was created based on the predictive power of
      each factor, and calibration, discrimination, and test characteristics were
      subsequently determined. In addition, the RSS was compared with a previously
      proposed severity scoring system. RESULTS: A total of 746 patients diagnosed with
      C. difficile infection were enrolled between November 2010 and October 2012.
      Based on the log (odds ratio) of each risk factor, age greater than 70 years was
      assigned 2 points, white blood cell count equal to or greater than 20,000/MUL or
      equal to or less than 2,000/MUL was assigned 1 point, cardiorespiratory failure
      was assigned 7 points, and diffuse abdominal tenderness on physical examination
      was assigned 6 points. With the use of this system, the discriminatory value of
      the RSS (c statistic) was 0.98 (95% confidence interval, 0.96-1).The Hosmer
      Lemeshow goodness-of-fit test showed a p value of 0.78, and the Brier score was
      0.019. A value of 6 points was determined to be the threshold for reliably
      dividing low-risk ( <6) from high-risk (>= 6) patients. CONCLUSION: The RSS is a
      valid and reliable tool to identify at the bedside patients who are at risk for
      developing fCDC. External validation is needed before widespread implementation.
      LEVEL OF EVIDENCE: Prognostic study, level II.

PMID- 24458049
TI  - The impact of preinjury anticoagulants and prescription antiplatelet agents on
      outcomes in older patients with traumatic brain injury.
AB  - BACKGROUND: Anticoagulants and prescription antiplatelet (ACAP) agents widely
      used by older adults have the potential to adversely affect traumatic brain
      injury (TBI) outcomes. We hypothesized that TBI patients on preinjury ACAP agents
      would have worse outcomes than non-ACAP patients. METHODS: This was a 5.5-year
      retrospective review of patients 55 years and older admitted to a Level I trauma
      center with blunt force TBI. Patients were categorized as ACAP (warfarin,
      clopidogrel, dipyridamole/aspirin, enoxaparin, subcutaneous heparin, or multiple
      agents) or non-ACAP. ACAP patients were further stratified by class of agent
      (anticoagulant or antiplatelet). Initial and subsequent head computerized
      tomographic results were examined for type and progression of TBI. Patient
      preadmission living status and discharge destination were identified. Primary
      outcome was in-hospital mortality. Secondary outcomes were progression of initial
      TBI, development of new intracranial hemorrhage (remote from initial), and the
      need for an increased level of care at discharge. RESULTS: A total of 353
      patients met inclusion criteria: 273 non-ACAP (77%) and 80 ACAP (23%). Upon
      exclusion of three patients taking a combination of agents, 350 were available
      for advanced analyses. ACAP status was significantly related to in-hospital
      mortality. After adjustment for patient and injury characteristics, anticoagulant
      users were more likely than non-ACAP patients to show progression of initial
      hemorrhage and develop a new hemorrhagic focus. However, compared with non-ACAP
      users, antiplatelet users were more likely to die in the hospital. Among
      survivors to discharge, anticoagulant users were more likely to be discharged to
      a care facility, but this finding was not robust to adjustment. CONCLUSION: Older
      TBI patients on preinjury ACAP agents experience a comparatively higher rate of
      inpatient mortality and other adverse outcomes caused by the effects of
      antiplatelet agents. Our findings should inform decision making regarding
      prognosis and caution against grouping anticoagulant and antiplatelet users
      together in considering outcomes. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 24458050
TI  - Effect of a dalteparin prophylaxis protocol using anti-factor Xa concentrations
      on venous thromboembolism in high-risk trauma patients.
AB  - BACKGROUND: Low anti-factor Xa (anti-Xa) concentrations with twice-daily
      enoxaparin are associated with venous thromboembolism (VTE) in high-risk trauma
      patients. Concerns have been raised with once-daily dalteparin regarding
      effectiveness and achievable anti-Xa concentrations. The purpose of this before
      and-after study was to evaluate the effectiveness of a VTE prophylaxis protocol
      using anti-Xa concentrations and associated dalteparin dose adjustment in high
      risk trauma patients. METHODS: Adult trauma patients receiving VTE
      chemoprophylaxis and hospitalized for at least 3 days were prospectively followed
      during two 6-month epochs before (PRE) and after (POST) implementation of anti-Xa
      monitoring. In both groups, high-risk patients received dalteparin 5,000 U
      subcutaneously once daily; low-risk patients received subcutaneous unfractionated
      heparin. High-risk POST patients with anti-Xa less than 0.1 IU/mL 12 hours after
      initial dalteparin dose received dalteparin every 12 hours. All patients
      underwent routine VTE ultrasound surveillance of the lower extremities. The
      primary outcome was incidence of VTE. RESULTS: A total of 785 patients (PRE, n =
      428; POST, n = 357) were included. Demographics, injury patterns, Injury Severity
      Score (ISS), red blood cell transfusions, intensive care unit and hospital stays,
      and mortality did not differ between groups. Overall, POST patients had lower VTE
      (7.0% vs. 13%, p = 0.009) including acute VTE (6.4% vs. 12%, p = 0.01) and
      proximal deep vein thromboembolism (2.2% vs. 5.7%, p = 0.019). Between high-risk
      patients, VTE occurred in 53 (16.3%) PRE compared with 24 (9.0%) POST patients (p
      = 0.01); there was no difference in VTE between low-risk patients (PRE, 2.0% vs.
      POST, 1.1%; p = 0.86). Among 190 high-risk POST patients with anti-Xa, 97 (51%)
      were less than 0.1 IU/mL. Patients with low anti-Xa had higher rates of VTE
      (14.0% vs. 5.4%, p = 0.05) and deep vein thromboembolism (14.4% vs. 3.2%, p =
      0.01). Younger age (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) and
      greater weight (odds ratio, 1.02; 95% confidence interval, 1.00-1.03) predicted
      low anti-Xa on multivariate regression. CONCLUSION: A VTE prophylaxis protocol
      using anti-Xa-based dalteparin dosage adjustment in high-risk trauma patients was
      associated with decreased VTE. Once-daily dalteparin 12-hour anti-Xa
      concentrations are suboptimal in a majority of patients and associated with VTE.
      LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 24458051
TI  - Flail chest injuries: a review of outcomes and treatment practices from the
      National Trauma Data Bank.
AB  - BACKGROUND: Flail chest injuries are associated with severe pulmonary
      restriction, a requirement for intubation and mechanical ventilation, and high
      rates of morbidity and mortality. Our goals were to investigate the prevalence,
      current treatment practices, and outcomes of flail chest injuries in polytrauma
      patients. METHODS: The National Trauma Data Bank was used for a retrospective
      analysis of the injury patterns, management, and clinical outcomes associated
      with flail chest injuries. Patients with a flail chest injury admitted from 2007
      to 2009 were included in the analysis. Outcomes included the number of days on
      mechanical ventilation, days in the intensive care unit (ICU), days in the
      hospital, and rates of pneumonia, sepsis, tracheostomy, chest tube placement, and
      death. RESULTS: Flail chest injury was identified in 3,467 patients; the mean age
      was 52.5 years, and 77% of the patients were male. Significant head injury was
      present in 15%, while 54% had lung contusions. Treatment practices included
      epidural catheters in 8% and surgical fixation of the chest wall in 0.7% of the
      patients. Mechanical ventilation was required in 59%, for a mean of 12.1 days.
      ICU admission was required in 82%, for a mean of 11.7 days. Chest tubes were used
      in 44%, and 21% required a tracheostomy. Complications included pneumonia in 21%,
      adult respiratory distress syndrome in 14%, sepsis in 7%, and death in 16%.
      Patients with concurrent severe head injury had higher rates of ventilatory
      support and ICU stay and had worse outcomes in every category compared with those
      without a head injury. CONCLUSION: Patients who have sustained a flail chest have
      significant morbidity and mortality. More than 99% of these patients were treated
      nonoperatively, and only a small proportion (8%) received aggressive pain
      management with epidural catheters. Given the high rates of morbidity and
      mortality in patients with a flail chest injury, alternate methods of treatment
      including more consistent use of epidural catheters for pain or surgical fixation
      need to be investigated with large randomized controlled trials. LEVEL OF
      EVIDENCE: Epidemiologic/prognostic study, level IV.

PMID- 24458052
TI  - Evaluation of the oxygenation index in adult respiratory failure.
AB  - BACKGROUND: The oxygenation index (mean airway pressure * FIO2 divided by PaO2)
      was originally devised to measure severity of illness and predict outcome in
      neonatal respiratory failure. We evaluated the discrimination of a modified
      oxygenation index (modified with age) for predicting 28-day mortality in adults
      with respiratory failure (adult respiratory distress syndrome [ARDS]) using the
      ALVEOLI section of the ARDSNet database and validated the results in the full
      ARDSNet database. METHODS: We compared age-adjusted oxygenation index (AOI) on
      ventilator Days 1 to 4 with 28-day mortality. RESULTS: AOI correlated positively
      with mortality (area under the receiver operating characteristic curve, 0.70
      0.74, for ARDS Days 1-4). Following initial development, AOI related to mortality
      was validated in two other ARDSNet databases producing similar results (area
      under the receiver operating characteristic curve, 0.70-0.78). CONCLUSION: The
      observed sensitivity and specificity analysis demonstrated that AOI is equivalent
      to or better than other mortality prediction systems used for ARDS. LEVEL OF
      EVIDENCE: Prognostic, level III.

PMID- 24458053
TI  - Do one-time intracompartmental pressure measurements have a high false-positive
      rate in diagnosing compartment syndrome?
AB  - BACKGROUND: Intracompartmental pressure measurements are frequently used in the
      diagnosis of compartment syndrome, particularly in patients with equivocal or
      limited physical examination findings. Little clinical work has been done to
      validate the clinical use of intracompartmental pressures or identify associated
      false-positive rates. We hypothesized that diagnosis of compartment syndrome
      based on one-time pressure measurements alone is associated with a high false
      positive rate. METHODS: Forty-eight consecutive patients with tibial shaft
      fractures who were not suspected of having compartment syndrome based on physical
      examinations were prospectively enrolled. Pressure measurements were obtained in
      all four compartments at a single point in time immediately after induction of
      anesthesia using a pressure-monitoring device. Preoperative and intraoperative
      blood pressure measurements were recorded. The same standardized examination was
      performed by the attending surgeon preoperatively, postoperatively, and during
      clinical follow-up for 6 months to assess clinical evidence of acute or late
      compartment syndrome. RESULTS: No clinical evidence of compartment syndrome was
      observed postoperatively or during follow-up until 6 months after injury. Using
      the accepted criteria of delta P of 30 mm Hg from preoperative diastolic blood
      pressure, 35% of cases (n = 16; 95% confidence interval, 21.5-48.5%) met criteria
      for compartment syndrome. Raising the threshold to delta P of 20 mm Hg reduced
      the false-positive rate to 24% (n = 11; 95% confidence interval, 11.1-34.9%).
      Twenty-two percent (n = 10; 95% confidence interval, 9.5-32.5%) exceeded absolute
      pressure of 45 mm Hg. CONCLUSION: A 35% false-positive rate was found for the
      diagnosis of compartment syndrome in patients with tibial shaft fractures who
      were not thought to have compartment syndrome by using currently accepted
      criteria for diagnosis based solely on one-time compartment pressure
      measurements. Our data suggest that reliance on one-time intracompartmental
      pressure measurements can overestimate the rate of compartment syndrome and raise
      concern regarding unnecessary fasciotomies. LEVEL OF EVIDENCE: Diagnostic study,
      level II.

PMID- 24458054
TI  - Should blunt segmental vascular renal injuries be considered an American
      Association for the Surgery of Trauma Grade 4 renal injury?
AB  - BACKGROUND: Renal segmental vascular injury (SVI) following blunt abdominal
      trauma is not part of the original American Association for the Surgery of Trauma
      (AAST) renal injury grading system. Recent recommendations support classifying
      SVI as an AAST Grade 4 (G4) injury. Our primary aim was to compare outcomes
      following blunt renal SVI and blunt renal collecting system lacerations (CSLs).
      We hypothesize that renal SVI fare well with conservative management alone and
      should be relegated a less severe renal AAST grade. METHODS: We retrospectively
      identified patients with SVI and G4 CSL admitted to a Level 1 trauma center
      between 2003 and 2010. Penetrating trauma was excluded. Need for surgical
      intervention, length of stay, kidney salvage (>25% renal preservation on
      renography 6-12 weeks after injury), and delayed complication rates were compared
      between the SVI and CSL injuries. Statistical analysis used chi, Fisher's exact,
      and t tests. RESULTS: A total of 56 patients with SVI and 88 patients with G4 CSL
      sustained blunt trauma. Age, Injury Severity Score (ISS), and length of stay were
      similar for the two groups. Five patients in each group died of concomitant,
      nonrenal injuries. In the G4 CSL group, 15 patients underwent major
      interventions, and 32 patients underwent minor interventions. Only one patient in
      the SVI group underwent a major intervention. The renal salvage rate was 85.7%
      following SVI versus 62.5% following CSL (p = 0.107). CONCLUSION: Overall,
      surgical interventions are significantly lower among the SVI cohort than the G4
      CSL cohort. Further analysis using a larger cohort of patients is recommended
      before revising the current renal grading system. Adding SVI as a G4 injury could
      potentially increase the heterogeneity of G4 injuries and decrease the ability of
      the AAST renal injury grading system to predict outcomes, such as nephrectomy
      rate. LEVEL OF EVIDENCE: Epidemiologic study, level IV.

PMID- 24458055
TI  - Frontal sinus volume predicts incidence of brain contusion in patients with head
      trauma.
AB  - BACKGROUND: The function of the paranasal sinuses is a topic of debate. One
      hypothesis suggested has been that sinuses act as a "crumple zone," serving to
      protect the contents of the head from impact. In this study, we examine the
      interactions of the frontal sinus and the brain in the setting of head trauma.
      Our formal hypothesis is that frontal sinus volume is less in head trauma
      patients with contusion than in head trauma patients without contusion. METHODS:
      Computed tomographic (CT) scans of patients who sustained blunt head trauma
      performed at the University of Pittsburgh Medical Center from 2007 to 2012 were
      reviewed retrospectively. Inclusion criteria were presence of blunt trauma and
      complete brain and maxillofacial CT scan. Exclusion criteria included patients
      with incomplete imaging, imaging unrelated to trauma, previous cranial injury,
      and penetrating trauma.With the use of maxillofacial CT scans, height, depth, and
      width were measured, and a cubical approximation of volume was determined for
      each frontal sinus. Presence of frontal sinus fracture was considered an
      indicator of high-impact trauma. Grading of brain contusion severity was
      performed using head CT scans. A scale of 0 to 5 was used based on the Marshall
      Criteria.Categorical data were analyzed using the chi(2) or Fisher's exact test.
      Continuous data were analyzed using Student's t test or analysis of variance. p <
      0.05 was considered statistically significant. RESULTS: Among patients with
      frontal sinus fracture, the average sinus volume of those without contusion was
      32.72 mL, while the average sinus volume of those with brain contusion was 21.85
      mL (p = 0.023). Thus, the volume of the frontal sinuses was 33% less in patients
      with contusion than in patients without contusion. CONCLUSION: Our study supports
      the theory that the frontal sinuses impart a protective advantage against frontal
      brain contusion. The dynamics of head injury and force distribution during trauma
      may be the basis for more advanced protective devices. LEVEL OF EVIDENCE:
      Prognostic study, level III.

PMID- 24458056
TI  - The Mayo Clinic experience with Morel-Lavallee lesions: establishment of a
      practice management guideline.
AB  - BACKGROUND: Although uncommon, Morel-Lavallee lesions (also called closed
      degloving injuries) are associated with considerable morbidity in trauma
      patients. There is lack of consensus regarding proper management of these
      lesions. Management options include nonoperative therapies, along with
      percutaneous and operative techniques. We sought to define the factors associated
      with failure of percutaneous aspiration to better identify patients requiring
      immediate operative management. METHODS: We retrospectively searched our
      prospectively collected database for patient records containing the terms Morel
      Lavallee, closed degloving injury, or posttraumatic seroma from February 2, 2004,
      through December 23, 2011. Treatment methods included compression wraps or
      observation (nonoperative management), percutaneous aspiration, or operative
      management with incision/drainage or formal debridement of skin and soft tissues
      that resulted in wound vacuum-assisted closure placement and/or split-thickness
      skin graft (operative management). The treatment groups were compared using
      univariate analysis and chi testing. RESULTS: We identified 79 patients with 87
      Morel-Lavallee lesions in the setting of trauma. Most were caused by motor
      vehicle collisions (25%). No difference was observed between the treatment groups
      in sex, body mass index, anticoagulation treatment, diabetes mellitus, smoking
      history, or alcohol use. The percutaneous aspiration group had higher rates of
      recurrence (56% vs. 19% and 15% in nonoperative and operative groups,
      respectively). The percentage of patients who had aspiration of more than 50 mL
      of fluid was higher for lesions that recurred than for lesions that resolved (83%
      vs. 33%, p = 0.02). CONCLUSION: Aspiration of more than 50 mL of fluid from Morel
      Lavallee lesions was much more common among lesions that recurred (83%) than
      among those that resolved (33%). We therefore recommend that aspiration of more
      than 50 mL of fluid from a Morel-Lavallee lesion prompts operative intervention.
      We have now adopted this as a practice management guideline. LEVEL OF EVIDENCE:
      Therapeutic/care management study, level III.

PMID- 24458057
TI  - Long-term outcomes of ground-level falls in the elderly.
AB  - BACKGROUND: For older adults, even ground-level falls (GLFs) can result in
      multiple injuries and are associated with significant morbidity and mortality.
      Previous studies have focused on in-hospital outcomes and patients with isolated
      injuries. Our study examined outcomes following discharge for older adults who
      were hospitalized following a GLF. METHODS: A retrospective cohort study of
      patients older than 65 years admitted to a regional Level I trauma center, from
      2005 to 2008, after a GLF was conducted. Hospital trauma registry data were
      linked to state hospital discharge data and the death certificate registry.
      Skilled nursing facilities (SNFs) were contacted to verify ultimate patient
      placement, with follow-up through December 2010. Kaplan-Meier and Cox
      proportional hazards models were used to analyze postdischarge mortality.
      RESULTS: There were 1,352 consecutive admissions; 48% had an Injury Severity
      Score (ISS) greater than 15, and 12% died during admission. Of the patients who
      survived hospitalization, 51% were discharged to an SNF, 33% to home without
      assistance, 6% to home with assistance, and 5% to inpatient rehabilitation
      facilities. Within 1 year of injury, 44.6% of the patients were readmitted. The 1
      year mortality for the overall cohort was 33%; for patients who were discharged
      alive, the 1-year mortality was 24%. After adjusting for confounders, patients
      discharged to an SNF had a threefold greater risk of 1-year mortality (hazard
      ratio, 2.82; 95% confidence interval, 1.86-4.28), compared with patients
      discharged home with no assistance. Of the patients discharged to an SNF, 48%
      died by the end of the follow-up period (mean, 28.2 months), and 61% of these
      patients died while residing at an SNF. CONCLUSION: GLFs in the elderly result in
      severe injury, high rate of readmissions, and increased mortality, both in
      hospital and after discharge. Overall, only one third of the patients were
      discharged home to independent living. Future efforts should examine whether
      improvements in the quality of posthospital care affect both mortality and
      functional outcomes. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level
      III.

PMID- 24458058
TI  - Traumatic brain injury and beta-blockers: not all drugs are created equal.
AB  - BACKGROUND: Dysautonomia in traumatic brain injury patients may contribute to
      secondary injury. We hypothesize that propranolol is the best beta-blocker (BB)
      to block the excess catecholamines and improve mortality in this patient
      population. METHODS: Patients with traumatic brain injury admitted during a 48
      month period who received BB were compared with those who did not after excluding
      patients who received preinjury BB, deaths within 48 hours, and head Abbreviated
      Injury Scale (AIS) score of less than 3 or greater than 5. In addition,
      propranolol was also compared with all other BBs. RESULTS: A total of 1,755
      patients with traumatic brain injury were identified during the study period
      after exclusions. Patients who received BB (427) were older (49 years vs. 40
      years; p < 0.0001), were more severely injured (Injury Severity Score [ISS], 30
      vs. 24; p < 0.001), and had a more severe head injury (head AIS score, 4.2 vs.
      4.0; p < 0.001). By univariate analysis, BB patients had a higher mortality (13%
      vs. 6%; p < 0.001); after adjusted analysis, no difference was identified
      (adjusted odds ratio, 0.850; 95% confidence interval, 0.536-1.348). Seventy-eight
      patients (18%) received propranolol during the study period. Propranolol patients
      were younger (30 years vs. 53 years; p < 0.001) but more severely injured (ISS,
      33 vs. 29; p = 0.01; head AIS, 4.5 vs. 4.2; p < 0.001), with longer stay (44 days
      vs. 26 days, p < 0.001). Mortality was less in the propranolol group (3% vs. 15%,
      p = 0.002). Adjusted analysis confirmed the protective effect of propranolol
      (adjusted odds ratio, 0.199; 95% confidence interval, 0.043-0.920). CONCLUSION:
      Propranolol is the best BB to limit secondary injury and decrease mortality in
      patients with traumatic brain injury. LEVEL OF EVIDENCE: Therapeutic, study level
      III.

PMID- 24458059
TI  - Outcomes of endovascular repair for patients with blunt traumatic aortic injury.
AB  - BACKGROUND: Traumatic aortic injury (TAI) remains a leading cause of death after
      blunt force. Thoracic endovascular aortic repair (TEVAR) has been widely adopted
      as an alternative to open repair for the treatment of TAI. Although significant
      short-term benefits have been demonstrated for patients undergoing TEVAR, longer
      term follow-up data are lacking. METHODS: Trauma registry data were analyzed.
      Follow-up data were gathered from a combination of medical records, imaging,
      telephone interviews, and Social Security Death Index. Primary outcomes were in
      hospital mortality, stroke, and paraplegia. Secondary outcomes included device
      related adverse events (rupture, migration, or endoleak), secondary procedures,
      open conversion, and all-cause mortality. RESULTS: Between September 2005 and
      July 2012, 82 consecutive patients (57 males, mean [SD] age, 39.5 [20] years;
      mean [SD] Injury Severity Score [ISS], 34 [9.5]) underwent TEVAR for TAI. A total
      of 87 devices were implanted: TAG (n = 36), CTAG (n = 12) (WL Gore, Flagstaff,
      AZ); Talent (n = 29), Valiant (n = 5) (Medtronic, Santa Rosa, CA); TX2 (n = 2)
      (Cook, Bloomington, IN); and other (n = 3). Left subclavian artery coverage was
      required in 32 patients (39%). Technical success rate was 100%. Rates of in
      hospital mortality, stroke, and paraplegia were 5.0%, 2.4%, and 0%,
      respectively.Median follow-up time was 2.3 years (range, 0-7 years). The
      availability of follow-up data was as follows: Social Security Death Index
      (100%), telephone interview (68%), clinic visit (61%), and imaging (82%). The
      incidence of device-related adverse events was 2.4%. There were four secondary
      procedures: two patients underwent a carotid-subclavian bypass, and two had an
      open conversion for device-related complications. Survival was 95% at 30 days,
      88% at 1 year, 87% at 2 years, and 82% at 5 years. CONCLUSION: At midterm follow
      up, TEVAR is an effective and durable option for the treatment of TAI in properly
      selected patients. Device-related adverse events, secondary procedures, and open
      conversion are rare. Follow-up remains a challenge. LEVEL OF EVIDENCE:
      Therapeutic study, level V.

PMID- 24458060
TI  - Posttraumatic stress disorder following traumatic injury at 6 months:
      associations with alcohol use and depression.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is progressively recognized as a
      psychological morbidity in injured patients. Participants in a longitudinal study
      were identified as PTSD positive or PTSD negative at 6 months following injury.
      Risky alcohol use, depression, demographic, and injury-related variables were
      explored. METHODS: This prospective cohort included patients 18 years or older,
      admitted to our Level I trauma center. Outcome measures included PTSD Checklist
      Civilian Version (PCL-C), Alcohol Use Disorders Identification Test (AUDIT-C),
      and Patient Health Questionnaire (PHQ-8). Demographic and injury variables were
      collected. RESULTS: A total of 211 participants enrolled in the study, and 118
      participants completed measures at both baseline and 6 months. Of the
      participants, 25.4% (n = 30) screened positive for PTSD at 6 months. The entire
      sample showed a decline in risky alcohol use at 6 months (p = 0.0043). All PTSD
      positive participants at 6 months were also positive for depression (p < 0.0001).
      For the entire sample, there was a 10% increase in depression from baseline to 6
      months (p = 0.03). However, for those participants who were PTSD positive at 6
      months, there was a 53% increase in depression from baseline (p = 0.0002) as
      compared with the group at 6 months without PTSD. Statistically significant
      differences were found between PTSD-positive and PTSD-negative participants
      regarding age (40.1 [15.9] vs. 50.9 [18.2], p = 0.0047), male (77% vs. 50%, p =
      0.0109), penetrating injury (30% vs. 4%, p < 0.0001), PTSD history (17% vs. 4%, p
      = 0.0246), or other psychiatric condition (63% vs. 19%, p <= 0.001). CONCLUSION:
      PTSD was not associated with risky alcohol use at 6 months. Surprisingly, risky
      alcohol use declined in both groups. Incidence of PTSD (25.4%, n = 30) and risky
      alcohol use (25%, n = 29) were equal at 6 months. Although the American College
      of Surgeons' Committee on Trauma requires brief screening and intervention for
      risky alcohol use owing to societal impact, reinjury rates, and cost
      effectiveness, our study suggests that screening for psychological conditions may
      be equally important. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 24458061
TI  - Outcomes of acute versus elective primary ventral hernia repair.
AB  - BACKGROUND: The morbidity and mortality associated with acute primary ventral
      hernia repair have not been well described. We examined the rate of surgical site
      infection (SSI), hernia recurrence, and mortality in acute versus elective
      primary ventral hernia repair and identified predictors of morbidity and
      mortality after primary ventral hernia repair. METHODS: A retrospective study on
      all patients undergoing open primary ventral hernia repair at a single
      institution (2000-2010) was performed. Primary outcomes were mortality at any
      time, SSI, and recurrence. Survival analysis for the entire, unmatched sample was
      conducted. We performed a risk-adjusted analysis of outcomes using two methods as
      follows: (1) case matching and (2) propensity score-adjusted regression model.
      RESULTS: We identified 497 patients; 57 (11%) underwent acute primary ventral
      hernia repair. For the entire cohort, survival was worse for patients undergoing
      acute repair (log rank, 0.03). Following case matching on age, body mass index,
      American Society of Anesthesiologists score, and hernia size, there was no
      difference in mortality, SSI, or recurrence. After propensity score adjustment,
      acute surgery was not a predictor for mortality or SSI; however, incarcerated
      hernias predicted recurrence. CONCLUSION: After risk adjustment, acute primary
      ventral hernia repair was not associated with higher mortality, infection, or
      recurrence compared with elective repair. LEVEL OF EVIDENCE: Therapeutic study,
      level IV.

PMID- 24458062
TI  - The financial impact of the loss of county indigent patient funding on a single
      orthopedic trauma surgery service.
AB  - BACKGROUND: We examined the financial ramifications on the orthopedic trauma
      service after loss of payment to our institution for care of indigent patients.
      Our institution is the only Level I trauma center located within the county.
      Before mid-2009, county insurance-eligible patients treated at our institution
      had their health care paid for by the county. After mid-2009, the county no
      longer reimbursed our institution for care provided. METHODS: A retrospective
      review was performed on 653 county patients treated by the four orthopedic trauma
      surgeons during a 4-year period including the 2 years before the loss of county
      payments as well as the 2-year period following the loss of payment. Data
      collected included demographics, admitting service, injuries treated, length of
      stay, surgeon billing, and reimbursement. We also classified the urgency of care
      that was rendered into one of three categories as follows: emergent, urgent, or
      elective. RESULTS: There was a higher frequency of emergent and urgent procedures
      and a lower frequency of elective cases performed in the noncontracted period
      versus the contracted period. During the contracted period, we billed and
      collected $1,161,036. After the loss of reimbursement from the county, we billed
      $870,590 and were paid $0. County reimbursements made up 33.5% of the total
      professional fees billed. There was a 20% net drop in total billing during the
      noncontracted period, of which the money not reimbursed by the county accounted
      for 31%. CONCLUSION: Despite the lack of county payment, our institution
      continues to provide care to the indigent population. This lack of payment may
      have significant long-term economic ramifications for the orthopedic trauma
      surgeons and for our institution. The financial burden preferentially falls on
      the "safety net" Level I trauma centers and the physicians who take care of
      patients with urgent and emergent injuries. This burden may be unsustainable in
      the future. LEVEL OF EVIDENCE: Economic and value-based evaluation, level V.

PMID- 24458063
TI  - Cost-utility analysis of prehospital spine immobilization recommendations for
      penetrating trauma.
AB  - BACKGROUND: The American College of Surgeons' Committee on Trauma's recent
      prehospital trauma life support recommendations against prehospital spine
      immobilization (PHSI) after penetrating trauma are based on a low incidence of
      unstable spine injuries after penetrating injuries. However, given the chronic
      and costly nature of devastating spine injuries, the cost-utility of PHSI is
      unclear. Our hypothesis was that the cost-utility of PHSI in penetrating trauma
      precludes routine use of this prevention strategy. METHODS: A Markov model based
      cost-utility analysis was performed from a society perspective of a hypothetical
      cohort of 20-year-old males presenting with penetrating trauma and transported to
      a US hospital. The analysis compared PHSI with observation alone. The
      probabilities of spine injuries, costs (US 2010 dollars), and utility of the two
      groups were derived from published studies and public data. Incremental
      effectiveness was measured in quality-adjusted life-years. Subset analyses of
      isolated head and neck injuries as well as sensitivity analyses were performed to
      assess the strength of the recommendations. RESULTS: Only 0.2% of penetrating
      trauma produced unstable spine injury, and only 7.4% of the patients with
      unstable spine injury who underwent spine stabilization had neurologic
      improvement. The total lifetime per-patient cost was $930,446 for the PHSI group
      versus $929,883 for the nonimmobilization group, with no difference in overall
      quality-adjusted life-years. Subset analysis demonstrated that PHSI for patients
      with isolated head or neck injuries provided equivocal benefit over
      nonimmobilization. CONCLUSION: PHSI was not cost-effective for patients with
      torso or extremity penetrating trauma. Despite increased incidence of unstable
      spine injures produced by penetrating head or neck injuries, the cost-benefit of
      PHSI in these patients is equivocal, and further studies may be needed before
      omitting PHSI in patients with penetrating head and neck injuries. LEVEL OF
      EVIDENCE: Economic and value-based evaluation, level II.

PMID- 24458064
TI  - Trauma center performance evaluation based on costs: a systematic review of
      cohort studies.
AB  - BACKGROUND: In 2000, more than 50 million Americans were treated in hospitals
      following injury, with costs estimated at $80 billion, yet no performance
      indicator based on costs has been developed and validated specifically for acute
      trauma care. This study aimed to describe how data on costs have been used to
      evaluate the performance of acute trauma care hospitals. METHODS: A systematic
      review using MEDLINE, EMBASE, Web of Science, The Cochrane Library, CINAHL, TRIP,
      and ProQuest was performed in December 2012. Cohort studies evaluating hospital
      performance for the treatment of injury inpatients in terms of costs were
      considered eligible. Two authors conducted the screening and the data abstraction
      independently using a piloted electronic data abstraction form. Methodological
      quality was evaluated using seven criteria from the Strengthening the Reporting
      of Observational Studies in Epidemiology (STROBE) statement and the Downs and
      Black tool. RESULTS: The search retrieved 6,635 studies, of which 10 were
      eligible for inclusion. Nine studies were conducted in the United States and one
      in Europe. Six studies used patient charges as a proxy for patient costs, of
      which four used cost-to-charge ratios. One study estimated costs using average
      unit costs, and three studies were based on the real costs obtained from a
      hospital accounting system. Average costs per patient in 2013 US dollar varied
      between 2,568 and 74,435. Four studies (40%) were considered to be of good
      methodological quality. CONCLUSION: Studies evaluating the performance of trauma
      hospitals in terms of costs are rare. Most are based on charges rather than
      costs, and they have low methodological quality. Further research is needed to
      develop and validate a performance indicator based on inpatient costs that will
      enable us to monitor trauma centers in terms of resource use. LEVEL OF EVIDENCE:
      Systematic review, evidence, level III.

PMID- 24458067
TI  - Robot-assisted resection of choledochal cysts and hepaticojejunostomy in
      children.
AB  - PURPOSE: Choledochal cysts have traditionally been treated as an open procedure.
      However, recent publications from some large volume centres show that minimally
      invasive surgery has become their standard approach. Robotic surgical systems
      facilitate a surgeon's ability to undertake complex procedures. We present our
      experience of using robot assistance to treat choledochal cysts. METHODS:
      Children admitted with a choledochal cyst from March 2009 to Nov 2012 were
      included. There were 27 patients (20 females). Mean age 5.4 years (range 0.3
      15.9). Mean weight 21.9 kg (range 5.9-78.8); 10 weighed <10 kg. The choledochal
      cysts were types 1c(12), 1f(10) and 4(5). The da vinci Surgical System was used
      for the robot-assisted resection of the choledochal cyst and hepaticojejunostomy.
      Roux loop was fashioned extra-corporeally. Mean follow-up is 2.7 years (range 0.9
      4.7). RESULTS: 22 cases were completed successfully with robotic assistance. Five
      open conversions were for anatomical concerns or technical reasons. One child had
      three complications (omental hernia, anastomotic stricture and subsequent bile
      leak). Patients were on full feeds by a median of 5 days (range 3-6) and
      discharged after 6 days (range 4-7). CONCLUSION: Robotic-assisted resection of
      choledochal cysts in children is safe. They made a rapid recovery with a good
      cosmetic outcome.

PMID- 24458068
TI  - Hydroxyamination of aryl C-H bonds with N-hydroxycarbamate by synergistic Rh/Cu
      catalysis at room temperature.
AB  - A novel hydroamination of aryl C-H bonds has been accomplished using N-Boc
      hydroxyamine via synergistic combination of rhodium and copper catalysis. The
      merger of two robust catalytic systems has allowed for the development of a mild
      and sustainable protocol for the direct formation of benzo[c]isoxazol-3(1H)-ones.

PMID- 24458069
TI  - Do omega-3 polyunsaturated fatty acids prevent atrial fibrillation?

PMID- 24458070
TI  - Prevalence and correlates of metabolic acidosis among patients with homozygous
      sickle cell disease.
AB  - BACKGROUND AND OBJECTIVES: Very few studies report acid base disorders in
      homozygous patients with sickle cell anemia (SCA) and describe incomplete renal
      acidosis rather than true metabolic acidosis, the prevalence of which is unknown
      and presumably low. This study aimed to assess the prevalence of metabolic
      acidosis and to identify its risk factors and mechanisms. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study retrospectively analyzed 411 homozygous
      patients with SCA with a GFR >= 60 ml/min per 1.73 m(2), referred in a single
      center between 2007 and 2012. Acidosis and nonacidosis groups were compared for
      clinical and biologic data including SCA complications and hemolytic parameters.
      A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the
      setting of sickle cell-associated nephropathy, was further analyzed in order to
      better characterize metabolic acidosis. RESULTS: Metabolic acidosis was
      encountered in 42% of patients with SCA, with a higher prevalence in women (52%
      versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate
      dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02
      and P=0.03 in men and women, respectively), suggesting higher hemolytic activity
      in the former group. To note, fasting urine osmolality was low in the whole study
      population and was significantly lower in men with SCA in the acidosis group (392
      versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis
      with a normal anion gap in 14 patients, characterized by a lower urinary pH
      (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and
      aldosterone were similar between the two groups and thus could not explain
      impaired urinary ammonium excretion. CONCLUSIONS: These results suggest that the
      prevalence of metabolic acidosis in patients with SCA is underestimated and
      related to impaired ammonium availability possibly due to an altered
      corticopapillary gradient. Future studies should evaluate whether chronic
      metabolic acidosis correction may be beneficial in this population, especially in
      bone remodeling.

PMID- 24458071
TI  - Hospitalizations following living donor nephrectomy in the United States.
AB  - BACKGROUND AND OBJECTIVES: Living donors represented 43% of United States kidney
      donors in 2012. Although research suggests minimal long-term consequences of
      donation, few comprehensive longitudinal studies for this population have been
      performed. The primary aims of this study were to examine the incidence, risk
      factors, and causes of rehospitalization following donation. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: State Inpatient Databases (SID) compiled by the
      Agency for Healthcare Research and Quality were used to identify living donors in
      four different states between 2005 and 2010 (n=4524). Multivariable survival
      models were used to examine risks for rehospitalization, and patient
      characteristics were compared with data from the Scientific Registry of
      Transplant Recipients (SRTR). Outcomes among patients undergoing appendectomy
      (n=200,274), cholecystectomy (n=255,231), and nephrectomy for nonmetastatic
      carcinoma (n=1314) were contrasted. RESULTS: The study population was similar to
      United States donors (for SRTR and SID, respectively: mean age, 41 and 41 years;
      African Americans, 12% and 10%; women, 60% and 61%). The 3-year incidence of
      rehospitalization following donation was 11% for all causes and 9% excluding
      pregnancy-related hospitalizations. After censoring of models for pregnancy
      related rehospitalizations, older age (adjusted hazard ratio [AHR], 1.02 per
      year; 95% confidence interval [95% CI], 1.01 to 1.03), African American race
      (AHR, 2.16; 95% CI, 1.54 to 3.03), depression (AHR, 1.88; 95% CI, 1.12 to 3.14),
      hypothyroidism (AHR, 1.63; 95% CI, 1.06 to 2.49), and longer initial length of
      stay were related to higher rehospitalization rates among donors. Compared with
      living donors, adjusted risks for rehospitalizations were greater among patients
      undergoing appendectomy (AHR, 1.58; 95% CI, 1.42 to 1.75), cholecystectomy (AHR,
      2.25; 95% CI, 2.03 to 2.50), and nephrectomy for nonmetastatic carcinoma (AHR,
      2.95; 95% CI, 2.58 to 3.37). Risks for rehospitalizations were higher among
      African Americans than whites in each of the surgical groups. CONCLUSIONS: The
      SID is a valuable source for evaluating characteristics and outcomes of living
      kidney donors that are not available in traditional transplant databases.
      Rehospitalizations following donor nephrectomy are less than seen with other
      comparable surgical procedures but are relatively higher among donors who are
      older, are African American, and have select comorbid conditions. The increased
      risks for rehospitalizations among African Americans are not unique to living
      donation.

PMID- 24458072
TI  - Progressive inflammation and wasting in patients with ESRD.

PMID- 24458073
TI  - Race, ethnicity, and state-by-state geographic variation in hemorrhagic stroke in
      dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Geographic variation in stroke rates is well
      established in the general population, with higher rates in the South than in
      other areas of the United States. A similar pattern of geographic variation in
      ischemic strokes has also recently been reported in patients undergoing long-term
      dialysis, but whether this is also the case for hemorrhagic stroke is unknown.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medicare claims from 2000 to 2005
      were used to ascertain hemorrhagic stroke events in a large cohort of incident
      dialysis patients. A Poisson generalized linear mixed model was generated to
      determine factors associated with stroke and to ascertain state-by-state
      geographic variability in stroke rates by generating observed-to-expected (O/E)
      adjusted rate ratios (ARRs) for stroke. RESULTS: A total of 265,685 Medicare
      eligible incident dialysis patients were studied. During a median follow-up of
      15.5 months, 2397 (0.9%) patients sustained a hemorrhagic stroke. African
      Americans (ARR, 1.43; 95% confidence interval [CI], 1.30 to 1.57), Hispanics
      (ARR, 1.78; 95% CI, 1.57 to 2.03), and individuals of other races (ARR, 1.51; 95%
      CI, 1.26 to 1.80) had a significantly higher risk for hemorrhagic stroke compared
      with whites. In models adjusted for age and sex, four states had O/E ARRs for
      hemorrhagic stroke that were significantly greater than 1.0 (California, 1.15;
      Maryland, 1.25; North Carolina, 1.25; Texas, 1.19), while only 1 had an ARR less
      than 1.0 (Wisconsin, 0.79). However, after adjustment for race and ethnicity, no
      states had ARRs that varied significantly from 1.0. CONCLUSION: Race and
      ethnicity, or other factors that covary with these, appear to explain a
      substantial portion of state-by-state geographic variation in hemorrhagic stroke.
      This finding suggests that the factors underlying the high rate of hemorrhagic
      strokes in dialysis patients are likely to be system-wide and that further
      investigations into regional variations in clinical practices are unlikely to
      identify large opportunities for preventive interventions for this disorder.

PMID- 24458074
TI  - Clinical predictors of decline in nutritional parameters over time in ESRD.
AB  - BACKGROUND AND OBJECTIVES: Inflammation and malnutrition are important features
      in patients with ESRD; however, data on changes in these parameters over time are
      scarce. This study aimed to gain insight into changes over time in serum albumin,
      body mass index, high-sensitivity C-reactive protein, and IL-6 in patients with
      ESRD and aimed to identify clinical risk factors for deterioration of these
      parameters. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were analyzed
      from the Convective Transport Study, a randomized controlled trial conducted from
      June 2004 to January 2011, in which 714 patients with chronic ESRD were
      randomized to either online hemodiafiltration or low-flux hemodialysis. Albumin
      and body mass index were measured up to 6 years and predialysis C-reactive
      protein and IL-6 were measured up to 3 years in a subset of 405 participants.
      Rates of change in these parameters over time were estimated across strata of
      predefined risk factors with linear mixed-effects models. RESULTS: Albumin and
      body mass index decreased and C-reactive protein and IL-6 increased over time.
      For every incremental year of age at baseline, the yearly excess decline in
      albumin was 0.003 g/dl (-0.004 to -0.002; P<0.001) and the excess decline in body
      mass index was 0.02 kg/m(2) per year (-0.02 to -0.01; P<0.001). In patients with
      diabetes mellitus, there was a yearly excess decline of 0.05 g/dl in albumin (
      0.09 to -0.02; P=0.002). Compared with women, men had an excess decline of 0.03
      g/dl per year in albumin (-0.06 to -0.001; P=0.05) and an excess increase of
      11.6% per year in IL-6 (0.63%-23.6%; P=0.04). CONCLUSIONS: Despite guideline
      based care, all inflammatory and nutritional parameters worsened over time. The
      deterioration of some of these parameters was more pronounced in men, older
      patients, and patients with diabetes mellitus. Special focus on the nutritional
      status of at-risk patients by individualizing medical care might improve their
      prognosis.

PMID- 24458075
TI  - Performance and limitations of administrative data in the identification of AKI.
AB  - BACKGROUND AND OBJECTIVES: Billing codes are frequently used to identify AKI
      events in epidemiologic research. The goals of this study were to validate
      billing code-identified AKI against the current AKI consensus definition and to
      ascertain whether sensitivity and specificity vary by patient characteristic or
      over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population
      included 10,056 Atherosclerosis Risk in Communities study participants
      hospitalized between 1996 and 2008. Billing code-identified AKI was compared with
      the 2012 Kidney Disease Improving Global Outcomes (KDIGO) creatinine-based
      criteria (AKIcr) and an approximation of the 2012 KDIGO creatinine- and urine
      output-based criteria (AKIcr_uop) in a subset with available outpatient data.
      Sensitivity and specificity of billing code-identified AKI were evaluated over
      time and according to patient age, race, sex, diabetes status, and CKD status in
      546 charts selected for review, with estimates adjusted for sampling technique.
      RESULTS: A total of 34,179 hospitalizations were identified; 1353 had a billing
      code for AKI. The sensitivity of billing code-identified AKI was 17.2% (95%
      confidence interval [95% CI], 13.2% to 21.2%) compared with AKIcr (n=1970
      hospitalizations) and 11.7% (95% CI, 8.8% to 14.5%) compared with AKIcr_uop
      (n=1839 hospitalizations). Specificity was >98% in both cases. Sensitivity was
      significantly higher in the more recent time period (2002-2008) and among
      participants aged 65 years and older. Billing code-identified AKI captured a more
      severe spectrum of disease than did AKIcr and AKIcr_uop, with a larger proportion
      of patients with stage 3 AKI (34.9%, 19.7%, and 11.5%, respectively) and higher
      in-hospital mortality (41.2%, 18.7%, and 12.8%, respectively). CONCLUSIONS: The
      use of billing codes to identify AKI has low sensitivity compared with the
      current KDIGO consensus definition, especially when the urine output criterion is
      included, and results in the identification of a more severe phenotype.
      Epidemiologic studies using billing codes may benefit from a high specificity,
      but the variation in sensitivity may result in bias, particularly when trends
      over time are the outcome of interest.

PMID- 24458077
TI  - Association of systemic lupus erythematosus susceptibility genes with IgA
      nephropathy in a Chinese cohort.
AB  - BACKGROUND AND OBJECTIVES: One hypothesis states that IgA nephropathy (IgAN) is a
      syndrome with an autoimmune component. Recent studies strongly support the notion
      of shared genetics between immune-related diseases. This study investigated
      single-nucleotide polymorphisms (SNPs) reported to be associated with systemic
      lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in
      controls. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated
      whether SNP markers that had been reported to be associated with SLE were also
      associated with IgAN in a Chinese population. The study cohort consisted of 1194
      patients with IgAN and 902 controls enrolled in Peking University First Hospital
      from 1997 to 2008. RESULTS: Ninety-six SNPs mapping to 60 SLE loci with reported
      P values <1 * 10(-5) were investigated. CFH (P=8.41 * 10(-6)), HLA-DRA (P=4.91 *
      10(-6)), HLA-DRB1 (P=9.46 * 10(-9)), PXK (P=3.62 * 10(-4)), BLK (P=9.32 * 10(
      3)), and UBE2L3 (P=4.07 * 10(-3)) were identified as shared genes between IgAN
      and SLE. All associations reported herein were corroborated by associations at
      neighboring SNPs. Many of the alleles that are risk alleles for SLE are
      protective alleles for IgAN. By analyses of two open independent expression
      quantitative trait loci (eQTL) databases, correlations between genotypes and
      corresponding gene expression were observed (P<0.05 in multiple populations),
      suggesting a cis-eQTL effect. From gene-expression databases, differential
      expressions of these genes were observed in IgAN. Additive interactions between
      PXK rs6445961 and HLA-DRA rs9501626 (P=1.51 * 10(-2)), as well as multiplicative
      interactions between CFH rs6677604 and HLA-DRB1 rs9271366 (P=1.77 * 10(-2)), and
      between HLA-DRA rs9501626 and HLA-DRB1 rs9271366 (P=3.23 * 10(-2)) were observed.
      Disease risk decreased with accumulation of protective alleles. Network analyses
      highlighted four pathways: MHC class II antigen presentation, complement
      regulation, signaling by the B-cell receptor, and ubiquitin/proteasome-dependent
      degradation. CONCLUSION: From this "systems genetics" perspective, these data
      provide important clues for future studies on pleiotropy in IgAN and lupus
      nephritis.

PMID- 24458078
TI  - A randomized comparison of ferumoxytol and iron sucrose for treating iron
      deficiency anemia in patients with CKD.
AB  - BACKGROUND AND OBJECTIVES: Few randomized controlled trials have compared
      intravenous iron products head to head in CKD patients with iron deficiency
      anemia. This study compared the efficacy and safety of two intravenous iron
      products (ferumoxytol [Feraheme injection] and iron sucrose [Venofer]) in
      patients with CKD and iron deficiency anemia. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In this phase II, randomized, open-label, active-controlled,
      multicenter clinical trial, patients were randomized 1:1 to either 1.02 g
      ferumoxytol (2 * 510-mg injections) or 1.0 g iron sucrose administered as either
      a slow injection or infusion (10 doses for dialysis patients and 5 doses for
      nondialysis patients). Inclusion criteria included hemoglobin<11.0 g/dl,
      transferrin saturation<30%, and eGFR<60 ml/min per 1.73 m(2) or a diagnosis of
      underlying CKD (e.g., nephropathy or nephritis). The primary end point was change
      in hemoglobin from baseline to week 5. RESULTS: In total, 162 patients were
      randomized. Demographics were balanced between the treatment groups. Adverse
      event profiles of the two regimens were fairly similar: overall adverse events,
      48% ferumoxytol versus 65% iron sucrose; related adverse events, 10% ferumoxytol
      versus 16% iron sucrose; and adverse events leading to study discontinuation, 1%
      ferumoxytol versus 5% iron sucrose. Rates of serious adverse events and related
      serious adverse events were similar between the ferumoxytol and iron sucrose
      groups: serious adverse events, 9% versus 7%, respectively and related serious
      adverse events, 1% versus 1%, respectively. Overall, increases in hemoglobin were
      similar between treatment groups. Based on an ANOVA model adjusted for baseline
      hemoglobin level and dialysis status, the least squares mean change from baseline
      to week 5 was 0.8 +/- 0.1 g/dl in the ferumoxytol-treated group and 0.7 +/- 0.1
      g/dl in the iron sucrose group. The difference in the mean change from baseline
      between the two treatment groups was 0.1 g/dl (95% confidence interval, -0.2 to
      0.4). CONCLUSION: In this randomized, controlled trial, ferumoxytol and iron
      sucrose showed comparable efficacy and adverse events rates.

PMID- 24458076
TI  - Biomarkers of vascular calcification and mortality in patients with ESRD.
AB  - BACKGROUND: Vascular calcification is common among patients undergoing dialysis
      and is associated with mortality. Factors such as osteoprotegerin (OPG),
      osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved
      in vascular calcification. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: OPG,
      OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident
      dialysis patients recruited from United States dialysis centers between 1995 and
      1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their
      association with all-cause and cardiovascular mortality were assessed using Cox
      proportional hazards models adjusted for demographic characteristics,
      comorbidity, serum phosphate, and calcium. An interaction with diabetes was
      tested because of its known association with vascular calcification. Predictive
      accuracy of selected biomarkers was explored by C-statistics in nested models
      with training and validation subcohorts. RESULTS: Higher OPG and lower fetuin-A
      levels were associated with higher mortality over up to 13 years of follow-up
      (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest
      tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and
      0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest
      tertile of OPG was associated with higher mortality among patients without
      diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR,
      1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular
      mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L:
      95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated
      with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to
      7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not
      independently associated with outcomes overall. The addition of OPG and fetuin-A
      did not significantly improve predictive accuracy of mortality. CONCLUSIONS: OPG
      and fetuin-A may be risk factors for all-cause and cardiovascular mortality in
      patients undergoing dialysis, but do not improve risk prediction.

PMID- 24458079
TI  - Prevalence, awareness, and management of CKD and cardiovascular risk factors in
      publicly funded health care.
AB  - BACKGROUND AND OBJECTIVES: It is uncertain how many patients with CKD and
      cardiovascular risk factors in publicly funded universal health care systems are
      aware of their disease and how to achieve their treatment targets. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: The CARTaGENE study evaluated BP, lipid,
      and diabetes profiles as well as corresponding treatments in 20,004 random
      individuals between 40 and 69 years of age. Participants had free access to
      health care and were recruited from four regions within the province of Quebec,
      Canada in 2009 and 2010. RESULTS: CKD (Chronic Kidney Disease Epidemiology
      Collaboration equation; <60 ml/min per 1.73 m(2)) was present in 4.0% of the
      respondents, and hypertension, diabetes, and hypercholesterolemia were reported
      by 25%, 7.4%, and 28% of participants, respectively. Self-awareness was low: 8%
      for CKD, 73% for diabetes, and 45% for hypercholesterolemia. Overall, 31% of
      patients with hypertension did not meet BP goals, and many received fewer
      antihypertensive drugs than appropriately controlled individuals; 41% of patients
      with diabetes failed to meet treatment targets. Among those patients with a
      moderate or high Framingham risk score, 53% of patients had LDL levels above the
      recommended levels, and many patients were not receiving a statin. Physician
      checkups were not associated with greater awareness but did increase the
      achievement of targets. CONCLUSION: In this population with access to publicly
      funded health care, CKD and cardiovascular risk factors are common, and self
      awareness of these conditions is low. Recommended targets were frequently not
      achieved, and treatments were less intensive in those patients who failed to
      reach goals. New strategies to enhance public awareness and reach guideline
      targets should be developed.

PMID- 24458080
TI  - Metabolic syndrome in peritoneal dialysis patients: choice of diagnostic criteria
      and prognostic implications.
AB  - BACKGROUND AND OBJECTIVE: In the general population, metabolic syndrome (MES) is
      associated with cardiovascular risk. However, the definition of MES and its
      prognostic implication among patients undergoing peritoneal dialysis (PD) remain
      controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 329
      prevalent PD patients from April 2008 to April 2011 and compared four sets of
      diagnostic criteria: the original World Health Organization (WHO) criteria, the
      International Diabetes Federation (IDF) criteria, the original National
      Cholesterol Education Program (NCEP) criteria, and the modified NCEP criteria.
      Nutritional status, body composition, and arterial pulse-wave velocity were
      measured. Patients were followed for 31.7 +/- 15.5 months. RESULTS: Among the 329
      patients, 175 (53.2%) fulfilled the WHO criteria, 177 (53.8%) the IDF criteria,
      199 (60.5%) the original NCEP criteria, and 218 (66.3%) the modified NCEP
      criteria. The agreement among the four sets of criteria was fair to moderate
      (Cohen kappa=0.35-0.58). Patients with MES defined by all four criteria had
      higher adipose tissue mass than the others, although the difference in adipose
      tissue mass was most pronounced with the IDF criteria (MES versus no MES, 18.2 +/
      7.9 versus 10.7 +/- 5.9 kg; P<0.001). Patients with MES, as defined by the IDF
      criteria, were hospitalized longer than those without MES (3.82 [interquartile
      range, 0.00-12.61] versus 1.07 [interquartile range, 0.00-6.43]) days per year of
      follow-up; P=0.01). Overall survival, cardiovascular survival, or technique
      survival did not differ between patients with and without MES, irrespective of
      the diagnostic criteria after adjustment for diabetic status. CONCLUSION: In
      patients undergoing PD, overall survival, cardiovascular survival, and technique
      survival did not differ between patients with and without MES, irrespective of
      diabetic status and diagnostic criteria. Further studies are needed to establish
      a new definition or clinical scoring system for risk stratification of PD
      patients.

PMID- 24458081
TI  - Alkaline phosphatase and mortality in patients on peritoneal dialysis.
AB  - BACKGROUND AND OBJECTIVES: Elevated total serum alkaline phosphatase levels have
      been associated with higher mortality in the general population, CKD patients,
      and hemodialysis patients. However, in peritoneal dialysis patients, this
      association has received little attention. The aim of this study was to evaluate
      the association between alkaline phosphatase and all-cause and cardiovascular
      mortality in peritoneal dialysis patients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In this single center retrospective cohort study, 1021 incident
      peritoneal dialysis patients from January 1, 2006, to December 31, 2010 with
      baseline serum alkaline phosphatase values were enrolled. Collected baseline data
      included demographic characteristics and clinical and laboratory measurements.
      All patients were followed until December 31, 2012. The associations of total
      serum alkaline phosphatase levels with all-cause and cardiovascular mortality
      were assessed using multivariable-adjusted Cox models. RESULTS: Of 1021 patients,
      mean age was 47.5 (+/- 15.5) years, 59.1% of patients were men, and 22.8% of
      patients were diabetic. The median serum alkaline phosphatase level was 64 U/L
      (interquartile range=52-82 U/L). During a median 31-month (interquartile range=19
      45 months) follow-up period, 203 patients died, of which 109 deaths were caused
      by cardiovascular disease. After adjusting for demographics, comorbid conditions,
      liver function, and bone metabolism parameters, the highest alkaline phosphatase
      quartile was significantly associated with a hazard ratio for all-cause mortality
      of 1.70 (95% confidence interval, 1.06 to 2.74, P=0.03) and a hazard ratio for
      cardiovascular mortality of 1.94 (95% confidence interval, 1.02 to 3.72, P=0.04).
      Each 10 U/L higher baseline alkaline phosphatase level was associated with 4%
      (95% confidence interval, 1.00 to 1.08, P=0.04) and 7% (95% confidence interval,
      1.02 to 1.11, P=0.003) higher risk of all-cause and cardiovascular mortality,
      respectively. CONCLUSION: Higher total serum alkaline phosphatase levels at the
      commencement of peritoneal dialysis were independently associated with all-cause
      and cardiovascular mortality in peritoneal dialysis patients.

PMID- 24458082
TI  - Renal relevant radiology: use of ultrasound in kidney disease and nephrology
      procedures.
AB  - Ultrasound is commonly used in nephrology for diagnostic studies of the kidneys
      and lower urinary tract and to guide percutaneous procedures, such as insertion
      of hemodialysis catheters and kidney biopsy. Nephrologists must, therefore, have
      a thorough understanding of renal anatomy and the sonographic appearance of
      normal kidneys and lower urinary tract, and they must be able to recognize common
      abnormalities. Proper interpretation requires correlation with the clinical
      scenario. With the advent of affordable, portable scanners, sonography has become
      a procedure that can be performed by nephrologists, and both training and
      certification in renal ultrasonography are available. 

PMID- 24458083
TI  - Rehospitalization after living kidney donation.

PMID- 24458085
TI  - Dialysis therapies: a National Dialogue.
AB  - The National Institute of Diabetes, Digestive, and Kidney Diseases-supported
      Kidney Research National Dialogue asked the scientific community to formulate and
      prioritize research objectives that would improve our understanding of kidney
      function and disease. Kidney Research National Dialogue participants identified
      the need to improve outcomes in ESRD by decreasing mortality and morbidity and
      enhancing quality of life as high priority areas in kidney research. To reach
      these goals, we must identify retained toxins in kidney disease, accelerate
      technologic advances in dialysate composition and devices to remove these toxins,
      advance vascular access, and identify measures that decrease the burden of
      disease in maintenance dialysis patients. Together, these research objectives
      provide a path forward for improving patient-centered outcomes in ESRD. 

PMID- 24458084
TI  - Association of kidney function with changes in the endothelial surface layer.
AB  - BACKGROUND AND OBJECTIVES: ESRD is accompanied by endothelial dysfunction.
      Because the endothelial glycocalyx (endothelial surface layer) governs
      interactions between flowing blood and the vessel wall, perturbation could
      influence disease progression. This study used a novel noninvasive sidestream
      darkfield imaging method, which measures the accessibility of red blood cells to
      the endothelial surface layer in the microcirculation (perfused boundary region),
      to investigate whether renal function is associated with endothelial surface
      layer dimensions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Perfused
      boundary region was measured in control participants (n=10), patients with ESRD
      (n=23), participants with normal kidney function after successful living donor
      kidney transplantation (n=12), and patients who developed interstitial
      fibrosis/tubular atrophy after kidney transplantation (n=10). In addition, the
      endothelial activation marker angiopoietin-2 and shed endothelial surface layer
      components syndecan-1 and soluble thrombomodulin were measured using ELISA.
      RESULTS: Compared with healthy controls (1.82 +/- 0.16 um), ESRD patients had a
      larger perfused boundary region (+0.23; 95% confidence interval, 0.46 to <0.01;
      P<0.05), which signifies loss of endothelial surface layer dimensions. This large
      perfused boundary region was accompanied by higher circulating levels of syndecan
      1 (+57.71; 95% confidence interval, 17.38 to 98.04; P<0.01) and soluble
      thrombomodulin (+12.88; 95% confidence interval, 0.29 to 25.46; P<0.001). After
      successful transplantation, the perfused boundary region was indistinguishable
      from healthy controls (without elevated levels of soluble thrombomodulin or
      syndecan-1). In contrast, however, patients who developed interstitial fibrosis
      and tubular atrophy showed a large perfused boundary region (+0.36; 95%
      confidence interval, 0.09 to 0.63; P<0.01) and higher levels of endothelial
      activation markers. In addition, a significant correlation between perfused
      boundary region, angiopoietin-2, and eGFR was observed (perfused boundary region
      versus GFR: Spearman's rho=0.31; P<0.05; perfused boundary region versus
      angiopoietin-2: Spearman's rho=-0.33; P<0.05). CONCLUSION: Reduced renal function
      is strongly associated with low endothelial surface layer dimensions. After
      successful kidney transplantation, the endothelial surface layer is
      indistinguishable from control.

PMID- 24458087
TI  - A comparison of vaginal surgery and operative hysteroscopy for the treatment of
      cesarean-induced isthmocele: a retrospective review.
AB  - BACKGROUND/AIMS: Cesarean-induced isthmocele can cause heavy or prolonged menses,
      dyspareunia, and dysmenorrhea. We compared the efficacy of vaginal surgery and
      operative hysteroscopy for the treatment of cesarean-induced isthmocele. METHODS:
      Seventy-seven women with cesarean-induced isthmocele underwent either vaginal
      surgery or operative hysteroscopy between August 2008 and December 2011. We
      evaluated operating time, blood loss, complications, and postoperative pregnancy.
      Operative efficacy was defined as an improvement in menstrual periods and a
      change in residual isthmocele nidus size on transvaginal ultrasonography.
      RESULTS: The operative efficacy of vaginal surgery was superior to that of
      hysteroscopy (93.5 vs. 64.5%; p < 0.001). However, patients who underwent vaginal
      surgery had a longer operative time (55 vs. 25 min; p < 0.001) and greater blood
      loss (50 vs. 10 ml; p < 0.001). Two patients in each group were able to achieve
      subsequent pregnancy. Patients who had menstrual periods longer than 7 days after
      surgery were more likely to have a residual nidus. CONCLUSIONS: The therapeutic
      efficacy of vaginal surgery is superior to operative hysteroscopy in the
      treatment of cesarean-induced isthmocele.

PMID- 24458088
TI  - Si photoanode protected by a metal modified ITO layer with ultrathin NiO(x) for
      solar water oxidation.
AB  - We report an ultrathin NiOx catalyzed Si np(+) junction photoanode for a stable
      and efficient solar driven oxygen evolution reaction (OER) in water. A stable
      semi-transparent ITO/Au/ITO hole conducting oxide layer, sandwiched between the
      OER catalyst and the Si photoanode, is used to protect the Si from corrosion in
      an alkaline working environment, enhance the hole transportation, and provide a
      pre-activation contact to the NiOx catalyst. The NiOx catalyzed Si photoanode
      generates a photocurrent of 1.98 mA cm(-2) at the equilibrium water oxidation
      potential (EOER = 0.415 V vs. NHE in 1 M NaOH solution). A thermodynamic solar-to
      oxygen conversion efficiency (SOCE) of 0.07% under 0.51-sun illumination is
      observed. The successful development of a low cost, highly efficient, and stable
      photoelectrochemical electrode based on earth abundant elements is essential for
      the realization of a large-scale practical solar fuel conversion. 

PMID- 24458086
TI  - A predictive model of progression of CKD to ESRD in a predialysis pediatric
      interdisciplinary program.
AB  - BACKGROUND AND OBJECTIVES: The incidence of ESRD in children has increased over
      the last two decades. Nevertheless, there are still limited data on risk factors
      related to the emergence of ESRD among patients with CKD. The aim of this study
      was to develop a model of prediction of ESRD in children and adolescents with CKD
      (stages 2-4) enrolled in a predialysis interdisciplinary management program.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective cohort
      study, 147 patients with CKD admitted from 1990 to 2008 were systematically
      followed up at a tertiary pediatric nephrology unit for a median of about 4.5
      years. The primary outcome was the progression to CKD stage 5. A predictive model
      was developed using Cox proportional hazards model and evaluated by c statistics.
      RESULTS: The median renal survival was estimated at 98.7 months (95% confidence
      interval [95% CI], 68.7 to 129.6 months). The probability of reaching CKD stage 5
      was estimated as 52% in 10 years. The most accurate model included eGFR,
      proteinuria at admission, and primary renal disease. Risk score ranged from 0 to
      13 points (median, 4 points). The accuracy of the score applied to the sample was
      high, with c statistics of 0.865 (95% CI, 0.80 to 0.93) and 0.837 (95% CI, 0.76
      to 0.91) at follow-up of 2 and 5 years, respectively. By survival analysis, it
      was estimated that at 10 years after admission, the probability of renal survival
      was about 63% for patients in the low-risk group and 43% for the medium-risk
      group; all patients assigned to the high-risk group had CKD stage 5 (P<0.001).
      CONCLUSION: The predictive model of progression of CKD might contribute to early
      identification of a subgroup of patients at high risk for accelerated renal
      failure.

PMID- 24458090
TI  - Photodegradation routes of the herbicide bromoxynil in solution and sorbed on
      silica nanoparticles.
AB  - Some organic contaminants dissolved in natural waters tend to adsorb on suspended
      particles and sediments. In order to mimic the photodegradation routes in natural
      waters of bromoxynil (BXN) adsorbed on silica, we here prepare and characterize
      silica nanoparticles modified with BXN (NP-BXN). We measure the direct photolysis
      quantum yield of aqueous BXN at 307 nm (0.064 +/- 0.001) and detect the formation
      of bromide ions as a reaction product. Under similar conditions the photolysis
      quantum yield of BXN bonded to NP-BXN is much lower (0.0021 +/- 0.0004) and does
      not lead to formation of bromide ions. The rate constant of the reaction of NP
      BXN with the excited triplet states of riboflavin, a molecule employed as a proxy
      of chromophore dissolved organic matter (DOM) was measured in laser flash
      photolysis experiments. The rate constants for the overall (kt) and chemical
      interaction (kr) of singlet oxygen with NP-BXN were also measured. Kinetic
      computer simulations show that the relevance of the direct and indirect (through
      reactions with reactive species generated in photoinduced processes)
      photodegradation routes of BXN is very much affected by sorption on silica.
      Immobilization of the herbicide on the particles, on one hand, affects the
      photolysis mechanism and lowers its photolysis quantum yield. On the other hand,
      the results obtained in aqueous suspensions indicate that immobilization also
      lowers the rate of collisional encounter, which affects the quenching rate
      constants of excited triplet states and singlet oxygen with the herbicide. 

PMID- 24458089
TI  - Rapid immunoglobulin M-based dengue diagnostic test using surface plasmon
      resonance biosensor.
AB  - Surface plasmon resonance (SPR) is a medical diagnosis technique with high
      sensitivity and specificity. In this research, a new method based on SPR is
      proposed for rapid, 10-minute detection of the anti-dengue virus in human serum
      samples. This novel technique, known as rapid immunoglobulin M (IgM)-based dengue
      diagnostic test, can be utilized quickly and easily at the point of care. Four
      dengue virus serotypes were used as ligands on a biochip. According to the
      results, a serum volume of only 1 MUl from a dengue patient (as a minimized
      volume) is required to indicate SPR angle variation to determine the ratio of
      each dengue serotype in samples with 83-93% sensitivity and 100% specificity.

PMID- 24458091
TI  - Effectiveness of efavirenz compared with ritonavir-boosted protease-inhibitor
      based regimens as initial therapy for patients with plasma HIV-1 RNA above
      100,000 copies/ml.
AB  - BACKGROUND: There are no clinical trials in which the main objective is to
      compare the efficacy of efavirenz versus ritonavir-boosted protease inhibitor
      (PI/r)-based initial antiretroviral therapy (ART) in patients with high plasma
      HIV-1 RNA levels. This study aims to compare these regimens in this patient
      population in the setting of routine clinical practice. METHODS: This was a
      multicentre, observational cohort study, including 596 consecutive treatment
      naive patients with plasma HIV-1 RNA>100,000 copies/ml initiating efavirenz or
      PI/r-based ART between 2000 and 2010. The primary effectiveness end point was the
      percentage of patients with HIV-1 RNA<50 copies/ml at week 48 by intent-to-treat
      analysis. RESULTS: Among a total of 596 patients, 57% initiated efavirenz and 43%
      PI/r-regimens (73% lopinavir and fosamprenavir [62% lopinavir, 11%
      fosamprenavir]). HIV-1 RNA suppression to <50 copies/ml at week 48 was higher in
      the efavirenz group (84% versus 74% [difference 10%, 95% CI 3.4%, 16.7%;
      P=0.002]). The percentage of virological failures was similar (efavirenz 4%
      versus PI/r 4%; P=0.686), but voluntary discontinuations and toxicity-related
      treatment changes were higher with PI/r (4% versus 1%; P=0.006 and 11% versus 6%;
      P=0.069, respectively). However, resistance selection at failure was higher in
      patients receiving efavirenz (89% versus 50%; P=0.203). Efavirenz was
      significantly more effective than lopinavir/r or fosamprenavir/r, whereas no
      significant differences were observed between efavirenz and darunavir/r or
      atazanavir/r. The high viral suppression in the efavirenz group was also evident
      in patients with very high viral loads (>500,000 copies/ml) and in those with low
      CD4(+) T-cell counts. CONCLUSIONS: In routine clinical practice, the
      effectiveness of initial efavirenz-based regimens was at least similar to or even
      higher than various PI/r-based regimens in HIV-1-infected patients with plasma
      HIV-1 RNA>100,000 copies/ml.

PMID- 24458092
TI  - Paricalcitol ameliorates epithelial-to-mesenchymal transition in the peritoneal
      mesothelium.
AB  - BACKGROUND: The purpose of the present study was to examine the effectiveness of
      paricalcitol for the prevention of epithelial-to-mesenchymal transition (EMT).
      MATERIALS AND METHODS: Human peritoneal mesothelial cells (HPMCs) were cultured
      in media containing transforming growth factor beta1 (TGF-beta1) with or without
      paricalcitol. Forty-two male Sprague-Dawley rats were divided into three groups.
      In the control group, the catheter was inserted but no dialysate was infused. The
      peritoneal dialysis (PD) group was infused with a conventional 4.25% dialysis
      solution. The paricalcitol group was infused with 4.25% dialysis solution and
      cotreated with paricalcitol. RESULTS: Exposure of HPMCs to TGF-beta1 decreased
      the protein level of the epithelial cell marker and increased the expression
      levels of the mesenchymal markers. Cotreatment with paricalcitol increased the
      protein levels of the epithelial cell marker and decreased those of mesenchymal
      markers compared with their levels in cells treated with TGF-beta1 alone.
      Exposure of HPMCs to TGF-beta1 significantly increased the phosphorylation of
      Smad2 and Smad3. Cotreatment with paricalcitol significantly decreased the
      phosphorylation of Smad2 and Smad3 compared with that of cells treated with TGF
      beta1 alone. After 8 weeks of experimental PD in rats, the thickness of the
      peritoneal membrane in the PD group was significantly increased compared with
      that of the control group. Cotreatment with paricalcitol decreased peritoneal
      thickness. CONCLUSION: The present study showed that paricalcitol attenuates the
      TGF-beta1-induced EMT in peritoneal mesothelial cells. We suggest that
      paricalcitol may preserve peritoneal mesothelial cells during PD and could thus
      be of value for the success of long-term PD.

PMID- 24458093
TI  - Cooperative effects of solvent and polymer acceptor co-additives in P3HT:PDI
      solar cells: simultaneous optimization in lateral and vertical phase separation.
AB  - In this work, solvent chloronaphthalene (CN) and polymer acceptor an alternating
      copolymer of perylene diimide and carbazole (PCPDI) were utilized as co-additives
      to optimize the nanoscale phase-separated morphology and photovoltaic properties
      of bulk-heterojunction (BHJ) polymer solar cells based on the poly(3-hexyl
      thiophene) (P3HT)/N,N'-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic
      diimide (EP-PDI) system. The domain size of EP-PDI molecules together with that
      of P3HT distinctly decreased by adding a 0.75 vol% CN additive. The optimized
      lateral phase separation increased the donor-acceptor interfacial area and
      facilitated the exciton dissociation process, leading to 5-fold enhancement of
      short-circuit current (JSC). Furthermore, when PCPDI was employed as a co
      additive, acceptor materials (including PCPDI and EP-PDI) were prone to
      aggregation towards the top surface of blend films, improving vertical phase
      separation of active layers. PCPDI incorporation, which improved the percolation
      pathways for electron carriers, suppressed the crystallinity of P3HT distinctly.
      Thus, much more balanced charge transport was achieved by PCPDI addition, which
      resulted in almost 1-fold enhancement of open-circuit voltage (VOC) by reducing
      nongeminate recombination. As a consequence, cooperative effects of CN and PCPDI
      additives improved the nanoscale phase-separated morphology in lateral and
      vertical directions simultaneously, achieving the enhancement in both VOC and
      JSC. 

PMID- 24458095
TI  - Diabetic neuropathies: diagnosis and management.
AB  - INTRODUCTION: Changes in human behaviour and lifestyle over the last century have
      resulted in a dramatic increase in the incidence of diabetes worldwide.
      Neuropathy is a common and costly complication of both type 1 and type 2
      diabetes. The prevalence of neuropathy is estimated to be about 8% in newly
      diagnosed patients and greater than 50% in patients with long-standing disease.
      There are two main types of diabetic neuropathies, named as sensorimotor and
      autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia
      and sensory loss, and autonomic neuropathy may contribute to myocardial
      infarction, malignant arrhythmia and sudden death. METHODS: In this article we
      reviewed the pathogenesis, clinical manifestations diagnosis and treatment of
      diabetic neuropathies. CONCLUSION: Sensorimotor and autonomic neuropathies
      (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are
      common in diabetic patients. Apart from strict glycaemic control, no further
      therapeutic approach exists in the prevention of this phenomenon. Intensive
      diabetes therapy, intensive multifactorial cardiovascular risk reduction and
      lifestyle intervention are recommended in patients with cardiovascular autonomic
      neuropathy. Gastroparesis is the most debilitating complication of
      gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can
      cause sexual dysfunction and neurogenic bladder; these conditions are hard to
      manage. The symptomatic treatment of sensory symptoms includes tricyclic
      antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin,
      pregabalin and opioids. Other treatment strategies are not so effective.

PMID- 24458094
TI  - VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating
      the YAP-TEAD transcriptional complex.
AB  - Lung cancer is one of the most devastating diseases worldwide with high incidence
      and mortality. Hippo (Hpo) pathway is a conserved regulator of organ size in both
      Drosophila and mammals. Emerging evidence has suggested the significance of Hpo
      pathway in cancer development. In this study, we identify VGLL4 as a novel tumor
      suppressor in lung carcinogenesis through negatively regulating the formation of
      YAP-TEAD complex, the core component of Hpo pathway. Our data show that VGLL4 is
      frequently observed to be lowly expressed in both mouse and human lung cancer
      specimens. Ectopic expression of VGLL4 significantly suppresses the growth of
      lung cancer cells in vitro. More importantly, VGLL4 significantly inhibits lung
      cancer progression in de novo mouse model. We further find that VGLL4 inhibits
      the activity of the YAP-TEAD transcriptional complex. Our data show that VGLL4
      directly competes with YAP in binding to TEADs and executes its growth-inhibitory
      function through two TDU domains. Collectively, our study demonstrates that VGLL4
      is a novel tumor suppressor for lung cancer through negatively regulating the YAP
      TEAD complex formation and thus the Hpo pathway. 

PMID- 24458096
TI  - A sequence-specific DNA glycosylase mediates restriction-modification in
      Pyrococcus abyssi.
AB  - Restriction-modification systems consist of genes that encode a restriction
      enzyme and a cognate methyltransferase. Thus far, it was believed that
      restriction enzymes are sequence-specific endonucleases that introduce double
      strand breaks at specific sites by catalysing the cleavages of phosphodiester
      bonds. Here we report that based on the crystal structure and enzymatic activity,
      one of the restriction enzymes, R.PabI, is not an endonuclease but a sequence
      specific adenine DNA glycosylase. The structure of the R.PabI-DNA complex shows
      that R.PabI unwinds DNA at a 5'-GTAC-3' site and flips the guanine and adenine
      bases out of the DNA helix to recognize the sequence. R.PabI catalyses the
      hydrolysis of the N-glycosidic bond between the adenine base and the sugar in the
      DNA and produces two opposing apurinic/apyrimidinic (AP) sites. The opposing AP
      sites are cleaved by heat-promoted beta elimination and/or by endogenous AP
      endonucleases of host cells to introduce a double-strand break. 

PMID- 24458097
TI  - Eye care availability and access among individuals with diabetes, diabetic
      retinopathy, or age-related macular degeneration.
AB  - IMPORTANCE Understanding whether differences in the local availability of eye
      care professionals are related to differences in realized access to eye care is
      important for assessing whether and where public health efforts are needed to
      increase access to eye care professionals. OBJECTIVE To examine whether the
      county-level availability of ophthalmologists and optometrists is associated with
      measures of realized access to eye care for individuals with diabetes mellitus,
      diabetic retinopathy, or age-related macular degeneration (ARMD). DESIGN,
      SETTING, AND PARTICIPANTS We studied a cross-sectional sample of US adults 40
      years and older (1098 individuals with diabetes, 345 with diabetic retinopathy,
      and 498 with ARMD) from the 2005-2008 National Health and Nutrition Examination
      Survey. MAIN OUTCOMES AND MEASURES Outcomes were whether diabetic individuals
      reported undergoing a dilated eye examination in the past year, whether
      individuals were unaware they had diabetic retinopathy, whether diabetic
      individuals had vision-threatening diabetic retinopathy, and whether individuals
      were unaware they had ARMD. RESULTS In logistic regression models that also
      included individual characteristics, individuals who lived in a county in the
      highest ophthalmologist availability quartile were less likely to be unaware they
      had diabetic retinopathy (predictive margin [PM], 66.1%; 90% CI, 48.8%-83.4%; vs
      PM, 84.1%; 90% CI, 78.7%-89.6%) and were less likely to have vision-threatening
      diabetic retinopathy (PM, 1.4%; 90% CI, 0.9%-1.9%; vs PM, 2.6%; 90% CI, 1.8%
      3.4%) than individuals who lived in a county in the lower 3 ophthalmologist
      availability quartiles. Individuals who lived in a county in the lowest
      ophthalmologist availability quartile were more likely to be unaware they had
      ARMD (PM, 93.8%; 90% CI, 90.6%-97.0%; vs PM, 88.3%; 90% CI, 84.7%-91.9%) than
      individuals who lived a county in the higher 3 ophthalmologist availability
      quartiles. Optometrist availability quartiles were not significantly related to
      any of the outcomes. CONCLUSIONS AND RELEVANCE The results suggest that efforts
      to increase access to ophthalmologists to improve outcomes related to diabetic
      retinopathy or to increase awareness of ARMD should focus on improving access for
      diabetic individuals who live in counties in the lowest 3 quartiles of
      ophthalmologist availability and on individuals at risk of ARMD who live in
      counties in the lowest quartile of ophthalmologist availability. 

PMID- 24458099
TI  - Hydration and urinary pseudoephedrine levels after a simulated team game.
AB  - This study investigated the influence of dehydration on urinary levels of
      pseudoephedrine (PSE) after prolonged repeated effort activity. Fourteen athletes
      performed a simulated team game circuit (STGC) outdoors over 120 min under three
      different hydration protocols: hydrated (HYD), dehydrated (DHY) and dehydrated +
      postexercise fluid bolus (BOL). In all trials, a 60 mg dose of PSE was
      administered 30 min before trial and at half time of the STGC. Urinary PSE levels
      were measured before drug administration and at 90 min postexercise. In addition,
      body mass (BM) changes and urinary specific gravity (USG), osmolality (OSM),
      creatinine (Cr), and pH values were recorded. No differences in PSE levels were
      found 90 min postexercise between conditions (HYD: 208.5 +/- 116.5; DHY: 238.9 +/
      93.5; BOL: 195.6 +/- 107.3 MUg . ml(-1)), although large variations were seen
      within and between participants across conditions (range: 33-475 MUg . ml(-1):
      ICC r = .03-0.16, p > .05). There were no differences between conditions in USG,
      OSM, pH or PSE/Cr ratio. In conclusion, hydration status did not influence
      urinary PSE levels after prolonged repeated effort activity, with ~70% of samples
      greater than the WADA limit (>150 MUg . ml(-1)), and ~30% under. Due to the
      unpredictability of urinary PSE values, athletes should avoid taking any
      medications containing PSE during competition.

PMID- 24458100
TI  - Effect of exercise and gait retraining on knee adduction moment in people with
      knee osteoarthritis.
AB  - The knee adduction moment represents the medial knee joint load, and greater
      value is associated with higher load. In people with knee osteoarthritis, it is
      important to apply proper treatment with the least side effects to reduce knee
      adduction moment and, consequently, reduce medial knee joint load. This reduction
      may slow the progression of knee osteoarthritis. The research team performed a
      literature search of electronic databases. The search keywords were as follows:
      knee osteoarthritis, knee adduction moment, exercise program, exercise therapy,
      gait retraining, gait modification and knee joint loading. In total, 12 studies
      were selected, according to the selection criteria. Findings from previous
      studies illustrated that exercise and gait retraining programs could alter knee
      adduction moment in people with knee osteoarthritis. These treatments are
      noninvasive and nonpharmacological which so far have no or few side effects, as
      well as being low cost. The results of this review revealed that gait retraining
      programs were helpful in reducing the knee adduction moment. In contrast, not all
      the exercise programs were beneficial in reducing knee adduction moment. Future
      studies are needed to indicate best clinical exercise and gait retraining
      programs, which are most effective in reducing knee adduction moment in people
      with knee osteoarthritis. 

PMID- 24458101
TI  - Biferrocenium salts with magnetite-like mixed-valence iron: coexistence of Fe3+
      and Fe(2.5+) in the crystal.
AB  - The biferrocene-based salt [Bifc]2[Ni(mnt)2]3 (Bifc =
      bis(isopropylthio)biferrocene; mnt = maleonitriledithiolate) contains a
      biferrocenium monocation and dication within the same crystal. The coexistence of
      Fe(3+) and mixed-valence Fe(2.5+), which resembles the valence state of
      magnetite, was confirmed by Mossbauer spectroscopy. 

PMID- 24458098
TI  - Primary orthotopic glioma xenografts recapitulate infiltrative growth and
      isocitrate dehydrogenase I mutation.
AB  - Malignant gliomas constitute a heterogeneous group of highly infiltrative glial
      neoplasms with distinct clinical and molecular features. Primary orthotopic
      xenografts recapitulate the histopathological and molecular features of malignant
      glioma subtypes in preclinical animal models. To model WHO grades III and IV
      malignant gliomas in transplantation assays, human tumor cells are xenografted
      into an orthotopic site, the brain, of immunocompromised mice. In contrast to
      secondary xenografts that utilize cultured tumor cells, human glioma cells are
      dissociated from resected specimens and transplanted without prior passage in
      tissue culture to generate primary xenografts. The procedure in this report
      details tumor sample preparation, intracranial transplantation into
      immunocompromised mice, monitoring for tumor engraftment and tumor harvesting for
      subsequent passage into recipient animals or analysis. Tumor cell preparation
      requires 2 hr and surgical procedure requires 20 min/animal. 

PMID- 24458102
TI  - Tripartite conflicts of interest and high stakes patent extensions in the DSM-5.
AB  - BACKGROUND: The revision process for and recent publication of the DSM-5
      initiated debates about the widening of diagnostic boundaries. The pharmaceutical
      industry had a major financial stake in the outcome of these debates. This study
      examines the three-part relationship among DSM panel members, principal
      investigators (PIs) of clinical trials for new DSM-5 diagnoses, and drug
      companies. METHODS: Financial conflicts of interest (FCOI) of DSM panel members
      responsible for some new diagnoses in the DSM-5 and PIs of clinical trials for
      related drug treatments were identified. Trials were found by searching
      ClinicalTrials.gov. Patent and revenue information about these drugs was found
      using the US Food and Drug Administration's Orange Book and manufacturer Annual
      Reports. RESULTS: Thirteen trials met inclusion criteria (testing drugs for some
      new DSM disorders). Sixty-one percent of the DSM Task Force members and 27% of
      Work Group members reported FCOI to the trial drug manufacturers. In 5 of the 13
      trials (38%), PIs reported ties other than research funding to the drug
      manufacturer. In 3 of the trials (23%), a PI had financial ties to the drug
      manufacturer and was also a DSM panel member who had decision-making authority
      over the revision process. CONCLUSIONS: These findings suggest that increased
      transparency (e.g., registration on ClinicalTrials.gov) and mandatory disclosure
      policies (e.g., the American Psychiatric Association's disclosure policy for DSM
      5 panel members) alone may not be robust enough strategies to prevent the
      appearance of bias in both the DSM revision process as well as clinical decisions
      about appropriate interventions for DSM disorders.

PMID- 24458105
TI  - Advances in endoscopic techniques.

PMID- 24458104
TI  - Acute effects of an oral supplement of (-)-epicatechin on postprandial fat and
      carbohydrate metabolism in normal and overweight subjects.
AB  - Postprandial hyperglycemia, in particular when accompanied by excessive
      hypertriglyceridemia, is associated with increased cardiovascular risk, mainly in
      overweight or obese subjects, as it favors oxidative stress, systemic
      inflammation and endothelial dysfunction. Thus, treatments that favorably
      modulate metabolism by reducing steep increases in postprandial serum glucose and
      triglycerides, are of considerable interest. Evidence suggests that (-)
      epicatechin (EPI) is responsible for reductions in cardiometabolic risk
      associated with chocolate consumption; these effects may be associated with
      favorable effects of EPI on postprandial metabolism. The aims of this study were
      to assess the effects of EPI on postprandial metabolism in normal-weight and
      overweight/obese subjects. Twenty adult volunteers (normal and overweight)
      underwent oral metabolic tolerance tests in the absence and presence of oral EPI
      (1 mg kg(-1)). Metabolic responses were examined using indirect calorimetry and
      determining blood glucose and triglycerides at 0, 2 and 4 hours after metabolic
      load ingestion. Results show that EPI increased postprandial lipid catabolism, as
      evidenced by a significant decrease in the respiratory quotient, which implies an
      increase in fat oxidation. The effect was associated with significantly lower
      postprandial plasma glucose and triglycerides concentrations. The effects were
      more prominent in overweight subjects. In conclusion, EPI modulates postprandial
      metabolism by enhancing lipid oxidation accompanied by reductions in glycemia and
      triglyceridemia. 

PMID- 24458106
TI  - Significance of background coloration in endoscopic detection of early esophageal
      squamous cell carcinoma.
AB  - Endoscopic diagnostics of early squamous cell carcinoma (SCC) in the laryngo
      esophageal region have dramatically improved together with development of less
      invasive endoscopic treatment. It is essential for gastrointestinal endoscopists
      to detect lesions when they are still endoscopically treatable, especially in
      this region since surgical approach can still be extremely invasive. Pioneers
      have found some notable fundamental alterations in early SCC and created several
      classifications. Inoue [Dig Endosc 2001;13(suppl): 40-41] proposed the
      intrapapillary capillary (IPCL) classification, which focused on the
      microvascular change of the mucosal surface. One of the significances of this
      classification is that it clearly distinguished the lesions that require further
      pathological evaluation by categorizing the diameter change of the IPCLs. On the
      other hand, Arima et al. [Esophagus 2005;2:191-197] advocated the alteration of
      microvessels as well as change of the vascular arrangement in the area. Most
      recently, the Japan Esophageal Society constructed a new classification uniting
      these two exemplary classifications as the 'Japanese Classification of Magnifying
      Endoscopy for Early Squamous Cell Carcinoma'. This classification was intended to
      be simple and easily applicable in general clinical practice. Brownish color
      change between the IPCLs has reported to be one of the useful findings in
      distinguishing early SCC from benign changes such as inflammatory change and low
      grade intraepithelial neoplasia. Nevertheless, the exact cause of this phenomenon
      remains unclear. We recently examined the association of color change with
      hemoglobin (Hb) in cancer tissue, since NBI exclusively detects the wavelength of
      Hb in superficial vessels in the gastrointestinal tract. This review article also
      describes our examination of a distinct finding in esophageal cancer, namely,
      'background coloration'.

PMID- 24458107
TI  - HER2 expression and PI3K-Akt pathway alterations in gastric cancer.
AB  - The anti-HER2 antibody trastuzumab has led to an era of personalized therapy in
      gastric cancer (GC). As a result, HER2 expression has become a major concern in
      GC. HER2 overexpression is seen in 7-34% of GC cases. Trastuzumab is an antibody
      that targets the HER2 extracellular domain and induces antibody-dependent
      cellular cytotoxicity and inhibition of the HER2 downstream signals. Mechanisms
      of resistance to trastuzumab have been reported in breast cancer. There are
      various mechanisms underlying trastuzumab resistance, such as alterations of HER2
      structure or surroundings, dysregulation of HER2 downstream signal effectors and
      interaction of HER2 with other membrane receptors. The PI3K-Akt pathway is one of
      the main downstream signaling pathways of HER2. It is well known that PIK3CA
      mutations and phosphate and tensin homolog (PTEN) inactivation cause over
      activation of the downstream signal without an upstream signal activation.
      Frequencies of PIK3CA mutations and PTEN inactivation have been reported to be 4
      25 and 16-77%, respectively. However, little is known about the association
      between HER2 expression and PI3K-Akt pathway alterations in GC. We have found
      that HER2 over-expression was significantly correlated with pAkt expression in GC
      tissues. Furthermore, pAkt expression was correlated with poor prognosis. These
      results suggest that the PI3K-Akt pathway plays an important role in HER2
      positive GC. Moreover, PIK3CA mutations and/or PTEN inactivation might affect the
      effectiveness of HER2-targeting therapy. Hence, it is necessary to clarify not
      only HER2 alterations but also PI3K-Akt pathway alterations for HER2-targeting
      therapy in GC. This review will introduce recent investigations and consider the
      current status of HER2-targeted therapy for treatment of GC.

PMID- 24458108
TI  - Biomarkers for predicting the efficacy of anti-epidermal growth factor receptor
      antibody in the treatment of colorectal cancer.
AB  - Anti-epidermal growth factor receptor (EGFR) antibodies have been widely utilized
      as a standard treatment for metastatic colorectal cancer (CRC). Anti-EGFR
      antibodies bind competitively to EGFRs to inhibit receptor activation and
      subsequent signal transduction of the RAS/RAF/MEK pathway and PI3K/AKT pathway.
      By inhibiting EGFR-mediated signal transduction, anti-EGFR antibodies inhibit
      cell growth, invasion, metastasis and angiogenesis, and they induce apoptosis.
      The IgG1-type antibody cetuximab is also capable of inducing antibody-dependent
      cellular cytotoxicity. Several studies have shown that KRAS mutation is a useful
      biomarker for predicting the efficacy of anti-EGFR agents, and the major
      guidelines for the treatment of CRC recommend the use of anti-EGFR antibody only
      for the cancers with wild-type KRAS. Alterations of other genes, including BRAF,
      NRAS, PTEN and AKT, and EGFR expression/gene copy number have also been reported
      to be candidate biomarkers for predicting the efficacy of anti-EGFR agents. The
      predictive values of these biomarkers are still controversial and further
      investigations are required.

PMID- 24458109
TI  - Advancing magnetic resonance imaging in Crohn's disease.
AB  - Crohn's disease (CD) is a lifelong chronic inflammatory bowel disease associated
      with diarrhea, abdominal pain, bloody stool and often perianal fistulae.
      Inflammation in CD involves the entire gastrointestinal tract, especially
      including the small and large bowels, causing irreversible bowel damage. Frequent
      imaging examinations are necessary to monitor disease activity and to evaluate
      response to therapeutic interventions, and, furthermore, to predict recurrence in
      order to provide appropriate treatment. The suitable imaging modality should be
      reproducible, well tolerated, safe and free of ionizing radiation. In recent
      years, imaging used in CD has dramatically changed. Cross-sectional imaging
      techniques such as computed tomography and magnetic resonance imaging (MRI) are
      used to investigate not only extraluminal abnormalities, but also intraluminal
      changes. Recently, new techniques such as MR enteroclysis, enterography,
      colonography and enterocolonography have been developed. These recent advances
      enable the use of MRI to assess bowel disorders with high sensitivity,
      specificity and accuracy. MRI can evaluate simultaneously the bowel surface,
      bowel wall, abdominal abscesses and perianal lesions, such as perianal fistulae
      and perianal abscesses, without the problem of overlapping bowel loops.
      Therefore, MRI has the potential for evaluation of the overall disease activity
      of CD without radiation exposure. We believe that MRI is a suitable first choice
      imaging modality in the assessment of CD.

PMID- 24458110
TI  - Short-chain fatty acid receptor and its contribution to glucagon-like peptide-1
      release.
AB  - BACKGROUND: Gut microbiota affects host homeostasis and dysbiosis causes host
      diseases. Therefore, uncovering the sensing mechanism of bacterial metabolites
      such as short-chain fatty acid (SCFA) may help us to understand the host
      microbiota interaction both in physiological and nonphysiological conditions.
      SUMMARY: The colonic lumen is continually exposed to many kinds of chemicals,
      including beneficial and harmful compounds that are produced by gut microbiota in
      addition to ingested nutrients. In the mammalian colon SCFAs such as acetate,
      propionate and butyrate are produced by bacterial fermentation and reach about
      100 mM under physiological conditions. In this decade, SCFA receptor genes and
      their expression in the intestine have been identified as free fatty acid
      receptor (FFA)2 and FFA3. The FFAs are located in colonic enteroendocrine L cells
      producing and releasing an insulinotropic hormone, glucagon-like peptide-1 (GLP
      1), and an anorectic hormone, peptide YY. Recent in vivo and in vitro studies
      suggest that SCFAs stimulate gut hormone secretion. Therefore, the SCFA-FFA
      signal is likely to be important for gut physiological functions. KEY MESSAGE:
      Colonic epithelial cells express chemical receptors that detect the luminal
      contents, particularly bacterial metabolites, and may be involved in the host's
      energy metabolism via GLP-1 release, as well as the mucosal defense system.

PMID- 24458111
TI  - Short-term outcomes of colorectal endoscopic submucosal dissection performed by
      trainees.
AB  - BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a relatively new
      therapy that has been accepted as the most effective treatment procedure for
      superficial colorectal neoplasms. Given the increasing acceptance and use of this
      procedure worldwide, the outcomes of colorectal ESD performed by trainees should
      be understood from a practical perspective and for developing strategies to
      introduce ESD to trainees. This study aimed to evaluate the clinical outcomes of
      ESD when conducted by less-experienced endoscopists. SUMMARY: We retrospectively
      reviewed the clinical outcomes of 164 patients with 164 colorectal neoplasms who
      underwent ESD carried out by 20 trainees performing their first colorectal ESDs
      between April 2005 and March 2012. For each operator, clinical data were
      collected between the first and 30th cases. For evaluating the technical aspects
      of the ESD procedure, the endoscopic characteristics of the lesions, procedure
      time, en bloc resection rate, R0 resection rate, invasion depth and complications
      were evaluated. The median procedure time was 95 min; about 75% of the lesions
      were resected within 120 min. Apparent perforation or electric damage in the
      muscularis propria was seen in 4% of lesions. In terms of factors with the
      potential to effect procedure time, lesion size and pathological invasion depth
      were significantly different between shorter and longer treatment times for
      granular-type laterally spreading tumors (LST). KEY MESSAGES: A granular-type LST
      of <40 mm is a good lesion for introducing colorectal ESD to trainees. Trainees
      should have a strong ability to make a depth diagnosis before starting ESD.

PMID- 24458112
TI  - Predictive value of optimal morphologic response to first-line chemotherapy in
      patients with colorectal liver metastases.
AB  - BACKGROUND: It has been reported that morphologic response to preoperative
      chemotherapy is an independent prognostic factor in patients who undergo hepatic
      resection of colorectal liver metastases (CLM). The aim of this study was to
      evaluate the predictive value of morphologic response to first-line chemotherapy
      in patients with CLM. METHODS: We assessed 41 patients with CLM who received
      fluorouracil-based chemotherapy with or without bevacizumab as the first-line
      chemotherapy between April 2006 and June 2012. Three blinded radiologists
      evaluated computed tomography images and classified them as optimal, incomplete
      or no response according to the morphologic criteria. Response to systemic
      chemotherapy was also evaluated according to Response Evaluation Criteria in
      Solid Tumors (RECIST). Predictive factors associated with progression-free
      survival (PFS) were identified in multivariate analysis. RESULTS: Twenty-three
      patients (56%) received chemotherapy with bevacizumab, while 18 patients (44%)
      received chemotherapy without bevacizumab. Optimal morphologic response was
      observed in 11 patients (48%) treated with bevacizumab and in 5 patients (28%)
      treated without bevacizumab (p = 0.19). Eight patients (20%) underwent hepatic
      resection after chemotherapy. The median follow-up period was 31.3 months. The
      median PFS was 13.3 months for patients with optical morphologic response and 8.7
      months in those with incomplete/no morphologic response (p = 0.0026). On
      multivariate analysis, performance status and morphologic response were
      significant independent predictors of PFS. CONCLUSION: Optimal morphologic
      response was significantly associated with PFS in patients with CLM who were
      treated with fluorouracil-based chemotherapy as the first-line chemotherapy.

PMID- 24458113
TI  - Prediction of maintained mucosal healing in patients with Crohn's disease under
      treatment with infliximab using diffusion-weighted magnetic resonance imaging.
AB  - BACKGROUND: Maintenance of mucosal healing may lead to a better outcome in
      patients with Crohn's disease (CD). Magnetic resonance diffusion-weighted imaging
      (MR-DWI) scans 1 year after infliximab (IFX) induction therapy were assessed as
      predictors of maintained response, or remission, through 3 years of treatment in
      patients with CD. SUMMARY: MR-DWI and endoscopy data were prospectively collected
      throughout IFX treatment. Altogether, 86 lesions from 13 patients given IFX as
      induction (weeks 0, 2 and 6) and maintenance (5 mg/kg every 8 weeks beginning at
      week 14) therapy were analyzed with MR-DWI for 0.5-1.5 years from the starting
      point. Mucosal findings were confirmed by endoscopy at 1 and 3 years (gold
      standard). Of the 86 lesions, 65 were graded '0' and 21 were graded '1' based on
      their hyperintensity (HI; or lack thereof) on MR-DWI. Two years after the first
      evaluation, 7 of 15 false-negative lesions had turned positive based on
      colonoscopy findings, and 60 of 62 true-negative lesions had not. Thus, 0.03% of
      those predicted to remain in remission had relapsed (negative predictive value
      0.9677, p < 0.0001). MR-DWI-HI at 1 year coincided with the presence of
      endoscopic inflammation, with sensitivity of 66.67%, specificity of 80.52%, and
      an area under the curve (AUC) value of 0.7359 (0.5479-0.9240, p = 0.0211). The
      AUC value of MR-DWI-HI at 3 years was 0.8402 (0.7460-0.9343, p = 0.001) with
      sensitivity of 94.12% and specificity of 73.91%. KEY MESSAGE: A definition of the
      response on the basis of MR-DWI-HI might be helpful for optimizing treatment for
      patients with CD under treatment with IFX.

PMID- 24458114
TI  - Efficacy of salvage therapy and its effect on operative outcomes in patients with
      ulcerative colitis.
AB  - AIMS: To evaluate the efficacy and safety of salvage therapy, and to identify
      risk factors of operative complications among hospitalized ulcerative colitis
      (UC) patients. PATIENTS AND METHODS: We evaluated 88 UC patients hospitalized at
      our center between April 2010 and November 2012. We compared characteristics of
      corticosteroid-refractory patients treated with calcineurin inhibitor and those
      with infliximab as second-line therapy. Furthermore, we compared the
      characteristics of operative and nonoperative patients. The association between
      perioperative treatments and complications was also investigated. RESULTS:
      Calcineurin inhibitor and infliximab were used in 42 and 22 patients,
      respectively. We found no difference in the clinical background between them.
      Efficacy rates were 67 and 50%, respectively. Eight out of 10 nonresponders of
      each treatment were treated with the other drug as third-line therapy. The
      efficacy rates of calcineurin inhibitor and infliximab as the third-line therapy
      were 75 and 50%, respectively. Operative patients had more severe disease (87.5
      vs. 31%, p < 0.01), higher Lichtiger score (14.1 vs. 11.5, p < 0.01), higher
      Rachmilewitz endoscopic index (10.5 vs. 8.4, p < 0.01), higher C-reactive protein
      (7.6 vs. 4.0, p = 0.015) and lower serum albumin (3.1 vs. 3.6, p = 0.014) than
      nonoperative patients. Complications were observed in 7 out of 16 (44 %)
      operative patients. Postoperative complications were not increased even when
      patients were treated with second- or third-line therapy. However, the
      complication rate in corticosteroid users was 54.5 (6/11) and 20% (1/5) in
      nonusers. CONCLUSIONS: Third-line salvage therapy is effective and tolerable in
      carefully selected UC patients. Perioperative use of corticosteroids may lead to
      more adverse outcomes.

PMID- 24458115
TI  - The role of gastroesophageal reflux in relation to symptom onset in patients with
      proton pump inhibitor-refractory nonerosive reflux disease accompanied by an
      underlying esophageal motor disorder.
AB  - BACKGROUND: The symptom improvement rate is low with proton pump inhibitors
      (PPIs) in nonerosive reflux disease (NERD). The underlying pathogenic mechanism
      is complex. Esophageal motility disorders (EMDs) are thought to be a factor, but
      their prevalence, type, symptoms and the role played by gastroesophageal reflux
      (GER) in symptom onset have not been fully investigated. AIM: To investigate the
      role of GER in symptom onset in PPI-refractory NERD patients with EMDs. METHODS:
      This study comprised 76 patients with PPI-refractory NERD. Manometry was
      performed during PPI treatment and patients were divided into an EMD group and
      normal motility (non-EMD) group. Then, multichannel intraluminal impedance-pH
      monitoring was performed and medical interviews were conducted. RESULTS: Nineteen
      patients (25%) had an EMD. Data were compared between 17 patients, excluding 2
      with achalasia and 57 non-EMD patients. No significant differences were observed
      between groups in 24-hour intraesophageal pH <4 holding time (HT), mean number of
      GER episodes or mean number of proximal reflux episodes. The reflux-related
      symptom index (>=50%) showed a relationship between reflux and symptoms in 70.5%
      of EMD patients and 75% of non-EMD patients. In the EMD group, the score for FSSG
      (Frequency Scale for the Symptoms of GERD) question (Q)10 was significantly
      correlated with the number of GER episodes (r = 0.58, p = 0.02) and the number of
      proximal reflux episodes (r = 0.63, p = 0.02). In addition, the score for Q9
      tended to be correlated with the number of GER episodes (r = 0.44, p = 0.06).
      CONCLUSION: Our results suggest that some PPI-refractory NERD patients have EMDs,
      and that GER plays a role in symptom onset.

PMID- 24458118
TI  - The origin of unusual chromosome constitutions among newly formed allopolyploids.
AB  - PREMISE OF THE STUDY: Wide hybridization followed by spontaneous chromosome
      doubling of the resulting hybrids plays an important role in plant speciation.
      Such chromosome doubling is usually accomplished via unreduced gametes produced
      by altered meiosis, the so-called 'meiotic restitution'. Unreduced gametes are
      expected to carry somatic chromosome numbers and constitutions. However, it has
      been shown recently that new allopolyploids often carry unusual chromosome
      constitutions which include compensating and noncompensating nulli-tetrasomies
      and monotrisomies, and translocations of homoeologues. METHODS: We have
      reanalyzed meiotic divisions in a wheat-rye hybrid by in situ probing with
      labeled DNA focusing on deviations from the standard pattern of meiotic
      restitution. KEY RESULTS: In a typical first division restitution in a wide
      hybrid, there is no chromosome pairing, univalents separate sister chromatids in
      anaphase I, and there is no meiosis II. Here we illustrate that occasional
      pairing of homoeologous chromosomes in metaphase I, combined with separation of
      sister chromatids of univalents, generates diads with compensating nulli-disomies
      and associated translocations of homoeologues. Similarly, precocious metaphase I
      migration to the poles of some undivided univalents generates a wide range of
      noncompensating simple and complex nulli-disomies in the gametes. CONCLUSIONS:
      Both alterations to the standard pattern of meiotic restitution tend to maintain
      the somatic chromosome numbers in the gametes; chromosome constitutions are
      variable but mostly genetically balanced. This source of variation among progeny
      may be an important factor contributing to greater success of natural
      allopolyploids.

PMID- 24458117
TI  - A questionnaire-based survey on the diagnosis and management of inflammatory
      bowel disease in East Asian countries in 2012.
AB  - BACKGROUND AND AIM: The prevalence and incidence of inflammatory bowel disease
      (IBD) are lower in East Asia than in Western countries; however, marked increases
      have recently been reported. The clinical diagnosis and medical management of IBD
      in East Asia differ from those in Western countries. A questionnaire-based survey
      was performed to gather physicians' current opinions on IBD in different East
      Asian countries. METHODS: Representative International Gastrointestinal Consensus
      Symposium (IGICS) committee members provided a questionnaire to physicians in
      each East Asian country studied. The questionnaire mainly focused on the
      diagnosis and management of IBD. RESULTS: There were 19 respondents from Japan,
      10 from South Korea, 9 from the Philippines, 6 from China and 4 from Indonesia.
      Colonoscopy (100%) and histopathology (63%) were commonly used for the diagnosis
      in ulcerative colitis (UC). Conventional small bowel enteroclysis was still the
      most common diagnostic tool for assessing small bowel lesions in Crohn's disease
      (CD) in East Asia. The percentage of physicians who investigated the reactivation
      of Cytomegalovirus in severe or refractory patients with UC ranged from 0% in the
      Philippines and Indonesia to 100% in Japan and Korea. Most physicians in Korea,
      the Philippines, China and Indonesia chose thiopurines or anti-TNF therapy as the
      second-line treatment in severe refractory UC, whereas Japanese physicians
      preferred to use tacrolimus or leukocyte apheresis. Physicians in the Philippines
      and Indonesia preferred to use oral 5-aminosalicylic acid for newly diagnosed
      severe ileocecal CD. In contrast, Korean physicians chose oral steroids and most
      physicians in China and Japan preferred to use anti-TNF. Nutritional therapy to
      induce or maintain remission in patients with CD was commonly used in Indonesia,
      Japan and China. Targeted biopsies by conventional colonoscopy were the most
      preferred strategy for cancer surveillance in long-standing UC over random
      biopsies in this region. CONCLUSIONS: The present survey found that current
      diagnostic approaches and clinical management of IBD vary within East Asian
      countries.

PMID- 24458119
TI  - Ecological relationship between floral thermogenesis and pollination in Nelumbo
      lutea (Nelumbonaceae).
AB  - PREMISE OF STUDY: Floral thermogenesis is an unusual floral trait with a well
      documented physiological process, and yet, there is limited understanding of how
      this trait influences plant reproduction. The current study was undertaken to
      gain a better understanding of how floral thermogenesis in Nelumbo lutea impacts
      pollinator attraction and consequent plant reproduction. METHODS: We conducted
      field studies on floral thermogenesis and thermoregulation, flower sexual
      development, floral visitation patterns, breeding system, pollen transfer
      dynamics, and floral scent production. KEY RESULTS: The most abundant visitors to
      the thermoregulatory flowers included the Phoridae (Diptera), Chrysomelidae
      (Coleoptera), and Hymenoptera. Chrysomelid beetles, particularly Diabrotica, were
      frequent visitors to both first-day female- and second-day bisexual-phase
      flowers, while phorid flies were most common in bisexual-phase flowers. Pollen
      transfer experiments indicated that Diabrotica was equally effective in
      depositing pollen on stigmas, as were the less frequent, but pollen-loaded
      halictid bees. CONCLUSIONS: Flowers received a taxonomically wide assemblage of
      floral visitors and appear adapted to attract beetles, primarily Chrysomelidae
      and medium-sized bees. This study is the first to provide strong support that
      beetles can comprise the dominant portion of floral visitors and are as effective
      in pollen transfer as bees. Thermogenesis aids in dispersing the main floral
      scent component-1,4-dimethoxybenzene-attracting both chrysomelids and bees, while
      thermoregulation causes chrysomelid beetles to actively seek out new flowers for
      evening residence. This search behavior likely results in chrysomelids affecting
      cross-pollination.

PMID- 24458120
TI  - Changes in phytic acid and phytase during early development of Phaseolus vulgaris
      L.
AB  - Changes in phytic acid, phytase, and inorganic phosphate were examined in the
      cotyledon of Phaseolus vulgaris L cv. Taylor's Horticultural during embryogeny
      and germination. Embryogeny normally requires 36 days in this cultivar. Phytic
      acid is accumulated most rapidly between days 24 and 30. Coincident with this
      increase, relatively high values of inorganic phosphate were observed in the
      cotyledon. The inorganic phosphate in the developing cotyledon does not decrease
      until dehydration phase. This decrease cannot be entirely accounted for by the
      residual synthesis of phytic acid during this time. These data, along with data
      from the literature, suggest that close coordination exists between the
      biochemical systems responsible for the deposition of storage reserves in the
      cotyledon. Phytase activity remained undetectable during embryogeny. However, a
      rapid rise in phytase activity was observed commencing after day 2 of
      germination. The increased activity of phytase was well correlated with the
      disappearance of its substrate, phytic acid, from the cotyledon. Phosphate levels
      remained much lower than those observed during embryogeny. 

PMID- 24458121
TI  - Uptake of [2-(14)C] mevalonic acid by lipid and glycoside sterols.
AB  - D. L. [2-(14)C] mevalonic acid was fed to Digitalis purpurea flowering plants and
      the 4-4'-dimethyl and phytosterol fractions isolated at time intervals from the
      glucoside and lipid portions of the plant extract. The incorporation of mevalonic
      acid was determined in both the aerial parts and the roots over a period of 35
      days. In the aerial parts the uptake of radioactivity was rapid in the
      cycloartenol and lipid phytosterol fractions, but less so in the glucoside
      phytosterols. In the roots the glucoside phytosterols incorporation of label was
      considerably more rapid than in the lipid fraction. 

PMID- 24458122
TI  - Chlorophyll accumulation by callus tissues of Glycine max.
AB  - On illumination, soybean (Glycine max) callus tissue culture accumulated
      chlorophyll and this was most rapidly formed at the time of maximum growth. These
      results are discussed in terms of the relationship between growth and greening of
      tissue cultures. 

PMID- 24458123
TI  - Basipetal and acropetal transport of [3,4-(3)H]Gibberellin A 1 in short and long
      segments of Phaseolus coccineus second internode.
AB  - Transport of [(3)H]GA1 occurred freely through stem segments ranging in length
      from 6 mm to 8 cm. Only small amounts of radioactivity appeared in agar receiver
      blocks, particularly when transport in young, elongating, segments was measured.
      Little or no metabolism of [(3)H]GA1 appeared to take place during a 16 h
      transport period. With 6 mm segments, there was no indication of polarity in
      longitudinal transport. In 8 cm long segments, an apparent acropetal polarity of
      [(3)H]GA1 transport occurred in young, but not in mature, segments. However, it
      appeared likely that gibberellin transport, even in long young segments, was not
      truly polar, but could be influenced by the spatial distribution of growth
      centres in relation to gibberellin source. 

PMID- 24458124
TI  - [Relations between carbonic anhydrase activity and uptake of HCO3 (-) and Cl (-)
      in photosynthesis by Scenedesmus obliquus].
AB  - Synchronized, young cells of Scenedesmus obliquus when adapted to air plus 1.5%
      CO2 have only about 1/20 of the carbonic anhydrase activity of air-adapted cells.
      At pH 9.2 (where HCO3 (-) is the prevailing form of inorganic carbon) such
      cultures do not evolve much O2 at 50.10(3) lux, in contrast to air-adapted cells.
      In contrast, at pH 5.8 (where CO2 prevails) there is not much difference in O2
      evolution rate between cultures adapted to different CO2-levels. It is concluded
      that carbonic anhydrase activity is necessary for the utilisation of HCO3 (-) but
      not of CO2 in photosynthesis by Scenedesmus.Air-adapted cells take up about 0.3
      MUmoles Cl(-)/g FW from 0.1 mM KCl solution (pH 5.8) within the first minute of
      illumination. The same amount is released when the light is switched off. The
      light induced Cl(-)-uptake is inhibited by addition of HCO3 (-) or high pH, and
      may be interpreted as an alternative uptake of Cl(-) instead of HCO3 (-).As cells
      adapted to air plus 1.5% CO2 do not show this light induced Cl(-)-uptake and as
      the inhibitor of carbonic anhydrase, diamox, affects Cl(-)-uptake of air-adapted
      cells, it is suggested that carbonic anhydrase may be involved in the uptake of
      Cl(-) and HCO3 (-). 

PMID- 24458125
TI  - Stimulation of polyphenol oxidase (monophenolase) activity in wheat endosperm by
      gibberellic acid, cycloheximide and actinomycin D.
AB  - Embryoless wheat (Triticum aestivum L.) half-seeds on incubation with gibberellic
      acid (GA3) showed a 2- to 2.5fold stimulation of monophenolase activity. The
      enzyme activity was not released into the incubation medium in GA3-treated half
      seeds. The effect of GA3 was counteracted by the addition of abscisic acid (ABA)
      to the half-seeds. Adenosine-3',5'-cyclic monophosphate and its structural
      analogues were ineffective in increasing the monophenolase activity. Actinomycin
      D and cycloheximide showed no inhibitory effecton the monophenolase activity in
      controls as well as in GA3-treated half-seeds, but on the contrary caused a 2- to
      3fold stimulation of enzyme activity similar to that observed in endosperm
      treated with GA3 alone. However, there was no additive or synergistic enhancement
      of monophenolase activity when GA3 was tested in combination with cycloheximide
      or actinomycin D. GA3- or cyclic AMP-treated half-seeds showed no stimulation of
      o-diphenolase activity. 

PMID- 24458126
TI  - [The nitrate- and nitrite-dependent O2-evolution in N 2 by Ankistrodesmus
      braunii].
AB  - O2-evolution in N2 by young cells of synchronous Ankistrodesmus braunii was
      measured manometrically in the presence and in the absence of nitrate or nitrite.
      Nitrate-starved cells produce O2 as a function of nitrate concentration with an
      optimum at 10 mM nitrate. The optimum rates are strongly dependent upon the pH of
      the medium culminating at pH 8.0.Nitrite excretion is initially slow and has its
      optimum at the same nitrate concentration as O2-evolution. It is slower under
      anaerobic conditions than in the presence of CO2 and slower at pH 5.6 than at pH
      8.0. At pH 8.0 in N2 an accumulation of nitrite starts 40 to 100 min after the
      addition of nitrate to the algae.O2-evolution is faster with nitrite than with
      nitrate. No optimum curve is observed at pH 8.0 with various concentrations of
      nitrite in the medium; however, at pH 5.6 a distinct peak is found at 3 mM
      nitrite. This peak is found for a fast short-time reaction as well as for the
      following low rates of O2-evolution.The uncoupler carbonylcyanide-m
      chlorophenylhydrazone (CCCP) equally inhibits nitrate- and nitrite-dependent O2
      evolution and the incorporation of (32)P into cellular phosphate compounds. There
      is no indication of uncoupling in vivo of nitrite reduction which is completely
      independent of ATP in vitro. The inhibition of the nitrate-dependent O2-evolution
      by high concentrations of nitrate cannot be explained by an accumulation of
      products such as ammonia or nitrite. 

PMID- 24458127
TI  - [The action of statoliths in the geotropic response of the roots of lens
      culinaris L].
AB  - The possibility of a relationship between the geotropic response and the
      sedimentation of amyloplasts was studied.In the first experiment the geotropic
      curvature and the statolithic apparatus of the roots were defined individually.
      Statistical analysis showed no correlation between curvature (in its initial
      phase) and the average number of amyloplasts per cell in section, their average
      volume and the space that they occupy in the statocyte. These findings seem to
      exclude the possibility of the statoliths acting by pressure on some sensitive
      surface.In the second experiment the initial rate of curvature and the percentage
      of amyloplasts along the longitudinal wall were analysed as a function of the
      angle of inclination relative to direction of gravity (45-150 degrees ). The
      results obtained show that at the various angles the initial rate of curvature is
      not dependent on the percentage of amyloplasts which are in contact with a
      sensitive surface. Nor can the displacement of the amyloplasts caused by the
      change of orientation explain the relationship between the degree of curvature
      and the angle of inclination. It seems that no direct link can be found between
      the sedimentation of the amyloplasts and the geotropic reaction in its initial
      phase. These results are discussed in reference to recent literature on the
      existence of growth inhibitors that could be responsible for the geotropic
      response. 

PMID- 24458128
TI  - The effect of abscisic acid on the uptake of potassium and chloride into Avena
      coleoptile sections.
AB  - The effect of abscisic acid (ABA) on uptake of potassium ((86)Bb(+) or (42)K(+))
      by Avena sativa L. coleoptile sections was investigated. ABA lowered the
      potassium uptake rate within 30 min after its application and inhibition reached
      a maximum (ca. 75%) after 2 h. The inhibition of K(+) uptake increased with ABA
      concentration over a range of 0.03 to 10 MUg/ml ABA. At a higher K(+)
      concentration (20 mM) the percentage inhibition decreased. The percentage
      inhibition of K(+) uptake by ABA remained constant with external K(+) varied from
      0.04 to 1.0 mM. After a loading period in 20 mM K(+) ((86)Rb(+)), apparent efflux
      of potassium was only slightly increased by ABA. Experiments in which growth was
      greatly reduced by mannitol or by omission of indole-3-acetic acid from the
      medium indicated there was no simple quantitative correspondence between ABA
      inhibition of coleoptile elongation and ABA inhibition of K(+) uptake. Chloride
      uptake was also inhibited by ABA but to a smaller degree than was K(+) uptake. No
      specificity for counterions was observed for K(+) uptake. Uptake of 3,0
      methylglucose and proline were inhibited by ABA to a much smaller extent (14 and
      11%) than that of K(+), a result which suggests that ABA acts on specific ion
      uptake mechanisms. 

PMID- 24458130
TI  - Callyspongisines A-D: bromopyrrole alkaloids from an Australian marine sponge,
      Callyspongia sp.
AB  - An extract of the Great Australian Bight marine sponge Callyspongia sp. (CMB
      01152) displayed inhibitory activity against the neurodegenerative disease kinase
      targets casein kinase 1 (CK1), cyclin-dependent kinase 5 (CDK5) and glycogen
      synthase kinase 3 (GSK3beta). Chemical investigation, employing HPLC-DAD-MS
      single ion extraction protocols, facilitated identification of the new
      bromopyrrole alkaloids, callyspongisines A-D (1-4), and two known co-metabolites,
      hymenialdisine (5) and 2-bromoaldisine (6). Structure elucidation of 1-6 was
      supported by detailed spectroscopic analysis and chemical interconversion, as
      well as biosynthetic and synthetic considerations. Callyspongisine A (1) is only
      the second reported example of a natural imino-oxazoline, and the first to
      feature a spiro heterocyclic framework, while callyspongisines B-D (2-4) were
      speculated to be storage and handling artefacts of 1. The kinase inhibitory
      activity detected in Callyspongia sp. (CMB-01152) was attributed to 5.

PMID- 24458129
TI  - Hsa-miR-520d induces hepatoma cells to form normal liver tissues via a stemness
      mediated process.
AB  - The human ncRNA gene RGM249 regulates the extent of differentiation of cancer
      cells and the conversion of 293FT cells to hiPSCs. To identify the factors
      underlying this process, we investigated the effects of lentivirally inducing miR
      520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor
      formation in a xenograft model. Transformed HLF cells were Oct4 and Nanog
      positive within 24 h, showed p53 upregulation and hTERT downregulation, and
      mostly lost their migration abilities. After lentiviral infection, the cells were
      intraperitoneally injected into mice, resulting in benign teratomas (6%), the
      absence of tumors (87%) or differentiation into benign liver tissues (7%) at the
      injection site after 1 month. We are the first to demonstrate the loss of
      malignant properties in cancer cells in vivo through the expression of a single
      microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to
      hiPSC-like cells. The regulation of malignancy by miR-520d appears to be through
      the conversion of cancer cells to normal stem cells, maintaining p53
      upregulation.

PMID- 24458131
TI  - Association of prostate size and perioperative morbidity in thulium:YAG
      vapoenucleation of the prostate.
AB  - OBJECTIVE: To evaluate the association between perioperative morbidity and
      prostate size in patients with benign prostatic obstruction treated with
      thulium:YAG vapoenucleation of the prostate (ThuVEP). METHODS: 687 patients were
      prospectively analyzed. Prostate size was <40 ml in 196 (group A), 40-79 ml in
      336 (group B) and >=80 ml in 155 (group C) patients. RESULTS: The mean prostate
      sizes were 27.94 +/- 6.77, 54.38 +/- 10.54 and 109.8 +/- 28.31 ml for groups A, B
      and C, respectively (p < 0.001). Hemoglobin loss (g/dl) differed significantly
      among group A (1.09 +/- 1.02), group B (1.28 +/- 1.27) and group C (1.62 +/-
      1.49) (p < 0.001). The correlation between hemoglobin loss and prostate size was
      very weak in all patients (r = 0.13, p <= 0.001). Peak urinary flow rates and
      post-voiding residual urine improved significantly (p < 0.001) without
      differences among the groups. The incidence of complications was low and not
      different among the groups (acute urinary retention 8%, urinary tract infection
      4.66%, secondary apical resection 2.91%, transfusion rate 2.03%). CONCLUSIONS:
      Perioperative morbidity and micturition improvement are not associated with
      prostate size in ThuVEP.

PMID- 24458132
TI  - Processing of laminin alpha chains generates peptides involved in wound healing
      and host defense.
AB  - Laminins play a fundamental role in basement membrane architecture and function
      in human skin. The C-terminal laminin G domain-like (LG) modules of laminin alpha
      chains are modified by proteolysis to generate LG1-3 and secreted LG4-5 tandem
      modules. In this study, we provide evidence that skin-derived cells process and
      secrete biologically active peptides from the LG4-5 module of the laminin alpha3,
      alpha4 and alpha5 chain in vitro and in vivo. We show enhanced expression and
      processing of the LG4-5 module of laminin alpha3 in keratinocytes after infection
      and in chronic wounds in which the level of expression and further processing of
      the LG4-5 module correlated with the speed of wound healing. Furthermore,
      bacterial or host-derived proteases promote processing of laminin alpha3 LG4-5.
      On a functional level, we show that LG4-5-derived peptides play a role in wound
      healing. Moreover, we demonstrate that LG4-derived peptides from the alpha3,
      alpha4 and alpha5 chains have broad antimicrobial activity and possess strong
      chemotactic activity to mononuclear cells. Thus, the data strongly suggest a
      novel multifunctional role for laminin LG4-5-derived peptides in human skin and
      its involvement in physiological processes and pathological conditions such as
      inflammation, chronic wounds and skin infection.

PMID- 24458133
TI  - Cilostazol inhibits insulin-stimulated expression of sterol regulatory binding
      protein-1c via inhibition of LXR and Sp1.
AB  - Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an
      important hepatic manifestation of metabolic syndrome. Sterol regulatory binding
      protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the
      liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver
      X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet
      agent that prevents atherosclerosis and decreases serum triglyceride levels.
      However, little is known about the effects of cilostazol on hepatic lipogenesis.
      Here, we examined the role of cilostazol in the regulation of SREBP-1c
      transcription in the liver. The effects of cilostazol on the expression of SREBP
      1c and its target genes in response to insulin or an LXR agonist (T0901317) were
      examined using real-time RT-PCR and western blot analysis on cultured
      hepatocytes. To investigate the effect of cilostazol on SREBP-1c at the
      transcriptional level, transient transfection reporter assays and electrophoretic
      mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin
      induced and LXR-agonist-induced expression of SREBP-1c and its downstream
      targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes.
      Cilostazol also inhibited activation of the SREBP-1c promoter by insulin,
      T0901317 and Sp1 in a luciferase reporter assay. EMSA analysis showed that
      cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1
      to the promoter region. These results indicate that cilostazol inhibits insulin
      induced hepatic SREBP-1c expression via the inhibition of LXR and Sp1 activity
      and that cilostazol is a negative regulator of hepatic lipogenesis. 

PMID- 24458134
TI  - Factors associated with heat strain among workers at an aluminum smelter in
      Texas.
AB  - OBJECTIVES: To determine the prevalence of heat strain and factors associated
      with heat strain among workers at an aluminum smelter in Texas. METHODS:
      Continuous core body temperature (T(c)), heart rate, and pre- and postshift serum
      electrolytes, and urine specific gravity were measured, and symptom
      questionnaires were administered. RESULTS: Most participants (54%) had 1 or more
      signs of heat strain. Unacclimatized participants were significantly more likely
      to exceed the American Conference of Governmental Industrial Hygienists
      recommended T(c) than acclimatized participants (88% vs 20%; P < 0.01).
      Participants who exceeded the T(c) for their acclimatization status and/or
      exceeded the recommended sustained peak HR had a significantly lower body mass
      index than those who did not (27.6 vs 31.8 and 28.4 vs 32.4, respectively; P =
      0.01). CONCLUSIONS: Employees and management need to strictly adhere to a heat
      stress management program to minimize heat stress and strain.

PMID- 24458136
TI  - [Prof. Dr. Karl-Horst Bichler on the occasion of his 80th birthday].

PMID- 24458135
TI  - Use of pHluorin to assess the dynamics of axon guidance receptors in cell culture
      and in the chick embryo.
AB  - During development, axon guidance receptors play a crucial role in regulating
      axons sensitivity to both attractive and repulsive cues. Indeed, activation of
      the guidance receptors is the first step of the signaling mechanisms allowing
      axon tips, the growth cones, to respond to the ligands. As such, the modulation
      of their availability at the cell surface is one of the mechanisms that
      participate in setting the growth cone sensitivity. We describe here a method to
      precisely visualize the spatio-temporal cell surface dynamics of an axon guidance
      receptor both in vitro and in vivo in the developing chick spinal cord. We took
      advantage of the pH-dependent fluorescence property of a green fluorescent
      protein (GFP) variant to specifically detect the fraction of the axon guidance
      receptor that is addressed to the plasma membrane. We first describe the in vitro
      validation of such pH-dependent constructs and we further detail their use in
      vivo, in the chick spinal chord, to assess the spatio-temporal dynamics of the
      axon guidance receptor of interest. 

PMID- 24458139
TI  - A contact-corrected density functional theory for electrolytes at an interface.
AB  - We present a contact-corrected density functional theory for ionic distributions
      at an interface that not only accounts for the steric effects and electrostatic
      correlations often ignored by conventional electrochemical methods but also
      conforms to the exact statistical-mechanical sum rule for the contact ionic
      densities. The theoretical predictions are in excellent agreement with the
      simulation results for both the interfacial structure and electrochemical
      properties over a wide variety of electric double layer systems including those
      containing asymmetric electrolytes with multivalent ions. 

PMID- 24458137
TI  - Hepatic safety and tolerability of raltegravir among HIV patients coinfected with
      hepatitis B and/or C.
AB  - BACKGROUND: Potential liver toxicity is an important consideration for
      antiretroviral selection among patients coinfected with HIV and viral hepatitis
      (B and/or C). We sought to describe the hepatic safety profile of raltegravir in
      this population. METHODS: Using data from HIV clinical cohorts at Johns Hopkins
      University and the University of North Carolina at Chapel Hill, we evaluated
      factors associated with liver enzyme elevations (LEEs) and calculated adverse
      event incidence rates for patients initiated on raltegravir-containing regimens
      prior to 1 January 2010. LEEs were graded according to Division of AIDS
      definitions. RESULTS: During the study period, 456 patients received raltegravir 
      of whom 36% were hepatitis-coinfected (138 HCV, 17 HBV, 11 HBV+HCV). Coinfected
      patients were more likely to have baseline abnormal LEEs and developed severe
      (grade 3-4) LEEs at a rate 3.4* that of HIV-monoinfected patients (95% CI 1.28,
      9.61). Among all participants, the incidence rate for first occurrence of severe
      LEEs was 5 per 100 person-years (95% CI 3, 7). In adjusted analyses, coinfected
      patients had a 2.7-fold increased hazard of severe LEEs (95% CI 1.03, 7.04). 60%
      of severe abnormalities occurred within 6 months after starting raltegravir; the
      drug was discontinued in 3 (1.3%) coinfected patients and 18 (6.2%) monoinfected
      patients. CONCLUSIONS: Compared with HIV-monoinfected patients, those with HIV
      hepatitis coinfection are at increased hazard of developing LEEs on raltegravir,
      at a level similar to other antiretrovirals. Severe events were uncommon, rarely
      leading to raltegravir discontinuation. With appropriate monitoring, raltegravir
      based therapy is safe in hepatitis-coinfected patients.

PMID- 24458138
TI  - High prevalence of severe circulatory complications with diazoxide in premature
      infants.
AB  - BACKGROUND: Since diazoxide was approved for clinical use in Japan in 2008, its
      prescription for the treatment of infants with hyperinsulinemic hypoglycemia
      (HIH) has rapidly expanded. Concomitantly, reports of complications associated
      with diazoxide are increasing. OBJECTIVES: To clarify the trends and problems
      associated with the treatment of infants with HIH, we planned a nationwide
      surveillance in Japan. METHODS: Questionnaires were sent to 255 institutions
      belonging to the Japanese Neonatologist Association inquiring about neonatal
      cases of HIH from 2009 to 2011. RESULTS: One hundred nineteen cases of neonates
      with transient HIH (THIH) related to perinatal problems and 15 cases with
      permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were
      reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and
      the administration was completed within 3 months in 46 infants (71.9%). Fourteen
      of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had
      hypoglycemia persisting beyond a year. Circulatory complications were reported in
      15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis
      revealed that a younger gestational age at birth and higher maximum doses of
      diazoxide were significant risk factors for circulatory complications.
      CONCLUSIONS: Diazoxide is widely prescribed for infants with HIH as a first-line
      medicine in Japan, but prophylactic diuretics are uncommon. Under these
      circumstances, a high prevalence of severe circulatory complications in very-low
      birth-weight infants was reported.

PMID- 24458140
TI  - The tripod graft: nasal tip cartilage reconstruction during revision rhinoplasty.
AB  - IMPORTANCE Nasal tip revision remains one of the most challenging surgical
      procedures for facial plastic surgeons to perform. OBJECTIVE To describe
      preoperative and postoperative findings related to nasal tip functional and
      aesthetic aspects following revision rhinoplasty using the "tripod" technique.
      DESIGN, SETTING, AND PARTICIPANTS A retrospective descriptive study was performed
      in patients who underwent revision rhinoplasty between 2007 and 2012 at a clinic
      in Bogota, Colombia. A preoperative diagnosis of nasal tip deformity was made on
      the basis of photographic records and compared with postoperative nasal tip
      findings in patients who required the tripod technique. Photographs were
      evaluated before and after surgery every month for the first 3 months, and after
      6, 9, and 12 months postoperatively. MAIN OUTCOMES AND MEASURES Nasal projection,
      tip rotation, columellar and alar retraction, alar pinch, lack of tip definition,
      and nasal tip asymmetry. RESULTS Sixty-four of the 69 patients who received
      revision rhinoplasty using the tripod technique during the study period were
      enrolled in the study. The tripod technique improved all of the following
      aesthetic and functional parameters (all P < .001). Nasal tip definition improved
      in 43 of 49 patients (88%). After surgery, projection was normal in 28 of 40
      patients (70%) who had underprojection and overprojection preoperatively, and
      rotation improved in 29 of 38 patients (76%) who had overrotation or
      underrotation preoperatively. Columellar retraction improved after surgery in 18
      of 24 patients (75%). The alar region improved in 41 of 52 patients (79%) who had
      alar retraction and/or pinch preoperatively, and inspiratory collapse improved in
      49 of 50 patients (98%). CONCLUSIONS AND RELEVANCE The tripod technique is an
      efficient surgical alternative for nasal tip reconstruction during revision
      rhinoplasty. This technique allows the destroyed cartilaginous framework to be
      recreated and returns original nasal tip appearance with stable results. LEVEL OF
      EVIDENCE 4. 

PMID- 24458142
TI  - Hyperleptinemia is associated with CRP, but not apolipoprotein E, and is reduced
      by exercise training.
AB  - The purpose of this study was to examine whether leptin levels affect the
      response of leptin to exercise training (ET) and whether this is also affected by
      C-reactive protein (CRP) or the three common Apolipoprotein E genotypes (APOE).
      Ninety-seven (male = 45, female = 52) sedentary individuals underwent 6 months of
      supervised ET. Blood was sampled before the initiation of ET, and again 24 and 72
      hr after completion of the final training session. ET resulted in a small
      reduction in body mass (80.47 +/- 18.03 vs 79.42 +/- 17.34 kg, p < .01). Leptin
      was reduced 24 hr after the final exercise session (p < .01), but returned to
      normal after 72 hr (p > .05)--Pre: 13.51 +/- 12.27, 24hr: 12.14 +/- 12.34, 72 hr:
      12.98 +/- 11.40 ng/ml. The most hyperleptinemic individuals had a greater initial
      response, which was sustained through to 72 hr after the final session in the
      pooled study population (p < .01), and in both males (p < .05) and females (p <
      .05) separately. CRP was related to leptin independently of body weight and
      positively related to the reductions in leptin. APOE genotype was not related to
      leptin levels and did not affect the response to ET. Leptin levels may only be
      reduced by ET in those with hyperleptinemia. In addition, both the initial extent
      of hyperleptinemia and the subsequent reduction in leptin may be related to low
      grade chronic systemic inflammation.

PMID- 24458141
TI  - An exploratory study to subtype obese binge eaters by personality traits.
AB  - BACKGROUND: Obesity and binge eating disorder (BED) are prevalent conditions that
      severely affect the quality of life of many people in developed countries, but an
      effective treatment remains elusive. Personality traits have been studied
      extensively in this population, leading to different, and at times conflicting,
      results. Subtyping BED people along these features could add to our knowledge of
      the disorder. METHODS: We applied a two-step cluster analysis, followed by
      bootstrapping validation, to the Temperament and Character Inventory scores of
      462 subjects affected by obesity and BED or subthreshold BED. RESULTS: We found
      two clusters of subjects; however, the categorization in clusters 1 and 2 did not
      appear to strictly overlap with the distinction between BED and subthreshold BED.
      The first cluster showed higher harm avoidance and a lower self-directedness.
      Cluster 1 patients had higher depression, higher eating impulsivity, greater
      problems with their body image and poorer quality of life than cluster 2
      patients. CONCLUSIONS: Our results seem to confirm the heterogeneity of the binge
      eater population and suggest the importance of harm avoidance and self
      directedness to subtype these subjects. These results could generate exploratory
      works regarding personality in obese people with BED to discover more targeted
      treatments.

PMID- 24458143
TI  - Iridium-catalyzed selective alpha-methylation of ketones with methanol.
AB  - Iridium-catalyzed selective alpha-dimethylation and alpha-methylation of ketones
      or phenylacetonitriles, using methanol as the methylating agent, were achieved.
      In addition, three-component cross alpha-methyl-alkylation was successfully
      performed using methyl ketones with methanol and primary alcohols with long-chain
      alkyl groups. This method provides a very convenient direct route to alpha
      methylated ketones, using methanol. 

PMID- 24458144
TI  - Increased severity of inflammation correlates with elevated expression of TRPV1
      nerve fibers and nerve growth factor on interstitial cystitis/bladder pain
      syndrome.
AB  - OBJECTIVES: Although evidence supports a role for inflammation in interstitial
      cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We
      determined whether inflammation causes an elevated expression of nerve growth
      factor (NGF) and transient receptor potential vanilloid receptor subtype 1
      (TRPV1) and correlated them with the symptoms. METHODS: Bladder biopsies were
      obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin
      staining, immunostaining and Western blotting were performed to detect
      inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and
      NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency
      (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve
      fiber density was quantified and correlated with PUF scores. RESULTS: Increased
      severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve
      fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p =
      0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly
      correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r =
      0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were
      significantly increased in IC/BPS (p = 0.0193) and had a positive relationship
      with inflammation severity (r = 0.6138, p < 0.0001). CONCLUSIONS: Our study
      revealed increased severity of inflammation correlated with a higher expression
      of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with
      clinical symptoms.

PMID- 24458145
TI  - Hypoxia-reoxygenation affects whole-genome expression in the newborn eye.
AB  - PURPOSE: Resuscitation of newborns is one of the most frequent procedures in
      neonatal medicine. The use of supplementary oxygen during resuscitation of the
      asphyxiated newborn has been shown to be detrimental to vulnerable tissues. We
      wanted to assess transcriptional changes in ocular tissue after the acute use of
      oxygen in the delivery room in a hypoxia-reoxygenation model of the newborn
      mouse. METHODS: C57BL/6 mice (n = 57), postnatal day 7, were randomized to
      receive either 120 minutes of hypoxia, at 8% O2, followed by 30 minutes of
      reoxygenation with 21, 40, 60, or 100% O2 or to normoxia followed by 30 minutes
      of 21% or 100% O2. Whole ocular homogenates were analyzed by Affymetrix 750k
      expression array, and RT-PCR was performed for validation. Bayesian analysis of
      variance for microarray data (BAMarray) was used to identify single significant
      genes, and Gene Set Enrichment Analysis (GSEA) was applied to reveal significant
      pathway systems. RESULTS: In total, ~ 92% of the gene expression changes were
      altered in response to reoxygenation with 60% or 100% O2 compared to expression
      at the lower percentages of 21% and 40%. After 100% O2 treatment, genes involved
      in inflammation (Ccl12), angiogenesis (Igfr1, Stat3), and metabolism (Hk2) were
      upregulated. Pathway analyses after hypoxia-reoxygenation revealed significant
      alterations of six pathways which included apoptosis, TGF-beta signaling,
      oxidative phosphorylation, voltage-gated calcium channel complex, mitochondrion,
      and regulation of RAS protein signal transduction. CONCLUSIONS: Hypoxia
      reoxygenation can induce immediate transcriptional responses in ocular tissue
      involving inflammation, angiogenesis, energy failure, and Ras signaling.

PMID- 24458146
TI  - RTP801 gene expression is differentially upregulated in retinopathy and is
      silenced by PF-04523655, a 19-Mer siRNA directed against RTP801.
AB  - PURPOSE: The intraocular pharmacodynamics of PF-04523655, a small-interfering RNA
      (siRNA) directed against RTP801, was characterized using rat models of
      retinopathy. METHODS: Rat models of streptozotocin-induced diabetes and wet AMD
      were used to determine the onset, extent, and duration of siRNA inhibition of
      retinal RTP801 expression by PF-04523655, and this inhibition was characterized
      by pharmacokinetic/pharmacodynamic (PK/PD) modeling. A rat model of wet AMD was
      also used to examine PF-04523655 dose-dependent effects on the incidence of
      clinical grade 3 or 4 choroidal neovascularization lesions. Whole homogenate
      versus laser-capture microdissected (LCM) retinal samples were analyzed by
      quantitative PCR for RTP801 expression. RESULTS: RTP801 expression in RPE/choroid
      (RPE/C) increased in diabetic rats by up to 70% above nondiabetic rat levels.
      Inhibition of retinal RTP801 expression by PF-04523655 began 1 day after
      intravitreous injection and was observed through day 7 in the neurosensory retina
      and through day 14 or longer in RPE/C. PF-04523655 inhibition of RTP801
      expression was maintained well after clearance of PF-04523655 from the eye and
      was best characterized by an effect compartment PK/PD model. Moreover, PF
      04523655 administration decreased the incidence of clinical grade 3 or 4 lesions
      by approximately 60% (P = 0.053), and dose-dependently inhibited retinal RTP801
      expression (P < 0.01). RTP801 expression was enriched in the outer nuclear layer
      in LCM samples. CONCLUSIONS: In rodent retinopathy models, administration of the
      siRNA, PF-04523655, reduced RTP801 expression in the retina, consistent with the
      RNA-induced silencing complex (RISC) mechanism of action. The pharmacodynamic
      profile from the animal models could be useful to elucidate dose and exposure
      dependency of RTP801 expression inhibition by siRNA.

PMID- 24458147
TI  - Vascular associations and dynamic process motility in perivascular myeloid cells
      of the mouse choroid: implications for function and senescent change.
AB  - PURPOSE: Immune and vascular alterations in the choroid are implicated in age
      related macular degeneration (AMD). As choroidal immune cells are incompletely
      understood with regard to their physiology and interactions with choroidal
      vessels, we examined the associations between myeloid and vascular components of
      the choroid in young and aged mice. METHODS: Albino CX3CR1(GFP/+) transgenic
      mice, whose choroidal myeloid cells possess green fluorescence, were perfused
      intraluminally with the vital dye DiI to label choroidal vessels. The
      distribution, morphology, behavior, and vascular associations of resident myeloid
      cells were examined using time-lapse live confocal imaging and
      immunohistochemical analysis. RESULTS: Dendritiform myeloid cells, comprising
      most of the resident immune cell population in the choroid, were widely
      distributed across the choroid and demonstrated close associations with choroidal
      vessels that varied with their position in the vascular tree. Notably, myeloid
      cells associated with choroidal arteries and arterioles appeared as elongated
      cells flanking the long axes of vessels, whereas those associated with the
      choriocapillaris were distributed as a layer of stellate cells on the scleral but
      not vitreal choriocapillaris surface. While stationary in position, dendritiform
      myeloid cells demonstrated the rapid process dynamism well suited to
      comprehensive immunosurveillance of the perivascular space. Myeloid cells also
      increased in density as a function of aging, correlating locally with greater
      choroidal vascular attenuation. CONCLUSIONS: Resident myeloid cells demonstrated
      close but dynamic physical interactions with choroidal vessels, indicative of
      constitutive immune-vascular interactions in the normal choroid. These
      interactions may alter progressively with aging, providing a basis for
      understanding age-related choroidal dysfunction underlying AMD.

PMID- 24458148
TI  - A nicotinic acetylcholine receptor agonist prevents loss of retinal ganglion
      cells in a glaucoma model.
AB  - PURPOSE: The purpose of this study was to analyze the neuroprotective effect of
      an alpha7 nAChR agonist, PNU-282987, using an in vivo model of glaucoma in Long
      Evans rats. METHODS: One eye in each animal was surgically manipulated to induce
      glaucoma in control untreated animals and in animals that were treated with
      intravitreal injections of PNU-282987. To induce glaucoma-like conditions, 0.05
      mL of 2 M NaCl was injected into the episcleral veins of right eyes in each rat
      to create scar tissue and increase intraocular pressure. The left eye in each rat
      acted as an internal control. One month following NaCl injection, rats were
      euthanized, retinas were removed, flatmounted, fixed, and nuclei were stained
      with cresyl violet or RGCs were immunostained with an antibody against Thy 1.1 or
      against Brn3a. Stained nuclei in the RGC layer and labeled RGCs in NaCl-injected
      retinas were counted and compared with cell counts from untreated retinas in the
      same animal. RESULTS: NaCl injections into the episcleral veins caused a
      significant loss of cells by an average of 27.35% (+/- 2.12 SEM) in the RGC layer
      within 1 month after NaCl injection, which corresponded to a significant loss of
      RGCs. This loss of RGCs was eliminated if 5 MUL of 100 MUM PNU-282987 was
      injected into the right eye an hour before NaCl injection. CONCLUSIONS: The
      results from this study support the hypothesis that the alpha7 agonist, PNU
      282987, has a neuroprotective effect in the rat retina. PNU-282987 may be a
      viable candidate for future therapeutic treatments of glaucoma.

PMID- 24458149
TI  - The safety, pharmacokinetics, and efficacy of intraocular celecoxib.
AB  - PURPOSE: To determine safety, pharmacokinetics, and anti-inflammatory effects of
      intraocular celecoxib. METHODS: The right eye of animals was injected with 1.5,
      3, or 6 mg celecoxib prepared in dimethyl sulfoxide (DMSO). Left eyes served as
      controls and received 0.1 mL DMSO. Electroretinograms (ERG) were obtained at
      baseline and at 1, 4, and 12 weeks, and eyes were enucleated afterward for
      histopathologic analysis. For pharmacokinetics, 3 mg celecoxib was injected, and
      vitreous and retina/choroid drug levels were then analyzed at specific time
      points. For efficacy, 1 MUg lipopolysaccharide was injected to induce
      inflammation; the right eye was then injected with 3 mg celecoxib (six eyes) or 2
      mg triamcinolone acetonide (six eyes) and the left eye with saline. Twenty-four
      hours later, aqueous fluid was removed, and total leukocyte concentration and
      prostaglandin E2 (PGE2) concentration were determined. RESULTS: Histologic and
      ERG studies demonstrated no signs of retinal or optic nerve toxicity. After a
      single 3-mg injection, vitreous (0.06 MUg/mL) and retina/choroid (132.31 MUg/g)
      celecoxib concentrations at 8 weeks exceeded median inhibitory concentration.
      Treatment with celecoxib and triamcinolone significantly reduced total leukocyte
      count by 40% (P = 0.02) and 31% (P = 0.01), respectively. Reduction in PGE2
      levels paralleled reduction in leukocyte counts (P < 0.05). There was no increase
      in intraocular pressure, but cataract formation was observed at higher
      concentrations. CONCLUSIONS: Intraocular injection of celecoxib appeared to be
      nontoxic and demonstrated excellent penetration into the retina/choroid and
      sustained drug levels out to 8 weeks. Celecoxib demonstrated potent anti
      inflammatory effects, but there was an association with cataract formation at
      higher doses.

PMID- 24458150
TI  - Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated
      mitochondrial alteration in a mouse model of glaucoma.
AB  - PURPOSE: To test whether a diet supplemented with coenzyme Q10 (CoQ10)
      ameliorates glutamate excitotoxicity and oxidative stress-mediated retinal
      ganglion cell (RGC) degeneration by preventing mitochondrial alterations in the
      retina of glaucomatous DBA/2J mice. METHODS: Preglaucomatous DBA/2J and age
      matched control DBA/2J-Gpnmb(+) mice were fed with CoQ10 (1%) or a control diet
      daily for 6 months. The RGC survival and axon preservation were measured by Brn3a
      and neurofilament immunohistochemistry and by conventional transmission electron
      microscopy. Glial fibrillary acidic protein (GFAP), superoxide dismutase-2
      (SOD2), heme oxygenase-1 (HO1), N-methyl-d-aspartate receptor (NR) 1 and 2A, and
      Bax and phosphorylated Bad (pBad) protein expression was measured by Western blot
      analysis. Apoptotic cell death was assessed by TUNEL staining. Mitochondrial DNA
      (mtDNA) content and mitochondrial transcription factor A (Tfam)/oxidative
      phosphorylation (OXPHOS) complex IV protein expression were measured by real-time
      PCR and Western blot analysis. RESULTS: Coenzyme Q10 promoted RGC survival by
      approximately 29% and preserved the axons in the optic nerve head (ONH), as well
      as inhibited astroglial activation by decreasing GFAP expression in the retina
      and ONH of glaucomatous DBA/2J mice. Intriguingly, CoQ10 significantly blocked
      the upregulation of NR1 and NR2A, as well as of SOD2 and HO1 protein expression
      in the retina of glaucomatous DBA/2J mice. In addition, CoQ10 significantly
      prevented apoptotic cell death by decreasing Bax protein expression or by
      increasing pBad protein expression. More importantly, CoQ10 preserved mtDNA
      content and Tfam/OXPHOS complex IV protein expression in the retina of
      glaucomatous DBA/2J mice. CONCLUSIONS: Our findings suggest that CoQ10 may be a
      promising therapeutic strategy for ameliorating glutamate excitotoxicity and
      oxidative stress in glaucomatous neurodegeneration.

PMID- 24458151
TI  - A novel association between resident tissue macrophages and nerves in the
      peripheral stroma of the murine cornea.
AB  - PURPOSE: To characterize the interactions between resident macrophage populations
      and nerves in naive and injured corneas of the mouse eye. METHODS: Corneas from
      wild-type (WT) C57BL/6J, BALB/cJ, and transgenic Cx3cr1-eGFP mice were subjected
      to a 1-mm central epithelial debridement injury. The eyes were fixed and
      immunostained as flat mounts with a range of antibodies to identify macrophages,
      neurons, and Schwann cells. Interactions between nerves and immune cells were
      analyzed and quantitated using three-dimensional reconstructions of confocal
      microscopy images. Naive eyes acted as controls. RESULTS: A distinctive
      association between resident immune cells and corneal nerves was noted in the
      peripheral or perilimbal stromal nerve trunks. These epineurial cells were mostly
      Cx3cr1(+) Iba-1(+) major histocompatibility complex (MHC) class II(+) F4/80(+)
      CD11b(+) macrophages. The number of nerve-associated macrophages was greater in
      WT BALB/c mice than in C57BL/6J mice. There were no qualitative or quantitative
      differences in the circumferential distribution of nerve-associated macrophages
      in the cornea. Sterile corneal epithelial debridement led to a dissociation of
      macrophages from peripheral nerve trunks as early as 2 hours postinjury, with
      numbers returning to baseline after 72 hours. This dissociation was Cx3cr1
      dependent. CONCLUSIONS: This study is the first to highlight a direct physical
      association between nerves and resident immune cells in the murine cornea.
      Furthermore, we reveal that this association in normal eyes is responsive to
      central corneal epithelial injury and is partly mediated by Cx3cr1 signaling.
      This association may serve as an indicator of malfunctioning neuroimmune
      communication in disease states such as neurotrophic keratitis and peripheral
      neuropathy.

PMID- 24458152
TI  - OCT evaluation of neuroprotective effects of tafluprost on retinal injury after
      intravitreal injection of endothelin-1 in the rat eye.
AB  - PURPOSE: To determine whether optical coherence tomography (OCT) is a useful
      technique to monitor retinal damage and to evaluate the neuroprotective effect of
      topical tafluprost in a rat model of intravitreal endothelin-1 (ET-1) injection.
      METHODS: A single intravitreal injection of ET-1 (0.2-200 pmol/eye) was performed
      in one eye. Optical coherence tomography imaging was performed until 2 weeks
      after ET-1 injection. Subsequently, an intravitreal injection of ET-1 (20
      pmol/eye) was performed in one eye of each rat, which was followed by topical
      instillation of tafluprost or saline once daily for 4 weeks. Optical coherence
      tomography imaging was performed until 4 weeks after ET-1 injection. After the
      last OCT session, retinal ganglion cells (RGCs) were retrogradely labeled with
      Fluorogold. RESULTS: Endothelin-1 at doses of 20 to 200 pmol/eye caused a
      significant decrease in inner retinal thickness, whereas ET-1 at doses of 0.2 to
      5 pmol/eye did not. The inner retinal thickness at 2 weeks postinjection was
      strongly correlated with Fluorogold-labeled RGC counts in the central retina (r =
      0.92, P < 0.001). The inner retina of eyes treated with tafluprost was
      significantly thicker than eyes treated with saline at 1 and 2 weeks (P = 0.038
      and P = 0.045, respectively). Fluorogold-labeled RGC counts in the central retina
      of eyes treated with tafluprost were significantly greater than in eyes treated
      with saline (P = 0.03). CONCLUSIONS: Optical coherence tomography is useful for
      monitoring inner retinal damage in a rat model of intravitreal ET-1 injection.
      Daily topical administration of tafluprost may be protective against ET-1-induced
      retinal injury in the rat.

PMID- 24458153
TI  - A model for tear film thinning with osmolarity and fluorescein.
AB  - PURPOSE: We developed a mathematical model predicting dynamic changes in
      fluorescent intensity during tear film thinning in either dilute or quenching
      regimes and we model concomitant changes in tear film osmolarity. METHODS: We
      solved a mathematical model for the thickness, osmolarity, fluorescein
      concentration, and fluorescent intensity as a function of time, assuming a flat
      and spatially uniform tear film. RESULTS: The tear film thins to a steady-state
      value that depends on the relative importance of the rates of evaporation and
      osmotic supply, and the resulting increase of osmolarity and fluorescein
      concentrations are calculated. Depending on the initial thickness, the rate of
      osmotic supply and the tear film thinning rate, the osmolarity increase may be
      modest or it may increase by as much as a factor of eight or more from isosmotic
      levels. Regarding fluorescent intensity, the quenching regime occurs for initial
      concentrations at or above the critical fluorescein concentration where
      efficiency dominates, while lower concentrations show little change in
      fluorescence with tear film thinning. CONCLUSIONS: Our model underscores the
      importance of using fluorescein concentrations at or near the critical
      concentration clinically so that quenching reflects tear film thinning and
      breakup. In addition, the model predicts that, depending on tear film and osmotic
      factors, the osmolarity within the corneal compartment of the tear film may
      increase markedly during tear film thinning, well above levels that cause marked
      discomfort.

PMID- 24458154
TI  - Baseline prognostic factors predict rapid visual field deterioration in glaucoma.
AB  - PURPOSE: To investigate baseline prognostic factors predicting rapid
      deterioration of the visual field in primary open-angle glaucoma patients.
      METHODS: Seven hundred sixty-seven eyes of 566 glaucoma patients from the
      Advanced Glaucoma Intervention Study (AGIS) and the clinical database from Jules
      Stein Eye Institute's Glaucoma Division were included. The rates of decay at each
      visual field test location were calculated with pointwise exponential regression
      analysis (PER), and the rates were separated into faster and slower components
      for each series. Subjects with a faster component decay rate (>= 36%/y) were
      defined as rapid progressors. Sex, race, age, visual acuity, intraocular
      pressure, mean deviation (MD), number of medications, use of diabetic or
      hypertension medications, and vertical cup-to-disc ratio at baseline were entered
      in a multivariable prognostic logistic regression model. RESULTS: The average (+/
      SD) MD was -8.02 (+/- 6.13), and the average age was 68.64 (+/- 11.71) years for
      the study group. Two hundred twenty-two eyes (28.9%) were identified as rapid
      progressors. The following baseline factors were predictors of faster
      deterioration: worse MD (P < 0.001, odds ratio [OR]: 1.11; 95% confidence
      interval [CI]: 1.07-1.15), larger vertical cup-to-disc ratio (P = 0.001, OR:
      1.23; 95% CI: 1.09-1.39), and older age (P = 0.02, OR: 1.24; 95% CI: 1.04-1.48).
      After excluding the variables related to glaucoma severity at baseline (baseline
      MD and baseline vertical cup-to-disc ratio), the likelihood of being a rapid
      progressor was 54% greater in African Americans than in Caucasians (P = 0.03, OR:
      1.55; 95% CI: 1.06-2.27). CONCLUSIONS: Patients with more severe glaucomatous
      damage, as measured by both visual field or optic disc cupping and older age, are
      at highest risk for rapid worsening of the disease, as are African Americans
      compared to Caucasians. More aggressive treatment of such patients should be
      considered to prevent visual disability.

PMID- 24458155
TI  - Noninvasive imaging of retinal morphology and microvasculature in obese mice
      using optical coherence tomography and optical microangiography.
AB  - PURPOSE: To evaluate early diabetes-induced changes in retinal thickness and
      microvasculature in a type 2 diabetic mouse model by using optical coherence
      tomography (OCT)/optical microangiography (OMAG). METHODS: Twenty-two-week-old
      obese (OB) BTBR mice (n = 10) and wild-type (WT) control mice (n = 10) were
      imaged. Three-dimensional (3D) data volumes were captured with spectral domain
      OCT using an ultrahigh-sensitive OMAG scanning protocol for 3D volumetric
      angiography of the retina and dense A-scan protocol for measurement of the total
      retinal blood flow (RBF) rate. The thicknesses of the nerve fiber layer (NFL) and
      that of the NFL to the inner plexiform layer (IPL) were measured and compared
      between OB and WT mice. The linear capillary densities within intermediate and
      deep capillary layers were determined by the number of capillaries crossing a 500
      MUm line. The RBF rate was evaluated using an en face Doppler approach. These
      quantitative measurements were compared between OB and WT mice. RESULTS: The
      retinal thickness of the NFL to IPL was significantly reduced in OB mice (P <
      0.01) compared to that in WT mice, whereas the NFL thickness between the two was
      unchanged. 3D depth-resolved OMAG angiography revealed the first in vivo 3D model
      of mouse retinal microcirculation. Although no obvious differences in capillary
      vessel densities of the intermediate and deep capillary layers were detected
      between normal and OB mice, the total RBF rate was significantly lower (P < 0.05)
      in OB mice than in WT mice. CONCLUSIONS: We conclude that OB BTBR mice have
      significantly reduced NFL-IPL thicknesses and total RBF rates compared with those
      of WT mice, as imaged by OCT/OMAG. OMAG provides an unprecedented capability for
      high-resolution depth-resolved imaging of mouse retinal vessels and blood flow
      that may play a pivotal role in providing a noninvasive method for detecting
      early microvascular changes in patients with diabetic retinopathy.

PMID- 24458156
TI  - Age-related changes of cystatin C expression and polarized secretion by retinal
      pigment epithelium: potential age-related macular degeneration links.
AB  - PURPOSE: Cystatin C, a potent cysteine proteinase inhibitor, is abundantly
      secreted by the RPE and may contribute to regulating protein turnover in the
      Bruch's membrane (BrM). A cystatin C variant associated with increased risk of
      developing AMD and Alzheimer's disease (AD) presents reduced secretion levels
      from RPE. The purpose of this study was to analyze the effects of age and the
      accumulation of advanced glycation end-products (AGEs) on the expression and
      secretion of cystatin C by the RPE. METHODS: Confluent monolayers of human fetal
      RPE (hfRPE) cells were cultured using an in vitro model mimicking extracellular
      AGE accumulation. Cystatin C expression, secretion, and its polarity were
      analyzed following culture on AGE-containing BrM mimics (AGEd versus non-AGEd).
      Monolayer barrier properties were assessed by transepithelial resistance
      measurements. The relative level of cystatin C protein expression in human RPE in
      situ was assessed immunohistochemically in relation to age. RESULTS: Advanced
      glycation end product-exposed RPE monolayers presented significantly decreased
      cystatin C expression and secretion. Basolateral secretion was fully established
      by week 8 in non-AGEd conditions. In AGEd cultures, polarity of secretion was
      impaired despite maintenance of physiological barrier properties of the
      monolayer. In the macula region of RPE/choroid segments from human eyes, the
      level of cystatin C protein was reduced with increasing donor age. CONCLUSIONS:
      Exposure to AGEs reduces expression of cystatin C and affects its normal
      secretion in cultured RPE. Age-related changes of cystatin C in the RPE from the
      posterior pole may compromise its extracellular functions, potentially
      contributing to AMD pathogenesis.

PMID- 24458157
TI  - Variations of retinal nerve fiber layer thickness and ganglion cell-inner
      plexiform layer thickness according to the torsion direction of optic disc.
AB  - PURPOSE: To examine the relationship between the optic disc torsion and
      peripapillary retinal nerve fiber layer (RNFL) thickness through a comparison
      with the macular ganglion cell inner plexiform layer complex (GCIPL) thickness
      measured by Cirrus optical coherence tomography (OCT). METHODS: Ninety-four eyes
      of 94 subjects with optic disc torsion and 114 eyes of 114 subjects without optic
      disc torsion were enrolled prospectively. The participants underwent fundus
      photography and OCT imaging in peripapillary RNFL mode and macular GCIPL mode.
      The participants were divided into groups according to the presence or absence of
      optic disc torsion. The eyes with optic disc torsion were further divided into
      supranasal torsion and inferotemporal torsion groups according to the direction
      of optic disc torsion. The mean RNFL and GCIPL thicknesses for the quadrants and
      subsectors were compared. The superior and inferior peak locations of the RNFL
      were also measured according to the torsion direction. RESULTS: The temporal RNFL
      thickness was significantly thicker in inferotemporal torsion, whereas the GCIPL
      thickness at all segments was unaffected. The inferotemporal optic torsion had
      more temporally positioned superior peak locations of the RNFL than the
      nontorsion and supranasal-torted optic disc. CONCLUSIONS: Thickening of the
      temporal RNFL with a temporal shift in the superior peak within the eyes with
      inferotemporal optic disc torsion can lead to interpretation errors. The ganglion
      cell analysis algorithm can assist in differentiating eyes with optic disc
      torsion.

PMID- 24458159
TI  - A compact trench-assisted multi-orbital-angular-momentum multi-ring fiber for
      ultrahigh-density space-division multiplexing (19 rings * 22 modes).
AB  - We present a compact (130 MUm cladding diameter) trench-assisted multi-orbital
      angular-momentum (OAM) multi-ring fiber with 19 rings each supporting 22 modes
      with 18 OAM ones. Using the high-contrast-index ring and trench designs, the
      trench-assisted multi-OAM multi-ring fiber (TA-MOMRF) features both low-level
      inter-mode crosstalk and inter-ring crosstalk within a wide wavelength range
      (1520 to 1630 nm), which can potentially enable Pbit/s total transmission
      capacity and hundreds bit/s/Hz spectral efficiency in a single TA-MOMRF.
      Moreover, the effective refractive index difference of even and odd fiber
      eigenmodes induced by the ellipticity of ring and fiber bending and their impacts
      on the purity of OAM mode and mode coupling/crosstalk are analyzed. It is found
      that high-order OAM modes show preferable tolerance to the ring ellipticity and
      fiber bending. The designed fiber offers favorable tolerance to both small
      ellipticity of ring (<-22 dB crosstalk under an ellipticity of 0.5%) and small
      bend radius (<-20 dB crosstalk under a bend radius of 2 cm).

PMID- 24458158
TI  - Aquaporin-0 targets interlocking domains to control the integrity and
      transparency of the eye lens.
AB  - PURPOSE: Lens fiber cell membranes contain aquaporin-0 (AQP0), which constitutes
      approximately 50% of the total fiber cell membrane proteins and has a dual
      function as a water channel protein and an adhesion molecule. Fiber cell
      membranes also develop an elaborate interlocking system that is required for
      maintaining structural order, stability, and lens transparency. Herein, we used
      an AQP0-deficient mouse model to investigate an unconventional adhesion role of
      AQP0 in maintaining a normal structure of lens interlocking protrusions. METHODS:
      The loss of AQP0 in AQP0(-/-) lens fibers was verified by Western blot and
      immunofluorescence analyses. Changes in membrane surface structures of wild-type
      and AQP0(-/-) lenses at age 3 to 12 weeks were examined with scanning electron
      microscopy. Preferential distribution of AQP0 in wild-type fiber cell membranes
      was analyzed with immunofluorescence and immunogold labeling using freeze
      fracturing transmission electron microscopy. RESULTS: Interlocking protrusions in
      young differentiating fiber cells developed normally but showed minor
      abnormalities at approximately 50 MUm deep in the absence of AQP0 in all ages
      studied. Strikingly, protrusions in maturing fiber cells specifically underwent
      uncontrolled elongation, deformation, and fragmentation, while cells still
      retained their overall shape. Later in the process, these changes eventually
      resulted in fiber cell separation, breakdown, and cataract formation in the lens
      core. Immunolabeling at the light microscopy and transmission electron microscopy
      levels demonstrated that AQP0 was particularly enriched in interlocking
      protrusions in wild-type lenses. CONCLUSIONS: This study suggests that AQP0
      exerts its primary adhesion or suppression role specifically to maintain the
      normal structure of interlocking protrusions that is critical to the integrity
      and transparency of the lens.

PMID- 24458160
TI  - Preoperative FDG-PET-scan in patients with resectable colorectal liver metastases
      does not improve overall survival: a retrospective analyses stratified by
      clinical risk score.
AB  - BACKGROUND: The aim of this study was to determine whether selection with
      fluorine-18-deoxyglucose positron emission tomography (FDG-PET) imaging would
      result in an improved outcome in surgically treated patients with curative
      resection of colorectal liver metastases (CRLM), stratified by the clinical risk
      score (CRS) of Fong et al. [Ann Surg 1999;230:309-318]. PATIENTS AND METHODS:
      Between January 2000 and December 2009, all patients who underwent resection for
      CRLM from two different university teaching hospitals in the Netherlands were
      analysed. Patients were stratified by the CRS. RESULTS: In total 613 patients
      were eligible for analysis. There was no statistical difference in median disease
      free survival (DFS) between patients with and without an FDG-PET scan in both low
      CRS [17 months (95% CI 12-22) vs. 14 months (95% CI 11-17), p = 0.332] and high
      CRS [14 months (95% CI 7-21) vs. 9 months (95% CI 8-10), p = 0.073]. There was no
      statistical difference in median overall survival (OS) between patients with and
      without an FDG-PET scan in both low CRS [64 months (95% CI 54-74) vs. 54 months
      (95% CI 42-66), p = 0.663] and high CRS [39 months (95% CI 23-55) vs. 41 months
      (95% CI 34-48), p = 0.903]. CONCLUSION: The present study could not demonstrate
      that patients selected by an FDG-PET scan before liver resection, and stratified
      by CRS, have an improvement in DFS or OS.

PMID- 24458161
TI  - Volume-outcome relationship in colon cancer surgery: another biased logical short
      cut towards questionable centralization policies.
AB  - The association between hospital high volumes and good outcomes after complex
      surgery has given rise to a worldwide controversial debate. Important and
      unsolved questions have followed, both theoretical and practical, which could
      have repercussions on health care and health economic policies, such as the
      centralization/regionalization of major surgical procedures.We read a recent
      study on the impact of surgery volumes on short-term outcomes after colon cancer
      resection in Emilia Romagna, Italy, the same geographic area where we operate.
      Ten issues were submitted to critical analysis and many sources of planning and
      methodology bias were identified, which, in our opinion, paradigmatically led to
      unreliable results, inadequate statistical analysis and deceptive conclusions.
      Despite the authors' admitted awareness of their study's limits, their conclusive
      message was, surprisingly, that centralization of colon cancer surgery should be
      substantially encouraged.Unrecognized, systemic biases may easily turn into
      cognitive biases, into logical short cuts which could confuse healthcare policy
      makers. The volume-outcome relationship, in which a direct causal link has never
      been demonstrated, should not be used as a reliable measure of quality, rather 
      than less implementable process indicators, to address centralization policies.A
      disregarded negative consequence of centralization could be that non-high-volume
      centres, after a further progressive workload decrease and depletion in resources
      and surgical skills, will have to cope with patients in bad general condition and
      at high risk, who must be treated in emergency or cannot anyway afford the move
      for age, indigence or severe co-morbidities. Thus, centralization policies might
      disadvantage the weak segments of the population, thereby moving towards an
      iniquitous health service.

PMID- 24458162
TI  - "GIOCAMPUS" - An effective school-based intervention for breakfast promotion and
      overweight risk reduction.
AB  - The aim of this study was to evaluate the efficacy of a campaign promoting
      breakfast in primary school-children from the city of Parma, Italy, where 22 % of
      peer school-children had reported in 2005 to  skip breakfast. Two groups of
      children were interviewed by a multiple choice questionnaire on their breakfast
      habits. Group 1 counted only the children who  underwent the intensive campaign
      (n. 341), and  Group 2 a number of matched peers who did not attend any breakfast
      promoting program (n. 291). Children who did not eat breakfast were found to be
      more numerous in Group 2 (17.5 %) than in  Group 1 (8.0 %; p=0.0001). In the
      Group 2 the percentage of  overweight (18.4 %) was higher compared to Group 1
      patients (11.7 %; p=0.022). No significant difference in obesity percentage (8.9
      vs 5.0 %; p=0.071).  Seventy five percent of children in Group I and the 25% of
      children in Group 2 (p=0.031) had one or two parents who had reported to skip
      routinely breakfast. Children with one or both parents used to skip breakfast had
      a greater odds ratio of 3.04  and  3 respectively of skipping breakfast compared
      to the children  with parents who had regularly  breakfast (p=0.0002). Compared
      to the children tested in 2005,  children admitted to   the Giocampus program
      showed: a significant decrease in breakfasting (22 vs 8 %; p=0.0001), a
      significant decrease in overweight (18.5 vs 11.7 %; p=0.003) but not in obesity
      (7.5 vs 5.0 %; p=0.138) status; a significant increase in consumption of cereals
      (p=0.0001) and fruit (p=0.0001). In conclusion, an intensive breakfast-centred
      strategy seems to be effective in breakfast promotion and in overweight risk
      decrease. 

PMID- 24458163
TI  - Teicoplanin as an anti-methicillin resistant Staphylococcus aureus agent in
      infections of severely poisoned intensive care unit patients/ Tehran- Iran.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is
      related to high morbidity and mortality. Glycopeptide antibiotic is the choice of
      treatment in MRSA infections. Teicoplanin is a semi synthetic glycopeptide
      antibiotic with a spectrum of activity similar to vancomycin.  Our objective is
      the evaluation of efficacy and safety of Teicoplanin in MRSA infections among
      severely poisoned intensive care unit (ICU) patients. METHOD: During a 6 months
      period, in a prospective cross sectional study 54 eligible patients from 80
      clinically suspicious with MRSA infections were recruited. The efficacy and
      safety of Teicoplanin was evaluated 5 times. The clinical findings, laboratory
      data, and bacteriologic responses were defined as cure, improvement and failure.
      RESULTS: The mean age of the patients was 36.3 years (range, 20-72, SD = 13.3).
      75.9% were male. Suicidal attempts were recorded in 63%. The most common
      poisoning was TCAs, BZDs, tramadol and opium. 94.4% were unconscious and under
      mechanical ventilation. Tracheal cultures were positive in 98.1% by VAP
      diagnosis. Length of stay in the ICU was between  4-54 days. Total clinical
      effectiveness was 90.4%, and failure 9.6%. Mortality rate of the patient, was
      9/54 (16.6 %) which 3 of them were for lack of a clinical response. On the fourth
      visit, the adverse effects included: rash (11.10%), anemia (36.17%),
      nephrotoxicity (17.02%) and thrombocytopenia < 150000 (100%). Other side effects
      such as: leucopenia, severe thrombocytopenia (< 50000), pancytopenia and red man
      syndrome were not detected. CONCLUSIONS: Teicoplanin is suggestible for MRSA
      infections among severely poisoned patients according to its efficacy, safety,
      half life and tolerance.

PMID- 24458164
TI  - Medial neck femoral fractures: algorithm of treatment and the use of f.g.L. TM
      memory shape stem.
AB  - BACKGROUND AND AIM OF THE WORK: We treat undisplaced or minimally displaced
      medial neck femoral fractures with screws in both young and elderly patients with
      good activity of daily living, without severe comorbidity. Total hip replacement
      is preferred in middle-advanced age, with good level of functional activity.
      Bipolar hemiarthroplasty is performed on patients who may require early
      mobilization to avoid deterioration due to existing comorbidities. Bipolar
      hemiarthroplasty with memory shape stem  (F.G.L.TM) is our preferred mode of
      surgery for high risk patients (ASA classification). In fact, higher
      perioperative mortality from cardiopulmonary complications has been attributed to
      the use of cement during arthroplasty. This stem in its metaphyseal region has 10
      tabs, made of a NitinolTM alloy, that facilitate the restoration of the implant
      to its original enlarged shape at physiological temperature. This enables a
      strong fit in the metaphyseal region. METHODS: We report the clinical and
      radiological results of 24 patients (mean follow-up: 14 months) who underwent
      surgical procedure of bipolar hemiarthroplasty with F.G.L.TM stem in our
      department between March 2008 and December 2009. RESULTS: No perioperative
      complications were observed and the results were comparable to those of patients
      who underwent standard cemented bipolar hemiarthroplasty. CONCLUSIONS: A
      significant advantage to the use of F.G.L.TM stem is that it allows immediate
      primary stability without using cement. A limiting consideration is the higher
      cost associated with the implant & procedure in comparison with standard cemented
      bipolar hemiarthroplasty. This implant may thus be most suitable for patients
      with pre-existing cardio-pulmonary complications for whom the use of cement is a
      major risk factor.

PMID- 24458165
TI  - Plating in diaphyseal fractures of the forearm.
AB  - BACKGROUND AND AIM OF THE WORK: Currently, open reduction and internal plate
      screw fixation is generally accepted as the gold standard treatment of diaphyseal
      forearm fractures. The purpose of this retrospective study was to evaluate the
      clinical and radiographic outcomes of open reduction and internal fixation by
      using the Locking Compression Plate (LCP) implant system of radial, ulnar or
      combined shaft fractures of a skeletally mature patients group treated at our
      institution. METHODS: We examined 47 patients, 44 men and 3 women, mean age 35
      years (range 14-74) operated for diaphyseal fractures of the forearm. Overall 64
      segments were treated: 32 ulnar and 32 radial. All patients received 3.5-mm
      titanium LCPs (Locking Compression Plates) with "combi-holes". Follow-ups
      included standard X-rays and clinical assessment according to Anderson's criteria
      and the DASH questionnaire. RESULTS: Mean follow-up was 11 months (range 6-39).
      The number of the patients who achieved complete consolidation was 43 with a
      union rate of 91.5%. They showed 37 excellent results and 6 satisfactory results
      according to Anderson criteria, while non-union occurred in 4 out of 64 segments
      (2 ulnar and 2 radial) with a non-union rate per patient of 8,5%. The mean score
      of the DASH scale was 13.5 (range 0-46.7). CONCLUSIONS: Our data show that
      internal plating gives good functional outcomes in the treatment of forearm
      diaphyseal fractures, as long as the surgical technique is perfect and carried
      out by expert surgeons. However, further research is desirable to better identify
      fracture types for which LCPs should be used.

PMID- 24458166
TI  - Total elbow arthroplasty following traumas: mid-term results.
AB  - BACKGROUND: Total elbow arthroplasty (TEA) has been normally indicated for
      chronic inflammatory arthropathy. In the last decades this surgery has also
      evolved as an acceptable procedure following traumatic lesions of this joint. The
      aim of this study was to analyze the mid-term outcomes of TEA for the treatment
      of complex fractures and non-unions of the elbow in selected patients. METHODS:
      Between May 2002 and December 2011, 34 patients with these indications were
      surgically treated with TEA and divided in two groups. Group 1 included 16 cases
      of fractures and Group 2 18 of non-union. All patients were clinically assessed
      using the Mayo Elbow Performance Score (MEPS). A statistical analysis was
      performed in order to investigate the outcomes of these patients and compare the
      two groups. RESULTS: Similar results were observed in both groups between
      operated and non-operated arms. No differences in clinical results were
      documented between groups. CONCLUSIONS: TEA following traumas can be considered
      as a valid treatment in old patients in complex fractures of the elbow region
      with low functional demands and in non-unions. Outcomes are influenced by the
      collaborative capacities of the patients.

PMID- 24458167
TI  - Isolated fractures of the greater tuberosity in proximal humerus: does the
      direction of displacement influence functional outcome? An analysis of
      displacement in greater tuberosity fractures.
AB  - BACKGROUND AND AIM OF THE WORK: The treatment of isolated fractures of the
      greater tuberosity of the proximal humerus is still debated, especially in the
      case of minimally dispaced fractures. Differently from other proximal humerus
      fractures this kind of injury frequently affects young patients with high
      functional request. The aim of this study is to assess the outcome of patients
      treated conservatively for greater tubero-sity isolated fractures, comparing the
      clinical results in patients with different direction of fracture displacement.
      METHODS: 38 patients with isolated fracture of greater tuberosity participated to
      the study and were evaluated at 17 months (10-26) of follow up using Constant
      Murley Score and DASH Score. Patients were divided in groups with different
      direction of displacement (10 no displacement, 13 postero-superior, 6 antero
      superior and 9 antero-inferior displacement). RESULTS: Patients with no displaced
      fractures had a mean Constant Murley Score of 82 and a mean DASH Score of 15;
      those with postero-superior displacement had a mean a Constant Murley Score of 61
      and a mean DASH Score of 43; for antero-superior displacement the mean Constant
      Murley Score was 76 and the mean DASH Score of 18; for the antero-inferiorly
      displaced the mean Constant Murley Score was 83 and the DASH Score 16.
      CONCLUSION: Data suggest that postero-superior displacement leads to poorer
      outcomes than undisplaced or displaced in other directions fractures treated
      conservatively.

PMID- 24458169
TI  - Paravertebral block for patients older than 80 years in one day surgery elective
      mastectomy.
AB  - Paravertebral block (PVB) has been proposed as an alternative to General
      anaesthesia (GA) for breast surgery. It provides good operative anaesthesia, good
      pain control with little adverse effects. Six women older than 80 year were
      selected. All patients were post-operatively interviewed about the presence of
      pain, nausea and vomiting. All patients declared absence of pain and nausea and
      that they were satisfied with the procedure. The use of PVB allows elderly
      patients to undergo ambulatory surgery for the treatment of breast cancer with
      satisfaction. This technique allows a short recovery and adequate postoperative
      pain relief with reduced hospital costs. 

PMID- 24458168
TI  - Accidental mushroom poisoning mimicking stroke. A case report and literature
      review.
AB  - We describe here a paradigmatic case of mushroom poisoning mimicking a stroke. A
      64-year old male was referred to the emergency department (ED) for a car
      accident. He was found diaphoretic, hypotensive, bradycardic, and slightly
      confused at presentation. No signs of trauma were observed on physical
      examination. The patient had weakness of the right limbs and bilateral severe
      myosis. The lab tests were normal, except for leukocytosis, mild hyperglycemia,
      mild hyperazotemia and moderate hypokalemia. The clinical picture, with the
      exception of miosis, was thereby suggestive for a stroke, which was also
      considered the cause of the car accident. The patients' wife, who was brought
      later to the ED, reported that the husband had suffered a stroke 4 years earlier,
      with residual right hemiparesis. She also referred that the patient showed signs
      of diaphoresis and confusion, and the car was intentionally driven into the
      ditch. Among other details, she referred that the husband ate mushrooms that she
      had personally collected 2 hours before taking the drive. Two mg of atropine,
      intravenous rehydration and potassium were hence administered in the suspicion of
      a cholinergic toxydrome, and complete clinical remission was rapidly obtained.
      Among the mixture of mushrooms eaten by the patient, a mycologist identified
      Armillaria Mellea (an edible mushroom) and notably Inocybe Fastigiata, a toxic
      muscarine-containing mushroom, easily confounded with Armillaria. After
      observation and oral rehydration, the patient was discharged. 

PMID- 24458171
TI  - NAFLD: a sign of "early aging"?

PMID- 24458170
TI  - Return to run after partial amputation of the ankle: clinical assessment and
      instrumental evaluation.
AB  - BACKGROUND AND AIM OF THE WORK: the traumatic amputation or partial amputation of
      a portion of the lower limb is one of the most serious and not so rare road
      accident and job injury. There are few cases reported of replantation of the
      lower extremities rather than amputation surgery. This work describes a case of
      partial amputation of the right ankle. METHODS: the emergency treatment consisted
      of rigorous lavage and debridement, reduction, stabilization of the ankle and
      restoreation of the neurovascular and soft tissues lesions. Because of cutaneous
      necrosis another surgical treatment of reverse rotation flap was needed. The good
      outcome has been documented with foot pressure analysis, stabilometric evaluation
      and gait and jump analysis based on measurements of acceleration. RESULTS: after
      seven months of personalized rehabilitation program the patient walks without
      devices, has recovered functional of range of movement and had no neurological
      deficit or subjective problems. Currently the subject has returned to his job and
      runs without pain. CONCLUSIONS: emergency foot salvage treatment was possible
      thanks to a close collaboration among different physicians with specialized
      skills, good emergency management and an adequate infrastructure.

PMID- 24458172
TI  - The perception of the ageing process through time: historical highlights.

PMID- 24458173
TI  - Red ginseng relieves the effects of alcohol consumption and hangover symptoms in
      healthy men: a randomized crossover study.
AB  - Heavy drinking causes hangover symptoms, because the action of alcohol
      dehydrogenase forms acetaldehyde, which is metabolized by acetaldehyde
      dehydrogenase into acetate. Red ginseng shows positive effects on alcohol
      metabolism in animal studies. We investigated the effects of red ginseng on
      relieving alcohol and hangover symptoms in 25 healthy men in a randomized
      crossover study. At each visit (0, 1, and 2 weeks), the subjects drank 100 mL
      whiskey (40% alcohol) and either 100 mL water or 100 mL of a 0.321 mg mL(-1) red
      ginseng anti-hangover drink (RGD). We took blood samples periodically until 240
      min after alcohol consumption, and we investigated the blood profiles, alcohol
      levels, and acetaldehyde levels. We also measured anthropometric parameters,
      expiratory air-alcohol levels, and hangover symptoms. The plasma alcohol
      concentrations within the RGD group were significantly lower than those within
      the placebo group after 30 min (p = 0.002), 45 min (p = 0.016), and 60 min (p =
      0.009); the areas under the response curves revealed a positive effect of RGD (p
      = 0.051). Furthermore, the expiratory alcohol concentration was significantly
      lower after 30 min (p = 0.005) and 60 min (p = 0.065), and the areas under the
      response curves (p = 0.058) likewise revealed a positive effect of RGD. The
      plasma acetaldehyde level was significantly elevated at 120 min (p = 0.020), but
      the areas under the response curves showed a similar trend (p = 0.054). While the
      plasma acetaldehyde concentration slightly increased, the RGD showed positive
      effects on hangover symptoms. Considering the reduction of plasma alcohol levels,
      expiratory concentrations, and hangover severity, we conclude that red ginseng
      relieves the symptoms of alcohol hangover. 

PMID- 24458174
TI  - Retroperitoneal pheochromocytoma with thorax and bilateral neck chemodectoma in
      patients with multiorgan sarcoidosis.
AB  - A 37-year-old man with multiorgan sarcoidosis, hypertension, and abdominal mass
      on CT was referred to the nuclear medicine department. PET/CT with 68Ga DOTATATE
      demonstrated an increased uptake in the abdominal mass and in the mediastinum,
      neck (bilaterally), and right jugular foramen; low uptake was observed in hilar
      and groin lymph nodes. MRI revealed abnormal focal lesions, showing increased
      signal on T2-weighted fat-saturated images, marked contrast enhancement on T1
      weighted gradient-echo images, and restricted diffusion in the same locations as
      on PET/CT. Patients underwent surgery of abdominal mass and right neck tumors,
      with histologic diagnosis consistent with extra-adrenal pheochromocytoma and neck
      chemodectoma.

PMID- 24458175
TI  - Mirror-image lymph node in FDG PET/CT and SPECT/CT for sentinel node detection.
AB  - We report a case of a patient with presumed stage IB1 squamous cell carcinoma of
      the cervix in which FDG PET/CT scan revealed 1 hypermetabolic left iliac node
      suggestive to be malignant. Lymphoscintigraphy and SPECT/CT studies previous to
      sentinel node (SLN) biopsy revealed unilateral drainage in the right pelvis.
      Intraoperative pathological assessment of the SLN showed no tumoral involvement,
      and the hypermetabolic node revealed macrometastasis. Tumor node invasion can
      lead to a lymphatic blockage and become false-negative for SLN technique.
      Although FDG PET/CT has lower sensitivity than surgical staging, this case shows
      its value as a preoperative imaging technique. 

PMID- 24458176
TI  - Recurrent parathyroid carcinoma appearing as FDG negative but MIBI positive.
AB  - A 44-year-old woman with recurrent parathyroid carcinoma (PTC) presents with
      moderately elevated parathyroid hormone and ionized calcium levels. Dual-phase Tc
      MIBI SPECT study of the neck and chest demonstrated 2 new foci in keeping with
      neoplastic seeding. A restaging whole-body F-FDG PET/CT showed no evidence of FDG
      uptake in the region of the MIBI-positive foci or any evidence of distant
      metastases. The role of F-FDG PET/CT for imaging PTC is still somewhat limited
      because of the rarity of this disease. We present a case highlighting a potential
      pitfall for FDG PET in detecting PTC. 

PMID- 24458177
TI  - Diffuse renal parenchyma uptake with bone scintigraphy in a patient with
      paroxysmal nocturnal hemoglobinuria and normal kidney function.
AB  - A 41-year-old woman with a Harrington spondylodesis presented with lower back
      pain. Bone scintigraphy showed diffusely increased parenchymal uptake in both
      kidneys. She reported 2 previous periods of dark, almost black, urine. Additional
      flow cytometric analysis confirmed the diagnosis of paroxysmal nocturnal
      hemoglobinuria. The increased renal parenchyma uptake is very probably due to
      paroxysmal nocturnal hemoglobinuria-related renal hemosiderosis. Remarkably, the
      patient did not develop any abnormality of renal function. 

PMID- 24458178
TI  - FDG PET/CT findings in a rare case of giant fibrovascular polyp of the esophagus
      harboring atypical lipomatous tumor/well-differentiated liposarcoma.
AB  - A 70-year-old man with a history of chronic lymphocytic leukemia (CLL) underwent
      FDG PET/CT scan, which revealed a large polypoid soft tissue lesion in the
      esophagus with peripheral FDG avidity. An endoscopic biopsy revealed inflammatory
      changes with scattered CLL cells. The final histopathology demonstrated an 18-cm
      long and 4-cm wide giant fibrovascular polyp that was removed in 2 pieces. The
      polyp was composed of atypical adipose tissue with scattered giant cells and
      spindle-shaped cells as well as foci of CLL. Mouse double minute 2 homolog
      amplification was noted by fluorescence in situ hybridization diffusely in the
      giant polyp consistent with well-differentiated liposarcoma in a giant
      fibrovascular polyp. 

PMID- 24458179
TI  - The electromagnetic interference of mobile phones on the function of a gamma
      camera.
AB  - PURPOSE: The aim of the present study is to evaluate whether or not the
      electromagnetic field generated by mobile phones interferes with the function of
      a SPECT gamma-camera during data acquisition. METHODS: We tested the effects of 7
      models of mobile phones on 1 SPECT gamma-camera. The mobile phones were tested
      when making a call, in ringing mode, and in standby mode. The gamma-camera
      function was assessed during data acquisition from a planar source and a point
      source of Tc with activities of 10 mCi and 3 mCi, respectively. A significant
      visual decrease in count number was considered to be electromagnetic interference
      (EMI). RESULTS: The percentage of induced EMI with the gamma-camera per mobile
      phone was in the range of 0% to 100%. The incidence of EMI was mainly observed in
      the first seconds of ringing and then mitigated in the following frames.
      CONCLUSIONS: Mobile phones are portable sources of electromagnetic radiation, and
      there is interference potential with the function of SPECT gamma-cameras leading
      to adverse effects on the quality of the acquired images.

PMID- 24458180
TI  - Conjunctival MALT lymphoma: utility of FDG PET/CT for diagnosis, staging, and
      evaluation of treatment response.
AB  - A 67-year-old woman was referred for staging of a mucosa-associated lymphoid
      tumor lymphoma involving the left conjunctiva. CT scan had shown paravertebral
      and pelvic masses, and a breast nodule. FDG PET/CT demonstrated moderately
      increased uptake in the left ocular conjunctiva and confirmed the paravertebral
      and pelvic masses and the breast nodule. Moreover, abnormal FDG uptake was shown
      in 2 breast nodules, the flank, the gluteus maximus, and the gastric cardia. The
      patient received 6 cycles of rituximab-bendamustine chemotherapy with a complete
      clinical and metabolic response at the 6-month follow-up PET/CT and remained
      relapse-free without visual acuity problem after a 36-month follow-up. 

PMID- 24458181
TI  - Whole-body (99m)Tc-octreotide scintigraphy with SPECT/CT to detect occult tumor
      inducing paraneoplastic osteomalacia.
AB  - A 32-year-old woman presented with progressive myalgia, bone pain, fatigue,
      insufficiency hip fractures, high urine phosphate, and low serum phosphate and
      vitamin D levels. These findings were suggestive of oncogenic osteomalacia. A
      whole-body Tc-octreotide scintigraphy with SPECT/CT showed uptake on a sclerotic
      intramedullary lesion in the left medial tibia plateau. MRI depicted a solid
      lesion. The lesion was surgically removed; the patient became asymptomatic, and
      follow-up laboratory results normalized. Histopathologic examination revealed a
      vascular hemangiopericytoma-like tumor, positive for somatostatin receptor (SSR
      2). Whole-body Tc-octreotide scintigraphy with SPECT/CT may detect occult
      oncogenic osteomalacia tumors. 

PMID- 24458182
TI  - FDG-PET images of acrometastases.
AB  - Skeletal metastasis is common in patients with malignancy, but very few patients
      have acrometastasis, that is, metastasis to the hand or foot. We present 2 cases
      of acrometastasis from lung cancer where primary and metastatic foci were
      demonstrated on FDG-PET. The first case involves a 53-year-old man who complained
      of left foot pain and had osteolytic metastasis in the left calcaneus due to lung
      adenocarcinoma. True whole-body PET demonstrated lung cancer with calcaneal
      metastasis. Another case involves a 62-year-old man with large cell carcinoma of
      the right lung who complained of right wrist pain. Osteolytic metastasis of the
      hamate was demonstrated on images. 

PMID- 24458183
TI  - Diagnostic accuracy of (11)C-choline PET/CT in preoperative lymph node staging of
      bladder cancer: a systematic comparison with contrast-enhanced CT and histologic
      findings.
AB  - AIM: The aim of this study was to evaluate the role of C-choline PET/CT in the
      preoperative evaluation of the nodal involvement of patients with bladder
      carcinoma (BC) suitable for radical cystectomy and extended pelvic lymph node
      dissection in comparison with contrast-enhanced CT (CECT) using the pathologic
      specimen as reference standard. PATIENTS AND METHODS: Twenty-six consecutive
      patients (69.5 +/- 9.3 years; range, 49-84) with histologically proven
      transitional cell BC were treated with radical cystectomy and pelvic lymph node
      dissection and were enrolled from April 2011 to January 2013. In all patients,
      paravesical, internal, eternal, and common iliac nodes as well as obturatory,
      presacral, preaortic, and precaval lymph nodes (LNs) were dissected up to the
      origin of the inferior mesentery artery. The areas of the LN dissection were
      grouped as follow: region A included preaortic and precaval LNs; region B
      included paravesical, common, internal and external iliac, obturatory, and
      presacral LNs in the right pelvis; region C included paravesical, common,
      internal and external iliac, obturatory, and presacral LNs in the left pelvis. C
      choline PET/CT and abdominal CECT were used to assess the presence of lymph node
      metastases on a per patient, region, and lesion analysis using the results of
      surgical specimens obtained at operation as criterion standard. RESULTS: Seven of
      26 patients (26.9%) showed nodal metastases at pathologic analysis. Overall, 844
      LNs were evaluated, and 38 of them (4.5%) showed metastatic involvement. On a
      patient-based analysis, C-choline PET/CT showed a sensitivity of 42% and
      specificity of 84%, whereas, CECT showed a sensitivity of 14% and specificity of
      89%. On a region-based analysis, C-choline PET/CT showed a sensitivity of 11% and
      specificity of 82%, whereas CECT showed a sensitivity of 5% and specificity of
      80%. On a lesion (LN)-based analysis, C-choline PET/CT showed a sensitivity of
      10% and specificity of 64%, whereas CECT showed a sensitivity of 2% and
      specificity of 63%. CONCLUSIONS: C-choline PET/CT could provide additional
      diagnostic information in preoperative nodal staging of patients with invasive BC
      in comparison with CECT. A study with a larger population should determine if C
      choline PET/CT could be recommended as a routine technique in high-risk patients
      with BC.

PMID- 24458184
TI  - Colorectal carcinoma with bone metastases detected by 18F-choline PET/CT.
AB  - We report a case of metastatic colorectal carcinoma detected by F-choline PET/CT.
      A 72-year-old man with history of prostate cancer (previously treated with
      prostatectomy) underwent F-choline PET/CT for restaging. PET/CT revealed a focal
      area of increased F-choline uptake corresponding to a rectal nodule. Furthermore,
      2 areas of increased radiopharmaceutical uptake were evident in the right
      clavicle and in the body of the 10th dorsal vertebra, corresponding to the
      osteolytic lesions. Based on these PET/CT findings, the patient underwent biopsy
      of the rectal nodule and left clavicular lesion. Histologic examination
      demonstrated the presence of a colorectal carcinoma metastatic to the bone. 

PMID- 24458185
TI  - Radioembolization with 90Y resin microspheres for HCC patients with extensive
      tumor thrombosis into the extrahepatic vessels.
AB  - Tc-MAA uptake in the portal vein tumor thrombus may be a predictor of a favorable
      response to radioembolization. We report here 2 patients with hepatocellular
      carcinoma and massive intrahepatic and extrahepatic tumor thrombus that showed Tc
      MAA uptake in SPECT/CT, who underwent radioembolization with Y resin
      microspheres. The patients did not experience any adverse effects. 

PMID- 24458186
TI  - Multiple FDG-avid injection site granulomas due to lovenox injection.
AB  - An initial staging FDG PET/CT scan in a 15-year-old female patient with lymphoma
      revealed FDG-avid tumor in the mediastinum and the neck. After chemotherapy, a
      restaging PET/CT scan was performed. Although mediastinal and cervical lesions
      were not visualized, multiple new foci of activity were noted in the bilateral
      anterior thighs, which corresponded to soft tissue nodules in the subcutaneous
      tissue on the low-dose CT. On the third PET/CT study, multiple new foci appeared
      in the subcutaneous tissue in the anterior abdomen. Additional clinical history
      was obtained, indicating multiple recent subcutaneous injections of
      anticoagulants. 

PMID- 24458187
TI  - (11)C-acetate PET/CT in a case of recurrent hemangiopericytoma.
AB  - Intracranial hemangiopericytoma (IHPC) is a rare tumor representing less than 1%
      of all CNS tumors and is often indistinguishable from meningioma on structural
      imaging alone. Unlike meningioma, IHPC is an aggressive tumor with the propensity
      for early locoregional recurrence and distant metastases. Hence, its management
      strategies differ greatly from that of meningioma. Some investigators have
      reported the potential role of multitracers (F-FDG, C-methionine, and O-H2O) PET
      imaging in distinguishing IHPC from meningioma. We described the findings of dual
      tracer (C-acetate and F-FDG) PET/CT imaging in a histopathologically proven case
      of IHPC with extensive extracranial osseous metastases that showed significantly
      greater C-acetate avidity. 

PMID- 24458188
TI  - The isotopic effects of deuteration on optoelectronic properties of conducting
      polymers.
AB  - The attractive optoelectronic properties of conducting polymers depend
      sensitively upon intra- and inter-polymer chain interactions, and therefore new
      methods to manipulate these interactions are continually being pursued. Here, we
      report a study of the isotopic effects of deuterium substitution on the
      structure, morphology and optoelectronic properties of regioregular poly(3
      hexylthiophene)s with an approach that combines the synthesis of deuterated
      materials, optoelectronic properties measurements, theoretical simulation and
      neutron scattering. Selective substitutions of deuterium on the backbone or side
      chains of poly(3-hexylthiophene)s result in distinct optoelectronic responses in
      poly(3-hexylthiophene)/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM)
      photovoltaics. Specifically, the weak non-covalent intermolecular interactions
      induced by the main-chain deuteration are shown to change the film crystallinity
      and morphology of the active layer, consequently reducing the short-circuit
      current. However, side-chain deuteration does not significantly modify the film
      morphology but causes a decreased electronic coupling, the formation of a charge
      transfer state, and increased electron-phonon coupling, leading to a remarkable
      reduction in the open circuit voltage. 

PMID- 24458189
TI  - Nitrite reduction in leaves; Studies on isolated chloroplasts.
AB  - Chloroplast preparations from spinach leaves containing a high percentage of
      intact chloroplasts were capable of light dependent nitrite reduction at rates
      around 9 MUmol/mg chlorophyll/h for at least 50 min. This reduction was inhibited
      by DCMU but unaffected by uncouplers of photosynthetic phosphorylation. Nitrite
      reduction was not accompanied by a stoichiometric evolution of oxygen evolution.
      The disappearance of nitrite was accompanied by an approximately stoichiometric
      formation of reduced nitrogen. 

PMID- 24458190
TI  - The influence of inorganic nitrogen supply on carbohydrate and related metabolism
      in the blue-green alga, Anabaena cylindrica Lemm.
AB  - Enzymes representative of, and related to, the pentose phosphate pathway,
      glycolysis, and the tricarboxylic acid cycle have been demonstrated in
      supernatant and lamellar fractions of Anabaena cylindrica cultured in the
      presence of atmospheric nitrogen, ammonia, nitrite, and nitrate. Nitrogen-fixing
      and ammonia-assimilating algae contained essentially similar levels of most
      enzymes tested, with the notable exception of glyceraldehyde-3-phosphate
      dehydrogenase which showed increased NADPH-linked activity with concomitant
      diminution of NADH-linked activity when ammonia was supplied. The provision of
      nitrite or nitrate caused significant enhancements of glucose-6-phosphate
      dehydrogenase, 6-phosphogluconate dehydrogenase, and the related hexokinase and
      phosphohexoisomerase. Reduced activities of pyruvate kinase, malate
      dehydrogenase, phosphoenolpyruvate carboxylase, and both NADH and NADPH
      oxidoreductases were recorded for nitrate-grown alga.The stimulation of the
      pentose phosphate pathway, at the partial expense of glycolysis and the
      tricarboxylic acid cycle, in algae cultured with nitrite and nitrate was
      interpreted to be due to additional NADPH requirements imposed by induced nitrite
      reductase. Modification of the pyridine nucleotide linkage of glyceraldehyde-3
      phosphate dehydrogenase and the oxidoreductases was attributed to diversion of
      reductant to nitrite and nitrate reductases and nitrogenase. The results are
      considered to indicate regulation of blue-green algal metabolism determined by
      the availability of pyridine nucleotides. 

PMID- 24458191
TI  - Nitrate, nitrite and ammonia assimilation by leaves: Effect of light, carbon
      dioxide and oxygen.
AB  - The assimilation of nitrate, nitrite and ammonia in barley, wheat, corn and bean
      leaves was studied using (15)N-labelled molecules and either leaf chamber
      experiments with the uptake of the nitrogen species in the transpiration stream,
      or vacuum-infiltration experiments. The assimilation of (15)NO3 (-) into amino
      nitrogen was strictly dependent on light and ceased abruptly when the light was
      extinguished. If the leaves were exposed to air, CO2-free air or N2 there was no
      effect on the rate of NO3 (-) assimilation over 0.5 h. After 1.25 h of CO2-free
      air, NO3 (-) assimilation into amino acids was sharply reduced. Resupply of air
      at this time stimulated NO3 (-) assimilation and restored it to the rate observed
      in leaves exposed to air only. There was no recovery by tissue pretreated for
      1.25 h in N2 and subsequently resupplied with air. Incorporation of (15)NO2 (-)
      was also markedly dependent on light with little reduction occurring in the dark.
      Incorporation of (15)NH4 (+) into amino acids was stimulated 5 fold by light but
      considerable incorporation occurred in the dark. The presence of 100 mM NO3 (-)
      had no effect on the rate of incorporation of (15)NO2 (-) or (15)NH4 (+). Nitrite
      at 1 mM had no effect on (15)NO3 (-) incorporation but at 10 mM inhibited it
      completely after 0.5 h. Ammonia at 1 mM had no effect on (15)NO3 (-) or (15)NO2 (
      ) incorporation and while 10 mM inhibited incorporation for 0.5 h this inhibition
      did not persist. 

PMID- 24458192
TI  - Differential hormone responses in different growing zones of the bean hypocotyl.
AB  - Differential growth responses to plant growth substances-a cytokinin (benzyl
      adenine), gibberellic acid (GA3), indoleacetic acid (IAA), abscisic acid (ABA),
      coumarin and ethylene-and to environmental factors (carbon dioxide and red light)
      were found in tissues of different age in a 4-cm segment of the etiolated
      hypocotyl of Phaseolus vulgaris L. Elongation in all zones of the hypocotyl which
      were growing or were about to grow was generally enhanced, but each factor or
      phytohormone acted specifically on a particular zone, in the order cytokinin, red
      light, GA3, CO2, C2H4 and IAA, going from the top of the hypocotyl. ABA inhibited
      elongation both in the red-light- and GA3-dependent, immature zones and in the
      IAA-dependent, relatively mature zones. The effects of C2H4 and CO2 were opposite
      and those of auxin and coumarin were similar. 

PMID- 24458193
TI  - Anatomical and ultrastructural changes in aleurone and myrosin cells of Sinapis
      alba during germination.
AB  - The cells of the embryo of Sinapis alba L. include either aleurone or myrosin
      grains and all cells contain oil bodies. Aleurone grains and oil bodies are
      degraded during germination. The myrosin grains of each myrosin cell, on the
      other hand, gradually turn into one big vacuole containing the myrosin. Probably
      very little, if any, new myrosin is formed in the cotyledons and hypocotyl of the
      seedling after germination. No difference was found between aleurone and myrosin
      cells in the development of organelles. The cells of provascular bundles of the
      mature embryo contain different amounts of aleurone grains in different stages of
      development, and their organelles are more developed than those of all other
      cells. 

PMID- 24458194
TI  - Temperature dependence of phytochrome dark reactions.
AB  - The dark reversion and the destruction reaction of the phytochrome of squash
      (Cucurbita pepo L.) cotyledons show different temperature behaviour in the
      temperature range 15-35 degrees . The Arrhenius activation energy of the
      destruction reaction is temperature independent whereas that of the reversion
      reaction shows a jump at 20 degrees . This indicates an interaction of
      phytochrome molecules with membranes. A reaction scheme is discussed which can
      explain the differences of the dark kinetics in a quantitative manner. 

PMID- 24458195
TI  - Dependence of phytochrome dark reactions on the initial photostationary state.
AB  - Under conditions of continuous irradiation, the P jr destruction rate constants
      (k d ) of phytochrome in hooks and cotyledons of squash (Cucurbita pepo L.)
      seedlings do not depend on the photostationary state philambda and are the same
      in both organs. On the other hand, the rate constants of the dark reversion and
      the first destruction step, plotted as a function of phi lambda (0) , show
      optimum curves with maxima between phi lambda (0) and 0.5. Similar results were
      obtained for dark reactions of mustard (Sinapis alba L.)-hook phytochrome in
      vivo. This indicates a cooperative behaviour of these phytochrome dark reactions.

PMID- 24458196
TI  - [Rapidly labelled low molecular weight components in nucleic acid preparations
      from plant cells].
AB  - After pulse-labelling with [(3)H]nucleosides and [(3)H]orotic acid of freely
      suspended callus cells of Petroselinum sativum and tissue fragments of the
      liverwort Riella helicophylla, rapidly labelled low molecular weight components
      were detected among the total nucleic acids when these were extracted in the
      presence of Mg(2+) and finally precipitated with alcohol. These highly labelled
      species could clearly be distinguished from the 5 S- and 4 S-RNA on the basis of
      their migration in agarose-polyacrylamide gels (2.4%) and their elution from
      Sephadex G-150 columns. No degradation was obtained with DNase and RNase. By
      using [(14)C]ATP as a marker it was found that the low molecular components
      consisted mainly of nucleoside triphosphates. Only small amounts of nucleoside
      diphosphates were detected, which were obviously formed by degradation of the
      former. Nucleic acid preparations free of nucleoside phosphates were obtained by
      using Mg-free extraction buffers containing EDTA. 

PMID- 24458197
TI  - Early detection of lung cancer: a statement from an expert panel of the Swiss
      university hospitals on lung cancer screening.
AB  - The discussion about setting up a program for lung cancer screening was launched
      with the publication of the results of the National Lung Screening Trial, which
      suggested reduced mortality in high-risk subjects undergoing CT screening.
      However, important questions about the benefit-harm balance and the details of a
      screening program and its cost-effectiveness remain unanswered. A panel of
      specialists in chest radiology, respiratory medicine, epidemiology, and thoracic
      surgery representing all Swiss university hospitals prepared this joint statement
      following several meetings. The panel argues that premature and uncontrolled
      introduction of a lung cancer screening program may cause substantial harm that
      may remain undetected without rigorous quality control. This position paper
      focuses on the requirements of running such a program with the objective of
      harmonizing efforts across the involved specialties and institutions and defining
      quality standards. The underlying statement includes information on current
      evidence for a reduction in mortality with lung cancer screening and the
      potential epidemiologic implications of such a program in Switzerland.
      Furthermore, requirements for lung cancer screening centers are defined, and
      recommendations for both the CT technique and the algorithm for lung nodule
      assessment are provided. In addition, related issues such as patient management,
      registry, and funding are addressed. Based on the current state of the knowledge,
      the panel concludes that lung cancer screening in Switzerland should be
      undertaken exclusively within a national observational study in order to provide
      answers to several critical questions before considering broad population-based
      screening for lung cancer.

PMID- 24458198
TI  - Observing and quantifying fibroblast-mediated fibrin gel compaction.
AB  - Cells embedded in collagen and fibrin gels attach and exert traction forces on
      the fibers of the gel. These forces can lead to local and global reorganization
      and realignment of the gel microstructure. This process proceeds in a complex
      manner that is dependent in part on the interplay between the location of the
      cells, the geometry of the gel, and the mechanical constraints on the gel. To
      better understand how these variables produce global fiber alignment patterns, we
      use time-lapse differential interference contrast (DIC) microscopy coupled with
      an environmentally controlled bioreactor to observe the compaction process
      between geometrically spaced explants (clusters of fibroblasts). The images are
      then analyzed with a custom image processing algorithm to obtain maps of the
      strain. The information obtained from this technique can be used to probe the
      mechanobiology of various cell-matrix interactions, which has important
      implications for understanding processes in wound healing, disease development,
      and tissue engineering applications. 

PMID- 24458199
TI  - Bone turnover markers and pharmacokinetics of a new sustained-release formulation
      of the cathepsin K inhibitor, ONO-5334, in healthy post-menopausal women.
AB  - A sustained-release tablet (SRT) of ONO-5334 was compared to the immediate
      release tablet (IRT) dose, which demonstrated effects on bone mineral density
      (BMD) comparable to those of therapy with alendronate. The single-dose phase was
      a randomized, partial single-blind, crossover study where 50-, 100-, and 300-mg
      SRTs and 300-mg IRTs were administered to nine post-menopausal women. The
      multiple-dose phase was a randomized, double-blind, placebo-controlled, parallel
      group study where 100- and 300-mg SRTs, or placebo were administered to 24 women.
      After a single administration of a 300-mg SRT, mean C max was 3.3-fold lower,
      mean AUCinf was 0.83-fold lower and mean C 24h was 5.4-fold higher compared to
      the 300-mg IRT. Repeated SRT dosing did not significantly affect PK, although C
      24h increased slightly. After a single ONO-5334 dose, serum CTX-I was suppressed
      by ~50 % within 1 h, reaching maximum suppression 6 h post-dose. Greater
      suppression was maintained longer by the 300-mg SRT vs. the 300-mg IRT. Second
      morning void and cumulative urine CTX-I showed clear dose-response effects
      at/over 24 h for SRT, with maximum suppression occurring at/over 24 h (except 50-
      and 300-mg cumulative urine). Repeated dosing suggested greater suppression of
      urine CTX-I. Compared with the IRT, the SRT showed reduced C max, greater C 24h,
      and slightly reduced AUCinf dose for dose. The SRT showed clear dose-response
      suppression on bone resorption and greater efficacy dose for dose vs. the IRT. 

PMID- 24458200
TI  - Chronic muscle stimulation improves insulin sensitivity while increasing
      subcellular lipid droplets and reducing selected diacylglycerol and ceramide
      species in obese Zucker rats.
AB  - AIMS/HYPOTHESIS: Although insulin resistance has been associated with
      accumulations of specific intramuscular fatty acids and altered subcellular
      localisation of lipid droplets, these concepts remain controversial. Therefore,
      we aimed to identify specific intramuscular fatty acids and subcellular lipid
      localisations associated with improved insulin sensitivity following chronic
      muscle contraction. METHODS: In lean and insulin-resistant obese Zucker rats the
      tibialis anterior muscle was stimulated (6 h/day for 6 days). Thereafter, muscles
      were examined for insulin sensitivity, intramuscular lipid droplet localisation
      and triacylglycerol (TAG), diacylglycerol (DAG) and ceramide fatty acid
      composition. RESULTS: In lean and obese animals, regardless of muscle type,
      chronic muscle contraction improved muscle insulin sensitivity and increased
      intramuscular levels of total and most C14-C22 TAG fatty acids (p < 0.05).
      Therefore, accumulation in subcellular lipid droplet compartments reflected the
      oversupply of lipids within muscle. In contrast, improvements in insulin
      sensitivity induced by muscle contraction were associated with reductions in
      specific DAG and ceramide species that were not uniform in red and white muscle
      of obese rats. However, these reductions were insufficient to fully normalise
      insulin sensitivity, indicating that other mechanisms are involved.
      CONCLUSIONS/INTERPRETATION: Reductions in 18 C length DAG and ceramide species
      were the most consistent in red and white muscle and therefore may represent
      therapeutic targets for improving insulin sensitivity.

PMID- 24458202
TI  - Coat's-like exudation in rhodopsin retinitis pigmentosa: successful treatment
      with an intravitreal dexamethasone implant.
AB  - PURPOSE: Role of intravitreal injection of dexamethasone implant (Ozurdex) for
      refractory macular thickening. METHODS: A case report of a 13-year-old boy with
      Rhodopsin-positive, CRB1-negative retinitis pigmentosa presenting with Coat's
      like exudative vitreoretinopathy and treatment-resistant cystoid macular oedema.
      RESULTS: A reduction in the macular thickening following a single injection of
      Ozurdex. CONCLUSION: We present our experience in successful treatment of
      refractory macular oedema with intravitreal injection of dexamethasone implant
      resulting in clinically significant resolution of macular thickening.

PMID- 24458201
TI  - Association between cystoid spaces on indocyanine green hyperfluorescence and
      optical coherence tomography after vitrectomy for diabetic macular oedema.
AB  - PURPOSE: To study retrospectively the characteristics of residual indocyanine
      green (ICG) fluorescence after ICG-assisted vitrectomy and the association with
      spectral-domain optical coherence tomography (SD-OCT) findings in diabetic
      macular oedema (DMO). METHODS: Thirteen consecutive eyes of 12 patients for whom
      fundus near-infrared fluorescence and 20 degrees  retinal sectional images were
      obtained using HRA2 and Spectralis OCT, respectively, 5 days after vitrectomy
      combined with ICG-assisted inner limiting membrane peeling for DMO. The
      relationship between the characteristics of the ICG hyperfluorescence and the
      cystoid spaces in the outer plexiform layer (OPL) on SD-OCT images was evaluated.
      RESULTS: A total of 390 well-demarcated areas of ICG hyperfluorescence were
      delineated on 20 degrees  radial OCT scans dissecting the fovea 5 days after
      vitrectomy. The areas of ICG hyperfluorescence in the parafovea or perifovea were
      significantly smaller than those at the fovea. Most areas of hyperfluorescence
      were irregularly shaped in the parafovea and perifovea, whereas 18 of 38 areas of
      hyperfluorescence were round or oval at the fovea (P<0.001). SD-OCT delineated
      the cystoid spaces in the OPL in 73 areas of hyperfluorescence that were round or
      oval and accompanied by dark spots more frequently than that without cystoid
      spaces on OCT images (P<0.001 and P=0.002). Of the 123 cystoid spaces in the OPL
      on OCT images, 44 did not have ICG hyperfluorescence, had lower OCT reflectivity,
      and contained fewer hyperreflective foci than those with ICG hyperfluorescence
      (P<0.001 and P=0.020). CONCLUSION: The results provided novel interpretations of
      the ICG hyperfluorescence and its association with OCT characteristics of the
      cystoid spaces in DMO.

PMID- 24458203
TI  - Predictors for the progression of geographic atrophy in patients with age-related
      macular degeneration: fundus autofluorescence study with modified fundus camera.
AB  - PURPOSE: We examined the association between abnormal fundus autofluorescence
      (FAF) features on images obtained by a modified fundus camera (mFC) and
      geographic atrophy (GA) progression in patients with age-related macular
      degeneration (AMD). METHODS: Serial FAF images of 131 eyes from 131 patients with
      GA were included in the study. All FAF images were obtained with an mFC
      (excitation, ~ 500-610 nm; emission, ~ 675-715 nm). The GA area was quantified at
      baseline and 1 year later using a customized segmentation program. The yearly GA
      enlargement rate was then calculated. Abnormal FAF patterns in the junctional
      zone of GA were classified as None or Minimal change, Focal, Patchy, Banded, or
      Diffuse according to previously published classification based on confocal
      scanning laser ophthalmoscopy (cSLO). The relationship between GA enlargement and
      abnormal FAF was evaluated. RESULTS: The mean rate of GA enlargement was the
      fastest in eyes with Diffuse pattern (1.74 mm(2) per year), followed by eyes with
      the Banded pattern (1.69 mm(2) per year). Binary logistic regression analysis
      revealed that eyes with the Banded and Diffuse pattern had significantly higher
      risk for GA enlargement compared with eyes with the other patterns. CONCLUSIONS:
      FAF image obtained by mFC appears to be acceptable for evaluating GA in
      accordance with an established cSLO-based classification. Eyes with the Banded or
      the Diffuse patterns of abnormal FAF at baseline indicate a high risk for GA
      progression. Identifying patients at high risk for GA progression using an mFC is
      broadly available method that can provide additional information to help predict
      disease course.

PMID- 24458204
TI  - [One year later: has there been "MEDLINE effect" in Archivos?].

PMID- 24458205
TI  - [Health and safety professional roles and competencies to promote company-level
      integration of preventive actions. A Delphy study].
AB  - OBJECTIVE: To describe the view of faculty who train health and safety
      professionals on the roles and competencies needed to promote the integration of
      preventive actions at the company level. METHODS: We used a Delphi method, in
      three rounds, on an intentional sample of experts, and asked them to rate the
      appropriateness, relevance and acceptability of 8 professional roles, on a scale
      of 1 to 9 points. We also asked them to formulate and rank order the
      corresponding competencies, in order of importance. RESULTS: Participant
      responses (n=76, 58% of the initially identified faculty) show a broad consensus
      when assessing professional roles (over 85% of participants rated two of these
      roles highly, with scores between 7 and 9) and general agreement on the three
      most important competencies in terms of knowledge, skills and attitudes to
      promote the integration of preventive actions. CONCLUSIONS: The experts
      participating in this study agreed that the main roles to be performed by health
      and safety professionals to promote prevention integration are as advisors and
      trainers. The competencies considered most important are knowledge about the
      company activity, its risks and the problems linked to the activity (to know),
      ability to work in multidisciplinary teams (to know how), and to perform
      professional duties ethically, with independence and impartiality (to know how to
      be).

PMID- 24458206
TI  - [Identification of occupational diseases in a tertiary care hospital].
AB  - OBJECTIVES: Official recognition of occupational diseases (OD) in Spain is very
      poor. In 2010, the Occupational Disease Unit (ODU) of Parc de Salut Mar (PSMAR)
      was created to identify and report the suspect of OD among hospital patients. The
      aim of the study is to analyze the activity of the Occupational Disease Unit
      between 2010 and 2012. METHODS: Patients evaluated by the Occupational Disease
      Unit were identified through referrals from clinical services and retrospective
      reviews of selected pathologies from the hospital discharge register in the
      period 2010-2012. Cases are evaluated systematically, using an evidence-based
      approach to assess the relationship between occupational exposures and disease.
      We analyze the frequency of cases together with the positive predictive value
      (PPV) and corresponding 95% confidence intervals (95%CI) for the confirmation
      procedure as suspected cases of OD according to the case origin, diagnostic
      group, age and sex. RESULTS: From a total of 140 patients with suspected OD
      identified by the Occupational Disease Unit, 47% were located through
      retrospective reviews of the hospital discharge registries (n=66) and the
      remainder from clinical services referrals (n=74). Among these cases 54% were
      cancers, 21% hearing losses, 16% musculoskeletal disorders, 6% dermatological
      diseases, 2% respiratory tract diseases and 1% neurological diseases. The
      Occupational Disease Unit confirmed suspected OD in 34 cases. The PPV for cases
      referred from clinical services was 39% (95% CI = 27.39-50.99) and 7.6% (95% CI =
      0.43-14.72) for the discharge register retrospective review. CONCLUSION:
      Hospitals can contribute to the identification of OD, and referral of suspected
      OD by clinical services to a specialized occupational medicine unit is
      recommended as the most appropriate strategy.

PMID- 24458207
TI  - [Evaluation of a novel flu vaccination campaign among health personnel for the
      2011-2012 season].
AB  - The objective was to evaluate the healthcare personnel seasonal influenza
      immunization program in the 2011-2012 flu season. The campaign included several
      innovative actions (informational brochure, recommendations for unvaccinated
      staff to wear a mask, acknowledgement letters, etc). Coverage and characteristics
      of the health personnel were compared with the previous season using the chi
      square test. Vaccination coverage for the 2011-12 flu season was 26.5%, compared
      to 24.5% achieved in 2010-2011 (p=0.052). The improvement in vaccination coverage
      approached statistical significance but remains very low. To improve these low
      vaccination levels, we recommend developing other strategies, such as incentive
      policies or making vaccination mandatory. 

PMID- 24458208
TI  - [The European Commission hides behind experts with conflicts of interest to
      delay, again, the regulation of endocrine disruptors].

PMID- 24458209
TI  - [Screening in occupational medicine: prevention and research].

PMID- 24458210
TI  - Single-stage repair of paralytic ectropion using a novel modification of the
      tarsoconjunctival flap.

PMID- 24458211
TI  - Clinical impact of predicting CCND1 amplification using plasma DNA in superficial
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: This study was designed to evaluate the clinical benefit of
      predicting the cyclin D1 (CCND1) status using cell-free plasma DNA in superficial
      esophageal squamous cell carcinoma (ESCC) patients. METHODS: The ratio of the
      CCND1 (11q13) dosage to the DRD2 (11q22-23) dosage (C/D ratio) as the CCND1 copy
      number was evaluated. This study was divided into three steps: (1) demonstration
      of the feasibility, (2) evaluation of whether the plasma C/D ratio assay could
      monitor tumor dynamics, and (3) a validation study in 63 consecutive superficial
      ESCC (pTis-T1) patients and 40 healthy volunteers. RESULTS: (1) The plasma C/D
      ratio was significantly higher (p = 0.0369) in superficial ESCC patients than in
      the controls in a preliminary test. (2) The high plasma C/D ratio appeared to
      reflect the tumor levels of the CCND1 status and was reduced in postoperative
      plasma samples (p = 0.1154) and samples following endoscopic resection (p =
      0.0845). (3) Validation analysis revealed that the plasma C/D ratio was
      significantly higher in superficial ESCC patients than in controls (p < 0.0001).
      The frequency of recurrence was significantly higher (p = 0.0198), and recurrence
      free survival was significantly shorter (p = 0.0075) in patients with a high
      plasma C/D ratio. Moreover, a high C/D ratio was shown to be an independent risk
      factor for recurrence on multivariate analysis [p = 0.0334; odds ratio 10.58
      (range 1.203-93.23)]. CONCLUSION: The prediction of CCND1 amplification by plasma
      DNA may be a new complementary clinical biomarker for recurrence in patients with
      superficial ESCC.

PMID- 24458212
TI  - Protein supplements: do they alter dietary intakes?
AB  - Effects of protein versus mixed macronutrient supplementation on total energy
      intake (TEI) and protein intake during an ad libitum diet were examined. Trained
      males undertook two, 2-week dietary interventions which were randomized, double
      blinded, and separated by 2 weeks. These were high-protein supplementation (HP:
      1034.5 kJ energy, 29.6 g protein, 8.7 g fat and 12.3 g CHO) and standard meal
      supplementation (SM: 1039 kJ energy, 9.9 g protein, 9.5 g fat, and 29.4 g CHO)
      consumed daily following a week of baseline measures. Eighteen participants
      finished both interventions and one only completed HP. TEI (mean +/- SD) was not
      different between baseline (11148 +/- 3347 kJ) and HP (10705 +/- 3143 kJ) nor
      between baseline and SM (12381 +/- 3877 kJ), however, TEI was greater with SM
      than HP (923 +/- 4015 kJ p = .043). Protein intake (%TEI) was greater with HP
      (22.4 +/- 6.2%) than baseline (19.4 +/- 5.4%; p = .008) but not SM (20.0 +/-
      5.0%). No differences in absolute daily protein intake were found. Absolute CHO
      intake was greater with SM than HP (52.0 +/- 89.5 g, p = .006). No differences in
      fat intake were found. Body mass did not change between baseline (82.7 +/- 11.2
      kg) and either HP (83.1 +/- 11.7 kg) or SM (82.9 +/- 11.0 kg). Protein
      supplementation increases the relative proportion of protein in the diet, but
      doesn't increase the absolute amount of total protein or energy consumed. Thus
      some compensation by a reduction in other foods occurs. This is in contrast to a
      mixed nutrient supplement, which does not alter the proportion of protein
      consumed but does increase TEI.

PMID- 24458213
TI  - Diastereomeric ratio determination by high sensitivity band-selective pure shift
      NMR spectroscopy.
AB  - An NMR method is reported that allows diastereomeric ratios to be determined even
      in crowded spectra or where chemical shift differences are small compared to
      multiplet widths. Band-selective pure shift NMR collapses multiplets to singlets,
      greatly improving spectral resolution while largely retaining, or even enhancing,
      signal-to-noise ratio. 

PMID- 24458214
TI  - Retrieving autobiographical memories influences judgments about others: the role
      of metacognitive experiences.
AB  - This research investigates whether metacognitive experiences accompanying the
      retrieval of autobiographical memories influence judgments about others. Based on
      social projection research, we tested the hypothesis that ease-of-retrieval,
      affecting how the self is perceived, affects first impressions. In line with this
      prediction, Experiment 1 showed that participants asked to recall a few personal
      instances of assertive behavior (easy retrieval) judged an unknown person to be
      more assertive than participants recalling many instances (difficult retrieval).
      Experiment 2, targeting creativity, provided evidence for the retrieval-ease
      mechanism: The effect disappeared when ease-of-retrieval was discredited as
      informational source in a misattribution paradigm. Finally, Experiments 3 and 4
      replicated this pattern for the same personality traits and demonstrated two
      boundary conditions: Participants' ease of autobiographical recalls affected
      judgments of in- but not outgroup members (Experiment 3), and judgments of
      unknown others were affected after autobiographical recall but not after
      recalling behaviors of someone else (Experiment 4). 

PMID- 24458215
TI  - Video games do affect social outcomes: a meta-analytic review of the effects of
      violent and prosocial video game play.
AB  - Whether video game play affects social behavior is a topic of debate. Many argue
      that aggression and helping are affected by video game play, whereas this stance
      is disputed by others. The present research provides a meta-analytical test of
      the idea that depending on their content, video games do affect social outcomes.
      Data from 98 independent studies with 36,965 participants revealed that for both
      violent video games and prosocial video games, there was a significant
      association with social outcomes. Whereas violent video games increase aggression
      and aggression-related variables and decrease prosocial outcomes, prosocial video
      games have the opposite effects. These effects were reliable across experimental,
      correlational, and longitudinal studies, indicating that video game exposure
      causally affects social outcomes and that there are both short- and long-term
      effects. 

PMID- 24458216
TI  - Motivation to control prejudice predicts categorization of multiracials.
AB  - Multiracial individuals often do not easily fit into existing racial categories.
      Perceivers may adopt a novel racial category to categorize multiracial targets,
      but their willingness to do so may depend on their motivations. We investigated
      whether perceivers' levels of internal motivation to control prejudice (IMS) and
      external motivation to control prejudice (EMS) predicted their likelihood of
      categorizing Black-White multiracial faces as Multiracial. Across four studies,
      IMS positively predicted perceivers' categorizations of multiracial faces as
      Multiracial. The association between IMS and Multiracial categorizations was
      strongest when faces were most racially ambiguous. Explicit prejudice, implicit
      prejudice, and interracial contact were ruled out as explanations for the
      relationship between IMS and Multiracial categorizations. EMS may be negatively
      associated with the use of the Multiracial category. Therefore, perceivers'
      motivations to control prejudice have important implications for racial
      categorization processes. 

PMID- 24458217
TI  - New NASPGHAN research agenda to target the public.

PMID- 24458218
TI  - Association of INSIG2 rs9308762 with ALT level independent of BMI.
AB  - OBJECTIVES: An increasing number of people are at risk for developing
      nonalcoholic fatty liver disease (NAFLD). Because obesity is a risk factor for
      NAFLD, the common variants of obesity-susceptible genes may be associated with
      NAFLD. Our aim was to identify whether the obesity-susceptible gene variants
      (rs9939609, rs9930506, and rs4783819 in fat mass and obesity-associated gene
      (FTO); rs12970134 and rs17782313 in melanocortin-4 receptor gene (MC4R); and
      rs7566605, rs13428113, and rs9308762 in insulin-induced gene 2 [INSIG2]) were
      associated with NAFLD. METHODS: The case-control study recruited 1027 Chinese
      children ages 7 to 18 years, including 162 children with NAFLD and 865 children
      without NAFLD. Anthropometric measurements, alanine transaminase (ALT) detection,
      liver ultrasound examination, and genotyping of 8 gene variants were performed.
      RESULTS: The A-allele of FTO rs9939609 was associated with increased NAFLD risk
      (P = 0.029, odds ratio  1.43), but was not significant after being adjusted for
      body mass index (BMI) (P = 0.268). We also found an association between the 2
      variants (rs12970134 in MC4R and rs9308762 in INSIG2) and ALT level. For
      rs12970134, each additional A-allele increased ALT level by 1.87 IU/L (P =
      0.032). For rs9308762, the homozygotes of the C-allele had a higher ALT level
      than the T-allele carriers (beta = 3.19, P = 0.007). After adjustment for BMI,
      the former association did not exist, whereas the latter reminded significant (P
      = 0.003). CONCLUSIONS: The FTO rs9939609 A-allele increased risk of NAFLD and
      MC4R rs12970134 was associated with ALT level through an effect on BMI. The
      association between INSIG2 rs9308762 and ALT level was independent of BMI. The
      results provided evidence for identifying genetic factors of NAFLD and may be
      useful for risk assessment and personalized medicine of NAFLD.

PMID- 24458219
TI  - Effect of molecular adsorbents recirculating system treatment in children with
      acute liver failure caused by Wilson disease.
AB  - OBJECTIVES: Because fulminant Wilson disease (WD) has an extremely poor
      prognosis, the use of liver support that can bridge patients to liver
      transplantation is lifesaving. We report the experience of albumin dialysis in
      acute liver failure (ALF) caused by WD in children. METHODS: Chart review of
      children admitted for ALF secondary to acute WD and treated by the molecular
      adsorbents and recirculating system. Measures of copper level in blood and within
      the circuit during molecular adsorbents recirculating system (MARS) sessions were
      performed. Clinical and biological assessments after MARS session were reported.
      RESULTS: Four children, with a median age of 12.3 years, were treated from 2004
      to 2009 for a severe ALF associated with acute renal failure, haemolysis, and
      severe cholestasis. All of the children had a new Wilson index >12. A total of 14
      MARS sessions were performed, for a median duration of 7.5 hours. Tolerance was
      good, except for 1 child who experienced haemorrhage because of vascular injury
      following insertion of the dialysis catheter. A neurological improvement or
      stabilisation was noted in all of the children along with an improvement in the
      Fisher index and ammonia level after MARS treatment. MARS was able to remove
      copper, to decrease the serum copper level of 28% in mean, and to decrease the
      bilirubin and creatinin levels >25%. All of the children were subsequently
      underwent liver transplants with a good outcome without disability. CONCLUSIONS:
      MARS is able to remove copper and to stabilise children with ALF secondary to WD,
      allowing bridging to LT.

PMID- 24458221
TI  - UGT1A1*28 polymorphism in chronic lymphocytic leukemia: the first investigation
      of the polymorphism in disease susceptibility and its specific cytogenetic
      abnormalities.
AB  - Chronic lymphocytic leukemia (CLL) has been recently attributed to a combination
      of genetic predisposition and exposure to environmental factors. UDP
      glucuronosyltransferase (UGT)1A1*28 is an inborn polymorphism that results in
      significant downregulation of uridine diphosphate glucuronyltransferase 1-1
      (UGT1A1) activity, one of the most critical metabolizing enzymes involved in the
      detoxification of toxic substances, some of which contribute to CLL pathogenesis.
      Here, for the first time, we investigated the putative impact of UGT1A1*28 on CLL
      incidence and on the formation of the most common chromosomal abnormalities of
      CLL. UGT1A1*28 was investigated in 109 CLL patients and 108 healthy controls, and
      was associated with karyotypic and fluorescence in situ hybridization (FISH)
      results. A significant high frequency of the mutant genotype was observed in
      patients carrying abnormal FISH patterns, especially del(11q) and +12, which are
      CLL-specific abnormalities. We also observed a significant association between
      UGT1A1*28 and the intermediate to unfavorable cytogenetic CLL risk groups. No
      difference, though, was observed in genotypes between patients and controls.
      Therefore, we could suggest that UGT-deficient individuals may be at a greater
      risk for developing CLL-specific abnormalities. Our study might serve as a
      starting point to consider UGT1A1*28 polymorphism as one of the possible
      predisposing factors of CLL pathogenesis.

PMID- 24458222
TI  - A European community pharmacy-based survey to investigate patterns of
      prescription fraud through identification of falsified prescriptions.
AB  - AIM: To identify prescription drugs involved in falsified prescriptions in
      community pharmacies in 6 European countries. METHODS: A cross-sectional survey
      among 2,105 community pharmacies in Belgium, France, Italy, the Netherlands,
      Spain and Sweden was carried out to collect all suspect prescription forms. For
      each reported drug, the number of reported falsified prescriptions per thousand
      inhabitants was estimated. A falsification ratio was calculated by dividing the
      number of reports by the number of defined daily doses per 1,000 inhabitants per
      day for this drug, computed from national sale or reimbursement data. RESULTS: On
      862 prescription forms, benzodiazepines (zolpidem, bromazepam, alprazolam),
      buprenorphine (as an opioid maintenance drug) and tramadol were the most
      frequently reported. Depending on their level of use in each country,
      methylphenidate, morphine and flunitrazepam presented the highest falsification
      ratios, particularly in Spain, Belgium and France. CONCLUSIONS: Stimulants,
      opioids and some benzodiazepines were the most frequently reported drugs in this
      survey on falsified prescriptions, but differences between countries were
      observed.

PMID- 24458224
TI  - Case study: Muscle atrophy and hypertrophy in a premier league soccer player
      during rehabilitation from ACL injury.
AB  - The onset of injury and subsequent period of immobilization and disuse present
      major challenges to maintenance of skeletal muscle mass and function. Although
      the characteristics of immobilization-induced muscle atrophy are well documented
      in laboratory studies, comparable data from elite athletes in free-living
      conditions are not readily available. We present a 6-month case-study account
      from a professional soccer player of the English Premier League characterizing
      rates of muscle atrophy and hypertrophy (as assessed by DXA) during
      immobilization and rehabilitation after ACL injury. During 8 weeks of inactivity
      and immobilization, where the athlete adhered to a low carbohydrate-high protein
      diet, total body mass decreased by 5 kg attributable to 5.8 kg loss and 0.8 kg
      gain in lean and fat mass, respectively. Changes in whole-body lean mass was
      attributable to comparable relative decreases in the trunk (12%, 3.8 kg) and
      immobilized limb (13%, 1.4 kg) whereas the nonimmobilized limb exhibited smaller
      declines (7%, 0.8 kg). In Weeks 8 to 24, the athlete adhered to a moderate
      carbohydrate-high protein diet combined with structured resistance and field
      based training for both the lower and upper-body that resulted in whole-body
      muscle hypertrophy (varying from 0.5 to 1 kg per week). Regional hypertrophy was
      particularly pronounced in the trunk and nonimmobilized limb during weeks 8 to 12
      (2.6 kg) and 13 to 16 (1.3 kg), respectively, whereas the previously immobilized
      limb exhibited slower but progressive increases in lean mass from Week 12 to 24
      (1.2 kg). The athlete presented after the totality of the injured period with an
      improved anthropometrical and physical profile. 

PMID- 24458223
TI  - Impact of macrolide therapy in patients hospitalized with Pseudomonas aeruginosa
      community-acquired pneumonia.
AB  - BACKGROUND: Several studies have described a clinical benefit of macrolides due
      to their immunomodulatory properties in various respiratory diseases. We aimed to
      assess the effect of macrolide therapy on mortality in patients hospitalized for
      Pseudomonas aeruginosa community-acquired pneumonia (CAP). METHODS: We performed
      a retrospective population-based study of > 150 hospitals in the US Veterans
      Health Administration. Patients were included if they had a diagnosis of CAP and
      P aeruginosa was identified as the causative pathogen. Patients with health-care
      associated pneumonia and immunosuppression were excluded. Macrolide therapy was
      considered when administered within the first 48 h of admission. Univariate and
      multivariable analyses were performed using 30-day mortality as the dependent
      measure. RESULTS: We included 402 patients with P aeruginosa CAP, of whom 171
      (42.5%) received a macrolide during the first 48 h of admission. These patients
      were older and white. Macrolide use was not associated with lower 30-day
      mortality (hazard ratio, 1.14; 95% CI, 0.70-1.83; P = .5). In addition, patients
      treated with macrolides had no differences in ICU admission, use of mechanical
      ventilation, use of vasopressors, and length of stay (LOS) compared with patients
      not treated with macrolides. A subgroup analysis among patients with P aeruginosa
      CAP in the ICU showed no differences in baseline characteristics and outcomes.
      CONCLUSIONS: Macrolide therapy in the first 48 h of admission is not associated
      with decreased 30-day mortality, ICU admission, need for mechanical ventilation,
      and LOS in hospitalized patients with P aeruginosa CAP. Larger cohort studies
      should address the benefit of macrolides as immunomodulators in patients with P
      aeruginosa CAP.

PMID- 24458225
TI  - Coalescence of bubbles and drops in an outer fluid.
AB  - When two liquid drops touch, a microscopic connecting liquid bridge forms and
      rapidly grows as the two drops merge into one. Whereas coalescence has been
      thoroughly studied when drops coalesce in vacuum or air, many important
      situations involve coalescence in a dense surrounding fluid, such as oil
      coalescence in brine. Here we study the merging of gas bubbles and liquid drops
      in an external fluid. Our data indicate that the flows occur over much larger
      length scales in the outer fluid than inside the drops themselves. Thus, we find
      that the asymptotic early regime is always dominated by the viscosity of the
      drops, independent of the external fluid. A phase diagram showing the crossovers
      into the different possible late-time dynamics identifies a dimensionless number
      that signifies when the external viscosity can be important. 

PMID- 24458226
TI  - Risk factors for prophylactic proximal aortic replacement in the current era.
AB  - BACKGROUND: Decision-making in aortic aneurysm involves careful weighing of
      spontaneous prognosis and operative risk. There is limited recent information
      regarding operative risk and risk factors using current surgical strategies.
      METHODS: From 1998 to 2010, 1,221 patients (60 +/- 15 years, 67 % male) underwent
      elective proximal aortic replacement (286 ascending aortic replacement, 699
      concomitant root and 387 concomitant arch replacement). Additional cardiac
      procedures were necessary in 48 %. Previous cardiovascular operations had been
      performed in 9.6 % (aortic valve 6.3 %, ascending aorta 2.9 %, coronary artery
      bypass grafting 2.2 %). RESULTS: Early mortality was 4.2 % overall; it was 2.6 %
      for isolated aortic replacement as primary surgery. In patients younger than 70
      years (n = 829), mortality was 2.4 % overall and 1.2 % for isolated and primary
      surgery; it was 7.9 and 6.4 %, respectively, in patients >= 70 years. Mortality
      was not significantly influenced by root replacement (P = 0.13) or arch
      replacement (P = 0.27). Multiple logistic regression analysis identified higher
      age (P < 0.01), chronic aortic dissection (P < 0.01), history of previous
      cardiovascular surgery (P < 0.01), aortic valve stenosis (P = 0.03), and chronic
      renal insufficiency (P = 0.03) as independent predictors for increased early
      mortality. Previous cardiovascular surgery was an independent predictor for
      increased early mortality in patients younger than 70 (P < 0.01), chronic renal
      insufficiency was that in patients >= 70 years (P < 0.01). CONCLUSIONS: Using
      contemporary techniques the risk of proximal aortic replacement is low, in
      particular in younger patients without previous cardiac or aortic surgery. The
      risk is increased in older patients, in particular with chronic renal
      insufficiency. This information should be considered in decision-making for
      prophylactic aortic replacement.

PMID- 24458227
TI  - An attempt to identify single nucleotide polymorphisms contributing to possible
      relationships between personality traits and oxytocin-related genes.
AB  - BACKGROUND: The neuropeptides oxytocin and vasopressin play a central role in
      social behavior. Trials with intranasal oxytocin have been conducted and many
      indicate that the hormone facilitates affiliative behavior and trust. Intranasal
      oxytocin administration is suggested as a treatment option for psychiatric
      illnesses with altered sociability as a core symptom and the effects may be due
      to differences in variants of oxytocin- and vasopressin-related genes. The
      purpose of the present study was to investigate the endogenous oxytocin system by
      exploring the relationship between variants in the oxytocin gene factors and
      personality traits closely related to trust, anxiety and social behavior.
      METHODS: 72 single nucleotide polymorphisms (SNPs) in the genes coding for
      oxytocin (OXT), vasopressin (AVP), the oxytocin receptor (OXTR) and CD38 (CD38),
      including polymorphisms reported earlier to be related to social phenotypes and
      novel SNPs, were investigated in 196 healthy subjects. Association analysis
      between these variants and 3 personality traits (agreeableness, neuroticism and
      extraversion) measured by the Neuroticism-Extraversion-Openness Five-Factor
      Inventory was performed. RESULTS: We found 7 nominally significant associations
      for personality traits: agreeableness [rs857240 (AVP, p = 0.0075), rs2270463
      (OXTR, p = 0.047)], neuroticism [rs3756242 (CD38, p = 0.024), rs13104011 (CD38, p
      = 0.024), rs6816486 (CD38, p = 0.024), rs7655635 (CD38, p = 0.034)] and
      extraversion [rs237878 (OXTR, p = 0.019)]. None of these associations remained
      significant after the Bonferroni correction (p threshold = 2.31 * 10(-4)).
      CONCLUSION: Our results do not contradict the hypothesis of associations between
      personality traits and oxytocin-related gene variants; however, there are no
      statistically significant associations after correcting for multiple testing,
      warranting replication in larger samples.

PMID- 24458228
TI  - Soybean leaf photosynthesis in relation to maturity classification and stage of
      growth.
AB  - Leaf photosynthetic rates were measured on field-grown soybeans during the 1980
      season. Comparisons were made between different cultivars and isolines
      representative of maturity groups I-IV. Mature, fully expanded leaves at
      different nodes on the plant were measured in high light to determine which had
      the highest potential photosynthetic rates at any one time. Successive leaves
      during the growing season had maximum rates which increased from about 22 MU mol
      CO2 m(-2) s(-1) on 25 June to a peak of 30-44 MU mol CO2 m(-2) s(-1) in early
      August.The persistency and eventual decline in the maximum rate was associated
      with the maturity group and related dates of flowering, pod fill and onset of
      senescence. Early maturing cultivars (groups I and II) had higher peak rates (38
      44 MU mol CO2 m(-2) s(-1)) than later maturing cultivars (30-35 MU mol CO2 m(-2)
      s(-1), groups III and IV). However, the photosynthetic rates of early maturing
      cultivars declined rapidly after attaining their peak, whereas the leaves of
      later maturing cultivars maintained their photosynthetic activity for much
      longer. 

PMID- 24458229
TI  - The action of lipases on chloroplast membranes I. The release of plastocyanin
      from galactolipase-treated thylakoid membranes.
AB  - Bean chloroplasts treated with galactolipase (lipolytic acyl hydrolase) isolated
      from bean leaves showed an inhibition of photosystem I activity as measured by
      methyl viologen-mediated oxygen uptake and NADP(+) photoreduction. This
      inhibition was partially reversed by exogenous plastocyanin added to
      galactolipase-treated thylakoid membranes. Galactolipase released substantial
      amounts of endogenous plastocyanin (about 40%) from bean chloroplasts. The
      results are discussed with regard to the localization of plastocyanin in
      thylakoid membranes. 

PMID- 24458230
TI  - Regulation of RuBP carboxylase activity associated with photo-inhibition of
      wheat.
AB  - Detached wheat leaves were illuminated in air until a steady rate of
      photosynthesis was established. Then the gas was changed to 1% O2, 99% N2 and
      after 2.5 h further illumination the capacity of the leaves for photosynthesis in
      air was decreased to approximately 50%. Measurement of RuBP carboxylase activity
      in extracts showed that inhibition of photosynthesis was accompanied by 70%
      inactivation of this enzyme. The capacity for photosynthesis and the activity of
      RuBP carboxylase were recovered when leaves were returned to normal air. Extracts
      of the leaves made when photosynthesis and carboxylase activity were low,
      recovered most of the lost carboxylase activity when supplemented with
      bicarbonate and magnesium ions. The time courses for activation and inactivation
      of the RuBP carboxylase in these experiments suggests the operation of a
      mechanism that has not yet been elucidated. 

PMID- 24458231
TI  - Photosynthesis, photosynthetic enzymes and leaf area development in relation to
      hybrid vigour in Sorghum vulgare L.
AB  - Heterotic hybrids of sorghum produced more dry matter than their respective
      parents. Therefore, an analysis of leaf are development, rate of photosynthesis
      and activities of RuBP carboxylase and PEP carboxylase was made to determine
      whether the superior dry matter production in the hybrids could be attributed to
      any of these characteristics. Heterosis in leaf area was maintained at all stages
      in plant growth. Heterosis in photosynthesis was observed only during grain
      development in certain hybrids. At all other stages, the photosynthesis rate in
      hybrids were either intermediate or similar to one of the parents. No heterotic
      effect was observed in enzyme activity at any stage of growth. It is suggested
      that a multiplicative interaction between the heterotic leaf area and
      photosynthesis rate could possibly explain heterosis in dry matter production in
      heterotic hybrids. 

PMID- 24458232
TI  - The relationship between cation-induced fluorescence and membrane stacking in
      isolated spinach chloroplasts.
AB  - In order to study the relationship between Mg(++)-induced fluorescence and
      membrane stacking, trypsin was used as a probe. Trypsin treatment diminished to a
      high degree the light-induced variable fluorescence and membrane stacking. Mg(++)
      markedly increased the fluorescence yield near 680 nm and membrane stacking.
      Pretreatment of chloroplasts with Mg(++) eliminates the effect of trypsin on
      cation-induced fluorescence change but not on the membrane stacking. The results
      presented in this contribution support the evidence that the cation-induced
      membrane stacking and the fluorescence yield are not linked. 

PMID- 24458233
TI  - Isolation and purification of membrane-bound cytochrome b-560 from photosynthetic
      bacterium Chromatium vinosum.
AB  - A membrane-bound cytochrome of the b-type (cytochrome b-560) was success-fully
      purified from chromatophores of the photosynthetic purple sulfur bacterium
      Chromatium vinosum by treatment with sodium cholate, sodium deoxycholate, sodium
      thiocyanate, and bacterial alkaline protease (EC 3.4.21.14) followed by gel
      filtration.The purified cytochrome b-560 showed the absorption maxima at 279,
      412.5 and 533 nm in the oxidized form, and 427, 530 and 560 nm in the reduced
      form. Reduced-minus-oxidized difference millimolar absorption coefficient was
      14.0 for a wavelength pair, 560 minus 540 nm.Isolated cytochrome b-560 was
      electrophoretically homogeneous, and its minimal molecular weight was estimated
      to the 13,000 by SDS polyacrylamide gel electrophoresis.The midpoint potential at
      pH 8.0 was -110mV, and was not dependent on the ambient pH in the pH range of 6.8
      to 8.8. 

PMID- 24458234
TI  - A new infra-red gas analyser and portable photosynthesis meter.
AB  - The new infra-red gas analyser for measurement of CO2 concentration described
      uses a focussed, dual optical path. The 2W radiation source is a heated alumina
      bead and a cooled lead selenide photoconductive detector measures the difference
      in radiation absorption at 4.26 MUm by the gas in sample and reference tubes.
      Radiation is chopped alternately between these tubes at 120 Hz. The signal from
      the detector is processed through an a.c. coupled amplifier, phase sensitive
      detector and low pass filter. Incorporated into the photosynthesis meter, the
      sample tube of the analyser is connected to a leaf chamber and circulating pump
      forming a closed gas circuit. As a leaf in the chamber removes carbon dioxide
      from the air in the closed circuit, the decrease in its concentration is sensed
      by the analyser. The time taken for the concentration to decrease by a
      predetermined amount (typically 30 ppm) is displayed and rate of net
      photosynthesis can be calculated from this and the volume of the closed circuit.
      A measurement of the light-saturated rate of net photosynthesis of a healthy flag
      leaf of wheat can be made in 10-15 seconds. The system is fully portable and has
      been used intensively in the field for two summers. 

PMID- 24458235
TI  - The quantum yield for CO2 uptake in C 3 and C 4 grasses.
AB  - The quantum yield for CO2 uptake was measured in C3 and C4 monocot species from
      several different grassland habitats. When the quantum yield was measured in the
      presence of 21% O2 and 340 cm(3) m(-3) CO2, values were very similar in C3
      monocots, C3 dicots, and C4 monocots (0.045-0.056 mole CO2 . mole(-1) quanta
      absorbed). In the presence of 2% O2 and 800 cm(3) m(-3) CO2, enhancements of the
      quantum yield values occurred for the C3 plants (both monocots and dicots), but
      not for C4 monocots. A dependence of the quantum yield on leaf temperature was
      observed in the C3 grass, Agropyron smithii, but not in the C4 grass, Bouteloua
      gracilis, in 21% O2 and 340 cm(3) m(-3) CO2. At leaf temperatures between 22-25
      degrees C the quantum yield values were approximately equal in the two species. 

PMID- 24458237
TI  - Dye-sensitized solar cells using ethynyl-linked porphyrin trimers.
AB  - Toward the extension of the light-harvesting region of sensitizers in dye
      sensitized solar cells (DSSCs), two ethynyl-linked porphyrin trimers were
      synthesized and investigated. The zinc-freebase-zinc trimer (Zn-FbA-Zn) showed an
      absorption maximum at a longer wavelength than the all-zinc trimer (Zn-ZnA-Zn),
      although the energy level of Zn-FbA-Zn was lower than that of Zn-ZnA-Zn. The
      DSSCs using these trimers showed spectral sensitivities up to 900 nm. Reflecting
      the energy levels of these trimers, the DSSC using Zn-ZnA-Zn showed better
      performance than that using Zn-FbA-Zn. After the optimization of cell fabrication
      conditions, the photoelectric conversion efficiency eta of the DSSC using Zn-ZnA
      Zn reached 3.17%. The larger TiO2 nanoparticles (ca. 37 nm) than the conventional
      cases (ca. 13 nm) were found to be preferable in this case, due to high molar
      extinction coefficients of the porphyrin trimers.

PMID- 24458236
TI  - The fidelity of stochastic single-molecule super-resolution reconstructions
      critically depends upon robust background estimation.
AB  - The quality of super resolution images obtained by stochastic single-molecule
      microscopy critically depends on image analysis algorithms. We find that the
      choice of background estimator is often the most important determinant of
      reconstruction quality. A variety of techniques have found use, but many have a
      very narrow range of applicability depending upon the characteristics of the raw
      data. Importantly, we observe that when using otherwise accurate algorithms,
      unaccounted background components can give rise to biases on scales defeating the
      purpose of super-resolution microscopy. We find that a temporal median filter in
      particular provides a simple yet effective solution to the problem of background
      estimation, which we demonstrate over a range of imaging modalities and different
      reconstruction methods. 

PMID- 24458238
TI  - Simultaneous observation of the metabolism of cisplatin and NAMI-A in human
      plasma in vitro by SEC-ICP-AES.
AB  - Single drug-based cancer therapies are frequently associated with the development
      of drug resistance. To overcome this problem, combination therapy with two or
      more anticancer drugs is a promising strategy, but clinical studies are
      logistically challenging and costly. Intermediary in vitro studies, however, can
      provide critical insight to decide whether one should proceed to in vivo studies.
      To this end, cisplatin and the Ru-based anticancer drug NAMI-A were added to
      human plasma and the size distribution of Pt-containing and Ru-containing
      entities was determined over a 2 h period. The results revealed a dramatically
      different rate of plasma protein binding for each drug and/or their hydrolysis
      products. Both drugs bound to the same apparent plasma proteins, but crucially
      they did not adversely affect each other's metabolism. Therefore, combination
      therapy of patients with these metallodrugs should be further assessed in
      clinical studies in order to systematically develop an effective combination
      therapy protocol to prevent the resurgence of cancer.

PMID- 24458239
TI  - Primary cardiac tumours in the paediatric population.
AB  - Primary cardiac tumours are relatively rare in the paediatric population, and
      they may occur with different signs and symptoms in foetal or post-natal life.
      The clinical manifestations of cardiac tumours in foetal life may include
      arrhythmias, congestive heart failure and hydrops. In post-natal life, cardiac
      tumours may cause cyanosis, respiratory distress, myocardial dysfunction,
      valvular insufficiency, arrhythmias, inflow or outflow tract obstructions and
      sudden death. Surgical treatment is essential when symptoms are present, while
      the role of medical therapy can merely be palliative. Results are various and
      related to the patients' and tumour characteristics. Primary benign heart tumours
      mainly have a good prognosis, while malignant neoplasms usually have a poor
      prognosis; in both cases, however, a strict follow-up is always mandatory in
      order to detect the recurrence of cardiac neoplasms after surgery. 

PMID- 24458240
TI  - One-step surgery with multipotent stem cells for the treatment of large full
      thickness chondral defects of the knee.
AB  - BACKGROUND: Chondral lesions in athletically active patients cause considerable
      morbidity, and treatment with existing cell-based therapies can be challenging.
      Bone marrow has been shown as a possible source of multipotent stem cells (MSCs)
      with chondrogenic potential and is easy to harvest during the same surgical
      procedure. PURPOSE: To investigate the clinical outcome in a group of active
      patients with large full-thickness chondral defects of the knee treated with 1
      step surgery using bone marrow-derived MSCs and a second-generation matrix. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: From January 2007 to February
      2010, 25 patients (average age, 46.5 years) with symptomatic large chondral
      defects of the knee (International Cartilage Repair Society grade 4) who
      underwent cartilage transplantation with MSCs and a collagen type I/III matrix
      were followed up for a minimum of 3 years. The average lesion size was 8.3 cm(2).
      Coexisting injuries were treated during the same surgical procedure in 18
      patients. All patients underwent a standard postoperative rehabilitation program.
      Preoperative and postoperative evaluations at 1-year, 2-year, and final follow-up
      included radiographs, magnetic resonance imaging (MRI), and visual analog scale
      (VAS) for pain, International Knee Documentation Committee (IKDC), Knee injury
      and Osteoarthritis Outcome Score (KOOS), Lysholm, Marx, and Tegner scores. Seven
      patients underwent second-look arthroscopic surgery, with 4 consenting to a
      tissue biopsy. RESULTS: No patients were lost at final follow-up. The average
      preoperative values for the evaluated scores were significantly improved at final
      follow-up (P < .001): VAS, 5.4 +/- 0.37 to 0.48 +/- 0.19; IKDC subjective, 37.92
      +/- 4.52 to 81.73 +/- 2.42; KOOS pain, 61.04 +/- 3.95 to 93.32 +/- 1.92; KOOS
      symptoms, 55.64 +/- 3.23 to 89.32 +/- 2.32; KOOS activities of daily living,
      63.96 +/- 4.48 to 91.20 +/- 2.74; KOOS sports, 34.20 +/- 5.04 to 80.00 +/- 3.92;
      KOOS quality of life, 32.20 +/- 4.43 to 83.04 +/- 3.37; Lysholm, 46.36 +/- 2.25
      to 86.52 +/- 2.73; Marx, 3.00 +/- 0.79 to 9.04 +/- 0.79; and Tegner, 2.12 +/-
      0.32 to 5.64 +/- 0.26. Patients younger than 45 years of age and those with
      smaller or single lesions showed better outcomes. The MRI scans showed good
      stability of the implant and complete filling of the defect in 80% of patients,
      and hyaline-like cartilage was found in the histological analysis of the biopsied
      tissue. No adverse reactions or postoperative complications were noted.
      CONCLUSION: The treatment of large chondral defects with MSCs is an effective
      procedure and can be performed routinely in clinical practice. Moreover, it can
      be achieved with 1-step surgery, avoiding a previous surgical procedure to
      harvest cartilage and subsequent chondrocyte cultivation.

PMID- 24458241
TI  - Does degree of trochlear dysplasia and position of femoral tunnel influence
      outcome after medial patellofemoral ligament reconstruction?
AB  - BACKGROUND: The medial patellofemoral ligament (MPFL) is the main restraining
      force against lateral patellar displacement. It is disrupted after patellar
      subluxation or dislocation. Reconstruction of the MPFL is frequently performed
      when nonoperative management fails and the patient experiences recurrent patellar
      dislocation. PURPOSE: To determine the relationship between the degree of
      trochlear dysplasia and femoral tunnel position and outcome after MPFL
      reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total
      of 68 patients (72 knees) with recurrent dislocation of the patella underwent
      MPFL reconstruction. The mean follow-up was 31.3 months (range, 13-72 months).
      Clinical and functional outcomes were recorded using the Kujala, Lysholm, and
      Tegner scores. Postoperative complications, participation in sporting activity,
      and overall patient satisfaction were determined. Radiographs were analyzed to
      evaluate congruence angle, lateral patellofemoral angle, patellar height,
      trochlear dysplasia, trochlear boss height, and position of the femoral tunnel.
      RESULTS: The mean Kujala, Lysholm, and Tegner scores postoperatively were 76.2,
      73.8, and 3.6, respectively (n = 61). The mean congruence angle (n = 30) improved
      from 22.5 degrees  to 1.0 degrees  postoperatively (P = .000038), the lateral
      patellofemoral angle (n = 30) improved from 7.4 degrees  to 7.8 degrees 
      postoperatively (P = .048), and the patellar height (n = 46) using the Caton
      Deschamps method improved from 1.1 to 1.0 postoperatively (P = .000016). Mild
      trochlear dysplasia grade A/B was found in 89% of patients (n = 54), and 11% of
      patients (n = 7) had severe grade C/D dysplasia. The mean distance from the
      anatomic insertion of the MPFL to the center of the tunnel was 9.3 mm (range, 0.5
      28.2 mm), with 71.7% thought to be within 10 mm of the anatomic position defined
      by Schottle (n = 46). When patients with high-grade trochlear dysplasia were
      excluded, anatomically placed femoral tunnels demonstrated significantly better
      clinical scores than did tunnels not placed anatomically (Kujala score, P = .028;
      Lysholm score, P = .012). A multivariate logistic regression analysis also
      demonstrated that the distance of the femoral tunnel from the anatomic position
      predicted clinical outcome (Kujala score, P = .043; Lysholm score, P = .028). All
      of the patients with severe trochlear dysplasia (n = 7) suffered from recurrent
      dislocations postoperatively, compared with only 9.3% of patients (n = 5) with
      mild trochlear dysplasia (P = .0001). Four patients had patellar fractures
      postoperatively. Of patients with mild dysplasia, 83% were either very satisfied
      or satisfied with the outcome of their surgery compared with only 57% with severe
      dysplasia (P = .05). Of patients with mild trochlear dysplasia, 56% returned to
      sport postoperatively compared with only 43% of patients with severe trochlear
      dysplasia (P = .526). CONCLUSION: This study demonstrates the importance of
      restoration of the anatomic insertion point of the MPFL when performing MPFL
      reconstruction and proposes that this procedure should not be performed in
      isolation in patients with high-grade trochlear dysplasia.

PMID- 24458242
TI  - Matching articular surfaces of selected donor and recipient sites for cylindrical
      osteochondral grafts of the femur: quantitative evaluation using a 3-dimensional
      laser scanner.
AB  - BACKGROUND: Autogenous osteochondral grafting has been widely performed as a
      treatment for focal osteochondral defects. In this procedure, it is important to
      match the shape of the articular surface between the donor site and recipient
      site to reproduce the original articular surface of the femur. PURPOSE: To
      investigate the ideal matching patterns of articular surface profiles of donor
      and recipient sites for autogenous osteochondral grafting of the femur using a 3
      dimensional laser scanning method. STUDY DESIGN: Descriptive laboratory study.
      METHODS: The donor and recipient sites in 11 cadaveric knees were examined, and
      each of the sites was divided into 12 areas. In the donor sites, the contours of
      the articular surface of the medial and lateral femoral trochleae were
      determined. In the recipient sites, the contours of the articular surface of the
      medial and lateral femoral condyles were assessed. Vertical intervals (VIs) were
      then calculated as the parameter for the height of the articular surface. The VI
      was the height difference from the highest and lowest points in the contours of
      the articular surface within the area of the donor and recipient sites. Finally,
      assessments were made on whether the articular surface of the donor and recipient
      sites matched properly for cylindrical osteochondral grafts with diameters of 6,
      8, and 10 mm. RESULTS: For the donor site, the VIs of the middle area of the
      femoral trochlea were significantly smaller than those of the peripheral area.
      For the recipient site, the VIs of the anterior area of the femoral condyle were
      significantly smaller than those of the posterior area. CONCLUSION: These results
      indicated in aging specimens that the articular surface profile of the middle
      area of the donor site matched that of the anterior area of the recipient site.
      On the other hand, the shape of the articular surface of the peripheral area of
      the donor site was congruent with that of the posterior area of the recipient
      site. CLINICAL RELEVANCE: This study will be useful for improving donor site
      selection during preoperative planning. The authors recommend selection of the
      middle area of the femoral trochlea for cartilage defects in the anterior area of
      the femoral condyle and of the peripheral area of the femoral trochlea for
      cartilage defects in the posterior area of the femoral condyle.

PMID- 24458243
TI  - Effects of the synthetic estrogen 17alpha-ethinylestradiol on aromatase
      expression, reproductive behavior and sperm quality in the fish Jenynsia
      multidentata.
AB  - The synthetic estrogen 17alpha-ethynylestradiol (EE2) has been increasingly
      detected in sewage effluents in the last two decades. The aim of the present
      study was determined if EE2 exposure adversely affected reproduction in
      internally fertilizing fish species Jenynsia multidentata. Sexual behavior, brain
      and gonadal aromatase expression as well as sperm quality were evaluated. The
      brain aromatase expression, reproductive behavior, spermatozoa viability and
      gonadosomatic index were sensitive biomarkers of EE2 effects on this species. The
      condition factor, hepatosomatic index, gonadal aromatase expression, sperm count
      and sperm velocities were unaltered after EE2 exposure. The present work
      highlights the importance of using a combination of several biomarkers to study
      the effects of estrogenic compounds, especially when trying to link these results
      to potential population-level effects. 

PMID- 24458244
TI  - Mercury concentrations in tissues of Colombian slider turtles, Trachemys
      callirostris, from northern Colombia.
AB  - This study determined the total mercury (THg) concentrations in pectoral muscle,
      blood and carapace tissue in turtles collected from Magangue and Lorica,
      Colombia. THg concentrations in MUg/g (wet weight) were 0.39 +/- 0.16 in muscle,
      0.15 +/- 0.08 in carapace and 0.07 +/- 0.03 in blood for turtles from the
      Magdalena River and 0.25 +/- 0.18 in muscle, 0.14 +/- 0.09 in carapace and 0.06
      +/- 0.04 in blood for turtles from the Sinu River. Twenty-nine and ten percent of
      turtle muscle samples from Magangue and Lorica, respectively, exceeded the
      consumption advisory limit of 0.5 MUg Hg/g for fish. There was a significant
      correlation between carapace length and THg levels for this specie, depending on
      the sample site. In addition, a significant correlation was observed in THg
      concentrations in carapace and muscle. However, significant differences were
      observed in the THg levels between the two study locations, with turtles caught
      in the Magdalena River having higher levels of THg. 

PMID- 24458245
TI  - Characteristics of toxic metal accumulation in farmland in relation to long-term
      chicken manure application: a case study in the Yangtze River Delta Region,
      China.
AB  - Characteristics of toxic metal accumulation in farmland in relation to intensive
      chicken manure application on a regional scale was studied in this paper.
      Concentrations of Zn, As and Cu in manure exceeded the related standard in 66.7%,
      14.3% and 16.7% of samples, respectively. Among chicken feed samples,
      concentrations of Zn, Cr and As exceeded the National Standard limits in 74.3%,
      56.3% and 34.3% of samples, respectively. The accumulation of metals in soils
      from long-term chicken manure application has led to increasing uptake in above
      ground shoots of wheat. The maximum contents of all metals present in the soil
      are currently below the threshold values of National Grade II criteria. At
      present, the farmland soil is safe for agricultural production, but more
      attention should be given to the potential environmental risk of metal
      accumulation in chicken manure and soils.

PMID- 24458246
TI  - Persistence of 2,4-D and its effects on benthic macroinvertebrates following
      spring treatment of Eurasian Watermilfoil, Myriophyllum spicatum L. in two lakes
      in southeastern Wisconsin, USA.
AB  - The purpose of this study was to determine the persistence of 2,4
      dichlorophenoxyacetic acid (2,4-D) applied to two lakes (one mesotrophic and one
      eutrophic) for the control of Eurasian watermilfoil (EWM), and to determine the
      impacts of 2,4-D on benthic macroinvertebrates in one of the lakes. One lake was
      treated with a liquid formulation, and the other with a slow release granular
      formulation of 2,4-D. Concentrations of 2,4-D in the water column were highest 1
      and 2 days post-treatment and declined to below detection limits by 7 and 10 days
      post-treatment. We observed negative correlations between days post-treatment and
      taxa richness, and between days post-treatment and abundance of three of 12
      taxonomic groups of macroinvertebrates. Lake managers need to balance control of
      EWM with possible impacts of 2,4-D to nontarget organisms.

PMID- 24458247
TI  - Isolation and identification of hexazinone-degrading bacterium from sugarcane
      cultivated soil in Kenya.
AB  - The s-triazine herbicide hexazinone [3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5
      triazine-2,4(1H,3H)-dione], is widely used in agriculture for weed control.
      Laboratory biodegradation experiments for hexazinone in liquid cultures were
      carried out using sugarcane-cultivated soils in Kenya. Liquid culture experiments
      with hexazinone as the only carbon source led to the isolation of a bacterial
      strain capable of its degradation. Through morphological, biochemical and
      molecular characterization by 16S rRNA, the isolate was identified as
      Enterobacter cloacae. The isolate degraded hexazinone up to 27.3% of the
      initially applied concentration of 40 MUg mL(-1) after 37 days of incubation in a
      liquid culture medium. The study reports the degradation of hexazinone and
      characterization of the isolated bacterial strain.

PMID- 24458249
TI  - The role of regucalcin in bone homeostasis: involvement as a novel cytokine.
AB  - Regucalcin, which was discovered as a calcium-binding protein in 1978, has been
      demonstrated to play a multifunctional role in the regulation of various tissues
      and cell types. Regucalcin plays a pivotal role in the regulation of
      intracellular calcium homeostasis, various enzyme activities, cell signal
      transduction, nuclear function and gene expression, and cell proliferation and
      apoptosis. Moreover, regucalcin has been found to play a role in the regulation
      of bone homeostasis. Overexpression of regucalcin induces bone loss in regucalcin
      transgenic rats in vivo and deficiency causes osteomalacia in vivo. Regucalcin
      mRNA and its protein are expressed in rat femoral tissues, bone marrow cells, and
      osteoblastic cells. Exogenous regucalcin has suppressive effects on the
      differentiation and mineralization of osteoblastic MC3T3-E1 cells and stimulates
      osteoclastogenesis in mouse bone marrow culture in vitro. Moreover, regucalcin
      has been found to suppress osteoblastogenesis and stimulate adipogenesis in the
      bone marrow culture system in vitro. Regucalcin shows enhancing effects on
      activation of NF-kappaB, which is mediated through tumor necrosis factor-alpha
      (TNF-alpha) or the receptor activator of the NF-kappaB ligand (RANKL) in
      preosteoblastic cells and preosteoclastic cells. Exogenous regucalcin may play a
      pivotal role in the regulation of bone homeostasis as a suppressor in
      osteoblastogenesis and an enhancer in osteoclastogenesis, suggesting its role as
      a cytokine. 

PMID- 24458248
TI  - Genetic alterations in chondrosarcomas - keys to targeted therapies?
AB  - BACKGROUND: Chondrosarcomas are malignant tumors of chondrocytes and represent
      the second most common type of primary bone tumors. Within the context of normal
      chondrogenesis, this review summarizes results from recent research outlining the
      key molecular changes that occur during the development of this sarcoma type.
      RESULTS: Current data support the notion that a two-hit scenario, common to many
      tumors, also underlies chondrosarcoma formation. First, early-stage mutations
      alter the normal proliferation and differentiation of chondrocytes, thereby
      predisposing them to malignant transformation. These early-stage mutations, found
      in both benign cartilaginous lesions and chondrosarcomas, include alterations
      affecting the IHH/PTHrP and IDH1/IDH2 pathways. As they are not observed in
      malignant cells, mutations in the EXT1 and EXT2 genes are considered early-stage
      events providing an environment that alters IHH/PTHrP signaling, thereby inducing
      mutations in adjacent cells. Due to normal cell cycle control that remains
      active, a low rate of malignant transformation is seen in benign cartilaginous
      lesions with early-stage mutations. In contrast, late-stage mutations, seen in
      most malignant chondrosarcomas, appear to induce malignant transformation as they
      are not found in benign cartilaginous lesions. These late-stage mutations
      primarily involve cell cycle pathway regulators including p53 and pRB, two genes
      that are also known to be implicated in numerous other human tumor types.
      CONCLUSIONS: Now the key genetic alterations involved in both early and late
      stages of chondrosarcoma development have been identified, focus should be
      shifted to the identification of druggable molecular targets for the design of
      novel chondrosarcoma-specific therapies.

PMID- 24458250
TI  - Response to warfarin therapy in obese pediatric patients dosed according to
      institutional guidelines.
AB  - BACKGROUND: Current warfarin dosing guidelines for pediatric patients do not
      account for obesity. Published data from adults suggest that obesity may affect
      warfarin dosing requirements. Obesity is prevalent in the pediatric population,
      and current warfarin dosing methods should be evaluated in obese pediatric
      patients. METHODS: Patients aged 2 to 18 years who were obese and initiated on
      warfarin therapy at our institution as inpatients from 2004 to 2010 were
      identified and matched in a 1:2 ratio by age and sex with nonobese patients who
      were initiated on warfarin therapy. Patients were categorized obese per Centers
      for Disease Control guidelines. Demographic and disease state information,
      warfarin dosing information, INR values, and interacting medications were
      collected. Warfarin was dosed according to the institutional guidelines adapted
      from the published literature. Time to therapeutic INR value was the primary
      endpoint and percent of patients with supratherapeutic INR values was the
      secondary endpoint. RESULTS: A total of 30 patients met the study criteria (10
      obese, 20 nonobese), and baseline demographic variables were similar. No
      significant differences were noted in the number of INR values drawn, number of
      warfarin doses administered, or length of stay. Initial and maximum doses of
      warfarin per kg were significantly lower in obese patients compared with nonobese
      patients (P<0.05). Median time to therapeutic INR value was twice as long in
      obese patients as in nonobese patients (median=6 [range, 4 to 28 d] versus
      median=3 [range, 1 to 10 d]; P<0.01). CONCLUSIONS: Obese pediatric patients have
      an increased time to therapeutic INR value when traditional warfarin dosing
      guidelines are used.

PMID- 24458251
TI  - Catalytic enantioselective trifluoromethylthiolation of oxindoles using shelf
      stable N-(trifluoromethylthio)phthalimide and a cinchona alkaloid catalyst.
AB  - The organocatalytic enantioselective trifluoromethylthiolation of oxindoles
      employing N-(trifluoromethylthio)phthalimide as a stable, easy to handle CF3S
      source has been developed. Optically active products with a quaternary
      stereogenic center bearing a CF3S-group are obtained in good yields and with good
      to excellent enantioselectivities. 

PMID- 24458253
TI  - Regulation of aging in flowers of Ipomoea tricolor by ethylene.
AB  - Flowers of Ipomoea tricolor Cav. open early in the morning and fade in the
      afternoon of the same day. Senescence, as manifested by curling-up of the corolla
      and by increase in RNase activity, can be induced prematurely by treatment with
      ethylene (C2H4). Conversely, aging of the flower can be delayed by treatment with
      CO2 or by absorption of endogenously produced C2H4 with mercuric perchlorate.
      C2H4 given for 20 or 40 min and removed before any signs of senescence can be
      observed also advances the onset of aging. In untreated flowers, fading of the
      corolla coincides with a sharp increase in the rate of endogenous C2H4
      production. A 60-min treatment with C2H4 induces an immediate increase in the
      rate of endogenous C2H4 formation. A model is proposed to explain the mechanism
      by which C2H4 may induce C2H4 synthesis. 

PMID- 24458254
TI  - The effect of colchicine on colony formation in the algae Hydrodictyon,
      Pediastrum and Sorastrum.
AB  - Uninucleate, biflagellate zoospores of Hydrodictyon, Pediastrum and Sorastrum,
      derived from multinucleate parental cells, aggregate and adhere to form
      distinctively patterned colonies; earlier work has shown that microtubules
      underlie the plasmalemma of these zoospores and are also conspicuous in the
      developing horns of aggregating cells of Pediastrum and Sorastrum. Colchicine
      applied to parental cells inhibited cytoplasmic cleavage and production of
      uninucleate zoospores. When zoospores were treated with colchicine, their
      peripheral microtubules disappeared; the spores failed to aggregate in ordered
      arrays and did not develop horns. The microtubules therefore appear to play an
      important role in determining the arrangement of cells in developing colonies by
      affecting the shape of the cells at the time of their aggregation. 

PMID- 24458255
TI  - The rapid non-polar transport of auxin in the phloem of intact Coleus plants.
AB  - Indole-3-acetic acid (IAA) is transported from a nearly mature leaf throughout an
      intact Coleus blumei Benth. plant in the phloem. A buffered solution of both
      (14)C-methylene-labeled indoleacetic acid ([(14)C]IAA) and [6-(3)H]glucose was
      supplied in a glass capillary to the distal end of a severed main lateral vein of
      the leaf. Both labeled sugar and auxin move rapidly through the plant at
      velocities of ca. 16-20 cm h(-1) with closely similar, exponential profiles. This
      translocation is nonpolar; both auxin and sugar move upwards to the apex and
      young expanding leaves as well as downwards to the base of the shoot. Neither
      tracer appears in mature leaves; this eliminates the possibility that they enter
      the xylem. At the end of the transport period, 80-90% of the radioactivity
      recovered from various portions of the plants supplied with [(14)C]IAA is still
      identical chromatographically with IAA. In microautoradiographs prepared by
      techniques that minimize loss and redistribution of soluble compounds,
      radioactivity from [(3)H]IAA is concentrated in the phloem of the midrib and
      petiole of the fed leaf. A ring of triiodobenzoic acid (TIBA) strongly inhibits
      the polar auxin transport in sections isolated from the ringed region but does
      not significantly affect auxin translocation in the phloem of intact plants. TIBA
      does, however, reduce the entry of auxin into the collecting veins of the leaf.
      Thus steps in auxin transport sensitive to TIBA may occur during transfer through
      the leaf or into the phloem, but not during long distance translocation in the
      phloem. 

PMID- 24458256
TI  - Hormones and metabolites which control tracheid differentiation, with or without
      concomitant effects on growth, in cultured tuber tissue of Helianthus tuberosus
      L.
AB  - When tuber slices of Helianthus tuberosus, are cultured in liquid media
      containing minerals, thiamine, 2% sucrose, and 1 mg/l alpha-naphthalene acetic
      acid (NAA) for 14 days, 3-5% of the cells differentiate into tracheids. Addition
      of benzylaminopurine (BAP) at 5 mg/l, and 4% starch, which act as xylogenic
      stimuli, has little effect on growth but results in a yield of over 30% tracheids
      in the same time period. 70-80% of the tracheids appear between days 8 and 14 of
      culture. Addition to optimal tracheid media of gibberellic acid (GA3) or abscisic
      acid (ABA) inhibits tracheid differentiation by 80-90%. GA3 causes a concomitant
      20-40% reduction in total cell number while ABA has no effect on growth. In media
      containing only NAA (lacking BAP and starch), ABA has a large stimulatory effect
      on the rate of cell division, producing 50% more cells than controls. Sucrose and
      glucose are equally effective sugars for differentiation, but use of the two in
      combination results in an unusual interaction leading to substantial inhibition
      of tracheid formation. There is some indication that the high level of BAP
      required in tracheid differentiation is acting only at the first regulatory step
      controlling formation of provascular cells, and not in later steps of cellular
      development. 

PMID- 24458257
TI  - Lysine-methionine-threonine interactions in growth and development of Mimulus
      cardinalis seedlings.
AB  - Plants of Mimulus cardinalis Douglas (Scrophulariaceae) were grown in axenic
      culture from seed for 28 days on a minimal salts medium supple-mented with L
      lysine, L-methionine, L-threonine, L-isoleucine, DL-or L-homoserine or DL
      homocysteine, alone or in combinations ranging from 5 to 1000 MUM. Abnormal
      growth was observed at the higher concentrations of all these aminoacidsexcept
      homocysteine. The lysine inhibition was significantly reduced by methionine,
      homocysteine or isoleucine. The threonine inhibition was significantly reduced by
      methionine or homocysteine. A combination of lysine and threonine at 1 MM was
      lethal. This synergistic effect was prevented when methionine, homoserine or
      homocysteine were added to the lysine-threonine combination. These results can be
      explained in terms of end-product control of aspartokinase and homoserine
      dehydrogenase by lysine and threonine, respectively, in the biosynthetic pathway
      to these aspartic-acid-derived amino acids. 

PMID- 24458258
TI  - [Sucrose metabolizing enzymes in roots].
AB  - In tomato, pea, and maize roots, the presence of sucrose synthetase (E.C.
      2.4.1.13), sucrose phosphate synthetase (E.C. 2.4.1.14), and both the alkaline
      and acid sucrases (E.C. 3.2.1.? and E.C. 3.2.1.26) could be demonstrated. The
      activity of these enzymes was measured directly on root slices suspended in the
      incubation mixture, which also contained 10% dimethyl sulfoxide or 5% ethyl
      acetate. These two additives increase the permeability of the membranes, thus
      allowing the entry of substrates to the site where the enzymes are located and
      favouring the release of products into the medium. The values found by measuring
      the activities of sucrose synthetase and the alkaline sucrase on tomato root were
      quite comparable to those obtained using enzymic preparations of the same tissue.
      In the case of the weakly active sucrose phosphate synthetase and the very active
      acid sucrase, the comparison of the two methods showed that losses of activity
      occurred during the preparation of the enzymes. By separating stele from cortex
      in tomato and maize roots, it could be shown that sucrose phosphate synthetase is
      located only in the stele, while the other enzymes are unevenly distributed
      between the two tissues, the sucrases predominating in the cortex. Sucrose
      phosphate synthetase and sucrose synthetase are most active in the region with
      root hairs of maize roots, while the activity of both sucrases is higher in the
      region near the apex. The highest invertase activity was measured in the apex of
      stem-borne adventitious roots that had not yet penetrated the soil. In older
      roots, sucrose phosphate synthetase disappears and the activity of all the other
      enzymes diminishes. It is suggested that the high activity of sucrose synthetase
      is present in the regions where an active synthesis of cell wall substances from
      glycosyl nucleotides is taking place, while the sucrases provide the initial
      substrates for most of the other pathways. 

PMID- 24458259
TI  - The role of lipases in the germination of dormant apple embryos.
AB  - Changes in the activity of alkaline and acid lipases were studied during the
      culture of embryos isolated from dormant apple (Pyrus malus L.) seeds. Light and
      treatment with gibberellins (GAs) and with AMO-1618, an inhibitor of GA
      biosynthesis, influenced the activity of both enzymes. In dark-grown embryos the
      activity of the alkaline lipase is stimulated by red irradiation and by treatment
      with GAs, particularly GA4, but is not increased after far-red irradiation or in
      the presence of AMO-1618. In light cultured embryos, it is inhibited by the
      latter compound. Germination of the embryos is affected by the various treatments
      in a similar manner as alkaline lipase activity. These results suggest that light
      stimulates germination of dormant apple embryos by promoting GA4 biosynthesis via
      the phytochrome system; GA4 increases the activity of alkaline lipase, the enzyme
      hydrolysing the storage lipids. Activation of acid lipase by the same factors is
      of a more complicated nature, light, GAs, and AMO-1618 generally causing a
      decrease in the activity of this enzyme. 

PMID- 24458260
TI  - Videomorphometric analysis of hypoxic pulmonary vasoconstriction of intra
      pulmonary arteries using murine precision cut lung slices.
AB  - Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV) - also known as
      von Euler-Liljestrand mechanism - which serves to match lung perfusion to
      ventilation. Up to now, the underlying mechanisms are not fully understood. The
      major vascular segment contributing to HPV is the intra-acinar artery. This
      vessel section is responsible for the blood supply of an individual acinus, which
      is defined as the portion of lung distal to a terminal bronchiole. Intra-acinar
      arteries are mostly located in that part of the lung that cannot be selectively
      reached by a number of commonly used techniques such as measurement of the
      pulmonary artery pressure in isolated perfused lungs or force recordings from
      dissected proximal pulmonary artery segments(1,2). The analysis of subpleural
      vessels by real-time confocal laser scanning luminescence microscopy is limited
      to vessels with up to 50 um in diameter(3). We provide a technique to study HPV
      of murine intra-pulmonary arteries in the range of 20-100 um inner diameters. It
      is based on the videomorphometric analysis of cross-sectioned arteries in
      precision cut lung slices (PCLS). This method allows the quantitative measurement
      of vasoreactivity of small intra-acinar arteries with inner diameter between 20
      40 um which are located at gussets of alveolar septa next to alveolar ducts and
      of larger pre-acinar arteries with inner diameters between 40-100 um which run
      adjacent to bronchi and bronchioles. In contrast to real-time imaging of
      subpleural vessels in anesthetized and ventilated mice, videomorphometric
      analysis of PCLS occurs under conditions free of shear stress. In our
      experimental model both arterial segments exhibit a monophasic HPV when exposed
      to medium gassed with 1% O2 and the response fades after 30-40 min at hypoxia.

PMID- 24458261
TI  - A phase 1, open-label, dose-escalation study of BIIB022 (anti-IGF-1R monoclonal
      antibody) in subjects with relapsed or refractory solid tumors.
AB  - PURPOSE: The IGF-1R signaling pathway has been implicated in multiple cancers as
      important for cell survival, proliferation, invasion and metastasis. BIIB022 is a
      non-glycosylated human IgG4 monoclonal antibody (mAb) with specificity for IGF
      1R. Unlike other anti-IGF1R antibodies, BIIB022 has no effector functions.
      Additionally, inhibition is via an allosteric rather than competitive mechanism,
      which further differentiates this antibody from others. We sought to determine
      the safety and tolerability of BIIB022 and determine the pharmacokinetic (PK) and
      pharmacodynamic (PD) profile of this antibody. METHODS: A multi-institutional
      phase I study evaluated the safety of escalating doses of BIIB022 given IV q3wk
      until progression or unacceptable toxicity in patients with advanced solid
      tumors. Five sequential BIIB022 dose cohorts were evaluated using a standard 3 +
      3 dose-escalation design (1.5, 5. 10, 20, 30 mg/kg); 10 additional patients were
      treated at the recommended phase 2 dose. RESULTS: 34 patients were treated.
      Toxicities were manageable and mostly low grade; grade 3-4 hyperglycemia was not
      observed. No RECIST responses were observed, although three patients had
      metabolic responses associated with prolonged stable disease. The PK of BIIB022
      was nearly linear in the dose range from 10 to 30 mg/kg, with some nonlinearity
      at lower doses (1.5-5.0 mg/kg), likely due to target-mediated drug disposition of
      BIIB022 at low serum concentrations. PD analyses showed decrease in IGF-1R levels
      on leucocytes, with stable serum values of IGF-1 and IGF-2. CONCLUSIONS: BIIB022
      can be safely given at 30 mg/kg IV every 3 weeks with preliminary evidence of
      biological activity in selected patients.

PMID- 24458263
TI  - Kaempferol derivatives as antiviral drugs against the 3a channel protein of
      coronavirus.
AB  - The protein coded by the open-reading-frame 3a of SARS coronavirus has been
      demonstrated to form a cation-selective channel that may become expressed in the
      infected cell. The activity of the channel is involved in the mechanism of virus
      release. Drugs that inhibit the ion channel can, therefore, inhibit virus
      release, and they could be a source for development of novel therapeutic
      antiviral agents. Various drugs found in Chinese herbs that are well known as
      anticancer agents also have an antiviral potency. Here we tested the flavonols
      kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives
      with respect to their potency to block the 3a channel. We used the Xenopus oocyte
      with a heterologously expressed 3a protein as a model system to test the efficacy
      of the flavonols. Some of these drugs turned out to be potent inhibitors of the
      3a channel. The most effective one was the glycoside juglanin (carrying an
      arabinose residue) with an IC50 value of 2.3 uM for inhibition of the 3a-mediated
      current. Kaempferol derivatives with rhamnose residue also seem to be quite
      effective. We suggest that viral ion channels, in general, may be a good target
      for the development of antiviral agents, and that, in particular, kaempferol
      glycosides are good candidates for 3a channel proteins of coronaviruses. 

PMID- 24458264
TI  - Solvent-induced conformational flexibility of a bicyclic proline analogue:
      Octahydroindole-2-carboxylic acid.
AB  - The conformational preferences of the N-acetyl-N'-methylamide derivatives of the
      four octahydroindole-2-carboxylic acid (Oic) stereoisomers have been investigated
      in the gas-phase and in aqueous solution using quantum mechanical calculations.
      In addition to the conformational effects provoked by the stereochemical
      diversity of Oic, which presents three chiral centers, results provide evidence
      of interesting and rather unusual features. The conformational preferences of the
      Oic stereoisomers in solution are only well described by applying a complete and
      systematic search process, results achieved by simple re-optimization of the gas
      phase minima being very imprecise. This is because the conformational rigidity
      detected in the gas-phase, which is imposed by the chemical restrictions of the
      fused bicyclic skeleton, disappears in aqueous solution, the four stereoisomers
      behaving as flexible molecules in this environment. Thus, in general, the gamma
      turn is the only minimum energy conformation in the gas-phase while in aqueous
      solution the helical, polyproline-II and gamma-turn motifs are energetically
      favored. Molecular dynamics simulations indicate that the conformational
      flexibility predicted by quantum mechanical calculations for the four Oic
      stereoisomers in solution is satisfactorily reproduced by classical force-fields.

PMID- 24458262
TI  - The association between sleep patterns and obesity in older adults.
AB  - BACKGROUND: Reduced sleep duration has been increasingly reported to predict
      obesity. However, timing and regularity of sleep may also be important. In this
      study, the cross-sectional association between objectively measured sleep
      patterns and obesity was assessed in two large cohorts of older individuals.
      METHODS: Wrist actigraphy was performed in 3053 men (mean age: 76.4 years)
      participating in the Osteoporotic Fractures in Men Study and 2985 women (mean
      age: 83.5 years) participating in the Study of Osteoporotic Fractures. Timing and
      regularity of sleep patterns were assessed across nights, as well as daytime
      napping. RESULTS: Greater night-to-night variability in sleep duration and
      daytime napping were associated with obesity independent of mean nocturnal sleep
      duration in both men and women. Each 1 h increase in the standard deviation of
      nocturnal sleep duration increased the odds of obesity 1.63-fold (95% confidence
      interval: 1.31-2.02) among men and 1.22-fold (95% confidence interval: 1.01-1.47)
      among women. Each 1 h increase in napping increased the odds of obesity 1.23-fold
      (95% confidence interval: 1.12-1.37) in men and 1.29-fold (95% confidence
      interval: 1.17-1.41) in women. In contrast, associations between later sleep
      timing and night-to-night variability in sleep timing with obesity were less
      consistent. CONCLUSIONS: In both older men and women, variability in nightly
      sleep duration and daytime napping were associated with obesity, independent of
      mean sleep duration. These findings suggest that characteristics of sleep beyond
      mean sleep duration may have a role in weight homeostasis, highlighting the
      complex relationship between sleep and metabolism.

PMID- 24458265
TI  - Importance of Standardized DXA Protocol for Assessing Physique Changes in
      Athletes.
AB  - PURPOSE: The implications of undertaking DXA scans using best practice protocols
      (subjects fasted and rested) or a less precise but more practical protocol in
      assessing chronic changes in body composition following training and a
      specialized recovery technique were investigated. METHODS: Twenty-one male
      cyclists completed an overload training program, in which they were randomized to
      four sessions per week of either cold water immersion therapy or control groups.
      Whole-body DXA scans were undertaken with best practice protocol (Best) or random
      activity protocol (Random) at baseline, after 3 weeks of overload training, and
      after a 2-week taper. Magnitudes of changes in total, lean and fat mass from
      baseline-overload, overload-taper and baseline-taper were assessed by
      standardization (Deltamean/SD). RESULTS: The standard deviations of change scores
      for total and fat-free soft tissue mass (FFST) from Random scans (2-3%) were
      approximately double those observed in the Best (1-2%), owing to extra random
      errors associated with Random scans at baseline. There was little difference in
      change scores for fat mass. The effect of cold water immersion therapy on
      baseline-taper changes in FFST was possibly harmful (-0.7%; 90% confidence limits
      +/-1.2%) with Best scans but unclear with Random scans (0.9%; +/-2.0%). Both
      protocols gave similar possibly harmful effects of cold water immersion therapy
      on changes in fat mass (6.9%; +/-13.5% and 5.5%; +/-14.3%, respectively).
      CONCLUSIONS: An interesting effect of cold water immersion therapy on training
      induced changes in body composition might have been missed with a less precise
      scanning protocol. DXA scans should be undertaken with Best.

PMID- 24458266
TI  - Heightened plasma levels of heme oxygenase-1 and tissue inhibitor of
      metalloproteinase-4 as well as elevated peripheral neutrophil counts are
      associated with TB-diabetes comorbidity.
AB  - BACKGROUND: The increased prevalence of type 2 diabetes mellitus (T2DM) in
      countries endemic for TB poses a serious complication in the clinical management
      of this major infectious disease. Understanding the impact of T2DM on TB and the
      determinants of comorbidity is critical in responding to this growing public
      health problem with better therapeutic approaches. Here, we performed an
      exploratory study assessing a series of biologic parameters that could serve as
      markers of pathogenesis in TB with T2DM. METHODS: Cross-sectional analyses of
      levels of heme oxygenase-1 (HO-1), acute phase proteins, tissue
      metalloproteinases, and tissue inhibitors of metalloproteinase (TIMPs) as well as
      cytokines and chemokines were performed in plasma samples from individuals with
      active pulmonary TB or with coincident TB and T2DM from South India. RESULTS:
      Compared with patients with TB without diabetes, those with coincident T2DM
      exhibited increased Mycobacterium tuberculosis bacillary loads in sputum. Plasma
      levels of HO-1 but not of other acute phase proteins were higher in patients with
      TB and T2DM than in patients without diabetes, independent of bacillary sputum
      loads. HO-1 concentrations also positively correlated with random plasma glucose,
      circulating glycosylated hemoglobin, and low-density lipoprotein levels.
      Moreover, patients with coincident TB and T2DM exhibited increased plasma levels
      of TIMP-4 and elevated peripheral blood neutrophil counts, which, when considered
      together with HO-1, resulted in increased power to discriminate individuals with
      active TB with and without T2DM. CONCLUSIONS: Elevated plasma levels of HO-1 and
      TIMP-4 and peripheral blood neutrophil counts are potential single and combined
      markers of pathogenesis in TB and T2DM.

PMID- 24458268
TI  - Effect of defects on the intrinsic strength and stiffness of graphene.
AB  - It is important from a fundamental standpoint and for practical applications to
      understand how the mechanical properties of graphene are influenced by defects.
      Here we report that the two-dimensional elastic modulus of graphene is maintained
      even at a high density of sp(3)-type defects. Moreover, the breaking strength of
      defective graphene is only ~14% smaller than its pristine counterpart in the
      sp(3)-defect regime. By contrast, we report a significant drop in the mechanical
      properties of graphene in the vacancy-defect regime. We also provide a mapping
      between the Raman spectra of defective graphene and its mechanical properties.
      This provides a simple, yet non-destructive methodology to identify graphene
      samples that are still mechanically functional. By establishing a relationship
      between the type and density of defects and the mechanical properties of
      graphene, this work provides important basic information for the rational design
      of composites and other systems utilizing the high modulus and strength of
      graphene. 

PMID- 24458267
TI  - MTHFR C677T genotype and cardiovascular risk in a general population without
      mandatory folic acid fortification.
AB  - PURPOSE: Meta-analyses have suggested an effect of MTHFR C677T genotype
      (rs1801133), a proxy for blood total homocysteine, on cardiovascular disease
      (CVD) in populations with low population dietary folate. The aim was to examine
      the association and effect modification by serum folate and vitamin B12 levels
      between MTHFR and CVD-related outcomes in a general population with no mandatory
      folic acid fortification policy. METHODS: The study population included 13,748
      adults retrieved from pooling of four population-based studies conducted in
      Denmark. MTHFR genotype, serum folate (measured in approximately 9,356
      individuals), and serum vitamin B12 (9,215 individuals), hypertension, and
      dyslipidemia were measured at baseline, and participants were followed for a mean
      of 10.5-11.7 years in central registries for diagnoses of stroke (623 incidents),
      ischaemic heart disease (IHD) (835 incidents), and all-cause mortality (1,272
      incidents). RESULTS: The MTHFR genotype (TT vs. CC/CT) was not associated with
      hypertension [OR (95% CI) 1.09 (0.95-1.25)], dyslipidemia [OR (95% CI) 0.97 (0.84
      1.11)], stroke [HR (95% CI) 0.92 (0.69-1.23)], and all-cause mortality [HR (95%
      CI) 0.94 (0.77-1.14)], either overall, or in participants with low serum folate
      or B12 status (P values for interactions 0.15-0.94). Individuals with the MTHFR
      TT genotype had a higher risk of IHD (HR (95% CI) 1.38 (1.11-1.71)), but this
      association was not modified by folate status (P value for interaction 0.45).
      CONCLUSIONS: Our results do not support a causal relationship between
      homocysteine and CVD. However, we cannot exclude a direct causal effect of MTHFR
      C677T genotype on IHD.

PMID- 24458269
TI  - Judging a man by the width of his face: the role of facial ratios and dominance
      in mate choice at speed-dating events.
AB  - Previous research has shown that men with higher facial width-to-height ratios
      (fWHRs) have higher testosterone and are more aggressive, more powerful, and more
      financially successful. We tested whether they are also more attractive to women
      in the ecologically valid mating context of speed dating. Men's fWHR was
      positively associated with their perceived dominance, likelihood of being chosen
      for a second date, and attractiveness to women for short-term, but not long-term,
      relationships. Perceived dominance (by itself and through physical
      attractiveness) mediated the relationship between fWHR and attractiveness to
      women for short-term relationships. Furthermore, men's perceptions of their own
      dominance showed patterns of association with mating desirability similar to
      those of fWHR. These results support the idea that fWHR is a physical marker of
      dominance. This is the first study to show that male dominance and higher fWHRs
      are attractive to women for short-term relationships in a controlled and
      interactive situation that could actually lead to mating and dating.

PMID- 24458270
TI  - Racial bias shapes social reinforcement learning.
AB  - Both emotional facial expressions and markers of racial-group belonging are
      ubiquitous signals in social interaction, but little is known about how these
      signals together affect future behavior through learning. To address this issue,
      we investigated how emotional (threatening or friendly) in-group and out-group
      faces reinforced behavior in a reinforcement-learning task. We asked whether
      reinforcement learning would be modulated by intergroup attitudes (i.e., racial
      bias). The results showed that individual differences in racial bias critically
      modulated reinforcement learning. As predicted, racial bias was associated with
      more efficiently learned avoidance of threatening out-group individuals. We used
      computational modeling analysis to quantitatively delimit the underlying
      processes affected by social reinforcement. These analyses showed that racial
      bias modulates the rate at which exposure to threatening out-group individuals is
      transformed into future avoidance behavior. In concert, these results shed new
      light on the learning processes underlying social interaction with racial-in
      group and out-group individuals. 

PMID- 24458271
TI  - TPO signal for stem cell genomic integrity.
AB  - In this issue of Blood, de Laval et al report on a novel mechanism by which
      hematopoietic stem cells (HSCs) harboring DNA damage are rescued by
      thrombopoietin (TPO)-mediated DNA repair.1 It has been recently demonstrated that
      HSCs use the error-prone nonhomologous end-joining (NHEJ) pathway of DNA repair
      to fix DNA breaks. Maintenance of genomic integrity is crucial for HSC function.
      Finding the players involved in HSC DNA repair will provide a better
      understanding of hematopoietic homeostasis, HSC aging, and leukemogenesis.

PMID- 24458272
TI  - Not like a wrecking ball: EBV fine-tunes MYC lymphomagenesis.
AB  - In this issue of Blood, Fish et al uncover how Epstein-Barr virus (EBV) enhances
      MYC-driven B-cell lymphoma by crossing EBV Em-EBV latent membrane protein 2A
      (LMP2A) transgenic mice with immunoglobulin-l (Igl)-MYC transgenic mice.

PMID- 24458273
TI  - Severe congenital neutropenia: new lane for ELANE.
AB  - In this issue of Blood, Tidwell et al1 demonstrate that mutations in the start
      codon (protein synthesis is initiated at the codon ATG) of neutrophil elastase
      (ELANE) result in the production of N-terminally truncated elastase, which
      mislocates to the nucleus and results in severe congenital neutropenia (SCN).

PMID- 24458274
TI  - Core fucosylation and IgG function in NAIT.
AB  - In this issue of Blood, Kapur et al show that maternal human platelet-specific
      antigen 1a (HPA 1a)-specific antibodies causing neonatal alloimmune
      thrombocytopenia (NAIT) possess oligosaccharides that are deficient in "core
      fucose" residues and appear to be more effective than fucosylated antibodies in
      promoting phagocytosis of antibody-coated platelets.

PMID- 24458275
TI  - "Packaging" of fetal hemoglobin in sickle cell anemia.
AB  - In this issue of Blood, Steinberg et al describe the clinical importance of the
      distribution or "packaging" of fetal hemoglobin (HbF) within erythrocytes of
      persons with sickle cell anemia.

PMID- 24458276
TI  - Long noncoding RNAs in erythropoiesis.
AB  - In this issue of Blood, Alvarez-Dominguez et al use a combination of genomics
      technology, bioinformatics, and functional analyses to provide new insights into
      our understanding of the role of long noncoding RNAs (lncRNAs) in
      erythropoiesis.1 This is an initial step forward in our understanding of the many
      roles of lncRNAs in normal and perturbed erythropoiesis. lncRNAs have recently
      emerged as critical, multifunctional regulators of cellular gene expression.

PMID- 24458277
TI  - PAI at breakfast (whether you like it or not).
AB  - In this issue of Blood, Scheer and Shea report that the morning surge of the
      prothrombotic factor plasminogen activator inhibitor-1 (PAI-1) observed in humans
      is driven by an endogenous mechanism (as opposed to behavioral/environmental
      influences).

PMID- 24458278
TI  - Natural killer cells acquire CD73 expression upon exposure to mesenchymal stem
      cells.

PMID- 24458279
TI  - The FIP1L1-PDGFRA fusion gene and the KIT D816V mutation are coexisting in a
      small subset of myeloid/lymphoid neoplasms with eosinophilia.

PMID- 24458280
TI  - Akt is essential to induce NADPH-dependent NETosis and to switch the neutrophil
      death to apoptosis.

PMID- 24458281
TI  - Integrated optical gyroscope using active long-range surface plasmon-polariton
      waveguide resonator.
AB  - Optical gyroscopes with high sensitivity are important rotation sensors for
      inertial navigation systems. Here, we present the concept of integrated resonant
      optical gyroscope constructed by active long-range surface plasmon-polariton
      (LRSPP) waveguide resonator. In this gyroscope, LRSPP waveguide doped gain medium
      is pumped to compensate the propagation loss, which has lower pump noise than
      that of conventional optical waveguide. Peculiar properties of single
      polarization of LRSPP waveguide have been found to significantly reduce the
      polarization error. The metal layer of LRSPP waveguide is electro-optical
      multiplexed for suppression of reciprocal noises. It shows a limited sensitivity
      of ~10(-4) deg/h, and a maximum zero drift which is 4 orders of magnitude lower
      than that constructed by conventional single-mode waveguide.

PMID- 24458283
TI  - Effects of hydroxylamine and silicomolybdate on the decay in delayed light
      emission in the 6-100 MUs range after a single 10 ns flash in pea thylakoids.
AB  - Measurements are reported on MUs delayed light emission, following a single 10 ns
      excitation flash, in Alaska pea thylakoids treated with hydroxylamine (NH2OH) or
      with silicomolybdate. 1. In thylakoids treated with 2 mM NH2OH in the light, or
      in the dark, the quantum yield of delayed light emission is considerably
      enhanced. A 10 MUs lifetime component of delayed light emission is not
      significantly changed, whereas a 50-70 MUs lifetime component is increased. MnCl2
      and diphenylcarbazide are unable to reverse the above effects of NH2OH treatment.
      Thus Mn(2+) and diphenylcarbazide must not donate electrons directly to reaction
      center II but on the oxygen-evolution side of the NH2OH block. 2. When the closed
      form of photosystem II reaction centers (P680Q(-)), where P680 is the reaction
      center chlorophyll and Q is a 'stable' electron acceptor, is generated by
      preillumination of NH2OH-treated thylakoids with diuron present, the MUs delayed
      light emission is inhibited, but a low level residual delayed light emission
      remains. Possible origins of this emission are discussed. It is believed that the
      best explanation for residual DLE is the existence of another acceptor besides Q
      that partakes in charge separation and rapid dissipative recombination when the
      reaction center is in the P680Q(-) state. 3. The quantum yield of delayed light
      emission from 'closed' reaction centers (P680 (+)Q(-)) that have all charge
      stabilization reactions (i.e., flow of electrons to P680 (+) and out of Q(-))
      blocked by NH2OH treatment and addition of diuron is 1.1*10(-3) for components
      measured in a range from 6 to 400 MUs and extrapolated to zero time. 4. The
      addition of silicomolybdate, which accepts electron from Q(-), causes delayed
      light emission in the MUs range to be greatly inhibited. 

PMID- 24458282
TI  - Year in review in Intensive Care Medicine 2013: II. Sedation, invasive and
      noninvasive ventilation, airways, ARDS, ECMO, family satisfaction, end-of-life
      care, organ donation, informed consent, safety, hematological issues in
      critically ill patients.

PMID- 24458284
TI  - Electron transport and chloroplast ultrastructure of a chlorophyll deficient
      mutant of wheat.
AB  - A non-lethal chlorophyll deficient mutation was induced by use of the chemical
      mutagen ethyl methanesulfonate. Chloroplasts from the control and mutant plants
      were found to be very similar ultrastructurally. Thylakoid membrane volume was
      only slightly greater in plastids from the control as compared with plastids from
      the mutant. The chlorophyll content of the mutant was reduced by over 60%. This
      decrease in chlorophyll was not accompanied by a similar decrease in electron
      transport. Uncoupled electron transport rate based on a unit chlorophyll basis
      was nearly twice as great for mutant chloroplasts as for control plastids.
      However, electron transport rate based on a unit membrane volume was similar in
      mutant and control plants. At high irradiance the relative quantum requirement of
      the control and mutant was similar when expressed on membrane volume. 

PMID- 24458285
TI  - Reconstitution of electron transport by cytochrome c-553 in a cell-free system of
      Nostoc muscorum.
AB  - Treatment of spheroplasts of Nostoc museorum with hypotonic buffer results in
      membranes depleted of cytochrome c-553, but still active in photosynthetic and
      respiratory electron transport. These membranes retain full photosystem II
      activity (H2O->DADox). Complete linear electron transport (H2O->NADP(+)),
      however, is decreased as compared with untreated spheroplasts. Addition of basic
      Nostoc cytochrome c-553 to depleted membranes reconstitutes NADP(+) reduction and
      redox reactions of the photosystem I region as well.Using NADPH as electron
      donor, respiration of depleted membranes is also stimulated by adding cytochrome
      c-553, indicative of its function in respiratory electron transport.Cytochrome c
      553 from Bumilleriopsis filiformis, Spirulina platensis (acidic types),
      Phormidium foveolarum (basic type), and mitochondrial horse-heart cytochrome c
      550 are not effective in reconstituting both photosynthetic and respiratory
      electron transport, which points to a specific role of Nostoc cytochrome c-553. 

PMID- 24458286
TI  - A single step separation of PS 1, PS 2 and chlorophyll-antenna particles from
      spinach chloroplasts.
AB  - After solubilization of photosynthetic membranes by digitonin, three main protein
      pigment complexes were isolated by electrophoresis with deoxycholate as
      detergent.The band with the slowest mobility, fraction 1, had PS 1 activity and
      was devoid of PS 2 activity. This fraction was four times enriched in P700 when
      compared with chloroplasts. Fraction 1 had little chl b, a long wavelength
      absorption maximum in the red, a maximum of low temperature emission fluorescence
      at 730nm, and a circular dichroism spectrum characteristic of PS 1 enriched
      fraction.Fraction 2 exhibited a PS 2 activity and no PS 1 activity. It was
      enriched five times in PS 2 reaction centre and had little chl b and carotenoids.
      The absorption maximum was at 674 nm and the low temperature fluorescence
      emission maximum was at 700 nm. Fraction 2 might be useful PS 2 enriched particle
      because of the great stability of this fraction with regard to photochemical
      activity and also rapidity and simplicity of its preparation.Fraction 3, which
      had the fastest migration, was devoid of photochemical activities; It was rich in
      chl b and had the fluorescence and the circular dichroism spectrum characteristic
      of an antenna complex. 

PMID- 24458287
TI  - Protein identification of purified particles isolated from spinach thylakoids by
      deoxycholate electrophoresis.
AB  - Three thylakoid complexes were isolated by deoxycholate preparative
      electrophoresis. The protein composition of each fraction was analyzed by SDS
      analytical electrophoresis. No protein of the PS 1 enriched fraction (fraction 1)
      was found in the PS 2 enriched fraction (fraction 2) and inversely. The antenna
      complex (fraction 3) did not have any contamination by proteins of fraction 1 or
      fraction 2. Fraction 1 was mainly composed of the CP1, the reaction center
      complex of the PS1, and by low molecular weight proteins, previously found in
      other PS 1 preparations. Tentative assignments of these proteins are presented;
      among them are iron sulfur proteins. After analytical SDS electrophoresis of
      fraction 2, the reaction center complex was dissociated. Nevertheless three
      proteins of 50 kD, 42 kD and 35 kD were assigned to this complex. Fraction 2
      contained also the three cytochromes of the thylakoid membranes: cyt f, cyt b6,
      cyt b559. Fraction 3 was exclusively composed of one protein pigment complex,
      CP2. 

PMID- 24458288
TI  - The stability of electron transport in in vitro chloroplast membranes.
AB  - The stability and stabilization of the electron transport system of chloroplast
      membranes under physiological conditions of temperature and illumination were
      studied in relation to two separate and often competing mechanisms of decay.
      Photochemical inactivation (photoinhibition) of the electron transport system of
      ageing spinach chloroplasts was not normally found to limit stability even at
      saturating light intensities. Only when the membranes were protected from dark
      (fatty acid) inhibition did photoinhibition limit stability.Electron transport
      could be partially protected from dark inhibition by the addition of high
      concentrations of recrystallized (i.e. fatty acid free) bovine serum albumin,
      ovalbumin, polyethyleneimine cellulose, Biomesh SM2 beads or with Ficoll 400.
      Some improvement in stability was achieved with N,N, dimethylphenethylamine but
      other esterase and phospholipase inhibitors were ineffective in preventing
      thermal inactivation.Photoinhibition was apparently delayed by phenazine
      methosulphate under certain conditions but was unaffected either by artificial
      scavengers of reactive oxygen species (butylated hydroxytoluene), and 1,4
      diazobycyclo (2, 2, 2 octane) or by natural scavengers which constitute part of
      the in vivo protective mechanism (alpha-tocopherol, beta-carotene, SOD, catalase
      and glutathione) or by anaerobic incubation. Photoinhibition may therefore be by
      a separate mechanism which does not initially involve free radical damage. 

PMID- 24458289
TI  - Excitation energy transfer between beta-carotene and chlorophyll-a in various
      systems.
AB  - The excitation energy transfer from beta-carotene to chlorophyll-a in several
      seminatural systems such as liposomes, lipid layers and PSI complex has been
      studied at room and liquid nitrogen temperature. Only in a case of PSI complex an
      efficient energy transfer (about 30%) from beta-carotene to chlorophyll-a has
      been observed. The results of energy transfer were discussed on the ground of
      Dexter's mechanism by taking into account the recently discovered energy level
      ((1)Ag) of beta-carotene. 

PMID- 24458290
TI  - Photosynthetic functions and thylakoid membrane polypeptide composition in light
      sensitive mutants of Chlamydomonas reinhardii.
AB  - In this paper we compared the pigment composition, photochemical activity,
      chloroplast ultrastructure, thylakoid membrane polypeptide composition and
      ribosomal content of wild-type and seven light-sensitive mutants of Chlamydomonas
      reinhardii.All the mutants had low chlorophyll and carotenoid content compared to
      wild-type. Mutants lts-30 and lts-135 were also characterized by a complete
      absence of visible carotenoids, while mutant lts-19 was fully deficient in
      chlorophylls.In most mutants, the chloroplast fragment could not carry out any
      DCIP photoreduction and O2 evolution was also blocked. The PSI/P700/activity was
      decreased in most cases.The mutant strains contained mostly single lamellae in
      their plastids, that is the stacking capacity of the thylakoid membranes was very
      decreased or fully absent. In most cases the number of lamellae was also very
      low.The relative amounts of 70 S ribosomes were decreased in all of the mutants.
      The thylakoid membranes showed anomalies in the region of 24 000-30 000 dalton
      polypeptides. The common characteristic for them was the relatively higher amount
      of the 30 000 dalton polypeptide and considerably decreased level of the 27 000
      and 24 000 dalton polypeptides relative to the wild-type. These polypeptides were
      probably constituents of the chlorophyll-protein complex II which has been
      suggested to be the light harvesting pigment complex for PSII. The polypeptide of
      30 000 daltons is the precursor for the LHCP apoprotein (24 000 dalton protein).
      It may be that the lighstimulated conversion of this precursor into LHCP
      apoprotein was blocked in our pigment-deficient mutants. 

PMID- 24458291
TI  - Neuropsychological performance is positively associated with plasma albumin in
      healthy adults.
AB  - BACKGROUND: Albumin serves a range of physiological functions that are vital to
      overall brain and cognitive health. Indeed, associations between cognitive
      performance and albumin have been demonstrated in individuals with chronic liver
      or kidney disease and in patients with a high urinary excretion of albumin.
      However, an association of plasma albumin with cognitive performance has not been
      reported in otherwise healthy participants with clinically acceptable plasma
      albumin concentrations. METHOD: This study utilized a wide-ranging
      neuropsychological test battery to investigate the relationship between cognitive
      performance and plasma albumin homeostasis in 222 healthy participants (143
      females) between the ages of 43 and 84 years (mean 65 years). RESULTS: Albumin
      both with and without the covariates of age, sex and acute-phase proteins was
      positively associated with enhanced performance on a range of neuropsychological
      domains including perceptual speed, Stroop and verbal ability. Albumin manifested
      generally positive but less robust associations with secondary and primary
      memory. CONCLUSION: The results indicate that there is a positive association
      between albumin and cognitive performance in physiologically healthy participants
      free of chronic renal or liver disease.

PMID- 24458292
TI  - The fabrication, characterisation and electrochemical investigation of screen
      printed graphene electrodes.
AB  - We report the fabrication, characterisation (SEM, Raman spectroscopy, XPS and
      ATR) and electrochemical implementation of novel screen-printed graphene
      electrodes. Electrochemical characterisation of the fabricated graphene
      electrodes is undertaken using an array of electroactive redox probes and
      biologically relevant analytes, namely: potassium ferrocyanide(II), hexaammine
      ruthenium(III) chloride, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), beta
      nicotinamide adenine dinucleotide (NADH), L-ascorbic acid (AA), uric acid (UA)
      and dopamine hydrochloride (DA). The electroanalytical capabilities of the
      fabricated electrodes are also considered towards the sensing of AA and DA. The
      electrochemical and (electro)analytical performances of the fabricated screen
      printed graphene electrodes are considered with respect to the relative surface
      morphologies and material compositions (elucidated via SEM, Raman, XPS and ATR
      spectroscopy), the density of electronic states (% global coverage of edge-plane
      like sites/defects) and the specific fabrication conditions utilised. Comparisons
      are made between two screen-printed graphene electrodes and alternative graphite
      based screen-printed electrodes. The graphene electrodes are fabricated utilising
      two different commercially prepared 'graphene' inks, which have long screen ink
      lifetimes (>3 hours), thus this is the first report of a true mass-reproducible
      screen-printable graphene ink. Through employment of appropriate
      controls/comparisons we are able to report a critical assessment of these screen
      printed graphene electrodes. This work is of high importance and demonstrates a
      proof-of-concept approach to screen-printed graphene electrodes that are highly
      reproducible, paving the way for mass-producible graphene sensing platforms in
      the future.

PMID- 24458293
TI  - Three-dimensional transesophageal echocardiography of atrial septal defect device
      closure.
AB  - Most secundum atrial septal defects (ASD) are amenable to device closure. Three-
      dimensional transesophageal echocardiography (3DTEE) can be used to obtain an en
      face view of the ASD and important surrounding structures which provides for
      analysis of the type, size, shape, orientation, number and position of orifices,
      ASD rims and important surrounding structures in a single live 3D echo view.
      Also, 3DTEE is ideal for monitoring the position and configuration of devices and
      delivery hardware using live real -time imaging techniques. In this chapter we
      will describe and illustrate the methods to obtain and optimize 3DTEE en face
      views of the ASD during device closure using 3D zoom, live 3D and 3D full volume
      plus iCrop modalities. The respective 3D TEE modalities, imaging protocols,
      advantages and limitations will be discussed. Because it is useful, accurate and
      fairly simple to use, we have adopted 3D TEE for routine clinical use during ASD
      device closure. 

PMID- 24458294
TI  - Breast ulceration in a teenager.

PMID- 24458295
TI  - Some characteristics of nitrate reductase induction in Lemna minor L.
AB  - Low levels of nitrate reductase can be detected in plants of Lemna minor grown on
      some organic nitrogen sources. Nitrogen-starvation does not lead to a
      derepression of nitrate reductase activity. Nitrate ions are necessary for the
      development of maximum enzyme activity and the maintenance of high enzyme levels.
      Nitrogen-starvation of ammonia-grown plants increases the subsequent rate of
      nitrate-mediated induction. It is suggested that ammonium ions, either directly
      or indirectly modulate the rate of nitrate reductase induction. The pattern of
      control regulating nitrate reductase levels in Lemna is contrasted with that in
      some species of algae. 

PMID- 24458296
TI  - [Control of aerobic metabolism in starved yeast cells supplied with glucose and
      ammonia].
AB  - When glucose is added to starved yeast cells under strictly aerobic conditions
      ([O2]>90% air saturation) the concentrations of G-6-P, F-6-P, FDP, pyruvate,
      malate and alpha-ketoglutarate rise, whereas those of PEP and PGA fall to a low
      level. This indicates that PK is activated and either GAPDH or PGK becomes rate
      limiting. Exogenous citrate is metabolized only after feeding. The level of
      pyruvate, alpha-ketoglutarate and malate accumulated is lower if ammonia was
      added to the medium, which indicates the onset of amino acid synthesis. The
      concentrations of adenosine and uridine nucleotides are diminished if ammonia is
      present in addition to glucose. Actinomycin prevents the decrease in adenosine
      nucleotide concentrations.The accumulation of FDP and pyruvate after glucose
      addition is more pronounced in the presence of ammonia. This, together with
      changing rates of ethanol accumulation, indicates that PDC is a limiting factor
      during starvation and becomes activated very slowly, especially in the presence
      of ammonia. 

PMID- 24458297
TI  - Endogenous rhythmicity and energy transduction : IV. Rhythmic control of enzymes
      involved in the tricarboxylic-acid cycle and the oxidative pentose-phosphate
      pathway in Chenopodium rubrum L.
AB  - 1. All enzymes tested: malate dehydrogenase (MDH), glutamate dehydrogenase (GDH),
      glucose-6-phosphate dehydrogenase (G-6-PDH), and 6-phosphogluconate dehydrogenase
      (6-P-GDH)_behaved rhythmically during a period of continuous white light
      interrupted by darkness. All showed approximately the same frequency of 12-15 h.
      2. The enzymes of the tricarboxylic-acid cycle (MDH and GDH) are in phase with
      each other but are out of phase with those of the oxidative pentose-phosphate
      pathway (G-6-PDH and 6-P-GDH) which are in turn in phase with each other. 3. GDH
      appears to be activated by the addition of Hoagland's solution which leads to an
      overt rhythm 24 h prior to darkness. The rhythms of MDH, G-6-PDH and 6-P-GDH
      cannot be demonstrated prior to the onset of darkness due to an inhibition of the
      MDH and pentose-phosphate cycle enzymes by light. 4. The control of the frequency
      and phase of these rhythms are discussed in relation to a positive correlation of
      the rhythms in enzyme activity presented here and the rhythms of the pyridine
      nucleotides presented elsewhere. 

PMID- 24458298
TI  - Activation and de novo synthesis of ribonuclease following mechanical damage to
      leaves of Solanum tuberosum L.
AB  - The pattern of changes in RNase activity in damaged potato leaves incubated in
      the presence of [(14)C]leucine followed closely that of leaves incubated in the
      absence of the radioisotope, but the levels of activity during time course
      experiments were consistently lower. Contributions of other nucleolytic enzymes
      to the increased capacity of damaged leaves to hydrolyse RNA were slight.Two
      peaks of RNase activity were isolated from leaves that had been damaged for 24 h.
      One of these peaks represented a form of the enzyme that occurred in undamaged
      leaves and which increased markedly in activity on damage. The second peak
      represented a novel form of the enzyme which still possessed appreciable
      radioactivity after further extensive purification. It is suggested that a
      component of this peak was due to de novo synthesis of enzyme. Several additional
      new peaks of RNase activity were resolved from homogenates of leaves which had
      been damaged for 48 h. None of these peaks contained a significant amount of
      radioactivity when final purification was attained. It was concluded that
      although some de novo synthesis of RNase may occur during the first 24 h
      following mechanical damage the majority of increased enzyme activity up to that
      point and thereafter is due to activation of pre-formed enzyme. 

PMID- 24458299
TI  - The role of the cotyledons in the photocontrol of hypocotyl extension in Cucumis
      sativus L.
AB  - Extension growth of the hypocotyl of de-etiolated cucumber seedlings is inhibited
      by blue and red light, the latter operating through the phytochrome system. The
      major part of the inhibition due to red light is mediated through the cotyledons
      which transmit the effect to the hypocotyl. On the other hand, blue light acts
      directly upon the hypocotyl, the cotyledons apparently not being involved. Thus,
      there is a morphological separation of spectral sensitivity. The role of the
      cotyledons is evident only in de-etiolated seedlings. Etiolated plants also
      differ in being sensitive to prolonged far-red light whose effect becomes less
      apparent as seedlings age. De-etiolation seems to abolish sensitivity to far-red.

PMID- 24458300
TI  - Differential properties of phosphoenolpyruvate carboxylase from etiolated and
      green sugar cane.
AB  - Phosphoenolpyruvate (PEP) carboxylase has been isolated from etiolated and light
      grown sugar cane, and a comparison made of the physical and kinetic
      characteristics of the enzymes. Differences were found in the DEAE-cellulose
      elution profiles, in saturation kinetics with PEP as variable substrate and with
      Mg(2+) as variable cofactor, in sensitivities to NaCl as an inhibitor and glucose
      6-phosphate as an activator. The etiolated tissue form consistently showed
      properties resembling more closely PEP carboxylase from a C3 plant than from a C4
      plant, with K m PEP and K0.5 Mg values lower than the green tissue form, and
      markedly less sensitivity to NaCl and glucose-6-phosphate. 

PMID- 24458301
TI  - [Relationship between anthocyanin synthesis and activity of phenylalanine ammonia
      lyase (PAL) in callus cells of Daucus carota].
AB  - Two celllines from Daucus carota callus were tested for phenylalanine ammonia
      lyase activity. The white callus (DCw) has only 15% of the enzyme activity of the
      blue callus (DCb). The enzyme activity reaches a maximum value after a
      cultivation period of 21 days, whereas the maximum in anthocyanin content is
      reached after 28 days. We can demonstrate here a good correlation between one of
      the enzymes and the end product of the anthocyanin biosynthesis.The crude extract
      from DCw cells has no inhibitory effect on the enzyme from DCb-cells. Gibberellic
      acid A3, a component of the culture medium for DCw cells, does not act as an
      inhibitor on the partially purified enzyme. The procedure of purification and the
      characteristics of phenylalanine ammonia-lyase from the callus of Daucus carota
      are described. 

PMID- 24458302
TI  - [On the activity of synthetase and phosphorylase in maize leaves at different
      starch levels].
AB  - The activities of phosphorylase and synthetase in the bundle sheath cells of
      maize leaves were investigated in plants that as a result of different light-dark
      treatments contained various amounts of starch. The material coming from the dark
      (67 h) had almost no starch and scarcely any synthetase activity if starch
      granules were not added to the assay mixture as a primer. In the presence of this
      primer a poor synthetase activity could be detected. After 2 h in the light the
      leaves produced a small amount of starch and the synthetase activity increased.
      When starch granules were included in the test the synthetase activity was
      increased 3.5-fold. This value was 1.5-fold higher than the corresponding one in
      the dark. Plants that were in the light for 28 h contained fair amounts of starch
      and the synthetase activity was independent of the addition of primer. The values
      were 3 fold higher than those found in plants in the dark. A further increase in
      the synthetase activity and decrease in starch content were brought about by a
      dark period of 2 h following the illumination of 28 h.The total activity of
      phosphorylase remained high and almost constant in all these materials and did
      not require the addition of primer to attain a maximal value. In the material
      coming from the dark, the product produced by the activity of phosphorylase in
      absence of added primer could serve as a good primer for the synthetase. From the
      comparison of the amounts of starch produced in vivo under different conditions
      and the enzymic activities found we conclude that the first steps of starch
      synthesis are carried out by phosphorylase and that further on both enzymes
      participate in the process. 

PMID- 24458303
TI  - Polysaccharide sulphation in Laminaria.
AB  - E. M. autoradiography using (35)SO4 (2-) has shown the Golgi complex to be the
      site of polysaccharide sulphation in the brown seaweed Laminaria. 

PMID- 24458304
TI  - [Carbonic anhydrase levels and enzymes of the glycolate pathway in the blue-green
      alga Anacystic nidulans].
AB  - The blue-green alga Anacystis nidulans (strain L 1402-1) was grown in air (0.03
      vol. % CO2) and in 3.0 vol. % CO2 at +35 degrees  C. Levels of carbonic anhydrase
      were 3-fold higher in air-grown cells than in CO2-grown algae. CO2 content during
      growth has no effect on activity of RuDP carboxylase. Activities of PEP
      carboxylase, malic enzyme and catalase were higher in CO2-grown Anacystis cells.
      In air-grown cells higher activities of malate dehydrogenase, glycolate
      dehydrogenase, serine-pyruvate aminotransferase and aspartate-alpha-ketoglutarate
      aminotransferase were found. Levels of these enzymes are relatively low compared
      to those in green algae and higher plants. 

PMID- 24458305
TI  - Sensitive determination of reactive oxygen species in cigarette smoke using
      microchip electrophoresis-localized surface plasmon resonance enhanced
      fluorescence detection.
AB  - A sensitive approach to the determination of reactive oxygen species (ROS) in
      puffs of cigarette smoke (CS) has been developed. The experimental system
      consists of a microfluidic chip electrophoresis and a laser induced fluorescence
      (LIF) device enhanced by localized surface plasmon resonance. Core-shell Ag@SiO2
      nanoparticles were prepared and then immobilized on the surface of the
      microchannel to increase the fluorescence intensity based on localized surface
      plasmon resonance-enhanced fluorescence (LSPREF) effect. The ROS in puffs of CS
      were trapped via the oxidation of 2',7'-dichlorodihydrofluorescein (DCHF) that
      had been loaded on polyacrylonitrile (PAN) nanofibers in a micro-column.
      Determination of ROS was based on the amount of 2',7'-dichlorofluorescein (DCF),
      which is the sole product from DCHF oxidation. With the optimization of the
      trapping efficiency, we detected about 8.0 pmol of ROS per puff in the mainstream
      CS. This microchip electrophoresis-SPREF system enables sensitive quantitation of
      ROS in CS with low consumption of reagent, material, and analysis time. 

PMID- 24458306
TI  - Spatial and seasonal distribution of 17 endocrine disruptor compounds in an urban
      estuary (Mondego River, Portugal): evaluation of the estrogenic load of the area.
AB  - The Mondego River estuary demonstrates signs of pollution, but the levels of
      endocrine disrupting compounds (EDCs), such as the natural (17beta-estradiol and
      estrone) and pharmaceutical (17alpha-ethynylestradiol) estrogens, xenoestrogenic
      industrial pollutants (4-octylphenol, 4-nonylphenol, and their mono- and
      diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A,
      daidzein, and genistein), and sitosterol were either poorly or never measured in
      this area. Thus, to conclude about the influx of EDCs in this estuary, water
      samples were taken every 2 months, during 1 year (2010) in low tide, at eight
      sites distributed along the estuary. Water samples (1 L) were preconcentrated in
      the Oasis HLB cartridges and cleaned in silica cartridges before their analysis
      by GC-MS. In summer, potentially hazardous amounts of estrogens (~ 26 ng L(-1)),
      alkylphenols (~ 11.5 MUg L(-1)), alkylphenolethoxylates (~ 13 MUg L(-1)), and
      phytoestrogens (~ 5.6 MUg L(-1)) were measured. These data suggest that changes
      in the hydrodynamics of the estuary coupled with the increase of water
      temperatures interfere with the amount of EDCs in the water. Complementary
      physicochemical parameters also point to high levels of anthropogenic pollution
      in this area. Globally, the estrogenic load, expressed in ethynylestradiol
      equivalents, attained 71.8 ng L(-1) demonstrating that, all together, the
      measured EDCs pose important health risks for both biota and humans.

PMID- 24458307
TI  - Growth inhibition and differences in protein profiles in azadirachtin-treated
      Drosophila melanogaster larvae.
AB  - Azadirachtin A is a very effective biopesticide widely used in insect pest
      control. It has strong antifeeding and growth inhibitory activity against most
      insects, however, its mode of action is still unclear. Proteomic experiments
      using 2DE indicate significant effects of Azadirachtin A on the amount of
      proteins related to growth inhibition in Drosophila melanogaster larvae. Twenty
      one spots with different intensity in azadirachtin-treated larvae were
      identified. These proteins are involved in cytoskeletal organization,
      transcription and translation, hormonal regulation, and energy metabolism.
      Protein network analysis reveals heat shock protein 23 to be a potential target
      of azadirachtin. These results provide new insights into understanding the
      mechanism of growth inhibition in insects in response to azadirachtin.

PMID- 24458308
TI  - Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the
      balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice
      with collagen-induced arthritis.
AB  - OBJECTIVE: To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature
      dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory
      and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis
      (CIA). METHODS: BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and
      were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine
      2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)
      beta1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by
      immunization with type II collagen. CIA mice were injected intravenously with BM
      CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM
      CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint
      histopathology, body weight, thymus index, thymocytes proliferation, IL-1beta,
      tumor necrosis factor (TNF)-alpha, IL-17, IL-10 and TGF-beta1 levels. RESULTS: BM
      CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR
      2, IDO, IL-10 and TGF-beta1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice
      significantly reduced the arthritis index and pathological scores of joints,
      recovered the weight, decreased the thymus index and inhibited thymocyte
      proliferation. Levels of IL-1beta, TNF-alpha and IL-17 were decreased in BM
      CD11b(+)F4/80(+)iDC-treated mice. CONCLUSIONS: BM CD11b(+)F4/80(+)iDC can be
      induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment
      can ameliorate the development and severity of CIA by regulating the balance
      between pro-inflammatory cytokines and anti-inflammatory cytokines.

PMID- 24458309
TI  - Balanced and unbalanced solutions modulate the release of Matrix
      Metalloproteinase-9 (MMP-9) from neutrophils in response to inflammatory stimuli:
      an in vitro study.
AB  - OBJECTIVES AND DESIGN: We investigated the effect of balanced (BS) and unbalanced
      (UBS) solutions in the absence or presence of hydroxyethyl starch (HES) on
      neutrophil functionality, evaluating the release of matrix metalloproteinase
      (MMP)-9, myeloperoxidase (MPO), and MMP-8. MATERIALS AND METHODS: Neutrophils
      were isolated by gradient centrifugation and dextran sedimentation and incubated
      in BS or UBS without or with HES, in the absence or presence of Interleukin-8 (IL
      8) or Lipopolysaccharide (LPS). MMP-9, MPO, and MMP-8 were assayed by
      commercially available ELISA kits. RESULTS: There was not any influence of volume
      replacement solutions on the release of the enzymes from resting neutrophils.
      After IL-8 stimulation, the release of MMP-9 was higher in BS than in UBS or RPMI
      1640, whereas HES enhanced its release regardless of the composition. After LPS
      stimulation, the release of MMP-9 was higher in both UBS and BS than RPMI-1640,
      but HES brought its release back to physiological conditions. No difference was
      found in the release of MPO and MMP-8 after stimulation with IL-8 or LPS.
      CONCLUSION: Volume replacement solutions might have an impact on the release of
      MMP-9 depending on the inflammatory milieu, suggesting that the use of balanced
      or unbalanced solutions is not a neutral choice.

PMID- 24458310
TI  - A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a
      Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer.
AB  - Bladder cancer is one of the most common cancers and, together with prostate
      carcinoma, accounts for the majority of the malignancies of the genitourinary
      tract. Since prognosis ameliorates with early detection, it will be beneficial to
      have a repertoire of diagnostic markers that could complement the current
      diagnosis protocols. Recently, cell-secreted extracellular vesicles have received
      great interest as a source of low invasive disease biomarkers because they are
      found in many body fluids, including urine. The current work describes a pilot
      study to generate an array-based catalogue of mRNA associated to urinary
      vesicles, and also a comparison with samples obtained from bladder cancer
      patients. After an analysis of presence/absence of transcripts in bladder cancer
      EVs, a list of genes was selected for further validation using PCR technique. We
      found four genes differentially expressed in cancer samples. LASS2 and GALNT1
      were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non
      cancer urinary vesicles. Previous studies have pointed to the involvement of
      those genes in tumour progression and metastasis. 

PMID- 24458311
TI  - A comparison of health-related quality of life in idiopathic pulmonary fibrosis
      and chronic hypersensitivity pneumonitis.
AB  - BACKGROUND: Patients with interstitial lung disease (ILD) have poor health
      related quality of life (HRQL). However, whether HRQL differs among different
      subtypes of ILD is unclear. The aim of this study was to determine whether HRQL
      was different among patients with idiopathic pulmonary fibrosis (IPF) and chronic
      hypersensitivity pneumonitis (CHP). METHODS: We identified patients from an
      ongoing longitudinal cohort of patients with ILD. HRQL was assessed using the
      Short Form (SF)-36 medical outcomes form (version 2.0). Regression analysis was
      used to determine the association between clinical covariates and HRQL, primarily
      the physical component summary (PCS) and mental component summary (MCS) score. A
      multivariate regression model was created to identify potential covariates that
      could help explain the association between the ILD subtype and HRQL. RESULTS:
      Patients with IPF (n = 102) were older, more likely to be men, and more likely to
      have smoked. Pulmonary function was similar between the groups. The patients with
      CHP (n = 69) had worse HRQL across all eight domains of the SF-36, as well as the
      PCS and MCS, compared with patients with IPF (P < .01-.09). This pattern remained
      after controlling for age and pulmonary function (P < .01-.02). Covariates
      explaining part of the relationship between disease subtype and PCS score
      included severity of dyspnea (P < .01) and fatigue (P < .01). Covariates
      explaining part of the relationship between disease subtype and MCS score
      included severity of dyspnea (P < .01), female sex (P = .02), and fatigue (P =
      .02). CONCLUSIONS: HRQL is worse in CHP compared with IPF. HRQL differences
      between ILD subtypes are explained in part by differences in sex, dyspnea, and
      fatigue.

PMID- 24458312
TI  - A simple strategy to transform health, all over the place.

PMID- 24458314
TI  - The adoption of social media and mobile health technologies for emergency
      preparedness by local health departments: a joint perspective from NACCHO and the
      UPMC center for health security.

PMID- 24458313
TI  - Reassessing provider reporting in the age of electronic surveillance.
AB  - CONTEXT: In 2000, the Centers for Disease Control and Prevention began funding
      health departments to implement integrated electronic systems for disease
      surveillance. OBJECTIVE: Determine the impact of discontinuing provider reporting
      for chronic hepatitis B and C, hepatitis A, and select enteric diseases. DESIGN:
      Laboratory and provider surveillance reports of chronic hepatitis B and C and
      enteric infections (Shiga toxin-producing Escherichia coli, Campylobacter,
      Listeria, noncholera Vibrio [eg, Vibrio parahaemolyticus], Salmonella, Shigella,
      and hepatitis A) diagnosed on January 1, 2007 to December 31, 2010 were compared
      for completeness and timeliness. Number of cases submitted by laboratories,
      providers, or both were assessed. RESULTS: From 2007 to 2010, the proportion of
      cases reported only by providers for enteric disease infections differed by
      disease, ranging from 4% (Shiga toxin-producing E coli) to 20% (noncholera
      Vibrio). For chronic hepatitis C, less than 1% of cases were reported by
      providers only. The number of complete laboratory reports increased over the time
      period from 80% to 95% for chronic hepatitis and 92% to 94% for enteric
      infections. Laboratory reports had higher completion for date of birth, sex, and
      zip codes. Provider reports had less than 60% completion for race/ethnicity
      versus 20% for laboratories. Laboratories were faster than providers at reporting
      chronic hepatitis B (median 4 vs 21 days), chronic hepatitis C (4 vs 18 days),
      Campylobacter (6 vs 10 days), noncholera Vibrio (11 vs 12 days), Salmonella (6 vs
      7 days), Shigella (6 vs 13 days), and hepatitis A (3 vs 8 days); providers were
      faster than laboratories at reporting Shiga toxin-producing E coli (4 vs 7 days)
      and Listeria (5 vs 6 days). CONCLUSIONS: Laboratories reported more cases and
      their reports were timelier and more complete for all categories except
      race/ethnicity for chronic hepatitis, Campylobacter, noncholera Vibrio,
      Salmonella, Shigella, and hepatitis A. For chronic hepatitis, provider reporting
      could be eliminated in New York City with no adverse effects on disease
      surveillance. For enteric infections, more work is needed before discontinuing
      provider reporting.

PMID- 24458315
TI  - Million hearts, three levers.

PMID- 24458317
TI  - Energy interactions in amyloid-like fibrils from NNQQNY.
AB  - We use large-scale MP2 calculations to analyze the interactions appearing in
      amyloid fibers, which are difficult to determine experimentally. To this end,
      dimers and trimers of the hexapeptide NNQQNY from the yeast prion-like protein
      Sup35 were considered as model systems. We studied the energy interactions
      present in the three levels of organization in which the formation of amyloid
      fibrils is structured. The structural changes in the hydrogen bonds were studied
      too. It was found that the most energetic process is the formation of the beta
      sheet, which is equally due to both hydrogen bonds and van der Waals
      interactions. The aromatic rings help stabilize these aggregates through stacking
      of the aromatic rings of tyrosine, the stability produced by the aromatics
      residues increasing with their aromaticity. The formation of the basic unit of
      the assembled proto-fiber, the steric zipper, is less energetic and is associated
      to both dispersion forces and hydrogen bonds. The interactions between pair of
      beta-sheets across the peptide-to-peptide contact through the tyrosine rings are
      cooperative and due to dispersion effects. Moreover, the strength of this
      interaction can rationalize the variation of mobility of the aromatic ring in the
      tyrosine units found in solid NMR experiments. 

PMID- 24458316
TI  - Effect of nicotine replacement therapy on quitting by young adults in a trial
      comparing cessation services.
AB  - CONTEXT: Young adult smokers have the highest smoking prevalence among all US age
      groups but are least likely to use evidence-based cessation counseling or
      medication to quit. OBJECTIVE: Use and effectiveness of nicotine patch were
      explored in a randomized trial evaluating smoking cessation interventions with
      this population. PARTICIPANTS: Smokers aged 18 to 30 (n = 3094) were recruited
      through online and off-line methods and from telephone quit lines and analyzed.
      DESIGN: Smokers were enrolled in a pretest-posttest trial, and randomized to 1 of
      3 cessation services. SETTING: Trial delivering counseling services by self-help
      booklet, telephone quit lines, or online expert system in the 48 continental
      United States. INTERVENTION: Smokers could request a free 2-week course of
      nicotine replacement therapy (NRT) patches from the project. MAIN OUTCOME
      MEASURE: Follow-up surveys at 12 and 26 weeks assessed smoking abstinence, use of
      NRT, counseling, and other cessation medications, and smoking-related variables.
      RESULTS: Overall, 69.0% of smokers reported using NRT (M = 3.2 weeks) at 12 weeks
      and 74.8% (M = 3.3 weeks) at 26 weeks. More smokers who were sent the free
      nicotine patches (n = 1695; 54.8%) reported using NRT than those who did not
      receive them (12 weeks: 84.3% vs 41.9%, P < .001; 26 weeks: 87.6% vs 51.1%, P <
      .001). The use of NRT was associated with greater smoking abstinence at 12 weeks
      (P < .001) and 26 weeks (P < .05), especially if used for more than 2 weeks (P <
      .001). Smokers assigned to a self-help booklet or cessation Web site and heavier
      smokers were most likely to use NRT (P < .05), whereas those reporting marijuana
      use and binge drinking used NRT less (P < .05). CONCLUSIONS: Many young adults
      were willing to try NRT, and it appeared to help them quit in the context of
      community-based cessation services. Strategies should be developed to make NRT
      available to this age group and support them in using it to prevent lifelong
      smoking.

PMID- 24458319
TI  - Antibodies to N-methyl-D-aspartate and other synaptic receptors in
      choreoathetosis and relapsing symptoms post-herpes virus encephalitis.

PMID- 24458320
TI  - Development of a prediction formula of Parkinson disease severity by optical
      coherence tomography.
AB  - The aims of this study were to assess the peripapillary retinal nerve fiber layer
      (RNFL) thickness in patients with Parkinson's disease (PD), to determine its
      correlation with disease severity, and to define a simple biomarker for
      predicting clinical severity. One hundred two eyes from 52 patients affected by
      PD were compared with 97 eyes from 50 age-comparable controls. In all patients,
      peripapillary RNFL thickness was measured by optical coherence tomography (OCT).
      We used the Unified Parkinson's Disease Rating Scale (UPDRS) total score and
      measured responses in the on medication state. Eyes from patients with PD had a
      statistically significant decrease in average peripapillary RNFL thickness
      compared with control eyes (P < 0.001). This reduction was observed in every
      quadrant (inferior, superior, nasal [P < 0.001], and temporal [P = 0.017]) in
      patients with PD. Furthermore, a strong inverse correlation was found between the
      PD severity measured according to the UPDRS score and the average peripapillary
      RNFL thickness (r = -0.615; P < 0.001) and PD duration (r = -0.303; P = 0.002).
      From these results, we defined a regression equation that predicts the UPDRS
      score from the above-mentioned variables: UPDRS = 81.6 + 29.6 * log PD duration
      (years) - 0.6 * RFNL thickness (MUm). We observed that, as the evolution and
      severity of PD progress, the peripapillary RNFL layer thickness, as evaluated by
      OCT, gradually diminishes. These results suggest that the average peripapillary
      RNFL thickness measured by OCT might be useful as a biomarker to detect the early
      onset and progression of PD.

PMID- 24458321
TI  - Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia
      caused by GOSR2 mutation.
AB  - BACKGROUND: Ramsay Hunt syndrome (progressive myoclonus ataxia) is a descriptive
      diagnosis characterized by myoclonus, ataxia, and infrequent seizures. Often the
      etiology cannot be determined. Recently, a mutation in the GOSR2 gene (c.430G>T,
      p.Gly144Trp) was reported in 6 patients with childhood-onset progressive ataxia
      and myoclonus. METHODS: We evaluated 5 patients with cortical myoclonus, ataxia,
      and areflexia. RESULTS: All 5 patients had the same homozygous mutation in GOSR2.
      Here we present their clinical and neurophysiological data. Our patients (aged 7
      26 years) all originated from the northern Netherlands and showed a remarkably
      homogeneous phenotype. Myoclonus and ataxia were relentlessly progressive over
      the years. Electromyography revealed signs of sensory neuronopathy or anterior
      horn cell involvement, or both, in all patients with absent reflexes.
      CONCLUSIONS: Based on the presented phenotype, we would advise movement disorder
      specialists to consider mutation analysis of GOSR2 in patients with Ramsay Hunt
      syndrome, especially when they also have areflexia.

PMID- 24458322
TI  - Evaluation of a diffusion charger for measuring aerosols in a workplace.
AB  - The model DC2000CE diffusion charger from EcoChem Analytics (League City, TX,
      USA) has the potential to be of considerable use to measure airborne surface area
      concentrations of nanoparticles in the workplace. The detection efficiency of the
      DC2000CE to reference instruments was determined with monodispersed spherical
      particles from 54 to 565.7 nm. Surface area concentrations measured by a DC2000CE
      were then compared to measured and detection efficiency adjusted reference
      surface area concentrations for polydispersed aerosols (propylene torch exhaust,
      incense, diesel exhaust, and Arizona road dust) over a range of particle sizes
      that may be encountered in a workplace. The ratio of surface area concentrations
      measured by the DC2000CE to that measured with the reference instruments for
      unimodal and multimodal aerosols ranged from 0.02 to 0.52. The ratios for
      detection efficiency adjusted unimodal and multimodal surface area concentrations
      were closer to unity (0.93-1.19) for aerosols where the majority of the surface
      area was within the size range of particles used to create the correction. A
      detection efficiency that includes the entire size range of the DC2000CE is
      needed before a calibration correction for the DC2000CE can be created. For
      diesel exhaust, the DC2000CE retained a linear response compared to reference
      instruments up to 2500 mm(2) m(-3), which was greater than the maximum range
      stated by the manufacturer (1000 mm(2) m(-3)). Physical limitations with regard
      to DC2000CE orientation, movement, and vibration were identified. Vibrating the
      DC2000CE while measuring aerosol concentrations may cause an increase of ~35
      mm(2) m(-3), whereas moving the DC2000CE may cause concentrations to be inflated
      by as much as 400 mm(2) m(-3). Depending on the concentration of the aerosol of
      interest being measured, moving or vibrating a DC2000CE while measuring the
      aerosol should be avoided.

PMID- 24458323
TI  - Studies in seed dormancy : VIII. The identification and determination of
      gibberellins A1 and A 9 in seeds of Corylus avellana L.
AB  - The three major fractions (II, III and V) of the five fractions of gibberellin
      (GA)-like activity obtained by the thin layer chromatographic purification of an
      extract of hazel embryos have been examined by gas liquid chromatography and
      combined gas chromatography-mass spectrometry. By these techniques GA1 was
      identified as the methyl ester trimethylsilyl ether in fraction II and GA9 as the
      methyl ester in fraction V. Both substances were clearly separated from other
      components by gas liquid chromatography so that accurate determination of their
      concentrations was possible. GA1 accounted for most of the activity found by
      bioassay in fraction II while GA9 accounted for only part of the activity of
      fraction V. The GA-like substances in the less biologically active thin layer
      chromatography fractions have not yet been identified.Freshly harvested seeds
      contained GA1 but GA9 was not detected. After 28 days dry storage and 42 days
      imbibition and chilling at 5 degrees , the GA1 content was very low and GA9 was
      still below the limits of detection. On subsequent exposure of the seeds to a
      temperature of 20 degrees  for 8 days, there was a 40-fold increase of GA1 and at
      least a 300-fold increase of GA9. 

PMID- 24458324
TI  - Metabolic events in synchronised cell cultures of Acer pseudoplatanus L.
AB  - Cell division was synchronised in 4-litre batch cultures of Acer pseudoplatanus
      L. by starvation and regrowth. Up to five consecutive cell cycles were observed
      in each culture. Mitosis and cytokinesis were synchronised within 0.2 cell
      cycles. Accumulation of extractable DNA was discontinuous and separate from
      cytokinesis. Correction for the degree of synchrony in the population gave: G1=13
      37 h, S=15 h, G2=14-19 h and M=0.9-1.3 h. Thymidine kinase activity and
      [(14)C]thymidine incorporation were highest during S-phase. A peak of activity of
      aspartate transcarbamoylase occurred during G2. Peaks in succinate dehydrogenase
      activity and respiration rate were observed at the initiation of DNA synthesis
      and just prior to mitosis. The activity of glucose-6-phosphate dehydrogenase
      doubled in one step during the cell cycle. Total RNA and protein accumulated
      continuously through the cell cycle; the final rate being twice that observed
      initially. 

PMID- 24458325
TI  - Carbon dioxide fixation by epidermal and mesophyll tissues of Tulipa and
      Commelina.
AB  - Rates of (14)CO2 fixation by epidermal tissue of Tulipa gesneriana (tulip) and
      Commelina diffusa are only slightly higher in the light than in the dark while in
      mesophyl tissues rates are much greater in the light. The first products of
      (14)CO2 fixation by epidermal tissue of Tulipa gesneriana and C. diffusa in the
      light and dark are malate and aspartate. In addition to these dominating
      dicarboxylic acids, 3-phosphoglyceric acid and sugar phosphates appear in the
      light, while in the dark only the amino acids, glutamate and glutamine become
      labelled. Mesophyll tissue of tulip and C. diffusa, however, gives typical CO2
      fixation patterns of the labelled products of C3 plants. Furthermore, a period of
      dark (14)CO2 fixation followed by a light (12)CO2 chase carried out with
      epidermal tissue suggested that malate can act has the precursor of
      phosphorylated compounds of the Calvin cycle and consequently of starch. The data
      are consistent with the view that guard cells are able to exhibit Crassulacean
      acid metabolism. 

PMID- 24458326
TI  - Structural changes accompanying infection of tobacco protoplasts with two
      spherical viruses.
AB  - Ultrastructural changes occurring in isolated tobacco leaf protoplasts following
      infection with cowpea chlorotic mottle virus and bromegrass mosaic virus variant
      5, have been examined. Only the endoplasmic reticulum/nuclear membrane complex
      has shown a consistent series of changes in structure and distribution. Both
      viruses induce proliferation of the endoplasmic reticulum and its modification.
      The nuclear membrane gives rise to small cytoplasmic vacuoles probably containing
      nucleic acid by a process of blebbing involving both its inner and outer
      membrane. This is a prominent feature of CCMV infection. BMV5 infection is
      particularly characterised by the appearance of local organised arrays of
      assembled virus particles. The results are discussed in terms of possible
      nucleocytoplasmic interactions. 

PMID- 24458327
TI  - Lettuce seed germination and cytokinins: their entry and formation.
AB  - Cytokinins overcome the inhibitory effect of abscisic acid on the germination of
      isolated embryos of Grand Rapids lettuce. We have used this fact to assess the
      content of cytokinins in embryos removed from intact seeds which have been
      supplied with these growth substances i.e. to determine hormonal uptake. The
      method has also been used to examine the hypothesis that phytochrome and
      gibberellin lead to increases in active cytokinin levels in seeds. Appreciable
      amounts of cytokinins enter intact seeds yet seem unable to promote germination.
      On the other hand, little or no cytokinin-like activity seems to result from
      light or gibberellin treatments. We conclude that there are unresolved
      difficulties inherent in the "cytokinin hypothesis" of phytochrome and
      gibberellin action. 

PMID- 24458328
TI  - [Electron-microscopical investigation on wax-covered stomatas].
AB  - The wax structure of plant leaves has been investigated by scanning electron
      microscopy and with the replica technique by transmission electron microscopy. In
      addition to replicas of the wax layer, replicas of the leaf surface after removal
      of the wax have been examined.The wax layer is very thick and felt-like,
      especially when the plants have been grown at low humidity. In this case the
      stomatas are also smaller than those of plants grown at high humidity.The amount
      of transpiration of leaves was correlated to the different formation of the wax
      layer. Thick and felt-like structure of the wax above the stomatas reduces the
      water loss considerably. On the other hand all water evaporates from leaves in a
      short time after removal of the wax. 

PMID- 24458329
TI  - Chloride transport in Anacystis nidulans.
AB  - Anacystis nidulans will take up and accumulate chloride ions. When the external
      concentration was 0.2 mM Cl(-) the level in the cells was 2.8 mM Cl(-) and under
      these conditions the flux across the cell surface was in the region of 10(
      13)equiv Cl(-).sec(-1).cm(-2). It is suggested that this Cl(-) influx is active
      and operates against an electrochemical potential gradient estimated to be 117 mV
      or 2.68 kcal/mole. The uptake of (36)Cl was inhibited by low temperatures and
      there was a net loss of Cl(-) from the cells with the level decreasing towards
      the equilibrium value as estimated from K(+) distribution. Although the active
      influx of Cl(-) was often stimulated by light this was not always the case. Dark
      storage treatment and regulation of the chlorophyll a/phycocyanin ratios as well
      as total pigment content of the cells did not clarify the conditions which
      brought about light stimulation. Moreover, the metabolic inhibitors CCCP and CMU
      and also the use of anaerobic conditions did not clearly indicate the
      relationship between the influx mechanism and light-dark metabolism and no firm
      conclusions could be made about the nature of the energy source. The variation in
      the degree of light stimulation probably reflects the fact that in this
      procaryotic organism the photosynthetic and respiratory units are located on the
      same membrane systems and are in very close proximity to the probable site of the
      Cl(-) pump, the plasmalemma. 

PMID- 24458330
TI  - Inhibition of gamete formation by cycloheximide in pollen tubes of Impatients
      balsamina.
AB  - Cycloheximide (CH) inhibited the division of generative cell in pollen cultures
      of Impatiens balsamina in concentrations of 1-200 MUg/ml without affecting pollen
      germination or pollen tube growth. This inhibition was reversible up to 3 h in
      hanging drop cultures and up to 6 h in test tube cultures by replacement of the
      medium with a CH-free one. 

PMID- 24458331
TI  - Characterization of abscisic acid in chloroplasts of Pisum sativum L. cv. Alaska
      by combined gas-chromatography-mass spectrometry.
AB  - Abscisic acid was characterized from extracts of isolated pea chloroplasts by
      combined gas-chromatography-mass spectrometry. By single ion monitoring of the
      base peak (m/e 190) in the mass spectrum, 8.6 MUg ABA were detected in
      chloroplasts isolated from 1 kg fresh weight of pea shoots. 

PMID- 24458332
TI  - Root-growth inhibitors from root tips of Zea mays L.
AB  - At least two root-growth-inhibiting substances have been detected in extracts of
      Zea mays root tips. One has chromatographic properties similar to those of
      abscisic acid (ABA) and is largely confined to the cap. Another, which has not
      been identified, is present in the root apex but not in the cap. Indole-3yl
      acetic acid (IAA) is never detected in the root cap. Xanthoxin may be present in
      the root tip. 

PMID- 24458333
TI  - Effective impedance boundary optimization and its contribution to dipole
      radiation and radiation pattern control.
AB  - Radiation pattern control has generated much interest recently due to its
      potential applications. Here we report the observation of high-efficiency dipole
      like radiation of sound with broad bandwidth through a decorated plate with
      periodical two-dimensional Helmholtz resonators on both sides and a single slit
      at the centre. The decorated plate was optimally designed to adjust the effective
      impedance of the boundary, and the underlying mechanism of radiation pattern
      control is attributed to wave vector tailoring. The high radiation efficiency is
      due to the Fabry-Perot resonances associated with waveguide modes in the centre
      slit. The method to obtain a collimated beam without any sidelobes is also
      provided. Our findings should have an impact on acoustic applications. 

PMID- 24458334
TI  - Association of ankle kinematics and performance on the y-balance test with
      inclinometer measurements on the weight-bearing-lunge test.
AB  - CONTEXT: Ankle-dorsiflexion range of motion has often been measured in the weight
      bearing condition in the clinical setting; however, little is known about the
      relationship between the weight-bearing-lunge test (WBLT) and both ankle
      kinematics and performance on dynamic postural-control tests. OBJECTIVE: To
      examine whether ankle kinematics and performance on the Lower Quarter Y-Balance
      Test (YBT-LQ) are correlated with results of the WBLT using an inclinometer and
      tape measure. DESIGN: Cross-sectional. SETTING: University motion-analysis
      laboratory. PARTICIPANTS: 30 physically active participants. INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: The WBLT was evaluated using an inclinometer and a tape
      measure. The reach distances in the anterior, posteromedial, and posterolateral
      directions on the YBT-LQ were normalized by limb length. Ankle dorsiflexion
      during the YBT-LQ was recorded using a 3-dimensional motion-analysis system.
      Simple linear regression was used to examine the relationship between the WBLT
      results and both ankle dorsiflexion and the normalized reach distance in each
      direction on the YBT-LQ. RESULTS: The WBLT results were significantly correlated
      with ankle dorsiflexion in all directions on the YBT-LQ (P < .05). A strong
      correlation was found between the inclinometer measurement of the WBLT and ankle
      dorsiflexion (r = .74, r2 = .55), whereas the tape-measure results on the WBLT
      were moderately correlated with ankle dorsiflexion (r = .64, r2 = .40) during the
      anterior reach on the YBT-LQ. Only the normalized anterior reach distance was
      significantly correlated with the results for the inclinometer (r = .68, r2 =
      .46) and the tape measure (r = .64, r2 = .41) on the WBLT. CONCLUSIONS:
      Inclinometer measurements on the WBLT can be an appropriate tool for predicting
      the amount of ankle dorsiflexion during the YBT-LQ. Furthermore, WBLT should be
      measured in those who demonstrate poor dynamic balance.

PMID- 24458335
TI  - Scapular dyskinesis and SICK syndrome in patients with a chronic type III
      acromioclavicular dislocation. Results of rehabilitation.
AB  - PURPOSE: Scapular dyskinesis has been related to acromioclavicular injuries. A
      rehabilitation protocol has been studied in order to treat scapular dyskinesis,
      but it has not yet been evaluated. This rehabilitation programme was adopted to
      improve the shoulder function, thereby improving the scapular dyskinesis in
      patients with chronic acromioclavicular dislocation. METHOD: Twenty-four patients
      diagnosed with chronic type III acromioclavicular dislocation and scapular
      dyskinesis that have already been conservatively treated were enrolled in the
      rehabilitation protocol and analysed. Fourteen of these patients had a Scapular
      Inferior Coracoid dysKinesis (SICK) Syndrome. The adopted rehabilitation protocol
      consisted of 12 strengthening and stretching exercises of the scapulae. The final
      follow-ups were performed after 6 weeks, 6 months and 12 months using clinical
      measurements of scapular position and clinical evaluation of the scapular motion.
      In order to evaluate the SICK scapula syndrome, we used the SICK Scapula Rating
      Scale. The shoulder function was evaluated with a Constant Score and a Subjective
      Shoulder Value. RESULTS: After 12 months, the follow-up concluded that the
      scapular dyskinesis was no longer present in 18/23 patients (78.2 %). SICK
      scapula syndrome was observed in 4/8 patients with a scapular malposition. The
      Scapula Rating Scale score in 4 patients with SICK scapula was 7.5 points. After
      12 months of rehabilitation, the mean Constant Score and Subjective Shoulder
      Value grew up to 85 points. CONCLUSION: The scapular dyskinesis and SICK syndrome
      secondary to chronic type III AC dislocation can be treated with the proposed
      rehabilitation protocol resulting in positive improvements of the shoulder
      function within 6 weeks; however, patients that do not respond to the
      rehabilitation programme will not improve with extended rehabilitation time. It
      is important to advise patients of the specific exercises for the
      prevention/treatment of scapular dyskinesis in the rehabilitation programme after
      AC joint dislocation. LEVEL OF EVIDENCE: IV.

PMID- 24458336
TI  - Recent advances in porous Pt-based nanostructures: synthesis and electrochemical
      applications.
AB  - Porous Pt-based nanostructured materials possess intriguing physical and chemical
      properties to generate promising potential for various important applications
      such as fuel cells, sensors, stimulation electrodes, mechanical actuators and
      catalysis. With the great advances in material science and nanotechnology, porous
      Pt-based nanomaterials with well-controlled composition, shape, and geometrical
      configuration have been rationally designed and fabricated. Importantly, their
      superior properties including unique pore structure, large specific surface area
      and excellent structural stability have fuelled up great interest to improve
      their current performance and to explore new applications. This tutorial review
      attempts to summarize the recent important progress towards the development of
      porous Pt-based nanostructured materials, with special emphasis on fabrication
      methods and advanced electrochemical applications, such as electrocatalysis and
      electrochemical sensors. The correlations between the composition and morphology
      of the catalysts and their catalytic properties are discussed based on some
      important and representative examples. Some key scientific issues and potential
      future directions of research in this field are also discussed. 

PMID- 24458337
TI  - Hybridization of a flexible cyclooctatetraene core and rigid aceneimide wings for
      multiluminescent flapping pi systems.
AB  - The hybridization of flexible and rigid pi-conjugated frameworks is a potent
      concept for producing new functional materials. In this article, a series of
      multifluorescent flapping pi systems that combine a flexible cyclooctatetraene
      (COT) core and rigid aceneimide wings with various pi-conjugation lengths has
      been designed and synthesized, and their structure/properties relationships have
      been investigated. Whereas these molecules have a V-shaped bent conformation in
      the ground state, the bent structure changes to a planar conformation in the
      lowest excited singlet (S1 ) state irrespective of the lengths of the aceneimide
      wings. However, the fluorescence behavior in solution is distinct between the
      naphthaleneimide system and the anthraceneimide system. The former has a
      nonemissive S1 state owing to the significant contribution of the antiaromatic
      character of the planar COT frontier molecular orbitals, thereby resulting in
      complete fluorescence quenching in solution. In contrast, the latter
      anthraceneimide system shows an intense emission, which is ascribed to the planar
      but distorted S1 state that shows the allowed transition between the pi-molecular
      orbitals delocalized over the COT core and the acene wings. The other
      characteristic of these pi systems is the significantly redshifted fluorescence
      in the crystalline state relative to their monomer fluorescence. The relationship
      between the packing structures and the fluorescence properties was investigated
      by preparing a series of hybrid pi systems with different sizes of substituents
      on the imide moieties, which revealed the effect of the twofold pi-stacked
      structure of the V-shaped molecules on the large bathochromic shift in emission. 

PMID- 24458338
TI  - Blended learning in health education: three case studies.
AB  - Blended learning in which online education is combined with face-to-face
      education is especially useful for (future) health care professionals who need to
      keep up-to-date. Blended learning can make learning more efficient, for instance
      by removing barriers of time and distance. In the past distance-based learning
      activities have often been associated with traditional delivery-based methods,
      individual learning and limited contact. The central question in this paper is:
      can blended learning be active and collaborative? Three cases of blended, active
      and collaborative learning are presented. In case 1 a virtual classroom is used
      to realize online problem-based learning (PBL). In case 2 PBL cases are presented
      in Second Life, a 3D immersive virtual world. In case 3 discussion forums, blogs
      and wikis were used. In all cases face-to-face meetings were also organized.
      Evaluation results of the three cases clearly show that active, collaborative
      learning at a distance is possible. Blended learning enables the use of novel
      instructional methods and student-centred education. The three cases employ
      different educational methods, thus illustrating diverse possibilities and a
      variety of learning activities in blended learning. Interaction and communication
      rules, the role of the teacher, careful selection of collaboration tools and
      technical preparation should be considered when designing and implementing
      blended learning. 

PMID- 24458340
TI  - Interactions among leaf photosynthetic rates, flowering and pod set in soybeans.
AB  - The seasonal maximum in photosynthetic CO2 exchange rate (CER) and the cessation
      of leaf expansion in soybeans (Glycine max (L.) Merr) accompany fruiting under
      normal agricultural conditions. To investigate whether these phenomena were
      obligatively tied together, we caused early flowering of long-season varieties by
      imposing artificial short-day treatments. Comparisons of CER and leaf area
      between vegetative (long-day treatment) and fruiting (short-day treatment) plants
      of long-season cultivar confirmed the relationship of these phenomena. The same
      comparisons made between a long-season and a short-season cultivar, both at the
      same daylength, also confirmed the relationship. 

PMID- 24458339
TI  - [Ventricular tachycardia in postinfarction patients and coronary heart disease.
      Treatment and prognostic significance].
AB  - Patients with coronary heart disease are subject to an increased risk for sudden
      cardiac death (SCD). Within the first 30-90 days after the myocardial infarct the
      risk is particularly high. In times of implantable cardioverter-defibrillator
      (ICD) on the one hand and the ability to bridge high-risk periods with e. g.
      wearable defibrillator vests on the other, adequate risk stratification is
      essential. Currently, the main parameter for this is the left ventricular
      ejection fraction (LVEF). However, risk stratification by measurement of the LVEF
      has severe limitations, especially since the majority of patients suffering from
      SCD have a normal LVEF. Various other methods like ventricular ectopy, signal
      averaged ECG, QRS width, microvolt T-wave alternans and programmed ventricular
      stimulation have been previously evaluated. None of these methods alone or in
      combination with a left ventricular function assessment was capable of improving
      the predictability of arrhythmic events significantly. Considering the multiple
      mechanisms that can lead to SCD, a single risk stratifier seems unrealistic.
      However, patients with chronic total occlusion of a coronary artery and residual
      or provocable ischemia have an increased risk for SCD. Therefore a combination of
      clinical and angiographic parameters seems reasonable. Advanced echocardiographic
      parameters e.g. mechanical dispersion could be used on a complementary role.

PMID- 24458341
TI  - Antenna chlorophyll a complexes in mutant and developing barley.
AB  - The chlorophyll a antenna of photosystems I and II were each isolated after
      detergent treatment by gel electrophoresis or sucrose gradient centrifugation
      from a b-less mutant of barley grown in daylight and from wildtype barley
      developed in intermittent light. We identified each fraction by both its
      electrophoretic position and PS I activity (P700 content) in the case of the
      mutant, and by both PS I and PS II activity (DCIP reduction from DPC) in the
      light-limited plants. The proportion of Chl a in each photosystem was estimated
      from the amount in each gel or sucrose gradient band, and from addition of the
      areas under the absorption spectra (650-710 nm) of each fraction to match the
      spectrum of the solubilized thylakoids. The latter method was possible because
      the spectrum (77 K) of each fraction was unique; in the mutant about 70% of
      chlorophyll is associated with PS I and 30% with PS II. In the light-limited
      plants, the reverse is true with nearly 70% associated with PS II. RESOL analyses
      of both absorption and fluorescence emission spectra of all isolated fractions
      indicated an abnormal arrangement of antenna chlorophyll molecules in the light
      limited, developing membranes even though their reaction centers are fully
      functional. 

PMID- 24458342
TI  - Inhibition of C4 photosynthesis by (benzamidooxy)acetic acid.
AB  - (Benzamidooxy)acetic acid (common name benzadox) which has herbicidal properties
      was evaluated as a potential inhibitor of photosynthesis in C4 plants. Among
      enzymes of the C4 pathway, it was a relatively strong inhibitor of alanine
      aminotransferase in in vitro experiments at concentrations of 5mM. In benzadox
      treated leaves of Panicum miliaceum, a NAD-malic enzyme type C4 species, there
      was strong inhibition of both alanine and aspartate aminotransferase and of
      photosynthetic O2 evolution within one hour. Consistent with the inhibition of
      these enzymes of the C4 cycle, the pool sizes of metabolites of the cycle was
      altered: the aspartate level was increased two fold, while the levels of other
      metabolites such as pyruvate, alanine, oxalacetate and malate were decreased.
      Kinetic studies with partially purified alanine aminotransferase showed that
      benzadox is a competitive inhibitor with respect to alanine and a noncompetitive
      inhibitor with respect to 2-oxoglutarate. Comparisons between the structures and
      inhibitory actions of benzadox and (aminooxy)acetic acid, the latter a potent
      inhibitor of alanine and aspartate aminotransferases, suggest that in vivo,
      benzadox may exert its effect through metabolism to (aminooxy)acetic acid. 

PMID- 24458343
TI  - Photosynthesis at ambient and elevated humidity over a growing season in soybean.
AB  - Daytime rates of net photosynthesis of upper canopy leaflets of soybeans were
      compared on 17 days for leaflets exposed to air at the ambient humidity and at a
      higher humidity. Leaflets at the higher humidity had higher rates of net
      photosynthesis on 16 of the 17 days. The daily total of net photosynthesis of
      leaflets at the higher humidity was on average 1.32 times that for leaflets at
      ambient humidity. A strong limitation of net photosynthesis by ambient humidity
      was found throughout the growing season. 

PMID- 24458344
TI  - Effect of light and darkness on nitrate assimilation by Rhodopseudomonas
      capsulata E1F1.
AB  - The photosynthetic nonsulfur purple bacterium Rhodopseudomonas capsulata strain
      E1F1 assimilated nitrate or nitrite only in illuminated cultures under anaerobic
      conditions. The bacterial cells grew aerobically in the dark only when ammonia or
      other forms of reduced nitrogen were present in the medium. However, nitrate
      reductase was detected either in light-anaerobic or in dark-aerobic conditions
      upon addition of nitrate to the media. Changes from light-anaerobic to dark
      aerobic conditions and vice versa markedly influenced growth, nitrate uptake and
      the nitrate reductase levels. Growth on nitrate in the light and nitrate
      reductase activity were dependent on the presence of molybdenum in the medium
      whereas the addition of tungstate inhibited both growth and enzyme activity. 

PMID- 24458345
TI  - Changes in properties of phosphoenolpyruvate carboxylase from the CAM plant Sedum
      praealtum D.C. upon dark/light transition and their stabilization by glycerol.
AB  - A prenounced decrease in phosphoenolpyruvate earboxylase (PEPC) activity is
      observed upon dark/light transition in Sedum praealtum D.C., only when glycerol
      is included in the extraction medium. If glycerol is omitted, the activity
      extracted in light is initially low, but soon reaches night levels. The
      stabilization of the light-induced form of the enzyme by glycerol, in crude or
      desalted extracts, made it possible to study its kinetic properties in comparison
      to those of the dark form. The behaviour towards substrate (PEP) changes from
      hyperbolic (dark) to sigmoid (light), S0.5 is increased and the enzymic activity
      becomes more sensitive to malate inhibition. Quite different activity/pH profiles
      are also obtained for the two forms of PEPC.It is inferred that the in vivo
      regulation of PEPC in CAM is effected by a concerted action of light, malate and
      pH shifting. 

PMID- 24458346
TI  - pH effects on light dependence of the stoichiometry of proton influx and efflux
      to electron transport in spinach chloroplasts.
AB  - Initial and steady state rates of proton transport at low light intensity have
      been measured and compared with steady state rates of electron transport in the
      pH range of 6.0-7.6 in envelope-free spinach chloroplasts. At pH 6-7, the H(+)/e(
      ) values computed using the initial rate of proton transport varied with light
      intensity, from a value of 2 at low light to almost 5 at high light. In contrast,
      the H(+)/e(-) values computed using the steady state rate of proton transport did
      not show a dependence on light intensity, having a constant value of 1.7+/-0.2.
      Likewise, at pH 7.6, the H(+)/e(-) ratio, computed using either the initial or
      steady state rates of proton transport did not vary with light intensity but was
      constant at H(+)/e(-)=1.7+/-0.1. Analysis of the light dependence of electron and
      proton transport allowed determination of (a) the quantam requirements of
      transport, (b) the rates of transport at light saturation, and (c) H(+)/e(-)
      ratios for initial and steady state proton transport. Extrapolating the initial
      proton transport to zero light, we found that both H(+)/photon and H(+)/e(-)
      values were not strongly dependent on pH, approaching a near constant value of
      2.0. Using the initial rate of proton transport extrapolated to saturating light
      intensity we found the H(+)/e(-) ratio to be strongly pH-dependent. We suggest
      that internal pH controls electron transport at high light intensities. The true
      stoichiometry is reflected only in measurements taken at low light using the
      initial proton transport data. Our findings and interpretation reconcile some
      conflicting data in the literature regarding the pH-dependence of the H(+)/e(-)
      ratio and support the concept that internal pH controls noncyclic electron
      transport. 

PMID- 24458347
TI  - Mode of action of photosynthesis inhibiting 4-hydroxy-benzonitriles containing
      nitro group.
AB  - The effects of 3,5-disubstituted 4-hydroxy-benzonitriles - bromoxynil and
      compounds containing nitro group - on some photosynthetic parameters of spinach
      and wheat were investigated. There is considerable difference in the effectivity
      of the compounds even at the level of chloroplasts. On the basis of their effect
      on the development of CO2 fixation of greening wheat seedlings bromoxynil and 3,5
      dinitro-4-hydroxy-derivative were ineffective, while the asymmetric - 3-nitro-5
      halogenic-substituted - compounds showed a strong effectivity. The bromine and
      iodine containing asymmetric compounds reduced the intensity of the short
      wavelength fluorescence. All asymmetric compounds shifted the long wavelength
      fluorescence maximum with 5-8 nm to shorter wavelength. These results refer to
      inhibition of formation of chlorophyll forms absorbing at longer wavelengths and
      to the change in the conditions of energy migration. The ultrastructure of the
      chloroplasts in the treated seedlings became similar to the shade adapted
      chloroplasts. 

PMID- 24458348
TI  - Localization of membrane-bound cytochromes of photosynthetic bacterium Chromatium
      vinosum.

PMID- 24458350
TI  - Editorial note.

PMID- 24458349
TI  - Glycolate excretion by air-grown Euglena graeilis z.
AB  - In contrast to reported fact, the air-grown cells of Euglena gracilis z were
      found to excrete glycolate into the surrounding medium, when placed in an
      atmosphere of 100% O2 under illumination at 20000 lux at the same rate of the 5%
      CO2-grown cells, but with a lag phase of about 30 min. The lag was eliminated by
      lowering intracellular CO2 concentration in the air-grown cells. 

PMID- 24458351
TI  - Effects of (20S*,24R*)-epoxy-9,19-cyclolanstane-3beta,12beta,16beta,25-pentaol-3
      O-beta-D-xylopyranoside extracted from rhizoma Beesia on immunoregulation and
      anti-inflammation.
AB  - (20S*,24R*)-epoxy-9,19-cyclolanstane-3beta,12beta,16beta,25-pentaol-3-O-beta-D
      xylopyranoside (BC1) is a kind of natural bioactive substance extracted from
      Beesia calthaefolia (Maxim.)Ulbr. This study was designed to evaluate the effects
      of BC1 on the proliferation of lymphocytes, phagocytosis of peritoneal
      macrophage, and cytokine secretion, such as tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-1beta, and the foot pad thickness index, which is beneficial for
      understanding the mechanism of BC1 on immunoregulation and anti-inflammation and
      also will benefit our further research. The proliferation of splenic lymphocyte
      induced by mitogen (concanavalin A or lipopolysaccharide (LPS)) was detected
      using the cell counting kit assay. The neutral red phagocytic test of macrophages
      was determined by colorimetric method. The gene and protein expressions of TNF
      alpha and IL-1beta were measured by real time RT-PCR and ELISA in serum, spleen,
      and lymphocytes, respectively. In vitro, our present study has shown that BC1
      (31.25-250 MUg/ml) could inhibit the proliferation of splenic lymphocyte and
      phagocytosis of macrophages, and inhibit the increased production of TNF-alpha
      and IL-1beta in protein and gene levels. In mice, LPS could increase the gene and
      protein expressions of TNF-alpha and IL-1beta, respectively, but BC1 (12.5-50
      MUg/kg) could recover the increased gene and protein expressions of TNF-alpha and
      IL-1beta induced by LPS in the spleen and serum of mice. Treatment of arthritic
      rats with BC1 (1.5 mg/kg body weight) resulted in a significant reduction in foot
      pad thickness index and serum TNF-alpha level comparable to the indomethacin
      treated arthritic rats, proving its anti-inflammatory effect. Thus, the function
      of immunoregulation of BC1 may be accomplished through modulating the gene and
      protein expressions of TNF-alpha and IL-1beta.

PMID- 24458352
TI  - [Letter to the contribution of Bender B, Beschorner R, Honegger J, Heckl S,
      Ernemann U, Horger M. New WHO entities of the CNS in neuroradiology. Fortschr
      Rontgenstr 2013, 11: 1021].

PMID- 24458353
TI  - Circadian misalignment augments markers of insulin resistance and inflammation,
      independently of sleep loss.
AB  - Shift workers, who are exposed to irregular sleep schedules resulting in sleep
      deprivation and misalignment of circadian rhythms, have an increased risk of
      diabetes relative to day workers. In healthy adults, sleep restriction without
      circadian misalignment promotes insulin resistance. To determine whether the
      misalignment of circadian rhythms that typically occurs in shift work involves
      intrinsic adverse metabolic effects independently of sleep loss, a parallel group
      design was used to study 26 healthy adults. Both interventions involved 3
      inpatient days with 10-h bedtimes, followed by 8 inpatient days of sleep
      restriction to 5 h with fixed nocturnal bedtimes (circadian alignment) or with
      bedtimes delayed by 8.5 h on 4 of the 8 days (circadian misalignment). Daily
      total sleep time (SD) during the intervention was nearly identical in the aligned
      and misaligned conditions (4 h 48 min [5 min] vs. 4 h 45 min [6 min]). In both
      groups, insulin sensitivity (SI) significantly decreased after sleep restriction,
      without a compensatory increase in insulin secretion, and inflammation increased.
      In male participants exposed to circadian misalignment, the reduction in SI and
      the increase in inflammation both doubled compared with those who maintained
      regular nocturnal bedtimes. Circadian misalignment that occurs in shift work may
      increase diabetes risk and inflammation, independently of sleep loss.

PMID- 24458354
TI  - Evaluating the role of epigenetic histone modifications in the metabolic memory
      of type 1 diabetes.
AB  - We assessed whether epigenetic histone posttranslational modifications are
      associated with the prolonged beneficial effects (metabolic memory) of intensive
      versus conventional therapy during the Diabetes Control and Complications Trial
      (DCCT) on the progression of microvascular outcomes in the long-term Epidemiology
      of Diabetes Interventions and Complications (EDIC) study. We performed chromatin
      immunoprecipitation linked to promoter tiling arrays to profile H3 lysine-9
      acetylation (H3K9Ac), H3 lysine-4 trimethylation (H3K4Me3), and H3K9Me2 in blood
      monocytes and lymphocytes obtained from 30 DCCT conventional treatment group
      subjects (case subjects: mean DCCT HbA1c level >9.1% [76 mmol/mol] and
      progression of retinopathy or nephropathy by EDIC year 10 of follow-up) versus 30
      DCCT intensive treatment subjects (control subjects: mean DCCT HbA1c level <7.3%
      [56 mmol/mol] and without progression of retinopathy or nephropathy). Monocytes
      from case subjects had statistically greater numbers of promoter regions with
      enrichment in H3K9Ac (active chromatin mark) compared with control subjects (P =
      0.0096). Among the patients in the two groups combined, monocyte H3K9Ac was
      significantly associated with the mean HbA1c level during the DCCT and EDIC (each
      P < 2.2E-16). Of note, the top 38 case hyperacetylated promoters (P < 0.05)
      included >15 genes related to the nuclear factor-kappaB inflammatory pathway and
      were enriched in genes related to diabetes complications. These results suggest
      an association between HbA1c level and H3K9Ac, and a possible epigenetic
      explanation for metabolic memory in humans. 

PMID- 24458355
TI  - Decreasing cx36 gap junction coupling compensates for overactive KATP channels to
      restore insulin secretion and prevent hyperglycemia in a mouse model of neonatal
      diabetes.
AB  - Mutations to the ATP-sensitive K(+) channel (KATP channel) that reduce the
      sensitivity of ATP inhibition cause neonatal diabetes mellitus via suppression of
      beta-cell glucose-stimulated free calcium activity ([Ca(2+)]i) and insulin
      secretion. Connexin-36 (Cx36) gap junctions also regulate islet electrical
      activity; upon knockout of Cx36, beta-cells show [Ca(2+)]i elevations at basal
      glucose. We hypothesized that in the presence of overactive ATP-insensitive KATP
      channels, a reduction in Cx36 would allow elevations in glucose-stimulated
      [Ca(2+)]i and insulin secretion to improve glucose homeostasis. To test this, we
      introduced a genetic knockout of Cx36 into mice that express ATP-insensitive KATP
      channels and measured glucose homeostasis and islet metabolic, electrical, and
      insulin secretion responses. In the normal presence of Cx36, after expression of
      ATP-insensitive KATP channels, blood glucose levels rapidly rose to >500 mg/dL.
      Islets from these mice showed reduced glucose-stimulated [Ca(2+)]i and no insulin
      secretion. In mice lacking Cx36 after expression of ATP-insensitive KATP
      channels, normal glucose levels were maintained. Islets from these mice had near
      normal glucose-stimulated [Ca(2+)]i and insulin secretion. We therefore
      demonstrate a novel mechanism by which islet function can be recovered in a
      monogenic model of diabetes. A reduction of gap junction coupling allows
      sufficient glucose-stimulated [Ca(2+)]i and insulin secretion to prevent the
      emergence of diabetes. 

PMID- 24458357
TI  - Induction of mixed chimerism depletes pre-existing and de novo-developed
      autoreactive B cells in autoimmune NOD mice.
AB  - Destruction of pancreatic islet beta-cells in type 1 diabetes (T1D) is mainly
      mediated by autoimmune T and B lymphocytes. We reported that induction of major
      histocompatibility complex (MHC)-mismatched mixed chimerism reversed autoimmunity
      and reestablished thymic negative selection of autoreactive T cells in NOD mice,
      but it is still unclear how mixed chimerism tolerizes autoreactive B cells. The
      current studies were designed to reveal the mechanisms on how mixed chimerism
      tolerizes autoreactive B cells in T1D. Accordingly, mixed chimerism was induced
      in NOD mice through radiation-free nonmyeloablative anti-CD3/CD8 conditioning and
      infusion of donor CD4(+) T cell-depleted spleen and whole bone marrow (BM) cells
      or through myeloablative total body irradiation conditioning and reconstitution
      with T cell-depleted BM cells from donor and host. Kinetic analysis of percentage
      and yield of preplasma and plasma B cells, newly developed B-cell subsets, and
      their apoptosis was performed 30-60 days after transplantation. Induction of MHC
      mismatched mixed chimerism results in depleting host-type pre-existing preplasma
      and plasma B cells as well as augmenting apoptosis of immature transitional T1 B
      cells, including insulin-specific B cells in a donor B cell-dependent manner.
      Therefore, induction of MHC-mismatched mixed chimerism depletes pre-existing and
      de novo-developed autoreactive B cells.

PMID- 24458356
TI  - Glycogen synthase kinase-3beta inhibition ameliorates cardiac parasympathetic
      dysfunction in type 1 diabetic Akita mice.
AB  - Decreased heart rate variability (HRV) is a major risk factor for sudden death
      and cardiovascular disease. We previously demonstrated that parasympathetic
      dysfunction in the heart of the Akita type 1 diabetic mouse was due to a decrease
      in the level of the sterol response element-binding protein (SREBP-1). Here we
      demonstrate that hyperactivity of glycogen synthase kinase-3beta (GSK3beta) in
      the atrium of the Akita mouse results in decreased SREBP-1, attenuation of
      parasympathetic modulation of heart rate, measured as a decrease in the high
      frequency (HF) fraction of HRV in the presence of propranolol, and a decrease in
      expression of the G-protein coupled inward rectifying K(+) (GIRK4) subunit of the
      acetylcholine (ACh)-activated inward-rectifying K(+) channel (IKACh), the ion
      channel that mediates the heart rate response to parasympathetic stimulation.
      Treatment of atrial myocytes with the GSK3beta inhibitor Kenpaullone increased
      levels of SREBP-1 and expression of GIRK4 and IKACh, whereas a dominant-active
      GSK3beta mutant decreased SREBP-1 and GIRK4 expression. In Akita mice treated
      with GSK3beta inhibitors Li(+) and/or CHIR-99021, Li(+) increased IKACh, and
      Li(+) and CHIR-99021 both partially reversed the decrease in HF fraction while
      increasing GIRK4 and SREBP-1 expression. These data support the conclusion that
      increased GSK3beta activity in the type 1 diabetic heart plays a critical role in
      parasympathetic dysfunction through an effect on SREBP-1, supporting GSK3beta as
      a new therapeutic target for diabetic autonomic neuropathy.

PMID- 24458358
TI  - The histone acetylase activator pentadecylidenemalonate 1b rescues proliferation
      and differentiation in the human cardiac mesenchymal cells of type 2 diabetic
      patients.
AB  - This study investigates the diabetes-associated alterations present in cardiac
      mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2
      diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator
      pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention
      to restore cellular function. D-CMSC were characterized by a reduced
      proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P),
      decreased differentiation potential, and premature cellular senescence. A global
      histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9
      (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of
      H3K9Ac and lysine 27 significantly increased. These observations were paralleled
      by a downregulation of the GCN5-related N-acetyltransferases (GNAT) p300/CBP
      associated factor and its isoform 5-alpha general control of amino acid synthesis
      (GCN5a), determining a relative decrease in total HAT activity. DNA CpG island
      hypermethylation was detected at promoters of genes involved in cell growth
      control and genomic stability. Remarkably, treatment with the GNAT proactivator
      SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG
      hypermethylation, and recovered D-CMSC proliferation and differentiation. These
      results suggest that epigenetic interventions may reverse alterations in human
      CMSC obtained from diabetic patients.

PMID- 24458359
TI  - Cdc2-like kinase 2 suppresses hepatic fatty acid oxidation and ketogenesis
      through disruption of the PGC-1alpha and MED1 complex.
AB  - Hepatic ketogenesis plays an important role in catabolism of fatty acids during
      fasting along with dietary lipid overload, but the mechanisms regulating this
      process remain poorly understood. Here, we show that Cdc2-like kinase 2 (Clk2)
      suppresses fatty acid oxidation and ketone body production during diet-induced
      obesity. In lean mice, hepatic Clk2 protein is very low during fasting and
      strongly increased during feeding; however, in diet-induced obese mice, Clk2
      protein remains elevated through both fed and fasted states. Liver-specific Clk2
      knockout mice fed a high-fat diet exhibit increased fasting levels of blood
      ketone bodies, reduced respiratory exchange ratio, and increased gene expression
      of fatty acid oxidation and ketogenic pathways. This effect of Clk2 is cell
      autonomous, because manipulation of Clk2 in hepatocytes controls genes and rates
      of fatty acid utilization. Clk2 phosphorylation of peroxisome proliferator
      activated receptor gamma coactivator (PGC-1alpha) disrupts its interaction with
      Mediator subunit 1, which leads to a suppression of PGC-1alpha activation of
      peroxisome proliferator-activated receptor alpha target genes in fatty acid
      oxidation and ketogenesis. These data demonstrate the importance of Clk2 in the
      regulation of fatty acid metabolism in vivo and suggest that inhibition of
      hepatic Clk2 could provide new therapies in the treatment of fatty liver disease.

PMID- 24458360
TI  - The Baf60c/Deptor pathway links skeletal muscle inflammation to glucose
      homeostasis in obesity.
AB  - Skeletal muscle insulin resistance in type 2 diabetes is associated with a shift
      from oxidative to glycolytic metabolism in myofibers. However, whether this
      metabolic switch is detrimental or adaptive for metabolic homeostasis has not
      been resolved. We recently demonstrated that the Baf60c/Deptor pathway promotes
      glycolytic metabolism in the muscle and protects mice from diet-induced insulin
      resistance. However, the nature of the signals that impinge on this pathway and
      the role of Baf60c in glucose homeostasis in the severe insulin-resistant state
      remain unknown. Here we show that expression of Baf60c and Deptor was
      downregulated in skeletal muscle in obesity, accompanied by extracellular signal
      related kinase (ERK) activation. In cultured myotubes, inhibition of ERK, but not
      Jun NH2-terminal kinase and IkappaB kinase, blocked the downregulation of Baf60c
      and Deptor by the proinflammatory cytokine tumor necrosis factor-alpha. Treatment
      of obese mice with the ERK inhibitor U0126 rescued Baf60c and Deptor expression
      in skeletal muscle and lowered blood glucose. Transgenic rescue of Baf60c in
      skeletal muscle restored Deptor expression and Akt phosphorylation and
      ameliorated insulin resistance in ob/ob mice. This study identifies the
      Baf60c/Deptor pathway as a target of proinflammatory signaling in skeletal muscle
      that may link meta-inflammation to skeletal myofiber metabolism and insulin
      resistance. 

PMID- 24458361
TI  - The extracellular matrix protein MAGP1 supports thermogenesis and protects
      against obesity and diabetes through regulation of TGF-beta.
AB  - Microfibril-associated glycoprotein 1 (MAGP1) is a component of extracellular
      matrix microfibrils. Here we show that MAGP1 expression is significantly altered
      in obese humans, and inactivation of the MAGP1 gene (Mfap2(-/-)) in mice results
      in adipocyte hypertrophy and predisposition to metabolic dysfunction. Impaired
      thermoregulation was evident in Mfap2(-/-) mice prior to changes in adiposity,
      suggesting a causative role for MAGP1 in the increased adiposity and
      predisposition to diabetes. By 5 weeks of age, Mfap2(-/-) mice were maladaptive
      to cold challenge, uncoupling protein-1 expression was attenuated in the brown
      adipose tissue, and there was reduced browning of the subcutaneous white adipose
      tissue. Levels of transforming growth factor-beta (TGF-beta) activity were
      elevated in Mfap2(-/-) adipose tissue, and the treatment of Mfap2(-/-) mice with
      a TGF-beta-neutralizing antibody improved their body temperature and prevented
      the increased adiposity phenotype. Together, these findings indicate that the
      regulation of TGF-beta by MAGP1 is protective against the effects of metabolic
      stress, and its absence predisposes individuals to metabolic dysfunction.

PMID- 24458362
TI  - GLP-1R-targeting magnetic nanoparticles for pancreatic islet imaging.
AB  - Noninvasive assessment of pancreatic beta-cell mass would tremendously aid in
      managing type 1 diabetes (T1D). Toward this goal, we synthesized an exendin-4
      conjugated magnetic iron oxide-based nanoparticle probe targeting glucagon-like
      peptide 1 receptor (GLP-1R), which is highly expressed on the surface of
      pancreatic beta-cells. In vitro studies in betaTC-6, the beta-cell line, showed
      specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared with
      nontargeted (termed MN-Cy5.5). In vivo magnetic resonance imaging showed a
      significant transverse relaxation time (T2) shortening in the pancreata of mice
      injected with the MN-Ex10-Cy5.5 probe compared with control animals injected with
      the nontargeted probe at 7.5 and 24 h after injection. Furthermore, DeltaT2 of
      the pancreata of prediabetic NOD mice was significantly higher than that of
      diabetic NOD mice after the injection of MN-Ex10-Cy5.5, indicating the decrease
      of probe accumulation in these animals due to beta-cell loss. Of note, DeltaT2 of
      prediabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly
      changed, reflecting the nonspecific mode of accumulation of nontargeted probe. We
      believe our results point to the potential for using this agent for monitoring
      the disease development and response of T1D to therapy. 

PMID- 24458363
TI  - Endogenous oils derived from human adipocytes are potent adjuvants that promote
      IL-1alpha-dependent inflammation.
AB  - Obesity is characterized by chronic inflammation associated with neutrophil and
      M1 macrophage infiltration into white adipose tissue. However, the mechanisms
      underlying this process remain largely unknown. Based on the ability of oil-based
      adjuvants to induce immune responses, we hypothesized that endogenous oils
      derived from necrotic adipocytes may function as an immunological "danger
      signal." Here we show that endogenous oils of human origin are potent adjuvants,
      enhancing antibody responses to a level comparable to Freund's incomplete
      adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1alpha
      dependent recruitment of neutrophils and M1-like macrophages, while
      simultaneously diminishing M2-like macrophages. We found that endogenous oils
      from subcutaneous and omental adipocytes, and from healthy and unhealthy obese
      individuals, promoted comparable inflammatory responses. Furthermore, we also
      confirmed that white adipocytes in visceral fat of metabolically unhealthy obese
      (MUO) individuals are significantly larger than those in metabolically healthy
      obese individuals. Since adipocyte size is positively correlated with adipocyte
      death, we propose that endogenous oils have a higher propensity to be released
      from hypertrophied visceral fat in MUO individuals and that this is the key
      factor in driving inflammation. In summary, this study shows that adipocytes
      contain a potent oil adjuvant which drives IL-1alpha-dependent proinflammatory
      responses in vivo.

PMID- 24458364
TI  - Application of marginal structural models in pharmacoepidemiologic studies: a
      systematic review.
AB  - PURPOSE: We systematically reviewed pharmacoepidemiologic studies published in
      2012 that used inverse probability weighted (IPW) estimation of marginal
      structural models (MSM) to estimate the effect from a time-varying treatment.
      METHODS: Potential studies were retrieved through a citation search within Web of
      Science and a keyword search within PubMed. Eligibility of retrieved studies was
      independently assessed by at least two reviewers. One reviewer performed data
      extraction, and a senior epidemiologist confirmed the extracted information for
      all eligible studies. RESULTS: Twenty pharmacoepidemiologic studies were eligible
      for data extraction. The majority of reviewed studies did not report whether the
      positivity assumption was checked. Six studies performed intention-to-treat
      analyses, but none of them reported adherence levels after treatment initiation.
      Eight studies chose an as-treated analytic strategy, but only one of them
      reported modeling the multiphase of treatment use. Almost all studies performing
      as-treated analyses chose the most recent treatment status as the functional form
      of exposure in the outcome model. Nearly half of the studies reported that the
      IPW estimate was substantially different from the estimate derived from a
      standard regression model. CONCLUSIONS: The use of IPW method to control for time
      varying confounding is increasing in medical literature. However, reporting of
      the application of the technique is variable and suboptimal. It may be prudent to
      develop best practices in reporting complex methods in epidemiologic research.

PMID- 24458366
TI  - Unusual hafnium-pyridylamido/ER(n) heterobimetallic adducts (ER(n) = ZnR2 or
      AlR3).
AB  - NMR spectroscopy and DFT studies indicate that the Symyx/Dow Hf(IV)-pyridylamido
      catalytic system for olefin polymerization, [{N(-),N,CNph(-)}HfMe][B(C6F5)4] (1,
      Nph = naphthyl), interacts with ER(n) (E = Al or Zn, R = alkyl group) to afford
      unusual heterobimetallic adducts [{N(-),N}HfMe(MU-CNph)(MU-R)ER(n-1)][B(C6F5)4 in
      which the cyclometalated Nph acts as a bridge between Hf and E. (1)H VT (variable
      temperature) EXSY NMR spectroscopy provides direct evidence of reversible alkyl
      exchanges in heterobimetallic adducts, with ZnR2 showing a higher tendency to
      participate in this exchange than AlR3. 1-Hexene/ERn competitive reactions with 1
      at 240 K reveal that the formation of adducts is strongly favored over 1-hexene
      polymerization. Nevertheless, a slight increase in the temperature (to >265 K)
      initiates 1-hexene polymerization.

PMID- 24458365
TI  - A vascular and thrombotic model of gastroschisis.
AB  - A binary vascular/thrombotic pathogenesis for gastroschisis, a form of congenital
      bowel herniation, is proposed, where normal right umbilical vein involution
      creates a possible site for thrombosis adjacent to the umbilical ring. If
      thrombosis occurs, it weakens the area, explaining overwhelmingly right-sided
      lesions. The model arises from the existence of two groups of risk factors with
      different maternal age associations. Older mothers show a greater association
      with vascular factors (although this may actually represent a lack of any
      significant maternal age effect), consistent with associations of gastroschisis
      with congenital heart lesions and with amyoplasia. Alternatively, other
      predispositions, and especially decreased maternal age, the greatest known risk
      factor, associate with factors raising maternal estrogen, with evidence that
      estrogen in turn acts here as a predisposition to thrombosis. Absorption of
      thrombotic by-products from the amniotic fluid can explain the unusual amniocyte
      inclusions that are common with gastroschisis, while a role for estrogens
      suggests a connection between rising gastroschisis prevalence and increasing
      environmental contamination with estrogen disruptors. This model explains a
      variety of structural and epidemiological findings, and suggests that
      stratification of data based on binary effects may clarify associated risks and
      mechanisms. The model also shows that what is often referred to as vascular
      disruption may actually reflect alternative or additional factors instead,
      including thrombosis as a primary mechanism.

PMID- 24458368
TI  - The association between organic school food policy and school food environment:
      results from an observational study in Danish schools.
AB  - AIMS: School food in many countries has become the object of change and
      innovation processes, not only in relation to policies for healthier eating but
      also in relation to policies for more sustainable food consumption and
      procurement. The purpose of this study was to examine the possible influence that
      organic food sourcing policies in Danish school meal systems may have on the
      development of healthier school food environments. METHODS: The study was a cross
      sectional analysis undertaken among 179 school food coordinators (SFCs) through a
      web-based questionnaire (WBQ) in a sample of Danish public primary schools. The
      'organic' schools were compared to 'non-organic' schools. The questionnaire
      explored the attitudes, intentions/policies and actions in relation to organic
      and healthy foods served in the schools. RESULTS: Data indicates that 20
      'organic' schools were associated with the indicators of healthier school
      environments, including adopting a Food and Nutrition Policy (FNP) in the school
      (p = .032), recommending children to eat healthily (p = .004). CONCLUSIONS: The
      study suggests that organic food policies in schools may have potential to
      support a healthier school food environment.

PMID- 24458369
TI  - Laboratory policies on reporting secondary findings in clinical whole exome
      sequencing: initial uptake of the ACMG's recommendations.

PMID- 24458367
TI  - In vitro activity of Carvacrol against titanium-adherent oral biofilms and
      planktonic cultures.
AB  - OBJECTIVE: The aim of this study was to test the effect of Carvacrol against oral
      pathogens and their preformed biofilms on titanium disc surface. METHODS: Minimum
      inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and
      biofilm inhibitory concentration (BIC) were performed to evaluate Carvacrol
      antibacterial activity, while flow cytometry (FCM) was used to verify the
      Carvacrol effect on esterase activity and membrane permeability. Carvacrol was
      tested in vitro on single- and multi-species biofilms formed on titanium disc by
      Streptococcus mutans ATCC 25175, Porphyromonas gingivalis ATCC 33277 or
      Fusobacterium nucleatum ATCC 25586, in different combinations, comparing its
      effect to that of chlorhexidine. RESULTS: The pathogens were sensitive to
      Carvacrol with MICs and MBCs values of 0.25 % and 0.50 % and BICs of 0.5 % for S.
      mutans ATCC 25175 and 1 % for P. gingivalis ATCC 33277 and F. nucleatum ATCC
      25586. FCM analysis showed that treatment of planktonic cultures with Carvacrol
      caused an increase of damaged cells and a decrement of bacteria with active
      esterase activity. Moreover, Carvacrol demonstrated greater biofilm formation
      preventive property compared to chlorhexidine against titanium-adherent single-
      and multi-specie biofilms, with statistically significant values. CONCLUSIONS:
      Carvacrol showed inhibitory activity against the tested oral pathogens and
      biofilm formation preventive property on their oral biofilm; then, it could be
      utilized to control and prevent the colonization of microorganisms with
      particular significance in human oral diseases. CLINICAL RELEVANCE: This natural
      compound may be proposed in daily hygiene formulations or as an alternative agent
      supporting traditional antimicrobial protocols to prevent periodontal diseases in
      implanted patients.

PMID- 24458370
TI  - Direct chemical conversion of graphene to boron- and nitrogen- and carbon
      containing atomic layers.
AB  - Graphene and hexagonal boron nitride are typical conductor and insulator,
      respectively, while their hybrids hexagonal boron carbonitride are promising as a
      semiconductor. Here we demonstrate a direct chemical conversion reaction, which
      systematically converts the hexagonal carbon lattice of graphene to boron
      nitride, making it possible to produce uniform boron nitride and boron
      carbonitride structures without disrupting the structural integrity of the
      original graphene templates. We synthesize high-quality atomic layer films with
      boron-, nitrogen- and carbon-containing atomic layers with full range of
      compositions. Using this approach, the electrical resistance, carrier mobilities
      and bandgaps of these atomic layers can be tuned from conductor to semiconductor
      to insulator. Combining this technique with lithography, local conversion could
      be realized at the nanometre scale, enabling the fabrication of in-plane atomic
      layer structures consisting of graphene, boron nitride and boron carbonitride.
      This is a step towards scalable synthesis of atomically thin two-dimensional
      integrated circuits. 

PMID- 24458373
TI  - Positive and negative factors that influence concussion reporting among secondary
      school athletes.
AB  - CLINICAL SCENARIO: Concussions are one of the most common sport-related injuries
      affecting athletes participating at all levels across a variety of sports. It has
      been reported that up to 3.8 million concussive events occur per year that are
      sports-related. One significant issue with identifying concussions is that a
      clinical diagnosis is based on the presence of signs and symptoms, which are self
      reported by the patient. In the adolescent population, injury to the brain is
      possible with even the slightest insult, which can affect recovery and predispose
      them to subsequent concussions. Recent legislative efforts have included athlete
      education as a means to improve concussion reporting. More specifically, all 50
      US states and the District of Columbia have implemented concussion legislation
      that includes some type of concussion education protocol, but there is still
      little evidence to suggest that enhanced knowledge levels result in behavior
      changes, including improved concussion-reporting practices. It is unclear what
      factors make an adolescent athlete more or less likely to report the symptoms of
      a concussion. FOCUSED CLINICAL QUESTION: What factors positively or negatively
      influence secondary school athletes' likelihood of reporting symptoms of sport
      related concussions?

PMID- 24458372
TI  - Late presenting, contained rupture of the superficial femoral artery following
      atherectomy and stenting: case report and literature review.
AB  - Excisional atherectomy alone or followed by stenting is considered an appropriate
      treatment strategy for patients with lifestyle-limiting claudication due to
      obstructive infra-inguinal peripheral arterial disease (Ramaiah et al., J
      Endovasc Ther 2006;13:592-6021). We present a case of a 69-year-old man with
      eccentric severely calcified disease of the superficial femoral artery (SFA)
      treated with excisional atherectomy followed by stenting with an interwoven
      nitinol stent. The procedure was complicated by extravascular stent migration
      associated with a contained rupture presenting 30 days after the intervention.
      The complication was successfully treated with a stent graft. Although rare,
      pseudoaneurysms have been reported at the site of prior atherectomy; however,
      this case is the first description of a contained rupture post atherectomy
      associated with erosion of a nitinol stent into an extra-luminal position. The
      mechanism and management of this complication are discussed.

PMID- 24458371
TI  - Altered proteostasis in aging and heat shock response in C. elegans revealed by
      analysis of the global and de novo synthesized proteome.
AB  - Protein misfolding and aggregation as a consequence of impaired protein
      homeostasis (proteostasis) not only characterizes numerous age-related diseases
      but also the aging process itself. Functionally related to the aging process are,
      among others, ribosomal proteins, suggesting an intimate link between
      proteostasis and aging. We determined by iTRAQ quantitative proteomic analysis in
      C. elegans how the proteome changes with age and in response to heat shock.
      Levels of ribosomal proteins and mitochondrial chaperones were decreased in aged
      animals, supporting the notion that proteostasis is altered during aging.
      Mitochondrial enzymes of the tricarboxylic acid cycle and the electron transport
      chain were also reduced, consistent with an age-associated energy impairment.
      Moreover, we observed an age-associated decline in the heat shock response. In
      order to determine how protein synthesis is altered in aging and in response to
      heat shock, we complemented our global analysis by determining the de novo
      proteome. For that, we established a novel method that enables both the
      visualization and identification of de novo synthesized proteins, by
      incorporating the non-canonical methionine analogue, azidohomoalanine (AHA), into
      the nascent polypeptides, followed by reacting the azide group of AHA by 'click
      chemistry' with an alkyne-labeled tag. Our analysis of AHA-tagged peptides
      demonstrated that the decreased abundance of, for example, ribosomal proteins in
      aged animals is not solely due to degradation but also reflects a relative
      decrease in their synthesis. Interestingly, although the net rate of protein
      synthesis is reduced in aged animals, our analyses indicate that the synthesis of
      certain proteins such as the vitellogenins increases with age. 

PMID- 24458374
TI  - Evaluation of commercial antibodies against human sphingosine-1-phosphate
      receptor 1.
AB  - Sphingosine-1-phosphate receptor 1 (S1P1), also called endothelial
      differentiation gene 1, plays an important role in migration, proliferation, and
      survival of several types of cells including endothelial cells and lymphocytes
      and is involved in multiple sclerosis. Two commercial rabbit anti-S1P1 antibodies
      (polyclonal and monoclonal) were tested on CHO cells expressing S1P1 receptors
      fused to the green fluorescent protein at the C-terminal end and on Pichia
      pastoris and HEK cells expressing cmyc-tagged S1P1. Polyclonal antibodies did not
      give any signal by Western blot, immunofluorescence, and flow cytofluorometry.
      Monoclonal antibodies were able to reveal an unspecific band by Western blot
      performed on various cell types. Consequently, in our hands and using our
      protocols, we show that these antibodies did not specifically detect S1P1
      receptors.

PMID- 24458375
TI  - Impact of increasing levels of advanced iterative reconstruction on image quality
      in low-dose cardiac CT angiography.
AB  - PURPOSE: To investigate the effects of an advanced iterative reconstruction (IR)
      technique on subjective and objective image quality (IQ) in low-dose cardiac CT
      angiography (CCTA). MATERIALS AND METHODS: 30 datasets of prospectively triggered
      "step-and-shoot" CCTA scans acquired on a 256-slice CT scanner with optimized
      exposure settings were processed on a prototype IR system using filtered back
      projection (FBP) and 4 levels of advanced IR (iDose4, Philips) providing
      incremental rates of IR (level 2, 4, 6, 7). In addition, the effects of different
      reconstruction kernels (semi-smooth [CB], standard with edge-enhancement [XCB])
      and a "multi-resolution" feature [MR] to preserve the noise power spectrum were
      evaluated resulting in a total of n = 480 image sets. Contrast-to-noise ratios
      (CNR) were computed from regions of interest at 9 coronary locations. The
      subjective IQ was rated on a 4-point-scale with "classic" image appearance and
      noise-related artifacts as main criteria. RESULTS: At an effective dose of 1.7 +/
      0.7 mSv, the CNR significantly improved with every increasing level of IR
      (range: 14.2 - 27.8; p < 0.001) with the best objective IQ at the highest level
      of IR (level 7). The subjective IQ, however, was rated best at the medium level
      of IR (level 4) with minimal artifacts and a more "classic" image appearance when
      compared to higher IR levels. The XCB kernel provided better subjective ratings
      than CB (p < 0.05) and the MR feature further increased the IQ at a high level of
      IR. CONCLUSION: The objective IQ of low-dose CCTA progressively improves with an
      increasing level of IR. The best subjective IQ, however, is reached at medium
      levels of IR combined with an edge-enhancing kernel allowing for preservation of
      a "classic" image appearance suggesting application in the clinical routine. KEY
      POINTS: * iterative reconstruction (IR) improves image quality in low-dose
      coronary CTA* objective image quality (CNR) enhances with increasing level of IR*
      best subjective image quality is reached at medium level of IR* "multi
      resolution" algorithm further improves image quality at a higher level of IR.

PMID- 24458376
TI  - Gelfoam for closure of large percutaneous transhepatic and transsplenic puncture
      tracts in pediatric patients.
AB  - PURPOSE: Evaluation of the efficacy and safety of Gelfoam for the closure of
      transhepatic or transsplenic parenchymal puncture tracts with large-bore sheaths
      in pediatric patients. MATERIALS AND METHODS: Between January 2012 and May 2013,
      8 percutaneous transhepatic accesses and 3 percutaneous transsplenic accesses
      were closed using percutaneous Gelfoam in pediatric patients. The primary study
      endpoints to determine treatment efficacy and safety were patient survival,
      technical success defined as successful closure of the puncture tract without
      signs of bleeding, and complication rates. The secondary study endpoints were the
      occurrence of local and systemic inflammation. RESULTS: Overall survival was 100
      % with a median follow-up of 256 days. The procedure was technically successful
      in 10 of 11 procedures. One patient suffered from bleeding, which was
      successfully managed by a single blood transfusion. No re-bleeding was detected
      during follow-up and no surgical interventions were necessary. No signs of local
      or systemic infections related to the Gelfoam application occurred. CONCLUSION:
      Percutaneous Gelfoam application is an effective and safe technique for the
      closure of transhepatic or transsplenic accesses in pediatric patients. KEY
      POINTS: Interventional closure of large transhepatic and transsplenic parenchymal
      accesses in children after interventional treatment is recommended to avoid
      bleeding. Gelfoam application does not cause artifacts in magnetic resonance
      imaging and does not increase the risk of local or systemic inflammation in
      comparison to permanent embolic agents. Thus, especially children under
      immunosuppressive therapy can benefit from the application of Gelfoam.

PMID- 24458377
TI  - Effect of kernels used for the reconstruction of MDCT datasets on the semi
      automated segmentation and volumetry of liver lesions.
AB  - PURPOSE: To evaluate the effect of different reconstruction kernels on the semi
      automated segmentation of liver lesions in MDCT. MATERIALS AND METHODS: A total
      62 liver lesions were measured by three independent radiologists with the semi
      automated segmentation software Oncology-Prototype (Fraunhofer MEVIS, Siemens
      Healthcare, Germany) using MDCT datasets (3-mm slice thickness, 2-mm increment)
      reconstructed with standard, soft and detailed kernels (Philips B, A and D). To
      ensure objective measurements, only lesions with satisfactory initial
      segmentation were included, and manual correction was not used. The effective
      diameter and volume were recorded for each lesion. Segmentation in the soft and
      detailed kernel datasets was performed by copying the initial seed's position
      from the standard kernel dataset. RESULTS: The mean effective lesion diameter was
      19.9 +/- 9.7 mm using the standard kernel. Comparing the three kernels, no
      significant differences were found. The mean difference was 1% +/- 6% for the
      standard kernel compared to the soft kernel, 3% +/- 13% for the standard kernel
      vs. the detailed kernel and 2% +/- 9% for the soft kernel compared to the
      detailed kernel. The intra-class correlation coefficients were > 0.96 in all
      cases. CONCLUSION: The semi-automated segmentation and volumetry of liver lesions
      shows reliable measurements regardless of the kernel used for reconstruction of
      the MDCT dataset. KEY POINTS: ? Semi-automated segmentation and volumetry of
      liver lesions is reliable regardless of the kernel used for reconstruction of the
      MDCT dataset. ? Until today the gold standard for the evaluation of tumor
      response has been unidimensional manual measurement. ? Volumetric measurements
      could improve the assessment of tumor growth.

PMID- 24458379
TI  - Editorial.

PMID- 24458378
TI  - Small RNAs in the Vibrionaceae: an ocean still to be explored.
AB  - In bacteria, the discovery of noncoding small RNAs (sRNAs) as modulators of gene
      expression in response to environmental signals has brought new insights into
      bacterial gene regulation, including control of pathogenicity. The Vibrionaceae
      constitute a family of marine bacteria of which many are responsible for
      infections affecting not only humans, such as Vibrio cholerae but also fish and
      marine invertebrates, representing the major cause of mortality in farmed marine
      species. They are able to colonize many habitats, existing as planktonic forms,
      in biofilms or associated with various hosts. This high adaptability is linked to
      their capacity to generate genetic diversity, in part through lateral gene
      transfer, but also by varying gene expression control. In the recent years,
      several major studies have illustrated the importance of small regulatory sRNAs
      in the Vibrionaceae for the control of pathogenicity and adaptation to
      environment and nutrient sources such as chitin, especially in V. cholerae and
      Vibrio harveyi. The existence of a complex regulatory network controlled by
      quorum sensing has been demonstrated in which sRNAs play central roles. This
      review covers major advances made in the discovery and elucidation of functions
      of Vibrionaceae sRNAs within the last 10 years.

PMID- 24458380
TI  - (15)N and inhibitor studies on the photorespiratory nitrogen cycle in maize
      leaves.
AB  - A combination of inhibitor and (15)N studies were used to investigate the
      photorespiratory nitrogen cycle in maize, a C4 plant. Inhibitors used included
      isonicotinyl hydrazide which blocks the conversion of glycine to serine,
      methionine sulfoximine an inhibitor of GS and azaserine an inhibitor of GOGAT.
      Results from levels of ammonia and amino acids and the distribution of (15)N into
      NH3, serine, glutamine and glutamate indicated that the photorespiratory N-cycle
      occurs in this C4 plant, but the rate of flux through this pathway is low as
      compared with that in C3 plants. 

PMID- 24458381
TI  - Succulence and CAM relationships in Aeonium genus.
AB  - The CAM has been tested in six species of the Aeonium genus by studying the
      diurnal fluctuation of organic acids, pH and night fixation of CO2. The existence
      of a mesophyll structure able to support this metabolism has been shown as well
      as a congruent periodicity in the pool of cell starch.We have calculated the S,
      ES and Sm indices in the six species. A series of regression equations of
      different grades and types were calculated and shown to have correlation
      coefficients statistically significant. This allows us to confirm the suitability
      of the Sm index as a rapid test to establish the CAM as postulated by former
      authors. 

PMID- 24458382
TI  - Effects of light quality on chlorophyll-forms Ca 684, Ca 690 and Ca 699 of the
      diatom Phaeodactylum tricornutum.
AB  - Colored light modifies the relative concentration of chlorophyll-forms of the
      diatom Phaeodactylum tricornutum compared to white-light control. No change in
      the ratio carotenoids/chlorophylls was observed after 4 days exposure to green
      light (max: 530 nm), blue light (max: 470 nm) or red light (lambda > 650 nm) of
      same intensity.However, the absorption spectra were modified, the content in Ca
      684, Ca 690, Ca 699 forms increased in red and green light cultures and
      photosynthetic unit size of PS II decreased by 30% in green and blue light
      cultures.Fluorescence emission and fluorescence excitation spectra according to
      the Butler and Kitajima method (1975) were carried out for each culture. Ca 669
      form was predominant in the two photosystems. The newly appeared far red forms
      fluoresce at 715 nm like PS I forms.We conclude that these new forms originated
      in a rearrangement of PS II forms. They do not transmit excitation energy to
      reaction center of PS I and are disconnected from the other chlorophyll-forms of
      the photosynthetic antennae. 

PMID- 24458383
TI  - Effects of water stress on the chlorophyll content, nitrogen level and
      photosynthesis of leaves of two maize genotypes.
AB  - The dynamics of leaf chlorophyll level, nitrogen content, photosynthesis and
      stomatal conductance were followed in detail in two cultivars of maize (Zea mays)
      during a short period of water stress, applied at tasseling, and during the
      subsequent recovery phase. Plants used in the experiment were grown in sand
      nutrient solution culture under field weather conditions. Water stress reduced
      chlorophyll levels, stomatal conductance and photosynthesis, but the nitrogen
      content of the leaves was not affected. It is concluded that the stress-induced
      loss of chlorophyll is not mediated by a lack of nitrogen. Considerable
      differences were observed between genotypes in the rate of post-stress recovery
      of chlorophyll level. Recovery, upon rewatering, of stomatal conductance and
      photosynthesis preceded that of chlorophyll level. Losses of up to 40% of leaf
      chlorophyll content were insufficient to affect rates of photosynthesis measured
      at mid-day. 

PMID- 24458384
TI  - Isolation and properties of membrane-bound cytochrome c-552 from photosynthetic
      bacterium Chromatium vinosum.
AB  - A membrane-bound cytochrome c-552 was isolated and purified from the
      photosynthetic bacterium Chromatium vinosum by treatment with sodium cholate,
      sodium deoxycholate and bacterial alkaline protease followed by gel
      filtration.The purified cytochrome c-552, which may have been modified by the
      protease treatment, was electrophoretically homogeneous. Its minimal molecular
      weight was estimated to be 19 and 20 kdaltons, respectively by SDS polyacrylamide
      gel electrophoresis and by gel filtration on Sephadex G-100.Cytochrome c-552
      showed the absorption maxima at 419, 523 and 552 nm in the reduced form. Reduced
      minus-oxidized difference millimolar absorption coefficient was 10.6 for the
      wavelength pair, 552 minus 540 nm. The midpoint potential at pH 8.0 was -130 mV.
      The polarity in the amino acid composition of cytochrome c-552 was 40.1% and
      reflected its hydrophobicity.The solubilized cytochrome c-552 was shown to be a
      different entity from the soluble flavocytochrome c-552 in several respects. 

PMID- 24458385
TI  - A new mechanism for adaptation to changes in light intensity and quality in the
      red alga, Porphyra perforata. II. Characteristics of state II-state III
      transitions.
AB  - Characteristics of state II-state III transitions in the red alga, Porphyra
      perforata, were studied by measuring the fluorescence time course at room
      temperature and fluorescence spectra at 77 K. The state II to III transition was
      induced by system II light and was sensitive to uncouplers of
      photophosphorylation. This state II to III transition has a dark step(s) that
      could be easily separated from the light process. A state III to II transition
      occurred in the dark, but system I light accelerated the transition. The
      accelerating effect of system I light was not sensitive to uncouplers of
      photophosphorylation, but was inhibited by the addition of valinomycin + KCl or
      antimycin A. Compared to state I-state II transitions, the state II-state III
      transitions occurred more rapidly. The state II to state III transitions are
      different from the state I to state II transitions in that in state III the
      activity of photosystem II is changed without having any effect on photosystem I
      activity (Satoh and Fork, Biochim. Biophys, Acta, in press, 1982). It is
      suggested that the state II-state III transition represents a mechanism by which
      the alga can avoid photodamage resulting from absorption of excess light energy
      by photosystem II. 

PMID- 24458386
TI  - Changes in the distribution of light energy between the two photosystems in
      spinach leaves.
AB  - Time courses of chlorophyll fluorescence at room temperature and fluorescence
      spectra at 77 K were measured to investigate the light-induced changes in the
      distribution of light energy between the two photosy stems in young spinach
      leaves. Illumination of the dark adapted leaves with primarily system II light
      induced typical fluorescence transients at room temperature. Fluorescence spectra
      at 77 K showed that the intensity of system II fluorescence at 77 K changed
      nearly in parallel with the fluorescence transients at room temperature within
      the range from M1 to T during illumination of the leaf.Illumination of the dark
      adapted leaves with light I produced an increase of system II fluorescence
      measured at 77 K. The characteristics of the changes induced by light I or II
      were different, showing that these two effects are related to different
      mechanisms.These results suggest that the dark state in spinach leaves is state
      II, that light I induces a state II to I transition, while light II induces
      fluorescence changes that are produced by mechanisms other than state I-state II
      transitions. 

PMID- 24458387
TI  - Photochemical reaction of chlorophyll biosynthesis at 4.2 K.
AB  - Phototransformation of protochlorophyllide in etiolated leaves was shown to take
      place at 4.2 K. Upon illumination of the sample a photoactive form PChlide650 was
      transformed into a non-fluorescent intermediate which was then transformed into
      fluorescent forms of chlorophyllide (Chlide) upon increase of temperature in the
      dark. Reported transformations are similar to those observed under illumination
      at 77 K. 

PMID- 24458388
TI  - Photosynthetic characteristics of leaves developed at different irradiances and
      temperatures: an extension of the current hypothesis.
AB  - Photosynthetic characteristics at high measurement irradiance were analyzed for
      single leaves of two C3 and one C4 species grown under twenty one combinations of
      irradiance level, irradiance duration, and air temperature in order to test the
      idea that photosynthetic characteristies developed by leaves in different
      environments are controlled by the daily amount of photosynthesis. Photosynthetic
      rates per unit area and mesophyll conductances at 25 degrees C and air levels of
      CO2 and O2, and parameters for two photosynthesis models were used to
      characterize the photosynthetic properties of the leaves. Leaves with highest
      values of the photosynthetic parameters for each species were often developed in
      environments with irradiance levels below saturation for photosynthesis, and with
      only 12 hours of irradiance per day. Lower air temperature during growth
      increased the photosynthetic characteristics for a given irradiance regime.
      Photosynthetic characteristics had higher correlation coefficients with daily
      photosynthesis of mature leaves divided by 24-hour leaf elongation rates of young
      leaves, than with daily photosynthesis alone, indicating that photosynthetic
      characteristics may be related to a balance between photosynthesis and leaf
      expansion. 

PMID- 24458389
TI  - Molecular structure and subcellular localization of spinach leaf glycolate
      oxidase.
AB  - Glycolate oxidase (E.C. 1.1.3.1) was purified from spinach leaves (Spinacia
      oleracea). The molecular weight of the native protein was determined by sucrose
      density gradient centrifugation to be 290,000 daltons (13S), whereas that of the
      monomeric form was 37,000 daltons. The quaternary structure of the holoenzyme is
      likely to be octameric, analogous to pumpkin cotyledon glycolate oxidase
      [Nishimura et al, 1982]. The subcellular localization of the enzyme was studied
      using linear sucrose density gradient centrifugation, and it was found that
      glycolate oxidase activity is detectable in both leaf peroxisomal and supernatant
      fractions, but not in chloroplasts and mitochondria; the activity distribution
      pattern is essentially similar to that for catalase, a known leaf peroxisomal
      enzyme. Ouchterlony double diffusion and immunotitration analyses, demontrated
      that the rabbit antiserum against purified spinach leaf glycolate oxidase cross
      reacted, identically, with the enzyme molecules present in two different
      subcellular fractions, i.e, the leaf peroxisome and supernatant fractions. It is
      thus concluded that the enzyme present in the supernatant is due to the
      disruption of leaf peroxisomes during the isolation, and hence glycolate oxidase
      is exclusively localized in leaf peroxisomes in spinach leaves. 

PMID- 24458390
TI  - The response to ribulose bisphosphate(4-) (RuBP (4-)) and RuBP-Mg (2-) in
      catalysis by structurally divergent RuBP carboxylase/oxygenases.
AB  - Free ribulose hisphosphate (RuBP(4-)) rather than its magnesium complex (RuBP
      Mg(2-)) was the apparent substrate for spinach ribulose bisphosphate
      carboxylase/oxygenase. The apparent Km for total RuBP (pH 8.0 at 30 degrees  C)
      increased with increasing Mg(2+) concentrations from 11.6 MUM at 13.33 mM Mg(2+)
      to 32.6 MUM at 40.33 mM Mg(2+). Similarly the apparent Km for RuBP-Mg(2-) complex
      increased with increasing Mg(2+) from 9.4 MUM at 13.33 mM Mg(2+) to 29.7 MUM at
      40.33 mM Mg(2+). However, the Km values for uncomplexed RuBP(4-) were independent
      of the (saturating) concentration of Mg(2+) (Km=2.2 MUM). The Vmax did not vary
      with the changing concentrations of Mg(2+).In contrast, the Km for total RuBP
      remained constant with varying Mg(2+) concentrations (Km=59.5 MUM) for the enzyme
      from R. rubrum. The apparent Km for the RuBP-Mg(2-) complex decreased with
      increasing Mg(2+) concentrations from 16.0 MUM at 7.5 mM Mg(2+) to 5.9 MUM at
      27.5 mM Mg(2+). The initial velocity for the C. vinosum enzyme was also found to
      be independent of the (saturating) concentration of Mg(2+) when total RuBP was
      varied in the assay. Thus the response to total RuBP by these two bacterial
      enzymes, which markedly differ in structure, was closely similar. 

PMID- 24458391
TI  - Conditions leading to precipitation of ribulose bisphosphate carboxylase
      oxygenase differ from those leading to enzyme activation.
AB  - The relation between conditions leading to precipitation and/or activation of Ru
      P2 carboxylase have been explored in order to test the hypothesis that
      conformational changes leading to precipitation might be identical to those which
      are presumed to lead to enzyme activation. From the results of kinetic and
      solubility studies, we conclude that this hypothesis is not valid, since changes
      in solubility of Ru-P2 carboxylase occur ten times as fast as changes in enzyme
      kinetics. 

PMID- 24458392
TI  - Reinvestigation of the chlorophyll distribution among the chlorophyll-proteins
      and chlorophyll-protein complexes of Hordeum vulgare L.
AB  - Solubilization of barley (Hordeum vulgare L.) thylakoid membranes with sodium
      dodecylsulphate plus sodium deoxycholate with or without Triton X-100 and
      subsequent fractionation in the polyacrylamide gel electrophoresis system
      described in this paper resulted: (1) in the resolution of the chlorophyll
      proteins and chlorophyll-protein complexes commonly known as CP1a, CP1, LHCP(1),
      LHCP(2), CPa and LHCP(3); (2) in the highly increased stability of CP1 and CP1a,
      as judged by their chlorophyll content, (3) at the expense of the free pigment
      concentration (4) which could be reduced to a negligible amount. Some 40% of the
      total chlorophyll contained in the mature higher plant thylakoid membrane is
      associated with CP1 and CP1 a and as already suggested before [19] no significant
      amount of free chlorophyll occurs in vivo. 

PMID- 24458393
TI  - The distribution of leaf photosynthetic activity in a mixed grass-legume pasture
      canopy.
AB  - The distribution of net photosynthetic activity of leaves was measured in a mixed
      grass (Setaria sphacelata var. sericea)-legume (Desmodium intortum) pasture stand
      using a method based on concurrent measurement of the rate of CO2 exchange, and
      (14)CO2 dosing followed by rapid harvesting according to height strata.
      Comparisons were also made between plots which differed in the period of regrowth
      following defoliation.The usual superiority of leaf net photosynthetic rates of a
      C4 grass, compared with C3 legume leaves, was found in the upper, well
      illuminated strata. These rates were, however, much lower than those usually
      described for horizontally exposed leaves, primarily because leaves in the
      pasture stand were inclined to the horizontal. At greater depth in the canopies,
      the superiority of rates in the grass was less evident, and consequently the
      relative contributions of grass and legume to canopy photosynthesis became more
      dependent on their leaf area indices.Attention is drawn to the relative
      simplicity of the method for examining the contribution of leaves, which may
      differ according to species or position in the canopy, to productivity of the
      whole stand. 

PMID- 24458394
TI  - RuBP carboxylase determination by enzymic estimation of D-3-PGA formed.
AB  - RuBPcarboxylase activity was measured in extracts of barley (Hordeum Vulgare L.,
      cv. HOP) seedlings both with the standard radiometric method and by measuring D-3
      phosphoglyceric acid formed enzymically in a two stage assay. In the different
      conditions used, characterized by different NaHCO3 concentrations, different pH
      and the presence and absence of oxygen, essentially the same ratio of D-3-PGA
      formed per (14)CO2 fixed was obtained. This ratio respected the known
      stoichiometry of two molecules of D-3-PGA formed per CO2 fixed.It is suggested
      that measurement of D-3-PGA enzymically in a two stage assay can be routinely
      used for the determination of RuBP case activity instead of the radiometric
      method. The advantages and the validity of the method are discussed. 

PMID- 24458395
TI  - Phosphoenolpyruvate carboxylase in Hydrilla plants with varying CO2 compensation
      points.
AB  - Incubation of the submersed aquatic macrophyte, Hydrilla vertieillata Royle, for
      up to 4 weeks in growth chambers under winter-like or summer-like conditions
      produced high (130 to 150 MUl CO2/l) and low (6 to 8 MUl CO2/l) CO2 compensation
      points (Gamma), respectively. The activities of both ribulose bisphosphate (RuBP)
      and phosphoenolpyruvate (PEP) carboxylases increased upon incubation but the
      major increase was in the activity of PEP carboxylase under the summer-like
      conditions. This reduced the ratio of RuBP/PEP carboxylases from 2.6 in high
      Gamma plants to 0.2 in low Gamma plants. These ratios resemble the values in
      terrestrial C3 and C4 species, respectively.Kinetic measurements of the PEP
      carboxylase activity in high and low Gamma plants indicated the Vmax was up to 3
      fold greater in the low Gamma plants. The Km (HCO3 (-)) values were 0.33 and 0.22
      mM for the high and low Gamma plants, respectively. The Km (PEP) values for the
      high and low Gamma plants were 0.23 and 0.40 mM, respectively; and PEP exhibited
      cooperative effects. Estimated Km (Mg(2+)) values were 0.10 and 0.22 mM for the
      high and low Gamma plants, respectively.Malate inhibited both PEP carboxylase
      types similarly. The enzyme from low Gamma plants was protected by malate from
      heat inactivation to a greater extent than the enzyme from high Gamma plants. The
      results indicated that C4 acid inhibition and protection were not reliable
      methods to distinguish C3 and C4 PEP carboxylases. The PEP carboxylase from low
      Gamma plants was inhibited more by NaCl than that from high Gamma plants. These
      analyses indicated that Hydrilla PEP carboxylases had intermediate
      characteristics between those of terrestrial C3 and C4 species with the low Gamma
      enzyme being different from the high Gamma enzyme, and closer to a C4 type. 

PMID- 24458396
TI  - Photosynthetic characteristics of Amaranthus tricolor, a C4 tropical leafy
      vegetable.
AB  - The gas exchange characteristics are reported for Amaranthus tricolor, a C4
      vegetable amaranth of southeastern Asia. Maximum photosynthetic capacity was
      48.3+/-1.0 MUmol CO2 m(-2) s(-1) and the temperature optimum was 35 degrees C.
      The calculated intercellular CO2 concentration at this leaf temperature and an
      incident photon flux (400-700 mm) of 2 mmol m(-2) s(-1) averaged 208+/-14 MUl l(
      1), abnormally high for a C4 species. The photosynthetic rate, intercellular CO2
      concentration, and leaf conductance all decreased with an increase in water vapor
      pressure deficit. However, the decrease in leaf conductance which resulted in a
      decrease in intercellular CO2 concentration accounted for only one fourth of the
      observed decrease in photosynthetic rate as water vapor pressure deficit was
      increased. Subsequent measurements indicated that the dependence of net
      photosynthesis on intercellular CO2 concentration changed with water vapor
      pressure deficit. 

PMID- 24458397
TI  - Ageing of chloroplasts in vitro - III. Comparison of the effects of ageing in
      vitro and senescence on the red absorption band and primary photochemical
      reactions of sunflower chloroplasts.
AB  - A comparison of changes in absorption properties and electron transport
      activities of chloroplasts ageing in vivo and in vitro is made. Chloroplasts from
      sunflower leaves senescing in vivo during 7 days in dark do not show a blue shift
      of the red absorption band; in contrast, the shift becomes apparent within 24 h
      of in vitro ageing of isolated organelles. Photosynthetic activity by
      chloroplasts is lost much faster during in vitro than in vivo ageing. During in
      vitro ageing, the rate of degradation of thylakoid membranes as characterised by
      the shift in the red absorption band and loss in Hill reaction is further
      accelerated in chloroplasts isolated from dark-induced senescing leaves,
      suggesting the influence of the in vivo status of the chloroplasts on their in
      vitro stability. 

PMID- 24458398
TI  - ATP-induced quenching of chlorophyll fluorescence in chloroplasts of higher
      plants. Dependence on structural properties of the membranes.
AB  - The ATP-induced quenching of chlorophyll fluorescence in chloroplasts of higher
      plants is shown to be inhibited when the mobility of the protein complexes into
      the thylakoid membranes is reduced. Its occurrence also requires the presence of
      LHC complexes and the ability of the membranes to unstack.These observations, in
      addition to a slight increase of charge density of the surface-as indicated by 9
      aminoacridine fluorescence and high salt-induced chlorophyll fluorescence studies
      and partial unstacking of the membranes-as monitored by digitonin method and 540
      nm light scattering changes-after phosphorylation, suggest that the ATP-induced
      quenching of chlorophyll fluorescence could reflect some lateral redistribution
      of membrane proteins in the lipid matrix of the thylakoids. 

PMID- 24458399
TI  - CAM-idling in Hoya carnosa (Asclepiadaceae).
AB  - In the leaf sueculent Asclepial Hoya carnosa (L.) R. Br., CAM photosynthesis
      occurred under well-watered conditions, as characterized by diurnal gas exchange
      and changes in titratable acidity. Following 10-12 days of severe water stress,
      the plants shifted from CAM to a modified CAM-idling mode of metabolism. CAM
      idling was characterized by complete or almost complete stomatal closure
      accompanied by CAM-like diurnal changes in titratable acidity. H. carnosa plants
      maintained this CAM-idling mode of photosynthesis for at least 8 weeks. Upon
      reirrigation, the plants returned to the original CAM mode within 1 week. These
      results suggested that CAM-idling is a reversible, intermediate form of sustained
      metabolism which enables plant survival under conditions of extended drought. 

PMID- 24458400
TI  - Chlorophyll a fluorescence transients: a fast data acquisition system to
      facilitate in vivo measurements.
AB  - Characteristics of primary phases in chlorophyll a fluorescence transients based
      on room temperature in vivo measurement with a Plant Productivity Fluorometer
      (Brancker Model SF-10) can be greatly facilitated by coupling the instrument to a
      fast data acquisition system. The SF-10 was linked to a Multitech Industrial
      Corporation Microprofessor Microcomputer and further modified to ensure
      simultaneous onset of light activation and signal capture. Circuit diagrams and
      program listings are given in detail.This microprocessor system is capable of
      capturing signal changes over a minimum period of 200 milliseconds to a maximum
      of 6 seconds. Accuracy of recorded data is dependent on rate of change of the
      input signal and the recording time period. Acquisition and storage of 5000
      points from zero to 300 milliseconds ensured clear resolution of Fo, I and D when
      played back over 120 seconds on a chart recorder. For routine use, the primary
      transient can be captured over 0-2 seconds and then replayed as an accompaniment
      to standard slower presentation of primary plus secondary transients. Coincidence
      of signal amplitude for Fp on both systems can then be ascertained while
      retaining adequate resolution of Fo and I. 

PMID- 24458402
TI  - Influence of methionine sulfoximine on the photosynthesis of isolated
      chloroplasts.
AB  - Methionine sulfoximine provided at a concentration which inhibits photosynthesis
      in intact leaves (10 mM) had no significant influence on the rate of
      photosynthesis of isolated pea leaf chloroplasts. In contrast, ammonium, 3-(3,4
      dichlorophenyl)-1,1-dimethylurea, and D,L-glyceraldehyde all strongly inhibited
      the photosynthesis of isolated chloroplasts. We conclude that low concentrations
      of methionine sulfoximine (up to 10 mM) have no direct effect on the
      photosynthetic process. 

PMID- 24458401
TI  - The action of lipase on chloroplast membranes: II. Polypeptide patterns of bean
      galactolipase- and phospholipase A2-treated thylakoid membranes.
AB  - Thylakoid membranes obtained from bean chloroplasts treated with bean
      galactolipase or phospholipase A2 (from Crotalus terr. terr.) showed marked
      changes in their polypeptide patterns when separated on SDS-PAGE. The obtained
      results have been discussed with regard to the relationship between chloroplast
      lipids and polypeptides originating from chlorophyll-protein complexes of bean
      thylakoids. A coexistence between galactolipids and the peripheral antennae in PS
      I complex and LHCP(3) as well as a conspicuous role of phospholipids in PSI and
      PSII centre chlorophyll-protein complexes has to be underlined. 

PMID- 24458403
TI  - The relationship between state II to state I transitions and cyclic electron flow
      around photosystem I.
AB  - The effects of electron acceptors, inhibitors of electron flow and uncouplers and
      inhibitors of photophosphorylation on a state II to I transition were studied. 3
      (3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) did not inhibit the state II to I
      transition. By contrast, 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB),
      methyl viologen and antimycin A inhibited the transition indicating that the
      cyclic electron flow around photosystem I, but not the oxidation of electron
      carriers (such as plastoquinone), induced the state II to I transition.
      Uncouplers, but not inhibitors of photophosphorylation, inhibited the state
      transition suggesting that the proton transport through the cyclic electron flow
      was related to the transition. 

PMID- 24458404
TI  - Temperature dependence of delayed ehlorophyll fluorescence in intact leaves of
      higher plants. A rapid method for detecting the phase transition of thylakoid
      membrane lipids.
AB  - The temperature dependence of the yield of in vivo prompt and delayed chiorophyll
      fluorescence was investigated in maize and barley leaves. In the chilling
      sensitive maize, delayed fluorescence at steady-state level showed a maximum near
      the temperature at which thylakoid membrane lipids undergo a phase transition as
      revealed by differential scanning calorimetry measurements. In the chilling
      resistant barley, no phase transition was detected above 0 degrees C and the
      delayed light emission varied in a monotonic fashion. It was shown that
      measurements of delayed luminescence intensity in vivo can provide a rapid and
      sensitive method for detecting the phase change of membrane lipids in intact
      leaves of chilling-sensitive plant species such as tomato, cotton, cucumber,
      castor bean or avocado. In contrast, the use of steady-state prompt chlorophyll
      fluorescence as an indicator of membrane fluidity change was not successful. 

PMID- 24458405
TI  - Estimation of protochlorophyll(ide) contents in plant extracts; re-evaluation of
      the molar absorption coefficient of protochlorophyll(ide).
AB  - In an attempt to solve the controversy about the evaluation of the molar
      absorption coefficient of PChl(ide), this coeffecient is estimated in this work
      by using an original experimental approach. The calculated molar absorption
      coefficient of PChl(ide) is 30.4.10(3) l mole(-1) cm(-1) at 626 nm in acetone
      80%; it is close to that derived from the specific absorption coefficient of
      Koski and Smith when assurning that the pigment extracted by these authors was
      the esterified pigment: PChl. Sets of equations for the quantification of
      Chl(ide) a, Chl b and PChl(ide) in 80% acetone extracts are derived. 

PMID- 24458406
TI  - Isolation and characterization of a 23 kDa protein essential for photosynthetic
      oxygen evolution.
AB  - A 23 kDa protein has recently been demonstrated to participate in photosynthetic
      oxygen evolution by reconstitution experiments on inside-out thylakoid vesicles
      (Akerlund H-E, Jansson C and Andersson B (1982) Biochim Biophys Acta 681:1-10).
      Here we describe the isolation of the 23 kDa protein from a spinach chloroplast
      extract using ion-exchange chromatography. The protein was obtained in a yield of
      25% and with less than 1% of contaminating proteins. The ability of the protein
      to stimulate oxygen evolution in inside-out thylakoids was preserved throughout
      the various fractionation steps. The isolated protein was highly water soluble
      and appeared as a monomer. Its isoelectric point was at pH=7.3. The amino acid
      composition showed a high content of polar amino acids, resulting in a polarity
      index of 49%. The isolated protein lacked metals and other prosthetic groups. Its
      function as a catalytic or regulating subunit in the oxygen evolving complex is
      discussed. 

PMID- 24458407
TI  - Isolation of intact chloroplasts with high CO2 fixation capacity from sugarbeet
      leaves containing calcium oxalate.
AB  - Intact chloroplasts were isolated from sugarbeet leaves by the mechanical
      disruption technique normally used for spinach. The chloroplast pellet contained
      a ring of white irregularly shaped crystals which were identified as calcium
      oxalate. The chloroplasts were greater than 90% intact yet good rates of CO2
      fixation were only obtained when inorganic pyrophosphate or 3-phosphoglycerate
      were added to the assay medium. Chloroplasts free of calcium oxalate were
      prepared by purification on a three step Percoll gradient. These purified
      chloroplasts were highly intact and showed high rates of CO2 fixation without
      adding inorganic pyrophosphate or 3-phosphoglycerate. With optimal assay
      conditions (0.2 mM orthophosphate and pH 8.0) rates of 110-130 MU mole per
      milligram chlorophyll per hour were routinely obtained. It is concluded that
      intact chloroplasts capable of high rates of CO2 fixation can be prepared from
      sugarbeet leaves using a simple three step Percoll gradient. 

PMID- 24458408
TI  - CO2 exchange of CAM exhibiting suceulents in the southern Namib desert in
      relation to microclimate and water stress.
AB  - The responses of CO2 exchange and overnight malate accumulation of leaf and stem
      succulent CAM-plants to water stress and the particular climatic conditiens of
      fog and fohn in the southern Namib desert have been investigated. In most of the
      investigated CAM plants a long term water stress gradually attenuated any uptake
      of external CO2 and led to CO2 release throughout day and night. No CAM-idling
      was observed. Rainfall or irrigation immediately restored daytime CO2 uptake
      while the recovery of the noctural CO2 uptake was delayed. Dawn peak of
      photosynthesis was only found in well watered plants but was markedly reduced by
      the short term water stress of a fohn-storm. Morning fog with its higher diffuse
      light intensity compared with clear days increased photosynthetic CO2 uptake
      considerably. Even in well watered plants noctural CO2 uptake and malate
      accumulation were strongly affected by fohn indicating that the water vapour
      pressure deficit during the night determines the degree of acidification. 

PMID- 24458410
TI  - Chlorophyll-protein-complexes of thylakoids of wild type and chlorophyll b
      mutants of Arabidopsis thaliana.
AB  - Pigment-protein-complexes of two chlorophyll b deficient mutants of Arabidopsis
      and from the wild type were separated electrophoretically. Light-harvesting
      proteins were absent in the chlorophyll b free mutant ch(1) and their amount was
      reduced in the mutant ch(2) which has a reduced content of chlorophyll b. The
      ratio of CPa:CP I increased with decreasing chlorophyll b content which indicated
      that the stoichiometry of photosystem II to photosystem I is not constant. 

PMID- 24458411
TI  - Net photosynthetic rate of sour cherry (Prunus cerasus L. 'Montmorency') during
      the growing season with particular reference to fruiting.
AB  - Diurnal and seasonal net photosynthetic rates (Pn) of sour cherry were
      determined. Leaf Pn was not significantly affected by shoot excision. Under
      constant environmental conditions (PFD, 1200 MUmol m(-2) s(-1); temp. 25;
      relative humidity, 80-90%) there was no significant diurnal fluctuation in Pn for
      individual leaves. However, there was a pronounced fluctuation in Pn for whole
      trees measured under constant temperature but natural variation in sunlight from
      sunrise to sunset. Maximum Pn occurred before solar noon, remained constant for 1
      2 hr, then declined. Photosynthetic rate of recently expanded leaves fluctuated
      through out the season but, in general, was greatest in the spring as leaves
      expanded, reached a peak, remained stable for several weeks, then gradually
      declined. The Pn of leaves on terminal shoots was not significantly different
      from the Pn of leaves on spurs of the same physiological age. The presence of
      fruit did not have a consistent effect on the Pn of sour cherry leaves. 

PMID- 24458412
TI  - Isolation of chlorophyll-protein complexes and quantification of electron
      transport components in Synura petersenil and Tribonema aequale.
AB  - The chlorophyll-protein complexes of the yellow alga Synura petersenii
      (Chrysophyceae) and the yellow-green alga Tribonema aequale (Xanthophyceae) were
      studied. The sodiumdodecylsulfate/sodiumdesoxycholate solubilized photosynthetic
      membranes of these species yielded three distinct pigment-protein complexes and a
      non-proteinous zone of free pigments, when subjected to SDS polyacrylamid gel
      electrophoresis. The slowest migrating protein was identical to complex I (CP I),
      the P-700 chlorophyll a-protein, which possessed 60 chlorophyll a molecules per
      reaction center in Tribonema and 108 in Synura. The zone of intermediate mobility
      contained chlorophyll a and carotenoids. The absorption spectrum of this complex
      was very similar to the chlorophyll a-protein of photosystem II (CP a), which is
      known from green plants. The fastest migrating pigment protein zone was
      identified as a light-harvesting chlorophyll-protein complex. In Synura this
      protein was characterized by the content of chlorophyll c and of fucoxanthin.
      Therefore this complex will be named as LH Chl a/c-fucocanthin protein. In
      addition to the separation of the chlorophyll-protein complexes the cellular
      contents of P-700, cytochrome f (bound cytochrome) and cytochrome c-553 (soluble
      cytochrome) were measured. The stoichiometry of cytochrome f: cytochrome c-553:P
      700 was found to be 1:4:2.4 in Tribonema and 1:6:3.4 in Synura. 

PMID- 24458413
TI  - Elevated atmospheric partial pressure of carbon dioxide and dry matter production
      of konjak (Amorphophallus konjac K. Koch).
AB  - Konjak (Amorphophallus konjac K. Koch) was grown under normal (350 MUbar) or
      enriched (700 MUbar) CO2 partial pressure in glasshouses kept at 33/26  degrees
      C. Doubling the CO2 partial pressure resulted in twice the yield of corm because
      the net CO2 assimilation rate doubled and, due to the simple source-sink
      relationship, the increased production was partitioned to the corm. The response
      to CO2 of assimilation by konjak is discussed in relation to its original habitat
      in the tropics. 

PMID- 24458414
TI  - Changes of the chlorophyll fluorescence induction kinetics of C3 and CAM plants
      during day/night cycles.
AB  - The induction kinetics of the 680 nm chlorophyll fluorescence were measured on
      attached leaves of Kalanchoe daigremontiana R. Hamet et Perr. (CAM plant), Sedum
      telephium L. and Sedum spectabile Bor. (C3 plant in spring, CAM plant in summer)
      and Raphanus sativus L. (C3 plant) at three different times during a 12/12 h
      day/night cycle. During the fluorescence transient the fluorescence intensity at
      the O, P and T-level (fO, fmax, fst,) was different for the plant species tested;
      this may be due to their different leaf structure, pigment composition and
      organization of their photosystems. The kinetics of the fluorescence induction
      depended on the time of preillumination or dark adaptation during the light/dark
      cycle but not on the type of primary CO2 fixation mechanism (C3 and CAM). For
      dark adapted leaves measured either at the end of the dark phase or after dark
      adaptation of plants taken from the light phase a higher P-level fluorescence, a
      higher variable fluorescence (P-O) and a larger complementary area were found
      than for leaves of plants taken directly from the light phase. This indicates the
      presence of largely oxidized photosystem 2 acceptor pools during darkness. During
      the light phase the fluorescence decline after the P-level was faster than during
      the dark phase; from this we conclude that the light adaptation of the
      photosynthetic apparatus (state 1->state 2 transition, Delta pH) during the
      induction period proceeded faster in plants taken from the light phase than in
      plants taken from the dark phase. 

PMID- 24458415
TI  - Photochemical activities and organization of photosynthetic apparatus of C3 and C
      4 plants grown under different light intensities.
AB  - Changes in the photochemical activities, influenced by variation in the growth
      light intensity, were followed in typical C3 (Phaseolus, Ipomoea) and C4
      (Amaranthus, Sorghum) plants. Progressive decrease in the growth light intensity
      accelerated the O-P fluorescence induction in whole leaves. Such acceleration of
      the fluorescence kinetics was found to be not due to enhanced photosystem II
      activity but possibly a result of reduced rate of electron flow between the two
      photosystems. This is supported by 4 lines of evidence: (1) by the Hill activity
      determined in the presence of electron acceptors functioning before and after
      plastoquinone; (2) the photosynthetic unit size determined after flash excitation
      showing variations that were apparently too small to account for the changes
      observed fluorescence induction; (3) modification of the kinetics of secondrange
      light-induced absorbance changes at 520 nm; and (4) absence of significant
      changes in the ratio of P700/total chlorophyll ratio.The P700/cytochrome f ratio,
      however, increased from the usual 1-1.5 to 3-4 in plants grown under 9% sunlight.
      Increase in the P700/cytochrome f ratio was found to be due to a decrease in the
      cytochrome f/chlorophyll ratio, and this was due to perhaps to a simultaneous
      increase in chlorophyll and decrease in cytochrome content. 

PMID- 24458416
TI  - Chlorophyll fluorescence yield changes as a tool in plant physiology I. The
      measuring system.

PMID- 24458418
TI  - Editorial note.

PMID- 24458417
TI  - A new evaluation of chlorophyll absorption in photosynthetic membranes.
AB  - The three major chlorophyll-proteins of spinach chloroplasts were solubilized
      with digitonin and isolated by electrophoresis with deoxycholate. The gel bands
      were identified from their absorption and fluorescence spectra measured at 77 K.
      The slowest moving band was a Photosystem I complex (CPI); the second, a
      Photosystem II complex (Cpa); and the third, a chlorophyll a-b, antenna complex
      (LHCP). When absorption spectra (630-730 nm) of the bands were added in the
      proportions found in the gel, the sum closely matched the absorption of the
      chloroplasts both before and after solubilization. Thus these spectra represent
      the native absorption of the major antenna chlorophyll-proteins of green plants.
      Each of these spectra was resolved with a computer assisted, curve-fitting
      program into 8 mixed Gaussian-Lorentzian shaped components. The major, Chl a
      components in the 3 fractions were different both in peak positions and
      bandwidths. This result suggests that each chlorophyll-protein has its own unique
      set of chlorophyll a spectral forms or components. 

PMID- 24458419
TI  - Water transport in plants: Mechanism of apparent changes in resistance during
      absorption.
AB  - Leaf water potentials were measured at various rates of water absorption in whole
      plants and detached leaves of well-watered Helianthus annuus L. The experiments
      were conducted in the steady state, where changes in leaf hydration did not
      affect the measurements but both the transpiration and growth components of
      absorption could be observed. Calculations of the total plant resistance to water
      transport showed that the resistance at low fluxes was about 30 times the
      resistance at high fluxes. Most of the change took place in the leaves, since
      similar changes could be demonstrated in detached leaves. The roots accounted for
      little of the change, since they varied in resistance by a factor of only 2.5 as
      flow varied.To ascertain whether the protoplasts of the leaves varied in
      resistance by an amount which could account for the change in resistance to water
      transport, measurements of rates of water movement in and out of the protoplasm
      were made when gradients in water potential between the protoplasts and the water
      source were varied. These showed that water movement did not occur at rates which
      could account for high rates of transpiration even when large differences in
      potential drove flow. The high temperature sensitivity of efflux confirmed that
      the leaf protoplasts limited flow in these experiments. When the edge of the leaf
      was excised and flow occurred primarily through the vascular system of the leaf,
      the resistance was much lower than in the protoplasts. It is therefore concluded
      that the leaf protoplasts represent a high resistance to water transport and that
      a considerable portion of the water involved in transpiration must bypass
      them.Calculations based on a model of water transport showed that the protoplast
      resistance was almost 30 times larger than the resistance of the path leading
      from the soil to the leaf protoplasts. The decrease in resistance of the leaves
      with increasing rates of absorption was therefore attributed to a decrease in
      water movement in and out of leaf cells, which involved a high resistance, and an
      increase in movement around the leaf protoplasts, which involved a low
      resistance. Since the experiments were conducted at the steady state, the high
      resistances were apparent at low rates of flow where only growth occurred,
      whereas the low resistances could be observed at high rates of flow because
      growth did not occur and flow consisted solely of transpiration. Because of the
      high resistance of the protoplast pathway, leaf water potentials were governed
      more by protoplast water movement than by transpiration over a considerable range
      of rates of water absorption. This may explain some of the differences in earlier
      work on leaf water potentials and water transport. 

PMID- 24458420
TI  - The role of gibberellin in hypocotyl extension of dark-growing Lupinus albus
      seedlings.
AB  - Six authentic gibberellins marginally promoted hypocotyl lengthening of etiolated
      lupin seedlings whereas extracted lupin "gibberellin-like" compounds were
      ineffective. However, dwarfing by AMO-1618 [2'-isopropyl-4'-(trimethyl-ammonium
      chloride)-5'-methylphenyl piperidine carboxylate] was totally counteracted by co
      application with GA3 and partially overcome by extracted lupin "gibberellins".
      Meaningful quantities of free extractable and diffusible gibberellins were
      detected; "bound" gibberellin activity was not found. The time-course of the
      decline in extractable gibberellin levels during the process of dwarfing showed a
      significant difference from 6 h after applying AMO-1618. It is suggested that
      axis growth is dependent on gibberellin in a system normally close to saturation
      for endogenous growth. 

PMID- 24458421
TI  - The roles of auxin and gibberellin in reversing radiation inhibition of hypocotyl
      lengthening.
AB  - Inhibition of hypocotyl lengthening in Lupinus albus seedlings mediated through
      the high energy reaction was not reversed by 5 authentic gibberellins nor by
      extracted lupin "gibberellin-like" compounds. However, inhibition by continuous
      light was largely overcome by applying IAA (indole-3-acetic acid) to intact
      seedlings. In contrast, inhibition of lengthening mediated through phytochrome in
      its low energy mode was reversed by gibberellin. It is concluded that light
      antagonises hormone-regulated growth. 

PMID- 24458422
TI  - The role of nuclear fusion in pollen embryogenesis of Datura innoxia Mill.
AB  - If anthers of Datura innoxia containing microspores are cultured at 28 degrees  C
      for 24 h, two forms of haploid pollen grains are produced; one with typical
      unequal generative and vegetative nuclei (A), and the other with equal
      vegetativetype nuclei (B). The A form predominates. After 24 to 72 h in culture,
      three embryogenic events ensue; 1) division of the vegetative cell in A grains
      accompanied by rapid degeneration of the generative cell, 2) simultaneous or
      independent mitosis of the nuclei in B grains, and 3) simultaneous mitosis of
      both the generative and vegetative nuclei in A grains following two successive
      cycles of DNA synthesis in the generative nucleus, but only one in the vegetative
      nucleus (C). The endoreduplicated generative nucleus gives rise to
      diplochromosomes which it is postulated divide on a common spindle together with
      the vegetative chromosomes to yield a 3n proembryoid. In other C grains,
      simultaneous mitosis of an endoreduplicated generative nucleus and two vegetative
      daughter nuclei can occur. Nuclear fusion in these grains is envisaged as leading
      to a 4n proembryoid. Diploid proembryoids probably arise by nuclear fusion in A
      or B grains. At plantlet emergence, mainly n and 2n plantlets are obtained.
      Higher ploidy proembryoids fail to develop probably as a result of competitive
      influences.Similar embryogenic events occur in cultures initiated at the stages
      of the first pollen mitosis and young pollen grains, but C embryogenesis
      predominates. Competition from lower ploidy embryoids is minimised and 3n, 4n and
      even 6n plantlets are obtained. 

PMID- 24458423
TI  - The role of reducing sugars in the geotropic response of the wheat node.
AB  - The distribution of sugars in the leaf sheath base of wheat (Triticum aestivum)
      becomes asymmetric following horizontal displacement, the reducing sugar content
      of the lower side rising to 300-400% of that of the upper side during a 24-h
      stimulation period. The changes involve the hydrolysis of sucrose and appear, in
      older organs, in the absence of growth. Although gravity-induced, the increase in
      reducing sugar content is not essential for initiation of the growth which gives
      rise to the geotropic response. 

PMID- 24458424
TI  - Katabolism of plant cytoplasmic ribosomes: RNA breakdown in senescent cotyledons
      of germinating broad-bean seedlings.
AB  - Broad-bean cotyledons lost about 80% of their RNA during the first 30 days of
      seed germination. Both high-molecular-weight ribosomal (r) RNA and low-molecular
      weight RNA were degraded at about the same rate. Only small quantities of
      breakdown products of rRNA were detected within senescent tissue. This finding
      contrasts strongly with the very rapid cleavage of rRNA and the accumulation of
      breakdown products when the same cotyledons were homogenised and then incubated
      at 25 degrees . It would appear, therefore, that there was a barrier between
      ribonuclease and most ribosomes in vivo which was disrupted by homogenisation.
      The results are discussed in relation to the mechanism of ribosome katabolism
      during senescence. 

PMID- 24458425
TI  - Katabolism of plant cytoplasmic ribosomes: A study of the interaction between
      ribosomes and ribonuclease.
AB  - Ribosome preparations from several species of flowering plant were found to
      contain ribonuclease. It was predominantly latent in ionic conditions which
      maintained the integrity of the ribosomes but was activated by agents which
      disrupted ribosome structure by chelating their divalent cations. The
      ribonuclease was not a structural component of the ribosomes but was
      preferentially adsorbed by them upon disruption of cells. Adsorption took place
      onto both large and small ribosomal subunits, and onto monosomes and polysomes.
      These results are discussed in relation to possible mechanisms for the breakdown
      of ribosomal RNA in vivo. 

PMID- 24458426
TI  - [Phytochrome-induced regeneration of adventitious roots in the mustard seedling
      (Sinapis alba L.)].
AB  - Isolated cotyledons and hypocotyl cuttings ("Restkeimlinge") taken from young (36
      h old) etiolated mustard seedlings at a stage of development at which nutrients
      are not yet limiting require active phytochrome (Pfr) to regenerate roots. The
      influence of photosynthesis on rooting (Lovell et al., 1969, 1972, 1973) appears
      to be limited to cotyledons depleted of storage materials. These conclusions are
      based on the following experimental results: 1. Continuous far-red irradiation
      ("Dauer-DR") is as effective as continuous red irradiation ("Dauer-HR") in
      stimulating rooting (Fig. 1). 2. Continuous far-red irradiation can be largely
      replaced by a series of 5 min red/12 h dark cycles. Five min far-red irradiations
      have no detectable effect if given alone, but fully reverse the action of red if
      given subsequently to the red irradiation (Fig. 3).Phytochrome-mediated rooting
      in mustard is limited to cuttings taken from seedlings not older than about 60 h
      under our experimental conditions (Fig. 2). However, rooting is stimulated by
      continuous far-red light not only in the case of irradiated cuttings but also in
      the case in which seedlings are irradiated before dissection and the cuttings
      subsequently kept in darkness (Fig. 4).-It appears from these data that Pfr
      increases the capacity for rooting in intact seedlings as well as in cuttings,
      but has no influence on the time-course of rooting set in motion by dissection.
      There is no evidence for a function of the plumule in the rooting response. It
      rather appears that phytochrome is needed to produce a hormonal rooting factor in
      the cotyledons. 

PMID- 24458427
TI  - Risk factors for treatment failure of CO2 laser vaporization in cervical
      intraepithelial neoplasia 2.
AB  - PURPOSE: The aim of our study was to evaluate the risk factors for treatment
      failure of CO2 laser vaporization in patients with cervical intraepithelial
      neoplasia 2 (CIN2). METHODS: Medical records of patients who received either
      shallow or deep CO2 laser vaporization with biopsy-proven CIN2 during March 2007
      to April 2011 were reviewed retrospectively. After laser vaporization, liquid
      based cytology and human papilloma virus (HPV) DNA testing were checked in every
      follow-up visit. Treatment failure was defined when the follow-up biopsy was more
      than CIN2, needing secondary surgical treatment. RESULTS: During that period, 141
      patients with CIN2 underwent CO2 laser vaporization. After laser ablation, 14 of
      141 women needed the secondary treatment, a success rate of laser vaporization of
      90.1 %. In multivariate analysis, the previous loop electrosurgical excision
      procedure (LEEP) history (adjusted OR = 13.649; P value = 0.025) and the ablation
      depth (adjusted OR = 11.279; P value = 0.006) were independent factors associated
      with treatment failure. CONCLUSION: Both ablation depth and previous LEEP history
      were the important factors increasing the risk for the treatment failure of CO2
      laser vaporization in CIN2.

PMID- 24458428
TI  - Biomaterial scaffolds for treating osteoporotic bone.
AB  - Healing fractures resulting from osteoporosis or cancer remains a significant
      clinical challenge. In these populations, healing is often impaired not only due
      to age and disease, but also by other therapeutic interventions such as
      radiation, steroids, and chemotherapy. Despite substantial improvements in the
      treatment of osteoporosis over the last few decades, osteoporotic fractures are
      still a major clinical challenge in the elderly population due to impaired
      healing. Similar fractures with impaired healing are also prevalent in cancer
      patients, especially those with tumor growing in bone. Treatment options for
      cancer patients are further complicated by the fact that bone anabolic therapies
      are contraindicated in patients with tumors. Therefore, many patients undergo
      surgery to repair the fracture, and bone grafts are often used to stabilize
      orthopedic implants and provide a scaffold for ingrowth of new bone. Both
      synthetic and naturally occurring biomaterials have been investigated as bone
      grafts for repair of osteoporotic fractures, including calcium phosphate bone
      cements, resorbable polymers, and allograft or autograft bone. In order to re
      establish normal bone repair, bone grafts have been augmented with anabolic
      agents, such as mesenchymal stem cells or recombinant human bone morphogenetic
      protein-2. These developing approaches to bone grafting are anticipated to
      improve the clinical management of osteoporotic and cancer-induced fractures. 

PMID- 24458429
TI  - Osteoblast-chondrocyte interactions in osteoarthritis.
AB  - There is now general agreement that osteoarthritis (OA) involves all structures
      in the affected joint, culminating in the degradation of the articular cartilage.
      It is appropriate to focus particularly on the subchondral bone because
      characteristic changes occur in this tissue with disease progression, either in
      parallel, or contributing to, the loss of cartilage volume and quality. Changes
      in both the articular cartilage and the subchondral bone are mediated by the
      cells in these two compartments, chondrocytes and cells of the osteoblast
      lineage, respectively, whose primary roles are to maintain the integrity and
      function of these tissues. In addition, altered rates of bone remodeling across
      the disease process are due to increased or decreased osteoclastic bone
      resorption. In the altered mechanical and biochemical environment of a
      progressively diseased joint, the cells function differently and show a different
      profile of gene expression, suggesting direct effects of these external
      influences. There is also ex vivo and in vitro evidence of chemical crosstalk
      between the cells in cartilage and subchondral bone, suggesting an
      interdependence of events in the two compartments and therefore indirect effects
      of, for example, altered loading of the joint. It is ultimately these cellular
      changes that explain the altered morphology of the cartilage and subchondral
      bone. With respect to crosstalk between the cells in cartilage and bone, there is
      evidence that small molecules can transit between these tissues. For larger
      molecules, such as inflammatory mediators, this is an intriguing possibility but
      remains to be demonstrated. The cellular changes during the progression of OA
      almost certainly need to be considered in a temporal and spatial manner, since it
      is important when and where observations are made in either human disease or
      animal models of OA. Until recently, comparisons have been made with the
      assumption, for example, that the subchondral bone is behaviorally uniform, but
      this is not the case in OA, where regional differences of the bone are evident
      using magnetic resonance imaging (MRI). Nevertheless, an appreciation of the
      altered cell function during the progression of OA will identify new disease
      modifying targets. If, indeed, the cartilage and subchondral bone behave as an
      interconnected functional unit, normalization of cell behavior in one compartment
      may have benefits in both tissues. 

PMID- 24458430
TI  - Recognition of Salmonella by Dectin-1 induces presentation of peptide antigen to
      type B T cells.
AB  - Type B T cells recognize peptide-MHC class II (pMHCII) isoforms that are
      structurally distinct from those recognized by conventional type A T cells. These
      alternative type B conformers result from peptide loading in the absence of HLA
      DM. Type A conformers are more stable than type B pMHCII conformers but bind the
      same peptide in the same register. Here, we show that interaction of Salmonella
      Typhimurium with bone marrow derived dendritic cells (BMDCs) isolated from
      C3H/HeNCr1 mice results in enhanced presentation of peptide Ag to type B T cells.
      The effect could be mimicked by purified PAMPs, the most potent of which were
      curdlan and zymosan, beta-(1,3)-glucan-containing polymers that are recognized by
      Dectin-1. Blocking of Dectin-1 with Ab and laminarin inhibited the induction of
      the type B T-cell response by BMDCs, confirming its role as a PRR for S.
      Typhimurium. Splenic DCs (sDCs) expressed Dectin-1 but were refractive to the
      induction of type B responses by S. Typhimurium and curdlan. Type B T cells have
      been shown to escape thymic tolerance and to transfer pathology in an autoimmune
      disease model. The induction of type B responses by gram-negative bacteria
      provides a mechanism by which autoreactive T cells may be produced during
      infection. 

PMID- 24458432
TI  - Sunlight adaptation region of Neanderthal genome found in up to 65% of modern
      East Asian populations.

PMID- 24458433
TI  - Duplication at Xq13.3-q21.1 with syndromic intellectual disability, a probable
      role for the ATRX gene.
AB  - Here we report on two unrelated male patients with syndromic intellectual
      disability (ID) due to duplication at Xq13.3-q21.1, a region of about 6 Mb and 25
      genes. Among these, the most outstanding is ATRX, the causative gene of X-linked
      alpha-thalassemia/mental retardation. ATRX belongs to the growing list of genes
      implied in chromatin remodeling causing ID. Many these genes, such as MECP2, are
      dose-sensitive so that not only deletions and point mutations, but also
      duplications cause ID. Both patients have severe ID, absent expressive speech,
      early hypotonia, behavior problems (hyperactivity, repetitive self-stimulatory
      behavior), postnatal growth deficiency, microcephaly, micrognathia,
      cryptorchidism, low-set, posteriorly angulated ears, and downslanting palpebral
      fissures. These findings are also usually present among patients with loss-of
      function mutations of the ATRX gene. Completely skewed X inactivation was
      observed in the only informative carrier mother, a constant finding among female
      carriers of inactivating point mutations of this gene. Participation of other
      duplicated genes cannot be excluded; nevertheless we propose that the increased
      dosage of ATRX is the major pathogenic mechanism of this X-linked disorder, a
      syndrome reminiscent of MECP2 duplication.

PMID- 24458431
TI  - Possible loss of the chloroplast genome in the parasitic flowering plant
      Rafflesia lagascae (Rafflesiaceae).
AB  - Rafflesia is a genus of holoparasitic plants endemic to Southeast Asia that has
      lost the ability to undertake photosynthesis. With short-read sequencing
      technology, we assembled a draft sequence of the mitochondrial genome of
      Rafflesia lagascae Blanco, a species endemic to the Philippine island of Luzon,
      with ~350* sequencing depth coverage. Using multiple approaches, however, we were
      only able to identify small fragments of plastid sequences at low coverage depth
      (<2*) and could not recover any substantial portion of a chloroplast genome. The
      gene fragments we identified included photosynthesis and energy production genes
      (atp, ndh, pet, psa, psb, rbcL), ribosomal RNA genes (rrn16, rrn23), ribosomal
      protein genes (rps7, rps11, rps16), transfer RNA genes, as well as matK, accD,
      ycf2, and multiple nongenic regions from the inverted repeats. None of the
      identified plastid gene sequences had intact reading frames. Phylogenetic
      analysis suggests that ~33% of these remnant plastid genes may have been
      horizontally transferred from the host plant genus Tetrastigma with the rest
      having ambiguous phylogenetic positions (<50% bootstrap support), except for psaB
      that was strongly allied with the plastid homolog in Nicotiana. Our inability to
      identify substantial plastid genome sequences from R. lagascae using multiple
      approaches--despite success in identifying and developing a draft assembly of the
      much larger mitochondrial genome--suggests that the parasitic plant genus
      Rafflesia may be the first plant group for which there is no recognizable plastid
      genome, or if present is found in cryptic form at very low levels.

PMID- 24458434
TI  - Iron-sulfur bond covalency from electronic structure calculations for classical
      iron-sulfur clusters.
AB  - The covalent character of iron-sulfur bonds is a fundamental electronic
      structural feature for understanding the electronic and magnetic properties and
      the reactivity of biological and biomimetic iron-sulfur clusters. Conceptually,
      bond covalency obtained from X-ray absorption spectroscopy (XAS) can be directly
      related to orbital compositions from electronic structure calculations, providing
      a standard for evaluation of density functional theoretical methods. Typically, a
      combination of functional and basis set that optimally reproduces experimental
      bond covalency is chosen, but its dependence on the population analysis method is
      often neglected, despite its important role in deriving theoretical bond
      covalency. In this study of iron tetrathiolates, and classical [2Fe-2S] and [4Fe
      4S] clusters with only thiolate ligands, we find that orbital compositions can
      vary significantly depending on whether they are derived from frontier orbitals,
      spin densities, or electron sharing indexes from "Atoms in Molecules" (AIM)
      theory. The benefits and limitations of Mulliken, Minimum Basis Set Mulliken,
      Natural, Coefficients-Squared, Hirshfeld, and AIM population analyses are
      described using ab initio wave function-based (QCISD) and experimental (S K-edge
      XAS) bond covalency. We find that the AIM theory coupled with a triple-zeta basis
      set and the hybrid functional B(5%HF)P86 gives the most reasonable electronic
      structure for the studied Fe-S clusters.

PMID- 24458435
TI  - A case of Rubinstein-Taybi syndrome and congenital neuroblastoma.

PMID- 24458436
TI  - Active von Willebrand factor predicts 28-day mortality in patients with systemic
      inflammatory response syndrome.
AB  - Endothelial dysfunction contributes to the pathology of systemic inflammatory
      response syndrome (SIRS). However, endothelial biomarkers are not routinely
      evaluated in this setting. Here, 275 patients with SIRS and plasma levels of von
      Willebrand factor (VWF), thrombospondin-1, myeloperoxidase, ADAMTS-13, and active
      VWF (aVWF) were studied in relation to 28-day mortality. On admission, aVWF
      levels were higher in nonsurvivors vs survivors (0.69 vs 0.47 ug/mL, P = .019).
      Patients in the highest tertile of aVWF levels had a lower cumulative survival
      (86% vs 75%, P = .017) and twofold increased hazard ratio (HR). When adjusted for
      the Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) score, this
      difference remained significant (HR 1.82, 95% confidence interval, 1.03-3.3). On
      admission, no significant differences were measured for the other proteins. These
      observations suggest that the stimulated release of VWF is not predictive for
      mortality in patients with SIRS, opposite of the processing of VWF after release.
      aVWF could be used with the APACHE-IV score to stratify SIRS patients at high
      mortality risk. 

PMID- 24458438
TI  - The cytokine midkine supports neutrophil trafficking during acute inflammation by
      promoting adhesion via beta2 integrins (CD11/CD18).
AB  - Emerging evidence suggests a role of the cytokine midkine (MK) in inflammation.
      In this study, its functional relevance for recruitment of polymorphonuclear
      neutrophils (PMNs) during acute inflammation was investigated. Intravital
      microscopy and histologic analysis of tumor necrosis factor-alpha-stimulated
      cremaster muscle venules revealed severely compromised leukocyte adhesion and
      extravasation in MK(-/-) mice compared with MK(+/+) animals. Systemic
      administration of recombinant MK completely rescued the adhesion defect in MK(-/
      ) mice. In a hind limb ischemia model, leukocyte accumulation in MK(-/-) mice was
      significantly diminished compared with MK(+/+) animals. However, MK did not lead
      to an inflammatory activation of PMNs or endothelial cells suggesting that it
      does not serve as classical proinflammatory cytokine. Unexpectedly, immobilized
      MK mediated PMN adhesion under static and flow conditions, whereas PMN-derived MK
      was dispensable for the induction of adhesion. Furthermore, adhesion
      strengthening remained unaffected by MK. Flow cytometry revealed that
      immobilized, but not soluble MK, significantly promoted the high affinity
      conformation of beta2 integrins of PMNs. Blocking studies of low-density
      lipoprotein receptor-related protein 1 (LRP1) suggested that LRP1 may act as a
      receptor for MK on PMNs. Thus, MK seems to support PMN adhesion by promoting the
      high affinity conformation of beta2 integrins, thereby facilitating PMN
      trafficking during acute inflammation. 

PMID- 24458437
TI  - Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell
      lymphoma: an Eastern Cooperative Oncology Group study (E1405).
AB  - Rituximab, bortezomib, modified hyper-cyclophosphamide, doxorubicin, vincristine,
      dexamethasone (VcR-CVAD) induction chemoimmunotherapy and maintenance rituximab
      (MR) were evaluated for efficacy and safety in Eastern Cooperative Oncology Group
      protocol E1405. Patients with previously untreated mantle cell lymphoma received
      VcR-CVAD chemotherapy every 21 days for 6 cycles, followed by MR for 2 years.
      Transplant-eligible patients had the option of autologous stem cell
      transplantation (ASCT) consolidation instead of MR. The primary end point was the
      complete response (CR) rate to VcR-CVAD. The secondary end points were overall
      response rate (ORR), progression-free survival (PFS), overall survival (OS), and
      toxicities. Seventy-five eligible patients with a median age of 62 (range 40-76)
      were enrolled. The ORR was 95% and a CR was achieved in 68% of patients. After a
      median follow-up of 4.5 years, 3-year PFS and OS were 72% and 88%, respectively.
      No substantial difference in PFS or OS was observed between patients treated with
      MR (n = 44) vs ASCT (n = 22). There were no unexpected toxicities. VcR-CVAD
      produced high ORR and CR rates in mantle cell lymphoma. MR after VcR-CVAD
      induction performed similarly to ASCT and may improve response duration.
      Randomized clinical trials comparing MR against ASCT should be considered and
      randomized clinical trials evaluating bortezomib's contribution to conventional
      therapy are under way. This study was registered at www.clinicaltrials.gov as
      #NCT00433537. 

PMID- 24458440
TI  - A return to a commonsense MI definition.

PMID- 24458439
TI  - Impact of mutational status on outcomes in myelofibrosis patients treated with
      ruxolitinib in the COMFORT-II study.
AB  - The JAK1/JAK2 inhibitor ruxolitinib produced significant reductions in
      splenomegaly and symptomatic burden and improved survival in patients with
      myelofibrosis (MF), irrespective of their JAK2 mutation status, in 2 phase III
      studies against placebo (COMFORT-I) and best available therapy (COMFORT-II). We
      performed a comprehensive mutation analysis to evaluate the impact of 14 MF
      associated mutations on clinical outcomes in 166 patients included in COMFORT-II.
      We found that responses in splenomegaly and symptoms, as well as the risk of
      developing ruxolitinib-associated anemia and thrombocytopenia, occurred at
      similar frequencies across different mutation profiles. Ruxolitinib improved
      survival independent of mutation profile and reduced the risk of death in
      patients harboring a set of prognostically detrimental mutations (ASXL1, EZH2,
      SRSF2, IDH1/2) with an hazard ratio of 0.57 (95% confidence interval: 0.30-1.08)
      vs best available therapy. These data indicate that clinical efficacy and
      survival improvement may occur across different molecular subsets of patients
      with MF treated with ruxolitinib. 

PMID- 24458441
TI  - The accuracy of the functional movement screen to identify individuals with an
      elevated risk of musculoskeletal injury.
AB  - CLINICAL SCENARIO: Injuries are somewhat commonplace in highly active
      populations. One strategy for reducing injuries is to identify individuals with
      an elevated injury risk before participation so that remediative interventions
      can be provided. Preparticipation screenings have traditionally entailed strength
      and flexibility measures thought to be indicative of inflated injury risk. Some
      researchers, however, have suggested that functional movements/tasks should be
      assessed to help identify individuals with a high risk of future injury. One
      assessment tool used for this purpose is the Functional Movement Screen (FMS).
      The FMS generates a numeric score based on performance attributes during 7
      dynamic tasks; this score is purported to reflect future injury risk. Expanding
      interest in the FMS has led researchers to investigate how accurately it can
      identify individuals with an increased risk of injury. FOCUSED CLINICAL QUESTION:
      Can the Functional Movement Screen accurately identify highly active individuals
      with an elevated risk of injury?

PMID- 24458442
TI  - Extended conjugated donor-acceptor molecules with E-(1,2-difluorovinyl) and
      diketopyrrolopyrrole (DPP) moieties toward high-performance ambipolar organic
      semiconductors.
AB  - Two diketopyrrolopyrrole (DPP)-based donor-acceptor (D-A) conjugated molecules,
      DPP-F and DPP-2F, which contain E-(1,2-difluorovinyl) moieties, are reported. The
      LUMO energies of DPP-F and DPP-2F were estimated to be -3.49 and -3.70 eV,
      respectively, based on their redox potentials and absorption spectral data; these
      values were clearly lowered because of the incorporation of electron-withdrawing
      E-(1,2-difluorovinyl) moieties. Organic field-effect transistors (OFETs) with
      thin films of DPP-F and DPP-2F were successfully fabricated with conventional
      techniques. Based on the respective transfer and output characteristics measured
      in an inert atmosphere, thin films of DPP-2F display ambipolar semiconducting
      behavior with hole and electron mobilities reaching 0.42 and 0.80 cm(2) V(-1) s(
      1), respectively. The as-prepared OFET of DPP-2F already shows high hole and
      electron mobilities that are not influenced remarkably by thermal annealing. For
      thin films of DPP-F, only p-type semiconducting behavior was observed in both an
      inert atmosphere and air, and the hole mobility increased to 0.1 cm(2) V(-1) s(
      1) after thermal annealing. XRD and AFM studies were performed with thin films of
      DPP-F and DPP-2F after annealing at different temperatures.

PMID- 24458444
TI  - From disilene (Si=Si) to phosphasilene (Si=P) and phosphacumulene (P=C=N).
AB  - The generation of heavier double-bond systems without by- or side-product
      formation is of considerable importance for their application in synthesis.
      Peripheral functional groups in such alkene homologues are promising in this
      regard owing to their inherent mobility. Depending on the steric demand of the N
      alkyl substituent R, the reaction of disilenide Ar2Si=Si(Ar)Li (Ar = 2,4,6
      iPr3C6H2) with ClP(NR2)2 either affords the phosphinodisilene Ar2
      Si=Si(Ar)P(NR2)2 (for R = iPr) or P-amino functionalized phosphasilenes
      Ar2(R2N)Si=Si(Ar)=P(NR2) (for R = Et, Me) by 1,3-migration of one of the amino
      groups. In case of R = Me, upon addition of one equivalent of tert
      butylisonitrile a second amino group shift occurs to yield the 1-aza-3
      phosphaallene Ar2(R2N)Si=Si(NR2)(Ar)-P=C=NtBu with pronounced ylidic character.
      All new compounds were fully characterized by multinuclear NMR spectroscopy as
      well as single-crystal X-ray diffraction and DFT calculations in selected cases.

PMID- 24458443
TI  - Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia
      patients and healthy controls: a placebo controlled crossover study.
AB  - RATIONALE: Residual effects of hypnotics on driving performance have been mainly
      determined in studies using a standardized driving test with healthy good
      sleepers. Responses to effects may differ, however, between insomniacs and
      healthy volunteers due to the underlying sleep disorder. In addition, a majority
      of insomniacs uses hypnotics chronically resulting in the development of
      tolerance to impairing effects. Impaired driving performance in healthy
      volunteers may then be an overestimation of the actual effects in insomniacs.
      OBJECTIVES: The present study aims to compare the residual effects of zopiclone
      7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs
      chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or
      infrequently using hypnotics (infrequent users), and 16 healthy, age matched,
      good sleepers (controls). METHODS: The study was conducted according to a 3 * 2
      double-blind, placebo controlled crossover design, with three groups and two
      treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and
      placebo administered at bedtime (2330 hours). Between 10 and 11 h after
      administration subjects performed a standardized highway driving test. RESULTS:
      Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both
      insomnia groups and healthy controls. The magnitude of impairment was
      significantly less in the chronic users group as compared with the controls.
      CONCLUSIONS: The smaller magnitude of effects suggests that investigating
      residual effects of hypnotics in healthy volunteers may yield a minor
      overestimation of the actual effects in insomnia patients.

PMID- 24458445
TI  - Photosynthetic characteristics of leaves developed at different irradiances and
      temperatures: an extension of the current hypothesis.
AB  - Photosynthetic characteristics at high measurement irradiance were analyzed for
      single leaves of two C3 and one C4 species grown under twenty one combinations of
      irradiance level, irradiance duration, and air temperature in order to test the
      idea that photosynthetic characteristics developed by leaves in different
      environments are controlled by the daily amount of photosynthesis. Photosynthetic
      rates per unit area and mesophyll conductances at 25 degrees C and air levels of
      CO2 and O2, and parameters for two photosynthesis models were used to
      characterize the photosynthetic properties of the leaves. Leaves with highest
      values of the photosynthetic parameters for each species were often developed in
      environments with irradiance levels below saturation for photosynthesis, and with
      only 12 hours of iradiance per day. Lower air temperature during growth increased
      the photosynthetic characteristics for a given irradiance regime. Photosynthetic
      characteristics had higher correlation coefficients with daily photosynthesis of
      mature leaves divided by 24-hour leaf elongation rates of young leaves, than with
      daily photosynthesis alone, indicating that photosynthetic characteristics may be
      related to a balance between photosynthesis and leaf expansion. 

PMID- 24458446
TI  - Molecular structure and subcellular localization of spinach leaf glycolate
      oxidase.
AB  - Glycolate oxidase (E.C. 1.1.3.1) was purified from spinach leaves (Spinacia
      oleracea). The molecular weight of the native protein was determined by sucrose
      density gradient centrifugation to be 290,000 daltons (13S), whereas that of the
      monomeric form was 37,000 daltons. The quaternary structure of the holoenzyme is
      likely to be octameric, analogous to pumpkin cotyledon glycolate oxidase
      [Nishimura et al, 1982]. The subcellular localization of the enzyme was studied
      using linear sucrose density gradient centrifugation, and it was found that
      glycolate oxidase activity is detectable in both leaf peroxisomal and supernatant
      fractions, but not in chloroplasts and mitochondria; the activity distribution
      pattern is essentially similar to that for catalase, a known leaf peroxisomal
      enzyme. Ouchterlony double diffusion and immunotitration analyses, demonstrated
      that the rabbit antiserum against purified spinach leaf glycolate oxidase cross
      reacted, identically, with the enzyme molecules present in two different
      subcellular fractions, i.e, the leaf peroxisome and supernatant fractions. It is
      thus concluded that the enzyme present in the supernatant is due to the
      disruption of leaf peroxisomes during the isolation, and hence glycolate oxidase
      is exclusively localized in leaf peroxisomes in spinach leaves. 

PMID- 24458447
TI  - The response to ribulose bisphosphate(4-) (RuBP (4-)) and RuBP-Mg (2-) in
      catalysis by structurally divergent RuBP carboxylase/oxygenases.
AB  - Free ribulose bisphosphate (RuBP(4-)) rather than its magnesium complex (RuBP
      Mg(2-)) was the apparent substrate for spinach ribulose bisphosphate
      carboxylase/oxygenase. The apparent Km for total RuBP (pH 8.0 at 30 degrees  C)
      increased with increasing Mg(2+) concentrations from 11.6 MUM at 13.33 mM Mg(2+)
      to 32.6 MUM at 40.33 mM Mg(2+). Similarly the apparent Km for RuBP-Mg(2-) complex
      increased with increasing Mg(2+) from 9.4 MUM at 13.33 mM Mg(2+) to 29.7 MUM at
      40.33 mM Mg(2+). However, the Km values for uncomplexed RuBP(4-) were independent
      of the (saturating) concentration of Mg(2+) (Km=2.2 MUM). The Vmax did not vary
      with the changing concentrations of Mg(2+).In contrast, the Km for total RuBP
      remained constant with varying Mg(2+) concentrations (Km=59.5 MUM) for the enzyme
      from R. rubrum. The apparent Km for the RuBP-Mg(2-) complex decreased with
      increasing Mg(2+) concentrations from 16.0 MUM at 7.5 mM Mg(2+) to 5.9 MUM at
      27.5 mM Mg(2+). The initial velocity for the C. vinosum enzyme was also found to
      be independent of the (saturating) concentration of Mg(2+) when total RuBP was
      varied in the assay. Thus the response to total RuBP by these two bacterial
      enzymes, which markedly differ in structure, was closely similar. 

PMID- 24458448
TI  - Conditions leading to precipitation of ribulose bisphosphate carboxylase
      oxygenase differ from those leading to enzyme activation.
AB  - The relation between conditions leading to precipitation and/or activation of Ru
      P2 carboxylase have been explored in order to test the hypothesis that
      conformational changes leading to precipitation might be identical to those which
      are presumed to lead to enzyme activation. From the results of kinetic and
      solubility studies, we conclude that this hypothesis is not valid, since changes
      in solubility of Ru-P2 carboxylase occur ten times as fast as changes in enzyme
      kinetics. 

PMID- 24458449
TI  - Reinvestigation of the chlorophyll distribution among the chlorophyll-proteins
      and chlorophyll-protein complexes of Hordeum vulgare L.
AB  - Solubilization of barley (Hordeum vulgare L.) thylakoid membranes with sodium
      dodecylsulphate plus sodium deoxycholate with or without Triton X-100 and
      subsequent fractionation in the polyacrylamide gel electrophoresis system
      described in this paper resulted: (1) in the resolution of the chlorophyll
      proteins and chlorophyll-protein complexes commonly known as CP1a, CP1, LHCP(1),
      LHCP(2), CPa and LHCP(3); (2) in the highly increased stability of CP1 and CP1a,
      as judged by their chlorophyll content, (3) at the expense of the free pigment
      concentration (4) which could be reduced to a negligible amount. Some 40% of the
      total chlorophyll contained in the mature higher plant thylakoid membrane is
      associated with CP1 and CP1a and as already suggested before [19] no significant
      amount of free chlorophyll occurs in vivo. 

PMID- 24458450
TI  - The distribution of leaf photosynthetic activity in a mixed grass-legume pasture
      canopy.
AB  - The distribution of net photosynthetic activity of leaves was measured in a mixed
      grass (Setaria sphacelata var. sericea)-legume (Desmodium intortum) pasture stand
      using a method based on concurrent measurement of the rate of CO2 exchange, and
      (14)CO2 dosing followed by rapid harvesting according to height strata.
      Comparisons were also made between plots which differed in the period of regrowth
      following defoliation.The usual superiority of leaf net photosynthetic rates of a
      C4 grass, compared with C3 legume leaves, was found in the upper, well
      illuminated strata. These rates were, however, much lower than those usually
      described for horizontally exposed leaves, primarily because leaves in the
      pasture stand were inclined to the horizontal. At greater depth in the canopies,
      the superiority of rates in the grass was less evident, and consequently the
      relative contributions of grass and legume to canopy photosynthesis became more
      dependent on their leaf area indices.Attention is drawn to the relative
      simplicity of the method for examining the contribution of leaves, which may
      differ according to species or position in the canopy, to productivity of the
      whole stand. 

PMID- 24458451
TI  - RuBP carboxylase determination by enzymic estimation of D-3-PGA formed.
AB  - RuBPcarboxylase activity was measured in extracts of barley (Hordeum Vulgare L.,
      cv. HOP) seedlings both with the standard radiometric method and by measuring D-3
      phosphoglyceric acid formed enzymically in a two stage assay. In the different
      conditions used, characterized by different NaHCO3 concentrations, different pH
      and the presence and absence of oxygen, essentially the same ratio of D-3-PGA
      formed per (14)CO2 fixed was obtained. This ratio respected the known
      stoichiometry of two molecules of D-3-PGA formed per CO2 fixed.It is suggested
      that measurement of D-3-PGA enzymically in a two stage assay can be routinely
      used for the determination of RuBP case activity instead of the radiometric
      method. The advantages and the validity of the method are discussed. 

PMID- 24458452
TI  - Phosphoenolpyruvate carboxylase in Hydrilla plants with varying CO2 compensation
      points.
AB  - Incubation of the submersed aquatic macrophyte, Hydrilla verticillata Royle, for
      up to 4 weeks in growth chambers under winter-like or summer-like conditions
      produced high (130 to 150 MUl CO2/1) and low (6 to 8 MUl CO2/l) CO2 compensation
      points (Gamma), respectively. The activities of both ribulose bisphosphate (RuBP)
      and phosphoenolpyruvate (PEP) carboxylases increased upon incubation but the
      major increase was in the activity of PEP carboxylase under the summer-like
      conditions. This reduced the ratio of RuBP/PEP carboxylases from 2.6 in high
      Gamma plants to 0.2 in low Gamma plants. These ratios resemble the values in
      terrestrial C3 and C4 species, respectively.Kinetic measurements of the PEP
      carboxylase activity in high and low Gamma plants indicated the Vmax was up to 3
      fold greater in the low Gamma plants. The Km (HCO3 (-)) values were 0.33 and 0.22
      mM for the high and low Gamma plants, respectively. The Km (PEP) values for the
      high and low Gamma plants were 0.23 and 0.40 mM, respectively; and PEP exhibited
      cooperative effects. Estimated Km (Mg(2+)) values were 0.10 and 0.22 mM for the
      high and low Gamma plants, respectively.Malate inhibited both PEP carboxylase
      types similarly. The enzyme from low Gamma plants was protected by malate from
      heat inactivation to a greater extent than the enzyme from high Gamma plants. The
      results indicated that C4 acid inhibition and protection were not reliable
      methods to distinguish C3 and C4 PEP carboxylases. The PEP carboxylase from low
      Gamma plants was inhibited more by NaCl than that from hight Gamma plants. These
      analyses indicated that Hydrilla PEP carboxylases had intermediate
      characteristics between those of terrestrial C3 and C4 species with the low Gamma
      enzyme being different from the high Gamma enzyme, and closer to a C4 type. 

PMID- 24458453
TI  - Photosynthetic characteristics of Amaranthus tricolor, a C4 tropical leafy
      vegetable.
AB  - The gas exchange characteristics are reported for Amaranthus tricolor, a C4
      vegetable amaranth of southeastern Asia. Maximum photosynthetic capacity was
      48.3+/-1.0MUmol CO2 m(-2)s(-1) and the temperature optimum was 35 degrees C. The
      calculated intercellular CO2 concentration at this leaf temperature and an
      incident photon flux (400-700 mm) of 2 mmol m(-2)s(-1) averaged 208+/-14 MUl l(
      1), abnormally high for a C4 species. The photosynthetic rate, intercellular CO2
      concentration, and leaf conductance all decreased with an increase in water vapor
      pressure deficit. However, the decrease in leaf conductance which resulted in a
      decrease in intercellular CO2 concentration accounted for only one fourth of the
      observed decrease in photosynthetic rate as water vapor pressure deficit was
      increased. Subsequent measurements indicated that the depence of net
      photosynthesis on intercellular CO2 concetration changed with water vapor
      pressure deficit. 

PMID- 24458454
TI  - Validation of patient-reported warfarin dose in a prospective incident cohort
      study.
AB  - PURPOSE: Inconsistencies in the definition and the collection of warfarin dosing
      data could lead to bias in observational, clinical, and pharmacogenetic studies.
      The present study aims to assess the concordance between patient-reported and
      prescribed warfarin doses among new warfarin users in the Quebec Warfarin Cohort
      (QWC) study. METHODS: Demographic, clinical, and lifestyle data were collected at
      cohort entry and each three months during a 1-year follow-up period among a
      subgroup of 219 patients from the prospective QWC study. We evaluated the
      differences between reported and prescribed warfarin doses overall and at each
      follow-up period. Concordance was tested in a multivariate generalized linear
      mixed model and allowed to vary from 95% to 105% of the prescribed dose. RESULTS:
      Overall, there was no significant difference between reported and prescribed
      warfarin doses (p>0.05, Pearson coefficient=0.969, power=100%). There was also no
      significant difference across each of four timepoints tested (p>0.05). We found
      that 84.0% of the reported warfarin doses were concordant with the prescribed
      doses. Having a history of myocardial infarction was significantly associated
      with a low concordance (OR=0.494; CI 95%: 0.286-0.852). CONCLUSION: In our
      population, we found that patient-reported warfarin dose and prescribed warfarin
      dose were comparable for the conduct of observational and clinical studies as
      well as for the validation and implementation of warfarin dosing algorithms.
      Moreover, the effect was similar whether measured in new-onset users of warfarin
      and after up to 12 months of use.

PMID- 24458455
TI  - The first europium(III) beta-diketonate complex functionalized polyhedral
      oligomeric silsesquioxane.
AB  - The first europium(III) beta-diketonate complex functionalized polyhedral
      oligomeric silsesquioxane (POSS) has been obtained by immobilization of such a
      complex at a silicon vertex of the POSS cage through the complexation of Eu(3+)
      ions with thenoyltrifluoroacetone-functionalized POSS. The new molecular hybrid
      material is liquid at room temperature, and shows bright-red emission when
      irradiated with UV light due to energy transfer from the thenoyltrifluoroacetone
      ligand to the coordinated Eu(3+) ions. Thermal analysis has revealed a
      significant improvement in the thermal stability of the material compared with
      tris(2-thenoyltrifluoroacetonate)europium(III) dihydrate, [Eu(TTA)3 ]?2 H2 O. In
      the context of recent advances in printable electronic technology, this novel
      luminescent organic liquid with the characteristic emission of Eu(3+) may
      potentially be useful in the development of next-generation organic devices such
      as flexible displays. 

PMID- 24458456
TI  - Public health guidance to facilitate timely diagnosis of dementia: ALzheimer's
      COoperative Valuation in Europe recommendations.
AB  - OBJECTIVE: ALzheimer's COoperative Valuation in Europe (ALCOVE) was a Joint
      Action co-financed by the European Commission to produce a set of evidence-based
      recommendations for policymakers on dementia. This paper reports on timely
      diagnosis. METHODS: Evidence was reviewed from scientific, policy and qualitative
      research. An online questionnaire was completed by experts from 24 European Union
      countries detailing current practice. An iterative process with people with
      dementia, family carers and professionals was utilised to develop
      recommendations. RESULTS: Advances in the technical aspects of diagnosis have
      changed what is understood by early diagnosis. Although research into preclinical
      stages is crucial, diagnosing at these very earliest stages is not recommended as
      regular practice. On balance, it is suggested that citizens should have access to
      accurate diagnosis at a time in the disease process when it can be of most
      benefit to them. The term timely diagnosis is used to reflect this. The diagnosis
      can help citizens and their families make sense of what is happening and make
      lifestyle changes and plans for the future. The central principles identified to
      maximise benefit and to reduce harm associated with diagnosis at an earlier stage
      included reducing stigma about dementia; respecting the rights of the individual;
      recognising that how the diagnosis is given will impact on subsequent adjustment
      and that post diagnostic support are required for the person and their family.
      Detailed recommendations are provided for timely detection, the diagnostic
      process, complex diagnoses, response to early cognitive changes and workforce.
      CONCLUSIONS: The recommendations can be utilised at a local, national and
      European level to benchmark progress.

PMID- 24458458
TI  - The role of key features in predator recognition by untrained birds.
AB  - The most important role in the recognition and categorization of predators (as
      well as other animals) is usually attributed to so-called key features. Under
      laboratory conditions, we tested the role of yellow eyes (specific for the genus
      Accipiter in European raptors) and hooked beak (common for all European birds of
      prey) in the recognition of the sparrowhawk (Accipiter nisus) by untrained great
      tits (Parus major) caught in the wild. Using wooden dummies, we interchanged
      either one of these potential key features or the body of the sparrowhawk
      (predator) and domestic pigeon (harmless bird). The tested tits showed three
      types of behaviour in the presence of the dummies: fear, interest without fear,
      and lack of interest. Eye interchange lowered fear of the sparrowhawk, but did
      not cause fear of the pigeon. Beak interchange did not lower fear of the
      sparrowhawk. Eye interchange caused increased interest in both species. Thus, a
      specific sparrowhawk feature is necessary for correct sparrowhawk dummy
      recognition but a general raptor feature is not. On the other hand, a specific
      sparrowhawk feature on a pigeon dummy is not enough to prompt sparrowhawk
      recognition. Thus, key features play an important, but not exclusive, role in
      predator recognition. An increased interest in some of the modified dummies
      implies that the tits have a general concept of a sparrowhawk. The individual
      variability in behaviour of tits is discussed. 

PMID- 24458459
TI  - Metabolic regulation in C4 photosynthesis: PEP-carboxylase and energy charge.
AB  - The effects of ATP, ADP and AMP on the activity of PEP carboxylase from
      Pennisetum purpureum (a C4 plant) have been investigated. AMP caused slight
      changes in activity. Both ATP and ADP were inhibitory. The extent of inhibition
      was related to the concentration of Mg(2+). Kinetics of inhibition (with PEP as
      variable substrate) were investigated at limiting concentrations of Mg(2+) (2
      mM); with excess Mg(2+) (5 mM); or with the concentration of Mg(2+) buffered at
      about 8 mM. At low Mg(2+) parabolic competitive-kinetics were observed. With
      higher Mg(2+) concentration linear competitive kinetics of inhibition were
      observed with a K i (slope) of 1.25 mM ATP. This was increased to 2.03 mM on
      addition of the allosteric activator glucose-6-P (5 mM). With Mg(2+) buffered ATP
      was an activator at low concentrations of PEP.Response to enegery charge was
      investigated using either calculated concentrations of all adenylates or mixtures
      of AMP and ATP pre-incubated with adenylate kinase. Inhibition at high charge
      could be reduced by increasing the concentration of Mg(2+) or by addition of the
      activator glucose-6-P. With enzyme-generated charge series and Mg(2+) buffered at
      8 mM an increase in activity was observed at high charge values.These results are
      discussed in terms of a possible regulatory role of adenylates in the C4
      dicarboxylic acid pathway of photosynthesis. 

PMID- 24458460
TI  - Detection and preliminary identification of endogenous antitranspirants in water
      stressed Sorghum plants.
AB  - Sorghum plants that had been subjected to different degrees of water stress were
      examined for the occurrence of endogenous compounds capable of inducing stomatal
      closure, i.e. "antitranspirants". Acidic extracts contained increased amounts of
      abscisic acid (ABA) as the amount of stress increased, but another highly active
      compound easily distinguished from ABA also accumulated. This compound, also
      found in neutral extracts, was probably all trans-farnesol, an isoprenoid alcohol
      which, like ABA, is a sesquiterpenoid. Highly dilute solutions of "commercial"
      farnesol induced stomatal closure when applied to isolated epidermis of
      Commelina. 

PMID- 24458461
TI  - Phloem transport in Ricinus: Concentration gradients between source and sink.
AB  - Solute concentration gradients were studied in Ricinus communis L. stems using
      refractometry linked with cryoscopic measurements of osmotic pressure. Techniques
      were developed to study the local composition of sieve-tube sap, effectively
      isolating bark segments by ring-massage or massage-girdling. In intact plants
      concentration gradients in stems were found to be steep near leaves, as reported
      previously, and also near roots. However, when transport from these organs was
      prevented, the steep gradients disappeared. Apparently they are caused by sap
      influx from nearby organs into stems during sampling. Concentration gradients in
      stems proper were almost negligible under standard growing conditions. They
      became positive (more concentrated above) when photosynthesis was enhanced, and
      negative in darkness.During exudation, leaves could secrete abundant concentrated
      sap for long periods. Stems had a similar but more limited capacity to secrete
      and, to a still lesser extent, roots also. Secretion was triggered even from
      natural sinks by exudation from an incision. Release from turgor pressure seems
      responsible rather than dilution of the phloem sap, suggesting that in whole
      plants a sink induces secretion and pressure-flow from distant sources by
      regulating the pressure within sieve tubes. The rate of exudation decreased as
      sap concentration fell, indicating that a reduction in pressure corresponds to
      assimilate exhaustion.The hydraulic conductivity of bark was not high, but was
      greater when the bark was secreting solutes. A change in mass-flow conduction
      between sieve tubes and storage cells is proposed to explain these differences in
      water permeability.The common assumption that solute concentration gradients
      correspond to pressure gradients seems inapplicable to whole Ricinus plants.
      Solute transfer can exceed the water flux so that osmotic equilibrium may not be
      reached at a particular location. In intact plants, solute gradients probably
      reflect source and sink activity with the interconnecting sieve tubes behaving
      rather passively, like pipes with a solute exchange-capacity. Actual pressure
      differences in sieve tubes are best indicated by sap concentration differences
      between source and sink. In Ricinus plants 0.5-1 m tall these pressures can be 5
      10 bar. 

PMID- 24458462
TI  - Localisation of adenosine triphosphatase activity in mature sieve elements of
      Tetragonia.
AB  - In the mature phloem of Tetragonia expansa strong ATPase activity is present on
      the plasmalemma of the companion cells and sieve tubes, and probably on the ER of
      the latter. The sieve tube wall sometimes shows a lead deposit. When the tissues
      is pre-treated with DNP there is often a diffuse deposit also on the P-protein
      and on the fibrillar protein from ruptured plastids. This is believed to be a
      diffusion artefact, and not to represent genuine P-protein activity. 

PMID- 24458463
TI  - [Auxin-ethylene interactions in the thigmotropic response of Cucumber tendrils].
AB  - Coiling of intact or excised cucumber (Cucumis sativus) tendrils can be induced
      by IAA or ethylene. The velocity of coiling in different regions of the tendrils
      correlates with the capacity for auxin-stimulated ethylene synthesis. Ethylene
      (Ethephon) induces an increase in membrane permeability of tendrils, and as a
      result the efflux of substances previously taken up (glucose) is stimulated. It
      is assumed that this may contribute to the contraction of the ventral side of the
      tendril. The excretion of glucose after ethylene treatment can be reduced by
      Ca(2+), and calcium also inhibits coiling of tendrils following incubation in
      ethephon solution. Auxin stimulated ethylene synthesis in the ventral half of the
      tendril is several times higher than in the dorsal half and it is hypothesized
      that this may be a cause for the different reactions of the two sides of a
      tendril following a mechanical stimulus. 

PMID- 24458464
TI  - [Influence of pH on uptake and release of sodium by Chlorella].
AB  - The Na metabolism of Chlorella fusca at high pH values was investigated by
      radiotracer methods. The Na influx into Chlorella is strongly (20-30 fold)
      enhanced in 5.10(-3)M NaOH (pH 11,4). It then approaches the rate of the influx
      of K (labelled with (86)Rb). The rise of the Na influx begins at pH 8.3 and has a
      point of inflection at pH 8.7. The cells remain undamaged.Na uptake from 5.10(
      3)M NaOH leads to a steady state with a 10-fold Na accumulation. The cells then
      contain 20-30 times more Na than in a neutral medium. The Na efflux remains
      proportional to the Na concentration in the cell. The Na uptake at high pH is
      energy-dependent, has saturation kinetics (K M =2.10(-3) mol/l) and is
      competitively inhibited by K. During Na uptake at high pH an equal amount of K is
      released from the cells. It is assumed that the enhancement of Na influx in NaOH
      is due to the fact that the selectivity for K of the membrane-bound K transport
      system is lowered under the alkaline conditions. Possibly an SH group is involved
      in this alteration.Neutralisation after Na accumulation from NaOH is followed by
      energy-dependent net Na efflux. An active Na efflux pump with first order
      kinetics is postulated. This pump can exchange Na against K and H. It is
      stimulated by external K, but can work without it. 

PMID- 24458465
TI  - Lignified sieve elements in the wheat leaf.
AB  - Sieve elements with thick, lignified walls are identified in the longitudinal
      bundles of the wheat leaf and appear to be functional. They are also present in
      several festucoid grasses but appear to be absent from the panicoid grasses
      examined. 

PMID- 24458466
TI  - Cytoplasmic microtubules in a yeast.
AB  - Electron micrographs showing cytoplasmic microtubules in the fission yeast
      Schizosaccharomyces pombe are described. The microtubules are found closely
      apposed to the microtubule organizing centre on the nuclear membrane and to
      mitochondria. 

PMID- 24458467
TI  - Photodormant lettuce seeds: Phytochrome-induced protein and lipid degradation.
AB  - Photodormant lettuce (Lactuca sativa L.) seeds were incubated in mannitol to
      prevent germination. Under these conditions, red light induced an extensive
      degradation of protein and a moderate one of lipid in the cortical cells of the
      radicle 24 h after treatment. It is suggested that the previously reported
      phytochrome-caused lowering of the water potential in light-treated embryos,
      which enables these embryos to overcome the resistance of the surrounding layers
      of the seed, is caused by lowering of the osmotic potential due to degradation of
      storage compounds in the radicle. 

PMID- 24458468
TI  - Differential reactivity of the red-and far-red-absorbing forms of phytochrome to
      [(14)C] N-ethyl maleimide.
AB  - The red-absorbing form (P r ) and the far-red absorbing form (P fr ) of
      undergraded, high-molecular-weight phytochrome from rye (Secale cereale L.)
      seedlings were examined for their reactivity toward N-ethyl-[(14)C]maleimide
      ([(14)C]-NEM). After pre-treatment of P r with cold NEM and extensive dialysis,
      photoconversion to P fr and treatment with [(14)C]NEM resulted in an
      approximately 70% increase in incorporation of radioactivity over the dark
      control. These results are discussed in relation to the view that phytochrome
      undergoes a protein conformational change upon phototransformation. 

PMID- 24458469
TI  - Altered cleavage patterns in human tripronuclear embryos and their association to
      fertilization method: a time-lapse study.
AB  - PURPOSE: To analyze the cleavage patterns in dipronuclear (2PN) and tripronuclear
      (3PN) embryos in relation to fertilization method. METHOD: Time-lapse analysis.
      RESULTS: Compared to 2PN, more 3PN IVF embryos displayed early cleavage into 3
      cells (p < 0.001), displayed longer duration of the 3-cell stage (p < 0.001), and
      arrested development from the compaction stage and onwards (p < 0.001). For the
      IVF embryos, the 2nd and 3rd cleavage cycles were completed within the expected
      time frame. However, timing of the cell divisions within the cleavage cycles
      differed between the two groups. In contrast, the completion of the 1st, 2nd, and
      3rd cleavage cycle was delayed, but with a similar division pattern for 3PN ICSI
      compared with the 2PN ICSI embryos. 3PN, more often than 2PN ICSI embryos,
      displayed early cleavage into 3 cells (p = 0.03) and arrested development from
      the compaction stage and onwards (p = 0.001). More 3PN IVF than ICSI embryos
      displayed early cleavage into 3 cells (p < 0.001). CONCLUSIONS: This study
      reports differences in cleavage patterns between 2PN and 3PN embryos and for the
      first time demonstrates differences in the cleavage pattern between 3PN IVF and
      ICSI embryos.

PMID- 24458470
TI  - The relationship between tumour stroma percentage, the tumour microenvironment
      and survival in patients with primary operable colorectal cancer.
AB  - BACKGROUND: Tumour stroma percentage (TSP) has previously been reported to
      predict survival in patients with colorectal cancer (CRC); however, whether this
      is independent of other aspects of the tumour microenvironment is unknown. In the
      present study, the relationship between TSP, the tumour microenvironment and
      survival was examined in patients undergoing elective, curative CRC resection.
      PATIENTS AND METHODS: Patients undergoing resection at a single centre (1997
      2008) were identified from a prospective database. TSP was measured at the
      invasive margin and its association with cancer-specific survival (CSS) and
      clinicopathological characteristics examined. RESULTS: Three hundred and thirty
      one patients were included in the analysis. TSP was associated with CSS in
      patients with stage I-III disease [hazard ratio (HR) 1.84, 95% confidence
      interval (CI) 1.17-2.92, P = 0.009], independent of age, systemic inflammation, N
      stage, venous invasion and Klintrup-Makinen score. Furthermore, TSP was
      associated with reduced CSS in patients with node-negative disease (HR 2.14, 95%
      CI 1.01-4.54, P = 0.048) and those who received adjuvant chemotherapy (HR 2.83,
      95% CI 1.23-6.53, P = 0.015), independent of venous invasion and host
      inflammatory responses. TSP was associated with several adverse pathological
      characteristics, including advanced T and N stage. Furthermore, TSP was
      associated with an infiltrative invasive margin and inversely associated with
      necrosis. CONCLUSIONS: The TSP was a significant predictor of survival in
      patients undergoing elective, curative CRC resection, independent of adverse
      pathological characteristics and host inflammatory responses. In addition, TSP
      was strongly associated with local tumour growth and invasion.

PMID- 24458471
TI  - Reply to: prediction of benefit from chemotherapy in ER-positive/HER2-negative
      breast cancer.

PMID- 24458472
TI  - Clinical variables associated with PSA response to abiraterone acetate in
      patients with metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: Abiraterone acetate (abiraterone) prolongs overall survival (OS) in
      patients with metastatic castration-resistant prostate cancer (mCRPC). This
      study's objective was to retrospectively identify factors associated with
      prostate-specific antigen (PSA) response to abiraterone and validate them in an
      independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR),
      thought to be an indirect manifestation of tumor-promoting inflammation, may be
      associated with response to abiraterone. PATIENTS AND METHODS: All patients
      receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March
      2013 were reviewed. The primary end point was confirmed PSA response defined as
      PSA decline >=50% below baseline maintained for >=3 weeks. Potential factors
      associated with PSA response were analyzed using univariate and multivariable
      analyses to generate a score, which was then evaluated in an independent cohort
      from Royal Marsden (RM) NHS foundation. RESULTS: A confirmed PSA response was
      observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%
      50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate
      dehydrogenase, an NLR <= 5 and restricted metastatic spread to either bone or
      lymph nodes were each associated with PSA response. In multivariable analysis,
      only low NLR and restricted metastatic spread remained statistically significant.
      A score derived as the sum of these two categorical variables was associated with
      response to abiraterone (P = 0.007). Logistic regression analysis on an
      independent validation cohort of 245 patients verified that this score was
      associated with response to abiraterone (P = 0.003). It was also associated with
      OS in an exploratory analysis. CONCLUSIONS: A composite score of baseline NLR and
      extent of metastatic spread is associated with PSA response to abiraterone and
      OS. Our data may help understand the role of systemic inflammation in mCRPC and
      warrant further research.

PMID- 24458474
TI  - On-going clinical trials for elderly patients with a hematological malignancy:
      are we addressing the right end points?
AB  - BACKGROUND: Cancer societies and research cooperative groups worldwide have urged
      for the development of cancer trials that will address those outcome measures
      that are most relevant to older patients. We set out to determine the
      characteristics and study objectives of current clinical trials in hematological
      patients. METHOD: The United States National Institutes of Health clinical trial
      registry was searched on 1 July 2013, for currently recruiting phase I, II or III
      clinical trials in hematological malignancies. Trial characteristics and study
      objectives were extracted from the registry website. RESULTS: In the 1207
      clinical trials included in this overview, patient-centered outcome measures such
      as quality of life, health care utilization and functional capacity were only
      incorporated in a small number of trials (8%, 4% and 0.7% of trials,
      respectively). Even in trials developed exclusively for older patients, the
      primary focus lies on standard end points such as toxicity, efficacy and
      survival, while patient-centered outcome measures are included in less than one
      fifth of studies. CONCLUSION: Currently on-going clinical trials in hematological
      malignancies are unlikely to significantly improve our knowledge of the optimal
      treatment of older patients as those outcome measures that are of primary
      importance to this patient population are still included in only a minority of
      studies. As a scientific community, we cannot continue to simply acknowledge this
      issue, but must all participate in taking the necessary steps to enable the
      delivery of evidence-based, tailor-made and patient-focused cancer care to our
      rapidly growing elderly patient population.

PMID- 24458473
TI  - Treatment outcome with mTOR inhibitors for metastatic renal cell carcinoma with
      nonclear and sarcomatoid histologies.
AB  - BACKGROUND: The clinical trials that reported benefit of the rapalogs
      temsirolimus and everolimus in advanced renal cell carcinoma (RCC) were primarily
      conducted in patients with clear-cell histology (ccRCC). We assessed outcome with
      these mammalian target of rapamicin (mTOR) inhibitors in two subsets of kidney
      cancer: sarcomatoid variant ccRCC and nonclear-cell RCC. PATIENTS AND METHODS:
      Baseline clinical features, information on prior treatment, and histologic
      subtypes were collected for patients previously treated with rapalogs for
      metastatic RCC of either nonclear phenotype or ccRCC with sarcomatoid features.
      Outcome was assessed centrally by a dedicated research radiologist for
      determination of tumor response, progression-free survival (PFS), and overall
      survival (OS). RESULTS: Eighty-five patients received temsirolimus (n = 59) or
      everolimus (n = 26). Nonclear-cell phenotypes included papillary (n = 14),
      chromophobe (n = 9), collecting duct (n = 4), translocation-associated (n = 3),
      and unclassified (n = 32) RCC. Twenty-three patients had clear-cell histology
      with sarcomatoid features. The response rate in assessable patients (n = 82) was
      7% (all partial responses); 49% of patients achieved stable disease, and 44% had
      progressive disease as their best response. Tumor shrinkage was observed in 26
      patients (32%). Median PFS and OS were 2.9 and 8.7 months, respectively. Nine
      patients (11%) were treated for >=1 year, including cases of papillary (n = 3),
      chromophobe (n = 2), unclassified (n = 3) RCC, and ccRCC with sarcomatoid
      features (n = 1). No tumor shrinkages were observed for patients with collecting
      duct or translocation-associated RCC. CONCLUSIONS: A subset of patients with
      nonclear-cell and sarcomatoid variant ccRCC subtypes benefit from mTOR
      inhibitors, but most have poor outcome. Histologic subtype does not appear to be
      helpful in selecting patients for rapalog therapy. Future efforts should include
      the identification of predictive tissue biomarkers.

PMID- 24458476
TI  - Prevalence of Temporal Bone Fractures in Patients with Mandibular Fractures Using
      Multidetector-Row CT.
AB  - PURPOSE: Temporal bone fracture after mandibular trauma is thought to be rare,
      and its prevalence has not been reported in the literature. The purpose of this
      study was to investigate the prevalence of temporal bone fractures in patients
      with mandibular fractures and the relationship between temporal bone fractures
      and the mandibular fracture location using multidetector-row computed tomography
      (MDCT). METHODS: A prospective study was performed in 201 patients with
      mandibular fractures who underwent 64-MDCT scans. The mandibular fracture
      locations were classified as median, paramedian, angle, and condylar types.
      Statistical analysis for the relationship between prevalence of temporal bone
      fractures and mandibular fracture locations was performed using chi(2) test with
      Fisher's exact test. A P-value < 0.05 was considered statistically significant.
      RESULTS: The percentage of cases with temporal bone fracture was 3.0 % of all
      patients with mandibular fractures and 19.0 % of those with multiple mandibular
      fractures of paramedian and condylar type. There was a significant relationship
      between the incidence of temporal bone fracture and the paramedian- and condylar
      type mandibular fracture (P = 0.001). CONCLUSIONS: Multiple mandibular fractures
      of paramedian and condylar type may be a stronger indicator for temporal bone
      fractures. This study suggests that patients with mandibular fracture, especially
      the paramedian and condylar type, should be examined for coexisting temporal bone
      fracture using MDCT.

PMID- 24458477
TI  - Managing healthcare budgets in times of austerity: the role of program budgeting
      and marginal analysis.
AB  - Given limited resources, priority setting or choice making will remain a reality
      at all levels of publicly funded healthcare across countries for many years to
      come. The pressures may well be even more acute as the impact of the economic
      crisis of 2008 continues to play out but, even as economies begin to turn around,
      resources within healthcare will be limited, thus some form of rationing will be
      required. Over the last few decades, research on healthcare priority setting has
      focused on methods of implementation as well as on the development of approaches
      related to fairness and legitimacy and on more technical aspects of decision
      making including the use of multi-criteria decision analysis. Recently, research
      has led to better understanding of evaluating priority setting activity including
      defining 'success' and articulating key elements for high performance. This body
      of research, however, often goes untapped by those charged with making
      challenging decisions and as such, in line with prevailing public sector
      incentives, decisions are often reliant on historical allocation patterns and/or
      political negotiation. These archaic and ineffective approaches not only lead to
      poor decisions in terms of value for money but further do not reflect basic
      ethical conditions that can lead to fairness in the decision-making process. The
      purpose of this paper is to outline a comprehensive approach to priority setting
      and resource allocation that has been used in different contexts across
      countries. This will provide decision makers with a single point of access for a
      basic understanding of relevant tools when faced with having to make difficult
      decisions about what healthcare services to fund and what not to fund. The paper
      also addresses several key issues related to priority setting including how
      health technology assessments can be used, how performance can be improved at a
      practical level, and what ongoing resource management practice should look like.
      In terms of future research, one of the most important areas of priority setting
      that needs further attention is how best to engage public members. 

PMID- 24458479
TI  - Guided-inquiry laboratory experiments in the analytical chemistry laboratory
      curriculum.

PMID- 24458480
TI  - A sensitive immunosorbent bio-barcode assay based on real-time immuno-PCR for
      detecting 3,4,3',4'-tetrachlorobiphenyl.
AB  - A functionalized gold-nanoparticle bio-barcode assay, based on real-time immuno
      PCR (IPCR), was designed for the determination of 3,4,3',4'-tetrachlorobiphenyl
      (PCB77). 15 nm gold nanoparticles were synthesized, and modified with thiol
      capped DNA and goat anti-rabbit IgG. The nanoparticle probes were used to replace
      antibody-DNA conjugate in the IPCR, and were fixed on the PCR tube wall via the
      immune reaction. Real-time PCR was performed to quantify the DNA signal directly.
      Under optimized conditions, the new method was used to detect PCB77 with a
      linearity range from 5 pg L(-1) to 10 ng L(-1), and the limit of detection (LOD)
      was 1.72 pg L(-1). Real samples of Larimichthys polyactis, collected from the
      East China Sea, were analyzed. Recovery was from 82 % to 112 %, and the
      coefficient of variation (CV) was acceptable. The results were compared with GC
      ECD, revealing that the method would be acceptable for providing rapid, semi
      quantitative, and reliable test results for making environmental decisions. 

PMID- 24458478
TI  - The link between periodontal disease and rheumatoid arthritis: an updated review.
AB  - Porphyromonas gingivalis is a leading pathogen in chronic periodontitis, a
      disease process involving progressive destruction of the tissues that support the
      teeth. Recently, the organism has been reported to produce a unique bacterial
      enzyme, P. gingivalis peptidyl-arginine deiminase (PPAD), which has the ability
      to convert arginine residues in proteins to citrulline. Protein citrullination
      alters protein structure and function; hence, PPAD may be involved in
      deregulation of the host's signalling network and immune evasion. Further,
      accumulating evidence suggests a role for autoimmunity against citrullinated
      proteins in the development of rheumatoid arthritis (RA). As inflammatory
      conditions in the lungs of cigarette smokers contribute to the breakdown of
      immune tolerance to citrullinated epitopes, chronic exposure to citrullinated
      proteins at periodontitis sites may also predispose susceptible individuals to
      the development of autoantibodies and the initiation of RA. In this review, we
      discuss evidence that PPAD may represent a mechanistic link between periodontitis
      and RA, diseases that are known to be significantly associated at the
      epidemiological level. 

PMID- 24458481
TI  - A lipidomic platform establishment for structural identification of skin
      ceramides with non-hydroxyacyl chains.
AB  - The stratum corneum (SC) is the outermost layer of skin that functions as a
      barrier and protects against environmental influences and transepidermal water
      loss. Its unique morphology consists of keratin-enriched corneocytes embedded in
      a distinctive mixture of lipids containing mainly ceramides, free fatty acids,
      and cholesterol. Ceramides are sphingolipids consisting of sphingoid bases, which
      are linked to fatty acids by an amide bond. Typical sphingoid bases in the skin
      are composed of dihydrosphingosine (dS), sphingosine (S), phytosphingosine (P),
      and 6-hydroxysphingosine (H), and the fatty acid acyl chains are composed of non
      hydroxy fatty acid (N), alpha-hydroxy fatty acid (A), omega-hydroxy fatty acid
      (O), and esterified omega-hydroxy fatty acid (E). The 16 ceramide classes include
      several combinations of sphingoid bases and fatty acid acyl chains. Among them, N
      type ceramides are the most abundant in the SC. Mass spectrometry (MS)/MS
      analysis of N-type ceramides using chip-based direct infusion nanoelectrospray
      ion trap mass spectrometry generated the characteristic fragmentation pattern of
      both acyl and sphingoid units, which could be applied to structural
      identification of ceramides. Based on the MS/MS fragmentation patterns of N-type
      ceramides, comprehensive fragmentation schemes were proposed. In addition, mass
      fragmentation patterns, which are specific to the sphingoid backbone of N-type
      ceramides, were found in higher m/z regions of tandem mass spectra. These
      characteristic and general fragmentation patterns were used to identify N-type
      ceramides in human SC. Based on established MS/MS fragmentation patterns of N
      type ceramides, 52 ceramides (including different classes of NS, NdS, NP, and NH)
      were identified in human SC. The MS/MS fragmentation patterns of N-type ceramides
      were characterized by interpreting their product ion scan mass spectra. This
      information may be used to identify N-type ceramides in the SC of human, rat, and
      mouse skin. 

PMID- 24458482
TI  - Self-assembly of chiral propeller-like supermolecules with unusual "sergeants-and
      soldiers" and "majority-rules" effects.
AB  - Chiral amplification is an interesting phenomenon in supramolecular chemistry
      mainly observed in complicated systems in which cooperative effect dominate.
      Herein, chiral, supramolecular, propeller-like architectures have been
      constructed through coassembly of an achiral disk-shaped molecule and chiral
      amino acid derivatives driven by intermolecular hydrogen bonding. Both the
      "sergeants-and-soldiers" principle and "majority-rules" effect are applicable in
      these discrete four-component supermolecules, which are the simplest
      supramolecular system ever reported that exhibit chiral amplification. 

PMID- 24458483
TI  - Progesterone Threshold Determines Nucleolar Channel System Formation in Human
      Endometrium.
AB  - Nucleolar channel systems (NCSs), micron-sized organelles specific to nuclei of
      human endometrial epithelial cells (EECs), are robust markers of the midluteal
      phase under the apparent control of progesterone. To gain further insight into
      the role of progesterone in NCS formation, we quantitatively assessed their
      sensitivity to oral contraceptive pills (OCPs) using immunofluorescence-based
      detection of NCSs. Comparison of endometrial biopsies and serum progesterone
      levels on cycle day (CD) 10 and 20 (LH +6/7) of 6 naturally cycling women and 6
      OCP users demonstrated that OCPs interfered with NCS formation on CD20, their
      natural peak presence. Although this confirmed prior observation based on
      electron microscopic sampling, OCPs unexpectedly induced limited but distinct
      amounts of NCSs already on CD10, when they are never present in natural cycles.
      Thus, OCPs can cause secretory changes in the endometrium during the
      proliferative phase. In a novel finding, robust NCS formation on CD20 was
      dependent on a 4 ng/mL progesterone threshold but did not correlate linearly with
      serum progesterone levels. Given the threshold being close to that serving as
      evidence for ovulation, NCSs can serve as ovulation markers.

PMID- 24458484
TI  - Oxidative Stress in Maternal Blood and Placenta From Mild Diabetic Rats.
AB  - The aim of the present study was at evaluating the effects of oxidative stress in
      blood and placenta of mild diabetic Wistar rats. At birth, Wistar rats received
      citrate buffer (nondiabetic group, n = 15) and another group received
      streptozotocin (100 mg/kg, subcutaneous) to induce mild diabetes (diabetic, n =
      15). The glycemia of these pregnant adult female rats were evaluated at days 0,
      7, 14, and 21 of pregnancy, and at term pregnancy, the blood and placental
      samples were collected for oxidative stress measurements. The mild diabetes
      caused glycemia superior to 120 mg/dL during pregnancy, increased superoxide
      dismutase, glutathione peroxidase, glutathione reductase activities, and
      malondialdehyde levels in the blood, and catalase activity in the placenta. Thus,
      mild diabetes increased activities of antioxidant substances aiming at defending
      against the exacerbated oxidative stress but were not enough. The placenta also
      answered to diabetic milieu and increased antioxidant defense, showing that even
      a mild hyperglycemia was enough to cause placental and maternal blood changes.

PMID- 24458485
TI  - Histomorphometric Analysis and Markers of Endometrial Receptivity Embryonic
      Implantation in Women With Polycystic Ovary Syndrome During the Treatment With
      Progesterone.
AB  - Literature data indicate that the infertility in women with polycystic ovary
      syndrome (PCOS) is not only attributed to anovulation but also to endometrial
      dysfunction. Endometrial biopsies were performed in the proliferative and
      secretory phases of women with normal cycle and in women with PCOS before and
      after oral treatment with micronized progesterone. After the treatment, the
      endometrium of the women with PCOS exhibited a lower number of glands and thicker
      luminal epithelium compared to the normal women in the secretory phase. In
      addition, the PCOS group exhibited reduced integrin and MECA-79 immunoexpression
      during the secretory phase. The expression of E-cadherin was higher in the PCOS
      and the expression of intercellular adhesion molecule 1 was lower in PCOS, during
      the secretory and proliferative phases, respectively. Also, there is a negative
      correlation with MECA-79 and integrin expression and body mass index.
      Conventional doses of progesterone may not be enough to correct the changes of
      endometrial histomorphology and the receptive markers of PCOS-bearing women. The
      obesity may be a factor that interferes with this response.

PMID- 24458486
TI  - Lower myocardial infarction survival in UK than Sweden blamed on slow uptake of
      new treatments.

PMID- 24458487
TI  - A second family with autosomal recessive spondylometaphyseal dysplasia and early
      death.
AB  - We report on a consanguineous Lebanese family in which two sibs had pre- and post
      natal growth retardation, developmental delay, large anterior fontanel, prominent
      forehead, low-set ears, depressed nasal bridge, short nose, anteverted nares,
      increased nasal width, prominent abdomen, and short limbs. Radiographs disclosed
      the presence of wormian bones, platyspondyly, decreased interpedicular distance
      at the lumbar vertebrae, square iliac bones, horizontal acetabula, trident
      acetabula, hypoplastic ischia, partial agenesis of the sacrum, ribs with cupped
      ends, short long bones with abnormal modeling, slight widening of the distal
      femoral metaphyses, and delayed epiphyseal ossification. Both sibs had a severe
      cardiomegaly and died at around 24 months from a heart failure. Differential
      diagnosis suggests that this is a second family presenting a newly described
      early lethal chondrodysplasia first reported by [Megarbane et al. (2008); Am J
      Med Genet Part A 146A:2916-2919].

PMID- 24458488
TI  - Ageing of chloroplasts in vitro - III. Comparison of the effects of ageing in
      vitro and senescence on the red absorption band and primary photochemical
      reactions of sunflower chloroplasts.
AB  - A comparison of changes in absorption properties and electron transport
      activities of chloroplasts ageing in vivo and in vitro is made. Chloroplasts from
      sunflower leaves senescing in vivo during 7 days in dark do not show a blue shift
      of the red absorption band; in contrast, the shift becomes apparent within 24 h
      of in vitro ageing of isolated organelles. Photosynthetic activity by
      chloroplasts is lost much faster during in vitro than in vivo ageing. During in
      vitro ageing, the rate of degradation of thylakoid membranes as characterised by
      the shift in the red absorption band and loss in Hill reaction is further
      accelerated in chloroplasts isolated from dark-induced senescing leaves,
      suggesting the influence of the in vivo status of the chloroplasts on their in
      vitro stability. 

PMID- 24458489
TI  - ATP-induced quenching of chlorophyll fluorescence in chloroplasts of higher
      plants. Dependence on structural properties of the membranes.
AB  - The ATP-induced quenching of chlorophyll fluorescence in chloroplasts of higher
      plants is shown to be inhibited when the mobility of the protein complexes into
      the thylakoid membranes is reduced. Its occurrence also requires the presence of
      LHC complexes and the ability of the membranes to unstack.These observations, in
      addition to a slight increase of charge density of the surface-as indicated by 9
      aminoacridine fluorescence and high salt-induced chlorophyll fluorescence studies
      and partial unstacking of the membranes-as monitored by digitonin method and 540
      nm light scattering changes-after phosphorylation, suggest that the ATP-induced
      quenching of chlorophyll fluorescence could reflect some lateral redistribution
      of membrane proteins in the lipid matrix of the thylakoids. 

PMID- 24458490
TI  - CAM-idling in Hoya carnosa (Asclepiadaceae).
AB  - In the leaf succulent Asclepiad Hoya carnosa (L.) R. Br., CAM photosynthesis
      occurred under well-watered conditions, as characterized by diurnal gas exchange
      and changes in titratable acidity. Following 10-12 days of severe water stress,
      the plants shifted from CAM to a modified CAM-idling mode of metabolism. CAM
      idling was characterized by complete or almost complete stomatal closure
      accompanied by CAM-like diurnal changes in titratable acidity. H. carnosa plants
      maintained this CAM-idling mode of photosynthesis for at least 8 weeks. Upon
      reirrigation, the plants returned to the original CAM mode within 1 week. These
      results suggested that CAM-idling is a reversible, intermediate form of sustained
      metabolism which enables plant survival under conditions of extended drought. 

PMID- 24458491
TI  - Chlorophyll a fluorescence transients: a fast data acquisition system to
      facilitate in vivo measurements.
AB  - Characteristics of primary phases in chlorophyll a fluorescence transients based
      on room temperature in vivo measurement with a Plant Productivity Fluorometer
      (Brancker Model SF-10) can be greatly facilitated by coupling the instrument to a
      fast data acquisition system. The SF-10 was linked to a Multitech Industrial
      Corporation Microprofessor Microcomputer and further modified to ensure
      simultaneous onset of light activation and signal capture. Circuit diagrams and
      program listings are given in detail.This microprocessor system is capable of
      capturing signal changes over a minimum period of 200 milliseconds to a maximum
      of 6 seconds. Accuracy of recorded data is dependent on rate of change of the
      input signal and the recording time period. Acquisition and storage of 5000
      points from zero to 300 milliseconds ensured clear resolution of Fo, I and D when
      played back over 120 seconds on a chart recorder. For routine use, the primary
      transient can be captured over 0-2 seconds and then replayed as an accompaniment
      to standard slower presentation of primary plus secondary transients. Coincidence
      of signal amplitude for Fp on both systems can then be ascertained while
      retaining adequate resolution of Fo and I. 

PMID- 24458492
TI  - The action of lipase on chloroplast membranes: II. Polypeptide patterns of bean
      galactolipase- and phospholipase A2-treated thylakoid membranes.
AB  - Thylakoid membranes obtained from bean chloroplasts treated with bean
      galactolipase or phospholipase A2 (from Crotalus terr. terr.) showed marked
      changes in their polypeptide patterns when separated on SDS-PAGE. The obtained
      results have been discussed with regard to the relationship between chloroplast
      lipids and polypeptides originating from chlorophyll-protein complexes of bean
      thylakoids. A coexistence between galactolipids and the peripheral antennae in PS
      I complex and LHCP(3) as well as a conspicuous role of phospholipids in PSI and
      PSII centre chlorophyll-protein complexes has to be underlined. 

PMID- 24458493
TI  - Influence of Methionine sulfoximine on the photosynthesis of isolated
      chloroplasts.
AB  - Methionine sulfoximine provided at a concentration which inhibits photosynthesis
      in intact leaves (10 mM) had no significant influence on the rate of
      photosynthesis of isolated pea leaf chloroplasts. In contrast, ammonium, 3-(3,4
      dichlorophenyl)-1,1-dimethylurea, and D,L-glyceraldehyde all strongly inhibited
      the photosynthesis of isolated chloroplasts. We conclude that low concentrations
      of methionine sulfoximine (up to 10 mM) have no direct effect on the
      photosynthetic process. 

PMID- 24458494
TI  - The relationship between state II to state I transitions and cyclic electron flow
      around photosystem I.
AB  - The effects of electron acceptors, inhibitors of electron flow and uncouplers and
      inhibitors of photophosphorylation on a state II to I transition were studied. 3
      (3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) did not inhibit the state II to I
      transition. By contrast, 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB),
      methyl viologen and antimycin A inhibited the transition indicating that the
      cyclic electron flow around photosystem I, but not the oxidation of electron
      carriers (such as plastoquinone), induced the state II to I transition.
      Uncouplers, but not inhibitors of photophosphorylation, inhibited the state
      transition suggesting that the proton transport through the cyclic electron flow
      was related to the transition. 

PMID- 24458495
TI  - Temperature dependence of delayed chlorophyll fluorescence in intact leaves of
      higher plants. A rapid method for detecting the phase transition of thylakoid
      membrane lipids.
AB  - The temperature dependence of the yield of in vivo prompt and delayed chlorophyll
      fluorescence was investigated in maize and barley leaves. In the chilling
      sensitive maize, delayed fluorescence at steady-state level showed a maximum near
      the temperature at which thylakoid membrane lipids undergo a phase transition as
      revealed by differential scanning calorimetry measurements. In the chilling
      resistant barley, no phase transition was detected above 0 degrees C and the
      delayed light emission varied in a monotonic fashion. It was shown that
      measurements of delayed luminescence intensity in vivo can provide a rapid and
      sensitive method for detecting the phase change of membrane lipids in intact
      leaves of chilling-sensitive plant species such as tomato, cotton, cucumber,
      castor bean or avocado. In contrast, the use of steady-state prompt chlorophyll
      fluorescence as an indicator of membrane fluidity change was not successful. 

PMID- 24458496
TI  - Estimation of protochlorophyll(ide) contents in plant extracts; re-evaluation of
      the molar absorption coefficient of protochlorophyll(ide).
AB  - In an attempt to solve the controversy about the evaluation of the molar
      absorption coefficient of PChl(ide), this coefficient is estimated in this work
      by using an original experimental approach. The calculated molar absorption
      coefficient of PChl(ide) is 30.4.10(3) 1 mole(-1) cm(-1) at 626 nm in acetone
      80%; it is close to that derived from the specific absorption coefficient of
      Koski and Smith when assuming that the pigment extracted by these authors was the
      esterified pigment: PChl. Sets of equations for the quantification of Chl(ide) a,
      Chl b and PChl(ide) in 80% acetone extracts are derived. 

PMID- 24458497
TI  - Isolation and characterization of a 23 kDa protein essential for photosynthetic
      oxygen evolution.
AB  - A 23 kDa protein has recently been demonstrated to participate in photosynthetic
      oxygen evolution by reconstitution experiments on inside-out thylakoid vesicles
      (Akerlund H-E, Jansson C and Andersson B (1982) Biochim Biophys Acta 681:1-10).
      Here we describe the isolation of the 23 kDa protein from a spinach chloroplast
      extract using ion-exchange chromatography. The protein was obtained in a yield of
      25% and with less than 1% of contaminating proteins. The ability of the protein
      to stimulate oxygen evolution in inside-out thylakoids was preserved throughout
      the various fractionation steps. The isolated protein was highly water soluble
      and appeared as a monomer. Its isoelectric point was at pH=7.3. The amino acid
      composition showed a high content of polar amino acids, resulting in a polarity
      index of 49%. The isolated protein lacked metals and other prosthetic groups. Its
      function as a catalytic or regulating subunit in the oxygen evolving complex is
      discussed. 

PMID- 24458498
TI  - Isolation of intact chloroplasts with high CO2 fixation capacity from sugarbeet
      leaves containing calcium oxalate.
AB  - Intact chloroplasts were isolated from sugarbeet leaves by the mechanical
      disruption technique normally used for spinach. The chloroplast pellet contained
      a ring of white irregularly shaped crystals which were identified as calcium
      oxalate. The chloroplasts were greater than 90% intact yet good rates of CO2
      fixation were only obtained when inorganic pyrophosphate or 3-phosphoglycerate
      were added to the assay medium. Chloroplasts free of calcium oxalate were
      prepared by purification on a three step Percoll gradient. These purified
      chloroplasts were highly intact and showed high rates of CO2 fixation without
      adding inorganic pyrophosphate or 3-phosphoglycerate. With optimal assay
      conditions (0.2 mM orthophosphate and pH 8.0) rates of 110-130 MU mole per
      milligram chlorophyll per hour were routinely obtained. It is concluded that
      intact chloroplasts capable of high rates of CO2 fixation can be prepared from
      sugarbeet leaves using a simple three step Percoll gradient. 

PMID- 24458499
TI  - CO2 exchange of CAM exhibiting succulents in the southern Namib desert in
      relation to microclimate and water stress.
AB  - The responses of CO2 exchange and overnight malate accumulation of leaf and stem
      succulent CAM-plants to water stress and the particular climatic conditions of
      fog and fohn in the southern Namib desert have been investigated. In most of the
      investigated CAM plants a long term water stress gradually attenuated any uptake
      of external CO2 and led to CO2 release throughout day and night. No CAM-idling
      was observed. Rainfall or irrigation immediately restored daytime CO2 uptake
      while the recovery of the nocturnal CO2 uptake was delayed. Dawn peak of
      photosynthesis was only found in well watered plants but was markedly reduced by
      the short term water stress of a fohn-storm. Morning fog with its higher diffuse
      light intensity compared with clear days increased photosynthetic CO2 uptake
      considerably. Even in well watered plants nocturnal CO2 uptake and malate
      accumulation were strongly affected by fohn indicating that the water vapour
      pressure deficit during the night determines the degree of acidification. 

PMID- 24458500
TI  - Clinical characteristics and outcomes of patients with pleural infections due to
      Stenotrophomonas maltophilia at a medical center in Taiwan, 2004-2012.
AB  - Stenotrophomonas maltophilia can cause various clinical diseases; however,
      pleural infections due to S. maltophilia are rare. We evaluated the clinical
      characteristics and outcomes of patients with pleural infections (complicated
      parapneumonic effusion or empyema) due to S. maltophilia who were treated at a
      medical center in Taiwan from 2004 to 2012. During the study period, 40 patients
      were treated for pleural infections due to S. maltophilia. The incidence of S.
      maltophilia pleural infections ranged from 2.66 per 1,000,000 patient-days in
      2009 to 12.44 per 1,000,000 patient-days in 2011. Most of the patients with S.
      maltophilia pleural infections were immunocompromised male adults and all of the
      infections were acquired in healthcare settings. The majority of patients had
      polymicrobial pleural infections (n = 31, 77.5 %) and the most common pathogen
      was Pseudomonas aeruginosa (n = 12). The causes of pleural infections due to S.
      maltophilia were pneumonia due to S. maltophilia in two patients (5 %), post
      surgical/tube thoracostomy in 26 (65 %) patients, and fistula (bronchopleural,
      esophagopleural and biliopleural) in 12 (30 %) patients. The 14-day and 30-day
      mortality rates were 32.5 % and 42.5 %, respectively. Pleural infections due to
      S. maltophilia are most commonly the result of surgical procedures, thoracostomy,
      and underlying fistulas. These infections are associated with a high mortality
      rate, especially among immunocompromised patients.

PMID- 24458502
TI  - The effects of alcohol on the consumption of hard drugs: regression discontinuity
      evidence from the National Longitudinal Study of Youth, 1997.
AB  - This paper estimates the effect of alcohol use on consumption of hard drugs using
      the exogenous decrease in the cost of accessing alcohol that occurs when
      individuals reach the minimum legal drinking age. By using a regression
      discontinuity design and the National Longitudinal Study of Youth 1997, I find
      that all measures of alcohol consumption, even alcohol initiation increase
      discontinuously at age 21 years. I also find evidence that consumption of hard
      drugs decreased by 1.5 to 2 percentage points and the probability of initiating
      the use of hard drugs decreased by 1 percentage point at the age of 21 years,
      while the intensity of use among users remained unchanged. These estimates are
      robust to a variety of specifications and also remain robust across different
      subsamples.

PMID- 24458501
TI  - Real-time monitoring of New Delhi metallo-beta-lactamase activity in living
      bacterial cells by 1H NMR spectroscopy.
AB  - Disconnections between in vitro responses and those observed in whole cells
      confound many attempts to design drugs in areas of serious medical need. A method
      based on 1D (1)H NMR spectroscopy is reported that affords the ability to monitor
      the hydrolytic decomposition of the carbapenem antibiotic meropenem inside
      Escherichia coli cells expressing New Delhi metallo-beta-lactamase subclass 1
      (NDM-1), an emerging antibiotic-resistance threat. Cell-based NMR studies
      demonstrated that two known NDM-1 inhibitors, L-captopril and
      ethylenediaminetetraacetic acid (EDTA), inhibit the hydrolysis of meropenem in
      vivo. NDM-1 activity in cells was also shown to be inhibited by spermine, a porin
      inhibitor, although in an in vitro assay, the influence of spermine on the
      activity of isolated NDM-1 protein is minimal. This new approach may have generic
      utility for monitoring reactions involving diffusible metabolites in other
      complex biological matrices and whole-cell settings, including mammalian cells.

PMID- 24458503
TI  - Percutaneous stenting of interrupted aortic arch to treat compressive myelopathy.
AB  - Neurological complications of coarctation of aorta include spontaneous SAH,
      intracerebral hemorrhage, and cerebral abscess. Interrupted aortic arch (IAA)
      present as compressive myelopathy is not known. We describe an adult male
      presenting to neurology department with progressive paraparesis and was detected
      to have IAA with intraspinal collaterals causing compressive myelopathy. He was
      successfully treated with percutaneous stenting of IAA with dramatic improvement
      in paraparesis. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24458504
TI  - Supramolecular ssDNA templated porphyrin and metalloporphyrin nanoassemblies with
      tunable helicity.
AB  - Free-base and nickel porphyrin-diaminopurine conjugates were formed by hydrogen
      bond directed assembly on single-stranded oligothymidine templates of different
      lengths into helical multiporphyrin nanoassemblies with highly modular structural
      and chiroptical properties. Large red-shifts of the Soret band in the UV/Vis
      spectroscopy confirmed strong electronic coupling among assembled porphyrin
      diaminopurine units. Slow annealing rates yielded preferentially right-handed
      nanostructures, whereas fast annealing yielded left-handed nanostructures. Time
      dependent DFT simulations of UV/Vis and CD spectra for model porphyrin clusters
      templated on the canonical B-DNA and its enantiomeric form, were employed to
      confirm the origin of observed chiroptical properties and to assign the helicity
      of porphyrin nanoassemblies. Molar CD and CD anisotropy g factors of dialyzed
      templated porphyrin nanoassemblies showed very high chiroptical anisotropy. The
      DNA-templated porphyrin nanoassemblies displayed high thermal and pH stability.
      The structure and handedness of all assemblies was preserved at temperatures up
      to +85  degrees C and pH between 3 and 12. High-resolution transition electron
      microscopy confirmed formation of DNA-templated nickel(II) porphyrin
      nanoassemblies and their self-assembly into helical fibrils with micrometer
      lengths.

PMID- 24458505
TI  - Effects of antidepressant drug exposure on gene expression in the developing
      cerebral cortex.
AB  - To clarify the basis of limited responses in children and adolescents to
      antidepressant treatments considered standard in the treatment of adult major
      depressive disorder, juvenile Sprague-Dawley rats were subjected to 21-day
      treatment with dissimilar antidepressant drugs fluoxetine, imipramine, or vehicle
      control. Total RNA was extracted from brain frontal cortices and hybridized to
      the Affymetrix 230.2 chip. A total of 18 microarrays were analyzed (i.e., six
      biological replicates in three treatment groups). Transcripts identified were
      validated using Taqman real-time quantitative PCR methodology, and the relative
      expression of each gene was also determined. In both the imipramine- and
      fluoxetine-treated animals, expression of six genes was down-regulated (ANOVA
      filtered gene expression data using dChip [version 2005]): Gpd1; Lrrn3; Sult1A1;
      Angptl4; Mt1a; Unknown. Furthermore, four genes were over-expressed: P4Ha1;
      RDG1311476; Rgc32; and SLC25A18-like by both imipramine and fluoxetine. These
      data demonstrate that antidepressant drugs interfere with the expression of genes
      involved in cell signaling, survival, and protein metabolism. Our results show
      that antidepressants regulate the induction of highly specific transcriptional
      programs in the developing frontal cortex. These findings provide novel insights
      into the long-term molecular actions of antidepressant drugs in the developing
      brain.

PMID- 24458506
TI  - Effect of foam rolling and static stretching on passive hip-flexion range of
      motion.
AB  - CONTEXT: Many athletes report that foam rollers help release tension in their
      muscles, thus resulting in greater range of motion (ROM) when used before
      stretching. To date, no investigators have examined foam rollers and static
      stretching. OBJECTIVE: To determine if foam rolling before static stretching
      produces a significant change in passive hip-flexion ROM. DESIGN: Controlled
      laboratory study. SETTING: Research laboratory. PARTICIPANTS: 40 subjects with
      less than 90 degrees  of passive hip-flexion ROM and no lower-extremity injury in
      the 6 mo before data collection. INTERVENTIONS: During each of 6 sessions,
      subjects' passive hip-flexion ROM was measured before and immediately after
      static stretching, foam rolling and static stretching, foam rolling, or nothing
      (control). To minimize accessory movement of the hip and contralateral leg,
      subjects lay supine with a strap placed across their hip and another strap
      located over the uninvolved leg just superior to the patella. A bubble
      inclinometer was then aligned on the thigh of the involved leg, with which
      subjects then performed hip flexion. MAIN OUTCOME MEASURE: Change in passive hip
      flexion ROM from the preintervention measure on day 1 to the postintervention
      measure on day 6. RESULTS: There was a significant change in passive hip-flexion
      ROM regardless of treatment (F3,17 = 8.06, P = .001). Subjects receiving foam
      roll and static stretch had a greater change in passive hip-flexion ROM compared
      with the static-stretch (P = .04), foam-rolling (P = .006), and control (P =
      .001) groups. CONCLUSIONS: Our results support the use of a foam roller in
      combination with a static-stretching protocol. If time allows and maximal gains
      in hip-flexion ROM are desired, foam rolling the hamstrings muscle group before
      static stretching would be appropriate in noninjured subjects who have less than
      90 degrees  of hamstring ROM.

PMID- 24458507
TI  - Virtual screening of the SAMPL4 blinded HIV integrase inhibitors dataset.
AB  - Several combinations of docking software and scoring functions were evaluated for
      their ability to predict the binding of a dataset of potential HIV integrase
      inhibitors. We found that different docking software were appropriate for each
      one of the three binding sites considered (LEDGF, Y3 and fragment sites), and the
      most suitable two docking protocols, involving Glide SP and Gold ChemScore, were
      selected using a training set of compounds identified from the structural data
      available. These protocols could successfully predict respectively 20.0 and 23.6
      % of the HIV integrase binders, all of them being present in the LEDGF site. When
      a different analysis of the results was carried out by removing all alternate
      isomers of binders from the set, our predictions were dramatically improved, with
      an overall ROC AUC of 0.73 and enrichment factor at 10 % of 2.89 for the
      prediction obtained using Gold ChemScore. This study highlighted the ability of
      the selected docking protocols to correctly position in most cases the ortho
      alkoxy-carboxylate core functional group of the ligands in the corresponding
      binding site, but also their difficulties to correctly rank the docking poses.

PMID- 24458508
TI  - Periodized resistance training with and without supplementation improve body
      composition and performance in older men.
AB  - PURPOSE: To examine the effects of 12 weeks of periodized resistance training
      (RT) with and without combined creatine and whey protein supplementation on
      changes in body composition, muscular strength, and functional performance.
      METHODS: Twenty-two male volunteers (68.1 +/- 6.1 years) were randomly assigned
      to one of three groups: RT plus supplementation (RTS, n = 7); RT only (RT, n =
      7); or control (C, n = 8). RTS consumed 0.3 g/kg/day of creatine for 5 days
      followed by 0.07 g/kg/day. RTS also consumed one 35 g liquid protein ready-to
      drink daily. RT and RTS trained 3 days/week. RESULTS: Following 12 weeks of
      training, there were no significant differences in the main measured outcome
      variables between RT and RTS. RTS increased relative (% change) lean body mass
      (LBM, 3.3 +/- 3.1 %) compared with C (p = 0.01). Compared to baseline, RT
      increased LBM at week 6 (60.2 +/- 8.3 to 61.6 +/- 9.4 kg; p < 0.05), and
      decreased fat mass (20.8 +/- 4.2 to 19.0 +/- 3.9 kg; p = 0.05) and percentage
      body fat at week 12 (25.7 +/- 3.8 to 23.8 +/- 4.0 %; p = 0.05); RTS increased LBM
      at week 6 (p < 0.01) and week 12 (56.4 +/- 4.3 to 58.2 +/- 3.4 kg; p < 0.01), and
      decreased percentage body fat at week 12 (23.9 +/- 4.4 to 22.0 +/- 4.4 %; p <
      0.01). In addition, compared to C, relative bench press 1-RM increased for RTS
      (72.4 +/- 62.2 %; p < 0.01) and RT (50.1 +/- 21.5 %; p = 0.05); relative leg
      press 1-RM increased for RTS (129.6 +/- 39.4 %; p < 0.0001) and RT (112.9 +/-
      22.7 %; p < 0.0001); RTS increased relative Margaria stair-climbing power (38.3
      +/- 30.4 %; p < 0.05); and, relative 400-m walk time decreased for RT (-11 +/-
      9.2 %; p < 0.05) and RTS (-9.6 +/- 9.4 %; p = 0.05). RT increased estimated
      VO2Max at week 6 (p < 0.01) and 12 (34.6 +/- 1.9 to 36.4 +/- 2.7 ml/kg/min; p =
      0.01) compared to baseline. Lastly, RTS increased estimated VO2Max at week 12
      (36.3 +/- 2.7 to 37.5 +/- 3.3 ml/kg/min; p = 0.05) compared to baseline.
      CONCLUSION: Creatine and whey protein supplementation may not provide additional
      benefits in older adults performing periodized RT to augment muscular and
      functional performance.

PMID- 24458509
TI  - Quinolone resistance genes (qnrA and qnrS) in bacteriophage particles from
      wastewater samples and the effect of inducing agents on packaged antibiotic
      resistance genes.
AB  - OBJECTIVES: This study quantifies quinolone antibiotic resistance genes (qnrA and
      qnrS) in DNA of phage particles isolated from faecally polluted waters and
      evaluates the influence of phage inducers on the abundance of antibiotic
      resistance genes in packaged DNA. METHODS: qnrA and qnrS were quantified by qPCR
      in DNA of phage particles isolated from 18 raw urban wastewater samples, 18 river
      samples and 28 archived samples of animal wastewater. The bacterial fraction of
      the samples was treated with mitomycin C, ciprofloxacin, EDTA or sodium citrate
      under different conditions, and the number of resistance genes in DNA of phage
      particles was compared with the non-induced samples. RESULTS: qnrA was more
      prevalent than qnrS, with 100% of positive samples in urban wastewater and river
      and 71.4% of positive samples in animal wastewater. Densities of qnrA ranged from
      2.3 * 10(2) gene copies (GC)/mL in urban wastewater to 7.4 * 10(1) GC/mL in
      animal wastewater. qnrS was detected in 38.9% of urban wastewater samples, in
      22.2% of river samples and only in one animal wastewater sample (3.6%). Despite
      the lower prevalence, qnrS densities reached values of 10(3) GC/mL. Both qnr
      genes and other resistance genes assayed (blaTEM and blaCTX-M) showed a
      significant increase in DNA of phage particles when treated with EDTA or sodium
      citrate, while mitomycin C and ciprofloxacin showed no effect under the different
      conditions assayed. CONCLUSIONS: This study confirms the contribution of phages
      to the mobilization of resistance genes and the role of the environment and
      certain inducers in the spread of antibiotic resistance genes by means of phages.

PMID- 24458510
TI  - Antiviral activity of baicalin against influenza virus H1N1-pdm09 is due to
      modulation of NS1-mediated cellular innate immune responses.
AB  - OBJECTIVES: Baicalin, a flavonoid, has been shown to have antiviral and anti
      inflammatory activities, although the mechanism of action has been unknown.
      Therefore, attempts were made to analyse the mechanism behind the antiviral
      effects of baicalin using an influenza A virus (IAV) model in vitro and in vivo.
      METHODS: Baicalin's anti-influenza activity was elucidated (in vitro and in vivo)
      utilizing pandemic influenza strain A/H1N1/Eastern India/66/pdm09 (H1N1-pdm09).
      Anti-influenza activity was measured by plaque inhibition, fluorescent focus
      forming units (ffu) and quantifying viral transcripts using quantitative real
      time PCR following treatment with baicalin in a dose- and time-dependent manner.
      The role of the IAV non-structural protein 1 (NS1) gene in modulating host
      responses was measured by immunoblotting, co-immunoprecipitation and molecular
      docking. RESULTS: Baicalin treatment following IAV infection revealed up
      regulation of interferon (IFN)-induced antiviral signalling and decreased
      phosphoinositide 3-kinase/Akt (PI3K/Akt) activation compared with infected,
      untreated controls. Baicalin exerts its antiviral effects by modulating the
      function of the IAV-encoded NS1 protein. NS1 has been shown to counteract
      cellular antiviral responses by down-regulating IFN induction and up-regulating
      PI3K/Akt signalling. Baicalin disrupted NS1-p85beta binding. Molecular docking
      predicted the binding site of baicalin in the RNA binding domain (RBD) of NS1.
      Site-directed mutagenesis within the RBD region of NS1 and the difference in the
      fluorescence quenching pattern of full-length NS1 and mutant NS1 proteins in the
      presence of baicalin confirmed the interaction of baicalin with the NS1 RBD.
      Amino acid residues 39-43 of the NS1 RBD were found to be crucial for the
      baicalin-NS1 interaction. CONCLUSIONS: Overall, this study highlights that
      baicalin exerts its anti-influenza virus activity by modulating viral protein
      NS1, resulting in up-regulation of IFN-induced antiviral signalling and a
      decrease in PI3K/Akt signalling in cells.

PMID- 24458511
TI  - Viral rebound after switch to maraviroc/raltegravir dual therapy in highly
      experienced and virologically suppressed patients with HIV-1 infection.

PMID- 24458512
TI  - Phylogenetic polymorphisms in antibiotic resistance genes of the Mycobacterium
      tuberculosis complex.
AB  - OBJECTIVES: Sequence analysis of known antibiotic resistance genes of the
      Mycobacterium tuberculosis complex (MTBC) is increasingly being used to infer
      phenotypic resistance to a variety of antibiotics. However, a clear understanding
      of the genotype-phenotype relationship is required to interpret genotypic
      susceptibility results accurately. In this context, it is particularly important
      to distinguish phylogenetically informative neutral polymorphisms from true
      resistance-conferring mutations. METHODS: Using a collection of 71 strains that
      encompasses all major MTBC genotypes, we mapped the genetic diversity in 18 genes
      that are known to be involved or were previously implicated in antibiotic
      resistance to eight current as well as two novel antibiotics. This included
      bedaquiline, capreomycin, ethambutol, fluoroquinolones, isoniazid, PA-824, para
      aminosalicylic acid, prothionamide, rifampicin and streptomycin. Moreover, we
      included data from one of our prior studies that focused on two of the three
      known pyrazinamide resistance genes. RESULTS: We found 58 phylogenetic
      polymorphisms that were markers for the genotypes M. tuberculosis Beijing,
      Haarlem, Latin American-Mediterranean (LAM), East African Indian (EAI),
      Delhi/Central Asian (CAS), Ghana, Turkey (Tur), Uganda I and II, Ural and X-type,
      as well as for Mycobacterium africanum genotypes West African I (WA I) and II (WA
      II), Mycobacterium bovis, Mycobacterium caprae, Mycobacterium pinnipedii,
      Mycobacterium microti and Mycobacterium canettii. CONCLUSIONS: This study
      represents one of the most extensive overviews of phylogenetically informative
      polymorphisms in known resistance genes to date, and will serve as a resource for
      the design and interpretation of genotypic susceptibility assays.

PMID- 24458513
TI  - Infection control and prevention measures to reduce the spread of vancomycin
      resistant enterococci in hospitalized patients: a systematic review and meta
      analysis.
AB  - OBJECTIVES: Vancomycin-resistant enterococci (VRE) represent a major problem in
      healthcare settings worldwide. It is still unclear which is the most effective
      infection control and prevention (ICP) measure to reduce the spread of hospital
      acquired VRE. METHODS: Cochrane databases, MEDLINE, EMBASE and CINAHL were
      searched until June 2012 to find studies comparing wards/hospitals where ICP
      measures to prevent VRE transmission were investigated. In the absence of
      heterogeneity, a fixed-effects model was used to estimate the pooled risk ratio
      (RR). Study quality was assessed according to Cochrane Effective Practice and
      Organisation of Care (EPOC) criteria. RESULTS: The search strategy retrieved 549
      studies and 9 studies (1 randomized clinical trial, 3 controlled clinical trials
      and 5 interrupted time series) with 30, 949 participants were included. The
      overall study quality was low. Implementation of hand hygiene was associated with
      a 47% decrease in the VRE acquisition rate (pooled RR 0.53, 95% CI 0.39-0.73,
      I(2) 26%) while contact precautions did not significantly reduce the VRE
      acquisition rate (pooled RR 1.08, 95% CI 0.63-1.83, I(2) 0%). Due to the low
      number of studies, meta-analysis was not applied for surveillance screening,
      environmental cleaning and antibiotic formulary interventions. No studies were
      available on the effectiveness of isolation and cohorting of patients and staff.
      CONCLUSIONS: Available evidence on the ICP measures to reduce VRE spread in adult
      hospitalized patients is poor. This systematic review suggests a significant role
      for the implementation of hand hygiene. Further studies with appropriate study
      design are urgently needed to define ICP measures able to reduce the acquisition
      of VRE among hospitalized patients.

PMID- 24458514
TI  - Gender-specific associations between physical functioning, bone quality, and
      fracture risk in older people.
AB  - The aim of this study was to investigate which parameters of physical functioning
      are associated with bone quality and fracture risk and whether gender-specific
      differences exist within these associations. We studied 1,486 participants of the
      Longitudinal Aging Study Amsterdam. As measures of physical functioning, handgrip
      strength, physical performance, and level of physical activity were assessed. To
      assess bone quality, broadband ultrasound attenuation (BUA) and speed of sound
      (SOS) were measured at baseline using quantitative ultrasound and bone mineral
      density (BMD) at baseline and after 3 years by dual-energy X-ray absorptiometry.
      In addition, fracture incidence over 6 years was assessed. After adjustment for
      confounders (age, serum 25[OH]D, smoking, and body weight), in men, physical
      performance was positively related to BUA, SOS, and BMD cross-sectionally and to
      BMD longitudinally. Using Cox proportional hazards model, in men higher handgrip
      strength and physical performance were associated with reduced fracture risk
      after adjustment for confounders (hazard ratio [HR] 0.96, 95 % confidence
      interval [CI] 0.92-0.99, and HR 0.89, 95 % CI 0.80-0.98, respectively). In women,
      a moderate level of physical activity was related to reduced fracture risk (HR
      0.57, 95 % CI 0.33-0.99). In conclusion, in men, higher handgrip strength and
      physical performance are related to higher bone quality and reduced fracture
      risk, whereas in women, a moderate to high level of physical activity is
      associated with reduced fracture risk. These measurements may contribute to the
      identification of individuals at high fracture risk. Both the causality of and
      explanations for gender-specific differences in these relationships remain
      subject to further studies.

PMID- 24458515
TI  - EURECCA consensus conference highlights about colorectal cancer clinical
      management: the pathologists expert review.
AB  - Care for patients with colon and rectal cancer has improved in the last 20 years;
      however, a considerable variation still exists in cancer management and outcome
      between European countries. Large variation is also apparent between national
      guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is
      the acronym of European Registration of Cancer Care, is aiming at defining core
      treatment strategies and developing a European audit structure in order to
      improve the quality of care for all patients with colon and rectal cancer. In
      December 2012, the first multidisciplinary consensus conference about cancer of
      the colon and rectum was held. The expert panel consisted of representatives of
      European scientific organizations involved in cancer care of patients with colon
      and rectal cancer and representatives of national colorectal registries. 

PMID- 24458516
TI  - High GOLPH3 expression is associated with a more aggressive behavior of
      epithelial ovarian carcinoma.
AB  - Overexpression of GOLPH3 (Golgi phosphoprotein 3, 34 kDa) is associated with the
      progression of many solid tumor types leading to an unfavorable clinical outcome.
      The present study examined the association between GOLPH3 expression and tumor
      development, clinicopathological factors, and prognosis of epithelial ovarian
      carcinoma. GOLPH3 expression was examined by immunohistochemistry in 18 normal
      ovarian samples, 28 benign tumors, 55 serous borderline ovarian tumors, and 135
      epithelial ovarian carcinomas. The association of GOLPH3 expression with clinical
      characteristics, response to chemotherapy, and overall survival of epithelial
      ovarian carcinoma patients was analyzed on fresh tissue samples. GOLPH3 mRNA and
      protein expression in ovarian cancer and normal ovarian tissues were detected by
      real-time quantitative RT-PCR and Western blotting, respectively. The results are
      the following: (1) GOLPH3 immunostaining localized to the cytoplasm in two
      patterns, condensed into large granules with perinuclear distribution, and
      dispersed in the cytoplasm as fine granules. (2) GOLPH3 expression was higher in
      epithelial ovarian carcinoma than in normal ovarian tissues at the mRNA and
      protein level. The frequency of high-level expression of GOLPH3 increased
      progressively from benign (cystadenoma) to borderline neoplasms to malignant
      lesions. (3) Dispersed cytoplasmic GOLPH3 expression in epithelial ovarian
      carcinoma patients was highly correlated with FIGO stage (p < 0.001), tumor
      histological grade (p = 0.003), lymph node involvement (p = 0.001), and
      chemotherapy response (p = 0.034). (4) A dispersed pattern of GOLPH3 expression
      was an independent prognostic factor for poor overall survival. Patients with low
      dispersed cytoplasmic GOLPH3 expression had significantly longer overall survival
      than patients with high dispersed cytoplasmic expression. In contrast, GOLPH3
      condensed expression was not correlated with clinicopathological features,
      chemotherapy response, or prognosis. GOLPH3 gene expression might play a role in
      tumorigenesis in epithelial ovarian carcinoma as upregulation of GOLPH3
      expression is associated with a more aggressive tumor phenotype. GOLPH3
      immunohistochemistry may be of value to predict the outcome of ovarian carcinoma
      patients.

PMID- 24458517
TI  - Cystic and micropapillary epithelial changes of peribiliary glands might
      represent a precursor lesion of biliary epithelial neoplasms.
AB  - A tumorigenic role of peribiliary glands (PBGs) has been suggested recently. This
      study was performed to clarify the histological characteristics of PBGs showing
      cystic and micropapillary epithelial changes. From histological sections of a
      total of 938 autopsy livers, cases with cystic and micropapillary changes of the
      epithelial cells of intrahepatic PBGs were collected. PBGs with cystic change
      that lacked micropapillary epithelial changes were referred to as cystic lesion.
      Mucin staining and immunohistochemical analysis were performed, and the results
      were compared between cystic and micropapillary (C-P) lesions and cystic lesions.
      C-P and cystic lesions were observed in 9 (1 %) and 40 (4 %) , respectively. The
      atypia of micropapillary epithelium was usually mild, but in a single case,
      invasive adenocarcinoma accompanied a C-P lesion. Abundant mucin expression was
      observed in all cases of C-P lesion, which was similar to mucinous acini of
      normal PBGs rather than serous acini. Immunohistochemical analysis showed that
      MUC5AC was more frequently expressed in C-P lesions than in cystic lesions.
      Immunohistochemical expression of cyclin D1 and S100P was characteristically
      found in C-P lesions. Mean Ki-67 labeling index of C-P lesions was significantly
      higher than that of cystic lesions. The immunoprofile of C-P lesions was similar
      to that of the branch-type intraductal papillary mucinous neoplasm of the
      pancreas. These results suggest that C-P lesions may have neoplastic features and
      might represent a precursor of biliary epithelial neoplasms, including branch
      type intraductal papillary neoplasm of the bile duct as well as mucin-producing
      cholangiocarcinoma, a concept that we have recently proposed. 

PMID- 24458518
TI  - Metastatic melanoma mimicking solitary fibrous tumor: report of two cases.
AB  - Malignant melanomas are known for their remarkable morphological variation and
      aberrant immunophenotype with loss of lineage-specific markers, especially in
      recurrences and metastases. Hot spot mutations in BRAF, NRAS, GNAQ, and GNA11 and
      mutations in KIT are oncogenic events in melanomas. Therefore, genotyping can be
      a useful ancillary diagnostic tool. We present one case each of recurrent and
      metastatic melanoma, both showing histological and immunohistochemical features
      of solitary fibrous tumor (SFT). Mutational analysis detected BRAF and NRAS
      mutations in the primary and secondary lesions, respectively. This result
      confirmed the diagnosis of recurrent/metastastic melanoma. 

PMID- 24458519
TI  - [Unclear splenic lesion with rectal cancer].

PMID- 24458520
TI  - [Rare coincidence in the region of the cardia. Potential pitfall in surgical
      treatment].

PMID- 24458521
TI  - Fibronectin is a serum biomarker for Duchenne muscular dystrophy.
AB  - PURPOSE: To identify and validate serum biomarkers for the progression of
      Duchenne muscular dystrophy (DMD) using a MS-based bottom-up pipeline.
      EXPERIMENTAL DESIGN: We used a bottom-up proteomics approach, including a protein
      concentration equalization step, different proteolytic digestions, and MS
      detection schemes, to identify candidate biomarkers in serum samples from control
      subjects and DMD patients. Fibronectin was chosen for follow-up based on the
      differences in peptide spectral counts and sequence coverage observed between the
      DMD and control groups. Subsequently, fibronectin levels were determined with
      ELISA in 68 DMD patients, 38 milder Becker muscular dystrophy patients, 33
      patients with other neuromuscular disorders, and 15 age-matched adult and child
      controls. RESULTS: There was a significant increase in fibronectin levels in DMD
      patients compared to age-matched controls. Fibronectin levels in patients with
      Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable
      to control levels. Progressive elevation in fibronectin levels was observed in
      longitudinal samples from 22 DMD patients followed up for a period of 6 months up
      to 4 years. CONCLUSION AND CLINICAL RELEVANCE: This study suggests that serum
      fibronectin levels may constitute a promising biomarker to monitor disease
      progression in DMD patients.

PMID- 24458523
TI  - Chlorophyll-protein-complexes of thylakoids of wild type and chlorophyll b
      mutants of Arabidopsis thaliana.
AB  - Pigment-protein-complexes of two chlorophyll b deficient mutants of Arabidopsis
      and from the wild type were separated electrophoretically. Light-harvesting
      proteins were absent in the chlorophyll b free mutant ch(1) and their amount was
      reduced in the mutant ch(2) which has a reduced content of chlorophyll b. The
      ratio of CPa:CP I increased with decreasing chlorophyll b content which indicated
      that the stoichiometry of photosystem II to photosystem I is not constant. 

PMID- 24458522
TI  - Behavioral profile in RASopathies.
AB  - Here, we describe neurobehavioral features in patients with RASopathies (i.e.,
      Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous
      syndrome), developmental disorders caused by mutations in genes coding
      transducers participating in the RAS-MAPK signaling cascade. Parents of 70
      individuals with a RASopathy were asked to fill out the following questionnaires:
      Child Behavior Checklist (CBCL), Social Communication Questionnaire version
      lifetime (SCQ-L), and Modified Checklist for Autism in toddlers (M-CHAT). Data
      analysis indicated high rates of internalizing (37%) and externalizing problems
      (31%) on CBCL. Scores over the cut-off were documented in 64% of patients with
      cardiofaciocutaneous syndrome, 44% with Costello syndrome, and 12% with Noonan
      syndrome on SCQ-L/M-CHAT. Our findings indicate that mutations promoting
      dysregulation of the RAS-MAPK cascade mark an increased psychopathological risk
      and highlight that autistic-like behavior could be underdiagnosed in patients
      with RASopathies.

PMID- 24458524
TI  - Net photosynthetic rate of sour cherry (Prunus cerasus L. 'Montmorency') during
      the growing season with particular reference to fruiting.
AB  - Diurnal and seasonal net photosynthetic rates (Pn) of sour cherry were
      determined. Leaf Pn was not significantly affected by shoot excision. Under
      constant environmental conditions (PFD, 1200 MUmol m(-2)s(-1); temp. 25; relative
      humidity, 80-90%) there was no significant diurnal fluctuation in Pn for
      individual leaves. However, there was a pronounced fluctuation in Pn for whole
      trees measured under constant temperature but natural variation in sunlight from
      sunrise to sunset. Maximum Pn occurred before solar noon, remained constant for 1
      2 hr, then declined. Photosynthetic rate of recently expanded leaves fluctuated
      through out the season but, in general, was greatest in the spring as leaves
      expanded, reached a peak, remained stable for several weeks, then gradually
      declined. The Pn of leaves on terminal shoots was not significantly different
      from the Pn of leaves on spurs of the same physiological age. The presence of
      fruit did not have a consistent effect on the Pn of sour cherry leaves. 

PMID- 24458525
TI  - Isolation of chlorophyll-protein complexes and quantification of electron
      transport components in Synura petersenii and Tribonema aequale.
AB  - The chlorophyll-protein complexes of the yellow alga Synura petersenii
      (Chrysophyceae) and the yellow-green alga Tribonema aequale (Xanthophyceae) were
      studied. The sodiumdodecylsulfate/sodiumdesoxycholate solubilized photosynthetic
      membranes of these species yielded three distinct pigment-protein complexes and a
      non-proteinuous zone of free pigments, when subjected to SDS polyacrylamid gel
      electrophoresis. The slowest migrating protein was identical to complex I (CP I),
      the P-700 chlorophyll a-protein, which possessed 60 chlorophyll a molecules per
      reaction center in Tribonema and 108 in Synura. The zone of intermediate mobility
      contained chlorophyll a and carotenoids. The absorption spectrum of this complex
      was very similar to the chlorophyll a-protein of photosystem II (CP a), which is
      known from green plants. The fastest migrating pigment protein zone was
      identified as a light-harvesting chlorophyll-protein complex. In Synura this
      protein was characterized by the content of chlorophyll c and of fucoxanthin.
      Therefore this complex will be named as LH Chl a/c-fucocanthin protein. In
      addition to the separation of the chlorophyll-protein complexes the cellular
      contents of P-700, cytochrome f (bound cytochrome) and cytochrome c-553 (soluble
      cytochrome) were measured. The stoichiometry of cytochrome f: cytochrome c-553:P
      700 was found to be 1:4:2.4 in Tribonema and 1:6:3.4 in Synura. 

PMID- 24458526
TI  - Elevated atmospheric partial pressure of carbon dioxide and dry matter production
      of konjak (Amorphophallus konjac K. Koch).
AB  - Konjak (Amorphophallus konjac K. Koch) was grown under normal (350 MUbar) or
      enriched (700 MUbar) CO2 partial pressure in glasshouses kept at 33/26 degrees C.
      Doubling the CO2 partial pressure resulted in twice the yield of corm because the
      net CO2 assimilation rate doubled and, due to the simple source-sink
      relationship, the increased production was partitioned to the corm. The response
      to CO2 of assimilation by konjak is discussed in relation to its original habitat
      in the tropics. 

PMID- 24458527
TI  - Changes of the chlorophyll fluorescence induction kinetics of C3 and CAM plants
      during day/night cycles.
AB  - The induction kinetics of the 680 nm chlorophyll fluorescence were measured on
      attached leaves of Kalanchoe daigremontiana R. Hamet et Perr. (CAM plant), Sedum
      telephium L. and Sedum spectabile Bor. (C3 plant in spring, CAM plant in summer)
      and Raphanus sativus L. (C3 plant) at three different times during a 12/12h
      day/night cycle. During the fluorescence transient the fluorescence intensity at
      the O, P and T-level (fO, fmax, fst,) was different for the plant species tested;
      this may be due to their different leaf structure, pigment composition and
      organization of their photosystems. The kinetics of the fluorescence induction
      depended on the time of preillumination or dark adaptation during the light/dark
      cycle but not on the type of primary CO2 fixation mechanism (C3 and CAM). For
      dark adapted leaves measured either at the end of the dark phase or after dark
      adaptation of plants taken from the light phase a higher P-level fluorescence, a
      higher variable fluorescence (P-O) and a larger complementary area were found
      than for leaves of plants taken directly from the light phase. This indicates the
      presence of largely oxidized photosystem 2 acceptor pools during darkness. During
      the light phase the fluorescence decline after the P-level was faster than during
      the dark phase; from this we conclude that the light adaptation of the
      photosynthetic apparatus (state 1-> state 2 transition, Delta pH) during the
      induction period proceeded faster in plants taken from the light phase than in
      plants taken from the dark phase. 

PMID- 24458528
TI  - Photochemical activities and organization of photosynthetic apparatus of C3 and C
      4 plants grown under different light intensities.
AB  - Changes in the photochemical activities, influenced by variation in the growth
      light intensity, were followed in typical C3 (Phaseolus, Ipomoea) and C4
      (Amaranthus, Sorghum) plants. Progressive decrease in the growth light intensity
      accelerated the O-P fluorescence induction in whole leaves. Such acceleration of
      the fluorescence kinetics was found to be not due to enhanced photosystem II
      activity but possibly a result of reduced rate of electron flow between the two
      photosystems. This is supported by 4 lines of evidence: (1) by the Hill activity
      determined in the presence of electron acceptors functioning before and after
      plastoquinone; (2) the photosynthetic unit size determined after flash excitation
      showing variations that were apparently too small to account for the changes
      observed fluorescence induction; (3) modification of the kinetics of second-range
      light-induced absorbance changes at 520 nm; and (4) absence of significant
      changes in the ratio of P700/total chlorophyll ratio.The P700/cytochrome f ratio,
      however, increased from the usual 1-1.5 to 3-4 in plants grown under 9% sunlight.
      Increase in the P700/cytochrome f ratio was found to be due to a decrease in the
      cytochrome f/chlorophyll ratio, and this was due to perhaps to a simultaneous
      increase in chlorophyll and decrease in cytochrome content. 

PMID- 24458529
TI  - Chlorophyll fluorescence yield changes as a tool in plant physiology I. The
      measuring system.

PMID- 24458530
TI  - A new evaluation of chlorophyll absorption in photosynthetic membranes.
AB  - The three major chlorophyll-proteins of spinach chloroplasts were solubilized
      with digitonin and isolated by electrophoresis with deoxycholate. The gel bands
      were identified from their absorption and fluorescence spectra measured at 77 K.
      The slowest moving band was a Photosystem I complex (CPI); the second, a
      Photosystem II complex (Cpa); and the third, a chlorophyll a-b, antenna complex
      (LHCP). When absorption spectra (630-730 nm) of the bands were added in the
      proportions found in the gel, the sum closely matched the absorption of the
      chloroplasts both before and after solubilization. Thus these spectra represent
      the native absorption of the major antenna chlorophyll-proteins of green plants.
      Each of these spectra was resolved with a computer assisted, curve-fitting
      program into 8 mixed Gaussian-Lorentzian shaped components. The major, Chl a
      components in the 3 fractions were different both in peak positions and
      bandwidths. This result suggests that each chlorophyll-protein has its own unique
      set of chlorophyll a spectral forms or components. 

PMID- 24458531
TI  - Imbalance of Ca2+ and K+ fluxes in C6 glioma cells after PDT measured with
      scanning ion-selective electrode technique.
AB  - Photodynamic therapy (PDT) possesses the capacity to lead to death of C6 glioma
      in vitro and in vivo. The purpose of this study was to investigate whether Ca(2+)
      and K(+) homeostasis of C6 glioma cells were affected by PDT. C6 glioma cells
      were randomly divided into five groups: control group, Hematoporphyrin derivative
      (HpD) group (10 mg/l, without irradiation), PDT group (HpD 10 mg/l +
      irradiation), PDT&6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) group (HpD 10 mg/l
      + CNQX 50 mol/l + irradiation), and HpD&CNQX group (HpD 10 mg/l + CNQX 50 mol/l,
      without irradiation). Glioma cells in PDT and PDT&CNQX group were subjected to
      PDT. Cells in PDT&CNQX group were administered alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) glutamate receptor antagonist CNQX prior to PDT on
      C6 glioma cells. The changes of Ca(2+) and K(+) fluxes were studied by using a
      non-invasive scanning ion-selective electrode technique (SIET). Morphology of C6
      cells was observed with optical microscopy. PDT induced Ca(2+) influx and K(+)
      efflux significantly, which resulted in death of C6 cells. When AMPA glutamate
      receptor antagonist CNQX was applied, Ca(2+) influx and K(+) efflux were partly
      blocked up and viability of C6 cells increased. These results indicate that
      Ca(2+) influx and K(+) efflux may correlate with the treatment effects of PDT on
      C6 glioma cells.

PMID- 24458532
TI  - Ablation of porcine bone tissue with an ultrashort pulsed laser (USPL) system.
AB  - Ultrashort pulsed lasers (USPLs) represent a new generation of laser systems in
      the field of biophotonical applications. In terms of a pilot project, the study
      was carried out to evaluate the ablation parameters of bone tissue regarding the
      medical use of such a laser technology in dentistry. Specimens from ribs of
      freshly slaughtered pigs were assembled and irradiated with an USP Nd:YVO4 laser
      (pulse duration 8 ps at 1,064 nm with repetition rates between 50 and 500 kHz)
      using eligible average output powers in the range of 3.5-9 W and fluences between
      1 and 2.5 J/cm(2). Square-shaped cavities of 1-mm edge length in the bone
      compacta were created employing a scanner system. Cavities were analyzed with an
      optical profilometer to determine the ablated volume. Ablation rate was
      calculated by the ablated volume and the recorded irradiation time by the scanner
      software. Additionally, samples were examined histologically to investigate side
      effects of the surrounding tissue. Formed cavities showed a precise and sharp
      edged appearance in bone compacta. Optimized ablation rate of 5.2 mm(3)/min
      without any accompanying side effects was obtained with an average output power
      of 9 W, a pulse repetition rate of 500 kHz, and an applied fluence of 2.5
      J/cm(2). Provided that the used laser system will be advanced and adjusted for
      clinical applications, the outcome of this study shows auspicious possibilities
      for the use of USPL systems in the preparation of bone tissue.

PMID- 24458533
TI  - Di-(2-ethylhexyl) phthalate and bisphenol A exposure impairs mouse primordial
      follicle assembly in vitro.
AB  - Bisphenol-A (BPA) and diethylhexyl phthalate (DEHP) are estrogenic compounds
      widely used in commercial plastic products. Previous studies have shown that
      exposure to such compounds have adverse effects on various aspects of mammalian
      reproduction including folliculogenesis. The objective of this study was to
      examine the effects of BPA and DEHP exposure on primordial follicle formation. We
      found that germ cell nest breakdown and primordial follicle assembly were
      significantly reduced when newborn mouse ovaries were exposed to 10 or 100 MUM
      BPA and DEHP in vitro. Moreover, BPA and DEHP exposure increased the number of
      TUNEL positive oocytes and the mRNA level of the pro-apoptotic gene Bax in
      oocytes. These effects were associated with decreased expression of oocyte
      specific genes such as LIM homeobox 8 (Lhx8), factor in the germline alpha
      (Figla), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and newborn
      ovary homeobox (Nobox). Interestingly, BPA and DEHP exposure also prevented DNA
      demethylation of CpG sites of the Lhx8 gene in oocytes, a process normally
      associated with folliculogenesis. Finally, folliculogenesis was severely impaired
      in BPA and DEHP exposed ovaries after transplantation into the kidney capsules of
      immunodeficient mice. In conclusion, BPA and DEHP exposures impair mouse
      primordial follicle assembly in vitro.

PMID- 24458534
TI  - Indigenous American species of the Bemisia tabaci complex are still widespread in
      the Americas.
AB  - Bemisia tabaci is a complex of at least 36 putative cryptic species. Since the
      late 1980s, the Middle East-Asia Minor 1 species (MEAM1, formerly known as the B
      biotype), has emerged in many tropical and subtropical regions of the world and
      in some areas has displaced the indigenous populations of B. tabaci. Based on
      analysis of the mtCOI gene, two indigenous species native to America have been
      reported: New World (NW, formerly the A biotype) and New World 2 (NW2). NW is
      present at least in Argentina, Brazil, Martinique, Mexico, Texas and Venezuela,
      and NW2 in Argentina, Bolivia and Brazil. Wild plants (Euphorbia sp. and Ipomoea
      sp.), as well as important crops such as tomato, bean and cotton, are still hosts
      for native B. tabaci populations in the Americas. MEAM1 has not completely
      displaced the native B. tabaci from the Americas.

PMID- 24458535
TI  - Bioactive nanocomposite PLDL/nano-hydroxyapatite electrospun membranes for bone
      tissue engineering.
AB  - New nanocomposite membranes with high bioactivity were fabricated using the
      electrospinning. These nanocomposites combine a degradable polymer poly(L/DL)
      lactide and bone cell signaling carbonate nano-hydroxyapatite (n-HAp). Chemical
      and physical characterization of the membranes using scanning electron
      microscopy, Fourier transform infrared spectroscopy and the wide angle X-ray
      diffraction evidenced that nanoparticles were successfully incorporated into the
      fibers and membrane structure. The incorporation of the n-HAp into the structure
      increased significantly the mineralization of the membrane in vitro. It has been
      demonstrated that after a 3-day incubation of composite membrane in the Simulated
      Body Fluid a continuous compact apatite layer was formed. In vitro experiments
      demonstrated that the incorporation of n-HAp significantly improved cell
      attachment, upregulated cells proliferation and stimulated cell differentiation
      quantified using Alkaline Phosphatase and OsteoImage tests. In conclusion, the
      results demonstrated that the addition of n-HAp provided chemical cues that were
      a key factor that regulated osteoblastic differentiation.

PMID- 24458536
TI  - Design of ratiometric fluorescent probes based on arene-metal-ion interactions
      and their application to Cd(II) and hydrogen sulfide imaging in living cells.
AB  - Non-coordinative interactions between a metal ion and the aromatic ring of a
      fluorophore can act as a versatile sensing mechanism for the detection of metal
      ions with a large emission change of fluorophores. We report the design of
      fluorescent probes based on arene-metal-ion interactions and their biological
      applications. This study found that various probes having different fluorophores
      and metal binding units displayed significant emission redshift upon complexation
      with metal ions, such as Ag(I), Cd(II), Hg(II), and Pb(II). X-ray crystallography
      of the complexes confirmed that the metal ions were held in close proximity to
      the fluorophore to form an arene-metal-ion interaction. Electronic structure
      calculations based on TDDFT offered a theoretical basis for the sensing
      mechanism, thus showing that metal ions electrostatically modulate the energy
      levels of the molecular orbitals of the fluorophore. A fluorescent probe was
      successfully applied to the ratiometric detection of the uptake of Cd(II) ions
      and hydrogen sulfide (H2S) in living cells. These results highlight the utility
      of interactions between arene groups and metal ions in biological analyses.

PMID- 24458537
TI  - The effect of disease duration and disease activity on the risk of cardiovascular
      disease in rheumatoid arthritis patients.
AB  - OBJECTIVE: Disease duration and disease activity may be associated with an
      increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The
      objectives of this study were to investigate (1) the relationship between
      duration of inflammation and the development of CVD in RA patients and (2) the
      relationship between RA disease activity over time and CVD in patients with RA.
      METHODS: RA patients with a follow-up of >=6 months in the Nijmegen early RA
      cohort without prior CVD were included. Disease activity over time was calculated
      using the time-averaged  28 joint disease activity score (DAS28) for each
      patient. Kaplan-Meier survival analysis and Cox proportional hazards regression
      were used for the analyses. RESULTS: During follow-up of the 855 patients that
      were included, 154 CV events occurred. The course of hazards over time did not
      indicate a change in the risk of CVD over the course of RA (disease duration),
      which is also reflected by the absence of a deflection in the survival curves.
      The survival distributions did not differ between patients with a disease
      duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28
      was significantly associated with CVD (p=0.002) after correction for confounders.
      CONCLUSIONS: Disease duration does not appear to independently affect the risk of
      CVD. The risk of CVD in RA patients was not increased after 10 years of disease
      duration compared with the first 10 years. Disease activity over time may
      contribute to the risk of CVD.

PMID- 24458538
TI  - Allylic functionalization of unactivated olefins with Grignard reagents.
AB  - New advances in the functionalization of unactivated olefins with carbon
      nucleophiles have provided more efficient and practical approaches to convert
      inexpensive starting materials into valuable products. Recent examples have been
      reported with stabilized carbon nucleophiles, tethered carbon nucleophiles,
      diazoesters, and trifluoromethane donors. A general method for functionalizing
      olefins with aromatic, aliphatic, and vinyl Grignard reagents was developed. In a
      one-pot process, olefins are oxidized by a commercially available reagent to
      allylic electrophiles, which undergo selective copper-catalyzed allylic
      alkylation with Grignard reagents. Products are formed in high yield and with
      high regioselectivity. This was utilized to synthesize a series of skipped
      dienes, a class of compounds that are prevalent in natural products and are
      difficult to synthesize by known allylic alkylation methods. 

PMID- 24458540
TI  - Exploring the perspectives of potential consumers and healthcare professionals on
      the readability of a package insert: a case study of an over-the-counter
      medicine.
AB  - PURPOSE: To explore and compare the opinions of physicians, pharmacists and
      potential users on the readability of a package insert of an over-the-counter
      medicine. METHODS: Exploratory study based on the administration of a semi-open
      questionnaire. This instrument was developed according to the readability
      guideline of the European Medicine Agency (EMA) and used to evaluate
      participants' accessibility to, and comprehensibility of, the package insert for
      diclofenac 12.5 mg tablets. Sixty-three participants were recruited from the
      Lisbon region and enrolled in three groups: physicians (Dg), pharmacists (Pg) and
      potential consumers (PCg), with a minimum of 20 participants each. RESULTS:
      Almost all (85 %) of the 20 PCg participants were educated above the 9th grade,
      although the majority of them (95 %) referred to, at least, one package insert
      interpretation issue, mainly related to the comprehension of technical terms.
      Amongst other differences between the groups, the Pg participants (n = 22)
      obtained a significantly less favourable opinion regarding the layout of the
      titles. Furthermore, the Pg and Dg (n = 21) participants proposed technical
      enhancements, such as the use of a table to explain the posology, precautions in
      case of renal failure, or the recommendation to take the tablets with meals.
      CONCLUSIONS: Differences in the way of using the diclofenac tablets are expected,
      considering the comprehension dissimilarities between health professionals and
      potential consumers. The package insert of diclofenac 12.5 mg could be enhanced
      for safer use. Regarding the readability assessment of this package insert, the
      method proposed in the EMA guidelines might not be as effective as expected.
      Future research is advisable.

PMID- 24458539
TI  - Metabolic implication of tumor:stroma crosstalk in breast cancer.
AB  - The metabolic properties of cancer cells significantly differ from those of
      normal cells. In particular, cancer cells are largely dependent on aerobic
      glycolysis, a phenomenon that has been exploited clinically by using labelled
      glucose for positron emission tomography imaging. Importantly, cancer-associated
      alterations in metabolism are not merely due to the resulting response to cell
      proliferation and survival. Indeed, direct metabolic regulation could be driven
      by tumor oncogenes and/or suppressors, as demonstrated in several solid tumors,
      including breast cancer. Despite the fact that most breast cancer studies have
      focused on the intrinsic characteristics of breast tumor cells, it is now widely
      accepted that tumor microenvironment plays an important role in defining and
      reprogramming cancer cell metabolism. Tumor:stroma crosstalk, as well as
      inflammatory cues, concurs to outlining the cancer metabolism, impact on cancer
      aggressiveness and ultimately on patient survival and therapeutic responses. The
      aim of this review is to (i) gather the most recent data regarding the metabolic
      alterations in breast cancer, (ii) describe the role of tumor microenvironment in
      breast cancer cell metabolic reprogramming, and (iii) contemplate how targeting
      metabolic pathways aberrantly activated in breast cancer could help current
      therapeutic regimens. 

PMID- 24458541
TI  - Challenges in collecting pharmacokinetic and pharmacodynamic information in an
      intensive care setting: PK/PD modelling of clazosentan in patients with
      aneurysmal subarachnoid haemorrhage.
AB  - PURPOSE: This paper describes the pharmacokinetic/pharmacodynamic modelling of
      clazosentan in patients with aneurysmal subarachnoid haemorrhage (aSAH), and the
      impact of collecting data in an intensive care unit (ICU) setting. Factors
      influencing data quality, analysis, and interpretation are provided with
      recommendations for future clinical studies in ICU settings. METHODS: CONSCIOUS-2
      was a phase III study involving 1,157 patients with aSAH. Secured by surgical
      clipping, patients were infused with clazosentan or placebo for up to 14 days
      post-aSAH. Clazosentan exposure relationships with vital signs, QT intervals, and
      AST/ALT values as well as efficacy and safety endpoints were characterised using
      population PK/PD and logistic regression models. RESULTS: Clazosentan clearance
      was influenced by age, sex, Asian origin, and disease status at baseline, and
      increased with time. Volume of distribution showed a sex difference. Exposure had
      no relationship with any efficacy endpoint or ALT/AST values, but was related to
      the increasing probability of lung complications. Blood pressure decreased
      proportionally to clazosentan concentrations, and the presence of clazosentan was
      associated with QT interval increases. Implausible values in the concentration
      data reflect the specific ICU challenges, possibly arising from PK sampling from
      the infusion arm or haemodilution. CONCLUSIONS: Population PK/PD modelling of
      CONCIOUS-2 data provided clinically relevant knowledge about various effects of
      clazosentan in the aSAH patient population in a real clinical setting. The
      quality of data and analyses could be improved by the collection of additional
      data and stricter training of study personnel. Differences in clinical practice
      between sites and geographical regions are more challenging to overcome.

PMID- 24458542
TI  - Potentially inappropriate prescribing to the elderly: comparison of new protocol
      to Beers criteria with relation to hospitalizations for ADRs.
AB  - PURPOSE: Screening tools for detecting potentially inappropriate medications
      (PIMs) represent an important way to assess drug prescribing in the elderly.
      Recently, we introduced a new comprehensive tool to detect both PIMs and
      clinically important drug-drug interactions (DDI). The aim of the study was to
      assess the applicability of the new tool. METHODS: The new tool was used to
      detect PIMs and DDI and to assess their relation to morbidity and hospital
      admissions. It was also compared to the widely used Beers criteria. The study
      population included 454 consecutive patients aged >=65 years who were acutely
      admitted to the Department of Internal Medicine of the University Hospital of
      Osijek. The Naranjo protocol was used to analyze the causal relationship between
      a drug and an adverse event. RESULTS: According to the new protocol, 44 %
      patients were taking PIMs, while 33 % patients were taking drugs with potentially
      serious DDIs. In 11 % of the overall number of patients, the cause of admission
      was adverse drug reaction (ADR), and among contributing drugs, 44 % were
      potentially inappropriate according to our protocol. Gastrointestinal bleeding
      was the most common diagnosis causing ADR-associated admission, and in 72 %
      cases, either PIM or a potentially serious DDI was involved. CONCLUSION: The new
      Croatian tool detected a high number of patients taking PIMs and/or having
      potentially important drug-drug interactions. The tool also detected almost half
      of the drugs contributing to ADR-associated admission. We expect the tool to be
      useful in prescription evaluation for the elderly inpatient and outpatient
      population.

PMID- 24458543
TI  - Does cognitive behaviour therapy for insomnia reduce clinical levels of fatigue,
      anxiety and depression in cancer patients?
AB  - OBJECTIVES: This secondary analysis of data from a randomised controlled trial
      explores associations between common symptom clusters and evaluates pre-treatment
      to post-treatment changes in clinical levels of these symptoms following
      cognitive behaviour therapy for insomnia (CBT-I). METHODS: Baseline data from 113
      participants with insomnia were explored to establish rates of and associations
      between clinical levels of fatigue, anxiety and depression across the sample.
      Effects of CBT-I on this symptom cluster were also explored by examining changes
      in pre-treatment to post-treatment levels of fatigue, anxiety and depression.
      RESULTS: At baseline, the most common symptom presentation was insomnia +
      fatigue, and 30% of the sample reported at least three co-morbid symptoms. Post
      CBT, the number of those experiencing clinical insomnia and clinical fatigue
      decreased. There were no changes in anxiety rates from baseline to post-treatment
      in the CBT group and modest reductions in rates of those with clinical
      depression. Seven individuals (9.6%) from the CBT group were completely symptom
      free at post-treatment compared with 0% from the treatment as usual condition.
      Chi-square analysis revealed a significant relationship between group allocation
      and changes in symptoms of insomnia and fatigue. No such relationship was found
      between group allocation and mood variables. CONCLUSIONS: These findings confirm
      the high rate of symptom co-morbidities among cancer patients and highlight
      strong associations between sleep and fatigue. CBT-I appears to offer generalised
      benefit to the symptom cluster as a whole and, specifically, is effective in
      reducing fatigue, which exceeded clinical cut-offs prior to implementation of the
      intervention. This has implications for the diagnosis/management of common
      symptoms in cancer patients.

PMID- 24458544
TI  - Old proteins and the Achilles heel of mass spectrometry. The role of proteomics
      in the etiology of human cataract.
AB  - Proteomics may have enabled the root cause of a major human-blinding condition,
      age-related cataract, to be established. Cataract appears to result from the
      spontaneous decomposition of long-lived macromolecules in the human lens, and
      recent proteomic analysis has enabled both the particular crystallins, and the
      specific sites of amino acid modification within each polypeptide, to be
      identified. Analysis of proteins from cataract lenses has demonstrated that there
      are key sites on some structural proteins that show a consistently greater degree
      of deterioration than age-matched normal lenses. Proteomic analysis, using MS,
      revealed that the most abundant posttranslational modification of aged lens
      proteins is racemization. This is somewhat ironic, since structural isomers can
      be viewed as the "Achilles heel" of MS and there are typically few, if any,
      differences in the MS/MS spectra of tryptic peptides containing one d-amino acid.
      It is proposed that once a certain level of spontaneous PTM at key sites occurs,
      that protein-protein interactions are disrupted, and binding of complexes to cell
      membranes takes place that impairs cell-to-cell communication. These findings may
      apply more widely to age-related human diseases, in particular where the
      deterioration of long-lived proteins is a crucial component in the etiology. 

PMID- 24458545
TI  - Association between glycated hemoglobin and health utility for Type 1 diabetes.
AB  - OBJECTIVES: Cost-effectiveness models for diabetes link glycated hemoglobin
      (HbA1c) to diabetes-related complications. Independent of diabetes-related
      complications, there is little known on the association between HbA1c and health
      utility scores. This link can alter the cost effectiveness of interventions
      designed to improve HbA1c. The cross-sectional relationship between HbA1c and
      health utility scores in adult type 1 diabetes patients was estimated after
      adjusting for diabetes-related complications. METHODS: The EuroQoL-5 dimension
      (EQ-5D) questionnaire and an ad hoc survey requesting demographic information and
      adherence to glucose monitoring therapies was administered to adult type 1
      diabetes patients during a clinic visit and combined with clinical medical record
      data. Health utility scores were derived using the US time-tradeoff valuation of
      the EQ-5D. Linear regression was used to estimate the relationship between HbA1c
      and utility, adjusting for treatments, demographics, and diabetes-related
      complications. RESULTS: Among 176 patients, mean (standard deviation [SD]) age
      was 38 (12.2) years, duration of disease was 22 (12.1) years, and number of
      chronic conditions other than type 1 diabetes was 2.7 (2.0). Unadjusted mean (SD)
      utility was 0.94 (0.09) for those with HbA1c levels <7 % (n = 54), 0.89 (0.15)
      for those with HbA1c >= 7 % (n = 122), and 0.91 (0.14) for all patients. After
      adjustment, a 1 % absolute increase in HbA1c was associated with a disutility of 
      0.03 (95 % confidence interval [CI] -0.049, -0.006). CONCLUSIONS: Findings
      suggest that, after adjusting for diabetes-related complications, higher HbA1c
      levels are associated with a significant health disutility. Pending additional
      data from longitudinal studies, these findings could be used in cost
      effectiveness evaluations of type 1 diabetes interventions that impact HbA1c.

PMID- 24458546
TI  - Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by
      which they impact on pancreatic tumorigenesis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) still ranking 4th in the order of fatal
      tumor diseases is characterized by a profound tumor stroma with high numbers of
      tumor-associated macrophages (TAMs). Driven by environmental factors, monocytes
      differentiate into M1- or M2-macrophages, the latter commonly regarded as being
      protumorigenic. Because a detailed analysis of TAMs in human PDAC development is
      still lacking, freshly isolated PDAC-derived TAMs were analyzed for their
      phenotype and impact on epithelial-mesenchymal-transition (EMT) of benign (H6c7)
      and malignant (Colo357) pancreatic ductal epithelial cells. TAMs exhibited
      characteristics of M1-macrophages (expression of HLA-DR, IL-1beta, or TNF-alpha)
      and M2-macrophages (expression of CD163 and IL-10). In the presence of TAMs,
      H6c7, and Colo357 cells showed an elongated cell shape along with an increased
      expression of mesenchymal markers such as vimentin and reduced expression of
      epithelial E-cadherin. Similar to TAMs, in vitro generated M1- and M2-macrophages
      both mediated EMT in H6c7 and Colo357 cells. M1-macrophages acquired M2
      characteristics during coculture that could be prevented by GM-CSF treatment.
      However, M1-macrophages still potently induced EMT in H6c7 and Colo357 cells
      although lacking M2-characteristics. Overall, these data demonstrate that TAMs
      exhibit anti- as well as proinflammatory properties that equally contribute to
      EMT induction in PDAC initiation and development. 

PMID- 24458547
TI  - Determination of mazindol in human oral fluid by high performance liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - Brazil is one of the countries most affected by abuse of stimulant medications by
      professional drivers, especially fenproporex, amfepramone and mazindol. Even
      though their sale is banned, they can be found in illegal markets, such as those
      located on the country's borders. The use of oral fluid to monitor drug levels
      has many advantages over plasma and urine because it is noninvasive, easier to
      collect and more difficult to adulterate. The aim of this study was to develop
      and validate a sensitive and specific method to quantify mazindol in human oral
      fluid by liquid chromatography-mass spectrometry (LC-MS). The LC system consisted
      of an LC-MS system operated in selected ion monitoring mode. The mobile phase was
      composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow
      rate of 1.0 mL/min and propranolol was used as internal standard. Total running
      time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method
      exhibited good linearity within the 0.2-20 ng/mL range (r = 0.9987). A rapid,
      specific, sensitive, linear, precise and accurate method was developed for
      determination of mazindol in human oral fluid according to European Medicines
      Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid
      of professional drivers.

PMID- 24458548
TI  - Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with
      chromosome 16p11.2 rearrangement.
AB  - The typical chromosome 16p11.2 rearrangements are estimated to occur at a
      frequency of approximately 0.6% of all samples tested clinically and have been
      identified as a major cause of autism spectrum disorders, developmental delay,
      behavioral abnormalities, and seizures. Careful examination of patients with
      these rearrangements revealed association with abnormal head size, obesity,
      dysmorphism, and congenital abnormalities. In this report, we extend this list of
      phenotypic abnormalities to include scoliosis and vertebral anomalies. We present
      detailed characterization of phenotypic and radiological data of 10 new patients,
      nine with the 16p11.2 deletion and one with the duplication within the
      coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb.
      We discuss the phenotypical and radiological findings in our patients and review
      5 previously reported patients with 16p11.2 rearrangement and similar skeletal
      abnormalities. Our data suggest that patients with the recurrent 16p11.2
      rearrangement have increased incidence of scoliosis and vertebral anomalies.
      However, additional studies are required to confirm this observation and to
      establish the incidence of these anomalies. We discuss the potential implications
      of our findings on the diagnosis, surveillance and genetic counseling of patients
      with 16p11.2 rearrangement.

PMID- 24458549
TI  - Long-term graft outcome after renal arterial reconstruction during living related
      kidney transplantation.
AB  - BACKGROUND/OBJECTIVES: The aim of this retrospective study was to evaluate the
      repair of vascular variations/pathologies in living donor kidney transplantations
      in a single centre over a 15-year period. METHODS: Between 01/1997 and 05/2012,
      338 living donor renal transplantations were performed in the Department for
      Endovascular and Vascular Surgery, University of Dusseldorf, Germany. Twenty-four
      of them showed disorders, like multiple renal arteries (MRA), atherosclerotic
      stenosis or fibromuscular dysplasia (FMD) needing vascular repair before
      transplantation. RESULTS: Mean age of donors was 51 +/- 11.2, in recipient's 44
      +/- 13.9 years. In seven transplantations, renal artery (RA) repair was performed
      because of MRA. Atherosclerotic stenosis of the RA was apparent in 12 cases
      needing a repair with disobliteration. FMD was the reason in five
      transplantations for vascular repair. Complications like renal vessel thrombosis,
      lymphocele, heamorrhage, distal urinary leakage and ureteral obstruction was not
      significantly associated with RA reconstruction. Comparison of renal function in
      kidneys with reconstructed RA compared with kidneys without vascular repair
      showed no significant difference in primary function and serum creatinine up to
      the first year after transplantation. Mean follow-up was 75.6 +/- 48.1 months.
      The 5-year graft survival rate for kidneys with RA repair was 88.5 vs. 93.4 %
      without reconstruction. CONCLUSIONS: We could show that RA pathologies, suitable
      repaired, are not a contraindication for transplantation with acceptable 5-year
      graft-survival rates.

PMID- 24458550
TI  - Germline CBL mutation associated with a noonan-like syndrome with primary
      lymphedema and teratoma associated with acquired uniparental isodisomy of
      chromosome 11q23.
AB  - Germline mutations in the gene CBL (Casitas B-lineage lymphoma), involved in the
      RAS-MAPK signaling pathway, have been found as a rare cause of the neuro-cardio
      facial-cutaneous syndromes. Somatically acquired homozygous CBL mutations were
      initially identified in association with myeloproliferative disorders,
      particularly juvenile myelomonocytic leukemia (JMML). We describe a girl with a
      Noonan-like phenotype of bilateral ptosis, lymphedema of the lower limbs and
      moderate intellectual disability, due to a de novo heterozygous mutation in CBL.
      She developed an ovarian mixed germ cell/teratoma with later occurrence of mature
      liver, omental, and ovarian teratomas. Copy neutral loss of heterozygosity for
      the CBL mutation due to acquired segmental uniparental disomy of 11q23 was
      observed in three teratomas, suggesting a specific association of CBL mutations
      in germ cell tumor predisposition.

PMID- 24458551
TI  - Quantitative analysis of the debonding structure of soft adhesives.
AB  - We experimentally investigate the growth dynamics of cavities nucleating during
      the first stages of debonding of three different model adhesives. The material
      properties of these adhesives range from a more liquid-like material to a soft
      viscoelastic solid and are carefully characterized by small strain oscillatory
      shear rheology as well as large strain uniaxial extension. The debonding
      experiments are performed on a probe tack set-up. Using high contrast images of
      the debonding process and precise image analysis tools, we quantify the total
      projected area of the cavities, the average cavity shape and growth rate and link
      these observations to the material properties. These measurements are then used
      to access corrected effective stress and strain curves that can be directly
      compared to the results from the uniaxial extension. 

PMID- 24458552
TI  - Ordering kinetics in liquid crystals with long-ranged interactions.
AB  - We present the results from comprehensive Monte Carlo (MC) simulations of
      ordering kinetics in d = 2 liquid crystals (LCs). Our LC system is described by
      the two-component Lebwohl-Lasher model with long-ranged interactions, V(r) ~ r(
      n). We find that systems with n >= 2 show the same dynamical behavior as the
      nearest-neighbor case (n = infinity). This contradicts available theoretical
      predictions.

PMID- 24458553
TI  - Ratchet rotation of a 3D dimer on a vibrating plate.
AB  - This work studies the dynamics of a 3D dimer bouncing upon a horizontal plate
      undergoing a vertical harmonic vibration. Despite complex interactions within the
      system due to impacts and friction, numerical simulation shows that, under
      certain conditions prescribed for the dynamics, the center of mass of the dimer,
      when projected onto a horizontal plane, will follow a circular orbit. The
      phenomenon is like a particle under Coulomb friction performing a ratchet motion
      that rotates around. Investigations further reveal that the dimer dynamics bear
      some typical characteristics of a nonlinear system, including sensitivity to the
      initial conditions and bifurcation behaviors related to the physical parameters
      of the dynamics. Our results indicate that the coefficient of restitution and the
      plate's vibration intensity play critical roles in exciting the circular orbit,
      while the dimer's geometry and the vibration frequency mainly influence the
      trajectory characteristics. These findings may help understand transport
      mechanisms underlying systems of granular matter with anisotropic particles. 

PMID- 24458554
TI  - Rhodium(III)-catalyzed C-H activation and indole synthesis with hydrazone as an
      auto-formed and auto-cleavable directing group.
AB  - An efficient, practical, and external-oxidant-free indole synthesis from readily
      available aryl hydrazines was developed, by using hydrazone as a directing group
      for Rh(III)-catalyzed C-H activation and alkyne annulation. The hydrazone group
      was formed by in situ condensation of hydrazines and C=O source, whereas its N-N
      bond was served as an internal oxidant, for which we termed it as an auto-formed
      and auto-cleavable directing group (DG(auto)). This method needs no step for pre
      installation and post-cleavage of the directing group, making it a quite easily
      scalable approach to access unprotected indoles with high step economy. The
      DG(auto) strategy was also applicable for isoquinoline synthesis. In addition,
      synthetic utilities of this chemistry for rapid assembly of pi-extended nitrogen
      doped polyheterocycles and bioactive molecules were demonstrated.

PMID- 24458555
TI  - Biomass and energy in France; some aspects of research and development.

PMID- 24458556
TI  - Loose association of ribulose 1,5-bisphosphate carboxylase/oxygenase with
      chloroplast thylakoid membranes.
AB  - The intra-chloroplastic distribution of ribulose 1,5-bisphosphate
      carboxylase/oxygenase (RuBisCO) between thylakoid membranes and stroma was
      studied by determining the enzyme activities in the two fractions, obtained by
      the rapid centrifugation of hypotonically disrupted chloroplast preparations of
      spinach and pea leaf tissues. The membrane-associated form of RuBisCO was found
      to increase in proportion to the concentration of MgCl2 in the disrupting medium;
      with 20 mM MgCl2 approximately 20% of the total RuBisCO of spinach chloroplasts
      and 10% of that of pea chloroplasts became associated with thylakoid membranes.
      Once released from membranes in the absence of MgCl2, addition of MgCl2 did not
      cause reassociation of the enzyme. The inclusion of KCl in the hypotonic
      disruption buffer also caused the association of RuBisCO with membranes; however,
      up to 30 mM KCl, only minimal enzyme activities could be detected in the
      membranes, whereas above 40 mM KCl there was a sharp increase in the membrane
      associated form of the enzyme.Higher concentrations of chloroplasts during the
      hypotonic disruption, as well as addition of purified preparations of RuBisCO to
      the hypotonic buffer, resulted in an increase of membrane-associated activity.
      Therefore, the association of the enzyme with thylakoid membranes appears to be
      dependent on the concentration of RuBisCO. P-glycerate kinase and aldolase also
      associated to the thylakoid membranes but NADP-linked glyceraldehyde-3-P
      dehydrogenase did not. The optimal conditions for enzyme association with the
      thylakoid membranes were examined; maximal association occurred at pH 8.0. The
      association was temperature-insensitive in the range of 4 degrees  to 25 degrees 
      C. RuBisCO associated with the thylakoid membranes could be gradually liberated
      to the soluble form upon shaking in a Vortex mixer at maximal speed, indicating
      that the association is loose. 

PMID- 24458557
TI  - Photoacoustic spectroscopy (PAS) and its application in photosynthesis research.

PMID- 24458558
TI  - Purified Ribulose-P2 carboxylase from wheat with high specific activity and with
      fast activation.

PMID- 24458559
TI  - Fluidity properties of isolated chloroplast thylakoid lipids.
AB  - Chloroplast thylakoid lipids have been isolated free of photosynthetic pigments
      using a combination of high performance liquid and thin layer chromatography. The
      hydrophobic fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH) has been
      incorporated into aqueous dispersions of the isolated lipids in order to
      investigate dynamic and structural properties of the resulting bilayer membranes.
      Time dependent fluorescence anisotropy decays have been measured and analysed
      assuming the wobbling-in-cone model (Kinosita et al., Biophys J 20 (1977) 289
      305). The DPH fluorescence lifetimes and the static and dynamic fluorescence
      anisotropy decay parameters for the probe in a total lipid mixture or in pure
      digalactosyldiacylglycerol (DGDG), changed in a predictable way with increasing
      temperature (10 degrees -36 degrees C). For a given temperature, it was found
      that the total lipid mixture was in general less ordered and showed greater
      dynamic motion as judged from DPH fluorescence anisotropy and compared with the
      pure DGDG system, although at 36 degrees C differences in dynamic parameters were
      less evident. Overall the results obtained emphasize the highly fluid nature of
      thylakoid membrane lipids and give a basis for investigating how intrinsic
      proteins modify structural and dynamic properties of the in vivo membrane. 

PMID- 24458560
TI  - Properties of a pigment system consisting of carotenoids and reaction centre
      pigments in chromatophores of Rhodospirillum rubrum.
AB  - A pigment system containing carotenoids and oxidised reaction centre pigments is
      present in chromatophores of Rhodospirillum rubrum and this pigment system may
      cause fluorescence quenching when a still unidentified chromatophore component is
      in its oxidised state. Besides by its action spectrum, this pigment system is
      characterised by the time course and level of light saturation of the effect. The
      quenching of bacteriochlorophyll fluorescence is abolished when the permeability
      of the chromatophore membranes is affected. The quenching effect is correlated
      with a reversible absorption decrease of B 880. A possible function for this
      pigment system is discussed. 

PMID- 24458561
TI  - Aerosol emitters disrupt codling moth, Cydia pomonella, competitively.
AB  - BACKGROUND: Isomate((r)) CM MIST aerosol emitters (Pacific BioControl Corp,
      Vancouver, WA) containing 36 g of codlemone, (E,E)-8,10-dodecadien-1-ol, were
      deployed at various densities in a commercial apple orchard to generate dosage
      response profiles in order to elucidate the behavioral mechanism of disruption.
      RESULTS: Moth captures decreased asymptotically as Isomate((r)) CM MIST densities
      increased. Data fitting to Miller-Gut and Miller-de Lame plots yielded straight
      lines, with positive and negative slopes respectively. Catch of male moths
      decreased from 28 trap(-1) in the control to 0.9 trap(-1) at the highest emitter
      density. Disruption of >90% was realized at emitter densities greater than 5
      units ha(-1) . CONCLUSION: The resulting set of profiles explicitly matched the
      predictions for competitive rather than non-competitive disruption. Thus, these
      devices probably disrupt by inducing false-plume following rather than by
      camouflaging traps and females. The use of 5 MIST units ha(-1) would be necessary
      to achieve the same level of codling moth control provided by a standard
      pheromone treatment with passive reservoir dispensers. The need for only a few
      aerosol emitters, 2.5-5 units ha(-1) , mitigates the cost of labor required to
      hand-apply hundreds of passive reservoir dispensers; however, a potential
      weakness in using this technology is that the low deployment density may leave
      areas of little or no pheromone coverage, where mate finding may occur. This
      technology is likely to benefit substantially from treatment of large contiguous
      blocks of crop.

PMID- 24458562
TI  - Three new sterigmatocystin analogues from marine-derived fungus Aspergillus
      versicolor MF359.
AB  - During the systematic screening of active compounds from marine-derived fungi,
      the extract of a strain of Aspergillus versicolor MF359 isolated from a marine
      sponge of Hymeniacidon perleve was identified for detailed chemical
      investigation. Three new secondary metabolites, named hemiacetal sterigmatocystin
      (1), acyl-hemiacetal sterigmatocystin (2), and 5-methoxydihydrosterigmatocystin
      (3), together with a known compound, aversin (4), were characterized. 1
      represents a first structure of sterigmatocystin hemiacetal from nature. The
      antibacterial activities of these identified compounds were evaluated against
      Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus
      subtilis, and Pseudomonas aeruginosa. Compound 3 showed activity against S.
      aureus and B. subtilis with MIC values of 12.5 and 3.125 MUg/mL, respectively. 

PMID- 24458563
TI  - Synthetic promoter libraries for Corynebacterium glutamicum.
AB  - The ability to modulate gene expression is an important genetic tool in systems
      biology and biotechnology. Here, we demonstrate that a previously published easy
      and fast PCR-based method for modulating gene expression in lactic acid bacteria
      is also applicable to Corynebacterium glutamicum. We constructed constitutive
      promoter libraries based on various combinations of a previously reported C.
      glutamicum -10 consensus sequence (gngnTA(c/t)aaTgg) and the Escherichia coli -35
      consensus, either with or without an AT-rich region upstream. A promoter library
      based on consensus sequences frequently found in low-GC Gram-positive
      microorganisms was also included. The strongest promoters were found in the
      library with a -35 region and a C. glutamicum -10 consensus, and this library
      also represents the largest activity span. Using the alternative -10 consensus
      TATAAT, which can be found in many other prokaryotes, resulted in a weaker but
      still useful promoter library. The upstream AT-rich region did not appear to
      affect promoter strength in C. glutamicum. In addition to the constitutive
      promoters, a synthetic inducible promoter library, based on the E. coli lac
      promoter, was constructed by randomizing the 17-bp spacer between -35 and -10
      consensus sequences and the sequences surrounding these. The inducible promoter
      library was shown to result in beta-galactosidase activities ranging from 284 to
      1,665 Miller units when induced by IPTG, and the induction fold ranged from 7-59.
      We find that the synthetic promoter library (SPL) technology is convenient for
      modulating gene expression in C. glutamicum and should have many future
      applications, within basic research as well as for optimizing industrial
      production organisms.

PMID- 24458564
TI  - Carotenoid production from n-alkanes with a broad range of chain lengths by the
      novel species Gordonia ajoucoccus A2(T).
AB  - A novel diesel-degrading bacterial strain, A2(T), was isolated from soil that was
      heavily contaminated with oil. Based on phenotypic, phylogenetic, and DNA
      analyses, strain A2(T) was identified as a novel species of the genus Gordonia
      and named Gordonia ajoucoccus A2(T) (KCTC 11900BP and CECT8382). G. ajoucoccus
      A2(T) is able to synthesize carotenoids and produces mainly gamma-carotene and
      keto-gamma-carotene. G. ajoucoccus A2(T) is also capable of assimilating n
      alkanes with a broad range of chain lengths (C6, C8-C25). Batch culture of G.
      ajoucoccus A2(T) in a bioreactor containing 1 % (v/v) hexadecane or 1 % (v/v)
      commercial diesel yielded 25 mg L-1 and 2.6 mg L-1 of carotenoids, respectively.
      Gas chromatography/mass spectrometry (GC-MS) analysis of hexadecane and hexane
      degradation metabolites suggested that G. ajoucoccus A2(T) may possess a terminal
      oxidation pathway that allows it to utilize n-alkanes and hexane as carbon and
      energy sources. G. ajoucoccus A2(T) could therefore serve as a good model system
      for understanding microbial n-alkane degradation pathways. Additionally, the
      metabolic capabilities of G. ajoucoccus A2(T) suggest potential biotechnological
      applications, such as the bioproduction of carotenoids from industrial discharge
      or other sources of n-alkanes.

PMID- 24458565
TI  - Hepatitis B virus surface antigen as delivery vector can enhance Chlamydia
      trachomatis MOMP multi-epitope immune response in mice.
AB  - Chlamydia trachomatis is the leading cause of sexually transmitted infections
      worldwide. There is currently no commercially available vaccine against C.
      trachomatis. Major outer membrane protein (MOMP) of C. trachomatis is considered
      to be an ideal candidate for prophylactic vaccine. We designed a MOMP multi
      epitope containing T- and B-cell epitope-rich peptides and developed hepatitis B
      surface antigen (HBsAg) as antigen delivery vehicle. In order to study the
      immunogenicity and efficacy of the candidate vaccine in a murine model of
      chlamydial genital infection, we engineered a recombinant plasmid expressing
      HBsAg and MOMP multi-epitope genes. Results of reverse transcription polymerase
      chain reaction and immunofluorescence assay revealed successful expression of the
      recombinant HBsAg/MOMP multi-epitope gene at both the transcription and
      translation levels. Intramuscular administration in mice was able to elicit not
      only antibodies against Chlamydia and HBsAg but also cytotoxic T lymphocyte
      activity against Chlamydia. In addition, mice inoculated with the rHBsAg were
      highly resistant to C. trachomatis genital infection. The rHBsAg DNA with MOMP
      multi-epitope appended at the C terminus of the HBsAg stimulated a stronger
      immune response and protective response than that appended at the N terminus.
      Together, our results suggested that use of a recombinant HBsAg encoding the MOMP
      multi-epitope could be a powerful approach to developing a safe and immunogenic
      C. trachomatis vaccine. 

PMID- 24458566
TI  - Seamless integration of dose-response screening and flow chemistry: efficient
      generation of structure-activity relationship data of beta-secretase (BACE1)
      inhibitors.
AB  - Drug discovery is a multifaceted endeavor encompassing as its core element the
      generation of structure-activity relationship (SAR) data by repeated chemical
      synthesis and biological testing of tailored molecules. Herein, we report on the
      development of a flow-based biochemical assay and its seamless integration into a
      fully automated system comprising flow chemical synthesis, purification and in
      line quantification of compound concentration. This novel synthesis-screening
      platform enables to obtain SAR data on b-secretase (BACE1) inhibitors at an
      unprecedented cycle time of only 1 h instead of several days. Full integration
      and automation of industrial processes have always led to productivity gains and
      cost reductions, and this work demonstrates how applying these concepts to SAR
      generation may lead to a more efficient drug discovery process. 

PMID- 24458567
TI  - Parenting stress as a mediator of parents' negative mood state and behavior
      problems in children with newly diagnosed cancer.
AB  - OBJECTIVE: The aim was to investigate the influence of parents' negative mood
      state and parenting stress on behavior in children with newly diagnosed cancer.
      METHODS: A total of 123 parents (n=58 fathers, n=65 mothers) of 67 children with
      newly diagnosed cancer completed three questionnaires separately at the same time
      measuring parents' negative mood state, parenting stress, and child behavior
      problems. RESULTS: Parents' negative mood state was weakly correlated to more
      child behavior problems (r=0.31, p<0.01), and higher levels of parenting stress
      were strongly correlated to more child behavior problems (r=0.61, p<0.01).
      Mediation analyses indicated that the relationship between parents' negative mood
      state and child behavior problems (c=0.29, p=0.02 (fathers); c=0.25, p=0.04
      (mothers)) became non-significant after mediating for parenting stress (c'=0.003,
      p=0.98 (fathers); c'=0.10, p=0.42 (mothers)). The indirect effect of parents'
      negative mood state and child behavior problems was only significant for fathers
      (95% CI [0.12; 0.51]), indicating that parenting stress mediates the effect
      between fathers' negative mood state and child behavior problems. CONCLUSIONS:
      This is the first study to demonstrate the mediational role of parenting stress
      in fathers of a child with newly diagnosed cancer.

PMID- 24458568
TI  - The insulin-like growth factor 1 receptor causes acquired resistance to erlotinib
      in lung cancer cells with the wild-type epidermal growth factor receptor.
AB  - Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy
      often provides a dramatic response in lung cancer patients with EGFR mutations.
      In addition, moderate clinical efficacy of the EGFR-TKI, erlotinib, has been
      shown in lung cancer patients with the wild-type EGFR. Numerous molecular
      mechanisms that cause acquired resistance to EGFR-TKIs have been identified in
      lung cancers with the EGFR mutations; however, few have been reported in lung
      cancers with the wild-type EGFR. We used H358 lung adenocarcinoma cells lacking
      EGFR mutations that showed modest sensitivity to erlotinib. The H358 cells
      acquired resistance to erlotinib via chronic exposure to the drug. The H358
      erlotinib-resistant (ER) cells do not have a secondary EGFR mutation, neither MET
      gene amplification nor PTEN downregulation; these have been identified in lung
      cancers with the EGFR mutations. From comprehensive screening of receptor
      tyrosine kinase phosphorylation, we observed increased phosphorylation of insulin
      like growth factor 1 receptor (IGF1R) in H358ER cells compared with parental H358
      cells. H358ER cells responded to combined therapy with erlotinib and NVP-AEW541,
      an IGF1R-TKI. Our results indicate that IGF1R activation is a molecular mechanism
      that confers acquired resistance to erlotinib in lung cancers with the wild-type
      EGFR. 

PMID- 24458569
TI  - An amnion implantation hypothesis: a conceptual framework for mechanism-based
      studies of amnion adhesion.

PMID- 24458571
TI  - A rapid, simple and reliable HPLC-triple quadrupole tandem mass spectrometer
      method for a simultaneous quantification of irinotecan and its active metabolite
      7-ethyl-10-hydroxycamptothecin (SN38) in mouse plasma.
AB  - A simple, fast and reliable high-performance liquid chromatography-triple
      quadrupole mass spectrometry method (HPLC-MS/MS method) was developed, validated
      and used for the simultaneous quantification of irinotecan and 7-ethyl-10
      hydroxycamptothecin (SN38) in heparinized mouse plasma. Camptothecin was used as
      the internal standard. A single-step protein precipitation without evaporation
      and reconstitution steps was adopted as sample processing method. Our
      bioanalytical method was validated in compliance with the guidelines from the
      European Medicines Agency. The lower limit of quantification for both irinotecan
      and SN38 was 5 ng/mL. The calibration curves for both analytes fitted to a 1/x(2)
      weighted linear regression model and ranged from 5 to 1000 ng/mL. The intra-run
      and inter-run precisions were within 8.6%, and the intra-run and inter-run
      accuracies were within 96.4-103.9%. Our validated bioanalytical method was
      successfully applied to the pharmacokinetic study in mice, in which 4 mg/kg
      irinotecan was intraperitoneally injected.

PMID- 24458570
TI  - Aberrant glycosylation in the human trabecular meshwork.
AB  - PURPOSE: To determine the difference in protein glycosylation and glycosylation
      enzyme levels between glaucomatous and control trabecular meshwork (TM).
      EXPERIMENTAL DESIGN: Glaucomatous and normal donor (n = 12 each) TM tissues,
      lectin fluorescence, fluorophore-assisted carbohydrate analyses, and quantitative
      MS were used to determine the glycosylation levels. Primary TM cells and
      glycosylation inhibitors were used to determine their effect on cell shape and
      motility. RESULTS: In contrast to elevated levels of glycoproteins determined by
      lectin fluorescence, simultaneous hyper- and hypo-glycosylation in glaucomatous
      TM was revealed by fluorophore-assisted carbohydrate analyses. Analyses of
      enzymes showed elevation of beta-glycosidase 1 and decrease in
      galactosyltransferase family 6 domain containing protein 1 in the glaucomatous
      TM. Quantitative MS identified select protein level changes between glaucomatous
      and normal TM. Primary TM cells were treated with inhibitors to elicit hypo
      glycosylation, which affected cell shape, motility, and fluorescent tracer
      transport across a layer of TM cells. CONCLUSIONS AND CLINICAL RELEVANCE: Global
      protein glycosylation is aberrant in glaucomatous TM compared to controls. The
      results presented here suggest that the alteration in global TM protein
      glycosylation encompassing cellular and extracellular matrix proteins contributes
      to glaucoma pathology likely mediated through changes in properties of TM cells.

PMID- 24458572
TI  - Diagnosis of struma ovarii in a patient with papillary thyroid carcinoma-
      verification via 124I-PET/US fusion.

PMID- 24458573
TI  - A risk-adapted approach using US features and FNA results in the management of
      thyroid incidentalomas identified by 18F-FDG PET.
AB  - PURPOSE: To assess the risk of malignancy of thyroid incidentalomas found on 18F
      FDG PET/CT by US features and cytologic results, and to evaluate the clinical
      usage of a combination of US features and cytology for post-FNA management of
      thyroid incidentalomas on 18F-FDG PET/CT. MATERIALS AND METHODS: From September
      2006 to December 2008, 132 patients with 134 thyroid incidentalomas detected on
      18F-FDG PET/CT who had undergone US and US-FNA were included in this study. We
      evaluated the malignancy rate of thyroid incidentalomas in different subgroups
      subdivided by US features and US-FNA cytology results. Several variables were
      compared between the benign and malignant group. RESULTS: The risk of malignancy
      was 58.2 % (78/132) in thyroid incidentalomas on 18F-FDG PET/CT. Age, gender, and
      tumor size were not significantly different between the malignant and benign
      group.  Malignancy rate of thyroid incidentalomas was significantly higher in the
      suspicious malignant (88.9 %) than in the probably benign group (11.3 %) on US (p
      < 0.001). Malignancy rates were high in thyroid nodules with "malignancy",
      "suspicious for malignancy", or "follicular neoplasm" on cytologic results,
      regardless of US features. However, malignancy rates of thyroid incidentalomas
      with "unsatisfactory" or "benign" results on cytology were higher in the
      suspicious malignant (75 %, 12.5 %, respectively) than in the probably benign (0
      %) group on US.  CONCLUSIONS: This study demonstrated that the risk of malignancy
      was high in thyroid incidentalomas on 18F-FDG PET/CT even without suspicious US
      features. However, there was no malignancy in nodules with no suspicious US
      features and benign cytology. Based on these results, we concluded that US may
      not replace FNA in the diagnosis of PET incidentalomas, and that a follow-up may
      be considered of thyroid incidentalomas with benign cytology and no suspicious US
      features.

PMID- 24458577
TI  - 25th anniversary article: charge transport and recombination in polymer light
      emitting diodes.
AB  - This article reviews the basic physical processes of charge transport and
      recombination in organic semiconductors. As a workhorse, LEDs based on a single
      layer of poly(p-phenylene vinylene) (PPV) derivatives are used. The hole
      transport in these PPV derivatives is governed by trap-free space-charge-limited
      conduction, with the mobility depending on the electric field and charge-carrier
      density. These dependencies are generally described in the framework of hopping
      transport in a Gaussian density of states distribution. The electron transport on
      the other hand is orders of magnitude lower than the hole transport. The reason
      is that electron transport is hindered by the presence of a universal electron
      trap, located at 3.6 eV below vacuum with a typical density of ca. 3 * 1017 cm-3.
      The trapped electrons recombine with free holes via a non-radiative trap-assisted
      recombination process, which is a competing loss process with respect to the
      emissive bimolecular Langevin recombination. The trap-assisted recombination in
      disordered organic semiconductors is governed by the diffusion of the free
      carrier (hole) towards the trapped carrier (electron), similar to the Langevin
      recombination of free carriers where both carriers are mobile. As a result, with
      the charge-carrier mobilities and amount of trapping centers known from charge
      transport measurements, the radiative recombination as well as loss processes in
      disordered organic semiconductors can be fully predicted. Evidently, future work
      should focus on the identification and removing of electron traps. This will not
      only eliminate the non-radiative trap-assisted recombination, but, in addition,
      will shift the recombination zone towards the center of the device, leading to an
      efficiency improvement of more than a factor of two in single-layer polymer LEDs.

PMID- 24458578
TI  - A graphene-pure-sulfur sandwich structure for ultrafast, long-life lithium-sulfur
      batteries.

PMID- 24458579
TI  - Scalable fabrication of ambipolar transistors and radio-frequency circuits using
      aligned carbon nanotube arrays.

PMID- 24458583
TI  - Early cow's milk introduction is associated with failed personal-social
      milestones after 1 year of age.
AB  - Both the American Academy of Pediatrics (AAP) and the Institute of Medicine (IOM)
      recommend delaying the introduction of cow's milk until after 1 year of age due
      to its low absorbable iron content. We used a novel computerized decision support
      system to gather data from multiple general pediatrics offices. We asked families
      whether their child received cow's milk before 1 year of age, had a low-iron
      diet, or used low-iron formula. Then, at subsequent visits, we performed a
      modified developmental assessment using the Denver II. We assessed the effect of
      early cow's milk or a low-iron diet on the later failure of achieving
      developmental milestones. We controlled for covariates using logistic regression.
      Early cow's milk introduction (odds ratio (OR) 1.30, p = 0.012), as well as a low
      iron diet or low-iron formula (OR 1.42, p < 0.001), was associated with increased
      rates of milestone failure. Only personal-social milestones (OR 1.44, p = 0.002)
      showed a significantly higher rate of milestone failure. Both personal-social (OR
      1.42, p < 0.001) and language (OR 1.22, p = 0.009) showed higher rates of failure
      in children with a low-iron diet. CONCLUSIONS: There is an association between
      the introduction of cow's milk before 1 year of age and the rate of delayed
      developmental milestones after 1 year of age. This adds strength to the
      recommendations from the AAP and IOM to delay cow's milk introduction until after
      1 year of age.

PMID- 24458584
TI  - Would criminalising healthcare professionals for wilful neglect improve patient
      care?

PMID- 24458586
TI  - Early fetal growth and risk factors for cardiovascular disease.

PMID- 24458585
TI  - First trimester fetal growth restriction and cardiovascular risk factors in
      school age children: population based cohort study.
AB  - OBJECTIVE: To examine whether first trimester fetal growth restriction correlates
      with cardiovascular outcomes in childhood. DESIGN: Population based prospective
      cohort study. SETTING: City of Rotterdam, the Netherlands. PARTICIPANTS: 1184
      children with first trimester fetal crown to rump length measurements, whose
      mothers had a reliable first day of their last menstrual period and a regular
      menstrual cycle. MAIN OUTCOMES MEASURES: Body mass index, total and abdominal fat
      distribution, blood pressure, and blood concentrations of cholesterol,
      triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7
      6.8) years. Clustering of cardiovascular risk factors was defined as having three
      or more of: high android fat mass; high systolic or diastolic blood pressure; low
      high density lipoprotein cholesterol or high triglycerides concentrations; and
      high insulin concentrations. RESULTS: One standard deviation score greater first
      trimester fetal crown to rump length was associated with a lower total fat mass (
      0.30%, 95% confidence interval -0.57% to -0.03%), android fat mass (-0.07%, 
      0.12% to -0.02%), android/gynoid fat mass ratio (-0.53, -0.89 to -0.17),
      diastolic blood pressure (-0.43, -0.84 to -0.01, mm Hg), total cholesterol (
      0.05, -0.10 to 0, mmol/L), low density lipoprotein cholesterol (-0.04, -0.09 to
      0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk
      0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and
      weight at birth changed these effect estimates only slightly. Childhood body mass
      index fully explained the associations of first trimester fetal crown to rump
      length with childhood total fat mass. First trimester fetal growth was not
      associated with other cardiovascular outcomes. Longitudinal growth analyses
      showed that compared with school age children without clustering of
      cardiovascular risk factors, those with clustering had a smaller first trimester
      fetal crown to rump length and lower second and third trimester estimated fetal
      weight but higher weight growth from the age of 6 months onwards. CONCLUSIONS:
      Impaired first trimester fetal growth is associated with an adverse
      cardiovascular risk profile in school age children. Early fetal life might be a
      critical period for cardiovascular health in later life.

PMID- 24458587
TI  - Hydrops fetalis in a preterm newborn heterozygous for the c.4A>G SHOC2 mutation.
AB  - Fetal hydrops is a condition resulting from interstitial fluid accumulation in
      fetal compartments secondary to increased capillary permeability and
      characterized by high rates of perinatal mortality and morbidity. Clinical
      features include skin edema, hydrothorax, pericardial effusion, ascites with or
      without polyhydramnios, and placental edema. While it may occur as associated
      feature in multiple disorders, it has been documented to recur in Noonan
      syndrome, the most common disorder among RASopathies, but also in
      cardiofaciocutaneous and Costello syndromes. Here, we report on the occurrence of
      severe hydrops in a newborn heterozygous for the invariant c.4A>G missense change
      in SHOC2 which underlies Noonan-like syndrome with loose anagen hair, documenting
      that it represents a clinically relevant complication in this condition, shared
      by RASopathies.

PMID- 24458588
TI  - Computational and experimental investigation of local stress fiber orientation in
      uniaxially and biaxially constrained microtissues.
AB  - The orientation of cells and associated F-actin stress fibers is essential for
      proper tissue functioning. We have previously developed a computational model
      that qualitatively describes stress fiber orientation in response to a range of
      mechanical stimuli. In this paper, the aim is to quantitatively validate the
      model in a static, heterogeneous environment. The stress fiber orientation in
      uniaxially and biaxially constrained microscale tissues was investigated using a
      recently developed experimental system. Computed and experimental stress fiber
      orientations were compared, while accounting for changes in orientation with
      location in the tissue. This allowed for validation of the model, and
      additionally, it showed how sensitive the stress fiber orientation in the
      experimental system is to the location where it is measured, i.e., the
      heterogeneity of the stress fiber orientation. Computed and experimental stress
      fiber orientations showed good quantitative agreement in most regions. A strong
      local alignment near the locations where boundary conditions were enforced was
      observed for both uniaxially and biaxially constrained tissues. Excepting these
      regions, in biaxially constrained tissues, no preferred orientation was found and
      the distribution was independent of location. The stress fiber orientation in
      uniaxially constrained tissues was more heterogeneous, and stress fibers mainly
      oriented in the constrained direction or along the free edge. These results
      indicate that the stress fiber orientation in these constrained microtissues is
      mainly determined by the local mechanical environment, as hypothesized in our
      model, and also that the model is a valid tool to predict stress fiber
      orientation in heterogeneously loaded tissues. 

PMID- 24458589
TI  - Genetic structure of Bemisia tabaci Med populations from home-range countries,
      inferred by nuclear and cytoplasmic markers: impact on the distribution of the
      insecticide resistance genes.
AB  - BACKGROUND: Insecticide resistance management in Bemisia tabaci is one of the
      main issues facing agricultural production today. An extensive survey was
      undertaken in five Mediterranean countries to examine the resistance status of
      Med B. tabaci species in its range of geographic origin and the relationship
      between population genetic structure and the distribution of resistance genes.
      The investigation combined molecular diagnostic tests, sequence and
      microsatellite polymorphism studies and monitoring of endosymbionts. RESULTS:
      High frequencies of pyrethroid (L925I and T929V, VGSC gene) and organophosphate
      (F331W, ace1 gene) resistance mutations were found in France, Spain and Greece,
      but not in Morocco or Tunisia. Sequence analyses of the COI gene delineated two
      closely related mitochondrial groups (Q1 and Q2), which were found either
      sympatrically (Spain) or separately (France). Only Q1 was observed in Greece,
      Morocco and Tunisia. Bayesian analyses based on microsatellite loci revealed
      three geographically delineated genetic groups (France, Spain,
      Morocco/Greece/Tunisia) and high levels of genetic differentiation even between
      neighbouring samples. Evidence was also found for hybridisation and asymmetrical
      gene flow between Q1 and Q2. CONCLUSIONS: Med B. tabaci is more diverse and
      structured than reported so far. On a large geographic scale, resistance is
      affected by population genetic structure, whereas on a local scale, agricultural
      practices appear to play a major role.

PMID- 24458590
TI  - Dinuclear ruthenium(II) complexes as two-photon, time-resolved emission
      microscopy probes for cellular DNA.
AB  - The first transition-metal complex-based two-photon absorbing luminescence
      lifetime probes for cellular DNA are presented. This allows cell imaging of DNA
      free from endogenous fluorophores and potentially facilitates deep tissue
      imaging. In this initial study, ruthenium(II) luminophores are used as
      phosphorescent lifetime imaging microscopy (PLIM) probes for nuclear DNA in both
      live and fixed cells. The DNA-bound probes display characteristic emission
      lifetimes of more than 160 ns, while shorter-lived cytoplasmic emission is also
      observed. These timescales are orders of magnitude longer than conventional FLIM,
      leading to previously unattainable levels of sensitivity, and autofluorescence
      free imaging.

PMID- 24458591
TI  - cAMP-PKA inhibition of SK3 channel reduced both Ca2+ entry and cancer cell
      migration by regulation of SK3-Orai1 complex.
AB  - SK3 channel mediates the migration of various cancer cells. When expressed in
      breast cancer cells, SK3 channel forms a complex with Orai1, a voltage
      independent Ca(2+) channel. This SK3-Orai1 complex associates within lipid rafts
      where it controls a constitutive Ca(2+) entry leading to cancer cell migration
      and bone metastases development. Since cAMP was found to modulate breast cancer
      cell migration, we hypothesized that this could be explained by a modulation of
      SK3 channel activity. Herein, we study the regulation of SK3 channel by the cAMP
      PKA pathway and the consequences for SK3-dependent Ca(2+) entry and cancer cell
      migration. We established that the beta-adrenergic receptor agonist,
      isoprenaline, or the direct adenylyl cyclase activator forskolin alone or in
      combination with the PDE4 inhibitor, CI-1044, decreased SK3 channel activity
      without modifying the expression of SK3 protein at the plasma membrane. Forskolin
      and CI-1044 reduced the SK3-dependent constitutive Ca(2+) entry and the SK3
      dependent migration of MDA-MB-435s cells. PKA inhibition with KT 5720 reduced:
      (1) the effect of forskolin and CI-1044 by 50 % on Ca(2+) entry and (2) SK3
      activity by inhibiting the serine phosphorylation of SK3. These cAMP-elevating
      agents displaced Orai1 protein outside lipid rafts in contrast to SK3, which
      remained in the lipid rafts fractions. All together, these results show that
      activation of the cAMP-PKA pathway decreases SK3 channel and SK3-Orai1 complex
      activities, leading to a decrease in both Ca(2+) entry and cancer cell migration.
      This work supports the potential use of cAMP-elevating agents to reduce cancer
      cell migration and may provide novel opportunities to address/prevent bone
      metastasis. 

PMID- 24458592
TI  - Clinical and radiological outcome of the Total Evolutive Shoulder System
      (TESS(r)) reverse shoulder arthroplasty: a prospective comparative non-randomised
      study.
AB  - PURPOSE: The aims of this study were to assess the function and quality of life
      after the Total Evolutive Shoulder System (TESS) reverse shoulder arthroplasty
      (RSA), to evaluate the radiological stability of the stemless version and to
      address the effect of arm lengthening and scapular notching (SN) on the outcome.
      METHODS: This was a prospective comparative non-randomised study. A total of 37
      consecutive patients (40 shoulders) underwent TESS RSA between October 2007 and
      January 2012; 16 were stemless and 26 were stemmed. At a mean follow-up of 39
      months (15-66), we evaluated range of motion (ROM), pain and functional outcome
      with QuickDASH and quality of life with EQ-5D score. Radiologically, component
      positioning, signs of loosening, SN and arm length difference were documented.
      RESULTS: We found a significant improvement in functional outcome and reduction
      of pain in both stemmed and stemless groups. No humeral loosening was evident,
      but there were four glenoid loosenings. In 12 shoulders that developed SN, seven
      already had scapular bone impression (SBI) evident on initial post-operative
      radiographs. Glenoid overhang seemed to decrease the risk of SN. Arm lengthening
      was associated with better EQ-5D but did not influence ROM or functional outcome.
      CONCLUSIONS: Reverse shoulder arthroplasty markedly improved shoulder function.
      SN is of concern in RSA, but proper positioning of the glenoid component may
      prevent its development.

PMID- 24458593
TI  - New technology in anaesthesia: friend or foe?

PMID- 24458594
TI  - Listening to breathing again!

PMID- 24458595
TI  - Exploring the contribution of psychosocial factors to fatigue in patients with
      advanced incurable cancer.
AB  - OBJECTIVE: Fatigue is the most frequently occurring and distressing symptom in
      patients with advanced cancer, caused by multiple factors. Neither a specific
      histological diagnosis of malignancy nor the type of anticancer treatment seem to
      be strongly related to fatigue, which support the idea that other factors may
      play a role. This study investigated to what extent the model of fatigue
      perpetuating factors that is known for cancer survivors was applicable for
      patients with advanced cancer. METHODS: Patients on active treatment for various
      incurable cancers were asked to complete the Checklist Individual Strength,
      subscale fatigue severity and physical activity, the Acceptance scale of the
      Illness Cognition Questionnaire, the Hospital Anxiety and Depression Scale, the
      Fatigue Catastrophizing Scale, the Symptom Checklist subscale sleep, and the van
      Sonderen Social Support List-Discrepancies. RESULTS: The questionnaires were
      filled in by 137 patients. Inappropriate coping, fear of progression, fatigue
      catastrophizing, discrepancies in social support, depressive mood, self reported
      physical activity, and sleeping problems were all related to fatigue severity in
      univariate analyses, of which the latter two were significant in a multivariate
      linear regression analysis. CONCLUSION: This study tested fatigue-perpetuating
      factors known to be of relevance in cancer survivors, for their relation with
      fatigue severity in palliative patients. We demonstrated that these factors were
      also relevant for patients on palliative treatment. On the basis of our results,
      we suggest clinicians confronted with palliative patients with serious fatigue to
      address sleeping problems and promote physical activity. In case of persistent
      fatigue, personalized cognitive behavioral therapy can be considered.

PMID- 24458596
TI  - Coarctation of the aorta in Noonan-like syndrome with loose anagen hair.
AB  - Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) due to a
      missense mutation c.4A>G in SHOC2 predicting p.Ser2Gly has been described
      recently. This condition is characterized by facial features similar to Noonan
      syndrome, reduced growth, cardiac defects, and typical abnormal hair. We report
      on a patient with molecularly confirmed NS/LAH with coarctation of the aorta. The
      girl was precipitously born at 37 weeks of gestation at home and required a 3-min
      resuscitation. Increased nuchal translucency and aortic coarctation with a small
      ventricular septal defect were described prenatally, hypertrophic cardiomyopathy
      was detected postnatally. The patient presented with facial dysmorphism typical
      of NS with redundant skin over the nape and on the back. Short stature, relative
      macrocephaly, failure-to-thrive together with dystrophic appearance,
      developmental delay mainly in motor milestones and very thin, sparse, slow
      growing hair occurred a few weeks after birth. Endocrine evaluation revealed low
      IGF-1 levels and borderline growth hormone deficiency. Growth hormone therapy
      started at 16 months had a partial effect and prevented further growth
      deterioration. Coarctation of the aorta is not a typical heart defect among
      individuals with NS/LAH, therefore our observation extends the phenotypic
      spectrum of this disorder.

PMID- 24458597
TI  - alpha-Fe2O3 cubes with high visible-light-activated photoelectrochemical activity
      towards glucose: hydrothermal synthesis assisted by a hydrophobic ionic liquid.
AB  - A liquid/liquid interfacial reaction system was designed to fabricate alpha-Fe2O3
      cubes. The reaction system uses a hydrophobic ionic liquid containing iron ions
      ([(C8H17)2(CH3)2N]FeCl4) for manufacturing alpha-Fe2O3 cubes by a novel and
      environmentally friendly hydrothermal method under low-temperature conditions
      (140  degrees C). The iron-containing ionic liquid is hydrophobic and can form a
      liquid/liquid interface with water, which is vital for fabrication of the alpha
      Fe2O3 cubes. Nanomaterials synthesized from hydrophobic iron-containing ionic
      liquids show good crystallinity, well-developed morphology, and uniform size. The
      effect of different ionic liquids on the morphology of alpha-Fe2 O3 was
      investigated in detail. [(C8H17)2(CH3)2N]FeCl4 is assumed to perform the triple
      role of forming a liquid/liquid interface with water and acting as reactant and
      template at the same time. The effect of the reaction temperature on the
      formation of the alpha-Fe2O3 cubes was also studied. Temperatures lower or higher
      than 140  degrees C are not conducive to formation of the alpha-Fe2O3 cubes.
      Their photoelectrochemical properties were tested by means of the transient
      photocurrent response of electrodes modified with as-prepared alpha-Fe2O3 cubes.
      The photocurrent response of an alpha-Fe2O3 cubes/indium tin oxide electrode is
      high and stable, and it shows great promise as a photoelectrochemical glucose
      sensor with high sensitivity and fast response, which are beneficial to practical
      applications of nanosensors.

PMID- 24458598
TI  - Effects of light quality, CO2 tensions and NO 3 (+-) concentrations on the
      inorganic nitrogen metabolism of Chlamydomonas reinhardii.
AB  - The blue light dependent utilization of nitrate by green algae under common air
      and high irradiances, besides its assimilatory nature, is associated with the
      release of NO2 (-) and NH4 (+) to the culture medium. If the CO2 content of the
      sparging air was increased up to 2%, previously excreted NO2 (-) and NH4 (+) were
      rapidly assimilated. When under air and high irradiances the cell density in the
      culture reached values corresponding to 25 MUg Ch 1.ml(-1), no further growth was
      observed and the highest values of NO3 (-) consumption and NO2 (-) and NH4 (+)
      release were attained. Besides low CO2 tensions, increasing NO3 (-)
      concentrations in the medium stimulated the release of NO3 (-) and NH4 (+). Under
      CO2-free air the consumption of NO3 (-) and the release of NO2 (-) and NH4 (+) on
      a total N bases were almost stoichiometric and their rates saturated at much
      lower irradiances than under air. Under CO2-free air high rates of NO2 (-)
      release were only observed under the blue radiations that were effectively
      absorbed by photosynthetically active pigments, i.e. 460 nm, but not under 404
      and 630 nm radiations. However, the simultaneous illumination of the cells with
      404 and 630 nm monochromatic light showed a remarkable synergistic effect on NO2
      (-) release.The results are discussed in terms of the close relationship between
      C and N metabolism, the photosynthetic reducing power required to convert NO inf3
      (sup+/-) -N into R - NH2-N and the blue light activation of nitrate reductase. 

PMID- 24458599
TI  - Adaptation of the thylakoid membranes of pea chloroplasts to light intensities.
      I. Study on the distribution of chlorophyll-protein complexes.
AB  - The effect of light intensity (16 h white light and 8 h dark) during growth of
      pea plants at 20 degrees C on the chlorophyll composition and on the relative
      distribution of chlorophyll amongst the various chlorophyll-protein of pea
      thylakoids was studied. The chl a/chl b ratios increased from 2.1 to 3.2 as light
      intensity during growth varied from 10 to 840 MUEm(-2) s(-1). This function can
      be described by two straight lines intersecting at a transition point of
      approximately 200 MUEm(-2) s(-1). Similar discontinuities in the responses were
      observed in the changes in the relative distribution of chlorophyll amongst the
      various chlorophyll-protein complexes. This demonstrates that the chl a/chl b
      ratio of the various thylakoids is a good indicator of changes in the relative
      distribution of chlorophyll. As the chl a/chl b ratio decreased, the amount of
      chlorophyll associated with photosystem I complexes decreased, that with
      photosystem II core reaction centre complex was halved, and that with the main
      chl a/b-proteins of the light-harvesting complex was markedly increased. 

PMID- 24458600
TI  - Adaptation of the thylakoid membranes of pea chloroplasts to light intensities.
      II. Regulation of electron transport capacities, electron carriers, coupling
      factor (CF1) activity and rates of photosynthesis.
AB  - The electron transport rates of photosystems II and I, amounts of electron
      carriers, coupling factor activity and photosynthetic rates were investigated in
      thylakoids isolated from pea plants grown under a wide range of light intensities
      (16 h light-8 h dark). The electron transport rates of PS II and PS I, as partial
      reactions or in whole chain, and coupling factor activity on a unit chlorophyll
      basis, all increased as the light intensity available for growth was altered from
      a very low intensity of 10 MUE m(-2)s(-1) to a high intensity of 840 MUE m(-2)s(
      1). Similarly, there were increases in the amounts of atrazine binding sites,
      plastoquinine, cytochrome f and P700 per unit chlorophyll; significantly, the
      amounts of reaction centres of PS II and PS I were not equal at any light
      intensity. The rate of change of all parameters with respect to light intensity
      could be represented by two straight lines of different slopes which met at a
      transition point corresponding to approximately 200 MUE m(-2)s(-1) during growth.
      These photoadaptations were similar to those observed for both the relative
      distribution of chlorophyll in chlorophyll-protein complexes and the chl a/chl b
      ratios [Leong and Anderson, 1984, Photosynthesis Research 5:117-128]. Since these
      thylakoid components and functions were affected in the same direction by light
      intensity during growth and all show linear relationships with chl a/chl b
      ratios, it indicates that they are closely regulated and markedly well co
      ordinated. Plants compensate for the limited amount of low light intensities by
      drastically increasing the light-harvesting antenna unit size of photosystem II
      and to a lesser extent that of photosystem I. Changes in the composition of the
      thylakoid membranes exert a regulatory effect on the overall photosynthetic rate
      up to approximately 450 MUE m(-2)s(-1). 

PMID- 24458601
TI  - Use of 8-analino-1-naphthalene sulfonate as a monitor for possible phase
      transition involving water at low temperatures in photoreaction center from
      Rhodospirillum rubrum.
AB  - The increase in the rate of the primary back reaction on cooling the
      photoreaction center from Rhodospirillum rubrum was interpreted in terms of a
      model in which the peculiar temperature dependence of the rate results from a
      phase transition involving water. The primary back reaction is defined as the
      return of the electron from the reduced primary ubiquinone to the oxidized
      bacteriochlorophyll molecules following illumination. The dye 8-anilino-1
      naphthalene sulfonate was used to detect the state of the water solvent as it
      transforms on cooling from a liquid to a solid glass. We inferred from studies
      with air-dried films of photoreaction center that the water which may be
      responsible for the unusual temperature dependence of the rate of the primary
      back reaction is not on the surface but is bound within the photoreaction center
      protein. 

PMID- 24458602
TI  - Chlorophyll fluorescence as a tool in plant physiology : II. Interpretation of
      fluorescence signals.

PMID- 24458603
TI  - Partial characterization of a minor chlorophyll-protein found in primary
      thylakoids of intermittently illuminated maize.
AB  - A mild solubilization with sodium dodecyl sulphate of intermittently illuminated
      maize (Zea mays L. Mvsc 429) thylakoids allows the separation of a minor
      chlorophyll-protein in the position of the light harvesting chlorophyll-protein
      monomer of green plants by polyacrylamide gel electrophoresis. It contains mainly
      chlorophyll a, its chlorophyll b content may come from the slightly contaminating
      light harvesting chlorophyll a/b-protein. It represents about 15% of the
      chlorophyll in protochloroplasts. The new chlorophyll-protein has an absorption
      maximum at 672 nm, and only one fluorescence emission peak at 680 nm. A 34 kD
      polypeptide is the most abundant one in the polypeptide pattern of the complex.
      The function of the new chlorophyll-protein is unknown at present. Its
      relationship to other chlorophyll-proteins is discussed. 

PMID- 24458604
TI  - Influence of carbon dioxide concentration during growth on fluorescence induction
      characteristics of the Green Alga Chlamydomonas reinhardii.
AB  - Carbon dioxide concentration during growth is commonly not considered to be a
      factor influencing the photochemical properties of plants. It was observed that
      fluorescence induction in Chlamydomonas reinhardii cells grown at air levels of
      CO2 was both qualitatively and quantitatively different from that of cells grown
      at 5% CO2. In the two cell types, measured at equivalent chlorophyll and
      irradiance levels, the fluorescence intensity and the ratio of the levels of peak
      fluorescence (Fp) to that of the initial fluorescence (Fo) were much lower in the
      air-adapted than in the 5% CO2 adapted cells. The maximum fluorescence (Fmax) in
      the presence of diuron was also lower for air-adapted cells. Roughly twice the
      light input was required for the air-adapted cells to give a fluorescence
      induction transient and intensity equivalent to that of the 5% CO2-adapted cells.
      Similar properties were observed in several other unicellular green algae and in
      cyanobacteria. Chlamydomonas grown under variable CO2 concentrations exhibit
      significant differences in photosynthetic carbon metabolism and are presumed to
      have altered energy requirements. The observed variation in fluorescence
      induction may be due to changes in the properties of the thylakoid reactions
      (e.g. cyclic electron flow) of Chlamydomonas cells, which may, in turn, be due to
      a response to the altered energy requirements. 

PMID- 24458605
TI  - The action of lipases on chloroplast membranes. III. The effect of lipid
      hydrolysis on chlorophyll-protein complexes in thylakoid membranes.
AB  - Bean thylakoid membranes treated with various lipolytic enzymes (bean
      galactolipase, phospholipases A2, C, D) showed marked changes in their acyl lipid
      composition. As a consequence of acyl lipids hydrolysis, destruction of some
      chlorophyll a-protein complexes (CP1a, CP1, CPa) or monomerization of the
      oligomeric of light harvesting chlorophyll a/b protein complex (LHCP) was
      observed. It is concluded that galactolipids and phosphatidylcholine are
      responsible for the stability of CP1a, CP1 and CPa, respectively.
      Phosphatidylglycerol and to some extent monogalactosyldiacylglycerol are
      essential for the stabilization of oligomeric structures of light harvesting
      chlorophyll a/b protein complex. 

PMID- 24458606
TI  - Reactivation by chloride of hill activity in heat- and tris-treated thylakoid
      membranes from Beta vulgaris.
AB  - Hill activity (photoreduction of 2,6,dichlorophenol indophenol) of heat
      inactivated (40 degrees C, 3 min) and Tris-washed (0.8M, pH 8.3) thylakoids of
      Beta vulgaris (beet-spinach) was partially restored if they were incubated with
      150 mM MgCl2 prior to the assay. Mg(NO3)2 or MgSO4 were unable to restore this
      activity. The extent of this reactivation was dependent upon the degree of
      inactivation by heating and upon the composition of the isolation and the
      resuspension buffer used during the heat treatment. Washing of heat-treated
      thylakoids with phosphate-EDTA buffer prior to incubation with MgCl2 did not
      affect the extent of this reactivation. Chloride ions seem to be required for the
      reactivation of Hill activity damaged either by heat or by Tris.Most commonly
      used chloroplast isolation and resuspension media, except for Tris-HCl as
      resuspension medium, were suitable for restoration of Hill activity in heat
      damaged thylakoids by preincubation with 150 mM MgCl2 prior to the assay.
      Pretreatment with MgCl2 stimulated Hill activity in Tris-treated and heat-damage
      thylakoids if phosphate buffer was used for their resuspension. However, the same
      pretreatment inhibited Hill activity in unheated thylakoids isolated in Tris
      medium and resuspended in the same medium. On the other hand, MgCl2 pretreatment
      induced restoration of the Hill activity of the heated thylakoids when Tricine or
      Hepes was used as the resuspension medium. It appears that the presence of Tris
      somehow hampers the Cl(-) induced reactivation. The stimulation of Hill activity
      by MgCl2 treatment in unheated (control) thylakoids is possibly induced by Mg(2+)
      ions and not by Cl(-) ions. 

PMID- 24458607
TI  - Controlled pixelation of inverse opaline structures towards reflection-mode
      displays.
AB  - Pixelated inverse opals with red, green, and blue colors were prepared by
      hybridizing convective assembly of colloidal particles and photolithography
      techniques. The brilliant structural colors, high mechanical stability, and small
      feature size of the pixels were simultaneously accomplished, thereby providing
      color reflectors potentially useful for display devices. Moreover, this
      hybridized method provides a general means to create multi-colored photonic
      crystals. 

PMID- 24458608
TI  - Evaluation of ultrasound and glucose synergy effect on the optical clearing and
      light penetration for human colon tissue using SD-OCT.
AB  - Topical application optical clearing agents (OCAs) can effectively enhance the
      tissue optical clearing on the human colon tissue, which has been demonstrated in
      our previous studies. Nevertheless, the strong light scattering still limits the
      diffusion rate of OCAs and penetration depth of light into the tissue. In this
      study, in order to further increase the diffusion of the OCA of glucose into
      tissue, we employ a method to improve the glucose permeability and light
      penetration with ultrasound (sonophoretic delivery, SP) and glucose (G) synergy
      on human normal and cancerous colon tissues in vitro, which was measured and
      quantified with spectral-domain optical coherence tomography (SD-OCT) technology.
      To evaluate the effect of ultrasound mediation, the percentages of OCT signal
      enhancement (PSE) and 1/e light-penetration depth were calculated for G alone and
      ultrasound-G treatments. The PSE was calculated at approximately 313 MUm from the
      sample tissue surface. For normal and cancerous colon tissues the PSE were about
      91.1 +/- 10.6% and 65.3% +/- 12.3% with 30% G/SP, but for the 30% G alone
      treatment it was about 78.6 +/- 11.2% and 54.5% +/- 9.3%, respectively. The max
      value of 1/e light-penetration depth for normal colon tissue was 0.47 +/- 0.02 mm
      with 30% G alone and 0.60 +/- 0.05 mm (p < 0.05)with 30% G/SP synergy. However,
      for the cancerous colon tissue the max value was 0.45 +/- 0.01 mm and 0.57 +/-
      0.03 mm (p < 0.05), respectively. The obtained permeability coefficients showed a
      significant enhancement with ultrasound mediation. The mean permeability
      coefficients of 30% G/SP in normal and cancerous colon tissues were (6.3 +/-
      0.16) * 10(-6) cm/s and (12.1 +/- 0.34) * 10(-6) cm/s (p < 0.05), respectively.
      These preliminary experiments showed that ultrasound can effectively enhance the
      tissue optical clearing and glucose diffusion rate as well as increase the light
      penetration depth into biotissues.

PMID- 24458610
TI  - Challenges for new ERC president.

PMID- 24458615
TI  - Clinical research. Divulging DNA secrets of dead stirs debate.

PMID- 24458616
TI  - U.S. spending. NIH is losing its funding edge, 2014 budget suggests.

PMID- 24458617
TI  - Materials science. Nano-imaging feud sets online sites sizzling.

PMID- 24458618
TI  - Intellectual property. Historic patent on embryonic stem cells faces scrutiny.

PMID- 24458619
TI  - Scholar rescue. A lifeline for Syria's science exiles.

PMID- 24458620
TI  - The epigenetics heretic.

PMID- 24458621
TI  - Selling America's fossil record.

PMID- 24458622
TI  - Flu threat spurs culture change.

PMID- 24458623
TI  - Regulating dual-use research in Europe.

PMID- 24458624
TI  - Misleading results: translational challenges.

PMID- 24458625
TI  - Misleading results: don't blame the mice.

PMID- 24458627
TI  - Information access. Raw personal data: providing access.

PMID- 24458628
TI  - Molecular biology. mRNA, live and unmasked.

PMID- 24458629
TI  - Cancer. Hiding in plain view--an ancient dog in the modern world.

PMID- 24458630
TI  - Biochemistry. Making the H-cluster from scratch.

PMID- 24458631
TI  - Atmospheric science. Climate effects of aerosol-cloud interactions.

PMID- 24458632
TI  - Physiology. Extraordinary color vision.

PMID- 24458633
TI  - Physics. Lifting the fog of complexity.

PMID- 24458634
TI  - Immunology. The fiery side of HIV-induced T cell death.

PMID- 24458635
TI  - Exploring martian habitability. Habitability, taphonomy, and the search for
      organic carbon on Mars. Introduction.

PMID- 24458636
TI  - Strong ground motion prediction using virtual earthquakes.
AB  - Sedimentary basins increase the damaging effects of earthquakes by trapping and
      amplifying seismic waves. Simulations of seismic wave propagation in sedimentary
      basins capture this effect; however, there exists no method to validate these
      results for earthquakes that have not yet occurred. We present a new approach for
      ground motion prediction that uses the ambient seismic field. We apply our method
      to a suite of magnitude 7 scenario earthquakes on the southern San Andreas fault
      and compare our ground motion predictions with simulations. Both methods find
      strong amplification and coupling of source and structure effects, but they
      predict substantially different shaking patterns across the Los Angeles Basin.
      The virtual earthquake approach provides a new approach for predicting long
      period strong ground motion. 

PMID- 24458637
TI  - Increased dust deposition in the Pacific Southern Ocean during glacial periods.
AB  - Dust deposition in the Southern Ocean constitutes a critical modulator of past
      global climate variability, but how it has varied temporally and geographically
      is underdetermined. Here, we present data sets of glacial-interglacial dust
      supply cycles from the largest Southern Ocean sector, the polar South Pacific,
      indicating three times higher dust deposition during glacial periods than during
      interglacials for the past million years. Although the most likely dust source
      for the South Pacific is Australia and New Zealand, the glacial-interglacial
      pattern and timing of lithogenic sediment deposition is similar to dust records
      from Antarctica and the South Atlantic dominated by Patagonian sources. These
      similarities imply large-scale common climate forcings, such as latitudinal
      shifts of the southern westerlies and regionally enhanced glaciogenic dust
      mobilization in New Zealand and Patagonia. 

PMID- 24458639
TI  - A different form of color vision in mantis shrimp.
AB  - One of the most complex eyes in the animal kingdom can be found in species of
      stomatopod crustaceans (mantis shrimp), some of which have 12 different
      photoreceptor types, each sampling a narrow set of wavelengths ranging from deep
      ultraviolet to far red (300 to 720 nanometers). Functionally, this chromatic
      complexity has presented a mystery. Why use 12 color channels when three or four
      are sufficient for fine color discrimination? Behavioral wavelength
      discrimination tests (Deltalambda functions) in stomatopods revealed a
      surprisingly poor performance, ruling out color vision that makes use of the
      conventional color-opponent coding system. Instead, our experiments suggest that
      stomatopods use a previously unknown color vision system based on temporal
      signaling combined with scanning eye movements, enabling a type of color
      recognition rather than discrimination.

PMID- 24458638
TI  - A peptide hormone and its receptor protein kinase regulate plant cell expansion.
AB  - Plant cells are immobile; thus, plant growth and development depend on cell
      expansion rather than cell migration. The molecular mechanism by which the plasma
      membrane initiates changes in the cell expansion rate remains elusive. We found
      that a secreted peptide, RALF (rapid alkalinization factor), suppresses cell
      elongation of the primary root by activating the cell surface receptor FERONIA in
      Arabidopsis thaliana. A direct peptide-receptor interaction is supported by
      specific binding of RALF to FERONIA and reduced binding and insensitivity to RALF
      induced growth inhibition in feronia mutants. Phosphoproteome measurements
      demonstrate that the RALF-FERONIA interaction causes phosphorylation of plasma
      membrane H(+)-adenosine triphosphatase 2 at Ser(899), mediating the inhibition of
      proton transport. The results reveal a molecular mechanism for RALF-induced
      extracellular alkalinization and a signaling pathway that regulates cell
      expansion. 

PMID- 24458640
TI  - Risky ripples allow bats and frogs to eavesdrop on a multisensory sexual display.
AB  - Animal displays are often perceived by intended and unintended receivers in more
      than one sensory system. In addition, cues that are an incidental consequence of
      signal production can also be perceived by different receivers, even when the
      receivers use different sensory systems to perceive them. Here we show that the
      vocal responses of male tungara frogs (Physalaemus pustulosus) increase twofold
      when call-induced water ripples are added to the acoustic component of a rival's
      call. Hunting bats (Trachops cirrhosus) can echolocate this signal by-product and
      prefer to attack model frogs when ripples are added to the acoustic component of
      the call. This study illustrates how the perception of a signal by-product by
      intended and unintended receivers through different sensory systems generates
      both costs and benefits for the signaler. 

PMID- 24458641
TI  - Endothelial cell-derived angiopoietin-2 controls liver regeneration as a
      spatiotemporal rheostat.
AB  - Liver regeneration requires spatially and temporally precisely coordinated
      proliferation of the two major hepatic cell populations, hepatocytes and liver
      sinusoidal endothelial cells (LSECs), to reconstitute liver structure and
      function. The underlying mechanisms of this complex molecular cross-talk remain
      elusive. Here, we show that the expression of Angiopoietin-2 (Ang2) in LSECs is
      dynamically regulated after partial hepatectomy. During the early inductive phase
      of liver regeneration, Ang2 down-regulation leads to reduced LSEC transforming
      growth factor-beta1 production, enabling hepatocyte proliferation by releasing an
      angiocrine proliferative brake. During the later angiogenic phase of liver
      regeneration, recovery of endothelial Ang2 expression enables regenerative
      angiogenesis by controlling LSEC vascular endothelial growth factor receptor 2
      expression. The data establish LSECs as a dynamic rheostat of liver regeneration,
      spatiotemporally orchestrating hepatocyte and LSEC proliferation through
      angiocrine- and autocrine-acting Ang2, respectively. 

PMID- 24458642
TI  - Single beta-actin mRNA detection in neurons reveals a mechanism for regulating
      its translatability.
AB  - The physical manifestation of learning and memory formation in the brain can be
      expressed by strengthening or weakening of synaptic connections through
      morphological changes. Local actin remodeling underlies some forms of plasticity
      and may be facilitated by local beta-actin synthesis, but dynamic information is
      lacking. In this work, we use single-molecule in situ hybridization to
      demonstrate that dendritic beta-actin messenger RNA (mRNA) and ribosomes are in a
      masked, neuron-specific form. Chemically induced long-term potentiation prompts
      transient mRNA unmasking, which depends on factors active during synaptic
      activity. Ribosomes and single beta-actin mRNA motility increase after
      stimulation, indicative of release from complexes. Hence, the single-molecule
      assays we developed allow for the quantification of activity-induced unmasking
      and availability for active translation. Further, our work demonstrates that beta
      actin mRNA and ribosomes are in a masked state that is alleviated by stimulation.

PMID- 24458643
TI  - Visualization of dynamics of single endogenous mRNA labeled in live mouse.
AB  - The transcription and transport of messenger RNA (mRNA) are critical steps in
      regulating the spatial and temporal components of gene expression, but it has not
      been possible to observe the dynamics of endogenous mRNA in primary mammalian
      tissues. We have developed a transgenic mouse in which all beta-actin mRNA is
      fluorescently labeled. We found that beta-actin mRNA in primary fibroblasts
      localizes predominantly by diffusion and trapping as single mRNAs. In cultured
      neurons and acute brain slices, we found that multiple beta-actin mRNAs can
      assemble together, travel by active transport, and disassemble upon
      depolarization by potassium chloride. Imaging of brain slices revealed immediate
      early induction of beta-actin transcription after depolarization. Studying
      endogenous mRNA in live mouse tissues provides insight into its dynamic
      regulation within the context of the cellular and tissue microenvironment. 

PMID- 24458644
TI  - The HydG enzyme generates an Fe(CO)2(CN) synthon in assembly of the FeFe
      hydrogenase H-cluster.
AB  - Three iron-sulfur proteins--HydE, HydF, and HydG--play a key role in the
      synthesis of the [2Fe](H) component of the catalytic H-cluster of FeFe
      hydrogenase. The radical S-adenosyl-L-methionine enzyme HydG lyses free tyrosine
      to produce p-cresol and the CO and CN(-) ligands of the [2Fe](H) cluster. Here,
      we applied stopped-flow Fourier transform infrared and electron-nuclear double
      resonance spectroscopies to probe the formation of HydG-bound Fe-containing
      species bearing CO and CN(-) ligands with spectroscopic signatures that evolve on
      the 1- to 1000-second time scale. Through study of the (13)C, (15)N, and (57)Fe
      isotopologs of these intermediates and products, we identify the final HydG-bound
      species as an organometallic Fe(CO)2(CN) synthon that is ultimately transferred
      to apohydrogenase to form the [2Fe](H) component of the H-cluster.

PMID- 24458645
TI  - Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2
      barrier immunity.
AB  - How the immune system adapts to malnutrition to sustain immunity at barrier
      surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of
      the most common micronutrient deficiencies and is associated with profound
      defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells
      (ILC3s) are severely diminished in vitamin A-deficient settings, which results in
      compromised immunity to acute bacterial infection. However, vitamin A deprivation
      paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing
      ILC2s and resistance to nematode infection in mice, which revealed that ILCs are
      primary sensors of dietary stress. Further, these data indicate that, during
      malnutrition, a switch to innate type 2 immunity may represent a powerful
      adaptation of the immune system to promote host survival in the face of ongoing
      barrier challenges. 

PMID- 24458647
TI  - A paleogenomic perspective on evolution and gene function: new insights from
      ancient DNA.
AB  - The publication of partial and complete paleogenomes within the last few years
      has reinvigorated research in ancient DNA. No longer limited to short fragments
      of mitochondrial DNA, inference of evolutionary processes through time can now be
      investigated from genome-wide data sampled as far back as 700,000 years.
      Tremendous insights have been made, in particular regarding the hominin lineage.
      With rare exception, however, a paleogenomic perspective has been mired by the
      quality and quantity of recoverable DNA. Though conceptually simple, extracting
      ancient DNA remains challenging, and sequencing ancient genomes to high coverage
      remains prohibitively expensive for most laboratories. Still, with improvements
      in DNA isolation and declining sequencing costs, the taxonomic and geographic
      purview of paleogenomics is expanding at a rapid pace. With improved capacity to
      screen large numbers of samples for those with high proportions of endogenous
      ancient DNA, paleogenomics is poised to become a key technology to better
      understand recent evolutionary events. 

PMID- 24458646
TI  - Transmissible [corrected] dog cancer genome reveals the origin and history of an
      ancient cell lineage.
AB  - Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell
      lineage. It is a transmissible cancer that propagates naturally in dogs. We
      sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9
      million somatic substitution mutations and bears evidence of exposure to
      ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity
      despite thousands of rearrangements, copy-number changes, and retrotransposon
      insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes
      have been lost. CTVT first arose in a dog with low genomic heterozygosity that
      may have lived about 11,000 years ago. The cancer spawned by this individual
      dispersed across continents about 500 years ago. Our results provide a genetic
      identikit of an ancient dog and demonstrate the robustness of mammalian somatic
      cells to survive for millennia despite a massive mutation burden. 

PMID- 24458648
TI  - Ancient aqueous environments at Endeavour crater, Mars.
AB  - Opportunity has investigated in detail rocks on the rim of the Noachian age
      Endeavour crater, where orbital spectral reflectance signatures indicate the
      presence of Fe(+3)-rich smectites. The signatures are associated with fine
      grained, layered rocks containing spherules of diagenetic or impact origin. The
      layered rocks are overlain by breccias, and both units are cut by calcium sulfate
      veins precipitated from fluids that circulated after the Endeavour impact.
      Compositional data for fractures in the layered rocks suggest formation of Al
      rich smectites by aqueous leaching. Evidence is thus preserved for water-rock
      interactions before and after the impact, with aqueous environments of slightly
      acidic to circum-neutral pH that would have been more favorable for prebiotic
      chemistry and microorganisms than those recorded by younger sulfate-rich rocks at
      Meridiani Planum. 

PMID- 24458649
TI  - Non-clinical health services--what do they contribute to patient care and how can
      we measure their contribution?
AB  - BACKGROUND AND AIMS: Assessing the contribution of 'support services' to
      improving healthcare is challenging. Despite involving a significant part of the
      NHS budget, there is very little published literature on methods and approaches.
      This article describes the development of an integrated approach to assessing and
      measuring the health impact of these services. METHODS AND RESULTS: An empirical
      approach was developed by the main provider of national support services to NHS
      Scotland. This involved identifying meaningful ways to describe health impact of
      services several steps removed from patient care, applying this to the full range
      of national support services provided by NHS National Services Scotland and
      developing relevant measurement methodologies. Through this approach it was
      possible to assess the relative health impact of all 63 NSS services and to use
      this for planning and prioritisation. CONCLUSION: Assessing the contribution of
      support services to improving patient outcomes is a neglected area, despite the
      significant dependency of direct patient care services upon these services and
      the resource involved. The methods described in this article have potential to be
      used across the range of support services within the NHS to improve quality and
      efficiency of healthcare services.

PMID- 24458651
TI  - An in vitro study of lipid preference in whaleworm (Anisakis simplex, Nematoda,
      Ascaridoidea, Anisakidae) third-stage larvae.
AB  - The behavioural response of nematodes to chemical stimuli has been extensively
      investigated in some free-living and plant parasitic species. However, in animal
      parasitic species, little is yet known, particularly in regards to marine forms
      such as the whaleworm (Anisakis simplex). Previous studies showed that A. simplex
      L3-larvae tend to prefer fish tissue with high lipid content. The intention of
      this study was to investigate the behaviour of A. simplex L3 in response to
      different concentrations of fish lipid in further detail. This was done by an in
      vitro study based on larvae from cod (Gadus morhua). Ten larvae were placed in
      each of the culture containers containing agar that was separated into three
      segments of equal size. Three categories of agar were used containing 0, 2 and 7%
      cod liver oil. A total of 900 larvae were included. The study consisted of three
      parts: The purpose of experiment I was to establish whether different lipid
      concentrations influenced the migration pattern at all. Experiment II was
      intended to examine whether A. simplex L3-larvae were able to actively search for
      lipids. Experiment III was set up to analyse the short-distance dispersion of the
      L3-larvae. Experiment I indicated that the L3-larvae move randomly but do not
      stop randomly since the tendency to move out of the start area was inversely
      correlated with lipid concentration. Experiment II indicates that the larvae are
      almost unable to select areas of high lipid concentrations when more than a few
      centimetres away. Experiment III showed that the L3-larvae prefer high-fat
      content and can seek it out over short distances.

PMID- 24458650
TI  - Insulin therapy in children and adolescents with type 1 diabetes.
AB  - Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of
      exogenous insulin. The primary goal of treatment of T1DM in children and
      adolescents is to maintain near-normoglycemia through intensive insulin therapy,
      avoid acute complications, and prevent long-term microvascular and macrovascular
      complications, while facilitating as close to a normal life as possible.
      Effective insulin therapy must, therefore, be provided on the basis of the needs,
      preferences, and resources of the individual and the family for optimal
      management of T1DM. To achieve target glycemic control, the best therapeutic
      option for patients with T1DM is basal-bolus therapy either with multiple daily
      injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many
      formulations of insulin are available to help simulate endogenous insulin
      secretion as closely as possible in an effort to eliminate the symptoms and
      complications of hyperglycemia, while minimizing the risk of hypoglycemia
      secondary to therapy. When using MDI, basal insulin requirements are given as an
      injection of long- or intermediate-acting insulin analogs, while meal-related
      glucose excursions are controlled with bolus injections of rapid-acting insulin
      analogs. Alternatively, CSII can be used, which provides a 24-h preselected but
      adjustable basal rate of rapid-acting insulin, along with patient-activated
      mealtime bolus doses, eliminating the need for periodic injections. Both MDI
      treatment and CSII therapy must be supported by comprehensive education that is
      appropriate for the individual needs of the patient and family before and after
      initiation. Current therapies still do not match the endogenous insulin profile
      of pancreatic beta-cells, and all still pose risks of suboptimal control,
      hypoglycemia, and ketosis in children and adolescents. The safety and success of
      a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood
      glucose and/or a continuous glucose monitoring system to avoid critical
      hypoglycemia and glucose variability. Regardless of the mode of insulin therapy,
      doses should be adapted on the basis of the daily pattern of blood glucose,
      through regular review and reassessment, and patient factors such as exercise and
      pubertal status. New therapy options such as sensor-augmented insulin pump
      therapy, which integrates CSII with a continuous glucose sensor, along with
      emerging therapies such as the artificial pancreas, will likely continue to
      improve safe insulin therapy in the near future. 

PMID- 24458652
TI  - Serologic survey for exposure following fatal Balamuthia mandrillaris infection.
AB  - Granulomatous amebic encephalitis (GAE) from Balamuthia mandrillaris, a free
      living ameba, has a case fatality rate exceeding 90% among recognized cases in
      the USA. In August 2010, a GAE cluster occurred following transplantation of
      infected organs from a previously healthy landscaper in Tucson, AZ, USA, who died
      from a suspected stroke. As B. mandrillaris is thought to be transmitted through
      soil, a serologic survey of landscapers and a comparison group of blood donors in
      southern Arizona was performed. Three (3.6%) of 83 serum samples from landscapers
      and 11 (2.5%) of 441 serum samples from blood donors were seropositive (p =
      0.47). On multivariable analysis, county of residence was associated with
      seropositivity, whereas age, sex, and ethnicity were not. Exposure to B.
      mandrillaris, previously unexamined in North America, appears to be far more
      common than GAE in Southern Arizona. Risk factors for disease progression and the
      ameba's geographic range should be examined.

PMID- 24458653
TI  - RNAi-mediated silencing of enolase confirms its biological importance in
      Clonorchis sinensis.
AB  - Clonorchis sinensis (C. sinensis) infection is still a common public health
      problem in freshwater fish consumption areas in Asian countries. More molecular
      evidence are required to speed up the prevention strategies to control this kind
      of infectious disease. In the present study, to confirm the biological importance
      of Csenolase followed by our previous observations of the key metabolic enzyme,
      we explored the RNA silence effect of the Csenolase-derived RNA interference
      (RNAi) in C. sinensis. The extramembranous region aa105-226 was selected as the
      target sequence of RNA silence. Csenolase-derived double strand RNA (dsRNA
      Csenolase, 366 bp) was synthetized and delivered into C. sinensis by soaking
      approach. The penetration of dsRNA into adult worms and metacercariae was tracked
      using fluorescently labeled RNA. Western blotting and qRT-PCR experiments were
      performed to determine dsRNA-Csenolase-silencing effect. Our results showed that,
      after incubating for 120 h, dsRNA-Csenolase could effectively target and
      downregulate the expression of Csenolase in both adult worms (P < 0.001) and
      metacercariae (P < 0.01), resulting in a remarkable killing effect on C. sinensis
      adult worms (P < 0.01). Fluorescent Cy3-labeled dsRNA was mostly deposited in the
      uterus and vitellarium of adult worm and in the cyst wall of metacercaria. The
      present study is the first report of RNAi trials in C. sinensis, allowing further
      applications in identifying functional genes in C. sinensis.

PMID- 24458654
TI  - Undetermined impact of patient decision support interventions on healthcare costs
      and savings: systematic review.
AB  - OBJECTIVE: To perform a systematic review of studies that assessed the potential
      of patient decision support interventions (decision aids) to generate savings.
      DESIGN: Systematic review. DATA SOURCES: After registration with PROSPERO, we
      searched 12 databases, from inception to 15 March 2013, using relevant MeSH terms
      and text words. Included studies were assessed with Cochrane's risk of bias
      method and Drummond's quality checklist for economic studies. Per patient costs
      and projected savings associated with introducing patient decision support
      interventions were calculated, as well as absolute changes in treatment rates
      after implementation. ELIGIBILITY CRITERIA: Studies were included if they
      contained quantitative economic data, including savings, spending, costs, cost
      effectiveness analysis, cost benefit analysis, or resource utilization. We
      excluded studies that lacked quantitative data on savings, costs, monetary value,
      and/or resource utilization. RESULTS: After reviewing 1508 citations, we included
      seven studies with eight analyses. Of these seven studies, four analyses
      predicted system-wide savings, with two analyses from the same study. The
      predicted savings range from $8 (L5, ?6) to $3068 (L1868, ?2243) per patient.
      Larger savings accompanied reductions in treatment utilization rates. The impact
      on utilization rates was mixed. Authors used heterogeneous methods to allocate
      costs and calculate savings. Quality scores were low to moderate (median 4.5,
      range 0-8 out of 10), and risk of bias across the studies was moderate to high
      (3.5, range 3-6 out of 6), with studies predicting the most savings having the
      highest risk of bias. The range of issues identified in the studies included the
      relative absence of sensitivity analyses, the absence of incremental cost
      effectiveness ratios, and short time periods. CONCLUSION: Although there is
      evidence to show that patients choose more conservative approaches when they
      become better informed, there is insufficient evidence, as yet, to be confident
      that the implementation of patient decision support interventions leads to system
      wide savings. Further work-with sensitivity analyses, longer time horizons, and
      more contexts-is required to avoid premature or unrealistic expectations that
      could jeopardize implementation and lead to the loss of already proved benefits.
      REGISTRATION: PROSPERO registration CRD42012003421.

PMID- 24458655
TI  - Construction of a laccase chimerical gene: recombinant protein characterization
      and gene expression via yeast surface display.
AB  - The ERY4 laccase gene from Pleurotus eryngii was expressed in Saccharomyces
      cerevisiae and the recombinant laccase resulted to be not biologically active.
      This gene was thus modified to obtain chimerical enzymes derived from the
      substitution of N-, C- and both N- and C-terminal regions with the corresponding
      regions of Ery3 laccase, another laccase isoform of P. eryngii. The chimerical
      isoform named 4NC3, derived from the substitution of both N- and C-terminal
      regions, showed the best performances in terms of enzymatic activities,
      affinities for different substrates and stability at a broad range of
      temperatures and pHs. The chimerical 4NC3 laccase isoform was displayed on the
      cell surface of S. cerevisiae using the N-terminal fusion with either the Pir2 or
      the Flo1 S. cerevisiae proteins as anchor attachment sequence. Immunofluorescence
      microscopy and Western blot analyses confirmed the localization of 4NC3 on the
      yeast cell surface. The enzyme activity on specific laccase substrates revealed
      that 4NC3 laccase was immobilized in active form on the cell surface. To our
      knowledge, this is the first example of expression of a chimerical fungal laccase
      by yeast cell display. 

PMID- 24458656
TI  - Bioremediation of Cd by microbially induced calcite precipitation.
AB  - Contamination by Cd is a significant environmental problem. Therefore, we
      examined Cd removal from an environmental perspective. Ureolysis-driven calcium
      carbonate precipitation has been proposed for use in geotechnical engineering for
      soil remediation applications. In this study, 55 calcite-forming bacterial
      strains were newly isolated from various environments. Biomineralization of Cd by
      calcite-forming bacteria was investigated in laboratory-scale experiments. A
      simple method was developed to determine the effectiveness of microbially induced
      calcite precipitation (MICP). Using this method, we determined the effectiveness
      of biomineralization for retarding the flow of crystal violet through a 25-mL
      column. When the selected bacteria were analyzed using an inductively coupled
      plasma optical emission spectrometer, high removal rates (99.95%) of Cd were
      observed following incubation for 48 h. Samples of solids that formed in the
      reaction vessels were examined using a scanning electron microscope. The CdCO3
      compounds primarily showed a spherical shape. The results of this study
      demonstrate that MICP-based sequestration of soluble heavy metals via
      coprecipitation with calcite may be useful for toxic heavy metal bioremediation.

PMID- 24458657
TI  - A de novo 1.4-Mb deletion at 21q22.11 in a boy with developmental delay.
AB  - Monosomy 21 is a very rare chromosomal abnormality. At least 45 patients with
      partial deletion involving 21q11 have been reported. Here, we report a Japanese
      boy who presented with pre- and postnatal growth delays, psychomotor
      developmental delay, microcephaly, and iris coloboma. Cytogenetic analysis
      revealed a de novo 1.4-Mb deletion at 21q22.11 containing 19 protein-coding
      RefSeq genes. We compared the clinical phenotypes between the present patient and
      16 previously reported patients with a deleted region associated with postnatal
      growth delay and psychomotor developmental delay. Interestingly, ITSN1 was the
      only gene deleted or disrupted in all cases; this gene is known to be associated
      with intellectual disability. Microcephaly and brain structural abnormalities
      including polymicrogyria and agenesis/hypoplasia of the corpus callosum may also
      result from haploinsufficiency of ITSN1, highlighting its clinical significance
      for the neurological features of patients with monosomy 21.

PMID- 24458658
TI  - Building capacity for protected area management in Lao PDR.
AB  - Declining biodiversity in protected areas in Laos is attributed to unsustainable
      exploitation of natural resources. At a basic level, an important need is to
      develop capacity in academic and professional training institutions to provide
      relevant training to conservation professionals. The paper (a) describes the
      capacity building approach undertaken to achieve this goal, (b) evaluates the
      effectiveness of the approach in building capacity for implementing conservation
      and (c) reviews implementation outcomes. Strong linkages between organizations
      implementing field conservation, professional training institutions, and relevant
      Government agencies are central to enhancing effectiveness of capacity building
      initiatives aimed at improving the practice of conservation. Protected area
      management technical capacity needs will need to directly influence curriculum
      design to insure both relevance and effectiveness of training in improving
      protected area management. Sustainability of capacity building initiatives is
      largely dependent on the level of interest and commitment by host-country
      institutions within a supportive Government policy framework in addition to
      engagement of organizations implementing conservation. 

PMID- 24458659
TI  - Hypermedicalization in White Noise.
AB  - The Nazis hijacked Germany's medical establishment and appropriated medical
      language to hegemonize their ideology. In White Noise, shifting medical
      information stifles the public into docility. In Nazi Germany the primacy of
      language and medical authority magnified the importance of academic doctors. The
      muddling of identities caused complex insecurities and the need for psychological
      doubles. In White Noise, Professor Gladney is driven by professional insecurities
      to enact a double in Murray. Through the manipulation of language and medical
      overreach the U.S., exemplified in the novel White Noise, has become a
      hypermedicalized society where the spirit of the Hippocratic Oath has eroded. 

PMID- 24458660
TI  - Relationships between structural development and the absorption of ions by the
      root system of Cucurbita pepo.
AB  - In both the seminal axis and lateral roots of Cucurbita pepo L. the formation of
      large central xylem elements and the commencement of secondary cambial activity
      occur 10-20 cm from the root tip. Concomitant with or slightly preceding these
      developments there are changes in the structure of the walls of endodermal cells
      where the lignified casparian band spreads along the radial wall and substances
      staining with Sudan IV are deposited in both radial and tangential walls. At
      distances more than 30 cm from the tip of primary roots the radius of the stele
      increases considerably causing splits in the cortex. The endodermis is stretched
      and the suberin becomes organized in a lamellar form.Against this background of
      anatomical change certain of the transport capabilities of the root are retained
      while others are lost. Using an apparatus for measuring the uptake of tracers by
      segments of intact roots it was found that neither the uptake nor translocation
      of potassium seem to be affected by the suberization of the endodermis or by
      secondary thickening, while the translocation of calcium is virtually eliminated
      when these processes begin. As the root ages its ability to absorb phosphate
      declines although the translocation of the phosphate absorbed is much less
      affected by structural development than that of calcium.The observed rates of
      potassium uptake by complete root systems could be predicted quite accurately
      from the average of segment uptake data suggesting that the method used gives
      reliable results. 

PMID- 24458661
TI  - Initial proliferation of cortical cells in the formation of root nodules in Pisum
      sativum L.
AB  - Root nodule initiation in Pisum sativum begins with cell divisions in the inner
      cortex at some distance from the advancing infection thread. After penetrating
      almost the entire cortex, the branches of the thread infiltrate the meristematic
      area previously initiated in the inner cortical cells. These cells are soon
      invaded by bacteria released from the infection thread and subsequently
      differentiate into non-dividing, bacteriod-containing cells. As the initial
      meristematic centre in the inner cortex is thus lost to bacteroid formation, new
      meristematic activity is initiated in neighbouring cortical cells. As development
      proceeds, more cortical layers contribute to the nodule, with the peripheral
      layer and apical meristem of the nodule not invaded by bacteria.Lateral root
      primordia are initiated in a region separate from that in which nodules are
      formed, with the lateral primordia being closer to the root apex. This is
      interpreted to indicate that the physiological basis for nodule initiation is
      distinct from that for initiation of lateral roots. The role of a single
      tetraploid cell in nodule initiation is refuted, as is the existence of incipient
      meristematic foci in the root. It is suggested that the tetraploid cells in
      nodule meristems arise from pre-existing endoreduplicated cells, or by the
      induction of endoreduplication in diploid cortical cells by Rhizobium. 

PMID- 24458662
TI  - The role of hormones and gradients in the initiation of cortex proliferation and
      nodule formation in Pisum sativum L.
AB  - The effect of exogenous phytohormones on proliferation of the root cortex, and
      their relation to the division factors from Rhizobium which participate in the
      initiation of root nodules, were studied using explants of root-cortex tissue
      from 7-day-old, sterile pea plants. The explants were cultured for 7 days on a
      synthetic nutrient medium supplemented with auxin, or auxin and cytokinin. With
      only auxin present in the medium, ca. 10% of the explants showed cell
      proliferation. With both auxin and cytokinin this percentage was much higher (ca.
      80%). The active explants showed proliferation patterns which were similar to or
      could be derived from a pattern with three predominant meristematic areas in the
      inner cortex opposite the three xylem radii of the excised central cylinder.
      These proliferation patterns were similar to the initial proliferative stages in
      root-nodule formation in seedling intact roots. From this restricted division
      response of the explants to the hormones, a hypothesis of endogenous division
      factors is proposed. To test this hypothesis, extractions of root tissue were
      performed. The addition of a crude alcoholic extract from the central cylinder or
      the cortex to the medium resulted in cell divisions throughout the cortex. The
      results are interpreted as evidence for the presence of a transverse gradient
      system of (an) unknown cell-division factor(s) in the root cortex which may
      control the induction of cell divisions in nodule initiation brought about by the
      release of auxin and cytokinin from Rhizobium. 

PMID- 24458663
TI  - [Studies on the phloem exudate of Cucurbita pepo L. : I. Enzyme activities of
      aerobic and anaerobic glycolysis and of the citric acid cycle].
AB  - In the phloem exudate of Cucurbita pepo enzyme activities of aerobic and
      anaerobic glycolysis as well as of citric acid cycle were tested. All enzymes of
      the aerobic glycolysis and the alcoholic fermentation were present. In the phloem
      these metabolic pathways should be functioning as well. Since the lactate
      dehydrogenase could not be detected all the time, lactate fermentation is
      probably not an obligatory constituent of phloem metabolism. Of the citric acid
      cycle the enzymes malate dehydrogenase, isocitrate dehydrogenase, aconitase,
      fumarase and succinate dehydrogenase were analyzed. The activities decrease in
      the given order of enzymes. Succinate dehydrogenase could not be detected at all.
      The possibility of finding the citric acid cycle respectively mitochondria in the
      exudate is discussed. The results do not suggest the presence of such a metabolic
      pathway in the exudate. 

PMID- 24458664
TI  - [Studies on the phloem exudate of Cucurbita pepo L. : II. Enzyme activities of
      gluconeogenesis and of the synthesis and degradation of di- and polysaccharides].
AB  - Tests for enzymes of gluconeogenesis and of the synthesis and degradation of
      sucrose and polysaccharides have been carried out in the phloem exudate of
      Cucurbita pepo. All the enzymes which are necessary for the synthesis of sucrose
      and polysaccharides from metabolites of the citric acid cycle were found to be
      present in the exudate, except phosphoenolpyruvate carboxykinase. The
      polysaccharide synthetase was found to exhibit higher activity with glycogen
      (which is an unnatural polysaccharide in higher plants) than with starch. In
      addition, polysaccharide synthetase activity could be increased remarkably with 2
      mM glucose-6-phosphate and glycogen as primer. Among the enzymes which catabolize
      sucrose and polysaccharides (phosphorylase, invertase, sucrose phosphorylase),
      only sucrose phosphorylase showed activity. 

PMID- 24458665
TI  - Auxin-induced hydrogen-ion secretion in Avena coleoptiles and its implications.
AB  - The dose response curve for hydrogen-ion-induced extension growth in Avena
      coleoptile segments has been reinvestigated. The previously published optimum (pH
      3.0) is in error by about two orders of magnitude. The correct optimum is around
      pH 5.0. This discrepancy is thought to be due to the impermeable nature of the
      cuticle to hydrogen ions. In the present study the cuticular barrier to H(+)
      entry was circumvented by using coleoptile segments from which the epidermis with
      cuticle were physically removed. Using such peeled coleoptile sections, it was
      also found that auxin can rapidly (20-30 min) initiate H(+) secretion and that
      the magnitude of auxin-induced secretion is sufficient to initiate considerable
      cell-extension growth. Furthermore, it is shown that the secretion response is
      specific for active auxins, and inhibited by agents which inhibit auxin-induced
      growth (dinitrophenol, abscisic acid, cycloheximide, valinomycin and others).
      These results make it very likely that H(+) secretion is responsible, at least in
      part, for the initiation of auxin-induced cell wall loosening and extension
      growth. 

PMID- 24458666
TI  - [CO2-fixation metabolism in the halophytic species Mesembryanthemum crystallinum
      grown under different environmental conditions].
AB  - The correlation of CO2-fixation metabolism to various environmental conditions
      such as NaCl content of culture medium, air humidity and light intensity was
      investigated in the halophytic species Mesembryanthemum crystallinum. The data
      obtained demonstrate that a change in photosynthesis from C3-pathway to
      crassulacean acid metabolism (CAM) is observed not only in NaCl treated plants as
      reported earlier but also in control plants grown in non-saline medium when
      environmental conditions (high light intensity, low air humidity) cause a water
      deficit in the leaves. It is suggested that water stress plays an important role
      in regulation between C3- and CAM-pathway of photosynthesis in Mesembryanthemum
      crystallinum. 

PMID- 24458667
TI  - Studies on the action of abscisic acid on IAA-induced rapid growth of Avena
      coleoptile segments.
AB  - A linear displacement transducer has been used to monitor the growth of a column
      of Avena coleoptile segments in flowing solution. IAA at 10(-5)M in phosphate
      buffer of pH7 promotes growth after a latent period of 10.9 min, the initial
      maximum growth rate occurring after 25 min. Simultaneous treatment with 10(-5) M
      ABA does not affect either the latent period or the initial maximum growth rate
      in response to the IAA treatment, but subsequently gives rise to an inhibition of
      growth detectable after 30 min. In contrast, pretreatment with ABA for 100 min
      increases the duration of the latent period and reduces the initial maximum
      growth rate. Removal of the ABA rapidly relieves the inhibition of IAA-induced
      growth but a growth rate comparable to that of material treated only with IAA is
      never attained. Studies using 2-[(14)C]ABA and 1-[(14)C]IAA suggest that the
      latent period before ABA inhibition of growth is detectable is not due to a lag
      in ABA uptake, and that ABA is not acting by reducing IAA uptake. 

PMID- 24458668
TI  - [Pteroylglutamate derivatives in seedlings of Brassica napus oleifera].
AB  - The pteroylglutamate derivatives in Colza seedlings (Brassica napus) have been
      separated by chromatography on DEAE cellulose and determined by differential
      microbiological assay. A marked activity of formyl derivatives is confirmed by
      use of labelled folic acid, and the presence of several conjugated folates is
      shown. 

PMID- 24458669
TI  - Erratum.

PMID- 24458670
TI  - [Tunisian version validation of quality life's questionnaire for chronic
      inflammatory disease of intestine].
AB  - BACKGROUND: The systematic evaluation of the quality of life is essential in the
      management of patients with chronic bowel disease ( IBD) inflammatory diseases.
      AIM: Translate in Tunisian Arabic dialect the English version of "inflammatory
      bowel disease questionnaire" (UK- IBDQ ) and validated by studying its
      psychometric validity, discriminative ability, reliability and sensitivity to
      change. METHODS: 80 Tunisian patients with IBD completed the Tunisian version of
      the IBDQ (T- IBDQ ) , a visual analog scale , the SF- 36, the Harvey- Bradshaw
      index for Crohn's disease , and the index Simple clinical colitis activity for
      ulcerative colitis. RESULTS: The T- IBDQ included in the final version 5 fields.
      The internal validity of the items was satisfactory for all patients. TIBDQ was
      correlated with scores of SF- 36, visual analog scale scores and indices of
      activity of IBD. T- IBDQ distinguish between active disease and inactive disease
      . He was also sensitive to changes in disease activity . CONCLUSION: We validated
      in this work a Tunisian dialect Arabic version of the IBDQ : T- IBDQ . Its
      validity, discriminative ability , reliability and sensitivity to change were
      demonstrated.

PMID- 24458671
TI  - [Bipolar disorder and criminality: a comparative study by gender].
AB  - BACKGROUND: Unlike schizophrenia, the impact of gender on the criminality of
      patients with bipolar disorder has received little attention. AIM: To estimate
      the sex ratio in relation to acts committed by forensic bipolar patients and
      evaluate the impact of gender on the characteristics of this crime. METHODS: A
      comparative study by gender, conducted at the psychiatric hospital Razi has
      included all patients with bipolar disorder hospitalized between 1990 and 2010
      after being relaxed for mental illness, owing to the Tunisian penal code.
      RESULTS: The total number of patients was 36 and the sex ratio of 3.5.A suicide
      history was four times more common in women. Alcohol abuse was found only in men.
      Relapses were more frequent in women (3.06 I year against 1.14 I year, p = 0.02).
      Rapid cycling and comorbid anxiety were noted only in female patients. Filicide
      and prostitution were committed exclusively by women, economic crimes and sexual
      assaults were the preserve of men. The male offenses were more impulsive and
      unpremeditated (p = 0.04). CONCLUSIONS: Although sex ratio is in favor of men,
      women's representation in the violence induced by bipolar disorder is
      significant, resulting, particularly during depressive phases, by serious and
      deadly acts. Preventive measures of acting out in bipolar patients must be
      supported and especially adapted to the genre

PMID- 24458672
TI  - [Henoch Schonlein nephrites in children : clinical features and outcome : about
      34 cases].
AB  - AIM: To describe epidemiological, clinical, histological aspects, treatment and
      outcome of Henoch-Schonlein nephrits in children. METHODS: A retrospective study
      was conducted on medical data of 34 patients with Henoch-Schonlein nephritis From
      January 1, 1996 to December 31, 2010 in the Pediatric Department of Charles
      Nicolle Hospital. RESULTS: Nephritis occured in 68,7%. The average patient age
      was 7 years 2 months and sex ratio was 0,6. Microscopic hematuria was noted in
      23,5%, moderate proteinuria with or without hematuria was observed in 20,5%.
      Nephrotic syndrome was noted in 29,5%; nephritic syndrome was associated to
      nephritic syndrome in 23,5%. Isolated hypertension was noted in one patient.
      Follow-up was 2 years 6 months. Remission was noted in 26 cases (76,4%) , minor
      urinary abnormalities in 7 cases (20,5%) and renal active disease in one case.
      Relapse was observed in 6 cases. CONCLUSION: Our study was characterized by the
      predominance of severe renal manifestations and low grade histological aspects as
      well as favourable outcome in most 90% of cases.

PMID- 24458673
TI  - [Smoking prevalence in A Mami hospital of Ariana: prospective study about 700
      health professionals].
AB  - BACKGROUND: smoking is one of the most serious threats to public health
      worldwide. Health structures are the cornerstone of each program against smoking
      , or some studies have shown a prevalence of smoking as high in hospitals than in
      the general population. Aim : To assess the prevalence of smoking, smoking
      behavior and attitudes of health professionals towards smoking within the A Mami
      Ariana Hospital METHODS: This is a cross-sectional survey conducted among 700
      health professionals (doctors, nurses, workers, technicians and administrative
      staff) in the first quarter of 2010, based on a detailed questionnaire containing
      15 closed-end items. RESULTS: The average age was 37 years and the sex ratio 0,5.
      Response rate to questionnaire was 81,4% and overall smoking prevalence 24,8%,
      five times higher in men (52,5% vs 9,8% p< 0,001). Smoking was greater among
      workers, night health professionals employees and employees of technical
      services, administration and intensive care services and only 13% among doctors.
      50% of the surveyed have already tried at least once to quit, twice as many women
      than men. Former smokers accounted for 5,5% of all health professionals.
      CONCLUSION: Although our hospital has been declared non-smoking area since 2009,
      75% of professionals continue to smoke at the scene of their work. Strengthening
      of existing measures against smoking as smoking bans in the hospital, and
      improving training of health professionals on the dangers of smoking and ways of
      weaning are needed now.

PMID- 24458674
TI  - [Management of ovarian endometriomas: intraperitoneal cystectomy versus
      fenestration and coagulation].
AB  - BACKGROUND: Ovarian endometriomas is a common condition among women of
      reproductive age and represents a major cost in terms of public health. Despite
      these implications for public health, it remains difficult to arrive at a
      consensus on the optimal surgical treatment. AIMS: To study the clinical and
      paraclinical characteristics of this pathology and to compare two major surgical
      techniques: the intraperitoneal cystectomy and fenestration -coagulation in terms
      of recurrence and prognosis for future fertility. METHODS: A retrospective study
      of 31 patients who underwent surgical treatment for ovarian endometrioma
      histologically proved. The study period covers 10 years from January 2000 to
      December 2009. RESULTS: Laparoscopy was performed in 27 patients. The
      endometrioma was located to the left side in 64% of cases. The main strategy
      performed is intraperitoneal cystectomy in 18 patients (58.8%). In second place
      we find the fenestration-coagulation. The mean duration of postoperative follow
      up is 10.3 months. The recurrence of the cyst and the persistence of pain
      symptoms were significantly less frequent in the group of patients who underwent
      intraperitoneal cystectomy. CONCLUSION: The laparoscopic surgery remains the
      first line approach in terms of ovarian endometrioma.Cystectomy offers
      performance equal or superior to the fenestration-coagulation technique, and
      exposes to fewer recurrences. For these reasons, it should be recommended. The
      fenestration-coagulation is possible in case the cystectomy is difficult or
      incomplete.

PMID- 24458676
TI  - [Evaluation of urinary metanephrines for the diagnosis of pheochromocytoma].
AB  - OBJECTIVE: evaluate the assay of urinary metanephrines in diagnosis of
      pheochromocytoma (PH) and determine diagnostic cut-off values. METHODS: this is a
      retrospective study about 87 patients suspected of pheochromocytoma,whose of 24-h
      urinary fractionated metanephrine was measured. These cases were collected from
      Internal Medecine Departments (A and B) at Charles Nicolle's Hospital. Two groups
      of patients were studied: a pheochromocytoma group (n=33) with a histologically
      proven pheochromocytoma and a control group of 54 patients. Receiver Operating
      Characteristic (ROC) curves were used to determine the best sensitivities and
      specificities. RESULTS: The analysis of biological parameters showed that means
      and standard deviation of urinary fractionated metanephrines in pheochromocytoma
      group were significantly higher than those of control group. Sensitivity and
      specificity of urinary normetanephrine test (95% and 98.1% respectively) were
      higher than those of urinary metanephrine and 3-methoxytyramine. A correlation
      between urinary normetanephrine and tumor size of pheochromocytoma was found.
      CONCLUSION: Urinary fractionated metanephrines is an efficient biochemical test
      for the diagnosis of pheochromocytoma.

PMID- 24458675
TI  - [Pediatric Crohn's disease in Tunisia].
AB  - Crohn's disease occur mainly in adults. However, pediatric onset forms are not
      rare and have many characteristics. AIM: to study clinical, diagnostic,
      therapeutic and evolutive characteristics of crohn's disease in tunisian
      children. METHODS: Retrospective multicenter study conducted in 10 pediatric
      departments on a period of 10 years (2000-2008) RESULTS : 43 children were
      included. The sex-ratio was 1.68. The mean age at the onset of the symptoms was
      11+/-2.3 years (5-16 years). The age of onset was inferior to 10 years in 25 % of
      the children. The delay before management was superior to 1 year in 25% of cases.
      The initial symptoms were dominated by diarrhea (95%). Perineal manifestations
      were present at diagnosis in 30% of children and extra-digestive manifestations
      in 53%. Ileocolonic localization was the most frequent (46%). The initial disease
      flare was moderate in 83% of cases. The treatment was medical in 77 % of cases,
      nutritional and medical in 18.5%. Maintenance therapy was instituted in 86% of
      cases and consisted essentially in azathioprin (62%). The mean follow-up was 3
      years and 4 months. 60% of the children had at least one acute flare. During
      evolution, 7% of children had anoperineal surgery and 11% an intestinal
      resection. CONCLUSION: Crohn's disease seems rare in Tunisia. The time of
      diagnosis is often delayed. The management is based on immunosuppressive therapy
      and nutritional support.

PMID- 24458677
TI  - [Violence in schizophrenia: a study of 60 cases].
AB  - BACKGROUND: Epidemiological studies suggest a positive but controversial
      correlation between the major mental disorders, particularly schizophrenia and
      delinquent or criminal acting out. aim : To study the occurrence of violence in
      patients with schizophrenia according to demographic, clinical and disease
      progression features. METHODS: This retrospective study included all out
      patients, consulting during a period of one month, suffering from schizophrenia
      for at least five years. The clinical and forensic history was obtained owing to
      a semi-structured interview with patients and their families, medical records and
      the passing of different scales. RESULTS: Sixty patients were included. 46.7%
      (n=28) of patients had a violent behavior in the pre morbid period.
      Aggressiveness was noted as the first prodrome in 13.3% (n=8) of cases. 28 major
      acts of violence were committed by 30% (n=18) of patients regardless of the
      active period of disease. In 13.3% (n=8) of cases, these acts announced the
      disease. The majority of acts have been committed against a non-foreign person.
      Recurrence was noted in 44.4% (n=8) of patients. Several risk factors of violent
      behavior were found. Only prodromal aggression was associated with a poor
      prognosis. CONCLUSION: Violences committed by patients with schizophrenia are
      attributed to a particular group of patients and do not have necessarily a
      pejorative prognostic value.

PMID- 24458678
TI  - Pulmonary aneurysms in Behcet disease completely resolved after medical therapy.

PMID- 24458679
TI  - Urinary peritonitis caused by gangrenous cystitis.

PMID- 24458680
TI  - Systemic lupus erythematosus and psoriasis: a new case.

PMID- 24458681
TI  - [Non AA amyloidosis and sarcoidosis revealed by an aggressive angiomyxoma of the
      pelvis. Rare association].

PMID- 24458682
TI  - Calcific constrictive pericarditis.

PMID- 24458683
TI  - Case report of a patient presenting both schizophrenia and Charcot-Marie-Tooth
      disease.

PMID- 24458684
TI  - [Primitive pancreatic Cell B lymphoma: a case report].

PMID- 24458685
TI  - [Raynaud's syndrome revealing hypereosinophilic syndrome].

PMID- 24458686
TI  - A pyeloduodenal fistula. Report of case.

PMID- 24458687
TI  - Myocarditis mimicking an acute coronary syndrome.

PMID- 24458688
TI  - Treatment of tuberous xanthomas using carbon dioxide laser.

PMID- 24458689
TI  - Liver cirrhosis localized in the left lobe: an unusual presentation of small duct
      primary sclerosing cholangitis.

PMID- 24458691
TI  - Systematic screening for distress in oncology practice using the Distress
      Barometer: the impact on referrals to psychosocial care.
AB  - PURPOSE: This study evaluates how patterns of psychosocial referral of patients
      with elevated distress differ in a 'systematic screening for distress' condition
      versus a 'usual practice' condition in ambulatory oncology practice. METHODS: The
      psychosocial referral process in a 2-week usual practice (N=278) condition was
      compared with a 2-week 'using the Distress Barometer as a screening instrument'
      (N=304) condition in an outpatient clinic with seven consulting oncologists.
      RESULTS: Out of all distressed patients in the usual practice condition, only
      5.5% of patients detected with distress were actually referred to psychosocial
      counselling, compared with 69.1% of patients detected with distress in the
      condition with systematic screening using the Distress Barometer. Only 3.7% of
      patients detected with distress in the usual practice condition finally accepted
      this referral, compared with 27.6% of patients detected with distress in the
      screening condition. CONCLUSIONS: Using the Distress Barometer as a self-report
      screening instrument prior to oncological consultation optimises detection of
      elevated distress in patients, and this results in a higher number of performed
      and accepted referrals, but cannot by itself guarantee actual psychosocial
      referral or acceptance of referral. There is not only a problem of poor detection
      of distress in cancer patients but also a need for better decision-making and
      communication between oncologists and patients about this issue.

PMID- 24458692
TI  - Modelling the potential distribution of Bemisia tabaci in Europe in light of the
      climate change scenario.
AB  - BACKGROUND: Bemisia tabaci is a serious pest of agricultural and horticultural
      crops in greenhouses and fields around the world. This paper deals with the
      distribution of the pest under field conditions. In Europe, the insect is
      currently found in coastal regions of Mediterranean countries where it is subject
      to quarantine regulations. To assess the risk presented by B. tabaci to Europe,
      the area of potential establishment of this insect, in light of the climate
      change scenario, was assessed by a temperature-dependent physiologically based
      demographic model (PBDM). RESULTS: The simulated potential distribution under
      current climate conditions has been successfully validated with the available
      field records of B. tabaci in Europe. Considering climate change scenarios of +1
      and +2  degrees C, range expansion by B. tabaci is predicted, particularly in
      Spain, France, Italy, Greece and along the Adriatic coast of the Balkans.
      Nonetheless, even under the scenario of +2  degrees C, northern European
      countries are not likely to be at risk of B. tabaci establishment because of
      climatic limitations. CONCLUSION: Model validation with field observations and
      evaluation of uncertainties associated with model parameter variability support
      the reliability of model results. The PBDM developed here can be applied to other
      organisms and offers significant advantages for assessing the potential
      distribution of invasive species.

PMID- 24458693
TI  - Modulation of angiogenesis by thyroid hormone and hormone analogues: implications
      for cancer management.
AB  - Acting via a cell surface receptor on integrin alphavbeta3, thyroid hormone is
      pro-angiogenic. Nongenomic mechanisms of actions of the hormone and hormone
      analogues at alphavbeta3 include modulation of activities of multiple vascular
      growth factor receptors and their ligands (vascular endothelial growth factor,
      basic fibroblast growth factor, platelet-derived growth factor, epidermal growth
      factor), as well as of angiogenic chemokines (CX3 family). Thyroid hormone also
      may increase activity of small molecules that support neovascularization
      (bradykinin, angiotensin II) and stimulate endothelial cell motility. Therapeutic
      angio-inhibition in the setting of cancer may be opposed by endogenous thyroid
      hormone, particularly when a single vascular growth factor is the treatment
      target. This may be a particular issue in management of aggressive or recurrent
      tumors. It is desirable to have access to chemotherapies that affect multiple
      steps in angiogenesis and to examine as alternatives in aggressive cancers the
      induction of subclinical hypothyroidism or use of antagonists of the alphavbeta3
      thyroid hormone receptor that are under development. 

PMID- 24458694
TI  - Optical quantitative pathology of cervical intraepithelial neoplasia in human
      tissues using spatial frequency analysis.
AB  - An optical quantitative histological method in human tissues using spatial
      frequencies is demonstrated. Optical spatial frequency spectra from different
      stages of human Cervical Intraepithelial Neoplasia (CIN) tissue are evaluated as
      a potential quantitative pathological tool. The degree of randomness of tissue
      structures from normal to different stages of CIN tissue can be recognized by
      spatial frequency analysis. The standard deviation, sigma of human normal and CIN
      tissue, is obtained by assuming the spatial frequency spectra as a Gaussian
      distribution. A support vector machine classifier (SVM) is trained in the
      subspace of sigma. Twenty-eight normal and CIN samples of varying grades are
      examined and compared with current diagnostic outcomes. Our results suggest that
      an excellent accuracy for diagnostic purposes can be achieved. This approach
      offers a simple, efficient and objective way to supplement histopathology in
      recognizing alterations from normal to different stages of cervical pre-cancer,
      which are reflected by spatial information contained within the aperiodic and
      random structures of the different types of tissue.

PMID- 24458695
TI  - Hypoglycemia in Prader-Willi syndrome.
AB  - Although mouse models of Prader-Willi syndrome (PWS) suggest that hypoglycemia
      may be part of this syndrome, review of the literature shows little evidence that
      it is an issue in humans with PWS. Both adrenal and growth hormone deficiency can
      be seen in PWS, and both of these hormone deficiencies are associated with
      increased risk for hypoglycemia. We reviewed medical records for patients with
      PWS seen at the University of Florida Prader-Willi Program. Children were 2
      months to 5 years of age. We recorded the presence, degree, and persistence of
      hypoglycemia, age of first occurrence, genetic diagnosis, and gestational age.
      Repeated hypoglycemia was determined if individuals had multiple blood glucose
      (BG) values <50 mg/dl before 1 month old, or BG levels <50 mg/dl once and
      additional BG values <70 mg/dl after 1 year of age. Of 95 patient charts
      reviewed, 12 (12.6%) had recorded hypoglycemia. Six of 12 patients with
      hypoglycemia had documented BG levels <40 mg/dl. Seven had their first episode of
      hypoglycemia within the first day of life. Of these seven individuals, five had
      BG <40 mg/dl. Repeated hypoglycemia was noted in 10 patients (83% of all patients
      with hypoglycemia). Only two with hypoglycemia had documented adrenal
      insufficiency. Our study suggests that infants with PWS may be predisposed to
      hypoglycemia from birth. Additional investigation is necessary to confirm our
      findings and define the cause of hypoglycemia. If the presence of hypoglycemia is
      confirmed, early detection and treatment may result in improved neurocognitive
      outcomes.

PMID- 24458696
TI  - The effect of light quality and gibberellic acid (GA3) on photosynthesis and
      respiration rates of pea seedlings.
AB  - CO2 exchange were measured on pea seedlings (Pisum sativum L. var. Bordi)
      cultivated from seeds imbibed either in water (C-plants) or in gibberellic acid
      (GA3) at the concentration of 25 MUg/1 (GA-plants), and then grown under 17
      W/m(2) blue light (B-plants) or 11 W/m(2) red light (R-plants).When measured
      under the same light conditions as during growth the net photosynthesis (APS)
      rate in B-plants was about twice higher than that in R-plants. Dark respiration
      (DR) rate was 70% higher in B- than in R-plants. Red light retarded the
      development of photosynthetic activity, but GA3 suppressed this effect. The
      hormone enhanced net photosynthesis and dark respiration to the same extent.When
      measured under saturating white light net photosynthesis rate of C-plants was
      also two times higher in B-plants than in R-plants. Growth conditions had only a
      slight effect on the APS of GA-plants under white light. APS rates of GA-plants
      grown under red light were higher under white light than those of C-plants, but
      lower than those of plants grown under blue light.We assume that blue light
      induced formation of plants that were adapted to higher light intensity: red
      light had an opposite effect, whereas gibberellic acid induced formation of
      plants that were adapted to medium light intensity. 

PMID- 24458697
TI  - Involvement of thiol groups in the activity of phosphoenolpyruvate carboxylase
      from maize leaves.
AB  - Purified maize leaf phosphoenolpyruvate carboxylase (EC 4.1.1.31) was completely
      inactivated by several thiol-modifying reagents, including, CuCl2, CdCl2 and N
      ethylmaleimide. The inactivation by CuCl2 could be reversed by dithiothreitol,
      suggesting the involvement of vicinal dithiols in the inactivation
      process.Complete inactivation of phosphoenolpyruvate carboxylase was correlated
      with the incorporation of two mol ((3)H)N-ethylmaleimide per 100-kilodalton
      subunit. The total protection of the enzyme against N-ethylmaleimide inactivation
      afforded by the substrate, phosphoenolpyruvate, was correlated with the
      protection of one mol ((3)H)N-ethylmaleimide reactive residue per mol subunit.The
      complete inactivation of phosphoenolpyruvate carboxylase by N-ethylmaleimide and
      the protection afforded by phosphoenolpyruvate against modification suggest the
      presence of an essential cysteine residue in the catalytic site of the C4 leaf
      enzyme. 

PMID- 24458698
TI  - Photosynthesis and successional status of Costa Rican rain forest trees.
AB  - Seven tree species from three different light environments in the wet lowland
      forests of Costa Rica were grown under controlled environment conditions to
      assess light related photosynthetic potentials. Light saturated photosynthesis
      rates were clearly related to light levels of the field environments. Mean
      saturated, net photosynthetic rates ranged from 6.8 to 11.3 to 27.7 MUmol m(-2)
      sec(-1) for plants from heavy shade, canopy light gaps and man-made clearings
      respectively. Light saturation of plants from clearings occurred at
      photosynthetic photon flux densities greater than 1000 MUmol m(-2) sec(-1)
      whereas plants from heavy shade environments became light saturated near 500
      MUmol m(-2) sec(-1). Plants that normally occur in intermediate light
      environments were intermediate in light saturation levels. Mean maximum stomatal
      conductances ranged from 1.0 to 7.3 mm sec(-1) and followed a pattern similar to
      photosynthetic rates. 

PMID- 24458699
TI  - Influence of differences in leaf anatomy on net photosynthetic rates of some
      cultivars of Cassava.
AB  - Gas exchange measurements and leaf anatomy of 10 cassava cultivars were conducted
      to study the interrelationship between the relatively high photosynthetic rates
      and the factors limiting internal CO2 diffusion. The internal mesophyll surface
      area per unit leaf surface area (A(mes)/A) and the intracellular components of
      CO2 diffusion and fixation resistance (R(cell)CO2) were determined. Among the
      group of cultivars tested net CO2 exchange rates were 26+/-2.5 MUmol CO2 m(-2) s(
      1) in normal air and intense light and A(mes)/A ranged from 14 to 38. Estimated
      R(cell)CO2 ranged from 4300 to 13,000 s m(-1). The combined and compensating
      effects of A(mes)/A and R(cell)CO2 accounted for both the high net photosynthetic
      rates (Pn) and the lack of large differences in Pn among cultivars. 

PMID- 24458700
TI  - Photosynthetic responses of cassava cultivars (Manihot esculenta Crantz) from
      different habitats to temperature.
AB  - Maximum photosynthetic CO2 exchange rates (Pn) of single attached leaves were
      determined for several cassava cultivars selected from different habitats and
      grown in pots outdoors at CIAT, Colombia, S.A. Pn rates were in a narrow range of
      22 to 26 MUmol CO2 m(-2)s(-1) for all cultivars tested when measured at high
      photon flux density, normal air, optimum temperature and with low leaf-air vapor
      pressure differences. For all tested cultivars (9 cvs.), there was a broad
      optimum temperature for Pn between 25 to 35 degrees C. At temperatures below and
      above this range Pn declined in all cultivars with Pn rates reaching 80% of
      maximum at 20 and 40 degrees C. Pn temperature coefficient (Q10) from 15-25
      degrees C was 1.6+/-0.2 across cultivars. No consistent relation existed between
      Pn, optimum temperature, and the original habitat. 

PMID- 24458701
TI  - Effect of irradiance during growth of Glycine max on photosynthetic capacity and
      percent activation of ribulose 1,5-bisphosphate carboxylase.
AB  - The initial (in vivo) and total (activity present after preincubation with CO2
      and Mg(2+)) activities of ribulose bisphosphate carboxylase were both assayed in
      extracts of leaves of soybean (Glycine max) plants which had been grown under 4
      different irradiance levels. The total carboxylase activity per unit leaf area
      decreased with decreased irradiance during growth but was not different on a dry
      weight basis. The initial activity as a percentage of the total activity was
      unchanged (approximately 95%) except in leaves of plants grown at the lowest
      irradiance (74%). When the plants grown at the lowest irradiance were exposed to
      high irradiance, the initial activity was increased to 93% of the total. Light
      saturated rates of photosynthesis per unit leaf area were lower and saturated at
      lower irradiance for plants grown at lower irradiances. Initial carboxylase
      activity was correlated closely (r(2)=0.84) with leaf photosynthesis rate on a
      dry weight basis. 

PMID- 24458702
TI  - The role of a long-wavelength pigment form in the chlorophyll biosynthesis.
AB  - Photoconversion of protochlorophyllide650 form was observed in etiolated leaves
      illuminated with long-wavelength-690 nm-light. This process showed Shibata shift
      and was found to have a strong temperature dependence between 20 and -40 degrees
      C. The low rate of reaction, the strong temperature dependence and calculations
      on the spectral overlap integral of absorption and fluorescence bands in this
      spectral region indicate that the phototransformation of the 650 nm form of
      protochlorophyllide may be caused by a back energy migration from a long
      wavelength pigment form absorbing around 690 nm; this pigment form is probably a
      long-wavelength form of protochlorophyll/ide. 

PMID- 24458703
TI  - Pyrokinin/PBAN-like peptides in the central nervous system of mosquitoes.
AB  - The pyrokinin/pheromone biosynthesis activating neuropeptide (PBAN) family of
      peptides is characterized by a common C-terminal pentapeptide, FXPRLamide, which
      is required for diverse physiological functions in various insects. Polyclonal
      antisera against the C-terminus was utilized to determine the location of cell
      bodies and axons in the central nervous systems of larval and adult mosquitoes.
      Immunoreactive material was detected in three groups of neurons in the
      subesophageal ganglion of larvae and adults. The corpora cardiaca of both larvae
      and adults contained immunoreactivity indicating potential release into
      circulation. The adult and larval brains had at least one pair of immunoreactive
      neurons in the protocerebrum with the adult brain having additional
      immunoreactive neurons in the dorsal medial part of the protocerebrum. The
      ventral ganglia of both larvae and adults each contained one pair of neurons that
      sent their axons to a perisympathetic organ associated with each abdominal
      ganglion. These results indicate that the mosquito nervous system contains
      pyrokinin/PBAN-like peptides and that these peptides could be released into the
      hemolymph. The peptides in insects and mosquitoes are produced by two genes, capa
      and pk/pban. Utilizing PCR protocols, we demonstrate that products of the capa
      gene could be produced in the abdominal ventral ganglia and the products of the
      pk/pban gene could be produced in the subesophageal ganglion. Two receptors for
      pyrokinin peptides were differentially localized to various tissues.

PMID- 24458704
TI  - Neck swellings.

PMID- 24458706
TI  - Paternal isodisomy of chromosome 5 in a patient with recessive multiple
      epiphyseal dysplasia.

PMID- 24458707
TI  - Zn2+-regulated self-sorting and mixing of phosphates and carboxylates on the
      surface of functionalized gold nanoparticles.
AB  - Herein, we describe the self-sorting of phosphate- and carboxylate-containing
      molecules on the surface of monolayer-protected gold nanoparticles. Self-sorting
      is driven by selective interactions between the phosphate probe and Zn(2+)
      complexes in one monolayer; these interactions force the carboxylate probe to
      move to a second type of nanoparticle. This process effectively separates the
      probes and causes their localization in well-defined spaces surrounding the
      nanoparticles. The removal/addition of Zn(2+) metal ions from the system is used
      to convert the system from an ordered to a disordered state and vice versa. The
      possibility to control the location and transport of populations of molecules in
      a complex mixture creates new perspectives for the development of innovative
      complex catalytic systems that mimic nature. 

PMID- 24458708
TI  - Role of SN1 lipases on plasma lipids in metabolic syndrome and obesity.
AB  - OBJECTIVE: To assess the phospholipase activity of endothelial (EL) and hepatic
      lipase (HL) in postheparin plasma of subjects with metabolic syndrome
      (MS)/obesity and their relationship with atherogenic and antiatherogenic
      lipoproteins. Additionally, to evaluate lipoprotein lipase (LPL) and HL activity
      as triglyceride (TG)-hydrolyses to complete the analyses of SN1 lipolytic enzymes
      in the same patient. APPROACH AND RESULTS: Plasma EL, HL, and LPL activities were
      evaluated in 59 patients with MS and 36 controls. A trend toward higher EL
      activity was observed in MS. EL activity was increased in obese compared with
      normal weight group (P=0.009) and was negatively associated with high-density
      lipoprotein-cholesterol (P=0.014 and P=0.005) and apolipoprotein A-I (P=0.045 and
      P=0.001) in control and MS group, respectively. HL activity, as TG-hydrolase, was
      increased in MS (P=0.025) as well as in obese group (P=0.017); directly
      correlated with low-density lipoprotein-cholesterol (P=0.005) and apolipoprotein
      B (P=0.003) and negatively with high-density lipoprotein-cholesterol (P=0.021) in
      control group. LPL was decreased in MS (P<0.001) as well as in overweight and
      obese compared with normal weight group (P=0.015 and P=0.004, respectively);
      inversely correlated %TG-very low-density lipoproteins (P=0.04) and
      TG/apolipoprotein B index (P=0.013) in control group. These associations were not
      found in MS. CONCLUSIONS: We describe for the first time EL and HL activity as
      phospholipases in MS/obesity, being both responsible for high-density lipoprotein
      catabolism. Our results elucidate part of the remaining controversies about SN1
      lipases activity in MS and different grades of obesity. The impact of insulin
      resistance on the activity of the 3 enzymes determines the lipoprotein
      alterations observed in these states.

PMID- 24458709
TI  - Body mass index and height from infancy to adulthood and carotid intima-media
      thickness at 60 to 64 years in the 1946 British Birth Cohort Study.
AB  - OBJECTIVE: Atherosclerosis begins early in life and obesity is a key determinant.
      We investigated the role of body mass index (BMI) and height from infancy to
      adulthood in presenting with high adulthood carotid intima-media thickness.
      APPROACH AND RESULTS: Odds ratios of BMI, and height Z scores at 2, 4, 6, 7, 11,
      15, and 20 years, and changes between 2 and 4, 4 and 7, 7 and 15, and 15 and 20
      years, for carotid intima-media thickness at 60 to 64 years in the upper quartile
      were estimated for 604 men and 669 women. Confounding by early-life environments,
      mediating by body size and cardiometabolic measures at 60 to 64 years, and effect
      modification were investigated. In men, there was positive association of BMI at
      4 years (odds ratio, 1.256; 95% confidence interval, 1.026-1.538) and 20 years
      (1.282; 1.022-1.609), negative association of height at 4 years (0.780; 0.631
      0.964), and negative association of height growth between 2 and 4 years (0.698;
      0.534-0.913) with high carotid intima-media thickness. The childhood estimates
      were robust, but the estimate for BMI at 20 years was attenuated by adjustment
      for BMI at 60 to 64 years. The protective influence of greater early childhood
      height was strongest in those with the lowest systolic blood pressure at 60 to 64
      years. In women, there was no pattern of association and all confidence intervals
      crossed 1. CONCLUSIONS: Early childhood in men might be a sensitive developmental
      period for atherosclerosis, in which changes in BMI and height represent 2
      distinct biological mechanisms. The maintenance of healthy weight in men from
      adolescence onward may be a useful strategy to avoid the atherosclerotic
      complications of adiposity tracking.

PMID- 24458710
TI  - Macrophages control vascular stem/progenitor cell plasticity through tumor
      necrosis factor-alpha-mediated nuclear factor-kappaB activation.
AB  - OBJECTIVE: Vascular lineage differentiation of stem/progenitor cells can
      contribute to both tissue repair and exacerbation of vascular diseases such as in
      vein grafts. The role of macrophages in controlling vascular progenitor
      differentiation is largely unknown and may play an important role in graft
      development. This study aims to identify the role of macrophages in vascular
      stem/progenitor cell differentiation and thereafter elucidate the mechanisms that
      are involved in the macrophage- mediated process. APPROACH AND RESULTS: We
      provide in vitro evidence that macrophages can induce endothelial cell (EC)
      differentiation of the stem/progenitor cells while simultaneously inhibiting
      their smooth muscle cell differentiation. Mechanistically, both effects were
      mediated by macrophage-derived tumor necrosis factor-alpha (TNF-alpha) via TNF
      alpha receptor 1 and canonical nuclear factor-kappaB activation. Although the
      overexpression of p65 enhanced EC (or attenuated smooth muscle cell)
      differentiation, p65 or TNF-alpha receptor 1 knockdown using lentiviral short
      hairpin RNA inhibited EC (or rescued smooth muscle cell) differentiation in
      response to TNF-alpha. Furthermore, TNF-alpha-mediated EC differentiation was
      driven by direct binding of nuclear factor-kappaB (p65) to specific VE-cadherin
      promoter sequences. Subsequent experiments using an ex vivo decellularized vessel
      scaffold confirmed an increase in the number of ECs and reduction in smooth
      muscle cell marker expression in the presence of TNF-alpha. The lack of TNF-alpha
      in a knockout mouse model of vein graft decreased endothelialization and
      significantly increased thrombosis formation. CONCLUSIONS: Our study highlights
      the role of macrophages in directing vascular stem/progenitor cell lineage
      commitment through TNF-alpha-mediated TNF-alpha receptor 1 and nuclear factor
      kappaB activation that is likely required for endothelial repair in vascular
      diseases such as vein graft.

PMID- 24458712
TI  - Shear-sensitive regulation of neutrophil flow behavior and its potential impact
      on microvascular blood flow dysregulation in hypercholesterolemia.
AB  - OBJECTIVE: Shear stress-induced pseudopod retraction is an anti-inflammatory
      measure that minimizes neutrophil activity and is regulated by membrane
      cholesterol. We tested the hypothesis that a hypercholesterolemic impairment of
      shear mechanotransduction alters the neutrophil flow behavior leading to
      microvascular dysfunction. APPROACH AND RESULTS: We examined the shear effects on
      the flow behavior of human leukocytes. When subjected to shearing during cone
      plate viscometry, leukocyte suspensions exhibited parallel time-dependent
      reductions in viscosity and pseudopod activity. Shear-induced reductions in
      suspension viscosity were attenuated by membrane cholesterol enrichment. We also
      showed that enhanced pseudopod activity of leukocyte suspensions in 10%
      hematocrit significantly (P<0.05) raised the flow resistance of microvascular
      mimics. These results implicate an impaired neutrophil pseudopod retraction
      response to shear in hypercholesterolemic microvascular dysfunction. We confirmed
      this using near-infrared diffuse correlation spectroscopy to assess skeletal
      muscle blood flow regulation in the hindlimbs of mice subjected to reactive
      hyperemia. Using a custom protocol for the mouse, we extrapolated an adjusted
      peak flow and time to adjusted peak flow to quantify the early phase of the blood
      flow recovery response during reactive hyperemia when shear mechanobiology likely
      has a maximal impact. Compared with mice on normal diet, hypercholesterolemic
      mice exhibited significantly (P<0.05) reduced adjusted peak flow and prolonged
      time to adjusted peak flow which correlated (r=0.4 and r=-0.3, respectively) with
      neutrophil shear responsiveness and were abrogated by neutropenia. CONCLUSIONS:
      These results provide the first evidence that the neutrophils contribute to
      tissue blood flow autoregulation. Moreover, a deficit in the neutrophil
      responsiveness to shear may be a feature of hypercholesterolemia-related
      microvascular dysfunction.

PMID- 24458711
TI  - Interleukin 1 receptor 1 and interleukin 1beta regulate megakaryocyte maturation,
      platelet activation, and transcript profile during inflammation in mice and
      humans.
AB  - OBJECTIVE: Interleukin 1 Receptor 1 (IL1R1) and its ligand, IL1beta, are
      upregulated in cardiovascular disease, obesity, and infection. Previously, we
      reported a higher level of IL1R1 transcripts in platelets from obese individuals
      of the Framingham Heart Study (FHS), but its functional effect in platelets has
      never been described. Additionally, IL1beta levels are increased in
      atherosclerotic plaques and in bacterial infections. The aim of this work is to
      determine whether IL1beta, through IL1R1, can activate platelets and
      megakaryocytes to promote atherothrombosis. APPROACH AND RESULTS: We found that
      IL1beta-related genes from platelets, as measured in 1819 FHS participants, were
      associated with increased body mass index, and a direct relationship was shown in
      wild-type mice fed a high-fat diet. Mechanistically, IL1beta activated nuclear
      factor-kappaB and mitogen-activated protein kinase signaling pathways in
      megakaryocytes. IL1beta, through IL1R1, increased ploidy of megakaryocytes to 64+
      N by 2-fold over control. IL1beta increased agonist-induced platelet aggregation
      by 1.2-fold with thrombin and 4.2-fold with collagen. IL1beta increased adhesion
      to both collagen and fibrinogen, and heterotypic aggregation by 1.9-fold over
      resting. High fat diet-enhanced platelet adhesion was absent in IL1R1(-/-) mice.
      Wild-type mice infected with Porphyromonas gingivalis had circulating heterotypic
      aggregates (1.5-fold more than control at 24 hours and 6.2-fold more at 6 weeks)
      that were absent in infected IL1R1(-/-) and IL1beta(-/-) mice. CONCLUSIONS: In
      summary, IL1R1- and IL1beta-related transcripts are elevated in the setting of
      obesity. IL1R1/IL1beta augment both megakaryocyte and platelet functions, thereby
      promoting a prothrombotic environment during infection and obesity; potentially
      contributing to the development of atherothrombotic disease.

PMID- 24458714
TI  - Glenohumeral relationship in maximum elevation.
AB  - PURPOSE: The purpose of this study was to clarify rotational relationships
      between the anatomical landmarks of the glenohumeral joint in maximum elevation.
      METHODS: Twenty-five healthy volunteers (20 men, 5 women; mean age, 31 years)
      held the arm in maximum elevation in an open MRI system. In each three
      dimensionally computer-generated image, elevation angle of the humerus in the
      plane of elevation was measured, based on the glenoid and the scapular planes.
      Using the equator set on the head surface by the plane parallel to the humeral
      axis, involving the head center and the bicipital groove, glenoid location and
      rotational relationships were investigated. RESULTS: The elevation angle was 102
      degrees  +/- 9 degrees  in the plane 7 degrees  +/- 8 degrees  anterior to the
      scapular plane, and axial rotation was fixed with the glenoidal long axis
      parallel to the equator (within 2 degrees ). Each glenoid center located on
      antero-superior portion of the humeral head, and the direction from the top of
      the head to its location was the same as that of the shaft tilting, indicating
      the glenoid only translated without rotation after reaching the top of the head
      on the equator. CONCLUSIONS: Before reaching maximum elevation, the glenohumeral
      joint would be locked in axial rotation. The position when the glenoid is on the
      top of the humeral head with the humeral shaft perpendicular to the glenoid is
      considered to be essentially the final position of elevation, above which the
      glenohumeral joint only translates without axial rotation even if the humerus is
      more elevated.

PMID- 24458715
TI  - The influence of root temperature on (14)C assimilate profiles in wheat roots.
AB  - The rate of translocation of (14)C assimilates from leaves to seminal roots in
      wheat seedlings was considerably reduced by lowering root temperature from 20
      degrees  to 10 degrees  or 5 degrees  although the total translocation of (14)C
      to the roots after 24 h was little affected by temperature. The lowered root
      temperatures (particularly 5 degrees ) resulted in a more uniform distribution of
      assimilate along the roots than did a temperature of 20 degrees , the ratios of
      radioactivity/cm in the apical cm, elongating zone, and basal parts of the root
      after 24 h being 14.0:9.6:1 in 20 degrees  roots by contrast with 2.8:1:1 in 5
      degrees  roots. Temperature effects on assimilate distribution may help explain
      the observations that for roots grown below 15 degrees  ion uptake is sustained
      in older parts and that roots grown at a low temperature are thicker than roots
      grown at a higher one. 

PMID- 24458713
TI  - Cytochrome P450 2C8 omega3-long-chain polyunsaturated fatty acid metabolites
      increase mouse retinal pathologic neovascularization--brief report.
AB  - OBJECTIVE: Regulation of angiogenesis is critical for many diseases.
      Specifically, pathological retinal neovascularization, a major cause of
      blindness, is suppressed with dietary omega3-long-chain polyunsaturated fatty
      acids (omega3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and
      lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs,
      producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase
      (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on
      neovascularization is unknown. APPROACH AND RESULTS: The mouse model of oxygen
      induced retinopathy was used to investigate retinal neovascularization. We found
      that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in
      oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased
      retinal epoxide:diol ratio. With a omega3LCPUFA-enriched diet, retinal
      neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice
      (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic
      acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the
      epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg).
      Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular
      development compared with their wild-type littermate controls. The proangiogenic
      role in retina of CYP2C8 with both omega3LCPUFA and omega6LCPUFA and
      antiangiogenic role of sEH in omega3LCPUFA metabolism were corroborated in aortic
      ring assays. CONCLUSIONS: Our results suggest that CYP2C omega3LCPUFA metabolites
      promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid
      metabolic pathway influencing retinal neovascularization.

PMID- 24458716
TI  - [Illumination Burst of CO2 and carbon dioxide inner reserves in Zea mays].
AB  - When a leaf of maize (Zea mays) is illuminated following a long enough period of
      darkness (t?10 min) under pure nitrogen, the oxygen evolution occurs only after a
      lag time from one to several minutes. During this delay, a burst of CO2 occurs
      the maximum of which corresponds to the start of oxygen evolution. The source of
      carbon dioxide is thought to be a stable internal CO2 reserve which has been
      previously formed in the leaf and is assumed to be malic acid. For as yet unknown
      reasons the carbon dioxide issued from the reserve by action of light at the
      beginning of illumination is not fixed and escapes into the atmosphere; this
      process could require the phytochrome system. 

PMID- 24458717
TI  - Cytokinins in Populus x robusta (schneid): Light effects on endogenous levels.
AB  - Cytokinin levels in both attached and detached mature leaves of poplar (Populus x
      robusta) increase transiently after short periods of exposure to red light. The
      degree and rapidity of response seems dependent on the physiological condition of
      the leaves. The cytokinin, 6-(2-hydroxybenzyl)amino purine riboside, specifically
      increases after red light treatment. Diurnal changes of leaf cytokinins occur,
      with a pronounced peak of activity being present at daybreak. 

PMID- 24458718
TI  - Developmental changes in the levels of SDS-extractable polypeptides during
      plastid morphogenesis.
AB  - A quantitative estimation of the levels of plastidic SDS-extractable polypeptides
      as separated by polyacrylamide gel electrophoresis is described to demonstrate
      the practicality of such an approach. Using an internal standard of cytochrome c
      and expressing all polypeptide levels as cytochrome c relative stain equivalents,
      the levels of most polypeptides from developing Avena plastids change relative to
      the period of greening especially over the period 12-20 h. Some changes in
      certain polypeptides can be shown to be due to plastid senescence rather than
      plastid development. There is also a distinct difference in the pattern of
      polypeptides when plastids are isolated from different laminar regions. An
      incubation study using etioplasts showed of the original 8 polypeptides, six were
      retained, two were lost, another two were formed during incubation but eleven
      polypeptides found in the in situ study never appeared. 

PMID- 24458719
TI  - Thigmomorphogenesis: The response of plant growth and development to mechanical
      stimulation : With special reference to Bryonia dioica.
AB  - When young plants of Hordeum vulgare. Bryonia dioica. Cucumis sativus. Phaseolus
      vulgaris. Mimosa pudica. and Ricinus communis. were given a gentle mechanical
      stimulus by rubbing the internodes for about 10 s once or twice daily, elongation
      was significantly retarded. Plants of Cucurbita pepo Pisum sativum and Triticum
      aestivum did not exhibit any such response. The initial response to rubbing was
      very rapid, elongation stopping less than 3 min after application of the
      stimulus. When the stimulus was discontinued after 7 days, elongation
      accelerated, reaching a normal or supernormal rate within 3 or 4 days. Mechanical
      stimulation also affected aspects of growth and development other than stem
      elongation. In Mimosa pudica, flower bud production was retarded, as was the
      growth of the tendrils, leaves, and petioles in Bryonia dioica. It is suggested
      that this response be called thigmomorphogenesis, and that it represents an
      adaptation designed to protect plants from the stresses produced by high winds
      and moving animals. Some evidence indicates that thigmomorphogenesis may be
      mediated by ethylene. 

PMID- 24458720
TI  - The metabolism of abscisic acid in relation to its reversible action on stomata
      in leaves of Hordeum vulgare L.
AB  - Barley leaves extracted 35 min after a 15-min pulse of 10(-6) M (14)C-labelled
      cis,trans-(+/-)-abscisic acid (ABA) showed very little breakdown of the ABA.
      Leaves extracted 2 h after a 30-min pulse of 10(-5) M labelled ABA showed at
      least 34% degradation of the hormone. The pattern of degradation was very similar
      for leaves kept in either light or darkness following the labelling pulse, and
      the products formed resembled those described in tomato fruit and bean axes. No
      detectable isomerization to the physiologically inactive trans,trans-(+/-)-ABA
      isomer occurred in these leaves during the 2-h period. ABA-induced stomatal
      closure is partially reduced 30 min after the pulse. The reversal cannot be
      attributed to catabolism of the hormone and must be explained by removal of the
      hormone into storage sites where it cannot act on the stomata. 

PMID- 24458721
TI  - Effects of cycloheximide, D-threo-chloramphenicol, erythromycin and actinomycin D
      on De-novo synthesis of cytoplasmic and mitochondrial proteins in the cotyledons
      of germinating pea seeds.
AB  - Inhibitors of, and radioactive substrates for, protein synthesis were introduced
      into germinating pea (Pisum sativum L.) seeds, and protein synthesis was allowed
      to proceed in vivo. Subsequent analyses of subcellular fractions showed the
      following: Cycloheximide strongly inhibited the incorporation of [(14)C]leucine
      into both mitochondrial and cytoplasmic proteins. D-Threo-chloramphenicol and
      erythromycin did not affect cytoplasmic protein synthesis, but partially
      inhibited mitochondrial protein synthesis. These results suggest that most of the
      new mitochondrial proteins were originally synthesized in the cytoplasm.
      Actinomycin D did not appreciably affect the initial incorporation of
      [(14)C]leucine into either mitochondrial or cytoplasmic proteins, suggesting that
      information (mRNA) concerning the initially synthesized proteins may be present
      in the quiescent seeds. The lack of appreciable incorporation of [(3)H]thymidine
      into mitochondrial DNA supported our previons report that mitochondria may not be
      synthesized de novo in pea cotyledons. 

PMID- 24458722
TI  - Physiological evidence for auxin-induced hydrogen-ion secretion and the epidermal
      paradox.
AB  - Peeled Avena coleoptile sections will respond to auxin only if the molarity of
      the incubation buffer at pH 6.2 is less than 5 mM. This inhibition of auxin
      induced growth is not due to toxicity or to a reduction of turgor below the
      critical value needed for extension but rather appears to be related simply to
      buffering capacity. These data therefore serve as physiological evidence that
      H(+)-secretion is an intregal part of auxin-induced cell wall loosening. Other
      data obtained utilizing peeled plant sections and epidermal strips suggest that
      the epidermis does not directly control cell extension growth. A model is
      proposed to explain the curvature response in split-segments tests in terms of a
      H(+) gradient across the section. As far as tested this model appears to be an
      alternative to an older concept which implied that the curvature phenomenon in
      split sections was mediated by special properties of the epidermal layer. Our
      results suggest that the curvature response may be more directly attributable to
      the presence of the cuticle. 

PMID- 24458723
TI  - Starch synthetase: Comparison of UDPG and ADPG as glucosyl donors in immature
      barley endosperm.
AB  - The activity of starch synthetase in developing barley endosperm was measured in
      amyloplasts and in the soluble endosperm fraction by incorporation of
      radioactively labelled glucose into starch. Both uridine diphosphate glucose
      (UDPG) and adenosine diphophate glucose (ADPG) were used as glucosyl donors.
      Enzyme activity was initially located in the soluble fraction, but increasing
      activity could be detected in the amyloplast fraction during endosperm
      maturation. 

PMID- 24458724
TI  - The effect of the anti-angiogenic drug sunitinib malate on the vascular
      architecture of oral squamous cell carcinoma.
AB  - The effects of anti-angiogenic therapies in guiding tumor angioarchitecture
      prompted us to examine the modifications in the vascular network of the oral
      squamous cell carcinoma (SCC) produced by the multitargeted tyrosine kinase
      inhibitor sunitinib malate. Twelve Syrian hamsters had their right buccal pouches
      submitted to tumor induction with dimethylbenzanthracene and carbamide peroxide
      for 55 days. The animals were then divided into two groups of six animals each;
      group I was treated with sunitinib malate and group II (control) was remained
      untreated. After 4 weeks, the hamsters had their vascular networks casted by
      Mercox(r) resin and analyzed by scanning electron microscopy. The qualitative
      study of the vascular network of the control tumor-bearing pouches showed images
      of intussusception and sprouting angiogenesis, flattened blood vessels, abrupt
      variations in their diameter, and a tortuous course. The samples treated with
      sunitinib exhibited a qualitative reduction of the signs of vascular
      proliferation. In addition, these casts presented an attenuation of the
      morphological features observed in the untreated tumor-bearing pouches.
      Quantitative analysis demonstrated that the pouches treated with sunitinib did
      not show a decrease (P > 0.05) in the vascular diameter and intervessel distances
      when compared with the control group. The results of the present study suggest
      that sunitinib may act on the vascular network of oral SCC, normalizing the blood
      vessels. However, further experiments should be performed in order to determine a
      judicious dose of this anti-angiogenic therapy.

PMID- 24458725
TI  - Normative data for female adolescents with eating disorders on the
      Multidimensional Anxiety Scale for Children.
AB  - OBJECTIVE: To provide normative data on the Multidimensional Anxiety Scale for
      Children (MASC) for female adolescents presenting for eating disorder (ED)
      treatment. METHOD: This study is part of the Helping to Outline Paediatric Eating
      Disorders Project registry (N ~ 1,000), a prospective ongoing registry study
      comprising consecutive pediatric tertiary ED referrals. Female adolescents (N =
      278; 13-17 years) with EDs completed the MASC at intake. RESULTS: Summary data
      including percentiles are given for the MASC total and subscales. MASC scores
      were higher than community norms as expected and increased with age (p <.001) and
      an anorexic spectrum diagnosis (p < .001). DISCUSSION: The norms reported will
      aid clinicians in the understanding and interpretation of individual MASC scores
      among female adolescents with EDs and could assist future research to better
      understand the role of anxiety in the onset and maintenance of EDs.

PMID- 24458726
TI  - Pneumothorax from subpleural blebs-a new association of sotos syndrome?
AB  - We describe two unrelated patients with molecularly confirmed Sotos syndrome with
      multiple subpleural blebs and pneumothorax. We propose this as a new association.
      Patient 1 is a 3-year-old boy with a 1.9 Mb interstitial deletion of the long arm
      of chromosome 5, with breakpoints at q35.2 and q35.3, encompassing NSD1 and
      Patient 2 is a 9-year-old girl with a de novo truncating mutation within NSD1.
      Both patients presented with sudden onset dyspnea due to a unilateral
      pneumothorax: Patient 1 at the age of 18 months and Patient 2 at 9 years. In
      both, the pneumothorax recurred following removal of the chest drain and, on
      further investigations, multiple subpleural blebs were identified necessitating a
      pleurodesis and tissue resection. This is the first report of multiple subpleural
      blebs leading to pneumothorax in association with Sotos syndrome. Given the
      similar and unusual presentation in the two affected patients, we suggest that
      this may be a real association, albeit a rare one. While screening would not be
      advocated for such a rare association, we recommend that clinicians consider
      pneumothorax in patients with Sotos syndrome and sudden onset of dyspnea and are
      aware that it may be refractory to first line treatment.

PMID- 24458727
TI  - Epitaxial growth of molecular crystals on van der waals substrates for high
      performance organic electronics.
AB  - Epitaxial van der Waals (vdW) heterostructures of organic and layered materials
      are demonstrated to create high-performance organic electronic devices. High
      quality rubrene films with large single-crystalline domains are grown on h-BN
      dielectric layers via vdW epitaxy. In addition, high carrier mobility comparable
      to free-standing single-crystal counterparts is achieved by forming interfacial
      electrical contacts with graphene electrodes. 

PMID- 24458728
TI  - Design it yourself (DIY): in-house instructional design for online pharmacology.
AB  - Demand for e-learning courses has risen dramatically placing pressure on
      institutions to offer more online courses. Third party vendors now offer courses
      that can be embedded directly into learning management systems. When
      transitioning from in-class to e-learning formats, instructors must decide
      whether to use commercially available courses or design in-house. The objective
      of this study was to evaluate our transition from delivering introductory
      pharmacology via a purchased e-pack to an in-house designed course. A team that
      included an instructional designer, an education specialist and a content expert
      created an online course in pharmacology. Merrill's first principles of
      instruction were used as a guide for the design of our online course. Where
      appropriate, multiple forms of media were introduced to reinforce concepts. We
      compared grades and design strategy from a previous iteration that was delivered
      using a commercially available e-pack. A cost analysis was conducted to determine
      the institutional setup and maintenance costs of in-house course design. The mean
      final grade from the in-house designed course was 81.9 (0.5) % compared to 76.4
      (0.5) % for the e-pack course (P < 0.001). Course evaluations were significantly
      improved for the in-house course compared to the e-pack. Cost-analysis
      demonstrated that designing a course in-house has a high initial cost
      ($111,180.57) but can be maintained with minimal institutional cost ($500) in
      future offerings. Our results demonstrate that effective courses can be designed
      in-house and this should be a viable option for institutions that have
      appropriate resources to support instructional design.

PMID- 24458729
TI  - Trifluoroacetic acid in 2,2,2-trifluoroethanol facilitates S(N)Ar reactions of
      heterocycles with arylamines.
AB  - Small-molecule drug discovery requires reliable synthetic methods for attaching
      amino compounds to heterocyclic scaffolds. Trifluoroacetic acid-2,2,2
      trifluoroethanol (TFA-TFE) is as an effective combination for achieving SN Ar
      reactions between anilines and heterocycles (e.g., purines and pyrimidines)
      substituted with a leaving group (fluoro-, chloro-, bromo- or alkylsulfonyl).
      This method provides a variety of compounds containing a "kinase-privileged
      fragment" associated with potent inhibition of kinases. TFE is an advantageous
      solvent because of its low nucleophilicity, ease of removal and ability to
      solubilise polar substrates. Furthermore, TFE may assist the breakdown of the
      Meisenheimer-Jackson intermediate by solvating the leaving group. TFA is a
      necessary and effective acidic catalyst, which activates the heterocycle by N
      protonation without deactivating the aniline by conversion into an anilinium
      species. The TFA-TFE methodology is compatible with a variety of functional
      groups and complements organometallic alternatives, which are often
      disadvantageous because of the expense of reagents, the frequent need to explore
      diverse sets of reaction conditions, and problems with product purification. In
      contrast, product isolation from TFA-TFE reactions is straightforward:
      evaporation of the reaction mixture, basification and chromatography affords
      analytically pure material. A total of 45 examples are described with seven
      discrete heterocyclic scaffolds and 2-, 3- and 4-substituted anilines giving
      product yields that are normally in the range 50-90 %. Reactions can be performed
      with either conventional heating or microwave irradiation, with the latter often
      giving improved yields. 

PMID- 24458730
TI  - Duct-to-duct reconstruction in liver transplantation for primary sclerosing
      cholangitis is associated with fewer biliary complications in comparison with
      hepaticojejunostomy.
AB  - There is no consensus on the preferred type of biliary reconstruction for
      patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing
      cholangitis (PSC). The aim of this study was to compare long-term outcomes after
      OLT for PSC using either duct-to-duct anastomosis or Roux-en-Y
      hepaticojejunostomy for biliary reconstruction. In a consecutive series of 98
      adult patients undergoing OLT for PSC, 45 underwent duct-to-duct reconstruction,
      and 53 underwent Roux-en-Y biliary reconstruction. The median follow-up was 8.2
      years (interquartile range = 3.9-14.5 years). The outcomes of the 2 groups were
      compared. There were no significant differences in patient demographics or
      general surgical variables between the groups. The overall patient and graft
      survival rates were similar for the 2 groups. The incidence of biliary strictures
      and biliary leakage within the first year after transplantation did not differ
      between the 2 groups. However, significantly more patients in the Roux-en-Y group
      suffered at least 1 episode of cholangitis within the first year (9% in the duct
      to-duct group versus 25% in the Roux-en-Y group, P = 0.04). In addition, Roux-en
      Y reconstruction was associated with a significantly higher rate of late-onset
      (>1 year after transplantation) nonanastomotic biliary strictures (NAS) in
      comparison with duct-to-duct reconstruction (24% versus 7% at 5 years and 30%
      versus 7% at 10 years, P = 0.01). In conclusion, duct-to-duct biliary
      reconstruction in patients with PSC is associated with lower rates of
      posttransplant cholangitis and late-onset NAS in comparison with Roux-en-Y
      hepaticojejunostomy. If technically and anatomically feasible, duct-to-duct
      anastomosis can be performed safely in patients undergoing OLT for PSC.

PMID- 24458731
TI  - Oropharyngeal dysphagia in myotonic dystrophy type 1: a systematic review.
AB  - A systematic review was conducted to investigate the pathophysiology of and
      diagnostic procedures for oropharyngeal dysphagia in myotonic dystrophy (MD). The
      electronic databases Embase, PubMed, and The Cochrane Library were used. The
      search was limited to English, Dutch, French, German, Spanish, and Portuguese
      publications. Sixteen studies met the inclusion criteria. Two independent
      reviewers assessed the methodological quality of the included articles.
      Swallowing assessment tools, the corresponding protocols, the studies' outcome
      measurements, and main findings are summarized and presented. The body of
      literature on pathophysiology of swallowing in dysphagic patients with MD type 1
      remains scant. The included studies are heterogeneous with respect to design and
      outcome measures and hence are not directly comparable. More importantly, most
      studies had methodological problems. These are discussed in detail and
      recommendations for further research on diagnostic examinations for swallowing
      disorders in patients with MD type 1 are provided. 

PMID- 24458732
TI  - The magnificent seven.
AB  - Seven seems to be the number of choice for ChemSusChem in 2014: we're starting
      our seventh year of publication, with a journal impact factor of 7.475, and in
      addition the ChemPubSoc Europe/Wiley-VCH publishing programme welcomes the
      seventh journal in the highly successful ChemXChem series: ChemElectroChem. This
      Editorial discusses what's in store for the coming year: apps, open access,
      Anywhere Article, and many other developments within and around the journal. 

PMID- 24458735
TI  - Schottky or Ohmic metal-semiconductor contact: influence on photocatalytic
      efficiency of Ag/ZnO and Pt/ZnO model systems.
AB  - The relationship between the contact type in metal-semiconductor junctions and
      their photocatalytic efficiencies is investigated. Two metal-semiconductor
      junctions, silver on zinc oxide (Ag/ZnO) and platinum on zinc oxide (Pt/ZnO)
      serve as model system for Ohmic and Schottky metal-semiconductor contact,
      respectively. Ag/ZnO, with Ohmic contact, exhibits a higher photocatalytic
      efficiency than Pt/ZnO, with Schottky contact. The direction of electric fields
      within the semiconductor is found to play a crucial role in the separation of
      photogenerated charges, and thus strongly influences the photocatalytic
      efficiency. 

PMID- 24458736
TI  - Direct alpha-alkylation of ketones with alcohols in water.
AB  - The direct alpha-alkylation of ketones with alcohols has emerged as a new green
      protocol to construct C-C bonds with H2 O as the sole byproduct. In this work, a
      very simple and convenient Pd/C catalytic system for the direct alpha-alkylation
      of ketones with primary alcohols in pure water is developed. Based on this
      catalytic system, aqueous mixtures of dilute acetone, 1-butanol, and ethanol
      (mimicking ABE fermentation products) can be directly transformed into C5 -C11 or
      longer-chain ketones and alcohols, which are precursors to fuels.

PMID- 24458737
TI  - Cholinium-based supported ionic liquid membranes: a sustainable route for carbon
      dioxide separation.
AB  - Aiming at full sustainability of CO2 separation processes, a series of supported
      ionic liquid membranes based on environmentally friendly cholinium carboxylate
      ionic liquids were successfully prepared. Their gas permeation properties were
      measured and high permselectivities were obtained for both CO2 /CH4 and CO2 /N2 .

PMID- 24458738
TI  - Tin oxide microspheres with exposed {101} facets for dye-sensitized solar cells:
      enhanced photocurrent and photovoltage.
AB  - Hierarchical SnO2 microspheres with exposed {101} facets are synthesized by a one
      pot solvothermal reaction and explored as a scattering layer on top of a SnO2
      nanoparticle film for dye-sensitized solar cells (DSCs). The microspheres not
      only enhance photon harvesting by effective light scattering/reflecting but also
      improve the energy level of the conduction band edge of the SnO2 photoanode,
      which leads to a simultaneous increase of the short-circuit photocurrent by 17%
      and open-circuit photovoltage by 20%. An improved overall conversion efficiency
      of 3.46% is achieved for DSCs using the SnO2 microspheres, which is the highest
      value reported so far for pure-SnO2 DSCs. Moreover, the SnO2 -microsphere DSCs
      exhibit a better photostability than the conventional TiO2 DSCs under simulated
      full sunlight.

PMID- 24458739
TI  - Methanol fractionation of softwood Kraft lignin: impact on the lignin properties.
AB  - The development of technologies to tune lignin properties for high-performance
      lignin-based materials is crucial for the utilization of lignin in various
      applications. Here, the effect of methanol (MeOH) fractionation on the molecular
      weight, molecular weight distribution, glass transition temperature (Tg ),
      thermal decomposition, and chemical structure of lignin were investigated.
      Repeated MeOH fractionation of softwood Kraft lignin successfully removed the low
      molecular-weight fraction. The separated high-molecular-weight lignin showed a Tg
      of 211  degrees C and a char yield of 47 %, much higher than those of as-received
      lignin (Tg 153  degrees C, char yield 41 %). The MeOH-soluble fraction of lignin
      showed an increased low-molecular-weight fraction and a lower Tg (117  degrees C)
      and char yield (32%). The amount of low-molecular-weight fraction showed a
      quantitative correlation with both 1/Tg and char yield in a linear regression.
      This study demonstrated the efficient purification or fractionation technology
      for lignin; it also established a theoretical and empirical correlation between
      the physical characteristics of fractionated lignins.

PMID- 24458740
TI  - NAP alpha-aminoisobutyric acid (IsoNAP).
AB  - We set out to identify NAP (davunetide) analogs, providing neuroprotection and
      reducing tau pathology, specifically addressing protection against protein
      misfolding. NAP (NAPVSIPQ, intranasal formulation AL-108) is a drug candidate
      that (1) had a statistically significant impact on two measures, namely digit
      span and delayed-match-to-sample, tests of verbal recall and visual working
      memory, respectively, in patient population of mild cognitive impairment
      [preceding Alzheimer's disease (AD)] and (2) protected functional activities of
      daily living in schizophrenia patients. Previous preclinical studies have shown
      that stabilization of NAP by replacement of all L-amino acids by D-amino acids
      resulted in an active peptide, D-NAP. Other NAP mimetics are now explored. A new
      NAP analog was designed that included replacement of the proline residues by
      alpha-aminoisobutyric acid to enhance beta-sheet breaker characteristics, thereby
      reducing protein misfolding. Three lines of investigations were chosen: (1)
      protection against the AD-associated amyloid beta (1-42), Abeta1-42, peptide
      toxicity in cell cultures; (2) inhibition of AD-associated tau aggregation in
      vitro; and (3) cognitive protection in a mouse model of deficiencies of the NAP
      parent protein, activity-dependent neuroprotective protein (ADNP), exhibiting tau
      pathology and neurodegeneration. NAP alpha-aminoisobutyric acid (IsoNAP)
      protected neurons against AD-associated Abeta1-42-toxicity, inhibited the
      aggregation of the tau-derived peptide VQIVYK (important for the aggregation of
      tau into paired helical filaments, which form the tangles found in AD and related
      disorders), and protected cognitive functions in a model of ADNP deficiency. With
      AD being the major tauopathy, novel NAP derivatives that reduce tauopathy and
      provide neuroprotection as well as cognitive protection are of scientific and
      clinical interest. 

PMID- 24458741
TI  - Localization and chemical coding of the dorsal motor vagal nucleus (DMX) neurons
      projecting to the porcine stomach prepyloric area in the physiological state and
      after stomach partial resection.
AB  - The aim of our study was to localize and define immunocytochemical characteristic
      of the dorsal motor nucleus of the vagus (DMX) neurons projecting to the porcine
      stomach prepyloric region in the physiological state and after gastric partial
      resection. To identify the stomach-projecting perikarya, the neuronal retrograde
      tracer--Fast Blue (FB) was injected into the studied region of control and
      resection group (RES). In the RES group, on 22nd day after FB injection, the
      partial resection of the stomach region previously injected with FB was
      performed. Sections were immunostained with ChAT, pituitary adenylate cyclase
      activating peptide (PACAP), vasoactive intestinal polypeptide (VIP), nitric oxide
      synthase (NOS), galanin (GAL), substance P (SP), leu-enkephalin (LENK), and
      cocaine- and amphetamine-regulated transcript (CART). In the DMX of control and
      RES group, the stomach-projecting perikarya were found in the entire extent of
      the nucleus bilaterally. Within control animals, 30.08 +/- 1.97 % of the gastric
      DMX perikarya expressed PACAP, while other substances were found only in the
      neuronal fibers. In the RES group DMX, PACAP was found in 45.58 +/- 2.2 %, VIP in
      28.83 +/- 3.63 %, NOS in 21.22 +/- 3.32 %, and GAL in 5.67 +/- 1.49 % of the FB
      labeled gastric perikarya. Our data implicate PACAP, VIP, NOS, and GAL as
      neuronal survival promoting substances and the CART-, LENK-, SP- NOS-, and GAL
      immunoreactive processes in control of the gastric vagal neurons in the pig.

PMID- 24458742
TI  - Postnatal dynamics of Zeb2 expression in rat brain: analysis of novel 3' UTR
      sequence reveals a miR-9 interacting site.
AB  - ZEB2 is a transcription factor with established roles in neurogenesis but no
      defined function in postnatal brain despite extensive neuronal expression in
      telencephalic structures. Multiple, incompletely annotated transcripts derive
      from the Zeb2 locus; the purpose of the present study was to structurally
      characterize rat brain Zeb2 transcripts with respect to 3' untranslated (UTR)
      sequence in order to understand Zeb2 transcript regulation including possible
      interactions with regulatory molecules such as neuronal miRNAs. We cloned a 5054
      nucleotide Zeb2 3' UTR that is included in the most abundant Zeb2 transcript in
      neonatal rat brain. Unique features of the distal 3' UTR region included a number
      of brain-specific miRNA target sites; a highly conserved miR-9 target site at 3'
      UTR position 4097 was selected for functional verification in transfection
      experiments. Parallel analysis of Zeb2 transcript, ZEB2 protein and miR-9 levels
      across postnatal brain cortical development revealed a significant accumulation
      of ZEB2 protein levels only between postnatal days P2 and P5 that was associated
      with an acute loss of postnatal miR-9 expression in cortex. These studies
      demonstrate novel features of Zeb2 gene expression in postnatal rat brain and
      highlight the importance of full transcript annotation for identifying the
      complement of potential transcript-interacting regulators. 

PMID- 24458743
TI  - An individual with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES)
      and additional features expands the phenotype associated with mutations in KAT6B.
AB  - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal
      dominant disorder caused by mutations in FOXL2. We identified an individual with
      BPES and additional phenotypic features who did not have a FOXL2 mutation. We
      used whole exome sequencing to identify a de novo mutation in KAT6B (lysine
      acetyltransferase 6B) in this individual. The mutation was a 2-bp insertion
      leading to a frameshift which resulted in a premature stop codon. The resulting
      truncated protein does not have the C-terminal serine/methionine transcription
      activation domain necessary for interaction with other transcriptional and
      epigenetic regulators. This mutation likely has a dominant-negative or gain-of
      function effect, similar to those observed in other genetic disorders resulting
      from KAT6B mutations, including Say-Barber-Biesecker-Young-Simpson (SBBYSS) and
      genitopatellar syndrome (GTPTS). Thus, our subject's phenotype broadens the
      spectrum of clinical findings associated with mutations in KAT6B. Furthermore,
      our results suggest that individuals with BPES without a FOXL2 mutation should be
      tested for KAT6B mutations. The transcriptional and epigenetic regulation
      mediated by KAT6B appears crucial to early developmental processes, which when
      perturbed can lead to a wide spectrum of phenotypic outcomes.

PMID- 24458744
TI  - Role of estrogen on skeletal muscle mitochondrial function in ovariectomized
      rats: a time course study in different fiber types.
AB  - Postmenopausal women are prone to develop obesity and insulin resistance, which
      might be related to skeletal muscle mitochondrial dysfunction. In a rat model of
      ovariectomy (OVX), skeletal muscle mitochondrial function was examined at short-
      and long-term periods after castration. Mitochondrial parameters in the soleus
      and white gastrocnemius muscle fibers were analyzed. Three weeks after surgery,
      there were no differences in coupled mitochondrial respiration (ATP synthesis)
      with pyruvate, malate, and succinate; proton leak respiration; or mitochondrial
      reactive oxygen species production. However, after 3 wk of OVX, the soleus and
      white gastrocnemius muscles of the OVX animals showed a lower use of palmitoyl
      carnitine and glycerol-phosphate substrates, respectively, and decreased
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression.
      Estrogen replacement reverted all of these phenotypes. Eight weeks after OVX, ATP
      synthesis was lower in the soleus and white gastrocnemius muscles of the OVX
      animals than in the sham-operated and estrogen-treated animals; however, when
      normalized by citrate synthase activity, these differences disappeared,
      indicating a lower muscle mitochondria content. No differences were observed in
      the proton leak parameter. Mitochondrial alterations did not impair the treadmill
      exercise capacity of the OVX animals. However, blood lactate levels in the OVX
      animals were higher after the physical test, indicating a compensatory
      extramitochondrial ATP synthesis system, but this phenotype was reverted by
      estrogen replacement. These results suggest early mitochondrial dysfunction
      related to lipid substrate use, which could be associated with the development of
      the overweight phenotype of ovariectomized animals. 

PMID- 24458745
TI  - Acute change of titin at mid-sarcomere remains despite 8 wk of plyometric
      training.
AB  - The purpose of this study was to investigate skeletal muscle changes induced by
      an acute bout of plyometric exercise (PlyEx) both before and after PlyEx
      training, to understand if titin is affected differently after PlyEx training.
      Healthy untrained individuals (N = 11) completed the 1stPlyEx (10 * 10 squat
      jumps, 1-min rest). Thereafter, six subjects completed 8 wk of PlyEx, while five
      controls abstained from any jumping activity. Seven days after the last training
      session, all subjects completed the 2ndPlyEx. Blood samples were collected before
      and 6 h and 1, 2, 3, and 4 days after each acute bout of PlyEx, and muscle
      biopsies 4 days before and 3 days after each acute bout of PlyEx. The 1stPlyEx
      induced an increase in circulating myoglobin concentration. Muscle sample
      analysis revealed Z-disk streaming, a stretch or a fragmentation of titin
      (immunogold), and increased calpain-3 autolysis. After training, 2ndPlyEx did not
      induce Z-disk streaming or calpain-3 activation. The previously observed post
      1stPlyEx positional change of the titin COOH terminus was still present pre
      2ndPlyEx, in all trained and all control subjects. Only two controls presented
      with Z-disk streaming after 2ndPlyEx, while calpain-3 activation was absent in
      all controls. Eccentric explosive exercise induced a stretch or fragmentation of
      titin, which presented as a positional change of the COOH terminus. Calpain-3
      activation does not occur when titin is already stretched before explosive
      jumping. Enzymatic digestion results in titin fragmentation, but since an
      increase in calpain-3 autolysis was visible only after the 1stPlyEx acute bout,
      fragmentation cannot explain the prolonged positional change. 

PMID- 24458746
TI  - The classical Starling resistor model often does not predict inspiratory airflow
      patterns in the human upper airway.
AB  - The upper airway is often modeled as a classical Starling resistor, featuring a
      constant inspiratory airflow, or plateau, over a range of downstream pressures.
      However, airflow tracings from clinical sleep studies often show an initial peak
      before the plateau. To conform to the Starling model, the initial peak must be of
      small magnitude or dismissed as a transient. We developed a method to simulate
      fast or slow inspirations through the human upper airway, to test the hypothesis
      that this initial peak is a transient. Eight subjects [4 obstructive sleep apnea
      (OSA), 4 controls] slept in an "iron lung" and wore a nasal mask connected to a
      continuous/bilevel positive airway pressure machine. Downstream pressure was
      measured using an epiglottic catheter. During non-rapid eye movement (NREM)
      sleep, subjects were hyperventilated to produce a central apnea, then
      extrathoracic pressure was decreased slowly (~2-4 s) or abruptly (<0.5 s) to
      lower downstream pressure and create inspiratory airflow. Pressure-flow curves
      were constructed for flow-limited breaths, and slow vs. fast reductions in
      downstream pressure were compared. All subjects exhibited an initial peak and
      then a decrease in flow with more negative pressures, demonstrating negative
      effort dependence (NED). The rate of change in downstream pressure did not affect
      the peak to plateau airflow ratio: %NED 22 +/- 13% (slow) vs. 20 +/- 5% (fast), P
      = not significant. We conclude that the initial peak in inspiratory airflow is
      not a transient but rather a distinct mechanical property of the upper airway. In
      contrast to the classical Starling resistor model, the upper airway exhibits
      marked NED in some subjects. 

PMID- 24458747
TI  - Influence of divergent exercise contraction mode and whey protein supplementation
      on atrogin-1, MuRF1, and FOXO1/3A in human skeletal muscle.
AB  - Knowledge from human exercise studies on regulators of muscle atrophy is lacking,
      but it is important to understand the underlying mechanisms influencing skeletal
      muscle protein turnover and net protein gain. This study examined the regulation
      of muscle atrophy-related factors, including atrogin-1 and MuRF1, their upstream
      transcription factors FOXO1 and FOXO3A and the atrogin-1 substrate eIF3-f, in
      response to unilateral isolated eccentric (ECC) vs. concentric (CONC) exercise
      and training. Exercise was performed with whey protein hydrolysate (WPH) or
      isocaloric carbohydrate (CHO) supplementation. Twenty-four subjects were divided
      into WPH and CHO groups and completed both single-bout exercise and 12 wk of
      training. Single-bout ECC exercise decreased atrogin-1 and FOXO3A mRNA compared
      with basal and CONC exercise, while MuRF1 mRNA was upregulated compared with
      basal. ECC exercise downregulated FOXO1 and phospho-FOXO1 protein compared with
      basal, and phospho-FOXO3A was downregulated compared with CONC. CONC single-bout
      exercise mediated a greater increase in MuRF1 mRNA and increased FOXO1 mRNA
      compared with basal and ECC. CONC exercise downregulated FOXO1, FOXO3A, and eIF3
      f protein compared with basal. Following training, an increase in basal phospho
      FOXO1 was observed. While WPH supplementation with ECC and CONC training further
      increased muscle hypertrophy, it did not have an additional effect on mRNA or
      protein levels of the targets measured. In conclusion, atrogin-1, MuRF1,
      FOXO1/3A, and eIF3-f mRNA, and protein levels, are differentially regulated by
      exercise contraction mode but not WPH supplementation combined with hypertrophy
      inducing training. This highlights the complexity in understanding the differing
      roles these factors play in healthy muscle adaptation to exercise. 

PMID- 24458748
TI  - Selective skin sensitivity changes and sensory reweighting following short
      duration space flight.
AB  - Skin sensory input from the foot soles is coupled with vestibular input to
      facilitate body orientation in a gravitational environment. Anecdotal
      observations suggest that foot sole skin becomes hypersensitive following space
      flight. The veritable level of skin sensitivity and its impact on postural
      disequilibrium observed post space flight have not been documented. Skin
      sensitivity of astronauts (n = 11) was measured as vibration perception at the
      great toe, fifth metatarsal and heel. Frequencies targeted four classes of
      receptors: 3 and 25 Hz for slow-adapting (SA) receptors and 60 and 250 Hz for
      fast-adapting (FA) receptors. Data were collected pre- and post-space flight. We
      hypothesized that skin sensitivity would increase post-space flight and correlate
      to balance measures. Decreased skin sensitivity was found on landing day at 3 and
      25 Hz on the great toe. Hypersensitivity was found for a subset of astronauts (n
      = 6) with significantly increased sensitivity to 250 Hz at the heel. This subset
      displayed a greater reduction in computerized dynamic posturography (CDP)
      equilibrium (EQ) scores (-54%) on landing vs. non-hypersensitive participants (
      11%). Observed hyposensitivity of SA (pressure) receptors may indicate a strategy
      to reduce pressure input during periods of unloading. Hypersensitivity of FAs
      coupled with reduced EQ scores may reflect targeted sensory reweighting. Altered
      gravito-inertial environments reduce vestibular function in balance control which
      may trigger increased weighting of FAs (that signal foot contact, slips).
      Understanding modulations to skin sensitivity has translational implications for
      mitigating postural disequilibrium following space flight and for on-Earth
      preventative strategies for imbalance in older adults.

PMID- 24458749
TI  - The validity of anthropometric leg muscle volume estimation across a wide
      spectrum: from able-bodied adults to individuals with a spinal cord injury.
AB  - The assessment of muscle volume, and changes over time, have significant clinical
      and research-related implications. Methods to assess muscle volume vary from
      simple and inexpensive to complex and expensive. Therefore this study sought to
      examine the validity of muscle volume estimated simply by anthropometry compared
      with the more complex proton magnetic resonance imaging ((1)H-MRI) across a wide
      spectrum of individuals including those with a spinal cord injury (SCI), a group
      recognized to exhibit significant muscle atrophy. Accordingly, muscle volume of
      the thigh and lower leg of eight subjects with a SCI and eight able-bodied
      subjects (controls) was determined by anthropometry and (1)H-MRI. With either
      method, muscle volumes were significantly lower in the SCI compared with the
      controls (P < 0.05) and, using pooled data from both groups, anthropometric
      measurements of muscle volume were strongly correlated to the values assessed by
      (1)H-MRI in both the thigh (r(2) = 0.89; P < 0.05) and lower leg (r(2) = 0.98; P
      < 0.05). However, the anthropometric approach systematically overestimated muscle
      volume compared with (1)H-MRI in both the thigh (mean bias = 2407cm(3)) and the
      lower (mean bias = 170 cm(3)) leg. Thus with an appropriate correction for this
      systemic overestimation, muscle volume estimated from anthropometric measurements
      is a valid approach and provides acceptable accuracy across a spectrum of adults
      with normal muscle mass to a SCI and severe muscle atrophy. In practical terms
      this study provides the formulas that add validity to the already simple and
      inexpensive anthropometric approach to assess muscle volume in clinical and
      research settings. 

PMID- 24458751
TI  - Resistance exercise training modulates acute gene expression during human
      skeletal muscle hypertrophy.
AB  - We sought to determine whether acute resistance exercise (RE)-induced gene
      expression is modified by RE training. We studied the expression patterns of a
      select group of genes following an acute bout of RE in naive and hypertrophying
      muscle. Thirteen untrained subjects underwent supervised RE training for 12 wk of
      the nondominant arm and performed an acute bout of RE 1 wk after the last bout of
      the training program (training+acute). The dominant arm was either unexercised
      (control) or subjected to the same acute exercise bout as the trained arm (acute
      RE). Following training, men (14.8 +/- 2.8%; P < 0.05) and women (12.6 +/- 2.4%;
      P < 0.05) underwent muscle hypertrophy with increases in dynamic strength in the
      trained arm (48.2 +/- 5.4% and 72.1 +/- 9.1%, respectively; P < 0.01). RE
      training resulted in attenuated anabolic signaling as reflected by a reduction in
      rpS6 phosphorylation following acute RE. Changes in mRNA levels of genes involved
      in hypertrophic growth, protein degradation, angiogenesis, and metabolism
      commonly expressed in both men and women was determined 4 h following acute RE.
      We show that RE training can modify acute RE-induced gene expression in a
      divergent and gene-specific manner even in genes belonging to the same ontology.
      Changes in gene expression following acute RE are multidimensional, and may not
      necessarily reflect the actual adaptive response taking place during the training
      process. Thus RE training can selectively modify the acute response to RE,
      thereby challenging the use of gene expression as a marker of exercise-induced
      adaptations.

PMID- 24458750
TI  - The effect of lifelong exercise dose on cardiovascular function during exercise.
AB  - An increased "dose" of endurance exercise training is associated with a greater
      maximal oxygen uptake (Vo2max), a larger left ventricular (LV) mass, and improved
      heart rate and blood pressure control. However, the effect of lifelong exercise
      dose on metabolic and hemodynamic response during exercise has not been
      previously examined. We performed a cross-sectional study on 101 (69 men) seniors
      (60 yr and older) focusing on lifelong exercise frequency as an index of exercise
      dose. These included 27 who had performed <= 2 exercise sessions/wk (sedentary),
      25 who performed 2-3 sessions/wk (casual), 24 who performed 4-5 sessions/wk
      (committed) and 25 who performed >= 6 sessions/wk plus regular competitions
      (Masters athletes) over at least the last 25 yr. Oxygen uptake and hemodynamics
      [cardiac output, stroke volume (SV)] were collected at rest, two levels of steady
      state submaximal exercise, and maximal exercise. Doppler ultrasound measures of
      LV diastolic filling were assessed at rest and during LV loading (saline
      infusion) to simulate increased LV filling. Body composition, total blood volume,
      and heart rate recovery after maximal exercise were also examined. Vo2max
      increased in a dose-dependent manner (P < 0.05). At maximal exercise, cardiac
      output and SV were largest in committed exercisers and Masters athletes (P <
      0.05), while arteriovenous oxygen difference was greater in all trained groups (P
      < 0.05). At maximal exercise, effective arterial elastance, an index of
      ventricular-arterial coupling, was lower in committed exercisers and Masters
      athletes (P < 0.05). Doppler measures of LV filling were not enhanced at any
      condition, irrespective of lifelong exercise frequency. These data suggest that
      performing four or more weekly endurance exercise sessions over a lifetime
      results in significant gains in Vo2max, SV, and heart rate regulation during
      exercise; however, improved SV regulation during exercise is not coupled with
      favorable effects on LV filling, even when the heart is fully loaded.

PMID- 24458753
TI  - Effects of prepubertal-onset exercise on body weight changes up to middle age in
      rats.
AB  - The present study was conducted to examine whether prepubertal-onset exercise
      might help adults maintain long-term body weight (BW) reduction and increased
      energy metabolism after the cessation of exercise. Furthermore, the effects of
      the exercise regimen were compared with those of food restriction. Twenty-three
      male obese-diabetic [Otsuka Long-Evans Tokushima Fatty (OLETF)] rats were
      randomly assigned to prepubertal-onset exercise (Childhood-Ex), food restriction
      (Childhood-Diet), and sedentary control (OLETF-Sed) groups. Childhood-Ex rats
      exercised voluntarily every day using a rotating wheel, while the food volume of
      the Childhood-Diet group was restricted to achieve a BW similar to that recorded
      in the Childhood-Ex group. Both treatments were conducted at 5-19 wk of age;
      after this period, the rats were kept sedentary and allowed ad libitum food
      intake until 45 wk of age. BW was significantly lower, and percent lean body mass
      was significantly higher, in the Childhood-Ex group compared with those in the
      Childhood-Diet and OLETF-Sed groups throughout maturation and middle age after
      cessation of the interventions. The Childhood-Ex group also demonstrated higher
      citrate synthase, succinate dehydrogenase, and phosphofructokinase activity
      levels, as well as uncoupling protein-3 mRNA expression in skeletal muscle. This
      study revealed that inhibited BW gain in an animal model of human obese diabetes
      by prepubertal-onset exercise lasted for a long period after the completion of
      the exercise intervention. This effect may be facilitated by increased energy
      metabolism. However, these benefits were not found by prepubertal food
      restriction treatment. Importantly, to allow translation of our work, these novel
      insights need to be assessed in obese human individuals.

PMID- 24458752
TI  - The unusual symmetric reopening effect induced by pulmonary surfactant.
AB  - This study investigates the stability of a finger of air as it propagates into a
      liquid-filled model of a liquid-filled model of a pulmonary bifurcation. We seek
      to elucidate the stability characteristics of the reopening of daughter airways,
      an event that may be important to the treatment of acute lung disease. To do so,
      we investigated the symmetry of reopening under conditions of nearly constant
      surface tension with 1) purified H2O or 2) an anionic surfactant (sodium dodecyl
      sulfate). Dynamic surface tension was investigated using pulmonary surfactant
      (Infasurf) with and without the presence of albumin. Flow visualization was
      accomplished using a microparticle image velocimetry (MU-PIV)/shadowgraph system
      through which we measured 1) the propagation velocity of the finger of air that
      reopens each daughter branch, and 2) the instantaneous and averaged velocity
      field of liquid phase surrounding the tip of the propagating bubble. Only
      pulmonary surfactant demonstrated the ability of maintaining a nearly symmetric
      propagation in the daughter channels, which is likely to lead to homogeneous
      airway reopening. In contrast, when pulmonary surfactant was inactivated by
      albumin or when the system was held at a nearly constant surface tension,
      reopening occurred asymmetrically. Our analysis suggests that Infasurf's dynamic
      surface tension qualities are important to stabilize the removal of liquid
      obstructions. This demonstrates a new important function of pulmonary surfactant
      for airway reopening of a multibranched network.

PMID- 24458755
TI  - Regulators of cell division in plant tissues. XVI : Metabolism of zeatin by
      radish cotyledons and hypocotyls.
AB  - [(3)H]Zeatin was supplied through the transpiration stream to radish (Raphanus
      sativus L.) seedlings with roots excised. Formation of dihydrozeatin was not
      detected but numerous other metabolites were formed, including adenine,
      adenosine, AMP, zeatin riboside and zeatin riboside-5'-monophosphate. However, in
      labelled seedlings which had been left in water for 15 h, an unknown compound
      (raphanatin) was the dominant metabolite and accounted for about 25% of the total
      radioactivity extracted. A procedure for the isolation of this metabolite was
      devised and yielded 70 MUg from 1600 seedlings. Raphanatin was characterized by
      mass and ultraviolet spectra and has been identified as 7-glucosylzeatin. It is
      an active and very stable metabolite which was located mainly in the cotyledon
      laminae and may be a storage form of the hormone. In contrast, labelled
      nucleotides, the other major metabolites of zeatin, were largely confined to the
      hypocotyls and petioles. Zeatin riboside-5'-monophosphate was the dominant
      metabolite in hypocotyls of de-rooted seedlings supplied with zeatin for 0.5-2 h.
      The majority of the radioactivity in the xylem sap was due to zeatin, but about
      10% was present as zeatin riboside; nucleotides accounted for less than 10% of
      the radioactivity and labelled raphanatin was not detected. 

PMID- 24458754
TI  - WISE-2005: Countermeasures to prevent muscle deconditioning during bed rest in
      women.
AB  - The objectives of this study were to evaluate the efficacy of two separate
      countermeasures, exercise and protein supplementation, to prevent muscle strength
      and lean tissue mass losses during 60 days of bed rest (BR) in women and whether
      countermeasure efficacy was influenced by pre-BR muscular fitness (strength,
      endurance, tissue mass). Twenty-four women were assigned to an exercise (EX, n =
      8), a no-exercise control (CON, n = 8), or a no-exercise protein supplementation
      group (PROT, n = 8). EX performed supine treadmill exercise within lower body
      negative pressure 3-4 days/wk and maximal concentric and eccentric supine leg-
      and calf-press exercises 2-4 days/wk. PROT consumed a diet with elevated protein
      content compared with CON and EX (1.6 vs. 1.0 g.kg(-1).day(-1)). Knee and calf
      isokinetic strength and endurance, isotonic leg-press strength, and leg lean mass
      were measured before and after BR. Post-BR knee extensor strength and endurance,
      ankle strength, and leg lean mass were significantly greater and leg-press
      strength tended to be higher in EX than in CON and PROT. Post-BR measures in PROT
      were not different than those in CON. Exercise countermeasure efficacy was less,
      and strength, endurance, and leg lean mass losses in CON and PROT were greater,
      in subjects who were more fit pre-BR. An exercise protocol combining resistive
      and aerobic exercise training protects against losses in strength, endurance, and
      leg lean mass in women during BR, while a nutritional countermeasure without
      exercise was not effective. Exercise countermeasures may require
      individualization to protect higher levels of strength and endurance.

PMID- 24458756
TI  - Some enzyme activities associated with the chlorophyll containing layers of the
      immature barley pericarp.
AB  - Some photosynthetic and biochemical properties of the chlorophyl containing
      layers of the pericarp of developing barley have been investigated. The tissue
      changes from pale green to bright green early in development, chlorophyll
      disappearing only at the later stages of maturity. It contains chloroplasts and
      probably amyloplasts and starch bearing chloroplasts. It is capable of high rates
      of light dependent oxygen evolution. It has been shown that the enzyme
      phosphoenol pyruvate carboxylase (EC 4.1.1.31) is present in the pericarp and is
      100 times as active in carbon dioxide fixation as ribulose diphosphate
      carboxylase (EC 4.1.1.39). Other enzymes present in the pericarp are phosphoenol
      pyruvate synthetase, pyrophosphatase (EC 3.6.1.1), malate NAD and NADP
      dehydrogenases (EC 1.1.1.37), malic enzyme (EC 1.1.1.40), and fructose 1,6
      diphosphatase (EC 3.1.3.11). 

PMID- 24458757
TI  - Non-coordinate synthesis and methylation of tRNA following excision of plant
      tissue.
AB  - The relationship between the synthesis and methylation of nucleic acids in tissue
      slices from higher plant storage organs has been investigated. Although the
      observed nucleic acid synthesis is mainly an expression of rRNA synthesis the
      highest level of methylation occurs in tRNA. Unlike the synthesis and methylation
      of rRNA which appears completely coupled, the methylation of tRNA is not tightly
      coupled to its synthesis. It is suggested that a pool of undermethylated tRNA
      exists in the tissue prior to incubation and that methylation of this tRNA
      initially controls the rate of protein synthesis in the tissue slices. 

PMID- 24458758
TI  - [Studies on the ultrastructure of the nucleus of Acetabularia by the freeze
      etching technique].
AB  - The ultrastructure of the "primary" nucleus of the marine green algae
      Acetabularia (Polyphysa) cliftonii as revealed by the freeze-etching technique is
      described.The nuclear envelope is perforated by about 3*10(6) pores which appear
      arranged nearly in rows. The nucleus is covered with a layer of cytoplasm which
      protects it in the isolated state and resists various manipulations. This
      cytoplasmic layer is protected by an elementary membrane. The latter appears
      rough on the cytoplasmic side, and smooth on the side facing the "cell sap". The
      cytoplasmic layer and the surrounding perinuclear cytoplasm are connected by
      cytoplasmic ducts. The nucleus appears irregularly shaped owing to many
      invaginations in the nuclear envelope. Sometimes mitochondria are observed in
      these cavities. 

PMID- 24458759
TI  - K(+)-dependent net Na(+) efflux in roots of barley plants.
AB  - The influence of K(+) ions on the net Na(+) fluxes in cells of excised barley
      roots (Hordeum distichon L.) and roots of whole barley plants was investigated.
      The fluxes were determined by flame photometry in the external solution. In both
      cases a transient net Na(+) efflux against the external Na(+) concentration was
      observed upon addition of K(+). The results stress the effectiveness of the K(+)
      dependent Na(+) efflux mechanism residing at the plasmalemma, and its involvement
      in K-Na-selectivity in whole barley plants. 

PMID- 24458760
TI  - [Studies on some phenolic compounds in Matthiola incana].
AB  - 1-Sinapoylglucose was isolated in cristalline form from mutants of Matthiola
      incana. In addition, 1-feruloyl-glucose and 1-p-cumaroyl-glucose were isolated
      and identified by paper chromatography. The molecular weights of penta
      (trimethylsilyl)-1-sinapoyl-glucose and penta-(trimethylsilyl)-1-feruloyl-glucose
      have been determined by mass-spectroscopy.Two additionally isolated flavonol
      glycosides from Matthiola incana have been found to be kaempferol-7-rhamnoside-3
      (rhamnosylarabinoside) and kaempferol-7-rhamnoside-3-(rhamnosylglucoside). 

PMID- 24458761
TI  - [Synthesis of chlorophyll and of chloroplast structure in Chlorella without
      participation of chloroplast ribosomes].
AB  - The unicellular green alga Chlorella pyrenoidosa shows normal heterotrophic
      growth and pigment synthesis in the presence of inhibitors of chloroplast
      transcription and translation.Cells treated with 100 MUg/ml of rifampin, 25
      MUg/ml of lincomycin or 25 MUg/ml of spectinomycin for 48 h do not contain any
      chloroplast ribosomes, 16 S or 23 S RNA as shown with cell fractionation and gel
      electrophoresis. Labeling experiments with [5(-3) H]uridine indicate that
      rifampin blocks completely the formation of 16 S and 23 S RNA whilst cytoplasmic
      rRNA synthesis is unaffected.Production of dry matter and of cell nitrogen are
      unaffected by treatment of the cells with antibiotics. Chlorophyll production is
      almost normal as compared with the untreated control culture. The release of
      daughter cells is partially inhibited by rifampin treatment. In such cultures,
      giant cells can be observed among cells of normal size.The O2-production of
      rifampin-treated cells remains unaffected up to 24 h after application of the
      drug. Later on, the oxygen evolution declines and, after 72 h, oxygen is consumed
      even during illumination. The O2-consumption in the dark is markedly enhanced
      after rifampin treatment.Electron microscopy of rifampin-treated Chlorella shows
      that apparently normal chloroplast membranes are formed. The thylakoids are
      arranged in grana-like structures whereas in untreated cells they form only
      stacks of two or three thylakoids. In the chloroplasts of rifampin-treated
      Chlorella cells, no more ribosomes are found.The cellular location of synthesis
      of some chloroplast constituents is discussed. 

PMID- 24458762
TI  - Gibberellin A20 content of Bryophyllum daigremontianum under different
      photoperiodic conditions as determined by gas-liquid chromatography.
AB  - The gibberellin A20 content of the long-short-day plant Bryophyllum
      daigremontianum (R. Hamet and Perr.) Berg. under different photoperiodic
      conditions was determined by gas-liquid chromatography. Purified extracts from
      ten plants were adequate for quantitative analysis by this method. The level of
      GA20 increased following transfer from long-day (LD) to short-day (SD) conditions
      until after 38 SD it was three times higher on a dry weight basis than in
      comparable plants under continuous LD. No GA20 could be detected in extracts of
      plants under permanent SD. These results are in agreement with earlier data
      obtained by assaying Bryophyllum extracts with the d-5 mutant of corn. 

PMID- 24458763
TI  - Fairly rare de novo inflammatory pseudotumor in a graft after living donor liver
      transplantation.

PMID- 24458764
TI  - Characterization and proteome analysis of inosine 5-monophosphate dehydrogenase
      in epidemic Streptococcus suis serotype 2.
AB  - Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes
      severe disease symptoms in pigs and humans. In the present study, we found one
      isogenic mutant lacking inosine 5-monophosphate dehydrogenase (IMPDH)
      DeltaZY05719 was attenuated in pigs compared with the wild-type SS2 strain
      ZY05719. Comparative proteome analysis of the secreted proteins expression
      profiles between ZY05719 and DeltaZY05719 allowed us to identify Triosephosphate
      isomerase (TPI) and glyceraldehyde phosphate dehydrogenase (GAPDH), which were
      down expressed in the absence of the IMPDH. Both of them are glycolytic enzymes
      participating in the glycolytic pathway. Compared with ZY05719, DeltaZY05719 lost
      the ability of utilize mannose, which might relate to down expression of TPI and
      GAPDH. In addition, GAPDH is a well-known factor that involved in adhesion to
      host cells, and we demonstrated ability of adhesion to HEp-2 and PK15 by
      DeltaZY05719 was significantly weakened, in contrast to ZY05719. The adhesion to
      host cells is the crucial step to cause infection for pathogen, and the reduction
      adhesion of DeltaZY05719, to some extent illustrates the attenuated virulence of
      DeltaZY05719.

PMID- 24458766
TI  - Microvasculature of the cerebral cortex: a vascular corrosion cast and
      immunocytochemical study.
AB  - In mammals, the cerebral cortex microvasculature (CCM) of the neopallium plays
      important roles in the physiological and pathological processes of the brain. The
      aim of the present work is to analyze the CCM by use of the SEM-vascular
      corrosion cast technique, and to examine the immunocytochemical characteristics
      of the CCM in adult domestic ruminants (cattle, buffalo, and sheep) by using the
      SEM-immunogold technique. The CCM originated from the very small, finger-like
      terminal branches of the macrovasculature of the brain. The superficial cortical
      arterioles were more numerous than the deep straight arterioles which proceeded
      toward the white matter. The surface casts of the arterioles and capillaries of
      the cerebral cortex showed ring-shaped formations in the arterioles and at the
      origin of the capillaries. All capillaries down-stream from these ring-shaped
      formations were flaccid. Casts of the capillaries showed wrinkles due to the
      presence of endothelial folds, which is characteristic of varying blood pressure.
      Formations having intense anti-GIFAP immunoreactivity were frequently evident
      along the course of the blood capillaries in the cerebral cortex. These
      formations were probably astrocytes that might regulate the cerebral
      microcirculation based on physiological and pathological stimuli, such as
      neuronal activation.

PMID- 24458765
TI  - Exposure to violence predicting cortisol response during adolescence and early
      adulthood: understanding moderating factors.
AB  - Previous research on the association between violence and biological stress
      regulation has been largely cross-sectional, and has also focused on childhood.
      Using longitudinal data from a low-income, high-risk, predominantly African
      American sample (n = 266; 57 % female), we tested hypotheses about the influence
      of cumulative exposure to violence during adolescence and early adulthood on
      cortisol responses in early adulthood. We found that cumulative exposure to
      violence predicted an attenuated cortisol response. Further, we tested whether
      sex, mothers' support, or fathers' support moderated the effect of exposure to
      violence on cortisol responses. We found that the effect of cumulative exposure
      to violence on cortisol was modified by sex; specifically, males exposed to
      violence exhibited a more attenuated response pattern. In addition, the effect of
      cumulative exposure to violence on cortisol was moderated by the presence of
      fathers' support during adolescence. The findings contribute to a better
      understanding of how cumulative exposure to violence influences biological
      outcomes, emphasizing the need to understand sex and parental support as
      moderators of risk. 

PMID- 24458767
TI  - Monochorionic twins discordant for mosaic trisomy 14.
AB  - Monochorionic-diamniotic twins are usually monozygotic twins and known to be
      associated with adverse obstetric and perinatal outcomes. Cases of discordant
      karyotype of monozygotic twins are rare and most involves sex chromosomes. We
      present the first case of monochorionic twins with discordant karyotype
      manifested as mosaic trisomy 14 in one twin (B) and a normal karyotype in the
      other (A). We describe the postmortem pathological and imaging findings of the
      trisomic twin and for the first time neuropathological findings of this entity.
      Metaphase chromosome analysis of twin B using fetal tissue showed a 47,XX, +14
      karyotype. Chromosomal microarray analysis (CMA) using fetal tissue revealed 38%
      mosaicism. CMA with placental tissue from both sides demonstrated normal
      karyotype and confirmed monozygosity, highlighting the value of array based
      testing on diagnosing mosaicism and zygosity.

PMID- 24458768
TI  - The catalytic pathways of hydrohalogenation over metal-free nitrogen-doped carbon
      nanotubes.
AB  - Nitrogen-doped carbon nanotubes (N-CNTs) are found to be active as one novel
      heterogeneous catalyst for acetylene hydrochlorination reaction, possessing good
      activity (TOF=2.3*10(-3)  s(-1) ) and high selectivity (>98 %). Compared to toxic
      and energy-consuming conventional catalysts, such as HgCl2 , N-CNTs are more
      favorable in terms of sustainability, because of their thermo-stability, metal
      free make up, and the wide availability of bulk CNT. Coupling X-ray photoelectron
      spectroscopy and density functional theory computations (DFT), the main active
      source and reaction pathway are shown. Good linearity between the quaternary
      nitrogen content and conversion is revealed. DFT study shows that the nitrogen
      doping enhanced the formation of the covalent bond between C2 H2 and NCNT
      compared with the undoped CNT, and therefore promoted the addition reaction of
      the C2 H2 and HCl into C2 H3 Cl.

PMID- 24458769
TI  - The importance of climatic factors and outliers in predicting regional monthly
      campylobacteriosis risk in Georgia, USA.
AB  - Incidence of Campylobacter infection exhibits a strong seasonal component and
      regional variations in temperate climate zones. Forecasting the risk of infection
      regionally may provide clues to identify sources of transmission affected by
      temperature and precipitation. The objectives of this study were to (1) assess
      temporal patterns and differences in campylobacteriosis risk among nine climatic
      divisions of Georgia, USA, (2) compare univariate forecasting models that analyze
      campylobacteriosis risk over time with those that incorporate temperature and/or
      precipitation, and (3) investigate alternatives to supposedly random walk series
      and non-random occurrences that could be outliers. Temporal patterns of
      campylobacteriosis risk in Georgia were visually and statistically assessed.
      Univariate and multivariable forecasting models were used to predict the risk of
      campylobacteriosis and the coefficient of determination (R(2)) was used for
      evaluating training (1999-2007) and holdout (2008) samples. Statistical control
      charting and rolling holdout periods were investigated to better understand the
      effect of outliers and improve forecasts. State and division level
      campylobacteriosis risk exhibited seasonal patterns with peaks occurring between
      June and August, and there were significant associations between
      campylobacteriosis risk, precipitation, and temperature. State and combined
      division forecasts were better than divisions alone, and models that included
      climate variables were comparable to univariate models. While rolling holdout
      techniques did not improve predictive ability, control charting identified high
      risk time periods that require further investigation. These findings are
      important in (1) determining how climatic factors affect environmental sources
      and reservoirs of Campylobacter spp. and (2) identifying regional spikes in the
      risk of human Campylobacter infection and their underlying causes.

PMID- 24458771
TI  - Nuclear pea mutants deficient in chlorophyll b and the major polypeptide of the
      light-harvesting chlorophyll a/b protein of photosystem II.
AB  - Eight chlorophyll b deficient nuclear mutants of pea (Pisum sativum L.) have been
      characterized by low temperature fluorescence emission spectra of their leaves
      and by the ultrastructure, photochemical activities and polypeptide compositions
      of the thylakoid membranes. The room temperature fluorescence induction kinetics
      of leaves and isolated thylakoids have also been recorded. In addition, the
      effects of Mg(2+) on the fluorescence kinetics of the membranes have been
      investigated. The mutants are all deficient in the major polypeptide of the light
      harvesting chlorophyll a/b protein of photosystem II. The low temperature
      fluorescence emission spectra of aurea-5106, xantha-5371 and -5820 show little or
      no fluorescence around 730 nm (photosystem I fluorescence), but possess maxima at
      685 and 695 nm (photosystem II fluorescence). These three mutants have low
      photosystem II activities, but significant photosystem I activities. The long
      wavelength fluorescence maximum is reduced for three other mutants. The Mg(2+)
      effect on the variable component of the room temperature fluorescence (685 nm)
      induction kinetics is reduced in all mutants, and completely absent in aurea-5106
      and xantha-5820. The thylakoid membranes of these 2 mutants are appressed
      pairwise in 2-disc grana of large diameter. Chlorotica-1-206A and-130A have
      significant long-wavelength maxima in the fluorescence spectra and show the
      largest Mg(2+) enhancement of the variable part of the fluorescence kinetics.
      These two mutants have rather normally structured chloroplast membranes, though
      the stroma regions are reduced. The four remaining mutants are in several
      respects of an intermediate type. 

PMID- 24458770
TI  - Standardized phenology monitoring methods to track plant and animal activity for
      science and resource management applications.
AB  - Phenology offers critical insights into the responses of species to climate
      change; shifts in species' phenologies can result in disruptions to the ecosystem
      processes and services upon which human livelihood depends. To better detect such
      shifts, scientists need long-term phenological records covering many taxa and
      across a broad geographic distribution. To date, phenological observation efforts
      across the USA have been geographically limited and have used different methods,
      making comparisons across sites and species difficult. To facilitate coordinated
      cross-site, cross-species, and geographically extensive phenological monitoring
      across the nation, the USA National Phenology Network has developed in situ
      monitoring protocols standardized across taxonomic groups and ecosystem types for
      terrestrial, freshwater, and marine plant and animal taxa. The protocols include
      elements that allow enhanced detection and description of phenological responses,
      including assessment of phenological "status", or the ability to track presence
      absence of a particular phenophase, as well as standards for documenting the
      degree to which phenological activity is expressed in terms of intensity or
      abundance. Data collected by this method can be integrated with historical
      phenology data sets, enabling the development of databases for spatial and
      temporal assessment of changes in status and trends of disparate organisms. To
      build a common, spatially, and temporally extensive multi-taxa phenological data
      set available for a variety of research and science applications, we encourage
      scientists, resources managers, and others conducting ecological monitoring or
      research to consider utilization of these standardized protocols for tracking the
      seasonal activity of plants and animals. 

PMID- 24458772
TI  - New methods for making chloroplast lipid liposomes and for reconstituting
      chlorophyll-protein complexes isolated from SDS polyacrylamide gels.

PMID- 24458773
TI  - Photoacoustic study of the green alga Trebouxia in the lichen Ramalina duriaei in
      vivo.
AB  - Photosynthetic parameters of the lichen Ramalina duriael were investigated in
      vivo, by the photoacoustic method using intensity-modulated exciting light
      (frequency range 5-300 Hz). The photoacoustic signal in intact lichens was
      similar in its general characteristics to that obtained from intact leaves of
      higher plants (Poulet et al., Biochim. Biophys. Acta 724, 433-446, 1983). It
      included two components interpreted to be due to modulated heat and modulated
      oxygen evolution. The quantum yield of the oxygen evolution component was maximal
      in the red spectral region and exhibited the 'red drop' decrease at wavelengths
      larger than 680 nm, similar to observations in higher plants. In contrast to
      those however, there was a pronounced decrease in this yield in the region below
      about 600 nm, indicating that pigments absorbing at shorter wavelengths are
      inefficient energy transfer agents. Similar results were observed for the quantum
      yield spectrum of photochemical energy storage. Analysis of oxygen diffusion in
      the symbiont alga, from the modulation frequency dependence of the ratio of
      oxygen evolution to photothermal signal component is consistent with an average
      diffusion path of about 4 MUm, compared to a smaller, 1 MUm, average diffusion
      path obtained in green leaves. 

PMID- 24458774
TI  - Photosynthetic/photorespiratory characteristics of C3-C 4 intermediate species.
AB  - The extent of photorespiration, the inhibition of apparent photosynthesis (APS)
      by 21% O2, and the leaf anatomical and ultrastructural features of the naturally
      occurring C3-C4 intermediate species in the diverse Panicum, Moricandia, and
      Flaveria genera are between those features of representative C3 and C4 plants.
      The greatest differences between the photosynthetic/photorespiratory CO2 exchange
      characteristics of the C3-C4 intermediates and C3 plants occur for the parameters
      which are measured at low pCO2 (i.e., the CO2 compensation concentration and
      rates of CO2 evolution into CO2-free air in the light). The rates of APS by the
      intermediate species at atmospheric pCO2 are similar to those of C3 plants.The
      mechanisms which are responsible for reducing photorespiration in the C3-C4
      intermediate species are poorly understood, but two proposals have been advanced.
      One emphasizes the importance of limited C4 photosynthesis which reduces O2
      fixation by ribulose 1,5-bisphosphate carboxylase/oxygenase, and, thus, reduces
      photorespiration by a CO2-concentrating mechanism, while the other emphasizes the
      importance of the internal recycling of photorespiratory CO2 evolved from the
      chloroplast/mitochondrion-containing bundle-sheath cells. There is no evidence
      from recent studies that limited C4 photosynthesis is responsible for reducing
      photorespiration in the intermediate Panicum and Moricandia species. However,
      preliminary results suggest that some, but not all, of the intermediate Flaveria
      species may possess a limited C4 cycle. The importance of a chlorophyllous bundle
      sheath layer in the leaves of intermediate Panicum and Moricandia species in a
      mechanism based on the recycling of photorespiratory CO2 is uncertain.Therefore,
      although they have yet to be clearly delineated, different strategies appear to
      exist in the C3-C4 intermediate group to reduce photorespiration. Of major
      importance is the finding that some mechanism(s) other than Crassulacean acid
      metabolism or C4 photosynthesis has (have) evolved in at least the majority of
      these terrestrial intermediate species to reduce the seemingly wasteful metabolic
      process of photorespiration. 

PMID- 24458775
TI  - Shade adaptation of photosynthesis in Coffea arabica.
AB  - The effect of irradiance on the rate of net photosynthesis was measured for
      mature leaves of coffee grown under five levels of radiation from 100% to 5%
      daylight. The rate of light-saturated photosynthesis per unit leaf area (PNmax)
      increased from 2 MUmol CO2 m(-2) s(-1) under 5% daylight to 4.4 MUmol CO2 m(-2)
      s(-1) under 100% daylight. The photon flux density (PAR, photosynthetically
      active radiation) needed for 50% saturation of photosynthesis, as well as the
      light compensation point, also increased with increasing levels of irradiation
      during growth. The quantum efficiency of photosynthesis (alpha), measured by the
      initial slope of the photosynthetic response to increasing irradiance, was
      greater under shaded growth conditions. The rate of dark respiration was greatest
      for plants grown in full daylight. On the basis of the increase in the quantal
      efficiency of photosynthesis and the low light compensation point when grown
      under shaded conditions, coffee shows high shade adaptation. Plants adjusted to
      shade by an increased ability to utilize short-term increases in irradiance above
      the level of the growth irradiance (measured by the difference between
      photosynthesis at the growth irradiance, PNg, and PNmax). 

PMID- 24458776
TI  - Efficiency of hydrogen photoproduction by photosystem I-enriched subchloroplast
      vesicles combined with Proteus mirabilis cells. Effects of some exogenous
      electron donors.
AB  - High rates of hydrogen photoproduction are obtained when glutaraldehyde-fixed
      Photosystem I-enriched vesicles (Photosystem II-depleted) are added to
      hydrogenase-containing cells of Proteus mirabilis in the presence of the mediator
      methylviologen and a suitable electron donating system. This donor system
      includes ascorbate, dithioerythritol (DTE) and the mediator tetramethylphenylene
      diamine (TMPD) and reduces the photosynthetic electron transfer chain at the
      level of plastocyanin. Both DTE and ascorbate are required for hydrogen
      photoproduction, DTE being the ultimate electron donor and ascorbate only having
      a catalytic function. Whereas the aerobic photoreduction of methylviologen is
      similar in the presence of DTE, ascorbate or both, under anaerobic conditions
      only combination of both compounds results in a high and stable amount of reduced
      methylviologen that can be utilized by the hydrogenase. It is concluded that
      oxidation reactions of reduced methylviologen, competing with the hydrogenase,
      rather than methylviologen photoreduction, limit hydrogen photoproduction in the
      presence of either DTE or ascorbate. These oxidation reactions are suggested to
      involve back reactions to the oxidized form(s) of ascorbate and DTE but backflow
      to the photosynthetic electron transfer chain (i.e. cyclic electron transfer) can
      not be excluded. 

PMID- 24458777
TI  - Temperature dependent changes in absorption and fluorescence properties of the
      cyanobacterium Anacystis nidulans.
AB  - Temperature dependent changes in absorbance and fluorescence of chlorophyll a
      (Chl a) were analyzed in membrane fragments and in a Chl-protein complex
      reconstituted with lipids isolated from the cyanobacterium Anacystis nidulans.
      Absorbance versus temperature curves measured at 656 nm showed an inflection
      point at 23-24 degrees C and at 14-16 degrees C in the membrane fragments
      prepared from A. nidulans cells, grown at 39 degrees  and 25 degrees C,
      respectively. Temperature-induced absorbance changes measured at 680 and 696 nm
      did not show clear break points. The presence of lipids was essential in order to
      see a clear maximum in the fluorescence versus temperature curve of Chl a in a
      Chl-protein complex. It is suggested that a specific form of Chl a may be
      associated with lipids in the thylakoid membranes and that this form of Chl a may
      be responsible for temperature-induced absorbance and fluorescence yield changes
      in this cyanobacterium. 

PMID- 24458778
TI  - An investigation into the interaction between nitrogen nutrition, photosynthesis
      and photorespiration.
AB  - Photosynthetic CO2 assimilation, photorespiration and levels of glycollate
      oxidase and ribulose bisphosphate (RuBP) carboxylase were measured in barley,
      wheat and maize plants grown on media containing nitrate or ammonium or in plants
      transferred from nitrate to ammonium. The CO2 compensation point and
      photorespiratory CO2 release were not altered by the nitrogen growth regime nor
      by transfer from nitrate to ammonium. In barley and wheat plants grown on
      ammonium the levels of glycollate oxidase and RuBP carboxylase per unit leaf area
      were higher than in nitrate grown material. These differences were not evident
      when the results were expressed on a protein or chlorophyll basis. The ratio of
      glycollate oxidase activity to RuBP carboxylase activity was not altered by the
      nitrogen regime. 

PMID- 24458779
TI  - Correction.

PMID- 24458780
TI  - Paper microfluidics goes digital.
AB  - The first example of so-called "digital microfluidics" (DMF) implemented on paper
      by inkjet printing is reported. A sandwich enzyme-linked immunosorbent assay
      (ELISA) is demonstrated as an example of a complex, multistep protocol that would
      be difficult to achieve with capillary-driven paper microfluidics. Furthermore,
      it is shown that paper-based DMF devices have comparable performance to
      traditional photolithographically patterned DMF devices at a fraction of the
      cost. 

PMID- 24458781
TI  - Impact of comorbidities by ACE-27 in the revised-IPSS for patients with
      myelodysplastic syndromes.
AB  - Comorbidities significantly affect the prognosis and outcomes of patients with
      hematological malignancies. We have previously reported the impact of
      comorbidities on the International Prognostic Scoring System (IPSS) score. The
      aim of this study was to determine whether comorbidities continued to have a
      significant impact when patients were reclassified according to the Revised-IPSS
      (IPSS-R). The medical records of 600 consecutive myelodysplastic syndrome
      patients who presented to MD Anderson Cancer Center between January 2002 and June
      2004 were reviewed. The Adult Comorbidity Evaluation-27 (ACE-27) was used to
      assess the severity of comorbid conditions. Four hundred and two (67%) patients
      were male. Median age at presentation was 66.6 years (17-94). Mean duration of
      follow-up was 54 months (1-100). Five hundred and two (84%) patients died, and 54
      (9%) patients underwent stem cell transplantation. Overall median survival was
      16.8 months (1-100). Median survival by IPSS-R was 47, 34, 21, 16, and 6 months
      for patients in very low, low, intermediate, high, and very high-risk groups,
      respectively (P < 0.001). The ACE-27 comorbidity score significantly impacted the
      median survival of patients in the intermediate (P < 0.001), high (P = 0.045),
      and very high (P = 0.004) IPSS-R groups; but did not significantly impact the
      median survival in the low (P = 0.11) and very low (P = 0.49) IPSS-R groups. The
      ACE-27 comorbidity score significantly impacted the median survival of patients
      <=65 years (P < 0.001) but did not significantly impact those >65 years (P =
      0.18). Assessment of comorbidity may enhance the prognostic ability of the IPSS
      R.

PMID- 24458782
TI  - Association between alcohol use and HIV-related sexual risk behaviors among men
      who have sex with men (MSM): findings from a multi-site bio-behavioral survey in
      India.
AB  - This paper examines the association between alcohol use and HIV-related sexual
      risk behaviors among men who have sex with men (MSM). A cross-sectional bio
      behavioral survey was conducted among 3,880 MSM, recruited using time-location
      cluster sampling from cruising sites in three Indian states. Nearly three-fifths
      of the participants reported alcohol use. Among frequent users (40 % of the
      sample), defined as those who consumed alcohol daily or at least once a week, 66
      % were aged 25 years and above, 53 % self-identified as kothi
      (feminine/receptive), and 63 % consistently used condoms with male paying
      partners. Multivariate logistic regression demonstrated that frequent users were
      more likely to be aged 25 years and above, less likely to self-identify as kothi,
      and less likely to consistently use condoms with male paying (AOR = 0.7; 95 % CI
      0.5-0.9) and male regular (AOR = 0.7; 95 % CI 0.6-0.9) partners. HIV prevention
      interventions for MSM need to provide tailored information on alcohol use-related
      sexual risk, especially for MSM in sex work and MSM with male regular partners.

PMID- 24458783
TI  - Mesenchymal stem cell and gelatin microparticle encapsulation in thermally and
      chemically gelling injectable hydrogels for tissue engineering.
AB  - In this work, we investigated the viability and osteogenic differentiation of
      mesenchymal stem cells encapsulated with gelatin microparticles (GMPs) in an
      injectable, chemically and thermally gelling hydrogel system combining poly(N
      isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings
      with polyamidoamine-based hydrophilic and degradable diamine crosslinking
      macromers. Specifically, we studied how the parameters of GMP size and loading
      ratio affected the viability and differentiation of cells encapsulated within the
      hydrogel. We also examined the effects of cell and GMP co-encapsulation on
      hydrogel mineralization. Cells demonstrated long-term viability within the
      hydrogels, which was shown to depend on GMP size and loading ratio. In
      particular, increased interaction of cells and GMPs through greater available GMP
      surface area, use of an epoxy-based chemical gelation mechanism, and the tunable
      high water content of the thermogelled hydrogels led to favorable long-term cell
      viability. Compared with cellular hydrogels without GMPs, hydrogels co
      encapsulating cells and GMPs demonstrated greater production of alkaline
      phosphatase by cells at all time-points and a transient early enhancement of
      hydrogel mineralization for larger GMPs at higher loading ratios. Such
      injectable, in situ forming hydrogels capable of delivering and maintaining
      populations of encapsulated mesenchymal stem cells and promoting mineralization
      in vitro offer promise as novel therapies for applications in tissue engineering
      and regenerative medicine.

PMID- 24458784
TI  - WHO reports spike in number of avian flu cases.

PMID- 24458785
TI  - Ruthenium-catalyzed synthesis of indoles from anilines and epoxides.
AB  - A general synthetic route to indoles from readily available anilines and epoxides
      by using ruthenium catalysis is described. This straightforward transformation
      allows a variety of indoles to be obtained in good yields by using
      [Ru3(CO)12]/1,1'-bis(diphenylphosphino)ferrocene as the catalytic system. Water
      and hydrogen are formed as the only stoichiometric by-products, making this
      process highly atom efficient.

PMID- 24458786
TI  - Temperature-responsive microgel films as reversible carbon dioxide absorbents in
      wet environment.
AB  - Hydrogel films composed of temperature-responsive microgel particles (GPs)
      containing amine groups work as stimuli-responsive carbon dioxide absorbent with
      a high capacity of approximately 1.7 mmol g(-1). Although the dried films did not
      show significant absorption, the reversible absorption capacity dramatically
      increased by adding a small amount of water (1 mL g(-1)). The absorption capacity
      was independent of the amount of added water beyond 1 mL g(-1), demonstrating
      that the GP films can readily be used under wet conditions. The amount of CO2
      absorbed by the GP films was proportional to their thickness up to 200-300 MUm
      (maximum capacity of about 2 L m(-2) . Furthermore, the films consisting of GPs
      showed faster and greater absorption and desorption of CO2 than that of
      monolithic hydrogel films. These results indicated the importance of a fast
      stimulus response rate of the films that are composed of GPs in order to achieve
      long-range and fast diffusion of bicarbonate ions. Our study revealed the
      potential of stimuli-responsive GP films as energy-efficient absorbents to
      sequester CO2 from high-humidity exhaust gases.

PMID- 24458788
TI  - The physico-chemical basis of leaf wettability in wheat.
AB  - Wild type wheat (Triticum aestivum L.) and three mutant lines that have reduced
      glaucousness on the flag leaf sheath have been examined for variations in
      glaucousness, contact angles, wax chemistry and wax morphology. On the sheath and
      culm, organs that are glaucous in the wild type, increasing glaucousness is
      correlated with increasing contact angles, an increasing proportion of beta
      diketones plus hydroxy-beta-diketones in the was and an increasing proportion of
      wax tubes. Organs that were non-glaucous in all four lines, namely both surfaces
      of the vegetative leaves and the adaxial surface of the flag leaf, had high
      contact angles, a dense covering of wax plates and waxes rich in primary alcohols
      but devoid of beta-diketones and hydroxy-beta-diketones. The abaxial surface of
      the flag leaf was the most complex of the organ surfaces studied. In the wild
      type the glaucousness of the sheath continued onto this surface for 1-2 cm and
      this was correlated with the other characters studied as it was on the sheath. In
      the mutants, however, the tubes were absent. Flat ribbons of varying widths, a
      new wax structure in wheat, as well as various types of plates were found
      instead. These structures continued to the flag leaf tip and were also present on
      the abaxial surface of the wild type flag leaf. Changes in contact angle at the
      tip could not be correlated with the other measured parameters. 

PMID- 24458787
TI  - Conditioned medium of human adipose-derived mesenchymal stem cells mediates
      protection in neurons following glutamate excitotoxicity by regulating energy
      metabolism and GAP-43 expression.
AB  - Glutamate excitotoxicity has been implicated as one of the pathological
      mechanisms contributing to neuronal cell death and is involved in many
      neurological disorders. Stem cell transplantation is a promising approach for the
      treatment of nervous system damage or diseases. Previous studies have shown that
      mesenchymal stem cells (MSCs) have important therapeutic effects in experimental
      animal and preclinical disease model of central nervous system pathology.
      However, it is not well understood whether neurogenesis of MSCs or MSC
      conditioned-medium (CM) containing microparticles mediates therapeutic effects.
      Here, we investigated the neuroprotective effects of human adipose-derived MSCs
      (AMSCs) on cortical neurons using models of glutamate excitotoxicity. Following
      exposure to glutamate (100 MUM, 15 min), cortical neurons were co-cultured with
      either AMSCs separated by a semiporous membrane (prohibiting direct cell-cell
      contact) or with AMSC-CM for 18 h. Compared to untreated control groups, AMSCs
      and AMSC-CM partially and similarly reduced neuronal cell damages, as indicated
      by reduced LDH release, a decreased number of trypan-positive cells and a decline
      in the number of apoptotic nuclei. Protection by CM was associated with increased
      GAP-43 expression and an elevated number of GAP-43-positive neurites.
      Furthermore, CM increased levels of ATP, NAD(+) and NADH and the ratio of
      NAD(+)/NADH, while preventing a glutamate-induced decline in mitochondrial
      membrane potential. These results demonstrate that AMSC-CM mediates direct
      neuroprotection by inhibiting neuronal cell damage/apoptosis, promoting nerve
      regeneration and repair, and restoring bioenergy following energy depletion
      caused by glutamate excitotoxicity.

PMID- 24458789
TI  - Induction of nitrate reductase by chloramphenicol in detached cucumber
      cotyledons.
AB  - Chloramphenicol (CAP) induced nitrate reductase activity (NRA) in detached,
      etiolated cucumber (Cucumis sativus L.) cotyledons. The effect was reduced by
      cycloheximide. Light was not necessary for induction of the enzyme but
      potentiated the effect of CAP as an inducer of NRA, despite the fact that the
      antibiotic inhibited chlorophyll accumulation.CAP at suboptimal concentrations
      (2.5-5 mM) acted synergistically with succinic acid-2,2-dimethylhydrazide (B
      Nine) and benzylaminopurine (BAP) in respect to induction of NRA, the effect
      being especially marked in darkness. The highest NRA was found in cotyledons
      treated for 24 h with a mixture of CAP+BAP+B-Nine. The effects of KNO3 and CAP on
      NRA were neither synergistic nor additive.KNO3 and BAP induced NADH-NR (EC
      1.6.6.1). The same was true for CAP and B-Nine, but the latter two compounds
      induced, in addition, some activity of another NR that could utilize NADPH as an
      electron donor. 

PMID- 24458790
TI  - The effects of temperature and IAA concentration on the latent period for IAA
      induced rapid growth of Avena coleoptile segments.
AB  - Indoleacetic acid buffered at pH 7.0 induces a high growth rate in Avena
      coleoptile segments after a latent period, the duration of which is dependent
      upon both IAA concentration and temperature. A minimum latent period of 7.3 min
      is observed at 25 degrees  C with 10(-3) M IAA in phosphate buffer at pH 7.0.In
      contrast, 5*10(-3) M IAA made up in 0.01 M KH2PO4 alone, promotes elongation
      almost immediately, regardless of whether the segments have been previously
      incubated in 0.01 M KH2PO4 at pH 4.7, or phosphate buffer at pH 7.0. This
      immediate response is unaffected by 10(-4) M KCN which abolishes the rapid growth
      induced by 5*10(-3) M IAA buffered at pH 7.0 but does not affect the immediate
      appearance of low-pH-induced growth. Since we consistently find solutions of
      5*10(-3) M IAA in 0.01 M KH2PO4 to have a pH of 3.5, our results indicate that
      the immediate growth response elicited by this solution is attributable to its
      low pH rather than to the presence of IAA as previously reported in the
      literature. 

PMID- 24458791
TI  - Acid-induced growth and the geotropic response of the wheat node.
AB  - Growth is initiated in segments of the leaf sheath base of Triticum aestivum by
      gravitational stimulation and by incubation in buffer solutions of pH 3. Both
      responses involve only an increase in segment length, are rapidly terminated on
      removal of the stimulus, have a similar Q10 and are dependent upon cell turgor.
      They differ, however, in that the response to acid solutions is rapid and
      unaffected by anoxia. Acid-induced growth can be stopped and started repeatedly
      by changing the pH, an increase in pH from 3 to 5 or 7 being sufficient to
      terminate the response. The maximum growth induced by low pH is not increased by
      simultaneous stimulation by gravity. 

PMID- 24458792
TI  - Light-induced chloroplast rearrangements and their action spectra as measured by
      absorption spectrophotometry.
AB  - A new combination technique of using both dual-wavelength and opalglas methods
      for scanning translucent biological samples was applied to leaves of terrestrial
      plants in order to observe their absorption changes by irradiation and the action
      spectra for the absorption changes. The measurements of true absorption, free
      from various effects of scattering, by this technique showed an increase of
      absorption by weak blue light and a decrease of absorption by strong blue light
      for almost all of the leaves of 20 plant species examined. These weak- and strong
      light responses in absorption were reversible. The fractional increase and
      decrease of absorbance at 678 nm by weak and strong light were highest, +20% and 
      31%, for leaves of Begonia semperflorens Link et Otto, and +12% and -13% for
      leaves of foxtail, Setaria viridis (L.) Beauv., the species examined in further
      experiments. The response to strong light proceeded to completion earlier than
      did that to weak light. The strong-light response could be observed separately
      from the weak-light response by using a leaf pre-irradiated with weak blue light.
      The responses were measured as a function of light intensity by scanning a single
      leaf irradiated locally at different intensities, and the action spectra for
      these responses were measured by scanning a leaf irradiated locally at different
      wavelengths but at identical intensities. The action spectra for these opposite
      responses were similar, and showed a band at 450 nm with shoulders but no band in
      the red region. Microscopic observations of chloroplasts in leaves during
      irradiation indicated that these changes in absorption are mostly due to
      rearrangements of chloroplasts in cells caused by irradiation. 

PMID- 24458793
TI  - Reinvestigation of apple-seed gibberellins.
AB  - Re-investigation of the gibberellins in apple seed has established the presence
      of GA4 and GA7 and of traces of GA9. The fraction, previously considered to be
      GA7 by TLC, contains small amounts of GA4 and traces of GA9; and the fraction,
      characterized as GA4 by TLC, contains traces of GA7 and GA9. However the present
      results do not change the previous conclusions that during the stratification of
      apple seed the level of GA7 remains fairly constant while that of GA4 increases. 

PMID- 24458794
TI  - [The distribution pattern of phosphoenolpyruvate-carboxykinase and ribulose-1,5
      diphosphate carboxylase activities in fronds of Laminaria hyperborea (Gunn.)
      Fosl].
AB  - High activities of phosphoenolpyruvate-carboxykinase (EC 4.1.1.32) have been
      found in fronds of the brown alga Laminaria hyperborea (Gunn.) Fosl. The
      distribution pattern of this enzyme in the newly formed and in the old phylloid
      (last year's production) and in the cauloid was investigated and compared with
      that of ribulose-1,5-diphosphate carboxylase (EC 4.1.1.39). Maximum activity of
      both enzymes is located in the growing region of the new phylloid. In the other
      parts of the frond, enzyme activity is only about one tenth of the values
      estimated for the intercalary meristem. The activity of PEP-carboxykinase: RuDP
      carboxylase shifts from approxymately 9 in the growing region to only 3 in the
      old phylloid. 

PMID- 24458795
TI  - [Dorsiventrality of statocytes in plagiogeotropic lateral roots of Lepidium
      sativum L].
AB  - The calyptra of plagiotropic lateral roots of Lepidium sativum L. is composed of
      three rows of cells. Movable amyloplates, possibly functioning as statoliths, are
      located only a few central cells of the ontogenetic youngest cell row. Beside the
      lateral root axis the two innermost statocytes contain a stable complex of rough
      endoplasmic reticulum, which is preferentially located in the central distal cell
      corner. In the statocytes lying above the lateral root axis the amyloplasts are
      sedimented on the ER-complex during growth in direction of the geotropic liminal
      angle. In the statocyte below the axis the ER-complex is free of amyloplasts.
      Thus a dorsiventrality exists in the statocytes located above and below the root
      axis in regard to the arrangement of their organelles. 

PMID- 24458796
TI  - Observation of antennal sensilla in Xylotrechus grayii (Coleoptera: Cerambycidae)
      with scanning electron microscopy.
AB  - The longicorn beetle Xylotrechus grayii (White, 1855) has been spreading rapidly
      in China, causing mass mortality of honeysuckle which is economically and
      medicinally important. In order to elucidate the mechanisms of mate and host
      location and to advance efficient control methods, antennal sensilla features
      were investigated in both sexes of X. grayii using scanning electron microscopy
      (SEM). The filiform antennae of both sexes consist of scape, pedicel, and nine
      flagellomeres (f1-9). Five types of sensilla were observed: sensilla chaetica (5
      subtypes, SC1-5), sensilla basiconica (4 subtypes, SB1-4), Bohm bristles (Bm),
      grooved peg sensilla (Gp), and sensilla campaniformia (Ca). SC were most common
      on the antennae, followed by SB and Bm. No significant sexual differences in the
      type, amounts, and distribution of antennal sensilla were found except for the
      distribution of SB clusters and Ca. SB clusters and Ca occurred on f1-8 of male
      antennae but were absent on those segments in females, suggesting a potential
      function as receptors for female sex pheromones. The putative functions of other
      sensilla are discussed based on their characteristics in related species. This
      study provides an important foundation for further research on sensory mechanisms
      and control measures of X. grayii.

PMID- 24458797
TI  - Post-radical hysterectomy detrusor dysfunctions: is sacral neurostimulation a
      valid treatment strategy?

PMID- 24458798
TI  - Long-term observation of a patient with dominant omodysplasia.
AB  - We report on the natural history of a female with dominant omodysplasia, a rare
      osteochondrodysplasia with short stature, rhizomelia of the extremities (upper
      extremities more affected), and short first metacarpals. The proband had normal
      molecular analysis of the glypican 6 gene (GPC6), which was recently reported as
      a candidate for autosomal recessive omodysplasia. The findings in this patient
      were compared to other known and suspected cases of autosomal dominant
      omodysplasia. Mild rhizomelic shortening of the lower extremities has not been
      previously reported.

PMID- 24458799
TI  - MECP2 duplication: possible cause of severe phenotype in females.
AB  - MECP2 duplication syndrome, originally described in 2005, is an X-linked
      neurodevelopmental disorder comprising infantile hypotonia, severe to profound
      intellectual disability, autism or autistic-like features, spasticity, along with
      a variety of additional features that are not always clinically apparent. The
      syndrome is due to a duplication (or triplication) of the gene methyl CpG binding
      protein 2 (MECP2). To date, the disorder has been described almost exclusively in
      males. Female carriers of the duplication are thought to have no or mild
      phenotypic features. Recently, a phenotype for females began emerging. We
      describe a family with ~290 kb duplication of Xq28 region that includes the MECP2
      gene where the proposita and affected family members are female. Twin sisters,
      presumed identical, presented early with developmental delay, and seizures.
      Evaluation of the proposita at 25 years of age included microarray comparative
      genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same
      duplication was found in the proposita's sister, who is more severely affected,
      and the proband's mother who has mild intellectual disability and depression. X
      chromosome inactivation studies showed significant skewing in the mother, but was
      uninformative in the twin sisters. We propose that the MECP2 duplication caused
      for the phenotype of the proband and her sister. These findings support evidence
      for varied severity in some females with MECP2 duplications.

PMID- 24458800
TI  - Reply to the letter to the editor entitled "clinical predictors of long-term
      outcomes in patients with critical limb ischemia who have undergone endovascular
      therapy".

PMID- 24458801
TI  - The effect of adding ezetimibe to rosuvastatin on renal function in patients
      undergoing elective vascular surgery.
AB  - We compared the effects of lipid lowering with rosuvastatin (RSV) monotherapy
      versus intensified treatment by combining RSV with ezetimibe (EZT) on kidney
      function in patients undergoing vascular surgery. Patients were randomly assigned
      to either 10 mg/d RSV (n = 136) or RSV 10 mg/d plus EZT 10 mg/d (RSV/EZT, n =
      126). At 12 months, a similar decrease in estimated glomerular filtration rate
      (eGFR) was noted. Patients who achieved a low-density lipoprotein cholesterol
      (LDL-C) of <100 mg/dL had less eGFR decrease than those patients having an LDL-C
      limit of more than 100 mg/dL. There were no significant changes in the urinary
      total protein to creatinine ratio in either group. Significant microalbuminuria
      was evident in both the groups. Patients undergoing vascular surgery show
      deterioration in their renal function during the first year, despite statin
      therapy. Intensified lipid-lowering therapy by adding EZT does not appear to have
      any renoprotective effect. 

PMID- 24458802
TI  - Serum uric acid concentration and asymptomatic hyperuricemia.

PMID- 24458803
TI  - Letter to the editor.

PMID- 24458804
TI  - Serum bilirubin level and aortic intima-media thickness in patients without
      clinical manifestation of atherosclerotic cardiovascular disease.

PMID- 24458805
TI  - The Massachusetts school-based body mass index experiment: gleaning
      implementation lessons for future childhood obesity reduction efforts.
AB  - In 2009, Massachusetts (MA) Department of Public Health (DPH) implemented new
      regulations that required public schools in the state to measure height and
      weight, determine body mass index (BMI), and notify parents of children in grades
      1, 4, 7, and 10 of their child's weight status. After 3 years of implementation,
      MA DPH recently abandoned parental notification of school-based BMI screening
      results citing several concerns including flaws in the ability to monitor the way
      that the BMI screening results were communicated from the schools to
      parents/guardians and some reports of breaches in confidentiality of students'
      measurements. In this article, we review implementation issues that could have
      impacted the success of the MA DPH regulation as well as lessons to be learned
      and potentially applied to future childhood obesity efforts. 

PMID- 24458806
TI  - Is ventilation tube placement beneficial during tympanoplasty for atelectatic
      tympanic membranes?

PMID- 24458807
TI  - Pre-anthropocene mercury residues in North American freshwater fish.
AB  - Mercury (Hg) has been entering the environment from both natural and
      anthropogenic sources for millennia, and humans have been influencing its
      environmental transport and fate from well before the Industrial Revolution.
      Exposure to Hg (as neurotoxic monomethylmercury [MeHg]) occurs primarily through
      consumption of finfish, shellfish, and marine mammals, and regulatory limits for
      MeHg concentrations in fish tissue have steadily decreased as information on its
      health impacts has become available. These facts prompted us to consider 2
      questions: 1) What might the MeHg levels in fish tissue have been in the pre
      Anthropocene, before significant human impacts on the environment? and 2) How
      would these pre-Anthropocene levels have compared with current regulatory
      criteria for MeHg residues in fish tissue? We addressed the first question by
      estimating pre-Anthropocene concentrations of MeHg in the tissues of prey and
      predatory fish with an integrated Hg speciation, transport, fate, and food web
      model (SERAFM), using estimated Hg concentrations in soil, sediment, and
      atmospheric deposition before the onset of significant human activity (i.e.,
      <=2000 BCE). Model results show MeHg residues in fish varying depending on the
      characteristics of the modeled water body, which suggests that Hg in fish tissue
      is best considered at the scale of individual watersheds or water bodies. We
      addressed the second question by comparing these model estimates with current
      regulatory criteria and found that MeHg residues in predatory (but not prey) fish
      could have approached or exceeded these criteria in some water bodies during the
      pre-Anthropocene. This suggests that the possibility of naturally occurring
      levels of Hg in fish below which it is not possible to descend, regardless of
      where those levels stand with respect to current regulatory limits. Risk
      management decisions made under these circumstances have the potential to be
      ineffectual, frustrating, and costly for decision makers and stakeholders alike,
      suggesting the need for regulatory flexibility when addressing the issue of Hg in
      fish.

PMID- 24458808
TI  - Over-expression of ARHI decreases tumor growth, migration, and invasion in human
      glioma.
AB  - This study was conducted to evaluate the role of tumor suppressor gene ras
      homologue member I (ARHI) in human glioma tumors. We examined expression of ARHI
      in human glioma tumors and normal brain tissue and also in 4 different glioma
      cell lines. Furthermore, the effects of ARHI over-expression produced by cellular
      transfection on the growth of human glioma U251 cells cultured in vitro were also
      studied. Expression of ARHI was evaluated in samples of glioma tumors obtained
      from 59 patients who underwent surgery at the Department of Neurosurgery, Fujian
      Medical University Union Hospital, Fuzhou, China. Ten samples of normal brain
      tissue were used as controls. Additionally, in vitro studies were conducted in
      which a recombinant vector carrying ARHI cDNA was constructed and transfected
      into U251 glioma cells with reduced expression of ARHI. Following transfection,
      the MTT assay, flow cytometry, TUNEL procedure, Transwell assay, and wound
      healing test were employed to evaluate the biological functions of ARHI in U251
      glioma cells in vitro. Analyses of mRNA and protein expression revealed that ARHI
      was significantly down-regulated in glioma tissues as well as in 4 malignant
      glioma cell lines. Over-expression of ARHI resulted in suppression of glioma cell
      proliferation, arrest of cell cycle progression, reduction in cell migration and
      invasion, and promotion of cell apoptosis. Collectively, our data highlight the
      importance of ARHI in glioma progression and provide the first biological basis
      for ARHI as a novel candidate target for gene therapy of glioma. 

PMID- 24458809
TI  - Unravelling the nature of unipolar resistance switching in organic devices by
      utilizing the photovoltaic effect.
AB  - The origin of resistive switching in organic devices is studied by photovoltaic
      methods and impedance spectroscopy. The results show that the most commonly
      proposed charging/discharging mechanisms can be excluded as working mechanism.
      There is solid evidence that resistive switching is due to the formation/rupture
      of filaments. Further, it is shown that this is a universal property of
      metal/organic/metal thin-film devices. 

PMID- 24458810
TI  - Study of the life cycle of Amblyomma dubitatum (Acari: Ixodidae) based on field
      and laboratory data.
AB  - The life cycle of Amblyomma dubitatum was described based on the seasonal
      distribution of all parasitic stages and the development periods of engorged
      ticks under different conditions of photoperiod and temperature. All stages were
      found active along the entire year in the study area. Larvae peaked from May to
      July, nymphs peaked from July to October, and females peaked from November to
      March. This pattern represents a life cycle with one generation per year with
      most of the ticks reaching adulthood during the warmest months. The analysis of
      the effect of the photoperiod on the development of A. dubitatum showed no
      indication of morphogenetic diapause. Exposure of ticks to field conditions
      indicates a delay in metamorphosis of immature stages, in the oviposition of
      females and in the incubation of eggs, which were associated with low winter
      temperatures. The results indicate that though A. dubitatum has a one year life
      cycle, more than one cohort can co-exist within the same population in a certain
      interval of time. Finally, the potential role of small rodents as hosts for
      larvae and nymphs of A. dubitatum is confirmed.

PMID- 24458811
TI  - Isoenzymes of acid phosphatase in germinating peas.
AB  - Acid phosphatase activity in pea cotyledons increases during germination. Gel
      filtration separates three isoenzymes with pH optima of 4.9, 5.6 and 6.0. The
      relative activities of these isoenzymes change during germination. The increase
      in activity is confined to two of the three isoenzymes. Density-labelling
      experiments whow that these are synthesised de novo. Activity of the third
      isoenzyme, which is present in dry seeds, does not change significantly during
      germination, and is not affected by cycloheximide but is lost on freezing. The
      possible localization of each isoenzyme is discussed in the light of these
      findings and in relation to histochemical studies. 

PMID- 24458812
TI  - Identification of gibberellins A20 and A 29 in seed of Pisum sativum cv. Progress
      No. 9 by combined gas chromatography-mass spectrometry.
AB  - The gibberellin A1 (GA1)-like and GA5-like fractions from immature seeds of Pisum
      sativum cv. Progress No. 9 were identified by combined gas chromatography-mass
      spectrometry as GA29 and GA20 respectively. 

PMID- 24458813
TI  - Cell wall assembly in vitro from Chlamydomonas reinhardi.
AB  - The conditions for in vitro dissociation and reassembly of the cell wall of
      Chlamydomonas reinhardi have been investigated. The cell wall dissociates in
      aqueous 8 M lithium chloride to two homogeneous components (6.8 S20w and 9.3
      S20w)and dialysis of the cell wall subunits against water causes reassembly of a
      product having the same overall morphology and chemically similar to the original
      cell walls. Cell wall subunits in 8 M lithium chloride alone do not reassemble on
      dialysis against water to form cell walls but a nucleation centre has to be
      provided. 

PMID- 24458814
TI  - [Correlation of the uptake of nitrate, nitrite and phosphate to the
      photosynthetic reduction of nitrate and nitrite and to the ATP-level in
      Ankistrodesmus braunii].
AB  - The pH-dependence of NO 3 (-) and NO 2 (-) uptake is different from that of
      phosphate uptake, but similar to that of sulfate uptake, with optima between pH
      7.4 and 8.2 and smaller peaks at higher H(+)-concentration.Since the ATP-level is
      not affected by addition of ions and since phosphate uptake is not depressed by
      NO 3 (-) , the inhibition of phosphate uptake by K(+) reported in former papers
      cannot be explained by competition for the available energy(ATP) at the site of
      uptake.NO 3 (-) uptake is strongly dependent on the activity of the NO 3 (-)
      reducting system, as can be seen from the inhibition of NO 3 (-) uptake in light
      by N2 compared with that in air. Furthermore, the pH-dependences of NO 3 (-) and
      NO 2 (-) uptake correspond to the pH-optima known for the reductases.Phosphate
      uptake is enhanced by NO 3 (-) and NO 2 (-) in N2. Since the enhancement of
      phosphate uptake is sensitive to DCMU and since this DCMU-sensitive phosphate
      uptake is accompanied by O2-evolution, it is probably due to an NO 3 (-) 
      stimulated noncyclic photophosphorylation which enhances the ATP-turnover and
      hence the incorporation of phosphate into organic compounds. 

PMID- 24458815
TI  - Hydrolysed walls in the water-conducting cells of Dendroligotrichum (bryophyta):
      Histochemistry and ultrastructure.
AB  - Histochemical techniques and electron microscopy have been used to investigate
      the nature of the oblique primary end-walls of the water-conducting cells
      (hydroids) of Dendroligotrichum dendroides. (Hedw.) Broth. The observed
      properties (weakly birefringent; IKI-H2SO4-positive; periodic acid/Schiff
      negative; toluidine blue O-negative) support the conclusion that these end-walls
      are the cellulose residue of a primary wall that has been hydrolysed during
      autolysis of the hydroids. The walls are now referred to as hydrolysed end-walls.
      The unhydrolysed lateral-walls appear to be protected from hydrolytic attack by
      lignin or a lignin-like compound within those walls. The similarities between the
      hydrolysed end-walls of the hydroids and the hydrolysed walls of vascular plant
      tracheary elements are discussed. 

PMID- 24458816
TI  - No uptake of anions required by opening stomata of Vicia faba: Guard cells
      release hydrogen ions.
AB  - Epidermal strips from leaves of Vicia faba L. with ruptured epidermal cells and
      intact guard cells were exposed to solutions of K(+) in association with non
      absorbable anions. KCl served as control. Stomata exposed to a range of
      concentrations of K iminodiacetate, K 4,4-dimethyl-4,7-diazadecane-1,10
      disulfonate and K benzene sulfonate opened as widely as on KCl, indicating that
      K(+) can be taken up by guard cells without the necessity of an anion traveling
      along. Electroneutrality was maintained by an exchange of K(+) for H(+). Release
      of H(+) from guard cells was recorded as a drop in the pH of the solution on
      which the epidermal samples floated. Formation of acid equivalents by the guard
      cells was also recorded by automatic titration of the bathing solution at
      constant pH while CO2 was continuously being removed. A considerable amount of
      H(+) was released from the epidermis by ion exchange (about 8x10(-10) eq/mm(2)).
      Subtracting this quantity from the total amount of H(+) titrated resulted in an
      estimate of acid production during stomatal opening of 1.2 to 7x10(-10) eq/mm(2)
      or 1.5 to 8.5x10(-12) eq/stoma. These amounts are equivalent to the known
      capacity of the guard cells of Vicia faba to absorb K(+). 

PMID- 24458817
TI  - Respiration and oxygen transport in soybean nodules.
AB  - The respiration rate of individual soybean (Glycine max Merr.) nodules was
      measured as a function of pO2 and temperature. At 23 degrees , as the pO2 was
      increased from 0.1 to 0.9 atm, there was a linear increase in respiration rate.
      At 13 degrees , similar results were obtained, except that there was an abrupt
      saturation of respiration at approximately 0.5 atm pO2. When measurements were
      made on the same nodule, the rate of increase in respiration with pO2 was the
      same at 13 degrees  and 23 degrees . Additional results were that 5% CO in the
      gas phase had no effect on respiration, except for a small decrease in the pO2 at
      which respiration became saturated. Also, nodules still attached to the soybean
      root displayed the same respiratory behavior as detached nodules. A model for
      oxygen transport in the nodule is presented which explains these results
      quantitatively. The essence of the model is that the respiration rate of the
      central tissue of the nodule is almost entirely determined by the rate of oxygen
      diffusion to the respiratory enzymes. Evidence is given that the nodule cortex is
      the site of almost all of the resistance to oxygen diffusion within the nodule. 

PMID- 24458818
TI  - Gibberellin A20 in seed of Pisum sativum L., cv. Alaska.
AB  - The main gibberellin in immature seed of Pisum sativum L., cv. Alaska, is
      identified as GA20 by GC-MS. GA9 may also be present. 

PMID- 24458819
TI  - The effects of gelatin on aggregation of protoplasts from higher plants.
AB  - Aggregation of protoplasts of Allium fistulosum L., Brassica chinensis L. and
      Daucus carota L. was induced in great frequency with gelatin and early products
      of gelatin degradation. The optimal gelatin concentration was 2-5%. The
      aggregated protoplasts fused into groups and cell walls were formed around them
      in culture. 

PMID- 24458820
TI  - Simple brominated phenols in the bluegreen alga Calothrix brevissima West.
AB  - Through the use of gas chromatography-mass spectrometry techniques two simple
      brominated phenols, 2,3-dibromo-4,5-dihydroxybenzyl alcohol (lanosol) and 3,5
      dibromo-p-hydroxybenzyl alcohol, were identified in an axenically cultured
      bluegreen alga, Calothrix brevissima. The alga was grown in a mineral medium
      supplemented with 1% glucose and 0.075% NaBr for 3 weeks. The culture filtrate
      contained two tribrominated phenols, 2,3,5-tribromo-p-hydroxybenzyl alcohol and
      2,3,5-tribromo-p-hydroxybenzaldehyde, and traces of lanosol. 

PMID- 24458821
TI  - Direct flower neoformation from superficial tissue of small explants of Nicotiana
      tabacum L.
AB  - On explants composed of 3-6 layers of epidermal and sub-epidermal cells of
      Nicotiana tabacum L. from the floral branches, it is possible to obtain mitoses
      followed very rapidly by meioses and the direct formation of anthers and pistil
      without any intermediate callus. 

PMID- 24458822
TI  - Location of ethylene production in cotton flowers and dehiscing fruits.
AB  - Over half of the ethylene produced by 1-day-old cotton flowers came from the
      combined stigma, style, and stamens. These tissues produced 0.0050 MUl/flower.h
      compared to 0.0024 and 0.0010 MUl/flower.h produced by the petals and ovary,
      respectively. Walls of dehiscing cotton fruits produced 0.052 MUl
      ethylene/fruit.h. This was approximately 50% more than seeds plus fiber which
      produced 0.033 MUl/fruit.h. 

PMID- 24458823
TI  - Porcine ubiquitin-like 5 (UBL5) gene: genomic organization, polymorphisms, mRNA
      cloning, splicing variants and association study.
AB  - Ubiquitin-like 5 (UBL5), which is supposed to be involved in regulation of feed
      intake, energy metabolism, obesity and type 2 diabetes, is located at position
      62.1 cM on the pig chromosome 2 region harbouring quantitative trait loci for
      carcass and meat quality. The 4,354 bp genomic sequence (FR798948) of the porcine
      gene encompassing the promoter and entire gene was cloned by polymerase chain
      reaction. Comparative sequencing revealed 13 polymorphisms in noncoding regions.
      Synthesis of full-length cDNA sequences using rapid amplification of 5' and 3'
      ends showed three splice variants. Variants 1 and 2 differ in transcription
      length for the untranslated part of exon 1 with deduced protein of 73 amino acid
      (aa) residues and 100 % identities between human, mouse and other species.
      Variant 3, with 4 bp deletion at the 3' end of exon 2, encodes a truncated
      protein with 28 aa residues. In a Wild boar*Meishan F2 population (n = 334) with
      47 recorded traits, loci FR798948:g.2788G>A and FR798948:g.2141T>C were
      associated at nominal P < 0.05 with fat deposition, growth and fattening and
      muscling but after adjustment for multiple testing (Benjamini and Hochberg, J R
      Stat Soc B 57:289-300, 1995) only eight fat deposition traits showed suggestive
      association with FR798948:g.2788G>A at adjusted P < 0.10. In a Meishan*Large
      White (MLW) cross (n = 562) with six trait records available, FR798948:g.2141T>C
      showed suggestive association with growth (adjusted P = 0.0690). As association
      mapping conducted in the outbred MLW population is more precise than in the three
      generation F2 population the UBL5 gene tends to be associated with growth rather
      than with fat accretion.

PMID- 24458824
TI  - The changes of serum proteome and tissular pathology in mouse induced by
      botulinum toxin E injection.
AB  - The experiment were performed to investigate the poisoning-related proteins and
      main pathological changes after mouse suffered from injection of botulinum toxin
      serotype E. Dose of 0.75 LD50 botulinum toxin serotype E per mice were
      administrated by intraperitoneal injection. Survival mouse were picked as
      experimental group. The blood were collected from orbital blood and serum sample
      was separated by centrifugation. The heart, liver, spleen, lung, kidney were
      fixed in 10 % neutral buffered formalin and then developed paraffin sections.
      Serum protein components were analyzed by SDS-PAGE gel electrophoresis coupled
      with 2-DE SDS-PAGE gel electrophoresis. Differentially expressed proteins were
      analyzed by PDQUest8.0 software and subjected to ion trap mass spectrometry
      equipped with a high performance liquid chromatography system. The observation of
      pathological section showed that heart, liver, spleen, lung, kidney exhibited
      pathological changes in different degree, especially in heart, liver and lung
      tissues. Heart muscle tissue display serious inflammatory response, heart muscle
      fiber compulsively expanded and filled with erythrocyte and inflammatory
      exudates, some heart muscle fiber ruptured, even necrosis; hepatic cell in edge
      of liver occur apoptosis and some hepatic cell have disintegrated, and even died;
      pulmonary alveoli broken and partial vein filled with blood. Serum proteins
      component present a significant changes between control serum and botulism in 24
      h by SDS-PAGE gel electrophoresis and 2-DE-SDS-PAGE gel electrophoresis. Twenty
      differentially expressed protein spots were observed in 2-DE profiles, in which
      14 protein spots were undetectable in serum proteome under botulism, 3 protein
      spots exclusively expressed in state of botulism, 3 protein spots were low
      expressed in serum proteome under botulism. Fourteen proteins have been
      identified among 20 spots elected on two-dimensional electrophoresis gels.
      Crystal proteins family exclusively expressed in control group serum. Haptoglobin
      were low-expressed under botulism in serum protein components, however, serum
      amyloid A only expressed in serum sample under botulism in 24 h, which were
      verified by Western-blot. Identified proteins involved in energy metabolism,
      cellular stress response, transcription, body defense and cell proliferation.
      These findings represent the first report of BoNT-induced changes in serum
      proteome and histopathology, and reinforce the utility of applying proteomic
      tools to the study of system-wide biological processes in normal and botulism.

PMID- 24458825
TI  - Association of obesity and circulating adipose stromal cells among breast cancer
      survivors.
AB  - A positive association of obesity with breast cancer incidence and mortality is
      well established. Recent reports indicate that adipose stromal cells (ASCs) play
      an important role in breast cancer development and progression by producing
      estrogens and tumor-promoting cytokines. Furthermore, circulating ASCs have been
      uniquely detected in obese individuals, which is likely due to increased tissue
      remodeling and cell mobilization. The number of circulating ASCs is even more
      prominent in obese patients with colon and prostate cancers, both of which are
      exacerbated by obesity. To determine whether a similar association exists for
      breast cancer, we collected blood samples from a cohort of breast cancer
      survivors and enumerated circulating ASCs by flow cytometry on the basis of the
      previously established ASC-associated immunophenotype (CD34+/CD31-/CD45-). We
      found significantly higher levels of circulating ASCs (p<0.001) in breast cancer
      survivors with body mass index (BMI)>=30 kg/m2 than their non-obese counterparts
      (BMI<30). We also compared circulating ASCs before and after exercise of only the
      obese subjects enrolled in a 6-month individualized exercise program, but found
      no statistically significant difference, likely due to limited number of subjects
      in the study. Our findings suggest that circulating ASCs can serve as a potential
      biomarker for future studies of the impacts of obesity and physical activity on
      breast cancer recurrence and survival.

PMID- 24458826
TI  - Identification and bioinformatic analysis of signal responsive/calmodulin-binding
      transcription activators gene models in Vitis vinifera.
AB  - In this study, 10 grapevine (Vitis vinifera) SR/CAMTA (Signal
      Responsive/Calmodulin-binding Transcription Activators) gene models were
      identified from three grapevine genome protein datasets. They belong to four gene
      groups: VvCAMTA1, VvCAMTA3, VvCAMTA4 and VvCAMTA5, which were located on
      chromosome 5, 7_random, 1 and 5, respectively. Alternative splicing could explain
      the multiple gene models in one gene group. Subcellular localization using the
      WoLF tool showed that most of the VvCAMTAs were located in the nucleus, except
      for VvCAMTA3.1, VvCAMTA3.2 and VvCAMTA5.2, which were located in the chloroplast,
      chloroplast and cytosol, respectively. Subcellular localization using TargetP
      showed that most of the VvCAMTAs were not located in the chloroplast,
      mitochondrion and secretory pathway in cells. VvCAMTA1.1 and VvCAMTA1.2 were
      located in the mitochondria. The digital gene expression profile showed that
      VvCAMTAs play important roles in Ca2+ signal transduction. The gene expression
      patterns of VvCAMTAs were different; for example, VvCAMTA1 was expressed mainly
      in the bud, while VvCAMTA3 was expressed mainly in fruit and inflorescence, with
      low expression in the bud. The results of this study make a substantial
      contribution to our knowledge concerning genes, genome annotation, and cell
      signal transduction in grapevine.

PMID- 24458827
TI  - "Letter to editor" in lieu of article published in Mol Biol Rep. 2012 May;
      39(5):5219-24. PTGS2 (COX2) -765G>C gene polymorphism and risk of sporadic
      colorectal cancer in Iranian population.

PMID- 24458828
TI  - Correlations of SELE genetic polymorphisms with risk of coronary heart disease
      and myocardial infarction: a meta-analysis.
AB  - This meta-analysis of case-control studies was conducted to determine whether
      SELE genetic polymorphisms contribute to the pathogenesis of coronary heart
      disease (CHD) and myocardial infarction (MI). The PubMed, CISCOM, CINAHL, Web of
      Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched
      for relevant articles published before November 1st, 2013 without any language
      restrictions. Meta-analysis was conducted using the STATA 12.0 software. Twenty
      case-control studies met the inclusion criteria, with a total of 2,292 CHD
      patients, 901 MI patients and 3,233 healthy controls. Six common polymorphisms in
      the SELE gene were evaluated, including 554L/F, 98G/T, 128S/R, 2692G/A, 1901C/T,
      and 1856A/G. The results of our meta-analysis suggest that SELE genetic
      polymorphisms might be strongly correlated with an increased risk of CHD (allele
      model: OR 2.08, 95% CI 1.67-2.58, P<0.001; dominant model: OR 2.12, 95% CI 1.68
      2.68, P<0.001; respectively), especially the SELE 554L/F, 98G/T and 128S/R
      polymorphisms. Furthermore, our findings indicated that SELE genetic
      polymorphisms were closely linked to the risk of CHD in Asians but not
      Caucasians. However, our findings reveal no positive correlations between SELE
      genetic polymorphisms and MI risk (allele model: OR 1.39, 95% CI 1.00-1.94,
      P=0.054; dominant model: OR 1.40, 95% CI 0.96-2.04, P=0.081; respectively). The
      current meta-analysis suggests that SELE genetic polymorphisms may contribute to
      an increased risk of CHD, especially the SELE 554L/F, 98G/T and 128S/R
      polymorphisms in Asians. However, SELE genetic polymorphisms may not be important
      determinants of susceptibility to MI.

PMID- 24458829
TI  - Postpartum development of endothelial dysfunction and oxidative stress markers in
      women with previous gestational diabetes mellitus.
AB  - BACKGROUND: Relationships between adhesion molecules (AM), oxidative stress,
      gestational diabetes mellitus (GDM) and future development of type 2 diabetes
      mellitus are unclear. AIM: We investigated AM and oxidant/antioxidant markers in
      women with previous history of GDM. SUBJECTS AND METHODS: Postpartum women with
      GDM (cases; n = 41) and healthy women (controls; n = 21) had clinical and
      laboratory variables measured, including indicators of vascular damage (ICAM-1,
      VCAM-1 and E-selectin), oxidative stress (LPO, GSH and GST) and antioxidant
      markers (catalase, SOD, GPX and TAC). RESULTS: Previous GDM versus control women
      presented higher body mass index: 27.4 +/- 5.6 versus 23.9 +/- 3.6 (p = 0.013);
      waist circumference: 85.2 +/- 12.9 versus 77.5 +/- 9.0 (p = 0.017); MetS (WHO
      definition): 14.6 versus 0 % (p = 0.012); MetS (NCEP-ATPIII definition): 22
      versus 0 % (p = 0.002); low HDL: 36.6 versus 9.5 % (p = 0.024); fasting glucose
      (mmol/L): 5.4 +/- 0.6 versus 4.9 +/- 0.2 (p < 0.001); glucose 120 min (mg/dL):
      105.0 +/- 30.2 versus 85.1 +/- 14.2 (p = 0.007); fasting insulin (MUU/mL): 13.4
      +/- 8.1 versus 8.4 +/- 4.3 (p = 0.004); HOMA index: 3.3 +/- 2.3 versus 1.8 +/-
      1.0 (p = 0.002); HbA1c (%/mmol/mol): 5.4 +/- 0.2 versus 5.2 +/- 0.2/36 +/- 1.4
      versus 33 +/- 1.4 (p = 0.021); uric acid (mg/dL): 4.1 +/- 1 versus 3.5 +/- 0.6 (p
      = 0.009); catalase (nmol/min/mL): 38.7 +/- 15.6 versus 28.9 +/- 11.1 (p = 0.013).
      There were no significant differences in hypertension prevalence, lipid
      fractions, albumin/creatinine ratio and AM. CONCLUSIONS: Women with previous GDM
      have high catalase levels which correlate positively with glucose intolerance,
      indicating the potential effect of oxidative stress on postpartum dysglycemic
      status.

PMID- 24458830
TI  - A new predictive equation for evaluating women body fat percentage and obesity
      related cardiovascular disease risk.
AB  - BACKGROUND: Obesity represents a global public health problem due to its
      association with cardiovascular diseases and reduced lifespan. The most widely
      used classification of obesity is expressed as Body Mass Index (BMI); however,
      this formula is an imprecise adiposity measurement that ignores several important
      factors involved. Body Adiposity Index (BAI) was more recently proposed as an
      indirect evaluation of percentage body fat (PBF). PBF is a direct measure of
      person's relative body fat and a better predictor of obesity-related risk
      diseases than BMI and BAI. Since obesity and consequent diseases are considered
      epidemic, new accurate formulas for epidemiological studies are of interest to
      the scientific community. Because direct measurement of body composition could be
      quite expensive, the aims of our work were to analyse the distributions of PBF by
      Dual X-ray absorptiometry, and the creation of new predictive equation using only
      anthropometric measures that could be helpful to clinicians to assess easily body
      fat of female patients. METHODS/RESULTS: A sample of 1,031 Caucasian Italian
      women was recruited and BMI, BAI and PBF were evaluated. With the aim of
      developing a predictive model of PBF a multivariate regression model was fitted
      to observed data. CONCLUSIONS: The definition of universally recognized PBF by
      gender and age could have public health implications. In this study, we developed
      a new predictive PBF equation that does not require the use of medical
      instruments or skilled measurement techniques and that may be easily applicable
      to Italian women.

PMID- 24458831
TI  - Management of adrenal cancer: a 2013 update.
AB  - Adrenocortical carcinoma (ACC) is a devastating tumor for either patients or
      their families because of short life expectancy and severe impact on quality of
      life. Due to the rarity of ACC, with a reported annual incidence of 0.5-2 cases
      per million population, progress in the development of treatment options beyond
      surgery has been limited. Up to now, no personalized approach of ACC therapy has
      emerged, apart from plasma level-guided mitotane therapy, and no simple
      targetable molecular event has been identified from preclinical studies. Complete
      surgical removal of ACC is the only potentially curative approach and has the
      most important impact on patient's prognosis. Despite the limits of the available
      evidence, adjuvant mitotane therapy is currently recommended in many expert
      centers whenever the patients present an elevated risk of recurrence. The
      management of patients with recurrent and metastatic disease is challenging and
      the prognosis is often poor. Mitotane monotherapy is indicated in the management
      of patients with a low tumor burden and/or more indolent disease while patients
      whose disease show an aggressive behavior need cytotoxic chemotherapy. The
      treatment of patients with advanced ACC may include loco-regional approaches such
      as surgery and radiofrequency ablation in addition to systemic therapies. The
      present review provides an updated overview of the management of ACC patients
      following surgery and of the management of ACC patients with advanced disease.

PMID- 24458832
TI  - Benign prostatic hyperplasia: a new metabolic disease?
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms
      (LUTS) are conditions extremely prevalent in the aging male. Although androgens
      are involved in prostate growth during developmental age, their role in the
      pathogenesis of BPH/LUTS is debated. Recent data indicate that low testosterone
      and high estradiol favor disease progression. In addition, the role of other
      determinants, such as metabolic syndrome or prostate inflammation, is emerging.
      AIM: We reviewed the evidence regarding the pathogenesis of BPH/LUTS with
      particular attention to metabolic influence. MATERIALS AND METHODS: A review of
      published evidence was performed using Medline. RESULTS: Available evidence shows
      that a three-hit hypothesis can be drawn. An overt, or even a subclinical,
      bacterial or viral infection could induce prostatic inflammation (first hit) that
      could be autosustained or exacerbated by the presence of an altered metabolism
      and in particular by hypercholesterolemia (second hit). Hypogonadism and/or
      hyperestrogenism could act as a third hit, favoring the maintenance of this
      inflammatory state. The combined action of all three hits, or even two of them,
      may result in overexpression of Toll-like receptors (TLRs), transformation of
      prostatic cells into antigen-presenting cells and activation of resident human
      prostate-associated lymphoid tissue ending in overproduction of growth factors
      which, in turn, will induce prostate remodeling and further prostate enlargement.
      The mechanical obstruction, along with the direct action of the unfavorable
      metabolic and hormonal milieu on the bladder neck, helps in generating LUTS.
      CONCLUSION: Inflammation, dyslipidemia and altered sex-steroid milieu mutually
      concur in determining BPH/LUTS.

PMID- 24458833
TI  - Effects of testosterone replacement therapy on bone metabolism in male post
      surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor
      CAG polymorphism.
AB  - INTRODUCTION AND AIM: The relationship between androgen receptor (AR) CAG
      polymorphism and bone metabolism is highly controversial. We, therefore, aimed to
      evaluate the independent role of AR CAG repeat polymorphism on bone metabolism
      improvement induced by testosterone replacement therapy (TRT) in male post
      surgical hypogonadotropic hypogonadism, a condition frequently associated with
      hypopituitarism and in which the effects of TRT have to be distinguished from
      those resulting from concomitant administration of pituitary function replacing
      hormones. METHODS: 12 men affected by post-surgical hypogonadotropic hypogonadism
      [mean duration of hypogonadism 8.3 +/- 2.05 (SD) months] were retrospectively
      assessed before and after TRT (from 74 to 84 weeks after the beginning of
      therapy). The following measures were studied: parameters of bone metabolism
      [serum markers and bone mineral density (BMD)], pituitary dependent hormones and
      genetic analysis (AR CAG repeat number). RESULTS: Total testosterone, estradiol,
      free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two
      phases, while follicle stimulating hormone (FSH) decreased. While serum markers
      did not vary significantly between the two phases, BMD improved slightly but
      significantly in all the studied sites. The number of CAG triplets correlated
      negatively and significantly with all the variations (Delta-) of BMDs.
      Conversely, Delta-testosterone correlated positively and significantly with all
      studied Delta-BMDs, while Delta-FSH, Delta-estradiol, Delta-FT4, and Delta-IGF-1
      did not correlate significantly with any of the Delta-BMDs. Multiple linear
      regression analysis, after correction for Delta-testosterone, showed that CAG
      repeat length was negatively and significantly associated with ?-BMD of all
      measured sites. CONCLUSIONS: Our data suggest that, in post-surgical male
      hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated
      with greater TRT-induced improvement of BMD.

PMID- 24458835
TI  - JAK2V617F monitoring in polycythemia vera and essential thrombocythemia: clinical
      usefulness for predicting myelofibrotic transformation and thrombotic events.
AB  - The JAK2V617F allele burden has been identified as a risk factor for vascular
      events and myelofibrotic transformation in polycythemia vera (PV) and essential
      thrombocythemia (ET). However, all previous studies have evaluated a single time
      point JAK2V617F measurement. Therefore, the frequency and the clinical
      significance of changes in the JAK2V617F mutant load occurring during the disease
      evolution remain unknown. In the present study, JAK2V617F monitoring was
      performed during the follow-up of 347 patients (PV = 163, ET = 184). According to
      their JAK2V617F evolutionary patterns, patients were stratified as stable < 50%
      (n = 261), stable >=50% (n = 52), progressive increase (n = 24) and unexplained
      decrease (n = 10). After a 2,453 person-years follow-up, a total of 59 thrombotic
      events, 16 major hemorrhages, and 27 cases of myelofibrotic transformations were
      registered. At multivariate analyses, patients with a persistently high (>=50%)
      or unsteady JAK2V617F load during follow-up had an increased risk of
      myelofibrotic transformation (Incidence rate ratio [IRR]: 20.7, 95% CI: 6.5-65.4;
      P < 0.001) and a trend for a higher incidence of thrombosis (IRR: 1.7, 1-3.3; P =
      0.05) than patients with a stable allele burden below 50%. In conclusion,
      JAK2V617F monitoring could be useful in patients with PV and ET for predicting
      disease's complications, especially myelofibrotic transformation.

PMID- 24458838
TI  - Blood-brain barrier permeability of bioactive withanamides present in Withania
      somnifera fruit extract.
AB  - The neuroprotective effect of Withania somnifera L. Dunal fruit extract, in
      rodent models, is known. Withanamides, the primary active constituents in
      W.somnifera fruit extract exhibited neuroprotective effects against beta-amyloid
      induced cytotoxicity in neuronal cell culture studies. Therefore, we investigated
      the blood-brain barrier permeability of withanamides in W.somnifera fruit extract
      in mice using HPLC coupled with high resolution quadrupole time of flight mass
      spectrometer (Q-TOF/MS) detection. Mice were administered with 250 mg/kg of
      W.somnifera extract by intraperitoneal injection, and the blood and brain samples
      analyzed by Q-TOF/MS detection. Four major withanamides were detected in brain
      and blood of mice administered with W.somnifera extract. The results suggested
      that the withanamides crossed the blood-brain barrier. These results may help to
      develop W.somnifera fruit extract as a preventive or therapeutic botanical drug
      for stress-induced neurological disorders.

PMID- 24458839
TI  - Blue sky commissioning.

PMID- 24458834
TI  - Relevance of genetic investigation in male infertility.
AB  - Genetic causes can be directly responsible for various clinical conditions of
      male infertility and spermatogenic impairment. With the increased use of assisted
      reproduction technologies our understanding of genetic basis of male infertility
      has large implications not only for understanding the causes of infertility but
      also in determining the prognosis and management of such couples. For these
      reasons, the genetic investigations represent today an essential and useful tool
      in the treatment of male infertility. Several evidences are available for the
      clinical practice regarding the diagnosis; however, there are less information
      relative to the treatment of the genetic causes of male infertility. Focus of
      this review is to discuss the main and more common genetic causes of male
      infertility to better direct the genetics investigation in the treatment of
      spermatogenic impairment. 

PMID- 24458836
TI  - Modifications in parent feeding practices and child diet during family-based
      behavioral treatment improve child zBMI.
AB  - OBJECTIVE: To examine associations between modifications in parent feeding
      practices, child diet, and child weight status after treatment and to evaluate
      dietary mediators. METHODS: Children classified as overweight or obese and 7-11
      years old (N = 170) completed a 16-session family-based behavioral weight loss
      treatment (FBT) program. Anthropometrics (standardized body mass index (zBMI)),
      Child Feeding Questionnaire, and 24-hr dietary recalls were collected at baseline
      and post-FBT. Linear regression predicted child zBMI change. Single and multiple
      mediation tested child dietary modifications as mediators between change in
      parent feeding practices and child zBMI. RESULTS: Restrictive parent feeding
      practices significantly decreased during FBT. Reductions in parent restriction,
      child weight concern, child's total energy intake, and percent energy from fat,
      and increases in parent perceived responsibility, and child percent energy from
      protein, predicted reductions in child zBMI. Change in child total energy intake
      mediated the relation between parent restriction and child zBMI change after
      accounting for covariates and additional dietary mediators. CONCLUSIONS: FBT is
      associated with a decrease in parental restriction, which is associated with
      reductions in child relative weight, which was mediated by a decrease in child
      energy intake. Teaching parents to reduce children's energy intake without being
      overly restrictive may improve child weight.

PMID- 24458840
TI  - Cool-1-mediated inhibition of c-Cbl modulates multiple critical properties of
      glioblastomas, including the ability to generate tumors in vivo.
AB  - We discovered that glioblastoma (GBM) cells use Cool-1/beta-pix to inhibit normal
      activation of the c-Cbl ubiquitin ligase via the redox/Fyn/c-Cbl pathway and that
      c-Cbl inhibition is critical for GBM cell function. Restoring normal c-Cbl
      activity by Cool-1 knockdown in vitro reduced GBM cell division, almost
      eliminated generation of adhesion-independent spheroids, reduced the
      representation of cells expressing antigens thought to identify tumor initiating
      cells (TICs), reduced levels of several proteins of critical importance in TIC
      function (such as Notch-1 and Sox2), and increased sensitivity to BCNU
      (carmustine) and temozolomide (TMZ). In vivo, Cool-1 knockdown greatly suppressed
      the ability of GBM cells to generate tumors, an outcome that was c-Cbl dependent.
      In contrast, Cool-1 knockdown did not reduce division or increase BCNU or TMZ
      sensitivity in primary glial progenitor cells and Cool-1/c-Cbl complexes were not
      found in normal brain tissue. Our studies provide the first evidence that Cool-1
      may be critical in the biology of human tumors, that suppression of c-Cbl by Cool
      1 may be critical for generation of at least a subset of GBMs and offer a novel
      target that appears to be selectively necessary for TIC function and modulates
      chemoresistance in GBM cells. Targeting such proteins that inhibit c-Cbl offers
      potentially attractive opportunities for therapeutic development.

PMID- 24458841
TI  - CXCR4 expression accounts for clinical phenotype and outcome in acute myeloid
      leukemia.
AB  - Background. In acute myeloid leukemia (AML), CXCR4 expression has been correlated
      with leukocytosis and prognosis. Methods. We quantified CXCR4 expression by flow
      cytometry on leukemic cells in 142 AML patients. Results. We confirm a
      correlation between high CXCR4 expression and leukemic burden. Furthermore, we
      documented a correlation with platelet count, dysplastic megakaryopoiesis, hepato
      splenomegaly and extra-hematological disease. NPM1-mutated AML displayed a
      significantly higher intensity of CXCR4 compared to NPM1-wt cases: it is
      conceivable its clinical phenotype to be driven by high CXCR4 expression.
      Conclusions. CXCR4 expression resulted an independent prognostic factor. Our data
      support CXCR4 targeting as a potential therapeutic strategy. (c) 2014 Clinical
      Cytometry Society.

PMID- 24458842
TI  - Mycorrhizal responses in wheat: shading decreases growth but does not lower the
      contribution of the fungal phosphate uptake pathway.
AB  - Effects have been investigated of reduced C supply (induced by shade) on
      arbuscular mycorrhizal (AM) colonisation, mycorrhizal growth responses (MGRs) and
      on AM-mediated and direct uptake of phosphate (Pi) (using (32)P) in wheat, a
      plant that does not usually respond positively to AM colonisation. Shading
      markedly reduced growth and shoot/root dry weight ratios of both AM and non
      mycorrhizal wheat, indicating decreased photosynthetic C supply. However, shading
      had very little effect on percent root length colonised by Rhizophagus
      irregularis or Gigaspora margarita or on MGRs, which remained slightly positive
      or zero, regardless of shade; there were no growth depressions under shade. By 6
      weeks, when the contributions of the AM pathway were measured with (32)P supplied
      in small hyphal compartments, R. irregularis had supplied 23 to 28% of shoot P
      with no significant effect of shading. Data show that reduced C availability did
      not reduce the contribution of the AM pathway to plant P, so the fungi were not
      acting physiologically as parasites. These results support our previous
      hypothesis that lack of positive MGR is not necessarily the outcome of excessive
      C use by the fungi or failure to deliver P via the AM pathway.

PMID- 24458843
TI  - A syndrome of facial dysmorphism, cubital pterygium, short distal phalanges, swan
      neck deformity of fingers, and scoliosis.
AB  - We report on an adolescent girl with sparse scalp hair, wide columella extending
      below alae nasi, webbing at elbows, broad finger tips, short distal phalanx of
      fingers, swan neck deformity of fingers, scoliosis, tall vertebrae, short
      fibulae, short fourth metatarsal bone, abnormal distal humeri, and unilateral
      clubfoot at birth. The combination of these features represents a novel
      phenotype. We sequenced the protein-coding regions of the FLNA and FLNB genes and
      did not observe any pathogenic sequence variation. Chromosomal microarray
      revealed a de novo copy number variation of uncertain clinical significance on
      7p22.3.

PMID- 24458844
TI  - Steroid hormone receptor expression in breast cancer stroma.

PMID- 24458846
TI  - Polymer-assisted metal deposition (PAMD): a full-solution strategy for flexible,
      stretchable, compressible, and wearable metal conductors.
AB  - Metal interconnects, contacts, and electrodes are indispensable elements for most
      applications of flexible, stretchable, and wearable electronics. Current
      fabrication methods for these metal conductors are mainly based on conventional
      microfabrication procedures that have been migrated from Si semiconductor
      industries, which face significant challenges for organic-based compliant
      substrates. This Research News highlights a recently developed full-solution
      processing strategy, polymer-assisted metal deposition (PAMD), which is
      particularly suitable for the roll-to-roll, low-cost fabrication of high
      performance compliant metal conductors (Cu, Ni, Ag, and Au) on a wide variety of
      organic substrates including plastics, elastomers, papers, and textiles. This
      paper presents i) the principles of PAMD, and how to use it for making ii)
      flexible, stretchable, and wearable conductive metal electrodes, iii) patterned
      metal interconnects, and d) 3D stretchable and compressible metal sponges. A
      critical perspective on this emerging strategy is also provided. 

PMID- 24458847
TI  - Activation of latent TGFbeta by alphavbeta 1 integrin: of potential importance in
      myofibroblast activation in fibrosis.
AB  - Cell-mediated activation of latent TGF-beta1 is intimately involved with tissue
      repair and fibrosis in all organs. Previously, it was shown that the integrin
      beta1 subunit was required for activation of latent TGF-beta1 and skin fibrosis.
      A recent study by Henderson and colleagues (Nature Medicine 19,1617-1624, 2013)
      used three different in vivo models of fibrosis to show that integrin alphav
      subunit was required for fibrogenesis. Through a process of elimination, the
      authors conclude that in vivo, the little-studied alphavbeta1 could be the major
      integrin responsible for TGF-beta activation by myofibroblasts. Thus targeting
      this integrin might be a useful therapy for fibrosis. 

PMID- 24458845
TI  - Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation
      carriers.
AB  - It is not clear if early oral contraceptive use increases the risk of breast
      cancer among young women with a breast cancer susceptibility gene 1 (BRCA1)
      mutation. Given the benefit of oral contraceptives for the prevention of ovarian
      cancer, estimating age-specific risk ratios for oral contraceptive use and breast
      cancer is important. We conducted a case-control study of 2,492 matched pairs of
      women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected
      controls were matched on year of birth and country of residence. Detailed
      information about oral contraceptive use was collected from a routinely
      administered questionnaire. Conditional logistic regression was used to estimate
      the odds ratios (OR) and 95 % confidence intervals (CI) for the association
      between oral contraceptive and breast cancer, by age at first use and by age at
      diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was
      significantly associated with an increased risk of breast cancer for women who
      started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and
      possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06).
      The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 %
      CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 %
      with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95
      % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at
      or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive
      use before age 25 increases the risk of early-onset breast cancer among women
      with a BRCA1 mutation and the risk increases with duration of use. Caution should
      be taken when advising women with a BRCA1 mutation to take an oral contraceptive
      prior to age 25.

PMID- 24458848
TI  - Hematological parameters in relation to age, sex and biochemical values for mute
      swans (Cygnus olor).
AB  - The knowledge of the correct morphological and biochemical parameters in mute
      swans is an important indicator of their health status, body condition,
      adaptation to habitat and useful diagnostic tools in veterinary practice and
      ecological research. The aim of the study was to obtain hematological parameters
      in relation to age, sex and serum biochemistry values in wild-living mute swans.
      We found the significant differences in the erythrocyte count, hematocrit,
      hemoglobin concentration and erythrocyte sedimentation rate in relation to age of
      mute swans. There were no differences in hematological values between males and
      females. The leukogram and H/L ratio did not vary by age and sex in swans. Among
      of biochemical parameters the slightly increased AST, ALP, CK, K, urea, decreased
      CHOL and TG values were recorded. As far as we know, this is the first study in
      which the morphometric parameters of blood cells in mute swans were presented. We
      found extremely low concentration of lead in blood (at subthreshold level). No
      blood parasites were found in blood smears. The analysis of body mass and
      biometric parameters revealed a significant differences dependent on age and sex.
      No differences in the scaled mass index were found. Our results represent a
      normal hematologic and blood chemistry values and age-sex related changes, as
      reference values for the mute swan.

PMID- 24458849
TI  - Platelet rich plasma: a valid augmentation for cartilage scaffolds? A systematic
      review.
AB  - It has been shown that modern regenerative scaffold-based procedures for the
      treatment of articular cartilage defects offer good clinical results, although
      the properties of native healthy cartilage have not yet been matched by any
      substitute. Several implants have been tested and clinically used over the years
      to promote articular surface restoration, some of them producing a hyaline-like
      reparative tissue. There has been an increase in the number of new biological
      strategies, alone and in combination with scaffolds, to enhance the clinical
      outcome in patients with chondral disease. Among these innovative methods, one of
      the most widely used is Platelet-rich Plasma (PRP), based on the rationale of
      using the growth factors contained in platelet alpha granules to promote tissue
      regeneration. The aim of the present manuscript is to review systematically the
      current evidence in pre-clinical and clinical studies for the use of PRP
      augmented scaffolds to treat chondral or osteochondral disorders.

PMID- 24458850
TI  - Medication overuse headache - a complex neurologic disorder: genetic
      susceptibility deserves to be studied.

PMID- 24458851
TI  - Tryptophan hydroxylase 2 gene polymorphisms in Japanese patients with medication
      overuse headaches.
AB  - PURPOSE: We investigated whether tryptophan hydroxylase 2 (TPH2) gene
      polymorphisms were involved in the aggravation of migraines due to the overuse of
      medication. METHODS: Forty-seven migraine patients (6 males and 41 females; 36.4
      10.3 years) and 22 MOH patients (1 male and 21 females; 39.6 9.9 years) who had
      migraines participated in this study. The genotypes for the TPH2 gene
      polymorphisms (rs4565946, rs4570625, and rs4341581) were analyzed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
      RESULTS: The rs4565946, rs4570625, and rs4341581 genotypes were similarly
      distributed between migraine patients and MOH patients. CONCLUSION: The results
      of this study showed no association between tryptophan TPH2 gene polymorphisms
      and the complication of MOH in patients with migraines.

PMID- 24458852
TI  - Improvement of diagnostic rate of carpal tunnel syndrome with additional median
      to-ulnar comparative nerve conduction studies.
AB  - PURPOSE: The aim of this study is to assess whether additional median -to-ulnar
      comparative tests will improve the diagnostic rate of carpal tunnel syndrome
      (CTS). METHODS: We recruited 248 hands of 162 CTS patients, and 166 hands of 83
      controls. One hundred and sixty-eight (68%) symptomatic hands had abnormal median
      distal latencies or palm-wrist latencies. We performed three additional
      comparative tests in the remaining symptomatic hands and the non-CTS hands. The
      first test compared median distal motor latency (MDL) recorded from the second
      lumbrical muscle (2L) and ulnar distal latency recorded from interossei muscles
      (INT) (2L-INT). The second test compared median and ulnar antidromic sensory
      latencies (MS-US). And the third test compared median and ulnar nerve latencies
      in the palm-to-wrist segment (PM-PU). RESULTS: In control subjects, upper limits
      of median-to-ulnar differences were: 2L-INT= 0.4 ms, MS-US= 0.5 ms, PM-PU= 0.4
      ms. In CTS patients with normal conventional electrodiagnostic methods, MS-US
      difference showed the lowest sensitivity (21.3%). The diagnostic sensitivity of
      2L-INT was 27.5% and PM-PU 47.5%. With PM-PU test, additional 15.3% diagnostic
      rate could be got. CONCLUSION: For CTS patients with normal results from the
      standard methods, PM-PU is a good additional comparative test to further improve
      diagnostic rate.

PMID- 24458853
TI  - Moyamoya disease in an extremely old patient.
AB  - PURPOSE: The oldest patients diagnosed with moyamoya disease (MMD) in the USA may
      have been as old as 85+ years, and 68 years in Taiwan; therefore, MMD is
      generally thought not to occur in extremely old patients in Taiwan. Herein, we
      report this case to revise the common thinking. CASE REPORT: An 82-year-old woman
      had suffered twice from a right cerebral infarction. A digital subtraction
      angiogram demonstrated abundant collateral arterial networks from the bilateral
      proximal middle cerebral arteries despite the absence of arteriosclerotic
      stenosis of the bilateral extracranial internal carotid arteries. Aspirin has
      effectively controlled her symptom since diagnosis and, as a result, a direct or
      indirect revascularization procedure is unnecessary. CONCLUSION: MMD does occur
      in extremely old Taiwanese, as old as over 80 years old, and thus should be a
      differential diagnosis of cerebral infarction in an extremely old patient.
      Digital subtraction angiography is the gold standard for the diagnosis.

PMID- 24458854
TI  - A case of dermatomyositis with secondary Sjogren's Syndrome-diagnosis with follow
      up study of technetium-99m pyrophosphate scintigraphy.
AB  - PURPOSE: To report a case of dermatomyositis (DM) with secondary Sjogren's
      syndrome (SS) and propose the clinical application of technetium-99m
      pyrophosphate ((99m)Tc-PYP) scan. CASE REPORT: A 50-year-old woman had
      progressive proximal muscle weakness of bilateral thighs, myalgia, tea-colored
      urine, and exercise intolerance for 6 months. Physical examination showed malar
      rash, V-sign, periungual erythema, and mechanic hands. Neurological assessment
      showed symmetric pelvic-girdle weakness, myopathic face, waddling gait, but
      preserved deep tendon reflex and sensory functions. DM was diagnosed on the basis
      of typical rashes and serum creatinine kinase elevation (7397 IU/L). Aside from
      myopathic symptoms, dry eye and mouth were reported. Thorough autoantibody
      searches showed positive anti-SSA/Ro antibody (198 U/ml). Both Schirmer's test
      and sialoscintigraphy were positive, leading secondary SS as diagnosis. Initial
      (99m)Tc-PYP scan revealed increased radiouptake in the muscles of bilateral
      thighs, compatible with clinical assessment. Followup scan three months later
      shows abnormal but attenuated radiouptake at bilateral thighs, in the presence of
      nearly-complete clinical recovery. CONCLUSION: DM with secondary SS in adult is a
      unique disease entity, with predominantly myopathic symptoms and satisfactory
      therapeutic response as its characteristics. Our serial muscle imaging studies
      suggest that (99m)Tc-PYP scan is at once anatomically-specific and persistently
      sensitive to microstructural damages within inflammatory muscles, enabling
      clinician to monitor disease activity and therapeutic response.

PMID- 24458855
TI  - A possible case of acute disseminated encephalomyelitis after Japanese
      encephalitis.
AB  - PURPOSE: Acute disseminated encephalomyelitis (ADEM) is a monophasic
      demyelination disease of central nervous system (CNS) with presentations of
      impaired consciousness, neurologic deficits and diffuse white matter lesions on
      magnetic resonance imaging (MRI). Predisposing infection can be identified in
      around 50 to 77% of all patients with ADEM. Post-infectious autoimmune events
      associated with Japanese encephalitis have been limited to case reports of
      Guillain-Barre syndrome after Japanese encephalitis and Japanese encephalitis
      virus vaccine-related ADEM. We herein report the first possible patient with
      Japanese encephalitis developed a subsequent ADEM after recovery from Japanese
      encephalitis. CASE REPORT: A 50-year-old man suffered from an acute onset of
      headache, fever, and disturbance of consciousness. Japanese encephalitis was
      diagnosed by virological and image study. He recovered gradually and was
      discharged about 1.5 months later. However, another episode of consciousness
      impairment with violent behavior occurred 21 days after discharge. Acute
      disseminated encephalomyelitis was confirmed by brain MRI which showed newly
      developed diffuse white matter lesions. His clinical symptoms and abnormal brain
      lesions on MRI improved gradually after combination of high-dose intravenous
      methylprednisolone and oral steroid therapy. CONCLUSION: Our patient is a
      possible case of ADEM developing after Japanese encephalitis. High dose steroid
      therapy resulted in good outcome of ADEM.

PMID- 24458856
TI  - Short-lived middle cerebral artery stenosis and crime atheroma.
AB  - PURPOSE: Even after comprehensive evaluations, the etiology of 25-39% ischemic
      stroke remains unknown, and such a stroke often labeled as cryptogenic. Herein,
      we report a young patient with "cryptogenic stroke" caused by an intracranial
      atheroma, which was only visible on high-resolution magnetic resonance imaging
      (HR-MRI). CASE REPORT: A 22-year-old male presented with acute right limb
      weakness. He was a smoker and had been in good health without hypertension,
      diabetes, hyperlipidemia or cardiac diseases. Diffusionweighted imaging revealed
      ischemic lesions at left basal ganglia and left centrum semiovale. Magnetic
      resonance angiography (MRA) showed left middle cerebral artery (MCA) stenosis
      (>50%). Six days later, this stenosis disappeared on repeated MRA and digital
      subtraction angiography. HRMRI suggested a superior-wall atheroma at the location
      where the stenosis previously existed. We hypothesize heavy thrombosis formation
      at the surface of atheroma may have caused a stenosis, while the subsequent
      spontaneous fibrinolysis may gradually eliminate this thrombosis and make the
      stenosis invisible. CONCLUSION: Intracranial non-stenotic atheroma is a potential
      cause of a stroke. Our observation support HR-MRI as a tool for the etiology
      evaluation in young patients with cryptogenic stroke.

PMID- 24458857
TI  - Vertical gaze palsies from unilateral thalamic infarction.

PMID- 24458858
TI  - Periventricular heterotopia.

PMID- 24458859
TI  - Letter to the Editor re: Diagnostic accuracy of digital breast tomosynthesis
      versus digital mammography for benign and malignant lesions in breasts: a meta
      analysis.

PMID- 24458860
TI  - The lateral transport of IAA in intact coleoptiles of Avena sativa L. and Zea
      mays L. during geotropic stimulation.
AB  - Movement of IAA was studied in excised coleoptile apices and whole seedlings of
      Zea mays L. and Avena sativa L. during geotropic stimulation. A micropipette
      technique permitted the application of [5-(3)H]IAA at predetermined points on the
      coleoptiles with minimal tissue damage.When [5-(3)H]IAA was applied to the upper
      side of a horizontal excised Zea coleoptile, about 60% of the recoverable
      radioactivity had moved into the lower half after 2 h. In contrast, when
      application was made to the lower side of a horizontal excised coleoptile, only
      4% of the radioactivity migrated to the upper half. There was, thus, a net
      downward movement of 56%. Similar patterns of distribution were found for
      radioactivity in both the tissue and the basal receiver blocks. In horizontal
      shoot tissues of intact Zea seedlings a net downward movement of about 30% of the
      recoverable radioactivity occurred after 1 h of geotropic stimulation. Comparable
      experiments with Avena indicated a net downward movement of 6-12% in excised
      apices of coleoptiles and in the intact shoot. In both Zea and Avena
      chromatographic analyses of tissue and receiver blocks indicated that the
      movement of radioactivity reflected that of IAA.In Zea coleoptiles, the lateral
      migration of radioactivity after 2 h was 3 to 4 times greater in the apical
      tissues than in the basal tissues. A significant net downward movement of
      radioactivity was detected after 10 min of geotropic stimulation in the extreme
      apex of Zea coleoptiles but not in the more basal regions.These experiments show
      that downward lateral transport of IAA occurs in intact shoots of Zea and Avena
      seedlings upon geotropic stimulation. Lateral transport of IAA had previously
      been demonstrated only in sub-apical segments of Zea coleoptiles. 

PMID- 24458861
TI  - Relationship between leaf development and primary photosynthetic products in the
      C4 plant Portulaca oleracea L.
AB  - The photosynthetic products of Portulaca oleracea differ greatly depending on
      leaf age and length of exposure to (14)CO2. Mature leaves of P. oleracea fix
      (14)CO2 primarily into organic and amino acids during a 10-s exposure period.
      Less than 2% of the (14)CO2 fixed appears in phosphorylated compounds. In
      contrast, incorporation into amino acids can account for over 60% of the total
      (14)CO2 fixed by young leaves in an equal time period, and incorporation into
      alanine alone can account for up to one half of this amount. Senescent leaves
      display a quantitative shift of primary products toward phosphorylated compounds
      with a concomitant reduction of the label residing in malate and asparate. About
      8 times more phosphoglyceric acid is produced in senescent leaves than in mature
      leaves. The aspartate/ malate ratio is not constant and depends on the length of
      time the leaves are exposed to (14)CO2 and the age of the leaves under study. It
      appears as if the stage of leaf development is one of the most important factors
      determining the operation of a particular enzyme system in C4 plants. 

PMID- 24458862
TI  - Chloroplast replication in synchronously dividing Euglena gracilis.
AB  - Chloroplast replication was studied in Euglena gracilis Klebs, strain Z,
      synchronized by appropriate light-dark cycles. The chloroplasts divide
      synchronously, at the time of cytokinesis, but with a tighter synchrony than cell
      division itself. The chloroplasts within one cell are not noticeably better
      synchronized than those in the whole population. Chloroplast replication and cell
      division could not be separated by resetting the time of the light-dark cycle
      which induces the synchrony. These results are discussed for their implications
      concerning the mechanisms of integrating cell and plastid division. 

PMID- 24458863
TI  - Effects of hydroxyproline on the growth and cell-wall protein metabolism of
      excised root segments of Pisum sativum.
AB  - Hydroxyproline, in the presence of sucrose, enhanced the extension growth of
      excised 2-4 mm pea root segments in aseptic media. About 90% of protein-bound
      hydroxyproline in the pea root segments was confined to the cell-wall fraction
      where it occurred as trans-4-hydroxy-L-proline. The amounts of wall-bound
      hydroxyproline increased dramatically towards the cessation of extension growth,
      but when the segments were cultured in trans-hydroxyproline, this increase was
      considerably less.Externally supplied cis and trans-hydroxyproline inhibited the
      formation of protein-bound [(14)C]hydroxyproline from [(14)C]proline without
      affecting the total amount of [(14)C]proline incorporated into proteins. Studies
      with alphaalpha'-dipyridyl showed that, although some of the externally supplied
      trans-[(14)C]hydroxyproline was incorporated directly into cell-wall proteins,
      most of it was first converted into proline which was then incorporated into
      proteins and subsequently reconverted, in part, into hydroxyproline. The effect
      of externally supplied hydroxyproline is discussed in relation to protein-bound
      proline hydroxylation. 

PMID- 24458864
TI  - [The effect of FdUrd on nucleic acid metabolism of cells in isolated tissue
      fragments from the thallus of Riella helicophylla].
AB  - In isolated thallus fragments of Riella dedifferentiation of mature cells takes
      place in a polar region. RNA-synthesis is stimulated first and then DNA-synthesis
      as well as nuclear and cell divisions in some of the cells. DNA-synthesis is
      blocked by 10(-5) M FdUrd while polarity of dedifferentiation disappears due to
      activation of RNA-synthesis in an increasing number of cells.The influence of
      FdUrd on RNA-synthesis in regenerating fragments has been investigated by
      determining incorporation of [(14)C8]adenine-sulfate into nucleic acids and
      measuring the rate of turn-over of the latter. The nucleic acids were
      fractionated on columns of Sephadex G-150 and G-200 and subjected to
      electrophoresis on polyacrylamide gels.No differences in the rate of synthesis of
      the single species of RNA were found. Apparently, the synthetic capacity of the
      whole fragment is unchanged after treatment with FdUrd but the intercellular
      correlations which control the formation of meristematic centres are not
      evolved.After precipitation of the nucleic acids with ethanol the low molecular
      weight precursors in the supernatant were fractionated on Sephadex G-10 columns.
      After treatment with FdUrd the fraction of nucleotides has a higher rate of
      incorporation of [(14)C]adenine and a higher turn-over. It is assumed that the
      energy metabolism is changed when the cells are blocked at the beginning of the S
      phase. 

PMID- 24458865
TI  - [Transport of [(14)C] auxin from young pods of Vicia faba L].
AB  - After the injection of [(14)C]indole acetic acid (IAA) into very young pods of
      broad-bean (Vicia faba L.) the movement of the (14)C in the peduncle and stem was
      followed by autoradiography. In samples with only one young pod the basipetal
      transport was always clearly dominant. Most of the radioactivity was found in the
      bundles, particularly in the outer region of the bundle and also in the inner
      region (protoxylem parenchyma). The progression of the tracer was relatively
      complex. The rate of movement of the radioactive "front" could be as much as 2
      cm.h(-1) but most of the (14)C moved towards the base at rates clearly less than
      that of the "front". Chromatograms with several solvent systems showed that IAA
      was the main or the only mobile radioactive substance. During transport, a part
      of IAA was converted into indole-3-aldehyde (IAld) and indole-3-acetyl-aspartic
      acid (IAAsp). IAAsp and possibly also IAld, which were found mainly near the
      donor pod, seemed immobile. This work is part of a study on the interchange of
      phytohormones between fruit and plant. 

PMID- 24458866
TI  - [Active and inactive phosphate uptake in leaf cells of Elodea densa at high
      external phosphate concentrations].
AB  - The phosphate uptake in the leaf cells of Elodea densa shows multiple isotherms
      in the range [S]>1 mmole P/l to 100 mmoles P/l. In the dark the uptake isotherms
      contain three distinct parts (II/1, II/2 and II/3); the first two obey Michaelis
      Menten kinetics, whereas the third is exponential. In the light the phosphate
      uptake curve consists only of two parts (II/1 and II/2) agreeing with Michaelis
      Menten kinetics, the exponential part being absent.Cellular phosphate content was
      found to be 45 mmoles/l. Data concerning the membrane potential E for Elodea
      densa were obtained from Jeschke (1970). In accordance with the Nernst equation a
      change from the hyperbolic curve to an exponential one was expected at a
      concentration of about 60 mmoles P/l in the dark and at above 100 mmoles P/l in
      the light. The results obtained agree with these theoretical calculations: in the
      dark, the change from the hyperbolic to the exponential curve was observed at
      [S]=50 mmoles P/l, which is in electro-chemical equilibrium with the cellular
      orthophosphate content of about 35 mmoles/l (inorganic P content amounting to 80
      per cent of total phosphate). In the light no change towards an exponential curve
      was noticed.The effect of the uncoupler CCCP in the light and in the dark was
      examined in order to elucidate its influenc on (32)P incorporation into the
      fractions of inorganic, organic and acid-insoluble phosphates, the inorganic
      fraction representing phosphate uptake. The inhibition of the uptake into the
      inorganic part decreases with an increasing inactive component of total uptake,
      while the fixation in the organic fraction is severely curtailed at all
      concentrations tested. The acid-insoluble fraction remains unaffected. 

PMID- 24458867
TI  - [Discovery of NaCl induced crassulacean acid metabolism in a second member of the
      Aizoaceae family: Carpobrotus edulis].
AB  - Carpobrotus edulis grown for 24 days in nutrient solution plus 400 mM of NaCl
      shows the typical CO2 gas exchange reactions observed in CAM plants. Control
      plants grown in nutrient solution alone exhibit CO2 gas exchange reactions
      typical for C3 plants. 

PMID- 24458869
TI  - Erratum.

PMID- 24458868
TI  - Identification and localisation of auxin in primary roots of Zea mays by mass
      spectrometry.
AB  - Roots of 3.5-day-old seedlings of Zea mays L. var. Giant White Horsetooth contain
      an extractable auxin which has been identified unequivocally as IAA. A mass
      spectrometric technique has been used to determine quantitatively the levels of
      IAA in the cortical, stelar and apical regions of the roots. The IAA is
      predominantly located in the steles. 

PMID- 24458870
TI  - Sphinganine-like biogenesis of (E)-1-nitropentadec-1-ene in termite soldiers of
      the genus Prorhinotermes.
AB  - In 1974, (E)-1-nitropentadec-1-ene, a strong lipophilic contact poison of
      soldiers of the termite genus Prorhinotermes, was the first-described insect
      produced nitro compound. However, its biosynthesis remained unknown. In the
      present study, we tested the hypothesis that (E)-1-nitropentadec-1-ene
      biosynthesis originates with condensation of amino acids with tetradecanoic acid.
      By using in vivo experiments with radiolabeled and deuterium-labeled putative
      precursors, we show that (E)-1-nitropentadec-1-ene is synthesized by the soldiers
      from glycine or L-serine and tetradecanoic acid. We propose and discuss three
      possible biosynthetic pathways. 

PMID- 24458871
TI  - Decreased generation of procoagulant platelets detected by flow cytometric
      analysis in patients with bleeding diathesis.
AB  - Background: A clinically relevant bleeding diathesis is a frequent diagnostic
      challenge, which sometimes remains unexplained despite extensive investigations.
      The aim of our work was to evaluate the diagnostic utility of functional platelet
      testing by flow cytometry in this context. Methods: In case of negative results
      after standard laboratory work-up, flow cytometric analysis (FCA) of platelet
      function was done. We performed analysis of surface glycoproteins (GP) Ibalpha,
      IIb, IIIa; P-selectin expression and PAC-1 binding after graded doses of ADP,
      collagen and thrombin; content/secretion of dense granules; ability to generate
      procoagulant platelets. Results: Out of 437 patients investigated with standard
      tests between January 2007 and December 2011, we identified 67 (15.3%) with high
      bleeding scores and non-diagnostic standard laboratory work-up including platelet
      aggregation studies. Among these patients FCA revealed some potentially causative
      platelet defects: decreased dense-granule content/secretion (n=13); decreased
      alpha-granule secretion induced by ADP (n=10), convulxin (n=4) or thrombin (n=3);
      decreased fibrinogen-receptor activation induced by ADP (n=11), convulxin (n=11)
      or thrombin (n=8); decreased generation of COAT-platelets, i.e. highly
      procoagulant platelets induced by simultaneous activation with collagen and
      thrombin (n=16). Conclusion: Our work confirms that storage pool defects are
      frequent in patients with a bleeding diathesis and normal coagulation and
      platelet aggregations studies. Additionally, flow cytometric analysis is able to
      identify discrete platelet activation defects. In particular, we show for the
      first time that a relevant proportion of these patients has an isolated impaired
      ability to generate COAT-platelets - a conceptually new defect in platelet
      procoagulant activity, that is missed by conventional laboratory work-up. (c)
      2014 Clinical Cytometry Society.

PMID- 24458873
TI  - Relationships between epistaxis, migraines, and triggers in hereditary
      hemorrhagic telangiectasia.
AB  - OBJECTIVES/HYPOTHESIS: To identify whether relationships exist between epistaxis
      and migraines in hereditary hemorrhagic telangiectasia (HHT), to potentially
      provide further preventative and therapeutic options for the debilitating
      nosebleeds that are often very difficult to manage in clinical practice. STUDY
      DESIGN: Study participants were recruited from a UK specialist service, and
      online following advertisement by the HHT Foundation International. They
      completed a nonbiased questionnaire in which paired questions on nosebleeds and
      migraines were separated by at least 17 other questions. METHODS: Migraines were
      defined as headaches with associated autonomic and/or neurological features. The
      reported frequencies and precipitants of epistaxis and migraines were compared
      using numerical scales applied equally for each condition. RESULTS: The 220 HHT
      affected respondents reported frequent nosebleeds, 153 (69.5%) used iron tablets,
      and 39 (17.7%) had received at least 10 blood transfusions. Migraines displaying
      typical features were reported by 51 (23.2%), and were more common with pulmonary
      or cerebral arteriovenous malformations. Thirty of 51 (58.8%) migraine sufferers
      reported that nosebleeds occurred at the same time as their migraines. More
      frequent migraines were reported by patients with more frequent nosebleeds
      (r2=15%, P=.007), or transfusions (r2=16.9%, P=.004). In menstrual, lifestyle,
      and dietary analyses, consistency was observed between factors having no effect,
      and those provoking both nosebleeds and migraines in multiple patients
      (premenses; activity; lack of sleep; stress; caffeine, cheese, alcohol, and
      chocolate). CONCLUSIONS: We demonstrate an unexpected and provocative association
      between nosebleeds and migraines in HHT patients. Evaluation of whether
      antimigraine approaches limit HHT nosebleeds may be appropriate. LEVEL OF
      EVIDENCE: 4.

PMID- 24458872
TI  - Madecassoside ameliorates bleomycin-induced pulmonary fibrosis in mice by
      downregulating collagen deposition.
AB  - This study aimed to explore the protective effects of madecassoside (Mad), a
      triterpenoid saponin isolated from Centella asiatica herbs, on experimental
      pulmonary fibrosis (PF) and underlying mechanisms. PF model was established in
      mice by endotracheal instillation with bleomycin (5 mg/kg). Mice were orally
      administered with Mad (10, 20, 40 mg/kg) and prednisone (5 mg/kg) for 7 or 21
      days. Mad (20, 40 mg/kg) significantly improved lung pathological changes and
      reduced collagen deposition. In the aspect of collagen synthesis, Mad (20, 40
      mg/kg) reduced the expressions of alpha-smooth muscle actin and transforming
      growth factor-beta1 (TGF-beta1), and inhibited the phosphorylations of Smad2 and
      Smad3 in the lung tissues. However, in vitro, Mad showed little effect on TGF
      beta1-induced phosphorylation of either Smad2 or Smad3 in primary mouse lung
      fibroblasts. Moreover, Mad (20, 40 mg/kg) attenuated oxidative damage and
      inflammation presented at the early stage of PF, evidenced by reduced total
      leukocytes in the bronchoalveolar lavage fluid, decreased myeloperoxidase
      activity and malondialdehyde level, and increased super-oxide dismutase activity
      and glutathione level in lung tissues. On the other hand, Mad (40 mg/kg) elevated
      the matrix metalloproteinase 1/tissue inhibitor of metalloproteinase 1 ratio in
      lung tissues of PF mice mainly by downregulating tissue inhibitor of
      metalloproteinase 1 expression. The present study demonstrated that Mad can
      ameliorate PF by preventing the deposition of extracellular matrix, which might
      be achieved mainly through attenuating inflammation and oxidative stress and
      consequent TGF-beta1 overexpression.

PMID- 24458874
TI  - Tricho-odonto-onycho-dermal dysplasia and WNT10A mutations.
AB  - We report on three novel (IVS2+1G>A splice site, c.1066G>T, and c.1039G>T, and
      one previously reported (c.637G>A) WNT10A mutations in three patients affected
      with odonto-onycho-dermal dysplasia (OODD; OMIM 275980). OODD is a rare form of
      autosomal recessive ectodermal dysplasia involving hair, teeth, nails, and skin,
      characterized by hypodontia (tooth agenesis), smooth tongue with marked reduction
      of filiform and fungiform papillae, nail dysplasia, dry skin, palmoplantar
      keratoderma, and hyperhidrosis of palms and soles. The novel IVS+1G>A splice site
      mutation is predicted to cause significant protein alteration. The other novel
      mutations we found including c.1066G>T and c.1039G>T are predicted to cause
      p.Gly356Cys and p.Glu347X, respectively. Barrel-shaped mandibular incisors and
      severe hypodontia appear to be associated with homozygous or compound
      heterozygous mutations of WNT10A. The name "tricho-odonto-onycho-dermal
      dysplasia" is suggested to replace "odonto-onycho-dermal dysplasia" because hair
      anomalies including hypotrichosis and slow-growing hair have been reported in
      numerous reported patients with this syndrome.

PMID- 24458875
TI  - Body fat, especially visceral fat, is associated with electrocardiographic
      measures of sympathetic activation.
AB  - OBJECTIVE: Obesity is associated with sympathetic activation, but the role of
      different fat depots is unclear. The association between body fat, specifically
      visceral fat, and electrocardiographic measures of sympathetic activation in a
      population with structurally normal hearts was investigated. METHODS: In this
      cross-sectional baseline analysis of the Netherlands Epidemiology of Obesity
      study, body fat percentage was assessed with BIA and abdominal subcutaneous (SAT)
      and visceral adipose tissue (VAT) with magnetic resonance (MR) imaging. Mean
      heart rate (HR) and five other electrocardiographic measures of sympathetic
      activation were calculated. We performed multivariate linear regression analyses.
      RESULTS: In 868 participants with a mean age(SD) of 55(6) years, BMI of 26(4)
      kg/m(2) , 47% men, body fat was associated with HR and two other measures of
      sympathetic activation. Per sex-specific SD total body fat, the difference in HR
      was 1.9 beats/min (95% CI: 1.0, 2.9; P < 0.001) and per SD waist circumference
      2.1 beats/min (95% CI: 1.3, 2.9; P < 0.001). The difference in HR per SD VAT was
      2.1 beats/min (95% CI: 1.3, 3.0; P < 0.001). CONCLUSIONS: Body fat, especially
      visceral fat, was associated with electrocardiographic measures of sympathetic
      activation. Our study implies that already before the onset of cardiovascular
      disease, excess (visceral) body fat is associated with sympathetic activation.

PMID- 24458876
TI  - Detection of tetrodotoxin-producing Providencia rettgeri T892 in Lagocephalus
      pufferfish.
AB  - Tetrodotoxin (TTX) is a potent toxin but it could be used in pharmaceutical
      field. Identification of TTX producing bacteria in pufferfish is necessary for
      TTX yield and the pufferfish conservation. In this study, Lagocephalus was
      collected from Cam Ranh Sea, a central part of Vietnam during spring season. The
      liver and intestine were incubated in 0.9 % NaCl for TTX detection in pufferfish.
      To be benefited from the isolation of new TTX producing bacteria, the liver and
      intestine were incubated in 6.5 % NaCl. The cultures were used to test the toxin
      and to isolate the bacterial community that could yield TTX. Surprisingly,
      Providencia rettgeri T892 in intestine could produce TTX identified by
      biochemical test and 16S rRNA sequencing. This strain was used to test the
      production of TTX, based on thin layer chromatography (TLC), mouse bioassay and
      high performance liquid chromatography (HPLC) analysis. The bacterium was
      optimized for TTX production in media prepared from the meat-washing water of
      Auxis thazard, Megalaspis cordyla and Decapterus maruadsi. Interestingly, the TTX
      obtained 0.106 mg/mL and 0.055 mg/mL in medium prepared from A. thazard and M.
      cordyla, respectively while there was no TTX production detected in medium
      prepared from D. maruadsi. This paper could contribute to warn to the human
      health care system about a possible TTX poisoning in some cases related to eating
      fishes. 

PMID- 24458877
TI  - Improvement of catalytic efficiency and thermostability of recombinant
      Streptomyces griseus trypsin by introducing artificial peptide.
AB  - Streptomyces trypsin is one of the serine proteinases in Streptomyces griseus and
      acts as a key mediator during cell growth and differentiation. S. griseus trypsin
      (SGT) could be successfully expressed in Pichia pastoris by engineering the
      natural propeptide APNP. In this study, the recombinant Exmt with peptide YVEF
      and the wild-type SGT were comparatively investigated in detail. The recombinant
      Exmt showed significantly increased thermostability which t(1/2) value was 3.89
      fold of that of the SGT at 40  degrees C. Moreover, the catalytic efficiency
      (referring to the specificity constant, k cat/K m) and pH tolerance of Exmt were
      also improved. In silico modeling analysis uncovered that introduction of the
      peptide YVEF resulted in a broadened substrate binding pocket and closer
      catalytic triad (His57, Asp102 and Ser195). The intramolecular Hydrogen bonds and
      the cation pi-interactions were also dramatically increased. The results
      indicated that engineering of the N-terminus with artificial peptides might be an
      effective approach for optimizing the properties of the target enzymes.

PMID- 24458878
TI  - Onset of action of the beta3-adrenoceptor agonist, mirabegron, in Phase II and
      III clinical trials in patients with overactive bladder.
AB  - PURPOSE: Long-term persistence with pharmacotherapy for overactive bladder (OAB)
      requires a drug with an early onset of action and good efficacy and tolerability
      profile. Although antimuscarinics improve OAB symptoms within 1-2 weeks of
      initiating treatment, adherence after 3 months is relatively poor due to
      bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a beta3
      adrenoceptor agonist, has demonstrated significant improvements in key symptoms
      of OAB and good tolerability after 12 weeks in Phase III studies. METHODS: This
      was a prespecified pooled analysis of three randomized, double-blind, placebo
      controlled, 12-week studies, and a Phase II study, to evaluate efficacy and
      tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy
      endpoints were change from baseline to week 1 (Phase II only), week 4, and final
      visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean
      volume voided/micturition (MVV). RESULTS: A significant benefit for mirabegron 25
      and 50 mg versus placebo was evident at the first assessment point, 4 weeks after
      initiation of therapy, in Phase III studies for incontinence, micturitions, and
      MVV. The earliest measured benefit was after 1 week, in the Phase II study.
      Quality-of-life parameters also significantly improved with mirabegron 25 and 50
      mg as early as week 4. Significant benefits continued throughout the studies.
      Mirabegron was well tolerated. CONCLUSIONS: The early onset of action and good
      overall efficacy and tolerability balance that mirabegron offers may lead to high
      rates of persistence with mirabegron in the long-term treatment of OAB.

PMID- 24458879
TI  - Real-life experience with azacitidine in myelodysplastic syndromes according to
      IPSS cytogenetic profile.

PMID- 24458881
TI  - Iron deficiency in patients with solid tumours: prevalence and management in
      clinical practice.
AB  - PURPOSE: The objective of the present study was to describe the prevalence and
      management of anaemia and iron deficiency (ID) in treatment-naive patients with
      solid tumours in Spain and the incidence of anaemia over 4 months of cancer
      treatment in clinical practice. METHODS: Multicentre, prospective and
      observational study in newly diagnosed cancer patients. Data on anaemia and iron
      parameters and its management were collected prior to the initiation of
      chemotherapy, at each cycle of chemotherapy and after 4 months of treatment. The
      main outcomes of the study were the prevalence of anaemia at baseline, its
      incidence during cancer treatment and the prevalence of absolute ID (AID) and
      functional ID (FID) prior to chemotherapy initiation. RESULTS: A total of 295
      patients were included in the study. Anaemia was present at diagnosis in 38.6 %
      of patients and was treated only in 32.5 % of those. A total of 106 patients
      (60.2 %) without anaemia at baseline developed anaemia during cancer treatment.
      Serum ferritin and transferrin saturation data were available for 151 of the
      patients (51.2 %) included in the study. The overall prevalence of ID was 59 %:
      48 patients (31.8 %) presented with AID and 41 patients (27.2 %) presented with
      FID before starting anti-cancer therapy. Thirty-three of 44 non-anaemic iron
      deficient patients did not receive any type of iron supplementation before
      initiating cancer therapy. CONCLUSIONS: Iron parameters are not commonly measured
      in newly diagnosed cancer patients. A correct evaluation and early management of
      ID could reduce the incidence of treatment-related anaemia in cancer patients.

PMID- 24458880
TI  - Tissue-based biomarkers predicting outcomes in metastatic colorectal cancer: a
      review.
AB  - Although there have been recent advances in the treatment of metastatic
      colorectal cancer, particularly with systemic chemotherapy, new biological agents
      and surgical metastasectomy, the disease remains difficult to treat. To
      personalise the management of mCRC and optimise patient outcomes, it is vital to
      acquire a deeper understanding of its natural history and mechanisms behind
      disease progression. This may be achieved by extensive study of tumour
      biomarkers: proteins or genetic alterations within neoplastic cells or their
      surrounding stroma that may be used to predict patient outcomes, disease
      trajectory and response to various therapies. The discovery of mutant Kirsten-RAS
      in determining patients who may be refractory to anti-epidermal growth factor
      receptor treatments has reinvigorated and reiterated the importance of our
      attempts to individualise cancer care. While many biomarkers have been studied
      and shown promise in the setting of mCRC, they are, with the exception of K-ras
      testing not used currently in a clinical setting due to conflicting results,
      small patient samples and methodological variations. Larger, multi-centric
      studies with uniform methods of tumour marker study are required to effectively
      tailor systemic therapies and select appropriate candidates for surgical
      metastasectomy. 

PMID- 24458882
TI  - The proteins released by isolated barley aleurone layers before and after
      gibberellic-acid treatment.
AB  - Isolated barley (Hordeum vulgare L.) aleurone layers released a number of
      proteins into an aqueous medium in the absence of gibberellic acid (GA3).
      Evidence from molecular weight determinations and a number of immunological tests
      indicated that these proteins were water-soluble endosperm proteins which
      apparently arose from endosperm cells which adhered to the layers during
      isolation. They were not aleurone-cell proteins. By means of immunofluorescence,
      the water-soluble endosperm proteins were found to be concentrated around starch
      grains in the starchy endosperm. These proteins were resistant to hydrolysis by
      GA3-induced hydrolases released from aleurone tissue.Isolated aleurone layers
      could be washed free of soluble endosperm proteins. After treatment with GA3,
      such layers released another group of proteins which were shown by immunological
      and electrophoretic methods to be uncontaminated by soluble endosperm proteins.
      The pure GA3-induced proteins were separated, using SDS-acrylamide gel disc
      electrophoresis, into 12 components which had molecular weights (monomer) from
      15500 to 81000. Ten of these protein bands became radioactive if GA3-treatment of
      layers was carried out in the presence of radioactive amino acids, and therefore
      probably contained de novo synthesized proteins. The two protein bands which were
      not labelled contributed about 40% of the protein released by washed aleurone
      layers after GA3 treatment, and their production appeared to be dependent on
      proteolysis. 

PMID- 24458883
TI  - Measurements of photorespiration in some microscopic algae.
AB  - The rate of photorespiration in three green algae and four blue-green algae was
      determined by the measurement of the rate of loss of photosynthetically fixed
      (14)CO2 in light in CO2-free air at 25 degrees . In all algae studied, CO2
      evolution in light was considerably less than that in the dark, except for
      Chlamydomonas reinhardii which released slightly more CO2 in the light. Raising
      the temperature to 35 degrees  had little effect on the ratio of light to dark
      (14)CO2 release. Blue-green algae showed the lowest photorespiration rate of the
      algae studied. 

PMID- 24458884
TI  - Auxin and ethylene control of growth in epidermal cells of Pisum sativum: A
      biphasic response to auxin.
AB  - The effects of IAA and ethylene have been compared on the development of
      epidermal cells in intact shoots of etiolated pea plants. In the expanding sub
      apical region ethylene has little effect on cell volume over 24 h but between 12
      and 24 h rapid increases occur in cell wall thickening, part of which is due to
      the deposition of longitudinally orientated microfibrils adjacent to the
      plasmalemma. During this period, there is a rise in the levels of extractable
      cytoplasmic peroxidase. Two distinct phases of growth occur in response to IAA:
      an initial stimulation of cell expansion which causes the wall to stretch and
      decrease inthickness relative to the control (this phase is considered to be the
      true auxin response), followed some 12 h later by a decline in the rate of
      expansion and a thickening of the cell walls. During the first phase, peroxidase
      levels are depressed by IAA but a stimulation occurs after prolonged treatment.
      The effects observed in the second phase are believed to be mediated by ethylene
      which is synthesized at a high rate following treatment with IAA. Epidermal cells
      of mature internodes show a slight first phase expansion in response to IAA and
      their walls become a little thinner. Ethylene, however, has no effect on either
      expansion or wall thickness of mature cells even though the activity of
      peroxidase and the level of hydroxyproline-rich protein in the wall increases.
      These findings are discussed in relation to the dual regulation of cell growth by
      auxin and ethylene and the biphasic nature of the auxin response. 

PMID- 24458885
TI  - On the specific binding of protochlorophyllide and chlorophyll to different
      peptide chains.
AB  - By means of labelling experiments with delta-[(3)H]aminolevulinic acid (ALA) and
      SDS acrylamide gel electrophoresis the following results were obtained with
      plantlets of Zea mays L.: Protochlorophyllide is associated with two peptide
      chains of the molecular weights (MW) 21000 and 29000, thus forming two
      protochlorophyllide holochromes. Chlorophyll may be associated with four peptide
      chains of MW 21000, 25000, 29000 and 70000, forming four chlorophyll holochromes.
      When plantlets are transfrrred to light, protochlorophyllide is converted to
      chlorophyll but this remains associated with the peptide chains MW 21000 and
      29000; in addition, chlorophyll is synthesized from unmetabolized ALA and
      associated with peptide chains MW 25000 and 70000. These conversions occur both
      in dark-grown plantlets and in green plantlets transferred to darkness and then
      again exposed to light, but in the latter considerably faster than in the former.
      The results suggest the existence of two pathways for the formation of
      chlorophyll holochromes, one requiring a dark period followed by light, the other
      occurring without a dark phase. Light may not only be required for
      photoconversion of protochlorophyllide to chlorophyll, but may also be involved
      in the regulation of the formation of the protein-pigment complexes. 

PMID- 24458886
TI  - Movement of radioactivity from [(3)H]GA 3 in geotropically stimulated coleoptiles
      of Zea mays.
AB  - The movement of radioactivity from [(3)H]GA3 has been studied in horizontal and
      vertical segments of Zea mays coleoptiles. No evidence was obtained for the polar
      movement of radioactivity within the segment, and no radioactivity significantly
      above background was detected in the receiver blocks. A gradient of radioactivity
      was not established between the upper and lower halves of horizontal segments
      supplied at their apical ends with a symmetrical donor block, and again no
      radioactivity was recovered in the basal receiver blocks. An enhanced lateral
      movement of radioactivity could not be detected in horizontal segments supplied
      with asymmetrical donor blocks at their apical ends. 

PMID- 24458887
TI  - A note on some non-membranous structures in plant mitochondria.
AB  - Electron-opaque inclusions, seen in the mitochondrial matrix of several plant
      tissues after glutaraldehyde and osmium tetroxide fixation, with uranyl acetate
      and lead citrate poststaining, are described. Some tentative proposals about
      their composition and function are put forward. 

PMID- 24458888
TI  - In-vitro binding of morphactins and 1-N-naphthylphthalamic acid in corn
      coleoptiles and their effects on auxin transport.
AB  - Utilizing the specific binding of radioactive 1-N-naphthylphthalamic acid (NPA)
      to a particulate fraction of corn coleoptiles, a series of NPA and morphactin
      analogues were tested for competition with the NPA binding site. Competition for
      this binding site was found for NPA itself, chloro-1-N-naphthylphthalamic acid
      and dichloro-1-N-naphthylphthalamic acid, to about the same degree. 1-N
      phenylphthalamic acid and 4-chloro-1-N-phenylphthalamic acid were less active,
      and 1-N-naphthylphthalimide did not compete for the NPA binding site Morphactins
      were found to compete for the NPA site as well; the free fluorenol acids, 2
      chloro-9-hydroxylflorene-9-carboxylate and 9-hydroxyfluorene-9-carboxylate,
      compete better for the NPA binding site than n-butyl-9-hydroxyfluorene-9
      carboxylate (Bu-HFC), methyl-2-chloro-9-hydroxyfluorene-9-carboxylate (Me-Cl-HFC)
      and methyl-2,7-dichloro-9-hydroxyfluorene-9-carboxylate (Me-diCl-HFC). The
      inhibition of NPA binding has the characteristics of a competitive inhibition
      when examined in double-reciprocal plots.The transport of auxin (indolyl-3-acetic
      acid, IAA) is inhibited by both NPA and fluorenol derivatives but whilst the free
      acids have superior binding activity, transport is more effectively inhibited by
      the fluorenol esters including Bu-HFC, Me-Cl-HFC and Me-diCl-HFC than by the free
      fluorenol acids. It is probable that the free fluorenol acids are the active form
      for inhibition of IAA transport and that the fluorenol esters undergo hydrolysis
      before acting on IAA transport. 

PMID- 24458889
TI  - [Antibodies against glyoxysomal membranes].
AB  - Antibodies against glyoxysomes were prepared by injection of purified glyoxysomal
      membranes from watermelon cotyledons (day 3) into rabbits and isolation of the
      gammaglobulin fraction from the antiserum by ammonium sulfate fractionation.
      Double gel diffusion as well as two-dimensional immunoelectrophoresis (tandem
      technique, Fig. 4) tests using the purified antiserum and glyoxysomes or crude
      cotyledon extracts gave a single converging immunoprecipitation band. The antigen
      concentrations at different developmental stages were determined by one
      dimensional immunoelectrophoresis (Fig. 5). Cotyledons of dry seeds contain low
      but measurable amounts of antigen. After day 2 there is a fast increase and after
      day 3 a subsequent slow decline of antigen. Since mitochondria and endoplasmic
      reticulum also formed single identical bands with antiglyoxysoma antibodies (Fig.
      6) the results of Fig. 5 reflect the synthesis and destruction of membrane
      material belonging to several organelles.The reported experiments support the
      hypothesis of Kagawa, Lord and Beevers (1973) that components of glyoxysomal and
      mitochondrial membranes originate in a light membrane fraction derived from the
      endoplasmic reticulum. The consequences of this hypothesis in terms of organelle
      morphogenesis are discussed. 

PMID- 24458890
TI  - Haploid plants from anthers of tobacco - Enhancement with charcoal.
AB  - Haploid plants of Nicotiana tabacum L. were produced in greater numbers from
      anthers on agar medium containing activated charcoal than on the same medium
      without charcoal. 

PMID- 24458891
TI  - Healthcare utilization and costs of Veterans screened and assessed for traumatic
      brain injury.
AB  - Approximately 15% of casualties in the Afghanistan (Operation Enduring Freedom
      [OEF]) and Iraq (Operation Iraqi Freedom [OIF]) conflicts received mild traumatic
      brain injury (TBI). To identify Veterans who may benefit from treatment, the
      Department of Veterans Affairs (VA) implemented a national clinical reminder in
      2007 to screen for TBI. Veterans who screen positive are referred for a
      comprehensive TBI evaluation. We conducted a national retrospective study of
      OIF/OEF Veterans receiving care at VA facilities between 2007 and 2008. We
      examined the association of the TBI screen with healthcare costs over a 12 mo
      period following the initial evaluation. Of the Veterans, 164,438 met inclusion
      criteria: 31,627 screened positive, 118,545 screened negative, and 14,266
      received no TBI screening. Total healthcare costs of Veterans who screened
      positive, screened negative, or had no TBI screening were $9,610, $5,184, and
      $3,399, respectively (p < 0.001). Understanding these healthcare utilization and
      cost patterns will assist policymakers to address the ongoing and future
      healthcare needs of these returning Veterans. 

PMID- 24458892
TI  - Methods for characterization of mechanical and electrical prosthetic vacuum
      pumps.
AB  - Despite increasingly widespread adoption of vacuum-assisted suspension systems in
      prosthetic clinical practices, there remain gaps in the body of scientific
      knowledge guiding clinicians' choices of existing products. In this study, we
      identified important pump-performance metrics and developed techniques to
      objectively characterize the evacuation performance of prosthetic vacuum pumps.
      The sensitivity of the proposed techniques was assessed by characterizing the
      evacuation performance of two electrical (Harmony e-Pulse [Ottobock; Duderstadt,
      Germany] and LimbLogic VS [Ohio Willow Wood; Mt. Sterling, Ohio]) and three
      mechanical (Harmony P2, Harmony HD, and Harmony P3 [Ottobock]) prosthetic pumps
      in bench-top testing. Five fixed volume chambers ranging from 33 cm(3) (2 in.(3))
      to 197 cm(3) (12 in.(3)) were used to represent different air volume spaces
      between a prosthetic socket and a liner-clad residual limb. All measurements were
      obtained at a vacuum gauge pressure of 57.6 kPa (17 inHg). The proposed
      techniques demonstrated sensitivity to the different electrical and mechanical
      pumps and, to a lesser degree, to the different setting adjustments of each pump.
      The sensitivity was less pronounced for the mechanical pumps, and future
      improvements for testing of mechanical vacuum pumps were proposed. Overall, this
      study successfully offers techniques feasible as standards for assessing the
      evacuation performance of prosthetic vacuum pump devices. 

PMID- 24458893
TI  - Comparison of two impression techniques for auricular prosthesis: pilot study.
AB  - The purpose of this article was to compare the accuracy of a new impression
      technique, the triple-layer impression technique (TLIT), with the conventional
      impression technique (CIT) to fabricate an auricular prosthesis. Fifteen male
      subjects (aged 22-45 yr) were selected. Ten markings were made on the subject's
      ear (super aurale [sa], sub aurale [sba], pre aurale [pra], post aurale [poa], A,
      A1, B, B1, C, and C1) and five measurements (sa-sba, pra-poa, A-A1, B-B1, and C
      C1) were made. Custom-made trays were used to record impression in CIT and TLIT.
      Impressions were made using alginate, and models were cast with type IV gypsum
      product. Markings were transferred on the cast. Measurements were rechecked on
      the models. Distribution analysis of difference in measurements between the two
      impression techniques and the subject's actual values was evaluated. Sign test
      was used to analyze the statistical significance. Statistically significant
      differences were found in measurements A-A1, B-B1, and C-C1 between the two
      techniques when compared with the subject's actual dimensions (p < 0.01). TLIT
      was found to produce accurate models when compared with CIT. The TLIT used in the
      study was cost effective, less technique sensitive, and tailor made to reduce
      chairside orientation time during wax try-in appointments for rehabilitating
      patients, especially those with unilateral auricular defects. 

PMID- 24458894
TI  - Relationship between cognition and gait performance in older adults receiving
      physical therapy interventions in the home.
AB  - Persons undergoing physical therapy home services often have difficulty with
      mobility and gait. The purpose of this study was to determine whether there was a
      relationship between gait and a rating of cognitive functioning in persons
      undergoing home-care physical therapy services. Patients over the age of 65 (n =
      11,601) seen by a home-care agency between 2007 and 2008 were included in the
      retrospective analysis, and 10,953 (mean +/- standard deviation age 83.2 +/- 7.1;
      31%) met the criteria of being able to ambulate independently or with an
      assistive device. All patients attempted to perform the modified Clinical Test of
      Sensory Integration and Balance plus either the Performance Oriented Measurement
      Assessment (POMA) or the Dynamic Gait Index (DGI). Mental function was scored as
      part of the Outcome and Assessment Information Set. A multivariate model with
      adjustment for age and sex identified gait performance as measured by the DGI to
      be independently associated with the likelihood that a patient required cognitive
      prompting (p = 0.03). Both the DGI and POMA scores were independently associated
      with requiring assistance/dependence with cognitive tasks. There was a strong
      relationship between cognition and gait performance in persons undergoing
      physical therapy interventions in the home. Changes in gait may be related to
      cognitive decline. 

PMID- 24458895
TI  - Predictive value of upper-limb accelerometry in acute stroke with hemiparesis.
AB  - Few studies have investigated how well early activity measurements by
      accelerometers predict recovery after stroke. First, we assessed the predictive
      value of accelerometer-based measurements of upper-limb activity in patients with
      acute stroke with a hemiplegic arm. Second, we established the difference in arm
      activity between hospitalized stroke and nonstroke patients. In total, 129
      patients with acute stroke and 19 controls participated. Activity of the upper
      limbs was monitored for 48 h, and these data were used to determine the
      predictive value of the activity variables compared with the modified Rankin
      Scale (mRS), which was assessed at 3 mo poststroke onset. The sensitivity and
      specificity in relation to the mRS were 0.80 and 0.77, respectively, for the
      activity of impaired arm (AIA) and 0.85 and 0.75, respectively, for the ratio
      variable calculated by dividing the AIA by the activity of the nonimpaired arm.
      The corresponding cutoff values were 597,546 counts for AIA and 0.33 for the
      ratio. The predictive value of AIA combined with age was 85% to the disability
      status defined as an mRS score of 2 or less. 

PMID- 24458896
TI  - Sampling frequency impacts measurement of walking activity after stroke.
AB  - The purpose of this study was to examine the effect of sampling epoch on total
      time spent walking and number of walking bouts per day in persons with stroke.
      Ninety-eight persons with average age of 63.8 yr and average time poststroke of
      43.6 mo participated. Participants wore a StepWatch Activity Monitor for 3 to 5
      consecutive days. The number of strides taken was collected in consecutive 5 s
      epochs and down sampled into 10, 20, 30, and 60 s epochs. Total time walking and
      total number of walking bouts were determined for each day. Low activity days
      were defined as days below the 25th percentile of total steps per day and high
      activity days as days above the 75th percentile of total steps per day. Total
      time walking and total number of bouts were different for each sampling epoch (p
      < 0.001 for all). The 5 s sampling epoch resulted in calculation of ~40% of the
      walking time and ~6 times as many bouts as a 60 s sampling epoch. Differences
      were greater for low activity days (p < 0.001 for all). Sampling epoch affects
      daily step activity variables whose calculation depends on time, especially
      during low activity days. Sampling epoch must be carefully considered when
      designing studies aimed at understanding patterns of daily walking activity. 

PMID- 24458897
TI  - Mechanisms of arm paresis in middle cerebral artery distribution stroke: pilot
      study.
AB  - The development of effective neurobiological adjuvants to rehabilitation of
      paresis caused by stroke will depend on understanding mechanisms of paresis. Our
      objective was to determine the extent to which upper-limb (UL) paresis after
      nonlacunar ischemic middle cerebral artery (MCA) distribution stroke is caused by
      infarction of posterior periventricular white matter (PVWM), where corticospinal
      fibers serving movement descend, and caused by infarction of the arm-hand region
      of precentral gyrus (ahPCG). We conducted a blinded, retrospective analysis of
      computed tomography and magnetic resonance imaging from a convenience sample of
      64 prospectively evaluated subjects with UL paresis resulting from MCA
      distribution stroke. Of the subjects, 96.5% had PVWM involvement while 53% had
      minimal or no ahPCG involvement. Even in subjects with no UL function, 56% had
      very minimal infarction (<25%) of the ahPCG. Degree of paresis was statistically
      associated with presence or absence of detectable posterior PVWM damage but not
      with extent of ahPCG involvement. These preliminary findings suggest that
      posterior PVWM involvement may be a major, if not the principal, determinant of
      paresis in all hemispheric ischemic strokes and motivate further prospective
      studies of this problem. 

PMID- 24458898
TI  - Functionality of i-LIMB and i-LIMB pulse hands: case report.
AB  - The availability of various multiarticulated prosthetic hands makes determining
      differences in functionality between these hands relevant. The current study
      asked whether the functionality of these hands increased with time of use and
      whether grip force and robustness improved. A 45-year-old man with wrist
      disarticulation used the i-LIMB and the i-LIMB Pulse hands in a series of tests
      covering all functional levels as described in the framework of the International
      Classification of Functioning, Disability and Health. Using the i-LIMB for 1 yr
      improved Southampton Hand Assessment Procedure function scores. However, the i
      LIMB Pulse did not improve much over 5 mo of training, possibly because of the
      intense training in the month prior to the first i-LIMB Pulse tests. The i-LIMB
      Pulse hand generally showed higher scores on the tests and better grip strength
      and robustness than the i-LIMB. The i-LIMB Pulse has overcome the shortcomings of
      the i-LIMB hand. The preset grip patterns simplified the complex control of the
      multiarticulated i-LIMB hand, which contributed to patient satisfaction. 

PMID- 24458899
TI  - Biomechanical evaluation of wrist-driven flexor hinge orthosis in persons with
      spinal cord injury.
AB  - The wrist-driven flexor hinge orthosis (WDFHO) is a device used to restore hand
      function in persons with tetraplegic spinal cord injury by furnishing three-point
      prehension. We assessed the effectiveness and biomechanical properties of the
      WDFHO in 24 persons with cervical 6 or 7 tetraplegia who have severely impaired
      hand function. This study introduces a mechanical operating model to assess the
      efficiency of the WDFHO. Experimental results showed that pinch force increased
      significantly (p < 0.001) after using the WDFHO and was found to positively
      correlate with the strength of wrist extensor muscles (r = 0.41, p < 0.001).
      However, when the strength of the wrist extensors acting on the WDFHO was
      greater, the reciprocal wrist and finger motion that generates three-point
      prehension was less effective (r = 0.79, p < 0.001). Reliable and valid
      biomechanical evaluation of the WDFHO could improve our understanding of its
      biomechanics. 

PMID- 24458900
TI  - Body composition and physical function in women with multiple sclerosis.
AB  - Persons with multiple sclerosis (MS) have reduced physical activity (PA) and
      lower-limb physical function and potentially disordered body composition compared
      with their peers without MS. The aim of this study was to determine whether PA
      and body composition were differentially associated with lower-limb physical
      function in persons with MS compared with controls. Females with MS and age- and
      body mass index-matched female controls (n = 51; average age 48.1 +/- 9.7 yr)
      were measured for PA with daily step counts, relative fat mass (%Fat), and leg
      lean mass (LM-LEG) via dual energy X-ray absorptiometry and for lower-limb
      physical function with objective performance tests. Persons with MS had 12.5% to
      53% poorer lower-limb physical function than controls (all p < 0.05). PA, %Fat,
      and LM-LEG to body mass ratio (LM-LEG/BM) were associated with lower-limb
      physical function in both persons with MS and controls (all p < 0.05). Based on
      median splits, higher %Fat, lower LM-LEG/BM, and MS conferred poorer lower-limb
      physical function (all p < 0.05). PA, %Fat, and LM-LEG/BM were associated with
      lower-limb physical function, suggesting that body composition, specifically
      reducing adiposity and increasing lean mass and/or increasing PA levels, may be a
      potential target for MS interventions. 

PMID- 24458901
TI  - Effects of foot posture and heel padding devices on soft tissue deformations
      under the heel in supine position in males: MRI studies.
AB  - Heel ulcers (HUs) are the second most common pressure ulcers (PUs). Despite the
      significant morbidity and economic cost associated with HUs, there remains a lack
      of understanding of the basic pathophysiology of PUs because of limited basic
      research. There are only sparse data regarding the efficacy of prevention aids
      such as heel padding devices, and these data are based mainly on epidemiological
      research rather than biomechanical models and deformation measurements. This
      study was designed to explore the effects of foot posture and support stiffness
      properties on soft tissue deformations using magnetic resonance imaging (MRI).
      Subjects were scanned with and without weight bearing, in neutral external
      rotation position and in 90 degrees to supporting surface and with different heel
      padding devices. Tissue strains were calculated for skin, subcutaneous tissue,
      and effective (total) soft tissue. We found skin strains with the foot in
      external rotation to be significantly greater than when the foot was upright.
      Heel padding devices have a statistically significant effect on reducing the
      extent of deformations in both skin and subcutaneous tissues. Furthermore, the
      design features of heel padding devices have substantial influence on tissue
      deformations. This study demonstrates how MRI provides convenient, accurate, and
      quantitative comparison of biomechanical performances of heel padding devices. 

PMID- 24458903
TI  - Guest Editorial: Examining effects of equine-assisted activities to help combat
      veterans improve quality of life.

PMID- 24458902
TI  - Visual training and emotional state of people with retinitis pigmentosa.
AB  - The purpose of the study was to improve the visual functioning of people with
      restriction in contrast sensitivity (CS), such as retinitis pigmentosa (RP), by
      means of a visual training program. Twenty-six volunteers with RP participated,
      distributed in two groups: 15 who made up the experimental group (who received
      the training program) and 11 who participated as a control group (without
      training). Participants were evaluated before beginning training, on completion,
      and 3 mo following completion for CS with the Pelli-Robson Contrast Sensitivity
      (P&R) test, visual functioning with the Visual Function Questionnaire (VFQ), and
      in emotional state with the Beck Depression Inventory (BDI). The training program
      is based on software that generates luminous stimuli of varying duration and
      intensity and registers the stimuli perceived by the subject. The outcomes showed
      significant differences posttraining in the experimental group in depression
      (F1,14 = 5.42; p < 0.04), VFQ (Z = -2.27; p < 0.02), and P&R in the right eye (Z
      = -1.99; p < 0.046) and left eye (Z = -2.30; p < 0.02) but not in binocular (Z = 
      0.96; p < 0.34). The outcomes showed that the experimental group made significant
      progress in all variables and these effects remained after 3 mo, which suggests
      that the program could be a helpful addition to RP rehabilitation and help
      mitigate the damage. 

PMID- 24458904
TI  - Guest editorial: Overcoming barriers to care for returning veterans: expanding
      services to college campuses.

PMID- 24458908
TI  - Dispersible carbon nanotubes.
AB  - A method is proposed to produce nanoparticles dispersible and recyclable in any
      class of solvents, and the concept is illustrated with the carbon nanotubes.
      Classically, dispersions of CNTs can be achieved through steric stabilization
      induced by adsorbed or grafted polymer chains. Yet, the surface modification of
      CNTs surfaces is irreversible, and the chemical nature of the polymer chains
      imposes the range of solvents in which CNTs can be dispersed. To address this
      limitation, supramolecular bonds can be used to attach and to detach polymer
      chains from the surface of CNTs. The reversibility of supramolecular bonds offers
      an easy way to recycle CNTs as well as the possibility to disperse the same
      functional CNTs in any type of solvent, by simply adapting the chemical nature of
      the stabilizing chains to the dispersing medium. The concept of supramolecular
      functionalization can be applied to other particles, for example, silica or metal
      oxides, as well as to dispersing in polymer melts, films or coatings. 

PMID- 24458909
TI  - Plasmonic nanobiosensor with chain reaction amplification mechanism.
AB  - Herein we demonstrate a plasmonic nanobiosensor that explores chain reaction
      amplification mechanisms to transduce chemical signals released in biocatalytic
      reactions, turning optical signals into a visual spectral range. The sensor has a
      very simple design: gold nanoparticles resting in the surface of a grafted P2VP
      film. Changes in the gold nanoparticles' position causes changes in the plasmon
      coupling mode. This is detected by means of a maximum absorbance shift. 

PMID- 24458910
TI  - Total synthesis of chiriquitoxin, an analogue of tetrodotoxin isolated from the
      skin of a dart frog.
AB  - The first total synthesis of chiriquitoxin, the most structurally complex
      analogue of tetrodotoxin isolated from a Costa Rican dart frog, has been
      accomplished from a newly designed intermediate for a variety of tetrodotoxin
      derivatives. The synthesis includes the third total synthesis of tetrodotoxin in
      this laboratory, and its intermediate was transformed into chiriquitoxin by a
      stereocontrolled aldol reaction with a D-camphor-derived lactone for installation
      of the unique side chain, and a new deprotection of methylthiomethyl (MTM) ether
      by using a Pummerer rearrangement.

PMID- 24458911
TI  - From homoconjugated push-pull chromophores to donor-acceptor-substituted spiro
      systems by thermal rearrangement.
AB  - Series of homoconjugated push-pull chromophores and donor-acceptor (D-A)
      functionalized spiro compounds were synthesized, in which the electron-donating
      strength of the anilino donor groups was systematically varied. The structural
      and optoelectronic properties of the compounds were investigated by X-ray
      analysis, UV/Vis spectroscopy, electrochemistry, and computational analysis. The
      homoconjugated push-pull chromophores with a central bicyclo[4.2.0]octane
      scaffold were obtained in high yield by [2+2] cycloaddition of 2,3-dichloro-5,6
      dicyano-p-benzoquinone (DDQ) to N,N-dialkylanilino- or N,N-diarylanilino
      substituted activated alkynes. The spirocyclic compounds were formed by thermal
      rearrangement of the homoconjugated adducts. They also can be prepared in a one
      pot reaction starting from DDQ and anilino-substituted alkynes. Spiro products
      with N,N-diphenylanilino and N,N-diisopropylanilino groups were isolated in high
      yields whereas compounds with pyrrolidino, didodecylamino, and dimethylamino
      substituents gave poor yields, with formation of insoluble side products. It was
      shown by in situ trapping experiments with TCNE that cycloreversion is possible
      during the thermal rearrangement, thereby liberating DDQ. In the low-yielding
      transformations, DDQ oxidizes the anilino species present, presumably via an
      intermediate iminium ion pathway. Such a pathway is not available for the N,N
      diphenylanilino derivative and, in the case of the N,N-diisopropylanilino
      derivative, would generate a strained iminium ion (A1,3 strain). The mechanism of
      the thermal rearrangement was investigated by EPR spectroscopy, which provides
      good evidence for a proposed biradical pathway starting with the homolytic
      cleavage of the most strained (CN)C-C(CN) bond between the fused four- and six
      membered rings in the homoconjugated adducts.

PMID- 24458912
TI  - Surface chemistry on small ruthenium nanoparticles: evidence for site selective
      reactions and influence of ligands.
AB  - The reactivity of two classes of ruthenium nanoparticles (Ru NPs) of small size,
      either sterically stabilized by a polymer (polyvinylpyrrolidone, PVP) or
      electronically stabilized by a ligand (bisdiphenylphosphinobutane, dppb) was
      tested towards standard reactions, namely CO oxidation, CO2 reduction and styrene
      hydrogenation. The aim of the work was to identify the sites of reactivity on the
      nanoparticles and to study how the presence of ancillary ligands can influence
      the course of these catalytic reactions by using NMR and IR spectroscopies. It
      was found that CO oxidation proceeds at room temperature (RT) on Ru NPs but that
      the system deactivates rapidly in the absence of ligands because of the formation
      of RuO2. In the presence of ligands, the reaction involves exclusively the
      bridging CO groups and no bulk oxidation is observed at RT under catalytic
      conditions. The reverse reaction, CO2 reduction, is achieved at 120  degrees C in
      the presence of H2 and leads to CO, which coordinates exclusively in a bridging
      mode, hence evidencing the competition between hydrides and CO for coordination
      on Ru NPs. The effect of ligands localized on the surface is also evidenced in
      catalytic reactions. Thus, styrene is slowly hydrogenated at RT by the two
      systems Ru/PVP and Ru/dppb, first into ethylbenzene and then into
      ethylcyclohexane. Selectively poisoning the nanoparticles with bridging CO groups
      leads to catalysts that are only able to reduce the vinyl group of styrene
      whereas a full poisoning with both terminal and bridging CO groups leads to
      inactive catalysts. These results are interpreted in terms of location of the
      ligands on the particles surface, and evidence site selectivity for both CO
      oxidation and arene hydrogenation.

PMID- 24458914
TI  - Effect of functionalized groups on gas-adsorption properties: syntheses of
      functionalized microporous metal-organic frameworks and their high gas-storage
      capacity.
AB  - The microporous metal-organic framework (MMOF) Zn4O(L1)2?9 DMF?9 H2O (1-H) and
      its functionalized derivatives Zn4O(L1-CH3)2?9 DMF?9 H2O (2-CH3) and Zn4O(L1
      Cl)2?9 DMF?9 H2O (3-Cl) have been synthesized and characterized (H3L1=4-[N,N
      bis(4-methylbenzoic acid)amino]benzoic acid, H3L1-CH3=4-[N,N-bis(4-methylbenzoic
      acid)amino]-2-methylbenzoic acid, H3L1-Cl=4-[N,N-bis(4-methylbenzoic acid)amino]
      2-chlorobenzoic acid). Single-crystal X-ray diffraction analyses confirmed that
      the two functionalized MMOFs are isostructural to their parent MMOF, and are
      twofold interpenetrated three-dimensional (3D) microporous frameworks. All of the
      samples possess enduring porosity with Langmuir surface areas over 1950 cm(2) g(
      1). Their pore volumes and surface areas decrease in the order 1-H>2-CH3 >3-Cl.
      Gas-adsorption studies show that the H2 uptakes of these samples are among the
      highest of the MMOFs (2.37 wt% for 3-Cl at 77 K and 1 bar), although their
      structures are interpenetrating. Furthermore, this work reveals that the
      adsorbate-adsorbent interaction plays a more important role in the gas-adsorption
      properties of these samples at low pressure, whereas the effects of the pore
      volumes and surface areas dominate the gas-adsorption properties at high
      pressure.

PMID- 24458913
TI  - Efficient copper-catalyzed direct intramolecular aminotrifluoromethylation of
      unactivated alkenes with diverse nitrogen-based nucleophiles.
AB  - A mild, convenient, and step-economical intramolecular aminotrifluoromethylation
      of unactivated alkenes with a variety of electronically distinct, nitrogen-based
      nucleophiles in the presence of a simple copper salt catalyst, in the absence of
      extra ligands, is described. Many different nitrogen-based nucleophiles (e.g.,
      basic primary aliphatic and aromatic amines, sulfonamides, carbamates, and ureas)
      can be employed in this new aminotrifluoromethylation reaction. The
      aminotrifluoromethylation process allows straightforward access to diversely
      substituted CF3-containing pyrrolidines or indolines, in good to excellent
      yields, through a direct difunctionalization strategy from the respective acyclic
      starting materials. Mechanistic studies were conducted and a plausible mechanism
      was proposed.

PMID- 24458915
TI  - Boryl-functionalized sigma-alkynyl and vinylidene rhodium complexes: synthesis
      and electronic properties.
AB  - The synthesis, reactivity, and properties of boryl-functionalized sigma-alkynyl
      and vinylidene rhodium complexes such as trans-[RhCl(=C=CHBMes2)(PiPr3)2] and
      trans-[Rh(C=CBMes2)(IMe)(PiPr3)2] are reported. An equilibrium was found to exist
      between rhodium vinylidene complexes and the corresponding hydrido sigma-alkynyl
      complexes in solution. The complex trans-[Rh(C=CBMes2)(IMe)(PiPr3)2] (IMe=1,3
      dimethylimidazol-2-ylidene) was found to exhibit solvatochromism and can be
      quasireversibly oxidized and reduced electrochemically. Density functional
      calculations were performed to determine the reaction mechanism and to help
      rationalize the photophysical properties of trans-[Rh(C=CBMes2)(IMe)(PiPr3)2].

PMID- 24458916
TI  - Electrophile-induced nucleophilic substitution of the nido-dicarbaundecaborate
      anion nido-7,8-C2B9H12- by conjugated heterodienes.
AB  - Substitution of the dicarbaundecaborate anion nido-7,8-C2B9H12(-) (1) by precise
      hydride abstraction followed by nucleophilic attack usually leads to symmetric
      products 10-R-nido-7,8-C2B9H11. However, thioacetamide (MeC(S)NH2) as nucleophile
      and acetone/AlCl3 as hydride abstractor gave asymmetric 9-[MeC(NHiPr)S]-nido-7,8
      C2B9H11 (2), whereas N,N-dimethylthioacetamide (MeC(S)NMe2) gave the expected
      symmetric 10-[MeC(NMe2)S]-nido-7,8-C2B9H11 (4). For the formation of 2, acetone
      and thioacetamide are assumed to give the intermediate MeC(S)N(CMe2) (3), which
      then attacks 1 with formation of 2. Similarly, reaction of acetyliminium chloride
      [MeC(O)NH(CPh2)]Cl (5) with 1 in THF gave a mixture of 9- and 10-substituted
      [MeC(NHCHPh2)O]-nido-7,8-C2B9H11 (6 and 7, respectively). These reactions are the
      first examples in which compounds (here heterodienes) that unite the
      functionalities of both hydride acceptor and nucleophilic site react with 1 in a
      bimolecular fashion. Furthermore, the analogous reaction of 1 and 5 (in an
      equilibrium mixture with acetyl chloride and benzophenone imine) in MeCN afforded
      10-[MeC(NCPh2)NH]-nido-7,8-C2B9H11 (8) and MeC(O)NHCHPh2 (9).

PMID- 24458917
TI  - A stable microporous mixed-metal metal-organic framework with highly active Cu2+
      sites for efficient cross-dehydrogenative coupling reactions.
AB  - Two metalloporphyrin octacarboxylates were used to link copper(II) nodes for the
      formation of two novel porous mixed-metal metal-organic frameworks (M'MOFs)
      containing nanopore cages (2.1 nm in diameter) or nanotubular channels (1.5 nm in
      diameter). The highly active Cu(2+) sites on the nanotubular surfaces of the
      stable porous M'MOF ZJU-22, stabilized by three-connected nets, lead to the
      superior catalytic activity for the cross-dehydrogenative coupling (CDC)
      reaction. 

PMID- 24458918
TI  - Equine pulmonary aspergillosis with encephalitic, myocardial, and renal
      dissemination.
AB  - The cause of the death of a 16-month-old Brasileiro-de-Hipismo filly and a 3-year
      old male Paint Horse with clinical manifestations of anemia and apathy from
      southern Brazil was investigated. These horses were maintained at the same
      stable; received hay as part of their diet and were submitted for routine
      necropsy evaluations. Significant gross findings included several nodules
      randomly distributed throughout the pulmonary lobes of both horses, and the
      kidneys, myocardium, and the frontal lobes of the cerebrum of the filly.
      Histopathological evaluation revealed pyogranulomatous bronchopneumonia in both
      horses; granulomatous interstitial nephritis, myocarditis, and encephalitis were
      observed in the filly. All lesions contained vasculitis and thrombosis associated
      with myriads of intralesional, branching, septate fungi consistent with
      Aspergillus spp.; intralesional fungi were more easily identified by the Grocott
      methenamine silver stain. Mycological culture of fresh pulmonary sections from
      both horses and the brain of the filly revealed pure growths of A. fumigatus.
      These findings confirmed the participation of A. fumigatus in the
      etiopathogenesis of the lesions observed in the lungs of both horses, and the
      cerebrum, myocardium and kidneys of the filly and might represent the first
      description of A. fumigatus-induced encephalitis in horses. Additionally, we
      believe that infection occurred during the ingestion of contaminated hay or by
      inhalation of spores within contaminated bedding that resulted in transient nasal
      mycosis, which progressed to pyogranulomatous bronchopneumonia in both horses
      with embolic encephalitic, myocardial, and renal dissemination of A. fumigatus
      occurring only in the filly.

PMID- 24458919
TI  - Characterization of a galactosynthase derived from Bacillus circulans beta
      galactosidase: facile synthesis of D-lacto- and D-galacto-N-bioside.
AB  - Glycosynthases-retaining glycosidases mutated at their catalytic nucleophile
      catalyze the formation of glycosidic bonds from glycosyl fluorides as donor
      sugars and various glycosides as acceptor sugars. Here the first glycosynthase
      derived from a family 35 beta-galactosidase is described. The Glu->Gly mutant of
      BgaC from Bacillus circulans (BgaC-E233G) catalyzed regioselective
      galactosylation at the 3-position of the sugar acceptors with alpha-galactosyl
      fluoride as the donor. Transfer to 4-nitophenyl alpha-D-N-acetyl-glucosaminide
      and alpha-D-N-acetylgalactosaminide yielded 4-nitophenyl alpha-lacto-N-biose and
      alpha-galacto-N-biose, respectively, in high yields (up to 98%). Kinetic analysis
      revealed that the high affinity of the acceptors contributed mostly to the BgaC
      E233G-catalyzed transglycosylation. BgaC-E233G showed no activity with beta-(1,3)
      linked disaccharides as acceptors, thus suggesting that this enzyme can be used
      in "one-pot synthesis" of LNB- or GNB-containing glycans.

PMID- 24458920
TI  - In vitro and in vivo experiments with iron oxide nanoparticles functionalized
      with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting.
AB  - In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide
      superparamagnetic nanoparticles were synthetized and their cytotoxicity and
      biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed
      by a thermal decomposition process with d = 18 nm and sigma = 2 nm; finally, the
      character of SPIONs was changed to hydrophilic by a post-synthesis procedure with
      the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles
      present high saturation magnetization and superparamagnetic behavior at room
      temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs
      were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs
      have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac
      magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro
      studies using VERO and MDCK cell lineages were performed to study the
      cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and
      DEXTRAN-coated nanoparticles presented high cell viability for concentrations as
      high as 200 MUg/mL. In vivo studies were conducted using BALB/c mice inoculating
      the SPIONs intravenously and exposing them to the presence of an external magnet
      located over the tumour. It was observed that the amount of PEG-coated SPIONs in
      the tumor increased by up to 160% when using the external permanent magnetic as
      opposed to those animals that were not exposed to the external magnetic field.

PMID- 24458921
TI  - The essential oil of bergamot stimulates reactive oxygen species production in
      human polymorphonuclear leukocytes.
AB  - Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in
      folk medicine as an antiseptic and anthelminthic and to facilitate wound healing.
      Evidence indicates that BEO has substantial antimicrobial activity; however its
      effects on immunity have never been examined. We studied the effects of BEO on
      reactive oxygen species (ROS) production in human polymorphonuclear leukocytes
      (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these
      cells. Results show that BEO increased intracellular ROS production in human PMN,
      an effect that required the contribution of extracellular (and, to a lesser
      extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly
      increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe
      and reduced the response to the protein kinase C activator phorbol myristate
      acetate. In conclusion, this is the first report showing the ability of BEO to
      increase ROS production in human PMN. This effect could both contribute to the
      activity of BEO in infections and in tissue healing as well as underlie an
      intrinsic proinflammatory potential. The relevance of these findings for the
      clinical uses of BEO needs careful consideration.

PMID- 24458922
TI  - CALR mutations in myeloproliferative neoplasms: hidden behind the reticulum.

PMID- 24458923
TI  - Electrical properties of the salt gland of Aegiceras.
AB  - Microelectrode and current clamping techniques have been used to investigate the
      electrical properties of the salt gland of Aegiceras corniculatum Blanco. Three
      regions of the gland corresponding to the cuticular cap, secretory cells, and the
      basal cell are distinguishable according to their resting potential and voltage
      response characteristics. The resting potentials of the secretory cells and basal
      cells are shown to be markedly negative with respect to the cuticular cap and the
      surface of the gland. Penetration of the base of the gland always results in a
      sharp drop in the resting potential. It is also shown that there exists a low
      resistance pathway from the cuticular region to the underside of the gland which
      shunts the secretory cells, and that the cuticular cap presents a high electrical
      resistance. The resting potential and voltage response at various positions in
      the gland were also measured with variation in leaf illumination. It is shown
      that the resting potential becomes less negative throughout the gland for the
      transition light to dark. A similar change in illumination generally produces a
      rise in voltage response. 

PMID- 24458924
TI  - [Cell wall breakdown in wilting flowers of Ipomoea tricolor Cav].
AB  - In Ipomoea tricolor senescence of the corolla is characterized by a decrease of
      hemicellulose and cellulose contents by 43% and 40%, respectively. Concomitant
      with the mobilization of cell wall polysaccharides the activities of various
      glycosidases, beta-glucosidase, beta-galactosidase, laminarinase, and cellobiase
      increase considerably. In contrast, the increase of alpha-mannosidase activity is
      less marked and the activity of beta-xylosidase reaches its maximum in the course
      of extension growth of the flower bud. The partial degradation of the cell walls
      followed by the withdrawal of sugars as well as the mobilization of intracellular
      compounds may be meaningful with regard to the capacity of Ipomoea to form an
      enormous number of flowers consecutively. 

PMID- 24458925
TI  - Effects of light, temperature, pH, and inhibitors on the ATP level of the blue
      green alga Anacystic nidulans.
AB  - The dependence of the ATP level of the blue-green alga Anacystis nidulans on
      light intensity (300-20000 erg.cm(-2).s(-1) white light) and on temperature (0-50
      degrees ), pH (6.5-9.0), and phosphate concentration (up to 10(-1) M) in light
      (20000 lx) and dark was measured. In contrast to a low ATP level in darkness the
      level in light remains high and constant with each treatment in a broad range of
      the respective scales. DCMU [3-(3',4'-dichlorophenyl)-l,1-dimethyl-urea)] (5*10(
      6) M) has no effect on the ATP pool in light, supporting the view that the ATP
      level is maintained by cyclic photophosphorylation. Dio-9, an inhibitor of energy
      transfer, lowers the ATP level according to concentration in light and dark. The
      unchanged ATP level after transitions from N2 to N2+CO2 under different
      conditions indicates an intensive regulation of the ATP pool. The ADP level,
      where measured, was found to be inverse to the ATP level. These results are
      discussed in comparison with data collected by other authors using different
      organisms. 

PMID- 24458926
TI  - Morphogenetic role of kinetin and abscisic acid in the moss Physcomitrium.
AB  - In the presence of kinetin, a supposedly gametophytic bud inducing substance, the
      secondary protonema of the moss Physcomitrium pyriforme Brid., as well as
      producing leafy gametophytes, continued to exhibit its normal tendency of forming
      sporophytic buds (i.e. buds with apical cells having two cutting faces). Also
      remarkable was that callus derived from the secondary protonema, when cultured in
      a kinetin supplemented liquid medium, formed exclusively apogamous sporophytic
      buds with a virtual exclusion of gametophytes. In the presence of abscisic acid,
      the elongation of protonemal cells as well as their differentiation was markedly
      suppressed. This effect was manifest even when abscisic acid was used in
      conjunction with kinetin. It is suggested that rather than having a
      morphoregulatory role, kinetin may be responsible merely for enhancing cell
      proliferation. The determination of an apical cell with two cutting faces
      (sporophytic) or one with three cutting faces (gametophytic) is under the control
      of other factors both external, (e.g. sucrose) and internal. It is proposed that
      abscisic acid can suppress the usual differentiational capacity of the moss
      tissue, even in a favourable environment. 

PMID- 24458927
TI  - The isoenzyme distribution of etiolated pea seedling lipoxygenase.
AB  - Acetone powders from etiolated dwarf pea seedlings (Pisum sativum.) contain
      lipoxygenase activity that can be separated by carboxymethylcellulose
      chromatography into 5 active fractions. The total lipoxygenase activity and the
      distribution of activity among the fractions changes with seedling age. Both stem
      and leaf tissue contain lipoxygenase activity. Two active fractions are specific
      to leaf tissue, one to stem tissue, while the other two fractions are common to
      both. These isoenzyme distributions are compared with that in pea seeds. 

PMID- 24458928
TI  - Regulators of cell division in plant tissues : XVIII. Metabolism of zeatin in Zea
      mays seedlings.
AB  - [(3)H] Zeatin was supplied to Zea mays L. seedlings with roots excised; the
      metabolites identified were adenosine-5'-phosphate, adenosine, adenine, and 7
      glucosylzeatin (a minor metabolite). The principal metabolites formed from zeatin
      by the roots of intact Z. mays seedlings were adenosine-5'-phosphate, zeatin
      riboside-5'-phosphate, zeatin riboside, adenine, adenosine and an unknown
      compound termed Y. This was isolated and identified as 9-glucosylzeatin. This
      glucoside also appeared to form from zeatin in cultured embryonic tissue of Z.
      mays. 

PMID- 24458929
TI  - Stimulation of Avena coleoptile growth by reduction of oxygen supply.
AB  - The growth of Avena sativa L. coleoptiles was accelerated by reduction of the O2
      concentration in the surrounding atmosphere. Cell-wall extensibility was
      increased in close relation to the increase in elongation, 6-8% O2 giving the
      optimal effect in either case. Growth promotion by reduced O2 concentration and
      by auxin (indole-3-acetic acid; IAA) were additive, at least at lower auxin
      concentrations.This response to reduced O2 concentration was also present in
      sections pretreated with cycloheximide for 2 h, although such sections showed no
      response to applied IAA. No significant change was observed in auxin transport
      under reduced O2 supply. It is suggested that the acceleration of cell elongation
      and the loosening of cell wall by reduced O2 supply are due to a mechanism which
      is not directly dependent on auxin-induced growth. We propose to designate this
      acceleration of growth under reduced O2 concentrations as oxygen-sensitive
      growth. 

PMID- 24458930
TI  - A method for high-frequency intergeneric fusion of plant protoplasts.
AB  - Protoplasts of Vicia hajastana Grossh. obtained from suspension-culture cells and
      Pisum sativum L. obtained from leaves adhered tightly to each other in
      concentrated solutions of high-molecular-weight polyethylene glycol (PEG). The
      adhesion occurred non-specifically between the free protoplasts from the same
      species as well as from the different species and genus. It was enhanced by
      enrichment of the PEG solution with calcium. Very few heteroplasmic fusions
      occurred during the period when the protoplasts were incubated in the PEG
      solution. However, many heterokaryons (up to 10%) were formed soon after the PEG
      solution was diluted out. The same phenomena were also observed in protoplasts
      from suspension-culture cells of Glycine max L. and from leaves of Hordeum
      vulgare L. Vicia and soybean protoplasts obtained from cultured cells regenerated
      cell walls and underwent sustained cell division after such treatment. Some Vicia
      pea heterokaryons divided once. Over 10% of the soybean-barley hybrids divided in
      7 days. Some divided 4-5 times and formed small clusters of cells in 10 days. The
      hybrids were recognizable because they contained chloroplasts from the leaf
      protoplast and exhibited morphological characters typical of the chlorophyll-less
      cells. None of the protoplasts from pea and barley leaves, either with or without
      PEG treatment, underwent cell division during the period of observation. The
      mechanism of adhesion and fusion of the protoplasts has been discussed. 

PMID- 24458931
TI  - Temperature dependence of the permeability of chloroplasts from chilling
      sensitive and chilling-resistant plants.
AB  - Osmotic responses of chloroplasts from chilling-resistant (Pisum sativum L.,
      Spinacia oleracea L.) and chilling-sensitive (Phaseolus vulgaris L., Lycopersicon
      esculentum Mill.) plants to glycerol and erythritol were determined from 1
      degrees  to 28 degrees . The permeability of the chloroplast limiting membranes,
      as measured by reflection coefficients, decreased when the temperature was
      raised. For Pisum and Spinacia the curves relating reflection coefficients and
      temperature were smooth, while for Phaseolus and Lycopersicon breaks occurred
      near 11 degrees . The break may indicate a phase transition in the membranes, the
      change leading to a higher chloroplast permeability at lower temperatures for
      chilling-sensitive plants. 

PMID- 24458932
TI  - Hypochlorite and tissue sterilization.
AB  - Trace amounts of sodium hypochlorite that remain on the surface of seeds
      (Lycopersicon esculentum Mill.) after sterilization interfere with subsequent
      uptake and incorporation of leucine into protein when the seeds are used in
      metabolic studies. The hypochlorite can be washed away with 0.01 N HCl but not by
      washing several times with water. 

PMID- 24458933
TI  - Letter regarding article by Xu et al.: anterior versus posterior approach for
      treatment of thoracolumbar burst fractures: a meta-analysis.

PMID- 24458934
TI  - Should age be a contraindication for degenerative lumbar surgery?
AB  - INTRODUCTION AND PURPOSE: The purpose of this study was to evaluate and compare
      disability, quality of life and satisfaction outcomes between young people and
      elderly who were operated on for degenerative lumbar disease. MATERIAL AND
      METHODS: A database of 263 patients undergoing lumbar surgery for degenerative
      conditions was collected. There were 74 patients who were 65 years old or above
      and 189 who were below 65 who had complete preoperative and 2-year postoperative
      HRQOL data measures: ODI, SF-36 and COMI. RESULTS: There were no significant
      differences in the outcomes between the two age groups (p > 0.05). An improvement
      from baseline in all quality of life measures in the two age groups was observed.
      A median improvement of 6.0 points was found in the ODI in the younger patients
      versus 12.0 in older ones. A median improvement in the SF36 physical component
      score of 6.95 was seen in the younger group while improvement was reported at
      6.36 points in patients over 65. The SF36 mental component score improved by 4.48
      points and 4.96 points, respectively. COMI improved a median of 1.2 points in
      both groups. In terms of satisfaction, 66.9 % of the younger patients were
      pleased or very pleased whereas this was found to be 59.7 % for the older group.
      CONCLUSION: Older patients can see substantial clinical improvement after
      degenerative lumbar disease surgery similar to that obtained in younger patients
      in terms of quality of life and satisfaction. The improvement in terms of the
      disability is greater for older patients. Thus, age should not be a
      contraindication for this procedure.

PMID- 24458935
TI  - The role of needle tip position on the accuracy of diagnostic selective nerve
      root blocks in spinal deformity.
AB  - PURPOSE: The specificity of a selective nerve root block (SNRB) is dependant on
      isolating only the required nerve root whilst avoiding injectate flow to
      traversing nerves. Needle tip position is therefore crucial. Nerve root blocks
      (SNRBs) in the presence of deformity can be particularly technically challenging
      to perform. The aims of this study were to document the relationship of needle
      tip position and SNRB accuracy in patients with and without spinal deformity.
      METHODS: Over an 8-month period, all SNRBs performed by one spinal surgeon were
      included. Patients with radiographic evidence of spinal deformity were analysed
      separately and their lumbar deformity graded using the Schwab grading system.
      Needle tip position in relation to the superior pedicle and flow of contrast was
      documented. RESULTS: 76 patients received 85 injections without deformity, 26
      patients with deformity underwent 30 SNRBs. In the normal spinal alignment group,
      there was on overall accuracy of 70.1% regardless of needle tip position, which
      improved to 91.8% for a lateral needle tip position (P < 0.001). In patients with
      deformity, the overall accuracy was significantly lower irrespective of needle
      tip position 36 versus 70%, respectively (P < 0.0019). CONCLUSIONS: Selective
      nerve root blocks are accurate in patients without deformity where a needle tip
      placement lateral to the middle third of the pedicle is achieved. The presence of
      spinal deformity significantly reduces the accuracy of SNRBs with a higher chance
      of epidural infiltration.

PMID- 24458936
TI  - The influence of comorbidity on the risks and benefits of spine surgery for
      degenerative lumbar disorders.
AB  - PURPOSE: The ageing of the population will see a growing number of patients
      presenting for spine surgery with appropriate indications but numerous medical
      comorbidities. This complicates decision-making, requiring that the likely
      benefit of surgery (outcome) be carefully weighed up against the potential risk
      (complications). We assessed the influence of comorbidity on the risks and
      benefits of spine surgery. METHODS: 3,549/4,053 patients with degenerative lumbar
      disorders, undergoing surgery with the goal of pain relief, completed the
      multidimensional Core Outcome Measures Index (COMI; scored 0-10) before and 12
      months after surgery. At 12 months postoperatively, they also rated the global
      treatment outcome and their satisfaction with care. Using the Eurospine Spine
      Tango Registry, surgeons documented surgical details, American Society of
      Anesthesiologists comorbidity (ASA) grades and perioperative surgical and general
      complications. RESULTS: 29.0% patients were rated as ASA1 (normal healthy), 45.7%
      as ASA2 (mild/moderate systemic disease), 24.9% as ASA3 (severe), and just 0.4%
      as ASA4 (life-threatening). In going from ASA1 to ASA3 (ASA4 group too small),
      surgical complications increased significantly from 5.0 to 14.5% and general
      complications increased from 2.9 to 15.7%; 12-month outcomes showed a
      corresponding decline, with a good global outcome being reported by 79% ASA1
      patients, 76% ASA2, and 68% ASA3. Satisfaction with treatment was 87, 85, and
      79%, respectively, and reduction in COMI was 4.2 +/- 2.9, 3.7 +/- 3.0, and 3.4 +/
      3.0 points, respectively. Multiple regression analysis revealed a significant (p
      < 0.0001) independent effect of ASA grade on both complications and outcome.
      CONCLUSION: The negative impact of comorbidity on the outcome of spine surgery
      has not been well investigated/quantified to date. The ASA grade may be helpful
      in producing algorithms for decision-making and preoperative counselling
      regarding the corresponding risks and benefits of surgery.

PMID- 24458937
TI  - Complications in spinal deformity surgery in the United Kingdom: 5-year results
      of the annual British Scoliosis Society National Audit of Morbidity and
      Mortality.
AB  - PURPOSE: To provide a 5-year national overview of corrective spinal deformity
      surgery in the United Kingdom. METHODS: Since 2008, the British Scoliosis Society
      has collected predefined data on spinal deformity surgeries carried out by its
      members. Participating units collect and submit annual anonymised data pertaining
      to the number of deformity surgeries performed, age groups, aetiology (idiopathic
      versus non-idiopathic), mortality, deep infections and neurological deficit
      (complete, incomplete without resolution and incomplete with resolution). Overall
      aetiology proportions and complication rates were calculated, as well as funnel
      plots with control limits of individual complication rates by cases performed.
      RESULTS: Between 2008 and 2012, 9,295 corrective spinal deformity procedures were
      performed. 4,445 (48%) were recorded as idiopathic and 2,917 (31%) as non
      idiopathic. There were a total of 339 complications (3.6%). Deep infections
      occurred in 222 (2.82%), incomplete neurological deficit with resolution in 59
      (0.65%), incomplete neurological deficit without resolution in 29 (0.32%),
      complete neurological deficit in 12 (0.13%) and mortality in 17 (0.19%).
      CONCLUSION: The complication rates reported in this study compare well with
      previously published studies. These reported results will hopefully serve to
      provide a benchmark for units in the UK providing corrective spinal deformity
      surgery to allow individual units to compare their complication rates against
      national averages and to provide national complication figures to aid in the
      consenting process of patients. Use of a spinal deformity registry, such as the
      British Spine Registry, is required to ensure ongoing service development and
      optimal healthcare provision.

PMID- 24458939
TI  - Bioaccumulation and biotransformation of arsenic compounds in Hediste
      diversicolor (Muller 1776) after exposure to spiked sediments.
AB  - This study focused on the exposure of the common ragworm Hediste diversicolor
      (Muller 1776) to sediments enriched with different arsenic compounds, namely
      arsenate, dimethyl-arsinate, and arsenobetaine. Speciation analysis was carried
      out on both the spiked sediments and the exposed polychaetes in order to
      investigate H. diversicolor capability of arsenic bioaccumulation and
      biotransformation. Two levels of contamination (acute and moderate dose) were
      chosen for enriched sediments to investigate possible differences in the arsenic
      bioaccumulation patterns. The highest value of arsenic in tissues was reached
      after 15 days of exposure to dimethyl-arsinate (acute dose) spiked sediment
      (1,172 +/- 176 MUg/g). A significant increase was also obtained in worms exposed
      both to arsenate and arsenobetaine. Speciation analysis showed that trimethyl
      arsine oxide was the predominant chemical form in tissues of H. diversicolor
      exposed to all the spiked sediments, confirming the importance of this
      intermediate in biological transformation of arsenic. 

PMID- 24458938
TI  - Nano-silver in drinking water and drinking water sources: stability and
      influences on disinfection by-product formation.
AB  - Nano-silver is increasingly used in consumer products from washing machines and
      refrigerators to devices marketed for the disinfection of drinking water or
      recreational water. The nano-silver in these products may be released, ending up
      in surface water bodies which may be used as drinking water sources. Little
      information is available about the stability of the nano-silver in sources of
      drinking water, its fate during drinking water disinfection processes, and its
      interaction with disinfection agents and disinfection by-products (DBPs). This
      study aims to investigate the stability of nano-silver in drinking water sources
      and in the finished drinking water when chlorine and chloramines are used for
      disinfection and to observe changes in the composition of DBPs formed when nano
      silver is present in the source water. A dispersion of nano-silver particles (10
      nm; PVP-coated) was used to spike untreated Ottawa River water, treated Ottawa
      River water, organic-free water, and a groundwater at concentrations of 5 mg/L.
      The diluted dispersions were kept under stirred and non-stirred conditions for up
      to 9 months and analyzed weekly using UV absorption to assess the stability of
      the nano-silver particles. In a separate experiment, Ottawa River water
      containing nano-silver particles (at 0.1 and 1 mg/L concentration, respectively)
      was disinfected by adding sodium hypochlorite (a chlorinating agent) in
      sufficient amounts to maintain a free chlorine residual of approximately 0.4 mg/L
      after 24 h. The disinfected drinking water was then quenched with ascorbic acid
      and analyzed for 34 neutral DBPs (trihalomethanes, haloacetonitriles,
      haloacetaldehydes, 1,1 dichloro-2-propanone, 1,1,1 trichloro-2-propanone,
      chloropicrin, and cyanogen chloride). The results were compared to the profile of
      DBPs obtained under the same conditions in the absence of nano-silver and in the
      presence of an equivalent concentration of Ag(+) ions (as AgNO3). The stability
      of the nano-silver dispersions in untreated Ottawa River water, with a dissolved
      organic carbon concentration of 6 mg/L, was significantly higher than the
      stability of the nano-silver dispersions in distilled, organic-free water. Nano
      silver particles suspended in the groundwater agglomerated and were quickly and
      quantitatively removed from the solution. Our data confirm previous observations
      that natural dissolved organic matter stabilizes nano-silver particles, while the
      high-ionic strength of groundwater appears to favor their agglomeration and
      precipitation. As expected, nano-silver was not stable in Ottawa River water
      through the chlorination process, but survived for many days when added to the
      Ottawa River water after treatment with chlorine or chloramines. Stirring
      appeared to have minimal effect on nano-silver stability in untreated and treated
      Ottawa River water. The profile of DBPs formed in the presence of nAg differed
      significantly from the profile of DBPs formed in the absence of nAg only at the 1
      mg/L nAg concentration. The differences observed consisted mainly in reduced
      formation of some brominated DBPs and a small increase in the formation of
      cyanogen chloride. The reduced formation of brominated congeners may be explained
      by the decrease in available bromide due to the presence of Ag(+) ions. It should
      be noted that a concentration of 1 mg/L is significantly higher than nAg
      concentrations that would be expected to be present in surface waters, but these
      results could be significant for the disinfection of some wastewaters with
      comparably high nano-silver concentrations.

PMID- 24458940
TI  - Impacts on effluent contaminants from mine sites: risk assessment, fate, and
      distribution of pollution at basin scale.
AB  - The environmental implications of mining activities are of worldwide concern. An
      environmental evaluation at the basin level was conducted because of widespread
      mining in Cajamarca in Northern Peru. A sediment monitoring program was developed
      at the Jequetepeque basin, located in Cajamarca. A total of 16 sites were
      monitored at three different times between June 2009 and July 2010, and a total
      of 42 samples were collected. All samples were analyzed by microwave digestion
      and by a sequential extraction scheme following the three-stage European
      Community Bureau of Reference (three-stage BCR) protocol. Trace element
      mobilization from the sediments to the water column was assessed by the risk
      assessment code (RAC). Spatial and temporal distribution of trace elements was
      evaluated by principal component analysis and hierarchical cluster analysis. Cd,
      Zn, As, and Pb showed the highest concentrations independent of season. Notably,
      Cu concentration and mobility increased during the wet season for all samples.
      Additionally, Hg concentration and mobility increased during the wet season near
      the mine sites. According to the enrichment factor, the highest enrichments of
      Cd, Zn, Pb, and As were related to mine runoff. The effect of trace elements near
      the mine sites at the Jequetepeque basin was considered a significant threat to
      the environment due to Cd, Zn, Pb, and As, and the concentrations of Cu and Hg
      were also considered a concern. This work establishes a baseline for the
      environmental quality status of the Jequetepeque basin that may support water
      quality management in Peru. 

PMID- 24458941
TI  - Somatotopic changes in the nucleus ambiguus after section and regeneration of the
      recurrent laryngeal nerve of the rat.
AB  - Changes in motoneurons innervating laryngeal muscles after section and
      regeneration of the recurrent laryngeal nerve (RLN) are far from being
      understood. Here, we report the somatotopic changes within the nucleus ambiguus
      (Amb) after the nerve injury and relates it to the resulting laryngeal fold
      impairment. The left RLN of each animal was transected and the stumps were glued
      together using surgical fibrin glue. After several survival periods (1, 2, 4, 8,
      12, 16 weeks; at least six rats at each time point) the posterior cricoarytenoid
      (PCA) and thyroarytenoid (TA) muscles were injected with fluorescent-conjugated
      cholera toxin and the motility of the vocal folds evaluated. After section and
      subsequent repair of the RLN, no movement of the vocal folds could be detected at
      any of the survival times studied and the somatotopy and the number of labeled
      motoneurons changed. From 4 wpi award, the somatotopy was significantly
      disorganized, with the PCA motoneurons being located rostrally relative to their
      normal location. A rostrocaudal overlap between the two pools of motoneurons
      supplying the PCA and TA muscles was observed from 2 wpi onwards. Hardly any
      labeled neurons were found in the contralateral Amb in any of the experimental
      groups. An injury of the RLN leads to a reinnervation of the denervated motor
      endplates of PCA and TA. However, misdirected axons sprout and regrowth from the
      proximal stump to the larynx. As a result, misplaced innervation of muscles
      results in a lack of functional recovery of the laryngeal folds movement
      following a RLN injury.

PMID- 24458942
TI  - Latissimus dorsi tendon transfer for irreparable postero-superior cuff tears:
      current concepts, indications, and recent advances.
AB  - Latissimus dorsi tendon transfer is a method for surgical treatment of massive
      irreparable posterosuperior cuff tears. It partially restores active anteflexion,
      external rotation, and function of the shoulder but does not significantly
      increase strength of the shoulder. It is contraindicated in case of
      pseudoparalytic shoulder; associated irreparable subscapularis tear, deltoid
      palsy, and in case of associated osteoarthritis, as an isolated procedure.
      Results are inferior when performed as a secondary procedure compared with a
      primary procedure. However, latissimus dorsi tendon transfer is an attractive
      solution to improve shoulder mobility and function of young and non
      osteoarthritic patients whose previous surgical treatment of massive postero
      superior irreparable rotator cuff tear failed. As a primary procedure, latissimus
      dorsi tendon transfer competes with debridement, biceps tenotomy, and partial
      cuff repair. In association with reverse shoulder arthroplasty, it restores
      active external rotation in osteoarthritic patients with active external rotation
      deficit. New arthroscopic assisted techniques might improve results in the
      future. 

PMID- 24458943
TI  - Epidemiologic features of male genital malformations and subtypes in Texas.
AB  - Although distinct categories of male genital malformations share some common risk
      factors, few studies have systematically compared epidemiologic features across
      phenotypes. We evaluated the relationship between several maternal and infant
      characteristics and five categories of male genital malformations: second- or
      third-degree hypospadias, hypospadias (regardless of degree), small penis,
      cryptorchidism, and any male genital malformation. Data for 16,813 cases with
      isolated male genital malformations and 1,945,841 male live births delivered from
      1999 to 2008 were obtained from the Texas Birth Defects Registry. For each
      phenotype category, 13 maternal and infant variables were assessed, and adjusted
      prevalence ratios were estimated based on the same multivariable Poisson
      regression model. A significant negative association was observed between
      previous live births versus no previous live births and four phenotypes (e.g.,
      adjusted prevalence ratio [aPR] for any male genital malformation: 0.78, 95%
      confidence interval [CI]: 0.75-0.81). The prevalence of 4 of the phenotypes was
      significantly higher among multiple versus singleton pregnancies (e.g., aPR for
      any male genital malformation: 1.35, 95% CI: 1.25-1.47). We also observed
      significant associations between multiple phenotypes and residential region at
      delivery, delivery year, month of conception, and maternal age, race/ethnicity,
      education, and birthplace, including significant associations for trends
      (maternal age, maternal education, and birth year modeled ordinally). Our results
      allow for comparison of characteristics across phenotypes and suggest that there
      may be some common risk factors for multiple male genital malformations (e.g.,
      characteristics related to maternal estrogen levels), while other risk factors
      may be unique to specific defects.

PMID- 24458944
TI  - Treadmill training and body weight support for walking after stroke.
AB  - BACKGROUND: Treadmill training, with or without body weight support using a
      harness, is used in rehabilitation and might help to improve walking after
      stroke. This is an update of a Cochrane review first published in 2005.
      OBJECTIVES: To determine if treadmill training and body weight support,
      individually or in combination, improve walking ability, quality of life,
      activities of daily living, dependency or death, and institutionalisation or
      death, compared with other physiotherapy gait training interventions after
      stroke. The secondary objective was to determine the safety and acceptability of
      this method of gait training. SEARCH METHODS: We searched the Cochrane Stroke
      Group Trials Register (last searched June 2013), the Cochrane Central Register of
      Controlled Trials (CENTRAL) and the Database of Reviews of Effects (DARE) (The
      Cochrane Library 2013, Issue 7), MEDLINE (1966 to July 2013), EMBASE (1980 to
      July 2013), CINAHL (1982 to June 2013), AMED (1985 to July 2013) and SPORTDiscus
      (1949 to June 2013). We also handsearched relevant conference proceedings and
      ongoing trials and research registers, screened reference lists and contacted
      trialists to identify further trials. SELECTION CRITERIA: Randomised or quasi
      randomised controlled and cross-over trials of treadmill training and body weight
      support, individually or in combination, for the treatment of walking after
      stroke. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials,
      extracted data and assessed methodological quality. The primary outcomes
      investigated were walking speed, endurance and dependency. MAIN RESULTS: We
      included 44 trials with 2658 participants in this updated review. Overall, the
      use of treadmill training with body weight support did not increase the chances
      of walking independently compared with other physiotherapy interventions (risk
      difference (RD) -0.00, 95% confidence interval (CI) -0.02 to 0.02; P = 0.94; I2 =
      0%). Overall, the use of treadmill training with body weight support in walking
      rehabilitation for patients after stroke increased the walking velocity and
      walking endurance significantly. The pooled mean difference (MD) (random-effects
      model) for walking velocity was 0.07 m/s (95% CI 0.01 to 0.12; P = 0.02; I2 =
      57%) and the pooled MD for walking endurance was 26.35 metres (95% CI 2.51 to
      50.19; P = 0.03; I2 = 60%). Overall, the use of treadmill training with body
      weight support in walking rehabilitation for patients after stroke did not
      increase the walking velocity and walking endurance at the end of scheduled
      follow-up significantly. The pooled MD (random-effects model) for walking
      velocity was 0.04 m/s (95% CI -0.06 to 0.14; P = 0.40; I2 = 40%) and the pooled
      MD for walking endurance was 32.36 metres (95% CI -3.10 to 67.81; P = 0.07; I2 =
      63%). However, for ambulatory patients improvements in walking endurance lasted
      until the end of scheduled follow-up (MD 58.88 metres, 95% CI 29.10 to 88.66; P =
      0.0001; I2 = 0%). Adverse events and drop outs did not occur more frequently in
      people receiving treadmill training and these were not judged to be clinically
      serious events. AUTHORS' CONCLUSIONS: Overall, people after stroke who receive
      treadmill training with or without body weight support are not more likely to
      improve their ability to walk independently compared with people after stroke not
      receiving treadmill training, but walking speed and walking endurance may
      improve. Specifically, stroke patients who are able to walk (but not people who
      are not able to walk) appear to benefit most from this type of intervention. This
      review found that improvements in walking endurance in people able to walk may
      have persisting beneficial effects. Further research should specifically
      investigate the effects of different frequencies, durations or intensities (in
      terms of speed increments and inclination) of treadmill training, as well as the
      use of handrails, in ambulatory patients, but not in dependent walkers.

PMID- 24458945
TI  - Prenatal diagnosis of Carpenter syndrome: looking beyond craniosynostosis and
      polysyndactyly.
AB  - Carpenter syndrome is an autosomal recessive disorder comprising
      craniosynostosis, polysyndactyly, and brachydactyly. It occurs in approximately 1
      birth per million. We present a patient with Carpenter syndrome (confirmed by
      molecular diagnosis) who has several unique and previously unreported
      manifestations including a large ovarian cyst and heterotaxy with malrotation of
      stomach, intestine, and liver. These findings were first noted by prenatal
      ultrasound and may assist in prenatally diagnosing additional cases of Carpenter
      syndrome.

PMID- 24458946
TI  - Enzalutamide (Xtandi) for patients with metastatic, resistant prostate cancer.
AB  - OBJECTIVE: To review the pharmacology and pharmacokinetics, and to evaluate the
      clinical efficacy, safety, and place in therapy of enzalutamide for the treatment
      of castration-resistant prostate cancer (CRPC). DATA SOURCES: A literature search
      through PubMed (1984 to November 2013; English language) was performed using the
      following keywords: MDV3100, androgen deprivation therapy, enzalutamide, CRPC,
      and androgen receptor antagonist. Searches were limited to published studies in
      humans. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified
      from reviews, abstracts, presentations, and clinical trials of enzalutamide in
      humans were selected and included. DATA SYNTHESIS: Enzalutamide is an oral,
      nonsteroidal second-generation androgen receptor antagonist that is Food and Drug
      Administration-approved for the treatment of metastatic CRPC in men who were
      previously treated with docetaxel. Enzalutamide was superior to placebo for
      increasing median survival from 13.6 months to 18.4 months. Enzalutamide was well
      tolerated at a dose of 160 mg, with minor adverse events such as fatigue,
      diarrhea, musculoskeletal pain, and hot flashes. Patients with increased risk of
      seizure should not take enzalutamide. CONCLUSIONS: Enzalutamide is effective to
      slow progression of metastatic CRPC, to reduce prostate-specific antigen (PSA)
      levels, to decrease time to progression of PSA, to increase time to first
      skeletal-related events, and to increase quality of response rate. Enzalutamide
      was given at 160 mg/d for a median of 8 cycles of administration. Clinical trials
      are currently being conducted to observe if enzalutamide will be useful for
      treatment of other cancers and for early administration in prostate cancer.

PMID- 24458947
TI  - Comments on linezolid in morbid obesity.

PMID- 24458948
TI  - Macitentan for the treatment of pulmonary arterial hypertension.
AB  - OBJECTIVE: To review the pharmacology, safety, and efficacy of macitentan. DATA
      SOURCES: PubMed, EMBASE, and ClinicalTrials.gov were searched using the terms
      macitentan and ACT-064992. STUDY SELECTION AND DATA EXTRACTION: Phase II and III
      trials were reviewed in our primary analysis; data from phase I trials and other
      studies were reported as applicable. DATA SYNTHESIS: Macitentan is a dual
      endothelin receptor antagonist (ERA) approved for the treatment of pulmonary
      arterial hypertension (PAH). Current treatment options for PAH include 2 other
      ERAs, phosphodiesterase type 5 inhibitors, prostanoids, and calcium channel
      blockers. Recently published guidelines do not assert a preference for individual
      agents. Two trials evaluated the safety and efficacy of macitentan. The phase II
      study was a 12-month placebo-controlled trial involving patients with idiopathic
      pulmonary fibrosis; the primary end point was change in forced vital capacity. No
      significant treatment effect was observed. The phase III study was a placebo
      controlled trial involving patients with PAH. The primary end point was time to
      first occurrence of a composite of outcomes, including all-cause death and PAH
      worsening. Over a median period of 115 weeks, macitentan 10 mg and 3 mg daily
      significantly reduced morbidity and mortality. Commonly reported adverse effects
      included worsening of PAH, peripheral edema, upper-respiratory-tract infection,
      and anemia. CONCLUSIONS: Macitentan represents the latest addition to the PAH
      armamentarium. Compared with other ERAs, clinical advantages may include fewer
      contraindications, use in hepatic impairment, and once-daily administration.
      However, further comparative studies are necessary to ascertain its place in
      therapy.

PMID- 24458949
TI  - Adjustable thermoplastic mandibular advancement device for obstructive sleep
      apnea: outcomes and practicability.
AB  - OBJECTIVES/HYPOTHESIS: To assess outcomes including efficacy, adverse effects,
      and quality of life (QOL) of an adjustable thermoplastic mandibular advancement
      device (AT-MAD) fitted by an otolaryngologist for obstructive sleep apnea (OSA)
      treatment. STUDY DESIGN: Prospective, nonrandomized, before-after study. METHODS:
      Sixty-four adult patients (40 men and 24 women) were recruited. Inclusion
      criteria were OSA patients who had failed or refused treatment with continuous
      positive airway pressure and surgery. Exclusion criteria were insufficient teeth,
      active intraoral disease, and temporomandibular joint (TMJ) disorders. Outcomes
      were measured using polysomnography, symptom questionnaires, Epworth Sleepiness
      Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ) before
      treatment and 4 to 6 months thereafter. RESULTS: Mean apnea-hypopnea index (AHI)
      and ESS scores decreased from 17.7 +/- 14.6 to 7.5 +/- 10.9 and from 8.7 +/- 4.9
      to 6.5 +/- 4.4, respectively, after treatment (P < .001). Thirty-nine patients
      (60.9%) achieved post-treatment AHI of <5, with the highest success rate in those
      with mild OSA (75%). FOSQ global scores increased from 16.4 +/- 2.8 to 17.7 +/-
      3.0 (P < .05), along with most FOSQ subscale scores. Thirty-four patients (53.1%)
      regularly used the device for >=5 nights per week. Adverse effects include TMJ
      discomfort, dry mouth, and excessive salivation, which were largely tolerable.
      Only four patients withdrew from the study because of adverse effects.
      CONCLUSIONS: This is the first study in Asians demonstrating that an AT-MAD, if
      done properly, is a practical short-term treatment of OSA, with good outcomes
      including improved QOL. Its advantages are its low cost and ready-to-use nature.
      However, further randomized controlled trials are required.

PMID- 24458950
TI  - ngsTools: methods for population genetics analyses from next-generation
      sequencing data.
AB  - SUMMARY: Next-generation sequencing technologies produce short reads that are
      either de novo assembled or mapped to a reference genome. Genotypes and/or single
      nucleotide polymorphisms are then determined from the read composition at each
      site, which become the basis for many downstream analyses. However, for low
      sequencing depths, e.g. , there is considerable statistical uncertainty in the
      assignment of genotypes because of random sampling of homologous base pairs in
      heterozygotes and sequencing or alignment errors. Recently, several probabilistic
      methods have been proposed to account for this uncertainty and make accurate
      inferences from low quality and/or coverage sequencing data. We present ngsTools,
      a collection of programs to perform population genetics analyses from next
      generation sequencing data. The methods implemented in these programs do not rely
      on single-nucleotide polymorphism or genotype calling and are particularly
      suitable for low sequencing depth data. AVAILABILITY: Programs included in
      ngsTools are implemented in C/C++ and are freely available for noncommercial use
      at https://github.com/mfumagalli/ngsTools. CONTACT: mfumagalli82@gmail.com
      SUPPLEMENTARY INFORMATION: Supplementary materials are available at
      Bioinformatics online.

PMID- 24458951
TI  - The most informative spacing test effectively discovers biologically relevant
      outliers or multiple modes in expression.
AB  - SUMMARY: Several outlier and subgroup identification statistics (OASIS) have been
      proposed to discover transcriptomic features with outliers or multiple modes in
      expression that are indicative of distinct biological processes or subgroups.
      Here, we borrow ideas from the OASIS methods in the bioinformatics and statistics
      literature to develop the 'most informative spacing test' (MIST) for unsupervised
      detection of such transcriptomic features. In an example application involving 14
      cases of pediatric acute megakaryoblastic leukemia, MIST more robustly identified
      features that perfectly discriminate subjects according to gender or the presence
      of a prognostically relevant fusion-gene than did seven other OASIS methods in
      the analysis of RNA-seq exon expression, RNA-seq exon junction expression and
      micorarray exon expression data. MIST was also effective at identifying features
      related to gender or molecular subtype in an example application involving 157
      adult cases of acute myeloid leukemia. AVAILABILITY: MIST will be freely
      available in the OASIS R package at
      http://www.stjuderesearch.org/site/depts/biostats CONTACT:
      stanley.pounds@stjude.org SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 24458952
TI  - Algorithms and tools for protein-protein interaction networks clustering, with a
      special focus on population-based stochastic methods.
AB  - MOTIVATION: Protein-protein interaction (PPI) networks are powerful models to
      represent the pairwise protein interactions of the organisms. Clustering PPI
      networks can be useful for isolating groups of interacting proteins that
      participate in the same biological processes or that perform together specific
      biological functions. Evolutionary orthologies can be inferred this way, as well
      as functions and properties of yet uncharacterized proteins. RESULTS: We present
      an overview of the main state-of-the-art clustering methods that have been
      applied to PPI networks over the past decade. We distinguish five specific
      categories of approaches, describe and compare their main features and then focus
      on one of them, i.e. population-based stochastic search. We provide an
      experimental evaluation, based on some validation measures widely used in the
      literature, of techniques in this class, that are as yet less explored than the
      others. In particular, we study how the capability of Genetic Algorithms (GAs) to
      extract clusters in PPI networks varies when different topology-based fitness
      functions are used, and we compare GAs with the main techniques in the other
      categories. The experimental campaign shows that predictions returned by GAs are
      often more accurate than those produced by the contestant methods. Interesting
      issues still remain open about possible generalizations of GAs allowing for
      cluster overlapping. AVAILABILITY AND IMPLEMENTATION: We point out which methods
      and tools described here are publicly available. CONTACT:
      simona.rombo@math.unipa.it SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 24458953
TI  - Predictors of change in carotid atherosclerotic plaque inflammation and burden as
      measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study.
AB  - Baseline predictors of response to treatment of patients with coronary heart
      disease (CHD) with respect to vascular inflammation and atherosclerotic plaque
      burden are poorly understood. From post hoc analysis of the dal-PLAQUE study
      (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET)
      imaging and carotid black blood magnetic resonance imaging (MRI) were used to
      track changes in these vascular parameters. Baseline demographics, imaging, and
      biomarkers were collected/measured in 130 patients with CHD or CHD risk
      equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was
      performed. Using stepwise linear regression, predictors of change in carotid
      plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque
      burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were
      determined. Variables with p < 0.05 in multivariable models were considered
      independently significant. Interleukin-6, systolic blood pressure and standard
      deviation of wall thickness (WT) at baseline were independently positively
      associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6
      months). Mean of mean TBR, phospholipase A2, apolipoprotein A-I, and high
      sensitivity C-reactive protein at baseline were independently negatively
      associated with MeanMax TBR change over 6 months. Mean WT and plasminogen
      activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently
      associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1
      activity at baseline, age, and female gender were independent predictors. These
      findings may help determine patients most suitable for clinical trials employing
      plaque inflammation or burden changes as endpoints.

PMID- 24458954
TI  - Implications of a bioresorbable vascular scaffold implantation on vessel wall
      strain of the treated and the adjacent segments.
AB  - BACKGROUND: Metallic stents change permanently the mechanical properties of the
      vessel wall. However little is known about the implications of bioresorbable
      vascular scaffolds (BVS) on the vessel wall strain. METHODS: Patients (n = 53)
      implanted with an Absorb BVS that had palpographic evaluation at any time point
      [before device implantation, immediate after treatment, at short-term (6-12
      months) or mid-term follow-up (24-36 months)] were included in the current
      analysis. The palpographic data were used to estimate the mean of the maximum
      strain values and the obtained measurements were classified using the Rotterdam
      classification (ROC) score and expressed as ROC/mm. RESULTS: Scaffold
      implantation led to a significant decrease of the vessel wall strain in the
      treated segment [0.35 (0.20, 0.38) vs. 0.19 (0.09, 0.29); P = 0.005] but it did
      not affect the proximal and distal edge. In patients who had serial palpographic
      examination the vessel wall strain continued to decrease in the scaffolded
      segment at short-term [0.20 (0.12, 0.29) vs. 0.14 (0.08, 0.20); P = 0.048] and
      mid-term follow-up [0.20 (0.12, 0.29) vs. 0.15 (0.10, 0.19), P = 0.024]. No
      changes were noted with time in the mechanical properties of the vessel wall at
      the proximal and distal edge. CONCLUSIONS: Absorb BVS implantation results in a
      permanent alteration of the mechanical properties of the vessel wall in the
      treated segment. Long term follow-up data are needed in order to examine the
      clinical implications of these findings.

PMID- 24458955
TI  - Fusion of optical coherence tomographic and angiographic data for more accurate
      evaluation of the endothelial shear stress patterns and neointimal distribution
      after bioresorbable scaffold implantation: comparison with intravascular
      ultrasound-derived reconstructions.
AB  - Intravascular ultrasound (IVUS)-based reconstructions have been traditionally
      used to examine the effect of endothelial shear stress (ESS) on neointimal
      formation. The aim of this analysis is to compare the association between ESS and
      neointimal thickness (NT) in models obtained by the fusion of optical coherence
      tomography (OCT) and coronary angiography and in the reconstructions derived by
      the integration of IVUS and coronary angiography. We analyzed data from six
      patients implanted with an Absorb bioresorbable vascular scaffold that had
      biplane angiography, IVUS and OCT investigation at baseline and 6 or 12 months
      follow-up. The IVUS and OCT follow-up data were fused separately with the
      angiographic data to reconstruct the luminal morphology at baseline and follow
      up. Blood flow simulation was performed on the baseline reconstructions and the
      ESS was related to NT. In the OCT-based reconstructions the ESS were lower
      compared to the IVUS-based models (1.29 +/- 0.66 vs. 1.87 +/- 0.66 Pa, P =
      0.030). An inverse correlation was noted between the logarithmic transformed ESS
      and the measured NT in all the OCT-based models which was higher than the
      correlation reported in five of the six IVUS-derived models (-0.52 +/- 0.19 Pa
      vs. -0.10 +/- 0.04, P = 0.028). Fusion of OCT and coronary angiography appears
      superior to IVUS-based reconstructions; therefore it should be the method of
      choice for the study of the effect of the ESS on neointimal proliferation.

PMID- 24458956
TI  - Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent
      malignant glioma.
AB  - Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions
      regarding the lack of an overall survival benefit, the optimal timing in the
      disease course and potential combination and salvage therapies. We
      retrospectively assessed survival, radiological progression type on bevacizumab
      and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas
      who received bevacizumab and nitrosourea sequentially. 15 patients received
      bevacizumab followed by nitrosourea at progression and 27 patients vice versa.
      Time to treatment failure, defined as time from initiation of one to failure of
      the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p =
      0.19). Progression-free survival on nitrosoureas was comparable in both groups,
      while progression-free survival on bevacizumab was longer in the group receiving
      bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were
      similar for patients with grade III (n = 9) and grade IV (n = 33) tumors.
      Progression-free survival on bevacizumab for patients developing contrast
      enhancing T1 progression was longer than for patients who displayed a non
      enhancing T2 progression. However, post-progression survival times after
      bevacizumab failure were not different. Earlier treatment with bevacizumab was
      not associated with better outcome in this series. The fact that earlier as
      compared to later bevacizumab treatment does not result in a different time to
      treatment failure highlights the challenge for first-line or recurrence trials
      with bevacizumab to demonstrate an overall survival benefit if crossover of
      bevacizumab-naive patients after progression occurs.

PMID- 24458957
TI  - High HDL cholesterol level after treatment with pitavastatin is an important
      factor for regression in carotid intima-media thickness.
AB  - This study is a prospective multicenter study designed to investigate the effects
      of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients
      with coronary heart disease, and to determine which factor is more closely
      associated with plaque regression. Participants (n = 63) were treated with
      pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was
      measured by ultrasound before and after treatment. Mean IMT slightly but
      significantly decreased (from 0.99 +/- 0.33 to 0.94 +/- 0.28 mm for overall, P =
      0.01) regardless of the presence of pretreatment with other statins. There were
      no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and
      smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases
      in mean IMT were observed significantly more frequently in subjects with high on
      treatment HDL cholesterol levels than with low HDL cholesterol levels (P =
      0.017). The change in mean IMT tended to be inversely correlated with increments
      in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often
      observed in the absence of diabetes and metabolic syndrome. In conclusion, we
      demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque.
      This effect was associated with the level of HDL cholesterol, and was stronger in
      the absence of diabetes and metabolic syndrome in our ischemic heart disease
      patients.

PMID- 24458958
TI  - Traumatic brain injury, posttraumatic stress disorder, and pain diagnoses in
      OIF/OEF/OND Veterans.
AB  - To identify the prevalence of traumatic brain injury (TBI), posttraumatic stress
      disorder (PTSD), and pain in Veterans from Operation Iraqi Freedom/Operation
      Enduring Freedom/Operation New Dawn (OIF/OEF/OND), Veterans who received any
      inpatient or outpatient care from Veterans Health Administration (VHA) facilities
      from 2009 to 2011 were studied. A subset of Veterans was identified who were
      diagnosed with TBI, PTSD, and/or pain (head, neck, or back) as determined by
      their International Classification of Diseases-9th Revision-Clinical Modification
      codes. Between fiscal years 2009 and 2011, 613,391 Veterans accessed VHA services
      at least once (age: 31.9 +/- 9.6 yr). TBI diagnosis in any 1 year was slightly
      less than 7%. When data from 3 years were pooled, 9.6% were diagnosed with TBI,
      29.3% were diagnosed with PTSD, and 40.2% were diagnosed with pain. The full
      polytrauma triad expression (TBI, PTSD, and pain) was diagnosed in 6.0%. Results
      show that increasing numbers of Veterans from OIF/OEF/OND accessed VHA over a 3
      year period. Among those with a TBI diagnosis, the majority also had a mental
      health disorder, with approximately half having both PTSD and pain. While the
      absolute number of Veterans increased by over 40% from 2009 to 2011, the
      proportion of Veterans diagnosed with TBI and the high rate of comorbid PTSD and
      pain in this population remained relatively stable. 

PMID- 24458959
TI  - Association of vitamin D deficiency, secondary hyperparathyroidism, and
      heterotopic ossification in spinal cord injury.
AB  - Our objective was to explore the relationship between low vitamin D, secondary
      hyperparathyroidism, and heterotopic ossification (HO) in patients with spinal
      cord injury (SCI). Ninety-six subjects with acute or chronic motor complete SCI
      participated. Levels of serum vitamin D25(OH), calcium, and intact parathyroid
      hormone (PTH) were collected, and information regarding nutritional patterns and
      fracture history was obtained from subjects. Evidence of current or previous HO
      was ascertained through chart review. Of the 96 subjects, 12 were found to have
      developed HO, 11 with serum vitamin D25(OH) between 5 and 17 ng/mL. Nine subjects
      exhibited secondary hyperparathyroidism in the range of 72 to 169 pg/mL. Only one
      subject demonstrated HO in the absence of low vitamin D. However, many subjects
      with low vitamin D (5-31 ng/mL) did not have hyperparathyroidism or HO.
      Statistical testing demonstrated a correlation between hyperparathyroidism and HO
      (p < 0.001) as well as hyperparathyroidism and vitamin D deficiency (<20 ng/mL).
      Direct correlation between HO and low vitamin D was not observed, but
      hyperparathyroidism may increase this risk. We believe that those patients who
      demonstrate low vitamin D and elevated PTH should be screened for HO in addition
      to beginning vitamin supplementation. Initiating early treatment of low vitamin D
      to restore therapeutic levels may prevent development of HO. 

PMID- 24458960
TI  - Size of kinematic error affects retention of locomotor adaptation in human spinal
      cord injury.
AB  - Studies in arm motor adaptation suggest that introducing small errors during the
      adaptation period may lead to a longer retention of the aftereffect than
      introducing large errors. However, it is unclear whether this notion can be
      generalized to locomotor adaptation in patients with incomplete spinal cord
      injury (SCI). We hypothesized that a smaller error size may lead to longer
      retention of the aftereffect in patients with SCI. We recruited 12 subjects with
      incomplete SCI for this study. They were instructed to walk on a treadmill while
      light-, medium-, and heavy-resistance loads were applied to the right ankle to
      perturb leg swing. Each of the three resistance-load conditions were specific to
      the subject and determined by each subject's maximum voluntary contraction of the
      hip flexors. We observed that subjects tended to make larger errors when the
      resistance-load condition was greater. Following resistance load release,
      subjects showed an aftereffect consisting of an increase in stride length.
      Further, the aftereffect was retained longer in the medium-resistance load
      condition than in the heavy- and light-resistance load conditions. This finding
      suggests that a patient-specific resistance load may be needed to facilitate
      retention of locomotor adaptation in patients with incomplete SCI. 

PMID- 24458961
TI  - Classifying prosthetic use via accelerometry in persons with transtibial
      amputations.
AB  - Knowledge of how persons with amputation use their prostheses and how this use
      changes over time may facilitate effective rehabilitation practices and enhance
      understanding of prosthesis functionality. Perpetual monitoring and
      classification of prosthesis use may also increase the health and quality of life
      for prosthetic users. Existing monitoring and classification systems are often
      limited in that they require the subject to manipulate the sensor (e.g., attach,
      remove, or reset a sensor), record data over relatively short time periods,
      and/or classify a limited number of activities and body postures of interest. In
      this study, a commercially available three-axis accelerometer (ActiLife ActiGraph
      GT3X+) was used to characterize the activities and body postures of individuals
      with transtibial amputation. Accelerometers were mounted on prosthetic pylons of
      10 persons with transtibial amputation as they performed a preset routine of
      actions. Accelerometer data was postprocessed using a binary decision tree to
      identify when the prosthesis was being worn and to classify periods of use as
      movement (i.e., leg motion such as walking or stair climbing), standing (i.e.,
      standing upright with limited leg motion), or sitting (i.e., seated with limited
      leg motion). Classifications were compared to visual observation by study
      researchers. The classifier achieved a mean +/- standard deviation accuracy of
      96.6% +/- 3.0%.

PMID- 24458962
TI  - Upper-limb activity in adults: referent values using accelerometry.
AB  - The goal of physical rehabilitation following upper-limb (UL) impairment is
      functional restoration of the UL for use in daily activities. Because capacity
      for UL function may not translate into real-world activity, it is important that
      assessment of real-world UL activity be used in conjunction with clinical
      measures of capacity. Accelerometry can be used to quantify duration of UL
      activity outside of the clinic. The purpose of this study was to characterize
      hours of UL activity and potential modifying factors of UL activity (sedentary
      activity, cognitive impairment, depressive symptomatology, additive effects of
      comorbidities, cohabitation status, and age). Seventy-four community-dwelling
      adults wore accelerometers on bilateral wrists for 25 h and provided information
      on modifying factors. Mean time of dominant UL activity was 9.1 +/- 1.9 h, and
      the ratio of activity between the nondominant and dominant ULs was 0.95 +/- 0.06
      h. Decreased hours of dominant UL activity was associated with increased time
      spent in sedentary activity. No other factors were associated with hours of
      dominant UL activity. These data can be used to help clinicians establish outcome
      goals for patients given preimpairment level of sedentary activity and to track
      progress during rehabilitation of the ULs.

PMID- 24458963
TI  - Effect of oculomotor rehabilitation on vergence responsivity in mild traumatic
      brain injury.
AB  - A range of dynamic and static vergence responses were evaluated in 12 individuals
      with mild traumatic brain injury (age: 29 +/- 3 yr) having near vision symptoms.
      All measures were performed in a crossover design before and after oculomotor
      training (OMT) and placebo (P) training. Following OMT, peak velocity for both
      convergence and divergence increased significantly. Increased peak velocity was
      significantly correlated with increased clinically based vergence prism flipper
      rate. Steady-state response variability for convergence reduced significantly
      following OMT. The maximum amplitude of convergence, relative fusional
      amplitudes, and near stereoacuity improved significantly. In addition, symptoms
      reduced significantly, and visual attention improved markedly. None of the
      measures were found to change significantly following P training. The significant
      improvement in most aspects of vergence eye movements following OMT demonstrates
      considerable residual brain plasticity via oculomotor learning. The improved
      vergence affected positively on nearwork-related symptoms and visual attention. 

PMID- 24458964
TI  - Transfemoral sockets with vacuum-assisted suspension comparison of hip
      kinematics, socket position, contact pressure, and preference: ischial
      containment versus brimless.
AB  - The objective of this study was to investigate the effect of brimless compared
      with ischial ramus containment (IRC) prosthetic sockets when using vacuum
      assisted suspension (VAS) on persons with a unilateral transfemoral amputation
      (TFA). A randomized crossover design with a 2 d accommodation was used. People
      with unilateral TFA (n = 9 analyzed) were enrolled. Interventions were IRC VAS
      and brimless VAS sockets. Main outcome measures included coronal hip angle and
      vertical and lateral socket movement as measured by X-ray, skin pressure measured
      by Tekscan, and preference measured subjectively. The brimless design was
      statistically equivalent to IRC in all measured coronal hip angles and vertical
      and lateral socket displacement. The peak/stance mean pressure in the medial
      proximal aspect of the socket was 322 mmHg in the IRC compared with 190 mmHg in
      the brimless condition. Except for medial proximal pressure, no other measures
      reached statistical significance. All subjects reported the brimless design to be
      more comfortable than the IRC in short-term preference. Brimless VAS socket
      design may be a clinically viable choice for people with TFA. 

PMID- 24458965
TI  - Design and evaluation of two different finger concepts for body-powered
      prosthetic hand.
AB  - The goal of this study was to find an efficient method of energy transmission for
      application in an anthropomorphic underactuated body-powered (BP) prosthetic
      hand. A pulley-cable finger and a hydraulic cylinder finger were designed and
      tested to compare the pulley-cable transmission principle with the hydraulic
      cylinder transmission principle. Both fingers had identical dimensions and a low
      mass. The only thing that differed between the fingers was the transmission
      principle. The input energy was measured for a number of tasks. The pulley-cable
      finger required more input energy than the hydraulic cylinder finger to perform
      the tasks. This was especially the case in tasks that required high pinch forces.
      The hydraulic cylinder transmission is therefore the more efficient transmission
      for application in BP prosthetic fingers. 

PMID- 24458966
TI  - Determinants of postsurgical discharge setting for male hip fracture patients.
AB  - Veterans hospitalized for hip fracture repair may be discharged to one of several
      rehabilitation settings, but it is not known what factors influence postsurgical
      discharge setting. The purpose of the study was to examine the patient, facility,
      and market factors that influence the choice of postsurgical discharge setting.
      Using a retrospective cohort design, we linked 11,083 veterans who had hip
      fracture surgeries in a Department of Veterans Affairs (VA) hospital from 1998 to
      2005 as assessed by the VA National Surgical Quality Improvement Program dataset
      with administrative data. The factors associated with five postdischarge settings
      were analyzed using multinomial logistic regression. We found that few veterans
      (0.8%) hospitalized for hip fracture were discharged with home health. Higher
      proportions of veterans were discharged to a nursing home (15.4%), to outpatient
      rehabilitation (18.8%), to inpatient rehabilitation (16.9%), or to home (48.2%).
      Patients were more likely to be discharged to nonhome settings for VA-provided
      rehabilitation if they had total function dependence, had American Society of
      Anesthesiologists class 4 or 5, had surgical complications prior to discharge, or
      lived in counties with lower nursing home bed occupancy rates. Future research
      should compare postsurgical and longer-term morbidity, mortality, and healthcare
      utilization across these rehabilitation settings. 

PMID- 24458967
TI  - Circumstances and consequences of falls among people with chronic stroke.
AB  - Falls are common after stroke; however, circumstances and consequences are
      relatively unknown. Our objectives were to identify the differences between
      fallers and non-fallers among people with chronic stroke, identify the
      circumstances of fall events, and examine the consequences of the falls. This is
      a secondary data analysis; all participants included sustained a stroke.
      Variables included demographics, stroke characteristics, and comorbidities. Falls
      were collected via self-report, and circumstances and consequences were derived
      from participant description of the event and categorized as appropriate. Among
      160 participants, 53 (33%) reported a fall during the 1 yr period. Circumstances
      of falls were categorized as intrinsic or extrinsic. Location and circumstance of
      the fall were included: 70% occurred at home and 40% were associated with
      impaired physical or mental state (e.g., inattention to tying shoes).
      Additionally, 21% of falls were associated with activities of daily living and
      mobility and 34% with slips or trips. The majority who fell sustained an injury
      (72%). Injuries ranged from bruising to fractures, and 55% of those with an
      injury sought medical care (32% to emergency department). Poststroke falls are
      associated with an alarming rate of injury and healthcare utilization. Targeting
      mental and physical states may be key to fall prevention. 

PMID- 24458968
TI  - Power mobility with collision avoidance for older adults: user, caregiver, and
      prescriber perspectives.
AB  - Collision avoidance technology has the capacity to facilitate safer mobility
      among older power mobility users with physical, sensory, and cognitive
      impairments, thus enabling independence for more users. Little is known about
      consumers' perceptions of collision avoidance. This article draws on interviews
      (29 users, 5 caregivers, and 10 prescribers) to examine views on design and
      utilization of this technology. Data analysis identified three themes: "useful
      situations or contexts," "technology design issues and real-life application,"
      and "appropriateness of collision avoidance technology for a variety of users."
      Findings support ongoing development of collision avoidance for older adult
      users. The majority of participants supported the technology and felt that it
      might benefit current users and users with visual impairments, but might be
      unsuitable for people with significant cognitive impairments. Some participants
      voiced concerns regarding the risk for injury with power mobility use and some
      identified situations where collision avoidance might be beneficial (driving
      backward, avoiding dynamic obstacles, negotiating outdoor barriers, and learning
      power mobility use). Design issues include the need for context awareness,
      reliability, and user interface specifications. User desire to maintain driving
      autonomy supports development of collaboratively controlled systems. This
      research lays the groundwork for future development by illustrating consumer
      requirements for this technology. 

PMID- 24458969
TI  - Depression and experience of vision loss in group of adults in rehabilitation
      setting: mixed-methods pilot study.
AB  - There is a paucity of literature regarding the relationship between the
      experience of vision loss and depression. Therefore, the current pilot study
      aimed to explore whether significant differences existed in levels of depression
      between adults with different vision loss experiences. A group of adults aged
      between 20 and 65 yr old with irreversible vision loss in a rehabilitation
      setting was interviewed. Semistructured interviews were conducted in order to
      explore patients' experience of vision loss. The Center for Epidemiologic Studies
      Depression Scale (CES-D) was used to assess depressive levels; 39.5% (n = 15) of
      patients met CES-D criteria for depression. In addition, higher levels of
      depression (p < 0.05) were identified in patients whose interviews revealed
      greater self-awareness of impairment, inadequate social support, and longer
      rehabilitation stay. Current findings draw attention to variables such as self
      awareness of impairment and perceived social support and suggest that depression
      following vision loss may be related to patients' emotional experiences of
      impairment and adjustment processes. 

PMID- 24458970
TI  - Rebuttal to Ickmans et al. association between cognitive performance, physical
      fitness, and physical activity level in women with chronic fatigue syndrome. J
      Rehabil Res Dev. 2013;50(6):795-810. www.rehab.research.va.gov/jour/
      2013/506/pdf/ickmans506.pdf.

PMID- 24458971
TI  - Response.

PMID- 24458972
TI  - National prevalence of traumatic brain injury, posttraumatic stress disorder, and
      pain diagnoses in OIF/OEF/OND Veterans from 2009 to 2011.

PMID- 24458974
TI  - Addition of pluronics(r) to reducible disulfide-bond-containing Pluronic(r)-PEI
      SS specifically enhances circulation time in vivo and transfection efficiency in
      vitro.
AB  - To improve the circulation time and transfection efficiency of the polyplexes
      used in gene delivery, a series of Pluronic(r)/Pluronic(r)F127-PEI-SS/pDNA
      complexes (PFPS/pDNA), based on the addition of different kinds of Pluronics(r)
      to the reducible disulfide-bonds-containing Pluronic(r)F127-PEI-SS/pDNA
      (FPS/pDNA) polyplexes, was prepared and evaluated in Bcap and Hela cells in vitro
      and in vivo. The addition of Pluronics(r) with molecular weights and hydrophilic
      lipophilic balance (HLBs) different from that in the FPS/pDNA complex resulted in
      five PFPS(1-5)/pDNA complexes, and the correlation between the structure of the
      free Pluronic(r) and the properties of the PFPS/pDNA complexes was investigated.
      The addition of Pluronics(r) resulted in slightly larger or same-sized
      nanoparticles of PFPS/pDNA at a constant N/P ratio. The PFPS copolymer displayed
      strong stability against DNase I digestion and serum degradation. PFPS-4
      containing added Pluronic(r) L35, with an intermediate HLB of 19, showed a much
      higher transfection efficiency and less cytotoxicity than FPS or PEI-25 kDa in
      vitro. PFPS-4 also exhibited a considerably longer blood circulation time than
      FPS or PEI-25 kDa in vivo in mice, indicating that the addition of an
      intermediate Pluronic(r) can enhance the transfection efficiency of gene delivery
      systems.

PMID- 24458973
TI  - 3-substituted indazoles as configurationally locked 4EGI-1 mimetics and
      inhibitors of the eIF4E/eIF4G interaction.
AB  - 4EGI-1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a
      high-throughput screening of small-molecule libraries with the aid of a
      fluorescence polarization assay that measures inhibition of binding of an eIF4G
      derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI-1 has
      potential for the study of molecular mechanisms involved in human disorders
      characterized by loss of physiological restraints on translation initiation. A
      hit-to-lead optimization campaign was carried out to overcome the configurational
      instability in 4EGI-1, which stems from the E-to-Z isomerization of the hydrazone
      function. We identified compound 1 a, in which the labile hydrazone was
      incorporated into a rigid indazole scaffold, as a promising rigidified 4EGI-1
      mimetic lead. In a structure-activity relationship study directed towards probing
      the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G
      interaction and translation initiation we identified 1 d, an indazole-based 4EGI
      1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a
      promising molecular probe candidate for elucidation of the role of cap-dependent
      translation initiation in a host of pathophysiological states.

PMID- 24458975
TI  - Glycogen storage in the human retinal pigment epithelium: a comparative study of
      diabetic and non-diabetic donors.
AB  - Liver and muscle glycogen content is reduced in diabetic patients but there is no
      information on the effect of diabetes on the glycogen content in the retinal
      pigment epithelium (RPE). The main aim of the study was to compare the glycogen
      content in the RPE between diabetic and non-diabetic human donors. Glycogen
      synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen
      metabolism, as well as their isoforms, were also assessed. For this purpose, 44
      human postmortem eye cups were included (22 from 11 type 2 diabetic and 22 from
      11 non-diabetic donors matched by age). Human RPE cells cultured in normoglycemic
      and hyperglycemic conditions were also analyzed. Glycogen content as well as the
      mRNA, protein content and enzyme activity of GS and GP were determined. In
      addition, GS and GP isoforms were characterized. In the RPE from diabetic donors,
      as well as in RPE cells grown in hyperglycemic conditions, the glycogen content
      was increased. The increase in glycogen content was associated with an increase
      in GS without changes in GP levels. In RPE form human donors, the muscle GS
      isoform but not the liver GS isoform was detected. Regarding GP, the muscle and
      brain isoform of GP but not the liver GP isoform were detected. We conclude that
      glycogen storage is increased in the RPE of diabetic patients, and it is
      associated with an increase in GS activity. Further studies aimed at determining
      the role of glycogen deposits in the pathogenesis of diabetic retinopathy are
      warranted. 

PMID- 24458976
TI  - Designing cyclometalated ruthenium(II) complexes for anodic
      electropolymerization.
AB  - The anodic electropolymerization of thiophene-functionalized cyclometalated
      ruthenium(II) complexes is shown for the first time. Oxidative decomposition
      reactions can be overcome by modification of the involved redox potentials
      through the introduction of electron-withdrawing substituents, namely nitro
      groups, at the cyclometalating phenyl ring. The generated functionalized
      ruthenium(II) complexes allow the electrochemical preparation of thin polymer
      films, which show a broad UV/Vis absorption as well as reversible redox
      switchability. The presented complexes are promising candidates for future
      photovoltaic applications based on photo-redox-active films. 

PMID- 24458978
TI  - Data sharing in research: benefits and risks for clinicians.

PMID- 24458977
TI  - Fennel and raspberry leaf as possible inhibitors of acetaminophen oxidation.
AB  - In addition to CYP2E1, several CYP isoenzymes, notably CYP1A2, 2D6, and 3A4, are
      suggested to contribute in acetaminophen oxidation and formation of the
      hepatotoxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The in vitro CYP2E1
      inhibitory potentials of fennel and raspberry leaf, herbs previously found to
      inhibit CYP1A2, 2D6, and 3A4 activities in vitro, were investigated. Extracts
      from commercially available herbal products were incubated with recombinant cDNA
      expressed human CYP2E1. A validated LC/MS/MS methodology was applied for
      determination of 6-hydroxychlorzoxazone formation with disulfiram used as a
      positive inhibitory control. CYP2E1 IC50 inhibition constants were found to be 23
      +/- 4 and 27 +/- 5 ug/ml for fennel and raspberry leaf, respectively, constants
      significantly lower than those presented in the literature for other herbal
      extracts. Together with previous findings, the presented in vitro data for CYP2E1
      inhibition suggest that fennel and raspberry leaf have a significant potential of
      inhibiting all the major metabolic pathways for acetaminophen oxidation and NAPQI
      formation. Both herbs should be further investigated for their in vivo ability of
      inhibiting acetaminophen oxidation and NAPQI formation.

PMID- 24458979
TI  - A fifth of England's hospitals are likely to be in deficit, says King's Fund.

PMID- 24458980
TI  - Private sector may take elective patients in event of crisis in hospital
      emergency units, says NHS chief.

PMID- 24458981
TI  - Psychiatrist is suspended for another 12 months after showing no reflection or
      remediation.

PMID- 24458982
TI  - VEGF increases paracellular permeability in brain endothelial cells via
      upregulation of EphA2.
AB  - Neurological disorders are associated with an increase in the permeability of
      human brain microvascular endothelial cells (HBMEC). Our previous findings have
      indicated that EphA2 could increase the permeability of HBMEC. Recent evidence
      has linked EphA2 and vascular endothelial growth factor (VEGF) to abnormalities
      in the vascular response. However, it is unclear whether EphA2 is involved in the
      VEGF-induced changes in the permeability of HBMEC. Here, changes in permeability
      were determined by measuring transendothelial electrical resistance (TEER) and
      the flux of FITC-dextran. We found that knockdown of EphA2 in HBMEC abolished the
      VEGF-induced reduction in TEER and increase in flux of fluorescent dextran.
      Moreover, VEGF-induced redistribution of ZO-1 and the recruitment of detergent
      soluble occludin and claudin-5 were also prevented. Further results showed that
      VEGF increased EphA2 expression in a time- and dose-dependent manner, which was
      inhibited by a neutralizing antibody against VEGFR2 or SU1498. VEGF-induced EphA2
      expression was suppressed in the brain endothelium following treatments with the
      PI3K inhibitor LY294002, Akt inhibitor or transfection with the dominant-negative
      PI3K mutants (Deltap110). Similar results were obtained when ERK1/2 activation
      was inhibited by PD98059 or ERK1/2 siRNA transfection. Our data suggest that VEGF
      upregulates the expression of EphA2 in HBMEC through binding to VEGFR2 and
      subsequently activating the intracellular PI3K/Akt and ERK1/2 signaling pathways,
      which contribute to an increase in paracellular permeability. These data reveal a
      novel role for VEGF as a regulator of EphA2 expression in the brain endothelial
      cells and provide insights into the molecular mechanisms of VEGF-mediated changes
      in paracellular permeability.

PMID- 24458983
TI  - Keutel syndrome: report of two novel MGP mutations and discussion of clinical
      overlap with arylsulfatase E deficiency and relapsing polychondritis.
AB  - Keutel syndrome is a rare, autosomal recessive disorder characterized by diffuse
      cartilage calcification, peripheral pulmonary artery stenosis, midface retrusion,
      and short distal phalanges. To date, 28 patients from 18 families have been
      reported, and five mutations in the matrix Gla protein gene (MGP) have been
      identified. The matrix Gla protein (MGP) is a vitamin K-dependent extracellular
      protein that functions as a calcification inhibitor through incompletely
      understood mechanisms. We present the clinical manifestations of three affected
      siblings from a consanguineous Turkish family, in whom we detected the sixth MGP
      mutation (c.79G>T, which predicts p.E27X) and a fourth unrelated patient in whom
      we detected the seventh MGP mutation, a partial deletion of exon 4. Both
      mutations predict complete loss of MGP function. One of the patients presented
      initially with a working diagnosis of relapsing polychondritis. Clinical features
      suggestive of Keutel syndrome were also observed in one additional unrelated
      patient who was later found to have a deletion of arylsulfatase E, consistent
      with a diagnosis of X-linked recessive chondrodysplasia punctata. Through a
      discussion of these cases, we highlight the clinical overlap of Keutel syndrome,
      X-linked chondrodysplasia punctata, and the inflammatory disease relapsing
      polychondritis.

PMID- 24458984
TI  - TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2
      interstitial deletion.
AB  - Interstitial deletion of 2q24.2 is a rarely described cytogenetic aberration in
      patients with intellectual disability (ID). Previously reported genotype
      phenotype correlation identified a minimum deleted region of 2.65 Mb including 15
      genes. Recently, a patient with a de novo 2q24.2 microdeletion of 0.4 Mb
      encompassing only three genes was described. However, the precise relationship
      between most deleted genes and the clinical features remains unclear. Here we
      describe a 12-year-old male patient diagnosed with growth retardation and ID. He
      also showed microcephaly, right palpebral ptosis, scapular winging, and pectus
      excavatum. Single nucleotide polymorphisms (SNP) array analysis showed a de novo
      interstitial deletion of 0.122 Mb at 2q24.2 region harboring only TBR1 (T-box,
      brain, 1; OMIM: 604616), which encodes a T-box family transcription factor
      expressed in post-mitotic projection neurons and functionally significant in
      embryologic corticogenesis. This is the first case of a deletion at 2q24.2
      involving only TBR1. This finding narrows the smallest region of overlap (SRO)
      for deletions in this region and strengthens the previously suggested hypothesis
      that this gene is a strong candidate for the ID phenotype. The identification of
      TBR1 as candidate for ID encourages further molecular studies to identify novel
      mutations to understand the pathogenic effects of its haploinsufficiency.
      Finally, this report provides a review on 10 2q24.2 microdeletion patients.

PMID- 24458985
TI  - 14-Deoxy-11,12-didehydroandrographolide inhibits proliferation and induces GSH
      dependent cell death of human promonocytic leukemic cells.
AB  - 14-Deoxy-11,12-didehydroandrographolide (AND2), an analogue of andrographolide,
      showed more potent cytotoxicity against human promonocytic leukemia (THP-1) cells
      than adherent cancer cell lines. In this study AND2 was isolated from the plant
      Andrographis paniculata and it was characterized. The antiproliferative effect of
      AND2 on both adherent (PC-3 and MDAMB) and non-adherent (THP-1 and Jurkat) cancer
      cell lines was evaluated by MTT assay. The effect of intracellular reduced
      glutathione (GSH) on AND2-induced cytotoxicity was studied by conducting cell
      viability assays on GSH-pretreated cells. The effect of AND2 on the redox status
      of THP-1 cells was determined by analyzing the endogenous reduced GSH content.
      Apoptosis induction was confirmed by DNA laddering assay and Western blot
      analysis using anti-caspase-3 protein antibody. AND2 showed antiproliferative
      action on both THP-1 and Jurkat cancer cell lines with low IC50 values.
      Cytotoxicity of AND2 was reversed by GSH pretreatment. AND2 treatment decreased
      the GSH content by 19.76 % (p < 0.001) in the THP-1 cancer cell line and reduced
      the cell clumping between the THP-1 cells. Expression of procaspase-3 varied in
      THP-1 cells during the time course of AND2 treatment. Procaspase-3 expression
      reached a maximum in treated cells at 32 h and was markedly reduced at 48 h but
      no procaspase-3 cleavage was observed. The obtained results suggest that AND2 is
      more effective against leukemia cells. AND2 induced a redox-mediated cell death
      in THP-1 cells. As AND2 temporarily increased the procaspase-3 expression during
      treatment, this study encourages the preclinical testing of AND2 against
      promonocytic leukemia cells in combination with small molecules that directly
      activate procaspase-3 to caspase-3.

PMID- 24458987
TI  - Connections and barriers between cells of Drosera tentacles in relation to their
      electrophysiology.
AB  - The extracellular space of tentacles of Drosera capensis L. is divided into two
      compartments by cuticular material between cells of an endodermoid layer and by
      the nonporous cuticle of the stalk and neck. The distal compartment includes the
      mucilaginous secretion as well as the free space of the secretory cap, since the
      cuticle covering the cap is perforated by numerous 0.05-0.3 MUm pores. The
      proximal compartment includes xylem and the intercellular space of the stalk. The
      existence of the endodermoid partition is consistent with the observation that
      action potentials recorded extracellularly from the head may be positive-going
      while those recorded extracellularly from the stalk are negative-going. The
      partitioning is also consistent with the hypothesis previously proposed to
      explain why the amplitude of action potentials recorded from the mucilage varies
      as a function of the amplitude of the receptor potential.The living cells are
      united by plasmodesmata. Unusually abundant plasmodesmata were observed in the
      walls between endodermoid cells and neck cells, between neck cells and the next
      row of outer stalk cells, in the end walls connecting the outer stalk cells, and
      the end walls connecting the inner stalk cells: these strategically located
      plasmodesmata presumably permit the electrotonic spread of receptor potentials
      and action potentials between cells. 

PMID- 24458986
TI  - Polyphenols in lahpet-so and two new catechin metabolites produced by anaerobic
      microbial fermentation of green tea.
AB  - The phenolic constituents of lahpet-so, a traditional postfermented tea of
      Myanmar produced under anaerobic conditions, were examined. The major polyphenols
      were identified to be pyrogallol and 4'-hydroxyphenyl-3-(2'',4'',6''
      trihydroxyphenyl)-propan-2-ol, 3',4'-dihydroxyphenyl-3-(2'',4'',6''
      trihydroxyphenyl)-propan-2-ol, and 3',4',5'-trihydroxyphenyl-3-(2'',4'',6''
      trihydroxyphenyl)-propan-2-ol. The hydroxydiphenylpropan-2-ols were identical to
      the initial metabolites produced from green tea catechins by mammalian intestinal
      bacteria. In addition, an anaerobic mixed-fermentation experiment using lahpet-so
      and Japanese commercial green tea afforded two new catechin degradation products
      together with known compound bruguierol B and the above-mentioned catechin
      metabolites. Based on spectroscopic evidence, the structures of the new compounds
      were concluded to be 4-(2,5-dihydroxyhexyl)benzene-1,2-diol and (5S,8R)-6,7,8,9
      tetrahydro-5-methyl-5.8-epoxy-5H-benzocycloheptene-2,3,4-triol. Interestingly,
      the production mechanism was deduced to be the inverse of the biosynthesis of the
      flavan-3-ol A ring. 

PMID- 24458988
TI  - Phytochrome effect on free amino acid metabolism of higher plants.
AB  - Activated phytochrome lowers the free amino acid pools of all plants investigated
      by about 15%. The action of red light is preferentially directed to Asp, Glu and
      Phe. Exogenously supplied Leu-U-(14)C is incorporated more quickly into protein
      of red-light-treated samples compared with dark controls. In contrast, red light
      decreases the amount of Asp-U-(14)C incorporated into protein, but increases the
      amount of (14)CO2 respired after feeding with Asp-U-(14)C. Red light has no
      effect on the amount of (14)CO2 respired after feeding with Leu-U-(14)C. Red
      light-mediated stimulation of incorporation of Leu-U-(14)C into protein occurred
      within 15 min, well before the red-light-mediated increase in (14)CO2 production
      following feeding with Asp-U-(14)C could be detected. 

PMID- 24458989
TI  - The influence of inorganic nitrogen supply on amination and related reactions in
      the blue-green alga, Anabaena cylindrica Lemm.
AB  - The occurrence of glutamate (GDH), alanine (AlaDH), and aspartate (AspDH)
      dehydrogenases, glutamine synthetase, ornithine transcarbamylase, and several
      aminotransferases was demonstrated in preparations of vegetative cells of
      Anabaena cylindrica cultured on an inorganic medium supplied with gaseous
      nitrogen or additionally supplemented with either ammonia, nitrite, or nitrate.
      GDH was mainly NADPH-linked in extracts of algae grown in the presence of
      atmospheric nitrogen and also ammonia, whilst nitrite and nitrate cultures
      predominantly showed NADH-linked activity. High activities of both AlaDH and
      AspDH were recorded in nitrogen-fixing algae; both amino acid dehydrogenases were
      NADH-specific. GDH in nitrogen-fixing cultures was the only enzyme of reductive
      amination found in appreciable amount in the lamellar fraction. Glutamine
      synthetase was most active in alga cultured on nitrogen, whilst greatest
      ornithine transcarbamylase activity was observed in ammonia-grown filaments.
      Aspartate-glutamate exceeded aspartate-alanine aminotransferase activity under
      all culture conditions and both were mainly localised in the supernatant
      fraction.Changes in activity of the amino acid dehydrogenases were attributed to
      cofactor competition with reductive processes involved in nitrogen, nitrite, and
      nitrate assimilation. Glutamine synthetase was considered to be regulated by the
      availability of ATP, being least under nitrogen-fixing conditions. High ornithine
      transcarbamylase activity was interpreted to provide a means for removal of
      excessive levels of ammonia. 

PMID- 24458990
TI  - Biological specificity of the antheridogen. from Ceratopteris thalictroides (L.)
      Brongn.
AB  - The relationship of the antheridogen from Ceratopteris thalictroides (L.) Brongn.
      (Antheridogen C) to three other known antheridogens, gibberellic acid, and two
      natural antheridogens, one from Pteridium aquilinum (Antheridogen A) and one from
      Anemia phyllitidis (Antheridogen B), is investigated. It is shown that each is a
      biologically distinet entity, interspecific activity being absent. The
      antheridogen responses of two widely separated sources of C. thalictroides were
      also compared. The results indicate that both susceptibility and antheridogen
      production vary between the two sources. 

PMID- 24458991
TI  - Naturally-occurring growth regulators in leaf washings of Picea sitchensis
      (Bong.) Carr and Betula pendula Roth.
AB  - Leaf washings were collected during and immediately after periods of rainfall
      ('natural') from Picea sitchensis (Bong.) Carr and Betula pendula Roth., growing
      in the field. They contained acidic and non-acidic ethyl acetate-soluble growth
      regulating factors, including a gibberellin-like compound and an inhibitor
      resembling abscisic acid (ABA). Similar ranges of growth regulators were obtained
      when needles of Picea sitchensis were intermittently sprayed with a fine water
      mist ('artificial') in glasshouse conditions, greater amounts of an ABA-like
      compound occurring per unit volume of spray when intervals between spray
      applications were shortened. 

PMID- 24458993
TI  - The effect of auxin on the incorporation of [(3)H]thymidine into the DNA of pea
      epicotyls.
AB  - Preincubation of apical segments of etiolated peas (Pisum sativum L.) in indole-3
      acetic acid (IAA) results in an inhibition of the incorporation of [(3)H]
      thymidine ([(3)H]TdR) into DNA. Preincubation in IAA for 4 h led to an inhibition
      of [(3)H]TdR incorporation only at the highest concentration of IAA tested (10(
      4) M). A 20-h preincubation in various concentrations of IAA resulted in a
      bimodal dose response curve. High concentrations of IAA (10(-4) M) inhibited
      incorporation by ca. 50%, as did concentrations of about 10(-6)M, but 10(-5) M
      IAA did not inhibit this incorporation. The absorption of [(3)H]TdR was not
      affected by preincubation in IAA for either 4 or 20 h. When the apical segments
      were cut into two portions, the hook with the shoot apex, and the portion
      remaining below the apical hook, preincubation in IAA for 20 h gave different
      results for the upper and lower portions of the apical segments. In the lower
      portion, concentrations of about 5*10(-6) M gave a slight increase in [(3)H]TdR
      incorporation and 10(-4) M IAA inhibited DNA synthesis. In the upper portion, IAA
      pretreatment for 20 h resulted in a bimodal dose response curve which was very
      similar to that found initially for the entire apical segment. Thus the effect of
      pretreatment of apical segments with IAA depends upon the physiological status of
      the tissue. The rapidly expanding cells in the lower portion of the apical
      segments respond to IAA differently than the cells of the upper portion which are
      principally quiescent. 

PMID- 24458992
TI  - [Studies on the influence of abscisic acid and gibberellic acid on the activities
      of some enzymes of carbohydrate metabolism in leaves of Pennisetum typhoides
      seedlings].
AB  - Abscisic acid (ABA) and gibberellic acid (GA3), alone and in combination, were
      applied to Pennisetum typhoides seedlings and the effects on the activity of
      phosphorylase, amylase, invertase, hexose-phosphate-isomerase, sucrose-6
      phosphate-synthetase and sucrose-synthetase were studied. ABA-treatment inhibited
      the activity of amylase and invertase, but stimulated greatly that of
      phosphorylase, hexose-phosphate-isomerase, sucrose-6-phosphate-synthetase and
      sucrose-synthetase. GA3 alone, on the other hand, promoted the activity of
      invertase but had no significant influence on the other enzymes tested. Given in
      combination with ABA, GA3 completely overcomes the stimulative effect of ABA on
      sucrosesynthetase. 

PMID- 24458994
TI  - [Behavior of a mitochondrial population in the shoot apex of spinach].
AB  - In spinach (Spinacia oleracea) certain mitochondria of the sporogenic promeristem
      would appear to show lysosomal involvement. This occasional involvement occurs
      when the photoperiodic conditions do not favor flowering. The mitochondrial
      morphological changes indicate increase in the production of membrane. The acid
      phosphatase activity normally found in the neighbourhood of the dictyosomes is
      present. 

PMID- 24458995
TI  - The enzymatic incorporation of (32)P into ATP and other organic compounds by
      sieve-tube sap of Macrocystis integrifolia Bory.
AB  - The stipe of Macrocystis integrifolia Bory, when cut near its base, released
      sieve-tube sap at a rate of 1.55 to 2.1 ml h(-1). This sap contained a high
      amount of ATP. When the sap was incubated with (32)PO4 (3-) the radioactivity was
      rapidly incorporated into a number of organic compounds, of which ATP was the
      most heavily labeled. This incorporation was due to enzymatic activity present in
      the sieve tube sap. The physiological significance of these results in
      translocation of assimilates in the brown algae is discussed. 

PMID- 24458996
TI  - Association of melanocortin 4 receptor gene variation with satiation and gastric
      emptying in overweight and obese adults.
AB  - Melanocortin 4 receptor (MC4R) has a major role in energy homeostasis. The
      rs17782313 polymorphism, mapped 188 kb downstream from MC4R, has been associated
      with satiety, higher body mass index (BMI) and total calorie intake in adults. To
      assess the association of rs17782313 with gastric functions, satiation, or
      satiety, we studied 178 predominantly Caucasian overweight and obese people: 120
      females, 58 males; mean BMI 33.4 +/- 5.3 kg/m(2) (SD); age 37.7 +/- 11.2 years.
      Quantitative traits assessed were gastric emptying (GE) of solids and liquids;
      fasting and postprandial gastric volume; satiation by maximum tolerated volume
      and 4 symptoms by 100-mm visual analog scales (VAS); and satiety by ad libitum
      buffet meal. Associations of genotype and quantitative traits were assessed by
      analysis of covariance (using gender and BMI as covariates), based on a dominant
      [TC (n = 72) - CC (n = 12) vs. TT (n = 94)] genetic model. rs17782313(C) was
      associated with postprandial satiation symptoms (median Delta total VAS 26.5 mm,
      p = 0.036), reduced proportion of solid GE at 2 h (median Delta 6.7 %, p = 0.008)
      and 4 h (median Delta 3.2 %, p = 0.006), and longer t 1/2 (median Delta 6 min, p
      = 0.034). Associations of rs17782313 with obesity may be explained by reduced
      satiation and GE. The role of MC4R mechanisms in satiation and gastric function
      deserves further study. 

PMID- 24458997
TI  - Mispairs with Watson-Crick base-pair geometry observed in ternary complexes of an
      RB69 DNA polymerase variant.
AB  - Recent structures of DNA polymerase complexes with dGMPCPP/dT and dCTP/dA
      mispairs at the insertion site have shown that they adopt Watson-Crick geometry
      in the presence of Mn(2+) indicating that the tautomeric or ionization state of
      the base has changed. To see whether the tautomeric or ionization state of base
      pair could be affected by its microenvironment, we determined 10 structures of an
      RB69 DNA polymerase quadruple mutant with dG/dT or dT/dG mispairs at position n-1
      to n-5 of the Primer/Template duplex. Different shapes of the mispairs, including
      Watson-Crick geometry, have been observed, strongly suggesting that the local
      environment of base-pairs plays an important role in their tautomeric or
      ionization states. 

PMID- 24458998
TI  - Ameliorative effect of polyphenols from Padina boergesenii against ferric
      nitrilotriacetate induced renal oxidative damage: With inhibition of oxidative
      hemolysis and in vitro free radicals.
AB  - The aim of this study was to evaluate the antioxidant activities of diethyl ether
      (DEE) and methanol (M) extracts from brown alga Padina boergesenii using in vitro
      and in vivo antioxidant assay, which may help to relate the antioxidant
      properties with the possible outline of its ameliorative effect. M extract showed
      higher radical scavenging activity through ferric reducing antioxidant power
      139.11 umol tannic acid equivalent/g; DPPH 71.32 +/- 0.56%; deoxyribose radical
      88.31 +/- 0.47%, and total antioxidant activity 0.47 +/- 0.02 mg ascorbic acid
      equivalents/g. Oxidative red blood cell (RBC) hemolysis inhibition rate was
      significantly higher in M extract (150 mg/kg body weight) in reference to total
      phenolic content (r = 0.935). Rats administered with DEE and M extracts (150
      mg/kg body weight) for seven days before the administration of ferric
      nitrilotriacetate (9 mg of Fe/mg/kg bodyweight). Rats pretreated with extracts
      significantly changed the level of renal microsomal lipid peroxidation,
      glutathione, and antioxidant enzymes in post-mitochondrial supernatant (P <
      0.05). Ameliorative effect of extracts against renal oxidative damage was evident
      in rat kidney through changes in necrotic and epithelial cells. HPTLC technique
      has identified the presence of rutin with reference to retardation factor (Rf )
      in both the extracts. These findings support the source of polyphenols (rutin)
      from P. boergesenii had potent antioxidant activity; further work on isolation of
      bioactive compounds can be channeled to develop as a natural antioxidant.

PMID- 24458999
TI  - Magnesium biomaterials for orthopedic application: a review from a biological
      perspective.
AB  - Magnesium (Mg) has a long history of investigation as a degradable biomaterial.
      Physicians first began using Mg for biomedical applications in the late 19th
      century. Experimentation continued with varying levels of success until the mid
      20th century when interest in the metal waned. In recent years the field of Mg
      based biomaterials has once again become popular, likely due to advancements in
      technology allowing improved control of corrosion. Although this has led to
      success in vascular applications, continued difficulties in predicting and
      controlling the corrosion rate of Mg in an intraosseous environment has impeded
      the development of Mg-based biomaterials for orthopedic applications. In this
      review, an initial summary of the basic properties and the physiological role of
      Mg are followed by a discussion of the physical characteristics of the metal
      which lend it to use as a degradable biomaterial. A description of the historical
      and modern applications for Mg in the medical field is followed by a discussion
      of the methods used to control and assess Mg corrosion, with an emphasis on
      alloying. The second part of this review concentrates on the methods used to
      assess the corrosion and biocompatibility of Mg-based orthopedic biomaterials.
      This review provides a summary of Mg as a biomaterial from a biological
      perspective.

PMID- 24459000
TI  - Skin-to-skin care for procedural pain in neonates.
AB  - BACKGROUND: Skin-to-skin care (SSC), otherwise known as Kangaroo Care (KC) due to
      its similarity with marsupial behaviour of ventral maternal-infant contact, is
      one non-pharmacological intervention for pain control in infants. OBJECTIVES: The
      primary objectives were to determine the effect of SSC alone on pain from medical
      or nursing procedures in neonates undergoing painful procedures compared to no
      intervention, sucrose or other analgesics, or additions to simple SSC such as
      rocking; and the effects of the amount of SSC (duration in minutes) and the
      method of administration (who provided the SSC, positioning of caregiver and
      neonate pair).The secondary objectives were to determine the incidence of
      untoward effects of SSC and to compare the SSC effect in different postmenstrual
      age subgroups of infants. SEARCH METHODS: The standard methods of the Cochrane
      Neonatal Collaborative Review Group were used. Databases searched in August 2011:
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane
      Library); Evidence-Based Medicine Reviews; MEDLINE (1950 onwards); PubMed (1975
      onwards); EMBASE (1974 onwards); CINAHL (1982 onwards); Web of Science (1980
      onwards); LILACS database (1982 onwards); SCIELO database (1982 onwards);
      PsycInfo (1980 onwards); AMED (1985 onwards); Dissertation-Abstracts
      International (1980 onwards). Searches were conducted throughout September 2012.
      SELECTION CRITERIA: Studies with randomisation or quasi-randomisation, double or
      single-blinded, involving term infants (> 37 completed weeks postmenstrual age
      (PMA)) to a maximum of 44 weeks PMA and preterm infants (< 37 completed weeks
      PMA) receiving SSC for painful procedures conducted by doctors, nurses, or other
      healthcare professionals. DATA COLLECTION AND ANALYSIS: The main outcome measures
      were physiological or behavioural pain indicators and composite pain scores. A
      weighted mean difference (WMD) with 95% confidence interval (CI) using a fixed
      effect model was reported for continuous outcome measures. We included variations
      on type of tissue-damaging procedure, provider of care, and duration of SSC. MAIN
      RESULTS: Nineteen studies (n = 1594 infants) were included. Fifteen studies (n =
      744) used heel lance as the painful procedure, one study combined venepuncture
      and heel stick (n = 50), two used intramuscular injection, and one used
      'vaccination' (n = 80). The studies that were included were generally strong and
      free from bias.Eleven studies (n = 1363) compared SSC alone to a no-treatment
      control. Although 11 studies measured heart rate during painful procedures, data
      from only four studies (n = 121) could be combined to give a mean difference (MD)
      of 0.35 beats per minute (95% CI -6.01 to 6.71). Three other studies that were
      not included in meta-analyses also reported no difference in heart rate after the
      painful procedure. Two studies reported heart rate variability outcomes and found
      no significant differences. Five studies used the Premature Infant Pain Profile
      (PIPP) as a primary outcome, which favoured SCC at 30 seconds (n = 268) (MD 
      3.21, 95% CI -3.94 to -2.48), 60 seconds (n = 164) (MD -1.85, 95% CI -3.03 to 
      0.68), and 90 seconds (n = 163) (MD -1.34, 95% CI -2.56 to -0.13), but at 120
      seconds (n = 157) there was no difference. No studies provided findings on return
      of heart rate to baseline level, oxygen saturation, cortisol levels, duration of
      crying, and facial actions that could be combined for analysis.Eight studies
      compared SSC to another intervention with or without a no-treatment control. Two
      cross-over studies (n = 80) compared mother versus other provider on PIPP scores
      at 30, 60, 90, and 120 seconds with no significant difference. When SSC was
      compared to other interventions, there were not enough similar studies to pool
      results in an analysis. One study compared SSC with and without dextrose and
      found that the combination was most effective and that SSC alone was more
      effective than dextrose alone. Similarly, in another study SSC was more effective
      than oral glucose for heart rate but not oxygen saturation. SSC either in
      combination with breastfeeding or alone was favoured over a no-treatment control,
      but was not different to breastfeeding. There were not enough participants with
      similar outcomes and painful procedures to compare age groups or duration of SSC.
      No adverse events were reported in any of the studies. AUTHORS' CONCLUSIONS: SSC
      appears to be effective, as measured by composite pain indicators and including
      both physiological and behavioural indicators, and safe for a single painful
      procedure such as a heel lance. Purely behavioural indicators tended to favour
      SSC but there remains questionable bias regarding behavioural indicators.
      Physiological indicators were typically not different between conditions. Only
      two studies compared mother providers to others, with non-significant results.
      There was more heterogeneity in the studies with behavioural or composite
      outcomes. There is a need for replication studies that use similar, clearly
      defined outcomes. New studies examining optimal duration of SSC, gestational age
      groups, repeated use, and long-term effects of SSC are needed.

PMID- 24459001
TI  - [Quality of vocational education in speech therapy - development and
      implementation of a quality assurance programme].
AB  - The provision of high-quality health-services is only possible if it is based on
      vocational education of corresponding quality. To promote the quality of
      vocational education in speech therapy, a quality assurance programme was
      developed in a scientifically supervised multi-step process. The main goals of
      the quality assurance programme include: (i) external review of the quality of
      education by means of well-defined criteria, (ii) certification of schools that
      meet the requirements, and (iii) provision of feedback to schools about their
      results. A total of 208 quality indicators cover the essential aspects of
      vocational education in speech therapy, and apply to the structural, process and
      outcome quality. These indicators are based on a literature survey as well as on
      expert opinion, and are calibrated by data. The data are collected by using
      questionnaires (school management, teachers in speech therapy, students,
      consecutive patient sample) and are validated by specific document analyses and
      telephone audits. Each school receives an individual quality report of its
      achieved results benchmarked to other schools. Since the initial implementation
      in 2008, a total of 50 schools participated in the quality assurance programme
      and 41 achieved certification. Therefore, the defined set of quality criteria has
      been disseminated and utilized by about half of all German schools for vocational
      education in speech therapy. The evaluation of the data on quality collected
      across all schools highlights the strengths and weaknesses of vocational
      education as well as the demands for quality improvement. 

PMID- 24459002
TI  - Modification of extended open frameworks with fluorescent tags for sensing
      explosives: competition between size selectivity and electron deficiency.
AB  - Three new electron-rich metal-organic frameworks (MOF-1-MOF-3) have been
      synthesized by employing ligands bearing aromatic tags. The key role of the
      chosen aromatic tags is to enhance the pi-electron density of the luminescent
      MOFs. Single-crystal X-ray structures have revealed that these MOFs form three
      dimensional porous networks with the aromatic tags projecting inwardly into the
      pores. These highly luminescent electron-rich MOFs have been successfully
      utilized for the detection of explosive nitroaromatic compounds (NACs) on the
      basis of fluorescence quenching. Although all of the prepared MOFs can serve as
      sensors for NACs, MOF-1 and MOF-2 exhibit superior sensitivity towards 4
      nitrotoluene (4-NT) and 2,4-dinitrotoluene (DNT) compared to 2,4,6
      trinitrotoluene (TNT) and 1,3,5-trinitrobenzene (TNB). MOF-3, on the other hand,
      shows an order of sensitivity in accordance with the electron deficiencies of the
      substrates. To understand such anomalous behavior, we have thoroughly analyzed
      both the steady-state and time-resolved fluorescence quenching associated with
      these interactions. Determination of static Stern-Volmer constants (KS) as well
      as collisional constants (KC) has revealed that MOF-1 and MOF-2 have higher KS
      values with 4-NT than with TNT, whereas for MOF-3 the reverse order is observed.
      This apparently anomalous phenomenon was well corroborated by theoretical
      calculations. Moreover, recyclability and sensitivity studies have revealed that
      these MOFs can be reused several times and that their sensitivities towards TNT
      solution are at the parts per billion (ppb) level.

PMID- 24459003
TI  - Simultaneous electrochemical determination of L-cysteine and L-cysteine disulfide
      at carbon ionic liquid electrode.
AB  - A linear sweep voltammetric method is used for direct simultaneous determination
      of L-cysteine and L-cysteine disulfide (cystine) based on carbon ionic liquid
      electrode. With carbon ionic liquid electrode as a high performance electrode,
      two oxidation peaks for L-cysteine (0.62 V) and L-cysteine disulfide (1.3 V) were
      observed with a significant separation of about 680 mV (vs. Ag/AgCl) in phosphate
      buffer solution (pH 6.0). The linear ranges were obtained as 1.0-450 and 5.0-700
      MUM and detection limits were estimated to be 0.298 and 4.258 MUM for L-cysteine
      and L-cysteine disulfide, respectively. This composite electrode was applied for
      simultaneous determination of L-cysteine and L-cysteine disulfide in two real
      samples, artificial urine and nutrient broth. Satisfactory results were obtained
      which clearly indicate the applicability of the proposed electrode for
      simultaneous determination of these compounds in complex matrices. 

PMID- 24459004
TI  - Improvements to polar 2-D electrophoresis for proteomic applications.
AB  - Recently, we reported a new way of performing 2-DE, called P-dimensional
      electrophoresis (2-PE). In this approach, the second dimension is achieved in a
      radial gel which can accommodate up to six 7 cm long IPG strips simultaneously,
      improving reproducibility and throughput power in respect to 2-DE. Nevertheless,
      2-PE was up to now limited to the use of only short strips because of technical
      difficulties. Here, we describe how to load longer strips (e.g., 18-24 cm) on 2
      PE and report some representative images for a qualitative assessment. 

PMID- 24459005
TI  - Invasive fungal sinusitis in a healthy athlete due to long-term anabolic steroid
      use.
AB  - Invasive fungal rhinosinusitis is a potentially fatal infection that affects
      immunocompromised patients. Prognosis is generally poor despite aggressive
      medical and surgical treatments. We present the first reported case of invasive
      fungal sinusitis in a healthy 18-year-old male athlete who was taking anabolic
      androgenic steroids (AAS). The effects of excessive AAS use on the immune system
      are not fully understood, but there may be consequences at supraphysiological
      concentrations. This case demonstrates potential immunomodulatory effects of
      anabolic steroids and highlights a previously unknown cause of invasive fungal
      sinusitis.

PMID- 24459006
TI  - Fluconazole associated agranulocytosis and thrombocytopenia.
AB  - CASE: We describe a second case of fluconazole associated agranulocytosis with
      thrombocytopenia and recovery upon discontinuation of therapy. The patient began
      to have changes in white blood cells and platelets within 48 h of administration
      of fluconazole and began to recover with 48 h of discontinuation. This case
      highlights that drug-induced blood dyscrasias can occur unexpectedly as a result
      of treatment with a commonly used drug thought to be "safe". CONCLUSION:
      According to Naranjo's algorithm the likelihood that our patient's
      agranulocytosis and thrombocytopenia occurred as a result of therapy with
      fluconazole is probable, with a total of six points. We feel that the weight of
      the overall evidence of this evidence is strong. In particular the temporal
      relationship of bone marrow suppression to the initiation of fluconazole and the
      abatement of symptoms that rapidly reversed immediately following
      discontinuation.

PMID- 24459007
TI  - Acoustically active liposome-nanobubble complexes for enhanced ultrasonic imaging
      and ultrasound-triggered drug delivery.
AB  - Ultrasound is well known as a safe, reliable imaging modality. A historical
      limitation of ultrasound, however, was its inability to resolve structures at
      length scales less than nominally 20 um, which meant that classical ultrasound
      could not be used in applications such as echocardiography and angiogenesis where
      one requires the ability to image small blood vessels. The advent of ultrasound
      contrast agents, or microbubbles, removed this limitation and ushered in a new
      wave of enhanced ultrasound applications. In recent years, the microbubbles have
      been designed to achieve yet another application, namely ultrasound-triggered
      drug delivery. Ultrasound contrast agents are thus tantamount to 'theranostic'
      vehicles, meaning they can do both therapy (drug delivery) and imaging
      (diagnostics). The use of ultrasound contrast agents as drug delivery vehicles,
      however, is perhaps less than ideal when compared to traditional drug delivery
      vehicles (e.g., polymeric microcapsules and liposomes) which have greater drug
      carrying capacities. The drawback of the traditional drug delivery vehicles is
      that they are not naturally acoustically active and cannot be used for imaging.
      The notion of a theranostic vehicle is sufficiently intriguing that many attempts
      have been made in recent years to achieve a vehicle that combines the
      echogenicity of microbubbles with the drug carrying capacity of liposomes. The
      attempts can be classified into three categories, namely entrapping, tethering,
      and nesting. Of these, nesting is the newest-and perhaps the most promising.

PMID- 24459008
TI  - Optimization of effects-assessment of greenside darter (Etheostoma blennioides)
      exposed to tertiary treated municipal wastewater based on seasonal changes of
      reproductive endpoints.
AB  - The present study describes the seasonal changes in reproductive endpoints of the
      greenside darter (Etheostoma blennioides) and its implications for environmental
      monitoring. Fish collections conducted at the appropriate time for the site
      specific sentinel fish species can provide a wide variety of population-level
      information including recruitment, reproduction, and energy storage. The
      objectives of the present study were to: 1) characterize seasonal changes in
      reproductive endpoints of the greenside darter (both sexes) to determine the
      appropriate period for monitoring of this sentinel species; and 2) evaluate the
      effect of exposure of this sentinel species to tertiary treated municipal
      effluent at the selected monitoring period. Based on the selected parameters
      (gonadosomatic index [GSI], liver somatic index [LSI], condition factor, and in
      vitro gonadal steroid production [testosterone (T) in both sexes; estradiol (E2)
      in females; and 11-ketotestosterone (11KT) in males]), the present study provides
      evidence for the value of collecting darters during recrudescence (late
      fall/early winter) to ensure temporal stability, minimum variability, and stable
      steroid production capacity. Darters exposed to tertiary treated municipal
      effluent tended to be larger and heavier relative to reference fish but did not
      demonstrate any consistent responses in terms of condition or relative liver
      size. No effect on gonadal development was observed, even though these tertiary
      effluent-exposed fish demonstrated a significant reduction in the ability to
      produce hormones. The present study suggests that although fish exposed to
      tertiary treated effluent demonstrate no population-level effects, they are still
      responding at a physiological level. Documentation of the reproductive cycle of
      sentinel species allows for selection of the most appropriate sampling period to
      reduce variability and greatly enhances the reliability and interpretation of
      biological responses.

PMID- 24459009
TI  - Protection from radiation-induced apoptosis by the radioprotector amifostine (WR
      2721) is radiation dose dependent.
AB  - The radioprotective agent amifostine is a free radical scavenger that can protect
      cells from the damaging effects of ionising radiation when administered prior to
      radiation exposure. However, amifostine has also been shown to protect cells from
      chromosomal mutations when administered after radiation exposure. As apoptosis is
      a common mechanism by which cells with mutations are removed from the cell
      population, we investigated whether amifostine stimulates apoptosis when
      administered after radiation exposure. We chose to study a relatively low dose
      which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and
      a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400
      mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or
      6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow.
      We observed a significant increase in radiation-induced apoptosis in the spleen
      of mice when amifostine was administered before or after 0.25 Gy X-rays. In
      contrast, when a high dose of radiation was used (6 Gy), amifostine caused a
      reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone
      marrow similar to previously published studies. This is the first study to
      investigate the effect of amifostine on radiation-induced apoptosis at a
      relatively low radiation dose and the first to demonstrate that while amifostine
      can reduce apoptosis from high doses of radiation, it does not mediate the same
      effect in response to low-dose exposures. These results suggest that there may be
      a dose threshold at which amifostine protects from radiation-induced apoptosis
      and highlight the importance of examining a range of radiation doses and
      timepoints.

PMID- 24459010
TI  - A novel phenotype associated with cutis laxa, abnormal fat distribution,
      cardiomyopathy and cataract.
AB  - Cutis laxa (CL) is a connective tissue disorder, characterized by loose,
      inelastic, sagging skin. Both acquired and inherited (dominant, recessive, and X
      linked) forms exist. Here, we describe a new phenotype, which overlaps with other
      known CL syndromes. Our patient has a unique combination of features in
      association with sagging, inelastic, wrinkled skin, including cataract, severe
      cardiomyopathy, abnormal fat distribution, improvement of skin-wrinkling with
      age, and white matter abnormalities but no significant histologic collagen or
      elastin abnormalities. Mutation analysis of known CL genes was negative. We
      suggest that our patient has a novel syndrome, with the main features of CL,
      intellectual disability, abnormal fat distribution, cardiomyopathy, and cataract.

PMID- 24459011
TI  - A quarter of waiting time records are wrong, finds English watchdog.

PMID- 24459012
TI  - Somatic CTNNB1 mutation in hepatoblastoma from a patient with Simpson-Golabi
      Behmel syndrome and germline GPC3 mutation.
AB  - Simpson-Golabi-Behmel syndrome is a rare overgrowth syndrome caused by the GPC3
      mutation at Xq26 and is clinically characterized by multiple congenital
      abnormalities, intellectual disability, pre/postnatal overgrowth, distinctive
      craniofacial features, macrocephaly, and organomegaly. Although this syndrome is
      known to be associated with a risk for embryonal tumors, similar to other
      overgrowth syndromes, the pathogenetic basis of this mode of tumorigenesis
      remains largely unknown. Here, we report a boy with Simpson-Golabi-Behmel
      syndrome who had a germline loss-of function mutation in GPC3. At 9 months of
      age, he developed hepatoblastoma. A comparison of exome analysis results for the
      germline genome and for the tumor genome revealed a somatic mutation, p.Ile35Ser,
      within the degradation targeting box of beta-catenin. The same somatic mutation
      in CTNNB1 has been repeatedly reported in hepatoblastoma and other cancers. This
      finding suggested that the CTNNB1 mutation in the tumor tissue represents a
      driver mutation and that both the GPC3 and the CTNNB1 mutations contributed to
      tumorigenesis in a clearly defined sequential manner in the propositus. The
      current observation of a somatic CTNNB1 mutation in a hepatoblastoma from a
      patient with a germline GPC3 mutation supports the notion that the mutation in
      GPC3 may influence one of the initial steps in tumorigenesis and the progression
      to hepatoblastoma.

PMID- 24459013
TI  - Inactivation of mTor arrests bovine oocytes in the metaphase-I stage, despite
      reversible inhibition of 4E-BP1 phosphorylation.
AB  - The mammalian target of rapamycin (mTor), a Ser/Thr protein kinase, is implicated
      in the phosphorylation-triggered inactivation of translation repressors, the so
      called eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs).
      Previous observations in porcine and bovine oocytes revealed an increasing
      phosphorylation of 4E-BP1 during meiotic maturation. This factor is
      hypophosphorylated in the germinal-vesicle (GV) stage and its phosphorylation
      peaks in the metaphase II (M II) stage. In the present approach we intended to
      block 4E-BP1 phosphorylation specifically to impair initiation of translation and
      elucidate effects on resumption of meiosis. Torin2, which acts as an active-site
      mTor inhibitor, reduces 4E-BP1 phosphorylation without any effect on eIF4E and
      arrests up to 60% of the oocytes in the M I stage. Effects of Torin2 treatment,
      analyzed by site-specific substrate phosphorylation, were also observed at
      protein kinase B (Akt or PKB), and cyclin dependent kinases (CDKs). Only minor
      side effects were found at protein kinase A, C (PKA, PKC), ATM/ATR (Ataxia
      telangiectasia mutated/AT and Rad3-related protein), and the mitogen activated
      protein kinases (MAPK) ERK1,2. The inhibition of 4E-BP1 phosphorylation by Torin2
      is reversible when cultivating oocytes for additional 24 hr in Torin2-free
      medium. Even so, oocytes persist in the M I stage. This may indicate the
      necessity of spatiotemporally regulated translation during meiosis, which cannot
      be restored later. In conclusion, Torin2 enables an effective and specific
      inhibition of 4E-BP1 phosphorylation, which may be valuable to investigate
      maturation specific protein synthesis in more detail.

PMID- 24459014
TI  - Behavioral health aides in rural Alaska: their experience in caring for Alaska
      Native cancer survivors.
AB  - The Alaska Native Tribal Health Consortium conducted a statewide survey of rural
      community behavioral health aides (BHAs) within the tribal health system to
      assess their need for psychological and emotional support training for their work
      with cancer survivors. An electronic survey was distributed to all 114 rural BHAs
      in Alaska. They were asked about cancer survivors living in their community,
      whether they had been called to provide counseling to those survivors and about
      their comfort level in addressing cancer-related emotional issues and concerns
      experience by the patients and their families. Sixty-one (54 %) BHAs responded,
      62 % knew of cancer survivors in their community, and 88 % of whom agreed that it
      is their job to provide support to those cancer survivors. Of the 47 % of BHAs
      who had provided counseling to cancer survivors, 63 % noted a lack of adequate
      training about how to provide that counseling. Dealing with "emotional concerns"
      was reported as the most difficult issue. Almost all (98 %) reported that they
      would likely participate in training to improve counseling skills. Most BHAs in
      rural Alaska know of a cancer survivor in their community and may be called on to
      provide mental health services, but few report adequate training in how to
      provide these services. Given the remote locations in which many BHAs work and
      the lack of local resources to guide them, more education is needed about how to
      support cancer survivors. This study provides information to help guide
      development of content of that education. 

PMID- 24459015
TI  - Effects of tetrabrombisphenol A on DNA integrity, oxidative stress, and sterlet
      (Acipenser ruthenus) spermatozoa quality variables.
AB  - The sperm of sterlet (Acispenser ruthenus) was used to investigate the effect of
      the xenobiotic tetrabrombisphenol A (TBBPA) on sperm quality variables (ATP
      content, spermatozoa motility, and velocity), DNA integrity, and oxidative stress
      indices. Sperm was diluted to obtain a spermatozoa density of 5 * 10(8) cells/mL
      and exposed for 2 h to final concentrations of TBBPA (0.5, 1.75, 2.5, 5, and 10
      MUg/L). The oxidative stress indices, including lipid peroxidation, carbonyl
      derivatives of proteins, and antioxidant activity were significantly higher with
      increased concentrations of TBBPA. There was significantly less intracellular ATP
      in sperm samples at TBBPA concentrations of 2.5 MUg/L and above. Spermatozoa
      velocity and percent motile sperm were significantly lower at each sampling time
      post-activation compared to controls. DNA damage expressed as percent DNA in Tail
      and Olive Tail moment was significantly higher with exposures >=2.5 MUg/L TBBPA.
      The results demonstrated that TBBPA and other xenobiotics can induce reactive
      oxygen species stress in fish spermatozoa, which could impair the sperm quality,
      DNA integrity, ATP content, and the antioxidant defense system. This study
      confirmed that fish spermatozoa can be used in in vitro assays for monitoring
      residual pollution in aquatic environments.

PMID- 24459016
TI  - Acupuncture and related interventions for smoking cessation.
AB  - BACKGROUND: Acupuncture and related techniques are promoted as a treatment for
      smoking cessation in the belief that they may reduce nicotine withdrawal
      symptoms. OBJECTIVES: The objectives of this review are to determine the
      effectiveness of acupuncture and the related interventions of acupressure, laser
      therapy and electrostimulation in smoking cessation, in comparison with no
      intervention, sham treatment, or other interventions. SEARCH METHODS: We searched
      the Cochrane Tobacco Addiction Group Specialized Register (which includes trials
      of smoking cessation interventions identified from the Cochrane Central Register
      of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO) and AMED in
      October 2013. We also searched four Chinese databases in September 2013: Sino
      Med, China National Knowledge Infrastructure, Wanfang Data and VIP. SELECTION
      CRITERIA: Randomized trials comparing a form of acupuncture, acupressure, laser
      therapy or electrostimulation with either no intervention, sham treatment or
      another intervention for smoking cessation. DATA COLLECTION AND ANALYSIS: We
      extracted data in duplicate on the type of smokers recruited, the nature of the
      intervention and control procedures, the outcome measures, method of
      randomization, and completeness of follow-up.We assessed abstinence from smoking
      at the earliest time-point (before six weeks) and at the last measurement point
      between six months and one year. We used the most rigorous definition of
      abstinence for each trial, and biochemically validated rates if available. Those
      lost to follow-up were counted as continuing smokers. Where appropriate, we
      performed meta-analysis pooling risk ratios using a fixed-effect model. MAIN
      RESULTS: We included 38 studies. Based on three studies, acupuncture was not
      shown to be more effective than a waiting list control for long-term abstinence,
      with wide confidence intervals and evidence of heterogeneity (n = 393, risk ratio
      [RR] 1.79, 95% confidence interval [CI] 0.98 to 3.28, I2 = 57%). Compared with
      sham acupuncture, the RR for the short-term effect of acupuncture was 1.22 (95%
      CI 1.08 to 1.38), and for the long-term effect was 1.10 (95% CI 0.86 to 1.40).
      The studies were not judged to be free from bias, and there was evidence of
      funnel plot asymmetry with larger studies showing smaller effects. The
      heterogeneity between studies was not explained by the technique used.
      Acupuncture was less effective than nicotine replacement therapy (NRT). There was
      no evidence that acupuncture is superior to psychological interventions in the
      short- or long-term. There is limited evidence that acupressure is superior to
      sham acupressure for short-term outcomes (3 trials, n = 325, RR 2.54, 95% CI 1.27
      to 5.08), but no trials reported long-term effects, The pooled estimate for
      studies testing an intervention that included continuous auricular stimulation
      suggested a short-term benefit compared to sham stimulation (14 trials, n = 1155,
      RR 1.69, 95% CI 1.32 to 2.16); subgroup analysis showed an effect for continuous
      acupressure (7 studies, n = 496, RR 2.73, 95% CI 1.78 to 4.18) but not
      acupuncture with indwelling needles (6 studies, n = 659, RR 1.24, 95% CI 0.91 to
      1.69). At longer follow-up the CIs did not exclude no effect (5 trials, n = 570,
      RR 1.47, 95% CI 0.79 to 2.74). The evidence from two trials using laser
      stimulation was inconsistent and could not be combined. The combined evidence on
      electrostimulation suggests it is not superior to sham electrostimulation (short
      term abstinence: 6 trials, n = 634, RR 1.13, 95% CI 0.87 to 1.46; long-term
      abstinence: 2 trials, n = 405, RR 0.87, 95% CI 0.61 to 1.23). AUTHORS'
      CONCLUSIONS: Although pooled estimates suggest possible short-term effects there
      is no consistent, bias-free evidence that acupuncture, acupressure, or laser
      therapy have a sustained benefit on smoking cessation for six months or more.
      However, lack of evidence and methodological problems mean that no firm
      conclusions can be drawn. Electrostimulation is not effective for smoking
      cessation. Well-designed research into acupuncture, acupressure and laser
      stimulation is justified since these are popular interventions and safe when
      correctly applied, though these interventions alone are likely to be less
      effective than evidence-based interventions.

PMID- 24459017
TI  - Nitrate reduction by photosynthetic purple bacteria.

PMID- 24459018
TI  - Comparison of chlorophyll a spectra in wild-type and mutant barley chloroplasts
      grown under day or intermittent light.
AB  - The absorption (640-710 nm) and fluorescence emission (670-710 nm) spectra (77 K)
      of wild-type and Chl b-less, mutant, barley chloroplasts grown under either day
      or intermittent light were analysed by a RESOL curve-fitting program. The usual
      four major forms of Chl a at 662, 670, 678 and 684 nm were evident in all of the
      absorption spectra and three major components at 686, 693 and 704 nm in the
      emission spectra. A broad Chl a component band at 651 nm most likely exists in
      all chlorophyll spectra in vivo. The results show that the mutant lacks not only
      Chl b, but also the Chl a molecules which are bound to the light-harvesting, Chl
      a/b, protein complex of normal plants. It also appears that the absorption
      spectrum of this antenna complex is not modified appreciably by its isolation
      from thylakoid membranes. 

PMID- 24459019
TI  - Responses of photosynthesis to irradiance and temperature in soybean, Glycine max
      (L.) Merr.
AB  - The response of photosynthesis to irradiance and temperature during growth was
      investigated in two soybean genotypes. Soybean is a species that can modify its
      structure and metabolism so as to adapt to differing light conditions; its
      responses to rapid changes in irradiance are characterized by their flexibility.
      However, the temperature during growth can change the response to irradiance:
      moreover, there may be a marked interaction with genotype.The response of
      photosynthesis to irradiance consists of changes in leaf thickness, which bring
      about variations in the mesophyll resistance to CO2 transfer. The increase in net
      photosynthesis per unit of leaf area is due to the increase in the amount of
      assimilating material beneath unit of area, as corroborated by the stability of
      the net photosynthesis per unit volume. Moreover, the response of photosynthesis
      to temperature is due to the mesophyll diffusion 'constant' which decreases with
      the growth temperature. 

PMID- 24459020
TI  - Changes in photosynthetic rates and growth following root treatments of tomato
      plants with phytohormones.
AB  - The effects of root applications of kinetin, gibberellic acid (GA3) and
      indoleacetic acid (IAA) on photosynthesis was measured using an open infrared CO2
      gas-exchange system. There was a 30-35% increase in the photosynthetic rates (mg
      CO2/dm(2)/hr) of attached leaves within 8 hr following root treatment with 0.47
      MUM kinetin. On a short-term basis (up to 2 days) 0.47 MUM kinetin was shown to
      have the optimal stimulatory effect on photosynthesis, relative growth rate (RGR)
      and total plant dry weight. If the roots were in contact with 0.47 MUM kinetin
      for longer than two days there was severe branching of the root system and growth
      was severely decreased. When plants were left in contact with the kinetin
      treatment for up to 7 days the optimal stimulatory concentration was considerably
      lower (0.0047 MUM) . Plants receiving a 4, 8, or 12 hr pulse with 0.47 MUM
      kinetin to the roots exhibited higher leaf photosynthetic rates than the control.
      Plants receiving an 8 or 12 hr pulse with 0.47 MUM kinetin maintained
      photosynthetic rates higher than the control for the duration of the experiment
      (8 days) while the 4 hr pulse remained higher than the control for only 5 days. A
      sharp decrease in the photosynthetic rate, RGR and total plant dry weight was
      observed two days following continual treatments with 0.47 MUM kinetin to the
      roots. At low light levels there was approximately a 100% increase in the
      photosynthetic rate two days following treatment with 0.47 MUM kinetin while at a
      saturating irradiance there was a 30 to 35% increase. Indoleacetic acid either
      showed no effect on the photosynthetic rate, RGR and total plant dry weight or an
      inhibitory effect was observed. Either GA3 or kinetin alone were shown to
      stimulate photosynthesis, RGR and total plant dry weight, however, when GA3 at a
      1.4 MUM concentration was applied in combination with kinetin at a 0.0047 MUM
      concentration to the roots of tomato plants there was no additive effect. In all
      cases kinetin dramatically reduced leaf resistance whereas GA3 had no effect.By
      supplying either GA3 or kinetin to the roots of tomato plants a highly
      reproducible stimulation in the photosynthetic rate, RGR and total plant dry
      weight can be achieved at physiologically relevant concentrations, whereas IAA
      appears to have an inhibitory effect. 

PMID- 24459021
TI  - Effect of growth conditions on carboxylating enzymes of Zea mays plants.
AB  - Phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31) and ribulose-1,5-bisphospate
      (RuBP) carboxylase (EC 4.1.1.39) activities in leaves of different maize hybrids
      grown under field conditions (high light intensity) and in a growth chamber (low
      light intensity) were determined. Light intensity and leaf age affected PEP
      carboxylase activity, whereas RuBP carboxylase was affected by leaf age only at
      low light intensity. PEP carboxylase/RuBP carboxylase activity ratio decreased
      according to light intensity and leaf age. Results demonstrate that Zea mays
      grown under field conditions is a typical C4 species in all leaves independently
      from their position on the stem, whereas it may be a C3 plant when it is grown in
      a growth chamber at low light intensity. 

PMID- 24459022
TI  - Photosynthetic characteristics of mesophyll eells isolated from sunflower
      (helianthus annuus L.) leaves.
AB  - Mesophyll cells were isolated from sunflower leaves by an enzymic procedure. The
      cell suspensions possessed high photosynthesis rates. The products of cell
      photosynthesis were similar to the products of leaf disc photosynthesis. The
      relatively high radioactivity incorporated into malate after (14)CO2 feeding
      suggests that PEP carboxylase might participate in CO2 fixation. Sunflower leaf
      extracts possessed a PEP carboxylase activity slightly higher than that of other
      C3 species. Inhibition of PEP carboxylase by maleate decreased cell
      photosynthesis by only 15% and the first products of cell photosynthesis were
      phosphorylated compounds. It is concluded that the high photosynthesis rates
      displayed by sunflower are not due to a parallel C4 pathway of photosynthesis but
      are rather dependent, at least in part, on the activity, or the amount, of RuBP
      carboxylase. 

PMID- 24459023
TI  - Paradigm shift from alkaline (earth) metals to early transition metals in
      fluoroorganometal chemistry: perfluoroalkyl titanocene(III) reagents prepared via
      not titanocene(II) but titanocene(III) species.
AB  - Perfluoroalkyl (RF) titanocene reagents [Cp2Ti(III)RF] synthesized via
      [Cp2Ti(III)Cl] rather than [Cp2Ti(II)] show new types of perfluoroalkylation
      reactions. The [Cp2Ti(III)RF] reagents exhibit a wide variety of reactivity with
      carbonyl compounds including esters and nitriles, and selectivities far higher
      than those reported for conventional RFLi and RFMgX reagents.

PMID- 24459031
TI  - Combined composite osteofasciocutaneous fibular free flap and radial head
      arthroplasty for reconstruction of the elbow joint.
AB  - Reconstruction of the radial head can be complicated in cases of wide resection,
      particularly in those cases including the proximal radial shaft. In such cases,
      radial head replacement may not be possible because of lack of adequate bone
      stock. Here, we report the use of a radial head prosthesis incorporated with a
      vascularized fibula for immediate anatomic restoration of the forearm and elbow.
      We present a case of a pathologic fracture non-union in the proximal radius in a
      57-year-old female with a history of multiple myeloma. Non-operative management
      of the fracture was unsuccessful after chemotherapy and radiation. The proximal
      radius and radial head were resected and reconstructed with vascularized fibula
      graft in conjunction with immediate radial head prosthesis. The osteotomy site
      healed at 6-weeks and follow-up at 1 year showed good functional outcome. We feel
      that the use of this construct has definite promise and may be considered for
      reconstruction following resection of the proximal radius.

PMID- 24459032
TI  - Birth weight and overweight or obesity risk in children under 3 years in China.
AB  - OBJECTIVE: To investigate the association between different levels of birth
      weight and the risk of overweight and obesity in children aged 3 years and under.
      METHODS: Between 2009 and 2011, health care records of 55,925 children had been
      collected, and body weight and length had been measured from birth to 3 years
      old. RESULTS: Prevalence of overweight/obesity (BMI >=85th percentiles and BMI
      >=95th percentiles, referring to WHO BMI standards) at 0.5, 1, 2, and 3 years of
      age are 34.7%/16.8%, 36.4%/17.7%, 26.6%/11.0%, 22.3%/9.3%, respectively. There
      was a positive association between birth weight and childhood overweight or
      obesity from 6 months to 3 years of age. After adjustment for gestational age,
      maternal age, weight gain during pregnancy, maternal history of diabetes,
      mother's and father's education, occupation, and health status, family income,
      feeding modalities, and sex, the odds ratios (ORs) of overweight or obesity were
      significantly higher among children whose birth weights were 3,000-3,499 g (1.35
      1.53 folds), 3,500-3,999 g (2.09-2.37 folds), 4,000-4,499 g (2.80-3.32 folds),
      and more than 4,500 g (3.54-4.90 folds), compared with the reference group (2,500
      2,999 g). CONCLUSIONS: Higher levels of birth weight were associated with an
      increased risk of overweight or obesity among Chinese children from 6 months to 3
      years of age.

PMID- 24459033
TI  - Inconsistency in circulating irisin levels: what is really happening?
AB  - The discovery of irisin as a novel and promising peptidic hormone for the
      treatment of obesity and diabetes has recently been reported. As a result, great
      hopes have been raised based on this finding, hypothesizing that irisin might
      provide additional benefits, not only for obesity and diabetes, but also for a
      wide range of pathological conditions requiring therapeutical and clinical
      attention. However, controversial results and conclusions on circulating irisin
      concentrations and correlations with other variables, including its role in
      metabolism, have recently been reported. Although laboratory assessment of irisin
      by ELISA is easily available and may provide interesting information for
      therapeutics and clinical practice, the heterogeneous and often discrepant
      results published so far, raise serious concerns about its measurement,
      indicating that it may still not be ready for use or whether irisin really
      exists. We highlight here some aspects on these discrepancies and contradictions,
      and put forward their implications. 

PMID- 24459034
TI  - Perspective on CFD studies of coronary artery disease lesions and hemodynamics: a
      review.
AB  - Coronary artery disease (CAD) is the most common cardiovascular disease. Early
      diagnosis of CAD's physiological significance is of utmost importance for guiding
      individualized risk-tailored treatment strategies. In this paper, we first review
      the state-of-the-art clinical diagnostic indices to quantify the severity of CAD
      and the associated invasive and noninvasive imaging technologies in order to
      quantify the anatomical parameters of diameter stenosis, area stenosis, and
      hemodynamic indices of coronary flow reserve and fractional flow reserve. With
      the development of computational technologies and CFD methods, tremendous
      progress has been made in applying image-based CFD simulation techniques to
      elucidate the effects of hemodynamics in vascular pathophysiology toward the
      initialization and progression of CAD. So then, we review the advancements of CFD
      technologies in patient-specific modeling, involving the development of geometry
      reconstruction, boundary conditions, and fluid-structure interaction. Next, we
      review the applications of CFD to stenotic sites, in order to compute their
      hemodynamic parameters and study the relationship between the hemodynamic
      conditions and the clinical indices, to thereby assess the amount of viable
      myocardium and candidacy for percutaneous coronary intervention. Finally, we
      review the strengths and limitations of current researches of applying CFD to CAD
      studies.

PMID- 24459035
TI  - Quantification of changes in language-related brain areas in autism spectrum
      disorders using large-scale network analysis.
AB  - PURPOSE: Diagnosis of autism spectrum disorders (ASD) is difficult, as symptoms
      vary greatly and are difficult to quantify objectively. Recent work has focused
      on the assessment of non-invasive diffusion tensor imaging-based biomarkers that
      reflect the microstructural characteristics of neuronal pathways in the brain.
      While tractography-based approaches typically analyze specific structures of
      interest, a graph-based large-scale network analysis of the connectome can yield
      comprehensive measures of larger-scale architectural patterns in the brain.
      Commonly applied global network indices, however, do not provide any specificity
      with respect to functional areas or anatomical structures. Aim of this work was
      to assess the concept of network centrality as a tool to perform locally specific
      analysis without disregarding the global network architecture and compare it to
      other popular network indices. METHODS: We create connectome networks from fiber
      tractographies and parcellations of the human brain and compute global network
      indices as well as local indices for Wernicke's Area, Broca's Area and the Motor
      Cortex. Our approach was evaluated on 18 children suffering from ASD and 18
      typically developed controls using magnetic resonance imaging-based cortical
      parcellations in combination with diffusion tensor imaging tractography. RESULTS:
      We show that the network centrality of Wernicke's area is significantly (p<0.001)
      reduced in ASD, while the motor cortex, which was used as a control region, did
      not show significant alterations. This could reflect the reduced capacity for
      comprehension of language in ASD. CONCLUSIONS: The betweenness centrality could
      potentially be an important metric in the development of future diagnostic tools
      in the clinical context of ASD diagnosis. Our results further demonstrate the
      applicability of large-scale network analysis tools in the domain of region
      specific analysis with a potential application in many different psychological
      disorders.

PMID- 24459036
TI  - De novo single exon deletion of AUTS2 in a patient with speech and language
      disorder: a review of disrupted AUTS2 and further evidence for its role in
      neurodevelopmental disorders.
AB  - The autism susceptibility candidate 2 (AUTS2) gene is suggested to play a
      critical role in early brain development, and its association with intellectual
      disability (ID), autism spectrum disorders, and other neurodevelopmental
      disorders (NDDs) has recently gained more attention. Genomic rearrangements and
      copy number variations (CNVs) involving AUTS2 have been implicated in a range of
      NDDs with or without congenital malformations and dysmorphic features. Here we
      report a 62 kb de novo deletion encompassing exon 6 of AUTS2 detected by
      chromosomal microarray analysis (CMA) in a 4.5 year-old female patient with
      severe speech and language disorder, history of tonic-clonic movements, and pes
      planus with eversion of the feet. This is one of the smallest de novo intragenic
      deletions of AUTS2 described in patients with NDDs. We reviewed previously
      reported small pathogenic CNVs (<300 kb) in 19 cases, and correlated their
      specific locations within AUTS2 as well as presence of enhancers, regulatory
      elements, and CpG islands with the clinical findings of these cases and our
      patient. Our report provides additional insight into the clinical spectrum of
      AUTS2 disruptions.

PMID- 24459037
TI  - The behavior of mastoidectomy cavities following modified radical mastoidectomy.
AB  - OBJECTIVES/HYPOTHESIS: An analysis of the frequency and intensity of
      postoperative aftercare required for modified radical mastoidectomy (MRM) and
      patterns of healing in the postoperative period. STUDY DESIGN: A retrospective
      review of all primary modified radical mastoidectomies carried out for
      cholesteatoma under the care of the senior author between the years of 2004 and
      2009 with minimum follow-up of 2 years. METHODS: The time and number of
      interventions required to achieve a stable and dry mastoid cavity were collected.
      Cross-sectional and longitudinal analysis of the behavior of the cavities was
      carried out. RESULTS: Overall, 73 cases (71 patients) were identified. Patients
      were followed up for a median of 45.7 months (interquartile range, 31.8-70.5).
      After initial debridement, most cavities settled rapidly, but this was not always
      predictable, with a large proportion requiring further clinical intervention
      after the cavity was stable, sometimes for prolonged periods of time. At the time
      of analysis, 73% had achieved a stable cavity, 17 (23%) still required attention
      (nine for wax removal and eight for debridement); two were lost to follow-up. No
      revision surgeries were required. At 6 months, 36% of cavities were settled, 42%
      at 1 year, 53% at 18 months, and 62% at 2 years. After two standard postoperative
      visits, a total of 632 visits were made by these patients. CONCLUSIONS: Following
      MRM, the majority of patients achieve a dry, self-cleaning mastoid cavity. This
      might require periods of intense care interspersed with periods of quiescence.
      These results allow the benefits of this procedure to be put in the context of
      the entire patient journey.

PMID- 24459038
TI  - Proposed regulations for research with biospecimens: responses from stakeholders
      at CTSA consortium institutions.
AB  - Secondary research with biospecimens acquired through clinical care and through
      research is often conducted without the informed consent of individuals from whom
      the specimens were acquired. While such uses are consistent with the current
      federal regulations, surveys of the general public suggest that many individuals
      would prefer more information and choice regarding research use of biospecimens.
      The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in
      2011 that proposed a number of potential changes in the regulations governing
      human subjects. These proposed regulations are particularly pertinent to
      institutions committed to research involving human subjects-including
      institutions in the NIH-funded Clinical and Translational Science Awards (CTSA)
      consortium. In this study, we reviewed public responses by CTSA-funded
      institutions and CTSA-affiliated organizations and groups regarding the proposed
      changes in the ANPRM with respect to research with biospecimens. Our results
      indicate that the majority of responses to the ANPRM from CTSA institutions were
      not supportive of the proposed changes. While many responses acknowledge a need
      to change current research practices regarding biospecimens, the proposed changes
      in the ANPRM received only limited support from this subgroup of academic
      research institutions.

PMID- 24459039
TI  - "I just have to stick with it and it'll work": experiences of adolescents and
      young adults with mental health concerns.
AB  - Mental health issues are common among adolescents and young adults but service
      utilization in this group is low. This study aimed to better understand the
      experiences of older adolescents and young adults who were experiencing symptoms
      of depression or anxiety, including the factors that affected their decision to
      seek treatment and their feelings about their experience of mental health issues.
      We conducted semi-structured interviews with 37 older adolescents and young
      adults. Participants tended to have a sophisticated understanding of the causes
      of mental disorders, but to have been unsure about whether their own experiences
      of depression or anxiety were the result of a mental disorder, or just "normal"
      experiences. They reported concerns about taking medication and about keeping
      information about their condition private. They also felt that it was important
      to them to be active participants in their own care. 

PMID- 24459040
TI  - Recovery from sleep disturbance precedes that of depression and anxiety following
      mild traumatic brain injury: a 6-week follow-up study.
AB  - OBJECTIVES: The detailed course of mental disorders at the acute and subacute
      stages of mild traumatic brain injury (mTBI), especially with regard to recovery
      from sleep disturbances, has not been well characterised. The aim of this study
      was to determine the course of depression, anxiety and sleep disturbance,
      following an mTBI. SETTING: We recruited patients with mTBI from three university
      hospitals in Taipei and healthy participants as control group for this study.
      PARTICIPANTS: 100 patients with mTBI (35 men) who were older than 20 years, with
      a Glasgow Coma Scale score of 13-15 and loss of consciousness for <30 min,
      completed the baseline and 6-week follow-up assessments. 137 controls (47 men)
      without TBI were recruited in the study. None of the participants had a history
      of cerebrovascular disease, mental retardation, previous TBI, epilepsy or severe
      systemic medical illness. PRIMARY OUTCOME MEASURES: The Beck Anxiety Inventory
      (BAI), the Beck Depression Inventory II (BDI), the Epworth Sleepiness Scale (ESS)
      and the Pittsburgh Sleep Quality Index (PSQI) were assessed for the patients with
      mTBI at baseline and 6 weeks after mTBI and for the controls. RESULTS: The ESS
      scores were not significantly different between the mTBI at baseline or at 6
      weeks after mTBI and controls. Although the BAI, BDI and PSQI scores of the mTBI
      group were significantly different than those of the control group at baseline,
      all had improved significantly 6 weeks later. However, only the PSQI score
      improved to a level that was not significantly different from that of the control
      group. CONCLUSIONS: Daytime sleepiness is not affected by mTBI. However, mTBI
      causes depression and anxiety and diminished sleep quality. Although all these
      conditions improve significantly within 6 weeks post-mTBI, only sleep quality
      improves to a pre-mTBI level. Thus, recovery from mTBI-induced sleep disturbance
      occurs more rapidly than that of mTBI-induced depression and anxiety.

PMID- 24459041
TI  - Fluoride-induced apoptosis and expressions of caspase proteins in the kidney of
      carp (Cyprinus carpio).
AB  - The study was conducted to investigate oxidative stress, apoptosis, and protein
      expressions of caspase-3, 8, and 9 in kidney of the carp juveniles exposed to 0,
      40, 80, 120, and 160 mg L(-1) of fluoride (in the form of NaF) for 90 days. The
      results showed that dose- and time-dependent decrease of SOD and GSH and dose-
      and time-dependent increase of MDA were observed in the carp juveniles, which
      suggested that fluoride induced oxidative damage accompanied with morphological
      changes and significant apoptosis in fish exposed to fluoride, especially in the
      higher doses. Fluoride exposure also significantly elevated the protein
      expressions of caspase-3, 8, and 9. In conclusion, these results indicate that
      chronic exposure to fluoride causes oxidative stress, damages the kidney
      structure, and results in renal apoptosis by caspase-dependent pathway.

PMID- 24459042
TI  - Stillbirth: the heart of the matter.
AB  - We evaluated 2,083 cases within the Wisconsin Stillbirth Service Program (WiSSP)
      that had autopsy reports or ultrasound data relevant to the heart. Of these,
      167/1,782 (9.4%) stillbirths after 20 weeks and 11/301 (3.7%) miscarriages <20
      weeks had congenital heart disease (CHD). Cases were classified by type of heart
      defect and whether it related to cause of death. Among cardiac anomalies that
      contributed significantly to fetal death, 125/151 (83%) were associated with
      underlying conditions or syndromes, nearly half of which were chromosomal. The
      most common forms of CHD in stillborns were severe cyanotic lesions (3%), then
      ventricular (2.6%) and atrial (1.9%) septal defects. Compared to livebirths, this
      represents a shift toward more severe cardiac lesions, although all comparable
      categories, including non-lethal conditions such as atrial septal defect, are
      more common in stillbirths. Clinical cardiomyopathy was identified as cause of
      death in 1.2% of stillborns. Cardiomegaly, occurring in 26.7% of all cases and
      76.7% of infants born to diabetic mothers, may represent undiagnosed
      cardiomyopathy and/or may decrease fetal tolerance of hypoxia. In contrast, 78.5%
      of Turner syndrome infants, all <32 weeks, had small hearts. More attention to
      cardiac findings can lead to increased understanding of stillbirth causes. Based
      on our findings, we recommend chromosome studies on all stillbirths and close
      attention to the heart during second trimester ultrasounds, with chromosome
      studies offered if CHD is found. Consideration of heart size can result in
      prenatal identification of infants at risk for stillbirth, particularly large
      hearts in fetuses of diabetic mothers in the third trimester, which may identify
      fetal cardiomyopathy before it becomes life-threatening.

PMID- 24459043
TI  - Predicting Hyperhomocysteinemia by Methylenetetrahydrofolate Reductase C677T
      Polymorphism in Chinese Patients With Hypertension.
AB  - OBJECTIVE: To evaluate the performance of methylenetetrahydrofolate reductase
      (MTHFR) gene C677T polymorphism in predicting hyperhomocysteinemia (HHcy) in
      Chinese patients with hypertension. METHODS: We measured plasma total
      homocysteine tHcy level and C677T genotype in 1058 Chinese patients with
      hypertension from 4 previous studies. We used 10, 15, and 20 MUmol/L as cutoff
      values for the definition of mild, modest, and severe HHcy, respectively.
      Logistic models for HHcy were built from the study sample using the C677T
      genotype as well as age and gender as predictors. The receiver-operating
      characteristics of the models were evaluated. RESULTS: Our major findings are
      that (1) C677T TT genotype is consistently associated with a higher tHcy across
      the 4 studies, with an increase in size ranging from 38% to 68% in the 4 studies
      and 51% overall. The C677T polymorphism independently explained about 14% of the
      total variance of the normalized tHcy. (2) The TT genotype is associated with a
      large increase in odds ratio (OR) for HHcy. Overall, the multivariate-adjusted
      ORs for the TT genotype are 3.9 (95% confidence interval [CI]: 2.4-6.4), 6.5 (95%
      CI: 4.0-10.6), and 17.9 (95% CI: 8.4-38.1) for mild, modest, and severe HHcy,
      respectively. (3) Overall, the predicting performance increased with HHcy
      severity, with sensitivity improving from 31.0% for mild HHcy to 70.3% for severe
      HHcy, and with specificity slightly decreasing from 85.4% to 80.3%. Inclusion of
      gender and age as predictors significantly improves the sensitivity, especially
      for predicting mild HHcy. CONCLUSION: With an excellent sensitivity and a modest
      specificity, C677T could be a useful screening marker for severe HHcy.

PMID- 24459044
TI  - High-resolution metabolite imaging of light and dark treated retina using MALDI
      FTICR mass spectrometry.
AB  - MS imaging (MSI) is a valuable tool for diagnostics and systems biology studies,
      being a highly sensitive, label-free technique capable of providing comprehensive
      spatial distribution of different classes of biomolecules. The application of MSI
      to the study of endogenous compounds has received considerable attention because
      metabolites are the result of the interactions of a biosystem with its
      environment. MSI can therefore enhance understanding of disease mechanisms and
      elucidate mechanisms for biological variation. We present the in situ comparative
      metabolomics imaging data for analyses of light- and dark-treated retina using
      MALDI-FTICR. A wide variety of tissue metabolites were imaged at a high spatial
      resolution. These include nucleotides, central carbon metabolism pathway
      intermediates, 2-oxocarboxylic acid metabolism, oxidative phosphorylation,
      glycerophospholipid metabolism, and cysteine and methionine metabolites. The high
      lateral resolution enabled the differentiation of retinal layers, allowing
      determination of the spatial distributions of different endogenous compounds. A
      number of metabolites demonstrated differences between light and dark conditions.
      These findings add to the understanding of metabolic activity in the retina. 

PMID- 24459046
TI  - Impaired sperm chromatin integrity in obese mice.
AB  - An increased global prevalence of obesity coincides with an apparent decline in
      male sperm quality and a possible association between these pathologies has been
      suggested. In this study, we examined the effects of obesity on sperm chromatin
      integrity using two mouse models of obesity. In one group of mice, obesity was
      induced by a high-fat diet (HFD) (diet-induced obesity; DIO model), whereas in
      the other group, leptin deficiency was used to study the effects of obesity
      independently of the influence of dietary factors. Sperm chromatin integrity is
      recognized as an important measure of male infertility, and was analysed by the
      sperm chromatin structure assay. We found increased sperm DNA fragmentation in
      both groups of obese mice compared to lean mice, whereas the percentage of
      immature spermatozoa was not increased by obesity. The DIO model reflects the
      human condition more closely than the leptin-deficient model and was therefore
      selected for examination of the transcriptional response of a selection of marker
      genes in the testis by quantitative real-time PCR. The analysis of transcript
      levels of the selected testicular marker genes showed moderate, but significant,
      up-regulation of the Cyp2e1, Cyp19a1, Tnf and Pparg genes in DIO mice compared to
      lean mice. In conclusion, a clear positive correlation between body mass index
      and sperm DNA fragmentation was found in two mouse models of obesity. However,
      the variability in sperm DNA fragmentation within the two groups of obese animals
      was high. The observed changes in the transcript level of the marker genes
      suggest that there may be a local response in testicular cells to the HFD regimen
      with a potential impact on intratesticular signalling and spermatogenesis. 

PMID- 24459047
TI  - The smallest de novo deletion of 20q11.21-q11.23 in a girl with feeding problems,
      retinal dysplasia, and skeletal abnormalities.
AB  - We report on a de novo interstitial deletion of 20q11.21-q11.23 in a 2-year-old
      girl with a set of dysmorphic features, cleft palate, heart defect, severe
      feeding problems, failure to thrive, developmental delay, preaxial polydactyly
      (right thumb), and retinal dysplasia. Interstitial microdeletions of the long arm
      of chromosome 20 are rare. Exclusively rare are proximal microdeletions involving
      20q11-q12 region. Our patient is the fourth described so far and has the smallest
      deleted region 20q11.21-q11.23 of 5.7 Mb. The defined clinical phenotype of our
      patient is very similar to previously published cases and confirms the existence
      of retinal dysplasia and skeletal abnormalities as a part of phenotypic spectrum
      for deletion 20q11-q12. Description of four similar patients, including two
      almost identical, suggests a new distinct, phenotypicaly recognizable
      microdeletion syndrome associated with the loss of 20q11-q12 region.

PMID- 24459048
TI  - Use of the video-laryngoscope (GlideScope) in vocal fold injection medialization.

PMID- 24459049
TI  - Hydrosilylation induced by N->Si intramolecular coordination: spontaneous
      transformation of organosilanes into 1-aza-silole-type molecules in the absence
      of a catalyst.
AB  - Our attempts to synthesize the N->Si intramolecularly coordinated organosilanes
      Ph2 L(1) SiH (1 a), PhL(1) SiH2 (2 a), Ph2 L(2) SiH (3 a), and PhL(2) SiH2 (4 a)
      containing a CH=N imine group (in which L(1) is the C,N-chelating ligand {2
      [CH=N(C6 H3 -2,6-iPr2)]C6 H4}(-) and L(2) is {2-[CH=N(tBu)]C6 H4}(-)) yielded 1
      [2,6-bis(diisopropyl)phenyl]-2,2-diphenyl-1-aza-silole (1), 1-[2,6
      bis(diisopropyl)phenyl]-2-phenyl-2-hydrido-1-aza-silole (2), 1-tert-butyl-2,2
      diphenyl-1-aza-silole (3), and 1-tert-butyl-2-phenyl-2-hydrido-1-aza-silole (4),
      respectively. Isolated organosilicon amides 1-4 are an outcome of the spontaneous
      hydrosilylation of the CH=N imine moiety induced by N->Si intramolecular
      coordination. Compounds 1-4 were characterized by NMR spectroscopy and X-ray
      diffraction analysis. The geometries of organosilanes 1 a-4 a and their
      corresponding hydrosilylated products 1-4 were optimized and fully characterized
      at the B3LYP/6-31++G(d,p) level of theory. The molecular structure determination
      of 1-3 suggested the presence of a Si-N double bond. Natural bond orbital (NBO)
      analysis, however, shows a very strong donor-acceptor interaction between the
      lone pair of the nitrogen atom and the formal empty p orbital on the silicon and
      therefore, the calculations show that the Si-N bond is highly polarized pointing
      to a predominantly zwitterionic Si(+) N(-) bond in 1-4. Since compounds 1-4 are
      hydrosilylated products of 1 a-4 a, the free energies (DeltaG298), enthalpies
      (DeltaH298), and entropies (DeltaH298) were computed for the hydrosilylation
      reaction of 1 a-4 a with both B3LYP and B3LYP-D methods. On the basis of the very
      negative DeltaG298 values, the hydrosilylation reaction is highly exergonic and
      compounds 1 a-4 a are spontaneously transformed into 1-4 in the absence of a
      catalyst.

PMID- 24459050
TI  - Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti
      leukotrienes for chronic asthma.
AB  - BACKGROUND: Asthma patients who continue to experience symptoms despite taking
      regular inhaled corticosteroids (ICS) represent a management challenge. Long
      acting beta2-agonists (LABA) and anti-leukotrienes (LTRA) are two treatment
      options that could be considered as add-on therapy to ICS. OBJECTIVES: To compare
      the safety and efficacy of adding LABA versus LTRA to the treatment regimen for
      children and adults with asthma who remain symptomatic in spite of regular
      treatment with ICS. We specifically wished to examine the relative impact of the
      two agents on asthma exacerbations, lung function, symptoms, quality of life,
      adverse health events and withdrawals. SEARCH METHODS: We searched the Cochrane
      Airways Group Specialised Register until December 2012. We consulted reference
      lists of all included studies and contacted pharmaceutical manufacturers to ask
      about other published or unpublished studies. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) conducted in adults or children with
      recurrent asthma that was treated with ICS along with a fixed dose of a LABA or
      an LTRA for a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed the risk of bias of included studies and extracted
      data. We sought unpublished data and further details of study design when
      necessary. MAIN RESULTS: We included 18 RCTs (7208 participants), of which 16
      recruited adults and adolescents (6872) and two recruited children six to 17
      years of age (336) with asthma and significant reversibility to bronchodilator at
      baseline. Fourteen (79%) trials were of high methodological quality.The risk of
      exacerbations requiring systemic corticosteroids (primary outcome of the review)
      was significantly lower with the combination of LABA + ICS compared with LTRA +
      ICS-from 13% to 11% (eight studies, 5923 adults and 334 children; risk ratio (RR)
      0.87, 95% confidence interval (CI) 0.76 to 0.99; high-quality evidence). The
      number needed to treat for an additional beneficial outcome (NNTB) with LABA
      compared with LTRA to prevent one additional exacerbation over four to 102 weeks
      was 62 (95% CI 34 to 794). The choice of LTRA, the dose of ICS and the
      participants' age group did not significantly influence the magnitude of effect.
      Although results were inconclusive, the effect appeared stronger in trials that
      used a single device rather than two devices to administer ICS and LABA and in
      trials of less than 12 weeks' duration.The addition of LABA to ICS was associated
      with a statistically greater improvement from baseline in lung function, as well
      as in symptoms, rescue medication use and quality of life, although the latter
      effects were modest. LTRA was superior in the prevention of exercise-induced
      bronchospasm. More participants were satisfied with the combination of LABA + ICS
      than LTRA + ICS (three studies, 1625 adults; RR 1.12, 95% CI 1.04 to 1.20;
      moderate-quality evidence). The overall risk of withdrawal was significantly
      lower with LABA + ICS than with LTRA + ICS (13 studies, 6652 adults and 308
      children; RR 0.84, 95% CI 0.74 to 0.96; moderate-quality evidence). Although the
      risk of overall adverse events was equivalent between the two groups, the risk of
      serious adverse events (SAE) approached statistical significance in disfavour of
      LABA compared with LTRA (nine studies, 5658 adults and 630 children; RR 1.33, 95%
      CI 0.99 to 1.79; P value 0.06; moderate-quality evidence), with no apparent
      impact of participants' age group.The following adverse events were reported, but
      no significant differences were demonstrated between groups: headache (11
      studies, N = 6538); cardiovascular events (five studies, N = 5163), osteopenia
      and osteoporosis (two studies, N = 2963), adverse events (10 studies, N = 5977
      adults and 300 children). A significant difference in the risk of oral moniliasis
      was noted, but this represents a low occurrence rate. AUTHORS' CONCLUSIONS: In
      adults with asthma that is inadequately controlled by predominantly low-dose ICS
      with significant bronchodilator reversibility, the addition of LABA to ICS is
      modestly superior to the addition of LTRA in reducing oral corticosteroid-treated
      exacerbations, with an absolute reduction of two percentage points. Differences
      favouring LABA over LTRA as adjunct therapy were observed in lung function and,
      to a lesser extend, in rescue medication use, symptoms and quality of life. The
      lower overall withdrawal rate and the higher proportion of participants satisfied
      with their therapy indirectly favour the combination of LABA + ICS over LTRA +
      ICS. Evidence showed a slightly increased risk of SAE with LABA compared with
      LTRA, with an absolute increase of one percentage point. Our findings modestly
      support the use of a single inhaler for the delivery of both LABA and low- or
      medium-dose ICS. Because of the paucity of paediatric trials, we are unable to
      draw firm conclusions about the best adjunct therapy in children.

PMID- 24459055
TI  - Crystallization of DNA-capped gold nanoparticles in high-concentration, divalent
      salt environments.
AB  - The multiparametric nature of nanoparticle self-assembly makes it challenging to
      circumvent the instabilities that lead to aggregation and achieve crystallization
      under extreme conditions. By using non-base-pairing DNA as a model ligand instead
      of the typical base-pairing design for programmability, long-range 2D DNA-gold
      nanoparticle crystals can be obtained at extremely high salt concentrations and
      in a divalent salt environment. The interparticle spacings in these 2D
      nanoparticle crystals can be engineered and further tuned based on an empirical
      model incorporating the parameters of ligand length and ionic strength. 

PMID- 24459056
TI  - [ReF(6)](2-) : a robust module for the design of molecule-based magnetic
      materials.
AB  - A facile synthesis of the [ReF6 ](2-) ion and its use as a building block to
      synthesize magnetic systems are reported. Using dc and ac magnetic susceptibility
      measurements, INS and EPR spectroscopies, the magnetic properties of the isolated
      [ReF6 ](2-) unit in (PPh4 )2 [ReF6 ]?2 H2 O (1) have been fully studied including
      the slow relaxation of the magnetization observed below ca. 4 K. This slow
      dynamic is preserved for the one-dimensional coordination polymer [Zn(viz)4 (ReF6
      )]infinity (2, viz=1-vinylimidazole), demonstrating the irrelevance of low
      symmetry for such magnetization dynamics in systems with easy-plane-type
      anisotropy. The ability of fluoride to mediate significant exchange interactions
      is exemplified by the isostructural [Ni(viz)4 (ReF6 )]infinity (3) analogue in
      which the ferromagnetic Ni(II) -Re(IV) interaction (+10.8 cm(-1) ) dwarfs the
      coupling present in related cyanide-bridged systems. These results reveal [ReF6
      ](2-) to be an unique new module for the design of molecule-based magnetic
      materials. 

PMID- 24459057
TI  - Catalytic enantioselective amination of alcohols by the use of borrowing hydrogen
      methodology: cooperative catalysis by iridium and a chiral phosphoric acid.
AB  - The catalytic asymmetric reduction of ketimines has been explored extensively for
      the synthesis of chiral amines, with reductants ranging from Hantzsch esters,
      silanes, and formic acid to H2 gas. Alternatively, the amination of alcohols by
      the use of borrowing hydrogen methodology has proven a highly atom economical and
      green method for the production of amines without an external reductant, as the
      alcohol substrate serves as the H2 donor. A catalytic enantioselective variant of
      this process for the synthesis of chiral amines, however, was not known. We have
      examined various transition-metal complexes supported by chiral ligands known for
      asymmetric hydrogenation reactions, in combination with chiral Bronsted acids,
      which proved essential for the formation of the imine intermediate and the
      transfer-hydrogenation step. Our studies led to an asymmetric amination of
      alcohols to provide access to a wide range of chiral amines with good to
      excellent enantioselectivity. 

PMID- 24459058
TI  - Metal oxide-coated three-dimensional graphene prepared by the use of metal
      organic frameworks as precursors.
AB  - A simple method for the preparation of metal-oxide-coated three-dimensional (3D)
      graphene composites was developed. The metal-organic frameworks (MOFs) that
      served as the precursors of the metal oxides were first synthesized on the 3D
      graphene networks (3DGNs). The desired metal oxide/3DGN composites were then
      obtained by a two-step annealing process. As a proof-of-concept application, the
      obtained ZnO/3DGN and Fe2 O3 /3DGN materials were used in a photocatalytic
      reaction and a lithium-ion battery, respectively. We believe this method could be
      extended to the synthesis of other metal oxide/3DGN composites with 3D structures
      simply through the appropriate choice of specific MOFs as precursors. 

PMID- 24459059
TI  - Diastereoselective synthesis of open-chain secondary alkyllithium compounds and
      trapping reactions with electrophiles.
AB  - A practical stereoselective iodide-lithium exchange was used in the first general
      preparation of functionalized stereodefined acyclic secondary nonstabilized
      lithium reagents from the corresponding secondary alkyl iodides. These lithium
      reagents react with various electrophiles including carbon electrophiles with
      high retention of configuration. Kinetic data on the configurational stability of
      these acyclic alkyllithium reagents are given. This methodology offers a new
      entry to chiral synthons for the stereoselective synthesis of open-chain
      molecules. 

PMID- 24459060
TI  - Enzymatic conversion of flavonoids using bacterial chalcone isomerase and enoate
      reductase.
AB  - Flavonoids are a large group of plant secondary metabolites with a variety of
      biological properties and are therefore of interest to many scientists, as they
      can lead to industrially interesting intermediates. The anaerobic gut bacterium
      Eubacterium ramulus can catabolize flavonoids, but until now, the pathway has not
      been experimentally confirmed. In the present work, a chalcone isomerase (CHI)
      and an enoate reductase (ERED) could be identified through whole genome
      sequencing and gene motif search. These two enzymes were successfully cloned and
      expressed in Escherichia coli in their active form, even under aerobic
      conditions. The catabolic pathway of E. ramulus was confirmed by
      biotransformations of flavanones into dihydrochalcones. The engineered E. coli
      strain that expresses both enzymes was used for the conversion of several
      flavanones, underlining the applicability of this biocatalytic cascade reaction. 

PMID- 24459061
TI  - A chaperonin as protein nanoreactor for atom-transfer radical polymerization.
AB  - The group II chaperonin thermosome (THS) from the archaea Thermoplasma
      acidophilum is reported as nanoreactor for atom-transfer radical polymerization
      (ATRP). A copper catalyst was entrapped into the THS to confine the
      polymerization into this protein cage. THS possesses pores that are wide enough
      to release polymers into solution. The nanoreactor favorably influenced the
      polymerization of N-isopropyl acrylamide and poly(ethylene glycol)methylether
      acrylate. Narrowly dispersed polymers with polydispersity indices (PDIs) down to
      1.06 were obtained in the protein nanoreactor, while control reactions with a
      globular protein-catalyst conjugate only yielded polymers with PDIs above 1.84. 

PMID- 24459062
TI  - Venous coupler migration: a near miss.

PMID- 24459063
TI  - Effect of linagliptin compared with glimepiride on postprandial glucose
      metabolism, islet cell function and vascular function parameters in patients with
      type 2 diabetes mellitus receiving ongoing metformin treatment.
AB  - BACKGROUND: The goal of this study was to investigate the effects of linagliptin
      compared with glimepiride on alpha and beta cell function and several vascular
      biomarkers after a standardized test meal. METHODS: Thirty-nine patients on
      metformin alone (age, 64 +/- 7 years; duration of type 2 diabetes mellitus, 7.8
      +/- 4.5years, 27 male, 12 female; HbA1c , 57.2 +/- 6.9 mmol/mol; mean +/- SD)
      were randomized to receive linagliptin 5 mg (n = 19) or glimepiride (n = 20) for
      a study duration of 12 weeks. Glucagon-like peptide 1, blood glucose, insulin,
      intact proinsulin, glucagon, plasminogen activator inhibitor-1 (PAI-1), cyclic
      guanosinmonophosphat and asymetric dimethylarginin levels were measured in the
      fasting state and postprandial at 30-min intervals for a duration of 5 h. The
      areas under the curve (AUC0-300 min ) were calculated for group comparisons.
      RESULTS: HbA1c , fasting and postprandial glucose levels improved in both groups.
      An increase in postprandial insulin (22595 +/- 5984 pmol/L*min), postprandial
      intact proinsulin (1359 +/- 658 pmol/L*min), postprandial glucagon (317 +/- 1136
      pg/mL*min) and postprandial PAI-1 levels (863 +/- 467 ng/mL*min) could be
      observed during treatment with glimepiride, whereas treatment with linagliptin
      was associated with a decrease in postprandial insulin (-8007 +/- 4204
      pmol/L*min), intact proinsulin (-1771 +/- 426 pmol/L*min), postprandial glucagon
      (-1597 +/- 1831 pg/mL*min) and PAI-1 levels (-410 +/- 276 ng/mL*min).
      CONCLUSIONS: Despite an improvement in blood glucose control in both groups,
      linagliptin reduced postprandial insulin, proinsulin, glucagon and PAI-levels.
      These results indicate an improvement in postprandial alpha and beta cell
      function, as well as a reduced postprandial vascular risk profile during
      treatment with linagliptin.

PMID- 24459064
TI  - Genomic characterization of three urinary bladder cancer cell lines:
      understanding genomic types of urinary bladder cancer.
AB  - Several genomic regions are frequently altered and associated with the type,
      stage and progression of urinary bladder cancer (UBC). We present the
      characterization of 5637, T24 and HT1376 UBC cell lines by karyotyping,
      fluorescence in situ hybridization (FISH), array comparative genomic
      hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA)
      analysis. Some cytogenetic anomalies present in UBC were found in the three cell
      lines, such as chromosome 20 aneuploidy and the loss of 9p21. Some gene loci
      losses (e.g. CDKN2A) and gains (e.g. HRAS, BCL2L1 and PTPN1) were coincident
      across all cell lines. Although some significant heterogeneity and complexity
      were detected between them, their genomic profiles exhibited a similar pattern to
      UBC. We suggest that 5637 and HT1376 represent the E2F3/RB1 pathway due to
      amplification of 6p22.3, concomitant with loss of one copy of RB1 and mutation of
      the remaining copy. The HT1376 presented a 10q deletion involving PTEN region and
      no alteration of PIK3CA region which, in combination with the inactivation of
      TP53, bears more invasive and metastatic properties than 5637. The T24 belongs to
      the alternative pathway of FGFR3/CCND1 by presenting mutated HRAS and over
      represented CCND1. These cell lines cover the more frequent subtypes of UBC and
      are reliable models that can be used, as a group, in preclinical studies. 

PMID- 24459065
TI  - Monitoring of carcinoembryonic antigen levels is predictive of EGFR mutations and
      efficacy of EGFR-TKI in patients with lung adenocarcinoma.
AB  - For the detection of epidermal growth factor receptor (EGFR) mutations, tumor
      tissues may not always be available. Not all the patients harboring EGFR mutation
      have a clinical response after the treatment of epidermal growth factor receptor
      tyrosine kinase inhibitors (EGFR-TKI). EGFR mutations were detected in 70 cases
      of newly diagnosed non-smoking adenocarcinoma, and patients harboring EGFR
      mutations received EGFR-TKI treatment. The EGFR mutation status of these
      patients' blood was analyzed by amplification refractory mutation system (ARMS).
      The patients' carcinoembryonic antigen (CEA) levels were tested on the third,
      seventh, 15(th), and 30th days after EGFR-TKI treatment. Forty-four cases were
      found with EGFR mutations. EGFR mutation rate of CEA high-level group was
      significantly higher than low-level group (70.8% vs. 40.9%, P = 0.017).
      Multivariate analysis showed that high-level CEA is independently associated with
      EGFR gene mutation (P = 0.020, OR = 3.508, 95%CI, 1.223-10.059). The sensitivity
      of high CEA level and ARMS to predict EGFR mutation were 79.1% and 51.2%. We
      divided the patients who received EGFR-TKI treatment into three groups by the
      variation types of CEA. Univariate analysis showed that patients in descending
      type group have longer progression-free survival (P = 0.001, HR 6.981, 95%CI,
      2.534-19.237). Multivariate Cox proportional hazards model analyses shows the
      same result (P = 0.001, HR 9.82, 95%CI, 3.322-26.031). In conditions of the
      current technique, using high CEA level to predict EGFR mutations seems to be
      more sensitive than using EGFR mutations in plasma. The variation types of CEA
      level could help us to predict the efficacy of EGFR-TKI in patients harboring
      EGFR mutation within only 1 month of tyrosine kinase inhibitor therapy.

PMID- 24459066
TI  - Proteomic identification of potential prognostic biomarkers in resectable
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic cancer is a devastating disease with a mortality rate almost identical
      with its incidence. In this context, the investigation of the pancreatic cancer
      proteome has gained considerable attention because profiles of proteins may be
      able to identify disease states and progression more accurately. Therefore, our
      objective was to investigate the changes in the proteome of patients suffering
      from pancreatic ductal adenocarcinoma (PDAC) by a comprehensive quantitative
      approach. Comparative proteomic profiling by label-free LC-MS/MS analysis of nine
      matched pairs of tumor and nontumor pancreas samples was used to identify
      differences in protein levels characteristic for PDAC. In this analysis, 488
      proteins were quantified by at least two peptides of which 99 proteins displayed
      altered levels in PDAC (p < 0.01, fold change >1.3). Screening of data revealed a
      number of molecules that had already been related to PDAC such as galectin-1
      (LEG1), major vault protein, adenylyl cyclase-associated protein 1 (CAP1), but
      also a potential new prognostic biomarker prolargin (PRELP). The Kaplan-Meier
      survival analysis revealed a significant correlation of protein abundance of
      PRELP with postoperative survival of patients with PDAC. For selected proteins
      the findings were verified by targeted proteomics (SRM), validated by
      immunohistochemistry and Western blotting and their value as candidate biomarkers
      is discussed. 

PMID- 24459067
TI  - An unusual phenotype of X-linked developmental delay and extreme behavioral
      difficulties associated with a mutation in the EBP gene.
AB  - We report on a family in which four males over three generations are affected
      with X-linked recessive developmental delay, learning difficulties, severe
      behavioral difficulties and mild dysmorphic features. Plasma sterol analysis in
      three of the four affected males demonstrated increased concentrations of 8
      dehydrocholesterol (8-DHC) and cholest-8(9)-enol. All four affected males had a
      novel hemizygous missense mutation, p.W47R (c.139T>C), in EBP. Functional studies
      showed raised levels of cholest-8(9)-enol in patient's cultured fibroblast cells,
      which were suppressed when the cells were incubated with simvastatin. EBP encodes
      3beta-hydroxysteroid-delta8, delta7-isomerase, a key enzyme involved in the
      cholesterol biosynthesis pathway. Mutations in EBP have previously been
      associated with Conradi-Hunermann-Happle syndrome (CHH), an X-linked dominant
      disorder characterized by skeletal dysplasia, skin, and ocular abnormalities,
      which is usually lethal in males. Four previous reports describe X-linked
      recessive multiple anomaly syndromes associated with non-mosaic EBP mutations in
      males, two at the same amino acid position, p.W47C. This phenotype has previously
      been described as "MEND" syndrome (male EBP disorder with neurological defects).
      The family reported herein represent either a novel phenotype, or an expansion of
      the MEND phenotype, characterized by extreme behavioral difficulties and a
      scarcity of structural anomalies. Simvastatin therapy is being evaluated in two
      males from this family.

PMID- 24459068
TI  - Clickable, photodegradable hydrogels to dynamically modulate valvular
      interstitial cell phenotype.
AB  - Biophysical cues are widely recognized to influence cell phenotype. While this
      evidence was established using static substrates, there is growing interest in
      creating stimulus-responsive biomaterials that better recapitulate the dynamic
      extracellular matrix. Here, a clickable, photodegradable hydrogel substrate that
      allows the user to precisely control substrate elasticity and topography in situ
      is presented. The hydrogels are synthesized by reacting an 8-arm poly(ethylene
      glycol) alkyne with an azide-functionalized photodegradable crosslinker. The
      utility of this platform by exploiting its photoresponsive properties to modulate
      the phenotype of porcine aortic valvular interstitial cells (VICs) is
      demonstrated. First, VIC phenotype is monitored, in response to initial
      substratum modulus and static topographic cues. Higher modulus (E ~ 15 kPa)
      substrates induce higher levels of activation (~70% myofibroblasts) versus soft
      (E ~ 3 kPa) substrates (~20% myofibroblasts). Microtopographies that induce VIC
      alignment and elongation on low modulus substrates also stimulate activation.
      Finally, VIC phenotype is monitored in response to sequential in situ
      manipulations. The results illustrate that VIC activation on stiff surfaces (~70%
      myofibroblasts) can be partially reversed by reducing surface modulus (~30%
      myofibroblats) and subsequently re-activated by anisotropic topographies (~60%
      myofibroblasts). Such dynamic substrates afford unique opportunities to decipher
      the complex role of matrix cues on the plasticity of VIC activation.

PMID- 24459069
TI  - Hematopoietic stem cell transplantation in the leukodystrophies: a systematic
      review of the literature.
AB  - OBJECTIVE: The objective of this study is to systematically review the literature
      on worldwide numbers of leukodystrophy patients undergoing hematopoietic stem
      cell transplantation (HSCT) as well as the safety and efficacy of the procedure
      in this patient population. MATERIALS AND METHODS: A PubMed and EMBASE search up
      to June 2012 was conducted with a manual search of references from relevant
      articles. Selected studies were evaluated using internationally accepted
      criteria. The effect estimates of HSCT upon survival in early-stage disease
      versus late-stage disease were compared. RESULTS: One hundred and fifty-two
      studies qualified for inclusion and reported on a total of 689 patients. Study
      quality ranged from poor to good; no study was rated excellent. Small sample
      sizes limited most studies. Meta-analysis in a subset of larger studies indicates
      that transplantation in earlier stages of disease fairs better than in the late
      stages. Beyond survival, little longitudinal data on functional outcome is
      reported and neurological outcome is sparse. CONCLUSION: Further studies are
      needed to determine the neurological outcome following HSCT in the
      leukodystrophies. HSCT in the early stages of cerebral disease is still
      recommended for select leukodystrophies.

PMID- 24459070
TI  - Amyoplasia revisited.
AB  - Amyoplasia is a specific type and the most common form of arthrogryposis
      (multiple congenital contractures). It is a clinical diagnosis at this time. Care
      should be used making the diagnosis because of the implications for recurrence,
      natural history, associated anomalies, and both etiology and pathogenesis. We
      reviewed over 600 published reports and 2,500 individual records to identify the
      560 individuals reported here. Affected limbs had characteristic positions with
      fatty-fibrous replacement of muscle. Upper limb involvement was usually
      characterized by extended elbows. Lower limbs were held in various positions at
      birth; however, equinovarus positioning of feet was almost always present.
      Symmetric involvement was common. Among 560 affected individuals, subtypes were
      identified: four-limb symmetric involvement (331/560 = 55.9%), severe involvement
      (41/560 = 7.3%), three-limb involvement (27/560 = 4.8%), upper limb only
      Amyoplasia (ULA; 94/560 = 16.8%), and lower limb only Amyoplasia (LLA; 25/560 =
      15.5%). Discordant monozygotic twinning was increased, occurring in 6.6% (37/560;
      OR 10.9). A variety of additional anomalies were seen, attributed to apparent
      vascular compromise. Gastrointestinal vascular compromise-type anomalies were
      present in 9.1% (51/560), trunk muscle defects in another 2.7% (15/560), digit
      compromise in 12.1% (68/560), constriction rings in 4.3% (24/560), and perinatal
      long bone fractures in 10.5% (59/560). Although prenatal ultrasound became the
      standard of care in 1990, only about one quarter of affected pregnancies were
      diagnosed prenatally since 1990. Amyoplasia appears to be completely sporadic.
      Novel pathogenetic mechanisms for the congenital anomalies seen in Amyoplasia
      need to be identified.

PMID- 24459071
TI  - Quantitative EMG of external urethral sphincter in neurologically healthy men
      with prostate pathology.
AB  - INTRODUCTION: There are no data on quantitative electromyography (EMG) of the
      external urethral sphincter (EUS) in men. The aim of this study was to obtain
      reference data from a group of neurologically healthy continent men with prostate
      pathology using a standardized technique. METHODS: Sixty-six subjects without
      neurological disorders were included. Motor unit potential (MUP) and interference
      pattern (IP) analysis were performed using multi-MUP and turns/amplitude
      techniques, respectively. RESULTS: Of 66 patients, 51 (mean age, 65.17; SD, 6.70)
      had localized prostate cancer (PCa), and 15 (mean age 61.67, SD 6.25) had benign
      prostate hyperplasia (BPH). Descriptive MUP parameters and IP-clouds were
      obtained, respectively in the BPH and PCa groups. No group differences were
      found. CONCLUSIONS: This study provides quantitative EMG measures of EUS
      functionality in continent men with prostate pathology. The data could be used as
      reference values for patients undergoing prostate surgery to identify
      postoperative changes in EUS function possibly influencing continence.

PMID- 24459072
TI  - Reversible single-crystal-to-single-crystal photochemical formation and thermal
      cleavage of a cyclobutane ring.
AB  - A [2+2] cycloaddition reaction has been observed in a number of solids. The
      cyclobutane ring in a photodimerized material can be cleaved into olefins by UV
      light and heat. The high thermal stability of the metal-organic salt K2SDC (H2SDC
      = 4,4'-stilbenedicarboxylic acid) has been successfully utilized to investigate
      the reversible cleavage of a cyclobutane ring. The two polymorphs of K2SDC
      undergo reversible cyclobutane formation by UV light and cleavage by heat in
      cycles. Of these, one polymorph retains its single-crystal nature during the
      reversible processes. Polymorphs are known to show different physical properties
      and chemical reactivities. This work reveals that the retention of single-crystal
      nature is strongly associated with the packing of molecules, which is controlled
      by kinetics and thermodynamics. The photoemissive nature of the products makes
      this as a promising material for photoswitches and optical data storage devices.

PMID- 24459073
TI  - Emotional distress among adult survivors of childhood cancer.
AB  - PURPOSE: The purposes of this study were to estimate the prevalence of emotional
      distress in a large cohort of adult survivors of childhood cancer and to evaluate
      the interrelationship of risk factors including cancer-related late effects.
      METHODS: Adult survivors of childhood cancer (N = 1,863), median age of 32 years
      at follow-up, completed comprehensive medical evaluations. Clinically relevant
      emotional distress was assessed using the Brief Symptom Inventory 18 and was
      defined as T-scores >=63. Odds ratios (ORs) and 95% confidence intervals (CIs)
      were calculated using multivariable logistic regression models to identify risk
      factors for distress. Path analysis was used to examine associations among
      identified risk factors. RESULTS: Elevated global distress was reported by 15.1%
      of survivors. Cancer-related pain was associated with elevated distress (OR 8.72;
      95% CI, 5.32-14.31). Survivors who reported moderate learning or memory problems
      were more likely to have elevated distress than survivors who reported no
      learning or memory problems (OR 3.27; 95% CI, 2.17-4.93). Path analysis implied
      that cancer-related pain has a direct effect on distress symptoms and an indirect
      effect through socioeconomic status and learning or memory problems. Similar
      results were observed for learning or memory problems. CONCLUSIONS: Childhood
      cancer-related morbidities including pain and learning or memory problems appear
      to be directly and indirectly associated with elevated distress symptoms decades
      after treatment. Understanding these associations may help inform intervention
      targets for survivors of childhood cancer experiencing symptoms of distress.
      IMPLICATIONS FOR CANCER SURVIVORS: A subset of long-term childhood cancer
      survivors experience significant emotional distress. Physical and cognitive late
      effects may contribute to these symptoms.

PMID- 24459077
TI  - Sustainable development in an N-rich/n-poor world.
AB  - Sustainable development requires that per capita inclusive wealth-produced,
      human, and natural capital-does not decline over time. We investigate the impact
      of changes in nitrogen on inclusive wealth. There are two sides to the nitrogen
      problem. Excess use of nitrogen in some places gives rise to N-pollution, which
      can cause environmental damage. Insufficient replacement of nitrogen in other
      places gives rise to N-depletion, or loss of nutrient stocks. Neither is
      explicitly accounted for in current wealth measures, but both affect wealth. We
      calculate an index of net N-replacement, and investigate its relationship to
      wealth. In countries with low levels of relative N-loss, we find that the
      uncompensated loss of soil nitrogen in poorer countries is associated with
      declining rates of growth of inclusive per capita wealth. What is less intuitive
      is that increasing fertilizer application in both rich and poor countries can
      increase per capita inclusive wealth. 

PMID- 24459076
TI  - Multiecho acquisition of O-space data.
AB  - PURPOSE: Nonlinear gradient encoding methods, such as O-Space imaging, have been
      shown to provide good images from very few echoes. Acquiring data in a train of
      spin or gradient echoes is a very flexible way to further speed acquisition time.
      However, combining these strategies presents significant challenges, both in
      terms of the contrast and artifacts. We present strategies in both pulse sequence
      design and image processing to mitigate these effects. THEORY AND METHODS: The
      three strategies include a new echo ordering that takes into account the unique
      way that O-Space samples the k-space of the image; a new postprocessing filter
      that allows tuning of T2-weighting by emphasizing the contribution of low
      frequency spatial information at selectable points in space and time; and an
      offset between linear and nonlinear gradients that makes the central point of
      each echo unique. RESULTS: Simulations indicate that these strategies mitigate
      artifacts introduced by T2 (or T2*) decay and produce contrast that reflects
      relaxation at a given echo time. CONCLUSION: Turbo spin echo O-Space is
      theoretically feasible, and the greater undersampling should make it possible to
      use shorter echo trains for a given scan time.

PMID- 24459078
TI  - Perkin's and Caro's mauveine in Queen Victoria's lilac postage stamps: a chemical
      analysis.
AB  - Mauveine, a chemical icon, is no longer commercially available. If nowadays one
      wanted to have a sample of the original Perkin, or Caro, mauveine, and see its
      colour, where would one find it? The answer is on UK Victorian 6d postage stamps
      from 1867-1880. This was found from a comparison with historical samples of
      mauveine, from both William Perkin and a Heinrich Caro sample (here analysed for
      the first time). These have distinctly different compositions and this was used
      to identify the origin of mauveine in the postage stamps, with evidence found for
      mauveine made by both Perkin's and Caro's synthesis. 

PMID- 24459080
TI  - EEG for children with complex febrile seizures.
AB  - BACKGROUND: Febrile seizures can be classified as simple or complex. Complex
      febrile seizures are associated with fever that lasts longer than 15 minutes,
      occur more than once within 24 hours and are confined to one side of the child's
      body. It is common in some countries for doctors to recommend an
      electroencephalograph (EEG) for children with complex febrile seizures. A limited
      evidence base is available to support the use of EEG and its timing after complex
      febrile seizures among children. OBJECTIVES: To assess the use of EEG and its
      timing after complex febrile seizures in children younger than five years of age.
      SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (17
      October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 9, 2013), MEDLINE (17 October 2013) and the Clinical
      Trial Registry (ClinicalTrials.gov (17 October 2013)). We applied no language
      restrictions. SELECTION CRITERIA: All randomised controlled trials (RCTs) that
      examined the utility of an EEG and its timing after complex febrile seizures in
      children. DATA COLLECTION AND ANALYSIS: Review authors selected and retrieved the
      articles and independently assessed which articles should be included.
      Disagreements were resolved by discussion and by consultation with the Cochrane
      Epilepsy Group. We applied standard methodological procedures expected by The
      Cochrane Colloboration. MAIN RESULTS: Of 33 potentially eligible studies, no RCTs
      met the inclusion criteria. AUTHORS' CONCLUSIONS: We found no RCTs as evidence to
      support or refute the use of EEG and its timing after complex febrile seizures
      among children. A randomised controlled trial can be planned in such a way that
      participants are randomly assigned to the EEG group and to the non-EEG group with
      sufficient sample size.

PMID- 24459079
TI  - Complete posttranslational modification mapping of pathogenic Neisseria
      meningitidis pilins requires top-down mass spectrometry.
AB  - In pathogenic bacteria, posttranslationally modified proteins have been found to
      promote bacterial survival, replication, and evasion from the host immune system.
      In the human pathogen Neisseria meningitidis, the protein PilE (15-18 kDa) is the
      major building block of type IV pili, extracellular filamentous organelles that
      play a major role in mediating pathogenesis. Previous reports have shown that
      PilE can be expressed as a number of different proteoforms, each harboring its
      own set of PTMs and that specific proteoforms are key in promoting bacterial
      virulence. Efficient tools that allow complete PTM mapping of proteins involved
      in bacterial infection are therefore strongly needed. As we show in this study, a
      simple combination of mass profiling and bottom-up proteomics is fundamentally
      unable to achieve this goal when more than two proteoforms are present
      simultaneously. In a N. meningitidis strain isolated from a patient with
      meningitis, mass profiling revealed the presence of four major proteoforms of
      PilE, in a 1:1:1:1 ratio. Due to the complexity of the sample, a top-down
      approach was required to achieve complete PTM mapping for all four proteoforms,
      highlighting an unprecedented extent of glycosylation. Top-down MS therefore
      appears to be a promising tool for the analysis of highly posttranslationally
      modified proteins involved in bacterial virulence. 

PMID- 24459082
TI  - Treatment of hyperglycaemia in newly diagnosed diabetic patients is associated
      with a reduction in oxidative stress and improvement in beta-cell function.
AB  - BACKGROUND: There exist several reports demonstrating enhancement in oxidative
      stress in diabetic patients; however, serial and comprehensive measurement of
      oxidative stress parameters in newly diagnosed diabetic patients is not yet
      reported. We measured the oxidative stress parameters in diabetic patients
      serially from the time of diagnosis and after starting treatment to study their
      association with glycaemia, insulin resistance and beta-cell function. METHODS:
      Fifty-four newly diagnosed diabetic patients were studied at diagnosis and 4 and
      8 weeks after initiating anti-hyperglycaemic treatment. Oxidative stress
      parameters included activity of antioxidant enzymes, concentration of antioxidant
      molecules and damage markers. Oxidative stress score was computed as a collective
      measure of oxidative stress to interpret total oxidative stress state.
      Association of changing glucose levels with changing oxidative stress parameters
      over 8 weeks and association of oxidative stress score with insulin resistance
      and beta-cell function was analysed by homeostasis model assessment (HOMA-IR and
      HOMA-beta, respectively). RESULTS: Eight weeks of treatment improved HbA1C from
      9.8 +/- 2.1 to 7.7 +/- 1.0%. There was a significant increase in oxidative stress
      in diabetic patients [23.8 (95% CI 20.0, 27.6)] compared with non-diabetic
      subjects [-1.2 (-3.4, 0.9)] (p < 0.001). Non-diabetic subjects showed a stable
      status over 8 weeks. Improvement in hyperglycaemia in diabetic patients was
      associated with an improvement in oxidative stress parameters irrespective of the
      anti-diabetic treatment received. Oxidative stress score fell after 8 weeks and
      was significantly associated with an improvement in HOMA-beta (standardized beta
      = -0.38, p < 0.01) but not with HOMA-IR. CONCLUSIONS: Controlling hyperglycaemia
      in diabetic patients alleviates oxidative stress within 8 weeks of treatment, and
      improvement in oxidative stress parameters was related to an improved beta-cell
      function.

PMID- 24459083
TI  - Microfluidics expands the zebrafish potentials in pharmaceutically relevant
      screening.
AB  - The objective of this study is to enlarge the impact of microfluidics on the
      pharmaceutical industry by highlighting the reported scientific work on the
      synergistic relationship between zebrafish and microfluidics, and furthering that
      effort to shed light on how microfluidics can facilitate the use of zebrafish as
      a gene screening tool. Zebrafish is ranked the third most important animal model
      after rats and mice, according to a National Institutes of Health (NIH)
      announcement in 2003. It has become a staple for scientists to examine and
      subsequently begin to unravel the mystery of human diseases, and is increasingly
      used in toxicological studies for new drug development. The unique
      characteristics that this tiny fish possesses, including rapid growth rate,
      prodigious numbers of offspring, and eggs that develop outside the body, make it
      an invaluable genetic tool. Evidently, these advantages can be broadened with the
      addition of a properly designed microfluidic circuit. By means of the presented
      illustrations and demonstrated applications, the goal is to spark interest in the
      development of more novel microfluidic platform designs that can leverage the
      attributes of zebrafish and quickly come to commercial fruition. 

PMID- 24459084
TI  - Molecular characterization of distal 4q duplication in two patients using
      oligonucleotide array-based comparative genomic hybridization (oaCGH) analysis.
AB  - Pure/direct duplications on the long arm of chromosome 4 represent an infrequent
      chromosomal finding. Description of clinical findings in 30 patients has resulted
      in defining the 4q-associated phenotype. However, such duplications have not been
      molecularly or genomically characterized yet, limiting genotype-phenotype
      correlation. We report on the first two patients with a duplication involving the
      distal third of 4q that are characterized molecularly and genomically. Clinical
      features in our patients typical of 4q duplication syndrome included mild
      intellectual disability, cranial malformation, minor facial dysmorphism, and
      digital anomaly. Duplication of the segment 4q33-4q34, appears to be the critical
      region resulting in the phenotype associated with 4q duplication syndrome. The
      genes GLRA3, GMP6A that are invovled in neurogenesis and HAND2 in craniofacial
      development, within the duplicated region of 4q, may play a key role in the
      clinical phenotype. As more reporting on molecular characterization of 4q
      duplication becomes available, the role of these underlying genes may become
      clearer.

PMID- 24459081
TI  - Neurological aspects of human parvovirus B19 infection: a systematic review.
AB  - Parvovirus B19 has been linked with various clinical syndromes including
      neurological manifestations. However, its role in the latter remains not
      completely understood. Although the last 10 years witnessed a surge of case
      reports on B19-associated neurological aspects, the literature data remains
      scattered and heterogeneous, and epidemiological information on the incidence of
      B19-associated neurological aspects cannot be accurately extrapolated. The aim of
      this review is to identify the characteristics of cases of B19-associated
      neurological manifestations. A computerized systematic review of existing
      literature concerning cases of B19-related neurological aspects revealed 89
      articles describing 129 patients; 79 (61.2%) were associated with CNS
      manifestations, 41 (31.8%) were associated with peripheral nervous system
      manifestations, and 9 (7.0%) were linked with myalgic encephalomyelitis. The
      majority of the cases (50/129) had encephalitis. Clinical characteristic features
      of these cases were analyzed, and possible pathological mechanisms were also
      described. In conclusion, B19 should be included in differential diagnosis of
      encephalitic syndromes of unknown etiology in all age groups. Diagnosis should
      rely on investigation of anti-B19 IgM antibodies and detection of B19 DNA in
      serum or CSF. Treatment of severe cases might benefit from a combined regime of
      intravenous immunoglobulins and steroids. To confirm these outcomes, goal
      targeted studies are recommended to exactly identify epidemiological scenarios
      and explore potential pathogenic mechanisms of these complications. Performing
      retrospective and prospective and multicenter studies concerning B19 and
      neurological aspects in general, and B19 and encephalitic syndromes in
      particular, are required.

PMID- 24459085
TI  - Hybrid phospholipid bilayer coatings for separations of cationic proteins in
      capillary zone electrophoresis.
AB  - Protein separations in CZE suffer from nonspecific adsorption of analytes to the
      capillary surface. Semipermanent phospholipid bilayers have been used to minimize
      adsorption, but must be regenerated regularly to ensure reproducibility. We
      investigated the formation, characterization, and use of hybrid phospholipid
      bilayers (HPBs) as more stable biosurfactant capillary coatings for CZE protein
      separations. HPBs are formed by covalently modifying a support with a hydrophobic
      monolayer onto which a self-assembled lipid monolayer is deposited. Monolayers
      prepared in capillaries using 3-cyanopropyldimethylchlorosilane (CPDCS) or n
      octyldimethylchlorosilane (ODCS) yielded hydrophobic surfaces with lowered
      surface free energies of 6.0 +/- 0.3 or 0.2 +/- 0.1 mJ m(-2) , respectively,
      compared to 17 +/- 1 mJ m(-2) for bare silica capillaries. HPBs were formed by
      subsequently fusing vesicles comprised of 1,2-dilauroyl-sn-glycero-3
      phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine to CPDCS- or ODCS
      modified capillaries. The resultant HPB coatings shielded the capillary surface
      and yielded reduced electroosmotic mobility (1.3-1.9 * 10(-4) cm(2) V(-1) s(-1) )
      compared to CPDCS- and ODCS-modified or bare capillaries (3.6 +/- 0.2 * 10(-4)
      cm(2) V(-1) s(-1) , 4.8 +/- 0.4 * 10(-4) cm(2) V(-1) s(-1) , and 6.0 +/- 0.2 *
      10(-4) cm(2) V(-1) s(-1) , respectively), with increased stability compared to
      phospholipid bilayer coatings. HPB-coated capillaries yielded reproducible
      protein migration times (RSD <= 3.6%, n >= 6) with separation efficiencies as
      high as 200 000 plates/m.

PMID- 24459086
TI  - A novel WTX mutation in a female patient with osteopathia striata with cranial
      sclerosis and hepatoblastoma.
AB  - Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant
      sclerosing bone dysplasia. Typically affected females show macrocephaly,
      characteristic facial appearance, cleft palate, mild learning difficulties,
      hearing loss, sclerosis of the long bones and skull, and longitudinal striations
      visible on radiographs of the long bones, pelvis and scapulae. Typically affected
      males usually die at the fetal or early neonatal stage. Because of its variable
      expressivity, which ranges from asymptomatic to fetal death, clinical diagnosis
      of OSCS can be difficult. Here, we identify a unique female patient presenting
      with severe macrocephaly, characteristic facial appearance, developmental delay,
      and hepatoblastoma. Exome sequencing identified a novel de novo nonsense mutation
      (c.1045C>T, p.Glu349*) in the WTX gene associated with OSCS. The OSCS diagnosis
      was confirmed in this patient based on the hallmark appearance of longitudinal
      striations in long bones when viewed by X-ray. WTX is also known as a tumor
      suppressor gene, and somatic mutations in that gene have been identified in Wilms
      tumors. In addition to this patient, although two patients with OSCS have been
      reported to have colorectal cancer or ovarian cancer, Wilms tumor has never been
      reported in association with this disorder. Tumor susceptibility in patients with
      OSCS is discussed.

PMID- 24459087
TI  - Nitrogen-doped carbon nanosheets with size-defined mesopores as highly efficient
      metal-free catalyst for the oxygen reduction reaction.
AB  - Nitrogen-doped carbon nanosheets (NDCN) with size-defined mesopores are reported
      as highly efficient metal-free catalyst for the oxygen reduction reaction (ORR).
      A uniform and tunable mesoporous structure of NDCN is prepared using a templating
      approach. Such controlled mesoporous structure in the NDCN exerts an essential
      influence on the electrocatalytic performance in both alkaline and acidic media
      for the ORR. The NDCN catalyst with a pore diameter of 22 nm exhibits a more
      positive ORR onset potential than that of Pt/C (-0.01 V vs. -0.02 V) and a high
      diffusion-limited current approaching that of Pt/C (5.45 vs. 5.78 mA cm(-2) ) in
      alkaline medium. Moreover, the catalyst shows pronounced electrocatalytic
      activity and long-term stability towards the ORR under acidic conditions. The
      unique planar mesoporous shells of the NDCN provide exposed highly electroactive
      and stable catalytic sites, which boost the electrocatalytic activity of metal
      free NDCN catalyst. 

PMID- 24459088
TI  - New phase-based B1 mapping method using two-dimensional spin-echo imaging with
      hyperbolic secant pulses.
AB  - PURPOSE: To propose a new phase-based B1-mapping method that exploits phase
      information created by hyperbolic secant (HS) pulses in conventional 2D spin-echo
      imaging. METHODS: In this B1-mapping method, HS pulses are used to accomplish
      pi/2 excitation and pi refocusing in standard multislice spin-echo imaging. When
      setting the ratio of pulse lengths of the pi/2 and pi HS pulses to 2:1, the spin
      echo phase is independent of offset frequency and varies as a function of B1
      strength. To eliminate undesired phase accumulations induced by unknown factors
      other than the B1 strength, two spin-echo images are acquired using HS pulses
      applied with opposite frequency-sweep directions, and the resulting phase images
      are subtracted from each other. To demonstrate the performance of the proposed
      method, phantom and in vivo experiments were performed using a surface coil and a
      volume coil. RESULTS: The B1 maps obtained by using the proposed method were in
      accordance with the B1 maps obtained using previous methods in both phantom and
      in vivo experiments. CONCLUSION: The proposed method is easy to implement without
      any sequence modification, is insensitive to B0 inhomogeneity and chemical shift,
      and is robust in a reasonably wide range of B1 field strength.

PMID- 24459090
TI  - Coordination chemistry of cyclopropenylidene-stabilized phosphenium cations:
      synthesis and reactivity of Pd and Pt complexes.
AB  - A straightforward synthesis of cyclopropenylidene-stabilized phosphenium cations
      1 a-g through the reaction of [(iPr2N)2C3(+)Cl]BF4 with secondary phosphines is
      described. Their donor ability was evaluated by analysis of the CO stretching
      frequency in Rh complexes [RhCl(CO)L2](BF4)2 and electrochemical methods. The
      cyclopropenium ring induces a phosphite-type behavior that can be tuned by the
      other two substituents attached to the phosphorus atom. Despite of the positive
      charge that they bear, phosphenium cations 1 a-g still act as two-electron donor
      ligands, forming adducts with Pd(II) and Pt(II) precursors. Conversely, in the
      presence of Pd(0) species, an oxidative insertion of the Pd atom into the
      Ccarbene-phosphorus bond takes place, providing dimeric structures in which each
      Pd atom is bonded to a cyclopropenyl carbene while two dialkyl/diaryl phosphide
      ligands serve as bridges between the two Pd centers. The catalytic performance of
      the resulting library of Pt(II) complexes was tested; all of the cationic
      phosphines accelerated the prototype 6-endo-dig cyclization of 2-ethynyl-1,1'
      biphenyl to afford pentahelicene. The best ligand 1 g was used in the synthesis
      of two natural products, chrysotoxene and epimedoicarisoside A.

PMID- 24459089
TI  - Gene mutations in primary ciliary dyskinesia related to otitis media.
AB  - Otitis media with effusion (OME) is the most common cause of conductive hearing
      loss in children and is strongly associated with primary ciliary dyskinesia
      (PCD). Approximately half of the children with PCD require otolaryngology care,
      posing a major problem in this population. Early diagnosis of PCD is critical in
      these patients to minimise the collateral damage related to OME. The current gold
      standard for PCD diagnosis requires determining ciliary structure defects by
      transmission electron microscopy (TEM) or clearly documenting ciliary dysfunction
      via digital high-speed video microscopy (DHSV). Although both techniques are
      useful for PCD diagnosis, they have limitations and need to be supported by new
      methodologies, including genetic analysis of genes related to PCD. In this
      article, we review classical and recently associated mutations related to ciliary
      alterations leading to PCD, which can be useful for early diagnosis of the
      disease and subsequent early management of OME. 

PMID- 24459091
TI  - Quadrature transmit coil for breast imaging at 7 tesla using forced current
      excitation for improved homogeneity.
AB  - PURPOSE: To demonstrate the use of forced current excitation (FCE) to create
      homogeneous excitation of the breast at 7 tesla, insensitive to the effects of
      asymmetries in the electrical environment. MATERIALS AND METHODS: FCE was
      implemented on two breast coils: one for quadrature (1) H imaging and one for
      proton-decoupled (13) C spectroscopy. Both were a Helmholtz-saddle combination,
      with the saddle tuned to 298 MHz for imaging and 75 MHz for spectroscopy. Bench
      measurements were acquired to demonstrate the ability to force equal currents on
      elements in the presence of asymmetric loading to improve homogeneity. Modeling
      and temperature measurements were conducted per safety protocol. B1 mapping,
      imaging, and proton-decoupled (13) C spectroscopy were demonstrated in vivo.
      RESULTS: Using FCE to ensure balanced currents on elements enabled
      straightforward tuning and maintaining of isolation between quadrature elements
      of the coil. Modeling and bench measurements confirmed homogeneity of the field,
      which resulted in images with excellent fat suppression and in broadband proton
      decoupled carbon-13 spectra. CONCLUSION: FCE is a straightforward approach to
      ensure equal currents on multiple coil elements and a homogeneous excitation
      field, insensitive to the effects of asymmetries in the electrical environment.
      This enabled effective breast imaging and proton-decoupled carbon-13 spectroscopy
      at 7T.

PMID- 24459092
TI  - Molecular tweezers targeting transthyretin amyloidosis.
AB  - Transthyretin (TTR) amyloidoses comprise a wide spectrum of acquired and
      hereditary diseases triggered by extracellular deposition of toxic TTR aggregates
      in various organs. Despite recent advances regarding the elucidation of the
      molecular mechanisms underlying TTR misfolding and pathogenic self-assembly,
      there is still no effective therapy for treatment of these fatal disorders.
      Recently, the "molecular tweezers", CLR01, has been reported to inhibit self
      assembly and toxicity of different amyloidogenic proteins in vitro, including
      TTR, by interfering with hydrophobic and electrostatic interactions known to play
      an important role in the aggregation process. In addition, CLR01 showed
      therapeutic effects in animal models of Alzheimer's disease and Parkinson's
      disease. Here, we assessed the ability of CLR01 to modulate TTR misfolding and
      aggregation in cell culture and in an animal model. In cell culture assays we
      found that CLR01 inhibited TTR oligomerization in the conditioned medium and
      alleviated TTR-induced neurotoxicity by redirecting TTR aggregation into the
      formation of innocuous assemblies. To determine whether CLR01 was effective in
      vivo, we tested the compound in mice expressing TTR V30M, a model of familial
      amyloidotic polyneuropathy, which recapitulates the main pathological features of
      the human disease. Immunohistochemical and Western blot analyses showed a
      significant decrease in TTR burden in the gastrointestinal tract and the
      peripheral nervous system in mice treated with CLR01, with a concomitant
      reduction in aggregate-induced endoplasmic reticulum stress response, protein
      oxidation, and apoptosis. Taken together, our preclinical data suggest that CLR01
      is a promising lead compound for development of innovative, disease-modifying
      therapy for TTR amyloidosis. 

PMID- 24459093
TI  - Autocrine C-peptide mechanism underlying INS1 beta cell adaptation to oxidative
      stress.
AB  - BACKGROUND: Excessive generation of reactive oxygen species (ROS) causing
      oxidative stress plays a major role in the pathogenesis of diabetes by inducing
      beta cell secretory dysfunction and apoptosis. Recent evidence has shown that C
      peptide, produced by beta cells and co-secreted with insulin in the circulation
      of healthy individuals, decreases ROS and prevents apoptosis in dysfunctional
      vascular endothelial cells. In this study, we tested the hypothesis that an
      autocrine activity of C-peptide similarly decreases ROS when INS1 beta cells are
      exposed to stressful conditions of diabetes. METHODS: Reactive oxygen species and
      apoptosis were induced in INS1 beta cells pretreated with C-peptide by either 22
      mM glucose or 100 MUM hydrogen peroxide (H2 O2 ). To test C-peptide's autocrine
      activity, endogenous C-peptide secretion was inhibited by the KATP channel opener
      diazoxide and H2 O2 -induced ROS assayed after addition of either exogenous C
      peptide or the secretagogue glibenclamide. In similar experiments, extracellular
      potassium, which depolarizes the membrane otherwise hyperpolarized by diazoxide,
      was used to induce endogenous C-peptide secretion. ROS was measured using the
      cell-permeant dye chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2 
      DCFDA). Insulin secretion and apoptosis were assayed by enzyme-linked
      immunosorbent assay. RESULTS: C-peptide significantly decreased high glucose
      induced and H2 O2 -induced ROS and prevented apoptosis of INS1 beta cells.
      Diazoxide significantly increased H2 O2 -induced ROS, which was reversed by
      exogenous C-peptide or glibenclamide or potassium chloride. CONCLUSIONS: These
      findings demonstrate an autocrine C-peptide mechanism in which C-peptide is
      bioactive on INS1 beta cells exposed to stressful conditions and might function
      as a natural antioxidant to limit beta cell dysfunction and loss contributing to
      diabetes.

PMID- 24459095
TI  - Amyoplasia involving only the upper limbs or only involving the lower limbs with
      review of the relevant differential diagnoses.
AB  - Of individuals with Amyoplasia, 16.8% (94/560) involve only the upper limbs
      (Upper Limb Amyoplasia-ULA) and 15.2% (85/560) involve only the lower limbs
      (Lower Limb Amyoplasia-LLA). The accompanying paper deals with other forms of
      Amyoplasia [Hall et al., 2013] and discusses etiology. An excess of one of
      monozygotic (MZ) twins is seen in both groups (ULA 4/94 (4.3%), LLA 5/85 (5.9%)),
      gastrointestinal (GI) abnormalities thought to be of vascular origin (bowel
      atresia and gastroschisis) (ULA 16/94 (17%), LLA 4/85 (4.7%)), small or partial
      absence of digits (ULA 6/94 (6.2%), LLA 8/85 (9.4%)), and umbilical cord wrapping
      around the limbs at birth (ULA 3/94 (3.2%), LLA 7/85 (8.2%)) (severe enough to
      leave a permanent groove). Pregnancy complications occurred in 42/60 (70%) of ULA
      and 36/54 (67%) of LLA. Prenatal diagnosis, after ultrasound usage became
      routine, occurred in only 7/25 (28%) of ULA and 5/12 (12%) of LLA. This series
      may represent an over estimate of the complications and associations occurring in
      ULA and LLA. Differential diagnoses separating LLA from the genetic forms of
      "lower limb only" arthrogryposis and ULA from "upper limb only" genetic forms of
      arthrogryposis and Erb's palsy is provided.

PMID- 24459096
TI  - Nutation frequency modulation on NMR signal of nuclear spins in chemical exchange
      with solvent water under the BEST conditions.
AB  - Solvent exchange properties of protein backbone amide protons provide valuable
      residue-specific information on protein solvent accessibility, structure
      stability and flexibility and hence are of significant interest in structural
      biology. NMR has served as a unique means for the characterization of chemical
      exchange including proton amide exchange with solvent water at residue-specific
      levels across a broad range of exchange rates. One of the methods used for the
      characterization of protein backbone amide exchange by NMR involves the use of
      progressive selective irradiation of the water resonance. Here, we report the
      experimental observation of the nutation frequency (strength of RF field used for
      the irradiation of water resonance) modulation on amide proton signals for those
      in exchange with the solvent water under the band-selective excitation short
      transient (BEST) conditions. Compared with conventional saturation transfer of
      water magnetization experiments, this nutation frequency modulation observed on
      signal of nuclear spins under the BEST conditions potentially offers a quick
      identification of protein backbone amides in rapid exchange with solvent water.

PMID- 24459097
TI  - Spatial blockage of ionic current for electrophoretic translocation of DNA
      through a graphene nanopore.
AB  - Graphene nanopore has been promising the ultra-high resolution for DNA sequencing
      due to the atomic thickness and excellent electronic properties of the graphene
      monolayer. The dynamical translocation phenomena and/or behaviors underneath the
      blocked ionic current, however, have not been well unveiled to date for the
      translocation of DNA electrophoretically through a graphene nanopore. In this
      report, the assessment on the sensitivity of ionic current to instantaneous
      statuses of DNA in a 2.4 nm graphene nanopore was carried out based on the all
      atom molecular dynamics simulations. By filtering out the thermal noise of ionic
      current, the instantaneous conformational variations of DNA in a graphene
      nanopore have been unveiled from the fluctuations of ionic current, because of
      the spatial blockage effect of DNA against ionic current. Interestingly, the
      neighborhood effect of DNA against ionic current was also observed within a
      distance of 1.5 nm nearby the graphene nanopore, suggesting the further precise
      control for DNA translocation through a graphene nanopore in gene sequencing.
      Moreover, the sensitivity of the blocked ionic current toward the instantaneous
      conformations of DNA in a graphene nanopore demonstrates the great potential of
      graphene nanopores in the dynamics analysis of single molecules.

PMID- 24459094
TI  - Small-molecule control of intracellular protein levels through modulation of the
      ubiquitin proteasome system.
AB  - Traditionally, biological probes and drugs have targeted the activities of
      proteins (such as enzymes and receptors) that can be readily controlled by small
      molecules. The remaining majority of the proteome has been deemed "undruggable".
      By using small-molecule modulators of the ubiquitin proteasome, protein levels,
      rather than protein activity, can be targeted instead, thus increasing the number
      of druggable targets. Whereas targeting of the proteasome itself can lead to a
      global increase in protein levels, the targeting of other components of the UPS
      (e.g., the E3 ubiquitin ligases) can lead to an increase in protein levels in a
      more targeted fashion. Alternatively, multiple strategies for inducing protein
      degradation with small-molecule probes are emerging. With the ability to induce
      and inhibit the degradation of targeted proteins, small-molecule modulators of
      the UPS have the potential to significantly expand the druggable portion of the
      proteome beyond traditional targets, such as enzymes and receptors. 

PMID- 24459098
TI  - High temperature slows down growth in tobacco hornworms (Manduca sexta larvae)
      under food restriction.
AB  - When fed ad libitum (AL), ectothermic animals usually grow faster and have higher
      metabolic rate at higher ambient temperature. However, if food supply is limited,
      there is an energy tradeoff between growth and metabolism. Here we hypothesize
      that for ectothermic animals under food restriction (FR), high temperature will
      lead to a high metabolic rate, but growth will slow down to compensate for the
      high metabolism. We measure the rates of growth and metabolism of 4 cohorts of
      5th instar hornworms (Manduca sexta larvae) reared at 2 levels of food supply (AL
      and FR) and 2 temperatures (20 and 30  degrees C). Our results show that,
      compared to the cohorts reared at 20  degrees C, the ones reared at 30  degrees C
      have high metabolic rates under both AL and FR conditions, but a high growth rate
      under AL and a low growth rate under FR, supporting this hypothesis. 

PMID- 24459099
TI  - Comparison of 10 brain tissue segmentation methods using revisited IBSR
      annotations.
AB  - PURPOSE: Ground-truth annotations from the well-known Internet Brain Segmentation
      Repository (IBSR) datasets consider Sulcal cerebrospinal fluid (SCSF) voxels as
      gray matter. This can lead to bias when evaluating the performance of tissue
      segmentation methods. In this work we compare the accuracy of 10 brain tissue
      segmentation methods analyzing the effects of SCSF ground-truth voxels on
      accuracy estimations. MATERIALS AND METHODS: The set of methods is composed by
      FAST, SPM5, SPM8, GAMIXTURE, ANN, FCM, KNN, SVPASEG, FANTASM, and PVC. Methods
      are evaluated using original IBSR ground-truth and ranked by means of their
      performance on pairwise comparisons using permutation tests. Afterward, the
      evaluation is repeated using IBSR ground-truth without considering SCSF. RESULTS:
      The Dice coefficient of all methods is affected by changes in SCSF annotations,
      especially on SPM5, SPM8 and FAST. When not considering SCSF voxels, SVPASEG
      (0.90 +/- 0.01) and SPM8 (0.91 +/- 0.01) are the methods from our study that
      appear more suitable for gray matter tissue segmentation, while FAST (0.89 +/-
      0.02) is the best tool for segmenting white matter tissue. CONCLUSION: The
      performance and the accuracy of methods on IBSR images vary notably when not
      considering SCSF voxels. The fact that three of the most common methods (FAST,
      SPM5, and SPM8) report an important change in their accuracy suggest to consider
      these differences in labeling for new comparative studies.

PMID- 24459100
TI  - Binary Pd-polyoxometalates and isolation of a ternary Pd-V-polyoxomolybdate
      active species for selective aerobic oxidation of alcohols.
AB  - Binary Pd-polyoxometalates [Pd(dpa)2]3 [PW12 O40]2 ?12 DMSO (2), [Pd(dpa)2]3
      [PMo12 O40]2 ?12 DMSO?2 H2 O (3), and [Pd(dpa)(DMSO)2]2 [HPMo10 V2 O40 ]?4 DMSO
      (4) were synthesized by reaction of [Pd(dpa)(OAc)2]?2 H2 O (1; dpa=2,2'
      dipyridylamine) with three Keggin-type polyoxometalates and fully characterized
      by single-crystal and powder XRD analyses, IR spectroscopy, and elemental
      analyses. The synthesis is facile and straightforward, and the complicated ligand
      modification procedure often used in the traditional charge-transfer method can
      be omitted. In 2-4, Pd complexes and polyoxometalate anions are coupled through
      electrostatic interaction. Compound 4 is more active than the other three
      compounds in the selective aerobic oxidation of alcohols at ambient pressure.
      Interestingly, during catalytic recycling of compound 4, unprecedented ternary Pd
      V-polyoxometalate [Pd(dpa)2 {VO(DMSO)5}2][PMo12 O40]2 ?4 DMSO (5), which was
      captured and characterized by single-crystal XRD, proved to be the true active
      species and showed high catalytic activity for the selective aerobic oxidation of
      aromatic alcohols (98.1-99.8 % conversion, 91.5-99.1 % selectivity). Moreover, on
      the basis of control experiments and EPR and UV/Vis spectra, a plausible reaction
      mechanism for the oxidation of alcohols catalyzed by 5 was proposed.

PMID- 24459101
TI  - 'Being a presence': The ways in which family support workers encompass, embrace,
      befriend, accompany and endure with families of life-limited children.
AB  - Children with life-limiting and disabling conditions are surviving longer than
      previously, and many require palliative and supportive care, usually at home.
      Home-based care can put family life under considerable strain, as parents care
      for their child's complex, often unpredictable, continuing care needs. Rainbow
      Trust Children's Charity aims to bridge gaps in services for children with life
      threatening or terminal conditions by providing family support workers (FSWs).
      The study used a range of methods (surveys, interviews and ethnographic
      observation) approach to explore key aspects of the work of the FSWs. The target
      population for the surveys was families with a child having complex, life
      threatening or terminal conditions receiving care from FSWs. The participants
      included 55 families (12 bereaved) and 39 children aged 2-18 years. Thematic
      analysis revealed how the FSWs became a presence in families' lives in three main
      ways: (1) encompassing and embracing families through supporting needs and
      promoting resilience; (2) befriending and bonding through developing knowledge,
      trusting relationships and a sense of closeness; and (3) accompanying and
      enduring by 'being with' families in different settings, situations and crises
      and by enduring alongside the families. The study demonstrated the fundamental
      importance of workers who are able to provide aspects of support that is usually
      not provided by other services. 

PMID- 24459102
TI  - Parental attitudes to children's pain and analgesic drugs in the United Kingdom.
AB  - Many children experience treatable moderate to severe pain following surgery.
      Increasingly, children undergo surgery as day cases, and, as such, parents are
      more likely to be responsible for managing pain post-operatively. Research in the
      United States and Finland has found parents fear the side effects of analgesics;
      think they are addictive; and that children should receive as little analgesia as
      possible. Little is known about parental attitudes in this context in the United
      Kingdom. This study set out to explore parental attitudes towards children's pain
      and analgesic drugs to contribute to existing knowledge about parental attitudes
      elsewhere so that the information provided to parents can be tailored
      effectively. A convenience sample of parents (n = 108) at one hospital in South
      West London completed the Parental Pain Expression Perceptions and the Medication
      Attitudes Questionnaires. Although many parents have a good understanding of the
      ways in which children express pain, a substantial proportion of parents hold
      misconceptions regarding how children express pain and concerns in relation to
      analgesic drugs. This may impact on the quality of the pain management provided
      to children post-operatively and needs taking into account when preparing parents
      in this context. 

PMID- 24459103
TI  - Test-strip-based fluorometric detection of fluoride in aqueous media with a
      BODIPY-linked hydrogen-bonding receptor.
AB  - The measurement of biologically relevant anions, such as fluoride, is an
      important task in analytical chemistry, in particular, for dental health and
      osteoporosis. Although a large number of fluoride probes are known, the
      applicability under relevant conditions is limited to a few examples. To improve
      this situation, BODIPY-amidothiourea dyes with varying hydrogen-bond donating
      strengths were developed, the most H-acidic of which (1 c) could detect F(-) from
      an inorganic source (NaF) in 50 % aqueous solution (DMSO/water 1:1, v/v) with
      0.01 ppm sensitivity through selective fluorescence quenching by a photoinduced
      electron-transfer (PET) process. Use of the probe and a reference dye with a test
      strip assay and a portable and rapidly recording lateral-flow fluorescence reader
      made determination of F(-) in neat aqueous solutions, such as spiked water
      samples and toothpaste extracts, possible in a self-referenced manner, achieving
      a detection limit of 0.2 ppm. 

PMID- 24459104
TI  - From bare to covered: 15-year single center experience and follow-up in trans
      catheter stent implantation for aortic coarctation.
AB  - BACKGROUND: Bare stents has become the first line therapy for aortic coarctation.
      Covered stents has been reported more recently in clinical practice. OBJECTIVES:
      The present study, reports comparatively 15-year experience of bare and covered
      stent implantation for aortic coarctation in a single tertiary referral center.
      METHODS: From 1997 to 2011, 143 patients with native or postoperative aortic
      coarctation were treated at our institution. Seventy-one subjects (median age 17
      years (range from 4 to 70 years) underwent bare stent implantation (Group 1)
      while 72 patients (median age of 17.5 years (range from 6 to 68 years) underwent
      covered stent implantation (Group 2). RESULTS: Success rate in the whole group
      was 95%. More complex and tighter coarctations were treated using covered stents.
      Incidence of related-procedure adverse events was higher in Group 1 than in group
      2 (21.1% vs. 8.3% P = 0.035). Aortic wall complications occurred in 7% of
      patients in Group 1 (one death) and 0% in Group 2 (P = 0.028). Subjects in Group
      1 had a longer follow-up (median 85 vs. 35 months; P < 0.001). Independent
      predictors associated with reintervention included the presence of complex
      lesions (HR: 2.70; CI: 1.15-6.32), balloon diameter used <14 mm (HR: 3.76; CI:
      1.48-9.55), and immediate residual gradient >10 mm Hg (HR: 4.30; CI: 1.96-9.47).
      CONCLUSIONS: Both bare and covered stent implantation for aortic coarctation is a
      safe and efficacious treatment. By using covered stent implantation the spectrum
      of patients treated has increased with lower rates of acute and late
      complications.

PMID- 24459105
TI  - Brain. Editorial.

PMID- 24459106
TI  - Sensory neuropathy with bone destruction due to a mutation in the membrane
      shaping atlastin GTPase 3.
AB  - Many neurodegenerative disorders present with sensory loss. In the group of
      hereditary sensory and autonomic neuropathies loss of nociception is one of the
      disease hallmarks. To determine underlying factors of sensory neurodegeneration
      we performed whole-exome sequencing in affected individuals with the disorder. In
      a family with sensory neuropathy with loss of pain perception and destruction of
      the pedal skeleton we report a missense mutation in a highly conserved amino acid
      residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The
      same mutation (p.Tyr192Cys) was identified in a second family with similar
      clinical outcome by screening a large cohort of 115 patients with hereditary
      sensory and autonomic neuropathies. Both families show an autosomal dominant
      pattern of inheritance and the mutation segregates with complete penetrance. ATL3
      is a paralogue of ATL1, a membrane curvature-generating molecule that is involved
      in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are
      enriched in three-way junctions, branch points of the endoplasmic reticulum that
      connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails
      to localize to branch points, but instead disrupts the structure of the tubular
      endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative
      effect. Identification of ATL3 as novel disease-associated gene exemplifies that
      long-term sensory neuronal maintenance critically depends on the structural
      organisation of the endoplasmic reticulum. It emphasizes that alterations in
      membrane shaping-proteins are one of the major emerging pathways in axonal
      degeneration and suggests that this group of molecules should be considered in
      neuroprotective strategies. 

PMID- 24459110
TI  - Understanding principles of miRNA target recognition and function through
      integrated biological and bioinformatics approaches.
AB  - In recent times, microRNA (miRNA) have emerged as primary regulators of
      fundamental biological processes including cellular differentiation,
      proliferation, apoptosis, as well as synaptic plasticity. However, miRNAs bind
      their targets with only partial complementarity, making it very challenging to
      determine exactly how a miRNA is functioning in specific biological environments.
      This review discusses key principles of miRNA target recognition and function
      which have emerged through the progressive advancement of biological and
      bioinformatics approaches. Ultimately, the integration of gene expression and
      biochemical methods with sequence- and systems-based bioinformatics approaches
      will reveal profound insights regarding the importance of target contextual
      features in determining miRNA target recognition and regulatory outcome, as well
      as the importance of RNA interaction networks in enabling miRNA to regulate
      different target genes and functions in specific biological contexts. There is
      therefore a demand for the elegant design of future experiments such that
      principles of context-specific miRNA target recognition and regulatory outcome
      can be accurately modeled in normal developmental and disease states.

PMID- 24459107
TI  - HTT-lowering reverses Huntington's disease immune dysfunction caused by NFkappaB
      pathway dysregulation.
AB  - Huntington's disease is an inherited neurodegenerative disorder caused by a CAG
      repeat expansion in the huntingtin gene. The peripheral innate immune system
      contributes to Huntington's disease pathogenesis and has been targeted
      successfully to modulate disease progression, but mechanistic understanding
      relating this to mutant huntingtin expression in immune cells has been lacking.
      Here we demonstrate that human Huntington's disease myeloid cells produce
      excessive inflammatory cytokines as a result of the cell-intrinsic effects of
      mutant huntingtin expression. A direct effect of mutant huntingtin on the
      NFkappaB pathway, whereby it interacts with IKKgamma, leads to increased
      degradation of IkappaB and subsequent nuclear translocation of RelA.
      Transcriptional alterations in intracellular immune signalling pathways are also
      observed. Using a novel method of small interfering RNA delivery to lower
      huntingtin expression, we show reversal of disease-associated alterations in
      cellular function-the first time this has been demonstrated in primary human
      cells. Glucan-encapsulated small interfering RNA particles were used to lower
      huntingtin levels in human Huntington's disease monocytes/macrophages, resulting
      in a reversal of huntingtin-induced elevated cytokine production and
      transcriptional changes. These findings improve our understanding of the role of
      innate immunity in neurodegeneration, introduce glucan-encapsulated small
      interfering RNA particles as tool for studying cellular pathogenesis ex vivo in
      human cells and raise the prospect of immune cell-directed HTT-lowering as a
      therapeutic in Huntington's disease. 

PMID- 24459111
TI  - Methodological aspects of an off-line combination of preparative isotachophoresis
      and high-performance liquid chromatography with mass spectrometry in the analysis
      of biological matrices.
AB  - This work reports on some methodological aspects of an off-line combination of
      preparative ITP and HPLC with mass spectrometric detection (pITP-HPLC-MS) and its
      potential applications to the analysis of high molecular mass compounds present
      in complex biological matrices from the analytical chemistry perspective.
      Lysozyme served as the model analyte and human saliva as the complex biological
      matrix in this study. A mixture of five low-molecular mass compounds was found
      and successfully used in the pITP experiments as discrete spacers to isolate the
      analyte from the interferents present in the complex biological matrix and to
      minimize their disturbance effect on the final MS analysis. The experiments at
      the pITP stage were performed in the cationic mode. On-column conductivity
      detectors were used for the detection of ITP zones. Lysozyme was found in the
      human saliva samples using just deconvolution of the MS data after background
      correction. The MS data obtained from HPLC-MS analysis of pITP fractions
      exhibited the great analytical potential of the combination of pITP-HPLC-MS
      resulting from the ITP clean-up effect as well as the ITP preconcentration of the
      analyte present at low concentration levels in complex biological matrices.

PMID- 24459112
TI  - Enantioselective continuous-flow production of 3-indolylmethanamines mediated by
      an immobilized phosphoric acid catalyst.
AB  - A polystyrene-supported 1,1'-bi-2-naphthol derived phosphoric acid has been
      synthesized and applied in the enantioselective Friedel-Crafts reaction of
      indoles and sulfonylimines. The immobilized catalyst was highly active and
      selective, and gave rise to a broad range of 3-indolylmethanamines (19 examples)
      in high yields and excellent enantioselectivities (up to 98 % enantiomeric
      excess) after short reaction times under very convenient reaction conditions (RT
      in dichloromethane). Moreover, repeated recycling (14 cycles) was possible with
      no substantial loss in catalytic performance and the system could be adapted to a
      continuous-flow operation (6 h). Finally, the applicability of the system was
      further confirmed by rapid access to a library of compounds with three points of
      diversity in a single continuous-flow experiment that involved sequential pumping
      of different substrate combinations. 

PMID- 24459113
TI  - Comparative effectiveness of monotherapy with mood stabilizers versus second
      generation (atypical) antipsychotics for the treatment of bipolar disorder in
      children and adolescents.
AB  - OBJECTIVE: This study compared the effectiveness and safety of second generation
      (atypical) antipsychotic (SGA) versus traditional mood stabilizers (MS) in
      children and adolescents with bipolar disorder. METHODS: The study was a
      retrospective cohort study on 5 years (2003-2007) of Medicaid claims data from
      four geographically diversified states. Children and adolescents aged 6-18 years
      who initiated a new treatment episode for bipolar disorder on either an SGA or an
      MS were followed for 12 months to compare the effectiveness and safety between
      the two therapeutic categories for pediatric bipolar disorder (PBD). The outcome
      measures were psychiatric hospital admission, all cause medication
      discontinuation and treatment augmentation. Potential selection bias caused by
      unobserved confounding was addressed with instrumental variable methods, using
      physician prescribing preference and year of cohort entry as the instruments.
      Sensitivity analysis was conducted to test the robustness of findings against the
      uncertainties on PBD diagnosis. RESULTS: Of the 7423 bipolar children and
      adolescents identified, 66.60% started treatment on SGA, whereas 33.40% initiated
      on MS. Patients who initiated on MS and SGA had comparable risk of psychiatric
      hospital admission (HR=1.172, 95%CI: 0.827-1.660). However, as compared with
      those who initiated on MS, patients who initiated on SGA were less likely to
      discontinue the treatment (HR=0.634, 95%CI: 0.419-0.961) and less likely to
      receive treatment augmentation (HR=0.223, 95%CI: 0.103-0.484). CONCLUSION: As
      compared with MS monotherapy, SGA monotherapy could be a more effective and safer
      treatment option for PBD.

PMID- 24459114
TI  - Incidence of acute kidney injury following cardiac catheterization prior to
      cardiopulmonary bypass in children.
AB  - OBJECTIVES: To determine whether contrast administration was a risk factor for
      development of acute kidney injury (AKI) in cyanotic congenital heart disease
      (CHD) patients undergoing cardiopulmonary bypass (CPB). BACKGROUND: AKI following
      CPB or contrast administration is well described. In previous studies,
      administration of contrast prior to CPB has been shown to increase the risk of
      AKI. Chronic cyanosis leads to glomerular damage and dysfunction, thus
      potentially placing this population at increased risk of developing AKI following
      contrast administration prior to CPB. METHODS: One hundred twenty-two patients
      with cyanotic CHD undergoing preoperative cardiac catheterization (PCC) and
      subsequent CPB at Children's Medical Center of Dallas from January 1, 2007 until
      November 30, 2010 were identified, looking specifically at bi-directional Glenn
      (BDG) anastomoses and Fontan procedures. One hundred thirteen patients undergoing
      PCC <= 48 hr prior to and > 5 days prior to CPB were included. Occurrence of AKI
      following CPB was the primary outcome variable. RESULTS: Logistic regression
      analysis revealed pre-catheterization serum creatinine was a risk factor for post
      CPB AKI (P < 0.001) in both Fontan and BDG patients. All other variables were not
      significantly associated with the development of AKI in either BDG or Fontan
      patients. Length of stay (hospital or ICU) was not different among the groups
      regardless of the occurrence of AKI. CONCLUSIONS: In this study of cyanotic CHD
      patients, contrast administration within 48 hr prior to CPB was not an additional
      risk factor for the development of AKI.

PMID- 24459115
TI  - Exploring the mechanism how Marburg virus VP35 recognizes and binds dsRNA by
      molecular dynamics simulations and free energy calculations.
AB  - Filoviruses often cause terrible infectious disease which has not been
      successfully dealt with pharmacologically. All filoviruses encode a unique
      protein termed VP35 which can mask doubled-stranded RNA to deactivate interferon.
      The interface of VP35-dsRNA would be a feasible target for structure-based
      antiviral agent design. To explore the essence of VP35-dsRNA interaction,
      molecular dynamics simulation combined with MM-GBSA calculations were performed
      on Marburg virus VP35-dsRNA complex and several mutational complexes. The
      energetic analysis indicates that nonpolar interactions provide the main driving
      force for the binding process. Although the intermolecular electrostatic
      interactions play important roles in VP35-dsRNA interaction, the whole polar
      interactions are unfavorable for binding which result in a low binding affinity.
      Compared with wild type VP35, the studied mutants F228A, R271A, and K298A have
      obviously reduced binding free energies with dsRNA reflecting in the reduction of
      polar or nonpolar interactions. The results also indicate that the loss of
      binding affinity for one dsRNA strand would abolish the total binding affinity.
      Three important residues Arg271, Arg294, and Lys298 which makes the largest
      contribution for binding in VP35 lose their binding affinity significantly in
      mutants. The uncovering of VP35-dsRNA recognition mechanism will provide some
      insights for development of antiviral drug.

PMID- 24459116
TI  - Chemoselective and direct functionalization of methyl benzyl ethers and
      unsymmetrical dibenzyl ethers by using iron trichloride.
AB  - Methyl and benzyl ethers are widely utilized as protected alcohols due to their
      chemical stability, such as the low reactivity of the methoxy and benzyloxy
      groups as leaving groups under nucleophilic conditions. We have established the
      direct azidation of chemically stable methyl and benzyl ethers derived from
      secondary and tertiary benzyl alcohols. The present azidation chemoselectively
      proceeds at the secondary or tertiary benzylic positions of methyl benzyl ethers
      or unsymmetrical dibenzyl ethers and is also applicable to direct allylation,
      alkynylation, and cyanation reactions, as well as the azidation. The present
      methodologies provide not only a novel chemoselectivity but also the advantage of
      shortened synthetic steps, due to the direct process without the deprotection of
      the methyl and benzyl ethers. 

PMID- 24459117
TI  - Effect of external electrostatic field on the stability of beta sheet structures.
AB  - To explore the effect of an external electrostatic field (EEF) on the stability
      of protein conformations, the molecular dynamic modeling approach was applied to
      evaluate the effect of an EEF along the x or y direction on a water cluster
      containing a parallel or antiparallel beta sheet structure. The beta sheet
      structure contained two strands with a (Gly)3 sequence separated by a distance d
      along the x direction. The mean forces between the two strands along the x
      direction were computed from the trajectories of molecular dynamics simulations.
      In the absence of the EEF, the forces between the two strands in vacuum were
      repulsive and attractive in the parallel and antiparallel beta sheet structures,
      respectively. In contrast, the mean forces between the two strands in water were
      attractive in both the parallel and antiparallel beta sheet structures. This is
      because the electric interactions between the two strands were shielded by water,
      and the hydrophobic effect dominated the interaction between the two strands.
      When an EEF >50 MV/cm was applied to the water cluster, the attractive force
      between the two strands in the parallel and antiparallel beta sheet structures
      decreased and increased, respectively. Further, the binding affinity between the
      two strands in the parallel and antiparallel beta sheet structures also decreased
      and increased, respectively. This is because the large EEF leads to dielectric
      saturation, and consequently reduces the effects of the dielectric shielding and
      hydrophobic interactions.

PMID- 24459118
TI  - Some health effects of aircraft noise with special reference to shift work.
AB  - BACKGROUND: Aircraft noise is an environmental stressor. A positive relationship
      exists between noise and high blood pressure. Shift work is an additional
      hazardous working condition with negative effect on the behavior attitude of
      workers. OBJECTIVE: This study aimed at investigating some health hazards for
      shift work on workers at Cairo International Airport (CIA), Egypt, as a strategic
      work place, with more than one stressor. SUBJECTS AND METHODS: Assessment of
      noise effects were carried out in four working sites at the airport besides
      control sites. The average noise level in the exposure sites was 106.5 dB
      compared with 54 dB at the control sites. The study comprised a group of 200 male
      workers exposed to aircraft noise and 110 male workers not exposed to noise as
      control group. All workers had full general medical examination after filling
      specially formulated questionnaire. Hearing impairment, raised blood pressure,
      headaches, disturbed sleep, and symptoms of anxiety were more prominent among the
      exposed workers than the control. Symptoms of upper respiratory tract were
      reported among night shifters of both groups with high tendency for smoking.
      Thus, night-shift workers at CIA work under more than one stressor. Hypertension
      and smoking might act as intermediate factors on the causal pathway of
      complaints, making aircraft noise and night shift acting as two synergistic
      stressors. Airport workers are in need for aggressive hearing conservation
      programs. Organization of the working hours schedule is mandatory to avoid
      excessive noise exposure.

PMID- 24459119
TI  - Nurse scientists' information literacy is supported by librarians.

PMID- 24459121
TI  - Interannual variation and host affiliations of endophytic fungi associated with
      ferns at La Selva, Costa Rica.
AB  - Ferns are an ancient and diverse lineage of vascular plants that differ
      morphologically, chemically and in growth habits from the angiosperms with which
      they co-occur. We used a culture-based approach coupled with phylogenetic
      analyses to characterize the incidence, diversity and composition of fungal
      endophyte assemblages in ferns, with a focus on healthy aboveground tissues of
      seven species of eupolypods at La Selva, Costa Rica. Endophytes were isolated
      from every individual plant and were similarly abundant and diverse in frond
      blades and stalks, in different vegetation types, in epiphytic vs. terrestrial
      species, and between sampling years. However, abundance, diversity and community
      structure differed significantly among fern species, and composition differed
      markedly between sampling years. Phylogenetic classification using separate and
      combined datasets revealed that as for many Neotropical angiosperms, the majority
      (95%) of endophyte taxa were Ascomycota, with particular dominance by
      Sordariomycetes, Eurotiomycetes and Dothideomycetes. However, our data suggest
      higher phylogenetic richness and stronger host affinities in fern associated
      endophytes relative to those studied in angiosperms thus far. 

PMID- 24459125
TI  - Nomenclatural realignment of Neotyphodium species with genus Epichole.
AB  - Nomenclatural rule changes in the International Code of Nomenclature for algae,
      fungi and plants, adopted at the 18th International Botanical Congress in
      Melbourne, Australia, in 2011, provide for a single name to be used for each
      fungal species. The anamorphs of Epichloe species have been classified in genus
      Neotyphodium, the form genus that also includes most asexual Epichloe
      descendants. A nomenclatural realignment of this monophyletic group into one
      genus would enhance a broader understanding of the relationships and common
      features of these grass endophytes. Based on the principle of priority of
      publication we propose to classify all members of this clade in the genus
      Epichloe. We have reexamined classification of several described Epichloe and
      Neotyphodium species and varieties and propose new combinations and states. In
      this treatment we have accepted 43 unique taxa in Epichloe, including distinct
      species, subspecies, and varieties. We exclude from Epichloe the two taxa
      Neotyphodium starrii, as nomen dubium, and Neotyphodium chilense, as an unrelated
      taxon.

PMID- 24459128
TI  - Surviving colonization and the quest for healing: narrative and resilience among
      California Indian tribal leaders.
AB  - American Indians must negotiate the cultural and psychological legacy of
      colonialism as they construct coherent, purposive individual and communal
      narratives. Analysis of the life stories of highly generative members of these
      groups who have emerged as leaders offers important insights for psychological
      adaptation in the context of the historical legacy of colonialism. Based on an
      interpretive analysis of the life stories of two California Indian tribal
      leaders, we posit a resilient-strength-based approach to narrative identity
      development to complement and counter the historical trauma discourse. Native
      American identity emerged as the major source of psychological resilience in the
      life stories analyzed. This identity manifested and was supported through a
      commitment to the wellness of tribal community, spiritual practices, and beliefs.
      For these men, their relationship to their grandmothers was central in molding
      their identities and serving as a source of resilience throughout their lives. As
      leaders of a federally unrecognized tribal group, they have adopted a narrative
      of survivance (Vizenor, 2008), which appears to buffer psychosocial stress and
      provide a resilient narrative identity. Based on these findings, we theorize an
      indigenous California Native psychology of resilience. 

PMID- 24459129
TI  - Application of dual Willis covered stents in the management of large fusiform
      carotid aneurysms in a canine model.
AB  - This study evaluates the efficacy of dual Willis covered stents for the treatment
      of large fusiform carotid aneurysms in a canine model. Carotid fusiform aneurysms
      >10 mm long were surgically created in 10 dogs and were then repaired using
      either single or dual covered stents. Clinical results were assessed by scheduled
      angiography and histological features by light and electron microscopy.
      Angiography immediately post-op and 6 months after surgery revealed aneurysm
      isolation rates of 60 and 20% for the single stent technique and 60 and 100% for
      the dual stent technique, respectively. The rate of complete obliteration of the
      aneurysm sac differed significantly between treatments (P = 0.048). The dual
      stent technique also resulted in greater endothelialization. For large carotid
      fusiform aneurysms in a canine model, endovascular repair using dual Willis
      covered stents is technically feasible and more effectively obliterates the
      aneurysm sac than the use of a single stent.

PMID- 24459130
TI  - Epidemiology of concomitant injuries in traumatic thoracic aortic rupture: a meta
      analysis.
AB  - Traumatic thoracic aortic rupture is a highly lethal injury. For those who arrive
      alive at the hospital, it is of utmost importance to quickly evaluate concomitant
      injuries and prioritize therapeutic interventions. We aimed to review the
      frequency of concomitant injuries in patients with thoracic aortic rupture,
      according to anatomic location and type of injury. A systematic literature search
      of six medical databases led to the identification of 90 publications; 27
      categories of thoracic aortic rupture concomitant injuries were thereafter
      created. The respective pooled proportions and 95% confidence intervals were
      calculated and ranked in order of frequency. Among the 7258 patients studied,
      orthopedic fractures were the most frequent thoracic aortic rupture concomitant
      injury, amounting to a high pooled proportion of almost 70%, followed by thoracic
      injury in ~50% and abdominal injury in over 40%. Pooled proportion for any type
      of head injury was also high (37%) pointing to the multiple-injury type of
      lesions among thoracic aortic rupture victims. Thoracic aortic rupture is a
      devastating injury, but rarely occurs as a sole traumatic entity. The recognition
      of concomitant thoracic, abdominal, head injuries and fractures after thoracic
      aortic rupture is of paramount importance. Future studies should focus on the
      impact of these injuries upon survival, morbidity and disability of multiple
      injured thoracic aortic rupture patients. 

PMID- 24459131
TI  - Is the temperature of tumescent anesthesia applied in the endovenous laser
      ablation important? comparison of different temperatures for tumescent anesthesia
      applied during endovenous ablation of incompetent great saphenous vein with a
      1470 nm diode laser.
AB  - INTRODUCTION: We aimed to investigate whether the temperature of tumescent
      anesthesia is important, if so, to establish an opinion about the ideal
      temperature. MATERIALS AND METHODS: Endovenous laser ablations were performed in
      72 patients; 35 patients (Group A) received tumescent anesthesia at +4C, while
      other 37 patients (Group B) received tumescent anesthesia at room temperature.
      The groups were compared in terms of intraoperative pain, postoperative regional
      pain, ecchymosis, paresthesia, skin burns and necrosis. At month 1, great
      saphenous vein was evaluated for recanalization and patient satisfaction.
      RESULTS: The survey on intraoperative pain showed that patients receiving
      tumescent anesthesia at +4C experienced much less pain. Interestingly,
      statistical analysis showed that this difference was not significant (p = 0.072).
      No skin burns or necrosis occurred in either group, whereas ecchymosis and
      paresthesia were the most frequently observed side effects in both groups, but no
      significant difference was found between the groups. There was no significant
      difference between pain levels on postoperative days and no significant
      difference between the groups in terms of satisfaction with endovenous laser
      ablation procedure and postoperative satisfaction. All venous segments treated
      with endovenous laser ablation in both groups were occluded. At month 1 no
      recanalization was observed. CONCLUSION: We conclude that the temperature of
      tumescent anesthesia solution is not important, while the proper administration
      of tumescent solution in adequate amounts ensuring delivery of the fluid to all
      segments appears to be a more significant determinant for the success of the
      procedure.

PMID- 24459132
TI  - Chromosome positioning from activity-based segregation.
AB  - Chromosomes within eukaryotic cell nuclei at interphase are not positioned at
      random, since gene-rich chromosomes are predominantly found towards the interior
      of the cell nucleus across a number of cell types. The physical mechanisms that
      could drive and maintain the spatial segregation of chromosomes based on gene
      density are unknown. Here, we identify a mechanism for such segregation, showing
      that the territorial organization of chromosomes, another central feature of
      nuclear organization, emerges naturally from our model. Our computer simulations
      indicate that gene density-dependent radial segregation of chromosomes arises as
      a robust consequence of differences in non-equilibrium activity across
      chromosomes. Arguing that such differences originate in the inhomogeneous
      distribution of ATP-dependent chromatin remodeling and transcription machinery on
      each chromosome, we show that a variety of non-random positional distributions
      emerge through the interplay of such activity, nuclear shape and specific
      interactions of chromosomes with the nuclear envelope. Results from our model are
      in reasonable agreement with experimental data and we make a number of
      predictions that can be tested in experiments. 

PMID- 24459133
TI  - Folding a stable RNA pseudoknot through rearrangement of two hairpin structures.
AB  - Folding messenger RNA into specific structures is a common regulatory mechanism
      involved in translation. In Escherichia coli, the operator of the rpsO gene
      transcript folds into a pseudoknot or double-hairpin conformation. S15, the gene
      product, binds only to the pseudoknot, thereby repressing its own synthesis when
      it is present in excess in the cell. The two RNA conformations have been proposed
      to exist in equilibrium. However, it remained unclear how structural changes can
      be achieved between these two topologically distinct conformations. We used
      optical tweezers to study the structural dynamics and rearrangements of the rpsO
      operator RNA at the single-molecule level. We discovered that the two RNA
      structures can be interchanged spontaneously and the pseudoknot can exist in
      conformations that exhibit various levels of stability. Conversion from the
      double hairpin to a pseudoknot through potential hairpin-hairpin interactions
      favoured the high-stability conformation. By contrast, mutations that blocked the
      formation of a hairpin typically resulted in alternative low-stability
      pseudoknots. These results demonstrate that specific tertiary interactions of RNA
      can be established and modulated based on the interactions and rearrangements
      between secondary structural components. Our findings provide new insight into
      the RNA folding pathway that leads to a regulatory conformation for target
      protein binding. 

PMID- 24459134
TI  - Suppression of intragenic transcription requires the MOT1 and NC2 regulators of
      TATA-binding protein.
AB  - Chromatin structure in transcribed regions poses a barrier for intragenic
      transcription. In a comprehensive study of the yeast chromatin remodelers and the
      Mot1p-NC2 regulators of TATA-binding protein (TBP), we detected synthetic genetic
      interactions indicative of suppression of intragenic transcription. Conditional
      depletion of Mot1p or NC2 in absence of the ISW1 remodeler, but not in the
      absence of other chromatin remodelers, activated the cryptic FLO8 promoter.
      Likewise, conditional depletion of Mot1p or NC2 in deletion backgrounds of the
      H3K36 methyltransferase Set2p or the Asf1p-Rtt106p histone H3-H4 chaperones,
      important factors involved in maintaining a repressive chromatin environment,
      resulted in increased intragenic FLO8 transcripts. Activity of the cryptic FLO8
      promoter is associated with reduced H3 levels, increased TBP binding and tri
      methylation of H3K4 and is independent of Spt-Ada-Gcn5-acetyltransferase
      function. These data reveal cooperation of negative regulation of TBP with
      specific chromatin regulators to inhibit intragenic transcription. 

PMID- 24459135
TI  - Androgen receptor uses relaxed response element stringency for selective
      chromatin binding and transcriptional regulation in vivo.
AB  - The DNA-binding domains (DBDs) of class I steroid receptors-androgen,
      glucocorticoid, progesterone and mineralocorticoid receptors-recognize a similar
      cis-element, an inverted repeat of 5'-AGAACA-3' with a 3-nt spacer. However,
      these receptors regulate transcription programs that are largely receptor
      specific. To address the role of the DBD in and of itself in ensuring specificity
      of androgen receptor (AR) binding to chromatin in vivo, we used SPARKI knock-in
      mice whose AR DBD has the second zinc finger replaced by that of the
      glucocorticoid receptor. Comparison of AR-binding events in epididymides and
      prostates of wild-type (wt) and SPARKI mice revealed that AR achieves selective
      chromatin binding through a less stringent sequence requirement for the 3'
      hexamer. In particular, a T at position 12 in the second hexamer is dispensable
      for wt AR but mandatory for SPARKI AR binding, and only a G at position 11 is
      highly conserved among wt AR-preferred response elements. Genome-wide AR-binding
      events agree with the respective transcriptome profiles, in that attenuated AR
      binding in SPARKI mouse epididymis correlates with blunted androgen response in
      vivo. Collectively, AR-selective actions in vivo rely on relaxed rather than
      increased stringency of cis-elements on chromatin. These elements are, in turn,
      poorly recognized by other class I steroid receptors. 

PMID- 24459136
TI  - Defective metabolism in polycystic kidney disease: potential for therapy and open
      questions.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder
      characterized by bilateral renal cyst formation. The disease is caused by
      mutations in either the PKD1 or the PKD2 gene. Progress has been made in
      understanding the molecular basis of the disease leading to the general agreement
      on ADPKD being a loss-of-function disease. Identification of signalling cascades
      dysfunctional in the cystic epithelia has led to several pre-clinical studies of
      animal models using a variety of inhibitors to slow disease progression. These
      were followed by clinical trials, some of which generated promising results,
      although an approved therapy is still lacking. Here, we summarize and discuss
      recent work providing evidence that metabolic alterations can be observed in
      ADPKD. In particular, we will focus our discussion on the potential role of
      glucose metabolism in the pathogenesis of ADPKD. These recent findings provide a
      new perspective for the understanding of the pathobiology of ADPKD and open
      potential new avenues for therapeutical approaches. At the same time, these
      studies also raise important and intriguing biological and medical questions that
      will need to be addressed experimentally prior to embracing a more enthusiastic
      view of the applicability of the results. 

PMID- 24459138
TI  - Haemodialysis in patients treated with oral anticoagulant: should we heparinize?
AB  - BACKGROUND: Anticoagulation for the haemodialysis circuit in patients treated
      with oral anticoagulation poses additional haemorrhagic risk. The few available
      data suggest that tapering or even stopping heparinization is feasible and the
      HeprAN membrane with grafted heparin was developed to decrease heparin dose. The
      objective of our study was to evaluate the need for additional anticoagulation in
      patients on long-term oral anticoagulation, according to the type of membrane
      used. METHODS: This is a prospective, randomized, crossover bifactorial trial in
      haemodialysed patients on oral anticoagulation. Each patient had four
      haemodialysis sessions with two different membranes [HeprAN or polysulphone (PS)]
      and with or without enoxaparin. Clinical coagulation was evaluated by the need
      for premature ending and by a visual score (Janssen scale). Coagulation
      activation markers were also measured: d-dimers, prothrombin fragments 1 + 2,
      thrombin-antithrombin complexes, tissue factor pathway inhibitor and platelet
      factor-4. RESULTS: Ten patients were included (M/F = 4/6, mean age 63 +/- 15
      years). None of the 40 sessions ended prematurely. The clotting scores were
      similar with or without enoxaparin (dialyser: 1.49 +/- 0.19 versus 1.53 +/- 0.17,
      P = 0.97; bubble trap: 0.75 +/- 0.19 versus 0.78 +/- 0.22, P = 0.62) and with the
      polysulphone or the HeprAN membrane (dialyser: 1.54 +/- 0.20 versus 1.47 +/-
      0.16, P = 0.65; bubble trap: 0.74 +/- 0.22 versus 0.79 +/- 0.19, P = 0.58). There
      was no significant difference in coagulation activation markers between dialysis
      modalities; however, dialysis efficacy was significantly greater with the PS
      membrane (1.58 +/- 0.07 versus 1.43 +/- 0.06, P = 0.02). CONCLUSIONS: These
      results suggest that haemodialysis without additional anticoagulation is possible
      in patients with oral anticoagulation. The HeprAN membrane did not provide any
      additional benefit compared with a PS membrane.

PMID- 24459137
TI  - FGF23 protein expression in coronary arteries is associated with impaired kidney
      function.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23) levels are elevated in chronic
      kidney disease (CKD) and elevated values have been associated with both heart
      disease and mortality. Recent studies show that FGF23, a protein synthesized by
      osteocytes, is also present in calcified atherosclerotic plaques and may be
      induced by heart disease. Whether vascular expression of FGF23 is associated with
      progressive CKD, however, remains unknown. Therefore, the relationship between
      kidney function, vascular calcification and FGF23 expression was evaluated in
      patients with heart disease. METHODS: Immunohistochemistry for FGF23 was
      performed in coronary arteries of all patients undergoing heart transplantation
      at UCLA between February 2008 and 2010. Immunohistochemical staining for Klotho,
      DMP1, FGFR1, and FGFR3; calcium deposition; and RNA expression of Klotho and DMP1
      were assessed in a subset of eight samples. RESULTS: FGF23 was detected by
      immunohistochemistry in 56% of the coronary artery specimens. Vascular FGF23
      expression correlated with declining kidney function, as evidenced by reduced
      creatinine clearance. FGFR1 and FGFR3 were detected throughout the vascular
      tissue and in calcified plaques. Calcium deposition, Klotho expression and DMP1
      expression correlated with FGF23 immunoreactivity. CONCLUSIONS: The findings
      suggest that the Klotho-FGF23-FGFR system is active in coronary arteries and its
      upregulation correlates with impaired renal function and matrix calcium
      deposition.

PMID- 24459139
TI  - Autoantibodies in anti-neutrophil cytoplasm antibody-associated vasculitis.

PMID- 24459140
TI  - International collaborators: more than Facebook friends?

PMID- 24459141
TI  - Inhibition of transcription by B cell Leukemia 3 (Bcl-3) protein requires
      interaction with nuclear factor kappaB (NF-kappaB) p50.
AB  - B cell leukemia 3 (Bcl-3) is an essential negative regulator of NF-kappaB during
      Toll-like receptor and TNF receptor signaling. Bcl-3 also interacts with a number
      of transcriptional regulators, including homodimers of the NF-kappaB p50 subunit.
      Deletion of Bcl-3 results in increased NF-kappaB p50 ubiquitination and
      proteasomal degradation and increased inflammatory gene expression. We employed
      immobilized peptide array technology to define a region of p50 required for the
      formation of a Bcl-3.p50 homodimer immunosuppressor complex. Our data demonstrate
      that amino acids 359-361 and 363 of p50 are critical for interaction with Bcl-3
      and essential for Bcl-3-mediated inhibition of inflammatory gene expression. Bcl
      3 is unable to interact with p50 when these amino acids are mutated, rendering it
      incapable of inhibiting the transcriptional activity of NF-kappaB. Bcl-3
      interaction-defective p50 is hyperubiquitinated and has a significantly reduced
      half-life relative to wild-type p50. Nfkb1(-/-) cells reconstituted with mutated
      p50 precursor p105 are hyperresponsive to TNFalpha stimulation relative to wild
      type p105, as measured by inflammatory gene expression. Mutant p105 recapitulates
      a Bcl3(-/-) phenotype. This study demonstrates that interaction with p50 is
      necessary and sufficient for the anti-inflammatory properties of Bcl-3 and
      further highlights the importance of p50 homodimer stability in the control of NF
      kappaB target gene expression. 

PMID- 24459142
TI  - Polycystin-1 negatively regulates Polycystin-2 expression via the
      aggresome/autophagosome pathway.
AB  - Mutations of the PKD1 and PKD2 genes, encoding polycystin-1 (PC1) and polycystin
      2 (PC2), respectively, lead to autosomal dominant polycystic kidney disease.
      Interestingly, up-regulation or down-regulation of PKD1 or PKD2 leads to
      polycystic kidney disease in animal models, but their interrelations are not
      completely understood. We show here that full-length PC1 that interacts with PC2
      via a C-terminal coiled-coil domain regulates PC2 expression in vivo and in vitro
      by down-regulating PC2 expression in a dose-dependent manner. Expression of the
      pathogenic mutant R4227X, which lacks the C-terminal coiled-coil domain, failed
      to down-regulate PC2 expression, suggesting that PC1-PC2 interaction is necessary
      for PC2 regulation. The proteasome and autophagy are two pathways that control
      protein degradation. Proteins that are not degraded by proteasomes precipitate in
      the cytoplasm and are transported via histone deacetylase 6 (HDAC6) toward the
      aggresomes. We found that HDAC6 binds to PC2 and that expression of full-length
      PC1 accelerates the transport of the HDAC6-PC2 complex toward aggresomes, whereas
      expression of the R4227X mutant fails to do so. Aggresomes are engulfed by
      autophagosomes, which then fuse with the lysosome for degradation; this process
      is also known as autophagy. We have now shown that PC1 overexpression leads to
      increased degradation of PC2 via autophagy. Interestingly, PC1 does not activate
      autophagy generally. Thus, we have now uncovered a new pathway suggesting that
      when PC1 is expressed, PC2 that is not bound to PC1 is directed to aggresomes and
      subsequently degraded via autophagy, a control mechanism that may play a role in
      autosomal dominant polycystic kidney disease pathogenesis. 

PMID- 24459143
TI  - Calcium channel alpha2delta1 proteins mediate trigeminal neuropathic pain states
      associated with aberrant excitatory synaptogenesis.
AB  - To investigate a potential mechanism underlying trigeminal nerve injury-induced
      orofacial hypersensitivity, we used a rat model of chronic constriction injury to
      the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel
      alpha2delta1 (Cavalpha2delta1) protein dysregulation in trigeminal ganglia and
      associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord
      (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to
      spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial
      hypersensitivity that correlated with Cavalpha2delta1 up-regulation in trigeminal
      ganglion neurons and Vc/C2. Blocking Cavalpha2delta1 with gabapentin, a ligand
      for the Cavalpha2delta1 proteins, or Cavalpha2delta1 antisense
      oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting
      an important role of Cavalpha2delta1 in orofacial pain processing. Importantly,
      increased Cavalpha2delta1 in Vc/C2 superficial dorsal horn was associated with
      increased excitatory synaptogenesis and increased frequency, but not the
      amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons
      that could be blocked by gabapentin. Thus, CCI-ION-induced Cavalpha2delta1 up
      regulation may contribute to orofacial neuropathic pain states through abnormal
      excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter
      release in Vc/C2. 

PMID- 24459144
TI  - Retinoic acid receptor gamma (Rarg) and nuclear receptor subfamily 5, group A,
      member 2 (Nr5a2) promote conversion of fibroblasts to functional neurons.
AB  - Somatic cells can be reprogrammed to neurons and various other cell types with
      retrovirus or lentivirus. The limitation of this technology is that these genome
      integration viruses may increase the risk of gene mutation and cause insertional
      mutagenesis. We recently found that non-integration adenovirus carrying neuronal
      transcription factors can induce fibroblasts to neurons. However, the conversion
      efficiency by the adenovirus is lower than that of the retrovirus or lentivirus.
      Therefore, it is crucial to identify other factors or chemical compounds to
      obtain neurons with high efficiency. In this study we show that the combination
      of Rarg (retinoic acid receptor gamma) and Nr5a2 (nuclear receptor subfamily 5,
      group A, member 2; also known as Lrh-1 (liver receptor homologue 1)) rapidly
      promote the iN cell maturation within 1 week and greatly facilitate the
      conversion with neuronal purities of ~50% and yields of >130%. They also improve
      neuronal pattern formation, electrophysiological characteristics, and functional
      integration in vivo. Moreover, the chemical compound agonists to Rarg and Nr5a2
      function effectively as well. This approach may be used for the generation and
      application of iN cells in regenerative medicine. 

PMID- 24459145
TI  - A dual role for the histone methyltransferase PR-SET7/SETD8 and histone H4 lysine
      20 monomethylation in the local regulation of RNA polymerase II pausing.
AB  - RNA polymerase II (Pol II) promoter-proximal pausing plays a critical role in
      postinitiation transcriptional regulation at many metazoan genes. We showed
      recently that histone H4 lysine 16 acetylation (H4K16Ac), mediated by the MSL
      complex, facilitates the release of paused Pol II. In contrast, H4 lysine 20
      trimethylation (H4K20me3), mediated by SUV420H2, enforces Pol II pausing by
      inhibiting MSL recruitment. However, how the balance between H4K16Ac and H4K20me3
      is locally regulated remains unclear. Here, we demonstrate that PR-SET7/SETD8,
      which monomethylates histone H4 lysine 20 (H4K20me1), controls both H4K16Ac and
      H4K20me3 and in doing so, regulates Pol II pausing dynamics. We find that PR-SET7
      mediated H4K20me1 is necessary for the recruitment of the MSL complex, subsequent
      H4K16Ac, and release of Pol II into active elongation. Although dispensable for
      SUV420H2 recruitment, PR-SET7-mediated H4K20me1 is required for H4K20me3.
      Although depletion of SUV420H2 is sufficient to deplete H4K20me3 and relieve an
      H4K20me3-induced pause, pausing is maintained in the absence of PR-SET7 despite
      H4K20me3 depletion because of an inability to recruit the MSL complex in the
      absence of H4K20me1. These findings highlight the requirement for PR-SET7 and
      H4K20me1 in establishing both the H4K16Ac and H4K20me3 marks and point to a dual
      role in the local regulation of Pol II pausing. 

PMID- 24459147
TI  - A complex of Cas proteins 5, 6, and 7 is required for the biogenesis and
      stability of clustered regularly interspaced short palindromic repeats (crispr)
      derived rnas (crrnas) in Haloferax volcanii.
AB  - The clustered regularly interspaced short palindromic repeats/CRISPR-associated
      (CRISPR-Cas) system is a prokaryotic defense mechanism against foreign genetic
      elements. A plethora of CRISPR-Cas versions exist, with more than 40 different
      Cas protein families and several different molecular approaches to fight the
      invading DNA. One of the key players in the system is the CRISPR-derived RNA
      (crRNA), which directs the invader-degrading Cas protein complex to the invader.
      The CRISPR-Cas types I and III use the Cas6 protein to generate mature crRNAs.
      Here, we show that the Cas6 protein is necessary for crRNA production but that
      additional Cas proteins that form a CRISPR-associated complex for antiviral
      defense (Cascade)-like complex are needed for crRNA stability in the CRISPR-Cas
      type I-B system in Haloferax volcanii in vivo. Deletion of the cas6 gene results
      in the loss of mature crRNAs and interference. However, cells that have the
      complete cas gene cluster (cas1-8b) removed and are transformed with the cas6
      gene are not able to produce and stably maintain mature crRNAs. crRNA production
      and stability is rescued only if cas5, -6, and -7 are present. Mutational
      analysis of the cas6 gene reveals three amino acids (His-41, Gly-256, and Gly
      258) that are essential for pre-crRNA cleavage, whereas the mutation of two amino
      acids (Ser-115 and Ser-224) leads to an increase of crRNA amounts. This is the
      first systematic in vivo analysis of Cas6 protein variants. In addition, we show
      that the H. volcanii I-B system contains a Cascade-like complex with a Cas7,
      Cas5, and Cas6 core that protects the crRNA. 

PMID- 24459146
TI  - Functional and structural characterization of Vibrio cholerae extracellular
      serine protease B, VesB.
AB  - The chymotrypsin subfamily A of serine proteases consists primarily of eukaryotic
      proteases, including only a few proteases of bacterial origin. VesB, a newly
      identified serine protease that is secreted by the type II secretion system in
      Vibrio cholerae, belongs to this subfamily. VesB is likely produced as a zymogen
      because sequence alignment with trypsinogen identified a putative cleavage site
      for activation and a catalytic triad, His-Asp-Ser. Using synthetic peptides, VesB
      efficiently cleaved a trypsin substrate, but not chymotrypsin and elastase
      substrates. The reversible serine protease inhibitor, benzamidine, inhibited VesB
      and served as an immobilized ligand for VesB affinity purification, further
      indicating its relationship with trypsin-like enzymes. Consistent with this
      family of serine proteases, N-terminal sequencing implied that the propeptide is
      removed in the secreted form of VesB. Separate mutagenesis of the activation site
      and catalytic serine rendered VesB inactive, confirming the importance of these
      features for activity, but not for secretion. Similar to trypsin but, in contrast
      to thrombin and other coagulation factors, Na(+) did not stimulate the activity
      of VesB, despite containing the Tyr(250) signature. The crystal structure of
      catalytically inactive pro-VesB revealed that the protease domain is structurally
      similar to trypsinogen. The C-terminal domain of VesB was found to adopt an
      immunoglobulin (Ig)-fold that is structurally homologous to Ig-folds of other
      extracellular Vibrio proteins. Possible roles of the Ig-fold domain in stability,
      substrate specificity, cell surface association, and type II secretion of VesB,
      the first bacterial multidomain trypsin-like protease with known structure, are
      discussed. 

PMID- 24459148
TI  - Defining the functional boundaries of the murine alpha1,3-fucosyltransferase Fut7
      reveals a remarkably compact locus.
AB  - Fut7 encodes an alpha1,3-fucosyltransferase critical for biosynthesis of glycan
      ligands for all three selectins. Consistent with this function, Fut7 expression
      is limited to hematopoietic cells and high endothelial cells which express
      selectin ligands. Mechanisms that govern Fut7 expression are poorly defined. To
      begin to understand the molecular genetic basis for transcriptional regulation of
      Fut7, a transgenic, gain-of-function, genetic complementation approach in mice
      was used to define the "functional boundaries" of the murine Fut7 locus, defined
      here as any uninterupted stretch of genomic DNA that contains all cis-acting
      genetic elements essential for accurate physiologic expression. A 12.7-kb
      contiguous genomic interval, which lies completely between the highly conserved
      flanking Npdc1 and Abca2 loci on chromosome 2 and which contains the complete
      transcriptional unit plus ~7.4 kb upstream of the transcriptional start site and
      ~2 kb downstream of the transcriptional termination and polyadenylation sites,
      was used as a transgene (Tg) on a Fut7 null background. Tg+ mice exhibited
      restoration of Fut7 gene expression and physiologic levels of selectin ligand
      expression and function on neutrophils, activated T cells, and high endothelial
      cells and corrected the functional defects in these cells found in Fut7 null mice
      without leading to detectable expression of Fut7 in normally non-expressing
      tissues. These results demonstrate that all genetic information essential for
      appropriate and selective expression of Fut7 in diverse cell types and in
      response to distinct developmental signals is contained within this comparatively
      small genetic region. 

PMID- 24459149
TI  - Structures of complexes of a metal-independent glycosyltransferase GT6 from
      Bacteroides ovatus with UDP-N-acetylgalactosamine (UDP-GalNAc) and its hydrolysis
      products.
AB  - Mammalian members of glycosyltransferase family 6 (GT6) of the CAZy database have
      a GT-A fold containing a conserved Asp-X-Asp (DXD) sequence that binds an
      essential metal cofactor. Bacteroides ovatus GT6a represents a GT6 clade found in
      more than 30 Gram-negative bacteria that is similar in sequence to the catalytic
      domains of mammalian GT6, but has an Asn(95)-Ala-Asn(97) (NXN) sequence
      substituted for the DXD motif and metal-independent catalytic activity. Co
      crystals of a low activity mutant of BoGT6a (E192Q) with UDP-GalNAc contained
      protein complexes with intact UDP-GalNAc and two forms with hydrolysis products
      (UDP plus GalNAc) representing an initial closed complex and later open form
      primed for product release. Two cationic residues near the C terminus of BoGT6a,
      Lys(231) and Arg(243), interact with the diphosphate moiety of UDP-GalNAc, but
      only Lys(231) interacts with the UDP product and may function in leaving group
      stabilization. The amide group of Asn(95), the first Asn of the NXN motif,
      interacts with the ribose moiety of the substrate. This metal-independent GT6
      resembles its metal-dependent homologs in undergoing conformational changes on
      binding UDP-GalNAc that arise from structuring the C terminus to cover this
      substrate. It appears that in the GT6 family, the metal cofactor functions
      specifically in binding the UDP moiety in the donor substrate and transition
      state, actions that can be efficiently performed by components of the polypeptide
      chain. 

PMID- 24459151
TI  - Palliative care for heart failure: challenges and opportunities.

PMID- 24459150
TI  - Structure and identification of a pterin dehydratase-like protein as a ribulose
      bisphosphate carboxylase/oxygenase (RuBisCO) assembly factor in the alpha
      carboxysome.
AB  - Carboxysomes are proteinaceous bacterial microcompartments that increase the
      efficiency of the rate-limiting step in carbon fixation by sequestering reaction
      substrates. Typically, alpha-carboxysomes are genetically encoded as a single
      operon expressing the structural proteins and the encapsulated enzymes of the
      microcompartment. In addition, depending on phylogeny, as many as 13 other genes
      are found to co-occur near or within alpha-carboxysome operons. One of these
      genes codes for a protein with distant homology to pterin-4alpha-carbinolamine
      dehydratase (PCD) enzymes. It is present in all alpha-carboxysome containing
      bacteria and has homologs in algae and higher plants. Canonical PCDs play an
      important role in amino acid hydroxylation, a reaction not associated with carbon
      fixation. We determined the crystal structure of an alpha-carboxysome PCD-like
      protein from the chemoautotrophic bacterium Thiomonas intermedia K12, at 1.3-A
      resolution. The protein retains a three-dimensional fold similar to canonical
      PCDs, although the prominent active site cleft present in PCD enzymes is
      disrupted in the alpha-carboxysome PCD-like protein. Using a cell-based
      complementation assay, we tested the PCD-like proteins from T. intermedia and two
      additional bacteria, and found no evidence for PCD enzymatic activity. However,
      we discovered that heterologous co-expression of the PCD-like protein from
      Halothiobacillus neapolitanus with RuBisCO and GroELS in Escherichia coli
      increased the amount of soluble, assembled RuBisCO recovered from cell lysates
      compared with co-expression of RuBisCO with GroELS alone. We conclude that this
      conserved PCD-like protein, renamed here alpha-carboxysome RuBisCO assembly
      factor (or acRAF), is a novel RuBisCO chaperone integral to alpha-carboxysome
      function. 

PMID- 24459152
TI  - Phase separation of myelin sheath in Triton X-114 solution: predominant
      localization of the 21.5-kDa isoform of myelin basic protein in the lipid raft
      associated domain.
AB  - Myelin basic protein (MBP) isoforms in the myelin sheath are known to have
      distinct intracellular expression patterns, which are profoundly related to
      functional specificity. Determining the differential localization of MBP isoforms
      is therefore important for understanding their pathophysiological roles. In this
      study, we have developed a new method for phase separation of myelin. The non
      ionic detergent Triton X-114 is used to solubilize myelin sheath which then
      undergoes phase separation to yield four fractions. The lipid raft-associated
      proteins and lipids in each fraction were analysed by immunoblotting and lipid
      analysis, respectively. The present method gives two lipid raft-enriched
      fractions, one of them was found to contain only lipid raft-associated
      galactocerebroside and cholesterol as the major lipids. The 21.5-kDa MBP isoforms
      (21.5 MBP), both unphosphorylated and phosphorylated, were exclusively contained
      in this fraction. Phosphorylated 21.5 MBP (21.5 pMBP) has been shown to
      specifically disappear from demyelinated loci. The present analytical method
      clearly indicated that disappearance of 21.5 pMBP corresponded to demyelination
      and its reappearance corresponded to prevention of demyelination. Demyelination
      was also associated with aging and was prevented by the myelin-protecting herbal
      medicine, Chinpi, a type of dried citrus peel. 

PMID- 24459156
TI  - Metformin causing vitamin B12 deficiency: a guilty verdict without sufficient
      evidence.

PMID- 24459154
TI  - Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a
      systematic review and a dose-response meta-analysis.
AB  - OBJECTIVE: Previous meta-analyses identified an inverse association of coffee
      consumption with the risk of type 2 diabetes. However, an updated meta-analysis
      is needed because new studies comparing the trends of association for caffeinated
      and decaffeinated coffee have since been published. RESEARCH DESIGN AND METHODS:
      PubMed and Embase were searched for cohort or nested case-control studies that
      assessed the relationship of coffee consumption and risk of type 2 diabetes from
      1966 to February 2013. A restricted cubic spline random-effects model was used.
      RESULTS: Twenty-eight prospective studies were included in the analysis, with
      1,109,272 study participants and 45,335 cases of type 2 diabetes. The follow-up
      duration ranged from 10 months to 20 years. Compared with no or rare coffee
      consumption, the relative risk (RR; 95% CI) for diabetes was 0.92 (0.90-0.94),
      0.85 (0.82-0.88), 0.79 (0.75-0.83), 0.75 (0.71-0.80), 0.71 (0.65-0.76), and 0.67
      (0.61-0.74) for 1-6 cups/day, respectively. The RR of diabetes for a 1 cup/day
      increase was 0.91 (0.89-0.94) for caffeinated coffee consumption and 0.94 (0.91
      0.98) for decaffeinated coffee consumption (P for difference = 0.17).
      CONCLUSIONS: Coffee consumption was inversely associated with the risk of type 2
      diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee was
      associated with reduced diabetes risk.

PMID- 24459157
TI  - Clinical characteristics of patients who report incorrect data of home-measured
      blood pressure.

PMID- 24459158
TI  - The mSCOFF for screening disordered eating in pediatric type 1 diabetes.

PMID- 24459159
TI  - Self-reported autoimmune disease by sex in the diabetes control and complications
      trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study.

PMID- 24459160
TI  - Do the new threshold levels for the diagnosis of gestational diabetes mellitus
      correctly identify women at risk?

PMID- 24459161
TI  - Review of the effect of internet therapeutic intervention in patients with type 1
      and type 2 diabetes.

PMID- 24459162
TI  - Comment on zhu et Al. Fasting plasma glucose at 24-28 weeks to screen for
      gestational diabetes mellitus: new evidence from china. Diabetes care
      2013;36:2038-2040.

PMID- 24459163
TI  - Response to comment on zhu et Al. Fasting plasma glucose at 24-28 weeks to screen
      for gestational diabetes mellitus: new evidence from china. Diabetes care
      2013;36:2038-2040.

PMID- 24459164
TI  - Comment on knowler et Al. Preventing diabetes in american Indian communities.
      Diabetes care 2013;36:1820-1822.

PMID- 24459165
TI  - Response to comment on knowler et Al. Preventing diabetes in american Indian
      communities. Diabetes care 2013;36:1820-1822.

PMID- 24459166
TI  - Comment on Kulkarni et Al. Maternal lipids are as important as glucose for fetal
      growth: findings from the pune maternal nutrition study. Diabetes care
      2013;36:2706-2713.

PMID- 24459167
TI  - Response to comment on Kulkarni et Al. Maternal lipids are as important as
      glucose for fetal growth: findings from the pune maternal nutrition study.
      Diabetes care 2013;36:2706-2713.

PMID- 24459168
TI  - Comment. Is incretin-based therapy ready for the care of hospitalized patients
      with type 2 diabetes?

PMID- 24459169
TI  - Response to comment. Is incretin-based therapy ready for the care of hospitalized
      patients with type 2 diabetes?

PMID- 24459170
TI  - Comment on d'Emden. Do the new threshold levels for the diagnosis of gestational
      diabetes mellitus correctly identify women at risk? Diabetes Care 2014;37:e30.

PMID- 24459171
TI  - Whipple's in the valleys: a case of Whipple's with thrombocytopenia and
      endocarditis.
AB  - INTRODUCTION: This case report details the second described case of Whipple's
      disease-related thrombocytopenia in the medical literature. Whipple's disease is
      a rare multisystem infection caused by the actinomycete Tropheryma whipplei,
      first described by George Whipple in 1907. The key clinical manifestations are
      weight loss, diarrhoea and malabsorption, but arthralgia and endocarditis are
      also well described. CASE PRESENTATION: A 62-year-old Caucasian female presented
      with weight loss, anaemia and behavioural changes but denied any abdominal
      symptoms. Thrombocytopenia subsequently developed rapidly. Bone marrow
      examination showed abundant megakaryocytes in keeping with peripheral platelet
      sequestration. In addition, there was significant polyclonal plasmacytosis. She
      was also found to have a 1.6 cm tricuspid vegetation. The diagnosis was confirmed
      by presence of foamy macrophages on duodenal biopsy, positive periodic acid
      Schiff staining and visualisation of T whipplei actinomycetes on electron
      microscopy. Tissue PCR performed mid-treatment showed traces of T whipplei DNA.
      The infection was treated with a 2-week intravenous course of ceftriaxone
      followed by 12 months of oral co-trimoxazole. The thrombocytopenia and anaemia
      resolved rapidly with antibiotic therapy, her behaviour returned to normal and
      she remains clinically well. CONCLUSIONS: This report confirms the association of
      thrombocytopenia with Whipple's disease, likely due to peripheral platelet
      sequestration, which resolves rapidly with treatment. In patients with a long
      history of unintended weight loss, Whipple's disease is a rare but important
      differential diagnosis as it is ultimately fatal if left untreated.

PMID- 24459172
TI  - Task-oriented exercises and early full weight-bearing contribute to improving
      disability after total hip replacement: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of an in-hospital programme based on task
      oriented exercises associated with early full weight-bearing in patients with
      multiple comorbidities undergoing total hip replacement. DESIGN: Randomized
      controlled trial. SETTING: Specialised rehabilitation centre. SUBJECTS: A total
      of 100 patients (mean age of 69 (8) years; 40 males, 60 females). INTERVENTIONS:
      The experimental group underwent task-oriented exercises and was encouraged to
      abandon any walking aids by the end of their in-hospital stay. The control group
      underwent open chain kinetic exercises, and was recommended to use partial weight
      bearing and walking aids until three months after surgery. Both groups
      individually followed programmes of 90-minute sessions five times a week for
      three weeks. OUTCOME MEASURES: Western Ontario and McMaster Universities
      Osteoarthritis Index, Pain Numerical Rating Scale, Functional Independence
      Measure, and Short-Form Health Survey. The participants were evaluated before,
      after training, and after a further 12 months. RESULTS: There were no significant
      between-group differences at baseline. After training, a between-group difference
      of 12 points was found for the Western Ontario and McMaster Universities
      Osteoarthritis Index - functional subscale, indicating a clinically tangible
      treatment effect on disability. The Functional Independence Measure increased by
      31 and 15 points in the experimental and control group, respectively. A linear
      mixed model revealed significant effects of time, group, and time by group
      interaction on disability, pain, activities of daily living, and most of the
      physical quality of life domains. CONCLUSION: Task-oriented exercises associated
      with early full weight-bearing improve disability, pain, activities of daily
      living, and quality of life after total hip replacement.

PMID- 24459173
TI  - Prehabilitation program for elective coronary artery bypass graft surgery
      patients: a pilot randomized controlled study.
AB  - OBJECTIVE: To determine the feasibility of a cardiac prehabilitation (Prehab)
      program for patients waiting for elective coronary artery bypass graft (CABG).
      DESIGN: A two-group parallel randomized controlled trial. SETTING: Medical
      fitness facility. SUBJECTS: Seventeen preoperative elective CABG surgery patients
      were randomized to standard care (n = 9) or Prehab (n = 8). INTERVENTION:
      Standard care: three-hour preassessment appointment. Prehab: exercise and
      education classes for 60 minutes/day, twice weekly for at least four weeks. MAIN
      MEASURES: Data were collected at baseline, one week preoperatively, and three
      months postoperatively. The primary outcome measure was walking distance using a
      6-minute walk test. Secondary outcome variables included 5-meter gait speed, and
      cardiac rehabilitation attendance three months postoperatively. RESULTS: Fifteen
      patients (standard care, n = 7; Prehab, n = 8) completed the study. No Prehab
      patients developed cardiac symptoms during study participation. Walking distance
      remained unchanged in the standard care group; whereas, the Prehab group
      increased their walking distance to mean +/- SD 474 +/-101 and 487 +/-106 m at
      the preoperative and three month postoperative assessments (p < 0.05). Gait speed
      was unchanged in the standard care group, but improved in the Prehab group by 27%
      and 33% preoperatively and three months postoperatively, respectively (p < 0.05).
      Enrollment in cardiac rehabilitation three months postoperatively was higher for
      Prehab participants (100%) than standard care participants (43%; p < 0.05).
      CONCLUSION: These data provide evidence for the feasibility of a Prehab
      intervention to improve the health status of patients waiting for elective CABG
      surgery. A larger trial of 92 patients will be utilized to demonstrate the safety
      and efficacy of Prehab.

PMID- 24459174
TI  - Inconsistent classification of pusher behaviour in stroke patients: a direct
      comparison of the Scale for Contraversive Pushing and the Burke Lateropulsion
      Scale.
AB  - OBJECTIVE: To compare the classification of two clinical scales for assessing
      pusher behaviour in a cohort of stroke patients. DESIGN: Observational case
      control study. SETTING: Inpatient stroke rehabilitation unit. SUBJECTS: A sample
      of 23 patients with hemiparesis due to a unilateral stroke (1.6 +/- 0.7 months
      post stroke). METHODS: Immediately before and after three different
      interventions, the Scale for Contraversive Pushing and the Burke Lateropulsion
      Scale were applied in a standardized procedure. RESULTS: The diagnosis of pusher
      behaviour on the basis of the Scale for Contraversive Pushing and the Burke
      Lateropulsion Scale differed significantly (chi2 = 54.260, p < 0.001) resulting
      in inconsistent classifications in 31 of 138 cases. Changes immediately after the
      interventions were more often detected by the Burke Lateropulsion Scales than by
      the Scale for Contraversive Pushing (chi2 = 19.148, p < 0.001). All cases with
      inconsistent classifications showed no pusher behaviour on the Scale for
      Contraversive Pushing, but pusher behaviour on the Burke Lateropulsion Scale.
      64.5% (20 of 31) of them scored on the Burke Lateropulsion Scale on the standing
      and walking items only. CONCLUSIONS: The Burke Lateropulsion Scale is an
      appropriate alternative to the widely used Scale for Contraversive Pushing to
      follow-up patients with pusher behaviour (PB); it might be more sensitive to
      detect mild pusher behaviour in standing and walking.

PMID- 24459175
TI  - Built environment change: a framework to support health-enhancing behaviour
      through environmental policy and health research.
AB  - As research examining the effect of the built environment on health accelerates,
      it is critical for health and planning researchers to conduct studies and make
      recommendations in the context of a robust theoretical framework. We propose a
      framework for built environment change (BEC) related to improving health. BEC
      consists of elements of the built environment, how people are exposed to and
      interact with them perceptually and functionally, and how this exposure may
      affect health-related behaviours. Integrated into this framework are the legal
      and regulatory mechanisms and instruments that are commonly used to effect change
      in the built environment. This framework would be applicable to medical research
      as well as to issues of policy and community planning. 

PMID- 24459176
TI  - Considerations in the design of randomized trials to screen for type 2 diabetes.
AB  - Background Randomized controlled trials (RCTs) are the most robust and valid
      approach to evaluate screening for diseases. Many in the diabetes research
      community have advocated sole reliance on RCTs for designing diabetes screening
      policies. However, the challenges of conducting RCTs of screening for type 2
      diabetes may have been underappreciated. Purpose Discuss the key theoretical
      concepts and practical challenges of designing and conducting RCTs of diabetes
      screening. Methods Narrative and critical review of the literature pertaining to
      the theory and practice of designing and conducting RCTs of diabetes screening.
      Results We present the theoretical basis of a diabetes screening trial, using
      concepts developed mainly in studies of cancer screening and illustrations from
      the Cambridge component of the Anglo Danish Dutch Study of Intensive Treatment In
      peOple with screeN-detected diabetes in primary care (ADDITION-Cambridge), the
      only extant trial of diabetes screening. We examine design issues, including the
      appropriate trial question, choice of design, and duration of follow-up, and
      address aspects of trial implementation, including recruitment, randomization,
      endpoint determination, sample size requirements, and screening interval.
      Limitations The limited number of trials of diabetes screening did not permit us
      to illustrate many of the practical difficulties one encounters when implementing
      theoretical concepts. Conclusion When diabetes screening trials are planned, we
      suggest careful consideration to potential areas of practical difficulty,
      especially the need for particularly large sample sizes and extended follow-up,
      and the choice of appropriate outcomes and screening intervals.

PMID- 24459177
TI  - The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia.
AB  - Increased concentrations of bilirubin glucuronides in blood plasma indicate
      hepatocellular dysfunction. Elucidation of the transport processes of bilirubin
      conjugates across the basolateral (sinusoidal) and the canalicular plasma
      membrane domains of hepatocytes has decisively contributed to our current
      understanding of the molecular basis of conjugated hyperbilirubinemia in human
      liver diseases. Under normal conditions, unconjugated bilirubin is taken up into
      hepatocytes by transporters of the organic anion-transporting polypeptide (OATP)
      family, followed by conjugation with glucuronic acid, and ATP-dependent transport
      into bile. This efflux across the canalicular membrane is mediated by multidrug
      resistance protein 2 (MRP2 or ABCC2), which is a 190-kDa glycoprotein
      transporting with high affinity and efficiency monoglucuronosyl bilirubin and
      bisglucuronosyl bilirubin into bile. MRP2 is hereditarily deficient in human
      Dubin-Johnson syndrome. Under pathophysiological conditions such as cholestatic
      liver injury and MRP2 inhibition, the basolateral efflux pump multidrug
      resistance protein 3 (MRP3 or ABCC3) is responsible for the occurrence of
      conjugated hyperbilirubinemia. MRP3 is a glycoprotein with a similar molecular
      mass as MRP2, with 48% amino acid identity, and with overlapping substrate
      specificity. Human MRP3 is the only basolateral efflux pump shown to transport
      bilirubin glucuronides. In human and rat hepatocytes, MRP3/Mrp3 is strongly
      upregulated under conditions of cholestasis and MRP2 deficiency. This is in line
      with the concept that basolateral efflux pumps of the hepatocyte compensate for
      impaired canalicular efflux of compounds into bile and contribute to balance the
      rate of uptake or synthesis of compounds in hepatocytes with the capacity for
      efflux into bile. 

PMID- 24459178
TI  - Edoxaban transport via P-glycoprotein is a key factor for the drug's disposition.
AB  - Edoxaban (the free base of DU-176b), an oral direct factor Xa inhibitor, is
      mainly excreted unchanged into urine and feces. Because active membrane transport
      processes such as active renal secretion, biliary excretion, and/or intestinal
      secretion, and the incomplete absorption of edoxaban after oral administration
      have been observed, the involvement of drug transporters in the disposition of
      edoxaban was investigated. Using a bidirectional transport assay in human colon
      adenocarcinoma Caco-2 cell monolayers, we observed the vectorial transport of
      [(14)C]edoxaban, which was completely inhibited by verapamil, a strong P
      glycoprotein (P-gp) inhibitor. In an in vivo study, an increased distribution of
      edoxaban to the brain was observed in Mdr1a/1b knockout mice when compared with
      wild-type mice, indicating that edoxaban is a substrate for P-gp. However, there
      have been no observations of significant transport of edoxaban by renal or
      hepatic uptake transporters, organic anion transporter (OAT)1, OAT3, organic
      cation transporter (OCT)2, or organic anion transporting polypeptide (OATP)1B1.
      Edoxaban exhibited no remarkable inhibition of OAT1, OAT3, OCT1, OCT2, OATP1B1,
      OATP1B3, or P-gp up to 30 MUM; therefore, the risk of clinical drug-drug
      interactions due to any edoxaban-related transporter inhibition seems to be
      negligible. Our results demonstrate that edoxaban is a substrate of P-gp but not
      of other major uptake transporters tested. Because metabolism is a minor
      contributor to the total clearance of edoxaban and strong P-gp inhibitors clearly
      impact edoxaban transport, the P-gp transport system is a key factor for
      edoxaban's disposition. 

PMID- 24459179
TI  - UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues.
AB  - The UDP-glucuronosyltransferase (UGT) 2B subfamily of enzymes plays an important
      role in the metabolism of numerous endogenous and exogenous compounds, including
      various carcinogens present in tobacco smoke. The goal of the present study was
      to examine the levels of expression of individual UGT2B genes in various tissues
      that are targets for tobacco carcinogenesis. Using MT-ATP6 as the experimentally
      validated housekeeping gene, the highest extrahepatic expression of UGT2B genes
      was observed in human tonsil, with UGT2B expression levels similar to that
      observed in human liver. UGT2B17 exhibited high relative expression in most
      tissues examined, including lung, most tissues of the aerodigestive tract, and
      pancreas. UGT2B7 expression was highest in pancreas but low or undetectable in
      most other tissues examined. UGT2B10 expression was high in both tonsil and
      tongue. There was wide variability between individuals in the magnitude of
      expression in each tissue site, and there were strong correlations between UGT2B
      expression levels in different individuals within many of the tissue sites,
      suggesting coordinated regulation of UGT2B gene expression in extrahepatic
      tissues. In the liver, UGTs 2B4, 2B7, 2B10, and 2B15 were significantly
      correlated with each other (all r(2) > 0.70, P < 0.0001). In all examined tissues
      of the aerodigestive tract, UGTs 2B10, 2B11, and 2B17 exhibited a strong
      correlation with each other (all r(2) > 0.75, P < 0.05). UGTs 2B7 and 2B10
      exhibited a strong inverse correlation in the pancreas (r(2) = -0.95, P < 0.01).
      These data suggest that specific UGT2B enzymes important in tobacco carcinogen
      metabolism are expressed and coordinately regulated in various target sites for
      tobacco-related cancers. 

PMID- 24459182
TI  - The four faces of autophagy: implications for cancer therapy.
AB  - It is generally thought that autophagy has two primary and opposing functions in
      tumor cells in response to stress induced by chemotherapy or radiation. One is
      the cytoprotective function that can in theory be inhibited for therapeutic
      advantage by sensitizing the cells to these treatment modalities. The other is
      the cytotoxic function that is generally not observed with conventional treatment
      modalities, but that may function to promote tumor cell killing either alone or
      in association with apoptosis. In this commentary/review, we advance the premise
      that autophagy is actually populated by at least two additional players. One we
      have termed the nonprotective form of autophagy, where the cell is apparently
      carrying out autophagy-mediated degradative functions, but where autophagy
      inhibition does not lead to perceptible alterations in drug or radiation
      sensitivity. The other is what we now term the cytostatic form of autophagy in
      that its activation results in prolonged growth inhibition as well as reduced
      clonogenic survival (loss of reproductive capacity) but in the absence of actual
      loss of cell viability through apoptosis or necrosis; however, as is the case
      with cytototoxic autophagy, inhibition of cytostatic autophagy protects the tumor
      cell from the agent (drugs or radiation) that promotes the autophagic response.
      In view of current clinical efforts to exploit autophagy inhibition as a
      therapeutic strategy for sensitization of malignancies to chemotherapy and
      radiation, it is critical to recognize that if chemotherapy and/or radiation
      actually promote autophagy in patient tumors, the autophagy is not of necessity
      cytoprotective in function.

PMID- 24459181
TI  - The structural basis of PI3K cancer mutations: from mechanism to therapy.
AB  - While genetic alteration in the p85alpha-p110alpha (PI3K) complex represents one
      of the most frequent driver mutations in cancer, the wild-type complex is also
      required for driving cancer progression through mutations in related pathways.
      Understanding the mechanistic basis of the function of the phosphoinositide 3
      kinase (PI3K) is essential for designing optimal therapeutic targeting
      strategies. Recent structural data of the p85alpha/p110alpha complex unraveled
      key insights into the molecular mechanisms of the activation of the complex and
      provided plausible explanations for the well-established biochemical data on
      p85/p110 dimer regulation. A wealth of biochemical and biologic information
      supported by recent genetic findings provides a strong basis for additional p110
      independent function of p85alpha in the regulation of cell survival. In this
      article, we review the structural, biochemical, and biologic mechanisms through
      which p85alpha regulates the cancer cell life cycle with an emphasis on the
      recently discovered genetic alterations in cancer. As cancer progression is
      dependent on multiple biologic processes, targeting key drivers such as the PI3K
      may be required for efficacious therapy of heterogeneous tumors typically present
      in patients with late-stage disease.

PMID- 24459183
TI  - Hydrodynamics and collective behavior of the tethered bacterium Thiovulum majus.
AB  - The ecology and dynamics of many microbial systems, particularly in mats and
      soils, are shaped by how bacteria respond to evolving nutrient gradients and
      microenvironments. Here we show how the response of the sulfur-oxidizing
      bacterium Thiovulum majus to changing oxygen gradients causes cells to organize
      into large-scale fronts. To study this phenomenon, we develop a technique to
      isolate and enrich these bacteria from the environment. Using this enrichment
      culture, we observe the formation and dynamics of T. majus fronts in oxygen
      gradients. We show that these dynamics can be understood as occurring in two
      steps. First, chemotactic cells moving up the oxygen gradient form a front that
      propagates with constant velocity. We then show, through observation and
      mathematical analysis, that this front becomes unstable to changes in cell
      density. Random perturbations in cell density create oxygen gradients. The
      response of cells magnifies these gradients and leads to the formation of
      millimeter-scale fluid flows that actively pull oxygenated water through the
      front. We argue that this flow results from a nonlinear instability excited by
      stochastic fluctuations in the density of cells. Finally, we show that the
      dynamics by which these modes interact can be understood from the chemotactic
      response of cells. These results provide a mathematically tractable example of
      how collective phenomena in ecological systems can arise from the individual
      response of cells to a shared resource. 

PMID- 24459184
TI  - Unified superresolution experiments and stochastic theory provide mechanistic
      insight into protein ion-exchange adsorptive separations.
AB  - Chromatographic protein separations, immunoassays, and biosensing all typically
      involve the adsorption of proteins to surfaces decorated with charged,
      hydrophobic, or affinity ligands. Despite increasingly widespread use throughout
      the pharmaceutical industry, mechanistic detail about the interactions of
      proteins with individual chromatographic adsorbent sites is available only via
      inference from ensemble measurements such as binding isotherms, calorimetry, and
      chromatography. In this work, we present the direct superresolution mapping and
      kinetic characterization of functional sites on ion-exchange ligands based on
      agarose, a support matrix routinely used in protein chromatography. By
      quantifying the interactions of single proteins with individual charged ligands,
      we demonstrate that clusters of charges are necessary to create detectable
      adsorption sites and that even chemically identical ligands create adsorption
      sites of varying kinetic properties that depend on steric availability at the
      interface. Additionally, we relate experimental results to the stochastic theory
      of chromatography. Simulated elution profiles calculated from the molecular-scale
      data suggest that, if it were possible to engineer uniform optimal interactions
      into ion-exchange systems, separation efficiencies could be improved by as much
      as a factor of five by deliberately exploiting clustered interactions that
      currently dominate the ion-exchange process only accidentally. 

PMID- 24459185
TI  - Prerequisites to proton transport in the bacterial ClC-ec1 Cl-/H+ exchanger.

PMID- 24459186
TI  - Refining a key metabolic innovation in Escherichia coli.

PMID- 24459187
TI  - Inflammation promotes prostate differentiation.

PMID- 24459188
TI  - What is the current state of care for older people with dementia in general
      hospitals? A literature review.
AB  - This paper summarises a literature review focusing on the literature directly
      pertaining to the acute care of older people with dementia in general hospitals
      from 2007 onwards. Following thematic analysis, one overarching theme emerged:
      the consequences of being in hospital with seven related subthemes.
      Significantly, this review highlights that overall there remains mostly negative
      consequences and outcomes for people with dementia when they go into general
      hospitals. Although not admitted to hospital directly due to dementia, there are
      usually negative effects on the dementia condition from hospitalisation. The
      review suggests this is primarily because there is a tension between
      prioritisation of acute care for existing co-morbidities and person-centred
      dementia care. This is complicated by insufficient understanding of what
      constitutes person-centred care in an acute care context and a lack of the
      requisite knowledge and skills set in health care practitioners. The review also
      reveals a worrying lack of evidence for the effectiveness of mental health
      liaison posts and dementia care specialist posts in nursing. Finally, although
      specialist posts such as liaison and clinical nurse specialists and specialist
      units/shared care wards can enhance quality of care and reduce adverse
      consequences of hospitalisation (they do not significantly) impact on reducing
      length of stay or the cost of care. 

PMID- 24459189
TI  - The peripheral cannabinoid receptor 1 antagonist VD60 efficiently inhibits carbon
      tetrachloride-intoxicated hepatic fibrosis progression.
AB  - This study investigated a peripheral selective CB1 antagonist 3,4,22-3
      demethoxycarbonyl-3-hydroxylmethyl-4-deacetyl-vindoline 3,4-thionocarbonate
      (VD60) that efficiently inhibited hepatic fibrosis with lower psychological side
      effects. A competitive radiolabeled ligand binding experiment and 3'-5'-cyclic
      adenosine monophosphate (cAMP) response element-driven luciferase analysis were
      performed to evaluate the antagonistic activity of VD60. Cell viability and
      collagen production were examined in the human hepatic stellate cell (HSC) line
      LX-2 and primary cultured rat HSCs. The antifibrotic effects of VD60 were
      investigated in a CCl4-induced liver fibrosis mouse model. The concentration of
      VD60 in the blood and the brain was determined by high-performance liquid
      chromatography-mass spectrum analysis. Furthermore, the potential underlying
      mechanisms of VD60 were investigated by Western blot. VD60 selectively competed
      with the radiolabeled CB1 agonist to bind to CB1. VD60 antagonized CB1 agonist
      induced Akt phosphorylation and increased the accumulation of intracellular cAMP.
      VD60 strongly reduced the expression of alpha2(I) pro-collagen mRNA and exerted
      potent antiproliferative effects on primary HSCs and LX-2 cells. The inhibition
      of reactive oxygen species production and phosphorylation of Akt, extracellular
      signal-regulated kinase (ERK), and Smad3 may explain the underlying mechanisms
      behind the antiproliferative effect of VD60. Moreover, the in vivo antifibrotic
      activity of VD60 was confirmed in a CCl4-induced liver fibrosis mouse model. Most
      importantly, the concentration of VD60 in the peripheral blood was much higher
      than in the brain, suggesting that VD60 could act as a novel peripheral CB1
      antagonist to efficiently inhibit hepatic fibrosis and could be used as a lead
      compound with low brain side effects in peripheral antifibrotic agents.

PMID- 24459190
TI  - Blockade of visfatin induction by oleanolic acid via disturbing IL-6-TRAF6-NF
      kappaB signaling of adipocytes.
AB  - Oleanolic acid is a pentacyclic triterpenoid naturally present in foods and
      medicinal plants with anticancer, antioxidant, and antiaging properties. The
      current study elucidated that oleanolic acid inhibited the production of insulin
      mimetic and inflammatory adipokine of visfatin during adipogenic differentiation
      of 3T3-L1 adipocytes. Adipocytes were cultured in an adipogenic media with and
      without 1-25 uM oleanolic acid up to 8 days for differentiation. The cellular
      expression and secretion of visfatin was markedly enhanced in differentiating
      adipocytes, which was dose-dependently attenuated by 1-25 uM oleanolic acid.
      Secretion of interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 was
      highly elevated during differentiation, which was much earlier than visfatin
      production of adipocytes. The visfatin production was secondary to inflammatory
      IL-6 and MIP-2. This study further elucidated that nuclear factor-kappaB (NF
      kappaB) signaling was responsible for cellular production of visfatin. NF-kappaB
      was activated by translocating into the nucleus with increased phosphorylation of
      inhibitory kappaB (IkappaB), which was disturbed by oleanolic acid. Cellular
      expression of tumor necrosis factor receptor associated factor 6 (TRAF6), a NF
      kappaB upstream, was upregulated in parallel with transactivation with NF-kappaB.
      The TRAF6 induction required the auto-stimulation of inflammatory IL-6 and MIP-2.
      These results demonstrate that oleanolic acid inhibited visfatin and its
      inflammatory response during adipocyte differentiation through blocking IL-6
      TRAF6-NF-kappaB signaling. Therefore, oleanolic acid may be a potent therapeutic
      agent targeting against adipogenesis and visfatin-linked inflammation.

PMID- 24459191
TI  - Intestinal immunity is a determinant of clearance of poliovirus after oral
      vaccination.
AB  - BACKGROUND: Response to challenge with live, attenuated, oral polio vaccine (OPV)
      is a measure of immunity induced by prior immunization. METHODS: Using stool
      samples from a study from Oman in which an initial schedule of inactivated polio
      vaccine (IPV) was followed by an OPV type 1 challenge, we quantitated virus shed,
      sequenced capsid proteins of recovered virus, and developed assays for
      neutralization of poliovirus and mucosal immunoglobulin A (IgA) detection.
      RESULTS: Neutralizing activity correlated with detection of polio-specific IgA in
      stool suspensions collected 7 days after OPV type 1 challenge. Both
      neutralization and IgA in stool were associated with cessation of virus shedding
      by day 7. Rapid development of an IgA response with cessation of shedding
      suggests that IPV primed for the early response to challenge. Correlation of
      neutralization activity and IgA detection provides evidence that polio-specific
      IgA intestinal antibody is a determinant of mucosal shedding/transmission and
      that IgA functions through neutralization of virus. In contrast, neither presence
      nor quantity of serum or intestinal antibody induced by IPV prior to challenge
      correlated with cessation of shedding. CONCLUSIONS: These assays provide an
      opportunity to study other immunization schedules to gain a broader understanding
      of the appearance and duration of a protective mucosal response to polio
      vaccination.

PMID- 24459192
TI  - Increase in genogroup II.4 norovirus host spectrum by CagA-positive Helicobacter
      pylori infection.
AB  - BACKGROUND: Noroviruses (NoVs) represent a considerable public health burden.
      Despite their enormous genetic diversity, most outbreaks are due to the single
      GII.4 genotype, but the reasons for this are poorly understood. NoVs use histo
      blood group antigens (HBGAs) as attachment factors. Since HBGAs are present in
      saliva, binding of strains to saliva is commonly used as a surrogate for
      recognition of the gut surface by specific strains, although the relationship
      between saliva and gut tissue expression of HBGAs is not well defined. METHODS:
      The presence of fucosylated HBGAs in saliva and stomach biopsy specimens, as well
      as that of genogroup I.1 and genogroup II.4 virus-like particles, were compared
      in a series of 109 donors from Portugal. RESULTS: An overall good concordance
      between HBGA expression in saliva and stomach surface mucosa was observed.
      However, unexpected mucosal expression of alpha(1,2)fucosylated epitopes in
      nonsecretor individuals was frequently detected, allowing for GII.4 attachment.
      Although all individuals were infected with Helicobacter pylori, abnormal
      expression of alpha(1,2)fucosylated motifs and binding of GII.4 virus-like
      particles in nonsecretors' mucosa were associated with positivity for the H.
      pylori CagA virulence factor. CONCLUSIONS: Infection by CagA-positive H. pylori
      induces expression of GII.4 attachment factors in nonsecretors' mucosa, expanding
      the host range of these strains and thereby possibly contributing to their
      epidemiological dominance.

PMID- 24459193
TI  - Incidence and prevalence of pregnancy-related heart disease.
AB  - Worldwide, the numbers of women who have a pre-existing cardiovascular disease or
      develop cardiac problems during pregnancy are increasing and, due to the lack of
      evidenced-based data, this provides challenges for the treating physician.
      Cardiovascular disease in pregnancy is a complex topic as women can present
      either pre- or post-partum, due to a pre-existing heart disease such as operated
      on or unoperated on congenital heart disease, valvular heart disease, chronic
      hypertension, or familial dilated cardiomyopathy. Women often present with
      symptoms and signs of acute heart failure. On the other hand, there are diseases
      which are directly related to pregnancy, such as hypertensive disorders of
      pregnancy and peripartum cardiomyopathy, or where pregnancy increases risk of a
      disease as, for example, the risk of myocardial infarction. These diseases can
      have long-term implications to the life of the affected women and their families.
      There is, in particular, a paucity of data from developing countries of this
      unique disease pattern and its presentations. This review summarizes the current
      knowledge of the incidence and prevalence of pregnancy-related cardiovascular
      disease in women presenting pre- or post-partum. 

PMID- 24459194
TI  - Strategy of Daiichi Sankyo discovery research in oncology.
AB  - We would like to introduce Daiichi Sankyo's approach to developing cancer
      targeted medicines with special reference to the drug discovery strategy, global
      discovery activities and external research collaboration leading to generation of
      innovative drugs for cancer patients. We are developing 14 clinical projects for
      cancer treatment and three of them have been previously approved. These are
      mostly targeted for growth and survival signals of cancer cells. To overcome the
      drug resistance mechanism derived from the heterogeneous nature of cancer, we are
      developing selective inhibitors in three major clusters of signal pathways which
      may allow future rational combinations of oncology products. In addition to the
      main research facility in Japan, research sites in the EU and the USA provide us
      with different technical expertise and diversified ideas of drug discovery. To
      access novel drug targets, we are facilitating research collaboration with
      leading academia and successful cancer research scientists. In conclusion, we
      intend to focus more on developing innovative personalized medicines for better
      treatment of cancer. 

PMID- 24459195
TI  - Relaxing from dyspnoea.

PMID- 24459196
TI  - Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable
      polymer drug-eluting stents: a systematic review and Bayesian approach network
      meta-analysis.
AB  - BACKGROUND: The aim of this study was to compare the safety and efficacy of
      biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS),
      and durable-polymer DES in patients undergoing coronary revascularization, we
      performed a systematic review and network meta-analysis using a Bayesian
      framework. METHODS AND RESULTS: Study stents included BMS, paclitaxel-eluting
      (PES), sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt
      chromium everolimus-eluting (CoCr-EES), platinium-chromium everolimus-eluting
      (PtCr-EES), resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents
      (BP-BES). After a systematic electronic search, 113 trials with 90 584 patients
      were selected. The principal endpoint was definite or probable stent thrombosis
      (ST) defined according to the Academic Research Consortium within 1 year.
      RESULTS: Biodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible
      interval (CrI), 0.33-0.90], SES (OR, 0.53; 95% CrI, 0.38-0.73), CoCr-EES (OR,
      0.34; 95% CrI, 0.23-0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10-0.90) were all
      superior to BMS in terms of definite or probable ST within 1 year. Cobalt
      chromium everolimus-eluting stents demonstrated the lowest risk of ST of all
      stents at all times after stent implantation. Biodegradable polymer-biolimus
      eluting stents was associated with a higher risk of definite or probable ST than
      CoCr-EES (OR, 1.72; 95% CrI, 1.04-2.98). All DES reduced the need for repeat
      revascularization, and all but PES reduced the risk of myocardial infarction
      compared with BMS. CONCLUSIONS: All DESs but PES and ZES-E were superior to BMS
      in terms of ST within 1 year. Cobalt-chromium everolimus-eluting stents was safer
      than any DES even including BP-BES. Our results suggest that not only the
      biodegradability of polymer, but the optimal combination of stent alloy, design,
      strut thickness, polymer, and drug all combined determine the safety of DES.

PMID- 24459199
TI  - Corrigendum to: Retraction of: Cardiopulse article, 'Research failure can result
      in lost lives'.

PMID- 24459198
TI  - Imaging to select and guide transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is indicated for patients with
      severe aortic stenosis and high or prohibitive surgical risk. Patients' selection
      requires clinical and anatomical selection criteria, being the later determined
      by multimodality imaging evaluation. Echocardiography, multislice computed
      tomography (MSCT), angiography, and cardiovascular magnetic resonance (CMR) are
      the methods available to determine the anatomical suitability for the procedure.
      Imaging assists in the selection of bioprosthesis type, prosthetic sizing and in
      the decision of the best vascular access. In this review, we present our critical
      appraisal on the use of imaging to best patients' selection and procedure
      guidance in TAVI. 

PMID- 24459197
TI  - Central blood pressure: current evidence and clinical importance.
AB  - Pressure measured with a cuff and sphygmomanometer in the brachial artery is
      accepted as an important predictor of future cardiovascular risk. However,
      systolic pressure varies throughout the arterial tree, such that aortic (central)
      systolic pressure is actually lower than corresponding brachial values, although
      this difference is highly variable between individuals. Emerging evidence now
      suggests that central pressure is better related to future cardiovascular events
      than is brachial pressure. Moreover, anti-hypertensive drugs can exert
      differential effects on brachial and central pressure. Therefore, basing
      treatment decisions on central, rather than brachial pressure, is likely to have
      important implications for the future diagnosis and management of hypertension.
      Such a paradigm shift will, however, require further, direct evidence that
      selectively targeting central pressure, brings added benefit, over and above that
      already provided by brachial artery pressure. 

PMID- 24459200
TI  - Bilateral cotton wool spots after use of an endothelin receptor antagonist.
AB  - Ambrisentan (Letairis; Gilead Sciences, Foster City, CA) is an endothelin
      receptor antagonist approved by the U.S. Food and Drug Administration for the
      treatment of pulmonary arterial hypertension. The authors describe the occurrence
      of bilateral cotton wool spots soon after initiation of ambrisentan treatment in
      a 29-year-old woman. Fluorescein angiography, optical coherence tomography, and
      fundus autofluorescence were performed. After discontinuation of ambrisentan, the
      cotton wool spots resolved without recurrence. To the authors' knowledge, this is
      the first report of retinopathy in the form of cotton wool spots associated with
      the use of an endothelin receptor antagonist.

PMID- 24459201
TI  - From 'reckless' to 'mindful' in the use of outcome data to inform service-level
      performance management: perspectives from child mental health.

PMID- 24459202
TI  - Using balanced metrics and mixed methods to better understand QI interventions.

PMID- 24459203
TI  - Comparison of clinical outcome of pronation external rotation versus supination
      external rotation ankle fractures.
AB  - BACKGROUND: A pronation external rotation (PER) ankle fracture is a relatively
      uncommon injury. The purpose of this study was to examine the immediate and short
      term clinical outcomes of operatively treated PER IV ankle fractures and compare
      them with a similarly treated cohort of supination external rotation IV (SER IV)
      fractures. METHODS: 22 PER IV and 108 SER IV fractures were identified from a
      single surgeon's prospectively collected database from 2004 to 2010. All patients
      were treated with fracture fragment and ligament specific fixation during the
      same time period by the same surgeon. Postoperative radiographs and bilateral
      ankle computed tomography (CT) scans were reviewed for articular incongruity,
      syndesmotic malreduction, and loss of reduction. Clinical outcome measures,
      including the Foot and Ankle Outcome Score (FAOS) and ankle range of motion
      (ROM), were collected at latest follow-up visit. RESULTS: There was no difference
      in the rate of wound complications, fracture nonunion, or loss of reduction
      between the PER IV and SER IV groups. There was no significant difference in the
      incidence of postoperative articular incongruity (19% vs 8%, P = .23); however,
      the PER IV cohort was found to have a significantly higher rate of syndesmotic
      malreduction (40% vs 18%, P = .04). No clinically or statistically significant
      differences were detected between the 2 groups in regard to all FAOS domains.
      CONCLUSION: In a cohort of operatively treated PER IV fractures, fracture
      fragment and ligament specific fixation resulted in good short-term outcomes that
      were comparable to those seen in similarly treated patients with an SER IV
      fracture pattern. However, a notably greater number of syndesmotic malreductions
      were noted in the PER IV cohort, and therefore heightened scrutiny is recommended
      in treating this particular injury pattern. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 24459204
TI  - Treatment of naviculo-first cuneiform coalition of the foot.
AB  - BACKGROUND: Naviculo-first cuneiform coalition is a rare form of tarsal coalition
      with few reports. We therefore have analyzed its clinical features and the
      results of treatment. METHODS: We analyzed 36 feet in 28 patients diagnosed with
      naviculo-first cuneiform coalition from January 2003 to December 2010. The 28
      patients were 10 males and 18 females, with 18 right and 18 left feet, including
      8 patients with bilateral coalition. The location and morphological pattern of
      naviculo-first cuneiform coalition were analyzed radiologically. Symptomatic
      patients initially received conservative management for 6 months. Six feet of 5
      patients were treated operatively, 3 feet by curettage and 3 by fusion. RESULTS:
      Eighteen feet had symptoms, while 18 feet without symptoms were diagnosed
      incidentally. Mean patient age at diagnosis was 34.6 years (range, 10-68 years).
      The mean age at diagnosis of symptomatic patients was 29.6 years (range, 10-50
      years). Coalitions were located mainly in the medioplantar area. There was no
      bony coalition. Computed tomography or magnetic resonance imaging showed a cystic
      pattern in 7 patients, an irregular pattern in 4, a combined pattern in 5, and a
      spur-forming pattern in 1. The mean American Orthopaedic Foot & Ankle Society
      scores at the last follow-up in patients treated conservatively and operatively
      were 95.3 (range, 87-100) and 83.5 (range, 70-95), respectively. Among the 5
      operated patients, 3 patients (60%) complained of pain, including 2 who received
      curettage and 1 who developed a nonunion after attempted fusion. CONCLUSION:
      Conservative treatment should be considered over surgery in treating naviculo
      first cuneiform coalition. LEVEL OF EVIDENCE: Level III, comparative case series.

PMID- 24459206
TI  - Serum levels of insulin-like factor 3, anti-Mullerian hormone, inhibin B, and
      testosterone during pubertal transition in healthy boys: a longitudinal pilot
      study.
AB  - Insulin-like factor 3 (INSL3) is a promising marker of Leydig cell function with
      potentially high clinical relevance. Limited data of INSL3 levels in relation to
      other reproductive hormones in healthy pubertal boys exist. In this study, we
      aimed to evaluate longitudinal serum changes in INSL3 compared with LH, FSH,
      testosterone, inhibin B, and anti-Mullerian hormone (AMH) during puberty in
      healthy boys. Ten boys were included from the longitudinal part of the COPENHAGEN
      Puberty Study. Pubertal evaluation, including testicular volume, was performed
      and blood samples were drawn every 6 months for 5 years. Serum concentrations of
      testosterone were determined by a newly developed LC-MS/MS method, and serum
      concentrations of INSL3, AMH, inhibin B, FSH, and LH respectively were determined
      by validated immunoassays. The results showed that serum INSL3 levels increased
      progressively with increasing age, pubertal onset, and testicular volume. In six
      of the ten boys, LH increased before the first observed increase in INSL3. In the
      remaining four boys, the increase in LH and INSL3 was observed at the same
      examination. The increases in serum concentrations of LH, testosterone, and INSL3
      were not parallel or in ordered succession and varied interindividually. We
      demonstrated that INSL3 concentrations were tightly associated with pubertal
      onset and increasing testicular volume. However, the pubertal increases in LH,
      INSL3, and testosterone concentrations were not entirely parallel, suggesting
      that INSL3 and testosterone may be regulated differently. Thus, we speculate that
      INSL3 provides additional information on Leydig cell differentiation and function
      during puberty compared with traditional markers of testicular function. 

PMID- 24459207
TI  - Mitochondrial membrane potential in 2-cell stage embryos correlates with the
      success of preimplantation development.
AB  - Hormonal stimulation in superovulation induces female mice to ovulate more
      oocytes than spontaneous ovulation. Because the superovulated oocytes contain a
      number of oocytes that normally regress before spontaneous ovulation or immature
      oocytes, the development of some embryos that derive from these oocytes by IVF is
      prevented. Therefore, the quality of superovulated oocytes should differ from
      that of spontaneously ovulated oocytes. In this study, we evaluated the quality
      of superovulated oocytes, by examining 1- and 2-cell stage embryos, in which the
      development mainly depends on the maternal mRNA, proteins, and mitochondria that
      are contained in the oocytes, and we then measured the mitochondrial membrane
      potential (DeltaPsim) of the 1- and 2-cell stage, in vivo-fertilized, and IVF
      embryos. The DeltaPsim of 1-cell stage IVF embryos was lower than that of in vivo
      fertilized embryos; however, there was no difference between IVF embryos. During
      the developmental process from 1- to 2-cell stage, the DeltaPsim of in vivo
      fertilized embryos was highly upregulated, whereas a number of IVF embryos
      remained unchanged. As a result, 2-cell stage embryos were divided into two
      groups: high- and low- DeltaPsim 2-cell stage IVF embryos. The development of low
      DeltaPsim 2-cell stage IVF embryos tended to be arrested after the 2-cell stage.
      These results indicated that the upregulation of DeltaPsim during the 1- to 2
      cell stage was important in the development of early preimplantation embryos;
      there were some defects in the mitochondria of superovulated oocytes, which
      prevented their development. 

PMID- 24459205
TI  - An update on the biology of sphingosine 1-phosphate receptors.
AB  - Sphingosine 1-phosphate (S1P) is a membrane-derived lysophospholipid that acts
      primarily as an ex-tracellular signaling molecule. Signals initiated by S1P are
      transduced by five G protein-coupled receptors, named S1P1-5 Cellular and
      temporal expression of the S1P receptors (S1PRs) determine their specific roles
      in various organ systems, but they are particularly critical for regulation of
      the cardiovascular, immune, and nervous systems, with the most well-known
      contributions of S1PR signaling being modulation of vascular barrier function,
      vascular tone, and regulation of lymphocyte trafficking. However, our knowledge
      of S1PR biology is rapidly increasing as they become attractive therapeutic
      targets in several diseases, such as chronic inflammatory pathologies,
      autoimmunity, and cancer. Understanding how the S1PRs regulate interactions
      between biological systems will allow for greater efficacy in this novel
      therapeutic strategy as well as characterization of complex physiological
      networks. Because of the rapidly expanding body of research, this review will
      focus on the most recent advances in S1PRs. 

PMID- 24459209
TI  - Opportunity, Choice, and Burglary Victimization in Taiwan.
AB  - This study examined burglary victimization in Taiwan with an application of the
      structure-choice model that included four theoretical dimensions: proximity to
      crime, exposure to crime, target attractiveness, and guardianship. Drawing on the
      2000 Taiwan Areas Criminal Victimization Survey, the results of the current study
      showed a moderate effect of the opportunity model on Taiwan's burglary
      victimization. Also, this study found both consistent and conflicting findings in
      the current data. The null effect of motorcycles (including scooters) that
      represented the concept of target attractiveness in relation to burglary risk
      reflected a difference in population density and transportation needs between
      Taiwan and the West. Clearly, the role of social context needs to be understood
      when studies apply a Western model to a non-Western context. 

PMID- 24459208
TI  - Specific risk factors of arsonists in a forensic psychiatric hospital.
AB  - Arsonists are often treated in forensic settings. However, high recidivism rates
      indicate that treatment is not yet optimal for these offenders. The aim of this
      case series study is to identify arsonist specific dynamic risk factors that can
      be targeted during treatment. For this study, we used patient files of and
      interviews with all patients that were currently housed at a forensic psychiatric
      hospital in the Netherlands (14 arsonists, 59 non-arsonists). To delineate
      differences in risk factors between arsonists and non-arsonists, scores on the
      risk assessment instrument the Historical Clinical Future-30 (HKT-30; completed
      for 11 arsonists and 35 non-arsonists), an instrument similar to the Historical
      Clinical Risk Management-20 (HCR-20), were compared. The groups did not differ on
      demographic factors and psychopathology. Concerning dynamic risk factors,
      arsonists had significantly poorer social and relational skills and were more
      hostile. Although this study needs replication, these findings suggest that the
      treatment of people involved in firesetting should particularly target these risk
      factors. 

PMID- 24459210
TI  - Normal and aberrant splicing of LMNA.
AB  - The LMNA gene gives rise to at least three isoforms (lamin A, C, lamin ADelta10)
      as a result of normal alternative splicing, regulated by cis- and trans-acting
      regulatory factors, as well as the 5' and 3' untranslated regions of the gene.
      The two main isoforms, lamin A and C, are constitutive components of the fibrous
      nuclear lamina and have diverse physiological roles, ranging from mechanical
      nuclear membrane maintenance to gene regulation. The clinical spectrum of
      diseases (called 'laminopathies') caused by LMNA mutations is broad, including at
      least eight well-characterised phenotypes, some of which are confined to the
      skeletal muscles or skin, while others are multisystemic. This review discusses
      the different alternatively spliced isoforms of LMNA and the regulation of LMNA
      splicing, as well as the subgroup of mutations that affect splicing of LMNA pre
      mRNA, and also seeks to bridge the mis-splicing of LMNA at transcript level and
      the resulting clinical phenotypes. Finally, we discuss the manipulation of LMNA
      splicing by splice-switching antisense oligonucleotides and its therapeutic
      potential for the treatment of some laminopathies. 

PMID- 24459211
TI  - Next generation sequencing of chromosomal rearrangements in patients with split
      hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of
      DLX5/6 expression in humans.
AB  - OBJECTIVE: Split-hand/foot malformation type 1 is an autosomal dominant condition
      with reduced penetrance and variable expression. We report three individuals from
      two families with split-hand/split-foot malformation (SHFM) in whom next
      generation sequencing was performed to investigate the cause of their phenotype.
      METHODS AND RESULTS: The first proband has a de novo balanced translocation
      t(2;7)(p25.1;q22) identified by karyotyping. Whole genome sequencing showed that
      the chromosome 7 breakpoint is situated within the SHFM1 locus on chromosome
      7q21.3. This separates the DYNC1I1 exons recently identified as limb enhancers in
      mouse studies from their target genes, DLX5 and DLX6. In the second family, X
      linked recessive inheritance was suspected and exome sequencing was performed to
      search for a mutation in the affected proband and his uncle. No coding mutation
      was found within the SHFM2 locus at Xq26 or elsewhere in the exome, but a 106 kb
      deletion within the SHFM1 locus was detected through copy number analysis. Genome
      sequencing of the deletion breakpoints showed that the DLX5 and DLX6 genes are
      disomic but the putative DYNC1I1 exon 15 and 17 enhancers are deleted.
      CONCLUSIONS: Exome sequencing identified a 106 kb deletion that narrows the SHFM1
      critical region from 0.9 to 0.1 Mb and confirms a key role of DYNC1I1 exonic
      enhancers in normal limb formation in humans.

PMID- 24459212
TI  - Anomalous branch of pulmonary artery from the aorta and tetralogy of Fallot:
      morphology, surgical techniques and results.
AB  - OBJECTIVES: Tetralogy of Fallot (TOF) with hemitruncus (HT) is a rare entity. In
      this report, we present our experience with this condition over the last 20
      years. METHODS: Between January 1994 and June 2013, 11 patients with HT and TOF
      underwent surgery at the All India Institute of Medical Sciences, New Delhi,
      India. All available clinical, radiographic, echocardiographic, cardiac
      catheterization, operative and follow-up data were reviewed. RESULTS: The mean
      age was 73 +/- 7.1 months (range 7 months to 18 years) and the mean weight was
      15.7 +/- 1.2 kg. The mean preoperative saturation was 79.3 +/- 11.7% (range 62
      92%). Six patients had anomalous left pulmonary artery (PA), whereas 5 had an
      anomalous right PA arising from the aorta. Surgical procedures consisted of
      complete intracardiac repair of TOF with direct implantation of the anomalous PA
      into the main PA (n = 7), intracardiac repair of TOF with an interposition
      saphenous vein graft between the right PA and main PA (n = 1), and reconstruction
      of the left PA with autologous pericardium with intracardiac repair of TOF (n =
      1), direct implantation of the anomalous PA into the main PA with an innominate
      to right pulmonary artery shunt (n = 1) and a right PA banding with innominate to
      left PA shunt (n = 1). There were two early deaths. Follow-up ranged from 3 to 73
      months. All survivors are in NYHA Class I and follow-up echocardiograms did not
      show any residual lesions. CONCLUSIONS: Surgical repair of HT with TOF results in
      acceptable early outcomes. The surgical strategy needs to be individualized to
      the anatomy of the patient.

PMID- 24459213
TI  - Haemodynamic unloading increases the survival and affects the differentiation of
      cardiac stem cells after implantation into an infarcted heart.
AB  - OBJECTIVES: It has been anticipated that stem cell therapy is capable of
      repairing an injured heart but is currently limited by its marginal efficacy. We
      believe that mechanical stress due to haemodynamic loading may negate the
      therapeutic potency of stem cells and therefore investigated how haemodynamic
      unloading affects the survival and differentiation of stem cells after
      implantation into an infarcted heart. METHODS: A left ventricular (LV)
      haemodynamic unloading model was implemented by heterotopic transplantation of an
      infarcted donor heart into another healthy mouse. An in situ infarcted heart with
      general haemodynamic loading was used as control. A total of 5 million cardiac
      stem cells expanded from green fluorescence protein (GFP)-transgenic mouse were
      intramyocardially implanted into the infarcted LVs of haemodynamically unloaded
      donor heart or general haemodynamic loaded heart. The survival and
      differentiation of the implanted cardiac stem cells were evaluated by
      histological analyses at 3 and 21 days after cell implantation (n = 5-6 in each
      time points per group). RESULTS: Compared with the general haemodynamic loading
      condition, haemodynamic unloading of the infarcted hearts significantly improved
      the survival, increased the proliferation and inhibited the apoptosis of cardiac
      stem cells at 21 days after cell implantation (P < 0.05). In addition, the number
      of GFP(+)/Sca-1(+) cells was much higher in the unloaded hearts than in the
      loaded hearts at 21 days after cell implantation, although the difference was not
      statistically significant (5.67 +/- 5.10 vs 0.75 +/- 0.50, P = 0.051). Among the
      surviving GFP(+) donor cells 21 days after implantation, the expressions of
      platelet endothelial cell adhesion molecule-1, smooth muscle actin and sarcomeric
      alpha actin were ~7, 38 and 27% in the loaded heart and ~19, 14 and 55% in the
      unloaded heart, respectively. CONCLUSIONS: Haemodynamic unloading favours the
      survival/engraftment of donor stem cells and affects their differentiation after
      implantation into an infarcted heart. Although further studies in a large animal
      model are required to investigate the functional benefits of haemodynamic
      unloading on stem cell therapy, we may temporarily unload the damaged heart to
      enhance cell engraftment and then load the heart again to induce the
      differentiation of stem cells.

PMID- 24459214
TI  - Thymoma with intravascular extension into the right atrium.

PMID- 24459215
TI  - Thymoma and inter-relationships between clinical variables: a multicentre study
      in 537 patients.
AB  - OBJECTIVES: In thymomas, the roles of Masaoka-Koga stage, histology and the
      presence of myasthenia gravis (MG) have been considered fundamental for patient
      management and outcomes. In this study, we retrospectively evaluated several
      clinical variables, with the aim of outlining their relationships and
      clinical/prognostic significance in resected thymoma patients. METHODS: A
      retrospective search of our surgical database for patients operated on for
      thymoma in six Italian high-volume thoracic surgery centres between 2000 and 2011
      was conducted. The following clinical variables were evaluated: Masaoka-Koga
      Stage, tumour histology, the presence of MG, other autoimmune syndromes or second
      tumours, the completeness of tumour resection and the development of recurrences.
      RESULTS: Five hundred and thirty-seven (273 males-51%) were retrospectively
      included in this study. Our results indicate that: (i) MG correlates with early
      Masaoka-Koga stage and B-type thymoma; (ii) Stage III-IVa tumours correlate with
      B-type tumour; (iii) autoimmune paraneoplastic syndromes correlate with Stage I
      II thymoma; (iv) second malignancies correlate with the absence of paraneoplastic
      disorders and weakly with B-type tumour and (v) overall survival was influenced
      by Masaoka-Koga stage and completeness of surgical resection. CONCLUSIONS: In
      thymomas, Masaoka-Koga stage, histology, MG, other autoimmune syndromes and
      second malignancies are inter-related, but only Masaoka-Koga tumour stage, amid
      these clinical variables, has been demonstrated to be a strong prognostic
      indicator of survival.

PMID- 24459216
TI  - Aortic dissection extending through a patent ductus arteriosus device.

PMID- 24459217
TI  - Use of free subcutaneous fat pad for reduction of intraoperative air leak in
      thoracoscopic pulmonary resection cases with lung cancer.
AB  - Intraoperative alveolar air leaks occur in patients with non-small-cell lung
      cancer (NSCLC) following a pulmonary resection using thoracoscopic surgery. We
      showed the efficacy of covering damaged lung tissue with a subcutaneous fat pad
      for preventing postoperative air leak. Thoracoscopic surgery was performed for
      NSCLC patients with three incisions along with a 3-4 cm anterior utility
      incision. When an air leak originated from deep within the pulmonary parenchyma
      or was large, a subcutaneous fat pad ~2 * 2 cm in size was harvested from the
      utility incision and placed on the damaged lung tissue with fibrin glue and 2-3
      mattress sutures. Subcutaneous fat pads were used for 50 patients with NSCLC
      during thoracoscopic surgery procedures. There were no intraoperative
      complications in any of the patients. A prolonged air leak (>7 days) was noted in
      3 (6%) of the 50 patients. Air leak was diminished at 1.5 +/- 2.6 postoperative
      days and the chest tubes removed at 3.2 +/- 2.8 postoperative days. Reinforcement
      of damaged lung tissues by use of subcutaneous free fat pads is a safe and
      intriguing procedure in NSCLC patients who underwent a pulmonary resection in
      thoracoscopic surgery. 

PMID- 24459218
TI  - Quantifying disease involvement in Takayasu's arteritis.

PMID- 24459219
TI  - Autologous stem cell transplantation with thiotepa-based conditioning in patients
      with systemic sclerosis and cardiac manifestations.
AB  - OBJECTIVE: The aim of this study was to find a new and less cardiotoxic
      conditioning regimen for high-dose chemotherapy and autologous stem cell
      transplantation (aSCT) in patients with severe SSc and pre-existing cardiac
      involvement. METHODS: Six patients with cardiac involvement were treated for SSc
      with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic
      alkylant thiotepa. All patients received an implantable cardioverter
      defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured
      according to reduction of the modified Rodnan skin score (mRSS). CT histography
      was used to monitor pulmonary manifestations, as were echocardiography, N
      terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac
      involvement. Cardiac events were defined as death or hospitalisation due to heart
      failure or appropriate discharge of the ICD. RESULTS: Between December 2008 and
      May 2012, four male and two female patients with a median age of 41 years
      received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5
      at month 6 and 12, respectively. The total lung volume also significantly
      improved. Within the median follow-up of 1.6 years (range 1-3.8) two patients
      experienced a relapse of SSc, which results in a progression-free survival rate
      of 66.6%. Three patients experienced ICD discharge. CONCLUSION: For patients with
      SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible
      and effective. The rate of ICD discharge underlines the need for protection in
      these endangered patients. This preliminary experience allowed us to use this
      regimen for our currently recruiting prospective trial (NCT01895244).

PMID- 24459221
TI  - Changes in physical activity measured by accelerometry following initiation of
      DMARD therapy in rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to assess changes in habitual physical
      activity levels in response to DMARD therapy in RA patients. METHODS: Eighteen
      drug-naive RA patients were prospectively assessed at baseline and following 3
      months of DMARD therapy for habitual physical activity by accelerometry, disease
      activity using the clinical disease activity index (CDAI) and functional
      disability using the modified HAQ (mHAQ). Baseline physical activity was also
      compared with an equal number of healthy control participants matched for age,
      sex and BMI. RESULTS: Following 3 months of DMARD therapy, in parallel with
      significant improvements in CDAI scores (P < 0.001) and HAQ scores (P < 0.001),
      accelerometry measures in the RA cohort showed that the average activity counts
      in sedentary thresholds decreased (P = 0.012), while average activity counts
      within higher-intensity thresholds increased (P = 0.039). Multiple regression
      analysis showed that the change in moderate activity was associated with a
      decrease in CRP (beta = - 0.922, P = 0.026) while the decrease in sedentary
      activity and increase in moderate activity were associated with decreased morning
      stiffness of the joints (beta = 0.694, P = 0.035 and beta = -0.927, P = 0.024,
      respectively). At baseline, RA patients were less physically active than control
      participants in the morning (P = 0.048) and in the late afternoon (P = 0.016),
      but these diurnal differences were no longer significant after the DMARD
      intervention. CONCLUSION: These findings suggest that accelerometry may
      potentially be a viable objective method of assessing changes in physical
      disability in response to various disease-modifying drugs.

PMID- 24459220
TI  - Predictors of pain medication use for arthroplasty pain after revision total knee
      arthroplasty.
AB  - OBJECTIVE: Our objective was to study the use of pain medications for persistent
      knee pain and their predictors after revision total knee arthroplasty (TKA).
      METHODS: We examined whether demographic (gender, age) and clinical
      characteristics [BMI, co-morbidity measured by the Deyo-Charlson index (a 5-point
      increase), anxiety and depression] predict the use of NSAIDs and narcotic pain
      medications 2 and 5 years after revision TKA. Multivariable logistic regression
      adjusted for these predictors as well as operative diagnosis, American Society of
      Anesthesiologists class and distance from the medical centre. RESULTS: A total of
      1533 patients responded to the 2-year questionnaire and 881 responded to the 5
      year questionnaire. NSAID use was reported by 13.4% (206/1533) of patients at 2
      years and 16.7% (147/881) at 5 years. Narcotic medication use was reported by
      5.4% (83/1533) of patients at 2 years and 5.9% (52/881) at 5 years. Significant
      predictors of the use of NSAIDs for index TKA pain at 2 and 5 years were age >60
      70 years [odds ratio (OR) 0.62 (95% CI 0.39, 0.98) and 0.46 (0.25, 0.85)]
      compared with age <=60 years and a higher Deyo-Charlson index [OR 0.51 (95% CI
      0.28, 0.93)] per 5-point increase at 5-year after revision TKA. Significant
      predictors of narcotic pain medication use for index TKA pain were age >60-70
      years [OR 0.41 (0.21, 0.78)] and >70-80 years [0.40 (95% CI 0.22, 0.73)] at 2
      years and depression [OR 4.58 (95% CI 1.58, 13.18)] at 5 years. CONCLUSION:
      Younger age and depression were risk factors for the use of NSAIDs and narcotic
      pain medications for index TKA pain at 2- and 5-years after revision TKA.

PMID- 24459222
TI  - Hybrid surgery for dural arteriovenous fistula in the neurosurgical hybrid
      operating suite.
AB  - Treatment of a dural arteriovenous fistula (AVF), which is difficult to access by
      either the surgical or endovascular approach, is challenging. A hybrid technique,
      combining a microsurgical approach and endovascular embolization, can provide
      less invasive management of dural AVFs in a modern neurosurgical hybrid operating
      suite. We present a case of intracerebral hemorrhage in the left cerebellum
      secondary to dural AVF, Cognard type IV with numerous tiny feeders from the
      ascending pharyngeal artery branches. No adequate arterial or venous route for
      endovascular embolization was found by neuroangiography. The hybrid technique,
      combining keyhole pterional craniotomy and embolization with n-butyl
      cyanoacrylate glue injection via direct cannulation of the periclival venous
      plexus, succeeded in obliterating the dural AVF. Intraoperative angiography
      showed successful embolization of the dural AVF without any complication. This
      report illustrates the usefulness of the neurosurgical hybrid operating suite for
      the treatment of difficult dural AVFs. 

PMID- 24459223
TI  - Bizarre parosteal osteochondromatous proliferation (Nora's lesion) of phalanx in
      a child.
AB  - Bizarre parosteal osteochondromatous proliferation (BPOP; also called Nora's
      lesion) is a benign surface osteocartilaginous lesion, which is infrequently
      reported in world literature. The condition is classically described in the short
      tubular bones of hands and feet in the second and third decades of life. We
      present a case report of BPOP of the middle phalanx of middle finger in a 4-year
      old girl. The child underwent a wide excision and remained asymptomatic at 2.5
      years of follow-up. Our case report highlights the importance of suspecting
      Nora's lesion in a child. It also helps in delineating a differential diagnosis
      and discusses the management principles of this rare osteocartilaginous lesion. 

PMID- 24459224
TI  - Undiagnosed intussusception in an adult 'small and large bowel'.
AB  - Two cases of adult intussusception (large bowel and small bowel) are presented
      highlighting the challenges posed by their often innocuous presentation in
      addition to significant morbidity resulting from delayed diagnosis. 

PMID- 24459225
TI  - Delayed compartment syndrome of leg and foot due to rupture of popliteal artery
      pseudoaneurysm following posterior cruciate ligament reconstruction.
AB  - Arthroscopic posterior cruciate ligament (PCL) reconstruction carries some risk
      of complications, including injury to the neurovascular structures at the
      popliteal region. We describe a delayed presentation of the right leg and foot
      compartment syndrome following rupture of popliteal artery pseudoaneurysm, which
      presented 9 days after an arthroscopic transtibial PCL reconstructive surgery.
      Fasciotomy, surgical exploration, repair of an injured popliteal vein and
      revascularisation of the popliteal artery with autogenous great saphenous vein
      interposition graft were performed. Owing to the close proximity of vessels to
      the tibial tunnel, special care should be taken in patients who undergo
      arthroscopic PCL reconstruction, especially if there is extensive scarring of the
      posterior capsule following previous injury. Emergency fasciotomy should not be
      delayed and is justified when the diagnosis of compartment syndrome is clinically
      made. 

PMID- 24459226
TI  - Caecal volvulus following abdominoplasty: a tale of caution.
AB  - We present a case of a 30-year-old woman with a gangrenous right colon secondary
      to caecal volvulus, diagnosed postabdominoplasty. To our knowledge, this is the
      first case recorded in the literature. An emergency right hemicolectomy was
      performed and the patient had an unremarkable recovery. Given the severity of
      this incident, the diagnosis of caecal volvulus postabdominoplasty requires a
      high index of suspicion to allow prompt diagnosis and treatment. 

PMID- 24459227
TI  - Frontoethmoidal mucocele presenting as proptosis.

PMID- 24459228
TI  - Siderosis bulbi as a consequence of a missed intraocular foreign body.
AB  - We present a case of a 56-year-old man who suffered an injury to his right eye in
      June 2012. He presented to an emergency department, however, the presence of a
      penetrating injury and an intraocular foreign body was not identified. A year
      later he was referred to the ophthalmology department due to reduced vision and
      change of iris colour in the same eye. Examination revealed clinical signs
      consistent with a previous penetrating injury and a retained ferrous intraocular
      foreign body. 

PMID- 24459229
TI  - Rituximab treatment prevents the early development of proteinuria following pig
      to-baboon xeno-kidney transplantation.
AB  - We previously reported life-supporting alpha1,3-galactosyltransferase knockout
      (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite
      otherwise normal renal function, recipients developed proteinuria with
      morphologic changes (podocyte effacement), a condition that presents a major
      obstacle to long-term studies in this model. A recent clinical study showed that
      rituximab therapy after allogeneic transplant prevented proteinuria possibly
      associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b).
      Here, we demonstrate that rituximab prevents the disruption of pig podocytes in
      an SMPDL-3b-dependent manner in vitro and the early development of proteinuria
      after xenogeneic kidney transplantation in baboons. Immunofluorescence showed
      SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation
      demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig
      podocytes with naive baboon sera, which has preformed antipig natural antibodies,
      reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased
      podocyte proliferation, whereas pretreatment with rituximab prevented these
      effects. Six baboons received rituximab before transplantation to deplete B cells
      and again in the peri-transplant period; 18 baboons treated only before
      transplantation served as historical controls. The onset of post-transplant
      proteinuria was significantly delayed in a B cell-independent manner in the
      animals that received peri-transplant rituximab treatment. Although further
      optimization of this protocol is required, these data provide intriguing clues to
      the mechanisms of post-transplant proteinuria in xenogeneic kidney
      transplantation and a potential strategy for its prevention. 

PMID- 24459230
TI  - Rituximab: a boot to protect the foot.

PMID- 24459231
TI  - Sickle trait in African-American hemodialysis patients and higher erythropoiesis
      stimulating agent dose.
AB  - African Americans require higher doses of erythropoiesis-stimulating agents
      (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait
      and other hemoglobinopathy traits on anemia in dialysis patients has not been
      adequately evaluated. We performed a cross-sectional study of a large cohort of
      adult African-American hemodialysis patients in the United States to determine
      the prevalence of hemoglobinopathy traits and quantify their influence on ESA
      dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among
      5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and
      129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were
      present. Sickle cell trait was more common in this cohort than the general
      African-American population (10.2% versus 6.5%-8.7%, respectively, P<0.05). Among
      5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving
      ESAs, demographic and clinical variables were similar across groups, with
      achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy
      traits received higher median doses of ESA than patients with normal hemoglobin
      (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable
      analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment
      (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003)
      higher dose and hemoglobin C trait patients exhibited a similar difference
      (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and
      separate logistic regression models showed comparable associations. Our findings
      suggest that the presence of sickle cell trait and hemoglobin C trait may
      explain, at least in part, prior observations of greater ESA doses administered
      to African-American dialysis patients relative to Caucasian patients. 

PMID- 24459232
TI  - Adenine phosphoribosyltransferase deficiency as a rare cause of renal allograft
      dysfunction.
AB  - Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive
      disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the
      generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in
      urine, yielding kidney injury and in some patients, kidney failure. Early
      recognition of the disease, institution of xanthine analog therapy to block the
      formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent
      CKD. Because of symptom variability and lack of awareness, however, the diagnosis
      is sometimes extremely deferred. We describe a patient with adenine
      phosphoribosyltransferase deficiency who was diagnosed during evaluation of a
      poorly functioning second kidney allograft. This report highlights the risk of
      renal allograft loss in patients with undiagnosed adenine
      phosphoribosyltransferase deficiency and the need for improved early detection of
      this disease. 

PMID- 24459234
TI  - Notice of retractions.

PMID- 24459233
TI  - IL-22 ameliorates renal ischemia-reperfusion injury by targeting proximal tubule
      epithelium.
AB  - IL-22 is an epithelial cell survival cytokine that is currently under development
      for the treatment of acute liver damage. Here, we used a mouse model of renal
      ischemia/reperfusion (I/R) injury to investigate whether IL-22 has therapeutic
      potential for the treatment of AKI. The action of IL-22 is mediated by binding to
      IL-22R1 and leads to STAT3 activation. Under physiologic conditions, renal
      expression of IL-22R1 was detected only in the brush border of the renal proximal
      tubular epithelial cells (RPTECs). Renal I/R elevated serum IL-22 levels slightly
      but did not induce STAT3 phosphorylation in RPTECs. IL-22-deficient mice had
      slightly increased I/R-induced injury compared with wild-type mice. In contrast,
      treatment with IL-22 or overexpression of IL-22 by either gene targeting (IL-22
      transgenic mice) or administration of adenovirus expressing IL-22 increased STAT3
      phosphorylation in RPTECs, ameliorated I/R-induced renal inflammation and tubular
      cell injury, and preserved renal functions. Overexpression of IL-22 increased the
      phosphorylation of STAT3 and Akt, upregulated antiapoptotic genes (e.g., Bcl-2),
      and downregulated proapoptotic genes (e.g., Bad) in the kidneys of mice subjected
      to I/R. Notably, phosphorylation of Akt increased and expression of Bad decreased
      in proximal tubular cells under these conditions. Furthermore, compared with wild
      type mice, IL-22 transgenic mice had increased survival rates, whereas IL-22
      deficient mice had reduced survival rates after I/R injury. In summary, renal
      expression of IL-22R1 is restricted to RPTECs, and treatment with IL-22 protects
      against renal I/R injury by activating STAT3 and AKT, suggesting that IL-22 has
      therapeutic potential for the treatment of AKI.

PMID- 24459236
TI  - Management of endocrine disease: a clinical update on tumor-induced hypoglycemia.
AB  - Tumor-induced hypoglycemia (TIH) is a rare clinical entity that may occur in
      patients with diverse kinds of tumor lineages and that may be caused by different
      mechanisms. These pathogenic mechanisms include the eutopic insulin secretion by
      a pancreatic islet beta-cell tumor, and also the ectopic tumor insulin secretion
      by non-islet-cell tumor, such as bronchial carcinoids and gastrointestinal
      stromal tumors. Insulinoma is, by far, the most common tumor associated with
      clinical and biochemical hypoglycemia. Insulinomas are usually single, small,
      sporadic, and intrapancreatic benign tumors. Only 5-10% of insulinomas are
      malignant. Insulinoma may be associated with the multiple endocrine neoplasia
      type 1 in 4-6% of patients. Medical therapy with diazoxide or somatostatin
      analogs has been used to control hypoglycemic symptoms in patients with
      insulinoma, but only surgical excision by enucleation or partial pancreatectomy
      is curative. Other mechanisms that may, more uncommonly, account for tumor
      associated hypoglycemia without excess insulin secretion are the tumor secretion
      of peptides capable of causing glucose consumption by different mechanisms. These
      are the cases of tumors producing IGF2 precursors, IGF1, somatostatin, and
      glucagon-like peptide 1. Tumor autoimmune hypoglycemia occurs due to the
      production of insulin by tumor cells or insulin receptor autoantibodies. Lastly,
      massive tumor burden with glucose consumption, massive tumor liver infiltration,
      and pituitary or adrenal glands destruction by tumor are other mechanisms for TIH
      in cases of large and aggressive neoplasias. 

PMID- 24459235
TI  - Toll-like receptor 4-induced IL-22 accelerates kidney regeneration.
AB  - AKI involves early Toll-like receptor (TLR)-driven immunopathology, and
      resolution of inflammation is needed for rapid regeneration of injured tubule
      cells. Notably, activation of TLRs also has been implicated in epithelial repair.
      We hypothesized that TLR signaling drives tubule regeneration after acute injury
      through the induction of certain ILs. Systematic screening in vitro identified IL
      22 as a candidate proregeneratory factor in primary tubular cell recovery, and IL
      22 deficiency or IL-22 blockade impaired post-ischemic tubular recovery after AKI
      in mice. Interstitial mononuclear cells, such as dendritic cells and macrophages,
      were the predominant source of IL-22 secretion, whereas IL-22 receptor was
      expressed by tubular epithelial cells exclusively. Depleting IL-22-producing
      cells during the healing phase impaired epithelial recovery, which could be
      rescued entirely by reconstituting mice with IL-22. In vitro, necrotic tubular
      cells and oxidative stress induced IL-22 secretion selectively through TLR4.
      Although TLR4 blockade during the early injury phase prevented tubular necrosis
      and AKI, TLR4 blockade during the healing phase suppressed IL-22 production and
      impaired kidney regeneration. Taken together, these results suggest that necrotic
      cell-derived TLR4 agonists activate intrarenal mononuclear cells to secrete IL
      22, which accelerates tubular regeneration and recovery in AKI.

PMID- 24459237
TI  - Evaluation of right adrenal vein cannulation by computed tomography angiography
      in 140 consecutive patients undergoing adrenal venous sampling.
AB  - OBJECTIVE: As it is now known that primary aldosteronism (PA) is more prevalent
      than was previously recognized, and is a potentially curable cause of
      hypertension and related cardiovascular diseases, the search for a safe and
      effective means of its diagnosis has reemerged as a topic of interest. Adrenal
      venous sampling is the gold standard for diagnosis of PA, but the technique is
      challenging and the small right adrenal vein can be particularly difficult to
      cannulate. Our objective was to evaluate the usefulness of computed tomography
      during angiography (angio-CT) in increasing the success of adrenal venous
      sampling and to identify factors associated with cannulation failure. DESIGN:
      Retrospective review. METHODS: A total of 140 consecutive patients with suspected
      PA except Cushing's syndrome treated at a single hospital from June 2008 to May
      2013 were included. Catheter misplacement and correct cannulation rates before
      angio-CT and success rate of sampling after angio-CT were calculated. Univariate
      analysis for factors related to incorrect cannulation included gender, age,
      height, weight, BMI, and adrenal nodules. Successful sampling was biochemically
      defined according to cortisol concentrations in the venous blood samples.
      RESULTS: Angio-CT detected misplaced catheters in 13 patients (9.3%). The
      calculated correct cannulation rate of adrenal vein sampling increased from 86.4%
      before angio-CT to 95.7% after CT (P<0.001, McNemar's test). Univariate analysis
      showed a tendency for a higher rate of failure of right adrenal venous sampling
      in taller patients (P=0.052, Mann-Whitney's U test). CONCLUSION: Angio-CT
      improved success of adrenal venous sampling.

PMID- 24459238
TI  - Diagnosis of endocrine disease: thyroid ultrasound (US) and US-assisted
      procedures: from the shadows into an array of applications.
AB  - In patients with thyroid nodules, ultrasound (US) imaging represents an
      indispensable tool for assessment of the risk of malignancy. Over approximately
      four decades, innovative technology and successive improvements have facilitated
      its entry into the routine management and greatly improved its predictive value.
      When US features cannot reliably rule out thyroid cancer, US guidance allows a
      correct and safe sampling also of small or deeply located thyroid lesions.
      Obtained in this way, cytological or microhistological specimens may reliably
      define the nature of most thyroid nodules, and the information from histochemical
      or molecular markers shows promise in the classification of the remaining
      indeterminate cases. While a prompt surgical treatment can be offered in the
      minority of suspicious or definitely malignant cases, most individuals warrant
      only a follow-up. However, at initial evaluation, or over the years, a fraction
      of these benign lesions may grow and/or become symptomatic. Such cases may
      benefit from US-guided minimally invasive procedures as an alternative to
      surgery. Image-guided percutaneous treatments most often achieve relief of neck
      complaints, are inexpensive, and can be performed on an outpatient basis. The
      risk of major complications, after adequate training, is very low. Importantly,
      thyroid function is preserved. Currently, percutaneous ethanol injection for
      cystic lesions and thermal ablation, with laser or radiofrequency, for solid
      nodules are increasingly used and disseminated beyond the initial core
      facilities. In centres with expertise and high patient volume, their use should
      be considered as first-line treatment alternatives to surgery for selected
      patients with benign enlarging or symptomatic thyroid lesions. 

PMID- 24459239
TI  - Martin P. Levin Mentorship Award--thoughts on mentoring.

PMID- 24459241
TI  - Multimodality imaging of mid-ventricular obstruction in left ventricular
      noncompaction.

PMID- 24459240
TI  - An intervention based on Schachter's externality theory for overweight children:
      the regulation of cues pilot.
AB  - OBJECTIVE: This study evaluated the feasibility, acceptability, and initial
      efficacy of an intervention based on Schachter's externality theory; the
      Regulation of Cues (ROC) program. METHODS: 44 overweight and obese 8-12-year-old
      children and their parents were randomly assigned to a 4-month ROC program or the
      control group. Outcomes were assessed at baseline, posttreatment, and 4 months
      posttreatment and included acceptability and feasibility, body weight, and eating
      behaviors. RESULTS: The ROC program had moderate to high acceptability ratings.
      Significant improvements were found for the ROC group compared with the control
      group on child food responsiveness at posttreatment and eating in the absence of
      hunger at 4 months posttreatment. Improvements were seen for the ROC group
      compared with the control group on body weight measures and food responsiveness,
      although these only approached significance. CONCLUSION: The ROC intervention may
      be useful with overweight and obese children. Larger, fully powered studies are
      needed to further evaluate the efficacy of this model.

PMID- 24459242
TI  - Major congenital coronary artery anomalies in a paediatric and adult population:
      a prospective echocardiographic study.
AB  - AIMS: We sought to describe our experience with major coronary anomalies (MCAs)
      diagnosed in transthoracic echocardiography (TTE) in a large adult and paediatric
      population. MCAs may have serious clinical consequences. No echocardiographic
      studies have prospectively screened MCA in a general adult and paediatric
      population. METHODS AND RESULTS: From June 2008 to January 2012, a systematic
      search for MCA was prospectively conducted in children and adult patients, coming
      for a TTE. Three thousand five hundred and two patients (84% adults and 16%
      children) underwent a TTE. Fourteen coronary anomalies (0.39%) were diagnosed:
      nine anomalous origins of coronary artery from the opposite sinus with inter
      arterial course, one abnormal left coronary artery from the pulmonary artery,
      three single coronary ostia, and one coronary fistula. Cardiac symptoms initiated
      investigation in seven patients. Five patients underwent specific surgery: two
      coronary reimplantations and three coronary bypass grafting. Ten patients had
      already undergone at least one TTE with the anomalous coronary artery being
      neither diagnosed nor suspected. CONCLUSIONS: MCA is a rare condition. TTE
      appears to be a potentially useful modality for the initial screening of MCA in
      adults and children, provided special attention is paid to coronary artery
      analysis.

PMID- 24459243
TI  - Reporting standards in cardiac MRI, CT, and SPECT diagnostic accuracy studies:
      analysis of the impact of STARD criteria.
AB  - AIMS: Diagnostic accuracy studies determine the clinical value of non-invasive
      cardiac imaging tests. The 'STAndards for the Reporting of Diagnostic accuracy
      studies' (STARD) were published in 2003 to improve the quality of study
      reporting. We aimed to assess the reporting quality of cardiac computed
      tomography (CCT), single positron emission computed tomography (SPECT), and
      cardiac magnetic resonance (CMR) diagnostic accuracy studies; to evaluate the
      impact of STARD; and to investigate the relationships between reporting quality,
      journal impact factor, and study citation index. METHODS AND RESULTS: We randomly
      generated six groups of 50 diagnostic accuracy studies: 'CMR 1995-2002', 'CMR
      2004-11', 'CCT 1995-2002', 'CCT 2004-11', 'SPECT 1995-2002', and 'SPECT 2004-11'.
      The 300 studies were double-read by two blinded reviewers and reporting quality
      determined by % adherence to the 25 STARD criteria. Reporting quality increased
      from 65.3% before STARD to 74.1% after (P = 0.003) in CMR studies and from 61.6
      to 79.0% (P < 0.001) in CCT studies. SPECT studies showed no significant change:
      71.9% before and 71.5% after STARD (P = 0.92). Journals advising authors to refer
      to STARD had significantly higher impact factors than those that did not (P =
      0.03), and journals with above-median impact factors published studies of
      significantly higher reporting quality (P < 0.001). Since STARD, citation index
      has not significantly increased (P = 0.14), but, after adjustment for impact
      factor, reporting quality continues to increase by ~1.5% each year. CONCLUSION:
      Reporting standards for diagnostic accuracy studies of non-invasive cardiac
      imaging are at most satisfactory and have improved since the introduction of
      STARD. Adherence to STARD should be mandatory for authors of diagnostic accuracy
      studies.

PMID- 24459244
TI  - Morphine glucuronidation and glucosidation represent complementary metabolic
      pathways that are both catalyzed by UDP-glucuronosyltransferase 2B7: kinetic,
      inhibition, and molecular modeling studies.
AB  - Morphine 3-beta-D-glucuronide (M3G) and morphine 6-beta-D-glucuronide (M6G) are
      the major metabolites of morphine in humans. More recently, morphine-3-beta-d
      glucoside (M-3-glucoside) was identified in the urine of patients treated with
      morphine. Kinetic and inhibition studies using human liver microsomes (HLM) and
      recombinant UGTs as enzyme sources along with molecular modeling were used here
      to characterize the relationship between morphine glucuronidation and
      glucosidation. The M3G to M6G intrinsic clearance (C(Lint)) ratio (~5.5) from HLM
      supplemented with UDP-glucuronic acid (UDP-GlcUA) alone was consistent with the
      relative formation of these metabolites in humans. The mean C(Lint) values
      observed for M-3-glucoside by incubations of HLM with UDP-glucose (UDP-Glc) as
      cofactor were approximately twice those for M6G formation. However, although the
      M3G-to-M6G C(Lint) ratio remained close to 5.5 when human liver microsomal
      kinetic studies were performed in the presence of a 1:1 mixture of cofactors, the
      mean C(Lint) value for M-3-glucoside formation was less than that of M6G. Studies
      with UGT enzyme-selective inhibitors and recombinant UGT enzymes, along with
      effects of BSA on morphine glycosidation kinetics, were consistent with a major
      role of UGT2B7 in both morphine glucuronidation and glucosidation. Molecular
      modeling identified key amino acids involved in the binding of UDP-GlcUA and UDP
      Glc to UGT2B7. Mutagenesis of these residues abolished morphine glucuronidation
      and glucosidation. Overall, the data indicate that morphine glucuronidation and
      glucosidation occur as complementary metabolic pathways catalyzed by a common
      enzyme (UGT2B7). Glucuronidation is the dominant metabolic pathway because the
      binding affinity of UDP-GlcUA to UGT2B7 is higher than that of UDP-Glc.

PMID- 24459246
TI  - Role of family and carers in compulsory mental health treatment.

PMID- 24459245
TI  - BK channel-mediated relaxation of urinary bladder smooth muscle: a novel paradigm
      for phosphodiesterase type 4 regulation of bladder function.
AB  - Elevation of intracellular cAMP and activation of protein kinase A (PKA) lead to
      activation of large conductance voltage- and Ca(2+)-activated K(+) (BK) channels,
      thus attenuation of detrusor smooth muscle (DSM) contractility. In this study, we
      investigated the mechanism by which pharmacological inhibition of cAMP-specific
      phosphodiesterase 4 (PDE4) with rolipram or Ro-20-1724 (C(15)H(22)N(2)O(3))
      suppresses guinea pig DSM excitability and contractility. We used high-speed line
      scanning confocal microscopy, ratiometric fluorescence Ca(2+) imaging, and
      perforated whole-cell patch-clamp techniques on freshly isolated DSM cells, along
      with isometric tension recordings of DSM isolated strips. Rolipram caused an
      increase in the frequency of Ca(2+) sparks and the spontaneous transient BK
      currents (TBKCs), hyperpolarized the cell membrane potential (MP), and decreased
      the intracellular Ca(2+) levels. Blocking BK channels with paxilline reversed the
      hyperpolarizing effect of rolipram and depolarized the MP back to the control
      levels. In the presence of H-89 [N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]
      5-isoquinolinesulfonamide dihydrochloride], a PKA inhibitor, rolipram did not
      cause MP hyperpolarization. Rolipram or Ro-20-1724 reduced DSM spontaneous and
      carbachol-induced phasic contraction amplitude, muscle force, duration, and
      frequency, and electrical field stimulation-induced contraction amplitude, muscle
      force, and tone. Paxilline recovered DSM contractility, which was suppressed by
      pretreatment with PDE4 inhibitors. Rolipram had reduced inhibitory effects on DSM
      contractility in DSM strips pretreated with paxilline. This study revealed a
      novel cellular mechanism whereby pharmacological inhibition of PDE4 leads to
      suppression of guinea pig DSM contractility by increasing the frequency of Ca(2+)
      sparks and the functionally coupled TBKCs, consequently hyperpolarizing DSM cell
      MP. Collectively, this decreases the global intracellular Ca(2+) levels and DSM
      contractility in a BK channel-dependent manner.

PMID- 24459247
TI  - Side effects could certainly be decreased with lower dose of quinidine in
      asymptomatic Brugada patients, but what about efficacy? Author reply.

PMID- 24459248
TI  - Adverse effects of long-term therapeutic doses of quinidine in asymptomatic
      Brugada patients: should low doses be used first?

PMID- 24459249
TI  - Lipoma arborescens in the extensor tendon sheath of the hand secondary to foreign
      body reaction.

PMID- 24459250
TI  - 'An hairy palm': a pilonidal sinus in a Dupuytren's pit.

PMID- 24459251
TI  - Ten year follow-up of pyrocarbon implants for proximal interphalangeal joint
      replacement.
AB  - Results of anatomical resurfacing of the proximal interphalangeal joint using
      pyrocarbon implants showed reasonable clinical results with a high radiographic
      migration rate. The aim was to investigate the subjective, clinical, and
      radiographic results 10 years following surgery, and to compare them with our 2
      year follow-up data. We re-evaluated 12 patients with 15 proximal interphalangeal
      implants on average 9.7 years after surgery. Pain significantly improved from 7.6
      on a visual analogue scale pre-operatively to 1.4 at 2 years, and to 0.7 at the
      final follow-up. The mean total range of motion in all replaced joints was 36
      degrees  pre-operatively and 39 degrees  at the 2-year follow-up, but had
      decreased significantly to 29 degrees  at 10 years. We saw one implant migration
      in addition to the eight migrated implants we already found 2 years after
      surgery. The moderate clinical results, combined with the high migration rate,
      mean that we no longer use this kind of implant. 

PMID- 24459252
TI  - Draft Genome Sequence of Clostridium botulinum Type B Strain Osaka05, Isolated
      from an Infant Patient with Botulism in Japan.
AB  - Clostridium botulinum strain Osaka05, which has been isolated from an infant
      patient with botulism in Japan, is the first strain producing botulinum
      neurotoxin subtype B6. Here, we report the draft genome sequence of C. botulinum
      Osaka05. 

PMID- 24459253
TI  - Complete Genome Sequence of Acinetobacter baumannii ZW85-1.
AB  - Acinetobacter baumannii is an aerobic, nonmotile Gram-negative bacterium that
      causes nosocomial infections worldwide. Here, we report the complete genome
      sequence of Acinetobacter baumannii strain ZW85-1 and its two plasmids. One of
      the plasmids carries genes for NDM-1, which can hydrolyze a wide range of
      antibiotics. 

PMID- 24459254
TI  - Complete Genome Sequence of the Sugar Cane Endophyte Pseudomonas aurantiaca PB
      St2, a Disease-Suppressive Bacterium with Antifungal Activity toward the Plant
      Pathogen Colletotrichum falcatum.
AB  - The endophytic bacterium Pseudomonas aurantiaca PB-St2 exhibits antifungal
      activity and represents a biocontrol agent to suppress red rot disease of sugar
      cane. Here, we report the completely sequenced 6.6-Mb genome of P. aurantiaca PB
      St2. The sequence contains a repertoire of biosynthetic genes for secondary
      metabolites that putatively contribute to its antagonistic activity and its plant
      microbe interactions. 

PMID- 24459255
TI  - Genome Sequences of Three Novel Bacillus cereus Bacteriophages.
AB  - The Bacillus cereus group is an assemblage of highly related firmicute bacteria
      that cause a variety of diseases in animals, including insects and humans. We
      announce three high-quality, complete genome sequences of bacteriophages we
      isolated from soil samples taken at the bases of fruit trees in Utah County,
      Utah. While two of the phages (Shanette and JL) are highly related myoviruses,
      the bacteriophage Basilisk is a siphovirus. 

PMID- 24459256
TI  - Genome Sequence of Bacillus sp. Strain FJAT-14515.
AB  - We report the draft genome sequence of Bacillus sp. strain FJAT-14515. The genome
      is 5.44 Mb in length. It covers 5,263 genes with an average length of 791 bp, has
      a G+C value of 37.06%, and contains 67 tRNAs, 31 small RNAs, and 5 rRNA loci. 

PMID- 24459257
TI  - Complete Genome Sequence of Pseudomonas aeruginosa MTB-1, Isolated from a
      Microbial Community Enriched by the Technical Formulation of
      Hexachlorocyclohexane.
AB  - Pseudomonas aeruginosa MTB-1 does not degrade gamma-hexachlorocyclohexane (gamma
      HCH), but this bacterium persistently coexists with a gamma-HCH-degrading strain,
      Sphingomonas sp. MM-1, in a microbial community enriched by the technical
      formulation of HCH. Here we report the complete MTB-1 genome sequence, with a 6.6
      Mb circular chromosome. 

PMID- 24459258
TI  - Draft Genome Sequence of the Alkaliphilic and Xylanolytic Paenibacillus sp.
      Strain JCM 10914, Isolated from the Gut of a Soil-Feeding Termite.
AB  - Panibacillus sp. strain JCM 10914 is a xylanolytic alkaliphile isolated from the
      gut of a soil-feeding termite. Its draft genome sequence revealed various genes
      for hydrolytic enzymes and will facilitate studies on adaptation to the highly
      alkaline gut environment and its role in digesting soil organic matter in the
      gut. 

PMID- 24459259
TI  - Draft Genome Sequence of Saccharomyces cerevisiae NAM34-4C, a Lactic Acid
      Assimilating Industrial Yeast Strain.
AB  - We determined the genome sequence of industrial Saccharomyces cerevisiae strain
      NAM34-4C, which would be useful for bioethanol production. The approximately 11.5
      Mb draft genome sequence of NAM34-4C will provide remarkable insights into
      metabolic engineering for effective production of bioethanol from biomass. 

PMID- 24459260
TI  - Revised Genome Sequence of Staphylococcus aureus Bacteriophage K.
AB  - Bacteriophage K is a member of the virulent Twort-like group of myophages
      infecting Staphylococcus aureus. The revised sequence presented here includes
      12,436 bp of additional sequence not present in the previously available phage K
      genome (GenBank accession no. NC_005880) and updated annotations, and has been
      reopened at the predicted terminal repeat boundary. 

PMID- 24459261
TI  - Genome Sequence of the Small-Colony Variant Pseudomonas aeruginosa MH27, Isolated
      from a Chronic Urethral Catheter Infection.
AB  - Pseudomonas aeruginosa is a notable nosocomial pathogen causing severe chronic
      infections. Here we present the draft genome sequence of P. aeruginosa MH27,
      isolated from a patient with a chronic hospital-acquired catheter-associated
      urinary tract infection. The 7.1-Mb genome sequence organized in 24 scaffolds
      contributes to the understanding of biofilm formation and antibiotic resistance. 

PMID- 24459262
TI  - Draft Genome Sequence of Sclerotinia borealis, a Psychrophilic Plant Pathogenic
      Fungus.
AB  - Sclerotinia borealis is a necrotrophic phytopathogenic fungus notable for its
      wide host range and environmental persistence. It grows at low temperatures,
      causing snow mold disease of crop plants. To understand the molecular mechanisms
      of its pathogenesis and adaptation to the psychrophilic lifestyle, we determined
      the 39.3-Mb draft genome sequence of S. borealis F-4128. 

PMID- 24459263
TI  - Draft Genome Sequence of Mortierella alpina Isolate CDC-B6842.
AB  - We report the draft genome sequence of Mortierella alpina isolate CDC-B6842. M.
      alpina is a nonpathogenic member of the Mucoromycotina subphylum of fungi that is
      an important model for understanding the molecular mechanisms of lipid production
      and metabolism. 

PMID- 24459264
TI  - Draft Genome Sequence of a Human-Associated Isolate of Methanobrevibacter
      arboriphilicus, the Lowest-G+C-Content Archaeon.
AB  - We report the draft genome sequence of Methanobrevibacter arboriphilicus strain
      ANOR1, isolated from the human gut. Its 2.21-Mb genome exhibits a 25.46% G+C
      content, the lowest value among archaea. The genome of M. arboriphilicus contains
      a total of 2,111 open reading frames and three clusters of regularly interspaced
      short palindromic repeat (CRISPR) loci with associated Cas proteins. 

PMID- 24459265
TI  - Genome Sequence of Youngiibacter fragilis, the Type Strain of the Genus
      Youngiibacter.
AB  - The genome of Youngiibacter fragilis, the type strain of the newly described
      genus Youngiibacter, was sequenced. The genome consists of 3.996 Mb, with a G+C
      content of 46.6 mol%. Y. fragilis originates from coal-bed methane-produced water
      and may provide insight into the microbiological basis of biogas production in
      coal beds. 

PMID- 24459266
TI  - Whole-Genome Sequencing of Salmonella enterica subsp. enterica Serovar Cubana
      Strains Isolated from Agricultural Sources.
AB  - We report the draft genomes of Salmonella enterica subsp. enterica serovar Cubana
      strain CVM42234, isolated from chick feed in 2012, and S. Cubana strain 76814,
      isolated from swine in 2004. The genome sizes are 4,975,046 and 4,936,251 bp,
      respectively. 

PMID- 24459267
TI  - Draft Genome Sequences of a Phylogenetically Diverse Suite of Pseudomonas
      syringae Strains from Multiple Source Populations.
AB  - Here, we report the draft genome sequences for 7 phylogenetically diverse
      isolates of Pseudomonas syringae, obtained from numerous environmental sources
      and geographically proximate crop species. Overall, these sequences provide a
      wealth of information about the differences (or lack thereof) between isolates
      from disease outbreaks and those from other sources. 

PMID- 24459268
TI  - Draft Genome Sequence of the Microbispora sp. Strain ATCC-PTA-5024, Producing the
      Lantibiotic NAI-107.
AB  - We report the draft genome sequence of Microbispora sp. strain ATCC-PTA-5024, a
      soil isolate that produces NAI-107, a new lantibiotic with the potential to treat
      life-threatening infections caused by multidrug-resistant Gram-positive
      pathogens. The draft genome of strain Microbispora sp. ATCC-PTA-5024 consists of
      8,543,819 bp, with a 71.2% G+C content and 7,860 protein-coding genes. 

PMID- 24459269
TI  - Complete Genome Sequence of Chlamydia trachomatis Ocular Serovar C Strain TW-3.
AB  - Chlamydia trachomatis is the etiological agent of trachoma, the leading
      infectious cause of blindness worldwide. We report here the first complete and
      annotated genome of a C. trachomatis trachoma-causing serovar C strain (strain TW
      3). The chromosome and plasmid are 1,043,554 bp and 7,501 bp in length,
      respectively. 

PMID- 24459270
TI  - Metagenomic sequencing of two salton sea microbiomes.
AB  - The Salton Sea is the largest inland body of water in California, with salinities
      ranging from brackish freshwater to hypersaline. The lake experiences high
      nutrient input, and its surface water is exposed to temperatures up to 40 degrees
      C. Here, we report the community profiles associated with surface water from the
      Salton Sea. 

PMID- 24459271
TI  - Draft Genome Sequence of Enterococcus faecalis Strain PF3, Isolated from Adelie
      Penguin Feces from Antarctica.
AB  - Enterococcus faecalis is one of the leading causes of nosocomial infections and
      is a common commensal organism in humans and other animals. In this study, we
      report a draft genome sequence for the E. faecalis strain PF3, isolated from
      Adelie penguin feces collected from Warriner Island, Antarctica. 

PMID- 24459272
TI  - Draft Genome Sequence of Marinomonas sp. Strain D104, a Polycyclic Aromatic
      Hydrocarbon-Degrading Bacterium from the Deep-Sea Sediment of the Arctic Ocean.
AB  - Marinomonas sp. strain D104 was isolated from a polycyclic aromatic hydrocarbon
      degrading consortium enriched from deep-sea sediment from the Arctic Ocean. The
      draft genome sequence of D104 (approximately 3.83 Mbp) contains 62 contigs and
      3,576 protein-encoding genes, with a G+C content of 44.8%. 

PMID- 24459273
TI  - Metagenome sequencing of the prokaryotic microbiota of the hypersaline and
      meromictic soap lake, washington.
AB  - Soap Lake is a small saline lake in central eastern Washington that is sharply
      stratified into two layers. In addition to being highly alkaline (~pH 10), Soap
      Lake also contains high concentrations of sulfide. Here, we report the community
      profile of the prokaryotic microbiota associated with Soap Lake surface water. 

PMID- 24459274
TI  - Complete Genome Sequence of the Thermophilic Polychlorinated Biphenyl Degrader
      Geobacillus sp. Strain JF8 (NBRC 109937).
AB  - Geobacillus sp. strain JF8 (NBRC 109937) utilizes biphenyl and naphthalene as
      sole carbon sources and degrades polychlorinated biphenyl (PCB) at 60 degrees C.
      Here, we report the complete nucleotide sequence of the JF8 genome (a 3,446,630
      bp chromosome and a 39,678-bp plasmid). JF8 has the smallest genome among the
      known PCB degraders. 

PMID- 24459275
TI  - Genome Sequence of a Helicobacter pylori Strain Isolated from a Mexican Patient
      with Intestinal Gastric Cancer.
AB  - Helicobacter pylori strains are the major risk factor for gastric cancer. Strains
      vary in their content of disease-associated genes, so genome-wide analysis of
      cancer-isolated strains will help elucidate their pathogenesis and genetic
      diversity. We present the draft genome sequence of H. pylori isolated from a
      Mexican patient with intestinal gastric cancer. 

PMID- 24459276
TI  - Draft Genome Sequence of Brevibacillus panacihumi Strain W25, a Halotolerant
      Hydrocarbon-Degrading Bacterium.
AB  - Brevibacillus panacihumi strain W25 was isolated from hydrocarbon-contaminated
      saline soil. Here, we report the 5.5-Mb draft genome sequence of this strain,
      which may provide insights into the mechanism of microbial hydrocarbon
      degradation in saline environments. 

PMID- 24459277
TI  - Complete Genome Sequence of Paenibacillus polymyxa CR1, a Plant Growth-Promoting
      Bacterium Isolated from the Corn Rhizosphere Exhibiting Potential for Biocontrol,
      Biomass Degradation, and Biofuel Production.
AB  - Here we report the complete genome sequence of the bacterium Paenibacillus
      polymyxa CR1 (accession no. CP006941), which consists of one circular chromosome
      of 6,024,666 bp with 5,283 coding sequences (CDS), 87 tRNAs, and 12 rRNA operons.
      Data presented will allow for further insights into the mechanisms underpinning
      agriculturally and industrially relevant processes. 

PMID- 24459278
TI  - Complete Genome Sequence of Salmonella enterica Serovar Agona Pulsed-Field Type
      SAGOXB.0066, Cause of a 2008 Pan-European Outbreak.
AB  - Salmonella enterica serovar Agona is in the top 10 most common nontyphoidal
      serovars reported in humans in the European Union. Here we report the complete
      genome sequence of an S. enterica serovar Agona isolate, designated 24249, that
      was the cause of a pan-European outbreak in 2008 with 163 confirmed cases
      reported. 

PMID- 24459279
TI  - Complete Genome Sequence of Mycobacterium tuberculosis Strain MtURU-001, Isolated
      from a Rapidly Progressing Outbreak in Uruguay.
AB  - Despite efficient control programs, large clonal outbreaks of tuberculosis (TB)
      may arise in low-risk populations. Recently, an unusual TB outbreak was reported
      in Uruguay, reaching an elevated disease attack rate (53 to 69%). Here, we report
      the genome sequence of the Mycobacterium tuberculosis strain associated with this
      rapidly progressing outbreak, named MtURU-001. 

PMID- 24459280
TI  - Genome Sequence of Pyrethroid-Degrading Bacterium Rhodopseudomonas palustris
      Strain JSC-3b.
AB  - Rhodopseudomonas palustris strain JSC-3b is a facultative, thermophilic
      bacterium, which was isolated from water in a canal adjacent to a vegetable
      field. Strain JSC-3b biodegrades several varieties of pyrethroid residues
      effectively through cometabolic pathways. Here, we present the genome sequence of
      this biodegrader. 

PMID- 24459281
TI  - Whole-Genome Sequencing of Erwinia amylovora Strains from Mexico Detects Single
      Nucleotide Polymorphisms in rpsL Conferring Streptomycin Resistance and in the
      avrRpt2 Effector Altering Host Interactions.
AB  - We report draft genome sequences of three Mexican Erwinia amylovora strains. A
      novel plasmid, pEA78, was identified. Comparative genomics revealed an rpsL
      chromosomal mutation conferring high-level streptomycin resistance in two
      strains. In the effector gene avrRpt2, a single nucleotide polymorphism was
      detected that overcomes fire blight disease resistance in Malus * robusta 5. 

PMID- 24459282
TI  - Draft Genome Sequence of Williamsia sp. Strain D3, Isolated From the Darwin
      Mountains, Antarctica.
AB  - Actinobacteria are the dominant taxa in Antarctic desert soils. Here, we describe
      the first draft genome of a member of the genus Williamsia (strain D3) isolated
      from Antarctic soil. The genome of this psychrotolerant bacterium may help to
      elucidate crucial survival mechanisms for organisms inhabiting cold desert soil
      systems. 

PMID- 24459283
TI  - Complete Genome Sequence of Highly Adherent Pseudomonas aeruginosa Small-Colony
      Variant SCV20265.
AB  - The evolution of small-colony variants within Pseudomonas aeruginosa populations
      chronically infecting the cystic fibrosis lung is one example of the emergence of
      adapted subpopulations. Here, we present the complete genome sequence of the
      autoaggregative and hyperpiliated P. aeruginosa small-colony variant SCV20265,
      which was isolated from a cystic fibrosis (CF) patient. 

PMID- 24459284
TI  - Draft Genome Sequences of Fusobacterium nucleatum ChDC F145, ChDC F174, ChDC
      F206, and ChDC F300, Isolated from Human Subgingival Plaques in the Republic of
      Korea.
AB  - Recently, five strains were isolated from human subgingival plaques and were
      proposed as a novel subspecies of Fusobacterium nucleatum. Here, we report the
      draft genome sequences of the strains, except one for which the draft sequence
      was already introduced. 

PMID- 24459285
TI  - BuT2 is a member of the third major group of hAT transposons and is involved in
      horizontal transfer events in the genus Drosophila.
AB  - The hAT superfamily comprises a large and diverse array of DNA transposons found
      in all supergroups of eukaryotes. Here we characterized the Drosophila buzzatii
      BuT2 element and found that it harbors a five-exon gene encoding a 643-aa
      putatively functional transposase. A phylogeny built with 85 hAT transposases
      yielded, in addition to the two major groups already described, Ac and Buster, a
      third one comprising 20 sequences that includes BuT2, Tip100, hAT-4_BM, and RP
      hAT1. This third group is here named Tip. In addition, we studied the
      phylogenetic distribution and evolution of BuT2 by in silico searches and
      molecular approaches. Our data revealed BuT2 was, most often, vertically
      transmitted during the evolution of genus Drosophila being lost independently in
      several species. Nevertheless, we propose the occurrence of three horizontal
      transfer events to explain its distribution and conservation among species.
      Another aspect of BuT2 evolution and life cycle is the presence of short related
      sequences, which contain similar 5' and 3' regions, including the terminal
      inverted repeats. These sequences that can be considered as miniature inverted
      repeat transposable elements probably originated by internal deletion of complete
      copies and show evidences of recent mobilization. 

PMID- 24459286
TI  - Domestication and the mitochondrial genome: comparing patterns and rates of
      molecular evolution in domesticated mammals and birds and their wild relatives.
AB  - Studies of domesticated animals have led to the suggestion that domestication
      could have significant effects on patterns of molecular evolution. In particular,
      analyses of mitochondrial genome sequences from domestic dogs and yaks have
      yielded higher ratios of non-synonymous to synonymous substitutions in the
      domesticated lineages than in their wild relatives. These results are important
      because they imply that changes to selection or population size operating over a
      short timescale can cause significant changes to the patterns of mitochondrial
      molecular evolution. In this study, our aim is to test whether the impact on
      mitochondrial genome evolution is a general feature of domestication or whether
      it is specific to particular examples. We test whether domesticated mammals and
      birds have consistently different patterns of molecular evolution than their wild
      relatives for 16 phylogenetically independent comparisons of mitochondrial genome
      sequences. We find no consistent difference in branch lengths or dN/dS between
      domesticated and wild lineages. We also find no evidence that our failure to
      detect a consistent pattern is due to the short timescales involved or low
      genetic distance between domesticated lineages and their wild relatives. However,
      removing comparisons where the wild relative may also have undergone a bottleneck
      does reveal a pattern consistent with reduced effective population size in
      domesticated lineages. Our results suggest that, although some domesticated
      lineages may have undergone changes to selective regime or effective population
      size that could have affected mitochondrial evolution, it is not possible to
      generalize these patterns over all domesticated mammals and birds. 

PMID- 24459289
TI  - omega-3 fatty acids, atherosclerosis progression and cardiovascular outcomes in
      recent trials: new pieces in a complex puzzle.

PMID- 24459290
TI  - Associations with anticoagulation: a cross-sectional registry-based analysis of
      stroke survivors with atrial fibrillation.
AB  - OBJECTIVE: To describe vitamin K antagonist (VKA) anticoagulation prescribing
      patterns in stroke survivors with atrial fibrillation (AF), with particular
      emphasis on sociodemographic associations with VKA prescription. METHODS: We
      conducted a cross-sectional analysis of city-wide Glasgow primary care data held
      as part of the Local Enhanced Services (LES) for the year 2010. We collated
      clinical and sociodemographic data of community-dwelling ischaemic stroke
      survivors with AF, including risk factors; comorbidity; socioeconomic status and
      prescribing. We described stroke risk and bleeding risk using recommended
      stratification tools (CHA2DS2-VASC and HAS-BLED). Univariate and multivariate
      associations with anticoagulant prescription were described by ORs and
      corresponding 95% CI. RESULTS: We identified 3429 community-dwelling, ischaemic
      stroke survivors with AF; median age 78 (IQR 72-84); 1699 (49%) male. Median
      CHA2DS2-VASC score was 5 (IQR 4-6). VKA was prescribed in 1165 (34%). On
      univariate analysis, higher CHA2DS2-VASC was associated with fewer VKA
      prescriptions (OR 0.90, 95% CI 0.45 to 0.95). On multivariate analysis, older age
      (OR 0.97, 95% CI 0.96 to 0.98) and higher deprivation scores (OR 0.59, 95% CI
      0.57 to 0.76) were independently associated with non-prescription of VKA.
      CONCLUSIONS: Anticoagulation was underused in this high-risk population, and
      those at highest risk were less likely to be treated. Strategies need to be
      developed to improve prescription of anticoagulation treatment.

PMID- 24459291
TI  - Transcutaneous aortic valve replacement with the Edwards SAPIEN XT and Medtronic
      CoreValve prosthesis under fluoroscopic guidance and local anaesthesia only.
AB  - OBJECTIVE: To assess the feasibility of transcatheter aortic valve implantation
      (TAVI; Medtronic CoreValve and Edwards SAPIEN XT) under local anaesthesia with
      only mild analgesic medication and fluoroscopic guidance. METHODS: 461 patients
      underwent TAVI under local anaesthesia with lidocaine. The procedure was
      performed successfully in 459 of the cases. All patients were also treated with
      piritramide, metoclopramide hydrochloride and 62 mg dimenhydrinate. Monitoring
      consisted of a six-electrode, virtual 12-lead ECG, pulse oximetry, and invasive
      arterial pressure measurement. There was no continuous surveillance by an
      anaesthesiologist. RESULTS: There was no need for conversion to general
      anaesthesia except in four patients who required cardiopulmonary resuscitation.
      Conscious sedation with intravenous administration of midazolam for agitation or
      inotropic medication for prolonged hypotension was necessary in only seven of the
      461 patients. The combined safety end point according to the Valve Academic
      Research Consortium consensus document was reached in 12.6%. CONCLUSIONS: Our
      results show that TAVI performed under local anaesthesia with only mild analgesic
      medication and under fluoroscopic guidance is feasible, with good outcome
      comparable to published data.

PMID- 24459292
TI  - The Bradford-Hill criteria and evidence of association between influenza
      vaccination and ischaemic heart disease.

PMID- 24459293
TI  - Imaging of myocardial fibrosis in hypertrophic cardiomyopathy: what is the gold
      standard?

PMID- 24459294
TI  - Rare and private variations in neural crest, apoptosis and sarcomere genes define
      the polygenic background of isolated Tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease.
      Its genetic basis is demonstrated by an increased recurrence risk in siblings and
      familial cases. However, the majority of TOF are sporadic, isolated cases of
      undefined origin and it had been postulated that rare and private autosomal
      variations in concert define its genetic basis. To elucidate this hypothesis, we
      performed a multilevel study using targeted re-sequencing and whole-transcriptome
      profiling. We developed a novel concept based on a gene's mutation frequency to
      unravel the polygenic origin of TOF. We show that isolated TOF is caused by a
      combination of deleterious private and rare mutations in genes essential for
      apoptosis and cell growth, the assembly of the sarcomere as well as for the
      neural crest and secondary heart field, the cellular basis of the right ventricle
      and its outflow tract. Affected genes coincide in an interaction network with
      significant disturbances in expression shared by cases with a mutually affected
      TOF gene. The majority of genes show continuous expression during adulthood,
      which opens a new route to understand the diversity in the long-term clinical
      outcome of TOF cases. Our findings demonstrate that TOF has a polygenic origin
      and that understanding the genetic basis can lead to novel diagnostic and
      therapeutic routes. Moreover, the novel concept of the gene mutation frequency is
      a versatile measure and can be applied to other open genetic disorders.

PMID- 24459297
TI  - Prof. J. K. Trivedi.

PMID- 24459295
TI  - Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic
      neuronal degeneration in Drosophila.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are common causes of familial
      Parkinson's disease (PD). LRRK2 has been shown to bind peroxiredoxin-3 (PRDX3),
      the most important scavenger of hydrogen peroxide in the mitochondria, in vitro.
      Here, we examined the interactions of LRRK2 and PRDX3 in Drosophila models by
      crossing transgenic LRRK2 and PRDX3 flies. As proof of principle experiments, we
      subsequently challenged LRRK2 and LRRK2/PRDX3 flies with a peroxidase mimic,
      Ebselen. We demonstrated that co-expression of PRDX3 with the LRRK2 kinase mutant
      G2019S in bigenic Drosophila ameliorated the G2019S mutant-induced reduction in
      peroxidase capacity, loss of dopaminergic neurons, shortened lifespan and
      mitochondrial defects of flight muscles in monogenic flies expressing the G2019S
      alone. Challenges with Ebselen recapitulated similar rescue of these phenotypic
      features in mutant-expressing Drosophila. The peroxidase mimic preserved neuronal
      and mitochondrial and neuronal integrity and improved mobility and survival in
      mutant-expressing Drosophila. Taken together, our study provides the first in
      vivo evidence to suggest that phosphoinhibition of endogenous peroxidases could
      be a mechanism in LRRK2-induced oxidant-mediated neurotoxicity. Our therapeutic
      experiments also highlight the potential of thiol peroxidases as neuroprotective
      agents in PD patients carrying LRRK2 mutations.

PMID- 24459298
TI  - Psychosomatic paradigms in psoriasis: Psoriasis, stress and mental health.

PMID- 24459296
TI  - Identification of a post-translationally myristoylated autophagy-inducing domain
      released by caspase cleavage of huntingtin.
AB  - Huntington disease (HD) is a debilitating neurodegenerative disease characterized
      by the loss of motor control and cognitive ability that ultimately leads to
      death. It is caused by the expansion of a polyglutamine tract in the huntingtin
      (HTT) protein, which leads to aggregation of the protein and eventually cellular
      death. Both the wild-type and mutant form of the protein are highly regulated by
      post-translational modifications including proteolysis, palmitoylation and
      phosphorylation. We now demonstrate the existence of a new post-translational
      modification of HTT: the addition of the 14 carbon fatty acid myristate to a
      glycine residue exposed on a caspase-3-cleaved fragment (post-translational
      myristoylation) and that myristoylation of this fragment is altered in a
      physiologically relevant model of mutant HTT. Myristoylated HTT553-585-EGFP, but
      not its non-myristoylated variant, initially localized to the ER, induced the
      formation of autophagosomes and accumulated in abnormally large
      autophagolysosomal/lysosomal structures in a variety of cell types, including
      neuronal cell lines under nutrient-rich conditions. Our results suggest that
      accumulation of myristoylated HTT553-586 in cells may alter the rate of
      production of autophagosomes and/or their clearance through the heterotypic
      autophagosomal/lysosomal fusion process. Overall, our novel observations
      establish a role for the post-translational myristoylation of a caspase-3-cleaved
      fragment of HTT, highly similar to the Barkor/ATG14L autophagosome-targeting
      sequence domain thought to sense, maintain and/or promote membrane curvature in
      the regulation of autophagy. Abnormal processing or production of this
      myristoylated HTT fragment might be involved in the pathophysiology of HD.

PMID- 24459299
TI  - Sexual abuse in women with special reference to children: Barriers, boundaries
      and beyond.

PMID- 24459300
TI  - Loneliness: A disease?

PMID- 24459301
TI  - Group psychotherapies for depression in persons with HIV: A systematic review.
AB  - Studies investigating effectiveness of group psychotherapy intervention in
      depression in persons with HIV have showed varying results with differing effect
      sizes. A systematic review of randomized controlled trials of group psychotherapy
      in depression in persons with HIV has been conducted to present the best
      available evidence in relation to its effect on depressive symptomatology.
      Electronic databases were searched to identify randomized controlled trials.
      Selected studies were quality assessed and data extracted by two reviewers. If
      feasible, it was planned to conduct a meta-analysis to obtain a pooled effect
      size of group psychotherapeutic interventions on depressive symptoms. Odds ratio
      for drop out from group was calculated. The studies were assessed for their
      quality using the Quality Rating Scale and other parameters for quality
      assessment set out by COCHRANE. The quality of reporting of the trials was
      compared against the Consolidated Standards of Reporting Trials (CONSORT)
      checklist for non-pharmacological studies (CONSORT-NPT). Four studies met the
      full inclusion criteria for systematic review. The trials included in the review
      examined group interventions based on the Cognitive behavioral therapy model
      against other therapeutic interventions or waiting list controls. In all four
      studies, group psychotherapy was an effective intervention for reducing
      depressive symptoms in persons with HIV in comparison to waiting list controls.
      The reported benefits from the group psychotherapy in comparison to active
      controls were less impressive. There were no statistically significant
      differences in drop outs at post treatments across group psychotherapy, wait list
      control, and other active interventions. The methodological quality of the
      studies varied. The quality of reporting of the studies was sub-optimal. The
      results of this systematic review support that group psychological interventions
      for depression in persons with HIV have a significant effect on depressive
      symptomatology. This review also indicates that group cognitive behavioral
      therapies are an acceptable psychological intervention for persons with HIV and
      comorbid depression. 

PMID- 24459302
TI  - Assessment of cognition in non-affected full biological siblings of patients with
      schizophrenia.
AB  - BACKGROUND: Schizophrenia is a devastating psychotic illness which is like the
      most mental disorders, shows complex inheritance; the transmission of the
      disorder most likely involves several genes and environmental factors. It is
      difficult to judge whether a particular person without schizophrenia has
      predisposing factors for the said disease. A few studies have shown the relative
      sensitivity and reliability of cognitive and psychophysiological markers of brain
      function as the susceptibility factors for schizophrenia which may aid us to find
      people with an increased risk of complex disorders like schizophrenia. The
      present work is an exploration on cognitive impairments in unaffected siblings of
      patients suffering from schizophrenia with a framework to explore why a mental
      disorder occurs in some families but not in others. MATERIALS AND METHODS: This
      is a single point non-invasive study of non-affected full biological siblings of
      patients with schizophrenia, involving administration of a battery of
      neuropsychological tests to assess the cognitive function in the sibling group
      and a control group of volunteers with no history of psychiatric illness. The
      control group was matched for age, gender, and education. The siblings were also
      divided on the basis of the type of schizophrenia their siblings (index probands)
      were suffering from and their results compared with each other. RESULTS: The
      siblings performed significantly poorly as compared to the controls on Wisconsin
      card sorting test (WCST), continuous performance test (CPT), and spatial working
      memory test (SWMT). The comparison between the sibling subgroups based on the
      type of schizophrenia in the index probands did not reveal any significant
      difference. CONCLUSION: These findings suggest that there is a global impairment
      in the cognition of the non-affected siblings of patients of schizophrenia.
      Cognitive impairment might be one of the factors which will help us to hit upon
      people who are predisposed to develop schizophrenia in the future.

PMID- 24459303
TI  - Prevalence of Attention Deficit Hyperactivity Disorder in primary school
      children.
AB  - CONTEXT: There is a lacuna of studies on Attention Deficit Hyperactivity Disorder
      (ADHD) in the Indian context. AIMS: (i) To identify the prevalence of ADHD in
      primary school children, (ii) To identify the gender difference in the prevalence
      of ADHD, (iii) To compare the distribution of ADHD among different socioeconomic
      status, (iv) To identify the presence of any co-morbid factors associated with
      ADHD. SETTINGS AND DESIGN: This is a cross sectional study of school aged
      children selected from four different schools in Coimbatore district. MATERIALS
      AND METHODS: Seven hundred seventy children aged between 6 and 11 years were
      selected from four schools in Coimbatore district after obtaining informed
      consent from their parents. The presence of ADHD was assessed by using Conner's
      Abbreviated Rating Scale (CARS) given to parents and teachers. The children
      identified as having ADHD were assessed for the presence of any co-morbid factors
      by administering Children's Behavioural Questionnaire (CBQ) to the teachers and
      Personal Information Questionnaire to the parents. STATISTICAL ANALYSIS:
      Statistical Product and Service Solutions (SPSS) 10 software, Mean and Standard
      Deviation, and student's t test were used for statistical analysis. RESULTS: The
      prevalence of ADHD among primary school children was found to be 11.32%.
      Prevalence was found to be higher among the males (66.7%) as compared to that of
      females (33.3%). The prevalence among lower socio-economic group was found to be
      16.33% and that among middle socio-economic group was 6.84%. The prevalence was
      highest in the age group 9 and 10 years. CONCLUSION: The present study shows a
      high prevalence of ADHD among primary school children with a higher prevalence
      among the males than the females.

PMID- 24459304
TI  - Post-stroke depression and lesion location: A hospital based cross-sectional
      study.
AB  - BACKGROUND: Depression is a common neuro-psychiatric consequence of stroke,
      affecting approximately 40% of the patients. Many studies show that in addition
      to the psychosocial stress, neurobiological factors such as site of infarct and
      brain atrophy may also be related to Post Stroke Depression (PSD). There are
      conflicting results in this area of research and paucity of such data in Indian
      literature. Thus the aim of this study is to weigh the importance of lesion
      location in PSD. MATERIALS AND METHODS: Sixty two subjects with their first ever
      stroke were interviewed using a semi-structured proforma and PSD diagnosed using
      MINI Plus interview. Scales of Beck Depression Inventory and Montgomery Asberg
      Depression Rating Scale were used to assess severity of depression. Mini mental
      state examination was used to assess cognitive impairment and Barthel Index to
      measure Activities of Daily Living. Neuro-imaging provided information on site
      and side of lesion. Collected data was analysed using SPSS version 15.0. RESULTS:
      PSD was diagnosed in 28 subjects, amongst who 19 had left sided lesions. Left
      sided cortical infarcts and sub cortical infarcts showed statistically
      significant association with PSD. CONCLUSION: Results are in keeping with
      previous landmark studies. Differences in emotional reactions depending on
      hemisphere and site of the infarct as shown in this study suggest organic
      biological basis for post stroke depression. Understanding the etiological basis
      would allow clinicians to monitor patients at risk of developing PSD, enabling
      early detection and treatment thus improving their quality of life and
      rehabilitation.

PMID- 24459305
TI  - Efficacy of yoga for mental performance in university students.
AB  - BACKGROUND: With growing scientific evidence, yoga is emerging as an important
      health behavior-lifestyle modifying module to achieve holistic health at
      physical, mental, emotional, social and spiritual levels. Brain wave coherence
      (BWC) recordings from the surface of the skull are associated with different
      cognitive processes and plays both critical and useful roles in yoga with wide
      range of functional significance. The psycho-physiological changes that
      characterize the efficacy of yoga for better mental performance in university
      students have not been studied adequately. OBJECTIVE: The study was designed to
      assess the mental performance through BWC analysis in university students
      undergoing Integrated Yoga Module (IYM). MATERIALS AND METHODS: The IYM subjects
      (n=30) with 25.77+/-4.85 years of mean age participated in this single group pre
      post study. The BWC data was collected before (pre) and after (post) the 21 days
      IYM using Brain Master (Model: 2E Part # 390-001), Michigan, USA. STATISTICAL
      ANALYSIS: Means, standard deviations, Kolmogorov-Smirnov test and Wilcoxon signed
      rank test were used for analyzing data with the help of SPSS-16. RESULTS: A
      complete statistical and spectral analysis showed 43.24% increase (P<0.001) in
      Delta, 9.13% increase (P=0.289) in Theta, 57.85% increase (P<0.001) in Alpha,
      17.65% decrease (P=0.136) in Beta and 9.19% increase (P=0.586) in Gamma BWC
      between pre and post intervention measurements. CONCLUSION: BWC study showed
      significant increase in both Delta and Alpha wave coherence suggesting that IYM
      can result in improvement of coherent and integrated brain functioning among
      students, thus paving the way for their better mental performance. Although this
      preliminary research is promising, more well-designed studies are needed before a
      strong recommendation can be made.

PMID- 24459306
TI  - Prevalence and pattern of psychiatric morbidity and health related quality of
      life in patients with ischemic heart disease in a tertiary care hospital.
AB  - BACKGROUND: Psychiatric morbidity and Health Related Quality of Life (Hr-QoL) in
      Ischemic Heart Disease (IHD) are relatively less studied in our country. AIMS:
      This cross-sectional observational study was undertaken to assess the common
      psychiatric disorders and Hr-QoL in IHD. MATERIALS AND METHODS: One-hundred and
      thirty patients with IHD were evaluated for psychiatric morbidity and Hr-QoL.
      Tools used were SCID-1, Euro QoL-5D, and Socio-demographic data sheet. The data
      were analyzed using SPSS v 10.0 software, Chi-square test, T-test, ANOVA were
      used as needed. RESULTS: Psychiatric morbidity was assessed using psychiatric
      assessment schedule SCID-I for generating diagnosis as per DSM-IV criteria. Major
      depressive disorder was found in 34.6% (n=45) patients. 23.8% (n=31) patients had
      a diagnosis of depression due to general medical condition. Anxiety disorder due
      to general medical condition was present in 36.9% (n=48) patients. Around 95.4%
      of patients reported psychiatric symptoms, either depression or anxiety. Though
      widely disputed, low educational status was reported as significantly associated
      with psychiatric morbidity in IHD. Female sex of the patient and the presence of
      diabetes mellitus were associated with psychiatric morbidity in a significant
      manner. Majority of patients with poor quality of life were in the domain of
      anxiety/depression. CONCLUSION: The findings of our study reveal a high rate of
      psychiatric morbidity and impaired quality of life in IHD Patients.

PMID- 24459307
TI  - Psychiatric morbidity and marital satisfaction among spouses of men with alcohol
      dependence.
AB  - BACKGROUND: Alcohol dependence has adverse health and social consequences;
      Alcohol related problems primarily occur within the family context and maximum
      impact is felt on spouses, given the intimate nature of their relationship.
      Spouses play an important role in treatment programs related to alcohol. There is
      thus a need to study psychiatric morbidity and marital satisfaction in spouses of
      alcohol dependent patients in order to understand and address such issues. AIMS:
      The aim of this study was to assess the pattern of psychiatric morbidity, marital
      satisfaction in spouses of men with alcohol dependence syndrome and explore the
      association. MATERIALS AND METHODS: For psychiatric morbidity, 60 spouses of men
      with alcohol dependence syndrome were evaluated. Marital satisfaction was
      assessed using the marital satisfaction scale. Severity of alcohol dependence in
      the husbands and consequences of drinking was assessed using short alcohol
      dependence data and drinkers inventory of consequences respectively. RESULTS:
      More than half of the spouses (65%) had a psychiatric disorder. Primarily mood
      and anxiety disorder were present. Major depressive disorder was present in 43%.
      Psychiatric morbidity, marital dissatisfaction in spouses and higher adverse
      consequences alcohol dependence in their husbands, were found to be significantly
      correlated with each other and their association was robust particularly when
      problems in the physical, interpersonal and intrapersonal domains were high.
      CONCLUSION: Psychological distress and psychiatric morbidity in spouses of
      alcohol dependent men is high, with marital satisfaction being low. Addressing
      these issues will be beneficial as spouses are known to play an important role in
      the treatment of alcohol dependence syndrome.

PMID- 24459308
TI  - Psychiatric morbidity in prisoners.
AB  - BACKGROUND: Prisoners are having high percentage of psychiatric disorders.
      Majority of studies done so far on prisoners are from Western countries and very
      limited studies from India. AIM: Study socio-demographic profile of prisoners of
      a central jail and to find out current prevalence of psychiatric disorders in
      them. MATERIALS AND METHODS: 118 prisoners were selected by random sampling and
      interviewed to obtain socio-demographic data and assessed on Indian Psychiatric
      Interview Schedule (IPIS) with additional required questions to diagnose
      psychiatric disorders in prisoners. RESULTS: Mean age of prisoners was 33.7 years
      with 97.5% males, 57.6% from rural areas and 65.3% were married. Average
      education in studied years was 6.6 years and 50.8% were unskilled workers. 47.4%
      were murderers while 20.3% of drugs related crimes. 47.5% were convicted and
      history of criminal behavior in family was in 32.2% prisoners. Current prevalence
      of psychiatric disorders was 33%. Psychotic, depressive, and anxiety disorders
      were seen in 6.7%, 16.1%, and 8.5% prisoners respectively. 58.8% had history of
      drug abuse/dependence prior to imprisonment. CONCLUSION: One prison of Hadoti
      region of Rajasthan is full of people with mental-health problems who
      collectively generate significant levels of unmet psychiatric treatment need.
      Prisons are detrimental to mental-health. Beginning of reforms is the immediate
      need.

PMID- 24459309
TI  - Chromosome 18p11.2 harbors susceptibility marker: D18S452, for bipolar affective
      disorder.
AB  - AIM: The aim of our study was to investigate whether the tandem repeat
      polymorphism in D18S452 microsatellite marker at locus 18p11.2 is a risk factor
      of bipolar affective disorder (BPAD) in Kashmiri population. MATERIALS AND
      METHODS: The repeat polymorphism in D18S452 was evaluated by polymerase chain
      reaction (PCR) analysis of in 74 diagnosed BPAD patients and 74 controls
      subjects. RESULTS: Tandem repeat (300 bp*) allele frequency was found to be 1.35%
      in controls and 8.108% in cases. The tandem repeat (250 bp*) allele frequency was
      found to be in 91.89% in cases and 98.65% in controls. The 252 bp/252 bp genotype
      was found to be present in 89.18% of cases and 98.64% of controls, the 300 bp/300
      bp genotype in 5.40% of cases and 1.35% of controls and the 252 bp/300 bp variant
      in 5.40% of cases and none among the controls. Although the proportion of
      patients homozygous for tandem repeat (300 bp/300 bp) was higher in cases than in
      controls, the difference was not statistically significant when 252 bp/252 bp
      genotype was taken as reference (odds ratio [OR]=4.4242; 95% confidence interval
      [CI] 0.4822-40.5924); P=0.1529). However, when the frequency of heterozygous
      genotype (252 bp/300 bp) was compared with 252 bp/252 bp statistical significance
      was observed (OR=8.0603; 95% CI 1.1112-58.4646; P=0.0383). CONCLUSION: This is
      the first study reporting a significant association between D18S452 maker with
      tandem repeat polymorphism in heterozygous condition (252 bp/300 bp) and the
      development of BPAD in Kashmiri population.

PMID- 24459311
TI  - Body dysmorphic disorder: Borderline category between neurosis and psychosis.
AB  - Body dysmorphic disorder is an under-recognised chronic problem, which is
      established as independent diagnostic entity. Its clinical features, co
      morbidity, course, and prognosis have been studied in detail. But the issue of
      its psychotic and non-psychotic variants and the question of dimensional or
      categorical method of classifying this disorder still poses a diagnostic dilemma.
      This case report tries to highlight on this issue. 

PMID- 24459310
TI  - The course and outcome of alcohol use disorders in men in Goa: A population-
      based follow-up study.
AB  - BACKGROUND: Research on the natural history and long-term outcomes of alcohol use
      disorders (AUD) is important to guide health policy. However, attrition is a
      major challenge in longitudinal studies and can affect validity of findings.
      MATERIALS AND METHODS: A 4-year follow-up study was conducted on a randomly
      selected subgroup of a sample of men in rural and urban communities in Goa to
      assess attrition, preliminary estimates of AUD outcomes, and chronic disease risk
      factors. RESULTS: Overall attrition rate was 16.7% with a higher attrition in AUD
      compared to abstainers or casual drinkers. Incidence of AUD at 4 years was 12.8%
      while the persistence rate of AUD was 53.9%. A trend for poorer health and health
      behaviors and higher blood pressure was observed in AUD. CONCLUSION: The results
      of this study suggest a relatively low attrition rate despite the long follow-up
      period and support the feasibility of conducting a definitive cohort study with
      the entire sample.

PMID- 24459312
TI  - Dothiepin-induced transient hypomania and extrapyramidal syndrome.
AB  - A case has been reported here, who developed transient hypomanic symptoms as well
      as extrapyramidal symptoms after being switched from sertraline to dothiepin
      therapy. The possible mechanisms and clinical implications of the same are
      discussed. 

PMID- 24459313
TI  - A case of Hallervorden-Spatz disease presenting as catatonic schizophrenia.
AB  - Hallervorden-Spatz disease belongs to a group of disorders characterized by
      predominant involvement of basal ganglia. These cases may present to the
      psychiatrist with symptoms of depression, nervousness and rarely other psychotic
      symptoms. Very few cases of this disease have been reported from India. We report
      a case of Hallervorden-Spatz disease that presented to the psychiatry outpatient
      department with catatonia. This case highlights how presentation of Hallervorden
      Spatz disease may overlap with catatonic symptoms and hence a high index of
      suspicion is required to make an accurate diagnosis. 

PMID- 24459314
TI  - Emetophobia: A fear of vomiting.
AB  - Emetophobia is an intense, irrational fear of vomiting including fear of feeling
      nausea, seeing or hearing another person vomit, or seeing vomitus itself. It may
      occur at any age and we need to understand its symptomatology. We report a case
      of emetophobic child whose fear of vomiting started after an attack of acute
      appendicitis. In the initial stage, fear was limited to vomiting, later it became
      generalized to a fear of seeing the vomitus, worries that parents may suffer
      vomiting, fear of vomiting in public places followed by avoiding social
      activities. Patient improved on short course of anti-anxiety drugs and Graded
      Exposure Therapy. 

PMID- 24459315
TI  - Forensic evaluations in psychiatry.
AB  - Forensic psychiatry is an important subspecialty of psychiatry. Forensic
      psychiatrists play an important role in the society in assisting the judiciary in
      many complicated cases. In India, forensic psychiatry work is undertaken mostly
      by the general psychiatrists. Forensic psychiatric assessments are often
      associated with an element of anxiety or fear for a young psychiatrist. The
      present paper aims at familiarizing the readers with forensic evaluation in
      various situations so that they are able to carry out the assessments in real
      life situations comfortably. Various steps of forensic assessment in different
      situations are discussed in the background of real-life cases. Assessment areas
      include criminal responsibility, fitness to plead, issue of guardianship,
      assessment of mental status, testamentary capacity and others. The paper gives
      some general guidelines on forensic psychiatric assessment in practical
      situations in our country. The readers are advised to refer to the standard
      textbooks and the Indian law for further details. 

PMID- 24459316
TI  - Music and mind.

PMID- 24459317
TI  - The rise of super (?sub)-specialties courses in psychiatry: Is India ready for it
      !

PMID- 24459318
TI  - Dissociative identity disorder: An uncommon psychiatric disorder reported.

PMID- 24459319
TI  - Studies on posttraumatic stress disorder: Challenges ahead.

PMID- 24459320
TI  - Prolonged, self-administration of ultra-high doses of quetiapine.

PMID- 24459321
TI  - Alcohol use among in-patients of a medical college hospital in Delhi.

PMID- 24459322
TI  - Job stress among emergency nursing staff: A preliminary study.

PMID- 24459323
TI  - Have you forgotten?

PMID- 24459324
TI  - Overview of the taxonomy of zooxanthellate Scleractinia.
AB  - Coral taxonomy has entered a historical phase where nomenclatorial uncertainty is
      rapidly increasing. The fundamental cause is mandatory adherence to historical
      monographs that lack essential information of all sorts, and also to type
      specimens, if they exist at all, that are commonly unrecognizable fragments or
      are uncharacteristic of the species they are believed to represent. Historical
      problems, including incorrect subsequent type species designations, also create
      uncertainty for many well-established genera. The advent of in situ studies in
      the 1970s revealed these issues; now molecular technology is again changing the
      taxonomic landscape. The competing methodologies involved must be seen in context
      if they are to avoid becoming an additional basis for continuing nomenclatorial
      instability. To prevent this happening, the International Commission on
      Zoological Nomenclature (ICZN) will need to focus on rules that consolidate well
      established nomenclature and allow for the designation of new type specimens that
      are unambiguous, and which include both skeletal material and soft tissue for
      molecular study. Taxonomic and biogeographic findings have now become linked,
      with molecular methodologies providing the capacity to re-visit past taxonomic
      decisions, and to extend both taxonomy and biogeography into the realm of
      evolutionary theory. It is proposed that most species will ultimately be seen as
      operational taxonomic units that are human rather than natural constructs, which
      in consequence will always have fuzzy morphological, genetic, and distribution
      boundaries. The pathway ahead calls for the integration of morphological and
      molecular taxonomies, and for website delivery of information that crosses
      current discipline boundaries.

PMID- 24459325
TI  - A Method for Choosing the Smoothing Parameter in a Semi-parametric Model for
      Detecting Change-points in Blood Flow.
AB  - In a smoothing spline model with unknown change-points, the choice of the
      smoothing parameter strongly influences the estimation of the change-point
      locations, and the function at the change-points. In a tumor biology example,
      where change-points in blood flow in response to treatment were of interest,
      choosing the smoothing parameter based on minimizing generalized cross
      validation, GCV, gave unsatisfactory estimates of the change-points. We propose a
      new method, aGCV, that re-weights the residual sum of squares and generalized
      degrees of freedom terms from GCV. The weight is chosen to maximize the decrease
      in the generalized degrees of freedom as a function of the weight value, while
      simultaneously minimizing aGCV as a function of the smoothing parameter and the
      change-points. Compared to GCV, simulation studies suggest that the aGCV method
      yields improved estimates of the change-point and the value of the function at
      the change-point.

PMID- 24459326
TI  - The phylogenetic information carried by a new set of morphological characters in
      planthoppers: the internal mouthpart structures and test in the Cixiidae model
      (Hemiptera: Fulgoromorpha).
AB  - Internal morphological structures of Cixiidae mouthparts are described and
      compared in various representatives of the Cixiidae and several other
      representatives of hemipterans. The morphological study shows that the mouthpart
      structures have not evolved uniformly and reveals the great disparity of these
      structures. Particularly, the connecting system of the mouthparts, localisation
      of salivary canal and shape of the mandibular and maxillar stylets provide
      together a new set of 17 new characters. A parsimonious analysis to evaluate the
      phylogenetic interest carried by these 17 selected characters shows that
      mouthpart structures have not evolved anarchically, but that they indeed carry
      some phylogenetic information that will be useful to be included in further
      morphological phylogenetic analysis.

PMID- 24459327
TI  - Validating the unequal-variance assumption in recognition memory using response
      time distributions instead of ROC functions: A diffusion model analysis.
AB  - Recognition memory z-transformed Receiver Operating Characteristic (zROC)
      functions have a slope less than 1. One way to accommodate this finding is to
      assume that memory evidence is more variable for studied (old) items than non
      studied (new) items. This assumption has been implemented in signal detection
      models, but this approach cannot accommodate the time course of decision making.
      We tested the unequal-variance assumption by fitting the diffusion model to
      accuracy and response time (RT) distributions from nine old/new recognition data
      sets comprising previously-published data from 376 participants. The eta
      parameter in the diffusion model measures between-trial variability in evidence
      based on accuracy and the RT distributions for correct and error responses. In
      fits to nine data sets, eta estimates were higher for targets than lures in all
      cases, and fitting results rejected an equal-variance version of the model in
      favor of an unequal-variance version. Parameter recovery simulations showed that
      the variability differences were not produced by biased estimation of the eta
      parameter. Estimates of the other model parameters were largely consistent
      between the equal- and unequal-variance versions of the model. Our results
      provide independent support for the unequal-variance assumption without using
      zROC data.

PMID- 24459328
TI  - Anti-inflammatory cytokine interleukin-4 inhibits inducible nitric oxide synthase
      gene expression in the mouse macrophage cell line RAW264.7 through the repression
      of octamer-dependent transcription.
AB  - Inducible nitric oxide synthase (iNOS) is a signature molecule involved in the
      classical activation of M1 macrophages and is induced by the Nos2 gene upon
      stimulation with Th1-cell derived interferon-gamma (IFNgamma) and bacterial
      lipopolysaccharide (LPS). Although the anti-inflammatory cytokine IL-4 is known
      to inhibit Nos2 gene expression, the molecular mechanism involved in the negative
      regulation of Nos2 by IL-4 remains to be fully elucidated. In the present study,
      we investigated the mechanism of IL-4-mediated Nos2 transcriptional repression in
      the mouse macrophage-like cell line RAW264.7. Signal transducer and activator of
      transcription 6 (Stat6) knockdown by siRNA abolished the IL-4-mediated inhibition
      of Nos2 induced by IFNgamma/LPS. Transient transfection of a luciferase reporter
      gene containing the 5'-flanking region of the Nos2 gene demonstrated that an
      octamer transcription factor (OCT) binding site in the promoter region is
      required for both positive regulation by IFNgamma/LPS and negative regulation by
      IL-4. Although IL-4 had no inhibitory effect on the DNA-binding activity of
      constitutively expressed Oct-1, IL-4-induced Nos2-reporter transcriptional
      repression was partially attenuated by overexpression of the coactivator CREB
      binding protein (CBP). These results suggest that a coactivator/cofactor that
      functionally interacts with Oct-1 is a molecular target for the IL-4-mediated
      inhibition of Nos2 and that IL-4-activated Stat6 represses Oct-1-dependent
      transcription by competing with this coactivator/cofactor.

PMID- 24459331
TI  - Live surgical workshops: Educational or vain glitz.

PMID- 24459329
TI  - Differential influence of inositol hexaphosphate on the expression of genes
      encoding TGF-beta isoforms and their receptors in intestinal epithelial cells
      stimulated with proinflammatory agents.
AB  - Transforming growth factor beta (TGF-beta) is a multifunctional cytokine
      recognized as an important regulator of inflammatory responses. The effect of
      inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the mRNA
      expression of TGF- beta1, TGF-beta2, TGF-beta3 and TbetaRI, TbetaRII, and
      TbetaRIII receptors stimulated with bacterial lipopolysaccharides (Escherichia
      coli and Salmonella typhimurium) and IL-1beta in intestinal cells Caco-2 for 3
      and 12 h was investigated. Real-time qRT-PCR was used to validate mRNAs level of
      examined genes. Bacterial endotoxin promoted differential expression of TGF-betas
      and their receptors in a time-dependent manner. IL-1beta upregulated mRNA levels
      of all TGF-betas and receptors at both 3 h and 12 h. IP6 elicited the opposed to
      LPS effect by increasing downregulated transcription of the examined genes and
      suppressing the expression of TGF- beta1 at 12 h. IP6 counteracted the
      stimulatory effect of IL-1beta on TGF-beta1 and receptors expression by
      decreasing their mRNA levels. IP6 enhanced LPS- and IL-1beta-stimulated mRNA
      expression of TGF-beta2 and -beta3. Based on these studies it may be concluded
      that IP6 present in the intestinal milieu may exert immunoregulatory effects and
      chemopreventive activity on colonic epithelium under inflammatory conditions or
      during microbe-induced infection/inflammation by modulating the expression of
      genes encoding TGF-betas and their receptors at transcriptional level.

PMID- 24459330
TI  - Proteinase-activated receptor-1 and immunomodulatory effects of a PAR1-activating
      peptide in a mouse model of prostatitis.
AB  - BACKGROUND: Nonbacterial prostatitis has no established etiology. We hypothesized
      that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We
      therefore investigated the effects of PAR1 stimulation in the context of a new
      model of murine nonbacterial prostatitis. METHODS: Using a hapten (ethanol
      dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild
      type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse
      prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on
      ethanol-DNBS-induced inflammation. RESULTS: Ethanol-DNBS-induced inflammation was
      maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the
      apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause
      inflammation, its coadministration with ethanol-DNBS reduced all indices of acute
      prostatitis. Further, PAR1-TF administration doubled the prostatic production of
      interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced
      IL-10 was not observed in PAR1-null mice and was not caused by the reverse
      sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also
      diminished ethanol-DNBS-induced inflammation in PAR1-null mice. CONCLUSIONS: PAR1
      is expressed in the mouse prostate and its activation by PAR1-TF elicits
      immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1
      TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by
      activating an as-yet unknown receptor.

PMID- 24459332
TI  - Dr. Anant Puranik: Sensitive, caring and generous to a fault.

PMID- 24459333
TI  - Treatment of unfavourable results of flexor tendon surgery: Ruptured repairs,
      tethered repairs and pulley incompetence.
AB  - As primary repair of divided flexor tendons becomes more common, secondary tendon
      surgery becomes largely that of the complications of primary repair, namely
      ruptured and adherent repairs. These occur with an incidence of each in most
      reported series world-wide of around 5%, with these problems having changed
      little in the last two decades, despite strengthening our suture repairs. Where
      the primary referral service is less well-developed, and as a more occasional
      occurrence where primary treatment is the routine, the surgeon faces different
      problems. Patients arrive at a hand unit variable, but longer, times after the
      primary insult, having had no, or bad, previous treatment. Sometimes the
      situation is the same, viz. an extended finger with no active flexion, but now no
      longer amenable to primary repair. Frequently, it is much more complex as a
      result of injuries to the other tissues of the digit and, also, as a result of
      the unaided healing process within the digit in the presence of an inactive
      flexor system. We present our experience in dealing with ruptured repairs,
      tethered repairs and pulley incompetence. 

PMID- 24459334
TI  - Necrotizing fasciitis.
AB  - Necrotizing fasciitis (NF) is among the most challenging surgical infections
      faced by a surgeon. The difficulty in managing this entity is due to a
      combination of difficulty in diagnosis, and also of early as well as late
      management. For the patient, such a diagnosis means prolonged hospital stay,
      painful dressings, an extended recovery, and in some unfortunate cases even loss
      of limb or life. Necrotizing fasciitis is a fairly common condition in surgical
      practice in the Indian context resulting in a fairly large body of clinical
      experience. This article reviews literature on MEDLINE with the key words
      "necrotizing," "fasciitis," and "necrotizing infections" from 1970, as well as
      from articles cross referenced therein. The authors attempt to draw comparisons
      to their own experience in managing this condition to give an Indian perspective
      to the condition. 

PMID- 24459335
TI  - Osteomas of the craniofacial region: A case series and review of literature.
AB  - OBJECTIVE: To discuss the clinical presentation, diagnosis and management of
      osteomas involving the craniomaxillofacial region. MATERIALS AND METHODS: This
      study was conducted from June 2004 to March 2012 at our institute. A total of 12
      cases between the ages of 10 and 50 years were managed with surgical excision and
      reconstruction. The criteria used to diagnose osteoma included radiographic and
      clinical features and histological confirmation of the specimen. The total follow
      up period ranged from 6 to 24 months. RESULTS: Out of 12 osteomas, 10 were
      peripheral and 2 were centrally located. Mandible involvement was seen in six
      patients, four involved the orbit, one the frontal bone and one the frontal bone
      with the skull base. All patients undergoing excision and reconstruction had a
      favourable aesthetic and functional outcome. There were no recurrences and no
      post-operative complications. CONCLUSION: Osteomas affect all age groups with no
      sex predilection and are usually clinically asymptomatic till they become large
      in size. Surgical excision and appropriate reconstruction is the mainstay of
      management. Surgery is indicated when lesion is symptomatic or actively growing
      and the surgical approach for exposure of the lesion should be case specific.

PMID- 24459336
TI  - Microsurgical reconstruction of major scalp defects following scalp avulsion.
AB  - INTRODUCTION: Total scalp avulsion is a serious injury, commonly occurring in
      Indian females working with industrial and agricultural machines. Their long
      hairs often get caught in a rapidly revolving machines, resulting in total
      avulsion of scalp. Lack of education and awareness in Indian villages often
      result in these patients coming late to the hospitals when replantation is not
      possible and scalp reconstruction remains the only available option. MATERIALS
      AND METHODS: We performed our study on 22 cases of scalp avulsion injury
      presented to us between June 2007 and April 2012 at Department of Burn, Plastic &
      Reconstructive Surgery, SMS Hospital, Jaipur. In all of them a free tissue
      transfer was performed as an elective procedure. RESULTS: Twenty two patients
      underwent free tissue transfer and followed up for an average period of 6 months.
      All patients included in this study were females with mean age of 28 yrs. Five
      patients in our study reported with partial necrosis of the free flaps which were
      subsequently managed with split-thickness skin graft (STSG). Two patients
      reported total necrosis of the flap which was re-operated using latissimus dorsi
      along with serratus anterior muscle (LDSA) from the contralateral side.
      CONCLUSION: As scalp avulsion because of rapidly rotating machine leads to large
      size defect not amenable for local tissue reconstruction. We performed
      reconstruction using LDSA and omental free flaps with split thickness skin graft
      (STSG) for large scalp defect and achieved good and stable soft tissue cover with
      satisfactory cosmesis.

PMID- 24459337
TI  - The use of the temporoparietal fascia flap in various clinical scenarios: A
      review of 71 cases.
AB  - OBJECTIVE: This report details our experience with the use of the temporoparietal
      fascia flap in different scenarios of reconstruction and to discuss our technique
      of harvest, clinical applications, and review of literature of this versatile
      flap. MATERIALS AND METHODS: A retrospective study of 82 cases of temporoparietal
      fascia flap in 71 patients, operated over a period of 10 years was conducted.
      Patients were grouped based on various clinical indications. The follow up period
      ranged from a minimum of 1 to a maximum of 10 years (Mean-four and a half years).
      All patients were analyzed for functional and aesthetic outcome using
      preoperative and postoperative photographs. RESULTS: No significant complications
      were seen in our series. Only 2 out of 82 flaps had partial necrosis of flap
      (2.44%). Two patients who were operated for release of submucous fibrosis
      developed recurrence due to continued use of tobacco. The final outcome in one
      patient of ear reconstruction was unsatisfactory due to flap failure. The
      remaining patients had satisfactory functional and aesthetic outcomes (95.77%).
      None had other complications like temporal branch of facial nerve injury or
      alopecia along the scar line. CONCLUSION: The TPFF is one of the most reliable
      and versatile flap in the head and neck region. It can also be reliably used as
      free fascial flap. When its advantages are combined with the surgeon's
      resourcefulness, various defects can be successfully reconstructed using the
      temporoparietal facia flap with satisfactory aesthetic and functional outcome.

PMID- 24459338
TI  - Efficacy of communication amongst staff members at plastic and reconstructive
      surgery section using smartphone and mobile WhatsApp.
AB  - OBJECTIVE: The objective of this study is to assess the efficacy of smartphone
      and its WhatsApp application as a communication method amongst the staff of
      plastic and reconstructive surgery section at tertiary care health facility.
      MATERIALS AND METHODS: From January 2012 onwards, the authors used smartphones
      and its WhatsApp application as a communication method amongst their team for
      various aspects of patient management and as a tool for academic endorsements.
      RESULTS: During the period of this study, there were 116 episodes regarding
      patient management, which were handled, in a timely fashion by using this
      application. In addition opinion of rotating residents in the section was sought
      regarding the efficacy of this method of communication. Overall majority of
      residents were satisfied with this mode of communication. CONCLUSIONS: This new
      method of communication is an effective method for clinical and academic
      endorsements. The method is cheap and quick and easy to operate.

PMID- 24459339
TI  - Efficacy of communication amongst staff members at plastic and reconstructive
      surgery section using smartphone and mobile Whats App.

PMID- 24459340
TI  - The effect of different positions on lower limbs skin perfusion pressure.
AB  - We have encountered situations of patients with critical limb ischemia
      accompanied by pain at rest and necrosis, who hang their legs down from the bed
      during sleep. This lower limb position is known to be a natural position, which
      reduces pain in the lower extremity induced by ischemia. However, the effect of
      this position on blood flow of the lower extremity is poorly understood. We
      studied whether measurements of skin perfusion pressure (SPP) changes by leg
      position and the difference between healthy adults and patients with critical
      limb ischemia. The subjects of this study were 10 healthy adults and 11 patients
      with critical limb ischemia. Patients with critical limb ischemia, including both
      dorsum of foot and plantar of foot, having SPP of lower limbs of less than 40
      mmHg (supine position) were the object of this study. SPP was measured on four
      positions (supine position, lower limbs elevation position, sitting position, and
      reclining bed elevation of 20( degrees ) position). In sitting position, both the
      number of healthy adults and critical patients show significant increases in SPP
      compared with the other three positions. These results suggest that sitting
      position is effective to keep good blood stream of lower limbs not only in
      healthy adults but also in patients with critical limb ischemia. However, an
      appropriate leg position should not have lower limbs hang downwards for long
      periods time because edema is caused by the fall in venous return in lower limbs,
      and the wound healing is prolonged. Our clinical research could be more useful in
      the future, particularly in developing countries, for surgeons managing wounds in
      leg and foot and preserving ischemic limbs. 

PMID- 24459341
TI  - Aesthetical outcome after breast reconstruction using deep inferior epigastric
      perforator flap: Personal techniques.
AB  - BACKGROUND: Now-a-days, deep inferior epigastric perforator (DIEP) flap breast
      reconstruction is widespread throughout the world. The aesthetical result is very
      important in breast reconstruction and its improvement is mandatory for plastic
      surgeons. MATERIALS AND METHODS: The most frequent problems, we have observed in
      breast reconstruction with DIEP flap are breast asymmetry in terms of volume and
      shape, the bulkiness of the inferior lateral quadrant of the new breast, the loss
      of volume of the upper pole and the lack of projection of the inferior pole. We
      proposed our personal techniques to improve the aesthetical result in DIEP flap
      breast reconstruction. Our experience consists of more than 220 DIEP flap breast
      reconstructions. RESULTS: The methods mentioned for improving the aesthetics of
      the reconstructed breast reported good results in all cases. CONCLUSION: The aim
      of our work is to describe our personal techniques in order to correct the
      mentioned problems and improve the final aesthetical outcome in DIEP flap breast
      reconstruction.

PMID- 24459342
TI  - Dental impression compound as an effective splint for maintenance of ear
      elevation in microtia reconstruction.
AB  - Ear projection is an important goal to be achieved after stage two (ear
      elevation) in cases of microtia. This is a retrospective study conducted on
      patients with microtia who underwent staged reconstruction for the same. This
      study has been carried out over a period of 10 years with 211 patients. Dental
      impression compound was used as a splint after ear elevation and split skin
      grafting to maintain the projection of the ear. Projection of the ear was
      measured both pre- and post-procedure and at every follow-up using goniometer and
      photographic documentation was simultaneously done. Statistical analysis was
      performed using t-test. Patients were reviewed every month and splint was
      continued until 6 months post-surgery. The splint was very effective in
      maintaining the ear projection of more than 20( degrees ) even after prolonged
      follow-up of upto 2 years. There were no complications associated with the splint
      application or prolonged use. 

PMID- 24459343
TI  - Facial contour deformity correction with microvascular flaps based on the 3
      dimentional template and facial moulage.
AB  - INTRODUCTION: Facial contour deformities presents with varied aetiology and
      degrees severity. Accurate assessment, selecting a suitable tissue and
      sculpturing it to fill the defect is challenging and largely subjective.
      Objective assessment with imaging and software is not always feasible and
      preparing a template is complicated. A three-dimensional (3D) wax template pre
      fabricated over the facial moulage aids surgeons to fulfil these tasks. Severe
      deformities demand a stable vascular tissue for an acceptable outcome. MATERIALS
      AND METHODS: We present review of eight consecutive patients who underwent
      augmentation of facial contour defects with free flaps between June 2005 and
      January 2011. De-epithelialised free anterolateral thigh (ALT) flap in three,
      radial artery forearm flap and fibula osteocutaneous flap in two each and groin
      flap was used in one patient. A 3D wax template was fabricated by augmenting the
      deformity on facial moulage. It was utilised to select the flap, to determine the
      exact dimensions and to sculpture intraoperatively. Ancillary procedures such as
      genioplasty, rhinoplasty and coloboma correction were performed. RESULTS: The
      average age at the presentation was 25 years and average disease free interval
      was 5.5 years and all flaps survived. Mean follow-up period was 21.75 months. The
      correction was aesthetically acceptable and was maintained without any recurrence
      or atrophy. CONCLUSION: The 3D wax template on facial moulage is simple,
      inexpensive and precise objective tool. It provides accurate guide for the
      planning and execution of the flap reconstruction. The selection of the flap is
      based on the type and extent of the defect. Superiority of vascularised free
      tissue is well-known and the ALT flap offers a versatile option for correcting
      varying degrees of the deformities. Ancillary procedures improve the overall
      aesthetic outcomes and minor flap touch-up procedures are generally required.

PMID- 24459344
TI  - Gross anatomy of superficial fascia and future localised fat deposit areas of the
      abdomen in foetus.
AB  - BACKGROUND: The development and popularity of body contouring procedures such as
      liposuction and abdominoplasty has renewed interest in the anatomy of the
      superficial fascia and subcutaneous fat deposits of the abdomen. The study of
      anatomy of fascia and fetal adipose tissue was proposed as it may be of value in
      understanding the possible programing of prevention of obesity. OBJECTIVES: The
      present study was undertaken to understand the gross anatomy of superficial
      fascia of abdomen and to study the gross anatomy of future localized fat deposits
      (LFDs) area of abdomen in fetus. MATERIALS AND METHODS: Four fetus (two male &
      two female) of four month of intrauterine life were dissected. Attachments &
      layers of superficial fascia and future subcutaneous fat deposit area of upper
      and lower abdomen were noted. RESULTS: Superficial fascia of the abdomen was
      multi layered in mid line and number of layers reduced laterally as in adult. The
      future abdominal LFD (localized fat deposits) area in fetus shows brownish-white
      blubbary tissue without well-defined adult fat lobules. CONCLUSION: The
      attachment and gross anatomy of superficial fascia of the fetus was similar to
      that in adults. The future LFD areas showed brownish white blubbary tissue with
      ill-defined fat lobules.

PMID- 24459345
TI  - Augmentation rhinoplasty with custom-made S-shape silicone implant in Asians: A
      15-year experience.
AB  - BACKGROUND: Asians have low nasal dorsum, thick skin envelope, low defined alar
      cartilage, low projection of nasal tip and broad alar base. Augmentation
      rhinoplasty with silicone prosthesis has been performed with predictable results,
      but unfavourable results and complications still present. This series show
      techniques and results from single surgeon experience. MATERIALS AND METHODS: We
      retrospectively reviewed 548 patients chart during January 1995 to December 2009.
      All patients underwent custom-made S-shape implant silicone augmentation
      rhinoplasty operated by a single surgeon. There were three major operative steps:
      (1) Intra-operative S-shape implant carving; (2) pocket dissection through
      bilateral rim incision and (3) tension adjustment before closure. All the
      patients were recorded for early surgical complications and satisfaction.
      RESULTS: There were 519 women and 29 men. The mean age is 25.5 years (18-56
      years). Mean follow-up period was 6 months (1-60 months). The majority of patient
      were appointed for esthetic augmentation (86.8%). 515 cases (94.9%) showed well
      satisfaction following the operation. The total complication rate was 6.5% (4.9%
      deviation, 0.7% extrusion, 0.5% hematoma and 0.3% infection). All the
      complications were corrected with uneventful sequelae. CONCLUSION: Augmentation
      rhinoplasty with custom-made S-shape silicone implant by closed approach provides
      high satisfaction with acceptable early complication rate.

PMID- 24459346
TI  - Treatment of non-healing sternum wound after open-heart surgery with allogenic
      platelet-rich plasma and fibrin glue-preliminary outcomes.
AB  - INTRODUCTION: Non-healing wound in the sternal region after coronary arteries
      bypass graft surgery is a serious complication. For healing a chronic wound,
      several novel approaches have been proposed recently such as using bone marrow
      stem cells, platelets and fibrin glue (PFG); but a non-invasive method is highly
      desirable in the first approach for treatment. The current study was undertaken
      to evaluate the effect of the combination of PFG in one treatment. MATERIALS AND
      METHODS: We report on the treatment of six patients with life-threatening chronic
      sternum wounds, which caused septicemia with multi-drug resistant pathogens. The
      ulcers were extensively debrided initially and were measured and photographed at
      weekly intervals. The combination of PFG was applied topically on the wound after
      every 2 days. RESULTS: The wounds were completely closed in five patients and
      significantly reduced in size in one. There was no evidence of local or systemic
      complications and any abnormal tissue formation, keloid or hypertrophic scarring.
      CONCLUSIONS: Our study suggests, in the first approach, PFG can be used safely in
      order to heal a non healing sternum wound following coronary artery bypass
      surgery.

PMID- 24459347
TI  - Reconstruction of post-traumatic long bone defect with vascularised free fibula:
      A series of 28 cases.
AB  - INTRODUCTION: The severe long bone defects usually follow high-energy trauma and
      are often associated with a significant soft-tissue injury. The goal of
      management of these open long bone defects is to provide stable fixation with
      maintenance of limb length and soft-tissue coverage. The purpose of this article
      is to present the clinic-radiological outcome, complications and treatment of
      post-traumatic long bone defect with vascularised fibula transfer. MATERIALS AND
      METHODS: Retrospective records of 28 patients were analysed who presented with
      post-traumatic long bone defects and in whom reconstruction with vascularised
      free fibula was done. Demographic data were recorded and clinical and
      radiological assessment was done. RESULTS: Out of 28 patients in whom
      vascularised free fibula transfer was carried out three flaps were lost while non
      union occur in three patients. Three patients developed a stress fracture of
      transferred free fibula in the post-operative period. Few of the patients
      experienced some problems in the donor leg; however, all of them improved in
      subsequent follow-up. DISCUSSION: It is clearly evident from this study that
      timing of surgery plays an important role in the micro-vascular reconstruction in
      trauma cases. All the complication like flap loss, non-union or delayed union
      occur in patients in whom reconstruction was delayed. CONCLUSION: The free
      vascularised fibula graft is a viable method for the reconstruction of skeletal
      defects of more than 6 cm, especially in cases of scarred and avascular recipient
      sites or in patients with combined bone and soft-tissue defects. Results are best
      when the reconstruction is done within 1 week of trauma.

PMID- 24459348
TI  - A retrospective analysis of early experience with modified complete primary
      repair of exstrophy bladder (CPRE) in neonates and children.
AB  - OBJECTIVE: To study the problems faced during the surgery and follow-up of
      modified complete primary repair of exstrophy (CPRE) technique. Initial
      experience with CPRE and its short- and long-term outcomes with respect to
      continence status and psychosocial impact are reported. MATERIALS AND METHODS: A
      retrospective review of the hospital case records from March 2008 to September
      2012 was performed. Data of patients with bladder exstrophy managed by a single
      paediatric surgeon using modified CPRE technique were analysed. Quality of life
      and psychosocial impact of the surgery were assessed using Pediatric Quality of
      Life Inventory (PedsQL 4.0) and compared with those of typical peers. RESULTS:
      Eight children (age 4 days-12 years) underwent CPRE using modified Mitchell's
      technique. Two patients (25%) experienced early postoperative complications, with
      infection and fistula developing in one each. All the patients were doing well on
      follow-up, with variable continence rates and good cosmesis. Mean duration of
      follow-up was 18.5 months (range 6 months-4 years). Five out of seven (71%)
      children were continent or partially continent. One case was lost to follow-up.
      PedsQL scores were comparable with those of age-matched peers in all domains
      except the social functioning domain in 8-12 years age group (83.53 +/- 9.70 vs.
      77.86 +/- 10.22, P < 0.05). CONCLUSION: Our preliminary results with modified
      CPRE in neonates and children have been encouraging. No major complications were
      observed. Continence rate was satisfactory and cosmetic results were good. Though
      the technique is being practiced at several Indian centres, there is a paucity of
      comprehensive Indian data on CPRE.

PMID- 24459349
TI  - Functional outcome of patients undergoing replantation of hand at wrist level-7
      year experience.
AB  - BACKGROUND: Replantation is defined as reattachment of amputated limb using
      neurovascular and musculoskeletal structures in order to obtain recovery of limb.
      Re-vascularisation involves all the above steps in case of limb injuries that
      result in a near total amputation. AIM AND OBJECTIVE: To study the functional
      outcome of patients undergoing replantation of hand at wrist level. MATERIAL AND
      METHODS: This is a retrospective study of patients who underwent replantation of
      total amputation of hand at wrist level within a period of Jan 2003-June 2010. We
      evaluated post operative functional outcome compared to uninjured hand taking
      into consideration: 1. The patient's overall satisfaction with the hand. 2.
      Recovery of flexor and extensor function of thumb and fingers. 3. Recovery of
      thumb opposition. 4. Recovery of sensations in the median and ulnar nerve
      distribution. 5. Ability of surviving hand to perform daily tasks. RESULTS: There
      were total seventeen patients and age range was two years to 55 years. Out of 17
      patients,16 were males. All the replantations were successful except for one.
      SUMMARY: The results showed that, although the replanted hands were never
      functionally as good as the contralateral hand the patients were able to perform
      most of the daily activities.

PMID- 24459350
TI  - Facial contouring with parascapular free flap: A case series of 22 cases.
AB  - BACKGROUND: The facial asymmetry correction in complex craniofacial malformations
      presents a challenging problem for reconstructive surgeons. Progressive
      hemifacial atrophy (HFA) and hemifacial microsomia (HFM) can manifest in
      different grades of severity. Most patients require only soft-tissue
      augmentation. Free flaps are the best option for correction of severe facial soft
      tissue deficiency. MATERIALS AND METHODS: Twenty-two patients of HFM and HFA were
      included in this study from January 2006 to March 2009 in the Department of
      Plastic and Reconstructive Surgery, SMS Medical College and Hospital. In all
      cases, atrophy correction was done using de-epithelialised parascapular free flap
      with the de-epithelialised surface was placed under the skin. A small skin paddle
      was taken for monitoring. RESULTS: All cases were reconstructed with de
      epithelialised parascapular free flap. There was no flap loss in this series.
      Hematoma was noted in five cases. Debulking and removal of skin paddle were done
      in all cases after 6 months. Atrophy recurrence was not observed in any of the
      cases on follow-up. CONCLUSION: Contouring of face in cases of HMF and HFA is
      satisfactorily done with the parascapular free flap. It gives better cosmetic
      results with minimal donor site morbidity. Facial vessels are better recipient
      vessels for anastomosis. Keeping de-epithelialised surface of flap under the skin
      helped in preventing sagging.

PMID- 24459351
TI  - Double flap from amputated opposite lower limb for cover of plantar and dorsal
      surfaces of a crushed foot.
AB  - Bilateral limb trauma poses many possibilities for management. In a situation of
      bilateral amputation, if the amputated limb is not salvageable or replantation is
      not advisable, the amputated limb can be used to harvest tissue for free tissue
      transfer to cover the amputation stump. We describe a case here in which we have
      used these principles. 

PMID- 24459352
TI  - Short-term augmentation of venous drainage with extra-corporeal shunt and
      simultaneous auto-transfusion, for salvaging a congested free flap.
AB  - Adequate drainage of venous blood is the most critical part of successful free
      tissue transfer. We report a case of anterolateral thigh flap used for covering
      open communited tibial fracture. The flap was salvaged with short term
      augmentation of venous drainage with external shunt. The drainage was continued
      for six days. It was confirmed that there is no more congestion after blocking
      the catheter and then the drainage was discontinued on seventh day. The flap was
      successfully salvaged. This method has potential applications in multiple
      situations for successful salvage of free tissue transfer. 

PMID- 24459353
TI  - Touraine Solente Gole syndrome: The elephant skin disease.
AB  - Touraine Solente Gole syndrome is a rare hereditary syndrome of primary
      pachydermoperiostosis, with the characteristic triad of pachydermia (or elephant
      like skin), periostosis and acropachia. A 27-year-old patient presented with
      aesthetic deformity of forehead due to deep skin folds and coarsening of facial
      features due to progressive thickening of skin. Associated palmoplantar
      hyperkeratosis with broadened of finger and toe tips and digital clubbing were
      noticed. Dermatologic evaluation revealed cutis verticis gyrata of scalp,
      seborrhoeic hyperplasia of face and hyperhidrosis. Natural history of the disease
      and aetiopathogenesis were reviewed. Aesthetic correction of forehead through
      frontal rhytidectomy was attempted. 

PMID- 24459354
TI  - Total upper and lower eyelid reconstruction using deltopectoral flap.
AB  - Total upper and lower eyelid unilateral full thickness reconstruction is a
      surgical challenge. A case of right orbital haemangioma with unilateral complete
      defect of total upper and lower eyelids with right orbital exenteration is
      reported, together with the surgical technique of reconstruction. Patient was a
      24-year-old female who underwent right orbital exenteration with total upper and
      lower eyelid excision for orbital haemangioma presented after 3 weeks of the
      above procedure. In the first stage split thickness skin grafting is used to
      resurface orbital cavity raw area followed by staged reconstruction of total
      upper and lower eyelid reconstruction using pedicle deltopectoral flap. This
      reconstruction provided stable eyelid reconstruction to retain ocular prosthesis
      with concealed and minimal donor area. After reconstruction patient underwent
      rehabilitation with ocular prosthesis, now the patient is satisfied with
      cosmetically acceptable results. 

PMID- 24459355
TI  - Infrared venography of the hand in Apert syndrome.
AB  - As well as craniofacial synostosis, complex syndactyly of hands is a distinctive
      feature of Apert syndrome. Consideration of blood flow to the digits is very
      important in separation surgery. Several reports offer information about arterial
      distribution in Apert's hands. Though, venous pattern has not been well
      discussed. Infrared venography offers a real-time image with minimal invasion. An
      Apert syndrome patient underwent a series of finger splitting surgeries. Infrared
      venography was carried out to assess veins. There was a palmar venous arch,
      placing distally to the metacarpophalangeal joint. The arch had to be cut to
      divide fused fingers sufficiently. As well as arterial abnormality, venous
      uniqueness should be noted in Apert syndactyly surgeries. Infrared venography,
      which can be carried out easily, offers good information that surgeon require. 

PMID- 24459356
TI  - Electrical burns of the abdomen.
AB  - A 35-year-old male farmer came in contact with 11,000 volts high tension electric
      wire and sustained full thickness burn wounds over scapula, upper limb and
      anterior abdominal wall along with perforation of the intestine. Patient was
      initially managed conservatively in general surgery ward and was referred to us
      after 3 days with necrosis of the burned skin and muscles over the shoulder and
      abdomen. Patient was initially managed conservatively and then thorough
      debridement of the necrotic skin over the left shoulder and upper arm was done
      and the area was split skin grafted. Patient developed enterocutaneous fistula,
      which healed over a period of 8 weeks. The granulating wound over the abdomen was
      also skin grafted and patient was discharged after 18 days. About 4 months, after
      the discharge patient presented with ventral hernia. Repair of ventral hernia by
      synthetic mesh application and reconstruction of the abdominal wall with a free
      tensor fascia lata flap was done over the mesh, but the flap failed. Then after
      debridement two random pattern transposition skin flaps, one from the right upper
      and another from the left lower abdomen were transposed over the abdominal wound
      and donor area was skin grafted. Patient was discharged after 17 days. 

PMID- 24459357
TI  - 'Biaxial serial excision' or 'polyaxial serial excision'.

PMID- 24459358
TI  - Use of 'reverse prints', 'mirror image' or 'horizontal flip' in ear
      reconstruction.

PMID- 24459359
TI  - Safe and versatile variation of the surgical technique for treating the
      underdeveloped antihelix in otoplasty.

PMID- 24459360
TI  - A novel technique for piercing of ear lobule suited to Indian subcontinent.

PMID- 24459361
TI  - Spreadsheet software to assess the locomotor disability: Submitting the actual
      software.

PMID- 24459362
TI  - A simple method of unblocking the liposuction cannula.

PMID- 24459363
TI  - Stockinette sling: 'A simple method and patient friendly method of immobilisation
      of elbow and shoulder after a free functioning muscle transfer in global brachial
      plexus palsy'.

PMID- 24459364
TI  - Successful thrombolytic therapy for massive pulmonary embolism following
      abdominoplasty.

PMID- 24459365
TI  - Personality pathways of successful ageing.

PMID- 24459366
TI  - Stress and periodontal disease: The link and logic!!
AB  - Stress is an equated response to constant adverse stimuli. At one point or
      another everybody suffers from stress. Stress is compatible with good health,
      being necessary to cope with the challenges of everyday life. Problems start when
      the stress response is inappropriate to the intensity of the challenge.
      Psychological stress can down regulate the cellular immune response.
      Communication between the central nervous system and the immune system occurs via
      a complex network of bidirectional signals linking the nervous, endocrine, and
      immune systems. Stress disrupts the homeostasis of this network, which in turn,
      alters immune function. Direct association between periodontal disease and stress
      remains to be proven, which is partly due to lack of an adequate animal models
      and difficulty to quantifying the amount and duration of stress and also there
      are many factors influencing the incidence and severity of periodontal disease.
      Nevertheless, more recent studies indicate that psychosocial stress represents a
      risk indicator for periodontal disease and should be addressed before and during
      treatment. This paper discusses how stress may modulate host response to bacteria
      and influence the course and progression of periodontal disease. 

PMID- 24459367
TI  - Demographic and clinical profile of substance abusing women seeking treatment at
      a de-addiction center in north India.
AB  - BACKGROUND: In the recent decades increasing number of women have been seeking
      deaddiction services. Despite that the report data is very limited from India.
      OBJECTIVES: The present research aimed to study the demographic and clinical
      profile of women seeking deaddiction treatment at a tertiary care center in North
      India. MATERIALS AND METHODS: Retrospective structured chart review of 100 women
      substance abusers seeking treatment at a deaddiction center between September
      1978 and December 2011. RESULTS: A typical case was of 36.3 years age, married
      (65%), urban (61%), nuclear family (59%) based housewife (56%), with good to fair
      social support (69%). The commonest substance of abuse was tobacco (60%),
      followed by opioids (27%), alcohol (15%), and benzodiazepines (13%). The common
      reasons for initiation of substance use were to alleviate frustration or stress
      (49%) and curiosity (37%). Family history of drug dependence (43%), comorbidity
      (25%), and impairments in health (74%), family (57%), and social domains (56%)
      were common. Only a third of the sample paid one or more follow visit, and of
      those 58% were abstinent at the last follow-up. Significant predictors identified
      were being non-Hindu and higher educational years for abstinent status at follow
      up. CONCLUSION: The common substances of abuse were tobacco, opioids, and alcohol
      and benzodiazepines; and family history of drug abuse and comorbidity were
      common. The follow-up and outcome were generally poor. This profile gives us some
      clues to address a hidden health problem of the community.

PMID- 24459368
TI  - Socio-demographic and clinical predictors of absenteeism - A cross-sectional
      study of urban industrial employees.
AB  - CONTEXT: Public sector undertakings are facing a threat of privatization due to
      unsatisfactory performance putting pressure on management and in turn to
      employees. There is an increasing trend of absenteeism observed amongst employees
      citing job stress. AIM: To find an association between job stress and absenteeism
      in relation to socio-demographic and clinical profile. MATERIALS AND METHODS: The
      study was conducted in an urban aeronautical industry with 68 employees who
      mentioned stress at workplace during evaluation. Job stress was assessed using
      Professional Life Stress Scale (David Fontana). Those who scored more than 30 (n
      = 43) were taken up for the study after an informed consent. A semi-structured
      questionnaire was administered to find socio-demographic and clinical profile.
      Employees who reported taking leave in last six months just to avoid work or
      workplace constitute the "absenteeism" group. The absenteeism group was compared
      to non-absenteeism group using Fisher exact/Chi-square test or independent t-test
      depending on type of variables. RESULTS: Out of 43 subjects, 18 had absenteeism
      while 25 did not have absenteeism. Comparing the two groups, interstate
      migration, having more than one previous job, commuting time more than an hour,
      co-morbid anxiety/depression, and alcohol abuse were significantly associated
      with absenteeism (P < 0.05). Absentees complained more about fatigue and
      relationship problem with colleagues than non-absentees (P < 0.05). Factors like
      age, sex, marital status, education, gross pay, job tenure, past or family
      history of psychiatry illnesses had no significant association with absenteeism
      (P > 0.05). CONCLUSION: In absenteeism research, one of the widely accepted
      models is Steer and Rhode's "Process model of absenteeism." The model postulates
      job stress as one of the barriers for attendance. Thus, knowing the factors for
      absenteeism would help in preventing absenteeism.

PMID- 24459369
TI  - Impacts of mustard gas exposure on veterans mental health: A study on the role of
      education.
AB  - BACKGROUND: The mustard gas (MG) exposure can impair physical health and
      therefore increase the probability of the posttraumatic stress disorder (PTSD)
      and psychological disorders. AIM: The aim of this study was to investigate long
      term effects of MG exposure on veterans' mental health. MATERIALS AND METHODS:
      This was a cross-sectional study. In order to assess prevalence of mental health
      and PTSD of 100 MG victims 25 years after the exposure to MG in Iran-Iraq
      conflict, the general health questionnaire (GHQ-28) and Impact of Event Scale
      Revised, respectively was administered. RESULTS: The mean (+/-standard deviation
      (SD)) age of participants was 40.63 (+/-5.86) years. The mean GHQ-28 (47.34) of
      the study group was higher compared to standardized cutoff point (23) of the
      Iranian community. Also, it was found that 38 participants (38%) suffer from
      PTSD. The results of this study showed that academic education in the PTSD group
      was less than that in the non-PTSD group (P=0.03). In addition, in multivariate
      analysis it was found that only education level of the veterans and their wives
      were effective on the mental health score (adjusted P=0.036 and 0.041,
      respectively). The mean score of depression and psychosocial activity subscale in
      patients at higher education level was lower than patients at lower education
      level (P<0.05). CONCLUSION: This study found that sulfur mustard (SM) exposure
      can be effect on mental health even 25 years after exposure. Therefore, the
      psychological state should be more considered in chemical injured veterans and it
      is important that providing more mental health centers for this community.

PMID- 24459370
TI  - Psychological vulnerability, burnout, and coping among employees of a business
      process outsourcing organization.
AB  - BACKGROUND: The business process outsourcing (BPO) sector is a contemporary work
      setting in India, with a large and relatively young workforce. There is concern
      that the demands of the work environment may contribute to stress levels and
      psychological vulnerability among employees as well as to high attrition levels.
      MATERIALS AND METHODS: As part of a larger study, questionnaires were used to
      assess psychological distress, burnout, and coping strategies in a sample of
      1,209 employees of a BPO organization. RESULTS: The analysis indicated that 38%
      of the sample had significant psychological distress on the General Health
      Questionnaire (GHQ-28; Goldberg and Hillier, 1979). The vulnerable groups were
      women, permanent employees, data processors, and those employed for 6 months or
      longer. The reported levels of burnout were low and the employees reported a
      fairly large repertoire of coping behaviors. CONCLUSIONS: The study has
      implications for individual and systemic efforts at employee stress management
      and workplace prevention approaches. The results point to the emerging and
      growing role of mental health professionals in the corporate sector.

PMID- 24459371
TI  - Catatonia: Etiopathological diagnoses and treatment response in a tertiary care
      setting: A clinical study.
AB  - AIM: Catatonia is caused by a variety of psychiatric and organic conditions. The
      onset, clinical profile, and response to treatment may vary depending on the
      underlying cause. The study is an attempt to explore clinical profile, possible
      etiological correlates with neurotic/psychotic spectrum illnesses, and response
      to treatment and outcome in patients of catatonia. MATERIALS AND METHODS:
      Retrospective chart analysis by using semistructured data sheet for the analysis
      of sociodemographic data, clinical profile, precipitating event, and response to
      treatment in patients with catatonic symptoms admitted to IHBAS (Institute of
      Human Behaviour and Allied Sciences, New Delhi, India) from January 2009 to
      December 2010 was undertaken. RESULTS: Catatonia was commonly observed in
      patients with the following profile - late twenties, female, Hindu religion,
      urban background, and housewives. Psychotic spectrum disorder (57%, N=35) was the
      most commonly entertained diagnosis and affective disorder (18%, N=11) being the
      second common. Thirty four percent of the subjects responded to lorazepam
      treatment and rest required modified electroconvulsive therapy (MECT).
      CONCLUSION: Catatonia is more likely to be associated with Schizophrenia and
      Other Psychotic Disorders in Indian settings. Majority of patients responded to
      therapy either by lorazepam alone or to its augmentation with modified ECT. The
      study being a retrospective one, the sample being representative of the treatment
      seeking group only, and unavailability of the follow up data were the limitations
      of the study.

PMID- 24459372
TI  - Depression during pregnancy: Prevalence and obstetric risk factors among pregnant
      women attending a tertiary care hospital in Navi Mumbai.
AB  - CONTEXT: Depression affects about 20% of women during their lifetime, with
      pregnancy being a period of high vulnerability. Prevalence of depression during
      pregnancy ranges from 4% to 20%. Several risk factors predispose to depression
      during pregnancy including obstetric factors. Depression during pregnancy is not
      only the strongest risk factor for post-natal depression but also leads to
      adverse obstetric outcomes. AIMS: To study the prevalence of depression during
      pregnancy and its associated obstetric risk factors among pregnant women
      attending routine antenatal checkup. SETTINGS AND DESIGN: Cross-sectional
      observational survey done at the outpatient department (OPD) of the department of
      obstetrics of a tertiary care hospital in Navi Mumbai. MATERIALS AND METHODS: One
      hundred and eighty-five pregnant women were randomly administered the Beck
      Depression Inventory (BDI) for detecting depression. Additional socio-demographic
      and obstetric history was recorded and analyzed. RESULTS: Prevalence of
      depression during pregnancy was found to be 9.18% based upon BDI, and it was
      significantly associated with several obstetric risk factors like gravidity (P =
      0.0092), unplanned pregnancy (P = 0.001), history of abortions (P = 0.0001), and
      a history of obstetric complications, both present (P = 0.0001) and past (P =
      0.0001). CONCLUSIONS: Depression during pregnancy is prevalent among pregnant
      women in Navi-Mumbai, and several obstetric risk factors were associated to
      depression during pregnancy. Future research in this area is needed, which will
      clearly elucidate the potential long-term impact of depression during pregnancy
      and associated obstetric risk factors so as to help health professionals identify
      vulnerable groups for early detection, diagnosis, and providing effective
      interventions for depression during pregnancy.

PMID- 24459373
TI  - Quality of life as an outcome measure in the treatment of alcohol dependence.
AB  - BACKGROUND: Quality of life has emerged as an important treatment outcome measure
      for alcohol dependence whose natural course comprises of remission and relapse.
      MATERIALS AND METHODS: The purpose of this study was to examine the prospective
      change in Quality of life (QoL) in 56 patients aged 18-45 years of alcohol
      dependence over a three months' period and compare it with QoL of 150 age- and
      gender- matched healthy controls using WHOQoL-BREF. Severity of alcohol
      dependence and drinking parameters were assessed. RESULTS: Significant
      improvement in QoL of patients of alcohol dependence over three months'
      abstinence. The physical, psychological, social, and environment domains of QoL
      in alcohol dependence subjects were significantly lower before treatment
      initiation than the healthy controls. Alcoholic liver disease emerged as a
      predictor of improvement in psychological and social domains of QoL. CONCLUSION:
      The study confirms poor quality of life in patients of alcohol dependence before
      intervention. The regular follow-up with the family members in out-patient
      setting enables the patients achieve complete abstinence, thereby improving their
      quality of life.

PMID- 24459374
TI  - Cognitive function in schizophrenia and its association with socio-demographics
      factors.
AB  - BACKGROUND: Schizophrenia is a chronic and debilitating psychiatric illness
      consisting primarily of positive and negative symptoms. However, cognitive
      deficits in various domains have been consistently replicated in patients with
      schizophrenia. Therefore, the present study was designed to assess cognitive
      impairment in schizophrenia and to correlate the same with sociodemographic
      factors. MATERIALS AND METHODS: Cognitive function in 100 patients with
      schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, Text Revision (DSM IV-TR) criteria attending the psychiatry
      outpatient department (OPD) of Department of Psychiatry, SBKS MIRC was assessed
      using Addenbrooke's Cognitive Examination Revised (ACER) rating scale and Mini
      Mental State Examination (MMSE) and sociodemographic details was obtained using
      semistructured proforma. Data was analyzed by Chi-square and t-test. RESULTS:
      About 70% patients of schizophrenia were found to have cognitive dysfunction for
      attention, concentration, memory, language, and executive function. Positive
      symptoms were associated with memory (P<0.001) and attention impairment (P<0.05).
      Patients with duration of illness >2 years and belonging to urban habitat showed
      more cognitive dysfunction. Male patients were associated with impairment in two
      domains of ACER: Language and memory. CONCLUSION: The study findings depict that
      persistent cognitive deficits are seen in patients with schizophrenia. Its
      correlation with sociodemographic factors showed that patients with >2 years of
      illness and belonging to urban habitat showed more cognitive dysfunction. Male
      patients were associated with language and memory impairment. Our study
      recommends that the neurocognitive impairment should be included in the DSM-V
      diagnostic criteria for schizophrenia.

PMID- 24459375
TI  - An analysis of paramilitary referrals to psychiatric services at a tertiary care
      center.
AB  - BACKGROUND: There is a dearth of specialized mental health services for Indian
      paramilitary service personnel. Those requiring psychiatric evaluation are
      referred to government psychiatric services often with minimal information.
      Hence, major diagnostic and decision making relies on the psychiatrist's clinical
      evaluation and judgment. The aim of the present study was to quantitatively
      evaluate the paramilitary referrals to psychiatric services at a tertiary care
      referral center. MATERIALS AND METHODS: A retrospective chart analysis of all
      consecutive referrals by various Indian paramilitary services to a tertiary care
      hospital (2008-2010) was carried out. RESULTS: Among the sample of 18 referrals,
      all were males (mean age: 37 years +/- standard deviation (SD) =7.79). Various
      reasons for referral included: Evaluation of fitness for duty (83.3%), fitness to
      handle firearms (16.7%), and for disability certification (5.6%). There were no
      informants at all in 22.2%, and family members were available in only 11.1%.
      Hence, most referrals were admitted to the psychiatry ward for observation for
      various lengths of time. The mean duration of assessment (outpatient and
      inpatient) was 17.89 days (SD = 20.74) and final reported diagnoses were
      schizophrenia, depression, and bipolar disorder in 16.7, 11.1, and 11.1%,
      respectively. There was concurrent history of alcohol and nicotine dependence
      (40%). A large group (40%) was diagnosed not to suffer from a major mental
      illness, while a firm and final diagnosis could not be arrived at in 16.7%
      subjects. Only one subject was given the fitness to handle firearms, fitness for
      duty was refused in three (16.7%) subjects, and one subject was referred to
      neurology after being diagnosed as a case of seizure disorder. CONCLUSION: There
      is an urgent need for intensive training both to paramilitary physicians as well
      as to general hospital psychiatrists regarding proper assessment of paramilitary
      personnel, as there are frequent chances of the cases being undiagnosed or
      improperly diagnosed.

PMID- 24459376
TI  - Metabolic syndrome among substance dependent men: A study from north India.
AB  - BACKGROUND: Substance abuse, alcohol in particular, is associated with increased
      risk of diabetes and metabolic syndrome (MS). The relationship between the
      substance abuse and MS is complex and the literature is sparse. OBJECTIVES: The
      present research was aimed to study the prevalence and predictors of MS among
      outpatients with substance dependence. MATERIALS AND METHODS: Patients with
      substance dependence were recruited from a deaddiction center in North India, who
      attended outpatient clinic from 1(st) January, 2010-31(st) December, 2010. MS was
      assessed using International Diabetes Federation (IDF) criteria. RESULTS: Out of
      250 subjects, 34 (13.6%) of the subjects met the IDF criteria for MS and highest
      being in alcohol group (21.6%). The commonest abnormality was increased
      triglycerides (TG; 54%) and increased waist circumference (36.8%). Age, body
      weight, body mass index, and obesity were significant predictor of MS.
      CONCLUSION: MS was highest in subjects with alcohol dependence with the commonest
      abnormality of TG and blood pressure. Hence, routine screening is advisable in
      this population to address emerging MS.

PMID- 24459377
TI  - Current social functioning in adult-onset schizophrenia and its relation with
      positive symptoms.
AB  - BACKGROUND: In schizophrenia, relation exists between psychopathology and social
      functioning. AIM AND OBJECTIVES: Determining relationship of positive symptoms
      with current social functioning in adult-onset (>=19 years) schizophrenia.
      MATERIALS AND METHODS: Eighty schizophrenia patients [ICD-10-DCR], of both sexes
      (18-60 years), on follow-up for >=6 months, with no change of diagnosis and
      without co-morbidities, having onset of illness >=19 years of age, accompanied by
      informants having contact with the patient for a period of >12 months prior the
      first psychiatric contact or symptom onset were assessed with SCARF- Social
      Functioning Index and SAPS. RESULTS: Family role, occupational role, and other
      social role have negative correlation with all positive symptoms. CONCLUSION:
      Current social functioning has significant negative correlation with concurrent
      positive symptoms.

PMID- 24459378
TI  - Cycloserine induced mania.
AB  - We report a 21-year-old male who developed manic symptoms after addition of
      second line anti-tuberculosis treatment for his multidrug resistant tuberculosis.
      We identified cycloserine as offending drug; and discuss the management and
      possible neurobiological mechanisms as etiological explanation and implications
      of manic switch caused by cycloserine. 

PMID- 24459379
TI  - Psychiatric ethics in war and peace.
AB  - Practice of psychiatry is a complex activity because the psychiatrist generally
      practises his art in an emotionally charged environment with patients who may not
      be in a in a state of mind to exercise autonomy as a result of cognitive
      impairment and preoccupation with symptoms. No one principle of ethics will be
      suitable to guide right conduct in widely variable situations. Making ethical
      judgements in the military context can be difficult and may have potential for
      abuse as for an uniformed psychiatrist mission takes priority over man. However
      mission centered and medical text book centred ethics need not be
      compartamentalised. The present paper seeks to offer a brief overview of ethical
      principles and specific situations in which one may have to make ethical
      judgements. 

PMID- 24459380
TI  - How to stop tobacco use? Tobacco user's perspective.
AB  - OBJECTIVES: To explore the tobacco-dependent subject's perspectives of what
      measures are likely to work for tobacco cessation. MATERIALS AND METHODS:
      Nicotine-dependent male subjects attending a tertiary level de-addiction center
      in North India were recruited. Demographic and clinical data was recorded. Open
      ended questions were asked to know user's perspective about the measures by which
      tobacco use can be effectively stopped in the country. The subjects were allowed
      as many responses as they desired. RESULTS: A total of 46 subjects were
      recruited. The median age of the sample was 35 years, with median duration of
      tobacco use being 12 years. All subjects were males, and most were married,
      employed, and had urban residence. Supply reducing measures were the most
      commonly reported to stop tobacco (67.4% of subjects) followed by people quitting
      tobacco use by themselves (19.6%) and raising awareness through media (13.1%).
      CONCLUSION: This pilot study reflects the perspectives of tobacco users for the
      measures likely to be effective in tobacco cessation. Evaluating the effect of
      implementation of individual policies may help focusing towards measures that
      yield greatest benefits.

PMID- 24459381
TI  - Hindi translation and validation of dysfunctional beliefs and attitudes about
      sleep (DBAS - 16).
AB  - OBJECTIVES: The objective of this study is to translate and validate the
      Dysfunctional Beliefs and Attitudes about Sleep Brief Version (DBAS-16)) in Hindi
      language. MATERIALS AND METHODS: The scale was obtained online, and the
      permission for translation was obtained from the author. The translation of the
      scale was carried out following back translation method. The scale was applied on
      63 participants attending the adult psychiatry OPD who were included in the
      study. RESULTS: Thirty-two patients were having insomnia, and 31 patients were
      controls without insomnia. The results show that the translated version had good
      reliability with internal consistency (Chronbach alpha = 0.901). CONCLUSION: The
      Hindi translation of DBAS-16 is a reliable tool for assessing the dysfunctional
      beliefs and attitude about sleep.

PMID- 24459382
TI  - Psychiatric morbidity at secondary level health facility in Ballabgarh, Haryana.
AB  - BACKGROUND: There is dearth of information about psychiatric morbidity at
      secondary level health facility in India. AIM: To study psychiatric morbidity
      amongst patients attending psychiatry clinic in secondary level health facility.
      SETTINGS AND DESIGN: Present study is based on hospital record review of
      psychiatry clinic at secondary care hospital in Ballabgarh, Haryana. MATERIALS
      AND METHODS: Service record of psychiatry clinic at civil hospital Ballabgarh was
      reviewed. Diagnosis of psychiatric morbidity was done according to DSM IV and ICD
      10 classification. STATISTICAL ANALYSIS: Descriptive analysis of data was carried
      out. RESULTS: A total of 724 (0.7%) new OPD patients consulted psychiatry clinic.
      Common Mental Disorders comprising of mood disorders, neurotic stress -related
      and somatoform disorders were the most commonly diagnosed disorders (60.5%)
      amongst reported psychiatric morbidity in the hospital. CONCLUSION: Substantial
      burden of psychiatry morbidity highlights necessity of psychiatry clinic at
      secondary care hospital in India.

PMID- 24459383
TI  - Historical future of Ayurveda.

PMID- 24459384
TI  - Seasonal variations in physicochemical profiles of Guduchi Satva (starchy
      substance from Tinospora cordifolia [Willd.] Miers).
AB  - Guduchi Satva (GS), the starchy material extracted from the Guduchi stem is well
      known Ayurvedic single drug formulation having a wide range of therapeutic
      utility. Species of the plant, stem size, collection time, season and maturity of
      the plant may affect the yield and physico-chemical profile of GS. However,
      published data on such variations is lacking. Considering this, present study is
      planned to screen seasonal variations in physico-chemical profile of GS. 18
      batches of GS were prepared in six different seasons (3 batches in each season)
      and findings were systematically recorded. The obtained Satva was further
      subjected to relevant physico-chemical parameters. Principal component analysis
      method was adopted to analyze variations. Maximum yield of Satva was obtained in
      Shishira Ritu(January-February) while the minimum in Grishma (May-June).
      Variation in taste and color was found in Satva prepared in Varsha Ritu. All
      functional groups were found to be same in each season. Total alkaloidal contents
      found bit higher in Varsha and Vasanta. More residual x-variance in alcohol
      soluble extract and more leverage were observed in water soluble extract due to
      impact of seasonal spells. 

PMID- 24459385
TI  - Foundational principles of classical Ayurveda research.
AB  - Double-blind randomized controlled trials (RCTs) are viewed as the golden
      standard of drug research in Western medicine. However, RCTs are far from
      "golden" in many respects. They are impractical for many therapies, such as for
      surgeries and complex lifestyle changes. They encourage a one-size-fits-all
      approach to medical treatment that fails to address the huge diversity among
      individual patients in terms of their physical and emotional symptoms, social and
      cultural upbringing, and other factors. Perhaps, more importantly, they do not
      help doctors make the best medical decisions required to produce optimal patient
      outcomes. To guide a search for an alternate model of medical research, three
      principles based on Ayurveda, an ancient and powerful system of health care that
      has stood the test of time, are presented. These principles, arrived at after
      mining Ayurvedic epistemology, are: Inductive learning, whole systems thinking,
      and individually optimized therapy. In honor of the ancient sages or "Rishis,"
      whose voice is used to deliver Ayurvedic knowledge in the ancient texts of
      Ayurveda, these are referred to as the "Rishi principles." Common research
      methodologies are examined for embodiment of these principles. 

PMID- 24459386
TI  - Experimental evaluation of horse hair as a nonabsorbable monofilament suture.
AB  - BACKGROUND: Success of surgery depends on wound closure and healing. Ancients had
      coated many suture materials from plant and animal origin. As the quest for
      natural nonabsorbable, monofilament surgical suture continues, horsehair has been
      taken for study, which is mentioned in ancient literature. OBJECTIVES: Aim of the
      study was to evaluate detail mechanical and biophysical properties of horsehair.
      MATERIALS AND METHODS: Physical properties, that are diameter, straight pull and
      knot pull tensile strength, bioburden, sterility tests were performed. Visual and
      histological wound healing parameters were studied in experimental Wistar rat
      incision wound model. Two experimental wounds about 5 cm long were created on
      each side of dorsal midline. Each animal received two sutures-Horsehair 4-0 and
      Ethilon 4-0. The sutured areas were grossly examined on 3(rd) and 7(th) days for
      visual observations like congestion, edema, infection, wound disruption, and
      impression of suture material on healed wound and then subjected for histological
      study. RESULTS: Revealed that horsehair has got diameter of 0.19 mm which
      complies with the 4-0 size USP standard. Straight pull tensile strength was found
      0.5851 +/- 0.122 kg and knot pull tensile strength was 0.3998 +/- 0.078 kg, which
      complies with the standards of United State Pharmacopia for class II
      nonabsorbable suture materials. In vivo study revealed that there was no evidence
      of edema, congestion, and discharge in both the groups. Wounds healed with
      minimum impressions of suture material with minimum scar mark. Mean histological
      scoring shows very mild tissue reaction. CONCLUSION: Horsehair has got properties
      of standard suture material except low tensile strength and hence can be used in
      reconstructive, plastic surgeries, and ophthalmic surgeries.

PMID- 24459387
TI  - Phytochemistry and hepatoprotective activity of aqueous extract of Amaranthus
      tricolor Linn. roots.
AB  - BACKGROUND: The genus Amaranthus has potential activity as a hepatoprotective
      agent. OBJECTIVE: The present pharmacological investigation focuses on evaluation
      of the efficacy of aqueous extract of roots of Amaranthus tricolor Linn. for
      their protection against paracetamol (PCM) overdose induced hepatotoxicity.
      MATERIALS AND METHODS: The aqueous extract of roots of A. tricolor Linn. was
      prepared and phytochemical screening was done. The biochemical investigation viz.
      serum glutamic oxaloacetate transaminase (SGOT), serum glutamic pyruvate
      transaminase (SGPT), alkaline phosphatase (ALP) and total Bilirubin (TB) was done
      against PCM-induced hepatotoxicity in wistar albino rats. The histopathological
      studies of liver were also done. RESULTS: The phytochemical screening of the
      aqueous extract showed the presence of alkaloids, carbohydrates, flavanoids,
      amino acids, proteins, fixed oil, saponins and tannins, and phenolic compounds.
      Pretreatment with the aqueous extract of root significantly prevented the
      physical, biochemical, histological, and functional changes induced by
      paracetamol in the liver. The extract showed significant hepatoprotective effects
      as evidenced by decreased serum enzyme activities like SGPT, SGOT, ALP, and TB,
      which was supported by histopathological studies of liver. The aqueous extract
      showed significant hepatoprotective activity comparable with standard drug
      silymarin as well as hepatotoxin drug PCM. CONCLUSION: From these results, it is
      concluded that the A. tricolor has potential effectiveness in treating liver
      damage in a dose dependent manner.

PMID- 24459388
TI  - Protective effect of nutmeg aqueous extract against experimentally-induced
      hepatotoxicity and oxidative stress in rats.
AB  - BACKGROUND: Nutmeg a well-known spice used as a folk medicine in India to treat
      stomach ailments. Worldwide it is commonly used for food preservation and
      fragrance. Abundant references were given for nutmeg in ayurveda, unani, and
      siddha as a single drug or as an important constituent in formulations.
      OBJECTIVE: In the present study, nutmeg aqueous extract (NMAET) was evaluated
      against isoproterenol (ISO)-induced hepatotoxicity and oxidative stress.
      MATERIALS AND METHODS: Antioxidant enzymes, liver functions tests, and lipid
      profile tests were performed using standard procedures. Histological examination
      of liver was done by fixing in formaldehyde solution and hematoxylin staining.
      RESULTS: Oral administration of NMAET effectively inhibited the ISO-induced
      changes in the activities of hepatic marker and antioxidant enzymes in plasma and
      heart tissue along with lipid peroxidation levels. The liver sections of ISO
      administered rats showed massive fatty changes, necrosis, ballooning
      degeneration, and broad infiltration of the lymphocytes and the loss of cellular
      boundaries; these changes were completely absent in groups treated with extract.
      Analysis of variance and Duncan's Multiple Range tests were used to perform
      statistical analysis. CONCLUSION: Results suggest that the NMAET possess
      significant potential as hepatoprotective and antioxidative agent against ISO
      induced damage in rats.

PMID- 24459389
TI  - Protective effect of Lannea coromandelica Houtt. Merrill. against three common
      pathogens.
AB  - BACKGROUND: Ayurvedic text reports suggested Lannea coromandelica is used in
      various microbial origin disorders like dysentery, sore eyes and leprosy, genital
      wounds. OBJECTIVE: The present study was designed to investigate the
      antimicrobial effect of L. coromandelica Houtt. Merrill. (Anacardiaceae) on
      microbes which cause female reproductive tract infection. MATERIALS AND METHODS:
      Ethanolic and aqueous bark extract (Ext.) of L. coromandelica were screened
      against strains of Streptococcus pyogens, Staphylococcus aureus, and Candida
      albicans. Antimicrobial assay had been done with agar well diffusion method.
      RESULTS: Ethanolic extracts [100% (16 mg), 75% (12 mg) and 50% (8 mg)] of L.
      coromandelica exhibited zone of inhibition (ZI) 19.21 mm, 18.45 mm, 16.41 mm and
      18.12 mm, 17.35 mm, 16.35 mm against S. aureus and S. pyogens, respectively.
      However, only 100% and 75% ethanolic extract showed (ZI-19.18 mm, 16.29 mm)
      activity against C. albicans. Nevertheless, aqueous extract (100%) showed higher
      antifungal activity (ZI-16.97 mm). Ciprofloxacin and amphotericin B were used as
      a standard drugs in the present study. CONCLUSION: The results demonstrated that
      L. coromandelica Houtt. Merrill. have antibacterial activity against S. pyogens,
      S. aureus and antifungal property against C. albicans. Our findings corroborate
      the ethnobotanical use of L. coromandelica in traditional medicine system
      (Ayurveda) of India.

PMID- 24459390
TI  - Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis:
      Six months open label randomized controlled clinical trial.
AB  - BACKGROUND: AmrutBhallatak (ABFN02), a 'rasayana' drug from Ayurveda is indicated
      in degenerative diseases and arthritis. OBJECTIVE: To evaluate safety and
      efficacy of ABFN02 in osteoarthritis (OA) and compare it with Glucosamine
      sulphate (GS). MATERIALS AND METHODS: This was a randomized open comparative
      study. Ambulant OPD patients of OA knees (n = 112) were enrolled for 24 weeks.
      Tablets (750mg each) of GS and ABFN02 were matched. Three groups of patients: (A)
      GS, one tablet * twice/day * 24 weeks. (B) ABFN02, incremental pulse dosage (one
      tablet x twice/day * two weeks, two tablets * twice/day * two weeks, three
      tablets * twice/day * two weeks), two such cycles of drug and non-drug phases
      alternately for six weeks each (C) ABFN02 continuous dosage akin to GS. Pain
      visual analogue score (Pain-VAS) and Western Ontario and Mc-Master University
      Osteoarthritis Index (WOMAC) were the primary outcome measures. Secondary outcome
      measures were Health assessment questionnaire (HAQ), paracetamol consumption, 50
      feet walking, physician and patient global assessment, knee stiffness, knee
      status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected
      patients. RESULTS: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and
      74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on
      activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively.
      Secondary outcome measures were comparable in all groups. Safety measures were
      also comparable. No serious adverse events reported. However, asymptomatic
      reversible rise in liver enzymes was noted in the ABFNO2 group. CONCLUSIONS:
      ABFN02 has significant activity in OA; the formulation needs further
      investigation.

PMID- 24459391
TI  - A holistic approach to the management of Erb's palsy.
AB  - A 4.5-month-old female baby, presenting with complete paralysis of right upper
      limb with typical waiter's tip deformity, diagnosed as Erb's palsy was brought to
      Sri Ganapati Sachchidananda Hospital. Patient was treated with an integrated
      approach of physiotherapy and Ayurvedic treatment with an intention of aiding
      faster recovery of the patient to lead a near normal life. As per Ayurvedic
      classics, this condition can be correlated to Ekangavata (Vata effecting any one
      part of the body), which is Apatarpana in nature (diseases with deprived growth
      of body tissue). Hence, the choice of treatment is Santarpana Chikitsa
      (nourishing treatment). Santarpana Bahyopakramas (nourishing external treatment
      modalities) such as Ashwagandhabalalakshadi Taila (Ayurvedic medicated oil)
      Abhyanga (oleation therapy) and Shastikashali Anna Lepa (application of processed
      rice paste) were administered along with electrical stimulation (physiotherapy
      modality), both galvanic and faradic current in three sessions. Appreciable
      results were observed in the form of reduction of disparity in length and mid-arm
      circumference of right upper limb compared to unaffected left upper limb and the
      muscle power too improved from zero to four, facilitating patient to near normal
      movement. 

PMID- 24459392
TI  - Kshara application for turbinate hypertrophy.
AB  - Nasapratinaha (nasal obstruction) is a commonly encountered disease in clinical
      practice. It is one of the nasal disorders, explained in Ayurveda, having nasal
      obstruction leading to difficulty in breathing as the main cardinal feature. In
      contemporary science, this condition can be correlated with various diseases such
      as turbinate hypertrophy, deviated nasal septum, nasal mass, mucosal congestion,
      allergic rhinitis, and others; among which turbinate hypertrophy is a common
      cause. Turbinate hypertrophy can be treated with surgical and medical methods.
      The medical treatment has limitation for prolonged use because of health purpose,
      surgical approaches too have failed to achieve desired results in turbinate
      hypertrophy due to complications and high recurrence rate. The medical and
      surgical managements have their own limitations, merits, and demerits like
      synechiae formation, rhinitis sicca, severe bleeding, or osteonecrosis of the
      turbinate bone A parasurgical treatment explained in Ayurveda, known as kshara
      pratisarana, which is a minimal invasive and precise procedure for this ailment,
      tried to overcome this problem. 'Kshara Karma' is a popular treatment modality in
      Ayurveda, which has been advocated in disorders of nose like arbuda (tumor) and
      adhimamsa (muscular growth). Clinical observation has shown its effectiveness in
      the management of turbinate hypertrophy. A case report of 45-year-old male who
      presented with complaints of frequent nasal obstruction, nasal discharge,
      discomfort in nose, and headache; and diagnosed as turbinate hypertrophy has been
      presented here. The patient was treated with one application of Kshara over the
      turbinates. The treatment was effective and no recurrence was noticed in the
      follow up. 

PMID- 24459393
TI  - Draft amendment to drugs and cosmetics rules to license science based botanicals,
      phytopharmaceuticals as drugs in India.

PMID- 24459394
TI  - Conference report - samyukti 2013.

PMID- 24459395
TI  - Samanvaya: conference on alternative medicine.

PMID- 24459396
TI  - Veterinary drug delivery.

PMID- 24459397
TI  - Use of rodents as models of human diseases.
AB  - Advances in molecular biology have significantly increased the understanding of
      the biology of different diseases. However, these discoveries have not yet been
      fully translated into improved treatments for patients with diseases such as
      cancers. One of the factors limiting the translation of knowledge from
      preclinical studies to the clinic has been the limitations of in vivo diseases
      models. In this brief review, we will discuss the advantages and disadvantages of
      rodent models that have been developed to simulate human pathologies, focusing in
      models that employ xenografts and genetic modification. Within the framework of
      genetically engineered mouse (GEM) models, we will review some of the current
      genetic strategies for modeling diseases in the mouse and the preclinical studies
      that have already been undertaken. We will also discuss how recent improvements
      in imaging technologies may increase the information derived from using these
      GEMs during early assessments of potential therapeutic pathways. Furthermore, it
      is interesting to note that one of the values of using a mouse model is the very
      rapid turnover rate of the animal, going through the process of birth to death in
      a very short timeframe relative to that of larger mammalian species. 

PMID- 24459398
TI  - Farmed deer: A veterinary model for chronic mycobacterial diseases that is
      accessible, appropriate and cost-effective.
AB  - Although most studies in immunology have used inbred mice as the experimental
      model to study fundamental immune mechanisms they have been proven to be limited
      in their ability to chart complex functional immune pathways, such as are seen in
      outbred populations of humans or animals. Translation of the findings from inbred
      mouse studies into practical solutions in therapeutics or the clinic has been
      remarkably unproductive compared with many other areas of clinical practice in
      human and veterinary medicine. Access to an unlimited array of mouse strains and
      an increasing number of genetically modified strains continues to sustain their
      paramount position in immunology research. Since the mouse studies have provided
      little more than the dictionary and glossary of immunology, another approach will
      be required to write the classic exposition of functional immunity. Domestic
      animals such as ruminants and swine present worthwhile alternatives as models for
      immunological research into infectious diseases, which may be more informative
      and cost effective. The original constraint on large animal research through a
      lack of reagents has been superseded by new molecular technologies and robotics
      that allow research to progress from gene discovery to systems biology,
      seamlessly. The current review attempts to highlight how exotic animals such as
      deer can leverage off the knowledge of ruminant genomics to provide cost
      effective models for research into complex, chronic infections. The unique
      opportunity they provide relates to their diversity and polymorphic genotypes and
      the integrity of their phenotype for a range of infectious diseases. 

PMID- 24459399
TI  - A cyclodextrin formulation to improve use of the anesthetic tribromoethanol
      (Avertin((r))).
AB  - OBJECTIVE: Efficacy and safety concerns have been raised in the literature with
      the use of tribromoethanol (TBE) (Avertin((r))) for anesthesia in rats and mice
      when administered by intraperitoneal (IP) injection. Despite the controversy, it
      remains in common usage as an anesthetic agent in laboratory rodents for short
      term surgical procedures. Cyclodextrins have been shown to improve drug
      solubility and were investigated here as an improved anesthetic formulation for
      mice. MATERIALS AND METHODS: The phase solubility of TBE with hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) was estimated. The efficacy of two anesthetic regimens
      was compared in this study; the conventional TBE formulation solubilized in tert
      amyl alcohol and a HP-beta-CD formulation containing TBE. Mice (n = 6) were
      administered the formulations by IP injection and the pharmacodynamic parameters
      of time to induction of anesthesia, duration of anesthesia and recovery time were
      measured using a combined reflex score (CRS). RESULTS AND DISCUSSION: Phase
      solubility studies showed a linear increase in the solubility of TBE with
      increasing HP-beta-CD concentration and suggested >1:1 binding of the drug in the
      cyclodextrin complex. At a dose of 260 mg/kg the standard TBE formulation
      appeared to produce deeper anesthesia than the cyclodextrin formulation, with a
      minimum average CRS of 1.8 compared with 5.2. No post-mortem pathology was
      observed in mice that received either the conventional or cyclodextrin
      formulation. CONCLUSION: The cyclodextrin TBE formulation did not conclusively
      provide an improved anesthetic response at a dose of 260 mg/kg compared with the
      conventional formulation. The improved solubility of TBE with HP-beta-CD and the
      reduced variability in anesthetic response warrants the further investigation of
      this formulation. This study has also identified the value of using the
      anticholinergic atropine in association with TBE for anesthesia.

PMID- 24459400
TI  - Buparvaquone loaded solid lipid nanoparticles for targeted delivery in
      theleriosis.
AB  - BACKGROUND: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been
      investigated for the treatment of many infections and is recommended as the gold
      standard for the treatment of theileriosis. Theileriosis, an intramacrophage
      infection is localized mainly in reticuloendotheileial system (RES) organs. The
      present study investigates development of solid lipid nanoparticles (SLN) of BPQ
      for targeted delivery to the RES. MATERIALS AND METHODS: BPQ SLN was prepared
      using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80
      degrees C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN
      of designed size were obtained using ultraturrax and high pressure homogenizer. A
      freeze and thaw study was used to optimize type and concentration of
      cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3.
      Differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and
      scanning electron microscope (SEM) study was performed on optimized formulation.
      Formulation was investigated for in vitro serum stability, hemolysis and cell
      uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman
      rat. RESULTS: Based on solubility in lipid; glyceryl monostearate (GMS) was
      selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for
      average particle size and entrapment efficiency at <100 mg solid content. A
      combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the
      desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray
      diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning
      electron microscope revealed spherical morphology. BPQ SLN revealed good
      stability at 4 degrees C and 25 degrees C. Low hemolytic potential (<8%) and in
      vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937
      cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1
      h suggesting the potential to RES uptake. SLN revealed longer circulation and
      biodistrbution study confirmed high RES uptake (75%) in RES organs like liver
      lung spleen etc. CONCLUSION: The high RES uptake suggests BPQ SLN as a promising
      approach for targeted and improved delivery in theileriosis.

PMID- 24459401
TI  - New oral anthelmintic intraruminal delivery device for cattle.
AB  - BACKGROUND: The purpose of this work was to develop a new oral drug delivery
      system intended for cattle and that enables delayed and pulsed release of an
      anthelmintic agent. MATERIALS: This new tailored dosage form, also called
      reticulo-rumen device (RRD) has been evaluated on grazing calves by means of
      measurements of milliunits of tyrosine concentration, number of eggs per gram of
      feces, mean number of infective larvae on cattle pasture and increase in mean
      weight of cattle. METHODS: The in vivo evaluation was carried out during two
      grazing seasons on different groups of dairy cattle. During the first grazing
      season, Group 1 was designated as an untreated control group. The remaining two
      were assigned to different treatments as follows: Group 2, early season
      suppression with a marketed intraruminal slow release bolus (Chronomintic((r)),
      Virbac) administered immediately prior to turn-out and Group 3, mid-season
      suppression with a new RRD administered immediately prior to turn out. When the
      cattle were turned out at the start of the second grazing season, they were not
      given any anthelmintic treatment and were divided into two different groups,
      corresponding to the previous groups that received an anthelmintic treatment
      during the first grazing season, on that pasture that they had occupied as
      separate groups in the previous year. Furthermore, during the second season,
      samples of feces, blood and herbage were collected every month. RESULTS AND
      CONCLUSION: During the first grazing season, the results indicated that the fecal
      egg counts and the number of infective larvae in herbage samples were slightly
      lower for the group receiving the new RRDs. Regular weighing of the cattle
      receiving the new RRDs revealed no significant difference with cattle receiving
      marketed RRDs. Conversely, during the second grazing season, the results for the
      mean weights of the cattle demonstrated that the weights of animals having been
      administered new RRDs during the first grazing season were significantly
      different (P < 0.05) from those in the second group treated with a
      Chronomintic((r)) during the first grazing season. A difference in mean weight of
      26 kg was observed between these two groups.

PMID- 24459402
TI  - Subcutaneous implants for long-acting drug therapy in laboratory animals may
      generate unintended drug reservoirs.
AB  - BACKGROUND: Long-acting therapy in laboratory animals offers advantages over the
      current practice of 2-3 daily drug injections. Yet little is known about the
      disintegration of biodegradable drug implants in rodents. OBJECTIVE: Compare
      bioavailability of buprenorphine with the biodegradation of lipid-encapsulated
      subcutaneous drug pellets. METHODS: Pharmacokinetic and histopathology studies
      were conducted in BALB/c female mice implanted with cholesterol-buprenorphine
      drug pellets. RESULTS: Drug levels are below the level of detection (0.5 ng/mL
      plasma) within 4-5 days of implant. However, necroscopy revealed that
      interstitial tissues begin to seal implants within a week. Visual inspection of
      the implant site revealed no evidence of inflammation or edema associated with
      the cholesterol-drug residue. Chemical analyses demonstrated that the residues
      contained 10-13% of the initial opiate dose for at least two weeks post implant.
      DISCUSSION: The results demonstrate that biodegradable scaffolds can become
      sequestered in the subcutaneous space. CONCLUSION: Drug implants can retain
      significant and unintended reservoirs of drugs.

PMID- 24459403
TI  - Thermal latency studies in opiate-treated mice.
AB  - BACKGROUND: The change in the reaction time of a tail or paw exposed to a thermal
      stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick
      and plantar thermal sensitivity (Hargreaves) tests are non-invasive, minimize
      stress, and can be used to screen animals for phenotype and drug activity.
      OBJECTIVE: Hargreaves testing has been widely used in rats. We investigated its
      use to measure the activity of opiate analgesia in mice. METHODS: Mice were used
      in thermal stimulus studies at 1-5 hours and 1-5 days to test acute and extended
      release preparations of buprenorphine. RESULTS: Hargreaves testing had limited
      value at 1-5 hours because mice can have an obtunded response to opiate therapy.
      Tail-flick studies with restrained mice are not affected by the initial locomotor
      stimulation. DISCUSSION: The present report describes a simple restraint system
      for mice. The utility of the system is demonstrated by examining the efficacy of
      acute and extended release buprenorphine injections in Balb/c and Swiss mice.
      CONCLUSION: Standardized tail-flick testing provides a sensitive robust method to
      monitor opiate activity in mice.

PMID- 24459404
TI  - Neuroprotective and nootropic activity of Clitorea ternatea Linn.(Fabaceae)
      leaves on diabetes induced cognitive decline in experimental animals.
AB  - PURPOSE: Ethanol extract of Clitorea ternatea (EECT) was evaluated in diabetes
      induced cognitive decline rat model for its nootropic and neuroprotective
      activity. MATERIALS AND METHODS: Effect on spatial working memory, spatial
      reference memory and spatial working-reference memory was evaluated by Y maze,
      Morris water maze and Radial arm maze respectively. Neuroprotective effects of
      EECT was studied by assaying acetylcholinesterase, lipid peroxide, superoxide
      dismutase (SOD), total nitric oxide (NO), catalase (CAT) and glutathione (GSH)
      levels in the brain of diabetic rats. RESULTS: The EECT (200 and 400 mg/kg) was
      found to cause significant increase in spatial working memory (P < 0.05), spatial
      reference memory (P < 0.001) and spatial working-reference (P < 0.001) in
      retention trials on Y maze, Morris water maze and Radial arm maze respectively.
      Whereas significant decrease in acetylcholinesterase activity (P < 0.05), lipid
      peroxide (P < 0.001), total NO (P < 0.001) and significant increase in SOD, CAT
      and GSH levels was observed in animals treated with EECT (200 and 400 mg/kg)
      compared to diabetic control group. CONCLUSIONS: The present data indicates that
      Clitorea ternatea tenders protection against diabetes induced cognitive decline
      and merits the need for further studies to elucidate its mode of action.

PMID- 24459405
TI  - Optimal treatment of actinic keratosis.

PMID- 24459406
TI  - Memory: from the laboratory to everyday life.
AB  - One of the key goals of memory research is to develop a basic understanding of
      the nature and characteristics of memory processes and systems. Another important
      goal is to develop useful applications of basic research to everyday life. This
      editorial considers two lines of work that illustrate some of the prospects for
      applying memory research to everyday life: interpolated quizzing to enhance
      learning in educational settings, and specificity training to enhance memory and
      associated functions in individuals who have difficulties remembering details of
      their past experiences. 

PMID- 24459407
TI  - Memory in health and in schizophrenia.
AB  - Memory is an important capacity needed for survival in a changing environment,
      and its principles are shared across species. These principles have been studied
      since the inception of behavioral science, and more recently neuroscience has
      helped understand brain systems and mechanisms responsible for enabling aspects
      of memory. Here we outline the history of work on memory and its neural
      underpinning, and describe the major dimensions of memory processing that have
      been evaluated by cognitive neuroscience, focusing on episodic memory. We present
      evidence in healthy populations for sex differences-females outperforming in
      verbal and face memory, and age effects-slowed memory processes with age. We then
      describe deficits associated with schizophrenia. Impairment in schizophrenia is
      more severe in patients with negative symptoms-especially flat affect-who also
      show deficits in measures of social cognition. This evidence implicates medial
      temporal and frontal regions in schizophrenia. 

PMID- 24459408
TI  - The "working" of working memory.
AB  - This review examines the evidence for a neurobiological explanation of executive
      functions of working memory. We suggest that executive control stems from
      information about task rules acquired by mixed selective, adaptive coding,
      multifunctional neurons in the prefrontal cortex. The output of these neurons
      dynamically links the cortex-wide networks needed to complete the task. The
      linking may occur via synchronizing of neural rhythms, which may explain why we
      have a limited capacity for simultaneous thought. 

PMID- 24459409
TI  - A neurobiological approach to the cognitive deficits of psychiatric disorders.
AB  - Deficits in brain networks that support cognitive regulatory functions are
      prevalent in many psychiatric disorders. Findings across neuropsychology and
      neuroimaging point to broad-based impairments that cross traditional diagnostic
      boundaries. These dysfunctions are largely separate from the classical symptoms
      of the disorders, and manifest in regulatory problems in both traditional
      cognitive and emotional domains. As such, they relate to the capacity of patients
      to engage effectively in their daily lives and activity, often persist even in
      the face of symptomatically effective treatment, and are poorly targeted by
      current treatments. Advances in cognitive neuroscience now allow us to ground an
      understanding of these cognitive regulatory deficits in the function and
      interaction of key brain networks. This emerging neurobiological understanding
      furthermore points to several promising routes for novel neuroscience-informed
      treatments targeted more specifically at improving cognitive function in a range
      of psychiatric disorders. 

PMID- 24459410
TI  - Cellular basis of memory for addiction.
AB  - DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG
      ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a
      drug of abuse to induce changes in a vulnerable brain that drive the compulsive
      seeking and taking of drugs, and loss of control over drug use, that define a
      state of addiction. Here, we review the types of molecular and cellular
      adaptations that occur in specific brain regions to mediate addiction-associated
      behavioral abnormalities. These include alterations in gene expression achieved
      in part via epigenetic mechanisms, plasticity in the neurophysiological
      functioning of neurons and synapses, and associated plasticity in neuronal and
      synaptic morphology mediated in part by altered neurotrophic factor signaling.
      Each of these types of drug-induced modifications can be viewed as a form of
      "cellular or molecular memory." Moreover, it is striking that most addiction
      related forms of plasticity are very similar to the types of plasticity that have
      been associated with more classic forms of "behavioral memory," perhaps
      reflecting the finite repertoire of adaptive mechanisms available to neurons when
      faced with environmental challenges. Finally, addiction-related molecular and
      cellular adaptations involve most of the same brain regions that mediate more
      classic forms of memory, consistent with the view that abnormal memories are
      important drivers of addiction syndromes. The goal of these studies which aim to
      explicate the molecular and cellular basis of drug addiction is to eventually
      develop biologically based diagnostic tests, as well as more effective treatments
      for addiction disorders. 

PMID- 24459411
TI  - Memory loss in Alzheimer's disease.
AB  - Loss of memory is among the first symptoms reported by patients suffering from
      Alzheimer's disease (AD) and by their caretakers. Working memory and long-term
      declarative memory are affected early during the course of the disease. The
      individual pattern of impaired memory functions correlates with parameters of
      structural or functional brain integrity. AD pathology interferes with the
      formation of memories from the molecular level to the framework of neural
      networks. The investigation of AD memory loss helps to identify the involved
      neural structures, such as the default mode network, the influence of epigenetic
      and genetic factors, such as ApoE4 status, and evolutionary aspects of human
      cognition. Clinically, the analysis of memory assists the definition of AD
      subtypes, disease grading, and prognostic predictions. Despite new AD criteria
      that allow the earlier diagnosis of the disease by inclusion of biomarkers
      derived from cerebrospinal fluid or hippocampal volume analysis,
      neuropsychological testing remains at the core of AD diagnosis. 

PMID- 24459412
TI  - Disorders of memory and plasticity in psychiatric disease.
AB  - Plasticity is found throughout the nervous system and is thought to underlie key
      aspects of development, learning and memory, and repair. Neuropiastic processes
      include synaptic plasticity, cellular growth and remodeling, and neurogenesis.
      Dysregulation of these processes can contribute to a variety of neuropsychiatric
      diseases. In this review we explore three different ways in which dysregulation
      of neuropiastic and mnemonic processes can contribute to psychiatric illness.
      First, impairment of the mechanisms of plasticity can lead to cognitive deficits;
      this is most obvious in dementia and amnesia, but is also seen in more subtle
      forms in other conditions. We explore the relationship between stress, major
      depression, and impaired neuroplasticity in some detail. Second, enhanced
      memories can be pathogenic; we explore the example of post-traumatic stress
      disorder, in which intrusive trauma associated memories, accompanied by
      hyperactivity of the normal fear learning circuitry, are core aspects of the
      pathology. Third, impaired modulation of the relationship between parallel memory
      systems can contribute to maladaptive patterns of behavior; we explore the bias
      towards inflexible, habit-like behavior patterns in drug addiction and obsessive
      compulsive disorder. Together, these examples illustrate how different
      abnormalities in the mechanisms of neuroplasticity and memory formation can
      contribute to various forms of psychopathology. It is hoped that a growing
      understanding of these relationships, and of the fundamental mechanisms
      underlying neuroplasticity in the normal brain, will pave the way for new
      understandings of the mechanisms of neuropsychiatric disease and the development
      of novel treatment strategies. 

PMID- 24459413
TI  - Non-Alzheimer's disease-related memory impairment and dementia.
AB  - Although Alzheimer's disease (AD) is a common cause of memory impairment and
      dementia in the elderly disturbed memory function is a widespread subjective
      and/or objective symptom in a variety of medical conditions. The early detection
      and correct distinction of AD from non-AD memory impairment is critically
      important to detect possibly treatable and reversible underlying causes. In the
      context of clinical research, it is crucial to correctly distinguish between AD
      or non-AD memory impairment in order to build homogenous study populations for
      the assessment of new therapeutic possibilities. The distinction of AD from non
      AD memory impairment may be difficult, especially in mildly affected patients,
      due to an overlap of clinical symptoms and biomarker alterations between AD and
      certain non-AD conditions. This review aims to describe recent aspects of the
      differential diagnosis of AD and non-AD related memory impairment and how these
      may be considered in the presence of memory deficits. 

PMID- 24459415
TI  - Imaging autobiographical memory.
AB  - Autobiographical memory (AM) defines the memory systems that encode, consolidate,
      and retrieve personal events and facts, AM is strongly related to self-perception
      and self representation. We review here the neural correlates of AM retrieval. AM
      retrieval encompasses a large neural network including the prefrontal, temporal,
      and parietal cortex, and limbic structures. All these regions subserve the
      cognitive processes (episodic remembering, cognitive control, self-processing,
      and scene construction) at play during memory retrieval. We emphasize the
      specific role of medial prefrontal cortex and precuneus in self-processing during
      autobiographical memory retrieval. Overall, these data call for further studies
      in psychiatric patients, to investigate the neural underpinnings of
      autobiographical memory and self-representation in mental disorders. 

PMID- 24459414
TI  - Memory as a new therapeutic target.
AB  - This review aims to demonstrate how an understanding of the brain mechanisms
      involved in memory provides a basis for; (i) reconceptualizing some mental
      disorders; (ii) refining existing therapeutic tools; and (iii) designing new ones
      for targeting processes that maintain these disorders. First, some of the stages
      which a memory undergoes are defined, and the clinical relevance of an
      understanding of memory processing by the brain is discussed. This is followed by
      a brief review of some of the clinical studies that have targeted memory
      processes. Finally, some new insights provided by the field of neuroscience with
      implications for conceptualizing mental disorders are presented. 

PMID- 24459417
TI  - Solid phase extraction of inorganic mercury using 5-phenylazo-8-hydroxyquinoline
      and determination by cold vapor atomic fluorescence spectroscopy in natural water
      samples.
AB  - 8-Hydroxyquinoline (8-HQ) was chosen as a powerful ligand for Hg solid phase
      extraction. Among several chelating resins based on 8-HQ, 5-phenylazo-8
      hydroxyquinoline (5Ph8HQ) is used for mercury extraction in which the adsorption
      dynamics were fully studied. It has been shown that Hg(II) is totally absorbed by
      5Ph8HQ within the first 30 minutes of contact time with t 1/2 5 minutes,
      following Langmuir adsorption model. At pH 4, the affinity of mercury is
      unchallenged by other metals except, for Cu(II), which have shown higher Kd
      value. With these latter characteristics, 5Ph8HQ was examined for the
      preconcentration of trace levels of Hg(II). The developed method showed
      quantitative recoveries of Hg(II) with LOD = 0.21 pg mL(-1) and RSD = 3-6% using
      cold vapor atomic fluorescence spectroscopy (CV-AFS) with a preconcentration
      factor greater than 250.

PMID- 24459418
TI  - Effects of the tip location on single piles subjected to surcharge and axial
      loads.
AB  - When applying axial load on piles subjected to negative skin friction (NSF), the
      yielded NSF is gradually eliminated. The process is notably influenced by the tip
      location (Y) and still a lack of understanding. This paper reports three
      dimensional numerical simulations with tip locations Y = 1.00 pile diameter (D),
      0.25D, 0.00D, and -1.00D. It is found that, against expectations, the dragload
      and NSF are not proportionally related to the tip location. When maximum dragload
      (P max) is eventually eliminated due to an axial load, there is also a negative
      crest of the skin friction, indicating that NSF still exists based on the
      criterion of the dragload reduction. The side resistance of the piles with Y =
      1.00D and 0.25D is almost fully mobilised, which is demonstrated by the increment
      of end resistance that greatly increases with the larger axial loads. However,
      the side resistance of the piles with Y = 0.00D and -1.00D has a potential
      capacity to carry more loads with continued displacement since the increment of
      end resistance increases almost linearly with axial load. Therefore, when
      designing the pile foundation, the inclusion of the NSF should be governed by the
      amount of axial load to be resisted.

PMID- 24459419
TI  - Structure-activity relationships of 3,3'-phenylmethylene-bis-4-hydroxycoumarins:
      selective and potent inhibitors of gram-positive bacteria.
AB  - Dicoumarols and coumarin derivatives have shown a variety of pharmaceutical
      activities and have been found to be potent inhibitor for the NAD(P)H-dependent
      flavoproteins. In this report, dicoumarol and its derivatives containing the
      substituted benzene ring at the methylenebis position were synthesized and
      evaluated for their antibacterial activity against gram-positive bacteria:
      Staphylococcus aureus and Bacillus subtilis, and gram-negative bacteria:
      Escherichia coli and Klebsiella sp. The results showed that the synthesized
      dicoumarols affect cell growth but are selective against gram-positive over gram
      negative bacterial cells. However, for most derivatives, the substitution of
      steric bulky benzene group on the methylenebis position appears to decrease in
      the efficacy of antibacterial effect. This finding is roughly described by the
      predicted poorer docked structure of the derivatives to a homology model of S.
      aureus flavoprotein. 3D-QSAR study highlighted structural features around the
      substituted benzene ring of dicoumarols as the antibacterial activity. CoMFA and
      CoMSIA contour maps support the idea that steric repulsion at the para position
      could diminish the antibacterial activity. The results of this study provide a
      better understanding of the molecular basis for the antibacterial activity of
      dicoumarols. 

PMID- 24459420
TI  - Coexistence of 3G repeaters with LTE base stations.
AB  - Repeaters have been an attractive solution for mobile operators to upgrade their
      wireless networks at low cost and to extend network coverage effectively. Since
      the first LTE commercial deployment in 2009, many mobile operators have launched
      LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency
      bands are shared with the frequency bands for LTE deployment and 3G mobile
      operators have an enormous number of repeaters, reusing 3G repeaters in LTE
      networks is definitely a practical and cost-efficient solution. However, 3G
      repeaters usually do not support spatial multiplexing with multiple antennas, and
      thus it is difficult to reuse them directly in LTE networks. In order to support
      spatial multiplexing of LTE, the role of 3G repeaters should be replaced with
      small LTE base stations or MIMO-capable repeaters. In this paper, a repeater
      network is proposed to reuse 3G repeaters in LTE deployment while still
      supporting multilayer transmission of LTE. Interestingly, the proposed network
      has a higher cluster throughput than an LTE network with MIMO-capable repeaters. 

PMID- 24459421
TI  - Chlamydia pneumoniae antibodies and C-reactive protein levels in patients with
      abdominal aortic aneurysms.
AB  - INTRODUCTION: The study aim was to assess the relationship between the presence
      of antibodies to Chlamydia pneumoniae and abdominal aortic aneurysm (AAA)
      incidence. PATIENTS AND METHODS: Consecutive AAA patients and AAA-free controls
      were recruited prospectively. Serum samples from both groups were examined to
      determine Immunoglobulin (Ig) A and IgG titres against Chlamydia pneumoniae by
      ELISA and C-reactive protein (CRP) concentrations. Results were expressed as mean
      (SD) or median (IQR) and compared using chi (2) and Mann-Whitney U tests. A P
      value of <0.05 was considered statistically significant. RESULTS: Each study
      group (AAA/nAAA) comprised 250 patients. 196 (78.7%) AAA patients had positive
      IgA antichlamydial antibody titres, compared to 181 (72.4%) in the control group
      (P = 0.008, OR 2.0, 95% CI 1.2-3.5). However, positive IgG antibody titres were
      similar (191 versus 203; P = 0.222, OR 0.7, 95% CI 0.4-1.3). Average CRP
      concentrations were higher in AAA individuals. IgA or IgG antibody titres were
      not related to CRP concentrations. CONCLUSIONS: These results demonstrated that
      the frequent incidence of Chlamydia pneumoniae antibodies within the general
      population makes it difficult to relate its presence to AAA development, despite
      the high IgA antibody titres. In addition, raised CRP concentrations in AAA
      patients are not related to the presence of antichlamydial antibodies.

PMID- 24459422
TI  - Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing
      G2/M cell cycle arrest and promoting apoptosis.
AB  - AIMS: To further investigate the antineuroblastoma effect of rutin which is a
      type of flavonoid. METHODS: The antiproliferation of rutin in human neuroblastoma
      cells LAN-5 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Chemotaxis of LAN-5 cells was assessed using transwell
      migration chambers and scratch wound migration assay. The cell cycle arrest and
      apoptosis in a dose-dependent manner was measured by flow cytometric and
      fluorescent microscopy analyses. The apoptosis-related proteins BAX and BCL2 as
      well as MYCN mRNA express were determined by RT-PCR analysis. Secreted TNF- alpha
      level were determined using specific enzyme-linked immunosorbent assay kits.
      RESULTS: Rutin significantly inhibited the growth of LAN-5 cells and chemotactic
      ability. Flow cytometric analysis revealed that rutin induced G2/M arrest in the
      cell cycle progression and induced cell apoptosis. The RT-PCR showed that rutin
      could decrease BCL2 expression and BCL2/BAX ratio. In the meantime, the MYCN mRNA
      level and the secretion of TNF- alpha were inhibited. CONCLUSION: These results
      suggest that rutin produces obvious antineuroblastoma effects via induced G2/M
      arrest in the cell cycle progression and induced cell apoptosis as well as
      regulating the expression of gene related to apoptosis and so on. It supports the
      viability of developing rutin as a novel therapeutic prodrug for neuroblastoma
      treatment, as well as providing a new path on anticancer effect of Chinese
      traditional drug.

PMID- 24459424
TI  - Intercomparison of vertical structure of storms revealed by ground-based (NMQ)
      and spaceborne radars (CloudSat-CPR and TRMM-PR).
AB  - Spaceborne radars provide great opportunities to investigate the vertical
      structure of clouds and precipitation. Two typical spaceborne radars for such a
      study are the W-band Cloud Profiling Radar (CPR) and Ku-band Precipitation Radar
      (PR), which are onboard NASA's CloudSat and TRMM satellites, respectively.
      Compared to S-band ground-based radars, they have distinct scattering
      characteristics for different hydrometeors in clouds and precipitation. The
      combination of spaceborne and ground-based radar observations can help in the
      identification of hydrometeors and improve the radar-based quantitative
      precipitation estimation (QPE). This study analyzes the vertical structure of the
      18 January, 2009 storm using data from the CloudSat CPR, TRMM PR, and a NEXRAD
      based National Mosaic and Multisensor QPE (NMQ) system. Microphysics above,
      within, and below the melting layer are studied through an intercomparison of
      multifrequency measurements. Hydrometeors' type and their radar scattering
      characteristics are analyzed. Additionally, the study of the vertical profile of
      reflectivity (VPR) reveals the brightband properties in the cold-season
      precipitation and its effect on the radar-based QPE. In all, the joint analysis
      of spaceborne and ground-based radar data increases the understanding of the
      vertical structure of storm systems and provides a good insight into the
      microphysical modeling for weather forecasts. 

PMID- 24459423
TI  - Hydrogel-based nanocomposites and mesenchymal stem cells: a promising synergistic
      strategy for neurodegenerative disorders therapy.
AB  - Hydrogel-based materials are widely employed in the biomedical field. With regard
      to central nervous system (CNS) neurodegenerative disorders, the design of
      injectable nanocomposite hydrogels for in situ drug or cell release represents an
      interesting and minimally invasive solution that might play a key role in the
      development of successful treatments. In particular, biocompatible and
      biodegradable hydrogels can be designed as specific injectable tools and loaded
      with nanoparticles (NPs), to improve and to tailor their viscoelastic properties
      upon injection and release profile. An intriguing application is hydrogel loading
      with mesenchymal stem cells (MSCs) that are a very promising therapeutic tool for
      neurodegenerative or traumatic disorders of the CNS. This multidisciplinary
      review will focus on the basic concepts to design acellular and cell-loaded
      materials with specific and tunable rheological and functional properties. The
      use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic
      strategy for nervous tissue applications will be then discussed. 

PMID- 24459425
TI  - Electricity load forecasting using support vector regression with memetic
      algorithms.
AB  - Electricity load forecasting is an important issue that is widely explored and
      examined in power systems operation literature and commercial transactions in
      electricity markets literature as well. Among the existing forecasting models,
      support vector regression (SVR) has gained much attention. Considering the
      performance of SVR highly depends on its parameters; this study proposed a
      firefly algorithm (FA) based memetic algorithm (FA-MA) to appropriately determine
      the parameters of SVR forecasting model. In the proposed FA-MA algorithm, the FA
      algorithm is applied to explore the solution space, and the pattern search is
      used to conduct individual learning and thus enhance the exploitation of FA.
      Experimental results confirm that the proposed FA-MA based SVR model can not only
      yield more accurate forecasting results than the other four evolutionary
      algorithms based SVR models and three well-known forecasting models but also
      outperform the hybrid algorithms in the related existing literature. 

PMID- 24459426
TI  - Association of self-DNA mediated TLR9-related gene, DNA methyltransferase, and
      cytokeratin protein expression alterations in HT29-cells to DNA fragment length
      and methylation status.
AB  - To understand the biologic role of self-DNA bound to Toll-like Receptor 9 (TLR9),
      we assayed its effect on gene and methyltransferase expressions and cell
      differentiation in HT29 cells. HT29 cells were incubated separately with type-1
      (normally methylated/nonfragmented), type-2 (normally methylated/fragmented),
      type-3 (hypermethylated/nonfragmented), or type-4 (hypermethylated/fragmented)
      self-DNAs. Expression levels of TLR9-signaling and proinflammatory cytokine
      related genes were assayed by qRT-PCR. Methyltransferase activity and cell
      differentiation were examined by using DNA methyltransferase (DNMT1, -3A, -3B)
      and cytokeratin (CK) antibodies. Treatment with type-1 DNA resulted in
      significant increase in TLR9 expression. Type-2 treatment resulted in the
      overexpression of TLR9-related signaling molecules (MYD88A, TRAF6) and the IL8
      gene. In the case of type-3 treatment, significant overexpression of NFkB, IRAK2,
      and IL8 as well as downregulation of TRAF6 was detected. Using type-4 DNA, TRAF6
      and MYD88A gene expression was upregulated, while MYD88B, IRAK2, IL8, and TNFSF10
      were all underexpressed. CK expression was significantly higher only after type-1
      DNA treatment. DNMT3A expression could also be induced by type-1 DNA treatment.
      DNA structure may play a significant role in activation of the TLR9-dependent and
      even independent proinflammatory pathways. There may be a molecular link between
      TLR9 signaling and DNMT3A. The mode of self-DNA treatment may influence HT29 cell
      differentiation. 

PMID- 24459427
TI  - Twenty-four-hour urinary aldosterone predicts inappropriate left ventricular mass
      index in patients with primary aldosteronism.
AB  - OBJECTIVE: Primary aldosteronism (PA) is associated with inappropriate left
      ventricular hypertrophy (LVH) in relation to a given gender and body size. There
      is no ideal parameter to predict the presence of LVH or inappropriate LVH in
      patients with PA. We investigate the performance of 24-hour urinary aldosterone
      level, plasma renin activity and aldosterone-to-renin ratio on this task.
      METHODS: We performed echocardiography in 106 patients with PA and 31 subjects
      with essential hypertension (EH) in a tertiary teaching hospital. Plasma renin
      activity, aldosterone concentration, and 24-hour urinary aldosterone level were
      measured. RESULTS: Only 24-hour urinary aldosterone was correlated with left
      ventricular mass index (LVMI) and excess LVMI among these parameters. The
      multivariate analysis revealed the urinary aldosterone level as an independent
      predictor for LVMI and excess LVMI. Analyzing the ability of urinary aldosterone,
      plasma aldosterone concentration, and plasma aldosterone-to-renin ratio to
      identify the presence of LVH (ROC AUC = 0.701, 0.568, 0.656, resp.) and the
      presence of inappropriate LV mass index (defined as measured LVMI in predicting
      LVMI ratio >135%) (ROC area under curve = 0.61, 0.43, 0.493, resp.) revealed the
      better performance of 24-hour urinary aldosterone. CONCLUSIONS: In conclusion, 24
      hour urinary aldosterone level performed better to predict the presence of LVH
      and inappropriate LVMI in patients with PA.

PMID- 24459428
TI  - Biological and demographic profile of meningiomas in a cohort of Egyptian
      patients: impact on tumor recurrence.
AB  - OBJECTIVE: This work was designed to study the biological and demographic
      characteristics of meningiomas and their impact on tumor recurrence in Egyptian
      patients. MATERIAL AND METHODS: A cohort of 265 Egyptian patients with meningioma
      was studied. Immunohistochemistry for VEGF, Ki67, PR, CD20, and CD3 was
      performed. Statistical analysis was used to detect independent predictors of
      recurrence. RESULTS: Adults represented 98.9% of cases, with female preponderance
      (M : F ratio = 1 : 2.4). Histologically, 78.10% of cases were grade I, 19.20%
      were grade II, and 2.60% were grade III. Transitional variant was the most common
      (43.40%). VEGF expression (38.50% of cases) correlated positively with perifocal
      edema, tumor size, and proliferative index (PI). PR expression (64.5% of cases)
      correlated inversely with the PI (mean 3.75). Lymphocytic aggregates were
      detected in 7.20% of cases, with a mean CD20 : CD3 ratio of 1 : 10.1. In a
      multivariate analysis, only tumor size, PR expression and necrosis predicted
      recurrence independently. Using ROC curve, size was the best predictor of tumor
      recurrence with a cut-off point of >6 cm and an excellent negative predictive
      value (97.6%). CONCLUSIONS: Meningiomas in our region showed some distinctive
      clinicopathological and demographic criteria. Tumor size was found to be the best
      recurrence predictor factor of meningioma.

PMID- 24459429
TI  - A note on elongations of summable QTAG-modules.
AB  - A right module M over an associative ring with unity is a QTAG-module if every
      finitely generated submodule of any homomorphic image of M is a direct sum of
      uniserial modules. In this paper we find a suitable condition under which a
      special omega-elongation of a summable QTAG-module by a ( omega +k)-projective
      QTAG-module is also a summable QTAG-module. 

PMID- 24459430
TI  - Extracting product features and opinion words using pattern knowledge in customer
      reviews.
AB  - Due to the development of e-commerce and web technology, most of online Merchant
      sites are able to write comments about purchasing products for customer. Customer
      reviews expressed opinion about products or services which are collectively
      referred to as customer feedback data. Opinion extraction about products from
      customer reviews is becoming an interesting area of research and it is motivated
      to develop an automatic opinion mining application for users. Therefore,
      efficient method and techniques are needed to extract opinions from reviews. In
      this paper, we proposed a novel idea to find opinion words or phrases for each
      feature from customer reviews in an efficient way. Our focus in this paper is to
      get the patterns of opinion words/phrases about the feature of product from the
      review text through adjective, adverb, verb, and noun. The extracted features and
      opinions are useful for generating a meaningful summary that can provide
      significant informative resource to help the user as well as merchants to track
      the most suitable choice of product. 

PMID- 24459431
TI  - Expression and promoter analysis of six heat stress-inducible genes in rice.
AB  - During the long evolutionary process, plant gradually formed a series of
      strategies and mechanisms to cope with stress environment such as drought, heat,
      cold, and high salinity. Six highly heat responsive genes were identified in rice
      by microarray data analysis. The qRT-PCR analysis confirmed that the expression
      of these six genes were highly heat inducible and moderately responded to salt
      stress, polyethylene glycol, and abscisic acid treatment, but little affected by
      cold treatment. Promoters of the three highly heat-inducible genes (OsHsfB2cp,
      PM19p, and Hsp90p) were used to drive GUS gene expression in rice. The results of
      the GUS gene expression, histochemical staining, and GUS activities in panicles
      and flag leaves of the transgenic rice plants confirmed high heat-induced GUS
      activities and moderate drought-induced activities. The three promoters exhibited
      similar high activity lever in rice leaf under heat, but OsHsfB2cp and PM19p
      showed much higher activities in panicles under heat stress. Our work confirmed
      that the OsHsfB2c and PM19 promoters were highly heat inducible and further
      characterization and reconstruction of cis-elements in their promoters could lead
      to the development of highly effective heat-inducible promoters for plant genetic
      engineering. 

PMID- 24459432
TI  - Responses of ecosystem CO 2 fluxes to short-term experimental warming and
      nitrogen enrichment in an Alpine meadow, northern Tibet Plateau.
AB  - Over the past decades, the Tibetan Plateau has experienced pronounced warming,
      yet the extent to which warming will affect alpine ecosystems depends on how
      warming interacts with other influential global change factors, such as nitrogen
      (N) deposition. A long-term warming and N manipulation experiment was established
      to investigate the interactive effects of warming and N deposition on alpine
      meadow. Open-top chambers were used to simulate warming. N addition, warming, N
      addition * warming, and a control were set up. In OTCs, daytime air and soil
      temperature were warmed by 2.0 degrees C and 1.6 degrees C above ambient
      conditions, but soil moisture was decreased by 4.95 m(3) m(-3). N addition
      enhanced ecosystem respiration (Reco); nevertheless, warming significantly
      decreased Reco. The decline of Reco resulting from warming was cancelled out by N
      addition in late growing season. Our results suggested that N addition enhanced
      Reco by increasing soil N availability and plant production, whereas warming
      decreased Reco through lowering soil moisture, soil N supply potential, and
      suppression of plant activity. Furthermore, season-specific responses of Reco
      indicated that warming and N deposition caused by future global change may have
      complicated influence on carbon cycles in alpine ecosystems. 

PMID- 24459433
TI  - Advancements in n-type base crystalline silicon solar cells and their emergence
      in the photovoltaic industry.
AB  - The p-type crystalline silicon wafers have occupied most of the solar cell market
      today. However, modules made with n-type crystalline silicon wafers are actually
      the most efficient modules up to date. This is because the material properties
      offered by n-type crystalline silicon substrates are suitable for higher
      efficiencies. Properties such as the absence of boron-oxygen related defects and
      a greater tolerance to key metal impurities by n-type crystalline silicon
      substrates are major factors that underline the efficiency of n-type crystalline
      silicon wafer modules. The bi-facial design of n-type cells with good rear-side
      electronic and optical properties on an industrial scale can be shaped as well.
      Furthermore, the development in the industrialization of solar cell designs based
      on n-type crystalline silicon substrates also highlights its boost in the
      contributions to the photovoltaic industry. In this paper, a review of various
      solar cell structures that can be realized on n-type crystalline silicon
      substrates will be given. Moreover, the current standing of solar cell technology
      based on n-type substrates and its contribution in photovoltaic industry will
      also be discussed. 

PMID- 24459434
TI  - The influence of negative emotion on the Simon effect as reflected by p300.
AB  - The Simon effect refers to the phenomenon that reaction time (RT) is faster when
      stimulus and response location are congruent than when they are not. This study
      used the priming-target paradigm to explore the influence of induced negative
      emotion on the Simon effect with event-related potential techniques (ERPs). The
      priming stimuli were composed of two kinds of pictures, the negative and neutral
      pictures, selected from the International Affective Picture System (IAPS). The
      target stimuli included chessboards of two color types. One was red and black the
      other one was green and black. Each chessboard was presented on the left or the
      right of the screen. The participants were asked to press the response keys
      according to the colors of the chessboards. It was called the congruent condition
      if the chessboard and the response key were on the same side, otherwise
      incongruent condition. In this study, the emotion-priming Simon effect was found
      in terms of RT and P300. Negative emotion compared with neutral emotion
      significantly enhanced the Simon effect in the cognitive process, reflected by a
      larger difference of P300 latency between the incongruent and congruent trials.
      The results suggest that the induced negative emotion influenced the Simon effect
      at the late stage of the cognitive process, and the P300 latency could be
      considered as the reference measure. These findings may be beneficial to
      researches in psychology and industrial engineering in the future. 

PMID- 24459436
TI  - The generalization error bound for the multiclass analytical center classifier.
AB  - This paper presents the multiclass classifier based on analytical center of
      feasible space (MACM). This multiclass classifier is formulated as quadratic
      constrained linear optimization and does not need repeatedly constructing
      classifiers to separate a single class from all the others. Its generalization
      error upper bound is proved theoretically. The experiments on benchmark datasets
      validate the generalization performance of MACM. 

PMID- 24459435
TI  - Xeroderma pigmentosum: man deprived of his right to light.
AB  - Xeroderma pigmentosum (XP) is a hereditary autosomal recessive disorder
      characterized by photo hypersensitivity of sun exposed tissues and subsequent
      several-fold increased risk for malignant changes resulting from impaired ability
      to repair UV-induced DNA damage. Estimated incidences vary from 1 in 20,000 in
      Japan to 1 in 250,000 in the USA, and approximately 2.3 per million live births
      in Western Europe. Diagnosis is made clinically by the presence of unusual
      sunburns or lentiginosis or onset of cancers at an early age. It is confirmed by
      cellular tests for defective DNA repair. Although there is no cure for XP as of
      now, skin problems can be ameliorated with the use of sunscreens, sun avoidance
      methods, and recurrent tumor excisions. Oral isotretinoin and topical application
      of 5-fluorouracil to treat actinic keratoses are other therapeutic options. T4N5
      and photolyase liposomal lotions are innovations in the therapy of XP. Genetic
      counselling implicating the effect of consanguineous marriages should be
      considered in the management of XP patients. 

PMID- 24459437
TI  - Investigating the effect of lignosulfonate on erosion rate of the embankments
      constructed with clayey sand.
AB  - Internal erosion is known as the most important cause of dam failure after
      overtopping. It is important to improve the erosion resistance of the erodible
      soil by selecting an effective technique along with the reasonable costs. To
      prevent internal erosion of embankment dams the use of chemical stabilizers that
      reduce the soil erodibility potential is highly recommended. In the present
      study, a lignin-based chemical, known as lignosulfonate, is used to improve the
      erodibility of clayey sand specimen. The clayey sand was tested in various
      hydraulic heads in terms of internal erosion in its natural state as well as when
      it is mixed with the different percentages of lignosulfonate. The results show
      that erodibility of collected clayey sand is very high and is dramatically
      reduced by adding lignosulfonate. Adding 3% of lignosulfonate to clayey sand can
      reduce the coefficient of soil erosion from 0.01020 to 0.000017. It is also found
      that the qualitative erodibility of stabilized soil with 3% lignosulfonate is
      altered from the group of extremely rapid to the group of moderately slow. 

PMID- 24459438
TI  - Fungal and bacterial communities in the rhizosphere of Pinus tabulaeformis
      related to the restoration of plantations and natural secondary forests in the
      Loess Plateau, northwest China.
AB  - Chinese pine (Pinus tabulaeformis Carr.) is widely planted for restoration in
      destroyed ecosystems of the Loess Plateau in China. Although soil microbial
      communities are important subsurface components of the terrestrial ecosystems,
      little is known about fungal and bacterial communities in the rhizosphere of
      planted and natural P. tabulaeformis forests in the region. In this study, fungal
      and bacterial communities in the rhizosphere of P. tabulaeformis were analyzed by
      nested PCR-DGGE (denaturing gradient gel electrophoresis). Diversity analysis
      revealed that the values of the Shannon-Wiener index (H) and the Simpson index
      (D) of fungal communities were higher in natural secondary forests than in
      plantations except for the 3-year-old site. Moreover, the values of species
      richness, H, and D of the bacterial communities were also higher in the former.
      Totally, 18 fungal and 19 bacterial DGGE band types were successfully retrieved
      and sequenced. The dominant fungi in the rhizosphere of P. tabulaeformis belonged
      to the phylum of Basidiomycota, while the dominant bacteria belonged to the
      phylum of Proteobacteria. Principal component analysis indicated that fungal and
      bacterial species were more unitary in plantations than in natural secondary
      forests, and the majority of them were more likely to appear in the latter.
      Correlation analysis showed no significant correlation between the fungal and
      bacterial community diversities. 

PMID- 24459439
TI  - Integrated electrokinetics-adsorption remediation of saline-sodic soils: effects
      of voltage gradient and contaminant concentration on soil electrical
      conductivity.
AB  - In this study, an integrated in situ remediation technique which couples
      electrokinetics with adsorption, using locally produced granular activated carbon
      from date palm pits in the treatment zones that are installed directly to bracket
      the contaminated soils at bench-scale, is investigated. Natural saline-sodic clay
      soil, spiked with contaminant mixture (kerosene, phenol, Cr, Cd, Cu, Zn, Pb, and
      Hg), was used in this study to investigate the effects of voltage gradient,
      initial contaminant concentration, and polarity reversal rate on the soil
      electrical conductivity. Box-Behnken Design (BBD) was used for the experimental
      design and response surface methodology (RSM) was employed to model, optimize,
      and interpret the results obtained using Design-Expert version 8 platform. The
      total number of experiments conducted was 15 with voltage gradient, polarity
      reversal rate, and initial contaminant concentration as variables. The main
      target response discussed in this paper is the soil electrical conductivity due
      to its importance in electrokinetic remediation process. Responses obtained were
      fitted to quadratic models whose R (2) ranges from 84.66% to 99.19% with
      insignificant lack of fit in each case. Among the investigated factors, voltage
      gradient and initial contaminant concentration were found to be the most
      significant influential factors. 

PMID- 24459440
TI  - A novel coordinated edge caching with request filtration in radio access network.
AB  - Content caching at the base station of the Radio Access Network (RAN) is a way to
      reduce backhaul transmission and improve the quality of experience. So it is
      crucial to manage such massive microcaches to store the contents in a coordinated
      manner, in order to increase the overall mobile network capacity to support more
      number of requests. We achieve this goal in this paper with a novel caching
      scheme, which reduces the repeating traffic by request filtration and
      asynchronous multicast in a RAN. Request filtration can make the best use of the
      limited bandwidth and in turn ensure the good performance of the coordinated
      caching. Moreover, the storage at the mobile devices is also considered to be
      used to further reduce the backhaul traffic and improve the users' experience. In
      addition, we drive the optimal cache division in this paper with the aim of
      reducing the average latency user perceived. The simulation results show that the
      proposed scheme outperforms existing algorithms. 

PMID- 24459441
TI  - Substrate integrated waveguide cross-coupling filter with multilayer hexagonal
      cavity.
AB  - Hexagonal cavities and their applications to multilayer substrate integrated
      waveguide (SIW) filters are presented. The hexagonal SIW cavity which can combine
      flexibility of rectangular one and performance of circular one is convenient for
      bandpass filter's design. Three types of experimental configuration with the same
      central frequency of 10 GHz and bandwidth of 6%, including three-order and four
      order cross-coupling topologies, are constructed and fabricated based on low
      temperature cofired ceramic (LTCC) technology. Both theoretical and experimental
      results are presented.

PMID- 24459442
TI  - Prospective study on retinal nerve fibre layer thickness changes in isolated
      unilateral retrobulbar optic neuritis.
AB  - PURPOSE: To investigate the retinal nerve fibre layer (RNFL) thickness after
      unilateral acute optic neuritis using optical coherence tomography (OCT).
      PATIENTS AND METHODS: This prospective cohort study recruited consecutive
      patients with a first episode of isolated, unilateral acute optic neuritis. RNFL
      thickness and visual acuity (VA) of the attack and normal fellow eye were
      measured at presentation and 3 months in both the treatment and nontreatment
      groups. RESULTS: 11 subjects received systemic steroids and 9 were treated
      conservatively. The baseline RNFL thickness was similar in the attack and fellow
      eye (P >= 0.4). At 3 months, the attack eye had a thinner temporal (P = 0.02) and
      average (P = 0.05) RNFL compared to the fellow eye. At 3 months, the attack eye
      had significant RNFL thinning in the 4 quadrants and average thickness (P <=
      0.0002) compared to baseline. The RNFL thickness between the treatment and
      nontreatment groups was similar at baseline and 3 months (P >= 0.1). Treatment
      offered better VA at 3 months (0.1 +/- 0.2 versus 0.3 +/- 0.2 LogMAR, P = 0.04).
      CONCLUSION: Generalized RNFL thinning occurred at 3 months after a first episode
      of acute optic neuritis most significantly in the temporal quadrant and average
      thickness. Visual improvement with treatment was independent of RNFL thickness.

PMID- 24459443
TI  - Canine angiostrongylosis in naturally infected dogs: clinical approach and
      monitoring of infection after treatment.
AB  - Canine angiostrongylosis is an increasingly reported disease in Europe which can
      be fatal if left untreated. The wide range of clinical presentation along with
      the absence of pathognomonic alterations can make the diagnosis challenging; thus
      any additional information that may provide clues to an early diagnosis may be of
      value, in order to ensure adequate anthelmintic treatment. Aim of the study was
      to assess a clinicopathological scoring system associated with natural
      Angiostrongylus vasorum infection diagnosed in canine patients during clinical
      practice, to clinically and paraclinically monitor infected dogs after treatment,
      and to monitor the presence of L1 larvae in faecal samples by Baermann's test. Of
      the total 210 enrolled animals A. vasorum infection was diagnosed in 7 dogs.
      These dogs were clinically and paraclinically investigated and monitored after
      specific treatment. Further 3 symptomatic dogs were retrospectively included in
      the monitoring. Results suggest that the computed scoring system can help to
      increase the clinical suspicion of infection particularly in asymptomatic dogs
      before the onset of potentially lethal lesions. Data of faecal monitoring
      suggested that treatment may control parasite burden but be unable to eradicate
      infection. Thus, a continued faecal monitoring after treatment is advisable for
      identification of still infected or reinfected dogs. 

PMID- 24459444
TI  - CMOS: efficient clustered data monitoring in sensor networks.
AB  - Tiny and smart sensors enable applications that access a network of hundreds or
      thousands of sensors. Thus, recently, many researchers have paid attention to
      wireless sensor networks (WSNs). The limitation of energy is critical since most
      sensors are battery-powered and it is very difficult to replace batteries in
      cases that sensor networks are utilized outdoors. Data transmission between
      sensor nodes needs more energy than computation in a sensor node. In order to
      reduce the energy consumption of sensors, we present an approximate data
      gathering technique, called CMOS, based on the Kalman filter. The goal of CMOS is
      to efficiently obtain the sensor readings within a certain error bound. In our
      approach, spatially close sensors are grouped as a cluster. Since a cluster
      header generates approximate readings of member nodes, a user query can be
      answered efficiently using the cluster headers. In addition, we suggest an energy
      efficient clustering method to distribute the energy consumption of cluster
      headers. Our simulation results with synthetic data demonstrate the efficiency
      and accuracy of our proposed technique. 

PMID- 24459445
TI  - HPLC-DAD-ESI/MS identification of light harvesting and light screening pigments
      in the lake sediments at Edmonson Point.
AB  - The composition of sedimentary pigments in the Antarctic lake at Edmonson Point
      has been investigated and compared with the aim to provide a useful analytical
      method for pigments separation and identification, providing reference data for
      future assessment of possible changes in environmental conditions. Reversed phase
      high performance liquid chromatography (HPLC) with electrospray-mass spectrometry
      (ESI-MS) detection and diode array detection (DAD) has been used to identify
      light screening and light harvesting pigments. The results are discussed in terms
      of local environmental conditions. 

PMID- 24459446
TI  - A game theoretical model for location of terror response facilities under
      capacitated resources.
AB  - This paper is concerned with the effect of capacity constraints on the locations
      of terror response facilities. We assume that the state has limited resources,
      and multiple facilities may be involved in the response until the demand is
      satisfied consequently. We formulate a leader-follower game model between the
      state and the terrorist and prove the existence and uniqueness of the Nash
      equilibrium. An integer linear programming is proposed to obtain the equilibrium
      results when the facility number is fixed. The problem is demonstrated by a case
      study of the 19 districts of Shanghai, China. 

PMID- 24459447
TI  - Sensitivity analysis of mechanical parameters of different rock layers to the
      stability of coal roadway in soft rock strata.
AB  - According to the geological characteristics of Xinjiang Ili mine in western area
      of China, a physical model of interstratified strata composed of soft rock and
      hard coal seam was established. Selecting the tunnel position, deformation
      modulus, and strength parameters of each layer as influencing factors, the
      sensitivity coefficient of roadway deformation to each parameter was firstly
      analyzed based on a Mohr-Columb strain softening model and nonlinear elastic
      plastic finite element analysis. Then the effect laws of influencing factors
      which showed high sensitivity were further discussed. Finally, a regression model
      for the relationship between roadway displacements and multifactors was obtained
      by equivalent linear regression under multiple factors. The results show that the
      roadway deformation is highly sensitive to the depth of coal seam under the floor
      which should be considered in the layout of coal roadway; deformation modulus and
      strength of coal seam and floor have a great influence on the global stability of
      tunnel; on the contrary, roadway deformation is not sensitive to the mechanical
      parameters of soft roof; roadway deformation under random combinations of multi
      factors can be deduced by the regression model. These conclusions provide
      theoretical significance to the arrangement and stability maintenance of coal
      roadway. 

PMID- 24459448
TI  - Equilibrium and dynamic osmotic behaviour of aqueous solutions with varied
      concentration at constant and variable volume.
AB  - Osmosis is essential for the living organisms. In biological systems the process
      usually occurs in confined volumes and may express specific features. The osmotic
      pressure in aqueous solutions was studied here experimentally as a function of
      solute concentration (0.05-0.5 M) in two different regimes: of constant and
      variable solution volume. Sucrose, a biologically active substance, was chosen as
      a reference solute for the complex tests. A custom made osmotic cell was used. A
      novel operative experimental approach, employing limited variation of the
      solution volume, was developed and applied for the purpose. The established
      equilibrium values of the osmotic pressure are in agreement with the theoretical
      expectations and do not exhibit any evident differences for both regimes. In
      contrast, the obtained kinetic dependences reveal striking divergence in the
      rates of the process at constant and varied solution volume for the respective
      solute concentrations. The rise of pressure is much faster at constant solution
      volume, while the solvent influx is many times greater in the regime of variable
      volume. The results obtained suggest a feasible mechanism for the way in which
      the living cells rapidly achieve osmotic equilibrium upon changes in the
      environment.

PMID- 24459449
TI  - An interval-valued intuitionistic fuzzy TOPSIS method based on an improved score
      function.
AB  - This paper proposes an improved score function for the effective ranking order of
      interval-valued intuitionistic fuzzy sets (IVIFSs) and an interval-valued
      intuitionistic fuzzy TOPSIS method based on the score function to solve
      multicriteria decision-making problems in which all the preference information
      provided by decision-makers is expressed as interval-valued intuitionistic fuzzy
      decision matrices where each of the elements is characterized by IVIFS value and
      the information about criterion weights is known. We apply the proposed score
      function to calculate the separation measures of each alternative from the
      positive and negative ideal solutions to determine the relative closeness
      coefficients. According to the values of the closeness coefficients, the
      alternatives can be ranked and the most desirable one(s) can be selected in the
      decision-making process. Finally, two illustrative examples for multicriteria
      fuzzy decision-making problems of alternatives are used as a demonstration of the
      applications and the effectiveness of the proposed decision-making method. 

PMID- 24459450
TI  - The effects of salt on rheological properties of asphalt after long-term aging.
AB  - Limited studies in recent years have shown that asphalt pavement subject to
      seawater in coastal regions or deicing salt in cold regions may be seriously
      damaged after being soaked in saline water for a long time. However, there is
      limited research into the influence of salt on rheological properties of asphalt
      after long-term aging. In this study, rheological properties of unmodified and
      polymer-modified asphalt after long-term aging were tested after being soaked in
      different concentrations of salt (0.3%~5%) for different durations (1 day~30
      days). Orthogonal array based on the Taguchi method was used for experimental
      design. The frequency sweep tests were performed on the specimens of aged asphalt
      after being soaked for complex modulus and phase angle master curves and ultimate
      fatigue temperature. BBR tests were performed for stiffness. The test results
      indicate that saline water appears to reduce low temperature properties and
      fatigue resistance properties and improved high temperature properties of aged
      asphalt, and it also affects the sensitivity of complex modulus and phase angles
      at low frequencies. 

PMID- 24459451
TI  - UV-Initiated polymerization of cationic polyacrylamide: synthesis,
      characterization, and sludge dewatering performance.
AB  - P(AM-DAC-BA) was synthesized through copolymerization of acrylamide (AM),
      acryloyloxyethyl trimethyl ammonium chloride (DAC), and butylacrylate (BA) under
      ultraviolet (UV) initiation using response surface methodology (RSM). The
      influences of light intensity, illumination time, and photoinitiator
      concentration on the intrinsic viscosity [eta] of P(AM-DAC-BA) were investigated.
      RSM model based on the influencing data was established for optimizing synthetic
      conditions. It was found that, at light intensity 1491.67  MU w.cm(-2),
      illumination time 117.89 min, and photoinitiator concentration 0.600/00, there
      was a better material performance achieved. Thus P(AM-DAC-BA) prepared under the
      above conditions showed excellent dewatering performance that, with 40 mg.L(-1)
      P(AM-DAC-BA) at pH 7, the residual turbidity of supernatant and the dry solid
      content were up to 38 NTU, 28.5%, respectively. 

PMID- 24459452
TI  - A kernel-based approach for biomedical named entity recognition.
AB  - Support vector machine (SVM) is one of the popular machine learning techniques
      used in various text processing tasks including named entity recognition (NER).
      The performance of the SVM classifier largely depends on the appropriateness of
      the kernel function. In the last few years a number of task-specific kernel
      functions have been proposed and used in various text processing tasks, for
      example, string kernel, graph kernel, tree kernel and so on. So far very few
      efforts have been devoted to the development of NER task specific kernel. In the
      literature we found that the tree kernel has been used in NER task only for
      entity boundary detection or reannotation. The conventional tree kernel is unable
      to execute the complete NER task on its own. In this paper we have proposed a
      kernel function, motivated by the tree kernel, which is able to perform the
      complete NER task. To examine the effectiveness of the proposed kernel, we have
      applied the kernel function on the openly available JNLPBA 2004 data. Our kernel
      executes the complete NER task and achieves reasonable accuracy. 

PMID- 24459453
TI  - Development of inspection robots for bridge cables.
AB  - This paper presents the bridge cable inspection robot developed in Korea. Two
      types of the cable inspection robots were developed for cable-suspension bridges
      and cable-stayed bridge. The design of the robot system and performance of the
      NDT techniques associated with the cable inspection robot are discussed. A review
      on recent advances in emerging robot-based inspection technologies for bridge
      cables and current bridge cable inspection methods is also presented. 

PMID- 24459454
TI  - Properties of spent active coke particles analysed via comminution in spouted
      bed.
AB  - Samples of active coke, fresh and spent after cleaning flue gases from communal
      waste incinerators, were investigated. The outer layers of both coke particles
      were separately removed by comminution in a spouted bed. The samples of both
      active cokes were analysed by means of densities, mercury porosimetry, and
      adsorption technique. Remaining cores were examined to determine the degree of
      consumption of coke by the sorption of hazardous emissions (SO2, HCl, and heavy
      metals) through its bed. Differences in contamination levels within the porous
      structure of the particles were estimated. The study demonstrated the
      effectiveness of commercial active coke in the cleaning of flue gases. 

PMID- 24459455
TI  - Molecular detection of porcine torovirus in piglets with diarrhea in southwest
      China.
AB  - Porcine torovirus (PToV) was detected from intestinal samples of piglets with
      diarrhea from 20 farms in southwest China. The total prevalence of PToV was 45%
      (9 out of 20 farms); it was the first detection of PToV in China, and also the
      study analyzed the phylogenetic relationships between the Chinese PToV and PToV
      reference strains as well as other representative toroviruses. Genetic and
      phylogenetic analysis showed the existence of genetic diversity among
      geographically separated PToV. Statistical analysis of the PToV positive rate as
      well as a survey for other enteric pathogens in diarrheic pigs suggests that PToV
      may play a role as a causative agent of severe diarrhea in piglets. 

PMID- 24459456
TI  - Trends in female representation in published ophthalmology literature, 2000-2009.
AB  - PURPOSE: To examine trends in female first and last authors in clinical
      ophthalmology literature published from January 2000 to December 2009. METHODS: A
      total of 3760 articles in American Journal of Ophthalmology (AJO), 2347 articles
      in Archives of Ophthalmology (Archives), and 3838 articles in Ophthalmology
      spanning 10 years of published ophthalmology peer-reviewed literature were
      examined. All original research articles and brief reports indexed online were
      included. Author gender was determined by an exhaustive Internet search. Articles
      were excluded if the sex of the author could not be determined or was not
      applicable (for example, articles by a study group rather than an individual
      author). RESULTS: Gender information was identified in 86.8% of articles for
      first authors and 86% for last authors. The number of female first authors (P <
      0.0001) and last authors (P = 0.005) increased significantly in the study period
      in all journals examined, with a significant association between the sex of the
      first and last authors (OR = 2.19; 95% CI, 1.96-2.46; P < 0.0001), when examining
      all articles. Female representation increased for last authors significantly only
      in Ophthalmology. There was a significant correlation between gender of the first
      author and total number of authors that was not observed with last-author sex.
      CONCLUSIONS: Female first authorship has increased from 2000 to 2009 and is
      correlated with the gender of the last author; however, there were fewer female
      last authors compared to female first authors in the same period.

PMID- 24459457
TI  - Cystoid macular edema associated with acitretin.
AB  - Cystoid macular edema represents a "final common pathway" response of the retina
      to a variety of insults. It has been reported in association with vascular
      problems, inflammatory conditions, inherited diseases, tractional problems,
      intraocular surgery and medications. We report a case of cystoid macular edema
      associated with acitretin in a 65-year-old woman and document its resolution with
      optical coherence tomography (OCT). 

PMID- 24459458
TI  - Value of anti-VEGF treatment in choroidal neovascularization associated with
      autosomal recessive bestrophinopathy.
AB  - A 26-year-old white woman presented with a 1-year history of reduced vision in
      both eyes, bilateral yellowish deposits in the central macula, and pale yellow
      retinal flecks extending to midretinal periphery. Choroidal neovascularization
      (CNV) was confirmed in her left eye. On optical coherence tomography, both eyes
      showed diffuse intraretinal cystic spaces, thickening and separation of the
      photoreceptor layer from the retinal pigment epithelium (RPE), subretinal fluid,
      and focal thickening at the level of the RPE at the fovea. A diagnosis of
      autosomal recessive bestrophinopathy was confirmed by electrodiagnostic and
      molecular genetics testing. The CNV responded well to intravitreal ranibizumab
      therapy, and visual acuity in the left eye improved and stabilized; however,
      retinoschisis due to fluctuations in intraretinal fluid persisted. This case
      highlights the fact that current optical coherence tomography-driven protocols
      used widely to treat neovascular age-related macular degeneration may not be
      appropriate for CNV associated with other retinal diseases. 

PMID- 24459459
TI  - A 50-year-old man with a long-standing, large-angle exotropia and limitation of
      adduction in the left eye.

PMID- 24459461
TI  - Elastography: general principles and clincial applications.

PMID- 24459460
TI  - Force Field for Peptides and Proteins based on the Classical Drude Oscillator.
AB  - Presented is a polarizable force field based on a classical Drude oscillator
      framework, currently implemented in the programs CHARMM and NAMD, for modeling
      and molecular dynamics (MD) simulation studies of peptides and proteins. Building
      upon parameters for model compounds representative of the functional groups in
      proteins, the development of the force field focused on the optimization of the
      parameters for the polypeptide backbone and the connectivity between the backbone
      and side chains. Optimization of the backbone electrostatic parameters targeted
      quantum mechanical conformational energies, interactions with water, molecular
      dipole moments and polarizabilities and experimental condensed phase data for
      short polypeptides such as (Ala)5. Additional optimization of the backbone phi,
      psi conformational preferences included adjustments of the tabulated two
      dimensional spline function through the CMAP term. Validation of the model
      included simulations of a collection of peptides and proteins. This 1st
      generation polarizable model is shown to maintain the folded state of the studied
      systems on the 100 ns timescale in explicit solvent MD simulations. The Drude
      model typically yields larger RMS differences as compared to the additive
      CHARMM36 force field (C36) and shows additional flexibility as compared to the
      additive model. Comparison with NMR chemical shift data shows a small degradation
      of the polarizable model with respect to the additive, though the level of
      agreement may be considered satisfactory, while for residues shown to have
      significantly underestimated S2 order parameters in the additive model,
      improvements are calculated with the polarizable model. Analysis of dipole
      moments associated with the peptide backbone and tryptophan side chains show the
      Drude model to have significantly larger values than those present in C36, with
      the dipole moments of the peptide backbone enhanced to a greater extent in sheets
      versus helices and the dipoles of individual moieties observed to undergo
      significant variations during the MD simulations. Although there are still some
      limitations, the presented model, termed Drude-2013, is anticipated to yield a
      molecular picture of peptide and protein structure and function that will be of
      increased physical validity and internal consistency in a computationally
      accessible fashion.

PMID- 24459462
TI  - A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in
      Children with Autism via Transcranial Ultrasonography.
AB  - BACKGROUND: Autism spectrum disorders (ASDs) are developmental conditions of
      uncertain etiology which have now affected more than 1% of the school-age
      population of children in many developed nations. Transcranial ultrasonography
      (TUS) via the temporal bone appeared to be a potential window of investigation to
      determine the presence of both cortical abnormalities and increased extra-axial
      fluid (EAF). METHODS: TUS was accomplished using a linear probe (10-5 MHz).
      Parents volunteered ASD subjects (N = 23; males 18, females 5) for evaluations
      (mean = 7.46 years +/- 3.97 years), and 15 neurotypical siblings were also
      examined (mean = 7.15 years +/- 4.49 years). Childhood Autism Rating Scale
      (CARS2((r))) scores were obtained and the ASD score mean was 48.08 + 6.79
      (Severe). RESULTS: Comparisons of the extra-axial spaces indicated increases in
      the ASD subjects. For EAF we scored based on the gyral summit distances between
      the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05
      cm, (2) 0.05-0.07 cm, (3) 0.08-0.10 cm, (4) >0.10 cm. All of the neurotypical
      siblings scored 1, whereas the ASD mean score was 3.41 +/- 0.67. We also defined
      cortical dysplasia as the following: hypoechoic lesions within the substance of
      the cortex, or disturbed layering within the gray matter. For cortical dysplasia
      we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly
      atypical cortical layering patterns, (3) more common, but separated areas of
      cortical hypoechogenic lesions, (4) very common or confluent areas of cortical
      hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD
      subjects' mean score was 2.79 +/- 0.93. CONCLUSION: TUS may be a useful screening
      technique for children at potential risk of ASDs which, if confirmed with
      repeated studies and high resolution MRI, provides rapid, non-invasive
      qualification of EAF, and cortical lesions.

PMID- 24459463
TI  - Modulation of Intestinal TLR4-Inflammatory Signaling Pathways by Probiotic
      Microorganisms: Lessons Learned from Lactobacillus jensenii TL2937.
AB  - The intestinal mucosa plays a critical role in the host's interactions with
      innocuous commensal microbiota and invading pathogenic microorganisms. Intestinal
      epithelial cells (IECs) and gut associated immune cells recognize the bacterial
      components via pattern-recognition receptors (PRRs) and are responsible for
      maintaining tolerance to the large communities of resident luminal bacteria while
      being also able to mount inflammatory responses against pathogens. Toll-like
      receptors (TLRs) are a major class of PRRs that are present on IECs and immune
      cells which are involved in the induction of both tolerance and inflammation. A
      growing body of experimental and clinical evidence supports the therapeutic and
      preventive application of probiotics for several gastrointestinal inflammatory
      disorders in which TLRs exert a significant role. This review aims to summarize
      the current knowledge of the beneficial effects of probiotic microorganisms with
      the capacity to modulate the immune system (immunobiotics) in the regulation of
      intestinal inflammation in pigs, which are very important as both livestock and
      human model. Especially we discuss the role of TLRs, their signaling pathways,
      and their negative regulators in both the inflammatory intestinal injury and the
      beneficial effects of immunobiotics in general, and Lactobacillus jensenii TL2937
      in particular. This review article emphasizes the cellular and molecular
      interactions of immunobiotics with IECs and immune cells through TLRs and their
      application for improving animal and human health. 

PMID- 24459464
TI  - An N-Terminal Missense Mutation in STX11 Causative of FHL4 Abrogates Syntaxin-11
      Binding to Munc18-2.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is an often-fatal
      hyperinflammatory disorder caused by autosomal recessive mutations in PRF1,
      UNC13D, STX11, and STXBP2. We identified a homozygous STX11 mutation, c.173T > C
      (p.L58P), in three patients presenting clinically with hemophagocytic
      lymphohistiocytosis from unrelated Pakistani families. The mutation yields an
      amino acid substitution in the N-terminal Habc domain of syntaxin-11 and resulted
      in defective natural killer cell degranulation. Notably, syntaxin-11 expression
      was decreased in patient cells. However, in an ectopic expression system,
      syntaxin-11 L58P was expressed at levels comparable to wild-type syntaxin-11, but
      did not bind Munc18-2. Moreover, another N-terminal syntaxin-11 mutant, R4A, also
      did not bind Munc18-2. Thus, we have identified a novel missense STX11 mutation
      causative of FHL type 4. The syntaxin-11 R4A and L58P mutations reveal that both
      the N-terminus and Habc domain of syntaxin-11 are required for binding to Munc18
      2, implying similarity to the dynamic binary binding of neuronal syntaxin-1 to
      Munc18-1. 

PMID- 24459465
TI  - Neurotrophins differentially stimulate the growth of cochlear neurites on
      collagen surfaces and in gels.
AB  - The electrodes of a cochlear implant are located far from the surviving neurons
      of the spiral ganglion, which results in decreased precision of neural activation
      compared to the normal ear. If the neurons could be induced to extend neurites
      toward the implant, it might be possible to stimulate more discrete
      subpopulations of neurons, and to increase the resolution of the device. However,
      a major barrier to neurite growth toward a cochlear implant is the fluid filling
      the scala tympani, which separates the neurons from the electrodes. The goal of
      this study was to evaluate the growth of cochlear neurites in three-dimensional
      extracellular matrix molecule gels, and to increase biocompatibility by using
      fibroblasts stably transfected to produce neurotrophin-3 and brain-derived
      neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated
      in cultures. They were exposed to soluble neurotrophins, cells transfected to
      secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew
      readily on collagen surfaces and in three-dimensional collagen gels. Co-culture
      with cells producing neurotrophin-3 resulted in increased numbers of neurites,
      and neurites that were longer than when explants were cultured with control
      fibroblasts stably transfected with green fluorescent protein. Brain-derived
      neurotrophic factor-producing cells resulted in a more dramatic increase in the
      number of neurites, but there was no significant effect on neurite length. It is
      suggested that extracellular matrix molecule gels and cells transfected to
      produce neurotrophins offer an opportunity to attract spiral ganglion neurites
      toward a cochlear implant.

PMID- 24459466
TI  - A regression approach to ROC surface, with applications to Alzheimer's disease.
AB  - We consider the estimation of three-dimensional ROC surfaces for continuous tests
      given covariates. Three way ROC analysis is important in our motivating example
      where patients with Alzheimer's disease are usually classified into three
      categories and should receive different category-specific medical treatment.
      There has been no discussion on how covariates affect the three way ROC analysis.
      We propose a regression framework induced from the relationship between test
      results and covariates. We consider several practical cases and the corresponding
      inference procedures. Simulations are conducted to validate our methodology. The
      application on the motivating example illustrates clearly the age and sex effects
      on the accuracy for Mini-Mental State Examination of Alzheimer's disease.

PMID- 24459467
TI  - Hormonal modulation in aging patients with erectile dysfunction and metabolic
      syndrome.
AB  - Erectile dysfunction (ED), metabolic syndrome (MetS), and hypogonadism are
      closely related, often coexisting in the aging male. Obesity was shown to raise
      the risk of ED and hypogonadism, as well as other endocrinological disturbances
      with impact on erectile function. We selected 179 patients referred for ED to our
      andrology unit, aiming to evaluate gonadotropins and estradiol interplay in
      context of ED, MetS, and hypogonadism. Patients were stratified into groups in
      accordance with the presence (or not) of MetS and/or hypogonadism. Noticeable
      differences in total testosterone (TT) and free testosterone (FT) levels were
      found between patients with and without MetS. Men with MetS evidenced lower TT
      circulating levels with an increasing number of MetS parameters, for which
      hypertriglyceridemia and waist circumference strongly contributed. Regarding the
      hypothalamic-pituitary-gonadal axis, patients with hypogonadism did not exhibit
      raised LH levels. Interestingly, among those with higher LH levels, estradiol
      values were also increased. Possible explanations for this unexpected profile of
      estradiol may be the age-related adiposity, other estrogen-raising pathways, or
      even unknown mechanisms. Estradiol is possibly a molecule with further
      interactions beyond the currently described. Our results further enlighten this
      still unclear multidisciplinary and complex subject, raising new investigational
      opportunities. 

PMID- 24459468
TI  - Vitamin d and kidney.

PMID- 24459469
TI  - First trimester typhoid Fever with vertical transmission of salmonella typhi, an
      intracellular organism.
AB  - We report a case in which placental abruption occurred at 16 weeks following
      first trimester diagnosis and treatment for typhoid fever. Unexpectedly
      Salmonella enterica serovar Typhi (S. Typhi) was found in fetal tissues at
      autopsy. Using information from the murine model of typhoid fever in pregnancy,
      we draw parallels between S. Typhi and L. monocytogenes to develop a plausible
      hypothesis to explain how this organism was able to cross the placenta in the
      first trimester to cause abruption, inflammation, and expulsion of the fetus and
      placenta. We hope that this model for understanding placental infections by the
      hematogenous route helps to raise awareness that organisms not typically
      associated with TORCH infection can nevertheless cause placental infection and
      pregnancy loss. 

PMID- 24459470
TI  - Effects of Carum carvi L. (Caraway) extract and essential oil on TNBS-induced
      colitis in rats.
AB  - Carum carvi L. (Apiaceae family) or caraway is a common household plant grown
      around the world including Iran. Caraway fruits are used as flavoring agent in
      foods and beverages, and have various traditional uses in ethnomedicine. Anti
      inflammatory, spasmolytic, antimicrobial, antioxidant, carminative and
      immunomodulatory properties of caraway suggest that it might exert beneficial
      effects on inflammatory bowel disease (IBD). Therefore, this study was carried
      out to investigate the effects of caraway hydroalcoholic extract (CHE) and its
      essential oil (CEO) in an immunological model of colitis in rats induced by
      trinitrobenzene sulfonic acid (TNBS). Different doses of CHE (100, 200, 400
      mg/kg) and CEO (100, 200, 400 MUl/kg) were administered orally (p.o.) and also
      doses of CHE (100, 400 mg/kg) and CEO (100, 400 MUl/kg) were given
      intraperitoneally (i.p.) to the separate groups of male Wistar rats (n=6).
      Administration of the doses started 6 h after induction of colitis and continued
      daily for 5 consecutive days. Wet colon weight/length ratio was measured and
      tissue damage scores as well as indices of colitis were evaluated both
      macroscopically and histopathologically. CHE and CEO at all doses tested were
      effective in reducing colon tissue lesions and colitis indices and the efficacy
      was nearly the same when different doses of plant fractions were administered
      p.o. or i.p. Administration of prednisolone (p.o., 4 mg/kg), Asacol(r)
      (mesalazine microgranules, p.o., 100 mg/kg) and hydrocortisone acetate (i.p., 20
      mg/kg) as references were effective in reducing colon tissue injures as well.
      These data suggest that caraway fractions are both effective and possess anti
      colitic activity irrespective of the dose and route of administration. 

PMID- 24459471
TI  - Expression of the recombinant plasminogen activator (reteplase) by a non-lytic
      insect cell expression system.
AB  - Reteplase is a potent thrombolytic agent which is widely used in the management
      of acute myocardial infarction and stroke. It belongs to the third generation of
      the thrombolytic drugs and has been derived from native human tissue plasminogen
      activator by removing three domains of it and keeping the Kringle 2 and Serine
      protease domains. However, the high cost of this drug, has limited the
      application of this drug especially in the developing and third world countries.
      The most laborious steps in the bacterial production of this drug is its
      purification and refolding steps which keep the process yield low and the cost
      high. Therefore, in the present study we evaluated the expression of reteplase by
      a non-lytic insect cell expression system. Following cloning and transfection
      procedures, recombinant Sf9 insect cell clones expressing the reteplase protein
      were selected. Primarily, the expression was verified by dot-blot analysis and
      subsequently it was confirmed by Western Blotting showing a band of about 45 kD
      on nitrocellulose membrane. The biological activity of the expressed protein was
      also evaluated and showed to be about 29 IU/ml. This confirmed the possibility of
      expression and the correct folding of the expressed protein. Hence, optimization
      of the expression followed by purification of the protein could be the next steps
      of the study. 

PMID- 24459472
TI  - Inhibitory effect of Rosa damascena Mill flower essential oil, geraniol and
      citronellol on rat ileum contraction.
AB  - Flower of Rosa damascena Mill is widely used in Iran for gastrointestinal (GI)
      disorders. However, its pharmacological action on ileum contraction has not been
      studied. In this research we have investigated ileum motility effect of essential
      oil of flower petals of R. damascena growing in Kashan, Iran, and two of its
      constituents. The essential oils obtained by hydrodistillation were investigated
      by a combination of GC and GC/MS. More than 34 compounds have been identified.
      The main constituents of the essential oil were beta-citronellol (23%),
      nonadecane (16%), geraniol (16%) and heneicosane (5%). A portion of rat isolated
      ileum was suspended under 1g tension in Tyrode's solution at 37 degrees C and
      gassed with O2. Effect of the R. damascena essential oil (2.5-160 MUg/ml),
      geraniol (0.2-3.2 MUg/ml) and citronellol (0.8-6.4 MUg/ml) were studied on ileum
      contractions induced by KCl, acetylcholine (ACh) and electrical field stimulation
      (EFS) and compared with standard drugs atropine and loperamide. The contractile
      response of EFS was mediated mainly through the intramural nerve plexuses,
      because its response was inhibited by loperamide and partially reduced by
      atropine. The essential oil concentration dependently inhibited the response to
      KCl (IC50=67 +/- 8.4MUg/ml) and EFS (IC50=47 +/- 10.6 MUg/ml). Geraniol (IC50=1.7
      +/- 0.15 MUg/ml for KCl) and citronellol (IC50=2.9 +/- 0.3 MUg/ml for KCl) also
      had inhibitory effect of ileum contraction and both were more potent than the
      essential oil. It was concluded that R. damascena essential oil mainly had an
      inhibitory effect on ileum contractions and geraniol and citronellol had a major
      role in inhibitory effect of the essential. 

PMID- 24459473
TI  - Preparation and assessment of chitosan-coated superparamagnetic Fe3O4
      nanoparticles for controlled delivery of methotrexate.
AB  - In this study, Fe3O4 superparamagnetic nanoparticles were synthesized and
      stabilized by chitosan. Then the nanoparticles were characterized by Fourier
      transform infrared spectroscopy and transmission electron microscopy (TEM).
      Particle size distribution and Zeta potential of the particles also was assessed
      using Malvern Zetasizer. The paramagnetic behaviors of the uncoated and chitosan
      coated nanoparticles were measured using vibrating scanning magnetometry
      Particles morphology and size ranges of uncoated iron oxide nanoparticles were
      evaluated by TEM, showing uniform and narrow size distribution about 10 nm. After
      coating nanoparticles with chitosan and loading of methotrexate (MTX), the change
      in size was assessed using Zetasizer. Considerable increase in size was observed
      following the coating of the particles with chitosan and loading with MTX (the
      average size was 152 nm). Paramagnetic properties of the uncoated and chitosan
      coated particles were assessed showing significant decrease in paramagnetic
      behavior after coating with chitosan, but it was enough to respond to the
      magnetic field. Finally loading efficiency, release rate and cytotoxicity of MTX
      were assessed indicating slow release behavior with the same levels of cell
      toxicity in SK-BR-3 cell lines, suggesting this formulation as a good candidate
      for the controlled delivery of MTX. 

PMID- 24459474
TI  - Isolation and characterization of steroids, phthalide and essential oil of the
      fruits of Kelussia odoratissima Mozaff., an endemic mountain celery.
AB  - Kelussia odoratissima Mozaff. is an Iranian endangered endemic edible plant with
      enormous use in the middle region of Iran as food and spice especially yogurt
      seasoning, and as medicinal herb for anti-inflammatory and cardiovascular
      purposes. Although antioxidant, anti-inflammatory and antilipidemic effects of
      this plant have so far been studied, but chemical analyses of the non volatile
      constituents of the plant have not yet been reported. Therefore, identification
      of chemical constituents of different parts of plant was investigated in the
      present study. In this direction, two steroids including stigmasterol and beta
      sitosterol and one phthalide namely 3-butyliden-4,5-dihydrophthalide were
      isolated from the plant fruits. In addition, the essential oil composition of the
      fruits was studied. Thirty eight compounds were identified, of which the major
      components were found to be Z-ligustilide (29.2%), germacrene-B (15.9%) and
      germacrene-D (15.5%). According to the previous bioassays of the isolated
      compounds such as anti-inflammatory and anti-lipidemic effects of phthalides and
      steroids, a chemical-biological relation can be postulated. 

PMID- 24459475
TI  - Comparison of bleomycin-induced pulmonary apoptosis between NMRI mice and C57BL/6
      mice.
AB  - Apoptosis has a critical role in the pathogenesis of bleomycin induced-pulmonary
      fibrosis. The severity of fibrosis varies among different strains of mice. Recent
      studies have indicated that expression of apoptotic regulatory genes may be
      specific in different cell types in various strains. In this study, bleomycin
      induced pulmonary apoptosis in NMRI (Naval Medical Research Institute, USA)
      albino mice were compared with C57BL/6 black mice. Pulmonary fibrosis induced by
      single intratracheal administration of bleomycin (3 U/kg). Control mice were
      instilled with the same volume of saline. After 2 weeks, fibrotic responses were
      studied by biochemical measurement of collagen deposition and histological
      examination of pathological lung changes. Apoptosis was detected and quantitated
      by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      assay. Bleomycin significantly (P<0.05) increased lung collagen content and also
      induced fibrotic histological changes in both strains. Apoptosis was detected in
      the bronchiolar and alveolar epithelial cells after bleomycin instillation. TUNEL
      positive alveolar epithelial cells in bleomycin-treated lungs of C57BL/6 and NMRI
      mice (19.5% + 2.7 and 17% + 2.0, respectively) were significantly (P<0.05) higher
      than that of saline-treated lungs (1.5% + 0.5) with no significant difference
      between two strains of mice (P>0.05). Despite some murine strain variation in the
      expression of apoptotic regulatory genes in bleomycin-induced pulmonary fibrosis,
      the results of the present study revealed no significant differences in alveolar
      epithelial apoptosis between NMRI and C57BL/6 black mice. However, these results
      confirm the role of apoptosis in the pathogenesis of pulmonary fibrosis and
      suitability of both strains as experimental models of lung fibrosis. 

PMID- 24459476
TI  - Heavy metal contamination of vegetables in Isfahan, Iran.
AB  - Vegetables are an inevitable and important part of a healthy and balanced diet.
      They could be contaminated by heavy metals in many ways including irrigation by
      sewage water and industrial effluents sewage sludge, vehicular emissions,
      industrial waste and atmospheric deposition. In this study, we sought to
      determine if some vegetables (cucumbers, tomatoes, cabbage, lettuce, potatoes,
      onions, carrots, persian leeks, dill, spinach, coriander, parsley) grown locally
      in the suburban of Isfahan city and sold in the urban markets are contaminated
      with cadmium (Cd), chromium (Cr) and lead (Pb). Vegetables were sampled from
      August to October 2010. After washing, they were oven-dried and digested using
      three-acid mixture (70% HNO3, 65% HClO4 and 70% H2SO4). Analyzes of the heavy
      metals was performed using atomic absorption spectrophotometry. To validate the
      assay method, intra-day and inter-day variation studies were performed. The
      concentrations (MUg/g) of heavy metals in the samples ranged from 0.00 to 3.66
      for Cd, 0.00 to 6.00 for Cr and 0.00 to 7.14 for Pb. The highest concentration of
      heavy metals was for Pb. The results showed that the amount of Cd, Cr and Pb of
      some samples exceeded the recommended levels. The amount of Cd in cucumber,
      tomatoes, potatoes with skin, carrots, and spinach was significantly higher in
      the samples collected from Isfahanak, Dashti and Ilchi farms than those of Dorche
      farms. Also, the amount of Cr in onion, carrots, and spinach was significantly
      higher in samples collected from Isfahanak, Dashti and Ilchi farms than those of
      Dorche farms. However, the amount of Pb in the carrots and leek was significantly
      higher in the samples collected from Dorche farms than those of Isfahanak, Dashti
      and Ilchi farms. It can be concluded from the findings of this study that the
      amounts of Cd, Cr, and Pb were higher than the acceptable levels recommended by
      WHO/FAO. Also, higher amount of Cd and Cr in some samples collected from
      Isfahanak, Dashti and Ilchi farms compared to that of the samples collected from
      Dorche farms may indicate the influence of contaminants that enter ZayadeRood
      River as it passes Isfahan. 

PMID- 24459477
TI  - The effect of AM281, a cannabinoid antagonist, on memory performance during
      spontaneous morphine withdrawal in mice.
AB  - Abrupt cessation of morphine leads to withdrawal signs and cognitive deficits.
      Endocannabinoid system is activated during withdrawal; therefore, the aim of the
      present study was to assess the effects of AM281, cannabinoid antagonist/inverse
      agonist, on memory deficit following spontaneous morphine withdrawal. Cognition
      was evaluated by using the object recognition task. The novel object recognition
      task was tested in a square wooden open-field box using objects. The test was
      consisting of three sections: 15 min exploration, first trial for 12 min and
      second one for 5 min. In the second trial the difference in exploration between a
      previously seen object and a novel one, was considered as an index of memory
      performance (recognition index - RI). Male mice were made dependent by increasing
      doses of morphine (30-90 mg/kg) subcutaneously twice daily for 3 days. AM281
      (0.62, 1.25 and 2.5 mg/kg) were used in chronic form concurrent with morphine
      i.p. or acutely (2.5, 5 and 10 mg/kg) on the last day. RI was evaluated on the
      third day 4 h after the last dose of morphine. Chronic administration of AM281 at
      2.5 mg/kg improved RI to the 22.1 +/- 4.8 and single dose of AM281 at 5 mg/kg
      improved the memory impairment to the 8.5 +/- 4, as compared with vehicle-treated
      which was 4.8 +/- 2.5. The results suggested that administration of AM281 at a
      dose of 2.5 mg/kg in chronic form and 5 mg/kg in acute dose improved memory. 

PMID- 24459478
TI  - Chemical composition and general toxicity of essential oils extracted from the
      aerial parts of Artemisia armeniaca Lam. and A. incana (L.) Druce growing in
      Iran.
AB  - The essential oils of the aerial parts of A. armeniaca and A. incana, collected
      from Arasbaran area (East Azarbaijan province, Iran) were extracted by
      hydrodistillation and analyzed by GC-MS. In total, 16 and 40 constituents were
      identified and quantified in the oils of A. armeniaca and A. incana representing
      80.5% and 84.6% of the oils, respectively. The essential oil of A. armeniaca was
      mainly composed of non-terpene hydrocarbons (24.8%). The major components of the
      oil were alpha-pinene (10.7%), nonadecane (10.0%), 6,10,14-trimethyl-2
      pentadecanone (9.4%), spathulenol (7.8%) and Z-verbenol (5.8%). The essential oil
      of A. incana was dominated by oxygenated monoterpenes (41.6%), with camphor
      (20.4%), 1,8-cineol (10.3%), Z-verbenol (8.7%), beta-thujone (8.3%) and alpha
      thujone (5.6%), as major components. The essential oils were also subjected to
      general toxicity assay using brine shrimp lethality method. The toxicity profile
      of both oils indicated some degree of toxicity in comparison with
      podophyllotoxin. 

PMID- 24459479
TI  - Nitric oxide synthesis in the adult and developing kidney.
AB  - Nitric oxide (NO) is synthesized within the adult and developing kidney and plays
      a critical role in the regulation of renal hemodynamics and tubule function. In
      the adult kidney, the regulation of NO synthesis is very cell type specific and
      subject to distinct control mechanisms of NO synthase (NOS) isoforms. Endothelial
      NOS (eNOS) is expressed in the endothelial cells of glomeruli, peritubular
      capillaries, and vascular bundles. Neuronal NOS (nNOS) is expressed in the
      tubular epithelial cells of the macula densa and inner medullary collecting duct.
      Furthermore, in the immature kidney, the expression of eNOS and nNOS shows unique
      patterns distinct from that is observed in the adult. This review will summarize
      the localization and presumable function of NOS isoforms in the adult and
      developing kidney. 

PMID- 24459481
TI  - Long-Term Regulation of Renal Urea Transporters during Antidiuresis.
AB  - To produce a concentrated urine, the renal medulla needs hypertonicity for the
      reabsorption of free water from collecting duct. The single effect that increases
      interstitial tonicity in the outer medulla is the active NaCl reabsorption in the
      thick ascending limb, while the single effect in the inner medulla is the passive
      efflux of NaCl through the thin ascending limb. The passive mechanism in the
      inner medulla requires high interstitial urea concentration. Two main groups of
      urea transporters (UT-A, UT-B) are present in the kidney, which maintains the
      high concentration of urea in the deepest portion of the inner medulla by intra
      renal urea recycling. Recent studies suggest that UT-A1 in the terminal inner
      medullary collecting duct is up-regulated when urine or inner medullary
      interstitial urea is depleted in order to enhance the reabsorption of urea, while
      UT-A2 in the descending thin limb of loops of Henle and UT-B in the descending
      vasa recta are increased when outer medullary interstitial urea concentration is
      high, in order to prevent the loss of urea from the medulla to the systemic
      circulation, thereby increasing intra-renal urea recycling. This review will
      summarize the functions of the renal urea transporters in urine concentration
      mechanism and the recent knowledge about their long-term regulation. 

PMID- 24459480
TI  - Introduction of Organic Anion Transporters (SLC22A) and a Regulatory Mechanism by
      Caveolins.
AB  - The kidney is an important organ for controlling the volume of body fluids,
      electrolytic balance and excretion/reabsorption of endogenous and exogenous
      compounds. Among these renal functions, excretion/reabsorption of endogenous and
      exogenous substance is very important for the maintenance of physiological
      homeostasis in the body. Recently discovered organic anion transporters (OAT or
      SLC22A) have important roles for renal functions. It is well known as drug
      transporter. Several isoforms belong to SLC22A family. They showed different
      transport substrate spectrums and different localizations within the kidney.
      Their gene expressions are changed by some stimulus. The functional transport
      properties are regulated by protein kinase C. In addition, the function of
      organic anion transporters are also regulated by protein-protein interaction,
      such as caveolin which is compositional protein of caveolae structure. In this
      review, we will give an introduction of organic anion transporters and its
      regulatory mechanisms. 

PMID- 24459482
TI  - Dysregulation of ENaC in Animal Models of Nephrotic Syndrome and Liver Cirrhosis.
AB  - Nephrotic syndrome and liver cirrhosis are common clinical manifestations, and
      are associated with avid sodium retention leading to the development of edema and
      ascites. However, the mechanism for the sodium retention is still incompletely
      understood and the molecular basis remains undefined. We examined the changes of
      sodium (co)transporters and epithelial sodium channels (ENaCs) in the kidneys of
      experimental nephrotic syndrome and liver cirrhosis. The results demonstrated
      that puromycin- or HgCl2-induced nephrotic syndrome was associated with 1) sodium
      retention, decreased urinary sodium excretion, development of ascites, and
      increased plasma aldosterone level; 2) increased apical targeting of ENaC
      subunits in connecting tubule and collecting duct segments; and 3) decreased
      protein abundance of type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2).
      Experimental liver cirrhosis was induced in rats by CCl4 treatment or common bile
      duct ligation. An increased apical targeting of alpha-, beta-, and gamma-ENaC
      subunits in connecting tubule, and cortical and medullary collecting duct
      segments in sodium retaining phase of liver cirhosis but not in escape phase of
      sodium retention. Immunolabeling intensity of 11betaHSD2 in the connecting tubule
      and cortical collecting duct was significantly reduced in sodium retaining phase
      of liver cirrhosis, and this was confirmed by immunoblotting. These observations
      therefore strongly support the view that the renal sodium retention associated
      with nephrotic syndrome and liver cirrhosis is caused by increased sodium
      reabsorption in the aldosterone sensitive distal nephron including the connecting
      tubule and collecting duct, and increased apical targeting of ENaC subunits plays
      a role in the development of sodium retention in nephrotic syndrome and liver
      cirrhosis. 

PMID- 24459484
TI  - Clinical usefulness of the serum anion gap.
AB  - The anion gap in the serum is useful in the interpretation of acid-base disorders
      and in the diagnosis of other conditions. In the early 1980s, ion-selective
      electrodes for specific ionic species were introduced for the measurement of
      serum electrolytes. This new method has caused a shift of the anion gap from 12+/
      4 mEq/L down 6+/-3 mEq/L. It is worthy for clinicians to understand the range of
      normal anion gap and the measuring methods for serum sodium and chloride in the
      laboratories that support their practice. While an increase in the anion gap is
      almost always caused by retained unmeasured anions, a decrease in the anion gap
      can be generated by multiple mechanisms. 

PMID- 24459483
TI  - Renal interstitial fibrosis and Angiotensin inhibition.
AB  - Tubulointerstitial (TI) fibrosis is a final common pathway to progressive renal
      injury of all forms of renal disease. However, once renal damage reaches a
      certain threshold, progression of renal disease is consistent, irreversible, and
      largely independent of the initial injury. Angiotensin (AT) II is the main
      effector of the renin angiotensin system (RAS) and effects that may contribute to
      the onset and progression of renal damage. AT II may also directly contribute to
      accelerate renal damage by sustaining cell growth, inflammation, and fibrosis.
      Interventions that inhibit the activity of the RAS are renoprotective and may
      retard or even halt the progression of chronic nephropathies. Unilateral ureteral
      obstruction suggested as a well-established experimental model of progressive
      interstitial expansion and fibrosis. Although technically challenging, some
      investigators have successfully relieved the obstruction and reported significant
      reduction in interstitial fibrosis severity. Drugs that modulate the RAS, such as
      ACE inhibitors and angiotensin type 1 (AT1) receptor antagonists, have
      demonstrated protective renal effects and can ameliorate fibrosis. However,
      neither ACE inhibitor nor AT1 receptor blockade completely suppresses progression
      of renal disease. Dual blockade of the RAS with ACE inhibitors and AT1 receptor
      blockers may provide renal benefit beyond therapy with either drug alone, due to
      their potential additive beneficial effect. 

PMID- 24459485
TI  - Pathogenesis and treatment of dyskalemia in maintenance hemodialysis and CAPD.
AB  - In end-stage renal disease (ESRD) patients regardless of dialysis modes, i.e.
      maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis
      (CAPD), potassium (K) homeostasis is regulated primarily via dialysis and
      extrarenal K regulation in the diverse daily K intake. However, K metabolism has
      been known to differ greatly between the two main methods of dialysis.
      Hyperkalemia is a common complication (10-24%) and the most common cause of the
      death (3-5%) among electrolyte disorders in patients on maintenance HD. On the
      contrary, hypokalemia (10-36%) is responsible for a rather common complication
      and independent prognostic factor on CAPD. Although excessive K intake or
      inadequate dialysis on maintenance HD and poor nutritional K intake on CAPD are
      accused without doubts upto 50% of ESRD patients as a primary cause of the K
      imbalance, i.e. hyperkalemia on HD and hypokalemia on CAPD, other contributory
      factors including certain medications and unknown causes remain still to be
      resolved. Accordingly, the effects of medications as another source of K
      imbalance on HD with RAS blockades and beta blockers as well as those of
      conventional and glucose-free dialysates (Icodextrin) for internal K
      redistribution on CAPD were evaluated with reviewing the literatures and our
      data. Furthermore, new developments in the clinical managements of hyperkalemia
      on HD following the exclusion of pseudohyperkalemia before the initiation of
      dialysis were suggested, especially, by the comparison of the effects between
      mono- and dual-therapy with medications for transcellular K shifting in the
      emergent situation. Also, the intraperitoneal K administration via conventional
      glucose-containing (2.5%) and glucose-free dialysates (Icodextrin) as a specific
      route of K-supplementation for hypokalemia on CAPD was examined for its
      efficiency and the degree of intracellular K shift between these two different
      types of dialysates. 

PMID- 24459487
TI  - The kidney knows the answers to the hidden messages in body water.

PMID- 24459486
TI  - D-lactic acidosis in humans: review of update.
AB  - D-Lactic acidosis has been well documented in ruminants. In humans, D-lactic
      acidosis is very rare, but D-lactic acidosis may be more common than generally
      believed and should be looked for in a case of metabolic acidosis in which the
      cause of acidosis is not apparent. The clinical presentation of D-lactic acidosis
      is characterized by episodes of encephalopathy and metabolic acidosis. The entity
      should be considered as a diagnosis in a patient who presents with metabolic
      acidosis accompanied by high anion gap, normal lactate level, negative Acetest,
      history of short bowel syndrome or malabsorption, and characteristic neurologic
      manifestations. Low carbohydrate diet, bicarbonate treatment, rehydration, and
      oral antibiotics would be helpful in controlling symptoms. 

PMID- 24459488
TI  - Mannitol-induced Metabolic Alkalosis.
AB  - Mannitol is an osmotic diuretic agent useful in a variety of clinical conditions.
      This study is based on acid-base and electrolyte changes seen after the
      intravenous infusion of hypertonic mannitol for the prevention of cerebral edema.
      The study subjects were divided into 3 groups: for group A, an amount of 300-900
      mL 15% mannitol was intravenously infused over the period of 60 to 90 minutes;
      for group B, 1,200-2,600 mL over 12 to 24 hours; and for group C, 3,200-4,900 mL
      over more than 24 hours. In group A, blood pH is increased from 7.43+/-0.07 to
      7.46+/-0.04, and plasma HCO3 (-) from 25.3+/-2.1 to 28.9+/-2.9 mEq/L, but plasma
      K(+) is decreased from 4.3+/-0.6 to 3.7+/-0.8 mEq/L. In group B, blood pH is
      increased from 7.42+/-0.02 to 7.47+/-0.06, and plasma HCO3 (-) from 25.2+/-1.8 to
      29.1+/-2.9 mEq/L, but plasma K(+) is decreased from 4.2+/-0.3 to 3.8+/-0.5 mEq/L.
      In group C, blood pH is increased from 7.41+/-0.01 to 7.52+/-0.04, and plasma
      HCO3 (-) from 24.9+/-1.2 to 27.7+/-2.5 mEq/L, but plasma K(+) is decreased from
      4.2+/-0.1 to 3.9+/-0.2 mEq/L. These results showed that intravenous infusion of
      mannitol could induce metabolic alkalosis and hypokalemia, regardless of its
      dose. The mannitol induced metabolic alkalosis may be due to increased renal HCO3
      (-) production. 

PMID- 24459489
TI  - Hypernatemia : successful treatment.
AB  - Hypernatremia reflects a net water loss or a hypertonic sodium gain, with
      inevitable hyperosmolality. Severe symptoms are usually evident only with acute
      and large increases in plasma sodium concentrations to above 158-160 mmol/l.
      Importantly, the sensation of intense thirst that protects against severe
      hypernatremia in health may be absent or reduced in patients with altered mental
      status or with hypothalamic lesions affecting their sense of thirst and in
      infants and elderly people. Non-specific symptoms such as anorexia, muscle
      weakness, restlessness, nausea, and vomiting tend to occur early. More serious
      signs follow, with altered mental status, lethargy, irritability, stupor, and
      coma. Acute brain shrinkage can induce vascular rupture, with cerebral bleeding
      and subarachnoid hemorrhage. However, in the vast majority of cases, the onset of
      hypertonicity is low enough to allow the brain to adapt and thereby to minimize
      cerebral dehydration. Organic osmolytes accumulated during the adaptation to
      hypernatremia are slow to leave the cell during rehydration. Therefore, if the
      hypernatremia is corrected too rapidly, cerebral edema results as the relatively
      more hypertonic ICF accumulates water. To be safe, the rate of correction should
      not exceed 12 mEq/liter/day. 

PMID- 24459490
TI  - Hyponatremia: management errors.
AB  - Rapid correction of hyponatremia is frequently associated with increased
      morbidity and mortality. Therefore, it is important to estimate the proper volume
      and type of infusate required to increase the serum sodium concentration
      predictably. The major common management errors during the treatment of
      hyponatremia are inadequate investigation, treatment with fluid restriction for
      diuretic-induced hyponatremia and treatment with fluid restriction plus
      intravenous isotonic saline simultaneously. We present two cases of management
      errors. One is about the problem of rapid correction of hyponatremia in a patient
      with sepsis and acute renal failure during continuous renal replacement therapy
      in the intensive care unit. The other is the case of hypothyroidism in which
      hyponatremia was aggravated by intravenous infusion of dextrose water and
      isotonic saline infusion was erroneously used to increase serum sodium
      concentration. 

PMID- 24459491
TI  - Pseudohyponatremia: does it matter in current clinical practice?
AB  - Serum consists of water (93% of serum volume) and nonaqueous components, mainly
      lipids and proteins (7% of serum volume). Sodium is restricted to serum water. In
      states of hyperproteinemia or hyperlipidemia, there is an increased mass of the
      nonaqueous components of serum and a concomitant decrease in the proportion of
      serum composed of water. Thus, pseudohyponatremia results because the flame
      photometry method measures sodium concentration in whole plasma. A sodium
      selective electrode gives the true, physiologically pertinent sodium
      concentration because it measures sodium activity in serum water. Whereas the
      serum sample is diluted in indirect potentiometry, the sample is not diluted in
      direct potentiometry. Because only direct reading gives an accurate
      concentration, we suspect that indirect potentiometry which many hospital
      laboratories are now using may mislead us to confusion in interpreting the serum
      sodium data. However, it seems that indirect potentiometry very rarely gives us
      discernibly low serum sodium levels in cases with hyperproteinemia and
      hyperlipidemia. As long as small margins of errors are kept in mind of clinicians
      when serum sodium is measured from the patients with hyperproteinemia or
      hyperlipidemia, the present methods for measuring sodium concentration in serum
      by indirect sodium-selective electrode potentiometry could be maintained in the
      clinical practice. 

PMID- 24459492
TI  - A case of primary aldosteronism with end stage renal disease.
AB  - A 52-year-old woman was referred to our hospital due to chronic renal failure
      with a 10-year history of hypertension. We found polycystic kidney disease,
      pulmonary tuberculosis and an aldosterone-producing adrenocortical mass. At this
      time, her serum potassium level and blood pressure were within the normal range.
      She refused hemodialysis and then was hospitalized because of uremic
      encephalopathy. On admission, her serum potassium level was normal without
      treatment and plasma aldosterone concentration highly elevated. She received
      hemodialysis, and thereafter hypokalemia developed. We then administered
      spironolactone, whereupon serum potassium level returned to the normal range. In
      this case, we thought that normokalemia was balanced hypokalemia of primary
      aldosteronism with hyperkalemia of chronic renal failure, and that hypokalemia
      developed after hemodialysis was due to an imbalanced primary aldosteronism with
      end stage renal disease. 

PMID- 24459493
TI  - Clinical Significance of Strong Ion Gap: between ICU and Hemodialysis Patients
      with Metabolic Acidosis.
AB  - Metabolic acidosis is the most frequent acid-base disorder in critically ill
      patients and dialysis patients. This study is to compare the conventional
      approach with the physicochemical approach between the intensive care unit (ICU)
      and hemodialysis (HD) patients. Fifty-seven ICU patients and 33 HD patients were
      enrolled. All data sets included simultaneous measurements of arterial blood gas
      with base deficit (BD), serum electrolytes, albumin, lactate, and calculated
      anion gap observed (AGobs). Physiochemical analysis was used to calculate the
      albumin and lactate-corrected anion gap (AGcorr), the base deficit corrected for
      unmeasured anions (BDua), the strong ion difference apparent (SIDa), the strong
      ion difference effective (SIDe), and the strong ion gap (SIG). The SIDa (37.5+/
      5.3 vs 33.9+/-9.0, p=0.045) and SIG (12.3+/-5.3 vs 8.6+/-8.8, p=0.043) was
      significantly higher in the HD group than the ICU group. SIG in the ICU group
      showed the highest correlation coefficient with AGobs, whereas SIG in the HD
      group with AGcorr. Concerning the contributions of the three main causes of
      metabolic acidosis, increased SIG was comparable between the ICU and HD group
      (n=48, 90.6% vs n=30, 93.8%), whereas hyperlactatemia (n=9, 17.0% vs n=0, 0%) and
      hyperchloremia (n=20, 35.1% vs n=2, 6.1%) was significantly increased in the ICU
      group compared with the HD group. Multiple underlying mechanisms are present in
      most of the ICU patients with metabolic acidosis compared with the HD patients.
      In conclusion, the physicochemical approach can elucidate the detailed mechanisms
      of metabolic acidosis in ICU and HD patients compared with conventional measures.

PMID- 24459494
TI  - Changes in Urine Osmolar Composition seen in Different Age Groups in the Local
      Korean Population.
AB  - Due to their unique living conditions and dietary habits, the Koreans' renal
      function model may be different from that of the Western people. About 40 years
      ago, a researcher reported that two thirds of the urine osmolality in Koreans was
      contributed by NaCl, while less than 1/3 by urea. It is known that the Koreans'
      daily consumption of NaCl is higher while their protein intake is lower, compared
      to that of the Westerners. Now-a-days, the Korean's dietary habit is changing to
      a westernized life style. In this study, we investigated whether there were
      changes in urine composition and osmolality according to age. The subject of
      study were 215 Koreans (128 male, 142 female, age 7-68 years) living in the
      Chonbuk and Chonnam province in Korea. We performed routine physical examinations
      and analyses of the urine Na(+), K(+), Cl(-), urea, NH3, creatinine, and
      osmolality on their 24 hour urine samples. In the case of the male, total body
      water, Na and Cl excretion, urine ammonia excretion were significantly changed
      between groups. In the case of the female, total body water and urine creatinine
      excretion were significantly changed between groups. We calculated the urine
      osmolar contribution of NaCl and urea. Our results showed that NaCl composed
      63.6% of total urine osmolality and Urea composed 36.4% of total urine
      osmolality. In conclusion, urine osmolar composition is similar to the 1960's,
      but further studies are required to elucidate the change of urine composition in
      this population for another 50 years. 

PMID- 24459495
TI  - Regulation of AQP2 in Collecting Duct : An emphasis on the Effects of Angiotensin
      II or Aldosterone.
AB  - Vasopressin, angiotensin II (AngII), and aldosterone are essential hormones in
      the regulation of body fluid homeostatsis. We examined the effects of AngII or
      aldosterone on the regulation of body water balance. We demonstrated that 1)
      short-term treatment with AngII in the primary cultured inner medullary
      collecting duct cells played a role in the regulation of AQP2 targeting to the
      plasma membrane through AT1 receptor activation. This potentiated the effects of
      dDAVP on cAMP accumulation, AQP2 phosphorylation, and AQP2 plasma membrane
      targeting; 2) pharmacological blockade of the AngII AT1 receptor in rats co
      treated with dDAVP and dietary NaCl-restriction (to induce high plasma endogenous
      AngII) resulted in an increase in urine production, a decrease in urine
      osmolality, and blunted the dDAVP-induced upregulation of AQP2; 3) long-term
      aldosterone infusion in normal rats or in rats with diabetes insipidus was
      associated with polyuria and decreased urine concentration, accompanied by
      decreased apical but increased basolateral AQP2 labeling intensity in the
      connecting tubule and cortical collecting duct; and 4) in contrast to the effects
      of dDAVP and AngII, short-term aldosterone treatment does not alter the
      intracellular distribution of AQP2. In conclusion, angiotensin II, and
      aldosterone could play a role in the regulation of renal water reabsorption by
      changing intracellular AQP2 targeting and/or AQP2 abundance, in addition to the
      vasopressin. 

PMID- 24459496
TI  - Effects of antioxidant drugs in rats with acute renal injury.
AB  - Acute renal failure is mainly caused by ischemia/reperfusion (I/R) injury or
      nephrotoxic drugs, in which reactive oxygen species (ROS) may play an important
      role. Therefore, antioxidants are expected to decrease the vulnerability of renal
      injury associated with oxidative challenges. alpha-Lipoic acid (alpha-LA), potent
      antioxidant, could act as ROS scavengers, iron chelators and enzyme modulators.
      In rats with acute renal injury, dysregulation of aquaporin (AQP) water channels
      and sodium transporters has been noted. I/R injury or cisplatin induced marked
      down-regulation of AQP1, AQP2 and AQP3 water channels, and type-3 Na-H exchanger,
      Na,K-ATPase, and Na-K-2Cl cotransporters, in association with impairment of
      urinary concentration and tubular sodium reabsorption. Treatment with alpha-LA
      prevented the dysregulation of AQP channels and sodium transporters, along with
      improved urinary concentrating capability and renal sodium reabsorption. 

PMID- 24459497
TI  - Regulation of Urea Transporters by Tonicity-responsive Enhancer Binding Protein.
AB  - Urea accumulation in the renal inner medulla plays a key role in the maintenance
      of maximal urinary concentrating ability. Urea transport in the kidney is
      mediated by transporter proteins that include renal urea transporter (UT-A) and
      erythrocyte urea transporter (UT-B). UT-A1 and UT-A2 are produced from the same
      gene. There is an active tonicity-responsive enhancer (TonE) in the promoter of
      UT-A1, and the UT-A1 promoter is stimulated by hypertonicity via tonicity
      responsive enhancer binding protein (TonEBP). The downregulation of UT-A2 raises
      the possibility that TonEBP also regulates its promoter. There is some evidence
      that TonEBP regulates expression of UT-A in vivo; (1) during the renal
      development of the urinary concentrating ability, expression of TonEBP precedes
      that of UT-A1; (2) in transgenic mice expressing a dominant negative form of
      TonEBP, expression of UT-A1 and UT-A2 is severely impaired; (3) in treatment with
      cyclosporine A, TonEBP was significantly downregulated after 28 days. This
      downregulation involves mRNA levels of UT-A2; (4) in hypokalemic animals,
      downregulation of TonEBP contributed to the down regulation of UT-A in the inner
      medulla. These data support that TonEBP directly contributes to the urinary
      concentration and renal urea recycling by the regulation of urea transporters. 

PMID- 24459498
TI  - Hypertensive hypokalemic disorders.
AB  - Hypokalemia is a common clinical problem. The kidney is responsible for long term
      potassium homoeostasis, as well as the serum potassium concentration. The main
      nephron site where K secretion is regulated is the cortical collecting duct,
      mainly via the effects of aldosterone. Aldosterone interacts with the
      mineralocorticoid receptor to increase sodium reabsorption and potassium
      secretion; the removal of cationic sodium makes the lumen relatively
      electronegative, thereby promoting passive potassium secretion from the tubular
      cell into the lumen through apical potassium channels. As a result, any condition
      that decreases the activity of renal potassium channels results in hyperkalemia
      (for example, amiloride intake or aldosterone deficiency) whereas their increased
      activity results in hypokalemia (for example, primary aldosteronism or Liddle's
      syndrome). The cause of hypokalemia can usually be determined from the history.
      If there is no apparent cause, the initial step is to see if hypokalemia is in
      associated with systemic hypertension or not. In the former group hypokalaemia is
      associated with a high mineralocorticoid effect or hyperactive sodium channel as
      in Liddle's syndrome. In hypertensive hypokalemic patients, measurement of the
      renin, aldosterone, and cortisol concentrations would be of help in differential
      diagnosis. 

PMID- 24459499
TI  - Metabolic acidosis in maintenance hemodialysis patients: clinical impact and
      intervention.
AB  - Metabolic acidosis has been considered as one of the reverse epidemiologic
      factors for the morbidity and mortality in maintenance hemodialysis patients
      (MHP). Expectedly, in the recent large scale epidemiologic study (The Dialysis
      Outcome Practice Pattern Study, DOPPS), a mild to moderate degree of predialysis
      metabolic acidosis has shown better nutritional status and lower relative risk
      for mortality and hospitalization in MHP. Similarly, another recent study of the
      largest sample size of MHP of more than 55,000 revealed the lowest unadjusted
      mortality with mild to moderate degree of predialysis HCO3 levels (17 to 23
      mEq/L). However, it was reversed after case-mix and multivariate adjustment,
      including the malnutrition-inflammation complex syndrome, so that predialysis
      HCO3 levels of more than 22 mEq/L had a lower death risk. On view of this up-to
      date on-going controversy about the optimal acid-base status for MHP, this paper
      will review the historical and break-through data about the pros and cons of
      metabolic acidosis published in the clinical human studies of MHP, a special
      subgroup of chronic kidney disease patients. Based on these results, if possible,
      we would like to suggest the best practice guideline, particularly, for the
      optimal predialysis HCO3 level, dialysate HCO3 concentration, and dietary protein
      intake. 

PMID- 24459500
TI  - SIADH associated with prostate cancer.
AB  - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most
      common disease leading to hyponatremia, and it is characterized by an
      inappropriately elevated serum ADH level relative to serum osmolality. This
      syndrome may occur in a variety of clinical settings including malignancies.
      However, it is rarely observed in association with prostate cancer. Moreover, its
      pathogenesis and clinical characteristics have not been completely understood. We
      report a case of SIADH associated with prostate cancer in a 64-year-old male
      patient with a literature review. 

PMID- 24459501
TI  - Water intoxication following low-dose intravenous cyclophosphamide.
AB  - Cyclophosphamide is frequently used for the treatment of severe lupus nephritis,
      but is very rarely associated with dilutional hyponatremia. Recently we
      experienced a case of water intoxication following low-dose intravenous
      cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide
      750 mg, the patient developed nausea, vomiting, and general weakness. Serum
      sodium concentration revealed 114 mEq/L and her hyponatremia was initially
      treated with hypertonic saline infusion. Then her serum sodium concentration
      rapidly recovered to normal with water restriction alone. During the course of
      intravenous pulse cyclophosphamide therapy, one must be aware of the possibility
      of significant water retention. 

PMID- 24459502
TI  - Altered Regulation of type 3 Na(+)/H(+) exchanger, type 1 Na(+)/HCO3 (-)
      cotransporter, and Na(+),K(+)-ATPase in the Kidney of Rats with Experimental
      Rhabdomyolysis.
AB  - Metabolic acidosis was shown to correlate with deterioration of renal function in
      patients with rhabdomyolysis. The present study was aimed to investigate whether
      the changes of type 3 Na(+)/H(+) exchanger (NHE3), type 1 Na(+)/HCO3 (-)
      cotransporter (NBC1), and Na(+),K(+)-ATPase alpha1 subunit may play a role in the
      pathogenesis of metabolic acidosis in glycerol-induced experimental
      rhabdomyolysis. Male Sprague-Dawley rats were deprived of fluid intake for 24
      hours, and then were injected with 50% glycerol in normal saline (10 mL/kg,
      intramuscularly). At 24 hours after the glycerol injection, rats were sacrificed
      by decapitation. Control rats were injected with normal saline. The protein
      expression of NHE3, NBC1 and Na(+),K(+)-ATPase alpha1 subunit was determined in
      the cortex of the kidney by immunoblotting and immunohistochemistry. Following
      the treatment of glycerol, creatinine clearance was significantly decreased, and
      high anion gap metabolic acidosis developed. In the experimental group, the
      expression of Na(+),K(+)-ATPase alpha1 subunit was significantly decreased in the
      cortex of the kidney. On the contrary, the expression of NHE3 and NBC1 was
      significantly increased. Immunohistochemical analyses confirmed the
      immunoblotting data. In conclusion, the coordinate up-regulation of NHE3 and NBC1
      may play an adaptive role against the metabolic acidosis in glycerol-induced
      rhabdomyolysis. 

PMID- 24459503
TI  - Effects of Increased Uric Acid Intake on the Abundance of Urate-anion exchanger
      and Organic Anion Transporter Proteins in the Rat Kidney.
AB  - Renal handling of uric acid mainly occurs in the proximal tubule, and
      bidirectional transport of urate may involve apical absorption via the urate
      anion exchanger (URAT1) and basolateral uptake via organic anion transporters
      (OAT1 and OAT3). In rat kidneys, we investigated whether the protein abundance of
      URAT1, OAT1, and OAT3 is affected by the increase in uric acid intake. Male
      Sprague-Dawley rats were randomly divided into control and uric acid-supplemented
      groups, and uric acid-supplemented rats were given 0.75 g of uric acid per 180 g
      body weight per day for 8 days. After the animal experiment, kidneys were
      harvested and semi-quantitative immunoblotting was carried out from cortical
      homogenates using polyclonal peptide-derived antibodies to URAT1, OAT1, and OAT3.
      Serum uric acid level showed an increasing tendency in the uric acid-supplemented
      rats compared with control rats, whereas urinary uric acid excretion was not
      significantly different between the uric acid-supplemented rats and control rats.
      URAT1 protein abundance in cortical homogenates was not significantly different
      between the uric acid-supplemented rats and control rats. However, OAT1 protein
      abundance was significantly increased in the uric acid-supplemented rats compared
      with the control rats. OAT3 protein abundance was not significantly different
      between the uric acid-supplemented rats and control rats. In conclusion, OAT1 may
      have a regulatory role in response to the increase in uric acid intake in the rat
      kidney. The up-regulation of OAT1 would exert stimulation of urinary uric acid
      excretion and might contribute to protection from hyperuricemia. 

PMID- 24459504
TI  - Dysregulation of Renal Cyclooxygenase-2 in Rats with Lithium-induced Nephrogenic
      Diabetes Insipidus.
AB  - This study aimed to examine whether the expression of major prostaglandin E2
      (PGE2) synthesis enzyme, cyclooxygenase-2 (COX-2), is changed in the kidneys of
      the rats with lithium-induced nephrogenic diabetes insipidus (Li-NDI). Sprague
      Dawley rats treated with lithium for 4 weeks were used as the NDI model and
      expression of renal COX-2 was determined by immunoblotting and
      immunohistochemistry. In Li-NDI where urine output was markedly increased and
      urine osmolality was significantly decreased, COX-2 expression in the inner
      medulla was decreased (28% of control), while it increased 18-fold in the cortex
      and outer medulla. Consistent with this, labeling intensity of COX-2 in macula
      densa region was increased, whereas it was decreased in the interstitial cells in
      the inner medulla, indicating a differential regulation of COX-2 between the
      cortex and inner medulla in Li-NDI. Accordingly, urinary PGE2 excretion was
      significantly increased in Li-NDI. In conclusion, there is a differential
      regulation of COX-2 between cortex and inner medulla in Li-NDI and urinary PGE2
      excretion is increased in Li-NDI, possibly due to an increased renal production.
      This may suggest that increased renal production of PGE2 could play a role in
      modulating water reabsorption in the renal collecting duct in Li-NDI. 

PMID- 24459505
TI  - Immunolocalization of Protein Kinase C Isoenzymes alpha, betaI, betaII and gamma
      in Adult and Developing Rat Kidney.
AB  - Protein kinase C (PKC) plays an important role not only in signal transduction
      mechanisms in various biological processes, but also in the regulation of growth
      and differentiation during development. We studied the classical PKCalpha, betaI,
      betaII and gamma, with regard to their expression in adult and developing rat
      kidney. PKCalpha appeared in the ureteric bud at embryonic day (E) 16, and the
      proximal and distal anlage at E18. After birth, the immunoreactivity of PKCalpha
      gradually decreased. In adult, PKCalpha was expressed intensely in the connecting
      tubule (CNT), the collecting ducts (CD) and the renal corpuscle, and weakly in
      the proximal and distal tubules. PKCbetaI appeared in the ureteric bud at E16,
      and the proximal anlage at E18. After birth, the immunoreactivity of PKCbetaI
      gradually disappeared from the CD and proximal tubule. In adult, PKCbetaI was
      expressed in the intercalated cells of the CNT and cortical CD, the proximal
      straight tubule, and the renal corpuscle. PKCbetaII appeared in distal anlage at
      E18, and increased markedly after birth. In the CD, PKCbetaII immunoreactivity
      appeared after birth. In adult, PKCbetaII was expressed in the distal tubule, the
      CNT and the CD. The immunoreactivity for PKCgamma appeared only in the proximal
      anlage at E18, and increased temporally around the time of birth. However, no
      immunoreactivity for PKCgamma was observed in adult rat kidney. These results
      indicate that classical PKC isoforms appear to play a role in the regulation of
      various renal functions and differentiation within specific functional units of
      the uriniferous tubule in rat kidney. 

PMID- 24459506
TI  - Altered Regulation of Type II 11beta-hydroxysteroid Dehydrogenase in the Kidney
      of Rats with Experimental Hypertension.
AB  - The present study was aimed at investigating the role of type II 11beta
      hydroxysteroid dehydrogenase (IIbeta-HSD II) in the development of hypertension.
      Two-kidney, one-clip (2K1C), deoxycorticosterone acetate (DOCA)/salt, or N (G)
      nitro-L-arginine methyl ester (L-NAME) hypertension was induced in male Sprague
      Dawley rats. Four weeks later, the expression of 11beta-HSD II mRNA was
      determined in the kidney by Northern blot analysis. The plasma level of
      aldosterone was measured by radioimmunoassay. In 2K1C hypertension, the
      expression of 11beta-HSD II was decreased in the clipped kidney and increased in
      the non-clipped kidney. The expression was increased in the remnant kidney of
      DOCA/salt hypertension, while decreased in the kidneys of L-NAME hypertension.
      The plasma level of aldosterone was increased, decreased, and remained unchanged
      in 2K1C, DOCA/salt, and L-NAME hypertension, respectively. The down-regulation of
      11beta-HSD II may contribute to the sodium retention, thereby increasing the
      blood pressure in 2K1C and L-NAME hypertension. On the contrary, the up
      regulation in DOCA/salt hypertension may play a compensatory role to dissipate
      the sodium retention. 

PMID- 24459507
TI  - Varying Dialysate Bicarbonate Concentrations in Maintenance Hemodialysis Patients
      Affect Post-dialysis Alkalosis but not Pre-dialysis Acidosis.
AB  - This study aimed to assess the effects of different dialysate bicarbonate
      concentrations in correcting acid-base imbalance in 53 stable hemodialysis
      patients in a university-hemodialysis unit. Three different bicarbonate
      concentrations were assigned, i.e. 25 mEq/L in 10, 30 mEq/L in 30, and 35 mEq/L
      in 13 patients. Blood gas analyses from arterial line blood samples before and
      after dialysis in the mid-week were performed for the determination of pH and
      serum bicarbonate (HCO3 (-)) concentration. The mean values of predialysis
      arterial HCO3 (-) were mildly acidotic in all 3 groups, but not significantly
      different among them, whereas those of post-dialysis arterial HCO3 (-) were
      alkalotic, especially in the group of 35 mEq/L as compared with the other two
      groups. The mean blood pH was not significantly different among the 3 groups. As
      expected, there was a positive correlation between pre-dialysis pH and post
      dialysis pH (r=0.45, p=0.001), and pre-dialysis HCO3 (-) and post-dialysis HCO3 (
      ) (r=0.58, p=0.000), but with a negative correlation between pre-dialysis HCO3 (
      ) and the increment of intradialytic HCO3 (-) following hemodialysis (r=-0.46,
      p=0.001). In conclusion, this study shows that the impact of conventional
      dialysate bicarbonate concentrations ranging from 25 to 35 mEq/L is not quite
      different on the mild degree of predialysis acidemia, but the degree of
      postdialysis alkalemia is more prominent in higher bicarbonate concentrations.
      Base supply by hemodialysis alone does not seem to be the main factor to
      determine the predialysis acidosis in end-stage renal disease patients on chronic
      maintenance hemodialysis. 

PMID- 24459508
TI  - Factors associated with Hypokalemia in Continuous Ambulatory Peritoneal Dialysis
      Patients.
AB  - Hypokalemia is a frequent problem in patients on continuous ambulatory peritoneal
      dialysis (CAPD) and is affected by multiple factors. To evaluate factors
      associated with hypokalemia, we studied 68 patients on maintenance CAPD treatment
      for at least six months. In univariate analysis, patients with hypokalemia were
      associated with older age and the presence of diabetes mellitus. Serum albumin,
      calcium-phosphate product, triglyceride, body mass index, protein nitrogen
      appearance, and lean body mass assessed by creatinine kinetics were significantly
      lower as compared to those without hypokalemia. Serum C-reactive protein was
      significantly higher in the patients with hypokalemia. Multivariate stepwise
      linear regression analysis revealed that the serum albumin level and the
      ultrafiltration volume at the peritoneal equilibration test were independent
      factors associated with hypokalemia. This suggests that the serum potassium level
      may be an important nutritional marker in CAPD patients. Further longitudinal
      investigation is needed to clarify this relationship. 

PMID- 24459509
TI  - Antimicrobial-induced Electrolyte and Acid-Base Disturbances.
AB  - Antimicrobials are one of the most widely prescribed classes of therapeutic
      agents. Although adverse effects of antimicrobials are generally minimal and
      reversible, serious sequelae can sometimes remain, such as unusual forms of renal
      failure, acid base disturbance and electrolyte abnormalities. Many
      antimicrobials, especially vancomycin or aminoglycosides, are associated with
      development of acute renal failure caused by acute tubular necrosis, allergic
      acute interstitial nephritis, or vasculitis. Besides, some antimicrobial agents
      can cause serious fluid and electrolyte imbalance. To prevent these serious
      consequences, early recognition and correction of their harmful renal and
      electrolyte effects are required. 

PMID- 24459510
TI  - Electrolyte and Acid-base disturbances associated with non-steroidal anti
      inflammatory drugs.
AB  - Inhibition of renal prostaglandin synthesis by non-steroidal anti-inflammatory
      drugs (NSAIDs) causes various electrolyte and acid-base disturbances including
      sodium retention (edema, hypertension), hyponatremia, hyperkalemia, and decreased
      renal function. Decreased sodium excretion can result in weight gain, peripheral
      edema, attenuation of the effects of antihypertensive agents, and rarely
      aggravation of congestive heart failure. Although rare, NSAIDs can cause
      hyponatremia by reducing renal free water clearance. Hyperkalemia could occur to
      a degree sufficient to cause cardiac arrhythmias. Renal function can decline
      sufficiently enough to cause acute renal failure. NSAIDs associated electrolyte
      and acid-base disturbances are not uncommon in some clinical situations. Adverse
      renal effects of NSAIDs are generally associated with prostaglandin dependent
      states such as volume-contracted states, low cardiac output, or other conditions
      that tend to compromise renal perfusion. All NSAIDs seem to share these adverse
      effects. In view of many NSAIDs users' susceptibility to renal adverse effects
      due to their underlying disease or condition, physicians should be cautious in
      prescribing NSAIDs to susceptible patients. 

PMID- 24459511
TI  - Electrolyte and Acid-base disturbances induced by clacineurin inhibitors.
AB  - Nephrotoxicity is the most common and clinically significant adverse effect of
      calcineurin inhibitors. Cyclosporine and tacrolimus nephrotoxicity is manifested
      by both acute azotemia and chronic progressive renal disease and tubular
      zdysfunction. An elevation in the plasma potassium concentration due to reduced
      efficiency of urinary potassium excretion is common in cyclosporine-treated
      patients; it may be severe and potentially life-threatening with concurrent
      administration of an angiotensin converting enzyme inhibitor, which diminishes
      aldosterone release. Tubular injury induced by cyclosporine can also impair acid
      excretion. This may be presented as a hyperchloremic metabolic acidosis
      associated with decreased aldosterone activity and suppression of ammonium
      excretion by hyperkalemia. Some patients treated with cyclosporine develop
      hypophosphatemia due to urinary phosphate wasting. Renal magnesium wasting is
      also common presumably due to drug effects on magnesium reabsorption.
      Hypomagnesemia has also been implicated as a contributor to the nephrotoxicity
      associated with cyclosporine. Both cyclosporine and tacrolimus are associated
      with hypercalciuria. Attention must be paid to drug dose, side effects, and drug
      interactions to minimize toxicity and maximize efficacy. 

PMID- 24459512
TI  - Pseudohyperphosphatemia in a patient with multiple myeloma.
AB  - Hyperphosphatemia is an unusual manifestation in patients with multiple myeloma
      without a significantly reduced glomerular filtration rate. Serum phosphate may
      be falsely elevated when a large amount of paraproteins is present in the serum,
      because ultraviolet light absorbance is elevated with the phosphomolybdate
      ultraviolet assay, which is most commonly used for serum phosphate measurement.
      This pseudohyperphosphatemia can be confirmed by deproteinization of the serum of
      patients. We report a case of multiple myeloma presenting with spurious
      hyperphosphatemia revealing pseudohyperphosphatemia by deproteinization of serum
      using sulfosalicylic acid. 

PMID- 24459513
TI  - Renal subcapsular hematoma : a consequence of reperfusion injury of long standing
      renal artery stenosis.
AB  - Renal artery stenosis is a cause of secondary hypertension which can be cured by
      surgical or radiological intervention such as percutaneous transluminal renal
      artery stent placement. In this case we present a subcapsular hematoma of the
      kidney, a complication following percutaneous transluminal stent placement in the
      renal artery. Reperfusion injury to the kidney may be a possible mechanism of
      subcapsular hematoma of the kidney. Long standing severe renal artery stenosis
      and high pre- and post-procedure pressure gradient might contribute to the
      complication. 

PMID- 24459514
TI  - Long-term Follow up of Congenital Adrenal Hyperplasia Patients with Hyponatremia.
AB  - Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency is an
      autosomal recessive disease, which leads to cortisol and aldosterone deficiency
      and hyperandrogenism. Typical medical treatment includes oral glucocorticoid and
      mineralocorticoid administration to suppress adrenal androgens and to compensate
      for adrenal steroid deficiencies. However, some patients stopped taking medicine
      without the doctor's consent. Among these patients, four cases of CAH patients
      showing the presence of hyponatremia as an initial electrolyte disorder were
      found with adrenal adenoma. Hypersecretion of adrenocorticotrophic hormone and
      chronic poor compliance to therapy appears to be associated with the development
      of the adrenal tumor. Two cases were managed with adrenalectomy because of
      increasing adrenal tumor size and virilization. Whereas the other two cases did
      not increase in size and were observed without adrenalectomy. Therefore, it is
      important that patients with CAH maintain steroid medication to avoid the
      appearance of adrenal tumor. 

PMID- 24459515
TI  - Effects of rosiglitazone on heat shock protein and the endothelin system in
      deoxycorticosterone acetate-salt hypertensive rats.
AB  - The deoxycorticosterone acetate (DOCA)-salt rat is known as a model of volume
      dependent hypertension and characterized by increased cardiac endothelin-1 (ET-1)
      content. Recently, it has been reported that rosiglitazone (RGT), a peroxisome
      proliferator-activated subtype gamma receptor agonist, shows blood pressure
      lowering effect. We investigated whether DOCA-salt hypertension is associated
      with altered expression of heat shock proteins (HSP) and ET-1 in the heart,
      aorta, and kidney, and whether RGT changes HSP expression and ET-1 in association
      with its blood pressure lowering effect. Two weeks after the silastic DOCA (200
      mg/kg) strips implantation, DOCA-salt rats were randomly divided to receive
      control diet with or without RGT (10 mg/kg/day) for another 2 weeks. The mRNA
      expression of ET-1 was determined by real time polymerase chain reaction. The
      expression of HSP was determined by semiquantitative immunoblotting. In DOCA-salt
      rats, systolic blood pressure was markedly increased, while creatinine clearance
      decreased. RGT treatment attenuated high blood pressure and decreased creatinine
      clearance in DOCA-salt rats. The mRNA expression of ET-1 was increased in DOCA
      salt rats compared to controls, which was counteracted by RGT treatment. The
      protein expression of HSP70, HSP32, and HSP25 was increased in the kidney and
      heart in DOCA-salt rats, which was attenuated by RGT treatment in the kidney, but
      not in the heart. In conclusion, increased expression of ET-1 may play a role in
      the pathogenesis of hypertension in DOCA-salt rats, which was counteracted by the
      treatment of RGT. Up-regulation of HSP70, HSP32, and HSP25 in the kidney and
      heart may play a role in organ protection against a variety of stresses. 

PMID- 24459516
TI  - Altered expression of sodium transporters and water channels in the submandibular
      gland of rats treated with nitric oxide synthesis inhibitors.
AB  - A role of nitric oxide (NO) in the regulation of sodium transporters and water
      channels in the salivary gland was investigated. Male Sprague-Dawley rats were
      treated with N(G) -nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking
      water) for 1 week. The control group was supplied with normal tap water. The
      expression of Na(+),K(+)-ATPase, type 2 Na(+)/K(+)/2Cl(-) cotransporter (NKCC2),
      type 1 Na(+)/H(+) exchanger (NHE1), alpha-subunit of epithelial sodium
      transporter (ENaC), and aquaporin-5 (AQP5) and aquaporin-1 (AQP1) proteins were
      determined in the submandibular gland by Western blot analysis. Following the
      treatment with L-NAME, the expression of Na(+),K(+)-ATPase alpha1-subunit, NKCC2,
      NHE1, and ENaC alpha-subunit increased significantly. On the contrary, the
      expression of AQP5 was significantly decreased, while that of AQP1 was not
      significantly altered. These findings indicate that the sodium transporters and
      water channels may be under a tonic regulatory influence of NO in the salivary
      gland. 

PMID- 24459517
TI  - Relationship between Serum N-Terminal Pro-Brain Natriuretic Peptide Level and
      Left Ventricular Dysfunction and Extracellular Water in Continuous Ambulatory
      Peritoneal Dialysis Patients.
AB  - This study inquired the relationship between serum N-terminal pro-brain
      natriuretic peptide (NT-proBNP) levels and left ventricular (LV) dysfunction and
      extracellular water in continuous ambulatory peritoneal dialysis (CAPD) patients.
      We conducted a cross-sectional study of 30 CAPD patients. Each patient was
      admitted to the department of internal medicine, Chosun University Hospital
      between February and October, 2006. Echocardiography was performed using HDI
      5000, allowing M-mode, two-dimensional measurement. A multifrequency bioimpedance
      analyzer was used; extracellular water was calculated as a percentage of total
      body water and was understood as the index of volume load of CAPD patients. The
      mean age was 47+/-12 years. Underlying causes of renal failure were 14 with
      diabetes mellitus, 7 with hypertension, and 9 with chronic glomerulonephritis.
      The mean serum NT-proBNP level was 14236.56 (83-35,000) pg/mL. LV mass index and
      LV ejection fraction were 151.67+/-42.5 g/m(2) and 57.48+/-12.9%, respectively.
      The mean extracellular water was 35.97+/-1.04%. Serum NT-proBNP levels correlated
      positively with LV mass index (r=0.768, p=0.01) and extracellular water (r=0.866,
      p=0.01) and negatively with LV ejection fraction (r=-0.808, p=0.01). Serum NT
      proBNP levels significantly correlated with LV mass index, LV ejection fraction,
      and extracellular water. Therefore, serum NT-proBNP levels can be a clinical
      predictive marker for LV hypertrophy, LV dysfunction, and volume status in CAPD
      patients. 

PMID- 24459518
TI  - The role of angiopoietin-1 in kidney disease.
AB  - Injury to the renal microvasculature and inflammatory process may be major
      factors in the progression of renal disease, therefore, protection of the renal
      endothelial cell and regulation of inflammatory process may be an important
      therapeutic target of renal disease. Thus, we evaluated the protective effect of
      cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) in unilateral
      ureteral obstruction (UUO)-induced renal fibrosis, cyclosporine A (CsA)-induced
      renal injury, and the diabetic nephropathy model. In the UUO model, morphologic
      examination indicated less tubular injury and tubulointerstitial fibrosis in mice
      that received COMP-Ang1 compared to vehicle-treated mice. Interstitial type I
      collagen, myofibroblast accumulation, renal surface microvasculature and renal
      blood flow were higher after treatment with COMP-Ang1 compared to vehicle-treated
      mice. COMP-Ang1 treatment decreased monocyte/macrophage infiltration, tissue
      levels of transforming growth factor beta1, and Smad 2/3 phosphorylation and
      increased Smad 7 in the obstructed kidney. In CsA-induced renal injury,
      histologic examination showed significantly decreased CsA-induced tubular damage
      and tubulointerstitial fibrosis in COMP-Ang1 treated mice. COMP-Ang1
      administration also decreased increased macrophage infiltration, adhesion
      molecule expression, TGF-beta1, and Smad 2/3 levels in CsA-treated kidneys, while
      increasing Smad 7 levels. Laser-Doppler sonographic findings and endothelial
      factor VIII staining revealed that COMP-Ang1 had a preservative effect on
      peritubular vasculature. In the diabetic nephropathy model, COMP-Ang1 reduced
      albuminuria and decreased mesangial expansion, thickening of the glomerular
      basement membrane and podocyte foot process broadening and effacement. COMP-Ang1
      may delay the fibrotic changes in the kidney of diabetic db/db mice through its
      anti-inflammatory or metabolic effects. In conclusion, COMP-Ang1 may be an
      endothelium-specific and anti-inflammatory therapeutic modality in fibrotic renal
      disease. 

PMID- 24459519
TI  - Nitric oxide in the kidney : its physiological role and pathophysiological
      implications.
AB  - Nitric oxide has been implicated in many physiologic processes that influence
      both acute and long-term control of kidney function. Its net effect in the kidney
      is to promote natriuresis and diuresis, contributing to adaptation to variations
      of dietary salt intake and maintenance of normal blood pressure. A pretreatment
      with nitric oxide donors or L-arginine may prevent the ischemic acute renal
      injury. In chronic kidney diseases, the systolic blood pressure is correlated
      with the plasma level of asymmetric dimethylarginine, an endogenous inhibitor of
      nitric oxide synthase. A reduced production and biological action of nitric oxide
      is associated with an elevation of arterial pressure, and conversely, an
      exaggerated activity may represent a compensatory mechanism to mitigate the
      hypertension. 

PMID- 24459520
TI  - Renal effects of prostaglandins and cyclooxygenase-2 inhibitors.
AB  - Prostaglandins (PGs) with best-defined renal functions are PGE2 and prostacyclin
      (PGI2). These vasodilatory PGs increase renal blood flow and glomerular
      filtration rate under conditions associated with decreased actual or effective
      circulating volume, resulting in greater tubular flow and secretion of potassium.
      Under conditions of decreased renal perfusion, the production of renal PGs serves
      as an important compensatory mechanism. PGI2 (and possibly PGE2) increases
      potassium secretion mainly by stimulating secretion of renin and activating the
      renin-angiotensin system, which leads to increased secretion of aldosterone. In
      addition, PGE2 is involved in the regulation of sodium and water reabsorption and
      acts as a counterregulatory factor under conditions of increased sodium
      reabsorption. PGE2 decreases sodium reabsorption at the thick ascending limb of
      the loop of Henle probably via inhibition of the Na(+)-K(+)-2Cl(-) cotransporter
      type 2 (NKCC2). Cyclooxygenase inhibitors may enhance urinary concentrating
      ability in part through effects to upregulate NKCC2 in the thick ascending limb
      of Henle's loop and aquaporin-2 in the collecting duct. Thus, they may be useful
      to treat Bartter's syndrome and nephrogenic diabetes insipidus. 

PMID- 24459521
TI  - Renin-Angiotensin system - considerations for hypertension and kidney.
AB  - The kidneys play a fundamental role in the long-term control of arterial pressure
      by regulating sodium balance and extracellular fluid volume. The renin
      angiotensin system (RAS) is at the center of the regulation of hypertension and
      progressive renal injury. It has gradually become clear that not only systemic
      RAS, but also intrarenal RAS has specific effects in the pathogenesis and
      progression of hypertension and renal damage. All of the RAS components are
      exhibited in the kidney and intrarenal angiotensin II (Ang II) is formed by
      multiple mechanisms. The demonstration of much enhanced levels of Ang II within
      specific renal compartments points out selective local regulation of Ang II in
      the kidney, showing that intrarenal Ang II levels are regulated in a way
      different from circulating Ang II. The importance of the RAS in involving proper
      nephrogenesis is also well known, and suppression of the RAS during fetal
      development may play a key role in mediating the structural and physiological
      changes observed in models of fetal programming of hypertension. 

PMID- 24459522
TI  - Vasopressin and vasopressin receptor antagonists.
AB  - Vasopressin, a neurohypophyseal peptide hormone, is the endogenous agonist at
      V1a, V1b, and V2 receptors. The most important physiological function of
      vasopressin is the maintenance of water homeostasis through interaction with V2
      receptors in the kidney. Vasopressin binds to V2 receptor and increases the
      number of aquaporin-2 at the apical plasma membrane of collecting duct principal
      cells. That induces high water permeability across the membrane. Several non
      peptide vasopressin receptor antagonists have been developed and are being
      studied primarily for treating conditions characterized by hyponatremia and fluid
      overload. Further studies are needed to determine how they are best used in these
      situations. 

PMID- 24459523
TI  - Recurrent Symptomatic Hyperglycemia on Maintenance Hemodialysis is not
      Necessarily Related to Hypertonicity : A Case Report.
AB  - On view of the absent or minimal osmotic diuresis in end stage renal disease,
      hyperglycemia on maintenance hemolysis as compared to nonketotic hyperosmolar
      status without underlying advanced renal failure has been noted to show a wide
      clinical spectrum form severe manifestations by hypertonicity to no clinical
      manifestations at all. We experienced a 60-year-old man with a known history of
      type 2 diabetes mellitus on maintenance hemodialysis for 2 years, who was
      admitted 4 times within 1 year with hyperglycemia (>500 mg/dL) accompanied by
      recurrent nausea and vomiting at each admission. However, the calculated
      effective osmolality (tonicity) in this case ranged only from 286 to 303 mOsm/kg
      H2O. During the past 6 months following meticulous education for the importance
      of compliance to medication, especially prokinetics for diabetic gastroparesis,
      he developed no further episode of hyperglycemia or nausea and vomiting. 

PMID- 24459524
TI  - Clinical factors associated with brachial-ankle pulse wave velocity in patients
      on maintenance hemodialysis.
AB  - Pulse wave velocity (PWV) is a main parameter for arterial stiffness. In patients
      with end-stage renal disease (ESRD), PWV is known to be associated with increased
      mortality. But factors related to the increased PWV in ESRD patients are not well
      defined. In addition, the carotid-femoral PWV (cfPWV) measurement, which
      traditionally has been used to evaluate arterial stiffness, has low
      reproducibility. Recently, brachial-ankle PWV (baPWV) measurement, which can be
      performed more easily than cfPWV measurement, has become available as a means of
      measuring PWV. The aim of this study is to investigate the clinical factors
      associated with increased baPWV in ESRD patients. BaPWV was examined for 65 ESRD
      patients on maintenance hemodialysis during the period between the 7(th) to the
      11(th) of February in 2005 using VP-1000. The clinical factors included age, sex,
      smoking history, blood pressure, diabetes, body mass index, interdialytic weight
      gain, duration of dialysis, lipid profile, uric acid, albumin, creatinine, C
      reactive protein, calcium, phosphate, intact parathyroid hormone, and hematocrit
      were analyzed regarding associations (or to determine associations) with baPWV.
      The median age was 53.8+/-12.0, 31 males and 34 females. BaPWV was 18.9+/-5.2 m/s
      and there was no significant difference between gender (18.1+/-4.4 m/s vs 19.4+/
      5.9 m/s, p=NS). In multiple regression models, age, predialysis systolic blood
      pressure, and diabetes were independent variables. In conclusion, age, systolic
      blood pressure, and diabetes were correlated with baPWV in ESRD patients. Thus
      baPWV measured by simple, noninvasive methods may become available for screening
      high risk groups in ESRD patients, although further longitudinal studies are
      necessary. 

PMID- 24459525
TI  - Kidney and calcium homeostasis.
AB  - Plasma calcium concentration is maintained within a narrow range (8.5-10.5 mg/dL)
      by the coordinated action of parathyroid hormone (PTH), 1,25(OH)2D3, calcitonin,
      and ionized calcium (iCa(2+)) itself. The kidney plays a key role in this process
      by the fine regulation of calcium excretion. More than 95% of filtered calcium is
      reabsorbed along the renal tubules. In the proximal tubules, 60% of filtered
      calcium is reabsorbed by passive mechanisms. In the thick ascending limb, 15% of
      calcium is reabsorbed by paracellular diffusion through paracellin-1 (claudin
      16). The calcium sensing receptor (CaSR) in the basolateral membrane of the thick
      ascending limb senses the change in iCa(2+) and inhibits calcium reabsorption
      independent to PTH and 1,25(OH)2D3. The fine regulation of calcium excretion
      occurs in the distal convoluted tubules and connecting tubules despite the fact
      that only 10-15% of filtered calcium is reabsorbed there. Transient receptor
      potential vanilloid 5 (TRPV5) and 6 (TRPV6) in the apical membrane act as the
      main portal of entry, calbindin-D28K delivers Ca(2+) in the cytoplasm, and then
      Na(2+)/Ca(2+) exchanger (NCX1) and plasma membrane Ca(2+)-ATPase in the
      basolateral membrane serve as an exit. In the cortical collecting duct, TRPV6 is
      expressed, but the role might be negligible. In addition to PTH and 1,25(OH)2D3,
      acid-base disturbance, diuretics, and estrogen affect on these calcium channels.
      Recently, klotho and fibroblast growth factor 23 (FGF23) are suggested as new
      players in the calcium metabolism. Klotho is exclusively expressed in the kidney
      and co-localized with TRPV5, NCX1, and calbindin-D28K. Klotho increases calcium
      reabsorption through trafficking of TRPV5 to the plasma membrane, and also
      converts FGF receptor to the specific FGF23 receptor. FGF23:klotho complex bound
      to FGF receptor inhibits 1alpha-hydroxylase of vitamin D, and contributes to
      calcium reabsorption and phosphate excretion in the kidney. 

PMID- 24459526
TI  - Kidney and phosphate metabolism.
AB  - The serum phosphorus level is maintained through a complex interplay between
      intestinal absorption, exchange intracellular and bone storage pools, and renal
      tubular reabsorption. The kidney plays a major role in regulation of phosphorus
      homeostasis by renal tubular reabsorption. Type IIa and type IIc Na(+)/Pi
      transporters are important renal Na(+)-dependent inorganic phosphate (Pi)
      transporters, which are expressed in the brush border membrane of proximal
      tubular cells. Both are regulated by dietary Pi intake, vitamin D, fibroblast
      growth factor 23 (FGF23) and parathyroid hormone. The expression of type IIa
      Na(+)/Pi transporter result from hypophosphatemia quickly. However, type IIc
      appears to act more slowly. Physiological and pathophysiological alteration in
      renal Pi reabsorption are related to altered brush border membrane
      expression/content of the type II Na(+)/Pi cotransporter. Many studies of genetic
      and acquired renal phosphate wasting disorders have led to the identification of
      novel genes. Two novel Pi regulating genes, PHEX and FGF23, play a role in the
      pathophysiology of genetic and acquired renal phosphate wasting disorders and
      studies are underway to define their mechanism on renal Pi regulation. In recent
      studies, sodium-hydrogen exchanger regulatory factor 1 (NHERF1) is reported as
      another new regulator for Pi reabsorption mechanism. 

PMID- 24459527
TI  - Magnesium metabolism.
AB  - Magnesium is the second most common intracellular divalent cation. Magnesium
      balance in the body is controlled by a dynamic interplay among intestinal
      absorption, exchange with bone, and renal excretion. Intestinal magnesium
      absorption proceeds in both a passive paracellular and an active transcellular
      manner. Regulation of serum magnesium concentrations is achieved mainly by
      control of renal magnesium reabsorption. Only 20% of filtered magnesium is
      reabsorbed in the proximal tubule, whereas 60% is reclaimed in the cortical thick
      ascending limb (TAL) and another 5-10% in the distal convoluted tubule (DCT). The
      passive paracellular transport of magnesium in the TAL is closely related with
      the mutations in claudin-16/paracellin-1 and is responsible for familial
      hypomagnesemia with hypercalciuria and nephrocalcinosis. The active transcellular
      transport of magnesium in the DCT was similarly enhanced by the realization that
      defects in transient receptor potential melastatin 6 (TRPM6) cause hypomagnesemia
      with secondary hypocalcemia. This channel regulates the apical entry of magnesium
      into epithelia and alters whole-body magnesium homeostasis by controlling urinary
      excretion. TRPM6 is regulated at the transcriptional level by acid-base status,
      17beta-estradiol, and both FK506 and cyclosporine. The molecular identity of the
      protein responsible for the basolateral exit of magnesium from the epithelial
      cell remains unidentified. 

PMID- 24459529
TI  - Effect of xiaoyaosan decoction on learning and memory deficit in rats induced by
      chronic immobilization stress.
AB  - Xiaoyaosan (XYS) decoction is a famous prescription which can protect nervous
      system from stress and treat liver stagnation and spleen deficiency syndrome
      (LSSDS). In this experiment, we observed the effect of XYS decoction on chronic
      immobilization stress (CIS) induced learning and memory deficit in rats from
      behaviors and changes of proteins in hippocampus. We used XYS decoction to treat
      CIS induced learning and memory deficit in rats with rolipram as positive
      control, used change of body weight and behavioral tests to determine whether the
      rats have LSSDS and have learning and memory deficit or not. We used Western
      blotting to determine the content of postsynaptic density protein 95 (PSD-95) and
      synaptophysin (SYP) in hippocampus. Results showed that XYS could improve the
      situation of slow weight gain induced by CIS, improve the ability of learning and
      memory, reverse the symptom of liver stagnation and spleen deficiency syndrome
      (LSSDS) in rats, and increase the levels of PSD-95 and SYP on the hippocampal
      nerve synapses. These findings suggested that XYS decoction may be helpful in
      reversing CIS induced learning and memory deficit by increasing the levels of PSD
      95 and SYP on the hippocampal nerve synapses and improving synaptic plasticity. 

PMID- 24459528
TI  - Effect of crataegus usage in cardiovascular disease prevention: an evidence-based
      approach.
AB  - Hawthorn (Crataegus oxyacantha) is a widely used Chinese herb for treatment of
      gastrointestinal ailments and heart problems and consumed as food. In North
      America, the role of treatment for heart problems dates back to 1800. Currently,
      evidence is accumulating from various in vivo and in vitro studies that hawthorn
      extracts exert a wide range of cardiovascular pharmacological properties,
      including antioxidant activity, positive inotropic effect, anti-inflammatory
      effect, anticardiac remodeling effect, antiplatelet aggregation effect,
      vasodilating effect, endothelial protective effect, reduction of smooth muscle
      cell migration and proliferation, protective effect against ischemia/reperfusion
      injury, antiarrhythmic effect, lipid-lowering effect and decrease of arterial
      blood pressure effect. On the other hand, reviews of placebo-controlled trials
      have reported both subjective and objective improvement in patients with mild
      forms of heart failure (NYHA I-III), hypertension, and hyperlipidemia. This paper
      discussed the underlying pharmacology mechanisms in potential cardioprotective
      effects and elucidated the clinical applications of Crataegus and its various
      extracts. 

PMID- 24459530
TI  - Antibacterial Chemical Constituent and Antiseptic Herbal Soap from Salvinia
      auriculata Aubl.
AB  - The bioassay-guided isolation of the active extract of Salvinia auriculata Aubl.
      led to the separation of three main compounds, characterized as stigmasterone,
      stigmasterol, and friedelinol. The pure form of diketosteroid presented a
      potential antibacterial activity with a minimum inhibitory concentration (MIC)
      value of 0.01 mg mL(-1) against Staphylococcus aureus isolated from animals with
      mastitis infections. The active extract also showed a similar result to that
      previously obtained with pure diketosteroid when tested with the same isolates.
      The present study's results demonstrate the potential of this plant as an
      excipient for the production of antibacterial soaps aimed at controlling bovine
      mastitis infections, especially on small farms. 

PMID- 24459531
TI  - Social and Cultural Factors Affecting Complementary and Alternative Medicine
      (CAM) Use during Menopause in Sydney and Bologna.
AB  - Background. Previous surveys found CAM use during menopause to be popular. This
      paper compares the results from two surveys (Sydney and Bologna) to examine
      factors that determine the extent and pattern of CAM use to alleviate menopausal
      symptoms. Methods. Women, aged 45-65 years, who were symptomatic when
      transitioning through menopause or asymptomatic but taking menopause-specific
      treatments, were recruited in Sydney (n=1,296) and Bologna (n=1,106) to complete
      the same voluntary, anonymous, and self-administered questionnaire. The results
      were reanalysed using stratified analyses to determine similarities and
      differences. Results. Demographics of the two cohorts differed significantly. CAM
      was more popular in Sydney. The most significant determinants of CAM use were the
      use of CAM for other conditions besides menopause and the severity of vasomotor
      symptoms. Occupational status was a determinant of CAM use amongst Bologna
      respondents only. In order to relieve symptoms, Australian and Italian women used
      different CAM modalities whose effectiveness was generally perceived as good.
      Conclusion. CAM use is popular amongst menopausal women from Sydney and Bologna.
      Differences in the patterns of CAM use seem to depend on CAM availability and on
      the educational level and professional status of users. The complex interaction
      between market, social, and cultural factors of CAM use seems to be more
      influential on women's choice of CAM than the available evidence of their
      effectiveness. 

PMID- 24459532
TI  - Antimutagenic Effect of Medicinal Plants Achillea millefolium and Bauhinia
      forficata In Vivo.
AB  - The investigation of traditionally used medicinal plants is valuable both as a
      source of potential chemotherapeutic drugs and as a measure of safety for the
      continued use of these medicinal plants. Achillea millefolium L. (AM) is an
      ancient remedial herb native to Europe that is used to treat wounds,
      gastrointestinal and hepatobiliary disorders, inflammation, headaches, and pain.
      Bauhinia forficata Link (BF), an Asiatic plant, is one of the most commonly used
      plants in folk medicine against diabetes. The aim of this study was to evaluate
      the cytotoxic and antimutagenic potential of aqueous extracts of AM and BF on
      bone marrow cells of Wistar rats treated in vivo. These plant extracts possess
      considerable antioxidant activity due to the presence of flavonoids and phenolic
      compounds. These compounds were determinants to noncytotoxic and
      antimutagenic/protective action of these plants, that reduced statistically the
      percentage of chromosomal alterations induced by the chemotherapeutic agent
      cyclophosphamide in simultaneous (AM, 68%; BF, 91%), pre- (AM, 68%; BF, 71%), and
      post-treatment (AM, 67%; BF, 95%). Therefore, the results of this study indicate
      that extracts of A. millefolium and B. forficata have antimutagenic potential and
      that their consumption can benefit the health of those using them as an
      alternative therapy. 

PMID- 24459534
TI  - Metabolic mapping of deep brain structures and associations with symptomatology
      in autism spectrum disorders.
AB  - Structural neuroimaging studies in autism report atypical volume in deep brain
      structures which are related to symptomatology. Little is known about metabolic
      changes in these regions, and how they vary with age and sex, and/or relate to
      clinical behaviors. Using magnetic resonance spectroscopy we measured N
      acetylaspartate, choline, creatine, myoinositol and glutamate in the caudate,
      putamen, and thalamus of 20 children with autism and 16 typically developing
      controls (7-18 years). Relative to controls, individuals with autism had elevated
      glutamate/creatine in the putamen. In addition, both groups showed age-related
      increases in glutamate in this region. Boys, relative to girls had increased
      choline/creatine in the thalamus. Lastly, there were correlations between
      glutamate, choline, and myoinositol in all three regions, and behavioral scores
      in the ASD group. These findings suggest changes in deep gray matter
      neurochemistry, which are sensitive to diagnosis, age and sex, and are associated
      with behavioral differences.

PMID- 24459533
TI  - Influence of acupuncture stimulation on cerebral network in functional diarrhea.
AB  - Acupuncture is a commonly used therapy for treating functional diarrhea (FD),
      although there is limited knowledge on the mechanism. The objectives of this
      study were to investigate the differences in brain activities elicited by
      acupuncture between FD patients and healthy controls (HC) so as to explore the
      possible mechanism. Eighteen FD patients and eighteen HC received 10 sessions of
      acupuncture treatment at ST25 acupoints. Functional magnetic resonance imaging
      (fMRI) scans were, respectively, performed before and after acupuncture. The
      defecation frequency, Bristol stool form scale (SBFS), and MOS 36-item Short
      Healthy Survey (SF-36) were employed to evaluate the clinical efficacy. After
      acupuncture, the FD patients showed a significant decrease in defecation
      frequency and BSFS score. The regional homogeneity (ReHo) map showed a decrease
      in the paracentral lobule and postcentral gyrus, and an increase in the angular
      gyrus, insula, anterior cingulate cortex (ACC), and precuneus in the FD group.
      Moreover, the changes in ReHo values in the ACC were correlated with the
      reduction in defecation frequency. Decreasing functional connectivity among the
      ACC, insula, thalamus, and orbital frontal cortex only existed in the FD group.
      Conclusively, acupuncture alleviated defecation frequency and improved stool
      formation in FD patients. The efficacy might result from the regulation of the
      homeostasis afferent processing network. 

PMID- 24459536
TI  - Annual risk of tuberculosis infection in hellenic air force recruits.
AB  - BACKGROUND: The annual risk of Tuberculosis infection (ARTI) is a key indicator
      in epidemiology, of the extent of transmission in a community. There have been
      several suggested methods in order to evaluate the prevalence of Tuberculosis
      infection using tuberculin skin data. This survey estimates the ARTI in young
      Hellenic air force recruits. The effect of BCG vaccination has also been
      investigated. MATERIALS AND METHODS: During the period November 2006-November
      2007 tuberculin skin tests were conducted to estimate the prevalence of
      mycobacterium tuberculosis infection and also to determine the ARTI. Tuberculin
      PPD-RT 23, dose 2 IU was used in 7.492 Greek air force military recruits with a
      mean age of 23.57 years. All recruits were examined for previous bacill Calmette
      Guerin vaccination through BCG scar. A vast number of personal, epidemiological
      significance, data of the participants was collected. RESULTS: The ARTI was 0.2%,
      in those who were not previously BCG vaccinated; this was derived from a
      tuberculin skin test cut-off point of 10 mm. There were not any statistically
      significant differences, neither between urban and rural population concerning
      the positivity of the tuberculin skin test, nor among the population in recent
      contact with immigrants from high-incidence countries. CONCLUSION: The estimated
      ARTI among non BCG vaccinated young Greek men is 0.2%.

PMID- 24459537
TI  - Adult Onset Still's Disease Presenting with Acute Respiratory Distress Syndrome:
      Case Report and Review of the Literature.
AB  - INTRODUCTION: Adult-onset Still's disease (AOSD) is a systemic inflammatory
      disorder characterized by rash, leukocytosis, fevers, and arthralgias. Pulmonary
      involvement has been reported rarely in AOSD, but acute respiratory distress
      syndrome (ARDS) is extremely rare and potentially fatal and must be recognized as
      potential manifestation of underlying AOSD. METHODS: We present a case of AOSD
      manifested by ARDS and review the previously reported cases in Medline/Pub med.
      RESULTS: Including this case, 19 cases of AOSD complicated with ARDS have been
      reported in the literature. CONCLUSIONS: It is important to recognize ARDS as a
      manifestation of AOSD so that proper diagnostic and therapeutic management can be
      initiated promptly.

PMID- 24459538
TI  - Visual Attention Modulates Insight Versus Analytic Solving of Verbal Problems.
AB  - Behavioral and neuroimaging findings indicate that distinct cognitive and neural
      processes underlie solving problems with sudden insight. Moreover, people with
      less focused attention sometimes perform better on tests of insight and creative
      problem solving. However, it remains unclear whether different states of
      attention, within individuals, influence the likelihood of solving problems with
      insight or with analysis. In this experiment, participants (N = 40) performed a
      baseline block of verbal problems, then performed one of two visual tasks, each
      emphasizing a distinct aspect of visual attention, followed by a second block of
      verbal problems to assess change in performance. After participants engaged in a
      center-focused flanker task requiring relatively focused visual attention, they
      reported solving more verbal problems with analytic processing. In contrast,
      after participants engaged in a rapid object identification task requiring
      attention to broad space and weak associations, they reported solving more verbal
      problems with insight. These results suggest that general attention mechanisms
      influence both visual attention task performance and verbal problem solving.

PMID- 24459539
TI  - Opioid overdose with gluteal compartment syndrome and acute peripheral
      neuropathy.
AB  - PATIENT: Male, 42 FINAL DIAGNOSIS: Gluteal compartment syndrome * acute
      peripheral nauropathy SYMPTOMS: - MEDICATION: - Clinical Procedure: - Specialty:
      Critical Care Medicine. OBJECTIVE: Management of emergency care. BACKGROUND:
      Heroin addiction is common, with an estimated 3.7 million Americans reporting to
      have used it at some point in their lives. Complications of opiate overdose
      include infection, rhabdomyolysis, respiratory depression and central or
      peripheral nervous system neurological complications. CONCLUSIONS: We present a
      42-year-old male admitted after heroin use with heroin-related peripheral nervous
      system complication preceded by an acute gluteal compartment syndrome and severe
      rhabdomyolysis. CASE REPORT: Early diagnosis and surgical intervention of the
      compartment syndrome can lead to full recovery while any delay in management can
      be devastating and can lead to permanent disability. The presence of peripheral
      nervous system injuries may portend a poor prognosis and can also lead to long
      term disability. Careful neurological evaluation for signs and symptoms of
      peripheral nervous system injuries is of paramount importance, as these may be
      absent at presentation in patients with opioid overdose. There is a potential
      risk of delaying a necessary treatment like fasciotomy in these patients by
      falsely attributing clinical symptoms to a preexisting neuropathy. Early EMG and
      nerve conduction studies should be considered when the etiology of underlying
      neurological weakness is unclear.

PMID- 24459540
TI  - Total hip replacement for an ochronotic patient: A technical trick.
AB  - PATIENT: Male, 46 FINAL DIAGNOSIS: Akkaptonuria Symptoms: Hip pain Medication: -
      Clinical Procedure: Total hip replacement Specialty: Orthopedics and
      Traumatology. OBJECTIVE: Unusual or unexpected effect of treatment. BACKGROUND:
      Ochronosis is an inherited metabolic disease in which there is an accumulation of
      excessive amounts of homogentisic acid in the connective tissue. As the disease
      progresses, the chronic inflammation in the damaged tissue can cause degeneration
      and osteoarthritis. There is no specific treatment for ochronosis because it is a
      rare disease and arthroplasty is seldom performed. CASE REPORT: We report the
      case of a 46-year-old male patient with ochronosis, who underwent an arthroplasty
      of the right hip due to osteoarthritis. The problems encountered during surgery
      are reported and discussed. CONCLUSIONS: Arthroplasty is a highly effective
      procedure for ochronotic patients. Particular attention to the surgical step is
      highly advised.

PMID- 24459541
TI  - Neurocysticercosis in a 23-year-old Chinese man.
AB  - PATIENT: Male, 23 FINAL DIAGNOSIS: Neurocysticerosis Symptoms: Diplopia * fever *
      headache * insomnia * neck stiffness * vomiting MEDICATION: Albendazole Clinical
      Procedure: - Specialty: Neurology. OBJECTIVE: Challenging differential diagnosis.
      BACKGROUND: Neurocysticercosis is a brain infection caused by the larval stage of
      the tapeworm Taenia (T.) solium. It is the most important parasitic disease of
      the human central nervous system and represents the most common cause of acquired
      epilepsy in developing countries. CASE REPORT: Here, we report the case of a 23
      year-old Chinese man who presented to the emergency department with a 7-day
      history of helmet headache radiating to the nuchal region and associated with
      vomiting, confusion, and fever. Cerebrospinal fluid (CSF) was clear, with
      increased pressure, lymphocytic pleocytosis, decreased glucose, and increased
      protein levels. Bacterial antigen detection test on CSF was negative, as were CSF
      bacterial and fungal cultures. Despite broad-spectrum antibiotic and antiviral
      therapy, the patient still complained of insomnia, diplopia, headache, neck
      stiffness, and pain in the sacral region. A second LP was performed and CSF had
      the same characteristics as the first LP. A brain and spinal cord MRI revealed
      widespread arachnoiditis and small septated cysts with CSF-like signal in the
      cisterna magna, within the fourth ventricle, and at the level of L3-L4.
      Cysticercus-specific immunoglobin G antibodies were detected by ELISA in the CSF.
      The patient received albendazole (15 mg/kg/day) and dexamethasone (5 mg/day) for
      4 weeks, with progressive resolution of neurological symptoms. CONCLUSIONS: This
      case shows that, even if rare, neurocysticercosis may be responsible for
      meningeal symptoms and should be included in the differential diagnosis,
      especially in patients from endemic countries.

PMID- 24459542
TI  - The Boston marathon tragedy.

PMID- 24459543
TI  - Concentric and eccentric: muscle contraction or exercise?

PMID- 24459544
TI  - Letter to the editor and response.

PMID- 24459545
TI  - Adductor pollicis longus strain in a professional baseball player: case report
      and review of thenar pain.
AB  - Thenar pain can represent a significant morbidity for a baseball player who
      relies on manual dexterity for gripping a bat and precise and accurate throws.
      While osseous, ligamentous, and neurovascular pathologies are commonly
      considered, musculotendinous injuries are often neglected in the differential
      diagnosis of thenar pain. We present a case of adductor pollicis longus strain as
      a cause of acute thenar pain in a baseball player. Adductor pollicis longus
      strains should be considered in any baseball player sustaining a hyperabduction
      force to the thumb. 

PMID- 24459546
TI  - Rehabilitation of low back pain in golfers: from diagnosis to return to sport.
AB  - CONTEXT: Low back injuries are the most common injury in golf. Best practice
      guidelines for rehabilitation and prevention of these injuries are helpful for
      health care professionals and all golfers. OBJECTIVE: To establish a best
      practice clinical model for low back pain in golfers from diagnosis through
      treatment and rehabilitation to return to golf. EVIDENCE ACQUISITION: The PubMed
      database and Google Scholar were searched from 1993 to 2012 with the following
      keywords: golf and low back injury, low back injury, golf and low back pain, golf
      injury prevention, golf modern swing, muscles in golf swing, low back
      rehabilitation, diaphragm, and core stability. All studies addressed in some
      manner the rehabilitation, prevention, or return to sport from low back injury,
      preferably in direct relation to golf, as well as muscle firing patterns used
      during the golf swing. RESULTS: Best practice for rehabilitation and prevention
      of low back injury in golf appears to be through a multidisciplinary approach.
      CONCLUSION: Movement patterns, muscle imbalances, and type of swing utilized all
      have a direct effect on the forces applied to the spine during the golf swing and
      need to be assessed to prevent or rehabilitate injury. Understanding the golf
      swing and how the body works during the swing is necessary.

PMID- 24459547
TI  - Neck strength imbalance correlates with increased head acceleration in soccer
      heading.
AB  - BACKGROUND: Soccer heading is using the head to directly contact the ball, often
      to advance the ball down the field or score. It is a skill fundamental to the
      game, yet it has come under scrutiny. Repeated subclinical effects of heading may
      compound over time, resulting in neurologic deficits. Greater head accelerations
      are linked to brain injury. Developing an understanding of how the neck muscles
      help stabilize and reduce head acceleration during impact may help prevent brain
      injury. HYPOTHESIS: Neck strength imbalance correlates to increasing head
      acceleration during impact while heading a soccer ball. STUDY DESIGN:
      Observational laboratory investigation. METHODS: Sixteen Division I and II
      collegiate soccer players headed a ball in a controlled indoor laboratory setting
      while player motions were recorded by a 14-camera Vicon MX motion capture system.
      Neck flexor and extensor strength of each player was measured using a spring-type
      clinical dynamometer. RESULTS: Players were served soccer balls by hand at a mean
      velocity of 4.29 m/s (+/-0.74 m/s). Players returned the ball to the server using
      a heading maneuver at a mean velocity of 5.48 m/s (+/-1.18 m/s). Mean neck
      strength difference was positively correlated with angular head acceleration (rho
      = 0.497; P = 0.05), with a trend toward significance for linear head acceleration
      (rho = 0.485; P = 0.057). CONCLUSION: This study suggests that symmetrical
      strength in neck flexors and extensors reduces head acceleration experienced
      during low-velocity heading in experienced collegiate players. CLINICAL
      RELEVANCE: Balanced neck strength may reduce head acceleration cumulative
      subclinical injury. Since neck strength is a measureable and amenable strength
      training intervention, this may represent a modifiable intrinsic risk factor for
      injury.

PMID- 24459549
TI  - Exercise-associated hyponatremia in an ultra-endurance mountain biker: a case
      report.
AB  - Symptomatic exercise-associated hyponatremia (EAH), which is relatively common
      among marathon runners, is an uncommon event among ultra-endurance athletes. A 44
      year-old man presented to the emergency department with increased thirst after
      successfully completing a 100-mile mountain bike race in Leadville, Colorado.
      Initial laboratory tests revealed a blood sodium level of 116 mEq/L. The primary
      etiologic factor in EAH is fluid consumption in excess of fluid losses in
      prolonged exertion. Early diagnosis and management is crucial to prevent cerebral
      and pulmonary edema. 

PMID- 24459548
TI  - The incidence of injury among male and female intercollegiate rugby players.
AB  - BACKGROUND: The National Collegiate Athletic Association classifies women's rugby
      as an emerging sport. Few studies have examined the injury rates in women's
      collegiate rugby or compared injury rates between sexes. HYPOTHESIS: Injury rates
      will differ between female and male intercollegiate club rugby players. STUDY
      DESIGN: Descriptive epidemiological study. METHODS: Five years of injury data
      were collected from the men's and women's rugby teams at a US service academy
      using the institution's injury surveillance system. The primary outcome of
      interest was the incidence rate of injury during the study period per 10,000
      athlete exposures. Incidence rate ratios (IRRs) were calculated using a Poisson
      distribution to compare the rates by sex. RESULTS: During the study period, the
      overall incidence rate for injury was 30% higher (IRR = 1.30, 95% CI: 1.09, 1.54)
      among men when compared with women; however, the distribution of injuries varied
      by sex. The incidence rate for ACL injury among women was 5.3 times (IRR = 5.32,
      95% CI: 1.33, 30.53) higher compared with that among men. Men were 2.5 times (IRR
      = 2.54, 95% CI: 1.03, 7.52) more likely to sustain a fracture. The rate of
      acromioclavicular joint injury was 2.2 times (IRR = 2.19, 95% CI: 1.03, 5.19)
      higher among men when compared with women. Men were 6.6 times (IRR = 6.55, 95%
      CI: 2.65, 20.91) more likely to have an open wound than women. CONCLUSION: There
      are differences in injury rates and patterns between female and male American
      rugby players. CLINICAL RELEVANCE: The differences in injury patterns may reflect
      distinct playing styles, which could be the result of the American football
      background common among many of the male players.

PMID- 24459550
TI  - Comparison of the effect of medical assistants versus certified athletic trainers
      on patient volumes and revenue generation in a sports medicine practice.
AB  - BACKGROUND: Research has shown increases in efficiency and productivity by using
      physician extenders (PEs) in medical practices. Certified athletic trainers
      (ATCs) that work as PEs in primary care sports medicine and orthopaedic practices
      improve clinic efficiency. HYPOTHESIS: When compared with a medical assistant
      (MA), the use of an ATC as a PE in a primary care sports medicine practice will
      result in an increase in patient volume, charges, and collections. STUDY DESIGN:
      Cross-sectional study. METHODS: For 12 months, patient encounters, charges, and
      collections were obtained for the practices of 2 primary care sports medicine
      physicians. Each physician was assisted by an ATC for 6 months and by an MA for 6
      months. Eighty full clinic days were examined for each physician. RESULTS:
      Statistically significant increases were found in all measured parameters for the
      ATC compared with the MA. Patient encounters increased 18% to 22% per day, and
      collections increased by 10% to 60% per day. CONCLUSION: ATCs can optimize
      orthopaedic sports medicine practice by increasing patient encounters, charges,
      and collections. CLINICAL RELEVANCE: Orthopaedic practices can be more efficient
      by using ATCs or MAs as PEs.

PMID- 24459551
TI  - Action in the event tent! Medical-legal issues facing the volunteer event
      physician.
AB  - CONTEXT: Physicians need to consider medical-legal issues when volunteering their
      time to assist with community mass-participation and athletic events. This
      article also reviews medical-legal aspects of the volunteer physician's out-of
      state practice. Seven cases illustrate the importance of expertise and planning
      to avoid legal issues for the volunteer event physician. EVIDENCE ACQUISITION:
      Relevant studies, expert opinion, medical-legal legislation, and medical-legal
      cases were reviewed. RESULTS: Physicians typically make 4 common assumptions
      regarding these types of events: Good Samaritan legislation, event liability
      insurance, personal liability insurance, and waivers. We discuss the intent of
      these assumptions and the reality of how, or how not, they provide any protection
      to the volunteer event physician. CONCLUSION: The intent of this article is to
      make physicians aware of medial-legal issues when volunteering their time for
      community and athletic events.

PMID- 24459552
TI  - Muscle injuries in athletes: enhancing recovery through scientific understanding
      and novel therapies.
AB  - CONTEXT: Muscle injuries are extremely common in athletes and often produce pain,
      dysfunction, and the inability to return to practice or competition. Appropriate
      diagnosis and management can optimize recovery and minimize time to return to
      play. EVIDENCE ACQUISITION: Contemporary papers, both basic science and clinical
      medicine, that investigate muscle healing were reviewed. A Medline/PubMed search
      inclusive of years 1948 to 2012 was performed. RESULTS: Diagnosis can usually be
      made according to history and physical examination for most injuries. Although
      data are limited, initial conservative management emphasizing the RICE principles
      and immobilization of the extremity for several days for higher grade injuries
      are typically all that is required. Injection of corticosteroids may clinically
      enhance function after an acute muscle strain. Additional adjunctive treatments
      (nonsteroidal anti-inflammatory drugs, platelet-rich plasma, and others) to
      enhance muscle healing and limit scar formation show promise but need additional
      data to better define their roles. CONCLUSION: Conservative treatment
      recommendations will typically lead to successful outcomes after a muscle injury.
      There is limited evidence to support most adjunctive treatments.

PMID- 24459553
TI  - Paget-schroetter syndrome: a review of effort thrombosis of the upper extremity
      from a sports medicine perspective.
AB  - Paget-Schroetter is a rare diagnosis in the general population; however, it is
      more common in younger, physically active individuals. Clinicians must be
      familiar with the symptoms, physical examination, and initial imaging and
      treatment to expedite care and prevent possible life-threatening complications.
      Urgent referral to a regional specialist may improve the opportunity for
      thrombolysis to restore blood flow through the subclavian vein and to decrease
      the chance of pulmonary embolus, recurrent thrombosis, or need for vein grafting,
      as well as to improve the time to return to full activity (athletics and/or
      manual labor). 

PMID- 24459554
TI  - A rare cause of foot pain with golf swing: symptomatic os vesalianum pedis-a case
      report.
AB  - The os vesalianum is an uncommon accessory bone of the foot, located proximally
      to the base of the fifth metatarsal. It is usually asymptomatic and detected
      incidentally on radiographs. This is a case of bilateral os vesalianum,
      symptomatic only in the right foot, in a golf player. After a failed nonoperative
      treatment, the os vesalianum in the symptomatic foot was excised and the peroneus
      brevis tendon reattached using a suture anchor. The functional outcome was
      excellent, and the patient returned to golf 8 weeks after surgery. 

PMID- 24459555
TI  - Development and validation of the elbow demand rating scale.
AB  - BACKGROUND: Overhead sports place the greatest strain on the elbow of any of the
      upper extremity joints. Unfortunately, athlete-specific functional outcome tools
      do not exist for the elbow. HYPOTHESES: THE ELBOW DEMAND RATING SCALE (EDS) WILL
      DEMONSTRATE STRONG RELIABILITY AND VALIDITY PROPERTIES: (1) test-retest
      reliability with a 2-week EDS administration, (2) internal reliability of the
      subscales, and (3) construct validity through lower scores for patients with
      elbow injuries. STUDY DESIGN: Prospective case-control study. METHODS: Patients
      with (n = 19) and without elbow injuries (n = 19) completed the EDS during their
      routine clinical appointment and 2 weeks later. Clinicians completed the
      functional portion of the EDS. RESULTS: The EDS demonstrated strong test-retest
      reliability and construct validity. Internal reliability was moderate (alpha =
      0.50). Exploratory analyses further supported construct validity using
      demographic survey questions regarding elbow pain and symptoms. CONCLUSION:
      Overall, the EDS demonstrated moderate to strong psychometric properties in a
      patient population with elbow injuries, and its use is supported for young
      athletes. CLINICAL RELEVANCE: The EDS provides clinicians working with adolescent
      and young adult athletes a scale to direct care and determine intervention
      success or failure.

PMID- 24459556
TI  - Suprascapular nerve entrapment due to a stenotic foramen: a variant of the
      suprascapular notch.
AB  - Suprascapular nerve (SSN) entrapment is an uncommon cause of posterior shoulder
      pain. Entrapment can be relieved arthroscopically in some cases. 

PMID- 24459558
TI  - The practical uses of ultrasound in a clinical setting to diagnose thrombosis of
      the ulnar artery.
AB  - A 43-year-old professional skateboarder presented to the sports medicine clinic
      with complaints of left wrist pain to the ulnar aspect. Two weeks prior to
      presentation, his wrist became suddenly painful with no specific trauma. He
      reported a history of falls over the years while skateboarding but none directly
      correlated to his onset of wrist pain. Radiographic results were negative for
      wrist or hand fracture. Physical examination yielded tenderness and mild swelling
      to the ulnar aspect of the wrist. Musculoskeletal ultrasound was used to assess
      tendon and ligament integrity, all of which was intact. Both radial and ulnar
      arteries were visualized, and ulnar artery thrombosis was incidentally diagnosed.
      He was advised to immediately proceed to the hospital, where an open arthrectomy
      was performed to the ulnar artery the following day. The patient was released
      from the hospital 2 days later and subsequently made a full recovery. 

PMID- 24459557
TI  - Return to sport following shoulder surgery in the elite pitcher: a systematic
      review.
AB  - CONTEXT: The ability to return to elite pitching, performance, and clinical
      outcomes of shoulder surgery in elite baseball pitchers are not definitively
      established. OBJECTIVE: To determine (1) the rate of return to sport (RTS) in
      elite pitchers following shoulder surgery, (2) postoperative clinical outcomes
      upon RTS, and (3) performance upon RTS and to compare RTS rates in different
      types of shoulder surgery. DATA SOURCES: Using Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist, Medline,
      SciVerse Scopus, SportDiscus, and Cochrane Central Register of Controlled Trials
      were searched. STUDY SELECTION: Levels I-IV evidence were eligible for inclusion
      if performance-based (eg, RTS) and/or clinical outcome-based reporting of
      outcomes were reported following surgical treatment of shoulder pathology in
      elite pitchers (major or minor league or collegiate). DATA EXTRACTION: Subject,
      shoulder, and pre- and postoperative performance-based variables of interest were
      extracted. All shoulder surgery types were potentially inclusive (eg, open,
      arthroscopic, rotator cuff, labrum, biceps, acromioclavicular joint, fracture).
      Study methodological quality was analyzed using the Modified Coleman Methodology
      Score (MCMS). RESULTS: Six studies were analyzed (287 elite male pitchers [mean
      age, 27 years] who underwent shoulder surgery, with 99% on the dominant, throwing
      shoulder). MCMS was 38 (poor). Most pitchers were professional, with a mean
      career length of 6.58 years and postoperative clinical follow-up of 3.62 years.
      In 5 of 6 studies, multiple diagnoses were addressed concomitantly at surgery.
      Rate of RTS was 68% at mean 12 months following surgery. Twenty-two percent of
      Major League Baseball (MLB) pitchers never RTS in MLB. Overall performance did
      improve following surgery; however, this did not improve to pre-injury levels.
      CONCLUSION: In this systematic review, the rate of return to elite baseball
      pitching following surgery was established. Performance tended to decrease prior
      to surgery and gradually improve postoperatively, though not reaching pre-injury
      levels of pitching. LEVEL OF EVIDENCE: IV (systematic review of studies level I
      IV evidence), therapeutic.

PMID- 24459560
TI  - COLLABORATIVE LABELING OF MALIGNANT GLIOMA.
AB  - Malignant gliomas represent an aggressive class of central nervous system
      neoplasms which are often treated by maximal surgical resection. Herein, we seek
      to improve the methods available to quantify the extent of tumors as seen on
      magnetic resonance imaging using Internet-based, collaborative labeling. In a
      study of clinically acquired images, we demonstrate that teams of minimally
      trained human raters are able to reliably characterize the gadolinium-enhancing
      core and edema tumor regions (Dice ~ 0.9). The collaborative approach is highly
      parallel and efficient in terms of time (the total time spent by the collective
      is equivalent to that of a single expert) and resources (only minimal training
      and no hardware is provided to the participants). Hence, collaborative labeling
      is a very promising new technique with potentially wide applicability to
      facilitate cost-effective manual labeling of medical imaging data.

PMID- 24459562
TI  - Ventricular torsion: research tool or novel clinical indicator?

PMID- 24459561
TI  - Current clinical application of intracardiac flow analysis using
      echocardiography.
AB  - In evaluating the cardiac function, it is important to have a comprehensive
      assessment of structural factors, such as the myocardial or valvular function and
      intracardiac flow dynamics that pass the heart. Vortex flow that form during left
      ventricular filling have specific geometry and anatomical location that are
      critical determinants of directed blood flow during ejection. The formation of
      abnormal vortices relates to the abnormal cardiac function. Therefore, vortex
      flow may offer a novel index of cardiac dysfunction. Intracardiac flow
      visualization using ultrasound technique has definite advantages with a higher
      temporal resolution and availability in real time clinical setting. Vector flow
      mapping based on color-Doppler and contrast echocardiography using particle image
      velocimetry is currently being used for visualizing the intracardiac flow. The
      purpose of this review is to provide readers with an update on the current method
      for analyzing intracardiac flow using echocardiography and its clinical
      applications. 

PMID- 24459563
TI  - Effect of mitral inflow pattern on diagnosis of severe mitral regurgitation in
      patients with chronic organic mitral regurgitation.
AB  - BACKGROUND: To determine sensitivity and specificity of E wave velocity in
      patients with severe chronic organic mitral regurgitation (MR) and normal left
      ventricular ejection fraction (EF) and to evaluate prevalence of A wave dominance
      in patients with severe MR. METHODS: We compared 35 patients with quantified
      severe, chronic, quantified, organic MR due to flail/prolapsed leaflets who had
      reparative surgery with 35 age-matched control subjects. EXCLUSION CRITERIA: EF <
      60%, atrial fibrillation, and more than mild aortic regurgitation. RESULTS: Mean
      [standard deviation (SD)] age [70 (8) years vs. 69 (8) years; p = 0.94] and mean
      (SD) EF [66% (6%) vs. 65% (4%); p = 0.43] were not different between the two
      groups. Mean (SD) E wave velocity was greater in case patients than control
      subjects [1.2 (0.3) m/sec vs. 0.7 (0.15) m/sec; p < 0.001]. However, E wave
      velocity of 1.2 m/sec had a sensitivity of only 57% [95% confidence interval
      (CI), 41-7 and a specificity of 100% (95% CI, 90-100%) in identifying severe MR.
      E wave velocity of 0.9 m/sec had a more optimal combined sensitivity (89%; 95%
      CI, 74-95%) and specificity (86%; 95% CI, 71-94%). A wave dominance was seen in
      18% of case patients and 66% of control subjects (p < 0.001). CONCLUSION: E wave
      velocity of 1.2 m/sec is specific not sensitive for severe organic MR; E wave
      velocity of 0.9 m/sec has better sensitivity and specificity. A wave dominance
      pattern alone cannot exclude patients with severe organic MR. Our findings
      highlight the importance of a comprehensive echocardiographic exam rather than
      relying on a few Doppler parameters in diagnosing MR.

PMID- 24459564
TI  - Left ventricular torsion changes post kidney transplantation.
AB  - BACKGROUND: To quantify changes of left ventricular (LV) torsion in patients' pre
      and post kidney transplantation. METHODS: A prospective study was conducted on 48
      patients who received kidney transplantation for end stage renal disease and
      without myocardial infarction. The rotation, twist and torsion of LV were studied
      pre and post kidney transplantation (6 months post transplantation) using
      velocity vector imaging by echocardiography. The data is expressed as mean +/-
      standard deviation and compared by paired t-test at the p < 0.05 significance
      level. RESULTS: Six months post kidney transplantation, left ventricular ejection
      fraction (from 40.33 +/- 11.42 to 61.00 +/- 13.68%), ratio of mitral early and
      late diastolic filling velocity (from 1.04 +/- 0.57 to 1.21 +/- 0.52), rotation
      of basal LV (from 4.48 +/- 2.66 to 5.65 +/- 2.64 degree), rotation of apical LV
      (from 4.27 +/- 3.08 to 5.50 +/- 4.25 degree), LV twist (8.75 +/- 4.45 to 11.14 +/
      5.25 degree) and torsion (from 1.06 +/- 0.54 to 1.33 +/- 0.61 degree/cm) were
      increased significantly (p < 0.05). Interventricular septum thickness (from 11.67
      +/- 2.39 to 9.67 +/- 0.48 mm), left ventricular mass index (from 104.00 +/- 16.47
      to 95.50 +/- 21.44 g/m(2)), systolic blood pressure (from 143.50 +/- 34.99 to
      121.50 +/- 7.09 mmHg), serum blood urea nitrogen (from 42.40 +/- 7.98 to 30.43 +/
      13.85 mg/dL) and creatinine (from 4.53 +/- 1.96 to 2.73 +/- 2.57 mg/dL) were
      decreased significantly (p < 0.05). CONCLUSION: Kidney transplantation in end
      stage renal disease without myocardial infarction results in improvement in left
      ventricular structure, function and myocardial mechanics as detected by
      echocardiography and velocity vector imaging. Velocity vector imaging provided
      valuable information for detection and follow-up of cardiac abnormalities in
      patients with end stage renal disease.

PMID- 24459565
TI  - Accuracy of two-dimensional speckle tracking echocardiography for the detection
      of significant coronary stenosis.
AB  - BACKGROUND: Visual assessment of wall motion abnormalities (WMA) by 2-dimensional
      echocardiography (2DE) is the most semi-quantitative method used to detect
      coronary artery disease (CAD), but it carries many limitations. Speckle tracking
      echocardiography (STE) overcomes these limitations and allows an objective
      quantification of myocardial deformation. The aim of the study to examine the
      accuracy of global and segmental longitudinal strain (LS) for the detection of
      CAD compared with visual assessment of WMA using coronary angiography as a golden
      standard. METHODS: The study enrolled 25 patients (mean age 51.0 +/- 8.7, 64% are
      male) referred to coronary angiography with clinical suspicion of CAD. 2DE
      assessment of WMA and evaluation of LS using STE were performed using left
      ventricular 17-segments models. Significant CAD was defined as >= 50% stenosis in
      one or more major coronary arteries by angiography. RESULTS: Patients were
      classified into 2 groups: group I included 15 patients with significant CAD and
      group II included 10 patients with insignificant and/or absence of CAD. WM score
      was strongly correlated with the global LS in group I and II (R = 0.80, p <
      0.0001 and R = 0.88, p < 0.0001 respectively). In all patients, 425 segments were
      analyzed. WMA was detected in 163 segments of 425 (38.3%) while abnormal LS was
      detected in 214 segments (50.3%). Compared with coronary angiography, the total
      sensitivity, specificity and accuracy for visual analysis and STE were (56%,
      88.2%, and 60% vs. 68.6%, 77%, and 81.8% respectively). CONCLUSION: Segmental LS
      is more accurate for the detection of ischemic myocardial segment corresponding
      to functionally relevant coronary anatomy than visual assessment of WM.

PMID- 24459566
TI  - Brucella endocarditis of pseudoaneurysm of an aortic composite graft.
AB  - The occurrence of Brucella endocarditis following Bentall operation is a rare and
      life threatening condition, particularly when it is complicated by development of
      a pseudoaneurysm. Here we present a 40-year-old veterinarian with bicuspid aortic
      valve, who developed type A aortic root dissection and required Bentall
      operation. His past medical history was positive for an episode of treated
      brucellosis. Four months after the operation, he developed signs, symptoms and
      serological findings of brucellosis for the second time and was treated with
      antibiotics. Then after he was well untill about 14 days prior to his recent
      admission, when he again developed hip pain, fever, shortness of breath, profound
      fatigue and weakness. His transthoracic echocardiography was suggestive of
      endocarditis. A transesophageal echocardiogram revealed detachment of valve
      conduit from the annulus and the mitral-aortic intervalvular fibrosa and the
      presence of a large aortic pseudoaneurysm with multiple vegetations attached to
      its Dacron walls. A huge pseudoaneurysm was detected at surgery and the whole
      valve-conduit was replaced with a 25 mm homograft. Blood and vegetation cultures
      turned to be positive for Brucella melitensis. Early echocardiographic diagnosis
      and prompt surgical intervention were helpful for survival of our patient who had
      aortic pseudoaneurysm complicated by Brucella endocarditis. 

PMID- 24459567
TI  - Asymptomatic myxoma originating from the right ventricular outflow tract.
AB  - Asymptomatic right ventricular outflow tract (RVOT) myxoma is quite rare. We
      report an unusual case of asymptomatic myxoma arising from the RVOT which was
      successfully surgically removed. 

PMID- 24459568
TI  - Intermittent, non cyclic severe mechanical aortic valve regurgitation.
AB  - Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus
      formation. We describe an unusual case of intermittent, non cyclic mechanical
      aortic prosthesis dysfunction due to pannus formation with thrombus in the
      absence of systolic restriction of disk excursion, that presented with
      intermittent severe aortic regurgitation. 

PMID- 24459569
TI  - Organized prosthetic tricuspid valve thrombosis treated successfully with medical
      treatment.
AB  - Prosthetic valve thrombosis (PVT) can be a life-threatening complication that
      requires immediate treatment. We present a case of 57-year-old woman with
      tricuspid PVT who was definitely diagnosed by multi-detector-row computed
      tomography limited with echocardiography. The patient was treated successfully
      with an alternative approach using low molecular weight heparin bridging therapy
      followed by intensifying anticoagulation alone. 

PMID- 24459570
TI  - The case of isolated double atrial septum with persistent interatrial space.
AB  - Double atrial septum is very rare atrial septal malformation which has double
      layered atrial septum with persistent interatrial space between the two atria.
      Clinically, most cases of this anomaly are asymptomatic unless manifest as
      thromboembolic complications, such as stroke, or transient ischemic attack, that
      thrombus may be originated from this interatrial space. We report a case of a 69
      year-old man who was diagnosed with isolated double atrial septum by
      transthoracic echocardiography. 

PMID- 24459571
TI  - Early complication of mustard procedure after late repair.

PMID- 24459572
TI  - A successful dissolution of an obstructive prosthetic mitral valve thrombus:
      sequential two and three dimensional transesophageal echocardiography
      examination.

PMID- 24459573
TI  - Is there any clinical significance of compression of left common iliac vein?

PMID- 24459574
TI  - Cervical preneoplasia biomarkers: a conundrum for the community based gynecologic
      surgical pathologist.
AB  - The integration of high-risk (HR) human papillomavirus (HPV) in the cell genome
      is an essential step in the oncogenic pathway of lower ano-genital HPV-related
      squamous preinvasive and invasive lesions. The expression of HR-HPV surrogate
      biomarkers of HR-HPV integration by immunohistocytochemistry (IHC) serves as a
      diagnostic and/or a prognostic tool of cervical preinvasive lesions. IHC is
      claimed to decrease the interobserver variability in the diagnosis of
      histomorphologically equivocal lesions, and to be helpful in evaluating the
      potentiality of regression, persistence or progression. The most common
      biomarkers used in cervical pathology are p16(INK4a), Ki-67, the HPV capsid L1
      antigen, and ProEXc. Critical review of the literature shows a great variability
      in the diagnostic accuracy, risk evaluation, and relative distribution of these
      biomarkers in low and high grade preinvasive lesions. Review of the literature
      suggests that currently dual IHC with p16 and L1 provide the best diagnostic and
      prognostic evaluation of lesions diagnosed histomorphologically as low and high
      grade. 

PMID- 24459575
TI  - Reproductive outcomes after laparoscopic radical trachelectomy for early-stage
      cervical cancer.
AB  - OBJECTIVE: The objective of this study was to estimate the reproductive outcome
      of young women with early-stage cervical cancer who underwent fertility-sparing
      laparoscopic radical trachelectomy (LRT). METHODS: We performed a retrospective
      review of the medical records of patients with early-stage cervical cancer who
      underwent LRT. Clinicopathological data were obtained from patient medical
      records, and reproductive outcome data were obtained from patient medical records
      and telephone interviews. RESULTS: Fifty-five patients who underwent successful
      LRT were included in this study. The median age of patients was 32 years (range,
      22 to 40 years), and the median follow-up time after LRT was 37 months (range, 3
      to 105 months). Menstruation resumed in all patients after LRT, with fifty
      patients (90.9%) and five patients (9.1%) reporting regular and irregular
      menstruation, respectively. Six patients (10.9%) presented with cervical
      stenosis, which was manifested by regular but decreased menstrual flow and newly
      developed dysmenorrhea. These patients underwent cervical cannulation and
      dilatation. Eighteen patients (32.7%) attempted to conceive, with six out of 18
      patients receiving fertility treatments. Fourteen pregnancies (i.e., four missed
      abortions, six preterm births and four full-term births) occurred in 10 patients
      after LRT. Nine out of 10 patients gave birth to 10 healthy babies. The pregnancy
      rate after LRT was 55.6% (10/18). The spontaneous abortion rate and live birth
      rate were 28.6% (4/14) and 71.4% (10/14), respectively. The preterm birth rate
      was 60% (6/10). CONCLUSION: Pregnancy and live birth rates after LRT were
      promising; however, the preterm birth rate was relatively high. Cervical stenosis
      also occurred in a small percentage of patients.

PMID- 24459576
TI  - Definitive extended field intensity-modulated radiotherapy and concurrent
      cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer.
AB  - OBJECTIVE: To assess the toxicity of delivering extended field intensity
      modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for
      locally advanced cervical carcinoma. METHODS: Forty-five patients who underwent
      EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to
      IIIB cervical cancer were retrospectively reviewed. The clinical target volume
      included all areas of gross and potentially microscopic disease and regional
      lymph node regions. All patients underwent high-dose-rate brachytherapy. The
      acute and late toxicity were scored using the Common Terminology Criteria for
      Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity
      scoring criteria, respectively. RESULTS: The median follow-up was 28 months
      (range, 5 to 62 months). Forty-two patients had a complete response, and three
      had a persistent disease. Of those 42 patients, 15 patients (35.7%) had
      recurrence. The regions of recurrence were in-field in 2 patients and out-field
      in 13 patients. Acute grade >=3 gastrointestinal, genitourinary and hematologic
      toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%)
      suffered from late grade 3 toxicities. Seven patients experienced ovarian
      transposition, 5 of those patients (71%) maintained ovarian function. Thirty
      eight patients (84.4%) were alive at the last follow-up. CONCLUSION: Concurrent
      cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are
      acceptable. EF-IMRT provides an opportunity to preserve endocrine function for
      patients with ovarian transposition.

PMID- 24459577
TI  - Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally
      advanced squamous cell carcinoma of the vulva.
AB  - OBJECTIVE: The therapeutic outcomes of patients with advanced vulvar cancer are
      poor. Multi-modality treatments including concurrent chemoradiation or different
      regimens of neoadjuvant chemotherapy (NACT), and surgery have been explored to
      reduce the extent of surgery and morbidity. The present single-institution trial
      aimed to evaluate the efficacy and toxicity of paclitaxel and cisplatin in
      locally advanced vulvar cancer. METHODS: From 2002 to 2009, 10 patients with
      stage III-IV locally advanced squamous cell carcinoma of the vulva were
      prospectively treated with 3 courses of paclitaxel-ifosfamide-cisplatin or
      paclitaxel-cisplatin. Nine of them subsequently underwent radical local excision
      or radical partial vulvectomy and bilateral inguino-femoral lymphadenectomy.
      RESULTS: The clinical response rate of all enrolled patients was 80%, whereas the
      pathological responses included 1 case with complete remission, 2 with persistent
      carcinoma in situ, and 6 invasive cancer cases with tumor shrinkage of more than
      50%. Four patients had positive nodes. Forty percent of patients experienced
      grade 3-4 bone marrow toxicity, which was successfully managed with granulocyte
      colony stimulating factor, even in cases of elderly patients. Median progression
      free survival after surgery was 14 months (range, 5 to 44 months). Six of the 7
      recurrent cases were local, and 3 of them were treated with salvage surgery while
      the other 3 received radiation with or without chemotherapy. After a median
      follow-up period of 40 months (range, 5 to 112 months), 55.5% of patients
      remained alive with no evidence of disease, including 2 long-term survivors after
      recurrence at 5 and 9 years. CONCLUSION: Based on the high response rate and
      manageable toxicity, NACT with paclitaxel and cisplatin with or without
      ifosfamide followed by surgery could be considered as a therapeutic option for
      locally advanced vulvar cancer.

PMID- 24459578
TI  - FIGO 1988 versus 2009 staging for endometrial carcinoma: a comparative study on
      prediction of survival and stage distribution according to histologic subtype.
AB  - OBJECTIVE: The surgical staging system for endometrial carcinoma developed by
      International Federation of Gynecology and Obstetrics (FIGO) in 1988 was revised
      in 2009. Given the importance of continuous validation of the prognostic
      performance of staging systems, we analyzed the disease specific survival for
      patients with endometrial carcinoma using FIGO 1988 and 2009 systems. Further,
      the stage distribution of endometrioid and nonendometrioid carcinomas was
      studied. METHODS: Eight hundred twenty-one women with endometrial carcinoma were
      retrospectively staged using FIGO 1988 and 2009 systems. RESULTS: FIGO 1988 IC
      was associated with an inferior survival compared with IA-IB. Survival overlapped
      for 1988 IA and IB, for 1988 IC and IIA, and for 2009 IB and II. FIGO 2009 IA-II
      patients with negative peritoneal cytology had a superior survival compared with
      1988 IIIA patients with positive cytology only. The survival was similar for 1988
      IIIA with positive cytology only and for 2009 IIIA. Cox proportional hazards
      model recognized grade 3 endometrioid and nonendometrioid histology, tumor spread
      beyond the uterine corpus and cervix, and positive peritoneal cytology as
      significant predictors of death. Among 2009 IIIC substages, the proportion of
      IIIC2 tumors was higher for nonendometrioid than for endometrioid carcinomas
      (p=0.003). CONCLUSION: Stage I with deep myometrial invasion and stage II
      endometrial carcinoma seem to have similar survival outcomes. Although positive
      peritoneal cytology does not alter the stage according to the FIGO 2009 system,
      it should be considered a poor prognostic sign. The high proportion of
      nonendometrioid carcinomas in the stage IIIC2 category may reflect different
      patterns of retroperitoneal spread among tumors with different histologic
      subtypes.

PMID- 24459579
TI  - Correlation between the overexpression of epidermal growth factor receptor and
      mesenchymal makers in endometrial carcinoma.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of
      overexpression of epidermal growth factor receptor (EGFR) on the expression of
      epithelial cell markers (E-cadherin and alpha-catenin) and mesenchymal cell
      markers (N-cadherin and vimentin) in endometrial carcinoma. METHODS: The
      expression of all 4 markers was evaluated in EGFR overexpressing Ishikawa cells,
      control Ishikawa cells, and KLE cells using reverse transcription polymerase
      chain reaction (RT-PCR) and Western blotting. The expression of these 4 markers
      was also determined in cancerous tissues of patients with endometrial carcinoma
      using immunohistochemical staining. RESULTS: Ishikawa cells transfected with EGFR
      showed decreased expression of E-cadherin and alpha-catenin and increased
      expression of N-cadherin and vimentin compared with control Ishikawa cells
      (p<0.01 for all). The expression of N-cadherin and vimentin was higher and the
      expression of E-cadherin and alpha-catenin was lower in stage II-III than stage I
      and in grade II-III than grade I endometrial carcinoma tissue (p<0.01 for all).
      CONCLUSION: Decreased expression of epithelial markers (E-cadherin and alpha
      catenin) and increased expression of mesenchymal markers (N-cadherin and
      vimentin) were observed in human endometrial carcinoma tissue. These findings
      correlate with high EGFR expression in cultured endometrial carcinoma cells.

PMID- 24459581
TI  - A longitudinal analysis with CA-125 to predict overall survival in patients with
      ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to explore the association of
      longitudinal CA-125 measurements with overall survival (OS) time by developing a
      flexible model for patient-specific CA-125 profiles, and to provide a simple and
      reliable prediction of OS. METHODS: A retrospective study was performed on 275
      patients with ovarian cancer who underwent at least one cycle of primary
      chemotherapy in our institute. Serial measurements of patients' CA-125 levels
      were performed at different frequencies according to their clinical plans. A
      statistical model coupling the Cox proportional hazards and the mixed-effects
      models was applied to determine the association of OS with patient-specific
      longitudinal CA-125 values. Stage and residual tumor size were additional
      variables included in the analysis. RESULTS: A total of 1,601 values of CA-125
      were included. Longitudinal CA-125 levels, stage, and the residual tumor size
      were all significantly associated with OS. A patient-specific survival
      probability could be calculated. Validation showed that, in average, 85.4%
      patients were correctly predicted to have a high or low risk of death at a given
      time point. Comparison with a traditional model using CA-125 half-life and time
      to reach CA-125 nadir showed that the longitudinal CA-125 model had an improved
      predicative value. CONCLUSION: Longitudinal CA-125 values, measured from the
      diagnosis of ovarian cancer to the completion of primary chemotherapy, could be
      used to reliably predict OS after adjusting for the stage and residual tumor
      disease. This model could be potentially useful in clinical counseling of
      patients with ovarian cancer.

PMID- 24459580
TI  - Survival benefit of taxane plus platinum in recurrent ovarian cancer with non
      clear cell, non-mucinous histology.
AB  - OBJECTIVE: This study was conducted to examine the effects of front-line
      chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of
      patients with recurrent ovarian cancer, when stratifying the histologic type.
      METHODS: Five hundred and seventy-four patients with recurrent ovarian cancer
      with sufficient clinical information, including front-line chemotherapy, were
      analyzed. The pathologic slides were evaluated by central pathologic review. The
      patients were divided into two groups: group A (n=261), who underwent taxane plus
      platinum, and group B (n=313), who underwent conventional platinum-based
      chemotherapy without taxanes. RESULTS: The median age was 54 years (range, 14 to
      89 years). Group A had significantly better median OS (45.0 months vs. 30.3
      months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group
      B. The OS and PRS were similar between the groups in patients with clear cell or
      mucinous histology. In contrast, among patients with non-clear cell, non-mucinous
      histologies, the OS and PRS of group A were significantly better than those of
      group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among
      patients with non-clear cell, non-mucinous histologies, chemotherapy including
      taxane and platinum was an independent predictor of favorable survival outcomes.
      Conversely, in patients with clear cell or mucinous histology, taxane-including
      platinum-based combination chemotherapy did not improve the OS and PRS compared
      to a conventional platinum-based regimen which did not include taxanes.
      CONCLUSION: Since the emergence of taxane plus platinum, the prognosis of
      patients with recurrent ovarian cancer has improved. However, we here demonstrate
      that this improvement is limited to patients with non-clear cell, non-mucinous
      histologies.

PMID- 24459582
TI  - Decreased ARID1A expression is correlated with chemoresistance in epithelial
      ovarian cancer.
AB  - OBJECTIVE: Loss of ARID1A is related to oncogenic transformation of ovarian clear
      cell adenocarcinoma. The present study was conducted in epithelial ovarian cancer
      of all tissue types to investigate whether an increased or decreased expression
      level of ARID1A can be a prognostic factor for ovarian cancer or can influence
      the sensitivity to anticancer drugs. METHODS: The expression level of ARID1A was
      investigated in 111 patients with epithelial ovarian cancer who received initial
      treatment at the Hirosaki University Hospital between 2006 and 2011. The
      expression level of ARID1A was immunohistochemically graded using staining
      scores, which were calculated by multiplying the staining intensity of the nuclei
      by the stain-positive area. RESULTS: The level of ARID1A was significantly lower
      in clear cell adenocarcinoma than in other histologic types. Among the patients
      with stage III, IV cancer (n=46), the level of ARID1A was significantly lower
      (p=0.026) in patients who did not achieve complete response (CR; n=12) than in
      patients who achieved CR (n=34). The level of ARID1A was relatively lower
      (p=0.07) in patients who relapsed after achieving CR (n=21) than in patients who
      did not relapse (n=13). When the staining score of 0 was defined as ARID1A
      negative and other staining scores were defined as ARID1A-positive, there was
      significant difference in progression-free survival between ARID1A-negative
      (n=11) and ARID1A-positive (n=35) patients in stage III, IV disease. CONCLUSION:
      The result suggests that decreased ARID1A expression is correlated with
      chemoresistance and may be a predictive factor for the risk of relapse of
      advanced cancer after achieving CR.

PMID- 24459583
TI  - Surgical anatomy of the common iliac veins during para-aortic and pelvic
      lymphadenectomy for gynecologic cancer.
AB  - OBJECTIVE: Compression of the left common iliac vein between the right common
      iliac artery and the vertebrae is known to be associated with the occurrence of
      left iliofemoral deep vein thrombosis (DVT). In this study, we described the
      variability in vascular anatomy of the common iliac veins and evaluated the
      relationship between the degree of iliac vein compression and the presence of DVT
      using the data from surgeries for gynecologic cancer. METHODS: The anatomical
      variations and the degrees of iliac vein compression were determined in 119
      patients who underwent systematic para-aortic and pelvic lymphadenectomy during
      surgery for primary gynecologic cancer. Their medical records were reviewed with
      respect to patient-, disease-, and surgery-related data. RESULTS: THE DEGREES OF
      COMMON ILIAC VEIN COMPRESSION WERE CLASSIFIED INTO THREE GRADES: grade A (n=28,
      23.5%), with a calculated percentage of 0%-25% compression; grade B (n=47,
      39.5%), with a calculated percentage of 26%-50% compression; and grade C (n=44,
      37%), with a calculated percentage of more than 50% compression. Seven patients
      (5.9%) had common iliac veins with anomalous anatomies; three were divided into
      small caliber vessels, two with a flattened structure, and two had double
      inferior vena cavae. The presence of DVT was associated with the elevated D-dimer
      levels but not with the degree of iliac vein compression in this series.
      CONCLUSION: Although severe compression of the common iliac veins was frequently
      observed, the degree of compression might not be associated with DVT in surgical
      patients with gynecologic cancer. Anomalous anatomies of common iliac veins
      should be considered during systematic para-aortic and pelvic lymphadenectomy in
      the gynecologic cancer patients.

PMID- 24459584
TI  - Epidemiologic characteristics of cervical cancer in Korean women.
AB  - Cervical cancer is the most common female genital tract malignancy in Korean
      women. Although age-standardized cancer incidence rate of cervical cancer has
      decreased from 18.6 per 100,000 women in 1999 to 12.3 per 100,000 women in 2010
      in Korea with widespread routine screening, several epidemiologic characteristics
      are still present. Incidence of cervical cancer still varies according to
      geographic area, and a significant portion of cases are detected at a
      locoregionally advanced stage, without significant improvement of five-year
      survival rate.2014-01-15 Cervical screening techniques such as the Pap smear
      should be the gold standard strategy to decrease incidence and to improve the
      survival outcomes of patients with cervical cancer. In addition, screening
      programs for cervical cancer should be designed, organized and directed within
      the context of a nationwide program for cancer control. 

PMID- 24459585
TI  - A mechanical micro molecular mass sensor.
AB  - One of the bio-sensing mechanisms is mechanical. Rather than measuring shift in
      resonance frequency, we adopt to measure the change in spring constant due to
      adsorption, as one of the fundamental sensing mechanism. This study explains
      determination of spring constant of a surface functionalized micro machined micro
      cantilever, which resonates in a trapezoidal cavity-on Silicon <100> wafer, with
      the resonating frequency of 7000 cycles per second. This thin-flimsy-oxide micro
      cantilever has a typical shape, and the tip of the micro-cantilever is dip-coated
      with chemically and biologically active material. The change in mass, due to
      adsorption, is detected by measuring the change in spring constant. The Force
      Distance spectroscopy is used to detect the change in spring constant. The
      experimental results, show that the mechanical sensing scheme used, permit this
      surface functionalized micro machined micro cantilever to be used as a molecular
      mass sensor. The mechanical spring behaviour of a micro-cantilever, a micro
      mechanical device can be used to develop ultra-tech micro-mechanical system using
      computer interface.

PMID- 24459586
TI  - Diabetes and hemoglobin a1c as risk factors for nosocomial infections in
      critically ill patients.
AB  - Objective. To evaluate whether diabetes mellitus (DM) and hemoglobin A1c (HbA1c)
      are risk factors for ventilator-associated pneumonia (VAP) and bloodstream
      infections (BSI) in critically ill patients. Methods. Prospective observational
      study; patients were recruited from the intensive care unit (ICU) of a general
      district hospital between 2010 and 2012. INCLUSION CRITERIA: ICU hospitalization
      >72 hours and mechanical ventilation >48 hours. HbA1c was calculated for all
      participants. DM, HbA1c, and other clinical and laboratory parameters were
      assessed as risk factors for VAP or BSI in ICU. Results. The overall ICU
      incidence of VAP and BSI was 26% and 30%, respectively. Enteral feeding OR
      (95%CI) 6.20 (1.91-20.17; P = 0.002) and blood transfusion 3.33 (1.23-9.02; P =
      0.018) were independent risk factors for VAP. BSI in ICU (P = 0.044) and ICU
      mortality (P = 0.038) were significantly increased in diabetics. Independent risk
      factors for BSI in ICU included BSI on admission 2.45 (1.14-5.29; P = 0.022) and
      stroke on admission2.77 (1.12-6.88; P = 0.029). Sepsis 3.34 (1.47-7.58; P =
      0.004) and parenteral feeding 6.29 (1.59-24.83; P = 0.009) were independently
      associated with ICU mortality. HbA1c >= 8.1% presented a significant diagnostic
      performance in diagnosing repeated BSI in ICU. Conclusion. DM and HbA1c were not
      associated with increased VAP or BSI frequency. HbA1c was associated with
      repeated BSI episodes in the ICU.

PMID- 24459587
TI  - Content analysis of work limitation, stanford presenteeism, and work instability
      questionnaires using international classification of functioning, disability, and
      health and item perspective framework.
AB  - Background. Presenteeism refers to reduced performance or productivity while at
      work due to health reasons. WLQ-26, SPS-6, and RA-WIS are the commonly used self
      report presenteeism questionnaires. These questionnaires have acceptable
      psychometric properties but have not been subject to structured content analysis
      that would define their conceptual basis. Objective. To describe the conceptual
      basis of the three questionnaires using ICF and IPF and then compare the
      distribution and content of codes to those on the vocational rehabilitation core
      set. Methods. Two researchers independently linked the items of the WLQ-26, SPS
      6, and RA-WIS to the ICF and IPF following the established linking rules. The
      percentage agreement on coding was calculated between the researchers. Results.
      WLQ-26 was linked to 62 ICF codes, SPS-6 was linked to 17 ICF codes, and RA-WIS
      was linked to 74 ICF codes. Most of these codes belonged to the activity and
      participation domains. All the concepts were classified by the IPF, and the most
      were rational appraisals within the social domain. Only 12% of codes of the core
      set for vocational rehabilitation were used in this study to code these
      questionnaires. Conclusion. The specific nature of work disability that was
      included in these three questionnaires was difficult to explain using ICF since
      many aspects of content were not confined. The core set for vocational
      rehabilitation covered very limited content of the WLQ-26, SPS-6, and RA-WIS. 

PMID- 24459588
TI  - Immediate beneficial effects of mental rotation using foot stimuli on upright
      postural stability in healthy participants.
AB  - The present study was designed to investigate whether an intervention during
      which participants were involved in mental rotation (MR) of a foot stimulus would
      have immediate beneficial effects on postural stability (Experiment 1) and to
      confirm whether it was the involvement of MR of the foot, rather than simply
      viewing foot stimuli, that could improve postural stability (Experiment 2). Two
      different groups of participants (n = 16 in each group) performed MR intervention
      of foot stimuli in each of the two experiments. Pre- and postmeasurements of
      postural stability during unipedal and bipedal standing were made using a force
      plate for the intervention. Consistently, postural sway values for unipedal
      standing, but not for bipedal standing, were decreased immediately after the MR
      intervention using the foot stimuli. Such beneficial effects were not observed
      after the MR intervention using car stimuli (Experiment 1) or when participants
      observed the same foot stimuli during a simple reaction task (Experiment 2).
      These findings suggest that the MR intervention using the foot stimuli could
      contribute to improving postural stability, at least when it was measured
      immediately after the intervention, under a challenging standing condition (i.e.,
      unipedal standing). 

PMID- 24459589
TI  - Force transfer and stress distribution in an implant-supported overdenture
      retained with a hader bar attachment: a finite element analysis.
AB  - Background and Objectives. A key factor for the long-term function of a dental
      implant is the manner in which stresses are transferred to the surrounding bone.
      The effect of adding a stiffener to the tissue side of the Hader bar helps to
      reduce the transmission of the stresses to the alveolar bone. But the ideal
      thickness of the stiffener to be attached to the bar is a subject of much debate.
      This study aims to analyze the force transfer and stress distribution of an
      implant-supported overdenture with a Hader bar attachment. The stiffener of the
      bar attachments was varied and the stress distribution to the bone around the
      implant was studied. Methods. A CT scan of edentulous mandible was used and three
      models with 1, 2, and 3 mm thick stiffeners were created and subjected to loads
      of emulating the masticatory forces. These different models were analyzed by the
      Finite Element Software (Ansys, Version 8.0) using von Mises stress analysis.
      Results. The results showed that the maximum stress concentration was seen in the
      neck of the implant for models A and B. In model C the maximum stress
      concentration was in the bar attachment making it the model with the best stress
      distribution, as far as implant failures are concerned. Conclusion. The implant
      with Hader bar attachment with a 3 mm stiffener is the best in terms of stress
      distribution, where the stress is concentrated at the bar and stiffener regions. 

PMID- 24459590
TI  - Two cases and review of the literature: primary percutaneous angiography and
      antiplatelet management in patients with immune thrombocytopenic purpura.
AB  - We report two cases of immune thrombocytopenic purpura (ITP) associated with
      acute coronary artery syndrome highlighting the interventions done in every case
      along with the medications used during intervention and as outpatient. The first
      case is that of a woman with ITP exacerbation while on dual antiplatelet therapy
      and the second case is that of a male presenting with non-ST elevation myocardial
      infarction (NSTEMI) while in a thrombocytopenic crisis. In both cases
      antiplatelet therapy was held and thrombopoietic therapy was initiated before
      resuming full anticoagulation and coronary intervention. Given the paucity of
      data on ITP and antiplatelets treatment in the setting of acute coronary
      syndrome, no strict recommendations can be proposed, but antiplatelets appear to
      be safe acutely and in the long term in this category of patients as long as few
      measures are undertaken to minimize the risks of bleeding and thrombosis. 

PMID- 24459592
TI  - A Rare Presentation of Community Acquired Methicillin Resistant Staphylococcus
      aureus.
AB  - Prostatic abscess is a rarely described condition and is commonly caused by gram
      negative organisms such as enterobacteria. However, as the prevalence of
      methicillin resistant Staphylococcus aureus (MRSA) increases in the community,
      unusual infections due to this organism have been recently published. In this
      report, we describe a patient with diabetes mellitus type 2, who presents with
      diabetic ketoacidosis-later found to be due to a prostatic abscess from which
      MRSA was cultured. 

PMID- 24459591
TI  - Formulation strategies to improve the bioavailability of poorly absorbed drugs
      with special emphasis on self-emulsifying systems.
AB  - Poorly water-soluble drug candidates are becoming more prevalent. It has been
      estimated that approximately 60-70% of the drug molecules are insufficiently
      soluble in aqueous media and/or have very low permeability to allow for their
      adequate and reproducible absorption from the gastrointestinal tract (GIT)
      following oral administration. Formulation scientists have to adopt various
      strategies to enhance their absorption. Lipidic formulations are found to be a
      promising approach to combat the challenges. In this review article, potential
      advantages and drawbacks of various conventional techniques and the newer
      approaches specifically the self-emulsifying systems are discussed. Various
      components of the self-emulsifying systems and their selection criteria are
      critically reviewed. The attempts of various scientists to transform the liquid
      self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption,
      spray drying, lyophilization, melt granulation, extrusion, and so forth to
      formulate various dosage forms like self emulsifying capsules, tablets,
      controlled release pellets, beads, microspheres, nanoparticles, suppositories,
      implants, and so forth have also been included. Formulation of SEDDS is a
      potential strategy to deliver new drug molecules with enhanced bioavailability
      mostly exhibiting poor aqueous solubility. The self-emulsifying system offers
      various advantages over other drug delivery systems having potential to solve
      various problems associated with drugs of all the classes of biopharmaceutical
      classification system (BCS). 

PMID- 24459593
TI  - Recurrent Mitral Valve Endocarditis Caused by Streptococcus pneumoniae in a
      Splenectomized Host.
AB  - A 72-year-old male with a remote history of splenectomy and two previous episodes
      of pneumococcal endocarditis of mitral valve presented with high-grade fever and
      confusion for 3 days. Nine months priorly, patient underwent mitral valve repair
      when he had the first episode of pneumococcal mitral valve endocarditis. He
      received pneumococcal vaccination two years ago. On examination during this
      admission, he was found to be febrile (104.3 F) and confused and had a grade 2/6
      systolic murmur at the apex without any radiation. Laboratory data was
      significant for a white blood cell count of 22,000/mm(3) (normal: 4000
      11000/mm(3)). Blood cultures (4/4 bottles) grew penicillin-sensitive
      Streptococcus pneumoniae. Transesophageal echocardiogram revealed small
      vegetation on the posterior mitral leaflet without any evidence of abscess and
      severe mitral regurgitation. Patient clinically responded to intravenous
      ceftriaxone. However, due to recurrent pneumococcal mitral valve endocarditis and
      severe mitral regurgitation, the patient underwent mitral valve replacement.
      Patient had an uneventful recovery and was discharged home. Pneumococcal
      endocarditis itself is being uncommon in this current, penicillin, era; our case
      highlights the recurrent nature of pneumococcal endocarditis in a splenectomized
      host and the importance of pursuing aggressive treatment options in this clinical
      scenario. 

PMID- 24459594
TI  - Adenofibroma in a young patient: a rare entity in an uncommon age.
AB  - Adenofibroma is an extremely uncommon benign tumor composed of glandular and
      fibrous tissues. It occurs more often in the endometrium but it can also occur in
      the cervix and extrauterine sites. We report a case of a 32-year-old asymptomatic
      woman with cervical adenofibroma, first detected in a routine endovaginal
      ultrasound, as a cervical mass containing multiple cystic components.
      Histopathologic findings diagnosed its nature. As adenofibromas are very rare, we
      present this case with a brief review of the literature. 

PMID- 24459595
TI  - Pregnancy complicated by portal hypertension secondary to biliary atresia.
AB  - Biliary atresia is a rare idiopathic neonatal cholestatic disease characterized
      by the destruction of both the intra- and extrahepatic biliary ducts. As the
      disease is progressive all cases will develop portal fibrosis, cirrhosis, and
      portal hypertension with the sequelae of varices, jaundice, and eventually liver
      failure requiring a transplant. Survival rates have improved considerably with
      many females living well in to be childbearing age. Due to the complexity of the
      disease these pregnancies are considered, high risk. We report the antenatal,
      intrapartum, and postpartum managements of a pregnancy complicated by biliary
      atresia. Furthermore, we highlight the importance of a multidisciplinary team
      approach in optimizing obstetric care for this high risk group. 

PMID- 24459596
TI  - Persistent primitive trigeminal artery: an unusual cause of vascular tinnitus.
AB  - Pulsatile tinnitus is generally of vascular origin and can be due to arterial,
      venous, or systemic causes. While certain congenital anatomical variants and
      arterial vascular loops have been commonly found in symptomatic patients
      undergoing imaging, persistent primitive trigeminal artery in association with
      isolated tinnitus is unusual. Thus we report a patient with unilateral isolated
      pulsatile tinnitus who was evaluated with magnetic resonance angiography and was
      found to have a persistent primitive trigeminal artery. We also briefly discuss
      vascular tinnitus as well as the embryology, imaging, and classification of
      persistent primitive trigeminal artery with the clinical implications. 

PMID- 24459597
TI  - Myofibroblastoma of the female breast with admixed but distinct foci of spindle
      cell lipoma: a case report.
AB  - Mammary myofibroblastoma (MFB) is a rare benign spindle neoplasm that affects
      both sexes with a male predominance. It can exhibit a wide range of histological
      patterns. We report a case of epithelioid/spindle MFB of the female breast with
      admixed, but distinct, foci of spindle cell lipoma. Whilst all the spindle cells
      within the tumour expressed CD34, AR, ER, BCL2, and CD10, only those within the
      myofibroblastoma expressed desmin and only those within the lipomatous areas
      expressed S100. This finding, to our knowledge, is a novel one that has not been
      reported before. 

PMID- 24459598
TI  - Myolipoma of mesentery: a case report.
AB  - Myolipomas are very rare benign lipomatous soft tissue tumors which are usually
      located in retroperitoneum, abdominal and pelvic cavity, and the abdominal wall.
      They can be diagnosed histologically by the presence of irregularly admixed
      mature adipose tissue and smooth muscle fibers. The correct diagnosis of
      myolipoma is important, because it should be considered in the differential
      diagnosis of fat-containing lesions of the soft tissue and should follow a benign
      clinical course despite its frequently large size and deep location. We report
      here a case of myolipoma arising in the mesentery of the jejunum. 

PMID- 24459599
TI  - The impacts of cardiac rehabilitation program on echocardiographic parameters in
      coronary artery disease patients with left ventricular dysfunction.
AB  - Introduction. The accurate impact of exercise on coronary artery disease (CAD)
      patients with left ventricular dysfunction is still debatable. We studied the
      effects of cardiac rehabilitation (CR) on echocardiography parameters in CAD
      patients with ventricular dysfunction. Methods. Patients with CAD who had
      ventricular dysfunction were included into an exercise-based rehabilitation
      program and received rehabilitation for eight weeks. All subjects underwent
      echocardiography before and at the end of the rehabilitation program. The
      echocardiography parameters, including left ventricular ejection fraction (LVEF),
      LV end-diastolic (LVEDD) and end-systolic diameters (LVESD), and peak exercise
      capacity measured in metabolic equivalents (METs), were assessed. Results.
      Seventy patients (mean age = 57.5 +/- 10.2 years, 77.1% males) were included into
      the study. At the end of rehabilitation period, the LVEF increased from 45.14 +/-
      5.77% to 50.44 +/- 8.70% (P < 0.001), and the peak exercise capacity increased
      from 8.00 +/- 2.56 to 10.08 +/- 3.00 METs (P < 0.001). There was no significant
      change in LVEDD (54.63 +/- 12.96 to 53.86 +/- 8.95 mm, P = 0.529) or in LVESD
      (38.91 +/- 10.83 to 38.09 +/- 9.04 mm, P = 0.378) after rehabilitation.
      Conclusion. Exercise training in postmyocardial infarction patients with
      ventricular dysfunction could have beneficial effects on cardiac function without
      adversely affecting LV remodeling or causing serious cardiac complications. 

PMID- 24459600
TI  - Similarities and Differences between the Pathogenesis and Pathophysiology of
      Diastolic and Systolic Heart Failure.
AB  - Pathophysiology of heart failure has been considered to be a damaged state of
      systolic function of the heart followed by a state of low cardiac output that is,
      systolic heart failure. Even if systolic function is preserved, left ventricular
      filling in diastole can be impeded and resulted in elevation of filling pressure
      and symptoms of heart failure. This kind of heart failure is called diastolic
      heart failure. Nowadays, diastolic heart failure is referred to as heart failure
      with preserved ejection fraction (HFpEF), whereas systolic heart failure is
      referred to as heart failure with reduced ejection fraction (HFrEF). In this
      paper, the similarities and differences between the pathogenesis and
      pathophysiology of diastolic and systolic heart failure were reviewed. Although
      diastolic heart failure is a common condition of heart failure worldwide, its
      pathophysiology has not been sufficiently elucidated. This is thought to be the
      most significant reason for a lack of established treatment methods for diastolic
      heart failure. We hope to proceed with future studies on this topic. 

PMID- 24459601
TI  - A Comparison of Hemoglobin A2 Levels in Untreated and Treated Groups of HIV
      Patients on ART Including Zidovudine.
AB  - Objective. To assess the level of haemoglobin A2 in HIV patients on
      antiretroviral therapy (ART) including zidovudine with untreated HIV patients.
      Material and Methods. The study was a case control study. A total of 185 patients
      were included in the study; the case group included 125 HIV patients who were on
      antiretroviral therapy (ART) including zidovudine and 60 were in the control
      group who were not receiving ART. The high-performance liquid chromatography
      (HPLC) was done and hemoglobin A2 level was observed; value more than 3.5% was
      considered significant. The Hb A2 percentages of HIV patients were compared with
      those of control using an unpaired t-test. Results. The mean of Hb A2 in case
      group was 3.462% (SD 0.675) and in control group it was 2.815% (SD0.246). The
      higher Hb A2 value was seen in significant number of treated patients than
      control group (P < 0.0001). Conclusion. The clinicians, pathologists,
      haematologists, and genetic counsellors should be aware of effects of nutritional
      anaemia and ART on Hb A2 to reduce the chances of misdiagnosis of beta 
      thalassaemia especially in developing countries and for centres for antenatal
      screening. 

PMID- 24459603
TI  - Capnography Primer for Oral and Maxillofacial Surgery: Review and Technical
      Considerations.

PMID- 24459604
TI  - Updates on Hepato-Renal Syndrome.
AB  - Hepato-renal syndrome (HRS) is one of the most detrimental conditions in patients
      with end stage liver failure. Historically, HRS was considered a terminal disease
      associated with cirrhosis and was termed "liver-death syndrome". Furthermore,
      despite the improved understanding of pathophysiology and the reversibility of
      renal dysfunction in HRS, mortality remains extremely high especially for type 1
      HRS. This review summarizes the recent advances in the pathophysiology, diagnosis
      and management of HRS and also provides an evolving area of research in the
      pathophysiologic mechanisms of HRS, which may open the door for new therapeutic
      approaches.

PMID- 24459605
TI  - Effects of a One Year Intensive Multidisciplinary Rehabilitation Program for
      Patients with Huntington's Disease: a Prospective Intervention Study.
AB  - OBJECTIVE: To assess the effects of an intensive, multidisciplinary
      rehabilitation program for patients with early to mid-stage Huntington's disease.
      DESIGN: A prospective intervention study. SETTING: Two Norwegian inpatient
      rehabilitation centers. SUBJECTS: 37 patients, with early- to midstage
      Huntington's disease Interventions: A one year rehabilitation program, consisting
      of three admissions of three weeks each, and a five-day evaluation stay
      approximately 3 months after the last rehabilitation admission. Focus was on
      physical exercise, social activities, and group/teaching sessions. There was also
      emphasis to implement of coordinated health care and social services for the
      patients. MAIN OUTCOME MEASURES: standard measures for motor function, including
      gait and balance, cognitive function, including MMSE and UHDRS cognitive
      assessment, anxiety and depression, activities of daily living (ADL), health
      related quality of life and Body Mass Index (BMI). RESULTS: Significant
      improvements were observed in gait function, balance, in physical quality of
      life, anxiety and depression, as well as in BMI. ADL-function remained stable
      with no significant decline. Only one cognitive measure (SDMT) showed significant
      decline, while no decline was observed for the remaining cognitive measures.
      CONCLUSION: A multidisciplinary intensive rehabilitation program in patients with
      early and mid stage HD is associated with improved balance, gait function,
      physical quality of life and with reduced depressive and anxiety symptoms. Longer
      follow-up is needed to assess if these positive effects are sustained. There
      should be emphasis to establishment of long term and coordinated health care
      services for the HD patient.

PMID- 24459602
TI  - The role of the intraplaque vitamin d system in atherogenesis.
AB  - Vitamin D has been shown to play critical activities in several physiological
      pathways not involving the calcium/phosphorus homeostasis. The ubiquitous
      distribution of the vitamin D receptor that is expressed in a variety of human
      and mouse tissues has strongly supported research on these "nonclassical"
      activities of vitamin D. On the other hand, the recent discovery of the
      expression also for vitamin D-related enzymes (such as 25-hydroxyvitamin D-1
      alpha -hydroxylase and the catabolic enzyme 1,25-dihydroxyvitamin D-24
      hydroxylase) in several tissues suggested that the vitamin D system is more
      complex than previously shown and it may act within tissues through autocrine and
      paracrine pathways. This updated model of vitamin D axis within peripheral
      tissues has been particularly investigated in atherosclerotic pathophysiology.
      This review aims at updating the role of the local vitamin D within
      atherosclerotic plaques, providing an overview of both intracellular mechanisms
      and cell-to-cell interactions. In addition, clinical findings about the potential
      causal relationship between vitamin D deficiency and atherogenesis will be
      analysed and discussed. 

PMID- 24459606
TI  - The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular
      Dystrophy.
AB  - Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular,
      zebrafish provide a system for rapid, easy, and low-cost screening of small
      molecules that can ameliorate muscle damage in dystrophic larvae. Here we
      identify an optimal anti-sense morpholino cocktail that robustly knocks down
      zebrafish Dystrophin (dmd-MO). We use two approaches, muscle birefringence and
      muscle actin expression, to quantify muscle damage and show that the dmd-MO
      dystrophic phenotype closely resembles the zebrafish dmd mutant phenotype. We
      then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown
      to ameliorate the mdx mouse Duchenne model, can rescue muscle fiber damage in
      both dmd-MO and dmd mutant larvae. Our study identifies optimal morpholino and
      phenotypic scoring approaches for dystrophic zebrafish, further enhancing the
      zebrafish dmd model for rapid and cost-effective small molecule screening.

PMID- 24459607
TI  - Validity, Reliability, and Sensitivity of a 3D Vision Sensor-based Upper
      Extremity Reachable Workspace Evaluation in Neuromuscular Diseases.
AB  - INTRODUCTION: One of the major challenges in the neuromuscular field has been
      lack of upper extremity outcome measures that can be useful for clinical
      therapeutic efficacy studies. Using vision-based sensor system and customized
      software, 3-dimensional (3D) upper extremity motion analysis can reconstruct a
      reachable workspace as a valid, reliable and sensitive outcome measure in various
      neuromuscular conditions where proximal upper extremity range of motion and
      function is impaired. METHODS: Using a stereo-camera sensor system, 3D reachable
      workspace envelope surface area normalized to an individual's arm length
      (relative surface area: RSA) to allow comparison between subjects was determined
      for 20 healthy controls and 9 individuals with varying degrees of upper extremity
      dysfunction due to neuromuscular conditions. All study subjects were classified
      based on Brooke upper extremity function scale. Right and left upper extremity
      reachable workspaces were determined based on three repeated measures. The RSAs
      for each frontal hemi-sphere quadrant and total reachable workspaces were
      determined with and without loading condition (500 gram wrist weight). Data were
      analyzed for assessment of the developed system and validity, reliability, and
      sensitivity to change of the reachable workspace outcome. RESULTS: The mean total
      RSAs of the reachable workspace for the healthy controls and individuals with NMD
      were significantly different (0.586 +/- 0.085 and 0.299 +/- 0.198 respectively;
      p<0.001). All quadrant RSAs were reduced for individuals with NMDs compared to
      the healthy controls and these reductions correlated with reduced upper limb
      function as measured by Brooke grade. The upper quadrants of reachable workspace
      (above the shoulder level) demonstrated greatest reductions in RSA among subjects
      with progressive severity in upper extremity impairment. Evaluation of the
      developed outcomes system with the Bland-Altman method demonstrated narrow 95%
      limits of agreement (LOA) around zero indicating high reliability. In addition,
      the intraclass correlation coefficient (ICC) was 0.97. Comparison of the
      reachable workspace with and without loading condition (wrist weight) showed
      significantly greater RSA reduction in the NMD group than the control group
      (p<0.012), with most of the workspace reduction occurring in the ipsilateral
      upper quadrant relative to the tested arm (p<0.001). Reduction in reachable
      workspace due to wrist weight was most notable in those subjects with NMD with
      marginal strength reserve and moderate degree of impairment (Brooke = 2) rather
      than individuals with mild upper extremity impairment (Brooke = 1) or individuals
      who were more severely impaired (Brooke =3). DISCUSSION: The developed reachable
      workspace evaluation method using scalable 3D vision technology appears promising
      as an outcome measure system for clinical studies. A rationally-designed
      combination of upper extremity outcome measures including a region-specific
      global upper extremity outcome measure, such as the reachable workspace,
      complemented by targeted disease- or function-specific endpoints, may be optimal
      for future clinical efficacy trials.

PMID- 24459609
TI  - JAK/STAT Signalling in Huntington's Disease Immune Cells.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a
      CAG repeat expansion in the huntingtin (HTT) gene. Both central and peripheral
      innate immune activation have been described as features of the disease. Isolated
      human HD monocytes have been shown to produce more cytokines upon LPS stimulation
      compared to control monocytes. Understanding alterations in the signalling
      cascades responsible and activated by this increase in pro-inflammatory cytokine
      production is crucial in understanding the molecular basis of this phenomenon.
      Here we investigated the signalling cascade most commonly activated by pro
      inflammatory cytokines such as IL-6 - the JAK/STAT signalling cascade. Using flow
      cytometry, we show that one out of three key transcription factors activated by
      JAK/STAT signalling is altered in primary human HD innate immune cells,
      suggesting that this pathway may only play a minor, additive role in the immune
      cell dysfunction in HD. 

PMID- 24459608
TI  - SLCO1B1 Polymorphisms and Statin-Induced Myopathy.
AB  - Statin drugs are highly effective in lowering blood concentrations of LDL
      cholesterol, with concomitant reduction in risk of major cardiovascular events.
      Although statins are generally regarded as safe and well-tolerated, some users
      develop muscle symptoms that are mostly mild but in rare cases can lead to life
      threatening rhabdomyolysis. The SEARCH genome-wide association study, which has
      been independently replicated, found a significant association between the
      rs4149056 (c.521T>C) single-nucleotide polymorphism (SNP) in the SLCO1B1 gene,
      and myopathy in individuals taking 80 mg simvastatin per day, with an odds ratio
      of 4.5 per rs4149056 C allele. The purpose of this paper is to assemble evidence
      relating to the analytical validity, clinical validity and clinical utility of
      using SLCO1B1 rs4149056 genotyping to inform choice and dose of statin treatment,
      with the aim of minimising statin-induced myopathy and increasing adherence to
      therapy. Genotyping assays for the rs4149056 SNP appear to be robust and
      accurate, though direct evidence for the performance of array-based platforms in
      genotyping individual SNPs was not found. Using data from the SEARCH study,
      calculated values for the clinical sensitivity, specificity, positive- and
      negative-predictive values of a test for the C allele to predict definite or
      incipient myopathy during 5 years of 80 mg/day simvastatin use were 70.4%, 73.7%,
      4.1% and 99.4% respectively. There is a need for studies comparing the clinical
      validity of SLCO1B1 rs4149056 genotyping with risk scores for myopathy based on
      other factors such as racial background, statin type and dose, gender, body mass
      index, co-medications and co-morbidities. No direct evidence was found for
      clinical utility of statin prescription guided by SLCO1B1 genotype. 

PMID- 24459610
TI  - The perfect storm of information: combining traditional and non-traditional data
      sources for public health situational awareness during hurricane response.
AB  - BACKGROUND: Hurricane Isaac made landfall in southeastern Louisiana in late
      August 2012, resulting in extensive storm surge and inland flooding. As the lead
      federal agency responsible for medical and public health response and recovery
      coordination, the Department of Health and Human Services (HHS) must have
      situational awareness to prepare for and address state and local requests for
      assistance following hurricanes. Both traditional and non-traditional data have
      been used to improve situational awareness in fields like disease surveillance
      and seismology. This study investigated whether non-traditional data (i.e.,
      tweets and news reports) fill a void in traditional data reporting during
      hurricane response, as well as whether non-traditional data improve the
      timeliness for reporting identified HHS Essential Elements of Information (EEI).
      METHODS: HHS EEIs provided the information collection guidance, and when the
      information indicated there was a potential public health threat, an event was
      identified and categorized within the larger scope of overall Hurricane Issac
      situational awareness. Tweets, news reports, press releases, and federal
      situation reports during Hurricane Isaac response were analyzed for information
      about EEIs. Data that pertained to the same EEI were linked together and given a
      unique event identification number to enable more detailed analysis of source
      content. Reports of sixteen unique events were examined for types of data sources
      reporting on the event and timeliness of the reports. RESULTS: Of these sixteen
      unique events identified, six were reported by only a single data source, four
      were reported by two data sources, four were reported by three data sources, and
      two were reported by four or more data sources. For five of the events where news
      tweets were one of multiple sources of information about an event, the tweet
      occurred prior to the news report, press release, local government?emergency
      management tweet, and federal situation report. In all circumstances where
      citizens were reporting along with other sources, the citizen tweet was the
      earliest notification of the event. CONCLUSION: Critical information is being
      shared by citizens, news organizations, and local government representatives. To
      have situational awareness for providing timely, life-saving public health and
      medical response following a hurricane, this study shows that non-traditional
      data sources should augment traditional data sources and can fill some of the
      gaps in traditional reporting. During a hurricane response where early event
      detection can save lives and reduce morbidity, tweets can provide a source of
      information for early warning. In times of limited budgets, investing technical
      and personnel resources to efficiently and effectively gather, curate, and
      analyze non-traditional data for improved situational awareness can yield a high
      return on investment.

PMID- 24459611
TI  - Reverse transcription recombinase polymerase amplification assay for the
      detection of middle East respiratory syndrome coronavirus.
AB  - The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the
      eastern Mediterranean and imported cases to Europe has alerted public health
      authorities. Currently, detection of MERS-CoV in patient samples is done by real
      time RT-PCR. Samples collected from suspected cases are sent to highly-equipped
      centralized laboratories for screening. A rapid point-of-care test is needed to
      allow more widespread mobile detection of the virus directly from patient
      material. In this study, we describe the development of a reverse transcription
      isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the
      identification of MERS-CoV. A partial nucleocapsid gene RNA molecular standard of
      MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42
      degrees C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA
      molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The
      MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several
      coronaviruses and respiratory viruses affecting humans nor of the human genome.
      The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular
      MERS-CoV monitoring in acute patients and may also facilitate the search for the
      animal reservoir of MERS-CoV. 

PMID- 24459612
TI  - A randomized, double-blind trial of lisinopril and losartan for the treatment of
      cardiomyopathy in duchenne muscular dystrophy.
AB  - OBJECTIVES: This study sought to compare the effectiveness and safety of an
      angiotensin converting enzyme inhibitor (ACE-I) (lisinopril) vs. an angiotensin
      receptor blocker (ARB) (losartan) for the treatment of cardiomyopathy (CM) in
      boys with Duchenne muscular dystrophy (DMD). BACKGROUND: Development of CM is
      universal in boys with DMD. ACE-I and ARB have both been suggested as effective
      treatment options. ARBs have been associated with skeletal muscle regeneration in
      a mouse model of DMD. The question of which, if either, is more effective for CM
      treatment in DMD remains. The purpose of this multicenter double-blind
      prospective study was to compare efficacy and safety of lisinopril versus
      losartan in the treatment of newly diagnosed CM in boys with DMD. METHODS:
      Echocardiographic technician inter- and intraobserver variability were tested on
      2 separate days on 2 different boys with DMD CM. Results were compared with
      paired t-testing. Twenty-two boys with newly diagnosed DMD CM (echocardiographic
      ejection fraction (EF) 10% EF drop. Three boys in the aCE-I group had 3 visits,
      due to study funding termination. Two were withdrawn because of low EF. All their
      data are included in the analysis for as long as they remained in the study. Mean
      EF's were similar at baseline (47.5%- ACE-I, 48.4%- ARB). After 1 year each group
      significantly improved to 54.6% and 55.2% respectively (p=.02). There was no
      difference between the 2 treatment groups at 1 year. CONCLUSIONS: Inter-observer
      and intra-observer reliability studies showed no differences between
      echocardiographers on serial examinations. EF improved equally in the two groups.
      There is no therapeutic difference in EF improvement between lisinopril and
      losartan over the one-year duration for treatment of boys with DMD-related CM.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01982695.

PMID- 24459613
TI  - Power outages, extreme events and health: a systematic review of the literature
      from 2011-2012.
AB  - Background Extreme events (e.g. flooding) threaten critical infrastructure
      including power supplies. Many interlinked systems in the modern world depend on
      a reliable power supply to function effectively. The health sector is no
      exception, but the impact of power outages on health is poorly understood.
      Greater understanding is essential so that adverse health impacts can be
      prevented and/or mitigated. Methods We searched Medline, CINAHL and Scopus for
      papers about the health impacts of power outages during extreme events published
      in 2011-2012. A thematic analysis was undertaken on the extracted information.
      The Public Health England Extreme Events Bulletins between 01/01/2013 -
      31/03/2013 were used to identify extreme events that led to power outages during
      this three-month period. Results We identified 20 relevant articles. Power
      outages were found to impact health at many levels within diverse settings.
      Recurrent themes included the difficulties of accessing healthcare, maintaining
      frontline services and the challenges of community healthcare. We identified 52
      power outages in 19 countries that were the direct consequence of extreme events
      during the first three months of 2013. Conclusions To our knowledge, this is the
      first review of the health impacts of power outages. We found the current
      evidence and knowledge base to be poor. With scientific consensus predicting an
      increase in the frequency and magnitude of extreme events due to climate change,
      the gaps in knowledge need to be addressed in order to mitigate the impact of
      power outages on global health. 

PMID- 24459614
TI  - Characterization of Striatal Neuronal Loss and Atrophy in the R6/2 Mouse Model of
      Huntington's Disease.
AB  - Striatal neuronal degeneration and loss is an important feature of human
      Huntington's disease (HD). R6/2 HD mice recapitulate many features of human HD
      including striatal atrophy. While striatal neuronal atrophy and loss is reported
      in R6/2 HD mice the degree of neuronal loss and the characteristics of cell body
      atrophy are unclear. We used stereological approaches to estimate whole striatal
      neuronal numbers and characterize changes in striatal neuronal size distribution.
      R6/2 HD mice had ~126000 fewer neurons per striatum (~12% decline) at 12 weeks of
      age than wild-type litter-mates; differences were not present at 5 weeks.
      Analysis of striatal neuronal numbers per cell body size category revealed
      declines in neuron numbers in the size ranges 550-1050 um3 suggesting that larger
      striatal neurons are more susceptible to atrophy or loss in late stages of
      disease. R6/2 HD mice have a striatal neuronal loss phenotype. As striatal
      neuronal loss in human HD is dramatic, neuronal loss in R6/2 striatum provides an
      important late-stage outcome measure for study of disease modifying
      interventions. 

PMID- 24459615
TI  - Isolated Chorea Associated with LGI1 Antibody.
AB  - BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) antibody produces a syndrome
      of limbic encephalitis, hyponatremia, and facio-brachial dystonic seizures that
      is non-paraneoplastic and responsive to corticosteroids. Parkinsonism, tremor,
      and generalized chorea are rare manifestations of LGI1, but, when present,
      commonly accompany other signs of limbic encephalitis. CASE REPORT: We present a
      case of LGI1-related isolated chorea in a 53-year-old Japanese male. His chorea
      responded to high-dose steroids, suggesting a potential role for this synaptic
      antibody in triggering chorea. DISCUSSION: This case highlights a new treatable
      etiology of chorea.

PMID- 24459617
TI  - What's new in critical illness and injury science? Rationale drug usage - A long
      way ahead!

PMID- 24459618
TI  - A study of hand injury and emergency management in a developing country.
AB  - BACKGROUND: Injury to the underlying structures of the hand carries the potential
      for serious handicap. To reduce this risk, even the smallest hand injuries
      require proper medical care. AIMS: To assess wound healing, mobility, and the
      ability to perform normal essential function post-operatively in open hand
      injuries associated with fracture. MATERIALS AND METHODS: Thirty patients with 45
      metacarpal and phalangeal fractures of the hand were divided into three groups:
      Group 1 (n = 13) cases with single fractures of hand, excluding thumb; Group 2 (n
      = 9) cases with multiple fracture of hand, excluding thumb; Group 3 (n = 8) cases
      with fractures involving thumb and first metacarpal. Tendon injuries were
      repaired. For fractures, Kirschner wire fixation was done. In two cases with
      multiple fractures, Joshi's external support system (JESS) fixator was applied.
      Patients were followed up for 12 weeks. RESULTS: One patient with proximal
      phalangeal fracture developed extension lag. No stiffness was observed in any of
      the cases treated by intramedullary Kirschner wire fixation. No non-union or
      delayed union was observed following cross-wire fixation with two Kirschner
      wires. Two case of open fracture developed superficial infection. Two patients
      with multiple fractures developed angulation at fracture site after the Kirschner
      wires were removed 4 weeks postoperatively, and two cases of multiple fractures
      developed hypertrophic non-union. CONCLUSIONS: Delicate handling of tissues,
      preservation of gliding planes for tendons, prevention of infection, accurate
      reduction and fixation, and early and appropriate physiotherapy affect prognosis
      in case of hand injuries.

PMID- 24459619
TI  - Hospitalized injuries and deaths in a trauma unit in upper Egypt.
AB  - CONTEXT: It is predicted that injuries will be among the top 20 leading causes of
      death worldwide by 2030. In Egypt, injuries burden is significant as it was the
      fifth leading cause of death in 2004. Also, it's considered as a hidden epidemic
      due to under-reporting. AIMS: To identify the patterns of hospitalized injury
      cases at Trauma Unit in Assiut University Hospitals and to provide an indication
      about who are at increased risk of hospitalization or death due to injury.
      SETTINGS AND DESIGN: A descriptive retrospective study. MATERIALS AND METHODS:
      Registered data of all hospitalized injuries from January 2002 to December 2009
      at Trauma Unit of Assiut University Hospitals in Upper Egypt were included.
      STATISTICAL ANALYSIS: Advanced statistical package for social sciences (SPSS)
      program version 16 (IBM Corporation - http://www.spss.com) was used for data
      analysis. Descriptive statistics and tests of significance were used. P value was
      considered statistically significant when it was less than 0.05 and highly
      significant when it was less than 0.001. RESULTS: Admitted cases of attended
      injuries were (31.8%). Most admissions were below the age of 30 years (58.4%).
      Male to female ratio was 3:1. Falls were the most common injuries (43.6%),
      followed by transport accidents (31.1%). More than half of deaths (56.4%) were
      due to transport accidents. Transport accidents, falls, interpersonal violence
      and gunshot injuries had an early ranking throughout the study period.
      CONCLUSION: Road traffic injuries, falls and violence are areas of priority in
      preventive strategies. Paying special attention for young adults is recommended.

PMID- 24459620
TI  - Evaluation of the new supraglottic airway S.A.L.T to aid blind orotracheal
      intubation: A pilot study.
AB  - BACKGROUND AND OBJECTIVE: Supraglottic Airway Laryngopharyngeal Tube (S.A.L.T) is
      a new airway gadget conceived as an effective device to facilitate blind oro
      tracheal intubation. Literature review showed no available clinical study on
      human subjects. The aim of our study was to evaluate S.A.L.T as an adjunct to
      blind oro-tracheal intubation. METHODS:  STUDY DESIGN: Single centre, Single
      group, Open label, Prospective, Interventional pilot study. STUDY GROUP: 30 adult
      patients of either sex belonging to ASA I and II, scheduled for elective surgery
      under General anaesthesia. Patients were pre-medicated with inj. Glycopyrrolate
      0.2 mg and inj. Midazolam 2 mg and induced with Inj. Propofol 2 mg/kg IV. After
      inj. Suxamethonium 1.5 mg/kg IV, S.A.L.T was inserted and a size 7.0 ID cuffed
      ETT was inserted through it immediately. The time period, from insertion of the
      S.A.L.T to the insertion of the ETT was noted. A successful intubation was
      defined as to insert SALT and intubate through it within 2 minutes irrespective
      of the number of attempts. Airway trauma, if any was recorded. RESULTS: Only 40%
      of the patients were successfully intubated [(20.4% to 59.6% with 95% confidence
      interval (CI)]. The mean number of attempts required for intubation was 1.4 +/-
      0.67 (CI - 0.99 to 1.8) and the mean time for intubation was 26.3 +/- 19.0
      seconds (CI - 14.3 to 38.4 sec). Mallampati class I had more success rate than
      class III (P < 0.05). No airway trauma was recorded. CONCLUSION: S.A.L.T shows
      limited usefulness as an adjunct for aided blind oro-tracheal intubation.

PMID- 24459621
TI  - Influence of non-surgical risk factors on anastomotic leakage after major
      gastrointestinal surgery: Audit from a tertiary care teaching institute.
AB  - CONTEXT: The occurence of anastomotic leakage after gastointestinal resection and
      anastomosis is associated with significant mortality and morbidity. AIMS: There
      is dearth of evidence in the literature on the influence of various non-surgical
      factors in causing anastomotic leakage although many studies have identified
      their possible role. MATERIALS AND METHODS: A retrospective audit of all the
      anastomotic leakages occurring between September 2009 and April 2012 in our
      institute was performed to identify the potential non-surgical factors that can
      influence anastomotic leakage. A total of 137 out of 1246 patients who developed
      anastmotic leak were analyzed. All the potential non-surgical causes of
      anastomotic leakage available in the literature were analyzed by univariate
      analysis and stepwise multiple logistic regression analysis was done after
      adjusting for the type of surgery. An intergroup comparison among the patients
      based on the type of surgery was also performed. RESULTS: THE FOLLOWING FACTORS
      WERE FOUND TO BE INDEPENDENTLY ASSOCIATED WITH INCREASED RISK OF ANASTOMOTIC
      LEAK: (1) albumin <3.5 g/dl, (2) anemia <8 g/dl, (3) hypotension (4) use of
      inotropes, and (5) blood transfusion. The majority of anastomotic leaks occurred
      after pancreatic surgeries followed by esophagectomies and occurred least after
      colonic resections. The risk for anastomotic leak was four times more in patients
      who required inotropic support in the perioperative period and three times more
      in patients who developed hypotension. CONCLUSIONS: Our study is the first
      retrospective audit to identify the influence of non-surgical factors for
      anastomotic leakage and the need for further observational studies in this
      direction.

PMID- 24459622
TI  - Drug utilization pattern in critical care unit in a tertiary care teaching
      hospital in India.
AB  - AIMS: The aim of this study is to evaluate the drug utilization pattern and
      pharmacoeconomic analysis in critical care unit (CCU). MATERIALS AND METHODS:
      Indoor case papers of patients admitted in CCU between January 2008 and December
      2010 were analyzed for demographic variables; indications; duration of CCU stay;
      proportion of common drugs used. Use of antimicrobials was evaluated based on the
      culture report and empirical regimen used. Defined daily dose (DDD)/100 bed-days
      were calculated. Various World Health Organization prescribing indicators were
      evaluated. Cost of drugs was calculated from Indian Drug Review (2010). RESULTS:
      A total of 397 cases were evaluated with a mean age of 44.62 years (95%
      confidence interval [CI]: 42.56-46.69). Average duration of CCU stay was 4.15
      days (95% CI: 3.79-4.51). The average number of drugs prescribed per patient was
      13.54 (95% CI: 13.05-14.04). Total drug utilization in terms of DDD/100 bed-days
      was 226.27. Metronidazole, cefotaxime, atropine, adrenaline, dopamine,
      dobutamine, deriphyllin, ranitidine, metoclopramide and furosemide were
      prescribed in more than 30% cases. Number of antimicrobials prescribed per
      patient was 2.50 (95% CI: 2.37-2.66). Cefotaxime + metronidazole (26.70%) were
      the most common empirical regimen used. Average cost of treatment per patient was
      Rs 3225.70 (95% CI: 2749.8-3701.6). Higher economic burden was noted among
      expired patients and admitted due to medical + surgical indication (P < 0.05).
      CONCLUSION: Poly-pharmacy and use of antimicrobials without culture report is a
      common problem in CCU.

PMID- 24459623
TI  - Injury to the diaphragm: Our experience in Union Head quarters Hospital.
AB  - BACKGROUND: Diaphragmatic injury is a global diagnostic and therapeutic
      challenge. OBJECTIVES: The study was to identify the variations in the risk
      factors, diagnosis, management, and outcome between blunt and penetrating
      injuries of the diaphragm. MATERIALS AND METHODS: A prospective study was
      conducted on patients who were diagnosed with injury to diaphragm during
      preoperative, intraoperative, or postmortem period. The risk correlates and the
      trail of events following injury, interventions, and outcomes were studied.
      RESULTS: Of the 25 cases, blunt injury was experienced by 10. Road traffic injury
      was the most common cause in blunt trauma and assault with knife in penetrating
      trauma. Acute presentation was the most common mechanism. X-rays were positive in
      52% cases. The most common reason for false negative X-rays was massive
      effusion/hemothorax. Computed tomography (CT) improved the positivity rate to
      62.5%. A total of 25% of diaphragmatic injuries were diagnosed during surgery for
      hemodynamic instability irrespective of initial X-rays findings. Laprotomy alone
      was sufficient in majority of cases. The defects were largely in the left side;
      mean defect size was more in blunt trauma. Associated injuries were noted in 92%.
      Stomach was most affected in penetrating injuries and spleen in blunt trauma.
      Empeyma was the most common morbidity. Mortality rate of 13% in penetrating
      injury was far lower than 60% in blunt injury. Mean Injury Severity Score (ISS)
      was significantly related to the fatal outcomes irrespective of mechanism.
      Diagnostic laparoscopy for asymptomatic low velocity junctional penetrating
      wounds revealed diaphragmatic injury in 20%. CONCLUSIONS: The incidence of
      multisystem injuries at our trauma center is on the rise. A high index of
      suspicion is needed for diagnosis of diaphragmatic injury. The need for thorough
      exploratory laprotomy is essential. In resource stretched setting like ours, the
      need for routine diagnostic laparoscopy in asymptomatic junctional wounds has to
      be validated further.

PMID- 24459625
TI  - Trauma during pregnancy in a Nigerian setting: Patterns of presentation and
      pregnancy outcome.
AB  - CONTEXT: Trauma is an important health concern during pregnancy in developing
      nations though it is under-reported. AIMS: The aim of this study was to determine
      the patterns of presentation and feto- maternal outcomes of trauma during
      pregnancy in a Nigerian setting. SETTINGS AND DESIGN: A hospital-based
      retrospective analysis of database of entire patient population who presented in
      Ebonyi State University Teaching Hospital, Abakaliki, with trauma during
      pregnancy. MATERIALS AND METHODS: The data on demographics, obstetrics, and
      injury characteristic in addition to the outcome of all injured pregnant women
      hospitalized from January 2002 to December 2010 were analyzed. STATISTICAL
      ANALYSIS: SPSS version 16 and quantitative skills software SISA were used in data
      analysis. RESULTS: Trauma-necessitated hospitalization in 12 per 1000 pregnant
      women admitted in antenatal ward and was a complication of pregnancy in 4.7 per
      1000 live birth in the hospital. Physical assault was the predominant causative
      factor and accounted for 46% of injuries whereas road traffic accident
      (motorcycle injury related in over 80%) was involved in 30.2% of the patients.
      The parity of the patients was significantly related to the trimester of
      pregnancy at the time of injury - 73% of grand-multiparae and about 60% of
      primigravida involved presented with injury in the 3(rd) and 2(nd) trimester,
      respectively (P < 0.017). Preterm delivery (7.9%), abruptio placentae (4.8%), and
      stillbirth (4.8%) were common obstetric complications observed. Maternal
      mortality of 1.6% and fetal loss of 7.9% were associated with trauma.
      CONCLUSIONS: Injury prevention measures during pregnancy deserve a place in any
      policy response aimed at reducing feto-maternal morbidity and mortality in
      developing countries.

PMID- 24459626
TI  - Use of dexmedetomidine to facilitate non-invasive ventilation.
AB  - Patients with chronic obstructive pulmonary disease and congestive heart failure
      exacerbations, as well as pneumonia benefit from the use of non-invasive
      ventilation (NIV), due to increased patient comfort and a reduced incidence of
      ventilator-associated pneumonia. However, some patients do not tolerate NIV due
      to anxiety or agitation, and traditionally physicians have withheld sedation from
      these patients due to concerns of loss of airway protection and respiratory
      depression. We report our recent experience with a 91-year-old female who
      received NIV for acute respiratory distress secondary to pneumonia. The duration
      of NIV was a total time period of 86 h, using the bilevel positive airway
      pressure mode via a full face mask. The patient was initially agitated with the
      NIV, but with the addition of the dexmedetomidine, she tolerated it well. The
      dexmedetomidine was administered without a loading dose, as a continuous infusion
      ranging from 0.2 to 0.5 mcg/kg/hr, titrated to a Ramsey score of three. This case
      illustrates the safe use of dexmedetomidine to facilitate NIV, and improve
      compliance, which may reduce ICU length of stay. 

PMID- 24459624
TI  - Evaluation of tracheal cuff pressure variation in spontaneously breathing
      patients.
AB  - BACKGROUND: Most of the studies referring cuff tubes' issues were conducted on
      intubated patients. Not much is known about the cuff pressure performance in
      chronically tracheostomized patients disconnected from mechanical ventilation.
      OBJECTIVE: To evaluate cuff pressure (CP) variation in tracheostomized,
      spontaneously breathing patients in a weaning rehabilitation center. MATERIALS
      AND METHODS: Experimental setup to test instruments in vitro, in which the gauge
      (TRACOE) performance at different pressure levels was evaluated in six
      tracheostomy tubes, and a clinical setupin which CP variation over 24 h, every 4
      h, and for 6 days was measured in 35 chronically tracheostomized clinically
      stable, patients who had been disconnected from mechanical ventilation for at
      least 72 h. The following data were recorded: Tube brand, type, and size; date of
      the tube placed; the patient's body position; the position of the head; axillary
      temperature; pulse and respiration rates; blood pressure; and pulse oximetry.
      RESULTS: In vitro difference between the initial pressure (IP) and measured
      pressure (MP) was statistically significant (P < 0.05). The difference between
      the IP and MP was significant when selecting for various tube brands (P < 0.05).
      In the clinical set-up, 207 measurements were performed and the CP was >30 cm H2O
      in 6.28% of the recordings, 20-30 cm H2O in 42.0% of the recordings, and <20 cm
      H2O in 51.69% of the recordings. CONCLUSION: The systematic CP measurement in
      chronically tracheostomized, spontaneously breathing patients showed high
      variability, which was independent of tube brand, size, type, or time of
      placement. Consequently, measurements should be made more frequently.

PMID- 24459627
TI  - Esophageal perforation following cervical spine surgery: A review with
      considerations in airway management.
AB  - Anterior cervical discectomy and fusion (ACDF) is a commonly performed surgery
      for the treatment of spondylosis, radiculopathy, myelopathy, and trauma to the
      cervical spine. Esophageal perforation is a rare yet serious complication
      following ACDF with an incidence of 0.02 to 1.52%. We describe a case of a 24
      year-old man who underwent ACDF and corpectomy following a motor vehicle accident
      who subsequently developed delayed onset esophageal perforation requiring
      surgical intervention. We believe that the detailed review of the surgical
      management of esophageal perforation following cervical spine surgery will
      provide a deeper understanding for the Intensivist in regards to postoperative
      airway management in these types of patients. Careful extubation over a soft
      flexible exchange catheter should take place to help reduce the risk of
      perforation in the event reintubation is required. 

PMID- 24459628
TI  - Acute lung injury following the use of granulocyte-macrophage colony-stimulating
      factor.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic
      growth factor with immunostimulatory effects that include the activation and
      priming of neutrophils. Neutrophils are an important part of the human immune
      system, yet they have been implicated in the pathogenesis of acute lung injury
      (ALI). GM-CSF has been found to increase the amount of activated neutrophils
      recruited to the lung tissue as well as to increase the life span of neutrophils
      leading to substantial lung tissue injury and the development of ALI. While,
      there have been few cases reported of ALI following GM-CSF, the experience
      reported here is the first of ALI subsequent to local administration of GM-CSF in
      a patient with significant pulmonary comorbidities. 

PMID- 24459629
TI  - An iatrogenic metabolic encephalopathy in a nonagenarian: The dilemma of a
      critical miss as a possible social dismissal.
AB  - Here we posit for discussion the example of a reversible metabolic encephalopthy
      in a very elderly male that was missed clinically. A metabolic encephalopathy in
      extrememly elderly patients may be confused with delerium or inattention. A
      reversible cause of cognative dysfunction in the aged may be missed by
      practitioners because the aged may be assumed to have some level of impaired
      cognition; this may lead to a "social dismissal" of mental status changes. We
      highlight the need for engaged physicians in the care of the aged and vigilance
      against a professional bias toward the elderly patient that is dismissive. 

PMID- 24459630
TI  - Ruptured rudimentary horn pregnancy misdiagnosed as ruptured pseudo aneurysm
      internal iliac artery.

PMID- 24459631
TI  - Post-traumatic perineal necrotizing fasciitis.

PMID- 24459632
TI  - Outcome for tracheostomized patients who requiring prolonged stay in intensive
      care unit.

PMID- 24459633
TI  - Patient care delays due to scene safety.

PMID- 24459634
TI  - The potential and hurdles of targeted alpha therapy - clinical trials and beyond.
AB  - This article presents a general discussion on what has been achieved so far and
      on the possible future developments of targeted alpha (alpha)-particle therapy
      (TAT). Clinical applications and potential benefits of TAT are addressed as well
      as the drawbacks, such as the limited availability of relevant radionuclides.
      Alpha-particles have a particular advantage in targeted therapy because of their
      high potency and specificity. These features are due to their densely ionizing
      track structure and short path length. The most important consequence, and the
      major difference compared with the more widely used beta(-)-particle emitters, is
      that single targeted cancer cells can be killed by self-irradiation with alpha
      particles. Several clinical trials on TAT have been reported, completed, or are
      on-going: four using (213)Bi, two with (211)At, two with (225)Ac, and one with
      (212)Pb/(212)Bi. Important and conceptual proof-of-principle of the therapeutic
      advantages of alpha-particle therapy has come from clinical studies with (223)Ra
      dichloride therapy, showing clear benefits in castration-resistant prostate
      cancer. 

PMID- 24459636
TI  - Surgical Approaches for Stage IVA Thymic Epithelial Tumors.
AB  - Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can
      metastasize to the pleural space (stage IVA). Complete surgical resection remains
      the backbone of therapy for patients with early stage TET, however, the role of
      surgery in the management of patients with stage IVA disease is not fully
      defined. Published reports in this regard are mainly small, retrospective, and
      uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural
      disease include metastasectomy, extrapleural pneumonectomy, and
      metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The
      choice of the most appropriate surgical strategy needs to be individualized
      according to the quantity and location of disease, the patient's overall
      condition, as well as operator and institutional expertise. In the majority of
      cases, metastasectomy of pleural implants will be sufficient to achieve a
      complete resection. The available literature suggests that in selected patients
      with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete
      resection is a viable treatment option that can be associated with long-term
      survival. 

PMID- 24459635
TI  - Post-Synthetic Regulation of HS Structure: The Yin and Yang of the Sulfs in
      Cancer.
AB  - Heparan sulfate (HS) is a complex polysaccharide that takes part in most major
      cellular processes, through its ability to bind and modulate a very large array
      of proteins. These interactions involve saccharide domains of specific sulfation
      pattern (S-domains), the assembly of which is tightly orchestrated by a highly
      regulated biosynthesis machinery. Another level of structural control does also
      take place at the cell surface, where degrading enzymes further modify HS post
      synthetically. Amongst them are the Sulfs, a family of extracellular sulfatases
      (two isoforms in human) that catalyze the specific 6-O-desulfation of HS. By
      targeting HS functional sulfated domains, Sulfs dramatically alter its ligand
      binding properties, thereby modulating a broad range of signaling pathways.
      Consequently, Sulfs play major roles during development, as well as in tissue
      homeostasis and repair. Sulfs have also been associated with many pathologies
      including cancer, but despite increasing interest, the role of Sulfs in tumor
      development still remains unclear. Studies have been hindered by a poor
      understanding of the Sulf enzymatic activities and conflicting data have shown
      either anti-oncogenic or tumor-promoting effects of these enzymes, depending on
      the tumor models analyzed. These opposite effects clearly illustrate the fine
      tuning of HS functions by the Sulfs, and the need to clarify the mechanisms
      involved. In this review, we will detail the present knowledge on the structural
      and functional properties of the Sulfs, with a special focus on their implication
      during tumor progression. Finally, we will discuss attempts and perspectives of
      using the Sulfs as a biomarker of cancer prognosis and diagnostic and as a target
      for anti-cancer therapies. 

PMID- 24459638
TI  - Acute-on-chronic liver failure.
AB  - Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct
      disease entity encompassing an acute deterioration of liver function in patients
      with chronic liver disease. Although there are no widely accepted diagnostic
      criteria for ACLF, the Asia.Pacific Association for the Study of the Liver
      (APASL) and the American Association for the Study of Liver Disease and the
      European Association for the Study of the Liver (AASLD/EASL) consensus
      definitions are commonly used. It is obvious that the APASL and the AASLD/EASL
      definitions are based on fundamentally different features. Two different
      definitions in two different parts of the world hamper the comparability of
      studies. Recently, the EASL-Chronic Liver Failure Consortium proposed new
      diagnostic criteria for ACLF based on analyses of patients with organ failure.
      There are areas of uncertainty in defining ACLF, such as heterogeneity of ACLF,
      ambiguity in qualifying underlying liver disease, argument for infection or
      sepsis as a precipitating event, etc. Although the exact pathogenesis of ACLF
      remains to be elucidated, alteration of host response to injury, infection, and
      unregulated inflammation play important roles. The predisposition,
      infection/inflammation, response, organ failure (PIRO) concept used for sepsis
      might be useful in describing the pathophysiology and clinical categories for
      ACLF. Treatment strategies are limited to organ support but better understanding
      of the pathophysiology is likely to lead to discovery of novel biomarkers and
      therapeutic strategies in the future. 

PMID- 24459639
TI  - The MR imaging diagnosis of liver diseases using gadoxetic acid: emphasis on
      hepatobiliary phase.
AB  - Hepatocyte specific contrast agents including gadoxetic acid and gadobenate
      dimeglumine are very useful to diagnose various benign and malignant focal
      hepatic lesions and even helpful to estimate hepatic functional reservoir. The
      far delayed phase image referred to as the hepatobiliary phase makes the
      sensitivity of detection for malignant focal hepatic lesions increased, but
      specificity of malignant diseases, including hepatocellular carcinoma, metastasis
      and cholangiocarcinoma, characterization remained to be undetermined. 

PMID- 24459640
TI  - Liver stiffness measurement: is it a non-invasive substitution for HVPG?

PMID- 24459637
TI  - KASL clinical practice guidelines: management of nonalcoholic fatty liver
      disease.

PMID- 24459641
TI  - The usefulness of non-invasive liver stiffness measurements in predicting
      clinically significant portal hypertension in cirrhotic patients: Korean data.
AB  - BACKGROUND/AIMS: Liver stiffness measurement (LSM) has been proposed as a non
      invasive method for estimating the severity of fibrosis and the complications of
      cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold
      standard for assessing the presence of portal hypertension, but its invasiveness
      limits its clinical application. In this study we evaluated the relationship
      between LSM and HVPG, and the predictive value of LSM for clinically significant
      portal hypertension (CSPH) and severe portal hypertension in cirrhosis. METHODS:
      LSM was performed with transient elastography in 59 consecutive cirrhotic
      patients who underwent hemodynamic HVPG investigations. CSPH and severe portal
      hypertension were defined as HVPG >=10 and >=12 mmHg, respectively. Linear
      regression analysis was performed to evaluate the relationship between LSM and
      HVPG. Diagnostic values were analyzed based on receiver operating characteristic
      (ROC) curves. RESULTS: A strong positive correlation between LSM and HVPG was
      observed in the overall population (r(2)=0.496, P<0.0001). The area under the ROC
      curve (AUROC) for the prediction of CSPH (HVPG >=10 mmHg) was 0.851, and the
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%,
      86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal
      hypertension (HVPG >=12 mmHg) was 0.877, and the sensitivity, specificity, PPV,
      and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%,
      respectively. CONCLUSIONS: LSM exhibited a significant correlation with HVPG in
      patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH
      and severe portal hypertension in Korean patients with liver cirrhosis.

PMID- 24459642
TI  - Predicting factors of present hepatitis C virus infection among patients positive
      for the hepatitis C virus antibody.
AB  - BACKGROUND/AIMS: To identify the predicting factors of present hepatitis C virus
      (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV).
      METHODS: We analyzed patients who showed positive enzyme immunoassay (EIA)
      results and performed an HCV RNA test as a confirmatory test at Kyung Hee
      University Hospital at Gangdong from June 2006 to July 2012. The features
      distinguishing the groups with positive and negative HCV RNA results were
      reviewed. RESULTS: In total, 490 patients were included. The results of the HCV
      RNA test were positive and negative in 228 and 262 patients, respectively. The
      index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin
      time international normalized ratio, albumin and alanine transaminase (ALT)
      levels differed significantly between the two groups. On multivariable analysis,
      an index value of anti-HCV >10 [odds ratio (OR)=397.27, P<0.001), ALT >40 IU/L
      (OR=3.64, P=0.001), and albumin <3.8 g/dL (OR=2.66, P=0.014) were related to
      present HCV infection. CONCLUSIONS: Although EIA is not a quantitative test,
      considering the anti-HCV titer with ALT and albumin levels may be helpful in
      predicting present of HCV infection.

PMID- 24459643
TI  - The levels of liver enzymes and atypical lymphocytes are higher in youth patients
      with infectious mononucleosis than in preschool children.
AB  - BACKGROUND/AIMS: Infectious mononucleosis (IM) is the clinical presentation of
      primary infection with Epstein-Barr virus. Although the literature contains a
      massive amount of information on IM, most of this is related specifically to only
      children or adults separately. In order to distinguish any differences between
      preschool children and youth patients, we retrospectively analyzed their
      demographic and clinical features. METHODS: Records of patients hospitalized from
      December 2001 to September 2011 with a diagnosis of IM were retrieved from Peking
      University First Hospital, which is a tertiary teaching hospital in Beijing. The
      demographic data and clinical characteristics were collected. RESULTS: IM was
      diagnosed in 287 patients during this 10-year period, with incidence peaks among
      preschool children (<=7 years old, 130/287, 45.3%) and youth patients (>15 and
      <24 years old, 101/287, 35.2%). Although the complaints at admission did not
      differ between these two patient groups, the incidence of clinical signs
      (tonsillopharyngitis, lymphadenopathy, hepatomegaly, and edema of the eyelids)
      was much higher in preschool children. The incidence of liver lesion and
      percentage of atypical lymphocytes were significantly higher in the youth group
      (P<0.001), and the average hospital stay was longer in this group. Pneumonia was
      the most common complication, and there was no case of mortality. CONCLUSIONS:
      The incidence of IM peaks among preschool children and youth patients in Beijing,
      China. The levels of liver enzymes and atypical lymphocytes increase with age.

PMID- 24459644
TI  - Ultrasonographic scoring system score versus liver stiffness measurement in
      prediction of cirrhosis.
AB  - BACKGROUND/AIMS: We compared the cirrhosis-prediction accuracy of an
      ultrasonographic scoring system (USSS) combining six representative sonographic
      indices with that of liver stiffness measurement (LSM) by transient elastography,
      and prospectively investigated the correlation between the USSS score and LSM in
      predicting cirrhosis. METHODS: Two hundred and thirty patients with chronic liver
      diseases (187 men, 43 women; age, 50.4+/-9.5 y, mean+/-SD) were enrolled in this
      prospective study. The USSS produces a combined score for nodularity of the liver
      surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen
      size, splenic vein diameter, and abnormality of the hepatic vein waveform. The
      correlations of the USSS score and LSM with that of a pathological liver biopsy
      (METAVIR scoring system: F0-F4) were evaluated. RESULTS: The mean USSS score and
      LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt
      cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change
      without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating
      characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849
      and 0.729, respectively. On the basis of ROC curves, criteria of USSS >=6: LSM
      >=17.4 had a sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%,
      74.6%:51.9% and 0.83:0.73, respectively, in predicting F4. CONCLUSIONS: The
      results indicate that this USSS has comparable efficacy to LSM in the diagnosis
      of cirrhosis.

PMID- 24459645
TI  - Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir
      resistance mutations in chronic hepatitis B.
AB  - BACKGROUND/AIMS: Molecular diagnostic methods have enabled the rapid diagnosis of
      drug-resistant mutations in hepatitis B virus (HBV) and have reduced both
      unnecessary therapeutic interventions and medical costs. In this study we
      evaluated the analytical and clinical performances of the HepB Typer-Entecavir
      kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations.
      METHODS: The HepB Typer-Entecavir kit was evaluated for its limit of detection,
      interference, cross-reactivity, and precision using HBV reference standards made
      by diluting high-titer viral stocks in HBV-negative human serum. The performance
      of the HepB Typer-Entecavir kit for detecting mutations related to entecavir
      resistance was compared with direct sequencing for 396 clinical samples from 108
      patients. RESULTS: Using the reference standards, the detection limit of the HepB
      Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity
      was observed, and elevated levels of various interfering substances did not
      adversely affect its analytical performance. The precision test conducted by
      repetitive analysis of 2,400 replicates with reference standards at various
      concentrations showed 99.9% agreement (2398/2400). The overall concordance rate
      between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical
      samples was 99.5%. CONCLUSIONS: The HepB Typer-Entecavir kit showed high
      reliability and precision, and comparable sensitivity and specificity for
      detecting mutant virus populations in reference and clinical samples in
      comparison with direct sequencing. Therefore, this assay would be clinically
      useful in the diagnosis of entecavir-resistance-associated mutations in chronic
      hepatitis B.

PMID- 24459646
TI  - HBsAg level and clinical course in patients with chronic hepatitis B treated with
      nucleoside analogue: five years of follow-up data.
AB  - BACKGROUND/AIMS: Quantification of the hepatitis B surface antigen (HBsAg) is
      increasingly used to determine the treatment response in patients with chronic
      hepatitis B (CHB). However, there are limited data about the clinical
      implications of Quantification of HBsAg long-term nucleoside analogue treatment
      for CHB. We investigated the clinical correlation between HBsAg level and
      clinical course in patients with CHB who are treated long-term with nucleoside
      analogues. METHODS: Patients with CHB who started lamivudine or entecavir
      monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at
      6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between
      the groups according to the presence or absence of a virological response (VR)
      and resistance. RESULTS: Forty-eight patients were analyzed. There was no
      definite reduction in HBsAg level during the early period of treatment;
      differences in HBsAg levels between baseline and each time point were significant
      only at 5 years (P=0.028). In a subgroup analysis, this difference was
      significant only in non-resistant patients at 5 years (P=0.041). CONCLUSIONS:
      There was no definite decrease in the HBsAg level during the early period of
      nucleoside analogue treatment, with long-term treatment being required to observe
      a significant reduction.

PMID- 24459647
TI  - Severe ischemic bowel necrosis caused by terlipressin during treatment of
      hepatorenal syndrome.
AB  - Terlipressin is a vasopressin analogue that is widely used in the treatment of
      hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic
      vessels, terlipressin has a lower incidence of severe ischemic complications than
      does vasopressin. However, it can still lead to serious complications such as
      myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case
      of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with
      terlipressin. Although the patient received bowel resection, death occurred due
      to ongoing hypotension and metabolic acidosis. Attention should be paid to
      patients complaining of abdominal pain during treatment with terlipressin. 

PMID- 24459648
TI  - Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in
      type I diabetes mellitus.
AB  - Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation
      in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are
      nonspecific, and include abdominal discomfort, mild hepatomegaly, and
      transaminase elevation. In this report we describe three cases of patients
      presenting serum transaminase elevation and hepatomegaly with a history of poorly
      controlled type I DM. All of the cases showed sudden elevation of transaminase to
      more than 30 times the upper normal range (like in acute hepatitis) followed by
      sustained fluctuation (like in relapsing hepatitis). However, the patients did
      not show any symptom or sign of acute hepatitis. We therefore performed a liver
      biopsy to confirm the cause of liver enzyme elevation, which revealed GH.
      Clinicians should be aware of GH so as to prevent diagnostic delay and
      misdiagnosis, and have sufficient insight into GH; this will be aided by the
      present report of three cases along with a literature review. 

PMID- 24459649
TI  - A sclerosing hemangioma of the liver.

PMID- 24459650
TI  - Hepatic abscess mimicking hepatocellular carcinoma in a patient with alcoholic
      liver disease.

PMID- 24459651
TI  - The non-surgical treatment of peyronie disease: 2013 update.
AB  - Peyronie disease is a common cause of penile deformity and sexual dysfunction.
      Although surgery is regarded as the definitive management for this condition,
      there are many medical and minimally invasive therapies available, with widely
      varying efficacy reported in the literature. The purpose of this review is to
      describe the current state-of-the-art for each of the most commonly used as well
      as several developing non-surgical treatments. Further, we hope to offer
      perspectives that will aid practitioners in deciding among these treatments that
      are either already in use or have the potential to be used as alternatives to
      surgery in the management of this frustrating disease. 

PMID- 24459652
TI  - Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH) and
      LUTS/BPH with Erectile Dysfunction in Asian Men: A Systematic Review Focusing on
      Tadalafil.
AB  - This review assesses lower urinary tract symptoms (LUTS) due to benign prostatic
      hyperplasia (BPH) with or without erectile dysfunction (ED) and related therapies
      focusing on tadalafil. A literature search was obtained and reviewed for the
      epidemiology, treatment therapies, pathophysiology, and efficacy and safety of
      phosphodiesterase type 5 inhibitor (PDE5i) tadalafil in patients with LUTS/BPH.
      Approximately 42% of men aged 51 to 60 years have BPH. Approximately 90% of men
      aged 45 to 80 years have LUTS. Occurrence of LUTS increases with age for almost
      all racial/ethnic groups (range, 32% to 56%) with prevalence of LUTS highest
      among Hispanic men, then Blacks, Caucasians, and Asians. There is an independent
      relationship with LUTS/BPH and ED, with approximately 70% of men with LUTS/BPH
      having ED with severity of one disease often correlating with the other. The
      European Urological Association guidelines include the use of the PDE5i
      tadalafil. Tadalafil is the only therapy recommended for treatment of co-existing
      BPH and ED, while other therapies have unwanted ED side effects. The mode of
      action of tadalafil may involve different areas of the lower urinary tract such
      as smooth muscle cell relaxation in the bladder neck, prostate, and urethra, but
      there may also be resulting modulation of the afferent nerve activity. Tadalafil
      (5 mg) in Asian men with LUTS/BPH, similar to global studies, is efficacious and
      safe. Tadalafil (5 mg) improves co-existing LUTS/BPH and ED, independently. Men
      with LUTS/BPH likely also have ED. Asian men with LUTS/BPH have similar incidence
      rates, co-existing ED, comorbid diseases, and risks as non-Asian men. Tadalafil
      can improve co-existing LUTS/BPH and ED. 

PMID- 24459653
TI  - Low-intensity shock wave therapy and its application to erectile dysfunction.
AB  - Although phosphodiesterase type 5 inhibitors (PDE5Is) are a revolution in the
      treatment of erectile dysfunction (ED) and have been marketed since 1998, they
      cannot restore pathological changes in the penis. Low-energy shock wave therapy
      (LESWT) has been developed for treating ED, and clinical studies have shown that
      LESWT has the potential to affect PDE5I non-responders with ED with few adverse
      effects. Animal studies have shown that LESWT significantly improves penile
      hemodynamics and restores pathological changes in the penis of diabetic ED animal
      models. Although the mechanisms remain to be investigated, recent studies have
      reported that LESWT could partially restore corpus cavernosum fibromuscular
      pathological changes, endothelial dysfunction, and peripheral neuropathy. LESWT
      could be a novel modality for treating ED, and particularly PDE5I non-responders
      with organic ED, in the near future. However, further extensive evidence-based
      basic and clinical studies are needed. This review intends to summarize the
      scientific background underlying the effect of LESWT on ED. 

PMID- 24459654
TI  - Can the mean platelet volume be a risk factor for vasculogenic erectile
      dysfunction?
AB  - PURPOSE: The mean platelet volume (MPV) is a marker of the platelet activity and
      is reported to increase in vascular diseases. We aimed to investigate the
      association between MPV and vasculogenic erectile dysfunction (ED). MATERIALS AND
      METHODS: MPV and platelet (PLT) levels were measured in 50 cases of ED and 40
      healthy controls. The diagnosis of vasculogenic ED was based on a detailed sexual
      history, physical examination, laboratory assessment, and color Doppler
      ultrasonography. The results are given as mean+/-standard deviation of the mean.
      RESULTS: The mean ages of the patient and the control groups were 53.70+/-12.39
      years (range 24~77 years) and 53.85+/-9.5 years (range 30~73 years), respectively
      (p=0.947). The MPV and PLT values were significantly higher in the patients with
      ED than those of the controls (7.49+/-1.4), (6.85+/-1.2), (262.97+/-68),
      (252.89+/-82) respectively, p<0.001). However, the MPV values were not
      statistically significantly different in the patients with severe ED according to
      the International Index of Erectile Function than in those with mild ED, p>0.05),
      and there was no correlation between MPV and either age of patients (p=0.905) or
      duration of ED (p=0.583). CONCLUSIONS: The platelet count and MPV was detected to
      be increased in patients with vasculogenic ED. This finding suggests a role for
      platelets in the pathogenesis of vascular complications and that the MPV would be
      useful in monitoring disease progression.

PMID- 24459655
TI  - Dichotomous estimation of prostate volume: a diagnostic study of the accuracy of
      the digital rectal examination.
AB  - PURPOSE: To assess the diagnostic reliability of a dichotomous digital rectal
      examination (DRE) tool in assessing prostate volume (PV) compared to gold
      standard transrectal ultrasound (TRUS) volume measurement. MATERIALS AND METHODS:
      Male patients presenting to a single tertiary referral centre urology practice
      requiring TRUS were prospectively recruited between January 2010 and August 2011.
      Size was estimated by DRE immediately prior to TRUS measurement. DRE measurements
      were classed into four groups: <30 mL , 30 to 49 mL, 50 to 99 mL and >100 mL. The
      primary outcomes were sensitivity, specificity, and the positive and negative
      likelihood ratios for a 30 mL cut-off. RESULTS: Three hundred and three patients
      were recruited to the study. The median age of the study group was 64.9 years. On
      TRUS analysis, 244 patients had a PV larger than 30 mL and 139 of them, larger
      than 50 mL. The median PV was 47 mL with a median International Prostate Symptom
      Score of 10 and prostatic specific antigen (PSA) of 5.7. When analysed for the
      ability to identify a gland larger than 30 mL, DRE had a high sensitivity and low
      negative likelihood ratio. The median PSA level (ng/L) for prostates measured by
      DRE with a 30 mL cut-off was significantly different with higher median PSA
      values for volumes larger than 30 mL. CONCLUSIONS: DRE is a reliable tool for
      dichotomous assessment of prostatic volumes above 30 mL and 50 mL. These results
      illustrate the value of re-examining the role of categorical DRE estimations in
      benign prostatic hyperplasia patients.

PMID- 24459656
TI  - Urologist's Practice Patterns Including Surgical Treatment in the Management of
      Premature Ejaculation: A Korean Nationwide Survey.
AB  - PURPOSE: According to previous studies, the prevalence of premature ejaculation
      (PE) in Korea ranges from 11.3% to 33%. However, the actual practice patterns in
      managing patients with PE is not well known. In this study, we have endeavored to
      determine how contemporary urologists in Korea manage patients with PE. MATERIALS
      AND METHODS: The e-mailing list was obtained from the Korean Urological
      Association Registry of Physicians. A specifically designed questionnaire was e
      mailed to the 2,421 urologists in Korea from May 2012 to August 2012. RESULTS:
      UROLOGISTS IN KOREA DIAGNOSED PE USING VARIOUS CRITERIA: the definition of the
      International Society for Sexual Medicine (63.4%), Diagnostic and Statistical
      Manual of Mental Disorders (43.8%), International Statistical Classification of
      Disease, 10th edition (61.7%), or perceptional self-diagnosis by the patient
      himself (23.5%). A brief self-administered questionnaire, the Premature
      Ejaculation Diagnostic Tool, was used by only 42.5% of the urologists. Selective
      serotonin reuptake inhibitor (SSRI) therapy was the main treatment modality
      (91.5%) for PE patients. 40.2% of the urologists used phosphodiesterase type 5
      inhibitors, 47.6% behavior therapy, and 53.7% local anesthetics. Further, 286
      (54.3%) urologists managed PE patients with a surgical modality such as selective
      dorsal neurotomy (SDN). CONCLUSIONS: A majority of Korean urologists diagnose PE
      by a multidimensional approach using various diagnostic tools. Most urologists
      believe that medical treatment with an SSRI is effective in the management of PE.
      At the same time, surgical treatment such as SDN also investigated as one of
      major treatment modality despite the lack of scientific evidence.

PMID- 24459657
TI  - The Association between Type of Work and Insulin Resistance and the Metabolic
      Syndrome in Middle-Aged Korean Men: Results from the Korean National Health and
      Nutrition Examination Survey IV (2007~2009).
AB  - PURPOSE: Type of work might be related to insulin resistance and the metabolic
      syndrome (MetS). However, scant data are available. We performed this study to
      investigate whether the prevalence of MetS and insulin resistance differed
      according to occupation in middle-aged men. MATERIALS AND METHODS: In all, 2,348
      men in their 40s~50s who had participated in the Korean National Health and
      Nutrition Examination Survey IV were included and were classified into two groups
      according to the type of work (manual worker vs. non-manual worker). Diagnosis of
      MetS required satisfying three or more of the National Cholesterol Education
      Program-Adult Treatment Panel III criteria. Fasting insulin, the glucose/insulin
      ratio (G/I ratio), and the homeostasis model assessment of insulin resistance
      (HOMA-IR) were used to estimate the insulin resistance. We used the Mann-Whitney
      test, chi(2) tests, multiple linear regression test, and logistic regression
      analyses to examine the relationships. RESULTS: Age was significantly higher in
      the manual worker group. Body mass index was significantly lower in the manual
      worker group. Rates of current smoking and frequent drinking were higher in the
      manual worker group. In terms of surrogate markers of insulin resistance, the age
      adjusted mean of fasting insulin, G/I ratio, and HOMA-IR indicated that lower
      insulin resistance was significantly related to manual work. After adjusting for
      age and other confounding factors, non-manual workers had a higher risk of the
      MetS than manual workers. The odds ratio in relation to MetS was significantly
      lower in the manual workers. CONCLUSIONS: MetS and impaired insulin resistance
      are significantly related to non-manual work in middle-aged Korean men.

PMID- 24459658
TI  - The effect of anthocyanin on the prostate in an andropause animal model: rapid
      prostatic cell death by apoptosis is partially prevented by anthocyanin
      supplementation.
AB  - PURPOSE: To evaluate the anti-apoptotic effect of the antioxidant reaction of
      anthocyanin on the prostate in an andropause animal model. MATERIALS AND METHODS:
      Sprague-Dawley rats were divided into three groups (n=12 in each): control (Group
      I), andropause (Group II), andropause treated with anthocyanin (Group III). For
      induction of andropause, Group II and III underwent bilateral orchiectomy. Group
      III was treated with daily oral anthocyanin (160 mg/kg) for 8 weeks. After 8
      weeks, the rats were sacrificed and their blood and prostates were examined
      pathohistologically and evaluated for oxidative stress and apoptosis. Oxidative
      stress was assessed by the activity of superoxide dismutase (SOD) and apoptosis
      in the prostate was identified by terminal deoxyribonucleotidyl transferase
      mediated dUTP-digoxigenin nick end-labelling assay. RESULTS: Group II showed
      markedly increased activity of SOD in serum over that observed in Group I,
      whereas the rats in Group III showed reduced oxidative stress compared to Group
      II. Despite no significant differences in prostate weight between Group II and
      III (p=0.078), the apoptotic index was significantly greater in Group II than
      Group I, and was significantly lesser in Group III than Group II. CONCLUSIONS: We
      suggest that the oxidative stress caused by low testosterone may be another
      inducer of apoptosis, and this apoptosis may partly contribute to the overall
      apoptosis of the prostate in the andropause animal model. Therefore, anthocyanin
      supplementation may contribute to preventing excessively rapid cell death by
      apoptosis in the prostate in an animal model of andropause.

PMID- 24459659
TI  - Expression of heat shock protein 27 in prostate cancer cell lines according to
      the extent of malignancy and doxazosin treatment.
AB  - PURPOSE: Heat shock protein 27 (HSP27) is known as the material that plays a role
      in apoptosis control in tumor and cell protection including the immune response,
      drug tolerance, and so on. In this study, HSP27 expression according to the
      prostate cancer malignancy level was evaluated, and HSP27 expression was also
      analyzed after inducing apoptosis by doxazosin treatment of the prostate cancer
      cell lines. MATERIALS AND METHODS: Reverse transcription polymerase chain
      reaction (RT-PCR) and immunofluorescence staining of the HSP27 was implemented by
      the culture of RWPE-1, LNCaP, androgen-independent human prostate cancer cells
      (PC-3), and TSU-Pr1 cell lines. Analysis was separately conducted in the control
      group, control vector group treated by dimethyl sulfoxide, and groups treated
      with 10 uM or 25 uM doxazosin. The expression of HSP27 in RT-PCR and
      immunofluorescence staining was observed and evaluated after conversion to
      numerical values. RESULTS: In the RT-PCR results, depending on the cell type,
      LNCaP, TSU-Pr1 showed the highest HSP27 expression followed by PC-3, LNCaP and
      RWPE-1 in sequence. After doxazosin treatment, the expression detected by RT-PCR
      was stronger at a 25-uM doxazosin concentration compared to that at a 10-uM
      concentration, and the result was similar by immunofluorescence staining.
      CONCLUSIONS: HSP27 expression increased depending on the prostate cancer cell
      line. This meant that HSP27 expression was related to the prostate cancer
      malignancy level. Additionally, the higher the treatment concentration in PC-3
      was, the higher the HSP27 expression was. This result showed that doxazosin
      induced apoptosis of prostate cancer.

PMID- 24459660
TI  - Preliminary report on the safety of a new herbal formula and its effect on sperm
      quality.
AB  - PURPOSE: Male infertility is a serious problem, and its prevalence has been
      increasing. Therefore, we investigated the safety of a new herbal formula and its
      effects on sperm quality. MATERIALS AND METHODS: An in vitro cytotoxicity test in
      TM3 Leydig cells was performed to evaluate cell viability after administration of
      five types of herbs separately and of a new herbal formula containing these five.
      An in vivo test in male mice was performed to evaluate the influence of the new
      herbal formula on the reproductive organs and sperm quality. After the 8- and 28
      day oral administration of the new herbal formula, the weights of the
      reproductive organs were measured and the sperm count and motility were
      evaluated. RESULTS: In the in vitro cytotoxicity test, less than 80% cell
      viability at concentrations of 500 mg/L and 1,000 mg/L of Rubus coreanus Miquel
      and Cuscuta chinensis Lam was observed. However, more than 80% cell viability was
      observed at all the tested concentrations of the new herbal formula. After the 8-
      and 28-day oral administration, there were no considerable changes in body
      weight. The weights of the testes, epididymis, and seminal vesicles after the 8-
      and 28-day oral administration were similar to those of the control. The sperm
      count and activity were significantly improved compared with those of the control
      group at 8 and 28 days after 100, 200, and 400 mg of oral administration.
      CONCLUSIONS: The safety of the new formula and its positive effect on the sperm
      quality were observed after the oral administration of the formula.

PMID- 24459661
TI  - A case of fibrous pseudotumor of the paratesticular region.
AB  - A 78-year-old male patient presented with an inguinoscrotal nodule that had
      lasted for 3 years. The patient reported a past medical history of hydrocele
      formation. The final diagnosis was fibrous pseudotumor of the paratesticular
      region, which was based on a histopathological examination and
      immunohistochemical findings. The aim of this case report is to spread awareness
      and recognition of neoplastic and non-neoplastic entities that occur in the
      paratesticular region. 

PMID- 24459662
TI  - An unusual presentation of crossed testicular ectopia as an incarcerated inguinal
      hernia.
AB  - Crossed testicular ectopia (CTE) is generally defined as both testes located in
      the same hemiscrotum and contralateral hydrocele with the absence of a testis.
      However, the initial presentation of CTE in an infant as an incarcerated inguinal
      hernia is extremely rare. We report on a 10-month-old infant with CTE, who
      visited the emergency room presenting with a left incarcerated inguinal hernia.
      After manual reduction for an incarcerated hernia and left inguinal herniorraphy,
      the left testis was fixed into the left hemiscrotum and right transseptal
      orchiopexy was performed. 

PMID- 24459663
TI  - A Case of Duplicated Vas Deferens Found Incidentally during Varicocelectomy.
AB  - Duplication of the vas deferens is a very rare congenital anomaly in which two
      vasa deferentia coexist within the spermatic cord. Duplication of the vas
      deferens can be found during herniorrhaphy, vasectomy, and varicocelectomy
      performed on the spermatic cord or around the spermatic cord. However, it is
      estimated that the incidence of duplication of the vas deferens is under-reported
      and under-recognized. Unless anomalies of the vas deferens such as duplication of
      the vas deferens are recognized by surgeons, it will be difficult to reduce vas
      deferens injuries and achieve a satisfactory surgical outcome. In addition, care
      should be taken in cases of duplication of the vas deferens because it can be
      complicated by non-testicular genitourinary anomalies. We report a case of
      duplication of the vas deferens discovered during routine varicocelectomy. 

PMID- 24459664
TI  - Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of
      Neuroblastoma.
AB  - Despite major advances in pediatric cancer research, there has been only modest
      progress in the survival of children with high risk neuroblastoma (NB) (HRNB).
      The long term survival rates of HRNB in the United States are still only 30-50%.
      Due to resistance that often develops during therapy, development of new
      effective strategies is essential to improve the survival and overcome the
      tendency of HRNB patients to relapse subsequent to initial treatment. Current
      chemotherapy regimens also have a serious limitation due to off target toxicity.
      In the present work, we evaluated the potential application of reconstituted high
      density lipoprotein (rHDL) containing fenretinide (FR) nanoparticles as a novel
      approach to current NB therapeutics. The characterization and stability studies
      of rHDL-FR nanoparticles showed small size (<40 nm) and high encapsulation
      efficiency. The cytotoxicity studies of free FR vs. rHDL/FR toward the NB cell
      lines SK-N-SH and SMS-KCNR showed 2.8- and 2-fold lower IC50 values for the rHDL
      encapsulated FR vs. free FR. More importantly, the IC50 value for retinal pigment
      epithelial cells (ARPE-19), a recipient of off target toxicity during FR therapy,
      was over 40 times higher for the rHDL/FR as compared to that of free FR. The
      overall improvement in in vitro selective therapeutic efficiency was thus about
      100-fold upon encapsulation of the drug into the rHDL nanoparticles. These
      studies support the potential value of this novel drug delivery platform for
      treating pediatric cancers in general, and NB in particular. 

PMID- 24459665
TI  - Psychosocial profile of bullies, victims, and bully-victims: a cross-sectional
      study.
AB  - While adverse conditions in a child's life do not excuse inappropriate behavior,
      they may cause emotional and behavioral problems that require treatment as a
      preventive measure to reduce the likelihood of bullying. We aimed to identify
      differences in the psychosocial profiles of adolescents who classified themselves
      as bullies, victims, or bully-victims. We performed a cross-sectional study in
      which data were collected between January 2009 and January 2010 from seven
      university-based clinics in a large metropolitan area with a predominantly
      Mexican-American population. We collected data on physical aggression among
      adolescents who self-categorized into the following groups: uninvolved, bullies,
      victims, and bully-victims. We determined the psychosocial profiles of the
      adolescents based on responses to the Youth Self Report (YSR) and parent's
      responses to the Child Behavior Checklist (CBCL). A one-way analysis of variance
      and multivariate regression analyses were performed to compare the various
      components of the psychosocial profiles among the groups. Our analysis of the
      CBCL and the YSR assessments identified differences between the uninvolved group
      and one or more of the other groups. No significant differences were observed
      among the bully, victim, and bully-victim groups based on the CBCL. We did find
      significant differences among those groups based on the YSR, however. Our results
      suggest that emotional and behavioral problems exist among bullies, victims, and
      bully-victims. Therefore, treatment should not focus only on the victims of
      bullying; treatment is equally important for the other groups (bullies and bully
      victims). Failure to adequately treat the underlying problems experienced by all
      three groups of individuals could allow the problems of bullying to continue. 

PMID- 24459666
TI  - Immobilization of bone morphogenetic protein on DOPA- or dopamine-treated
      titanium surfaces to enhance osseointegration.
AB  - Titanium was treated with 3,4-dihydroxy-L-phenylalanine (DOPA) or dopamine to
      immobilize bone morphogenetic protein-2 (BMP2), a biomolecule. DOPA and dopamine
      solutions turned into suspensions, and precipitates were produced at high pH.
      Both treatments produced a brown surface on titanium that was thicker at high pH
      than low pH. Dopamine produced a thicker layer than DOPA. The hydrophobicity of
      the surfaces increased after treatment with dopamine independent of pH.
      Furthermore, there were more amino groups in the layers formed at pH 8.5 than pH
      4.5 in both treatments. Dopamine treatment produced more amino groups in the
      layer than DOPA. BMP2 was immobilized on the treated surfaces via a coupling
      reaction using carbodiimide. More BMP2 was immobilized on surfaces treated at pH
      8.5 than pH 4.5 in both treatments. The immobilized BMP induced specific signal
      transduction and alkali phosphatase, a differentiation marker. Thus, the present
      study demonstrates that titanium treated with DOPA or dopamine can become
      bioactive via the surface immobilization of BMP2, which induces specific signal
      transduction. 

PMID- 24459667
TI  - Cadmium phytoremediation by Arundo donax L. from contaminated soil and water.
AB  - The potential of Arundo donax L. for phytoextraction of cadmium (Cd) from
      contaminated soil and water was probed. The plants were grown under greenhouse
      conditions in pots containing a nutrient solution or soil with increasing doses
      of Cd (0, 50, 100, 250, 500, 750, and 1000 MUg L(-1)) for 21 days. The growth and
      physiology of plants were evaluated at the end of the experiment. The maximum Cd
      content in root was 300 MUg g(-1) during hydroponics experiments over 230 MUg g(
      1) in soil experiment. Cd concentration in stem was 262 MUg g(-1) at 750 MUg L(
      1) supplied Cd in hydroponics over 191.2 MUg g(-1) at 1000 in soil experiment.
      The maximum Cd concentration in leaves from hydroponics was 187 MUg g(-1).
      Relatively low Cd uptake occurred during soil experiment with low translocation
      factor (TF) values. Both Bioaccumulation Factor (BF) and TF values for
      hydroponics were greater than 1. The IC50 values of ABTS and DPPH showed that
      both time and increasing Cd concentrations affected the production of
      antioxidants with lower half maximal inhibitory concentration (IC50) value on the
      21st days. A. donax showed better potential for Cd remediation of aquatic
      environments.

PMID- 24459668
TI  - Cadmium-induced upregulation of lipid peroxidation and reactive oxygen species
      caused physiological, biochemical, and ultrastructural changes in upland cotton
      seedlings.
AB  - Cadmium (Cd) toxicity was investigated in cotton cultivar (ZMS-49) using
      physiological, ultrastructural, and biochemical parameters. Biomass-based
      tolerance index decreased, and water contents increased at 500 MUM Cd.
      Photosynthetic efficiency determined by chlorophyll fluorescence and
      photosynthetic pigments declined under Cd stress. Cd contents were more in roots
      than shoots. A significant decrease in nutrient levels was found in roots and
      stem. A significant decrease in nutrient levels was found in roots and stems. In
      response to Cd stress, more MDA and ROS contents were produced in leaves than in
      other parts of the seedlings. Total soluble proteins were reduced in all parts
      except in roots at 500 MUM Cd. Oxidative metabolism was higher in leaves than
      aerial parts of the plant. There were insignificant alterations in roots and
      leaves ultrastructures such as a little increase in nucleoli, vacuoles, starch
      granules, and plastoglobuli in Cd-imposed stressful conditions. Scanning
      micrographs at 500 MUM Cd showed a reduced number of stomata as well as near
      absence of closed stomata. Cd depositions were located in cell wall, vacuoles,
      and intracellular spaces using TEM-EDX technology. Upregulation of oxidative
      metabolism, less ultrastructural modification, and Cd deposition in dead parts of
      cells show that ZMS-49 has genetic potential to resist Cd stress, which need to
      be explored.

PMID- 24459669
TI  - F-18 labeled vasoactive intestinal peptide analogue in the PET imaging of colon
      carcinoma in nude mice.
AB  - As large amount of vasoactive intestinal peptide (VIP) receptors are expressed in
      various tumors and VIP-related diseases, radiolabeled VIP provides a potential
      PET imaging agent for VIP receptor. However, structural modification of VIP is
      required before being radiolabeled and used for VIP receptor imaging due to its
      poor in vivo stability. As a VIP analogue, [R(8, 15, 21), L(17)]-VIP exhibited
      improved stability and receptor specificity in preliminary studies. In this
      study, F-18 labeled [R(8,15,21), L(17)]-VIP was produced with the radiochemical
      yield being as high as 33.6% +/- 3% (decay-for-corrected, n = 5) achieved within
      100 min, a specific activity of 255 GBq/ MUmol, and a radiochemical purity as
      high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page
      radioautography. A biodistribution study in normal mice also demonstrated fast
      elimination of F-18 labeled [R(8,15,21), L(17)]-VIP in the blood, liver, and
      gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma
      bearing mice confirmed the high tumor specificity, with the tumor/muscle
      radioactivity uptake ratio being as high as 3.03 at 60 min following injection,
      and no apparent radioactivity concentration in the intestinal tracts. In
      addition, blocking experiment and Western Blot test further confirmed its
      potential in PET imaging of VIP receptor-positive tumor.

PMID- 24459670
TI  - Psoriasis: female skin changes in various hormonal stages throughout life-
      puberty, pregnancy, and menopause.
AB  - Psoriasis is one of the most prevalent immune mediated skin diseases worldwide.
      Despite the large prevalence in both men and women, the pathogenesis of this
      disease has not yet been fully clarified. Nowadays, it is believed that psoriasis
      is most likely a T helper Th1/Th17 induced inflammatory disease. Stressful life
      situations are known to cause flare-ups and psoriasis activity may be linked to
      stress from major life events. We know that stress greatly affects both the
      hormone and immune systems and that there are many different hormonal phases
      throughout a woman's lifetime. The severity of psoriasis may fluctuate or be
      influenced by each phase and this relationship can be seen as disease frequency
      seems to peak during puberty, postpartum, and menopause when hormone levels fall,
      while symptoms improve during pregnancy, a state when hormone levels are
      increased. 

PMID- 24459671
TI  - Intravenous transplantation of mesenchymal stromal cells to enhance peripheral
      nerve regeneration.
AB  - Peripheral nerve injury is a common and devastating complication after trauma and
      can cause irreversible impairment or even complete functional loss of the
      affected limb. While peripheral nerve repair results in some axonal regeneration
      and functional recovery, the clinical outcome is not optimal and research
      continues to optimize functional recovery after nerve repair. Cell
      transplantation approaches are being used experimentally to enhance regeneration.
      Intravenous infusion of mesenchymal stromal cells (MSCs) into spinal cord injury
      and stroke was shown to improve functional outcome. However, the repair potential
      of intravenously transplanted MSCs in peripheral nerve injury has not been
      addressed yet. Here we describe the impact of intravenously infused MSCs on
      functional outcome in a peripheral nerve injury model. Rat sciatic nerves were
      transected followed, by intravenous MSCs transplantation. Footprint analysis was
      carried out and 21 days after transplantation, the nerves were removed for
      histology. Labelled MSCs were found in the sciatic nerve lesion site after
      intravenous injection and regeneration was improved. Intravenously infused MSCs
      after acute peripheral nerve target the lesion site and survive within the nerve
      and the MSC treated group showed greater functional improvement. The results of
      study suggest that nerve repair with cell transplantation could lead to greater
      functional outcome. 

PMID- 24459672
TI  - Site-specific distribution of CD68-positive microglial cells in the brains of
      human midterm fetuses: a topographical relationship with growing axons.
AB  - Using 5 fetuses of gestational age (GA) of 15-16 weeks and 4 of GA of 22-25
      weeks, we examined site- and stage-dependent differences in CD68-positive
      microglial cell distribution in human fetal brains. CD68 positive cells were
      evident in the floor of the fourth ventricle and the pons and olive at 15-16
      weeks, accumulating in and around the hippocampus at 22-25 weeks. At both stages,
      the accumulation of these cells was evident around the optic tract and the
      anterior limb of the internal capsule. When we compared CD68-positive cell
      distribution with the topographical anatomy of GAP43-positive developing axons,
      we found that positive axons were usually unaccompanied by CD68-positive cells,
      except in the transpontine corticofugal tract and the anterior limb of the
      internal capsule. Likewise, microglial cell distribution did not correspond with
      habenulointerpeduncular tract. Therefore, the distribution of CD68-positive cells
      during normal brain development may not reflect a supportive role of these
      microglia in axonogenesis of midterm human fetuses. 

PMID- 24459673
TI  - Role of reactive oxygen species in pathogenesis of radiocontrast-induced
      nephropathy.
AB  - In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of
      reactive oxygen species (ROS) in the kidney following the administration of
      iodinated contrast media, which play a relevant role in the development of
      contrast media-induced nephropathy. Many studies indeed support this possibility,
      suggesting a protective effect of ROS scavenging or reduced ROS formation with
      the administration of N-acetylcysteine and bicarbonate infusion, respectively.
      Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are
      prone to enhanced renal parenchymal hypoxia and ROS formation. In this review,
      the association of renal hypoxia and ROS-mediated injury is outlined. Generated
      during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular
      and vascular endothelial injury and might further intensify renal parenchymal
      hypoxia by virtue of endothelial dysfunction and dysregulation of tubular
      transport. Preventive strategies conceivably should include inhibition of ROS
      generation or ROS scavenging. 

PMID- 24459674
TI  - Effects of diphenyl diselenide on methylmercury toxicity in rats.
AB  - This study investigates the efficacy of diphenyl diselenide [(PhSe)2] in
      attenuating methylmercury- (MeHg-)induced toxicity in rats. Adult rats were
      treated with MeHg [5 mg/kg/day, intragastrically (i.g.)] and/ or (PhSe)2 [1
      mg/kg/day, intraperitoneally (i.p.)] for 21 days. Body weight gain and motor
      deficits were evaluated prior to treatment, on treatment days 11 and 21. In
      addition, hepatic and cerebral mitochondrial function (reactive oxygen species
      (ROS) formation, total and nonprotein thiol levels, membrane potential
      (DeltaPsim), metabolic function, and swelling), hepatic, cerebral, and muscular
      mercury levels, and hepatic, cerebral, and renal thioredoxin reductase (TrxR)
      activity were evaluated. MeHg caused hepatic and cerebral mitochondrial
      dysfunction and inhibited TrxR activity in liver (38,9%), brain (64,3%), and
      kidney (73,8%). Cotreatment with (PhSe)2 protected hepatic and cerebral
      mitochondrial thiols from depletion by MeHg but failed to completely reverse
      MeHg's effect on hepatic and cerebral mitochondrial dysfunction or hepatic,
      cerebral, and renal inhibition of TrxR activity. Additionally, the cotreatment
      with (PhSe)2 increased Hg accumulation in the liver (50,5%) and brain (49,4%) and
      increased the MeHg-induced motor deficits and body-weight loss. In conclusion,
      these results indicate that (PhSe)2 can increase Hg body burden as well as the
      neurotoxic effects induced by MeHg exposure in rats. 

PMID- 24459676
TI  - Compound odontoma involving the four quadrants of the jaws: a case report and
      review of the literature.
AB  - Odontomas are the most common odontogenic tumors, representing 70% of all
      odontogenic tumors. They may present in two specific forms; compound odontoma
      forms multiple small tooth-like structures, while complex odontoma forms an
      amorphous calcified mass. In this report, we present a 27-year-old male patient
      with multiple compound odontoma occupied regions at his jaws. The odontomas
      involve both alveolar and basal processes of the maxilla and mandible as well as
      both maxillary sinuses. Converse to conventional recommended treatment, which is
      surgical excision of the lesion, the management was removal of the lesion and
      clinical-radiologic followup. The first year's follow-up findings are presented
      in this case report. 

PMID- 24459675
TI  - Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show
      equivalent antitumor activity.
AB  - We have generated, via somatic cell nuclear transfer, two independent lines of
      transnuclear (TN) mice, using as nuclear donors CD8 T cells, sorted by tetramer
      staining, that recognize the endogenous melanoma antigen TRP1. These two lines of
      nominally identical specificity differ greatly in their affinity for antigen
      (TRP1(high) or TRP1(low)) as inferred from tetramer dissociation and peptide
      responsiveness. Ex vivo-activated CD8 T cells from either TRP1(high) or TRP1(low)
      mice show cytolytic activity in 3D tissue culture and in vivo, and slow the
      progression of subcutaneous B16 melanoma. Although naive TRP1(low) CD8 T cells do
      not affect tumor growth, upon activation these cells function indistinguishably
      from TRP1(high) cells in vivo, limiting tumor cell growth and increasing mouse
      survival. The anti-tumor effect of both TRP1(high) and TRP1(low) CD8 T cells is
      enhanced in RAG-deficient hosts. However, tumor outgrowth eventually occurs,
      likely due to T cell exhaustion. The TRP1 TN mice are an excellent model for
      examining the functional attributes of T cells conferred by TCR affinity, and
      they may serve as a platform for screening immunomodulatory cancer therapies. 

PMID- 24459677
TI  - Quantic molecular resonance scalpel vs traditional scalpel in the treatment of
      labial mucocele: a two-center randomized controlled trial.
AB  - OBJECTIVE: The aim of this randomized two-center study was to compare quantic
      molecular resonance scalpel (QMRS) with traditional scalpel (TS) for the surgical
      treatment of labial mucoceles, in terms of impact on quality of life and
      postoperative pain (primary outcomes) and postsurgical lip paresthesia and
      recurrence of the lesion (secondary outcomes). METHOD AND MATERIALS: Eighty-five
      consecutive patients with labial mucoceles were randomized to receive traditional
      (46) or QMRS surgery (39) in two Italian University Hospital Centers. Patients
      were asked to complete three different forms during the first week after surgery
      to evaluate quality of life and postoperative pain. Periodic follow-up
      examinations were conducted at 1 week, 1 month, and 3 months after surgery, in
      order to detect recurrence of lesion and/or lip paresthesia. RESULTS: Regarding
      the symptoms reported during the first week after surgery, questionnaires given
      to the patients and the mean painkiller consumption did not demonstrate any
      statistically significant differences within the two groups. Women treated with
      QMRS reported a worse experience than women treated with TS (P < .05). Among all
      the mucoceles treated, during the follow-up period of 3 months, one that had been
      eliminated with the cold scalpel was seen to relapse, versus none of those
      treated with the QMRS (P = 1.0). We reported a localized and terminal paresthesia
      of the labial mucosa close to the surgical site in 10.58% of the total patients.
      Comparing the QMRS with TS, we observed a greater incidence of neurologic
      complications with the latter technique (P = .035). CONCLUSION: This is the first
      prospective randomized study to report outcome data and 3-month follow-up of a
      cohort of patients suffering from labial mucoceles. QMRS for surgical removal of
      labial mucoceles seems to be comparable to traditional scalpel in terms of
      postoperative quality of life, pain, and postsurgical lip paresthesia.

PMID- 24459678
TI  - Evaluation of postoperative discomfort after impacted mandibular third molar
      surgery using three different types of flap.
AB  - OBJECTIVE: The surgical extraction of an impacted third molar involves a wide
      range of consequences such as trismus, swelling, and pain, as well as more
      significant complications, temporary or permanent, that can manifest altered
      sensitivity of the tongue or lips. The purpose of this prospective study was to
      evaluate the effects of three different flaps on postoperative discomfort
      considering trismus, edema, and pain, after the extraction of impacted third
      molars. The data derived from the analysis of the surgical trials performed at
      the Oral Surgery Unit, Department of Surgical, Reconstructive and Diagnostic
      Sciences, IRCCS Policlinico, University of Milan, directed by Professor F.
      Santoro, MD. METHOD AND MATERIALS: This study, developed over 2 years, involved
      238 patients for a total of 238 extractions of impacted mandibular third molars.
      The 238 surgeries were performed on 114 men and 124 women: 54 avulsions were
      performed with the elevation of an envelope flap (Group 1), 48 avulsions through
      the elevation of a triangular flap (Group 2), and the remaining 136 avulsions
      were performed using a trapezoidal flap (Group 3). RESULTS: Trismus was
      significantly reduced (P < .05) in patients treated with envelope flap, as was
      the swelling perceived by the patient (P < .05). Pain was closely related to the
      elevation of a mucoperiosteal flap and osteotomy. Our study does not reveal
      statistically significant differences between the three types of flap used;
      however, the number of analgesic tablets taken was lower in cases of elevation of
      a less traumatic flap (envelope and triangular flaps). CONCLUSION: The data
      collected in this study indicate the envelope flap as the most suitable for the
      reduction of the expression of postoperative complications such as swelling and
      trismus.

PMID- 24459679
TI  - Restoration of a partially edentulous patient with an implant-supported removable
      partial denture: a case report.
AB  - The aim of this report is to present and discuss the clinical procedure of an
      implant-supported removable partial denture for a partially edentulous patient
      who exhibited a severely resorbed ridge and a collapsed vertical stop. The 67
      year-old partially edentulous patient presented with a lack of vertical stop and
      an advanced transverse arch discrepancy. For the maxilla, an implant-supported
      removable partial denture was fabricated on bilateral distal implant abutments.
      The mandibular arch was restored with an implant-supported fixed partial denture,
      since it was expected to function more properly than a removable partial denture.
      This clinical report demonstrates a successful treatment approach to restore oral
      function and appearance for the patient. 

PMID- 24459680
TI  - Unsplinted implants retaining a mandibular overdenture with magnetic attachments:
      a short-term clinical study in controlled type 2 diabetic patients.
AB  - OBJECTIVE: This short-term prospective study evaluated the clinical outcome of
      unsplinted implants retaining a mandibular overdenture with magnetic attachments
      in controlled type 2 diabetic patients. METHOD AND MATERIALS: Twenty-eight
      completely edentulous patients (18 men and 10 women) with controlled type 2
      diabetes mellitus received a total of 56 implants (two per patient) in the canine
      region of the mandible using the standardized two-stage surgical protocol. All
      patients complained of insufficient retention of their mandibular denture. New
      maxillary complete dentures and mandibular overdentures were fabricated.
      Overdentures were connected to the implants with magnetic attachments. Each
      implant was evaluated at the time of prosthetic loading, and 6, 12, and 24 months
      thereafter. Clinical evaluation was performed using Gingival Index (GI), Plaque
      Index (PI), probing depth (PD), implant stability (ISQ), and vertical bone loss
      (VBLO). Cumulative success and survival rates were calculated using life table
      analysis. RESULTS: After 2 years of overdenture insertion, there was a
      significant increase in PI, GI, PD, and VBLO. ISQ decreased significantly after 6
      months of loading then increased again after 2 years. The cumulative survival and
      success rates of the implants were 91% and 87.5% respectively. CONCLUSION: Within
      the limitations of this study, the clinical outcome of unsplinted implants
      retaining a mandibular overdenture with magnetic attachments in controlled type 2
      diabetic patients was favorable after 2 years. However, long-term randomized
      controlled trials are needed to compare the clinical outcome of unsplinted
      implants in diabetic and nondiabetic patients.

PMID- 24459681
TI  - On the edge between medicine and dentistry: review of the dentist's role in the
      diagnosis and treatment of snoring and sleep apnea.
AB  - OBJECTIVES: Snoring and obstructive sleep apnea syndrome (OSA) can affect both
      esthetics and health. In this review article, we describe the role of the dentist
      in evaluation and treatment of snoring and OSA in children and adults, with an
      emphasis on oral appliances as a means to treat the adult population. DATA
      SOURCES: A comprehensive literature search of publications from 1934 to 2013 in
      the PubMed/Medline/Science Direct databases was performed to collect information
      about snoring, OSA, and oral or dental appliances using these terms as key words.
      The search was limited to peer-reviewed articles written in English, with a few
      exceptions in other languages. The literature search was endorsed by manual
      searching through peer-reviewed journals and reference lists of the selected
      articles. CONCLUSION: The dentist's role in the diagnosis of OSA in children and
      in diagnosis and treatment in the adult population with the help of oral
      appliances is vital. Diagnosis and treatment by the aware dentist can reduce
      major health risk outcomes.

PMID- 24459682
TI  - An ortho-surgical approach to severe impaction using bone crestal bridge: a case
      report.
AB  - Impaction of both mandibular canine and lateral incisor is a rare clinical
      finding which is often treated by way of surgical extraction. This decision is
      often taken because of the anatomical limitations presented by the mandible, and
      the horizontal position of the impacted teeth, which have occasionally
      transmigrated, placing them in close proximity to the roots of neighboring teeth
      and with a high risk for causing their resorption. In addition, this condition
      significantly increases the likelihood that the area involved will undergo
      gingival recession and loss of crestal bone if an unsophisticated ortho-surgical
      approach is undertaken. The present report describes a novel ortho-surgical
      technique which maintains the alveolar crestal bone and utilizes a lingual arch
      attached to the first molars with traction through tunneling with super-elastic
      springs. This combined approach eliminated the need for extraction of the
      impacted teeth, and accomplished their full alignment without any of the
      aforementioned side effects. Every dentist (general practitioners as well as
      specialists) should be aware of this procedure and refer patients to a
      specialist. 

PMID- 24459683
TI  - Povidone-iodine gel and solution as adjunct to ultrasonic debridement in
      nonsurgical periodontitis treatment: an RCT pilot study.
AB  - OBJECTIVES: Polyvinylpyrrolidone-iodine (PVP-iodine or povidone- iodine) enhances
      the treatment outcomes of initial periodontal treatment but the degree of benefit
      varies in the literature. A main reason might be the concentration of the dosage
      form and its contact time with the periodontal tissues. In this randomized pilot
      study the effect of repeated subgingival application of PVP-iodine during scaling
      and root planing (SRP) was assessed. Changes of clinical parameters and
      microbiotic taxa after 3 months were analyzed. METHOD AND MATERIALS: In a split
      mouth design 12 patients with generalized, severe periodontitis were treated with
      SRP combined with subgingival application of either PVP-iodine or water. Test and
      control sides were isolated with a special rubber dam technique. Irrigations were
      reapplied during SRP. Periodontal probing depth (PD) and recessions were
      documented before treatment and after 3 months. Samples of subgingival bacteria
      before SRP and after 1 week, 1 month, and 3 months were analyzed. RESULTS: Three
      months after SRP, changes for PD and recession in deep pockets were significantly
      higher in the PVP-iodine group (P = .012 and .044 respectively). The number of
      these pockets was reduced from 73 at baseline to 8 in the test and 19 in the
      control group. In both groups, bacterial taxa were reduced after 1 week. One
      month after SRP only taxa of Porphyromonas gingivalis in the PVP-iodine group
      were lower than at baseline. After 3 months, all taxa regained baseline values.
      CONCLUSION: PVP-iodine reapplied frequently during SRP might enhance pocket depth
      reduction in initially deep pockets.

PMID- 24459684
TI  - A novel fluorescent chemosensor allows the assessment of intracellular total
      magnesium in small samples.
AB  - The present study investigated the analytical capabilities of a new fluorescent
      chemosensor, named DCHQ5, a phenyl derivative belonging to the family of diaza
      crown-hydroxyquinolines, for the quantitative assessment of total intracellular
      Mg content. The results obtained were compared to the analytical performances of
      DCHQ1 - the parent probe of the series which so far was the only suitable species
      for the quantitative assessment of the intracellular total magnesium and showed
      comparable results to atomic absorption spectroscopy. Different protocols were
      tested in several cell lines both by flow cytometry and by steady state
      fluorescence spectroscopy assays. The results obtained support the possibility to
      use DCHQ5 to accurately quantify the intracellular total Mg in much smaller
      samples than DCHQ1, also displaying an increased stable intracellular staining.
      These features, combined with the high fluorescence enhancement upon cation
      binding, and the possibility to be excited both in the UV and visible region,
      make DCHQ5 a valuable and versatile analytical tool for Mg assessment in
      biological samples. 

PMID- 24459685
TI  - Assessing cerebrospinal fluid abnormalities in neurosyphilis patients  without
      human immunodeficiency virus infection.
AB  - Neurosyphilis (NS) caused by Treponema pallidum (T. pallidum) subspecies
      pallidum, can affect the central nervous system during any stage of the disease.
      To assess several laboratory parameters for NS diagnosis, we performed a case
      control study on 42 hospitalized NS patients negative for human immunodeficiency
      virus (HIV) and 40 syphilis/non-NS patients, excluding NS patients at Xiamen
      Zhongshan Hospital from June 2010 to June 2011. Multivariate logistic regression
      model showed that the cerebrospinal fluid white blood cell (CSF-WBC, P = 0.009)
      levels, the CSF-LDH (P = 0.006) levels, the albumin quotient (P = 0.009) and the
      IgA index (P = 0.042) were independently associated with high risk of NS. The
      receiver operator characteristic (ROC) curve analysis revealed that the optimal
      cut-offs were 10 * 106 cells/L for the CSF-WBC concentration, 19.3 U/L for the
      CSF lactate dehydrogenase (LDH) concentration, 7.08 for the albumin quotient, and
      0.14 for the IgA index. Combining the CSF-WBC level, the CSF-LDH level, the
      albumin quotient and the IgA index increased the NS diagnosis sensitivity to
      97.6%. T. pallidum particle agglutination (TPPA) index significantly correlated
      with the CSF-WBC (r = 0.453, P = 0.000), the IgA index (r = 0.446, P = 0.000),
      the albumin quotient (r = 0.262, P = 0.017), and the CSF-LDH (r = - 0.278, P =
      0.012), respectively. In addition, there were correlations between the CSF-WBC
      and the IgA index (r = 0.329, P = 0.003), and between the CSF-WBC and the albumin
      quotient (r = 0.306, P = 0.005). Our results indicated that simultaneous testing
      of CSF-WBC levels, albumin quotient, IgA index and CSF-LDH can help predict the
      likelihood of NS in HIV-negative patients.

PMID- 24459686
TI  - An approach to the problem of violence against healthcare workers: the right to
      safe and healthy working conditions and to dignity at work.

PMID- 24459687
TI  - Brown adipose tissue as a therapeutic target for human obesity.
AB  - Brown adipose tissue (BAT) is the major site of sympathetically activated
      adaptive thermogenesis during cold exposure and after spontaneous hyperphagia,
      thereby controlling whole-body energy expenditure and body fat. Recent
      radionuclide studies have demonstrated the existence of metabolically active BAT
      in healthy adult humans. Human BAT is activated by acute cold exposure, being
      positively correlated to cold-induced increases in energy expenditure. The
      metabolic activity of BAT is lower in older and obese individuals. The inverse
      relationship between the BAT activity and body fatness suggests that BAT, because
      of its energy dissipating activity, is protective against body fat accumulation.
      In fact, either repeated cold exposure or daily ingestion of some food
      ingredients acting on transient receptor potential channels recruited BAT in
      association with increased energy expenditure and decreased body fat even in
      individuals with low BAT activities before the treatment. Thus, BAT is a
      promising therapeutic target for combating human obesity and related metabolic
      disorders.

PMID- 24459688
TI  - Regulation of hepatic branched-chain alpha-ketoacid dehydrogenase complex in rats
      fed a high-fat diet.
AB  - Branched-chain alpha-ketoacid (BCKA) dehydrogenase complex (BCKDC) regulates
      branched-chain amino acid (BCAA) metabolism at the level of BCKA catabolism. It
      has been demonstrated that the activity of hepatic BCKDC is markedly decreased in
      type 2 diabetic animal models. In this study, we examined the regulation of
      hepatic BCKDC in rats with diet-induced obesity (DIO). Rats were fed a control or
      a 60% of energy high-fat diet (HFD) for twelve weeks. Concentrations of blood
      components and the activities and protein amounts of hepatic BCKDC and its
      specific kinase (BDK) were measured. The concentrations of plasma glucose,
      insulin, and corticosterone were significantly elevated in DIO rats compared to
      those fed the control diet, suggestive of insulin resistance. Blood BCAA
      concentrations were not increased. The activity of hepatic BCKDC that was present
      in the active form in the liver was higher in DIO rats compared to controls,
      although the total activity and the enzyme amount were not different between two
      diet groups. The activity of hepatic BDK and the abundance of BDK bound to the
      BCKDC were decreased in DIO rats. The total amount of hepatic BDK was also
      significantly decreased in DIO rats. In rats made obese through HFD feeding, in
      contrast to prior studies in rat models of type 2 diabetes, hepatic BDK was down
      regulated and thereby hepatic BCKDC was activated, suggesting that DIO promotes
      liver BCKA catabolism. In this model there was no evidence that increased blood
      BCAAs drive DIO-associated insulin resistance, since concentrations of BCAAs were
      not altered by DIO.

PMID- 24459690
TI  - Understanding the causes of suicide: psychological autopsies should not be our
      only resource.

PMID- 24459691
TI  - Psychotic symptoms induced by clarithromycin and chlorpheniramine.

PMID- 24459689
TI  - Improvement in erectile function following weight loss in obese men: the SHED-IT
      randomized controlled trial.
AB  - In a randomized controlled trial 145 sexually active overweight/obese men
      received either a male only SHED-IT (Self Help Exercise and Diet Using IT) weight
      loss program or a wait-list control. Erectile function (IIEF-5) was compared
      between men in the active intervention versus controls. IIEF-5 was assessed at
      baseline, 3 months (post-intervention) and 6 months (3-month follow-up).
      Intention-to-treat analysis revealed a significant intervention effect for
      erectile function (p = 0.018) at 6 months (+1.4; 95% CI 0.3,2.4; d = 0.32). A
      minimal contact, gender-tailored weight loss program significantly improved men's
      erectile function. Further studies evaluating change in erectile function with
      weight loss are warranted.

PMID- 24459692
TI  - A multifunctional bilayered microstent as glaucoma drainage device.
AB  - Commercial non-degradable glaucoma implants are often associated with undesired
      hypotony, fibrosis, long term failure, and damage of adjacent tissues, which may
      be overcome by a multifunctional polymeric microstent for suprachoroidal
      drainage. This study reports the design and fabrication of such devices with
      tailorable internal diameters (50-300 MUm) by solvent-free, continuous hot melt
      extrusion from blends of poly[(epsilon-caprolactone)-co-glycolide] and
      poly(epsilon-caprolactone) [PCL]. A spatially directed release was supported by
      bilayered microstents with an internal drug-free PCL layer, and a quantitative
      description of release kinetics with diclofenac sodium as model drug was
      provided. Furthermore, the slow degradation pattern (> 1 year) was analyzed and
      potential effects of 1-5 wt.% drug loading on material properties were excluded.
      Translational aspects including sterilization by gamma-irradiation on dry ice, in
      vitro biocompatibility, and in vivo implantation were addressed. The promising
      results support further functional analysis of long-term in vivo performance and
      suppression of disadvantageous capsule formation.

PMID- 24459693
TI  - Liposome co-encapsulation of synergistic combination of irinotecan and
      doxorubicin for the treatment of intraperitoneally grown ovarian tumor xenograft.
AB  - Liposome co-encapsulation of synergistic anti-cancer drug combination is an
      emerging area that has demonstrated therapeutic benefit in clinical trials.
      Remote loading of two or more drugs into a single liposome constitutes a new
      challenge that calls for a re-examination of drug loading strategies to allow the
      loading of the drug combination efficiently and with high drug content. In this
      study, the Mn(2+) gradient coupled with A23187 ionophore was applied in the
      sequential co-encapsulation of doxorubicin and irinotecan, as this drug loading
      method is capable of remotely loading drugs by apparently two different
      mechanisms, namely, coordination complexation and pH gradient. Doxorubicin and
      irinotecan could be co-encapsulated into liposomes in a wide range of drug-to
      drug ratios, with encapsulation efficiencies of > 80%. The total encapsulated
      drug content was non-linearly correlated with increases in the intraliposomal
      Mn(2+) concentration, with a maximum total drug-to-lipid molar ratio of 0.8:1
      achieved with 600 mM Mn(2+). This high encapsulated drug content did not affect
      the stability of the co-encapsulated liposomes upon storage for six months.
      Regardless of the encapsulated drug amount, the liposomes did not exhibit the
      fiber bundle precipitate morphology but rather an undefined structural
      organization in the aqueous core. The co-encapsulated liposome formulation was
      further tested in an intraperitoneally grown, human ovarian tumor xenograft
      model, and was shown to significantly improve the survival of the tumor-bearing
      animals. The improvement in therapeutic efficacy was possibly due to the increase
      in systemic drug exposure, with the maintenance of the synergistic molar drug
      ratio of 1:1 in circulation.

PMID- 24459694
TI  - Author's response.

PMID- 24459695
TI  - ANSO study: evaluation in an indoor environment of a mobile assistance robotic
      grasping arm.
AB  - OBJECTIVE: To evaluate the reliability and functional acceptability of the
      ''Synthetic Autonomous Majordomo'' (SAM) robotic aid system (a mobile Neobotix
      base equipped with a semi-automatic vision interface and a Manus robotic arm).
      MATERIALS AND METHODS: An open, multicentre, controlled study. We included 29
      tetraplegic patients (23 patients with spinal cord injuries, 3 with locked-in
      syndrome and 4 with other disorders; mean SD age: 37.83 13.3) and 34 control
      participants (mean SD age: 32.44 11.2). The reliability of the user interface was
      evaluated in three multi-step scenarios: selection of the room in which the
      object to be retrieved was located (in the presence or absence of visual control
      by the user), selection of the object to be retrieved, the grasping of the object
      itself and the robot's return to the user with the object. A questionnaire was
      used to assess the robot's user acceptability. RESULTS: The SAM system was stable
      and reliable: both patients and control participants experienced few failures
      when completing the various stages of the scenarios. The graphic interface was
      effective for selecting and grasping the object - even in the absence of visual
      control. Users and carers were generally satisfied with SAM, although only a
      quarter of patients said that they would consider using the robot in their
      activities of daily living.

PMID- 24459696
TI  - Center of pressure path during Sit-to-walk tasks in young and elderly humans.
AB  - OBJECTIVE: This study aimed to investigate differences in total center of
      pressure (TCOP) paths during a Sit-to-Walk task in young and elderly subjects.
      METHOD: Nine young and 19 elderly subjects were asked to repeat five Sit-to-Walk
      tasks. The COP paths were computed during the rising from vertical forces.
      RESULTS: For 4 young and 17 elderly subjects, the TCOP moved on the anterior
      posterior axis during the 1st period (from the beginning of the rising to maximal
      force under the swing leg) and then joined the stance foot during the 2nd period
      (from maximal force to the toe off). For the two other paths observed in young
      subjects, the duration of the 2nd period was increased (33% of total duration vs.
      18%, P = 0.02) or the area of TCOP displacement during the 1st period was
      decreased. CONCLUSION: During the Sit-to-Walk task, different TCOP paths can be
      described in relation to age. These profiles are influenced by the level of
      postural stability required before initiating the first step. After further
      validation, the analysis of TCOP paths could be used to estimate the level of
      postural ability, especially in the elderly.

PMID- 24459697
TI  - Effects of heavy drinking on executive cognitive functioning in a community
      sample.
AB  - BACKGROUND: Deficits in several aspects of executive cognitive functioning (ECF)
      have been consistently associated with alcohol use disorders. Most of this
      research, however, has been conducted in alcohol dependent patient samples. A
      handful of recent studies, primarily in college students, have also reported
      similar deficits, but little is known about the effects of heavy drinking in
      adult, non-patient men and women. METHODS: A community sample (N = 560) of men
      and women completed a brief battery of ECF measures including measures of
      attentional control, cognitive flexibility, working memory and response
      inhibition.Quantity/frequency of alcohol and illicit drug use in the past year
      were also assessed. RESULTS: Regression analyses indicated that men and women
      with higher levels of alcohol consumption exhibited greater impairment on several
      ECF measures, primarily those pertaining to cognitive flexibility and response
      inhibition. These results remained after controlling for demographic factors such
      as age, gender, education, and illicit drug use. CONCLUSIONS: These findings
      support and extend prior work documenting the deleterious effects of heavy
      alcohol consumption on ECF in a community sample and specifically indicate robust
      effects on cognitive flexibility,psychomotor speed, and response inhibition.

PMID- 24459698
TI  - A life history perspective on skin cancer and the evolution of skin pigmentation.
AB  - The ancestral state of human skin pigmentation evolved in response to high
      ultraviolet radiation (UVR) stress. Some argue that pigmentation evolved to limit
      folate photolysis, therein limiting neural tube defects. Pigmentation also
      protects against sunburn which decreases the efficiency of sweating and
      potentiates skin infection. Pigmentation increases the efficacy of skin as a
      barrier to infection. Skin cancer has been rejected or minimized as a selective
      pressure because it is believed to have little or no effect on mortality during
      reproductive years. This argument ignores evidence of human longevity as a
      derived life history trait and the adaptive value of investment in offspring and
      kin, particularly during the post-reproductive lifespan. Opponents argue that
      lifespan in prehistoric hunter-gatherers was too short to be relevant to the
      evolution of skin pigmentation. This argument is flawed in that it relies on
      estimates of longevity at birth rather than adolescence. When appropriate
      estimates are used, it is clear that human longevity has a deep evolutionary
      history. We use a life history perspective to demonstrate the value of skin
      pigmentation as an adaptation to skin cancer with the following points: UVR
      exposure increases dysregulation of gene expression in skin cells leading to
      immortal cell lines; cutaneous malignant melanoma (CMM) affects individuals
      throughout reproductive years; and lifespan was longer than has previously been
      acknowledged, providing the opportunity for kin selection. This hypothesis is not
      at odds with the folate or barrier hypotheses. We stress that the evolution of
      skin pigmentation is complex and is an ongoing process.

PMID- 24459699
TI  - Response.

PMID- 24459700
TI  - Circulating microRNA profiles altered in mice after 28 d exposure to
      perfluorooctanoic acid.
AB  - Perfluorooctanoic acid (PFOA) is a stable man-made compound with many industrial
      and commercial uses. Recently, however, concern has been raised that it may
      induce various toxicological effects such as hepatotoxicity, immunotoxicity, and
      developmental toxicity. Because levels of circulating microRNAs (miRNAs) can be
      altered in several clinical diseases, they may serve as potential novel
      biomarkers. Here,we explored differences in the profiles of circulating miRNAs in
      mice after PFOA exposure. Using TaqMan miRNA arrays, we determined that the
      levels of 24 circulating miRNAs were altered in mice dosed with PFOA at 1.25
      mg/kg/d and 73 were altered in mice dosed with 5 mg/kg/d. Eight miRNAs were
      further validated using TaqMan Real-Time PCR assays. Results were consistent with
      those obtained from the TaqMan miRNA arrays, except for miR-199a-3p. The most
      remarkable of the circulating miRNAs (miR-26b-5p and miR-199a-3p) were also up
      regulated in the serum of occupational workers in our previous epidemiological
      study. We also found similar patterns in mice exposed to PFOS. These results
      demon-strated that circulating miRNA profiles were altered after exposure to high
      concentrations of PFOA and miR-28-5p, miR-32-5p, miR-122-5p, miR-192-5p, and miR
      26b-5p in serum may be linked to effects of PFOA, especially in occupationally
      exposed people.

PMID- 24459701
TI  - Dopamine-dependent behavior in adult rats after perinatal exposure to purity
      controlled polychlorinated biphenyl congeners (PCB52 and PCB180).
AB  - Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary,
      regulatory panels have concluded that risk assessment of these congeners is
      hampered or impossible. As the dopaminergic system is one of the main targets in
      PCB-related neurotoxic effects after developmental exposure, we selected
      catalepsy induced by the dopamine receptor blocker haloperidol to characterize
      effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat
      dams. Rat dams were treated with PCB congeners by gavage using six dose levels
      (total doses: PCB52 - 0, 30, 100, 300, 1000 or 3000 mg/kg body wt.; PCB180 - 0,
      10, 30, 100, 300, or 1000 mg/kg body wt.) to allow benchmark dose analysis of the
      results. Testing of adult offspring (starting at 180 days of age) for catalepsy
      induced by injection with haloperidol revealed slightly prolonged latencies to
      movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted
      in more pronounced effects, with generally reduced latencies in male offspring.
      These results indicate reduced dopaminergic activity after PCB52 exposure,
      whereas the outcome for PCB180 may be related to increased extracellular dopamine
      as reported in the literature.Benchmark dose analyses revealed that both PCB
      congeners exerted effects mainly at moderate exposure levels. Together, these
      results underline the importance of effects on the dopaminergic system as
      indicated by studies in human females after occupational PCB exposure.

PMID- 24459702
TI  - Alternative biomarkers of n-hexane exposure: characterization of aminoderived
      pyrroles and thiol-pyrrole conjugates in urine of rats exposed to 2,5
      hexanedione.
AB  - The identification of pyrrole derivatives in urine of rats exposed to 2,5
      hexanedione (2,5-HD), was performed to select an adequate peripheral biomarker
      predictive of 2,5-HD neurotoxicity. Studies on molecular mechanism of 2,5-HD
      neurotoxicity have revealed that 2,5-hexanedione reacts with free amino groups of
      lysine in proteins forming primary pyrrole adducts, which may autoxidize and form
      pyrrole dimers, responsible for protein crosslinking in neurofilaments, or react
      with sulfhydryl groups of cysteine in peptides and proteins, forming secondary
      pyrrole adducts, which probably may inhibit the process responsible by 2,5-HD
      neurotoxicity. In this work, the analysis of excreted 2,5-HD and pyr-role
      derivatives in urine of rats i.p. treated with 3 doses of 2,5-HD (400 mg/kg bw/48
      h) was performed using ESI-LC-MS/MS. Several pyrrole compounds were identified,
      namely dimethylpyrrole norleucine(DMPN), cysteine-pyrrole conjugate (DMPN NAC),
      glutathione-pyrrole conjugate (DMPN GSH) and 2,5-dimethylpyrrole (2,5-DMP).
      Additionally, free and total 2,5-HD, DMPN and DMPN NAC were quantified. The
      observed results suggest that DMPN is a sensitive and specific indicator of
      repeated exposure to 2,5-HD.

PMID- 24459703
TI  - HDAC inhibitors reverse acquired radio resistance of KYSE-150R esophageal
      carcinoma cells by modulating Bmi-1 expression.
AB  - Tumors treated with fractionated doses of ionizing radiation (IR) often acquire
      radioresistance. Although histone deacetylase inhibitors (HDIs) have been
      demonstrated to sensitize intrinsic radioresistant cancer cell lines to IR,
      little is known on the impact of HDIs on the effects of IR in acquired
      radioresistant cancer cells. This study evaluates the mechanisms by which HDIs
      sensitize acquired radioresistant esophageal squamous cell carcinoma cells to IR.
      The HDIs trichostatin A and sodium butyrate were tested for the irability to
      sensitize acquired radioresistant KYSE-150R and radiosensitive KYSE-150 parental
      cells to IR. Although the HDIs induced similar levels of cytotoxicity in the KYSE
      150 and the KYSE-150R cells, HDIs increased the: (i) radiosensitivity, (ii) IR
      induced ROS generation, and (iii) IR-induced G2/M arrest and apoptosis of KYSE
      150R cells compared with those of KYSE-150 cells. These changes were accompanied
      by increased p21 expression and decreased mitochondrial membrane potential. When
      combined with IR, HDIs inhibited Bmi-1 expression in KYSE-150R cells and their
      ability to repair DNA damage. The results demonstrate the potential utility of
      HDIs in augmenting the efficacy of fractionated radiotherapy.

PMID- 24459704
TI  - Base excision DNA repair defect in thioredoxin-1 (Trx1)-deficient cells.
AB  - Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the
      removal of oxidative stress. We investigated the mechanism by which the redox
      modulator Trx1 affects base excision repair (BER) activity to understand the
      protective role of Trx1. We constructed a Trx1 knockdown system to demonstrate
      the specific mechanism of Trx1 shRNA cells compared with that in the wild type
      cells, leading to increased cellular susceptibility to a sublethal dose of BER
      inducible toxicant, nitrosomethylurea (NMU). In addition, we observed a
      modulatory role of Trx1 in the BER pathway via the p53 downstream gene, growth
      arrest, and DNA-damage-inducible protein 45 alpha (Gadd45a). The protein level
      and function of p53, a Trx1 downstream gene, coincidently decreased in the Trx1
      shRNA cells. Futhermore, Trx1 shRNA cells showed decreased Gadd45a expression and
      interaction of Gadd45a with apurinic/apyrimidinic endonuclease 1 (APE1) as well
      as APE activity. In conclusion, Trx1 might cooperate in the control of APE1
      function by modulating the p53-mediated BER via the protein-protein interaction
      between Gadd45a and APE1, providing insight into the novel role of redox factor
      Trx1 in modulation of BER.

PMID- 24459705
TI  - Reproductive outcomes after progestin therapy in infertile women with endometrial
      atypical hyperplasia.

PMID- 24459706
TI  - Comment on the article by Altunyurt, et al. [Eur J Obstet Gynecol Reprod Biol
      2003;107:81-4].

PMID- 24459707
TI  - Reply to the Comment by Professor Jonathan D.C. Ross.

PMID- 24459708
TI  - Comment on: ''Campagne DM, Fact: antidepressants and anxiolytics are not safe
      during pregnancy.'' Eur J Obstet Gynecol Reprod Biol 2007 Dec;135(2):145-8.

PMID- 24459709
TI  - Author's response: Antidepressants and anxiolytics in pregnancy: the facts stand.

PMID- 24459710
TI  - Charities: Profiting from non-profits.

PMID- 24459711
TI  - Turning point: Kristin Laidre. Interviewed by Virginia Gewin.

PMID- 24459712
TI  - From the fundamentals of multiple sclerosis to clinical management.

PMID- 24459713
TI  - Education: Embed social awareness in science curricula.

PMID- 24459714
TI  - Protect the deep sea.

PMID- 24459715
TI  - How to investigate neuro-biochemical relationships on a regional level in humans?
      Methodological considerations for combining functional with biochemical imaging.
AB  - There is an increasing interest in combining different imaging modalities to
      investigate the relationship between neural and biochemical activity. More
      specifically, imaging techniques like MRS and PET that allow for biochemical
      measurement are combined with techniques like fMRI and EEG that measure neural
      activity in different states. Such combination of neural and biochemical measures
      raises not only technical issues, such as merging the different data sets, but
      also several methodological issues. These methodological issues - ranging from
      hypothesis generation and hypothesis-guided use of technical facilities to target
      measures and experimental measures - are the focus of this paper. We discuss the
      various methodological problems and issues raised by the combination of different
      imaging methodologies in order to investigate neuro-biochemical relationships on
      a regional level in humans. For example, the choice of transmitter and scan type
      is discussed, along with approaches to allow the establishment of particular
      specificities (such as regional or biochemical) to in turn make results fully
      interpretable. An algorithm that can be used as a form of checklist for designing
      such multimodal studies is presented. The paper concludes that while several
      methodological and technical caveats needs to be overcome and addressed,
      multimodal imaging of the neuro-biochemical relationship provides an important
      tool to better understand the physiological mechanisms of the human brain.

PMID- 24459716
TI  - Don't rush to rehabilitate Hwang.

PMID- 24459717
TI  - Semi-automatic sleep EEG scoring based on the hypnospectrogram.
AB  - BACKGROUND: Sleep EEG organization is revealed by sleep scoring, a time-consuming
      process based on strictly defined visual criteria. NEW METHOD: We explore the
      possibility of sleep scoring using the whole-night time-frequency analysis,
      termed hypnospectrogram, with a computer-assisted K-means clustering method.
      RESULTS: Hypnograms were derived from 10 whole-night sleep EEG recordings using
      either standard visual scoring under the Rechtshaffen and Kales criteria or semi
      automated analysis of the hypnospectrogram derived from a single EEG electrode.
      We measured substantial agreement between the two approaches with Cohen's kappa
      considering all 7 stages at 0.61. COMPARISON WITH EXISTING METHODS: A number of
      existing automated procedures have reached the level of human inter-rater
      agreement using the standard criteria. However, our approach offers the scorer
      the opportunity to exploit the information-rich graphic representation of the
      whole night sleep upon which the automated method works. CONCLUSION: This work
      suggests that the hypnospectrogram can be used as an objective graphical rep
      resentation of sleep architecture upon which sleep scoring can be performed with
      computer-assisted methods.

PMID- 24459718
TI  - A return to order.

PMID- 24459719
TI  - A question of time.

PMID- 24459720
TI  - Setting a gold standard for quantification of leukoaraiosis burden in patients
      with ischemic stroke: the Atherosclerosis Risk in Communities Study.
AB  - BACKGROUND: Accurate and reliable measurement of leukoaraiosis, or MR-detected
      white, matter hyper-intensity (WMH) burden in subjects with acute ischemic stroke
      (AIS) is important for, ongoing research studies and future models of risk and
      outcome prediction, but the presence of a, cerebral infarct may complicate
      measurement. We sought to assess accuracy of a volumetric method, designed to
      measure WMH in AIS subjects as compared to the previously validated protocol. NEW
      METHOD: We randomly selected and equally sampled 120 brain scans from the
      Atherosclerosis, Risk in Communities (ARIC) MRI Study individuals within
      designated mild, moderate, and severe, tertiles of WMH volume (WMHV). T2 FLAIR
      axial images were analyzed using the AIS WMH volumetric, protocol and compared
      with the ARIC (gold standard) method. Pearson correlation coefficients, linear,
      concordance correlation coefficient, and Blant-Altman procedures were used to
      assess measurement, agreements between the two procedures. RESULTS: Median WMHV
      determined by using the ARIC method was 7.8 cm3 (IQR 5.7-13.55) vs. 3.54 cm3,
      (IQR 2.1-7.2) using the AIS WMH method. There was good correlation between the
      two measurements, (r = 0.52, 0.67, and 0.9 for tertiles 1, 2, and 3 respectively)
      (p < 0.001). COMPARISON WITH EXISTING METHOD: The AIS WMH protocol was specific
      for leukoaraiosis in ischemic, stroke, but it appeared to underestimate WMHV
      compared to the gold standard method. CONCLUSIONS: Estimates of MR-detectable WMH
      burden using a volumetric protocol designed for, analysis of clinical scans
      correlate strongly with gold standard measurements. These findings will,
      facilitate future studies of WMH in normal aging and in patients with stroke and
      other cerebrovascular, disease.

PMID- 24459721
TI  - Histone chaperones and chromatin assembly.

PMID- 24459722
TI  - Assembling chromatin: the long and winding road.
AB  - It has been over 35 years since the acceptance of the "chromatin subunit"
      hypothesis, and the recognition that nucleosomes are the fundamental repeating
      units of chromatin fibers. Major subjects of inquiry in the intervening years
      have included the steps involved in chromatin assembly, and the chaperones that
      escort histones to DNA. The following commentary offers an historical perspective
      on inquiries into the processes by which nucleosomes are assembled on replicating
      and nonreplicating chromatin. This article is part of a Special Issue entitled:
      Histone chaperones and Chromatin assembly.

PMID- 24459724
TI  - Histone variants and epigenetic inheritance.
AB  - Nucleosome particles, which are composed of core histones and DNA, are the basic
      unit of eukaryotic chromatin. Histone modifications and histone composition
      determine the structure and function of the chromatin; this genome packaging,
      often referred to as "epigenetic information", provides additional information
      beyond the underlying genomic sequence. The epigenetic information must be
      transmitted from mother cells to daughter cells during mitotic division to
      maintain the cell lineage identity and proper gene expression. However, the
      mechanisms responsible for mitotic epigenetic inheritance remain largely unknown.
      In this review, we focus on recent studies regarding histone variants and discuss
      the assembly pathways that may contribute to epigenetic inheritance. This article
      is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.

PMID- 24459725
TI  - Chaperoning the histone H3 family.
AB  - Chromatin is a highly dynamic nucleoprotein structure, which orchestrates all
      nuclear process from DNA replication to DNA repair, fromtranscription to
      recombination. The proper in vivo assembly of nucleosome, the basic repeating
      unit of chromatin, requires the deposition of two H3-H4 dimer pairs followed by
      the addition of two dimers of H2A and H2B. Histone chaperones are responsible for
      delivery of histones to the site of chromatin assembly and histone deposition
      onto DNA, histone exchange and removal. Distinct factors have been found
      associated with different histone H3 variants, which facilitate their deposition.
      Unraveling the mechanism of histone depositionby specific chaperones is of key
      importance to epigenetic regulation. In this review, we focus on histoneH3
      variants and their deposition mechanisms. This article is part of a Special Issue
      entitled: Histone chaperones and Chromatin assembly.

PMID- 24459726
TI  - All roads lead to chromatin: multiple pathways for histone deposition.
AB  - Chromatin, a complex of DNA and associated proteins, governs diverse processes
      including gene transcription, DNA replication and DNA repair. The fundamental
      unit of chromatin is the nucleosome, consisting of 147 bp of DNA wound about 1.6
      turns around a histone octamer of one (H3-H4)2 tetramer and two H2A-H2B dimers.
      In order to form nucleosomes, (H3-H4)2 tetramers are deposited first, followed by
      the rapid deposition of H2A-H2B. It is believed that the assembly of (H3-H4)2
      tetramers into nucleosomes is the rate-limiting step of nucleosome assembly.
      Moreover, assembly of H3-H4 into nucleosomes following DNA replication, DNA
      repair and gene transcription is likely to be a key step in the inheritance of
      epigenetic information and maintenance of genome integrity. In this review, we
      discuss how nucleosome assembly of H3-H4 is regulated by concerted actions of
      histone chaperones and modifications on newly synthesized H3 and H4. This article
      is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.

PMID- 24459723
TI  - Towards a mechanism for histone chaperones.
AB  - Histone chaperones can be broadly defined as histone-binding proteins that
      influence chromatin dynamics in an ATP-independent manner. Their existence
      reflects the importance of chromatin homeostasis and the unique and unusual
      biochemistry of the histone proteins. Histone supply and demand at chromatin is
      regulated by a network of structurally and functionally diverse histone
      chaperones. At the core of this network is a mechanistic variability that is only
      beginning to be appreciated. In this review, we highlight the challenges in
      determining histone chaperone mechanism and discuss possible mechanisms in the
      context of nucleosome thermodynamics. We discuss how histone chaperones prevent
      promiscuous histone interactions, and consider if this activity represents the
      full extent of histone chaperone function in governing chromatin dynamics. This
      article is part of a Special Issue entitled: Histone chaperones and Chromatin
      assembly.

PMID- 24459727
TI  - The role of FACT in making and breaking nucleosomes.
AB  - FACT is a roughly 180 kDa heterodimeric protein complex important for managing
      the properties of chromatin in eukaryotic cells. Chromatin is a repressive
      barrier that plays an important role in protecting genomic DNA and regulating
      access to it. This barrier must be temporarily removed during transcription,
      replication, and repair, but it also must be rapidly restored to the original
      state afterwards. Further, the properties of chromatin are dynamic and must be
      adjusted as conditions dictate. FACT was identified as a factor that destabilizes
      nucleosomes in vitro, but it has now also been implicated as a central factor in
      the deposition of histones to form nucleosomes, as an exchange factor that swaps
      the histones within existing nucleosomes for variant forms, and as a tether that
      prevents histones from being displaced by the passage of RNA polymerases during
      transcription. FACT therefore plays central roles in building, maintaining,
      adjusting. and overcoming the chromatin barrier. This review summarizes recent
      results that have begun to reveal how FACT can promote what appear to be
      contradictory goals, using a simple set of binding activities to both enhance and
      diminish the stability of nucleosomes. This article is part of a Special Issue
      entitled: Histone chaperones and Chromatin assembly.

PMID- 24459728
TI  - Histone acetyltransferase 1: more than just an enzyme?
AB  - Histone acetyltransferase 1 (HAT1) is an enzyme that is likely to be responsible
      for the acetylation that occurs on lysines 5 and 12 of the NH2-terminal tail of
      newly synthesized histone H4. Initial studies suggested that, despite its
      evolutionary conservation, this modification of new histone H4 played only a
      minor role in chromatin assembly. However, a number of recent studies have
      brought into focus the important role of both this modification and HAT1 in
      histone dynamics. Surprisingly, the function of HAT1 in chromatin assembly may
      extend beyond just its catalytic activity to include its role as a major histone
      binding protein. These results are incorporated into a model for the function of
      HAT1 in histone deposition and chromatin assembly. This article is part of a
      Special issue entitled: Histone chaperones and Chromatin assembly.

PMID- 24459729
TI  - A global requirement for the HIR complex in the assembly of chromatin.
AB  - Due to its extensive length, DNA is packaged into a protective chromatin
      structure known as the nucleosome. In order to carry out various cellular
      functions, nucleosomes must be disassembled, allowing access to the underlying
      DNA, and subsequently reassembled on completion of these processes. The assembly
      and disassembly of nucleosomes is dependent on the function of histone modifiers,
      chromatin remodelers and histone chaperones. In this review, we discuss the roles
      of an evolutionarily conserved histone chaperone known as the HIR/HIRA complex.
      In S. cerevisiae, the HIR complex is made up of the proteins Hir1, Hir2, Hir3 and
      Hpc2, which collectively act in transcriptional regulation, elongation, gene
      silencing, cellular senescence and even aging. This review presents an overview
      of the role of the HIR complex, in yeast as well as other organisms, in each of
      these processes, in order to give a better understanding of how nucleosome
      assembly is imperative for cellular homeostasis and genomic integrity. This
      article is part of a Special Issue entitled: Histone chaperones and Chromatin
      assembly.

PMID- 24459730
TI  - Histone chaperones link histone nuclear import and chromatin assembly.
AB  - Histone chaperones are proteins that shield histones from nonspecific
      interactions until they are assembled into chromatin. After their synthesis in
      the cytoplasm, histones are bound by different histone chaperones, subjected to a
      series of posttranslational modifications and imported into the nucleus. These
      evolutionarily conserved modifications, including acetylation and methylation,
      can occur in the cytoplasm, but their role in regulating import is not well
      understood. As part of histone import complexes, histone chaperones may serve to
      protect the histones during transport, or they may be using histones to promote
      their own nuclear localization. In addition, there is evidence that histone
      chaperones can play an active role in the import of histones. Histone chaperones
      have also been shown to regulate the localization of important chromatin
      modifying enzymes. This review is focused on the role histone chaperones play in
      the early biogenesis of histones, the distinct cytoplasmic subcomplexes in which
      histone chaperones have been found in both yeast and mammalian cells and the
      importins/karyopherins and nuclear localization signals that mediate the nuclear
      import of histones. We also address the role that histone chaperone localization
      plays in human disease. This article is part of a Special Issue entitled: Histone
      chaperones and chromatin assembly.

PMID- 24459731
TI  - Precise deposition of histone H2A.Z in chromatin for genome expression and
      maintenance.
AB  - Histone variant H2A.Z is essential in higher eukaryotes and has different
      functions in the cell. Several studies indicate that H2A.Z is found at specific
      loci in the genome such as regulatory-gene regions, where it poises genes for
      transcription. Itsdeposition creates chromatin regions with particular structural
      characteristics which could favor rapid transcription activation. This review
      focuses on the highly regulated mechanism of H2A.Z deposition in chromatin which
      is essential for genome integrity. Chaperones escort H2A.Z to large ATP-dependent
      chromatin remodeling enzymes which are responsible for its deposition/eviction.
      Over the last ten years, biochemical, genetic and genomic studies helped us
      understand the precise role of these complexes in this process. It hasbeen
      suggested that a cooperation occurs between histone acetyltransferase and
      chromatin remodeling activities to incorporate H2A.Z in chromatin. Its regulated
      deposition near centromeres and telomeres also shows its implication in
      chromosomal structure integrity and parallels a role in DNA damage response.
      Thedynamics of H2A.Z deposition/eviction at specific loci was shown to be
      critical for genome expression andmaintenance, thus cell fate. Altogether, recent
      findings reassert the importance of the regulated depositionof this histone
      variant. This article is part of a Special Issue entitled: Histone chaperones and
      Chromatin assembly.

PMID- 24459732
TI  - Cell cycle regulation of silent chromatin formation.
AB  - Identical genes in two different cells can stably exist in alternate
      transcriptional states despite the dynamic changes that will occur to chromatin
      at that locus throughout the cell cycle. In mammals, this is achieved through
      epigenetic processes that regulate key developmental transitions and ensure
      stable patterns of gene expression during growth and differentiation. The budding
      yeast Saccharomyces cerevisiae utilizes silencing to control the expression state
      of genes encoding key regulatory factors for determining cell-type, ribosomal RNA
      levels and proper telomere function. Here, we review the composition of silent
      chromatin in S. cerevisiae, how silent chromatin is influenced by chromatin
      assembly and histone modifications and highlight several observations that have
      contributed to our understanding of the interplay between silent chromatin
      formation and stability and the cell cycle. This article is part of a Special
      Issue entitled: Histone chaperones and Chromatin assembly.

PMID- 24459733
TI  - Centromeric chromatin and the pathway that drives its propagation.
AB  - The centromere is the locus that directs chromosomal inheritance at cell
      division. While centromeres in diverse eukaryotes are commonly found at sites of
      repetitive DNA, their location is epigenetically specified. The histone H3
      variant CENP-A is the prime candidate for epigenetically marking the centromere,
      and recent work has uncovered several additional proteins that play key roles in
      centromere assembly and maintenance. We describe advances in the identification
      and characterization of proteins that form the centromere, and focus on recent
      findings that have advanced our understanding of the assembly of functional
      centromeric chromatin. This article is part of a Special Issue entitled: Histone
      chaperones and chromatin assembly.

PMID- 24459734
TI  - Lessons from senescence: chromatin maintenance in non-proliferating cells.
AB  - Cellular senescence is an irreversible proliferation arrest, thought to
      contribute to tumor suppression, proper wound healing and, perhaps, tissue and
      organismal aging. Two classical tumor suppressors, p53 and pRB, control cell
      cycle arrest associated with senescence. Profound molecular changes occur in
      cells undergoing senescence. At the level of chromatin, for example, senescence
      associated heterochromatic foci (SAHF) form in some cell types. Chromatin is
      inherently dynamic and likely needs to be actively maintained to achieve a stable
      cell phenotype. In proliferating cells chromatin is maintained in conjunction
      with DNA replication, but how non-proliferating cells maintain chromatin
      structure is poorly understood. Some histone variants, such as H3.3 and macroH2A
      increase as cells undergo senescence, suggesting histone variants and their
      associated chaperones could be important in chromatin structure maintenance in
      senescent cells. Here, we discuss options available for senescent cells to
      maintain chromatin structure and the relative contribution of histone variants
      and chaperones in this process. This article is part ofa Special Issue entitled:
      Histone chaperones and chromatin assembly.

PMID- 24459736
TI  - Histone variants and chromatin assembly in plant abiotic stress responses.
AB  - Genome organization into nucleosomes and higher-order chromatin structures has
      profound implications for the regulation of gene expression, DNA replication and
      repair. The structure of chromatin can be remodeled by several mechanisms; among
      others, nucleosome assembly/disassembly and replacement of canonical histones
      with histone variants constitute important ones. In this review, we provide a
      brief description on the current knowledge about histone chaperones involved in
      nucleosome assembly/disassembly and histone variants in Arabidopsis thaliana. We
      discuss recent advances in revealing crucial functions of histone chaperones,
      nucleosome assembly/disassembly and histone variants in plant response to abiotic
      stresses. It appears that chromatin structure remodeling may provide a flexible,
      global and stable means for the regulation of gene transcription to help plants
      more effectively cope with environmental stresses. This article is part of a
      Special Issue entitled: Histone chaperones and chromatin assembly.

PMID- 24459737
TI  - Chromatin-mediated Candida albicans virulence.
AB  - Candida albicans is the most prevalent human fungal pathogen. To successfully
      propagate an infection, this organism relies on the ability to change morphology,
      express virulence-associated genes and resist DNA damage caused by the host
      immune system. Many of these events involve chromatin alterations that are
      crucial for virulence. This review will focus on the studies that have been
      conducted on how chromatin function affects pathogenicity of C. albicans and
      other fungi. This article is part of a Special Issue entitled: Histone chaperones
      and Chromatin assembly.

PMID- 24459735
TI  - Histone exchange and histone modifications during transcription and aging.
AB  - The organization of the eukaryotic genome into chromatin enables DNA to fit
      inside the nucleus while also regulating the access of proteins to the DNA to
      facilitate genomic functions such as transcription, replication and repair. The
      basic repeating unit of chromatin is the nucleosome, which includes 147 bp of DNA
      wrapped 1.65 times around an octamer of core histone proteins comprising two
      molecules each of H2A, H2B, H3 and H4. Each nucleosome is a highly stable unit,
      being maintained by over 120 direct protein-DNA interactions and several hundred
      water mediated ones. Accordingly, there is considerable interest in understanding
      how processive enzymes such as RNA polymerases manage to pass along the coding
      regions of our genes that are tightly packaged into arrays of nucleosomes. Here
      we present the current mechanistic understanding of this process and the evidence
      for profound changes in chromatin dynamics during aging. This article is part of
      a Special Issue entitled: Histone chaperones and Chromatin assembly.

PMID- 24459739
TI  - Surprised by joy: a journey through suffering.
AB  - Understanding suffering as possible meaning of cancer for patients and their
      families is a necessary part of cancer nursing care. Suffering occurs when the
      intactness or integrity of the individuals is threatened or disrupted (Cassel
      1999); the authors believe that exploring cancer patients' suffering is vital to
      improve patient quality care. This article discusses suffering as a feature for
      oncology patients at tertiary hospital in Jordan. We are aiming through
      understanding the three following narratives of cancer patients who experience
      and witness the suffer during their disease journey to illustrate how the
      suffering reflect their behavior and day to day life. The first case is a young
      man of 24 years old who was diagnosed with nasopharyngeal carcinoma five years
      ago, treated then relapsed and receiving palliative care up to moment, the
      narrative focus on his suffering from corrupted relations with his wife due to
      infected face wound and loss of the financial support. The Second case is a 38
      years old female who diagnosed with melanoma 15 years ago, she experience
      psychological suffering due to changes in her body image. She is taking care of
      motor handicapped husband in addition to her Kids. The Last case is a 54 years
      old female who had lung cancer. She is still fighting her disease. Consequently,
      she is suffering from the disease, cause to affect her job.We found out that
      their spirituality and beliefs system enables them to endure and fight their
      disease, alleviate suffering, enhance adaptation and redefine hope. The health
      care team who provide the care for these cases focus interdisciplinary team
      approach who affirm that the transcendental is there when disease and mute or
      expressive suffering are recognized together, they do the work of creating a full
      meaning for patients and families. Nurses play a crucial role in managing such
      cases .It is the core of nursing care to presence the mean of listening,
      touching, acknowledging, honoring patient's wishes and working within specialized
      multidisciplinary team, It is the greatness to be part of a team that being a
      huge circle surrounding patient with special demand and focusing on them in
      addition to their families rather than the disease itself aiming to assure best
      quality of life and to gain patients satisfaction. They recognize, assess and
      reassess patients' needs reframing of goals by educating, advocating,
      coordinating and supporting, with the major role in bereavement.

PMID- 24459738
TI  - The Urbachs of Vienna and Philadelphia.

PMID- 24459740
TI  - [Target validation strategy in designing novel therapeutics for schizophrenia].

PMID- 24459741
TI  - U.S. dental school applicants and enrollees, 2011 and 2012 entering classes.
AB  - This report examines the characteristics of dental school applicants and
      enrollees using data from the 2010-11 and 2011-12 application cycles of the
      American Dental Education Association's Associated American Dental Schools
      Application Service (ADEA AADSAS). The report presents data on the demographic
      composition and academic preparation of applicants, first-time enrollees, and
      total first-year enrollees during these two application cycles. The data indicate
      that the number of applicants has decreased modestly during this time, yet the
      number of first-time, first-year enrollees continues to rise mainly reflecting
      the opening of new dental schools and expansion of existing class sizes at some
      schools. Findings also indicate reduced gaps by gender in dental school
      applicants and enrollees. By contrast, the percentage of underrepresented
      minority applicants and enrollees increased only slightly. The results
      highlighted in this study have important implications for health professions
      education advisors, dental educators, and members of the broader dental education
      community.

PMID- 24459742
TI  - [Thoughts on development of pharmaceutical drugs].

PMID- 24459743
TI  - Evidence- based practice.

PMID- 24459744
TI  - Improving value in health care through practical steps.

PMID- 24459745
TI  - Heart disease.

PMID- 24459746
TI  - Heart disease--reply.

PMID- 24459747
TI  - On dental caries and dental erosion in Swedish young adults.
AB  - BACKGROUND: All children in Sweden are entitled to regular, free dental care up
      to 20 years of age. While dental caries generally continues to decline, still
      there is a pronounced skewness in caries prevalence. Furthermore, the reported
      increase in dental erosion in young adults is cause for concern. AIM: The aim was
      to study the prevalence of dental caries and dental erosion in a cohort of
      Swedish 20 year-olds, with special reference to the influence of previous caries
      experience and lifestyle as well as parental, socioeconomic and psychosocial
      factors. MATERIAL AND METHODS: The study was prospective, longitudinal and cross
      sectional in design and based on registration of caries lesions, dental erosion,
      body adiposity status, saliva sampling, interviews, and questionnaires at 20
      years of age. Data were available for the same cohort at 1, 3, 6 and 15 years of
      age. 499 subjects (74 percent of the original cohort) were included. Five
      individuals were subsequently excluded, leaving a final sample of 494. RESULTS:
      74 percent of the subjects had initial and/or manifest caries lesions and/or
      restorations. The mean number of DimFS was 5.8 and the mean number of DmFS on
      occlusal surfaces of molars was 1.1. There was a strong relationship between
      caries activity at 3 and 6 years of age and approximal caries prevalence in
      premolars and molars at 20 years of age. Overweight/obese individuals had
      significantly higher caries prevalence than normal weight individuals. Parental,
      socioeconomic and psychosocial factors during infancy were related to approximal
      caries at age 20. Dental erosion was found in 75 percent of the individuals: 18
      percent of these had extensive erosion. There was a significant association
      between caries and dental erosion. A relationship was found between dental
      erosion and lifestyle factors and overweight/obesity. CONCLUSIONS: There is a
      strong relationship between caries prevalence at age 20 and caries experience in
      early childhood. Young adults show a high prevalence of dental erosion, but the
      severity is generally low. Overweight and obese individuals have more caries than
      normal weight individuals. Parental influence during the formative years has an
      impact on caries prevalence in young adulthood. In this cohort, dental caries and
      dental erosion at age 20 are related to overweight/obesity and lifestyle factors.

PMID- 24459748
TI  - [Yolillales, the forgotten wetlands. Preface].

PMID- 24459749
TI  - [Wetlands dominated by palms (Arecaceae), emphasis in those in the New World].
AB  - It is well known that most forests in humid tropical lowlands are species rich,
      and the popular view is that most species are represented by only a few
      individuals. Despite this common understanding of high richness and low species
      dominance, within humid tropical regions there are extensive forested ecosystems
      composed by only few species. These nearly monospecific forests usually occupy
      poorly drained soils and, except for the mangroves, are quite understudied. In
      this paper, I review the literature and my own field notes on more than three
      years studying the structure of palm swamps in Caribbean Costa Rica and Florida
      to describe some of the major vegetation associations in wetlands dominated by
      palm species in the Neotropical Region, although I also include some information
      about similar systems in the Old World Tropics. I mention the most abundant
      species that compose those palm dominated swamps and -whenever possible- describe
      forest structure, known distribution, and uses.

PMID- 24459750
TI  - [Distribution, surface and protected area of palm-swamps in Costa Rica and
      Nicaragua].
AB  - In Central America, palm swamps are known collectively as yolillales. These
      wetlands are usually dominated by the raffia palm Raphia taedigera, but also by
      the royal palm Manicaria saccifera and -in lower extensions- by the American oil
      palm Elaeis oleifera. The yolillales tend to be poor in woody species and are
      characteristic of regions with high rainfall and extensive hydroperiods, so they
      remain flooded most of the year. The dominance of large raffia palm leaves in the
      canopy, allow these environments to be distinguishable in aerial photographs,
      which consequently has helped to map them along most of their distribution.
      However, while maps depicting yolillales are available, the extent of their
      surface area, perimeter and connectivity remains poorly understood. This is
      particularly true for yolillales in Costa Rica and Nicaragua, countries that
      share a good proportion of palm dominated swaps in the Rio San Juan Basin. In
      addition, it is not known the actual area of these environments that is under any
      category of protection according to the conservation systems of both countries.
      As a first step to catalog yolillal wetlands in Costa Rica and Nicaragua, this
      paper evaluates cartographic maps to delineate yolillales in the region. A
      subsample of yolillales mapped in this study were visited and we geo-referenced
      them and evaluate the extent and condition of the swamp. A total of 110 883.2ha
      are classified as yolillales in Nicaragua, equivalent to 22% of wetland surface
      area recorded for that country (excluding the Cocibolca and Xolothn Lakes). In
      Costa Rica, 53 931.3ha are covered by these palm dominated swamps, which
      represent 16.24% of the total surface area covered by wetlands. About 47% of the
      area covered by yolillales in Nicaragua is under some category of protection, the
      largest extensions protected by Cerro Silva, Laguna Tale Sulumas and Indio Maiz
      Nature Reserves. In Costa Rica, 55.5% of the area covered by yolillal is located
      within protected areas, mainly the Tortuguero National Park, Barra del Colorado
      Wildlife Refuge and the Sierpe-Thrraba National Wetland. Therefore, in both
      countries, about half the area covered by these wetlands is not protected by
      their systems of protection of wilderness areas.

PMID- 24459751
TI  - [Phenology and growth of Raphia taedigera (Arecaceae) in northeastern Costa Rica
      wetlands].
AB  - Here, I describe phenological activity of the raffia palm Raphia taedigera that
      dominates coastal swamps in northeastern Costa Rica. In this species,
      reproduction extends through the whole year, and it starts with the emergence and
      development of new inflorescences through the first month of the cycle. Expanded
      inflorescences develop into open flowers in a process that extends for three to
      four weeks to give rise to small fruits that are evidenced a month later. During
      the next twelve months or so, fruits mature but it take around six more months
      for all fruits to fall from the tree. Therefore, the entire reproductive process
      may exceed over two years. Different from other palm species, reproductive events
      in R. taedigera are aseasonal, and it is possible to observe palms in any
      reproductive state the whole year. Although the long period to fruit maturity
      exposes the seed to predispersal losses, this disadvantage may be over weighted
      by the production of large and heavy seeds that mature at different times on the
      same inflorescence.

PMID- 24459752
TI  - [Seed germination and seedling survival and growth in swamps dominated by palms
      Raphia tae- digera (Arecaceae) in Tortuguero plains, Costa Rica].
AB  - In the marshes dominated by palms, seeds face anaerobic substrates and long
      flooding periods. Some tree species are capable of growing both in flooded swamps
      and in areas with lower influence of the flood. I studied the potential
      settlement of various tree species in different macrohabitats in the Tortuguero
      floodplain using three experiments: (1) Manicaria saccifera and Raphia taedigera
      seed germination in palm-swamps and forests of slopes; (2) germination of R.
      taedigera seeds along a microtopographic gradient; and (3) seed germination and
      seedling height growth of six woody species (Dipteryx oleifera, Pterocarpus
      officinalis, Prioria copaifera, Pentaclethra macroloba, Carapa guianensis and
      Crudia acuminata) and two palms (R. taedigera and Manicaria saccifera) under
      different forest and swamp habitats. In the first experiment, I found that the
      palms germinated much earlier in the slope forest than in the palm-swamp. In the
      second experiment, in drier plots (less effect of flooding) germination began
      earlier than in the more humid plots. In the third experiment, woody species
      germinated faster than the studied palms, and some species do not tolerate
      flooded areas (marshes and swamps), so they cannot germinate or survive in them.
      Other woody species were removed from the slope forest, probably due to seed
      predators. Based on the presence or absence of these species in the environment
      of study were divided into: (1) obliged swamp species (R. taedigera and M
      saccifera), (2) swamp intolerant (D. oleifera), and (3) facultative wetland
      species (P officinalis, P copaifera, P macroloba, C. guianensis). Crudia
      acuminata does not seem to follow any of these categories.

PMID- 24459753
TI  - [Predation, removal and seed dispersal in a wetland dominated by palms
      (Arecaceae)].
AB  - In the Tortuguero floodplains, Costa Rica, a significant number of trees such as
      Carapa guianensis, Pentaclethra mnacroloba and the palm Manicaria saccifera have
      floating seeds adapted to hydrocory, while others, such as the almendro Dipteryx
      oleifera and the raffia palm Raphia taedigera have heavy seeds that do not float.
      These species have differential distributions, and while C. guianensis, P
      macroloba and D. oleifera also grow on slopes away from the flood, the palms M
      saccifera and R. taedigera hardly occur outside the swamps, where they stand as
      the dominant species. To understand the differences in the micro-distribution of
      these tree species in waterlogged environments and differences in their seed
      adaptations, I did a series of experiments to compare the loss and germination of
      their seeds in the slope forest and in palm swamps in the region. Overall, seeds
      in the forest slope have higher removal rates than those in the M. saccifera and
      R. taedigera swamps. This last one exhibits the lowest seed loss of all three
      habitats. Also, differences in seed predation/removal were noticed between the
      two species of palms studied. Thus, seeds of M saccifera disappeared rapidly,
      regardless of density aggregation and location in the swamp. Removal rates in R.
      taedigera seeds were low in the raffia dominated swamp, where apparently, seed
      losses are slightly higher in the mounds of palm clumps than in the swamp floor.
      These observations suggest that both: flooding and microtopography determine,
      directly or indirectly, the fate of tree species within these wetlands.
      Restrictions on seed dispersal and the slow germination confine R. taedigera
      marshes and flooded places, whereas flooding and predators mediate in the
      distribution of the other tree species.

PMID- 24459754
TI  - [Litter production and breakdown in swamps dominated by palms (Arecaceae) in
      northeastern Costa Rica].
AB  - In Raffia (Raphia taedigera) palm-swamps, it is frequent to observe high mounds
      at the base of the palm clumps. These mounds are formed by the accumulation of
      litter and organic matter, or might result from upturned roots of wind-thrown
      trees. The mounds serve as anchorage site for the palms, and could be important
      for the establishment of woody tree species in the swamp. The formation of these
      mounds might be explained by the unequal accumulation of organic matter in the
      wetland, or by differences in decomposition rates between Raffia litter versus
      the litter produced in adjacent mixed forests. To distinguish between these
      hypotheses, I compared the spatial distribution of litter in a R. taedigera swamp
      with the litter distribution on an adjacent slope forest, where litter
      distribution is expected to be homogeneous. In addition, I compared decomposition
      rates of major components of fine litter in three different environments: two
      wetlands dominated by palms (R. taedigera and Manicaria saccifera) and a slope
      forest that experiences lower inundation effects. On the palm swamp, noticeable
      concentration of litter was observed near the bases of clumps of palm as opposed
      to the swamp floor. In the adjacent slope forest, the magnitude of the
      differences in the distribution of litter is small and there is no accumulation
      at the base of emergent trees. It was also found that litter production increases
      during heavy rains and storms that follow dry periods. The swamp environment,
      independent of the litter, showed significantly lower decomposition rates than
      the surrounding forest slope. Furthermore, R. taedigera litter decomposes as fast
      as the slope forest litter. Overall, these results suggest that resistance to
      decomposition is not a major factor in the formation of mounds at the bases of R.
      taedigera clumps. Instead, litter accumulation contributes to the formation of
      the mounds that rise above the surface of the swamp.

PMID- 24459755
TI  - [Preliminary plant inventory of the palm-swamps in the Caribbean of Costa Rica
      and Nicaragua].
AB  - In the Caribbean slope of Isthmian Central America, plant associations dominated
      by the palms Raphia taedigera and Manicaria saccifera develop in poorly drained
      or waterlogged soils. These associations are known locally as yolillales or palm
      swamps, although there are differences in the forest structure and plant
      diversity associated with both palm species. In this paper, we report the results
      of a preliminary inventory of tree species found in eight palm-swamps at five
      locations in southeastern Nicaragua and northeastern Costa Rica. Our data reveal
      low tree diversity in these swamps with only 60 species accounted in them. This
      figure is equivalent to close to 8% of the plant species known for this region.
      In general, R. taedigera dominates flooded areas with extensive hydroperiods and
      lower floristic diversity, while M. saccifera is often found in flooded forests
      with more structure and diversity.

PMID- 24459756
TI  - [Annotated list of the plants of the Tortuguero National Park].
AB  - The floodplains of Tortuguero, in northeastern Costa Rica, stand as one of the
      richest plant-species regions in Central America. In this paper, we present the
      annotated check-list of vascular plants that are present within the rainforest of
      Tortuguero National Park (TNP), a 26 604h land that protects most of the
      biological diversity of these plains. Our list resulted from collections made in
      2012, as well as the examination of material mantained at the Herbarium of the
      National Biodiversity Institute of Costa Rica, INBio (ATTA Database) and in the
      TROPICOS database. A total of 732 vascular plant species included in 413 genera
      are known to the Park. Two of these species have limited distributions and are
      endemic to Costa Rica: Pseuderanthemum pittieri (Acanthaceae) and Paullinia
      austin-smithii (Sapindaceae). Ninety species have known ethnobotanical uses. The
      high diversity in plant species reported here for the forest environments of
      Tortuguero contrasts with the low species diversity previously reported in the
      palm-swamps that characterize the riverine habitats within the Park.

PMID- 24459757
TI  - [The Raffia-swamps as sources or sinks of avifauna: a first approach to the
      problem].
AB  - In the Tortuguero region, northeastern Costa Rica, tropical forests are home to
      over 300 species of birds. Within this ecosystem, wetlands dominated by the
      raffia palm Raphia taedigera and the royal palm Manicaria saccifera extend in
      large monospecific swamps locally known as yolillales. These wetlands are
      characterized by low plant diversity, simple structure, waterlogged soils, and
      extended hydroperiod. There is hardly any information on the bird communities
      that inhabit or uses yolillales. We describe this omitofauna, comparing the
      species that inhabit the palm-swams and in the adjacent forest in terms of
      species richness and diversity. During October-November 2008, we used transects
      and hearing stations in both habitats in four locations in the region. We located
      a total of 11 bird species in the palm-swamps and 31 in the adjacent forests. Our
      observations suggest that palm-swamps have lower species richness than adjacent
      forests and that these environments also differ in species composition. Despite
      their low diversity, yolillales are employed by species with different degrees of
      vulnerability, so that they may be important for bird conservation in the region.
      Sampling in yolillales is very hard, so our data should be considered
      preliminary. Further efforts in these environments are needed to improve our
      knowledge on the bird community that uses them.

PMID- 24459758
TI  - [Amphibians and reptiles in the swamps dominated by the palm Raphia taedigera
      (Arecaceae) in northeastern Costa Rica].
AB  - The herpetofauna that inhabits Caribbean Costa Rica has received considerable
      attention in the last two decades. This assemblage includes a total of 141
      species of reptiles and 95 amphibians mostly distributed in tropical wet and
      moist lowland forests. While most information available came from primary and
      secondary forest sites, little is known about the amphibians and reptiles that
      inhabit more open habitats, such as wetlands and swamps. For instances, swaps
      dominated by the yolillo palm Raphia taedigera extend through much of the
      northeastern Caribbean coast of Costa Rica and eastern Nicaragua, but information
      about the herpetological community that uses such environments remains
      practically unknown. This situation reflects the little research conducted in
      such inhospitable environments. Here, we report the results of an intensive
      survey conducted to assess the herpetological community that inhabit R. taedigera
      palm-swamps. A total of 14 species of amphibians and 17 of reptiles have been
      recorded from these swamps. Amphibians and reptiles that inhabit yolillo swamps
      have wide distributions along much of Middle America and are considered common
      species throughout their range. In general, yolillo swamps are poor environments
      for herpetofauna: richness of reptiles and amphibians is almost two times higher
      in the adjacent forest than in the palm dominated swamps. Furthermore, most
      species observed in this swamps can be considered habitat generalists that are
      well adapted to the extreme conditions imposed by the changes in hydroperiods,
      reduce understory cover, low tree diversity and simple forest architecture of
      these environments. Despite similarities in the herpetofauna, it is clear that
      not all forest species use yolillo habitat, a characteristic that is discussed in
      terms of physical stress driven by the prolonged hydroperiod and reduced
      leaflitter in the ground, as these features drive habitat structure and
      herpetofaunal complexity. Our list of species using yolillo swamps is not
      definitive, and is likely to grow as more studies are conducted in this
      unexplored environment.

PMID- 24459759
TI  - [Use and conservation of palm swamps Raphia taedigera (Arecaceae) in the Area de
      Conservacion Tortuguero, Costa Rica].
AB  - The swamps dominated by raffia palm Raphia taedigera are conspicuous environments
      in the Tortuguero floodplains and in other wet regions along the Caribbean and
      Pacific coasts of Costa Rica. However, these environments have been little
      studied and are exposed to numerous threats, most importantly their replacement
      by agricultural activities or pastureland. In this paper, we describe some
      applications and uses of the raffia palms and other palms that are common in
      these flooded swamps. We also describe the efforts that have been made in Costa
      Rica for the protection or raffia-dominated swamps, through the environmental law
      frame of the country and the establishment of a protection system based on
      wilderness areas under different categories of protection. We discuss issues
      relevant to the future of these environments in the regions where they are
      distributed.

PMID- 24459760
TI  - Advantages of transanal hemorrhoidal dearterialization as compared to other
      surgical techniques for the treatment of hemorrhoidal disease.
AB  - Transanal hemorrhoidal dearterialization (THD) is a new surgical technique used
      for the treatment of hemorrhoidal disease. It is known for its easy performance
      and low perioperative risk. 44 patients have been operated by this method at the
      Clinic of General, Liver and Pancreatic Surgery for a period of 22 months. A
      comparative analysis was performed between the postoperative results with the use
      of transanal hemorrhoidal dearterialization, modified hemorrhoidectomy of
      Milligan-Morgan, and Whitehead's hemorrhoidectomy. CONCLUSIONS: When comparing
      transanal hemorrhoidal dearterialization with other methods, we found that it has
      an excellent aesthetic effect, requires shorter hospital stay and less
      analgesics, and causes less discomfort in the postoperative period.

PMID- 24459761
TI  - Diagnosis of liver hemangioma.
AB  - BACKGROUND: Benign liver tumors are now being diagnosed frequently with the
      advent of the greater use of imaging investigations. The most common lesion is
      the liver hemangioma 0.4-7.3%, with an incidence rate at autopsy ranging from 3%
      to 20%. MATERIAL AND METHODS: One hundred and one patients underwent operative
      treatment in the Department of General and Liver-pancreatic Surgery, UH
      "Alexandrovska" Sofia from 1995 to April 2013. There were 74 (73.3%) females and
      27 (26.7%) males. Mean age was 50.7 years (range 25 to 77). Seventy-four patients
      (73.3%) had a solitary tumor. Methods for diagnosis included history of the
      disease, routine haematological and liver function tests, ultrasonography, CT,
      MRI or a combination of more than one technique. RESULTS: The diagnostic
      sensitivity of the imaging procedures was U/S 96.9%, CT scanning 98.3% and MRI
      100% .The diagnostic specificity--U/S 60.3%, CT scanning 55.0%, MRI 85.7%.
      CONCLUSION: Hepatic hemangioma is diagnosed in most patients using non-invasive
      studies such as US, CT and MRI or a combination of them.

PMID- 24459762
TI  - Minimally invasive approach to thyroid gland surgery--indications, methods, first
      results.
AB  - After the introduction of minimally invasive operative techniques in the surgery
      of organs located in body cavities, extensive work has been done in the last five
      years with respect to their application in thyroid gland surgery as well.
      MATERIALS AND METHODS: In 2011, 406 patients underwent thyroid surgery at the
      Department of Surgery, Kaspela General Hospital for Active Treatment EOOD -
      Plovdiv. The study involved 48 of these patients, chosen at random and divided
      into two groups (A-minimally invasive thyroidectomy (MIT) - 26 patients, and B -
      minimally invasive video-assisted thyroidectomy (MIVAT) - 22 patients). All
      patients included in the study were selected on the basis of presence of one or
      more indeterminate nodules (fine needle aspiration biopsy - FNAB) sized up to 3.5
      cm, with normal size of the thyroid gland up to 20-25 cm2, detected by
      preoperative ultrasonography. The study excluded patients with recurrent goitre,
      malignant disease of the thyroid gland and evidence of preoperative radiation
      therapy in the area of the head, neck and/or upper mediastinum. The preoperative
      investigation included history, physical examination, blood indices, echography,
      gamma camera and FNAB. Sensation of pain was evaluated by the patients according
      to a visual analogue scale, where lack of pain was evaluated as 0, and the most
      severe pain was evaluated as 10. RESULTS: The average duration of the
      hospitalization of patients undergoing MIT was 16 +/- 3.14 hours, whereas the
      patients undergoing MIVAT had to stay at the hospital for 18 +/- 3.56 hours. No
      complications were registered regarding the recurrent laryngeal nerves (RLN), as
      well as the operative wound. It should be noted that in all patients the course
      of the respective RLN was identified during the operative intervention, visually
      in most cases, or by electrostimulation. Postoperative hypoparathyroidism,
      registered by measuring the level of serum calcium, was observed in one visual
      analogue scale, as well as in the administration of pain-relieving agents during
      hospitalization. Other complications were not registered for the follow-up
      period, which covered an average of 6.56 +/- 3.14 months. CONCLUSIONS: The
      clinical analysis of the patients observed gave us grounds to draw the following
      conclusions: 1. The minimally invasive approach in patients with thyroid gland
      pathology is a possible and favourable option in selected patients with size of
      the gland within certain limits and not suffering from severe concomitant
      diseases. 2. The results in both groups of patients were comparable and did not
      show significant difference.

PMID- 24459763
TI  - Diagnosis of spontaneous and secondary bacterial peritonitis in patients with
      hepatic cirrhosis and ascites.
AB  - Spontaneous bacterial peritonitis (SBP) is an infection that is not caused by
      intra-abdominal source requiring surgery. Nowadays SBP is the main cause of death
      in patients with cirrhosis. Treatment is carried out with third generation
      cephalosporins and albumin infusions. The aim of the study is to identify
      patients with SBP and to be distinguished from the cases with secondary bacterial
      peritonitis (SecBP) in patients with cirrhosis and ascites. We studied 167
      patients with cirrhosis and ascites and SBP was observed in 25 of them, while
      SecBP--in 22. The diagnosis of SBP is set in neutrophilic leukocytes in ascites >
      or = 250 cells/mm3 as bacterial cultures are positive in only 16% of them.
      Completely asymptomatic course had 16% of patients with SBP. Diagnosis of SecBP
      (according to Runyon's criteria) is based on increased total protein in ascitic
      fluid > 10 g/l (in 63.7% of patients > 30 g/l), elevated lactate dehydrogenase in
      ascites (LDH is > 240 U/l in all patients) and glucose < 2,7 mmol/l (only 4.5% of
      cases with secondary bacterial peritonitis). In support of SecBP are the
      polymicrobial flora, the isolation of anaerobes, enterococci, fungi, and the very
      high number of neutrophilic leukocytes in the peritoneal effusion and the
      refractoriness from conservative treatment. The examination of ascites with
      Multistix is more informative in secondary than in spontaneous bacterial
      peritonitis. In suspected secondary bacterial peritonitis CT is indicated.

PMID- 24459764
TI  - Comparative analysis of the four-port and three-port trocar access of the
      conventional laparoscopic cholecystectomy--review of the literature.
AB  - INTRODUCTION: The presented analysis focuses on the first stage in the
      development of the laparoscopic technique forsurgical removal of the gall
      bladder. The scope of the study starts with the period of its introduction in the
      clinical practice of the laparoscopic cholecystectomy and ends with the
      recognition of the three-port technique for surgical intervention. AIM: The aim
      of this analysis is to review the studies, focused on the indications applying
      different techniques of conventional laparoscopiccholecystectomy, to summarize
      their advantages and disadvantages and to pinpoint the future guidelinesfor the
      development of the surgical techniques. METHODOLOGIES AND MATERIALS: The studies
      of the decision making process for applying a certain surgical technique of the
      conventional laparoscopic cholecystectomy, the individualized approach in
      surgical treatment and the risks and complications in different methodologies
      were reviewed. The different aspects of the process were analyzed and to
      demonstrate their relevance, have been illustrated by the published by 2011
      studies. RESULTS: The review of the literature spams over 40 articles, which
      compare the two main techniques for conventional laparoscopic cholecystectomy in
      the following parameters: safety of the technique, technical parameters of the
      surgical intervention as access facilitation, the number, the position and the
      size of the trocars, surgery duration, blood loss, postoperative pain, the
      duration of the hospitalization, the time needed for physical recuperation, short
      -term and long-term cosmetic results, esthetic satisfaction of the patient and
      medical and social effectiveness. The reviewed studies don't show a significant
      advantage of any of those two techniques. In terms of safety, the four-port
      trocar technique is considered better, but in short-term cosmetic results and
      esthetic satisfaction, the three-port trocar has more merit. CONCLUSION: The
      comparative analysis of the three-port and four-port trocar access of the
      conventional laparoscopic cholecystectomy shows a tendency in the development of
      low invasive techniques. The period this study has covered is limited due to the
      introduction of the one-port techniques as a new direction in the development of
      the laparoscopic surgery and the shift in the focus from conventional
      laparoscopic techniques to techniques with a single access. The new tendencies in
      the low invasive techniques will be the subject of part 2.

PMID- 24459766
TI  - Surgical strategy for patients undergoing carotid endarterectomy.
AB  - Carotid endarterectomy (CEA) is a surgical intervention that aims to reduce
      neurological symptoms in carotid atherosclerosis and prevent brain damage and
      subsequent permanent neurological deficit. AIM: To study the major risk factors,
      surgical techniques, applied diagnostic methods and perioperative complications
      occurred in patients undergoing CEA. MATERIALS AND METHODS: 496 surgical
      interventions on the occasion of stenosis and/or occlusions of the carotid
      arteries were performed for the period 1987-2009 at the department of Vascular
      Surgery and Angiology of "St. Ekaterina"- University Hospital - Sofia. All
      patients were operated using standard access under general or local anaesthesia.
      During surgeries, the evaluation of cerebral hemodynamics and function was
      performed by transcranial Doppler Ultrasound (TCD) and cerebral oximetry (CO).
      Carotid shunting was selectively applied in cases of deterioration of the values
      of CO and TCD during cross clamping of the carotid arteries. RESULTS: With the
      highest relative share among cerebrovascular complications was stroke with 2.7%
      share in the group of asymptomatic patients and 1.7%--in the symptomatic group.
      When considering the other types of complications with the largest relative share
      were cardiac complications in both groups of patients--hemodynamic disorders and
      myocardial infarction. CONCLUSION: Low values of postoperative mortality and
      stroke after CEA in our study are comparable with other leading centers, proving
      that CEA is safe and effective surgical procedure for stroke prevention in both
      symptomatic and asymptomatic patients. Accurate perioperative diagnostic allows a
      good approach for choosing the correct surgical strategy.

PMID- 24459765
TI  - Per magna-ovarian metastases from primary locally advanced colorectal cancer--a
      review of the literature with a description of three clinical cases.
AB  - Krukenberg tumor is defined as metastatic lesions of gastrointestinal cancers.
      Several specific immunohistochemical methods can identify the main focus of
      malignant neoplasm. Ovarian metastases from colorectal cancer are rarely seen
      phenomenon. The authors examine in detail the literature on this issue and
      describe three own clinical cases of metachronous ovarian meta lesions in women
      undergoing surgery for locally advanced colorectal cancer--two of these
      metastases are unilateral, while one--bilateral established in a short time
      interval despite the casuistic nature of the pathology. One of the patients died
      in the early postoperative period of co-morbid complications unrelated to the
      underlying disease, and the other two monitoring continues during the adjuvant.
      Krukenberg-metastases from colorectal cancer occur in the blood-vascular pattern
      in time without damage to the left or right ovary. Metachronous development and
      operative treatment of ovarian metastases is far better prognosis of the cases
      with and operated simultaneously established metastases in the ovaries.

PMID- 24459767
TI  - Terpenes from Artemisia herba-alba.
AB  - Chromatographic investigation of the methylene chloride/methanol extract of the
      aerial parts of Artemisia herba-alba afforded a new monoterpene dimer, in
      addition to a known monoterpene and three known sesquiterpene lactones. The
      structures of the compounds were determined by comprehensive NMR analyses,
      including DEPT, COSY, HMQC, HMBC, and HRMS.

PMID- 24459768
TI  - Black tea supplementation improves antioxidant status in rats subjected to
      oxidative stress.
AB  - The protective effect of black tea extract (BTE) against HgCl2-induced oxidative
      damage in Wistar rats was investigated. Rats were injected with HgCl2 (5 mg/kg
      body weight in 0.9% NaCl) to induce oxidative stress. The aqueous BTE (2.5%) was
      prepared from CTC (curl, tear, crush) grade tea. BTE was fed to control and HgCl2
      treated rats by gavage at a dose of 1 ml/(100 g body weight d). Biomarkers of
      oxidative stress, such as the erythrocyte plasma membrane redox system (PMRS)
      activity, lipid peroxidation, and advanced oxidation protein products (AOPP),
      increased by 166, 31, and 373%, respectively, in response to HgCl2 treatment,
      while intracellular glutathione and plasma antioxidant potential, i.e. ferric
      reducing ability (FRAP) decreased by 75 and 22%, respectively. BTE protected the
      rats against HgCl2-induced oxidative damage and raised the antioxidant potential
      in control rats. Due to its strong antioxidant effect in vivo, black tea intake
      may provide a significant health-promoting effect to humans.

PMID- 24459769
TI  - Hepatitis C virus NS3-NS4A protease inhibitors from the endophytic Penicillium
      chrysogenum isolated from the red alga Liagora viscida.
AB  - Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV
      agents because of its important role in replication. In this work, we
      demonstrated that the ethyl acetate extract of the endophytic fungus Penicillium
      chrysogenum exhibited a potent activity against HCV NS3-NS4A protease with an
      IC50 value of 20 microg/ml. The fungus was isolated from the red alga Liagora
      viscida and identified by its morphology and 18S rDNA. Large-scale fermentation
      of the fungus in Czapek's peptone liquid medium followed by chromatographic
      purification of the active extract from the liquid medium allowed the isolation
      of twelve known metabolites. The biological properties of the isolated compounds
      were explored for anti-HCV protease as well as antimicrobial and anticancer
      activities. A computational docking study of the active isolated compounds
      against HCV protease was used to formulate a hypothetical mechanism for the
      inhibitory activity of the active compounds on the tested enzymes.

PMID- 24459770
TI  - Chemical constituents and cytotoxic effect of the main compounds of Lythrum
      salicaria L.
AB  - Lythrum salicaria L. (Lythraceae), a herbaceous plant growing widely in Iran, has
      been well known for many centuries for its astringent and styptic properties. A
      phytochemical investigation of this plant, based on spectroscopic analysis,
      identified fourteen compounds: 5-hydroxypyrrolidin-2-one (1), umbelliferone-6
      carboxylic acid (2), 3,3',4'-tri-O-methylellagic acid-4-O-beta-D-(2"-acetyl)
      glucopyranoside (3), 3,3',4'-tri-O-methylellagic acid-4-O-beta-D-glucopyranoside
      (4), daucosterol (5), phytol (6), dodecanoic acid (7), oleanolic acid (8),
      3,3',4'-tri-O-methylellagic acid (9), corosolic acid (10), beta-sitosterol (11),
      peucedanin (12), buntansin (13), and erythrodiol (14). All compounds, except for
      8 and 11, have been isolated from L. salicaria for the first time. Cytotoxic
      activities of the compounds were examined against three cancerous cell lines,
      colon carcinoma (HT-29), leukemia (K-562), and breast ductal carcinoma (T47D),
      and Swiss mouse embryo fibroblast (NIH-3T3) cells using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and
      methotrexate as positive control. Compounds 5, 10, 11, and 14 were the most
      active against the HT-29 cell line with IC50 values of 192.7, 36.8, 38.2, and
      12.8 microg/mL, respectively. Compounds 14, 11, 5, and 10 were 6.4, 2.8, 2.6, and
      1.4 times, respectively, more selective than methotrexate. Compound 5 was the
      most active against the K-562 cell line (IC50 = 50.2 microg/mL), with a
      selectivity exceeding that of methotrexate 13.3 times. The results of the
      cytotoxic assay confirmed that growth and proliferation of the cancer cell lines
      are predominantly influenced by triterpene derivatives and sterols of this plant.

PMID- 24459771
TI  - Development and validation of a high-performance liquid chromatography method for
      standardization of the bioactive ethyl acetate fraction of Alstonia scholaris
      (Linn.) R. Br. growing in Egypt.
AB  - Bio-guided fractionation of the ethanolic extract of the leaves of Alstonia
      scholaris (Apocynaceae) growing in Egypt was carried out to evaluate its
      antihyperglycemic activity in alloxan-induced diabetic rats and its
      hepatoprotective activity against CCl4-induced hepatotoxicity in rats. The ethyl
      acetate fraction of the ethanolic extract showed the highest antihyperglycemic
      [(133.6 +/- 4.2) mg/mL, relative to metformin with (92.3 +/- 2.7) mg/mL] and
      hepatoprotective [(37.9 +/- 1.4) U/L, relative to silymarin with (29.7 +/- 0.8)
      U/L] activities. Four compounds were isolated from this fraction, and identified
      by spectroscopic techniques and by comparison with reported data: caffeic acid
      and isoquercitrin for the first time from this plant, in addition to quercetin 3
      O-beta-D-xylopyranosyl (1''' --> 2")-beta-D-galactopyranoside (major compound)
      and chlorogenic acid. A validated reversed phase-high-performance liquid
      chromatography (RP-HPLC) method was developed for the standardization of the
      bioactive ethyl acetate fraction. The calibration curve showed good linearity (r2
      > 0.999) within tested ranges. The relative standard deviation of the method was
      less than 3% for intra- (0.4-2.0%) and inter-day (1.9-2.8%) assays. Mean recovery
      of the method was within the range of 98.5-102.5%. The minimum detectable
      concentration of the analyte (LOD) was found to be 0.04 microg/mL. This developed
      HPLC method was shown to be simple, rapid, precise, reproducible, robust,
      specific, and accurate for quality assessment of the bioactive fraction.

PMID- 24459772
TI  - Biodegradation of phenol by Antarctic strains of Aspergillus fumigatus.
AB  - Taxonomic identification of three newly isolated Antarctic fungal strains by
      their 18S rDNA sequences revealed their affiliation with Aspergillus fumigatus.
      Phenol (0.5 g/l) as the sole carbon source was completely degraded by all strains
      within less than two weeks. Intracellular activities of three key enzymes
      involved in the phenol catabolism were determined. Activities of phenol
      hydroxylase (EC 1.14.13.7), hydroquinone hydroxylase (EC 1.14.13.x), and catechol
      1,2-dioxygenase (EC 1.13.11.1) varied significantly between strains. The rates of
      phenol degradation in the three strains correlated best with the activity of
      catechol 1,2-dioxygenase. Six pairs of oligonucleotide primers were designed on
      the basis of the Aspergillus fumigatus Af293 genome sequence (NCBI Acc. No.
      XM_743491.1) and used to amplify phenol hydroxylase-related gene sequences. DNA
      sequences of about 1200 bp were amplified from all three strains and found to
      have a high degree of sequence identity with the corresponding gene of
      Aspergillus fumigatus Af293.

PMID- 24459773
TI  - Limitation of mitragynine biosynthesis in Mitragyna speciosa (Roxb.) Korth.
      through tryptamine availability.
AB  - Metabolite profiles of Mitragyna speciosa were determined by means of 1H NMR
      based and HPLC-based analyses. The results indicated that high contents of
      secologanin, caffeic acid, gallic acid, epigallocatechin, and mitragynine were
      accumulated in leaves. In M. speciosa, feedings of tryptamine, tryptophan,
      phenylalanine or tyrosine significantly increased the mitragynine contents.
      Feedings of tryptamine and loganin also enhanced the mitragynine accumulation,
      but feeding of loganin only did not affect the mitragynine level. The mRNA levels
      of anthranilate synthase alpha subunit (ASA), tryptophan decarboxylase (TDC), and
      strictosidine synthase (STR) were measured by quantitative real-time polymerase
      chain reaction (RT-qPCR) in control plants and those exposed to methyl jasmonate
      (MJ; 10 microM). All genes responded to MJ after a 24-h treatment. The
      mitragynine contents were also enhanced and corresponded to the transcript
      levels. From the present results we conclude that a high content of secologanin
      together with a undetectable level of tryptamine in M. speciosa feature the
      limitation of mitragynine biosynthesis. Additionally, expression of all the genes
      limits production of an essential precursor for mitragynine production.

PMID- 24459774
TI  - The cellular target specificity of pateamine A.
AB  - The natural product pateamine A (pateamine) from the sponge Mycale hentscheli is
      active against a wide range of dividing cells and has been shown to inhibit the
      functions of the eukaryotic initiation factor 4A (eIF4A). We have identified that
      pateamine is additionally able to modulate the formation of actin filaments and
      microtubules in vitro but at higher concentrations than required for inhibition
      of eIF4A. Cell cycle analysis confirmed that actin and tubulin are not major
      mediators of the cellular activity of pateamine. The range of targets identified
      demonstrates the value of multiple approaches to determining the mode of action
      of biologically active compounds.

PMID- 24459775
TI  - Female sex pheromone blends and male response of the legume pod borer, Maruca
      vitrata (Lepidoptera: Crambidae), in two populations of mainland China.
AB  - The legume pod borer, Maruca vitrata (Lepidoptera: Crambidae; syn. M.
      testulalis), is a serious pantropical insect pest of grain legumes. Comparative
      studies of M. vitrata female sex pheromone components in two different geographic
      populations in China, Wuhan and Huazhou, confirmed that (E,E)-10,12
      hexadecadienal (E10,E12-16:Ald) and (E)-10-hexadecenal (E10-16:Ald) were present
      in variable ratios in all pheromone gland extracts of both populations. (E,E)
      10,12-hexadecadienol (E10,E12-16:OH) was always detected in minor amounts using
      polar DB-WAX columns, but was never detected using medium-polar DB-17 columns for
      the two populations. E10-16:OH was not found in any of the M. vitrata sex
      pheromone gland extracts. The average ratios of E10-16:Ald, E10,E12-16:Ald, and
      E10,E12-16:OH in the pheromone gland extracts of populations from Wuhan and
      Huazhou were 79.5:100:12.1 and 10.3:100:0.7, respectively. Electrophysiological
      testing suggested that E10,E12-16:Ald elicited the highest male
      electroantennography (EAG) response, followed by E10,E12-16:OH and E10-16:Ald.
      Field-trapping tests with single synthetic sex pheromone lures showed that
      E10,E12-16:OH alone could not attract males, whereas E10,E12-16:Ald or E10-16:Ald
      alone attracted few males. Wuhan and Huazhou males were most attracted by lures
      containing E10-16:Ald + E10,E12-16:Ald + E10,E12-16:OH in doses of (80 + 100 +
      10) microg and (10 + 100 + 10) microg, respectively, per vial. Males could
      discriminate between the blends that were most attractive to their own geographic
      population and those that were most attractive to the reference population. Our
      findings suggest that geographic variation exists in the sex pheromone system of
      M. vitrata in China. The results are discussed with regard to the mechanisms
      underlying the sex pheromone variation.

PMID- 24459778
TI  - GMPs vs GCPs: manufacturing and compounding definitions.

PMID- 24459777
TI  - [National guidelines of diagnosis and treatment of the non-Hodgkin lymphoma].
AB  - Non-Hodgkin lymphoma comprises a heterogeneous group of haematological
      malignancies, classified according to their clinic, anatomic-pathological
      features and, lately, to their molecular biomarkers. Despite the therapeutic
      advances, nearly half of the patients will die because of this disease. The new
      diagnostic tools have been the cornerstone to design recent therapy targets,
      which must be included in the current treatment guidelines of this sort of
      neoplasms by means of clinical trials and evidence-based medicine. In the face of
      poor diagnoses devices in most of the Mexican hospitals, we recommend the present
      diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based
      on evidence. They include the latest and most innovative therapeutic approaches,
      as well as specific recommendations for hospitals with limited framework and
      therapy resources.

PMID- 24459779
TI  - Compounding pharmacies: before and after an inspection.
AB  - Recent events have directed the U.S. Food and Drug Administration's attention to
      compounding pharmacies and have increased the frequency and vigorousness of
      pharmacy inspections. It is critical for compounding pharmacists to be prepared
      for such inspections and to understand their responsibilities after an inspection
      is over.

PMID- 24459780
TI  - Preventing medication errors with nimodipine by compounding proper dosage forms.
AB  - Pharmacists can play an active role in preventing tragic medication errors by
      using United States Pharmacopeia standards, as well as other compounding
      guidelines, by using due diligence, and by following written standard operating
      procedures. Nimodipine is shown within this article as an example of the
      importance of proper dosing of a drug because, since the approval of nimodipine
      capsules in 1988, the U.S. Food and Drug Administration has identified 31 cases
      of medication errors associated with its use. Pharmacists can compound nimodipine
      oral suspension and prepare the doses in oral syringes for the nursing and
      medical staff.

PMID- 24459776
TI  - [National consensus of diagnosis and treatment of non-small cell lung cancer].
AB  - Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology,
      pathology, molecular biology, anesthesiology, algology, psychology, nutrition,
      and rehabilitation (all of them experts in lung cancer treatment) in order to
      develop the National Consensus on Lung Cancer. The consensus has been developed
      as an answer to the need of updated Mexican guidelines for the optimal treatment
      of the disease, as well as to the requirements that such guidelines be
      established by multidisciplinary panel, depicting the current attention given to
      cancer lung cases in Mexico. Thus, this paper analyses the epidemiological
      review, screening, diagnosis, staging, pathology, translational medicine, and the
      suitable therapies for early, locally advanced, and metastatic disease in the
      first, second, and third lines of management, as well as rehabilitation and
      palliative measures.

PMID- 24459781
TI  - Chemical penetration enhancers.
AB  - Chemical penetration enhancers are utilized in topical preparations as a method
      for enhancing permeation of drugs across the skin. In particular, they are
      utilized for transdermal delivery of medications in an attempt to produce a
      systemic response, to avoid first-pass metabolism, and to decrease the
      gastrointestinal transit time observed with oral medications. A review of the
      selection of chemical penetration enhancers, their mechanism of action, the most
      common chemical penetration enhancers in each class, and alternatives will be
      discussed in detail.

PMID- 24459782
TI  - 2013 State Compounding Legislation Tracker.

PMID- 24459783
TI  - Use of topical metronidazole in the treatment of anorectal Crohn's disease.
AB  - Anorectal Crohn's disease is one of the most problematic and debilitating forms
      of Crohn's disease. Crohn's disease is a type of inflammatory bowel disease that
      usually affects the intestines but may occur anywhere in the gastrointestinal
      tract and is frequently refractory to medication, which may ultimately result in
      proctocolectomy and ileostomy surgeries. It is reported in 3% to 5% of Crohn's
      patients and is found in conjunction with colorectal or enteric disease in one
      third to one-half of Crohn's disease patients. This article discusses the use of
      metronidazole 10% ointment for the treatment of anorectal Crohn's disease. Since
      metronidazole is not U.S. Food and Drug Administration approved for treating
      anorectal Crohn's disease, and there is no commercially available metronidazole
      10% ointment, compounding pharmacists can play a role in providing this dosage
      form. This article discusses some of the common symptoms of Crohn's disease and
      the use of topical metronidazole to treat the disease.

PMID- 24459784
TI  - Methocarbamol suspension for the treatment of rhabdomyolysis in equines.
AB  - Rhabdomyolysis in equines occurs in horses due to physical overexertion or
      underlying pathologic myopathy. Methocarbamol is a muscle relaxant that can be
      used in equines to treat symptoms associated with Rhabdomyolysis. Methocarbamol
      is available as a solution for injection but is not commercially available as an
      oral suspension. This article focuses on the treatment of Tying-up caused by
      overexertion, and details the treatment of Rhabdomyolysis with an oral suspension
      that was prepared for a veterinarian by a compounding pharmacist.

PMID- 24459785
TI  - Disguising the taste of antiretrovirals for pediatric patients infected with
      Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: creative flavor
      compounding and techniques, part 1.
AB  - The question of how to disguise the taste of antiretrovirals for pediatric
      patients infected with Human Immunodeficiency Virus/Acquired Immunodeficiency
      Syndrome is common for physicians, pharmacists, and parents/caregivers. Adherence
      to antiretroviral therapy is essential for living a long life and is imperative
      for the successful treatment of pediatric patients. The taste of these
      medications has been shown to affect adherence in this patient population.
      Parents/caregivers are not only tasked with remembering refills, dosages, and
      strengths of antiretrovirals, they have to become persuasive diplomats for the
      daily administration of these medications to their children. Provided in this
      first part of a two-part article is background information on this topic and a
      discussion on palatability concerns.

PMID- 24459786
TI  - Quality planning, part 1: a holistic and practical approach.
AB  - This article is the first in a two-part series that breaks down quality planning
      into a systematic, stepwise process. Part 1 addresses the tangible aspects of
      compounding that directly influence the quality of compounded preparations. Part
      2 will speak to less tangible but critically important mechanisms targeting
      continuous improvement. The author takes a holistic approach, which he describes
      as a comprehensive, systematic, and proactive approach to continuously improve
      everything that may, directly or indirectly, influence the quality of a
      preparation or service.

PMID- 24459787
TI  - Basics of compounding with tars.
AB  - Tar has been used throughout history for numerous purposes; from sealing the
      hulls of ships to sealing roofs of dwellings and even for medical purposes.
      Produced by destructive distillation, commonly used tars are prepared from coal
      and wood. Coal tar, juniper tar, and pine tar are used for various medical
      purposes as described in the article. Also presented are the various
      characteristics and uses of each tar, along with commercial products and numerous
      compounding formulas. Techniques used to compound with tars are also presented.

PMID- 24459788
TI  - In vitro evaluation of extemporaneously compounded immediate-release capsules
      with premixed excipients, based on the biopharmaceutics classification system
      (BCS) of the drugs.
AB  - Hard-capsule compounding plays an essential role in drug delivery for
      pharmaceutical application. Versatile and easy to use, capsules represent a
      popular dosage form for patients. Nevertheless, bioavailability of the drugs
      compounded in hard capsules is not always optimized and choosing the appropriate
      excipients is a key factor to improve the dissolution kinetics of active
      pharmaceutical ingredients. The Biopharmaceutical Classification System, which
      categorizes drugs regarding their solubility and permeability, is a unique tool
      which can be used to select the most compatible excipients for a particular drug
      when compounding immediate-release capsules. The aim of this study was to
      evaluate the efficiency of premixed excipient blends called CapsuBlend
      Excipients, based on the Biopharmaceutical Classification System concept, for
      drug dissolution rate and absorption enhancement. Drug assay and dissolution
      profiles were studied for three batches of metronidazole 250-mg, theophylline 100
      mg, and levocarnitine 250-mg capsules, each respectively representing a highly
      soluble, poorly soluble, and hygroscopic drug. Methods followed the
      specifications set forth in the United States Pharmacopeia. Assay results
      demonstrated that each batch of metronidazole 250 mg, theophylline 100 mg, and
      levocarnitine 250 mg contained not less than 90.0% of and not more than 110.0% of
      the labeled amount of drug, which is in accordance with the United States
      Pharmacopeia requirements. Moreover, dissolution profile results for the
      aforementioned capsules depicted dissolution values meeting the Pharmacopeial
      criteria of acceptance. These results reinforce the fact that the
      Biopharmaceutical Classification System concept represents a valuable guideline
      for formulation chemists or pharmacists to assist them for capsule compounding.
      To ensure a high level of efficiency of compounded capsules, premixed excipient
      blends, carefully developed by taking into consideration the solubility and
      permeability of a drug, represent a significant formulation advantage to improve
      the dissolution of active pharmaceutical ingredients.

PMID- 24459789
TI  - Pattern of extemporaneous prescriptions and preparations in a tertiary health
      institution: a five-year assessment.
AB  - Due to the increasing rate in the demand of extemporaneous formulations, it
      became necessary to assess the pattern of prescription and preparation in a
      developing institution. The purpose of this study was to assess the pattern of
      extemporaneous prescription and preparation in the University of Benin Teaching
      Hospital, Benin City, Nigeria. Records of prescription and preparation of
      extemporaneous formulations were assessed retrospectively between 2007 and 2011.
      Fifty-nine different types of drugs were prescribed with a frequency of 6,882
      times during the period. These were indicated for eight classes of systemic
      disease. Eighteen drugs were indicated for central nervous diseases, followed by
      16 drugs for cardiovascular diseases. Of the 18 drugs indicated for central
      nervous diseases, pyridoxine was the most common. Rifampicin for tuberculosis was
      the most frequently formulated, followed by spironolactone for cardiovascular
      disorders. Most preparations were labeled to be used for a maximum of two weeks.
      They were all liquid preparations packaged in amber-colored bottles. Distilled
      water was the most common vehicle utilized for trituration; while ascorbic acid
      syrup was commonly used to bulk the solution and as a sweetening agent. None of
      the patients reported with any form of pharmaceutical degradation or toxicity
      within two weeks of expected use. There were reports of spillages due to poor
      handling. Maximum volume prepared was 75 mL. The study suggests an adequate setup
      of a quality-control unit in the institution to meet the increasing demand for
      specific agents. This will enhance an effective healthcare delivery among
      patients.

PMID- 24459790
TI  - Compatibility of amiodarone hydrochloride with vasopressin during simulated Y
      site administration.
AB  - The objective of this study was to determine the compatibility of amiodarone
      hydrochloride with vasopressin during simulated Y-site administration. Amiodarone
      hydrochloride is compatible with vasopressin under simulated-use conditions when
      administered according to the Advanced Cardiac Life Support Guidelines. A
      simulated-use approach is a more appropriate way to evaluate compatibility of
      drug solutions and to assure safe and adequate drug delivery to the patient,
      particularly when the drug being evaluated is well-documented to have physical or
      chemical incompatibility concerns with various drugs. When amiodarone
      hydrochloride (50 mg/mL) was diluted to 6 mg/mL with 5% dextrose injection, then
      mixed with an equal volume of vasopressin (0.2 units/mL in normal saline) in a
      glass test tube, no visual incompatibility was observed for up to 24 hours. The
      purpose of our study was to assess compatibility of the two drugs under simulated
      use conditions and to measure the recovery of amiodarone by high-performance
      liquid chromatography after sequential administration of vasopressin and
      amiodarone hydrochloride according to the Advanced Cardiac Life Support
      Guidelines.

PMID- 24459791
TI  - GMPs vs GCPs: United States Pharmacopeia General Chapters.

PMID- 24459792
TI  - Modeling of blood lead levels in astronauts exposed to lead from microgravity
      accelerated bone loss.
AB  - INTRODUCTION: Most astronauts experiencing prolonged microgravity undergo
      accelerated bone loss at a whole-body rate of 0.5-1% per month, with some load
      bearing bones losing mass at normalized rates up to about 2.6% per month. The
      accompanying release of lead (Pb) stored in bones would increase the
      concentration of Pb in the blood (PbB), thereby complicating efforts to set
      acceptable Pb concentrations for spacecraft drinking water (PbW). METHODS: A
      physiologically based pharmacokinetic (PBPK) model was modified to permit
      modeling the effects on PbB of temporarily increased rates of bone loss and
      various PbW concentrations. RESULTS: The model predicts that, for the average
      American astronaut, the increase in PbB due to Pb released from bones would be
      more than offset by decreases in ingested or inhaled spacecraft environmental Pb,
      so that calculated PbB levels actually decrease in microgravity when PbW < about
      9 microg Pb x L(-1). Measured PbB in astronauts before and immediately after 6-mo
      stays on the International Space Station (ISS) support these results. Currently,
      PbW on the ISS averages 0.6 microg Pb x L(-1) and PbW on Earth at the Johnson
      Space Center averages about 5 microg Pb x L(-1). CONCLUSIONS: Most astronauts on
      long spaceflights will not be adversely affected by the release of lead from
      bones into the blood. A small percentage of astronauts (assuming there could be
      any who would have high concentrations of lead in their bones) could be at risk
      of experiencing elevated levels of PbB due to microgravity-accelerated release of
      Pb from their bones, depending on their individual rate of bone loss.

PMID- 24459793
TI  - Inert gas narcosis and the encoding and retrieval of long-term memory.
AB  - BACKGROUND: Prior research has indicated that inert gas narcosis (IGN) causes
      decrements in free recall memory performance and that these result from
      disruption of either encoding or self-guided search in the retrieval process. In
      a recent study we provided evidence, using a Levels of Processing approach, for
      the hypothesis that IGN affects the encoding of new information. The current
      study sought to replicate these results with an improved methodology. METHODS:
      The effect of ambient pressure (111.5-212.8 kPa/1-11 msw vs. 456-516.8 kPa/35-41
      msw) and level of processing (shallow vs. deep) on free recall memory performance
      was measured in 34 divers in the context of an underwater field experiment.
      RESULTS: Free recall was significantly worse at high ambient pressure compared to
      low ambient pressure in the deep processing condition (low pressure: M = 5.6; SD
      = 2.7; high pressure: M = 3.3; SD = 1.4), but not in the shallow processing
      condition (low pressure: M = 3.9; SD = 1.7; high pressure: M = 3.1; SD = 1.8),
      indicating IGN impaired memory ability in the deep processing condition. In the
      shallow water, deep processing improved recall over shallow processing but,
      significantly, this effect was eliminated in the deep water. DISCUSSION: In
      contrast to our earlier study this supported the hypothesis that IGN affects the
      self-guided search of information and not encoding. It is suggested that IGN may
      affect both encoding and self-guided search and further research is recommended.

PMID- 24459794
TI  - Neck injury criteria formulation and injury risk curves for the ejection
      environment: a pilot study.
AB  - BACKGROUND: Helmet mounted displays provide increased pilot capability, but can
      also increase the risk of injury during ejection. The National Highway
      Transportation Safety Administration's (NHTSA's) neck injury criteria (Nij)
      metric is evaluated for understanding the impact of helmet mass on the risk of
      injury and modified risk curves are developed which are compatible with the needs
      of the aviation community. METHODS: Existent human subject data collected under
      various accelerative and head loading conditions were applied to understand the
      sensitivity of the Nij construct to changes in acceleration and helmet mass, as
      well as its stability with respect to gender, body mass, neck circumference, and
      sitting height. A portion of this data was combined with data from an earlier
      postmortem human subject study to create pilot study modified risk curves. These
      curves were compared and contrasted with the NHTSA risk curves. RESULTS: A
      statistically significant difference in the peak mean Nij was observed when seat
      acceleration increased by 2 G, but not when helmet mass was varied from 1.6 kg to
      2 kg at a constant seat acceleration of 8 G. Although NHTSA risk curves predict a
      13% risk of AIS 2+ injury for the 8-G, 2-kg helmet condition mean Nij of 0.138,
      no AIS 2+ injuries were observed. Modified risk curves were produced which
      predict a 0.91% risk of AIS 2+ injury under these conditions. DISCUSSION: The Nij
      was shown to be sensitive to changes in acceleration and generally robust to
      anthropometric differences between individuals. Modified risk curves are proposed
      which improve risk prediction at lower Nij values.

PMID- 24459795
TI  - A 5-year review of atrial fibrillation in military aircrew.
AB  - INTRODUCTION: Atrial fibrillation (AF) is a common cause of disqualification from
      flying in both civilian and military aircrew. We reviewed 5 yr of atrial
      fibrillation management in the Royal Air Force (RAF) from both a clinical and
      occupational perspective. METHODS: Patients were identified from the RAF Medical
      Boards (RAFMB) electronic database using search terms "atrial," "fibrillation,"
      and "arrhythmia." Management was compared to current RAF and national clinical
      guidelines and current civilian and military aviation medicine policy. RESULTS:
      Over the 5-yr period assessed, 23 aircrew were identified with AF. Paroxysmal AF
      (PAF) was the most common diagnosis. Five aircrew remained fit to fly with no
      limitations, 12 fit to fly with restrictions, and 6 were graded permanently unfit
      for flying, with one of these being medically discharged. DISCUSSION: The
      incidence and demographics of aircrew identified with AF in this paper is
      comparable to previous studies. All aircrew in our study were treated in
      accordance with current RAF/national guidelines. Emerging treatments such as
      radiofrequency ablation and the new anticoagulants remain to be assessed for
      suitability in a military context. CONCLUSION: Management of AF in RAF aircrew
      requires a holistic approach, with an awareness of the arrhythmogenic aviation
      environment in which RAF aircrew operate. Most RAF aircrew with AF will retain a
      restricted flying status, but this should be considered on a case-by-case basis.

PMID- 24459796
TI  - Tactile cues for orienting pilots during hover over moving targets.
AB  - INTRODUCTION: Providing information via the tactile sensory system allows the
      pilot to increase awareness without further taxing the visual and auditory
      perceptual systems. In this study, tactile cues were presented to pilots for
      target orientation during a simulated helicopter extraction over a moving target.
      The efficacy of the cues provided by the tactile system was assessed under
      various conditions (rested vs. fatigued, clear vs. degraded visual environment).
      METHODS: This study employed a mixed-model 2(4) factorial design, including one
      between-subjects variable (training amount: minimal, additional) and three within
      subjects variables (state: rested, fatigued; visual environment: clear, degraded;
      tactile cue belt: active, inactive). Across 2 d under the 4 test conditions, 16
      UH-60 rated, healthy aviators completed 8 sessions of 10-min stabilized hovering
      maneuvers over a moving target. All flights were conducted in a UH-60 flight
      simulator. RESULTS: Subjects were able to stay closer to the target when the
      tactile cuing system was active (M = 31.14 ft, SE = 3.17 ft) vs. inactive (M =
      36.33 ft, SE = 2.84 ft). Likewise, subjects rated their situation awareness as
      greater when the tactile system was active vs. inactive. DISCUSSION: The results
      support the efficacy of the tactile system in providing directional cues for
      maintaining pilot performance during a hover maneuver over a moving target.

PMID- 24459797
TI  - Terrain stiffness and ankle biomechanics during simulated half-squat parachute
      landing.
AB  - BACKGROUND: A hard surface is potentially one of the risk factors for ankle
      injuries during parachute landing, but this has never been experimentally
      validated. This study was designed to evaluate the effects of terrain stiffness
      on ankle biomechanics during half-squat parachute landing (HSPL). METHODS: Eight
      male and eight female healthy participants landed on three surfaces with standard
      HSPL technique. The three surfaces were cushioned mats with different thicknesses
      (0 mm, 4 mm, and 8 mm). The effects of terrain hardness and gender and their
      interaction with ground reaction forces, ankle kinematics, and electromyograms of
      selected lower-extremity muscles were statistically analyzed with multivariate
      analysis of variance. RESULTS: The effects of terrain stiffness and the
      interaction between factors on all variables were not statistically significant.
      The effects of gender were not statistically significant on most variables. The
      peak angular velocity of the ankle dorsiflexion was significantly lower in men
      (mean 1345 degree x s(-1)) than in women (mean 1965 degree x s(-1)). A spongy
      surface even eliminated the differences between men compared to women in the
      activity of their tibialis anterior during simulated HSPL. DISCUSSION: Terrain
      stiffness, in the ranges tested, did not appear to influence ankle biomechanics
      among individuals performing HSPL. Additional studies are required to know
      whether this finding is applicable to realistic parachuting.

PMID- 24459798
TI  - Military aircrew and noise-induced hearing loss: prevention and management.
AB  - Modern-day high performance aircraft are more powerful, more efficient, and,
      unfortunately, frequently produce high noise levels, resulting in noise-induced
      hearing loss (NIHL) in military aircrew. Military pilots are required to perform
      many flight duties correctly in the midst of many challenges that may affect
      mission completion as well as aircraft and aircrew safety. NIHL can interfere
      with successful mission completion. NIHL may also require aircrew to be
      downgraded from flying duties, with the incumbent re-training costs for
      downgraded personnel and training costs for new/replacement aircrew. As it is not
      possible to control the source of the noise without compromising the efficiency
      of the engine and aircraft, protecting the aircrew from hazards of excessive
      noise and treating NIHL are of extreme importance. In this article we discuss
      various personal hearing protection devices and their efficacy, and
      pharmacological agents for prevention and management of NIHL.

PMID- 24459799
TI  - Retinal non-visual photoreception in space.
AB  - BACKGROUND: Circadian rhythm disruption occurs during spaceflight, leading to
      crew health and performance decrements. Spaceflight-related retinal changes,
      including oxidative stress and neuronal loss, have been previously reported in
      mice. METHODS: Animal tissue from experiments aboard shuttle missions STS-133
      (BALB/cJ mice, albino strain) and STS-135 (C57BL mice, pigmented strain), along
      with ground controls, was examined to determine survival of intrinsically
      photosensitive retinal ganglion cells (ipRGC) and melanopsin expression in
      retinas of mice exposed to the spaceflight environment. Real-time qPCR (RTqPCT)
      and microarray approaches were used to analyze Opn4 (melanopsin) gene expression,
      while immunohistologic studies were conducted to detect melanopsin localization
      in the retina. RESULTS: Opn4 expression was decreased in albino BALB/cJ mice
      exposed to spaceflight, as measured by RTqPCR, but not in C57BL mice samples as
      analyzed by microarray. Opn4 expression returned to control levels at 7 d
      postreturn in the BALB/cJ samples. Melanopsin positive RGCs were found in the
      expected proportion in all samples, except for the BALB/cJ samples at 1 d after
      flight, where virtually no immunoreactive cells were found. DISCUSSION:
      Spaceflight environmental factors may affect the nonvisual function of the
      retina, mediated by a reduction in melanopsin expression and ipRGC survival,
      contributing to circadian disruption.

PMID- 24459800
TI  - Flight schedules and occupational accidents among cabin crew: a longitudinal
      study.
AB  - BACKGROUND: Flight schedules of cabin crew involve early starts, long working
      hours, night flights, and the crossing of time zones, all of which might
      contribute to the risk of onboard occupational accidents. Because it is unclear
      if cumulative flight schedule exposure affects the incidence of occupational
      accidents, the objective of this study is to examine this association among cabin
      crewmembers. METHODS: Data from the 5-yr historic MORE cohort was used. The study
      population consisted of 6311 cabin crewmembers. For each employee, all flight
      schedules from 2005 to 2008 and registered occupational accidents in 2009 were
      collected. The association between the cumulative exposure to different types of
      flights and the occurrence of occupational accidents was determined using
      logistic regression analyses. RESULTS: In 2009, 289 cabin crewmembers reported at
      least 1 occupational accident. The adjusted logistic regression models showed
      that the number of short-haul flights during the period 2005-2008 was positively
      associated with the occurrence of occupational accidents in 2009. Less exposure
      to long-haul flights was also associated with reporting an occupational accident.
      DISCUSSION: The results of this study suggest that cumulative exposure to short
      haul flights is associated with an increased risk for occupational accidents
      among cabin crewmembers. This increased risk may be caused by the specific
      characteristics of short-haul flights. Future research should focus on possible
      underlying mechanisms, such as fatigue accumulation, and on the influence of
      adjustments to short-haul schedules. Airline companies can increase their focus
      on the short-haul operation in order to reduce onboard accidents.

PMID- 24459801
TI  - Fitness, blood, and urine measurements from the 2009 European astronaut selection
      medical examination.
AB  - INTRODUCTION: The European Space Agency conducted an astronaut selection campaign
      in 2008-09 which attracted over 8000 applicants. Of those, 45 made the final
      assessment stage: the medical examination (MEX). This retrospective,
      observational study reports exercise and fitness data, lipid profiles and other
      results of interest from the blood and urine samples of this niche subpopulation.
      METHODS: All the applicants that reached the MEX completed a Bruce protocol test
      and a standard blood draw (12 h of fasting, water intake was ad libitum) was
      collected together with a 24-h urine collection. All the results were compared to
      either a comparative population or reference range. RESULTS: The applicants had
      comparable fitness levels to the 90th percentile of their age group. The lipid
      profiles were observed to be within the 'optimal' or 'desirable' ranges.
      Bilirubin and creatinine clearance were measured at 1.2 (+/- 0.40) mg x dl(-1)
      and 131.0 (+/- 25.81) ml x min(-1), respectively, and both were shown to be
      significantly higher than their respective normative ranges, while urinary
      creatinine (0.65 (+/- 0.19) g x L(-1)) was significantly lower than the reference
      range. DISCUSSION: Overall, the results from the Bruce protocol and lipid profile
      show that the final round applicants were in good health and physically active.
      The most likely cause of the elevated bilirubin and creatinine levels was 'last
      minute' exercise conducted by the final round applicants before the MEX and the
      low levels of urinary creatinine may be attributed to drinking high quantities of
      water with an associated hypovolemia, diluting the urine.

PMID- 24459802
TI  - Differential diagnosis considerations of sickness after rapid pressure changes at
      altitude.
AB  - INTRODUCTION: Aviation has undergone significant advancement over time; despite
      our best practices, injuries can still occur. Occasionally aviators will suffer
      from injuries of barotrauma, decompression sickness, or arterial gas embolism.
      The history and physical examination are important when evaluating the injury and
      its subsequent treatment. This article will help readers identify key components
      of the history and physical examination in a patient to recognize decompression
      sickness and arterial gas embolism. CASE REPORT: This case report is of a Naval
      F/A-18C pilot who demonstrated acute and delayed neurologic symptoms when his
      cockpit underwent four rapid decompression cycles from 11,000 to 29,000 ft (3353
      to 8839 m) in a 20-s period. He was subsequently treated with hyperbaric oxygen
      via a standard U.S. Navy TreatmentTable 6 with complete neurological recovery as
      determined by his improved neurological abilities. DISCUSSION: Naval aviators are
      exposed to multiple stresses during flight. When injuries occur it is important
      to obtain a careful history and physical examination. A broad differential
      diagnosis, including decompression sickness, hypoxia, and arterial gas embolism,
      should be considered to ensure prompt and appropriate evaluation and treatment.
      In this case report, the pilot had acute neurological injuries concerning for
      arterial gas embolism or an hypoxic episode, as well as a delayed recurrence of
      symptoms consistent with decompression sickness.

PMID- 24459803
TI  - Recurrent idiopathic painless shoulder weakness in a Navy F/A-18 aviator.
AB  - Brachial plexopathies of various etiologies are commonly discussed in the
      literature; however, recurrent painless shoulder weakness is an uncommon event,
      especially in an otherwise healthy adult man. A designated Naval F/A-18 E/F
      aviator presented with acute right-sided, painless shoulder girdle weakness that
      initially presented 2 yr earlier in a similar fashion. Extensive medical workups
      during both episodes did not reveal any identifiable cause. This case report
      discusses the most common etiologies of shoulder weakness. Additionally, we
      discuss the aviator's most recent presentation and evaluation for acute shoulder
      weakness. Lastly, we propose a hypothesis as to the cause of the patient's
      symptoms based on a review of the literature.

PMID- 24459804
TI  - A hermetically sealed, fluid-filled surgical enclosure for microgravity.
AB  - INTRODUCTION: Expeditionary spaceflight is fraught with significant risks to
      human health, including trauma and other emergency medical events. To address
      several of the basic challenges of surgical care in reduced gravity, we are
      developing the Aqueous Immersion Surgical System (AISS), an optically clear
      enclosure pressurized by a fluid medium. The AISS is designed to prevent
      contamination of the spacecraft with blood and tissue debris, reduce
      intraoperative blood loss, and maintain visualization of the operative field.
      METHODS: An early prototype of the AISS was tested in reduced gravity during
      parabolic flight. A clear, aqueous field was created in a watertight chamber
      containing a mock vascular network. Hemorrhage was simulated by severing several
      of the analogue vessels. Experiments were performed to evaluate the benefits of
      surrounding a surgical cavity with fluid medium, as compared to an air
      environment, with respect to maintaining a clear view and achieving hemostasis.
      RESULTS: Qualitative evaluation of audio and video recorded during parabolic
      flight confirm AISS capacity to maintain visualization of the surgical field
      during a hemorrhage situation and staunch bleeding by raising interchamber
      pressure. DISCUSSION: Evaluation of the AISS in reduced gravity corroborates
      observations in the literature regarding the difficulty in maintaining
      visualization of the surgical field when performing procedures in an air
      environment. By immersing the surgical field in fluid we were able to apply
      suction directly to the hemorrhage and also achieve hemostasis.

PMID- 24459805
TI  - Interventional radiology: the future of surgery in microgravity.
AB  - Explorer Class missions face situations requiring innovative answers, including
      medical/surgical dilemmas. Interventional radiology (IR) could play a very
      important role as sonographically guided procedures make possible many minimally
      invasive surgical solutions. A review of IR was performed, including performing
      many IR procedures. Surgical equipment is limited in microgravity. General
      anesthesia, surgical skill, large mass/volume equipment, and
      postsurgical/postanesthesia care are among the reasons that open
      compartment/laparoscopic procedures are undesirable. Sonographically guided
      percutaneous procedures treat these issues with minimal sedation. Catheters are
      interchangeable and extremely lightweight and placement could be performed with
      0.5 lb (0.2268 kg) of material, nearly a 1000 fold decrease in mass from normal
      surgical devices. These carry a lower risk of complications comparable to
      surgery. These can further be researched using the KC-135 and remote "bases."
      Although further research is required, IR is ideally suited to handle many
      predicted medical problems that might arise during Explorer Class missions. The
      percutaneous treatment would allow symptoms to resolve during the mission, and be
      fully cured upon return to Earth.

PMID- 24459806
TI  - You're the flight surgeon: acute myocardial infarction.

PMID- 24459807
TI  - You're the flight surgeon: deep vein thrombosis.

PMID- 24459808
TI  - This month in aerospace medicine history.

PMID- 24459809
TI  - Adult mesenchymal stem cells and their potency in the cell-based therapy.
AB  - Recent advances in the field of regenerative medicines manifested the unique
      properties of stem cells including the ability of self-renewal and
      differentiation to make them available for their replacement in tissue injury.
      Mesenchymal stem cells (MSCs) are important tools in treating immune disorders
      and in tissue repair due to their multipotency, immunosuppressive properties, and
      production of cytokines or growth factors. MSC-mediated therapy is a fast-growing
      field that has proven safe and effective in the treatment of various degenerative
      diseases and tissue injuries. Generation of induced pluripotent stem (iPS) cells
      holds a great promise for regenerative medicine and other aspects of clinical
      applications. The mechanisms governing multipotency in MSCs are not well
      understood. This review mainly throws light on the biology of MSCs, including
      their efficiency in treating several diseases and also the progress of the use of
      iPSC-derived MSC widely in the clinic.

PMID- 24459810
TI  - Nodal, Nanog, DAZL and SMAD gene expression in human amniotic fluid stem cells.
AB  - The aim of this study was to investigate the expression of Nodal (NODAL Homolog
      (mouse), Nanog (Nanog Homeobox), DAZL (Deleted in Azoospermia Like) and SMAD
      (SMAD Family member) genes and their potential role in the regulation of self
      renewal in human amniotic fluid-derived stem cells. In this experimental study
      human amniotic fluid-derived stem cells were analyzed for messenger RNA
      expression of Nodal. Immunocytochemistry also was performed to determine Nanog
      and DAZL. SMAD genes expression analysis was performed using cDNA Microarray
      analysis. Nodal mRNA was positively expressed in all samples of amniotic fluid
      derived stem cells. Amniotic fluid-derived stem cells showed strong
      immunoreactivity for molecular markers of undifferentiated human embryonic stem
      cells including Nanog and DAZL. Among the 8 SMAD genes expressions analyzed
      SMAD1, SMAD2, SMAD3, SMAD4 and SMAD7 showed positive expression. In conclusion
      amniotic fluid-derived stem cells seem to express Nodal, Nanog and DAZL and it
      speculated that the regulation of self-renewal in AFSc could be similar as in
      human embryonic stem cells.

PMID- 24459811
TI  - Regenerative potential of dental pulp mesenchymal stem cells harvested from high
      caries patient's teeth.
AB  - Dental pulp are known to contains stem cells or dentinogenic progenitors that are
      responsible for dentin repair. Dental pulp Stem cells from Human Exfoliated
      Deciduous teeth (SHED) represent a population of postnatal stem cells capable of
      extensive proliferation and multipotential or multilineage differentiations. This
      potential for tissue regeneration has become the current basis for dental pulp
      stem cell banking. Here, we have attempted to develop a protocol for harvesting
      stem cells from patients with High Caries tooth, which are most often electively
      discarded. We have characterized the stem cells with mesenchymal stem cell
      markers and have compared their potential to grow in culture, doubling times, and
      differentiate into different lineages, with normal bone marrow mesenchymal stem
      cells (MSCs). We observed that the MSCs from dental pulp grew faster, with lower
      doubling time, and had equal efficiency in differentiating to various lineages,
      when subjected to standard directed differentiation protocols. This paper
      establishes that discarded High Carries Tooth can be a good source for
      regenerative medicine and also could be a potential source for MSCs and dental
      pulp MSC banking.

PMID- 24459812
TI  - Effect of bFGF on HLA-DR expression of human bone marrow-derived mesenchymal stem
      cells.
AB  - There has been a steady rise in the therapeutic applications of bone marrow
      mesenchymal stem cells (BM-MSCs) because of their unique properties of
      multilineage differentiation and immune modulation as well as the ease in
      isolation. However, up-regulation of surface HLA-DR levels when maintaining MSCs
      in culture under the influence of mitotic factors such as Basic fibroblast growth
      factor (bFGF) is an area of concern when considering them for the purpose of
      clinical applications. Thus, we investigated the association of bFGF supplemented
      to the culture media and the surface expression levels of HLA-DR in BM-MSCs in
      order to optimize the yield, while keeping HLA-DR levels under permissible
      levels. Human BM-MSCs were culture expanded in the absence of bFGF and in the
      presence of 1 ng/ml or 2 ng/ml bFGF. The HLA-DR profile of the cultures was
      analyzed at the end of each passage. On comparing the percent HLA-DR+ cell
      population at different concentrations as well as absence of bFGF, significant
      differences were not observed in the HLA-DR expression levels of the MSC cultures
      which had reached complete confluence. However, variations in HLA-DR expressions
      levels were seen which could be traced to the age of cells in culture with values
      drastically reduced to below 4% on maintaining MSCs typically two to three days
      beyond achieving full confluence. On the basis of the findings from this study,
      no significant correlation could be established on the effect of bFGF in
      modulating HLA-DR surface expression of BM-MSCs. Instead, the data are suggestive
      of the reasoning that the duration for which BM-MSCs are maintained in culture
      directly influences their phenotypic characteristics in terms of HLA-DR
      expression levels, with lowest levels achieved on their prolonged maintenance in
      culture.

PMID- 24459813
TI  - The role of regulatory T cells in IgE-mediated food allergy.
AB  - Immunoglobulin (Ig) E-mediated food allergy is a type 2 helper T cell (TH2)
      dependent disease whose prevalence is increasing in industrialized countries as a
      direct consequence of reduced tolerance to food antigens. The generation of
      regulatory T cells (Treg) is a key component of oral tolerance, and compelling
      experimental evidence has demonstrated that functional allergen-specific Treg
      cells play a major role in healthy immune responses to allergens and clinically
      successful allergen-specific immunotherapy. In the particular case of IgE
      mediated food allergy, further investigations are required to firmly demonstrate
      the role of Treg cells during desensitization, induction of tolerance, or both,
      and several studies have also suggested a key role for these cells in healthy
      responses to food allergens. Treg cells are able to suppress the sensitization
      and effector phases of allergic reactions via several mechanisms of action based
      on multiple soluble and surface-binding molecules. Our knowledge of the
      mechanisms governing the generation of food allergen-specific Treg cells in the
      gastrointestinal mucosa, including the specific dendritic cell subsets involved
      in such processes, has increased significantly over the last decade. The
      identification of alternative tissues where oral tolerance to food allergens
      might occur in vive is crucial, not only for a better understanding of the
      pathophysiology of food allergy, but also for the development of alternative
      therapeutic interventions. Recent findings demonstrate that oral tolerance can be
      induced in the tonsils through generation and maintenance of functional allergen
      specificTreg cells. Further investigation in this area could pave the way for
      novel treatments of food allergy and other immune tolerance-related diseases.

PMID- 24459814
TI  - Recurrence of anaphylaxis in a Spanish series.
AB  - BACKGROUND: Anaphylaxis is a potentially fatal condition, and many patients
      experience recurrence. OBJECTIVE: We report the incidence of first recurrence of
      anaphylaxis in our series and examine the risk factors associated with
      recurrence. METHODS: A validated questionnaire was sent to 1512 patients and
      completed by 887. The chosen definition of anaphylaxis was that of the National
      Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network
      Symposium. We evaluated the incidence of first recurrence of anaphylaxis overall
      and by subtype (eg, drugs and foods) and attempted to determine associated risk
      factors. RESULTS: The total incidence rate of the first recurrence of anaphylaxis
      (same subtype) was 3.2 episodes per 100 person-years (95%CI, 2.83-3.63).
      Incidence was lower in drug anaphylaxis (2.0 episodes per 100 person-years) than
      in latex and food anaphylaxis (8.6 and 5.6 episodes per 100 person-years,
      respectively). Cox and ordinal logistic regression models revealed that a first
      recurrence was less likely with drug anaphylaxis than with food anaphylaxis. The
      risk of experiencing 1 or more recurrences was higher for foods, exercise, and
      idiopathic causes than for the other subtypes. CONCLUSIONS: The incidence rate
      for a first recurrence of the same subtype of anaphylaxis was 2 to 6 times lower
      than that published by other authors. Recurrence of anaphylaxis is more common in
      subtypes with an increased prevalence of atopy (food, idiopathic, latex) than in
      other subtypes (drugs, Anisakis). Consequently, particular attention should be
      paid to prevention and care in this population.

PMID- 24459815
TI  - Expression of the basophil-specific antibodies 2D7 and BB1 in patients with
      cutaneous Mastocytosis.
AB  - BACKGROUND: 2D7 and BB1 are thought to be basophil-specific markers. In this
      study, we tested both antibodies in different skin and mast cell disorders with
      the aim of determining whether it was possible to differentiate between benign
      and aggressive presentations of mastocytosis. METHODS: Using the antibodies 2D7,
      BB1, and c-Kit, we performed an immunohistochemical study of skin biopsy
      specimens from patients with cutaneous mastocytosis (15 urticaria pigmentosa and
      telangiectatic macularis eruptive perstans) and liver or bone marrow biopsy
      specimens from patients with systemic mastocytosis. A basophil leukemia cell line
      was used as a reference. Peripheral blood basophils from healthy donors were used
      as controls. RESULTS: We observed intense expression of 2D7 and BB1 in all skin
      biopsy specimens from patients with cutaneous mastocytosis. Immunostaining of
      liver and bone marrow specimens from patients with systemic mastocytosis with 2D7
      and BB1 antibodies was negative. Specimens from patients with either type of
      mastocytosis showed similarly strong expression of c-Kit. The basophil cell line
      showed a 2D7 and a BB1 profile, with intense expression of c-Kit. Peripheral
      blood basophils exhibited notable immunostaining for 2D7, BB1, and c-Kit.
      CONCLUSIONS: 2D7 and BB1 are expressed in cutaneous mastocytosis, although this
      expression is lost when mast cell proliferation is systemic, thus reflecting
      either a different cellular differentiation stage or the presence of basophils in
      these skin diseases.

PMID- 24459816
TI  - Prospective, multicenter clinical trial to validate new products for skin tests
      in the diagnosis of allergy to penicillin.
AB  - BACKGROUND: Allergy to penicillin is the most commonly reported type of drug
      hypersensitivity. Diagnosis is currently confirmed using skin tests with
      benzylpenicillin reagents, ie, penicilloyl-polylysine (PPL) as the major
      determinant of benzylpenicillin and benzylpenicillin, benzylpenicilloate and
      benzylpenilloate as a minor determinant mixture (MDM). OBJECTIVE: To synthesize
      and assess the diagnostic capacity of 2 new benzylpenicillin reagents in patients
      with immediate hypersensitivity reactions to B-lactams: benzylpenicilloyl octa-L
      lysine (BP-OL) as the major determinant and benzylpenilloate (penilloate) as the
      minor determinant. METHODS: Prospective multicenter clinical trial performed in
      18 Spanish centers. Efficacy was assessed by detection of positive skin test
      results in an allergic population and negative skin test results in a
      nonallergic, drug-exposed population. Sensitivity, specificity, and negative and
      positive predictive values were determined. RESULTS: The study sample comprised
      94 allergic patients: 31 (35.23%) presented anaphylaxis, 4 (4.55%) anaphylactic
      shock, 51 (58.04%) urticaria, and 2 (2.27%) no specific condition. The culprit 8
      lactams were amoxicillin in 63 cases (71.60%), benzypencillin in 14 cases
      (15.89%), cephalosporins in 2 cases (2.27%), other drugs in 3 cases (3.42%), and
      unidentified agents in 6 cases (6.82%). The results of testing with BP-OL were
      positive in 46 cases (52.3%); the results of testing with penilloate were
      positive in 33 cases (37.5%). When both reagents were taken into consideration,
      sensitivity reached 61.36% and specificity 100%. Skin testing with penilloate was
      significantly more often negative when the interval between the reaction and the
      study was longer. CONCLUSIONS: The sensitivity of BP-OL and penilloate was 61%.
      Considering that amoxicillin was the culprit drug in 71% of reactions, these
      results indicate that most patients were allergic to the whole group of
      penicillins. These data support the use of benzylpenicillin determinants in the
      diagnosis of allergy to beta-lactams, even in predominantly amoxicillin-allergic
      populations.

PMID- 24459817
TI  - Comparison of 2 methods to correct for peripheral nitric oxide exchange in the
      lungs.
AB  - BACKGROUND AND OBJECTIVE: Two methods have been developed to account for the
      impact of airway nitric oxide (NO) production on alveolar NO (CANO)
      concentration. In the first (Condorelli method), CANo is corrected using
      bronchial NO flux (J'awNo) values, whereas in the second (Kerckx method),
      knowledge of the exhaled NO concentration at a flow of 50 ml/s (FENosO) is
      required. The aim of the present study was to determine the influence of each
      correction method on CANo values. METHODS: Ninety-one adults (27 asthmatics, 46
      patients with allergic rhinitis, and 18 healthy volunteers) were studied. FENO50
      was obtained according to a standardized method and exhaled NO was measured at
      multiple flows (100, 200, and 300 ml/s). CANO was adjusted for the trumpet shape
      of the airway tree and axial diffusion from central to peripheral airways using
      both the Condorelli and Kerckx methods. RESULTS: The mean (95% CI) CANO value
      obtained with the Condorelli method was 1.27 ppb (0.93-1.60), compared to 0.87
      ppb (0.55-1.19, P<.001) with the Kerckx method. Differences in CANO values
      obtained with each method were identified in individuals with high FENO50 values
      (n=55) and in those with normal FENO50 values (n=36), but were significantly
      greater in the first group (P=.01). CONCLUSIONS: Our findings suggest that CANO
      values obtained with the 2 methods reported to adjust for the trumpet shape of
      the airway tree and axial diffusion from central to peripheral airways are not
      equivalent and cannot be used interchangeably.

PMID- 24459818
TI  - Prediction of asthma by common risk factors: a follow-up study in Cuban
      schoolchildren.
AB  - OBJECTIVE: To determine which common risk factors, including environmental
      factors, are predictors for the development of asthma in Cuban schoolchildren.
      METHODS: A longitudinal study was conducted in 1042 schoolchildren without asthma
      at baseline in 2 Cuban municipalities. Asthma status in 2007, diagnosed using the
      International Study of Asthma and Allergies in Childhood questionnaire, was
      related to a set of common risk factors assessed in 2003/2004 in a multivariable
      logistic regression model. Multiple imputation was used for missing values. The
      final prediction model was obtained by backward selection (P<.15). The model's
      prognostic accuracy (R2) and discriminative ability (area under the receiver
      operating characteristic curve [AUC]) were assessed and internal validation by
      bootstrapping was performed. RESULTS: A family history of atopic diseases (odds
      ratio [OR], 2.19; 95% CI, 1.19-4.04), allergic sensitization (OR, 1.83; 95% CI,
      0.94-3.55), municipality (OR, 0.34; 95% CI, 0.15-0.74), and use of antibiotics in
      the child's first year of life (OR, 1.66; 95% CI, 0.89-3.11) were predictors for
      asthma development. The model had an R2 of 8.0% and a moderate discriminative
      ability (AUC, 0.69; 95% CI, 0.60-0.78). Internal validation hardly influenced the
      model's performance. CONCLUSIONS: Antibiotics use, genetic predisposition, and
      allergic sensitization were predictors of asthma in Cuban schoolchildren.
      Although known as common risk factors they could only partly predict asthma
      development. Poverty-related factors, such as low income and education, and
      parasitic infections, did not have an effect. Other or additional environmental
      predictors need to be identified, as these are potential targets for prevention
      and control of childhood asthma in affluent as well as nonaffluent countries.

PMID- 24459819
TI  - Changes in exhaled nitric oxide after inhalation challenge with occupational
      agents.
AB  - BACKGROUND AND OBJECTIVE: The use of fractional exhaled nitric oxide (FeNO)
      concentration has been proposed as a surrogate marker for monitoring airway
      response to specific inhalation challenge (SIC). We investigated the usefulness
      of FeNO measurements for monitoring airway response to SIC with occupational
      agents. Materialandmethods: Workers with suspected occupational asthma were
      recruited to undergo SIC with occupational agents and subsequently FeNO testing
      at baseline and 24 hours. RESULTS: Sixty-eight patients were evaluated, 45 of
      whom had a positive SIC. SIC-positive patients showed a significant increase in
      FeNO 24 hours postchallenge, with an increase ratio of 1.25 (95% CI, 1.05-1.48;
      P=.01); no increase was seen in patients with a negative SIC (P=.08). The
      predictive capacity of variations in FeNO showed that for each unit increase in
      FeNO, the probability of a positive SIC rose by 4%. A baseline FeNO value of 25
      ppb predicted a positive SIC with 60% sensitivity and 80% specificity. The
      increase in %FeNO cutoff point providing maximal sensitivity and specificity for
      predicting a positive SIC was 41% (sensitivity 50%, specificity 95%).
      CONCLUSIONS: We demonstrated that asthmatic reactions induced by occupational
      agents during SICs are associated with a consistent increase in FeNO. However,
      the predictive diagnostic capacity of FeNO measurements is low. While FeNO may
      aid in the interpretation of SIC in some cases, it cannot be used as a general
      surrogate marker to predict or to assess SICs with occupational agents.

PMID- 24459820
TI  - Interleukin 33 is induced by tumor necrosis factor alpha and interferon gamma in
      keratinocytes and contributes to allergic contact dermatitis.
AB  - BACKGROUND: Interleukin (IL) 33, a novel member of the IL-1 family, is produced
      mainly by epithelial cells and endothelial cells in response to various types of
      stress, including necrosis. The effects of IL-33 on the immune cells involved in
      allergic contact dermatitis have recently been revealed in vitro. However, in
      vivo, the induction mechanism and function of IL-33 are not fully understood.
      OBJECTIVES: Our objectives were to investigate induction of IL-33 in
      keratinocytes and to evaluate the functions of IL-33 and its inducers in a murine
      model of allergic contact dermatitis. MATERIAL AND METHODS: KERTr cells, a human
      keratinocyte cell line, were cultured with various cytokines, including tumor
      necrosis factor (TNF) alpha and interferon (IFN) gamma. IL-33 expression was
      detected using quantitative reverse transcriptase polymerase chain reaction,
      immunocytochemistry, and Western blotting. The functions of IL-33, TNF-a, and IFN
      y in allergic contact dermatitis were evaluated using a murine model. RESULTS:
      TNF-alpha and IFN-gamma induced expression of IL-33 mRNA and protein in KERTr
      cells. Blockade of IL-33 attenuated swelling in the ears of the experimental
      mice. Similar effects were noted for blockade of TNF-alpha and IFN-gamma in these
      mice. CONCLUSIONS: TNF-alpha and IFN-gamma induce expression of IL-33, and IL-33
      produced by keratinocytes contributes to allergic contact dermatitis. Blockade of
      IL-33, TNF-alpha, and IFN-gamma could represent novel and potent strategies to
      treat allergic contact dermatitis.

PMID- 24459821
TI  - Desensitizing oxaliplatin-induced fever: a case report.

PMID- 24459822
TI  - Occupational asthma due to polyvinyl chloride and methyl methacrylate in a
      plumber.

PMID- 24459823
TI  - Palpebral and periorbital edema in an immigrant woman.

PMID- 24459824
TI  - Knowledge of anaphylaxis among ibero-American physicians: results of the Ibero
      American Online Survey for Physicians on the management and treatment of
      anaphylaxis (IOSPTA) -Latin American society of Allergy, Asthma & Immunology
      (LASAAI).

PMID- 24459825
TI  - Pyruvate kinase and phosphopyruvate hydratase as novel IgE reactive proteins in
      prawn.

PMID- 24459826
TI  - Anaphylaxis caused by flaxseed.

PMID- 24459827
TI  - Characteristic of bacteriocines and their application.
AB  - Bacteriocines are small peptides with anti-bacterial properties. They are
      produced both by Gram-positive and Gram-negative bacteria. Until now, a few
      hundred bacteriocines were described. Classification of bacteriocines undergoes
      continuous alterations, as new developments regarding their structure, amino acid
      sequence and recognised mechanism of their action are available. Some of
      bacteriocins (lantibiotics) contain atypical amino acids, such as lantionine
      (Lan), methyllantionine (MeLan), dehydroalanine (Dha), dehydrobutyrine (Dhb), or
      D-alanine (D-Ala). The best recognized bacteriocines are produced by lactic acid
      bacteria, including nisine produced by strains of Lactococcus lactis. These
      bacteriocines have been recognized to be fully safe for humans. At present,
      nisine is used in food industry, as a preserving agent. Other lactic acid
      bacteria bacteriocines and probiotic preparations provide an alternative for
      antibiotics, and are used in food and in animal feed.

PMID- 24459828
TI  - The influence of toll-like receptor stimulation on expression of EBV lytic genes.
AB  - Epstein-Barr virus (EBV) establishes latency in the resting memory B-cell
      compartment. It has been recently suggested that maintenance of chronic infection
      is dependent on periodic reactivation. Although the stimuli for EBV reactivation
      in vivo during natural infections are largely unknown, there is evidence
      indicating that heterologous infections could trigger herpesviruses reactivation.
      The purpose of this work was to identify the influence of Toll-like receptors
      stimulation on EBV replication in EBV latently infected Burkitt lymphoma cells
      (P3HR-1, Raji and Namalwa). The cells were stimulated with Pam3CSK4 (synthetic
      triacylated lipoprotein), PolyI:C (synthetic analog of dsRNA), LPS
      (lipopolysaccharide from E.coli), measles virus (MeV) and PMA (phorbol myristate
      acetate). Non-stimulated cells (NS) served as control. EBV expression was
      investigated at mRNA level for three viral lytic genes: BZLF1 (immediate early,
      ZEBRA), BALF2 (early, EA) and BcLF1 (late, VCA). Additionally, the effect of
      stimulation on NF-kBp65 and inflammatory cytokines (IL-lb, IL-6, IL-8, IL-10, IL
      12p70, and TNF) was investigated. Stimulation of TLRs led to limited changes in
      EBV expression manifesting as increase of ZEBRA at mRNA level in cells treated
      with PolyI:C and Pam3CSK4. Stimulation with PolyI:C, Pam3CSK4 and LPS also lead
      to considerable increase of NF-kBp65, while increased levels of inflammatory
      cytokines were observed for IL-8, TNF and IL-6 in cells treated with PMA and MeV.
      In conclusion, the results of our experiments support the suggestion that TLRs
      stimulation with microbial ligands influences EBV virus replication.

PMID- 24459829
TI  - Effects of allicin on the formation of Pseudomonas aeruginosa biofinm and the
      production of quorum-sensing controlled virulence factors.
AB  - The Gram-negative Pseudomonas aeruginosa bacterial pathogen is reputed for its
      resistance to multiple antibiotics, and this property is strongly associated with
      the development of biofilms. Bacterial biofilms form by aggregation of
      microorganisms on a solid surface and secretion of an extracellular
      polysaccharide substances that acts as a physical protection barrier for the
      encased bacteria. In addition, the P aeruginosa quorum-sensing system contributes
      to antibiotic resistance by regulating the expression of several virulence
      factors, including exotoxin A, elastase, pyoverdin and rhamnolipid. The
      organosulfur compound allicin, derived from garlic, has been shown to inhibit
      both surface-adherence of bacteria and production of virulence factors. In this
      study, the effects of allicin on P aeruginosa biofilm formation and the
      production of quorum-sensing controlled virulence factors were investigated. The
      results demonstrated that allicin could inhibit early bacterial adhesion, reduce
      EPS secretion, and down-regulate virulence factors' production. Collectively,
      these findings suggest the potential of allicin as a therapeutic agent for
      controlling P aeruginosa biofilm.

PMID- 24459831
TI  - Genotypic diversity, antimicrobial resistance and screening of Vibrio cholerae
      molecular virulence markers in Vibrio alginolyticus strains recovered from a
      Tunisian Ruditapes decussatus hatchery.
AB  - In this study, a total of 54 Vibrio alginolyticus strains were analyzed. The
      isolates were recovered from different compartments of the Ruditapes decussatus
      hatchery in the National Institute of Marine Sciences and Technologies, Monastir,
      Tunisia. All isolates were biochemically identified (API 20E and API ZYM strips),
      characterized by amplification of the Hsp-40 gene polymerase chain reaction (PCR)
      and analyzed by enterobacterial repetitive intergenic consensus (ERIC)-based
      genotyping to evaluate genetic relationship between the isolated strains. We also
      looked for the presence of ten V cholera virulence genes (toxRS, toxR, toxT toxS,
      tcpP, tcpA, ace, vpi, zot and ctxA) in the genomes of Vibrio isolates. The
      antibiotics susceptibility, exoenzymes production and in vitro cytotoxic
      activitiy against HeLa cell line were also carried out for all tested bacteria.
      Most of V alginolyticus isolates showed significant antimicrobial resistance
      rates to at least ten antibacterial agents. For most isolates, the minimum
      inhibitory concentration (MIC) data showed that tetracydclin and streptomycin
      were the most effective antibiotics. Construction of the phylogenetic dendogram
      showed that studied isolates were in general genetically heterogeneous; however
      some Vibrio strains were present in different structures of the R. decussatus
      hatchery. The V cholerae virulence genes investigation showed a wild distribution
      of toxS (49/54), toxaR (45/54) and toxT (22/54) genes among V alginolyticus
      strains isolated from the R. decussatus rearing system. Cytotoxic effects of
      several Vibrio extracellular products (28154) were also observed on HeLa cells.

PMID- 24459830
TI  - Assessment of molecular diversity in chickpea (Cicer arietinum L.) rhizobia and
      structural analysis of 16S rDNA sequences from Mesorhizobium ciceri.
AB  - Molecular diversity studies of 19 rhizobia isolates from chickpea were conducted
      using simple sequence repeats (SSR) and 16S rDNA-RFLP markers. Phenotypic
      characterization with special reference to salinity and pH tolerance was
      performed. These isolates were identified as different strains of Mesorhizobium,
      Rhizobium, Bradyrhizobium, and Agrobacterium. Twenty SSR loci of Mesorhizobium
      ciceri, distributed across the other rhizobial genome, clearly differentiated 19
      rhizobial isolates. Analogous clustering supported the results of 16S rDNA
      sequence-based phylogeny. Analysis of the 16S rDNA sequences from M. ciceri
      strains revealed that nucleotide variables (signature sites) were located at 20
      different positions; most of them were present in the first 820 bp region from 5'
      terminal. Interestingly, 14 signature sites were located in two main regions, the
      variable region V1 (nt 527-584), and variable region V2 (nt 754-813). The
      secondary structure and minimal free energy were determined in these two regions.
      These results will be useful in characterizing the micro-evolutionary mechanisms
      of species formation and increase understanding of the symbiotic relationship.

PMID- 24459832
TI  - Salt stress tolerance of methylotrophic bacteria Methylophilus sp. and
      Methylobacterium sp. isolated from coal mine spoils.
AB  - Two methylotrophic strains of Bina coalmine spoil BNV7b and BRV25 were identified
      based on physiological traits and 16S rDNA sequence as Methylophilus and
      Methylobacterium species.' The strains exhibited similar carbon utilization but
      differed in N utilization and their response to the metabolic inhibitors.
      Methylophilus sp. was less tolerant to salt stress and it viability declined to
      one tenth within 4 h of incubation in 2M NaCI due to membrane damage and leakage
      of the intracellular electrolytes as evident from malondiaaldehyde (MDA) assay.
      In 200 mM NaCI, they exhibited increased superoxide dismutase (SOD), catalase
      (CAT) and ascorbate peroxidase (APX) activity while in 500 mM NaCI, enzyme
      activities declined in Methylophilus sp. and increased in Methylobacterium sp.
      Among exogenously applied osmoprotectants proline was most efficient; however,
      polyols (mannitol, sorbitol and glycerol) also supported growth under lethal NaCI
      concentration.

PMID- 24459833
TI  - Isolation of cultivable microorganisms from Polish notes and coins.
AB  - The potential role of currency in the spread of pathogenic microflora has been
      evaluated in many countries. In this study Polish paper notes and the coins in
      general circulation were assayed for the presence of cultivable bacteria and
      fungi. Bacterial isolates identification was based on cultural and biochemical
      characters and by comparison of the 16S rRNA gene sequence. Fungal isolates were
      recognized with biochemical and morphological criteria. Coagulase-negative
      staphylococci, (43.6% of the total bacterial count) including Staphylococcus
      saprophyticus, S. epidermidis, and S. hominis, and Enteroccus spp. (30.8% of the
      total bacterial count), i.e. E.faecalis, E.faecium and E. durans, were the most
      numerous bacterial contamination. Penicillium spp., and Aspergillus spp. were the
      most frequently detected moulds whereas Candida spp. was the most frequent yeast
      isolated from currency. A visible dependence between the banknote denomination,
      the physical condition of paper currency, and the number of bacteria and fungi
      was found. The overall count of bacteria isolated from currency was thousand-fold
      higher than that of fungal isolates. The total amount of bacteria and fungi
      recovered from the coins was approximately 2.7-fold lower than that isolated from
      the notes. In summary, the Polish currency notes were found to be contaminated
      mainly with commensal bacteria and fungi while the opportunistic pathogenic
      microorganisms Escherichia coli, Pseudomonas stutzeri and C. albicans were
      detected at a low frequency.

PMID- 24459834
TI  - Optimization of bioinsecticides overproduction by Bacillus thuringiensis subsp.
      kurstaki using linear regression.
AB  - A multiple linear regression analyses were performed to screen for the
      significant factors simultaneously influencing production of deltaendotoxin,
      proteolytic activities and spore formation by a Bacillus thuringiensis kurstaki
      strain. Investigated factors included: pH of the medium, available oxygen and
      inoculum size. It was observed that oxygen availability was the most influencing
      setting on both deltaendotoxins production and spores counts, followed by initial
      pH of the medium and inoculum size. On other hand, pH of medium was found to be
      the most significant parameter for proteolytic activity, followed by inoculum
      size and dissolved oxygen. Our results suggested that the first order with two
      factor interaction model seemed to be more satisfactory than simple first order
      model for optimization of delta-endotoxin overproduction. The coefficients of
      determination (R') indicated a better adequacy of the second order models to
      justify the obtained data. Based on results, relationships between delta
      endotoxins production, proteolytic activities and spores counts were established.
      Our results can help to balance delta-endotoxins production and its stability.

PMID- 24459835
TI  - Tigecycline susceptibility in multidrug resistant Acinetobacter isolates from
      Turkey.
AB  - The present study aimed to evaluate antimicrobial activity of tigecydcline
      against 84 multidrug resistant (MDR) Acinetobacter spp. strains by disc diffusion
      and E-test methods. The results of disc diffusion test were compared according to
      two different interpretation ways. In addition, E-test results and the disc
      diffusion results that interpreted by both the methods were checked for
      compatibility. According to the disc diffusion test, 3 strains (3.57%) were found
      resistant to tigecycline when considering breakpoints suggested by Food and Drug
      Administration (FDA). On the other hand, none of the strains was found resistant
      to the evaluation criteria recommended by Jones etal. (2007). Considering E-test
      results of tigecycline, MIC, and MICG, values of tigecycline for Acinetobacter
      spp. were 0.75 and 1 mg/l, respectively. Based on FDA defined breakpoints for
      Enterobacteriaceae, any resistant isolate was detected. In conclusion, although
      there are some differences in the results, tigecycline was found quite effective
      on Acinetobacter spp. isolates with reference to the both disc diffusion and the
      E-test methods.

PMID- 24459836
TI  - Distribution and virulence gene comparison of Aeromonas strains isolated from
      diseased fish and water environment.
AB  - A total of 71 Aeromonas strains were isolated in the south of Jiangsu Province
      China in order to analyze the difference ofAeromonas spp. distribution between
      diseased fish and water environment. The sequence of 16S rDNA and gyrB
      demonstrated that the 71 Aeromonas isolates could be divided into 4 species,
      including A. veronii (55), A. hydrophila (11), A. salmonicida (3) and A. media
      (2). A. veronii was the most common species isolated from fish and water
      environment. All Aeromonas isolates were screened for three putative virulence
      genes, aer, hly and alt. hly was the most common gene among three virulence
      genes.

PMID- 24459837
TI  - Identification of Scopulariopsis species by partial 28S rRNA gene sequence
      analysis.
AB  - The genus Scopulariopsis contains over 30 species of mitosporic moulds, which
      although usually saprophytic may also act as opportunistic pathogens in humans.
      They have mainly been associated with onychomycosis, and only sporadically
      reported as a cause of deep tissue infections or systemic disease. Identification
      of Scopulariopsis species still largely relies on phenotype-based methods. There
      is a need for a molecular diagnostic approach, that would allow to reliably
      discriminate between different Scopulariopsis species. The aim of this study was
      to apply sequence analysis of partial 28S rRNA gene for species identification of
      Scopulariopsis clinical isolates. Although the method employed did reveal some
      genetic polymorphism among Scopulariopsis isolates tested, it was not enough for
      species delineation. For this to be achieved, other genetic loci, within and
      beyond the rDNA operon, need to be investigated.

PMID- 24459838
TI  - Report on overcoming the poor quality of Apai pulsotypes with a short review on
      PFGE for listeria monocytogenes.
AB  - Since listeriosis, caused by Listeria monocytogenes, is one of the important
      concerns of public health in Europe related to foodborne zoonoses, an efficient
      protocol for isolate typing is necessary when performing epidemiological studies.
      Three standardized PFGE protocols available for L. monocytogenes were briefly
      reviewed. Since observing a poor-quality of ApaI pulsotypes in our laboratory,
      enzymes from three different manufacturers were compared. The obtained pulsotypes
      showed that restriction digestion with ApaI from New England BioLabs should be
      complemented with a subsequent overnight incubation of PFGE plugs in TE buffer
      for better performance.

PMID- 24459839
TI  - Endogenous or exogenous origin of vaginal candidiasis in Polish women?
AB  - Vaginal candidiasis is a common problem of clinical practice. Many studies have
      been conducted to explain its origin but only a few have included Polish women.
      The aim of the study was to determine the prevalence and similarity of oral, anal
      and vaginal Candida albicans strains isolated from Polish women with vaginal
      candidiasis. The study involved 20 from 37 recruited women. Swab samples were
      collected from their vagina, anus, and oral cavity at two-month intervals. All
      the women were treated with nystatin. Yeast were recovered and identified by the
      germ-tube test, API /Vitek system, typed by API ZYM and RAPD-PCR. Chi-square test
      was used to analyze the data. A total of 170 Candida albicans isolates were
      recovered from 180 samples collected 3 times from 3 sites of 20 women. Positive
      yeast vaginal cultures were found in all patients before administration of
      nystatin. Vaginal yeast recovery rate was decreased statistically significant in
      both follow-up visits (p= 0.001; p= 0.003). The same and different
      genotypes/biotypes were found concomitantly in a few body sites and/ or
      repeatedly at time interval from the same body site. The results support the
      concept of dynamic exchange of yeast within one woman and endogenous or exogenous
      origin of vaginal candidiasis.

PMID- 24459840
TI  - Beta-glucuronidase and Beta-glucosidase activity in stool specimens of children
      with inflammatory bowel disease.
AB  - The aim of the study was to analyze the differences in the activity of beta
      glucuronidase and beta-glucosidase in stool specimens of children with
      Inflammatory Bowel Diseases (IBD) and healthy subjects. The disease activity was
      determined according to the PCDAI scale (Crohn disease) and Truelove-Witts scale
      (Ulcerative colitis). Enzyme activity was determined by spectrophotometry. There
      was a correlation between the level of beta - glucosidase activity in stool and
      patient's age in the group of healthy controls, but not in the IBD group. beta
      glucosidase activity in IBD and healthy subjects stool specimens did not differ
      significantly. The activity of beta-glucuronidase in children with IBD was two
      times lower than in the healthy group and was correlated with age in children
      with IBD, but not in the group of healthy ones.

PMID- 24459841
TI  - Cellulase inhibits Burkholderia cepacia biofilms on diverse prosthetic materials.
AB  - Burkholderia cepacia is an opportunistic pathogen causing infections in patients
      with cystic fibrosis. Patients with implanted devices are prone to B. cepacia
      infections due to its ability to grow as biofilms. Knowing the importance of
      polysaccharides in a biofilm, enzymes that degrade them were targeted as a
      possible candidate for antibiofilm agents. In this study, the antibiofilm
      potential of cellulase against B. cepacia biofilms formed on various prosthetic
      materials was tested. Cellulase exhibited significant antibiofilm activity
      against B. cepacia without having much action on its growth, thus ruling out the
      chance of selection pressure and subsequent development resistance.

PMID- 24459842
TI  - Isolation and identification of microorganisms including lactic acid bacteria and
      their use in microbial deacidification of wines from domestic vineyards.
AB  - The aim of this study was to identify various bacteria isolated from grapes and
      their wines. Additionally we investigated the capacity of lactic acid bacteria
      for microbiological deacidification of wines produced in Poland. We have
      identified Oenococcus oeni, Lactobacillus acidophilus and Lactobacillus
      delbrueckii. During the microbial deacidification process, we observed decreases
      of total acidity and increases of volatile acidity, with statistically
      significant changes noted for O. oeni in Marechal Foch and Seyval Blanc, and for
      Lb. acidophilus in Frontenac. On the other hand, a statistically significant
      increase in pH was observed in Marechal Foch and Seyval Blanc following
      deacidification by O. oeni.

PMID- 24459843
TI  - [Determination of mRNA-transcripts and heat shock proteins HSP70 and HSP90 in
      retina of the adult Spanish Ribbed Newt Pleurodeles waltl].
AB  - Expression of genes and heat shock proteins in normal intact retina of the
      Spanish Ribbed Newt Pleurodeles waltl was studied using polymerase chain
      reaction, Western blot hybridization, and immunohistochemistry. It was shown that
      the proteins HSP70 and HSP90, as well as their encoding transcripts of relevant
      genes, are constitutively expressed in eye tissues. These proteins were
      distributed differentially, and they were characterized by expression of
      different levels in the retina: HSP70 dominated in the external retina, while
      HSP90 dominated in the internal one, in particular, in Muller glial cells and the
      optic nerve. Transcripts and heat shock proteins HSP70 and HSP90 were also found
      in the retinal pigment epithelium and eye growth zone.

PMID- 24459844
TI  - [Nitrogen oxide is involved in the regulation of the Fe-S cluster assembly in
      proteins and the formation of biofilms by Escherichia coli cells].
AB  - The functions of nitrogen oxide (NO) in the regulation of the reversible
      processes of Fe-S cluster assembly in proteins and the formation of Escherichia
      coli biofilms have been investigated. S-nitrosoglutathione (GSNO) and crystalline
      nitrosyl complexes of iron with sulfur-containing aliphatic ligands cisaconite
      (CisA) and penaconite have been used as NO donors for the first time. Wild-type
      E. coli cells of the strain MC4100, mutants deltaiscA and deltasufA, and the
      double paralog mutant deltaiscA/sufA with deletions in the alternative pathways
      of Fe2+ supply for cluster assembly (all derived from the above-named strain)
      were used in this study. Plankton growth of bacterial cultures, the mass of
      mature biofilms, and the expression of the SoxRS[2Fe-2S] regulon have been
      investigated and shown to depend on strain genotype, the process of Fe-S cluster
      assembly in iron-sulfur proteins, NO donor structure, and the presence of Fe2+
      chelator ferene in the incubation medium. The antibiotic ciprofloxacine (CF) was
      used as an inhibitor of E. coli biofilm formation in the positive control. NO
      donors regulating Fe-S cluster assembly in E. coli have been shown to control
      plankton growth of the cultures and the process of mature biofilm formation;
      toxic doses of NO caused a dramatic (3- to 4-fold) stimulation of cell entry into
      biofilms as a response to nitrosative stress; NO donors CisA and GSNO in
      physiological concentrations suppressed the formation of mature biofilms, and the
      activity of these compounds was comparable to that of CE Regulation of both Fe-S
      cluster assembly in iron-sulfur proteins and biofilm formation by NO is
      indicative of the connection between these processes in E. coli.

PMID- 24459845
TI  - [Bacterial complexes of the fruiting bodies and hyphosphere of certain
      basidiomycetes].
AB  - The surface and internal tissues of the fruiting bodies of basidiomycetes were
      shown to be specific bacterial habitats characterized by varying diversity and
      structure of bacterial complexes. On the surface of fruiting bodies, gram
      negative bacteria of the genera Pseudomonas, Xanthomonas, and Myxococcus
      prevailed, while in the internal tissues gram-positive bacteria of the genera
      Streptomyces, Bacillus, Arthrobacter, and Micrococcus were identified in
      addition. Bacterial complexes from the surface and inner tissues of the fruiting
      bodies of the studied basidiomycetes showed significant similarity to each other
      and differed from those from the hyphosphere and the reference soil. On the
      surface and in the internal tissues of the fruiting bodies, representatives of
      the genus Myxococcus were identified for the first time, which could indicate
      initial decay of the fruiting body.

PMID- 24459846
TI  - [Macrokinetic basis for the model of microbial growth in a limited volume under
      constant conditions with a single leading substrate].
AB  - Within the framework of the macrokinetic approach and continuum and
      chemical/biochemical gross reaction conceptions, an equation describing the
      complete dynamics of microbial growth and decline as function of a variable
      concentration of the leading substrate was deduced. This equation allows us to
      distinguish quantitatively and qualitatively the stages of microbial growth and
      the intervals of microbial tolerance to the initial concentration of the leading
      substrate. Adequacy of the model was confirmed by comparison with experimental
      dynamics of aerobic microorganisms in the samples of groundwater collected from a
      region polluted with uranium.

PMID- 24459847
TI  - [Interaction of the uterus and developing eggs in cyclophyllidean cestodes with
      different fecundity].
AB  - The interaction of morphological changes of the uterus and fecundity of the
      strobilus of cestodes has been investigated. It is shown that cestodes with
      maximal fecundity have different and highly effective ways of supplying eggs with
      nutrients. It is noted that differences in fecundity of cestodes depend not only
      on their strategy of reproduction, ecology, and complexity of life cycles but
      also on the complexity of interactions between the uterus and the developing
      eggs.

PMID- 24459848
TI  - [Carbohydrate metabolism parameters in the thick-billed murre (Uria lomvia)
      infested with Alcataenia armillaris (Cestoda: Dilepididae)].
AB  - Some aspects of carbohydrate metabolism in noninfested thick-billed murres (Uria
      lomvia) and those infested with the tapeworm Alcataenia armillaris (Cestoda:
      Dilepididae) are reported. The findings demonstrate that the intestinal invasion
      by A. armillaris causes a drop in the activity of digestive enzymes (glycosidases
      and sacharase) and decreases blood glucose levels and glycogen content in the
      liver. The main reasons underlying changes in avian carbohydrate metabolism in
      cestode invasion are suggested.

PMID- 24459849
TI  - [Calmodulin inhibitors suppress a calcium signal from serotonin receptors in
      smooth muscle cells and remove the vasoconstrictive response upon intravenous
      introduction of serotonin].
AB  - Comparative study of the effect of calmodulin inhibitors (trifluoperazine, W-12,
      and W-13) and the TRPVI channel blocker (capsazepine) on receptor-dependent
      calcium exchange in smooth muscle cells of the rat aorta and on the contractility
      of the isolated aorta was conducted. It was determined that trifluoperazine
      almost completely removes an increase in the concentration of calcium ions in the
      cytoplasm of smooth muscle cells (isolated from the rat aorta) and smooth muscle
      cells of the A7r5 line in response to serotonin and does not influence the cell
      response to vasopressin and angiotensin II. W-12 and W-13 also do not reduce
      calcium ion concentration increase (induced by vasopressin and angiotensin II)
      but reduces by two times its rise in response to serotonin. It was found that the
      efficiency of calcium exchange suppression by calmodulin inhibitors correlates
      with the intensity at which they inhibit the contractile response of the aorta on
      the effect of serotonin. It was detected that the inhibiting effect of calmodulin
      blockers on calcium exchange in smooth muscle cells and the contractility of the
      rat isolated aorta during the activation of serotonin vasoconstrictive receptors
      are realized by a TRPV1-independent mechanism. It was demonstrated in experiments
      in vivo that trifluoperazine does not influence hypotensive reaction in rats
      (normally observed in response to intravenous serotonin introduction), but
      removes the hypertensive effect of this neurotransmitter in rats after chronic
      introduction of dexamethasone. The results obtained confirm the hypothesis (that
      we previously stated) about the direct involvement of calmodulin in signal
      transmission from vasoconstrictive serotonin receptors.

PMID- 24459850
TI  - [Development of the noradrenergic system of the rat brain after prenatal exposure
      to corticosterone].
AB  - The influence of corticosterone during the period of tyrosine hydroxylase gene
      expression (16th-18th days of rat embryogenesis), which is sensitive to hormonal
      induction, on the ontogenesis of presynaptic markers of the noradrenergic system
      has been studied. It has been found that hormone-induced changes in the level of
      noradrenaline and dopamine in the brain cortex and brainstem had a transitive
      character and were eliminated in adulthood. At the same time, the hormone
      increased the activity oftyrosine hydroxylase in the cortex of 7- to 16-day-old
      rat pups and in the cortex and brainstem of adult animals. It has been shown that
      the level of glucocorticoids is an important factor in development of the
      noradrenergic system of the brain, able during critical periods of ontogenesis to
      cause sustained changes of its functioning in subsequent periods of life.

PMID- 24459851
TI  - [The modern concept of the regulatory role of peptides of the glyproline family
      in the correction of hemostasis system function during development of diabetes
      mellitus].
AB  - The experimental data on the therapeutic and prophylactic antidiabetogenic effect
      of di-, tri-, and tetrapeptides of the glyproline family with the additional
      inclusion of arginine or leucine at different positions are presented. The
      results are obtained using two animal models: with insulin-dependent diabetes
      mellitus (type 1), and persistent hyperglycemia similar to development of non
      insulin-dependent diabetes mellitus (type 2) in humans. It is shown that repeated
      intranasal administration of Pro-Gly, Pro-Gly-Pro, Pro-Gly-Pro-Arg, Pro-Gly-Arg,
      Arg-Pro-Gly, Arg-Pro-Gly-Pro, Gly-Pro-Arg, Pro-Arg-Gly, Pro-Gly-Pro-Leu, Leu-Pro
      Gly-Pro peptides to rats with hyperglycemia of different etiology led to the
      combined normoglycemic and anticoagulant effects in the blood plasma. The concept
      of the regulatory role of short proline-containing peptides, involving the
      universality of their action in the organism and directed towards the regulation
      of both hemostasis and insular systems in a variety of their physiological and
      clinical manifestations, was formulated.

PMID- 24459852
TI  - [Simulation of the competition for light in forest stands of the same age].
AB  - A model simulating the growth and interaction of trees during their competition
      for light has been proposed and verified. Qualitative analys of the model
      behavior at various values of parameters determining the tree growth rate has
      been performed. The model verification shows a sufficiently high accuracy of the
      model approximation of empirical tree growth data. To study interspecific
      interactions in forest communities, some computing experiments on the development
      of mixed forest stands, represented by the main forest-forming wood species of
      the Far East, have been carried out.

PMID- 24459853
TI  - [Response of forest communities of xylotrophic fungi to agrotechnical pollution:
      multimodel based inference].
AB  - Communities of xylotrophic basidial fungi of the South taiga subzone of the
      Middle Urals that are exposed to industrial air pollutants have been studied. We
      quantitatively assessed the dependence of basic cenotic parameters of
      xylomycocomplexes on the distance from the source of technogenic pollution and
      the peculiarities of forest substrates. It was noted that the species abundance
      and generative and competitive activity of basidial fungi significantly decrease
      upon approaching the source of air pollutants, and defects in the forest stand
      moderately increase. A higher activity of the phytopathogenic complex was shown
      in polluted regions as compared to a control background zone. The data were
      analyzed using generalized linear model theory. Akaike's criterion was used for
      the selection of optimal models.

PMID- 24459854
TI  - [Some physiological and biochemical indicators of underyearling Laxman's shrews
      (Sorex cecutiens Laxmann) and even-toothed shrews (Sorex isodon Turov) under
      conditions of different population densities].
AB  - Based on the results of a study conducted in 2006-2010 in the Buyunda River basin
      (a feeder of the Kolyma River), the influence of the population density of common
      shrews (Sorex) on some of the physiological and biochemical parameters (glycogen
      and lipids in the liver, the relative weight of the spleen, the white and brown
      adipose tissue cellularity of bone and brain tissue) was investigated. The
      content of energy reserve substances was correlated with the number of animals
      (fat deposits had a negative correlation; the glycogen content in the liver had a
      direct correlation). For the rest of the physiological-biochemical parameters, no
      significant correlation with the population density was detected, although for
      the content of brown fat and cellularity of bone marrow tissue in Sorex isodon,
      as well as the relative weight of the spleen in both species of shrews, a trend
      was observed. We suggest that the identified physiological changes indicate
      irregular feeding of animals in years with higher population densities.

PMID- 24459855
TI  - [Biological activity of soils in the settlements of southern (Microtus
      rossiaemeridionalis) and bank (Clethrionomys glareolus) voles].
AB  - The effect of southern (Microtus rossiaemeridionalis) and bank (Clethrionomys
      glareolus) voles on the biological activity of soddy-podzolic soil and culturozem
      has been studied. To estimate this effect, the activity of nitrogen and carbon
      transformation in the soil taken from the paths and different chambers of the
      holes of these rodents, as well as from the control plots where there were no
      voles, has been determined. The contents of organic carbon and nitrogen in the
      soil have been found. The parameters of functional diversity of the microbial
      community of soil have been studied. It has been noted that the effect of voles
      on the biological activity of the above soils manifested itself in increased
      intensity of aerobic and anaerobic destruction of organic matter and changes in
      the parameters of functional diversity of the microbial community of soils.

PMID- 24459856
TI  - [Photoperiodic conditions during molting of the Indian pied wagtail (Motacilla
      alba dukhunensis) and location of its winter habitats].
AB  - The results of studying molting before the start of the mating season in Indian
      pied wagtail yearlings taken from the nests in the Lower Ob' region and in the
      mid-Urals and kept in captivity for a year are studied. Reliable differences in
      the completeness of molting in northern birds as compared with it in mid-Ural
      birds are revealed, as are requirements for the wintering photoperiod. We assume
      the existence of a latitudinal differentiation during this period: 20 degrees-30
      degrees N for mid-Ural birds and 10 degrees-20 degrees N for northern wagtails.

PMID- 24459857
TI  - [Mixotrophy in microorganisms: ecological and cytophysiological aspects].
AB  - Mixotrophy is the ability to combine autotrophic and heterotrophic modes of
      nutrition. It is widely spread in various microorganisms, particularly in such
      important plankton groups as dinoflagellates and cyanobacteria. Mixotrophy has a
      significant impact on our comprehension of the matter and energy flows in marine
      ecosystems, and therefore, it is an object of much attention for several recent
      decades. Nevertheless, the precise data on the balance of auto- and heterotrophy
      during the mixotrophic growth have been absent so far, which is due, first of
      all, to insufficient understanding of physiological and molecular ground of this
      phenomenon. In this review we discuss some ecological and cytophysiological
      aspects of investigation of mixotrophy in microorganisms as well as possible
      reasons for relatively slow progress in this area.

PMID- 24459858
TI  - [Qualitative composition of carotenoids, catalase and superoxide dismutase
      activities in tissues of bivalve mollusc Anadara inaequivalvis (Bruguiere,
      1789)].
AB  - By using high-performance liquid chromatography, UV-VIS-spectra and mass spectra
      (FAB MS) in tissues of bivalve mollusc Anadara inaequivalvis (Bruguiere, 1789)
      there are identified seven kinds of carotenoids: trans- and cis-pectenolon,
      alloxanthin, pectenol A, beta-carotene, zeaxanthin, and diatoxanthin. Their
      quantitative ratio in hepatopancreas, gills, and foot of the animals was
      determined. There was revealed negative correlation (R2 about 0.9) between
      content of several carotenoids (trans- and cis-pectenolon, zeaxanthin,
      alloxanthin, and diatoxanthin) in tissues and activities of antioxidant enzymes
      (catalase and superoxide dismutase). The presence of competitive relations
      between these molecular systems is assumed and their underlying causes are
      discussed.

PMID- 24459859
TI  - [Photoreceptors and visual pigments in three species of newts].
AB  - Photoreceptor complement and retinal visual pigments in three newt (Caudata,
      Salamandridae, Pleurodelinae) species (Pleurodeles waltl, Lissotriton (Triturus)
      vulgaris and Cynops orientalis) were studied by light mucroscopy and
      microspectrophotometry. Retinas of all three species contain "red"
      (rhodopsin/porphyropsin) rods, large and small single cones, and double cones.
      Large single cones and both components of double cones contain red-sensitive
      (presumably LWS) visual pigment whose absorbance spectrum peaks between 593 and
      611 nm. Small single cones are either blue- (SWS2, maximum absorbance between 470
      and 489 nm) or UV-sensitive (SWS1, maximum absorbance between 340 and 359 nm).
      Chromophore composition of visual pigments (A1 vs. A2) was assessed both from
      template fitting of absorption spectra and by the method of selective bleaching.
      All pigments contained a mixture of A1 (11-cis retinal) and A2 (11-cis-3,4
      dehydroretinal) chromophore in the proportion depending on the species and cell
      type. In all cases, A2 was dominant. However, in C. orientalis rods the fraction
      of A1 could reach 45%, while in P. waltl and L. vulgaris cones it did not exceed
      5%. Remarkably, the absorbance of the newt blue-sensitive visual pigment was
      shifted by up to 45 nm toward the longer wavelength, as compared with all other
      amphibian SWS2-pigments. We found no "green" rods typical of retinas of Anura and
      some Caudata (ambystomas) in the three newt species studied.

PMID- 24459860
TI  - [Changes in lipid spectrum in rats with chronic heart failure of different
      severity on the background of angiotensin-converting enzyme inhibitors and beta
      adrenoblockers].
AB  - The character of lipid spectrum changes in rats with experimental heart failure
      of non-ischemic genesis depended on its severity. In mild heart failure there was
      found an increase in the low density lipoprotein levels, whereas in the severe
      one--a decrease of total cholesterol levels at the expense of the low density
      lipoproteins. The ACE inhibitors produced no significant changes in the lipid
      spectrum. The effect of beta-adrenoblockers was determined by their selectivity
      for beta1-adrenoreceptors. The most selective drugs were distinguished by the
      metabolically neutral activity. On the contrary, nonselective beta-adrenoblockers
      increased the degree of plasma atherogeneity.

PMID- 24459861
TI  - [Features of lysozyme content in cods (order Gadiformes) and flatfish (order
      Pleuronectiformes)].
AB  - The content of lysozyme as an indicator of nonspecific immunity in kidney, liver,
      spleen, and blood serum in 8 fish species of the order Gadiformes and the order
      Pleuronectiformes was analyzed. The Gadiformes are characterized by a very low
      level of enzyme or the absence of its activity in individual organs and serum,
      regardless of the fish habitat location. The Pleuronectiformes demonstrated
      diversity in content and distribution of lysozyme in the body of various fish
      species. Two plaice species with the unique distribution inhabiting the Sea of
      Okhotsk were found. This feature is due, first, to the highest lysozyme content
      in serum of the previously studied fish; second, to the 2-3-fold excess of the
      enzyme content in serum as compared with the studied immunocompetent organs. The
      obtained results confirm the opinion about the existence of various related
      groups among fishes which essentially differ in the lysozyme role in nonspecific
      immunity.

PMID- 24459862
TI  - [Action of La3+ on the systems providing contractility of vertebrate myocardium].
AB  - The inotropic action of La3+ on frog myocardium was studied with taking into
      account of its effect on mitochondria of cardiomyocytes (CM). It has been
      established that in the range of studied concentrations (0.2-6 mM), La3+
      decreases dose-dependently the strength of cardiac contractions (by 3.3-92.2 %).
      In parallel experiments on isolated rat heart mitochondria (RHM), La3+ at a
      concentration of 25 microM has been shown to cause swelling of non-energized and
      energized mitochondria in isotonic medium with 125 mM NH4NO3 and in hypotonic
      medium with 25 mM CH3COOK. The study of oxidative processes in mitochondria with
      aid of polarographic method of measurement of oxygen concentration has shown that
      La3+ at concentrations of 50 and 100 microM increases the oxygen consumption rate
      by mitochondria in the state 2. However, La3+ does not decrease the respiration
      rate of isolated mitochondria in the state 3, as this takes place in the case of
      use of Cd2+ or at the Ca(2+)-overloading of mitochondria. The rate of endogenous
      respiration of isolated mitochondria in the medium with La3+ was higher than in
      control, which implies its effect on ion permeability of the inner membrane. The
      data obtained in this work indicate that the La(3+)-produced decrease of the
      contractility of cardiac muscle is not only due to the direct blocking effect on
      the potential-controlled Ca2+ channels, but is also mediated by its unspecific
      action on the CM mitochondria. This action is manifested in acceleration of the
      energy-dependent K+ transport in matrix and in an increase of ion permeability of
      the inner mitochondrial membrane (IMM).

PMID- 24459864
TI  - [Acoustic components of agonistic behavior of house mouse (Mus musculus) males].

PMID- 24459863
TI  - [Dynamics of morphophysiological characteristics in female water voles (Arvicola
      amphibius L.) during pregnancy].
AB  - Pregnancy and lactation need increased energy consumption and are accompanied by
      morphological and physiological changes of various maternal organs and systems.
      In water voles, connection of female interior characteristics has been poorly
      studied. Under standard vivarium conditions, we evaluated morphophysiological
      parameters of non-reproducing females and of females at the early (1-7 days),
      intermediate (8-14 days), and late (15-21 days) stages of pregnancy. There were
      established effect of the reproductive state on mass of abdominal and brown fat,
      liver, adrenals, spleen and an increment of body mass (without uterus with
      embryos). In pregnant females, as compared with the non-pregnant ones, the blood
      thyroxin level was significantly lower (16.2 +/- 0.8 and 21.7 +/- 1.4 pmpl/l) and
      the blood testosterone level was higher (1.29 +/- 0.19 and 0.83 +/- 0.09 nmol/l).
      The blood glucose content fell in the end of pregnancy. Dynamics of
      morphophysiological parameters at the period of pregnancy reflects the
      compensatory body reactions providing preservation of embryos and preparation to
      breeding of offspring.

PMID- 24459865
TI  - [Lateralization of behavioral reactions and otolith asymmetry].
AB  - Lateralized behavior is widely spread among vertebrate animals and is determined
      first of ally by structural-functional brain asymmetry as well as by the presence
      of somatic and visceral asymmetry. Some kinds of asymmetric reactions are
      suggested to be due to the presence of asymmetry at the level of sense organs, in
      particular, of otolith organs. This review presents data on value and character
      of otolith asymmetry (OA) in animals of various species and classes, on action
      upon it of weightlessness and hypergravity; the problem of effect of OA on
      vestibular and auditory functions is considered. In symmetric vertebrates, OA has
      been shown to be of fluctuation character and its chi coefficient varies in
      diapason from -0.2 to 0.2; in the overwhelmed majority of individuals, /chi/ <
      0.06. The low OA level allows the paired otolith organs to work coordinately;
      this it why OA is at the equally low level regardless of the individual's
      taxonomic and ecologic position, its size, age, and otolith growth rate.
      Individuals with abnormally high OA level can experience difficulties in analysis
      of auditory and vestibular stimuli, therefore in nature the majority of such
      individuals are eliminated in the process of natural selection. Unlike
      symmetrical vertebrates, labyrinths of many Pleuronectiformes have pronounced OA-
      otoliths of the lower labyrinth, on a average, are significantly heavier than
      those of the upper labyrinth. Their organs are the only example when OA with
      directed character seem to play an essential role in lateralized behavior and are
      suggested to be used in the spatial localization of the sound source. The short
      time action of weightlessness and relatively weak hypergravity (< or = 2g) do not
      affect OA. However, it cannot be ruled out that the long-term stay under
      conditions of weightlessness and hypergravity > or = 3g, as well as some diseases
      and shifts connected with processes of aging can enhance OA and cause several
      functional disturbances.

PMID- 24459866
TI  - [Oxygen-binding capacities of hemoglobin and nitric oxide].
AB  - The analysis of the literature and our own results indicates that a nitric oxide
      carries out a role the allosteric effector of hemoglobin, changing its affinity
      to oxygen and defining a condition of oxygen transport blood function. It is
      important point for modification of functional properties of hemoglobin and its
      participation in the flow of oxygen in tissues, which plays an important role in
      development of disadaption reactions at stress and decreased bioactivity of the
      nitric oxide at the endothelial dysfunction. These findings give possiblity to
      creat the new ways to correct hypoxical conditions through influence on oxygen
      binding properties of the blood and activity of L-arginin-NO system.

PMID- 24459867
TI  - [Problem of end-effector of ischemic postconditioning of the heart].
AB  - Analysis of literature source indicates that main pretenders to the role of end
      effectors of ischemic postconditioning of the heart are: 1) Ca(2+)-dependent K+
      channel of BK-type (big conductance K+ channel), 2) mitoK(ATP) channel
      (mitochondrial ATP-sensitive K(+)-channel), 3) MPT pore (mitochondrial
      permeability transition pore). At the same time, some investigators consider that
      mitoK(ATP) channel is only an intermediate link in the series of signaling events
      ensured an increase in cardiac tolerance to impact of ischemia-reperfusion. The
      most likely end-effector of the three structures is MPT pore. Alternatively, it
      is possible, that unique molecular complex appearing a single end-effector of
      postconditioning does not exist. Perhaps, that there are several effectors
      ensured cardioprotective effect of adaptive phenomenon of postconditioning.

PMID- 24459868
TI  - [The action of ionotropic glutamate receptor channel blockers on effects of sleep
      deprivation in rats].
AB  - The action of non-competitive glutamate receptor antagonists on the effects of
      sleep deprivation has been studied on Krushinskii-Molodkina rats having an
      inherited predisposition to audiogenic seizures and Wistar rats deprived to this
      respond. Two types of glutamate receptor open channels blockers were used: the
      selective blockers of NMDA-receptors (memantine and IEM-1921) and blockers of
      mixed type, impacting both on the NMDA- and presumably Ca(2+)-permeable
      AMPA/kainate receptors (IEM-1754 and IEM 1925). Rats were subjected to 12 hours
      long sleep deprivation. Immediatly after that memantine and IEM-1921 were
      injected, and during the first 3 hours the total or partial reduction of fast
      wave (paradoxical) sleep and a significant increase of the representation of
      wakefulness at the cost of reducing the total time of slow-wave sleep were
      observed. These effects are most likely to be a consequence of the blockade of
      NMDA-receptors functioning in the systems of the rat brain responsible for the
      launch and maintenance of fast-wave sleep. Injection of IEM-1754 and IEM-1925 on
      background of sleep deprivation did not affect the organization of sleep during
      the first 3 hours of their action. During the second three-hour period the
      rebound effect was observed. The obtained results indicate the involvement of
      NMDA glutamate receptors in the functioning of various parts of the sleep system
      of both rat lines.

PMID- 24459869
TI  - [Reproduction of images present in different phases of alpha wave].
AB  - It is considered that sensitivity of cortical perceptive mechanisms changes
      simultaneously with alternation of alpha-rhythm phases and it affects visual
      recognition accuracy. To verify this statement we detected alternation of alpha
      wave phases online for sending stimuli in the middle of increase-phase or in the
      middle of decrease phase with high precision. 15 healthy volunteers (5 male and
      10 female) were observed. They also took tests to measure anxiety, extraversion
      and neurotism levels. Visual area O2 with maximum amplitude of alpha rhythm was
      used to control the stimulation. We compared reproduction (by hand drawing) after
      presenting sample lines in different alpha-wave phases, successfulness during
      copying of the samples of different lengths was also compared. Most volunteers
      (14 out of 15) reproduced reduced lines in comparison with samples after
      stimulation bound to either of two alpha-wave phases. This effect is less
      prominent during decrease phase (positivation), i.e. lines are drawn longer and
      match the sample better, than during the increase phase (especially for long
      sized samples). This impact of different conditions on task performance is less
      manifested in volunteers with low psychoemotional stability.

PMID- 24459870
TI  - [Different mechanisms of long-term synaptic facilitation during associative
      learning and sensitization].
AB  - The translation and transcription processes involved in mechanisms of synaptic
      plasticity during the development of conditional taste aversion were studied in
      command neurons LP11 and PP11 of defensive behavior in snail Helix lucorum. In
      control snails it was found that the combined presentation of gustatory (carrot
      juice) and supporting (concentrated solution of quinine) stimulus led to a change
      in neuron's responses to sensory stimulus, which are typical as to conditioning
      and also to the corresponding sensitization. 1 h after the start of training it
      was occurred facilitation of the responses to sensory chemical stimulus (weak
      solution of quinine) whereas 1.5 hour--reactions to the conditioned food
      stimulus. Application of the protein synthesis inhibitor cycloheximide during
      conditioning led to the suppression of response facilitation to both stimulus-
      weak solution of quinine and the conditioned food stimulus. However, application
      of the RNA synthesis inhibitor actinomycin D to the neurons caused selective
      suppression of synaptic facilitation in responses to sensory stimulation with a
      weak solution of quinine, but it had no effect on synaptic facilitation in the
      responses to the conditioned stimulus. It has been suggested that the development
      of conditioned taste aversion in snails causes a long-term synaptic facilitation
      in nerve cells LP11 and PP11 typical to the process of conditioning and
      sensitization, for the induction of which the variety of molecular genetic
      mechanisms are necessary.

PMID- 24459871
TI  - [Combined blockade of AMPA- and NMDA-receptors has maximum effect to eliminate
      development of pentylenetetrazole-induced kindling in rats].
AB  - Peroral chronic administration the standard antiepileptic drug sodium valproate
      in a dose of 200 mg/kg eliminates development of generalized clonic-tonic
      pentylenetetrazol kindling seizures in 100% of rats, but only in 57% of rats this
      treatment prevents clonic kindling seizures. In the specified dose sodium
      valproate decreases in 1.7 times average severity of pentylenetetrazol kindling
      seizures compare with control. IEM-2121, causing combined blockade of NMDA- and
      AMPA-glutamate receptors, as well as IEM-1676, which also blocks AMPA-, NMDA- and
      N-cholinoreceptors, both after peroral chronic administration in a doses 10 mg/kg
      and 20 mg/kg accordingly, possess higher, than sodium valproate, anticonvulsant
      activity because reduce average severity of pentylenetetrazol kindling seizures
      in 2.4-2.7 times in comparison with control and prevents clonic kindling seizures
      in 87% of rats. Combined blockade of AMPA- and NMDA-receptors and perhars N
      cholinoreceptors has maximum effect to eliminate epileptogenesis both clonic, and
      clonic-tonic pentylenetetrazol kindling seizures.

PMID- 24459872
TI  - [Integration of monovalent ion fluxes across plasma membrane under the balanced
      state: ion gradients and water balance in animal cells].
AB  - Interrelationships between monovalent ion transport, the membrane potential, and
      intracellular ion and water content of an animal cell are analyzed by computation
      of the balance of ion fluxes across the plasma membrane when the sodium pump and
      electroconductive channels operate in parallel with NKCC or Na-Cl (NC) symport.
      The behavior of the system is described in terms of the integral permeability of
      Cl- channels, the activities of NKCC or NC symport and two dimensionless
      parameters characterizing the activity of the Na/K pump relative to that of
      electroconductive channels. The latter two parameters are shown to largely
      determine the plasma membrane potential and intracellular concentration of K+ and
      Na+ whereas NC and NKCC symports and the permeability of Cl- channels regulate
      cell water balance and only slightly influence the intracellular K+/Na+ ratio and
      membrane potential.

PMID- 24459873
TI  - [Glucose absorption in the rat small intestine in vivo after various levels of
      local substrate load].
AB  - In order to evaluate relative roles of various mechanisms of glucose transport in
      the small intestine at high substrate loads in chronic experiments on rats, we
      investigated kinetics of glucose absorption in isolated part (-20 cm) of the
      intestine after its perfusion for 6 and 14 days during 1.5 h per day with 125 mM
      glucose solution (gr. 1--increased substrate load) or during 45-60 min per day
      with 25 mM glucose solution (gr. 2--reduced substrate load). The results of the
      experiments were analyzed by means of mathematical simulation. It was found that
      in the rats of gr. 1 the regular substrate load was more effective in maintaining
      a high level of glucose absorption in the isolated part of the intestine.
      Adaptation of glucose absorption to the increased local glucose load occurs due
      to enhancement of the secondary active transport via SGLT1. This component in
      many times exceeds the "unsaturated" component of glucose absorption, which is
      mainly determined by the facilitated diffusion via GLUT2, both at high and low
      glucose concentrations in the intestinal lumen.

PMID- 24459874
TI  - [RPE melanosomes bind A2E fluorophore of lipofuscin granules and products of its
      photooxidation].
AB  - The ability of melanosomes from human, bovine and frog retinal pigment epithelium
      cells (RPE) to bind A2E fluorophore of RPE lipofuscin granules and products of
      A2E photooxidation is investigated. RPE melanosomes are found to bind A2E
      molecules themselves as well as the molecules formed after A2E irradiation by
      visible light. In our experiments single melanosome was able to bind up to 0.08
      fmol A2E. Antioxidant activity of melanosomes is compared to antioxidant activity
      of their complexes with A2E. It is shown by luminal chemiluminescence quenching
      in the presence of hydrogen peroxide that in A2E/melanosomes complex the
      chemiluminescence quenching is not significantly reduced. Comparison of
      inhibitory activity of melanosomes and their complexes with A2E on UV-induced
      (light conditions) and Fe(2+)-ascorbate-induced (dark conditions) peroxidation of
      photoreceptor outer segments (POS) demonstrated that bound A2E does not affect
      inhibitory ability of melanosomes in both systems. Thus, binding of A2E to RPE
      melanosomes in concentrations from 0.01 to 0.1 fmol A2E per melanosome does not
      significantly alter their antioxidant properties. It is supposed that both A2E
      and hydrophilic products of its photooxidation could be bound by RPE melanosomes
      and, thus, it lost the ability to exhibit toxic properties.

PMID- 24459875
TI  - [Participation AMPK in the regulation of skeletal muscles metabolism].
AB  - Enzyme AMPK is a part of the family of serine/threonine specific protein kinases.
      AMPK plays important role in the transfer extracellular signals through
      phosphorylation of multiple substrates in different metabolic reactions of
      skeletal muscles. AMPK is geterotrimetric complex, consisting of the catalytic
      subunit (AMPKalpha) and two regulatory subunits (AMPKbeta and AMPKgamma), which
      are encoded by seven different high-homologous genes (alpha1, alpha2, beta1,
      beta2, gamma1, gamma2, gamma3). AMPK regulates skeletal muscle metabolism through
      phosphorylation of various enzymes such as carbohydrate, lipid and protein
      metabolism, as well as factors of transcription and initiation. The AMPK
      expression occurs in response to a changing metabolic requests muscle cells and
      it leads to increased energy metabolism. The data of recent studies suggest the
      important role of AMPK in the regulation of intracellular metabolism and point to
      the need to study the molecular mechanisms involved in the regulation of gene
      expression in skeletal muscle.

PMID- 24459876
TI  - [The role of the basal forebrain cholinergic dysfunction in pathogenesis of
      declarative memory disorder in Alzheimer's disease].
AB  - Alzheimer's disease is the most common cause of the declarative memory disorder:
      30-40% cases of dementia among all of age groups, and 50-60% among the people
      older 65 years. In addition, disorder of declarative memory is the genuine
      symptom of the disease, which certainly appears on early stage of the disease and
      it is an obligate diagnostic symptom. Proponents of the "cholinergic theory" of
      pathogenesis of Alzheimer's disease suggest that the basis disorder of
      declarative memory is cholinergic dysfunction. Several neurodynamic mechanisms
      associated with declarative memory depend on the level of acetylcholine in
      hippocampus and neocortex. It is believed that dysfunction of the basal
      cholinergic system in Alzheimer's disease leads to the impairment of these
      mechanisms. In this review, we summarize available literature data concerning the
      mechanisms of Alzheimer's disease.

PMID- 24459877
TI  - [Functional tests for the assessment of the healthy people state using heart rate
      variabilIty].
AB  - An overview of current approaches to interpreting the results of spectral
      analysis of heart rate variability and blood pressure is demonstrated. The
      analysis of own obtained results were done using the method of assessment of
      heart rate variability and blood pressure in a variety of functional tests
      (mental load, moderate exercise, cold test, the restriction of pulmonary
      ventilation, controlled breathing at a frequency of 6 cycles per minute) in
      healthy adults. It was shown that all tests induced pronounced changes in the
      spectral indices of heart rate variability as well as the blood pressure, which
      were interpreted as changes in the state of autonomous regulation of subject's
      cardiovascular system. The direction and the degree of changes depend on the form
      of action.

PMID- 24459878
TI  - [Redirection and consolation in hamadryas baboons].
AB  - Post-conflict interactions between victims and non-involved group members was
      investigated in the troop of hamadryas baboons, Papio hamadryas. Observations
      were done in the Russian Primate Center, Adler in 1996-1997. Redirected
      aggression, initiation of affiliation from the side of victims towards third
      parties and consolation were registered during this study. The analyses was done
      on 445 PC-MC pairs of animals, represented different social classes (harem male
      female pairs, harem females, relations, females from different harems, male-male
      pairs, female-subadult pairs). The attracted-pairs method and the time-rule
      method were used. Redirected aggression was practiced mainly by male aggressees.
      It was typical for victims, both males and females, to initiate affiliative
      interactions with third parties soon after the conflict. Consolation was
      practiced by hamadryas baboons, but it was limited to harem male-female pairs
      only. Special affiliative patterns were used by male-consoler. This is the first
      case, when consolation was demonstrated in baboons.

PMID- 24459879
TI  - [Geometrical images of coherent interrelations of biopotentials of EEG different
      frequency ranges in dynamics of humans goal-directed behavior].
AB  - Spatial organization of teta, alfa, beta-1, beta-2 in EEG potentials in humans
      who quickly an with a high accuracy performed task to learn and reproduce on PC
      monitor a definite sequence o accuracy performed task to learn and reproduce on
      PC monitor a definite sequence of circles wer studied. It was found that
      geometric images of coherent interrelations of teta, alfa, beta-1, beta-2 in EEG
      potentials were dynamically changed on the different stages of goal-directed the
      humans activity. The studies give the grounds to consider dynamically changed
      geometrical images of coherent links of different EEG potentials as an objective
      index of external projection of intracerebral processes of system architectonics
      of goal-directed behavior on brain cortex.

PMID- 24459880
TI  - [The influence of constant lightening on physiological parameters of rats
      homeostasis depending on time beginning of exposure].
AB  - The influence of constant lightening on biomarkers of ageing and rates of male
      rats aging was studied. It was revealed that the maintenance of rats in the
      constant lightening regime starting from the age of one month results in
      accelerated ageing of the organism, the reduction of the phases progressive and
      stable growth, early occurrence of presenile and senile periods, to the earlier
      occurrence of water-and-salt metabolism imbalance, accelerate the process of
      "aging" of the antioxidant system in comparison with the rates of the control
      group. On the contrary, the maintenance of rats in the constant lightening regime
      starting from the age of fourteen months slows ageing of the organism, increases
      body growth, delays appearance of pathological changes in the urine, slows down
      the "aging" of the enzymatic components of the antioxidant system.

PMID- 24459881
TI  - [Infradian rhythms of the thymic morphofunctional state in male Wistar rats].
AB  - We carried out a prolonged investigation of thymic cells, melatonin and
      corticosterone biorhythms in male Wistar rats. The total number ofthymic cells,
      lymphocyte numbers in the peripheral blood and percentrage of CD3+ lymphocyte had
      a 6-days period of fluctuation. The other period of fluctuation in 4 days was
      found in the dynamics width of subcapsular layer of the thymus and inclusion of
      the thymidine label. Biorhythms of the melatonin and corticosterone levels were
      in on antiphase and had a 4-days period.

PMID- 24459882
TI  - [Reparative regeneration of rat soft tissues is affected by a wound-healing
      composite].
AB  - We researched influence of original wound-healing composite, including chitosan
      and nanoparticles of copper and zinc, on specific of reparative regeneration of
      an experimental soft tissue full layer rat's wounds, which were conditionally
      aseptic and infected. The composite stimulation of reparative regeneration is
      related both to its antibacterial effect, and to the influence on the state of
      structural biopolymers of the connecting tissue.

PMID- 24459883
TI  - [Modeling of different degrees of microvessel laser-induced endothelium damage].
AB  - A comparative analysis of rat mesentery micro vascular reactions on thermal
      impact during radiation to the focused laser irradiation in UV and visible
      regions of spectrum is made. Local intravascular temperature rise during laser
      irradiation both impulse (lambda = 337 nm) and continuous (lambda = 532 nm)
      states causes thrombus formation. The thrombus development that determined by
      laser irradiation parameters gives a possibility to modulate different degrees of
      microvessel endothelium damage.

PMID- 24459884
TI  - [Lipid peroxidation in the immobilization stress of different duration].
AB  - It was demonstrated in experiments on rats, that increase of immobilization
      stress duration causes more prolonged activation of lipid peroxidation, however
      significant differences of both malonic dialdehyde and acylhydroperoxides content
      were not established in early period after stress in rats, which were exposed to
      the immobilization of different duration. It was shown, that increase of
      superoxiddismutase activity is observed in early period of 3-hour and 6-hour
      stress, but it was decreased in 12-hour immobilization. Catalase activity was
      decreased in 6-hour and 12-hour stress. These results confirm the literature data
      about dependence between the expression of stress manifestations and the strength
      and duration of stress factor action.

PMID- 24459885
TI  - [Mechanisms of coronary flow recovery in the isolated heart during reperfusion
      with cardioprotective liposomal emoxipin form].
AB  - In the experiments on the isolated perfused rat heart the effects of liposomes,
      containing different concentrations (0.25 and 0.1 mg/mL) of emoxipine, on
      coronary flow restoration after total normothermic ischemia and reperfusion were
      studied. The coronary flow, levels of nitrates and nitrites in the outflowing
      perfusate from heart and level of free radical processes were assessed, The
      obtained results showed that 0.1 mg/mL liposomal emoxipine provide with stronger
      increase coronary flow during reperfusion mostly due to the increase
      concentration of endothelial nitric oxide compare with treatments at 0.25 mg/mL.

PMID- 24459886
TI  - [The features of postsynaptic currents in primary culture of rat cortical
      neurons].
AB  - The generation features of postsynaptic currents were studied in primary culture
      of cortical neurons at 7-20 days in vitro (DIV). The use of specific blockers of
      postsynaptic ion channels after 10 DIV revealed all types of electrical activity
      found in adult cortex including miniature inhibitory (mIPSCs), excitatory
      (mEPSCs) and spontaneous giant excitatory currents and spikes. The frequency of
      mEPSCs increased exponentially from 7 to 20 DIV doubling every 2.2 days in
      parallel with changes in action potentials generation. The mEPSCs generated by
      NMDA and AMPA or by only AMPA receptor activation were found. The inhibition of
      NMDA receptors by magnesium ions or AP5 were shown to modulate the frequency and
      amplitude of mEPSCs, which differ primary culture from brain slices possibly
      because of the lack of glial control of synaptic transmission.

PMID- 24459887
TI  - [Assessment of validity of the archived standard curve in endotoxin assay].
AB  - The archived standard curve of endotoxin assay was evaluated to be possible to be
      used for the endotoxin assay as the reliable standard curve, instead the standard
      curve was produced each time of the assay. The archived standard curve shall be
      produced from three standard curves for three days, following the guidance issued
      from FDA in 1991, and the evaluation whether the archived standard curves can be
      applicable to use daily was performed with the recovery rate of the
      concentrations obtained from the archived standard curves against the true
      values. The three case studies were prepared: (1) the same person, who prepared
      the archived standard curves, performed this assay with the standard solutions
      (repeatability condition with the same tester, at the same facility), (2) the
      person, who did not prepare the archived standard curves, performed this assay
      with standard solutions (reproducibility condition with the different tester and
      dates), (3) the same preparation as (1), but using different three lots of
      lysates. The recovery rates were (1) 85-127%, (2) 86-124%, (3) 64-156%,
      respectively. From this data, the endotoxin concentration calculated with the
      archived standard curves were not varied very much, compared to the true values,
      but further discussion are necessary when the archived standard curves would be
      applied in daily analysis of PET drugs, regarding the protocol, the requirement
      to use the archived standard curve and the daily internal control as system
      suitability tests.

PMID- 24459888
TI  - [The effect of environmental factors and DNA methylation on type 2 diabetes
      mellitus].
AB  - Type 2 diabetes mellitus (T2DM) is a glucose metabolic disorder driven by both
      genetic and environmental factors. Recent DNA methylation studies have
      established that T2DM may be contributed by environmental factors through the
      regulation of DNA methylation. Human and animal model studies have made much
      progress on the interaction between DNA methylation of T2DM genes and
      environmental factors in multiple tissues. Current studies on DNA methylation of
      T2DM genes mainly focus on glucose and energy metabolism, inflammation, and so
      on. This review comprehensively introduces the DNA methylation studies for the
      genes involved in T2DM and its related environmental factors.

PMID- 24459889
TI  - [The effect of microRNAs on the regulatory network of pluripotency in embryonic
      stem cells].
AB  - Embryonic stem cells (ESCs) are pluripotent stem cells characterized by their
      ability to self-renew and their pluripotency to differentiate into all cell
      types. MicroRNA (miRNA) is a small non-coding RNA molecule which can regulate
      transcriptional and post-transcriptional gene expression, and may also play
      significant roles in regulating proliferation and differentiation of ESCs. The
      maintenance of pluripotency in ESCs may involve a regulatory network of many
      factors and pathways regulated by miRNA, which includes ESCs transcription
      factors, cell cycle regulation, epigenetic modifications as well as intracelluar
      signal transduction. This review mainly elaborates the biogenesis of miRNA, the
      miRNA families regulating the pluripotency of ESCs, and the effect of miRNA on
      the regulatory network of pluripotency in ESCs.

PMID- 24459890
TI  - [Peach genomics and genome-wide association study: a review].
AB  - Peach (Prunus persica (L.) Batsch) is one of the most predominant stone fruits in
      Rosaceae family. The broad climate adaption, diverse cultivation region and good
      fruit taste make it one of the favorate fruits by consumers. Improving fruit
      quality and enhancing disease/pest resistance are always a focus for peach
      genetists and breeders to follow with interests. This paper reviews the main
      achievements on linkage map and physical map construction, development of various
      molecular markers, whole genome sequencing and transcriptome sequencing for peach
      in recent years, and also elaborates the applications of genome wide association
      study (GWAS) with high density SNP markers in peach and other plant crops. This
      review also provides a theoretical basis for GWAS analysis in the future study to
      identify high efficient markers of targeted traits for peach.

PMID- 24459892
TI  - [Structure and function analysis of Arabidopsis thaliana SRO protein family].
AB  - Many biotic and abiotic stresses can cause oxidative stress in plants. The
      identification of components involved in plant response to oxidative stress has
      attracted wide attention. The members of AtSRO family, including AtRCD1, AtSRO1,
      and AtSRO5, regulate plants' response to oxidative stress. AtSROs participate in
      plant normal growth and development, and play important roles in plant response
      to stresses, such as drought, salt, heavy metal, and so on. In addition, AtSROs
      possess some special domains, including PARP and RST. It is speculated that
      AtSROs may function in regulating protein transcription, adjustment, and
      modification. This review highlights some recent progresses, such as basic
      situation of AtSROs, effects of AtSRO family proteins on plant growth and
      response to abiotic stress, which will provide a theoretical basis for further
      studying on biological functions of AtSRO.

PMID- 24459891
TI  - [Biological functions of HD-Zip transcription factors].
AB  - The HD-Zip transcription factors, which are unique to plant kingdom, belong to
      Homeobox proteins. They are composed of highly conserved HD (Homeodomain) and Leu
      zipper (Zip) element. The former binds specifically to DNA and the later mediates
      the formation of dimerization. Based on the structure features, HD-Zip
      transcription factors can be classified into four subfamilies HD-Zip I - IV,
      which are involved in different biological processes of plants including growth
      and development, photomorphogenesis, flowering, fruit ripening, and adaptation
      response to environmental stresses. HD-Zip transcription factors act as the
      integrators of development and environmental cues and endogenous hormone signal
      pathway to regulate targeted gene expression and plants adaptation response. In
      this review, the most advanced researches on biological functions of HD-Zip were
      summarized based on the researches of Arabidopsis HD-Zip transcription factors
      and the results from other species. The aim of this article is to provide the
      basis for studying the functions of new genes encoding HD-Zip proteins from other
      species and illustrating the molecular mechanism of HD-Zip on growth and
      development of plant under normal and unfavorable conditions.

PMID- 24459893
TI  - [Comparative analysis of conservation and regulatory network on core
      transcription factors in mouse inner ear development].
AB  - During vertebrate inner ear development, several core genes, such as Six1, Six4,
      Pax2, Pax8, Foxi1, Dlx5, Gbx2, Irx2/3, and Msx1, are crucial to the regulation of
      the otic placode induction. In order to get the gene regulatory network during
      inner ear development, bioinformatics methods were adopted to analyze
      conservation and regulation of the core transcription factors in mice. Pax2,
      Pax8, Foxi1, and Dlx5 remained to be the main regulators during inner ear
      development, which was consistent with the gene regulatory network from
      literature. Six1 was regulated by many transcription factors, and Gbx2, Irx2/3,
      and Msx1 played important roles in the regulatory network. The differences in the
      constructed regulatory network were reasonably analyzed. It was predicted that
      Msxl regulated the expression of Six1 and Gbx2. In addition, several
      transcription factors, such as Sox5, Lhx2, Rax, Otx1, Otx2, Pitxl, Pitx2, Nkx2-5,
      Irx4, Irx6, Dlx2, Hmx1/2/3, Pou4f3, Pax4 and Tlx2, were found to be involved in
      the regulatory network. Our results provide an improved understanding of the
      regulatory mechanism during inner ear development.

PMID- 24459894
TI  - [Correlation analysis between polymorphism of the 59383635th locus on X
      chromosome and fat-tail trait in sheep].
AB  - Fat tail or fat rump is one of essential traits for surviving in harsh
      environments, and the mechanism of fat deposition and its inheritable characters
      in sheep are still unclear. Therefore, the 59383635th locus on X chromosome in
      our unpublished chip data was chosen as candidate SNP, PCR-SSCP method was used
      to detect genotypes in five sheep breeds which have extreme differences in tail
      types (Altay, Small Tail Han Sheep, Hu, Chinese Merino and Suffolk), and the
      mathematical model was employed to analyze the correlation between the
      polymorphism and the trait of fat tail or fat rump. The results in this study
      showed that the high frequency of allele T exists in Altay flock, and the
      frequency of allele C appears to be particularly high in the thin tail sheep
      breeds. The result of mathematical model showed that the ratio of T/C increased
      exponentially with the increase of phenotype score. These results suggest that
      there is a big difference in the SNP distribution between fat tail (rump) and
      thin tail sheep populations, and the SNP can be used as an ideal molecular marker
      in high-fat or low-fat sheep breeding. However, the biological function of the
      SNP remains to be further studied.

PMID- 24459895
TI  - [Cloning and functional analysis of Phyllostachys edulis MYB transcription factor
      PeMYB2].
AB  - MYB-type transcription factor is one of the largest families in plants, which
      plays important roles in accepting stress signals from environment and regulating
      the expression of stress-tolerant genes. In this paper, using homologous cloning
      and RACE technology, a MYB-type transcription factor, designated PeMYB2, was
      cloned from Phyllostachys edulis. The results of bioinformatics showed that
      PeMYB2 is a typical R2R3-MYB. It contained two tandem repeats in its N-terminus,
      and a membrane protein DUF3651 in its C-terminus. In addition, phylogenetic
      analysis indicated that PeMYB2 shared the highest homology with 85.98% to OsMYB18
      protein from Oryza sativa spp. Japonica. In addition, a yeast one-hybrid assay
      showed that PeMYB2 could activate the expression of downstream genes. After
      PeMYB2 was transformed into Arabidopsis thaliana, seven PeMYB2 transgenic
      Arabidopsis lines were obtained. Phenotypic analysis of the transgenic and wild
      type Arabidopsis showed that over-expression of PeMYB2 caused delayed flower or
      dwarfism in transgenic Arabidopsis. Under the abiotic stress conditions, such as
      salt and cold stresses, the over-expression of PeMYB2 in Arabidopsis had higher
      survival rate than the wild-type Arabidopsis. Expression analysis of saline
      stress response marker genes in the transgenic and wild-type plants under the
      salt stress condition showed that PeMYB2 regulated the expression of NXH1, SOS1,
      RD29A, and COR15A. As the result, PeMYB2 might play an important role in various
      responses to abiotic stresses in P. edulis.

PMID- 24459896
TI  - [Analysis of cis-regulatory element distribution in gene promoters of Gossypium
      raimondii and Arabidopsis thaliana].
AB  - Cotton genomic studies have boomed since the release of Gossypium raimondii draft
      genome. In this study, cis-regulatory element (CRE) in 1 kb length sequence
      upstream 5' UTR of annotated genes were selected and scanned in the Arabidopsis
      thaliana (At) and Gossypium raimondii (Gr) genomes, based on the database of
      PLACE (Plant cis-acting Regulatory DNA Elements). According to the definition of
      this study, 44 (12.3%) and 57 (15.5%) CREs presented "peak-like" distribution in
      the 1 kb selected sequences of both genomes, respectively. Thirty-four of them
      were peak-like distributed in both genomes, which could be further categorized
      into 4 types based on their core sequences. The coincidence of TATABOX peak
      position and their actual position ((-) -30 bp) indicated that the position of a
      common CRE was conservative in different genes, which suggested that the peak
      position of these CREs was their possible actual position of transcription
      factors. The position of a common CRE was also different between the two genomes
      due to stronger length variation of 5' UTR in Gr than At. Furthermore, most of
      the peak-like CREs were located in the region of -110 bp-0 bp, which suggested
      that concentrated distribution might be conductive to the interaction of
      transcription factors, and then regulate the gene expression in downstream.

PMID- 24459897
TI  - [A cross-sectional study on urinary iodine and iodine content of salt among
      school children aged 8-10 years old in Yuhuan County, Zhejiang Province in 2012].
AB  - OBJECTIVE: To understand the level of urinary iodine and iodine content of salt
      among school children aged 8 to 10 years in Yuhuan County, Zhejiang Province.
      METHODS: A cross-sectional study was conducted in a primary school of Yuhuan
      County purposely selected in 2012. Totally, 450 children aged 8 to 10 years were
      involved by the cluster-stratified sampling. All subjects received a free
      physical examination and morning urine and salt using in the household were
      collected. Urinary iodine and the iodine content of salt the children were
      tested. RESULTS: Totally, 449 of 450 children provided the morning urine enough
      to be tested. The median of children's urinary iodine was 114.0 microg/L, and the
      proportions of them with the urinal iodine < 50 microg/L, < 100 microg/L and > or
      = 300 microg/L were 4.4%, 37.9% and 2.7%, respectively. Among 447 salt samples
      collected, the median of iodine content was 0.0 mg/kg. The coverage rate of
      iodized salt was 27.3%, the qualified rate of iodized salt was 92.6%, and the
      intake rate of qualified iodized salt was 25.3%. The median of urinary iodine of
      children with iodized salt was significantly higher than that of those without
      iodized salt (Z = 3.47, P = 0.001). CONCLUSION: Current nutritional status of
      iodine is overall proper and safety in the population of school children aged 8
      10 years old in Yuhuan County.

PMID- 24459898
TI  - [Effect of maternal high fat diet during gestation and lactation period on
      spatial learning and memory in adult mice offspring].
AB  - OBJECTIVE: To investigate the effect of perinatal high fat diet on spatial
      learning and memory in adult Kunming (KM) mice offspring. METHODS: The adult
      female KM mice were randomly divided into control and high fat group, fed with
      lab chow and high fat diet (containing 20% of lard) during gestation and
      lactation periods. After weaning at 4 weeks old, 10 offspring mice randomly
      selected from control group, as control continuing (CC) group, were fed with lab
      chow. 10 mice, as high fat continuing (FF) group, from high fat group were fed
      with high fat diet. 10 mice, as transforming high fat (FC) group, were fed with
      lab chow. Then, Morris water maze task was applied to evaluate spatial learning
      and memory in the pups. The body weight and the mass of visceral fat and brain
      were weighted, and the level of serum leptin was measured through ELISA. RESULTS:
      Latency of FF and FC groups were shorter than CC group (P < 0.05), and the
      crossing times of FC group was more than CC group. The weights, the mass of
      visceral fat and brain of FF and FC groups were heavier than those of control
      group (P < 0.05). The level of serum leptin of FF group was higher than CC group
      (P <0. 05). CONCLUSION: Maternal high fat diet during pregnancy and lactation may
      contribute to better spatial learning and memory ability in adult mice offspring.

PMID- 24459899
TI  - [Effects of oils on lipid metabolism in obese C57BL/6J mice induced by a high fat
      diet].
AB  - OBJECTIVE: To investigate and compare the effects of oils on lipid metabolism in
      obese C57BL/6J fed a high fat diet. METHODS: 75 male C57BL/6J mice (4-5 weeks
      old) were used and randomly divided into 5 groups, 15 mice in each group, and
      were fed a high fat diets with 2% soybean oil, medium-chain triglyceride (MCT),
      peanut oil, olive oil and tea seed oil respectively for 12 weeks. Body weight,
      body fat, diet intake, blood lipid profiles and enzymes relevant to lipid
      metabolism in white adipose tissue (WAT) as well as pathologic changes in WAT and
      livers from all groups were observed and compared. RESULTS: At the end of study,
      the body weight and body fat weight were significantly lower in MCT, peanut oil,
      olive oil, tea oil groups than in soybean oil group (P < 0.05). The mice in MCT
      group showed significantly lower TG, TC, LDL-C in serum and lower TG, TC in liver
      than those in soybean oil group (P < 0.05). The cAMP, PKA, HSL, ATGL in WAT in
      MCT group showed higher than those in soybean oil group (P < 0.05). There was no
      fatty infiltration in the livers of mice fed MCT, olive oil and tea oil group,
      but visible fatty liver in soybean oil and peanut oil group were found.
      CONCLUSION: Compared to soybean oil, MCT, peanut oil, olive oil and tea oil could
      reduce body weight and body fat weight in obese mice fed a high fat diet, MCT
      also decreased TG, TC, LDL-C in serum and promote lipid mobilization in WAT. As
      to improving blood lipids, olive oil and tea oil were less obvious than MCT was,
      and both oils did not induce significant fatty liver when compared with soybean
      oil and peanut oil.

PMID- 24459900
TI  - [Screening of urinary biomarkers in patients with type 2 diabetes mellitus].
AB  - OBJECTIVE: To screen the biomarkers of the middle-aged type 2 diabetes (T2DM) in
      urine based on metabolomics. METHODS: First, both the metabolite profiles of
      morning urine sample in T2DM and control group were obtained by liquid
      chromatography-mass spectrometry (LC-MS). Second, an automated compound (feature)
      extraction algorithm was employed for processing background subtracted single MS
      data. Then principal component analysis (PCA) and t-Test analysis was followed
      after preprocessing on the extractive data. Third, identifying the potential
      biomarkers that show significant difference between the two groups by searching
      the database online and comparing the results of MS/MS experiments to those
      available in literature and those standards. RESULTS: Three endogenous
      metabolites, among which tryptophan, kynurenic acid, and shown down-regulation
      while kynurenine shown up-regulation in T2DM, significantly differentiate between
      T2DM and control group. CONCLUSION: Tryptophan, kynurenic acid and kynurenine may
      be considered as the potentail biomarkers related to T2DM.

PMID- 24459901
TI  - [Effects of cell malignant transformation induced by benzo[a]pyrene on DNA
      methylation transferases].
AB  - OBJECTIVE: To investigate the expression level and enzymatic activity of DNA
      methylation transferases (dnmts) in mouse embryonic fibroblast malignant
      transformed cells induced by benzopyrene (B[a]P). METHODS: Two kinds of cell
      lines, pol beta wild-type cells (pol beta +/+) and malignant transformation cells
      induced by BaP (pol beta-T) were applied as cellular models. Pol beta +/+ cells
      were served as controls, RT-PCR and Western blot were used to measure the change
      of dnmts expression level in malignant transformation cells induced by BaP. The
      enzymatic activity of DNMTs was also detected with DNA methyltransferase (DNMT)
      activity/inhibition assay kit. RESULTS: The mRNA and protein expression levels of
      dnmt1 and dnmt3b in pol beta-T cells (0.940 +/- 0.033 and 0.905 +/- 0.062) were
      much higher than that in pol beta +/+ cells (0.560 +/- 0.031 and 0.666 +/-
      0.041), however the expression level of dnmt3a had no difference between these
      two cell lines. On the contrary, the enzymatic activity level of DNMTs in pol
      beta-T cells ((329.48 +/- 52.11) OD x h(-1) x mg(-1)) was much lower than that in
      pol beta +/+ cells ((253.70 +/- 20.56) OD x h(-1) x mg(-1)). CONCLUSION: The over
      expression of dnmt1 and dnmt3b and the change of DNMTs activity may be contribute
      to the cell malignant transformation process induced by BaP.

PMID- 24459902
TI  - [Expression and identification of recombinant Staphylococcus aureus enterotoxin
      A].
AB  - OBJECTIVE: To clone the sequence of Staphylococcus aureus enterotoxin A (SEA)
      gene, construct its expression vector, and obtain high levels of recombinant
      Staphylococcus aureus enterotoxin A (rSEA) with high purity. METHODS: The
      enterotoxin A gene was synthesized and inserted into the prokaryotic expressed
      vector pET28a possessing histiding-tag. The recombinant vector was transfected
      into E. Coli BL21 (DE3) after it had been verified by DNA sequencing. The strain
      can express the recombinant protein after the induction by the IPTG. The
      recombinant protein was purified by Ni-NTA His Bind affinity purification column.
      RESULTS: The recombinant protein was obtained. SDS-PAGE showed that its molecular
      mass was about 30kD. The western bolt showed that it can specifically bind rabbit
      anti-SEA antibody. The BALB/c mouse was immunized by the recombinant protein
      followed by detection of anti-SEA antibody by ELISA. The results revealed that
      the protein has reactogenicity and immunogenicity, which provides the foundation
      for either the preparation of monoclonal antibodies or the further study of the
      immunological detection of SEA. CONCLUSION: The rSEA expression vector was
      constructed successfully and highly expressed the rSEA protein.

PMID- 24459903
TI  - [Genetic characterization and antimicrobial susceptibility analysis of
      methicillin-resistant Staphylococcus aureus isolated from ready-to-eat food and
      pig-related sources in China].
AB  - OBJECTIVE: To study the mecA gene distribution in 877 strains of Staphylococcus
      aureus isolated from the environment of pig farm and slaughter house, pig carcass
      and its iliac lymph nodes, and ready-to-eat foods in China as to screen the
      methicillin-resistant Staphylococcus aureus (MRSA), and to evaluate the
      antimicrobial susceptibility of MRSA. METHODS: A total of 877 strains of S.
      aureus that had been phenotypically identified by Gram staining, catalase test,
      ability to coagulate rabbit plasma, API STAPH as well as analysis of nuc gene,
      encoding for a S. aureus specific thermonu-clease were screened for MRSA by
      characterizing the mecA gene. The antimicrobial susceptibility of MRSA was tested
      in accordance with the broth microdilution method recommended by the Clinical and
      Laboratory Standards Institute. RESULTS: Of 877 S. aureus strains tested, 71
      (8.1%, 71/887) were mecA positive and identified as MRSA, among which, 48
      isolates were pig-associated and 23 isolates were ready-to-eat food-associated.
      The frequency of pig-associated MRSA was significantly higher than that of food
      associated one (chi2 = 53.040, P < 0.01). All MRSA were susceptible to linezolid,
      vancomycin, tigecycline, and nitrofurantoin but resistant to cefoxitin, oxacillin
      and benzylpenicillin. Meanwhile, 98.6% (70 strains), 95.8% (68 strains), 88.7%
      (63 strains), 80.3% (57 strains), 80.3% (57 strains) and 32.4% (23 strains) MRSA
      exhibited the resistance to clindamycin, erythromycin, tetracycline,
      ciprofloxacin, trimethoprim/sulfamethoxazole, and gentamicin, respectively.
      Besides, one strain was resistant to each of antibiotics including levofloxacin,
      moxifloxacin, rifampicin, and quinupristin/dalfopristin. It was worth noting that
      the frequency of resistance to ciprofloxacin, tetracycline, and
      trimethoprim/sulfamethoxazole of pig-associated MRSA was significantly higher
      than that of food-associated MRSA (CIP: chi2 = 29.110, P < 0.01, TET: chi2 =
      18.816, P < 0.01, TMP/ SMZ: chi2 = 36.394, P < 0.01). It should be pointed out
      that 70 (98.6%) strains of MRSA were multi-drug resistant and eight spectrums of
      antimicrobial susceptibility were observed. CONCLUSION: The multi-drug resistant
      MRSA isolated from pig- and food-associated matrixin China is very serious.

PMID- 24459904
TI  - [Neurobehavioral derangement in medaka fish receiving polybrominated diphenyl
      ethers (PBDE-47) during the early-stage development].
AB  - OBJECTIVE: To investigate the neurobehavioral toxicity of polybrominated diphenyl
      ethers(PBDE-47) to larval medaka during the early-stage development. METHODS:
      Early-life stage fish were treated with PBDE-47, control, and solvent control.
      Animals were randomly collected on 5, 10 and 60 days after exposure, and some
      toxicological endpoints such as startle response, optokinetic response (OKR),
      optomotor response (OMR) and dorsal light response (DLR) were measured. RESULTS:
      There were no any significant difference in body weight gain or body length in
      the PBDE-47 treated medaka except for the highest concentration. Both startle
      response and escape response were inhibited in dose-related manners. Furthermore,
      delayed OMR and DLR were induced in the higher PBDE-47 groups (P < 0.05 or P <
      0.01). However, OKR was similar between the each group. CONCLUSION: Harmony of
      the sense-behavior in the medaka larvae could be impaired by PBDEs, and further
      study should focus on the relationship between the toxicity and hormone
      disruption caused by PBDE-47.

PMID- 24459905
TI  - [Protective effects of exogenous reduced glutathione on sodium arsenite-induced
      genotoxicity and oxidative stress].
AB  - OBJECTIVE: To explore the protective effects of exogenous reduced glutathione
      (GSH) on the genotoxicity and oxidative stress induced by sodium arsenite
      (NaAsO2). METHODS: Human lung adenocarcinoma A549 cells were divided into several
      groups according to the treatments as follow: untreated group, single NaAsO2 or
      GSH treated group and the groups co-treated with NaAsO2 and different
      concentrations of GSH. Then the differences of cell viability, level of oxidative
      stress, DNA and chromosomal damage were compared after single or combined
      treatments. RESULTS: The rate of cell survival and colony formation, the contents
      of GSH and the activity of SOD in NaAsO2 treated group were significantly lower
      than the non-treated group, whereas, the level of ROS, comet rate, OTM and the
      frequency of micronucleus in NaAsO2 treated group were significantly higher than
      that of control group (P < 0.05). At the 0.5-5 mmol/L concentrations of GSH,
      these indicators of the co-treatment groups did not show any significant
      difference when compared with single NaAsO2-treated group. However, at the 10
      mmol/L and 20 mmol/L concentrations of GSH, the NaAsO2-induced toxic effects were
      found to be weakened by GSH, but it was still significantly lower than that in
      the control group (P < 0.05). Moreover, there was no significant difference among
      co-treated groups and control group on the cell viability, colony formation,
      level of oxidative stress and DNA and chromosomal damage at the 40 or 50 mmol/L
      of GSH. CONCLUSION: High concentrations of exogenous GSH can significantly
      decrease the cytotoxicity of NaAsO2, and alleviate DNA and chromosomal damage and
      the level of oxidative stress.

PMID- 24459906
TI  - [Relationship of general self-efficacy, motivation and peer with refusal skills
      for no tobacco among adolescents].
AB  - OBJECTIVE: To explore the prevalence of each of the refusal strategies (refuse,
      explain, leave) as they apply to tobacco offers and the relationship of self
      efficacy, motivation and peer with tobacco refusal strategies. METHODS: A total
      of 641 students from four high schools in Baise cities, ranging in age between 14
      and 21 years, filled the general self-efficacy scale, smoking motivation
      questionnaire, refusal strategies questionnaire and peer questionnaire. RESULTS:
      Adolescents were more likely to use the refuse (77.69%) and leave strategy
      (58.81%) for initial tobacco offers and follow-up tobacco offers. There were
      significant differences of self-efficacy scores in both refuse and leave strategy
      (7.169/0.000 and 7.647/0.000). Significant differences of motivation were seen in
      refuse strategy for initial tobacco offers and for follow-up tobacco offers (P <
      0.05). Enhancement and social motivation showed significant differences in leave
      strategy for follow-up tobacco offers. The results of the logistic regression
      showed that self-efficacy was significant variable that predicted the use of
      explain strategy (beta = -0.078) and the use of leave strategy (beta = -0.081)
      for both initial tobacco refusals and follow-up tobacco refusals, while
      enhancement and coping motivation were significant for the use of leave strategy
      (beta = -0.621and beta = -0.303). CONCLUSION: There were significant effects of
      self-efficacy and motivation in effecting explain and leave strategies for
      tobacco refusals.

PMID- 24459907
TI  - [Longitudinal study on adolescents' psychological resilience and its impact
      factors in 5.12 earthquake-hit areas].
AB  - OBJECTIVE: To explore the trajectory of psychological resilience and its impact
      factors of adolescents in earthquake-hit areas by latent variable growth curve
      model (LGM) and to find out protective factors for psychological resilience.
      METHODS: Longitudinal design was administrated. All grade one students in two
      junior high schools in the heavily and slightly earthquake-hit areas respectively
      were investigated by follow-up study in one year. Repeated measures analysis of
      variance and latent variable growth curve model were used for statistical
      analysis. RESULTS: The three-time measurements of psychological resilience of
      adolescents in the heavily earthquake-hit areas were significantly lower than
      corresponding measurements of the slightly earthquake-hit areas all along. There
      was an ascending trend of adolescent's psychological resilience and objective
      support over one year (P < 0.05), while a descending trend of self-esteem (P <
      0.05). The directly protective factors of resilience were self-esteem and
      subjective support and indirectly protective factors were objective support and
      utilization of social support. The psychological resilience of boys was higher
      than that of girl, but the change trend of psychological resilience was no
      difference between boys and girls. CONCLUSION: Psychological resilience of
      adolescents had dynamic characteristics. Psychological resilience of adolescents
      would be damaged in disasters but it could be recovered through enhance internal
      and external protective factors.

PMID- 24459908
TI  - [Analysis of psychological resilience of left-behind high school students in
      Nanchong rural].
AB  - OBJECTIVE: To analyze the scores of psychological resilience of left-behind rural
      high school students and then provide the basis of mental health supporting for
      these students. METHODS: survey include multi-stage sampling, extracting a total
      of 1,000 students of all grades from two rural high schools, and letting them
      fill the questionnaire "New Resilience & Youth Development Module" within limited
      time. RESULTS: Contrast between students being left-behind for varying length of
      time and non-left-behind ones: school factors (36.57 +/- 8.62), internal factors
      (49.44 +/- 9.89), peer factors (16.78 +/- 3.82) and family factors (22.90 +/-
      7.56). Students being left-behind for varying length of time all score lower than
      non-left-behind ones, and the difference was statistically significant (P <
      0.05). Contrast between gender: left-behind high school girls score lower than
      left-behind high school boys and non-left-behind students in school psychological
      resilience (34.84 +/- 6.62), and the difference was statistically significant (P
      < 0.05). Contrast between different types of being left-behind and non-left
      behind: parents left-behind vs non-left-behind, and father-left-behind vs non
      left-behind-school factors (33.43 +/- 7.43 vs 39.70 +/- 8.12), social factors,
      internal factors, peer factors and family factors. Students of both types score
      lower than non-left-behind ones, and the difference was statistically significant
      (P < 0.05). CONCLUSION: The psychological resilience scores of left-behind high
      school students are lower than that of non-left-behind students. Therefore,
      effective measures is necessary to improve the psychological resilience of left
      behind rural high school students.

PMID- 24459909
TI  - [Beijing college students' self-consciousness: its level, structure and
      relationship with mental health].
AB  - OBJECTIVE: To investigate Beijing college students' self-consciousness and its
      relationship with mental health. METHODS: Convenient samples of 928 college
      students from five universities in Beijing were inquired and assessed with the
      self-consciousness scale and the Kessler 10 psychological distress scale.
      Confirmatory factor analysis and structural equation modeling were used to
      analyze the data. RESULTS: College students' scores of self-consciousness did not
      differ in sex, age, grade and major type. 83.5% of the participants had
      relatively low scores (10-24) of psychological distress, but those of the
      students of liberal arts were higher (P < 0.05). The measurement data of self
      consciousness supported Mittal and Balasubramanian' s five-factor structure. Self
      reflectiveness was positively correlated with depression (P < 0.05). Internal
      state awareness was negatively associated with both anxiety and depression (P <
      0.05). Style consciousness was positively correlated with both of them (P <
      0.001). CONCLUSION: Beijing college students' self-consciousness is relatively
      high and has a relatively complex structure. While self-reflectiveness and style
      consciousness have negative effects, internal state awareness is good for mental
      health.

PMID- 24459910
TI  - [Survey on iodine nutrition in high water regions of children, adult and the
      third trimester pregnant women in China].
AB  - OBJECTIVE: To investigate the iodine nutrition status of the susceptible
      population after stop supplying iodized salt and discuss whether there is iodine
      nutritional status difference in different populations in high-iodine areas in
      China. METHODS: Spot investigation methods were being used, 371 children, 506
      adults and 210 cases of pregnant women during the third trimester were selected
      as respondents. The morning Urine was collected to determinate the urine iodine
      level. Drinking water was collected to determinate the local water iodine level.
      RESULTS: The water iodine level was between 150.3-962.6 microg/L in investigation
      areas; The median urinary iodine (MUI) of children, adults and pregnant woman was
      respective 1032.08 microg/L, 1152.01 microg/L and 1240.70 microg/L. Meanwhile
      96.2% children and 93.1% adults urine iodine level was more than 300 microg/L and
      84.3% of pregnant women urine iodine level was more than 500 microg/L, which
      belongs to excessive iodine intake. The chi-square test on the distribution of
      urinary iodine indicate that there is statistical differences in three different
      population (chi2 = 44.84, P = 0.000). Kruskal-Wallis H test show that the MUI in
      three different crowd are not all the same (chi2 = 12.83, P = 0.002), when
      compared by pairs, the difference in MUI between pregnant and children or adults
      was founded. CONCLUSION: The iodine nutrition status of children, adult and the
      third trimester pregnant women in high water regions were iodine excess. The
      monitor on iodine nutrition status in different peoples should be enhanced.
      Urinary iodine level of Children can't completely represent the iodine
      nutritional status of pregnant women, iodine nutritional status monitor standard
      for pregnant women should be established.

PMID- 24459911
TI  - [Distribution of waist circumference and waist-to-height ratio for 7-18 children
      and adolescents in Gansu Province].
AB  - OBJECTIVE: To understand the percentile normal of waist circumference and waist
      to-height ratio for 7-18 children and adolescents in Gansu Province and to
      analyze their distribution and growth trend. METHODS: A stratified cluster
      representative sample of 6600 urban and rural children aged 7-18 years in Gansu
      Province was selected. To measure their waist circumference and height and
      establish the norm of waist circumference and waist-to-height ratio with
      percentile method. To compare them with the domestic correlation data. RESULTS:
      Sex-age specific percentiles of P5, P10, P25, P50, P75, P90, P95 of waist
      circumference and waist-to-height ratio for 7-18 children in Gansu Province were
      accessed. The P50 of waist circumference was increasing year by year and crossed
      two times, but that of waist-to-height ratio fluctuated slightly. A comparison of
      the P50 of the waist circumference and waist-to-height ratio among China, Peking
      and Gansu. Before 15 the data of Gansu were lower than those of China and
      Beiing;but were higher than that after 16. CONCLUSION: To have constructed
      percentile normal of waist circumference and waist-to-height ratio for 7-18
      children and adolescents in Gansu Province. The study provided a basic data for
      further studies of child and adolescent central obesity in China.

PMID- 24459912
TI  - [Case analysis of telephone interview application effect in Beijing].
AB  - OBJECTIVE: To apply Computer Assisted Telephone Interview (CATI) in evaluation on
      effectiveness of non-communicable diseases control and prevention among general
      population. METHODS: Totally 2450 permanent residents aged 15 to 69 years old
      were interviewed by telephone in Xicheng District and Changping District,
      Beijing. Telephone numbers were selected by simple random sampling. CATI was used
      to collect data. Focus group interview was used to interview telephone
      interviewers in order to analyze the reason of the midway refusal. RESULTS:
      93,524 telephone numbers were dialed. Survey efficiency, response rate and
      successful completion rate were 3.8%, 26.2% and 75.1%, respectively. The main
      cause resulting in low survey efficiency and response rate were no answer, busy,
      and refusal to answer at the beginning. The main cause which influenced
      successful completion rate was midway refusal to answer. CONCLUSION: Successful
      completion rate in this survey was high, so CATI is suitable for this survey.
      However, survey efficiency and response rate were too low. The emphasis was to
      reduce the proportion of no answer, busy and refusal in the beginning in order to
      improve the efficiency of this survey.

PMID- 24459913
TI  - [Effect of lead and selenium on learning and memory ability in rats].
AB  - OBJECTIVE: To study the effect of lead and (or) selenium on learning and memory
      ability in rats. METHODS: SPF Wistar rats, after weaning, were divided into six
      groups, control group, Pb group (respectively Pb exposed), Se group (respectively
      Se added), Pb-Se group (added Se after Pb exposure), Se-Pb group (added Se before
      Pb exposure) and Pb + Se group (Pb and Se exposed simultaneously). After
      intervention for six weeks in rats, the spatial learning and memory of each group
      rats were measured by Morris water maze assay. RESULTS: Rats in Pb group had
      significantly longer latency, less site crossings, less percentage of time and
      distance spent in the target quadrant, and bigger first bearing compared with
      control group (P < 0.05). Rats in Pb and Se joint exposure groups had
      significantly shorter latency, more site crossings, less percentage of time and
      distance spent in the target quadrant, and smaller first bearing compared with Pb
      group (P < 0.05). There were no significant differences in the indexes of spatial
      learning and memory ability between the groups of lead and selenium joint
      exposure groups (P > 0.05). CONCLUSION: Lead damaged the ability of learning and
      memory in rats and organic selenium had protective effects on Pb-induced spatial
      learning and memory deficits in rats.

PMID- 24459914
TI  - [Development and application of real-time PCR for identification and detection of
      horse meat in animal-origin products].
AB  - OBJECTIVE: To develop a real-time PCR method for identification and detection of
      domestic horse meat (Equus caballus) in animal-origin products. METHODS: The
      primer and TaqMan-probe was designed and synthesized according to the EU
      reference laboratory and 87 bp fragments was amplified for horse ingredients. The
      specificity and sensitivity was tested by artificially spiked horse meat into
      other domestic meat, such as cattle, sheep, pork, chicken, duck and rabbit. 122
      samples of cattle and sheep products were random collected in Beijing market and
      the detection of horse meat was carried out. RESULTS: The real-time PCR in this
      study has high specificity and sensitivity for horse meat. No cross-reaction was
      observed between the horse and sheep, pork, chicken, duck and rabbit meat. There
      was little cross reaction between horse and cattle when the CT value reach 33.
      81. The method can detect 0.1% of horse meat mixed with other domestic animal
      origin products. No horse meat ingredients were detected in 122 samples in this
      survey. CONCLUSION: There was no horse meat mixed into cattle and sheep products
      in Beijing marked.

PMID- 24459915
TI  - [Inhibitory effect on Microcystis aeruginosa as well as separation and
      identification of the allelochemicals of welsh onion].
AB  - OBJECTIVE: To study the inhibition of welsh onion on Microcystis aeruginosa, and
      separat and identify of the allelochemicals from welsh onion. METHEDS: The
      inhibitory effect of different concentrations of fistular onion stalk and
      fistular onion leaf water extracts on M. aeruginosa were studied; besides,
      separation and identification of the allelochemicals of welsh onion were also
      studied. RESULTS: Both fistular onion stalk and fistular onion leaf water
      extracts had, to different degree, inhibitory effect on the growth of M.
      aeruginosat. Compared with the control group, the fluorescence intensity of
      fistular onion stalk and fistular onion leaf were lower than the control group in
      the same period, and the inhibitory effect were more obvious with the increase of
      the water extract concentrations, to the fifth day, M. aeruginosa almost
      completely dead of the highest concentration(50 ml/L) of fistular onion stalk
      water extract treated group, the EC50 of water extract from fistular onion stalk
      to M. aeruginosa was 12.7 ml/L, equivalent to fresh weight 1.27 g/L. Main
      allelochemicals in fistular onion stalk includes allyl mercaptan, cyclopentyl
      mercaptan, and so on. The inhibiting assay on M. aeruginosa showed that the EC50
      of allyl mercaptan and cyclopentyl mercaptan respectively were 0.03 and 0.02 g/L.
      CONCLUSION: The fistular onion stalk water extracts has very good algicidal
      effect, allelopathic algal inhibiting substances primarily are sulfocompound,
      which have the potential to develop into biological algicide.

PMID- 24459916
TI  - [Research of grape seed powder on serum lipids and hepatic protection effects in
      high-fat diet rats].
AB  - OBJECTIVE: To research of grape seed powder on serum lipids and hepatic
      protection effects in high-fat diet rats. METHODS: The rats were divided into
      five groups, every group wastaken high-fat diet except control group, the
      physiological saline was administered to the control group and the high-fat diet
      groups. The doses of grape seed power in low, middle and high groups were
      determined based on the 1x , 5x , and 10x standard human doses (20 mg/60 kg BW),
      respectively. The rats were orally given test sample respectively for 28 days,
      once a day. Observed the changes of erum lipids and live pathology. RESULTS:
      Compared to the control group, the serum levels of total cholesterol (TC),
      triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) were increased
      significantly (P < 0.05) and HDL-C markedly decreased (P < 0.05) in high-fat diet
      group. The histological data with light microscopy demonstrated that the fatty
      degeneration in liver was significantly attenuated in grape seed powder rats as
      compared to high-fat diet group. CONCLUSION: The grape seed powder can reduce the
      level of serum lipids and prevent the occurrence of fatty liver.

PMID- 24459917
TI  - [Effects of resveratrol on morphology and oxidative stress of brain tissues in
      aging mice].
AB  - OBJECTIVE: To investigate the protective effects of resveratrol on brain tissues
      in aging mice induced by D-galactose. METHODS: 54 Kunming male mice aged 16 weeks
      were randomly divided into control group, aging group, intervention group. The
      control group was prepared by subcutaneous injection of normal saline and the
      other two groups were prepared by subcutaneous injection of D-galactose(200 mg/kg
      BW). The intervention group was fed with resveratrol (22.5 mg/kg BW)by oral
      gavage and the other two groups were fed with solution of 0.5% sodium
      carboxymethyl cellulose. All animals were sacrificed 16 weeks later, morphology
      of brain was observed, calculate the organ coefficients, and GSH-Px, SOD, CAT,
      MAO activity and MDA content were detected in the mice brain. RESULTS: Compared
      with the control group, the aging group lost normal morphological structure of
      nerve cells and the number of nerve cells was significantly decreased (P < 0.05),
      the organ coefficients were significantly decreased (P < 0.05), and GSH-Px, SOD,
      CAT activities were significantly decreased (P < 0.05), MAO activity and MDA
      content were significantly increased in brain of the aging group (P < 0.05).
      Compared with the aging group, the intervention group brain maintain normal
      morphological structure of nerve cells and the number of nerve cells was
      significantly increased (P < 0.05), the organ coefficients were significantly
      increased (P < 0.05), and GSH-Px, SOD, CAT activities were significantly
      increased (P < 0.05), MAO activity and MDA content were significantly decreased
      in brain of the intervention group (P < 0.05). CONCLUSION: Resveratrol can
      maintain normal morphological structure of nerve cells of aging mice, decrease
      oxidative stress responses, and has protective effects on brain tissues in aging
      mice induced by D-galactose.

PMID- 24459918
TI  - [Impacts that dimethoate inhibited the benchmark dose of acetylcholinesterase
      based on experimental designs].
AB  - OBJECTIVE: To obtain the impacts of experimental design on benchmark dose (BMD),
      and the result was applied to test the computer simulation by software Slob
      (optimal method to calculate the BMD: for a certain sample capacity, to add the
      experimental groups by reducing the amount of animals in each group) ,
      consequently, this method can be widely used in the future. METHODS: Eighty adult
      female SD rats were ig given dimethoate 0.5, 1, 2, 4, 8, 16 and 32 mg/kg for 21
      d, respectively. Rats were sacrificed, and acetylcholinesterase (AChE) activity
      in the hippocampus, cerebral cortex and serum of rats was determined after
      dimethoate was ig given to rats for 21 d. And then, the software package
      PROAST28.1 was applied to calculate the BMD. The four does groups of 10 animals
      (4 x 10 design) and 8 x 5 design were selected from 8 x 10 design to study the
      impacts of experimental design on BMD. RESULTS: Comparing with the normal
      control, the significant decline of AChE in hippocampus was observed in 2, 4, 8,
      16 and 32 mg/kg groups (P < 0.05), whereas the significant decrease was obtained
      in 0.5, 1, 2, 4, 8, 16 and 32 mg/kg groups (P < 0.05). Taking the 8 x 10 design
      as the standard, the confidence interval of BMD calculated by both of 4 x 10
      design and 8 x 5 design covered the BMD by 8 x 10 design. And also, confidence
      interval of BMD, calculated by design scheme 1, 2, 3, 4 and 6 of 4 x 10 design,
      wider than that of 8 x 5 design, but its scheme 5 narrower than 8 x 5 design.
      CONCLUSION: To add experimental groups in a certain sample capacity was the
      optimal method to calculate BMD, but was not the common toxicity experimental
      design (e. g. set four groups including control, low-dose, moderate-dose, high
      dose group).

PMID- 24459919
TI  - [Effects of fluoride on oxidative stress and apoptosis in primary culture of rat
      sertoli cells].
AB  - OBJECTIVE: To study effects of fluoride on oxidative stress and apoptosis in rat
      sertoli cells. METHODS: Intracellular reactive oxygen species (ROS) ,
      malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, mitochondrial
      membrane potential and percentage of apoptosis were measured after the rat
      sertoli cells were incubated with 0, 6, 12 and 24 microg/ml sodium fluorides or
      24 hours in vitro. RESULTS: Fluoride decreased the cell activity significantly (P
      < 0.01). The results suggested that exposure to fluoride significantly increased
      the level of ROS and MDA content (P < 0.01), fluoride also decreased SOD activity
      significantly (P < 0.05 or P < 0.01). In addition, with the NaF dose increased,
      there is a significantly decreasing in mitochondrial membrane potential and a
      significantly increasing in early apoptosis rate (P < 0.01). CONCLUSION: Fluoride
      can induce excessive oxidative stress and increased apoptosis rate in rat sertoli
      cells.

PMID- 24459920
TI  - [Inhibitory effect of microwave radiation on proliferation of human pancreatic
      cancer JF305 cells and its mechanism].
AB  - OBJECTIVE: To investigate on the proliferation effect of different intensities
      2450 MHz microwave radiation on human pancreatic cancer JF305 cells and its
      possible mechanism. METHODS: JF305 cells were radiated by intensity of 2.5, 5.0,
      10.0, 15.0 and 20.0 mW/cm2 microwave for 20 min. The proliferation capacity of
      JF305 was measured by MTT assays, Annexin V-FITC and PI staining was used for
      detecting cell apoptosis. The activity of Caspase-3 was examined. The expressions
      of Caspase-3 and HSP 70 protein after the cell treatment with microwave were
      detected by Western blotting. RESULTS: After microwave radiation, the
      proliferation inhibition rates of JF305 cells were significantly higher compared
      with control group. Annexin V-FITC and PI staining result showed that microwave
      radiation could induce cell apoptosis. Caspase-3 increased after radiated by
      microwave, compared with control group (P < 0.05). Results of Western blotting
      showed that the expression of Caspase-3 and HSP 70 protein increased
      significantly in different dosage radiation group. CONCLUSION: Microwave
      radiation can inhibit the proliferation of JF305 cells, the possible mechanism
      may be related with inducing cell apoptosis by changing of stress level.

PMID- 24459921
TI  - [Expression of p-STAT3 in laryngeal squamous carcinoma and its correlation with
      PTEN].
AB  - OBJECTIVE: To study the expression of p-STAT3 and PTEN in human laryngeal
      squamous carcinoma, to explore their relations and clinical significance. METHOD:
      Formalin-fixed and paraffin-embedded tissues from 67 cases of laryngeal squamous
      carcinoma, 25 cases of normal mucosa over 2.0 cm away from tumor margin in 25
      patients with total or subtotal laryngectomy were evaluated for the expression of
      p-STAT3, PTEN by SP immunohistochemistry, the levels of these proteins in tissues
      and their correlation with clinicopathological parameters of laryngeal squamous
      carcinoma were analyzed. The prognostic analysis was performed by Kaplan-Merier.
      RESULT: The expression rates of p-STAT3 protein in laryngeal squamous carcinoma
      and normal control laryngeal mucous tissues were 71.64%, 16% respectively. There
      was significant difference between them (Zc = 4.7052, P < 0.01); The expression
      rates of PTEN protein in laryngeal squamous carcinoma and normal control
      laryngeal mucous tissues were 41.79%, 96% respectively. There was significant
      difference between them (Zc = 5.7037, P < 0.01); The expressions of p-STAT3 and
      PTEN in laryngeal squamous carcinoma were associated with clinical stage,
      differentiation grade, lymph nodal metastases and prognosis (P < 0.01). There was
      a negative correlation between the expression of p-STAT3 and PTEN,and their
      correlation coefficient was r = -0.5148 (P < 0.01). p-STAT3 positive expression
      rate in patients survived over a 5 years follow up was 56.25% (18/32), which was
      obviously lower than the rate 82.35% (14/17) in those dead. CONCLUSION: The
      expression of p-STAT3 and PTEN may take important roles in the tumorigenesis,
      aggressiveness, metastases and prognosis of laryngeal squamous carcinoma. The
      high expression of p-STAT3 was negatively correlated with the lower PTEN in
      laryngeal squamous carcinoma, which suggested that PTEN may be a downstream
      target gene of p-STAT3.

PMID- 24459923
TI  - [Treatment of cervical esophageal perforation].
AB  - OBJECTIVE: To investigate the repair of cervical esophageal perforation using
      cervical muscle flap and provide a new material of esophageal perforation repair.
      METHOD: To report 12 cases of cervical esophageal perforation among which 8 cases
      was repaired using cervical muscle flap. RESULT: 100% success rate of surgical
      repair was observed with all 12 cases. No case of recurrence or esophageal
      stricture occurred by follow-up six months to 10 years. CONCLUSION: Traumatic
      cervical esophageal perforation easily had serious complications, with high
      mortality rates and the prognosis was poor. Early intervention of surgical repair
      could improve the survival rate of patients.

PMID- 24459922
TI  - [Expression and significance of hMSH2 protein in laryngeal squamous cell
      carcinoma].
AB  - OBJECTIVE: To study the expression and significance of hMSH2 protein in laryngeal
      squamous cell carcinoma. METHOD: The expression of hMSH2 protein were detected by
      immunohistochemistry SP method in 51 cases of laryngeal squamous cell carcinoma,
      the control group included 30 cases of atypical hyperplasia tissue of vocal fold
      and 16 cases of normal laryngeal tissue. RESULT: The expression rates of hMSH2 in
      laryngeal squamous cell carcinoma, atypical hyperplasia tissue of vocal fold and
      normal laryngeal tissue were 58.8%, 73.3%, 87.5% respectively. There was
      significant difference among them (P < 0. 05). The expression of hMSH2 in
      laryngeal carcinoma was not associated with location and T stage (P > 0.05), but
      the expression was related with metastasis of lymph node and differentiation
      level (P < 0.05). CONCLUSION: The deletion of hMSH2 maybe participate the early
      occurrence of laryngeal carcinoma; hMSH2 protein maybe delay and suppress
      oncogenesis and development of laryngeal carcinoma.

PMID- 24459924
TI  - [Expression and significance of phosphated signal transducer and activator of
      transcription 3 and p53 protein in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expression and clinical significance of phosphated
      signal transducer and activator of transcription 3 (p-STAT3) and p53 protein in
      laryngeal squamous cell carcinoma (LSCC), and the relationship between the two
      genes. METHOD: Formalin-fixed and paraffin-embedded tissues, which came from 60
      cases of LSCC and 32 samples of normal mucosa over 2.0 cm away from tumor margin
      in 32 patients with total or subtotal laryngectomy were detected for the
      expression of p-STAT3 and p53 protein by in SP immunohistochemistry. Micro-image
      analysis system was used to determine the optical density,and the result was
      analyzed statistically. RESULT: There is over expression of p-STAT3 and p53
      protein in LSCC. The expression of p-STAT3 and p53 protein in LSCC was associated
      with clinical stage and lymph nodal metastases (P < 0.05). There was a positive
      correlation between the expression of p-STAT3 and P53 protein. The correlation
      coefficient (r) was 0.6558 (P < 0.01). CONCLUSION: The expression of p-STAT3 and
      p53 protein may play an important role in the tumorigenesis,metastases and poor
      prognosis of LSCC. There was a positive correlation between the over expression
      of p-STAT3 and p53 protein in LSCC.

PMID- 24459925
TI  - [Meta-analysis on the risk factors for stomal recurrence after total
      laryngectomy].
AB  - OBJECTIVE: To evaluate the risk factors of stomal recurrence in patients after
      total laryngectomy. METHOD: A thorough literature search was performed among
      Wanfang database, Chinese Scientific Journals Database of VIP and pubmed
      database. Meta analysis was performed on a total of 2725 patients in 2 Chinese
      papers and 6 English papers which met the inclusion criteria. Data was analyzed
      by RevMan 5.0 software. RESULT: Subglottic and transglottic location (tumor
      location), the extent of the tumor of the primary site (T4), preoperative
      tracheotomy were important risk factors of recurrence after total laryngectomy.
      CONCLUSION: Subglottic and transglottic location (tumor location), the extent of
      the tumor of the primary site (T4), preoperative tracheotomy were related to
      stomal recurrence after total laryngectomy.

PMID- 24459926
TI  - [Four cases of extraskeletal Ewing's sarcoma in the head and neck and literature
      review].
AB  - OBJECTIVE: To evaluate the clinical features,diagnosis,treatment and prognosis of
      the extraskeletal Ewing's sarcoma in the head and neck. METHOD: The clinical data
      of four cases of extraskeletal Ewing's sarcoma was analysed and relevant
      literatures were reviewed. RESULT: Two cases originated from the nasal cavity and
      paranasal sinuses, the other two cases originated from the oral pharynx and skin
      respectively. The tumors were all diagnosed via histopathology and
      immunohistochemistry. Two cases were treated by combined modality therapy and did
      not recur or metastasize after follow-up for 7 months and 7 years respectively.
      Another one was treated by surgery and died after 6 months of follow-up. The
      remaining one was treated by chemotherapy and died with metastasis during the
      period of therapy. CONCLUSION: The extraskeletal Ewing's sarcoma, which is rare
      arising from the head and neck, has non-specific clinical manifestation and
      difficulty in early diagnosis. The disease can be effectively treated by combined
      therapy, but the high recurrent and metastatic rates usually result in poor
      prognosis.

PMID- 24459927
TI  - [Analysis and management of postoperative hemorrhage in surgery of obstructive
      sleep apnea hypopnea syndrome in children using plasma-mediated radio-frequency
      ablation at low temperature].
AB  - OBJECTIVE: To analyze retrospectively cause, prevention and management of
      postoperative hemorrhage in surgery of obstructive sleep apnea hypopnea syndrome
      (OSAHS) in children using plasma-mediated radio-frequency (pmRF) ablation at low
      temperature. METHOD: Tonsil and adenoid ablation were carried out in 4028 cases
      diagnosed with OSAHS, using ENTColator lI plasma system of Arthocare company
      under general anesthesia. RESULT: Postoperative hemorrhage occurred in 37 cases
      of 4028 cases, among which 1 case occurred after tonsil ablation and other 36
      cases occurred after adenoid ablation. Primary hemorrhage was in 7 cases, while
      secondary hemorrhage in other 30 cases. Cessation of bleeding was achieved by
      using different methods of hemostasis in all cases. CONCLUSION: Tonsil and
      adenoid ablation were performed by pmRF at low temperature with advantages of
      less trauma, less bleeding. However, postoperative hemorrhage might occur in a
      few cases (accounting for 0.92%). Postoperative hemorrhage in these patients was
      related with preoperatively incomplete control of inflammation of tonsil or
      adenoid, surgeon's experience, intraoperatively incomplete hemostasis,
      postoperative crying and restlessness, eating improperly in two weeks after
      surgery, coagulation factor deficiency. In case of postoperative hemorrhage, good
      outcome could be achieved by management of compression, pmRF at low temperature,
      bipolar coagulation.

PMID- 24459928
TI  - [Clinical analysis of 20 patients with primary non-Hodgkin's lymphoma of nasal
      cavity and nasopharynx].
AB  - OBJECTIVE: To evaluate the treatment policy for non-Hodgkin's lymphoma of the
      nasal cavity and nasopharynx. METHOD: Twenty patients with pathologically
      confirmed non-Hodgkin's lymphoma of nasal cavity and nasopharynx,treated from
      Jan. 2006 to Oct. 2010, were retrospectively reviewed. RESULT: The 3-year overall
      survival and complete response rates for all patients were 78% and 47%
      respectively. The 3-year overall survival rates for patients treated with
      chemotherapy and patients treated with chemotherapy plus radiotherapy were 75%
      and 82% respectively. The estimates of complete response for patients receiving
      chemotherapy alone and for patients receiving chemotherapy plus radiotherapy were
      37% and 55%, respectively. The 3-year overall survival rates for patients who
      achieved complete response and patients who did not were 89% and 70%,
      respectively. The 3-year overall survival rates for patients in stage IE and
      stage II E were 92% and 57%, respectively. CONCLUSION: There was no significant
      difference between chemotherapy alone and chemotherapy plus radiotherapy for the
      treatment of non-Hodgkin's lymphoma of the nasal cavity and nasopharynx. The 3
      year overall survival rate for patients in stage IE was much higher than in stage
      II E. Early treatment is very important to improve the survival rate of the
      patients.

PMID- 24459929
TI  - [Endovascular treatment of the pseudoaneurysms of extracranial segment of
      internal carotid artery].
AB  - OBJECTIVE: To discuss the endovascular interventional treatment of pseudoaneurysm
      of extracranial segment of internal carotid artery. METHOD: The clinical data of
      5 cases with traumatic pseudoaneurysm of extracranial segment of internal carotid
      artery were retrospectively studied. RESULT: All the patients were cured via
      endovascular interventional treatment, and performed with implanting covered
      stent into the parent artery. The patients recovered well with patency of the
      parent artery. CONCLUSION: Endovascular interventional treatment with covered
      stent implantation was safe and effective in treatment of pseudoaneurysm of
      extracranial segment of internal carotid artery.

PMID- 24459930
TI  - [Changes of serum leptin levels in patients with obstructive sleep apnea-hypopnea
      syndrome before and after treatment of surgery].
AB  - OBJECTIVE: To investigate the change of serum leptin levels in patients with
      obstructive sleep apnea hypopnea syndrome (OSAHS) before and after surgery.
      METHOD: The cases were divided into effective (n=44) and non-effective (n=13)
      groups according to PSG. The effective cases were divided into decreased (> or =
      5%, n=25) and non-decreased(<5%, n=19) BMI. The level of serum leptin was
      detected by radioimmunoassay. RESULT: The level of serum leptin after treatment
      (9.1 +/- 2.6 microg/L) was as high as before treatment (9.3 +/- 2.3 microg/L) in
      13 non-effective cases. The level of serum leptin after treatment (7.15 +/- 1.23
      microg/L) was significantly decreased than before treatment (12.79 +/- 2.98
      microg/L) in 25 cases of decreased BMI (> or = 5%). The level of serum leptin
      after treatment (7.15 +/- 1.23 microg/L) was significantly decreased than before
      treatment (12.79 +/- 2.98 microg/L) in 19 cases of non-decreased BMI (<5%).
      Leptin level of all cases showed a positive correlation with AHI (P < 0.01).
      CONCLUSION: The level of serum leptin in patients with OSAHS are increased. The
      serum leptin level of effective patients with OSAHS after treatment was
      significantly decreased. The level of serum leptin reflects the degree of AHI in
      patients with OSAHS.

PMID- 24459931
TI  - [The difference of phonation patterns in vocal fold polyps and vocal nodules].
AB  - OBJECTIVE: To investigate the difference of phonation patterns by dividing
      patients with vocal fold polyps and vocal nodules into two groups according to
      muscle tension patterns (MTP). METHOD: Fifty-six patients with vocal fold polyps
      and vocal nodules were divided into two groups according to phonation with MTP or
      not by video strobolaryngoscopy. RESULT: MTP could be found in 85% patients with
      vocal nodules and in 55.56% patients with vocal fold polyps. Significant
      difference was found in patients with/without MTP, and difference was also found
      in every type of MTP. CONCLUSION: MTP lies in most patients with vocal nodules
      while only part of patients with vocal fold polyps, which indicated that vocal
      fold polyps and vocal nodules may demonstrate different phona

PMID- 24459932
TI  - [The clinical significance of synchronous monitoring with micro-movement
      sensitive mattress sleep monitoring system and apnea graph].
AB  - OBJECTIVE: To investigate the relevance and clinical value of synchronous
      monitoring with Apnea Graph (AG) and micro movement sensitive mattress sleep
      monitoring system (MSMSMS) for the patient with obstructive sleep apnea-hypopnea
      syndrome before surgery. METHOD: One hundred and fifteen patients diagnosed as
      OSAHS by PSG were synchronous examined by two methods: MSMSMS and AG with
      continuous upper airway pressure recording at night in Peking Union Medical
      College Hospital. The apnoeic and oxygen desaturation events during sleep
      determined by the two methods were compared. The correlation between MSMSMS and
      AG were analyzed. RESULT: According to the OSAHS severity grading: the mild,
      moderate and severe were 6, 16, 93 for AG and 8, 26, 81 for MSMSMS respectively,
      and the hypoxemia severity grading:the mild, moderate, severe were 14, 70, 27 for
      AG and 6, 72, 37 for MSMSMS respectively. There were no statistically difference
      in the severity grading of OSAHS and hypoxemia during sleep determined by AG and
      MSMSMS. According to the parameters of the two methods, the AHI are (51.5 +/-
      21.2) times/h (x +/- s, similarly hereinafter) and (48.1 +/- 24.2) times/h, r =
      0.947; the LSaO2 are 0.736 +/- 0.110 and 0.710 +/- 0.108, r = 0.935; the
      correlation coefficient (r) of apnea index and obstructive apnea and hypopnea
      index were 0.856 and 0.841, P < 0.01 respectively, the data monitored by the two
      methods is positively correlated. CONCLUSION: There is no significant difference
      in determining the severity of OS AHS between the AG and MSMSMS. The two methods
      had good correlation in respiratory disturbance index and oxygen decline index,
      and revealed well-prospects of preoperative assessment in patients with OSAHS.

PMID- 24459933
TI  - [Clinical application of ultracision-harmonic scalpel in parotid gland surgery].

PMID- 24459934
TI  - [Experiences and lessons of application of submental island flap].

PMID- 24459935
TI  - [The acoustic comparison of different voice rehabilitation after total
      laryngectomy].

PMID- 24459936
TI  - [Analysis on diagnosis and treatment of special type of sublingual cyst].

PMID- 24459937
TI  - [One case of elderly patients with bronchial foreign body].
AB  - This paper reports one case of elderly patients with bronchial foreign body, and
      analyzes the causes of misdiagnosis. And the best choice of removing larger
      foreign body is operating under rigid bronchoscopy.

PMID- 24459938
TI  - [A childhood nasopharyngeal carcinoma with huge mass in skull base].
AB  - The patient chiefly complained about headache and facial pain with recurrent
      epistaxis during the past two months. The pain started from the teeth and
      intermittent pinching headache especially on the left side. She also had mild
      epistaxis which healed itself. Later on the epistaxis became severe which
      couldn't be easily cured. Her nasopharyngoscopy examination showed a mass in
      nasopharynx while cranial CT scan indicated a huge mass in nasopharynx with
      erosion of skull base. Enhanced CT scan showed significant thickness in
      nasopharynx, upwards which became a huge mass breaking through skull base
      especially on the left side. Adjacent parapharyngeal space and paranasal sinuses
      and skull base were widely involved with the enlargement of neck lymph nodes. The
      chronic mastoiditis, ethmoiditis and maxillary sinusitis were also found.
      DIAGNOSIS: nasopharyngeal nonkeratinizing squamous cell carcinoma (T4N2M0 stage
      IV).

PMID- 24459939
TI  - [Inflammatory myofibroblastic tumor of the larynx in a 9-year-old boy].
AB  - This 9-year-old boy presented with dysphonia and dyspnea for one month.
      Laryngoscopy showed a tumor of anterior vocal cord. The patient received a
      tumorectomy, immunohistochemistry concluded to the diagnosis of inflammatory
      myofibroblastic tumor.

PMID- 24459940
TI  - [The role and mechanism of anticancer of dihydroartemisinin].
AB  - Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has
      recently shown antitumor activity in various cancer cells including cancers of
      cervix, pancreas, prostate, liver and neuroblastoma. Numerous studies in vivo and
      in vitro indicate that DHA possesses unique antitumor features and appears to be
      a promising chemotherapeutic agents. Here we systematically review the advances
      in research of anticancer of dihydroartemisinin, as well as summarize the
      mechanisms of its inducing apoptosis,delay cell-cycle, inhibitory cell
      proliferation and downregulate angiogenesis.

PMID- 24459941
TI  - [Progress of positive airway pressure and upper airway multilevel surgeries in
      the treatment of obstructive sleep apnea-hypopnea syndrome].
AB  - This review focus on the progress of the treatment of obstructive sleep apnea
      hypopnea syndrome by using positive airway pressure and upper airway multilevel
      surgeries. OSAHS is a disease caused by multiple etiologies. We should consider
      upper airway anatomical abnormalities and the severity of OSAHS before reasonable
      treatment plans were formulated. "PAP-surgery-PAP" is the classic procedure for
      treating moderate OSAHS and severe OSAHS. Preoperative use of PAP could reduce
      the hypoxic condition of patients and decrease surgical risk. Surgery can
      effectively reduce the optimal PAP pressure value, and increase the tolerance of
      patient. Postoperative use of PAP can improve surgical efficacy, shorten patient
      recovery time. However, the influence of different surgical methods on optimal
      PAP pressure value is lacking in large samples. More related studies need to be
      per formed in the future.

PMID- 24459942
TI  - [A leukocyte pattern recognition based on feature fusion in multi-color space].
AB  - To solve the ineffective problem of leukocytes classification based on multi
      feature fusion in a single color space, we proposed an automatic leukocyte
      pattern recognition by means of feature fusion with color histogram and texture
      granular in multi-color space. The interactive performance of three color spaces
      (RGB, HSV and Lab), two features (color histogram and texture granular) and four
      similarity measured distance metrics (normalized intersection, Euclidean
      distance, chi2-metric distance and Mahalanobis distance) were discussed. The
      optimized classification modes of high precision, extensive universality and low
      cost to different leukocyte types were obtained respectively, and then the
      recognition system of tree-integration of the optimized modes was established.
      The experimental results proved that the performance of the fusion classification
      was improved by 12.3% at least.

PMID- 24459943
TI  - [Identification of gastric cancer-related differentially expressed genes by
      combining PCA and ICA].
AB  - Screening potential differentially expressed genes can help us to understand the
      functions of the genes and their roles in disease development. Due to the
      different emphases of the principal component analysis and independent component
      analysis, a novel method that combines principal component analysis and
      independent component analysis is proposed to identify differentially expressed
      genes associated with gastric cancer for the improvement of accuracy and
      credibility of results. This method screens out 16 differentially expressed genes
      which is significantly related to the occurrence and development of gastric
      cancer from gastric cancer gene expression data with 7129 genes and 29 samples.
      These genes are worthy to be studied experimentally. The results of this paper
      are helpful for revealing the occurrence and development mechanism of gastric
      cancer.

PMID- 24459944
TI  - [The recognition methodology study of epileptic EEGs based on support vector
      machine].
AB  - EEG recordings contain valuable physiological and pathological information in the
      process of seizure. The dynamic changes of brain electrical activity provide
      foundation and possibility for research and development of automatic detection
      system about epilepsy. In this paper, a nonlinear dynamic method is presented for
      analysis of the nonlinear dynamic characteristics of EEGs and delta, theta,
      alpha, and beta sub-bands of EEGs based on wavelet transform. The extracted
      feature is used as the input vector of a support vector machine (SVM) to
      construct classifiers. The results showed that the classification accuracy of SVM
      classifier based on nonlinear dynamic characteristics to classify the EEG into
      interictal EEGs and ictal EEGs reached 90% or higher. The support vector machine
      has good generalization in detecting the epilepsy EEG signals as a nonlinear
      classifier.

PMID- 24459945
TI  - [Research on tumor information grid framework].
AB  - In order to realize tumor disease information sharing and unified management, we
      utilized grid technology to make the data and software resources which
      distributed in various medical institutions for effective integration so that we
      could make the heterogeneous resources consistent and interoperable in both
      semantics and syntax aspects. This article describes the tumor grid framework,
      the type of the service being packaged in Web Service Description Language (WSDL)
      and extensible markup language schemas definition (XSD), the client use the
      serialized document to operate the distributed resources. The service objects
      could be built by Unified Modeling Language (UML) as middle ware to create
      application programming interface. All of the grid resources are registered in
      the index and released in the form of Web Services based on Web Services Resource
      Framework (WSRF). Using the system we can build a multi-center, large sample and
      networking tumor disease resource sharing framework to improve the level of
      development in medical scientific research institutions and the patient's quality
      of life.

PMID- 24459946
TI  - [A novel denoising approach to SVD filtering based on DCT and PCA in CT image].
AB  - Because of various effects of the imaging mechanism, noises are inevitably
      introduced in medical CT imaging process. Noises in the images will greatly
      degrade the quality of images and bring difficulties to clinical diagnosis. This
      paper presents a new method to improve singular value decomposition (SVD)
      filtering performance in CT image. Filter based on SVD can effectively analyze
      characteristics of the image in horizontal (and/or vertical) directions.
      According to the features of CT image, we can make use of discrete cosine
      transform (DCT) to extract the region of interest and to shield uninterested
      region so as to realize the extraction of structure characteristics of the image.
      Then we transformed SVD to the image after DCT, constructing weighting function
      for image reconstruction adaptively weighted. The algorithm for the novel
      denoising approach in this paper was applied in CT image denoising, and the
      experimental results showed that the new method could effectively improve the
      performance of SVD filtering.

PMID- 24459947
TI  - [Molecular simulation research on aggregation of insulin].
AB  - In the present research, molecular simulation and quantum chemistry calculations
      were combined to investigate the thermal stability of three kinds of insulin
      aggregations and the effect of Zn (II) ion coordination on these aggregations.
      The results of molecular simulation indicated that the three insulin dimers in
      the same sphere closed hexamer had synergistic stability. It is the synergistic
      stability that enhances the structural and thermal stability of insulin,
      preserves its bioactivity during production, storage, and delivery of insulin
      formulations, and prolongs its halflife in human bodies. According to the results
      of quantum chemistry calculations, each Zn (II)-N (Im-insulin) bond energy can
      reach 73.610 kJ/mol for insulin hexamer and 79.907 kJ/mol for insulin tetramer.
      However, the results of Gibbs free energy changes still indicats that the
      coordination of zinc (II) ions is unfavorable for the formation of insulin
      hexamer, because the standard Gibbs free energy change of the coordinate reaction
      of zinc (II) ions associated with the formatting insulin hexamer is positive and
      increased.

PMID- 24459948
TI  - [The comparison of algorithms on the CT image retrieval of Xinjiang local liver
      hydatid disease].
AB  - Xinjiang local liver hydatid disease is an infectious parasitic disease in
      Xinjiang pastoral areas. Based on the image features, selecting the appropriate
      distance algorithms to retrieve the image quickly and accurately, different
      distance algorithms have been induced in this area, which can greatly assist the
      doctors to early detect, diagnose and cure the liver hydatid disease. This paper
      compared the performance of different distance algorithms to retrieve the image
      when using the liver hydatid disease medical image texture features. The results
      showed that: for the liver hydatid disease medical images retrieval based on gray
      level cocurrence matrix (GLCM) texture features, the Mahalanobis distance
      algorithm is superior to other distance algorithms.

PMID- 24459949
TI  - [A systematic evaluation of application of the web-based cancer database].
AB  - In order to support the theory and practice of the web-based cancer database
      development in China, we applied a systematic evaluation to assess the
      development condition of the web-based cancer databases at home and abroad. We
      performed computer-based retrieval of the Ovid-MEDLINE, Springerlink, EBSCOhost,
      Wiley Online Library and CNKI databases, the papers of which were published
      between Jan. 1995 and Dec. 2011, and retrieved the references of these papers by
      hand. We selected qualified papers according to the pre-established inclusion and
      exclusion criteria, and carried out information extraction and analysis of the
      papers. Eventually, searching the online database, we obtained 1244 papers, and
      checking the reference lists, we found other 19 articles. Thirty-one articles met
      the inclusion and exclusion criteria and we extracted the proofs and assessed
      them. Analyzing these evidences showed that the U.S.A. counted for 26% in the
      first place. Thirty-nine percent of these web-based cancer databases are
      comprehensive cancer databases. As for single cancer databases, breast cancer and
      prostatic cancer are on the top, both counting for 10% respectively. Thirty-two
      percent of the cancer database are associated with cancer gene information. For
      the technical applications, MySQL and PHP applied most widely, nearly 23% each.

PMID- 24459950
TI  - [Study of decision tree in the application of predicting protein-protein
      interactions].
AB  - Proteins are the final executive actor of cell viability and function. Protein
      protein interactions determine the complexity of the organism. Research on the
      protein interactions can help us understand the function of the protein at the
      molecular level, learn the cell growth, development, differentiation, apoptosis
      and understand biological regulation mechanisms and other activities. They are
      essential for understanding the pathologies of diseases and helpful in the
      prevention and treatment of diseases, as well as in the development of new drugs.
      In this paper, we employ the single decision-tree classification model to predict
      protein-protein interactions in the yeast. The original data came from the
      existing literature. Using software Clementine, this paper analyzes how these
      attributes affect the accuracy of the model by adjusting the predicted
      attributes. The result shows that a single decision tree is a good classification
      model and it has higher accuracy compared to those in the previous researches.

PMID- 24459951
TI  - [Wave information system design of radial artery pulse in the hemodialyst].
AB  - In the process of hemodialysis, the patients' blood pressure and pulse wave are
      likely to change considerably so that hypotension and rapid heart rate may be
      dangerous to the hemodialysts' life. Based on the environment of hemodialysis
      room, we designed the communication system using SPCE061A single-chip computer
      and STC89C52 single-chip computer to realize wireless communication between upper
      system and the two single-chip computers, and on the upper computer the pulse
      wave can display at real-time and save data on the data base. At the same time we
      designed an interface program to reduce noise by way of frequency domain analysis
      and wavelet denoising. It can draw the cycle pulse wave, eigenvalue-K, the
      maximum peak and peak frequency, it can effectively judge a racing heart in the
      hemodialysis and can also evaluate vascular sclerosis of hemodialysis. In short,
      the system is able to improve treatment security and reduce the burden of the
      doctors and nurses in hemodialysis rooms.

PMID- 24459952
TI  - [Research of the glomerular filtration rate estimation model].
AB  - The glomerular filtration rate (GFR) is an important index of renal function with
      advantages of accurate, sensitive, stable, repetitive and accurate measurement of
      renal functions. The GFR is mainly determined in the clear rate of radioisotope
      markers (99m)Tc-DTPA, the process of which is complicated, long time-taking, high
      cost, and radioactively injuring. Recently, the methods using other renal
      function parameters measured easily to create the mathematic models and to
      estimate GFR are being investigated in the world. In this paper, for the renal
      function data of the Chinese, the efficiency in the three existing GFR formulas
      has been optimized with multi-function optimization techniques and the accuracy
      of the computation has been improved. Then the BP neural network technology is
      used for establishing a new GFR formula, which is a simpler form and obtains
      higher precision result than the formulas existed. The rmse and P30 of the new
      formula are better than those of the old ones.

PMID- 24459953
TI  - [Preliminary establishment of an electrochemiluminescence immunoassay method for
      detection of influenza virus B].
AB  - To establish an electrochemiluminescence immunoassay (ECLIA) for the detection of
      influenza virus B (Flu B), we biotinylated the Flu B monoclonal antibody
      (mAb),labeled the paired Ab with ruthenium and used the streptavidin-coated
      microparticles in this study. The ECL intensity was linear with the
      concentrations of antigen of Flu B in the range of 0.55 microg/mL to 17.5
      microg/mL, with a detection limit of 0.55 microg/mL (S/N= 3). The
      precision,sensitivity and specificity were evaluated. The established ECLIA for
      Flu B antigen in this study was specific, sensitive and precise. It may provide a
      convenient and rapid technique for clinical detection of Flu B.

PMID- 24459954
TI  - [Analysis of EEG in the elderly with mild cognitive impairment based on Lempel
      Ziv complexity].
AB  - We studied the mechanism of electroencephalography (EEG) in the elderly with mild
      cognitive impairment (MCI) by analyzing the Lempel-Ziv complexity (LZC) of EEG
      during a cognitive task. We recorded the EEG simultaneously when they were asked
      to judge whether the color of two graphics was matched or not. The results showed
      that the LZC of EEG in the MCI group was significantly higher than those in the
      normal control group early in the period of cognitive activities (P < 0.05). The
      LZC in MCI patients decreased gradually over time, while results of the normal
      group kept unchanged. There was no significant difference in LZC between two
      types of tasks. The two groups showed similar regularity in spatial distribution.

PMID- 24459955
TI  - [Biometric identification method for ECG based on the piecewise linear
      representation (PLR) and dynamic time warping (DTW)].
AB  - To treat the problem of identification performance and the complexity of the
      algorithm, we proposed a piecewise linear representation and dynamic time warping
      (PLR-DTW) method for ECG biometric identification. Firstly we detected R peaks to
      get the heartbeats after denoising preprocessing. Then we used the PLR method to
      keep important information of an ECG signal segment while reducing the data
      dimension at the same time. The improved DTW method was used for similarity
      measurements between the test data and the templates. The performance evaluation
      was carried out on the two ECG databases: PTB and MIT-BIH. The analystic results
      showed that compared to the discrete wavelet transform method, the proposed PLR
      DTW method achieved a higher accuracy rate which is nearly 8% of rising, and
      saved about 30% operation time, and this demonstrated that the proposed method
      could provide a better performance.

PMID- 24459956
TI  - [Comparison of collateral circulation characteristics between Budd-Chiari
      syndrome and hepatitis B related liver cirrhosis with CT angiography].
AB  - This study was aimed to investigate the imaging features of collateral
      circulation in Budd-Chiari syndrome (BCS) and hepatitis B related liver cirrhosis
      (LC) with multi-detector computed tomography (MDCT), and to discuss the value of
      MDCT in differential diagnosis of Budd-Chiari syndrome and hepatitis B related
      LC. Sixty cases of LC confirmed by medical history and laboratory examination and
      15 cases of BCS proven by histopathology or ultrasonography were recruited in the
      present study. Morphological changes and anatomic characteristics were assessed
      with three dimensional (3D) vascular reconstruction of MDCT in all 75 cases.
      There were significantly more subjects with caudate lobe enlargement in BCS (11
      cases, 73%) than in LC (5 cases, 8%). In BCS group, extrahepatic collateral
      circulation of ascending lumbar and azygous collateral pathways were found in 9
      cases and epigastric varicose veins in 8 cases. Intrahepatic venous collaterals
      were documented in 12 cases combined with ascending lumbar and azygous vein
      collaterals in 9 cases and retroperitoneal varicose vein plexus in 6 cases. These
      intra- and extra-hepatic venous collaterals were not dectected in patients with
      LC. Morphological changes of the caudate lobe and the enhanced pattern of liver
      parenchyma were significantly different between patients with BCS and LC. Thus,
      it could be well concluded that contrast-enhanced CT scan and 3D CT angiography
      are very useful in differential diagnosis of BCS and LC.

PMID- 24459957
TI  - [Rapid identification of QRS wave based on the moving window].
AB  - A fast and accurate intelligent identification is the developing trend of
      electrocardiogram (ECG) research. However, there are few methods by which
      satisfactory results could be obtained both in speed and in accuracy. A fast
      identification method of QRS wave was proposed based on moving window operation
      in this study. An 80 ms wide moving window was employed, in which simple
      difference and product operations were carried out with simple and less
      computation, and a very good inhibition of P and T waves and other noises was
      realized. Then the method was investigated with data from the MIT-BIH arrhythmia
      database with absence of digital filtering de-noising, and the identification
      accuracy of QRS complex reached 99.6%. The results showed that a rapid and
      accurate identification of QRS complex could be realized, which would meet the
      requirements for studying the real-time ECG monitoring equipment.

PMID- 24459958
TI  - [Comparative analysis of dual resource computed tomography angiography and 3.0T
      magnetic resonance angiography in the diagnosis of intracranial aneurysms].
AB  - To comparatively study the diagnostic value of dual resource computed tomography
      angiography (DSCTA) and 3.0T magnetic resonance angiography (MRA) for
      intracranial aneurysm, we analyzed retrospectively radiographic data of DSCTA,
      3.0T MRI and three dimensional digital subtraction angiography (3D DSA ) in cases
      suspected intracranial aneurysms during Jan. 2010 to Dec. 2011. With 3D DSA as
      "gold standard", the sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of DSCTA and 3.0T MRA in diagnostic of
      intracranial aneurysms were analyzed, and the accuracy of both methods on
      evaluation of aneurysms size was compared as well. Totally fifty-three suspected
      cases were included, and forty-two intracranial aneurysms in thirty-five cases
      were identified by 3D DSA. For DSCTA, 37 aneurysms were detected in 32 patients,
      and 3 patients and 5 aneurysms were missed in all patients. However, for 3.0 T
      MRA, 33 aneurysms were detected in 33 patients, 5 patients and 8 aneurysms were
      missed, and 3 patients who did not have aneurysms were misdiagnosed as ones with
      intracranial aneurysms. The sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of DSCTA and 3.0T MRA were 91.4% vs.
      85.7%, 100% vs. 83.3%, 100% vs. 90.9%, 85.7% vs. 75.0% and 94.3% vs.
      84.9%,respectively. There was no significant difference in evaluation of
      aneurysms size between using the two methods. Data suggested that both DSCTA and
      3.0T MRA had high accuracy for detection intracranial aneurysms and evaluation of
      aneurysms size, but as for detection of microaneurysms, DSCTA was superior to
      3.0T MRA.

PMID- 24459959
TI  - [An algorithm based on ECG signal for sleep apnea syndrome detection].
AB  - The diagnosis of sleep apnea syndrome (SAS) has a significant importance in
      clinic for preventing diseases of hypertention, coronary heart disease,
      arrhythmia and cerebrovascular disorder, etc. This study presents a novel method
      for SAS detection based on single-channel electrocardiogram (ECG) signal. The
      method preprocessed ECG and detected QRS waves to get RR signal and ECG-derived
      respiratory (EDR) signal. Then 40 time- and spectral-domain features were
      extracted to normalize the signals. After that support vector machine (SVM) was
      used to classify the signals as "apnea" or "normal". Finally, the performance of
      the method was evaluated by the MIT-BIH Apnea-ECG database, and an accuracy of
      95% in train sets and an accuracy of 88% in test sets were achieved.

PMID- 24459960
TI  - [Diagnostic value of left ventricular function after adenosine loading detected
      by gated myocardial perfusion imaging for prediction of major adverse cardiac
      events].
AB  - This study was aimed to analyze the value of the SPECT MPI to myocardial ischemia
      and cardiac function parameters in the CAD prognosis assessment. A total of 890
      patients with suspected CAD underwent adenosine loading stress gated SPECT. At a
      mean follow-up of (2.3 +/- 0. 4) year, a total of 37 adverse events occurred,
      including 12 cardiac deaths and 25 nonfatal myocardial infarctions. Univariate
      Cox analysis showed that diabetes (wald 6.95, P < 0.01), SSS (wald 24.31, P <
      0.001), EF (wald 17.14, P < 0.001), ESV (wald 8.58, P < 0.01) and EDV (wald 7.95,
      P < 0.01) were significant predictors of MACEs. Multivariate Cox analysis showed
      that SSS (wald 6.69, P < 0.05) and EF (wald 4.70, P < 0.05) were independent
      predictors. According to the results, SSS and EF are both independent predictors
      of MACEs.

PMID- 24459961
TI  - [Evaluation of the importance of herbs in the Chinese herbal compounds based on
      the theory of rough sets].
AB  - The theory of rough sets has been applied to evaluate the importance of each herb
      in the Chinese herbal compounds in this study. This method could distinguish core
      herbs through different syndrome types in the same class of prescription by
      measuring the importance of attributes. Compared to the frequency statistical
      method, the rough sets method could reveal law of compatibility in categorized
      formula more deeply. This study gives some guidance to clinical application of
      herbs and the drug screening in the development of new Chinese traditional
      medicine.

PMID- 24459962
TI  - [Investigation on disturbing of adipocytic differentiation of rBMSCs by loaded
      titanium particles].
AB  - Our previous investigations demonstrated that varying sizes of loaded titanium
      particles could inhibit proliferaion, adhension and osteoblastic differentiation
      of rat bone marrow mesenchymal stem cells (rBMSCs). The present study aims to
      validate the hypothesis that particled-shaped wear debris from prosthetic
      implants influence the adipocytic differentiation of rBMSCs. The effects of
      different sizes of loaded titanium particles (6.9 microm, 2.7 microm and 0.9
      microm) on the adipocytic differentiation of rBMSCs were studied by observing
      lipid droplet formation, assaying the expression of lipoprotein lipase (LPL) mRNA
      by RT-PCR and Triglycerides (TG) secretion. The loaded titanium particles were
      found to influence adipogenesis of rBMSCs, but had different effects, depending
      upon particle size, concentration and loading time duration. 2.7 microm and 0.9
      microm titanium particles promoted lipid droplet formation, LPL mRNA expression
      and TG secretion, while at a higher concentration of titanium particles and a
      longer loading duration, 6.9 microm titanium particles gradually inhibited
      adipogenic differentiation of rBMSCs. Three sizes of loading titanium particles
      obviously disturbed the adipocytic differentiation capability of rBMSCs: the
      smaller particles promoted but the larger inhibited the adipogenic
      differentiation of rBMSCs.

PMID- 24459963
TI  - [Characterization of collagen/polyvinyl alcohol complex membrane crosslinked by
      UV-riboflavin].
AB  - The objective of this investigation was to study the characteristics and
      biocompatibility of collagen/polyvinyl alcohol (PVA) membrane crosslinked by UV
      riboflavin. Membranes that were made into complex ones with different mass ratios
      of collagen to PVA (1:1 and 2:1) were synthesized, and crosslinked with UV
      riboflavin. The surface characteristics were analyzed using the omnipotent
      materials instrument, IR, SEM, water absorption test, gas permeability test, and
      degradation test, respectively. The biocompatibility of membrane complex and rat
      bone marrow mesenchymal stem cells (BMSCs) was evaluated after 7 d and 14 d,
      respectively. The collagen/PVA complex membranes showed good homogeneity,
      mechanical property, degradation ratio, water absorption, gas permeability, etc.
      The biocompatibility of the collagen/PVA (2:1) complex membrane crosslinked with
      UV-Riboflavin was higher than that of without crosslinking and collagen/PVA (1:1)
      membrane. It could be well concluded that collagen/PVA complex membranes
      crosslinked with UV-riboflavin would have a potential application in biomedicine.

PMID- 24459964
TI  - [Effect of titanium particles and TNF-alpha on the gene expression and activity
      of MMP-1, 2, 3 in human knee joint synovial cells].
AB  - This paper is aimed to investigate the effect of titanium (Ti) particles and
      tumor necrosis factor alpha (TNF-alpha) on the expressions of MMP-1, 2, 3 in
      human synovial cells, so as to explore the possible mechanism of osteolysis post
      operation of metal-on-metal total joint arthroplasty in human synovial cells
      induced by Ti particles. In vitro cell cultures, human synovial cells were
      treated by Ti particles and/or TNF-alpha. The total RNA was isolated at 2 hours
      after the treatment. The gene expression of MMP-1, 2, 3 was analyzed by Semi
      quantitative Reverse-transcriptional PCR and quantitative real-time PCR. Cell
      supernatant was collected at 12, 24, 48 hours after the treatment and Gelatin
      zymography was performed to detect the activity of MMP-2. Compared to those in
      the control group (untreated), Ti particles and TNF-alpha increased the gene
      expression of MMP-1, 2, 3 respectively (P < 0.05), and the effect of combination
      of the two was even more significant (P < 0.01). The trend of activities of MMP-2
      is similar with gene expression. Ti particles and TNF-alpha increased MMP-2
      activities by 1.3 times and 1.5 times respectively (P < 0.05), and the
      combination of the two increased by 1.7 times (P < 0.01). Ti particles and TNF
      alpha-induced the stimulation of MMP-1, 2, 3 expressions and MMP-2 activities in
      human knee joint synovial cells may be involved in aseptic loosening after metal
      on-metal arthroplasty through increasing the degradation of bone matrix and
      declining of osseous support structure mechanics.

PMID- 24459965
TI  - [Research on the coupling expansion deformation behavior of coronary stainless
      steel stent in vitro].
AB  - We analyzed coupling expansion process of three different structures of stainless
      steel (SUS-316LI) stents by using finite element method (FEM) simulation in this
      study. Firstly we made specific analysis and comparison between three stents of
      deformation and stress-strain distribution in the coupling expansion process and
      then we described the shortening rate, radial bounce rate, expand nonuniformity,
      safety factor and other biological mechanics performance of the three stents
      quantitatively. And finally we analyzed the influencing factors and the best
      structure of the three kinds of the stainless steel stent comprehensively.
      Through all the processes, we have verified the rationality of the finite element
      simulation result by using the expansion test in vitro.

PMID- 24459966
TI  - [Manual chest compression depth estimation based on integration reset mechanism].
AB  - To realize the measurement of the chest compression depth during the
      administration of manual cardiopulmonary resuscitation, two 3-axis digital
      accelerometers were applied for chest compression acceleration and environment
      acceleration acquisition, with one placed in the chest compression sensor pad,
      and the other placed in the back sensor pad. Then double integration was made for
      the acceleration-to-depth conversion with both of the accelerations after
      preprocessing. The method further included integration reset mechanism based on
      compression force, with the force point of a pre-determined threshold and the
      maximum force point as the starting point and the ending point of the
      integration, respectively. Moreover, a software compensation algorithm was
      implemented to further increase the accuracy of the depth estimation and
      reliability of the acceleration. The final performance of the compression depth
      estimation is within +/- 0.6 cm with 95% confidence of a total of 283
      compressions. Accurate and real-time estimation of chest compression depth
      greatly facilitates the control of compression depth for the lifesaver during
      manual cardiopulmonary resuscitation.

PMID- 24459967
TI  - [A comparative study on three-dimensional movement of anterior teeth between
      applying MDD appliances and applying three common fixed appliances in the initial
      alignment stage].
AB  - Typodont models of bilateral canines gingival displaced vertically for 3 mm and
      bilateral lateral incisors palatal displaced horizontally for 3 mm are made and
      every kind of the two kind models was divided into four groups: MDD, MBT, self
      ligating and Tip-Edge. Each group of the two kinds of models had 5 models, so a
      total of 40 models for the two kinds of models were set up. The experimental
      models were aligned with a 0.30 mm of nickel titanium round wire in a water-bath
      with constant temperature 45 degrees C for 30 minutes. The three-dimensional
      digital images of the experimental models before and after the water bath were
      obtained by scanning with the three dimensional optical scanner ATOS. Geomagic
      software was used to overlap the digital images taken before and after the water
      bath treatment. The vertical changes of sign points of canines, the movements of
      sign points of lateral incisors in the sagittal plane and the horizontal plane
      were quantified by using the Color map. The data was then processed by a two
      factor analysis of variance by using SAS 9.2 software package. Analysis of the
      results shows that the vertical changes of sign points of canines , the movements
      of sign points of lateral incisors in the sagittal plane and the horizontal plane
      of MDD group are all less than those in the other three groups, a statistically
      significant difference (P < 0.0001). And the size of the teeth displacement is
      directly related to the size of orthodontic force on the typodont models. Thus
      the preliminary results suggest that MDD appliance might have advantages of light
      force in the alignment stage, and that the possible relevant factors are the
      improvement of its sub-slot and the single ligation wing design.

PMID- 24459968
TI  - [Effects of extracellular matrix protein micropatterns on osteoblast cell
      adhesion and spreading].
AB  - The main purpose of the present study was to investigate the cell behaviors of
      rat primary osteoblast cells on extracellular matrix (ECM) protein micropatterns.
      For this purpose, a series of fibronectin micropatterns with different shapes and
      varying dimensions were created on polystyrene (PS) surfaces by microcontact
      printing. The results of confocal laser scanning microscopy (CLSM) images
      indicated that excellent micropatterns were successfully obtained. These protein
      patterns were stable during the cell culture. The cell experiments suggested that
      the osteoblast cells preferentially attached onto protein-functionalized areas
      and displayed different cell shape and spreading behavior on different protein
      micropatterns. The protein micropatterns can significantly influence the cell
      adhesion, spreading, alignment and orientation and so on. Therefore, this work
      can be used to modify biomaterial surfaces, especially that of bone-implant
      biomaterials, to effectively control cell behavior. It further contributes to
      clarify the interfacial biological behaviors between biomaterials and osteoblast
      and can provide the cues for development of bone implantable materials which is
      able to modulate osteoblast cell growth behavior.

PMID- 24459969
TI  - [Effects of freeze-drying process on polymerized human placenta hemoglobin].
AB  - The present study was aimed to investigate the influence of freeze-drying on the
      quality of polymerized human placenta hemoglobin (PolyPHb). The PolyPHb solution
      was freeze-drying under suitable conditions. Hemoglobin concentration,
      methemoglobin (MetHb) content, UV spectrum, Fe3 content, oxygen-carrying
      capacity, pH, the average molecular weight and its distribution, circular
      dichroism, oxygen equilibrium curve and other indicators were measured before and
      after freeze-drying. The appearance, residual water content, rehydration time of
      the lyophilized product were also evaluated. The results showed that there was no
      significant difference on all the indicators measured above, which indicated that
      freeze-drying process had no effect on the physical and chemical properties of
      PolyPHb, as well as on its biological activity. Therefore, the properties of
      PolyPHb were stable during this freeze-drying process and could be preserved
      after such freeze-drying process.

PMID- 24459970
TI  - [The preparation and bioactivity assessment of gene recombinant fibrin-binding
      brain derived neurotrophic factor].
AB  - Using the E. coli, we fabricated the gene reconstructed brain derived
      neurotrophic factor with a fibrin binding domain (FBD-BDNF). We then tested the
      neurotrophic bioactivity and fibrin-binding ability of the FBD-BDNF. The E. coli
      was used to express the recombinant protein. The inclusion body was purified with
      column chromatography and renaturated to construct the right 3D formation. In
      this study, we successfully fabricated the FBD-BDNF and tested the binding
      ability and neurotrophic activity. The results demonstrated that FBD-BDNF had
      special binding ability of fibrin and significant neurotrophic activity for DRG
      cells. FBD-BDNF could have a promising application prospect in nerve tissue
      engineering.

PMID- 24459971
TI  - [A new method of isolating and culturing rabbit osteoblasts in vitro].
AB  - To establish an experimental model of osteoblasts to easily cause calcification
      of bone matrix in vitro, we took cranium of a newborn rabbit out under an aseptic
      condition, removed the connective tissue of the bony suture, and cut the cranium
      freely into the fragments of not more than 1 mm2. The we isolated and cultured
      the osteoblasts using tissue explant method. We observed growth status of primary
      osteoblasts and subcultured osteoblasts using inverted microscope. Then we
      conducted enzyme staining and alizarin red staining for the third generation of
      osteoblasts to detect the alkaline phosphatase (ALP) expression and calcified
      nodules. The result showed that there were calcified nodules or calcification
      formed after the primary osteoblasts climbing out from the bone for 1 week, and
      each generation of osteoblasts had the similar calcification with the primary
      osteoblasts, and there was an increase in calcified nodules after the continuous
      culture. There was a strong expression of ALP in the plasma membrane of
      osteoblasts. The calcified nodules were red with alizarin red staining. It is
      well concluded that osteoblasts isolated with this method easily cause
      calcification, and can be used as a new experimental model.

PMID- 24459972
TI  - [Separation algorithm of overlapped protein spots based on shape
      characteristics].
AB  - In order to detect the overlapped and clustered protein spots in protein gel
      images, we suggest an auto-separating algorithm based on the shape
      characteristics in this paper. Firstly, we used a marker-controlled watershed
      algorithm to detect the initial outline of the protein spots in application of
      the method. Secondly, we extracted shape markers adaptively by combining local
      minima depth and shape characteristics information, and calculated the shape
      distance image according to these shape markers. Then, we imposed these shape
      markers on the shape distance image as its local minima. Finally, we applied the
      watershed algorithm again on the modified shape distance image to separate the
      overlapped spots accurately. The experiments on the synthetic gel image and the
      different types of real gel images showed that compared with other improved
      watershed algorithm, the proposed one had a higher correct separation rate with
      an error less than 6%, and better separation results of overlapped spots.

PMID- 24459973
TI  - [Epileptic EEG signal classification based on wavelet packet transform and
      multivariate multiscale entropy].
AB  - In this paper, a new method combining wavelet packet transform and multivariate
      multiscale entropy for the classification of epilepsy EEG signals is introduced.
      Firstly, the original EEG signals are decomposed at multi-scales with the wavelet
      packet transform, and the wavelet packet coefficients of the required frequency
      bands are extracted. Secondly, the wavelet packet coefficients are processed with
      multivariate multiscale entropy algorithm. Finally, the EEG data are classified
      by support vector machines (SVM). The experimental results on the international
      public Bonn epilepsy EEG dataset show that the proposed method can efficiently
      extract epileptic features and the accuracy of classification result is
      satisfactory.

PMID- 24459974
TI  - [Research on optimization of imaging system of the hand vein optical properties].
AB  - Due to the difficulties of the copying, vein identification has developed rapidly
      in recent years. The light source selection directly affects the image quality.
      This paper acquired by experiment the reflectivities of vein and non-vein
      irradiation with different wavelengths of near infra-red. Comparing the strength
      of reflectivities of various wave lengths, we found that there were the strongest
      contrasts between vein and non-vein in the 810 nm, and 810 nm near infra-red was
      suitable to a vein imaging light source. Finally, clear hand vein images were
      obtained with the selected light source.

PMID- 24459975
TI  - [A practical multi-modality medical image registration solution].
AB  - In medical imaging field, doctors often complete the intra-subject registration
      of multi modality images by choosing a pair of anatomic landmarks. It is hard to
      choose the same landmark accurately in different imaging modality. For multi
      modality image registration, mutual information measure is widely used because it
      suffers little from the difference among different modalities, but it has
      disadvantages of large amount of calculation and slow converges. In this paper,
      considering the convenience in practice, we firstly register different modality
      images by choosing a pair of corresponding landmarks. In order to decrease the
      error during choosing the landmarks, we further do the registration using mutual
      information method. The advantage of this solution is that the landmark based
      registration presents a good starting point for further mutual information (MI)
      registration, while the MI method decreases the difficulty of choosing landmarks.
      Experimental results showed that this registration solution was fast, accurate,
      and would have a good clinical potential application in the future.

PMID- 24459976
TI  - [A preliminary clinical study on endoscopic measurement of lesion area with the
      method of digital image processing technology].
AB  - It is of great importance to measure the lesion area in scientific research and
      clinical practice. The present study aims to solve barrel distortion and measure
      lesion area with the technology of computer visualization. With the ultimate
      purpose to obtain the precise lesion area, the study, based on the original
      endoscopy system and digital image processing technology, dealt with the
      correction of barrel distortion by lens adjustment, calculated the gastric ulcer
      area with the aid of Qt database and finally developed an image processing
      software--Endoscope Assistant (EAS). The results showed that the EAS was accurate
      in vitro. It was employed to measure the gastric ulcer area of 45 patients and
      the results were compared with the traditional formula method. It could be well
      concluded that this technology is safe, accurate and economical for measuring
      gastric ulcer area.

PMID- 24459977
TI  - [Development of standardization platform for optical density value based on an
      improved method].
AB  - Due to the high variation in test results of indirect enzyme-linked immuno
      sorbent assay (ELISA) and complicated steps involved in the process of
      standardization, a platform used for standardizing the test results from indirect
      ELISA was developed. The platform was designed based on 'Improved Standardization
      Method for Optical Density' (I-STOD). Gauss-Newton iteration was applied to
      estimate parameters in a standard formula. Programming Language VB was used for
      developing interface of platform. The results indicated that the validity of
      experiment could be verified through platform. A well determined scope of
      standardization could be generated. The sample with concentration within the
      scope was standardized and the degree of dilution was calculated for those
      outside the scope. The platform was successfully developed which normalized the
      process of standardization. The function provides the researchers with an
      effective and convenient tool for quickly achieving standardization of ELISA test
      results.

PMID- 24459978
TI  - [Construction and eukaryotic expression of PVAX1-hPV58mE6E7fcGB composite gene
      vaccine].
AB  - To construct and express a composite gene vaccine for human papillomavirus
      58(HPV58)-associated cervical cancer, we inserted HPV58mE6E7 fusion gene into pCI
      Fc-GPI eukaryotic expression vector, constructing a recombinant plasmid named pCI
      sig-HPV58mE6E7-Fc-GPI. Then we further inserted fragment of sig-HPV58mE6E7Fc-GPI
      into the novel vaccine vector PVAX1-IRES-GM/B7, constructing PVAX1-HPV58mE6E7FcGB
      composite gene vaccine. PVAX1-HPV58mE6E7FcGB vaccine was successfully constructed
      and identified by restriction endonuclease and sequencing analysis. Eukaryotic
      expression of fusion antigen sig-HPV58mE6E7-Fc-GPI and molecular ad-juvant GM-CSF
      and B7. 1 were proved to be realized at the same time by flow cytometry and
      immunofluorescence. So PVAX1-HPV58mE6E7FcGB can be taken as a candidate of
      therapeutic vaccine for HPV58-associated tumors and their precancerous
      transformations.

PMID- 24459979
TI  - [Establishment of a novel abdominal heart transplantation model of mice].
AB  - This paper is aimed to establish a novel abdominal heart transplantation model in
      mice and to generalize the experience of the successful cases. The thoracic
      inferior vena cava instead of pulmonary artery was employed to reconstruct the
      outflow tract of the graft heart (in the new method group, 82 cases). Meanwhile,
      in other 47 cases as the control group, traditional anastomosis was used between
      pulmonary artery of the graft and vena cava of the recipient. The recipient
      surgery time, vena cava-vena cava anastomosis time, graft cold ischemia time and
      graft re-beating time were (41.5 +/- 1. 5) min, (8.4 +/- 0.6) min, (32.3 +/- 0.4)
      min and (1.5 +/- 0.2) min respectively. All the above data were statistically
      superior to those in the traditional method group (P < 0.001 or P < 0.05). The
      survival rate of 100 d post surgery in the new method group was 93. 9%.
      Meanwhile, the cardiac tissue remained almost normal examined by HE and Picro
      sirus red staining. Therefore, the novel model can facilitate the anastomosis of
      the outflow tract in recipient operation in mouse heart transplantation model.

PMID- 24459980
TI  - [Progress in the application of conducting polymer in glucose biosensor].
AB  - Conducting polymers have stable long-chain structure and good electrical
      conductivity. They have been used in various types of biosensors because of their
      excellent characteristics of the immobilization and electrical signal
      transmission. In recent years, researchers mainly study on improving its micro
      nano structures and its signal conductivity to enhance its effect on the enzyme
      immobilization and signal conductive properties. This paper reviews firstly the
      application of conducting polymer on enzyme-immobilized glucose biosensor and the
      new technologies and methods in this field. This paper also points out the future
      application of conducting polymers in enzyme immobilization and biosensor
      preparation areas.

PMID- 24459981
TI  - [Research progress of multi-model medical image fusion and recognition].
AB  - Medical image fusion and recognition has a wide range of applications, such as
      focal location, cancer staging and treatment effect assessment. Multi-model
      medical image fusion and recognition are analyzed and summarized in this paper.
      Firstly, the question of multi-model medical image fusion and recognition is
      discussed, and its advantage and key steps are discussed. Secondly, three fusion
      strategies are reviewed from the point of algorithm, and four fusion recognition
      structures are discussed. Thirdly, difficulties, challenges and possible future
      research direction are discussed.

PMID- 24459982
TI  - [Application of finite element analysis in Chinese cervical manipulation
      biomechanics].
AB  - Clinical advantages of Chinese spinal manipulation therapy (CSMT) were recognized
      for spinal chronic lesions of soft tissues and bones, such as cervical
      spondylosis, etc. However, the security of CSMT and the hypotheses of practice
      mechanisms were questioned for lacking of the relevant basic researches.
      Researches have proved that these methods could be used to observe the dynamic
      effects of spine with application of finite element analysis (FEA) computer
      technology. Combining with other biomechanical experimental methods and applying
      advanced FEA technology for mechanical problems of CSMT, we may not only find the
      mechanisms of action and provide theoretical supports for the traditional Chinese
      therapy, but also standardize the key techniques and optimize the treatment
      options improving clinical outcomes, and even promote spreading of CSMT. Computer
      models are ideally suited for studying phenomena that cannot be satisfactorily
      investigated with other models. However, computer models of CSMT practice remain
      to be further refined. The results which had been acquired so far not only
      verified some of the traditional points of view, but also revised and specified
      some perspectives of the past. This paper intends to review FEA studies with
      Chinese cervical manipulation therapy (CCMT) for cervical spinal chronic lesions
      of soft tissues and bones, involving different effects for cervical spine joints
      (pulling/traction and thrusting) with practice techniques and cervical spine soft
      tissues (including vessels and its hemodynamics, muscles and fasciae, etc).

PMID- 24459983
TI  - [Research progress of techniques of 7 T MRI system in brain imaging].
AB  - 7 T high field magnetic resonance imaging (MRI) provides a useful tool for
      microscopic spatial resolution visualizing anatomy. In addition, it enables the
      observation and analysis of tissue metabolism and function. 7 T MRI is now
      developing fast both in its technology and in its potential prospective medical
      applications. This review introduces current applications and possible future
      developments of the 7 T MRI in the field of human brain imaging for clinical
      studies and practices.

PMID- 24459984
TI  - [Research progress of adventitious respiratory sound signal processing].
AB  - Adventitious respiratory sound signal processing has been an important
      researching topic in the field of computerized respiratory sound analysis system.
      In recent years, new progress has been achieved in adventitious respiratory sound
      signal analysis due to the applications of techniques of non-stationary random
      signal processing. Algorithm progress of adventitious respiratory sound
      detections is discussed in detail in this paper. Then the state of art of
      adventitious respiratory sound analysis is reviewed, and development directions
      of next phase are pointed out.

PMID- 24459985
TI  - [The application of recombinant Bacillus Calmette-Guerin vaccine and its vector
      in infectious disease].
AB  - Recent studies show that the vector of recombinant Bacillus Calmette-Guerin
      (rBCG) has a series of advantages. With exogenous gene and vaccine in one
      inoculation, it can obtain strong and persistent immune response at one time so
      that BCG is considered as a kind of ideal vector for live recombinant vaccine.
      This review outlines the application of rBCG vaccine and its vector in infectious
      diseases caused by bacteria, viruses, other microorganisms and parasites.

PMID- 24459986
TI  - An isothermal titration and differential scanning calorimetry study of the G
      quadruplex DNA-insulin interaction.
AB  - The binding of insulin to the G-quadruplexes formed by the consensus sequence of
      the insulin-linked polymorphic region (ILPR) was investigated with differential
      scanning calorimetry (DSC) and isothermal titration calorimetry (ITC). The
      thermal denaturation temperature of insulin was increased by almost 4  degrees C
      upon binding to ILPR G-quadruplex DNA as determined by DSC. The thermodynamic
      parameters (K(D), DeltaH, DeltaG, and DeltaS) of the insulin-G-quadruplex complex
      were further investigated by temperature-dependent ITC measurement over the range
      of 10-37  degrees C. The binding of insulin to the ILPR consensus sequence
      displays micromolar affinity in phosphate buffer at pH 7.4, which is mainly
      driven by entropic factors below 25  degrees C but by enthalpic terms above 30 
      degrees C. The interaction was also examined in several different buffers, and
      results showed that the observed DeltaH is dependent on the ionization enthalpy
      of the buffer used. This indicates proton release upon the binding of G
      quadruplex DNA to insulin. Additionally, the large negative change in heat
      capacity for this interaction may be associated with the dominant hydrophobicity
      of the amino acid sequence of insulin's beta subunit, which is known to bind to
      the ILPR G-quadruplex DNA.

PMID- 24459987
TI  - Aggrecan-mimetic, glycosaminoglycan-containing nanoparticles for growth factor
      stabilization and delivery.
AB  - The direct delivery of growth factors to sites of tissue healing is complicated
      by their relative instability. In many tissues, the glycosaminoglycan (GAG) side
      chains of proteoglycans like aggrecan stabilize growth factors in the
      pericellular and extracellular space, creating a local reservoir that can be
      accessed during a wound healing response. GAGs also regulate growth factor
      receptor interactions at the cell surface. Here we report the development of
      nanoparticles for growth factor delivery that mimic the size, GAG composition,
      and growth factor binding and stabilization of aggrecan. The aggrecan-mimetic
      nanoparticles are easy to assemble, and their structure and composition can be
      readily tuned to alter their physical and biological properties. We use basic
      fibroblast growth factor (FGF-2) as a model heparin-binding growth factor,
      demonstrating that aggrecan-mimetic nanoparticles can preserve its activity for
      more than three weeks. We evaluate FGF-2 activity by measuring both the
      proliferation and metabolic activity of bone marrow stromal cells to demonstrate
      that chondroitin sulfate-based aggrecan mimics are as effective as aggrecan, and
      heparin-based aggrecan mimics are superior to aggrecan as delivery vehicles for
      FGF-2. 

PMID- 24459990
TI  - Mechanisms affecting water quality in an intermittent piped water supply.
AB  - Drinking water distribution systems throughout the world supply water
      intermittently, leaving pipes without pressure between supply cycles.
      Understanding the multiple mechanisms that affect contamination in these
      intermittent water supplies (IWS) can be used to develop strategies to improve
      water quality. To study these effects, we tested water quality in an IWS system
      with infrequent and short water delivery periods in Hubli-Dharwad, India. We
      continuously measured pressure and physicochemical parameters and periodically
      collected grab samples to test for total coliform and E. coli throughout supply
      cycles at 11 sites. When the supply was first turned on, water with elevated
      turbidity and high concentrations of indicator bacteria was flushed out of pipes.
      At low pressures (<10 psi), elevated indicator bacteria were frequently detected
      even when there was a chlorine residual, suggesting persistent contamination had
      occurred through intrusion or backflow. At pressures between 10 and 17 psi,
      evidence of periodic contamination suggested that transient intrusion, backflow,
      release of particulates, or sloughing of biofilms from pipe walls had occurred.
      Few total coliform and no E. coli were detected when water was delivered with a
      chlorine residual and at pressures >17 psi. 

PMID- 24459992
TI  - Spatiotemporal expression of DNA demethylation enzymes and histone demethylases
      in bovine embryos.
AB  - Fertilization in bovines causes profound changes in the epigenetic profile that
      affect both DNA methylation patterns and posttranslational histone modifications.
      These dynamic changes have a great potential for activating pluripotency genes
      and unfolding certain chromatin regions to recruit different transcription
      factors. Surprisingly, while the fundamental function of epigenetic remodeling is
      well understood, the bases of the process are still unknown. Recent developments
      in epigenetics suggest a multistep demethylation process that would imply the
      prior modification of the methylated cytosine or methyl group, followed by a DNA
      repair mechanism implicating enzymes such as activation-induced cytidine
      deaminase (AICDA) and ten-eleven translocation (TET) dioxygenase. Their functions
      seem to differ from one species to the other, and they are not yet well
      characterized in large mammals. Histones have, for their part, many associated
      and specific lysine demethylases (KDM). Their expression profile in large mammals
      is not well characterized. We have been interested in characterizing the
      spatiotemporal expression profile for each of the genes studied to increase our
      understanding of the molecular interactions following fertilization in early
      bovine embryo stages. Bovine oocytes and embryos at various preimplantation
      stages were collected following in vitro fertilization protocol. Total RNA for
      AICDA, TET1, TET2, TET3, KDM3A, KDM4A, KDM4C, and KDM5B was extracted, reverse
      transcribed into cDNA, and amplified by real-time PCR. Other embryo pools were
      collected, and protein localization of the genes studied was characterized. TET3
      dioxygenase was present in the very first embryo stages, in contrast to TET1 and
      AICDA. Histone demethylases KDM3A, KDM4A, and KDM4C were expressed before and
      after embryonic genome activation, whereas KDM5B was mainly expressed during the
      blastocyst period. DNA demethylation following fertilization in bovines is not
      accomplished by AICDA but most probably by TET3. Histone demethylation is carried
      out by, among others, KDM3A, KDM4A, and KDM4C, which could act in sequence to
      demethylate histones prior to DNA demethylation of the female chromosomes.

PMID- 24459991
TI  - Sox9 reprogrammed dermal fibroblasts undergo hypertrophic differentiation in
      vitro and trigger endochondral ossification in vivo.
AB  - Strategies for bone regeneration are undergoing a paradigm shift, moving away
      from the replication of end-stage bone tissue and instead aiming to recapture the
      initial events of fracture repair. Although this is known to resemble
      endochondral bone formation, chondrogenic cell types with favorable proliferative
      and hypertrophic differentiation properties are lacking. Recent advances in
      cellular reprogramming have allowed the creation of alternative cell populations
      with specific properties through the forced expression of transcription factors.
      Herein, we investigated the in vitro hypertrophic differentiation and in vivo
      tissue formation capacity of induced chondrogenic cells (iChon cells) obtained
      through direct reprogramming. In vitro hypertrophic differentiation was detected
      in iChon cells that contained a doxycycline-inducible expression system for Klf4,
      cMyc, and Sox9. Furthermore, endochondral bone formation was detected after
      implantation in nude mice. The bone tissue was derived entirely from host origin,
      whereas cartilage tissue contained cells from both host and donor. The results
      obtained highlight the promise of cellular reprogramming for the creation of
      functional skeletal cells that can be used for novel bone healing strategies.

PMID- 24459993
TI  - When should you test for and treat hypoglycemia in prehospital seizure patients?
AB  - OBJECTIVES: Seizure is a frequent reason for activating the Emergency Medical
      System (EMS). Little is known about the frequency of seizure caused by
      hypoglycemia, yet many EMS protocols require glucose testing prior to treatment.
      We hypothesized that hypoglycemia is rare among EMS seizure patients and glucose
      testing results in delayed administration of benzodiazepines. METHODS: This was a
      retrospective study of a national ambulance service database encompassing 140 ALS
      capable EMS systems spanning 40 states and Washington DC. All prehospital calls
      from August 1, 2010 through December 31, 2012 with a primary or secondary
      impression of seizure that resulted in patient treatment or transport were
      included. Median regression with robust and cluster (EMS agency) adjusted
      standard errors was used to determine if time to benzodiazepine administration
      was significantly related to blood glucose testing. RESULTS: Of 2,052,534 total
      calls, 76,584 (3.7%) were for seizure with 53,505 (69.9%) of these having a
      glucose measurement recorded. Hypoglycemia (blood glucose <60 mg/dL) was present
      in 638 (1.2%; CI: 1.1, 1.3) patients and 478 (0.9%; CI: 0.8, 1.0) were treated
      with a glucose product. A benzodiazepine was administered to 73 (11.4%; CI: 9.0,
      13.9) of the 638 hypoglycemic patients. Treatment of seizure patients with a
      benzodiazepine occurred in 6,389 (8.3%; CI: 8.1, 8.5) cases and treatment with a
      glucose product occurred in 975 (1.3%; CI: 1.2, 1.4) cases. Multivariable median
      regression showed that obtaining a blood glucose measurement prior to
      benzodiazepine administration compared to no glucose measurement or glucose
      measurement after benzodiazepine administration was independently associated with
      a 2.1 minute (CI: 1.5, 2.8) and 5.9 minute (CI: 5.3, 6.6) delay to benzodiazepine
      administration by EMS, respectively. CONCLUSIONS: Rates of hypoglycemia were very
      low in patients treated by EMS for seizure. Glucose testing prior to
      benzodiazepine administration significantly increased the median time to
      benzodiazepine administration. Given the importance of rapid treatment of seizure
      in actively seizing patients, measurement of blood glucose prior to treating a
      seizure with a benzodiazepine is not supported by our study. EMS seizure
      protocols should be revisited.

PMID- 24459996
TI  - Preparation for practice: self study modules in medical surgical nursing.

PMID- 24459994
TI  - A universal law for cell uptake of one-dimensional nanomaterials.
AB  - Understanding cell interaction with one-dimensional nanomaterials, including
      nanotubes, nanowires, nanofibers, filamentous bacteria, and certain nanoparticle
      chains, has fundamental importance to many applications such as biomedical
      diagnostics, therapeutics, and nanotoxicity. Here we show that cell uptake of one
      dimensional nanomaterials via receptor-mediated endocytosis is dominated by a
      single dimensionless parameter that scales with the membrane tension and radius
      of the nanomaterial and inversely with the membrane bending stiffness. It is
      shown that as cell membrane internalizes one-dimensional nanomaterials the uptake
      follows a near-perpendicular entry mode at small membrane tension but it switches
      to a near-parallel interaction mode at large membrane tension. 

PMID- 24459999
TI  - Intuitive eating: associations with physical activity motivation and BMI.
AB  - PURPOSE: To determine whether university women who demonstrated internal
      motivation related to eating behavior may also be internally motivated to
      participate in regular physical activity (PA) and have a lower body mass index
      (BMI) when controlling for age. Traditional approaches for health promotion
      related to healthy weight include restrictive eating and exercise prescription.
      Examining motivation for eating and PA may prove an effective alternative for
      achieving or maintaining healthy weight for university women. DESIGN: Design was
      a cross-sectional study. SETTING: Study setting was a large, public university in
      the western United States. Subjects . Study subjects were 200 undergraduate women
      with a mean age of 19 years, mostly white (90%) and of healthy weight (69%, with
      a BMI range of 18.5-24.9). MEASURES: Study measures were the Intuitive Eating
      Scale and the Behavioral Regulation in Exercise Questionnaire. ANALYSIS:
      Correlations and regression models were used. Intuitive eating was examined in
      the sample as a whole and among subgroups of respondents grouped based on tertile
      rankings of intuitive eating scores. RESULTS: There was evidence that women who
      demonstrated internal motivation related to eating were also internally motivated
      to participate in regular PA. Women who reported being internally motivated to
      eat were significantly more likely to engage in PA for pleasure and to view PA as
      part of their self-concept. Women who reported high levels of intuitive eating
      had significantly lower BMI scores than those reporting medium or low levels when
      controlling for age. CONCLUSION: For women to achieve or maintain a healthy
      weight, it may be best for health professionals to examine motivation for eating
      and PA rather than the encouragement of restrictive eating and exercise
      prescriptions.

PMID- 24459998
TI  - Children's, their guardians', and health care professionals' perceptions of child
      overweight in relation to children's weight loss attempts.
AB  - PURPOSE: To examine accuracy of children's, their guardians', and health care
      professionals' (HCPs') perceptions of child overweight and obesity, the degree of
      agreement between their perceptions, and relationships with weight loss attempts
      among overweight or obese children. DESIGN: Cross-sectional study using 2005-2010
      National Health and Nutrition Examination Survey. SETTING: United States.
      SUBJECTS: Out of 4691 children and adolescents, ages 8 to 15 years, 16.4% were
      overweight (body mass index [BMI] percentiles 85-94.99) and 19.3% were obese (BMI
      percentiles >=95). MEASURES: Age and sex-specific BMI percentiles; responses of
      adult proxies (guardians) on whether they considered their child overweight and
      whether an HCP had ever told them that their child was overweight; responses of
      children and adolescents on their self-perceived weight status and whether they
      were trying to lose weight; children's and guardians' socio-demographic
      characteristics. ANALYSIS: Weighted percentages; sensitivities and Cohen's
      kappas; adjusted prevalence ratios. RESULTS: Children, their guardians, and HCPs
      underestimated child's actual overweight or obesity status. Little agreement
      existed between overweight or obese children, their parents, and HCPs on whether
      these children were overweight or obese. Overweight and obese children perceived
      as such by themselves, their guardians, and HCPs were 88% and 32%, respectively,
      more likely to attempt weight loss based on multivariable analyses. CONCLUSION:
      Accurate and shared perceptions of adiposity in children and adolescents between
      children themselves, their guardians, and HCPs are positively associated with
      weight loss attempts among overweight or obese children in the United States.

PMID- 24460000
TI  - A cluster randomized trial of alcohol prevention in small businesses: a cascade
      model of help seeking and risk reduction.
AB  - PURPOSE: The current study adapted two workplace substance abuse prevention
      programs and tested a conceptual model of workplace training effects on help
      seeking and alcohol consumption. DESIGN: Questionnaires were collected 1 month
      before, 1 month after, and 6 months within a cluster randomized field experiment.
      SETTING: Texas small businesses in construction, transportation, and service
      industries. SUBJECTS: A total of 1510 employees from 45 businesses were randomly
      assigned to receive no training or one of the interventions. INTERVENTION: The
      interventions were 4-hour on-the-job classroom trainings that encouraged healthy
      lifestyles and seeking professional help (e.g., from the Employee Assistance
      Program [EAP]). The Team Awareness Program focused on peer referral and team
      building. The Choices in Health Promotion Program delivered various health topics
      based on a needs assessment. MEASURES: Questionnaires measured help-seeking
      attitudes and behavior, frequency of drinking alcohol, and job-related incidents.
      ANALYSIS: Mixed-model repeated-measures analyses of covariance were computed.
      RESULTS: Relative to the control group, training was associated with
      significantly greater reductions in drinking frequency, willingness to seek help,
      and seeking help from the EAP. After including help-seeking attitudes as a
      covariate, the correlation between training and help seeking becomes
      nonsignificant. Help-seeking behavior was not correlated with drinking frequency.
      CONCLUSION: Training improved help-seeking attitudes and behaviors and decreased
      alcohol risks. The reductions in drinking alcohol were directly correlated with
      training and independent from help seeking.

PMID- 24460001
TI  - Effect of a park-based after-school program on participant obesity-related health
      outcomes.
AB  - PURPOSE: The objective of this study was to examine the effect of a structured
      after-school program housed in a large county parks system on participant health
      and wellness outcomes. DESIGN: Longitudinal cohort study over one school year
      (fall 2011-spring 2012). SETTING: A total of 23 county parks in Florida.
      SUBJECTS: Children ages 5 to 16 (N = 349, 55% non-Hispanic black, 40% Hispanic,
      mean age 8.9 years). INTERVENTION: An after-school program called Fit-2-Play that
      integrates daily standardized physical activity and health and wellness education
      components. MEASURES: Preintervention (August/September 2011) and
      postintervention (May/June 2012) anthropometric, systolic/diastolic blood
      pressure, fitness, and health and wellness knowledge measurements were collected.
      ANALYSIS: Comparison of pre-post outcome measure means were assessed via general
      linear mixed models for normal-weight (body mass index [BMI] <85th percentile for
      age and sex) and overweight/obese (BMI >=85th percentile for age and sex)
      participants. RESULTS: The overweight/obese group significantly decreased their
      mean (1) BMI z score (2.0 to 1.8, p < .01) and (2) subscapular skinfold
      measurements (19.4 to 17.5 mm, p < .01) and increased (1) mean laps on the
      Progressive Aerobic Cardiovascular Endurance Run test (10.8 to 12.5, p = .04) and
      (2) percentage with normal systolic blood pressure (58.1% to 71.0%, p = .03) from
      pretest to posttest. On average, participants significantly improved their health
      and wellness knowledge over the school year (p < .01). Normal-weight participants
      maintained healthy BMI ranges and significantly increased fitness levels.
      CONCLUSION: Findings suggest that the Fit-2-Play after-school programs can be a
      significant resource for combating childhood obesity and instilling positive
      physical health in children, particularly among ethnic and socioeconomically
      diverse communities.

PMID- 24460002
TI  - Perceptions about energy drinks are associated with energy drink intake among
      U.S. youth.
AB  - PURPOSE: Energy drinks are growing in popularity among youth because of their
      stimulant properties. However, they can increase blood pressure and are
      associated with serious consequences such as cardiac arrest. This study examined
      the associations between energy drink perceptions and energy drink consumption
      among youth. DESIGN: The design was a cross-sectional study using the YouthStyles
      Survey 2011. SETTING: The online survey was administered at home. SUBJECTS:
      Subjects were youths aged 12 to 17 years in the summer of 2011 (n = 779).
      MEASURES: Energy drink consumption, perceptions about energy drinks, and
      sociodemographic and behavioral variables were measured. ANALYSIS: Chi-square and
      multivariable logistic regression analyses were used. RESULTS: Overall, 9% of
      youth drank energy drinks, 19.5% agreed that energy drinks are safe drinks for
      teens, and 12.5% agreed that energy drinks are a type of sports drink. The
      proportion of youth consuming energy drinks once per week or more was highest
      among youth aged 16 to 17 years and among those who are physically active three
      to six times a week. The odds for drinking energy drinks once per week or more
      was higher among youth who agreed that energy drinks are safe drinks for teens
      (odds ratios [OR] = 7.7, 95% confidence intervals [CI] =3.6, 16.4) and among
      those who agreed that energy drinks are a type of sports drink (OR = 5.0, 95% CI
      = 2.4, 10.7). CONCLUSIONS: These findings suggest that many youth may be unaware
      or misinformed about the potential health effects and nutritional content of
      energy drinks. Efforts to improve education among youth about the potential
      adverse effects of consuming energy drinks are needed.

PMID- 24460003
TI  - A breast health educational program for Chinese-American women: 3- to 12-month
      postintervention effect.
AB  - PURPOSE: To test the efficacy of a culturally targeted breast cancer screening
      educational program in increasing mammogram completion in Chinese-American
      immigrant women. DESIGN: Randomized controlled study. SETTING: Chinese
      communities, Portland, Oregon. SUBJECTS: From April 2010 to September 2011, 300
      women were randomized to receive a theory-based, culturally targeted breast
      cancer screening educational intervention (n = 147) or a mammography screening
      brochure published by the National Cancer Institute (n = 153). INTERVENTION: The
      two-part intervention consisted of group teaching with targeted, theory-based
      messages followed by individual counseling sessions. MEASURES: Mammography
      completion, perceived susceptibility, perceived benefits, perceived barriers,
      perceived cultural barriers, and demographic variables. ANALYSIS: A 2 * 3 mixed
      logistic model was applied to determine odds ratio of mammogram completion.
      RESULTS: Behavior changed in both groups, with a total of 170 participants
      (56.7%) reporting a mammogram at 12 months. The logistic model indicated
      increased odds of mammogram completion in the intervention compared to the
      control group at 3, 6, and 12 months. When controlling for marital status, age,
      and age moved to the United States, the intervention group was nine times more
      likely to complete mammograms than the control group. CONCLUSION: The culturally
      targeted educational program significantly increased mammogram use among Chinese
      immigrant women. Further testing of effectiveness in larger community settings is
      needed. The intervention may also serve as a foundation from which to develop
      education to increase cancer screening among other minority subgroups.

PMID- 24460004
TI  - The association between sport participation and dietary behaviors among fourth
      graders in the school physical activity and nutrition survey, 2009-2010.
AB  - PURPOSE: To determine the association between youth sport team participation and
      dietary behaviors among elementary school-aged children. DESIGN: Cross-sectional
      survey. SETTING: Public schools in Texas during 2009-2010. SUBJECTS: A total of
      5035 ethnically diverse fourth graders. MEASURES: Participation in organized
      sports teams, consumption of select food items (fruits, vegetables, beverages,
      sweets/snacks). ANALYSIS: Multiple logistic regression was used to assess the
      association between each food item (eaten at least once on the previous day) and
      number of sports teams as the independent class variable (0, 1 ,2, >=3),
      adjusting for body mass index physical activity, socioeconomic status, and
      ethnicity. RESULTS: Significant dose-response associations were observed between
      number of sports teams and consumption of fruits and vegetables. For boys, the
      likelihood of eating fruit and fruit-flavored drinks was significantly higher and
      the odds of drinking soda were lower with the number of teams. For girls, the
      likelihood of consuming green vegetables increased as sports teams participation
      increased, and participation was positively associated with diet soda
      consumption. A positive association was observed between the number of sports
      teams and scores on the Healthy Food Index for boys and girls. CONCLUSION: The
      findings that sports participation is associated with consumption of fruits and
      vegetables and lower consumption of soda suggest that efforts should be focused
      on supporting youth team sports to promote healthier food choices. Since sports
      are available to all ages, sports may be an important venue for promoting
      healthier dietary behaviors.

PMID- 24460005
TI  - Effect of two jumping programs on hip bone mineral density in premenopausal
      women: a randomized controlled trial.
AB  - PURPOSE: To determine the effect of two jumping programs on hip bone mineral
      density (BMD) in women. DESIGN: Randomized controlled trial. SETTING:
      Approximately 20 cities in the Mountain West. SUBJECTS: Sixty premenopausal
      women, aged 25 to 50 years, completed the intervention. INTERVENTION: Subjects
      were randomly assigned to a control group or one of two jumping groups. The Jump
      10 group performed 10 jumps with 30 seconds rest between jumps, twice daily for
      16 weeks, while the Jump 20 group performed the same protocol but with 20 jumps.
      MEASURES: Hip BMD was measured by using dual-energy x-ray absorptiometry.
      ANALYSIS: Analysis of variance and covariance. RESULTS: At 8 weeks, unadjusted
      percentage change in hip BMD was significantly different among groups (F = 5.4, p
      = .0236). Specifically, compared with controls, the Jump 20 women had
      significantly greater gains in hip BMD and the Jump 10 women had marginally
      greater improvements. Following 16 weeks of jumping, differences between the Jump
      10 and the Jump 20 groups compared with controls were significant (F = 4.2, p =
      .0444), especially after adjusting for the covariates (F = 7.3, p = .0092).
      CONCLUSION: After 16 weeks of high-impact jump training, hip BMD can be improved
      in premenopausal women by jumping 10 or 20 times, twice daily, with 30 seconds of
      rest between each jump, compared with controls.

PMID- 24460006
TI  - Does individualized health information regarding alcohol consumption affect
      consumption among risky drinkers?
AB  - PURPOSE: Studies testing the effect of physician advice on alcohol consumption in
      a noncontrolled environment have not specifically focused on risky drinkers.
      Therefore, it is possible that the estimated effect of professional health advice
      primarily reflected moderate drinkers' responses. We assessed whether
      professional health advice reduced alcohol consumption among risky and binge
      drinkers in a real-world setting. DESIGN: Retrospective cohort analysis. SETTING:
      We used 2009 Behavioral Risk Factor Surveillance System Annual Survey Data.
      SUBJECTS: Five thousand seven hundred thirty-five adult male and nonpregnant
      female risky drinkers, with hypertension or borderline hypertension, who reported
      on whether they were advised to reduce alcohol consumption. MEASURES: Dependent
      variable: respondent was currently reducing alcohol use to control hypertension
      (1 = yes; 0 = no). Primary regressor: respondent claimed to have received advice
      from a health professional on reducing alcohol consumption to control
      hypertension (1 = yes; 0 = no). ANALYSIS: The model was estimated using
      generalized maximum entropy. RESULTS: Professional health advice increased the
      probability that both risky (marginal effect [ME] = .09), and binge drinkers (ME
      = .07) reduced their alcohol consumption. CONCLUSION: Our findings indicate that
      risky drinkers can effectively be targeted with consumption advice. This has
      important policy implications given that society bears the largest cost for this
      group, whereas moderate drinkers have been found to be relatively productive and
      healthy.

PMID- 24460007
TI  - Stabilization of vitamin E-enriched nanoemulsions: influence of post
      homogenization cosurfactant addition.
AB  - Oil-in-water nanoemulsions are being used in the food, beverage, and
      pharmaceutical industries to encapsulate, protect, and deliver lipophilic
      bioactive components, such as drugs, vitamins, and nutraceuticals. However,
      nanoemulsions are thermodynamically unstable systems that breakdown over time. We
      investigated the influence of posthomogenization cosurfactant addition on the
      thermal and storage stability of vitamin E acetate nanoemulsions (VE
      nanoemulsions) formed from 10% oil phase (VE), 10% surfactant (Tween 80), 20%
      cosolvent (ethanol), and 60% buffer solution (pH 3). Addition of a nonionic
      cosurfactant (0.5% Tween 20) caused little change in droplet charge, whereas
      addition of anionic (0.5% SDS) or cationic (0.5% lauric arginate) cosurfactants
      caused droplets to be more negative or positive, respectively. Tween 20 addition
      had little impact on the cloud point of VE-nanoemulsions, but slightly decreased
      their isothermal storage stability at elevated temperatures (37  degrees C).
      Lauric arginate or SDS addition appreciably increased the cloud point, but did
      not improve storage stability. Indeed, SDS actually decreased the storage
      stability of the VE-nanoemulsions at elevated temperatures. We discuss these
      effects in terms of the influence of surfactants on droplet growth through
      Ostwald ripening and/or coalescence mechanisms. This study provides important
      information about the effect of cosurfactants on the stability of VE
      nanoemulsions suitable for use in pharmaceutical and food products. 

PMID- 24460010
TI  - Thermoreversible as well as thermoirreversible organogel formation by L-cysteine
      based amphiphiles with poly(ethylene glycol) tail.
AB  - We report here the gelation behavior of two novel L-cysteine-based amphiphiles
      bearing a poly(ethylene glycol) tail. The amphiphiles were found to form
      transparent organogels in both apolar and aprotic polar solvents at reasonably
      low concentrations. In chloroform, dichloromethane, and benzene solvents, the
      organogels are formed at room temperature without the requirement of heating
      cooling cycle due to strong hydrogen-bonding interaction between gelator
      molecules. The swelling kinetics, however, becomes faster on heating. Unlike most
      organogels of low-molecular-mass gelators, these organogels do not exhibit a gel
      to-sol transition on heating but instead become rigid when heated. Surprisingly,
      in polar solvents, the gelation required a heating-cooling cycle, and the sol-to
      gel transition was found to be reversible. The gelation abilities of the
      amphiphiles were correlated with the hydrogen-bonding parameters of the solvents.
      Intermolecular H-bonding interaction was found to be the major driving force for
      the organogelation. The morphology of the organogels was investigated by the use
      of optical as well as electron microscopy and was found to be dependent on the
      nature of solvent. The mechanical strengths of the organogels were studied by
      rheological measurements.

PMID- 24460009
TI  - Human papillomavirus infections in nonsexually active perinatally HIV infected
      children.
AB  - Although human papillomavirus (HPV) infections are common in HIV-infected adults,
      little is known about children. Our objective was to examine the prevalence of
      and risks for HPV of the oral mucosal and external genital areas in nonsexually
      active (NSA) perinatally (P) HIV+ children and compare with HIV-exposed but
      uninfected (HEU) children. A convenience sample attending a pediatric clinic were
      enrolled. Samples for HPV were obtained from the oral and anogenital areas and
      tested for one of 37 HPV types. The mean age of the 48 PHIV+ children was 14.3+/
      3.9 years vs. 6.2+/-4.8 for the 52 HEU (p<0.001). Of the 23 PHIV+ girls, 30.4%
      had anogenital and 17% had oral HPV, and of the 27 HEU girls, 2 (7.4%) anogenital
      and 0 had oral HPV. Of the boys, 4/23 (17.4%) and 1/25 (4%) PHIV+ had anogenital
      and oral HPV, respectively, and 3/24 (12.5%) and 1/25 (4%) HEU had anogenital and
      oral HPV, respectively. Rates of HPV did not differ by age among the PHIV+,
      whereas older HEU were more likely to have HPV than younger HEU (p=0.07). This
      large age gap precluded statistical comparison by HIV status. The presence of HPV
      in NSA PHIV+ children may have implications regarding HPV vaccination efficacy.

PMID- 24460011
TI  - Myeloperoxidase and its products in synovial fluid of patients with treated or
      untreated rheumatoid arthritis.
AB  - OBJECTIVE: Plasma and synovial myeloperoxidase (MPO) and its products were
      strongly associated with osteoarthritis (OA) and rheumatoid arthritis (RA). In
      addition, it is well known that there is a link between oxidative stress and
      cytokines. The present study aims at investigating the link between synovial MPO
      (and its products), interleukin (IL)-18, which is involved in the degradation of
      articular cartilage in RA, and IL-8, which is involved in recruitment and
      activation of neutrophils during inflammation. Effects of the treatment of RA on
      the biological parameters were also investigated. METHODS: Patients (n = 105)
      were studied including 39 patients with OA, 33 with RA and 33 with RA receiving a
      specific treatment. Disease activity score (DAS-28) was calculated whereas MPO
      antigen/activity, neutrophils, chloro-tyrosine (Cl-Tyr), homocitrulline (Hcit),
      IL-8, and IL-18 were measured in synovial fluid (SF) and CRP was measured in
      serum. RESULTS: DAS-28 and CRP levels were not significantly different between
      groups. MPO activity, and MPO, Cl-Tyr, and Hcit levels were significantly higher
      in SF of RA patients than OA patients. MPO specific activity (MPO
      activity/antigen ratio) was significantly lower in treated than in untreated RA
      patients as was IL-8. MPO activity and concentration were correlated with IL-8
      and IL-18 in untreated but not in treated RA patients. CONCLUSIONS: MPO level is
      related to IL-8 and IL-18 levels in untreated RA patients. A link has been shown
      between treatment and decrease of IL-8, MPO specific activity and Hcit in SF. The
      causal role of MPO in SF inflammation and how treatment can affect MPO specific
      activity need further investigations.

PMID- 24460022
TI  - Porous fluorinated SnO(2) hollow nanospheres: transformative self-assembly and
      photocatalytic inactivation of bacteria.
AB  - Highly porous surface fluorinated SnO2 hollow nanospheres (SnO2(F) HNS) were
      produced in high yield by a hydrothermal treatment of stannous fluoride in the
      presence of hydrogen peroxide. Two important processes in terms of oriented self
      assembly and in situ self-transformation were highlighted for the formation of as
      prepared SnO2(F) HNS, which were largely relying on the directing effects of
      selected specific chemical species in the present synthesis system.
      Significantly, these SnO2(F) HNS showed considerable activity in photocatalytic
      inactivation of a surface negatively charged bacterium, Escherichia coli K-12, in
      aqueous saline solution. The dominant reactive species involved in the
      inactivation process were also identified. 

PMID- 24460021
TI  - Morphological and hydrodynamic correlations with increasing outflow facility by
      rho-kinase inhibitor Y-27632.
AB  - Abstract Rho-kinase inhibitors affect actomyosin cytoskeletal networks and have
      been shown to significantly increase outflow facility and lower intraocular
      pressure in various animal models and human eyes. This article summarizes common
      morphological changes in the trabecular meshwork induced by Rho-kinase inhibitors
      and specifically compares the morphological and hydrodynamic correlations with
      increased outflow facility by Rho-kinase inhibitor, Y-27632, in bovine, monkey,
      and human eyes under similar experimental conditions. Interspecies comparison has
      shown that morphological changes in the juxtacanalicular connective tissue (JCT)
      of these 3 species were different. However, these different morphological changes
      in the JCT, no matter if it's separation between the JCT and inner wall in bovine
      eyes, or separation between the JCT cells or between the JCT cells and their
      matrix in monkey eyes, or even no separation between the inner wall and the JCT
      but a more subtle expansion of the JCT in human eyes, appear to correlate with
      the increased percent change of outflow facility. More importantly, these
      different morphological changes all resulted in an increase in effective
      filtration area, which was positively correlated with increased outflow facility
      in all 3 species. These results suggest a link among changes in outflow facility,
      tissue architecture, and aqueous outflow pattern. Y-27632 increases outflow
      facility by redistributing aqueous outflow through a looser and larger area in
      the JCT. 

PMID- 24460023
TI  - The "magnetic collar": the ultimate solution for gastroesophageal reflux?

PMID- 24460024
TI  - The diagnostic accuracy of the Forns index, platelet count and AST to Platelet
      Ratio Index derived fibrosis index for the prediction of Hepatitis C virus
      related significant liver fibrosis and cirrhosis.
AB  - AIM: To provide a simple fibrosis index combining the routine laboratory markers
      for predicting significant fibrosis (SF) and cirrhosis in patients with chronic
      HCV. METHODS: Platelet count, ALT, AST, AST to ALT Ratio, AST to Platelet Ratio
      Index (APRI), Forns index, FIB-4 and Age Platelet Index of 202 liver biopsy
      performed HCV-infected patients were reviewed. METAVIR classification was used to
      determine the stage of liver fibrosis. The predictive fibrosis index was
      constructed by multiple linear regression analysis (- 2.948 + 0.562 * Forns index
      + 0.288 * APRI + 0.006 * platelet count [10(9)/L]). RESULTS: Median (25th-75th
      interquartile range) age was 52 (42-59) years, and 61% were male. 65.8% (n = 133)
      had SF (F2-F4) and 23.3% (n = 47) had cirrhosis (F4). For discrimination of SF,
      AUROCs were: Fibrosis index = 0.869, Forns index = 0.837, APRI = 0.814, platelet
      count = 0.764. For cirrhosis, AUROCs were: Fibrosis index = 0.911, Forns index =
      0.883, APRI = 0.847, platelet count = 0.827. A cut-off point of <= 1.2 for
      fibrosis index excluded SF in 89% of patients with sensitivity of 96%, while >
      2.0 predicted SF in 88% of patients with specificity of 86%. Threshold of <= 1.9
      excluded cirrhosis in 95% of patients with sensitivity of 94%, while > 2.7 showed
      cirrhosis in 88% of patients with specificity of 95%. In multivariate logistic
      regression analysis, OR (95% CI) of fibrosis index was 7.825 (3.682-16.629) for
      SF (p < 0.001) and was 8.672 (4.179-17.996) for cirrhosis (p < 0.001).
      CONCLUSION: SF and cirrhosis were predicted with accuracy of 82% and 89% and were
      excluded with accuracy of 74% and 82% using this fibrosis index which may
      potentially decrease the need for liver biopsy in 76% and 83% of patients,
      respectively.

PMID- 24460025
TI  - Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in Greek newborns: the
      Mediterranean C563T mutation screening.
AB  - Glucose-6-Phosphate Dehydrogenase (G6PD) gene is located at the X-chromosome at
      Xq28 and the disease is recessively inherited predominantly in males. More than
      400 variants have been proposed based on clinical and enzymatic studies. The aim
      of the current study was to identify C563T mutation in G6PD-deficient newborns
      and to correlate the enzyme residual activity with the presence of the mutation.
      Some 1189 full-term neonates aged 3-5 days old were tested for G6PD activity in
      dried blood spots from Guthrie cards using a commercial kit. DNA extraction from
      Guthrie cards and mutation identification among the deficient samples were
      performed with current techniques. A total of 92 (7.7%) newborns were G6PD
      deficient. In 46 (50%), the mutation C563T was identified. The residual activity
      in C563T hemizygote males (n = 28) was statistically significantly lower (1.23 +/
      0.93 U/g Hb) than that in non-C563T G6PD-deficient males (n = 25) (4.01 +/- 1.20
      U/g Hb, p < 0.0001) and in controls (13.6 +/- 2.9 U/g Hb, p < 0.0001). In C563T
      heterozygote females, the estimated enzyme activity was lower than that
      determined in non-C563T females. Male C563T hemizygotes suffer from G6PD
      deficiency and severe neonatal jaundice. G6PD activity showed statistically
      significant correlation with total bilirubin blood levels.

PMID- 24460026
TI  - Can 24-hour urine stone risk profiles predict urinary stone composition?
AB  - BACKGROUND AND PURPOSE: Distinguishing calcium oxalate from uric acid stones is
      critical to identify those patients who may benefit from dissolution therapy and
      can also help direct preventive measures for stone growth. We aim to study
      whether 24-hour urine analysis may predict the urinary stone composition.
      PATIENTS AND METHODS: We retrospectively identified patients with calcium oxalate
      and uric acid stone compositions who also had a 24-hour urine collection within 3
      months of stone analysis. Patients with calcium phosphate, cystine, and other
      stone compositions were excluded. Subjects were divided based on their stone type
      (calcium oxalate vs uric acid stones) and were compared according to demographic
      data and 24-hour urine analysis. Logistic regression analysis was performed to
      assess the association between stone composition and covariates. A nomogram was
      then constructed to predict uric acid stones over calcium oxalate stones.
      RESULTS: Of the 1163 patients identified, 1054 (90.6%) had calcium oxalate stones
      and 109 (9.4%) had uric acid stones. On logistic regression, body mass index
      (BMI) (odds ratio [OR] 1.351, 95% confidence interval [CI] 1.133-1.609; P<0.001),
      urinary sodium (OR 1.021, 95% CI 1.004-1.037; P=0.013), calcium (OR 0.987, 95% CI
      0.979-0.996; P=0.003), oxalate (OR 0.890, 95% CI 0.804-0.985; P=0.024), and uric
      acid (OR 0.989, 95% CI 0.982-0.997; P=0.005) were significant predictors for
      urinary stone composition. The nomogram with the highest concordance index (c
      index=0.855) was obtained using age, BMI, urinary sodium, calcium, oxalate, and
      uric acid as variables. CONCLUSION: Distinguishing uric acid from calcium oxalate
      stones can be performed with relative accuracy using parameters from the 24-hour
      urine stone risk profile and the patient's BMI and age.

PMID- 24460028
TI  - The presence of an air-water interface affects formation and elongation of alpha
      Synuclein fibrils.
AB  - The aggregation of human alpha-Synuclein (alpha-Syn) into amyloid fibrils is
      related to the onset of multiple diseases termed synucleinopathies. Substantial
      evidence suggests that hydrophobic-hydrophilic interfaces promote the aggregation
      of amyloidogenic proteins and peptides in vitro. In this work the effect of the
      air-water interface (AWI) on alpha-Syn aggregation is investigated by means of
      thioflavin T binding measurements, dynamic light scattering, size-exclusion
      chromatography, electron microscopy, and atomic force microscopy. Measurements
      were performed with the monomeric protein alone or together with preformed seeds.
      In presence of the AWI, alpha-Syn aggregates readily into amyloid fibrils that
      remain adsorbed to the AWI. Instead, when the AWI is removed from the samples by
      replacing it with a solid-liquid interface, the interfacial aggregation of
      monomeric alpha-Syn is greatly reduced and no significant increase in ThT
      fluorescence is detected in the bulk, even at 900 MUM concentration. Bulk
      aggregation is observed only when a sufficient amount of preformed seeds is
      added, and the initial slope of the kinetics scales with the amount of seeds as
      expected for first order kinetics. By contrast, in seeded experiments with the
      AWI, the initial slope is one order of magnitude lower and secondary nucleation
      pathways appear instead to be dominant. Thus, interfaces play multiple roles in
      the aggregation of alpha-Syn, influencing primary nucleation, aggregate
      elongation, and secondary nucleation processes. Interfacial effects must
      therefore be taken into account to achieve a complete understanding of protein
      aggregation events in vitro as well as in vivo. 

PMID- 24460027
TI  - Suppression of neovascularization of donor corneas by transduction with equine
      infectious anemia virus-based lentiviral vectors expressing endostatin and
      angiostatin.
AB  - Corneal transplantation is the oldest and one of the most successful transplant
      procedures with a success rate in many studies in excess of 90%. The high success
      rate is mainly attributable to the relatively immune-privileged status of the eye
      and the fact that the cornea is largely avascular. However, the success rate in
      patients with failed grafts is much lower such that regrafting is frequently the
      top indication for corneal transplantation in many centers. Neovascularization is
      the most important risk factor for rejection, as it allows access of the immune
      system to the donor tissue, compromising immune privilege of the graft/eye. We
      have developed a process to modify donor corneal tissue to prevent rejection by a
      single exposure to a gene therapy vector before surgery (EncorStat((r))). The
      vector used is based on clinically relevant equine infectious anemia virus (EIAV)
      derived lentiviral platform and contains genes for two potently angiostatic
      genes, endostatin and angiostatin. We show that incubation of rabbit, primate,
      and human corneal tissue with the EIAV vector mediates strong, stable expression
      in the corneal endothelium. We have optimized this process to maximize
      transduction and, once this is complete, maximize the removal of free vector
      before transplant. Rabbit corneas treated with two different antiangiogenic
      expression vectors (EIAV-EndoAngio and to a lesser extent EIAV-Endo:k5)
      significantly suppressed neovascularization in a rabbit model of corneal
      rejection. As a result, corneal opacity, edema, and inflammatory infiltrates were
      reduced in these corneas. This study demonstrates that angiogenesis is a suitable
      target to prevent corneal rejection, and provides the first proof-of-concept data
      for the development of EncorStat, an ex vivo gene therapy treatment to prevent
      corneal rejection.

PMID- 24460029
TI  - Impact of glutathione-enriched inactive dry yeast preparations on the stability
      of terpenes during model wine aging.
AB  - The impact of the addition of glutathione-enriched Inactive dry yeast
      preparations (g-IDYs) on the stability of some typical wine terpenes (linalool,
      alpha-terpineol, beta-citronellol, and nerol) stored under accelerated oxidative
      conditions was evaluated in model wines. Additionally, the effects of a second
      type of IDY preparation with a different claim (fermentative nutrient) and the
      sole addition of commercial glutathione into the model wines were also assessed.
      Model wines were spiked with the low molecular weight fraction (<3 kDa permeate)
      isolated from the IDYs, avoiding the interaction of aroma compounds with other
      yeast components. An exhaustive chemical characterization of both IDY permeates
      was carried out by using targeted and nontargeted metabolomics approaches using
      CE-MS and FT-ICR-MS analytical platforms. The findings suggest that the addition
      of <3 kDa permeate isolated from any of the IDYs employed decreases the loss of
      typical wine terpenes in model wines submitted to accelerated aging conditions.
      The g-IDY preparation did indeed release reduced GSH into the model wines,
      although this compound did not seem exclusively related to the protective effect
      on some aroma compounds determined in both model wines. The presence of other
      sulfur-containing compounds from yeast origin in g-IDY, and also the presence of
      small yeast peptides, such as methionine/tryptophan/tyrosine-containing
      tripeptide in both types of IDYs, seemed to be related to the antioxidant
      activity determined in the two permeates and to the minor loss of some terpenes
      in the model wines spiked with them. 

PMID- 24460030
TI  - Anisotropic local physical properties of human dental enamel in comparison to
      properties of some common dental filling materials.
AB  - OBJECTIVE: A major aspect in evaluating the quality of dental materials is their
      physical properties. Their properties should be a best fit of the ones of dental
      hard tissues. Manufacturers give data sheets for each material. The properties
      listed are characterized by a specific value. This assumes (but does not prove)
      that there is no direction dependence of the properties. However, dental enamel
      has direction-dependent properties which additionally vary with location in the
      tooth. The aim of this paper is to show the local direction dependence of
      physical properties like the elastic modulus or the thermal expansion in dental
      hard tissues. With this knowledge the 'perfect filling/dental material' could be
      characterized. MATERIALS AND METHOD: Enamel sections of ~400-500 MUm thickness
      have been cut with a diamond saw from labial/buccal to palatal/lingual (canine,
      premolar and molar) and parallel to labial (incisor). Crystallite arrangements
      have been measured in over 400 data points on all types of teeth with x-ray
      scattering techniques, known from materials science. RESULTS: X-ray scattering
      measurements show impressively that dental enamel has a strong direction
      dependence of its physical properties which also varies with location within the
      tooth. Dental materials possess only little or no property direction dependence.
      Therefore, a mismatch was found between enamel and dental materials properties.
      CONCLUSION: Since dental materials should possess equal (direction depending)
      properties, worthwhile properties could be characterized by transferring the
      directional properties of enamel into a property 'wish list' which future dental
      materials should fulfil. Hereby the 'perfect dental material' can be
      characterized.

PMID- 24460031
TI  - A multivariable analysis of patient dental satisfaction and oral health-related
      quality-of-life. A cross-sectional study based on DVSS and OHIP-14.
AB  - OBJECTIVE: The aim of this paper was to study the association between dental
      satisfaction and oral health-related quality-of-life (OHRQoL) when controlling
      for individual, clinical and psychological factors. MATERIALS: Secondary analysis
      was conducted using data from a large study carried out in the Swedish region of
      Varmland in 2004. The questionnaire included demographic variables, clinical
      assessment and the following instruments: the Dental Visit Satisfaction Scale
      (DVSS), the short version of Oral Health Impact Profile (OHIP-14) and a modified
      version of the revised helping alliance questionnaire. Internal consistency
      analysis was undertaken on the instruments to assess reliability; bivariate
      comparisons were assessed to compare DVSS scores with individual factors (age,
      gender and education). In addition, a three step hierarchical multiple regression
      analysis was performed with DVSS as a dependent variable. RESULTS: Data were
      completed for 485 randomly selected patients. The mean age of participants was
      43.5 years, 54.6% were women,and 41.2% had high education. The median DVSS score
      was 48 (range 10-50) and the median OHIP was 3.0 (range 0-56). All the
      instruments showed good reliability. Bivariate analysis showed that females were
      more satisfied than males (p <= 0.01) and patients of 50 years or older were more
      satisfied than the younger ones (p <= 0.05). Finally, the following variables
      explained 31% of the variance of being very satisfied with dental visit: a good
      OHRQoL and patients' positive perceptions of the relationship with their care
      provider. CONCLUSION: This study showed positive associations between dental
      satisfaction and OHRQoL when controlling for related factors. The result suggests
      that care providers should take into account the various dimensions of OHRQoL
      rather than use only clinical measurements when they evaluate patient
      satisfaction.

PMID- 24460032
TI  - Effects of resveratrol and irradiation upon oral squamous cell carcinoma cells.
AB  - OBJECTIVE: To evaluate the effects of resveratrol and irradiation on oral
      squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Resveratrol was
      administered at doses of 5, 10, 25, 50 and 100 uM to PE/CA-PJ15 (OSCC) cultures
      irradiated with different doses (1, 2.5 and 5 Gy). Effects upon cell viability,
      apoptosis and migration were evaluated after 24, 48 and 72 h incubation. RESULTS:
      After 72 h of incubation, the 100 uM dose of resveratrol induced the greatest
      decrease in cell viability at all irradiation doses. After 24, 48 and 72 h of
      incubation, 100 uM of resveratrol induced the greatest cell apoptosis at all
      irradiation doses. The greatest alterations in the distribution of the G0-G1, G2
      M and S phases of the cell cycle were recorded with 50 and 100 uM of resveratrol;
      after 24, 48 and 72 h of incubation, both these doses resulted in an increase in
      the S phase, at the expense of the G0-G1 and G2-M phases. CONCLUSIONS:
      Resveratrol increases cytotoxic activity in the PE/CA-PJ15 cell line and reduces
      cell migration capacity, while the combination of resveratrol and irradiation
      exerts a synergic effect.

PMID- 24460033
TI  - Efficacy of a 10% chlorhexidine coating to prevent caries in at-risk community
      dwelling adults.
AB  - OBJECTIVE: The purpose of the study was to determine the efficacy of a 10%
      chlorhexidine tooth coating in reducing the incidence of cavitated carious
      lesions in adults. MATERIALS AND METHODS: The trial was a randomized, double
      blind, multi-center, placebo controlled study with 983 participants, receiving
      the application of either the active or the placebo coatings to the entire
      dentition. Four applications were made in the first month and one at the 7th
      month. The final examination was performed at 13 months. RESULTS: Coronal caries
      showed a statistical reduction (p = 0.02). Examination of the results by site
      showed that the highest risk participants experienced the most significant
      preventive effect (p = 0.003). When two sites (uninsured and public health) are
      pooled the treatment p-value is 0.0009, interaction term has a p-value of 0.0001.
      CONCLUSION: 10% Chlorhexidine was highly effective in high risk participants with
      more than two cavities at the initial examination. This trial in conjunction with
      other published trials of this topical medication indicates that chlorhexidine
      exerts its action by preventing the transition of D1 lesions to cavitated
      lesions, not on sound to D1 lesions.

PMID- 24460034
TI  - Impact of low birthweight on early childhood caries in 6-36 months old infants in
      Uganda: A cross-sectional study.
AB  - OBJECTIVE: Focusing on 6-36 months old infants, this study assessed (1) whether
      socio-economic status, current anthropometric status, presence of enamel
      hypoplasia, number of erupted teeth, oral hygiene and consumption of sugared
      snacks varied between children with normal birthweight (NBW) and low birthweight
      (LBW) and (2) the association between ECC and birthweight whilst adjusting for
      covariates of ECC, such as current anthropometric status. METHOD: A cross
      sectional study was conducted in Kampala in 2007, involving 816 child/caretaker
      pairs. All caretakers completed face-to-face interviews. Children were examined
      for ECC and enamel defects using WHO (1997) criteria and the developmental
      defects of enamel (DDE) index. Weight at birth was obtained from hospital records
      and current anthropometric status was assessed using z-scores for weight-for
      length (WLZ), length-for-age (LAZ) and weight-for-age (WAZ). RESULTS: Prevalence
      of LBW (< 2500 g) and ECC were estimated to 11.5% and 18.1%, respectively.
      Children with LBW and those with ECC presented with more visible plaque, higher
      sugar consumption and more current underweight (WAZ < -2) than children with
      normal birth weight (NBW) and no caries; 26.7% of LBW vs 17.3% (p < 0.001) of NBW
      children presented with ECC. Enamel defects (OR = 2.8, 95% CI = 1.6-4.8) and
      presence of visible plaque (OR = 2.4, 95% CI = 1.3-4.1), but not LBW, were
      associated with ECC in multiple variable logistic regression analyses.
      CONCLUSION: Both LBW and ECC were associated with poor oral hygiene, high intake
      of sugars and current underweight. Enamel defects were associated with ECC.
      Adjusting for covariates there were no clear association between LBW and ECC.
      Studies using a prospective study design are needed for further investigation.

PMID- 24460035
TI  - Polarity controlled reaction path and kinetics of thermal cis-to-trans
      isomerization of 4-aminoazobenzene.
AB  - Spectral and kinetic behavior of thermal cis-to-trans isomerization of 4
      aminoazobenzene (AAB) is examined in various solvents of different polarities. In
      contrast to azobenzene (AB), it is found the rate of thermal isomerization of AAB
      is highly dependent on solvent polarity. Accelerated rates are observed in polar
      solvents as compared to nonpolar solvents. Moreover, a decrease in the barrier
      height with an increase in medium polarity is observed. Our observations suggest
      that inversion is the preferred pathway in cis-to-trans thermal isomerization in
      a nonpolar medium; however, in a polar medium, the isomerization path deviates
      from the inversion route and rotational behavior is incorporated. Differences in
      the kinetics and in mechanisms of isomerization in different media are
      rationalized in terms of modulation in barrier height by polarity of the medium
      and solute-solvent interaction. It is found that kinetics as well as the
      mechanism of thermal isomerization in AAB is controlled by the polarity of the
      medium. 

PMID- 24460038
TI  - Processes of zinc attenuation by biogenic manganese oxides forming in the
      hyporheic zone of Pinal Creek, Arizona.
AB  - The distribution and speciation of Zn sorbed to biogenic Mn oxides forming in the
      hyporheic zone of Pinal Creek, AZ, was investigated using extended X-ray
      absorption fine structure (EXAFS) and microfocused synchrotron X-ray fluorescence
      (MUSXRF) mapping, and chemical extraction. MUSXRF and chemical extractions show
      that contaminant Zn co-varied with Mn in streambed sediment grain coatings. Bulk
      and microfocused EXAFS spectra of Zn in the biogenic Mn oxide coating are
      indicative of Zn forming triple-corner-sharing inner-sphere complexes over
      octahedral vacancies in the Mn oxide sheet structure. Zn desorbed in response to
      the decrease in pH in batch experiments and resulted in near-equal dissolved Zn
      at each pH over a 10-fold range in the solid/solution ratio. The geometry of
      sorbed Zn was unchanged after 50% desorption at pH 5, indicating that desorption
      is not controlled by dissolution of secondary Zn phases. In summary, these
      findings support the idea that Zn attenuation in Pinal Creek is largely
      controlled by sorption to microbial Mn oxides forming in the streambed during
      hyporheic exchange. Sorption to biogenic Mn oxides is likely an important process
      of Zn attenuation in circum-neutral pH reaches of many acid-mine drainage
      contaminated streams when dissolved Mn is present. 

PMID- 24460039
TI  - In situ separation and collection of oil from water surface via a novel
      superoleophilic and superhydrophobic oil containment boom.
AB  - We have prepared a porous, superoleophilic and superhydrophobic miniature oil
      containment boom (MOCB) for the in situ separation and collection of oils from
      the surface of water. The MOCB was fabricated by a one-step electrodepositing of
      Cu2O film on Cu mesh surface without using low surface energy materials. Oils on
      water surface could be fast contained in the MOCB while water was completely
      repelled out of the MOCB, thus achieving the separation of oil from water
      surface. In addition, the contained oil in the MOCB could be in situ collected
      easily by a dropper, thus achieving the collection of oil. Moreover, the MOCB
      could be reused for many times in the oil-water separating process with large
      separation abilities more than 90%. The MOCB also possessed excellent water
      pressure resistance for about 164 mm water column and good corrosion resistance
      in simulating seawater. Therefore, the findings in the present study might offer
      a simple, fast, and low-cost method for the in situ separation and collection of
      oil spills on seawater surface. 

PMID- 24460036
TI  - Factors related to the sensitivity of emergency medical service impression of
      stroke.
AB  - OBJECTIVES: To examine factors related to sensitivity of emergency medical
      services (EMS) stroke impression. METHODS: We reviewed ambulance and hospital
      records of all patients transported to Long Island College Hospital between
      January 1, 2009 and January 1, 2011 by the hospital-based EMS with a discharge
      diagnosis of stroke or a confounding diagnosis, and compared EMS impression to
      hospital discharge diagnosis. We examined relationships between EMS diagnostic
      sensitivity and age, gender, ethnicity, NIH Stroke Scale (NIHSS), motor signs,
      aphasia, neglect, lesion side, circulation, stroke type, EMS provider level, and
      documented Cincinnati Pre-hospital Stroke Scale (CPSS) with contingency analysis
      and logistic regression. RESULTS: Stroke was validated in 18% (56/310) of
      patients and 50% (28/56) of these were missed by EMS. EMS diagnostic sensitivity
      was 50% (95% CI: 36-64%), and was related to NIHSS quartile (p = 0.014), with
      higher sensitivities in 2nd (69%; 95% CI: 44-86%) and 3rd (75%; 95% CI: 47-91%)
      vs. 1st (20%; 95% CI: 7-45%) and 4th (45%; 95% CI: 21-72%) quartiles, motor signs
      (62 vs. 14%, p = 0.002), and documented CPSS (84 vs. 32%, p = 0.0002). EMS
      impression was independently related to NIHSS quartile (1st vs. 2nd adjusted OR =
      9.61, 1.13-122.03, p = 0.038) and CPSS (adjusted OR = 12.58, 2.22-111.06, p =
      0.003). CONCLUSION: Stroke was missed more frequently when CPSS was not
      documented, in patients without motor signs, and in patients with moderate-severe
      stroke. The sensitivity of prehospital screening for patients with moderate
      severe stroke might be improved by including additional non-motor signs and by
      stressing indications for when screens should be performed.

PMID- 24460041
TI  - Comparison of single cone obturation performance of different novel nickel
      titanium rotary systems.
AB  - OBJECTIVES: The purpose of this study was to compare several different single
      cone obturations in the gutta-percha-filled areas (PGFA), sealer-filled areas
      (PSFA) and voids, also determining the volumetric characteristics of the tested
      cones. MATERIALS AND METHODS: Curved mesial roots of 120 mandibular molars were
      instrumented using several different systems (ProTaper Next, Twisted File
      Adaptive, OneShape, ProTaper Universal, WaveOne and Reciproc) and filled with
      corresponding single cones. The teeth were then sectioned horizontally at 2, 4, 6
      and 8 mm from the apex. The area values of each section were calculated and
      converted to percentages (PGFA, PSFA and voids) of the total area. To determine
      volumetric characteristics of the tested cones, 20 gutta-percha points of each
      tested group were scanned with CBCT using the same parameters. RESULTS: The
      ProTaper Next and WaveOne groups presented the most PGFA and least PSFA. The
      Twisted File Adaptive group presented the least PGFA and most PSFA (p < 0.05) and
      the least gutta-percha volume. CONCLUSIONS: The Twisted File Adaptive system
      matched cones had the least volume and the least PGFA in severely curved
      mesiobuccal canals of mandibular first molars. Single matched cones volume
      varied.

PMID- 24460042
TI  - Differential influence of fluoride concentration on the synthesis of bone matrix
      glycoproteins within mineralizing bone cells in vitro.
AB  - OBJECTIVE: This study investigated the influence of fluoride levels on the
      temporal synthesis of bone-associated glycoproteins, which have been assigned
      prominent roles in regulating crystal growth, size and shape during the
      mineralization process. MATERIALS AND METHODS: Bone marrow stromal cells were
      isolated from male Wistar rats and cultured under mineralizing conditions,
      supplemented with 0 M, 10(-7) M or 10(-5) M sodium fluoride. The presence of bone
      associated glycoproteins was examined 2-13 days post-reseeding by
      immunocytochemical localization. Results: All bone-associated glycoproteins
      increased in 10(-7) M fluoride, compared to untreated controls, particularly at
      days 6 and 13 in culture. Conversely, higher 10(-5) M fluoride concentrations
      decreased glycoprotein levels, compared to controls. CONCLUSIONS: Results
      highlight a differential effect of fluoride concentration on glycoprotein
      synthesis by osteoblasts.

PMID- 24460043
TI  - Synthesis of 1-O-methylchlorogenic acid: reassignment of structure for MCGA3
      isolated from bamboo (Phyllostachys edulis) leaves.
AB  - The first synthesis of 1-O-methylchlorogenic acid is described. The short and
      efficient synthesis of this compound provides laboratory-scale quantities of the
      material to investigate its biological properties. The synthesis involves C-1
      alkylation of the known (-)-4,5-cyclohexylidenequinic acid lactone followed by
      methoxide opening to the hydroxyl ester. Acylation of the C-5 hydroxyl group
      followed by sequential removal of protecting groups afforded 1-O
      methylchlorogenic acid. The NMR spectroscopic characteristics of this compound do
      not coincide with those reported for the original isolation from bamboo
      (Phyllostachys edulis) leaves of the compound designated MCGA3. Comparison of the
      published spectroscopic data reported for MCGA3, with both reported literature
      values and spectroscopic data obtained from an authentic sample, leads to the
      conclusion that the compound isolated from bamboo (Phyllostachys edulis) leaves
      is instead methyl chlorogenate. 

PMID- 24460044
TI  - Differentiation and the least common denominator.

PMID- 24460046
TI  - Experimental and computational investigation of the patient-specific abdominal
      aortic aneurysm pressure field.
AB  - The objective of the present manuscript is three-fold: (i) to study the detailed
      pressure field inside a patient-specific abdominal aortic aneurysm (AAA) model
      experimentally and numerically and discuss its clinical relevance, (ii) to
      validate a number of possible numerical model options and their ability to
      predict the experimental pressure field and (iii) to compare the spatial pressure
      drop in the AAA before and after the formation of intraluminal thrombus (ILT) for
      a late disease development timeline. A finite volume method was used to solve the
      governing equations of fluid flow to simulate the flow dynamics in a numerical
      model of the AAA. Following our patient-specific anatomical rapid prototyping
      technique, physical models of the aneurysm were created with seven ports for
      pressure measurement along the blood flow path. A flow loop operating with a
      blood analogue fluid was used to replicate the patient-specific flow conditions,
      acquired with phase-contrast magnetic resonance imaging, and measure pressure in
      the flow model. The Navier-Stokes equations and two turbulent models were
      implemented numerically to compare the pressure estimations with experimental
      measurements. The relative pressure difference from experiments obtained with the
      best performing model (unsteady laminar simulation) was ~1.1% for the AAA model
      without ILT and ~15.4% for the AAA model with ILT (using Reynolds Stress Model).
      Future investigations should include validation of the 3D velocity field and wall
      shear stresses within the AAA sac predicted by the three numerical models.

PMID- 24460045
TI  - The perception of prosody and associated auditory cues in early-implanted
      children: the role of auditory working memory and musical activities.
AB  - OBJECTIVE: To study prosodic perception in early-implanted children in relation
      to auditory discrimination, auditory working memory, and exposure to music.
      DESIGN: Word and sentence stress perception, discrimination of fundamental
      frequency (F0), intensity and duration, and forward digit span were measured
      twice over approximately 16 months. Musical activities were assessed by
      questionnaire. STUDY SAMPLE: Twenty-one early-implanted and age-matched normal
      hearing (NH) children (4-13 years). RESULTS: Children with cochlear implants
      (CIs) exposed to music performed better than others in stress perception and F0
      discrimination. Only this subgroup of implanted children improved with age in
      word stress perception, intensity discrimination, and improved over time in digit
      span. Prosodic perception, F0 discrimination and forward digit span in implanted
      children exposed to music was equivalent to the NH group, but other implanted
      children performed more poorly. For children with CIs, word stress perception was
      linked to digit span and intensity discrimination: sentence stress perception was
      additionally linked to F0 discrimination. CONCLUSIONS: Prosodic perception in
      children with CIs is linked to auditory working memory and aspects of auditory
      discrimination. Engagement in music was linked to better performance across a
      range of measures, suggesting that music is a valuable tool in the rehabilitation
      of implanted children.

PMID- 24460047
TI  - Lack of genetic susceptibility of KCNJ11 E23K polymorphism with risk of type 2
      diabetes in an Iranian population.
AB  - AIMS: The KCNJ11 gene has a strong effect on glucose-stimulated insulin
      secretion. Common polymorphism KCNJ11 E23K has been reported to be associated
      with type 2 diabetes in various European-descent populations. However, there were
      inconsistent results in previous studies in Asian populations, and no study has
      been carried out in the Iranian population. We examined the contribution of
      KCNJ11 E23K variant in the susceptibility to type 2 diabetes in the Iranian
      population. METHODS: We undertook a population-based association study between
      type 2 diabetes and E23K mutation using 400 people with type 2 diabetes and 420
      controls. Genotyping was performed using TaqMan technology on an ABI7300 system.
      RESULTS: No significant difference was observed in either genotype distribution
      (p = 0.71) or allele frequency (p = 0.88) between individuals with and without
      type 2 diabetes. After adjusting for the confounding effects of age, gender and
      body mass index (BMI), no significant effect of genotypes on type 2 diabetes was
      found regarding any genetic models tested (recessive, dominant or co-dominant
      models). Following subgroup analysis of individuals with and without diabetes
      based on BMI, a nominal significant association was observed between type 2
      diabetes in the presence of obesity and E23K genotype in the recessive model (p =
      0.03). CONCLUSION: The KCNJ11 E23K polymorphism is not associated with genetic
      susceptibility to type 2 diabetes in the Iranian population; however, it may play
      a role in disease progression in the presence of obesity.

PMID- 24460048
TI  - Vibrationally resolved photoelectron imaging of Au3H(-).
AB  - We report a combined photoelectron velocity map imaging spectroscopy and density
      functional theory investigation on the Au3H(-) anion. Transition between the
      anionic electronic ground state and the neutral electronic ground state is
      revealed. Vibrationally resolved spectra were recorded at two different photon
      energies, providing a wealth of spectroscopic information for the electronic
      ground state of the Au3H. Franck-Condon simulations of the ground-state
      transition are carried out to assist in the assignment of the vibrationally
      resolved spectra. The electron affinity and vertical detachment energy of Au3H
      are measured to be 2.548 +/- 0.001 and 2.570 +/- 0.001 eV, respectively. Three
      stretching vibrational modes are determined to be activated upon photodetachment,
      with the frequencies of 2100 +/- 100, 177 +/- 10, and 96 +/- 10 cm(-1). 

PMID- 24460050
TI  - Editorial: Intraoperative neurophysiological monitoring and spinal deformity
      surgery.

PMID- 24460051
TI  - Neuromonitoring changes in pediatric spinal deformity surgery: a single
      institution experience.
AB  - OBJECT: Intraoperative monitoring of the spinal cord has become the standard of
      care during surgery for pediatric spinal deformity correction. The use of both
      somatosensory and motor evoked potentials has dramatically increased the
      sensitivity and specificity of detecting intraoperative neurophysiological
      changes to the spinal cord, which assists in the intraoperative decision-making
      process. The authors report on a large, single-center experience with
      neuromonitoring changes and outline the surgical management of patients who
      experience significant neuromonitoring changes during spinal deformity correction
      surgery. METHODS: The authors conducted a retrospective review of all cases
      involving pediatric patients who underwent spinal deformity correction surgery at
      Shriners Hospital for Children, Philadelphia, between January 2007 and March
      2010. Five hundred nineteen consecutive cases were reviewed in which
      neuromonitoring was used, with 47 cases being identified as having significant
      changes in somatosensory evoked potentials, motor evoked potentials, or both.
      These cases were reviewed for patient demographic data and surgical
      characteristics. RESULTS: The incidence of significant neuromonitoring changes
      was 9.1% (47 of 519 cases), including 6 cases of abnormal Stagnara wake-up tests,
      of which 4 had corroborated postoperative neurological deficits (8.5% of 47
      cases, 0.8% of 519). In response to neuromonitoring changes, wake-up tests were
      performed in 37 (79%) of 47 cases, hardware was adjusted in 15 (32%),
      anesthesiology interventions were reported in 5 (11%), hardware was removed in 5
      (11%), the patient was successfully repositioned in 3 (6%), and the procedure was
      aborted in 13 (28%). In 1 of the 4 patients with new postoperative deficits, the
      deficit had fully resolved by the last follow-up; the other 3 patients had
      persistent neurological impairment as of the most recent follow-up examination.
      The authors observed a sensitivity of 100% for intraoperative neuromonitoring.
      CONCLUSIONS: Due to the profound risks associated with spinal deformity surgery,
      intraoperative neurophysiological monitoring is an integral tool to warn of
      impending spinal cord injury. Intraoperative neuromonitoring appears to provide a
      safe and useful warning mechanism to minimize spinal cord injury that may arise
      during scoliosis correction surgery in pediatric patients.

PMID- 24460052
TI  - Improvement of the cycling performance of LiNi(0.6)Co(0.2)Mn(0.2)O(2) cathode
      active materials by a dual-conductive polymer coating.
AB  - LiNi0.6Co0.2Mn0.2O2 cathode materials were surface-modified by coating with a
      dual conductive poly(3,4-ethylenedioxythiophene)-co-poly(ethylene glycol) (PEDOT
      co-PEG) copolymer, and their resulting electrochemical properties were
      investigated. The surface-modified LiNi0.6Co0.2Mn0.2O2 cathode material exhibited
      a high discharge capacity and good high rate performance due to enhanced
      transport of Li(+) ions as well as electrons. The presence of a protective
      conducting polymer layer formed on the cathode also suppressed the growth of a
      resistive layer and inhibited the dissolution of transition metals from the
      active cathode materials, which resulted in more stable cycling characteristics
      than the pristine LiNi0.6Co0.2Mn0.2O2 cathode material at 55 (o)C. 

PMID- 24460055
TI  - Influence of the boron precursor and drying method on surface properties and
      electrochemical behavior of boron-doped carbon gels.
AB  - Two series of B-doped carbon gels were prepared by the polymerization of
      resorcinol and formaldehyde in water using either boric acid or phenyl boronic
      acid as dopants. Both organic hydrogels were dried by four methods:
      supercritical, freeze, microwave oven, and vacuum oven drying. The effects of the
      boron precursor and drying method on the surface characteristics were studied by
      N2 and CO2 adsorption at -196 and 0  degrees C, respectively, immersion
      calorimetry into benzene and water, temperature-programmed desorption coupled
      with mass spectrometry, X-ray photoelectron spectroscopy, and thermogravimetric
      analysis. Electrochemical characterization was carried out in a three-electrode
      cell, using Ag/AgCl as a reference electrode and a Pt wire as a counter
      electrode. The surface area obtained from immersion calorimetry into benzene was
      more realistic than that yielded by the Brunauer-Emmett-Teller (BET) equation.
      The hydrophobicity of the samples decreased linearly with a higher oxygen
      content. In addition, the oxygen content of the B-doped carbon gels increased
      linearly with a higher B content, and the interfacial or areal capacitance
      decreased linearly with a larger surface area. The capacitance was increased by B
      addition because of the pseudocapacitance effects of the higher oxygen content of
      the samples. The cryogel and vacuum-dried xerogel obtained from the boric acid
      series, Bc and Bv, respectively, showed the largest gravimetric and volumetric
      capacitances, around 140 F/g and 95 F/cm(3), respectively. 

PMID- 24460056
TI  - Phase behavior and relative stability of malonamide polymorphs.
AB  - The three known polymorphs of malonamide have been characterized by thermal
      analysis and X-ray powder diffraction. The melting thermodynamic characteristics
      of the three forms are thus proposed in the present paper. From these data, the
      relative thermodynamic stability of these three solid forms has been determined.
      It appears that an enantiotropic behavior is established between the monoclinic
      and the orthorhombic phases while the quadratic one is monotropic with respect to
      the other two. 

PMID- 24460057
TI  - Unequal partnership: asymmetric roles of polymeric donor and fullerene acceptor
      in generating free charge.
AB  - Natural photosynthetic complexes accomplish the rapid conversion of
      photoexcitations into spatially separated electrons and holes through precise
      hierarchical ordering of chromophores and redox centers. In contrast, organic
      photovoltaic (OPV) cells are poorly ordered, utilize only two different chemical
      potentials, and the same materials that absorb light must also transport charge;
      yet, some OPV blends achieve near-perfect quantum efficiency. Here we perform
      electronic structure calculations on large clusters of functionalized fullerenes
      of different size and ordering, predicting several features of the charge
      generation process, outside the framework of conventional theories but clearly
      observed in ultrafast electro-optical experiments described herein. We show that
      it is the resonant coupling of photogenerated singlet excitons to a high-energy
      manifold of fullerene electronic states that enables efficient charge generation,
      bypassing localized charge-transfer states. In contrast to conventional views,
      our findings suggest that fullerene cluster size, concentration, and
      dimensionality control charge generation efficiency, independent of exciton
      delocalization. 

PMID- 24460058
TI  - Literacy skills of Australian Indigenous school children with and without otitis
      media and hearing loss.
AB  - This study examined the relationship between reading, spelling, and the presence
      of otitis media (OM) and co-occurring hearing loss (HL) in metropolitan
      Indigenous Australian children, and compared their reading and spelling outcomes
      with those of their non-Indigenous peers. OM and HL may hinder language
      development and phonological awareness skills, but there is little empirical
      evidence to link OM/HL and literacy in this population. Eighty-six Indigenous and
      non-Indigenous children attending pre-primary, year one and year two at primary
      schools in the Perth metropolitan area participated in the study. The ear health
      of the participants was screened by Telethon Speech and Hearing Centre EarBus in
      2011/2012. Participants' reading and spelling skills were tested with culturally
      modified sub-tests of the Queensland University Inventory of Literacy. Of the 46
      Indigenous children, 18 presented with at least one episode of OM and one episode
      of HL. Results indicated that Indigenous participants had significantly poorer
      non-word and real word reading and spelling skills than their non-Indigenous
      peers. There was no significant difference between the groups of Indigenous
      participants with OM and HL and those with normal ear health on either measure.
      This research provides evidence to suggest that Indigenous children have ongoing
      literacy development difficulties and discusses the possibility of OM as one of
      many impacting factors.

PMID- 24460059
TI  - Interpreting the rich behavior of ternary DNA-PEI-Fe(III) complexes.
AB  - This work aims to shed light on the mechanism of interaction between components
      of ternary DNA-PEI-Fe(III) complexes, using experimental and theoretical
      approaches. In the experimental part, the chelation between PEI-Fe(III) was
      inspected by potentiometry and electrical conductance measurements and the
      respective importance for the condensation of DNA analyzed. To this end, three
      different mixing protocols for the components were imposed using different PEIs,
      branched (bPEI1.2 and bPEI10) and linear (lPEI2.5 and lPEI25). A delay in DNA
      condensation was observed when PEI and Fe(III) were premixed and then added to
      DNA. The set of observations was complemented by determination of the amount of
      Fe(III) included in the polyplexes, which was found to be dependent on the order
      of mixture and on the type of PEI used, decreasing with intrinsic PEI
      condensation efficiency. Overall, a coherent picture in which Fe(III) compensates
      PEI, probably modulating the respective charge, emerges. Some points arisen from
      the experimental part were rationalized using Monte Carlo simulations. Different
      architectured polycation (PC) chains were modeled and an interaction between PC
      and multivalent ions, mimicking the chelation of Fe(III) by the PEI, was imposed.
      It was found that chelation enhances polyanion (PA) compaction, irrespective of
      the PC architecture and charge density. The amount of multivalent ions in each
      polyplex compensates the negative charge unbalanced by the PC. The charge density
      and the ability of chelation of each PC dictate the disposition of each
      condensing agent along the PA backbone, and their coexistence strengthens PA
      compaction. The deep understanding of these ternary mixtures is a step forward in
      the optimization of such systems for application in gene delivery. 

PMID- 24460061
TI  - Arsenate-ferrihydrite systems from minutes to months: a macroscopic and ir
      spectroscopic study of an elusive equilibrium.
AB  - Sorption by ferrihydrite is an important control on As(V) concentrations in many
      oxic aquatic systems. There are significant discrepancies in reported sorption
      constants (log(KAs)), which presents a problem for quantifying and understanding
      this important system. A review of reported ferrihydrite-As(V) sorption studies
      indicated a positive correlation between reaction time used in the experiments
      and the log(KAs) values derived from the data. In this paper, we study the
      kinetics of As(V) sorption over ~3000 h in nine systems with varying pH and
      As(V)/Fe. Ferrihydrite was stable in all systems containing As(V), and the
      [As(V)] in solution decreased linearly as a function of log(t) (termed Elovich
      kinetics) over the full 3000 h in most systems. A stable [As(V)] was only
      observed in systems with low As(V)/Fe and low pH. Apparent As(V) sorption
      constants were derived from the data at specific time intervals using the diffuse
      layer model and equations describing log(KAs) values as a function of time
      provide a way to describe this elusive equilibrium. IR spectra support the
      hypothesis that slow interparticle diffusion is responsible for the slow approach
      to equilibrium. This work resolves discrepancies in previous studies of As(V)
      ferrihydrite and provides equations to allow for system appropriate log(KAs)
      values to be used. 

PMID- 24460062
TI  - Response to Dr. Dobie's letter to the editor titled "Comments re Macrae (2013)".

PMID- 24460064
TI  - Mutagenesis breeding for increased 3-deoxyanthocyanidin accumulation in leaves of
      Sorghum bicolor (L.) Moench: a source of natural food pigment.
AB  - Natural food colorants with functional properties are of increasing interest.
      Prior papers indicate the chemical suitability of sorghum leaf 3
      deoxyanthocyanidins as natural food colorants. Via mutagenesis-assisted breeding,
      a sorghum variety that greatly overaccumulates 3-deoxyanthocyanidins of leaf
      tissue, named REDforGREEN (RG), has been isolated and characterized.
      Interestingly, RG not only caused increased 3-deoxyanthocyanidins but also caused
      increased tannins, chlorogenic acid, and total phenolics in the leaf tissue.
      Chemical composition of pigments was established through high-performance liquid
      chromatography (HPLC) that identified luteolinidin (LUT) and apigeninidin (APG)
      as the main 3-deoxyanthocianidin species. Specifically, 3-deoxyanthocianidin
      levels were 1768 MUg g-1 LUT and 421 MUg g-1 APG in RG leaves compared with trace
      amounts in wild type, representing 1000-fold greater levels in the mutant leaves.
      Thus, RG represents a useful sorghum mutagenesis variant to develop as a
      functionalized food colorant.

PMID- 24460065
TI  - Both gender and concurrent chronic lymphocytic thyroiditis may influence the
      nuclear texture of papillary thyroid carcinomas cells.
AB  - A disparity in gender incidence has been reported in both papillary thyroid
      carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) diseases frequently
      associated and whose incidence has been increasing in parallel. We aimed to
      analyze differences in morphometric variables between male and female PTC
      patients and their relationship with the presence of concurrent CLT. The nuclear
      texture features of 100 hematoxylin-eosin stained nuclei from 100 consecutive
      classic PTC patients enrolled in our service were compared with their clinical
      and pathological features, including the presence of CLT. All patients were
      submitted to a standard management protocol and followed-up for 13-248 months (Mo
      = 117 months). Chromatin in women tended to present a denser and more homogeneous
      structure, in a less mottled pattern, with higher values of energy (p = 0.008)
      and diagonal moment (p = 0.032) than men. Concurrent CLT was more prevalent in
      women (41.42%) than in men (13.33%, p = 0.04) and was associated with higher
      cluster prominence values (p = 0.027), a parameter that indicates a predominance
      of high nuclear contrasted heterochromatin. A multivariate logistic regression
      analysis showed that higher cluster prominence was independently correlated with
      chromatin in patients who presented CLT but did not demonstrate any association
      between concurrent CLT and gender. We were unable to demonstrate any association
      between gender and any characteristic of tumor aggressiveness or patients
      outcome. Our results suggest that chromatin texture of hematoxylin-eosin stained
      nuclei in paraffin sections of PTC cells is related to both gender and concurrent
      CLT.

PMID- 24460066
TI  - Thermal processing of formamide ices on silicate grain analogue.
AB  - Fourier transform-infrared spectroscopy (FT-IR) and temperature programmed
      desorption (TPD) have been used to examine the thermal processing of three
      isotopes of pure formamide ice (HCONH2, DCONH2, and HCOND2) adsorbed on a SiO2
      interstellar grain analogue. Pure formamide ice on SiO2 nanoparticles displays at
      least three different phases that we interpret as a porous phase from ~70-145 K,
      a compacted polycrystalline phase from ~145-210 K, and a third slow diffusion and
      sublimation phase from ~210-380 K. Possible dimerization is also discussed.
      Formamide desorption from the SiO2 grain surface is characterized by TPD of pure
      HCONH2 and mixed H2O:HCONH2 ices. Water desorbs at 160 K, and formamide has a TPD
      peak maximum at ~228 K. A mean Eact of ~14.7 kcal/mol (0.64 eV) was obtained
      using Redhead analysis, indicating strong intermolecular forces within formamide
      ice. The mixed H2O:HCONH2 ice TPD data suggests possible formamide accumulation
      if the grains are exposed to temperature cycles <180 K. 

PMID- 24460067
TI  - Laparoscopic partial nephrectomy with diode laser: a promising technique.
AB  - OBJECTIVE: The aim of this study was to evaluate application of diode laser in
      laparoscopic partial nephrectomy (LPN), and to question this technique in terms
      of ease of tumor excision and reduction of warm ischemia time (WIT). BACKGROUND
      DATA: LPN is the standard operative method for small renal masses. The benefits
      of LPN are numerous, including preserving renal function and prolonging overall
      survival. However, reduction of WIT remains main challenge in this operation. In
      order to shorten WIT, many techniques have been developed, with variable results.
      PATIENTS AND METHODS: We performed a prospective collection and analysis of
      health records for patients who were operated on between March 2011 and August
      2012. Inclusion criteria were single tumor <= 4 cm, predominant exophytic growth
      and intraparenchymal depth <= 1.5 cm, with a minimum distance of 5 mm from the
      urinary collecting system. RESULTS: We operated on 17 patients. Median operative
      time was 170 min. In all but two patients, we had to perform hilar clamping.
      Median duration of WIT was 16 min. Pathohistological evaluation revealed clear
      cell renal cancer and confirmed margins negative for tumor in all cases. Median
      size of the tumor was 3 cm. Median postoperative hospitalization was 5 days.
      Average follow up was 11.5 months. There were no intraoperative complications.
      One postoperative complication was noted: perirenal hematoma. CONCLUSIONS: Laser
      LPN is feasible, and offers the benefit of shorter WIT, with effective tissue
      coagulation and hemostasis. With operative experience and technical advances, WIT
      will be reduced or even eliminated, and a solution to some technical
      difficulties, such as significant smoke production, will be found.

PMID- 24460068
TI  - Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort
      study of 16 928 women 48 years and older.
AB  - BACKGROUND: Findings on potential interactive effects of oral contraceptives
      (OCs) and hormone replacement therapy (HRT) on breast cancer risk have been
      inconsistent. We aimed to use population-based cohort data to determine whether
      former use of OCs affects breast cancer risk among HRT users, taking into account
      regimens of HRT, duration and currency of use. METHODS: The cohort consisted of
      16 928 Icelandic women who visited the Icelandic Cancer Detection Clinic in 1979
      2006 and provided information on use of OCs and HRT when they were 48 years or
      older. By record linkage to the Icelandic Cancer Registry, all breast cancer
      diagnosed during follow-up was identified. Using Cox regression, hazard ratios
      (HRs) for breast cancer according to hormone use were estimated, adjusting for
      menstrual and reproductive risk factors. Also, interaction analyses were carried
      out. RESULTS: Breast cancer risk was significantly increased among ever users of
      combined estrogen and progestin (EP-HRT) preparations (HR=2.61; 95% CI 2.00-3.41)
      and not among users of estrogen-only regimens (E-only HRT) (HR=1.13; 95% CI 0.85
      1.49). Ever users of both OCs and HRT had higher breast cancer risk than users of
      only one of the two (HR=2.19; 95% CI 1.67-2.87). After restricting the analysis
      to EP-HRT and focusing on long-term and current use, there was an indication of a
      negative interaction with ever OC use (p=0.06); HR=2.87; 95% CI 1.79-4.60 for
      never OC users and HR=2.24; 95% CI 1.51-3.34 for former OC users. CONCLUSION:
      After taking HRT regimen, duration and currency of use into account, the results
      of our population-based cohort study do not support the notion that former OC use
      increases breast cancer risk among HRT users, on the contrary there was an
      indication of a slightly lower risk in former OC users, restricted to current,
      long-term EP-HRT users.

PMID- 24460069
TI  - A randomized pilot study with daily walking during adjuvant chemotherapy for
      patients with breast and colorectal cancer.
AB  - BACKGROUND: Physical activity during chemotherapy has been shown in several
      studies to reduce fatigue, improve symptoms and impact positively on health
      related quality of life (HRQoL). Challenges associated with intervention studies
      on physical activity during cancer treatment relate to consistent adherence. The
      primary objective was to study feasibility and adherence of physical activity
      intervention among patients with cancer during adjuvant chemotherapy treatment.
      The secondary objective was to investigate the effects of physical activity on
      health aspects, including HRQoL, symptoms and surrogate markers for
      cardiovascular disease. MATERIAL AND METHODS: This randomized controlled trial
      included patients with breast cancer (BRCA) and colorectal cancer (CRC) during
      adjuvant chemotherapy. The intervention continued for 10 weeks and included daily
      walks of 10 000 steps and a weekly supervised group walk. Adherence was assessed
      by a pedometer and the number of participants who reported step counts every week
      and percentage of participants who achieved the target steps every week. RESULTS:
      Adherence average reached 91% during the intervention period; in total 74%
      completed the exercise intervention. The majority of the participants achieved an
      average of 83% of the target of 10 000 steps per day for 10 weeks. There was a
      significant increase in daily physical activity (p = 0.016) in the intervention
      group. Significant differences were also found for some breast cancer-specific
      symptoms [swelling, mobility and pain (p = 0.045)]. The study showed a relatively
      small weight gain an average of 0.9 kg in the intervention group and 1.3 kg in
      the control group. CONCLUSION: Physical activity in the form of walking is
      feasible during adjuvant chemotherapy treatment despite increasing symptoms. The
      physical activity increased in the intervention group during the study time and
      had a positive impact on breast symptoms and the weight gain was lower in
      comparison to previous studies.

PMID- 24460070
TI  - A method to estimate composite doses for organs at risk in prostate cancer
      patients treated with EBRT in combination with HDR BT.
AB  - BACKGROUND: When evaluating late toxicity after combined external beam radiation
      therapy (EBRT) and high-dose rate brachytherapy (HDR BT) prostate cancer
      treatments, it is important that the composite dose distribution is taken into
      account. This can be challenging if organ-at-risk (OAR) dose data are incomplete,
      i.e. due to a limited ultrasound imaging field-of-view in the HDR BT procedure.
      This work proposes a method that provides estimates of composite OAR doses for
      such situations. MATERIAL AND METHODS: Original EBRT, simulated HDR BT, and
      composite dose-volume histograms (DVHs) for 10 pelvic OARs in 30 prostate cancer
      cases were used for method implementation and evaluation (EBRT: 25*2.0 Gy+BT:
      2*10.0 Gy). The proposed method used information from the EBRT DVH to estimate
      OAR BT doses (with or without fractionation correction). Coefficients of
      determination (R2) were calculated for linear relationships between several EBRT
      DVH parameters and a BT DVH parameter of interest. The largest R2 value decided
      the relationship that best predicted the BT DVH parameter. The composite dose
      value was then calculated by adding the EBRT DVH and the estimated BT DVH
      parameter values and was compared to the reference composite value (in 1200
      OAR/patient/parameter cases). RESULTS: The linear relationships had an average R2
      of 0.68 (range 0.42-0.88). Only one ninth of the 1200 estimated composite DVH
      values differed more than 2 Gy from their reference values. CONCLUSION: Given a
      successful implementation, the proposed method only requires original or
      simulated BT plan data for a subset of patients to estimate composite doses for
      large study populations in a time-efficient manner. This can assist in evaluating
      radiation-induced late toxicity in multimodality treatments with limited OAR dose
      data.

PMID- 24460071
TI  - Does occupational therapy play a role for communication in children with autism
      spectrum disorders?
AB  - This study investigates occupational therapy for early communication in children
      with autism spectrum disorders (ASD). The research explored the role of
      occupational therapists in supporting children with ASD to become better
      communicators by considering their inter-professional collaboration with speech
      language pathologists. Convenience samples of 21 clinical occupational therapists
      and speech-language pathologists were recruited to participate in semi-structured
      audio-recorded focus groups, using a qualitative design. Distinct views included
      a child-centred focus from speech-language pathologists, whereas occupational
      therapists spoke of the child through societal viewpoints, which later pointed to
      occupational therapists' proficiency in enabling skill generalization in ASD. An
      equal partnership was consistently reported between these clinicians, who
      identified the same objectives, shared strategies, joint treatments, and ongoing
      collaboration as the four main facilitators to inter-professional collaboration
      when treating children with ASD. Three unique roles of occupational therapy
      comprised developing non-verbal and verbal communication pre-requisites, adapting
      the setting, educating-partnering-advocating for the child, and providing
      occupation-based intervention. These three themes meshed with the discipline
      specific occupational therapy domains represented in the Person-Environment
      Occupation framework. When working in inter-professional collaboration, speech
      language pathologists and occupational therapists agree that occupational therapy
      is indispensable to early intervention in enabling communication in ASD.

PMID- 24460073
TI  - A numerical study of muco-ciliary transport under the condition of diseased
      cilia.
AB  - Structural and functional disorders of pulmonary cilia may result from genetic
      disorders and acquired insults. A two-dimensional numerical model based on the
      immersed boundary method coupled with the projection method is used to study the
      flow physics of muco-ciliary transport of the human respiratory tract under
      various abnormalities of cilia. The effects of the cilia beat pattern (CBP),
      ciliary length, immotile cilia, beating amplitude and uncoordinated beating of
      cilia are investigated. As expected, the mucus velocity decreases as the beating
      amplitude reduces. The windscreen wiper motion and rigid planar motion, which are
      two abnormal CBPs owing to genetic disorders, greatly reduce or almost stop the
      mucus transport. If the ciliary length varies from its standard length, the mucus
      velocity would decrease. The mucus velocity decreases rather linearly if the
      number of uniformly distributed immotile cilia increases. The numerical results
      show that the mucus velocity would be further reduced marginally when the
      uniformly distributed immotile cilia are rearranged as a cluster of immotile
      cilia. Furthermore, if half of the cilia are immotile and uniformly distributed
      and motile cilia beat at reduced amplitude, the incoordination between the active
      motile cilia would not significantly affect the mucus velocity.

PMID- 24460074
TI  - Simple ligand exchange reactions enabling excellent dispersibility and stability
      of magnetic nanoparticles in polar organic, aromatic, and protic solvents.
AB  - The use of magnetic nanoparticles (MNPs) in real-world applications is often
      limited by the lack of stable solutions of monodisperse NPs in appropriate
      solvents. We report a facile one-pot ligand exchange reaction that is fast,
      efficient, and thorough for the synthesis of hydrophilic MNPs that are readily
      dispersed in polar organic and protic solvents (polarity index = 3.9-7.2)
      including alcohols, THF, DMF, and DMSO for years without precipitation. We
      emphasize the rational selection of small-molecule ligands such as 4
      hydroxybenzoic acid (HBA), 3-(4-hydroxyphenyl)propionic acid (HPP), and gallic
      acid (GAL) that provide strong bonding with the MNP (FePt and FeOx) surfaces,
      hydrophilic termini to match the polarity of target solvents, and offer the
      potential for hydrogen-bonding interactions to facilitate incorporation into
      polymers and other media. Areal ligand densities (Sigma) calculated based on the
      NP core size from transmission electron microscopy (TEM) images, and the
      inorganic fractions of NPs derived from thermogravimetric analysis (TGA)
      indicated a significant (2-4 times) increase in the ligand coverage after the
      exchange reactions. Fourier transform infrared spectrometry (FTIR) and (1)H
      nuclear magnetic resonance (NMR) studies also confirmed anchoring of carboxyl
      groups on NP surfaces. In addition, we demonstrate a facile one-step in situ
      synthesis of FePt NPs with aromatic ligands for better dispersibility in solvents
      of intermediate polarity (polarity index = 1.0-3.5) such as toluene,
      chlorobenzene, and dichloromethane. The creation of stable dispersions of NPs in
      solvents across the polarity spectrum opens up new applications and new
      processing widows for creating NP composites in a variety of host materials. 

PMID- 24460075
TI  - Highly conductive PEDOT:PSS treated with formic acid for ITO-free polymer solar
      cells.
AB  - We proposed a facile film treatment with formic acid to enhance the conductivity
      of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) by 4
      orders of magnitude. The effect of formic acid concentration on conductivity was
      investigated; conductivity increased fast with increasing concentration up to 10
      M and then increased slightly, the highest conductivity being 2050 S cm(-1) using
      26 M concentration. Formic acid treated PEDOT:PSS films also exhibited very high
      transmittances. The mechanism of conductivity enhancement was explored through
      SEM, AFM, and XPS. Formic acid with its high dielectric constant screens the
      charge between PEDOT and PSS bringing about phase separation between them.
      Increased carrier concentration, removal of PSS from the film, morphology, and
      conformation change with elongated and better connected PEDOT chains are the main
      mechanisms of conductivity enhancement. ITO-free polymer solar cells were also
      fabricated using PEDOT:PSS electrodes treated with different concentrations of
      formic acid and showed equal performance to that of ITO electrodes. The
      concentrated acid treatment did not impair the desirable film properties as well
      as stability and performance of the solar cells. 

PMID- 24460078
TI  - Highly chemoselective reduction of amides (primary, secondary, tertiary) to
      alcohols using SmI2/amine/H2O under mild conditions.
AB  - Highly chemoselective direct reduction of primary, secondary, and tertiary amides
      to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C-N bond
      cleavage in the carbinolamine intermediate, shows excellent functional group
      tolerance, and delivers the alcohol products in very high yields. The expected C
      O cleavage products are not formed under the reaction conditions. The observed
      reactivity is opposite to the electrophilicity of polar carbonyl groups resulting
      from the n(X) -> pi*(C?O) (X = O, N) conjugation. Mechanistic studies suggest
      that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the
      tetrahedral intermediate facilitate electron transfer and control the selectivity
      of the C-N/C-O cleavage. Notably, the method provides direct access to acyl-type
      radicals from unactivated amides under mild electron transfer conditions.

PMID- 24460079
TI  - Quantification and bioaccessibility of california pistachio bioactives.
AB  - The content of carotenoids, chlorophylls, phenolics, and tocols in pistachios (
      Pistacia vera L.) has not been methodically quantified. The objective of this
      study was to first optimize extraction protocols for lipophilic nutrients and
      then quantify the content of two phenolic acids, nine flavonoids, four
      carotenoids, two chlorophylls, and three tocols in the skin, nutmeat, and whole
      nut of California pistachios. The dominant bioactives in whole pistachios are
      lutein [42.35 MUg/g fresh weight (FW)], chlorophyll a (142.24 MUg/g FW), gamma
      tocopherol (182.20 MUg/g FW), flavan-3-ols (catechins) (199.18 MUg/g FW),
      luteolin (217.89 MUg/g FW), myricetin (135.18 MUg/g FW), and cyanidin-3-galactose
      (38.34 MUg/g FW) in each nutrient class. Most phenolics are present in the skin,
      while the lipophilic nutrients are dominantly present in the nutmeat. Digestion
      with a gastrointestinal mimic showed <10% of most hydrophilic compounds are
      released from pistachio matrices. In conclusion, 9 lipophilic and 11 hydrophilic
      bioactives in pistachios are systematically quantified. 

PMID- 24460081
TI  - Authors' response to evidence to practice commentary.

PMID- 24460080
TI  - Recovery and time to growth of isolates in blood culture bottles: comparison of
      BD Bactec Plus Aerobic/F and BD Bactec Plus Anaerobic/F bottles.
AB  - BACKGROUND: This study was done to compare the growth of pathogens in paired
      aerobic/anaerobic blood culture bottles versus the use of only aerobic bottles,
      and to analyze the time to growth in both atmospheres. METHODS: We
      retrospectively evaluated the results of all blood cultures collected over a 2-y
      period for the diagnosis of central venous catheter-related bloodstream
      infections or other severe infections in oncology patients. RESULTS: Among the
      487 isolates, 174 (35.7%), all aerobic, grew only in the aerobic bottle; 250
      (51.3%), all aerobic, grew in both bottles; and 63 (12.9%) grew only in the
      anaerobic bottle, of which 24 were anaerobic and 39 were aerobic microorganisms
      (8% of positive blood cultures). Of these 39 aerobic microorganisms, 12 were Gram
      negative, 17 staphylococci (4 were Staphylococcus aureus), 5 streptococci, 2 Gram
      positive bacilli, and 3 mixed growth. Though the mean time to positivity of
      pathogens grown in both atmospheres was significantly lower in the aerobic bottle
      than in the anaerobic bottle, in 71 cases (28.4%) the pathogens developed earlier
      in the anaerobic bottle than in the aerobic bottle - in 36 of these cases at
      least 1 h earlier, which is significant for starting targeted therapy.
      CONCLUSIONS: The use of paired aerobic/anaerobic blood culture bottles allowed
      the diagnosis of a percentage of bacteraemia due to either anaerobic or aerobic
      pathogens that would have been missed, as they grew only in the anaerobic
      atmosphere. Moreover in 8% of bacteraemia we identified a significant decrease in
      the time to detection, resulting in the opportunity to better manage the
      infections without an increase in costs.

PMID- 24460082
TI  - Low but measurable stimulated serum thyroglobulin levels <2 ug/L frequently
      predict incomplete response in differentiated thyroid cancer patients.
AB  - INTRODUCTION: The study was aimed to determine the response and predictive risk
      factors of differentiated thyroid cancer (DTC) with measurable (0.4-2.0 ug/L)
      stimulated serum thyroglobulin (sTg) during the 10-24 months after radioiodine
      remnant ablation (RRA) and their long-term outcomes. METHODS: Out of 839
      retrospectively reviewed patients, 95 eligible DTC patients were included.
      Patients were classified as having incomplete response or no evidence of disease
      (NED). The sTg cut-off values with highest predicted accuracy for incomplete
      response at 10-24 months were calculated with receiver operator characteristics
      curve analysis. RESULTS AND CONCLUSION: At 10-24 months after RRA, incomplete
      response was identified in 54 patients (57%) and 38/54 (70.4%) patients were
      found with structural evidence of disease. The remaining 16 patients (29.6%) had
      biochemical evidence of disease without structural evidence of disease. Forty-one
      patients (43%) were classified as having NED at 10-24 months after RRA and 27
      patients (66%) did not receive further radioactive iodine (RAI) therapy and
      remained disease free at median follow-up of 6.5 years. Fourteen patients
      received second RAI treatment after 6 months and before the 10-24 months
      assessment time point. Of these, 2 had persistent tumor 6 years later. The sTg
      >0.6 ug/L at 6-10 months after RRA had optimal sensitivity (83.3%), specificity
      (56%) and negative predictive value (72%) of detecting incomplete response at 10
      24 months after RRA. A total of 23/43 patients in the American Thyroid
      Association low-risk category had incomplete response after first RRA and 5/23
      (21.7%) had recurrent/persistent disease at long-term follow-up.

PMID- 24460083
TI  - Historical perspectives and future implications.

PMID- 24460084
TI  - Disseminated spinal myxopapillary ependymoma in an adult at initial presentation:
      a case report and review of the literature.
AB  - Disseminated spinal myxopapillary ependymoma (MPE) is extremely rare in adults.
      We report a 63-year-old man with chronic low-back pain found to have multiple
      MPEs in the thoracic, lumbar and sacral spine. Diagnostic and management
      strategies of disseminated MPE are discussed with a review of pertinent
      literature.

PMID- 24460087
TI  - Acta Oncologica Lecture. Gastrointestinal consequences of cancer treatment and
      the wider context: a bad gut feeling.
AB  - BACKGROUND: The percentage of people living with a diagnosis of cancer is rising
      globally. Between 20% and 25% of people treated for cancer experience a
      consequence of cancer which has an adverse impact on the quality of their life.
      Gastrointestinal (GI) symptoms are the most common of all consequences of cancer
      treatment and have the greatest impact on daily activity. PATHOPHYSIOLOGY OF LONG
      TERM BOWEL DAMAGE AFTER PELVIC RADIOTHERAPY: Long-term damage to the bowel after
      radiotherapy is mediated by ischaemic changes and fibrosis. Each fraction of
      radiotherapy causes a series of repetitive injuries to the intestinal tissue
      resulting in an altered healing process, which affects the integrity of the
      repair and changes the architecture of the bowel wall. THE NATURE OF GI SYMPTOMS
      THAT DEVELOP: Patient-reported outcome measures show that diarrhoea, urgency,
      increased bowel frequency, tenesmus and flatulence are the five most prevalent GI
      symptoms with a moderate or severe impact on patients' daily lives after
      treatment with pelvic radiotherapy. Many patients also experience fatigue,
      urinary problems and have sexual concerns. SYSTEMATIC ASSESSMENT AND MANAGEMENT:
      The complex nature of those symptoms warrants systematic assessment and
      management. The use of a tested algorithm can assist in achieving this. The most
      common contributing factors to ongoing bowel problems after pelvic radiotherapy
      are small intestinal bacterial overgrowth, bile acid malabsorption, pancreatic
      insufficiency, rectal bleeding and its impact on bone health. THE WIDER CONTEXT:
      Symptom burden, socio-psychosocial impact, memory and cognitive function,
      fatigue, urinary problems and sexual concerns need to be taken into account when
      thinking about consequences of cancer treatment. CONCLUSION: As our understanding
      of consequences of cancer treatments continues to emerge and encompass a wide
      variety of specialties, a holistic, multifaceted and multidisciplinary approach
      is required to manage those consequences long-term.

PMID- 24460086
TI  - Linear poly(ethylene imine)-based hydrogels for effective binding and release of
      DNA.
AB  - A series of copolymers containing both amine groups of linear poly(ethylene
      imine) (LPEI) and double bonds of poly(2-(3-butenyl)-2-oxazoline) (PButEnOx) was
      prepared. To this end, a poly(2-ethyl-2-oxazoline) (PEtOx) precursor was
      hydrolyzed to the respective LPEI and functionalized in an amidation reaction
      with butenyl groups resulting in the double bond containing poly(2-(3-butenyl-2
      oxazoline)-co-ethylene imine) (P(ButEnOx-co-EI)). Hydrogels were obtained by
      cross-linking with dithiols under UV-irradiation resulting in networks with
      different properties in dependence of the content of double bonds. The developed
      method allows the exact control of the amount of ethylene imine units within the
      copolymer and, thus, within the resulting hydrogels. The gel structures were
      characterized by solid state NMR and infrared spectroscopy. In addition the water
      uptake behavior from the liquid and the gas phase was investigated. It was shown
      by an ethidium bromide assay (EBA) that the copolymers and the respective
      hydrogels were able to bind and release DNA. Furthermore, the influence of the
      ethylene imine content on this interaction was investigated. 

PMID- 24460088
TI  - Trophic magnification and isomer fractionation of perfluoroalkyl substances in
      the food web of Taihu Lake, China.
AB  - Biomagnification of perfluoroalkyl substances (PFASs) are well studied in marine
      food webs, but related information in fresh water ecosystem and knowledge on
      fractionation of their isomers along the food web are limited. The distribution,
      bioaccumulation, magnification, and isomer fractionation of PFASs were
      investigated in a food web of Taihu Lake, China. Perfluorooctanesulfonate (PFOS)
      and perfluorocarboxylates (PFCAs) with longer carbon chain lengths, such as
      perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUnA), were predominant in
      organisms, while perfluorohexanoate (PFHxA) and perfluorooctanoate (?PFOA)
      contributed more in the water phase. The consistent profile signature of PFOA
      isomers in water phase with 3M electrochemical fluorination (ECF) products
      suggests that ECF production of PFOA still exists in China. Linear proportions of
      PFOA, PFOS and perfluorooctane sulfonamide (PFOSA) in the biota were in the range
      of 91.9-100%, 78.6-95.5%, and 72.2-95.5%, respectively, indicating preferential
      bioaccumulation of linear isomers in biota. Trophic magnification factors (TMFs)
      were estimated for PFDA (2.43), perfluorododecanoate (PFDoA) (2.68) and PFOS
      (3.46) when all biota were included, suggesting that PFOS and long-chained PFCAs
      are biomagnified in the fresh water food web. The TMF of PFOS isomers descended
      in the order: n-PFOS (3.86) > 3+5m-PFOS (3.35) > 4m-PFOS (3.32) > 1m-PFOS (2.92)
      > m2-PFOS (2.67) > iso-PFOS (2.59), which is roughly identical to their elution
      order on a FluoroSep-RP Octyl column, suggesting that hydrophobicity may be an
      important contributor for isomer discrimination in biota. 

PMID- 24460089
TI  - Structural parameters determining the strength of the porcine vertebral body
      affected by tumours.
AB  - Spinal metastatic disease could lead to catastrophic consequences for the
      patient. However, the structural parameters that explain the weakening of
      vertebrae affected by tumours are not fully understood. In this study, we
      developed a specimen-specific finite element model to predict the strength of the
      porcine vertebra with simulated tumours and used it to find the structural
      parameters determining the strength. We validated our model with mechanical
      testing and then we analysed the compressive strength of intact vertebrae and
      seven defects with different size and shape. The results showed that the minimum
      bone mineral mass of the cross section and areal defect fraction were the best
      predictors of the normalized strength. We also found that areal parameters
      appeared to be better predictors than the volumetric ones. In conclusion,
      reduction in bone strength for vertebrae weakened by metastatic tumours is mostly
      associated with decrease in the mechanical properties of the cross section. 

PMID- 24460090
TI  - Impact of shape and pore size of mesoporous silica nanoparticles on serum protein
      adsorption and RBCs hemolysis.
AB  - With the rapid development of nanotechnology, mesoporous silica nanoparticles
      (MSNs) with numerous forms and structures have been synthesized and extensively
      applied in biomedicine in the past decades. However, our knowledge about the
      biocompatibility of the developed MSNs has not matched their development.
      Therefore, in this work, we have synthesized sphere-shaped MSNs with different
      pore scales (s-SPs and l-SPs) and rod-shape (RPs-3) MSNs to evaluate the
      influence of the morphology and pore size on their interaction with serum
      proteins and red blood cells (RBCs). The adsorption of human albumin (HSA),
      globulin (HGG), and fibrinogen (HSF) onto different kinds of MSNs has been
      analyzed by pseudo second-order kinetic model, and the conformational changes of
      the adsorbed proteins have been studied by FTIR spectroscopy. We find that the
      conformation of absorbed HSA and HSF, while not HGG, will be affected by the pore
      size and morphology of the MSNs. The conformational changes of the adsorbed
      proteins will further affect their saturated adsorption capacity. However, the
      initial adsorption rate is only determined by the property of MSNs and proteins.
      Additional hemolysis assay shows that the pore size and morphology of the MSNs
      will also affect their hemolytic activity in RBCs which will be extremely
      depressed by the formation of protein corona. These systematic studies will
      provide an overall understanding in the blood compatibility of MSNs as well as
      useful guidelines for fabrication of blood-compatible nanomaterials. 

PMID- 24460091
TI  - Emulsifying properties and oil/water (O/W) interface adsorption behavior of
      heated soy proteins: effects of heating concentration, homogenizer rotating
      speed, and salt addition level.
AB  - The adsorption of heat-denatured soy proteins at the oil/water (O/W) interface
      during emulsification was studied. Protein samples were prepared by heating
      protein solutions at concentrations of 1-5% (w/v) and were then diluted to 0.3%
      (w/v). The results showed that soy proteins that had been heated at higher
      concentrations generated smaller droplet size of emulsion. Increase in
      homogenizer rotating speed resulted in higher protein adsorption percentages and
      lower surface loads at the O/W interface. Surface loads for both unheated and
      heated soy proteins were linearly correlated with the unadsorbed proteins'
      equilibrium concentration at various rotating speeds. With the rise in NaCl
      addition level, protein adsorption percentage and surface loads of emulsions
      increased, whereas lower droplet sizes were obtained at the ionic strength of 0.1
      M. The aggregates and non-aggregates displayed different adsorption behaviors
      when rotating speed or NaCl concentration was varied. 

PMID- 24460092
TI  - Phenothiazine-modified electrodes: a useful platform for protein adsorption
      study.
AB  - Using glucose oxidase (GOx) as a target protein, we studied the adsorption of
      protein on the phenothiazine-modified electrodes and assessed the potential of
      using the electrodes in biochemical applications. Experiment results showed that
      thionine chloride (TC) and its structural analogues, such as toluidine blue and
      methylene blue, fluoresced under photochemical excitation after being immobilized
      on indium-doped tin oxide (ITO) electrodes fabricated using either diazotization
      reduction or oxidative polymerization. The surface-bound phenothiazines exhibited
      substantial binding affinities to the protein. At a pH > 5, the adsorbate showed
      no sign of desorption even the electrodes were electrically biased with voltages
      between +/-0.3 V vs SCE. Thus, emission decay occurred while GOx was injected
      over the electrodes, which was consistent with the observations made using
      conductive-mode atomic force microscopy (CM-AFM). Under a quiescent condition,
      the protein interacted with the immobilized TC via a pseudo-first-order kinetic
      mechanism. The reaction reached a maximum rate at a pH > 5, at which the rate
      constant was approximately 7 * 10(-8) L/(U s). Under this condition, the
      adsorption rate increased as the level of the protein increased, regardless of
      pH, revealing application potential for GOx quantitation. The adsorption rate,
      however, decreased with a decrease in pH if the pH < 5. We concluded that static
      interactions played a crucial role. By monitoring Fe(CN)6(3-/4-) taking place at
      the TC-modified electrodes in pH 7 solutions, we observed that the adsorption of
      GOx imposed impedance on Fe(CN)6(3-/4-). The resulting charge-transfer resistance
      (RCT) increased as the amount of the protein increased, leading to a conclusion
      that the protein could reach the maximum surface coverage when its concentrations
      were greater than 100 U/mL. The protein molecules were likely repel each other as
      approaching the TC sites. Despite this, they maintained the native bioactivity
      after being adsorbed, enabling the TC-modified electrodes to function as glucose
      sensors. Glucose concentrations between 1 and 60 mM could be detected. Long-term
      analysis, in addition, showed that the electrode responses to the analyte were
      consistent and reproducible. Phenothiazine-modified electrodes are evident as a
      useful tool for understanding the adsorption of protein on solid surfaces and
      quantifying proteins. 

PMID- 24460093
TI  - Photoinduced interfacial electron transfer within a mesoporous transparent
      conducting oxide film.
AB  - Interfacial electron transfer to and from conductive Sn-doped In2O3 (ITO)
      nanoparticles (NPs) in mesoporous thin films has been investigated by transient
      absorption measurements using surface-bound [Ru(II)(bpy)2(dcb)](2+) (bpy is 2,2'
      bipyridyl and dcb is 4,4'-(COOH)2-2,2'-bipyridyl). Metal-to-ligand charge
      transfer excitation in 0.1 M LiClO4 MeCN results in efficient electron injection
      into the ITO NPs on the picosecond time scale followed by back electron transfer
      on the nanosecond time scale. Rates of back electron transfer are dependent on
      thermal annealing conditions with the rate constant increasing from 1.8 * 10(8)
      s(-1) for oxidizing annealing conditions to 8.0 * 10(8) s(-1) for reducing
      conditions, presumably due to an enhanced electron concentration in the latter. 

PMID- 24460095
TI  - Visualizing site-specific redox potentials on the surface of plasmonic
      nanoparticle aggregates with superlocalization SERS microscopy.
AB  - In this Letter, we demonstrate site-specific redox potentials for Nile Blue
      adsorbed to Ag nanoparticle electrodes using surface-enhanced Raman scattering
      (SERS) superlocalization microscopy. Nile Blue is electrochemically modulated
      between its oxidized and reduced form, which can be optically read out through a
      corresponding gain or loss in SERS intensity. SERS emission centroids are
      calculated by fitting the diffraction-limited SERS emission to a two-dimensional
      Gaussian to determine the approximate location of the emitter with 5-10 nm
      precision. With molecular coverage above the single molecule level, the SERS
      centroid trajectories shift reversibly with applied potential over multiple
      reduction and oxidation cycles. A mechanism is proposed to explain the centroid
      trajectories based on site-specific redox potentials on the nanoparticle
      electrode surface, where the first molecule reduced is the last to be oxidized,
      consistent with reversible electrochemical behavior of redox probes adsorbed to
      electrode surfaces. 

PMID- 24460096
TI  - The joint influence of collaboration and part-set cueing.
AB  - The present study was designed to examine the effects of retrieval cues on memory
      performance for both individuals and collaborating pairs. Participants worked
      either alone or together in the presence or absence of part-set cues to recall
      list items in Experiments 1 and 2 and to reconstruct the order of a list items in
      Experiment 3. The detrimental effects of collaborative inhibition were observed
      across all three experiments. In contrast, part-set cueing inhibition was found
      following free recall, whereas part-set cueing facilitation was observed on
      reconstruction tasks. Taken together, the results of the present experiments
      suggest that the effects of collaborative inhibition and part-set cueing may
      operate independently of one another.

PMID- 24460097
TI  - Radiation processing of formamide and formamide:water ices on silicate grain
      analogue.
AB  - Lyman-alpha (121.6 nm) photon and 1 keV electron-beam irradiation of pure HCONH2
      (FA) ice and H2O:HCONH2 ice mixtures on high-surface-area SiO2 nanoparticles have
      been investigated with FT-IR spectroscopy and temperature programmed desorption
      (TPD). Lyman-alpha photolysis of pure amorphous FA ice grown at 70 K and
      crystalline FA ice produced by annealing to 165 K gives spectral signatures
      between 2120 and 2195 cm(-1) that we assign primarily to OCN(-) and CO. The OCN(
      ) and CO yields are ~25% less abundant for crystalline FA ice. Photon and
      electron processing also produces H2 that is released from the ice between ~90
      and 140 K. A decrease in the H2 TPD peak is seen for irradiated crystalline
      HCONH2 ice. Lyman-alpha photolysis of H2O:HCONH2 mixed ices increases OCN(-) and
      CO production, suggesting a catalytic role of H2O. Also, for pure FA, 1 keV
      electron irradiation slightly increases the yield of OCN(-), while CO
      decarboxylation is selectively prevented. CO is also not produced in H2O:HCONH2
      ices upon electron irradiation. Dissociative ionization, direct dissociative
      excitation, and dissociative electron attachment (DEA) channels are accessible in
      the Lyman-alpha (121.6 nm) photon and 1 keV electron-beam energy range. DEA
      energetically favors OCN(-) and H(-) formation, with the latter leading to H2
      formation. The FA fragment product identities, yields, and branching ratios are
      considerably different relative to the gas phase and depend upon the radiation
      type, ice structure, and the presence of SiO2 nanoparticles. The latter may
      increase ion-electron recombination and radical recombination rates. The main
      products observed suggest very different condensed-phase dissociation channels
      from those reported for gas-phase dissociation. Formation of ions/products from
      FA is not negligible upon Lyman-alpha photolysis or electron irradiation, both of
      which could process ices in interstellar regions as well as in Titan's
      atmosphere. 

PMID- 24460099
TI  - Safety of high-dose micafungin for patients with hematological diseases.
AB  - This study was conducted as a retrospective, observational, exploratory cohort
      study with the aim of elucidating the safety profile of micafungin at doses
      exceeding 150 mg daily. We identified adult patients with hematological diseases
      who had received micafungin therapy for >= 7 consecutive days. Twenty-six
      patients administered micafungin at 300 mg daily (high-dose group) were compared
      with 58 patients administered micafungin at 150 mg daily (standard-dose group).
      The most frequent adverse events (AEs) were hepatotoxicity, hypertension and
      diarrhea. AEs were recorded in 42 (72%) and 19 (73%) patients in the standard
      dose and high-dose groups, respectively (p = 1.00). Hepatobiliary AEs were noted
      in 28 (48%) and 15 (58%) patients, respectively (p = 0.48). Serious AEs and
      resultant treatment discontinuation were infrequent. Our results suggest that
      micafungin was safe and well tolerated at 300 mg daily.

PMID- 24460100
TI  - Pilot study of variants of the IL-23R and STAT3 genes reveals no association with
      Hashimoto's thyroiditis in the Croatian population.
AB  - Interleukin-23 receptor (IL-23R) and signal transducer and activator of
      transcription 3 (STAT3) polymorphisms are common risk factors for a number of T
      helper (Th) 17-mediated autoimmune diseases. However, the importance of genetic
      variations in Th17 pathways to thyroid autoimmunity, and particularly Hashimoto's
      thyroiditis (HT), is not fully understood. In this study, we genotyped three
      single nucleotide polymorphisms (SNPs) within the IL-23R (rs11209026/p.Arg381Gln,
      rs7530511) and STAT3 (rs744166) genes in 217 Croatian patients with HT and 161
      healthy controls using fluorescence resonance energy transfer technology and
      melting curve analysis of polymerase chain reaction products. None of the tested
      SNPs or IL-23R haplotypes was associated with HT susceptibility or disease
      severity. These results suggest that the studied IL-23R/STAT3 polymorphisms
      affecting Th17 signaling efficiency are not major determinants of HT risk in the
      Croatian population. Further work is necessary to determine if these loci
      contribute modestly or conditionally to the risk of HT.

PMID- 24460101
TI  - Toroidal-spiral particles for codelivery of anti-VEGFR-2 antibody and irinotecan:
      a potential implant to hinder recurrence of glioblastoma multiforme.
AB  - Heterogeneous toroidal-spiral particles (TSPs) were generated by polymer droplet
      sedimentation, interaction, and cross-linking. TSPs provide a platform for
      encapsulation and release of multiple compounds of different sizes and
      physicochemical properties. As a model system, we demonstrate the encapsulation
      and independently controlled release of an anti-VEGFR-2 antibody and irinotecan
      for the treatment of glioblastoma multiforme. The anti-VEGFR-2 antibody was
      released from the TS channels and its binding to HUVECs was confirmed by confocal
      microscopy and flow cytometry, suggesting active antibody encapsulation and
      release. Irinotecan, a small molecule drug, was released from the dense polymer
      matrix of poly(ethylene glycol) diacrylate (MW ~ 700 g/mol; PEGDA 700). Released
      irinotecan inhibited the proliferation of U251 malignant glioma cells. Since the
      therapeutic compounds are released through different pathways, specifically
      diffusion through the polymer matrix versus TS channels, the release rate can be
      controlled independently through the design of the structure and material of
      particle components.

PMID- 24460102
TI  - Computing the electrophoretic mobility of large spherical colloids by combining
      explicit ion simulations with the standard electrokinetic model.
AB  - The electrophoretic mobility of large spherical colloids in different salt
      solutions of varying valency and concentration is studied via a combination
      approach of numerically solving the standard electrokinetic model with a zeta
      potential that has been obtained from explicit ion simulations of the restricted
      primitive model, thus going beyond the standard mean-field treatment. We compare
      our theoretical mobility curves to two distinct sets of experimental results and
      obtain good agreement for monovalent and divalent salt solutions. For the case of
      the trivalent La(3+) salt, the experimentally obtained mobility reversal at high
      ionic strengths can be obtained only by adding an additional attractive
      interaction of 4k(B)T to the potential between the colloid and La(3+), hinting at
      the presence of a nonelectrostatic binding term for this ion. It is also shown
      that, contrary to intuition, charge inversion does not necessarily result in
      mobility reversal.

PMID- 24460103
TI  - Mixing in colliding, ultrasonically levitated drops.
AB  - Lab-in-a-drop, using ultrasonic levitation, has been actively investigated for
      the last two decades. Benefits include lack of contact between solutions and an
      apparatus and a lack of sample cross-contamination. Understanding and controlling
      mixing in the levitated drop is necessary for using an acoustically levitated
      drop as a microreactor, particularly for studying kinetics. A pulsed
      electrostatic delivery system enables addition and mixing of a desired-volume
      droplet with the levitated drop. Measurement of mixing kinetics is obtained by
      high-speed video monitoring of a titration reaction. Drop heterogeneity is
      visualized as 370 nl of 0.25 M KOH (pH: 13.4) was added to 3.7 MUL of 0.058 M HCl
      (pH: 1.24). Spontaneous mixing time is about 2 s. Following droplet impact, the
      mixed drop orbits the levitator axis at about 5 Hz during homogenization. The
      video's green channel (maximum response near 540 nm) shows the color change due
      to phenolphthalein absorption. While mixing is at least an order of magnitude
      faster in the levitated drop compared with three-dimensional diffusion,
      modulation of the acoustic waveform near the surface acoustic wave resonance
      frequency of the levitated drop does not substantially reduce mixing time. 

PMID- 24460105
TI  - Protein binding associated with exposure to fluorotelomer alcohols (FTOHs) and
      polyfluoroalkyl phosphate esters (PAPs) in rats.
AB  - The biotransformation of fluorotelomer-based compounds such as fluorotelomer
      alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are sources of
      exposure to perfluorinated carboxylates (PFCAs), leading in part to the
      observation of significant concentrations of PFCAs in human blood. The
      biotransformation of FTOHs and PAPs yield intermediate metabolites that have been
      observed to covalently modify proteins. In the current investigation, the extent
      of covalent protein binding in Sprague-Dawley rats upon exposure to 8:2 FTOH and
      the 6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) was quantified. The animals
      were administered a single dose of 8:2 FTOH or 6:2 diPAP at 100 mg/kg by oral
      gavage to monitor biotransformation and extent of protein binding within the
      liver, kidney, and plasma. In the 8:2 FTOH-dosed animals, perfluorooctanoate
      (PFOA) was produced as the primary PFCA, at 623.13 +/- 59.3, 459.5 +/- 171.8, and
      397.3 +/- 133.0 ng/g in the plasma, liver, and kidney, respectively. For the
      animals exposed to 6:2 diPAPs, perfluorohexanoate (PFHxA) was the primary PFCA
      produced, with maximum concentrations of 57.4 +/- 6.5, 9.0 +/- 1.2, and 25.3 +/-
      1.2 ng/g in the plasma, liver, and kidney, respectively. Protein binding was
      observed in the plasma, liver, and kidney after 8:2 FTOH and 6:2 diPAP exposure,
      with the most significant binding occurring in the liver (>100 nmol/g protein).
      This is the first study to link the exposure and in vivo biotransformation of
      fluorotelomer-based compounds to covalent protein binding. 

PMID- 24460107
TI  - Incomplete periacetabular acetabuloplasty.
AB  - BACKGROUND: Residual acetabular dysplasia is one of the most common complications
      after treatment for developmental dysplasia of the hip. The acetabular growth
      response after reduction of a dislocated hip varies. The options are to wait and
      add a redirectional osteotomy as a secondary procedure at an older age, or to
      perform a primary acetabuloplasty at the time of the open reduction to stimulate
      acetabular development. We present the early results of such a procedure-open
      reduction and an incomplete periacetabular acetabuloplasty-as a one-stop
      procedure for developmental dysplasia of the hip. PATIENTS AND METHODS: We
      retrospectively reviewed the results obtained with 55 hips (in 48 patients, 43 of
      them girls) treated between September 2004 and February 2011. This cohort
      included late presentations and failures of nonoperative treatment and excluded
      unsuccessful previous surgical treatment (including closed reductions),
      neuromuscular disease, and other teratological conditions. Patients were treated
      once the ossific nucleus was present or when they reached one year of age. 31
      cases were late presentations while 17 represented failures of nonoperative
      treatment. The mean age of the patients at surgery was 1.3 (0.6-2.6) years. The
      mean follow-up period was 4 (2-8) years. According to the IHDI classification, 1
      was grade I, 9 were grade II, 13 were grade III, and 32 were grade IV. Results
      The mean acetabular index fell from 38 (23-49) preoperatively to 21 (10-27) at
      the last follow-up. There were no infections, nerve palsies, or graft extrusions.
      None of the cases required secondary surgery for residual acetabular dysplasia. 8
      patients developed avascular necrosis (AVN) of grade II or more. The incidence of
      AVN was significantly associated with previous, failed nonoperative treatment. 1
      patient developed coxa magna requiring shelf arthroplasty 4 years after the index
      procedure and 1 patient with lateral growth arrest required medial screw
      epiphysiodesis. INTERPRETATION: This incomplete periacetabular acetabuloplasty is
      a reliable adjunct to open reductions, and it is followed by a rapid acetabular
      growth response that avoids secondary pelvic procedures. It is a one-stop surgery
      with predictable outcome that can be performed in 0.5- to 2.5-year-old children.

PMID- 24460108
TI  - Posterior approach and uncemented stems increases the risk of reoperation after
      hemiarthroplasties in elderly hip fracture patients.
AB  - BACKGROUND: Hemiarthroplasties are performed in great numbers worldwide but are
      seldom registered on a national basis. Our aim was to identify risk factors for
      reoperation after fracture-related hemiarthroplasty in Norway and Sweden.
      MATERIAL AND METHODS: A common dataset was created based on the Norwegian Hip
      Fracture Register and the Swedish Hip Arthroplasty Register. 33,205 hip fractures
      in individuals > 60 years of age treated with modular hemiarthroplasties were
      reported for the period 2005-2010. Cox regression analyses based on reoperations
      were performed (covariates: age group, sex, type of stem and implant head,
      surgical approach, and hospital volume). RESULTS: 1,164 patients (3.5%) were
      reoperated during a mean follow-up of 2.7 (SD 1.7) years. In patients over 85
      years, an increased risk of reoperation was found for uncemented stems (HR = 2.2,
      95% CI: 1.7-2.8), bipolar heads (HR = 1.4, CI: 1.2-1.8), posterior approach (HR =
      1.4, CI: 1.2-1.8) and male sex (HR = 1.3, CI: 1.0-1.6). For patients aged 75-85
      years, uncemented stems (HR = 1.6, 95% CI: 1.2-2.0) and men (HR = 1.3, CI: 1.1
      1.6) carried an increased risk. Increased risk of reoperation due to infection
      was found for patients aged < 75 years (HR = 1.5, CI: 1.1-2.0) and for uncemented
      stems. For open surgery due to dislocation, the strongest risk factor was a
      posterior approach (HR = 2.2, CI: 1.8-2.6). Uncemented stems in particular (HR =
      3.6, CI: 2.4-5.3) and male sex increased the risk of periprosthetic fracture
      surgery. INTERPRETATION: Cemented stems and a direct lateral transgluteal
      approach reduced the risk of reoperation after hip fractures treated with
      hemiarthroplasty in patients over 75 years. Men and younger patients had a higher
      risk of reoperation. For the age group 60-74 years, there were no such
      differences in risk in this material.

PMID- 24460109
TI  - Atypical fracture of the femur in a patient using denosumab--a case report.

PMID- 24460110
TI  - Postoperative urinary retention (POUR) in fast-track total hip and knee
      arthroplasty.

PMID- 24460111
TI  - Cystic ganglioneurocytoma of the lateral ventricles.
AB  - A 52-year-old woman displayed a brain-MRI depicting a left lateral ventricle
      mass, associated with cystic component, extending controlaterally. Histological
      examination revealed neuronal differentiation with neurocytes and small
      ganglionic cells and the tumour was graded as a ganglioneurocytoma. We report the
      first case of a cystic ganglioneurocytoma with an intraventricular location.

PMID- 24460112
TI  - On the flexibility of metal-organic frameworks.
AB  - Occasional, large amplitude flexibility in metal-organic frameworks (MOFs) is one
      of the most intriguing recent discoveries in chemistry and material science. Yet,
      there is at present no theoretical framework that permits the identification of
      flexible structures in the rapidly expanding universe of MOFs. Here, we propose a
      simple method to predict whether a MOF is flexible, based on treating it as a
      system of rigid elements, connected by hinges. This proposition is correct in
      application to MOFs based on rigid carboxylate linkers. We validate the method by
      correctly classifying known experimental MOFs into rigid and flexible groups.
      Applied to hypothetical MOFs, the method reveals an abundance of flexibility
      phenomena, and this seems to be at odds with the proportion of flexible
      structures among experimentally known MOFs. We speculate that the flexibility of
      a MOF may constitute an intrinsic impediment on its experimental realization.
      This highlights the importance of systematic prediction of large amplitude
      flexibility regimes in MOFs. 

PMID- 24460114
TI  - Cooperation/Collaboration.

PMID- 24460115
TI  - There is no association between the serotonin receptor gene and bipolar I
      disorder in the Korean population.
AB  - OBJECTIVE: Despite the close relationship between the functional polymorphism C(
      1019)G (rs6295) of the serotonergic 1A receptor (5-HT1A) and mood, few studies
      have investigated the relationship between rs6295 and bipolar disorder. AIMS: In
      this study, we aimed to investigate whether rs6295 is associated with clinical
      prognosis and treatment response in patients with bipolar I disorder acute manic
      episodes. METHODS: One hundred twenty-eight patients with bipolar I disorder and
      one hundred sixty-eight healthy controls were recruited. Associations between
      patients with bipolar I disorder and healthy controls were compared. In addition,
      age at onset, number of admissions, and treatment response, including response
      rate, mean changes in manic symptoms, number of anti-manic agents and the total
      dosage of mood stabilizers for acute manic symptoms were compared between the
      rs6295 GG and CG+ CC groups in patients with bipolar I disorder. We conducted a
      separate subgroup analysis according to gender. RESULTS: There were no
      differences in frequency between patients and controls. In patients with bipolar
      disorder, clinical prognosis and treatment response were no different between GG
      and CG+ CC groups. However, in a subgroup analysis according to gender, male, but
      not female, patients in the GG group had a longer duration of illness and a
      greater number of both previous episodes and psychiatric ward admissions than did
      the GC+ CC group. CONCLUSIONS: Further studies should investigate the
      relationship between 5-HT1A polymorphisms and bipolar disorder in terms of mood
      episode and gender.

PMID- 24460116
TI  - Psychometric properties and factor structure of the Swedish version of the
      Perceived Stress Scale.
AB  - BACKGROUND: The Perceived Stress Scale (PSS) measures general stress and the
      Swedish version, although used in several studies, has not been extensively
      evaluated for psychometric properties. AIMS: This study aimed to investigate
      psychometric properties and the factor solution of the Swedish 14-item version
      when used with two samples, namely a mixed Internet sample of women and men (n =
      171) and another of women with stress-related disorders (n = 84). Classical test
      theory, including confirmatory factor analysis, was employed. RESULTS: The factor
      structure supported a two-factor model for the PSS and confirmed other language
      versions of the PSS, although one items showed a low item-total correlation. The
      PSS showed to be feasible with the investigated samples and the results indicated
      no ceiling or floor effects and good internal consistency of the PSS. Several
      aspects of construct validity were shown. An association of - 0.66 between the
      PSS and a measure of coping indicated good concurrent validity. Criterion
      validity was demonstrated through a statistically significant difference (P <
      0.001) between the women with stress-related disorders and the Internet sample.
      Predictive validity of the PSS could be demonstrated in a short-term perspective.
      Based on the sample with stress-related disorders, sensitivity to change was
      shown through a statistically significant stress reduction (P < 0.001) from
      entering work rehabilitation to discharge. CONCLUSIONS: The Swedish version of
      the PSS showed satisfactory psychometric properties and may be recommended for
      use with people with and without known stress-related disorders.

PMID- 24460118
TI  - Photovoltachromic device with a micropatterned bifunctional counter electrode.
AB  - A photovoltachromic window can potentially act as a smart glass skin which
      generates electric energy as a common dye-sensitized solar cell and, at the same
      time, control the incoming energy flux by reacting to even small modifications in
      the solar radiation intensity. We report here the successful implementation of a
      novel architecture of a photovoltachromic cell based on an engineered
      bifunctional counter electrode consisting of two physically separated platinum
      and tungsten oxide regions, which are arranged to form complementary comb-like
      patterns. Solar light is partially harvested by a dye-sensitized photoelectrode
      made on the front glass of the cell which fully overlaps a bifunctional counter
      electrode made on the back glass. When the cell is illuminated, the photovoltage
      drives electrons into the electrochromic stripes through the photoelectrochromic
      circuit and promotes the Li(+) diffusion towards the WO3 film, which thus turns
      into its colored state: a photocoloration efficiency of 17 cm(2) min(-1) W(-1) at
      a wavelength of 650 nm under 1.0 sun was reported along with fast response
      (coloration time <2 s and bleaching time <5 s). A fairly efficient photovoltaic
      functionality was also retained due to the copresence of the independently
      switchable micropatterned platinum electrode. 

PMID- 24460120
TI  - Cryptogenic stroke and diabetes: a probable link between silent atrial
      fibrillation episodes and cerebrovascular disease.
AB  - Diabetes mellitus is a risk factor for cardiovascular and cerebrovascular events
      independently of other factors such as age, sex, BMI and blood pressure. Diabetes
      plays an important role in the pathogenesis of atrial fibrillation because it
      causes alterations to the autonomic nervous system. It may also be associated
      with an increased prevalence of asymptomatic episodes of atrial fibrillation,
      which cause cerebrovascular disease more often than chronic atrial fibrillation.
      The presence of silent cerebral ischemia doubles the risk of stroke in the
      general population independently of other cardiovascular risk factors; therefore,
      early detection of these episodes is important to determine preventive measures
      against the first cerebrovascular disease. 

PMID- 24460121
TI  - Broadband surface plasmon polariton directional coupling via asymmetric optical
      slot nanoantenna pair.
AB  - Surface plasmon polariton (SPP) coupling is a basic subject for plasmonic study
      and applications. Optical nanoantennas enable downscaling of the SPP coupling to
      subwavelength scales. In this study, asymmetric optical slot nanoantenna pairs
      composed of two optical slot nanoantennas with different lengths are proposed for
      SPP directional coupling. Broadband unidirectional launching of SPPs is achieved,
      and the extinction ratio obtained experimentally reaches up to 44. The bandwidth
      is larger than 157 nm. Furthermore, SPP direction-selective radiation is
      demonstrated using the asymmetric optical slot nanoantenna pairs. A novel
      plasmonic display device showing the propagation direction of SPPs is achieved by
      employing asymmetric optical slot nanoantenna pairs without any electric device.
      Asymmetric optical slot nanoantenna pairs have large potential in the directional
      control of SPP launching and radiation and can be very useful in compact optical
      circuits and other photonic integrations. 

PMID- 24460123
TI  - Molecular dynamics simulations of the adenosine A2a receptor in POPC and POPE
      lipid bilayers: effects of membrane on protein behavior.
AB  - Analysis of 300 ns (ns) molecular dynamics (MD) simulations of an adenosine A2a
      receptor (A2a AR) model, conducted in triplicate, in 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC) and 1-palmitoyl-2-oleoylphosphatidylethanolamine
      (POPE) bilayers reveals significantly different protein dynamical behavior.
      Principal component analysis (PCA) shows that the dissimilarities stem from
      interhelical rather than intrahelical motions. The difference in the hydrophobic
      thicknesses of these simulated lipid bilayers is potentially a significant reason
      for the observed difference in results. The distinct lipid headgroups might also
      lead to different molecular interactions and hence different protein loop
      motions. Overall, the A2a AR shows higher mobility and flexibility in POPC as
      compared to POPE. 

PMID- 24460124
TI  - Inkjet printing of layer-by-layer assembled poly(lactide) stereocomplex with
      encapsulated proteins.
AB  - Inkjet printing, a technique that precisely deposits liquid droplets in picoliter
      volume ranges on a substrate, has received increased attention for its novelty
      and ability to produce functional materials. This technology is considered one of
      the most promising methods for the controlled deposition of different polymers.
      In our previous study, a poly(lactide) (PLA) stereocomplex was fabricated using
      inkjet printing on a substrate. The stereocomplex was formed by the layer-by
      layer (LbL) stepwise deposition of poly(l-lactide) (PLLA) and poly(d-lactide)
      (PDLA). Multiple inkjet passes could conclusively improve the PLAs crystal
      structure with solvent evaporation (solidification) and dissolution of PLA. We
      suggested that this technique may also be applicable for fabricating polymer
      composites with drugs, such as peptides, proteins, and nanoparticles, which is
      incompatible with the PLA. Here, we report the utilization of this technique to
      create a PLA stereocomplex with drugs as a drug carrier/reservoir. The three
      components of PLLA, PDLA, and model drugs (an 8-mer peptide, ovalbumin, and
      protein-encapsulating nanoparticles) were alternately overprinted onto the
      substrate without an intermediate rinsing step. Inkjet printing was used
      successfully to form PLA stereocomplex composites with drugs by the LbL
      deposition of polymers and functioned as drug carriers/reservoirs. The sustained
      release of the drugs was observed from the PLLA/PDLA/drug composites. By varying
      the crystalline structure of PLAs-drug composites, the release kinetics of drugs
      could be altered and controlled efficiently. Moreover, a high drug loading
      content (wt %) of PLA stereocomplex composites was achieved up to 100 wt %
      loading, and the composites with 50 wt % of drug loading content were available
      for sustained-release formulation. This fabrication technique would provide a
      platform for creating protein/vaccine/gene delivery carriers with the desired
      release profiles by controlling the microphase-separated structure and drug
      distribution within the composites. 

PMID- 24460125
TI  - Submissions remain healthy, so there is something of a backlog to appear in
      print.

PMID- 24460126
TI  - Experimental characterization of the hydride 1H shielding tensors for HIrX2(PR3)2
      and HRhCl2(PR3)2: extremely shielded hydride protons with unusually large
      magnetic shielding anisotropies.
AB  - The hydride proton magnetic shielding tensors for a series of iridium(III) and
      rhodium(III) complexes are determined. Although it has long been known that
      hydridic protons for transition-metal hydrides are often extremely shielded, this
      is the first experimental determination of the shielding tensors for such
      complexes. Isolating the (1)H NMR signal for a hydride proton requires careful
      experimental strategies because the spectra are generally dominated by ligand
      (1)H signals. We show that this can be accomplished for complexes containing as
      many as 66 ligand protons by substituting the latter with deuterium and by using
      hyperbolic secant pulses to selectively irradiate the hydride proton signal. We
      also demonstrate that the quality of the results is improved by performing
      experiments at the highest practical magnetic field (21.14 T for the work
      presented here). The hydride protons for iridium hydride complexes HIrX2(PR3)2 (X
      = Cl, Br, or I; R = isopropyl, cyclohexyl) are highly shielded with isotropic
      chemical shifts of approximately -50 ppm and are also highly anisotropic, with
      spans (=delta11 - delta33) ranging from 85.1 to 110.7 ppm. The hydridic protons
      for related rhodium complexes HRhCl2(PR3)2 also have unusual magnetic shielding
      properties with chemical shifts and spans of approximately -32 and 85 ppm,
      respectively. Relativistic density functional theory computations were performed
      to determine the orientation of the principal components of the hydride proton
      shielding tensors and to provide insights into the origin of these highly
      anisotropic shielding tensors. The results of our computations agree well with
      experiment, and our conclusions concerning the importance of relativistic effects
      support those recently reported by Kaupp and co-workers. 

PMID- 24460127
TI  - Determining possible thrombus sites in an extracorporeal device, using
      computational fluid dynamics-derived relative residence time.
AB  - The prediction of conditions that may result in thrombus formation is a useful
      application of computational fluid dynamics. A number of techniques exist, based
      on the consideration of wall shear stress and regions of low blood flow; however,
      no clear guideline exists for the best practice of their use. In this paper, the
      sensitivity of each parameter and the specific mechanical forces are explained,
      before the optimal indicator of thrombosis risk is outlined. An extracorporeal
      access device cavity provides a suitable geometry to test the methodology. The
      recommended method for thrombus prediction considers areas with a calculated
      residence time (RT) and shear strain rate (SSR) thresholds, here set to RT>1 and
      SSR < 10 s(- 1). Evidence of thrombosis was found for physiological waveforms
      with an absence of reverse flow, which is expected to 'wash out' the cavity. The
      predicted thrombosis sites compare well with evidence collected from explanted
      devices. 

PMID- 24460129
TI  - Highly selective enrichment of N-linked glycan by carbon-functionalized ordered
      graphene/mesoporous silica composites.
AB  - Abnormal protein glycosylation has been demonstrated to be associated with many
      diseases; therefore, it is very important to conduct a comprehensive structure
      analysis of glycan for prognosis and diagnosis of diseases, such as cancer. In
      this work, for the first time, carbon-functionalized ordered graphene/mesoporous
      silica composites (denoted as C-graphene@mSiO2) with large surface area and
      uniform pore size were designed and synthesized. By taking advantage of the
      special interaction between the carbon and glycans as well as size-exclusion
      ability, 25 N-linked glycans released from ovalbumin were observed clearly with
      strong MS signals and increased signal-to-noise (S/N) ratio. In addition, after
      enrichment with the C-graphene@mSiO2 composites, 48 N-linked glycans (S/N > 10)
      with sufficient peak intensities were obtained from only 400 nL of healthy
      pristine human serum. The facile and low-cost synthesis method as well as high
      selective enrichment ability of the novel C-graphene@mSiO2 composite makes it a
      promising tool for glycosylation research. 

PMID- 24460130
TI  - Glyco-nanoparticles with sheddable saccharide shells: a unique and potent
      platform for hepatoma-targeting delivery of anticancer drugs.
AB  - Reduction-sensitive shell-sheddable glyco-nanoparticles were designed and
      developed based on poly(epsilon-caprolactone)-graft-SS-lactobionic acid (PCL-g-SS
      LBA) copolymer for efficient hepatoma-targeting delivery of doxorubicin (DOX).
      PCL-g-SS-LBA was prepared by ring-opening copolymerization of epsilon
      caprolactone and pyridyl disulfide carbonate followed by postpolymerization
      modification with thiolated lactobionic acid (LBA-SH) via thiol-disulfide
      exchange reaction. The dynamic light scattering (DLS) and transmission electron
      microscopy (TEM) showed that PCL-g-SS-LBA was self-assembled into monodisperse
      nanoparticles (SS-GNs) with a mean diameter of about 80 nm. SS-GNs while
      remaining stable under physiological conditions (37  degrees C, pH 7.4) were
      prone to rapid shell-shedding and aggregation in the presence of 10 mM
      dithiothreitol (DTT). DOX was loaded into SS-GNs with a decent loading content of
      12.0 wt %. Notably, in vitro release studies revealed that about 80.3% DOX was
      released from DOX-loaded SS-GNs in 24 h under a reductive condition while low
      drug release (<21%) was observed for DOX-loaded PCL-g-LBA nanoparticles
      (reduction-insensitive control) under otherwise the same condition and for DOX
      loaded SS-GNs under a nonreductive condition. The flow cytometry and confocal
      microscopy observations indicated that SS-GNs were efficiently taken up by
      asialoglycoprotein receptor (ASGP-R)-overexpressing HepG2 cells likely via a
      receptor-mediated endocytosis mechanism and DOX was released into the nuclei of
      cells following 4 h incubation. MTT assays showed that DOX-loaded SS-GNs
      exhibited a high antitumor activity toward HepG2 cells, which was comparable to
      free DOX and about 18-fold higher than their reduction-insensitive counterparts,
      while blank SS-GNs were nontoxic up to a tested concentration of 1.0 mg/mL. These
      shell-sheddable glyco-nanoparticles are promising for hepatoma-targeting
      chemotherapy. 

PMID- 24460131
TI  - Absorption of americium compounds in the respiratory tract.
AB  - PURPOSE: To improve the dosimetry of incorporated americium (Am) and to
      contribute to radiation protection by characterizing the absorption kinetics of
      inhaled Am compounds. MATERIAL AND METHODS: In vitro dissolution tests, animal
      experiments and human contamination cases published in the literature were
      reviewed. The data were analyzed with biokinetic models consistent with the
      current publications of the International Commission on Radiological Protection.
      RESULTS: Material-specific dissolution parameter values with consequent
      assignment to absorption Types are proposed as well as representative central
      values for the different chemical forms of Am. CONCLUSIONS: The absorption of Am
      oxide is consistent with the moderate absorption Type M while Am nitrate appears
      more soluble. Am associated with plutonium oxide usually follows its slow
      absorption Type S. However, the large variability observed stresses the value of
      investigating the specific absorption kinetics for Am compounds which represent a
      significant risk of internal exposure.

PMID- 24460132
TI  - Cancer stem cell characteristics of circulating tumor cells.
AB  - PURPOSE: To review the results from previous studies aiming at the molecular
      characterization of circulating tumor cells (CTC), to specifically address the
      role of epithelial-mesenchymal-transition (EMT) and stemness features of CTC in
      their contribution to tumor progression and to summarize potential interference
      of CTC with the efficacy of radiotherapy. CONCLUSIONS: Detection of CTC has been
      reported for most epithelial tumors and has been associated with an increased
      risk of local and regional recurrence as well as the development of distant
      metastases. Given a causal relationship between the presence of CTC and tumor
      progression at the primary or distant sites, several distinct features have to be
      postulated for these cells: First, a change from an epithelial to a mesenchymal
      cell-like phenotype which should alleviate the disconnection of individual tumor
      cells from tight cell-to-cell junctions within the epithelial cell layer and
      endow single tumor cells with the capacity to migrate into blood vessels;
      secondly, the presence of stem-cell properties which contribute to the re
      establishment of bulk tumor tissue at the primary or metastatic site upon tumor
      recurrence or distant progression, respectively. Indeed, EMT and stem-cell
      features were frequently observed in CTC and the phenotype of CTC was established
      as a stronger predictor of outcome than sole enumeration of CTC in a defined
      volume of blood. The exploitation of CTC above their use as prognostic marker is
      still a subject of many ongoing investigations as are the identification of
      suitable therapeutic targets for this small cell subpopulation.

PMID- 24460133
TI  - Residential radon exposure and esophageal cancer. An ecological study from an
      area with high indoor radon concentration (Galicia, Spain).
AB  - PURPOSE: To analyze the correlation between municipal esophageal cancer relative
      risk and municipal residential radon concentration in a high radon emission
      Spanish area. MATERIALS AND METHODS: We performed an ecological study at
      municipal level in Galicia, Spain. For each municipality we estimated the median
      radon concentration and the relative risk (RR) for esophageal cancer mortality
      for males and females. The relative risk was calculated using a Bayesian
      approach. Homes with data on radon concentration were selected through stratified
      random sampling. To be included, each municipality had to have at least five
      radon measurements. We obtained Spearman's correlations for median residential
      radon concentration and esophageal cancer mortality RR for males and females,
      separately. RESULTS: We included 129 municipalities, covering the 79% of Galician
      population. 14% of municipalities had radon concentrations above the United
      States Environmental Protection Agency (USEPA) action level. We found a
      statistically significant correlation among residential radon and esophageal
      cancer mortality RR for males (p < 0.001), but not for females. When the analysis
      was restricted to municipalities with more than 15 radon measurements the
      correlation pattern remained. CONCLUSIONS: This is the first study analyzing the
      association between residential radon and esophageal cancer. The results
      suggesting a possible effect of residential radon on esophageal cancer mortality
      should be explored through more robust epidemiological designs such as case
      control studies.

PMID- 24460134
TI  - Enhancement of radiation effectiveness by hyperthermia and incorporation of
      halogenated pyrimidines at low radiation doses as compared with high doses:
      implications for mechanisms.
AB  - PURPOSE: Application of the linear-quadratic (LQ) model for description of
      mammalian cell survival curves to evaluate radiosensitization in dependence on
      dose. METHODS AND MATERIALS: Data on clonogenic assays concerning the combined
      effects of radiation with hyperthermia and halogenated-pyrimidines, were analyzed
      according to the LQ formula for cell survival: S(D)/S(0) = exp-(alphaD+betaD(2)).
      Effects of these agents on the linear parameter alpha and the quadratic parameter
      beta are compared to evaluate differences depending on the applied dose, and the
      possible relations to mechanisms of radiosensitization. RESULTS: The values of
      the linear parameter alpha, which determines the effectiveness at low doses, are
      for most cell lines and in most conditions more increased than the values of the
      parameter beta which has a higher contribution at larger radiation doses. These
      results can be explained by the assumption that the probability of interaction of
      two DNA double-strand breaks (DSB) produced in close proximity by individual
      ionizing particles is more enhanced than interaction of DSB produced at larger
      distances by two separate particles. CONCLUSIONS: The observed differences
      between values of alpha and beta imply that the radiation enhancement factors are
      larger at low doses mostly applied in clinical radiotherapy as compared with
      larger doses as mostly evaluated in experimental studies.

PMID- 24460135
TI  - Mapping affected territory of anterior/posterior inferior cerebellar artery
      infarction using a vestibular test battery.
AB  - CONCLUSION: Although the affected territory in the posterior/anterior inferior
      cerebellar artery (PICA/AICA) infarction could not be meticulously demonstrated
      by magnetic resonance imaging (MRI), it could be picked up by the results of a
      vestibular test battery comprising caloric, ocular vestibular evoked myogenic
      potential (oVEMP), and cervical VEMP (cVEMP) tests. OBJECTIVES: This study
      applied audiometry and caloric, oVEMP, and cVEMP tests to map affected territory
      in patients with PICA/AICA infarction. METHODS: Fourteen patients, including 11
      with PICA infarction and 3 with AICA infarction, were enrolled in this study
      during the last 8 years. Each patient underwent audiometry, caloric test, oVEMP
      test, and cVEMP test. RESULTS: In the PICA group, 8 (36%) of 22 ears had a mean
      hearing level >25 dB. All six ears (100%) in the AICA group had abnormal hearing,
      and thus both groups revealed a significant difference. Conversely, significant
      differences were not observed in the vestibular test battery between the PICA and
      AICA groups. MRI demonstrated infarction at the brainstem for six patients, while
      one patient also had cerebellar involvement, indicated by loss of visual
      suppression on caloric nystagmus. Six patients showed infarction at the
      cerebellum, and four of them had brainstem affliction based on abnormal
      oVEMP/cVEMP test results.

PMID- 24460136
TI  - Evidence of highly active cobalt oxide catalyst for the Fischer-Tropsch synthesis
      and CO2 hydrogenation.
AB  - Hydrogenations of CO or CO2 are important catalytic reactions as they are
      interesting alternatives to produce fine chemical feedstock hence avoiding the
      use of fossil sources. Using monodisperse nanoparticle (NP) catalysts, we have
      studied the CO/H2 (i.e., Fischer-Tropsch synthesis) and CO2/H2 reactions.
      Exploiting synchrotron based in situ characterization techniques such as XANES
      and XPS, we were able to demonstrate that 10 nm Co NPs cannot be reduced at 250 
      degrees C while supported on TiO2 or SiO2 and that the complete reduction of
      cobalt can only be achieved at 450  degrees C. Interestingly, cobalt oxide
      performs better than fully reduced cobalt when supported on TiO2. In fact, the
      catalytic results indicate an enhancement of 10-fold for the CO2/H2 reaction rate
      and 2-fold for the CO/H2 reaction rate for the Co/TiO2 treated at 250  degrees C
      in H2 versus Co/TiO2 treated at 450  degrees C. Inversely, the activity of cobalt
      supported on SiO2 has a higher turnover frequency when cobalt is metallic. The
      product distributions could be tuned depending on the support and the oxidation
      state of cobalt. For oxidized cobalt on TiO2, we observed an increase of methane
      production for the CO2/H2 reaction whereas it is more selective to unsaturated
      products for the CO/H2 reaction. In situ investigation of the catalysts indicated
      wetting of the TiO2 support by CoO(x) and partial encapsulation of metallic Co by
      TiO(2-x).

PMID- 24460139
TI  - Graphene quantum dots as fluorescence probes for turn-off sensing of melamine in
      the presence of Hg(2+).
AB  - A rapid and sensitive fluorescence sensing system for melamine based on charge
      transfer quenching of the fluorescence of graphene quantum dots (GQDs) in the
      presence of Hg(2+) is proposed. The synthesized GQDs were strongly luminescent
      with predominantly aromatic sp(2) domains. Melamine could coordinate with mercury
      through nitrogen atoms in both its amine and triazine groups and bring more
      Hg(2+) to the surface of GQDs through pi-pi stacking, thus leading to quenching
      of the GQDs' fluorescence. The quenching mechanism was investigated in detail and
      ascribed to charge transfer from the GQDs to Hg(2+) with melamine acting as the
      linkage agent. The melamine demonstrated a linear range 0.15-20 MUM and a
      detection limit of 0.12 MUM, which was far below the regulatory level, suggesting
      the promising practical usage of this sensing system. This sensing system also
      possessed high selectivity for melamine in the presence of possible
      interferences. Finally, this novel sensor was successfully applied for melamine
      detection in raw milk and satisfactory recovery was achieved. 

PMID- 24460140
TI  - Multiple e-pharmacophore modeling, 3D-QSAR, and high-throughput virtual screening
      of hepatitis C virus NS5B polymerase inhibitors.
AB  - The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRP) is a crucial
      and unique component of the HCV RNA replication machinery and a validated target
      for drug discovery. Multiple crystal structures of NS5B inhibitor complexes have
      facilitated the identification of novel compound scaffolds through in silico
      analysis. With the goal of discovering new NS5B inhibitor leads, HCV NS5B crystal
      structures bound with inhibitors in the palm and thumb allosteric pockets in
      combination with ligands with known inhibitory potential were explored for a
      comparative pharmacophore analyses. The energy-based and 3D-QSAR-based
      pharmacophore models were validated using enrichment analysis, and the six models
      thus developed were employed for high-throughput virtual screening and docking to
      identify nonpeptidic leads. The hits derived at each stage were analyzed for
      diversity based on the six pharmacophore models, followed by molecular docking
      and filtering based on their interaction with amino acids in the NS5B allosteric
      pocket and 3D-QSAR predictions. The resulting 10 hits displaying diverse scaffold
      were then screened employing biochemical and cell-based NS5B and anti-HCV
      inhibition assays. Of these, two molecules H-5 and H-6 were the most promising,
      exhibiting IC50 values of 28.8 and 47.3 MUM against NS5B polymerase and anti-HCV
      inhibition of 96% and 86% at 50 MUM, respectively. The identified leads comprised
      of benzimidazole (H-5) and pyridine (H-6) scaffolds thus constitute prototypical
      molecules for further optimization and development as NS5B inhibitors. 

PMID- 24460143
TI  - Factors associated with prevention of postural hypotension by leg compression
      bandaging.
AB  - AIM: We evaluated the eventual effects of leg compression on seating-induced
      postural hypotension (PH) in the context of various relevant clinical variables.
      METHODS: Included were 73 hospitalized patients with various acute conditions,
      aged >= 60 years, bedridden for >= 8 h, with diagnosed PH [>= 20 mmHg systolic
      and/or >= 10 mmHg diastolic blood pressure (BP) falls] at the first seating. BP,
      heart rhythm, dizziness and palpitations were recorded before and during 5 min of
      sitting. The next day, the patients were reevaluated, this time using compression
      bandages applied along both legs before seating. RESULTS: Compared with the non
      bandaged state, PH was registered in only 53% of bandaged patients (p < 0.001).
      Moreover, the appearance of PH symptoms decreased (p < 0.001). On the second day
      (bandaged), supine diastolic BP values were higher in the persisting vs non
      persisting PH group (p = 0.027). In the bandaged state, PH symptoms were
      significantly reduced in the non-persisting PH group (p = 0.003). Even in
      patients with persistent PH, the magnitude of BP decline and appearance of PH
      symptoms were decreased while wearing bandages (p = 0.004 and 0.002,
      respectively). CONCLUSION: During mobilization of inpatients, leg compression
      seems to reduce the seating-induced PH and relevant symptoms. Even in patients
      with persisting PH, bandaging may improve hemodynamics and attenuate associated
      symptoms.

PMID- 24460144
TI  - Nanodynamics of dendritic core-multishell nanocarriers.
AB  - The molecular dynamics of polymeric nanocarriers is an important parameter for
      controlling the interaction of nanocarrier branches with cargo. Understanding the
      interplay of dendritic polymer dynamics, temperature, and cargo molecule
      interactions should provide valuable new insight for tailoring the dendritic
      architecture to specific needs in nanomedicine, drug, dye, and gene delivery.
      Here, we have investigated polyglycerol-based core-multishell (CMS)
      nanotransporters with incorporated Nile Red as a fluorescent drug mimetic and CMS
      nanotransporters with a covalently bound fluorophore (Indocarbocyanine) using
      fluorescence spectroscopy methods. From time-resolved fluorescence depolarization
      we have obtained the rotational diffusion dynamics of the incorporated dye, the
      nanocarrier, and its branches as a function of temperature. UV/vis and
      fluorescence lifetime measurements provided additional information on the local
      dye environment. Our results show a distribution of the cargo Nile Red within the
      nanotransporter shells that depends on solvent and temperature. In particular, we
      show that the flexibility of the polymer branches in the unimolecular state of
      the nanotransporter undergoes a temperature-dependent transition which correlates
      with a larger space for the mobility of the incorporated hydrophobic drug mimetic
      Nile Red and a higher probability of cargo-solvent interactions at temperatures
      above 31  degrees C. The measurements have further revealed that a loss of the
      cargo molecule Nile Red occurred neither upon dilution of the CMS
      nanotransporters nor upon heating. Thus, the unimolecular preloaded CMS
      nanotransporters retain their cargo and are capable to transport and respond to
      temperature, thereby fulfilling important requirements for biomedical
      applications. 

PMID- 24460145
TI  - Enhancing photocatalytic activity of LaTiO2N by removal of surface reconstruction
      layer.
AB  - LaTiO2N is an oxynitride photocatalyst that has ability to generate H2 and O2
      from water under irradiation of light with wavelengths up to 600 nm. However,
      LaTiO2N necessitates sacrificial reagents that capture either photoexcited
      electrons or holes efficiently to be active in the photocatalytic reactions
      because of a considerable number of defects that cause trapping and recombination
      of photoexcited carriers. Therefore, identifying defect structures of LaTiO2N is
      important. In this study, using atomic-resolution scanning transmission electron
      microscopy, we evidence that eliminating defective surface reconstructed layers
      of LaTiO2N particles by the treatment with aqua regia can double the
      photocatalytic activity. 

PMID- 24460146
TI  - Promotion and tenure.

PMID- 24460149
TI  - Biomechanical behaviour of cancellous bone on patellofemoral arthroplasty with
      Journey prosthesis: a finite element study.
AB  - Isolated patellofemoral (PF) arthritis of the knee is a common cause of anterior
      knee pain and disability. Patellofemoral arthroplasty (PFA) is a bone conserving
      solution for patients with PF degeneration. Failure mechanisms of PFA include
      growing tibiofemoral arthritis and loosening of components. The implant loosening
      can be associated with bone resorption or fatigue-failure of bone by overload.
      This research work aims at determining the structural effects of the implantation
      of PF prosthesis Journey PFJ (Smith & Nephew, Inc., Memphis, TN, USA) on femoral
      cancellous bone. For this purpose, the finite element method is considered to
      perform computational simulations for different conditions, such as well-fixed
      and loosening scenarios. From the global results obtained, in the well-fixed
      scenario, a decrease in strain on cancellous bone was noticed, which can be
      related to bone resorption. In the loosening scenario, when the cement layer
      becomes inefficient, a significant increase in cancellous bone strain was
      observed, which can be associated with bone fatigue-failure.These strain changes
      suggest a weakness of the femur after PFA.

PMID- 24460147
TI  - Ion permeability of the nuclear pore complex and ion-induced macromolecular
      permeation as studied by scanning electrochemical and fluorescence microscopy.
AB  - Efficient delivery of therapeutic macromolecules and nanomaterials into the
      nucleus is imperative for gene therapy and nanomedicine. Nucleocytoplasmic
      molecular transport, however, is tightly regulated by the nuclear pore complex
      (NPC) with the hydrophobic transport barriers based on phenylalanine and glycine
      repeats. Herein, we apply scanning electrochemical microscopy (SECM) to
      quantitatively study the permeability of the NPCs to small probe ions with a wide
      range of hydrophobicity as a measure of their hydrophobic interactions with the
      transport barriers. Amperometric detection of the redox-inactive probe ions is
      enabled by using the ion-selective SECM tips based on the micropipet- or
      nanopipet-supported interfaces between two immiscible electrolyte solutions. The
      remarkably high ion permeability of the NPCs is successfully measured by SECM and
      theoretically analyzed. This analysis demonstrates that the ion permeability of
      the NPCs is determined by the dimensions and density of the nanopores without a
      significant effect of the transport barriers on the transported ions.
      Importantly, the weak ion-barrier interactions become significant at sufficiently
      high concentrations of extremely hydrophobic ions, i.e., tetraphenylarsonium and
      perfluorobutylsulfonate, to permeabilize the NPCs to naturally impermeable
      macromolecules. Dependence of ion-induced permeabilization of the NPC on the
      pathway and mode of macromolecular transport is studied by using fluorescence
      microscopy to obtain deeper insights into the gating mechanism of the NPC as the
      basis of a new transport model. 

PMID- 24460150
TI  - Subnanometer vacancy defects introduced on graphene by oxygen gas.
AB  - The basal plane of graphene has been known to be less reactive than the edges,
      but some studies observed vacancies in the basal plane after reaction with oxygen
      gas. Observation of these vacancies has typically been limited to nanometer-scale
      resolution using microscopic techniques. This work demonstrates the introduction
      and observation of subnanometer vacancies in the basal plane of graphene by heat
      treatment in a flow of oxygen gas at low temperature such as 533 K or lower. High
      resolution transmission electron microscopy was used to directly observe vacancy
      structures, which were compared with image simulations. These proposed structures
      contain C?O, pyran-like ether, and lactone-like groups. 

PMID- 24460151
TI  - Evaluation of a bedside test of utricular function - the bucket test - in older
      individuals.
AB  - CONCLUSION: As a bedside test of subjective visual vertical (SVV), the 'bucket
      test' has a role as a viable and cost-effective clinical test of unilateral
      utricular dysfunction in older individuals. OBJECTIVE: To investigate whether the
      bucket test as a test of the SVV is a valid bedside test of utricular function in
      older individuals. METHODS: This was a diagnostic validation study at a tertiary
      academic medical center. Vestibular function was evaluated using sound-evoked
      cervical and tap-evoked ocular vestibular evoked myogenic potential (cVEMP and
      oVEMP, respectively) asymmetry ratios, the bucket test of SVV, and the Dizziness
      Handicap Index (DHI), in 51 older individuals aged 70-95 years. RESULTS: Bucket
      test scores are correlated in both magnitude and direction with utricle-selective
      tap-evoked oVEMP asymmetry ratios, but not with sound-evoked cVEMP asymmetry
      ratios, which are saccule-selective, or with the DHI. Receiver operating
      characteristics analysis suggests that the bucket test is more specific than
      sensitive for utricular dysfunction, and a bucket test SVV score of 2 degrees 
      may maximize diagnostic yield relative to the currently accepted score of 3.

PMID- 24460152
TI  - Effectiveness of the leukotriene receptor antagonist pranlukast hydrate for the
      treatment of sleep disorder in patients with perennial allergic rhinitis.
AB  - CONCLUSION: We found that addition of pranlukast to the conventional treatment
      for perennial allergic rhinitis may contribute to improvements in sleep disorder
      symptoms through a decrease in nasal congestion. OBJECTIVE: We aimed to determine
      whether the leukotriene receptor antagonist pranlukast hydrate is effective in
      treating sleep disorder in patients with perennial allergic rhinitis. METHODS: We
      conducted a questionnaire survey to determine the symptoms of rhinitis and sleep
      disturbances in 48 adult patients with perennial allergic rhinitis who visited
      the outpatient otolaryngology departments in hospitals in Yamaguchi Prefecture,
      Japan. The subjects presented with nasal symptoms and symptoms of sleep disorder
      during the last 2 weeks of treatment for allergic rhinitis that lasted for at
      least 1 month. A questionnaire based on the Pittsburgh Sleep Quality Index and
      Athens Insomnia Scale with some modifications was administered before and 4 weeks
      after the addition of pranlukast to the conventional treatment. RESULTS: Addition
      of pranlukast improved the symptoms of perennial allergic rhinitis, with
      responses to all items of the questionnaire administered 4 weeks after pranlukast
      addition indicating significant improvements. Furthermore, the improvement in
      sleep disorder symptoms significantly correlated with improvement in nasal
      congestion, but not with improvements in sneezing and nasal discharge.

PMID- 24460153
TI  - The oncoprotein, gankyrin, is up-regulated in middle ear cholesteatoma.
AB  - CONCLUSION: Gankyrin seems to be a better biomarker for cholesteatoma compared
      with Ki-67. OBJECTIVE: Gankyrin is an oncoprotein, and occurs in cancers but not
      in benign diseases. The goal of this study was to compare expression of gankyrin,
      p53, and a proliferation marker (Ki-67) in cholesteatoma and retroauricular skin
      (RAS), and to evaluate their significance as clinical parameters. METHODS: The
      levels of expression of gankyrin, Ki-67, and p53 in 10 cholesteatoma and 10
      paired samples of normal RAS were evaluated by immunohistochemical staining and
      Western blot. The results were compared with clinical profiles to investigate a
      correlation. RESULTS: The expression of gankyrin, Ki-67, and p53 proteins was
      observed in both basal and suprabasal layers of cholesteatoma. The intensity of
      gankyrin expression was 'positive' in two cases (20%) and 'strongly positive' in
      eight cases (80%); p53 expression in the suprabasal layer was 'positive' in 70%
      of cases; and the Ki-67 staining was 'focal' in 80% of cases. In RAS, these
      proteins were expressed dominantly in the basal layer. Western blot analysis
      showed that the gankyrin band was more intense in cholesteatoma than in RAS for
      three of four cases (p < 0.05). However, there was no significant difference in
      the expression of gankyrin, Ki-67, and p53 according to clinical variables.

PMID- 24460154
TI  - Localization of sirtuins in the mouse inner ear.
AB  - CONCLUSION: It is suggested that SIRT1 and 3, and probably SIRT4 and 5, play an
      important role in the neuroprotection of the inner ear. SIRT2 may be related to
      neuroprotection and myelin sheath formation, while SIRT6 seems to have a
      significant role in maintaining the energy balance by metabolic regulation.
      OBJECTIVE: To analyze the expression of sirtuins (SIRT1-7) in the normal mouse
      inner ear. METHODS: CBA/J mice were used for this study. The localization of
      SIRT1-7 in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic
      sac, was investigated using real-time PCR and immunohistochemistry. RESULTS: We
      found high levels of mRNA of all seven sirtuins in the inner ear. In the
      immunohistochemical study, SIRT1-7 were abundant in many inner ear structures,
      i.e. stria vascularis, inner and outer hair cells, spiral ganglion cells,
      vestibular sensory and ganglion cells, vestibular dark and transitional cells,
      and the endolymphatic sac.

PMID- 24460155
TI  - Changes in electrical response function and myosin heavy chain isoforms following
      denervation and reinnervation of bilateral posterior cricoarytenoid muscles in
      dogs.
AB  - CONCLUSIONS: Both electrical response function and mRNA expression of myosin
      heavy chain (MyHC) types 2X, 1, and Neonatal of bilateral posterior
      cricoarytenoid (PCA) muscle changed after denervation or reinnervation in
      canines. OBJECTIVES: There is a need to investigate the electrical response
      function MyHC alteration of denervation or reinnervation in the bilateral PCA
      muscle of large animals. METHODS: MyHC isoforms expression profile and PCA muscle
      function outcome were detected by real-time reverse transcribed-polymerase chain
      reaction and muscle response to functional electrical stimulation, 9 weeks after
      denervation and reinnervation with ansa-recurrent laryngeal nerve anastomosis in
      dogs. RESULTS: Denervation produced up-regulation of MyHC-1 and MyHC-Neonatal
      messenger ribonucleic acid (mRNA) expression. Reinnervation caused a decrease of
      MyHC-2X mRNA expression. The electrical voltage threshold of vocal fold movement
      and maximum abduction of denervation were greater than that of the reinnervated
      or control group. The denervated vocal abduction maximum of response to
      electrical stimulation was less than that in reinnervation or control groups.

PMID- 24460156
TI  - The complete mitochondrial genome of Leuciscus leuciscus baicalensis
      (Cypriniformes: Cyprinidae).
AB  - The complete mitochondrial genome of Leuciscus leuciscus baicalensis was cloned
      and sequenced in the present study. The genome which had a mostly conserved
      structural organization in comparison with that of other teleost fish was 16,606
      bp in size. It consisted of 37 genes (13 protein-coding genes, 22 transfer RNA
      genes and 2 ribosomal RNA genes), and 2 main non-coding regions (the control
      region and the origin of the light strand replication). All protein-coding genes
      started with ATG except for COX 1, which began with GTG. However, the termination
      codons of 13 protein-coding genes varied with TAA, TA, T or TAG. The complete
      mitochondrial genome sequence provided useful information for phylogenetic
      analysis and studies of population genetics of L. leuciscus baicalensis.

PMID- 24460157
TI  - Mitochondrial genome of a flashwing demoiselle, Vestalis melania from the
      Philippine Archipelago.
AB  - This study determined the first complete mitochondrial genome of a demoiselle,
      Vestalis melania (Odonata, Zygoptera, Calopterygidae) using long-range PCR and a
      primer walking approach. This mitogenome is 16,685 bp long and contains the
      entire set of 37 genes and an A + T-rich control region typically found in
      insects. Presently, this mitogenome is the largest mitogenome of all available
      odonates, mainly because of its long A + T-rich region (2036 bp). The gene
      arrangement of the V. melania mitogenome is identical to that of other known
      odonates. The inter-genic spacer s5 shared by the Anisoptera is absent in V.
      melania, which supports the view that the absence of the s5 spacer is a
      synapomorphy of the Zygoptera.

PMID- 24460158
TI  - The complete mitochondrial genome sequence of Hemiculter leucisculus.
AB  - The complete mitochondrial genome of Hemiculter leucisculus was determined to be
      16,617 bp. It contains the structure of 22 transfer RNA genes, 13 protein-coding
      genes, 2 ribosomal RNA genes, and non-coding control region (D-loop). The
      critical central conserved sequences (CSB-D, CSB-E, and CSB-F) were also
      detected. The determination of H. leucisculus mitogenome would play an important
      role in genetic diversity and population vitality in Cyprinidae.

PMID- 24460159
TI  - The complete mitochondrial genome of the duskytail grouper Epinephelus bleekeri
      (Serranidae: Epinephelinae).
AB  - The complete mitochondrial genome of Epinephelus bleekeri was first presented in
      this study. It is 17,227 bp in length, consisted of 13 protein-coding genes, 22
      tRNA genes, 2 rRNA genes and a non-coding control region. The overall base
      composition of the H-strand is 26.32% A, 28.65% T, 28.72% G and 16.31% C. With
      the exception of ND6 and eight tRNA genes, all other mitochondrial genes are
      encoded on the heavy strand. In particular, gene duplication is found on the tRNA
      Asp gene, and five tandem repeat of this gene in E. bleekeri is different from
      most other vertebrates. The control region is rich in A + T (67.12%) and poor in
      G (14.00%), and tandem repeat sequences are observed in this non-coding region,
      indicating a useful marker for population genetic studies.

PMID- 24460161
TI  - Global haplotype analysis of the whitefly Bemisia tabaci cryptic species Asia I
      in Asia.
AB  - The whitefly, Bemisia tabaci (Hemiptera: Aleyrodidiae), is a cryptic species
      complex comprising a minimum of 24 cryptic species. Some members of this complex
      are important agricultural pests, causing considerable damage to vegetable as
      well as ornamental and horticultural crops. Asia I, one of the cryptic species of
      B. tabaci, is widely distributed in Asia. One hundred and sixty mitochondrial
      cytochrome oxidase I (COI) sequences from eight countries have been analyzed to
      investigate the geographic origin and current genetic structure of this cryptic
      species. Sixty different haplotypes were identified, with levels of genetic
      distances ranging from 0.001 to 0.021. A sign of possible genetic differentiation
      emerges from the differential distribution of dominant haplotypes in Indonesia
      and India compared to China. A possible ancient separation between Asia I in
      India and Indonesia and secondary contact in China has been hypothesized. 

PMID- 24460160
TI  - Degradation of mitochondrial DNA in cryoprotectant-treated hard coral (Echinopora
      spp.) oocytes.
AB  - A critical step for successful cryopreservation is to determine the optimal
      cryoprotectant treatment that can provide protective effects against cryoinjury
      during freezing and with minimal toxicity. Most cryoprotectants have chemical and
      osmotic effects when used at high concentrations. Cryoprotectants can damage
      coral mitochondrial distributions and membrane potentials, which results in
      reduced ATP production. As mitochondrial DNA (mtDNA) encodes for components of
      the electron transport chain (ETC) and plays a critical role in ATP synthesis
      capacity, we determined the effects of cryoprotectants on mtDNA in hard coral
      (Echinopora spp.) oocytes using quantitative real-time PCR. Our results showed
      that an insult from a cryoprotectant may be compensated for by the genetic
      defense mechanisms of these cells. Methanol was found to have the least effect on
      coral oocytes with regard to their energy status. A single oocyte without
      cryoprotectant treatment produced an average of 4,220,645 +/- 169,990 mtDNA
      copies, which was greater than that in mammals. However, relatively lower mtDNA
      copy numbers (<2,000,000) were observed when oocytes were treated with dimethyl
      sulfoxide (DMSO), propylene glycol (PG), ethylene glycol (EG), or glycerol at a
      concentration of 3 M for 20 min. These results provide direct evidence that hard
      coral (Echinopora spp.) oocytes are extremely susceptible to cryoprotectants and
      support the concerns with regard to the adverse effects of cryoprotectants. 

PMID- 24460162
TI  - The complete mitochondrial genome of Clarias fuscus (Teleostei, Siluriformes:
      Clariidae).
AB  - The Clarias fuscus is an important economic fish in China and distributed widely
      in south China, e.g. Yangtze river, Pearl River, and Min River, even Hainan
      island. It is also distributed in Southeast Asia and Africa, so it is a good
      model for study population genetics and geological changes of these region. In
      this study, the complete mitochondrial genome sequence of C. fuscus has been
      obtained with PCR. The gene composition and arrangement of mitochondrial genome
      sequence of C. fuscus are similar to most of other vertebrates, which contains 13
      protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a non-coding control
      region with total length of 16,518 bp. Most of genes are encoded on Heavy-Strand
      (H-strand), except for eight tRNA and ND6 genes. Like most vertebrates, the bias
      of G and C has universality in different region (genes). The complete
      mitochondrial genome sequence of C. fuscus would contribute for better
      understanding of population genetics, conservation, biogeography, evolution of
      this species.

PMID- 24460163
TI  - The complete mitochondrial genome of Parara guttata (Lepidoptera: Hesperiidae).
AB  - The mitochondrial genome (mitogenome) of Parara guttata (Hesperiidae:
      Hesperiinae) is a circular molecule of 15,441 bp in length, containing 37 typical
      animal mitochondrial genes: 13 protein-coding genes (PCGs), 2 ribosomal RNAs, 22
      transfer RNAs and a non-coding AT-rich region. Its gene order and arrangement are
      identical to the common type found in most lepidopteran mitogenomes. All PCGs
      start with a typical ATN codon except for COI and ND1 which use CGA and GTG as
      their start codons, respectively. Some PCGs harbor TAG (ND1) or incomplete
      termination codon T (COI, COII, ND5, ND4), while others use standard TAA as their
      termination codons. The 411-bp long AT-rich region contains a conserved motif
      ATAGA followed by a 19-bp poly-T stretch and a microsatellite-like (TA)5 element
      preceded by the ATTTA motif.

PMID- 24460164
TI  - Complete mitochondrial genome of the pacific seahorse Hippocampus ingens Girard,
      1858 (Gasterosteiformes: Syngnathidae).
AB  - The complete mitochondrial genome sequence of the pacific seahorse Hippocampus
      ingens was determined using long polymerase chain reactions. The total length of
      H. ingens mitogenome is 16,526 bp and consists of 13 protein-coding genes, 2 rRNA
      genes, 22 tRNA genes and a control region. The gene order and composition of H.
      ingens were similar to those of most other vertebrates. The overall base
      composition of H. ingens is 32.6% A, 29.3% T, 23.5% G and 14.6% C, with a slight
      A+T rich feature (61.9%).

PMID- 24460165
TI  - Complete mitochondrial genome of Germain's Peacock-Pheasant Polyplectron germaini
      (Aves, Galliformes, Phasianidae).
AB  - The Germain's Peacock-Pheasant Polyplectron germaini (Aves, Galliformes,
      Phasianidae) is classified as Near Threatened on the IUCN Red List. The complete
      mitochondrial genome of P. germaini is 16,699 bp, consisting of 13 protein-coding
      genes, 2 rRNA, 22 tRNA genes and 1 control region. All of the 13 protein-coding
      genes have ATG as start codon. Eight of the 13 protein-coding genes have TAA as
      stop codon.

PMID- 24460166
TI  - Complete mitochondrial genome of Peronia verruculata (Gastropoda: Pulmonata:
      Systellommatophora: Onchidiidae).
AB  - The complete mitochondrial genome sequence of Peronia verruculata is firstly
      described in the article. The mitogenome (13,861 bp) contains 22 tRNA genes, 2
      ribosomal RNA genes and 13 protein-coding genes. The characteristic is the
      typical bivalvia mitochondrial gene composition.

PMID- 24460167
TI  - The complete mitochondrial genome of Liachirus melanospilos (Pleuronectiformes:
      Soleidae).
AB  - Liachirus melanospilos (Pleuronectiformes: Soleidae) is characterized by both
      eyes on the right side of the body and pale brown color with black dots, small
      irregular, brown spots and large vague ocelli. In this study, the complete
      mitogenome sequence of this carpet sole has been determined. The total length is
      17,001 bp, including 13 protein-coding genes, 22 tRNA genes and 2 rRNA genes (12S
      and 16S), as well as one control region and one L-strand replication origin (OL).
      Gene contents, locations and arrangements are identical to those of typical bony
      fishes. The nucleotide composition of the genome is 30.9%, 27.8%, 15.9% and 25.5%
      for A, C, G and T, respectively, with a slight bias of A + T content (56.4%). The
      determination of L. melanospilos complete mitogenome sequence could contribute to
      a better understanding of the systematic evolution of Soleidae and
      Pleuronectiformes.

PMID- 24460168
TI  - The complete mitochondrial genome of Hainanese barbel steed Hemibarbus medius Yue
      (Teleostei: Cyprinidae).
AB  - In this study, the complete mitogenome sequence of cyprinid fish, Hainanese
      barbel steed, Hemibarbus medius Yue (Teleostei: Cyprinidae) has been amplified
      and sequenced by employing long polymerase chain reaction method. The mitogenome,
      consisting of 16,614 base pairs (bp), had the typical vertebrate mitochondrial
      gene arrangement, including 13 protein-coding genes, 22 transfer RNAs, 2
      ribosomal RNAs genes and a non-coding control region (CR). CR of 933 bp length is
      located between tRNA(Pro) and tRNA(Phe). The overall base composition of
      Hemibarbus medius is 29.8% for A, 27.2% for C, 25.9% for T and 17.1% for G, with
      a slight AT bias of 55.7%. The complete mitogenome may provide rather essential
      and important DNA molecular data for further phylogenetic analysis for not only
      congeneric species but also higher different taxa of Cyprinid fishes.

PMID- 24460169
TI  - The complete mitochondrial genome of the sand tiger shark, Carcharias taurus
      (Chondrichthyes, Odontaspididae).
AB  - The complete mitochondrial genome of the sand tiger shark consists of 16,773 bp
      and including 13 protein-coding genes, 2 ribosomal RNA, 22 transfer RNA genes, 1
      replication origin region and 1 control region. The mitochondrial gene
      arrangement of the sand tiger shark is the same as the one observed in most
      vertebrates. Base composition of the genome is A (31.8%), T (28.7%), C (26.3%)
      and G (13.2%).

PMID- 24460170
TI  - Mitochondrial genome of the spot-tail shark Carcharhinus sorrah
      (Carcharhiniformes: Carcharhinidae).
AB  - In this article, we first presented the complete mitogenome of the spot-tail
      shark Carcharhinus sorrah, which is a medium-sized shark distributed in the
      tropical Indo-Pacific and is currently listed as "Near Threatened" on the
      International Union for Conservation of Nature (IUCN) Red List. The complete
      mitogenome of C. sorrah is 16,707 bp in length and contains typical 37 genes and
      one control region. The overall base composition is 31.4% A, 25.8% C, 13.2% G and
      29.6% T. The control region is 1066 bp in length with the highest A + T content
      (66.8%) and lowest G content (13.2%).

PMID- 24460171
TI  - Complete mitochondrial genome of the Easten hulafish, Trachinops taeniatus
      (Perciformes: Plesiopidae).
AB  - The first complete mitochondrial genome (mitogenome) of Plesiopidae (Teleostei:
      Perciformes) was determined using the Eastern hulafish Trachinops taeniatus as a
      representative species of the family. The mitogenome was 16,821 bp in length,
      including 13 typical vertebrate protein-coding genes, 22 transfer RNA genes, 2
      ribosomal RNA genes and 1 control region. The gene arrangement was similar to
      other fishes except for the reversal position of tRNA(Ala) and tRNA(Asn). The
      overall base composition was 27.4% for A, 27.5% for C, 27.4% for T and 17.7% for
      G. This mitogenome should contribute to resolving phylogenetic position of
      Plesiopidae.

PMID- 24460172
TI  - An effective strategy for species identification of avian meats using the
      mitochondrial 12S rRNA gene fragment.
AB  - An effective DNA-based molecular method had been used to identify avian species
      from meats. The method combined the use of a pair of universal primers, which
      amplified about 440-bp fragment of the mitochondrial 12S rRNA gene. A total of 99
      meat samples were tested and 17 haplotypes were identified by DNA sequencing,
      which representing 14 avian species. One avian species was listed as the national
      first-grade protected animal in China and the IUCN endangered species. Two avian
      species were under the national second-grade state protection. The proposed
      method represents a straightforward and robust method for the accurate
      identification of avian species that could be used by law enforcement agencies as
      a tool for the control of illegal trade of meat from protected species. 

PMID- 24460173
TI  - Mitochondrial DNA sequence of Onychostoma rara.
AB  - The complete mitochondrial genome sequence of Onychostoma rara was determined to
      be 16,590 bp in length and contains 13 protein-coding genes (PCGs), 22 tRNA
      genes, large (rrnL) and small (rrnS) rRNA and the non-coding control region. Its
      total A + T content is 55.65%. We also analyzed the structure of control region,
      6 CSBs (CSB-1, CSB-2, CSB-3, CSB-D, CSB-E and CSB-F) and 2 bp tandem repeat were
      detected.

PMID- 24460174
TI  - Skeletal muscle mass, bone mineral density, and walking performance in masters
      cyclists.
AB  - Exercise mode and intensity/duration are important factors for influencing muscle
      morphology and function as well as bone. However, it is unknown whether masters
      cyclists who undergo regular moderate- to high-intensity exercise maintain lower
      body skeletal muscle mass (SM) and function and bone health when compared with
      young adults. The purpose of this study was to compare SM, areal bone mineral
      density (aBMD), and gait performance between masters cyclists and young adults.
      Fourteen male masters cyclists (aged 53-71 years) and 13 moderately active young
      men (aged 20-30 years, exercising less than twice a week) volunteered. The
      masters cyclists were all training actively (four to five times per week, ~200
      miles per week) for on average the last 17 years (range 7-38 years). Thigh SM was
      estimated from an ultrasound-derived prediction equation using muscle thickness
      (MTH). Appendicular lean mass (aLM) and aBMD were also estimated using dual
      energy X-ray absorptiometry. There were no significant differences (p<0.05) in
      thigh SM, anterior and posterior thigh MTH ratio, or aLM between masters cyclists
      and young men. Maximum straight and zigzag walking times were also similar
      between groups. Lumbar spine (L1-L4) aBMD was not different between groups, but
      femoral neck aBMD was lower (p<0.05) in the cyclists than in the young men. Our
      results suggest that appendicular as well as site-specific thigh muscle loss with
      aging were not observed in masters cyclists. This maintenance of muscle mass in
      masters cyclists may preserve walking performance to similar levels as moderately
      active young adults. However, long-term cycling does not preserve femoral neck
      aBMD.

PMID- 24460175
TI  - Controlled release of protein from biodegradable multi-sensitive injectable
      poly(ether-urethane) hydrogel.
AB  - The synthesis and characterization of multi-sensitive polymers for use as
      injectable hydrogels for controlled protein/drug delivery is reported. A series
      of biodegradable multi-sensitive poly(ether-urethane)s were prepared through a
      simple one-pot condensation of poly(ethylene glycol), 2,2'-dithiodiethanol, N
      methyldiethanolamine, and hexamethylene diisocyanate. The sol-gel phase
      transition behaviors of the obtained copolymers were investigated. Experimental
      results showed that the aqueous medium comprising the multi-segment copolymers
      underwent a sol-to-gel phase transition with increasing temperature and pH. At a
      certain concentration, the copolymer solution could immediately change to a gel
      under physiological conditions (37  degrees C and pH 7.4), indicating their
      suitability as in situ injectable hydrogels in vivo. Insulin was used as a model
      protein drug for evaluation of the injectable hydrogels as a site-specific drug
      delivery system. The controlled release of insulin from the hydrogel devices was
      demonstrated by degradation of the copolymer, which is modulated via the 2,2'
      dithiodiethanol content in the poly(ether-urethane)s. These hydrogels having
      multi-responsive properties may prove to be promising candidates for injectable
      and controllable protein drug delivery devices. 

PMID- 24460176
TI  - Correction to Synthesis and Properties of the Cyano Complex of Oxo-Centered
      Triruthenium Core [Ru3(MU3-O)(MU-CH3COO)6(pyridine)2(CN)].

PMID- 24460178
TI  - Biomarkers of eosinophilic inflammation in asthma.
AB  - Eosinophils are mediators of allergic inflammation and are implicated in the
      pathogenesis of numerous conditions including asthma, parasitic infections,
      neoplasms, hyper-eosinophilic syndromes, vasculitic disorders, and organ-specific
      conditions. Assessing eosinophilic inflammation is therefore important in
      establishing a diagnosis, in monitoring and assessing response to treatment, and
      in testing novel therapeutics. Clinical markers of atopy and eosinophilic
      inflammation include indirect tests such as lung function, exhaled breath
      condensate analysis, fractional exhaled nitric oxide, serum immunoglobulin E
      levels and serum periostin. Direct measures, which quantify but do not
      anatomically localise inflammation include blood eosinophil counts, serum or
      plasma eosinophil cationic protein and sputum eosinophil levels. Cytology from
      bronchoalveolar lavage and histology from endobronchial and transbronchial
      biopsies are better at localising inflammation but are more invasive. Novel
      approaches using radiolabelled eosinophils with single-photon emission computed
      tomography, offer the prospect of non-invasive methods to localise eosinophilic
      inflammation. 

PMID- 24460179
TI  - Bicelles exhibiting magnetic alignment for a broader range of temperatures: a
      solid-state NMR study.
AB  - Bicelles are increasingly used as model membranes to suitably mimic the
      biological cell membrane for biophysical and biochemical studies by a variety of
      techniques including NMR and X-ray crystallography. Recent NMR studies have
      successfully utilized bicelles for atomic-resolution structural and dynamic
      studies of antimicrobial peptides, amyloid peptides, and membrane-bound proteins.
      Though bicelles composed with several different types of lipids and detergents
      have been reported, the NMR requirement of magnetic alignment of bicelles limits
      the temperature range in which they can be used and subsequently their
      composition. Because of this restriction, low-temperature experiments desirable
      for heat-sensitive membrane proteins have not been conducted because bicelles
      could not be aligned. In this study, we characterize the magnetic alignment of
      bicelles with various compositions for a broad range of temperatures using (31)P
      static NMR spectroscopy in search of temperature-resistant bicelles. Our
      systematic investigation identified a temperature range of magnetic alignment for
      bicelles composed of 4:1 DLPC:DHexPC, 4:1:0.2 DLPC:DHexPC:cholesterol, 4:1:0.13
      DLPC:DHexPC:CTAB, 4:1:0.13:0.2 DLPC:DHexPC:CTAB:cholesterol, and 4:1:0.4
      DLPC:DHexPC:cholesterol-3-sulfate. The amount of cholesterol-3-sulfate used was
      based on mole percent and was varied in order to determine the optimal amount.
      Our results indicate that the presence of 75 wt % or more water is essential to
      achieve maximum magnetic alignment, while the presence of cholesterol and
      cholesterol-3-sulfate stabilizes the alignment at extreme temperatures and the
      positively charged CTAB avoids the mixing of bicelles. We believe that the use of
      magnetically aligned 4:1:0.4 DLPC:DHexPC:cholesterol-3-sulfate bicelles at as low
      as -15  degrees C would pave avenues to study the structure, dynamics, and
      membrane orientation of heat-sensitive proteins such as cytochrome P450 and could
      also be useful to investigate protein-protein interactions in a membrane
      environment. 

PMID- 24460181
TI  - Contribution of the alpha8 integrin chain to the expression of extracellular
      matrix components.
AB  - In the kidney, the alpha8 integrin chain (itga8) is expressed in mesenchymal
      cells and is upregulated in fibrotic disease. We hypothesized that itga8 mediates
      a profibrotic phenotype of renal cells by promoting extracellular matrix and
      cytokine expression. Genetic itga8 deficiency caused complex changes in matrix
      expression patterns in mesangial and smooth-muscle cells, with the only
      concordant effect in both cell types being a reduction of collagen III
      expression. Silencing of itga8 with siRNA led to a decline of matrix turnover
      with repression of matrix metalloproteinases and reduction of matrix production.
      In contrast, de novo expression of itga8 in tubular epithelial cells resulted in
      reduced collagen synthesis. Overexpression of itga8 in fibroblasts did not change
      the expression of matrix molecules or regulators of matrix turnover. Thus, the
      influence of itga8 on the expression of matrix components was not uniform and
      celltype dependent. Itga8 seems unlikely to exert overall profibrotic effects in
      renal cells.

PMID- 24460183
TI  - Label-free detection of native proteins by surface-enhanced Raman spectroscopy
      using iodide-modified nanoparticles.
AB  - Proteins perform vital functional and structural duties in living systems, and
      the in-depth investigation of protein in its native state is one of the most
      important challenges in the postgenomic era. Surface-enhanced Raman spectroscopy
      (SERS) can provide the intrinsic fingerprint information of samples with
      ultrahigh sensitivity but suffers from the reproducibility and reliability
      issues. In this paper, we proposed an iodide-modified Ag nanoparticles method (Ag
      IMNPs) for label-free detection of proteins. The silver nanoparticles provide the
      huge enhancement to boost the Raman signal of proteins, and the coated iodide
      layer offers a barrier to prevent the direct interaction between the proteins and
      the metal surface, helping to keep the native structures of proteins. With this
      method, highly reproducible and high-quality SERS signals of five typical
      proteins (lysozyme, avidin, bovine serum albumin, cytochrome c, and hemoglobin)
      have been obtained, and the SERS features of the proteins without chromophore
      were almost identical to the respective normal Raman spectra. This unique feature
      allows the qualitative identification of them by simply taking the intensity
      ratio of the Raman peaks of tryptophan to phenylalanine residues. We further
      demonstrated that the method can also be used for label-free multiplex analysis
      of protein mixture as well as to study the dynamic process of protein damage
      stimulated by hydrogen peroxide. This method proves to be very promising for
      further applications in proteomics and biomedical research. 

PMID- 24460185
TI  - Notes on continuing education.

PMID- 24460184
TI  - Thalidomide increases human hepatic cytochrome P450 3A enzymes by direct
      activation of the pregnane X receptor.
AB  - Heterotropic cooperativity of human cytochrome P450 (P450) 3A4/3A5 by the
      teratogen thalidomide was recently demonstrated by H. Yamazaki et al. ( ( 2013 )
      Chem. Res. Toxicol. 26 , 486 - 489 ) using the model substrate midazolam in
      various in vitro and in vivo models. Chimeric mice with humanized liver also
      displayed enhanced midazolam clearance upon pretreatment with orally administered
      thalidomide, presumably because of human P450 3A induction. In the current study,
      we further investigated the regulation of human hepatic drug metabolizing
      enzymes. Thalidomide enhanced levels of P450 3A4 and 2B6 mRNA, protein
      expression, and/or oxidation activity in human hepatocytes, indirectly suggesting
      the activation of upstream transcription factors involved in detoxication, e.g.,
      the nuclear receptors pregnane X receptor (PXR) and constitutive androstane
      receptor (CAR). A key event after ligand binding is an alteration of nuclear
      receptor conformation and recruitment of coregulator proteins that alter
      chromatin accessibility of target genes. To investigate direct engagement and
      functional alteration of PXR and CAR by thalidomide, we utilized a peptide
      microarray with 154 coregulator-derived nuclear receptor-interaction motifs and
      coregulator and nuclear receptor boxes, which serves as a sensor for nuclear
      receptor conformation and activity status as a function of ligand. Thalidomide
      and its human proximate metabolite 5-hydroxythalidomide displayed significant
      modulation of coregulator interaction with PXR and CAR ligand-binding domains,
      similar to established agonists for these receptors. These results collectively
      suggest that thalidomide acts as a ligand for PXR and CAR and causes enzyme
      induction leading to increased P450 enzyme activity. The possibilities of drug
      interactions during thalidomide therapy in humans require further evaluation. 

PMID- 24460186
TI  - Electronic structure investigation and parametrization of biologically relevant
      iron-sulfur clusters.
AB  - The application of classical molecular dynamics simulations to the study of
      metalloenzymes has been hampered by the lack of suitable molecular mechanics
      force field parameters to treat the metal centers within standard biomolecular
      simulation packages. These parameters cannot be generalized, nor be easily
      automated, and hence should be obtained for each system separately. Here we
      present density functional theory calculations on [Fe2S2(SCH3)4]2+/+,
      [Fe3S4(SCH3)3]+/0 and [Fe4S4(SCH3)4]2+/+ and the derivation of parameters that
      are compatible with the AMBER force field. Molecular dynamics simulations
      performed using these parameters on respiratory Complex II of the electron
      transport chain showed that the reduced clusters are more stabilized by the
      protein environment, which leads to smaller changes in bond lengths and angles
      upon reduction. This effect is larger in the smaller iron-sulfur cluster,
      [Fe2S2(SCH3)4]2+/+.

PMID- 24460187
TI  - Tuning the Fano resonance with an intruder continuum.
AB  - Through a combination of experiment and theory we establish the possibility of
      achieving strong tuning of Fano resonances (FRs), by allowing their usual two
      path geometry to interfere with an additional, "intruder", continuum. As the
      coupling strength to this intruder is varied, we predict strong modulations of
      the resonance line shape that, in principle at least, may exceed the amplitude of
      the original FR itself. For a proof-of-concept demonstration of this phenomenon,
      we construct a nanoscale interferometer from nonlocally coupled quantum point
      contacts and utilize the unique features of their density of states to realize
      the intruder. External control of the intruder coupling is enabled by means of an
      applied magnetic field, in the presence of which we demonstrate the predicted
      distortions of the FR. This general scheme for resonant control should be broadly
      applicable to a variety of wave-based systems, opening up the possibility of new
      applications in areas such as chemical and biological sensing and secure
      communications. 

PMID- 24460188
TI  - Comparative proteomics reveals that a saxitoxin-producing and a nontoxic strain
      of Anabaena circinalis are two different ecotypes.
AB  - In Australia, saxitoxin production is restricted to the cyanobacterial species
      Anabaena circinalis and is strain-dependent. We aimed to characterize a saxitoxin
      producing and nontoxic strain of A. circinalis at the proteomic level using
      iTRAQ. Seven proteins putatively involved in saxitoxin biosynthesis were
      identified within our iTRAQ experiment for the first time. The proteomic profile
      of the toxic A. circinalis was significantly different from the nontoxic strain,
      indicating that each is likely to inhabit a unique ecological niche. Under
      control growth conditions, the saxitoxin-producing A. circinalis displayed a
      higher abundance of photosynthetic, carbon fixation and nitrogen metabolic
      proteins. Differential abundance of these proteins suggests a higher
      intracellular C:N ratio and a higher concentration of intracellular 2
      oxoglutarate in our toxic strain compared with the nontoxic strain. This may be a
      novel site for posttranslational regulation because saxitoxin biosynthesis
      putatively requires a 2-oxoglutarate-dependent dioxygenase. The nontoxic A.
      circinalis was more abundant in proteins, indicating cellular stress. Overall,
      our study has provided the first insight into fundamental differences between a
      toxic and nontoxic strain of A. circinalis, indicating that they are distinct
      ecotypes. 

PMID- 24460189
TI  - Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics.
AB  - Recent advances in our understanding of genetic-epigenetic interactions have
      unraveled new mechanisms underlying the etiology of complex autoimmune diseases.
      Autoimmune thyroid diseases (AITDs) are highly prevalent, affecting 1% to 5% of
      the population. The major AITDs include Graves disease (GD) and Hashimoto's
      thyroiditis (HT); although these diseases contrast clinically, their pathogenesis
      involves shared immunogenetic mechanisms. Genetic data point to the involvement
      of both shared and unique genes. Among the shared susceptibility genes, HLA
      DRbeta1-Arg74 (human leukocyte antigen DR containing an arginine at position
      beta74) confers the strongest risk. Recent genome-wide analyses have revealed new
      putative candidate genes. Epigenetic modulation is emerging as a major mechanism
      by which environmental factors interact with AITD susceptibility genes.
      Dissecting the genetic-epigenetic interactions underlying the pathogenesis of
      AITD is essential to uncover new therapeutic targets. 

PMID- 24460191
TI  - Diverse effects of LPA receptors on cell motile activities of cancer cells.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid that interacts with G protein
      coupled transmembrane LPA receptors (LPA1 to LPA6). LPA mediates a variety of
      cellular responses in normal cells, including cell growth, motility,
      differentiation, morphogenesis, and prevention from apoptosis. Furthermore, LPA
      signaling via LPA receptors is involved in the pathogenesis of several diseases,
      including cancer. Cell motility is one of the important properties during the
      progression of cancer cells. In recent studies, it has been demonstrated that LPA
      receptors have the diverse effects in the cell motile activities of cancer cells,
      depending on the cell types involved. In this review, we provide the current
      knowledge for the biological roles of LPA receptors in the cell motile activities
      of cancer cells.

PMID- 24460192
TI  - Effects of bisphenol A and 4-nonylphenol on cellular responses through the
      different induction of LPA receptors in liver epithelial WB-F344 cells.
AB  - Lysophosphatidic acid (LPA) signaling via G protein-coupled transmembrane LPA
      receptors (LPA1 to LPA6) mediates a variety of cellular functions, including cell
      proliferation, migration, morphogenesis, and differentiation. Recently, we
      demonstrated that the different induction of LPA receptors by estrogens regulates
      cell motile activity of rat liver epithelial WB-F344 cells. In the present study,
      to assess whether endocrine disruptors (EDs) are involved in cellular functions
      through LPA signaling, we measured cell motile activity and LPA receptor
      expressions in WB-F344 cells treated with bisphenol A (BPA) and 4-nonylphenol (4
      NP). Using quantitative real time RT-PCR analysis, the Lpar1 expression was
      elevated in BPA-treated cells, whereas the Lpar3 expression was decreased. In
      contrast, 4-NP increased the Lpar3 expression, but not the Lpar1 and Lpar2. For
      cell motility assay with a Cell Culture Insert, cell motile activity of BPA
      treated cells was significantly lower than that of untreated cells. In contrast,
      4-NP markedly enhanced cell motile activity. The effects of BPA and 4-NP on cell
      motility were inhibited by the Lpar1 or Lpar3 knockdown. These results suggest
      that BPA and 4-NP may regulate cell motile activity through the different
      induction of LPA receptors in WB-F344 cells.

PMID- 24460190
TI  - The molecular pathology of melanoma: an integrated taxonomy of melanocytic
      neoplasia.
AB  - Melanomas comprise multiple biologically distinct categories, which differ in
      cell of origin, age of onset, clinical and histologic presentation, pattern of
      metastasis, ethnic distribution, causative role of UV radiation, predisposing
      germ-line alterations, mutational processes, and patterns of somatic mutations.
      Neoplasms are initiated by gain-of-function mutations in one of several primary
      oncogenes, which typically lead to benign melanocytic nevi with characteristic
      histologic features. The progression of nevi is restrained by multiple tumor
      suppressive mechanisms. Secondary genetic alterations override these barriers and
      promote intermediate or overtly malignant tumors along distinct progression
      trajectories. The current knowledge about the pathogenesis and clinical,
      histologic, and genetic features of primary melanocytic neoplasms is reviewed and
      integrated into a taxonomic framework. 

PMID- 24460193
TI  - Editorial: the fall of mechanogrowth factor?

PMID- 24460196
TI  - Highlights from special issue: junctional targets of skin and heart diseases.
AB  - In this issue, guest editors Kathy Green and Mario Delmar, who are leaders in the
      fields of epidermal desmosomes and heart intercalated discs respectively, have
      joined forces to collate a two-part series of reviews focused on junctional
      proteins and genes that are targets of skin and heart diseases.

PMID- 24460197
TI  - When rare illuminates common: how cardiocutaneous syndromes transformed our
      perspective on arrhythmogenic cardiomyopathy.
AB  - The classic cardiocutaneous syndromes of Naxos and Carvajal are rare. The
      myocardial disorder integral to their pathology - arrhythmogenic cardiomyopathy -
      is arguably not uncommon, with a prevalence of up to 1 in 1,000 despite almost
      certain under-recognition. Yet the study of cardiocutaneous syndromes has been
      integral to evolution of the contemporary perspective of arrhythmogenic
      cardiomyopathy - its clinical course, disease spectrum, genetics, and cellular
      and molecular mechanisms. Here we discuss how recognition of the association of
      hair and skin abnormalities with underlying heart disease transformed our
      conception of a little-understood but important cause of sudden cardiac death.

PMID- 24460199
TI  - Plakophilins in desmosomal adhesion and signaling.
AB  - The regulation of adhesion and growth is important for epithelial function and
      dysfunction. beta-catenin (armadillo in Drosophila) is the prototype of a
      multifunctional molecule that regulates cell adhesion via adherens junctions and
      cell signaling via LEF/TCF transcription factors. Desmosomal armadillo proteins
      comprise plakoglobin and the plakophilins 1, 2, and 3. These proteins are
      essential for building up the desmosome and linking the desmosomal cadherins to
      keratin filaments. High expression of plakophilins in desmosomes correlates with
      strong intercellular cohesion and is essential for tissue integrity under
      mechanical stress. However, like beta-catenin, these proteins have diverse non
      desmosomal functions, for example, in regulating actin organization, protein
      synthesis, and growth control. In line with these functions, their de-regulated
      expression with up- as well as down-regulation has been connected to cancer and
      metastasis. Now, recent evidence sheds light on the post-translational regulation
      and provides an explanation for how de-regulation of plakophilins can contribute
      to cancer.

PMID- 24460198
TI  - Remodeling of cell-cell junctions in arrhythmogenic cardiomyopathy.
AB  - Arrhythmogenic cardiomyopathy (AC) is a primary myocardial disorder characterized
      by a high incidence of ventricular arrhythmias often preceding the onset of
      ventricular remodeling and dysfunction. Approximately 50% of patients diagnosed
      with AC have one or more mutations in genes encoding desmosomal proteins,
      although non-desmosomal genes have also been associated with the disease.
      Increasing evidence implicates remodeling of intercalated disk proteins
      reflecting abnormal responses to mechanical load and aberrant cell signaling
      pathways in the pathogenesis of AC. This review summarizes recent advances in
      understanding disease mechanisms in AC that have come from studies of human
      myocardium and experimental models.

PMID- 24460202
TI  - Desmosomal adhesion in vivo.
AB  - Desmosomes are intercellular junctions that provide strong adhesion or hyper
      adhesion in tissues. Here, we discuss the molecular and structural basis of this
      with particular reference to the desmosomal cadherins (DCs), their isoforms and
      evolution. We also assess the role of DCs as regulators of epithelial
      differentiation. New data on the role of desmosomes in development and human
      disease, especially wound healing and pemphigus, are briefly discussed, and the
      importance of regulation of the adhesiveness of desmosomes in tissue dynamics is
      considered.

PMID- 24460203
TI  - Desmosomal cadherins and signaling: lessons from autoimmune disease.
AB  - Autoantibodies from patients suffering from the autoimmune blistering skin
      disease pemphigus can be applied as tools to study desmosomal adhesion. These
      autoantibodies targeting the desmosomal cadherins desmoglein (Dsg) 1 and Dsg3
      cause disruption of desmosomes and loss of intercellular cohesion. Although
      pemphigus autoantibodies were initially proposed to sterically hinder desmosomes,
      many groups have shown that they activate signaling pathways which cause
      disruption of desmosomes and loss of intercellular cohesion by uncoupling the
      desmosomal plaque from the intermediate filament cytoskeleton and/or by
      interfering with desmosome turnover. These studies demonstrate that desmogleins
      serve as receptor molecules to transmit outside-in signaling and demonstrate that
      desmosomal cadherins have functions in addition to their adhesive properties. Two
      central molecules regulating cytoskeletal anchorage and desmosome turnover are
      p38MAPK and PKC. As cytoskeletal uncoupling in turn enhances Dsg3 depletion from
      desmosomes, both mechanisms reinforce one another in a vicious cycle that
      compromise the integrity and number of desmosomes.

PMID- 24460201
TI  - Integrating animal models and in vitro tissue models to elucidate the role of
      desmosomal proteins in diseases.
AB  - Desmosomes are intercellular junctions that provide tissues with structural
      stability. These junctions might also act as signaling centers that transmit
      environmental clues to the cell, thereby affecting cell differentiation,
      migration, and proliferation. The importance of desmosomes is underscored by
      devastating skin and heart diseases caused by mutations in desmosomal genes.
      Recent observations suggest that abnormal desmosomal protein expression might
      indirectly contribute to skin disorders previously not linked to these proteins.
      For example, it has been postulated that reduced desmosomal protein expression
      occurs in patients affected by Ankyloblepharon-ectodermal defects-cleft
      lip/palate syndrome (AEC), a skin fragility disorder caused by mutations in the
      transcription factor TP63. Currently, it is not clear how these changes in
      desmosomal gene expression contribute to AEC. We will discuss new approaches that
      combine in vitro and in vivo models to elucidate the role of desmosomal gene
      deregulation in human skin diseases such as AEC.

PMID- 24460200
TI  - Trafficking highways to the intercalated disc: new insights unlocking the
      specificity of connexin 43 localization.
AB  - With each heartbeat, billions of cardiomyocytes work in concert to propagate the
      electrical excitation needed to effectively circulate blood. Regulated expression
      and timely delivery of connexin proteins to form gap junctions at the specialized
      cell-cell contact region, known as the intercalated disc, is essential to
      ventricular cardiomyocyte coupling. We focus this review on several regulatory
      mechanisms that have been recently found to govern the lifecycle of connexin 43
      (Cx43), the short-lived and most abundantly expressed connexin in cardiac
      ventricular muscle. The Cx43 lifecycle begins with gene expression, followed by
      oligomerization into hexameric channels, and then cytoskeletal-based transport
      toward the disc region. Once delivered, hemichannels interact with resident disc
      proteins and are organized to effect intercellular coupling. We highlight recent
      studies exploring regulation of Cx43 localization to the intercalated disc, with
      emphasis on alternatively translated Cx43 isoforms and cytoskeletal transport
      machinery that together regulate Cx43 gap junction coupling between
      cardiomyocytes.

PMID- 24460208
TI  - Asymmetric and symmetric bolaform supra-amphiphiles: formation of imine bond
      influenced by aggregation.
AB  - A series of bolaform supra-amphilphiles with different symmetries were fabricated
      through dynamic benzoic imine bond formation. The pH dependence of imine
      formations of these supra-amphiphiles were characterazied. We found that the
      extent of the imine formation of these supra-amphiphies were different. The supra
      amphiphiles with a poorer symmetry always exhibited a lower imine formation at a
      given pH. Therefore, the varied extent of imine bond formation indicate the
      different aggregations of these supra-amphilphiles, which are controlled by the
      molecular symmetry of the supra-amphiphiles. 

PMID- 24460204
TI  - Binding-induced fluorescence of serotonin transporter ligands: A spectroscopic
      and structural study of 4-(4-(dimethylamino)phenyl)-1-methylpyridinium (APP(+))
      and APP(+) analogues.
AB  - The binding-induced fluorescence of 4-(4-(dimethylamino)-phenyl)-1
      methylpyridinium (APP(+)) and two new serotonin transporter (SERT)-binding
      fluorescent analogues, 1-butyl-4-[4-(1-dimethylamino)phenyl]-pyridinium bromide
      (BPP(+)) and 1-methyl-4-[4-(1-piperidinyl)phenyl]-pyridinium (PPP(+)), has been
      investigated. Optical spectroscopy reveals that these probes are highly sensitive
      to their chemical microenvironment, responding to variations in polarity with
      changes in transition energies and responding to changes in viscosity or
      rotational freedom with emission enhancements. Molecular docking calculations
      reveal that the probes are able to access the nonpolar and conformationally
      restrictive binding pocket of SERT. As a result, the probes exhibit previously
      not identified binding-induced turn-on emission that is spectroscopically
      distinct from dyes that have accumulated intracellularly. Thus, binding and
      transport dynamics of SERT ligands can be resolved both spatially and
      spectroscopically.

PMID- 24460209
TI  - Microscopic methods to observe the distribution of lipids in the cellular
      membrane.
AB  - Membrane lipids not only provide the structural framework of cellular membranes
      but also influence protein functions in several different ways. In comparison to
      proteins, however, relatively little is known about distribution of membrane
      lipids because of the insufficiency of microscopic methods. The difficulty in
      studying lipid distribution results from several factors, including their
      unresponsiveness to chemical fixation, fast translational movement, small
      molecular size, and high packing density. In this Current Topic, we consider the
      major microscopic methods and discuss whether and to what degree of precision
      these methods can reveal membrane lipid distribution in situ. We highlight two
      fixation methods, chemical and physical, and compare the theoretical limitations
      to their spatial resolution. Recognizing the strengths and weaknesses of each
      method should help researchers interpret their microscopic results and increase
      our understanding of the physiological functions of lipids. 

PMID- 24460212
TI  - Bioactivation of cinnamic alcohol forms several strong skin sensitizers.
AB  - Cinnamic alcohol is a frequent contact allergen, causing allergic contact
      dermatitis (ACD) in a substantial number of individuals sensitized from contacts
      with fragrances. Hence, cinnamic alcohol is one of the constituents in fragrance
      mix I (FM I) used for screening contact allergy in dermatitis patients. Cinnamic
      alcohol lacks structural alerts for protein reactivity and must therefore be
      activated by either air oxidation or bioactivation to be able to act as a
      sensitizer. In the present study, we explored the bioactivation of cinnamic
      alcohol using human liver microsomes (HLM), and the potential pathways for these
      reactions were modeled by in silico (DFT) techniques. Subsequently, the
      reactivity of cinnamic alcohol and its metabolites toward a model hexapeptide
      were investigated. In addition to cinnamic aldehyde and cinnamic acid, two highly
      sensitizing epoxides previously unobserved in studies of bioactivation were
      detected in the incubations with HLMs. Formation of epoxy cinnamic aldehyde was
      shown (both by the liver microsomal experiments, in which no depletion of epoxy
      cinnamic alcohol was observed after initial formation, and by the very high
      activation energy found for the oxidation thereof by calculations) to proceed via
      cinnamic aldehyde and not epoxy cinnamic alcohol.

PMID- 24460213
TI  - Computational fluid dynamics simulation to evaluate aortic coarctation gradient
      with contrast-enhanced CT.
AB  - Coarctation of aorta (CoA) is a narrowing of the aorta leading to a pressure
      gradient (DeltaP) across the coarctation, increased afterload and reduced
      peripheral perfusion pressures. Indication to invasive treatment is based on
      values of maximal (systolic) trans-coarctation DeltaP. A computational fluid
      dynamic (CFD) approach is herein presented for the non-invasive haemodynamic
      assessment of DeltaP across CoA. Patient-specific CFD simulations were created
      from contrast-enhanced computed tomography (CT) and appropriate flow boundary
      conditions. Computed DeltaP was validated with invasive intravascular trans-CoA
      pressure measurements. Haemodynamic indices, including pressure loss coefficient
      (PLc), time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI),
      were also quantified. CFD-estimated DeltaP values were comparable to the invasive
      ones. Moreover, the aorta proximal to CoA was exposed to altered TAWSS and OSI
      suggesting hypertension. PLc was found as a further geometric marker of CoA
      severity. Finally, CFD-estimated DeltaP confirmed a significant reduction after
      percutaneous balloon dilatation and stenting of the CoA in one patient (e.g. from
      DeltaP~52 mmHg to DeltaP~3 mmHg). The validation of the DeltaP computations with
      catheterisation measurements suggests that CFD simulation, based on CT-derived
      anatomical data, is a useful tool to readily quantify CoA severity.

PMID- 24460210
TI  - Pathway analysis for drug repositioning based on public database mining.
AB  - Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of
      action (MOAs) and clinical functions by pathway analysis based on retrieved drug
      targets interacting with or affected by the investigated drugs. Protein and gene
      targets and associated pathways were obtained by data-mining of public databases
      including the MMDB, PubChem BioAssay, GEO DataSets, and the BioSystems databases.
      Entrez E-Utilities were applied, and in-house Ruby scripts were developed for
      data retrieval and pathway analysis to identify and evaluate relevant pathways
      common to the retrieved drug targets. Pathways pertinent to clinical uses or MOAs
      were obtained for most drugs. Interestingly, some drugs identified pathways
      responsible for other diseases than their current therapeutic uses, and these
      pathways were verified retrospectively by in vitro tests, in vivo tests, or
      clinical trials. The pathway enrichment analysis based on drug target information
      from public databases could provide a novel approach for elucidating drug MOAs
      and repositioning, therefore benefiting the discovery of new therapeutic
      treatments for diseases. 

PMID- 24460214
TI  - Tempo-spatially resolved scattering correlation spectroscopy under dark-field
      illumination and its application to investigate dynamic behaviors of gold
      nanoparticles in live cells.
AB  - In this study, a new tempo-spatially resolved fluctuation spectroscopy under dark
      field illumination is described, named dark-field illumination-based scattering
      correlation spectroscopy (DFSCS). DFSCS is a single-particle method, whose
      principle is similar to that of fluorescence correlation spectroscopy (FCS).
      DFSCS correlates the fluctuations of the scattered light from single nanoparticle
      under dark-field illumination. We developed a theoretical model for translational
      diffusion of nanoparticles in DFSCS system. The results of computer simulations
      documented that this model was able to well describe the diffusion behaviors of
      nanoparticles in uniformly illuminated field. The experimental setup of DFSCS was
      achieved by introducing a dark-field condenser to the frequently used bright
      field microscope and an electron multiplying charge-coupled device (EMCCD) as the
      array detector. In the optimal condition, a stack of 500 000 frames were
      collected simultaneously on 64 detection channels for a single measurement with
      acquisition rate of 0.5 ms per frame. We systematically investigated the effect
      of certain factors such as particle concentration, viscosity of the solution, and
      heterogeneity of gold nanoparticles (GNPs) samples on DFSCS measurements. The
      experiment data confirmed theoretical model proposed. Furthermore, this new
      method was successfully used for investigating dynamic behaviors of GNPs in live
      cells. Our preliminary results demonstrate that DFSCS is a practical and
      affordable tool for ordinary laboratories to investigate the dynamic information
      of nanoparticles in vitro as well as in vivo. 

PMID- 24460215
TI  - The scope of continuing nursing education as a field of practice.

PMID- 24460216
TI  - Asymmetric synthesis of (-)-aurantioclavine via palladium-catalyzed
      intramolecular allylic amination.
AB  - The total synthesis of (-)-aurantioclavine (1) was accomplished based on an
      intramolecular asymmetric amination of allyl carbonate 3 containing a p
      tosylamide group. The reaction using tris(dibenzylideneacetone)dipalladium(0),
      tBu-phosphinooxazoline, and Bu4NCl in CH2Cl2 gave azepane 2 in 77% yield with 95%
      enantiomeric excess. The obtained azepane 2 was also converted to a substructure
      of communesin F. 

PMID- 24460218
TI  - Metabolically healthy obesity and its associates in Mongolian Chinese adults.
AB  - BACKGROUND: Not all obese individuals show cardiometabolic abnormalities. We
      examined metabolically healthy obesity (MHO) and its associates in 2530 Mongolian
      Chinese adults. METHODS: MHO was defined by waist circumference, low-density
      lipoprotein (LDL-C) cholesterol, high-density lipoprotein cholesterol (HDL-C),
      triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure
      (DBP), and glucose. RESULTS: Only 3.0% of the participants had MHO, with 0.8% of
      men and 4.5% of women having this condition (P < 0.001 for sex difference).
      Despite striking differences in obesity measures, MHO individuals had a
      comparable cardiometabolic profile to that for metabolically healthy, nonobese
      individuals (MHNO) and an improved cardiometabolic profile, i.e., lower levels of
      blood pressure, glucose, insulin, LDL-C, TGs, and higher levels of HDL-C compared
      to metabolically abnormal individuals (all P < 0.01, except for insulin). MHO
      individuals had lower levels of high-sensitivity C-reactive protein and soluble
      intercellular adhesion molecule-1, compared to metabolically abnormal
      individuals, and had comparable levels of these markers to those in MHNO
      individuals. Furthermore, only 5.3% of MHO individuals had a family history of
      hypertension, comparable to 5.0% in MHNO individuals, and much lower than 15.9%
      in metabolically abnormal, nonobese individuals and 12.8% in metabolically
      abnormal, obese individuals (overall P < 0.001). CONCLUSIONS: We conclude that
      MHO is associated with a low inflammation state, and family history of
      hypertension may play a role in the MHO phenotype.

PMID- 24460219
TI  - Quantitative proteomics reveals the role of protein phosphorylation in rice
      embryos during early stages of germination.
AB  - Seed germination begins with water uptake and ends with radicle emergence. A gel
      free phosphoproteomic technique was used to investigate the role of protein
      phosphorylation events in the early stages of rice seed germination. Both seed
      weight and ATP content increased gradually during the first 24 h following
      imbibition. Proteomic analysis indicated that carbohydrate metabolism- and
      protein synthesis/degradation-related proteins were predominantly increased and
      displayed temporal patterns of expression. Analyses of cluster and protein
      protein interactions indicated that the regulation of sucrose synthases and alpha
      amylases was the central event controlling germination. Phosphoproteomic analysis
      identified several proteins involved in protein modification and transcriptional
      regulation that exhibited significantly temporal changes in phosphorylation
      levels during germination. Cluster analysis indicated that 12 protein
      modification-related proteins had a peak abundance of phosphoproteins at 12 h
      after imbibition. These results suggest that the first 12 h following imbibition
      is a potentially important signal transduction phase for the initiation of rice
      seed germination. Three core components involved in brassinosteroid signal
      transduction displayed significant increases in phosphoprotein abundance during
      the early stages of germination. Brassinolide treatment increased the rice seed
      germination rate but not the rate of embryonic axis elongation. These findings
      suggest that brassinosteroid signal transduction likely triggers seed
      germination. 

PMID- 24460221
TI  - Unsaturated fatty acids, desaturases, and human health.
AB  - With the increasing concern for health and nutrition, dietary fat has attracted
      considerable attention. The composition of fatty acids in a diet is important
      since they are associated with major diseases, such as cancers, diabetes, and
      cardiovascular disease. The biosynthesis of unsaturated fatty acids (UFA)
      requires the expression of dietary fat-associated genes, such as SCD, FADS1,
      FADS2, and FADS3, which encode a variety of desaturases, to catalyze the addition
      of a double bond in a fatty acid chain. Recent studies using new molecular
      techniques and genomics, as well as clinical trials have shown that these genes
      and UFA are closely related to physiological conditions and chronic diseases; it
      was found that the existence of alternative transcripts of the desaturase genes
      and desaturase isoforms might affect human health and lipid metabolism in
      different ways. In this review, we provide an overview of UFA and desaturases
      associated with human health and nutrition. Moreover, recent findings of UFA,
      desaturases, and their associated genes in human systems are discussed.
      Consequently, this review may help elucidate the complicated physiology of UFA in
      human health and diseases.

PMID- 24460222
TI  - Asymmetric domino multicatalysis for the synthesis of 3-substituted phthalides:
      cinchonine/NHC cooperative system.
AB  - It is demonstrated that two organocatalysts, achiral NHC and chiral bifunctional
      cinchonine, are mutually compatible and operating concurrently and effectively to
      promote the asymmetric domino oxidation/oxa-Michael addition reaction. This
      protocol allowed access to both enantiomers of a product by using two natural,
      inexpensive pseudoenantiomeric cinchona alkaloids, cinchonine and cinchonidine,
      as well as to phthalides containing a chiral quaternary carbon center in good
      enantioselectivities. 

PMID- 24460223
TI  - A web-based examination of experiences with intrusive thoughts across the adult
      lifespan.
AB  - OBJECTIVES: Intrusive thoughts and images are common across the adult lifespan,
      but vary in their consequences. Understanding age-related experiences with
      intrusive thoughts is important for identifying risk and protective factors for
      intrusive thought problems across the adult lifespan. This study characterized
      age trajectories for six aspects of experiences with intrusive thoughts using
      Internet data collection. METHOD: Participants (N = 1427; ages 18-87) were
      randomly assigned to suppress (i.e. keep out of mind) or monitor an intrusive
      thought for one minute, and then later to monitor the thought for a second
      minute. Participants tracked thought recurrences during each thinking period,
      then reported their positive and negative affects following each thinking period,
      as well as their effort expended in suppressing the thought and perceived
      difficulty controlling the intrusive thought. Multilevel modeling and generalized
      estimating equations modeled the continuous relationships between age and each
      dependent variable. RESULTS: As expected, older age was associated with less
      decline in positive affect while engaging with an intrusive thought.
      Interestingly, older age was also associated with a sharper rise and fall of
      negative affect. Suppression effort increased linearly with age (though perceived
      difficulty did not). Finally, no age differences were found in either the
      frequency or duration of the thought's recurrence, adding to previous evidence
      that older adults function similarly to younger adults in their control of
      intrusive thoughts, despite certain age-related declines in cognitive
      functioning. CONCLUSION: These findings suggest a dissociation between age
      related changes in emotional versus cognitive characteristics of engaging with
      intrusive thoughts.

PMID- 24460236
TI  - Respiratory impairment in four patients associated with exposure to palytoxin
      containing coral.

PMID- 24460237
TI  - Thirty U.S. Poison Center reports later: greater demand, more difficult problems.

PMID- 24460238
TI  - Patellar tendon and hamstring moment-arms and cross-sectional area in patients
      with anterior cruciate ligament reconstruction and controls.
AB  - The purpose of this study was to examine the moment-arm and cross-sectional area
      (CSA) of the patellar tendon (PT) and the hamstrings after anterior cruciate
      ligament (ACL) reconstruction. The right knee of five males who underwent ACL
      reconstruction with a PT graft and five age-matched controls was scanned using
      magnetic resonance image scans. Based on three-dimensional (3D) solids of the PT,
      CSAs and moment-arms of semitendinous (ST), biceps femoris (BF) long head and
      semimembranosus (SM) were estimated. Analysis of variance indicated no
      significant group differences in muscle moment-arms (p>0.05). 3D moment-arms of
      PT, ST and BF were significantly lower than the corresponding 2D values (p <
      0.05). The ACL group displayed a significantly higher maximum BF CSA, a lower ST
      CSA (p < 0.05) but similar PT and SM CSAs compared with controls. It is concluded
      that any alterations in PT properties 1 year after harvesting do not affect knee
      muscle moment-arms compared with age-matched controls. Moment-arm estimation
      differed between 3D and 2D data, although it did not affect comparisons between
      ACL reconstruction group and controls. Design of rehabilitation programmes should
      take into consideration a potential alteration in hamstring morphology following
      surgery with a PT graft.

PMID- 24460239
TI  - Rheology and adhesion of poly(acrylic acid)/laponite nanocomposite hydrogels as
      biocompatible adhesives.
AB  - Biocompatible nanocomposite hydrogels (NC gels) consisting of poly(acrylic acid)
      (PAA) and nanosized clay (Laponite) were successfully synthesized by in situ free
      radical polymerization of acrylic acid (AA) in aqueous solutions of Laponite. The
      obtained NC gels were uniform and transparent. Their viscosity, storage modulus
      G', and loss modulus G" increased significantly upon increasing the content of
      Laponite and the dose of AA, while exhibiting a maximum with increasing the
      neutralization degree of AA. They showed tunable adhesion by changing the dose of
      Laponite and monomer as well as the neutralization degree of AA, as determined by
      180 degrees  peel strength measurement. The maximal adhesion was shown when
      reaching a balance between cohesion and fluidity. A homemade Johnson-Kendall
      Roberts (JKR) instrument was employed to study the surface adhesion behavior of
      the NC gels. The combination of peel strength, rheology, and JKR measurements
      offers the opportunity of insight into the mechanism of adhesion of hydrogels.
      The NC gels with tunable adhesion should be ideal candidates for dental adhesive,
      wound dressing, and tissue engineering. 

PMID- 24460240
TI  - Identifying proteins in zebrafish embryos using spectral libraries generated from
      dissected adult organs and tissues.
AB  - Spectral libraries provide a sensitive and accurate method for identifying
      peptides from tandem mass spectra, complementary to searching genome-derived
      databases or sequencing de novo. Their application requires comprehensive
      libraries including peptides from low-abundant proteins. Here we describe a
      method for constructing such libraries using biological differentiation to
      "fractionate" the proteome by harvesting adult organs and tissues and build
      comprehensive libraries for identifying proteins in zebrafish (Danio rerio)
      embryos and larvae (an important and widely used model system). Hierarchical
      clustering using direct comparison of spectra was used to prioritize organ
      selection. The resulting and publicly available library covers 14,164 proteins,
      significantly improved the number of peptide-spectrum matches in zebrafish
      developmental stages, and can be used on data from different instruments and
      laboratories. The library contains information on tissue and organ expression of
      these proteins and is also applicable for adult experiments. The approach itself
      is not limited to zebrafish but would work for any model system.

PMID- 24460242
TI  - Choosing feature selection and learning algorithms in QSAR.
AB  - Feature selection is an important part of contemporary QSAR analysis. In a
      recently published paper, we investigated the performance of different feature
      selection methods in a large number of in silico experiments conducted using real
      QSAR datasets. However, an interesting question that we did not address is
      whether certain feature selection methods are better than others in combination
      with certain learning methods, in terms of producing models with high prediction
      accuracy. In this report we extend our work from the previous investigation by
      using four different feature selection methods (wrapper, ReliefF, MARS, and
      elastic nets), together with eight learners (MARS, elastic net, random forest,
      SVM, neural networks, multiple linear regression, PLS, kNN) in an empirical
      investigation to address this question. The results indicate that state-of-the
      art learners (random forest, SVM, and neural networks) do not gain prediction
      accuracy from feature selection, and we found no evidence that a certain feature
      selection is particularly well-suited for use in combination with a certain
      learner. 

PMID- 24460244
TI  - Multifunctional two-photon active silica-coated Au@MnO Janus particles for
      selective dual functionalization and imaging.
AB  - Monodisperse multifunctional and nontoxic Au@MnO Janus particles with different
      sizes and morphologies were prepared by a seed-mediated nucleation and growth
      technique with precise control over domain sizes, surface functionalization, and
      dye labeling. The metal oxide domain could be coated selectively with a thin
      silica layer, leaving the metal domain untouched. In particular, size and
      morphology of the individual (metal and metal oxide) domains could be controlled
      by adjustment of the synthetic parameters. The SiO2 coating of the oxide domain
      allows biomolecule conjugation (e.g., antibodies, proteins) in a single step for
      converting the photoluminescent and superparamagnetic Janus nanoparticles into
      multifunctional efficient vehicles for theranostics. The Au@MnO@SiO2 Janus
      particles were characterized using high-resolution transmission electron
      microscopy (HR-)TEM, powder X-ray diffraction (PXRD), optical (UV-vis)
      spectroscopy, confocal laser fluorescence scanning microscopy (CLSM), and dynamic
      light scattering (DLS). The functionalized nanoparticles were stable in buffer
      solution or serum, showing no indication of aggregation. Biocompatibility and
      potential biomedical applications of the Au@MnO@SiO2 Janus particles were assayed
      by a cell viability analysis by coincubating the Au@MnO@SiO2 Janus particles with
      Caki 1 and HeLa cells. Time-resolved fluorescence spectroscopy in combination
      with CLSM revealed the silica-coated Au@MnO@SiO2 Janus particles to be highly two
      photon active; no indication for an electronic interaction between the dye
      molecules incorporated in the silica shell surrounding the MnO domains and the
      attached Au domains was found; fluorescence quenching was observed when dye
      molecules were bound directly to the Au domains. 

PMID- 24460246
TI  - Eicosapentaenoic acid and docosahexaenoic acid suppress Th2 cytokine expression
      in RBL-2H3 basophilic leukemia cells.
AB  - It is known that the intake of omega-3 fatty acids, such as eicosapentaenoic
      (EPA) and docosahexaenoic acid (DHA), is beneficial for preventing and/or
      treating allergic diseases. The pathogenesis of allergic diseases is associated
      with overactivation of Th2-skewed immunity. Basophils generate large amounts of
      Th2 cytokines such as interleukin (IL)-4 and IL-13, which are critically involved
      in allergic inflammation. We investigated how EPA and DHA affect Th2 cytokine
      expression in phorbol 12-myristate 13-acetate- and ionomycin (PI)-activated RBL
      2H3 basophilic leukemia cells. EPA and DHA induced a dramatic decrease in the
      production of IL-4 and IL-13 and their transcription in a dose-dependent manner.
      Luciferase assays of RBL-2H3 cells stably expressing Il4 and Il13 promoter
      reporter plasmids demonstrated a significant suppression of PI-induced promoter
      activation. Analysis of certain transcription factors revealed that nuclear
      expression of c-Fos and the mRNA expression were suppressed by EPA and DHA.
      Furthermore, they significantly inhibited the nuclear expression and
      translocation of nuclear factor of activated T cells (NF-AT)1. In contrast, the
      expression levels of nuclear factor kappa-B (NF-kappaB), GATA-binding proteins
      (GATAs), and CCAAT/enhancer binding protein alpha (C/EBPalpha) were not
      significantly affected by EPA and DHA. Phosphorylation of extracellular signal
      related kinase was inhibited by EPA and DHA, and phosphorylation of p38 mitogen
      activated protein kinase was decreased by DHA, but not by EPA. Taken together,
      our data suggest that EPA and DHA may suppress Th2-skewed allergic immune
      responses by inhibiting the expression of basophilic IL-4 and IL-13.

PMID- 24460247
TI  - Selected readings.

PMID- 24460248
TI  - Effect of direct education on breast self examination awareness and practice
      among women in Bolu, Turkey.
AB  - AIMS: To evaluate breast self examination (BSE) practice and the effect of a
      training program conducted by healthcare professionals on BSE. MATERIALS AND
      METHODS: Women were randomized into control and test groups with both groups
      completing a questionnaire and three independent interviews where their BSE
      practices were evaluated. RESULTS: In all, 39.5% of the participants were
      previously provided information on BSE by healthcare professionals while 25.8%
      had no knowledge of BSE prior to enrollment. Compared to those informed about BSE
      through other means such as television, radio, and the internet, the scores of
      the first, second, and third visits were higher (p<0.05) in individuals who
      received BSE education from healthcare professionals and hospitals. CONCLUSIONS:
      BSE training provided by healthcare professionals may increase early breast
      cancer diagnosis and treatment rates by improving BSE awareness and practice.

PMID- 24460249
TI  - RNAi and miRNA in viral infections and cancers.
AB  - Since the first report of RNA interference (RNAi) less than a decade ago, this
      type of molecular intervention has been introduced to repress gene expression in
      vitro and also for in vivo studies in mammals. Understanding the mechanisms of
      action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic
      agents in the areas of cancer and viral infection. Recent studies have also
      promoted different theories about cell-specific targeting of siRNAs. Design and
      delivery strategies for successful treatment of human diseases are becomingmore
      established and relationships between miRNA and RNAi pathways have been revealed
      as virus-host cell interactions. Although both are well conserved in plants,
      invertebrates and mammals, there is also variabilityand a more complete
      understanding of differences will be needed for optimal application. RNA
      interference (RNAi) is rapid, cheap and selective in complex biological systems
      and has created new insight sin fields of cancer research, genetic disorders,
      virology and drug design. Our knowledge about the role of miRNAs and siRNAs
      pathways in virus-host cell interactions in virus infected cells is incomplete.
      There are different viral diseases but few antiviral drugs are available. For
      example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B
      viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an
      important target for siRNA-based therapies, but the main problem in cancer
      therapy is targeting metastatic cells which spread from the original tumor. There
      are also other possible reservations and problems that might delay or even hinder
      siRNA-based therapies for the treatment of certain conditions; however, this
      remains the most promising approach for a wide range of diseases. Clearly, more
      studies must be done to allow efficient delivery and better understanding of
      unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi
      biology, experimental design, anti-viral and anti-cancer effects are discussed. 

PMID- 24460250
TI  - How to establish acute myeloid leukemia xenograft models using immunodeficient
      mice.
AB  - The discovery of the immunodeficient mice has provided a tool for establishing
      animal models as hosts for in vivo analysis of AML. Various model systems have
      been established in the last few decades, and it is essential that murine AML
      models are developed to exploit more specific, targeted therapeutics. In this
      review, we concentrate on the models of AML and discuss the development of
      immunodeficiency models for understanding of leukemogenesis, describe those now
      available and their values and document the methods used for establishing and
      identifying AML mice models, as well as factors influencing engraftment of human
      AML in immunodeficient mice. Thus, the function of this article is to provide
      clinicians and experimentalists with a chronological, comprehensive appraisal of
      all AML model systems. 

PMID- 24460251
TI  - Dokha: an emerging public health issue as a form of tobacco smoking in the middle
      East.
AB  - BACKGROUND: Tobacco use is one of the leading causes of preventable death across
      the world today and the smoking rates among men in the Arab world are amongst the
      highest in the world. Smoking of dokha, a traditional Arab tobacco is common in
      some of the Middle East countries such as the United Arab Emirates and Iran. This
      review focuses on the prevalence, pattern and health effects of dokha use in the
      Middle East. For this purpose an electronic search was performed in the following
      databases and websites: MEDLINE, EMBASE, Proquest and Google scholar up to
      December 2012. The search strategy was based on Internet search for the synonyms
      of dohka or midwakh. From the results of the review it emerged that younger
      people are the most common users of dokha. Hence effective outreach health
      education programs, targeting adolescents, especially school students before they
      take up the habit of smoking, may thus curb the emergence of the problem.

PMID- 24460252
TI  - Connections between various trigger factors and the RIP1/ RIP3 signaling pathway
      involved in necroptosis.
AB  - Programmed cell death is a basic cellular process that is critical to maintaining
      tissue homeostasis. In contrast to apoptosis, necrosis was previously regarded as
      an unregulated and uncontrollable process. However, as research has progressed,
      necrosis, also known as necroptosis or programmed necrosis, is drawing increasing
      attention, not least becasu of its possible impications for cancer research.
      Necroptosis exhibits a unique signaling pathway that requires the involvement of
      receptor interaction protein kinases 1 and 3 (RIP1 and RIP3), mixed lineage
      kinase domain-like (MLKL), and phosphoglycerate mutase 5 (PGAM5) and can be
      specifically inhibited by necrostatins. Not only does necroptosis serve as a
      backup cell death program when apoptosis is inhibited, but it is now recognized
      to play a pivotal role in regulating various physiological processes and the
      pathogenesis of a variety of human diseases such as ischemic brain injury, immune
      system disorders and cancer. The control of necroptosis by various defined
      trigger factors and signaling pathways now offers the opportunity to target this
      cellular process for therapeutic purposes. The purpose of this paper is to review
      current findings concerning the connections between various trigger factors and
      the RIP1/RIP3 signaling pathway as it relates to necroptosis. 

PMID- 24460253
TI  - Correlation of habits and clinical findings with histopathological diagnosis in
      oral submucosal fibrosis patients.
AB  - BACKGROUND: Oral submucosal fibrosis (OSMF) is one of the most prevalent
      premalignant conditions in India which is easy to diagnose but difficult to
      manage. At present it is considered as irreversible and incurable. It has also
      been referred to as an epidemic in India. AIMS AND OBJECTIVES: To correlate the
      frequency and duration of habits with clinical staging, functional staging and
      histopathological grading and to correlate the clinical and functional staging
      with histopathological grading. MATERIALS AND METHODS: The study included a total
      of 90 subjects, 80 with OSMF in the experimental group and 10 patients in the
      control group. Patient personal history was recorded with chewing habits,
      including frequency and duration of chewing. The site of keeping the quid, time
      duration and whether he/she swallows it or spits it were also noted. Clinical
      staging was done on the presence of palpable fibrous bands. Functional staging
      was accomplished by measuring mouth opening. Incisional biopsy was done for all
      the patients for histopathological examination. Histopathological grading was
      according to Pindborg and Sirsat. RESULTS: The experimental group comprised 71
      males and 9 females, the majority of which were in the age group of 21-30 years.
      Correlation of habits with clinical staging, functional staging and
      histopathological grading were significant (p<0.05). Clinical and functional
      staging did not correlate with histopathological grading, but the correlation of
      clinical and functional staging was highly significant (p<0.01). CONCLUSIONS: The
      widespread habit of chewing gutkha is a major risk factor for OSMF, especially in
      the younger age group. In this study, it was found that with increase in the
      duration and frequency of the habit the severity of the disease increased.

PMID- 24460254
TI  - MicroRNA-802 promotes osteosarcoma cell proliferation by targeting p27.
AB  - MicroRNAs have been demonstrated to regulate proliferation and apoptosis in many
      types of cancers, but biological functions in osteosarcomas remain relatively
      unknown. Here, we found expression of miR-802 to be up-regulated in osteosarcoma
      tissues in comparison with adjacent normal tissues. Enforced expression of miR
      802 was able to promote cell proliferation in U2OS and MG63 cells, while miR-802
      antisense oligonucleotides (antisense miR-802) inhibited cell proliferation. At
      the molecular level, our results further revealed that expression of p27, a
      negative cell-cycle regulator, was negatively regulated by miR-802. Therefore,
      the data reported here indicate that miR-802 is an important regulator in
      osteosarcoma, our findings contributing to a better understanding of important
      mis-regulated miRNAs in this tumour type. 

PMID- 24460255
TI  - MicroRNA-155 expression has prognostic value in patients with non-small cell lung
      cancer and digestive system carcinomas.
AB  - OBJECTIVE: Published data have shown that microRNAs (miRNAs) could play a
      potential role as diagnostic and prognostic indicators in cancers. Data for the
      predictive value of microRNA-155 are inconclusive. The aim of the present
      analysis was therefore to evaluate the role of miR-155 in prognosis for patients
      with a variety of carcinomas. METHODS: Relevant studies were identified by
      searching PubMed and EMBASE. Data were extracted from studies comparing overall
      survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS)
      in patients with carcinoma with higher miR-155 expression and those with lower
      levels. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miR
      155 for clinical outcome were calculated. RESULTS: A total of 15 studies were
      included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in
      cancerous tissue was 1.89 (95% CI: 1.20-2.99, P =0.006), which could markedly
      predict poorer survival in general cancer. For RFS/CSS, elevated miR-155 was also
      associated with poor prognosis of cancer (HR= 1.50, 95% CI: 1.10-2.05, P = 0.01).
      On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC)
      was 2.09 (95% CI: 0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05
      1.55, P = 0.015), with statistical significance; the pooled HRs for OS and
      RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P =0.003) and
      2.61 (95% CI: 1.98-3.42, P<0.05), respectively. CONCLUSIONS: The results
      indicated that the miR-155 expression level plays a prognostic role in patients
      with cancer, especially NSCLCs and digestive system carcinomas.

PMID- 24460256
TI  - Genetic variation in a DNA double strand break repair gene in saudi population: a
      comparative study with worldwide ethnic groups.
AB  - DNA repair capacity is crucial in maintaining cellular functions and homeostasis.
      However, it can be altered based on DNA sequence variations in DNA repair genes
      and this may lead to the development of many diseases including malignancies.
      Identification of genetic polymorphisms responsible for reduced DNA repair
      capacity is necessary for better prevention. Homologous recombination (HR), a
      major double strand break repair pathway, plays a critical role in maintaining
      the genome stability. The present study was performed to determine the frequency
      of the HR gene XRCC3 Exon 7 (C18067T, rs861539) polymorphisms in Saudi Arabian
      population in comparison with epidemiological studies by "MEDLINE" search to
      equate with global populations. The variant allelic (T) frequency of XRCC3 (C>T)
      was found to be 39%. Our results suggest that frequency of XRCC3 (C>T) DNA repair
      gene exhibits distinctive patterns compared with the Saudi Arabian population and
      this might be attributed to ethnic variation. The present findings may help in
      high-risk screening of humans exposed to environmental carcinogens and cancer
      predisposition in different ethnic groups. 

PMID- 24460257
TI  - Selective inhibition of bicyclic tetrapeptide histone deacetylase inhibitor on
      HDAC4 and K562 leukemia cell.
AB  - Histone deacetylase (HDAC) inhibitors of cyclic peptide have been proved to be
      the most complex but the most stable and relative efficient inhibitors because of
      their large cap region. In this paper, a series of studies were carried out to
      evaluate the efficacy of synthetic bicyclic tetrapeptide inhibitors 1-5
      containing hydroxamic acid referring molecular docking, anti-proliferation,
      morphology and apoptosis. Docking analysis, together with enzyme inhibitory
      results, verified the selective capability of inhibitor 4 to HDAC4, which might
      closely related to haematological tumorigenesis, with Phe227, Asp115, Pro32,
      His198 and Ser114 participating into hydrophobic interactions and Van der Waals
      force which was familiar with former study. Moreover, inhibitor 4 inhibited K562
      cell line at the IC50 value of 1.22 MUM which was 51-67 times more efficient than
      that for U937 and HL60 cell lines. Inhibitor 4 exhibited the cell cycle-arrested
      capability to leukemia at S phase or G2/M phase as well as apoptosis-induced
      ability in different degrees. Finally, we considered that bicyclic tetrapeptide
      inhibitors were promising inhibitors used in cancer treatment and inhibitor 4
      could prevent K562 cell line well from proliferation, arrest cell cycle and
      induce K562 towards apoptosis to achieve the goals of reversing cancer cells
      which could become a potential leukemia therapeutic agent in the future. 

PMID- 24460258
TI  - Risk factors for early recurrence of HBV-related hepatocellular carcinoma meeting
      milan criteria after curative resection.
AB  - BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) after
      curative resection varies greatly. Few studies had investigated the risk factors
      for early recurrence (recurrence-free time <= 1 year) of hepatitis B virus (HBV)
      related HCCs meeting Milan criteria. METHODS: A retrospective analysis was
      performed on the 224 patients with HCC meeting Milan criteria who underwent
      curative liver resection in our center between February 2007 and March 2012. The
      overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors
      for early recurrence were analyzed. RESULTS: After a median follow-up of 33.3
      months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The
      1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-,
      3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha
      fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple
      tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR
      2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence
      (recurrence-free time <= 1-year) of HCC meeting Milan criteria. CONCLUSIONS: AFP
      > 800 ng/ml, multiple tumors and microvascular invasion are independent risk
      factors affecting early postoperative recurrence of HCC. In addition resection
      appears capable of replacing liver transplantation in some situations with safety
      and a better outcome.

PMID- 24460259
TI  - Clinical impact of palliative treatment using octreotide for inoperable malignant
      bowel obstruction caused by advanced urological cancer.
AB  - Malignant bowel obstruction (MBO), an occasional complication in patients with
      advanced urological cancer, causes gastrointestinal symptoms such as nausea and
      vomiting leading to suffering which severely impairs quality of life (QOL). Drug
      therapy, especially octreotide, a synthetic analog of somatostatin, is reportedly
      effective in controlling the symptoms of MBO. In the present study, we
      administered octreotide to urological cancer patients with MBO and evaluated the
      improvement of subjective symptoms, oral intake, and nasogastric intubation.
      Fourteen terminally ill urological cancer patients suffering with MBO were
      included (age range 55-92, 10 male, 4 female). Octreotide was administered at
      300MUg/day to those patients subcutaneously as a continuous injection.
      Significant improvements in subjective symptoms were observed in thirteen
      patients (92.8%), and ten patients (71.4%) were able to resume oral intake. Four
      patients required nasogastric drainage before the administration of octreotide,
      but nasogastric intubation was discontinued in all these cases after the use of
      octreotide. Early initiation of octreotide resulted in better improvement of MBO
      symptoms, and no adverse event was observed in any of the patients. These results
      revealed that 300MUg/day dose of octreotide is safe and effective for managing
      gastrointestinal symptoms of terminally ill urological cancer patients with MBO.
      We also recommend starting the treatment with ocreotide as soon as MBO is
      diagnosed. 

PMID- 24460260
TI  - Efficacy and safety of Trastuzumab added to standard treatments for HER2-positive
      metastatic breast cancer patients.
AB  - INTRODUCTION: Trastuzumab, an HER2-targeting agents, has shown efficacy in
      metastatic HER2-positive breast cancer patients. Single-agent clinical trials
      have evaluated therapeutic regimens using trastuzumab for metastatic breast
      cancer patients. The aim of our study is to evaluate the efficacy and safety of
      trastuzumab in combination with chemotherapy or hormone therapy in HER2-positive
      metastatic breast cancer patients. METHODS: A literature research was conducted
      in PubMed and to identify appropriate studies from relevant reviews. Randomized
      controlled trials comparing chemotherapy or hormone therapy regimens in
      combination with trastuzumab were eligible. Dadta on clinical outcomes, including
      safety, efficacy, and patient characteristics were collected. RESULTS: Seven
      articles describing five trials were included in our systematic review and meta-
      analysis. Partners of trastuzumab included in trials were anthracycline,
      paclitaxel, docetaxel, anastrozole and letrozole. The addition of trastuzumab to
      chemotherapy improved the overall survival (HR=0.79, 95%CI 0.65- 0.96), while to
      hormone therapy did not (HR=0.85 95%CI 0.56-1.30). All trastuzumab-containing
      regimens increased cardiac toxicity (RR=3.37, 95%CI 1.26-9.02) and grade III-IV
      adverse events. CONCLUSIONS: Our study supports the addition of trastuzumab to
      chemotherapy which is effective and tolerated for metastatic breast cancer with
      HER2+ patients. Of note, more adverse events will occur followed the use of
      trastuzumab, especially cardiac toxicity, with two treatment regimens.

PMID- 24460261
TI  - Racial and socioeconomic disparities in malignant carcinoid cancer cause specific
      survival: analysis of the surveillance, epidemiology and end results national
      cancer registry.
AB  - BACKGROUND: This study hypothesized living in a poor neighborhood decreased the
      cause specific survival in individuals suffering from carcinoid carcinomas.
      Surveillance, Epidemiology and End Results (SEER) carcinoid carcinoma data were
      used to identify potential socioeconomic disparities in outcome. MATERIALS AND
      METHODS: This study analyzed socioeconomic, staging and treatment factors
      available in the SEER database for carcinoid carcinomas. The Kaplan-Meier method
      was used to analyze time to events and the Kolmogorov-Smirnov test to compare
      survival curves. The Cox proportional hazard method was employed for multivariate
      analysis. Areas under the receiver operating characteristic curves (ROCs) were
      computed to screen the predictors for further analysis. RESULTS: There were
      38,546 patients diagnosed from 1973 to 2009 included in this study. The mean
      follow up time (S.D.) was 68.1 (70.7) months. SEER stage was the most predictive
      factor of outcome (ROC area of 0.79). 16.4% of patients were un-staged.
      Race/ethnicity, rural urban residence and county level family income were
      significant predictors of cause specific survival on multivariate analysis, these
      accounting for about 5% of the difference in actuarial cause specific survival at
      20 years of follow up. CONCLUSIONS: This study found poorer cause specific
      survival of carcinoid carcinomas of individuals living in poor and rural
      neighborhoods.

PMID- 24460262
TI  - Clinical application of endoscopic inguinal lymph node resection after lipolysis
      and liposuction for vulvar cancer.
AB  - AIM: To examine lymph nodes obtained after lipolysis and liposuction of
      subcutaneous fat of the inguinal region of female vulvar cancer patients to
      explore the feasibility of clinical application. METHODS: The field of operation
      was on the basis of the range of the conventional resection of inguinal lymph
      nodes. We injected lipolysis liquid fanwise, started liposuction after 15-20
      minutes; then the subcutaneous fatty tissue was sucked out clearly by suction
      tube. We selected the first puncture holes located on 2-3 cm part below anterior
      superior spine, the others respectively being located 3cm and 6cm below the first
      for puncturing into the skin, imbedding a trocar to intorduce CO2 gas and the
      specular body, and excise the lymph nodes by ultrasonic scalpel. The surgical
      field chamber was set with negative pressure drainage and was pressured with a
      soft saline bag after surgery. RESULTS: A lacuna emerged from subcutaneous of the
      inguinal region after lipolysis and liposuction, with a wide fascia easily
      exposed at the bottom where lymph nodes could be readily excised. The number of
      lymph nodes of ten patients excised within the inguinal region on each side was 4
      18. The excised average number of lymph nodes was 11 when we had mature
      technology. CONCLUSION: Most of adipose tissue was removed after lipolysis and
      liposuction of subcutaneous tissue of inguinal region, so that the included lymph
      nodes were exposed and easy to excise by endoscope. This surgery avoided the
      large incision of regular surgery of inguinal region, the results indicating that
      this approach is feasible and safe for used as an alternative technology.

PMID- 24460263
TI  - RPSA gene mutants associated with risk of colorectal cancer among the chinese
      population.
AB  - The primary aim of this study was to evaluate the relationship of single
      nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with
      colorectal cancer (CRC). A case-control study including 388 controls and 387
      patients with CRC was conducted in a Chinese population. Information about socio
      demography and living behavior factors was collected by a structured
      questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were
      genotyped by Illumina SnapShot method. Multiple logistic regression models were
      used for assessing the joint effects between tea consumption and SNPs on CRC. The
      subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI
      = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A
      similar association of rs2269349 with rectal cancer was observed (OR=0.49;
      95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the
      protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT
      or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and
      95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea
      drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA
      gene might be associated with genetic susceptibility to CRC and influence the
      protective effect of tea consumption in the Chinese population. 

PMID- 24460264
TI  - Assessing the impact of socio-economic variables on breast cancer treatment
      outcome disparity.
AB  - BACKGROUND: We studied Surveillance, Epidemiology and End Results (SEER) breast
      cancer data of Georgia USA to analyze the impact of socio-economic factors on the
      disparity of breast cancer treatment outcome. MATERIALS AND METHODS: This study
      explored socio-economic, staging and treatment factors that were available in the
      SEER database for breast cancer from Georgia registry diagnosed in 2004-2009. An
      area under the receiver operating characteristic curve (ROC) was computed for
      each predictor to measure its discriminatory power. The best biological
      predictors were selected to be analyzed with socio-economic factors. Survival
      analysis, Kolmogorov- Smirnov 2-sample tests and Cox proportional hazard modeling
      were used for univariate and multivariate analyses of time to breast cancer
      specific survival data. RESULTS: There were 34,671 patients included in this
      study, 99.3% being females with breast cancer. This study identified race and
      education attainment of county of residence as predictors of poor outcome. On
      multivariate analysis, these socio-economic factors remained independently
      prognostic. Overall, race and education status of the place of residence
      predicted up to 10% decrease in cause specific survival at 5 years. CONCLUSIONS:
      Socio-economic factors are important determinants of breast cancer outcome and
      ensuring access to breast cancer treatment may eliminate disparities.

PMID- 24460265
TI  - Inhibition of nemo-like kinase increases taxol sensitivity in laryngeal cancer.
AB  - Several studies have shown that nemo-like kinase (NLK) plays a vital role in
      apoptosis of cancer cells. The present research concerned effects and mechanisms
      of Taxol on NLK knockdown human laryngeal cancerHep-2 cell lines in vitro. Using
      RNAi, methyl-thiazoltetrazolium (MTT) assays, real-time RT-PCR, Western blotting
      and flow cytometry analysis, growth and the cell cycle progression of NLK
      knockdown Hep-2 cells and expression of downstream molecules were observed. Cell
      growth was obviously suppressed in the Taxol treated group (P<0.001, 48 hours).
      Cell numbers of combined Taxol-based chemotherapy with lentivirus mediated RNAi
      treatment group (Lv-shNLK+Taxol goup) were significantly different from NLK
      specific siRNA lentivirus infected group (Lv-shNLK group) (p<0.001). Flow
      cytometry analysis revealed that Lv-shNLK+Taxol caused the G0/G1-phase DNA
      content to decrease from 44.1 to 3.33% (p<0.001) and the S-phase DNA content to
      increase from 38.4 to 82.0% (p<0.001), in comparison with the Lv-shNLK+Taxol
      group. Immunoblot analysis showed that knockdown of NLK led to significant
      reduction in the levels of cyclin D1, PCNA and PARP, whereas cyclin B1 was
      elevated in. Cell growth was also obviously suppressed in the Hep-2 cell line,
      knockdown of NLK making them more sensitive to Taxol treatment. NLK is expected
      to become a target of new laryngeal cancer gene therapies. 

PMID- 24460266
TI  - The decision-making journey of malaysian women with early breast cancer: a
      qualitative study.
AB  - BACKGROUND: The survival outcomes for women presenting with early breast cancer
      are influenced by treatment decisions. In Malaysia, survival outcome is generally
      poor due to late presentation. Of those who present early, many refuse treatment
      for complementary therapy. OBJECTIVE: This study aimed to explore the decision
      making experiences of women with early breast cancer. MATERIALS AND METHODS: A
      qualitative study using individual in-depth interviews was conducted to capture
      the decision making process of women with early breast cancer in Malaysia. We
      used purposive sampling to recruit women yet to undergo surgical treatment. A
      total of eight participants consented and were interviewed using a semi
      structured interview guide. These women were recruited from a period of one week
      after they were informed of their diagnoses. A topic guide, based on the Ottawa
      decision support framework (ODSF), was used to facilitate the interviews, which
      were audio recorded, transcribed and analysed using a thematic approach. RESULTS:
      We identified four phases in the decision-making process of women with early
      breast cancer: discovery (pre-diagnosis); confirmatory ('receiving bad news');
      deliberation; and decision (making a decision). These phases ranged from when
      women first discovered abnormalities in their breasts to them making final
      surgical treatment decisions. Information was vital in guiding these women.
      Support from family members, friends, healthcare professionals as well as
      survivors also has an influencing role. However, the final say on treatment
      decision was from themselves. CONCLUSIONS: The treatment decision for women with
      early breast cancer in Malaysia is a result of information they gather on their
      decision making journey. This journey starts with diagnosis. The women's spouses,
      friends, family members and healthcare professionals play different roles as
      information providers and supporters at different stages of treatment decisions.
      However, the final treatment decision is influenced mainly by women's own
      experiences, knowledge and understanding.

PMID- 24460267
TI  - Common variants in the PALB2 gene confer susceptibility to breast cancer: a meta
      analysis.
AB  - OBJECTIVE: Increasing scientific evidence suggests that common variants in the
      PALB2 gene may confer susceptibility to breast cancer, but many studies have
      yielded inconclusive results. This meta-analysis aimed to derive a more precise
      estimation of the relationship between PALB2 genetic variants and breast cancer
      risk. METHODS: An extensive literary search for relevant studies was conducted in
      PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar,
      CNKI and CBM databases from their inception through September 1st, 2013. A meta
      analysis was performed using the STATA 12.0 software and crude odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated. RESULTS: Six case-control
      studies were included with a total of 4,499 breast cancer cases and 6,369 healthy
      controls. Our meta-analysis reveals that PALB2 genetic variants may increase the
      risk of breast cancer (allele model: OR>1.36, 95%CI: 1.20~1.52, P < 0.001;
      dominant model: OR>1.64, 95%CI: 1.42~1.91, P < 0.001; respectively). Subgroup
      analyses by ethnicity indicated PALB2 genetic variants were associated with an
      increased risk of breast cancer among both Caucasian and Asian populations (all P
      < 0.05). No publication bias was detected in this meta-analysis (all P > 0.05).
      CONCLUSION: The current meta-analysis indicates that PALB2 genetic variants may
      increase the risk of breast cancer. Thus, detection of PALB2 genetic variants may
      be a promising biomarker approach.

PMID- 24460268
TI  - Intra-operative rectal washout with saline solution can effectively prevent
      anastomotic recurrence: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Rectal washout with saline solution may theoretically
      prevent anastomotic recurrence in patients with resectable rectal cancer,
      although exact clinical effects have not yet been determined. In order to derive
      a more precise estimation of the relationship, the present meta-analysis was
      performed. METHOD: Relevant studies were identified by a search of Medline,
      Embase and Google Website with no restrictions to September 1, 2013, and included
      in the systematic review and meta-analysis. RESULTS: 5 trials (642 participants)
      were included to assess the association between rectal washout with saline
      solution and anastomotic recurrence. The rate of anastomotic recurrence (AR) was
      6.23% (40/642), with the pooled OR derived from the five studies being 0.32 (95 %
      CI=0.15-0.70, P=0.004). The pooled OR derived from the TME and radical resection
      subgroups were 0.72 (95%CI=0.16-3.12, P=0.66) and 0.51 (95%CI=0.13-1.96, P=0.32),
      respectively. CONCLUSION: Results from this analysis show that intra-operative
      rectal washout with mere saline solution largely reduces the risk of anastomotic
      recurrences in patients with resectable rectal cancer.

PMID- 24460269
TI  - Breast cancer awareness of rural women in Malaysia: is it the same as in the
      cities?
AB  - Breast cancer is the most common cancer among women globally. This study was
      conducted to compare the awareness of breast cancer and the practice of breast
      self-examination (BSE), clinical breast examination (CBE) and mammography
      screening among rural females in Pahang and Perak. A cross-sectional study was
      carried out in five selected rural districts of Pahang and Perak. Two hundred and
      fifty households were randomly selected and interviewed face to face using a semi
      structured questionnaire. The majority of residents from both states were Malay,
      aged between 50 and 60 years and had a secondary level of education. Malay women
      aged 40-49 years and women with a higher level of education were significantly
      more aware of breast cancer (p<0.05). About half of these women practiced BSE
      (60.7%) and CBE (56.1%), and 7% had underwent mammography screening. The results
      of this study suggest that women in Pahang and Perak have good awareness of
      breast cancer and that more than half practice BSE and CBE. The women's level of
      education appears to contribute to their level of knowledge and health behaviour.
      However, more effort is needed to encourage all women in rural areas to acquire
      further knowledge on breast cancer. 

PMID- 24460270
TI  - Glutathione-S-transferase (GSTM1, GSTT1) null phenotypes and risk of lung cancer
      in a Korean population.
AB  - PURPOSE: The aim of this study was to evaluate any association of GSTM1 and GSTT1
      null genotypes with the risk of lung cancer in a South Korean population.
      METHODS: We conducted a large-scale, population-based case-control study
      including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and
      GSTT1 were determined using real-time polymerase chain reaction. RESULTS: In
      logistic regression analysis adjusted for age and smoking, we did not find any
      association between GSTM1 or GSTT1 and LC risk in women. However, in men, the
      GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95%
      CI=0.99-1.41 for GSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1
      and GSTT1 null genotypes conferred an increased risk for LC in men (OR=1.39, 95%
      CI=1.08-1.78). The OR for the GSTT1 null genotype was greater in subjects aged 55
      years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97
      1.90 for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men;
      OR=0.86, 95% CI=0.66-1.12 for women) in both genders (p for interaction <0.05).
      CONCLUSIONS: In the Korean population, the GSTM1 and GSTT1 null genotypes are
      risk factors for LC in men; the GSTT1 null genotype has a more prominent effect
      on LC risk in younger people (age 55 years and under) than in older individuals.

PMID- 24460271
TI  - Comparison of efficacy and toxicity of first line chemotherapy with or without
      epirubicin for patients with advanced stage soft tissue sarcoma.
AB  - PURPOSE: To compare the safety and efficacy of first-line chemotherapy regimen
      with or without doxorubicin in treating patients with advanced soft tissue
      sarcoma (STS). PATIENTS AND METHODS: We retrospectively analyzed a cohort of 56
      patients histologically confirmed with STS who were treated at Jiangsu Cancer
      Hospital and Research Institute from July 2011 to June 2012.The basic element of
      first line chemotherapy contained epirubicin in group B and lacked epirubicin in
      group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was
      used to estimate progress free survival (PFS). RESULTS: According to RECIST
      criteria , patients in group treated by chemotherapy without epirubicin, the
      objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate
      (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2
      patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%)
      in 6. In group B with epirubicin based regimens, no patient had complete
      response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13
      patients (52%). By Fisher's exact test, the DCR difference between the two groups
      was statistically significant (p=0.046). In group A, median PFS was 3.0 months
      (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03- 4.97) in group B
      (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance
      status 0-1 were identified as favorable factors for progression in our cohort of
      patients. Differences of nonhematologic and hematologic toxicities were not
      statistically significant between the two groups, and the addition of epirobicin
      was not associated with cardiac toxicity (p=0.446). CONCLUSION: Our study
      demonstrates that epirubicin-based chemotherapy is effective and well tolerated,
      and is superior to chemotherapy without epirubicin regarding efficacy. Therefore
      it is recommended that epirubicin-based chemotherapy should be considered as
      first line for patients with advanced STS.

PMID- 24460272
TI  - Scutellaria extract decreases the proportion of side population cells in a
      myeloma cell line by down-regulating the expression of ABCG2 protein.
AB  - BACKGROUND AND AIMS: Scutellaria is one of the most popular traditional Chinese
      herbal remedies against various human diseases, including cancer. In this study,
      we examined the active effects of Scutellaria extract and its main flavonoid
      constituents on the proportion of side population cells within human multiple
      myeloma cell line RPMI8226 in vitro and explored the potential molecular
      mechanisms involved. MATERIALS AND METHODS: The contents of flavonoids in
      ethanolic extract of Scutellaria baicalensis Georgi were determined using high
      performance liquid chromatography. The antiproliferative effect of the ethanolic
      extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by
      annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis
      was performed by propidium iodide staining in combination with flow cytometry
      analysis. Hoechst 33342 exclusion assay was used for the identification of side
      population within RPMI8226 cells. The expression of ABCG2 protein was assessed by
      Western blotting assay. RESULTS: The content of major flavonoids constitutents of
      Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%),
      and wogonin (0.99%), respectively. The crude Scutellaria extract did not show
      significant anti-proliferative effect, apoptosis induction and cell cycle arrest
      in RPMI-8226 within the concentrations of 1-75MUg/mL. However, the ethanolic
      extract, baicalein, wogonin and baicalin reduced the side population cells in
      RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory
      effects. Correspondingly, they also exhibited significant effects on decreasing
      the expression level of ABCG2 protein in RPMI-8226 in vitro. CONCLUSIONS: Our
      results for the first time demonstrated a novel mechanism of action for
      Scutellaria extract and its main active flavonoids, namely targeting SP cells by
      modulating the expression of ABCG2 protein. This study provides an insight for
      new therapeutic strategies targeting cancer stem cells of multiple myeloma.

PMID- 24460273
TI  - Expression of CYP1A1 and GSTP1 in human brain tumor tissues in Pakistan.
AB  - Most of the exogenous and endogenous chemical compounds are metabolized by
      enzymes of xenobiotic processing pathways, including the phase I cytochrome p450
      species. Carcinogens and their metabolites are generally detoxified by phase II
      enzymes like glutathione-S-transferases (GST). The balance of enzymes determines
      whether metabolic activation of pro-carcinogens or inactivation of carcinogens
      occurs. Under certain conditions, deregulated expression of xenobiotic enzymes
      may also convert endogenous substrates to metabolites that can facilitate DNA
      adduct formation and ultimately lead to cancer development. In this study, we
      aimed to test the association between deregulation of metabolizing genes and
      brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and
      GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls
      using Western blotting. In a second part of the study we analyzed protein
      expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found
      to be significantly high (p<0.001) in brain tumor as compared to the normal
      tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast,
      the expression of GSTP1 was found to be significantly low in brain tumor tissues
      as compared to the controls (p<0.02). This down regulation was significantly
      higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions.
      Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain
      tumor patients compared to controls. Statistically significant decrease in GST
      levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to
      the early tissue grades (I-II). Thus, altered expression of these xenobiotic
      metabolizing genes may be involved in brain tumor development in Pakistani
      population. Investigation of expression of these genes may provide information
      not only for the prediction of individual cancer risk but also for the prevention
      of cancer. 

PMID- 24460274
TI  - Detection of recurrence in a surveillance program for epithelial ovarian cancer.
AB  - Ovarian cancer patients need a surveillance program for the detection of tumor
      progression after completion of treatment. The methods generally consist of
      history taking, physical examination, tumor marker monitoring and imaging.
      However, the details of recurrence detection with each method are not well
      defined. To clarify this issue, ovarian cancer patients who achieved complete or
      partial responses and developed tumor progression at the follow up time between
      January 2004 and December 2010 in University Hospital Chiang Mai, Thailand, were
      reviewed. Clinical data, CA 125 level and imaging results at the tumor
      progression time were recorded and analyzed. There were 144 ovarian cancer
      patients meeting the inclusion criteria with the mean age of 51 years and 62.5%
      of them were in an advanced stage. Complete response was achieved in 89 patients
      (61.8%) after primary treatment. The median progression free survival and overall
      survival were 15.5 months and 37.5 months, respectively. Abnormal symptoms
      presented in 49.3% of the studied patients and 59.7% developed physical
      examination abnormalities. In addition, CA 125 was elevated in 89.6% while in
      74.3% of tumor progression was identified by CT-scan. Short treatment time period
      and a high level of CA 125 were significant independent prognostic factors in
      these patients. In conclusion, careful history taking, physical examination and
      monitoring of CA 125 levels are important methods for tumor progression detection
      in a surveillance program for epithelial ovarian cancer patients. 

PMID- 24460275
TI  - Effect of diallyl trisulfide on human ovarian cancer SKOV- 3/DDP cell apoptosis.
AB  - AIM: To investigate the effects of diallyl trisulfide (DT) on apoptosis of
      cisplatin (DDP)-resistant human epithelial ovarian cancer SKOV-3 cells (SKOV
      3/DDP), and the role of p53 upregulated modulator of apoptosis (PUMA). METHODS:
      SKOV-3/DDP cells were randomly divided into control, DT, DPP and DPP+DT groups,
      which were treated with DT or combined DT and DDP. All cells were incubated for
      48 h. and apoptosis rates were assessed by flow cytometry. mRNA and protein
      expression of PUMA, Bax and Bcl-2 was determined by RT-PCR and Western blot
      assays, respectively. RESULTS: Compared with control group, the apoptosis rates
      of SKOV-3/DDP cells in DT groups were obviously increased, with dose-dependence
      (P < 0.05), the mRNA and protein expressions of PUMA, Bax also being up-regulated
      (P < 0.05), while those of Bcl-2 were down-regulated (P < 0.05). Compared with DT
      groups, the apoptosis rate in the DDP+DT group was significantly increased (P <
      0.05). After knockdown of PUMA with specific siRNA, the apoptosis rate of SKOV
      3/DDP cells was obviously decreased (P < 0.05). CONCLUSION: DT can promote the
      apoptosis of SKOV-3/DDP cells with PUMA playing a critical role.

PMID- 24460276
TI  - Meta-analysis of excision repair cross-complementation group 1 (ERCC1)
      association with response to platinum- based chemotherapy in ovarian cancer.
AB  - Recent studies suggested that the ovarian cancers with negative excision repair
      cross-complementation group 1 enzyme (ERCC1) expression have a better response to
      platinum-based chemotherapy than those with positive ERCC1 expression. The
      objective of this study was to evaluate whether ERCC1 expression is associated
      with response to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed,
      Web of Science and CNKI databases were used for searching studies relating to
      ERCC1 protein expression and response to platinum-based chemotherapy in ovarian
      cancers. Statistical analysis was based on the method for a fixed effects meta
      analysis. Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1
      protein expression and response to platinum- based chemotherapy were generated.
      Publication bias was investigated with Begg's test. Five studies involving 306
      patients with ovarian cancer were included. Compared to patients with positive
      ERCC1 expression, those with negative ERCC1 expression had a better response to
      platinum-based chemotherapy. The pooled OR was 5.264 (95% CI: 2.928 - 9.464, P <
      0.001) and publication bias was not found (P = 0.904). The result was similar in
      both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1
      protein expression status is significantly associated with response to platinum
      based chemotherapy in ovarian cancers. 

PMID- 24460277
TI  - Factors associated with mammography adherence among married Chinese women in
      Yanbian, China.
AB  - BACKGROUND: Despite the efficacy of regular mammograms, the incidence and
      mortality rate of breast cancer have been increasing in China. Insufficient
      studies on the factors affecting mammography adherence in Chinese married women
      have been conducted. The purpose of the present study was to explore the factors
      associated with adherence to guidelines for regular mammography among Chinese
      married women. MATERIALS AND METHODS: The participants were recruited
      conveniently and included Chinese and Korean Chinese women who were married,
      living at Yanbian City in China. Demographic information, status regarding eight
      risk factors of breast cancer, health responsibility, and perceived
      benefits/barriers of mammography were obtained. Descriptive analyses, t-test, and
      multivariate analysis were performed. Hierarchical logistic regression was
      conducted to explore the factors associated with regular mammography adherence in
      Chinese and Korean Chinese subgroups. RESULTS: About 24% of the sample population
      was adherent in going for regular mammography. The adherent group was
      significantly more educated, had more children, and had a lower proportion
      experiencing early menarche and a greater menopausal proportion than the non
      adherent group. The final model using logistic regression analysis showed that
      being Chinese [OR=2.199 (1.224-3.951)], having no or one child [OR=4.879 (1.835
      12.976)], early menarche [OR=3.515 (1.057-11.694)], being menopausal [OR=3.120
      (0.965-10.088)], aged 40-49 [OR=2.374 (1.099-5.124)], having low education
      [OR=0.400 (0.211-0.765)], and perceiving greater benefits in doing mammography
      [OR=1.080 (1.014-1.151)] were significantly associated with mammography
      adherence, after controlling for covariates. CONCLUSIONS: Sociocultural sensitive
      intervention for minorities should be emphasized when improving the adherence of
      regular mammography. Intervention tailored for women with lower education should
      be delivered and the benefits of mammography should be propagated to women in
      rural areas of China.

PMID- 24460278
TI  - Lack of assocation of glutathione S-transferase T1 gene null and susceptibility
      to lung cancer in china: a meta-analysis.
AB  - BACKGROUND: Variation in metabolic genes is regarded as an important factor in
      processes leading to cancer. However, the effect of GSTT1 null genotype is
      divergent in the form of lung cancer. METHODS: Studies were conducted at
      different research databases from 1990 to 2013 and the total odds ratio (OR) and
      95% confidence interval (CI) were calculated for lung cancer. Review Manager 5.2
      and STATE 12 are employed. RESULTS: Total OR value is calculated from 17 articles
      with 2,118 cases and 2,915 controls. We discovered no significant increase in
      lung cancer risk among subjects carrying GSTT1 null genotype [OR = 1.15; 95% CI
      0.97-1.36] in this meta- analysis. CONCLUSION: The GSTT1 deletion polymorphism
      does not have a significant effect on the susceptibility to lung cancer overall
      in China.

PMID- 24460279
TI  - Comprehensive bioinformation analysis of the mRNA profile of fascin knockdown in
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Fascin, an actin-bundling protein forming actin bundles including
      filopodia and stress fibers, is overexpressed in multiple human epithelial
      cancers including esophageal squamous cell carcinoma (ESCC). Previously we
      conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC.
      METHOD: In this study, the differentially expressed genes from mRNA expression
      profilomg of fascin knockdown were analyzed by multiple bioinformatics methods
      for a comprehensive understanding of the role of fascin. RESULTS: Gene Ontology
      enrichment found terms associated with cytoskeleton organization, including cell
      adhesion, actin filament binding and actin cytoskeleton, which might be related
      to fascin function. Except GO categories, the differentially expressed genes were
      annotated by 45 functional categories from the Functional Annotation Chart of
      DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the
      differentially expressed genes, providing more detailed information than
      traditional pathway enrichment analysis. Two subpathways derivated from
      regulation of the actin cytoskeleton were shown. Promoter analysis results
      indicated distinguishing sequence patterns and transcription factors in response
      to the co-expression of downregulated or upregulated differentially expressed
      genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of
      the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co
      regulate the upregulated genes. CONCLUSIONS: This multiple bioinformatic analysis
      helps provide a comprehensive understanding of the roles of fascin after its
      knockdown in ESCC.

PMID- 24460280
TI  - Efficacy of a training program for long-term disease- free cancer survivors as
      health partners: a randomized controlled trial in Korea.
AB  - BACKGROUND: To determine whether the Health Partner Program is effective in
      training long-term cancer survivors to be health coaches. MATERIALS AND METHODS:
      We randomly assigned cancer survivors who were selected through a rigorous
      screening process to either the Health Partner Program or the waiting-list
      control group. The program consisted of 8 weeks of training in health management,
      leadership, and coaching. At baseline, 8, and 16 weeks, we measured primary
      outcomes using the Seven Habit Profile (SHP), the Korean Leadership Coaching
      Competency Inventory (KCCI), Ed Diner's Satisfaction with Life Scale (SWLS), and
      the Posttraumatic Growth inventory (PTGI) and secondary outcomes using the
      Hospital Anxiety and Depression Scale (HADS), the Impact of Event Scale-Revised
      (IES-R), and the Medical Outcomes Study (MOS) short form 36-item questionnaire
      (SF- 36). RESULTS: We recruited 70 subjects and randomly assigned 34 to the
      intervention group. The Sharpen the Saw habit of the SHP increased significantly
      more in intervention group than in the control group (p = 0.049), as did most
      PTGI factors. The intervention group also showed a significantly greater
      enhancement of vitality (p = 0.015) and mental health (p = 0.049) SF-36 scores
      but no improvement in KCCI, SWLS, HADS, or IES-R scores. The intervention group
      also showed a greater clinically meaningful improvement in the "Think Win-Win" of
      SHP (p = 0.043) and in the personal strength score (p = 0.025) and total score (p
      = 0.015) of the PTGI. CONCLUSIONS: Long-term cancer survivors can benefit from
      the Health Partner Program to become health coaches.

PMID- 24460281
TI  - Perception and practices of physicians in addressing the smokeless tobacco
      epidemic: findings from two States in India.
AB  - BACKGROUND: Smokeless tobacco use in South Asia is believed to be a significant
      contributor to morbidity and mortality. In India, only a few studies involving
      health educational intervention by health care providers have demonstrated
      reduction in smokeless tobacco usage. In the present study we assessed the
      cessation efforts towards smokeless tobacco by physicians in two high tobacco
      prevalence states of India. The study also identified opportunities and barriers
      for integration of tobacco cessation services in routine practices of physicians.
      MATERIALS AND METHODS: This mixed method study involved qualitative (phase I) and
      quantitative research study (phase II). In phase I, 59 in-depth interviews with
      physicians were conducted. In phase II, a quantitative study conducted among 238
      physicians. An inductive approach was followed to analyze qualitative data using
      ATLAS. Ti software. The Chi-square test was employed to test the association
      between different variables of interest using SPSS version 17. RESULTS: The
      majority of physicians related only respiratory problems and cancer with
      smokeless tobacco. Other major health effects like cardio-vascular problems, oral
      diseases, and effects on reproductive and neonatal health were recognized only by
      a few physicians. The age-group of 10-19 years was identified as most vulnerable
      to smokeless tobacco use. Less than one-third of physicians reported recording
      smokeless tobacco history of all patients. Findings indicated that less than half
      of physicians provided information on harmful health effects of smokeless tobacco
      with regard to specific diseases. CONCLUSIONS: The study revealed a low level of
      knowledge of physicians about harmful effects of tobacco and their suboptimal
      engagement in tobacco control practices. The study indicates the need of capacity
      building initiatives to equip physicians with skills in tobacco cessation.

PMID- 24460282
TI  - Tumor necrosis factor-alpha gene polymorphisms and risk of oral cancer: evidence
      from a meta-analysis.
AB  - Numerous studies have been conducted regarding association between TNF-alpha and
      oral cancer risk, but the results remain controversial. The present meta-analysis
      is performed to acquire a more precise estimation of relationships. Databases of
      Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI)
      were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence
      intervals (95% CIs) were calculated with fixed- or random-effect models. The
      heterogeneity assumption was assessed by I-squared test. Among the eight included
      case-control studies, all were focused on TNF-alpha-308G>A and four also
      concerned the TNF-alpha-238G>A polymorphism. It was found that oral cancer risk
      were significant decreased with the TNF-alpha-308G>A polymorphism in the additive
      genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and
      the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03,
      I2=52.4%); however, no significant association was observed in allele contrast (G
      vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic
      models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the
      TNF-alpha-238G>A polymorphism, significant associations with oral cancer risk
      were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04],
      P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI:
      [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that
      TNF-alpha polymorphisms may contribute to the risk of oral cancer. Allele G and
      the GG+GA genotype of TNF-alpha- 308G>A may decrease the risk of oral cancer,
      while allele G and the GG genotype of TNF-alpha-238G>A may cause an increase. 

PMID- 24460283
TI  - Attributable causes of liver cancer mortality and incidence in china.
AB  - OBJECTIVES: To estimate the proportion of liver cancer cases and deaths due to
      infection with hepatitis B virus (HBV), hepatitis C virus (HCV), aflatoxin
      exposure, alcohol drinking and smoking in China in 2005. STUDY DESIGN: Systemic
      assessment of the burden of five modifiable risk factors on the occurrence of
      liver cancer in China using the population attributable fraction. METHODS: We
      estimated the population attributable fraction of liver cancer caused by five
      modifiable risk factors using the prevalence data around 1990 and data on
      relative risks from meta-analyses, and large-scale observational studies. Liver
      cancer mortality data were from the 3rd National Death Causes Survey, and data on
      liver cancer incidence were estimated from the mortality data from cancer
      registries in China and a mortality/incidence ratio calculated. RESULTS: We
      estimated that HBV infection was responsible for 65.9% of liver cancer deaths in
      men and 58.4% in women, while HCV was responsible for 27.3% and 28.6%
      respectively. The fraction of liver cancer deaths attributable to aflatoxin was
      estimated to be 25.0% for both men and women. Alcohol drinking was responsible
      for 23.4% of liver cancer deaths in men and 2.2% in women. Smoking was
      responsible for 18.7% and 1.0% . Overall, 86% of liver cancer mortality and
      incidence (88% in men and 78% in women) was attributable to these five modifiable
      risk factors. CONCLUSIONS: HBV, HCV, aflatoxin, alcohol drinking and tobacco
      smoking were responsible for 86% of liver cancer mortality and incidence in China
      in 2005. Our findings provide useful data for developing guidelines for liver
      cancer prevention and control in China and other developing countries.

PMID- 24460284
TI  - Spectrum of cytological findings in fine needle aspiration cytology of breast
      lumps with histopathology correlation: experience in a tertiary care rural
      hospital in India.
AB  - To determine the pattern of disease in patients presenting with breast lumps and
      to determine the sensitivity and specificity of fine needle aspiration cytology
      of benign and malignant diseases as a diagnostic tool by correlating with
      histopathology findings. This retrospective study was carried out in the
      Department of Pathology, Maharaja Agrasen Medical College, Agroha, from Jan 2008
      to April 2012. Fine needle aspiration cytology was performed on 370 cases and out
      of these 52 cases were received in the Department for histopathological
      examination. Fibroadenoma was the most common disease encountered, in 88 (24%),
      with a peak incidence in second and third decade of life. Fibrocystic disease was
      second, being common in the third and fourth decades of life. Peak incidences of
      duct ectasia, granulomatous and tubercular mastitis were seen in the third
      decade. Gynaecomastia showed two peak incidences in second and sixth decades of
      life . Out of total 370 cases undergoing fine needle aspiration, benign cases
      were 316 (85.4%), malignant and suspicious were 54 (14.6%) and 10 (2.70%)
      respectively. Out of total 22 histological confirmed malignant lesions 19 were
      interpreted as malignant cytologically while two as suspicious and one as benign.
      All thirty histologically confirmed benign cases were diagnosed as benign
      cytologically. The sensitivity, specificity, positive and negative predictive
      values were 98%, 100%, 100% and 96.4% respectively. FNA cytology is highly
      accurate for diagnosis of breast masses. However, the clinician should correlate
      FNA cytological results with physical examination and imaging findings to prevent
      false negative and false positive events and to obtain optimal management of
      their patients. 

PMID- 24460285
TI  - Molecular investigation of isocitrate dehydrogenase gene (IDH) mutations in
      gliomas: first report of IDH2 mutations in Indian patients.
AB  - Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly
      in grade II-III gliomas and secondary glioblastomas which are associated with
      favorable clinical outcome. These mutations have become molecular markers of
      significant diagnostic and prognostic relevance in the assessment of human
      gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32
      gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H
      mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations.
      The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%),
      and it was significantly higher in younger patients. Histological analyses
      demonstrated presence of necrosis and micro vascular proliferation in 69% and 75%
      respectively. Interestingly, IDH1 mutations were predominantly present in non
      necrotic tumors as well as in cases showing microvascular proliferation. Of the
      six IDH1 positive cases, three were glioblastomas (IV), and one each were
      anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and
      diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian
      glioma patients while IDH2 mutations are not observed. Since IDH mutations are
      associated with good prognosis, their use in routine clinical practice will
      enable better risk stratification and management of glioma patients. 

PMID- 24460286
TI  - New insights into 4-amino-2-tri-fluoromethyl-phenyl ester inhibition of cell
      growth and migration in the A549 lung adenocarcinoma cell line.
AB  - OBJECTIVE: The present study was designed to investigate the probable mechanisms
      of synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition
      of the proliferation and migration of A549 human lung carcinoma cells. MATERIALS
      AND METHODS: After the A549 cells were treated with different concentrations of
      ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were
      performed to assess migration. Immunofluorescence was used to determine the
      distribution of CAV1 and RXRalpha, while expression of CAV1, MLCK, MLC, P38, and
      phosphorylation of MLC and P38 were detected by Western blotting. RESULTS: ATPR
      could block the migration of A549 cells. The relative migration rate of ML-7
      group had significantly decreased compared with control group. In addition, ATPR
      decreased the expression of a migration related proteins, MLCK, and
      phosphorylation of MLC and P38. ATPR could also influence the expression of RARs
      or RXRs. At the same time, CAV1 accumulated at cell membranes, and RXRalpha
      relocated to the nucleus after ATPR treatment. CONCLUSIONS: Caveolae may be
      implicate in the transport of ATPR to the nucleus. Change in the expression and
      distribution of RXRalpha may be implicated in ATPR inhibition of A549 cell
      proliferation. The mechanisms of ATPR reduction in A549 cell migration may be
      associated with expression of MLCK and phosphorylation of MLC and P38.

PMID- 24460287
TI  - Lack of any association between insertion/deletion (I/D) polymorphisms in the
      angiotensin-converting enzyme gene and digestive system cancer risk: a meta
      analysis.
AB  - OBJECTIVE: To investigate the association between the gene polymorphisms of
      angiotensin-converting enzyme (ACE) and digestive system cancer risk. METHOD: A
      search was performed in Pubmed, Medline, ISI Web of Science and Chinese
      Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical
      analysis was performed by using Revman5.2 and STATA 12.0. RESULTS: A total of 15
      case-control studies comprising 2,390 digestive system cancer patients and 9,706
      controls were identified. No significant association was found between the I/D
      polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53
      for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no
      significant associations were found for the comparison of DD+DI vs. II. Results
      from other comparative genetic models also indicated a lack of associations
      between this polymorphism and digestive system cancer risks. CONCLUSIONS: This
      meta-analysis suggested that the ACE D/I polymorphism might not contribute to the
      risk of digestive system cancer.

PMID- 24460288
TI  - Clinico-pathology of lung cancer in a regional cancer center in Northeastern
      India.
AB  - BACKGROUND: Globally, there have been important changes in trends amongst gender,
      histology and smoking patterns of lung cancer cases. MATERIALS AND METHODS: This
      retrospective study was conducted on 466 patients with lung cancer who were
      registered in Regional Cancer Center, Regional Institute of Medical Sciences,
      Manipur from January 2008 to December 2012. RESULTS: Most were more than 60 years
      of age (67.8%) with a male: female ratio of 1.09:1. Some 78.8% of patients were
      chronic smokers with male smoker to female smoker ratio of 1.43:1. Consumption of
      alcohol was found in 29.4%, both smoking and alcohol in 27.5%, betel nut chewing
      in 37.9% and tobacco chewing in 25.3%. A history of tuberculosis was present in
      16.3% of patients. The most frequent symptom was coughing (36.6%) and most common
      radiological presentation was a mass lesion (70%). Most of the patients had
      primary lung cancer in the right lung (60.3%). The most common histological
      subtype was squamous cell carcinoma (49.1%), also in the 40-60 year age group
      (45.9%), more than 60 year age group (51.6%), males (58.1%) and females (41.8%).
      As many as 91.9% of squamous cell carcinoma patients had a history of smoking.
      About 32.5% of patients had distant metastasis at presentation with brain (23.8%)
      and positive malignant cells in pleural effusions (23.1%) as common sites. The
      majority of patients were in stage III (34.4%), stage IV (32.5%) and stage II
      (30.2%). CONCLUSIONS: Our analysis suggests that the gender gap has been narrowed
      such that about half of the patients diagnosed with lung cancer are women in this
      part of India. This alarming rise in female incidence is mainly attributed to an
      increased smoking pattern. Squamous cell carcinoma still remains the commonest
      histological subtype. Most of the patients were elderly aged and presented at
      locally or distantly advanced stages.

PMID- 24460289
TI  - Refusal self efficacy, self esteem, smoking refusal skills and water pipe
      (Hookah) smoking among iranian male adolescents.
AB  - BACKGROUND: Tobacco use among adolescents is a major public health concern, and
      identifying predictors of smoking is necessary for planning prevention programs.
      The present study examined the relationship between refusal self efficacy, self
      esteem, smoking refusal skills and water pipe (hookah) smoking among Iranian male
      adolescents. MATERIALS AND METHODS: A cross-sectional study was conducted with
      380 Iranian male adolescents aged between 15-19 years selected by multistage
      sampling. The participants completed an anonymous, voluntary, self-report
      questionnaire. Variables independently associated with water pipe (WP) smoking
      were identified by multiple logistic regression analysis. RESULTS: The mean age
      of the participants was 16.7+/-1.3 years. The prevalence of WP smoking was 17.3%.
      Logistic regression analysis revealed that knowledge (OR=0.56; 95% CI: (0.37
      0.79), attitude (OR=0.69; 95% CI: (0.52-0.89), self esteem (OR=0.67; 95% CI:
      (0.55-0.82), smoking refusal skills (OR=0.73; 95% CI: (0.55-0.87), and self
      efficacy (OR=.82; 95% CI: (0.61-0.93) were all signifcant prediting facotrs for
      adolescents WP smoking. CONCLUSIONS: The findings have implications for public
      health interventions. Indeed, self efficacy and smoking refusal skills should be
      considered when developing tailored measures for the prevention of WP smoking
      among adolescents.

PMID- 24460290
TI  - Effective response of the peritoneum microenvironment to peritoneal and systemic
      metastasis from colorectal carcinoma.
AB  - We here document discovery of a new and simple model of tumor seeding involving
      the mouse peritoneum. Irradiated tumor cells administered by i.p. injection
      provided effective vaccination against peritoneal carcinomatosis and distal
      metastasis with colorectal carcinomas. In flow cytometric analysis, CD4 and CD8+
      T lymphocytes, macrophages and myeloid-derived suppressor cells (MDSCs), which
      are easy to obtain in the peritoneal cavity, were revealed to have significant
      differences between immunized and non-immunized mice and these contributed to
      antitumor responses. We also observed that both serum and peritoneal lavage fluid
      harvested from immunized mice showed the presence of CT26-specific
      autoantibodies. In addition, increase in level of TGF-beta1 and IL-10 in serum
      but a decrease of TGF-beta1 in peritoneum was found. Taken together, these
      findings may provide a new vaccine strategy for the prevention of peritoneal and
      even systemic metastasis of carcinomas through induction of an autoimmune
      response in the peritoneum. 

PMID- 24460291
TI  - MCPH1 Protein Expression in Normal and Neoplastic Lung Tissues.
AB  - Lung cancer is the most common cause of cancer-related death in the world. The
      main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma
      (NSCLC), the latter including squamous cell carcinoma (SCC), adenocarcinoma and
      large cell carcinoma. NSCLCs account for about 80% of all lung cancer cases.
      Microcephalin (MCPH1), also called BRIT1 (BRCT-repeat inhibitor of hTERT
      expression), plays an important role in the maintenance of genomic stability.
      Recently, several studies have provided evidence that the expression of MCPH1
      gene is decreased in several different types of human cancers. We evaluated the
      expression of protein MCPH1 in 188 lung cancer and 20 normal lung tissues by
      immunohistochemistry. Positive MCPH1 staining was found in all normal lung
      samples and only some cancerous tissues. MCPH1-positive cells were significantly
      lower in lung carcinoma compared with normal tissues. Furthermore, we firstly
      found that MCPH1 expression in lung adenocarcinoma is higher than its expression
      in squamous cell carcinoma. Change in MCPH1 protein expression may be associated
      with lung tumorigenesis and may be a useful biomarker for identification of
      pathological types of lung cancer. 

PMID- 24460292
TI  - Determinants of participation in a breast cancer screening trial in trivandrum
      district, India.
AB  - BACKGROUND: Conspicuous differences in participation rates for breast self
      examination (BSE), clinical breast examination (CBE), and referral for further
      investigations have been observed indicating involvement of a number of different
      factors. This study analysed determinants for participation in different levels
      of the breast cancer screening process in Indian females. MATERIALS AND METHODS:
      An intervention group of 52,011 women was interviewed in a breast cancer
      screening trial in Trivandrum district, India. In order to assess demographic,
      socio-economic, reproductive, and cancer-related determinants of participation in
      BSE, CBE, and referral, uni- and multi-variate logistic regression was employed.
      RESULTS: Of the interviewed women, 23.2% reported practicing BSE, 96.8% had
      attended CBE, and 49.1% of 2,880 screen-positives attended referral. Results
      showed an influence of various determinants on participation; women who were
      currently not married or who had no family history of cancer were significantly
      less likely to attend the screening process at any level. CONCLUSIONS: Increasing
      awareness about breast cancer, early detection methods, and the advantages of
      early diagnoses among women, and their families, as well as health care workers
      offering social support, could help to increase participation over the entire
      screening process in India.

PMID- 24460293
TI  - Factors associated with place of death in koprean patients with terminal cancer.
AB  - AIM: To investigate factors that affect the place of death (POD) of terminal
      cancer patients. MATERIALS AND METHODS: We recruited 702 consecutive patients
      (>18 years) from 12 centers during July 2005 to October 2006, and 481 completed
      the questionnaire. In April 2011, we linked the data for 96.0% (n=462) of the
      deceased patients to the POD using the 2005-2009 death certificate data of
      Korea's National Statistical Office. The primary outcome variable was POD, and
      the predictive value of variables pertaining to patients and caregivers was
      evaluated using univariate and multivariate analyses. RESULTS: Most patients died
      in a hospital (91.5%, n=441) and age, education, preference for place of terminal
      care, wish to use hospice/palliative care services, terminal cancer awareness,
      time between diagnosis and death, and global quality-of-life subscale of the
      EORTC QLQ-C30 of patients, and education and preference for place of terminal
      care of caregivers were significant predictors in univariate analyses. On
      multivariate analysis, patients and caregivers who preferred hospital/palliative
      care as the terminal care option over home care [adjusted odds ratio (aOR), 2.68;
      95% confidential interval (CI), 1.18- 7.04 and aOR: 2.65; 95%CI: 1.15-6.09 for
      patient and caregiver preferences, respectively] and caregivers who were highly
      educated (aOR, 3.19; 95%CI, 1.44-7.06) were predictors of POD. CONCLUSIONS: Most
      of the terminal cancer patients died in a hospital. Our findings indicate that
      major predictors of hospital deaths are preference of both the patient and
      caregiver for hospital/palliative care as the terminal care option and higher
      education of the caregiver.

PMID- 24460294
TI  - Overexpressed ostepontin-c as a potential biomarker for esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The metastasis gene osteopontin (OPN) is subject to alternative
      splicing, which yields three messages, osteopontin-a, osteopontin-b and
      osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in
      noninvasive tumors. In the present study, we examined the expression of OPN-c in
      esophageal squamous cell carcinomas (ESCCs) and assessed its value as a
      diagnostic biomarker. METHODS: OPN-c expression was assessed by
      immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic
      factors. Expression was also examined in peripheral blood mononuclear cells
      (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as
      a tumor marker was investigated by receiver operating characteristic curve (ROC)
      analysis. RESULTS: Immunohistochemistry showed that OPN-c was expressed in 30 of
      63 cancer lesions (48%)and significantly associated with pathological T stage
      (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was
      expressed at higher levels in the PBMCs of ESCC patients than in those of healthy
      subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. CONCLUSION:
      Our findings suggest that expression of OPN-c is significantly elevated in ESCCs
      and this upregulation could be a potential diagnostic marker.

PMID- 24460295
TI  - Pancreatic cancer incidence and mortality patterns in china, 2009.
AB  - OBJECTIVE: To estimate the incidence and mortality rates for pancreatic cancer in
      China. METHODS: After checking and reviewing the cancer registry data in 2009
      from 72 cancer registry centers, we divided cancer registry areas into urban and
      rural areas. Incidence/mortality rates, age-specific incidence/mortality rates,
      age- standardized incidence/mortality rates, proportions, and cumulative
      incidence/mortality rates for pancreatic cancer were calculated. RESULTS: The
      total number of newly diagnosed pancreatic cancer cases and deaths in 2009 were
      6,220 and 5,650, respectively. The crude incidence rate in all cancer registry
      areas was 7.28/100,000 (males 8.24, females 6.29). The age-standardized incidence
      rate by Chinese standard population (ASR) was 3.35/100,000, with ranking at 7th
      among all cancers. Pancreatic cancer incidence rate was 8.19/100,000 in urban
      areas whereas it was 5.41/100 000 in rural areas. Cancer mortality rate in all
      cancer registry areas was 6.61/100,000 (males 7.45; females 5.75), with ranking
      at 6th among all cancers, and 7.42/100 000 in urban but 4.94/100000 in rural
      areas. CONCLUSIONS: Pancreatic cancer incidence and mortality rates have shown a
      gradual increase in China. Owing to the difficulty of early diagnosis,
      identification of high-risk population and modification of risk factors are
      important to reduce the burden of pancreatic cancer.

PMID- 24460296
TI  - Knowledge and attitudes about human papillomaviruses and immunization among
      Turkish pediatricians.
AB  - BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually
      transmitted infectious agents, and the effectiveness of vaccine delivery programs
      will depend largely upon whether providers recommend vaccines. The objectives of
      this study were to examine pediatrician characteristics, knowledge, and attitudes
      associated with HPV and HPV immunization. MATERIALS AND METHODS: Attendees of the
      national pediatric meeting in 2011, were asked to complete a questionnaire that,
      aside from demographic information, elicited level of agreement with statements
      regarding HPV, its related diseases, and HPV vaccination. It also documented
      attitudes and beliefs about HPV vaccination. RESULTS: Of the 480 attendees, 226
      (47%) filled in the questionnaire. The level of pediatrician HPV-related
      knowledge varied. The majority (78%) were aware that HPV infection is the most
      common sexually transmitted infection, while 51% were unaware that a condom is
      ineffective protection against HPV infection. Between 60-80% of respondents were
      aware of the effectiveness of HPV vaccination for women. On the other hand, only
      10% were aware of reasons why men should be vaccinated against HPV. The majority
      (75%) of Turkish pediatricians were likely to recommend HPV vaccination to their
      daughter, if they had one. Seventy percent of pediatricians agreed that the HPV
      vaccination should be added to the National Immunization Program (NIP) in Turkey.
      However, the respondents documented concerns about the cost of the vaccination.
      CONCLUSIONS: Increasing pediatricians' knowledge and awareness of HPV and HPV
      vaccination may assist with the implementation of an effective NIP.

PMID- 24460297
TI  - Elevated serum insulin is an independent risk factor for hepatocellular
      carcinoma: a case control study from Nepal.
AB  - AIM: To investigate associations of fasting insulin and glucose levels in serum
      with hepatocellular carcinoma risk. MATERIALS AND METHODS: This hospital based
      study was carried out using data retrieved from the register maintained in the
      Department of Biochemistry of the Nepalese Army Institute of Health Sciences,
      between 1st December, 2011 and 31st June, 2013. The variables collected were age,
      fasting plasma glucose, fasting plasma insulin and ALT. Quantitative
      determination of human insulin concentrations was accomplished by
      chemiluminescence enzyme immunoassay. RESULTS: Of the total 220 subjects enrolled
      in our present study, 20 cases were of HCC and 200 were healthy controls. The
      maximum number of cases of hepatocellular carcinoma in category cutpoints of
      fasting insulin levels fell in the range of >6.10 MUU/ml. The highest insulin
      levels (>6.10 MUU/ml) were seen to be associated with an 2.36 fold risk of HCC
      when compared with fasting insulin levels of (<2.75 MUU/ml). Furthermore, the
      insulin levels (2.75-4.10 MUU/ml) of category cutpoints also conferred a 1.57
      fold risk for HCC when compared with lowest fasting insulin levels of (<2.75
      MUU/ml). CONCLUSIONS: The effect of an insulin level in increasing HCC risk
      appeared consistent, influencing incidence, risk of recurrence, overall survival,
      and treatment-related complications in HCC patients.

PMID- 24460298
TI  - HPV16 CTL epitope peptide-activated dendritic cell and natural killer co-culture
      for therapy of cervical cancer in an animal model.
AB  - There is increasing evidence that natural killer (NK) cells play an important
      role in antitumor immunity following dendritic cell (DC) vaccination. Little is
      known, however, about the optimal stimulation of DCs by epitopes and NK
      interactions for cytotoxicity in tumors. In this study, DC cells activated by the
      HPV16E7.49-57 epitope and LPS were co-cultured with NK cells in vitro, and then
      used ot immunize mice to study CTL activity of TC-1, which constitutively
      expresses HPV16E6E7, with an LDH release assay. Cytotoxicity in mice immunized
      with DC loaded with epitope HPVE7.49-57 vaccine co-cultured with NK was enhanced
      significantly (p<0.01). In conclusion, talk-across between DC and NK cells
      enhances their functions, also improving cytotoxicity againsttumor cells,
      suggesting that activated DC-NK by epitopes has potential application for cancer
      specific immuno-cellular therapy. 

PMID- 24460299
TI  - Fused polypeptide with DEF induces apoptosis of lung adenocarcinoma cells.
AB  - To analyze the effects of a new unknown peptide DEF on the growth of tumor cells,
      a fused polypeptide TAT-DV1-DEF was designed and synthesized. The lung
      adenocarcinoma cell line GLC-82 treated with TAT- DV1-DEF was analyzed with a
      cell counting kit 8, and the location of polypeptides in cells was observed under
      laser confocal microscopy. The efficiency of polypeptide transfection and changes
      in nuclear morphology were analyzed by flow cytometry and fluorescence
      microscopy, respectively. Finally, the mechanism of tumor cell growth inhibition
      was evaluated by Western blotting. We found that TAT-DV1-DEF could significantly
      inhibit the growth of the lung adenocarcinoma cell line GLC-82, but not the
      normal human embryonic kidney cell line HEK-293. Polypeptides were found to be
      mostly localized in the cytoplasm and some mitochondria. The efficiency of
      polypeptide transfection in the two cell types was approximately 99%. Apoptotic
      nuclei were observed under fluorescence microscopy upon treatment with
      polypeptides and DAPI staining. Western blot analyses indicated that the
      polypeptide inhibition of tumor cell growth was apoptosis dependent. In the
      present study, we demonstrated that fused polypeptides could induce apoptosis of
      the lung adenocarcinoma cell line GLC-82, indicating that the new unknown peptide
      DEF has antitumor effects. 

PMID- 24460300
TI  - Can Glypican3 be diagnostic for early hepatocellular carcinoma among Egyptian
      patients?
AB  - BACKGROUND: Because of the high prevalence of hepatocellular carcinoma (HCC) in
      Egypt, new markers with better diagnostic performance than alpha-feto protein
      (AFP) are needed to help in early diagnosis. The aim of this work was to compare
      the clinical utility of both serum and mRNA glypican3 (GPC3) as probable
      diagnostic markers for HCC among Egyptian patients. MATERIALS AND METHODS: A
      total of 60 subjects, including 40 with HCC, 10 with cirrhosis and 10 normal
      controls were analyzed for serum GPC3 (sGPC3) by ELISA. GPC-3 mRNA from
      circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both
      markers were compared to some prognostic factors of HCC, and sensitivity of both
      techniques was compared. RESULTS: Serum glypican-3 and AFP were significantly
      higher in the HCC group compared to cirrhotic and normal controls (p<0.001).
      Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for
      AFP, and (100% and 90%) for Glypican3 mRNA , and (80% and 95%) for double
      combination between sGPC3 and AFP respectively. CONCLUSION: Both serum GPC-3 and
      GPC-3mRNA are promising diagnostic markers for early detection of HCC in Egyptian
      patients. RT- PCR proved to be more sensitive (100%) than ELISA (95%) in
      detecting glypican3.

PMID- 24460301
TI  - Renal cell carcinoma is more aggressive in Turkish patients with the metabolic
      syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a multifactorial disease characterized
      by impaired glucose tolerance/diabetes, obesity, high triglyceride levels, low
      HDL levels, and hypertension. In this study we evaluate the relationship between
      tumor size and grade, and presence of the metabolic syndrome in patients with
      renal cell carcinoma. MATERIALS AND METHODS: Between 2007-2013, radical
      nephrectomy was performed for 310 patients with renal tumors in our clinic and
      those with pathology reported renal cell carcinoma were enrolled and divided into
      two groups, with and without metabolic syndrome diagnosed on the basis of the
      National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III)
      criteria. The relationship between tumor size and grade of the two groups
      (Fuhrman nuclear degree) was evaluated statistically. RESULTS: The metabolic
      syndrome was found in 70 patients, with a mean age of 65.5 (40-87), as compared
      to 58.8 (31-84) years in the non-metabolic syndrome group. Tumor size over 7 cm
      was found in 54% and 33%, respectively, and tumor grade over Fuhrman 3 in 56% and
      32% of patients. Patients with metabolic syndrome had significantly higher tumor
      size and grade (p<0.05). In the presence of hypertension, diabetes and high
      triglyceride levels, significant assocations were again observed (p<0.05). Tumor
      size and degree also increased with increasing body mass index but this was not
      statistically significant (p>0.05). CONCLUSIONS: Renal cancer is more aggressive
      in patients with metabolic syndrome. Lifestyle and risk factors were revealed to
      be significant influences in renal cancer patients.

PMID- 24460302
TI  - Lack of association of common polymorphisms in MUC1 gene with H. pylori infection
      and non-cardia gastric cancer risk in a Chinese population.
AB  - Several lines of evidence support the notion that MUC1 is often aberrantly
      expressed in gastric cancer, and it is a ligand for Helicobacter pylori. Genetic
      variation in MUC1 gene may confer susceptibility to H. pylori infection and
      gastric cancer. We assessed the association of common polymorphisms in MUC1 gene
      with H. pylori infection and non-cardia gastric cancer using an LD-based tag SNP
      approach in north-western Chinese Han population. A total of four SNPs were
      successfully genotyped among 288 patients with non-cardia gastric cancer and 281
      age- and sex-matched controls. None of the tested SNPs was associated with H.
      pylori infection. SNP rs9426886 was associated with a decreased risk of non
      cardia gastric cancer, but lost significance after adjustment for multiple
      testing. Overall, our data indicated that common genetic variations in MUC1 gene
      might not make a major contribution to the risk of H. pylori infection and non
      cardia gastric cancer in our studied population. 

PMID- 24460303
TI  - Perioperative comprehensive supportive care interventions for chinese patients
      with esophageal carcinoma: a prospective study.
AB  - OBJECTIVE: To assess the effects of perioperative comprehensive supportive care
      interventions on outcome of Chinese esophageal cancer patients in a prospective
      study. METHODS: 60 patients with primary esophageal carcinoma were randomized
      into an intervention group (IG, n=31) and a control group (CG, n=29). The Chinese
      version of symptom checklist-90 (SCL-90) was adopted to assess their
      psychological status. The interventions, including health education,
      psychological support, stress management, coping strategies and behavior
      training, were carried out in 3 phases (preoperative, postoperative I and
      postoperative II), and psychological effects were thereafter evaluated
      accordingly before surgery, and 1 week, 4 weeks and 24 weeks post-surgery.
      Medical costs were estimated at discharge. Survival of patients was estimated
      each year post-surgery. General health status and satisfaction-with-hospital were
      surveyed by a follow-up questionnaire 4 years post-surgery. RESULTS: All the
      subjects demonstrated higher scores in the preoperative phase than the normal
      range of Chinese population concerning 7 psychological domains including
      somatization, obsessive-compulsive, depression, anxiety, hostility, phobic
      anxiety and paranoid ideation. Although no significant difference was observed
      between the two groups at admission, the scores of IG, which tended to decrease
      at a faster rate, were generally lower than those of CG at weeks 1, 4 and 24 post
      surgery. The length of hospital stay and medical costs of IG were significantly
      less than those of CG and satisfaction-with-hospital was better. However, there
      was no significant difference in 4-year survival or health status between two
      groups. CONCLUSIONS: Appropriate perioperative comprehensive supportive care
      interventions help to improve the psychological state of Chinese patients with
      esophageal carcinoma, to reduce health care costs and to promote satisfaction of
      patients and their families with hospital.

PMID- 24460304
TI  - Efficiency and side effects of sorafenib therapy for advanced hepatocellular
      carcinoma: a retrospective study by the anatolian society of medical oncology.
AB  - BACKGROUND: Inoperable and metastatic hepatocellular carcinoma (HCC) is
      associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib
      is an oral multi-kinase inhibitor exerting its effects via the RAF/ MEK/ERK
      pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived
      growth factor receptor beta (PDGFR-beta) tyrosine kinases. Randomized studies
      have shown a significant contribution of sorafenib to life expectancy and quality
      of life of cancer patients. The aim of the present study is to evaluate the
      efficacy and side effects of sorafenib therapy in Turkey. MATERIALS AND METHODS:
      Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13
      centers from February 2008 to December 2012 were evaluated. Median age was 61
      years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%)
      had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients
      (12%) had a history of alcohol consumption. All of the patients had Child scores
      meeting the utilization permit of the drug in our country (Child A). RESULTS: A
      total of 571 cycles of sorafenib therapy were administered with a median of four
      per patient. Among the evaluable cases, there was partial response in 15 (15%),
      stable disease in 52 (50%), and progressive disease in 36 (35%). Median
      progression-free survival was 18 weeks and median overall survival was 48 weeks.
      The dose was reduced only in 6 patients and discontinued in 2 patients due to
      grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%)
      diarrhea, and 2 (2%) vomiting. CONCLUSIONS: This retrospective study demonstrated
      better efficacy of sorafenib therapy in patients with advanced HCC compared to
      the literature while progression-free survival and overall survival findings were
      comparable. The side effect rates indicate that the drug was tolerated well. In
      conclusion, among the available treatment options, sorafenib is an efficient and
      tolerable agent in patients with inoperable or metastatic HCC.

PMID- 24460305
TI  - HPV vaccine knowledge and perceived risk of cervical cancer among female college
      students in Taiwan.
AB  - AIMS: The study targeted the HPV vaccine knowledge and perceived risk of cervical
      cancer among female college students in Taiwan as well as the relationship
      between knowledge of the HPV vaccine and perceived risk of cervical cancer.
      MATERIALS AND METHOD: The results of this study on female college students are
      described using descriptive and correlation designs. A convenience sampling
      approach was employed with a self-filling structured questionnaire. RESULTS: A
      total of 150 students completed the questionnaire. Values were 7.49 for the mean
      HPV vaccine knowledge scale and 18.0 for their mean perceived risk of cervical
      cancer scale. HPV vaccine knowledge was positively correlated with perceived risk
      of cervical cancer. CONCLUSIONS: The findings of this study can serve as a
      reference for future HPV prevention in Taiwan.

PMID- 24460306
TI  - Roles of GST-pi and polbeta genes in chemoresistance of esophageal carcinoma
      cells.
AB  - The main aim of this study was to investigate the roles of GST-pi and polbeta
      genes in the chemoresistance of esophageal carcinoma cells. Eukaryotic expression
      vectors containing each gene were constructed and transfected into EC9706 cells,
      and the biological effects of the two genes assessed based on a resistance index.
      We additionally investigated the in vitro and in vivo anti-resistance effects of
      GST-pi and polbeta genes using recombinant lentiviruses carrying siRNAs against
      the two genes. Our results showed that upregulation of GST-pi and polbeta genes
      suppresses chemosensitivity of esophageal carcinoma cells to cisplatin, while
      downregulation of these two genes with RNAi technology reverses this
      chemoresistance. Multi-site injection of recombinant lentivirus targeting the GST
      pi gene into transplanted cDDP tumors effectively reversed their chemoresistant
      phenotype. However, the same treatment against the polbeta gene did not lead to
      significant efficacy against chemoresistance. 

PMID- 24460307
TI  - Clinicopathologic characteristics of male breast cancer: a report of 21 cases in
      radiotherapy center of hamedan, iran.
AB  - BACKGROUND: Male breast cancer accounts for less than 1% of all cancer in men and
      only around 1% of all diagnosed breast cancer. Despite a significant raise in the
      last 25 years, it still remains a rare disease. MATERIALS AND METHODS: We
      conducted a retrospective study from 2004-2011 with 21 male breast cancer
      patients. We aimed to analyze the epidemiologic data (age, personal and family
      history), tumor characteristics (size, histological type, location, TNM stage,
      receptors), surgery, adjuvant chemotherapy and radiation therapy, hormonal
      therapy and survival (relapse, follow up, death) who reffered to our center with
      breast cancer. RESULTS: The median age was 49.2+/-14.2 years (range 30-83 years).
      A family history of breast cancer was noted in four cases. The main clinical
      complaint was a retroareolar mass in 85.7%of patients (n=18). Histologically,
      85.7% (n=18)were invasive ductal carcinoma and 4.7% (n=1) had ductal carcinoma in
      situ and 9.4% (n=2) had mixed histology including invasive medullary and ductal
      carcinoma. Hormonal therapy was delivered to 16 cases (76.1%) due to ER or PR
      positivity. During median follow up of 30 months (3-84 month), distant metastases
      were evident in 4 cases (19%). During the follow-up period, only one patient died
      due to metastatic disease. The mean time to recurrence detection was 30 months.
      CONCLUSIONS: The percentage of cases of male breast cancer is very low compared
      to breast cancer in females, explaining why very few investigations have been
      conducted in Iran. Limited coverage in the literature make gender-specific
      findings difficult so future research of this entity involving multi
      institutional cooperation and longer follow up is essential to provide new
      insights about the biological and clinical factors of this rare cancer.

PMID- 24460308
TI  - Transition over 35 years in the incidence rates of primary central nervous system
      tumors in Shanghai, China and histological subtyping based on a single center
      experience spanning 60 years.
AB  - BACKGROUND: Only few epidemiological data on primary central nervous system (CNS)
      tumors in Shanghai have been reported. METHODS: All cases of primary CNS tumors
      that were registered at Center for Disease Control and Prevention (CDC) were
      collected (1973-2007: urban Shanghai; 2003-2007: whole Shanghai city). Trends
      were analyzed using joinpoint analysis and rates were stratified by age, gender
      and region. Histological data were collected from both CDC and Huashan Hospital.
      RESULTS: From 1973 to 2007, the five-year average incidence rate in urban
      Shanghai increased in both genders, especially in the elderly population.
      Joinpoint analysis showed the age-adjusted incidence rate for males increased
      first but then plateaued, whilst rates for females continued increasing over the
      35 years. For the five-year status quo (2003-2007), rural had a higher age-
      adjusted incidence rate than urban populations, and females higher than males,
      especially those with advanced age. According to CDC (2003-2007) and Huashan
      Hospital (1951-2011), the two most common histological subtypes were
      neuroepithelial tumors (with male predominance) and meningiomas (with female
      predominance). CONCLUSIONS: In Shanghai, a steadily increased incidence rate of
      primary CNS tumors was observed in general, and in the elderly and female
      population in particular.

PMID- 24460309
TI  - Long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in
      treatment of nasopharyngeal carcinoma with cervical lymph node metastases.
AB  - OBJECTIVE: The long-term efficacy of microwave hyperthermia combined with
      chemoradiotherapy in treating nasopharyngeal carcinoma (NPC) with metastatic foci
      in cervical lymph nodes was evaluated. METHODS: A total of 154 cases of N2 or N3
      stage NPC were randomized into two groups: hyperthermia group (76 cases) and
      control group (78 cases). Both received cisplatin chemotherapy and radiotherapy.
      In addition, the hyperthermia group further received microwave hyperthermia to
      the metastatic cervical nodes with different patterns (before or after
      radiotherapy), heating temperatures (T90 < 43 degrees  and T90 >= 43 degrees )
      and hyperthermia episodes (< 4 times, 4-10 times and > 10 times). RESULTS: The 3
      month and 5-year complete response (CR) rates of cervical lymph nodes in the
      hyperthermia group were significantly higher than those in the control group. The
      5-year disease-free survival (DFS) rate and the 3-year / 5-year overall survival
      rate in the hyperthermia group were also significantly higher. There was no
      significant difference in 5-year metastatic rates. In the hyperthermia group, the
      3-month and 5-year CR rates of T90 < 43 degrees  treatment were significantly
      lower than with T90 >= 43 degrees  treatment. The CR rate was highest when the
      hyperthermia was performed 4-10 times. There were no significant differences in 3
      month and 5-year CR rates between hyperthermia before or after radiotherapy
      treatment. CONCLUSION: Microwave hyperthermia combined with chemoradiotherapy can
      increase local control, DFS and 3, 5-year overall survival rates of patients with
      N2 ~ N3 stage NPC. The heating temperature should be over 43 degrees  with
      hyperthermia repeated 4-10 times.

PMID- 24460310
TI  - Survival outcomes after whole brain radiation therapy and/or stereotactic
      radiosurgery for cancer patients with metastatic brain tumors in Korea: a
      systematic review.
AB  - AIM: To compare survival outcomes after whole brain radiation therapy (WBRT),
      stereotactic radiosurgery (SRS), and WBRT plus SRS combination therapy in Korea,
      by performing a quantitative systematic review. MATERIALS AND METHODS: We
      searched 10 electronic databases for reports on Korean patients treated with WBRT
      or SRS for brain metastases published prior to July 2010. Independent reviewers
      screened all articles and extracted the data. When a Kaplan-Meier survival curve
      was available, median survival time and standard errors were calculated. Summary
      estimates for the outcomes in each study were calculated using the inverse
      variance random-effects method. RESULTS: Among a total of 2,761 studies, 20
      studies with Korean patients (n=1,053) were identified. A combination of 12
      studies (n=566) with WBRT outcomes showed a median survival time of 6.0 months
      (95%CI: 5.9-6.2), an overall survival rate of 5.6% (95%CI: 1-24), and a 6-month
      survival rate of 46.5% (95%CI: 37.2-56.1). For nine studies (n=412) on SRS, the
      median survival was 7.9 months (95%CI: 5.1-10.8), and the 6-month survival rate
      was 63.1% (95%CI: 49.8-74.8). In six studies (n=75) using WBRT plus SRS, the
      median survival was 10.7 months (95%CI: 4.7-16.6), and the overall and 6-month
      survival rates were 16.8% (95%CI: 6.2-38.2) and 85.7% (95%CI: 28.3-96.9),
      respectively. CONCLUSIONS: WBRT plus SRS showed better 1-year survival outcome
      than of WBRT alone for Korean patients with metastatic brain tumors. However, the
      results of this analysis have to be interpreted cautiously, because the risk
      factors of patients were not adjusted in the included studies.

PMID- 24460311
TI  - Reasons for patient's delay in diagnosis of breast carcinoma in Pakistan.
AB  - BACKGROUND: Delay in diagnosis of breast cancer is associated with a poorer
      survival and a pivotal contribution to this delayed diagnosis comes from patient
      delay in presenting at a clinic. Reasons involved must be evaluated in order to
      decrease this reducible delay. OBJECTIVES: i) To evaluate the reasons for patient
      delay in diagnosis of breast cancer; ii) to investigate any association with
      other variables. MATERIALS AND METHODS: A 6 month cross sectional study (from
      July 2012 to Dec 2012), was carried out in Surgical and Oncology Units of Civil
      Hospital, Karachi. A total of 100 females diagnosed with breast cancer of any
      histological type were interviewed after informed consent and relevant data were
      collected. Due ethical clearance was obtained. RESULTS: Mean age was 47.5+/-12.1
      years with a range from 25-77 years. Mean duration of delay was 5.13+/-4.8
      months, from shortest 1 month to longest 36 months. Duration of delay was
      observed to be no delay (<1 month) in 28%, short delay (1-3 months) in 30% and
      long delay (>3 months) in 42% of patients. Considering the symptoms as "harmless"
      (39%) was the most frequent reason of delay followed by "temporary" (20%) and the
      "use of traditional methods" (12%). Most common reason for later approaches was
      an increase in the size of the lump (41%). Statistically significant association
      (p-value <0.05) of longer patient delay was obtained with being single, being
      illiterate, painless breast lump as the first symptom, negative family history of
      breast cancer and vague attribution of the symptoms. CONCLUSIONS: Significant
      delay in approach to health care facility was observed in our study due to
      variable reasons given by women. Sufficient awareness regarding breast cancer,
      its symptoms and favorable effects of a timely diagnosis on prognosis must be
      imparted to our general population.

PMID- 24460312
TI  - T-SPOT.TB for detection of tuberculosis infection among hematological malignancy
      patients and hematopoietic stem cell transplant recipients.
AB  - The diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is
      recommended in hematological malignancy patients and before hematopoietic stem
      cell transplantation (Guidelines for the prevention and management of infectious
      complications of solid organ transplantation, 2004). Compared to traditional
      methods such as tuberculin skin test (TST), T-SPOT.TB has been shown to be more
      specific. In the present study we enrolled 536 patients for whom T-SPOT.TB was
      performed, among which 295 patients also received the TST test. The agreement
      (79%) between T-SPOT.TB and TST was poor (?=0.274, P<0.001). The patients with
      positive T-SPOT.TB results numbered 62 (11.6%), in which only 20 (48.8%) of the
      41 receiving the TST test had positive results. A majority of the patients with T
      SPOT.TB positive results had some other evidence ofTB, such as TB history,
      clinical symptoms and an abnormal chest CT scan. Active TB was found in 9
      patients, in which 2 had negative TST results. We followed up the patients and no
      one developed active TB. Our study suggested that the T-SPOT.TB may be more
      useful for screening LTBI and active TB in hematological malignancy patients and
      hematopoietic stem cell transplant recipients than the TST test. 

PMID- 24460313
TI  - Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal
      cancer cases.
AB  - BACKGROUND: Colorectal cancer is the fourth most common cancer worldwide and the
      second leading cause of cancer-related death. FOLFOX is the most common regimen
      used in the first-line chemotherapy in advanced colorectal cancer, but only half
      of the patients respond to this regimen and we have almost no clue in predicting
      resistance in such first-line application. METHODS: To explore the potential
      molecular biomarkers predicting the resistance of FOLFOX regimen as the first
      line treatment in advanced colorectal cancer, we screened microRNAs in serum
      samples from drug-responsive and drug-resistant patients by microarrays. Then
      differential microRNA expression was further validated in an independent
      population by reverse transcription and quantitative real- time PCR. RESULTS: 62
      microRNAs expressing differentially with fold-change >2 were screened out by
      microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144)
      were chosen for further validation in an independent population (N=72). Our
      results indicated serum miR-19a to be significantly up-regulated in resistance
      phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of
      serum miR-19a to discriminate the resistant patients from the response ones was
      66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally
      observed serum miR-19a had a complementary value for cancer embryonic antigen
      (CEA). Stratified analysis further revealed that serum miR-19a predicted both
      intrinsic and acquired drug resistance. CONCLUSIONS: Our findings confirmed
      aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients,
      suggesting serum miR-19a could be a potential molecular biomarker for predicting
      and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced
      colorectal cancer patients.

PMID- 24460314
TI  - Pretreatment effects of regular aerobic training on the IGF system and
      hepatotoxicity induced by doxorubicin in rats.
AB  - AIMS: To examine the pretreatment effects of regular aerobic training on the IGF
      system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity
      in rats. MATERIALS AND METHODS: Forty-eight male rats were divided into
      groups:(1) control+placebo (2)control+DOX10 mg.kg-1 (3)control+DOX20 mg.kg-1 (4)
      training+placebo (5) training+DOX10 mg.kg-1 (6) training+DOX20 mg.kg-1.
      Hepatotoxicity was induced by DOX with dosages of 10 and 20 mg.kg-1. The rats in
      groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5
      days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and
      4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline
      solution, DOX10 mg.kg-1 and DOX20 mg.kg-1, respectively. RESULTS: Administration
      of DOX20 mg.kg-1 caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an
      insignificant decrease in IGFBP-3, as compared to the control+placebo group.
      However, after six weeks of aerobic training and DOX treatment with 10mg.kg-1 and
      or/ 20mg.kg-1 an insignificant decrease in IGF-1, an insignificant increase in
      IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison
      to C+DOX10 and C+DOX20. CONCLUSIONS: Hepatotoxicity of doxorubicin is dose
      dependent and pretreatment with regular aerobic training may improve DOX-induced
      hepatotoxicity by up-regulation of IGFBP3.

PMID- 24460315
TI  - EA-D p45-IgG as a potential biomarker for nasopharyngeal carcinoma diagnosis.
AB  - AIM: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot
      test kit. METHODS: Serum samples from 64 NPC patients and healthy subjects with
      four specific VCA-IgA/EA-IgA profiles were tested with an anti-EBV Western blot
      test kit from EUROIMMUN AG. Proteins were quantified with scores of intensity
      visually assigned to the protein bands. The markers which showed statistical
      differences between the NPC and non-NPC subjects were further evaluated in
      another 32 NPC patients and 32 controls in comparison with established biomarkers
      including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA. RESULTS: Among
      the markers screened, EA-D p45-IgG showed a statistically significant difference
      (p < 0.05) between NPC and non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA
      positive NPC patients and 32 control subjects, the diagnostic accuracy of EA-D
      p45-IgG was 78.1% with a positive predictive value of 77.8% and a negative
      predictive value of 78.6%. In the verification experiment, the specificity and
      sensitivity of EA-D p45-IgG were 75.0% and 90.6 %, respectively. CONCLUSIONS: EA
      D p45-IgG might be a potential biomarker for NPC diagnosis, especially among VCA
      IgA positive subjects.

PMID- 24460316
TI  - ATF3 activates Stat3 phosphorylation through inhibition of p53 expression in skin
      cancer cells.
AB  - AIM: ATF3, a member of the ATF/CREB family of transcription factors, has been
      found to be selectively induced by calcineurin/NFAT inhibition and to enhance
      keratinocyte tumor formation, although the precise role of ATF3 in human skin
      cancer and possible mechanisms remain unknown. METHODS: In this study, clinical
      analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was
      accumulated in skin cancer tissues. Functional assays demonstrated that ATF3
      significantly promoted skin cancer cell proliferation. RESULTS: Mechanically,
      ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of
      p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell
      proliferation was dependent on the p53-Stat3 signaling cascade. CONCLUSION:
      Together, the results indicate that ATF3 might promote skin cancer cell
      proliferation and enhance skin keratinocyte tumor development through inhibiting
      p53 expression and then activating Stat3 phosphorylation.

PMID- 24460317
TI  - Risk factors for stage IV breast cancer at the time of presentation in Turkey.
AB  - BACKGROUND: Breast cancer (BC) is the one of the most common cancers in women. It
      is also a leading cause of death. Unfortunately, some patients initially present
      with distant metastases and are diagnosed with stage IV disease that is nearly
      always, by then, incurable. This retrospective analysis investigated the risk
      factors for stage IV BC that may underlie such late presentation. MATERIALS AND
      METHODS: In all, 916 patients with BC who visited the medical oncology polyclinic
      of eight different centres in Turkeybetween December 2011 and January 2013 were
      analysed. RESULTS: A total of 115 patients (12.6%) presented with stage IV
      disease. In univariate analysis; to comparing these with patients at other
      stages, no statistical difference was found for median diagnosis age or age at
      menarche (p=0.611 and p=0.820), whereas age at menopause and age at first live
      birth were significant (p=0.018 and p=0.003). No difference was detected in terms
      of accompanying diseases, use of oral contraceptives and hormone replacement
      therapy, smoking, alcohol consumption and the rate of family history of BC
      between the patients (p=0.655, p=0.389, p=0.762, p=0.813, p=0.229, p=0.737).
      However, screening methods were employed less often, the rate of illiteracy was
      higher, and the rate of other cancers was higher in patients with stage IV BC
      (p=0.022, p=0.022, p=0.018). No statistical difference was observed between the
      patients in terms of tumour histopathology, and status of oestrogen receptor,
      progesterone receptor, or human epidermal growth factor-2 receptor (p=0.389,
      p=0.326, p=0.949, p=0.326). Grade 3 tumours were more frequent in patients with
      stage IV disease (p<0.001). On multivariate analysis, risk factors for stage IV
      breast cancer at the time of presentation were found to be age at first live
      birth and educational level (p=0.003 and p=0.047). CONCLUSIONS: Efforts should be
      made to perform mammography scans, in particular, at regular intervals through
      national training programs for all women, particularly those with family
      histories of breast and other types of cancer, and to establish early diagnosis
      of BC long before it proceeds to stage IV. Additionally, women's education had
      better be upgraded. In order to make women aware of BC, national education
      programmes must be organised.

PMID- 24460318
TI  - Capability for change at community health centers serving Asian Pacific
      Islanders: an exploratory study of a cancer screening evidence-based
      intervention.
AB  - BACKGROUND: Understanding and enhancing change capabilities, including Practice
      Adaptive Reserve (PAR), of Community Health Centers (CHCs) may mitigate cancer
      related health disparities. MATERIALS AND METHODS: Using stratified random
      sampling, we recruited 232 staff from seven CHCs serving Asian Pacific Islander
      communities to complete a self-administered survey. We performed multilevel
      regression analyses to examine PAR composite scores by CHC, position type, and
      number of years worked at their clinic. RESULTS: The mean PAR score was 0.7 (s.d.
      0.14). Higher scores were associated with a greater perceived likelihood that
      clinic staff would participate in an evidence-based intervention (EBI).
      Constructs such as communication, clinic flow, sensemaking, change valence, and
      resource availability were positively associated with EBI implementation or
      trended toward significance. CONCLUSIONS: PAR scores are positively associated
      with perceived likelihood of clinic staff participation in cancer screening EBI.
      Future research is needed to determine PAR levels most conducive to implementing
      change and to developing interventions that enhance Adaptive Reserve.

PMID- 24460319
TI  - Implementing a cervical cancer awareness program in low- income settings in
      Western China: a community-based locally affordable intervention for risk
      reduction.
AB  - BACKGROUND: Some 60 years after introduction of the Papanicolaou smear worldwide,
      cervical cancer remains a burden in developing countries where >85% of world new
      cases and deaths occur, suggesting a failure to establish comprehensive cervical
      cancer control programs. Effective interventions are available to control
      cervical cancer but are not all affordable in low-income settings. Disease
      awareness saves lives by risk-reduction as witnessed in reducing mortality of
      HIV/AIDS and smoking-related cancers. SUBJECTS AND METHODS: We initiated a
      community-based awareness program on cervical cancer in two low-income Muslim
      Uyghur townships in Kashi (Kashgar) Prefecture, Xinjiang, China in 2008. The
      education involved more than 5,000 women from two rural townships and awareness
      was then evaluated in 2010 and 2011, respectively, using a questionnaire with 10
      basic knowledge questions on cervical cancer. Demographic information was also
      collected and included in an EpiData database. A 10-point scoring system was used
      to score the awareness. RESULTS: The effectiveness and feasibility of the program
      were evaluated among 4,475 women aged 19-70 years, of whom >92% lived on/ below
      US$1.00/day. Women without prior education showed a poor average awareness rate
      of 6.4% (164/2,559). A onetime education intervention, however, sharply raised
      the awareness rate by 4-fold to 25.5% (493/1,916). Importantly, low income and
      illiteracy were two reliable factors affecting awareness before or after
      education intervention. CONCLUSIONS: Education intervention can significantly
      raise the awareness of cervical cancer in low-income women. Economic development
      and compulsory education are two important solutions in raising general disease
      awareness. We propose that implementing community-based awareness programs
      against cervical cancer is realistic, locally affordable and sustainable in low
      income countries, which may save many lives over time and, importantly, will
      facilitate the integration of comprehensive programs when feasible. In this
      context, adopting this strategy may provide one good example of how to achieve
      "good health at low cost".

PMID- 24460321
TI  - Computational analysis of the 3-D structure of human GPR87 protein: implications
      for structure-based drug design.
AB  - The G-protein coupled receptor 87 (GPR87) is a recently discovered orphan GPCR
      which means that the search of their endogenous ligands has been a novel
      challenge. GPR87 has been shown to be overexpressed in squamous cell carcinomas
      (SCCs) or adenocarcinomas in lungs and bladder. The 3D structure of GPR87 was
      here modeled using two templates (2VT4 and 2ZIY) by a threading method.
      Functional assignment of GPR87 by SVM revealed that along with transporter
      activity, various novel functions were predicted. The 3D structure was further
      validated by comparison with structural features of the templates through Verify
      3D, ProSA and ERRAT for determining correct stereochemical parameters. The
      resulting model was evaluated by Ramachandran plot and good 3D structure
      compatibility was evidenced by DOPE score. Molecular dynamics simulation and
      solvation of protein were studied through explicit spherical boundaries with a
      harmonic restraint membrane water system. A DRY-motif (Asp-Arg-Tyr sequence) was
      found at the end of transmembrane helix3, where GPCR binds and thus activation of
      signals is transduced. In a search for better inhibitors of GPR87, in silico
      modification of some substrate ligands was carried out to form polar interactions
      with Arg115 and Lys296. Thus, this study provides early insights into the
      structure of a major drug target for SCCs. 

PMID- 24460320
TI  - IL-6-6331 (T/C, rs10499563) is associated with decreased risk of gastric cancer
      in Northern Chinese.
AB  - BACKGROUND: Polymorphisms of genes encoding cytokines could be potential
      biomarkers to predict risk of gastric cancer (GC). Here, we investigated the
      association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter
      region and GC risk. METHODS: In this case-control study of 215 GC cases and 518
      non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped
      by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: Individuals with the TC or CC genotype were associated with a
      significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049)
      compared with TT wild-type carriers. Ther C allele was also associated with
      significantly decreased risk of GC (OR=0.715, 95%CI: 0.536- 0.954, P=0.023)
      compared with the T allele. In the stratification analysis, TC or CC genotypes
      were associated with significantly decreased GC risk in subgroups of males,
      people older than 60, and H. pylori-positive cases. However, no significant
      interaction was observed for TC or CC genotypes with H. pylori infection. On
      stratification with the Lauren classification, TC or CC genotypes were associated
      with significantly decreased risk of diffuse- type GC (OR=0.497, 95%CI: 0.266
      0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori
      positive cases. CONCLUSIONS: The IL-6 -6331 (T/C, rs10499563) polymorphism is
      associated with genetic susceptibility of GC and may have the potential to
      predict GC risk.

PMID- 24460322
TI  - Human Papillomavirus (HPV) infection in women participating in cervical cancer
      screening from 2006 to 2010 in Shenzhen City, South China.
AB  - PURPOSE: Human papillomavirus (HPV) infection plays an important role in the
      development of cervical cancer, but the prevalence of HPV infection in women of
      Shenzhen city remains unclear. The present study was performed to describe the
      change of cervical HPV infection in females who participated in voluntary
      cervical cancer screening from 2006 to 2010 in Shenzhen city, China. METHODS: A
      total of 4, 413 women were recruited. HPV infections were genotyped by polymerase
      chain reaction (PCR) and reversed dot blot hybridization in Shenzhen Maternity
      and Child Health Hospital. RESULTS: The prevalence of HPV infection was 13.8%.
      The five most commonly found HPV types were HPV16 (3.47%), HPV58 (1.68%), HPV33
      (1.38%), HPV43 (1.36%) and HPV18 (1.27%). The secular trends of major HPV type
      specific were diverse. Among of them, the prevalence of HPV18 increased sharply
      while others increased slowly or even decreased in the period. The change of
      total HPV, single HPV and multiple HPV infection were similar during the five
      years. CONCLUSIONS: Our findings suggested that HPV infection is common with
      HPV16 and HPV 58 as the primary subtypes in women in Shenzhen city. The
      prevalence of HPV 18 infection is increasing faster than any others, which will
      lead it to be one of the main subtypes in this city in the future.

PMID- 24460323
TI  - Enhancement of anti-tumor activity of Newcastle disease virus by the synergistic
      effect of cytosine deaminase.
AB  - This study was conducted to investigate enhancement of anti-tumor effects of the
      lentogenic Newcastle disease virus Clone30 strain (NDV rClone30) expressing
      cytosine deaminase (CD) gene against tumor cells and in murine groin tumor
      bearing models. Cytotoxic effects of the rClone30-CD/5-FC on the HepG2 cell line
      were examined by an MTT method. Anti-tumor activity of rClone30-CD/5-FC was
      examined in H22 tumor-bearing mice. Compared to the rClone30-CD virus treatment
      alone, NDV rClone30-CD/5-FC at 0.1 and 1 MOIs exerted significant cytotoxic
      effects (P<0.05) on HepG2 cells. For treatment of H22 tumor-bearing mice,
      recombinant NDV was injected together with 5-FC given by either intra-tumor
      injection or tail vein injection. When 5-FC was administered by intra-tumor
      injection, survival for the rClone30-CD/5-FC-treated mice was 4/6 for 80 days
      period vs 1/6 , 0/6 and 0/6 for the mice treated with rClone30-CD, 5-FC and
      saline alone, respectively. When 5-FC was given by tail vein injection, survival
      for the rClone30-CD/5-FC-treated mice was 3/6 vs 2/6 , 0/6 and 0/6 for the mice
      treated with rClone30-CD, 5-FC or saline alone, respectively. In this study, NDV
      was used for the first time to deliver the suicide gene for cancer therapy.
      Incorporation of the CD gene in the lentogenic NDV genome together with 5-FC
      significantly enhances cell death of HepG2 tumor cells in vitro, decreases tumor
      volume and increases survival of H22 tumor-bearing mice in vivo. 

PMID- 24460324
TI  - Clinical prognostic factors and survival outcome in renal cell carcinoma patients
      -a malaysian single centre perspective.
AB  - BACKGROUND: This study concerns clinical characteristics and survival of renal
      cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well
      as the prognostic significance of presenting symptoms. MATERIALS AND METHODS: The
      clinical characteristics, presenting symptoms and survival of RCC patients
      (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were
      macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of
      weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and
      multivariate Cox regression analyses were performed to determine the prognostic
      significance of these presenting symptoms. Kaplan Meier and log rank tests were
      employed for survival analysis. RESULTS: The 2002 TNM staging was a prognostic
      factor (p<0.001) but Fuhrman grading was not significantly correlated with
      survival (p=0.088). At presentation, 76.8% of the patients were symptomatic.
      Generally, symptomatic tumours had a worse survival prognosis compared to
      asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease
      specific survival except frank haematuria and loin pain on univariate Cox
      regression analysis. On multivariate analysis adjusted for stage, only clinically
      palpable abdominal mass remained statistically significant (p=0.027). The mean
      tumour size of palpable abdominal masses, 9.5+/-4.3cm, was larger than non
      palpable masses, 5.3+/-2.7cm (p<0.001). CONCLUSIONS: This is the first report
      which includes survival information of RCC patients from Malaysia. Here the TNM
      stage and a palpable abdominal mass were independent predictors for survival.
      Further investigations using a multicentre cohort to analyse mortality and
      survival rates may aid in improving management of these patients.

PMID- 24460325
TI  - Selective miRNA expression profile in chronic myeloid leukemia K562 cell-derived
      exosomes.
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of
      hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an
      oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1
      kinase is a treatment of choice for control of CML. OBJECTIVE: Recent studies
      have demonstrated that miRNAs within exosomes from cancer cells play crucial
      roles in initiation and progression. This study was performed to assess miRNAs
      within exosomes of K562 cells. METHODS: miRNA microarray analysis of K562 cells
      and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM
      LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) analyses were also carried out. GO terms and signaling pathways were
      categorized into 66 classes (including homophilic cell adhesion, negative
      regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such
      as Wnt). RESULTS: In exosomes, 49 miRNAs were up regulated as compared to K562
      cells, and two of them were further confirmed by quantitative real-time PCR.
      There are differentially expressed miRNAs between K562 cell derived-exosomes and
      K562 cells. CONCLUSION: Selectively expressed miRNAs in exosomes may promote the
      development of CML via effects on interactions (e.g. adhesion) of CML cells with
      their microenvironment.

PMID- 24460326
TI  - Sleep duration and cancer risk: a systematic review and meta-analysis of
      prospective studies.
AB  - To assess the risk of cancers associated with sleep duration using a meta
      analysis of published cohort studies, we performed a comprehensive search using
      PubMed, Embase and Web of Science through October 2013. We combined hazard ratios
      (HRs) from individual studies using meta-analysis approaches. A random effect
      dose-response analysis was used to evaluate the relationship between sleep
      duration and cancer risk. Subgroup analyses and sensitivity analyses were also
      performed. Publication bias was evaluated using Funnel plots and Begg's test. A
      total of 13 cohorts from 12 studies were included in this meta-analysis, which
      included 723,337 participants with 15,156 reported cancer outcomes during a
      follow-up period ranging from 7.5 to 22 years. The pooled adjusted HRs were 1.06
      (95% CI: 0.92, 1.23; P for heterogeneity=0.003) for short sleep duration, 0.91
      (95% CI: 0.78, 1.07; P for heterogeneity <0.0001) for long sleep duration. In
      subgroup analyses stratified by cancer type, long duration of sleep showed an
      inverse relation with hormone-related cancer (HR=0.79; 95% CI: 0.65, 0.97; P for
      heterogeneity=0.009) and a greater risk of colorectal cancer (HR=1.29; 95% CI:
      1.09, 1.52; P for heterogeneity=0.346). Further meta-analysis on dose-response
      relationships showed that the relative risks of cancer were 1.00 (95% CI: 0.99,
      1.01; P for linear trend=0.9151) for one hour of sleep increment per day, and
      1.00 (95% CI: 0.98, 1.01; P for linear trend=0.7749) for one hour of sleep
      increment per night. No significant dose-response relationship between sleep
      duration and cancer was found on non-linearity testing (P=0.5053). Our meta
      analysis suggests a positive association between long sleep duration and
      colorectal cancer, and an inverse association with incidence of hormone related
      cancers like those in the breast. Studies with larger sample size, longer follow
      up times, more cancer types and detailed measure of sleep duration are warranted
      to confirm these results. 

PMID- 24460327
TI  - Cancer incidence in southwest of iran: first report from khuzestan population
      based cancer registry, 2002-2009.
AB  - BACKGROUND: Cancer incidence rates are increasing particularly in developing
      countries. It is crucial for policy makers to know basic cancer epidemiology in
      each region to design comprehensive prevention plans. There have hitherto been no
      population-based data available for cancer in Khuzestan province. The present
      report is a first from the regional population-based cancer registry for the
      period of 2002-2009. MATERIALS AND METHODS: Data were collected retrospectively
      reviewing all new cancer patients whom were registered in Khuzestan province
      cancer registry during an 8-year period (2002-2009). All cases were coded based
      on the ICD-O-3 coding system and collected data were computerized using SPSS
      (Chicago, IL) software, version 11.5. The age standardized incidence rates (ASRs)
      per 100,000 person-year for all cancers were computed using the indirect method
      of standardization to the world population. RESULTS: During the 8-year study
      period, 16,801 new cancer cases were registered. Based on the computed ASRs, the
      five most frequent malignancies in females were breast (26.4 per 100,000), skin
      (13.6), colorectal (5.72), stomach (4.31) and bladder(4.07) and in males, the
      five most frequent were skin (16.0 per 100,000), bladder (10.7),prostate (7.64),
      stomach (7.17), and colorectal (6.32).The ASR for all malignancies in women was
      92.5 per 100,000, and that for men was 87.4. CONCLUSIONS: The observed patterns
      from the analysis of Khuzestan cancer registry data will lead to better
      understanding of the epidemiology of various malignancies in this part ofthe
      country and consequently provide a useful guide for authorities to make
      efficacious decisions and policies about a cancer control program for south-west
      Iran.

PMID- 24460328
TI  - A novel approach to cloning and expression of human thymidylate synthase.
AB  - Thymidylate synthase (TS) catalyzes the transfer of a methyl group from
      methylenetetrahydrofolate to dUMP to form dTMP. It is a primary target in the
      chemotherapy of colorectal cancers and some other neoplasms. In order to obtain
      pure protein for analysis of structure and biological function, an expression
      vector TS-pET28b (+) was constructed by inserting wild-type human thymidylate
      synthase (hTS) cDNA into pET28b (+). Then an expression strain was selected after
      transformation of the recombined plasmid into Rosetta (DE3). Fusion protein with
      His-tag was efficiently expressed in the form of inclusion bodies after IPTG
      induction and the content was approximately 40.0% of total bacteria proteins
      after optimizing expression conditions. When inclusion bodies were washed,
      dissolved and purified by Ni-NTA under denatured conditions, the purity was up to
      90%. On SDS-PAGE and West-blotting, the protein band was found to match well with
      the predicted relative molecular mass-36kDa. Bioactivity was 0.1 U/mg. The
      results indicated that high-level expression of wild-type hTS cDNA can be
      achieved in prokaryotes with our novel method, facilitating research into related
      chemotherapy. 

PMID- 24460329
TI  - MiR-21 upregulation induced by promoter zone histone acetylation is associated
      with chemoresistance to gemcitabine and enhanced malignancy of pancreatic cancer
      cells.
AB  - BACKGROUND AND AIMS: MicroRNA-21 (miR-21) is reported to be overexpressed and to
      contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic
      ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation
      of miR-21 expression by epigenetic change and its impact on chemoresistance and
      malignant properties of of pancreatic cancer. MATERIALS AND METHODS: We
      retrospectively collected 41 cases of advanced pancreatic cancer patients who
      were sensitive or resistant to gemcitabine and assessed levels of serum
      circulating miR-21 for correlation with cytotoxic activity. Histone acetylation
      in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine
      resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were
      transfected with pre-miR-21 precursors (pre-miR-21) and antisense
      oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and
      metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT
      level was evaluated in these cells. RESULTS: Serum miR-21 levels were increased
      in gemcitabine- resistant PDAC patients compared with gemcitabine-sensitive
      subjects. The miR-21 levels were increased in 6 PDAC cells treated with
      gemcitabine significantly, associated with 50% inhibitory concentrations (IC50s).
      Histone acetylation levels at miR-21 promoter were increased in PDAC cells after
      treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21
      expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine
      resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further
      increased invasion and metastasis ability, decreased PTEN, and elevated pAKT
      levels in these two lines. In contrast, anti-miR-21 transfection could reverse
      invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine.
      CONCLUSIONS: MiR-21 upregulation induced by histone acetylation in the promoter
      zone is associated with chemoresistance to gemcitabine and enhanced malignant
      potential in pancreatic cancer cells.

PMID- 24460330
TI  - Terpinen-4-ol induces autophagic and apoptotic cell death in human leukemic HL-60
      cells.
AB  - BACKGROUND: Terpinen-4-ol, a monoterpene, is found as the main component of
      essential oil extracts from many plants. In this study apoptotic and autophagic
      types of cell death induced by terpinen-4-ol and associated mechanisms were
      investigated in human leukemic HL-60 cells. MATERIALS AND METHODS: The
      cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay.
      Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were
      determined by Western blotting. Cell morphology was examined under a transmission
      electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by
      immunoblotting. RESULTS: Terpinen-4-ol exhibited cytotoxicity to human leukemic
      HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells
      was due to induction of cytochrome c release from mitochondria and cleavage of
      Bid protein after the stimulation of caspase-8. There was a slightly decrease of
      Bcl-xl protein level. The characteristic cell morphology of autophagic cell death
      was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular
      level, the results from Western blot analysis showed that terpinen-4-ol
      significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory
      proteins required for autophagy in mammalian cells. CONCLUSIONS: Terpinen-4-ol
      induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.

PMID- 24460331
TI  - Tea consumption, alcohol drinking and physical activity associations with breast
      cancer risk among Chinese females: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate associations between tea consumption, alcohol drinking and
      physical activity and breast cancer risk among Chinese females. METHODS: Three
      English databases (PubMed, ScienceDirect and Wiley) and three Chinese databases
      (CNKI, WanFang and VIP) were independently searched by 2 reviewers up to December
      2012, complemented by manual searches. The quality of included studies was
      assessed with the Newcastle-Ottawa Scale items. Random-effects models were used
      to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs).
      Potential publication bias was estimated through Egger's and Begg's tests.
      Heterogeneity between studies was evaluated with I2 statistics. RESULTS: Thirty
      nine studies involving 13,204 breast cancer cases and 87,248 controls were
      identified. Compared with non-drinkers, regular tea drinkers had decreased risk
      (OR=0.79, 95%CIs: 0.65-0.95; I2=84.9%; N=16). An inverse association was also
      found between regular physical activity and breast cancer risk (OR=0.73, 95%CIs:
      0.63-0.85; I2=77.3%; N=15). However, there was no significant association between
      alcohol drinking and breast cancer risk (OR=0.85, 95%CIs: 0.72- 1.02; I2=63.8%;
      N=26). Most of the results from the subgroup analysis were consistent with the
      main results. CONCLUSION: Tea consumption and physical activity are significantly
      associated with a decreased risk of breast cancer in Chinese females. However,
      alcohol drinking may not be associated with any elevation of risk.

PMID- 24460332
TI  - Plasma post-operative miR-21 expression in the prognosis of gastric cancers.
AB  - Tumor-associated microRNAs have been detected in serum or plasma, but whether
      plasma microRNA-21 (miR-21) could be a potential circulating biomarker for
      gastric cancer (GC) prognosis in Chinese is still uncertain. Real-time
      quantitative reverse transcription PCR (qRT-PCR) was employed in this study to
      compare the relative expression of miR-21 between pre-operative and post
      operative paired plasmas from 42 patients with primary GCs. The results showed
      that the expression levels of miR-21 in the post-operative plasmas were
      significantly reduced by an average of 18.2 times in all patients when compared
      to the pre-operative plasmas, and by 22.1 times in the subgroup of patients
      without family history, while only 1.76 times in the subgroup of patients with a
      family history. With respect of clinicopathological characteristics, the plasma
      miR-21 expression was highly associated with differentiation degree and lymph
      node metastasis rate. The results suggested plasma miR-21 could be a novel
      potential biomarker for GC prognosis and evaluation of surgery outcomes,
      especially in patients without a family history. 

PMID- 24460333
TI  - Clinical, cytogenetic and CYP1A1 exon-1 gene mutation analysis of Beedi workers
      in Vellore region, Tamil Nadu.
AB  - BACKGROUND: Beedi rollers are exposed to unburnt tobacco dust through cutaneous
      and pharyngeal route and it is extremely harmful to the body since it is
      carcinogenic in nature and can cause cancer during long exposure. This indicates
      that occupational exposure to tobacco imposes considerable genotoxicity among
      beedi workers. MATERIALS AND METHODS: In the present study, 27 beedi workers and
      age and sex matched controls were enrolled for clinical, cytogenetics and
      molecular analysis. Clinical features were recorded. The workers were in the age
      group of 28-67 years and were workers exposure from 8-60 years. Blood samples
      were collected from workers and control subjects and lymphocyte cultures were
      carried out by using standard technique, slides were prepared and 50 metaphases
      were scored for each sample to find the chromosomal abnormalities. For molecular
      analysis the genomic DNA was extracted from peripheral blood, to screen the
      variations in gene, the exon 1 of CYP1A1 gene was amplified by polymerase chain
      reaction (PCR) and then screened with Single Strand Conformation Polymorphism
      (SSCP) analysis. RESULTS: A statistically significant increase was observed in
      the frequencies of chromosomal aberrations in exposed groups when compared to the
      respective controls and variations observed in Exon 1 of CYP1A1(Cytochrome P450,
      family 1, subfamily A, polypeptide 1) gene. CONCLUSIONS: This study shows that,
      the toxicants present in the beedi that enter into human body causes disturbance
      to normal state and behavior of the chromosomes which results in reshuffling of
      hereditary material causing chromosomal aberrations and genomic variations.

PMID- 24460334
TI  - Synergistic effects of PectaSol-C modified citrus pectin an inhibitor of Galectin
      3 and paclitaxel on apoptosis of human SKOV-3 ovarian cancer cells.
AB  - Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be
      involved in cancer progression but its contribution to epithelial ovarian cancer
      (EOC) remains unclear. The present study sought to determine the role of Gal-3 in
      chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX)
      using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin
      (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41%
      increased cell proliferation, 36% decreased caspase-3 activity and 33.6%
      increased substrate-dependent adhesion in the presence of rhGal-3 compared to the
      control case (p<0.001). Treatment of cells with a non-effective dose of PTX
      (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects
      with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3
      activity. Moreover, there was 39% decrease in substrate-dependent adhesion
      compared to control (p<0.001). These results suggest that inhibition of Gal-3
      could be a useful therapeutic tool for combination therapy of ovarian cancer. 

PMID- 24460335
TI  - Preliminary results of a phase I/II study of simultaneous boost irradiation
      radiotherapy for locally advanced nasopharyngeal carcinoma.
AB  - BACKGROUND: The purpose of this article is to present preliminary results of
      simultaneous boost irradiation radiotherapy for locally advanced nasopharyngeal
      carcinoma (NPC). METHODS: Fifty-eight patients who underwent simultaneous boost
      irradiation radiotherapy for NPC in Cancer Center of Sun Yat-sen University
      between September 2004 and December 2009 were eligible. Acute and late toxicities
      were scored weekly according to the Radiation Therapy Oncology Group (RTOG) acute
      and late radiation morbidity scoring schemes. An especial focus was on evidence
      of post-radiation brain injury. Also quality of life was analysed according to
      the EORTC (European Organisation for Research and Treatment of Cancer)
      recommendations. Discrete variables were compared by ?2 test. The Kaplan-Meier
      method was used to calculate the survival rates and generate survival curves.
      RESULTS: A total of 58 patients with a mean follow-up time of 36 months completed
      clinical trials.Fifty- seven patients (98.3) achieved complete remission in the
      primary sites and cervical lymph nodes, with only one patient (1.7%) showing
      partial remission.The most frequently observed acute toxicities during the
      concurrent chemoradiotherapy were mucositis and leucopenia. Four patients (6.9%)
      had RTOG grade 3 mucositis, whereas four patients (6.9%) had grade 3 leucopenia.
      No patient had grade 4 acute toxicity. Three (5.17%) of the patients exhibited
      injury to the brain on routine MRI examination, with a median observation of 32
      months (range, 25-42months). All of them were RTOG grade 0. The 3-year overall,
      regional-free and distant metastasis-free survival rates were 85%, 94% and 91%,
      respectively. CONCLUSION: Simultaneous boost irradiation radiotherapy is feasible
      in patients with locally advanced nasopharyngeal carcinoma. The results showed
      excellent local control and overall survival, with no significant increase the
      incidence of radiation brain injury or the extent of damage. A larger population
      of patients and a longer follow-up period are needed to evaluate ultimate tumor
      control and late toxicity.

PMID- 24460336
TI  - The Interleukin-18 promoter -607C>A polymorphism contributes to nasopharyngeal
      carcinoma risk: evidence from a meta-analysis including 1,886 subjects.
AB  - The interleukin-18 promoter -607C>A gene polymorphism may be related to
      nasopharyngeal carcinoma (NPC) risk but the results of individual studies remain
      conflicting. A meta-analysis including 1,886 subjects from five individual
      studies was therefore performed to provide a more accurate estimation. Pooled
      odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were
      evaluated by fixed- or random-effects models. A significant relationship between
      interleukin-18 promoter -607C>A gene polymorphism and NPC was found in a dominant
      genetic model (OR: 1.351, 95% CI: 1.089-1.676, P=0.006, Pheterogeneity=0.904), a
      homozygote model (OR: 1.338, 95% CI: 1.023-1.751, P=0.034, Pheterogeneity=0.863),
      and a heterozygote model (OR: 1.357, 95% CI: 1.080-1.704, P=0.009,
      Pheterogeneity=0.824). No significant association was detected in either an
      allelic genetic model (OR: 1.077, 95% CI: 0.960-1.207, 0.207,
      Pheterogeneity=0.844) or a recessive genetic model (OR: 1.093, 95% CI: 0.878
      1.361, P=0.425, Pheterogeneity=0.707). In conclusion, a significant association
      was found between interleukin-18 promoter -607C>A gene polymorphism and NPC risk.
      Individuals with the C allele of interleukin-18 promoter -607C>A gene
      polymorphism have a higher risk of NPC development. 

PMID- 24460337
TI  - The SOCS-1 -1478CA/del polymorphism is not associated with colorectal cancer or
      age at onset in Turkish subjects.
AB  - BACKGROUND: Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of
      many cytokine signaling pathways and its abnormal expression has been identified
      in several human malignancies, suggesting potential roles in carcinogenesis. The
      aim of this study was to investigate any association between the functional SOCS-
      1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in
      a Turkish clinical sample. MATERIALS AND METHODS: A total of 122 subjects were
      enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 
      1478CA>del polymorphism was genotyped using a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The odds
      ratio of the del allele for CC relative to the CA allele was not significantly
      different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did
      not change after adjustment for age and sex on multivariable regression analysis
      (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was
      analyzed among CC patients in relation to the age at disease onset, we found no
      significant differences between subjects with the del/del, CA/del, and CA/CA
      genotypes. CONCLUSIONS: The results of our study did not point towards a major
      role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish
      subjects.

PMID- 24460338
TI  - Trend analysis of gastrointestinal cancer incidences in Guilan province:
      comparing rates over 15 years.
AB  - BACKGROUND: Cancers of gastric and esophagus are the most frequent
      gastrointestinal (GI) tract cancers in Iran. This study aimed to analyze time
      trends of GI tract cancers in Guilan province by gender and age to provide solid
      scientific evidence for cancer prevention and control. MATERIALS AND METHODS: The
      data were obtained from the Guilan Cancer Registry System and Guilan Provincial
      Health Center, over the 15 year period between 1997 and 2011. Crude incidence and
      age standardized (AS)incidence rates were calculated and annual percent change
      was estimated by Joinpoint software for long term trend analysis. RESULTS: During
      the study period, 8,332 cases of GI malignances with a male to female ratio of
      1:1.73 were registered in Guilan province. The AS rates for esophageal, gastric,
      colon and rectal cancers were 5.97, 14.5, 7.59 and 3.58 per 105 respectively.
      While the trend was declining and relatively constant for esophageal and gastric
      cancer, respectively, the incidence trend for colon and rectal cancers was of
      increase over the period of the study. CONCLUSIONS: The results indicated that
      the incidence of GI cancers was relatively low in Guilan province compared to
      neighboring provinces. An effective cancer control program including prevention
      measures, early detection and effective treatment needs to be implemented to
      reduce cancer morbidity and mortality.

PMID- 24460339
TI  - Risk factors for cervical cancer in rural areas of Wuhan China: a matched case
      control study.
AB  - Cervical cancer is a serious public health problem in developing countries. We
      investigated possible risk factors for cervical cancer in rural areas of Wuhan
      China using a matched case-control study with 33 women diagnosed with cervical
      cancer and 132 healthy women selected from the same area as matched controls. A
      questionnaire, which included questions about general demography conditions,
      environmental and genetic factors, the first sexual intercourse, first marriage
      age, age at first pregnancy, pregnancy first child's age, female personal health
      history, social psychological factors, dietary habits, smoking and alcohol status
      and other living habits was presented to all participants. At the same time, HPV
      infection of every participant was examined in laboratory testing. Results showed
      HPV infection (P<0.000, OR=23.4) and pregnancy first child's age (P<0.000,
      OR=13.1) to be risk factors for cervical cancer. Menopause (P=0.003, OR=0.073)
      was a protective factor against cervical cancer. However, there was no indication
      of associations of environmental (drinking water, insecticide, disinfectant)
      genetic (cancer family history), or life-style factors (smoking status, alcohol
      status, physical training, sleep quality), including dietary habits (intake of
      fruit and vegetable, meat, fried food, bean products and pickled food) or social
      psychological factors with cervical cancer. The results suggest that the risk of
      cervical cancer in Chinese rural women may be associated with HPV infection,
      menopause and the pregnancy first child's age. 

PMID- 24460340
TI  - Gambogenic acid induction of apoptosis in a breast cancer cell line.
AB  - BACKGROUND: Gambogenic acid is a major active compound of gamboge which exudes
      from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro
      has been reported in several studies, including an A549 nude mouse model.
      However, the mechanisms of action remain unclear. METHODS: We used nude mouse
      models to detect the effect of gambogenic acid on breast tumors, analyzing
      expression of apoptosis-related proteins in vivo by Western blotting. Effects on
      cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells
      were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase
      3,-8,-9 were also used to detect effects on caspase family members. RESULTS: We
      found that gambogenic acid suppressed breast tumor growth in vivo, in association
      with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as
      decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell
      proliferation and induced cell apoptosis in a concentration-dependent manner.
      CONCLUSION: Our observations suggested that Gambogenic acid suppressed breast
      cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and
      mitochondrial pathways in vivo and in vitro.

PMID- 24460341
TI  - Comparison between visual inspection of cervix and cytology based screening
      procedures in Bangladesh.
AB  - BACKGROUND: Cervical cancer continues to be a major problem in Bangladesh with
      approximately 18,000 new cases annually of which over 10,000 women die from it.
      Visual inspection of the cervix after 3-5% acetic acid (VIA) application is a
      simple and easy to learn method for cervical cancer screening, although cytology
      based screening is more often applied in developed countries where it has
      successfully reduced the prevalence of cervical cancer. OBJECTIVE: To compare the
      efficacy of VIA and cytology-based primary methods for cervical cancer screening
      in Bangladesh. MATERIALS AND METHODS: This hospital based comparative study was
      conducted at the VIA centre and Colposcopy Clinic of Bangabandhu Sheikh Mujib
      Medical University (BSMMU) from October 2008 to October 2010. RESULTS: Among 650
      women, 74 (11.4%) were VIA+ve and 8 (1.2%) had abnormalities in their Pap smear
      reports. During colposcopy, 38 (7.7%) women had different grades of CIN and 4
      (0.6%) had cervical cancer. The gold standard histology findings proved 20 women
      had CIN I, 14 had CIN II/II and 4 had cervical cancer. Among the 38 histology
      diagnosed abnormalities, VIA test could identify 30 abnormalities including two
      cervical cancers. However, Pap smear could detect only 8 cases of histological
      abnormalities (2 low grade and 6 had high grade lesion) and it missed all the
      cervical cancer cases. The sensitivity and specificity of VIA were 88.9% and
      52.1%. The positive predictive value (PPV) and negative predictive value (NPV)
      were 41.0%, and 92.6% respectively. Moreover, the sensitivity, specificity, PPV
      and NPV of Pap smear were 33.3%, 95.8%, 75.0% and 79.3%, respectively.
      CONCLUSIONS: VIA test should be used as the primary screening tool even with its
      low sensitivity and specificity in low resource countries like Bangladesh. False
      positive results may be greater, but overtreatment can be minimized by colposcopy
      evaluation of the VIA positive women.

PMID- 24460342
TI  - Helicobacter pylori Infection and the risk of colorectal adenoma and
      adenocarcinoma: an updated meta-analysis of different testing methods.
AB  - BACKGROUND AND AIMS: Helicobacter pylori infection may be associated with an
      increased risk of colorectal carcinoma. However, as most studies on this subject
      were relatively small in size and differed at least partially in their designs,
      their results remain controversial. In this study, we aimed to carry out a meta
      analysis to evaluate the potential association of H. pylori infection with
      colorectal adenoma and adenocarcinoma risk, covering all of the different testing
      methods. METHODS: We conducted a search in PubMed, Medline, EBSCO, High Wire
      Press, OVID, and EMBASE covering all published papers up to March 2013. According
      to the established inclusion criteria, essential data were then extracted from
      the included studies and further analyzed by a systematic meta-analysis. Odds
      ratios were employed to evaluate the relationship between H. pylori infection and
      the risk of colorectal neoplasms. RESULTS: Twenty-two studies were included, and
      the odds ratio for the association between H. pylori infection and colorectal
      cancer was 1.49 (95% confidence interval 1.30-1.72). No statistically significant
      heterogeneity was observed. Publication bias was ruled out. CONCLUSION: The
      pooled data suggest H. pylori infection indeed increases the risk of colorectal
      adenoma and adenocarcinoma.

PMID- 24460343
TI  - Detection of HER2 status in breast cancer: comparison of current methods with
      MLPA and real-time RT-PCR.
AB  - Human epidermal growth factor receptor (HER) status is an important prognostic
      factor in breast cancer. There is no globally accepted method for determining its
      status, and which method is most precise is still a matter of debate. We here
      analyzed HER2 mRNA expression by quantitative reverse transcription-PCR (qRT-PCR)
      and HER2 DNA amplification using multiplex ligation-dependent probe amplification
      (MLPA). In parallel, we performed a routine evaluation of HER2 protein by
      immunohistochemistry (IHC). To assess the accuracy of the RT-PCR and MLPA
      techniques, a combination of IHC and fluorescence in situ hybridization (FISH)
      was used, substituting FISH when the results of IHC were ambiguous (2+) and for
      those IHC results that disagreed with MLPA and qRT-PCR, this approach being
      termed IHC-FISH. The IHC results for four samples were not compatible with the
      MLPA and qRT-PCR results; the MLPA and qRT-PCR results for these samples were
      confirmed by FISH. The correlations between IHC-FISH and qRT-PCR or MLPA were
      0.945 and 0.973, respectively. The ASCO/CAP guideline IHC/FISH correlation with
      MLPA was (0.827) and with RT-PCR was (0.854). The correlations between the IHC
      results (0, 1+ as negative, and 3+ as positive) and qRT-PCR and MLPA techniques
      were 0.743 and 0.831, respectively. Given the shortcomings of IHC analysis and
      greater correlations between MLPA, qRT-PCR, and FISH methods than IHC analysis
      alone with each of these three methods, we propose that MLPA and real-time PCR
      are good alternatives to IHC. However a suitable cut-off point for qRT- PCR is a
      prerequisite for determining the exact status of HER2. 

PMID- 24460344
TI  - Association of the Cylin D1 G870A polymorphism with laryngeal cancer: are they
      really related?
AB  - BACKGROUND: Cylin D1(CCDN1) is an important regulator of the cell cycle whose
      alterations are thought to be involved in cancer development. There have been
      many studies indicating CCDN1 amplification or over- expression in a variety of
      cancer types. In addition to gene amplification, the G870A polymorphism may be
      related with altered CCDN1 activity, and therefore with cancer development. This
      hypothesis has been tested in different cancer types but results have been
      contradictory. We therefore aimed to investigate any relationship between CCDN1
      A870G genotypes and laryngeal squamous cell cancer development and progression.
      MATERIALS AND METHODS: A total of 68 Turkish patients with primary laryngeal
      squamous cell cancer and 133 healthy controls were enrolled. Polymerase chain
      reaction-restriction fragment length polymorphism analysis was used to determine
      the CCDN1 genotypes. RESULTS: No significant association was detected between
      CCDN1 genotypes and laryngeal squamous cell cancer (LxSCCa) development.
      Similarly CCDN1 genotypes were not related to clinical parameters of Lx SCCa.
      However, there was a very significant association between CCDN1 G allele and
      presence of perineural invasion (p= 0.003; OR: 1.464; CI% 1.073-1.999). CCDN1 G
      allele frequency was significantly higher in the individuals with perineural
      invasion (85.7%) when compared to those without (58.5%). The 2 patients who died
      of disease were both found to possess the GG genotype. CONCLUSIONS: These results
      pose a controversy in suggesting a protective role of the G allele against LxSCCa
      development and support the association of CCDN1 gene GG genotype with mortality
      in patients with LxSCCa.

PMID- 24460345
TI  - Sperm-associated antigen 9 is a promising marker for early diagnosis of
      endometrial cancer.
AB  - BACKGROUND: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a
      novel biomarker for early diagnosis of several human tumors, including ovarian,
      cervical and breast cancers. Its clinical value remains to be clarified for
      endometrial cancer (EC). In this study, we investigated the utility of serum
      SPAG9 levels in diagnosis of EC and its association with important
      clinicopathological parameters. MATERIALS AND METHODS: This cross-sectional study
      was performed at a tertiary women's referral center in Ankara, Turkey.
      Preoperative serum samples were collected from patients surgically treated for
      endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy
      proven benign endometrium were used as controls. Serum SPAG9 levels were measured
      with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links
      with clinicopathological factors. Receiver operating characteristic (ROC) curve
      analysis was performed to assess power of SPAG9 levels for EC prediction. P
      values less than 0.05 were considered statistically significant. RESULTS: A total
      of 63 women with EC and 27 with benign endometrium were included in the study.
      Mean age in the EC group was 58.7+/-1.1. Median SPAG9 levels in the EC and
      control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3),
      respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence
      of malignant endometrium with 74% sensitivity and 83% specificity [Area under
      curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant
      association with histological type, FIGO stage, tumor grade, size, myometrial
      invasion, lymphovascular space invasion, cervical involvement, adnexal
      involvement, peritoneal cytology or lymph node status (all p>0.05). CONCLUSIONS:
      Testing for SPAG9 may be useful for early detection of EC in asymptomatic high
      risk women. Its role in post-treatment follow-up and early detection of
      recurrence should be assessed in future trials.

PMID- 24460346
TI  - Qualitative assessment of breast cancer early detection services provided through
      well woman clinics in the district of Gampaha in Sri Lanka.
AB  - BACKGROUND: Breast cancer is the most common cancer diagnosed among women in Sri
      Lanka. Early detection can lead to reduction in morbidity and mortality. The
      objective here was to identify perceptions of public health midwives (PHMs) on
      the importance of early detection of breast cancer and deficiencies of and
      suggestions on improving existing breast cancer early detection services provided
      through Well Woman Clinics. MATERIALS AND METHODS: A qualitative study using four
      focus group discussions (FGDs) were conducted among 38 PHMs in the Gampaha
      district in Sri Lanka and the meetings were audio-recorded, transcribed and
      analyzed using constant comparison and identifying themes and categories.
      RESULTS: All the PHMs had a firm realization on the need of breast cancer early
      detection. The four FGDs among PHMs revealed non-availability of guidelines,
      inadequacy of training, lack of skills and material to provide health education,
      inability to provide privacy during clinical examination, shortage of stationery,
      lack of community awareness and motivation. The suggestions for the improvements
      of the programme identified in FGDs were capacity building of PHMs, making
      availability of guidelines, rescheduling clinics, improving the supervision,
      strengthening the monitoring, improving coordination between clinical and
      preventive sectors, and improving community awareness. CONCLUSIONS: Results of
      the FGDs can provide useful information on components to be improved in breast
      cancer early detection services. Study recommendations were training programmes
      at basic and post basic levels on a regular basis and supervision for the
      sustainance of the breast cancer early detection program.

PMID- 24460347
TI  - Prognostic significance of peripheral blood flow cytometry parameters in patients
      with non-metastatic breast cancer.
AB  - BACKGROUND: Immune functions and their relation to prognosis in breast cancer
      patients have become areas of great interest in recent years. Correlations
      between survival outcomes and peripheral blood flow cytometry parameters are
      therefore of interest. Here we focused on patients with non-metastatic breast
      cancer (BC). MATERIALS AND METHODS: A total of 29 patients with pathological
      confirmed breast carcinoma and flow cytometry data were assessed for overall
      survival (OS) and progression free survival (PFS). RESULTS: The median age of the
      patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was
      significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26,
      p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef
      12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI,
      coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R
      Sq(adj)=67%. Similar findings were obtained for PFS. CONCLUSIONS: OS and PFS were
      significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4,
      HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic
      CD markers and absolute cytotoxic T cell number may be a prognostic factors in
      women with non-metastatic BC.

PMID- 24460349
TI  - Colorectal cancer screening among government servants in Brunei Darussalam.
AB  - BACKGROUND: This study concerns uptake and results of colorectal cancer (CRC)
      screening of government servant as part of the Health Screening Program that was
      conducted in Brunei Darussalam in 2009. MATERIALS AND METHODS: Government
      servants above the age of 40 or with family history of CRC were screened with a
      single fecal occult blood test (FIT, immunohistochemistry). Among 11,576 eligible
      subjects, 7,360 (66.9%) returned their specimen. Subjects with positive family
      history of CRC (n=329) or polyps (n=135) were advised to attend clinics to
      arrange screening. All the subjects with positive FIT (n=142, 1.9%) were referred
      to the endoscopy unit for counselling for screening colonoscopy. RESULTS: Overall
      only 17.7% of eligible subjects attended for screening; 54.9% (n=79/142) of
      positive FIT, 8.8% (n=29/329) of positive family history of CRC and none with
      history of polyps (n=0/135). Of these, only 54 patients (50.5%) agreed for
      colonoscopy, 52 (48.6%) declined as they were asymptomatic, and one was not
      offered (0.9%) due to his very young age. On screening colonoscopy, 12.9% (n=7)
      had advanced lesions including a sigmoid carcinoma in situ and six advanced
      polyps. The other findings included non advanced polyps (n=21), diverticular
      (n=11) and hemorrhoids (n=26). One patient who missed his screening colonoscopy
      appointment re-presented two years later and was diagnosed with advanced right
      sided CRC. All the advanced lesions were detected in patients with positive FIT,
      giving a yield of 20.5% for advanced lesions including cancers in the 5.1% FIT
      positive subjects. CONCLUSIONS: Our study showed screening for CRC even with a
      single FIT was effective. However, the uptake rate was poor with just over half
      of the patients agreeing to screening colonoscopy. Measures to increase public
      awareness are important. Since one limitation of our study was the relatively
      small sample size, larger studies should be conduced in future.

PMID- 24460348
TI  - Angiogenesis markers in breast cancer--potentially useful tools for priority
      setting of anti-angiogenic agents.
AB  - BACKGROUND: Breast cancer is the most common malignancy among women in both
      developed and developing countries. The burden is increasing in low-income and
      middle-income countries (LMCs) and threatens the public health of such societies.
      Introduction of expensive monoclonal antibodies to cancer treatment regimens
      poses a real challenge in the health systems of LMCs. Despite controversy of cost
      effectiveness of bevacizumab in breast cancer, some studies indicate gain of
      patients from this drug. The present study aimed to propose a priority setting
      model for administration of anti-angiogenic agents in breast cancer via
      assessment of tumor angiogenesis by the microvessel density (MVD) method and
      associations with clinicopathological characteristics (including simultaneous
      mutations of TP53 and HER-2 genes). MATERIALS AND METHODS: Age, axillary lymph
      nodes status, tumor size, stage and grade, estrogen and progesterone receptors
      status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation,
      Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed
      in 111 breast cancer patients. The molecular subtype of each tumor was also
      determined and correlations of simultaneous mutations of HER-2 and p53 genes with
      angiogenesis and other clinicopathological characteristics were evaluated.
      RESULTS: There were significant associations between simultaneous mutations of
      HER-2 and p53 genes and all other parameters except tumor size. The degree of
      angiogenesis in the ERBB2 subtype was greater than the others. Younger patients
      showed a higher angiogenesis rate rather those older than 50 years. CONCLUSIONS:
      Our results demonstrated that patients with simultaneous mutations of HER-2 and
      p53 genes, those with ERBB2 molecular subtype and also younger women (often
      triple negative) seem more eligible for obtaining anti-angiogenic agents. These
      results suggest a model for priority setting of patients with breast cancer for
      treatment with anti-angiogenic drugs in LMCs.

PMID- 24460350
TI  - What Turkish nurses know and do about skin cancer and sun protective behavior.
AB  - BACKGROUND: Skin cancer is a global health problem that can be prevented by
      protective behavior promoted by nurses. In Turkey, only few studies have examined
      current knowledge of nurses related to skin cancer and to reveal their attitudes
      towards sun exposure and current protective behavior. MATERIALS AND METHODS: This
      descriptive cross-sectional study was performed from March 11 to May 30, 2013
      with a study sample of 310 nurses working in two state hospitals located in
      Karabuk and Safranbolu. RESULTS: Mean age of the nurses was 30.3+/-6.89 years and
      96.1% of them had graduated with a Bachelor degree. The participants were
      predominantly female (n=284). Knowledge level about skin cancer was significantly
      higher for females compared to males. CONCLUSIONS: Nurses do not have sufficient
      knowledge about skin cancer and are not adequately protecting themselves from
      ultraviolet light, the primary risk factor for skin cancer. While they
      demonstrated a responsible attitude towards avoiding sunburn and the need for
      adequate sun protection, they do not fully appreciate the extent to which the sun
      can cause skin cancer and that they lack full understanding about the need to
      protect the skin from burning and to avoid long term sun exposure in Turkey.

PMID- 24460351
TI  - Quality of life in ovarian cancer patients choosing to receive salvage
      chemotherapy or palliative treatment.
AB  - BACKGROUND: The hypothesis that patients who primarily progress on two
      consecutive chemotherapy regimens without evidence of clinical benefit may opt
      for supportive care was investigated. The purpose was to determine the quality of
      life in recurrent ovarian cancer patients choosing to receive salvage
      chemotherapy in addition to supportive care or palliative care alone. A secondary
      objective was to evaluate factors that affect quality of life in ovarian cancer
      patients. MATERIALS AND METHODS: A descriptive study was conducted in patients
      who had histological confirmed epithelial ovarian cancer and failed to respond to
      at least one regimen of chemotherapy, coming for treatment at the King
      Chulalongkorn Memorial Hospital in Bangkok, Thailand over a six-month period from
      August 2012-March 2013. Each patient was asked to complete the FACT-G and a
      general personal questionnaire. The median quality of life score was analyzed.
      The Mann Whitney U Test was used to compare the difference between salvage
      chemotherapy and palliative care groups, and the Kruskal Wallis was used to
      evaluate other variables. RESULTS: Thirty-eight ovarian cancer patients were
      identified who failed to respond to chemotherapy. Of the 38, 30 chose salvage
      chemotherapy and eight palliative care for further treatment. By histology the
      carcimnomas were predominantly endometrioid subtype and poorly differentiated.
      The majority of patients in this study had FIGO stage III, and ECOG status 0-1.
      The median quality of life score was 76.3 (35.8-94.0), with no significant
      differences between the groups. Factors associated with the quality of life were
      the ECOG score and number of chemotherapeutic courses. CONCLUSIONS: In the
      setting of refractory or recurrent epithelial ovarian cancer, patients who
      receive salvage chemotherapy have comparable quality of life scores with patients
      treated with palliative care alone, providing a contrast with previous studies.

PMID- 24460352
TI  - Prevalence of aflatoxin induced p53 mutation at codon 249 (R249s) in
      hepatocellular carcinoma patients with and without hepatitis B surface antigen
      (HBsAg).
AB  - BACKGROUND: A missense mutation in exon 7 (R249S) of the p53 tumor suppressor
      gene is characteristic of aflatoxin B1 (AFB1) exposure. AFB1 is believed to have
      a synergistic effect on hepatitis virus B (HBV) carcinogenesis. However, results
      of studies comparing R249S prevalence among patients are conflicting. The aim of
      this study was to determine the prevalence of the R249S mutation in
      hepatocellular carcinoma (HCC) patients with or without positive HBsAg. MATERIALS
      AND METHODS: Paraffin embedded liver tissues were obtained from 124 HCC patients
      who underwent liver resection and liver biopsy in King Chulalongkorn Memorial
      Hospital. Restriction fragment length polymorphism (RFLP) was utilized to detect
      the R249S mutation. Positive results were confirmed by direct sequencing.
      RESULTS: Sixty four (52%) patients were positive for HBsAg and 18 (15%) were anti
      HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were
      confirmed to be R249S positive by Sanger sequencing (AGG to AGT). Out of these
      10, six were HBsAg positive, and out of the remaining 4, two were anti-HCV
      positive. The R249S prevalence among HCC patients with positive HBsAg was 9.4%
      compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation
      were younger (55+/-10 vs 60+/-13 year-old) and tended to have a more advanced
      Edmonson-Steiner grade of HCC, although differences did not reach statistical
      significance. CONCLUSIONS: Our study shows moderate prevalence of aflatoxin B1
      related p53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status
      was not associated with R249S prevalence.

PMID- 24460353
TI  - Immunoregulatory function of HLA-G in gastric cancer.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-G-positive gastric cancers are
      associated with poor survival, but links with tumor escape mechanisms remain to
      be determined. MATERIALS AND METHODS: We used immunohistochemistry to investigate
      HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52
      gastric cancer patients. RESULTS: There were 29 cancer-related deaths during the
      follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G
      positive (n=16) primary tumors had a significantly poorer prognosis than patients
      with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14
      months and 47 months, respectively. Patients with high numbers of Tregs and low
      numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than
      those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034,
      p=0.043). Multivariate Cox proportional hazard regression analysis showed that
      HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723;
      p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715;
      p=0.041) were independent unfavorable factors for patient survival. CONCLUSIONS:
      We found a significant positive correlation between HLA-G expression and the
      number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the
      number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells
      from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T
      lymphocytes.

PMID- 24460354
TI  - Prevalence, awareness, control, and treatment of hypertension and diabetes in
      korean cancer survivors: a cross-sectional analysis of the fourth and fifth Korea
      national health and nutrition examination surveys.
AB  - BACKGROUND: Management of hypertension and diabetes in cancer survivors is an
      important issue; however, not much is known about the level of management of such
      chronic disease in Korea. This study therefore assessed the prevalence,
      awareness, control, and treatment of hypertension and diabetes in Korean cancer
      survivors compared to non-cancer survivors. MATERIALS AND METHODS: A cross
      sectional design was employed, wherein data were obtained from standardized
      questionnaires completed by 943 cancer survivors and 41,233 non-cancer survivors
      who participated in the Fourth and Fifth Korea National Health and Nutrition
      Examination Surveys (2007-2011). We calculated adjusted proportions for
      prevalence and management of hypertension and diabetes in non-cancer survivors
      and cancer survivors. We also assessed the associated factors with prevalence and
      management of cancer survivors. RESULTS: Cancer survivors are more likely than
      the general population to have higher prevalence, awareness, treatment, and
      control of hypertension. However, diabetic management was not significantly
      higher in cancer survivors than in non-cancer survivors, despite their having a
      higher prevalence. Several factors, such as, age, drinking, years since cancer
      diagnosis, self-perceived health status, and specific cancer types were found to
      affect to management of hypertension and diabetes. CONCLUSIONS: These data
      suggest that cancer survivors appear to be better than non-cancer survivors at
      management of hypertension, but not diabetes. There is a need for healthcare
      providers to recognize the importance of long-term chronic disease management for
      cancer survivors and for the care model to be shared between primary care
      physicians and oncologists.

PMID- 24460355
TI  - Perceived susceptibility, and cervical cancer screening benefits and barriers in
      malaysian women visiting outpatient clinics.
AB  - AIMS: A main reason for increasing incidence of cervical cancer worldwide is the
      lack of regular cervical cancer screening. Coverage and uptake remain major
      challenges and it is crucial to determine the perceived susceptibility to
      cervical cancer, as well as the benefits of, and barriers to, cervical cancer
      screening among women. MATERIALS AND METHODS: A cross-sectional survey was
      conducted among 369 women attending an outpatient centre in Malaysia and data
      were collected by administering a self-report questionnaire. RESULTS: The
      majority of the participants (265, 71.8%) showed good level of perception of
      their susceptibility to cervical cancer. Almost all responded positively to four
      statements about the perceived benefits of cervical cancer screening (agree,
      23.1% or strongly agree, 52.5%), whereas negative responses were received from
      most of the participants (agree, 29.9%or strongly agree, 14.6 %) about the eleven
      statements on perceived barriers. Significant associations were observed between
      age and perceived susceptibility(x2=9.030, p=0.029); between employment status
      (p<0.001) as well as ethnicity and perceived benefits (p<0.05 [P=0.003]); and
      between education and perceived barriers to cervical cancer screening (p<0.001).
      CONCLUSIONS: Perceived susceptibility, including knowledge levels and personal
      risk assessment, should be emphasized through education and awareness campaigns
      to improve uptake of cervical cancer screening in Malaysia.

PMID- 24460356
TI  - Cost-effectiveness analysis of granisetron-based versus standard antiemetic
      regimens in low-emetogenic chemotherapy: a hospital-based perspective from
      Malaysia.
AB  - BACKGROUND: In a prospective cohort study of antiemetic therapy conducted in
      Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with
      or without granisetron injections as the primary prophylaxis for chemotherapy
      induced nausea and vomiting (CINV). This study is a retrospective cost analysis
      of two antiemetic regimens from the payer perspective. MATERIALS AND METHODS:
      This cost evaluation refers to 2011, the year in which the observation was
      conducted. Direct costs incurred by hospitals including the drug acquisition,
      materials and time spent for clinical activities from prescribing to dispensing
      of home medications were evaluated (MYR 1=$0.32 USD). As reported to be
      significantly different between two regimens (96.1% vs 81.0%; p=0.017), the
      complete response rate of acute emesis which was defined as a patient
      successfully treated without any emesis episode within 24 hours after LEC was
      used as the main indicator for effectiveness. RESULTS: Antiemetic drug
      acquisition cost per patient was 40.7 times higher for the granisetron-based
      regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for
      materials and clinical activities were included, the total cost per patient was
      8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47).
      Considering the complete response rates, the mean cost per successfully treated
      patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The
      incremental cost-effectiveness ratio (ICER) with granisetron-based regimen,
      relative to the standard regimen, was MYR 430.7. It was found to be most
      sensitive to the change of antiemetic effects of granisetron-based regimen.
      CONCLUSIONS: While providing a better efficacy in acute emesis control, the low
      incidence of acute emesis and high ICER makes use of granisetron as primary
      prophylaxis in LEC controversial.

PMID- 24460357
TI  - Methylation profile of BRCA1, RASSF1A and ER in Vietnamese women with ovarian
      cancer.
AB  - DNA methylation is considered a promising biomarkers for diagnosis of cancer in
      general and of ovarian cancer in particular. In our study, we validated the
      accuracy of methylation specific polymerase chain reaction (MSP) to analyze the
      methylation pattern of BRCA1, RASSF1A and ER in 59 and 10 Vietnamese patients
      with epithelial ovarian cancer (EOC) and benign ovarian tumors, respectively. We
      found methylation of BRCA1, RASSF1A and ER in 11/59 (18.6%), 40/59 (67.8%) and
      15/59 (25.4%) of EOC cases, while methylation of BRCA1 was only detected in 2/10
      (20%) benign ovarian patients. Forty five out of the 59 EOCs (78%) demonstrated
      methylation at one or more genes. The methylation frequency of RASSF1A was
      significantly associated with EOC (p<0.0005). No significant association was
      observed between methylation status of these genes and the clinical and
      pathological parameters of tumors collected from Vietnamese women suffering from
      ovarian cancer. 

PMID- 24460358
TI  - siRNA-mediated silencing of survivin inhibits proliferation and enhances
      etoposide chemosensitivity in acute myeloid leukemia cells.
AB  - BACKGROUND: Overexpression of survivin, a known inhibitor of apoptosis, is
      associated with tumor progression and drug resistance in numerous malignancies,
      including leukemias. The aim of this study was to investigate the effect of a
      specific survivin small interference RNA (siRNA) on proliferation and the
      sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic
      drug etoposide. MATERIALS AND METHODS: The cells were transfected with siRNAs
      using LipofectamineTM2000 transfection reagent. Relative survivin mRNA and
      protein levels were measured by quantitative real-time PCR and Western blotting,
      respectively. Trypan blue exclusion assays were performed to monitor tumor cell
      proliferation after siRNA transfection. The cytotoxic effects of etoposide and
      survivin siRNA, alone and in combination, on leukemic cells were determined using
      MTT assay. Apoptosis was assessed by ELISA cell death assay. RESULTS: Survivin
      siRNA markedly reduced both mRNA and protein expression levels in a time
      dependent manner, leading to distinct inhibition of cell proliferation and
      increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically
      increased the cell toxic effects of etoposide. Moreover, survivin down-regulation
      significantly enhanced its induction of apoptosis. CONCLUSIONS: Our study
      suggests that down-regulation of survivin by siRNA can trigger apoptosis and
      overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an
      effective adjuvant in AML chemotherapy.

PMID- 24460359
TI  - Policy effects of secondhand smoke exposure in public places in the Republic of
      Korea: evidence from PM2.5 levels and air nicotine concentrations.
AB  - OBJECTIVE: The purpose of this study was to evaluate secondhand smoke (SHS)
      exposure inside selected public places to provide basic data for the development
      and promotion of smoke-free policies. METHODS: Between March and May 2009, an SHS
      exposure survey was conducted. PM2.5 levels and air nicotine concentrations were
      measured in hospitals (n=5), government buildings (4), restaurants (10) and
      entertainment venues (10) in Seoul, Republic of Korea, using a common protocol.
      Field researchers completed an observational questionnaire to document evidence
      of active smoking (the smell of cigarette smoke, presence of cigarette butts and
      witnessing people smoking) and administered a questionnaire regarding building
      characteristics and smoking policy. RESULTS: Indoor PM2.5 levels and air nicotine
      concentrations were relatively higher in monitoring sites where smoking is not
      prohibited by law. Entertainment venues had the highest values of PM2.5(MUg/m3)
      and air nicotine concentration(MUg/m3), which were 7.6 and 67.9 fold higher than
      those of hospitals, respectively, where the values were the lowest. When evidence
      of active smoking was present, the mean PM2.5 level was 104.9 MUg/m3, i.e., more
      than 4-fold the level determined by the World Health Organization for 24-hr
      exposure (25 MUg/m3). Mean indoor air nicotine concentration at monitoring sites
      with evidence of active smoking was 59-fold higher than at sites without this
      evidence (2.94 MUg/m3 vs. 0.05 MUg/m3). The results were similar at all specific
      monitoring sites except restaurants, where mean indoor PM2.5 levels did not
      differ at sites with and without active smoking evidence and indoor air nicotine
      concentrations were higher in sites without evidence of smoking. CONCLUSION:
      Nicotine was detected in most of our monitoring sites, including those where
      smoking is prohibited by law, such as hospitals, demonstrating that enforcement
      and compliance with current smoke-free policies in Korea is not adequate to
      protect against SHS exposure.

PMID- 24460360
TI  - Comparison of mammography in combination with breast ultrasonography versus
      mammography alone for breast cancer screening in asymptomatic women.
AB  - AIM: To compare the agreement of screening breast mammography plus ultrasound and
      reviewed mammography alone in asymptomatic women. MATERIALS AND METHODS: All
      breast imaging data were obtained for women who presented for routine medical
      checkup at National Cancer Institute (NCI), Thailand from January 2010 to June
      2013. A radiologist performed masked interpretations of selected mammographic
      images retrieved from the computer imaging database. Previous mammography,
      ultrasound reports and clinical data were blinded before film re-interpretation.
      Kappa values were calculated to assess the agreement between BIRADS assessment
      category and BIRADS classification of density obtained from the mammography with
      ultrasound in imaging database and reviewed mammography alone. RESULTS: Regarding
      BIRADS assessment category, concordance between the two interpretations were
      good. Observed agreement was 96.1%. There was moderate agreement in which the
      Kappa value was 0.58% (95%CI; 0.45, 0.87). The agreement of BI-RADS
      classification of density was substantial, with a Kappa value of 0.60 (95%CI;
      0.54, 0.66). Different results were obtained when a subgroup of patients aged
      >=60 years were analyzed. In women in this group, observed agreement was 97.6%.
      There was also substantial agreement in which the Kappa value was 0.74% (95%CI;
      0.49, 0.98). CONCLUSIONS: The present study revealed that concordance between
      mammography plus ultrasound and reviewed mammography alone in asymptomatic women
      is good. However, there is just moderate agreement which can be enhanced if age-
      targeted breast imaging is performed. Substantial agreement can be achieved in
      women aged >=60. Adjunctive breast ultrasound is less important in women in this
      group.

PMID- 24460361
TI  - Clinicopathology significance of p53 and p63 expression in Indonesian cervical
      squamous cell carcinomas.
AB  - BACKGROUND: Human papilloma virus infection is associated with genesis and
      malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to
      p53 and retinoblastoma gene products, abrogating their functions as tumor
      suppressors, leading to an abnormal cell cycle machinery. Roles of the p53
      homolog p63 have also been postulated, E6 expression leading to TAp63b
      degradation allowing anchorage independent growth. Molecular studies correlated
      with clinicopathological factors are important to determine prognosis and
      treatment strategies, but results have been controversial and need to be
      clarified. AIM: To investigate expression of p53 and p63 in cervical squamous
      cell carcinomas in correlation with age, FIGO staging, morphology, and cancer
      cell proliferation. MATERIALS AND METHODS: Expression of p53 and p63
      immunohistochemical staining in a total of 56 paraffin-embedded tissues of
      cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia,
      was evaluated for correlation with clinicopathological parameters. The Mann
      Whitney test was used to compare the percentage of p53 and p63 expression with
      patient age, FIGO staging and morphology and to compare mean p53 and p63
      expression. The Spearman correlation test was applied to correlate p53 and p63
      expression with that of Ki-67. A p-value of <0.05 was considered statistically
      significant. RESULTS: There were significant associations between p53 expression
      with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki
      67 expression. There were no links between p63 expression and age, morphology,
      FIGO staging or Ki-67. CONCLUSIONS: This study indicated that p53 has a
      prognostic value in cervical squamous cell carcinomas given the relation with
      FIGO staging.

PMID- 24460362
TI  - 30 Years of radiotherapy service in Southern Thailand: workload vs resources.
AB  - BACKGROUND: To study the pattern of patient load, personnel and equipment
      resources from 30-years experience in Southern Thailand. MATERIALS AND METHODS:
      This retrospective study collected secondary data from the Division of
      Therapeutic Radiology and Oncology and the Songklanagarind Hospital Tumor
      Registry database, Faculty of Medicine, Prince of Songkla University, during the
      period of 1982-2012. RESULTS: The number of new patients who had radiation
      treatment gradually increased from 121 in 1982 to 2,178 in 2011. Shortages of all
      kinds of personnel were demonstrated as compared to the recommendations,
      especially in radiotherapy technicians. In 2011, Southern Thailand, with two
      radiotherapy centers, had 0.44 megavoltage radiotherapy machines (cobalt or
      linear accelerator) per million of population. This number is suboptimal, but
      could be managed cost-effectively by prolonging machine operating times during
      personnel shortages. CONCLUSIONS: This study identified a discrepancy between
      workload and resources in one medical school radiotherapy center in.

PMID- 24460364
TI  - Multi-agent systems: effective approach for cancer care information management.
AB  - Physicians, in order to study the causes of cancer, detect cancer earlier,
      prevent or determine the effectiveness of treatment, and specify the reasons for
      the treatment ineffectiveness, need to access accurate, comprehensive, and timely
      cancer data. The cancer care environment has become more complex because of the
      need for coordination and communication among health care professionals with
      different skills in a variety of roles and the existence of large amounts of data
      with various formats. The goals of health care systems in such a complex
      environment are correct health data management, providing appropriate information
      needs of users to enhance the integrity and quality of health care, timely access
      to accurate information and reducing medical errors. These roles in new systems
      with use of agents efficiently perform well. Because of the potential capability
      of agent systems to solve complex and dynamic health problems, health care
      system, in order to gain full advantage of E- health, steps must be taken to make
      use of this technology. Multi-agent systems have effective roles in health
      service quality improvement especially in telemedicine, emergency situations and
      management of chronic diseases such as cancer. In the design and implementation
      of agent based systems, planning items such as information confidentiality and
      privacy, architecture, communication standards, ethical and legal aspects,
      identification opportunities and barriers should be considered. It should be
      noted that usage of agent systems only with a technical view is associated with
      many problems such as lack of user acceptance. The aim of this commentary is to
      survey applications, opportunities and barriers of this new artificial
      intelligence tool for cancer care information as an approach to improve cancer
      care management. 

PMID- 24460363
TI  - Association of nutritional status with quality of life in breast cancer
      survivors.
AB  - Nutritional status and dietary intake play a significant role in the prognosis of
      breast cancer and may modify the progression of disease. The aim of this study
      was to determine the influence of nutritional status on the quality of life of
      Iranian breast cancer survivors. Cross-sectional data were collected for 100
      Iranian breast cancer survivors, aged 32 to 61 years, attending the oncology
      outpatient clinic at Golestan Hospital, Ahvaz, Iran. Nutritional status of
      subjects was assessed by anthropometric measurements, Patient-Generated
      Subjective Global Assessment (PG-SGA) and three non-consecutive 24-hour diet
      recalls. The European Organization of Research and Treatment of Cancer Quality of
      Life form (EORTC QLQ-C30) was used to assess quality of life. Ninety-four percent
      of the survivors were well-nourished, 6% were moderately malnourished or
      suspected of being malnourished while none were severely malnourished. Prevalence
      of overweight and obesity was 86%. Overall, participants had an inadequate intake
      of vitamin D, E, iron and magnesium according to dietary reference intake (DRI)
      recommendations. Survivors with better nutritional status had better functioning
      scales and experienced fewer clinical symptoms. It appears important to provide
      educational and nutritional screening programs to improve cancer survivor quality
      of life. 

PMID- 24460365
TI  - Reasons for variation in sensitivity and specificity of visual inspection with
      acetic acid (VIA) for the detection of pre- cancer and cancer lesions of uterine
      cervix.
AB  - Alternative strategies such as visual inspection of cervix with acetic acid, are
      real time, economical and easily implemented methods for cervical cancer
      screening. However, variable sensitivity and specificity have been observed in
      various community based studies. The possible reasons could include variation in
      man power training, light source used for visualization, and preparation of
      diluted (4-5%) acetic acid and its storage. A standardized protocol for training,
      teaching material (easy to understand in the local language) for trainees,
      supervision and reinforcement by intermittent and supplementary training to check
      the quality of their observation, a standard protocol for preparation dilute
      acetic acid and its storage and a standard good light source (equivalent to day
      light) are needed to minimize the variation in sensitivity and specificity of VIA
      in community settings. 

PMID- 24460366
TI  - IL-33, an important biomarker in non-small-cell lung cancer?

PMID- 24460367
TI  - Insulin resistance is associated with lower acetylcholine-induced microvascular
      reactivity in nondiabetic women.
AB  - BACKGROUND: The association between insulin resistance and microvascular
      dysfunction is well established in obese individuals with type 2 diabetes. It is
      unclear whether this relationship is dependent on obesity and body fat in insulin
      resistant persons. This study investigated acetylcholine (ACh)-induced
      microvascular reactivity in apparently healthy women (n=37, 20-45 years), with
      and without insulin resistance. METHODS: Body fat mass (dual X-ray
      absorptiometry), waist circumference (WC), blood pressure, fasting glucose,
      insulin, and free fatty acid concentrations were measured. Insulin resistance was
      estimated using homeostasis model assessment of insulin resistance (HOMA-IR), and
      subjects were divided into insulin-resistant (IR, n=16) and insulin-sensitive
      (IS, n=21) groups. ACh-induced forearm microvascular reactivity was measured by
      laser Doppler imagery using iontophoresis of ACh and compared between groups
      adjusting for WC and skin resistance (SR). RESULTS: The IR group had a higher
      body mass index (BMI) (30.7 +/- 6.4 vs. 22.9 +/- 7.3 kg/m(2), P < 0.01), fat mass
      (34.7 +/- 11.9 vs. 19.7 +/- 9.6 kg, P < 0.01), WC (89.9 +/- 13.6 vs. 74.4 +/- 9.7
      cm, P < 0.01), and a lower SR (0.24 +/- 0.08 vs. 0.32 +/- 0.08 Omega, P < 0.05)
      than the IS group. Microvascular reactivity, expressed as percentage increase in
      perfusion from baseline, was significantly lower in IR subjects after adjusting
      for differences in WC and SR (420.9 +/- 166.5 vs. 511.6 +/- 214.8%, P < 0.05).
      There were associations between microvascular reactivity and SR (r=-0.34, P <
      0.05) and systolic blood pressure (r=-0.36, P < 0.05), but not BMI, body fat
      mass, WC, or HOMA-IR. CONCLUSION: ACh-induced microvascular reactivity was
      different between IR and IS apparently healthy, nondiabetic women once
      differences in WC and SR were accounted for.

PMID- 24460371
TI  - Synthesis and characterization of [5]cycloparaphenylene.
AB  - The synthesis of highly strained [5]cycloparaphenylene ([5]CPP), a structural
      unit of the periphery of C60 and the shortest possible structural constituent of
      the sidewall of a (5,5) carbon nanotube, was achieved in nine steps in 17%
      overall yield. The synthesis relied on metal-mediated ring closure of a
      triethylsilyl (TES)-protected masked precursor 1c followed by removal of the TES
      groups and subsequent reductive aromatization. UV-vis and electrochemical studies
      revealed that the HOMO-LUMO gap of [5]CPP is narrow and is comparable to that of
      C60, as predicted by theoretical calculations. The results suggest that [5]CPP
      should be an excellent lead compound for molecular electronics. 

PMID- 24460370
TI  - Relationship between IL1 gene polymorphisms and periodontal disease in Japanese
      women.
AB  - Epidemiological evidence on the relationship between IL1A and/or IL1B
      polymorphisms and periodontal disease is inconsistent. We investigated
      associations between three IL1 single-nucleotide polymorphisms (SNPs) in genes
      encoding interleukin (IL) -1alpha (rs1800587) and IL-1beta (rs1143634 and
      rs16944) and the risk of periodontal disease among young Japanese women. A case
      control study was performed with a total of 1150 women, including 131 subjects
      who had at least one tooth with a probing pocket depth of 4 mm or deeper and 1019
      periodontally healthy controls. Compared with a reference group of women with the
      GG genotype of SNP rs16944, those with the GA genotype had a significantly
      reduced risk of periodontal disease, while there was no significant relationship
      between the AA genotype and periodontal disease. No evident relationships were
      observed between SNP rs1800587 or rs1143634 and periodontal disease. Our study
      did not reveal any evidence of interaction between the IL1 polymorphisms and
      smoking. The results of this study showed that the heterozygous variant genotype
      of the IL1 rs16944 was significantly associated with a reduced risk of
      periodontal disease in young Japanese women. Smoking did not significantly modify
      the gene-disease associations under study. 

PMID- 24460372
TI  - Hybrid assemblies of fluorescent nanocrystals and membrane proteins in liposomes.
AB  - Because of the growing potential of nanoparticles in biological and medical
      applications, tuning and directing their properties toward a high compatibility
      with the aqueous biological milieu is of remarkable relevance. Moreover, the
      capability to combine nanocrystals (NCs) with biomolecules, such as proteins,
      offers great opportunities to design hybrid systems for both nanobiotechnology
      and biomedical technology. Here we report on the application of the micelle-to
      vesicle transition (MVT) method for incorporation of hydrophobic, red-emitting
      CdSe@ZnS NCs into the bilayer of liposomes. This method enabled the construction
      of a novel hybrid proteo-NC-liposome containing, as model membrane protein, the
      photosynthetic reaction center (RC) of Rhodobacter sphaeroides. Electron
      microscopy confirmed the insertion of NCs within the lipid bilayer without
      significantly altering the structure of the unilamellar vesicles. The resulting
      aqueous NC-liposome suspensions showed low turbidity and kept unaltered the
      wavelengths of absorbance and emission peaks of the native NCs. A relative NC
      fluorescence quantum yield up to 8% was preserved after their incorporation in
      liposomes. Interestingly, in proteo-NC-liposomes, RC is not denatured by Cd-based
      NCs, retaining its structural and functional integrity as shown by absorption
      spectra and flash-induced charge recombination kinetics. The outlined strategy
      can be extended in principle to any suitably sized hydrophobic NC with similar
      surface chemistry and to any integral protein complex. Furthermore, the proposed
      approach could be used in nanomedicine for the realization of theranostic systems
      and provides new, interesting perspectives for understanding the interactions
      between integral membrane proteins and nanoparticles, i.e., in nanotoxicology
      studies. 

PMID- 24460373
TI  - Confusion of fear and surprise: a test of the perceptual-attentional limitation
      hypothesis with eye movement monitoring.
AB  - Of the basic emotional facial expressions, fear is typically less accurately
      recognised as a result of being confused with surprise. According to the
      perceptual-attentional limitation hypothesis, the difficulty in recognising fear
      could be attributed to the similar visual configuration with surprise. In effect,
      they share more muscle movements than they possess distinctive ones. The main
      goal of the current study was to test the perceptual-attentional limitation
      hypothesis in the recognition of fear and surprise using eye movement recording
      and by manipulating the distinctiveness between expressions. Results revealed
      that when the brow lowerer is the only distinctive feature between expressions,
      accuracy is lower, participants spend more time looking at stimuli and they make
      more comparisons between expressions than when stimuli include the lip stretcher.
      These results not only support the perceptual-attentional limitation hypothesis
      but extend its definition by suggesting that it is not solely the number of
      distinctive features that is important but also their qualitative value. 

PMID- 24460375
TI  - Structural basis for substrate specificity in ArnB. A key enzyme in the polymyxin
      resistance pathway of Gram-negative bacteria.
AB  - Cationic Antimicrobial Peptides (CAMPs) represent a first line of defense against
      bacterial colonization. When fighting Gram-negative bacteria, CAMPs initially
      interact electrostatically with the negatively charged phosphate groups in lipid
      A and are thought to kill bacteria by disrupting their membrane integrity.
      However, many human pathogens, including Salmonella and Pseudomonas , have
      evolved lipid A modification mechanisms that result in resistance to CAMPs and
      related antibiotics such as Colistin. The addition of 4-amino-4-deoxy-l-Arabinose
      (Ara4N) to a phosphate group in lipid A is one such modification, frequently
      found in Pseudomonas isolated from cystic fibrosis patients. The pathway for
      biosynthesis of Ara4N-lipid A requires conversion of UDP-Glucuronic acid into UDP
      Ara4N and subsequent transfer of the amino-sugar to lipid A. ArnB is a pyridoxal
      phosphate (PLP) dependent transaminase that catalyzes a crucial step in the
      pathway: synthesis of UDP-Ara4N from UDP-4-keto-pentose. Here we present the 2.3
      A resolution crystal structure of an active site mutant of ArnB (K188A) in
      complex with the reaction intermediate aldimine formed by UDP-Ara4N and PLP. The
      sugar-nucleotide binding site is in a cleft between the subunits of the ArnB
      dimer with the uracil buried at the interface and the UDP ribose and phosphate
      groups exposed to the solvent. The Ara4N moiety is found in the (4)C1
      conformation and its positioning, stabilized by interactions with both the
      protein and cofactor, is compatible with catalysis. The structure suggests
      strategies for the development of specific inhibitors that may prove useful in
      the treatment of resistant bacteria such as Pseudomonas found in cystic fibrosis
      patients. 

PMID- 24460377
TI  - Neuroprotective action of deer bone extract against glutamate or Abeta1-42
      induced oxidative stress in mouse hippocampal cells.
AB  - Water extracts of deer bone, called nokgol in Korean, and deer antlers have been
      traditionally used as anti-aging medicines. Deer antler extract is known to
      possess various activities, including anti-aging or anti-amnesic activity.
      However, there are no reports about the neuroprotective effect of deer bone
      extract (DBE). The objective of this study was to examine the neuroprotective
      effect of DBE on glutamate-induced cell death of mouse hippocampal cells (HT-22
      cells) and to elucidate the mode of neuroprotective action of DBE. In this study,
      HT-22 cells was pretreated with DBE before stimulation with glutamate, and then,
      the effects of DBE on cell viability, oxidative stress markers, and MAP kinases
      were determined. Separately, the effect of DBE on H2O2 or amyloid beta peptide (1
      42) (Abeta1-42)-induced cytotoxicity of HT-22 cells was evaluated. DBE protected
      HT-22 cells from glutamate-induced cell death and prevented the increase in
      lactate dehydrogenase leakage in HT-22 cells. DBE also prevented glutamate
      induced oxidative stress, as indicated by increased reactive oxygen species and
      lipid peroxidation as well as by decreases in glutathione (GSH) levels and GSH
      peroxidase activity. In addition, DBE inhibited glutamate-induced activation of c
      Jun N-terminal kinases (JNK), p38, and extracellular signal-regulated kinase,
      indicators of oxidative stress-induced cell death. Furthermore, DBE also
      protected against H2O2 and Abeta1-42-induced cytotoxicity. These results suggest
      that DBE may be a useful functional agent for the prevention against
      neurodegenerative disorders involving oxidative stress.

PMID- 24460378
TI  - Electron transfer through 3D monolayers on Au25 clusters.
AB  - The monolayer protecting small gold nanoparticles (monolayer-protected clusters,
      MPCs) is generally represented as the 3D equivalent of 2D self-assembled
      monolayers (SAMs) on extended gold surfaces. However, despite the growing
      relevance of MPCs in important applied areas, such as catalysis and nanomedicine,
      our knowledge of the structure of 3D SAMs in solution is still extremely limited.
      We prepared a large series of monodisperse Au25(SCnH2n+1)18 clusters (n=2, 4, 6,
      8, 10, 12, 14, 16, 18) and studied how electrons tunnel through these monolayers.
      Electron transfer results, nicely supported by 1H NMR spectroscopy, IR absorption
      spectroscopy, and molecular dynamics results, show that there is a critical
      ligand length marking the transition between short ligands, which form a quite
      fluid monolayer structure, and longer alkyl chains, which self-organize into
      bundles. At variance with the truly protecting 2D SAMs, efficient electronic
      communication of the Au25 core with the outer environment is thus possible even
      for long alkyl chains. These conclusions provide a different picture of how an
      ultrasmall gold core talks with the environment through/with its protecting but
      not-so-shielding monolayer.

PMID- 24460379
TI  - A novel method to evaluate error in anatomical marker placement using a modified
      generalized Procrustes analysis.
AB  - As biomechanical research evolves, a continuing challenge is the standardization
      of data collection and analysis techniques. In gait analysis, placement of
      markers to construct an anatomical model has been identified as the single
      greatest source of error; however, there is currently no standardized approach to
      quantifying these errors. The current study applies morphometric methods,
      including a generalized Procrustes analysis (GPA) and a nearest neighbour
      comparison to quantify discrepancies in marker placement, with the goal of
      improving reliability in gait analysis. An extensive data-set collected by an
      Expert (n = 340) was used to evaluate marker placements performed by a Novice (n
      = 55). Variances identified through principal component analysis were used to
      create a modified GPA to transform anatomical data, and scaled coordinates from
      the Novice data-set were then scored against the Expert subset. The results
      showed quantitative differences in marker placement, suggesting that, although
      training improved consistency, systematic biases remained.

PMID- 24460380
TI  - Methods of teaching - revisited experiential diaries and learning logs.
AB  - This is the twenty-sixth in a series of articles on methods of teaching. Readers
      ere encouraged to share their experiences with teaching methods not included in
      this series. 

PMID- 24460381
TI  - Proposed trade agreements would make policy implications of environmental
      research entirely irrelevant.

PMID- 24460382
TI  - Response to: Strong ion approach in cardiogenic shock: formula and patients.

PMID- 24460383
TI  - Theoretical prediction of hydrogen-bond basicity pKBHX using quantum chemical
      topology descriptors.
AB  - Hydrogen bonding plays an important role in the interaction of biological
      molecules and their local environment. Hydrogen-bond strengths have been
      described in terms of basicities by several different scales. The pKBHX scale has
      been developed with the interests of medicinal chemists in mind. The scale uses
      equilibrium constants of acid...base complexes to describe basicity and is
      therefore linked to Gibbs free energy. Site specific data for polyfunctional
      bases are also available. The pKBHX scale applies to all hydrogen-bond donors
      (HBDs) where the HBD functional group is either OH, NH, or NH+. It has been found
      that pKBHX can be described in terms of a descriptor defined by quantum chemical
      topology, DeltaE(H), which is the change in atomic energy of the hydrogen atom
      upon complexation. Essentially the computed energy of the HBD hydrogen atom
      correlates with a set of 41 HBAs for five common HBDs, water (r2=0.96), methanol
      (r2=0.95), 4-fluorophenol (r2=0.91), serine (r2=0.93), and methylamine (r2=0.97).
      The connection between experiment and computation was strengthened with the
      finding that there is no relationship between DeltaE(H) and pKBHX when hydrogen
      fluoride was used as the HBD. Using the methanol model, pKBHX predictions were
      made for an external set of bases yielding r2=0.90. Furthermore, the basicities
      of polyfunctional bases correlate with DeltaE(H), giving r2=0.93. This model is
      promising for the future of computation in fragment-based drug design. Not only
      has a model been established that links computation to experiment, but the model
      may also be extrapolated to predict external experimental pKBHX values.

PMID- 24460388
TI  - In vitro genotoxicity of fipronil sister chromatid exchange, cytokinesis block
      micronucleus test, and comet assay.
AB  - Fipronil (FP) is a phenylpyrazole pesticide developed by the transnational
      company Rhone-Poulenc Agro in 1987. Data on the genotoxicity and toxicity of FP
      are rather inadequate. In this study, we aimed to evaluate the potential
      genotoxic activity of FP using the single-cell microgel electrophoresis or comet
      assay, sister chromatid exchanges (SCEs), and micronuclei (MN) in human
      peripheral blood lymphocytes. In addition, the cytokinesis block proliferation
      index (CBPI) and proliferation index (PRI) were measured for cytotoxicity. In
      this study, three different doses of FP were used (0.7, 0.3, 0.1 MUg/mL).
      Mitomycin C (2 MUg/mL) and hydrogen peroxide were used as positive controls for
      SCE MN test systems, and comet assay, respectively. FP induced a statistically
      significant increase in the MN and SCE frequency and DNA damage in a dose
      dependent manner in human peripheral blood lymphocytes (p<0.01, p<0.05, for 0.7
      and 0.3 MUg/mL, respectively) compared with a negative control. There is no
      significant difference between 0.1 MUg/mL and the negative control for MN
      frequency, but there is significant difference between all the doses of FP and
      negative control for SCE frequency, mitotic index, CBPI, and PRI values (p<0.01).
      Using the alkaline comet assay, we showed that all the doses of the FP induced
      DNA damage in human peripheral blood lymphocytes in vitro (p<0.05).

PMID- 24460392
TI  - Overgrowth of gold nanorods by using a binary surfactant mixture.
AB  - Seed-mediated surfactant-assisted growth is widely used as the most effective
      method for gold nanorod (NR) synthesis. Using prepared nanorods as seeds for
      further overgrowth can increase the dimensional tunability of the final
      particles. However, overgrowth in usual cetyltrimethylammonium bromide (CTAB)
      surfactant solutions leads to poor control of the final particle shape and size.
      In this work, we report an improved strategy to demonstrate the controllable
      overgrowth of gold NRs in the binary surfactant mixture sodium oleate (NaOL) +
      CTAB. This approach overcomes the difficulty of growing NR suspensions with small
      amounts of impurities. By controlling the total amount of added NR seeds, it is
      possible to tune the average length, diameter, and plasmon resonances of
      overgrown particles in a wide range. Together with the original NaOL + CTAB
      method developed by Murray and co-workers ( Nano Lett. 2013 , 13 , 555 ), this
      overgrowth approach expands the dimensional and plasmonic tunability of the
      fabrication technology without any decrease in the monodispersity and purity of
      samples. 

PMID- 24460391
TI  - General holistic impairment in congenital prosopagnosia: evidence from Garner's
      speeded-classification task.
AB  - Congenital prosopagnosia (CP), a lifelong impairment in face processing in the
      absence of brain damage, is often ascribed to impairment in holistic processing.
      It is still debated whether such difficulties are restricted to faces or whether
      they can also be observed for nonfacial stimuli. Here, we investigate this issue
      by examining CP individuals and their controls on two variations of the Garner
      speeded classification task tailored to assess holistic processing of nonfacial
      stimuli. In Experiment 1, participants were asked to judge the width of visually
      presented rectangles while ignoring their irrelevant height, or to judge changes
      in width while height remained constant. Critically, while controls exhibited the
      expected Garner interference, no such interference was observed for the CPs,
      indicating impaired holistic processing of integral, nonfacial shape dimensions.
      Experiment 2, utilized the same Garner paradigm, but here participants were asked
      to judge integral dimensions that are unrelated to shape (colour). Importantly,
      both CPs and controls exhibited the same level of Garner interference, indicating
      intact integral processing of colour dimensions. This dissociation between the
      performance on the two Garner tasks indicates that CPs do not exhibit a general
      local processing bias or impaired integration of any perceptual dimensions, but
      rather a deficit that is restricted to tasks requiring holistic integral
      perception of shape dimensions. Taken together, these results provide evidence
      for the existence of a general impairment in holistic shape perception in CP,
      which may be related to the mechanisms underlying this disorder. 

PMID- 24460393
TI  - Target gene knockdown by 2',4'-BNA/LNA antisense oligonucleotides in zebrafish.
AB  - Gene knockdowns using oligonucleotide-based approaches are useful for studying
      gene function in both in vitro cell culture systems and in vivo animal models. We
      evaluated the efficacy of 2',4'-bridged nucleic acids (BNA)-modified antisense
      oligonucleotides (AONs) for gene knockdown in zebrafish. We used the tcf7l1a gene
      as a model for testing the knockdown efficacy of 2',4'-BNA AONs and examined how
      the target sites/affinity and RNase H induction activity of 2',4'-BNA AONs affect
      knockdown efficacy. We found that tcf7l1a gene function was knocked down by 2',4'
      BNA AONs that target the start codon and induce RNase H activity. Although
      nonspecific p53-mediated developmental defects were observed at higher doses, the
      effective dose of the 2',4'-BNA AONs for tcf7l1a is much lower than that of
      morpholino oligonucleotides. Our data thus show a potential application for 2',4'
      BNA AONs in the downregulation of specific genes in zebrafish. 

PMID- 24460394
TI  - Surface EMG-force modelling for the biceps brachii and its experimental
      evaluation during isometric isotonic contractions.
AB  - The aim of this study was to evaluate a surface electromyography (sEMG) signal
      and force model for the biceps brachii muscle during isotonic isometric
      contractions for an experimental set-up as well as for a simulation. The proposed
      model includes a new rate coding scheme and a new analytical formulation of the
      muscle force generation. The proposed rate coding scheme supposes varying minimum
      and peak firing frequencies according to motor unit (MU) type (I or II).
      Practically, the proposed analytical mechanogram allows us to tune the force
      contribution of each active MU according to its type and instantaneous firing
      rate. A subsequent sensitivity analysis using a Monte Carlo simulation allows
      deducing optimised input parameter ranges that guarantee a realistic behaviour of
      the proposed model according to two existing criteria and an additional one. In
      fact, this proposed new criterion evaluates the force generation efficiency
      according to neural intent. Experiments and simulations, at varying force levels
      and using the optimised parameter ranges, were performed to evaluate the proposed
      model. As a result, our study showed that the proposed sEMG-force modelling can
      emulate the biceps brachii behaviour during isotonic isometric contractions.

PMID- 24460395
TI  - Separation of single-walled carbon nanotubes with a gel permeation chromatography
      system.
AB  - A gel permeation chromatography system is used to separate aqueous sodium dodecyl
      sulfate suspensions of single-walled carbon nanotubes (SWCNTs). This automated
      procedure requires no precentrifugation, is scalable, and is found to yield
      monochiral SWCNT fractions of semiconducting SWCNTs with a purity of 61-95%.
      Unsorted and resulting monochiral fractions are characterized using optical
      absorption and photoluminescence spectroscopy. 

PMID- 24460396
TI  - Response to "Letter to the editor concerning the viewpoint; 'Recognizing the
      limitations of performance reference compound (PRC)-calibration technique in
      passive water sampling'".

PMID- 24460398
TI  - Graduate preparation for continuing education.

PMID- 24460399
TI  - Molecular epidemiology of infectious laryngotracheitis: a review.
AB  - Infectious laryngotracheitis (ILT) is an economically important respiratory
      disease of poultry that affects the poultry industry worldwide. The disease is
      caused by gallid herpesvirus I (GaHV-1), a member of the genus Iltovirus, family
      Herpesviridae, subfamily Alphaherpesvirinae. The current incidence of the disease
      is heavily influenced by live attenuated vaccines, which have been used
      extensively since their introduction in the mid-twentieth century. The capability
      of current live attenuated vaccine viruses to revert to virulence and spread from
      bird to bird has shaped the molecular epidemiology of ILT. Because of the
      antigenic homogeneity among GaHV-1 strains, differentiation of strains has been
      achieved by targeting genomic differences between outbreak-related isolates and
      vaccine strains. Numerous genes and genomic regions have been utilized in the
      development of DNA-based diagnostic assays to differentiate outbreak-related
      isolates from vaccine strains in countries where ILT outbreaks have occurred.
      More recently, full genome sequences have allowed determination of the origin of
      some of the outbreak-related isolates circulating in some poultry production
      countries. Overall, molecular typing data collected worldwide have identified
      live attenuated vaccine-related isolates as the primary source for outbreaks of
      the disease. 

PMID- 24460400
TI  - Exciton characteristics in graphene epoxide.
AB  - Exciton characteristics in graphene epoxide (GE) are investigated by density
      functional theory with quasi-particle corrections and many-body interactions. The
      nature of the exciton is influenced by epoxide content and detailed geometric
      configurations. Two kinds of excitons are identified in GE: Frenkel-like exciton
      originated from the sp(2) carbon cluster and charge-transfer exciton formed by
      localized states involving both oxygen and carbon atoms. The unusual blue shift
      associated with the Frenkel-like exciton leaking is highlighted. One scaling
      relationship is proposed to address the power-law dependence of Frenkel-like
      exciton binding strength on its size. The charge-transfer exciton appears in GE
      samples with the high oxygen coverage. Particularly, the exciton in GE structures
      exhibits long lifetime by analyzing both radiative and nonradiative decay
      processes. This study sheds light on the potential applications of GE-based
      structures with attractive high quantum yield in light emission and
      optoelectronic technology. 

PMID- 24460401
TI  - Development and validation of a human biomechanical model for rib fracture and
      thorax injuries in blunt impact.
AB  - From 1990 to approximately 50,000-120,000 people die annually of road traffic
      accidents in China. Traffic accidents are the main cause of death of Chinese
      adults aged 15-45 years. This study aimed to determine the biomechanical response
      and injury tolerance of the human body in traffic accidents. The subject was a 35
      year-old male with a height of 170 cm, weight of 70 kg and Chinese
      characteristics at the 50th percentile. Geometry was generated by computed
      tomography and magnetic resonance imaging. A human-body biomechanical model was
      then developed. The model featured in great detail the main anatomical
      characteristics of skeletal tissues, soft tissues and internal organs, including
      the head, neck, shoulder, thoracic cage, abdomen, spine, pelvis, pleurae and
      lungs, heart, aorta, arms, legs, and other muscle tissues and skeletons. The
      material properties of all tissues in the human body model were obtained from the
      literature. Material properties were developed in the LS-DYNA code to simulate
      the mechanical behaviour of the biological tissues in the human body. The model
      was validated against cadaver responses to frontal and side impact. The predicted
      model response reasonably agreed with the experimental data, and the model can
      further be used to evaluate thoracic injury in real-world crashes. We believe
      that the transportation industry can use numerical models in the future to
      simultaneously reduce physical testing and improve automotive safety.

PMID- 24460404
TI  - Single- and double-layered organically modified nanosheets by selective
      interlayer grafting and exfoliation of layered potassium hexaniobate.
AB  - Organically modified niobate nanosheets are promising building blocks for the
      design of advanced hybrid materials. Nanosheets with controlled thickness and
      surface composition are important for precise structural design of the nanosheet
      based materials. In this work, single-layered and double-layered niobate
      nanosheets functionalized by phenylphosphonate moieties were selectively prepared
      by interlayer grafting of A-type and B-type intercalation derivatives of
      potassium hexaniobate (K4Nb6O17.3H2O) with phenylphosphonic acid (PPA), followed
      by exfoliation by ultrasonication in acetonitrile. The interlayer grafting of PPA
      was monitored using X-ray diffraction (XRD), Fourier transform infrared (FTIR),
      and solid-state NMR spectroscopy, and the thicknesses of the exfoliated
      nanosheets were measured by atomic force microscopy (AFM). Transparent hybrid
      films were obtained by incorporating the single- and double-layered nanosheets
      into an epoxy matrix. 

PMID- 24460405
TI  - Amelioration of psychiatric symptoms through exposure to music individually
      adapted to brain rhythm disorders - a randomised clinical trial on the basis of
      fundamental research.
AB  - INTRODUCTION: This pilot study examined, whether long-term exposure of
      psychiatric patients to music that was individually adapted to brain rhythm
      disorders associated with psychoticism could act to ameliorate psychiatric
      symptoms. METHODS: A total of 50 patients with various psychiatric diagnoses were
      randomised in a 1:1 ratio to listen to CDs containing either music adapted to
      brain rhythm anomalies associated with psychoticism - measured via a specific
      spectral analysis - or standard classical music. Participants were instructed to
      listen to the CDs over the next 18 months. Psychiatric symptoms in both groups
      were assessed at baseline and at 4, 8 and 18 months, using the Brief Symptom
      Inventory (BSI). RESULTS: At 18 months, patients in the experimental group showed
      significantly decreased BSI scores compared to control patients. Intriguingly,
      this effect was not only seen for symptoms of psychoticism and paranoia but also
      for anxiety, phobic anxiety and somatisation. CONCLUSIONS: Exposure to the
      adapted music was effective in ameliorating psychotic, anxiety and phobic anxiety
      symptoms. Based on the theories of neuroplasticity and brain rhythms, it can be
      hypothesised that this intervention may be enhancing brain-rhythm synchronisation
      and plasticity in prefrontal-hippocampal circuits that are implicated in both
      psychosis/paranoia and anxiety/phobic anxiety.

PMID- 24460407
TI  - Preventive effects of lignan extract from flax hulls on experimentally induced
      benign prostate hyperplasia.
AB  - Consumption of diet rich in lignans may decrease the risk of some chronic
      hormonal conditions such as benign prostatic hyperplasia (BPH). This study
      investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA
      (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat
      model. Male Wistar-Unilever rats were randomly divided into four groups of 12
      rats each: a negative control group fed with control diet and receiving daily
      subcutaneous injections of corn oil without TP, and three groups fed with control
      diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0)
      and receiving daily subcutaneous injections of TP in corn oil. Treatments with
      diets started 2 weeks before the induction of BPH and were carried out for 5
      consecutive weeks. The influence of TP and LLE on body weight (BW), food and
      water consumptions, and enterolactone (ENL) levels in serum and urine of rats was
      examined at the end of the 5-week treatment period. TP significantly diminished
      the mean body weight gain (MBWG) of positive control rats and their food and
      water consumptions while LLE reduced significantly this MBWG reduction in a dose
      dependent manner. The lignan-rich extract significantly inhibited TP-induced
      prostate size ratio (prostate weight/rat BW) increase in comparison with positive
      controls (P<.001). This effect was dose dependent. Higher serum and urine levels
      of ENL correlated well with the dose of extract provided to rats. It was
      concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH
      indicating it might be beneficial in the prevention of BPH.

PMID- 24460410
TI  - Pyrronazols, metabolites from the myxobacteria Nannocystis pusilla and N.
      exedens, are unusual chlorinated pyrone-oxazole-pyrroles.
AB  - The chlorinated pyrrole-oxazole-pyrones pyrronazol A (1), pyrronazol A2 (2), and
      pyrronazol B (3) were isolated from Nannocystis pusilla strain Ari7, and two
      chlorinated pyrrole-oxazole isomers, pyrronazols C1 (4) and C2 (5), were isolated
      from N. pusilla strain Na a174. HRESIMS, NMR, and X-ray crystallographic analysis
      was used in the structure elucidation including the absolute configuration of
      pyrronazol A (1). In addition to pyrronazols, 1,6-phenazine-diol (6) and its
      glycosyl derivative, 1-hydroxyphenazin-6-yl-alpha-d-arabinofuranoside (7), were
      isolated and identified from the culture broth of N. pusilla strain Ari7. When
      tested for biological activity against bacteria, fungi, and yeasts, 1 showed weak
      antifungal activity against Mucor hiemalis (MIC 33.3 MUg/mL) but no antibacterial
      activity, while 6 showed weak antibacterial and antifungal activity (MIC 33.3
      MUg/mL) against some of the strains tested. In cell culture experiments 1 showed
      no significant cytotoxicity, while 6 was active against several cell lines,
      especially the human ovarian carcinoma cells SK-OV-3 (LD50 2.59 MUM). 

PMID- 24460411
TI  - Introduction.
AB  - "The Impact of Continuing Education on the Nursing Profession" was developed as a
      presentation for the 1982 American Nurses' Association 53rd Convention held in
      Washington, D.C. The Executive Committee of the Council on Continuing Education
      developed the presentation, parts of which were not presented at the convention.
      The intent of the Executive Committee in sharing the following material is to
      provide a broad overview of the state-of-the-art and some projections of the
      future and to examine a few key issues in greater depth. The Journal of
      Continuing Education in Nursing welcomes responses and comments. 

PMID- 24460413
TI  - Rotational disorder in twisted bilayer graphene.
AB  - Conventional means of stacking two-dimensional (2D) crystals inevitably leads to
      imperfections. To examine the ramifications of these imperfections, rotational
      disorder and strain are quantified in twisted bilayer graphene (TBG) using a
      combination of Raman spectroscopic and low-energy electron diffraction imaging.
      The twist angle between TBG layers varies on the order of 2 degrees  within large
      (50-100 MUm) single-crystalline grains, resulting in changes of the emergent
      Raman response by over an order of magnitude. Rotational disorder does not evolve
      continuously across the large grains but rather comes about by variations in the
      local twist angles between differing contiguous subgrains, ~ 1 MUm in size, that
      themselves exhibit virtually no twist angle variation (DeltaTheta ~ 0.1 degrees
      ). Owing to weak out-of-plane van der Waals bonding between azimuthally rotated
      graphene layers, these subgrains evolve in conjunction with the 0.3% strain
      variation observed both within and between the atomic layers. Importantly, the
      emergent Raman response is altered, but not removed, by these extrinsic
      perturbations. Interlayer interactions are therefore resilient to strain and
      rotational disorder, a fact that gives promise to the prospect of designer 2D
      solid heterostructures created via transfer processes.

PMID- 24460414
TI  - Electrocardiogram signal quality assessment using an artificially reconstructed
      target lead.
AB  - In real applications, even the most accurate electrocardiogram (ECG) analysis
      algorithm, based on research databases, might breakdown completely if a quality
      measurement technique is not applied precisely before the analysis. The major
      concentration of this study is to describe and develop a reliable ECG signal
      quality assessment technique. The proposed algorithm includes three major stages:
      preprocessing, energy-concavity index (ECI) analysis and a correlation-based
      examination subroutine. The preprocessing step includes the removal of baseline
      wanders and high-frequency disturbances. The quality measurement based on ECI
      includes two separate stages according to the energy and concavity of the ECG
      signal. The correlation-based quality measurement step is mainly established by
      using the correlation between ECG leads estimated by applying a suitably trained
      neural network. The operating characteristics of the proposed ECI are sensitivity
      (Se) of 77.04% with a positive predictive value (PPV) of 90.53% for detecting
      high-energy noise. The correlation-based technique achieved the best scores (Se =
      100%; PPV = 98.92%) for detecting high-energy noise and for recognising any other
      kind of disturbances (Se = 92.36%; PPV = 94.77%). Although ECI analysis acts
      effectively against high-energy disturbances, very poor performance is obtained
      in cases where the energy of the disturbances is not considerable. However, the
      correlation-based method is able to find all kinds of disturbances. For
      officially evaluating the proposed algorithm, an entry was sent to the Computing
      in-Cardiology Challenge 2011 on 27 February 2012; a final score (accuracy) of
      93.60% was achieved.

PMID- 24460415
TI  - Epinephrine, DNA integrity and oxidative stress in workers exposed to extremely
      low-frequency electromagnetic fields (ELF-EMFs) at 132 kV substations.
AB  - There is apprehension about widespread use of electrical and electromagnetic
      gadgets which are supposed to emit electromagnetic radiations. Reports are
      controversy. These electromagnetic fields (EMFs) have considerable effect on
      endocrine system of exposed subjects. This study was focused to assess the
      possible bioeffects of extremely low-frequency (ELF)-EMFs on epinephrine level,
      DNA damage and oxidative stress in subjects occupationally exposed to 132 kV high
      voltage substations. The blood sample of 142 exposed subjects and 151 non-exposed
      individuals was analyzed. Plasma epinephrine was measured by enzyme-linked
      immunosorbent assay, DNA damage was studied by alkaline comet assay along with
      oxidative stress. Epinephrine levels of sub-groups showed mean concentration of
      75.22  +/-  1.46, 64.43  +/-  8.26 and 48.47  +/-  4.97 for high, medium and low
      exposed groups, respectively. DNA damage ranged between 1.69 um and 9.91 um. The
      oxidative stress levels showed significant increase. The individuals employed in
      the live-line procedures were found to be vulnerable for EM stress with altered
      epinephrine concentrations, DNA damage and increased oxidative stress.

PMID- 24460416
TI  - The effects of long-term exposure to a 2450 MHz electromagnetic field on growth
      and pubertal development in female Wistar rats.
AB  - The aim of this study was to investigate the effects of a 2450 MHz
      electromagnetic field (EMF) (wireless internet frequency) on the growth and
      development of female Wistar rats. The study was conducted on three groups of
      rats. The prenatal and postnatal groups were exposed to EMF 1 h/day beginning
      from intrauterine and postnatal periods, respectively. The third group was the
      sham-exposed group. Growth, nutrition and vaginal opening (VO) were regularly
      monitored. Serum and tissue specimens were collected at puberty. Histological
      examinations, total antioxidant status (TAS), total oxidant status (TOS) and
      oxidative stress index (OSI) measurements in ovary and brain tissues and also
      immunohistochemical staining of the hypothalamus were performed besides the
      determination of serum FSH, LH, E2 and IGF-1 values. Birth masses of the groups
      were similar (p > 0.05). Mass gain per day was significantly lower and the
      puberty was significantly later in the prenatal group. Brain and ovary TOS and
      OSI values in the prenatal group were significantly increased (p < 0.05) compared
      to the control group. Serum LH levels of the prenatal and postnatal groups were
      increased, although serum FSH, and E2 values did not differ among the groups (p >
      0.05). Histological examinations of the specimens revealed no statistically
      significant difference between the groups (p > 0.05). Exposure to 2450 MHz EMF,
      particularly in the prenatal period, resulted in postnatal growth restriction and
      delayed puberty in female Wistar rats. Increased TOS and OSI values in the brain
      and ovary tissues can be interpreted as a sign of chronic stress induced by EMF.
      This is the first longitudinal study which investigates the effects of EMF
      induced by wireless internet on pubertal development beside growth.

PMID- 24460417
TI  - Analysis of estimation of electromagnetic dosimetric values from non-ionizing
      radiofrequency fields in conventional road vehicle environments.
AB  - A high number of wireless technologies can be found operating in vehicular
      environments with the aim of offering different services. The dosimetric
      evaluation of this kind of scenarios must be performed in order to assess their
      compatibility with current exposure limits. In this work, a dosimetric evaluation
      inside a conventional car is performed, with the aid of an in-house 3D Ray
      Launching computational code, which has been compared with measurement results of
      wireless sensor networks located inside the vehicle. These results can aid in an
      adequate assessment of human exposure to non-ionizing radiofrequency fields,
      taking into account the impact of the morphology and the topology of the vehicle
      for current as well as for future exposure limits.

PMID- 24460418
TI  - Comparative experiments on phantom and ex vivo liver tissue in microwave
      ablation.
AB  - PURPOSE: The aim of this study is to investigate the thermal field distribution
      of phantom and ex vivo liver tissue in microwave ablation. We intent to verify if
      the phantom can be used in future studies in lieu of actual tissue. METHODS: This
      experiment was divided into two groups of phantom and ex vivo porcine liver
      tissue. 2450 MHz is set. The tests last up to 240 s in 60 W. The velocity of the
      circulating water pumps were adjusted to 40 rounds/min. Twenty-five copper
      constantan thermocouples (TCs) were inserted at the specified position to record
      temperature data. RESULT: For the cooling water, the temperature field was non
      symmetric distribution at the gap before (z > z < 0 mm) of two groups of
      experiments. At the part without cooling water (z > 0 mm), effective ablation
      areas were larger; near the microwave antenna, the temperature curves showed good
      consistency for both materials. Far away from the microwave antenna, the value
      difference increased between phantom and liver tissue. Moreover, the effect of
      cooling water in phantom is more obvious than it in liver tissue. The shapes of
      ablation areas from two groups are not same. CONCLUSION: The result of the
      present work implied that heating patterns of liver tissue and phantom are
      comparable. But the difference of temperature field between two kinds of
      materials cannot be ignored. In cases of using phantom to verify temperature
      field in lieu of actual tissue, the researchers should pay full attention to
      these difference points.

PMID- 24460419
TI  - Applicator modeling for electromagnetic thermotherapy of cervix cancer.
AB  - This report proposes an induction heating coil design that can be used for
      producing strong magnetic fields around ferromagnetic implants located in the
      cervix of uterus. The effect of coil design on the uniformity and extent of heat
      generation ability is inspected. Also, a numerical model of the applicator is
      developed that includes the ferromagnetic implants, and is coupled to the bioheat
      transfer model of the body tissue. Then, the ability of the proposed applicator
      for electromagnetic thermotherapy is investigated.

PMID- 24460420
TI  - Effects of rotating magnetic field exposure on the functional parameters of
      different species of bacteria.
AB  - The aim of the present study was to determine the effect of the rotating magnetic
      field (RMF) on the growth, cell metabolic activity and biofilm formation by S.
      aureus, E. coli, A. baumannii, P. aeruginosa, S. marcescens, S. mutans, C.
      sakazakii, K. oxytoca and S. xylosus. Bacteria were exposed to the RMF (RMF
      magnetic induction B = 25-34 mT, RMF frequency f = 5-50 Hz, time of exposure t =
      60 min, temperature of incubation 37  degrees C). The persistence of the effect
      of exposure (B = 34 mT, f = 50 Hz, t = 60 min) on bacteria after further
      incubation (t = 300 min) was also studied. The work showed that exposure to RMF
      stimulated the investigated parameters of S. aureus, E. coli, S. marcescens, S.
      mutans, C. sakazakii, K. oxytoca and S. xylosus, however inhibited cell metabolic
      activity and biofilm formation by A. baumannii and P. aeruginosa. The results
      obtained in this study proved, that the RMF, depending on its magnetic induction
      and frequency can modulate functional parameters of different species of
      bacteria.

PMID- 24460421
TI  - Effect of long-term exposure of 2.4 GHz radiofrequency radiation emitted from Wi
      Fi equipment on testes functions.
AB  - The aim of this study was to investigate long-term effects of radiofrequency
      radiation (RFR) emitted from a Wireless Fidelity (Wi-Fi) system on testes. The
      study was carried out on 16 Wistar Albino adult male rats by dividing them into
      two groups such as sham (n: 8) and exposure (n: 8). Rats in the exposure group
      were exposed to 2.4 GHz RFR radiation for 24 h/d during 12 months (1 year). The
      same procedure was applied to the rats in the sham control group except the Wi-Fi
      system was turned off. Immediately after the last exposure, rats were sacrificed
      and reproductive organs were removed. Motility (%), concentration (*10(6)/mL),
      tail defects (%), head defects (%) and total morphologic defects (%) of sperms
      and weight of testes (g), left epididymis (g), prostate (g), seminal vesicles (g)
      were determined. Seminiferous tubules diameter (MUm) and tunica albuginea
      thickness (MUm) were also measured. However, the results were evaluated by using
      Johnsen's score. Head defects increased in the exposure group (p < 0.05) while
      weight of the epididymis and seminal vesicles, seminiferous tubules diameter and
      tunica albuginea thickness were decreased in the exposure group (p < 0.01, p <
      0.001, p < 0.0001). However, other alterations of other parameters were not found
      significant (p > 0.05). In conclusion, we observed that long-term exposure of 2.4
      GHz RF emitted from Wi-Fi (2420 MUW/kg, 1 g average) affects some of the
      reproductive parameters of male rats. We suggest Wi-Fi users to avoid long-term
      exposure of RF emissions from Wi-Fi equipment.

PMID- 24460422
TI  - Placenta chorioangioma: a rare case and systematic review of literature.
AB  - OBJECTIVES: Placental chorioangioma is a relatively rare condition that often
      results in serious prenatal complications and adverse pregnancy outcome. We
      report a case of a large chorioangioma that was prenatally diagnosed at 23 weeks
      with polyhydramnios and fetal anemia. With prenatal monitoring, transplacental
      therapy with a COX-2 inhibitor and intrauterine transfusion, the pregnancy
      resulted in the live birth at 30 weeks. Due to the paucity of evidence relating
      to the management protocols in cases of placental chorioangiomas, we have
      conducted a systematic review of the literature. METHODS: All reported cases in
      the English language were captured using the electronic databases. Bibliographies
      of relevant articles were manually searched. RESULTS: Sixty-four articles were
      included reporting 112 cases of placental chorioangioma. In 79, there was no
      prenatal treatment and in 33 there was in-utero treatment. A systematic
      comparison of antenatal complications and pregnancy outcomes was performed. No
      strong conclusion could be made due to the low number and quality of the reported
      cases. CONCLUSION: Placenta chorioangioma represents a challenge with its
      potentially serious complications adversely affecting pregnancy outcome. An
      international registry of pregnancies with this rare complication and
      documentation of pregnancy outcomes will improve the evidence base for
      prospective management.

PMID- 24460428
TI  - Dynamic visualization of nanoscale vortex orbits.
AB  - Due to the atomic-scale resolution, scanning tunneling microscopy is an ideal
      technique to observe the smallest objects. Nevertheless, it suffers from very
      long capturing times in order to investigate dynamic processes at the nanoscale.
      We address this issue, for vortex matter in NbSe2, by driving the vortices using
      an ac magnetic field and probing the induced periodic tunnel current modulations.
      Our results reveal different dynamical modes of the driven vortex lattices. In
      addition, by recording and synchronizing the time evolution of the tunneling
      current at each pixel, we visualize the overall dynamics of the vortex lattice
      with submillisecond time resolution and subnanometer spatial resolution. 

PMID- 24460424
TI  - Paramedic intubation: patient position might matter.
AB  - OBJECTIVE: Paramedics often intubate in challenging environments. We evaluated
      whether patient position might affect prehospital intubation success rates
      utilizing a cadaver model. METHODS: The study was conducted in two phases: a
      cross-sectional survey and an experimental model in which paramedics were asked
      to demonstrate intubation skills on cadavers in three positions. New York State
      certified paid and volunteer paramedics and critical care emergency medical
      technicians were recruited from multiple agencies. To assess past experience,
      participants self-reported the number of patients they attempted to intubate in
      the previous 12 months and the patient positions in which they attempted those
      intubations. Participants attempted to intubate nonembalmed cadavers in a
      controlled environment in three positions: on the floor, on a low stretcher to
      simulate the patient care compartment of an ambulance, and on an elevated
      stretcher. Paramedics were allowed a maximum of three intubation attempts of one
      minute each per cadaver. Endotracheal tube placement was verified by a single
      attending emergency physician using direct visualization. RESULTS: Self-reports
      of intubation attempts in the previous 12 months indicated that participants had
      attempted to intubate a mean of 6.4 patients per paramedic. Self-reported
      positions of patient intubations were 57% on the floor, 33% in the ambulance, 7%
      on a stretcher of unspecified height, and 3% in some other position. During the
      study, 84 paramedics performed 251 intubations on 42 cadavers. First-attempt and
      cumulative first- and second-attempt success rates were 77.4 and 89.3% for the
      floor position, 74.7 and 94.0% for the low stretcher (ambulance) position, and
      86.9 and 96.4% for the elevated stretcher position, respectively. First attempt
      success was higher in the elevated stretcher position compared to the low
      stretcher position (OR = 2.25, 95% CI 1.01-5.00). No other position contributed
      to greater odds of ETI success either on the first or second attempt.
      CONCLUSIONS: Endotracheal intubation success was higher with the cadaver
      positioned on an elevated stretcher compared to a low stretcher. Paramedics must
      be aware of patient position when performing prehospital intubation.

PMID- 24460429
TI  - Synthesis and antiviral and fungicidal activity evaluation of beta-carboline,
      dihydro-beta-carboline, tetrahydro-beta-carboline alkaloids, and their
      derivatives.
AB  - Six known beta-carboline, dihydro-beta-carboline, and tetrahydro-beta-carboline
      alkaloids and a series of their derivatives were designed, synthesized, and
      evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for
      the first time. All of the alkaloids and some of their derivatives (compounds 3,
      4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral
      agent Ribavirin both in vitro and in vivo. Especially, the inactivation,
      curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3%
      at 500 MUg/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 MUg/mL) in
      vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500
      MUg/mL). A new derivative, 14, with optimized physicochemical properties,
      obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500
      MUg/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new
      lead structure for the development of anti-TMV drugs. Moreover, most of these
      compounds exhibited good fungicidal activity against 14 kinds of fungi,
      especially compounds 4, 7, and 11. 

PMID- 24460430
TI  - Bioengineered blood vessels.
AB  - Cardiovascular disease (CVD) affecting blood vessel function is a leading cause
      of death around the world. A common treatment option to replace the diseased
      blood vessels is vascular grafting using the patient's own blood vessels.
      However, patients with CVD are usually lacking vessels for grafting. Recent
      advances in tissue engineering are now providing alternatives to autologous
      vascular grafts in the form of tissue-engineered blood vessels (TEBVs). In this
      review, we will describe the use of different scaffolding systems, cell sources
      and conditioning approaches for creating fully functional blood vessels.
      Additionally, we will present the methods used for assessing TEBV functions and
      describe preclinical and clinical trials for TEBV. Although the early results
      were encouraging, current designs of TEBV still fall short as a viable clinical
      option. Implementing the current knowledge in vascular development can lead to
      improved fabrication and function of TEBV and hasten clinical translation. 

PMID- 24460433
TI  - Paracetamol effectiveness, safety and blood level monitoring during patent ductus
      arteriosus closure: a case series.
AB  - Paracetamol was reported to be effective for patent ductus arteriosus (PDA)
      closure. We present a case series of PDA closure by paracetamol in seven
      premature infants. During the treatment, paracetamol blood levels did not exceed
      the recommended levels for analgesia and hyperthermia in six tested infants. None
      of the patients demonstrated significant disturbances of liver function.

PMID- 24460434
TI  - Photoisomerization dynamics of stiff-stilbene in solution.
AB  - Photoinduced isomerization of 1,1'-bis-indanyliden (stiff-stilbene) in solution
      was studied with broadband transient absorption and femtosecond Raman
      spectroscopies, and by quantum-chemical calculations. Trans-to-cis S1
      isomerization proceeds over a 600 and 400 cm(-1) barrier in n-hexane and
      acetonitrile, respectively. The reaction develops on multiple time scales with
      fast (0.3-0.4 ps) viscosity-independent and slower (2-26 ps) viscosity-dependent
      components. In the course of intramolecular torsion (which should be the main
      reaction coordinate) some excited molecules pass through the perpendicular
      conformation P and reach the cis geometry, to be temporarily trapped there.
      Subsequently they relax back to P and further to the ground state S0. The cis-to
      trans isomerization reveals ultrafast (0.06 ps) oscillatory relaxation followed
      by 13 ps decay in n-hexane and 2 ps decay in acetonitrile, corresponding to
      barriers of 800 and 400 cm(-1), respectively. Raman S0 and S1 spectra are
      reported and discussed. The perpendicular conformation P was not detected,
      possibly due to its low oscillator strength and short lifetime, or because of
      strong overlap with hot product spectra. XMCQDPT2 calculations locate a
      stationary S1 point on the cis side and two perpendicular-pyramidalized
      stationary points, to be reached from the former over 300 and 680 cm(-1) barrier.
      Implications for parent stilbene are discussed; in this case we also see evidence
      for the trans-to-cis adiabatic path, as in stiff-stilbene. Very similar viscosity
      dependence for the two compounds supports the common isomerization pathway:
      torsion about the central double bond. 

PMID- 24460431
TI  - Penalizing hospitals for chronic obstructive pulmonary disease readmissions.
AB  - In October 2014, the U.S. Centers for Medicare and Medicaid Services (CMS) will
      expand its Hospital Readmission Reduction Program (HRRP) to include chronic
      obstructive pulmonary disease (COPD). Under the new policy, hospitals with high
      risk-adjusted, 30-day all-cause unplanned readmission rates after an index
      hospitalization for a COPD exacerbation will be penalized with reduced
      reimbursement for the treatment of Medicare beneficiaries. In this perspective,
      we review the history of the HRRP, including the recent addition of COPD to the
      policy. We critically assess the use of 30-day all-cause COPD readmissions as an
      accountability measure, discussing potential benefits and then highlighting the
      substantial drawbacks and potential unintended consequences of the measure that
      could adversely affect providers, hospitals, and patients with COPD. We conclude
      by emphasizing the need to place the 30-day COPD readmission measure in the
      context of a reconceived model for postdischarge quality and review several
      frameworks that could help guide this process. 

PMID- 24460436
TI  - Evaluation research.

PMID- 24460438
TI  - Macrolide use leads to clinical and radiological improvement in patients with
      cryptogenic organizing pneumonia.
AB  - Cryptogenic organizing pneumonia is an idiopathic form of organizing pneumonia
      (also known as bronchiolitis obliterans organizing pneumonia). Because
      cryptogenic organizing pneumonia is considered an inflammatory disease, it
      characteristically responds to the broad-spectrum antiinflammatory
      corticosteroids, although relapse is common on discontinued use. Additionally,
      long-term use of corticosteroids has many side effects. In severe cases in which
      corticosteroids have failed, either cytotoxic therapy or macrolide therapy is
      used. Because of the toxicity and adverse effects of cytotoxic therapy (e.g.,
      cyclophosphamide), this therapy option cannot be used long term in refractory
      cases. Macrolide therapy has been shown to be an effective antiinflammatory agent
      that is relatively safe when used on a long-term basis in patients with
      cryptogenic organizing pneumonia. 

PMID- 24460439
TI  - Kaposiform lymphangiomatosis, a newly characterized vascular anomaly presenting
      with hemoptysis in an adult woman.
AB  - Disorders of the pulmonary lymphatic system include macro- and microcystic
      lymphatic malformations, primary or secondary lymphangiectasias, generalized
      lymphatic anomalies, diffuse pulmonary lymphangiomatosis, and combinations of
      lymphatic and other tissue anomalies, including lymphangioleiomyomatosis (LAM).
      We report a case of a patient with a newly defined entity classified as
      kaposiform lymphangiomatosis (KLA). This 50-year-old nonsmoking Hispanic woman
      presented with a 20-year history of cough, hemoptysis, chyloptysis, and pleuritic
      chest pain. Laboratory evaluation demonstrated a low normal platelet count,
      elevated d-Dimer, low normal fibrinogen, and elevated fibrin split products.
      Chest computerized tomography imaging showed enlarged hypodense lymph nodes in
      the mediastinum and hila, and peribronchovascular thickening, without evidence of
      cystic parenchymal lesions. Magnetic resonance imaging of the chest showed cystic
      mediastinal lymph nodes with heterogeneously increased T2 and decreased T1 signal
      intensity. Fiberoptic bronchoscopy revealed hyperemic mucosa with granular
      appearance suggestive of a submucosal infiltrative process. Pathological
      specimens revealed dilated, malformed lymphatic channels within the pleura,
      pulmonary septa, and bronchovascular bundles, and foci of perilymphatic and
      intralymphatic spindle cells which reacted with the Prospero homeobox protein 1
      (PROX-1) immunostain. The morphology and immunohistochemistry results were
      consistent with a diagnosis of KLA. This newly recognized clinical-pathological
      entity among intrathoracic lymphatic anomalies is distinguished from generalized
      lymphatic anomaly and diffuse pulmonary lymphangiomatosis in part by
      characteristic hematological abnormalities and hemorrhagic complications,
      including hemoptysis, as experienced by our patient. 

PMID- 24460437
TI  - Inhaled amikacin for treatment of refractory pulmonary nontuberculous
      mycobacterial disease.
AB  - RATIONALE: Treatment of pulmonary nontuberculous mycobacteria, especially
      Mycobacterium abscessus, requires prolonged, multidrug regimens with high
      toxicity and suboptimal efficacy. Options for refractory disease are limited.
      OBJECTIVES: We reviewed the efficacy and toxicity of inhaled amikacin in patients
      with treatment-refractory nontuberculous mycobacterial lung disease. METHODS:
      Records were queried to identify patients who had inhaled amikacin added to
      failing regimens. Lower airway microbiology, symptoms, and computed tomography
      scan changes were assessed together with reported toxicity. MEASUREMENTS AND MAIN
      RESULTS: The majority (80%) of the 20 patients who met entry criteria were women;
      all had bronchiectasis, two had cystic fibrosis and one had primary ciliary
      dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M.
      abscessus and 5 for Mycobacterium avium complex and had received a median (range)
      of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a
      median of 19 (1, 50) months. Eight (40%) patients had at least one negative
      culture and 5 (25%) had persistently negative cultures. A decrease in smear
      quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of
      19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%),
      and worsened in four (20%). Improvement on computed tomography scans was noted in
      6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped
      amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and
      nephrotoxicity, persistent dysphonia, and vertigo in one each. CONCLUSIONS: In
      some patients with treatment-refractory pulmonary nontuberculous mycobacterial
      disease, the addition of inhaled amikacin was associated with microbiologic
      and/or symptomatic improvement; however, toxicity was common. Prospective
      evaluation of inhaled amikacin for mycobacterial disease is warranted.

PMID- 24460440
TI  - Treatment of pulmonary nontuberculous mycobacterial infections: many questions
      remain.

PMID- 24460441
TI  - Why aren't doctors following the environmental mycobacterial disease guidelines?

PMID- 24460442
TI  - An official multi-society statement: ventilator-associated events--the new
      definition.

PMID- 24460443
TI  - Self-management in chronic obstructive pulmonary disease. Time for a paradigm
      shift?
AB  - Self-management in chronic obstructive pulmonary disease, centering on an action
      plan for the exacerbation and enhanced communication between the patient and
      health care providers, makes good clinical sense. However, five relatively large
      trials of self-management in chronic obstructive pulmonary disease have had
      inconsistent results: only two demonstrated reductions in health care utilization
      and one had to be discontinued prematurely because of increased mortality. Do
      these discordant findings require a paradigm shift in our concept of self
      management? Probably not-but an analysis of the negative studies can give us
      valuable insights. There are data to support the idea that patients in the trial
      that showed increased mortality did not self-manage appropriately. Only 4.5% of
      these patients called in before starting treatment for their exacerbation, the
      time to initiation of antibiotics or steroids was unsatisfactorily long, and the
      intervention arm used minimally more prednisone and antibiotics than the control
      arm. The reasons for a higher mortality will likely never be known, but it is
      possible that these high-risk patients may have needed earlier assessment by a
      trained professional, or that self-management led to overconfidence and treatment
      delays. We clearly need more effective ways to implement self-management and
      better define which groups of patients stand to benefit (or be harmed) by this
      intervention. This will require an investment in well-thought-out clinical
      trials. 

PMID- 24460446
TI  - Intensive care ultrasound: V. Goal-directed echocardiography.

PMID- 24460445
TI  - Managing pulmonary nontuberculous mycobacterial infection. time for a patient
      centered approach.
AB  - The incidence of nontuberculous mycobacteria is increasing worldwide. However,
      the evidence base for clinical management comprises mostly expert opinion, case
      series, and few randomized clinical trials. Most currently recommended treatment
      regimens entail prolonged use of multiple antimicrobial agents associated with
      multiple self-limited and persistent potential adverse effects, including
      irreversible impairments of hearing, vision, and kidney function. Yet, little is
      known about how treatment impacts an individual patient's overall health status.
      Current treatment guidelines, although of undoubted value, are constrained by
      these limitations. Here we call for new studies that reassess recommendations for
      medical management of pulmonary nontuberculous mycobacteria infections, in
      particular Mycobacterium avium-intracellulare complex and Mycobacterium abscessus
      complex. We propose pragmatic, person-centered outcome measures that might be
      used in clinical assessments and new research studies, including patient-reported
      experience measures and patient-reported outcome measures. This will enable
      patients and their health-care providers to make clinical management decisions
      that derive from a realistic view of what they can hope to achieve from
      treatment. 

PMID- 24460444
TI  - Lung microbiome for clinicians. New discoveries about bugs in healthy and
      diseased lungs.
AB  - Microbes are readily cultured from epithelial surfaces of the skin, mouth, and
      colon. In the last 10 years, culture-independent DNA-based techniques
      demonstrated that much more complex microbial communities reside on most
      epithelial surfaces; this includes the lower airways, where bacterial culture had
      failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial
      environment is important for adequate immunological development. The most common
      microbes found in the lower airways are also found in the upper airways.
      Increasing abundance of oral characteristic taxa is associated with increased
      inflammatory cells and exhaled nitric oxide, suggesting that the airway
      microbiome induces an immunological response in the lung. Furthermore, rhinovirus
      infection leads to outgrowth of Haemophilus in patients with chronic obstructive
      pulmonary disease, and human immunodeficiency virus-infected subjects have more
      Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction
      in which the host immune defenses also influence the microbial niche.
      Quantitative and/or qualitative changes in the lung microbiome may be relevant
      for disease progression and exacerbations in a number of pulmonary diseases.
      Future investigations with longitudinal follow-up to understand the dynamics of
      the lung microbiome may lead to the development of new therapeutic targets. 

PMID- 24460447
TI  - Intensive care ultrasound: VI. Fluid responsiveness and shock assessment.

PMID- 24460448
TI  - A surreptitious trip to the lungs.

PMID- 24460449
TI  - Shell thickness modulation in ultrasmall CdSe/CdS(x)Se(1-x)/CdS core/shell
      quantum dots via 1-thioglycerol.
AB  - In this study, we report on the synthesis of CdSe/CdS core-shell ultrasmall
      quantum dots (CS-USQDs) using an aqueous-based wet chemistry protocol. The
      proposed chemical route uses increasing concentration of 1-thioglycerol to grow
      the CdS shell on top of the as-precipitated CdSe core in a controllable way. We
      found that lower concentration of 1-thioglycerol (3 mmol) added into the reaction
      medium limits the growth of the CdSe core, and higher and increasing
      concentration (5-11 mmol) of 1-thioglycerol promotes the growth of CdS shell on
      top of the CdSe core in a very controllable way, with an increase from 0.50 to
      1.25 nm in shell thickness. The growth of CS-USQDs of CdSe/CdS was confirmed by
      using different experimental techniques, such as optical absorption (OA)
      spectroscopy, fluorescence spectroscopy, X-ray diffraction, Fourier transform
      infrared spectroscopy, and Raman spectroscopy. Data collected from OA were used
      to obtain the average values of the CdSe core diameter, whereas Raman data were
      used to assess the average values of the CdSe core diameter and CdS shell
      thicknesses. 

PMID- 24460450
TI  - Progesterone reduces secondary damage, preserves white matter, and improves
      locomotor outcome after spinal cord contusion.
AB  - Progesterone is an anti-inflammatory and promyelinating agent after spinal cord
      injury, but its effectiveness on functional recovery is still controversial. In
      the current study, we tested the effects of chronic progesterone administration
      on tissue preservation and functional recovery in a clinically relevant model of
      spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we
      observed that progesterone reduced both volume and rostrocaudal extension of the
      lesion at 60 days post-injury. In addition, progesterone increased the number of
      total mature oligodendrocytes, myelin basic protein immunoreactivity, and the
      number of axonal profiles at the epicenter of the lesion. Further, progesterone
      treatment significantly improved motor outcome as assessed using the Basso
      Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data
      suggest that progesterone could be considered a promising therapeutical candidate
      for spinal cord injury.

PMID- 24460452
TI  - An ex vivo investigation into the transurothelial permeability and bladder wall
      distribution of the nonsteroidal anti-inflammatory ketorolac.
AB  - Transurothelial drug delivery continues to be an attractive treatment option for
      a range of urological conditions; however, dosing regimens remain largely
      empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory
      ketorolac has been shown to significantly reduce ureteral stent-related pain.
      While this latest development provides an opportunity for advancing the
      management of stent-related pain, clinical translation will undoubtedly require
      an understanding of the rate and extent of delivery of ketorolac into the bladder
      wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and
      bladder wall distribution of ketorolac. The subsequent application of a
      pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo.
      Ketorolac was applied to the urothelium and a transurothelial permeability
      coefficient (Kp) calculated. Relative drug distribution into the bladder wall
      after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp =
      2.63 * 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and
      21 MUg g(-1) were achieved in the urothelium, lamina propria and detrusor
      respectively. An average concentration of 87 MUg g(-1) was achieved across the
      whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo
      values for Kp and muscle/saline partition coefficient (providing an estimation of
      vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations.
      When dilution of the drug solution with urine and vascular clearance were taken
      into account, a reduced ketorolac concentration of 37 MUg g(-1) across the whole
      bladder wall was predicted. These studies reveal crucial information about the
      urothelium's permeability to agents such as ketorolac and the concentrations
      achievable in the bladder wall. It would appear that levels of ketorolac
      delivered to the bladder wall intravesically would be sufficient to provide an
      anti-inflammatory effect. The combination of such ex vivo data and PK modeling
      provides an insight into the likelihood of achieving clinically relevant
      concentrations of drug following intravesical administration. 

PMID- 24460451
TI  - Comparison of droperidol and haloperidol for use by paramedics: assessment of
      safety and effectiveness.
AB  - BACKGROUND: Since the 2001 "black box" warning on droperidol, its use in the
      prehospital setting has decreased substantially in favor of haloperidol. There
      are no studies comparing the prehospital use of either drug. The goal of this
      study was to compare QTc prolongation, adverse events, and effectiveness of
      droperidol and haloperidol among a cohort of agitated patients in the prehospital
      setting. METHODS: In this institutional review board-approved before and after
      study, we collected data on 532 patients receiving haloperidol (n = 314) or
      droperidol (n = 218) between 2007 and 2010. We reviewed emergency department (ED)
      electrocardiograms when available (haloperidol, n = 78, 25%; droperidol, n = 178,
      76%) for QTc length (in milliseconds), medical records for clinically relevant
      adverse events (defined a priori as systolic blood pressure (SBP) <90 mmHg,
      seizure, administration of anti-dysrhythmic medications, cardioversion or
      defibrillation, bag-valve-mask ventilation, intubation, cardiopulmonary arrest,
      and prehospital or in-hospital death). We also compared effectiveness of the
      medications, using administration of additional sedating medications within 30
      minutes of ED arrival as a proxy for effectiveness. RESULTS: The mean haloperidol
      dose was 7.9 mg (median 10 mg, range 4-20 mg). The mean droperidol dose was 2.9
      mg (median 2.5 mg, range 1.25-10 mg.) Haloperidol was given i.m. in 289 cases
      (92%), and droperidol was given i.m. in 132 cases (61%); in all other cases, the
      medication was given i.v.. There was no statistically significant difference in
      median QTc after medication administration (haloperidol 447 ms, 95% CI: 440-454
      ms; droperidol 454 ms, 95% CI: 450-457). There were no statistically significant
      differences in adverse events in the droperidol group as compared to the
      haloperidol group. One patient in the droperidol group with a history of
      congenital heart disease suffered a cardiopulmonary arrest and was resuscitated
      with neurologically intact survival. There was no significant difference in the
      use of additional sedating medications within 30 minutes of ED arrival after
      receiving droperidol (2.9%, 95% CI: -2.5-8.4%). CONCLUSIONS: In this cohort of
      agitated patients treated with haloperidol or droperidol in the prehospital
      setting, there was no significant difference found in QTc prolongation, adverse
      events, or need for repeat sedation between haloperidol and droperidol.

PMID- 24460453
TI  - Is methotrexate administration needed for the treatment of caesarean section scar
      pregnancy in addition to suction curettage?
AB  - OBJECTIVE: This study evaluated the clinical outcomes and safety of treating
      caesarean scar pregnancy (CSP) by means of suction curettage followed when
      required by Foley tamponade, with or without methotrexate (MTX) therapy preceding
      the curettage. METHODS: Twenty-five patients with CSP were identified between
      August 2008 and April 2012. The first team of doctors treated Group A patients (n
      = 11) with systemic MTX followed by dilatation and suction curettage whereas the
      second team of doctors carried out only a suction curettage on women of Group B
      (n = 14). If uncontrolled vaginal bleeding occurred in either group during or
      after the operation, a Foley catheter, guided by real time transabdominal
      ultrasound, was placed in the uterine cavity against the site where the CSP had
      been implanted. RESULTS: Clinical outcomes in the two groups - including mean
      estimated blood loss, major complication rate, and hospital length of stay - were
      comparable. Surgeons used Foley catheter balloons for tamponade in six of the 11
      patients in Group A and in seven of the 14 patients in Group B. Treatment was
      successful in ten of 11 cases in group A and 13 of 14 cases in group B. Group B's
      mean duration of treatment (2.36 +/- 0.49 days) was significantly shorter than
      that of Group A (14.45 +/- 4.96 days; p < 0.001). CONCLUSION: Suction curettage,
      followed when needed by Foley catheter tamponade, is an effective treatment for
      CSP.

PMID- 24460454
TI  - Accidental Unilateral Mydriasis from Hyoscine Patch in a Care Provider.
AB  - The hyoscine patch is effective and is frequently used in motion sickness
      treatment. Not uncommonly, it is used to control excessive respiratory secretions
      in palliative patients. Patients, healthcare workers, and caregivers who
      administer these may experience a benign, although worrying, mydriasis should
      they inadvertently rub their eye after handling the patch. A 46-year-old staff
      nurse working in a stroke ward presented with sudden-onset unilateral enlarged
      pupil. To rule out any intracranial pathology, the stroke team requested an
      urgent head computed tomography (CT) scan, which showed no abnormality. Upon
      ophthalmology review, nonreactive dilated left pupil was noted. Examination was
      otherwise unremarkable with no focal neurology findings. Following further
      history, she recalled applying a hyoscine patch to a patient in the morning. Two
      days later, her left pupil returned to normal size. This unique presentation of
      pharmacological mydriasis reinforces the importance of a detailed targeted
      history to avoid unnecessary investigations and anxiety, as well as the
      importance of informing patients, healthcare workers, and caregivers of this
      peculiar side-effect. 

PMID- 24460458
TI  - Litigation in obstetrics: does defensive medicine contribute to increases in
      cesarean delivery?
AB  - OBJECTIVE: Obstetrics is one of the most sued subspecialties in the US. This
      study aimed to examine clinicians' medical-legal experience and its association
      with recommending cesarean delivery. DESIGN: Cross-sectional convenience survey.
      POPULATION OR SAMPLE: This is a survey study of clinicians in the US. METHODS:
      Survey included eight common obstetric clinical vignettes and 27 questions
      regarding clinicians' practice environment. Chi-square test, multivariable
      logistic regression models were used for statistical comparisons. MAIN OUTCOME
      MEASURES: Likelihood of recommending cesarean delivery. RESULTS: There were 1486
      clinicians who completed the survey. Clinicians were categorized based on answers
      to clinical vignettes. Having had lawsuits and daily worry of suits were
      associated with higher likelihood of recommending cesarean, compared to those
      without lawsuits (17.2 versus 11.3%, respectively; p = 0.008) as was frequent
      worry of lawsuits (every day, 20.3% more likely; every week/month, 12.3%; few
      times a year/never, 11.4%, p < 0.001). CONCLUSION: Obstetric malpractice lawsuit
      and frequent worry about lawsuit are associated with higher propensity of
      recommending cesarean delivery in common obstetric settings.

PMID- 24460459
TI  - Impact of organ transplantation in heart, lung and liver recipients: assessment
      of positive life changes.
AB  - OBJECTIVE: The majority of psychological studies with organ transplant recipients
      have examined negative psychological effects. This study aimed to further
      investigate the positive effects of organ transplantation and to construct a
      specific measurement instrument. DESIGN: The initial pool of 14 items for the
      Positive Effects of Transplant Scale (PETS) was derived from organ recipient
      interviews. A cross-sectional postal study included 87 heart, 46 lung and 193
      liver transplant recipients. The PETS was subjected to principal components
      analysis (PCA) using varimax rotation, and associations with other measures
      investigated. MAIN OUTCOME MEASURES: PETS and an open-ended item about positive
      effects. RESULTS: Coding of the open-ended item revealed that the majority of
      recipients attributed positive life changes to the transplant experience. PCA of
      the PETS indicated three factors that accounted for 58.82% of the variance. The
      12-item questionnaire assesses improvements in: (1) life philosophy, (2)
      gratitude and (3) health. The total PETS scores exhibited adequate internal
      consistency and validity. DISCUSSION: Most transplant patients report positive
      psychological effects, which suggests this may be an understudied area. The
      initial development of an assessment tool provides researchers and clinicians a
      way to assess the degree and nature of these life changes.

PMID- 24460461
TI  - Thiamin function, metabolism, uptake, and transport.
AB  - Vitamins are crucial components in the diet of animals and many other living
      organisms. One of these essential nutrients, thiamin, is known to be involved in
      several cell functions, including energy metabolism and the degradation of sugars
      and carbon skeletons. Other roles that are connected to this vitamin are neuronal
      communication, immune system activation, signaling and maintenance processes in
      cells and tissues, and cell-membrane dynamics. Because of the key functions of
      thiamin, uptake and transport through the body are crucial. Its uptake route is
      relatively complex, encompassing a variety of protein families, including the
      solute carrier anion transporters, the alkaline phosphatase transport system, and
      the human extraneuronal monoamine transporter family, some of which are
      multispecific proteins. There are two known structures of protein (subunits)
      involved in thiamin uptake in prokaryotes. Binding of thiamin to these proteins
      is strongly guided by electrostatic interactions. The lack of structural
      information about thiamin binding proteins for higher organisms remains a
      bottleneck for understanding the uptake process of thiamin in atomic detail. This
      review includes recent data on thiamin metabolism, related deficiencies and
      pathologies, and the latest findings on thiamin binding transporters. 

PMID- 24460464
TI  - An example of exceptional practice effects in the verbal domain.
AB  - XY, a 20-year-old mnemonist (current world ranking within the top 50) was tested
      with standard neuropsychological tests. XY recalled all words on all trials on
      the Rey Auditory Verbal Learning Test (RAVLT, 15 words) and scored above the
      99.9th percentile on the Wechsler Memory Scales R, Logical Memory (WLM, 2 short
      stories, 25 units per story, 50 units total). XY had not been previously tested
      with neuropsychological tests, but had trained memory techniques for
      approximately 8 years. We suggest that training on similar tasks resulted in
      substantial practice effects in the verbal memory domain, with no measurable
      transfer effects to the visual domain. In addition to previous findings, we
      present a practice effect on RAVLT and WLM exceeding previously documented test
      retest effects by 2-3 standard deviations. 

PMID- 24460465
TI  - Risk factors for hypothermia in EMS-treated burn patients.
AB  - OBJECTIVE: Hypothermia has been associated with increased mortality in burn
      patients. We sought to characterize the body temperature of burn patients
      transported directly to a burn center by emergency medical services (EMS)
      personnel and identify the factors independently associated with hypothermia.
      METHODS: We utilized prospective data collected by a statewide trauma registry to
      carry out a nested case-control study of burn patients transported by EMS
      directly to an accredited burn center between 2000 and 2011. Temperature at
      hospital admission <=36.5 degrees C was defined as hypothermia. We utilized
      registry data abstracted from prehospital care reports and hospital records in
      building a multivariable regression model to identify the factors associated with
      hypothermia. RESULTS: Forty-two percent of the sample was hypothermic. Burns of
      20-39% total body surface area (TBSA) (OR 1.44; 1.17-1.79) and >=40% TBSA (OR
      2.39; 1.57-3.64) were associated with hypothermia. Hypothermia was also
      associated with age > 60 (OR 1.50; 1.30-1.74), polytrauma (OR 1.58; 1.19-2.09),
      prehospital Glasgow Coma Scale <8 (OR 2.01; 1.46-2.78), and extrication (OR 1.49;
      1.30-1.71). Hypothermia was also more common in the winter months (OR 1.54; 1.33
      1.79) and less prevalent in patients weighing over 90 kg (OR 0.63; 0.46-0.88).
      CONCLUSIONS: A substantial proportion of burn patients demonstrate hypothermia at
      hospital arrival. Risk factors for hypothermia are readily identifiable by
      prehospital providers. Maintenance of normothermia should be stressed during
      prehospital care.

PMID- 24460467
TI  - A novel association between cytotoxin-associated gene A (CagA) positive strain of
      Helicobacter pylori and unexplained recurrent early pregnancy loss.
AB  - OBJECTIVE: To assess whether or not there is an association between the cytotoxin
      associated gene A (CagA)-positive strain of Helicobacter (H.) pylori and
      unexplained recurrent early pregnancy loss (REPL). METHODS: A case control study
      was conducted in a tertiary care maternity centre during a one-year period.
      Ninety-six women with first trimester unexplained REPL admitted for surgical or
      medical termination of pregnancy were included in the study group (group 1),
      along with 96 women who suffered a first trimester missed abortion but had no
      history of REPL and who were included in the control group (group 2). Sera from
      all these women were collected for detection of the CagA line of IgG type of H.
      pylori using an immunoblotting assay. The main outcome measure was the
      association between the CagA-positive strain of H. pylori and unexplained REPL.
      RESULTS: A significantly greater proportion of women were seropositive for the
      CagA- H. pylori strain in group 1 than in group 2 (71 [74%] vs. 51 [53%],
      respectively; p = 0.003). CONCLUSION: The CagA-positive strain of H. pylori seems
      to be significantly more prevalent among women with unexplained REPL when
      compared to women with a single missed abortion.

PMID- 24460466
TI  - Atopic dermatitis and risk of ischemic stroke: a nationwide population-based
      study.
AB  - BACKGROUND: Epidemiological studies have shown a strong association between
      systemic inflammatory diseases, particularly allergic diseases, and
      cardiovascular diseases. However, the relationship between atopic dermatitis (AD)
      and ischemic stroke remains unclear. METHOD: The study identified 20,323 AD
      patients and 20,323 comorbidity-matched subjects between 2005 and 2008. The two
      cohorts were followed until 31 December 2009. Ischemic stroke and other
      cardiovascular events were determined. RESULTS: During the follow-up period, 301
      (1.48%) patients in the AD cohort and 228 (1.12%) matched subjects experienced
      ischemic stroke. After multivariate adjustment, patients with AD had a 1.33-fold
      (95% confidence interval (CI), 1.12-1.59; P = 0.001) increased incidence of
      ischemic stroke. Adjusted hazard ratios for the risk of ischemic stroke in
      patients with mild, moderate, and severe AD were 1.20 (95% CI, 1.00-1.45; P =
      0.052), 1.64 (95% CI, 1.23-2.19; P = 0.001), and 1.71 (95% CI, 1.15-2.56; P =
      0.008), respectively. The log-rank test showed a higher cumulative incidence of
      ischemic stroke in the severe AD group than in the moderate and mild AD groups
      during the follow-up period (P < 0.001). CONCLUSIONS: AD may be an independent
      risk factor for ischemic stroke, and risk of ischemic stroke increases with AD
      severity.

PMID- 24460468
TI  - Microphthalmia in a case of Edward syndrome.
AB  - AIM: To present an infant of trisomy 18 (Edwards Syndrome) with unilateral
      microphthalmia. METHODS: A female infant who was born at 41 weeks of gestation
      had been diagnosed with Edwards Syndrome (ES). On ophthalmic examination,
      microphthalmia, microcornea, optic disc coloboma, and persistent hyaloid artery
      were determined in the left eye. In addition, abnormalities in the ears, hands,
      feet, and cardiovascular system were present. DISCUSSION: With this case report,
      we aimed to highlight the relationship between ocular disgenesis and chromosomal
      disorders and the importance of prenatal testing and genetic counseling for
      parents.

PMID- 24460470
TI  - Characterization of dissolved organic matter in municipal wastewater using
      fluorescence PARAFAC analysis and chromatography multi-excitation/emission scan:
      a comparative study.
AB  - Dissolved organic matter (DOM) in municipal wastewater was mainly characterized
      using high-performance liquid chromatography (HPLC) and size exclusion
      chromatography (HPSEC) with multi-excitation/emission fluorescence scan.
      Meanwhile, fluorescence excitation-emission-matrix combined with parallel factor
      analysis (EEM-PARAFAC) was also applied. Compared with chromatography
      fluorescence fingerprints, the EEM-PARAFAC model could not reflect the variety of
      DOM species with similar fluorescence but different physicochemical properties.
      The chromatography results showed that the protein-like species were variable
      among different municipal wastewater treatment plants, some of which are in
      combination with humic-like species; while there were two major humic-like
      species fractionated by hydrophilicity and molecular weight (MW), which are also
      the major contributors to UV absorbance at 254 nm. It was also identified that
      the relatively hydrophilic humic fractions were slightly larger than the
      relatively hydrophobic humic fractions. In all the investigated wastewater
      treatment plants, the relatively hydrophilic and larger MW humic fraction mainly
      contributed to the fluorescence intensity of humic-like EEM-PARAFAC components.
      As well as facilitating interpretations of EEM-PARAFAC components, the HPLC/HPSEC
      fluorescence fingerprints also contributed to a better understanding of
      fluorescent DOM species in municipal wastewater. 

PMID- 24460472
TI  - Eliminating first trimester markers: will replacing PAPP-A and betahCG miss women
      at risk for small for gestational age?
AB  - OBJECTIVE: Placental analytes are traditionally used for aneuploidy screening,
      although may be replaced by cell-free fetal DNA. Abnormal analytes also identify
      women at risk for small for gestational age (SGA). We sought to quantify the
      proportion of women at risk for SGA by low pregnancy-associated plasma protein-A
      (PAPP-A) or betahCG who would not otherwise be identified by maternal risk
      factors. METHODS: We studied first-trimester PAPPA-A and betahCG from 658 euploid
      singleton pregnancies from a prospective longitudinal cohort. Analytes were
      standardized for gestational age in multiples of the median (MoM). SGA was
      defined as birthweight z-score <=-1.28. Maternal risk factors included chronic
      hypertension, pre-gestational diabetes and age >=40. RESULTS: Mean GA was 38.8 +/
      1.9 weeks; 6.8% had a SGA infant. Low PAPP-A and betahCG were identified in 48
      (7.4%) and 9 (1.4%) of pregnancies, respectively, of whom 18.9% were SGA (OR 3.0,
      95% CI 1.4-6.3). 88% did not have risk factors for SGA. Among women with no risk
      factors, low PAPP-A was a significant predictor of SGA (OR 3.3, 95% CI 1.5-7.4).
      CONCLUSION: Most women with abnormal analytes did not have risk factors for SGA.
      Eliminating PAPP-A and betahCG may present missed opportunities to identify women
      at risk for SGA.

PMID- 24460473
TI  - In vitro-in vivo correlation of the effect of supersaturation on the intestinal
      absorption of BCS Class 2 drugs.
AB  - The aim of this study was to establish an in vitro method for evaluating the
      effect of supersaturation on oral absorption of poorly water-soluble drugs in
      vivo. Albendazole, dipyridamole, gefitinib, and ketoconazole were used as model
      drugs. Supersaturation of each drug was induced by diluting its stock solution by
      fasted state simulated intestinal fluid (FaSSIF) (solvent-shift method), then
      dissolution and precipitation profile of the drug was observed in vitro. The
      crystalline form of the precipitate was checked by differential scanning
      calorimetry (DSC). For comparison, control suspension was prepared by suspending
      a drug powder directly into FaSSIF (powder-suspending method). In vivo intestinal
      absorption of the drug was observed in rats by determined the plasma
      concentration after intraduodenal administration of drug suspensions. For all
      drugs, suspensions prepared by solvent-shift method showed significantly higher
      dissolved concentration in vitro than that prepared by powder-suspending method,
      clearly indicated the induction of supersaturation. DSC analysis revealed that
      crystalline form of the precipitate profoundly affects the extent and the
      duration of supersaturation. A rat in vivo study confirmed that the
      supersaturation of these drugs increased the fraction absorbed from the
      intestine, which corresponded well to the in vitro dissolution and precipitation
      profile of drugs except for ketoconazole. For ketoconazole, an in vivo absorption
      study was performed in rats pretreated with 1-aminobenzotriazole, a potent
      inhibitor of CYP mediated metabolism. CYP inhibition study suggested that the
      high luminal concentration of ketoconazole caused by supersaturation saturated
      the metabolic enzymes and further increased the systemic exposure of the absorbed
      drug. The additional effects of supersaturation on the absorption of ketoconazole
      are consistent with previous studies in humans under differing gastric pH
      conditions. In conclusion, effects of supersaturation on the intestinal
      absorption of poorly water-soluble drugs could be predicted from in vitro
      dissolution and a precipitation study. However if supersaturation affects the
      pharmacokinetic profiles of drugs, such as a first-pass metabolism, a combination
      with in vivo study should be required to evaluate its impact on oral
      bioavailability. 

PMID- 24460475
TI  - Preoperative pulmonary hypertension and its impact on survival after heart
      transplantation.
AB  - OBJECTIVES: Pulmonary hypertension (PH) due to left heart disease may impair
      outcome after heart transplantation (HT). To evaluate to what extent previous,
      and present, haemodynamic criteria discriminate the impact of pre-operative-PH on
      survival, we characterized the PH in our HT-patients according to ESC's
      guidelines, ISHLT's summary statement and ISHLT's relative contraindications and
      criteria for early risk of death after HT. DESIGN: Records from the 215 HT
      patients in Lund during 1988-2010 were reviewed. Subsequent analysis included
      adults (n = 94) evaluated with right-heart-catheterization at our lab, at rest
      before HT. End of follow-up was 30th of June 2012. RESULTS: Survival (mean, n)
      did not differ (p = ns) for the 94 HT-patients; without (13.0 years, n = 28) or
      with (13.9 years, n = 66) PH, passive (13.8 years, n = 50) or reactive (12.2
      years, n = 13) post-capillary-PH, "modified" passive (13.1 years, n = 40), mixed
      (16.6 years, n = 23), "modified" reactive (12.6 years, n = 7) or non-reactive
      (12.2 years, n = 8) post-capillary-PH; or for ISHLT's relative contraindications
      (12.0 years, n = 22) or increased risk of right-heart-failure and early death
      (16.5 years, n = 23) after HT. CONCLUSIONS: As previous and present haemodynamic
      criteria did not sufficiently discriminate the impact of pre-operative-PH for
      survival after HT at our centre, larger multi-centre studies are encouraged to
      redefine criteria that may influence outcome.

PMID- 24460477
TI  - Cortisol reactivity in the laboratory predicts ineffectual attentional control in
      daily life.
AB  - OBJECTIVE: The objective was to examine an executive control difficulty
      perspective on individual differences in cortisol reactivity using a daily
      protocol. DESIGN: Fifty participants competed a laboratory stressor task and
      individual differences in cortisol reactivity were quantified. MAIN OUTCOME
      MEASURES: Daily attentional control, conflicting thoughts, error reactivity,
      worry and mindfulness were assessed. RESULTS: The findings support the idea that
      as cortisol responses to stress get larger (as an individual difference),
      attentional control ceases to function as it should in terms of variables that
      should predict (mindfulness) and follow from (e.g. worry) it. CONCLUSION: The
      findings support the idea that individual differences in cortisol reactivity can
      be conceptualised in terms of ineffectual attentional control.

PMID- 24460479
TI  - Toward a molecular dynamics force field for simulations of 40% trifluoroethanol
      water.
AB  - Various computational models of trifluoroethanol (TFE) and water have been
      explored with the goal of finding a system for molecular dynamics (MD)
      simulations that reliably predict properties of 40% TFE-water (v/v) and can be
      used in studies of peptide-solvent nuclear cross-relaxation. Models derived by
      modification of TFE parameters developed by Fioroni et al. (J. Phys. Chem. B
      2000, 104, 12347), in combination with either TIP4P-Ew or TIP5P-E water, were
      most successful. Simulations of 40% TFE-TIP4P-Ew water evidenced separation of
      the system into large TFE-rich and water-rich domains. With TIP5P-E water,
      simulations showed aggregation of each solvent component into small clusters.
      Nuclear spin dipolar interactions between solvent fluorines and the methyl
      hydrogens of acetate ion dissolved in 40% TFE-water were calculated. The cross
      relaxation parameter sigmaHF reckoned for the TFE-TIP5P-E system agreed with
      experiment while the value calculated using the TFE-TIP4P-Ew system was too low.
      While the TFE-TIP5P-E model of 40% TFE-water leads to good predictions of the
      system density, translational diffusion coefficients, and a solvent-solute cross
      relaxation parameter, this model performs poorly in predicting the enthalpy of
      mixing. Preliminary studies of 20% TFE-water and 50% TFE-water suggest that the
      model will perform with the same characteristics for mixtures that have
      compositions near 40% TFE-water. 

PMID- 24460480
TI  - Coordinating role of His216 in MgATP binding and cleavage in pyruvate
      carboxylase.
AB  - His216 is a well-conserved residue in pyruvate carboxylases and, on the basis of
      structures of the enzyme, appears to have a role in the binding of MgATP, forming
      an interaction with the 3'-hydroxyl group of the ribose ring. Mutation of this
      residue to asparagine results in a 9-fold increase in the Km for MgATP in its
      steady-state cleavage in the absence of pyruvate and a 3-fold increase in the Km
      for MgADP in its steady-state phosphorylation by carbamoyl phosphate. However,
      from single-turnover experiments of MgATP cleavage, the Kd of the enzyme.MgATP
      complex is essentially the same in the wild-type enzyme and H216N. Direct stopped
      flow measurements of nucleotide binding and release using the fluorescent
      analogue FTP support these observations. However, the first-order rate constant
      for MgATP cleavage in the single-turnover experiments in H216N is only 0.75% of
      that for the wild-type enzyme, and thus, the MgATP cleavage step is rate-limiting
      in the steady state for H216N but not for the wild-type enzyme. Close examination
      of the structure of the enzyme suggested that His216 may also interact with
      Glu218, which in turn interacts with Glu305 to form a proton relay system
      involved in the deprotonation of bicarbonate. Single-turnover MgATP cleavage
      experiments with mutations of these two residues resulted in kinetic parameters
      similar to those observed in H216N. We suggest that the primary role of His216 is
      to coordinate the binding of MgATP and the deprotonation of bicarbonate in the
      reaction to form the putative carboxyphosphate intermediate by participation in a
      proton relay system involving Glu218 and Glu305. 

PMID- 24460481
TI  - Predictors of nontransport of older fallers who receive ambulance care.
AB  - OBJECTIVES: To identify patient, clinical, and operational factors associated
      with nontransport of older people who have fallen and received ambulance care;
      and to develop a nontransport prediction tool that could be utilized during the
      dispatch process to rationalize allocation of emergency ambulance resources.
      METHODS: The study was a planned subanalysis using data collected during a
      prospective observational cohort study of nonconsecutive emergency responses to
      older people aged 65 years or more who had fallen between October 1, 2010 and
      June 30, 2011. The data consisted of routinely collected ambulance dispatch and
      clinical records, combined with prospectively collected fall-specific
      information. Missing data were managed using multiple imputation. Multivariate
      logistic regression modeling was undertaken to identify predictors of
      nontransport. Results are described for original and imputated data sets,
      presented as odds ratios (OR) with 95%CI (confidence interval). Receiver
      operating curve (ROC) statistics were generated, with model discrimination
      determined by the area under the curve (AUC). RESULTS: There were 1,484 cases
      eligible for this subanalysis of which 419 (28.2%) were recorded as nontransport.
      Multivariate regression including dispatch and clinical variables identified a 6
      item final model. Younger age group, nonurgent response priority, and presence of
      a personal alarm were predictors of nontransport, along with clinical variables,
      including normal vital signs, absence of injury, and unchanged functional status
      post-fall. The AUC was 0.88 (95% CI 0.86-0.90; p < 0.0001) (imputed data AUC 0.86
      (95% CI 0.84-0.88)). Multivariate modeling of dispatch variables only identified
      a 3-item final model, which included response nonurgent response priority,
      younger age, and the presence of a personal alarm. The AUC was 0.68 (95% CI 0.64
      0.71; p < 0.0001) (imputed data AUC 0.69 (95% CI 0.66-0.72)). CONCLUSION: In this
      population of confirmed older fallers attended to by paramedics, determination of
      the prehospital transport outcome is greatly influenced by on-scene findings
      resulting from paramedic assessment. The presence of new pain, abnormal
      physiology, and altered function post-fall were strongly associated with
      increased odds of transport. Conversely the presence of a personal alarm and
      allocation of a nonurgent dispatch priority increased the odds of nontransport.
      Accurate discrimination between older fallers who were and were not transported
      using dispatch data only was not possible.

PMID- 24460482
TI  - Abolition of lifelong specific phobia: a novel therapeutic consequence of left
      mesial temporal lobectomy.
AB  - Numerous imaging studies have confirmed the amygdala as prominent within a neural
      network mediating specific phobia, including arachnophobia. We report the case of
      a patient in whom arachnophobia was abolished after left temporal mesial
      lobectomy, with unchanged fear responses to other stimuli. The phenomenon of
      abolition of specific phobia after amygdala removal has not, to our knowledge,
      been previously reported. 

PMID- 24460484
TI  - Color Doppler Imaging of the Orbital Vessels in Ankylosing Spondylitis.
AB  - PURPOSE: To analyze the hemodynamic features of orbital blood flow velocities
      using Doppler ultrasonography in ankylosing spondiylitis (AS) patients, as well
      as to compare these results with those of healthy controls. METHODS: 33 AS
      patients and 32 healthy controls were consecutively included in the study groups.
      The same radiologist performed ocular blood flow measurements. Peak systolic
      velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were
      measured in the central retinal artery (CRA), posterior ciliary arteries (PCAs),
      and ophthalmic artery (OA). Resistive index was used to assess arterial
      resistance; it was automatically calculated as RI [(PSV-EDV)/PSV]. RESULTS: There
      were no significant differences in the PSV, EDV, and RI of the OA, CRA, and PCAs
      between AS patients and controls. CONCLUSION: This result suggests no possible
      contributory role of vascular structures in formation of uveitis in AS. We
      believe that our preliminary results need to be complemented with further
      studies, particularly including AS patients with uveitis and rheumatic diseases
      with other ocular involvement.

PMID- 24460483
TI  - Current and emerging drug treatments for binge eating disorder.
AB  - INTRODUCTION: This study evaluated controlled treatment studies of
      pharmacotherapy for binge eating disorder (BED). AREAS COVERED: The primary focus
      of the review was on Phase II and III controlled trials testing medications for
      BED. A total of 46 studies were considered and 26 were reviewed in detail. BED
      outcomes included binge eating remission, binge eating frequency, associated
      eating disorder psychopathology, associated depression and weight loss. EXPERT
      OPINION: Data from controlled trials suggest that certain medications are
      superior to placebo for stopping binge eating and for producing faster reductions
      in binge eating, and - to varying degrees - for reducing associated eating
      disorder psychopathology, depression and weight loss over the short term. Almost
      no data exist regarding longer-term effects of medication for BED. Except for
      topiramate, which reduces both binge eating and weight, weight loss is minimal
      with medications tested for BED. Psychological interventions and the combination
      of medication with psychological interventions produce binge eating outcomes that
      are superior to medication-only approaches. Combining medications with
      psychological interventions does not significantly enhance binge eating outcomes,
      although the addition of certain medications enhances weight losses achieved with
      cognitive-behavioral therapy and behavioral weight loss, albeit modestly.

PMID- 24460486
TI  - More accurate neuronavigation data provided by biomechanical modeling instead of
      rigid registration.
AB  - It is possible to improve neuronavigation during image-guided surgery by warping
      the high-quality preoperative brain images so that they correspond with the
      current intraoperative configuration of the brain. In this paper, the accuracy of
      registration results obtained using comprehensive biomechanical models is
      compared with the accuracy of rigid registration, the technology currently
      available to patients. This comparison allows investigation into whether
      biomechanical modeling provides good-quality image data for neuronavigation for a
      larger proportion of patients than rigid registration. Preoperative images for 33
      neurosurgery cases were warped onto their respective intraoperative
      configurations using both the biomechanics-based method and rigid registration.
      The Hausdorff distance-based evaluation process, which measures the difference
      between images, was used to quantify the performance of both registration
      methods. A statistical test for difference in proportions was conducted to
      evaluate the null hypothesis that the proportion of patients for whom improved
      neuronavigation can be achieved is the same for rigid and biomechanics-based
      registration. The null hypothesis was confidently rejected (p < 10(-4)). Even the
      modified hypothesis that fewer than 25% of patients would benefit from the use of
      biomechanics-based registration was rejected at a significance level of 5% (p =
      0.02). The biomechanics-based method proved particularly effective in cases
      demonstrating large craniotomy-induced brain deformations. The outcome of this
      analysis suggests that nonlinear biomechanics-based methods are beneficial to a
      large proportion of patients and can be considered for use in the operating
      theater as a possible means of improving neuronavigation and surgical outcomes.

PMID- 24460487
TI  - Radiosurgery for Spetzler-Martin Grade III arteriovenous malformations.
AB  - OBJECT: Intracranial arteriovenous malformations (AVMs) are most commonly
      classified based on their Spetzler-Martin grades. Due to the composition of the
      Spetzler-Martin grading scale, Grade III AVMs are the most heterogeneous,
      comprising 4 distinct lesion subtypes. The management of this class of AVMs and
      the optimal treatment approach when intervention is indicated remain
      controversial. The authors report their experience with radiosurgery for the
      treatment of Grade III AVMs in a large cohort of patients. METHODS: All patients
      with Spetzler-Martin Grade III AVMs treated with radiosurgery at the University
      of Virginia over the 20-year span from 1989 to 2009 were identified. Patients who
      had less than 2 years of radiological follow-up and did not have evidence of
      complete obliteration during that period were excluded from the study, leaving
      398 cases for analysis. The median patient age at treatment was 31 years. The
      most common presenting symptoms were hemorrhage (59%), seizure (20%), and
      headache (10%). The median AVM volume was 2.8 cm(3), and the median prescription
      dose was 20 Gy. The median radiological and clinical follow-up intervals were 54
      and 68 months, respectively. Univariate and multivariate Cox proportional hazards
      and logistic regression analysis were used to identify factors associated with
      obliteration, postradiosurgery radiation-induced changes (RIC), and favorable
      outcome. RESULTS: Complete AVM obliteration was observed in 69% of Grade III AVM
      cases at a median time of 46 months after radiosurgery. The actuarial
      obliteration rates at 3 and 5 years were 38% and 60%, respectively. The
      obliteration rate was higher in ruptured AVMs than in unruptured ones (p <
      0.001). Additionally, the obliteration rate for Grade III AVMs with small size (<
      3 cm diameter), deep venous drainage, and location in eloquent cortex was higher
      than for the other subtypes (p < 0.001). Preradiosurgery AVM rupture (p = 0.016),
      no preradiosurgery embolization (p = 0.003), increased prescription dose (p <
      0.001), fewer isocenters (p = 0.006), and a single draining vein (p = 0.018) were
      independent predictors of obliteration. The annual risk of postradiosurgery
      hemorrhage during the latency period was 1.7%. Two patients (0.5%) died of
      hemorrhage during the radiosurgical latency period. The rates of symptomatic and
      permanent RIC were 12% and 4%, respectively. Absence of preradiosurgery AVM
      rupture (p < 0.001) and presence of a single draining vein (p < 0.001) were
      independent predictors of RIC. Favorable outcome was observed in 63% of patients.
      Independent predictors of favorable outcome were no preradiosurgery hemorrhage (p
      = 0.014), increased prescription dose (p < 0.001), fewer isocenters (p = 0.014),
      deep location (p = 0.014), single draining vein (p = 0.001), and lower Virginia
      radiosurgery AVM scale score (p = 0.016). CONCLUSIONS: Radiosurgery for Spetzler
      Martin Grade III AVMs yields relatively high rates of obliteration with a low
      rate of adverse procedural events. Small and ruptured lesions are more likely to
      become obliterated after radiosurgery than large and unruptured ones.

PMID- 24460488
TI  - Methodology and reporting of meta-analyses in the neurosurgical literature.
AB  - OBJECT: Neurosurgeons are inundated with vast amounts of new clinical research on
      a daily basis, making it difficult and time-consuming to keep up with the latest
      literature. Meta-analysis is an extension of a systematic review that employs
      statistical techniques to pool the data from the literature in order to calculate
      a cumulative effect size. This is done to answer a clearly defined a priori
      question. Despite their increasing popularity in the neurosurgery literature,
      meta-analyses have not been scrutinized in terms of reporting and methodology.
      METHODS: The authors performed a literature search using PubMed/MEDLINE to locate
      all meta-analyses that have been published in the JNS Publishing Group journals
      (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of
      Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Accepted
      checklists for reporting (PRISMA) and methodology (AMSTAR) were applied to each
      meta-analysis, and the number of items within each checklist that were
      satisfactorily fulfilled was recorded. The authors sought to answer 4 specific
      questions: Are meta-analyses improving 1) with time; 2) when the study met their
      definition of a meta-analysis; 3) when clinicians collaborated with a potential
      expert in meta-analysis; and 4) when the meta-analysis was the only focus of the
      paper? RESULTS: Seventy-two meta-analyses were published in the JNS Publishing
      Group journals and Neurosurgery between 1990 and 2012. The number of published
      meta-analyses has increased dramatically in the last several years. The most
      common topics were vascular, and most were based on observational studies. Only
      11 papers were prepared using an established checklist. The average AMSTAR and
      PRISMA scores (proportion of items satisfactorily fulfilled divided by the total
      number of eligible items in the respective instrument) were 31% and 55%,
      respectively. Major deficiencies were identified, including the lack of a
      comprehensive search strategy, study selection and data extraction, assessment of
      heterogeneity, publication bias, and study quality. Almost one-third of the
      papers did not meet our basic definition of a meta-analysis. The quality of
      reporting and methodology was better 1) when the study met our definition of a
      meta-analysis; 2) when one or more of the authors had experience or expertise in
      conducting a meta-analysis; 3) when the meta-analysis was not conducted alongside
      an evaluation of the authors' own data; and 4) in more recent studies.
      CONCLUSIONS: Reporting and methodology of meta-analyses in the neurosurgery
      literature is excessively variable and overall poor. As these papers are being
      published with increasing frequency, neurosurgical journals need to adopt a clear
      definition of a meta-analysis and insist that they be created using checklists
      for both reporting and methodology. Standardization will ensure high-quality
      publications.

PMID- 24460489
TI  - Endovascular treatment of fusiform cerebral aneurysms with the Pipeline
      Embolization Device.
AB  - OBJECT: Despite advances in surgical and endovascular techniques, fusiform
      aneurysms remain a therapeutic challenge. Introduction of flow-diverting stents
      has revolutionized the treatment of aneurysms with wide necks and of complex
      morphology. The authors report their experience with the endovascular treatment
      of fusiform aneurysms using the Pipeline Embolization Device. METHODS: A
      retrospective review of 146 patients with cerebral aneurysms treated with the
      Pipeline Embolization Device between June 2011 and January 2013 was performed.
      Twenty-four patients were identified as having fusiform aneurysms. Twenty-four
      aneurysms in these 24 patients were treated. The mean patient age was 59 years.
      There were 9 men and 15 women. Angiographic and clinical data (including the
      modified Rankin Scale [mRS] score) were recorded at the time of treatment and at
      follow-up. The aneurysms were located in the internal carotid artery in 8
      patients (33.3%), middle cerebral artery in 8 patients (33.3%), anterior cerebral
      artery in 1 patient (4%), and vertebrobasilar circulation in 7 patients (29%).
      The aneurysms were smaller than 10 mm in 3 patients, 10-25 mm in 16 patients, and
      larger than 25 mm in 5 patients. The mean largest dimension diameter was 18 mm.
      RESULTS: Stent deployment was successful in all cases. The minor procedural
      morbidity was 4% (1 case). Morbidity and mortality related to aneurysm treatment
      were 4.2% and 4.2%, respectively. The mean mRS scores preoperatively and at
      clinical follow-up (median 6.0 months, mean 6.9 months) were 0.71 and 1.2,
      respectively (91.7% presented with an mRS score of 2 or better, and 79.2% had an
      mRS score of 2 or better at the 6.0-month follow-up). At clinical follow-up,
      82.6% of patients were stable or had improved, 13.0% worsened, and 4.2% had died.
      Twenty-two (91.7%) of 24 patients had follow-up angiography available (mean
      follow-up time 6.3 months); 59% had excellent angiographic results (> 95% or
      complete occlusion), 31.8% had complete aneurysm occlusion, 27.3% had greater
      than 95% aneurysm occlusion, 18.2% had a moderate decrease in size (50%-95%),
      4.5% had a minimal decrease in size (< 50%), 13.6% had not changed, and 4.5% had
      an increase in size. CONCLUSIONS: This series demonstrates that endovascular
      treatment of fusiform cerebral aneurysms with flow diversion was a safe and
      effective treatment. Procedural complications were low. Long-term morbidity and
      mortality rates were acceptable given the complex nature of these lesions.

PMID- 24460490
TI  - Suppression of neurocan and enhancement of axonal density in rats after treatment
      of traumatic brain injury with scaffolds impregnated with bone marrow stromal
      cells.
AB  - OBJECT: Neurocan is a major form of growth-inhibitory molecule (growth-IM) that
      suppresses axonal regeneration after neural injury. Bone marrow stromal cells
      (MSCs) have been shown to inhibit neurocan expression in vitro and in animal
      models of cerebral ischemia. Therefore, the present study was designed to
      investigate the effects of treatment of MSCs impregnated with collagen scaffolds
      on neurocan expression after traumatic brain injury (TBI). METHODS: Adult male
      Wistar rats were injured with controlled cortical impact and treated with saline,
      human MSCs (hMSCs) (3 * 10(6)) alone, or hMSCs (3 * 10(6)) impregnated into
      collagen scaffolds (scaffold + hMSCs) transplanted into the lesion cavity 7 days
      after TBI (20 rats per group). Rats were sacrificed 14 days after TBI, and brain
      tissues were harvested for immunohistochemical studies, Western blot analyses,
      laser capture microdissections, and quantitative real-time reverse transcriptase
      polymerase chain reaction (qRT-PCR) to evaluate neurocan protein and gene
      expressions after various treatments. RESULTS: Animals treated with scaffold +
      hMSCs after TBI showed increased axonal and synaptic densities compared with the
      other groups. Scaffold + hMSC treatment was associated with reduced TBI-induced
      neurocan protein expression and upregulated growth-associated protein 43 (GAP-43)
      and synaptophysin expression in the lesion boundary zone. In addition, animals in
      the scaffold + hMSC group had decreased neurocan transcription in reactive
      astrocytes after TBI. Reduction of neurocan expression was significantly greater
      in the scaffold + hMSC group than in the group treated with hMSCs alone.
      CONCLUSIONS: The results of this study show that transplanting hMSCs with
      scaffolds enhances the effect of hMSCs on axonal plasticity in TBI rats. This
      enhanced axonal plasticity may partially be attributed to the downregulation of
      neurocan expression by hMSC treatment after injury.

PMID- 24460491
TI  - Methodology and reporting of meta-analyses in the neurosurgical literature.

PMID- 24460493
TI  - Gamma Knife radiosurgery and arteriovenous malformations.

PMID- 24460492
TI  - Reduced ethanol consumption by alcohol-preferring (P) rats following
      pharmacological silencing and deep brain stimulation of the nucleus accumbens
      shell.
AB  - OBJECT: There is increasing interest in deep brain stimulation (DBS) for the
      treatment of addiction. Initial testing must be conducted in animals, and the
      alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism.
      This study is composed of 2 experiments designed to examine the effects of 1)
      pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on
      the consumption of alcohol by P rats. METHODS: In the first experiment, the
      effects of reversible inactivation of the AcbSh were investigated by
      administering intracranial injections of gamma-aminobutyric acid (GABA) agonists.
      Bilateral microinjections of drug were administered to the AcbSh in P rats (8-10
      rats/group), after which the animals were placed in operant chambers containing 2
      levers--one used to administer water and the other to administer 15% EtOH--to
      examine the acquisition and maintenance of oral EtOH self-administration. In the
      second experiment, a DBS electrode was placed in each P rat's left AcbSh. The
      animals then received 100 or 200 MUA (3-4 rats/group) of DBS to examine the
      effect on daily consumption of oral EtOH in a free-access paradigm. RESULTS: In
      the first experiment, pharmacological silencing of the AcbSh with GABA agonists
      did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH
      consumption by 55% in chronically drinking rats. Similarly, in the second
      experiment, 200 MUA of DBS consistently reduced EtOH intake by 47% in chronically
      drinking rats. The amount of EtOH consumption returned to baseline levels
      following termination of therapy in both experiments. CONCLUSIONS:
      Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic
      EtOH use had been established in rodents. The AcbSh is a neuroanatomical
      substrate for the reinforcing effects of alcohol and may be a target for surgical
      intervention in cases of alcoholism.

PMID- 24460496
TI  - Continuing education as the public relations arm.

PMID- 24460495
TI  - Rate of control of LDL cholesterol and incident hypertension requiring
      antihypertensive treatment in hypercholesterolemic subjects in daily clinical
      practice.
AB  - INTRODUCTION: Preliminary evidence suggests that hypercholesterolemia is
      associated to an increased risk to develop hypertension. We aimed at evaluating
      the association between low-density lipoprotein cholesterol (LDL-C) level and
      incidence of new onset of hypertension in a large population sample. MATERIALS
      AND METHODS: A population-based cohort of 20,074 subjects with at least one LDL-C
      measurement between July 2006 and June 2007 and free of antihypertensive
      treatment (AHT) at baseline was followed from the LDL-C date until death or 31
      December 2009. RESULTS: During the follow-up, 10.7% of patients with LDL-C < 130
      mg/dL, 13.2% of patients with LDL-C between 130 and 159 mg/dL, 12.2% of patients
      with LDL-C between 160 and 189 mg/dL, and 13.9% of patients with LDL-C >= 190
      mg/dL had new-onset hypertension requiring the initiation of AHT. Compared with
      the LDL-C < 130 mg/dL group, the hazard ratio (HR) of initiation of AHT increased
      among those with LDL-C level between 130 and 159 mg/dL (HR 1.23; 95% CI: 1.08
      1.40), those with LDL-C level between 160 and 189 mg/dL (HR 1.24; 95% CI: 1.01
      1.51), and those with LDL-C >= 190 mg/dL (HR 1.45; 95% CI: 1.11-1.89).
      CONCLUSION: A better control of cholesterolemia seems to be associated to a lower
      incidence of new-onset of hypertension requiring AHT in a large cohort of general
      population.

PMID- 24460498
TI  - Heterologous microarray analysis of transcriptome alterations in Mus spretus mice
      living in an industrial settlement.
AB  - This work demonstrates the successful application of a commercial oligonucleotide
      microarray containing Mus musculus whole-genome probes to assess the biological
      effects of an industrial settlement on inhabitant Mus spretus mice. The
      transcriptomes of animals in the industrial settlement contrasted with those of
      specimens collected from a nearby protected ecosystem. Proteins encoded by the
      differentially expressed genes were broadly categorized into six main functional
      classes. Immune-associated genes were mostly induced and related to innate and
      acquired immunity and inflammation. Genes sorted into the stress-response
      category were mainly related to oxidative-stress tolerance and biotransformation.
      Metabolism-associated genes were mostly repressed and related to lipid metabolic
      pathways; these included genes that encoded 11 of the 20 cholesterol biosynthetic
      pathway enzymes. Crosstalk between members of different functional categories was
      also revealed, including the repression of serine-protease genes and the
      induction of protease-inhibitor genes to control the inflammatory response.
      Absolute quantification of selected transcripts was performed via RT-PCR to
      verify the microarray results and assess interindividual variability. Microarray
      data were further validated by immunoblotting and by cholesterol and protein
      thiol oxidation level determinations. Reported data provide a broad impression of
      the biological consequences of residing in an industrial area. 

PMID- 24460500
TI  - Effect of injectable medroxyprogesterone acetate and etonogestrel implants on
      GABA-A and serotonin receptors in white and gray matter of the brain:
      experimental study in rats.
AB  - The aim of this study was to evaluate the time-dependent effect of progesterone
      only contraceptives on the brain and to obtain an improved understanding of mood
      disorders experienced under this medication. A total of 66 Wistar albino rats
      were divided into three groups: etonogestrel (ENG) implant (group 1, n = 30);
      depot medroxyprogesterone acetate (MPA)-injectable (group 2, n = 30); and control
      (group 3, n = 6) groups. Groups 1 and 2 were each divided into five subgroups,
      which were examined every 10 d for up to 50 d after medication administration, to
      evaluate its time-dependent effect. There was no difference in terms of gamma
      aminobutyric acid (GABA) and serotonin immunohistochemical staining in white and
      gray matter among the subgroups of group 1. In group 2, there was a significant
      decrease in serotonin receptor staining intensity in white and gray matter on day
      50, when compared to the control group (p = 0.041). When the subgroups of group 2
      were compared, there was a significant decrease in serotonin receptor staining
      intensity in white and gray matter on days 40 and 50 when compared to day 10. In
      conclusion, we showed that ENG and MPA have no effect on apoptosis and GABA-A
      receptors in the brain. We also showed that MPA has time-dependent effects on
      serotonin receptors, which may be a possible mechanism involved in mood disorders
      during long-term usage of injectable progesterone-only contraceptives.

PMID- 24460502
TI  - Nonalcoholic fatty liver disease and metabolic syndrome in postmenopausal women.
AB  - Nonalcoholic fatty liver disease (NAFLD) is considered the most common cause of
      chronic liver disease in the Western countries. NAFLD includes a spectrum ranging
      from a simple steatosis to a nonalcoholic steatohepatitis (NASH) which is defined
      by the presence of inflammatory infiltrate, cellular necrosis, hepatocyte
      ballooning, and fibrosis and cirrhosis that can eventually develop into
      hepatocellular carcinoma. Studies emphasize the role of insulin resistance,
      oxidative stress, pro-inflammatory cytokines, adipokines in the development and
      progression of NAFLD. It seems to be independently associated with type II
      diabetes mellitus, increased triglycerides, decreased HDL-cholesterol, abdominal
      obesity and insulin resistance. These findings are in accordance with the
      criteria used in the diagnosis of metabolic syndrome (MetS). Here, we will
      discuss the current knowledge on the epidemiology, pathophysiology and diagnosis
      of NAFLD and the association of metabolic syndrome in postmenopausal women.

PMID- 24460501
TI  - Cushing's syndrome in pregnancy: a case report and mini review of the literature.
AB  - Adrenal diseases in pregnant women are diagnosed relatively rarely. The main
      cause of hypercortisolemia during pregnancy is Cushing's syndrome related to
      adrenal adenoma. It is important to diagnose Cushing's syndrome in pregnant women
      because it can lead to significant maternal and foetal complications and
      morbidity. However, due to physiological endocrine changes and symptoms in
      pregnant women the diagnosis of this disorder can be a challenge. One current
      case describes a 38-year-old pregnant woman with hypertension, oedema and an
      adrenal tumour. At the beginning, Conn syndrome was suspected, but after careful
      analysis Cushing's syndrome (with an adenoma of the right adrenal gland) was
      diagnosed. After delivery and 5 weeks of pharmacological treatment the patient
      underwent right side adrenalectomy by laparoscopy.

PMID- 24460503
TI  - Manganese(III)-mediated selective diphenylphosphinoyl radical reaction of 1,4
      diaryl-1-butynes for the synthesis of 2-phosphinoylated 3,4-dihydronaphathalenes.
AB  - A diphenylphosphinoyl radical-initiated sequential reaction of 1,4-diaryl-1
      butynes and analogues is developed for the synthesis of 2-phosphinoylated 3,4
      dihydronaphathalenes and related compounds. 

PMID- 24460504
TI  - Interfacial structural role of pH-shifting processed pea protein in the oxidative
      stability of oil/water emulsions.
AB  - Understanding the behavior of protein surfactants at the oil-water interface is
      essential to the design of physicochemically stable emulsions. The objective of
      the study was to investigate the steric role of an interfacial membrane made of
      structurally modified pea protein with alkaline pH treatment (APP) in the
      oxidative stability of oil-in-water emulsions. Confocal laser scanning microscopy
      depicted more uniform and smaller oil droplets that had a reduced tendency to
      coalesce for emulsions prepared with APP than with native pea protein (NPP).
      Correspondingly, the APP emulsions were less prone to oxidation (malonaldehyde,
      peroxide) during storage. Similarly, cryo-transmission electron microscopy
      revealed more uniform air pockets with smoother undersurface that were surrounded
      by partially coalesced emulsions in whipped creams prepared with APP than with
      NPP. The improved interfacial properties and steric hindrance played a crucial
      role in the inhibition of oxidation in emulsions by alkaline pH-modified pea
      protein. 

PMID- 24460505
TI  - Catheter ablation for ventricular tachycardia in ischaemic heart disease; acute
      success and long-term outcome.
AB  - OBJECTIVES: We conducted a study to assess the acute procedural success and the
      long-term effect of radiofrequency ablation (RFA) for ventricular tachycardia
      (VT) in patients with ischaemic heart disease. DESIGN: We included 90 patients
      with ischaemic heart disease treated with RFA for VT in our institution. Data
      were obtained from patient files, and implantable cardioverter-defibrillator
      (ICD) discharges were recorded from in-house and remote follow-up data.
      Recurrence of VT during follow-up was noted as date of first ICD therapy for VT
      or first recurrence of symptomatic VT. RESULTS: After the initial RFA procedure
      no VT was inducible in 42 patients (47%), non-clinical VT was inducible in 21
      patients (23%), and the clinical VT was still inducible in 14 patients (16%). The
      procedural success was indefinable in 13 patients (14%). After a median follow-up
      of 33 months after the latest RFA, 38 patients (42%) stayed free from recurrent
      VT. The number of ICD shocks/year was significantly reduced from median 1.1
      (interquartile range: 0.3-2.8) to 0 (0-0.4) (p < 0.0001). CONCLUSIONS: Procedural
      success rate as well as long-term freedom from recurrent VT is modest after RFA
      for VT in ischaemic heart disease. However, ICD discharges are significantly
      reduced after RFA, and a considerable proportion of patients remain free from
      recurrent VT during the long-term follow-up.

PMID- 24460506
TI  - Automated optimization of water-water interaction parameters for a coarse-grained
      model.
AB  - We have developed an automated parameter optimization software framework (ParOpt)
      that implements the Nelder-Mead simplex algorithm and applied it to a coarse
      grained polarizable water model. The model employs a tabulated, modified Morse
      potential with decoupled short- and long-range interactions incorporating four
      water molecules per interaction site. Polarizability is introduced by the
      addition of a harmonic angle term defined among three charged points within each
      bead. The target function for parameter optimization was based on the
      experimental density, surface tension, electric field permittivity, and diffusion
      coefficient. The model was validated by comparison of statistical quantities with
      experimental observation. We found very good performance of the optimization
      procedure and good agreement of the model with experiment. 

PMID- 24460509
TI  - Comparison of video, optical, and direct laryngoscopy by experienced tactical
      paramedics.
AB  - OBJECTIVES: While optical and video laryngoscopy have been studied in the
      emergency department, the operating room, and the routine prehospital setting,
      their efficacy in the tactical environment--in which operator safety is as
      important as intubation success--has not been evaluated. This study compared
      direct laryngoscopes to optical (AirTraq) and video (King Vision) laryngoscopes
      in a simulated tactical setting. METHODS: This prospective institutional review
      board-approved simulation study evaluated each of the laryngoscopes in the hands
      of seven experienced tactical paramedics. After a one-hour training session, each
      tactical paramedic used each of the laryngoscopes, in a random order, on each of
      four different airway manikins. A tactical environment was simulated using
      auditory and visual immersion, and the intubations occurred on the ground with
      the paramedics in full tactical gear. Outcomes included time to successful
      ventilation, first-pass success rate, Cormack-Lehane grade, and intubator head
      height during the intubation. Statistical analysis included chi-squared and
      Wilcoxon rank sum tests, and multivariate logistic regression was performed to
      determine contributing factors to outcomes with significant variation. RESULTS: A
      total of 84 intubations were performed by seven tactical paramedics. While there
      were no significant differences in time to successful ventilation or first-pass
      success rate, the optical and video laryngoscopes had significantly better
      Cormack-Lehane grades, defined as grade I or II (100% for both compared to
      85.7%), while direct laryngoscopy resulted in significantly less maximum vertical
      exposure of the intubator (51.82 cm compared to AirTraq's 56.64 cm and King
      Vision's 56.13 cm). CONCLUSION: Video and optical laryngoscopes can be used
      successfully by experienced tactical paramedics in a simulated tactical setting.
      The King Vision and AirTraq resulted in improved Cormack-Lehane glottic views but
      similar times to ventilation and first-pass success compared to direct
      laryngoscopy. Intubator head height was lower with direct laryngoscopy.
      Clarifying the role of optical and video laryngoscopes in a tactical environment,
      especially in the hands of less experienced intubators, requires further
      research.

PMID- 24460510
TI  - Implications of pharmacogenetics for the therapeutic use of antiepileptic drugs.
AB  - INTRODUCTION: Epilepsy is a chronic neurological disease manifesting as recurrent
      seizures. Despite the availability of numerous antiepileptic drugs (AEDs), one
      third of the patients are not responsive to treatment. Such inter-individual
      variability in the response to AEDs may be partly explained by genetic
      differences. This review summarizes the pharmacogenetics (PGx) of AEDs. In
      addition, a model-based approach is presented that enables the integration of PGx
      data with other relevant sources of variability, such as demographic
      characteristics and co-medications. AREAS COVERED: A comprehensive overview is
      provided of the data available in the literature on the evidence for correlations
      between genetic mutations and pharmacokinetic (PK) and/or pharmacodynamics (PD)
      of AEDs. This information is then used in an integrated manner in the second
      part, where PGx differences are parameterized as covariates in PK and PKPD
      models. EXPERT OPINION: Polymorphisms are profuse in the PK and PD of AEDs.
      However, understanding of their clinical implication remains limited due to the
      lack of methodologies that discriminate the contribution of other sources of
      variability in CNS exposure to drugs. A model-based approach, in which other
      intrinsic (e.g., demographic covariates) and extrinsic (e.g., drug-drug
      interactions) factors are evaluated concurrently is needed to ensure optimization
      and individualization of treatment in epileptic patients.

PMID- 24460511
TI  - Network of hydrogen bonds near the oxygen-evolving Mn(4)CaO(5) cluster of
      photosystem II probed with FTIR difference spectroscopy.
AB  - We previously provided experimental evidence that an extensive network of
      hydrogen bonds exists near the oxygen-evolving Mn4CaO5 cluster in photosystem II
      and that elements of this network form part of a dominant proton-egress pathway
      leading from the Mn4CaO5 cluster to the thylakoid lumen. The evidence was based
      on (i) the elimination of the same nu(C?O) mode of a protonated carboxylate group
      in the S2-minus-S1 FTIR difference spectrum of wild-type PSII core complexes from
      the cyanobacterium Synechocystis sp. PCC 6803 by the mutations D1-E65A, D2-E312A,
      and D1-E329Q and (ii) the substantial decrease in the efficiency of the S3 to S0
      transition caused by the mutations D1-D61A, D1-E65A, and D2-E312A. The eliminated
      nu(C?O) mode corresponds to an unidentified carboxylate group whose pKa value
      decreases in response to the increased charge that develops on the Mn4CaO5
      cluster during the S1 to S2 transition. In the current study, we have extended
      our work to include the nu(C?O) regions of other Sn+1-minus-Sn FTIR difference
      spectra and to additional mutations of residues inferred to participate in
      networks of hydrogen bonds near the Mn4CaO5 cluster or leading from the Mn4CaO5
      cluster to the thylakoid lumen. Our data suggest that a different carboxylate
      group has its pKa value increased during the S2 to S3 transition and that a third
      carboxylate group experiences a change in its environment during the S0 to S1
      transition. The pKa values that shift during the S1 to S2 and S2 to S3
      transitions appear to be restored during the S3 to S0 transition. The D1-R334A
      mutation decreases or eliminates the same nu(C?O) modes from the S2-minus-S1 and
      S3-minus-S2 spectra as mutations D1-E65A, D2-E312A, and D1-E329Q and
      substantially decreases the efficiency of the S3 to S0 transition. We conclude
      that D1-R334 participates in the same dominant proton-egress pathway that was
      identified in our previous study. The D1-Q165E mutation leaves the nu(C?O) region
      of the S2-minus-S1 FTIR difference spectrum intact, but it eliminates a mode from
      this region of the S3-minus-S2 spectrum. We conclude that D1-Q165 participates in
      an extensive network of hydrogen bonds that that extends across the Mn4CaO5
      cluster to the D1-E65/D2-E312 dyad and that includes D1-E329 and several water
      molecules including the W2 and W3 water ligands of the Mn4CaO5 cluster's dangling
      MnA4 and Ca ions, respectively. The D2-E307Q, D2-D308N, D2-E310Q, and D2-E323Q
      mutations alter the nu(C?O) regions of none of the FTIR difference spectra. We
      conclude that these four residues are located far from the three unidentified
      carboxylate groups that give rise to the nu(C?O) features observed in the FTIR
      difference spectra. 

PMID- 24460512
TI  - Effects of acute and chronic psychological stress on platelet aggregation in
      mice.
AB  - Although psychological stress has long been known to alter cardiovascular
      function, there have been few studies on the effect of psychological stress on
      platelets, which play a pivotal role in cardiovascular disease. In the present
      study, we investigated the effects of acute and chronic psychological stress on
      the aggregation of platelets and platelet cytosolic free calcium concentration
      ([Ca(2+)]i). Mice were subjected to both transportation stress (exposure to novel
      environment, psychological stress) and restraint stress (psychological stress)
      for 2 h (acute stress) or 3 weeks (2 h/day) (chronic stress). In addition,
      adrenalectomized mice were subjected to similar chronic stress (both
      transportation and restraint stress for 3 weeks). The aggregation of platelets
      from mice and [Ca(2+)]i was determined by light transmission assay and fura-2
      fluorescence assay, respectively. Although acute stress had no effect on agonist
      induced platelet aggregation, chronic stress enhanced the ability of the platelet
      agonists thrombin and ADP to stimulate platelet aggregation. However, chronic
      stress failed to enhance agonist-induced increase in [Ca(2+)]i. Adrenalectomy
      blocked chronic stress-induced enhancement of platelet aggregation. These results
      suggest that chronic, but not acute, psychological stress enhances agonist
      stimulated platelet aggregation independently of [Ca(2+)]i increase, and the
      enhancement may be mediated by stress hormones secreted from the adrenal glands.

PMID- 24460514
TI  - Brain structure alterations associated with weight changes in young females with
      anorexia nervosa: a case series.
AB  - Structural brain changes associated with starvation and clinical measurements
      were explored in four females with anorexia nervosa with different clinical
      course, at baseline and 1-year follow-up, after receiving intensive inpatient
      treatment at a specialized eating disorder unit. Global volume alterations were
      associated with weight changes. Regional volume alterations were also associated
      with weight changes, with the largest changes occurring in the nucleus accumbens,
      amygdala, pallidum, and putamen. Largest changes in cortical thickness occurred
      in the frontal and temporal lobes. The results are preliminary; however, they
      show that fluctuations in weight are associated with brain volume alterations,
      especially gray matter. We suggest that these parts of the brain are vulnerable
      to starvation and malnutrition, and could be a part of the pathophysiology of AN.

PMID- 24460515
TI  - Dry Eye Syndrome in Non-Exophthalmic Graves' Disease.
AB  - BACKGROUND: The present study aims to assess qualitative and quantitative
      characteristics of tear film and corneal related impairment and to evaluate the
      quality of life in a cohort of non-exophthalmic Graves' disease (GD) patients.
      METHODS: The series comprised 50 eyes from 25 newly diagnosed GD patients with no
      proptosis. As control group, 56 eyes of 28 thyroid disease-free subjects were
      enrolled. RESULTS: The results of Schirmer I and II, break-up time, and Oxford
      scheme showed a significant difference between GD and controls. By ocular surface
      disease index (OSDI) questionnaire, eleven (44%) GD patients had normal ocular
      surface, while two (8%) had mild, four (16%) had moderate, and eight (32%) had
      severe dry eye. The mean score of the OSDI in the GD group was significantly (p <
      0.001) higher with respect to the control group. CONCLUSIONS: This study shows
      that the tear film and cornea are damaged in newly non-exophthalmic GD subjects.

PMID- 24460516
TI  - Lipid profile changes in patients with rheumatic diseases receiving a treatment
      with TNF-alpha blockers: a meta-analysis of prospective studies.
AB  - BACKGROUND: Some studies showed an anti-atherogenic effect of TNF-alpha blockers
      on lipid profile, but these data have been challenged. OBJECTIVE: To perform a
      meta-analysis on lipid profile changes induced by TNF-alpha blocker treatment.
      METHODS: Prospective studies on rheumatic patients receiving TNF-alpha blockers
      and providing before-and-after treatment values of triglycerides (TGs), total
      cholesterol (TC), HDL-cholesterol (HDLc), LDL-cholesterol (LDLc), and atherogenic
      index (AI) were included. Standardized mean differences (SMD) in lipid profile
      were analyzed at short-term (2-12 weeks), middle-term (13-24 weeks), and long
      term (25-52 weeks) assessments. RESULTS: Thirty articles (1707 patients) were
      included. TNF-alpha blockers determined an increase in TC at short-term, middle
      term, and long-term assessments (SMD: 0.20 mmol/L [95% CI: 0.04, 0.35]; SMD: 0.27
      mmol/L [95% CI: 0.08, 0.46]; SMD: 0.22 mmol/L [95% CI: 0.01, 0.43]). HDLc
      increased only at the short-term assessment (SMD: 0.19 mmol/L [95% CI: 0.10,
      0.28]), and TGs achieved a significant increase at the long-term assessment (SMD:
      0.19 mmol/L [95% CI: 0.04, 0.34]). LDLc and AI were not affected by TNF-alpha
      blocker treatment. CONCLUSIONS: Slight but significant increases in TC occurred
      without any significant change in LDLc and AI. Changes in HDLc and TGs were not
      consistent among the different time point assessments. These quantitative changes
      in lipid profile do not seem to be able to explain cardiovascular risk
      improvement reported in patients receiving TNF-alpha blockers. Further studies on
      other mechanisms are needed to address this issue.

PMID- 24460517
TI  - Homogenization and lipase treatment of milk and resulting methyl ketone
      generation in blue cheese.
AB  - A specific range of methyl ketones contribute to the distinctive flavor of
      traditional blue cheeses. These ketones are metabolites of lipid metabolism by
      Penicillium mold added to cheese for this purpose. Two processes, namely, the
      homogenization of milk fat and the addition of exogenous lipase enzymes, are
      traditionally applied measures to control the formation of methyl ketones in blue
      cheese. There exists little scientific validation of the actual effects of these
      treatments on methyl ketone development. The present study evaluated the effects
      of milk fat homogenization and lipase treatments on methyl ketone and free fatty
      acid development using sensory methods and the comparison of selected volatile
      quantities using gas chromatography. Initial work was conducted using a blue
      cheese system model; subsequent work was conducted with manufactured blue cheese.
      In general, there were modest effects of homogenization and lipase treatments on
      free fatty acid (FFA) and methyl ketone concentrations in blue cheese. Blue
      cheese treatments involving Penicillium roqueforti lipase with homogenized milk
      yielded higher FFA and methyl ketone levels, for example, a ~20-fold increase for
      hexanoic acid and a 3-fold increase in 2-pentanone. 

PMID- 24460519
TI  - FeCl3 catalyzed regioselective C-alkylation of indolylnitroalkenes with amino
      group substituted arenes.
AB  - An efficient FeCl3 catalyzed protocol for the synthesis of amino functionalized
      indolylnitroalkanes from easily available precursor indolylnitroalkenes and
      substituted amines has been developed. Regioselective C-alkylation in the
      presence of free amino substituted arenes occurred. The scope of this methodology
      shows good functional group tolerance, and further, this protocol was used to
      prepare indolylquinoline derivatives. 

PMID- 24460518
TI  - Scaling up evidence-based practices for children and families in New York State:
      toward evidence-based policies on implementation for state mental health systems.
AB  - Dissemination of innovations is widely considered the sine qua non for system
      improvement. At least two dozen states are rolling out evidence-based mental
      health practices targeted at children and families using trainings,
      consultations, webinars, and learning collaboratives to improve quality and
      outcomes. In New York State (NYS) a group of researchers, policymakers,
      providers, and family support specialists have worked in partnership since 2002
      to redesign and evaluate the children's mental health system. Five system
      strategies driven by empirically based practices and organized within a state
      supported infrastructure have been used in the child and family service system
      with more than 2,000 providers: (a) business practices, (b) use of health
      information technologies in quality improvement, (c) specific clinical
      interventions targeted at common childhood disorders, (d) parent activation, and
      (e) quality indicator development. The NYS system has provided a laboratory for
      naturalistic experiments. We describe these initiatives, key findings and
      challenges, lessons learned for scaling, and implications for creating evidence
      based implementation policies in state systems. 

PMID- 24460521
TI  - Recognition and treatment of exertional heat illness at a marathon race.
AB  - Exertional heat illness is rarely encountered by individual EMS providers but can
      be common in certain settings and events. The notion that significantly altered
      mental status must accompany elevated core temperature in heat illness may delay
      recognition and treatment. We report on a series of marathon and half-marathon
      runners who suffered exertional heat illness during a marathon race in relatively
      mild conditions. Altered mental status was not uniformly present. All patients
      were treated in the finish line medical tent and responded well to cooling. More
      than half were discharged from the medical tent without being transported to the
      hospital. This case series demonstrates that many runners respond to early
      identification and treatment of exertional heat illness. Significant preparation
      is required by the medical providers to handle the rapid influx of patients at
      the conclusion of the event.

PMID- 24460522
TI  - Temperature dependence of hydrophobic hydration dynamics: from retardation to
      acceleration.
AB  - The perturbation induced by a hydrophobic solute on water dynamics is essential
      in many biochemical processes, but its mechanism and magnitude are still debated.
      A stringent test of the different proposed pictures is provided by recent NMR
      measurements by Qvist and Halle (J. Am. Chem. Soc. 2008, 130, 10345-10353) which
      showed that, unexpectedly, the perturbation changes in a non-monotonic fashion
      when the solution is cooled below room temperature. Here we perform and analyze
      molecular dynamics simulations of a small paradigm amphiphilic solute,
      trimethylamine N-oxide (TMAO), in dilute aqueous solutions over the 218-350 K
      temperature range. We first show that our simulations properly reproduce the non
      monotonic temperature dependence. We then develop a model which combines our
      previously suggested entropic excluded-volume effect with a perturbation factor
      arising from the difference between local structural fluctuations in the shell
      and the bulk. Our model provides a detailed molecular understanding of the
      hydrophobic perturbation over the full temperature range investigated. It shows
      that the excluded-volume factor brings a dominant temperature-independent
      contribution to the perturbation at all temperatures, and provides a very good
      approximation at room temperature. The non-monotonic temperature dependence of
      the perturbation is shown to arise from the structural factor and mostly from
      relative shifts between the shell and bulk distributions of local structures,
      whose amplitude remains very small compared to the widths of those distributions.

PMID- 24460523
TI  - Effect of simulated extracorporeal circulation and glyceryl-tri-nitrate on
      leukocyte activation.
AB  - OBJECTIVES: During extracorporeal circulation (ECC), a mechanical pump and an
      oxygenator replace the functions of the heart and lungs. The aim of this study is
      to test the effect of the nitric oxide donor glyceryl-tri-nitrate on activation
      markers of the innate immune system during simulated ECC. DESIGN: Whole blood
      concentrations of selected leukocyte adhesion molecules, complement system
      components and myeloperoxidase (MPO) were measured in an in vitro system of
      simulated ECC. RESULTS: Simulated ECC stimulated the expression of monocyte LPS
      receptor CD14 and C3b-receptor CD35. Glyceryl-tri-nitrate significantly reduced
      the expression of leukocyte Fcgamma receptor CD32 over time, compared to control.
      Simulated ECC increased the concentrations of MPO, terminal complement complex,
      and complement component C3a. Addition of glyceryl-tri-nitrate did not
      significantly affect these changes. CONCLUSIONS: Simulated ECC induces the
      increased expression of some leukocyte markers. Glyceryl-tri-nitrate addition
      significantly reduces the expression of some leukocyte activation markers.

PMID- 24460524
TI  - Cutaneous cryptococcosis in Hodgkin lymphoma.

PMID- 24460525
TI  - Hodgkin lymphoma-associated paraneoplastic cerebellar degeneration on FDG-PET/CT.

PMID- 24460526
TI  - Myocardial iron overload in thalassaemia major. How early to check?
AB  - The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR)
      T2* screening in thalassaemia major (TM) is still uncertain. To clarify this
      point, we evaluated the prevalence of myocardial iron overload (MIO), function
      and fibrosis by CMR in TM patients younger than 10 years. We retrospectively
      selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia
      network. MIO was measured by T2* multislice multiecho technique. Biventricular
      function parameters were evaluated by cine images. To detect myocardial fibrosis,
      late gadolinium enhancement images were acquired. Patients' age ranged from 4.2
      to 9.7 years. All scans were performed without sedation. Nine patients showed no
      MIO, 22 patients had heterogeneous MIO with a T2* global value >=20 ms; two
      patients had heterogeneous MIO with a T2* global value <20 ms and two patients
      showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients
      with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction
      and the iron transfused was <35 g in all cases. Cardiac iron loading can occur
      much earlier than previously described. The first cardiac T2* assessment should
      be performed as early as feasible without sedation, especially if chelation is
      started late or if poor compliance is suspected.

PMID- 24460527
TI  - Resources in colleges and universities.

PMID- 24460528
TI  - The conservation nexus: valuing interdependent water and energy savings in
      Arizona.
AB  - Water and energy resources are intrinsically linked, yet they are managed
      separately--even in the water-scarce American southwest. This study develops a
      spatially explicit model of water-energy interdependencies in Arizona and
      assesses the potential for cobeneficial conservation programs. The interdependent
      benefits of investments in eight conservation strategies are assessed within the
      context of legislated renewable energy portfolio and energy efficiency standards.
      The cobenefits of conservation are found to be significant. Water conservation
      policies have the potential to reduce statewide electricity demand by 0.82-3.1%,
      satisfying 4.1-16% of the state's mandated energy-efficiency standard. Adoption
      of energy-efficiency measures and renewable generation portfolios can reduce
      nonagricultural water demand by 1.9-15%. These conservation cobenefits are
      typically not included in conservation plans or benefit-cost analyses. Many
      cobenefits offer negative costs of saved water and energy, indicating that these
      measures provide water and energy savings at no net cost. Because ranges of costs
      and savings for water-energy conservation measures are somewhat uncertain, future
      studies should investigate the cobenefits of individual conservation strategies
      in detail. Although this study focuses on Arizona, the analysis can be extended
      elsewhere as renewable portfolio and energy efficiency standards become more
      common nationally and internationally.

PMID- 24460529
TI  - Finite size effects on textured surfaces: recovering contact angles from
      vagarious drop edges.
AB  - A clue to understand wetting hysteresis on superhydrophobic surfaces is the
      relation between receding contact angle and surface textures. When the surface
      textures are large, there is a significant distribution of local contact angles
      around the drop. As seen from the cross section, the apparent contact angle
      oscillates as the triple line recedes. Our experiments demonstrate that the
      origin of these oscillations is a finite size effect. Combining side and bottom
      views of the drop, we take into account the 3D conformation of the surface near
      the edge to evaluate an intrinsic contact angle from the oscillations of the
      apparent contact angle. We find that for drops receding on axisymmetric textures
      the intrinsic receding contact angle is the minimum value of the oscillation
      while for a square lattice it is the maximum. 

PMID- 24460530
TI  - DNP-enhanced MAS NMR of bovine serum albumin sediments and solutions.
AB  - Protein sedimentation sans cryoprotection is a new approach to magic angle
      spinning (MAS) and dynamic nuclear polarization (DNP) nuclear magnetic resonance
      (NMR) spectroscopy of proteins. It increases the sensitivity of the experiments
      by a factor of ~4.5 in comparison to the conventional DNP sample preparation and
      circumvents intense background signals from the cryoprotectant. In this paper, we
      investigate sedimented samples and concentrated frozen solutions of natural
      abundance bovine serum albumin (BSA) in the absence of a glycerol-based
      cryoprotectant. We observe DNP signal enhancements of epsilon ~ 66 at 140 GHz in
      a BSA pellet sedimented from an aqueous solution containing the biradical
      polarizing agent TOTAPOL and compare this with samples prepared using the
      conventional protocol (i.e., dissolution of BSA in a glycerol/water
      cryoprotecting mixture). The dependence of DNP parameters on the radical
      concentration points to the presence of an interaction between TOTAPOL and BSA,
      so much so that a frozen solution sans cryoprotectant still gives epsilon ~ 50.
      We have studied the interaction of BSA with another biradical, SPIROPOL, that is
      more rigid than TOTAPOL and has been reported to give higher enhancements.
      SPIROPOL was also found to interact with BSA, and to give epsilon ~ 26 close to
      its maximum achievable concentration. Under the same conditions, TOTAPOL gives
      epsilon ~ 31, suggesting a lesser affinity of BSA for SPIROPOL with respect to
      TOTAPOL. Altogether, these results demonstrate that DNP is feasible in self
      cryoprotecting samples. 

PMID- 24460531
TI  - Hope for children and families: targeting abusive parenting and the associated
      impairment of children.
AB  - The purpose of this study is to distill the "effective practice elements" from
      randomised controlled interventions (RCTs) to prevent the recurrence of abusive
      and neglectful parenting and the associated health and developmental impairment
      of children. The resulting elements would be used then to develop a step-by-step
      modular-systemic approach to intervention that is suitable to the needs of a
      variety of frontline practitioners in social care, health, and education. A
      series of 22 randomised RCTs were analysed using the distillation and matching
      approach to establish the presence of effective practice elements. The focus was
      physical and sexual abuse, victims and children, and young people as
      perpetrators; neglect including failure to thrive, emotional abuse (exposure to
      violence and mental health issues). The studies were analysed for effective
      practice elements, across different approaches matched to interventions focused
      on parenting, on children and young people, and on family/professional
      relationships. The proportion of practice elements utilised in each form of
      maltreatment was defined. The distillation process resulted in a total of 47
      practice elements present across all forms of maltreatment studied. An
      experienced group of practitioners from statutory and voluntary agencies ordered
      and integrated the most frequently utilised emerging elements into a series of
      step-by-step modules, which could fit the complex needs of families when
      maltreatment had occurred. The resulting manual, Hope for Children and Families,
      provides a "menu" of evidence-based, step-by-step modular interventions targeting
      the profile of abusive and neglectful parenting and associated impairments of
      children. To be effective for frontline practitioners, the manual will need to be
      delivered in a user-friendly format, training developed, and supervision and
      support provided. 

PMID- 24460533
TI  - Different outcomes for the MYB floral symmetry genes DIVARICATA and RADIALIS
      during the evolution of derived actinomorphy in Plantago.
AB  - The gene network that specifies flower shape in Antirrhinum majus (bilateral
      floral symmetry or zygomorphy) includes two MYB-class genes - RADIALIS (RAD) and
      DIVARICATA (DIV). RAD is involved in establishing the dorsal identity program and
      its role is to regulate the domain of activity of DIV (the ventral identity
      program) by restricting it to ventral regions of the flower. Plantago is in the
      same family as Antirrhinum but has small, radially symmetrical (actinomorphic)
      flowers derived from a zygomorphic ancestral state. Here we investigate the MYB
      class floral symmetry genes and the role they have played in the evolution of
      derived actinomorphy in Plantago lanceolata. A DIV ortholog (PlDIV) but no RAD
      ortholog was identified in P. lanceolata. PlDIV is expressed across all petals
      and stamens later in flower development, which is consistent with the loss of RAD
      gene function. PlDIV expression in anther sporogenous tissue also suggests that
      PlDIV was co-opted to regulate cell proliferation during the early stages of
      pollen development. These results indicate that evolution of derived actinomorphy
      in Plantago involved complete loss of dorsal gene function, resulting in
      expansion of the domain of expression of the ventral class of floral symmetry
      genes. 

PMID- 24460532
TI  - Does prolonged storage of red blood cells cause harm?
AB  - Red blood cells (RBCs) degrade progressively during the weeks of refrigerated
      storage. No universally accepted definition of 'fresh' or 'old' RBCs exists.
      While practices vary from country to country, preservative solutions permitting
      shelf life as long as 7 weeks have been licenced. Transfusion of stored RBCs,
      particularly those at the end of the approved shelf life, has been implicated in
      adverse clinical outcomes. The results of observational analyses, animal models
      and studies in volunteers have proved provocative, controversial and
      contradictory. A recently completed randomized controlled trial (RCT) in
      premature infants exemplifies the difficulties with moderately sized clinical
      studies. Several other RCTs are in progress. The effect of RBC storage may well
      vary according to the clinical setting. Resolution of the importance of the
      storage lesion may require large pragmatic clinical trials. In the meantime,
      institutions involved in blood collection and transfusion should explore
      strategies that assure blood availability, while limiting the use of the oldest
      RBCs currently approved by regulation. 

PMID- 24460534
TI  - Versatile roles of the chaperonin GroEL in microorganism-insect interactions.
AB  - The chaperonin 60 (Cpn60) is present in all three kingdoms of life and is one of
      the most conserved proteins in living organisms. The Escherichia coli Cpn60
      (GroEL) is the best studied representative of the huge Cpn60 family. It is an
      essential protein because in conjunction with the chaperonin 10 (Cpn10 or GroES)
      it forms a protein-folding machine required for correct folding of many proteins
      and for recycling of misfolded proteins. As many other chaperones, GroEL and
      GroES are also known as heat-shock proteins (HSPs), since heat stress leads to a
      strong induction of their expression, a measure to counteract the increase in
      misfolded proteins as a result of a high nonphysiological temperature. A large
      amount of literature is available which is dedicated to the elucidation of how
      protein folding is assisted by this molecular chaperone. However, apart from this
      primary task, additional so-called 'moonlighting' functions of GroEL proteins
      unrelated to their folding activity have emerged in the past years. In fact, it
      becomes apparent that GroEL proteins have diverse functions in particular in
      mutualistic and pathogenic microorganism-host interactions. In this brief review,
      we describe some of these recent findings focusing on the importance of GroEL for
      microorganism-insect interactions. 

PMID- 24460535
TI  - Strain-dependent differences for suppression of insulin-stimulated glucose uptake
      in skeletal and cardiac muscle by ethanol.
AB  - BACKGROUND: Chronic ethanol (EtOH) consumption impairs the ability of insulin to
      suppress hepatic glucose production in a strain-dependent manner, with hepatic
      insulin resistance being greater in Long-Evans (LE) than Sprague-Dawley (SD)
      rats. We assessed whether strain differences exist for whole-body and tissue
      glucose uptake under basal and insulin-stimulated conditions and whether they
      were associated with coordinate strain-dependent elevations in muscle cytokines.
      METHODS: Male rats (160 g) were provided the Lieber-DeCarli EtOH-containing (36%
      total energy) diet or pair-fed a control diet for 8 weeks. Rats were studied in
      the basal state or during a euglycemic hyperinsulinemic clamp, and whole-body
      glucose flux assessed using (3) H-glucose and in vivo tissue glucose uptake by
      (14) C-2-deoxyglucose. RESULTS: EtOH impaired whole-body insulin-mediated glucose
      uptake (IMGU) more in SD than LE rats. This difference was due to impaired IMGU
      by gastrocnemius and heart in EtOH-fed SD versus LE rats. However, decreased IMGU
      in adipose tissue (epididymal and perirenal) produced by EtOH was comparable
      between strains. EtOH-induced insulin resistance in muscle from SD rats was
      associated with reduced AKT and AS160 phosphorylation and plasma membrane
      localized GLUT4 protein as well as enhanced phosphorylation of c-Jun N-terminal
      kinase (JNK) and IRS-1 (S307), changes which were absent in muscle from LE rats.
      EtOH increased tumor necrosis factor alpha (TNFalpha) mRNA in gastrocnemius and
      fat under basal conditions in both SD and LE rats; however, hyperinsulinemia
      decreased TNFalpha in skeletal muscle from LE, but not SD rats. Interleukin (IL)
      6 mRNA in gastrocnemius was increased under basal conditions and increased
      further in response to insulin in SD rats, but no EtOH- or insulin-induced change
      was detected in muscle IL-6 of LE rats. CONCLUSIONS: These data indicate strain
      dependent differences in EtOH-induced IMGU in skeletal and cardiac muscle, but
      not fat, associated with sustained increases in TNFalpha and IL-6 mRNA and JNK
      activation and decreased plasma membrane GLUT4 in response to insulin.

PMID- 24460536
TI  - A cluster randomised controlled trial evaluating an incentive-based outdoor
      physical activity programme to increase outdoor time and prevent myopia in
      children.
AB  - PURPOSE: To evaluate an incentive-based intervention to increase time spent
      outdoors among children in a 9-month cluster randomised controlled trial.
      METHODS: Two hundred and eighty-five children aged 6-12 years of age were
      randomised to the intervention (n = 147) or control arm (n = 138) in the Family
      incentive trial (FIT). The FIT intervention comprised of targeted education on
      myopia and good eye care habits, structured weekend outdoor activities and
      incentives for children to increase their daily steps via pedometers. The main
      outcome measure was outdoor time, measured by the WHO questionnaire and a 1-week
      diary. RESULTS: Interim analysis at 6 months showed a significant increase in
      mean outdoor time per week in the intervention arm (14.75 h week(-1) ) compared
      to the control arm (12.40 h week(-1) ) as measured by the questionnaire (p =
      0.04). However, greater outdoor time was not statistically significant at the end
      of the trial (15.95 h week(-1) vs 14.34 h in the control group (p = 0.29).
      CONCLUSIONS: There was an increase in outdoor time for children in the incentive
      based physical activity outdoor program after 6 months but not at the end of the
      trial. Further larger school trials with better compliance with the intervention
      and longer duration could be conducted to evaluate clinical outcomes such as
      myopic shifts.

PMID- 24460538
TI  - In search of an effective treatment for recurrent mesangiocapillary
      glomerulonephritis in the renal allograft.
AB  - In patients with end-stage kidney disease (ESKD) secondary to mesangiocapillary
      glomerulonephritis (MCGN), recurrent disease post transplantation is a common
      cause of graft loss. We report a case of a 33-year-old female with ESKD due to
      idiopathic MCGN who developed recurrent disease in two consecutive renal
      allografts. Recurrent disease was diagnosed two months after receiving her
      primary transplant from a live related donor. Oral cyclophosphamide was initiated
      but discontinued after 10 months due to cystitis. This was followed by rapid
      deterioration in her renal function. Despite salvage therapy with rituximab, the
      graft was lost 2 years post transplantation. After 7 years on haemodialysis, the
      patient received a second graft from a deceased donor. Recurrent MCGN was once
      again diagnosed one year post transplantation. She was treated with plasma
      exchange and rituximab. Despite ongoing nephrotic range proteinuria, her graft
      function remained stable 2 years post transplantation. The optimal therapy for
      recurrent MCGN is unknown at this stage. It is hoped that a better understanding
      of its pathogenesis will enable the development of more effective and targeted
      therapies. 

PMID- 24460537
TI  - miR444a has multiple functions in the rice nitrate-signaling pathway.
AB  - Nitrate (NO3-) is a key signaling molecule in plant metabolism and development,
      in addition to its role as a nutrient. It has been shown previously in
      Arabidopsis that ANR1, a MADS-box transcription factor, is a major component in
      the NO3--signaling pathway that triggers lateral root growth and that miR444,
      which is specific to monocots, targets four genes that are homologous to ANR1 in
      rice. Here, we show that miR444a plays multiple roles in the rice NO3--signaling
      pathway - not only in root development, but also involving nitrate accumulation
      and even Pi -starvation responses. miR444a overexpression resulted in reduced
      rice lateral root elongation, but promoted rice primary and adventitious root
      growth, in a nitrate-dependent manner. In addition, overexpression of miR444a
      improved nitrate accumulation and expression of nitrate transporter genes under
      high nitrate concentration conditions, but reduced the remobilization of nitrate
      from old leaves to young leaves thus affecting the plant's ability to adapt to
      nitrogen-limitating conditions. Intriguingly, we found that Pi starvation
      strongly induced miR444 accumulation in rice roots and that overexpression of
      miR444a altered Pi -starvation-induced root architecture and enhanced Pi
      accumulation and expression of three Pi transporter genes. We further provide
      evidence that miR444a is involved in the interaction between the NO3--signaling
      and Pi -signaling pathways in rice. Taken together, our observations demonstrated
      that miR444a plays multiple roles in the rice NO3--signaling pathway in nitrate
      dependent root growth, nitrate accumulation and phosphate-starvation responses. 

PMID- 24460539
TI  - Dynamics of albumin synthetic response to intra-abdominal abscess in patients
      with gastrointestinal fistula.
AB  - BACKGROUND: Low serum albumin concentration is a predictor of failure of source
      control for intra-abdominal infection. However, data on dynamics of albumin
      synthesis in these patients and to what extent these changes contribute to
      hypoalbuminemia are relatively scarce. We investigated in a group of patients
      with gastrointestinal fistula the dynamic response of liver albumin synthesis to
      intra-abdominal abscess and how these related to hypoalbuminemia and circulating
      endocrine hormone profiles. METHODS: Eight gastrointestinal fistula patients
      scheduled to undergo percutaneous abscess sump drainage were enrolled
      prospectively to measure albumin synthesis rates at different stages of the
      inflammatory response (immediately after diagnosis and 7 d following sump
      drainage when clinical signs of intra-abdominal sepsis had been eradicated).
      Eight age-, sex-, and body mass index-matched intestinal fistula patients were
      studied as control patients. Consecutive arterial blood samples were drawn during
      a primed-constant infusion (priming dose: 4 micromol.kg(-1), infusion rate: 6
      micromol.kg(-1).min(-1)) to determine the incorporation rate of L-[ring-(2)H5]
      phenylalanine directly into plasma albumin using gas chromatography/mass
      spectrometry analysis. RESULTS: Patients suffering from intra-abdominal infection
      had reduced plasma albumin and total plasma protein concentrations, compared with
      control patients. Albumin fractional synthesis rates in patients with intra
      abdominal abscess were decreased, compared with those in the control group. When
      the source of infection was removed, albumin synthesis rates returned to control
      values, whereas albumin concentrations did not differ significantly from the
      corresponding concentrations in control subjects and patients with intra
      abdominal abscess. CONCLUSION: Despite nutritional intervention, albumin
      synthesis rate is decreased in intestinal fistula patients with intra-abdominal
      abscess; albumin synthesis returns to control values during convalescence.

PMID- 24460540
TI  - Differential structural status of the RNA counterpart of an undecamer quasi
      palindromic DNA sequence present in LCR of human beta-globin gene cluster.
AB  - Our previous work on structural polymorphism shown at a single nucleotide
      polymorphism (SNP) (A -> G) site located on HS4 region of locus control region
      (LCR) of beta-globin gene has established a hairpin -> duplex equilibrium
      corresponding to A -> B like DNA transition (Kaushik M, Kukreti, R., Grover, D.,
      Brahmachari, S.K. and Kukreti S. Nucleic Acids Res. 2003; Kaushik M, Kukreti S.
      Nucleic Acids Res. 2006). The G-allele of A -> G SNP has been shown to be
      significantly associated with the occurrence of beta-thalassemia. Considering the
      significance of this 11-nt long quasi-palindromic sequence [5'-TGGGG(G/A)CCCCA;
      HP(G/A)11] of beta-globin gene LCR, we further explored the differential behavior
      of the same DNA sequence with its RNA counterpart, using various biophysical and
      biochemical techniques. In contrast to its DNA counterpart exhibiting a A -> B
      structural transition and an equilibrium between duplex and hairpin forms, the
      studied RNA oligonucleotide sequence [5'-UGGGG(G/A)CCCCA; RHP(G/A)11] existed
      only in duplex form (A-conformation) and did not form hairpin. The single residue
      difference from A to G led to the unusual thermal stability of the RNA structure
      formed by the studied sequence. Since, naturally occurring mutations and various
      SNP sites may stabilize or destabilize the local DNA/RNA secondary structures,
      these structural transitions may affect the gene expression by a change in the
      protein-DNA recognition patterns.

PMID- 24460541
TI  - Native aortic valve endocarditis complicated by pseudoaneurysm of mitral-aortic
      intervalvular fibrosa.
AB  - Pseudoaneurysm of mitral-aortic intervalvular fibrosa (PA-MAIVF) is a rare
      complication of native aortic valve endocarditis. This region is a relatively
      avascular area and prone to infection during endocarditis and subsequent aneurysm
      formation. The rupture into the pericardial cavity and left atrium or aorta,
      systemic embolism, myocardial infarction secondary to left coronary compression,
      and sudden death are the reported complications. Herein, we present a 9-year-old
      boy who was diagnosed with bicuspid aortic valve endocarditis complicated by PA
      MAIVF, cerebral embolism, and hemorrhage. PA-MAIVF was visualized by both two-
      and three-dimensional transthoracic echocardiography and ruptured into
      pericardial space causing a fatal outcome. 

PMID- 24460542
TI  - Energy-optimised pharmacophore approach to identify potential hotspots during
      inhibition of Class II HDAC isoforms.
AB  - Histone deacetylases (HDACs) are conjugated enzymes that modulate chromatin
      architecture by deacetylating lysine residues on the histone tails leading to
      transcriptional repression. Pharmacological interventions of these enzymes with
      small molecule inhibitors called Histone deacetylase inhibitors (HDACi) have
      shown enhanced acetylation of the genome and are hence emerging as potential
      targets at the clinic. Type-specific inhibition of Class II HDACs has shown
      enhanced therapeutic benefits against developmental and neurodegenerative
      disorders. However, the structural identity of class-specific isoforms limits the
      potential of their inhibitors in precise targeting of their enzymes. Diverse
      strategies have been implemented to recognise the features in HDAC enzymes which
      may help in identifying isoform specificity factors. This work attempts a
      computational approach that combines in silico docking and energy-optimised
      pharmacophore (E-pharmacophore) mapping of 18 known HDAC inhibitors and has
      identified structural variations that regulate their interactions against the six
      Class II HDAC enzymes considered for the study. This combined approach
      establishes that inhibitors possessing higher number of aromatic rings in
      different structural regions might function as potent inhibitors, while
      inhibitors with scarce ring structures might point to compromised potency. This
      would aid the rationale for chemical optimisation and design of isoform selective
      HDAC inhibitors with enhanced affinity and therapeutic efficiency. 

PMID- 24460543
TI  - Two-dimensional tissue tracking: a novel echocardiographic technique to measure
      left atrial volume: comparison with biplane area length method and real time
      three-dimensional echocardiography.
AB  - Enlargement of the left atrium is an independent predictor of adverse
      cardiovascular outcomes, and an accurate, convenient imaging modality is
      necessary for clinical practice. The objectives of this study were to evaluate
      the feasibility of a novel imaging technique, two-dimensional tissue tracking
      (2DTT), for assessment of left atrial (LA) volume and function and to compare its
      correlation and agreement with biplane area length (AL) method and real time
      three-dimensional echocardiography (RT3DE). A total of 105 patients prospectively
      underwent 2DTT, AL and RT3DE. The LA volume index (LAVI) and emptying fraction
      were measured. In addition, intra- and inter-observer agreement were calculated
      by using the intraclass correlation coefficient. There were no significant
      differences in LAVI and emptying fraction measured by 2DTT in comparison with
      those made by AL or RT3DE, furthermore Bland-Altman analysis showed that 2DTT had
      significantly better agreement for LAVI and emptying fraction with AL and RT3DE.
      2DTT also exhibited smaller intra- and inter-observer variability as compared
      with AL or RT3DE. Furthermore, the time to measure LA volume and acquire time
      volume curve was significantly less by 2DTT than that by RT3DE (U = 49.00, P <
      0.001). These observations suggest that the 2DTT could provide valuable
      information which is consistent with the standard AL and RT3DE measurements for
      LAVI and function with potentially lower intra- and inter-observer variability.

PMID- 24460544
TI  - Attacking mechanism of hydroxyl radical to DNA base-pair: density functional
      study in vacuum and in water.
AB  - Recently, the influence of radiation on human body has been recognized as a
      serious problem. In particular, highly reactive hydroxyl radicals *OH produced by
      the radiation react with DNA, resulting in a great damage on its structure and
      electronic properties. It is thus important to investigate the reaction mechanism
      of *OH to DNA for elucidating the initial damage in DNA induced by the radiation.
      In the present study, we search for transition states (TS) of the reaction
      between G-C/A-T base-pair and [Formula: see text] in vacuum and in water, by the
      density functional theory (DFT) calculations. At first, we obtain the stable
      structures for the dehydrogenated G-C and A-T, in which the hydrogen atom of NH2
      group of G or A base is abstracted by [Formula: see text]. From the structures of
      the dehydrogenated as well as the natural base-pairs, the TS between these
      structures is searched for and the activation free energy (AFE) is estimated for
      the reaction. In vacuum, AFEs for the G-C and A-T are almost the same each other,
      while the stabilization energy by the reaction for G-C is about 4.9 kcal/mol
      larger than that for A-T, indicating that the population of the dehydrogenated G
      C is remarkably larger than that of the dehydrogenated A-T in vacuum. On the
      other hand, in water approximated by the continuum solvation model, the AFE for A
      T is 2.6 kcal/mol smaller than that for G-C, indicating that the reaction
      dehydrogenated by [Formula: see text] occurs more frequently for the solvated A-T
      base-pair than G-C.

PMID- 24460545
TI  - Coronary computed tomography angiography-based tricuspid annular plane systolic
      excursion: correlation with 2D echocardiography.
AB  - BACKGROUND: Right heart evaluation on coronary computed tomography angiography
      (CCTA) is underutilized due to nonopacification of the right heart chambers and
      poor endocardial resolution. We analyzed feasibility and reproducibility of right
      heart functional analysis by measuring CCTA-based tricuspid annular plane
      systolic excursion (CT-TAPSE) on ECG-gated CCTA and correlated the results with
      2D transthoracic echocardiography (TTE)-derived TAPSE (Echo-TAPSE). METHODS: CT
      TAPSE was measured on a total population of 41 patients who had CCTA and TTE
      performed within 6 months of each other. Two independent CCTA readers performed
      analysis on reformatted four-chamber view. Intra- and inter-observer variability
      analysis was performed on 16 randomly selected patients. Correlative (Spearman's
      R) and Bland-Altman analysis was used to assess the level of agreement between
      the 2 methods and to compare CT-TAPSE with Echo-TAPSE. RESULTS: CT-TAPSE measured
      by Readers 1 and 2 on 16 randomly selected patients, demonstrated excellent intra
      observer and inter-observer agreement, with very close correlation (R > 0.80 and
      2-tailed P-value of <0.001). When tested in the entire study population of 41
      patients, CT-TAPSE correlated closely with Echo-TAPSE (R = 0.738, P < 0.001).
      Bland-Altman analysis indicated that the 2 methods provided similar measures as
      majority of values lay within the 95% confidence limits. Based on abnormal Echo
      TAPSE cutoff value of <16 mm, CT-TAPSE identified impaired right ventricle (RV)
      function with sensitivity of 82% and specificity of 93%, respectively.
      CONCLUSION: We demonstrated feasibility and reproducibility of assessing TAPSE on
      coronary CTA. RV functional analysis utilizing CT-TAPSE is simple and
      reproducible methodology, and is in close agreement with Echo-TAPSE.

PMID- 24460546
TI  - Spirito-Maron echocardiographic score: a marker for morphological and
      physiological assessment of patients with hypertrophic cardiomyopathy.
AB  - AIMS: The heterogeneous distribution of hypertrophy in hypertrophic
      cardiomyopathy (HCM) limits the echocardiographic conventional measurements
      accuracy in the evaluation of left ventricular hypertrophy (LVH). The aim of this
      study was to assess the correlation of the echocardiographic Spirito-Maron score
      (SMS) with left ventricle (LV) mass quantification by cardiac magnetic resonance
      (CMR) and with LV diastolic function. METHODS AND RESULTS: Left ventricle
      diastolic function parameters, SMS, LV mass (American Society of Echocardiography
      formula), and maximal wall thickness (MWT) were evaluated by two-dimensional (2D)
      transthoracic echocardiography. The SMS was obtained by adding the MWT of 4 LV
      segments, at the mitral valve or papillary muscles short-axis views.
      Echocardiographic parameters of LVH, including SMS, were correlated with LV mass
      obtained by CMR and with E/e' ratio. We included 45 patients (60% male, mean age
      48 +/- 18 years), who underwent 2D echocardiography. Twenty-two of them performed
      a CMR study. A positive correlation was found between SMS and CMR LV mass (r =
      0.80; P < 0.001), whereas MWT (r = 0.62; P = 0.002) and the 2D LV mass (r = 0.60;
      P = 0.011) presented a lower correlation with CMR LV mass. The SMS was
      significantly correlated with E/e' ratio (r = 0.60; P = 0.007), whereas a
      nonsignificant correlation was found with MWT (r = 0.41; P = 0.081) and 2D LV
      mass (r = 0.22; P = 0.400). CONCLUSION: Spirito-Maron score presents a highly
      positive correlation with CMR LV mass and with diastolic dysfunction severity in
      HCM patients. SMS is a reliable quantitative LVH measurement method and seems to
      provide more comprehensive morphological and physiological information than 2D
      echocardiographic conventional parameters used to estimate LVH.

PMID- 24460547
TI  - Recognition rules for binding of Zn-Cys2His2 transcription factors to operator
      DNA.
AB  - The molecules of Zn-finger transcription factors consist of several similar small
      protein units. We analyzed the crystal structures 46 basic units of 22 complexes
      of Zn-Cys2His2 family with the fragments of operator DNA. We showed that the
      recognition of DNA occurs via five protein contacts. The canonical binding
      positions of the recognizing alpha-helix were -1, 3, 6, and 7, which make
      contacts with the tetra-nucleotide sequence ZXYZ of the coding DNA strand; here
      the canonical binding triplet is underlined. The non-coding DNA strand forms only
      one contact at alpha-helix position 2. We have discovered that there is a single
      highly conservative contact His7alpha with the phosphate group of nucleotide Z,
      which precedes each triplet XYZ of the coding DNA chain. This particular contact
      is invariant for the all Zn-Cys2His2 family with high frequency of occurrence
      83%, which we considered as an invariant recognition rule. We have also selected
      a previously unreported Zn-Cys2His2-Arg subfamily of 21 Zn-finger units bound
      with DNA triplets, which make two invariant contacts with residues Arg6alpha and
      His7alpha with the coding DNA chain. These contacts show frequency of occurrence
      100 and 90%, and are invariant recognition rule. Three other variable protein-DNA
      contacts are formed mainly with the bases and specify the recognition patterns of
      individual factor units. The revealed recognition rules are inherent for the Zn
      Cys2His2 family and Zn-Cys2His2-Arg subfamily of different taxonomic groups and
      can distinguish members of these families from any other family of transcription
      factors. 

PMID- 24460548
TI  - Histidinylated poly-L-lysine-based vectors for cancer-specific gene expression
      via enhancing the endosomal escape.
AB  - In this work, we synthesized a series of poly-L-lysine (PLL)-based polymers for
      gene delivery, by modifying the PLL with both cationic peptide and histidine. The
      peptide moieties serve as cationic centers for polyplex formation, and also as
      substrates for protein kinase Calpha (PKCalpha), which is specifically activated
      in many types of cancer cells, to achieve cancer-specific gene expression. The
      histidine groups serve as buffering moieties to increase the ability of the
      plasmid DNA (pDNA)-polymer complex (polyplex) to escape the endosome and thus to
      promote expression of the pDNA in the transfected cells. The facile synthesis of
      the polymers proceeded by modifying the PLL with side-group-protected peptide and
      protected histidine, followed by deprotection of the functional groups. The
      synthesized polymers showed significant buffering capacity over the neutral to
      acidic pH range and showed less cytotoxicity in vitro compared with histidine
      unmodified polymers. The polyplexes successfully showed PKCalpha-responsive gene
      expression immediately after their introduction into cancer cells and the gene
      expression continued for at least 24 h. These PLL-based carriers thus show
      promise for cancer-targeted gene therapy. 

PMID- 24460549
TI  - Functional and phylogenetic diversity of woody plants drive herbivory in a highly
      diverse forest.
AB  - Biodiversity loss may alter ecosystem processes, such as herbivory, a key driver
      of ecological functions in species-rich (sub)tropical forests. However, the
      mechanisms underlying such biodiversity effects remain poorly explored, as mostly
      effects of species richness - a very basic biodiversity measure - have been
      studied. Here, we analyze to what extent the functional and phylogenetic
      diversity of woody plant communities affect herbivory along a diversity gradient
      in a subtropical forest. We assessed the relative effects of morphological and
      chemical leaf traits and of plant phylogenetic diversity on individual-level
      variation in herbivory of dominant woody plant species across 27 forest stands in
      south-east China. Individual-level variation in herbivory was best explained by
      multivariate, community-level diversity of leaf chemical traits, in combination
      with community-weighted means of single traits and species-specific
      phylodiversity measures. These findings deviate from those based solely on trait
      variation within individual species. Our results indicate a strong impact of
      generalist herbivores and highlight the need to assess food-web specialization to
      determine the direction of biodiversity effects. With increasing plant species
      loss, but particularly with the concomitant loss of functional and phylogenetic
      diversity in these forests, the impact of herbivores will probably decrease -
      with consequences for the herbivore-mediated regulation of ecosystem functions. 

PMID- 24460551
TI  - Auxin biosynthetic gene TAR2 is involved in low nitrogen-mediated reprogramming
      of root architecture in Arabidopsis.
AB  - In plants, the plasticity of root architecture in response to nitrogen
      availability largely determines nitrogen acquisition efficiency. One poorly
      understood root growth response to low nitrogen availability is an observed
      increase in the number and length of lateral roots (LRs). Here, we show that low
      nitrogen-induced Arabidopsis LR growth depends on the function of the auxin
      biosynthesis gene TAR2 (tryptophan aminotransferase related 2). TAR2 was
      expressed in the pericycle and the vasculature of the mature root zone near the
      root tip, and was induced under low nitrogen conditions. In wild type plants, low
      nitrogen stimulated auxin accumulation in the non-emerged LR primordia with more
      than three cell layers and LR emergence. Conversely, these low nitrogen-mediated
      auxin accumulation and root growth responses were impaired in the tar2-c null
      mutant. Overexpression of TAR2 increased LR numbers under both high and low
      nitrogen conditions. Our results suggested that TAR2 is required for
      reprogramming root architecture in response to low nitrogen conditions. This
      finding suggests a new strategy for improving nitrogen use efficiency through the
      engineering of TAR2 expression in roots. 

PMID- 24460550
TI  - Cardamine hirsuta: a versatile genetic system for comparative studies.
AB  - A major goal in biology is to identify the genetic basis for phenotypic
      diversity. This goal underpins research in areas as diverse as evolutionary
      biology, plant breeding and human genetics. A limitation for this research is no
      longer the availability of sequence information but the development of functional
      genetic tools to understand the link between changes in sequence and phenotype.
      Here we describe Cardamine hirsuta, a close relative of the reference plant
      Arabidopsis thaliana, as an experimental system in which genetic and transgenic
      approaches can be deployed effectively for comparative studies. We present high
      resolution genetic and cytogenetic maps for C. hirsuta and show that the genome
      structure of C. hirsuta closely resembles the eight chromosomes of the ancestral
      crucifer karyotype and provides a good reference point for comparative genome
      studies across the Brassicaceae. We compared morphological and physiological
      traits between C. hirsuta and A. thaliana and analysed natural variation in
      stamen number in which lateral stamen loss is a species characteristic of C.
      hirsuta. We constructed a set of recombinant inbred lines and detected eight
      quantitative trait loci that can explain stamen number variation in this
      population. We found clear phylogeographic structure to the genetic variation in
      C. hirsuta, thus providing a context within which to address questions about
      evolutionary changes that link genotype with phenotype and the environment. 

PMID- 24460553
TI  - The air gap sign.

PMID- 24460552
TI  - Evaluation of an intensive treatment program for disrupted patient-staff
      relationships in psychiatry.
AB  - PURPOSE: Some patients in psychiatric treatment are considered extremely
      difficult to treat because of the disruptive nature of their relationships with
      treatment staff. In this paper, we describe and evaluate a specialist inpatient
      treatment program for these patients. DESIGN AND METHODS: Data were collected
      from medical records and daily reports of patients (n = 108). Pretest-posttest
      measurements were used to evaluate the treatment. FINDINGS: The main treatment
      method consists of the provision of safety, structure, and cooperation. Treatment
      results show statistically significant changes from admittance to discharge.
      PRACTICE IMPLICATIONS: The collaborative and consistent manner in which nurses
      approach the patients is crucial for quality of care.

PMID- 24460556
TI  - Preparation and characterization of uniform near IR polystyrene nanoparticles.
AB  - Biomaterials for in vivo fluorescence imaging are required to be biocompatible,
      nontoxic, photostable and highly fluorescent. Fluorescence must be in the near
      infrared (NIR) region of the electromagnetic spectrum to avoid absorption and
      autofluorescence of endogenous tissues. NIR fluorescent polystyrene nanoparticles
      may be considered ideal biomaterials for in vivo imaging applications. These NIR
      nanoparticles were prepared by a swelling process of polystyrene template
      nanoparticles with a hydrophobic NIR dye dissolved in a water-miscible swelling
      solvent, a method developed for preparation of nonbiodegradable nanoparticles,
      for NIR fluorescent bioimaging applications. This method overcomes common
      problems that occur with dye entrapment during nanoparticle formation such as
      loss of fluorescence and size polydispersity. Fluorescence intensity of the
      nanoparticles was found to be size dependent, and was optimized for differently
      sized nanoparticles. The resulting NIR nanoparticles were also found to be more
      fluorescent and highly photostable compared to the free dye in solution, showing
      their potential as biomaterials for in vivo fluorescence imaging. 

PMID- 24460557
TI  - The place for sharing.

PMID- 24460558
TI  - Men's health: a commentary.

PMID- 24460559
TI  - Specific design features of an interpretative phenomenological analysis study.
AB  - AIM: Report of an innovative use of interpretative phenomenological analysis
      (IPA) to enable an in-depth study of the experiences of disengagement from mental
      health services of black men with diagnoses of severe and enduring mental
      illness. BACKGROUND: The aim of IPA is to explore the sense that participants
      make of their personal and social worlds, while recognising the contribution of
      the researcher in interpreting the participants' interpretations of their
      experiences. REVIEW METHODS: Seven black male research participants were
      recruited to the study. The components of the study that contribute to the body
      of literature on IPA research design include: an engagement stage in the
      research; a second clarifying interview; discussion of clarifying questions and
      emergent themes with two academic service-users; and a post-interview meeting to
      discuss the themes emerging from the research study. DISCUSSION: The paper
      focuses on the contribution of the four specific design features of the study and
      how these enabled the researcher to engage with a population that is often deemed
      'hard to reach'. CONCLUSION: The four distinctive methodological developments in
      the study emphasise the flexibility of IPA. These innovations assisted the
      researcher in developing a broader double hermeneutic that enabled reporting of
      the experiences of disengagement from mental health services of black men with
      diagnoses of severe and enduring mental illness. IMPLICATIONS FOR
      RESEARCH/PRACTICE: The distinctive design of this study further emphasises the
      flexibility of IPA, while simultaneously showing fidelity to the core principles
      underlying the research methodology.

PMID- 24460560
TI  - Engaging men with penile cancer in qualitative research: reflections from an
      interview-based study.
AB  - AIM: To explore the challenges of engaging men with penile cancer in qualitative
      interview research. BACKGROUND: Qualitative interviewing offers an ideal tool for
      exploring men's experiences of illness, complementing and providing context to
      gendered health inequalities identified in epidemiological research on men. But
      conducting interviews with men can be challenging and embarking on a qualitative
      interview study with males can feel like a daunting task, given the limited
      amount of practical, gender-sensitive guidance for researchers. Reflecting on a
      researcher's experience of conducting qualitative research on men with penile
      cancer, this paper explores the potential challenges of interviewing this group,
      but also documents how engagement and data collection were achieved. REVIEW
      METHODS: This is a reflective paper, informed by the experiences of a male
      researcher (KW) with no nurse training, who conducted 28 interviews with men who
      had been treated for penile cancer. The researcher's experiences are reported in
      chronological order, from the methodological challenges of recruitment to those
      of conducting the interview. IMPLICATIONS FOR PRACTICE/RESEARCH: The paper offers
      a resource for the novice researcher, highlighting some advantages and
      disadvantages of conducting qualitative interview research as a nurse researcher,
      as well as recommendations on how to overcome challenges. CONCLUSION: Engaging
      men with penile cancer in qualitative interview raises practical, methodological,
      ethical and emotional challenges for the researcher. However, when these
      challenges are met, men will talk about their health. Methodological procedures
      must enable an open and ongoing dialogue with clinical gatekeepers and potential
      participants to promote engagement. Support from colleagues is essential for any
      interviewer, no matter how experienced the researcher is.

PMID- 24460561
TI  - Barriers to questionnaire completion: understanding the AIDS/HIV patient's
      perspective.
AB  - AIM: To determine what encourages or discourages AIDS/HIV patients from
      completing questionnaires. BACKGROUND: Data from surveys can provide important
      information but response rates can be poor. Factors that affect this in an HIV
      clinic population have not been assessed previously. REVIEW METHODS: The
      researchers used a qualitative approach and a structured interview schedule. Ten
      patients were recruited and participated in one-to-one interviews. DISCUSSION:
      Most patients saw the potential value of completing a questionnaire in the
      clinic. Lack of privacy during completion was raised as a concern, particularly
      if there were sensitive questions to respond to. Lack of technical competence was
      identified by some as a barrier to participation in electronic surveys. Tickboxes
      were preferred over rating scales or open answers. Participants did not expect a
      cash incentive or entry in a prize draw when asked to complete a questionnaire in
      clinic. CONCLUSION: Generally, AIDS/HIV patients were willing to participate in
      surveys. Availability of a private area to complete the questionnaire, avoiding
      complex electronic systems, completion in the clinic, tickbox answers and a
      length of under two sides of A4 were the most important features that improved
      acceptability of the questionnaire to patients. Implications for research Surveys
      that evaluate care need to be short, easy to complete and have clear relevance to
      the patients' experience.

PMID- 24460562
TI  - Electronic surveys: how to maximise success.
AB  - AIM: To draw on the researchers' experience of developing and distributing a UK
      wide electronic survey. The evolution of electronic surveys in healthcare
      research will be discussed, as well as simple techniques that can be used to
      improve response rates for this type of data collection. BACKGROUND: There is an
      increasing use of electronic survey methods in healthcare research. However, in
      recent published research, electronic surveys have had lower response rates than
      traditional survey methods, such as postal and telephone surveys. REVIEW METHODS:
      This is a methodology paper. DISCUSSION: Electronic surveys have many advantages
      over traditional surveys, including a reduction in cost and ease of analysis.
      Drawbacks to this type of data collection include the potential for selection
      bias and poorer response rates. However, research teams can use a range of simple
      strategies to boost response rates. These approaches target the different stages
      of achieving a complete response: initial attraction through personalisation,
      engagement by having an easily accessible link to the survey, and transparency of
      survey length and completion though targeting the correct, and thereby
      interested, population. CONCLUSION: The fast, efficient and often 'free'
      electronic survey has many advantages over the traditional postal data collection
      method, including ease of analysis for what can be vast amounts of data. However,
      to capitalise on these benefits, researchers must carefully consider techniques
      to maximise response rates and minimise selection bias for their target
      population. IMPLICATIONS FOR RESEARCH/PRACTICE: Researchers can use a range of
      strategies to improve responses from electronic surveys, including sending up to
      three reminders, personalising each email, adding the updated response rate to
      reminder emails, and stating the average time it would take to complete the
      survey in the title of the email.

PMID- 24460563
TI  - Qualitative interviewing: methodological challenges in Arab settings.
AB  - AIM: To explore some of the main methodological challenges faced by interviewers
      in Arab settings, particularly during interviews with psychiatric nurses.
      BACKGROUND: Interviews are a tool used commonly in qualitative research. However,
      the cultural norms and practices of interviewees must be considered to ensure
      that an appropriate interviewing style is used, a good interviewee-interviewer
      relationship formed and consent for participation obtained sensitively. DATA
      SOURCES: A study to explore the nature of psychiatric nurses' practices that used
      unstructured interviews. REVIEW METHODS: This is a methodology paper that
      discusses a personal experience of addressing many challenges that are specific
      to qualitative interviewing in Arab settings, supported by literature on the
      topic. DISCUSSION: Suggestions for improving the interview process to make it
      more culturally sensitive are provided and recommendations for future research
      are made. CONCLUSION: Openness, flexibility and a reflexive approach by the
      researcher can help manage challenges in Arab settings. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Researchers should allow themselves to understand the cultural
      elements of a population to adapt interviewing methods with the aim of generating
      high quality qualitative research.

PMID- 24460564
TI  - Insights into the use and complexities of the Policy Delphi technique.
AB  - AIM: To describe the Policy Delphi technique and show how it was used in a
      research study in the Republic of Ireland. BACKGROUND: Policy Delphi is a variant
      of the Delphi technique, but differs in that its purpose is to explore consensus
      rather than aid it. It is an appropriate methodological tool for researching
      complex issues that benefit from the insights and consensus of a group of
      experts. It is useful in examining options and implications of policy and
      assessing their acceptability. Data sources A three-round policy Delphi study was
      the second phase of a sequential mixed-method design. The study was intended to
      examine stakeholders' perceptions of the clinical role of lecturers in nursing to
      identify supportive and limiting factors that affect the clinical role, with the
      purpose of determining a model for best practice. REVIEW METHODS: A review of
      literature about Policy Delphi from its development to current use (1970-2013)
      was undertaken to explore the technique. DISCUSSION: The complexities of using
      the Policy Delphi methodology to explore policy options are discussed.
      CONCLUSION: Policy Delphi is an underused tool that would benefit nursing
      research. The output from a Policy Delphi study produces a substantial number of
      new ideas and an evaluation of those ideas for use in decision making.
      IMPLICATIONS FOR RESEARCH/PRACTICE: Policy Delphi can offer researchers a means
      to explore levels of consensus on policy issues that have major effects on
      nursing developments. Practitioners may also benefit because it provides a useful
      way to assess and validate expert knowledge that could be contestable in a range
      of practice situations.

PMID- 24460568
TI  - Ex vivo allograft mitral valve leaflet repair prior to orthotopic heart
      transplantation.
AB  - The shortage of donors has limited the number of heart transplantations. We
      report a successful ex vivo mitral valve repair of the allograft prior to heart
      transplantation.

PMID- 24460570
TI  - Persistent left superior vena cava with absent right superior vena cava: review
      of the literature and clinical implications.
AB  - Persistent left superior vena cava (PLSVC) is the most common venous anomaly of
      the thorax affecting 0.5-2% of the general population. PLSVC with absent right
      SVC, which is also referred to as isolated PLSVC, occurs in 0.09-0.13% of
      patients. PLSVC should be suspected whenever a dilated coronary sinus is
      discovered on transthoracic echocardiography. Transthoracic echocardiography
      serves as an excellent modality to diagnose PLSVC. The presence of PLSVC can be
      confirmed by performing a bilateral "bubble study" with injection of agitated
      saline from both the left and the right peripheral arm veins. Although PLSVC is a
      benign condition, it may have important clinical implications in certain
      situations. We describe a case of PLSVC with an absent right SVC followed by a
      review of the literature and the clinical implications associated with this
      condition. 

PMID- 24460571
TI  - Photodecomposition of chloroform catalyzed by unmodified MCM-41 mesoporous
      silica.
AB  - Unactivated MCM-41 mesoporous silica catalyzes the photodecomposition of
      chloroform to phosgene and hydrogen chloride under near-UV (lambda > 360 nm)
      irradiation. The rate of photodecomposition increases toward an asymptotic limit
      as the O(2) partial pressure is increased. Deuterochloroform does not decompose
      under the same experimental conditions. Low concentrations of both cyclohexane
      and ethanol quench the photodecomposition, whereas water, up to its solubility
      limit, does not. Dissolved tetraalkylammonium salts suppress photodecomposition.
      The data are consistent with a mechanism in which light absorption by an SiO(2)
      defect yields an electron-deficient oxygen atom, which then abstracts hydrogen
      from chloroform. The resulting CCl(3) radicals react with oxygen to form a peroxy
      radical that decomposes, eventually yielding phosgene and hydrogen chloride.

PMID- 24460572
TI  - The regulated synthesis of a Bacillus anthracis spore coat protein that affects
      spore surface properties.
AB  - AIMS: Examine the regulation of a spore coat protein and the effects on spore
      properties. METHODS AND RESULTS: A c. 23 kDa band in coat/exosporial extracts of
      Bacillus anthracis Sterne spores varied in amount depending upon the conditions
      of sporulation. It was identified by MALDI as a likely orthologue of ExsB of
      Bacillus cereus. Little if any was present in an exosporial preparation with a
      location to the inner coat/cortex region established by spore fractionation and
      immunogold labelling of electron micrograph sections. Because of its predominant
      location in the inner coat, it has been renamed Cotgamma. It was relatively
      deficient in spores produced at 37 degrees C and when acidic fermentation
      products were produced a difference attributable to transcriptional regulation.
      The deficiency or absence of Cotgamma resulted in a less robust exosporium
      positioned more closely to the coat. These spores were less hydrophobic and
      germinated somewhat more rapidly. Hydrophobicity and appearance were rescued in
      the deletion strain by introduction of the cotgamma gene. CONCLUSIONS: The
      deficiency or lack of a protein largely found in the inner coat altered spore
      hydrophobicity and surface appearance. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      regulated synthesis of Cotgamma may be a paradigm for other spore coat proteins
      with unknown functions that modulate spore properties in response to
      environmental conditions.

PMID- 24460574
TI  - Early postoperative mortality after surgery for rectal cancer in Sweden, 2000
      2011.
AB  - AIM: Postoperative mortality has traditionally been defined as death within 30
      days of surgery. Such mortality after rectal cancer resection has declined
      significantly during the last decades. However, it is possible that this decline
      can be explained merely by a shift towards an increase in 90-day mortality.
      METHOD: A nationwide cohort study was based on data from the Swedish Colorectal
      Cancer Registry and the Swedish Patient Registry concerning patients who had
      undergone surgical resection for rectal cancer in 2000-2011. Unconditional
      logistic regression was used to calculate ORs with 95% CIs regarding mortality in
      different calendar periods (2000-2003, 2004-2007 and 2008-2011) in two different
      postoperative time periods (0-30 days and 31-90 days). RESULTS: Some 15,437
      patients were included in this surgical cohort. Mortality within 30 days of
      surgery decreased from 2.1% in 2000-2003 to 1.6% in 2008-2011, whilst the
      corresponding mortality within the 31- to 90-day time window decreased from 2.1%
      to 1.4%. The adjusted risk of 30-day mortality in 2008-2011 was statistically
      significantly decreased compared with that in 2000-2003 (OR = 0.67; 95% CI: 0.48
      0.93) and mortality in the 31- to 90-day time window was also reduced for 2008
      2011 compared with 2000-2003 (OR = 0.71; 95% CI: 0.51-0.99). CONCLUSION: This
      population-based, nationwide Swedish study indicates that postoperative
      mortality, as measured within 30 days and 31-90 days after surgery, has decreased
      with time. However, no relevant shift from earlier to later postoperative
      mortality was discerned.

PMID- 24460576
TI  - Opioids and driving ability: current data do not support one opioid being more
      favorable than another.

PMID- 24460577
TI  - Antidepressants in the treatment for chronic low back pain: questioning the
      validity of meta-analyses.
AB  - OBJECTIVES: To contrast the analgesic effect of duloxetine with antidepressants
      reported in other published randomized clinical trials (RCTs) and review articles
      in patients with chronic low back pain (CLBP). METHODS: In this narrative review,
      the results of 13 RCTs and 5 systematic reviews examining the analgesic effect of
      various antidepressants in CLBP were contrasted with those of 3 placebo
      controlled duloxetine RCTs. Treatment effects based on the Brief Pain Inventory
      (BPI) average score in the duloxetine RCTs were assessed in all completers (by
      study and overall) and in last-observation-carried-forward (LOCF) analyses
      (extracted from study reports). 30%- and 50%-reduction response rates were
      compared between duloxetine and placebo. RESULTS: Eleven different
      antidepressants were examined in 13 individual RCTs. Sample sizes, treatment
      durations, and analysis methods varied across studies. Reviews each included 5 to
      9 of the RCTs and came to different conclusions regarding the analgesic effect of
      antidepressants: 2 found no evidence while 3 reported some evidence. The
      completer analysis showed greater improvements in BPI average scores with
      duloxetine vs. placebo (significant in 2 studies). Overall, the least square mean
      (standard error) difference between treatments was - 0.7 (0.15) (P < 0.0001).
      Overall response rates were significantly larger with duloxetine than with
      placebo. CONCLUSIONS: Due to the diversity of previous studies and the pooling
      methods used, the conclusions regarding the analgesic effect of antidepressants
      in CLBP drawn from systematic reviews must be interpreted with caution.
      Appropriately designed and powered studies similar to recently published
      duloxetine studies are recommended to demonstrate the analgesic effect of
      antidepressants.

PMID- 24460575
TI  - Role of a histamine 4 receptor as an anti-inflammatory target in carrageenan
      induced pleurisy in mice.
AB  - The histamine 4 receptor (H4R) is expressed primarily on cells involved in
      inflammation and immune responses. Despite much research into inflammatory
      diseases, no drugs with favourable safety profiles are yet available for their
      treatment. The aim of the present study was to determine the potential anti
      inflammatory effect of 4-methylhistamine (4-MeH) or JNJ77777120 (JNJ) and to
      explore the role of H4R in a mouse model of carrageenan (Cg) -induced pleurisy. A
      single dose of 4-MeH or JNJ (30 mg/kg) was administered intraperitoneally 1 hr
      before Cg administration. The results illustrate that both the numbers of CD4(+)
      , CD25(+) , CD4(+)  CD25(+) , GITR(+) , GITR(+)  IL-17A(+) -expressing T cells
      and the levels of T helper type 1 (Th1)/Th17 cytokines were markedly increased in
      both the Cg-treated and 4-MeH-treated groups, whereas the cytokines produced by
      Th2 cells were significantly decreased in the same groups. However, JNJ treatment
      significantly decreased both the number of T-cell subsets and GITR(+) , GITR(+) 
      IL-17A(+) -expressing T cells, and the production of Th1/Th17 cytokines. Further,
      JNJ up-regulated the expression of the Th2 cytokines. RT-PCR analysis revealed an
      increased expression of interleukin-1beta, tumour necrosis factor-alpha, monocyte
      chemoattractant protein-1 and intercellular adhesion molecule-1 in the Cg-treated
      and 4-MeH-treated groups, which was reduced by treatment with JNJ in lung
      tissues. Moreover, histological examinations revealed anti-inflammatory effects
      of JNJ, whereas 4-MeH worsened Cg-induced inflammation. In conclusion, the
      results of the present work clearly indicate that JNJ possesses important anti
      inflammatory properties that are increased in 4-MeH-treated mice, suggesting that
      H4R are involved in pleurisy and that JNJ has an anti-inflammatory effect in
      associated disease conditions. 

PMID- 24460578
TI  - Extraforaminal compression of the L-5 nerve root at the lumbosacral junction:
      clinical analysis, decompression technique, and outcome.
AB  - OBJECT: Extraforaminal compression of the L-5 nerve encompasses multiple
      pathological entities and may result from disc herniations as well as bony
      (osteophytes or sacral ala) or ligamentous (sacroiliac ligament and lumbosacral
      band) compression. Several other factors, such as disc space collapse or coronal
      wedging, can also contribute to narrowing of the extraforaminal space. The
      extraforaminal space at L5-S1 has unique anatomical features compared with the
      upper lumbar levels, which makes surgical access to this region difficult.
      Minimally invasive techniques offer easier access to the region. The purpose of
      this study was to analyze the contributing factors for extraforaminal compression
      of the L-5 nerve and assess clinical outcome following surgical decompression.
      METHODS: Fifty-two consecutive patients who underwent a minimally invasive far
      lateral approach for extraforaminal compression of the L-5 nerve were
      retrospectively analyzed for clinical data, outcomes, and imaging features (type
      of disc prolapse, coronal wedging, degree of disc and facet degeneration, facet
      tropism, foraminal stenosis, osteophytes, and adjacent-level disease). The
      authors describe the surgical technique used in this study. RESULTS: The mean age
      of the patient sample was 57 years. Sixteen patients each had an extraforaminal
      ruptured disc or contained protrusion, and the remaining 20 patients had disc
      protrusions extending into the foraminal region or the lateral recess. Associated
      foraminal stenosis was found in 38.5%, and adjacent-level stenosis was noted in
      22 cases (42.3%) and spondylolisthesis in 4 (7.7%). Osteophytes were noted in 18
      cases. A coronal wedging angle >= 3 degrees  was found in 46.2%, and the
      laterality of wedging corresponded to the symptomatic side in 91% of cases.
      Fifteen patients (28.8%) complained of postoperative dysesthesias, which
      completely resolved in all cases within 6 months. The incidence of dysesthesias
      was more common in the ruptured disc group. There were no differences in clinical
      outcome among the different types of disc prolapses. The mean preoperative and
      postoperative visual analog scale scores were 7.6 and 3.6, respectively. The mean
      preoperative and postoperative Japanese Orthopaedic Association (JOA) scores were
      6.4 and 13.8, respectively. The mean JOA recovery rate was 86.1%. According to
      the Macnab functional grading system, 96% of the patients had excellent or good
      grades at follow-up. CONCLUSIONS: A minimally invasive far-lateral approach to L5
      S1 requires a good understanding of the regional anatomy and can provide good to
      excellent clinical results in properly selected cases. This approach is effective
      in decompressing the far-lateral and foraminal zones. Adequate preoperative
      diagnosis and tailoring the surgical procedure to address the relevant
      compressive element in each case is essential to achieving good clinical results.

PMID- 24460579
TI  - Degenerative disc disease and osteoporosis.

PMID- 24460580
TI  - Gait-simulating fatigue loading analysis and sagittal alignment failure of spinal
      pelvic reconstruction after total sacrectomy: comparison of 3 techniques.
AB  - OBJECT: Reconstruction after total sacrectomy is a critical component of
      malignant sacral tumor resection, permitting early mobilization and maintenance
      of spinal pelvic alignment. However, implant loosening, graft migration, and
      instrumentation breakage remain major problems. Traditional techniques have used
      interiliac femoral allograft, but more modern methods have used fibular or cage
      struts from the ilium to the L-5 endplate or sacral body replacement with
      transiliac bars anchored to cages to the L-5 endplate. This study compares the
      biomechanical stability under gait-simulating fatigue loading of the 3 current
      methods. METHODS: Total sacrectomy was performed and reconstruction was completed
      using 3 different constructs in conjunction with posterior spinal screw rod
      instrumentation from L-3 to pelvis: interiliac femur strut allograft (FSA); L5
      iliac cage struts (CSs); and S-1 body replacement expandable cage (EC). Intact
      lumbar specimens (L3-sacrum) were tested for flexion-extension range of motion
      (FE-ROM), axial rotation ROM (AX-ROM), and lateral bending ROM (LB-ROM). Each
      instrumented specimen was compared with its matched intact specimen to generate
      an ROM ratio. Fatigue testing in compression and flexion was performed using a
      custom-designed long fusion gait model. RESULTS: Compared with intact specimen,
      the FSA FE-ROM ratio was 1.22 +/- 0.60, the CS FE-ROM ratio was significantly
      lower (0.37 +/- 0.12, p < 0.001), and EC was lower still (0.29 +/- 0.14, p <
      0.001; values are expressed as the mean +/- SD). The difference between CS and EC
      in FE-ROM ratio was not significant (p = 0.83). There were no differences in AX
      ROM or LB-ROM ratios (p = 0.77 and 0.44, respectively). No failures were noted on
      fatigue testing of any EC construct (250,000 cycles). This was significantly
      improved compared with FSA (856 cycles, p < 0.001) and CS (794 cycles, p <
      0.001). CONCLUSIONS: The CS and EC appear to be significantly more stable
      constructs compared with FSA with FE-ROM. The 3 constructs appear to be equal
      with AX-ROM and LB-ROM. Most importantly, EC appears to be significantly more
      resistant to fatigue compared with FSA and CS. Reconstruction of the load
      transfer mechanism to the pelvis via the L-5 endplate appears to be important in
      maintenance of alignment after total sacrectomy reconstruction.

PMID- 24460581
TI  - Effects of curcumin on acute spinal cord ischemia-reperfusion injury in rabbits.
      Laboratory investigation.
AB  - OBJECT: The object of this study was to conduct a prospective, randomized,
      laboratory investigation of the neuroprotective effects of curcumin functionally,
      biochemically, and histologically in an experimental acute spinal cord ischemia
      reperfusion injury on rabbits. METHODS: Eighteen rabbits were randomly assigned
      to 1 of 3 groups: the sham group, the ischemia-reperfusion group, or the curcumin
      group. Spinal cord ischemia was induced by applying an infrarenal aortic cross
      clamp for 30 minutes. At 48 hours after ischemia, neurological function was
      evaluated with modified Tarlov criteria. Biochemical changes in the spinal cord
      and plasma were observed by measuring levels of malondialdehyde (MDA), advanced
      oxidation protein products (AOPP), glutathione (GSH), superoxide dismutase (SOD),
      catalase (CAT), nitrite/nitrate, and tumor necrosis factor-alpha (TNF-alpha).
      Histological changes were examined with H & E staining. Immunohistochemical
      staining with antibodies against caspase-3 was performed to evaluate cell
      apoptosis after ischemia. RESULTS: In the curcumin group, neurological outcome
      scores were statistically significantly better compared with the ischemia
      reperfusion group. In the ischemia-reperfusion group, MDA, AOPP, and
      nitrite/nitrate levels were significantly elevated in the spinal cord tissue and
      the plasma by the induction of ischemia-reperfusion. The curcumin treatment
      significantly prevented the ischemia-reperfusion-induced elevation of
      nitrite/nitrate and TNF-alpha. In addition, the spinal cord tissue and the plasma
      SOD, GSH, and CAT levels were found to be preserved in the curcumin group and not
      statistically different from those of the sham group. Histological evaluation of
      the tissues also demonstrated a decrease in axonal damage, neuronal degeneration,
      and glial cell infiltration after curcumin administration. CONCLUSIONS: Although
      further studies including different dose regimens and time intervals are
      required, curcumin could attenuate a spinal cord ischemia-reperfusion injury in
      rabbits via reducing oxidative products and proinflammatory cytokines, as well as
      increasing activities of antioxidant enzymes and preventing apoptotic cell death.

PMID- 24460582
TI  - Induction of neurotrophic and differentiation factors in neural stem cells by
      valproic acid.
AB  - Valproic acid (VPA), a short-chain fatty acid, is used clinically as an
      anticonvulsant and mood stabilizer. Valproic acid also inhibits histone
      deacetylase activity, which is associated with histone hyperacetylation and
      changes in gene expression. In this study, we examined the effects of VPA on the
      expression of selected neurotrophic and differentiation factors in C17.2 neural
      stem cells. Reverse transcription-polymerase chain reaction analysis revealed a
      significant increase in conserved dopamine neurotrophic factor (CDNF) and glial
      cell line-derived neurotrophic factor mRNA expression, after treatment with
      clinically relevant concentrations of VPA (0.5 or 1.0 mM) for 24 hr. Increases in
      the protein expression of CDNF and mesencephalic astrocyte-derived neurotrophic
      factor were also observed, after similar treatment with VPA. In addition,
      significant increases in the mRNA levels of the early dopaminergic neuron marker,
      nuclear receptor-related protein 1(Nurr1), and the transcriptional regulator,
      early growth response protein 1 (Egr1), were observed after treatment with VPA
      for 24 hr. C17.2 neural stem cells exhibited high basal mRNA expression of brain
      derived neurotrophic factor and SRY (sex determining region Y)-box 2 (Sox2),
      which was not altered by VPA treatment. Western analysis revealed
      hyperacetylation of histone H3 proteins in C17.2 cells after VPA treatment for 24
      hr or 48 hr, suggesting involvement of an epigenetic mechanism in the observed
      gene induction by this drug. These findings support a role for VPA in modulating
      neurotrophic and differentiation factor expression, in keeping with its reported
      neuroprotective and neurodevelopmental effects.

PMID- 24460583
TI  - Synchronized parallel deployment of vascular plugs for treating large aneurysms
      of pulmonary arteries.
AB  - We report an endovascular technique for the treatment of large neck pulmonary
      artery aneurysms. This technique consists of the synchronized parallel deployment
      of two vascular plugs.

PMID- 24460584
TI  - Disseminated adenovirus infection in kidney transplant recipient.
AB  - Adenoviruses are common pathogens that have the potential to cause opportunistic
      infections with significant morbidity and mortality in immunocompromised hosts.
      The significance of adenoviral infection and disease is incompletely known in the
      setting of kidney transplantation. Reported adenovirus infections in renal
      transplant recipients have typically manifested as haemorrhagic cystitis and
      tubulointerstitial nephritis. Pneumonia, hepatitis and enteritis are often seen
      in other solid organ recipients. However, disseminated or severe adenovirus
      infections, including fatal cases, have been described in renal transplant
      recipients. There is uncertainty regarding monitoring and treatment of this
      virus. Although not supported by randomized clinical trials, cidofovir is used
      for the treatment of adenovirus disease not responding to reduction of
      immunosuppression. We present a case series of 2 patients with disseminated
      adenovirus infection in our centre who presented at different times from the time
      of transplantation. 

PMID- 24460585
TI  - Bistable retinal schiff base photodynamics of histidine kinase rhodopsin HKR1
      from Chlamydomonas reinhardtii.
AB  - The photodynamics of the recombinant rhodopsin fragment of the histidine kinase
      rhodopsin HKR1 from Chlamydomonas reinhardtii was studied by absorption and
      fluorescence spectroscopy. The retinal cofactor of HKR1 exists in two Schiff base
      forms RetA and RetB. RetA is the deprotonated 13-cis-retinal Schiff base (RSB)
      absorbing in the UVA spectral region. RetB is the protonated all-trans RSB
      absorbing in the blue spectral region. Blue light exposure converts RetB fully to
      RetA. UVA light exposure converts RetA to RetB and RetB to RetA giving a mixture
      determined by their absorption cross sections and their conversion efficiencies.
      The quantum efficiencies of conversion of RetA to RetB and RetB to RetA were
      determined to be 0.096 +/- 0.005 and 0.405 +/- 0.01 respectively. In the dark
      thermal equilibration between RetA and RetB with dominant RetA content occurred
      with a time constant of about 3 days at room temperature. The fluorescence
      emission behavior of RetA and RetB was studied, and fluorescence quantum yields
      of phi(F) (RetA) = 0.00117 and phi(F) (RetB) = 9.4 * 10(-5) were determined.
      Reaction coordinate schemes of the photodynamics are developed.

PMID- 24460586
TI  - Evaluation of stroke volume and ventricular mass in a fetal heart model: a novel
      four-dimensional echocardiographic analysis.
AB  - AIMS: This study aimed to assess the feasibility and accuracy of nongated four
      dimensional echocardiography (4DE) for determining left ventricular (LV) stroke
      volume (SV) and mass in a fetal heart-sized LV model. METHODS: A balloon was
      inserted into the LV of 20 fresh rabbit hearts and attached to a calibrated
      pulsatile pump. Ten hearts retaining the right ventricle were imaged in Group A.
      Ten hearts without the right ventricles (RVs) attached were imaged in Group B.
      Nongated 4D volumes were obtained using a Philips iU-22 system with an X6-1
      matrix probe at SVs ranging from 1 to 5 mL at increments of 1 mL. At each SV, the
      volume displacement of the heart was measured at end-systole and end-diastole.
      Mass was determined by displacement at the conclusion of the experiment. RESULTS:
      The images were analyzed offline by manually tracing endocardial and epicardial
      boundaries of stacked contours. An excellent correlation in SV and mass between
      echo-derived values and displacement values was demonstrated and accompanied by
      high coefficients of determination (R2 ) in both groups (SV: Group A: R2 =
      0.9461, Group B: R2 = 0.9811; Mass: Group A: R2 = 0.9223, Group B: R2 = 0.9602;
      all P < 0.001). Bland-Altman analyses showed a slight overestimation in both
      groups for both SV and LV mass. CONCLUSIONS: Nongated 4DE was demonstrated to be
      feasible and that it could accurately define SV and ventricular mass for a fetal
      heart-sized LV model.

PMID- 24460587
TI  - Distribution and abundance of human-specific Bacteroides and relation to
      traditional indicators in an urban tropical catchment.
AB  - AIMS: The study goals were to determine the relationship between faecal indicator
      bacteria (FIB), the HF183 marker and land use, and the phylogenetic diversity of
      HF183 marker sequences in a tropical urban watershed. METHODS AND RESULTS: Total
      coliforms, Escherichia coli, and HF183 were quantified in 81 samples categorized
      as undeveloped, residential and horticultural from the Kranji Reservoir and
      Catchment in Singapore. Quantitative-PCR for HF183 followed by analysis of
      variance indicated that horticultural areas had significantly higher geometric
      means for marker levels (4.3 * 10(4) HF183-GE 100 ml(-1)) than nonhorticultural
      areas (3.07 * 10(3) HF183-GE 100 ml(-1)). E. coli and HF183 were moderately
      correlated in horticultural areas (R = 0.59, P = 0.0077), but not elsewhere in
      the catchment. Initial upstream surveys of candidate sources revealed elevated
      HF183 in a wastewater treatment effluent but not in aquaculture ponds. The HF183
      marker was cloned, sequenced and determined by phylogenetic analysis to match the
      original marker description. CONCLUSION: We show that quantification of the HF183
      marker is a useful tool for mapping the spatial distribution and potential
      sources of human sewage contamination in tropical environments such as Singapore.
      SIGNIFICANCE AND IMPACT: A major challenge for assessment of water quality in
      tropical environments is the natural occurrence and nonconservative behaviour of
      FIB. The HF183 marker has been employed in temperate environments as an
      alternative indicator for human sewage contamination. Our study supports the use
      of the HF183 marker as an indicator for human sewage in Singapore and motivates
      further work to determine HF183 marker levels that correspond to public health
      risk in tropical environments.

PMID- 24460588
TI  - Laparoscopic intersphincteric resection for low rectal cancer: comparison of
      stapled and manual coloanal anastomosis.
AB  - AIM: The study aim was to analyse the safety and feasibility of laparoscopic
      intersphincteric resection with stapled coloanal anastomosis for low rectal
      cancer. METHOD: Between March 2009 and August 2010, 22 patients underwent
      laparoscopic intersphincteric resection with a stapled coloanal anastomosis
      without a diverting ileostomy. The results were compared retrospectively with
      hand-sewn coloanal anastomoses performed between January 2001 and May 2009, which
      included 55 open and 38 laparoscopic intersphincteric resections. The morbidity
      comparison only included data relevant to the anastomosis. Function was compared
      using the Saito function questionnaire and the Wexner score and only involved
      data relevant to the laparoscopy. RESULTS: The anastomotic complication rates
      were similar for fistula, bleeding and neorectal mucosal prolapse (P = 0.526, P =
      0.653 and P = 0.411, respectively). Anastomotic leakage and stricture formation
      of the stapled coloanal anastomosis were significantly lower than those of the
      hand-sewn coloanal anastomosis (P = 0.037 and P = 0.028, respectively). There
      were no significant differences in the Saito function questionnaire and the
      Wexner score between the stapled and hand-sewn coloanal anastomotic groups (all P
      > 0.05). CONCLUSION: Laparoscopic intersphincteric resection with a stapled
      coloanal anastomosis is technically feasible and is less likely to result in
      anastomotic leakage and stricture formation than a hand-sewn anastomosis.

PMID- 24460589
TI  - The investigation of non-invasive techniques for treating early approximal
      carious lesions: an in vivo study.
AB  - OBJECTIVES: The aim of this study was to examine non-cavitated approximal caries
      using non-invasive treatment methods. MATERIALS AND METHODS: Molar and premolar
      teeth with approximal caries were used in this in vivo study. Approximal caries
      lesions were evaluated with visual and radiographic inspection and with the
      DIAGNOdent device. Five groups were formed to study non-invasive treatment, and
      each had at least 25 early approximal carious lesions. Patients in the control
      group were not treated. After the separation, either ozone application,
      acidulated phosphate fluoride gel, CPP-ACP-containing material (Tooth Mousse), or
      an antibacterial bonding agent (Clearfil Protect Bond) was used. For 18 months
      after the non-invasive treatment, radiological controls were used to observe the
      progress of the initial and approximal caries in the 1st, 3rd, 6th and 12th
      months of follow-up. A Mann-Whitney U-test was used to perform the statistical
      analysis; in-group comparisons were made with the Wilcoxon signed-rank test, and
      a quantitative assessment was performed using a chi-squared test. RESULTS: At the
      end of 18 months, the caries lesions in the control group were observed to
      progress (P < 0.01). The lesions that were scored as 1a during a visual
      inspection recovered by using non-invasive treatments. CONCLUSION: Approximal
      caries lesions that were detected at the early stages remained stationary when
      using antibacterial agents and materials that promoted remineralisation. CLINICAL
      RELEVANCE: Antibacterial agents and remineralisation materials can be used in
      treatment of early approximal caries lesions.

PMID- 24460590
TI  - The neuromuscular approach towards interdisciplinary cooperation in medicine.
AB  - BACKGROUND: The contemporary approach of dentistry towards interdisciplinary
      cooperation is based on the neuromuscular concept. In recent years many authors
      have pointed out a correlation between orthopaedic and dental findings.
      Furthermore, there is an intimate biomechanical interrelationship of occlusion
      with cerebral fluid circulation, left and right equilibrium, gaze stabilisation
      and headache. The influence of a dental occlusion and temporomandibular joint
      (TMJ) status on general health has been widely analysed in the current scientific
      literature. AIM: The aim of this analytic study was to display the deep
      relationship between dentistry and other fields of medicine, and to show the
      necessity of wide cooperation between dentists and physicians. CONCLUSIONS: This
      study was based on a review of 41 sources, including specialised articles and
      books. The significance of different anatomical and physiological preconditions
      (occlusion, muscles and TMJ status) was considered and evaluated separately.
      However, as a result of modern concepts of general body health, extending
      cooperation between different fields of medicine is essential. The practical
      application of the principles of neuromuscular dentistry enables one to increase
      greatly the treatment efficiency of aches in muscles, headaches, postural
      dysfunctions as well as of many other diseases. However, the dentist's
      contribution to the development of an interdisciplinary approach is
      underestimated. Many theoretical aspects of the interdisciplinary relationship
      have not been sufficiently examined, hence the practical consequences remain
      unclear. Further research in the field is urgently needed.

PMID- 24460591
TI  - Turning Australia into a 'flat-land': what are the implications for workforce
      supply of addressing the disparity in rural-city dentist distribution?
AB  - Dentistry in Australia has faced, and continues to face, significant workforce
      issues, in particular, a grossly distorted workforce distribution. In this study,
      an analysis of the consequences for the workforce that would occur under a series
      of reduced maldistribution scenarios is examined and reported. Three different
      scenarios were tested based on existing dental practice to population data at a
      national level. This study clearly highlights the very significant
      maldistribution of practices in Australia. However, more importantly, it
      highlights that to address this maldistribution requires something in the order
      of a tenfold increase in dental practice numbers (and the commensurate increase
      in workforce), which is not possible (or reasonable). As a nation, Australia has
      to look to other methods of achieving equity in access to good oral health. The
      application of modes of care delivery including, but not limited to visiting
      services needs to be examined and extended. Clearly, these new methodologies are
      going to rely on non-dental health professionals taking a far more significant
      role in leading oral health-care models as well as the expanded application of
      technology to bring unique skill bases to areas where these skilled individuals
      do not (and will not) reside. 

PMID- 24460594
TI  - Infectious endophthalmitis in Boston keratoprosthesis: incidence and prevention.
AB  - PURPOSE: To determine the cumulative worldwide incidence of infectious
      endophthalmitis and associated vision loss after Boston keratoprosthesis (B-KPro)
      Type I/II implantation and to propose both safe and inexpensive prophylactic
      antibiotic regimens. METHODS: Two retrospective methods were used to determine
      the incidence, visual outcomes and aetiologies of infectious endophthalmitis
      associated with the B-KPro divided per decade: (i) systematic review of the
      literature from 1990 through January 2013 and (ii) a surveillance survey sent to
      all surgeons who implanted B-KPros through 2010 with 1-year minimum follow-up. In
      addition, a single-Boston surgeon 20-year experience was examined. RESULTS: From
      1990 through 2010, there were 4729 B-KPros implanted worldwide by 209 U.S.
      surgeons and 159 international surgeons. The endophthalmitis cumulative mean
      incidence declined from 12% during its first decade of use to about 3% during its
      second decade in the Unites States and about 5% internationally during the second
      decade. There remains a large incidence range both in the United States (1-12.5%)
      and internationally (up to 17%). Poor compliance with daily topical antibiotics
      is an important risk factor. While Gram-positive organisms remained dominant,
      fungal infections emerged during the second decade. CONCLUSIONS: Daily
      prophylactic topical antibiotics have dramatically reduced the endophthalmitis
      incidence. Although Gram-positive organisms are the most common aetiology,
      antimicrobials must be inclusive of Gram-negative organisms. Selection of
      prophylactic regimens should be tailored to local antibiotic susceptibility
      patterns, be cost-effective, and should not promote the emergence of
      antimicrobial resistance. An example of a broad-spectrum, low-cost prophylactic
      option for non-autoimmune patients includes trimethoprim/polymyxinB once daily.

PMID- 24460592
TI  - The NS segment of H5N1 avian influenza viruses (AIV) enhances the virulence of an
      H7N1 AIV in chickens.
AB  - Some outbreaks involving highly pathogenic avian influenza viruses (HPAIV) of
      subtypes H5 and H7 were caused by avian-to-human transmissions. In nature,
      different influenza A viruses can reassort leading to new viruses with new
      characteristics. We decided to investigate the impact that the NS-segment of H5
      HPAIV would have on viral pathogenicity of a classical avian H7 HPAIV in poultry,
      a natural host. We focussed this study based on our previous work that
      demonstrated that single reassortment of the NS-segment from an H5 HPAIV into an
      H7 HPAIV changes the ability of the virus to replicate in mammalian hosts. Our
      present data show that two different H7-viruses containing an NS-segment from H5
      types (FPV NS GD or FPV NS VN) show an overall highly pathogenic phenotype
      compared with the wild type H7-virus (FPV), as characterized by higher viral
      shedding and earlier manifestation of clinical signs. Correlating with the
      latter, higher amounts of IFN-beta mRNA were detected in the blood of NS
      reassortant infected birds, 48 h post-infection (pi). Although lymphopenia was
      detected in chickens from all AIV-infected groups, also 48 h pi those animals
      challenged with NS-reassortant viruses showed an increase of peripheral
      monocyte/macrophage-like cells expressing high levels of IL-1beta, as determined
      by flow cytometry. Taken together, these findings highlight the importance of the
      NS-segment in viral pathogenicity which is directly involved in triggering
      antiviral and pro-inflammatory cytokines found during HPAIV pathogenesis in
      chickens. 

PMID- 24460595
TI  - An overview of the statistical methods reported by studies using the Canadian
      community health survey.
AB  - BACKGROUND: The Canadian Community Health Survey (CCHS) is a cross-sectional
      survey that has collected information on health determinants, health status and
      the utilization of the health system in Canada since 2001. Several hundred
      articles have been written utilizing the CCHS dataset. Previous analyses of
      statistical methods utilized in the literature have focused on a particular
      journal or set of journals to understand the statistical literacy required for
      understanding the published research. In this study, we describe the statistical
      methods referenced in the published literature utilizing the CCHS dataset(s).
      METHODS: A descriptive study was undertaken of references published in Medline,
      Embase, Web of Knowledge and Scopus associated with the CCHS. These references
      were imported into a Java application utilizing the searchable Apache Lucene text
      database and screened based upon pre-defined inclusion and exclusion criteria.
      Full-text PDF articles that met the inclusion criteria were then used for the
      identification of descriptive, elementary and regression statistical methods
      referenced in these articles. The identification of statistical methods occurred
      through an automated search of key words on the full-text articles utilizing the
      Java application. RESULTS: We identified 4811 references from the 4
      bibliographical databases for possible inclusion. After exclusions, 663
      references were used for the analysis. Descriptive statistics such as means or
      proportions were presented in a majority of the articles (97.7%). Elementary
      level statistics such as t-tests were less frequently referenced (29.7%) than
      descriptive statistics. Regression methods were frequently referenced in the
      articles: 79.8% of articles contained reference to regression in general with
      logistic regression appearing most frequently in 67.1% of the articles.
      CONCLUSIONS: Our study shows a diverse set of analysis methods being referenced
      in the CCHS literature, however, the literature heavily relies on only a subset
      of all possible statistical tools. This information can be used in identifying
      gaps in statistical methods that could be applied to future analysis of public
      health surveys, insight into training and educational programs, and also
      identifies the level of statistical literacy needed to understand the published
      literature.

PMID- 24460596
TI  - Effects of daily energy expenditure on academic performance of elementary
      students in Taiwan.
AB  - AIM: The objective of the study was to investigate the potential effects of daily
      energy expenditure on the academic performance (AP) of elementary schoolchildren,
      the results of which will be used as the basis of planning physical activity (PA)
      for children in the future. METHODS: Participants were collected from 4th to 6th
      grade children at an elementary school in southern Taiwan. The effective sample
      data size was 1065 (79.8%; 528 boys and 537 girls). Daily mean energy expenditure
      was obtained using the 3 Day Physical Activity Recall (3-DPAR), and the intensive
      activities degrees of physical activity were categorized into lowest PA, middle
      PA, and highest PA group, and academic performance assessed with weighted
      academic score. RESULTS: The significant effect on the academic performance of
      schoolchildren was only in energy expenditure but not for sexes and tutorials
      attended. All students in the middle PA group performed better academically than
      those in the highest PA group. After controlling sexes, male students in the
      middle PA group performed better than other groups; female students in the lowest
      PA group performed better than other groups. CONCLUSION: These results may be
      consulted by schools, academic faculties, and parents in setting up exercise
      plans for children.

PMID- 24460597
TI  - Effectiveness of orientation tour on children's anxiety before elective
      surgeries.
AB  - AIM: The purpose of this study was to investigate the effectiveness of an
      orientated tour in reduction of children's anxiety before elective surgeries.
      Anxiety is a common emotional reaction following surgical experience among
      children that can result in increasing postoperative pain, increasing analgesic
      use. METHODS: The study was a blinded clinical trial; 70 children were randomized
      into two groups (intervention and control). All children received standard
      preoperative care, while those in the intervention group also received an
      orientated tour with their mother of the operation room the night before the
      surgery was carried out. The children's anxiety was assessed by the "Child
      Drawing: Hospital" instrument and vital signs measured before and after
      intervention in both groups. Data were analyzed with SPSS ver. 11.5 software.
      RESULTS: Anxiety decreased in the intervention group following implementation of
      the orientated tour (P = 0.024). Following the orientated tour in the
      intervention group, respiration rate (P < 0.000) and blood pressure (P < 0.001
      systolic and diastolic) were significantly reduced, while heart rate and body
      temperature were not significantly different to pre-intervention. Comparison
      changes of vital signs following the orientated tour between the two groups was
      not significant. CONCLUSION: Implementation of an orientated tour of the
      preoperative room can decrease anxiety levels in children before elective
      surgeries, but it has no clinical effect on vital signs.

PMID- 24460598
TI  - Socioeconomic determinants of infant growth: The Perspective Cohort Study of Thai
      Children.
AB  - AIM:   The present study is based on the Prospective Cohort Study of Thai
      Children (PCTC), and focuses on socioeconomic factors including maternal age,
      maternal education, living with parents, family size, family income, locality,
      and sex that affect the growth outcomes of infants at 1 year of age. METHODS:  
      Data was collected among 3679 pairs of mothers and infants in the PCTC cohort in
      rural and urban locations during 2001-2002. Data collection was performed by
      interviewing mothers in their 7th to 8th month of pregnancy using family profile
      questionnaires. The anthropometric measures including weight, length, and head
      circumference of the infants were later collected at 1 year of age at home.
      RESULTS:   The results show the effects of family socioeconomic status maternal
      education, living with parents, family size, family income, locality, and sex on
      their weight (R(2) = 14.2%, P < 0.001) and length (R(2) = 8.7%, P < 0.001) at 1
      year of age. The findings suggest that maternal age, maternal education, living
      with parents, family size, family income, locality, and sex predict infant head
      circumference (R(2) = 16.8%, P < 0.001) at 1 year of age. CONCLUSION:   Infants'
      growth, including weight, height, and head circumference, are affected by family
      socioeconomic status factors. It is recommended that the effect of maternal age
      on growth and development of children among those in the PCTC cohort is examined
      in the future.

PMID- 24460599
TI  - Effect of psychosocial factors on metabolic syndrome in male and female blue
      collar workers.
AB  - AIM: The purposes of this study were to examine the relationship between
      psychosocial factors and metabolic syndrome among male and female blue-collar
      workers, and which factors influence their metabolic syndrome by sex. METHODS: A
      cross-sectional study was completed of 154 men and 80 women working at small
      companies in Korea. The data were collected through a structured questionnaire,
      blood test, and anthropometric and blood pressure measure. Metabolic syndrome was
      diagnosed from the results of blood test and the measurements of waist
      circumference and blood pressure. RESULTS: The prevalence of metabolic syndrome
      among male and female blue-collar workers was 24.0% and 7.5%, respectively.
      Multiple logistic regression analysis was performed to examine factors of
      metabolic syndrome associated with sex. After controlling for age, marital
      status, smoking, alcohol drinking, shift work, overtime work, and physical
      exercise, job stress (odds ratio [OR] = 3.10, P = 0.005) and risk perception (OR
      = 1.12, P = 0.016) were influencing factors for men, and low job stress (OR =
      0.05, P = 0.04), low social support (OR = 1.51, P = 0.009), and risk perception
      (OR = 1.27, P = 0.023) for women. CONCLUSION: Metabolic syndrome among blue
      collar workers is closely related to psychosocial factors, such as job stress,
      social support, and risk perception, with the effect of job stress a point of
      difference between men and women. Occupational health nurses should be cognizant
      of the importance of assessing the effect of psychosocial factors on
      cardiovascular risk for blue-collar workers.

PMID- 24460600
TI  - Effects of community-based case management by visiting nurses for low-income
      patients with hypertension in South Korea.
AB  - AIM: To assess the effects of a visiting nurse-driven community-based case
      management program for low-income adults with hypertension. METHODS: This single
      group pretest-post-test study included 22 newly registered low-income adult
      patients with hypertension in a public health center in Seoul. Visiting nurses
      delivered a case management program for 2-8 months. Pretest and post-test
      measurements of blood pressure (BP), knowledge level, and self-management level
      in terms of diet, lifestyle, physical activity, and medication were obtained.
      RESULTS: The visiting nurse-driven case management was effective in reducing the
      BP level and improving the knowledge and self-management level of the low-income
      adults with hypertension in the community. CONCLUSION: This study serves as a
      baseline for visiting nurse-driven case management for low-income patients with
      hypertension. Its findings suggest that visiting nurse-driven case management
      targeting the self management of BP can foster improved BP control for newly
      diagnosed hypertensive patients in low-income populations.

PMID- 24460601
TI  - Evaluation of a peer-based mental health support program for adolescents orphaned
      by AIDS in South Africa.
AB  - AIM: This article provides the findings of a qualitative study done to evaluate
      the effectiveness of a peer-based mental health support program for adolescents
      orphaned by AIDS in South Africa known as BAR, an acronym for "Better Accept
      Reality". METHODS: Data was collected from 15 adolescents orphaned by AIDS using
      focus group discussions, reflective diaries, and recordings of the adolescents'
      school grades. Data were analyzed using Colaizzi's steps of data analysis.
      RESULTS: The results showed a notable positive change in the participants'
      attitude to caregivers, responsibility to self and to others, and school grades.
      CONCLUSION: The study demonstrated that the peer-based mental health support
      program is effective in meeting the mental health needs of adolescents orphaned
      by AIDS. The participants were able to express their needs and improve
      relationships with caregivers, a clear sign of adapting to their loss.

PMID- 24460602
TI  - Factors affecting quality of life in Korean patients with chronic heart failure.
AB  - AIM: Poor health-related quality of life (HRQOL) in patients with chronic heart
      failure (CHF) may be one of the most common predictors of mortality and
      rehospitalization. This study was conducted to identify factors affecting HRQOL
      in Korean patients with CHF using two HRQOL measurements. METHODS: The study
      included a sample of 114 patients. HRQOL was measured by the Minnesota Living
      with Heart Failure Questionnaire (MLHFQ) and the World Health Organization's
      Quality of Life Instrument - Short Version (WHOQOL-BREF). Multiple regression
      analyses were performed to analyze the relationship between the factors and
      HRQOL. RESULTS: Significant correlations were found between MLHFQ and WHOQOL-BREF
      in total and component scores, with the two exceptions of WHOQOL-BREF
      psychological and MLHFQ physical or total. The perceived economic status,
      functional status, and sex were factors identified as having an effect on HRQOL.
      CONCLUSION: The MLHFQ was better able to differentiate sex, comorbidity, and
      functional status. Further studies are needed to implement cost-effective nursing
      interventions for patients with CHF to improve their HRQOL.

PMID- 24460603
TI  - Seeking a progressive relationship for learning: A theoretical scheme about the
      continuity of the student-educator relationship in clinical nursing education.
AB  - AIM: The student-educator relationship is an educational tool in nursing
      education and has long-lasting influence on the professional development of
      nursing students. Currently, this relationship in clinical settings is different
      from that in the past due to a paradigm shift in nursing education and its
      emphasis on the centrality of the relationship. METHODS: The purpose of this
      grounded theory study was to explore the continuity of the student-educator
      relationship in the Iranian context of clinical nursing education. Ten bachelor
      nursing students and 10 clinical educators at Mashhad University of Medical
      Sciences, Iran, were selected through purposive and theoretical sampling. The
      data were collected through semi-structured interviews and participant
      observation. Interviews were transcribed verbatim, and data analysis was done
      through open, axial, and selective coding, using MAXQDA ver. 2007 qualitative
      data analysis software. RESULTS: The core category emerging from the data
      analysis was "seeking a progressive relationship for learning". Other major
      categories linked to and embraced within this core category were: "creating
      emotional connection", "trying to continue the relationship chain", and "adapting
      the behaviors". CONCLUSION: The findings indicated that in the Iranian
      sociocultural context, students and educators gain some action/interaction
      strategies for continuity of their relationship. It is obvious that the role of
      the nursing clinical educators and their relationship skills are critical in the
      relationship continuity of clinical settings.

PMID- 24460606
TI  - Strengths and weaknesses of a new mouse model of thrombosis induced by inferior
      vena cava stenosis: communication from the SSC of the ISTH.

PMID- 24460607
TI  - Recurrent Mycobacterium haemophilum in a renal transplant recipient.
AB  - Mycobacterium haemophilum is a rare isolate of non-tuberculous Mycobacterium
      which has been reported to affect immunocompromised patients. We report a case of
      a 32-year-old renal transplant patient with M.  haemophilum infection initially
      involving his left sinus which was treated with appropriate antimicrobial therapy
      for thirteen months. Two weeks after cessation of antibiotics the infection
      rapidly recurred in his skin and soft tissues of his hands and feet. This case
      highlights the difficult diagnostic and therapeutic implications of atypical
      infections in transplant patients. To our knowledge this is the first reported
      case of relapsed M.  haemophilum infection in a renal transplant recipient.

PMID- 24460605
TI  - Intermittent versus continuous androgen deprivation for locally advanced,
      recurrent or metastatic prostate cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Prostate cancer is the most common cancer in older men in the United
      States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most
      cases, the first-line of treatment for these cases. The negative impact of CAD in
      quality of life, secondary to the adverse events of sustained hormone
      deprivation, plus the costs of this therapy, motivated the intermittent treatment
      approach. The objective of this study is to to perform a systematic review and
      meta-analysis of all randomized controlled trials that compared the efficacy and
      adverse events profile of intermittent versus continuous androgen deprivation for
      locally advanced, recurrent or metastatic hormone-sensitive prostate cancer.
      METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and
      CENTRAL. The endpoints were overall survival (OS), cancer-specific survival
      (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis
      (MA) of the published data. The results were expressed as Hazard Ratio (HR) or
      Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%).
      RESULTS: The final analysis included 13 trials comprising 6,419 patients with
      hormone-sensitive prostate cancer. TTP was similar in patients who received
      intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD)
      (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also
      similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95%
      = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18;
      p = 0.26). CONCLUSION: Overall survival was similar between IAD and CAD in
      patients with locally advanced, recurrent or metastatic hormone-sensitive
      prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome
      remain uncertain. Impact in QoL was similar for both groups, however, sexual
      activity scores were higher and the incidence of hot flushes was lower in
      patients treated with IAD.

PMID- 24460608
TI  - Hypericin as a marker for determination of myocardial viability in a rat model of
      myocardial infarction.
AB  - The aim of this study was to investigate the necrosis-avid agent hypericin as a
      potential indicator for determination of myocardial infarction (MI). Male Sprague
      Dawley rats (n = 30) weighing 350 +/- 20 g were subjected to acute reperfused MI.
      Animals were divided into four groups (n = 6), in which hypericin was
      intravenously injected at 0, 1, 2 and 5 mg kg(-1) respectively. One day after
      injection, rats were euthanized with their hearts excised for qualitative and
      quantitative studies by means of microscopic fluorescence examination to decide
      the dosage of hypericin. Another group was injected with hypericin at the decided
      dose and evaluated by fluorescence macroscopy in colocalization with
      triphenyltetrazoliumchloride (TTC) and histomorphology. Infarct-to-normal
      contrast ratio and relative infarct size were quantified. Hypericin-induced red
      fluorescence was significantly brighter in necrotic than in viable myocardium as
      proven by a six times higher mean fluorescence density. Mean MI area was 35.66 +/
      22.88% by hypericin fluorescence and 32.73 +/- 21.98% by TTC staining (R(2) =
      0.9803). Global MI-volume was 34.56 +/- 21.07% by hypericin and 35.11 +/- 20.47%
      by TTC staining (R(2) = 0.9933). The results confirm that hypericin specifically
      labeled necrosis, and enhanced the imaging contrast between the infarcted and
      normal myocardium, suggesting its potential applications for the assessment of
      myocardial viability.

PMID- 24460610
TI  - Battle for the planet of the apps.

PMID- 24460609
TI  - beta-alanine suppresses malignant breast epithelial cell aggressiveness through
      alterations in metabolism and cellular acidity in vitro.
AB  - BACKGROUND: Deregulated energetics is a property of most cancer cells. This
      phenomenon, known as the Warburg Effect or aerobic glycolysis, is characterized
      by increased glucose uptake, lactate export and extracellular acidification, even
      in the presence of oxygen. beta-alanine is a non-essential amino acid that has
      previously been shown to be metabolized into carnosine, which functions as an
      intracellular buffer. Because of this buffering capacity, we investigated the
      effects of beta-alanine on the metabolic cancerous phenotype. METHODS: Non
      malignant MCF-10a and malignant MCF-7 breast epithelial cells were treated with
      beta-alanine at 100 mM for 24 hours. Aerobic glycolysis was quantified by
      measuring extracellular acidification rate (ECAR) and oxidative metabolism was
      quantified by measuring oxygen consumption rate (OCR). mRNA of metabolism-related
      genes was quantified by qRT-PCR with corresponding protein expression quantified
      by immunoblotting, or by flow cytometry which was verified by confocal
      microscopy. Mitochondrial content was quantified using a mitochondria-specific
      dye and measured by flow cytometry. RESULTS: Cells treated with beta-alanine
      displayed significantly suppressed basal and peak ECAR (aerobic glycolysis), with
      simultaneous increase in glucose transporter 1 (GLUT1). Additionally, cells
      treated with beta-alanine exhibited significantly reduced basal and peak OCR
      (oxidative metabolism), which was accompanied by reduction in mitochondrial
      content with subsequent suppression of genes which promote mitochondrial
      biosynthesis. Suppression of glycolytic and oxidative metabolism by beta-alanine
      resulted in the reduction of total metabolic rate, although cell viability was
      not affected. Because beta-alanine treatment reduces extracellular acidity, a
      constituent of the invasive microenvironment that promotes progression, we
      investigated the effect of beta-alanine on breast cell viability and migration.
      beta-alanine was shown to reduce both cell migration and proliferation without
      acting in a cytotoxic fashion. Moreover, beta-alanine significantly increased
      malignant cell sensitivity to doxorubicin, suggesting a potential role as a co
      therapeutic agent. CONCLUSION: Taken together, our results suggest that beta
      alanine may elicit several anti-tumor effects. Our observations support the need
      for further investigation into the mechanism(s) of action and specificity of beta
      alanine as a co-therapeutic agent in the treatment of breast tumors.

PMID- 24460611
TI  - H7N9 influenza and beyond: international political frameworks.

PMID- 24460612
TI  - Lipid-lowering drug therapies and chronic obstructive pulmonary disease: lung
      failure or just heart failure?

PMID- 24460613
TI  - The very first requirement of treatment is that it should do no harm, so why are
      antibiotics still overprescribed?

PMID- 24460614
TI  - How to identify, assess and utilise mobile medical applications in clinical
      practice.
AB  - BACKGROUND: There are thousands of medical applications for mobile devices
      targeting use by healthcare professionals. However, several factors related to
      the structure of the existing market for medical applications create significant
      barriers preventing practitioners from effectively identifying mobile medical
      applications for individual professional use. AIMS: To define existing market
      factors relevant to selection of medical applications and describe a framework to
      empower clinicians to identify, assess and utilise mobile medical applications in
      their own practice. MATERIALS AND METHODS: Resources available on the Internet
      regarding mobile medical applications, guidelines and published research on
      mobile medical applications. RESULTS: Mobile application stores (e.g. iTunes,
      Google Play) are not effective means of identifying mobile medical applications.
      Users of mobile devices that desire to implement mobile medical applications into
      practice need to carefully assess individual applications prior to utilisation.
      DISCUSSION: Searching and identifying mobile medical applications requires
      clinicians to utilise multiple references to determine what application is best
      for their individual practice methods. This can be done with a cursory
      exploration of mobile application stores and then moving onto other available
      resources published in the literature or through Internet resources (e.g. blogs,
      medical websites, social media). Clinicians must also take steps to ensure that
      an identified mobile application can be integrated into practice after carefully
      reviewing it themselves. CONCLUSION: Clinicians seeking to identify mobile
      medical application for use in their individual practice should use a combination
      of app stores, published literature, web-based resources, and personal review to
      ensure safe and appropriate use.

PMID- 24460615
TI  - Indirect treatment comparison between fixed-dose-combinations of
      amlodipine/losartan and amlodipine/valsartan in blood pressure control.
AB  - AIMS: This study compared blood pressure (BP) changes after 8 weeks of therapy
      between a fixed-dose combination (FDC) of amlodipine/losartan and
      amlodipine/valsartan using a network meta-analysis because no trials directly
      compared amlodipine/losartan with other FDCs. METHODS: A systematic search
      identified six randomised controlled trials (amlodipine/losartan-3,
      amlodipine/valsartan-3) of FDCs and their component monotherapies. Conventional
      fixed-effects methods were used to conduct the comparisons. The primary and
      secondary effect measures were the changes in sitting diastolic and systolic
      blood pressure (sitDBP, sitSBP) at 8 weeks post-randomisation. RESULTS: The
      estimated amlodipine/valsartan - amlodipine/losartan difference (95% confidence
      interval) in sitDBP reduction was -1.27 mmHg, (-5.7, 2.2) for lower dosages and 
      0.45 mmHg, (-3.7, 2.7) for higher dosages; for sitSBP, the values were -3.74
      mmHg, (-9.0, 2.9) for lower dosages and 0.2 mmHg, (-6.2, 6.0) for higher dosages.
      The confidence of a greater reduction in BP (fixed difference = 0) on
      amlodipine/losartan 5/50 than on amlodipine/valsartan 5/80 was 77% for sitDBP and
      89% for sitSBP. The corresponding confidence for the higher doses was 61% for
      sitDBP and 48% for sitSBP. The findings support asserting with (fixed) 95%
      confidence that the BP reduction on amlodipine/valsartan 5/80 exceeds the
      amlodipine/losartan 5/50 reduction by at most 1.6 mmHg for sitDBP, and at most
      1.26 mmHg for sitSBP. The corresponding upper bounds for the higher dosages were
      2.31 mmHg (sitDBP) and 5.38 mmHg (sitSBP). CONCLUSIONS: The BP lowering effect
      with amlodipine/losartan and amlodipine/valsartan was comparable. Potential
      superiority of the reductions realised with amlodipine/valsartan relative to
      amlodipine/losartan, are unlikely to be clinically material.

PMID- 24460616
TI  - H7N9 influenza: old and new challenge.

PMID- 24460617
TI  - Assessment of aortic arch stiffness using pulse-wave tissue Doppler imaging: a
      transesophageal echocardiographic comparison study of acute ischemic stroke
      patients and stroke-free patients.
AB  - BACKGROUND: Elevated aortic stiffness determined by transesophageal
      echocardiography (TEE), and presence of complicated aortic plaque provide
      prognostic information about cerebrovascular disease risk. Recently, pulse-wave
      tissue Doppler imaging (PW-TDI) has offered a new technique for assessing aortic
      wall stiffness. METHODS: The following aortic long-axis view TEE measurements
      were carried out in 103 consecutive acute ischemic stroke patients and 72
      controls (stroke-free patients requiring TEE for conditions such as atrial
      fibrillation and valvular heart disease): (a) PW-TDI motion velocities measured
      as expansion peak velocity during systole (Vs) and contraction peak velocity
      during diastole (Vd); (b) aortic arch stiffness parameter beta (Aobeta), defined
      as beta = ln (systolic blood pressure/diastolic blood pressure)/([Dmax -
      Dmin]/Dmin), where ln is the natural logarithm, Dmax is maximum aortic lumen
      diameter, and Dmin is minimum aortic lumen diameter. The PW-TDI of Vs and Vd was
      compared with conventional vessel parameters brachial-ankle pulse wave velocity
      (baPWV) and cardio-ankle vascular index (CAVI, calculated from blood pressure and
      PWV). RESULTS: Comparing acute ischemic stroke patients versus controls, Vs and
      Vd were significantly decreased (3.3 +/- 1.6 vs. 3.9 +/- 2.0 cm/sec, P < 0.05;
      1.7 +/- 0.6 vs. 2.1 +/- 0.8 cm/sec, P < 0.01, respectively), and Aobeta and
      aortic arch intima-media thickness (AoIMT) were significantly increased (15.3 +/-
      12.5 vs. 11.6 +/- 6.5, P < 0.05; 3.2 +/- 2.5 vs. 2.4 +/- 2.1 mm, P < 0.05;
      respectively). Furthermore, Vs and Vd were significantly negatively correlated
      with age, Aobeta, AoIMT, CAVI, and baPWV in all cases. CONCLUSIONS: The use of
      aortic arch wall PW-TDI for Vs and Vd evaluation constitutes an easily and
      readily assessed parameter for evaluating aortic arch stiffness.

PMID- 24460618
TI  - Enlightened Mannhemia haemolytica lung inflammation in bovinized mice.
AB  - Polymorphonuclear cells diapedesis has an important contribution to the induced
      Mannhemia haemolytica (M. haemolytica) infection lung inflammation and IL-8 is
      the primary polymorphonuclear chemoattractant. Using a bovine IL-8/luciferase
      transiently transgenized mouse model, the orchestration among M. haemolytica, IL
      8 promoter activation and neutrophilia was followed in real time by in vivo image
      analysis. 

PMID- 24460619
TI  - Waiting to see the specialist: patient and provider characteristics of wait times
      from primary to specialty care.
AB  - BACKGROUND: Wait times are an important measure of access to various health care
      sectors and from a patient's perspective include several stages in their care.
      While mechanisms to improve wait times from specialty care have been developed
      across Canada, little is known about wait times from primary to specialty care.
      Our objectives were to calculate the wait times from when a referral is made by a
      family physician (FP) to when a patient sees a specialist physician and examine
      patient and provider factors related to these wait times. METHODS: Our study used
      the Electronic Medical Record Administrative data Linked Database (EMRALD) which
      is a linkage of FP electronic medical record (EMR) data to the Ontario, Canada
      administrative data. The EMR referral date was linked to the administrative
      physician claims date to calculate the wait times. Patient age, sex,
      socioeconomic status, comorbidity and FP continuity of care and physician age,
      sex, practice location, practice size and participation in a primary care
      delivery model were examined with respect to wait times. RESULTS: The median
      waits from medical specialists ranged from 39 to 76 days and for surgical
      specialists from 33 days to 66 days. With a few exceptions, patient factors were
      not associated with wait times from primary care to specialty care. Similarly
      physician factors were not consistently associated with wait times, except for FP
      practice location and size. CONCLUSIONS: Actual wait times for a referral from a
      FP to seeing a specialist physician are longer than those reported by physician
      surveys. Wait times from primary to specialty care need to be included in the
      calculation of surgical and diagnostic wait time benchmarks in Canada.

PMID- 24460621
TI  - Transanal dearterialization with targeted mucopexy is effective for advanced
      haemorrhoids.
AB  - AIM: Transanal haemorrhoidal dearterialization (THD) has become well established
      for the treatment of haemorrhoids. In this study we describe a technical
      modification of this technique, targeted mucopexy (THD TM), and report the
      results for advanced haemorrhoids. METHOD: The study included a prospective
      evaluation of patients with Grade IV (fourth-degree) haemorrhoids operated on
      with the THD TM technique. This consisted of an initial dearterialization when
      the haemorrhoidal arteries were transfixed and a second phase of mucopexy, using
      a different needle from that usually used in the original technique. RESULTS:
      From January 2007 to December 2011, 31 consecutive patients with Grade IV
      haemorrhoids were operated on using the THD TM technique. Postoperative pain was
      reported by 22 (70%) patients on day 1 and 19 (61%) on day 7, while nine (30%)
      did not experience any pain at all. Severe pain was reported by only nine (16%)
      patients. At a mean follow-up of 32 months, two (6.4%) patients required a
      further intervention for on-going symptoms. CONCLUSION: Transanal haemorrhoidal
      dearterialization TM is effective for advanced haemorrhoids.

PMID- 24460623
TI  - A novel optic nerve photograph alignment and subtraction technique for the
      detection of structural progression in glaucoma.
AB  - PURPOSE: To highlight changing features over time within a single static image
      through the auto-alignment and subtraction of serial optic nerve photographs.
      METHODS: Subtraction maps were generated from auto-aligned (EyeIC, Narbeth, PA)
      baseline and follow-up images using Adobe Photoshop software. They demonstrated
      progressive retinal nerve fibre layer (RNFL) defects, optic disc haemorrhage
      (DH), neuroretinal rim loss (RL) and peripapillary atrophy (PPA). A masked
      glaucoma specialist identified features of progression on subtraction map first,
      then assessed feature strength by comparison with original images using
      alternation flicker. Control images with no progression and parallax-only images
      (as determined by flicker) were included. RESULTS: Eighty eyes of 67 patients
      were used to generate subtraction maps that detected glaucoma progression in 87%
      of DH (n = 28, sensitivity (Se) 82%, specificity (Sp) 98%) and 84% of PPA (n =
      30, Se 80%, Sp 98%) cases. The lowest rate of detection was seen with RL at 67%
      (n = 31, Se 65%, Sp 100%). The subtraction technique was most sensitive for
      detecting parallax (n = 39, Se 98%, Sp 94%). Features of glaucoma progression
      appeared equally strong in flicker and subtraction images, but parallax was often
      enhanced on subtraction maps. Among control images selected for absence of
      features of glaucomatous change (n = 9) in original flicker images, no features
      were detected on subtraction maps. CONCLUSIONS: Auto-alignment and subtraction of
      serial optic nerve photographs reliably detects features of glaucoma progression
      with a single static image. Parallax identification may also be facilitated. Auto
      alignment and subtraction of serial optic nerve photographs may prove especially
      useful in education and printed publications when dynamic imaging is not
      feasible.

PMID- 24460622
TI  - Spousal diabetes as a diabetes risk factor: a systematic review and meta
      analysis.
AB  - BACKGROUND: Diabetes history in biologically-related individuals increases
      diabetes risk. We assessed diabetes concordance in spouses (that is, biologically
      unrelated family members) to gauge the importance of socioenvironmental factors.
      METHODS: We selected cross-sectional, case-control and cohort studies examining
      spousal association for diabetes and/or prediabetes (impaired fasting glucose or
      impaired glucose tolerance), indexed in Medline, Embase or Scopus (1 January 1997
      to 28 February 2013). Effect estimates (that is, odds ratios, incidence rate
      ratios, and so on) with body mass index (BMI) adjustment were pooled separately
      from those without BMI adjustment (random effects models) to distinguish BMI
      dependent and independent concordance. RESULTS: Searches yielded 2,705 articles;
      six were retained (n = 75,498 couples) for systematic review and five for meta
      analysis. Concordance was lowest in a study that relied on women's reports of
      diabetes in themselves and their spouses (effect estimate 1.1, 95% CI 1.0 to
      1.30) and highest in a study with systematic assessment of glucose tolerance
      (2.11, 95% CI 1.74 to 5.10). The random-effects pooled estimate adjusted for age
      and other covariates but not BMI was 1.26 (95% CI 1.08 to 1.45). The estimate
      with BMI adjustment was lower (1.18, 95% CI 0.97 to 1.40). Two studies assessing
      between-spouse associations of diabetes/prediabetes determined by glucose testing
      reported high concordance (OR 1.92, 95% CI 1.55 to 2.37 without BMI adjustment;
      2.32, 95% CI 1.87 to 3.98 with BMI adjustment). Two studies did not distinguish
      type 1 and type 2 diabetes. However given that around 95% of adults is type 2,
      this is unlikely to have influenced the results. CONCLUSIONS: Our pooled estimate
      suggests that a spousal history of diabetes is associated with a 26% diabetes
      risk increase. Recognizing shared risk between spouses may improve diabetes
      detection and motivate couples to increase collaborative efforts to optimize
      eating and physical activity habits.

PMID- 24460625
TI  - Unfair: government-approved sexual medicine treatments only available for men.

PMID- 24460624
TI  - PcrG protects the two long helical oligomerization domains of PcrV, by an
      interaction mediated by the intramolecular coiled-coil region of PcrG.
AB  - BACKGROUND: PcrV is a hydrophilic translocator of type three secretion system
      (TTSS) and a structural component of the functional translocon. C-terminal helix
      of PcrV is essential for its oligomerization at the needle tip. Conformational
      changes within PcrV regulate the effector translocation. PcrG is a cytoplasmic
      regulator of TTSS and forms a high affinity complex with PcrV. C-terminal
      residues of PcrG control the effector secretion. RESULT: Both PcrV and PcrG-PcrV
      complex exhibit elongated conformation like their close homologs LcrV and LcrG
      LcrV complex. The homology model of PcrV depicts a dumbbell shaped structure with
      N and C-terminal globular domains. The grip of the dumbbell is formed by two long
      helices (helix-7 and 12), which show high level of conservation both structurally
      and evolutionary. PcrG specifically protects a region of PcrV extending from
      helix-12 to helix-7, and encompassing the C-terminal globular domain. This
      fragment ?PcrV(128-294) interacts with PcrG with high affinity, comparable to the
      wild type interaction. Deletion of N-terminal globular domain leads to the
      oligomerization of PcrV, but PcrG restores the monomeric state of PcrV by forming
      a heterodimeric complex. The N-terminal globular domain (?PcrV(1-127)) does not
      interact with PcrG but maintains its monomeric state. Interaction affinities of
      various domains of PcrV with PcrG illustrates that helix-12 is the key mediator
      of PcrG-PcrV interaction, supported by helix-7. Bioinformatic analysis and study
      with our deletion mutant ?PcrG(13-72) revealed that the first predicted
      intramolecular coiled-coil domain of PcrG contains the PcrV interaction site.
      However, 12 N-terminal amino acids of PcrG play an indirect role in PcrG-PcrV
      interaction, as their deletion causes 40-fold reduction in binding affinity and
      changes the kinetic parameters of interaction. ?PcrG(13-72) fits within the
      groove formed between the two globular domains of PcrV, through hydrophobic
      interaction. CONCLUSION: PcrG interacts with PcrV through its intramolecular
      coiled-coil region and masks the domains responsible for oligomerization of PcrV
      at the needle tip. Also, PcrG could restore the monomeric state of oligomeric
      PcrV. Therefore, PcrG prevents the premature oligomerization of PcrV and
      maintains its functional state within the bacterial cytoplasm, which is a pre
      requisite for formation of the functional translocon.

PMID- 24460627
TI  - Lack of sexual privacy affects psychological and marital domains of male sexual
      dysfunction.
AB  - INTRODUCTION: Sexual dysfunctions (SDs) are dictated by predisposing,
      precipitating, maintaining, and contextual factors, the latter of which can help
      sexual problems to emerge. Even if the lack of sexual privacy is one of the most
      common contextual issues, it has not been extensively studied. AIM: Investigation
      of sexual privacy in a large sample of men consulting for SD was the aim of this
      study. METHODS: A consecutive series of 3,736 men, attending the outpatient
      clinic for SD for the first time, was retrospectively studied. Privacy during
      sexual intercourse was investigated with the following question, "During the last
      three months, have you had enough privacy during your sexual activity?" and rated
      0 = yes, 1 = sometimes, 2 = rarely, and 3 = never. MAIN OUTCOME MEASURES: Several
      clinical, biochemical, and psychological (Middlesex Hospital Questionnaire [MHQ])
      parameters were studied. RESULTS: Among the 3,736 patients studied, 83.9%
      reported enough privacy during sexual intercourse, while 8.6%, 5.7%, and 1.7%
      declared a decrease of sexual privacy of increasing severity. Lack of sexual
      privacy was associated with ejaculatory dysfunctions and with the inability to
      maintain an erection during intercourse. Subjects reporting lack of sexual
      privacy had a higher risk of relational and intrapsychic impairments, as well as
      psychopathology at MHQ questionnaire, even after adjusting for confounders.
      Fatherhood was associated with sexual privacy issues only in the lowest
      quartiles. In subjects without children, the absence of cohabitation with the
      partner was associated with an increasing risk of not having enough privacy
      (hazard ratio [HR] = 1.837 [1.269-2.659], P = 0.001); data confirmed, after
      stratification for age, only in the youngest subjects (I quartile HR = 2.159
      [1.211-3.848], P = 0.009). CONCLUSIONS: This study indicates that sexual privacy
      is often a poorly investigated item, which is important to evaluate in male SD.

PMID- 24460630
TI  - Successful treatment of renal allograft and bladder malakoplakia with
      minimization of immunosuppression and prolonged antibiotic therapy.
AB  - Malakoplakia is an unusual granulomatous inflammatory disorder associated with
      diminished bactericidal action of leucocytes that occurs in immunosuppressed
      hosts. Cases of renal allograft malakoplakia are generally associated with a poor
      graft and patient survival. We present the case of a 56-year-old female with
      allograft and bladder malakoplakia occurring two years after renal
      transplantation complicated by an early antibody mediated rejection. Following a
      number of symptomatic urinary tract infections caused by resistant Gram-negative
      bacilli, a diagnosis of malakoplakia was made by biopsy of a new mass lesion of
      the renal allograft. Cystoscopy also revealed malakoplakia of the bladder wall.
      Immunosuppressant regimen was modified. Mycophenolate mofetil was ceased,
      prednisolone reduced to 5 mg/day and tacrolimus concentrations were carefully
      monitored to maintain trough serum concentrations of 2-4 MUg/L. Concurrently, she
      received a prolonged course of intravenous antibiotics followed by 13 months of
      dual oral antibiotic therapy with fosfomycin and faropenem. This joint approach
      resulted in almost complete resolution of allograft malakoplakia lesions and
      sustained regression of bladder lesions on cystoscopy with histological
      resolution in bladder lesions. Her renal function has remained stable throughout
      the illness. If treated with sustained antimicrobial therapy and reduction of
      immunosuppression, cases of allograft malakoplakia may not necessarily be
      associated with poor graft survival. 

PMID- 24460628
TI  - Comprehensive interrogation of CpG island methylation in the gene encoding COMT,
      a key estrogen and catecholamine regulator.
AB  - BACKGROUND: The catechol-O-methyltransferase (COMT) enzyme has been widely
      studied due to its multiple roles in neurological functioning, estrogen biology,
      and methylation metabolic pathways. Numerous studies have investigated variation
      in the large COMT gene, with the majority focusing on single nucleotide
      polymorphisms (SNPs). This body of work has linked COMT genetic variation with a
      vast array of conditions, including several neurobehavioral disorders, pain
      sensitivity, and multiple human cancers. Based on COMT's numerous biological
      roles and recent studies suggesting that methylation of the COMT gene impacts
      COMT gene expression, we comprehensively interrogated methylation in over 200 CpG
      dinucleotide sequences spanning the length of the COMT gene. METHODS: Using
      saliva-derived DNA from a non-clinical sample of human subjects, we tested for
      associations between COMT CpG methylation and factors reported to interact with
      COMT genetic effects, including demographic factors and alcohol use. Finally, we
      tested associations between COMT CpG methylation state and COMT gene expression
      in breast cancer cell lines. We interrogated >200 CpGs in 13 amplicons spanning
      the 5' UTR to the last exon of the CpG dinucleotide-rich COMT gene in n = 48
      subjects, n = 11 cell lines and 1 endogenous 18S rRNA control. RESULTS: With the
      exception of the CpG island in the 5'UTR and 1st exon, all other CpG islands were
      strongly methylated with typical dynamic ranges between 50-90%. In the saliva
      samples, methylation of multiple COMT loci was associated with socioeconomic
      status or ethnicity. We found associations between methylation at numerous loci
      and genotype at the functional Val158Met SNP (rs4680), and most of the
      correlations between methylation and demographic and alcohol use factors were
      Val158Met allele-specific. Methylation at several of these loci also associated
      with COMT gene expression in breast cancer cell lines. CONCLUSIONS: We report the
      first comprehensive interrogation of COMT methylation. We corroborate previous
      findings of variation in COMT methylation with gene expression and the Val158Met
      genotype, and also report novel associations with socioeconomic status (SES) and
      ethnicity at several methylated loci. These results point to novel mechanisms for
      COMT regulation, which may have broad therapeutic implications.

PMID- 24460629
TI  - CLEC-2-dependent activation of mouse platelets is weakly inhibited by cAMP but
      not by cGMP.
AB  - BACKGROUND: The activation of platelet CLEC-2 by podoplanin on lymphatic
      endothelial cells (LECs) has a critical role in prevention of mixing of lymphatic
      and blood vasculatures during embryonic development. Paradoxically, LECs release
      cAMP and cGMP-elevating agents, prostacyclin (PGI2 ) and nitric oxide (NO),
      respectively, which are powerful inhibitors of platelet activation. This raises
      the question of how podoplanin is able to activate CLEC-2 in the presence of the
      inhibitory cyclic nucleotides. OBJECTIVES: We investigated the influence of
      cyclic nucleotides on CLEC-2 signaling in platelets. METHODS: We used rhodocytin,
      CLEC-2 monoclonal antibody, LECs and recombinant podoplanin as CLEC-2 agonists on
      mouse platelets. The effects of the cyclic nucleotide-elevating agents PGI2 ,
      forskolin and the NO-donor GSNO were assessed with light transmission
      aggregometry, flow cytometry, protein phosphorylation and fluorescent imaging of
      platelets on LECs. RESULTS: We show that platelet aggregation induced by CLEC-2
      agonists is resistant to GSNO but inhibited by PGI2 . The effect of PGI2 is
      mediated through decreased phosphorylation of CLEC-2, Syk and PLCgamma2. In
      contrast, adhesion and spreading of platelets on recombinant podoplanin, CLEC-2
      antibody and LECs is not affected by PGI2 and GSNO. Consistent with this, CLEC-2
      activation of Rac, which is required for platelet spreading, is not altered in
      the presence of PGI2 . CONCLUSIONS: The present results demonstrate that platelet
      adhesion and activation on CLEC-2 ligands or LECs is maintained in the presence
      of PGI2 and NO.

PMID- 24460631
TI  - Coenzyme Q10 supplementation improves metabolic parameters, liver function and
      mitochondrial respiration in rats with high doses of atorvastatin and a
      cholesterol-rich diet.
AB  - BACKGROUND: The aim of this study was to evaluate the actions of coenzyme Q10
      (CoQ10) on rats with a cholesterol-rich diet (HD) and high doses of atorvastatin
      (ATV, 0.2, 0.56 or 1.42 mg/day). METHODS: Two experiments were done, the first
      one without coenzyme Q10 supplementation. On the second experiment all groups
      received coenzyme Q10 0.57 mg/day as supplement. After a 6-week treatment animals
      were sacrificed, blood and liver were analyzed and liver mitochondria were
      isolated and its oxygen consumption was evaluated in state 3 (phosphorylating
      state) and state 4 (resting state) in order to calculate the respiratory control
      (RC). RESULTS: HD increased serum and hepatic cholesterol levels in rats with or
      without CoQ10. ATV reduced these values but CoQ10 improved even more serum and
      liver cholesterol. Triacylglycerols (TAG) were also lower in blood and liver of
      rats with ATV + CoQ10. HDL-C decreased in HD rats. Treatment with ATV maintained
      HDL-C levels. However, these values were lower in HD + CoQ10 compared to control
      diet (CD) + CoQ10. RC was lessened in liver mitochondria of HD. The
      administration of ATV increased RC. All groups supplemented with CoQ10 showed an
      increment in RC. In conclusion, the combined administration of ATV and CoQ10
      improved biochemical parameters, liver function and mitochondrial respiration in
      hypercholesterolemic rats. CONCLUSIONS: Our results suggest a potential
      beneficial effect of CoQ10 supplementation in hypercholesterolemic rats that also
      receive atorvastatin. This beneficial effect of CoQ10 must be combined with
      statin treatment in patient with high levels of cholesterol.

PMID- 24460633
TI  - Involvement of GPI-anchored lipid transfer proteins in the development of seed
      coats and pollen in Arabidopsis thaliana.
AB  - The non-specific lipid transfer proteins (nsLTPs) constitute a large protein
      family specific for plants. Proteins from the family are found in all land plants
      but have not been identified in green algae. Their in vivo functions are still
      disputed although evidence is accumulating for a role of these proteins in
      cuticle development. In a previous study, we performed a co-expression analysis
      of glycosylphosphatidylinositol (GPI)-anchored nsLTPs (LTPGs), which suggested
      that these proteins are also involved in the accumulation of suberin and
      sporopollenin. Here, we follow up the previous co-expression study by
      characterizing the phenotypes of Arabidopsis thaliana lines with insertions in
      LTPG genes. The observed phenotypes include an inability to limit tetrazolium
      salt uptake in seeds, development of hair-like structures on seeds, altered
      pollen morphologies and decreased levels of omega-hydroxy fatty acids in seed
      coats. The observed phenotypes give further support for a role in suberin and
      sporopollenin biosynthesis or deposition in A. thaliana. 

PMID- 24460634
TI  - '[I would like] a place to be alone, other than the toilet'--Children's
      perspectives on paediatric hospital care in the Netherlands.
AB  - BACKGROUND: Although it is widely recognized that children are willing, capable
      and legally entitled to be active participants in their health care, parents are
      generally invited to evaluate paediatric hospital care and services rather than
      children themselves. This is problematic because parents cannot serve as the only
      spokespersons for the perspectives and experiences of children. OBJECTIVE: To
      investigate children's experiences with and perspectives on the quality of
      hospital care and services in the Netherlands, and how they think care and
      services could be improved. DESIGN: A qualitative study incorporating different
      participatory data collection methods, including photovoice and children writing
      a letter to the chief executive of the hospital. SETTING: Paediatric departments
      of eight hospitals in the Netherlands (two teaching and six regional).
      PARTICIPANTS: Children and adolescents (n = 63) with either acute or chronic
      disorders, aged between 6 and 18 years. RESULTS: The research results provide
      insights into children's health and social well-being in hospitals. Important
      aspects of health, like being able to sleep well and nutrition that fits
      children's preferences, are structurally being neglected. CONCLUSION: The
      participatory approach brought children's ideas 'alive' and generated concrete
      areas for improvement that stimulated hospitals to take action. This demonstrates
      that participatory methods are not merely tools to gather children's views but
      can serve as vehicles for creating health-care services that more closely meet
      children's own needs and wishes.

PMID- 24460635
TI  - What is the current prevalence of diagnosed and yet to be diagnosed diabetes in
      the UK.

PMID- 24460636
TI  - Ageing and endurance training effects on quantity and quality of pulmonary
      vascular bed in healthy men.
AB  - It has recently been demonstrated that in healthy individuals, peak oxygen
      consumption is associated with a greater pulmonary capillary blood volume and a
      more distensible pulmonary circulation. Our cross-sectional study suggests that,
      in healthy men aged 20 to 60 years (n = 63), endurance sport practice (vigorous
      intensity domain of the International Physical Activity Questionnaire) is
      associated with better quantity (pulmonary capillary blood volume) and quality
      (slope of increase in lung diffusion for carbon monoxide on exercise) of the
      pulmonary vascular bed, partly counterbalancing the deleterious effects of
      ageing, which remains to be demonstrated in a prospective longitudinal design. 

PMID- 24460638
TI  - Congenital cataracts in an Ayrshire herd: a herd case report.
AB  - An Ayrshire dairy herd was investigated for occurrence of ocular abnormalities in
      new-born calves. Ophthalmic examinations were performed on all the animals in the
      herd and 26% of them were diagnosed with bilateral cataracts. Cataracts varied in
      extent and severity but the majority were restricted to the lens nucleus.
      Epidemiological analysis showed the prevalence was higher in male animals and
      lower in animals born to heifers. A family tree was designed but no genetic
      impact of dam lines was evident. Sire data was incomplete and could therefore not
      be included. Based on the information provided by the farmer there was no obvious
      environmental or nutritional cause of these cataracts. However, data records were
      incomplete and further investigation/monitoring of the herd would be needed to
      establish a cause and enable a better insight into the aetiology of this disease
      in cattle. 

PMID- 24460637
TI  - Gender differences in adiponectin levels and body composition in older adults:
      Hallym aging study.
AB  - BACKGROUND: Body composition changes with ageing can influence the adiponectin
      concentration. However, the component of body composition that is associated with
      adiponectin concentrations in older adults remains unclear. METHODS: There were
      152 males and 168 females aged 65 years or older that participated in the 2010
      Hallym Aging Study (HAS). Body composition (assessed by dual energy X-ray
      absorptiometry; DXA), anthropometric parameters and adiponectin were obtained
      from all participants. Multivariate linear regression models assessed the
      association of body fat percentage, regional muscle and bone mineral contents of
      body composition and waist/height ratio with adiponectin concentration. Age,
      albumin, testosterone concentration and metabolic parameters were considered as
      confounding factors. RESULTS: In correlation analysis, age was positively
      associated with adiponectin in males (P < 0.01), but not in females. Fasting
      glucose, albumin, arm skeletal muscle mass and bone mineral content were
      negatively associated with adiponectin in males (P < 0.05). Testosterone and leg
      bone mineral content were negatively associated with adiponectin in females (P <
      0.05). In multivariate linear regression models, body fat percentage and albumin
      (P < 0.05) were negatively associated with adiponectin, and high-density
      lipoprotein cholesterol (HDL-C) (P < 0.001) and age (P < 0.01) were positively
      associated with adiponectin in older males. In older females, the only factors
      that correlated significantly with adiponectin concentration were the homeostasis
      model assessment of insulin resistance (P < 0.001) and HDL-C (P < 0.05). The
      waist/height ratio and bone mineral content were not associated with adiponectin
      in either gender. CONCLUSION: Plasma adiponectin levels correlated negatively
      with body fat percentage in older males but not in older females. The
      differential results between older males and females suggest that certain gender
      specific mechanisms may affect the association between adiponectin and age
      related body composition changes.

PMID- 24460639
TI  - Management of colon cancer in the elderly: a population-based study.
AB  - AIM: Although the median age of patients diagnosed with colon cancer is over 70
      years, little is known about specific characteristics and management in the
      elderly. The aim of this study was to define the characteristics of colon cancer
      in elderly patients and compare the quality of preoperative assessment and
      surgery with that of younger patients undergoing surgery for colon cancer.
      METHOD: Data on 15,255 patients diagnosed with colon cancer between 2007 and 2010
      were retrieved from the Swedish National Colon Cancer Register. Of these, 12,959
      underwent surgical resection: 6141 were 75 years or older while 6818 were
      younger. The chi(2) test, Mann-Whitney U-test and univariable and multivariable
      logistic regression analyses were used for between-group comparison. RESULTS:
      Older patients were more likely to be female (54% older/48% younger) and have
      right-sided cancer (60% older/49% younger). Among patients who underwent
      resection, the elderly were less often evaluated regarding tumour stage prior to
      surgery (59% older/65% younger) and they were less often evaluated at a
      multidisciplinary team conference (26% older/34% younger). Elderly patients more
      frequently underwent emergency surgery (22% older/19% younger) despite having an
      earlier cancer stage. When adjusted for stage, fewer elderly patients underwent a
      radical curative procedure (OR for noncurative resection 1.19; 95% CI 1.06-1.33).
      CONCLUSION: Routine management of patients with colon cancer is age-dependent.
      Patients aged 75 years and older are less often completely staged and less often
      evaluated at a multidisciplinary team conference prior to surgery. Adjusted for
      stage, fewer elderly patients undergo curative resection.

PMID- 24460640
TI  - Abstracts of the 16th Annual Congress of the European Society for Sexual Medicine
      and the 12th Congress of the European Sexology Federation, Istanbul, Turkey,
      January 29-February 1, 2014.

PMID- 24460641
TI  - Hermenegildo Arruga (1886-1972): a versatile ophthalmologist who simplified
      cerclage to retinal surgery.
AB  - Hermenegildo Arruga Liro (1886-1972) was a versatile Spanish ophthalmologist who
      specialized in retinal surgery. He designed numerous surgical instruments and
      introduced significant improvements in ophthalmic surgical techniques. Thus, he
      was among the first ophthalmologists to advocate the intracapsular cataract
      extraction. Furthermore, he refined several surgical procedures such as
      dacryocystorhinostomy, corneal transplantation, evisceroenucleation and pterygium
      excision. Arruga perfected Gonin's operation and contributed significantly for
      retinal detachment surgery to be put in place. Later, he adopted the injection of
      air at the end of surgery. In the 1950s, Arruga simplified the technique of
      equatorial cerclage using a suture to encircle the equator of the eye. 

PMID- 24460642
TI  - Oral HPV infection in a clinic-based sample of Hispanic men.
AB  - BACKGROUND: Human papillomavirus (HPV) is associated to the pathogenesis of
      various cancers, such as oropharyngeal squamous cell carcinoma, which has a high
      incidence in Puerto Rican men. Despite the burden of oral cancer in Puerto Rico,
      little is known about the epidemiology of oral HPV infection, particularly in
      high-risk men. Therefore, this study is aimed at determining the prevalence of
      oral HPV infection, the genotype distribution and correlates associated with oral
      HPV infection in men of at least 16 years of age attending a sexually transmitted
      infection (STI) clinic in Puerto Rico. METHODS: A cross-sectional study
      consisting of 205 men was conducted. Participants provided a 30-second oral rinse
      and gargle with mouthwash. Following DNA extraction, HPV genotyping was performed
      in all samples using Innogenetics Line Price Assay (INNO-LiPA). A questionnaire
      was administered, which included a demographic, behavioral and a clinical
      assessment. Descriptive statistics and bivariate analysis were used to
      characterize the study sample. Variables that achieved statistical significance
      in the bivariate analysis (p < 0.05) were assessed in multivariate logistic
      regression models. RESULTS: The mean age of the study sample was 38.5 +/- 14.2
      years. Oral HPV prevalence among men was 20.0% (95.0%CI = 14.8%-26.1%) and of HPV
      type 16 was 2.4% (95.0%CI = 0.8%-5.6%). Oral HPV prevalence significantly
      increased over increasing age categories (p-trend = 0.001). Multivariate analysis
      showed that oral HPV was independently associated with number of sexual partners
      (adjusted OR = 1.02; 95%CI = 1.01-1.03) and lifetime use of cigarettes (adjusted
      OR = 3.00; 95%CI = 0.98-9.16). CONCLUSIONS: Oral HPV among the sampled men in the
      STI clinic was high, regardless of the HIV status or sexual behavior.
      Interventions in STI clinics should include screening for HPV in the oral cavity
      for the early detection and reduction of long-term consequences of oral HPV
      infection, such as oropharyngeal cancer.

PMID- 24460643
TI  - Protection of ischemic post conditioning against transient focal ischemia-induced
      brain damage is associated with inhibition of neuroinflammation via modulation of
      TLR2 and TLR4 pathways.
AB  - BACKGROUND AND PURPOSE: Ischemic postconditioning has been demonstrated to be a
      protective procedure to brain damage caused by transient focal
      ischemia/reperfusion. However, it is elusive whether the protection of
      postconditioning against brain damage and neuroinflammation is via regulating
      TLR2 and TLR4 pathways. In the present study, we examined the protection of
      ischemic postconditioning performed immediately prior to the recovery of cerebral
      blood supply on brain damage caused by various duration of ischemia and tested
      the hypothesis that its protection is via inhibition of neuroinflammation by
      modulating TLR2/TLR4 pathways. METHODS: Brain damage in rats was induced by using
      the middle cerebral artery occlusion (MCAO) model. Ischemic postconditioning
      consisting of fivecycles of ten seconds of ischemia and reperfusion was performed
      immediately following theischemic episode Theduration of administration of
      ischemic postconditioning was examined by comparing its effects on infarction
      volume, cerebral edema and neurological function in 2, 3, 4, 4.5and 6 hour
      ischemia groups. The protective mechanism of ischemic postconditioning was
      investigated by comparing its effects on apoptosis, production of the neurotoxic
      cytokine IL-1beta and the transcription and expression of TLR2, TLR4 and IRAK4 in
      the 2 and 4.5 hour ischemia groups. RESULTS: Ischemic postconditioning
      significantly attenuated cerebral infarction, cerebral edema and neurological
      dysfunction in ischemia groups of up to 4 hours duration, but not in 4.5and 6
      hour ischemia groups. It also inhibited apoptosis, production of IL-1beta,
      abnormal transcription and expression of TLR2, TLR4 and IRAK4 in the 2 hour
      ischemia group, but not in the 4.5 hour ischemia group. CONCLUSIONS: Ischemic
      postconditioning protected brain damage caused by 2, 3 and 4 hours of ischemia,
      but not by 4.5 and 6 hours of ischemia. The protection of ischemic
      postconditioning is associated with its inhibition of neuroinflammation via
      inhibition of TLR2 and TLR4 pathways.

PMID- 24460644
TI  - The multiscale backbone of the human phenotype network based on biological
      pathways.
AB  - BACKGROUND: Networks are commonly used to represent and analyze large and complex
      systems of interacting elements. In systems biology, human disease networks show
      interactions between disorders sharing common genetic background. We built
      pathway-based human phenotype network (PHPN) of over 800 physical attributes,
      diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological
      pathways. Using GWAS phenotype-to-genes associations, and pathway data from
      Reactome, we connect human traits based on the common patterns of human
      biological pathways, detecting more pleiotropic effects, and expanding previous
      studies from a gene-centric approach to that of shared cell-processes. RESULTS:
      The resulting network has a heavily right-skewed degree distribution, placing it
      in the scale-free region of the network topologies spectrum. We extract the multi
      scale information backbone of the PHPN based on the local densities of the
      network and discarding weak connection. Using a standard community detection
      algorithm, we construct phenotype modules of similar traits without applying
      expert biological knowledge. These modules can be assimilated to the disease
      classes. However, we are able to classify phenotypes according to shared biology,
      and not arbitrary disease classes. We present examples of expected clinical
      connections identified by PHPN as proof of principle. CONCLUSIONS: We unveil a
      previously uncharacterized connection between phenotype modules and discuss
      potential mechanistic connections that are obvious only in retrospect. The PHPN
      shows tremendous potential to become a useful tool both in the unveiling of the
      diseases' common biology, and in the elaboration of diagnosis and treatments.

PMID- 24460646
TI  - Immunoglobulin D myeloma: clinical features and outcome in the era of novel
      agents.
AB  - OBJECTIVES: Immunoglobulin D (IgD) multiple myeloma is an uncommon variant of the
      disease probably associated with poorer prognosis. However, data on IgD myeloma
      patients treated in the novel agent era are lacking. METHODS: To assess the
      frequency and the specific characteristics and evaluate the outcome of patients
      with IgD myeloma, we analyzed the database of the Greek Myeloma Study Group.
      RESULTS: Between January 2000 and December 2012, among the 1239 patients with
      symptomatic myeloma, 31 (2.5%) were diagnosed with IgD myeloma. The median age of
      patients with IgD myeloma was 65 yr (range 26-80 yr) versus 68 yr (range 23-96
      yr) of all others, and 84% had lambda light chain (vs. 38% of the patients with
      other subtypes). Patients with IgD myeloma presented more often with features of
      high-risk disease, that is, with advanced ISS, high LDH, significant renal
      dysfunction, and large amounts of Bence Jones proteinuria. Response to primary
      therapy was similar to other patients, although there was a trend for better
      quality of responses in patients with IgD myeloma. The median survival of these
      patients was 51.5 months versus 50.7 months for patients of other subtypes. In a
      multivariate model to adjust for differences in prognostic features, IgD myeloma
      was not associated with a different prognosis. CONCLUSION: The incidence of IgD
      myeloma is 2.5%. Although patients with IgD myeloma present more often with high
      risk features, their outcome in the era of novel agents is similar to that of
      patients with other myeloma subtypes.

PMID- 24460647
TI  - Atypical HUS associated with severe, unexpected antibody-mediated rejection post
      kidney transplant.
AB  - We present a case of an unsensitized patient with end-stage kidney disease
      secondary to atypical haemolytic uremic syndrome (aHUS) with mutations in
      CD46/MCP and CFH who developed severe, intractable antibody-mediated rejection
      (ABMR) unresponsive to therapy post kidney transplantation. There were no
      haematological features of thrombotic microangiopathy. The patient received
      standard induction therapy and after an initial fall in serum creatinine, severe
      ABMR developed in the setting of urosepsis. Despite maximal therapy with
      thymoglobulin, plasma exchange and methylprednisolone, rapid graft loss resulted
      and transplant nephrectomy was performed. Luminex at 4 weeks showed a new DSA and
      when repeated after nephrectomy showed antibodies to each of the 5 mismatched
      antigens with high MFI. The rate of recurrence of disease in patients with aHUS
      referred for transplantation is 50% and is associated with a high rate of graft
      loss. It is dependent in part on the nature of the mutation with circulating
      factors CFH and CFI more likely to cause recurrent disease than MCP which is
      highly expressed in the kidney. There is increasing interest in the role of
      complement in the development and propagation of ABMR via terminal complement
      activation. This case suggesting that dysregulation of the alternative complement
      pathway within the transplant kidney may have contributed to the severe AMR. Very
      little is known about the impact of complement dysregulation and the development
      of anti HLA antibodies however the strength of HLA antibody formation was
      prominent in this case. 

PMID- 24460645
TI  - D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized
      patients: a subanalysis of the randomized controlled MAGELLAN trial.
AB  - BACKGROUND: D-dimer concentrations have not been evaluated extensively as a
      predictor of increased venous thromboembolism (VTE) risk in acutely ill,
      hospitalized medical patients. OBJECTIVES: To analyze the relationships between D
      dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649).
      PATIENTS/METHODS: This was a multicenter, randomized, controlled trial. Patients
      aged >= 40 years, hospitalized for acute medical illnesses with risk factors for
      VTE received subcutaneous enoxaparin 40 mg once daily for 10 +/- 4 days then
      placebo up to day 35, or oral rivaroxaban 10 mg once daily for 35 +/- 4 days.
      Patients (n = 7581) were grouped by baseline D-dimer <= 2 * or > 2 * the upper
      limit of normal. VTE and major plus non-major clinically relevant bleeding were
      recorded at day 10, day 35, and between days 11 and 35. RESULTS: The frequency of
      VTE was 3.5-fold greater in patients with high D-dimer concentrations.
      Multivariate analysis showed that D-dimer was an independent predictor of the
      risk of VTE (odds ratio 2.29 [95% confidence interval 1.75-2.98]), and had a
      similar association to established risk factors for VTE, for example cancer and
      advanced age. In the high D-dimer group, rivaroxaban was non-inferior to
      enoxaparin at day 10 and, unlike the low D-dimer group, superior to placebo at
      day 35 (P < 0.001) and days 11-35 (P < 0.001). In both groups, bleeding outcomes
      favored enoxaparin/placebo. CONCLUSIONS: Elevated baseline D-dimer concentrations
      may identify acutely ill, hospitalized medical patients at high risk of VTE for
      whom extended anticoagulant prophylaxis may provide greater benefit than for
      those with low D-dimer concentrations.

PMID- 24460648
TI  - Molecular and functional characterization of allantoate amidohydrolase from
      Phaseolus vulgaris.
AB  - Allantoate degradation is an essential step for recycling purine-ring nitrogen in
      all plants, but especially in tropical legumes where the ureides allantoate and
      allantoin are the main compounds used to store and transport the nitrogen fixed
      in nodules. Two enzymes, allantoate amidohydrolase (AAH) and allantoate
      amidinohydrolase (allantoicase), could catalyze allantoate breakdown, although
      only AAH-coding sequences have been found in plant genomes, whereas allantoicase
      related sequences are restricted to animals and some microorganisms. A cDNA for
      AAH was cloned from Phaseolus vulgaris leaves. PvAAH is a single-copy gene
      encoding a polypeptide of 483 amino acids that conserves all putative AAH active
      site domains. Expression and purification of the cDNA in Nicotiana benthamiana
      showed that the cloned sequence is a true AAH protein that yields ureidoglycine
      and ammonia, with a Km of 0.46 mM for allantoate. Optimized in vitro assay,
      quantitative RT-PCR and antibodies raised to the PvAAH protein were used to study
      AAH under physiological conditions. PvAAH is ubiquitously expressed in common
      bean tissues, although the highest transcript levels were found in leaves. In
      accordance with the mRNA expression levels, the highest PvAAH activity and
      allantoate concentration also occurred in the leaves. Comparison of transcript
      levels, protein amounts and enzymatic activity in plants grown with different
      nitrogen sources and upon drought stress conditions showed that PvAAH is
      regulated at posttranscriptional level. Moreover, RNAi silencing of AAH
      expression increases allantoate levels in the transgenic hairy roots, indicating
      that AAH should be the main enzyme involved in allantoate degradation in common
      bean. 

PMID- 24460650
TI  - Complement profile in neonates of different gestational ages.
AB  - Blood levels of regulators of the complement system in preterm babies were
      reported in few studies only. The aim of this study was to set up a complement
      profile in premature and term babies focusing on the development of blood levels
      of MBL, key regulatory proteins and on classical pathway activity, which may
      allow an estimation of potential susceptibility to infection. Complement activity
      (CH50), levels of mannan-binding lectin (MBL), complement regulators (factors H
      and I, C1 inhibitor, properdin) and C3a as marker of complement activation were
      assessed in three groups of healthy newborns: (1) prematures (<=34 weeks); (2)
      late prematures (>34-<37 weeks) and (3) term neonates (>=37 weeks). CH50
      increased with gestational age with lower titres in cord blood than in day 5 post
      delivery venous blood. MBL concentrations were not significantly different among
      groups. Quantitative and functional C1 inhibitor were below adult normal range in
      prematures <34 weeks and lower in cord blood as compared to day 5. Factor I,
      factor H and properdin remained below adult values in all groups. Low C3a levels
      excluded that low complement titres were due to activation-induced consumption.
      These results demonstrate the relative immaturity of the complement system and
      its regulation, especially in premature infants.

PMID- 24460649
TI  - PPAR alpha and PPAR gamma polymorphisms as risk factors for dyslipidemia in a
      Chinese Han population.
AB  - BACKGROUND: The PPAR alpha and PPAR gamma are the key messengers responsible for
      the translation of nutritional stimuli into changes for the expression of genes,
      particularly genes involved in lipid metabolism. However, the associations
      between PPAR alpha/gamma polymorphisms and lipid serum levels in the general
      population were rarely studied, and the conclusions were conflicting. The
      objective was to investigate the associations of the PPAR alpha and PPAR gamma
      polymorphisms with dyslipidemia. METHODS: 820 subjects were randomly selected
      from the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province
      cohort populations. The logistic regression model was used to examine the
      association between these polymorphisms and dyslipidemia. SNPstats was used to
      explore the haplotype association analyses. RESULTS: In the codominant and log
      additive models, rs1800206, rs1805192 and rs3856806 were all associated with
      dyslipidemia (P < 0.005). When the most common haplotype L-G (established by
      rs1800206, rs4253778) was treated as the reference group, the V-G haplotype was
      associated with dyslipidemia (P < 0.001), higher TC and TG levels (P < 0.01).
      Moreover, when compared to Pro-C haplotype (established by rs1805192, rs3856806),
      the Pro-T, Ala-C, Ala-T haplotypes were associated with dyslipidemia (p < 0.001).
      A-T haplotype was associated with higher TC levels, (p < 0.01), and the P-T, A-C,
      A-T haplotypes were associated with higher TG levels (p < 0.01). CONCLUSIONS:
      PPAR alpha and PPAR gamma polymorphisms and haplotypes may be the genetic risk
      factors for dyslipidemia.

PMID- 24460651
TI  - CGtag: complete genomics toolkit and annotation in a cloud-based Galaxy.
AB  - BACKGROUND: Complete Genomics provides an open-source suite of command-line tools
      for the analysis of their CG-formatted mapped sequencing files. Determination of;
      for example, the functional impact of detected variants, requires annotation with
      various databases that often require command-line and/or programming experience;
      thus, limiting their use to the average research scientist. We have therefore
      implemented this CG toolkit, together with a number of annotation, visualisation
      and file manipulation tools in Galaxy called CGtag (Complete Genomics Toolkit and
      Annotation in a Cloud-based Galaxy). FINDINGS: In order to provide research
      scientists with web-based, simple and accurate analytical and visualisation
      applications for the selection of candidate mutations from Complete Genomics
      data, we have implemented the open-source Complete Genomics tool set, CGATools,
      in Galaxy. In addition we implemented some of the most popular command-line
      annotation and visualisation tools to allow research scientists to select
      candidate pathological mutations (SNV, and indels). Furthermore, we have
      developed a cloud-based public Galaxy instance to host the CGtag toolkit and
      other associated modules. CONCLUSIONS: CGtag provides a user-friendly interface
      to all research scientists wishing to select candidate variants from CG or other
      next-generation sequencing platforms' data. By using a cloud-based
      infrastructure, we can also assure sufficient and on-demand computation and
      storage resources to handle the analysis tasks. The tools are freely available
      for use from an NBIC/CTMM-TraIT (The Netherlands Bioinformatics Center/Center for
      Translational Molecular Medicine) cloud-based Galaxy instance, or can be
      installed to a local (production) Galaxy via the NBIC Galaxy tool shed.

PMID- 24460652
TI  - Risk of infection due to medical interventions via central venous catheters or
      implantable venous access port systems at the middle port of a three-way cock:
      luer lock cap vs. luer access split septum system (Q-Syte).
AB  - BACKGROUND: Many cancer patients receive a central venous catheter or port system
      prior to therapy to assure correct drug administration. Even appropriate hygienic
      intervention maintenance carries the risk of contaminating the middle port (C
      port) of a three-way cock (TWC), a risk that increases with the number of medical
      interventions. Because of the complexity of the cleaning procedure with
      disconnection and reconnection of the standard luer lock cap (referred as
      "intervention"), we compared luer lock caps with a "closed access system"
      consisting of a luer access split septum system with regard to process
      optimization (work simplification, process time), efficiency (costs) and hygiene
      (patient safety). METHODS: For determination of process optimization the workflow
      of an intervention according to the usual practice and risks was depicted in a
      process diagram. For determining the actual process costs, we analyzed use of
      material and time parameters per intervention and used the process parameters for
      programming the process into a simulation run (n = 1000) to determine the process
      costs as well as their differences (ACTUAL vs. NOMINAL) within the framework of a
      discrete event simulation.Additionally cultures were carried out at the TWC C
      ports to evaluate possible contamination. RESULTS: With the closed access system,
      the mean working time of 5.5 minutes could be reduced to 2.97 minutes. The
      results for average process costs (labour and material costs per use) were 3.92 ?
      for luer lock caps and 2.55 ? for the closed access system. The hypothesis test
      (2-sample t-test, CI 0.95, p-value<0.05) confirmed the significance of the
      result.In 50 reviewed samples (TWC's), the contamination rate for the luer lock
      cap was 8% (4 out of 50 samples were positive), the contamination rate of the 50
      samples with the closed access system was 0%.Possible hygienic risks (related to
      material, surroundings, staff handling) could be reduced by 65.38%. CONCLUSIONS:
      In the present research, the closed access system with a divided split septum was
      superior to conventional luer lock caps. The advantage of the closed access
      system lies in the simplified handling for staff, which results in a reduced risk
      of patient infection due to improved clinical hygiene.

PMID- 24460653
TI  - Cardiovascular risk factors associated with age-related macular degeneration: the
      Tromso Study.
AB  - PURPOSE: To examine associations between cardiovascular risk factors and age
      related macular degeneration (AMD). METHODS: A population-based, cross-sectional
      study of Caucasians aged 65-87 years was conducted in Norway in 2007/2008.
      Retinal photographs were graded for AMD. Multivariable logistic regression
      analyses were performed based on questionnaires addressing habits of smoking,
      alcohol consumption, physical activity, health and medication; and physical
      examination comprising anthropometric measurements, blood pressure and blood
      sampling. Cardiovascular disease status was obtained from a validated end-point
      registry. RESULTS: Gradable photographs were available for 2631 participants, of
      whom 92 (3.5%) subjects had late AMD. In the multivariable analysis of late AMD,
      significant interactions were found between sex and the variables age,
      triglyceride level, use of lipid-lowering drugs and physical exercise. Current
      daily smoking was significantly related to late AMD in both sexes (odds ratio
      (OR) 4.06, 95% confidence interval (CI) 1.69-9.76 and OR 3.59, 95% CI 1.17-11.04,
      women and men, respectively) compared with never smokers. Higher number of pack
      years was associated with the presence of large drusen (>125 MUm) (OR 1.04, 95%
      CI 1.01-1.09 per 5 years). Higher systolic blood pressure (OR 1.06, 95% CI 1.01
      1.12 per 5 mmHg), overweight (OR 2.87, 95% CI 1.13-7.29) and obesity (OR 2.92,
      95% CI 1.06-8.03), physical exercise duration (OR 0.41, 95% 0.18-0.96 for 30 min
      or more compared with less) and frequency (OR 0.46, 95% CI 0.23-0.92 for weekly
      or more often compared to less) were associated with late AMD in women only.
      CONCLUSIONS: Smoking was strongly associated with AMD, in line with results from
      other populations. Also, late AMD was related to higher systolic blood pressure,
      physical inactivity, overweight and obesity in women.

PMID- 24460654
TI  - A lectin from Spatholobus parviflorus inhibits Aspergillus flavus alpha-amylase:
      enzyme kinetics and thermodynamic studies.
AB  - Aspergillus flavus is a commonly found fungal pathogen which produces
      structurally related and highly toxic secondary metabolites, aflatoxins. It has
      been proposed that alpha-amylase inhibitors may limit the ability of the fungus
      to produce aflatoxins. Hence, this enzyme is a potent target for the development
      of antifungal agents. In this study, it was found that Spatholobus parviflorus
      seed lectin (SPL) can inhibit the growth of A. flavus with a MIC value of 1.5
      mg/mL. The enzyme kinetics, molecular modeling and isothermal titration
      calorimetric studies suggest that SPL can inhibit alpha-amylase with Ki value of
      0.0042 mm. Hence, it is suggested that the antifungal activity of SPL might be
      partly due to its ability to inhibit the enzyme alpha-amylase.

PMID- 24460655
TI  - Approaching low liver iron burden in chelated patients with non-transfusion
      dependent thalassemia: the safety profile of deferasirox.
AB  - OBJECTIVE: Patients with non-transfusion-dependent thalassemia (NTDT) often
      develop iron overload and related complications, and may require iron chelation.
      However, the risk of over-chelation emerges as patients reach low, near-normal
      body iron levels and dose adjustments may be needed. In the THALASSA study, the
      threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients
      receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was
      performed to characterize the safety profile of deferasirox as these patients
      approached LIC<3. METHODS: THALASSA was a randomized, double-blind, placebo
      controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in
      patients with NTDT. Patients randomized to deferasirox or placebo in the core
      could enter a 1-yr extension, with all patients receiving deferasirox (extension
      starting doses based on LIC at end-of-core and prior chelation response). The
      deferasirox safety profile was assessed between baseline and 6 months before
      reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3
      (Period 2). RESULTS: Mean +/- SD deferasirox treatment duration up to reaching
      LIC<3 was 476 +/- 207 d, and deferasirox dose was 9.7 +/- 3.0 mg/kg/d. The
      exposure-adjusted AE incidence regardless of causality was similar in periods 1
      (1.026) and 2 (1.012). There were no clinically relevant differences in renal and
      hepatic laboratory parameters measured close to the time of LIC<3 compared with
      measurements near the previous LIC assessment. CONCLUSIONS: The deferasirox
      safety profile remained consistent as patients approached the chelation
      interruption target, indicating that, with appropriate monitoring and dose
      adjustments in relation to iron load, low iron burdens may be reached with
      deferasirox with minimal risk of over-chelation.

PMID- 24460657
TI  - Intrinsic religiosity buffers the longitudinal effects of peer victimization on
      adolescent depressive symptoms.
AB  - Peer victimization is a common and potentially detrimental experience for many
      adolescents. However, not all youth who are exposed to peer victimization
      experience maladaptive outcomes, such as depression. Thus, greater attention to
      potential moderators of peer victimization is particularly important. The current
      study examined the potential moderating effect of intrinsic religiosity and
      religious attendance on the longitudinal association between physical and
      relational victimization and depressive symptoms. A diverse sample of adolescents
      (N = 313; M(age) = 17.13 years; 54% female; 49% Caucasian, 24% African American,
      19% Latino, 8% mixed race/other; 80% Christian religious affiliation) were
      recruited from a rural, low-income setting. Adolescents completed self-report
      measures of religious attendance and intrinsic religiosity, and two forms of
      victimization (i.e., physical and relational) were assessed using sociometric
      procedures in 11th grade. Depressive symptoms were measured in both 11th and 12th
      grade. Results suggest that relational victimization is associated prospectively
      with depressive symptoms only under conditions of adolescents' low intrinsic
      religiosity. Findings may contribute to efforts aimed at prevention and
      intervention among adolescents at risk for peer victimization and depression.

PMID- 24460656
TI  - Finding gene clusters for a replicated time course study.
AB  - BACKGROUND: Finding genes that share similar expression patterns across samples
      is an important question that is frequently asked in high-throughput microarray
      studies. Traditional clustering algorithms such as K-means clustering and
      hierarchical clustering base gene clustering directly on the observed
      measurements and do not take into account the specific experimental design under
      which the microarray data were collected. A new model-based clustering method,
      the clustering of regression models method, takes into account the specific
      design of the microarray study and bases the clustering on how genes are related
      to sample covariates. It can find useful gene clusters for studies from
      complicated study designs such as replicated time course studies. FINDINGS: In
      this paper, we applied the clustering of regression models method to data from a
      time course study of yeast on two genotypes, wild type and YOX1 mutant, each with
      two technical replicates, and compared the clustering results with K-means
      clustering. We identified gene clusters that have similar expression patterns in
      wild type yeast, two of which were missed by K-means clustering. We further
      identified gene clusters whose expression patterns were changed in YOX1 mutant
      yeast compared to wild type yeast. CONCLUSIONS: The clustering of regression
      models method can be a valuable tool for identifying genes that are coordinately
      transcribed by a common mechanism.

PMID- 24460658
TI  - Implementing and sustaining EBP in real world healthcare settings: a leader's
      role in creating a strong context for EBP.

PMID- 24460660
TI  - Australian/New Zealand Bachelor of Oral Health students: sociodemographics and
      career decisions.
AB  - This article describes the sociodemographic profile and factors affecting career
      decisions of Bachelor of Oral Health (BOH) students in Australia and New Zealand.
      Data were collected during the 2009 and 2011 academic years via online. A total
      of 271 students participated. The majority were female (87.8%), single (74.5%)
      and of Anglo-Saxon background (59.4%), and the average age was 23.7 years. The
      majority indicated that their fathers had at least secondary school education.
      The majority (52.8%) decided to study BOH after high school, and of those who
      commence after high school, 53.7% worked as a dental assistant/auxiliary. Career
      selection was self-motivated (70.2%) and a career to 'care for and help other
      people' (59.6%). Most respondents wished to work in a city (59.8%), in both the
      public and the private sectors (47.2%). This study represents a comprehensive
      assessment of BOH student profile in Australia and New Zealand. Findings indicate
      an overall different BOH student profile compared with other oral health
      profession students in Australia. A significant proportion had previous
      employment as a dental auxiliary staff and an increasing number of male students.
      Findings are relevant to educators, recruitment administrators and policy makers
      in the way the BOH profession is presented as a career option. 

PMID- 24460661
TI  - A role for everolimus in post-transplant encapsulating peritoneal sclerosis:
      first case report.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal
      dialysis (PD) that carries a high morbidity and mortality. The 'two hit theory'
      suggests that long term deterioration of the peritoneum combined with
      intraperitoneal inflammation is needed in the pathogenesis of EPS. For unclear
      reasons, post transplantation EPS is being increasingly reported in patients
      previously on PD. To date, there is no proven effective therapy with an absence
      of randomised controlled trials. Individual case reports and small case series
      have reported on the use of tamoxifen and corticosteroids for medical management
      of EPS. The use of everolimus has been reported in a single case, and never in
      the setting of renal transplantation. Here, we present the first case of post
      transplant encapsulating peritoneal sclerosis treated successfully with a
      combination of everolimus, tamoxifen, low dose corticosteroid and surgery. 

PMID- 24460662
TI  - Decision making on detection and triage of oral mucosa lesions in community
      dental practices: screening decisions and referral.
AB  - Oral cancer is a substantial, often unrecognized issue globally, with close to
      300 000 new cases reported annually. It is a management conundrum: a cancer site
      that is easily examined; yet more than 40% of oral cancers are diagnosed at a
      late stage when prognosis is poor and treatment can be devastating. Opportunistic
      screening within the dental office could lead to earlier diagnosis and
      intervention with improved survival. OBJECTIVE: To describe how clinicians make
      decisions about referral based on the risk classification of the lesion. METHODS:
      Eighteen dentists from 15 dental offices participated in a 1-day workshop on oral
      cancer screening. Participants then screened patients (medical history,
      conventional oral exam, fluorescent visualization examination) in-office for 11
      months, triaging patients by apparent clinical risk: low risk (common benign
      conditions, geographic tongue, candidiasis, trauma), intermediate risk (lichenoid
      lesions) and high risk (white or red lesions or ulcers without apparent cause).
      Clinicians made the decision on which lesions to reassess in 3 weeks based on
      risk assessment and clinical judgment. Lesions of concern were seen by a
      community facilitator or referred to an oral medicine specialist. RESULTS: Of
      2542 patients were screened, and 389 lesions were identified (15% of patients).
      350 were determined to be low risk (90%), 19 intermediate risk (IR) (5%), and 20
      high risk (HR) (5%). One hundred and sixty-six (43%) patients were recalled for 3
      week reassessment: 90% of HR lesions, 63% of IR lesions (63%), and 39% of low
      risk lesions. Compliance to recall was high (92% of cases). Reassessment
      eliminated the referral of 99/166 (60%) of lesions that had resolved. six lesions
      were biopsied with three low-grade dysplasias identified. CONCLUSIONS: Three key
      decision points were tested: risk assessment, need for reassessment, and need for
      referral. A 3-week reassessment appointment was invaluable to prevent the
      unnecessary referral due to confounders. There is a need for a well-defined
      triage pathway to facilitate oral cancer screening and a methodical and
      consistent approach to opportunistic screening in the dental office.

PMID- 24460664
TI  - Early molecular events involved in Pinus pinaster Ait. somatic embryo development
      under reduced water availability: transcriptomic and proteomic analyses.
AB  - Maritime pine somatic embryos (SEs) require a reduction in water availability
      (high gellan gum concentration in the maturation medium) to reach the
      cotyledonary stage. This key switch, reported specifically for pine species, is
      not yet well understood. To facilitate the use of somatic embryogenesis for mass
      propagation of conifers, we need a better understanding of embryo development.
      Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass
      spectrometry (MS) identification] of immature SEs, cultured on either high (9G)
      or low (4G) gellan gum concentration, was performed, together with analysis of
      water content, fresh and dry mass, endogenous abscisic acid (ABA; gas
      chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch
      and confocal laser microscope observations. This multiscale, integrated analysis
      was used to unravel early molecular and physiological events involved in SE
      development. Under unfavorable conditions (4G), the glycolytic pathway was
      enhanced, possibly in relation to cell proliferation that may be antagonistic to
      SE development. Under favorable conditions (9G), SEs adapted to culture
      constraint by activating specific protective pathways, and ABA-mediated molecular
      and physiological responses promoting embryo development. Our results suggest
      that on 9G, germin-like protein and ubiquitin-protein ligase could be used as
      predictive markers of SE development, whereas protein phosphatase 2C could be a
      biomarker for culture adaptive responses. This is the first characterization of
      early molecular mechanisms involved in the development of pine SEs following an
      increase in gellan gum concentration in the maturation medium, and it is also the
      first report on somatic embryogenesis in conifers combining transcriptomic and
      proteomic datasets. 

PMID- 24460663
TI  - Treatment seeking behaviour in southern Chinese elders with chronic orofacial
      pain: a qualitative study.
AB  - BACKGROUND: Chronic orofacial pain (OFP) is common in general adult populations
      worldwide. High levels of psychological distress and impaired coping abilities
      are common among Western people with chronic OFP but limited information was
      found in southern Chinese people. This study aimed to explore the perceptions and
      experiences of community dwelling elderly people with chronic OFP symptoms and
      their treatment seeking behaviour in Hong Kong. METHODS: An exploratory
      qualitative interview study was conducted. Elderly people experiencing chronic
      OFP symptoms were invited to take part in an individual semi-structured
      interview. A total of 25 semi-structured interviews were performed for 25
      participants. RESULTS: Pertinent issues relating to the treatment seeking
      behaviour emerged from the interviews, many of which were inter-related and
      overlapping. They were organized into three major themes: (i) Impact of chronic
      OFP on daily life; (ii) Personal knowledge and feeling of chronic OFP; (iii)
      Management of chronic OFP. The participants were found to have the intention to
      seek professional treatment, but there were barriers which discouraged them
      continuing to seek professional treatment. They also received complementary
      treatment for chronic OFP, such as acupuncture, massage and "chi kung". Moreover,
      a wide range self-management techniques were also mentioned. On the other hand,
      those who did not seek professional treatment for the chronic OFP claimed that
      they had accepted or adapted to the pain as part of their lives. CONCLUSIONS:
      This qualitative study observed that elderly people affected by chronic OFP
      symptoms in Hong Kong sought many different ways to manage their pain including
      traditional and complementary approaches. The role of the dentist in dealing with
      chronic OFP is unclear. Multiple barriers exist to accessing care for chronic
      OFP. The findings may be used to inform future chronic OFP management strategies
      in Hong Kong.

PMID- 24460665
TI  - Dental hospitalization trends in Western Australian children under the age of 15
      years: a decade of population-based study.
AB  - BACKGROUND AND AIM: This study analyzed a decade of dental admission patterns in
      Western Australian children under the age of 15 years, examining associations
      with sociodemographic characteristics and with particular focus on dental decay
      and Indigenous children. METHODS: This retrospective study analyzed the data
      obtained for 43,937 child patients under the age of 15 years hospitalized for an
      oral-health-related condition, as determined by principal diagnosis (ICD-10AM).
      Primary place of residency, age, gender, insurance status and Indigenous status
      were also analyzed. RESULTS: 'Dental caries' and 'embedded and impacted teeth'
      were the most common reasons for hospitalization among children under the age of
      15 years. 'Dental caries' were most common in non-Indigenous patients, with 'pulp
      and periapical' most prevalent in Indigenous patients. The age-standardized rate
      (ASR) of hospitalization for Indigenous children in the last decade increased to
      reach that of non-Indigenous children in 2009. Total DRG costs of
      hospitalization, both public and private, were in excess of AUS $92 million over
      10 years. CONCLUSIONS: This study indicates the burden of oral-health-related
      conditions on Western Australian children and the hospital system, in terms of
      health and economical impact.

PMID- 24460666
TI  - A semiautomatic tool for prostate segmentation in radiotherapy treatment
      planning.
AB  - BACKGROUND: Delineation of the target volume is a time-consuming task in
      radiotherapy treatment planning, yet essential for a successful treatment of
      cancers such as prostate cancer. To facilitate the delineation procedure, the
      paper proposes an intuitive approach for 3D modeling of the prostate by slice
      wise best fitting ellipses. METHODS: The proposed estimate is initialized by the
      definition of a few control points in a new patient. The method is not restricted
      to particular image modalities but assumes a smooth shape with elliptic cross
      sections of the object. A training data set of 23 patients was used to calculate
      a prior shape model. The mean shape model was evaluated based on the manual
      contour of 10 test patients. The patient records of training and test data are
      based on axial T1-weighted 3D fast-field echo (FFE) sequences. The manual
      contours were considered as the reference model. Volume overlap (Vo), accuracy
      (Ac) (both ratio, range 0-1, optimal value 1) and Hausdorff distance (HD) (mm,
      optimal value 0) were calculated as evaluation parameters. RESULTS: The median
      and median absolute deviation (MAD) between manual delineation and deformed mean
      best fitting ellipses (MBFE) was Vo (0.9 +/- 0.02), Ac (0.81 +/- 0.03) and HD
      (4.05 +/- 1.3)mm and between manual delineation and best fitting ellipses (BFE)
      was Vo (0.96 +/- 0.01), Ac (0.92 +/- 0.01) and HD (1.6 +/- 0.27)mm. Additional
      results show a moderate improvement of the MBFE results after Monte Carlo Markov
      Chain (MCMC) method. CONCLUSIONS: The results emphasize the potential of the
      proposed method of modeling the prostate by best fitting ellipses. It shows the
      robustness and reproducibility of the model. A small sample test on 8 patients
      suggest possible time saving using the model.

PMID- 24460667
TI  - Antisepsis with polyhexanide is effective against endophthalmitis after
      intravitreal injections.

PMID- 24460668
TI  - A Phase 1 dose-ranging study examining the effects of a superabsorbent polymer
      (CLP) on fluid, sodium and potassium excretion in healthy subjects.
AB  - BACKGROUND: CLP is an orally administered, non-absorbed, superabsorbent polymer
      being developed to increase fecal excretion of sodium, potassium and water in
      patients with heart failure and end-stage renal disease. This study was conducted
      to evaluate the safety of CLP, and to explore dose-related effects on fecal
      weight, fecal and urine sodium and potassium excretion, and serum electrolyte
      concentrations. METHODS: This Phase 1, open-label, dose-escalation study included
      25 healthy volunteers, who were administered CLP orally immediately prior to four
      daily meals for 9 days at doses of 7.5, 15.0, and 25.0 g/day (n = 5/group). An
      additional dose group received 15.0 g/day CLP under fasting conditions, and an
      untreated cohort (n = 5) served as control. Twenty-four-hour fecal and urinary
      output was collected daily. Samples were weighed, and sodium, potassium, and
      other ion content in stool and urine were measured for each treatment group.
      Effects on serum cation concentrations, other standard laboratory values, and
      adverse events were also determined. RESULTS: At doses below 25.0 g/day, CLP was
      well tolerated, with a low frequency of self-limiting gastrointestinal adverse
      events. CLP increased fecal weight and fecal sodium and potassium content in a
      dose-related manner. Concomitant dose-related decreases in urinary sodium and
      potassium were observed. All serum ion concentrations remained within normal
      limits. CONCLUSIONS: In this study, oral CLP removed water, sodium and potassium
      from the body via the gastrointestinal tract in a dose related fashion. CLP could
      become useful for patients with fluid overload and compromised kidney function in
      conditions such as congestive heart failure, salt sensitive hypertension, chronic
      kidney disease and end stage renal disease. TRIAL REGISTRATION: NCT01944007.

PMID- 24460669
TI  - Frequency and risk factors of musculoskeletal pain in nurses at a tertiary centre
      in Jeddah, Saudi Arabia: a cross sectional study.
AB  - BACKGROUND: Musculoskeletal complaints are an important occupational problem;
      nevertheless, few studies have targeted nurses in Saudi Arabia. The aim of this
      study was to determine the frequency and risk factors of work-related
      musculoskeletal disorders (WMSDs) among nursing personnel at a tertiary centre in
      Jeddah. METHODS: A comparative cross-sectional study was performed in which full
      time registered nurses from four different departments (n = 200) were selected
      for analysis between September 1, 2011 and February 29, 2012. Musculoskeletal
      symptoms over the past year were assessed using the Nordic Standardised
      Musculoskeletal Questionnaire. In addition to demographic questions, the
      researcher evaluated employment history, physical risk factors at work, and
      general health status. RESULTS: In this study, approximately 85% of the nurses
      reported experiencing at least one musculoskeletal symptom. Musculoskeletal
      symptoms occurred most commonly in the lower back (65.7%), ankles and feet
      (41.5%), and shoulders (29%). Prolonged working hours and being underweight were
      significantly associated with the development of these symptoms (OR 3.66, 95% CI
      1.24-10.79, P = 0.018, and OR 2.66, 95% CI 1.37-5.93, P = 0.004, respectively).
      Working in the surgical department was a greater risk factor for low back pain
      compared with working in other departments. CONCLUSIONS: WMSDs are common among
      our nurses, and back pain is the most common symptom. As prolonged working hours
      and being underweight were factors that contributed most to WMSDs, decreasing
      shift durations or offering nutrition educational programmes may be suitable
      solutions. However, further studies are required to examine the best modality for
      decreasing the occurrence of WMSDs.

PMID- 24460670
TI  - Enhanced iodine supplementation alters the immune process in a transgenic mouse
      model for autoimmune thyroiditis.
AB  - BACKGROUND: The impact of excessive iodine intake on the development of
      autoimmune thyroiditis (AIT) is still under debate. Transgenic, antibody-devoid
      TAZ10 mice spontaneously develop AIT due to autoreactive thyroperoxidase-specific
      T cells. In this model, development of AIT is determined by a T cell infiltration
      of the thyroid gland leading to an elevation of serum thyrotropin (TSH) levels
      and significant weight gain. In the present study we investigated the impact of
      moderate and high iodine supplementation on the course of disease in these mice,
      which are immunologically prone to AIT. METHODS: In addition to normal nutrition,
      mice were supplemented for 20 weeks with 2.5 MUg versus 5 MUg iodine per
      milliliter drinking water, which corresponds to a human daily iodine
      supplementation of 150 MUg, 315 MUg, and 615 MUg iodine. AIT-defining parameters
      (weight gain, elevation of serum TSH levels, cellular infiltration of the
      thyroid) and immunologic effects were analyzed. RESULTS: No significant
      differences were displayed when comparing weight and serum TSH levels in the
      iodine-supplemented versus control groups. Increased thyroid infiltrates with
      CD8+ T cells were detected by fluorescein-activated cell sorter (FACS) and
      immunofluorescence staining in mice supplemented with elevated iodine amounts
      (315 MUg and 615 MUg iodine per day, respectively). Immunologic monitoring
      revealed selective changes in immune cell frequencies (CD8+ and regulatory T
      cells, natural killer [NK] cells) and cytokine production (interferon-gamma,
      interleukin-1alpha, and interleukin-17), however, without affecting the overall
      immune balance. CONCLUSION: Our results demonstrate that elevated iodine
      supplementation has no physical impact on the course of disease in transgenic,
      antibody-devoid TAZ10 mice, which are immunologically prone to AIT.

PMID- 24460671
TI  - Lead optimization on conventional non-steroidal anti-inflammatory drugs: an
      approach to reduce gastrointestinal toxicity.
AB  - Non-steroidal anti-inflammatory drugs are among the most widely used
      therapeutics, primarily for the treatment for pain and inflammation.
      Prostaglandins mediate a number of characteristic features of the body's response
      to tissue injury or inflammation. These outstanding effects include their
      cytoprotective properties in the gastrointestinal tract and control of renal
      functions in the kidney. Non-steroidal anti-inflammatory drugs exert their anti
      inflammatory and antipyretic effects by blocking the production of prostanoids
      from arachidonic acid through inhibition ofcyclooxygenase enzyme. Classic non
      steroidal anti-inflammatory drugs such as meclofenamic acid and indomethacin
      inhibit both isoforms of cyclooxygenase non-selectively or with low selectivity,
      exerting their anti-inflammatory activity via inhibiting cyclooxygenase-2, and
      their deleterious side-effects by inhibiting cyclooxygenase-1. To provide an
      effective treatment for inflammatory disorders, the design of novel non-steroidal
      anti-inflammatory drugs is aimed at obtaining new drugs, devoid of the side
      effects commonly associated with conventional non-steroidal anti-inflammatory
      drugs. Several approaches have been explored to counteract the gastric damaging
      effects of these drugs. The chemical modification of non-steroidal anti
      inflammatory drugs is aimed at improving their safety profile, where several
      studies have described the derivatization of the carboxylate function of non
      steroidal anti-inflammatory drugs with less acidic analogs, which resulted in an
      increased anti-inflammatory activity with reduced ulcerogenicity. The present
      review explores the possible ways aimed to reduce ulcerogenicity. 

PMID- 24460672
TI  - Midkine: an emerging target of drug development for treatment of multiple
      diseases.
AB  - Midkine is a multifunctional factor and has anti-apoptotic, migration-promoting,
      angiogenic, anti-microbial and other activities. Midkine ameliorates ischemic
      injury in the heart and brain, enhances oocyte maturation, and is involved in
      neurogenesis. On the other hand, midkine is an important factor in the etiology
      of various diseases, especially those with inflammatory backgrounds. Furthermore,
      midkine is overexpressed in most malignant tumors and plays roles in their
      invasive phenotypes as well as in their resistance to chemotherapeutics.
      Therefore, midkine itself is expected to be useful for the treatment of brain and
      heart diseases, while midkine inhibitors are promising for the treatment of
      malignant tumors, multiple sclerosis, restenosis, renal diseases, hypertension
      and osteoporosis. Blood levels of midkine are also expected to be helpful as
      disease markers, especially as cancer markers. LINKED ARTICLES: This article is
      part of a themed section on Midkine. To view the other articles in this section
      visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24460673
TI  - The expression and function of midkine in the vertebrate retina.
AB  - The functional role of midkine during development, following injury and in
      disease has been studied in a variety of tissues. In this review, we summarize
      what is known about midkine in the vertebrate retina, focusing largely on recent
      studies utilizing the zebrafish (Danio rerio) as an animal model. Zebrafish are a
      valuable animal model for studying the retina, due to its very rapid development
      and amazing ability for functional neuronal regeneration following neuronal cell
      death. The zebrafish genome harbours two midkine paralogues, midkine-a (mdka) and
      midkine-b (mdkb), which, during development, are expressed in nested patterns
      among different cell types. mdka is expressed in the retinal progenitors and mdkb
      is expressed in newly post-mitotic cells. Interestingly, studies of loss- and
      gain-of-function in zebrafish larvae indicate that midkine-a regulates cell cycle
      kinetics. Moreover, both mdka and mdkb are expressed in different cell types in
      the normal adult zebrafish retina, but after light-induced death of
      photoreceptors, both are up-regulated and expressed in proliferating Muller glia
      and photoreceptor progenitors, suggesting an important and (perhaps) coincident
      role for these cytokines during stem cell-based neuronal regeneration. Based on
      its known role in other tissues and the expression and function of the midkine
      paralogues in the zebrafish retina, we propose that midkine has an important
      functional role both during development and regeneration in the retina. Further
      studies are needed to understand this role and the mechanisms that underlie it.
      LINKED ARTICLES: This article is part of a themed section on Midkine. To view the
      other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue
      4.

PMID- 24460674
TI  - Midkine in repair of the injured nervous system.
AB  - Midkine (MK) is a growth factor with neurotrophic and neurite outgrowth
      activities. It was expressed in the peri-ischaemic area in the acute phase of
      cerebral infarction in rat brains. Astrocytes were the origin of MK in this
      occasion. MK has been assessed in terms of its effects on neural injury. The
      administration of MK into the lateral ventricle immediately prior to ischaemia
      prevented cell death in the hippocampal CA1 neurons degenerated by transient
      forebrain ischaemia in gerbils. MK administration was also beneficial in rats
      with neural injury, especially after kainic acid-induced seizures. Gene therapy
      with mouse MK cDNA using an adenovirus was effective in reducing the cerebral
      infarction volume and in increasing the number of neuronal precursor cells in the
      subventricular zone of the rat brain. MK mRNA and MK protein were found in spinal
      cord motor neurons of the anterior horn in both the acute phase of sciatic nerve
      injury and 3 weeks later. MK immunoreactivity was also found in the proximal side
      of a sciatic nerve-injured site in sciatic nerve axons. MK receptors were
      expressed in Schwann cells after injury, suggesting crosstalk between axons and
      Schwann cells. MK was also present in nerve terminals and influenced ACh receptor
      clustering during neuromuscular development in Xenopus. Thus, MK may also be
      involved in reinforcing and maintaining the synapse. All these findings indicate
      the therapeutic potential of MK for promoting repair of the nervous system after
      injury. LINKED ARTICLES: This article is part of a themed section on Midkine. To
      view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24460675
TI  - Midkine and multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune neurological disease characterized by
      inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its
      animal model, experimental autoimmune encephalomyelitis (EAE), have been thought
      as autoreactive Th1 and Th17 cell-mediated diseases. CD4(+) CD25(+) FoxP3(+)
      regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and
      tolerogenic dendritic cells (DCreg) drive the development of inducible Treg
      cells. Thus, a dysfunction in the development of Treg and DCreg leads to the
      development of autoimmune diseases. However, the factors that regulate Treg and
      DCreg are largely unknown. We recently showed that removal of midkine (MK)
      suppressed EAE due to an expansion of the Treg cell population as well as a
      decrease in the numbers of autoreactive Th1 and Th17 cells. MK decreased the Treg
      cell population by suppressing the phosphorylation of STAT5, which is essential
      for the expression of Foxp3, the master transcriptional factor of Treg cell
      differentiation. Furthermore, MK reduces the DCreg cell population by inhibiting
      the phosphorylation of STAT3, which is critical for DCreg development. Blockade
      of MK signalling by a specific RNA aptamer significantly elevated the population
      of DCreg and Treg cells and ameliorated EAE without detectable adverse effects.
      Therefore, the inhibition of MK may provide an effective therapeutic strategy
      against autoimmune diseases including MS. LINKED ARTICLES: This article is part
      of a themed section on Midkine. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24460678
TI  - Opening peer-review: the democracy of science.

PMID- 24460677
TI  - Peripheral interactions between cannabinoid and opioid systems contribute to the
      antinociceptive effect of crotalphine.
AB  - BACKGROUND AND PURPOSE: Crotalphine is an antinociceptive peptide that, despite
      its opioid-like activity, does not induce some of the characteristic side effects
      of opioids, and its amino acid sequence has no homology to any known opioid
      peptide. Here, we evaluated the involvement of the peripheral cannabinoid system
      in the crotalphine effect and its interaction with the opioid system.
      EXPERIMENTAL APPROACH: Hyperalgesia was evaluated using the rat paw pressure
      test. Involvement of the cannabinoid system was determined using a selective
      cannabinoid receptor antagonist. Cannabinoid and opioid receptor activation were
      evaluated in paw slices by immunofluorescence assays using conformation state
      sensitive antibodies. The release of endogenous opioid peptides from skin tissue
      was measured using a commercial enzyme immunoassay (EIA). KEY RESULTS: Both p.o.
      (0.008-1.0 MUg.kg(-1) ) and intraplantar (0.0006 MUg per paw) administration of
      crotalphine induced antinociception in PGE2 -induced hyperalgesia.
      Antinociception by p.o. crotalphine (1 MUg.kg(-1) ) was blocked by AM630 (50 MUg
      per paw), a CB2 receptor antagonist, and by antiserum anti-dynorphin A (1 MUg per
      paw). Immunoassay studies confirmed that crotalphine increased the activation of
      both kappa-opioid (51.7%) and CB2 (28.5%) receptors in paw tissue. The local
      release of dynorphin A from paw skin was confirmed by in vitro EIA and blocked by
      AM630. CONCLUSIONS AND IMPLICATIONS: Crotalphine-induced antinociception involves
      peripheral CB2 cannabinoid receptors and local release of dynorphin A, which is
      dependent on CB2 receptor activation. These results enhance our understanding of
      the mechanisms involved in the peripheral effect of crotalphine, as well as the
      interaction between the opioid and cannabinoid systems.

PMID- 24460676
TI  - Calcium influx pathways in breast cancer: opportunities for pharmacological
      intervention.
AB  - Ca(2+) influx through Ca(2+) permeable ion channels is a key trigger and
      regulator of a diverse set of cellular events, such as neurotransmitter release
      and muscle contraction. Ca(2+) influx is also a regulator of processes relevant
      to cancer, including cellular proliferation and migration. This review focuses on
      calcium influx in breast cancer cells as well as the potential for
      pharmacological modulators of specific Ca(2+) influx channels to represent future
      agents for breast cancer therapy. Altered expression of specific calcium
      permeable ion channels is present in some breast cancers. In some cases, such
      changes can be related to breast cancer subtype and even prognosis. In vitro and
      in vivo models have now helped identify specific Ca(2+) channels that play
      important roles in the proliferation and invasiveness of breast cancer cells.
      However, some aspects of our understanding of Ca(2+) influx in breast cancer
      still require further study. These include identifying the mechanisms responsible
      for altered expression and the most effective therapeutic strategy to target
      breast cancer cells through specific Ca(2+) channels. The role of Ca(2+) influx
      in processes beyond breast cancer cell proliferation and migration should become
      the focus of studies in the next decade. 

PMID- 24460679
TI  - Not the right time: why parents refuse to let their daughters have the human
      papillomavirus vaccination.
AB  - AIM: To explore why parents refused to allow their 10- to 12-year-old daughters
      to receive the human papillomavirus (HPV) vaccination from the Swedish school
      based vaccination programme. METHODS: Individual interviews with 25 parents who
      had been offered, but not consented to, their daughters receiving the HPV
      vaccination. RESULTS: Five themes emerged through the interviews: 1) she is just
      a little girl, 2) inadequate information, 3) not compatible with our way of life,
      4) scepticism about the vaccination and 5) who can you trust? The parents made
      their decisions with their child's best interests in mind. This was not
      considered the right time, and the vaccine was perceived as unnecessary and
      different from other vaccines. Mistrust in Government recommendations and a lack
      of evidence or information were other reasons to decline. CONCLUSION: The
      decision-making process was complex. These parents preferred to wait until their
      daughter was older and believed the information they received from the school
      health system was insufficient. The results indicate that a more flexible HPV
      vaccination schedule may improve vaccine uptake. This includes more transparent
      information about the virus and the vaccine and information about who to contact
      to get the daughter vaccinated at a later date.

PMID- 24460680
TI  - Complete and long-lasting cytologic and molecular remission of FIP1L1-PDGFRA
      positive acute eosinophil myeloid leukaemia, treated with low-dose imatinib
      monotherapy.
AB  - Myeloproliferative neoplasms associated with FIP1L1-PDGFR rearrangements
      represent a rare subset of myeloid and lymphoid malignancies, characterised by
      the presence of eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 genes.
      The fusion product of such genes is a tyrosine kinase oncoprotein sensitive to
      imatinib, which to date results to be the standard of care for FIP1L1-PDGFRA
      positive chronic myeloproliferative disorders with eosinophilia. However, the
      coexistence of FIP1L1-PDGFRA rearrangement associated with acute myeloid
      leukaemia is extremely rare. Here, we report a rare case of FIP1L1-PDGFRA
      positive acute myeloid leukaemia, with marked peripheral blood and bone marrow
      eosinophilia, treated with low dose of imatinib monotherapy, achieving a rapid
      and long-lasting complete cytologic and molecular remission, without need for
      intensive chemotherapy. 

PMID- 24460681
TI  - Linking phenological shifts to species interactions through size-mediated
      priority effects.
AB  - Interannual variation in seasonal weather patterns causes shifts in the relative
      timing of phenological events of species within communities, but we currently
      lack a mechanistic understanding of how these phenological shifts affect species
      interactions. Identifying these mechanisms is critical to predicting how
      interannual variation affects populations and communities. Species' phenologies,
      particularly the timing of offspring arrival, play an important role in the
      annual cycles of community assembly. We hypothesize that shifts in relative
      arrival of offspring can alter interspecific interactions through a mechanism
      called size-mediated priority effects (SMPE), in which individuals that arrive
      earlier can grow to achieve a body size advantage over those that arrive later.
      In this study, we used an experimental approach to isolate and quantify the
      importance of SMPE for species interactions. Specifically, we simulated shifts in
      relative arrival of the nymphs of two dragonfly species to determine the
      consequences for their interactions as intraguild predators. We found that shifts
      in relative arrival altered not only predation strength but also the nature of
      predator-prey interactions. When arrival differences were great, SMPE allowed the
      early arriver to prey intensely upon the late arriver, causing exclusion of the
      late arriver from nearly all habitats. As arrival differences decreased, the
      early arriver's size advantage also decreased. When arrival differences were
      smallest, there was mutual predation, and the two species coexisted in similar
      abundances across habitats. Importantly, we also found a nonlinear scaling
      relationship between shifts in relative arrival and predation strength.
      Specifically, small shifts in relative arrival caused large changes in predation
      strength while subsequent changes had relatively minor effects. These results
      demonstrate that SMPE can alter not only the outcome of interactions but also the
      demographic rates of species and the structure of communities. Elucidating the
      mechanisms that link phenological shifts to species interactions is crucial for
      understanding the dynamics of seasonal communities as well as for predicting the
      effects of climate change on these communities.

PMID- 24460682
TI  - Blended learning in situated contexts: 3-year evaluation of an online peer review
      project.
AB  - BACKGROUND: Situated and sociocultural perspectives on learning indicate that the
      design of complex tasks supported by educational technologies holds potential for
      dental education in moving novices towards closer approximation of the clinical
      outcomes of their expert mentors. A cross-faculty-, student-centred, web-based
      project in operative dentistry was established within the Universitas 21 (U21)
      network of higher education institutions to support university goals for
      internationalisation in clinical learning by enabling distributed interactions
      across sites and institutions. This paper aims to present evaluation of one
      dental faculty's project experience of curriculum redesign for deeper student
      learning. METHODS: A mixed-method case study approach was utilised. Three cohorts
      of second-year students from a 5-year bachelor of dental surgery (BDS) programme
      were invited to participate in annual surveys and focus group interviews on
      project completion. Survey data were analysed for differences between years using
      multivariate logistical regression analysis. Thematic analysis of questionnaire
      open responses and interview transcripts was conducted. RESULTS: Multivariate
      logistic regression analysis noted significant differences across items over time
      indicating learning improvements, attainment of university aims and the positive
      influence of redesign. Students perceived the enquiry-based project as
      stimulating and motivating, and building confidence in operative techniques.
      Institutional goals for greater understanding of others and lifelong learning
      showed improvement over time. Despite positive scores, students indicated global
      citizenship and intercultural understanding were conceptually challenging.
      CONCLUSIONS: Establishment of online student learning communities through a
      blended approach to learning stimulated motivation and intellectual engagement,
      thereby supporting a situated approach to cognition. Sociocultural perspectives
      indicate that novice-expert interactions supported student development of
      professional identities.

PMID- 24460683
TI  - Incorporating the type and direction information in predicting novel regulatory
      interactions between HIV-1 and human proteins using a biclustering approach.
AB  - BACKGROUND: Discovering novel interactions between HIV-1 and human proteins would
      greatly contribute to different areas of HIV research. Identification of such
      interactions leads to a greater insight into drug target prediction. Some recent
      studies have been conducted for computational prediction of new interactions
      based on the experimentally validated information stored in a HIV-1-human protein
      protein interaction database. However, these techniques do not predict any
      regulatory mechanism between HIV-1 and human proteins by considering interaction
      types and direction of regulation of interactions. RESULTS: Here we present an
      association rule mining technique based on biclustering for discovering a set of
      rules among human and HIV-1 proteins using the publicly available HIV-1-human PPI
      database. These rules are subsequently utilized to predict some novel
      interactions among HIV-1 and human proteins. For prediction purpose both the
      interaction types and direction of regulation of interactions, (i.e., virus-to
      host or host-to-virus) are considered here to provide important additional
      information about the regulation pattern of interactions. We have also studied
      the biclusters and analyzed the significant GO terms and KEGG pathways in which
      the human proteins of the biclusters participate. Moreover the predicted rules
      have also been analyzed to discover regulatory relationship between some human
      proteins in course of HIV-1 infection. Some experimental evidences of our
      predicted interactions have been found by searching the recent literatures in
      PUBMED. We have also highlighted some human proteins that are likely to act
      against the HIV-1 attack. CONCLUSIONS: We pose the problem of identifying new
      regulatory interactions between HIV-1 and human proteins based on the existing
      PPI database as an association rule mining problem based on biclustering
      algorithm. We discover some novel regulatory interactions between HIV-1 and human
      proteins. Significant number of predicted interactions has been found to be
      supported by recent literature.

PMID- 24460685
TI  - Impact of dental caries and trauma on quality of life among 5- to 6-year-old
      children: perceptions of parents and children.
AB  - OBJECTIVE: To assess the impact of dental caries and traumatic dental injuries
      (TDI) on the oral health-related quality of life (OHRQoL) of 5- to 6-year-olds
      according to both self- and parental reports. METHODS: A total of 335 pairs of
      parents and children who sought dental screening at the Dental School, University
      of Sao Paulo, completed the Scale of Oral Health Outcomes for 5-year-old children
      (SOHO-5), which consists of a child self-report and a parental proxy-report
      version. Three calibrated examiners assessed the experience of caries according
      to primary teeth that were decayed, indicated for extraction due to caries, or
      filled (def-t). TDI were classified into uncomplicated and complicated injuries.
      Poisson regression models were used to associate the different clinical and
      sociodemographic factors to the outcome. RESULTS: Overall, 74.6% of children
      reported an oral impact, and the corresponding estimate for parental reports was
      70.5%. The mean (standard deviation) SOHO-5 scores in child self-report and
      parental versions were 3.32(3.22) and 5.18(6.28), respectively. In both versions,
      caries was associated with worse children's OHRQoL, for the total score and all
      SOHO-5 items (P < 0.001). In contrast, TDI did not have a negative impact on
      children's OHRQoL, with the exception of two items of the parental version and
      one item of the child self-report version. In the final multivariate adjusted
      models, there was a gradient in the association between caries experience and
      child's OHRQoL with worse SOHO-5 score at each consecutive level with more severe
      caries experience, for both child and parental perceptions [RR (CI 95%) = 6.37
      (4.71, 8.62) and 10.81 (7.65, 15.27)], respectively. A greater family income had
      a positive impact on the children's OHRQoL for child and parental versions [RR
      (CI 95%) = 0.68 (0.49, 0.94) and 0.70 (0.54, 0.90)], respectively. CONCLUSIONS:
      Dental caries, but not TDI, is associated with worse OHRQoL of 5- to 6-year-old
      children in terms of perceptions of both children and their parents. Families
      with higher income report better OHRQoL at this age, independent of the presence
      of oral diseases.

PMID- 24460684
TI  - Polycomb group gene BMI1 controls invasion of medulloblastoma cells and inhibits
      BMP-regulated cell adhesion.
AB  - BACKGROUND: Medulloblastoma is the most common intracranial childhood malignancy
      and a genetically heterogeneous disease. Despite recent advances, current
      therapeutic approaches are still associated with high morbidity and mortality.
      Recent molecular profiling has suggested the stratification of medulloblastoma
      from one single disease into four distinct subgroups namely: WNT Group (best
      prognosis), SHH Group (intermediate prognosis), Group 3 (worst prognosis) and
      Group 4 (intermediate prognosis). BMI1 is a Polycomb group repressor complex gene
      overexpressed across medulloblastoma subgroups but most significantly in Group 4
      tumours. Bone morphogenetic proteins are morphogens belonging to TGF-beta
      superfamily of growth factors, known to inhibit medulloblastoma cell
      proliferation and induce apoptosis. RESULTS: Here we demonstrate that human
      medulloblastoma of Group 4 characterised by the greatest overexpression of BMI1,
      also display deregulation of cell adhesion molecules. We show that BMI1 controls
      intraparenchymal invasion in a novel xenograft model of human MB of Group 4,
      while in vitro assays highlight that cell adhesion and motility are controlled by
      BMI1 in a BMP dependent manner. CONCLUSIONS: BMI1 controls MB cell migration and
      invasion through repression of the BMP pathway, raising the possibility that BMI1
      could be used as a biomarker to identify groups of patients who may benefit from
      a treatment with BMP agonists.

PMID- 24460686
TI  - Correlations among various ocular parameters in clinically unilateral
      pseudoexfoliation syndrome.

PMID- 24460687
TI  - Retama monosperma n-hexane extract induces cell cycle arrest and extrinsic
      pathway-dependent apoptosis in Jurkat cells.
AB  - BACKGROUND: Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.),
      locally named as "R'tam", is an annual and spontaneous plant belonging to the
      Fabaceae family. In Morocco, Retama genus is located in desert regions and across
      the Middle Atlas and it has been widely used in traditional medicine in many
      countries. In this study, we show that Retama monosperma hexane extract presents
      significant anti-leukemic effects against human Jurkat cells. METHODS: Human
      Jurkat cells, together with other cell lines were screened with different
      concentrations of Retama monosperma hexane extract at different time intervals.
      Growth inhibition was determined using luminescent-based viability assays. Cell
      cycle arrest and apoptosis were measured by flow cytometry analysis. Combined
      caspase 3 and 7 activities were measured using luminometric caspase assays and
      immunoblots were performed to analyze expression of relevant pro- and anti
      apoptotic proteins. GC-MS were used to determine the chemical constituents of the
      active extract. RESULTS: Retama monosperma hexane extract (Rm-HE) showed
      significant cytotoxicity against Jurkat cells, whereas it proved to be
      essentially ineffective against both normal mouse fibroblasts (NIH3T3) and normal
      lymphocytes (TK-6). Cytometric analysis indicated that Rm-HE promoted cell cycle
      arrest and apoptosis induction accompanied by DNA damage induction indicated by
      an increase in p-H2A.X levels. Rm-HE induced apoptosis was partially JNK
      dependent and characterized by an increase in Fas-L levels together with
      activation of caspases 8, 3, 7 and 9, whereas neither the pro-apoptotic nor anti
      apoptotic mitochondrial membrane proteins analyzed were significantly altered.
      Chemical identification analysis indicated that alpha-linolenic acid,
      campesterol, stigmasterol and sitosterol were the major bioactive components
      within the extract. CONCLUSIONS: Our data suggest that bioactive compounds
      present in Rm-HE show significant anti leukemic activity inducing cell cycle
      arrest and cell death that operates, at least partially, through the extrinsic
      apoptosis pathway.

PMID- 24460688
TI  - Infiltration and sealing versus fluoride treatment of occlusal caries lesions in
      primary molar teeth. 2-3 years results.
AB  - BACKGROUND: Studies examining the efficacy of sealing occlusal caries lesions in
      the primary dentition are limited, and no studies have so far examined the
      efficacy of infiltrating occlusal lesions on primary molar teeth. OBJECTIVES:
      This study aimed to evaluate the efficacy of infiltrating, sealing, or fluoride
      varnishing on the occlusal surfaces with initial caries lesions. DESIGN: Split
      mouth design study was carried out with 50 children aged between 5 and 8 years
      with three occlusal lesions. After randomization, one lesion was infiltrated with
      ICON and varnished with Duraphat (I+F), one lesion was sealed with Delton and
      varnished with Duraphat (S+F), and one lesion only varnished with Duraphat (F).
      RESULTS: Lesion status could be followed on radiographs on 47 children after 2-3
      years (mean=22 months). Seven lesions in the I+F group, 9 lesions in the S+F, and
      17 lesions in the F group showed radiographic progression. A significant
      difference in lesion progression was only found between the I+F- and the F group
      of teeth (P = 0.021). CONCLUSIONS: Infiltration and sealing occlusal surfaces
      with initial caries lesions on primary molar teeth showed a high efficacy in
      arresting caries progression, significant for the I+F or borderline significant
      for the S+F compared with the F group.

PMID- 24460689
TI  - Tactics for teaching evidenced-based practice: determining the level of evidence
      of a study.

PMID- 24460690
TI  - Explaining ecological clusters of maternal depression in South Western Sydney.
AB  - BACKGROUND: The aim of the qualitative study reported here was to: 1) explain the
      observed clustering of postnatal depressive symptoms in South Western Sydney; and
      2) identify group-level mechanisms that would add to our understanding of the
      social determinants of maternal depression. METHODS: Critical realism provided
      the methodological underpinning for the study. The setting was four local
      government areas in South Western Sydney, Australia. Child and Family
      practitioners and mothers in naturally occurring mothers groups were interviewed.
      RESULTS: Using an open coding approach to maximise emergence of patterns and
      relationships we have identified seven theoretical concepts that might explain
      the observed spatial clustering of maternal depression. The theoretical concepts
      identified were: Community-level social networks; Social Capital and Social
      Cohesion; "Depressed community"; Access to services at the group level; Ethnic
      segregation and diversity; Supportive social policy; and Big business.
      CONCLUSIONS: We postulate that these regional structural, economic, social and
      cultural mechanisms partially explain the pattern of maternal depression observed
      in families and communities within South Western Sydney. We further observe that
      powerful global economic and political forces are having an impact on the local
      situation. The challenge for policy and practice is to support mothers and their
      families within this adverse regional and global-economic context.

PMID- 24460692
TI  - Oxygen removal during pathogen inactivation with riboflavin and UV light
      preserves protein function in plasma for transfusion.
AB  - BACKGROUND AND OBJECTIVE: Photochemical pathogen inactivation technologies (PCT)
      for individual transfusion products act by inhibition of replication through
      irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on
      the blood component's integrity has caused reluctance to introduce this
      technology in routine practice. This work aims to uncover the mechanism of damage
      to plasma constituents by riboflavin pathogen reduction technology (RF-PRT).
      METHODS: Activity and antigen of plasma components were determined following RF
      PRT in the presence or absence of dissolved molecular oxygen. RESULTS: Employing
      ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and
      antigen are reduced by 23 +/- 8% and 29 +/- 9% (n = 24), respectively, which
      corroborates with a mean decrease of 25% observed for other coagulation factors.
      Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious
      indication of additional proteolysis nor is riboflavin able to directly inhibit
      the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT
      protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a
      direct role for reactive oxygen species. Redox dye measurements indicate that
      superoxide anions are specifically generated during RF-PRT. Protein carbonyl
      content as a marker of disseminated irreversible biomolecular damage was
      significantly increased (3.1 +/- 0.8 vs. 1.6 +/- 0.5 nmol/mg protein) following
      RF-PRT, but not in the absence of dissolved molecular oxygen (1.8 +/- 0.4
      nmol/mg). CONCLUSIONS: RF-PRT of single plasma units generates reactive oxygen
      species that adversely affect biomolecular integrity of relevant plasma
      constituents, a side-effect, which can be bypassed by applying hypoxic conditions
      during the pathogen inactivation process.

PMID- 24460691
TI  - Positive allosteric modulators of the MU-opioid receptor: a novel approach for
      future pain medications.
AB  - Morphine and other agonists of the MU-opioid receptor are used clinically for
      acute and chronic pain relief and are considered to be the gold standard for pain
      medication. However, these opioids also have significant side effects, which are
      also mediated via activation of the MU-opioid receptor. Since the latter half of
      the twentieth century, researchers have sought to tease apart the mechanisms
      underlying analgesia, tolerance and dependence, with the hope of designing drugs
      with fewer side effects. These efforts have revolved around the design of
      orthosteric agonists with differing pharmacokinetic properties and/or selectivity
      profiles for the different opioid receptor types. Recently, MU-opioid receptor
      positive allosteric modulators (MU-PAMs) were identified, which bind to a
      (allosteric) site on the MU-opioid receptor separate from the orthosteric site
      that binds an endogenous agonist. These allosteric modulators have little or no
      detectable functional activity when bound to the receptor in the absence of
      orthosteric agonist, but can potentiate the activity of bound orthosteric
      agonist, seen as an increase in apparent potency and/or efficacy of the
      orthosteric agonist. In this review, we describe the potential advantages that a
      MU-PAM approach might bring to the design of novel therapeutics for pain that may
      lack the side effects currently associated with opioid therapy. LINKED ARTICLES:
      This article is part of a themed section on Opioids: New Pathways to Functional
      Selectivity. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24460693
TI  - Kawasaki Disease has so much to teach us!
AB  - Kawasaki Disease (KD) is primarily a childhood vasculitis of mid-size muscular
      arteries, of which the coronary arteries (CA) are most clinically significant.
      Although timely treatment with pooled intravenous immunoglobulin (IVIG) has
      significantly reduced CA pathology, as determined by ECHO cardiology, about 30%
      of children still develop potentially fatal aneurysms, thrombi, or stenosis. This
      paper describes several additional pathologies and phenomena of undetermined
      significance, e.g. myocarditis, endocarditis with fibroelastosis, adrenal
      medullary necrosis, arterial smooth muscle cell transition into proliferating
      myofibroblasts, pneumonia in patients dying from KD, and calcification of
      organizing thrombi.

PMID- 24460694
TI  - Prognostic value of 1p deletion for multiple myeloma: a meta-analysis.
AB  - INTRODUCTION: Previous studies have indicated that a deletion on the short arm of
      chromosome 1 negatively predicts survival in patients with multiple myeloma (MM).
      Due to the small sample size in each study, we performed this meta-analysis to
      comprehensively investigate the association between the 1p deletion and survival
      in patients with MM. METHODS: A literature search was conducted in both foreign
      and Chinese databases, including SinoMed, CNKI, Wanfang, PubMed, EMBASE, and
      Scopus. Hazard ratios (HR) with 95% confidence intervals (CI) for overall
      survival (OS) and progression-free survival (PFS) in 11 eligible articles were
      extracted or calculated to analyze the pooled HR, which was estimated by fixed
      effect or random-effect models based on the heterogeneity between included
      articles. A subgroup analysis and a meta-regression were conducted, and Galbraith
      plots were generated to examine any possible heterogeneity. RESULTS: The HRs for
      OS were available in nine articles, whereas five articles discussed HRs for PFS.
      The HR with 95%CI was 1.989 (95%CI 1.522-2.600, P = 0.017, I(2)  = 57.1%) when
      comparing the OS of patients with 1p deletion with the OS of those without this
      deletion. For PFS, 1p deletion still predicted a poor prognosis (HR 2.11, 95%CI
      1.54-2.88, P = 0.292, I(2)  = 19.3%). Moreover, the subgroup analysis suggested
      that either the deleted gene on 1p or techniques for detecting chromosome
      abnormalities contributed to the heterogeneity, which was partially consistent
      with the results derived from a meta-regression analysis and the Galbraith plot
      method. CONCLUSION: Our meta-analysis provides globally quantifiable confirmation
      of the adverse prognostic role of 1p deletion in OS and PFS for patients with MM.

PMID- 24460695
TI  - Using single cell sequencing data to model the evolutionary history of a tumor.
AB  - BACKGROUND: The introduction of next-generation sequencing (NGS) technology has
      made it possible to detect genomic alterations within tumor cells on a large
      scale. However, most applications of NGS show the genetic content of mixtures of
      cells. Recently developed single cell sequencing technology can identify
      variation within a single cell. Characterization of multiple samples from a tumor
      using single cell sequencing can potentially provide information on the
      evolutionary history of that tumor. This may facilitate understanding how key
      mutations accumulate and evolve in lineages to form a heterogeneous tumor.
      RESULTS: We provide a computational method to infer an evolutionary mutation tree
      based on single cell sequencing data. Our approach differs from traditional
      phylogenetic tree approaches in that our mutation tree directly describes
      temporal order relationships among mutation sites. Our method also accommodates
      sequencing errors. Furthermore, we provide a method for estimating the proportion
      of time from the earliest mutation event of the sample to the most recent common
      ancestor of the sample of cells. Finally, we discuss current limitations on
      modeling with single cell sequencing data and possible improvements under those
      limitations. CONCLUSIONS: Inferring the temporal ordering of mutational sites
      using current single cell sequencing data is a challenge. Our proposed method may
      help elucidate relationships among key mutations and their role in tumor
      progression.

PMID- 24460697
TI  - Population-based study shows improved postnatal growth in preterm very-low
      birthweight infants between 1995 and 2010.
AB  - AIM: To assess whether the postnatal growth of preterm very-low-birthweight
      (VLBW) infants, as determined by measures of postnatal growth failure (PNGF),
      improved during the period 1995-2010 and to evaluate postnatal growth by
      gestational age (GA) and intrauterine growth groups. METHODS: The study was based
      on the Israel national VLBW infant database and comprised 13 531 VLBW infants of
      24-32 weeks' GA, discharged at a postmenstrual age of <=40 weeks. Z-scores were
      determined for weight at birth and discharge. Severe and mild PNGF was defined as
      a decrease >2 and 1-2 z-scores, respectively. Three time periods were considered:
      1995-2000, 2001-2005 and 2006-2010. Multinomial logistic regression was used to
      assess the independent effect of time period on PNGF. RESULTS: Severe PNGF
      decreased from 11.7% in 1995-2000 to 7.2% in 2001-2005 and 5.2% in 2006-2010.
      Infants born in 2006-2010 had sixfold lower odds for severe PNGF than babies born
      in 1995-2000 (adjusted odds ratio 0.17, 95% confidence interval 0.14-0.21) and
      <twofold lower odds for mild PNGF (adjusted odds ratio 0.42, 95% confidence
      interval 0.39-0.48). CONCLUSION: We demonstrated a marked decline in PNGF among
      preterm VLBW infants from 1995-2000 to 2006-2010. This decline was even present
      in extremely premature infants.

PMID- 24460696
TI  - Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium
      phosphate induces osteon formation.
AB  - Vascularization of an artificial graft represents one of the most significant
      challenges facing the field of bone tissue engineering. Over the past decade,
      strategies to vascularize artificial scaffolds have been intensively evaluated
      using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In
      this work, we observed that CaP-based biomaterials implanted into rat calvarial
      defects showed remarkably accelerated formation and mineralization of new woven
      bone in defects in the initial stages, at a rate of ~60 MUm/day (0.8 mg/day),
      which was considerably higher than normal bone growth rates (several MUm/day, 0.1
      mg/day) in implant-free controls of the same age. Surprisingly, we also observed
      histological evidence of primary osteon formation, indicated by blood vessels in
      early-region fibrous tissue, which was encapsulated by lamellar osteocyte
      structures. These were later fully replaced by compact bone, indicating complete
      regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only
      osteoinductive, but vasculogenic, and it may have contributed to the bone
      regeneration, despite an absence of osteons in normal rat calvaria. Further
      investigation will involve how this strategy can regulate formation of
      vascularized cortical bone such as by control of degradation rate, and use of
      models of long, dense bones, to more closely approximate repair of human cortical
      bone. 

PMID- 24460698
TI  - Letter from the editor.

PMID- 24460700
TI  - The effectiveness of faecal removal methods of pasture management to control the
      cyathostomin burden of donkeys.
AB  - BACKGROUND: The level of anthelmintic resistance within some cyathostomin
      parasite populations has increased to the level where sole reliance on
      anthelmintic-based control protocols is not possible. Management-based nematode
      control methods, including removal of faeces from pasture, are widely recommended
      for use in association with a reduction in anthelmintic use to reduce selection
      pressure for drug resistance; however, very little work has been performed to
      quantitatively assess the effectiveness of such methods. METHODS: We analysed
      data obtained from 345 donkeys at The Donkey Sanctuary (Devon, UK), managed under
      three different pasture management techniques, to investigate the effectiveness
      of faeces removal in strongyle control in equids. The management groups were as
      follows: no removal of faeces from pasture, manual, twice-weekly removal of
      faeces from pasture and automatic, twice-weekly removal of faeces from pasture
      (using a mechanical pasture sweeper). From turn-out onto pasture in May, monthly
      faecal egg counts were obtained for each donkey and the dataset subjected to an
      auto regressive moving average model. RESULTS: There was little to no difference
      in faecal egg counts between the two methods of faecal removal; both resulted in
      significantly improved cyathostomin control compared to the results obtained from
      the donkeys that grazed pasture from which there was no faecal removal.
      CONCLUSIONS: This study represents a valuable and unique assessment of the
      effectiveness of the removal of equine faeces from pasture, and provides an
      evidence base from which to advocate twice-weekly removal of faeces from pasture
      as an adjunct for equid nematode control. Widespread adoption of this practice
      could substantially reduce anthelmintic usage, and hence reduce selection
      pressure for nematode resistance to the currently effective anthelmintic
      products.

PMID- 24460699
TI  - Genetics and morphology characterize the dinoflagellate Symbiodinium voratum, n.
      sp., (Dinophyceae) as the sole representative of Symbiodinium Clade E.
AB  - Dinoflagellates in the genus Symbiodinium are ubiquitous in shallow marine
      habitats where they commonly exist in symbiosis with cnidarians. Attempts to
      culture them often retrieve isolates that may not be symbiotic, but instead exist
      as free-living species. In particular, cultures of Symbiodinium clade E obtained
      from temperate environments were recently shown to feed phagotrophically on
      bacteria and microalgae. Genetic, behavioral, and morphological evidence indicate
      that strains of clade E obtained from the northwestern, southwestern, and
      northeastern temperate Pacific Ocean as well as the Mediterranean Sea constitute
      a single species: Symbiodinium voratum n. sp. Chloroplast ribosomal 23S and
      mitochondrial cytochrome b nucleotide sequences were the same for all isolates.
      The D1/D2 domains of nuclear ribosomal DNA were identical among Western Pacific
      strains, but single nucleotide substitutions differentiated isolates from
      California (USA) and Spain. Phylogenetic analyses demonstrated that S. voratum is
      well-separated evolutionarily from other Symbiodinium spp. The motile, or
      mastigote, cells from different cultures were morphologically similar when
      observed using light, scanning, and transmission electron microscopy; and the
      first complete Kofoidian plate formula for a Symbiodinium sp. was characterized.
      As the largest of known Symbiodinium spp., the average coccoid cell diameters
      measured among cultured isolates ranged between 12.2 (+/- 0.2 SE) and 13.3 (+/-
      0.2 SE) MUm. Unique among species in the genus, a high proportion (approximately
      10-20%) of cells remain motile in culture during the dark cycle. Although S.
      voratum occurs on surfaces of various substrates and is potentially common in the
      plankton of coastal areas, it may be incapable of forming stable mutualistic
      symbioses.

PMID- 24460701
TI  - Treatments to slow progression of autosomal dominant polycystic kidney disease:
      systematic review and meta-analysis of randomized trials.
AB  - AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic
      disorder that leads to kidney failure. Our aim was to undertake a meta-analysis
      of randomized trials of interventions that have been hypothesized to reduce the
      progression of total kidney volume (TKV) and renal function in ADPKD. METHODS:
      Relevant trials were identified, and outcomes were: change in TKV, total cyst
      volume (TCV), renal function and adverse events. Meta-analysis used random
      effects, with results expressed as mean difference and risk ratio both with 95%
      confidence intervals (CI). RESULTS: Eleven trials (2262 patients) were included.
      Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5
      trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06)
      or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9%
      (95% CI -10.33 to -7.58%) but did not alter eGFR. The vasopressin receptor
      antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI -3.48 to -2.52)
      and slowed kidney function decline over a 3-year period. A single trial (n = 41)
      of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or
      renal dysfunction (P = 0.78). Adverse events were significant for interventions
      in all trials compared with placebo. CONCLUSION: These data suggest that
      somatostatin analogues and vasopressin receptor antagonists attenuate TKV
      increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to
      heterogeneity in study population, drug efficacy and follow-up duration. In the
      future, further well-designed and powered trials of longer duration using new
      biomarkers or therapeutic agents with better tolerance are required.

PMID- 24460702
TI  - Greater migratory propensity in hosts lowers pathogen transmission and impacts.
AB  - Animal migrations are spectacular and migratory species have been shown to
      transmit pathogens that pose risks to human health. Although migration is
      commonly assumed to enhance pathogen dispersal, empirical work indicates that
      migration can often have the opposite effect of lowering disease risk. Key to
      assessing disease threats to migratory species is the ability to predict how
      migratory behaviour influences pathogen invasion success and impacts on migratory
      hosts, thus motivating a mechanistic understanding of migratory host-pathogen
      interactions. Here, we develop a quantitative framework to examine pathogen
      transmission in animals that undergo two-way directed migrations between
      wintering and breeding grounds annually. Using the case of a pathogen transmitted
      during the host's breeding season, we show that a more extreme migratory strategy
      (defined by the time spent away from the breeding site and the total distance
      migrated) lowers the probability of pathogen invasion. Moreover, if migration
      substantially lowers the survival probability of infected animals, then
      populations that spend comparatively less time at the breeding site or that
      migrate longer distances are less vulnerable to pathogen-induced population
      declines. These findings provide theoretical support for two non-exclusive
      mechanisms proposed to explain how seasonal migration can lower infection risk:
      (i) escape from habitats where parasite transmission stages have accumulated and
      (ii) selective removal of infected hosts during strenuous journeys. Our work
      further suggests that barriers to long-distance movement could increase pathogen
      prevalence for vulnerable species, an effect already seen in some animal species
      undergoing anthropogenically induced migratory shifts. 

PMID- 24460704
TI  - Perceptions of symptoms and expectations of advanced therapy for Parkinson's
      disease: preliminary report of a Patient-Reported Outcome tool for Advanced
      Parkinson's disease (PRO-APD).
AB  - BACKGROUND: What do patients expect from a treatment? A patient-centred approach
      to treatment is becoming necessary given the choices for invasive treatments for
      Parkinson's disease. Patient's perceptions of severity and expectations from
      complex therapies have not been studied. We describe the rationale and concept of
      developing a Patient-Reported Outcome (PRO) tool to assess perceptions of symptom
      severity and expectations of therapy. We report preliminary findings from use of
      the tool, association with clinical factors, and illustrate the potential use in
      individual patients awaiting therapy. METHODS: Patient symptoms were grouped into
      four domains, with 8 motor, 7 non-motor, 7 psychological and 4 social questions.
      For each question, symptom severity was rated on a Likert scale scoring from 0
      (no problem) to 7 (perceived as a severe problem). Similarly, the expectation for
      each symptom to change after therapy was rated on a Likert scale: score -3
      (expected to be very much worse) to + 3 (expected to be very much improved).
      RESULTS: 22 consecutive patients, routinely planned to receive one of Deep Brain
      Stimulation/Intrajejunal Levodopa Infusion/Apomorphine Infusion therapies, were
      recruited: 13 male, mean (+/-sd) age: 65.6 (+/-9.5) years, mean (+/-sd) disease
      duration: 14.3 (+/-5.7) years. Subjective severity scores are reported as mean
      (+/-sd) / maximum possible score: (i) motor 23.5 (+/-7.5) / 56, (ii) non-motor
      15.5 (+/-5.6) / 49, (iii) cognitive - psychological 12.4 (+/-5.8) / 49, (iv)
      social 9.3 (+/-4.1) / 28. Expectation of change (improvement) scores are reported
      as mean (+/-sd) / maximum possible score of: (i) motor 14.0 (+/-5.6) / 24, (ii)
      non-motor 8.5 (+/-4.1) / 21, (iii) cognitive - psychological 7.4 (+/-4.4)/ 21,
      and (iv) social 5.5 (+/-2.8) / 12. For each domain, Spearman correlation
      coefficient showed significant associations between severity and expectation
      within-domain. CONCLUSION: This tool (PRO-APD) provides a description of
      perceived problem severity and expectation of treatments encompassing a holistic
      patient-driven view of care. PD patients about to receive complex therapy have
      moderately high perception of symptom load in multiple domains, and expect
      substantial improvements in multiple domains. These preliminary findings may be
      useful in documenting multi-domain symptoms, as well as counseling patients to
      help them reach realistic expectations and reduce potential dissatisfaction
      following therapy.

PMID- 24460703
TI  - Yeast endocytic adaptor AP-2 binds the stress sensor Mid2 and functions in
      polarized cell responses.
AB  - The AP-2 complex is a heterotetrameric endocytic cargo-binding adaptor that
      facilitates uptake of membrane proteins during mammalian clathrin-mediated
      endocytosis. While budding yeast has clear homologues of all four AP-2 subunits
      which form a complex and localize to endocytic sites in vivo, the function of
      yeast AP-2 has remained enigmatic. Here, we demonstrate that AP-2 is required for
      hyphal growth in Candida albicans and polarized cell responses in Saccharomyces
      cerevisiae. Deletion of APM4, the cargo-binding mu subunit of AP-2, causes
      defects in pseudohyphal growth, generation of a mating projection and the cell
      wall damage response. In an apm4 null mutant, the cell wall stress sensor Mid2 is
      unable to relocalize to the tip of a mating projection following pheromone
      addition, or to the mother bud neck in response to cell wall damage. A direct
      binding interaction between Mid2 and the mu homology domain of Apm4 further
      supports a model in which AP-2 binds Mid2 to facilitate its internalization and
      relocalization in response to specific signals. Thus, Mid2 is the first cargo for
      AP-2 identified in yeast. We propose that endocytic recycling of Mid2 and other
      components is required for polarized cell responses ensuring cell wall deposition
      and is tightly monitored during cell growth. 

PMID- 24460705
TI  - Defective ADAMTS13 synthesis as a possible consequence of NASH in an obese
      patient with recurrent thrombotic thrombocytopenic purpura.
AB  - OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare and devastating
      hematologic disorder frequently associated with multiple organ failure and
      sometimes death. This syndrome is mainly associated with severe deficiency of
      ADAMTS13, a disintegrin and metalloprotease with thrombospondin (TSP)-1 repeats,
      cleaving high molecular weight von Willebrand Factor (ULVWF) multimers. Decreased
      plasma ADAMTS13 activity results in the accumulation of ULVWF multimers with
      consequent platelet activation. Recently, obesity has been considered as a
      potential independent risk factor for TTP, but the reason of this association is
      still unknown. METHODS AND RESULTS: We describe an unusual case of fatal
      recurrent TTP in a morbid obese female with non-alcoholic steatohepatitis (NASH)
      and severe ADAMTS13 activity deficiency due neither to an inhibitory autoantibody
      nor to a gene mutation. CONCLUSIONS: Visceral obesity is associated with non
      alcoholic fatty liver disease (NAFLD) and NASH: we hypothesized that these
      conditions can influence ADAMTS13 antigen and activity. In fact, hepatic stellate
      cells (HSC) are the main producers of ADAMTS13, and a decrease in ADAMTS13
      activity has been reported in liver disease.

PMID- 24460706
TI  - Patient relevant endpoints in oncology: current issues in the context of early
      benefit assessment in Germany.
AB  - The German AMNOG healthcare reform includes a mandatory early-benefit-assessment
      (EBA) at launch. As per German social code, EBA is based on registration trials
      and includes evaluation of the patient-relevant effect of the new medicines
      compared to an appropriate comparator as defined by the Federal Joint Committee
      (G-BA). Current EBA decisions released have unveiled issues regarding the
      acceptance of some patient-relevant endpoints as G-BA and IQWiG are grading the
      endpoints, focusing on overall survival as the preferred endpoint in oncology.A
      taskforce of experienced German outcomes research, medical, health-technology
      assessment and biostatistics researchers in industry was appointed. After
      agreement on core assumptions, a draft position was prepared. Input on iterative
      versions was solicited from a panel of reviewers from industry and external
      stakeholders.Distinctive features of registration trials in oncology need to be
      considered when these studies form basis for EBA, especially in cancer
      indications with long post-progression survival; and with several consecutive
      therapeutic options available post-progression. Ethical committees, caregivers
      and patients often demand cross-over-designs diluting the treatment-effect on
      overall survival. Regulatory authorities require evaluation of morbidity-related
      study endpoints including survival of patients without their disease getting
      worse (i.e., progression-free survival). Also, progression requires treatment
      changes, another strong indicator for its relevance to patients.Based on specific
      guidelines and clinical trial programs that were developed to be consistent with
      regulatory guidance, endpoints in oncology are thoroughly evaluated in terms of
      their patient-relevance. This extensive knowledge and experience should be fully
      acknowledged during EBA when assessing the patient-relevant benefit of innovative
      medicines in oncology. JEL CODES: D61; H51; I18.

PMID- 24460707
TI  - Subgingival microbiota of Sri Lankan tea labourers naive to oral hygiene
      measures.
AB  - AIM: To characterize the subgingival microbiota within a cohort of adult males (n
      = 32) naive to oral hygiene practices, and to compare the composition of
      bacterial taxa present in periodontal sites with various probing depths. MATERIAL
      AND METHODS: Subgingival plaque samples were collected from single shallow pocket
      [pocket probing depth (PPD)<=3 mm] and deep pocket (PPD>=6 mm) sites from each
      subject. A polymerase chain reaction based strategy was used to construct a clone
      library of 16S ribosomal RNA (rRNA) genes for each site. The sequences of ca. 30
      60 plasmid clones were determined for each site to identify resident taxa.
      Microbial composition was compared using a variety of statistical and
      bioinformatics approaches. RESULTS: A total of 1887 cloned 16S rRNA gene
      sequences were analysed, which were assigned to 318 operational taxonomic units
      (98% identity cut-off). The subgingival microbiota was dominated by Firmicutes
      (69.8%), Proteobacteria (16.3%), and Fusobacteria (8.0%). The overall composition
      of microbial communities in shallow sites was significantly different from those
      within deep sites (?-Libshuff, p < 0.001). CONCLUSIONS: A taxonomically diverse
      subgingival microbiota was present within this cohort; however, the structures of
      the microbial communities present in the respective subjects exhibited limited
      variation. Deep and shallow sites contained notably different microbial
      compositions, but this was not correlated with the rate of periodontal
      progression.

PMID- 24460708
TI  - Precursor stage of retinal pigment epithelial tear in age-related macular
      degeneration.

PMID- 24460709
TI  - Cognitive interviews guide design of a new CAM patient expectations
      questionnaire.
AB  - BACKGROUND: No consistent relationship exists between pre-treatment expectations
      and therapeutic benefit from various complementary and alternative medicine (CAM)
      therapies in clinical trials. However, many different expectancy measures have
      been used in those studies, with no validated questionnaires clearly focused on
      CAM and pain. We undertook cognitive interviews as part of a process to develop
      and validate such a questionnaire. METHODS: We reviewed questions about
      expectations of benefits of acupuncture, chiropractic, massage, or yoga for pain.
      Components of the questions - verbs, nouns, response options, terms and phrases
      describing back pain - were identified. Using seven different cognitive interview
      scripts, we conducted 39 interviews to evaluate how individuals with chronic low
      back pain understood these individual components in the context of expectancy
      questions for a therapy they had not yet received. Chosen items were those with
      the greatest agreement and least confusion among participants, and were closest
      to the meanings intended by the investigators. RESULTS: The questionnaire drafted
      for psychometric evaluation had 18 items covering various domains of expectancy.
      "Back pain" was the most consistently interpreted descriptor for this condition.
      The most understandable response options were 0-10 scales, a structure used
      throughout the questionnaire, with 0 always indicating no change, and 10 anchored
      with an absolute descriptor such as "complete relief". The use of words to
      describe midpoints was found to be confusing. The word "expect" held different
      and shifting meanings for participants. Thus paired items comparing "hope" and
      "realistically expect" were chosen to evaluate 5 different aspects of treatment
      expectations (back pain; back dysfunction and global effects; impact of back pain
      on specific areas of life; sleep, mood, and energy; coping). "Impact of back
      pain" on various areas of life was found to be a consistently meaningful concept,
      and more global than "interference". CONCLUSIONS: Cognitive interviews identified
      wordings with considerable agreement among both participants and investigators.
      Some items widely used in clinical studies had different meanings to participants
      than investigators, or were confusing to participants. The final 18-item
      questionnaire is undergoing psychometric evaluation with goals of streamlining as
      well as identifying best items for use when questionnaire length is constrained.

PMID- 24460710
TI  - Speeding the translation of research into evidence-based practice and conducting
      projects that impact healthcare quality, patient outcomes and costs: the "so
      what" outcome factors.

PMID- 24460711
TI  - Novel GPCR paradigms at the MU-opioid receptor.
AB  - Opioids, such as morphine, are the most clinically useful class of analgesic
      drugs for the treatment of acute and chronic pain. However, the use of opioids is
      greatly limited by the development of severe adverse side effects. Consequently,
      drug discovery efforts have been directed towards improving the therapeutic
      profile of opioid-based treatments. Opioid receptors are members of the family of
      GPCRs. As such, the recent GPCR paradigms of biased agonism and allosterism may
      provide novel avenues for more effective analgesics. Biased agonism (or
      functional selectivity) has been described for all the opioid receptor family
      members. Furthermore, the first allosteric modulators of opioid receptors have
      very recently been described. However, identification and quantification of
      biased agonism in a manner that is informative to medicinal chemists and drug
      discovery programmes still remains a challenge. In this review, we examine the
      progress, to date, towards identification and quantification of biased agonism
      and allosterism at the MU-opioid receptor in the context of its implications for
      the discovery of better and safer analgesics. LINKED ARTICLES: This article is
      part of a themed section on Opioids: New Pathways to Functional Selectivity. To
      view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24460712
TI  - Use of IL3 and chromatin-modifying reagents valproic acid and 5-aza-2'
      deoxycytidine to affect mobilized peripheral blood CD34+ cell fate decisions.
AB  - BACKGROUND AND OBJECTIVES: Culture of blood CD34(+) cells with chromatin
      modifying agents can lead to an increase in marrow repopulating cells and in the
      case of valproic acid increased erythroid cell colony formation. We undertook
      research to help understand what effects these reagents have on mobilized
      peripheral blood (MPB) CD34(+) cells. MATERIALS AND METHODS: Mobilized peripheral
      blood was obtained under informed consent and ethics committee approval from nine
      patients and allograft donors. Epigenetic modifiers valproic acid and 5-aza-2'
      deoxycytidine were used singly or in combination with each other and with IL3
      when culturing mobilized peripheral blood CD34(+) cells. Cultured cells were
      subsequently used in flow cytometry and colony-forming unit assay experiments.
      RESULTS: Addition of IL3 to the in vitro cell growth medium improved the
      expansion and maintained the functionality of CD34(+) cells. Valproic acid and
      IL3 also work synergistically to increase the numbers of CD34(+) /CD36(+) double
      positive cells. We found that an apparent increase in red cell colony formation
      was a result of a decrease in white cell colonies, with no overall increase in
      red cell colonies when equivalent numbers of CD34(+) cells are plated.
      CONCLUSIONS: Mobilized peripheral blood CD34(+) stem and progenitor cells are
      affected by chromatin-modifying agents and IL3 giving higher numbers of CD34(+)
      /CD36(+) double-positive erythroid progenitors.

PMID- 24460715
TI  - Cell Proliferation on-line only.

PMID- 24460713
TI  - Synergistic antitumor cytotoxic actions of ascorbate and menadione on human
      prostate (DU145) cancer cells in vitro: nucleus and other injuries preceding cell
      death by autoschizis.
AB  - Scanning (SEM) and transmission electron microscopy (TEM) were used to
      characterize the cytotoxic effects of ascorbate (VC), menadione (VK3), or a
      VC:VK3 combination on a human prostate carcinoma cell line (DU145) following a 1
      h vitamin treatment and a subsequent 24-h incubation in culture medium. Cell
      alterations examined by light and electron microscopy were treatment-dependent
      with VC + VK3 >VK3 > VC > Sham. Oxidative stress-induced damage was found in most
      organelles. This report describes injuries in the tumor cell nucleus (chromatin
      and nucleolus), mitochondria, endomembranes, lysosomal bodies (autophagocytoses)
      and inclusions. Morphologic alterations suggest that cytoskeleton damage is
      likely responsible for the superficial cytoplasmic changes, including major
      changes in cell shape and size and the self-excising phenomena. Unlike apoptotic
      bodies, the excised pieces contain ribonucleoproteins, but not organelles. These
      deleterious events cause a progressive, significant reduction in the tumor cell
      size. During nuclear alterations, the nuclei maintain their envelope during
      chromatolysis and karyolysis until cell death, while nucleoli undergo a
      characteristic segregation of their components. In addition, changes in fat and
      glycogen storage are consistent the cytotoxic and metabolic alterations caused by
      the respective treatments. All cellular ultrastructural changes are consistent
      with cell death by autoschizis and not apoptosis or other kinds of cell death.

PMID- 24460716
TI  - Enhancing ex vivo expansion of cord blood-derived unrestricted somatic stem cells
      for clinical applications.
AB  - OBJECTIVES: To study effects of serum-containing medium (SCM) versus serum-free
      medium (SFM) and influence of seeding density, on rate of expansion of cord blood
      (CB) unrestricted somatic stem cells (USSCs), as a prerequisite for evaluating
      their therapeutic potential in ongoing clinical trials. MATERIAL AND METHODS:
      Isolation, propagation and characterization of USSCs from CB samples were
      performed and followed by their passage 3 culture in SCM and SFM, at cell
      densities of 5, 50, 500 and 5000 cells/cm(2) . RESULTS: The cells were CD44(+) ,
      CD90(+) , CD73(+) , CD105(+) , CD34(-) , CD45(-) , and HLA-DR, with Oct4 & Sox2
      gene expression; they were differentiated into osteoblasts and adipocytes. USSCs
      cultured in SCM had significantly higher population doubling levels (P < 0.01)
      than those cultured in SFM. Those cultured in SCM at 5 cells/cm(2) and those
      cultured in SFM at 50 cells/cm(2) had significantly higher population doubling (P
      < 0.01) levels than those cultured at higher cell densities. CONCLUSIONS: For
      scaling up of USSCs from 106 (?) to 1012 (?) in 6 weeks, culturing of CB-derived
      cells of early passage (<=P3) in SCM at low cell seeding density (5 cells/cm(2) )
      is suggested for increasing cell count with lower passaging frequency, followed
      by culture of expanded USSCs at 50 cells/cm(2) in SFM, to avoid undesirable
      effects of bovine serum in clinical applications.

PMID- 24460717
TI  - Induction of apoptosis and G2 /M cell cycle arrest by Scrophularia striata in a
      human leukaemia cell line.
AB  - OBJECTIVES: Scrophularia striata Boiss (Scrophulariaceae) is a plant that grows
      in northeastern Iran; it has been used traditionally to treat various
      inflammatory disorders. This study was designed to investigate cytotoxic effects
      of S. striata extract, on the Jurkat human leukaemia cell line (T-cell
      leukaemia). MATERIALS AND METHODS: Phytochemical assay by thin layer
      chromatography and 2, 2 diphenyl-1-picryl-hydrazyl were used to evaluate main
      compounds and antioxidant capacity of the plant extract, respectively. Its
      inhibitory effect on Jurkat cells was evaluated by MTT assay. In addition, cell
      cycle distribution and apoptotic cell death were evaluated by propidium iodide
      and annexin V-FITC/ propidium iodide staining. RESULTS: These showed that the
      main components present in S. striata extract included flavonoids, phenolic
      compounds and phenyl propanoids. Treatment with extract was significantly
      cytotoxic to the tumour cell line. In addition, flow cytometry analysis indicated
      that S. striata extract induced cell cycle arrest in G2 /M phase and apoptosis of
      tumour cells. CONCLUSIONS: Results of the study indicated that S. striata extract
      could inhibit leukaemia cell proliferation by inducing G2 /M phase arrest and
      apoptosis.

PMID- 24460718
TI  - Roles of brain and muscle ARNT-like 1 and Wnt antagonist Dkk1 during osteogenesis
      of bone marrow stromal cells.
AB  - OBJECTIVES: Many studies have demonstrated that the clock gene, brain and muscle
      ARNT-like 1 (Bmal1), is directly related to bone ageing by affecting age-related
      changes to mesenchymal stem cells (MSCs). As a main developmental signal, Wnt may
      play an important role in this process. Here, we have aimed to elucidate whether
      Bmal1 positively regulates osteogenesi via Wnt pathways. MATERIALS AND METHODS:
      Bone marrow stromal cells were cultured in basic and in osteo-induction medium
      with Wnt signalling inhibitor Dkk1 and Bmal1 transfection. Proliferation and
      osteogenesis of MSCs, expression of Bmal1 and activation of Wnt signalling were
      investigated by flow cytometry, senescence-associated beta-galactosidase (SA-beta
      gal) staining, real-time quantitative PCR and western blot analysis. RESULTS:
      Expression of Bmal1 (specially after 7 days osteo-induction), activation of Wnt
      signalling and osteo-related factors fell significantly during osteo-induction
      after Dkk1 addition. When cellular Bmal1 was increased by transfection,
      osteogenesis inhibition by Dkk1 was rescued to a certain extent with activation
      of Wnt signalling. However, Dkk1 did not significantly affect proliferation or
      senescence of MSCs during early periods of culture. CONCLUSION: These findings
      demonstrated that Bmal1 and Wnt signalling may have a synergistic effect at a
      particular stage of osteogenesis. Inhibition of Wnt signalling did not greatly
      affect ageing of MSCs through early passages.

PMID- 24460720
TI  - Effects of TiO2 nanotube layers on RAW 264.7 macrophage behaviour and bone
      morphogenetic protein-2 expression.
AB  - OBJECTIVES: To investigate behaviour and osteogenic cytokine expression of
      RAW264.7 macrophages grown on TiO2 nanotube layers. MATERIALS AND METHODS: The
      murine macrophage cell line RAW 264.7 was cultured on TiO2 nanotubes of varying
      diameter; macrophage morphology was examined using scanning electron microscopy.
      Cell adhesion and viability were assessed with the aid of the MTT method and BMP
      2 and TGF-beta gene expression were examined by RT-PCR analysis. Levels of BMP-2,
      TGF-beta1 and ICAM-1 proteins secreted into the supernatant were measured by
      ELISA assay. RESULTS: Macrophages cultured on nanotube layers had spread out
      morphology, the largest (120 nm) nanotube layer eliciting an elongation by 24 h.
      Macrophages adhered significantly less to 120 nm TiO2 nanotubes than to control
      discs at 4 h after application; after 24 h incubation, macrophages were
      sufficiently viable (P < 0.05) on 30 and 70 nm nanotube layers. Increasing
      nanotube diameter led to increased BMP-2 protein secretion and increased BMP-2
      mRNA expression. CONCLUSION: These results demonstrate that nanoscale topography
      of TiO2 nanotube layers can affect macrophage morphology, adhesion, viability and
      BMP-2 expression. Macrophages grown on layers of large nanotubes had the highest
      potential to enhance bone formation during bone healing.

PMID- 24460719
TI  - Role of histone deacetylases in regulation of phenotype of ovine newborn
      pulmonary arterial smooth muscle cells.
AB  - OBJECTIVE: Pulmonary arterial hypertension, characterized by pulmonary vascular
      remodelling and vasoconstriction, is associated with excessive proliferative
      changes in pulmonary vascular walls. However, the role of HDACs in the phenotypic
      alteration of pulmonary arterial smooth muscle cells (PASMC) is largely unknown.
      MATERIAL AND METHODS: Pulmonary arterial smooth muscle cells were isolated from
      newborn sheep. Cell cycle analysis was performed by flow cytometry. mRNA and
      protein expression were measured by real-time PCR and Western blot analysis.
      Wound-healing scratch assay was used to measure cell migration. Contractility of
      newborn PASMCs was determined by gel contraction assay. Chromatin
      immunoprecipitation was used to examine histone modifications along the p21
      promoter region. Global DNA methylation was measured by liquid chromatography
      mass spectroscopy. RESULTS: Inhibition of class I and class II HDACs by apicidin
      and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle
      arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with
      apicidin and HDACi VIII. This was accompanied by increased expression of p21 and
      reduced expression of CCND1 but not p53. HDAC inhibition altered histone codes
      around the p21 promoter region in NPASMC. Apicidin inhibited serum-induced cell
      migration, and modulated profiling of expression of genes encoding pro-oxidant
      and antioxidant enzymes. Contractility and global DNA methylation levels of
      newborn PASMCs were also markedly modulated by apicidin. CONCLUSION: Our results
      demonstrate that class I HDACs are clearly involved in phenotypic alteration of
      newborn PASMC.

PMID- 24460721
TI  - BMP4 promotes vascularization of human adipose stromal cells and endothelial
      cells in vitro and in vivo.
AB  - OBJECTIVES: Vascularization is a major obstacle to clinical application of
      regenerative medicine. Engineered tissues must be able to generate an early
      vascular network that can quickly connect with the host vasculature. Recent
      research demonstrates that natural adipose tissues contain abundant stromal
      cells, which can give rise to pericytes. In this study, we aimed to investigate
      the application of human adipose stromal cells (ASCs) to vascularization, and the
      function of BMP4 protein during vascularization. MATERIALS AND METHODS:
      Immunofluorescence staining for alpha-SMA and PDGFR-beta were utilized to
      identify characteristics of ASCs/pericytes. They were then loaded into a collagen
      fibronectin gel with endothelial cells to assess their vascularization ability,
      both in vitro and in vivo. RESULTS: We showed that the ASCs expressed some of the
      essential markers of pericytes and they were able to promote vascularization with
      endothelial cells in 3D culture, both in vitro and in vivo. BMP4 protein further
      promoted this vascularization. CONCLUSION: Adipose stromal cells promoted
      vascularization by endothelial cells and BMP4 protein further enhanced this
      effect.

PMID- 24460722
TI  - Early intervention in psychosis services: the next generation.

PMID- 24460723
TI  - Using dynamic Brownian bridge movement modelling to measure temporal patterns of
      habitat selection.
AB  - Accurately describing animal space use is vital to understanding how wildlife use
      habitat. Improvements in GPS technology continue to facilitate collection of
      telemetry data at high spatial and temporal resolutions. Application of the
      recently introduced dynamic Brownian bridge movement model (dBBMM) to such data
      is promising as the method explicitly incorporates the behavioural heterogeneity
      of a movement path into the estimated utilization distribution (UD). Utilization
      distributions defining space use are normally estimated for time-scales ranging
      from weeks to months, obscuring much of the fine-scale information available from
      high-volume GPS data sets. By accounting for movement heterogeneity, the dBBMM
      provides a rigorous, behaviourally based estimate of space use between each set
      of relocations. Focusing on UDs generated between individual sets of locations
      allows us to quantify fine-scale circadian variation in habitat use. We used the
      dBBMM to estimate UDs bounding individual time steps for three terrestrial
      species with different life histories to illustrate how the method can be used to
      identify fine-scale variations in habitat use. We also demonstrate how dBBMMs can
      be used to characterize circadian patterns of habitat selection and link fine
      scale patterns of habitat use to behaviour. We observed circadian patterns of
      habitat use that varied seasonally for a white-tailed deer (Odocoileus
      virginianus) and coyote (Canis latrans). We found seasonal patterns in selection
      by the white-tailed deer and were able to link use of conifer forests and
      agricultural fields to behavioural state of the coyote. Additionally, we were
      able to quantify the date in which a Rio Grande wild turkey (Meleagris gallopavo
      intermedia) initiated laying as well as when during the day, she was most likely
      to visit the nest site to deposit eggs. The ability to quantify circadian
      patterns of habitat use may have important implications for research and
      management of wildlife. Additionally, the ability to link such patterns to
      behaviour may aid in the development of mechanistic models of habitat selection. 

PMID- 24460724
TI  - Large cohort study finds a statistically significant association between
      excessive crying in early infancy and subsequent ear symptoms.
AB  - AIM: The diagnosis of infantile colic is based on excessive crying. However,
      several causal factors can account for this disconcerting, nonspecific symptom.
      The main aim of this study was to investigate a possible association between
      excessive crying during the first 6 months of life and subsequent ear problems.
      METHODS: Data from a cohort study of 26 983 Danish children were used. Mothers
      participated in four telephone interviews and one questionnaire and provided
      information on crying in the first 6 months of life and ear symptoms at the ages
      of 6 months, 18 months and 7 years. RESULTS: There was a statistically
      significant association between excessive crying in infancy and subsequent ear
      symptoms. A gradual increase in subsequent ear problems was seen with increasing
      crying time at all the data collection times. CONCLUSIONS: The results of this
      study suggest a possible link between excessive crying and ear infections.
      Whether such a link is causal or due to common underlying factors is still
      unknown. We recommend thorough ear examinations in children with symptoms
      compatible with infantile colic.

PMID- 24460725
TI  - Morphological and molecular characterization of a marine fish trypanosome from
      South Africa, including its development in a leech vector.
AB  - BACKGROUND: Trypanosomes are ubiquitous blood parasites of marine and freshwater
      fishes, typically transmitted by aquatic leeches. Phylogenetic studies have been
      dominated by examples derived from freshwater fishes, with few marine
      representatives. Furthermore, life cycle studies on marine fish trypanosomes have
      focused on those of the northern hemisphere. In this investigation, we have
      examined the life cycle and molecular taxonomy of a marine fish trypanosome from
      South Africa. METHODS: To locate trypanosome stages, leeches were removed from
      fishes captured on the west and south coasts of South Africa, and fish blood
      films and leech squashes were Giemsa-stained and screened; leeches were also
      examined histologically. To determine whether trypanosome stages in fishes and
      leeches were of the same genotype, DNA was extracted from Giemsa-stained fish
      blood films and leech squashes, and from fish whole blood. Fragments of the 18S
      rRNA gene were amplified by PCR using trypanosome-specific primers and sequenced.
      Resulting sequence data were compared with each other and with published
      trypanosome 18S rDNA sequences, and used for phylogenetic analysis. RESULTS:
      Trypanosomes were detected in blood films from fishes of the families Clinidae,
      Blenniidae and Gobiidae. The flagellates ranged in size and staining properties
      within the films and across fish hosts. In squashes and histological sections of
      adult and juvenile leeches, identified as Zeylanicobdella arugamensis,
      trypanosome developmental stages were predominantly slender epimastigotes.
      Sequence data showed that trypanosomes derived from fishes were identical,
      irrespective of whether they were small or large forms; sequences derived largely
      from leech epimastigotes were also identical to those obtained from fish
      trypanosomes. Fish and leech trypanosome sequences fell into a marine fish
      aquatic clade, and aligned most closely with two trypanosome sequences from
      marine fishes off Norway. CONCLUSIONS: Combined morphological and molecular
      methods indicate that the trypanosomes examined here represent a single
      pleomorphic species, rather than the three species described originally. This
      species is identified as Trypanosoma nudigobii Fantham, 1919 with the leech Z.
      arugamensis as its vector, and T. capigobii Fantham, 1919 and T. blenniclini
      Fantham, 1930 are regarded as junior synonyms of the species. Phylogenetic
      analysis establishes its affinity with marine fish trypanosomes off Norway.

PMID- 24460726
TI  - Reduced levels of CCL2 and CXCL10 in systemic lupus erythematosus patients under
      treatment with prednisone, mycophenolate mofetil, or hydroxychloroquine, except
      in a high STAT1 subset.
AB  - INTRODUCTION: Our recent data showed that signal transducers and activators of
      transcription 1 (STAT1), adenosine deaminase acting on RNA (ADAR), C-C motif
      chemokine ligand 2 (CCL2), and C-X-C motif chemokine 10 (CXCL10) were
      significantly elevated in a systemic lupus erythematosus (SLE) cohort compared to
      healthy donors. High and low STAT1 subsets were identified in SLE patient visits.
      The present study analyzed the correlation of common treatments used in SLE with
      the levels of these biomarkers. METHODS: Peripheral blood leukocytes were
      collected from 65 healthy donors and 103 SLE patients, of whom 60 had samples
      from two or more visits. Total RNA was isolated and analyzed for the expression
      of mRNA and microRNA using Taqman real-time polymerase chain reaction (PCR)
      assays. Relative expression of interferon signature genes, CCL2, and CXCL10 were
      determined by the DeltaDeltaCT method. Results were correlated with therapy using
      prednisone, mycophenolate mofetil, and hydroxychloroquine and analyzed by
      Wilcoxon/Kruskal-Wallis test and Fisher's exact test. RESULTS: CCL2 and CXCL10
      were significantly higher in untreated patients compared to treated patients,
      however, in high STAT1 patient visits there is no significant difference between
      treated and untreated patients' visits. When comparing linear regression fits of
      interferon (IFN) score with CCL2 and CXCL10, untreated patients and high STAT1
      patients displayed significantly higher slopes compared to treated patients.
      There was no significant difference between the slopes of high STAT1 and
      untreated patients indicating that CCL2 and CXCL10 were correlated with type-I
      IFN in high STAT1 patients similar to that in untreated patients. CCL2 and CXCL10
      levels in the high STAT1 subset remained high in treated patient visits compared
      to those of the low STAT1 subset. CONCLUSIONS: Among the biomarkers analyzed,
      only CCL2 and CXCL10 showed significantly reduced levels in treated compared to
      untreated SLE patients. STAT1, CCL2, and CXCL10 are potentially useful indicators
      of therapeutic action in SLE patients. Further work is needed to determine
      whether high STAT1 levels convey resistance to therapies commonly used to treat
      SLE and whether STAT1 inhibitors may have therapeutic implication for these
      patients.

PMID- 24460727
TI  - Pregnancy-related low back pain and pelvic girdle pain approximately 14 months
      after pregnancy - pain status, self-rated health and family situation.
AB  - BACKGROUND: Pelvic girdle pain (PGP) in pregnancy is distinct from pregnancy
      related low back pain (PLBP). However, women with combined PLBP and PGP report
      more serious consequences in terms of health and function. PGP has been estimated
      to affect about half of pregnant women, where 25% experience serious pain and 8%
      experience severe disability. To date there are relatively few studies regarding
      persistent PLBP/PGP postpartum of more than 3 months, thus the main objective was
      to identify the prevalence of persistent PLBP and PGP as well as the differences
      over time in regard to pain status, self-rated health (SRH) and family situation
      at 12 months postpartum. METHODS: The study is a 12 month follow-up of a cohort
      of pregnant women developing PLBP and PGP during pregnancy, and who experienced
      persistent pain at 6 month follow-up after pregnancy. Women reporting PLBP/PGP (n
      = 639) during pregnancy were followed up with a second questionnaire at
      approximately six month after delivery. Women reporting recurrent or persistent
      LBP/PGP at the second questionnaire (n = 200) were sent a third questionnaire at
      12 month postpartum. RESULTS: A total of 176 women responded to the
      questionnaire. Thirty-four women (19.3%) reported remission of LBP/PGP, whereas
      65.3% (n = 115) and 15.3% (n = 27), reported recurrent LBP/PGP or continuous
      LBP/PGP, respectively. The time between base line and the 12 months follow-up was
      in actuality 14 months. Women with previous LBP before pregnancy had an increased
      odds ratio (OR) of reporting 'recurrent pain' (OR = 2.47) or 'continuous pain'
      (OR = 3.35) postpartum compared to women who reported 'no pain' at the follow-up.
      Women with 'continuous pain' reported statistically significant higher level of
      pain at all measure points (0, 6 and 12 months postpartum). Non-responders were
      found to report a statistically significant less positive scoring regarding
      relationship satisfaction compared to responders. CONCLUSIONS: The results from
      this study demonstrate that persistent PLBP/PGP is a major individual and public
      health issue among women 14 months postpartum, negatively affecting their self
      reported health. However, the perceived relationship satisfaction seems to be
      stable between the groups.

PMID- 24460729
TI  - Metapopulation persistence and species spread in river networks.
AB  - River networks define ecological corridors characterised by unidirectional
      streamflow, which may impose downstream drift to aquatic organisms or affect
      their movement. Animals and plants manage to persist in riverine ecosystems,
      though, which in fact harbour high biological diversity. Here, we study
      metapopulation persistence in river networks analysing stage-structured
      populations that exploit different dispersal pathways, both along-stream and
      overland. Using stability analysis, we derive a novel criterion for
      metapopulation persistence in arbitrarily complex landscapes described as spatial
      networks. We show how dendritic geometry and overland dispersal can promote
      population persistence, and that their synergism provides an explanation of the
      so-called 'drift paradox'. We also study the geography of the initial spread of a
      species and place it in the context of biological invasions. Applications
      concerning the persistence of stream salamanders in the Shenandoah river, and the
      spread of two invasive species in the Mississippi-Missouri are also discussed. 

PMID- 24460728
TI  - Procalcitonin predicts mortality in HIV-infected Ugandan adults with lower
      respiratory tract infections.
AB  - BACKGROUND AND OBJECTIVE: In low and middle-income countries where HIV infection
      is prevalent, identifying patients at high risk of dying from lower respiratory
      tract infections is challenging and validated prognostic models are lacking.
      Serum procalcitonin may be a useful prognostic tool in these settings. We sought
      to determine if elevated serum procalcitonin is associated with increased in
      hospital mortality and to combine serum procalcitonin with available clinical
      characteristics to create a clinically useful prognostic model. METHODS: We
      conducted a prospective, nested case-control study of 241 HIV-infected adults
      admitted to Mulago Hospital in Kampala, Uganda with cough >=2 weeks in duration.
      We collected demographic and clinical information, baseline serum for
      procalcitonin analysis, and followed patients to determine in-hospital mortality.
      RESULTS: Serum procalcitonin was a strong and independent predictor of inpatient
      mortality (aOR = 7.69, p = 0.01, sensitivity = 93%, negative predictive value =
      97%). Best subset multivariate analysis identified 3 variables that were combined
      into a prognostic model to risk stratify patients; these variables included
      respiratory rate >=30 breaths/minute (aOR = 2.07, p = 0.11), oxygen saturation
      <90% (aOR = 3.07, p = 0.02), and serum procalcitonin >0.5 ng/ml (aOR = 7.69, p =
      0.01). The predicted probability of inpatient mortality ranged from 1% when no
      variables were present, to 42% when all variables were present. CONCLUSIONS:
      Elevated serum procalcitonin >0.5 ng/ml is an independent predictor of in
      hospital mortality. Elevated serum procalcitonin, tachypnea, and hypoxemia may be
      combined into a prognostic model to identify patients at high risk of dying in
      the hospital. This model may be used to estimate the probability of death and to
      guide triage and treatment decisions.

PMID- 24460730
TI  - Characteristics of sebaceous carcinoma and early outcomes of treatment using Mohs
      micrographic surgery versus wide local excision: an update of the Mayo Clinic
      experience over the past 2 decades.
AB  - BACKGROUND: Sebaceous carcinoma (SC) is a rare cutaneous neoplasm. OBJECTIVE: To
      characterize SC and treatment approaches and outcomes. METHODS AND MATERIALS: We
      retrospectively reviewed records of patients with SC from 1992 through 2012.
      Recurrence-free survival was estimated and compared between groups. RESULTS: We
      identified 52 patients with SC (39, 75.0% male). Mean age +/- standard deviation
      at diagnosis was 72.7 +/- 10.8. Forty-nine patients (94.2%) were white. Twenty
      one (of 29 with known status) had a diagnosis of Muir-Torre syndrome. Six had
      multiple primary SCs (total of 73 SCs in 52 patients). The most common locations
      for SC were the back (20.5%), cheek (13.7%), nose (11.0%), and eye (9.6%).
      Treatment was recorded for 70 SCs; 35 (50.0%) were treated using Mohs
      micrographic surgery (MMS) and 26 (37.1%) using wide local excision (WLE). Of the
      45 patients (66 SCs) with clinical follow-up, three (6.7% of patients; 4.8% of
      SCs) had documented recurrence. CONCLUSION: MMS and WLE are effective treatments
      for SC. Further research is warranted to determine whether one treatment is more
      efficacious than the other.

PMID- 24460732
TI  - A comparison of home care quality indicator rates in two Canadian provinces.
AB  - BACKGROUND: Home care is becoming an increasingly vital sector in the health care
      system yet very little is known about the characteristics of home care clients
      and the quality of care provided in Canada. We describe these clients and
      evaluate home care quality indicator rates in two regions. METHODS: A cross
      sectional analysis of assessments completed for older (age 65+) home care clients
      in both Ontario (n = 102,504) and the Winnipeg Regional Health Authority (n =
      9,250) of Manitoba, using the Resident Assessment Instrument for Home Care (RAI
      HC). This assessment has been mandated for use in these two regions and the
      indicators are generated directly from items within the assessment. The
      indicators are expressed as rates of negative outcomes (e.g., falls,
      dehydration). Client-level risk adjustment of the indicator rates was used to
      enable fair comparisons between the regions. RESULTS: Clients had a mean age of
      83.2 years, the majority were female (68.6%) and the regions were very similar on
      these demographic characteristics. Nearly all clients (92.4%) required full
      assistance with instrumental activities of daily living (IADLs), approximately
      35% had activities of daily living (ADL) impairments, and nearly 50% had some
      degree of cognitive impairment, which was higher among clients in Ontario (48.8%
      vs. 37.0%). The highest quality indicator rates were related to clients who had
      ADL/rehabilitation potential but were not receiving therapy (range: 66.8%-91.6%)
      and the rate of cognitive decline (65.4%-76.3%). Ontario clients had higher
      unadjusted rates across 18 of the 22 indicators and the unadjusted differences
      between the two provinces ranged from 0.6% to 28.4%. For 13 of the 19 indicators
      that have risk adjustment, after applying the risk adjustment methodology, the
      difference between the adjusted rates in the two regions was reduced.
      CONCLUSIONS: Home care clients in these two regions are experiencing a
      significant level of functional and cognitive impairment, health instability and
      daily pain. The quality indicators provide some important insight into variations
      between the two regions and can serve as an important decision-support tool for
      flagging potential quality issues and isolating areas for improvement.

PMID- 24460731
TI  - Patterning expression of regenerative growth factors using high intensity focused
      ultrasound.
AB  - Temporal and spatial control of growth factor gradients is critical for tissue
      patterning and differentiation. Reinitiation of this developmental program is
      also required for regeneration of tissues during wound healing and tissue
      regeneration. Devising methods for reconstituting growth factor gradients remains
      a central challenge in regenerative medicine. In the current study we develop a
      novel gene therapy approach for temporal and spatial control of two important
      growth factors in bone regeneration, vascular endothelial growth factor, and bone
      morphogenetic protein 2, which involves application of high intensity focused
      ultrasound to cells engineered with a heat-activated- and ligand-inducible gene
      switch. Induction of transgene expression was tightly localized within cell
      scaffold constructs to subvolumes of ~30 mm3, and the amplitude and projected
      area of transgene expression was tuned by the intensity and duration of
      ultrasound exposure. Conditions for ultrasound-activated transgene expression
      resulted in minimal cytotoxicity and scaffold damage. Localized regions of growth
      factor expression also established gradients in signaling activity, suggesting
      that patterns of growth factor expression generated by this method will have
      utility in basic and applied studies on tissue development and regeneration.

PMID- 24460733
TI  - Effective salvage therapy for high-risk relapsed or refractory acute myeloid
      leukaemia with cisplatin in combination with high-dose cytarabine and etoposide.
AB  - OBJECTIVES: This study aimed at evaluating the efficacy and toxicity of the
      combination regimen of high-dose cytarabine, etoposide and cisplatin (HAEP) in
      adult patients with high-risk relapsed or refractory acute myeloid leukaemia
      (AML). METHODS: From January 2001 to December 2012, 49 relapsed or refractory AML
      patients [36 men; 13 women; median age, 42 (range, 18-71) yr; patients aged >60
      yr, 8] were treated with HAEP [high-dose cytarabine (2 g/m(2) ), etoposide (100
      mg/m(2) ) and cisplatin (20 mg/m(2) ) for five alternative days] as salvage
      therapy. Patients who had the first relapse at <6 months after an initial
      complete remission (CR), had a second or subsequent relapse, were primary
      refractory to >=2 courses of front-line conventional induction chemotherapy or
      were refractory to re-induction chemotherapy after any relapse was eligible for
      HAEP treatments. RESULTS: The overall CR + CR without platelet recovery (CRp)
      rates among 49 evaluable patients were 31% [95% confidence interval (CI), 17
      44%]. Of the eight patients aged >=60 yr, none showed any response to HAEP
      treatment. The CR + CRp rate was 54% in patients with second or greater relapse
      and 25% in patients refractory to re-induction therapy after relapse. In
      multivariate analysis, younger age, favourable cytogenetics and no prior salvage
      chemotherapy were independent predictors for better responses. CONCLUSION: Our
      findings suggest that HAEP is an effective salvage chemotherapy for patients aged
      <60 yr with high-risk relapsed or refractory AML.

PMID- 24460735
TI  - Engineering of pre-vascularized urethral patch with muscle flaps and hypoxia
      activated hUCMSCs improves its therapeutic outcome.
AB  - Tissue engineering has brought new hopes for urethral reconstruction. However,
      the absence of pre-vascularization and the subsequent degradation of materials
      often lead to the failure of in vivo application. In this study, with the
      assistance of hypoxia-activated human umbilical cord mesenchymal stem cells
      (hUCMSCs), pedicled muscle flaps were used as materials and pre-incubated in
      ventral penile subcutaneous cavity of rabbit for 3 weeks to prepare a pre
      vascularized urethral construct. We found that small vessels and muscle fibres
      were scattered in the construct after 3 weeks' pre-incubation. The construct
      presented a fibrous reticular structure, which was similar to that of the corpus
      spongiosum under microscope examination. The produced constructs were then used
      as a patch graft for reconstruction of the defective rabbit urethra (experimental
      group), natural muscular patch was used as control (control group). Twelve weeks
      after the reconstructive surgery, urethrography and urethroscope inspections
      showed wide calibres of the reconstructed urethra in the experimental group.
      Histopathological studies revealed that fibrous connective tissues and abundant
      muscle fibres constituted the main body of the patch-grafted urethra. In
      contrast, in the control group, only adipose tissue was found in the stenosis
      reconstructed urethra, replacing the originally grafted muscular tissue. To our
      knowledge, this is the first report that successfully constructed a pre
      vascularized urethral construct by using hypoxia-activated hUCMSC and pedicled
      muscle flaps. More importantly, the pre-vascularized construct showed a good
      performance in urethral reconstruction when applied in vivo. The study provided a
      novel strategy for tissue engineering of pre-vascularized urethral construct for
      the defective urethra, representing a further advancement in urethral
      reconstruction.

PMID- 24460734
TI  - Measuring midkine: the utility of midkine as a biomarker in cancer and other
      diseases.
AB  - Midkine (MK) is a pleiotropic growth factor prominently expressed during
      embryogenesis but down-regulated to neglible levels in healthy adults. Many
      published studies have demonstrated striking MK overexpression compared with
      healthy controls in various pathologies, including ischaemia, inflammation,
      autoimmunity and, most notably, in many cancers. MK expression is detectable in
      biopsies of diseased, but not healthy, tissues. Significantly, because it is a
      soluble cytokine, elevated MK is readily apparent in the blood and other body
      fluids such as urine and CSF, making MK a relatively convenient, accessible, non
      invasive and inexpensive biomarker for population screening and early disease
      detection. The first diagnostic tests that quantify MK are just now receiving
      regulatory clearance and entering the clinic. This review examines the current
      state of knowledge pertaining to MK as a biomarker and highlights promising
      indications and clinical settings where measuring MK could make a difference to
      patient treatment. I also raise outstanding questions about reported variants of
      MK as well as MK's bio-distribution in vivo. Answering these questions in future
      studies will enhance our understanding of the significance of measured MK levels
      in both patients and healthy subjects, and may reveal further opportunities for
      measuring MK to diagnose disease. MK has already proven to be a biomarker that
      can significantly improve detection, management and treatment of cancer, and
      there is significant promise for developing further MK-based diagnostics in the
      future.

PMID- 24460737
TI  - Twenty-four-hour rhythm of ocular perfusion pressure in non-arteritic anterior
      ischaemic optic neuropathy.
AB  - PURPOSE: In non-arteritic anterior ischaemic optic neuropathy (NAAION) patients,
      circulatory insufficiency within the optic nerve has previously been hypothesized
      to be related to nocturnal systemic hypotension. The main objective of this
      prospective cohort study was to investigate the nyctohemeral variations in ocular
      perfusion pressure (OPP) in NAAION patients. METHODS: In 20 patients with NAAION,
      the intraocular pressure (IOP) was measured using the Tono-Pen XL(TM) electronic
      tonometer every hour for 24 hr. Blood pressure (BP) was evaluated over 24 hr.
      Mean OPP was calculated with the following formula: OPP sitting position = (0.74
      * mean BP) - IOP and OPP lying position = (0.84 * mean BP) - IOP. A nonlinear
      least squares dual-harmonic regression analysis approach was used to model the 24
      hr rhythms of OPP data. RESULTS: On average, a 24-hr amplitude of 4.7 +/- 2.6
      mmHg was found for OPP. The patients were classified as either having a diurnal
      OPP rhythm (i.e. with a diurnal acrophase, 10% of the cases), a nocturnal OPP
      rhythm (45%) or absence of OPP rhythm (45%). Four patients had a nocturnal
      reduction in OPP (mean, -11%). CONCLUSION: The physiological nocturnal rhythm of
      OPP was maintained in 45% of the NAAION patients. The nocturnal reduction in OPP
      seen in 20% of the patients was within the range of OPP where optic nerve blood
      flow autoregulation is still fully operative. A high prevalence of obstructive
      sleep apnoea syndrome in our population (71%) may explain the low frequency of
      systemic nocturnal hypotension.

PMID- 24460736
TI  - Human maternal heritage in Andalusia (Spain): its composition reveals high
      internal complexity and distinctive influences of mtDNA haplogroups U6 and L in
      the western and eastern side of region.
AB  - BACKGROUND: The archeology and history of the ancient Mediterranean have shown
      that this sea has been a permeable obstacle to human migration. Multiple cultural
      exchanges around the Mediterranean have taken place with presumably population
      admixtures. A gravitational territory of those migrations has been the Iberian
      Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by
      means of control region sequencing and PCR-RFLP typing, of autochthonous
      Andalusians originating from the coastal provinces of Huelva and Granada, located
      respectively in the west and the east of the region. RESULTS: The mtDNA
      haplogroup composition of these two southern Spanish populations has revealed a
      wide spectrum of haplogroups from different geographical origins. The registered
      frequencies of Eurasian markers, together with the high incidence and
      diversification of African maternal lineages (15% of the total mitochondrial
      variability) among Huelva Andalusians when compared to its eastwards relatives of
      Granada and other Iberian populations, constitute relevant findings unknown up-to
      date on the characteristics of mtDNA within Andalusia that testifies a female
      population substructure. Therefore, Andalusia must not be considered a single,
      unique population. CONCLUSIONS: The maternal legacy among Andalusians reflects
      distinctive local histories, pointing out the role of the westernmost territory
      of Peninsular Spain as a noticeable recipient of multiple and diverse human
      migrations. The obtained results underline the necessity of further research on
      genetic relationships in both sides of the western Mediterranean, using carefully
      collected samples from autochthonous individuals. Many studies have focused on
      recent North African gene flow towards Iberia, yet scientific attention should be
      now directed to thoroughly study the introduction of European genes in northwest
      Africa across the sea, in order to determine its magnitude, timescale and
      methods, and to compare them to those terrestrial movements from eastern Africa
      and southwestern Asia.

PMID- 24460738
TI  - Health-related quality of life in adolescents with chronic physical illness in
      northern Russia: a cross-sectional study.
AB  - BACKGROUND: Health related quality of life (HRQoL) is an important subjectively
      evaluated outcome of adolescents physical, mental, and social functioning. It
      gives us the possibility to assess the disease impact on life of adolescents, and
      to sort out target groups of adolescents for future psychological interventions.
      The objective of this cross-sectional survey was to study HRQoL in 173
      adolescents with chronic physical illness (CPI - diabetes, asthma, and epilepsy),
      and to find HRQoL predictors in each disease group. METHODS: Disease-specific
      questionnaires were completed by each adolescent recruited from the local
      outpatient clinic; mothers answered the questions on socioeconomic status (SES);
      and the patients' clinicians evaluated the severity of the disease. RESULTS: A
      high proportion of adolescents in each disease specific sample reported moderate
      to high levels of HRQoL. Gender was the most prominent predictor of HRQoL in all
      three studied groups, while disease severity predicted HRQoL in the diabetic
      group and to some extent in the asthma group. CONCLUSIONS: Our results provide
      evidence that adolescents with diabetes, asthma, and epilepsy in northern Russia
      maintain relatively moderate to high levels of HRQoL. The domains affecting HRQoL
      were related to both disease-specific (severity) and non-disease factors (gender
      and SES). Our study suggests that future psychosocial interventions should focus
      on aspects of CPI impacting adolescents in gendered ways, furthermore taking into
      account disease specific factors.

PMID- 24460740
TI  - Extrusion of amyloid fibrils to the extracellular space in experimental mesangial
      AL-amyloidosis: transmission and scanning electron microscopy studies and
      correlation with renal biopsy observations.
AB  - In vitro studies have provided much information regarding the process of
      glomerular AL-amyloidogenesis. Research efforts have been successful in
      deciphering how glomerulopathic light chains interact with mesangial cells. The
      sequential steps involved in the genesis of amyloid fibrils include interactions
      with surface caveolae in mesangial cells and internalization of the monoclonal
      light chains through a clathrin-mediated process followed by trafficking in the
      mesangial cells to the mature lysosomal compartment where fibrils are formed.
      This manuscript focuses on how mesangial cells, once amyloid has been formed,
      deliver the fibrils to the extracellular matrix. The delivery of amyloid fibrils
      to the outside of the cells is carried out by lysosomes, which abut the mesangial
      cell membranes and extrude their contents into the extracellular space. This
      final step responsible for the fibrils to be present predominantly in the
      extracellular space is well demonstrated with scanning electron microscopy.

PMID- 24460739
TI  - Granulocyte colony-stimulating factor-producing lung cancer and acute respiratory
      distress syndrome.
AB  - Granulocyte colony-stimulating factor (G-CSF)-producing lung cancers are known to
      cause extreme leukocytosis. However, acute respiratory distress syndrome (ARDS)
      caused by G-CSF-producing lung cancer is extremely rare. We present a case of G
      CSF-producing lung cancer with marked leukocytosis, which rapidly led to severe
      ARDS after the patient developed pneumonia. The present case suggests that
      extreme leukocytosis may easily lead to ARDS, triggered by infection. Thus, G-CSF
      producing lung cancer with marked leukocytosis should be carefully monitored
      before surgery and during treatment. 

PMID- 24460741
TI  - Immigrants are attracted by local pre-breeders and recruits in a seabird colony.
AB  - Immigration is a major demographic factor shaping population dynamics. However,
      due to methodological difficulties, the extent of immigration and factors
      affecting immigration are insufficiently studied. This is also true for seabird
      colonies. We estimated annual immigration based on a long-term study of a colony
      of common terns Sterna hirundo marked with transponders, using a Bayesian
      integrated population model that links colony size and productivity with
      individual life histories. Strong annual fluctuations in the number of immigrants
      were found. To identify whether colony-specific covariates influenced
      immigration, we related the number of immigrants to various proxy variables for
      breeding site quality, specifically colony size, productivity, number of local
      subadults and local recruits. Numbers of local recruits and local subadults
      showed strong positive correlations with number of immigrants. We found that
      variation in immigration rate had strongly contributed to variation in colony
      growth rate, more so than variation in local recruitment or adult survival.
      Collectively, results suggest that immigration strongly affects colony growth
      rate, that the driving force behind immigration is natal dispersal and that
      immigrants were attracted by local recruits. 

PMID- 24460742
TI  - Development of a rectal sexually transmitted infection--HIV coinfection model
      utilizing Chlamydia trachomatis and SHIVSF162p3.
AB  - BACKGROUND: Rectal sexually transmitted infections (STIs) may increase HIV
      susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is
      prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we
      first evaluated whether cynomolgus macaques can sustain both C. trachomatis and
      SHIVSF162p3 infections. METHODS: Four SHIVSF162p3 -positive male cynomolgus
      macaques were used (n = 3 rectally inoculated with 10(6) IFU; n = 1 control).
      Systemic and rectal SHIV RNA levels and cytokines were measured by real-time PCR
      and Luminex assays, respectively. RESULTS: Macaques were successfully Chlamydia
      infected. Rectal SHIV shedding (P = 0.02 chi(2) ) and levels of G-CSF, IL-1ra, IL
      6, IL-8, IFN-gamma, and TNF-alpha (P <= 0.01, Mann-Whitney) in rectal secretions
      increased following infection. CONCLUSIONS: These pilot data successfully
      demonstrate rectal C. trachomatis-SHIV coinfection in cynomolgus macaques and
      suggest the feasibility of a rectal C. trachomatis model for SHIV susceptibility
      and biomedical prevention studies in the context of rectal STIs.

PMID- 24460743
TI  - Cardiovascular fitness is impaired in children born small for gestational age.

PMID- 24460744
TI  - Pericellular oxygen monitoring with integrated sensor chips for reproducible cell
      culture experiments.
AB  - OBJECTIVES: Here we present an application, in two tumour cell lines, based on
      the Sensing Cell Culture Flask system as a cell culture monitoring tool for
      pericellular oxygen sensing. MATERIALS AND METHODS: T-47D (human breast cancer)
      and T98G (human brain cancer) cells were cultured either in atmospheric air or in
      a glove-box set at 4% oxygen, in both cases with 5% CO2 in the gas phase.
      Pericellular oxygen tension was measured with the help of an integrated sensor
      chip comprising oxygen sensor arrays. RESULTS: Obtained results illustrate
      variation of pericellular oxygen tension in attached cells covered by stagnant
      medium. Independent of incubation conditions, low pericellular oxygen
      concentration levels, usually associated with hypoxia, were found in dense cell
      cultures. CONCLUSIONS: Respiration alone brought pericellular oxygen
      concentration down to levels which could activate hypoxia-sensing regulatory
      processes in cultures believed to be aerobic. Cells in culture believed to
      experience conditions of mild hypoxia may, in reality, experience severe hypoxia.
      This would lead to incorrect assumptions and suggests that pericellular oxygen
      concentration readings are of great importance to obtain reproducible results
      when dealing with hypoxic and normoxic (aerobic) incubation conditions. The
      Sensing Cell Culture Flask system allows continuous monitoring of pericellular
      oxygen concentration with outstanding long-term stability and no need for
      recalibration during cell culture experiments. The sensor is integrated into the
      flask bottom, thus in direct contact with attached cells. No additional equipment
      needs to be inserted into the flask during culturing. Transparency of the
      electrochemical sensor chip allows optical inspection of cells attached on top of
      the sensor.

PMID- 24460745
TI  - Office design's impact on sick leave rates.
AB  - The effect of office type on sickness absence among office employees was studied
      prospectively in 1852 employees working in (1) cell-offices; (2) shared-room
      offices; (3) small, (4) medium-sized and (5) large open-plan offices; (6) flex
      offices and (7) combi-offices. Sick leaves were self-reported two years later as
      number of (a) short and (b) long (medically certified) sick leave spells as well
      as (c) total number of sick leave days. Multivariate logistic regression analysis
      was used, with adjustment for background factors. A significant excess risk for
      sickness absence was found only in terms of short sick leave spells in the three
      open-plan offices. In the gender separate analysis, this remained for women,
      whereas men had a significantly increased risk in flex-offices. For long sick
      leave spells, a significantly higher risk was found among women in large open
      plan offices and for total number of sick days among men in flex-offices.
      PRACTITIONER SUMMARY: A prospective study of the office environment's effect on
      employees is motivated by the high rates of sick leaves in the workforce. The
      results indicate differences between office types, depending on the number of
      people sharing workspace and the opportunity to exert personal control as
      influenced by the features that define the office types.

PMID- 24460747
TI  - Histologic study of collagen and stem cells after radiofrequency treatment for
      aging skin.
AB  - BACKGROUND: Monopolar radiofrequency (mRF) devices have been shown to be
      clinically effective for treating aging skin, but there are few histologic
      studies about the mechanisms. OBJECTIVE: To histologically analyze chronologic
      and quantitative change in collagens after mRF treatment to determine the
      mechanisms of the antiaging effect. METHODS: Five patients were enrolled in this
      study. Skin specimens were taken before and 1 and 3 months after treatment.
      Immunostaining was performed to determine change in type I and III collagen
      levels and stem and other cell counts in skin layers. RESULTS: In all cases, both
      types of collagen significantly increased after irradiation in the dermis (p <
      .05), and their changes were noticed uniformly in all layers. No significant
      change was noticed in stem and other cell counts. CONCLUSIONS: This study
      histologically demonstrated that type I and III collagen increased significantly
      in the dermis after mRF treatment. The amount of stem cells did not affect the
      increase in collagens.

PMID- 24460746
TI  - Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over
      5 years of therapy in a phase 3b and subsequent postmarketing observational
      study.
AB  - INTRODUCTION: Patients with active rheumatoid arthritis who had failed at least
      one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab
      (ADA) in the ReAct study with the option to continue treatment for 5 years in
      ReAlise. The purpose of this study was to evaluate the long-term safety and
      effectiveness of ADA as prescribed from the first injection in ReAct to the last
      observation in ReAlise. METHODS: Patients received ADA alone or in combination
      with DMARDs according to usual clinical care practices. Adverse events (AEs) were
      tabulated by five time windows after the first ADA injection. Effectiveness
      measures included achievement of low disease activity (LDA), defined as
      Simplified Disease Activity Index (SDAI) <=11, or remission, (REM), defined as
      SDAI <=3.3. RESULTS: Of the 6,610 ReAct patients, 3,435 (52%) continued in
      ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean
      HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272
      patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and
      serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious
      AEs occurred most frequently in the first 6 months and deceased thereafter.
      Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised
      incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved
      by 50% and REM by 21% of patients at last observation. CONCLUSIONS: Results of
      this large observational study of ADA in routine clinical practice were
      consistent with controlled trials, with no new safety concerns during a follow-up
      of more than 5 years. Effectiveness of ADA was maintained during long-term
      observation. TRIAL REGISTRATION: NCT00448383, NCT00234884.

PMID- 24460748
TI  - A randomized clinical trial comparing guided implant surgery (bone- or mucosa
      supported) with mental navigation or the use of a pilot-drill template.
AB  - AIM: To assess the accuracy of guided surgery (mucosa and bone-supported)
      compared to mental navigation or the use of a surgical template, in fully
      edentulous jaws, in a randomized controlled study. MATERIAL AND METHODS: Fifty
      nine patients (72 jaws), requiring four to six implants (maxilla or mandible),
      were consecutively recruited and randomly assigned to one of the following
      treatment groups; guidance via Materialise Universal((r))/mucosa, Materialise
      Universal((r))/bone, FacilitateTM/mucosa, FacilitateTM/bone, or mental navigation
      or a pilot-drill template. The precision was assessed by matching the planning
      computed tomography (CT) with a post-operative cone beam CT. RESULTS: A
      significant lower mean deviation at the entry point (1.4 mm, range: 0.3-3.7), at
      the apex (1.6 mm, range: 0.2-3.7) and angular deviation (3.0 degrees , range: 0.2
      16 degrees ) was observed for the guiding systems when compared to mental
      navigation (2.7 mm, range: 0.3-8.3; 2.9 mm, range: 0.5-7.4 and 9.9 degrees ,
      range: 1.5-27.8) and to the surgical template group (3.0 mm, range: 0.6-6.6; 3.4
      mm, range: 0.3-7.5 and 8.4 degrees , range: 0.6-21.3 degrees ). Differences
      between bone and mucosa support or type of guidance were negligible. Jaw and
      implant location (posterior-anterior, left-right), however, had a significant
      influence on the accuracy when guided. CONCLUSION: Based on these findings,
      guided implant placement appears to offer clear accuracy benefits.

PMID- 24460749
TI  - Microvascular invasion (MVI) is a poorer prognostic predictor for small
      hepatocellular carcinoma.
AB  - BACKGROUND: Small hepatocellular carcinoma (SHCC) is a special type of
      hepatocellular carcinoma with the maximum tumor diameter <= 3 cm and excellent
      long-term outcomes. However, the prognostic factors for SHCC remain
      controversial. The purpose of this study is to clarify the predictive factors of
      SHCC. METHODS: The study population consisted of 458 patients underwent
      hepatectomy for single SHCC between January 2006 and December 2008. Clinical data
      (included age, gender, virus infection, serum alfa-fetoprotein level, cirrhosis,
      capsule, border), histopathologic features (included differentiation, morphology
      subtype, microvascular invasion, tumor infiltrative lymphocytes (TIL),
      inflammatory injury grade and fibrosis stage of surrounding liver), were
      evaluated to identify prognostic factors influencing SHCC patients' survival and
      microvascular invasion. RESULTS: There were 384 males (83.8%) and 74 (16.2%)
      females with median ages of 52 years. The median progression-free survival (PFS)
      and overall survival (OS) durations were 53 and 54 months, respectively. About
      91.9% (n = 421) SHCC were infected by Hepatitis B. One hundred forty-seven of the
      446 (33.0%) patients with pre-operation serum AFP level record had serum alfa
      fetoprotein (AFP) level >= 200 ug/ml and 178 of the 280 (63.8%) patients with
      post-operation serum AFP level record had AFP level >= 20 ug/ml. Liver cirrhosis
      was present in 411 cases (89.7%), while 434 (97.3%) tumors had clear border, and
      250 (55.6%) tumors were encapsulated.MVI was identified in 83 patients (18.1%).
      In univariate analysis, a significant association between the presence of MVI and
      shortened PFS and OS was found (p = 0.012, 0.028, respectively). Histological
      differentiation had strong relationship with MVI (p = 0.009), in terms of MVI was
      more easily presented in patients with worse histological differentiation. In
      patients with MVI, worse survival was correlated with female patients, patients
      with G2 or G3 histological differentiation, pre-operation serum AFP level >= 200
      ug/ml or post-operation serum AFP level >= 20 ug/ml, and TIL >= 50/HPF.
      CONCLUSIONS: MVI is an independent poorer prognostic factor for PFS and OS of
      single SHCC patients. Tumor histological differentiation was closely related with
      MVI.

PMID- 24460750
TI  - External validation and clinical evaluation of the International Prognostic Score
      of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) in a large cohort
      of Chinese patients.
AB  - OBJECTIVES: In patients with essential thrombocythemia (ET), vascular
      complications contribute to both morbidity and mortality. To better predict the
      occurrence of thrombotic events, an International Prognostic Score of thrombosis
      for ET (IPSET-thrombosis) was recently developed. We hereby presented an external
      validation and analysis of this model in a large Cohort of Chinese Patients.
      METHODS: We retrospectively evaluated the characteristics and risk factors for
      thrombosis in 970 Chinese patients with ET and estimated the clinical
      implications of the IPSET-thrombosis model. RESULTS: The median follow-up was 49
      months (range, 0-360). Chinese ET patients had similar clinical characteristics
      as Caucasian patients. Similar to the IPSET-thrombosis study, our multivariate
      analysis revealed age >60 (HR = 1.949), previous thrombosis (HR = 2.484),
      JAK2V617F mutation (HR = 1.719), and cardiovascular risk factors (HR = 1.877) as
      independent risk factors for thrombosis. We confirmed that the above risk factors
      in IPSET-thrombosis, when compared with traditional risk factors (e.g., age >=60
      and previous thrombotic events), were more predictive of thrombotic events (C
      index 0.714 vs. 0.647). Classification by IPSET-thrombosis risk groups revealed
      different cumulative thrombosis-free survival (P < 0.001). For treatment,
      patients in the intermediate- and high-risk group derived clinical benefit from
      cytoreductive agents (P < 0.05), but those in the low-risk group did not (P =
      0.446). The lower risk of thrombosis on cytoreductive therapy was related to
      decrease in leukocyte count during the disease course. CONCLUSIONS: We validate
      the reproducibility of IPSET-thrombosis in Chinese ET patients and provide key
      clinical implications.

PMID- 24460751
TI  - Poor sleep quality and obstructive sleep apnea in patients with GERD and
      Barrett's esophagus.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) reduces sleep quality. Whether
      Barrett's esophagus (BE) affects sleep differently is unknown. Obstructive sleep
      apnea (OSA) often coexists with GERD and may disrupt sleep; whether GERD reduces
      sleep quality independently of OSA is unknown. Our aims were to compare the
      effect of GERD and BE on sleep quality, and assess the impact of OSA on this
      association. METHODS: Validated questionnaires for GERD symptoms, sleep quality,
      and OSA risk were prospectively administered to subjects undergoing upper
      endoscopy. GERD was defined by erosive esophagitis and/or reflux symptoms
      >1/week. BE was defined histologically. Controls had normal endoscopy and were
      asymptomatic. Poor sleep quality was defined by a Pittsburgh Sleep Quality Index
      score >5. Risk of OSA was defined by a positive Berlin Questionnaire. The risk
      poor sleep quality in GERD, BE, and controls was evaluated in multivariate
      models. KEY RESULTS: 83 GERD, 63 BE, and 75 controls were included. OSA and poor
      sleep quality were significantly more frequent in GERD (65% and 60%) but not BE
      (52% and 46%) compared with controls (48% and 39%). Controlling for age, race,
      gender, smoking, body mass index, and hypertension, the risk of poor sleep
      quality was significantly increased in GERD compared with controls (odds ratio
      [OR] = 2.79, 95% confidence interval [CI]: 1.08-6.80), significance was lost
      after adding OSA to the model (OR = 2.27, 95% CI: 0.87-5.85). CONCLUSIONS &
      INFERENCES: GERD but not BE increases the risk of poor sleep quality. This
      association is not independent of OSA.

PMID- 24460752
TI  - First detection of Leishmania infantum (Kinetoplastida: Trypanosomatidae) in
      Culicoides spp. (Diptera: Ceratopogonidae).
AB  - BACKGROUND: Culicoides (Diptera: Ceratopogonidae) species are known to be the
      vectors of Bluetongue virus and African Horses Sickness virus (AHSV) in different
      areas of the world. Nevertheless, other researchers have hypothesized that these
      arthropods could be involved in the transmission of other pathogens such as
      Schmallenberg virus, Plasmodium and Leishmania parasites. Identification of the
      Culicoides' potential vector competence is crucial in understanding the worldwide
      Culicoides/Leishmania life cycle. FINDINGS: Blood fed and parous females of
      biting midges Culicoides spp. were collected between 2009 and 2010 in Central
      Tunisia. DNA was extracted from individual blood fed Culicoides and used as a
      template in a genus-specific PCR. Leishmania DNA was detected in 14 Culicoides
      imicola specimens and one Culicoides circumscriptus. In a second step, parasite
      identification was performed based on a single copy Topo-isomerase II gene
      specific amplification and sequencing. Leishmania infantum was identified in two
      infected Culicoides spp. CONCLUSION: This is the first report of Leishmania DNA
      detection from naturally infected wild caught Culicoides spp. Our finding
      supports the assumption that Culicoides spp. are a potential vector for L.
      infantum.

PMID- 24460753
TI  - Menthol enhances phasic and tonic GABAA receptor-mediated currents in midbrain
      periaqueductal grey neurons.
AB  - BACKGROUND AND PURPOSE: Menthol, a naturally occurring compound in the essential
      oil of mint leaves, is used for its medicinal, sensory and fragrant properties.
      Menthol acts via transient receptor potential (TRPM8 and TRPA1) channels and as a
      positive allosteric modulator of recombinant GABAA receptors. Here, we examined
      the actions of menthol on GABAA receptor-mediated currents in intact midbrain
      slices. EXPERIMENTAL APPROACH: Whole-cell voltage-clamp recordings were made from
      periaqueductal grey (PAG) neurons in midbrain slices from rats to determine the
      effects of menthol on GABAA receptor-mediated phasic IPSCs and tonic currents.
      KEY RESULTS: Menthol (150-750 MUM) produced a concentration-dependent
      prolongation of spontaneous GABAA receptor-mediated IPSCs, but not non-NMDA
      receptor-mediated EPSCs throughout the PAG. Menthol actions were unaffected by
      TRPM8 and TRPA1 antagonists, tetrodotoxin and the benzodiazepine antagonist,
      flumazenil. Menthol also enhanced a tonic current, which was sensitive to the
      GABAA receptor antagonists, picrotoxin (100 MUM), bicuculline (30 MUM) and Zn(2+)
      (100 MUM), but unaffected by gabazine (10 MUM) and a GABAC receptor antagonist,
      1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA; 50 MUM). In
      addition, menthol potentiated currents induced by the extrasynaptic GABAA
      receptor agonist THIP/gaboxadol (10 MUM). CONCLUSIONS AND IMPLICATIONS: These
      results suggest that menthol positively modulates both synaptic and extrasynaptic
      populations of GABAA receptors in native PAG neurons. The development of agents
      that potentiate GABAA -mediated tonic currents and phasic IPSCs in a manner
      similar to menthol could provide a basis for novel GABAA -related
      pharmacotherapies.

PMID- 24460754
TI  - Conditions that influence the impact of malpractice litigation risk on
      physicians' behavior regarding patient safety.
AB  - BACKGROUND: Practicing safe behavior regarding patients is an intrinsic part of a
      physician's ethical and professional standards. Despite this, physicians practice
      behaviors that run counter to patient safety, including practicing defensive
      medicine, failing to report incidents, and hesitating to disclose incidents to
      patients. Physicians' risk of malpractice litigation seems to be a relevant
      factor affecting these behaviors. The objective of this study was to identify
      conditions that influence the relationship between malpractice litigation risk
      and physicians' behaviors. METHODS: We carried out an exploratory field study,
      consisting of 22 in-depth interviews with stakeholders in the malpractice
      litigation process: five physicians, two hospital board members, five patient
      safety staff members from hospitals, three representatives from governmental
      healthcare bodies, three healthcare law specialists, two managing directors from
      insurance companies, one representative from a patient organization, and one
      representative from a physician organization. We analyzed the comments of the
      participants to find conditions that influence the relationship by developing
      codes and themes using a grounded approach. RESULTS: We identified four factors
      that could affect the relationship between malpractice litigation risk and
      physicians' behaviors that run counter to patient safety: complexity of care,
      discussing incidents with colleagues, personalized responsibility, and hospitals'
      response to physicians following incidents. CONCLUSION: In complex care settings
      procedures should be put in place for how incidents will be discussed, reported
      and disclosed. The lack of such procedures can lead to the shift and off-loading
      of responsibilities, and the failure to report and disclose incidents. Hospital
      managers and healthcare professionals should take these implications of
      complexity into account, to create a supportive and blame-free environment.
      Physicians need to know that they can rely on the hospital management after
      reporting an incident. To create realistic care expectations, patients and the
      general public also need to be better informed about the complexity and risks of
      providing health care.

PMID- 24460755
TI  - Detection and identification of oxidants formed during *NO/O2*- reaction: a multi
      well plate CW-EPR spectroscopy combined with HPLC analyses.
AB  - New techniques and probes are routinely emerging for detecting short-lived free
      radicals such as superoxide radical anion (O2(*-)), nitric oxide ((*)NO), and
      transient oxidants derived from peroxynitrite (ONOO(-)/ONOOH). Recently, we
      reported the profiles of oxidation products (2-hydroxyethidium, ethidium, and
      various dimeric products) of the fluorogenic probe hydroethidine (HE) in the
      (*)NO/O2(*-) system (Zielonka et al. 2012). In this study, we used HPLC analyses
      of HE oxidation products in combination with continuous wave electron
      paramagnetic resonance (CW-EPR) spin trapping with 5-tert-butoxycarbonyl-5-methyl
      1-pyrroline N-oxide (BMPO) to define the identity of the oxidizing species formed
      in the (*)NO/O2(*-) system. EPR spin-trapping technique is still considered as
      the gold standard for characterization of free radicals and their intermediates.
      We monitored formation of BMPO-superoxide (BMPO-(*)OOH) and BMPO-hydroxyl (BMPO
      (*)OH) radical adducts. Simultaneous analyses of results from EPR spin-trapping
      and HPLC measurements are helpful in the interpretation of the mechanism of
      formation of products of HE oxidation.

PMID- 24460757
TI  - High resolution structural changes of Schwann cell and endothelial cells in
      peripheral nerves across leprosy spectrum.
AB  - A systematic ultrastructure of peripheral nerves across the spectrum of leprosy
      was studied with an aim to better understanding the pathogenesis of nerve
      involvement in leprosy using light and electron microscope. The pathogenesis of
      nerve destruction varies in leprosy considerably along the spectrum. The study
      has begun to shed new light on some aspects of the infection of Mycobacterium
      leprae (M. lepare) and phenomenon has opened new avenue of research and possible
      mechanism of pathogenesis in TT/BT/BL/LL leprosy. In tuberculoid type (TT) and
      borderline tuberculoid (BT) leprosy, the degenerative changes of Schwann cells
      (SCs) and presence of perineural and perivascular cuffing by mononuclear cells.
      The endoneurial blood vessel (EBV) showed thickening of basement membrane with
      hypertrophy of EC leading to narrowing or complete occlusion of lumen and causing
      ischemia. However, borderline lepromatous (BL) and lepromatous leprosy (LL) foamy
      macrophages and vacuolated SC contain numerous small dense materials, irregular
      in shape and size was prominent and, considered to be degenerated and fragmented
      M. Leprae. The dense materials were also found in the cytoplasm of vascular EC.
      It was revealed that besides SC, the EC of EBV frequently harbor M. leprae in LL.
      The lumen of the EBV was wide open with enlarged nucleus. In the present study,
      the ultrastructural characteristics suggest that hypersensitivity mechanisms are
      possibly responsible for nerve damage in TT/BT leprosy. However, the study
      indicates that the mechanisms of nerve damage in BL/LL are basically different
      wherein hypersensitivity appears to play a very limited role.

PMID- 24460756
TI  - Cost-efficient high-throughput HLA typing by MiSeq amplicon sequencing.
AB  - BACKGROUND: A close match of the HLA alleles between donor and recipient is an
      important prerequisite for successful unrelated hematopoietic stem cell
      transplantation. To increase the chances of finding an unrelated donor,
      registries recruit many hundred thousands of volunteers each year. Many
      registries with limited resources have had to find a trade-off between cost and
      resolution and extent of typing for newly recruited donors in the past.
      Therefore, we have taken advantage of recent improvements in NGS to develop a
      workflow for low-cost, high-resolution HLA typing. RESULTS: We have established a
      straightforward three-step workflow for high-throughput HLA typing: Exons 2 and 3
      of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 are amplified by PCR on Fluidigm Access
      Array microfluidic chips. Illumina sequencing adapters and sample specific tags
      are directly incorporated during PCR. Upon pooling and cleanup, 384 samples are
      sequenced in a single Illumina MiSeq run. We developed "neXtype" for streamlined
      data analysis and HLA allele assignment. The workflow was validated with 1140
      samples typed at 6 loci. All neXtype results were concordant with the Sanger
      sequences, demonstrating error-free typing of more than 6000 HLA loci. Current
      capacity in routine operation is 12,000 samples per week. CONCLUSIONS: The
      workflow presented proved to be a cost-efficient alternative to Sanger sequencing
      for high-throughput HLA typing. Despite the focus on cost efficiency, resolution
      exceeds the current standards of Sanger typing for donor registration.

PMID- 24460758
TI  - Vascular considerations in glaucoma patients of African and European descent.
AB  - Glaucoma is the leading cause of blindness in individuals of African descent
      (AD). While open-angle glaucoma (OAG) disproportionately affects individuals of
      AD compared with persons of European descent (ED), the physiological mechanisms
      behind this disparity are largely unknown. The more rapid progression and greater
      severity of the disease in persons of AD further raise the concern for
      identifying these underlying differences in disease pathophysiology between AD
      and ED glaucoma patients. Ocular structural differences between AD and ED
      patients, including larger optic disc area, cup:disc ratio and thinner corneas,
      have been found. AD individuals are also disproportionately affected by systemic
      vascular diseases, including hypertension, cardiovascular disease, stroke and
      diabetes mellitus. Abnormal ocular blood flow has been implicated as a risk
      factor for glaucoma, and pilot research is beginning to identify localized ocular
      vascular differences between AD and ED OAG patients. Given the known systemic
      vascular deficits and the relationship between glaucoma and ocular blood flow,
      exploring these concepts in terms of glaucoma risk factors may have a significant
      impact in elucidating the mechanisms behind the disease disparity in the AD
      population. 

PMID- 24460760
TI  - The relationship between physical activity, functional performance and fatigue in
      sarcoidosis.

PMID- 24460759
TI  - Influence of type-I Interferon receptor expression level on the response to type
      I Interferons in human pancreatic cancer cells.
AB  - Pancreatic cancer is a highly aggressive malignancy with limited treatment
      options. Type-I interferons (e.g. IFN-alpha/-beta) have several anti-tumour
      activities. Over the past few years, clinical studies evaluating the effect of
      adjuvant IFN-alpha therapy in pancreatic cancer yielded equivocal results.
      Although IFN-alpha and -beta act via the type-I IFN receptor, the role of the
      number of receptors present on tumour cells is still unknown. Therefore, this
      study associated, for the first time, in a large panel of pancreatic cancer cell
      lines the effects of IFN-alpha/-beta with the expression of type-I IFN receptors.
      The anti-tumour effects of IFN-alpha or IFN-beta on cell proliferation and
      apoptosis were evaluated in 11 human pancreatic cell lines. Type-I IFN receptor
      expression was determined on both the mRNA and protein level. After 7 days of
      incubation, IFN-alpha significantly reduced cell growth in eight cell lines by 5
      67%. IFN-beta inhibited cell growth statistically significant in all cell lines
      by 43-100%. After 3 days of treatment, IFN-beta induced significantly more
      apoptosis than IFN-alpha. The cell lines variably expressed the type-I IFN
      receptor. The maximal inhibitory effect of IFN-alpha was positively correlated
      with the IFNAR-1 mRNA (P < 0.05, r = 0.63), IFNAR-2c mRNA (P < 0.05, r = 0.69)
      and protein expression (P < 0.05, r = 0.65). Human pancreatic cancer cell lines
      variably respond to IFN-alpha and -beta. The expression level of the type-I IFN
      receptor is of predictive value for the direct anti-tumour effects of IFN-alpha
      treatment. More importantly, IFN-beta induces anti-tumour effects already at much
      lower concentrations, is less dependent on interferon receptor expression and
      seems, therefore, more promising than IFN-alpha.

PMID- 24460761
TI  - Survey of medical student preference for simulation models for basic dermatologic
      surgery skills: simulation platforms in medical education.
AB  - BACKGROUND: The authors investigated the use of simulator platforms in fourth
      year medical student education. OBJECTIVE: To evaluate which simulation platform
      students preferred for learning dermatologic procedures and to assess the
      effectiveness of the exercise in terms of the change in confidence that the
      students had performing dermatologic procedures. MATERIALS AND METHODS: After
      medical students were instructed on how to perform a punch biopsy and then
      assisted in executing the task, they were surveyed to determine their preferred
      simulation platform and simulator properties. Students were surveyed at the
      beginning and completion of the teaching block. RESULTS: One hundred fifty-seven
      students completed the skills laboratory, and 78 completed the preference
      questionnaire. Of the 11 surveyed categories, students preferred the pig foot in
      eight categories. Seventy students responded to a surgical skills questionnaire
      that assessed their overall confidence in planning and executing the procedure
      before and after the skills laboratory. The students had a statistically
      significant increase in confidence in dermatologic procedural skills as a result
      of the activity. CONCLUSION: Preference data show that the pig foot model is
      preferred for teaching dermatologic surgical skills. These results re-affirm that
      the pig foot model is an effective, low-cost solution for training.

PMID- 24460762
TI  - Frontal alpha asymmetry and sexually motivated states.
AB  - Anterior alpha asymmetry of electroencephalographic (EEG) signals has been
      suggested to index state approach (or avoidance) motivation. This model has not
      yet been extended to high approach-motivation sexual stimuli, which may represent
      an important model of reward system function. Sixty-five participants viewed a
      neutral and a sexually motivating film while their EEG was recorded, and reported
      their sexual feelings after each film. Greater alpha power in the left hemisphere
      during sexually motivated states was evident. A positive relationship between
      self-reported mental sexual arousal and alpha asymmetry was identified, where
      coherence between these indicators was higher in women. Notably, coherence was
      stronger when mental versus physical sexual arousal was rated. Alpha asymmetry
      appears to offer a new method for further examining this novel coherence pattern
      across men and women. 

PMID- 24460763
TI  - Derivation, validation and comparative performance of a simplified chest X-ray
      score for assessing the severity and outcome of pulmonary tuberculosis.
AB  - INTRODUCTION: To derive and validate against the Ralph et al. score, a simplified
      chest X-ray (CXR) score (SCS) for predicting the outcome of smear-positive
      pulmonary tuberculosis (SPPTB) among patients with high prevalence of human
      immunodeficiency virus (HIV) infection. METHODS: CXR for 636 SPPTB patients (377
      men, median age 31 years) from the Yaounde Jamot Hospital (Cameroon) were
      examined for the presence of tuberculosis lesions, and estimation of the
      proportion of lungs affected. SPPTB's evolution was based on sputum smear
      examination after 2 months of treatments. Logistic regressions were used to
      derive the SCS with internal validation via bootstrap resampling. Receiver
      operating characteristic curves (AUC) analyses were used to validate, determine
      of the optimal cut-offs and compare models' performance. RESULTS: HIV co
      infection was present in 191 (30%) patients. Sputum smear non-conversion was
      found in 45 (7.1) patients after 2 months of treatment. The SCS was expressed as
      proportion of lung affected plus 23 if cavitation is present. The AUC (95%
      confidence interval) was 0.718 (0.640-0.795), with little variation in bootstrap
      validation, and no sizable difference from the Ralph et al. model [0.714 (0.633
      0.7860), P = 0.717 for the difference). Both models had good calibration (Hosmer
      Lemeshow P >= 0.183). The optimal cut-off for predicting non-conversion of the
      sputum at 2 months was 52 for the SCS (sensitivity/specificity 66.7%/62.8%) and
      74.5 (62.2%/74.3%) with Ralph et al. score. CONCLUSIONS: The outcome of SPPTB
      among patients with high prevalence of HIV can acceptably be predicted by simple
      scores comprising baseline CXR variables, including the Ralph et al. score and
      the SCS from this study.

PMID- 24460765
TI  - High-temperature adapted primitive Protochlamydia found in Acanthamoeba isolated
      from a hot spring can grow in immortalized human epithelial HEp-2 cells.
AB  - To elucidate how ancient pathogenic chlamydiae could overcome temperature
      barriers to adapt to human cells, we characterized a primitive chlamydia found in
      HS-T3 amoebae (Acanthamoeba) isolated from a hot spring. Phylogenetic analysis
      revealed the primitive species to be Protochlamydia. In situ hybridization
      staining showed broad distribution into the amoebal cytoplasm, which was
      supported by transmission electron microscopic analysis showing typical
      chlamydial features, with inclusion bodies including both elementary and
      reticular bodies. Interestingly, although most amoebae isolated from natural
      environments show reduced growth at 37 degrees C, the HS-T3 amoebae harbouring
      the Protochlamydia grew well at body temperature. Although infection with
      Protochlamydia did not confer temperature tolerance to the C3 amoebae, the number
      of infectious progenies rapidly increased at 37 degrees C with amoebal lysis. In
      immortalized human epithelial HEp-2 cells, fluorescence microscopic study
      revealed atypical inclusion of the Protochlamydia, and quantitative real-time
      polymerase chain reaction analyses also showed an increase in 16S ribosomal RNA
      DNA amounts. Together, these results showed that the Protochlamydia found in HS
      T3 amoebae isolated from a hot spring successfully adapted to immortalized human
      HEp-2 cells at 37 degrees C, providing further information on the evolution of
      ancient Protochlamydia to the present pathogenic chlamydiae. 

PMID- 24460764
TI  - Race/ethnicity and HAART initiation in a military HIV infected cohort.
AB  - BACKGROUND: Prior studies have suggested that HAART initiation may vary by
      race/ethnicity. Utilizing the U.S. military healthcare system, which minimizes
      confounding from healthcare access, we analyzed whether timing of HAART
      initiation and the appropriate initiation of primary prophylaxis among those at
      high risk for pneumocystis pneumonia (PCP) varies by race/ethnicity. METHODS:
      Participants in the U.S. Military HIV Natural History Study from 1998-2009 who
      had not initiated HAART before 1998 and who, based on DHHS guidelines, had a
      definite indication for HAART (CD4 <200, AIDS event or severe symptoms; Group A),
      an indication to consider HAART (including CD4 <350; Group B) or electively
      started HAART (CD4 >350; Group C) were analyzed for factors associated with HAART
      initiation. In a secondary analysis, participants were also evaluated for factors
      associated with starting primary PCP prophylaxis within four months of a CD4
      count <200 cells/mm3. Multiple logistic regression was used to compare those who
      started vs. delayed therapy; comparisons were expressed as odds ratios (OR).
      RESULTS: 1262 participants were evaluated in the analysis of HAART initiation (A
      = 208, B = 637, C = 479 [62 participants were evaluated in both Groups A and B];
      94% male, 46% African American, 40% Caucasian). Race/ethnicity was not associated
      with HAART initiation in Groups A or B. In Group C, African American
      race/ethnicity was associated with lower odds of initiating HAART (OR 0.49, p =
      0.04). Race and ethnicity were also not associated with the initiation of primary
      PCP prophylaxis among the 408 participants who were at risk. CONCLUSIONS: No
      disparities in the initiation of HAART or primary PCP prophylaxis according to
      race/ethnicity were seen among those with an indication for therapy. Among those
      electively initiating HAART at the highest CD4 cell counts, African American
      race/ethnicity was associated with decreased odds of starting. This suggests that
      free healthcare can potentially overcome some of the observed disparities in HIV
      care, but that unmeasured factors may contribute to differences in elective care
      decisions.

PMID- 24460766
TI  - Acute necrotizing colitis due to sigmoid colon cancer.
AB  - When obstructive colitis becomes fulminant, it is known as 'acute necrotizing
      colitis'. We report a rare case of acute necrotizing colitis due to sigmoid colon
      cancer, in which shock status occurred within ten hours of onset. A 79-year-old
      female with acute abdominal pain was transported to our hospital with acute
      shock. Abdominal enhanced computed tomography revealed thickening of the wall of
      the sigmoid colon and marked dilation of the proximal colon. Emergency surgery
      was performed with the intraoperative findings of severe sigmoid colon stenosis
      and proximal dilation of the colon without perforation, and a large volume of
      putrid ascitic fluid. The intestine was proximally dilated and black in color,
      from the sigmoid colon to the ileum 60 cm proximal to the terminal ileum,
      suggesting acute necrosis. Total colectomy with 80 cm resection of terminal ileum
      and ileostomy was performed. Whereas acute necrotizing colitis is a rare
      condition and its etiology remains obscure, the chronic ischemic state must play
      some role. Our patient was of advanced age and had diabetes mellitus and
      hypertension. These factors might lead to a chronic ischemic state of the bowel
      due to arteriosclerosis. In addition to the underlying condition, massive
      bacterial reflux into the ileum from the colon might cause the capillary
      vasoconstriction of the bowel that led to her critical state.

PMID- 24460768
TI  - Nonthermal inactivation of soy (Glycine max Sp.) lipoxygenase by pulsed
      ultraviolet light.
AB  - This study investigated pulsed ultraviolet (PUV) illumination at different
      distances from the PUV source on soybean lipoxygenase (LOX) (0.4 mg/mL in 0.01 M
      Tris-HCl buffer, pH 9) activity. Samples (5 mL) were illuminated for 1, 2, 4, 8,
      and 16 s at 3 distances 6, 8.5, and 11 cm from the PUV lamp's quartz window. The
      temperature of 33.5 +/- 1.8 degrees C was observed for the highest treatment time
      of 16 s at the shortest distance of 6 cm, and resulted in a 3.5 log reduction
      (99.95%) in initial LOX activity. Illumination time and distance from the lamp
      significantly (P <= 0.05) affected LOX inactivation. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) was performed on treated LOX
      samples and further protein profile for treated LOX filtrate (<=10 kDa), was
      analyzed by reverse phase high-performance liquid chromatography (RP-HPLC). The
      protein profile analysis revealed that LOX protein degradation was influenced
      significantly (P <= 0.05) by PUV illumination time. 

PMID- 24460767
TI  - Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels
      into the ventral tegmental area increases the rewarding effects of ethanol in
      UChB drinking rats.
AB  - BACKGROUND: A number of studies have shown that ethanol (EtOH) activates dopamine
      neurocircuitries and is self-administered into the ventral tegmental area (VTA)
      of the rat brain. In vitro and in silico studies have showed that
      hyperpolarization-activated cyclic nucleotide-gated (HCN) ionic channels on VTA
      dopamine neurons may constitute a molecular target of EtOH; however, there is no
      in vivo evidence supporting this assumption. METHODS: Wistar-derived University
      of Chile Drinking (UChB) rats were microinjected into the VTA with a lentiviral
      vector coding for rat HCN-2 ionic channel or a control vector. Four days after
      vector administration, daily voluntary EtOH intake was assessed for 30 days under
      a free-access paradigm to 5% EtOH and water. After EtOH consumption studies, the
      effect of HCN-2 overexpression was also assessed on EtOH-induced conditioned
      place preference (CPP); EtOH-induced locomotion, and EtOH-induced dopamine
      release in the nucleus accumbens (NAcc). RESULTS: Rats microinjected with the HCN
      2 coding vector into the VTA showed (i) a ~2-fold increase in their voluntary
      EtOH intake compared to control animals, (ii) lentiviral-HCN-2-treated animals
      also showed an increased CPP to EtOH (~3-fold), (iii) a significant higher
      locomotor activity (~2-fold), and (iv) increased dopamine release in NAcc upon
      systemic administration of EtOH (~2-fold). CONCLUSIONS: Overexpression of HCN-2
      ionic channel in the VTA of rats results in an increase in voluntary EtOH intake,
      EtOH-induced CPP, locomotor activity, and dopamine release in NAcc, suggesting
      that HCN levels in the VTA are relevant for the rewarding properties of EtOH.

PMID- 24460770
TI  - Effect of salts of organic acids on Listeria monocytogenes, shelf life, meat
      quality, and consumer acceptability of beef frankfurters.
AB  - The objective of this study was to evaluate anti-listerial efficacy of salts of
      organic acids, and their impact on the quality of frankfurters. Beef frankfurters
      were manufactured by incorporating organic acids in 5 different combinations: (1)
      control (no marinade addition; C); (2) sodium lactate (2% wt/wt; SL); (3)
      potassium lactate (2% wt/wt; PL); (4) sodium citrate (0.75% wt/wt; SC); and (5)
      sodium lactate (2% wt/wt)/sodium diacetate (0.25% wt/wt; SL/SD). Cooked
      frankfurters were inoculated with streptomycin-resistant (1500 MUg/mL) L.
      monocytogenes (7 log10 CFU/frank). Inoculated and noninoculated frankfurters were
      vacuum packaged and stored at 4  degrees C. Samples were taken weekly up to 10 wk
      for estimation of L. monocytogenes as well as aerobic plate count (APC) and
      psychrotrophs (PSY), respectively. Total of 2 independent trials of the entire
      experiment were conducted. Noninoculated beef frankfurters were evaluated weekly
      by untrained sensory panelists for 7 wk. SL, PL, and SC treatments did not (P >
      0.05) adversely affect consumer acceptability through 8 wk although, SL/SD
      treatment was significantly (P <= 0.05) less preferred across all sensory
      attributes. SL/SD treatment negatively affected product quality, but was able to
      control APC, PSY, and L. monocytogenes levels. SC performed similar to the
      control throughout the 8, 9, and 10 wk storage periods, providing no benefit for
      inhibiting L. monocytogenes (increasing from 7 logs CFU/frank to 10 logs
      CFU/frank throughout storage) or extending shelf life of the beef frankfurters.
      In conclusion, 2% SL and PL, and 2% SL/0.25% SD may be effective L. monocytogenes
      inhibitors (maintaining inoculation levels of 7 logs CFU/frank during storage),
      but changes in SL/SD treatment formulation should be studied to improve product
      quality.

PMID- 24460771
TI  - Apple, carrot, and hibiscus edible films containing the plant antimicrobials
      carvacrol and cinnamaldehyde inactivate Salmonella Newport on organic leafy
      greens in sealed plastic bags.
AB  - The objective of this study was to investigate the antimicrobial effects of
      carvacrol and cinnamaldehyde incorporated into apple, carrot, and hibiscus-based
      edible films against Salmonella Newport in bagged organic leafy greens. The leafy
      greens tested included organic Romaine and Iceberg lettuce, and mature and baby
      spinach. Each leafy green sample was washed, dip inoculated with S. Newport (107
      CFU/mL), and dried. Each sample was put into a Ziploc(r) bag. Edible films pieces
      were put into the Ziploc bag and mixed well. The bags were sealed and stored at 4
      degrees C. Samples were taken at days 0, 3, and 7 for enumeration of survivors.
      On all leafy greens, 3% carvacrol films showed the best bactericidal effects
      against Salmonella. All 3 types of 3% carvacrol films reduced the Salmonella
      population by 5 log10 CFU/g at day 0 and 1.5% carvacrol films reduced Salmonella
      by 1 to 4 log10 CFU/g at day 7. The films with 3% cinnamaldehyde showed 0.5 to 3
      log reductions on different leafy greens at day 7. The films with 0.5% and 1.5%
      cinnamaldehyde and 0.5% carvacrol also showed varied reductions on different
      types of leafy greens. Edible films were the most effective against Salmonella on
      Iceberg lettuce. This study demonstrates the potential of edible films
      incorporated with carvacrol and cinnamaldehyde to inactivate S. Newport on
      organic leafy greens.

PMID- 24460772
TI  - Thermomechanical and morphological properties of nanocomposite films from wheat
      gluten matrix and cellulose nanofibrils.
AB  - The aim of this investigation was the optimization of preparing gluten film
      containing cellulose nanofibrils (CNF). An optimization procedure using central
      composite design (CCD) with three factors (CNF, glycerol, and sodium dodecyl
      sulfate (SDS) concentrations) was used in order to investigate the effect of
      these parameters on the mechanical (tensile strength--TS, elongation at break-
      epsilon(b)) and thermal properties of gluten films and to establish a formulation
      to depict the relationship between the mentioned factors and mechanical
      properties. Through regression analysis, it was found that TS and epsilon(b) well
      fitted by quadratic polynomial equations (R2 = 0.99 and 0.98, respectively) and
      the glycerol concentration was the most significant factor influencing them. The
      optimization was based on maximizing TS and epsilon(b). The optimum conditions
      determined using response surface methodology (RSM) were defined as: CNF
      concentration, 11.129 g/100 g, glycerol concentration, 35.440 g/100 g and SDS
      concentration, 6.259 g/100 g. The predicted responses for these film preparation
      conditions were a TS of 3.630 MPa and epsilon(b) of 86.033%. The verification
      experiments were conducted under optimal conditions to compare predicted and
      actual values of dependent variables. This experiment indicated that both
      predicted and actual values (TS of 3.721 MPa and epsilon(b) of 88.935%) almost
      coincide each other and therefore the estimated models were reasonable and of
      high accuracy to predict dependent variables values. The scanning electron
      microscopy (SEM) images showed non-agglomerated and well dispersed CNF in the
      gluten matrix. Differential scanning calorimetry (DSC) results indicated that
      there is not any significant difference (P > 0.05) between the glass transition
      temperature (T(g)) of optimum nanocomposite (-29.12  degrees C) and control film
      (-29.64  degrees C) and their thermogravimetric analysis (TGA) thermograms showed
      similar degradation behavior.

PMID- 24460773
TI  - Low-dose irradiation can be used as a phytosanitary treatment for fresh table
      grapes.
AB  - Grapes (Vitis vinifera var. Sugraone and Vitis labrusca var. Crimson Seedless)
      were treated with 400, 600, and 800 Gy and the effects on physicochemical factors
      were measured alongside sensory testing during 3 wk of storage. Significant
      changes in texture and color with irradiation and age were measured but little
      visual difference was seen between control and irradiated grapes. However, age
      had a greater effect on firmness than irradiation for Sugraone grapes.
      Irradiation did not significantly (P <= 0.05) affect the SSC/TA ratio, which
      increased during storage. The trained panel detected significant changes in the
      berry texture and rachis color but rated sweetness and flavor significantly
      higher (P <= 0.05) for irradiated Sugraone as compared to the control. Consumers
      liked both the untreated and 800 Gy treated Sugraone grapes, but liked the
      untreated grapes more for texture (P <= 0.05). However, there was no difference
      in liking between irradiated (600 Gy or 800 Gy) and control samples of Crimson
      Seedless for any attribute. The results show that there are varietal differences
      in response to irradiation but the overall maintenance in quality of irradiated
      grapes during 3 wk of storage indicates that irradiation can serve as a viable
      phytosanitary treatment. 

PMID- 24460774
TI  - Circulating undercarboxylated osteocalcin and gingival crevicular fluid tumour
      necrosis factor-alpha in children.
AB  - BACKGROUND: Osteocalcin, a protein secreted by osteoblasts during bone formation,
      is negatively associated with adult periodontal disease. Little is known about
      this association in children. AIM: To examine the extent to which plasma
      undercarboxylated osteocalcin (ucOC) is associated with gingival crevicular fluid
      tumour necrosis factor-alpha (GCF TNF-alpha) - a potential marker of gingival
      inflammation - in children. METHODS: We used data from the Quebec Adipose and
      Lifestyle InvesTigation in Youth cohort, an ongoing longitudinal study on the
      natural history of obesity among Caucasian children with a family history of
      obesity in Quebec, Canada. This cross-sectional analysis from the baseline visit
      includes 120 children aged 8-10 years. Plasma ucOC and GCF TNF-alpha levels were
      determined by enzyme-linked immunosorbent assay. Linear regression analyses,
      adjusting for age, gender, family income, sexual maturity stage, daily physical
      activity, obesity, and fasting glucose were conducted, with TNF-alpha level as
      the dependent variable. RESULTS: A 1-ng/ml increase in ucOC was associated with a
      0.96% decrease (95% confidence interval (CI): -1.69, -0.23) in GCF TNF-alpha
      level. CONCLUSION: A negative association between a marker of bone formation and
      a marker of gingival inflammation was observed as early as childhood among
      Caucasian children with a family history of obesity.

PMID- 24460775
TI  - Development and evaluation of a cadaveric training curriculum for low rectal
      cancer surgery in the English LOREC National Development Programme.
AB  - AIM: The National Development Programme for Low Rectal Cancer in England (LOREC)
      was commissioned in response to wide variation in the outcome of patients with
      low rectal cancer. One of the aims of LOREC was to enhance surgical techniques in
      managing low rectal cancer. This study reports on the development and evaluation
      of a novel national technical skills cadaveric training curriculum in
      extralevator abdominoperineal excision. METHOD: Three sites were commissioned for
      the cadaveric workshops, each delivering the same training curriculum. Training
      was undertaken in pairs using a fresh-frozen cadaveric model under the
      supervision of expert mentors. Global assessment score (GAS) forms were developed
      to promote reflective learning. Feedback on the impact of the workshop was
      obtained from a sample of delegates at the end of the course, and also after 3-23
      months via an online questionnaire. RESULTS: Overall 112 consultant colorectal
      surgeons attended one of 15 cadaveric technical skills training workshops.
      Seventy-six per cent of delegates reported easy identification of anatomy in the
      cadaveric model; 67% found tissue planes easy to interpret. Ninety-six per cent
      of delegates felt the workshop would influence their future practice; 96%
      reported increased awareness of important anatomy. Only 2% of delegates wished to
      pursue supplementary formal training from LOREC. CONCLUSION: Fresh-frozen
      cadavers could provide an effective training model for low rectal surgery. A
      structured 1-day cadaveric workshop has facilitated the dissemination of
      technical skills for management of low rectal cancer. Attending the cadaveric
      workshop enhanced delegates' confidence in performing this procedure.

PMID- 24460776
TI  - Shape of glucose curve can be used as a predictor for screening prediabetes in
      obese children.
AB  - AIM: We attempted to classify obese children with glucose abnormalities into
      different categories based on the plasma glucose (PG) at 0, 60, 120 and 180 min
      and extract the metabolic information from the shape of the PG curve. METHODS: We
      recruited 1205 obese children and 325 nonobese children. Their body weight, blood
      pressure, waist and hip circumferences were measured. An oral glucose tolerance
      test (OGTT) was carried out, and glucose, insulin and glucagon levels were
      tested. RESULTS: There were six forms of abnormal glucose tolerance (AGT) curves
      in obese children in addition to normal glucose tolerance (NGT). 58.3% of obese
      children had AGT. BMI, waist circumference, waist-to-hip ratio and systolic blood
      pressure of each obese group were much higher than in nonobese children (p <
      0.05). HOMA-IR increased significantly in obese children with high fasting PG and
      obese children with high fasting and 3-h PG (p < 0.05), and HOMA-beta cell
      increased significantly in obese children with high 1- and 2-h but low 3-h PG (p
      < 0.05). CONCLUSION: Abnormal glucose tolerance was highly prevalent when
      concerning with glucose values at 60 and 180 min. The shape of PG which contains
      a net of metabolic information can be a predictor for screening prediabetes.

PMID- 24460777
TI  - Development of pulmonary and cardiac sarcoidosis during etanercept therapy.

PMID- 24460778
TI  - Severe childhood asthma and allergy to furry animals: refined assessment using
      molecular-based allergy diagnostics.
AB  - BACKGROUND: Allergy to cats and dogs and polysensitization towards these animals
      are associated with severe childhood asthma. Molecular-based allergy diagnostics
      offers new opportunities for improved characterization and has been suggested to
      be particularly useful in patients with polysensitization and/or severe asthma.
      The aim was to use extract- and molecular-based allergy diagnostics to compare
      patterns of IgE sensitization towards aeroallergens in children with problematic
      severe and controlled asthma. METHODS: Children with a positive ImmunoCAP towards
      any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish
      study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n
      = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by
      ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition,
      Asthma Control Test, spirometry and a methacholine challenge were performed.
      RESULTS: Children with severe asthma had lower asthma control (p < 0.001) and
      FEV1 (p = 0.001) and more bronchial hyper-responsiveness (p = 0.008) in spite of
      high doses of inhaled steroids (>=800 MUg budesonide). Children with severe
      asthma displayed higher levels of IgE antibodies towards cat (17 vs. 3.9, p =
      0.027), dog (3.8 vs. 1.2, p = 0.012) and horse (7.4 vs. 0.7, p = 0.014).
      Sensitization towards Can f 2 (22% vs. 0%, p = 0.009) and Equ c 1 (51% vs. 25%, p
      = 0.03) was more common in severe asthma. IgE levels towards Equ c 1 correlated
      with asthma control (r = -0.41, p = 0.04). CONCLUSION: Children with severe
      allergic asthma had higher sIgE levels to cat, dog and horse. Molecular-based
      allergy diagnostics revealed a more complex molecular spreading of allergen
      components in children with the most severe disease.

PMID- 24460779
TI  - Influence of body weight of mice on the susceptibility to okadaic acid, a
      diarrhetic shellfish poisoning toxin.
AB  - The mouse bioassay (MBA) for diarrhetic shellfish poisoning (DSP) toxins has been
      widely used in many countries of the world. However, different body weight ranges
      of mice are designated to be used in the Japanese official method and European
      Union procedure. In this study we investigated whether and to what extent the
      body weights of the mice affect the susceptibility to DSP toxins. A lethal dose
      of okadaic acid, one of the representative DSP toxins, was injected
      intraperitoneally into mice of five different body weight range groups, from 14
      to 24 g. The mice were observed until 24 h after injection. The lethality was
      100% in the 14-15 and 16-17 g groups, 80% in the 19-20 g group, 50% in the 21-22
      g group, and 40% in the 23-24 g group, with significant differences. Survival
      analysis indicated a relationship between body weights of mice and susceptibility
      to okadaic acid. These results would be quite useful not only for the MBA, but
      also to improve understanding of the biological responses to DSP toxins.

PMID- 24460780
TI  - Influence of pain severity on the quality of life in patients with head and neck
      cancer before antineoplastic therapy.
AB  - BACKGROUND: The aim of this study was to assess the severity of pain and its
      impact on the quality of life (QoL) in untreated patients with head and neck
      squamous cell carcinoma (HNSCC). METHODS: A study group of 127 patients with
      HNSCC were interviewed before antineoplastic treatment. The severity of pain was
      measured using the Brief Pain Inventory (BPI) questionnaire, and the QoL was
      assessed with the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and the head and neck
      module (QLQ-H&N35). RESULTS: The mean age of the patients was 57.9 years, and
      there was a predominance of men (87.4%). The most frequent site of the primary
      tumor was the oral cavity (70.6%), and the majority of the patients had advanced
      cancers (stages III and IV). QoL in early stage of cancer obtained better scores.
      Conversely, the patients with advanced stage cancer scored significantly higher
      on the symptom scales regarding fatigue, pain, appetite loss and financial
      difficulties, indicating greater difficulties. Regard to the severity of pain,
      patients with moderate-severe pain revealed a significantly worse score than
      patients without pain. CONCLUSIONS: The severity of pain is statistically related
      to the advanced stages of cancer and directly affects the QoL. An assessment of
      the quality of life and symptoms before therapy can direct attention to the most
      important symptoms, and appropriate interventions can then be directed toward
      improving QoL outcomes and the response to treatment.

PMID- 24460781
TI  - The dependency on central government funding of decentralised health systems:
      experiences of the challenges and coping strategies in the Kongwa District,
      Tanzania.
AB  - BACKGROUND: Decentralised health systems in Tanzania depend largely on funding
      from the central government to run health services. Experience has shown that
      central funding in a decentralised system is not an appropriate approach to
      ensure the effective and efficient performance of local authorities due to
      several limitations. One of the limitations is that funds from the central
      government are not disbursed on a timely basis, which in turn, leads to the
      serious problem of shortage of financial resources for Council Health Management
      Teams (CHMT). This paper examines how dependency on central government funding in
      Tanzania affects health activities in Kongwa district council and the strategies
      used by the CHMT cope with the situation. METHODS: The study adopted a
      qualitative approach and data were collected using semi-structured interviews and
      focus group discussions. One district in the central region of Tanzania was
      strategically selected. Ten key informants involved in the management of health
      service delivery at the district level were interviewed and one focus group
      discussion was held, which consisted of members of the council health management
      team. The data generated were analysed for themes and patterns. RESULTS: The
      results showed that late disbursement of funds interrupts the implementation of
      health activities in the district health system. This situation delays the
      implementation of some activities, while a few activities may not be implemented
      at all. However, based on their prior knowledge of the anticipated delays in
      financial disbursements, the council health management team has adopted three
      main strategies to cope with this situation. These include obtaining supplies and
      other services on credit, borrowing money from other projects in the council, and
      using money generated from cost sharing. CONCLUSION: Local government authorities
      (LGAs) face delays in the disbursement of funds from the central government. This
      has necessitated introduction of informal coping strategies to deal with the
      situation. National-level policy and decision makers should minimise the
      bureaucracy involved in allocating funds to the district health systems to reduce
      delays.

PMID- 24460782
TI  - Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo;
      a clue to interfollicular melanocyte stem cell reservoir.
AB  - There has been a long lasting controversy over whether melanocytes (MCs) in
      vitiligo are actually lost or still present but functionally inactive. We aimed
      to evaluate the MC cell lineage in follicular and interfollicular vitiliginous
      epidermis through immunohistochemical localization of Human Melanoma Black-45
      (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with
      clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies
      from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were
      examined. Differentiated active MCs were detected in 44% of interfollicular
      epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin.
      Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in
      lesional skin. Melanocyte precursors/stem cells of IFE were significantly
      associated with residual melanin pigment (p = 0.007) and with absence of
      angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively
      correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001)
      and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p <
      0.001) was progressively decreasing with advanced histopathologic grading. There
      was no significant association between interfollicular or follicular expression
      of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or
      its duration. In conclusion, functioning MCs may exist in vitiligo. The presence
      of MC precursors/stem cells in IFE may provide an additional reservoir needed for
      repigmentation.

PMID- 24460783
TI  - A novel anterograde neuronal tracing technique to selectively label spinal
      afferent nerve endings that encode noxious and innocuous stimuli in visceral
      organs.
AB  - BACKGROUND: One major weakness in our understanding of pain perception from
      visceral organs is the lack of knowledge of the location, morphology and
      neurochemistry of all the different types of spinal afferent nerve endings, which
      detect noxious and innocuous stimuli. This is because we lack techniques to
      selectively label only spinal afferents. Our aim was to develop an anterograde
      tracing technique that labels only spinal afferent nerve endings in visceral
      organs, without also labeling all other classes of extrinsic afferent and
      efferent nerves. METHODS: Mice were anesthetized with isoflurane and dextran
      biotin injected, via glass micropipettes (diameter 5 MUm), into L6 and S1 dorsal
      root ganglia. Mice recovered for 7 days, were then euthanized and the colon
      removed. KEY RESULTS: Anterograde labeling revealed multiple unique classes of
      afferent endings that terminated within distinct anatomical layers of the colon
      and rectum. We characterized a particular class of intramuscular ending in the
      circular muscle (CM) layer of the colon that consists of multiple varicose axons
      that project circumferentially. CONCLUSIONS & INFERENCES: We demonstrate a
      technique for selective anterograde labeling of spinal afferent nerve endings in
      visceral organs. This approach facilitates selective visualization of the precise
      morphology and location of the different classes of spinal afferent endings,
      without visual interference caused by indiscriminant labeling of other classes of
      afferent and efferent nerve axons which also innervate internal organs. We have
      used this new technique to identify and describe the details of a particular
      class of intramuscular spinal afferent ending in the CM layer of mouse large
      intestine.

PMID- 24460784
TI  - Effect of early long-pulse pulsed dye laser treatment in infantile hemangiomas.
AB  - BACKGROUND: Despite several recent reports on the efficacy of long-pulse pulsed
      dye laser (LP-PDL) in treating infantile hemangiomas, controversy remains.
      OBJECTIVES: To determine the beneficial effects of early therapeutic intervention
      with LP-PDL in superficial and mixed hemangiomas. METHODS AND MATERIALS: Clinical
      data from 40 children with 47 hemangiomas in preproliferative or proliferative
      phase treated with LP-PDL in a Korean tertiary hospital over 5 years were
      analyzed retrospectively. Treatments were repeated at 1- to 4-week intervals
      until growth stopped. RESULTS: Of the 47 hemangiomas, 32 were superficial, and 15
      were mixed at presentation. Age was 9.6 +/- 5.9 weeks at initiation of treatment
      and 18.0 +/- 8.6 weeks at completion, and a positive linear correlation existed
      between the two. There were a mean of 4.6 +/- 2.6 treatments per hemangioma,
      which was lower in superficial than in mixed hemangiomas. Improvement in color
      was documented in 84.4% of superficial and 86.7% of mixed hemangiomas, and 75.0%
      of superficial and 66.7% of mixed shrank. Hyperpigmentation occurred in two
      superficial hemangiomas. CONCLUSION: Early intervention in hemangiomas using LP
      PDL successfully prevents further growth and accelerates a transition to plateau
      or involution phase with minimal adverse events, achieving good cosmetic
      outcomes.

PMID- 24460785
TI  - Long-term effect of an educational intervention regarding dental trauma first
      aid: a phase II study.
AB  - AIM: Interventions that improve knowledge about emergency management of traumatic
      dental injuries may be a good way to achieve a more favorable prognosis in such
      situations. We set out to evaluate the short- and long-term effects of combined
      educational interventions on health teachers, including lecture presentation,
      question-and-answer sessions, and informational posters to promote awareness
      regarding emergency measures for traumatized teeth. Assessment was performed
      using a three-part questionnaire, including demographic data, knowledge, and self
      assessment. Using a census sampling method, 52 health teachers of 68 potential
      candidates participated in the study. The questionnaires of 38 teachers who
      participated at all three intervals, including before (T0), immediately after
      (T1), and 36 months after (T2) the intervention, were analyzed. Statistical
      analysis involved Cochrane and McNemar's tests. Totally, results revealed an
      increase in knowledge from T0 to T1 and T2 intervals (P < 0.017). This study
      shows the positive effect of educational campaigns and, therefore, serves to
      encourage professionals to embark on innovative educational programs in this
      field.

PMID- 24460786
TI  - Residual neuromuscular blockade and postoperative critical respiratory events:
      literature review.
AB  - AIMS AND OBJECTIVES: To investigate and synthesise published literature on the
      associations between residual neuromuscular blockade and critical respiratory
      events of postoperative adult patients in the postanaesthesia care unit.
      BACKGROUND: Residual neuromuscular blockade continues to be common among patients
      transferred to the postanaesthesia care unit after general anaesthesia, while
      negative effects of residual neuromuscular blockade on respiratory function have
      been demonstrated in laboratory volunteers. DESIGN: Literature review. METHODS:
      Using key terms, a search was conducted in Cumulative Index for Nursing and
      Allied Health Literature, PubMed, Web of Science, Cochrane Database and EMBASE
      (January 1990-May 2013) for clinical trials or observational studies on the
      associations between residual neuromuscular blockade and critical respiratory
      events, published in English-language journals. RESULTS: Nine articles met the
      inclusion criteria. Residual neuromuscular blockade definition threshold differed
      between studies. Among critical respiratory events, only hypoxaemia was
      investigated in all included studies. Residual neuromuscular blockade was
      significantly associated with increased incidence of hypoxaemia during
      postanaesthesia care unit stay in most studies, while associations with the rest
      of the critical respiratory events were inconclusive. CONCLUSIONS: Although
      limited, existing research has provided evidence that patients with residual
      neuromuscular blockade are at high risk of early postoperative hypoxaemia.
      Further studies are needed to investigate independent associations between
      residual neuromuscular blockade and critical respiratory events, along with
      causality of these associations. The clinical importance of residual
      neuromuscular blockade for groups at high risk of critical respiratory events
      should also be investigated. RELEVANCE TO CLINICAL PRACTICE: Healthcare
      professionals have to be aware of the increased risk of hypoxaemia in patients
      with residual neuromuscular blockade. Efforts to decrease residual neuromuscular
      blockade incidence, combined with identification and appropriate evaluation of
      patients with residual neuromuscular blockade during postanaesthesia care unit
      stay, are recommended.

PMID- 24460788
TI  - Depression as a mediator of negative cognitive style and hopelessness in stress
      generation.
AB  - Over the past 20 years, there has been considerable interest in the role of
      cognitive factors in the stress generation process. Generally, these studies find
      that depressed individuals, or individuals at cognitive risk for depression, are
      more likely to experience stressful life events that are in part influenced by
      their own characteristics and behaviours (i.e., negative dependent events).
      However, there is still much to be learnt about the mediators of these effects.
      For example, does the development of depression symptoms explain why individuals
      at cognitive risk for depression experience increased negative dependent events?
      Or, is it that increases in cognitive risk explain why depressed individuals
      experience increased negative dependent events? To explore these questions, a
      short-term prospective study was conducted with 209 college students who were
      given measures of depression, depressogenic risk factors (i.e., negative
      cognitive style and hopelessness), and negative dependent events at two time
      points 6 weeks apart. Support was found for three models: (1) depression symptoms
      mediated the relationship between negative cognitive style and negative dependent
      events; (2) depression symptoms mediated the relationship between hopelessness
      and negative dependent events; and (3) first hopelessness and then depression
      symptoms mediated the relationship between negative cognitive style and negative
      dependent events in a multiple-step model. In contrast, the reverse models were
      not confirmed, suggesting specificity in the direction of the mediational
      sequence.

PMID- 24460787
TI  - Suppression of NAD(P)H-quinone oxidoreductase 1 enhanced the susceptibility of
      cholangiocarcinoma cells to chemotherapeutic agents.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) is highly resistant to most of the known
      chemotherapeutic treatments. NAD(P)H-quinone oxidoreductase 1 (NQO1) is an
      antioxidant/detoxifying enzyme recently recognized as an important contributor to
      chemoresistance in some human cancers. However, the contribution of NQO1 to
      chemotherapy resistance in CCA is unknown. METHODS: Two CCA cell lines, KKU-100
      and KKU-M214, with high and low NQO1 expression levels, respectively, were used
      to evaluate the sensitivity to chemotherapeutic agents; 5-fluorouracil (5-FU),
      doxorubicin (Doxo), and gemcitabine (Gem). NQO1 and/or p53 expression in KKU-100
      cells were knocked down by siRNA. NQO1 was over-expressed in KKU-M214 cells by
      transfection with pCMV6-XL5-NQO1 expression vector. CCA cells with modulated NQO1
      and/or p53 expression were treated with chemotherapeutic agents, and the
      cytotoxicity was assessed by SRB assay. The mechanism of enhanced
      chemosensitivity was evaluated by Western blot analysis. RESULTS: When NQO1 was
      knocked down, KKU-100 cells became more susceptible to all chemotherapeutic
      agents. Conversely, with over-expression of NQO1 made KKU-M214 cells more
      resistant to chemotherapeutic agents. Western blot analysis suggested that
      enhanced chemosensitivity was probably due to the activation of p53-mediated cell
      death. Enhanced susceptibility to chemotherapeutic agents by NQO1 silencing was
      abolished by knockdown of p53. CONCLUSIONS: These results suggest that inhibition
      of NQO1 could enhance the susceptibility of CCA to an array of chemotherapeutic
      agents.

PMID- 24460789
TI  - Assessment of the nursing skill mix in Mozambique using a task analysis
      methodology.
AB  - BACKGROUND: The density of the nursing and maternal child health nursing
      workforce in Mozambique (0.32/1000) is well below the WHO minimum standard of 1
      nurse per 1000. Two levels of education were being offered for both nurses and
      maternal child health nurses, in programmes ranging from 18 to 30 months in
      length. The health care workforce in Mozambique also includes Medical Technicians
      and Medical Agents, who are also educated at either basic or mid-level. The
      Ministry of Health determined the need to document the tasks that each of the six
      cadres was performing within various health facilities to identify gaps, and
      duplications, in order to identify strategies for streamlining workforce
      production, while retaining highest educational and competency standards. The
      methodology of task analysis (TA) was used to achieve this objective. This
      article provides information about the TA methodology, and selected outcomes of
      the very broad study. METHODS: A cross-sectional descriptive task analysis survey
      was conducted over a 15 month period (2008-2009). A stratified sample of 1295
      individuals was recruited from every type of health facility in all of
      Mozambique's 10 provinces and in Maputo City. Respondents indicated how
      frequently they performed any of 233 patient care tasks. Data analysis focused on
      identifying areas where identical tasks were performed by the various cadres.
      Analyses addressed frequency of performance, grouped by level of educational
      preparation, within various types of health facilities. RESULTS: Task sharing
      ranged from 74% to 88% between basic and general nurse cadres and from 54% to 88%
      between maternal and child health nurse cadres, within various health facility
      types. Conversely, there was distinction between scope of practice for nursing
      and maternal/child health nursing cadres. CONCLUSION: The educational pathways to
      general nursing and maternal/child health nursing careers were consolidated into
      one 24 month programme for each career. The scopes of practice were affirmed
      based on task analysis survey data.

PMID- 24460790
TI  - Long-term risk of sepsis among survivors of acute kidney injury.
AB  - Many prior studies have shown that, in critically ill patients, acute kidney
      injury (AKI) commonly occurs in association with sepsis and its presence portends
      an increased likelihood of poor outcomes. In contrast, few studies have focused
      specifically on the influence of AKI on the long-term risk of developing sepsis.
      In a previous issue of Critical Care, a population-based cohort study by Lai and
      colleagues reported a long-term increased risk of severe sepsis for patients
      surviving beyond 90 days following hospitalization with an episode of AKI
      requiring renal replacement therapy. While the pathophysiologic mechanisms that
      underpin this finding remain to be elucidated and causality cannot be proven,
      this study suggests that severe AKI confers long-term susceptibility to infection
      and focuses further attention on the critical importance of long-term
      surveillance for survivors of severe AKI. Further mechanistic and clinical
      studies are required to more precisely define the extent and duration of any
      increased risk of severe sepsis beyond which a need for ongoing renal replacement
      therapy following AKI might be associated. Nonetheless, this novel study by Lai
      and colleagues could lead to a number of important new avenues for clinical
      inquiry, such as whether it might be possible to identify those most susceptible
      to severe sepsis after AKI and, ultimately, whether such episodes might be
      preventable. 

PMID- 24460791
TI  - EBNA1 binding and epigenetic regulation of gastrokine tumor suppressor genes in
      gastric carcinoma cells.
AB  - BACKGROUND: Epstein-Barr Virus (EBV) latently infects ~10% of gastric carcinomas
      (GC). Epstein-Barr Nuclear Antigen 1 (EBNA1) is expressed in EBV-associated GC,
      and can bind host DNA, where it may impact cellular gene regulation. Here, we
      show that EBNA1 binds directly to DNA upstream of the divergently transcribed GC
      specific tumor suppressor genes gastrokine 1 (GKN1) and gastrokine 2 (GKN2).
      METHODS: We use ChIP-Seq, ChIP-qPCR, and EMSA to demonstrate that EBNA1 binds
      directly to the GKN1 and GKN2 promoter locus. We generate AGS-EBV, and AGS-EBNA1
      cell lines to study the effects of EBNA1 on GKN1 and GKN2 mRNA expression with or
      without 5' azacytidine treatment. RESULTS: We show that gastrokine genes are
      transcriptionally silenced by DNA methylation. We also show that latent EBV
      infection further reduces GKN1 and GKN2 expression in AGS gastric carcinoma
      cells, and that siRNA depletion of EBNA1 partially alleviates this repression.
      However, ectopic expression of EBNA1 slightly increased GKN1 and GKN2 basal mRNA
      levels, but reduced their responsiveness to demethylating agent. CONCLUSIONS:
      These findings demonstrate that EBNA1 binds to the divergent promoter of the GKN1
      and GKN2 genes in GC cells, and suggest that EBNA1 contributes to the complex
      transcriptional and epigenetic deregulation of the GKN1 and GKN2 tumor suppressor
      genes in EBV positive GC.

PMID- 24460792
TI  - Curcumin attenuates staphylococcus aureus-induced acute lung injury.
AB  - INTRODUCTION: Curcumin has remarkable anti-inflammatory and antioxidant
      properties. However, its effects on bacterium-induced acute lung injury (ALI) are
      not fully understood. OBJECTIVE: To investigate the protective effects of
      curcumin on a mouse model of S. aureus-induced ALI. METHODS: Mice were pretreated
      with intraperitoneal injection of curcumin or vehicle 2 h before Staphylococcus
      aureus instillation. The survival rate and bacterial burden after infection were
      recorded. Mice were sacrificed for the analyses of severity of pneumonia,
      integrity of lung barrier, disorder of coagulation cascades and extent of
      inflammation 12 h postinfection. The production of proinflammatory cytokines and
      chemokines in the lung and bronchoalveolar lavage fluid was detected. RESULTS:
      Pretreatment with curcumin markedly attenuated S. aureus-induced pneumonia,
      barrier disruption, lung edema and vascular leakage. Activation of plasminogen
      activator inhibitor-1 and infiltration of neutrophils were reduced by curcumin,
      together with lower levels of proinflammatory cytokines and chemokines.
      CONCLUSION: Curcumin can alleviate S. aureus-induced ALI through multiple
      pathways.

PMID- 24460793
TI  - 8p23 beta-defensin copy number determination by single-locus pseudogene-based
      paralog ratio tests risk bias due to low-frequency sequence variations.
AB  - BACKGROUND: The copy number variation (CNV) in beta-defensin genes (DEFB) on
      human chromosome 8p23 has been proposed to contribute to the phenotypic
      differences in inflammatory diseases. However, determination of exact DEFB CN is
      a major challenge in association studies. Quantitative real-time PCR (qPCR),
      paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification
      (MLPA) have been extensively used to determine DEFB CN in different laboratories,
      but inter-method inconsistencies were observed frequently. In this study we asked
      which one is superior among the three methods for DEFB CN determination. RESULTS:
      We developed a clustering approach for MLPA and PRT to statistically correlate
      data from a single experiment. Then we compared qPCR, a newly designed PRT and
      MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best
      convergence and clustering results of the raw data and the highest call rate. In
      addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%,
      respectively) were unacceptably low with underestimated CN by qPCR. Concordance
      rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated
      CN by one in a subset of samples. In these samples a sequence variant which
      caused complete PCR dropout of the respective DEFB cluster copies was found in
      one primer binding site of one of the targeted paralogous pseudogenes.
      CONCLUSION: MLPA is superior to PRT and even more to qPCR for DEFB CN
      determination. Although the applied PRT provides in most cases reliable results,
      such a test is particularly sensitive to low-frequency sequence variations
      preferably accumulating in loci like pseudogenes which are most likely not under
      selective pressure. In the light of the superior performance of multiplex assays,
      the drawbacks of such single PRTs could be overcome by combining more test
      markers.

PMID- 24460795
TI  - The effect of the thermal diode laser (wavelength 808-980 nm) in non-surgical
      periodontal therapy: a systematic review and meta-analysis.
AB  - FOCUSED QUESTION: What is the adjunctive effect of a diode laser (DL) following
      non-surgical periodontal debridement (SRP) during the initial phase of
      periodontal therapy on the clinical parameters of periodontal inflammation.
      MATERIAL AND METHODS: The MEDLINE-PubMed, Cochrane-Central Register of Controlled
      Trials and EMBASE databases were searched up to September 2013. Probing pocket
      depth (PPD) and clinical attachment loss (CAL) were selected as outcome
      variables. Also plaque scores (PS), bleeding scores (BS) and the Gingival Index
      (GI) were considered outcome measures. Data were extracted and a meta-analysis
      (MA) was performed where appropriate. RESULTS: Independent screening of 416
      unique papers resulted in nine eligible publications. The MA evaluating PPD, CAL
      and PS showed no significant effect. The only significance favouring adjunctive
      use of the DL was observed for the outcome parameters GI and BS. CONCLUSION: The
      collective evidence regarding adjunctive use of the DL with SRP indicates that
      the combined treatment provides an effect comparable to that of SRP alone. That
      is for PPD and CAL. The body of evidence considering the adjunctive use of the DL
      is judged to be "moderate" for changes in PPD and CAL. With respect to BS, the
      results showed a small but significant effect favouring the DL, however, the
      clinical relevance of this difference remains a question. This systematic review
      questions the adjunctive use of DL with traditional mechanical modalities of
      periodontal therapy in patients with periodontitis.

PMID- 24460794
TI  - An immune response study of oakmoss absolute and its constituents atranol and
      chloroatranol.
AB  - BACKGROUND: Atranol and chloroatranol are the main allergens of oakmoss absolute.
      However, the immune responses induced by these substances are poorly
      characterized. OBJECTIVES: To characterize immune responses induced by atranol,
      chloroatranol and oakmoss absolute in mice. METHODS: Mice were sensitized and
      challenged with various concentrations of atranol, chloroatranol, and oakmoss
      absolute. The immune responses were analysed as B cell infiltration, T cell
      proliferation in the draining lymph nodes, and expression of interleukin (IL)-18,
      IL-1beta and tumour necrosis factor-alpha in skin. The cytotoxicity of atranol
      and chloroatranol against keratinocytes was determined. RESULTS: Sensitization
      experiments showed that atranol, chloroatranol and oakmoss induced sensitization
      when applied in high concentrations. Challenge experiments showed that even low
      concentrations of atranol and chloroatranol induced sensitization. In parallel,
      atranol and chloroatranol elicited challenge reactions following sensitization
      with oakmoss. The magnitude of the immune response to the three allergens
      increased in the following order: atranol, chloroatranol, and oakmoss. The
      expression of proinflammatory cytokines was induced by chloroatranol and oakmoss,
      but not by atranol. Chloroatranol was found to be more cytotoxic than atranol
      against keratinocytes. CONCLUSIONS: Atranol and chloroatranol can elicit both
      sensitization and challenge reactions, but the mixture of allergens in oakmoss
      absolute is more potent than atranol and chloroatranol alone.

PMID- 24460796
TI  - Differences in risk of injury in the U.S. general population by injury treatment
      type: data from the 1995 to 2010 national alcohol surveys.
AB  - BACKGROUND: While emergency room (ER) studies have documented a strong
      association of alcohol with injury, these studies are not necessarily
      representative of the general population. To evaluate comparative risk of injury
      from drinking for those treated in the ER with non-ER-treated injuries (those
      treated elsewhere or those not treated), data on alcohol and injury are analyzed
      in the U.S. general population by type of injury treatment. METHODS: Relative
      risk (RR) of injury from drinking within 6 hours prior to the event was analyzed
      using case-crossover analysis based on respondents' usual frequency of drinking
      in 4 (1995 to 2010) National Alcohol Surveys (n = 4,819). RESULTS: RR was 1.01
      for the total injured and significantly elevated for ER-treated injured (1.46),
      but not for those treated elsewhere (0.75) and those not treated (1.02). RR was
      significantly elevated for those aged 18 to 30 years (1.45; 1.14, 1.85), Blacks
      (1.54; 1.11, 2.14) and Hispanics (1.98; 1.51, 2.59), those positive on the Rapid
      Alcohol Problems Screen (RAPS4) as a measure of alcohol dependence (2.41; 1.86,
      3.11), and for motor vehicle injuries (2.61; 1.49, 4.58) or cutting/piercing
      injuries (2.04, 1.10, 3.81). For those reporting ER-treated injuries, significant
      effect modification was found for those aged 18 to 30 years (RR = 2.29), Blacks
      (RR = 2.59) and Hispanics (RR = 2.68), high risk-taking (RR = 1.71), positive
      RAPS4 (RR = 3.69), and for motor vehicle (RR = 3.79) and cutting/piercing
      injuries (RR = 2.60). CONCLUSIONS: Data suggest alcohol plays a larger role in
      injuries for which ER treatment is sought than for other injuries, and estimates
      for injury from drinking derived from ER studies may be elevated. Future general
      population studies should take into account intensity of exposure to alcohol
      prior to injury, potential recall bias (by eliciting data on the proximity of
      injury to time of the respondent interview) and severity of injury, for improving
      estimates of the attributable burden of alcohol to injury in society.

PMID- 24460797
TI  - Switch from tenofovir to raltegravir increases low bone mineral density and
      decreases markers of bone turnover over 48 weeks.
AB  - BACKGROUND: Tenofovir, particularly when given with a ritonavir-boosted protease
      inhibitor (rPI), reduces bone mineral density (BMD) and increases bone turnover
      markers (BTMs), both of which are associated with increased fracture risk.
      Raltegravir has not been associated with bone loss. METHODS: In an open-label,
      nonrandomized, pilot study, tenofovir was switched to raltegravir in adults also
      receiving a rPI for at least 6 months with a spine or hip T-score <= -1.0 and
      plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 3 months. The primary
      endpoint was BMD change by dual-energy X-ray absorptiometry. Student's paired t
      test was used to compare continuous variables. Factors associated with BMD
      increase were assessed using linear regression. RESULTS: Thirty-seven patients
      were enrolled in the study: 97% were male, the mean age was 49 years, the mean T
      scores were -1.4 (spine) and -1.3 (total left hip), and the mean tenofovir
      treatment duration was 3.1 years. BMD increases were significant at weeks 24 and
      48. At week 48, spine BMD increased by 3.0% [95% confidence interval (CI) 1.9,
      4.0%; P < 0.0001] and left total hip BMD increased by 2.5% (95% CI 1.6, 3.3%; P <
      0.0001). BTMs (N-telopeptide, osteocalcin and bone alkaline phosphatase) all
      decreased significantly at week 24 (P <= 0.0017). There were no raltegravir
      related serious or grade 3-4 adverse events. HIV viral load remained <50
      copies/mL plasma on raltegravir/rPI therapy. CONCLUSIONS: Switching virologically
      suppressed HIV-infected adults with low BMD taking an rPI from tenofovir to
      raltegravir was safe and significantly improved hip and spine BMD and reduced
      markers of bone turnover over 48 weeks.

PMID- 24460798
TI  - A case series of autoimmune diseases accompanied by incidentally diagnosed
      monoclonal gammopathy: is there a link between the two diseases?
AB  - AIM: Although the etiology of plasma cell dyscrasia is poorly understood, there
      is evidence for immune dysregulation or sustained immune stimulation playing a
      pivotal role in the pathogenesis of these diseases, including chronic infection
      and autoimmune disorders. In this study, we report four autoimmune disease cases
      where monoclonal gammopathy (MG) was incidentally found during follow-up.
      METHODS: We retrospectively reviewed the medical charts and laboratory test
      results in the following four cases: neuromyelitis optica, Kikuchi disease,
      Sjogren syndrome and ankylosing spondylosis. RESULTS: The four patients were
      older than 55 years and the male-to-female ratio was 2 : 2. The autoimmune
      disease in each case developed differently because two patients had coincidental
      detection of MG, whereas MG was detected 2 years and 10 years after diagnosis in
      the other two patients. The amount of M-components in the blood for two cases was
      <= 1 g/dL. For the other two subjects, M-components were >= 3 g/dL. CONCLUSION: A
      high prevalence of MG of undetermined significance (MGUS) has been noted in a
      series of patients with immune disorders, suggesting a possible association with
      MG. Further studies should focus on determining how MG relates to various
      clinical information and laboratory parameters, such as disease duration, disease
      activity and higher sedimentation rate. In the future, we also need to identify
      which stimuli, such as cytokine types and levels, can induce lymphocyte clonal
      transformation and the production of monoclonal antibodies.

PMID- 24460799
TI  - Baseline adjustment and change revisited: effect of smoking on change in
      periodontal status following periodontal therapy.
AB  - Smokers have frequently been reported to have more severe periodontitis, to
      respond less favorably to periodontal therapy, and to show elevated rate of
      recurrence compared with non-smokers. The aims of this study was to compare the
      results of baseline-adjusted and -unadjusted analyses when assessing the effect
      of smoking on change in periodontal status following therapy and to discuss the
      methodological issues involved. This is a secondary analysis of data from 180
      periodontitis patients enrolled in a randomized controlled clinical intervention
      trial. Information on smoking habits was elicited from the participants before,
      and 12 months after, therapy. The clinical parameters analyzed were probing
      pocket depth and clinical attachment level, using both simple analysis of change
      (SAC) and analysis of covariance (ancova), adjusting for age, gender, and
      treatment group. The current smokers presented with more severe periodontitis at
      baseline than did former and never smokers. Results of the SAC indicated that the
      current smokers benefitted more from treatment than did former or never smokers,
      whereas the results of the baseline-adjusted ancova indicated no such
      differences. Both sets of results are likely to be biased with respect to valid
      conclusions regarding the 'causal' effect of smoking. Possible sources of bias
      are discussed.

PMID- 24460802
TI  - Surface morphology of superficial cells in irradiated oral mucosa: an
      experimental study in beagle dog.
AB  - OBJECTIVES: The aim of the present study is to investigate if radiation induces
      changes in the superficial cells of the oral mucosa and secondly to describe
      morphological characteristics of the cell surface structure by scanning electron
      microscopy (SEM). MATERIALS AND METHODS: Ten beagle dogs aged 1-2 years were used
      in this study. One side of each mandible was irradiated in two sessions, each
      lasting 1 week. The total dosage was 40 Gy (Group A; 5 dogs) and 50 Gy (Group B;
      5 dogs), in five fractions of 4 Gy. The other side of mandible (non-irradiated)
      served as a control. The specimen was harvested with a scalpel from the alveolar
      mucosa of the irradiated area 1 year after irradiation and studied with SEM.
      RESULTS: In the control side, the surface structure of the cell contains straight
      parallel or branched microplicae (MPL), which were equally spaced over the cell
      surfaces. Discontinuous and short MPL were typical cell structure of irradiated
      mucosa. In 50 Gy group, the surface structure of epithelial cell was pitted and
      the cell boundaries were thick. CONCLUSIONS: The novelty of the present study is
      that radiation disrupts superficial cells of the oral mucosa. The role of the MPL
      structure of the superficial cells in mucositis development is discussed.

PMID- 24460800
TI  - Residual macrovascular risk in 2013: what have we learned?
AB  - Cardiovascular disease poses a major challenge for the 21st century, exacerbated
      by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best
      standards of care, including high-dose statins, can ameliorate the risk of
      vascular complications, patients remain at high risk of cardiovascular events.
      The Residual Risk Reduction Initiative (R3i) has previously highlighted
      atherogenic dyslipidaemia, defined as the imbalance between proatherogenic
      triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic
      apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an
      important modifiable contributor to lipid-related residual cardiovascular risk,
      especially in insulin-resistant conditions. As part of its mission to improve
      awareness and clinical management of atherogenic dyslipidaemia, the R3i has
      identified three key priorities for action: i) to improve recognition of
      atherogenic dyslipidaemia in patients at high cardiometabolic risk with or
      without diabetes; ii) to improve implementation and adherence to guideline-based
      therapies; and iii) to improve therapeutic strategies for managing atherogenic
      dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a
      simple, practical tool for treatment decisions regarding the management of lipid
      related residual cardiovascular risk. Addition of a fibrate, niacin (North and
      South America), omega-3 fatty acids or ezetimibe are all options for combination
      with a statin to further reduce non-HDL cholesterol, although lacking in hard
      evidence for cardiovascular outcome benefits. Several emerging treatments may
      offer promise. These include the next generation peroxisome proliferator
      activated receptoralpha agonists, cholesteryl ester transfer protein inhibitors
      and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin
      type 9. However, long-term outcomes and safety data are clearly needed. In
      conclusion, the R3i believes that ongoing trials with these novel treatments may
      help to define the optimal management of atherogenic dyslipidaemia to reduce the
      clinical and socioeconomic burden of residual cardiovascular risk. 

PMID- 24460803
TI  - Acrylamide, 5-hydroxymethylfurfural and N(epsilon)-carboxymethyl-lysine in coffee
      substitutes and instant coffees.
AB  - Sensitive analytical methods were developed and validated for the quantification
      of acrylamide, N(epsilon)-carboxymethyl-lysine (CML) and 5-hydroxymethylfurfural
      (HMF) in 24 commercial coffee substitutes (CSs) and 12 instant coffees (ICs).
      Acrylamide levels varied widely from 200 to 4940 ug kg(-1) with higher levels in
      CSs. Only two out of 24 CSs had a level of acrylamide above the indicative value
      set for this food category by the European Commission (4000 ug kg(-1)). None of
      the ICs tested in this study exceeded the indicative value set for this foodstuff
      (900 ug kg(-1)). CML ranged from 0.17 to 47 mg kg(-1) and it increased in
      proportion to the protein content of the samples. The highest concentrations were
      found in IC partly due to the relatively high protein content of this food group.
      HMF was the most abundant neoformed compound (NFC) found in the tested commercial
      samples. It was found between 0.59 and 13 g kg(-1). Among other food categories
      IC and CS could appear to be major contributors to the exposure to NFCs if
      consumed on a daily basis. Further investigations are needed to elucidate the
      acrylamide formation during processing and to determine the daily intake level of
      frequent consumers of these products.

PMID- 24460804
TI  - Electrocardiographic reference values for a population of older adults in sub
      Saharan Africa.
AB  - BACKGROUND/OBJECTIVES: Older adults in sub-Saharan Africa (SSA) are at greatest
      risk of an impending noncommunicable diseases epidemic, of which cardiac disease
      is the most prevalent contributor. Thus, it is essential to establish
      electrocardiographic reference values for a population that is likely to differ
      genetically and environmentally from others where reference values are
      established. METHODS: Two thousand two hundred thirty-two apparently healthy
      community-based participants without known cardiac disease aged 70+ in rural
      Tanzania underwent 12-lead electrocardiography. Electrocardiograms were digitally
      analyzed and gender-specific reference values for P duration (PD), P amplitude
      (PAMP), P area (PAREA), P terminal negative force (V1) (PTNF), PR interval, QRS
      duration (QRSD), QT/QTc, R amplitude (II, V5) (RAMP) LVH index (LVHI), R axis and
      R/S ratio (V1) reported, following univariate analysis of covariance using a
      multiple linear regression model, adjusting for age, systolic blood pressure
      (SBP), body mass index (BMI), and RR interval. RESULTS: Data from 1824 subjects
      were suitable for analysis. Adjusted mean values for men/women were: PD 115/110
      ms, PAMP (avg) 123/114 MUV, PAMP (II) 203/190 MUV, PAREA (avg) 5.3/4.6 mV*s,
      PAREA (II) 9.3/8.1 mV*s, PTNF 1.7/1.4 mV*s, PR 158/152 ms, QRSD 89/84 ms, QT
      370/375 ms, QTc 421/427 ms, RAMP (II) 805/854 MUV, (V5) 2022/1742 MUV, LVHI
      3.0/2.8 mV (Sokolow-Lyon), 1.293/1.146 mV (Cornell), R axis 51/49 degrees , R/S
      0.2/0.2. Excluding PTNF , R axis and R/S ratio, all gender differences were
      significant (P < 0.001 apart from LVHI [Sokolow-Lyon; P < 0.005)] and RAMP (II)
      [P < 0.05]) following adjustment for age, SBP, BMI, and RR interval. CONCLUSIONS:
      Our description of comprehensive electrocardiographic parameters establishes
      reference values in this genetically and environmentally diverse SSA population
      thereby allowing identification of "outliers" with potential cardiac disease.

PMID- 24460801
TI  - Hypoxia increases membrane metallo-endopeptidase expression in a novel lung
      cancer ex vivo model - role of tumor stroma cells.
AB  - BACKGROUND: Hypoxia-induced genes are potential targets in cancer therapy.
      Responses to hypoxia have been extensively studied in vitro, however, they may
      differ in vivo due to the specific tumor microenvironment. In this study gene
      expression profiles were obtained from fresh human lung cancer tissue fragments
      cultured ex vivo under different oxygen concentrations in order to study
      responses to hypoxia in a model that mimics human lung cancer in vivo. METHODS:
      Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were
      maintained ex vivo in normoxia or hypoxia in short-term culture. Viability,
      apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were
      studied using Affymetrix GeneChip 1.0 ST microarrays. RESULTS: Apoptosis rates
      were comparable in normoxia and hypoxia despite different oxygenation levels,
      suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in
      hypoxic compared to normoxic fragments largely overlapped with published hypoxia
      signatures. While most of these genes were up-regulated by hypoxia also in NSCLC
      cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was
      not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated
      fibroblasts isolated from non-small cell lung cancers. High MME expression was
      significantly associated with poor overall survival in 342 NSCLC patients in a
      meta-analysis of published microarray datasets. CONCLUSIONS: The novel ex vivo
      model allowed for the first time to analyze hypoxia-regulated gene expression in
      preserved human lung cancer tissue. Gene expression profiles in human hypoxic
      lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines,
      however, the elastase MME was identified as a novel hypoxia-induced gene in lung
      cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines
      in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma
      fibroblast MME expression under hypoxia might contribute to enhanced
      aggressiveness of hypoxic cancers.

PMID- 24460806
TI  - Celecoxib-induced change in atrial electrophysiologic substrate in arthritis
      patients.
AB  - BACKGROUND: Cyclooxygenase-2 inhibitors, the newest class of nonsteroidal
      antiinflammatories, pose an increased risk of adverse cardiovascular events, in
      particular atrial fibrillation (AF). We hypothesized that the COX-2 inhibitor
      celecoxib alters atrial electrophysiology, and thus promotes the development of
      AF. METHODS: Three prospective patient cohorts were created: Healthy patients (n
      = 35), inflammatory arthritis patients with no celecoxib use (n = 22), and
      inflammatory arthritis patients treated with celecoxib (n = 20). Patients were
      included in the arthritis cohorts if they were over the age of 18 and had a
      diagnosis of inflammatory arthritis. Patients in the celecoxib group must be
      actively treated with celecoxib for more than 2 months. Patients were excluded if
      they were taking antiarrhythmic mediation, had a diagnosis of AF, refractory
      hypertension, or congestive heart failure. High-resolution signal-averaged
      electrocardiogram was recorded and P-wave duration (PWD) was derived. RESULTS:
      PWD was significantly longer in inflammatory arthritis patients treated with
      celecoxib, compared to both healthy and inflammatory arthritis patients (P =
      0.049, P = 0.036). There was no difference in the PWD of healthy patients as
      compared to inflammatory arthritis patients (P = 0.916). Mean PWD (standard error
      of the mean) of the inflammatory arthritis patients treated with celecoxib was
      133.1 (2.7) ms as compared to 125.3 (1.6) ms in the healthy patients and 124.0
      (2.9) ms in the inflammatory arthritis patients. CONCLUSIONS: Given that PWD is a
      well-accepted noninvasive marker of atrial electrophysiology, our results suggest
      that these patients demonstrate adverse atrial remodeling predisposing to atrial
      arrhythmia.

PMID- 24460805
TI  - Fragmented surface ECG was a poor predictor of appropriate therapies in patients
      with Chagas' cardiomyopathy and ICD implantation (Fragmented ECG in CHAgas'
      Cardiomyopathy Study).
AB  - BACKGROUND: Main causes of death in chronic Chagas' cardiomyopathy (CChC) are
      progressive congestive heart failure and sudden cardiac death. Implantable
      cardioverter defibrillators (ICD) have been proved an effective therapy to
      prevent sudden death in patients with CChC. Identification of predictors of
      sudden death remains a challenge. OBJECTIVE: To determine whether surface
      fragmented ECG (fQRS) helps identifying patients with CChC and ICDs at higher
      risk of presenting appropriate ICD therapies. METHODS: Multicenter retrospective
      study. All patients with CChC and ICDs were analyzed. Clinical demographics,
      surface ECG, and ICD therapies were collected. RESULTS: A total of 98 patients
      were analyzed. Another four cases were excluded due to pacing dependency. Mean
      age was 55.5 +/- 10.4 years, male gender 65%, heart failure New York Heart
      Association class I 47% and II 38%. Mean left ventricular ejection fraction
      (LVEF) 39.6 +/- 11.8%. The indication for ICD was secondary prevention in 70% of
      patients. fQRS was found in 56 patients (59.6%). Location of fragmentation was
      inferior (57.1%), lateral (35.7%), and anterior (44.6%). Rsr pattern was the more
      prevalent (57.1%). Predictors of appropriate therapy in the multivariate model
      were: increased age (P = 0.01), secondary prevention indication (P = 0.01),
      ventricular pacing >50% of the time (P = 0.004), and LVEF <30% (P = 0.01). The
      presence of fQRS did not identify patients at higher risk of presenting
      appropriate therapies delivered by the ICD (P = 0.87); regardless of QRS interval
      duration. CONCLUSIONS: fQRS is highly prevalent among patients with CChC. It has
      been found a poor predictor of appropriate therapies delivered by the ICD in this
      population.

PMID- 24460808
TI  - Use of continuous ECG for improvements in assessing the standing response as a
      positive control for QT prolongation.
AB  - BACKGROUND: Standing invoked change in QT interval has been identified as a
      promising autonomic maneuver for the assessment of QT/QTc prolongation in
      patients with underlying heart abnormalities or as a positive control in healthy
      volunteers for drug studies. Criticism for its more widespread use is the high
      variability in reported results and the need for a more standardized methodology
      with defined normal ranges. METHODS: Forty healthy male subjects underwent
      continuous ECG collection on the day before dosing in a double-blind, placebo
      controlled, randomized, single ascending dose trial. A brisk supine to standing
      (3 minutes) response was conducted at three time points. Results were grouped by
      treatment cohort or assessed as a pooled group at each time point. Maximum time
      and median change from baseline (DeltaTmax QTcF, DeltaQTcF) were calculated for
      each individual over sequential 30-second periods staggered by 5 seconds.
      RESULTS: Maximum DeltaQTcF at all time points and in all groups was significant
      (i.e., the lower bound of 90% CI was > 5 milliseconds) which is the ICH E14
      regulatory requirement for a positive control. Variability of the time to maximum
      response was also reduced 9-fold by the third time period. CONCLUSIONS: Standing
      invoked DeltaQTcF can be utilized to validate the sensitivity of a study for
      assessment of the QT interval effect of drugs in early development. The
      methodology may be used to further improve its diagnostic use of long QT
      syndromes by reducing the variability and allowing adequate definition of normal
      limits.

PMID- 24460807
TI  - Single nucleotide polymorphisms in proximity to K-channel genes are associated
      with decreased longitudinal QTc variance.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common form of cardiac
      arrhythmia. Despite significant progress in identification of predisposing
      factors, the pathophysiology of AF remains to be elucidated. Previous studies
      have reported that single nucleotide polymorphisms (SNPs) in potassium-channel
      genes associate with AF and the instantaneous corrected QT interval (QTc). The
      purpose of this study was to examine the association between SNPs in proximity to
      KCNQ1, KCNH2, KCNE2, and KCNJ2 and longitudinal QTc variations in patients with
      AF. METHODS AND RESULTS: We conducted a retrospective cohort study of 800
      electrocardiograms from 93 patients with AF. All patients were Caucasian, with an
      average age of 61.2 years, and 72% were male. Of all patients, 37% had persistent
      AF, and 63% had paroxysmal AF. Following DNA extraction from blood, SNPs at the
      AF-associated loci KCNQ1, KCNH2, KCNE2, and KCNJ2 were genotyped using the
      Sequenom MassARRAY. Using a linear regression model and adapting a resampling
      inference, a decrease in longitudinal QTc variance was found to associate with
      SNPs near KCNH2 (rs10240738) and KCNJ2 (rs8079702) when adjusted for patient age,
      gender, AF type, and average QTc. On average, patients with these SNPs had a
      shorter QTc interval. In addition, we fitted a multilevel mixed effects
      regression model accounting for subject level heterogeneity and found no
      longitudinal association between presence of SNPs near K-channel genes and
      changes in QTc. CONCLUSION: Polymorphisms near specific potassium-channel genes
      in AF patients are associated with decreased longitudinal QTc variance and a
      shorter average QTc. These results support the hypothesis that effects on
      myocardial repolarization may mediate the association of these SNPs and AF.

PMID- 24460809
TI  - Very early recurrence of Takotsubo syndrome.
AB  - An 82-year-old female presented lasting chest pain for stimulation and the ECG
      revealed ventricular fibrillation and ST segment elevation, so we considered
      acute myocardial infarction. However, after the clinical condition of the patient
      improved, symptoms recurred for stimulation again on day 4. An echocardiogram
      showed left ventricular apical ballooning, so, we diagnosed her as Takotsubo
      syndrome.

PMID- 24460810
TI  - Vagal enhancement linking abnormal blood pressure response and subendocardial
      ischemia in hypertrophic cardiomyopathy.
AB  - An abnormal blood pressure response to exercise has been reported to be
      associated with left ventricular subendocardial ischemia in patients with
      hypertrophic cardiomyopathy (HCM), but the underlying mechanism remains unclear.
      We report a case of HCM with an abnormal blood pressure response and
      subendocardial ischemia, in which the analysis of heart rate variability revealed
      exercise-induced vagal enhancement. The present case highlights the possible
      mechanism linking abnormal blood pressure response and left ventricular
      subendocardial ischemia in patients with HCM.

PMID- 24460811
TI  - Mask leak increases and minute ventilation decreases when chest compressions are
      added to bag ventilation in a neonatal manikin model.
AB  - AIM: To determine changes in respiratory mechanics when chest compressions are
      added to mask ventilation, as recommended by the International Liaison Committee
      on Resuscitation (ILCOR) guidelines for newborn infants. METHODS: Using a Laerdal
      Advanced Life Support leak-free baby manikin and a 240-mL self-inflating bag, 58
      neonatal staff members were randomly paired to provide mask ventilation, followed
      by mask ventilation with chest compressions with a 1:3 ratio, for two minutes
      each. A Florian respiratory function monitor was used to measure respiratory
      mechanics, including mask leak. RESULTS: The addition of chest compressions to
      mask ventilation led to a significant reduction in inflation rate, from 63.9 to
      32.9 breaths per minute (p < 0.0001), mean airway pressure reduced from 7.6 to
      4.9 cm H2 O (p < 0.001), minute ventilation reduced from 770 to 451 mL/kg/min (p
      < 0.0001), and there was a significant increase in paired mask leak of 6.8% (p <
      0.0001). CONCLUSION: Adding chest compressions to mask ventilation, in accordance
      with the ILCOR guidelines, in a manikin model is associated with a significant
      reduction in delivered ventilation and increase in mask leak. If similar findings
      occur in human infants needing an escalation in resuscitation, there is a
      potential risk of either delay in recovery or inadequate response to
      resuscitation.

PMID- 24460812
TI  - Survey of restless legs syndrome in a pulmonary hypertension population.
AB  - INTRODUCTION: The prevalence of restless legs syndrome (RLS) varies from 5% to
      24% in the general population and is associated with a variety of medical
      disorders. However, the association between RLS and pulmonary hypertension (PH)
      is unknown. OBJECTIVES: To determine the prevalence of RLS in PH patients.
      METHODS: A cross-sectional questionnaire was given to patients with PH who
      attended the Pulmonary Hypertension Association conference. We used the RLS
      Diagnostic Index questionnaire. Demographic data included age, gender, height,
      weight, body mass index (BMI), medication list, PH World Health Organization
      (WHO) diagnosis group and current WHO functional class. RESULTS: The study
      included 128 PH patients. Most were females (86.8%) with a mean age of 49.68
      years [standard deviation (SD) 14.24]. The mean BMI was 31.3 (SD 20.46). One
      hundred and twenty-one patients (93.75%) were classified as WHO group 1
      (pulmonary arterial hypertension). Three patients were identified in WHO group 3
      (hypoxemic states), four patients in group 4 (chronic thromboemboli) and one
      patient in group 5 (2.3%, 3.1% and 0.8%, respectively). Definite RLS was found in
      16 of 128 patients with PH resulting in a prevalence of 12.5%, possible RLS in 39
      of 128 patients (30.46%) and no RLS in 73 (57.03%) patients. CONCLUSION: The
      prevalence of RLS is not increased in PH. There is a high prevalence of possible
      RLS in our study. The overall prevalence of combined definite and possible RLS is
      significant. Future research is needed to assess more patients with PH and the
      association or correlation with RLS.

PMID- 24460813
TI  - CodaChrome: a tool for the visualization of proteome conservation across all
      fully sequenced bacterial genomes.
AB  - BACKGROUND: The relationships between bacterial genomes are complicated by
      rampant horizontal gene transfer, varied selection pressures, acquisition of new
      genes, loss of genes, and divergence of genes, even in closely related lineages.
      As more and more bacterial genomes are sequenced, organizing and interpreting the
      incredible amount of relational information that connects them becomes
      increasingly difficult. RESULTS: We have developed CodaChrome
      (http://www.sourceforge.com/p/codachrome), a one-versus-all proteome comparison
      tool that allows the user to visually investigate the relationship between a
      bacterial proteome of interest and the proteomes encoded by every other bacterial
      genome recorded in GenBank in a massive interactive heat map. This tool has
      allowed us to rapidly identify the most highly conserved proteins encoded in the
      bacterial pan-genome, fast-clock genes useful for subtyping of bacterial species,
      the evolutionary history of an indel in the Sphingobium lineage, and an example
      of horizontal gene transfer from a member of the genus Enterococcus to a recent
      ancestor of Helicobacter pylori. CONCLUSION: CodaChrome is a user-friendly and
      powerful tool for simultaneously visualizing relationships between thousands of
      proteomes.

PMID- 24460814
TI  - Quantifying esophagogastric junction contractility with a novel HRM topographic
      metric, the EGJ-Contractile Integral: normative values and preliminary evaluation
      in PPI non-responders.
AB  - BACKGROUND: Despite its obvious pathophysiological relevance, the clinical
      utility of measures of esophagogastric junction (EGJ) contractility is
      unsubstantiated. High-resolution manometry (HRM) may improve upon this with its
      inherent ability to integrate the magnitude of contractility over time and length
      of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ
      contractility and test its ability distinguish among subgroups of proton pump
      inhibitor non-responders (PPI-NRs). METHODS: 75 normal controls and 88 PPI-NRs
      were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI
      therapy scored in terms of acid exposure, number of reflux events, and reflux
      symptom correlation and grouped as meeting all criteria, some criteria, or no
      criteria of abnormality. Control HRM studies were used to establish normal values
      for candidate EGJ contractility metrics, which were then compared in their
      ability to differentiate among PPI-NR subgroups. KEY RESULTS: The EGJ contractile
      integral (EGJ-CI), a metric integrating contractility across the EGJ for three
      respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from
      controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this
      measure were 39 mmHg-cm [25-55 mmHg-cm]. The correlation between the EGJ-CI and a
      previously proposed metric, the lower esophageal sphincter-pressure integral,
      that used a fixed 10 s time frame and an atmospheric as opposed to gastric
      pressure reference was weak. CONCLUSIONS & INFERENCES: Among HRM metrics tested,
      the EGJ-CI was best in distinguishing PPI-NRs meeting all criteria of abnormality
      on pH-impedance testing. Future prospective studies are required to explore its
      utility in management of broader groups of gastroesophageal reflux disease
      patients.

PMID- 24460815
TI  - Inhibition of spring viraemia of carp virus replication in an Epithelioma
      papulosum cyprini cell line by RNAi.
AB  - Spring viraemia of carp virus (SVCV) is an aetiological agent of a serious
      disease affecting carp farms in Europe and is a member of the Rhabdoviridae
      family of viruses. The genome of SVCV codes for five proteins: nucleoprotein (N),
      phosphoprotein (P), matrix protein (M), glycoprotein (G) and RNA-dependent RNA
      polymerase (L). RNA-mediated interference (RNAi) by small interfering RNAs
      (siRNAs) is a powerful tool to inhibit gene transcription and is used to study
      genes important for viral replication. In previous studies regarding another
      member of Rhabdoviridae, siRNA inhibition of the rabies virus nucleoprotein gene
      provided in vitro and in vivo protection against rabies. In this study, synthetic
      siRNA molecules were designed to target SVCV-N and SVCV-P transcripts to inhibit
      SVCV replication and were tested in an epithelioma papulosum cyprini (EPC) cell
      line. Inhibition of gene transcription was measured by real-time quantitative
      reverse-transcription PCR (RT-qPCR). The efficacy of using siRNA for inhibition
      of viral replication was analysed by RT-qPCR measurement of a reporter gene
      (glycoprotein) expression and by virus endpoint titration. Inhibition of
      nucleoprotein and phosphoprotein gene expression by siRNA reduced SVCV
      replication. However, use of tandem siRNAs that target phosphoprotein and
      nucleoprotein worked best at reducing SVCV replication.

PMID- 24460816
TI  - Exosomes: an overview of biogenesis, composition and role in ovarian cancer.
AB  - Exosomes are tiny membrane-bound vesicles that are over produced by most
      proliferating cell types during normal and pathological states. Their levels are
      up-regulated during pregnancy and disease states such as cancer. Exosomes contain
      a wide variety of proteins, lipids, RNAs, non-transcribed RNAs, microRNAs and
      small RNAs that are representative to their cellular origin and shuttle from a
      donor cell to a recipient cell. From intercellular communication to tumor
      proliferation, exosomes carry out a diverse range of functions, both helpful and
      harmful. Useful as biomarkers, exosomes may be applicable in diagnostic
      assessments as well as cell-free anti-tumor vaccines. Exosomes of ovarian cancer
      contain different set of proteins and miRNAs compared to exosomes of normal,
      cancer-free individuals. These molecules may be used as multiple "barcode" for
      the development of a diagnostic tool for early detection of ovarian cancer. 

PMID- 24460817
TI  - The significance of low-level viraemia in diverse settings: analysis of the Treat
      Asia HIV Observational Database (TAHOD) and the Australian HIV Observational
      Database (AHOD).
AB  - OBJECTIVES: The aim of the study was to assess the significance of low-level
      viraemia (LLV) and the timing of treatment change in low/middle-income country
      (L/MIC) compared with high-income country (HIC) settings. METHODS: Patients with
      virological control following commencement of combination antiretroviral therapy
      (cART) were included in the study. LLV was defined as undetectable viral load
      (<50 HIV-1 RNA copies/mL) followed by confirmed detectable viral load < 1000
      copies/mL. Virological failure was defined as viral load > 1000 copies/mL. Kaplan
      Meier plots of time to virological failure by prior LLV and income category were
      generated. Regimen changes in the setting of LLV were compared between sites.
      Sensitivity analysis of rates of LLV and virological failure by person-years and
      number of tests was conducted for differing definitions of LLV and virological
      failure. RESULTS: A total of 1748 patients from HICs and 823 patients from L/MICs
      were included in the study. One hundred and ninety-six (11.2%) HIC participants
      and 36 (4.4%) L/MIC participants experienced at least one episode of LLV. Of the
      patients who underwent regimen switch in HIC settings, the majority changed from
      a nucleoside reverse transcriptase inhibitor (NRTI)/protease inhibitor (PI)
      regimen to an NRTI/nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen
      (26.8%). Very few switches were made in L/MIC settings. Rates of LLV were
      significantly higher for HICs compared with L/MICs per 1000 person-years (28.6
      and 9.9 per 1000 person-years, respectively), but not in terms of the number of
      tests (9.4 and 7.2 per 1000 tests, respectively). Rates of virological failure
      per test were significantly higher for L/MICs compared with HICs (30.7 vs. 19.6
      per 1000 tests, respectively; P < 0.001). LLV was a significant predictor of
      virological failure at 2 years in L/MICs [0.25; 95% confidence interval (CI) 0.11
      0.50; P = 0.043] but not in HICs (0.13; 95% CI 0.08-0.22; P = 0.523).
      CONCLUSIONS: LLV is weakly predictive of virological failure at 2 years in L/MICs
      but not in HICs. This suggests that interventions targeted at subjects with LLV
      in L/MICs would help to improve treatment outcomes.

PMID- 24460819
TI  - Networking among young global health researchers through an intensive training
      approach: a mixed methods exploratory study.
AB  - BACKGROUND: Networks are increasingly regarded as essential in health research
      aimed at influencing practice and policies. Less research has focused on the role
      networking can play in researchers' careers and its broader impacts on capacity
      strengthening in health research. We used the Canadian Coalition for Global
      Health Research (CCGHR) annual Summer Institute for New Global Health Researchers
      (SIs) as an opportunity to explore networking among new global health
      researchers. METHODS: A mixed-methods exploratory study was conducted among SI
      alumni and facilitators who had participated in at least one SI between 2004 and
      2010. Alumni and facilitators completed an online short questionnaire, and a
      subset participated in an in-depth interview. Thematic analysis of the
      qualitative data was triangulated with quantitative results and CCGHR reports on
      SIs. Synthesis occurred through the development of a process model relevant to
      networking through the SIs. RESULTS: Through networking at the SIs, participants
      experienced decreased isolation and strengthened working relationships.
      Participants accessed new knowledge, opportunities, and resources through
      networking during the SI. Post-SI, participants reported ongoing contact and
      collaboration, although most participants desired more opportunities for
      interaction. They made suggestions for structural supports to networking among
      new global health researchers. CONCLUSIONS: Networking at the SI contributed
      positively to opportunities for individuals, and contributed to the formation of
      a network of global health researchers. Intentional inclusion of networking in
      health research capacity strengthening initiatives, with supportive resources and
      infrastructure could create dynamic, sustainable networks accessible to global
      health researchers around the world.

PMID- 24460820
TI  - Lamivudine compared with newer antivirals for prophylaxis of hepatitis B core
      antibody positive livers: a cost-effectiveness analysis.
AB  - There is concern over the development of de novo hepatitis B in patients
      receiving liver transplants from hepatitis B surface antigen negative, hepatitis
      B core antibody positive donors. Current practice is to place such patients on
      indefinite lamivudine prophylaxis; however, there is a small risk of breakthrough
      infection and newer antivirals for hepatitis B are available. The objective of
      this study was to determine the cost-effectiveness of lamivudine compared with
      the newer agents, tenofovir and entecavir, in the prophylaxis setting using a
      Markov model. Three strategies were examined which consisted of either lamivudine
      or entecavir monoprophylaxis with tenofovir add-on therapy after breakthrough or
      tenofovir monoprophylaxis with emtricitabine add-on therapy after breakthrough.
      In the base case scenario, lamivudine was the most cost-effective option at a
      threshold of $100 000 per quality-adjusted life-year and this remained robust
      despite parameter uncertainty. Tenofovir had an incremental cost-effectiveness
      ratio of $3 540 194.77 while other strategies were superior to entecavir therapy.
      Until drug costs decrease, lamivudine remains the most cost-effective option for
      hepatitis B prophylaxis in the liver transplant setting.

PMID- 24460818
TI  - Association between discordant immunological response to highly active anti
      retroviral therapy, regulatory T cell percentage, immune cell activation and very
      low-level viraemia in HIV-infected patients.
AB  - The mechanisms sustaining the absence of complete immune recovery in HIV-infected
      patients upon long-term effective highly active anti-retroviral therapy (HAART)
      remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level
      viraemia (VLLV) have been alternatively suspected, but rarely investigated
      simultaneously. We performed a cross-sectional study in HIV-infected aviraemic
      subjects (mean duration of HAART: 12 years) to concomitantly assess parameters
      associated independently with inadequate immunological response. Patients were
      classified as complete immunological responders (cIR, n = 48) and inadequate
      immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (>
      or < 500/mm(3)). Clinical and virological data (including very low-level
      viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes,
      including T(reg) subsets, and CD8(+) T cells was performed. Percentages of
      activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs)
      were found to be significantly elevated in iIR. Neither the percentage of
      activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the
      multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs)
      were the only two parameters associated independently with iIR [odds ratio (OR) =
      2.339, P = 0.001, and OR = 0.803, P = 0.041]. We present here the largest study
      investigating simultaneously the immune response to long-term HAART, activation
      of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia.
      Causative interactions between T(regs) and CD4(+) T cells should now be explored
      prospectively in a large patients cohort.

PMID- 24460821
TI  - The impact of shiftwork on health: a literature review.
AB  - AIMS AND OBJECTIVES: To identify the impact of shiftwork on individuals and their
      lives and to discuss the implications this has for nurses and nursing.
      BACKGROUND: The context of shiftwork in the early 21st century is changing
      rapidly, and those involved in or required to work shiftwork are now spread over
      many different sectors of the community. In the Australian community, 16% of
      workers regularly work shiftwork. Most nurses undertake shiftwork at some time in
      their career, and health services could not operate without a shiftworking
      nursing workforce. DESIGN: Narrative literature review. METHODS: A narrative
      review of journal articles was conducted. Databases searched were CINAHL, EBSCO
      Host, JSTOR, Medline/PubMed and Google Scholar. Search terms used were
      'shiftwork' and 'shift work'. Limitations included 'English language', 'published
      between 1980-2013' and 'human'. RESULTS: Reviewed for this paper were 118 studies
      that met the inclusion criteria. Results were categorised using thematic
      analysis. Themes that emerged were physical and psychosocial health, and sleep.
      Findings will be explored under these themes. CONCLUSIONS: Shiftwork research has
      mainly focussed on the physiological and psychosocial health and sleep effects.
      Absent from the literature are studies focussing on the personal experience of
      the shiftworker and how workers mediate the effects of shiftwork and how
      shiftwork fits into the rest of their lives. Therefore, it is difficult to draw
      conclusions about how people 'manage' their shiftwork, and further research needs
      to be undertaken in this area. RELEVANCE TO CLINICAL PRACTICE: Working shifts for
      nurses is a reality that comes with the profession. While there is a significant
      body of research on shiftwork, little of this has been specifically applied to
      nursing, and the implications for individual nurses needing to care for their own
      health have not been drawn.

PMID- 24460823
TI  - Salivary biomarkers of bacterial burden, inflammatory response, and tissue
      destruction in periodontitis.
AB  - AIM: Chronic periodontitis has an episodic and multifactorial character, with
      fluctuations in bacterial burden, inflammatory response, and tissue destruction.
      We investigated the association of selected salivary biomarkers with periodontal
      parameters and validated the use of a novel salivary diagnostic approach, the
      cumulative risk score (CRS), in detection of periodontitis in subjects with
      angiographically verified coronary artery disease diagnosis. MATERIALS AND
      METHODS: The concentrations of matrix metalloproteinase (MMP)-8, interleukin (IL)
      1beta, and Porphyromonas gingivalis were analysed from saliva of 493 subjects.
      The subjects participated in a detailed clinical and radiographic oral
      examination. The CRS index, combining the three salivary biomarkers, was
      calculated for each subject. RESULTS: High salivary concentrations of MMP-8, IL
      1beta, and P. gingivalis were associated with deepened periodontal pockets and
      alveolar bone loss, and MMP-8 and IL-1beta with bleeding on probing. The CRS
      index had a stronger association with moderate to severe periodontitis (OR 6.13;
      95% CI 3.11-12.09) than any of the markers alone. CONCLUSIONS: Salivary
      concentrations of MMP-8, IL-1beta, and P. gingivalis are associated with various
      clinical and radiographic measures of periodontitis. The CRS index, combining the
      three salivary biomarkers, is associated with periodontitis more strongly than
      any of the markers alone regardless of the coronary artery disease status of the
      patients.

PMID- 24460825
TI  - Does Traffic Stress Affect Distance Estimation and Recognition Accuracy in Urban
      Bus Drivers?
AB  - This study has been carried out to investigate the effect of traffic load on the
      level of blood adrenaline hormone and its influences on the distance estimation
      and recognition accuracy among urban bus drivers. The level of blood adrenaline
      hormone has been regarded as stress index. Sixty-nine urban bus drivers were
      investigated on heavy- and low-traffic days. The precision of distance estimation
      and the recognition accuracy among this population were also evaluated in both
      situations. The level of adrenaline in drivers' blood on heavy-traffic days was
      more than low-traffic days. The means of recognition accuracy and distance
      estimation precision showed that the drivers' ability has decreased on high
      traffic days as opposed to low-traffic days. The increase of the drivers' blood
      adrenaline on heavy-traffic days could make the drivers more stressed out, as
      their precision and judgment might be reduced. 

PMID- 24460824
TI  - Prospective study of maternal alcohol intake during pregnancy or lactation and
      risk of childhood asthma: the Norwegian Mother and Child Cohort Study.
AB  - BACKGROUND: Many women drink during pregnancy and lactation despite
      recommendations to abstain. In animals, alcohol exposure during pregnancy and
      lactation influences lung and immune development, plausibly increasing risk of
      asthma and lower respiratory tract infections (LRTIs). Studies in humans are few.
      METHODS: In the Norwegian Mother and Child Cohort Study, we examined maternal
      alcohol intake during pregnancy and lactation in relation to risk of current
      asthma at 36 months (49,138 children), recurrent LRTIs by 36 months (39,791
      children), and current asthma at 7 years (13,253 children). Mothers reported
      frequency and amount of alcohol intake each trimester and the first 3 months
      following delivery. We calculated adjusted relative risk (aRR), comparing
      children of drinkers to nondrinkers, using Generalized Linear Models. RESULTS: A
      total of 31.8% of mothers consumed alcohol during first trimester, 9.7% during
      second trimester, and 15.6% during third trimester. Infrequent and low-dose
      prenatal alcohol exposure showed a modest statistically significant inverse
      association with current asthma at 36 months (aRRs ~ 0.85). No association was
      seen with the highest alcohol intakes during the first trimester when alcohol
      consumption was most common. RRs of maternal alcohol intake during pregnancy with
      recurrent LRTIs were ~1, with sporadic differences in risk for some metrics of
      intake, but without any consistent pattern. For current asthma at 7 years,
      similar inverse associations were seen as with current asthma at 36 months but
      were not statistically significant. Among children breastfed throughout the first
      3 months of life, maternal alcohol intake during this time was not significantly
      associated with any of the 3 outcomes. CONCLUSIONS: The low levels of alcohol
      exposure during pregnancy or lactation observed in this cohort were not
      associated with increased risk of asthma or recurrent LRTIs. The slight inverse
      associations of infrequent or low-dose prenatal alcohol exposure with asthma may
      not be causal.

PMID- 24460822
TI  - Seq and CLIP through the miRNA world.
AB  - High-throughput sequencing of RNAs crosslinked to Argonaute proteins reveals not
      only a multitude of atypical miRNA binding sites but also of miRNA targets with
      atypical functions, and can be used to infer quantitative models of miRNA-target
      interaction strength. 

PMID- 24460826
TI  - A case of granulomatosis with polyangiitis and pyoderma gangrenosum successfully
      treated with infliximab and rituximab.
AB  - Here, we present a young male patient who was admitted with alveolar hemorrhage,
      arthritis and cutaneous lesions, who later developed bilateral orbital
      involvement and pyoderma gangrenosum (PG). He also had pathergy test positivity.
      The patient was refractory to conventional immunosuppressive therapy. Therefore,
      multiple devastating PG lesions and disease activity in granulomatosis with
      polyangiitis (GPA) were controlled with infliximab. Later, rituximab was used
      with success to prevent recurrence of symptoms. The relationship of PG with
      various autoimmune diseases is known; however, PG in GPA has been only rarely
      reported. Biologic agents might prove to be effective in GPA and PG patients who
      are refractory to standard immunosuppressive therapy. 

PMID- 24460827
TI  - SMS reminders to improve the tuberculosis cure rate in developing countries (TB
      SMS Cameroon): a protocol of a randomised control study.
AB  - BACKGROUND: Tuberculosis is a public health problem in Cameroon, just like in
      many other countries in the world. The National Tuberculosis Control Programme
      (PNLT) put in place by the state, aims to fight tuberculosis through the
      implementation of international directives (Directly Observed Treatment Short,
      DOTS). Despite the deployment of this strategy across the world, its
      implementation is difficult in the context of low-resource countries. Some
      expected results are not achieved. In Cameroon, the cure rate for patients with
      sputum positive pulmonary tuberculosis (TPM+) after 6 months is only about 65%,
      20% below the target. This is mainly due to poor patient adherence to treatment.
      By relying on the potential of mobile Health, the objective of this study is to
      evaluate the effect of SMS reminders on the cure rate of TPM + patients, measured
      using 6-month bacilloscopy. METHODS/DESIGN: This is a blinded, randomised
      controlled multicentre study carried out in Cameroon. The research hypothesis is
      that sending daily SMS messages to remind patients to take their prescribed
      tuberculosis medication, together with the standard DOTS strategy, will increase
      the cure rate from 65% (control group: DOTS, no SMS intervention) to 85%
      (intervention group: DOTS, with SMS intervention) in a group of new TPM +
      patients. In accordance with each treatment centre, the participants will be
      randomly allocated into the two groups using a computer program: the intervention
      group and the control group. A member of the research team will send daily SMS
      messages. Study data will be collected by health professionals involved in the
      care of patients. Data analysis will be done by the intention-to-treat method.
      DISCUSSION: The achieving of expected outcomes by the PNLT through implementation
      of DOTS requires several challenges. Although it has been demonstrated that the
      DOTS strategy is effective in the fight against tuberculosis, its application
      remains difficult in developing countries. This study explores the potential of
      mHealth to support DOTS strategy. It will gather new evidence on the
      effectiveness of mHealth-based interventions and SMS reminders in the improvement
      of treatment adherence and the cure rate of tuberculosis patients, especially in
      a low-resource country such as Cameroon. TRIAL REGISTRATION: The trial is
      registered on the Pan-African Clinical Trials Registry (http://www.pactr.org)
      under unique identification number: PACTR201307000583416.

PMID- 24460828
TI  - 5,10-Methylenetetrahydrofolate reductase single nucleotide polymorphisms and gene
      environment interaction analysis in non-syndromic cleft lip/palate.
AB  - Non-syndromic cleft lip/palate (NSCL/P) is a common congenital defect in Mexico.
      Periconceptional intake of folic acid (FA) may reduce the risk of this
      malformation. Although the 5,10-methylenetetrahydrofolate reductase (MTHFR)
      enzyme participates in folate metabolism, several studies failed to find any
      association between NSCL/P and the MTHFR C677T and A1298C polymorphisms. However,
      interactions among NSCL/P, MTHFR gene polymorphisms, and FA intake have not been
      explored in Mexican populations. This case-control study included 132 patients
      with NSCL/P and 370 controls from Mexico City. Maternal FA consumption during
      pregnancy was examined, as were the MTHFR C677T and A1298C polymorphisms and gene
      FA interactions. Maternal FA intake during the periconceptional period was lower
      in cases (1.5%) than in controls (13%), with the risk of delivering a child with
      NSCL/P lower in mothers who consumed FA (OR = 0.29, 95% CI: 0.19-0.44). In
      addition, the risk of NSCL/P was lower in children with the TT than the CC
      genotype of MTHFR C677T (OR = 0.39, 95% CI: 0.23-0.68), after Bonferroni
      correction and exclusion of stratification. No evidence of gene-FA interaction
      was found. These results indicate that maternal FA intake and the TT genotype of
      the MTHFR C677T polymorphism in children independently reduced the risk of NSCL/P
      in our population. 

PMID- 24460830
TI  - Reported prevalence and quantitative LC-MS methods for the analysis of veterinary
      drug residues in honey: a review.
AB  - Insect pollination increases the value and productivity of three-quarters of crop
      species grown for food. Declining beehive health in commercial apiaries has
      resulted in numerous reports from government laboratories worldwide of
      contamination with antimicrobial chemicals in honey. This review includes
      pertinent discussion of legislation and events leading to increased government
      oversight in the commercial honey market. A detailed summary of the variety and
      prevalence of veterinary drug residues being found in honey as well as a
      selection of robust quantitative and confirmatory LC-MS methods with an emphasis
      on those adopted by government testing laboratories are presented. 

PMID- 24460829
TI  - Are we missing the Institute of Medicine's mark? A systematic review of patient
      reported outcome measures assessing quality of patient-centred cancer care.
AB  - BACKGROUND: The Institute of Medicine (IOM) has endorsed six dimensions of
      patient-centredness as crucial to providing quality healthcare. These dimensions
      outline that care must be: 1) respectful to patients' values, preferences, and
      expressed needs; 2) coordinated and integrated; 3) provide information,
      communication, and education; 4) ensure physical comfort; 5) provide emotional
      support-relieving fear and anxiety; and 6) involve family and friends. However,
      whether patient-reported outcome measures (PROMs) comprehensively cover these
      dimensions remains unexplored. This systematic review examined whether PROMs
      designed to assess the quality of patient-centred cancer care addressed all six
      IOM dimensions of patient-centred care and the psychometric properties of these
      measures. METHODS: Medline, PsycINFO, Current Contents, Embase, CINAHL and Scopus
      were searched to retrieve published studies describing the development and
      psychometric properties of PROMs assessing the quality of patient-centred cancer
      care. Two authors determined if eligible PROMs included the six IOM dimensions of
      patient-centred care and evaluated the adequacy of psychometric properties based
      on recommended criteria for internal consistency, test-retest reliability,
      face/content validity, construct validity and cross-cultural adaptation. RESULTS:
      Across all 21 PROMs, the most commonly included IOM dimension of patient-centred
      care was "information, communication and education" (19 measures). In contrast,
      only five measures assessed the "involvement of family and friends." Two measures
      included one IOM-endorsed patient-centred care dimension, two measures had two
      dimensions, seven measures had three dimensions, five measures had four
      dimensions, and four measures had five dimensions. One measure, the Indicators
      (Non-small Cell Lung Cancer), covered all six IOM dimensions of patient-centred
      care, but had adequate face/content validity only. Eighteen measures met the
      recommended adequacy criteria for construct validity, 15 for face/content
      validity, seven for internal consistency, three for cross-cultural adaptation and
      no measure for test-retest reliability. CONCLUSIONS: There are no
      psychometrically rigorous PROMs developed with cancer patients that capture all
      six IOM dimensions of patient-centred care. Using more than one measure or
      expanding existing measures to cover all six patient-centred care dimensions
      could improve assessment and delivery of patient-centred care. Construction of
      new comprehensive measures with acceptable psychometric properties that can be
      used with the general cancer population may also be warranted.

PMID- 24460831
TI  - Assessment of changes in tumor heterogeneity following neoadjuvant chemotherapy
      in primary esophageal cancer.
AB  - To assess the changes in computed tomography (CT) tumor heterogeneity following
      neoadjuvant chemotherapy in esophageal cancer. Thirty-one consecutive patients
      who received neoadjuvant chemotherapy for esophageal cancer were identified.
      Analysis of primary tumor heterogeneity (texture) was performed on staging and
      post-chemotherapy CT scans. Image texture parameters (mean grey-level intensity,
      entropy, uniformity, kurtosis, skewness, standard deviation of histogram) were
      derived for different levels of image filtration (0-2.5). Proportional changes in
      each parameter following treatment were obtained. Comparison between pathological
      tumor response and texture parameters was analyzed using Mann-Whitney U-test. The
      relationship between CT texture and overall survival) was estimated using the
      Kaplan-Meier method. Tumor texture became more homogeneous after treatment with a
      significant decrease in entropy and increase in uniformity (filter 1.0 and 2.5).
      Pretreatment (filter 1.5, P = 0.006) and posttreatment standard deviation of
      histogram (filter 1.0, P = 0.009) showed a borderline association with
      pathological tumor response. A proportional change in skewness <0.39 (filter 1.0)
      was associated with improved survival (median overall survival 36.1 vs. 11.1
      months; P < 0.001). CT tumor heterogeneity decreased following neoadjuvant
      chemotherapy and has the potential to provide additional information in primary
      esophageal cancer. 

PMID- 24460832
TI  - Involvement of Rad52 in T-DNA circle formation during Agrobacterium tumefaciens
      mediated transformation of Saccharomyces cerevisiae.
AB  - Agrobacterium tumefaciens cells carrying a tumour inducing plasmid (Ti-plasmid)
      can transfer a defined region of transfer DNA (T-DNA) to plant cells as well as
      to yeast. This process of Agrobacterium-mediated transformation (AMT) eventually
      results in the incorporation of the T-DNA in the genomic DNA of the recipient
      cells. All available evidence indicates that T-strand transfer closely resembles
      conjugal DNA transfer as found between Gram-negative bacteria. However, where
      conjugal plasmid DNA transfer starts via relaxase-mediated processing of a single
      origin of transfer (oriT), the T-DNA is flanked by two imperfect direct border
      repeats which are both substrates for the Ti-plasmid encoded relaxase VirD2.
      Yeast was used as a model system to investigate the requirements of the recipient
      cell for the formation of T-DNA circles after AMT. It was found that, despite the
      absence of self-homology on the T-DNA, the homologous repair proteins Rad52 and
      Rad51 are involved in T-DNA circle formation. A model is presented involving the
      formation of T-DNA concatemers derived from T-strands by a process of strand
      transfer catalysed by VirD2. These concatemers are then resolved into T-DNA
      circles by homologous recombination in the recipient cell. 

PMID- 24460833
TI  - Large-scale analysis of differential gene expression in coffee genotypes
      resistant and susceptible to leaf miner-toward the identification of candidate
      genes for marker assisted-selection.
AB  - BACKGROUND: A successful development of herbivorous insects into plant tissues
      depends on coordination of metabolic processes. Plants have evolved complex
      mechanisms to recognize such attacks, and to trigger a defense response. To
      understand the transcriptional basis of this response, we compare gene expression
      profiles of two coffee genotypes, susceptible and resistant to leaf miner
      (Leucoptera coffella). A total of 22000 EST sequences from the Coffee Genome
      Database were selected for a microarray analysis. Fluorescence probes were
      synthesized using mRNA from the infested and non-infested coffee plants. Array
      hybridization, scanning and data normalization were performed using Nimble
      Scan(r) e ArrayStar(r) platforms. Genes with foldchange values +/-2 were
      considered differentially expressed. A validation of 18 differentially expressed
      genes was performed in infected plants using qRT-PCR approach. RESULTS: The
      microarray analysis indicated that resistant plants differ in gene expression
      profile. We identified relevant transcriptional changes in defense strategies
      before insect attack. Expression changes (>2.00-fold) were found in resistant
      plants for 2137 genes (1266 up-regulated and 873 down-regulated). Up-regulated
      genes include those responsible for defense mechanisms, hypersensitive response
      and genes involved with cellular function and maintenance. Also, our analyses
      indicated that differential expression profiles between resistant and susceptible
      genotypes are observed in the absence of leaf-miner, indicating that defense is
      already build up in resistant plants, as a priming mechanism. Validation of
      selected genes pointed to four selected genes as suitable candidates for markers
      in assisted-selection of novel cultivars. CONCLUSIONS: Our results show evidences
      that coffee defense responses against leaf-miner attack are balanced with other
      cellular functions. Also analyses suggest a major metabolic reconfiguration that
      highlights the complexity of this response.

PMID- 24460835
TI  - Gastrointestinal: endoscopic ultrasound of a pancreatic lesion in situs inversus.

PMID- 24460834
TI  - CNX-012-570, a direct AMPK activator provides strong glycemic and lipid control
      along with significant reduction in body weight; studies from both diet-induced
      obese mice and db/db mice models.
AB  - OBJECTIVES: AMP activated protein kinase (AMPK) regulates the coordination of
      anabolic and catabolic processes and is an attractive therapeutic target for
      T2DM, obesity and metabolic syndrome. We report the anti-hyperglycemic and anti
      hyperlipidemic effects of CNX-012-570 is an orally bioavailable small molecule
      (molecular weight of 530 Daltons) that directly activates AMPK in DIO and db/db
      animal models of diabetes. METHODS: Activity and efficacy of the compound was
      tested in cell based as well as cell free systems in vitro. Male C57BL/6 mice fed
      with high fat diet (HFD) were assigned to either vehicle or CNX-012-570 (3 mg/kg,
      orally once a day) for 8 weeks (n = 8). Genetically diabetic db/db mice on chow
      diet were dosed with vehicle control or CNX-012-570 (2.5 mg/kg, orally once a
      day) for 6 weeks (n = 8). RESULTS: CNX-012-570 is a highly potent and orally
      bioavailable compound activating AMPK in both cell and cell free systems. It
      inhibits lipolysis (33%) and gluconeogenesis (28%) in 3T3L1 cells and rat primary
      hepatocytes respectively. The efficacy of the molecule was translated to both DIO
      and db/db animal models of diabetes. CNX-012-570 has reduced fasting blood
      glucose levels by 14%, body weight by 24% and fasting serum triglycerides (TG) by
      24%. CNX-012-570 showed a 22% reduction in fed serum cholesterol levels and 19%
      increase in HDL levels.In db/db mice model, CNX-012-570 has shown 18% decrease in
      fed glucose and 32% decrease in fasting glucose with a 2.57% reduction in
      absolute HbA1c. Decrease in serum insulin and glucose AUC indicates the increased
      insulin sensitivity. Body weight was reduced by 13% with increased browning of
      adipose tissue and decreased inguinal and mesenteric fat mass. There was
      significant reduction in liver TG and liver total cholesterol. CONCLUSIONS: CNX
      012-570 has the potential to control hyperglycemia and hyperlipidemia. It also
      reduces body weight gain with an additional benefit of minimizing cardiovascular
      risks in diabetics.

PMID- 24460836
TI  - Gastrointestinal: diaphragm disease: emerging cause of gastrointestinal
      obstruction and bleeding.

PMID- 24460837
TI  - Gastrointestinal: case of accidentally discovered splenic epidermoid cyst with
      serum CA19-9 elevation.

PMID- 24460838
TI  - Hepatobiliary and pancreatic: cyst of the cystic duct.

PMID- 24460839
TI  - Hepatobiliary and pancreatic: liver transplantation for massive hepatic
      lymphangiomatosis.

PMID- 24460841
TI  - Association of the availability of beer, wine, and liquor outlets with beverage
      specific alcohol consumption: a cohort study.
AB  - BACKGROUND: Little evidence exists on whether beverage-specific alcohol
      availability is associated with beverage-specific consumption. We longitudinally
      examined whether the number and change in number of beer, wine, and liquor
      outlets near one's home are associated with alcohol consumption by beverage type.
      METHODS: The study population consisted of 28,074 women and 6,639 men of the
      Finnish Public Sector Study who reported their alcohol use at baseline (in
      2004/2005) and follow-up (in 2008/2009). The coordinates of their residence and
      alcohol outlets during the study period were obtained from national registers.
      Associations of the number and change in the number of beer, wine, and liquor
      outlets with beer, wine, and liquor consumption were analyzed using 2-level
      cumulative logistic regression adjusted for individual- and area-level
      characteristics. RESULTS: Having >=3 wine outlets within 0.5 km of home was
      associated with a higher likelihood of wine consumption compared with having no
      outlets within 0.5 km: the cumulative odds ratios (CORs) 1.20 (95% confidence
      interval [CI] 1.10 to 1.31) in women and 1.29 (95% CI 1.08 to 1.56) in men. For
      an increase in the number of wine outlets, the COR for wine consumption was 1.16
      (95% CI 1.08 to 1.25) among all women and 1.10 (95% CI 1.01 to 1.21) among those
      who did not move between surveys. No corresponding beverage-specific outlet
      consumption associations were observed for beer and liquor. CONCLUSIONS: A high
      number of wine outlets near home may increase wine consumption among men and
      women. In addition, an increase in the number of wine outlets may add to its
      consumption among women, independent of the individuals' choice to move to areas
      of better availability.

PMID- 24460840
TI  - Extracellular signal-regulated kinase-5: Novel mediator of insulin and tumor
      necrosis factor alpha-stimulated vascular cell adhesion molecule-1 expression in
      vascular cells.
AB  - BACKGROUND: Atherosclerosis may be stimulated by the increased presence of
      insulin and tumor necrosis-factor-alpha (TNFalpha) with subsequent expression of
      vascular cell adhesion molecule-1 (VCAM-1). We hypothesized that extracellular
      signal-regulated kinase-5 (ERK5) plays an important role in insulin and TNFalpha
      stimulated total and cell surface VCAM-1 expression. METHODS: Rat aorta vascular
      endothelial cells were first transfected with either no inhibitory RNA, inactive
      (scrambled) inhibitory ERK5 RNA (scERK5) or active inhibitory ERK5 RNA (siERK5)
      and then treated with either (i) no analog; (ii) insulin (1 nM), or TNFalpha (1
      ng/mL) alone, or (iii) insulin plus TNFalpha for 6 h. Thereafter either total
      VCAM-1 protein or surface VCAM-1 protein was determined. RESULTS: Genetic
      inhibition of ERK5 decreased TNFalpha-stimulated total VCAM-1 expression by 57%
      and surface expression by 27%. In contrast, genetic inhibition of ERK5 did not
      significantly decrease insulin-stimulated total or surface VCAM-1 expression.
      Interestingly, genetic inhibition of ERK5 did not significantly decrease insulin
      plus TNFalpha-stimulated total VCAM-1 expression, but significantly (P < 0.05)
      decreased insulin plus TNFalpha-stimulated surface VCAM-1 expression 41%.
      CONCLUSIONS: We report here that ERK5 plays a minor role in insulin-stimulation
      of VCAM-1, but plays a significant role in TNFalpha-stimulation of both total and
      cell surface VCAM-1 protein expression. Taken together, these results demonstrate
      that not only does ERK5 have differential mediation of insulin and TNFalpha
      stimulated VCAM-1 expression, but also has differential regulation of insulin
      plus TNFalpha-stimulated total and surface VCAM-1 expression, suggesting that
      other intermediates of the insulin and TNFalpha intracellular pathways are
      contributing to atherogenesis.

PMID- 24460842
TI  - Gene expression pattern of Treg and TCR Vgamma subfamily T cells before and after
      specific immunotherapy in allergic rhinitis.
AB  - BACKGROUND: T regulatory cell (Treg) plays a critical role in respiratory allergy
      and allergen-specific immunotherapy (SIT), and gammadelta T cells might
      participate in mediating Treg quantity and/or function in some immunological
      diseases. To further characterize whether gammadelta T cells could influence Treg
      in allergic rhinitis (AR) and SIT, we investigated the expression pattern of
      Treg's Foxp3 gene and gammadelta T cell receptor (TCR) Vgamma subfamily genes in
      peripheral blood mononuclear cells (PBMCs) of AR patients before and after SIT.
      METHODS: Eighteen AR patients undergoing effective SIT with house dust mite
      extract for one year were recruited. Visual Analogue Scale (VAS) was applied to
      evaluate the severity. Immunofluorescence quantification analysis was performed
      to determine the serum specific IgE (sIgE) content. Real-time PCR was used to
      detect the expression levels of Foxp3 and TCR Vgamma subfamilies. Ten healthy
      volunteers were recruited as the controls. RESULTS: Nasal uni-VAS score after SIT
      was significantly lower than that before SIT, while serum sIgE content was
      similar before and after SIT. Expression levels of Foxp3 and TCR Vgamma
      subfamilies in AR patients before treatment were significantly lower than those
      in healthy subjects. Expression levels of VgammaI and II were similar before and
      after SIT, while expression levels of Foxp3 and VgammaIII after SIT were
      significantly higher than those before. Before SIT, the significant positive
      correlation was observed between expression levels of Foxp3 and VgammaI, II, III,
      while negative correlation was observed between Foxp3, VgammaIII and VAS. After
      SIT, the significant positive correlation between expression levels of Foxp3 and
      VgammaIII and negative correlation between Foxp3, VgammaIII and VAS were
      observed. CONCLUSIONS: Treg and Vgamma subfamily T cells were in a dynamic
      equilibrium in AR patients before and after effective immunotherapy for one year.
      The early improvement of symptoms following immunotherapy might be independent of
      the serum sIgE content in AR patients, but associated with the reconstitution of
      T cell immunity.

PMID- 24460843
TI  - Oxalate at physiological urine concentrations induces oxidative injury in renal
      epithelial cells: effect of alpha-tocopherol and ascorbic acid.
AB  - OBJECTIVES: To test our hypothesis that physiological levels of urinary oxalate
      induce oxidative renal cell injury, as studies to date have shown that oxalate
      causes oxidative injury only at supra-physiological levels. To study the combined
      effect of alpha-tocopherol and ascorbic acid against oxalate-induced oxidative
      injury, as oxalate-induced oxidative cell injury is known to promote initial
      attachment of calcium oxalate crystals to injured renal tubules and subsequent
      development of kidney stones. MATERIALS AND METHODS: Cultures of normal
      (antioxidant-undepleted) and antioxidant-depleted LLC-PK1 cells were exposed to
      oxalate at human physiological urine concentrations. After exposure, markers of
      oxidative stress and cell injury were measured in the cells and media,
      respectively. In addition, we also evaluated the combined effects of alpha
      tocopherol and ascorbic acid on oxalate-induced oxidative cell injury. RESULTS:
      Exposure of renal cells to oxalate at urinary physiological levels increased the
      oxidative cell injury as assessed by increased lactate dehydrogenase (LDH)
      leakage and increased lipid hydroperoxide in the renal cells; however, this
      effect was not seen until 24 h after oxalate exposure, at which point the injury
      was milder. On the other hand, when cellular reduced glutathione (GSH) and
      catalase were depleted in renal epithelial cells with pharmacological inhibitors,
      the physiological levels of urinary oxalate caused significant oxidative cell
      injury at 24 h, and remarkably, when additional endogenous antioxidants were
      depleted, the oxalate at the upper limit of normal 24 h urine caused a
      significant amount of cell injury in a shorter period of time, which was
      comparable to that seen in cells exposed to higher levels of oxalate. Exposure of
      LLC-PK1 cells to oxalate resulted in increased levels of H2 O2 and lipid
      hydroperoxide, correlating with increased release of cell injury markers,
      including LDH, alkaline phosphate, and gamma-glutamyl transpeptidase from renal
      tubular epithelial cells. Oxalate exposure decreased the activity and protein
      expression of superoxide dismutase and glutathione peroxidase in a time-dependent
      manner. LLC-PK1 cells treated with oxalate and either alpha-tocopherol or
      ascorbic acid alone exhibited a significant decrease in oxidative cell injury and
      restored endogenous renal antioxidants towards normal levels, and interestingly,
      combined treatment with alpha-tocopherol and ascorbic was more efficient at
      preventing oxalate-induced toxicity than treatment with either agent alone.
      CONCLUSION: To our knowledge this is the first study to show that oxalate alone
      at human physiological urine concentrations (in the absence of calcium oxalate
      crystal formation), induced oxidative renal injury in renal epithelial cells when
      endogenous antioxidants are depleted. Our data further suggests that a
      combination of alpha-tocopherol and ascorbic acid may be more effective than each
      individual agent in reducing oxalate-induced oxidative renal injury and
      subsequent calcium oxalate crystal deposition in recurrent stone formers.

PMID- 24460844
TI  - Accidental cold-related injury leading to hospitalization in northern Sweden: an
      eight-year retrospective analysis.
AB  - BACKGROUND: Cold injuries are rare but important causes of hospitalization. We
      aimed to identify the magnitude of cold injury hospitalization, and assess
      causes, associated factors and treatment routines in a subarctic region. METHODS:
      In this retrospective analysis of hospital records from the 4 northernmost
      counties in Sweden, cases from 2000-2007 were identified from the hospital
      registry by diagnosis codes for accidental hypothermia, frostbite, and cold-water
      drowning. Results were analyzed for pre-hospital site events, clinical events in
      hospital, and complications observed with mild (temperature 34.9 - 32 degrees C),
      moderate (31.9 - 28 degrees C) and severe (<28 degrees C), hypothermia as well as
      for frostbite and cold-water drowning. RESULTS: From the 362 cases, average
      annual incidences for hypothermia, frostbite, and cold-water drowning were
      estimated to be 3.4/100,000, 1.5/100,000, and 0.8/100,000 inhabitants,
      respectively. Annual frequencies for hypothermia hospitalizations increased by
      approximately 3 cases/year during the study period. Twenty percent of the
      hypothermia cases were mild, 40% moderate, and 24% severe. For 12%, the lowest
      documented core temperature was 35 degrees C or higher, for 4% there was no
      temperature documented. Body core temperature was seldom measured in pre-hospital
      locations. Of 362 cold injury admissions, 17 (5%) died in hospital related to
      their injuries. Associated co-factors and co-morbidities included ethanol
      consumption, dementia, and psychiatric diagnosis. CONCLUSIONS: The incidence of
      accidental hypothermia seems to be increasing in this studied sub-arctic region.
      Likely associated factors are recognized (ethanol intake, dementia, and
      psychiatric diagnosis).

PMID- 24460845
TI  - Effectiveness and cost-effectiveness of a telehealth intervention to support the
      management of long-term conditions: study protocol for two linked randomized
      controlled trials.
AB  - BACKGROUND: As the population ages, more people are suffering from long-term
      health conditions (LTCs). Health services around the world are exploring new ways
      of supporting people with LTCs and there is great interest in the use of
      telehealth: technologies such as the Internet, telephone and home self
      monitoring. METHODS/DESIGN: This study aims to evaluate the effectiveness and
      cost-effectiveness of a telehealth intervention delivered by NHS Direct to
      support patients with LTCs. Two randomized controlled trials will be conducted in
      parallel, recruiting patients with two exemplar LTCs: depression or raised
      cardiovascular disease (CVD) risk. A total of 1,200 patients will be recruited
      from approximately 42 general practices near Bristol, Sheffield and Southampton,
      UK. Participants will be randomly allocated to either usual care (control group)
      or usual care plus the NHS Direct Healthlines Service (intervention group). The
      intervention is based on a conceptual model incorporating promotion of self
      management, optimisation of treatment, coordination of care and engagement of
      patients and general practitioners. Participants will be provided with tailored
      help, combining telephone advice from health information advisors with support to
      use a range of online resources. Participants will access the service for 12
      months. Outcomes will be collected at baseline, four, eight and 12 months for the
      depression trial and baseline, six and 12 months for the CVD risk trial. The
      primary outcome will be the proportion of patients responding to treatment,
      defined in the depression trial as a PHQ-9 score <10 and an absolute reduction in
      PHQ-9 >=5 after 4 months, and in the CVD risk trial as maintenance or reduction
      of 10-year CVD risk after 12 months. The study will also assess whether the
      intervention is cost-effective from the perspective of the NHS and personal
      social services. An embedded qualitative interview study will explore healthcare
      professionals' and patients' views of the intervention. DISCUSSION: This study
      evaluates a complex telehealth intervention which combines evidence-based
      components and is delivered by an established healthcare organisation. The study
      will also analyse health economic information. In doing so, the study hopes to
      address some of the limitations of previous research by demonstrating the
      effectiveness and cost-effectiveness of a real world telehealth intervention.
      TRIAL REGISTRATION: Current Controlled Trials: Depression trial ISRCTN14172341
      and cardiovascular disease risk trial ISRCTN27508731.

PMID- 24460847
TI  - Brain gamma-aminobutyric acid: a neglected role in impulsivity.
AB  - The investigation of impulsivity as a core marker of several major
      neuropsychiatric disorders has been greatly influenced by the therapeutic
      efficacy of drugs that block the reuptake of dopamine and noradrenaline in the
      brain. As a result, research into the neural mechanisms of impulsivity has
      focused on the catecholamine systems as the loci responsible for the expression
      of impulsive behaviour and the primary mechanism of action of clinically
      effective drugs for attention-deficit hyperactivity disorder (ADHD). However,
      abnormalities in the catecholamine systems alone are unlikely to account for the
      full diversity and complexity of impulsivity subtypes, nor can they fully explain
      co-morbid brain disorders such as drug addiction. Here we review the lesser
      studied role of gamma-aminobutyric acid (GABA) in impulsivity, a major target of
      the dopaminergic and noradrenergic systems in the prefrontal cortex and striatum,
      and consider how abnormalities in this inhibitory neurotransmitter might
      contribute to several forms of impulsive behaviour in humans and experimental
      animals. Our analysis reveals several promising leads for future research that
      may help inform the development of new therapies for disorders of impulse
      control. 

PMID- 24460846
TI  - Symptom cluster, healthcare use and mortality in patients with severe chronic
      obstructive pulmonary disease.
AB  - AIMS AND OBJECTIVES: To examine how subgroups of patients with chronic
      obstructive pulmonary disease, identified by ratings of symptoms (dyspnoea,
      anxiety, depression and fatigue), affect healthcare use and mortality.
      BACKGROUND: People with chronic obstructive pulmonary disease often experience
      multiple symptoms. The importance of multiple symptoms and symptom clusters has
      received increased attention. However, little is known about symptom clusters and
      their effect on healthcare use and mortality in this population. DESIGN:
      Descriptive cross-sectional study. METHODS: This secondary data analysis used
      data from the National Emphysema Treatment Trial. Participants (n = 597) had
      severe chronic obstructive pulmonary disease. Descriptive and inferential
      statistics were used to analyse the data that were drawn from structured
      interviews, questionnaires and clinical measures. RESULTS: Three subgroup
      clusters emerged based on four symptom ratings. Mean age, proportion with higher
      education, proportion using oxygen, disease severity, exercise capacity and
      quality of life differed significantly between subgroups. Participants with high
      levels of symptoms used healthcare services more and were more likely to have
      died at the five-year follow-up than those with low levels of symptoms. Symptom
      cluster subgroups had more significant relationship with mortality than single
      symptoms. CONCLUSION: Patients with high levels of symptoms require greater
      clinical attention. RELEVANCE TO CLINICAL PRACTICE: Understanding subgroups of
      patients, based on symptom ratings and their adverse effect on outcomes, may
      enable healthcare providers to assess multiple symptoms and identify subgroups of
      patients at risk of increased healthcare use and mortality. Targeting modifiable
      symptoms within the cluster may be more beneficial than focusing on a single
      symptom for certain health-related outcome.

PMID- 24460848
TI  - Working memory and alcohol use in at-risk adolescents: a 2-year follow-up.
AB  - BACKGROUND: Previous research has identified working memory (WM) as a possible
      risk factor for problem drinking in adolescence. At the same time, results
      suggest that WM functioning is negatively influenced by the use of alcohol. To
      get a better understanding of the nature of this relationship, the present study
      examined the prospective bidirectional association between alcohol use and WM in
      a sample of young adolescents at risk for problem drinking. METHODS: Adolescents
      were all 8th graders from 17 different Special Education Schools (for youth with
      externalizing behavior problems). At the beginning of the study, 374 adolescents
      participated (mean age of 13.6 years). Approximately every 6 months, adolescents
      completed a questionnaire to establish alcohol use and a Self-Ordered Pointing
      Task (SOPT) to assess WM. RESULTS: Cross-lagged analyses revealed that alcohol
      use at T1 negatively predicted WM functioning 6 months later (p < 0.001). WM
      functioning at T2 and at T3 predicted alcohol use 6 months later (p < 0.01).
      CONCLUSIONS: WM functioning has been identified as both risk factor for and as
      function negatively influenced by alcohol use. Findings indicate that early
      alcohol use in at-risk adolescents negatively influences the development of
      subsequent WM functioning, which in turn constitutes as a risk factor for later
      alcohol use problems. Implications for early interventions are discussed.

PMID- 24460849
TI  - Alternations in genes expression of pathway signaling in esophageal tissue with
      atresia: results of expression microarray profiling.
AB  - Esophageal atresia (EA) is a congenital defect of the esophagus involving the
      interruption of the esophagus with or without connection to the trachea
      (tracheoesophageal fistula [TEF]). EA/TEF may occur as an isolated anomaly, may
      be part of a complex of congenital defects (syndromic), or may develop within the
      context of a known syndrome or association. The molecular mechanisms underlying
      the development of EA are poorly understood. It is supposed that a combination of
      multigenic factors and epigenetic modification of genes play a role in its
      etiology. The aim of our work was to assess the human gene expression microarray
      study in esophageal tissue samples. Total RNA was extracted from 26 lower pouches
      of esophageal tissue collected during thoracoscopic EA repair in neonates with
      the isolated (IEA) and the syndromic form (SEA). We identified 787 downregulated
      and 841 upregulated transcripts between SEA and controls, and about 817
      downregulated and 765 upregulated probes between IEA and controls. Fifty percent
      of these genes showed differential expression specific for either IEA or SEA.
      Functional pathway analysis revealed substantial enrichment for Wnt and Sonic
      hedgehog, as well as cytokine and chemokine signaling pathways. Moreover, we
      performed reverse transcription polymerase chain reaction study in a group of SHH
      and Wnt pathways genes with differential expression in microarray profiling to
      confirm the microarray expression results. We verified the altered expression in
      SFRP2 gene from the Wnt pathway as well as SHH, GLI1, GLI2, and GLI3 from the
      Sonic hedgehog pathway. The results suggest an important role of these pathways
      and genes for EA/TEF etiology. 

PMID- 24460850
TI  - The interaction between beta-3 adrenergic receptor polymorphism and obesity to
      periodontal disease in community-dwelling elderly Japanese.
AB  - OBJECTIVES: The purpose of this study was to elucidate whether the association
      between beta-3 adrenergic receptor polymorphism and periodontal disease is
      modified by body weight. MATERIAL AND METHODS: We enrolled 332 postmenopausal
      women and determined their HbA1C levels (%) and beta-3 adrenergic receptor
      (rs4994) genotypes. Periodontal parameters including clinical attachment level
      (CAL) were measured. After selecting subjects for each body mass index (BMI)
      level, the prevalence rate ratio (PRR) by multiple Poisson regression analysis
      was calculated to evaluate the relationship between periodontal disease and beta
      3 adrenergic receptor polymorphism. The number of sites with CAL>=6 mm was used
      as a dependent variable, and beta-3 adrenergic receptor genotype [categorized as
      Arg non-carriers (reference) or Arg carriers], age (y) and HbA1C (%) were adopted
      as independent variables. We converted the number of probing sites (n) to an
      offset variable. RESULTS: The PRR of the beta-3 adrenergic receptor genotype for
      the number of sites of CAL>=6 mm showed a positive association in subjects with
      BMI>=25.0 and increased markedly with BMI. The PRR in subjects with BMI>=30 was
      3.10 (p < 0.0001). CONCLUSION: This study indicates a positive association
      between periodontal disease and the beta-3 adrenergic receptor genotype in obese
      individuals.

PMID- 24460851
TI  - Selective inhibition of FAAH produces antidiarrheal and antinociceptive effect
      mediated by endocannabinoids and cannabinoid-like fatty acid amides.
AB  - BACKGROUND: The endogenous cannabinoid system (ECS) plays a crucial role in
      multiple physiological processes in the central nervous system and in the
      periphery. The discovery that selective cannabinoid (CB) receptor agonists exert
      a potent inhibitory action on gastrointestinal (GI) motility and pain has placed
      the ECS in the center of attention as a possible target for the treatment of
      functional GI diseases. However, side effects of CB agonists prompted the search
      for novel therapeutic targets. Here, the effect of PF-3845, a potent and
      selective fatty acid amide hydrolase (FAAH) inhibitor in the GI tract was
      investigated. METHODS: The effect of PF-3845 on GI motility was characterized in
      vitro and in vivo, using mouse models that mimic physiological and
      pathophysiological conditions. The antinociceptive action of PF-3845 was
      evaluated on the basis of behavioral pain models. Endocannabinoid degradation
      product levels after inhibition of FAAH were quantified using HPLC-MS/MS. KEY
      RESULTS: PF-3845 significantly inhibited mouse colonic motility in vitro and in
      vivo. Selective inhibition of FAAH reversed hypermotility and reduced pain in
      mouse models mimicking functional GI disorders. The effects of PF-3845 were
      mediated by endogenous CBs and non-CB lipophilic compounds via classical (CB1)
      and atypical CB receptors. CONCLUSIONS & INFERENCES: These data expand our
      understanding of the ECS function and provide a novel framework for the
      development of future potential treatments of functional GI disorders.

PMID- 24460852
TI  - Is the health-related quality of life and functional status of patients with
      psoriatic arthritis worse than that of patients with psoriasis alone?
AB  - AIM: The aim of this study was to compare the health-related quality of life and
      functional status of patients with psoriasis (Ps), psoriatic arthritis (PsA) and
      control subjects. METHOD: Eighty patients with PsA, 40 patients with Ps and 40
      healthy subjects were included. Physical functions were evaluated with the Health
      Assessment Questionnaire for Spondyloarthropathies (HAQ-S) while life
      satisfaction was evaluated with the Psoriatic Arthritis Quality of Life (PsAQoL)
      questionnaire. The Disease Activity Score 28 (DAS28), Disease Activity Index for
      the Assessment of Reactive Arthritis (DAREA), Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-C
      Reactive Protein (ASDAS-CRP), Maastrich Ankylosing Spondylitis Enthesitis Score
      (MASES) and visual analog scale-pain were calculated. RESULTS: The HAQ-S data
      revealed that physical functional status in the PsA group was worse than the Ps
      and control groups (mean scores: 0.5 +/- 0.5, 0.2 +/- 0.5 and 0.1 +/- 0.3,
      respectively). The PsAQoL data revealed a worse quality of life in the PsA and Ps
      groups than in the control group but the same quality of life in the PsA and Ps
      groups (mean scores: 6.9 +/- 5.4, 7 +/- 5.9 and 3.3 +/- 4.2, respectively). Both
      the HAQ-S and PsAQoL data were found to be moderately to weakly correlated with
      disease activity measures (DAS28, DAREA, BASDAI, ASDAS-CRP), pain and enthesitis.
      CONCLUSION: Patients with Ps and PsA had worse quality of life and patients with
      PsA had worse functional status than healthy individuals. Although Ps patients
      with arthritis had a worse functional status than the ones without arthritis,
      quality of life according to PSAQoL was found to be similar between them.

PMID- 24460854
TI  - Effects of Long-Term Dust Exposure on Human Respiratory System Health in Minqin
      County, China.
AB  - The aim of this study was to assess the effects of long-term sand dust exposure
      on human respiratory health. Dust events break out frequently in Minqin County,
      northwest China, whereas Pingliang City, northwest China, is rarely influenced by
      dust events. Therefore, Minqin and Pingliang were selected as sand dust exposure
      region and control area, respectively. The incidence of respiratory system
      diseases and symptoms was determined through a structured respiratory health
      questionnaire (ATS-DLD-78-A) and personal interviews. The subjects comprised 728
      farmers (Minqin, 424; Pingliang, 304) aged 40 years or older, who had
      nondocumented occupational history to industrial dust exposure. Prevalences (odds
      ratio [OR], 95% confidence interval [CI]) of chronic rhinitis, chronic
      bronchitis, and chronic cough increased 9.6% (3.141, 1.776-5.555), 7.5% (2.468,
      1.421-4.286), and 10.2% (1.787, 1.246-2.563) in Minqin comparison with Pingliang,
      respectively, and the differences were significant (p <.01).

PMID- 24460855
TI  - Skin-Tissue-sparing Excision with Electrosurgical Peeling (STEEP): a surgical
      treatment option for severe hidradenitis suppurativa Hurley stage II/III.
AB  - BACKGROUND: Surgery is the only curative treatment for removal of the persistent
      sinus tracts in the skin that are characteristic of severe hidradenitis
      suppurativa (HS). Complete resection of the affected tissue by wide excision is
      currently regarded as the preferred surgical technique in these cases. However,
      relatively large amounts of healthy tissue are removed with this method and
      suitable skin-tissue-saving techniques aiming at creating less-extensive surgical
      defects are therefore needed in severe HS. METHOD: We describe a skin-tissue
      saving surgical technique for HS Hurley stage II-III disease: the Skin-Tissue
      sparing Excision with Electrosurgical Peeling (STEEP) procedure. DISCUSSION: In
      contrast to wide excisions that generally reach into the deep subcutaneous fat,
      the fat is maximally spared with the STEEP procedure by performing successive
      tangential excisions of lesional tissue until the epithelialized bottom of the
      sinus tracts has been reached. From here, secondary intention healing can occur.
      In addition, fibrotic tissue is completely removed in the same manner as this
      also serves as a source of recurrence. This tissue-sparing technique results in
      low recurrence rates, high patient satisfaction with relatively short healing
      times and favourable cosmetic outcomes without contractures.

PMID- 24460856
TI  - Accelerated evolution of the mitochondrial genome in an alloplasmic line of durum
      wheat.
AB  - BACKGROUND: Wheat is an excellent plant species for nuclear mitochondrial
      interaction studies due to availability of large collection of alloplasmic lines.
      These lines exhibit different vegetative and physiological properties than their
      parents. To investigate the level of sequence changes introduced into the
      mitochondrial genome under the alloplasmic condition, three mitochondrial genomes
      of the Triticum-Aegilops species were sequenced: 1) durum alloplasmic line with
      the Ae. longissima cytoplasm that carries the T. turgidum nucleus designated as
      (lo) durum, 2) the cytoplasmic donor line, and 3) the nuclear donor line.
      RESULTS: The mitochondrial genome of the T. turgidum was 451,678 bp in length
      with high structural and nucleotide identity to the previously characterized T.
      aestivum genome. The assembled mitochondrial genome of the (lo) durum and the Ae.
      longissima were 431,959 bp and 399,005 bp in size, respectively. The high
      sequence coverage for all three genomes allowed analysis of heteroplasmy within
      each genome. The mitochondrial genome structure in the alloplasmic line was
      genetically distant from both maternal and paternal genomes. The alloplasmic
      durum and the Ae. longissima carry the same versions of atp6, nad6, rps19-p, cob
      and cox2 exon 2 which are different from the T. turgidum parent. Evidence of
      paternal leakage was also observed by analyzing nad9 and orf359 among all three
      lines. Nucleotide search identified a number of open reading frames, of which 27
      were specific to the (lo) durum line. CONCLUSIONS: Several heteroplasmic regions
      were observed within genes and intergenic regions of the mitochondrial genomes of
      all three lines. The number of rearrangements and nucleotide changes in the
      mitochondrial genome of the alloplasmic line that have occurred in less than half
      a century was significant considering the high sequence conservation between the
      T. turgidum and the T. aestivum that diverged from each other 10,000 years ago.
      We showed that the changes in genes were not limited to paternal leakage but were
      sufficiently significant to suggest that other mechanisms, such as recombination
      and mutation, were responsible. The newly formed ORFs, differences in gene
      sequences and copy numbers, heteroplasmy, and substoichiometric changes show the
      potential of the alloplasmic condition to accelerate evolution towards forming
      new mitochondrial genomes.

PMID- 24460857
TI  - Alterations in immune cell subsets and their cytokine secretion profile in
      childhood idiopathic thrombocytopenic purpura (ITP).
AB  - Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children
      characterized by the breakdown of immune tolerance. This work is designed to
      explore the contribution of different lymphocyte subsets in acute and chronic ITP
      children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile
      was investigated. The frequency of T (CD3(+), CD4(+), CD8(+)) and B (CD19(+))
      lymphocytes, natural killer (NK) (CD16(+) 56(+)) and regulatory T (T(reg))
      [CD4(+) CD25(+high) forkhead box protein 3 (FoxP3)(+) ] cells was investigated by
      flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy
      controls. Plasma levels of Th1 cytokines [interferon (IFN-gamma) and tumour
      necrosis factor (TNF-alpha)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)]
      cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The
      percentage of Treg (P < 0.001) and natural killer (NK) (P < 0.001) cells were
      significantly decreased in ITP patients compared to healthy controls. A negative
      correlation was reported between the percentage of T(reg) cells and development
      of acute (r = -0.737; P < 0.01) and chronic (r = -0.515; P < 0.01) disease. All
      evaluated cytokines (IFN-gamma, TNF-alpha, IL-4, IL-6 and IL-10) were elevated
      significantly in ITP patients (P < 0.001, P < 0.05, P < 0.05, P < 0.05 and P <
      0.001, respectively) compared to controls. In conclusion, our data shed some
      light on the fundamental role of immune cells and their related cytokines in ITP
      patients. The loss of tolerance in ITP may contribute to the dysfunction of
      T(regs). Understanding the role of T cell subsets will permit a better control of
      autoimmunity through manipulation of their cytokine network.

PMID- 24460859
TI  - Association between erectile dysfunction and echocardiographic variables of
      ventricular hypertrophy and diastolic function in hypertensive patients with type
      2 diabetes mellitus: a cross-sectional study.
AB  - BACKGROUND: This study was conducted among individuals with diabetes and
      hypertension in order to assess the prevalence of erectile dysfunction (ED) and
      the association between ED and cardiovascular risk variables such as
      echocardiographic changes. METHODS: We evaluated 114 men with type 2 diabetes
      mellitus and hypertension. ED was assessed by International Index of Erectile
      Function (IIEF-5) score. Clinical and laboratory variables were evaluated,
      including C-reactive protein (CRP), ambulatory blood pressure monitoring (ABPM),
      ankle brachial index (ABI) and transthoracic echocardiography. Comparisons
      between patients with ED (IIEF-5 < 22) and without ED (IIEF-5 >= 22) were
      performed. RESULTS: Patients were 56.8 +/- 5.7 years-old, systolic and diastolic
      blood pressure were 150.7 +/- 19.5 mmHg and 85.4 +/- 11.4 mmHg, respectively, and
      HbA1c was 8.0 +/- 1.7%. The majority (74.6%) of patients had ED. Levels of CRP,
      ABPM values and ABI were similar between men with and without ED.
      Echocardiography variables related to cardiac chamber diameters, left ventricular
      hypertrophy and diastolic function were similar between groups, except there was
      a slight lower left ventricular ejection fraction in men with ED (64.9 +/- 7.3 vs
      68.1 +/- 3.9%, P = 0.004). CONCLUSIONS: In high cardiovascular risk hypertensive
      individuals with type 2 diabetes, ED is highly prevalent as expected, but its
      presence is associated with neither echocardiographic variables, nor other
      cardiovascular risk factors.

PMID- 24460858
TI  - A longitudinal analysis of patient satisfaction with care and quality of life in
      ambulatory oncology based on the OUT-PATSAT35 questionnaire.
AB  - BACKGROUND: In the oncology setting, there has been increasing interest in
      evaluating treatment outcomes in terms of quality of life and patient
      satisfaction. The aim of our study was to investigate the determinants of patient
      satisfaction, especially the relationship between quality of life and
      satisfaction with care and their changes over time, in curative treatment of
      cancer outpatients. METHODS: Patients undergoing ambulatory chemotherapy or
      radiotherapy in two centers in France were invited to complete the OUT-PATSAT35,
      at the beginning of treatment, at the end of treatment, and three months after
      treatment. This questionnaire evaluates patients' perception of doctors and
      nurses, as well as other aspects of care organization and services. Additionally,
      for each patient, socio-demographic and clinical characteristics, and self
      reported quality of life data (EORTC QLQ-C30) were collected. RESULTS: Of the 691
      patients initially included, 561 answered the assessment at all three time
      points. By cross-sectional analysis, at the end of the treatment, patients who
      experienced a deterioration of their global health reported less satisfaction on
      most scales (p <= 0.001). Three months after treatment, the same patients had
      lower satisfaction scores only in the evaluation of doctors (p <= 0.002).
      Furthermore, longitudinal analysis showed a significant relationship between a
      deterioration in global health and a decrease in satisfaction with their doctor
      and, conversely, between an improvement in global health and an increase in
      satisfaction on the overall satisfaction scale. Global health at baseline was
      largely and significantly associated with all satisfaction scores measured at the
      following assessment time points (p < 0.0001). Younger age (<55 years),
      radiotherapy (versus chemotherapy) and head and neck cancer (versus other
      localizations) were clinical factors significantly associated with less
      satisfaction on most scales evaluating doctors. CONCLUSIONS: Pre-treatment self
      evaluated global health was found to be the major determinant of patient
      satisfaction with care. The subsequent deterioration of global health, during and
      after treatment, emphasized the decrease in satisfaction scores, mainly in the
      evaluation of doctors. Early initiatives aimed at improving the delivery of care
      in patients with poor health status should lead to improved perception of the
      quality of care received.

PMID- 24460860
TI  - How estimation of drinking influences alcohol-related consequences across the
      first year of college.
AB  - BACKGROUND: This study examined how well students estimate their overall drinker
      type and the relation between the accuracy of this estimation with alcohol
      related consequences. The study also explored the association between
      psychosocial alcohol variables and underestimation or overestimation of drinker
      type. METHODS: College students (n = 1,895) completed questionnaires at baseline
      (precollege matriculation) assessing self-reported drinker types (SI), protective
      and risky drinking behaviors, drinking expectancies, attitudes, and norms.
      Postbaseline assessment occurred during the fall semester sophomore year and
      included the number and type of alcohol consequences experienced during the
      previous year. Students' SIs were coded as accurate, overestimated, or
      underestimated relative to their empirically derived latent class analytic
      drinker class. The association between drinker type accuracy and consequences and
      membership in the high-risk Multiple and Repeated Consequence group was assessed,
      as was the relationship between the psychosocial alcohol variables and accuracy.
      RESULTS: Eighteen percent of students underestimated and 10% overestimated their
      drinker type. Students who under- or overestimated their drinker type reported
      experiencing more consequences, even after controlling for drinking. Increases in
      positive alcohol expectancies, protective and risky drinking behaviors, and
      descriptive peer norms were positively associated with underestimation of drinker
      type. Only protective and risky drinking behaviors were associated with
      overestimation. CONCLUSIONS: This study underscores the importance of accurate
      estimation of drinker type and the risk of experiencing alcohol consequences.
      Future research and intervention strategies are discussed.

PMID- 24460861
TI  - Role of the vector genome and underlying factor IX mutation in immune responses
      to AAV gene therapy for hemophilia B.
AB  - BACKGROUND: Self-complementary adeno-associated virus (scAAV) vectors have become
      a desirable vector for therapeutic gene transfer due to their ability to produce
      greater levels of transgene than single-stranded AAV (ssAAV). However, recent
      reports have suggested that scAAV vectors are more immunogenic than ssAAV. In
      this study, we investigated the effects of a self-complementary genome during
      gene therapy with a therapeutic protein, human factor IX (hF.IX). METHODS:
      Hemophilia B mice were injected intramuscularly with ss or scAAV1 vectors
      expressing hF.IX. The outcome of gene transfer was assessed, including transgene
      expression as well as antibody and CD8+ T cell responses to hF.IX. RESULTS: Self
      complementary AAV1 vectors induced similar antibody responses (which eliminated
      systemic hF.IX expression) but stronger CD8+ T cell responses to hF.IX relative
      to ssAAV1 in mice with F9 gene deletion. As a result, hF.IX-expressing muscle
      fibers were effectively eliminated in scAAV-treated mice. In contrast, mice with
      F9 nonsense mutation (late stop codon) lacked antibody or T cell responses, thus
      showing long-term expression regardless of the vector genome. CONCLUSIONS: The
      nature of the AAV genome can impact the CD8+ T cell response to the therapeutic
      transgene product. In mice with endogenous hF.IX expression, however, this
      enhanced immunogenicity did not break tolerance to hF.IX, suggesting that the
      underlying mutation is a more important risk factor for transgene-specific
      immunity than the molecular form of the AAV genome.

PMID- 24460862
TI  - Nursing students' perceptions of their clinical learning environment in
      placements outside traditional hospital settings.
AB  - AIMS AND OBJECTIVES: To explore students' opinions of the learning environment
      during clinical placement in settings outside traditional hospital settings.
      BACKGROUND: Clinical placement experiences may influence positively on nursing
      students attitudes towards the clinical setting in question. Most studies
      exploring the quality of clinical placements have targeted students' experience
      in hospital settings. The number of studies exploring students' experiences of
      the learning environment in healthcare settings outside of the hospital venue
      does not match the growing importance of such settings in the delivery of health
      care, nor the growing number of nurses needed in these venues. DESIGN: A survey
      design was used. METHOD: The Clinical Learning Environment Inventory was
      administered to two cohorts of undergraduate nursing students (n = 184) after
      clinical placement in mental health care, home care and nursing home care.
      RESULTS: Nursing students' overall contentment with the learning environment was
      quite similar across all three placement areas. Students in mental health care
      had significantly higher scores on the subscale individualisation, and older
      students had significantly higher scores on the total scale. Compared with other
      studies where the Clinical Learning Environment Inventory has been used, the
      students' total scores in this study are similar or higher than scores in studies
      including students from hospital settings. CONCLUSION: Results from this study
      negate the negative views on clinical placements outside the hospital setting,
      especially those related to placements in nursing homes and mental healthcare
      settings. RELEVANCE TO CLINICAL PRACTICE: Students' experience of the learning
      environment during placements in mental health care, home care and nursing homes
      indicates the relevance of clinical education in settings outside the hospital
      setting.

PMID- 24460863
TI  - Fluoxetine in progressive multiple sclerosis (FLUOX-PMS): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Currently available disease-modifying treatments acting by modifying
      the immune response are ineffective in progressive multiple sclerosis (MS), which
      is caused by a widespread axonal degeneration. Mechanisms suspected to be
      involved in this widespread axonal degeneration are reduced axonal energy
      metabolism, axonal glutamate toxicity, and reduced cerebral blood flow.
      Fluoxetine might theoretically reduce axonal degeneration in MS because it
      stimulates energy metabolism through enhancing glycogenolysis, stimulates the
      production of brain-derived neurotrophic factor, and dilates cerebral arterioles.
      The current document presents the protocol of a clinical trial to test the
      hypothesis that fluoxetine slows down the progressive phase of MS.
      METHODS/DESIGN: The FLUOX-PMS trial is a multi-center, randomized, controlled and
      double-blind clinical study. A total of 120 patients with the diagnosis of either
      secondary or primary progressive MS will be treated either by fluoxetine (40 mg
      daily) or placebo for a total period of 108 weeks. The primary endpoint is the
      time to confirmed disease progression defined as either at least a 20% increase
      in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test.
      Secondary endpoints include the Hauser ambulation index, cognitive changes,
      fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical
      coherence tomography. DISCUSSION: The FLUOX-PMS trial will gives us information
      as to whether fluoxetine has neuroprotective effects in patients with progressive
      MS. TRIAL REGISTRATION: Eudra-CT: 2011-003775-11.

PMID- 24460865
TI  - Anxiety and surplus in nursing practice: lessons from Lacan and Bataille.
AB  - It is well established, following Menzies' work, that nursing practice produces
      considerable anxiety. Like Menzies, we bring a psychoanalytic perspective to a
      theorization of anxiety in nursing and do so in order to consider nursing
      practice in the light of psychoanalytic theory, although from a Lacanian
      perspective. We also draw on Bataille's notion of 'surplus'. These concepts
      provide the theoretical framework for a study investigating how some clinical
      nurses are able to remain in clinical practice rather than leave the profession
      or seek work at a distance from the bedside. We conducted focus groups and
      present here an analysis of two fragments of nurses' speech. We found the nurses
      responded from one of two positions. In the first position, the nurses focus on
      doctors, complain about the surplus afforded them, and call for it to be
      eliminated. In this way, the nursing group is similar to other groups, considered
      by Bataille, who also attempt to get rid of a surplus. However, in the second
      position, the nurses stay with the surplus, tolerating it as they nurse the
      patient. This latter position is one where the nurse practises with a focus on
      the patient rather than being distracted by their dispute over the doctor's
      privilege. The importance of this paper is in its illustration of two distinct
      positions from which the nurse can practise: one that is not optimal because the
      nurse is distracted and the other that is more focused on practice, and thus the
      nurse is in a position to provide the best care possible to patients.

PMID- 24460864
TI  - Bacillus thuringiensis subsp. kurstaki HD1 as a factory to synthesize alkali
      labile ChiA74?sp chitinase inclusions, Cry crystals and spores for applied use.
AB  - BACKGROUND: The endochitinase ChiA74 is a soluble secreted enzyme produced by
      Bacillus thuringiensis that synergizes the entomotoxigenecity of Cry proteins
      that accumulate as intracellular crystalline inclusion during sporulation. The
      purpose of this study was to produce alkaline-soluble ChiA74?sp inclusions in B.
      thuringiensis, and to determine its effect on Cry crystal production, sporulation
      and toxicity to an important agronomical insect, Manduca sexta. To this end we
      deleted the secretion signal peptide-coding sequence of chiA74 (i.e. chiA74?sp)
      and expressed it under its native promoter (pEHchiA74?sp) or strong chimeric
      sporulation-dependent cytA-p/STAB-SD promoter (pEBchiA74?sp) in Escherichia coli,
      acrystalliferous B. thuringiensis (4Q7) and B. thuringiensis HD1. RESULTS: Based
      on mRNA analyses, up to ~9-fold increase in expression of chiA74?sp was observed
      using the cytA-p/STAB-SD promoter. ChiA74?sp (~70 kDa) formed intracellular
      inclusions that frequently accumulated at the poles of cells. ChiA74?sp
      inclusions were dissolved in alkali and reducing conditions, similar to Cry
      crystals, and retained its activity in a wide range of pH (5 to 9), but showed a
      drastic reduction (~70%) at pH 10. Chitinase activity of E. coli-pEHchiA74?sp was
      ~150 mU/mL, and in E. coli-pEBchiA74?sp, 250 mU/mL. 4Q7-pEBchiA74?sp and 4Q7
      pEHchiA74?sp had activities of ~127 mU/mL and ~41 mU/mL, respectively. The
      endochitinase activity in HD1-pEBchiA74?sp increased 42x when compared to
      parental HD1 strain. HD1-pEBchiA74?sp and HD1 harbored typical bipyramidal Cry
      inclusions, but crystals in the recombinant were ~30% smaller. Additionally, a 3x
      increase in the number of viable spores was observed in cultures of the
      recombinant strain when compared to HD1. Bioassays against first instar larvae of
      M. sexta with spore-crystals of HD1 or spore-crystal-ChiA74?sp inclusions of HD1
      pEBchiA74?sp showed LC50s of 67.30 ng/cm2 and 41.45 ng/cm2, respectively.
      CONCLUSIONS: Alkali-labile ChiA74?sp inclusion bodies can be synthesized in E.
      coli and B. thuringiensis strains. We demonstrated for the first time the applied
      utility of synthesis of ChiA74?sp inclusions, Cry crystals and spores in the same
      sporangium of HD1, a strain used successfully worldwide to control economically
      significant lepidopteran pests of agriculture. Our findings will allow to us
      develop strategies to modify expression of ChiA74?sp while maximizing Cry crystal
      synthesis in commercial strains of B. thuringiensis.

PMID- 24460866
TI  - Comorbidities, confounders, and the white matter transcriptome in chronic
      alcoholism.
AB  - BACKGROUND: Alcohol abuse is the world's third leading cause of disease and
      disability, and one potential sequel of chronic abuse is alcohol-related brain
      damage (ARBD). This clinically manifests as cognitive dysfunction and
      pathologically as atrophy of white matter (WM) in particular. The mechanism
      linking chronic alcohol intoxication with ARBD remains largely unknown but it is
      also complicated by common comorbidities such as liver damage and nutritional
      deficiencies. Liver cirrhosis, in particular, often leads to hepatic
      encephalopathy (HE), a primary glial disease. METHODS: In a novel transcriptomic
      study, we targeted the WM only of chronic alcoholics in an attempt to tease apart
      the pathogenesis of ARBD. Specifically, in alcoholics with and without HE, we
      explored both the prefrontal and primary motor cortices, 2 regions that
      experience differential levels of neuronal loss. RESULTS: Our results suggest
      that HE, along with 2 confounders, gray matter contamination, and low RNA quality
      are major drivers of gene expression in ARBD. All 3 exceeded the effects of
      alcohol itself. In particular, low-quality RNA samples were characterized by an
      up-regulation of translation machinery, while HE was associated with a down
      regulation of mitochondrial energy metabolism pathways. CONCLUSIONS: The findings
      in HE alcoholics are consistent with the metabolic acidosis seen in this
      condition. In contrast non-HE alcoholics had widespread but only subtle changes
      in gene expression in their WM. Notwithstanding the latter result, this study
      demonstrates that significant confounders in transcriptomic studies of human
      postmortem brain tissue can be identified, quantified, and "removed" to reveal
      disease-specific signals.

PMID- 24460867
TI  - Extensive projections of myenteric serotonergic neurons suggest they comprise the
      central processing unit in the colon.
AB  - BACKGROUND: 5-Hydroxytryptamine (5-HT, serotonin) is an important regulator of
      colonic motility and secretion; yet the role of serotonergic neurons in the colon
      is controversial. METHODS: We used immunohistochemical techniques to examine
      their projections throughout the enteric nervous system and interstitial cells of
      Cajal (ICC) networks in the murine proximal to mid colon. KEY RESULTS:
      Serotonergic neurons, which were mainly calbindin positive, occurred only in
      myenteric ganglia (1 per 3 ganglia). They were larger than nNOS neurons but
      similar in size to Dogiel Type II (AH) neurons. 5-HT neurons, appeared to make
      numerous varicose contacts with each other, most nNOS neurons, Dogiel Type II/AH
      neurons and glial cells. 5-HT, calbindin and nNOS nerve fibers also formed a thin
      perimuscular nerve plexus that was associated with ganglia, which contained both
      nNOS positive and negative neurons, which lay directly upon the submucosal
      pacemaker ICC network. Neurons in perimuscular ganglia were surrounded by 5-HT
      varicosities. Submucous ganglia contained nNOS positive and negative neurons, and
      calbindin positive neurons, which also appeared richly supplied by serotonergic
      nerve varicosities. Serotonergic nerve fibers ran along submucosal arterioles,
      but not veins. Varicosities of serotonergic nerve fibers were closely associated
      with pacemaker ICC networks and with intramuscular ICC (ICC-IM). 5-HT2B receptors
      were found on a subpopulation of non-5-HT containing myenteric neurons and their
      varicosities, pacemaker ICC-MY and ICC-IM. CONCLUSIONS & INFERENCES: Myenteric
      serotonergic neurons, whose axons exhibit considerable divergence, regulate the
      entire enteric nervous system and are important in coordinating motility with
      secretion. They are not just interneurons, as regularly assumed, but possibly
      also motor neurons to ICC and blood vessels, and some may even be sensory
      neurons.

PMID- 24460870
TI  - Jackhammer esophagus: high-resolution manometry and therapeutic approach using
      peroral endoscopic myotomy (POEM).
AB  - We present the first report on peroral endoscopic myotomy (POEM) in the treatment
      of jackhammer esophagus. A 34-year-old female patient was newly diagnosed with a
      jackhammer esophagus. After failure of medical treatment, the patient underwent
      POEM procedure for myotomy of the spastic segment. Postoperatively, a mild
      emphysema and pneumothorax occurred that required drainage and antibiotic therapy
      until full recovery. Discharge was possible after 5 days. Six months later, she
      presented with recurrent but mild pain due to a remnant spastic segment proximal
      to the myotomy. Endoscopic balloon dilation was performed twice within 6 weeks
      with full symptomatic relief of pain and mild symptoms of dysphagia. 

PMID- 24460868
TI  - Autoimmune haematological disorders in two Italian children with Kabuki syndrome.
AB  - Kabuki syndrome (also called Niikawa-Kuroki syndrome) is a rare genetic disease
      described for the first time in Japan, characterised by anomalies in multiple
      organ systems and often associated with autoimmune disorders and impaired immune
      response. We herein report the clinical history, the therapeutic approach and the
      outcome of two children with Kabuki syndrome who developed autoimmune
      haematological disorders (haemolytic anaemia and immune thrombocytopenia).
      Factors regarding differential diagnosis and interventions in better management
      of this syndrome and its complications are discussed. This is the first report of
      Italian children with autoimmune haematological disorders complicating Kabuki
      syndrome.

PMID- 24460869
TI  - Extracellular matrix remodeling following myocardial infarction influences the
      therapeutic potential of mesenchymal stem cells.
AB  - INTRODUCTION: Although stem cell therapy is a promising treatment for myocardial
      infarction, the minimal functional improvements observed clinically limit its
      widespread application. A need exists to maximize the therapeutic potential of
      these stem cells by first understanding what factors within the infarct
      microenvironment affect their ability to regenerate the necrotic tissue. In this
      study, we assessed both differentiation capacity and paracrine signaling as a
      function of extracellular matrix remodeling after myocardial infarction. METHODS:
      Mechanical and compositional changes to the decellularized infarcted myocardium
      were characterized to understand how the extracellular environment, specifically,
      was altered as a function of time after coronary artery ligation in Sprague
      Dawley rats. These alterations were first modeled in a polyacrylamide gel system
      to understand how the variables of composition and stiffness drive mesenchymal
      stem cell differentiation towards a cardiac lineage. Finally, the paracrine
      secretome was characterized as a function of matrix remodeling through gene and
      protein expression and conditioned media studies. RESULTS: The decellularized
      infarct tissue revealed significant alterations in both the mechanical and
      compositional properties of the ECM with remodeling following infarction. This
      altered microenvironment dynamically regulates the potential for early cardiac
      differentiation. Whereas Nkx2.5 expression is limited in the presence of chronic
      remodeled matrix of increased stiffness, GATA4 expression is enhanced. In
      addition, the remodeled matrix promotes the expression of several proangiogenic,
      prosurvival, antifibrotic, and immunomodulatory growth factors. In particular, an
      increase in HGF and SDF1 expression and secretion by mesenchymal stem cells can
      rescue oxidatively stressed cardiomyocytes in vitro. CONCLUSIONS: This study
      demonstrated that decellularization of diseased tissue allows for the exclusive
      analysis of the remodeled matrix and its ability to influence significantly the
      cellular phenotype. Characterization of cell fate as a function of myocardial
      remodeling following infarction is critical in developing the ideal strategy for
      cell implantation to maximize tissue regeneration and to ultimately reduce the
      prevalence and severity of heart failure.

PMID- 24460872
TI  - Kinase inhibitors: the next generation of therapies in the treatment of
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) can be the source of significant pain and functional
      limitation. The past 20 years have seen a transition in treatment goals away from
      mere pain management toward disease modification through the suppression of
      autoimmunity. Disease-modifying anti-rheumatic drugs, such as methotrexate and
      biologic agents, impair disease progression and joint destruction. However,
      despite these achievements, a substantial subset of RA patients does not respond
      to or cannot tolerate current treatments for RA. Scientific insight into the
      cellular pathways of inflammation has revealed new therapeutic targets for the
      treatment of autoimmune diseases like RA. Attention has focused on pathways
      mediated by Janus kinase (JAK), mitogen-activated protein kinase (MAPK), and
      spleen tyrosine kinase (Syk). This review article summarizes the evidence
      supporting the use of various kinase inhibitors, including the newly approved JAK
      inhibitor tofacitinib, in the treatment of RA.

PMID- 24460871
TI  - From cheek swabs to consensus sequences: an A to Z protocol for high-throughput
      DNA sequencing of complete human mitochondrial genomes.
AB  - BACKGROUND: Next-generation DNA sequencing (NGS) technologies have made huge
      impacts in many fields of biological research, but especially in evolutionary
      biology. One area where NGS has shown potential is for high-throughput sequencing
      of complete mtDNA genomes (of humans and other animals). Despite the increasing
      use of NGS technologies and a better appreciation of their importance in
      answering biological questions, there remain significant obstacles to the
      successful implementation of NGS-based projects, especially for new users.
      RESULTS: Here we present an 'A to Z' protocol for obtaining complete human
      mitochondrial (mtDNA) genomes - from DNA extraction to consensus sequence.
      Although designed for use on humans, this protocol could also be used to sequence
      small, organellar genomes from other species, and also nuclear loci. This
      protocol includes DNA extraction, PCR amplification, fragmentation of PCR
      products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a
      complete bioinformatics pipeline (primer removal, reference-based mapping, output
      of coverage plots and SNP calling). CONCLUSIONS: All steps in this protocol are
      designed to be straightforward to implement, especially for researchers who are
      undertaking next-generation sequencing for the first time. The molecular steps
      are scalable to large numbers (hundreds) of individuals and all steps post-DNA
      extraction can be carried out in 96-well plate format. Also, the protocol has
      been assembled so that individual 'modules' can be swapped out to suit available
      resources.

PMID- 24460874
TI  - The vexed question of hypoglycaemia and health economics.

PMID- 24460873
TI  - Thrombospondins 1 and 2 are important for afferent synapse formation and function
      in the inner ear.
AB  - Thrombospondins (TSPs) constitute a family of secreted extracellular matrix
      proteins that have been shown to be involved in the formation of synapses in the
      central nervous system. In this study, we show that TSP1 and TSP2 are expressed
      in the cochlea, and offer the first description of their putative roles in
      afferent synapse development and function in the inner ear. We examined mice with
      deletions of TSP1, TSP2 and both (TSP1/TSP2) for inner ear development and
      function. Immunostaining for synaptic markers indicated a significant decrease in
      the number of formed afferent synapses in the cochleae of TSP2 and TSP1/TSP2
      knockout (KO) mice at postnatal day (P)29. In functional studies, TSP2 and
      TSP1/TSP2 KO mice showed elevated auditory brainstem response (ABR) thresholds as
      compared with wild-type littermates, starting at P15, with the most severe
      phenotype being seen for TSP1/TSP2 KO mice. TSP1/TSP2 KO mice also showed reduced
      wave I amplitudes of ABRs and vestibular evoked potentials, suggesting synaptic
      dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds
      in TSP1 KO mice were relatively unaffected at early ages, TSP1/TSP2 KO mice
      showed the most severe phenotype among all of the genotypes tested, suggesting
      functional redundancy between the two genes. On the basis of the above results,
      we propose that TSPs play an important role in afferent synapse development and
      function of the inner ear. 

PMID- 24460875
TI  - Gamma-aminobutyric acid system genes--no evidence for a role in alcohol use and
      abuse in a community-based sample.
AB  - BACKGROUND: While twin and adoption studies point to substantial genetic
      influence upon alcohol use, dependence, and other alcohol-related phenotypes, few
      of the genes underlying variation in these phenotypes have been identified.
      Markers in genes related to GABAergic activity-a system integral to many of
      alcohol's biological effects-have been implicated in alcohol use and alcohol
      related psychopathology in linkage and association studies. METHODS: Using
      multiple methods, we conducted a comprehensive examination of the effects of
      markers in gamma-aminobutyric acid (GABA) system genes in a community-based
      sample of 7,224 individuals assessed in early and middle adulthood. In addition
      to testing the effect of individual single nucleotide polymorphism (SNP) markers
      on alcohol-related phenotypes, we computed a polygenic score reflecting the
      aggregated effects of multiple GABA system SNPs. We also estimated the variance
      in alcohol-related phenotypes attributable to all GABA system markers considered
      simultaneously and conducted gene-based association tests. RESULTS: No method
      produced results indicative of an effect of GABA system variants on measures of
      alcohol use or misuse. CONCLUSIONS: These results reflect alcohol-related
      behaviors in a population-representative sample, many of whom are still in
      adolescence, and in which the incidence of heavy drinking and alcohol-related
      symptomatology are relatively low. Contrasted with existing studies of the
      association between alcohol use and GABA system genes, our results suggest that
      the relationship may be limited to particular contexts, such as when accompanied
      by polysubstance abuse or a familial history of alcoholism.

PMID- 24460876
TI  - Microbial and chemical composition of liquid-associated bacteria in goats' rumen
      and fermenters.
AB  - This study was undertaken to investigate the relationship between chemical
      composition and microbial profile of rumen liquid-associated bacteria (LAB) in
      vivo (Murciano-Granadina goats) and in a rumen simulation system (single-flow
      continuous-culture fermenters). To achieve this aim, analyses of purine bases
      along with some molecular techniques (quantitative PCR to assess abundance and
      DGGE to identify biodiversity and bacterial profile) were carried out. A control
      diet (AHC) based on alfalfa hay (AH) and concentrate (C) in a 1:1 ratio and two
      experimental diets (AHCBI and AHCBII), in which concentrate was partially
      replaced with multinutrient blocks, were used. Diets AHCBI and AHCBII included
      multinutrient blocks differing in the relative amount of two-stage olive cake and
      the source of protein (sunflower meal vs. fava beans). We aimed to investigate
      the effect of these blocks on rumen microbiota to evaluate their potential as
      safe substitutes of cereal-based concentrates. Similar patterns of response to
      diet were found for chemical composition, microbial abundances and diversity in
      LAB isolated from goat's rumen and fermenters. Whereas bacterial density (log10
      gene copies/g FM: 11.6 and 9.4 for bacteria and methanogens, respectively, in
      rumen) and diversity indexes (Shannon index: 3.6) were not affected by diet, DGGE
      analyses showed that bacterial community profile was affected. The cluster
      analysis suggested differences in bacterial profile between LAB pellets isolated
      from the rumen of goat and fermenters. A relationship between chemical
      composition and bacterial community composition in LAB pellets seems to exist.
      Changes in the former were reflected in the bacterial community profile. Further
      research is needed to clarify the relationship between chemical and microbial
      composition of ruminal bacterial pellets with diets of different quality. 

PMID- 24460877
TI  - In vivo characterization of the role of tissue-specific translation elongation
      factor 1A2 in protein synthesis reveals insights into muscle atrophy.
AB  - Translation elongation factor 1A2 (eEF1A2), uniquely among translation factors,
      is expressed specifically in neurons and muscle. eEF1A2-null mutant wasted mice
      develop an aggressive, early-onset form of neurodegeneration, but it is unknown
      whether the wasting results from denervation of the muscles, or whether the mice
      have a primary myopathy resulting from loss of translation activity in muscle. We
      set out to establish the relative contributions of loss of eEF1A2 in the
      different tissues to this postnatal lethal phenotype. We used tissue-specific
      transgenesis to show that correction of eEF1A2 levels in muscle fails to
      ameliorate the overt phenotypic abnormalities or time of death of wasted mice.
      Molecular markers of muscle atrophy such as Fbxo32 were dramatically upregulated
      at the RNA level in wasted mice, both in the presence and in the absence of
      muscle-specific expression of eEF1A2, but the degree of upregulation at the
      protein level was significantly lower in those wasted mice without transgene
      derived expression of eEF1A2 in muscle. This provides the first in vivo
      confirmation that eEF1A2 plays an important role in translation. In spite of the
      inability of the nontransgenic wasted mice to upregulate key atrogenes at the
      protein level in response to denervation to the same degree as their transgenic
      counterparts, there were no measurable differences between transgenic and
      nontransgenic wasted mice in terms of weight loss, grip strength, or muscle
      pathology. This suggests that a compromised ability fully to execute the atrogene
      pathway in denervated muscle does not affect the process of muscle atrophy in the
      short term.

PMID- 24460878
TI  - Are parents' knowledge and practice regarding immunization related to pediatrics'
      immunization compliance? a mixed method study.
AB  - BACKGROUND: Immunization rate is one of the best public health outcome and
      service indicators of the last 100 years. Parental decisions regarding
      immunization are very important to improve immunization rate. The aim of this
      study was to evaluate the correlation between parental knowledge-practices (KP)
      and children's immunization completeness. METHODS: A mixed method has been
      utilized in this study: a retrospective cohort study was used to evaluate
      immunization completeness; a prospective cross-sectional study was used to
      evaluate immunization KP of parents. 528 children born between 1 January 2003 and
      31 June 2008 were randomly selected from five public health clinics in Mosul,
      Iraq. Immunization history of each child was collected retrospectively from their
      immunization record/card. RESULTS: About half of studied children (n = 286,
      56.3%) were immunized with all vaccination doses; these children were considered
      as having had complete immunization. 66.1% of the parents was found to have
      adequate KP scores. A significant association of immunization completeness with
      total KP groups (p < 0.05) was found. CONCLUSIONS: Future efforts are required to
      improve immunization rate and parents' knowledge and practice. The study results
      reinforce recommendations for the periodic assessment of immunization rate and
      the use of educational programmes to improve the immunization rate, knowledge and
      practice.

PMID- 24460880
TI  - Lightning strikes thrice.

PMID- 24460879
TI  - Bilateral cauliflower ear as the presenting sign of B-cell chronic lymphocytic
      leukemia.

PMID- 24460881
TI  - Dermatopathology by the numbers.

PMID- 24460883
TI  - Effective notification of important non-urgent radiology results: a qualitative
      study of challenges and potential solutions.
AB  - INTRODUCTION: We report on the implementation of a Radiology Notification System
      (RNS), set up by the medical imaging department of a major Sydney teaching
      hospital in March 2010. This study aimed to investigate the views of the medical
      imaging department staff about: (i) the results follow-up problem encountered by
      the medical imaging department prior to the implementation of the RNS; (ii) what
      changes occurred following implementation of the RNS; and (iii) suggestions for
      improving the RNS. METHODS: This is a cross-sectional qualitative study
      incorporating semi-structured interviews with 16 staff (15 radiologists and 1
      clerk) after the implementation of the RNS. Interviews were conducted in
      August/September 2011. RESULTS: The reasons behind the development of the RNS
      were related to: (i) major existing problems with the communication of results
      between the imaging department and hospital wards; (ii) cumbersome and
      inefficient paper-based notification systems; and (iii) the absence of
      standardised guidelines and procedures for radiology test notification and follow
      up. The RNS managed to free up a significant proportion of radiologist time,
      resulting in greater efficiencies. Study participants also highlighted a number
      of areas for improvement, including the need for a 24-h service, feedback and
      acknowledgement of test results by clinicians and the standardisation of test
      management definitions and procedures. CONCLUSION: Test management systems can
      play an important part in enhancing safe and effective communications between
      wards and hospital departments. However, their uptake and sustainability will
      require the establishment of a multidisciplinary and hospital-wide collaboration
      that includes clinicians.

PMID- 24460884
TI  - Bolus retention in hiatal hernia identified by high-resolution esophageal
      manometry with impedance.
AB  - BACKGROUND: Esophageal acid retention in a hiatal hernia (HH) may play a role in
      gastro-esophageal reflux. The aims of this study were to determine the prevalence
      of bolus retention (BR) in HH and to compare pressure profiles in patients with
      HH with BR in the hernia to those with bolus clearance (BC) through the hernia
      using high-resolution esophageal manometry with impedance (HREMI). METHODS:
      Clinical HREMI studies with HH >=1.5 cm were analyzed for lower esophageal
      sphincter (LES) and crural diaphragm (CD) pressures and pressure profiles during
      12 saline swallows. Impedance was analyzed for swallow retention in the HH. KEY
      RESULTS: Bolus retention in a HH was present in 35 of 53 (66%) patients with a
      HH. Patients with BR had overall lower pressure profiles including a lower basal
      LES pressure (14.8 +/- 10.6 vs 28.9 +/- 16.8 mmHg; p = 0.0001), LES-CD gradient
      (6.8 +/- 17.9 vs 20.6 +/- 12.2 mmHg; p = 0.002), residual LES pressure (2.5 +/-
      4.6 vs 6.1 +/- 12.2 mmHg; p = 0.017), amplitude of distal esophageal contractions
      (83.2 +/- 38.8 vs 111.2 +/- 42.8 mmHg; p = 0.020), and distal contractile
      integral (1487 +/- 1016 vs 2608 +/- 1221 mmHg-cm-sec; p = 0.001) compared to the
      BC group. Patients with BR were more likely to have a larger sized HH compared to
      the BC group (3.1 +/- 1.6 vs 2.1 +/- 0.6 cm; p = 0.016); similar pressure changes
      were found when the groups were divided up by HH sizes. CONCLUSIONS & INFERENCES:
      Bolus retention was seen in 66% of patients with HH. Bolus retention in the HH
      was associated with larger HH size, lower LES pressure, and lower esophageal
      contractile pressures compared to those with BC.

PMID- 24460885
TI  - Feasibility and clinical outcomes when using practice guidelines for evaluation
      of fever in returning travelers and migrants: a validation study.
AB  - BACKGROUND: Practice guidelines for examining febrile patients presenting upon
      returning from the tropics were developed to assist primary care physicians in
      decision making. Because of the low level of evidence available in this field,
      there was a need to validate them and assess their feasibility in the context
      they have been designed for. OBJECTIVES: The objectives of the study were to (1)
      evaluate physicians' adherence to recommendations; (2) investigate reasons for
      non-adherence; and (3) ensure good clinical outcome of patients, the ultimate
      goal being to improve the quality of the guidelines, in particular to tailor them
      for the needs of the target audience and population. METHODS: Physicians
      consulting the guidelines on the Internet (www.fevertravel.ch) were invited to
      participate in the study. Navigation through the decision chart was automatically
      recorded, including diagnostic tests performed, initial and final diagnoses, and
      clinical outcomes. The reasons for non-adherence were investigated and
      qualitative feedback was collected. RESULTS: A total of 539 physician/patient
      pairs were included in this study. Full adherence to guidelines was observed in
      29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for
      non-adherence were as follows: no repetition of malaria tests (111/352) and no
      presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain
      without leukocytosis (46/101). Overall, 20% of diversions from guidelines were
      considered reasonable because there was an alternative presumptive diagnosis or
      the symptoms were mild, which means that the corrected adherence rate per case
      was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and
      all complications could be attributed to the underlying illness rather than to
      adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible,
      useful, and leading to good clinical outcomes. Almost one third of physicians
      strictly adhered to the guidelines. Other physicians used the guidelines not to
      forget specific diagnoses but finally diverged from the proposed attitudes. These
      diversions should be scrutinized for further refinement of the guidelines to
      better fit to physician and patient needs.

PMID- 24460886
TI  - Farewell.

PMID- 24460887
TI  - Increased serum CXCL16 is highly correlated with blood lipids, urine protein and
      immune reaction in children with active nephrotic syndrome.
AB  - BACKGROUND: Primary nephrotic syndrome (NS) is a common disease in children.
      Lipid nephrotoxicity and cellular immune dysfunction are known features of this
      disease. Recently, CXCL16 was found to participate in inflammation and mediate
      cellular uptake of lipids. Here, we investigated the involvement of CXCL16 in the
      occurrence and development of primary NS. METHODS: Serum CXCL16, blood lipids and
      albumin, 24-hour urine protein, interferon-gamma and immune cells were detected
      in 25 children with steroid sensitive NS during their active nephrotic and
      remissive stages. Twenty healthy children served as the control group. RESULTS:
      Levels of serum CXCL16, blood lipids, interferon-gamma and CXCR6+ T cells were
      significantly increased and albumin and NK cell number were significantly
      decreased in the active status group compared with remissive status and control
      groups. Correlation analysis showed that serum CXCL16 was positively correlated
      with blood lipids, 24-hour urine protein, interferon-gamma and CXCR6+ T cells but
      negatively correlated with albumin in patients with active NS. CONCLUSION: Serum
      CXCL16 was increased in patients with active NS and correlated with blood lipids,
      urine protein and immune and inflammation responses, suggesting that CXCL16 may
      serve as a useful index or biomarker for disease activity in children with
      nephrotic syndrome. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1120468411154766.

PMID- 24460888
TI  - Strategic patent analysis in plant biotechnology: terpenoid indole alkaloid
      metabolic engineering as a case study.
AB  - The do-it-yourself patent search is a useful alternative to professional patent
      analysis particularly in the context of publicly funded projects where funds for
      IP activities may be limited. As a case study, we analysed patents related to the
      engineering of terpenoid indole alkaloid (TIA) metabolism in plants. We developed
      a focused search strategy to remove redundancy and reduce the workload without
      missing important and relevant patents. This resulted in the identification of
      approximately 50 key patents associated with TIA metabolic engineering in plants,
      which could form the basis of a more detailed freedom-to-operate analysis. The
      structural elements of this search strategy could easily be transferred to other
      contexts, making it a useful generic model for publicly funded research projects.

PMID- 24460889
TI  - Regulatory options for genetically modified crops in India.
AB  - The introduction of semi-dwarfing, high-yielding and nutrients-responsive crop
      varieties in the 1960s and 1970s alleviated the suffering of low crop yield, food
      shortages and epidemics of famine in India and other parts of the Asian
      continent. Two semi-dwarfing genes, Rht in wheat and Sd-1 in rice heralded the
      green revolution for which Dr. Norman Borlaug was awarded the Nobel Peace Prize
      in 1970. In contrast, the revolutionary new genetics of crop improvement shamble
      over formidable obstacles of regulatory delays, political interferences and
      public misconceptions. India benefited immensely from the green revolution and is
      now grappling to deal with the nuances of GM crops. The development of GM mustard
      discontinued prematurely in 2001 and insect-resistant Bt cotton varieties were
      successfully approved for commercial cultivation in 2002 in an evolving nature of
      regulatory system. However, the moratorium on Bt brinjal by MOEF in 2010 meant a
      considerable detour from an objective, science-based, rigorous institutional
      process of regulatory approval to a more subjective, nonscience-driven, political
      decision-making process. This study examines what ails the regulatory system of
      GM crops in India and the steps that led to the regulatory logjam. Responding to
      the growing challenges and impediments of existing biosafety regulation, it
      suggests options that are critical for GM crops to take roots for a multiplier
      harvest. 

PMID- 24460890
TI  - Genomewide discovery of DNA polymorphisms in rice cultivars with contrasting
      drought and salinity stress response and their functional relevance.
AB  - Next-generation sequencing technologies provide opportunities to understand the
      genetic basis of phenotypic differences, such as abiotic stress response, even in
      the closely related cultivars via identification of large number of DNA
      polymorphisms. We performed whole-genome resequencing of three rice cultivars
      with contrasting responses to drought and salinity stress (sensitive IR64,
      drought-tolerant Nagina 22 and salinity-tolerant Pokkali). More than 356 million
      90-bp paired-end reads were generated, which provided about 85% coverage of the
      rice genome. Applying stringent parameters, we identified a total of 1 784 583
      nonredundant single-nucleotide polymorphisms (SNPs) and 154 275 InDels between
      reference (Nipponbare) and the three resequenced cultivars. We detected 401 683
      and 662 509 SNPs between IR64 and Pokkali, and IR64 and N22 cultivars,
      respectively. The distribution of DNA polymorphisms was found to be uneven across
      and within the rice chromosomes. One-fourth of the SNPs and InDels were detected
      in genic regions, and about 3.5% of the total SNPs resulted in nonsynonymous
      changes. Large-effect SNPs and InDels, which affect the integrity of the encoded
      protein, were also identified. Further, we identified DNA polymorphisms present
      in the differentially expressed genes within the known quantitative trait loci.
      Among these, a total of 548 SNPs in 232 genes, located in the conserved
      functional domains, were identified. The data presented in this study provide
      functional markers and promising target genes for salinity and drought tolerance
      and present a valuable resource for high-throughput genotyping and molecular
      breeding for abiotic stress traits in rice.

PMID- 24460891
TI  - Ventricular oversensing after ICD lead replacement: what is the mechanism?

PMID- 24460892
TI  - Human ethmoid sinus mucosa: a promising novel tissue source of mesenchymal
      progenitor cells.
AB  - INTRODUCTION: The identification of new progenitor cell sources is important for
      cell-based tissue engineering strategies, understanding regional tissue
      regeneration, and modulating local microenvironments and immune response.
      However, there are no reports that describe the identification and isolation of
      mesenchymal progenitor cells (MPCs) from paranasal sinus mucosa, and compare the
      properties of MPCs between tissue sources within the sinonasal cavity. We report
      here the identification of MPCs in the maxillary sinus (MS) and ethmoid sinus
      (ES). Furthermore, we contrast these MPCs in the same individuals with MPCs from
      two additional head and neck tissue sources of the inferior turbinate (IT) and
      tonsil (T). METHODS: These four MPC sources were exhaustively compared for
      morphology, colony-forming potential, proliferation capability, immunophenotype,
      multilineage differentiation potential, and ability to produce soluble factors.
      RESULTS: MS-, ES, IT-, and T-MPCs showed similar morphologies and surface
      phenotypes, as well as adipogenic, osteogenic, and chondrogenic differentiation
      capacity by immunohistochemistry and qRT-PCR for defined lineage-specific genes.
      However, we noted that the colony-forming potential and proliferation capability
      of ES-MPCs were distinctly higher than other MPCs. All MPCs constitutively, or
      upon stimulation, secrete large amounts of IL-6, IL-8, IL-10, IFN-gamma, and TGF
      beta. After stimulation with TNF-alpha and IFN-gamma, ES-MPCs notably
      demonstrated significantly higher secretion of IL-6 and IL-10 than other MPCs.
      CONCLUSIONS: ES-MPCs may be a uniquely promising source of MPCs due to their high
      proliferation ability and superior capacity toward secretion of immunomodulatory
      cytokines.

PMID- 24460893
TI  - The value of simple microbiological studies for on-site screening of acute
      neonatal conjunctivitis in Angola.
AB  - BACKGROUND: Neonatal conjunctivitis or ophthalmia neonatorum (ON) is an acute
      bacterial conjunctivitis contracted by newborns during delivery. In non
      industrialized countries, detection of the etiological agent is difficult due to
      the unavailability of modern diagnostic resources. Therefore, we analyzed the
      effectiveness of Gram and methylene blue staining techniques, which are simple
      microbiological methods in suspecting the aetiology of ON in a maternity ward in
      Luanda, Angola. FINDINGS: Neonatal conjunctival smears (n = 95), maternal data,
      and perinatal factors were collected. Slides were air-dried and sent to the
      Microbiology Department of the Hospital Clinico Universitario, Valladolid, Spain,
      where trained personnel performed Gram and methylene blue staining methods.
      Findings were interpreted by two expert microbiologists. Ophthalmological
      examination of all children showed five newborns with clinical signs of ON.
      Fourteen mothers reported were suspected with vulvo-vaginitis, and 27 had a
      urinary infection during pregnancy. Gram staining revealed the presence of
      epithelial cells in 87.6% and leukocytes in 15% of the conjunctival smears. These
      values were significantly higher than those shown by methylene blue staining. No
      rods, cocci, or yeasts were identified by either staining method. Chlamydia
      trachomatis DNA was also undetected in a small sub-sample with clinical suspicion
      of ON. There was no correlation among the presence of ON, ON microbes, maternal
      data, or perinatal factors. CONCLUSIONS: Basic microbiological techniques did not
      provide enough information for screening cases of ON in Angola. Therefore, the
      use of molecular biology or other techniques is warranted for this purpose.

PMID- 24460894
TI  - Dry computational approaches for wet medical problems.
AB  - This is a report on the 4th international conference in 'Quantitative Biology and
      Bioinformatics in Modern Medicine' held in Belfast (UK), 19-20 September 2013.
      The aim of the conference was to bring together leading experts from a variety of
      different areas that are key for Systems Medicine to exchange novel findings and
      promote interdisciplinary ideas and collaborations.

PMID- 24460895
TI  - PTOP and TRF1 help enhance the radio resistance in breast cancer cell.
AB  - PURPOSE: The telomere binding proteins play an important role in telomere
      function, which contribute greatly to the radio resistant in human cancers. This
      research is designed to investigate the relationship among the telomere length,
      telomerase activity and changes of telomere binding protein PTOP and TRF1 in
      radio resistant breast cancer cell lines. METHODS: Irradiate MDA-MB-435 s breast
      cancer cell with total dose of 60 Gy delivered in 2 Gy/fraction and 6 Gy/fraction
      respectively, then measuring their telomere length by Southern blot
      analysis,telomerase activity by Telomerase PCR Elisa and detecting the expression
      of PTOP and TRF1 in both gene and protein levels. To further investigate the
      function of PTOP, using lentivirus technic to silence the PTOP gene and the
      detected the new silenced cells by southern blot and telomerase activity.
      RESULTS: 2 radio resistant breast cancer cell lines were successfully
      established. The MDA-MB-435 s R60/6 was (approximate 8.1-8.6 kbp) about 2-2.4
      folds to the patent cell (3.6-4.2 kbp), the MDA-MB-435 s R60/2 cell (approximate
      5.3-6.3 kbp) was about 1.3-1.75 fold to the parent cell line. The telomerase
      activity was more enhanced in radio resistant cell lines than the parent cell.
      The expression of PTOP and TRF1 were significant increased in radio resistant
      cell lines than the patent cell in both gene and protein level. Otherwise, after
      using lentivirus technic to silence the PTOP gene, we found the radio resistant
      cell lines were significant decrease their radio resistances and telomerase
      activities. CONCLUSION: The telomere binding protein PTOP and TRF1 were increased
      expressed in radio resistant breast cancer cell, PTOP was observed instinct
      positive correlated with telomere lengthen and telomerase activity enhancement.

PMID- 24460896
TI  - The prognostic value of metformin for cancer patients with concurrent diabetes: a
      systematic review and meta-analysis.
AB  - AIM: Emerging evidence from epidemiologic studies and basic science suggests a
      potential antitumour effect of metformin. However, whether metformin improves
      survival in cancer patients remains inconclusive. METHODS: A literature search
      was performed using the PubMed, EMbase and SciVerse Scopus databases. Pooled
      effect estimates were derived using a random-effects meta-analysis model.
      RESULTS: Of the 28 studies retrieved, the pooled effect estimates showed that
      metformin was associated with lower risk of all-cause mortality in cancer
      patients with concurrent diabetes, particularly for breast [pooled relative risk
      (RR) 0.70, 95% CI 0.55, 0.88; p = 0.003], colorectal (RR 0.70, 95% CI 0.59, 0.84;
      p < 0.001), ovarian (RR 0.44, 95% CI 0.30, 0.64; p < 0.001) and endometrial
      cancer (RR 0.49, 95% CI 0.32, 0.73; p = 0.001). In addition, metformin was
      associated with lower risks of cancer-specific mortality. CONCLUSIONS: The
      findings of this study support the hypothesis that metformin improves the
      survival for cancer patients with concurrent diabetes, particularly for breast,
      colorectal, ovarian, and endometrial cancer. Further investigation is warranted.

PMID- 24460897
TI  - Self-reported behaviour problems and sibling relationship quality by siblings of
      children with autism spectrum disorder.
AB  - BACKGROUND: There are few published research studies in which siblings of
      children with autism spectrum disorder (ASD) provide self-reports about their own
      behavioural and emotional problems and their sibling relationships. Reliance on
      parent reports may lead to incomplete conclusions about the experiences of
      siblings themselves. METHODS: Siblings 7-17 years and their mothers from 94
      families of children with ASD were recruited. Mothers reported on family
      demographics, the behavioural and emotional problems of their child with ASD, and
      on their own symptoms of depression. Siblings reported on their relationship with
      their brother or sister with ASD, and siblings 11+ years of age also self
      reported on their behavioural and emotional problems. RESULTS: Compared with
      normative British data, siblings reported very slightly elevated levels of
      behavioural and emotional problems. However, none of the mean differences were
      statistically significant and all group differences were associated with small or
      very small effect sizes - the largest being for peer problems (effect size =
      0.31). Regression analysis was used to explore family systems relationships, with
      sibling self-reports predicted by the behaviour problems scores for the child
      with ASD and by maternal depression. Maternal depression did not emerge as a
      predictor of siblings' self-reported sibling relationships or their behavioural
      and emotional problems. Higher levels of behaviour problems in the child with ASD
      predicted decreased warmth/closeness and increased conflict in the sibling
      relationship. CONCLUSIONS: These data support the general findings of recent
      research in that there was little indication of clinically meaningful elevations
      in behavioural and emotional problems in siblings of children with ASD. Although
      further research replication is required, there was some indication that sibling
      relationships may be at risk where the child with ASD has significant behaviour
      problems.

PMID- 24460899
TI  - Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral
      tissues under physiological conditions.
AB  - The pineal gland secretes melatonin (MLT) that circulates in the blood and
      cerebrospinal fluid (CSF). We provide data to support the hypothesis that, in
      sheep and possibly in humans, only the CSF MLT, and not the blood MLT, can
      provide most of MLT to the cerebral tissue in high concentrations, particularly
      in the periventricular area. The MLT content of sheep brain, our chosen animal
      model, was found in significant concentration gradients oriented from the
      ventricle (close to the CSF) to the cerebral tissue, with concentrations varying
      by a factor of 1-125. The highest concentrations were observed close to the
      ventricle wall, whereas the lowest concentrations were furthest from the
      ventricles (407.0 +/- 71.5 pg/ml compared to 84.7 +/- 5.2 pg/ml around the third
      ventricle). This concentration gradient was measured in brain tissue collected at
      mid-day and at the end of the night. Nocturnal concentrations were higher than
      daytime concentrations, reflecting the diurnal variation in the pineal gland. The
      concentration gradient was not detected when MLT was delivered to the brain via
      the bloodstream. The diffusion of MLT to cerebral tissues via CSF was supported
      by in vivo scintigraphy and autoradiography. 2-[(123)I]-MLT infused into the CSF
      quickly and efficiently diffused into the brain tissues, whereas [(123)I]-iodine
      (control) was mostly washed away by the CSF flow and [(123)I]-bovine serum
      albumin remained mostly in the CSF. Taken together, these data support a critical
      role of CSF in providing the brain with MLT.

PMID- 24460900
TI  - Responses to betaine and inorganic sulphur of sheep in growth performance and
      fibre growth.
AB  - Sulphur-containing amino acids (SAA) are essential and usually the first limiting
      amino acids for growth, milk and wool production. The keratin fibre that grows
      from epidermal tissue is rich in SAA. The rate of fibre growth and its S content
      are influenced by the availability of SAA. Betaine is a dietary source for a
      labile methyl group and actively participates in methionine metabolism by
      donating methyl groups for the remethylation of homocysteine to methionine.
      Ruminants are capable of synthesizing SAA from inorganic S sources, and most
      bacteria in the rumen can use inorganic S to meet their requirements for growth.
      The objective of this study was to examine whether betaine and an inorganic
      sulphur supplement could provide methyl groups and sulphur amino acids in a way
      that growth performance and wool production of ewes and lambs are improved.
      Treatments performed included betaine supplementation, sulphate supplementation
      and betaine plus sulphate supplementation with five replications for each
      treatment. The dry matter intake of the ewes was affected by betaine plus
      sulphate supplementation (p < 0.05). In the ewes, betaine plus sulphate
      supplementation increased (p < 0.05) the wool growth rate, wool yield, staple
      length and wool sulphur concentration, while decreasing wool wax and wool
      yellowness (p < 0.05). In the lambs, wool growth rate, wool yield, fibre
      diameter, staple length, staple strength, wool sulphur concentration, wool wax
      and fibre percentage did not differ (p > 0.05) between treatments. In the ewes,
      plasma methionine concentration increased (p < 0.05) with betaine plus sulphate
      treatment. No corresponding difference (p > 0.05) was observed in plasma
      methionine concentration in the lambs. It can be concluded that betaine plus
      sulphate supplementation has the potential to change wool characteristics in the
      ewes, while these compounds were without any effect on growth and wool production
      of the lambs. Combining the two supplements was advantageous.

PMID- 24460901
TI  - Ethanol induces conditioned social preference in male mice.
AB  - BACKGROUND: Affiliative social interactions promote alcohol consumption, and
      alcohol also promotes affiliative behavior. Furthermore, for most species,
      moderate doses of ethanol (EtOH) and social affiliation are each rewarding.
      However, animal studies of drug and EtOH reward typically test individuals in
      isolation. To address social dimensions of EtOH reward, this study tested EtOH
      induced conditioned social preference in male C57BL/6 mice with (ORCHX+T) and
      without (ORCHX) testosterone. METHODS: ORCHX+T males received EtOH (0, 1, 2, or 3
      g/kg) intraperitoneally and were paired 4* for 30 minutes each with 1 of 2
      stimulus males: with the CS- stimulus male after saline injection and with the
      CS+ male following EtOH. After pairing, time spent with CS+ and CS- males was
      measured in a 10-minute test. RESULTS: ORCHX+T test males showed conditioned
      preference for the CS+ male in response to 3 g/kg EtOH (change in preference:
      +71.3 +/- 30.0 s/10 min, p < 0.05), but not for 0, 1, or 2 g/kg. By contrast,
      ORCHX males did not demonstrate conditioned preference for 3 g/kg EtOH (+16.0 +/-
      24.3 s/10 min, p > 0.05). In separate groups of mice, stimulus males (IS+)
      received EtOH during pairing to determine whether test mice prefer another
      intoxicated mouse. Both ORCHX+T and ORCHX test mice showed an increase in
      preference score for the IS+ mouse (ORCHX+T: +68.1 +/- 24.0 seconds; ORCHX: +58.9
      +/- 19.6 seconds, p < 0.05). CONCLUSIONS: These data demonstrate that EtOH
      promotes social preference in male mice, as it does in females. Testosterone
      enhances this effect.

PMID- 24460903
TI  - Comment on: long-term outcome of biopsy-proven lupus nephritis in Iran.

PMID- 24460902
TI  - Targeted gene mutation of E2F1 evokes age-dependent synaptic disruption and
      behavioral deficits.
AB  - Aberrant expression and activation of the cell cycle protein E2F1 in neurons has
      been implicated in many neurodegenerative diseases. As a transcription factor
      regulating G1 to S phase progression in proliferative cells, E2F1 is often up
      regulated and activated in models of neuronal death. However, despite its well
      studied functions in neuronal death, little is known regarding the role of E2F1
      in the mature brain. In this study, we used a combined approach to study the
      effect of E2F1 gene disruption on mouse behavior and brain biochemistry. We
      identified significant age-dependent olfactory and memory-related deficits in
      E2f1 mutant mice. In addition, we found that E2F1 exhibits punctated staining and
      localizes closely to the synapse. Furthermore, we found a mirroring age-dependent
      loss of post-synaptic protein-95 in the hippocampus and olfactory bulb as well as
      a global loss of several other synaptic proteins. Coincidently, E2F1 expression
      is significantly elevated at the ages, in which behavioral and synaptic
      perturbations were observed. Finally, we show that deficits in adult neurogenesis
      persist late in aged E2f1 mutant mice which may partially contribute to the
      behavior phenotypes. Taken together, our data suggest that the disruption of E2F1
      function leads to specific age-dependent behavioral deficits and synaptic
      perturbations. E2F1 is a transcription factor regulating cell cycle progression
      and apoptosis. Although E2F1 dysregulation under toxic conditions can lead to
      neuronal death, little is known about its physiologic activity in the healthy
      brain. Here, we report significant age-dependent olfactory and memory deficits in
      mice with dysfunctional E2F1. Coincident with these behavioral changes, we also
      found age-matched synaptic disruption and persisting reduction in adult
      neurogenesis. Our study demonstrates that E2F1 contributes to physiologic brain
      structure and function. 

PMID- 24460904
TI  - A pairwise relatedness estimator for polyploids.
AB  - Studies in genetics and ecology often require estimates of relatedness
      coefficients based on genetic marker data. Many diploid estimators have been
      developed using either method-of-moments or maximum-likelihood estimates.
      However, there are no relatedness estimators for polyploids. The development of a
      moment estimator for polyploids with polysomic inheritance, which simultaneously
      incorporates the two-gene relatedness coefficient and various 'higher-order'
      coefficients, is described here. The performance of the estimator is compared to
      other estimators under a variety of conditions. When using a small number of
      loci, the estimator is biased because of an increase in ill-conditioned matrices.
      However, the estimator becomes asymptotically unbiased with large numbers of
      loci. The ambiguity of polyploid heterozygotes (when balanced heterozygotes
      cannot be distinguished from unbalanced heterozygotes) is also considered; as
      with low numbers of loci, genotype ambiguity leads to bias. A software,
      PolyRelatedness, implementing this method and supporting a maximum ploidy of 8 is
      provided. 

PMID- 24460898
TI  - Genome sequencing and analysis of the paclitaxel-producing endophytic fungus
      Penicillium aurantiogriseum NRRL 62431.
AB  - BACKGROUND: Paclitaxel (TaxolTM) is an important anticancer drug with a unique
      mode of action. The biosynthesis of paclitaxel had been considered restricted to
      the Taxus species until it was discovered in Taxomyces andreanae, an endophytic
      fungus of T. brevifolia. Subsequently, paclitaxel was found in hazel (Corylus
      avellana L.) and in several other endophytic fungi. The distribution of
      paclitaxel in plants and endophytic fungi and the reported sequence homology of
      key genes in paclitaxel biosynthesis between plant and fungi species raises the
      question about whether the origin of this pathway in these two physically
      associated groups could have been facilitated by horizontal gene transfer.
      RESULTS: The ability of the endophytic fungus of hazel Penicillium
      aurantiogriseum NRRL 62431 to independently synthesize paclitaxel was established
      by liquid chromatography-mass spectrometry and proton nuclear magnetic resonance.
      The genome of Penicillium aurantiogriseum NRRL 62431 was sequenced and gene
      candidates that may be involved in paclitaxel biosynthesis were identified by
      comparison with the 13 known paclitaxel biosynthetic genes in Taxus. We found
      that paclitaxel biosynthetic gene candidates in P. aurantiogriseum NRRL 62431
      have evolved independently and that horizontal gene transfer between this
      endophytic fungus and its plant host is unlikely. CONCLUSIONS: Our findings shed
      new light on how paclitaxel-producing endophytic fungi synthesize paclitaxel, and
      will facilitate metabolic engineering for the industrial production of paclitaxel
      from fungi.

PMID- 24460905
TI  - Evaluation of support group interventions for children in troubled families:
      study protocol for a quasi-experimental control group study.
AB  - BACKGROUND: Support groups for children in troubled families are available in a
      majority of Swedish municipalities. They are used as a preventive effort for
      children in families with different parental problems such as addiction to
      alcohol/other drugs, mental illness, domestic violence, divorce situations, or
      even imprisonment. Children from families with these problems are a well-known at
      risk group for various mental health and social problems. Support groups aim at
      strengthening children's coping behaviour, to improve their mental health and to
      prevent a negative psycho-social development. To date, evaluations using a
      control-group study design are scarce. The aim of the current study is to
      evaluate the effects of support groups. This paper describes the design of an
      effectiveness study, initially intended as a randomized controlled trial, but
      instead is pursued as a quasi-experimental study using a non-randomized control
      group. METHODS/DESIGN: The aim is to include 116 children, aged 7-13 years and
      one parent/another closely related adult, in the study. Participants are
      recruited via existing support groups in the Stockholm county district and are
      allocated either into an intervention group or a waiting list control group,
      representing care as usual. The assessment consists of questionnaires that are to
      be filled in at baseline and at four months following the baseline. Additionally,
      the intervention group completes a 12-month follow-up. The outcomes include the
      Strength and Difficulties Questionnaire (SDQ S11-16), the Kids Coping Scale, the
      "Ladder of life" which measures overall life satisfaction, and "Jag tycker jag
      ar" (I think I am) which measures self-perception and self-esteem. The parents
      complete the SDQ P4-16 (parent-report version) and the Swedish scale
      "Familjeklimat" (Family Climate), which measures the emotional climate in the
      family. DISCUSSION: There is a need for evaluating the effects of support groups
      targeted to children from troubled families. This quasi-experimental study
      therefore makes an important contribution to this novel field of research. In the
      article various problems related to pursuing a study with children at risk are
      discussed. TRIAL REGISTRATION: ISRCTN52310507.

PMID- 24460907
TI  - Effect of T-DNA insertions on mRNA transcript copy numbers upstream and
      downstream of the insertion site in Arabidopsis thaliana explored by surface
      enhanced Raman spectroscopy.
AB  - We report the effect of a T-DNA insertion on the expression level of mRNA
      transcripts of the TWISTED DWARF 1 (TWD1) gene upstream and downstream of the T
      DNA insertion site in Arabidopsis. A novel approach based on surface-enhanced
      Raman spectroscopy (SERS) was developed to detect and quantify the effect of a T
      DNA insertion on mRNA transcript accumulation at 5'- and 3'-ends of the TWD1
      gene. A T-DNA insertion mutant in the TWD1 gene (twd1-2) was chosen to test the
      sensitivity and the feasibility of the approach. The null mutant of the FK506
      like immunophilin protein TWD1 in Arabidopsis shows severe dwarfism and strong
      disoriented growth of plant organs. A spontaneous arising suppressor allele of
      twd1-2 called twd-sup displayed an intermediate phenotype between wild type and
      the knockout phenotype of twd1-2. Both twd1 mutant alleles have identical DNA
      sequences at the TWD1 locus including the T-DNA insertion in the fourth intron of
      the TWD1 gene but they show clear variability in the mutant phenotype. We present
      here the development and application of SERS-based mRNA detection and
      quantification using the expression of the TWD1 gene in wild type and both mutant
      alleles. The hallmarks of our SERS approach are a robust and fast assay to detect
      up to 0.10 fm of target molecules including the ability to omit in vitro
      transcription and amplification steps after RNA isolation. Instead we perform
      direct quantification of RNA molecules. This enables us to detect and quantify
      rare RNA molecules at high levels of precision and sensitivity.

PMID- 24460906
TI  - Safewards: the empirical basis of the model and a critical appraisal.
AB  - ACCESSIBLE SUMMARY: In the previous paper we described a model explaining
      differences in rates of conflict and containment between wards, grouping causal
      factors into six domains: the staff team, the physical environment, outside
      hospital, the patient community, patient characteristics and the regulatory
      framework. This paper reviews and evaluates the evidence for the model from
      previously published research. The model is supported, but the evidence is not
      very strong. More research using more rigorous methods is required in order to
      confirm or improve this model. ABSTRACT: In a previous paper, we described a
      proposed model explaining differences in rates of conflict (aggression,
      absconding, self-harm, etc.) and containment (seclusion, special observation,
      manual restraint, etc.). The Safewards Model identified six originating domains
      as sources of conflict and containment: the patient community, patient
      characteristics, the regulatory framework, the staff team, the physical
      environment, and outside hospital. In this paper, we assemble the evidence
      underpinning the inclusion of these six domains, drawing upon a wide ranging
      review of the literature across all conflict and containment items; our own
      programme of research; and reasoned thinking. There is good evidence that the six
      domains are important in conflict and containment generation. Specific claims
      about single items within those domains are more difficult to support with
      convincing evidence, although the weight of evidence does vary between items and
      between different types of conflict behaviour or containment method. The
      Safewards Model is supported by the evidence, but that evidence is not
      particularly strong. There is a dearth of rigorous outcome studies and trials in
      this area, and an excess of descriptive studies. The model allows the generation
      of a number of different interventions in order to reduce rates of conflict and
      containment, and properly conducted trials are now needed to test its validity.

PMID- 24460908
TI  - PRC1 components exhibit different binding kinetics in Polycomb bodies.
AB  - BACKGROUND INFORMATION: Polycomb group (PcG) proteins keep the memory of cell
      identity by maintaining the repression of numerous target genes. They accumulate
      into nuclear foci called Polycomb bodies, which function in Drosophila cells as
      silencing compartments where PcG target genes convene. PcG proteins also exert
      their activities elsewhere in the nucleoplasm. In mammalian cells, the dynamic
      organisation and function of Polycomb bodies remain to be determined. RESULTS:
      Fluorescently tagged PcG proteins CBXs and their partners BMI1 and RING1 form
      foci of different sizes and intensities in human U2OS cells. Fluorescence
      recovery after photobleaching (FRAP) analysis reveals that PcG dynamics outside
      foci is governed by diffusion as complexes and transient binding. In sharp
      contrast, recovery curves inside foci are substantially slower and exhibit large
      variability. The slow binding component amplitudes correlate with the intensities
      and sizes of these foci, suggesting that foci contained varying numbers of
      binding sites. CBX4-green fluorescent protein (GFP) foci were more stable than
      CBX8-GFP foci; yet the presence of CBX4 or CBX8-GFP in the same focus had a minor
      impact on BMI1 and RING1 recovery kinetics. CONCLUSION: We propose that FRAP
      recovery curves provide information about PcG binding to their target genes
      outside foci and about PcG spreading onto chromatin inside foci.

PMID- 24460909
TI  - Deregulation of the phosphatase, PP2A is a common event in breast cancer,
      predicting sensitivity to FTY720.
AB  - BACKGROUND: The most commonly used biomarkers to predict the response of breast
      cancer patients to therapy are the oestrogen receptor (ER), progesterone receptor
      (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for
      these biomarkers are eligible for specific therapies such as endocrine treatment
      in the event of ER and PgR positivity, and the monoclonal antibody, trastuzumab,
      in the case of HER2-positive patients. Patients who are negative for these three
      biomarkers, the so-called triple negatives, however, derive little benefit from
      such therapies and are associated with a worse prognosis. Deregulation of the
      protein serine/threonine phosphatase type 2A (PP2A) and its regulatory subunits
      is a common event in breast cancer, providing a possible target for therapy.
      METHODS: The data portal, cBioPortal for Cancer Genomics was used to investigate
      the incidence of conditions that are associated with low phosphatase activity.
      Four (4) adherent human breast cancer cell lines, MDA-MB-468, MDA-MB-436, Hs578T
      and BT-20 were cultured to assess their viability when exposed to various dosages
      of rapamycin or FTY720. In addition, RNA was extracted and cDNA was synthesised
      to amplify the coding sequence of PPP2CA. Amplification was followed by high
      resolution melting to identify variations. RESULTS AND CONCLUSION: The sequence
      of PPP2CA was found to be conserved across a diverse panel of solid tumour and
      haematological cell lines, suggesting that low expression of PPP2CA and
      differential binding of inhibitory PPP2CA regulators are the main mechanisms of
      PP2A deregulation. Interestingly, the cBioPortal for Cancer Genomics shows that
      PP2A is deregulated in 59.6% of basal breast tumours. Viability assays performed
      to determine the sensitivity of a panel of breast cancer cell lines to FTY720, a
      PP2A activator, indicated that cell lines associated with ER loss are sensitive
      to lower doses of FTY720. The subset of patients with suppressed PP2A activity is
      potentially eligible for treatment using therapies which target the PI3K/AKT/mTOR
      pathway, such as phosphatase activators.

PMID- 24460910
TI  - Hexavalent vaccines for immunization in paediatric age.
AB  - Despite the potential for protection against a broad spectrum of pathogens, the
      availability of an increased number of effective vaccines could lead to a
      significant reduction in vaccination coverage as the result of issues with
      implementation of new vaccines within existing protocols. To overcome these
      problems, the development of combined vaccines has been promoted. The use of
      combined vaccines offers a number of potential benefits, including a reduction in
      the number of patient visits, reduced complications associated with multiple
      intramuscular injections, decreased costs of stocking and administering separate
      vaccines, and a lowering of the risk of delayed or missed vaccinations. The
      hexavalent vaccine includes antigens against diphtheria, tetanus, acellular
      pertussis (DTaP), hepatitis B (HBsAg), poliomyelitis (P1, P2, P3) and Haemophilus
      influenzae type B (Hib) infections. The primary goal of this review is to discuss
      the immunogenicity, efficacy, safety and tolerability of several hexavalent
      preparations that are either commercially available or still under development. 

PMID- 24460911
TI  - Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy
      horses and horses with recurrent airway obstruction (RAO).
AB  - BACKGROUND: Dysregulation of apoptosis has been implicated in a range of diseases
      including tumors, neurodegenerative and autoimmune diseases, as well as allergic
      asthma and chronic obstructive pulmonary disease (COPD) in humans. Although it
      has a different pathophysiology, delayed apoptosis of various inflammatory cells
      may play a pivotal role in the development of recurrent airway obstruction (RAO)
      in horses. Reduction of inflammatory cell apoptosis or a dysregulation of this
      process could lead to chronic inflammation and tissue injury. Therefore, the aim
      of this study was to investigate the rate of apoptosis and necrosis of
      neutrophils and macrophages in bronchoalveolar lavage fluid obtained from seven
      horses suffering from RAO (study group) and seven control horses. RESULTS: We
      demonstrated that neutrophil/macrophage apoptosis is altered in RAO-affected
      horses compared with the control group in the BAL fluid. We found a significant
      difference between the median percentage of early and late apoptosis of
      neutrophils between the study and control group of horses. Moreover, we found a
      positive correlation between the rate of apoptosis and the median percentage of
      macrophages in RAO-affected horses. CONCLUSION: The findings suggest that
      apoptosis dysregulation may play a significant role in the pathogenesis of RAO.
      However, further studies are needed to clarify the role of altered apoptosis in
      the course of equine recurrent airway obstruction.

PMID- 24460913
TI  - Management of cochlear implant device extrusion: case series and literature
      review.
AB  - INTRODUCTION AND AIMS: Cochlear implants have enabled an improved quality of life
      for many patients with deafness. Implant extrusion and skin flap necrosis are the
      most common complications associated with implant use. We report our management
      of patients presenting with complications as a result of cochlear implant
      insertion. The goal of surgery was to achieve a stable, healed wound for use as a
      cochlear device implantation site. METHODS AND RESULTS: We describe a series of
      patients presenting with skin flap necrosis and/or extrusion of their cochlear
      implant. The reconstructive options employed are discussed. CONCLUSION: Surgeons
      should be aware of the reconstructive options available in such circumstances,
      and should choose appropriate management depending on the clinical situation, in
      order to optimise the functional result for the patient.

PMID- 24460914
TI  - Limited ectrodactyly, ectodermal dysplasia and cleft lip-palate syndrome with a
      p63 mutation, associated with linear and whorled naevoid hypermelanosis.

PMID- 24460915
TI  - Bacterial taxa-area and distance-decay relationships in marine environments.
AB  - The taxa-area relationship (TAR) and the distance-decay relationship (DDR) both
      describe spatial turnover of taxa and are central patterns of biodiversity. Here,
      we compared TAR and DDR of bacterial communities across different marine realms
      and ecosystems at the global scale. To obtain reliable global estimates for both
      relationships, we quantified the poorly assessed effects of sequencing depth,
      rare taxa removal and number of sampling sites. Slope coefficients of bacterial
      TARs were within the range of those of plants and animals, whereas slope
      coefficients of bacterial DDR were much lower. Slope coefficients were mostly
      affected by removing rare taxa and by the number of sampling sites considered in
      the calculations. TAR and DDR slope coefficients were overestimated at sequencing
      depth <4000 sequences per sample. Noticeably, bacterial TAR and DDR patterns did
      not correlate with each other both within and across ecosystem types, suggesting
      that (i) TAR cannot be directly derived from DDR and (ii) TAR and DDR may be
      influenced by different ecological factors. Nevertheless, we found marine
      bacterial TAR and DDR to be steeper in ecosystems associated with high
      environmental heterogeneity or spatial isolation, namely marine sediments and
      coastal environments compared with pelagic ecosystems. Hence, our study provides
      information on macroecological patterns of marine bacteria, as well as
      methodological and conceptual insights, at a time when biodiversity surveys
      increasingly make use of high-throughput sequencing technologies. 

PMID- 24460916
TI  - Beyond enhanced recovery?

PMID- 24460918
TI  - Better care for complex, challenging clients: Hawaii's training program to
      improve residential long-term care.
AB  - The Kupuna Adult Care Home Project is an innovative training program designed to
      improve the skills of care home and adult foster home operators in Hawaii.
      Clients in residential settings are increasingly likely to have complex problems.
      The project developed nine modules on topics such as dementia care, diabetes, and
      fall prevention based on stakeholder input and a national scan of best practices.
      A total of 787 persons were trained. An evaluation indicated that training
      significantly improved knowledge and that trainees were highly satisfied with the
      training. A secondary State of the Industry survey indicated that many care home
      and adult foster home caregivers are aging themselves and their children may not
      take over the family business. By combining practical knowledge and active
      learning strategies to work through real-life scenarios, the Kupuna Adult Care
      Home project is a promising training model. 

PMID- 24460920
TI  - Field study site selection, species abundance and monthly distribution of
      anopheline mosquitoes in the northern Kruger National Park, South Africa.
AB  - BACKGROUND: Knowledge of the ecology and behaviour of a target species is a
      prerequisite for the successful development of any vector control strategy.
      Before the implementation of any strategy it is essential to have comprehensive
      information on the bionomics of species in the targeted area. The aims of this
      study were to conduct regular entomological surveillance and to determine the
      relative abundance of anopheline species in the northern Kruger National Park. In
      addition to this, the impact of weather conditions on an Anopheles arabiensis
      population were evaluated and a range of mosquito collection methods were
      assessed. METHODS: A survey of Anopheles species was made between July 2010 and
      December 2012. Mosquitoes were collected from five sites in the northern Kruger
      National Park, using carbon dioxide-baited traps, human landing and larval
      collections. Specimens were identified morphologically and polymerase chain
      reaction assays were subsequently used where appropriate. RESULTS: A total of
      3,311 specimens belonging to nine different taxa was collected. Species collected
      were: Anopheles arabiensis (n = 1,352), Anopheles quadriannulatus (n = 870),
      Anopheles coustani (n = 395), Anopheles merus (n = 349), Anopheles pretoriensis
      (n = 35), Anopheles maculipalpis (n = 28), Anopheles rivulorum (n = 19),
      Anopheles squamosus (n = 3) and Anopheles rufipes (n = 2). Members of the
      Anopheles gambiae species complex were the most abundant and widely distributed,
      occurring across all collection sites. The highest number of mosquitoes was
      collected using CO2 baited net traps (58.2%) followed by human landing catches
      (24.8%). Larval collections (17%) provided an additional method to increase
      sample size. Mosquito sampling productivity was influenced by prevailing weather
      conditions and overall population densities fluctuated with seasons. CONCLUSION:
      Several anopheline species occur in the northern Kruger National Park and their
      densities fluctuate between seasons. Species abundance and relative proportions
      within the An. gambiae complex varied between collection methods. There is a
      perennial presence of an isolated population of An. arabiensis at the
      Malahlapanga site which declined in density during the dry winter months, making
      this site suitable for a small pilot study site for Sterile Insect Technique as a
      malaria vector control strategy.

PMID- 24460921
TI  - The acquisition of SV order in unaccusatives: manipulating the definiteness of
      the NP argument.
AB  - In two sentence repetition experiments, we investigated whether four- and five
      year-olds master distinct representations for intransitive verb classes by
      testing two syntactic analyses of unaccusatives (Burzio, 1986; Belletti, 1988).
      Under the assumption that, with unaccusatives, the partitive case of the
      postverbal argument is realized only on indefinites (Belletti, 1988), we tested
      whether children used indefiniteness as a feature to assign the partitive case to
      the verb's argument. In the sentences, we manipulated whether the subject
      preceded or followed the (unaccusative or unergative) verb and whether the
      subject was expressed by means of a definite or indefinite NP. With
      unaccusatives, children tended to place the subject in the postverbal position
      when the subject NP was indefinite, whereas, when the sentence presented a
      definite postverbal subject, children preferred to place the definite subject in
      the preverbal position. Definiteness exerted an effect only with unaccusatives,
      suggesting that children treated unergatives and unaccusatives differently.

PMID- 24460919
TI  - Altered cerebellum development and dopamine distribution in a rat genetic model
      with congenital hypothyroidism.
AB  - Thyroid hormones play crucial roles in the development and functional maintenance
      of the central nervous system. Despite extensive studies of the neural function
      of thyroid hormones, little is known about the effects of hypothyroidism on
      behavioural traits and the mechanisms underlying such effects. In the present
      study, we report an investigation of congenitally hypothyroid mutant rdw rats,
      revealing a novel function of thyroid hormones in the central nervous system. The
      rdw rats were subjected to behavioural analyses such as the rotarod test, open
      field test and circadian activity measurement. To determine the cause of
      behavioural disorders, cerebellar morphogenesis was examined by
      immunohistochemical analysis, and the axonal transport of dopamine in the
      nigrostriatal pathway was analysed by high-performance liquid chromatography and
      western blotting. The effects of thyroxine administration to the rdw rats were
      examined by behavioural analysis. The rdw rats showed severe impairment of motor
      coordination and balance. This could be explained by the fact that the rats
      showed severe retardation of cerebellar morphogenesis, which correlates with the
      small somata and poor dendritic arborisation of Purkinje cells and retarded
      migration of granule cells particularly during the first two postnatal weeks.
      Moreover, the rdw rats showed hypoactivity, characterised by decreased circadian
      locomotor activity. After weaning, thyroxine administration improved the dwarfism
      in rdw rats but had no effect on cerebellar function. In addition, the rdw rats
      showed anxiety and depression intrinsically to novel surroundings. Interestingly,
      the rdw rats showed high levels of dopamine in the substantia nigra and low
      levels in the striatum, an important centre for the coordination of behaviour.
      Furthermore, low levels of tubulin in the striatum were detected, indicating the
      aberrant axonal transport of dopamine in the nigrostriatal pathway as a result of
      the reduced delivery of microtubules. These findings indicate an important
      function of thyroid hormones in cerebellar formation and in the regulation of
      axonal transport of dopamine. Moreover, rdw rats will be useful for studies of
      brain function and behavioural disorders in congenital hypothyroidism. 

PMID- 24460922
TI  - Effects of alfalfa meal on the intestinal microbial diversity and immunity of
      growing ducks.
AB  - This study was conducted to investigate the effects of alfalfa meal diets on the
      intestinal microbial diversity and immunity of growing egg-type ducks. A total of
      128 healthy 7-week-old female egg-type Shaoxing ducks were selected and randomly
      assigned into four dietary treatments: 0%, 3%, 6% and 9% alfalfa meal for 8
      weeks. Each treatment consisted of four replicates of eight ducks each.
      Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) was
      used to characterize the microbiota. The results showed that the DGGE
      fingerprints of the V6-V8 fragments of the 16S rRNA from the caeca and faeces of
      ducks fed 3%, 6% and 9% alfalfa meal had significantly higher microbiota species
      richness than those fed 0% alfalfa meal (p < 0.05). The Shannon-Weiner index of
      the microbiota from the caeca and faeces of ducks fed 3%, 6% and 9% alfalfa meal
      was significantly higher than those fed 0% alfalfa meal (p < 0.05). Molecular
      analysis of the caecal and faecal DNA extracts showed that the alfalfa meal diet
      promotes the intestinal microbial diversity, as indicated by their higher species
      richness and Shannon-Weiner index. However, the groups did not significantly
      differ in terms of average daily gain, feed intake and gain-to-feed ratio (p >
      0.05), and the 3-9% alfalfa meal did not affect the growth performance of the
      growing egg-type ducks. The proliferation of T and B lymphocytes was
      significantly greater (p < 0.05) in the groups supplemented with 3%, 6% and 9% of
      alfalfa meal than the unsupplemented control group, and alfalfa meal promoted the
      lymphocytes proliferation of the growing egg-type ducks. Dietary alfalfa meal
      supplementation increases intestinal microbial community diversity and improves
      of the immune response growing egg-type ducks.

PMID- 24460924
TI  - Serum miR-206 and other muscle-specific microRNAs as non-invasive biomarkers for
      Duchenne muscular dystrophy.
AB  - Creatine kinase has been utilized as a diagnostic marker for Duchenne muscular
      dystrophy (DMD), but it correlates less well with the DMD pathological
      progression. In this study, we hypothesized that muscle-specific microRNAs (miR
      1, -133, and -206) in serum may be useful for monitoring the DMD pathological
      progression, and explored the possibility of these miRNAs as potential non
      invasive biomarkers for the disease. By using real-time quantitative reverse
      transcription-polymerase chain reaction in a randomized and controlled trial, we
      detected that miR-1, -133, and -206 were significantly over-expressed in the
      serum of 39 children with DMD (up to 3.20 +/- 1.20, 2(-DeltaDeltaCt) ): almost 2-
      to 4-fold enriched in comparison to samples from the healthy controls (less than
      1.15 +/- 0.34, 2(-DeltaDeltaCt) ). To determine whether these miRNAs were related
      to the clinical features of children with DMD, we analyzed the associations
      compared to creatine kinase. There were very good inverse correlations between
      the levels of these miRNAs, especially miR-206, and functional performances: high
      levels corresponded to low muscle strength, muscle function, and quality of life.
      Moreover, by receiver operating characteristic curves analyses, we revealed that
      these miRNAs, especially miR-206, were able to discriminate DMD from controls.
      Thus, miR-206 and other muscle-specific miRNAs in serum are useful for monitoring
      the DMD pathological progression, and hence as potential non-invasive biomarkers
      for the disease. There has been a long-standing need for reliable, non-invasive
      biomarkers for Duchenne muscular dystrophy (DMD). We found that the levels of
      muscle-specific microRNAs, especially miR-206, in the serum of DMD were 2- to 4
      fold higher than in the controls. High levels corresponded to low muscle
      strength, muscle function, and quality of life (QoL). These miRNAs were able to
      discriminate DMD from controls by receiver operating characteristic (ROC) curves
      analyses. Thus, miR-206 and other muscle-specific miRNAs are useful as non
      invasive biomarkers for DMD.

PMID- 24460923
TI  - Mitrecin A, an endolysin-like bacteriolytic enzyme from a newly isolated soil
      streptomycete.
AB  - An open reading frame with homology to known endolysin genes was identified in
      the genome of Streptomyces sp. strain 212, which is a newly isolated soil
      bacterium. The heterologously expressed gene product of this endolysin-like gene,
      called Mitrecin A, demonstrated bacteriolytic activity against several Gram
      negative bacteria. The genome of the bacterial strain was sequenced to draft
      quality using pyrosequencing followed by genome assembly and gene annotation.
      Within the sequence, a chromosomally located endolysin-like open reading frame
      was predicted. The gene product, designated Mitrecin A, was heterologously
      expressed and isolated from contaminating proteins as a fusion protein to a 6
      histidine tag. Mitrecin A consists of 127 amino acids arranged in modular domains
      of activity. It has an estimated molecular weight of 14.3 kDa and retains
      sequence homology to the M15C peptidase subfamily of zinc
      metallocarboxypeptidases. The heat-labile purified recombinant protein has an
      overall positive charge, has optimal catalytic activities at 26 degrees C in
      solution of pH 9 with 1% saline and has bacteriolytic activity against Gram
      negative bacteria of the medically important genera Aeromonas, Escherichia,
      Salmonella, Shigella, Vibrio and Yersinia. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The gene of a new protein antimicrobial, Mitrecin A, was discovered in the genome
      of a soil bacterium. The purified recombinant enzyme, resulting from heterologous
      over expression of the gene, was found to be tolerant of increased pH conditions
      and to have bacteriolytic activity against Gram-negative bacteria of the
      medically important genera Aeromonas, Escherichia, Salmonella, Shigella, Vibrio
      and Yersinia. Characterization of enzymes such as Mitrecin A from previously
      uncharacterized bacteria provides potential options for new biocontrol agents in
      medically and economically important applications like therapeutics,
      disinfectants, food preservatives, agricultural livestock antimicrobials, and
      inhibitors of biofilm production.

PMID- 24460925
TI  - The association between C-reactive protein and delirium in 710 acute elderly
      hospital admissions.
AB  - BACKGROUND: Delirium is a common neuropsychiatric syndrome associated with poor
      outcomes. Evidence supports a neuroinflammatory etiology, but the role of the
      inflammatory marker C-reactive protein (C-RP) remains unclear. We investigated
      the relationship between C-RP and delirium and its severity as well as
      interaction with medical diagnosis. METHODS: From an existing database (710
      patients over 70 years old admitted to a Medical Acute Admissions Unit) we
      analyzed data which included C-RP levels, delirium (using the Confusion
      Assessment Method), and other clinical and demographic factors. Primary diagnoses
      were grouped (cardiovascular, musculoskeletal, infection, metabolic, and other).
      RESULTS: There was a strong association between elevated C-RP and delirium (t =
      5.09; p < 0.001), independent of other potential risk factors for delirium (odds
      ratio (OR) = 1.32 (95% CI: 1.10-1.58) p = 0.003). There was no significant
      association between C-RP and delirium severity, and between C-RP and delirium in
      the populations with cardiovascular disease, infection upon admission, or from
      the metabolic group despite an OR of 2.24 (95% CI: 0.92-5.45). There was an
      association in the musculoskeletal group (OR 2.19 (95% CI: 1.19-4.02)).
      CONCLUSIONS: There is an association between elevated C-RP and delirium. This is
      strongest in patients admitted with musculoskeletal disease but not in others,
      implying that C-RP is involved in the genesis of delirium in musculoskeletal
      disease, but that other factors or processes may be more important in those with
      cardiovascular disease or infection.

PMID- 24460926
TI  - Involvement of plant endogenous ABA in Bacillus megaterium PGPR activity in
      tomato plants.
AB  - BACKGROUND: Plant growth-promoting rhizobacteria (PGPR) are naturally occurring
      soil bacteria which benefit plants by improving plant productivity and immunity.
      The mechanisms involved in these processes include the regulation of plant
      hormone levels such as ethylene and abscisic acid (ABA). The aim of the present
      study was to determine whether the activity of Bacillus megaterium PGPR is
      affected by the endogenous ABA content of the host plant. The ABA-deficient
      tomato mutants flacca and sitiens and their near-isogenic wild-type parental
      lines were used. Growth, stomatal conductance, shoot hormone concentration,
      competition assay for colonization of tomato root tips, and root expression of
      plant genes expected to be modulated by ABA and PGPR were examined. RESULTS:
      Contrary to the wild-type plants in which PGPR stimulated growth rates, PGPR
      caused growth inhibition in ABA-deficient mutant plants. PGPR also triggered an
      over accumulation of ethylene in ABA-deficient plants which correlated with a
      higher expression of the pathogenesis-related gene Sl-PR1b. CONCLUSIONS: Positive
      correlation between over-accumulation of ethylene and a higher expression of Sl
      PR1b in ABA-deficient mutant plants could indicate that maintenance of normal
      plant endogenous ABA content may be essential for the growth promoting action of
      B. megaterium by keeping low levels of ethylene production.

PMID- 24460927
TI  - How necessary is the unconscious as a predictive, explanatory, or prescriptive
      construct?
AB  - We elucidate the epistemological futility of using concepts such as unconscious
      thinking in research. Focusing on Newell & Shanks' (N&S's) use of the lens model
      as a framework, we clarify issues with regard to unconscious-thought theory (UTT)
      and self-insight studies. We examine these key points: Brunswikian psychology is
      absent in UTT; research on self-insight did not emerge to explore the
      unconscious; the accuracy of judgments does not necessitate the unconscious; and
      the prescriptive claim of UTT is unfounded. 

PMID- 24460928
TI  - GS-9219/VDC-1101--a prodrug of the acyclic nucleotide PMEG has antitumor activity
      in spontaneous canine multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is an important human and canine cancer for
      which novel therapies remain necessary. VDC-1101 (formerly GS-9219), a novel
      double prodrug of the anti-proliferative nucleotide analog 9-(2
      phosphonylmethoxyethyl) guanine (PMEG), possesses potent cytotoxic activity in
      vitro in human lymphoblasts and leukemia cell lines and in vivo in spontaneous
      canine lymphoma. Given the similarity in lineage between lymphoma and MM, we
      hypothesized that VDC-1101 would be active against MM. RESULTS: We evaluated the
      in vitro antiproliferative effects of VDC-1101 against 3 human MM cell lines, and
      we performed a phase-II clinical trial in 14 dogs with spontaneous MM. Each dog
      was treated with a maximum of 6 doses of VDC-1101 monotherapy over 10-15 weeks.
      Dose-dependent antiproliferative activity was observed in all evaluated cell
      lines. Major antitumor responses (reduction of serum paraprotein and resolution
      of hypercalcemia, peripheral cytopenias and bone marrow plasmacytosis) were
      observed in 9 of 11 evaluable dogs for a median of 172 days, including a durable
      stringent complete response (>1047 days) in a dog with melphalan-refractory
      disease. 2 dogs were euthanized due to presumed pulmonary fibrosis; there were no
      other dose-limiting toxicities encountered. CONCLUSIONS: In conclusion, VDC-1101
      has significant anti-tumor activity at well-tolerated doses in spontaneous canine
      MM.

PMID- 24460930
TI  - Voxel-wise quantification of myocardial blood flow with cardiovascular magnetic
      resonance: effect of variations in methodology and validation with positron
      emission tomography.
AB  - BACKGROUND: Quantitative assessment of myocardial blood flow (MBF) from
      cardiovascular magnetic resonance (CMR) perfusion images appears to offer
      advantages over qualitative assessment. Currently however, clinical translation
      is lacking, at least in part due to considerable disparity in quantification
      methodology. The aim of this study was to evaluate the effect of common
      methodological differences in CMR voxel-wise measurement of MBF, using position
      emission tomography (PET) as external validation. METHODS: Eighteen subjects,
      including 9 with significant coronary artery disease (CAD) and 9 healthy
      volunteers prospectively underwent perfusion CMR. Comparison was made between MBF
      quantified using: 1. Calculated contrast agent concentration curves (to correct
      for signal saturation) versus raw signal intensity curves; 2. Mid-ventricular
      versus basal-ventricular short-axis arterial input function (AIF) extraction; 3.
      Three different deconvolution approaches; Fermi function parameterization,
      truncated singular value decomposition (TSVD) and first-order Tikhonov
      regularization with b-splines. CAD patients also prospectively underwent rubidium
      82 PET (median interval 7 days). RESULTS: MBF was significantly higher when
      calculated using signal intensity compared to contrast agent concentration
      curves, and when the AIF was extracted from mid- compared to basal-ventricular
      images. MBF did not differ significantly between Fermi and Tikhonov, or between
      Fermi and TVSD deconvolution methods although there was a small difference
      between TSVD and Tikhonov (0.06 mL/min/g). Agreement between all deconvolution
      methods was high. MBF derived using each CMR deconvolution method showed a
      significant linear relationship (p<0.001) with PET-derived MBF however each
      method underestimated MBF compared to PET (by 0.19 to 0.35 mL/min/g).
      CONCLUSIONS: Variations in more complex methodological factors such as
      deconvolution method have no greater effect on estimated MBF than simple factors
      such as AIF location and observer variability. Standardization of the
      quantification process will aid comparison between studies and may help CMR MBF
      quantification enter clinical use.

PMID- 24460931
TI  - Molecular Characterization of Foot-and-Mouth Disease Viruses Collected in
      Tanzania Between 1967 and 2009.
AB  - This paper describes the molecular characterization of foot-and-mouth disease
      viruses (FMDV) recovered from outbreaks in Tanzania that occurred between 1967
      and 2009. A total of 44 FMDV isolates, containing representatives of serotypes O,
      A, SAT 1 and SAT 2 from 13 regions of Tanzania, were selected from the FAO World
      Reference Laboratory for FMD (WRLFMD) virus collection. VP1 nucleotide sequences
      were determined for RT-PCR amplicons, and phylogenetic reconstructions were
      determined by maximum likelihood and neighbour-joining methods. These analyses
      showed that Tanzanian type O viruses fell into the EAST AFRICA 2 (EA-2) topotype,
      type A viruses fell into the AFRICA topotype (genotype I), type SAT 1 viruses
      into topotype I and type SAT 2 viruses into topotype IV. Taken together, these
      findings reveal that serotypes O, A, SAT 1 and SAT 2 that caused FMD outbreaks in
      Tanzania were genetically related to lineages and topotypes occurring in the East
      African region. The close genetic relationship of viruses in Tanzania to those
      from other countries suggests that animal movements can contribute to virus
      dispersal in sub-Saharan Africa. This is the first molecular description of
      viruses circulating in Tanzania and highlights the need for further sampling of
      representative viruses from the region so as to elucidate the complex
      epidemiology of FMD in Tanzania and sub-Saharan Africa.

PMID- 24460929
TI  - Sequential adaptive introgression of the mitochondrial genome in Drosophila
      yakuba and Drosophila santomea.
AB  - Interspecific hybridization provides the unique opportunity for species to tap
      into genetic variation present in a closely related species and potentially take
      advantage of beneficial alleles. It has become increasingly clear that when
      hybridization occurs, mitochondrial DNA (mtDNA) often crosses species boundaries,
      raising the possibility that it could serve as a recurrent target of natural
      selection and source of species' adaptations. Here we report the sequences of 46
      complete mitochondrial genomes of Drosophila yakuba and Drosophila santomea, two
      sister species known to produce hybrids in nature (~3%). At least two independent
      events of mtDNA introgression are uncovered in this study, including an early
      invasion of the D. yakuba mitochondrial genome that fully replaced the D.
      santomea mtDNA native haplotypes and a more recent, ongoing event centred in the
      hybrid zone. Interestingly, this recent introgression event bears the signature
      of Darwinian natural selection, and the selective haplotype can be found at low
      frequency in Africa mainland populations of D. yakuba. We put forward the
      possibility that, because the effective population size of D. santomea is smaller
      than that of D. yakuba, the faster accumulation of mildly deleterious mutations
      associated with Muller's ratchet in the former species may have facilitated the
      replacement of the mutationally loaded mitochondrial genome of D. santomea by
      that of D. yakuba. 

PMID- 24460932
TI  - Contact endoscopy as a novel technique in the detection and diagnosis of oral
      cavity and oropharyngeal mucosal lesions in the head and neck.
AB  - OBJECTIVE: We aimed to investigate the diagnostic accuracy of contact endoscopy
      in evaluating oral and oropharyngeal mucosal lesions. METHODS: Between January
      2010 and December 2011, 34 patients with lesions of the oral and oropharyngeal
      mucosa were enrolled in the study. Comparison between initial contact endoscopy
      results and 'gold standard' tissue biopsy was undertaken. RESULTS: Nine patients
      had histologically confirmed squamous cell carcinoma, 2 had carcinoma in situ, 3
      had dysplastic lesions and 20 patients had various benign lesions. Contact
      endoscopy demonstrated sensitivity and specificity of 89 and 100 per cent
      respectively in the evaluation of malignant lesions. Benign lesions were
      correctly categorised in 50 per cent of cases (10/20). The video images from
      contact endoscopy could not be interpreted in six cases. CONCLUSIONS: Contact
      endoscopy demonstrates high sensitivity and specificity in the imaging of
      malignant lesions with reduced reliability in the evaluation of benign lesions.
      Significant shortcomings also exist in the design of current technology that we
      believe represent a significant barrier to the reliable collection of useful
      video data.

PMID- 24460933
TI  - Language evolution can be shaped by the structure of the world.
AB  - Human languages vary in many ways but also show striking cross-linguistic
      universals. Why do these universals exist? Recent theoretical results demonstrate
      that Bayesian learners transmitting language to each other through iterated
      learning will converge on a distribution of languages that depends only on their
      prior biases about language and the quantity of data transmitted at each point;
      the structure of the world being communicated about plays no role (Griffiths &
      Kalish, 2005, 2007). We revisit these findings and show that when certain
      assumptions about the relationship between language and the world are abandoned,
      learners will converge to languages that depend on the structure of the world as
      well as their prior biases. These theoretical results are supported with a series
      of experiments showing that when human learners acquire language through iterated
      learning, the ultimate structure of those languages is shaped by the structure of
      the meanings to be communicated.

PMID- 24460934
TI  - Metabolic states with maximal specific rate carry flux through an elementary flux
      mode.
AB  - Specific product formation rates and cellular growth rates are important
      maximization targets in biotechnology and microbial evolution. Maximization of a
      specific rate (i.e. a rate expressed per unit biomass amount) requires the
      expression of particular metabolic pathways at optimal enzyme concentrations. In
      contrast to the prediction of maximal product yields, any prediction of optimal
      specific rates at the genome scale is currently computationally intractable, even
      if the kinetic properties of all enzymes are available. In the present study, we
      characterize maximal-specific-rate states of metabolic networks of arbitrary size
      and complexity, including genome-scale kinetic models. We report that optimal
      states are elementary flux modes, which are minimal metabolic networks operating
      at a thermodynamically-feasible steady state with one independent flux.
      Remarkably, elementary flux modes rely only on reaction stoichiometry, yet they
      function as the optimal states of mathematical models incorporating enzyme
      kinetics. Our results pave the way for the optimization of genome-scale kinetic
      models because they offer huge simplifications to overcome the concomitant
      computational problems. 

PMID- 24460935
TI  - Intratumor heterogeneity: nature and biological significance.
AB  - Intratumor heterogeneity inherent in the majority of human cancers is a major
      obstacle for a highly efficient diagnosis and successful prognosis and treatment
      of these diseases. Being a result of clonal diversity within the same tumor,
      intratumor heterogeneity can be manifested in variability of genetic and
      epigenetic status, gene and protein expression, morphological structure, and
      other features of the tumor. It is most likely that the appearance of this
      diversity is a source for the adaptation of the tumor to changes in
      microenvironmental conditions and/or a tool for changing its malignant potential.
      In any case, both processes result in the appearance of cell clones with
      different undetermined sets of hallmarks. In this review, we describe the
      heterogeneity of molecular disorders in various human tumors and consider modern
      viewpoints of its development including genetic and non-genetic factors of
      heterogeneity origin and the role of cancer stem cells and clonal evolution. We
      also systematize data on the contribution of tumor diversity to progression of
      various tumors and the efficiency of their treatment. The main problems are
      indicated in the diagnosis and therapy of malignant tumors caused by intratumor
      heterogeneity and possible pathways for their solution. Moreover, we also suggest
      the key goals whose achievement promises to minimize the problem of intratumor
      heterogeneity and to identify new prognostic, predictive, and target markers for
      adequate and effective treatment of cancer. 

PMID- 24460936
TI  - Experimental and theoretical studies of mechanical unfolding of different
      proteins.
AB  - Mechanical properties of proteins are important for a wide range of biological
      processes including cell adhesion, muscle contraction, and protein translocation
      across biological membranes. It is necessary to reveal how proteins achieve their
      required mechanical stability under natural conditions in order to understand the
      biological processes and also to use the knowledge for constructing new
      biomaterials for medical and industrial purposes. In this connection, it is
      important to know how a protein will behave in response to various impacts.
      Theoretical and experimental works on mechanical unfolding of globular proteins
      will be considered in detail in this review. 

PMID- 24460938
TI  - Biological photoreceptors of light-dependent regulatory processes.
AB  - Progress in understanding primary mechanisms of light reception in
      photoregulatory processes is achieved through discovering new biological
      photoreceptors, chiefly the regulatory sensors of blue/UV-A light. Among them are
      LOV domain-containing proteins and DNA photolyase-like cryptochromes, which
      constitute two widespread groups of photoreceptors that use flavin cofactors (FMN
      or FAD) as the photoactive chromophores. Bacterial LOV domain modules are
      connected in photoreceptor proteins with regulatory domains such as diguanylate
      cyclases/phosphodiesterases, histidine kinases, and DNA-binding domains that are
      activated by photoconversions of flavin. Identification of red/far-red light
      sensors in chemotrophic bacteria (bacteriophytochromes) and crystal structures of
      their photosensor module with bilin chromophore are significant for decoding the
      mechanisms of phytochrome receptor photoconversion and early step mechanisms of
      phytochrome-mediated signaling. The only UV-B regulatory photon sensor, UVR8,
      recently identified in plants, unlike other photoreceptors functions without a
      prosthetic chromophore: tryptophans of the unique UVR8 protein structure provide
      a "UV-B antenna". Our analysis of new data on photosensory properties of the
      identified photoreceptors in conjunction with their structure opens insight on
      the influence of the molecular microenvironment on light-induced chromophore
      reactions, the mechanisms by which the photoactivated chromophores trigger
      conformational changes in the surrounding protein structure, and structural bases
      of propagation of these changes to the interacting effector domains/proteins. 

PMID- 24460937
TI  - Malignant melanoma and melanocortin 1 receptor.
AB  - The conventional chemotherapeutic treatment of malignant melanoma still remains
      poorly efficient in most cases. Thus the use of specific features of these tumors
      for development of new therapeutic modalities is highly needed. Melanocortin 1
      receptor (MC1R) overexpression on the cell surface of the vast majority of human
      melanomas, making MC1R a valuable marker of these tumors, is one of these
      features. Naturally, MC1R plays a key role in skin protection against damaging
      ultraviolet radiation by regulating eumelanin production. MC1R activation is
      involved in regulation of melanocyte cell division. This article reviews the
      peculiarities of regulation and expression of MC1R, melanocytes, and melanoma
      cells, along with the possible connection of MC1R with signaling pathways
      regulating proliferation of tumor cells. MC1R is a cell surface endocytic
      receptor, thus considered perspective for diagnostics and targeted drug delivery.
      A number of new therapeutic approaches that utilize MC1R, including
      endoradiotherapy with Auger electron and alpha- and beta-particle emitters,
      photodynamic therapy, and gene therapy are now being developed. 

PMID- 24460939
TI  - Selection of peptide inhibitors for double-stranded RNA-dependent protein kinase
      PKR.
AB  - Protein kinase inhibitors have been developed and applied as antitumor drugs. The
      majority of these inhibitors are derived from ATP analogs with limited
      specificity towards the kinase target. Here we present our proof-of-principle
      study on peptide inhibitors for kinases. Two peptides were selected by phage
      display against double-stranded RNA-dependent protein kinase (PKR). In vitro
      assay revealed that these peptides exhibit an inhibitory effect on PKR-catalyzed
      phosphorylation of the alpha subunit of eukaryotic initiation factor 2
      (eIF2alpha). The peptides also interrupt PKR activity in cells infected by
      viruses, as PKR activation is one of the hallmarks of host response to viral
      infection. Kinetic study revealed that one of the peptides, named P1, is a
      competitive inhibitor for PKR, while the other, named P2, exhibits a more
      complicated pattern of inhibition on PKR activity. Fragment-based docking of the
      PKR-peptide complex suggests that P1 occupies the substrate pocket of PKR and
      thus inhibits the binding between PKR and eIF2alpha, whereas P2 sits near the
      substrate pocket. The computational model of PKR-peptide complex agrees with
      their kinetic behavior. We surmise that peptide inhibitors for kinases have
      higher specificity than ATP analogs, and that they provide promising leads for
      the optimization of kinase inhibitors. 

PMID- 24460940
TI  - Bacterial and cell-free production of APP671-726 containing amyloid precursor
      protein transmembrane and metal-binding domains.
AB  - More than half of the mutations associated with familiar Alzheimer's disease have
      been found in the transmembrane domain of amyloid precursor protein (APP). These
      pathogenic mutations presumably influence the APP transmembrane domain structural
      and dynamic properties and result in its conformational change or/and lateral
      dimerization. Despite much data about the pathogenesis of Alzheimer's disease,
      the initial steps of the pathogenesis remain unclear so far. For the
      investigation of the molecular basis of Alzheimer's disease, we selected amyloid
      precursor protein fragment APP671-726 containing the transmembrane and metal
      binding domains. This fragment is the substrate of the gamma-secretase complex
      whose abnormal activity leads to the formation of amyloidogenic Abeta42 peptides.
      This work for the first time describes a highly effective cell-free APP671-726
      production method and improved method of bacterial synthesis. Both methods yield
      milligram quantities of isotope-labeled protein for structural study by high
      resolution NMR spectroscopy in membrane mimicking milieus. 

PMID- 24460942
TI  - Organotypic culture of neural retina as a research model of neurodegeneration of
      ganglion cells.
AB  - Organotypic models deserve special attention among the large variety of methods
      of vertebrate retina cultivation. The purpose of this study was to make a
      detailed qualitative and quantitative characterization of a model employing
      roller organotypic cultivation of the neural retina of rat eye posterior segment,
      with special attention to morphological and functional characteristics of retinal
      ganglion cells. The study included morphological analysis of retina histological
      preparations as well as estimation of RNA synthesis and evaluation of neuron
      survival by the Brachet and TUNEL methods, respectively. Retina has been shown to
      display normal morphofunctional characteristics for the first 12 h of
      cultivation. After 24 h, a substantial number of ganglion cells underwent
      pyknosis and stopped RNA synthesis. Almost all the cells of the retinal ganglion
      layer became apoptotic by 3-4 days in vitro. In the course of cultivation, neural
      retina is detached from the underlying layers of the posterior eye segment and
      undergoes significant cytoarchitectonic changes. The causes of ganglion cell
      death during organotypic cultivation of eye posterior segment are discussed. This
      method can serve as a suitable model for the screening of new retinoprotectors
      and for research on ganglion cell death resulting from retina degenerative
      diseases, e.g. glaucoma. 

PMID- 24460941
TI  - Functional and structural characterization of family 6 carbohydrate-binding
      module (CtCBM6A) of Clostridium thermocellum alpha-L-Arabinofuranosidase.
AB  - The gene encoding the family 6 carbohydrate-binding module (CtCBM6A) from
      Clostridium thermocellum, cloned in pET-21a(+) expression vector, was
      overexpressed using Escherichia coli BL-21(DE3) cells and purified by immobilized
      metal-ion affinity chromatography. SDS-PAGE analysis of the recombinant CtCBM6A
      showed molecular size of approximately 15 kDa. Ligand-binding analysis of CtCBM6A
      with rye arabinoxylan and oat spelt xylan by affinity gel electrophoresis showed
      low affinity for these ligands (Ka of 40 and 26 liter/g, respectively), and
      analysis by fluorescence spectroscopy (Ka of 33 and 15 liter/g, respectively)
      corroborated lower binding affinity with the above soluble ligands. However,
      CtCBM6A displayed significantly higher ligand-binding affinity with insoluble
      wheat arabinoxylan with equilibrium association constant Ka of 230 M(-1) and
      binding capacity (N0) of 11 umole/g. The protein melting curve of CtCBM6A
      displayed a peak shift from 53 to 58 degrees C in the presence of Ca2+,
      indicating that Ca2+ imparts thermal stability to the CtCBM6A structure. Homology
      modeling of CtCBM6A revealed a characteristic beta-sandwich core structure. The
      Ramachandran plot of CtCBM6A showed 89% of the residues in the most favorable
      region, 10% in additionally favored region, and 1% in generously allowed region,
      indicating that CtCBM6A has a stable conformation.

PMID- 24460943
TI  - Construction and functional analysis of novel dominant-negative mutant of human
      SOX18 protein.
AB  - SOX18 transcription factor plays important roles in a range of biological
      processes such as vasculogenesis, hair follicle development, lymphangiogenesis,
      atherosclerosis, and angiogenesis. In this paper we present the generation of a
      novel SOX18 dominant-negative mutant (SOX18DN) encoding truncated SOX18 protein
      that lacks a trans-activation domain. We show that both wild-type SOX18 (SOX18wt)
      and truncated human SOX18 proteins are able to bind to their consensus sequence
      in vitro. Functional analysis confirmed that SOX18wt has potent trans-activation
      properties, while SOX18DN displays dominant-negative effect. We believe that
      these SOX18wt and SOX18DN expression constructs could be successfully used for
      further characterization of the function of this protein. 

PMID- 24460944
TI  - Mitochondrial models of pathologies with oxidative stress. Efficiency of
      alkalization to reduce mitochondrial damage.
AB  - Previously, we developed a method to monitor the development of oxidative stress
      in isolated liver mitochondria. The method is based on recording of membrane
      potential changes in response to sequential introduction of low concentrations (5
      20 MUM) of tert-butyl hydroperoxide (tBHP). It allows monitoring of the extent of
      amplification or attenuation of oxidative stress caused by external influences
      (changes in incubation conditions, additions of biologically active substances).
      Based on this method, we created a mitochondrial model for the study and
      improvement of treatment of pathologies associated with oxidative stress. The
      following two processes were simulated in the experiments: 1) introduction of
      desferal for treatment of serious diseases caused by cell overload with iron
      (high desferal concentrations were shown to suppress mitochondrial energetics);
      2) efficiency of alkalization to reduce mitochondrial damage induced by oxidative
      stress. The experiments have shown that even a small increase in pH
      (alkalization) increases the amount of tBHP that can be added to mitochondria
      before the MPTP ("mitochondrial permeability transition pore") is induced. The
      effect of alkalization was shown to be close to the effect of cyclosporin A in
      the pH range 7.2-7.8. The mechanism of the similarities of these effects in the
      organism and in mitochondrial suspensions is explained by the increase in toxic
      reactive oxygen species in both systems under oxidative stress. 

PMID- 24460945
TI  - Identification of novel acyl-ACP thioesterase gene ClFATB1 from Cinnamomum
      longepaniculatum.
AB  - A putative fatty acyl-acyl carrier protein (acyl-ACP) thioesterase (thioesterase)
      full-length cDNA sequence named as ClFATB1 was obtained from the seed cDNA
      library of Cinnamomum longepaniculatum by the SMART-RACE method. The novel gene
      encodes a protein of 382 amino acid residues with close homology to fatty acid
      thioesterase type B (FATB) enzymes of other plants, with two essential residues
      (His285 and Cys320) for thioesterase catalytic activity. The gene was transcribed
      in all tissues of C. longepaniculatum, the highest being in seeds. Recombinant
      ClFATB1 in Escherichia coli had higher specific activities against saturated 16:0
      and 18:0-ACPs than on unsaturated 18:1-ACP. Overexpression of ClFATB1 in
      transgenic tobaccos upregulated thioesterase activities of crude proteins against
      16:0-ACP and 18:0-ACP by 20.3 and 5.7%, respectively, and resulted in an increase
      in the contents of palmitic and stearic acids by 15.4 and 10.5%, respectively.
      However, ectopic expression of this gene decreased the substrate specificities of
      crude proteins to unsaturated 18:1-ACP by 12.7% in transgenic tobacco and lowered
      the contents of oleic, linoleic, and linolenic acids in transgenic leaves. So
      ClFATB1 would potentially upregulate the synthesis of saturated fatty acids and
      downregulate unsaturated ones in the fatty acid synthesis pathway of plants. 

PMID- 24460946
TI  - Characterization and diagnostic evaluation of chronic polyneuropathies induced by
      oxaliplatin and docetaxel comparing skin biopsy to quantitative sensory testing
      and nerve conduction studies.
AB  - BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy negatively
      affects the quality of life for many patients treated with oxaliplatin or
      docetaxel for gastrointestinal cancer or breast cancer. Symptoms can persist long
      after treatment and often include neuropathic pain. Our objective was to
      characterize the neuropathies with regard to symptoms, neurological signs and
      objective evidence of damage to the structure and function of the peripheral
      nerves. Furthermore, the diagnostic values of skin biopsy, quantitative sensory
      testing (QST) and nerve conduction studies (NCS) were compared. METHODS: Patients
      complaining of neuropathy symptoms at least 3 months after completion of
      treatment with oxaliplatin (n = 20) or docetaxel (n = 20) were recruited from the
      Department of Oncology or using hospital records. Neuropathy scores were
      determined along with the intraepidermal nerve fibre density in skin biopsies
      from the proximal and distal parts of the leg, QST and NCS. RESULTS: Clinically
      only sensory functions were affected. In general, neuropathy scores were higher
      in the oxaliplatin-treated group. Both sensory and motor fibres were affected in
      the NCS, showing predominantly signs of axonal damage. Mechanical detection
      threshold was most often affected in the QST. NCS, QTS and skin biopsy were
      abnormal in 11, 13 and 17 and 7, 11 and 15 of the oxaliplatin-treated patients
      and docetaxel-treated patients, respectively. CONCLUSIONS: Chemotherapy-induced
      peripheral neuropathy after oxaliplatin or docetaxel treatment is a clinically
      sensory, axonal neuropathy affecting only small nerve fibres in some patients.
      NCS are often normal, whereas QST and skin biopsy have a higher diagnostic
      sensitivity.

PMID- 24460947
TI  - Impact of primer choice on characterization of orchid mycorrhizal communities
      using 454 pyrosequencing.
AB  - Although the number of studies investigating mycorrhizal associations in orchids
      has increased in recent years, the fungal communities associating with orchids
      and how they differ between species and sites remain unclear. Recent research has
      indicated that individual orchid plants may associate with several fungi
      concurrently, implying that to study mycorrhizal associations in orchids the
      fungal community should be assessed, rather than the presence of individual
      dominant fungal species or strains. High-throughput sequencing methods, such as
      454 pyrosequencing, are increasingly used as the primary tool for such analyses.
      However, many studies combine universal primers from previous phylogenetic or
      ecological studies to generate amplicons suitable for 454 pyrosequencing without
      first critically evaluating their performance, potentially resulting in biased
      fungal community descriptions. Here, following in silico primer analysis we
      evaluated the performance of different combinations of existing PCR primers to
      characterize orchid mycorrhizal communities using 454 pyrosequencing by analysis
      of both an artificially assembled community of mycorrhizal fungi isolated from
      diverse orchid species and root samples from three different orchid species
      (Anacamptis morio, Ophrys tenthredinifera and Serapias lingua). Our results
      indicate that primer pairs ITS3/ITS4OF and ITS86F/ITS4, targeting the internal
      transcribed spacer-2 (ITS-2) region, outperformed other tested primer pairs in
      terms of number of reads, number of operational taxonomic units recovered from
      the artificial community and number of different orchid mycorrhizal associating
      families detected in the orchid samples. Additionally, we show the complementary
      specificity of both primer pairs, making them highly suitable for tandem use when
      studying the diversity of orchid mycorrhizal communities. 

PMID- 24460948
TI  - An inorganic geochemical argument for coupled anaerobic oxidation of methane and
      iron reduction in marine sediments.
AB  - Here, we present results from sediments collected in the Argentine Basin, a non
      steady state depositional marine system characterized by abundant oxidized iron
      within methane-rich layers due to sediment reworking followed by rapid
      deposition. Our comprehensive inorganic data set shows that iron reduction in
      these sulfate and sulfide-depleted sediments is best explained by a microbially
      mediated process-implicating anaerobic oxidation of methane coupled to iron
      reduction (Fe-AOM) as the most likely major mechanism. Although important in many
      modern marine environments, iron-driven AOM may not consume similar amounts of
      methane compared with sulfate-dependent AOM. Nevertheless, it may have broad
      impact on the deep biosphere and dominate both iron and methane cycling in
      sulfate-lean marine settings. Fe-AOM might have been particularly relevant in the
      Archean ocean, >2.5 billion years ago, known for its production and accumulation
      of iron oxides (in iron formations) in a biosphere likely replete with methane
      but low in sulfate. Methane at that time was a critical greenhouse gas capable of
      sustaining a habitable climate under relatively low solar luminosity, and
      relationships to iron cycling may have impacted if not dominated methane loss
      from the biosphere. 

PMID- 24460949
TI  - Factors influencing work participation of adults with developmental dyslexia: a
      systematic review.
AB  - BACKGROUND: Evidence has been synthesized to determine hindering and facilitating
      factors associated with the work participation of adults with developmental
      dyslexia (DD), classified according to the International Classification of
      Functioning, Disability and Health (ICF). METHODS: A systematic literature review
      has been performed. Two search strings were used to determine the population and
      the context of work. The ICF was expanded with two subdivisions: one that made
      the environmental factors more work-related and a subdivision of personal
      factors. For data extraction the method known as qualitative metasummary was used
      and the manifest frequency effect size (MFES) for each category in the ICF was
      calculated. RESULTS: From 33 included studies 318 factors have been extracted and
      classified in the ICF. In the classification the frequency of occurrences and the
      consistency in direction (i.e., hindering or facilitating) have been made
      visible. The ICF categories with the highest MFES were mental functions with
      factors like feelings and emotions about dyslexia; activities like reading or
      writing/spelling; participation with factors like acquiring and keeping a job;
      social relationships at work where the attitudes and support of the employer and
      co-workers are important; working conditions with factors like the availability
      of assistive technology and accommodations on the job; and personal factors like
      self-disclosure and coping strategies. CONCLUSIONS: In the context of work DD
      affects nearly all domains of functioning, mostly in a negative way. Within each
      domain the impact of DD increases over the course of life. To overcome that
      negative influence, many forms of adaptation, compensation, or coping are
      mentioned. Also notable is the lack of positive attitudes toward DD of the
      participants with DD-with the exception of the attitudes of teachers with DD-as
      well as on the part of colleagues, supervisors, and employers.

PMID- 24460950
TI  - Effect of empathy trait on attention to faces: an event-related potential (ERP)
      study.
AB  - BACKGROUND: Empathy is deeply linked with the ability to adapt to human social
      environments. The present study investigated the relationship between the empathy
      trait and attention elicited by discriminating facial expressions. METHODS: Event
      related potentials were measured while 32 participants (17 men and 15 women)
      discriminated facial expressions (happy or angry) and colors of flowers (yellow
      or purple) under an oddball paradigm. The empathy trait of participants was
      measured using the Interpersonal Reactivity Index (Davis, 1980). RESULTS: The
      empathy trait correlated positively with both the early portion (300 to 600 ms
      after stimulus onset) and late portion (600 to 800 ms after stimulus onset) of
      late positive potential (LPP) amplitude elicited by faces, but not with LPP
      elicited by flowers. CONCLUSIONS: This result suggests that, compared to people
      with low empathy, people with high empathy pay more attention when discriminating
      facial expressions. The present study suggests that differences exist in methods
      of adapting to social environments between people with high and low empathy.

PMID- 24460951
TI  - Genetic determination of lipoprotein(a) and its association with cardiovascular
      disease: convenient does not always mean better.

PMID- 24460952
TI  - Insecticide resistance mechanisms associated with different environments in the
      malaria vector Anopheles gambiae: a case study in Tanzania.
AB  - BACKGROUND: Resistance of mosquitoes to insecticides is a growing concern in
      Africa. Since only a few insecticides are used for public health and limited
      development of new molecules is expected in the next decade, maintaining the
      efficacy of control programmes mostly relies on resistance management strategies.
      Developing such strategies requires a deep understanding of factors influencing
      resistance together with characterizing the mechanisms involved. Among factors
      likely to influence insecticide resistance in mosquitoes, agriculture and
      urbanization have been implicated but rarely studied in detail. The present study
      aimed at comparing insecticide resistance levels and associated mechanisms across
      multiple Anopheles gambiae sensu lato populations from different environments.
      METHODS: Nine populations were sampled in three areas of Tanzania showing
      contrasting agriculture activity, urbanization and usage of insecticides for
      vector control. Insecticide resistance levels were measured in larvae and adults
      through bioassays with deltamethrin, DDT and bendiocarb. The distribution of An.
      gambiae sub-species and pyrethroid target-site mutations (kdr) were investigated
      using molecular assays. A microarray approach was used for identifying
      transcription level variations associated to different environments and
      insecticide resistance. RESULTS: Elevated resistance levels to deltamethrin and
      DDT were identified in agriculture and urban areas as compared to the susceptible
      strain Kisumu. A significant correlation was found between adult deltamethrin
      resistance and agriculture activity. The subspecies Anopheles arabiensis was
      predominant with only few An. gambiae sensu stricto identified in the urban area
      of Dar es Salaam. The L1014S kdr mutation was detected at elevated frequency in
      An gambiae s.s. in the urban area but remains sporadic in An. arabiensis
      specimens. Microarrays identified 416 transcripts differentially expressed in any
      area versus the susceptible reference strain and supported the impact of
      agriculture on resistance mechanisms with multiple genes encoding pesticide
      targets, detoxification enzymes and proteins linked to neurotransmitter activity
      affected. In contrast, resistance mechanisms found in the urban area appeared
      more specific and more related to the use of insecticides for vector control.
      CONCLUSIONS: Overall, this study confirmed the role of the environment in shaping
      insecticide resistance in mosquitoes with a major impact of agriculture
      activities. Results are discussed in relation to resistance mechanisms and the
      optimization of resistance management strategies.

PMID- 24460953
TI  - Dissection of additive genetic variability for quantitative traits in chickens
      using SNP markers.
AB  - The aim of this study was to separate marked additive genetic variability for
      three quantitative traits in chickens into components associated with classes of
      minor allele frequency (MAF), individual chromosomes and marker density using the
      genomewide complex trait analysis (GCTA) approach. Data were from 1351 chickens
      measured for body weight (BW), ultrasound of breast muscle (BM) and hen house egg
      production (HHP), each bird with 354 364 SNP genotypes. Estimates of variance
      components show that SNPs on commercially available genotyping chips marked a
      large amount of genetic variability for all three traits. The estimated
      proportion of total variation tagged by all autosomal SNPs was 0.30 (SE 0.04) for
      BW, 0.33 (SE 0.04) for BM, and 0.19 (SE 0.05) for HHP. We found that a
      substantial proportion of this variation was explained by low frequency variants
      (MAF <0.20) for BW and BM, and variants with MAF 0.10-0.30 for HHP. The marked
      genetic variance explained by each chromosome was linearly related to its length
      (R(2) = 0.60) for BW and BM. However, for HHP, there was no linear relationship
      between estimates of variance and length of the chromosome (R(2) = 0.01). Our
      results suggest that the contribution of SNPs to marked additive genetic
      variability is dependent on the allele frequency spectrum. For the sample of
      birds analysed, it was found that increasing marker density beyond 100K SNPs did
      not capture additional additive genetic variance.

PMID- 24460954
TI  - Naturalistic change in nonclinical paranoid experiences.
AB  - BACKGROUND: Numerous studies have shown that paranoia is common in the
      nonclinical population; however, little research has examined whether nonclinical
      paranoid beliefs change over time, or considered potential reasons for change.
      AIMS: The aim of the present study was therefore to examine naturalistic change
      in nonclinical paranoid experiences. METHOD: 60 participants described an
      idiosyncratic experience of paranoia, including when it occurred, and rated their
      experience along four key belief dimensions: preoccupation, impact, distress and
      conviction. Participants provided two ratings for each dimension, retrospective
      recall at the time of the occurrence of the paranoid event, and again at the time
      of the interview. Participants were also asked to provide qualitative
      descriptions of reasons for change in belief dimensions. RESULTS: Participants
      described paranoid experiences that had occurred over a large timeframe (1 day-25
      years). Reductions across all four belief dimensions were found, and seven key
      themes emerged following qualitative analysis of the participants' reason for
      change in response to the paranoid event. CONCLUSIONS: The findings highlight a
      number of factors associated with reported naturalistic changes in belief
      dimensions of conviction, distress, preoccupation and impact, which might be
      useful in enhancing interventions for clinical and nonclinical paranoia, and in
      helping to build models to account for why people showing clear paranoid ideation
      do, or do not, go on to develop clinical paranoia.

PMID- 24460955
TI  - Understanding the social context of fatal road traffic collisions among young
      people: a qualitative analysis of narrative text in coroners' records.
AB  - BACKGROUND: Deaths and injuries on the road remain a major cause of premature
      death among young people across the world. Routinely collected data usually
      focuses on the mechanism of road traffic collisions and basic demographic data of
      those involved. This study aimed to supplement these routine sources with a
      thematic analysis of narrative text contained in coroners' records, to explore
      the wider social context in which collisions occur. METHODS: Thematic analysis of
      narrative text from Coroners' records, retrieved from thirty-four fatalities
      among young people (16-24 year olds) occurring as a result of thirty road traffic
      collisions in a rural county in the south of England over the period 2005-2010.
      RESULTS: Six key themes emerged: social driving, driving experience, interest in
      motor vehicles, driving behaviour, perception of driving ability, and emotional
      distress. Social driving (defined as a group of related behaviours including:
      driving as a social event in itself (i.e. without a pre-specified destination);
      driving to or from a social event; driving with accompanying passengers; driving
      late at night; driving where alcohol or drugs were a feature of the journey) was
      identified as a common feature across cases. CONCLUSIONS: Analysis of the wider
      social context in which road traffic collisions occur in young people can provide
      important information for understanding why collisions happen and developing
      targeted interventions to prevent them. It can complement routinely collected
      data, which often focuses on events immediately preceding a collision.
      Qualitative analysis of narrative text in coroner's records may provide a way of
      providing this type of information. These findings provide additional support for
      the case for Graduated Driver Licensing programmes to reduce collisions involving
      young people, and also suggest that road safety interventions need to take a more
      community development approach, recognising the importance of social context and
      focusing on social networks of young people.

PMID- 24460957
TI  - Do implicit evaluations reflect unconscious attitudes?
AB  - We extend Newell & Shanks' (N&S's) arguments to the question of whether implicit
      evaluations reflect unconscious attitudes. We argue that correspondence to
      explicit evaluations fails to meet the criteria of relevance and sensitivity.
      When awareness is measured adequately and in line with N&S's criteria, there is
      compelling evidence that people are consciously aware of their implicit
      evaluations. 

PMID- 24460956
TI  - The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy
      metabolism.
AB  - Vitamin C is an essential factor for neuronal function and survival, existing in
      two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid
      (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain
      cortical neurons. Moreover, we show that most intracellular AA was rapidly
      oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in
      reduced glutathione that was immediately followed by a spontaneous recovery. This
      transient decrease in glutathione oxidation was preceded by an increase in the
      rate of glucose oxidation through the pentose phosphate pathway (PPP), and a
      concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the
      activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the
      PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by
      neurons in a time- and dose-dependent manner. Thus, DHA is a novel modulator of
      neuronal energy metabolism by facilitating the utilization of glucose through the
      PPP for antioxidant purposes.

PMID- 24460959
TI  - Epidemiological Analysis of Influenza A Infection in Cambodian Pigs and
      Recommendations for Surveillance Strategies.
AB  - This study analysed the available data of seroprevalence to human influenza
      viruses in pigs in Cambodia using generalized linear mixed models in order to
      improve understanding of factors underlying the spread of human influenza viruses
      in Cambodian pigs. The associations between seroprevalence against seasonal H1N1
      influenza virus in pigs and the population density of humans and pigs were not
      significant. However, a positive association between anti-H3 antibodies in pigs
      and the human population density was identified. In contrast, there was a
      negative association between seroprevalence of H3N2 in pigs and the pig
      population density. Our study has highlighted the difficulty in identifying
      epidemiological risk factors when a limited data set is used for analyses. We
      therefore provide recommendations on data collection for future epidemiological
      analyses that could be improved by collecting metadata related to the animals
      sampled. In addition, serosurveillance for influenza A viruses in pigs in high
      risk areas or at slaughterhouses is recommended in resource-limited countries. 

PMID- 24460958
TI  - Cardiac gating calibration by the Septal Scout for magnetic resonance coronary
      angiography.
AB  - BACKGROUND: Electrocardiogram (ECG) gating is commonly used to synchronize
      imaging windows to diastasis periods over multiple heartbeats in magnetic
      resonance (MR) coronary angiography. Calibration of the ECG gating parameters is
      typically based on a cine cardiovascular MR (CMR) video of the beating heart.
      Insufficient temporal resolution in the cine-CMR method, however, may produce
      gating errors and motion artifacts.It was previously shown that tissue Doppler
      echocardiography (TDE) can identify accurate diastasis window timings by
      observing the movement of the interventricular septum (IVS). We present a new CMR
      technique, the Septal Scout, for measuring IVS motion. We demonstrate that
      cardiac gating windows determined by the Septal Scout produce sharper coronary MR
      angiography images than windows determined by cine-CMR. METHODS: 9 healthy
      volunteers were scanned on a GE Optima 450w 1.5T MR system. Cine-CMR was acquired
      and used to identify the start and end times of the diastasis window (Wcine). The
      Septal Scout employs a one-dimensional steady-state free precession (SSFP)
      readout along the ventricular septum prescribed from the 4-chamber view. The
      Septal Scout data is processed to produce a septal velocity function, from which
      the diastasis window was determined (Wsep). Non-contrast-enhanced MR angiography
      was performed twice for each volunteer: once gated to Wcine, once to Wsep. Vessel
      sharpness was assessed subjectively by two experienced observers, and
      quantitatively by full width half maximum (FWHM) measurements of cross-sectional
      vessel profiles. In addition, TDE was performed on a subcohort of 6 volunteers
      where diastasis windows (WTDE) were determined from the IVS velocity measured in
      the 4-chamber view. Wsep and WTDE were compared using Pearson's correlation.
      RESULTS: MRA acquisitions were successful in all volunteers. Vessel segments
      produced smaller FWHM measurements and were deemed sharper when imaged during the
      Septal Scout gating windows (p < 0.05). Subjective assessment of sharpness also
      improved for the Septal Scout-gated scans (p < 0.01 for both observers). Lastly,
      Wsep and WTDE were highly correlated (R > 0.98, p < 0.001). CONCLUSIONS: The MR
      Septal Scout technique was introduced and demonstrated to be more accurate at
      determining cardiac gating windows than cine-CMR, yielding sharper coronary MR
      angiography images.

PMID- 24460960
TI  - Expression of 14-3-3 sigma, cyclin-dependent kinases 2 and 4, p16, and Epstein
      Barr nuclear antigen 1 in nasopharyngeal carcinoma.
AB  - OBJECTIVE: The protein 14-3-3 sigma plays a role in cell cycle arrest by
      sequestering cyclin-dependent kinase 1 cyclin B1 complexes, as well as cyclin
      dependent kinases 2 and 4, hence its definition as a cyclin-dependent kinase
      inhibitor. However, the nature of the interaction between these biological
      markers in nasopharyngeal carcinoma is unknown. This study aimed to investigate
      whether altered expression of these markers contributes to nasopharyngeal
      carcinogenesis. METHODS: The study population consisted of 30 nasopharyngeal
      carcinoma patients and 10 patients without nasopharyngeal carcinoma. The
      nasopharyngeal carcinoma cell lines TW02, TW04 and Hone-1 were also assessed. We
      analysed levels of messenger RNA and protein for the p16 gene and the 14-3-3
      sigma, Epstein-Barr nuclear antigen 1, and cyclin-dependent kinase 2 and 4
      proteins, in nasopharyngeal carcinoma tissue specimens and cell lines and in
      normal nasopharyngeal tissue. RESULTS: Protein and messenger RNA levels for
      cyclin-dependent kinase 2 and Epstein-Barr nuclear antigen 1 were significantly
      higher in nasopharyngeal carcinoma compared with normal tissue, while levels of
      cyclin-dependent kinase 4 generally were not; results for 14-3-3 sigma varied.
      Nasopharyngeal carcinoma patients had diminished p16 gene expression, compared
      with normal tissue. CONCLUSION: Levels of cyclin-dependent kinase 2 and Epstein
      Barr nuclear antigen 1 were significantly higher in nasopharyngeal carcinoma than
      in normal tissue, while p16 gene expression was diminished. These three proteins
      may contribute to nasopharyngeal carcinogenesis.

PMID- 24460961
TI  - Antimicrobial resistance and toxin gene profiles of Staphylococcus aureus strains
      from Holstein milk.
AB  - Isolation of Staphylococcus aureus (Staph. aureus) from Holstein milk samples
      with mastitis and nonmastitis was conducted to estimate its prevalence,
      antimicrobial resistance and toxin genes. A total of 353 milk samples were
      collected from three Chinese Holstein herds. Fifty-three Staph. aureus isolates
      collected from 29 Staph. aureus-positive samples were characterized via
      antimicrobial susceptibility, toxin genes and Pulsed-field Gel Electrophoresis
      (PFGE) profiles. The prevalence of Staph. aureus was 4.0-9.5% in mastitic and 7.3
      11.5% in nonmastitic samples in the analysed herds. Approximately 61.0% of Staph.
      aureus strains isolated from mastitis cows were resistant to >=10 antimicrobials
      compared with 0% of isolates with nonmastitis. The most frequently observed super
      antigenic toxin gene was pvl (41.5%) followed by seh + pvl (13.2%). We did not
      find mecA-positive methicillin-resistant Staph. aureus (MRSA) strains, while mecA
      negative MRSA strains were identified in the three herds. PFGE results suggested
      potential transmission of Staph. aureus strains in different farms. These results
      open new insights into Staph. aureus transmission and antimicrobial resistance of
      Holstein dairy cows and into developing strategies for udder health improvement
      of dairy cattle. SIGNIFICANCE AND IMPACT OF THE STUDY: Significantly higher
      levels of antibiotic resistance of Staphylococcus aureus strains were detected in
      the lactating Holstein milk with clinical mastitis compared with that without
      clinical mastitis. PFGE results suggest potential transmission of Staph. aureus
      strains in different dairy farms. The results imply that the dairy farms need to
      select effective antibiotics in the treatment of Staph. aureus-infected cows and
      prevent the transmission of Staph. aureus strains from one herd to another.

PMID- 24460963
TI  - Environmental and capacity requirements are critical for implementing and
      sustaining a drug prevention program: a multiple case study of "Clubs against
      drugs".
AB  - BACKGROUND: "Clubs against drugs" (CAD) is a comprehensive program with a systems
      approach to prevention with the intention of preventing drug use in nightclub
      environment. In 2001 CAD was developed and implemented in Stockholm and was
      disseminated to 20 other municipalities in Sweden up until 2010. This study
      investigates the factors related to the implementation and compares Stockholm to
      the rest of the municipalities. METHODS: A sequential exploratory method was used
      which consisted of three steps including a questionnaire and two rounds of
      interviews. Questionnaires included all communities and the interviews included
      twelve respondents from three example municipalities in the first phase and four
      respondents from Stockholm in the second phase. The interviews were analyzed
      using content analysis. RESULTS: In Stockholm the program was described as having
      been implemented and sustained over time. The implementation in the example
      municipalities was perceived as difficult with many obstacles and achieving
      sustainability was also described as difficult. Two of three municipalities were
      not active at the time of this study, illustrating that the program only lasted a
      few years. Factors identified as being related to implementation outcomes were
      need assessments, participation, support, collaboration and local enthusiasts.
      CONCLUSIONS: The capacity to implement and sustain CAD differed substantially
      between Stockholm and the other municipalities. If the prerequisites and capacity
      are not sufficient the implementation is not likely to be successful, even when
      the activities are promoted on a national level like CAD. The needs of the
      interventions and the capacity to implement the program should be examined before
      adopting the program. This was not done, probably because the drive to spread the
      activity was not sufficiently questioned.

PMID- 24460964
TI  - The accuracy of the Child and Adolescent Intellectual Disability Screening
      Questionnaire (CAIDS-Q) in classifying severity of impairment: a brief report.
AB  - BACKGROUND: Severity of intellectual disability (ID) is associated with a range
      of outcomes for the individual and having an indication of severity can help
      inform support needs. Previous research has not evaluated whether screening tools
      can accurately ascertain severity category in addition to providing a red flag
      for the presence of ID. METHODS: We used multi-category receiver operating
      characteristic (ROC) analysis to assess whether the Child and Adolescent
      Intellectual Disability Screening Questionnaire (CAIDS-Q) could be used
      clinically to classify individuals (n = 191) aged between 12 and 18 according to
      British Psychological Society (BPS) categories of severity of impairment.
      RESULTS: The volume under the surface statistic (VUS) was 0.59. The optimal cut
      points estimated based on the ROC surface and Youden Index provided correct
      classification probabilities for the severe, significant and non-ID groups of
      0.44, 0.63 and 0.86 and 0.79, 0.29 and 0.88 respectively. CONCLUSIONS: While the
      CAIDS-Q can accurately discriminate between those with and without ID, and
      provides a heuristic for severity of ID, the results indicate that it does not
      reliably identify whether an individual falls into the severe or significant
      category of intellectual impairment.

PMID- 24460965
TI  - Polyreactivity of natural antibodies: exchange by HL-fragments.
AB  - The polyreactivity of binding (formation of antibody (AB) complexes not only with
      specific but also with foreign antigens) is a widespread phenomenon that in some
      cases can be caused by a conformational lability of the antigen-binding sites of
      antibodies (which increases upon treatment with various destabilizing agents) and
      leads to AB binding with very different antigens. Some ABs exist as dimers of the
      initial ABs and their idiotypes (or anti-idiotypes) capable of producing
      intramolecular cyclic complexes with features of polyreactants. Another mechanism
      of binding polyreactivity is an exchange in blood by halves of IgG4 molecules (HL
      fragments) against various antigens. Also, for the first time catalytic
      polyfunctionality of human milk ABs has been detected, which is caused by an
      exchange by HL-fragments between molecules of lambda- and kappa-IgG (IgG1-IgG4)
      and also by lambda- and kappa-sIgA against different antigens with formation of
      very different chimeric antibodies. This review considers all possible pathways
      of formation of polyspecific immunoglobulins and their biological functions
      described in the literature, as well as mechanisms of binding polyreactivity and
      catalytic polyfunctionality of natural antibodies. 

PMID- 24460966
TI  - Protein apparatus for horizontal transfer of agrobacterial T-DNA to eukaryotic
      cells.
AB  - This review analyzes agrobacterial virulence proteins and recipient cell proteins
      involved in horizontal transfer of a T-DNA-protein complex. Specifically, it
      considers the early stages of the interactions of partners (signal exchange,
      attachment, close contact); T-DNA release from bacterial cells; channel formation
      for the transfer of ssDNA between the partners; transfer of agrobacterial T-DNA
      through the membrane, cytoplasm, and nuclear membrane of the recipient cell and
      its incorporation into the recipient cell genome. It further discusses possible
      pathways of agrobacterial ssDNA transfer to the recipient cells. In particular,
      the possible role of T-pili and VirE2 protein during conjugative transfer of
      agrobacterial ssDNA between donor and recipient cells is discussed. 

PMID- 24460967
TI  - Human leptin triggers proliferation of A549 cells via blocking endoplasmic
      reticulum stress-related apoptosis.
AB  - Lung cancer is a disease characterized by uncontrolled cell growth in tissues of
      the lung. Leptin is a pleiotropic hormone with antiapoptotic and proliferative
      roles involved in several systems. However, there is no known antiapoptotic
      mechanism of leptin in non-small cell lung cancer (NSCLC). So, we investigated
      the antiapoptotic mechanism of leptin in NSCLC. Proliferation, apoptosis, and the
      specific mechanism of leptin-transfected cells were analyzed in this study.
      Leptin, p-Perk, IRE1, cleaved ATF6, spliced XBP1, eIF2-alpha, TRAF2, CHOP, and
      caspase 12 proteins were detected by Western blot, and endoplasmic reticulum (ER)
      stress-related mRNA was detected by semi-quantitative reverse transcription PCR
      (RT-PCR). Leptin in A549 and transfected cells inhibited cisplatin-activated ER
      stress-associated mRNA transcription and activation of proteins. ER stress
      unfolded protein response (UPR) proteins, PERK and ATF6, were involved in leptin
      triggered apoptosis. XBP1 and TRAF2 were increased significantly when treated
      with cisplatin in A549-siLPT and non-transfected cells. CHOP expression was
      blocked in A549 and transfected cells (LPT-PeP and LPT-EX cells). In conclusion,
      leptin can promote the proliferation of A549 cells through blocking ER stress
      mediated apoptosis. This blocking is mediated by the p-Perk and ATF6 pathway
      through blocking activation of CHOP. 

PMID- 24460969
TI  - Internal initiation of polyuridylic acid translation in bacterial cell-free
      system.
AB  - The task of the present work was to answer the question: is the free 5'-end
      needed for effective translation of a model polyribonucleotide template -
      polyuridylic acid - in a bacterial (E. coli) cell-free system? For this purpose,
      the template activities of the original polyuridylic acid with its free 5'-end
      and the polyuridylic acid with blocked 5'-end were compared in the bacterial cell
      free translation system. To block the 5'-end, the cytidylic
      oligodeoxyribonucleotide with fluorescein residue at its 5'-end and uridylic
      oligoribonucleotide sequence at its 3'-end, schematically described as
      FAM(dC)10(rU)50, was covalently attached (ligated) to the 5'-end of the template
      polyuridylic acid. It was shown that the efficiency of polyphenylalanine
      synthesis on the 5'-blocked template and on the polyuridylic acid with free 5'
      end was virtually the same. It was concluded that bacterial ribosomes are capable
      of effectively initiating translation at the polyuridylic sequence independently
      of the 5'-end of template polyribonucleotide, i.e. via an internal initiation
      mechanism, in the absence of a Shine-Dalgarno sequence and AUG start codon.

PMID- 24460968
TI  - Effect of sex hormones on levels of mRNAs coding for proteins involved in lipid
      metabolism in macrophages.
AB  - The effects of sex hormones estradiol (E2), testosterone (Te), and 5alpha
      dihydrotestosterone (DT) on cholesterol accumulation induced by modified low
      density lipoproteins (LDL) in macrophages differentiated from human peripheral
      blood monocytes and on the levels of mRNAs coding for proteins involved in lipid
      metabolism have been studied. All three hormones at physiological concentrations
      (1 nM) are capable of reducing cholesterol accumulation in cells. The treatment
      of cells with modified and native (not inducing cholesterol accumulation) LDL
      results in similar alterations in the expression of several mRNAs aimed primarily
      at homeostatic regulation of lipid metabolism. These alterations depend on the
      sex of macrophage donors and in some cases are even reversed in cells obtained
      from male and female donors. The cells not treated with modified LDL have no
      significant gender differences in the expression of the examined mRNAs. Hormones,
      either independently or in combination with the modified LDL, influence the
      levels of some mRNAs, and each hormone shows an individual range of effects.
      Correlation analysis of changes in mRNA content in the cells showed that the
      hormones may interfere with coordination of gene expression. Hormone action leads
      to: (1) reduced coupling of the content of individual mRNAs with their initial
      levels in the control cells; (2) reduced coupling of different mRNA levels; (3)
      regrouping of mRNAs between the clusters; and (4) changes in the number of
      factors that determine the correlation links between mRNAs. The data show that
      sex hormones may have impact on the level of expression of certain genes and, in
      particular, on the coordination of gene expression in macrophages.

PMID- 24460970
TI  - Reconstruction of absolute absorption spectrum of reduced heme a in cytochrome C
      oxidase from bovine heart.
AB  - This paper presents a new experimental approach for determining the individual
      optical characteristics of reduced heme a in bovine heart cytochrome c oxidase
      starting from a small selective shift of the heme a absorption spectrum induced
      by calcium ions. The difference spectrum induced by Ca2+ corresponds actually to
      a first derivative (differential) of the heme a(2+) absolute absorption spectrum.
      Such an absolute spectrum was obtained for the mixed-valence cyanide complex of
      cytochrome oxidase (a(2+)a3(3+)-CN) and was subsequently used as a basis spectrum
      for further procession and modeling. The individual absorption spectrum of the
      reduced heme a in the Soret region was reconstructed as the integral of the
      difference spectrum induced by addition of Ca2+. The spectrum of heme a(2+) in
      the Soret region obtained in this way is characterized by a peak with a maximum
      at 447 nm and half-width of 17 nm and can be decomposed into two Gaussians with
      maxima at 442 and 451 nm and half-widths of ~10 nm (589 cm(-1)) corresponding to
      the perpendicularly oriented electronic pi->pi* transitions B0x and B0y in the
      porphyrin ring. The reconstructed spectrum in the Soret band differs
      significantly from the "classical" absorption spectrum of heme a(2+) originally
      described by Vanneste (Vanneste, W. H. (1966) Biochemistry, 65, 838-848). The
      differences indicate that the overall gamma-band of heme a(2+) in cytochrome
      oxidase contains in addition to the B0x and B0y transitions extra components that
      are not sensitive to calcium ions, or, alternatively, that the Vanneste's
      spectrum of heme a(2+) contains significant contribution from heme a3(2+). The
      reconstructed absorption band of heme a(2+) in the alpha-band with maximum at 605
      nm and half-width of 18 nm (850 cm(-1)) corresponds most likely to the individual
      Q0y transition of heme a, whereas the Q0x transition contributes only weakly to
      the spectrum.

PMID- 24460971
TI  - SkBQ - prooxidant addressed to mitochondria.
AB  - Oxidative stress and mitochondrial dysfunction are the key links in the chain of
      development of pathologies associated with the violation of cellular energy
      metabolism. Development of mitochondria-addressed compounds highly specific for
      chemical processes is one of the most promising ways to develop approaches to the
      treatment of inherited and age-related diseases with mitochondrial etiology.
      Correlation of structure and chemical activity of the test compounds from a class
      of lipophilic cations revealed the key role of substituents in the aromatic ring
      of 1,4-benzoquinones in the manifestation of high antioxidant properties. In this
      work, it is shown that a synthesized benzoquinone derivative conjugated in
      position 6 with membrane-penetrating cation of decyltriphenylphosphonium and with
      substituents at position 2, 3, and 5 (SkBQ) has much lower antioxidant and
      significantly higher prooxidant activity in comparison with similar derivatives
      of plasto- and toluquinone SkQ1 and SkQT1 in experiments on isolated
      mitochondria. At the same time, SkBQ, like SkQ1 and SkQT1, can be reduced by the
      respiratory chain in the center i of complex III and decrease the mitochondrial
      membrane potential. In cell cultures of human fibroblasts, it was revealed that
      SkBQ does not protect cells from apoptosis induced by hydrogen peroxide. Under
      the same conditions, SkQ1 and SkQT1 exhibit a powerful protective effect. Thus,
      SkBQ can be seen as a mitochondria-addressed prooxidant. The possibility of using
      SkBQ as an anticancer drug for the treatment of cancers such as prostate cancer
      whose cells are sensitive to mitochondrial reactive oxygen species is discussed. 

PMID- 24460972
TI  - Do YB2/0 cells produce alien sugars?
AB  - Olovnikova et al. ("Impact on N-glycosylation profile of monoclonal anti-D
      antibodies as a way to control their immunoregulatory and cytotoxic properties"
      (2012) Biochemistry (Moscow), 77, 925-933) mentioned the presence of "alien
      sugars" on monoclonal antibodies (mAbs) produced by YB2/0 cell line. We summarize
      in this paper our previous findings on the glycosylation profile of two anti-D
      mAbs produced in this cell line (LFB-R297 and LFB-R593, so-called Roledumab). Our
      results show the absence of any immunogenic glycotopes, and furthermore neither
      immunogenicity nor other serious adverse reactions were observed during clinical
      trials. 

PMID- 24460973
TI  - Is an expression system for producing therapeutic antibodies with
      immunosuppressive properties found at last? Comment to letter by Dr. Quagliaroli.
AB  - The prophylaxis of the hemolytic disease of the newborn - a mandatory procedure
      in obstetrics - requires significant amounts of plasma-derived polyclonal anti-D
      immunoglobulin. Despite numerous attempts, the proper technology for mass
      production of effective monoclonal anti-D is still not available. LFB
      Biotechnologies is currently performing clinical trials with recombinant anti-D
      antibody that has low fucose content and is expressed in the cells of rat myeloma
      YB2/0. It was shown that this drug is well tolerated, accelerates fast clearance
      of D+ red blood cells, and can inhibit anti-D immune response in Rhesus-negative
      volunteers.

PMID- 24460974
TI  - Implementation of smoking cessation guidelines in the emergency department: a
      qualitative study of staff perceptions.
AB  - BACKGROUND: The US Public Health Service smoking cessation practice guideline
      specifically recommends that physicians and nurses strongly advise their patients
      who use tobacco to quit, but the best approach for attaining this goal in the
      emergency department (ED) remains unknown. The aim of this study was to
      characterize emergency physicians' (EPs) and nurses' (ENs) perceptions of
      cessation counseling and to identify barriers and facilitators to implementation
      of the 5 A's framework (Ask-Advise-Assess-Assist-Arrange) in the ED. METHODS: We
      conducted semi-structured, face-to-face interviews of 11 EPs and 19 ENs following
      a pre-post implementation trial of smoking cessation guidelines in two study EDs.
      We used purposeful sampling to target EPs and ENs with different attitudes toward
      cessation counseling, based on their responses to a written survey (Decisional
      Balance Questionnaire). Conventional content analysis was used to inductively
      characterize the issues raised by study participants and to construct a coding
      structure, which was then applied to study transcripts. RESULTS: The main
      findings of this study converged upon three overarching domains: 1) reactions to
      the intervention; 2) perceptions of patients' receptivity to cessation
      counseling; and 3) perspectives on ED cessation counseling and preventive care.
      ED staff expressed ambivalence toward the implementation of smoking cessation
      guidelines. Both ENs and EPs agreed that the delivery of smoking cessation
      counseling is important, but that it is not always practical in the ED on account
      of time constraints, the competing demands of acute care, and resistance from
      patients. Participants also called attention to the need for improved role
      clarity and teamwork when implementing the 5 A's in the ED. CONCLUSIONS: There
      are numerous challenges to the implementation of smoking cessation guidelines in
      the ED. ENs are generally willing to take the lead in offering brief cessation
      counseling, but their efforts need to be reinforced by EPs. ED systems need to
      address workflow, teamwork, and practice policies that facilitate prescription of
      smoking cessation medication, referral for cessation counseling, and follow-up in
      primary care. The results of this qualitative evaluation can be used to guide the
      design of future ED intervention studies. TRIAL REGISTRATION: ClinicalTrials.gov
      registration number NCT00756704.

PMID- 24460975
TI  - A comparison of three techniques (local anesthetic deposited circumferential to
      vs. above vs. below the nerve) for ultrasound guided femoral nerve block.
AB  - BACKGROUND: Fractured neck of femur generally requires operative fixation and is
      a common cause of admission to hospital. The combination of femoral nerve block
      and spinal anesthesia is a common anesthetic technique used to facilitate the
      surgical procedure. The optimal disposition of local anesthetic (LA) relative the
      femoral nerve (FN) has not been defined. Our hypothesis was: that the deposition
      of LA relative to the FN influences the quality of analgesia for positioning of
      the patient for performance of spinal anesthesia. The primary outcome was verbal
      rating (VRS) pain scores 0-10 assessed immediately after positioning the patient
      to perform spinal anesthesia. METHODS: With Institutional ethical approval and
      having obtained written informed consent from each, 52 patients were studied. The
      study was registered with ClinicalTrials.gov (NCT01527812). Patients were
      randomly allocated to undergo to one of three groups namely: intention to deposit
      lidocaine 2% (15 ml) i. above (Group A), ii. below (Group B), iii.
      circumferential (Group C) to the FN. A blinded observer assessed i. the sensory
      nerve block (cold) in the areas of the terminal branches of the FN and ii. VRS
      pain scores on passive movement from block completion at 5 minutes intervals for
      30 minutes. Immediately after positioning the patient for spinal anesthesia, VRS
      pain scores were recorded. RESULTS: Pain VRS scores during positioning were
      similar in the three groups [Above group/Below group/Circumferential group: 2(0
      9)/0(0-10)/3(0-10), median(range), p:0.32]. The block was deemed to have failed
      in 20%, 47% and 12% in the Above group, Below group and Circumferential group
      respectively. The median number of needle passes was greater in the
      Circumferential group compared with the Above group (p:0.009). Patient
      satisfaction was greatest in the Circumferential group [mean satisfaction scores
      were 83.5(19.8)/88.1(20.5)/93.8(12.3), [mean(SD), p=0.04] in the Above, Below and
      Circumferential groups respectively. CONCLUSIONS: We conclude that there is no
      clinical advantage to attempting to deposit LA circumferential to the femoral
      nerve (relative to depositing LA either above or below the nerve), during femoral
      nerve block in this setting.

PMID- 24460976
TI  - Multiple murine BRaf(V600E) melanoma cell lines with sensitivity to PLX4032.

PMID- 24460977
TI  - FKBP51 increases the tumour-promoter potential of TGF-beta.
AB  - BACKGROUND: FKBP51 (FKBP5 Official Symbol) is a large molecular weight component
      of the family of FK506 binding proteins (FKBP). In recent years, research studies
      from our laboratory highlighted functions for FKBP51 in the control of apoptosis
      and melanoma progression. FKBP51 expression correlated with the invasiveness and
      aggressiveness of melanoma. Since a role for TGF-beta in the enhanced tumorigenic
      potential of melanoma cells is widely described, we hypothesized a cooperative
      effect between FKBP51 and TGF-beta in melanoma progression. METHODS: SAN and A375
      melanoma cell lines were utilized for this study. Balb/c IL2gamma NOD SCID served
      to assess the ability to colonize organs and metastasize of different cell lines,
      which was evaluated by in vivo imaging. Realtime PCR and western blot served for
      measurement of mRNA and protein expression, respectively. RESULTS: By comparing
      the metastatic potential of two melanoma cell lines, namely A375 and SAN, we
      confirmed that an increased capability to colonize murine organs was associated
      with increased levels of FKBP51. A375 melanoma cell line expressed FKBP51 mRNA
      levels 30-fold higher in comparison to the SAN mRNA level and appeared more
      aggressive than SAN melanoma cell line in an experimental metastasis model. In
      addition, A375 expressed, more abundantly than SAN, the TGF-beta and the pro
      angiogenic TGF-beta receptor type III (TbetaRIII) factors. FKBP51 silencing
      produced a reduction of TGF-beta and TbetaRIII gene expression in A375 cell line,
      in accordance with previous studies. We found that the inducing effect of TGF
      beta on Sparc and Vimentin expression was impaired in condition of FKBP51
      depletion, suggesting that FKBP51 is an important cofactor in the TGF-beta
      signal. Such a hypothesis was supported by co immunoprecipitation assays, showing
      that FKBP51 interacted with either Smad2,3 and p300. In normal melanocytes,
      FKBP51 potentiated the effect of TGF-beta on N-cadherin expression and conferred
      a mesenchymal-like morphology to such round-shaped cells. CONCLUSIONS: Overall,
      our findings show that FKBP51 enhances some pro oncogenic functions of TGF-beta,
      suggesting that FKBP51-overexpression may help melanoma to take advantage of the
      tumor promoting activities of the cytokine.

PMID- 24460978
TI  - Genetics of Parkinson's disease: alpha-synuclein and other insights from Greece.

PMID- 24460979
TI  - SAwSu: an integrated model of associative and reinforcement learning.
AB  - Successfully explaining and replicating the complexity and generality of human
      and animal learning will require the integration of a variety of learning
      mechanisms. Here, we introduce a computational model which integrates associative
      learning (AL) and reinforcement learning (RL). We contrast the integrated model
      with standalone AL and RL models in three simulation studies. First, a synthetic
      grid-navigation task is employed to highlight performance advantages for the
      integrated model in an environment where the reward structure is both diverse and
      dynamic. The second and third simulations contrast the performances of the three
      models in behavioral experiments, demonstrating advantages for the integrated
      model in accounting for behavioral data. 

PMID- 24460981
TI  - Skatole metabolism in the pigs with reduced testicular oestrogen synthesis.
AB  - The objectives of the study were to investigate the involvement of oestrogens in
      the regulation of skatole levels in pigs. In total, 44 intact male pigs, siblings
      from 10 litters, were included in the study. Pigs were orally treated weekly with
      either 0.1 mg letrozole/kg body weight to reduce endogenous oestrogens or the
      canola oil vehicle. Fat and liver samples were collected at slaughter at 16, 20
      and 40 weeks of age. Skatole and androstenone levels in fat and activities of
      hepatic cytochrome P4501A1, CYP1A2, CYP2A19 and CYP2E1 were analysed. Letrozole
      treatment did not significantly change either the levels of skatole or activities
      of skatole-metabolising enzymes, suggesting that oestrogens are not responsible
      for gender-related differences in skatole concentrations in porcine tissues.

PMID- 24460980
TI  - Changes to memory structures in children treated for posterior fossa tumors.
AB  - Children treated for medulloblastoma (MB) exhibit long-term impairments in
      declarative memory, but the pathophysiology underlying this is unclear. Previous
      studies report declines in global white matter volume, but have failed to link
      this to declines in memory performance. We examined the effects of treatment on
      measures of global brain structure (i.e., total white and gray matter volume) and
      specific memory structures (i.e., hippocampus and uncinate fasciculus). We used
      volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one
      survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and
      healthy controls (n = 13). Compared to controls, the survivor group exhibited
      reduced white matter volume, damage to the uncinate fasciculus, and a smaller
      right hippocampus. Critically, reduced hippocampal volume was not related to
      differences in brain volume, suggesting that the hippocampus may be especially
      vulnerable to treatment effects. A subset of the survivors (n = 10) also
      underwent memory testing using the Children's Memory Scale (CMS). Performance on
      the general index of the CMS was significantly correlated with measures of
      hippocampal volume and uncinate fasciculus. The examination of treatment effects
      on specific brain regions provides a better understanding of long-term cognitive
      outcome in children with brain tumors, particularly medulloblastoma.

PMID- 24460982
TI  - Malaria in overseas labourers returning to China: an analysis of imported malaria
      in Jiangsu Province, 2001-2011.
AB  - BACKGROUND: While great success in malaria control has been achieved in China,
      imported malaria has become a major challenge in the context of malaria
      elimination. This retrospective study describes the epidemiological profile of
      imported malaria and identifies the at-risk population during the period of 2001
      2011 in Jiangsu Province. METHODS: Data on imported malaria cases in Jiangsu
      Province from 2001 to 2011 were collected from the infectious disease
      surveillance system and case investigation reports. Epidemiological trends were
      described and correlations between trends in exported labour and malaria imported
      from other countries were explored. RESULTS: From 2001 to 2011, 918 malaria cases
      and six malaria deaths were due to malaria imported from other countries,
      accounting for 12.4% of all malaria cases and 100% of all malaria deaths. During
      this time period the annual number of indigenous cases decreased from 1,163 to 13
      while the number of imported cases increased from 86 to 366. The relative
      proportion of cases imported from other countries versus other provinces also
      increased from 0.0% (0/86) to 97.0% (350/361). The most affected demographic
      groups were males (897 cases, 97.7%) and adults (20-50 years old: 857 cases,
      93.4%). All 918 cases had a recent travel history to malaria-endemic areas and
      the main purpose for travel was overseas labour (848 cases, 92.4%). The cases
      were mainly acquired from African countries (855 cases, 93.1%). Plasmodium
      falciparum was the most common species (733 cases, 79.8%). The increase in
      malaria cases imported from other countries was associated with the growth of
      investment to Africa from Jiangsu (R2 = 0.8057) and the increasing number of
      exported labourers to Africa from Jiangsu (R2 = 0.8863). CONCLUSIONS: From 2001
      to 2011 in Jiangsu Province, there was a consistent increase in the number of
      malaria cases imported from other countries while the number of locally acquired
      cases sharply declined. This trend may be ascribed to the increasing investment
      from China to Africa and the rising number of Chinese labourers working in
      Africa. Preventative efforts should be targeted to this high-risk group and the
      surveillance and response system should be strengthened to prevent local
      resurgence in Jiangsu.

PMID- 24460983
TI  - Improvement of the cytological diagnostic accuracy of follicular thyroid lesions
      by the use of the Ki-67 proliferative index in addition to cytokeratin-19 and
      HBME-1 immunomarkers: a study of 61 cases of liquid-based FNA cytology with
      histological controls.
AB  - OBJECTIVES: To evaluate HBME-1, cytokeratin-19 (CK-19) and Ki-67 immunomarkers in
      order to increase the diagnostic accuracy of preoperative thyroid fine needle
      aspiration (FNA) cytology. METHODS: Immunocytochemistry against HBME-1, CK-19 and
      Ki-67 was performed on 123 thyroid FNAs processed by liquid-based cytology (LBC).
      Statistical analysis was carried out on 61 cases with histological control and
      sufficient material for one or more of the three markers. The Bethesda System was
      used for cytological diagnosis. RESULTS: Taking into account all the cytological
      categories, with a cut-off of 30% of positive cells, HBME-1 (n = 47) and CK-19 (n
      = 53) showed a sensitivity for malignancy of 66.7% (95% confidence interval, 53.2
      80.1) and 90.5% (82.6-98.4) and a specificity of 90.6% (82.3-99) and 75% (63.3
      86.7), respectively. For Ki-67 (n = 54) with a cut-off of 1% of positive cells,
      the sensitivity was 85.0% (75.5-94.5) and the specificity 70.6% (58.4-82.7). In
      the follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) category (n =
      37), which was the focus of the study, papillary thyroid carcinomas (PTCs) were
      less numerous (four cases, three of which were the follicular variant), the
      positivity of the three immunomarkers combined showed an overall accuracy of 91%
      (21/23). The mean percentage of Ki-67-positive cells was increased in malignant
      lesions, with the exception of follicular variant PTCs: 16% +/- 15.6% in two
      follicular carcinomas, 4.8% +/- 3.2% in 13 classical PTCs, 1% +/- 1.2% in five
      follicular variant PTCs and 0.5% +/- 1.9% in 34 non-malignant lesions.
      CONCLUSIONS: Immunocytochemistry using HBME-1, CK-19 and the Ki-67 proliferative
      index increased the diagnostic accuracy of FNA in the FN/SFN category of the
      Bethesda System, which may help to distinguish lesions in this category with a
      low or high risk of malignancy. Thus, clinical management would be improved.

PMID- 24460984
TI  - Screening for Middle East respiratory syndrome coronavirus infection in hospital
      patients and their healthcare worker and family contacts: a prospective
      descriptive study.
AB  - The Saudi Arabian Ministry of Health implemented a pro-active surveillance
      programme for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). We
      report MERS-CoV data from 5065 Kingdom of Saudi Arabia individuals who were
      screened for MERS-CoV over a 12-month period. From 1 October 2012 to 30 September
      2013, demographic and clinical data were prospectively collected from all
      laboratory forms received at the Saudi Arabian Virology reference laboratory.
      Data were analysed by referral type, age, gender, and MERS-CoV real-time PCR test
      results. Five thousand and 65 individuals were screened for MER-CoV: hospitalized
      patients with suspected MERS-CoV infection (n = 2908, 57.4%), healthcare worker
      (HCW) contacts (n = 1695; 33.5%), and family contacts of laboratory-confirmed
      MERS cases (n = 462; 9.1%). Eleven per cent of persons tested were children (<17
      years of age). There were 108 cases (99 adults and nine children) of MERS-CoV
      infection detected during the 12-month period (108/5065, 2% case detection rate).
      Of 108 cases, 45 were females (six children and 39 adults) and 63 were males
      (three children and 60 adults). Of the 99 adults with MERS-CoV infection, 70 were
      hospitalized patients, 19 were HCW contacts, and ten were family contacts. There
      were no significant increases in MERS-CoV detection rates over the 12-month
      period: 2.6% (19/731) in July 2013, 1.7% (19/1100) in August 2013, and 1.69%
      (21/1238) in September 2013. Male patients had a significantly higher MERS-CoV
      infection rate (63/2318, 2.7%) than females (45/2747, 1.6%) (p 0.013). MERS-CoV
      rates remain at low levels, with no significant increase over time. Pro-active
      surveillance for MERS-CoV in newly diagnosed patients and their contacts will
      continue.

PMID- 24460985
TI  - Efficacy of low-dose intratympanic dexamethasone as a salvage treatment for
      idiopathic sudden sensorineural hearing loss: the Modbury Hospital experience.
AB  - OBJECTIVE: To evaluate the efficacy of low-dose intratympanic dexamethasone
      therapy in patients with idiopathic sudden sensorineural hearing loss whose
      hearing in the affected ear had failed to improve following a course of oral
      steroid therapy. METHODS: A prospective pilot study was undertaken of eight
      patients with idiopathic sudden sensorineural hearing loss whose hearing had
      failed to improve after a course of prednisolone. These patients subsequently
      received 8 mg intratympanic dexamethasone therapy, delivered via a ventilation
      tube on a weekly basis for 1 month. Clinical outcome was assessed weekly with
      pure tone audiography. RESULTS: At the end of the 1-month treatment period, no
      significant hearing improvement was observed on pure tone audiography in any of
      the patients (i.e. improvements were all less than 10 dB). CONCLUSION: The
      response to 8 mg of intratympanic dexamethasone used as a salvage therapy for
      idiopathic sudden sensorineural hearing loss was inadequate. A higher dosage of
      intratympanic dexamethasone might be required to achieve better outcomes.

PMID- 24460987
TI  - But what if the default is defaulting?
AB  - We critically consider the default view of consciousness and decision making, and
      we explore the implications of this view to the authors' argument. We therefore
      call for rigorous collection of data regarding the role of consciousness in
      decisions. We also propose that the section on subliminal effects significantly
      underestimates existing data and succinctly review relevant findings. 

PMID- 24460986
TI  - Identification of a major locus interacting with MC1R and modifying black coat
      color in an F2 Nellore-Angus population.
AB  - BACKGROUND: In cattle, base color is assumed to depend on the enzymatic activity
      specified by the MC1R locus, i.e. the extension locus, with alleles coding for
      black (E(D)), red (e), and wild-type (E+). In most mammals, these alleles are
      presumed to follow the dominance model of E(D) > E+ > e, although exceptions are
      found. In Bos indicus x Bos taurus F2 cattle, some E(D)E+ heterozygotes are
      discordant with the dominance series for MC1R and display various degrees of red
      pigmentation on an otherwise predicted black background. The objective of this
      study was to identify loci that modify black coat color in these individuals.
      RESULTS: Reddening was classified with a subjective scoring system. Interval
      analyses identified chromosome-wide suggestive (P < 0.05) and significant (P <
      0.01) QTL on bovine chromosomes (BTA) 4 and 5, although these were not confirmed
      using single-marker association or Bayesian methods. Evidence of a major locus (F
      = 114.61) that affects reddening was detected between 60 and 73 Mb on BTA 6
      (Btau4.0 build), and at 72 Mb by single-marker association and Bayesian methods.
      The posterior mean of the genetic variance for this region accounted for 43.75%
      of the genetic variation in reddening. This region coincided with a cluster of
      tyrosine kinase receptor genes (PDGFRA, KIT and KDR). Fitting SNP haplotypes for
      a 1 Mb interval that contained all three genes and centered on KIT accounted for
      the majority of the variation attributed to this major locus, which suggests that
      one of these genes or associated regulatory elements, is responsible for the
      majority of variation in degree of reddening. CONCLUSIONS: Recombinants in a 5 Mb
      region surrounding the cluster of tyrosine kinase receptor genes implicated
      PDGFRA as the strongest positional candidate gene. A higher density marker panel
      and functional analyses will be required to validate the role of PDGFRA or other
      regulatory variants and their interaction with MC1R for the modification of black
      coat color in Bos indicus influenced cattle.

PMID- 24460988
TI  - Antimicrobial activity of fluorescent Ag nanoparticles.
AB  - The antimicrobial activity of fluorescent Ag nanoparticles of 1.5 nm (nAg-Fs) is
      demonstrated and compared with the other Ag nanoparticles of different shapes and
      size. The antimicrobial activity was evaluated using Gram-positive
      (Staphylococcus epidermidis NCIM2493 and Bacillus megaterium) and Gram-negative
      bacteria (Pseudomonas aeruginosa ATCC27853 and Escherichia coli) and fungal
      strains (Candida albicans and Aspergillus niger). Insights into the possible
      mechanism were investigated using fluorescence microscope and cytoplasmic
      materials release assay. The fluorescence microscopic measurements show that the
      nAg-Fs are localized at the centre of the cell, and 50% decrease in the
      fluorescence intensity was observed upon 2-h incubation. Maximum cytoplasmic
      release was observed with spherical Ag nanoparticles of 10 nm. Although the nAg-F
      shows minimum cytoplasmic release, it has the highest activity. The microbial
      killing effect of nAg-Fs is actually originates from its intracellular activity.
      The antimicrobial activity of nAg-Fs is significantly higher than the other
      synthesized nanoparticles of different shapes and size. The activity of the
      nanoparticles has been rationalized by considering the shape, size and surface
      structure of the particles. SIGNIFICANCE AND IMPACT OF THE STUDY: This study aims
      to demonstrate the size and shape-dependent antimicrobial activity of Ag
      nanoparticles. It is shown for the first time that the fluorescent Ag
      nanoparticles of 1.5 nm have superior antimicrobial activity with respect to the
      larger particles. The shape and size of the particles actually control their
      activity. The smaller particles can easily penetrate the cell wall and have
      pronounced activity. These findings may be useful in the development of potential
      antimicrobial agents.

PMID- 24460989
TI  - "There is hunger in my community": a qualitative study of food security as a
      cyclical force in sex work in Swaziland.
AB  - BACKGROUND: Swaziland has the highest HIV prevalence in the world - 32% of adults
      are currently living with HIV - and many Swazis are chronically food insecure -
      in 2011 one in four Swazis required food aid from the World Food Programme. In
      southern Africa, food insecurity has been linked to high-risk sexual behaviors,
      difficulty with antiretroviral therapy (ART) adherence, higher rates of mother-to
      child HIV transmission, and more rapid HIV progression. Sex workers in Swaziland
      are a population that is most at risk of HIV. Little is known about the context
      and needs of sex workers in Swaziland who are living with HIV, nor how food
      insecurity may affect these needs. METHODS: In-depth interviews were conducted
      with 20 female sex workers who are living with HIV in Swaziland. Interviews took
      place in four different regions of the country, and were designed to learn about
      context, experiences, and health service needs of Swazi sex workers. RESULTS:
      Hunger was a major and consistent theme in our informants' lives. Women cited
      their own hunger or that of their children as the impetus to begin sex work, and
      as a primary motivation to continue to sell sex. Informants used good nutrition
      and the ability to access "healthy" foods as a strategy to manage their HIV
      infection. Informants discussed difficulty in adhering to ART when faced with the
      prospect of taking pills on an empty stomach. Across interviews, discussions of
      CD4 counts and ART adherence intertwined with discussions of poverty, hunger and
      healthy foods. Some sex workers felt that they had greater trouble accessing food
      through social networks as result of both their HIV status and profession.
      CONCLUSIONS: Informants described a risk cycle of hunger, sex work, and HIV
      infection. The two latter drive an increased need for 'healthy foods' and an
      alienation from social networks that offer material and emotional support against
      hunger. Services and interventions for sex workers which address the pathways
      through which food insecurity generates vulnerability to HIV and social
      marginalization, build sex workers collective efficacy to mobilize, consider
      poverty alleviation, and address social and policy level changes are necessary
      and likely to have the greatest success.

PMID- 24460990
TI  - Silymarin effect on amyloid-beta plaque accumulation and gene expression of APP
      in an Alzheimer's disease rat model.
AB  - BACKGROUND: The deposition of amyloid peptides is associated with Alzheimer's
      disease (AD). These amyloid peptides are derived from the amyloid protein
      precursor (APP). Silymarin, a standardized extract of milk thistle, which is
      currently used in liver diseases, may be effective in the inhibition of amyloid
      formation. However, its effect has not been assessed on APP expression. RESULTS:
      In this study, first, the effect of silymarin was examined on the passive
      avoidance learning in a rat model of AD. This model was induced by the
      intracerebroventricular injection of Abeta peptide (Abeta1-42) in Wistar rats.
      Rats were treated with 70 and 140 mg/kgof the extract, once a day, for 4 weeks.
      Memory function that was evaluated in a shuttle-cage test, showed improvement
      upon administration of this extract. Brain amyloid plaques had also decreased
      upon administration of the extract. Furthermore, APP gene expression was compared
      in treated and untreated groups. The result showed that silymarin was able to
      suppress APP expression. CONCLUSION: Our results are in accordance with the in
      vitro tests concerning the positive antiamyloidogenic property of the main
      component of silymarin, namely silibinin. We suggest that the beneficial effect
      of sylimarin in the AD model is related to its capacity to disaggregate amyloid
      plaques and to suppress APP expression. Considering the limited side effects of
      silymarin, this compound could be of use in AD therapy.

PMID- 24460992
TI  - Population, projections and rural heath.

PMID- 24460991
TI  - Novel method for isolating human melanoblasts from keratinocyte culture.
AB  - The characterization of melanoblasts is important for understanding their in vivo
      development, melanoma formation, and pigment-related disorders. However, no
      methods have been reported for the isolation of melanoblasts from human skin.
      Using a 'calcium-pulse' technique, involving the differentiation of human
      keratinocytes with high calcium and the subsequent spontaneous separation of the
      epidermal sheets, we effectively isolated human melanoblasts (keratinocyte
      adapted melanoblasts, KaMBs) from keratinocyte culture. The KaMBs expressed early
      melanogenesis-related genes, including BRN2, which is a known melanoblast marker.
      Moreover, the KaMBs displayed much higher proliferative and growth capacities
      than the primary melanocytes. Considering that keratinocytes might provide an in
      vivo-like environment for KaMBs during isolation and in vitro culture, the
      'calcium-pulse' technique offers an unprecedented, easy, and efficient method for
      the isolation of human melanoblasts, retaining the original characteristics of
      these cells.

PMID- 24460993
TI  - Mentoring as a retention strategy to sustain the rural and remote health
      workforce.
AB  - OBJECTIVE: To propose a model of mentoring suitable for rural and remote health
      professionals. DESIGN: Given the rural and remote health workforce shortage,
      mentoring is proposed as a workforce retention strategy. Mentoring literature was
      reviewed; aspects of mentoring highlighted in the literature were considered to
      ascertain their suitability for rural and remote health professionals. METHOD: A
      total of 39 mentoring papers were reviewed to outline key factors in mentoring
      rural and remote health professionals. Using this literature, key ways that rural
      and remote practice enhance or are barriers to mentoring were identified. From
      this, a model for mentoring rural and remote health practitioners, students and
      academics was developed. RESULTS: Four models of mentoring were identified: the
      cloning, nurturing, friendship and apprenticeship models. The apprenticeship
      model was identified as suitable for students, the nurturing model as suited to
      new health professionals to rural and remote settings and the friendship model
      for senior practitioners/academics. Factors more likely to enable mentoring in
      rural and remote settings were identified as feelings of obligation by senior
      practitioners, strong relationships between staff, blurred work/social
      boundaries, lack of hierarchy, inter-professional practice and technology. The
      barriers identified included workloads, access to mentors, fee-for-service system
      for some practitioners, conflicts which could jeopardise working and business
      relationships, and feelings of being judged. CONCLUSIONS: A model of mentoring
      for rural and remote health professionals was presented. Given the potential to
      strengthen and increase the rural and remote health workforce, trialling such a
      model is worthwhile and evaluation would identify its impact.

PMID- 24460995
TI  - Sex-specific correlates of adult physical activity in an Australian rural
      community.
AB  - OBJECTIVE: Rural Australians have a higher likelihood of chronic disease and
      lower levels of physical activity than urban Australians. Little is known of the
      factors associated with physical activity among rural-dwelling Australians. This
      study sought to determine the correlates of physical activity among men and women
      of the South Australian Riverland region. DESIGN: Cross-sectional survey.
      SETTING: Regional area. PARTICIPANTS: There are 299 randomly selected 18-65 year
      olds. MAIN OUTCOME MEASURES: Determinations of insufficient and sufficient
      physical activity levels based on public health recommendations. RESULTS: Using
      logistic regression: in men, sufficient physical activity was associated with
      reporting perceived sufficient physical activity for health (odds ratio 3.194
      [1.703-5.989]), and having friends who encouraged physical activity (3.641 [1.450
      9.141]). Men who reported insufficient time (0.350 [0.151-0.812]) and getting
      enough physical activity at their job (0.374 [0.199-0.702]) were less likely to
      be sufficiently active. In women, sufficient physical activity was associated
      with not being employed (2.929 [1.063-8.066]), higher self-efficacy (2.939 [1.118
      7.726]) and having a regular physical activity routine (3.404 [1.829-6.337]).
      Older age (0.960 [0.929-0.995]), poorer self-rated health (0.233 [0.060-0.900])
      and weekend sitting time (0.823 [0.692-0.980]) were negatively associated with
      sufficient physical activity for women. CONCLUSIONS: Factors associated with
      physical activity in this rural adult population differed by sex. Sex-specific
      approaches to promote physical activity might have utility for this population.
      Strategies to enhance social connectedness among men and encourage physical
      activity outside of work can be warranted. Women can require programs to help
      them develop a regular physical activity routine and improve self-efficacy.

PMID- 24460994
TI  - Preparing rural general practitioners and health services for climate change and
      extreme weather.
AB  - OBJECTIVE: To determine the knowledge and recommendations of rural general
      practitioners (GPs) in regard to climate change and the preparedness of rural
      health services for its health impacts. DESIGN: A quantitative descriptive survey
      distributed in paper-based or electronic form. SETTING: Rural Southwest of New
      South Wales. PARTICIPANTS: GPs and GP registrars working in Rural Remote
      Metropolitan Areas (RRMA) 3-7. MAIN OUTCOME MEASURES: Questionnaire responses
      analysed with descriptive statistics and inferential tests. RESULTS: While the
      majority of respondents agreed with statements supporting climate science and the
      impact of climate change on health, between 24% and 34% of respondents were
      unsure or did not agree. Furthermore, between 33% and 44% of GP respondents
      working in RRMA 5-7 were unsure or did not agree that their health service had
      the capacity to provide an initial response to an extreme weather event (P =
      0.01). Strengthening health service acute disaster capacity response was a
      preferred adaptation strategy for improving health service preparedness of 61% of
      participants. A greater proportion of GPs were supportive of their role as
      advocates on general health issues (80%) compared with extreme weather events
      (60%) or climate change and health (63.5%) (P <= 0.01). For professional
      development and education, 71% preferred a locally based workshop or seminar.
      CONCLUSIONS: The study highlights the need to consider closely the views of GPs
      when preparing rural communities for the possible health effects of climate
      change. Findings indicate concern for health service preparedness, particularly
      in smaller rural communities. Further development of disaster response planning
      and communication is needed.

PMID- 24460996
TI  - A public health approach to promoting advance care planning to Aboriginal people
      in regional communities.
AB  - OBJECTIVE: To explore perceptions of Noongar community members towards advance
      care planning (ACP), while developing culturally appropriate information
      resources for use in community and hospital settings. DESIGN: Qualitative
      research methods, combining active health promotion with interviews and group
      discussions for participant feedback. SETTING: Six rural communities across the
      Great Southern region of Western Australia. PARTICIPANTS: Eighteen Noongar
      community members consented to participate in interviews or group discussions.
      INTERVENTIONS: Community members received information about ACP at community
      events or home visits, from an Aboriginal health worker and palliative care
      researcher. MAIN OUTCOME MEASURES: Semi-structured interviews and group
      discussions were thematically analysed using a descriptive, exploratory approach.
      Research team reflections on community events also constituted data. RESULTS: Key
      themes impacting on perceptions of ACP included cultural approaches to dying,
      importance of family and kin, and appropriate communication. Participants were
      satisfied with the information resource and method of community engagement.
      CONCLUSIONS: Culturally appropriate methods of engaging Aboriginal people in ACP
      discussions should include Aboriginal health workers and take a whole of
      community approach to awareness raising.

PMID- 24460997
TI  - Paediatric aeromedical retrievals in the 'Top End' of the Northern Territory.
AB  - OBJECTIVE: The primary objective of this study was to describe the remote
      paediatric aeromedical population of the 'Top End' of the Northern Territory. The
      secondary objective was to identify children requiring high-dependency care by
      the transport team. DESIGN: Retrospective case review. SETTING: Aeromedical
      service in the remote Northern Territory. PARTICIPANTS: All patients under the
      age of 16 years transported over a one-year period between February 2012 and
      February 2013. OUTCOME MEASURES: Age, gestation if newborn, diagnosis at
      referral, requirement for high-dependency care and transport team members.
      RESULTS: Seven hundred eighty-nine children were transported with an average age
      of 4.4 years (range 0 days to 16 years). Nursing staff transferred 646 (82%).
      Respiratory problems (bronchiolitis and pneumonia) were the predominant illness
      type (31%). Other frequent diagnoses were trauma (11%), gastroenteritis (10%),
      cellulitis or abscess (9%) and the sequelae of streptococcal infection (8%).
      Thirty preterm infants including seven below 31 weeks gestation were transferred.
      Twenty-five children required high-dependency care, 15 of these on day 0 of life.
      Twenty-five required respiratory support, seven central venous access, four
      surfactant, two inotropes and one chest tubes. CONCLUSIONS: The majority of
      paediatric aeromedical patients have an infective cause for their illness.
      Respiratory disease is the most common indication for aeromedical transport. The
      majority of patients are transferred by a flight nurse and do not require high
      dependency care. The main risk factor identified for requiring high-dependency
      care during transport is respiratory distress in a newborn infant.

PMID- 24460998
TI  - Evaluation of a rural nurse-led clinic for female sexual dysfunction.
AB  - OBJECTIVE: The objective of this study was to explore changes in the sexual
      function of women who attended a rural nurse-led female sexual dysfunction
      clinic. DESIGN: This exploratory study was designed as a one-group pre-test/post
      test design from a convenience sample of women attending the clinic. SETTING: The
      setting was a women's health centre located in regional Western Australia.
      PARTICIPANTS: One hundred eleven women aged between 18 and 65 years were
      recruited from clinic attendees. MAIN OUTCOME MEASURE(S): The Australian version
      of the validated McCoy Female Sexuality Questionnaire was completed before the
      first appointment (T0), and 1 (T1) and 6 months (T2) after the last appointment.
      RESULTS: Women attending the clinic reported significant increases in sexual
      desire, satisfaction and orgasm quality and achievement at 1 and 6 months after
      their last appointment. There was also a significant increase in satisfaction
      with their main sexual partner at 6 months. CONCLUSIONS: This study confirmed the
      value of an innovative approach to managing female sexual dysfunction in a rural
      area with workforce shortages and limited health services. It is recommended that
      care by a nurse-led multidisciplinary team be used in the management of sexual
      dysfunction. Further research is needed to see if this model of care would be
      effective in other settings.

PMID- 24460999
TI  - Exploring the acceptability of online sexually transmissible infection testing
      for rural young people in Victoria.
AB  - OBJECTIVE: To examine the availability of and previous engagement with health
      services among rural young people and compare barriers and facilitators to using
      face-to-face and online sexual health testing and treatment. DESIGN: Participants
      were recruited for focus groups and were asked to discuss their access to local
      sexual health services (what services they used, when, why and how) and then
      shown a website and asked to provide feedback about online STI testing. SETTING:
      Community sporting clubs in two small country towns in Victoria. PARTICIPANTS:
      Seven focus groups with fifty participants, grouped by gender and age, were
      conducted. MAIN OBJECTIVE MEASURE: Participants views of accessible and
      acceptable services for STI testing. RESULTS: Three main themes emerged from the
      analysis: (i) readiness to seek sexual health services; (ii) barriers and
      facilitators to using the local general practitioner; and (iii) barriers and
      facilitators to online testing, including 'using the mail during online STI
      testing' and 'cost of the online service'. In general, the participants described
      some concerns about accessing sexual health services locally. This was less
      discussion about availability of services and more about privacy, trust,
      reliability and using generalist health care providers for sexual health needs.
      CONCLUSION: Free online testing services address issues of access for rural young
      people. While barriers external to rural sexual health services may remain, free
      online STI testing services are acceptable to these rural young people.

PMID- 24461000
TI  - Bilateral spigelian hernias: diagnosis and treatment in a regional hospital.

PMID- 24461001
TI  - New dawn for rural allied health.

PMID- 24461002
TI  - Ceppellini Lecture 2012: collateral damage from HLA mismatching in kidney
      transplantation.
AB  - Inclusion of human leukocyte antigen (HLA) matching in donor kidney allocation
      schemes has been based solely on its association with graft survival. Other long
      term effects associated with HLA incompatibility are largely unexplored. Data
      from deceased donor kidney transplants reported to the Collaborative Transplant
      Study have been analyzed to assess the relation between HLA mismatching and
      clinical events to 3 years post-transplant, and an overview of these analyses is
      presented. A significant correlation was observed between the number of
      mismatches and the need for anti-rejection therapy during the first year post
      transplant, which was maintained for HLA-DR and HLA-A + B mismatching separately
      and at years 2 and 3 post-transplant. The number of HLA-DR mismatches and the
      number of HLA-A + B mismatches as well as rejection treatment showed significant
      associations with the dose of maintenance steroids. The cumulative incidences of
      death with a functioning graft from infection or cardiovascular causes, but not
      from cancer, were also significantly associated with HLA mismatching. The number
      of HLA-DR mismatches showed a significant association with the incidence of non
      Hodgkin lymphoma and hip fractures. These findings show that the adverse
      consequences of HLA mismatching on kidney transplants extend beyond an effect on
      graft survival, and include an increased risk of death with a functioning graft,
      non-Hodgkin lymphoma and hip fracture. 

PMID- 24461003
TI  - Evaluation of peptide selection approaches for epitope-based vaccine design.
AB  - A major challenge in epitope-based vaccine (EV) design stems from the vast
      genomic variation of pathogens and the diversity of the host cellular immune
      system. Several computational approaches have been published to assist the
      selection of potential T cell epitopes for EV design. So far, no thorough
      comparison between the current methods has been realized. Using human
      immunodeficiency virus as test case, different EV selection algorithms were
      evaluated with respect to their ability to select small peptides sets with broad
      coverage of allelic and pathogenic diversity. The methods were compared in terms
      of in silico measurements simulating important vaccine properties like the
      ability of inducing protection against a multivariant pathogen in a population;
      the predicted immunogenicity; pathogen, allele, and population coverage; as well
      as the conservation of selected epitopes. Additionally, we evaluate the use of
      human leukocyte antigen (HLA) supertypes with regards to their applicability for
      population-spanning vaccine design. The results showed that in terms of induced
      protection methods that simultaneously aim to optimize pathogen and HLA coverage
      significantly outperform methods focusing on pathogen coverage alone. Moreover,
      supertype-based approaches for coverage of HLA diversity were showed to yield
      only satisfying results in populations in which the supertype representatives are
      prevalent. 

PMID- 24461004
TI  - HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in Saudis using
      next generation sequencing technique.
AB  - Next generation sequencing (NGS) is a promising technique that can reveal the
      entire gene sequences and to the highest possible resolution without any phase
      ambiguities. We have used this technique to investigate the frequencies of HLA-A,
      -B, -C, -DRB1 and -DQB1 in a Saudi cohort of healthy individuals. We used NGS
      using the 454 genome sequence (GS) FLX System and Conexio assign atf 454 software
      to human leukocyte antigen (HLA) genotype eight class I and class II loci. A
      total of 158 healthy Saudi adults were analyzed. The most frequently observed
      allele for HLA-A was HLA-A*02:01:01:01 (13.6%); for HLA-B, HLA-B*50:01:01
      (15.8%); for HLA-C, HLA-C*06:02:01:01 (18.7%); for HLA-DRB1, HLA-DRB1*07:01:01:01
      (26.6%); and for HLA-DQB1, HLA-DQB1*02:01:01 (20.3%). The most common four loci
      haplotypes in the Saudi population were HLA-A*24:02:01:01-B*08:01:01
      C*07:02:01:01-DRB1*03:01:01:01 and HLA-A*23:01:01-B*50:01:01-C*06:02:01:01
      DRB1*07:01:01:01.. We have used a highly informative technique for HLA typing of
      a Saudi healthy cohort to establish allele and haplotype frequencies. These
      results should prove useful for population studies, disease associations and
      future planning of the unrelated bone marrow donor registry.

PMID- 24461005
TI  - Microarrays for high-throughput genotyping of MICA alleles using allele-specific
      primer extension.
AB  - The role of major histocompatibility complex (MHC) class I chain-related gene A
      (MICA), a ligand of NKG2D, has been defined in human diseases by its allele
      associations with various autoimmune diseases, hematopoietic stem cell
      transplantation (HSCT) and cancer. This study describes a practical system to
      develop MICA genotyping by allele-specific primer extension (ASPE) on
      microarrays. From the results of 20 control primers, strict and reliable cut-off
      values of more than 30,000 mean fluorescence intensity (MFI) as positive and less
      than 3000 MFI as negative, were applied to select high-quality specific extension
      primers. Among 55 allele-specific primers, 44 primers could be initially selected
      as optimal primer. Through adjusting the length, six primers were improved. The
      other failed five primers were corrected by refractory modification. MICA
      genotypes by ASPE on microarrays showed the same results as those by nucleotide
      sequencing. On the basis of these results, ASPE on microarrays may provide high
      throughput genotyping for MICA alleles for population studies, disease-gene
      associations and HSCT. 

PMID- 24461006
TI  - Assessment of the purity of isolated cell populations for lineage-specific
      chimerism monitoring post haematopoietic stem cell transplantation.
AB  - Following haematopoietic stem cell transplantation, monitoring the proportion of
      donor and recipient haematopoiesis in the patient (chimerism) is an influential
      tool in directing further treatment choices. Short tandem repeat (STR) analysis
      is a method of chimerism monitoring using DNA isolated from peripheral blood,
      bone marrow or specific isolated cell lineages such as CD3+ T cells. For lineage
      specific STR analysis on cell populations isolated from peripheral blood, a
      qualitative estimation of the purity of each isolated population is essential for
      the correct interpretation of the test data. We describe a rapid, inexpensive
      method for the determination of purity using a simple flow cytometry method. The
      method described for assessing the purity of sorted CD3+ cells can be applied to
      any cell population isolated using the same technology. Data obtained were
      comparable to results from a commercial polymerase chain reaction (PCR)-based
      method for the assessment of purity (Non-T Genomic Detection Kit, Accumol,
      Calgary, AB, Canada) (P = 0.59). Of the 303 samples tested by flow cytometry, 290
      (95.7%) exceeded 90% purity, and 215 (70.95%) were over 99% pure. There were some
      outlying samples, showing diversity between samples and the unpredictability of
      purity of isolated cell populations. This flow cytometry method can be easily
      assimilated into routine testing protocols, allowing purity assessment in
      multiple-sorted cell populations for lineage-specific chimerism monitoring using
      a single secondary antibody and giving results comparable to a PCR-based method.
      As purity of isolated cell lineages is affected by time after venepuncture and
      storage temperature, assessment of each sample is recommended to give a reliable
      indication of sample quality and confidence in the interpretation of the results.

PMID- 24461007
TI  - Identification of a new allele polymorphism (HLA-B*40:79) and correlation with
      the HLA-B40 (B60 and B61) antigens.
AB  - Full gene sequence of the HLA-B*40:79 allele; gene polymorphism defines HLA-B60
      and B61 lineages. 

PMID- 24461008
TI  - Atrial fibrillation alters the microRNA expression profiles of the left atria of
      patients with mitral stenosis.
AB  - BACKGROUND: Structural changes of the left and right atria associated with atrial
      fibrillation (AF) in mitral stenosis (MS) patients are well known, and
      alterations in microRNA (miRNA) expression profiles of the right atria have also
      been investigated. However, miRNA changes in the left atria still require
      delineation. This study evaluated alterations in miRNA expression profiles of
      left atrial tissues from MS patients with AF relative to those with normal sinus
      rhythm (NSR). METHODS: Sample tissues from left atrial appendages were obtained
      from 12 MS patients (6 with AF) during mitral valve replacement surgery. From
      these tissues, miRNA expression profiles were created and analyzed using a human
      miRNA microarray. Results were validated via reverse-transcription and
      quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted
      and their functions and potential pathways analyzed via the miRFocus database.
      RESULTS: The expression levels of 22 miRNAs differed between the AF and NSR
      groups. Relative to NSR patients, in those with AF the expression levels of 45%
      (10/22) of these miRNAs were significantly higher, while those of the balance
      (55%, 12/22) were significantly lower. Potential miRNA targets and molecular
      pathways were identified. CONCLUSIONS: AF alters the miRNA expression profiles of
      the left atria of MS patients. These findings may be useful for the biological
      understanding of AF in MS patients.

PMID- 24461009
TI  - Quantitative analysis of ezrin turnover dynamics in the actin cortex.
AB  - Proteins of the ERM family (ezrin, moesin, radixin) play a fundamental role in
      tethering the membrane to the cellular actin cortex as well as regulating
      cortical organization and mechanics. Overexpression of dominant inactive forms of
      ezrin leads to fragilization of the membrane-cortex link and depletion of moesin
      results in softer cortices that disrupt spindle orientation during cytokinesis.
      Therefore, the kinetics of association of ERM proteins with the cortex likely
      influence the timescale of cortical signaling events and the dynamics of membrane
      interfacing to the cortex. However, little is known about ERM protein turnover at
      the membrane-cortex interface. Here, we examined cortical ezrin dynamics using
      fluorescence recovery after photobleaching experiments and single-molecule
      imaging. Using multiexponential fitting of fluorescence recovery curves, we
      showed that ezrin turnover resulted from three molecular mechanisms acting on
      very different timescales. The fastest turnover process was due to
      association/dissociation from the F-actin cortex, suggesting that ezrin acts as a
      link that leads to low friction between the membrane and the cortex. The second
      turnover process resulted from association/dissociation of ezrin from the
      membrane and the slowest turnover process resulted from the slow diffusion of
      ezrin in the plane of the membrane. In summary, ezrin-mediated membrane-cortex
      tethering resulted from long-lived interactions with the membrane via the FERM
      domain coupled with shorter-lived interactions with the cortex. The slow
      diffusion of membranous ezrin and its interaction partners relative to the cortex
      signified that signals emanating from membrane-associated ezrin may locally act
      to modulate cortical organization and contractility. 

PMID- 24461010
TI  - Differentiation of Col I and Col III isoforms in stromal models of ovarian cancer
      by analysis of second harmonic generation polarization and emission
      directionality.
AB  - A profound remodeling of the extracellular matrix occurs in many epithelial
      cancers. In ovarian cancer, the minor collagen isoform of Col III becomes
      upregulated in invasive disease. Here we use second harmonic generation (SHG)
      imaging microscopy to probe structural differences in fibrillar models of the
      ovarian stroma comprised of mixtures of Col I and III. The SHG intensity and
      forward-backward ratios decrease with increasing Col III content, consistent with
      decreased phasematching due to more randomized structures. We further probe the
      net collagen alpha-helix pitch angle within the gel mixtures using what is
      believed to be a new pixel-based polarization-resolved approach that combines and
      extends previous analyses. The extracted pitch angles are consistent with those
      of peptide models and the method has sufficient sensitivity to differentiate Col
      I from the Col I/Col III mixtures. We further developed the pixel-based approach
      to extract the SHG signal polarization anisotropy from the same polarization
      resolved image matrix. Using this approach, we found that increased Col III
      results in decreased alignment of the dipole moments within the focal volume.
      Collectively, the SHG measurements and analysis all indicate that incorporation
      of Col III results in decreased organization across several levels of collagen
      organization. Furthermore, the findings suggest that the collagen isoforms
      comingle within the same fibrils, in good agreement with ultrastructural data.
      The pixel-based polarization analyses (both excitation and emission) afford
      determination of structural properties without the previous requirement of having
      well-aligned fibers, and the approaches should be generally applicable in tissue.

PMID- 24461011
TI  - Microvascular endothelial cells migrate upstream and align against the shear
      stress field created by impinging flow.
AB  - At present, little is known about how endothelial cells respond to spatial
      variations in fluid shear stress such as those that occur locally during
      embryonic development, at heart valve leaflets, and at sites of aneurysm
      formation. We built an impinging flow device that exposes endothelial cells to
      gradients of shear stress. Using this device, we investigated the response of
      microvascular endothelial cells to shear-stress gradients that ranged from 0 to a
      peak shear stress of 9-210 dyn/cm(2). We observe that at high confluency, these
      cells migrate against the direction of fluid flow and concentrate in the region
      of maximum wall shear stress, whereas low-density microvascular endothelial cells
      that lack cell-cell contacts migrate in the flow direction. In addition, the
      cells align parallel to the flow at low wall shear stresses but orient
      perpendicularly to the flow direction above a critical threshold in local wall
      shear stress. Our observations suggest that endothelial cells are exquisitely
      sensitive to both magnitude and spatial gradients in wall shear stress. The
      impinging flow device provides a, to our knowledge, novel means to study
      endothelial cell migration and polarization in response to gradients in physical
      forces such as wall shear stress. 

PMID- 24461012
TI  - Dynamics of protein-protein interactions at the MscL periplasmic-lipid interface.
AB  - MscL, the highly conserved bacterial mechanosensitive channel of large
      conductance, is one of the best studied mechanosensors. It is a homopentameric
      channel that serves as a biological emergency release valve that prevents cell
      lysis from acute osmotic stress. We previously showed that the periplasmic region
      of the protein, particularly a single residue located at the TM1/periplasmic loop
      interface, F47 of Staphylococcus aureus and I49 of Escherichia coli MscL, plays a
      major role in both the open dwell time and mechanosensitivity of the channel.
      Here, we introduced cysteine mutations at these sites and found they formed
      disulfide bridges that decreased the channel open dwell time. By scanning a
      likely interacting domain, we also found that these sites could be disulfide
      trapped by addition of cysteine mutations in other locations within the
      periplasmic loop of MscL, and this also led to rapid channel kinetics. Together,
      the data suggest structural rearrangements and protein-protein interactions that
      occur within this region upon normal gating, and further suggest that locking
      portions of the channel into a transition state decreases the stability of the
      open state. 

PMID- 24461013
TI  - Quantitation of the calcium and membrane binding properties of the C2 domains of
      dysferlin.
AB  - Dysferlin is a large membrane protein involved in calcium-triggered resealing of
      the sarcolemma after injury. Although it is generally accepted that dysferlin is
      Ca(2+) sensitive, the Ca(2+) binding properties of dysferlin have not been
      characterized. In this study, we report an analysis of the Ca(2+) and membrane
      binding properties of all seven C2 domains of dysferlin as well as a multi-C2
      domain construct. Isothermal titration calorimetry measurements indicate that all
      seven dysferlin C2 domains interact with Ca(2+) with a wide range of binding
      affinities. The C2A and C2C domains were determined to be the most sensitive,
      with Kd values in the tens of micromolar, whereas the C2D domain was least
      sensitive, with a near millimolar Kd value. Mutagenesis of C2A demonstrates the
      requirement for negatively charged residues in the loop regions for divalent ion
      binding. Furthermore, dysferlin displayed significantly lower binding affinity
      for the divalent cations magnesium and strontium. Measurement of a multidomain
      construct indicates that the solution binding affinity does not change when C2
      domains are linked. Finally, sedimentation assays suggest all seven C2 domains
      bind lipid membranes, and that Ca(2+) enhances but is not required for
      interaction. This report reveals for the first time, to our knowledge, that all
      dysferlin domains bind Ca(2+) albeit with varying affinity and stoichiometry. 

PMID- 24461014
TI  - Active-site structure of the thermophilic Foc-subunit ring in membranes
      elucidated by solid-state NMR.
AB  - FoF1-ATP synthase uses the electrochemical potential across membranes or ATP
      hydrolysis to rotate the Foc-subunit ring. To elucidate the underlying mechanism,
      we carried out a structural analysis focused on the active site of the
      thermophilic c-subunit (TFoc) ring in membranes with a solid-state NMR method
      developed for this purpose. We used stereo-array isotope labeling (SAIL) with a
      cell-free system to highlight the target. TFoc oligomers were purified using a
      virtual ring His tag. The membrane-reconstituted TFoc oligomer was confirmed to
      be a ring indistinguishable from that expressed in E. coli on the basis of the
      H(+)-translocation activity and high-speed atomic force microscopic images. For
      the analysis of the active site, 2D (13)C-(13)C correlation spectra of TFoc rings
      labeled with SAIL-Glu and -Asn were recorded. Complete signal assignment could be
      performed with the aid of the C(alpha)i+1-C(alpha)i correlation spectrum of
      specifically (13)C,(15)N-labeled TFoc rings. The C(delta) chemical shift of Glu
      56, which is essential for H(+) translocation, and related crosspeaks revealed
      that its carboxyl group is protonated in the membrane, forming the H(+)-locked
      conformation with Asn-23. The chemical shift of Asp-61 C(gamma) of the E. coli c
      ring indicated an involvement of a water molecule in the H(+) locking, in
      contrast to the involvement of Asn-23 in the TFoc ring, suggesting two different
      means of proton storage in the c rings. 

PMID- 24461015
TI  - Enhanced tethered-particle motion analysis reveals viscous effects.
AB  - Tethered-particle motion experiments do not require expensive or technically
      complex hardware, and increasing numbers of researchers are adopting this
      methodology to investigate the topological effects of agents that act on the
      tethering polymer or the characteristics of the polymer itself. These
      investigations depend on accurate measurement and interpretation of changes in
      the effective length of the tethering polymer (often DNA). However, the bead
      size, tether length, and buffer affect the confined diffusion of the bead in this
      experimental system. To evaluate the effects of these factors, improved
      measurements to calibrate the two-dimensional range of motion (excursion) versus
      DNA length were carried out. Microspheres of 160 or 240 nm in radius were
      tethered by DNA molecules ranging from 225 to 3477 basepairs in length in aqueous
      buffers containing 100 mM potassium glutamate and 8 mM MgCl2 or 10 mM Tris-HCl
      and 200 mM KCl, with or without 0.5% Tween added to the buffer, and the motion
      was recorded. Different buffers altered the excursion of beads on identical DNA
      tethers. Buffer with only 10 mM NaCl and >5 mM magnesium greatly reduced
      excursion. Glycerol added to increase viscosity slowed confined diffusion of the
      tethered beads but did not change excursion. The confined-diffusion coefficients
      for all tethered beads were smaller than those expected for freely diffusing
      beads and decreased for shorter tethers. Tethered-particle motion is a sensitive
      framework for diffusion experiments in which small beads on long leashes most
      closely resemble freely diffusing, untethered beads. 

PMID- 24461016
TI  - Thermodynamic characterization of the unfolding of the prion protein.
AB  - The prion protein appears to be unusually susceptible to conformational change,
      and unlike nearly all other proteins, it can easily be made to convert to
      alternative misfolded conformations. To understand the basis of this structural
      plasticity, a detailed thermodynamic characterization of two variants of the
      mouse prion protein (moPrP), the full-length moPrP (23-231) and the structured C
      terminal domain, moPrP (121-231), has been carried out. All thermodynamic
      parameters governing unfolding, including the changes in enthalpy, entropy, free
      energy, and heat capacity, were found to be identical for the two protein
      variants. The N-terminal domain remains unstructured and does not interact with
      the C-terminal domain in the full-length protein at pH 4. Moreover, the enthalpy
      and entropy of unfolding of moPrP (121-231) are similar in magnitude to values
      reported for other proteins of similar size. However, the protein has an
      unusually high native-state heat capacity, and consequently, the change in heat
      capacity upon unfolding is much lower than that expected for a protein of similar
      size. It appears, therefore, that the native state of the prion protein undergoes
      substantial fluctuations in enthalpy and hence, in structure. 

PMID- 24461017
TI  - Atomic level rendering of DNA-drug encounter.
AB  - Computer simulations have been demonstrated to be important for unraveling atomic
      mechanisms in biological systems. In this study, we show how combining unbiased
      molecular dynamic simulations with appropriate analysis tools can successfully
      describe metal-based drug interactions with DNA. To elucidate the noncovalent
      affinity of cisplatin's family to DNA, we performed extensive all-atom molecular
      dynamics simulations (3.7 MUs total simulation length). The results show that the
      parent drug, cisplatin, has less affinity to form noncovalent adducts in the
      major groove than its aquo complexes. Furthermore, the relative position in which
      the drugs enter the major groove is dependent on the compound's net charge. Based
      on the simulations, we estimated noncovalent binding free energies through the
      use of Markov state models. In addition, and to overcome the lack of experimental
      information, we employed two additional methods: Molecular Mechanics Poisson
      Boltzmann Surface Area (MMPB-SA) and steered molecular dynamics with the
      Jarzynski estimator, with an overall good agreement between the three methods.
      All complexes show interaction energies below 3 kcal/mol with DNA but the charged
      hydrolysis products have slightly more favorable binding free energies than the
      parent drug. Moreover, this study sets the precedent for future unbiased DNA
      ligand simulations of more complex binders. 

PMID- 24461018
TI  - Reconstruction and identification of DNA sequence landscapes from unzipping
      experiments at equilibrium.
AB  - Two methods for reconstructing the free-energy landscape of a DNA molecule from
      the knowledge of the equilibrium unzipping force versus extension signal are
      introduced: a simple and fast procedure, based on a parametric representation of
      the experimental force signal, and a maximum-likelihood inference of coarse
      grained free-energy parameters. In addition, we propose a force alignment
      procedure to correct for the drift in the experimental measure of the opening
      position, a major source of error. For unzipping data obtained by Huguet et al.,
      the reconstructed basepair (bp) free energies agree with the running average of
      the true free energies on a 20-50 bp scale, depending on the region in the
      sequence. Features of the landscape at a smaller scale (5-10 bp) could be
      recovered in favorable regions at the beginning of the molecule. Based on the
      analysis of synthetic data corresponding to the 16S rDNA gene of bacteria, we
      show that our approach could be used to identify specific DNA sequences among
      thousands of homologous sequences in a database. 

PMID- 24461019
TI  - Elucidating the aggregation number of dopamine-induced alpha-synuclein oligomeric
      assemblies.
AB  - Conventional methods to determine the aggregation number, that is, the number of
      monomers per oligomer, struggle to yield reliable results for large protein
      aggregates, such as amyloid oligomers. We have previously demonstrated the use of
      a combination of single-molecule photobleaching and substoichiometric fluorescent
      labeling to determine the aggregation number of oligomers of human alpha
      synuclein, implicated in Parkinson's disease. We show here that this approach is
      capable of accurately resolving mixtures of multiple distinct molecular species
      present in the same sample of dopamine-induced alpha-synuclein oligomers, and
      that we can determine the respective aggregation numbers of each species from a
      single histogram of bleaching steps. We found two distinct species with
      aggregation numbers of 15-19 monomers and 34-38 monomers. These results show that
      this single-molecule approach allows for the systematic study of the aggregation
      numbers of complex supramolecular assemblies formed under different aggregation
      conditions. 

PMID- 24461020
TI  - Interconversion between parallel and antiparallel conformations of a 4H RNA
      junction in domain 3 of foot-and-mouth disease virus IRES captured by dynamics
      simulations.
AB  - RNA junctions are common secondary structural elements present in a wide range of
      RNA species. They play crucial roles in directing the overall folding of RNA
      molecules as well as in a variety of biological functions. In particular, there
      has been great interest in the dynamics of RNA junctions, including
      conformational pathways of fully base-paired 4-way (4H) RNA junctions. In such
      constructs, all nucleotides participate in one of the four double-stranded stem
      regions, with no connecting loops. Dynamical aspects of these 4H RNAs are
      interesting because frequent interchanges between parallel and antiparallel
      conformations are thought to occur without binding of other factors. Gel
      electrophoresis and single-molecule fluorescence resonance energy transfer
      experiments have suggested two possible pathways: one involves a helical
      rearrangement via disruption of coaxial stacking, and the other occurs by a
      rotation between the helical axes of coaxially stacked conformers. Employing
      molecular dynamics simulations, we explore this conformational variability in a
      4H junction derived from domain 3 of the foot-and-mouth disease virus internal
      ribosome entry site (IRES); this junction contains highly conserved motifs for
      RNA-RNA and RNA-protein interactions, important for IRES activity. Our
      simulations capture transitions of the 4H junction between parallel and
      antiparallel conformations. The interconversion is virtually barrier-free and
      occurs via a rotation between the axes of coaxially stacked helices with a
      transient perpendicular intermediate. We characterize this transition, with
      various interhelical orientations, by pseudodihedral angle and interhelical
      distance measures. The high flexibility of the junction, as also demonstrated
      experimentally, is suitable for IRES activity. Because foot-and-mouth disease
      virus IRES structure depends on long-range interactions involving domain 3, the
      perpendicular intermediate, which maintains coaxial stacking of helices and
      thereby consensus primary and secondary structure information, may be beneficial
      for guiding the overall organization of the RNA system in domain 3. 

PMID- 24461021
TI  - Coherent x-ray imaging of collagen fibril distributions within intact tendons.
AB  - The characterization of the structure of highly hierarchical biosamples such as
      collagen-based tissues at the scale of tens of nanometers is essential to
      correlate the tissue structure with its growth processes. Coherent x-ray Bragg
      ptychography is an innovative imaging technique that gives high resolution images
      of the ordered parts of such samples. Herein, we report how we used this method
      to image the collagen fibrillar ultrastructure of intact rat tail tendons. The
      images show ordered fibrils extending over 10-20 MUm in length, with a
      quantifiable D-banding spacing variation of 0.2%. Occasional defects in the
      fibrils distribution have also been observed, likely indicating fibrillar fusion
      events. 

PMID- 24461022
TI  - Delays induce novel stochastic effects in negative feedback gene circuits.
AB  - Stochastic models of reaction networks are widely used to depict gene expression
      dynamics. However, stochastic does not necessarily imply accurate, as subtle
      assumptions can yield erroneous results, masking key discrete effects. For
      instance, transcription and translation are not instantaneous processes-explicit
      delays separate their initiation from the appearance of their functional
      products. However, delays are often ignored in stochastic, single-gene expression
      models. By consequence, effects such as delay-induced stochastic oscillations at
      the single-cell level have remained relatively unexplored. Here, we present a
      systematic study of periodicity and multimodality in a simple gene circuit with
      negative feedback, analyzing the influence of negative feedback strength and
      transcriptional/translational delays on expression dynamics. We demonstrate that
      an oscillatory regime emerges through a Hopf bifurcation in both deterministic
      and stochastic frameworks. Of importance, a shift in the stochastic Hopf
      bifurcation evidences inaccuracies of the deterministic bifurcation analysis.
      Furthermore, noise fluctuations within stochastic oscillations decrease alongside
      increasing values of transcriptional delays and within a specific range of
      negative feedback strengths, whereas a strong feedback is associated with
      oscillations triggered by bursts. Finally, we demonstrate that explicitly
      accounting for delays increases the number of accessible states in the multimodal
      regime, and also introduces features typical of excitable systems. 

PMID- 24461023
TI  - Promoter-mediated transcriptional dynamics.
AB  - Genes in eukaryotic cells are typically regulated by complex promoters containing
      multiple binding sites for a variety of transcription factors, but how promoter
      dynamics affect transcriptional dynamics has remained poorly understood. In this
      study, we analyze gene models at the transcriptional regulation level, which
      incorporate the complexity of promoter structure (PS) defined as transcriptional
      exits (i.e., ON states of the promoter) and the transition pattern (described by
      a matrix consisting of transition rates among promoter activity states). We show
      that multiple exits of transcription are the essential origin of generating
      multimodal distributions of mRNA, but promoters with the same transition pattern
      can lead to multimodality of different modes, depending on the regulation of
      transcriptional factors. In turn, for similar mRNA distributions in the models,
      the mean ON or OFF time distributions may exhibit different characteristics, thus
      providing the supplemental information on PS. In addition, we demonstrate that
      the transcriptional noise can be characterized by a nonlinear function of mean ON
      and OFF times. These results not only reveal essential characteristics of
      promoter-mediated transcriptional dynamics but also provide signatures useful for
      inferring PS based on characteristics of transcriptional outputs. 

PMID- 24461024
TI  - Comment on the letter by A. Ben-Shaul: "entropy, energy, and bending of DNA in
      viral capsids".
AB  - The conformational entropic penalty associated with packaging double-stranded DNA
      into viral capsids remains an issue of contention. So far, models based on a
      continuum approximation for DNA have either left the question unexamined, or they
      have assumed that the entropic penalty is negligible, following an early analysis
      by Riemer and Bloomfield. In contrast, molecular-dynamics (MD) simulations using
      bead-and-spring models consistently show a large penalty. A recent letter from
      Ben-Shaul attempts to reconcile the differences. While the letter makes some
      valid points, the issue of how to include conformational entropy in the continuum
      models remains unresolved. In this Comment, I show that the free energy
      decomposition from continuum models could be brought into line with the
      decomposition from the MD simulations with two adjustments. First, the entropy
      from Flory-Huggins theory should be replaced by the estimate of the entropic
      penalty given in Ben-Shaul's letter, which corresponds closely to that from the
      MD simulations. Second, the DNA-DNA repulsions are well described by the
      empirical relationship given by the Cal Tech group, but the strength of these
      should be reduced by about half, using parameters based on the Rau-Parsegian
      experiments, rather than treating them as "fitting parameters (tuned) to fit the
      data from (single molecule pulling) experiments." 

PMID- 24461025
TI  - Reply to the comment by S. Harvey on "entropy, energy, and bending of DNA in
      viral capsids".
AB  - The comment by Stephen Harvey in this issue of the Biophysical Journal concludes
      with two statements regarding my recent letter about DNA packaging into viral
      capsids. Harvey agrees with my interpretation of the origin of the large
      confinement entropy predicted by the molecular-dynamics simulations of his group,
      and its sensitive dependence on the molecular parameters of their wormlike chain
      model of double-stranded DNA. On the other hand, he doubts my assertion that the
      confinement entropy is already included in the interstrand repulsion free energy
      derived from osmotic stress measurements, which constitutes the major
      contribution to the packaging free energy used in recent continuum theories of
      this process. Harvey suggests instead that the confinement entropy should be
      added to this free energy as a separate term (using, for instance, the method
      described in my letter). I will argue that this addition is redundant, and, in a
      brief discussion of continuum theories, will also discuss his comments as relates
      to the work of other researchers. 

PMID- 24461027
TI  - Discriminating between anomalous diffusion and transient behavior in
      microheterogeneous environments.
AB  - Diffusion in macrohomogeneous and microheterogeneous media can be described as
      effective free diffusion only at sufficiently long times. At intermediate times,
      the mean-square displacement of a diffusing object shows a transient behavior
      that can be misinterpreted as anomalous subdiffusion. We discuss how to
      discriminate between the two. 

PMID- 24461026
TI  - Quantifying interactions of a membrane protein embedded in a lipid nanodisc using
      fluorescence correlation spectroscopy.
AB  - Using fluorescence correlation spectroscopy, we measured a dissociation constant
      of 20 nM between EGFP-labeled LcrV from Yersinia pestis and its cognate membrane
      bound protein YopB inserted into a lipid nanodisc. The combination of
      fluorescence correlation spectroscopy and nanodisc technologies provides a
      powerful approach to accurately measure binding constants of interactions between
      membrane bound and soluble proteins in solution. Straightforward sample
      preparation, acquisition, and analysis procedures make this combined technology
      attractive for accurately measuring binding kinetics for this important class of
      protein-protein interactions. 

PMID- 24461028
TI  - Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and
      coronary angiography combined with fractional flow reserve for the diagnosis of
      coronary artery disease.
AB  - BACKGROUND: According to recent guidelines, patients with coronary artery disease
      (CAD) should undergo revascularization if significant myocardial ischemia is
      present. Both, cardiovascular magnetic resonance (CMR) and fractional flow
      reserve (FFR) allow for a reliable ischemia assessment and in combination with
      anatomical information provided by invasive coronary angiography (CXA), such a
      work-up sets the basis for a decision to revascularize or not. The cost
      effectiveness ratio of these two strategies is compared. METHODS: Strategy 1) CMR
      to assess ischemia followed by CXA in ischemia-positive patients (CMR + CXA),
      Strategy 2) CXA followed by FFR in angiographically positive stenoses (CXA +
      FFR). The costs, evaluated from the third party payer perspective in Switzerland,
      Germany, the United Kingdom (UK), and the United States (US), included public
      prices of the different outpatient procedures and costs induced by procedural
      complications and by diagnostic errors. The effectiveness criterion was the
      correct identification of hemodynamically significant coronary lesion(s) (=
      significant CAD) complemented by full anatomical information. Test performances
      were derived from the published literature. Cost-effectiveness ratios for both
      strategies were compared for hypothetical cohorts with different pretest
      likelihood of significant CAD. RESULTS: CMR + CXA and CXA + FFR were equally cost
      effective at a pretest likelihood of CAD of 62% in Switzerland, 65% in Germany,
      83% in the UK, and 82% in the US with costs of CHF 5'794, ? 1'517, L 2'680, and $
      2'179 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed
      lower costs per patient correctly diagnosed than CXA + FFR. CONCLUSIONS: The CMR
      + CXA strategy is more cost-effective than CXA + FFR below a CAD prevalence of
      62%, 65%, 83%, and 82% for the Swiss, the German, the UK, and the US health care
      systems, respectively. These findings may help to optimize resource utilization
      in the diagnosis of CAD.

PMID- 24461029
TI  - Comparative absorption of curcumin formulations.
AB  - BACKGROUND: The potential health benefits of curcumin are limited by its poor
      solubility, low absorption from the gut, rapid metabolism and rapid systemic
      elimination. The purpose of this study was the comparative measurement of the
      increases in levels of curcuminoids (curcumin, demethoxycurcumin,
      bisdemethoxycurcumin) and the metabolite tetrahydrocurcumin after oral
      administration of three different curcumin formulations in comparison to
      unformulated standard. METHODS: The relative absorption of a curcumin phytosome
      formulation (CP), a formulation with volatile oils of turmeric rhizome (CTR) and
      a formulation of curcumin with a combination of hydrophilic carrier, cellulosic
      derivatives and natural antioxidants (CHC) in comparison to a standardized
      curcumin mixture (CS) was investigated in a randomized, double-blind, crossover
      human study in healthy volunteers. Samples were analyzed by HPLC-MS/MS. RESULTS:
      Total curcuminoids appearance in the blood was 1.3-fold higher for CTR and 7.9
      fold higher for CP in comparison to unformulated CS. CHC showed a 45.9-fold
      higher absorption over CS and significantly improved absorption over CP (5.8
      fold) and CTR (34.9-fold, all p < 0.001). CONCLUSION: A formulation of curcumin
      with a combination of hydrophilic carrier, cellulosic derivatives and natural
      antioxidants significantly increases curcuminoid appearance in the blood in
      comparison to unformulated standard curcumin CS, CTR and CP.

PMID- 24461030
TI  - Patient loyalty in a mature IDS market: is population health management worth it?
AB  - OBJECTIVE: To understand patient loyalty to providers over time, informing
      effective population health management. STUDY SETTING: Patient care-seeking
      patterns over a 6-year timeframe in Minnesota, where care systems have a
      significant portion of their revenue generated by shared-saving contracts with
      public and private payers. STUDY DESIGN: Weibull duration and probit models were
      used to examine patterns of patient attribution to a care system and the
      continuity of patient affiliation with a care system. Clustering of errors within
      family unit was used to account for within-family correlation in unobserved
      characteristics that affect patient loyalty. DATA COLLECTION: The payer provided
      data from health plan administrative files, matched to U.S. Census-based
      characteristics of the patient's neighborhood. Patients were retrospectively
      attributed to health care systems based on patterns of primary care. PRINCIPAL
      FINDINGS: I find significant patient loyalty, with past loyalty a very strong
      predictor of future relationship. Relationships were shorter when the patient's
      health status was complex and when the patient's care system was smaller.
      CONCLUSIONS: Population health management can be beneficial to the care system
      making this investment, particularly for patients exhibiting prior continuity in
      care system choice. The results suggest that co-located primary and specialty
      services are important in maintaining primary care loyalty.

PMID- 24461031
TI  - Intraoperative radiotherapy for early breast cancer: do health professionals
      choose convenience or risk?
AB  - BACKGROUND: The randomized TARGIT trial comparing experimental intra-operative
      radiotherapy (IORT) to up to 7 weeks of daily conventional external beam
      radiotherapy (EBRT) recruited participants in Western Australia between 2003 and
      2012. We aimed to understand preferences for this evolving radiotherapy treatment
      for early breast cancer (EBC) in health professionals, and how they changed over
      time and in response to emerging data. Preferences for single dose IORT or EBRT
      for EBC were elicited in 2004 and 2011, together with factors that may be
      associated with these preferences. METHODS: Western Australian health
      professionals working with breast cancer patients were invited to complete a
      validated, self-administered questionnaire. The questionnaire used hypothetical
      scenarios and trade-off methodology to determine the maximum increase in risk of
      local recurrence health professionals were willing to accept in order to have a
      single dose of IORT in the place of EBRT if they were faced with this decision
      themselves. RESULTS: Health professional characteristics were similar across the
      two time points although 2011 included a higher number of nurse (49% vs. 36%) and
      allied health (10% vs. 4%) participants and a lower number of radiation
      therapists (17% vs. 32% ) compared to 2004.Health professional preferences
      varied, with 7.5% and 3% judging IORT unacceptable at any risk, 18% and 21%
      judging IORT acceptable only if offering an equivalent risk, 56% and 59% judging
      IORT acceptable with a low maximum increase in risk (1-3%) and 19% and 17%
      judging a high maximum increase in risk acceptable (4-5%), in 2004 and 2011
      respectively. A significantly greater number of nurses accepted IORT as a
      treatment option in 2011. CONCLUSIONS: Most Western Australian health
      professionals working with breast cancer patients are willing to accept an
      increase in risk of local recurrence in order to replace EBRT with IORT in a
      hypothetical setting. This finding was consistent over two time points spanning 7
      years despite the duration of clinical experience with IORT and the publication
      of the early clinical results of IORT in 2010. These results need to be compared
      with preferences elicited from patient groups, and further investigation into the
      impact of personal preferences on health professionals' advice to patients is
      warranted.

PMID- 24461032
TI  - Temporal trends in epilepsy surgery.

PMID- 24461033
TI  - Editorial. Veterinary Dermatology Journal celebrates 25 years.

PMID- 24461034
TI  - Agreement between allergen-specific IgE assays and ensuing immunotherapy
      recommendations from four commercial laboratories in the USA.
AB  - BACKGROUND: Canine allergen-specific IgE assays in the USA are not subjected to
      an independent laboratory reliability monitoring programme.
      HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the agreement of
      diagnostic results and treatment recommendations of four serum IgE assays
      commercially available in the USA. METHODS: Replicate serum samples from 10
      atopic dogs were submitted to each of four laboratories for allergen-specific IgE
      assays (ACTT((r)) , VARL Liquid Gold, ALLERCEPT((r)) and Greer((r)) Aller-g
      complete((r)) ). The interlaboratory agreement of standard, regional panels and
      ensuing treatment recommendations were analysed with the kappa statistic (kappa)
      to account for agreement that might occur merely by chance. Six comparisons of
      pairs of laboratories and overall agreement among laboratories were analysed for
      ungrouped allergens (as tested) and also with allergens grouped according to
      reported cross-reactivity and taxonomy. RESULTS: The overall chance-corrected
      agreement of the positive/negative test results for ungrouped and grouped
      allergens was slight (kappa = 0.14 and 0.13, respectively). Subset analysis of
      the laboratory pair with the highest level of diagnostic agreement (kappa = 0.36)
      found slight agreement (kappa = 0.13) for ungrouped plants and fungi, but
      substantial agreement (kappa = 0.71) for ungrouped mites. The overall agreement
      of the treatment recommendations was slight (kappa = 0.11). Altogether, 85.1% of
      ungrouped allergen treatment recommendations were unique to one laboratory or
      another. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study indicated that the choice
      of IgE assay may have a major influence on the positive/negative results and
      ensuing treatment recommendations.

PMID- 24461035
TI  - Multiple trichoblastomas in a dog.
AB  - BACKGROUND: Hair follicle tumours generally present as benign, solitary masses
      and have a good prognosis following surgical resection. HYPOTHESIS/OBJECTIVES:
      This report describes a case of multiple trichoblastomas in a dog. ANIMAL: A 2
      year-old crossbred dog presented with multiple soft cutaneous periocular,
      perilabial, submandibular and nasal nodules, between 2 and 9 cm in diameter,
      located on the right side of the face. New nodules were observed on the same side
      of the face at a second consultation 3 weeks later. METHODS: Surgical resection
      of all nodules was performed in two procedures. Three nodules were initially
      resected and submitted for histolopathology and immunohistochemistry. The
      diagnosis was trichoblastoma for all three. At the time of the second
      consultation, new and remaining nodules were biopsied and the diagnosis of
      trichoblastoma confirmed. The dog was treated with doxorubicin and piroxicam for
      30 days prior to the second surgical procedure in an attempt to reduce new tumour
      growth and the size of present tumours. All nodules were resected and the defects
      closed using rotation flaps. RESULTS: No recurrence of the neoplasm was noted
      within 10 months after surgery. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Trichoblastomas are generally benign but can present as multiple neoplasms that
      may require surgical resection and may respond to chemotherapy. To the authors'
      knowledge, this is the first report of multiple trichoblastomas in a dog.

PMID- 24461036
TI  - Atypical canine recurrent alopecia.

PMID- 24461037
TI  - Evaluation of X-ray microanalysis for characterization of dental enamel.
AB  - Elemental analysis of dental hard tissues is of importance. The aim of this study
      is to evaluate X-ray microanalysis (XRMA) of bovine enamel in a scanning electron
      microscope (SEM) with different coatings. The buccal surface of bovine incisors
      was polished flat, one-third was coated with carbon, one-third with gold, leaving
      one-third uncoated for XRMA in an SEM equipped with an energy-dispersive
      microanalysis system. The elements oxygen, sodium, magnesium, phosphorous,
      chlorine, potassium, and calcium were analyzed using their respective
      characteristic K X-ray series. Comparisons were made with analyses of glass
      produced by fusion of the bovine enamel, showing that oxygen analyses using the K
      X-ray series are reliable and preferable to calculating oxygen by stoichiometry
      for natural enamel. For the gold-coated and uncoated analyses, carbon was also
      measured using the K X-ray series. Small area Analyses in small areas (80 * 80
      MUm) in variable pressure-SEM mode with low vacuum (20 Pa), without any coating,
      midway between 40 MUm wide gold lines 140 MUm apart to avoid build-up of
      electrostatic charge is the preferred method, especially if carbon is included in
      the analysis. The analyses of bovine enamel are sufficiently reproducible to be
      regarded as quantitative for all elements except carbon. 

PMID- 24461038
TI  - Case fatality ratio and mortality rate trends of community-onset Staphylococcus
      aureus bacteraemia.
AB  - Lethal outcomes can be expressed as a case fatality ratio (CFR) or as a mortality
      rate per 100 000 population per year (MR). Population surveillance for community
      onset methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)
      Staphylococcus aureus bacteraemia was conducted in Canada, Australia, Sweden and
      Denmark to evaluate 30-day CFR and MR trends between 2000 and 2008. The CFR was
      20.3% (MSSA 20.2%, MRSA 22.3%) and MR was 3.4 (MSSA 3.1, MRSA 0.3) per 100 000
      per year. Although MSSA CFR was stable the MSSA MR increased; MRSA CFR decreased
      while its MR remained low during the study. Community-onset S. aureus
      bacteraemia, particularly MSSA, is associated with major disease burden. This
      study highlights complementary information provided by evaluating both CFR and
      MR.

PMID- 24461039
TI  - Stratifying the risk of facial nerve palsy after benign parotid surgery.
AB  - INTRODUCTION: Post-operative facial palsy is the most important potential
      complication of parotid surgery for benign lesions. The published prevalence of
      facial weakness is up to 57 per cent for temporary weakness and up to 7 per cent
      for permanent weakness. We aimed to identify potential risk factors for post
      operative facial palsy. MATERIALS AND METHODS: One hundred and fifty patients who
      had undergone parotid surgery for benign disease were retrospectively reviewed.
      Tumour factors (size, location and histopathology), patient factors (age and sex)
      and operative factors (operation, surgeon grade, surgeon specialty and use of
      intra-operative facial nerve monitoring) were all analysed for significant
      associations with post-operative facial palsy. RESULTS AND ANALYSIS: The overall
      incidence of facial palsy was 26.7 per cent for temporary weakness and 2.6 per
      cent for permanent weakness. The associations between facial palsy and all the
      above factors were analysed using Pearson's chi-square test and found to be non
      significant. CONCLUSION: These outcomes compare favourably with the literature.
      No significant risk factors were identified, suggesting that atraumatic,
      meticulous surgical technique is still the most important factor affecting post
      operative facial palsy.

PMID- 24461040
TI  - Context, as well as inputs, shape decisions, but are people aware of it?
AB  - Even if people are experts at understanding how various input cues landed them at
      a particular decision (something the authors refer to as cue utilization), they
      may still fail to appreciate how context influences the weight given to those
      input variables. We review evidence suggesting that people are unaware of
      contextual influences on their decisions. 

PMID- 24461041
TI  - Direct and social genetic parameters for growth and fin damage traits in Atlantic
      cod (Gadus morhua).
AB  - BACKGROUND: The aim of the study was to estimate genetic parameters for direct
      and social genetic effects (SGE) for growth and welfare traits in farmed Atlantic
      cod (Gadus morhua). A SGE refers to the effect of an individual's genes on trait
      performance of its social partners. In total, 2100 individually tagged juveniles
      from 100 families at an average age of 222 days post-hatching were used. Each
      family was separated into three groups of seven fish, and were randomly assigned
      to 100 experimental tanks, together with fish from two other families. Body
      weight and length of the first, second and third dorsal fin and the caudal fin
      measured by digital image analysis were measured at the start of the experiment,
      after two weeks, and after six weeks. Fin erosion was scored subjectively after
      six weeks. Variance components estimated using a conventional animal model were
      compared to those of an animal model including a SGE. RESULTS: Heritabilities
      from the conventional animal model ranged from 0.24 to 0.34 for body weight and
      0.05 to 0.80 for fin length. Heritabilities for fin erosion were highest for the
      first dorsal fin (0.83 +/- 0.08, mean +/- standard error) and lowest for the
      third dorsal fin (0.01 +/- 0.04). No significant SGE were found for body weight,
      whereas SGE for fin lengths were significant after two and six weeks.
      Contributions to the total heritable variance were equal to 21.5% (6.1 +/- 2.1)
      for the direct effect, 33.1% (9.4 +/- 3.2) for the direct-social covariance, and
      45.4% (12.9 +/- 4.1) for the social variance for length of the first dorsal fin.
      For fin erosion, SGE were only significant for the second and third dorsal fin.
      CONCLUSIONS: Including SGE for fin length and fin erosion in the animal model
      increased the estimated heritable variation. However, estimates of total
      heritable variances were inaccurate and a larger experiment is needed to
      accurately quantify total heritable variance. Despite this, our results
      demonstrate that considering social breeding values for fin length or fin erosion
      when selecting fish will enable us to improve response to selection for welfare
      traits in Atlantic cod juveniles.

PMID- 24461042
TI  - An exploratory survey measuring stigma and discrimination experienced by people
      living with HIV/AIDS in South Africa: the People Living with HIV Stigma Index.
AB  - BACKGROUND: The continued presence of stigma and its persistence even in areas
      where HIV prevalence is high makes it an extraordinarily important, yet
      difficult, issue to eradicate. The study aimed to assess current and emerging
      HIV/AIDS stigma and discrimination trends in South Africa as experienced by
      people living with HIV/AIDS (PLHIV). METHODS: The PLHIV Stigma Index, a
      questionnaire that measures and detects changing trends in relation to stigma and
      discrimination experienced by PLHIV, was used as the survey tool. The study was
      conducted in 10 clinics in four provinces supported by the Foundation for
      Professional Development (FPD), with an interview total of 486 PLHIV. A cross
      sectional design was implemented in the study, and both descriptive and
      inferential analysis was conducted on the data. RESULTS: Findings suggest that
      PLHIV in this population experience significant levels of stigma and
      discrimination that negatively impact on their health, working and family life,
      as well as their access to health services. Internalised stigma was prominent,
      with many participants blaming themselves for their status. CONCLUSION: The
      findings can be used to develop and inform programmes and interventions to reduce
      stigma experienced by PLHIV. The current measures for dealing with stigma should
      be expanded to incorporate the issues related to health, education and
      discrimination experienced in the workplace, that were highlighted by the study.

PMID- 24461043
TI  - Predominance of Gram-negative bacilli among patients with catheter-related
      bloodstream infections.
AB  - We evaluated changes in the epidemiology of catheter-related bloodstream
      infections (CRBSIs) between 1996 and 2012 in a tertiary care centre in Israel.
      The cohort included 1754 episodes of CRBSI. The incidence of CRBSIs decreased
      throughout the study period, whereas 30-day mortality following bacteraemia
      increased. There was a linear shift toward predominance of Gram-negative bacilli
      throughout the study period (p for trend<0.001). In 1996, 68% (68/100) of CRBSIs
      were caused by Gram-positive cocci, whereas in 2012 77.8% (28/26) were caused by
      Gram-negative bacilli. The shift towards Gram-negative CRBSIs and the associated
      mortality mandates that empirical treatment for CRBSIs be directed by local
      epidemiology.

PMID- 24461044
TI  - Identification of six Listeria species by real-time PCR assay.
AB  - The Listeria genus comprises 10 recognized species. Listeria monocytogenes causes
      listeriosis in humans and other animals primarily via contaminated food or animal
      feed. Listeria ivanovii causes listeriosis in animals and on rare occasions in
      humans. The identification of nonpathogenic species of Listeria in foods
      indicates that conditions exist that support the growth of pathogenic strains and
      is used to facilitate the implementation of control and prevention measures. This
      study shows the development and evaluation of a 5'exonuclease real-time PCR assay
      for the rapid identification of Listeria seeligeri, Listeria welshimeri, L.
      monocytogenes, L. ivanovii, Listeria grayi and Listeria innocua. The assay
      consists of two triplexes that were evaluated using 53 cultures of Gram-positive
      bacteria, including 49 Listeria spp. from human, animal, food or food-processing
      environments. The assay was rapid, specific and reproducible and could identify
      each of the six species from a mixture of strains. The developed assay proved to
      be a powerful means of rapidly identifying Listeria species and could be usefully
      implemented in busy specialist reference laboratories. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The identification of species of Listeria from foods is important to
      monitor pathogenic strains and facilitates the implementation of control
      measures. This study shows the development and evaluation of a 5'exonuclease real
      time PCR assay for the rapid identification of L. seeligeri, L. welshimeri, L.
      monocytogenes and L. ivanovii, L. grayi, L. innocua. The developed assay proved
      to be specific, rapid and reproducible and therefore could be implemented in busy
      specialist reference laboratories.

PMID- 24461045
TI  - Reasons for participation and non-participation in a diabetes prevention trial
      among women with prior gestational diabetes mellitus (GDM).
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for the
      development of type 2 diabetes. Lifestyle intervention can prevent progression to
      type 2 diabetes in high risk populations. We designed a randomised controlled
      trial (RCT) to evaluate the effectiveness of an established lifestyle
      intervention compared to standard care for delaying diabetes onset in European
      women with recent GDM. Recruitment into the RCT was more challenging than
      anticipated with only 89 of 410 (22%) women agreeing to participate. This paper
      identifies factors that could enhance participation of the target population in
      future interventions. METHODS: We hypothesised that women who agreed to
      participate would have higher diabetes risk profiles than those who declined, and
      secondly that it would be possible to predict participation on the bases of those
      risk factors. To test our hypothesis, we identified the subset of women for whom
      we had comprehensive data on diabetes risks factors 3-5 years following GDM,
      reducing the sample to 43 participants and 73 decliners. We considered
      established diabetes risk factors: smoking, daily fruit and vegetable intake,
      participation in exercise, family history of diabetes, glucose values and BMI
      scores on post-partum re-screens, use of insulin during pregnancy, and age at
      delivery. We also analysed narrative data from 156 decliners to further
      understand barriers to and facilitators of participation. RESULTS: Two factors
      differentiated participants and decliners: age at delivery (with women older than
      34 years being more likely to participate) and insulin use during pregnancy (with
      women requiring the use of insulin in pregnancy less likely to participate).
      Binary logistic regression confirmed that insulin use negatively affected the
      odds of participation. The most significant barriers to participation included
      the accessibility, affordability and practicality of the intervention.
      CONCLUSIONS: Women with recent GDM face multiple barriers to lifestyle change.
      Intervention designers should consider: (i) the practicalities of participation
      for this population, (ii) research designs that capitalise on motivational
      differences between participants, (iii) alleviating concerns about long-term
      diabetes management. We hope this work will support future researchers in
      developing interventions that are more relevant, effective and successful in
      recruiting the desired population. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN41202110.

PMID- 24461046
TI  - Intravital imaging in spontaneously hypertensive stroke-prone rats-a pilot study.
AB  - BACKGROUND: There is growing evidence that endothelial failure and subsequent
      blood brain barrier (BBB) breakdown initiate cerebral small vessel disease (CSVD)
      pathology. In spontaneously hypertensive stroke-prone rats (SHRSP) endothelial
      damage is indicated by intraluminal accumulations of erythrocytes (erythrocyte
      thrombi) that are not observed with current magnetic resonance imaging
      techniques. Two-photon microscopy (2 PM) offers the potential for real-time
      direct detection of the small vasculature. Thus, within this pilot study we
      investigated the sensitivity of 2 PM to detect erythrocyte thrombi expressing
      initiating CSVD phenomena in vivo. METHODS: Eight SHRSP and 13 Wistar controls
      were used for in vivo imaging and subsequent histology with haematoxylin-eosin
      (HE). For 2 PM, cerebral blood vessels were labeled by fluorescent Dextran (70
      kDa) applied intraorbitally. The correlation between vascular erythrocyte thrombi
      observed by 2 PM and HE-staining was assessed. Artificial surgical damage and
      parenchymal Dextran distribution were analyzed postmortem. RESULTS: Dextran was
      distributed within the small vessel walls and co-localized with IgG.Artificial
      surgical damage was comparable between SHRSP and Wistar controls and mainly
      affected the small vasculature. In fewer than 20% of animals there was
      correlation between erythrocyte thrombi as observed with 2 PM and histologically
      with HE. CONCLUSIONS: Contrary to our initial expectations, there was little
      agreement between intravital 2 PM imaging and histology for the detection of
      erythrocyte thrombi. Two-photon microscopy is a valuable technique that
      complements but does not replace the value of conventional histology.

PMID- 24461047
TI  - Galantamine treatment in outpatients with mild Alzheimer's disease.
AB  - OBJECTIVE: To assess long-term effectiveness of galantamine in community-dwelling
      persons with mild Alzheimer's disease. METHODS: Prospective open-label trial
      including patients with mild AD (NINCDS-ADRDA criteria) treated with galantamine
      for up to 36 months. Outcome parameters included ADAS-cog/11, Bayer-ADL scale
      (self- and caregivers' ratings), 10-item NPI and CGI-change, safety and
      tolerability measures. Data are presented based on ITT analyses (LOCF). RESULTS:
      Seventy-five patients (55% women; mean ADAS-cog 22.3; mean age 70.2 years) were
      treated with galantamine for approximately 36 months. About 60% (n=45) received a
      total daily dose of 24 mg galantamine at final visit. After 3, 6, and 12 months
      of treatment, mean improvements in ADAS-cog ranged between 2.2 and 3.0 points
      (all P<0.05). After 24-month treatment, ADAS-cog returned to baseline value and
      at 3-year follow-up, patient deteriorated on average by 2.9 points. There was
      significant improvement on the NPI scale between baseline and 3- to 12-month
      follow-up (all P<0.05) and at 3-year endpoint, a slight deterioration was noted.
      Activities of daily living (B-ADL) decreased significantly after 24 months in
      self-ratings and after 12 months in caregivers' ratings. Fifty-four patients
      reported at least one AE, most of them occurring during the first 2 years of
      treatment. Among the most frequently (>10%) reported AEs irrespective of causal
      relationship to study medication were nausea (17.3%), dizziness (12%), and
      vomiting (10.7%). CONCLUSION: Galantamine was generally safe and well tolerated
      during the 3-year observation period. Cognition, behavior, and activities of
      daily living improved during 12 months treatment. At 3-year follow-up, worsening
      in all outcomes was measured; however, cognition remained improved compared with
      an untreated population.

PMID- 24461048
TI  - Fast, simple, and informative patient-specific dose verification method for
      intensity modulated total marrow irradiation with helical tomotherapy.
AB  - BACKGROUND: Patient-specific dose verification for treatment planning in helical
      tomotherapy is routinely performed using a homogeneous virtual water cylindrical
      phantom of 30 cm diameter and 18 cm length (Cheese phantom). Because of this
      small length, treatment with total marrow irradiation (TMI) requires multiple
      deliveries of the dose verification procedures to cover a wide range of the
      target volumes, which significantly prolongs the dose verification process. We
      propose a fast, simple, and informative patient-specific dose verification method
      which reduce dose verification time for TMI with helical tomotherapy. METHODS: We
      constructed a two-step solid water slab phantom (length 110 cm, height 8 cm, and
      two-step width of 30 cm and 15 cm), termed the Whole Body Phantom (WB phantom).
      Three ionization chambers and three EDR-2 films can be inserted to cover extended
      field TMI treatment delivery. Three TMI treatment plans were conducted with a
      TomoTherapy HiArt Planning Station and verified using the WB phantom with ion
      chambers and films. Three regions simulating the head and neck, thorax, and
      pelvis were covered in a single treatment delivery. The results were compared to
      those with the cheese phantom supplied by Accuray, Inc. following three treatment
      deliveries to cover the body from head to pelvis. RESULTS: Use of the WB phantom
      provided point doses or dose distributions from head and neck to femur in a
      single treatment delivery of TMI. Patient-specific dose verification with the WB
      phantom was 62% faster than with the cheese phantom. The average pass rate in
      gamma analysis with the criteria of a 3-mm distance-to-agreement and 3% dose
      differences was 94% +/- 2% for the three TMI treatment plans. The differences in
      pass rates between the WB and cheese phantoms at the upper thorax to abdomen
      regions were within 2%. The calculated dose agreed with the measured dose within
      3% for all points in all five cases in both the WB and cheese phantoms.
      CONCLUSIONS: Our dose verification method with the WB phantom provides simple and
      rapid quality assurance without limiting dose verification information in total
      marrow irradiation with helical tomotherapy.

PMID- 24461051
TI  - Cutaneous involvement in canine leishmaniosis due to Leishmania infantum (syn. L.
      chagasi).
AB  - BACKGROUND: Canine leishmaniosis, a zoonotic infectious disease caused by
      Leishmania infantum (syn. L. chagasi), is fairly common in endemic areas, and
      skin lesions are the most frequent clinical manifestation. Despite the large
      volume of relevant scientific information, there is a relative paucity of up-to
      date review articles on the cutaneous manifestations of the disease.
      HYPOTHESIS/OBJECTIVES: This review provides current information on the
      macroscopic and histological skin lesions of dogs with leishmaniosis and comments
      on their pathogenesis and definitive diagnosis. METHODS: Published articles have
      been thoroughly reviewed and the retrieved information has been used and
      supplemented as appropriate with the authors' clinical experience. RESULTS: The
      main clinicopathological presentations of canine leishmaniosis are exfoliative,
      ulcerative, nodular, sterile pustular and papular dermatitis and nodules at the
      site of parasite inoculation. Histopathology is usually dominated by mononuclear
      inflammatory infiltrates; immunohistochemical findings are variable, and
      Leishmania amastigotes are present in both diseased and normal-looking skin of
      dogs with leishmaniosis. Definitive diagnosis of the skin lesions in a dog with
      leishmaniosis is based on their macroscopic appearance, exclusion of main
      differentials, histopathology, demonstration of the parasite in the skin and
      complete response to antileishmanial treatment. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Canine leishmaniosis due to L. infantum is characterized by diverse
      cutaneous manifestations that may reflect different host-parasite relationships.
      Furthermore, different types of skin lesions may occur, in various combinations,
      in the same dog. The definitive diagnosis of these lesions is based on clinical
      and laboratory examinations and on the response to antileishmanial treatment.

PMID- 24461049
TI  - Surgical quality is more than volume: the association between changing urologists
      and complications for patients with localized prostate cancer.
AB  - OBJECTIVES: To examine the association of changing urologists on surgical
      complications in men with prostate cancer. DATA SOURCES/STUDY SETTING: Registry
      and administrative claims data from the Surveillance, Epidemiology, and End
      Results-Medicare database from 1995 to 2005. STUDY DESIGN: A cross-sectional
      observational study of men with prostate cancer who underwent radical
      prostatectomy. METHODS: Subjects were classified as having "changed urologists"
      if they had a different urologist who diagnosed their cancer from the one who
      performed their surgery. "Doubly robust" propensity score weighted multivariable
      logistic regression models were used to investigate the effect of changing
      urologists on 30-day surgical complications, late urinary complications, and long
      term incontinence. PRINCIPAL FINDINGS: Men who changed urologists between
      diagnosis and treatment had significantly lower odds of 30-day surgical
      complications compared with men who did not change urologists (odds ratio: 0.82;
      95 percent confidence interval: 0.76-0.89), after adjustment. Changing urologists
      was associated with lower risks of 30-day complications for both black and white
      men compared with staying with the same urologist for their diagnosis and
      surgical treatment. CONCLUSIONS: Urologist changing is associated with the
      observed variation in complications following radical prostatectomy. This may
      suggest that patients are responding to aspects of surgical quality not captured
      in surgical volume.

PMID- 24461052
TI  - Relationship of EMG/SMG features and muscle strength level: an exploratory study
      on tibialis anterior muscles during plantar-flexion among hemiplegia patients.
AB  - BACKGROUND: Improvement in muscle strength is an important aim for the
      rehabilitation of hemiplegia patients. Presently, the rehabilitation prescription
      depends on the evaluation results of muscle strength, which are routinely
      estimated by experienced physicians and therefore not finely quantitative. Widely
      used quantification methods for disability, such as Barthel Index (BI) and motor
      component of Functional Independent Measure (M-FIM), yet have limitations in
      their application, since both of them differentiated disability better in lower
      than higher disability, and they are subjective and recorded in wide scales. In
      this paper, to explore finely quantitative measures for evaluation of muscle
      strength level (MSL), we start with the study on quantified electromyography
      (EMG) and sonomyography (SMG) features of tibialis anterior (TA) muscles among
      hemiplegia patients. METHODS: 12 hemiplegia subjects volunteered to perform
      several sets of plantar-flexion movements in the study, and their EMG signals and
      SMG signals were recorded on TA independently to avoid interference. EMG data
      were filtered and then the root-mean-square (RMS) was computed. SMG signals,
      specifically speaking, the muscle thickness of TA, were manually measured by two
      experienced operators using ultrasonography. Reproducibility of the SMG
      assessment on TA between operators was evaluated by non-parametric test
      (independent sample T test). Possible relationship between muscle thickness
      changes (TC) of TA and muscle strength level of hemiplegia patients was
      estimated. RESULTS: Mean of EMG RMS between subjects is found linearly correlated
      with MSL (R2 = 0.903). And mean of TA muscle TC amplitudes is also linearly
      correlated with MSL among dysfunctional legs (R2 = 0.949). Moreover, rectified TC
      amplitudes (dysfunctional leg/ healthy leg, DLHL) and rectified EMG signals
      (DLHL) are found in linear correlation with MSL, with R2 = 0.756 and R2 = 0.676
      respectively. Meanwhile, the preliminary results demonstrate that patients' peak
      values of TC are generally proportional to their personal EMG peak values in 12
      dysfunctional legs and 12 healthy legs (R2 = 0.521). CONCLUSIONS: It's concluded
      that SMG could be a promising option to quantitatively estimate MSL for
      hemiplegia patients during rehabilitation besides EMG. However, after this
      exploratory study, they should be further investigated on a larger number of
      subjects.

PMID- 24461053
TI  - Cardiovascular magnetic resonance risk stratification in patients with clinically
      suspected myocarditis.
AB  - BACKGROUND: The diagnosis of myocarditis is challenging due to its varying
      clinical presentation. Since myocarditis can be associated with significant 5
      year mortality, and postmortem data show myocarditis in almost 10% of all adults
      suffering sudden cardiac death, individual risk stratification for patients with
      suspected myocarditis is of great clinical interest. We sought to demonstrate
      that patients with clinically suspected myocarditis and a normal cardiovascular
      magnetic resonance (CMR) according to our definition have a good prognosis,
      independent of their clinical symptoms and other findings. METHODS: Prospective
      clinical long-term follow-up of consecutive patients undergoing CMR for work-up
      of clinically suspected myocarditis at our institution in 2007-2008. RESULTS:
      Follow-up was available for n=405 patients (all-comers, 54.8% inpatients, 38%
      outpatient referrals from cardiologists). Median follow-up time was 1591 days.
      CMR diagnosis was "myocarditis" in 28.8%, "normal" in 55.6% and "other pathology"
      in 15.6%. Normal CMR was defined as normal left ventricular (LV) volumes and
      normal left ventricular ejection fraction (LV-EF) in the absence of late
      Gadolinium Enhancement (LGE). The overall mortality was 3.2%. There were seven
      cardiac deaths during follow-up, in addition one aborted SCD and two patients had
      appropriate internal cardioverter defibrillator (ICD) shocks - all of these
      occurred in patients with abnormal CMR. Kaplan-Meier analysis with log-rank test
      showed significant difference for major adverse cardiac events (cardiac death,
      sudden cardiac death (SCD), ICD discharge, aborted SCD) between patients with
      normal and abnormal CMR (p=0.0003). CONCLUSION: In our unselected population of
      consecutive patients referred for CMR work-up of clinically suspected
      myocarditis, patients with normal CMR have a good prognosis independent of their
      clinical symptoms and other findings.

PMID- 24461054
TI  - Methicillin-susceptible Staphylococcus aureus clonal complex 398: high prevalence
      and geographical heterogeneity in bone and joint infection and nasal carriage.
AB  - The prevalence of clonal complex (CC) 398 methicillin-susceptible Staphylococcus
      aureus (MSSA) was unexpectedly high among bone and joint infections (BJIs) and
      nasal-colonizing isolates in France, with surprising geographical heterogeneity.
      With none of the major, most-known staphylococcal virulence genes, MSSA CC398 BJI
      was associated with lower biological inflammatory syndrome and lower treatment
      failure rates.

PMID- 24461055
TI  - Mobile elements and mitochondrial genome expansion in the soil fungus and potato
      pathogen Rhizoctonia solani AG-3.
AB  - The soil fungus Rhizoctonia solani is an economically important pathogen of
      agricultural and forestry crops. Here, we present the complete sequence and
      analysis of the mitochondrial genome of R. solani, field isolate Rhs1AP. The
      genome (235 849 bp) is the largest mitochondrial genome of a filamentous fungus
      sequenced to date and exhibits a rich accumulation of introns, novel repeat
      sequences, homing endonuclease genes, and hypothetical genes. Stable secondary
      structures exhibited by repeat sequences suggest that they comprise functional,
      possibly catalytic RNA elements. RNA-Seq expression profiling confirmed that the
      majority of homing endonuclease genes and hypothetical genes are
      transcriptionally active. Comparative analysis suggests that the mitochondrial
      genome of R. solani is an example of a dynamic history of expansion in
      filamentous fungi.

PMID- 24461056
TI  - First bite syndrome: our experience of laser tympanic plexus ablation.
AB  - INTRODUCTION: First bite syndrome is a condition characterised by severe facial
      pain brought on by the first bite of each meal. This can severely affect the
      patient's ability to eat. METHODS: We present a 70-year-old woman for whom we
      performed a laser ablation of the left ear tympanic plexus, as treatment of first
      bite syndrome. A permeatal approach was used to raise a tympanomeatal flap. The
      tympanic plexus was identified on the promontory and a 4 mm2 area of the plexus
      was ablated using CO2 laser. The flap was repositioned and a dressing was placed
      with topical antibiotics. RESULTS: At two-month follow up, there was full
      resolution of the patient's symptoms. DISCUSSION: First bite syndrome carries a
      high morbidity; treatment options are variable, and often unsuccessful. We
      describe the first documented case of laser tympanic plexus ablation, with a very
      effective initial response. This procedure represents a useful therapeutic option
      for first bite syndrome.

PMID- 24461057
TI  - A Monte Carlo simulation study comparing linear regression, beta regression,
      variable-dispersion beta regression and fractional logit regression at recovering
      average difference measures in a two sample design.
AB  - BACKGROUND: In biomedical research, response variables are often encountered
      which have bounded support on the open unit interval--(0,1). Traditionally,
      researchers have attempted to estimate covariate effects on these types of
      response data using linear regression. Alternative modelling strategies may
      include: beta regression, variable-dispersion beta regression, and fractional
      logit regression models. This study employs a Monte Carlo simulation design to
      compare the statistical properties of the linear regression model to that of the
      more novel beta regression, variable-dispersion beta regression, and fractional
      logit regression models. METHODS: In the Monte Carlo experiment we assume a
      simple two sample design. We assume observations are realizations of independent
      draws from their respective probability models. The randomly simulated draws from
      the various probability models are chosen to emulate average
      proportion/percentage/rate differences of pre-specified magnitudes. Following
      simulation of the experimental data we estimate average
      proportion/percentage/rate differences. We compare the estimators in terms of
      bias, variance, type-1 error and power. Estimates of Monte Carlo error associated
      with these quantities are provided. RESULTS: If response data are beta
      distributed with constant dispersion parameters across the two samples, then all
      models are unbiased and have reasonable type-1 error rates and power profiles. If
      the response data in the two samples have different dispersion parameters, then
      the simple beta regression model is biased. When the sample size is small (N0 =
      N1 = 25) linear regression has superior type-1 error rates compared to the other
      models. Small sample type-1 error rates can be improved in beta regression models
      using bias correction/reduction methods. In the power experiments, variable
      dispersion beta regression and fractional logit regression models have slightly
      elevated power compared to linear regression models. Similar results were
      observed if the response data are generated from a discrete multinomial
      distribution with support on (0,1). CONCLUSIONS: The linear regression model, the
      variable-dispersion beta regression model and the fractional logit regression
      model all perform well across the simulation experiments under consideration.
      When employing beta regression to estimate covariate effects on (0,1) response
      data, researchers should ensure their dispersion sub-model is properly specified,
      else inferential errors could arise.

PMID- 24461058
TI  - Automatic processes, emotions, and the causal field.
AB  - Newell & Shanks (N&S) provide a welcome examination of many claims about
      unconscious influences on decision making. I emphasize two issues that they do
      not consider fully: the roles of automatic processes and emotions. I further
      raise an important conceptual problem in assigning causes to potential
      unconscious influences. Which "causal field" is relevant: that of the
      investigator or the experimental participants? 

PMID- 24461059
TI  - The p53 mutation spectrum in hepatocellular carcinoma from Guangxi, China : role
      of chronic hepatitis B virus infection and aflatoxin B1 exposure.
AB  - BACKGROUND & AIMS: p53 is one of the most frequently mutated human tumour
      suppressor genes. Chronic infection with hepatitis B virus (HBV) and exposure to
      aflatoxin B1 (AFB1) induces p53 mutations in hepatocellular carcinoma (HCC)
      tissue. The aims of present study are to investigate the p53 mutation spectrum in
      HBV- and AFB1-related hepatocarcinogenesis in patients with hepatocellular
      carcinoma (HCC) in Guangxi, China. METHODS: Tumour and adjacent liver tissue were
      collected from 397 HCC patients who were subdivided into HBV(+)/AFB1(+),
      HBV(+)/AFB1(-), HBV(-)/AFB1(+) and HBV(-)/AFB1(-) four groups. All 11 exons of
      the p53 gene were PCR-amplified and sequenced. Immunohistochemistry was used to
      evaluate the effect of mutations on the expression of p53 protein. RESULTS AND
      CONCLUSIONS: P53 mutations were detected in 223 HCC samples, 13 adjacent liver
      tissue samples and only 1 of 68 normal liver tissue samples. The mutation sites
      concentrated at exon 4, 5, 6, 7, 8, 9 and no mutation was detected in exon 1, 2,
      3, 10 and 11. The most frequently occurring mutation was in codon 249 (R249S) in
      exon 7. Patients in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups had
      significantly higher mutation rates compared with patients in the HBV(+)/AFB1(-)
      and HBV(-)/AFB1(-) groups. P53 mutation status and HBV/AFB1 status were
      independent predictors of tumour recurrence after surgery. Immunohistochemical
      analysis revealed that p53 gene mutations were correlated with the p53
      expression. In Guangxi area, the significant association between AFB1-induced p53
      mutations and the expression of p53 protein suggest an important role for p53
      mutations in carcinogenesis of HCC.

PMID- 24461060
TI  - Statistical tools to improve assessing agreement between several observers.
AB  - In the context of assessing the impact of management and environmental factors on
      animal health, behaviour or performance it has become increasingly important to
      conduct (epidemiological) studies in the field. Hence, the number of investigated
      farms per study is considerably high so that numerous observers are needed for
      investigation. In order to maintain the quality and validity of study results
      calibration meetings where observers are trained and the current level of
      agreement is assessed have to be conducted to minimise the observer effect. When
      study animals were rated independently by the same observers by a categorical
      variable the exclusion test can be performed to identify disagreeing observers.
      This statistical test compares for each variable and each observer the observer
      specific agreement with the overall agreement among all observers based on kappa
      coefficients. It accounts for two major challenges, namely the absence of a gold
      standard observer and different data type comprising ordinal, nominal and binary
      data. The presented methods are applied on a reliability study to assess the
      agreement among eight observers rating welfare parameters of laying hens. The
      degree to which the observers agreed depended on the investigated item (global
      weighted kappa coefficients: 0.37 to 0.94). The proposed method and graphical
      description served to assess the direction and degree to which an observer
      deviates from the others. It is suggested to further improve studies with
      numerous observers by conducting calibration meetings and accounting for observer
      bias. 

PMID- 24461062
TI  - The music of the genes.

PMID- 24461061
TI  - Anticancer effects of pyocyanin on HepG2 human hepatoma cells.
AB  - Pyocyanin, a major virulence factor produced by Pseudomonas aeruginosa, displays
      redox activity and damaging effects on mammalian cells. In this study, we
      investigated the effects of pyocyanin on the proliferation of HepG2 tumour cells.
      Interestingly, pyocyanin significantly inhibited cell proliferation and triggered
      the production of large amounts of reactive oxygen species (ROS), thereby
      upregulating superoxide dismutase (SOD) and catalase (CAT). Additionally,
      pyocyanin treatment significantly depleted reduced glutathione (GSH) and
      decreased the GSH/oxidized GSH (GSSG) ratio. These results supported that
      pyocyanin-induced cytotoxicity in HepG2 cells was mediated by acute ROS
      production and subsequent oxidative stress. SA-beta-Gal, acridine orange
      (AO)/ethidium bromide (EB) double staining, caspase-3 measurements and comet
      assay results revealed that cell death induced by pyocyanin involved DNA damage
      and activation of caspase-3, accelerating cell senescence and apoptosis. Thus,
      our data provided insights into the mechanisms underlying pyocyanin-induced
      cytotoxicity and may lead to better treatment strategies for cancer. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Pyocyanin is a redox-active phenazine toxin. Here, we
      investigated the ability of pyocyanin to inhibit cancer-related phenotypes in
      HepG2 human hepatoma cells. Our results indicated that pyocyanin accelerated
      cellular senescence and apoptosis and induced oxidative stress-associated DNA
      damage in HepG2 cells. The potential anticancer applications of pyocyanin should
      be investigated further in clinical studies.

PMID- 24461063
TI  - Impact of neoadjuvant chemotherapy with PELF-protocoll versus surgery alone in
      the treatment of advanced gastric carcinoma.
AB  - BACKGROUND: In a retrospective study we analyzed the impact of neoadjuvant
      chemotherapy (CTx) with the PELF - protocol (Cisplatin, Epirubicin, Leukovorin, 5
      Fluoruracil) on mortality, recurrence and prognosis of patients with advanced
      gastric carcinoma, UICC stages Ib-III. METHODS: 64 patients were included. 26
      patients received neoadjuvant CTx followed by surgical resection, 38 received
      surgical resection only. Tumor staging was performed by endoscopy,
      endosonography, computed tomography and laparoscopy. Patients staged Ib - III
      received two cycles of CTx according to the PELF-protocol. Adjuvant chemotherapy
      was not performed at all. RESULTS: Complete (CR) or partial response (PR) was
      seen in 20 patients (77%), 19% showing CR and 58% PR. No benefit was observed in
      6 patients (23%). Two of these 6 patients displayed tumor progression during CTx.
      Major toxicity was defined as grade 3 to 4 neutropenia or gastrointestinal side
      effects. One patient died under CTx because of neutropenia and was excluded from
      the overall patient collective. The curative resection rate was 77% after CTx and
      74% after surgery only. The perioperative morbidity rate after CTx was 39% versus
      66% after resection only. Recurrence rate after CTx was 38% and 61% after surgery
      alone; we detected an effective reduction of locoregional recurrence (12% vs.
      26%). The overall survival was 38% after CTx and 42% after resection only. The 5
      year survival rates were 45% in responders, 20% in non - responders and 42% in
      only resected patients. A subgroup analysis indicates that responders with stage
      III tumors may benefit with respect to their 5-year survival in comparable
      patients without neoadjuvant CTx. As to be expected, non-responders with stage
      III tumors did not benefit with respect to their survival. The 5-year-survival
      was approximated using a Kaplan-Meier curve and compared using a log-rank test.
      CONCLUSION: In patients with advanced gastric carcinoma, neoadjuvant CTx with the
      PELF- protocol significantly reduces the recurrence rate, especially
      locoregionally, compared to surgery alone. In our study, there was no overall
      survival benefit after a 5-year follow-up period. Alone a subgroup of patients
      with stage III tumors appear to benefit significantly in the long term from
      neoadjuvant CTx.

PMID- 24461064
TI  - Suppression of LUBAC-mediated linear ubiquitination by a specific interaction
      between LUBAC and the deubiquitinases CYLD and OTULIN.
AB  - Linear ubiquitin chains generated by the linear ubiquitin chain assembly complex
      (LUBAC) play an important role in NF-kappaB activation. However, the regulation
      of linear ubiquitin chain generation by LUBAC is not well characterized. Here, we
      identified two deubiquitinating enzymes (DUBs), ovarian tumor DUB with linear
      linkage specificity (OTULIN/Gumby/FAM105B) and cylindromatosis (CYLD) that can
      cleave linear polyubiquitin chains and interact with LUBAC via the N-terminal
      PNGase/UBA or UBX (PUB) domain of HOIP, a catalytic subunit of LUBAC. HOIP
      interacts with both CYLD and OTULIN even in unstimulated cells. The interaction
      of CYLD and OTULIN with HOIP synergistically suppresses LUBAC-mediated linear
      polyubiquitination and NF-kappaB activation. Moreover, introduction of a HOIP
      mutant unable to bind either deubiquitinase into HOIP-null cells augments the
      activation of NF-kappaB by TNF-alpha stimulation. Thus, the interactions between
      these two deubiquitinases and the LUBAC ubiquitin ligase are involved in
      controlling the extent of TNF-alpha-induced NF-kappaB activation in cells by fine
      tuning the generation of linear ubiquitin chains by LUBAC. The interaction of
      HOIP with OTULIN is also involved in OTULIN suppressing the canonical Wnt
      signaling pathway activation by LUBAC. Our observations provide molecular
      insights into the roles of ligase-deubiquitinase interactions in regulating
      molecular events resulting from linear ubiquitin conjugation. 

PMID- 24461065
TI  - Cesareans, more cesareans and other topics.

PMID- 24461066
TI  - The reduction in fetal death rates; a result of improved identification of high
      risk pregnancies?

PMID- 24461067
TI  - Simulator training and non-technical factors improve laparoscopic performance
      among OBGYN trainees.
AB  - OBJECTIVE: To investigate how simulator training and non-technical factors affect
      laparoscopic performance among residents in obstetrics and gynecology. DESIGN: In
      this prospective study, trainees were randomized into three groups. The first
      group was allocated to proficiency-based training in the LapSimGyn((r)) virtual
      reality simulator. The second group received additional structured mentorship
      during subsequent laparoscopies. The third group served as control group. At
      baseline an operation was performed and visuospatial ability, flow and self
      efficacy were assessed. All groups subsequently performed three tubal occlusions.
      Self-efficacy and flow were assessed before and/or after each operation. SETTING:
      Simulator training was conducted at the Center for Advanced Medical Simulation
      and Training, Karolinska University Hospital. Sterilizations were performed at
      each trainee's home clinic. POPULATION: Twenty-eight trainees/residents from 21
      hospitals in Sweden were included. METHODS/MAIN OUTCOME MEASURES: Visuospatial
      ability was tested by the Mental Rotation Test-A. Flow and self-efficacy were
      assessed by validated scales and questionnaires. Laparoscopic performance was
      measured as the duration of surgery. Visuospatial ability, self-efficacy and flow
      were correlated to the laparoscopic performance using Spearman's correlations.
      Differences between groups were analyzed by the Mann-Whitney U-test. RESULTS: No
      differences across groups were detected at baseline. Self-efficacy scores before
      and flow scores after the third operation were significantly higher in the
      trained groups. Duration of surgery was significantly shorter in the trained
      groups. Flow and self-efficacy correlate positively with laparoscopic
      performance. CONCLUSIONS: Simulator training and non-technical factors appear to
      improve the laparoscopic performance among trainees/residents in obstetrics and
      gynecology.

PMID- 24461068
TI  - Ciclosporin-responsive sterile pustular dermatitides in two dogs.

PMID- 24461069
TI  - Endoscopic duodenal perforation: surgical strategies in a regional centre.
AB  - BACKGROUND: Duodenal perforation is an uncommon complication of endoscopic
      retrograde cholangio-pancreatography (ERCP) and a rare complication of upper
      gastrointestinal endoscopy. Most are minor perforations that settle with
      conservative management. A few perforations however result in life-threatening
      retroperitoneal necrosis and require surgical intervention. There is a relative
      paucity of references specifically describing the surgical interventions required
      for this eventuality. METHODS: Five cases of iatrogenic duodenal perforation were
      ascertained between 2002 and 2007 at Cairns Base Hospital. Clinical features were
      analyzed and compared, with reference to a review of ERCP at that institution for
      the years 2005/2006. RESULTS: One patient recovered with conservative management.
      Of the other four, one died after initial laparotomy. The other three survived,
      undergoing multiple procedures and long inpatient stays. CONCLUSIONS: Iatrogenic
      duodenal perforation with retroperitoneal necrosis is an uncommon complication of
      endoscopy, but when it does occur it is potentially life-threatening. Early
      recognition may lead to a better outcome through earlier intervention, although a
      protracted course with multiple procedures should be anticipated. A number of
      surgical techniques may need to be employed according to the individual
      circumstances of the case.

PMID- 24461070
TI  - Immunogenicity of IMS 1113 plus soluble subunit and chimeric proteins containing
      Mycoplasma hyopneumoniae P97 C-terminal repeat regions.
AB  - The surface adhesin P97 mediates the adherence of Mycoplasma hyopneumoniae to
      swine cilia. Two reiterated repeats R1 and R2 are located at the C-terminus of
      P97. The purpose of this study was to evaluate the immunogenicity of Montanide
      adjuvant IMS 1113 plus soluble subunit proteins rR1, rR1R2 and their chimeric
      forms coupled with B subunit of the heat-labile enterotoxin of Escherichia coli
      (LTB). Each recombinant protein in this study was capable of eliciting anti-R1
      specific humoral antibodies (IgG), mucosal antibodies (IgG and IgA) and IFN-gamma
      production. The chimeric protein rLTBR1R2 elicited the quickest humoral antibody
      response among the recombinant proteins. Serum and bronchoalveolar lavage
      analysis revealed that each recombinant protein was capable of inducing both Th1
      and Th2 responses. Importantly, all of the proteins induced an anti-R1-specific
      Th2-biased response in both humoral and mucosal compartments, similar to the
      response observed in a natural infection or vaccination process. These
      observations indicate that rR1, rR1R2, rLTBR1 and rLTBR1R2 with IMS 1113 might
      represent a promising subunit vaccine strategy against porcine enzootic pneumonia
      in pigs.

PMID- 24461071
TI  - Statistical benchmarks for health care provider performance assessment: a
      comparison of standard approaches to a hierarchical Bayesian histogram-based
      method.
AB  - OBJECTIVE: Examine how widely used statistical benchmarks of health care provider
      performance compare with histogram-based statistical benchmarks obtained via
      hierarchical Bayesian modeling. DATA SOURCES: Publicly available data from 3,240
      hospitals during April 2009-March 2010 on two process-of-care measures reported
      on the Medicare Hospital Compare website. STUDY DESIGN: Secondary data analyses
      of two process-of-care measures comparing statistical benchmark estimates and
      threshold exceedance determinations under various combinations of hospital
      performance measure estimates and benchmarking approaches. PRINCIPAL FINDINGS:
      Statistical benchmarking approaches for determining top 10 percent performance
      varied with respect to which hospitals exceeded the performance benchmark; such
      differences were not found at the 50 percent threshold. Benchmarks derived from
      the histogram of provider performance under hierarchical Bayesian modeling
      provide a compromise between benchmarks based on direct (raw) estimates, which
      are overdispersed relative to the true distribution of provider performance and
      prone to high variance for small providers, and posterior mean provider
      performance, for which over-shrinkage and under-dispersion relative to the true
      provider performance distribution is a concern. CONCLUSIONS: Given the rewards
      and penalties associated with characterizing top performance, the ability of
      statistical benchmarks to summarize key features of the provider performance
      distribution should be examined.

PMID- 24461072
TI  - Talking about transplantation issues--does it need to be difficult?

PMID- 24461073
TI  - Results of a multinational survey regarding the diagnosis and treatment of
      temporomandibular joint involvement in juvenile idiopathic arthritis.
AB  - BACKGROUND: Temporomandibular joint (TMJ) involvement occurs in up to 80% of
      patients with juvenile idiopathic arthritis (JIA). Currently there are no
      standardized procedures regarding diagnosis and treatment of this common
      complication of JIA. The aim of the study was to assess the current clinical
      practices in many countries regarding diagnosis and treatment of TMJ involvement
      in JIA. Pediatric rheumatologists were asked to fill out a survey with 8 items
      regarding diagnosis and treatment of TMJ involvement. The survey was distributed
      over the worldwide pediatric rheumatology electronic list-serve. Data was
      collected in an Excel spread sheet and analyzed using Excel software. FINDINGS:
      Eighty-seven centers responded to the survey between December 2009 and April
      2010. All responding centers were actively screening for TMJ involvement. All
      centers were screening by physical exam, 85 (97%) by history, and 2 (3%) by
      imaging. Seventy-seven (88%) centers were screening at the first visit and 76
      (87%) at each follow-up visit. If imaging was requested, 77% of the centers
      reported that they asked for MRI, 10% for ultrasound, 9% for CT and 33% for X
      ray. The first line treatment of TMJ arthritis was a non-biologic DMARD in 36%,
      an NSAID in 33%, an intraarticular corticosteroid injection in 26%, and an anti
      TNF agent in 5%. Overall, 57 (65%) of the centers were using intraarticular
      corticosteroid injections as treatment. CONCLUSIONS: TMJ arthritis is common
      among children with JIA. This survey shows that a wide array of diagnostic and
      therapeutic approaches is being employed for TMJ disease in 87 international
      centers. Due to this lack of agreement in how to diagnose and treat this JIA
      complication, we believe that an expert opinion/consensus statement regarding TMJ
      arthritis in JIA will likely benefit patients worldwide.

PMID- 24461074
TI  - Daily stress reactivity and serotonin transporter gene (5-HTTLPR) variation:
      internalizing responses to everyday stress as a possible transdiagnostic
      phenotype.
AB  - BACKGROUND: Recent studies examining the interaction between the 5-HTTLPR locus
      in the serotonin transporter gene and life stress in predicting depression have
      yielded equivocal results, leading some researchers to question whether 5-HTTLPR
      variation indeed regulates depressive responses to stress. Two possible sources
      of inconsistent data in this literature are imprecise stress assessment
      methodologies and a restricted focus on depression phenotypes as the outcome of
      interest, as opposed to transdiagnostic emotional symptoms such as internalizing
      and externalizing dimensions. The present study aimed to address these critical
      limitations in prior research by examining how 5-HTTLPR acts in concert with
      idiographically assessed daily life stress to predict transdiagnostic emotional
      outcomes. RESULTS: One hundred and four healthy young adults genotyped for 5
      HTTLPR reported on their life stress exposure and internalizing and externalizing
      experiences for 14 consecutive days. As hypothesized, daily stress levels were
      associated with severity of internalizing symptoms, but only for 5-HTTLPR S
      allele carriers. Additional analyses revealed that these interactive effects of 5
      HTTLPR and daily life stress on internalizing symptoms extended to both the
      distress and fear subdomains of internalizing symptoms. CONCLUSIONS: Considered
      together, these results support the validity of the 5-HTTLPR stress sensitivity
      hypothesis and suggest for the first time that variation at 5-HTTLPR moderates
      the effects of daily life stress on broadband symptom profiles.

PMID- 24461076
TI  - Primary cesarean delivery rates, by state: results from the revised birth
      certificate, 2006-2012.
AB  - Objectives-This report describes state-specific trends in primary cesarean
      delivery rates from 2006 through 2012 for reporting areas that implemented the
      2003 U.S. Standard Certificate of Live Birth by January 1, 2006, and from 2009
      through 2012 for reporting areas that implemented the 2003 revision by January 1,
      2009. State-specific changes by gestational age are also explored. Methods-Data
      for 2006-2012 are based on 100% of singleton births to residents of the reporting
      areas that implemented the 2003 birth certificate revision by January 1 of each
      year. Results are not generalizable to the entire United States-the reporting
      areas do not represent a random sample of U.S. births. Results-The primary
      cesarean delivery rate for the 2006 reporting area (19 states) increased from
      21.9% in 2006 to 22.4% in 2009, and then declined to 21.9% in 2012. For the 2009
      reporting area (28 states and New York City), the primary cesarean rate declined
      from 22.1% to 21.5% during 2009-2012. Rates for 16 of 29 areas declined during
      2009-2012; the remaining states were unchanged. By gestational age, state
      specific primary cesarean delivery rates at 38 weeks declined for 18 of 29 areas
      from 2009 to 2012; few state-specific changes were observed at other gestational
      ages. The primary cesarean delivery rate for the 38 states, District of Columbia,
      and New York City that were using the revised certificate by January 1, 2012, was
      21.5%. State-specific rates ranged from 12.5% (Utah) to 26.9% (Florida and
      Louisiana). 

PMID- 24461075
TI  - The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in
      vivo by targeting the hypoxia inducible factor-1 pathway.
AB  - BACKGROUND: Although tumor hypoxia poses challenges against conventional cancer
      treatments, it provides a therapeutic target for hypoxia-activated drugs. Here,
      we studied the effect of the hypoxia-activated synthetic quinoxaline di-N-oxide
      DCQ against breast cancer metastasis and identified the underlying mechanisms.
      METHODS: The human breast cancer cell lines MCF-7 (p53 wildtype) and MDA-MB-231
      (p53 mutant) were treated with DCQ under normoxia or hypoxia. Drug toxicity on
      non-cancerous MCF-10A breast cells was also determined. In vitro cellular
      responses were investigated by flow cytometry, transfection, western blotting,
      ELISA and migration assays. The anti-metastatic effect of DCQ was validated in
      the MDA-MB-231 xenograft mouse model. RESULTS: DCQ selectively induced apoptosis
      in both human breast cancer cells preferentially under hypoxia without affecting
      the viability of non-cancerous MCF-10A. Cancer cell death was associated with an
      increase in reactive oxygen species (ROS) independently of p53 and was inhibited
      by antioxidants. DCQ-induced ROS was associated with DNA damage, the
      downregulation of hypoxia inducible factor-1 alpha (HIF-1alpha), and inhibition
      of vascular endothelial growth factor (VEGF) secretion. In MCF-7, HIF-1alpha
      inhibition was partially via p53-activation and was accompanied by a decrease in
      p-mTOR protein, suggesting interference with HIF-1alpha translation. In MDA-MB
      231, DCQ reduced HIF-1alpha through proteasomal-dependent degradation mechanisms.
      HIF-1alpha inhibition by DCQ blocked VEGF secretion and invasion in MCF-7 and led
      to the inhibition of TWIST in MDA-MB-231. Consistently, DCQ exhibited robust
      antitumor activity in MDA-MB-231 breast cancer mouse xenografts, enhanced animal
      survival, and reduced metastatic dissemination to lungs and liver. CONCLUSION:
      DCQ is the first hypoxia-activated drug showing anti-metastatic effects against
      breast cancer, suggesting its potential use for breast cancer therapy.

PMID- 24461077
TI  - High-content analysis/screening for predictive toxicology: application to
      hepatotoxicity and genotoxicity.
AB  - High-content imaging/analysis has emerged as a powerful tool for predictive
      toxicology as it can be used for identifying and mitigating potential safety
      risks during drug discovery. By careful selection of end-points, some cellular
      assays can show better predictivity than routine animal toxicity testing for
      certain adverse events. Here, we present the perhaps most utilized high-content
      screening assays for predictive toxicology in the pharmaceutical industry. Multi
      parametric imaging of cell health in simple and cost-effective model systems can
      be used to predict human hepatotoxicity and elucidate mechanisms of toxicity, and
      imaging of bile salt transport inhibition in sandwich-cultured hepatocytes can be
      used to predict cholestasis-inducing compounds. Imaging of micronuclei formation
      in simple cell models can be used to detect genotoxic potential and elucidate
      anuegenic or clastogenic mode of actions. The hope is that application of these
      relatively predictive assays during drug discovery will reduce toxicity and
      safety-related attrition of drug development programmes at later stages. 

PMID- 24461079
TI  - A regulatory role for CD72 expression on B cells in systemic lupus erythematosus.
AB  - BACKGROUND: B regulatory cells and their regulatory products/markers, such us
      semaphorin 3A (sema3A) and its receptor NP-1, FcgammaIIB, IL-10, and others, act
      at the very base of self-tolerance, maintenance, and prevention of autoimmune
      disease development. OBJECTIVES: The aim of the present study was to assess the
      involvement of CD72, a regulatory receptor on B cells, in systemic lupus
      erythematosus (SLE). In addition, the potential of soluble sema3A in enhancing
      the expression of CD72 on B cells of SLE patients was investigated. RESULTS: CD72
      expression on activated B cells of SLE patients was significantly lower than that
      of normal controls. This lower expression of CD72 in SLE patients correlated
      inversely with SLE disease activity and was associated with lupus nephritis, the
      presence of anti-dsDNA antibodies, and low levels of complement. Co-culture of
      purified B cells from healthy controls with condition-media containing
      recombinant sema3A resulted in significant enhancement of CD72. Similar
      enhancement of CD72 on activated B cells from SLE patients, though significant,
      was still lower than in normal individuals. CONCLUSIONS: The lower expression of
      CD72 on activated B cells from SLE patients correlates with SLE disease activity,
      lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of
      complement. The improvement of CD72 expression following the addition of soluble
      semaphorin 3A suggests that CD72 may be useful as a biomarker to be followed
      during the treatment of SLE.

PMID- 24461078
TI  - "Generalized osteoarthritis": a systematic review.
AB  - OBJECTIVES: Given the conflicting definitions of "generalized osteoarthritis"
      (GOA) in the literature, we performed a systematic review of GOA definitions,
      risk factors, and outcomes. METHODS: We searched the MEDLINE literature with the
      terms osteoarthritis, generalized, polyarticular, multiple joint, and multi-joint
      to obtain articles related to GOA, following evidence-based guidelines. Titles
      and abstracts of 948 articles were reviewed, with full-text review of 108. Data
      were extracted based on pre-specified criteria for 74 articles plus 24 identified
      through bibliographic review (n = 98). RESULTS: Twenty-four large cohorts (n ~
      30,000) were represented along with numerous clinical series (n ~ 9000), across
      22 countries and 60 years (1952-2012). No less than 15 definitions of GOA were
      given in 30 studies with a stated GOA definition; at least 6 groups used a summed
      score of joints or radiographic grades. Prevalence estimates based on these GOA
      definitions were 1-80%, although most were 5-25%. Increased risk and progression
      of GOA was associated with age, female sex, and genetic/familial factors.
      Associations with increased body mass index or bone mineral density were not
      consistent. A study estimated the heritability of GOA at 42%. Collagen biomarker
      levels increased with the number of involved joints. Increased OA burden was
      associated with increased mortality and disability, poorer health, and function.
      CONCLUSION: While there remains no standard definition of GOA, this term is
      commonly used. The impact on health may be greater when OA is in more than one
      joint. A descriptive term, such as multi-joint or polyarticular OA, designating
      OA of multiple joints or joint groups is recommended.

PMID- 24461080
TI  - Characterisation of the cytokine milieu associated with the up-regulation of IL-6
      and suppressor of cytokine 3 in chronic hepatitis C treatment non-responders.
AB  - BACKGROUND & AIMS: In chronic hepatitis C virus infection (CHC), expression of
      suppressor of cytokine signalling-3 (SOCS3) has been shown to be associated with
      obesity and non-response to antiviral therapy. In this study, we aimed to
      determine the effect of SOCS3 induction on the cytokine response in patients
      receiving Pegylated interferon (PegIFN) and ribavirin (RBV) therapy. METHODS:
      Peripheral blood mononuclear cells (PBMC) collected at baseline and at 12 weeks
      from CHC patients receiving PegIFN/RBV therapy were examined for mRNA and protein
      SOCS3 expression. Immunological assays were employed to examine cytokine
      production. RESULTS: There was increased expression of SOCS3 in PBMC of non
      responders at week 12 of therapy, when compared to treatment responders (P =
      0.0001). The expression of SOCS3 correlated with body mass index (BMI) (r = 0.54;
      P = 0.01). Patients with low SOCS3 expression at week 12 of therapy had lower HCV
      specific IFN-gamma production in enzyme-linked immunosorbent spot (ELISpot)
      assays (P = 0.01), and reduced ex-vivo production of the anti-HCV effector
      cytokines interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha(P = 0.01 and
      P = 0.04 respectively). Analysis of serum cytokine levels revealed higher levels
      of IL-6 at week 12 in the high SOCS3 expression group (P = 0.02) while IL-6
      levels correlated with SOCS3 expression in the entire cohort (P = 0.04). Ex-vivo
      studies confirmed that IL-6 induced SOCS3, and neutralisation of IL-6 reduced
      levels of SOCS3. CONCLUSION: In subjects with increased BMI and non-response to
      antiviral therapy, the IL-6/SOCS3 axis appears to play a crucial role in altering
      the anti-HCV-cytokine response associated with antiviral therapy.

PMID- 24461081
TI  - Pathology of bladder cancer among diabetic patients undergoing radical cystectomy
      with a history of pioglitazone (Actos) use.
AB  - BACKGROUND: Prospective studies suggested an association between pioglitazone
      (Actos) use and the development of bladder cancer. Cancer pathology among
      pioglitazone users has not been characterized. We chose to compare the surgical
      pathology among diabetic users and non-users, as well as non-diabetic patients
      who underwent radical cystectomy for bladder cancer. METHODS: Our single-center,
      prospectively-maintained bladder cancer database was reviewed. Patient
      demographics, surgical pathology, and outcomes were evaluated. Information
      regarding diabetic history and use of pioglitazone was determined from chart
      analysis and patient interview. RESULTS: From April 2005 to October 2011, 204
      patients undergoing radical cystectomy were identified. Of these, 33 (16.2%) were
      diabetic and 171 (83.8%) had no history of diabetes. Among diabetic patients, 9
      (27.3%) had a history of pioglitazone use. Median duration of therapy was 14 (6
      120) months. Pathology in non-diabetic patients was T1 in 17 (9.9%), T2 in 38
      (22.2%), T3 in 44 (25.7%), and T4 in 31 (18.1%). Pathology among diabetic non
      users was T1 in 1 (4.2%), T2 in 7 (29.2%), T3 in 7 (29.2%), and T4 in 4 (16.7%).
      Pathologic stage among diabetic users was T1 in 1 (11.1%), T2 in 3 (33.3%), T3 in
      3 (33.3%), and T4 in 1 (11.1%). Lymph node involvement in non-diabetics, diabetic
      non-users, and diabetic users was 25.7%, 33.3%, and 33.3%, respectively. Cancer
      specific death was seen in 60.3% of non-diabetics, 58.3% of diabetic non-users,
      and 75% of diabetic users. CONCLUSIONS: Diabetics have similar stage distribution
      regardless of pioglitazone use. Lymph node metastases rates and cancer specific
      death were similar across all groups. Additional studies will serve to better
      characterize this relationship.

PMID- 24461083
TI  - Is the unconscious, if it exists, a superior decision maker?
AB  - Newell & Shanks (N&S) show that there is no convincing evidence that processes
      assumed to be unconscious and superior are indeed unconscious. We take their
      argument one step further by showing that there is also no convincing evidence
      that these processes are superior. We review alternative paradigms that may
      provide more convincing tests of the superiority of (presumed) unconscious
      processes. 

PMID- 24461082
TI  - Clinical features of drug abuse that reflect genetic risk.
AB  - BACKGROUND: Drug abuse (DA) is a clinically heterogeneous syndrome. Can we, in a
      large epidemiological sample, identify clinical features of DA cases that index
      genetic risk? METHOD: Using registration in medical, legal or pharmacy records,
      we identified four kinds of relative pairs (n=935,854) starting with a proband
      with DA: monozygotic co-twins; full siblings; half-siblings; and cousins. Using
      linear hazard regression, we examined the interaction between three clinical
      features of DA in the proband and risk for DA in these four relative pairs,
      ordered by degree of genetic relationship. RESULTS: Increased risk for DA in
      relatives was robustly predicted by early age at first registration, total number
      of registrations, and ascertainment in the criminal versus the medical or
      pharmacy registry. In multivariate models, all three of these variables remained
      significant and in aggregate strongly predicted DA risk in relatives. The risk
      for DA in siblings of DA probands in the highest decile of genetic risk predicted
      by our three indices was more than twice as great as that predicted in siblings
      of probands in the lowest decile of risk. CONCLUSIONS: In an epidemiological
      sample, genetic risk for DA can be substantially indexed by simple clinical and
      historical variables.

PMID- 24461084
TI  - Use of biomarkers in the context of orphan medicines designation in the European
      Union.
AB  - The use of biomarkers within the procedures of the Committee of Orphan Medicinal
      Products (COMP) of the European Medicines Agency (EMA) is discussed herein. The
      applications for Orphan Medicinal Product designation in the EU are evaluated at
      two stages. At the time of orphan designation application, the file undergoes an
      assessment to establish whether the proposed condition is a distinct and serious
      condition affecting not more than 5 in 10,000 people in the EU, and whether the
      product is plausible as a therapy for that condition. In cases where therapies
      already exist, the significant benefit of the candidate product over existing
      therapies is also evaluated. The orphan criteria are reassessed at the time of
      marketing authorisation, so that marketing exclusivity for the product in the
      orphan medical condition can be granted. Within this context, biomarkers have
      been used in submissions in order to define an orphan condition and to justify
      that the criteria for orphan designation are met. The current work discusses
      specific examples from the experience of the COMP, where biomarkers have played a
      decisive role. Importantly, it identifies the proposal of sub-sets of non-rare
      conditions based on biomarkers as a challenging issue in the evaluation of
      applications. In particular two specific requirements for the candidate orphan
      medicines in relation to the biomarker-based subsets are highlighted: the
      "plausible link to the condition" and the "exclusion of effects outside the
      subset". 

PMID- 24461085
TI  - Incidence and complications of peptic ulcer disease requiring hospitalisation
      have markedly decreased in Finland.
AB  - BACKGROUND: The characteristics of peptic ulcer disease (PUD) are changing. AIM:
      To evaluate time trends in the incidence of PUD and its complications in
      hospitalised patients at the beginning of the 21st century, drug therapies in out
      patient care as a risk factor for recurrent PUD, and medication used by PUD
      patients compared with the background population. METHODS: In this retrospective
      epidemiologic cohort study, data from the years 2000-2008 came from The Hospital
      District of Helsinki and Uusimaa, and the Finnish Care Register. All hospitalised
      adult patients with PUD in the capital region of Finland were included. The data
      were linked with nationwide Prescription Register of the Finnish Social Insurance
      Institution allowing detailed individual medicine purchase data. RESULTS: A total
      of 9951 peptic ulcers were detected among 8146 individual patients during the
      study period. The mean annual incidence of all peptic ulcers decreased from
      121/100,000 (95% CI: 117-125) in 2000-2002, to 79 (95% CI: 76-82) in 2006-2008
      [Incidence rate ratio = 0.62 (95% CI: 0.58-0.64), P < 0.001 after age and sex
      adjustment]. Decrease in incidence was seen in all age groups and in both sexes.
      The overall rate of severe complications of PUD was reduced. One-year cumulative
      incidence of recurrent ulcers was 13%. Use of several drugs was associated with
      increased risk for recurrence. The purchases of various drugs were more common
      among PUD patients compared with background population. CONCLUSIONS: Both the
      incidence and complication rates have markedly decreased during the study period.
      Recurrent peptic ulcer disease was associated with polypharmacy.

PMID- 24461086
TI  - [Opinions on incidents in interventional radiology].

PMID- 24461087
TI  - [Oral contraceptives, risks and hazards].

PMID- 24461088
TI  - [Early hypertrophic scar after surgery on the nasal region: value of long-acting
      corticosteroid injections].
AB  - BACKGROUND: "Pincushioning" is a complication of post-surgical scarring following
      use of transposition flaps particularly when surgery is performed on the nasal
      region. The transposition flap technique is very useful for the repair of certain
      defects of the tip of the nose, the medial canthus or of the ala nasi. The aim of
      this study is to define the clinical characteristics of this scarring dystrophy,
      which we propose to call "early hypertrophy scarring", to clarify the nature
      thereof and to assess the efficacy of intralesional injection of corticosteroids
      at the first signs of hypertrophy. PATIENTS AND METHOD: A prospective, open, non
      comparative, single-centre study examined the clinical and histological
      characteristics of early hypertrophy scarring and the effectiveness of therapy
      with one or two injections of corticosteroids performed on the 15th day post
      operatively and optionally repeated at D45 depending on the outcome. From January
      2011 to January 2013, 12 consecutive patients with early hypertrophy scarring
      were included (ten men and two women - mean age: 64 years). All had undergone
      surgery for basal cell carcinoma under local anaesthesia with one-stage repair by
      means of a rhombic flap or a bilobed flap located in the nasal area. Scars were
      injected strictly intra-lesionally with triamcinolone acetate (40 mg/1 mL) until
      whitening occurred. A single injection was performed in three cases of rhombic
      flap while a second injection was given at D45 in the remaining nine cases.
      RESULTS: Complete regression of the early hypertrophy scarring was obtained in
      ten of the 12 patients by D90. Incomplete regression was observed but with a
      marked improvement in the other two patients. DISCUSSION: Early hypertrophy
      scarring is distinguished by its clinical characteristics of hypertrophic or
      keloid scars. Biopsy performed in two cases showed the fibrous but non-fatty
      nature of early hypertrophy scarring. Biomechanical factors particular to the
      nasal region and the transposition flap technique could account for the early and
      excessive collagen production causing early hypertrophy scarring. Early injection
      of corticosteroids, which was consistently effective in our study, could
      represent a simple treatment for early hypertrophy scarring, thus avoiding
      surgical correction. These preliminary results in a small number of patients
      require confirmation by a comparative, multicentre, prospective controlled study.

PMID- 24461089
TI  - [Temporary localized alopecia following neuroradiological procedures: 18 cases].
AB  - BACKGROUND: The treatment of cerebral lesions using endovascular radiological
      procedures is becoming a standard of care. Radiation-induced alopecia, a type of
      acute radiodermatitis, is a frequent complication. Between 2009 and 2010, a
      number of patients reported hair loss after embolization of a cerebral
      arteriovenous malformation at the Neuroradiology Department of the Strasbourg
      University Hospital. We therefore retrospectively investigated 18 cases to better
      delineate the circumstances and the risk factors associated with radiation
      induced alopecia. PATIENTS AND METHODS: We reviewed the records of 35 patients
      reporting hair loss among the 347 patients undergoing embolization of cerebral
      arteriovenous malformations between January 2008 and May 2010. Only patients with
      photographically documented complete circumscribed alopecia were included.
      Patients were examined and interviewed by a dermatologist and/or a radiologist at
      the time of hair loss and at a later point. The cumulative dose of radiation
      delivered to the skin in the 3 months preceding onset of alopecia, then over the
      entire period 2008-2010, was calculated. These doses included the diagnostic
      (angiography) and therapeutic (embolization) procedures. RESULTS: Definite
      circumscribed alopecia was noted in 18 patients. Alopecia occurred between two
      and four weeks after embolization; it was complete and in no cases cicatricial.
      Complete recovery as attested by examination or photography was observed in 12
      patients. The cumulative dose over the preceding three months was between 2.5 Gy
      and 12.3 Gy (mean: 5 Gy). The total cumulative dose since January 2008 was
      between 3.2 and 17 Gy (mean: 7 Gy). DISCUSSION: We describe a series of 18
      patients with radio-induced alopecia occurring after diagnostic and therapeutic
      procedures for cerebral arteriovenous malformations. This series is particularly
      interesting because it includes the largest patient sample reported to date with
      an uncommon large area of alopecia, and also because we were able to calculate
      the cumulative dose of radiation delivered to the skin. In addition, we underline
      the importance of the cumulative dose in interventional radiology since radio
      induced alopecia probably results from the number of interventional procedures
      during a given time period. Moreover, analysis of these doses provided us with a
      new perspective on the radiobiology of the hair growth cycle. Indeed, whereas
      previously reported data considered alopecia as definitive where doses higher
      than 7 Gy were delivered, we noticed regrowth of hair with doses of up to 12 Gy.
      CONCLUSION: These observations underline the specific findings of radiation
      induced alopecia and underline the importance of the cumulative radiation dose
      delivered during the 3 months preceding alopecia.

PMID- 24461090
TI  - [A study of 19 cases of allergy to heparins with positive skin testing].
AB  - BACKGROUND: Allergic hypersensitivity to unfractioned or low-molecular-weight
      heparins is uncommon but is known, and in particular the most common form is
      localized dermatitis, although such cases have seldom turned into maculopapular
      exanthema. Since cross-reactions with other heparins are frequent, identification
      of therapeutic alternatives is essential. PATIENTS AND METHODS: This
      retrospective study included patients referred to the Department of Dermatology
      and Allergology at Tenon Hospital between 2000 and 2012 with suspicion of allergy
      to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and
      sensitized to at least one heparin (i.e. positive skin tests to at least one
      heparin). The heparins and hirudins used were tested in the forearm by means of
      intradermal skin tests. All patients were contacted in 2012 to establish whether
      they had used some form of heparin since the cutaneous allergy tests. RESULTS:
      Nineteen patients had at least one positive skin test for heparin; 1 patient had
      presented anaphylactic shock, while 18 others had presented localized eczema (12)
      or generalized dermatitis (6). The heparin most often responsible for these
      adverse reactions was enoxaparin (13/19). An LMWH was responsible in most cases
      (18 vs. 1 with UFH). Of these 18 patients, 16 also presented positive skin tests
      for UFH, 9 for synthetic heparinoid and 1 for hirudin. 11/19 patients were tested
      for fondaparinux (a synthetic pentasaccharid) and all had negative skin tests.
      5/7 patients with negative skin tests had taken fondaparinux without any visible
      reaction, whereas 2 who also tested negative experienced localized eruption at
      the injection site. DISCUSSION: Our results underline the greater frequency of
      delayed hypersensitivity reactions compared with immediate reactions to heparins.
      Skin tests can help to identify substitution molecules. Fondaparinux might be an
      alternative but certain diagnosis relies on rechallenge.

PMID- 24461091
TI  - [Mastitis revealing Churg-Strauss syndrome].
AB  - BACKGROUND: Churg-Strauss syndrome often involves the skin, and this may
      sometimes reveal the disease. OBSERVATION: A 25-year-old woman was referred to a
      gynaecologist for inflammation of the right breast with breast discharge.
      Cytological analysis of the liquid showed numerous inflammatory cells,
      particularly polymorphonuclear eosinophils and neutrophils. Ultrasound
      examination of the breast was consistent with galactophoritis. CRP was normal,
      and hypereosinophilia was seen. The patient was subsequently referred to a
      dermatology unit. Skin examination revealed inflammation of the entire breast,
      which was painful, warm and erythematous; the border was oedematous with
      blisters. Necrotic lesions were also present on the thumbs and knees. Skin biopsy
      of the breast showed a dermal infiltrate with abundant infiltrate of
      polymorphonuclear eosinophils, including patchy necrosis and intraepidermal
      vesicles. Histological examination of a biopsy sample from a thumb revealed
      eosinophilic granuloma and leukocytoclastic vasculitis. The patient was also
      presenting asthma, pulmonary infiltrates and mononeuropathy at L3, consistent
      with Churg-Strauss syndrome. DISCUSSION: Breast involvement in Churg-Strauss
      syndrome is very rare (only one other case has been reported). This is the first
      case in which the breast condition revealed the disease. Cutaneous involvement of
      the breast is, however, also compatible with Wells' cellulitis. The lesions
      quickly disappeared with 1mg/kg/d oral prednisolone.

PMID- 24461093
TI  - [Palmoplantar keratoderma: a rare manifestation of myxoedema].
AB  - BACKGROUND: Herein we report a rare case of acquired palmoplantar keratoderma in
      association with myxoedema and hypothyroidism. PATIENTS AND METHODS: A 53-year
      old woman presented with palmoplantar keratoderma, dry skin, muscular weakness
      and cramps for 9 months. The laboratory work-up revealed autoimmune thyroiditis
      with hypothyroidism. Skin biopsy showed chronic eczema. Other causes of acquired
      palmoplantar keratoderma were ruled out. Rapid improvement was achieved within 3
      weeks of institution of hormone replacement therapy. DISCUSSION: Although this
      association is very rare, hypothyroidism must be suspected in patients with
      acquired palmoplantar keratoderma, particularly when it occurs in association
      with systemic symptoms.

PMID- 24461092
TI  - [Recurrent pyoderma gangrenosum-like ulcers induced by oral anticoagulants].
AB  - BACKGROUND: Other than the classic skin necrosis induced by oral anticoagulants
      (OAC) in patients with protein C and S deficiencies, other types of OAC induced
      skin ulcers are little known. Herein, we describe an original case of recurrent
      pyoderma gangrenosum (PG)-like ulcers induced by OAC. PATIENTS AND METHODS: A 70
      year-old female heart-transplant recipient presented deep, hyperalgesic and
      quickly-spreading necrotic ulceration of the right leg 6 weeks after starting
      oral anticoagulant therapy with fluindione. Histological analysis revealed dermal
      infiltrate containing polynuclear neutrophils, which accords with the
      histopathological diagnosis of leukocytoclastic vasculitis or PG. Infectious,
      autoimmune and thrombophilic causes were ruled out. Fluindione was withdrawn and
      the ulcer healed completely within a month. Six months later, right leg
      ulceration recurred two weeks after the patient resumed fluindione but healed
      within 1 month of discontinuation of the drug. An OAC from another chemical
      family (warfarin) was then introduced, with further recurrence of ulceration
      after 2 weeks of treatment. DISCUSSION: The chronology of events and the
      negativity of aetiological explorations allowed a diagnosis to be made of OAC
      induced skin ulcer, a rare complication of which the pathophysiology is unclear.
      This is the first case of PG-like ulcers induced by OAC.

PMID- 24461094
TI  - [Blastic plasmacytoid dendritic cell neoplasm revealed by ecchymotic lesions on
      the face].
AB  - BACKGROUND: Cutaneous CD4+CD56+ malignant tumor proliferation was previously
      called "CD4/CD56 hematodermic neoplasm". However, the most recent studies have
      shown that the disease develops from plasmacytoid dendritic cells and the tumor
      has been renamed "Blastic Plasmacytoid Dendritic Cell Neoplasm" (BPDCN). It is an
      aggressive disease with a poor prognosis and behaves like acute leukemia in the
      short to moderate term. PATIENTS AND METHODS: A 65-year-old man with no
      particular history consulted for a left laterocervical lesion of ecchymotic
      aspect that had appeared one year earlier. Topical corticosteroid therapy had
      been unsuccessful. Examination of biopsies with lymphocyte typing enabled a
      diagnosis of BPDCN to be made. At the histopathological level, biopsy showed an
      infiltrate comprising medium to large cells. Immunohistochemical examination was
      remarkable for the absence of expression of markers of T- and B-cell lines.
      However, these tumor cells expressed CD4, CD56 and TCL1. Staging of the disease
      was normal. Treatment with chemotherapy was initiated in collaboration with a
      team of hematologists. Autologous bone marrow transplant was then performed.
      DISCUSSION: BPDCN is a rare malignant blood dyscrasia. It is distinguished by
      inaugural skin involvement, with systemic manifestations occurring much later.
      Histopathological examination of a skin biopsy with immunostaining establishes
      the diagnosis. In terms of phenotype, the tumor population is highly
      characteristic. The cells are negative for antigens of T- and B- cell lines.
      However, these cells express CD4, CD56 and TCL1, which are markers of
      plasmacytoid dendritic cells. The disease carries a poor prognosis and evolves in
      the short to middle term in the same way as acute leukemia. First-line treatment
      consists of the chemotherapy regimens used in aggressive lymphoma or acute
      leukemia. A bone marrow graft is sometimes performed at the time of initial
      relapse. Average survival is 12 months for chemotherapy alone and 30 months for
      transplant after first relapse. Early bone marrow transplantation has been shown
      to improve survival.

PMID- 24461095
TI  - [Hyperpigmentation of the forehead after baptism: a phototoxic reaction due to
      chrism].

PMID- 24461096
TI  - [The place of skin substitutes in surgical treatment of necrotising cellulitis:
      seven cases].

PMID- 24461097
TI  - [Disseminated superficial porokeratosis in a black woman].

PMID- 24461098
TI  - [Non-syndromic cutaneous vascular malformations].

PMID- 24461099
TI  - [Subungual melanoma].

PMID- 24461100
TI  - [Solar lentigo diagnosed by reflectance confocal microscopy].

PMID- 24461101
TI  - [BB creams: a revolutionary product dating from...1860].

PMID- 24461102
TI  - [Hereditary pigmentary disorders: light from the East].

PMID- 24461103
TI  - [Onychomatricoma].

PMID- 24461104
TI  - [Subungual verrucous carcinoma].

PMID- 24461105
TI  - [Nail psoriasis and silver: a magic ring...].

PMID- 24461106
TI  - [Unintended changes in the composition of a drug commonly used in dermatology
      caused by its container].

PMID- 24461107
TI  - CT-based three-dimensional kinematic comparison of dart-throwing motion between
      wrists with malunited distal radius and contralateral normal wrists.
AB  - AIM: To compare motion of the capitate, scaphoid, and lunate in wrists with a
      malunited distal radius and contralateral normal wrists during dart-throwing
      motion (DTM) by three-dimensional kinematic studies using computed tomography
      (CT) images. MATERIALS AND METHODS: CT was performed simultaneously on both
      wrists in six patients with a unilateral distal radius malunion at three stepwise
      positions simulating DTM. Using volume registration technique, the kinematic
      variables of helical axis motion of the capitate, scaphoid, and lunate were
      calculated and compared between both wrists. The helical motion of the capitate
      was also evaluated in a scaphoid- and lunate-based coordinate system. RESULTS:
      Among the average rotation and translation of the scaphoid, lunate, and capitate
      during DTM, only the average rotation of the capitate was significantly different
      between the uninjured (88.9 degrees ) and the injured (70 degrees ) wrist (p =
      0.0075). Rotation of the capitate relative to the scaphoid (26.3 degrees  versus
      37.8 degrees , p = 0.029) or lunate (39.2 degrees  versus 59.3 degrees , p =
      0.028) was smaller in the malunited wrist. The centres of helical axis motion of
      the three carpal bones were located more dorsally and radially in the injured
      wrist. CONCLUSIONS: The present study showed that decreased DTM in wrists with a
      distal radius malunion resulted from decreased midcarpal motion. The present
      study of the capitate, scaphoid, and lunate in wrists with distal radius malunion
      might be the first to present a 3D kinematic analysis of the effect of distal
      radius malunion on the carpal bones.

PMID- 24461108
TI  - Validation of the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4,
      a simplified severity scale for assessing skin lesions of atopic dermatitis in
      dogs.
AB  - BACKGROUND: Severity scales are used to grade skin lesions in clinical trials for
      treatment of dogs with atopic dermatitis (AD). At this time, only two scales have
      been validated, namely the Canine Atopic Dermatitis Extent and Severity Index
      (CADESI)-3 and the Canine Atopic Dermatitis Lesion Index (CADLI). However, the
      high number of assessed sites makes the CADESI-3 impractical.
      HYPOTHESIS/OBJECTIVES: The aim of this study was to develop and validate a fourth
      version of the CADESI that is simpler and quicker to administer. METHODS: Body
      sites, lesions and severity grades were revised by members of the International
      Committee on Allergic Diseases of Animals (ICADA). The newly designed CADESI-4
      was tested for its validity (i.e. content, construct and criterion), reliability
      (i.e. inter- and intra-observer reliability and internal consistency),
      responsiveness (i.e. sensitivity to change) and time to administer. Disease
      severity benchmarks were chosen using receiver operating characteristic
      methodology. RESULTS: The CADESI-4 was simplified in comparison to its previous
      version to comprise 20 body sites typically affected in atopic dogs. Three
      lesions (erythema, lichenification and alopecia/excoriation) were scored from 0
      to 3 at each site. The CADESI-4 had satisfactory validity, reliability and
      sensitivity to change. On average, the time to administer a CADESI-4 was one
      third that of a CADESI-3. Proposed benchmarks for mild, moderate and severe AD
      skin lesions are 10, 35 and 60, respectively. CONCLUSIONS AND CLINICAL
      IMPORTANCE: The CADESI-4 is simpler to use and quicker to administer than its
      previous version. The ICADA recommends the CADESI-4 instead of the CADESI-3 to
      score skin lesions of AD in dogs enrolled in clinical trials.

PMID- 24461109
TI  - Management of hyperglycemia associated with pasireotide (SOM230): healthy
      volunteer study.
AB  - AIMS: Pasireotide, a multireceptor-targeted somatostatin analogue with efficacy
      in Cushing's disease and acromegaly, can affect glucose metabolism due to
      inhibition of insulin secretion and incretin hormone responses. A study was
      therefore conducted to evaluate different antihyperglycemic drugs in the
      management of pasireotide-associated hyperglycemia. METHODS: This was a 1-week,
      Phase I, open-label study. Healthy male volunteers were randomized to pasireotide
      600 MUg sc bid alone or co-administered with metformin 500 mg po bid, nateglinide
      60 mg po tid, vildagliptin 50mg po bid, or liraglutide 0.6 mg sc qd. An oral
      glucose tolerance test (OGTT) was performed on days 1 and 7 to evaluate effects
      on serum insulin, plasma glucose and glucagon levels. Safety/tolerability and
      pharmacokinetic effects were also evaluated. RESULTS: Ninety healthy male
      volunteers were enrolled (n=18 per arm). After 7 days of treatment, plasma
      glucose AUC post-OGTT increased by 69% with pasireotide alone. The effect was
      reduced by 13%, 29%, 45% and 72% with co-administration of metformin,
      nateglinide, vildagliptin and liraglutide, respectively. On day 7, compared with
      pasireotide alone, the decrease in serum insulin was attenuated with nateglinide,
      metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%,
      34% and 71% higher, respectively). Minimal changes in plasma glucagon were
      observed. Adverse events were consistent with the safety profiles of the drugs
      used. CONCLUSIONS: Vildagliptin and liraglutide were most effective in minimizing
      pasireotide-associated hyperglycemia in healthy volunteers.

PMID- 24461110
TI  - Only just the beginning of the end of hepatitis C.

PMID- 24461111
TI  - Gout: a disease of the past, the present, but not the future?

PMID- 24461112
TI  - Support for LGBTQ youth.

PMID- 24461114
TI  - Field hospitals in Syria.

PMID- 24461115
TI  - Field hospitals in Syria.

PMID- 24461116
TI  - Research on hormonal contraception and HIV.

PMID- 24461117
TI  - Research on hormonal contraception and HIV.

PMID- 24461118
TI  - Research on hormonal contraception and HIV.

PMID- 24461119
TI  - Research on hormonal contraception and HIV - Authors' reply.

PMID- 24461120
TI  - Linagliptin for elderly patients with type 2 diabetes.

PMID- 24461121
TI  - Linagliptin for elderly patients with type 2 diabetes.

PMID- 24461122
TI  - Linagliptin for elderly patients with type 2 diabetes.

PMID- 24461123
TI  - Linagliptin for elderly patients with type 2 diabetes - Authors' reply.

PMID- 24461124
TI  - Cryoglobulinaemia identified by repeated analytical failure of laboratory tests.

PMID- 24461125
TI  - The changing landscape of radiology: ultrasound training for nonradiologists.

PMID- 24461126
TI  - Estimation of standardized hospital costs from Medicare claims that reflect
      resource requirements for care: impact for cohort studies linked to Medicare
      claims.
AB  - OBJECTIVE: To compare cost estimates for hospital stays calculated using
      diagnosis-related group (DRG) weights to actual Medicare payments. DATA
      SOURCES/STUDY SETTING: Medicare MedPAR files and DRG tables linked to participant
      data from the Study of Osteoporotic Fractures (SOF) from 1992 through 2010.
      Participants were women age 65 and older recruited in three metropolitan and one
      rural area of the United States. STUDY DESIGN: Costs were estimated using DRG
      payment weights for 1,397 hospital stays for 795 SOF participants for 1 year
      following a hip fracture. Medicare cost estimates included Medicare and secondary
      insurer payments, and copay and deductible amounts. PRINCIPAL FINDINGS: The mean
      (SD) of inpatient DRG-based cost estimates per person-year were $16,268 ($10,058)
      compared with $19,937 ($15,531) for MedPAR payments. The correlation between DRG
      based estimates and MedPAR payments was 0.71, and 51 percent of hospital stays
      were in different quintiles when costs were calculated based on DRG weights
      compared with MedPAR payments. CONCLUSIONS: DRG-based cost estimates of hospital
      stays differ significantly from Medicare payments, which are adjusted by Medicare
      for facility and local geographic characteristics. DRG-based cost estimates may
      be preferable for analyses when facility and local geographic variation could
      bias assessment of associations between patient characteristics and costs.

PMID- 24461127
TI  - Surface chemistry of SnO2 nanowires on Ag-catalyst-covered Si substrate studied
      using XPS and TDS methods.
AB  - In this paper we investigate the surface chemistry, including surface
      contaminations, of SnO2 nanowires deposited on Ag-covered Si substrate by vapor
      phase deposition (VPD), thanks to x-ray photoelectron spectroscopy (XPS) in
      combination with thermal desorption spectroscopy (TDS). Air-exposed SnO2
      nanowires are slightly non-stoichiometric, and a huge amount of C contaminations
      is observed at their surface. After the thermal physical desorption (TPD)
      process, SnO2 nanowires become almost stoichiometric without any surface C
      contaminations. This is probably related to the fact that C contaminations, as
      well as residual gases from air, are weakly bounded to the crystalline SnO2
      nanowires and can be easily removed from their surface. The obtained results gave
      us insight on the interpretation of the aging effect of SnO2 nanowires that is of
      great importance for their potential application in the development of novel
      chemical nanosensor devices. 

PMID- 24461129
TI  - JVIR Mille Bornes: A record number of submissions.

PMID- 24461128
TI  - Bosutinib inhibits migration and invasion via ACK1 in KRAS mutant non-small cell
      lung cancer.
AB  - The advent of effective targeted therapeutics has led to increasing emphasis on
      precise biomarkers for accurate patient stratification. Here, we describe the
      role of ACK1, a non-receptor tyrosine kinase in abrogating migration and invasion
      in KRAS mutant lung adenocarcinoma. Bosutinib, which inhibits ACK1 at 2.7 nM
      IC50, was found to inhibit cell migration and invasion but not viability in a
      panel of non-small cell lung cancer (NSCLC) cell lines. Knockdown of ACK1
      abrogated bosutinib-induced inhibition of cell migration and invasion
      specifically in KRAS mutant cells. This finding was further confirmed in an in
      vivo zebrafish metastatic model. Tissue microarray data on 210 Singaporean lung
      adenocarcinomas indicate that cytoplasmic ACK1 was significantly over-expressed
      relative to paired adjacent non-tumor tissue. Interestingly, ACK1 expression in
      "normal" tissue adjacent to tumour, but not tumour, was independently associated
      with poor overall and relapse-free survival. In conclusion, inhibition of ACK1
      with bosutinib attenuates migration and invasion in the context of KRAS mutant
      NSCLC and may fulfil a therapeutic niche through combinatorial treatment
      approaches. 

PMID- 24461130
TI  - Ethanol embolotherapy of vascular malformations: clinical outcomes at a single
      center.
AB  - PURPOSE: To retrospectively evaluate the results of endovascular therapy of
      vascular malformations principally treated with ethanol embolization at a single
      center. MATERIALS AND METHODS: From May 1999 to December 2012, 46 patients (28
      female, 18 male) with vascular malformations (31 venous malformations, 15
      arteriovenous malformations [AVMs]) throughout the body (nine upper extremity, 31
      lower extremity, and six truncal) who underwent ethanol embolization were studied
      and followed up. Demographic factors, clinical findings, imaging data, and
      patient-reported changes in symptoms were collected and analyzed. Follow-up data
      were obtained by office visits, repeat imaging, and telephone contact. RESULTS:
      Twenty-four patients (52.2%) were considered cured, 12 (26.1%) showed
      improvement, and 10 (21.7%) had no change or showed worsening. Similar rates of
      cure or improvement were seen for AVMs and venous malformations (P = 0.67).
      Lesion location, depth, and size were not associated with differences in outcomes
      (P = .87, P = .37, and P = .61, respectively). Type 1 and type 2 AVMs were cured
      more often than other AVM types. The overall complication rate was 24% (11 of 46
      patients). Minor complications were seen in six individuals (13%), and major
      complications developed in five patients (11%). CONCLUSIONS: Ethanol embolization
      of vascular malformations produces good outcomes, with control or relief of
      symptoms in a majority of patients.

PMID- 24461131
TI  - Modified response evaluation criteria in solid tumors and European Association
      for The Study of the Liver criteria using delayed-phase imaging at an early time
      point predict survival in patients with unresectable intrahepatic
      cholangiocarcinoma following yttrium-90 radioembolization.
AB  - PURPOSE: To investigate early imaging prognostic factors in unresectable
      intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after
      yttrium-90 ((90)Y) radioembolization therapy. MATERIALS AND METHODS: In an
      institutional review board-approved prospective correlative study, 21 consecutive
      patients with ICC refractory to standard chemotherapy underwent (90)Y
      radioembolization therapy. Target and overall Response Evaluation Criteria In
      Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for
      the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and
      EASL criteria were modified for application on delayed phases of dynamic contrast
      enhanced cross-sectional imaging studies. Conventional definitions for complete
      and partial response were applied; these responses comprised objective response.
      Restaging imaging was obtained at 1- and 3-month intervals until patient death.
      Survival analyses by Kaplan-Meier and log-rank proportional models including
      application of the landmark method to avoid lead-time bias were performed from
      the day of treatment. Significance was set at P < .05. RESULTS: Median overall
      survival (OS) from the time of (90)Y therapy was 16.3 months (95% confidence
      interval, 7.2-25.4 mo). Significant differences between mRECIST and EASL versus
      RECIST were found when categorizing patients into responders and nonresponders (P
      < .001). Significantly prolonged OS was observed for patients with targeted
      objective response based on modified mRECIST and EASL criteria (P = .005 and P =
      .001, respectively) at 3 months. RECIST was not found to correlate with survival
      at 1- or 3-month follow-up. CONCLUSIONS: Modified target mRECIST and EASL
      criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y
      radioembolization therapy for ICC predicted OS. RECIST did not correlate with
      survival.

PMID- 24461132
TI  - Intraprocedural yttrium-90 positron emission tomography/CT for treatment
      optimization of yttrium-90 radioembolization.
AB  - Radioembolization with yttrium-90 ((90)Y) microspheres relies on delivery of
      appropriate treatment activity to ensure patient safety and optimize treatment
      efficacy. We report a case in which (90)Y positron emission tomography
      (PET)/computed tomography (CT) was performed to optimize treatment planning
      during a same-day, three-part treatment session. This treatment consisted of (i)
      an initial (90)Y infusion with a dosage determined using an empiric treatment
      planning model, (ii) quantitative (90)Y PET/CT imaging, and (iii) a secondary
      infusion with treatment planning based on quantitative imaging data with the goal
      of delivering a specific total tumor absorbed dose. 

PMID- 24461133
TI  - A simple method for estimating dose delivered to hepatocellular carcinoma after
      yttrium-90 glass-based radioembolization therapy: preliminary results of a proof
      of concept study.
AB  - PURPOSE: To investigate a simple semiquantitative method to estimate yttrium-90
      ((90)Y) dose delivered with radioembolization to infiltrative hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: In a prospective study, patients with
      infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based (90)Y
      radioembolization including technetium-99m macroaggregated albumin ((99m)Tc-MAA)
      hepatopulmonary shunt study before therapy and bremsstrahlung single photon
      emission computed tomography (SPECT)/computed tomography (CT) after (90)Y
      radioembolization. Baseline magnetic resonance imaging was coregistered with
      (99m)Tc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity
      ((90)Y radioactivity delivered to each cubic centimeter of tumor) was estimated
      based on a lobar infusion approach. Correlation between proportions of (99m)Tc
      MAA and (90)Y delivered to the tumor was investigated. Survival analysis was
      performed using Kaplan-Meier estimations. RESULTS: (90)Y therapy was administered
      in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm(3)).
      Higher intratumoral (90)Y dose predicted prolonged survival, with 13.2-month
      median survival in patients with HCC and mean (90)Y dose of >= 100 Gy versus 4.6
      month median survival for other patients (P < .001). Of administered (90)Y dose,
      51.9% was delivered to the targeted tumors compared with 74.1% of (99m)Tc-MAA
      with linear correlation between biodistribution of (99m)Tc-MAA and (90)Y observed
      (Pearson r = 0.774, P < .001). CONCLUSIONS: The findings in this study suggest
      that approximately 50% of administered (90)Y dose is taken up by targeted
      infiltrative HCC with PVT. Intratumoral (90)Y dose >= 100 Gy in unresectable
      infiltrative HCC via a lobar intraarterial approach is a positive prognostic
      factor for survival.

PMID- 24461134
TI  - Vertebroplasty trials: the medium is the message.

PMID- 24461135
TI  - Lost in translation? Error in review article in October JVIR.

PMID- 24461136
TI  - Authors response to letter to the editor re: "Surgical or endovascular therapy of
      abdominal penetrating ulcers and their natural history: a systematic review".

PMID- 24461137
TI  - Tissue expression and serum levels of periostin during pregnancy: a new biomarker
      of embryo-endometrial cross talk at implantation.
AB  - OBJECTIVE: The molecular aspects involved in human implantation include many
      elements that were first discovered due to their role in cancer cell metastasis.
      Periostin, a cell adhesion protein that allows the maintenance of cancer stem
      cells, may influence implantation. The objective of this experimental case
      control study was to investigate tissue and serum expression of periostin during
      pregnancy, and evaluate the potential role of periostin in endometrial
      receptivity and embryo implantation. STUDY DESIGN: Forty-five subjects were
      included in the final analysis: 15 women who had experienced spontaneous
      pregnancy loss were enrolled as cases, and 30 healthy pregnant women awaiting
      voluntary pregnancy termination were enrolled as controls. For both cases and
      controls, trophoblastic and decidual tissues were collected at 12 weeks of
      gestation. Periostin expression in decidual and trophoblastic tissues was
      evaluated by immunohistochemical staining and reverse transcription polymerase
      chain reaction in cases and controls, and periostin serum levels was analyzed by
      Western blotting assays in cases, controls and non-pregnant female volunteers.
      RESULTS: Periostin mRNA and protein levels were higher in decidual and
      trophoblastic tissues from women undergoing voluntary pregnancy termination
      compared with women who had experienced spontaneous pregnancy loss. This finding
      was also reflected at serum level. CONCLUSIONS: Periostin may be a serum marker
      of good endometrial receptivity and embryo quality, and predictive of pregnancy
      evolution.

PMID- 24461138
TI  - Bladder-neck effective, integrative pelvic floor rehabilitation program: follow
      up investigation.
AB  - OBJECTIVES: To evaluate the effectiveness of a pelvic floor rehabilitation
      program consisting of pelvic floor (PF) and transverse abdominal muscle (TrA) pre
      contraction, coordination training and sustained submaximal contractions
      employing a validated pelvic floor questionnaire. STUDY DESIGN: Fifty-five
      consecutive women with stress urinary incontinence (n=9), overactive bladder
      (n=9) or mixed symptoms (n=37) were invited to participate. The German version of
      the Australian pelvic floor questionnaire was completed by all women before and
      after treatment, and additional validated improvement and satisfaction scales
      assessed patient-centered outcome. Individual treatment programs were selected
      according to the dysfunction evaluated by vaginal palpation and perineal
      ultrasound. Bladder-neck effective pelvic floor contraction was ensured using
      perineal ultrasound. Co-contraction of TrA was incorporated. Active integration
      of the pelvic floor contraction into daily life and individual incontinence
      triggering activities was practiced (duration, submaximal contraction,
      maintenance, pre-contraction before breathing, getting up and urgency). RESULTS:
      Of 46 women with stress urinary incontinence symptoms, 67% and of 46 women with
      OAB symptoms 78% were improved or cured. Bladder, bowel and sexual function
      domain scales improved significantly after 1-6 sessions (median 2). Pre
      contraction of PF and TrA was routinely performed by 39 of 55 women (71%)
      resulting in less incontinence. CONCLUSION: The bladder-neck effective,
      integrative pelvic floor rehabilitation program is highly effective for SUI and
      OAB. Although PF strengthening with maximal contractions was omitted, these
      results are comparable with strength programs in the literature. Due to the
      integration of submaximal PF contractions into daily life and individual
      incontinence situations, life-long strength training might be unnecessary, and
      this has to be studied further.

PMID- 24461139
TI  - Rate of re-interventions after transvaginal pelvic organ prolapse repair using
      partially absorbable mesh: 20 months median follow-up outcomes.
AB  - OBJECTIVE: To report our experience regarding the use of partially absorbable
      mesh, evaluating the nature and rate of re-intervention after transvaginal pelvic
      organ prolapse repair. MATERIALS AND METHODS: We retrospectively collected data
      on 269 consecutive patients who underwent partially absorbable mesh repair
      between January 2009 and January 2011. Data were obtained from our hospital
      medical records and we phoned patients to check if they had surgery in another
      hospital since then. RESULTS: 250 patients were included, with a median follow-up
      duration of 20 months (range 8-34 months). The global rate of re-interventions
      was 8%. The main indications were mesh exposure (2%), prolapse recurrence (1.2%),
      and urinary complications such as de novo stress urinary incontinence (4.8%).
      Afterwards, we compared these data with those previously obtained in our centre
      with non-absorbable mesh. CONCLUSION: Our study shows that the use of a partially
      absorbable mesh is efficient and reliable with relatively low rates of re
      intervention. According to the available literature data, a partially absorbable
      mesh does not seem to give advantages in comparison with classic non-absorbable
      mesh regarding rates of re-intervention.

PMID- 24461140
TI  - The learning curve for hip arthroscopy: a systematic review.
AB  - PURPOSE: The learning curve for hip arthroscopy is consistently characterized as
      "steep." The purpose of this systematic review was to (1) identify the various
      learning curves reported in the literature, (2) examine the evidence supporting
      these curves, and (3) determine whether this evidence supports an accepted number
      of cases needed to achieve proficiency. METHODS: The electronic databases Embase
      and Medline were screened for any clinical studies reporting learning curves in
      hip arthroscopy. Two reviewers conducted a full-text review of eligible studies
      and a hand search of conference proceedings and reference sections of the
      included articles. Inclusion/exclusion criteria were applied, and a quality
      assessment was completed for each included article. Descriptive statistics were
      compiled. RESULTS: We identified 6 studies with a total of 1,063 patients.
      Studies grouped surgical cases into "early" versus "late" in a surgeon's
      experience, with 30 cases being the most common cutoff used. Most of these
      studies used descriptive statistics and operative time and complication rates as
      measures of competence. Five of 6 studies showed improvement in these measures
      between early and late experience, but only one study proposed a bona fide curve.
      CONCLUSIONS: This review shows that when 30 cases was used as the cutoff point to
      differentiate between early and late cases in a surgeon's experience, there were
      significant reductions in operative time and complication rates. However, there
      was insufficient evidence to quantify the learning curve and validate 30, or any
      number of cases, as the point at which the learning curve plateaus. As a result,
      this number should be interpreted with caution. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level IV studies.

PMID- 24461141
TI  - The prevalence of hip labral and chondral lesions identified by method of
      detection during periacetabular osteotomy: arthroscopy versus arthrotomy.
AB  - PURPOSE: Periacetabular osteotomy (PAO) has become an accepted treatment option
      for patients with severe hip dysplasia. In addition to correcting acetabular
      architecture, consideration has been given to concomitant joint evaluation and
      treatment of coexisting intra-articular pathologic conditions, which can be
      identified with hip arthroscopy or through an open arthrotomy. The purpose of
      this systematic review was to evaluate the prevalence of intra-articular
      pathologic conditions identified arthroscopically compared with that of those
      identified with open arthrotomy. METHODS: A systematic review of the literature
      was performed by a search of PubMed using the words "periacetabular osteotomy,"
      "Bernese osteotomy," and "Ganz osteotomy." Two reviewers searched for relevant
      articles that met established inclusion criteria, which follow: (1) they were in
      the English language, (2) they contained data on patients who underwent
      periacetabular osteotomy, (3) the study patients underwent concomitant
      arthroscopy or arthrotomy, and (4) the studies contained data on the intra
      articular findings at the time of osteotomy. Exclusion criteria included review
      articles, technique articles, articles reporting on the same patient population,
      and articles without reported patient data. RESULTS: After review of 361
      references and abstracts, 8 articles met the inclusion criteria. A total of 775
      patients who had undergone PAO were included in the 8 articles. Three articles
      inspected all joints at the time of PAO and accounted for 345 PAOs. Arthrotomy
      was used to evaluate 151 hips, and 31 (21%) labral tears were identified.
      Arthroscopy was used to evaluate 194 hips, and 162 (84%) labral tears were
      identified. The difference in prevalence is statistically significant (P < .05).
      Two of the 3 articles reported chondral injury: 141 (73%) acetabular chondral
      injuries and 52 (27%) femoral chondral injuries were noted in 194 hips.
      CONCLUSIONS: The prevalence of intra-articular damage, including labral injuries
      and pathologic conditions of cartilage, at the time of PAO is substantial. Labral
      tears and chondral injury appear to be better recognized with concomitant
      arthroscopy when compared with arthrotomy at the time of PAO. Further study is
      needed to determine whether the treatment of chondrolabral injuries can improve
      patient outcome and reduce reoperations. LEVEL OF EVIDENCE: Level IV, systematic
      review of Level IV studies.

PMID- 24461142
TI  - EU LIFE Programme: contributing to waste management in Europe for over 20 years.

PMID- 24461143
TI  - CHADS2, CHA2DS2-VASc and HAS-BLED as predictors of outcome in patients with
      atrial fibrillation undergoing percutaneous coronary intervention.
AB  - INTRODUCTION: CHADS2 and CHA2DS2-VASc scores are used to estimate thromboembolic
      risk in atrial fibrillation (AF). HAS-BLED is recommended for bleeding risk
      prediction. Their value in predicting the outcome of AF patients after
      percutaneous coronary intervention (PCI) is unknown. Thus, our aim was to assess
      whether these simple risk scores are useful in predicting outcome in these
      patients. MATERIALS AND METHODS: AFCAS is an observational, multicenter,
      prospective registry including patients (n=929) with AF referred for PCI. Primary
      study endpoints were 1) all cause mortality; 2) major adverse events (all-cause
      mortality, myocardial infarction, repeat revascularization, stent thrombosis,
      transient ischemic attack, stroke or other arterial thromboembolism; MACCE); and
      3) bleeding at 12 months follow-up. CHADS2 and CHA2DS2-VASc scores and a modified
      HAS-BLED (mHAS-BLED) score (omitting labile INR and liver function) were
      calculated. RESULTS: Patients were distributed as follows: CHADS2 low 29.5%,
      intermediate 55.2%, high 15.3%; CHA2DS2-VASc low 9.6%, intermediate 46.0%, high
      44.5%. A high CHA2DS2-VASc score was predictive of all-cause mortality (p=0.02),
      whereas CHADS2 was not. High CHA2DS2-VASc score predicted MACCE (HR 2.24, 95%CI
      1.21-4.17, p=0.01), as did a high CHADS2 score (HR 1.60, 95%CI 1.05-2.45,
      p=0.029). Their predictive performance was only modest (C indexes 0.56-0.57).
      CHADS2 or CHA2DS2-VASc scores were not associated with bleeding. High mHAS-BLED
      scores (>=3) were not associated with any of the study outcomes. CONCLUSIONS:
      High CHA2DS2-VASc score was the best predictor of thrombotic outcomes after PCI
      in a high risk AF population. High mHAS-BLED score was not predictive of bleeding
      events. More accurate, simple risk scores are needed.

PMID- 24461144
TI  - Right ventricular dysfunction in hemodynamically stable patients with acute
      pulmonary embolism.
AB  - BACKGROUND: Echocardiography for risk stratification in hemodynamically stable
      patients with pulmonary embolism (PE) is well-established. Right ventricular
      dysfunction (RVD) is associated with an elevated mortality and adverse outcome.
      The aim of our study was to compare RVD criteria and investigate the role of
      elevated systolic pulmonary artery pressure (sPAP) in the diagnosis of RVD.
      METHODS: We retrospectively analyzed the echocardiographic and laboratory data of
      all hemodynamically stable patients with confirmed PE (2006-2011). The data were
      compared with three different definitions of RVD: Definition 1: RV dilatation,
      abnormal motion of interventricular septum, RV hypokinesis or tricuspid
      regurgitation. Definition 2: as with definition 1 but including elevated sPAP
      (>30mmHg). Definition 3: elevated sPAP (>30mmHg) as single RVD criterion.
      RESULTS: A total number of 129 patients (59.7% women, age 70.0years (60.7/81.0))
      were included in this study. Median Troponin I level was measured as 0.02ng/ml
      (0/0.14); mean sPAP 33.9+/-18.5mmHg. The troponin cut-off levels for predicting a
      RVD of the 3 RVD definitions were in definition 1-3: >0.01ng/ml, >0.01ng/ml and
      >0.00ng/ml. Analysis of the ROC curve showed an AUC for RVD definitions 1-3:
      0.790, 0.796 and 0.635. CONCLUSIONS: The combination of commonly used RVD
      criteria with added elevated sPAP improves the diagnosis of RVD in acute PE.
      Troponin I values of >0.01ng/ml in acute PE point to an RVD.

PMID- 24461155
TI  - 50 Years ago in the Journal of Pediatrics: A newly recognized syndrome of
      multiple congenital anomalies.

PMID- 24461154
TI  - AMIGO: a novel approach to the mentorship gap in pediatric rheumatology.

PMID- 24461156
TI  - 50 Years ago in the Journal of Pediatrics: An analysis of reasons for
      institutionalizing children with mongolism.

PMID- 24461157
TI  - 50 Years ago in the Journal of Pediatrics: Treatment of painful crises of sickle
      cell disease.

PMID- 24461158
TI  - 50 Years ago in the Journal of Pediatrics: In recognition of a dual career:
      pediatrician and academician.

PMID- 24461159
TI  - 50 Years ago in the Journal of Pediatrics: Dermatomyositis.

PMID- 24461160
TI  - The impact of hepatitis C burden: an evidence-based approach.
AB  - BACKGROUND: Infection with the hepatitis C virus (HCV) has been considered a
      major cause of mortality, morbidity and resource utilisation in the US. In
      addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent
      developments in the diagnosis and treatment of HCV, including new recommendations
      pertaining to screening for HCV by the Centers for Disease Control and Prevention
      and newer treatment regimens with high efficacy, short duration and the potential
      for interferon-free therapies, have energised the health care practitioners
      regarding HCV management. AIM: To assess the full impact of HCV burden on
      clinical, economic and patient-reported outcomes. METHODS: An expert panel was
      convened to assess the full impact of HCV burden on a number of important
      outcomes using an evidence-based approach predicated on Grading of
      Recommendations Assessment, Development and Evaluation methodology. The
      literature was summarised, graded using an evidence-based approach and presented
      during the workshop. Workshop presentations were intended to review recent,
      relevant evidence-based literature and provide graded summary statements
      pertaining to HCV burden on topics including the relationships between HCV and
      the development of important outcomes. RESULTS: The associations of HCV with
      cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus,
      rheumatological diseases and quality of life impairments are supported by strong
      evidence. Also, there is strong evidence that sustained viral eradication of HCV
      can improve important outcomes such as mortality and quality of life.
      CONCLUSIONS: The current evidence suggests that HCV has been associated with
      tremendous clinical, economic and quality of life burden.

PMID- 24461161
TI  - Plaque Accumulation Beneath Maxillary All-on-4TM Implant-Supported Prostheses.
AB  - BACKGROUND: Maxillary prostheses supported by four implants, following the All-on
      4(TM) principles, have become an accepted effective treatment for totally
      edentulous patients. Maintaining the hygiene of such fixed implant-supported
      prostheses is challenging. PURPOSE: The purpose of this clinical study was to
      evaluate the distribution of plaque on the fitting surface of All-on-4 fixed
      prostheses in order to find new strategies for maintaining their hygiene.
      MATERIALS AND METHODS: Twenty All-on-4 maxillary fixed prostheses collected from
      20 patients, 6 months after delivery, were stained with methylene blue to
      disclose plaque accumulation at the fitting surfaces of the prostheses. Digital
      photographs of the fitting surfaces of the prostheses were recorded and
      processed. The distribution of accumulated plaque was evaluated statistically.
      RESULTS: The average percentage of area covered with plaque was 28 +/- 8% of the
      total area of the fitting surface of the prostheses. The fitting surfaces of the
      prostheses had three times more plaque on the palatal area (52.5 +/- 7.33%) than
      on the buccal area (17.3 +/- 7.33%, p < .05). The interimplant proximal areas of
      the fitting surface covered with plaque were high when the distance between
      implants was short (r = -0.326, p = .014). CONCLUSION: These findings suggest
      that the hygiene of the All-on-4 prostheses could be improved by maximizing the
      distances between the inserted implants in the jaw, minimizing the prostheses'
      palatal extension and guiding patients to optimize their oral hygiene practices
      targeting the palatal area of their prostheses.

PMID- 24461163
TI  - An outpatient clinical study of dissociative disorder not otherwise specified.
AB  - The relatively high prevalence of the diagnosis of dissociative disorder not
      otherwise specified is frequently considered to be disproportionate. The
      disproportionate rate of this diagnosis is thought to be related to nosologic
      and/or diagnostic issues in dissociative identity disorder. We sought to
      investigate and compare the symptom patterns of these two clinical entities. We
      conducted a cross-sectional study involving 1314 participants who were screened
      with the Dissociative Experience Scale (DES) and the Somatoform Dissociation
      Questionnaire (SDQ). Of the participants, 272 who scored above the cut-off points
      for the screening questionnaires (DES score>30 and/or SDQ score>40 points) were
      invited to complete a structured interview using the Dissociative Disorders
      Interview Schedule (DDIS); of this subsample, only 190 participants agreed to
      participate in the second phase of the study. The mean score for the DES was
      18.55+/-17.23, and the mean score for the SDQ was 30.19+/-13.32. Of the 190
      participants, 167 patients were diagnosed as having a dissociative disorder
      (87.8%). We found that DD-NOS was the most prevalent category of dissociative
      disorder. There was a significantly larger percentage of patients in the DID
      group than in the DD-NOS group according to secondary features of DID and
      Schneiderian symptoms. The secondary features of DID and Schneiderian symptoms
      appeared to be more specific for DID, while no differences were detected between
      DID and DD-NOS based on most of the items on the SCL 90R. Further longitudinal
      studies are needed to determine the features that are similar and dissimilar
      between DD-NOS and DID.

PMID- 24461162
TI  - Is cognitive behaviour therapy of benefit for melancholic depression?
AB  - OBJECTIVE: This paper seeks to determine the relevance and likely salience of
      cognitive behaviour therapy (CBT) as a treatment for melancholic depression.
      METHODS: The findings of a randomised trial comparing 12-week outcome of 18
      patients with melancholic depression receiving antidepressant medication and 11
      receiving CBT were evaluated, and qualitative explanations for the outcomes were
      provided principally by the treating CBT practitioners. RESULTS: In the trial,
      CBT showed no improvement in depression severity in the first four weeks and then
      some level of improvement over the subsequent eight weeks. Outcome was superior
      for those receiving antidepressant medication at 12 weeks and was first
      demonstrated at four weeks. The benefits of CBT appeared to be in settling
      anxiety, dealing with cognitive processing of having a melancholic depression and
      addressing any personality vulnerabilities. CONCLUSION: While a pilot study, our
      qualitative reports indicate that CBT may provide a useful role in managing
      melancholia as an adjunct to antidepressant medication. Future studies examining
      such a combination treatment model should seek to determine if indicative data
      provided here argue for a sequencing model of CBT being introduced after
      medication has addressed core biological underpinnings.

PMID- 24461164
TI  - Neuroscientific evidence for contextual effects in decision making.
AB  - Both internal and external states can cause inconsistencies in decision behavior.
      I present examples from behavioral decision-making literature and review
      neuroscientific knowledge on two contextual influences: framing effects and
      social conformity. The brain mechanisms underlying these behavioral adjustments
      comply with the dual-process account and simple learning mechanisms, and are weak
      indicators for unintentionality in decision-making processes. 

PMID- 24461165
TI  - Multivariate adaptive regression splines analysis to predict biomarkers of
      spontaneous preterm birth.
AB  - OBJECTIVE: To develop classification models of demographic/clinical factors and
      biomarker data from spontaneous preterm birth in African Americans and
      Caucasians. DESIGN: Secondary analysis of biomarker data using multivariate
      adaptive regression splines (MARS), a supervised machine learning algorithm
      method. SETTING: Analysis of data on 36 biomarkers from 191 women was reduced by
      MARS to develop predictive models for preterm birth in African Americans and
      Caucasians. SAMPLES: Maternal plasma, cord plasma collected at admission for
      preterm or term labor and amniotic fluid at delivery. METHODS: Data were
      partitioned into training and testing sets. Variable importance, a relative
      indicator (0-100%) and area under the receiver operating characteristic curve
      (AUC) characterized results. RESULTS: Multivariate adaptive regression splines
      generated models for combined and racially stratified biomarker data. Clinical
      and demographic data did not contribute to the model. Racial stratification of
      data produced distinct models in all three compartments. In African Americans
      maternal plasma samples IL-1RA, TNF-alpha, angiopoietin 2, TNFRI, IL-5,
      MIP1alpha, IL-1beta and TGF-alpha modeled preterm birth (AUC train: 0.98, AUC
      test: 0.86). In Caucasians TNFR1, ICAM-1 and IL-1RA contributed to the model (AUC
      train: 0.84, AUC test: 0.68). African Americans cord plasma samples produced IL
      12P70, IL-8 (AUC train: 0.82, AUC test: 0.66). Cord plasma in Caucasians modeled
      IGFII, PDGFBB, TGF-beta1 , IL-12P70, and TIMP1 (AUC train: 0.99, AUC test: 0.82).
      Amniotic fluid in African Americans modeled FasL, TNFRII, RANTES, KGF, IGFI (AUC
      train: 0.95, AUC test: 0.89) and in Caucasians, TNF-alpha, MCP3, TGF-beta3 ,
      TNFR1 and angiopoietin 2 (AUC train: 0.94 AUC test: 0.79). CONCLUSIONS:
      Multivariate adaptive regression splines models multiple biomarkers associated
      with preterm birth and demonstrated racial disparity.

PMID- 24461168
TI  - [Adverse events following immunization and causality assessment of an adverse
      event following immunization].
AB  - Several fatal events occurred in Hunan, Guangdong and Sichuan Province in
      December, 2013. The events were reported by the news media, which followed
      growing public concern. Currently, more and more vaccines were developed and the
      immunization was adopted for more objectives. The clinicians, especially
      pediatricians will face a growing number of clinical problems related to the
      vaccine. The clinicians should pay attention to learn more knowledge about
      vaccines. This article describes the definition and classification of "adverse
      events following immunization" and "serious vaccine product-related reactions",
      and the signifcance and conclusion of causality assessment following
      immunization. 

PMID- 24461167
TI  - Salmonella isolated from individual reptiles and environmental samples from
      terraria in private households in Sweden.
AB  - BACKGROUND: This study investigates Salmonella spp. isolated from privately kept
      reptiles and from environmental samples such as bedding materials or water from
      the floor of the enclosures (terraria). It also compares isolation of Salmonella
      using Modified Semisolid Rappaport-Vassiliadis (MSRV) medium or selective
      enrichment in Rappaport-Vassiliadis-Soya (RVS) pepton broth. Cloacal swabs or
      swabs from the cloacal area were collected from 63 individual reptiles belonging
      to 14 households. All reptiles were from different terraria and from 62 of these,
      environmental samples were also collected. Sampling were done by the reptile
      owners according to written instructions and sent by mail immediately after
      sampling. All but three samples were analyzed within 24 h after collection.
      Colonies suspected for Salmonella were tested for agglutination and serotyped
      using the White-Kauffmann-Le Minor scheme. The relative sensitivity (se) and
      specificity (sp) for MSRV compared with RVS, and the agreement coefficient kappa
      (kappa) were calculated. RESULTS: Salmonella was isolated from 50/63 (80%)
      terraria, either from the reptiles (31/63; 49%) or from bedding material (39/62;
      63%). The most common subspecies was Salmonella enterica subspecies enterica
      followed by S. enterica subspecies diarizonae. In reptiles, the most common S.
      enterica subspecies enterica serovars were Java (n = 4) and Fluntern (n = 4),
      compared with the serovars Tennessee (n = 10) and Fluntern (n = 10) in the
      environmental samples. The exact same set of Salmonella subspecies and serovars
      were not isolated from the individual reptiles and the environmental samples from
      any of the households. Isolation using MSRV yielded more Salmonella isolates
      61/113 (54%) than enrichment in RVS 57/125 (46%). The se was 97.9% (95%
      Confidence Interval 93.9-100), the sp 78.5% (95% CI 68.5-88.5) and the kappa
      0.74, indicating substantial agreement between the tests. CONCLUSIONS: Salmonella
      can be expected to be present in environments where reptiles are kept. This
      constitutes public health risks and should be considered during handling of the
      reptiles and during cleaning and disposal of bedding. A combination of different
      culturing techniques may be used to increase the isolation rate.

PMID- 24461169
TI  - [Research advance in assessment of nutritional status of children].
AB  - Malnutrition is not a simple disease, which occurs in the condition when the body
      does not get the right amount of nutrients to maintain healthy tissues and organ
      functions. Malnutrition generally refers both to undernutrition and
      overnutrition, but usually it is used to refer solely to a deficiency of
      nutrition. Infants and young children are the most vulnerable because of their
      high nutritional requirements for growth and development. Growth is an important
      indicator of health and nutritional status of a child. Generally, underweight,
      studding and wasting are used as the indicators of malnutrition. In fact, a gain
      in height is a better indicator of the adequacy of a diet than a gain in weight.
      Rates of weight gain needs to accompany accelerated height gain to maintain
      normal body proportions (weight-for-height). Now therefore WHO recommends using
      weight-for-height as the indicator of malnutrition of epidemic intensity in
      communities and of nutritional condition evaluation, including treatment
      assessment. The assessment of nutritional status is commonly summarized by the
      mnemonic "ABCD," which stands for anthropometric measurement (A), biochemical or
      laboratory tests (B), clinical indicators (C) and dietary assessment (D).
      Children with malnutrition are required to ingest more than 30 essential
      nutrients including both functional, protective nutrients (type I) and growth
      nutrients (type II), in order to have a catch-up growth in weight and height. 

PMID- 24461170
TI  - [Efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA
      PKU2) in 1-8 year-old children with phenylketonuria: a prospective, open, self
      controlled and multi-center study in China].
AB  - OBJECTIVE: To evaluate the efficacy and safety of a phenylalanine-free amino acid
      based enteral formula (AA-PKU2) in the treatment of children with phenylketonuria
      (PKU) aged 1-8 years. METHODS: A prospective, open, self-controlled, multi-center
      trial was performed, enrolling 121 PKU children (1-8 years in age) consecutively
      between July, 2009 and May, 2011. Enteral nutrition therapy was administered for
      32 weeks. The data on blood phenylalanine (PHE) levels, metal development,
      weight, height, head circumference, serum nutritional biomarkers (total protein,
      pre-albumin, albumin, total cholesterol, total triglyceride, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol), and measurements
      from routine blood and urine examinations and from renal and hepatic function
      tests were collected before the therapy and at 8 weeks and 32 weeks after the
      therapy and were comparatively analyzed. RESULTS: The mean blood PHE level at 8
      and 32 weeks of AA-PKU2 treatment was 353+/-253 and 361+/-280 umol/L
      respectively, significantly lower than that before the treatment (487+/-327
      umol/L; P<0.01). The difference in intelligence quotient scores before and after
      AA-PKU2 treatment was not significant (P>0.05) when assessed by the Gesell tests
      in children aged 1-4 years but significant (P<0.01) when assessed by WPPSI or
      WISR-R tests in children over 4 years. The average height, weight and head
      circumference at 8 and 32 weeks after treatment were significantly increased as
      compared to these measurements before treatment (P<0.01) with absolute levels
      similar to those in the control children. In contrast, the mean values of total
      protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density
      lipoprotein cholesterol and high-density lipoprotein cholesterol at both time
      points were not different either from those prior to the treatment or from those
      in the control children. Mild diarrhea was the adverse events associated with AA
      PKU2 treatment, which occurred in 3 (2.5%) cases. All these 3 patients fully
      recovered without treatment. CONCLUSIONS: The phenylalanine-free amino acid-based
      formula, AA-PKU2, is effective and safe in controlling blood PHE levels and
      improving mental development with adequate nutritional support in PKU.

PMID- 24461171
TI  - [Risk factors for nutritional iron deficiency anemia in children].
AB  - OBJECTIVE: To investigate the clinical features of nutritional iron deficiency
      anemia (IDA) and analyze the risk factors for the severity of anemia, and to
      provide a basis for the prevention and clinical diagnosis and treatment of this
      disease. METHODS: A retrospective analysis was performed on the clinical data of
      372 children with IDA to investigate the risk factors for the severity of IDA.
      RESULTS: Of 372 cases, the male-to-female ratio of these patients was 2.72 : 1.
      Of all cases, 79.9% were aged 6 months to 2 years, and 30.7% were premature
      infants; 22.9% had a birth weight of < 2.5 kg, and 77.1% had a birth weight of
      >=2.5 kg; 36.0% were delivered by natural birth, and 64.0% were delivered by
      caesarean section; 79.3% were not given solid foods in time; 46.2% had a history
      of lower respiratory tract infection/recurrent upper respiratory tract infection,
      diarrhea, trauma, or surgery. The univariate analysis showed that age, birth
      weight, gestational age, timely introduction of solid foods, and a history of
      lower respiratory tract infection/recurrent upper respiratory tract infection,
      diarrhea, trauma, or surgery were associated with the severity of anemia. The
      multivariate analysis showed that birth weight and the mentioned medical history
      were associated with the severity of anemia. CONCLUSIONS: Nutritional IDA is
      common in children aged 6 months to 2 years. Nowadays, improper feeding pattern
      is still one of the main causes of IDA. Birth weight and a history of lower
      respiratory tract infection/recurrent upper respiratory tract infection,
      diarrhea, trauma, or surgery are closely associated with the severity of anemia.

PMID- 24461172
TI  - [Leptin gene C2549A polymorphism in minority Hui and Uygur children with
      obesity].
AB  - OBJECTIVE: To investigate the relationship of leptin gene polymorphism with
      obesity in ethnic minority Hui and Uygur children in China. METHODS: Sixty-eight
      ethnic minority (35 Hui and 33 Uygur) children with obesity and 69 age-matched
      minority (36 Hui and 33 Uygur) children without obesity were recruited from six
      primary schools in the sub-urban areas of Urumqi. Venous blood was sampled from
      all subjects after fasting for 12 hours. Leptin gene C2549A polymorphism was
      determined by polymerase chain reaction (PCR) and restriction fragment length
      polymorphism methods. Blood concentrations of lipids, leptin and insulin were
      measured with biochemical methods and radioimmunoassys, respectively. RESULTS: In
      the 137 children tested, the prevalence of AA, AC and CC genotype was 9.5%, 33.6%
      and 56.9%, respectively. A allele frequency was significantly different between
      the two ethnic (i.e. Hui and Uygur) groups (P<0.05). A allele frequency and AA+
      AC genotype frequency were not significantly different between obese and non
      obese children in both ethnic groups (P>0.05). Blood leptin levels were not
      significantly different between obese and non-obese children with an AA+AC or CC
      genotype in both ethnic groups (P>0.05). CONCLUSIONS: Leptin gene polymorphisms
      exist in Hui and Uygur children. The C2549A polymorphism is not significantly
      associated with the prevalence of obesity in both Hui and Uygur children.

PMID- 24461174
TI  - [Changes in T lymphocyte subsets in preterm infants with intrauterine growth
      retardation].
AB  - OBJECTIVE: To study changes in T lymphocyte subsets in preterm infants with
      intrauterine growth retardation (IUGR). METHODS: The study enrolled 29 IUGR
      preterm infants, 38 preterm infants born appropriate for gestational age (AGA),
      and 20 healthy full-term infants. Peripheral blood was sampled during the first
      24 hours of life, and again at a corrected age of 38 weeks of the preterm
      infants. T lymphocyte subsets were analyzed by flow cytometry, and absolute
      counts of leukocytes, total lymphocytes, and T lymphocytes were determined with
      an automated hematology analyzer. RESULTS: Within the first 24 hours of life,
      percentages of CD3(+) and CD4(+) were lower in IUGR preterm infants than in AGA
      preterm infants and full-term infants (P<0.05), percentages of CD8(+) and
      CD4(+)/CD8(+) ratio were lower in IUGR preterm infants than in full-term infants
      (P<0.05), and percentages of CD3(+), CD4(+) and CD4(+)/CD8(+) ratio were lower in
      AGA preterm infants than in full-term infants (P<0.05). Moreover, the absolute
      counts of total lymphocytes were lower in IUGR preterm infants than in full-term
      infants (P<0.05); the absolute counts of T lymphocytes were lower in preterm
      infants, regardless of IUGR, than in full-term infants (P<0.05), and lower in
      IUGR infants than in AGA infants (P<0.05). At the corrected age of 38 weeks,
      percentages of CD3(+), CD4(+) and CD4(+)/CD8(+) ratio were increased in both IUGR
      and AGA infants as compared to the measurements within the first 24 hours of life
      (P<0.05), and percentages of CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) ratio were
      lower in IUGR infants than in AGA infants (P<0.05), whereas there were no
      significant differences in counts of leukocytes, total lymphocytes and T
      lymphocytes between IUGR and AGA infants (P>0.05). CONCLUSIONS: There may be a
      certain degree of compromise in cell-mediated immunity in preterm infants with
      IUGR and this compromise may last to 38 weeks after birth.

PMID- 24461173
TI  - [Effects of gonadotropin releasing hormone analog and growth hormone on height in
      girls with idiopathic central precocious puberty].
AB  - OBJECTIVE: To determine the effect of gonadotropin releasing hormone agonist
      (GnRHa), by itself alone or in combination with recombinant human growth hormone
      (rhGH), on height in young girls (bone age>=10 years) with idiopathic central
      precocious puberty (ICPP). METHODS: Eighty girls with ICPP (9.0+/-0.7 years old)
      from six medical centers across Southeast and Southwest China participated in
      this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa
      (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18 +/-0.53 years)
      were treated with GnRHa for 25.29+/-6.92 months and rhGH for 12.87+/-7.02 months.
      Girls in the GnRHa group (bone age 11.03 +/-0.50 years) were treated with GnRHa
      for 25.96+/-8.95 months. The height standard deviation for bone age (HtSDS-BA),
      predicted adult height, near-adult height and net height increase before and
      after treatment were recorded for girls in both groups. RESULTS: HtSDS-BA was
      significantly improved after treatment for both groups (P<0.01) and the HtSDS-BA
      value was superior in the GnRHa+rhGH group over the GnRHa group (P<0.01). Values
      in near adult height (157+/-6 cm vs 157+/-4 cm), net height increase after
      treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal
      (161+/-5 cm vs 158+/-5 cm) were higher in the GnRHa+rhGH group than the GnRHa
      group, but the differences were not significant. CONCLUSIONS: Both GnRHa plus
      rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a
      bone age >=10 years to a similar extent. Adult height predicted based on bone age
      in ICPP girls following drug withdrawal is usually overestimated and precautions
      should be taken when this parameter is used.

PMID- 24461175
TI  - [Early multi-disciplinary intervention reduces neurological disability in
      premature infants].
AB  - OBJECTIVE: This study aimed to evaluate the effectiveness of multi-disciplinary
      treatment approaches in reducing neurological disabilities in premature infants.
      METHODS: A total of 117 infants who were born premature in our hospital between
      March 2008 and February 2010 but had no congenital malformations and no severe
      neonatal complications, were enrolled in this study. They were randomly allocated
      to a multi-disciplinary treatment group (n=63) and a control group (n=54). While
      patients in the control group underwent an early conventional treatment, those in
      the multi-disciplinary treatment group were subjected to regular development
      monitoring, neurological examination and screening for brain injury, neuro
      nutrition and neurodevelopment therapies, and rehabilitation training. RESULTS:
      The incidence rates of abnormalities in posture, reflex, sleep, muscle tone and
      EEG were significantly lower in the multi-disciplinary treatment group than in
      the control froup (P<0.05) at corrected postnatal ages of 6-12 months. At
      corrected postnatal ages of 6, 12, 18 and 24 months, both mental development
      index (MDI) and psychomotor development index (PDI) scores were significantly
      higher in the multi-disciplinary treatment group than in the control group
      (P<0.05). At corrected postnatal age of 3 years, incidence rates of cerebral
      palsy, language barrier, abnormal muscle tone and hearing impairment were
      significantly lower in the multi-disciplinary treatment group than in the control
      group (P<0.05). CONCLUSIONS: Early multi-disciplinary intervention approaches may
      significantly improve mental and motor developments and reduce the incidence of
      cerebral palsy-associated neurological disabilities in premature infants.

PMID- 24461176
TI  - [Clinical importance of preoperative measurement of plasma amino-terminal pro-B
      type natriuretic peptide in infants with congenital heart disease].
AB  - OBJECTIVE: To define cut-off values of plasma amino-terminal pro-B-type
      natriuretic peptide (NT-ProBNP) for the diagnosis of congenital heart failure
      (CHF) and evaluate the importance of plasma NT-ProBNP measurement in the
      assessment of cardiac function prior to heart surgery in infants with congenital
      heart disease (CHD). METHODS: Plasma levels of NT-proBNP were measured in 120
      infants with CHD before heart surgery and in 100 age-matched healthy infants
      between June 2010 and June 2013. The data were stratified based on the presence
      or absence of CHF in the whole group of CHD infants and on age (i.e., <1 year and
      >=1 year) and time (i.e., before surgery) within the subgroup of CHF infants.
      RESULTS: Of the 120 infants with CHD, 41 met the criteria for CHF defined in the
      Ross Classification for Heart Failure in Infants.The cut-off values of plasma NT
      ProBNP were >=498 ng/L for infants of all ages, 557 ng/L for <1 year age group
      and 452 ng/L for >=1 year age group, respectively, in the 41 CHF patients. In CHF
      infants, plasma NT-proBNP was significantly decreased after protecting of cardiac
      function (P<0.001). CONCLUSIONS: The cut-off values of plasma NT-ProBNP for CHF
      differ between infants <1 year and infants >=1 year. Moreover, plasma NT-ProBNP
      can be used as an additional parameter in the preoperative assessment of cardiac
      function in CHD infants.

PMID- 24461177
TI  - [Changes in serum levels of resistin and visfatin in pediatric patients with
      acute Kawasaki disease following intravenous immune globulin treatment].
AB  - OBJECTIVE: To determine serum levels of resistin and visfatin in the patients
      with acute Kawasaki disease before and after intravenous immune globulin (IVIG)
      treatment. METHODS: A total of 50 children with acute Kawasaki disease were
      treated with IVIG for 48 hours between January 2011 and January 2013. As
      controls, 30 healthy children and 30 children with acute infectious diseases were
      included. Serum levels of resistin and visfatin were measured by ELISA both
      before and after the treatment. RESULTS: The baseline serum levels of resistin
      and visfatin were significantly higher in patients with acute Kawasaki disease
      than in the two control groups of subjects (i.e., healthy children and patients
      with acute infectious diseases; P<0.05). In the 50 patients with Kawasaki
      disease, 38 were not responding and 12 were responding. Serum resistin levels
      before treatment were significantly higher in non-responders than those in
      responders (P<0.05). A significant decrease in serum levels of resistin after
      treatment was observed in IVIG responders (P<0.05). Serum visfatin levels were
      not significantly different between IVIG responders and non-responders (P>0.05).
      Additionally, serum resistin and visfatin levels were not significantly different
      between acute Kawasaki disease patients with and without coronary artery lesions.
      CONCLUSIONS: Resistin and visfatin may play important roles in the development of
      Kawasaki disease and serum resistin may be used as a novel outcome indicator of
      the IVIG treatment.

PMID- 24461178
TI  - [Expression of myeloid-related protein complex in association with circulating
      endothelial cells in children with acute Kawasaki disease].
AB  - OBJECTIVE: To investigate the expression of myeloid-related protein complex (MRP
      8/14) in children with acute Kawasaki Disease (KD). METHODS: A total of 41
      children with acute KD and 40 age- and sex-matched control children with upper
      respiratory tract infection were recruited. Serum levels of MRP-8/MRP-14 complex
      were measured by ELISA, messenger ribonucleic acid (mRNA) abundance of MRP-8 and
      MRP-14 in circulating granulocytes and monocytes was determined by RT-PCR, and
      the number of circulating endothelial cells was determined by flow cytometry.
      RESULTS: When the analysis was stratified according to the presence or absence of
      coronary artery ectasia in the KD patient group, serum levels of MRP-8/MRP-14
      complex, MRP-8 and MRP-14 mRNA abundance in granulocytes, and the number of
      circulating endothelial cells were all significantly higher in KD patients with
      coronary artery ectasia than in KD patients without coronary artery ectasia
      (P<0.05). Serum levels of MRP-8/MRP-14 complex were positively correlated with
      the number of endothelial cells in the circulation (r=0.69, P<0.05). CONCLUSIONS:
      Serum levels of MRP-8/MRP-14 complex are elevated in a positive association with
      the number of circulating endothelial cells in KD children with coronary artery
      ectasia, suggesting a causative role in the development of coronary artery
      lesions.

PMID- 24461179
TI  - [Clinical and immunological features of lupus nephritis in children:
      retrospective analysis of 40 cases].
AB  - OBJECTIVE: To analyze the clinical and immunological features of children with
      lupus nephritis (LN). METHODS: Chart records of 40 (4 male and 36 female) LN
      children who were admitted consecutively between January, 2005 and December, 2010
      were reviewed. The baseline demographic, pathological and immunological data were
      analyzed. RESULTS: In the 40 LN patients analyzed, the mean age of the disease
      onset was 10.6 +/- 2.6 (range from 2.6 to 14.3) years, and 35 cases (88%) were
      school-age children. Proteinuria was detected in all 40 cases, including
      nephrotic-range proteinuria in 12 (30%) cases, and isolated proteinuria in 9
      (22%) cases. Twenty-six (65%) patients had varying degrees of hematuria. Acute
      nephritis was the most common sub-type, accounting for 47% of the total cases.
      Among the 39 cases undergoing renal biopsy, 3 were unclassified and the remaining
      36 were classified, respectively, as type IV LN (50%, 18 cases), type II LN (22%,
      8 cases). In the histopathologcally classified case, 100% were antinuclear
      antibody-positive, 61% were anti-dsDNA-positive, and 89% showed varying degrees
      of decrease in serum C3 and C4 concentrations. Following treatment for 6 months,
      a high LN remission rate (95%) was achieved; the acute renal activity index
      remained higher in IV, V+III and V+IV subtypes than in other subtypes, while the
      chronic index and the degree of tubulointerstitial damage were not different
      between histopathological subtypes. CONCLUSIONS: The clinical manifestations of
      LN children are diverse. Clinically, acute nephritis is the most common form of
      LN in children. Histopathologically, type IV is the most frequent subtype of LN.
      Early treatment may result in significant disease remission.

PMID- 24461180
TI  - [Serious systemic adverse events associated with allergen-specific immunotherapy
      in children with asthma].
AB  - OBJECTIVE: To retrospectively assess serious systemic adverse effects of
      standardized dust-mite vaccine in children with asthma. METHODS: Medical records
      of 704 children (5-17 years in age) with asthma between January, 2005 and
      December, 2011 were reviewed. Serious systemic adverse events following treatment
      with a standardized dust-mite vaccine in these children were analyzed. RESULTS: A
      total of 336 systemic adverse reactions were observed in 17.0% (120/704) of the
      patients analyzed of these adverse reactions, 18 (5.4%) were serious (level 3),
      318 (94.6%) were not serious (below level 3), and no single case of anaphylactic
      shock (level 4) was recorded. Systemic adverse events occurred most frequently in
      the 5 to 11-year age group and in the summer season (from June to August). In the
      18 severe cases, the peak expiratory flow (PEF) dropped by 20% immediately after
      the vaccine injection, and other major clinical symptoms included cough, wheezing
      and urticaria. All children with serious systemic adverse effects were given
      inhaled hormone and atomized short-acting beta agonists, oral antihistamines,
      intravenous dexamethasone and/or intramuscular adrenaline. After these
      treatments, the clinical symptoms were significantly relieved. CONCLUSIONS: The
      rate of serious systemic adverse events following allergen-specific immunotherapy
      is relatively low in children with allergic asthma. Conventional medications are
      effective in managing these immunotherapy-associated adverse events.

PMID- 24461181
TI  - [Methylenetetrahydrofolate reductase deficiency-induced schizophrenia in a school
      age boy].
AB  - Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal
      recessive disorder. It is known that MTHFR deficiency may result in
      hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely
      reported. Here we present the clinical course, biochemical and genetic
      characteristics of schizophrenia resulted from MTHFR deficiency in a school-age
      boy. He was 13 years old. He was admitted with a two-year history of fear,
      auditory hallucination, learning difficulty, sleeping problems, irascibility,
      drowsing and giggling. At admission, he had significantly elevated plasma and
      urine levels of total homocysteine, significantly decreased levels of folate in
      serum and cerebrospinal fluid, and a normal blood concentration of methionine.
      Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR
      gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia
      and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was
      initiated. After the treatment for 1 week, his plasma and urine levels of
      homocysteine were decreased to a normal range and the clinical symptoms were
      significantly improved. After 3 months of treatment, the patient returned to
      school. He is now living with normal school life. In summary, children with late
      onset MTHFR deficiency and secondary cerebral folate deficiency may lead to
      schizophrenia. This rare condition can be early diagnosed through analyses of
      blood and urine total homocysteine, amino acids in blood and folate in blood and
      cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin
      B12 and betaine. 

PMID- 24461182
TI  - [Neuroregeneration of newborn rats with hypoxic-ischemic brain damage following
      antibody-mediated neutralization of paired-immunoglobulin-like receptor B].
AB  - OBJECTIVE: To study changes in paired-immunoglobulin-like receptor B (PirB)
      expression after hypoxic-ischemic brain damage (HIBD) as well as the role for
      targeted inhibition of PirB activity in nerve regeneration in rats. METHODS:
      Newborn Sprague-Dawleyrats rats were divided into: a sham operation group (n=30),
      a HIBD group (n=30), and an anti PirB antibody treatment group (n=6). In the HIBD
      group, HIBD was induced by right carotid artery ligature and subsequent exposure
      to hypoxia (8% O2) for 3 hours. In the sham operation group, right carotid artery
      was dissected as in the HIBD group but no ligature and hypoxic exposure was not
      applied. In the two groups, 6 animals were sacrificed at 0, 6, 12, 24 and 72
      hours after the operation and hypoxic exposure. In the antibody treatment group,
      after carotid artery ligation and hypoxia exposure as in the HIBD group, an anti
      PirB antibody was injected intracerebrally and animals were sacrificed 72 hours
      after the injection. Immediately after sacrifice of the animals at designated
      time points, brain tissue specimens were collected. The presence and content of
      PirB protein were assessed by immunohistochemistry and Western blot analysis
      respectively, the abundance of PirB mRNA was determined by RT-PCR, and the Rho
      kinase (Rock) activity was determined by immunoprecipitation. RESULTS: At 72
      hours after operation, PirB mRNA abundance and protein content in the brain were
      significantly increased as compared with the measurements at 0 hour after
      operation in the HIBD group (P<0.05); ROCK activity was significantly increased
      in the HIBD group as compared with the sham operation and anti PirB antibody
      groups (P<0.05). CONCLUSIONS: PirB might be involved in HIBD through a Rho-ROCK
      dependent mechanism and antibody-mediated neutralization of PirB in the brain may
      offer a novel therapeutic strategy for HIBD.

PMID- 24461183
TI  - [Effect of integrin beta8 on TGF-beta1 activation in astrocytes with oxygen
      glucose deprivation].
AB  - OBJECTIVE: To study the effect of beta8 expression on transforming growth factor
      beta1(TGF-beta1) activation in astrocytes with oxygen glucose deprivation (OGD).
      METHODS: Astrocytes were cultured and then subjected to OGD to generate hypoxia
      ischemia (HI) model in vitro. Immunocytochemistry was used to detect the
      expression and distribution of beta8 in nomoxia cultured cells. beta8 protein
      expression was quantified by Western blot at 12 hours, 1 day and 2 days after
      OGD. Astrocytes and luciferase reporter cells (TMLC) were co-cultured. beta8 RNA
      interference system was established to specifically inhibit beta8 expression in
      cultured astrocytes. TGF-beta1 activation was then detected in the co-culture
      system. RESULTS: beta8 was mainly located in the cytoplasm and neurites of
      astrocytes. OGD resulted in increase of beta8 protein expression at 12 hours
      after reoxygenation in astrocytes, which was peaked at 1 day after reoxygenation.
      TGF-beta1 activation was in accordance with beta8 expression in astrocyte-TMLC co
      culture system after reoxygenation. After the inhibition of beta8, TGF-beta1
      activation was significantly reduced in all time points. CONCLUSIONS: The highly
      expressed beta8 plays important roles in the regulation of TGF-beta1 activation
      in neonatal rats with hypoxic-ischemic brain damage.

PMID- 24461184
TI  - [Treatment of severe acute pancreatitis by continous hemodiafiltration:
      experience of 3 cases].

PMID- 24461185
TI  - [Diagnosis and carrier screening of X-linked chronic granulomatous disease by DHR
      123 flow cytometry].

PMID- 24461186
TI  - [Mental symptoms as the first presentation of late-onset methylmalonic acidemia:
      report of 3 cases].

PMID- 24461187
TI  - [Glutaric aciduria type I: a report of 2 cases].

PMID- 24461188
TI  - [Recurrent cold injuries of right hand as the first presentation of
      syringomyelia: a case report].

PMID- 24461189
TI  - [Coexistence of growth hormone deficiency and lipodystrophia centrifugalis
      abdominalis infantilis in a child].

PMID- 24461190
TI  - [Biomarkers in acute lung injury].
AB  - Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is
      characterized by non-cardiogenic, acute and progressive respiratory failure
      mediated by a variety of injurious stimuli. ALI can progress to ARDS if an
      effective management is not taken. The mortality rate remains high due to the
      complex pathogenesis and ineffective management of ARDS. At present, effective
      treatment methods for ALI are not available and thus it is important to study the
      pathogenesis and early diagnosis of ALI. This article reviews some of the
      biomarkers associated with ALI, with a focus on early diagnosis and future
      studies. 

PMID- 24461191
TI  - [Recent advances in the research on mechanisms underlying podocyte-specific gene
      mutation-related steroid-resistant nephrotic syndrome].
AB  - Steroid-resistant nephrotic syndrome poses a significant clinical challenge. Its
      pathogenesis has not been fully elucidated. In recent years, numerous studies
      have shown that podocyte-specific gene mutations may play important roles in the
      development of steroid-resistant nephrotic syndrome. Among the identified genes
      mutated in podocytes include NPHS2, NPHS1, WT1, TRPC6, MDR1, PLCE1, LMX1B, and
      LAMB2. This review aims to summarize the characteristics of these mutated genes
      in podocytes. The putative role for these podocyte-specific mutated genes in the
      pathogenesis, diagnosis, treatment and prognosis of steroid-resistant nephrotic
      syndrome is also discussed. 

PMID- 24461192
TI  - Propensity score methods and unobserved covariate imbalance: comments on
      "squeezing the balloon".
AB  - In their recent Health Services Research article titled "Squeezing the Balloon:
      Propensity Scores and Unmeasured Covariate Balance," Brooks and Ohsfeldt (2013)
      addressed an important topic on the balancing property of the propensity score
      (PS) with respect to unmeasured covariates. They concluded that PS methods that
      balance measured covariates between treated and untreated subjects exacerbate
      imbalance in unmeasured covariates that are unrelated to measured covariates.
      Furthermore, they emphasized that for PS algorithms, an imbalance on unmeasured
      covariates between treatment and untreated subjects is a necessary condition to
      achieve balance on measured covariates between the groups. We argue that these
      conclusions are the results of their assumptions on the mechanism of treatment
      allocation. In addition, we discuss the underlying assumptions of PS methods,
      their advantages compared with multivariate regression methods, as well as the
      interpretation of the effect estimates from PS methods. 

PMID- 24461193
TI  - Genome-scale reconstruction of the sigma factor network in Escherichia coli:
      topology and functional states.
AB  - BACKGROUND: At the beginning of the transcription process, the RNA polymerase
      (RNAP) core enzyme requires a sigma-factor to recognize the genomic location at
      which the process initiates. Although the crucial role of sigma-factors has long
      been appreciated and characterized for many individual promoters, we do not yet
      have a genome-scale assessment of their function. RESULTS: Using multiple genome
      scale measurements, we elucidated the network of sigma-factor and promoter
      interactions in Escherichia coli. The reconstructed network includes 4,724 sigma
      factor-specific promoters corresponding to transcription units (TUs),
      representing an increase of more than 300% over what has been previously
      reported. The reconstructed network was used to investigate competition between
      alternative sigma-factors (the sigma70 and sigma38 regulons), confirming the
      competition model of sigma substitution and negative regulation by alternative
      sigma-factors. Comparison with sigma-factor binding in Klebsiella pneumoniae
      showed that transcriptional regulation of conserved genes in closely related
      species is unexpectedly divergent. CONCLUSIONS: The reconstructed network reveals
      the regulatory complexity of the promoter architecture in prokaryotic genomes,
      and opens a path to the direct determination of the systems biology of their
      transcriptional regulatory networks.

PMID- 24461194
TI  - New advances in the pathophysiologic and radiologic basis of the exstrophy
      spectrum.
AB  - The exstrophy-epispadias complex is a rare spectrum of anomalies affecting the
      genitourinary system, anterior abdominal wall, and pelvis. Recent advances in the
      repair of classic bladder exstrophy (CBE) and cloacal exstrophy (CE) have
      resulted in significant changes in outcomes of surgical management (including
      higher continence rate, fewer surgical complications, and better cosmesis) and
      health-related quality of life in these patients. These noteworthy changes
      resulted from advances in the pathophysiological and genetic backgrounds of this
      disease and better radiologic assessment of the three-dimensional anatomy of the
      bony pelvis and its musculature. A PubMed search was performed with the keyword
      exstrophy. The resulting literature pertaining to genetics, stem cells, imaging,
      tissue engineering, epidemiology, and endocrinology was reviewed. The following
      represents an overview of the advances in basic science understanding and imaging
      of the exstrophy-epispadias spectrum and discusses their possible and future
      effects on the management of CBE and CE. 

PMID- 24461196
TI  - [Antithyroid drugs: what kind of prescription?].

PMID- 24461195
TI  - Nebulized hypertonic saline treatment reduces both rate and duration of
      hospitalization for acute bronchiolitis in infants: an updated meta-analysis.
AB  - Nebulized hypertonic saline (HS) treatment reduced the length of hospitalization
      in infants with acute bronchiolitis in a previous meta-analysis. However, there
      was no reduction in the admission rate. We hypothesized that nebulized HS
      treatment might significantly decrease both the duration and the rate of
      hospitalization if more randomized controlled trials (RCTs) were included. We
      searched MEDLINE, PubMed, CINAHL, and the Cochrane Central Register of Controlled
      Trials (CENTRAL) without a language restriction. A meta-analysis was performed
      based on the efficacy of nebulized HS treatment in infants with acute
      bronchiolitis. We used weighted mean difference (WMD) and risk ratio as effect
      size metrics. Eleven studies were identified that enrolled 1070 infants.
      Nebulized HS treatment significantly decreased the duration and rate of
      hospitalization compared with nebulized normal saline (NS) [duration of
      hospitalization: WMD = -0.96, 95% confidence interval (CI) = -1.38 to -0.54, p <
      0.001; rate of hospitalization: risk ratio = 0.59, 95% CI = 0.37-0.93, p = 0.02].
      Furthermore, nebulized HS treatment had a beneficial effect in reducing the
      clinical severity (CS) score of acute bronchiolitis infants post-treatment (Day
      1: WMD = -0.77, 95% CI = -1.30 to -0.24, p = 0.005; Day 2: WMD = -0.85, 95% CI = 
      1.30 to -0.39, p < 0.001; Day 3: WMD = -1.14, 95% CI = -1.69 to -0.58, p <
      0.001). There was no decrease in the rate of readmission (risk ratio = 1.08, 95%
      CI = 0.68-1.73, p = 0.74). Nebulized HS treatment significantly decreased both
      the rate and the duration of hospitalization. Due to the efficacy and cost
      effectiveness, HS should be considered for the treatment of acute bronchiolitis
      in infants.

PMID- 24461197
TI  - Bone-Conditioned Medium Inhibits Osteogenic and Adipogenic Differentiation of
      Mesenchymal Cells In Vitro.
AB  - BACKGROUND AND PURPOSE: Autografts are used for bone reconstruction in
      regenerative medicine including oral and maxillofacial surgery. Bone grafts
      release paracrine signals that can reach mesenchymal cells at defect sites. The
      impact of the paracrine signals on osteogenic, adipogenic, and chondrogenic
      differentiation of mesenchymal cells has remained unclear. MATERIAL AND METHODS:
      Osteogenesis, adipogenesis, and chondrogenesis were studied with murine ST2
      osteoblast progenitors, 3T3-L1 preadipocytes, and ATDC5 prechondrogenic cells,
      respectively. Primary periodontal fibroblasts from the gingiva, from the
      periodontal ligament, and from bone were also included in the analysis. Cells
      were exposed to bone-conditioned medium (BCM) that was prepared from porcine
      cortical bone chips. RESULTS: BCM inhibited osteogenic and adipogenic
      differentiation of ST2 and 3T3-L1 cells, respectively, as shown by histological
      staining and gene expression. No substantial changes in the expression of
      chondrogenic genes were observed in ATDC5 cells. Primary periodontal fibroblasts
      also showed a robust decrease in alkaline phosphatase and peroxisome proliferator
      activated receptor gamma (PPARgamma) expression when exposed to BCM. BCM also
      increased collagen type 10 expression. Pharmacologic blocking of transforming
      growth factor (TGF)-beta receptor type I kinase with SB431542 and the smad-3
      inhibitor SIS3 at least partially reversed the effect of BCM on PPARgamma and
      collagen type 10 expression. In support of BCM having TGF-beta activity, the
      respective target genes were increasingly expressed in periodontal fibroblasts.
      CONCLUSIONS: The present work is a pioneer study on the paracrine activity of
      bone grafts. The findings suggest that cortical bone chips release soluble
      signals that can modulate differentiation of mesenchymal cells in vitro at least
      partially involving TGF-beta signaling.

PMID- 24461198
TI  - Systematic review with meta-analysis: do interferon lambda 3 polymorphisms
      predict the outcome of interferon-therapy in hepatitis B infection?
AB  - BACKGROUND: Interferon lambda 3 (IFN-lambda3) polymorphisms are the strongest
      genetic predictor of outcome of hepatitis C virus infection and of response to
      Pegylated interferon (PegIFN)-based therapy. Whether this holds true for
      hepatitis B virus (HBV) infection is matter of controversy. AIM: To review the
      association between host genomics and spontaneous or interferon-induced clearance
      of HBV with specific reference to the recently identified interleukin 28B gene
      now renamed IFN-lambda3. METHODS: A literature search was performed on MEDLINE,
      EMBASE and Web of Science for English articles and abstracts using free text
      words and combinations of the following terms 'IL28B', 'IFN lambda', 'genomics',
      'hepatitis B virus', 'interferon' 'GWAS', 'treatment', 'SNPs', 'HLA',
      'polymorphisms'. RESULTS: Genome-wide association studies convincingly
      demonstrated an association between SNPs in the HLA locus and spontaneous
      resolution of HBV infection in subgroups of Asian patients, yet no information is
      available for Caucasians. The preliminary observations of an association between
      IFN-lambda3 SNP and virological and serological responses to IFN in both HBeAg
      positive and -negative patients could not be replicated by subsequent studies.
      Yet, majority of studies performed so far suffer several limitations in terms of
      sample size, selection of the patients, endpoints of therapy, treatment
      strategies and duration of follow-up. CONCLUSIONS: While host genetics is
      associated with an increased likelihood of spontaneous clearance of HBV among
      genotype B/C patients, the relationship between IFN-lambda3 polymorphisms and
      response to IFN has not been confirmed. Further studies in large cohorts of
      homogeneous patients are required, before this genetic test can be recommended in
      clinical practice.

PMID- 24461199
TI  - Familial melanoma by histology and age: joint data from five Nordic countries.
AB  - BACKGROUND: We aimed to estimate lifetime cumulative risk of melanoma (CRM) in
      relatives of patients with melanoma by histology and age at diagnosis in patients
      and relatives. METHODS: A population-based cohort of 238724 first-degree
      relatives of 46091 melanoma patients diagnosed in 1955-2010 in Nordic countries
      was followed for cancer incidence. FINDINGS: The CRM (0-79 years) in first-degree
      relatives of a patient with superficial spreading (SSM), nodular (NM), or lentigo
      maligna melanoma was quite similar, ranging from 2.5% to about 3%, which
      represents about 2-fold increase over the general population risk. When one
      melanoma patient in the family was diagnosed before age 30, the CRM was about 3%.
      When there were > or =2 melanoma patients diagnosed before age 30 in a family,
      CRM for relatives was about 14%, 6% for diagnoses at age 30-59, and 5% for
      diagnoses at age 60 or older. Depending on age at diagnosis of same-sex twins
      (not known whether monozygotic/dizygotic), their CRM was about 7-21%. Although no
      familial case of concordant histological types of acral
      lentiginous/desmoplastic/compound nevus/spindle cell melanomas or malignant blue
      nevus was found, familial risks of discordant histological types of melanoma were
      interchangeably high for most of the types, e.g. higher risk of SSM when a first
      degree relative had NM [standardized incidence ratios (SIR)=2.6, 95% confidence
      interval (CI)=2.1-3.3, n=72] or acral lentiginous (4.0, 95% CI=1.5-8.8, n=6) and
      vice versa. There was a tendency toward concordant age at diagnosis of melanoma
      among relatives of melanoma patients. INTERPRETATION: Findings of this study may
      help clinicians to find subjects at high melanoma risk for the genetic
      counseling. The risk was highest when melanoma occurred in a same-sex twin, one
      first-degree relative diagnosed at young age (<30), or > or =2 first-degree
      relatives. Histological type of melanoma does not seem to play an important role
      in familial melanoma. FUNDING: This work was supported by the Nordic Cancer
      Union, Swedish Council for Working Life and Social Research, and German Cancer
      Aid.

PMID- 24461200
TI  - Cigarette smoking and pancreatic cancer risk: more to the story than just pack
      years.
AB  - PURPOSE: Cigarette smoking is an established risk factor for pancreatic
      adenocarcinoma. However, few studies have thoroughly investigated the effects of
      independent smoking dimensions (duration, intensity, cumulative dose and time
      since quitting) on risk estimates. We analysed data from the Queensland
      Pancreatic Cancer Study (QPCS), an Australian population-based case-control
      study, with the aim of determining which smoking component is primarily important
      to pancreatic cancer risk. METHODS: Our study included 705 pancreatic cancer
      patients and 711 controls. Logistic regression and generalised additive logistic
      regression (for non-linear dose effects) were used to determine odds ratios (ORs)
      and 95% confidence intervals (CIs). RESULTS: Compared to never-smokers, current
      smokers had an increased risk of pancreatic cancer (OR=3.4; 95% CI 2.4-5.0) after
      adjustment for age, sex, education, alcohol intake and birth country. Of the
      various smoking dimensions, smoking duration and time since quitting had a
      greater effect on OR estimates (OR 1.3; 95% CI 1.1-1.4 and OR 0.8; 95% CI 0.7
      0.8) than smoking intensity (OR 1.1; 95% CI 0.9-1.2), once ever-smoking was
      accounted for. CONCLUSIONS: This study confirms the association between cigarette
      smoking and pancreatic adenocarcinoma, and provides evidence to suggest that
      smoking pattern, in addition to dose effect, may affect disease risk.

PMID- 24461201
TI  - Evaluation of long-term antibody responses to two inactivated bovine viral
      diarrhoea virus (BVDV) vaccines.
AB  - The aim of the present study was to determine the serological response of heifers
      after vaccination with two inactivated bovine viral diarrhoea virus (BVDV)
      vaccines by means of various ELISA tests. Three dairy farms were selected from
      the Galicia region of Spain. In each herd, a batch of heifers to be vaccinated
      for the first time was selected and followed for 15 months. Heifers from farm 1
      (n=25) were vaccinated with Vaccine A, whereas heifers from farm 2 (n=16) were
      vaccinated with Vaccine B. Heifers from farm 3 (n=17), where no BVDV vaccines
      were used, acted as controls. Blood samples were analyzed periodically for BVDV
      antibodies, using five commercial ELISAs, based on BVDV p80 antigen or whole
      virus. At the end of the study, none of the animals vaccinated with Vaccine A
      seroconverted according to p80 antibody status, whereas up to 80% tested positive
      by ELISA against whole virus antigen. For the animals vaccinated with Vaccine B,
      2/16 animals seroconverted according to p80 antibody ELISAs, whereas all had
      seroconverted according to the ELISA against whole virus antigen. In most cases,
      based on the use of ELISAs to detect specific antibodies against the p80 protein,
      at 15 months post-vaccination with inactivated BVDV vaccines the responses did
      not seem to interfere with detection of antibody to BVDV infection. However, the
      finding of a small proportion of vaccinated animals seropositive against BVDV p80
      antigen suggests that antibodies that interfere with diagnosis of BVDV infection
      within the herd could exist, even when using p80 ELISAs.

PMID- 24461202
TI  - The immunostimulatory effect of CpG oligodeoxynucleotides on peripheral blood
      mononuclear cells of healthy dogs and dogs with atopic dermatitis.
AB  - Synthetic oligodeoxynucleotides containing cytosine phosphatidyl guanine-rich DNA
      sequences (CpG ODN) can promote T-helper type 1 (Th1) responses, reduce T-helper
      type 2 (Th2) responses and/or favour regulatory T cell (Treg) responses in vitro
      and in vivo in humans and animals, by acting via Toll-like receptor 9 (TLR9).
      Since CpG ODN can be used as immune-modulators for canine atopic dermatitis (AD),
      the aim of the current study was to investigate their immunostimulatory potential
      on peripheral blood mononuclear cells (PBMC) and their subsets, from AD and
      healthy dogs. Expression of TLR9 and cytokine mRNA in CpG ODN-stimulated and
      unstimulated cells was assessed by real-time quantitative PCR. Stimulation of
      PBMC with CpG class C ODN upregulated mRNA expression of interleukin (IL)-6,
      interferon (IFN)-gamma and IL-12p40 in AD dogs (P<0.05). It also stimulated IFN
      gamma protein secretion by PBMC of atopic and healthy dogs as measured by ELISA.
      In healthy dogs only, CpG class C ODN stimulated IFN-alpha mRNA production by
      CD21(+) cells, and IL-10, IL-13 and IFN-gamma mRNA production by CD3(+) cells.
      Increased expression of TLR9 mRNA was only observed in CD3(+) cells from AD dogs.
      No significantly increased gene expression was found in the CD11c(+) subset upon
      stimulation, for those genes evaluated. The results indicate that PBMC of healthy
      and atopic dogs are sensitive to stimulation with CpG ODN class C, with a
      resulting Th1 cytokine response in AD dogs and a mixed Th1/Th2/Treg cytokine
      response in healthy dogs. From this study, little evidence was found to support
      the use of CpG ODN class C for therapeutic purposes in dogs affected with AD.

PMID- 24461203
TI  - Relevance of ovarian follicular development to the seasonal impairment of
      fertility in weaned sows.
AB  - A field study was conducted to estimate seasonal differences in follicular
      development in weaned sows and to evaluate the implication of these differences
      on seasonal infertility. A total of 110 sows were selected at weaning during
      winter-spring (WS, n=58) and summer-autumn (SA, n=52). Ovaries were scanned once
      daily from weaning to the onset of oestrus and twice daily from then until
      ovulation. Six sows during WS were removed from study for not showing growing
      follicles at weaning. Oestrus was evaluated twice daily from day 1 after weaning
      to day 14 post-weaning. One of 52 (1.9%) sows in WS and 9/52 (17.3%) in SA showed
      no signs of oestrus within 14 days of weaning (P<0.05). The diameters of the
      follicles at weaning, at the onset of oestrus and just before ovulation were
      smaller (P<0.01) in SA sows than in WS sows. There were fewer follicles in SA
      sows than in WS sows just before ovulation (P<0.05). Fifty of 51 (98.0%) sows in
      WS and 31/43 (72.1%) sows in SA experienced a weaning-to-oestrus interval (WOI)
      of 3-6 days (P<0.05). Fifty-one of 52 (98.1%) sows in WS and 43/52 (82.7%) sows
      in SA were inseminated; the percentage of pregnant sows that failed to farrow was
      lower in WS (1/51, 2.0%) than in SA (5/43, 11.6%; P<0.05). The percentage of
      farrowed sows was greater in WS (46/51, 90.2%) than in SA (32/43, 74.4%; P<0.05).
      Sows in WS had on average 1.5 more piglets than sows in SA (P<0.05). Sows with a
      WOI of 3-6 days had lower rates of pregnancy losses (P<0.05) and higher farrowing
      percentages (P<0.01) than those with a WOI>6 days, irrespective of season.

PMID- 24461204
TI  - A new dried milk sampling technique and its application for progesterone
      detection in cows.
AB  - A new method for milk sample collection and storage, based on a dried milk
      sampling technique, is proposed. The method includes application of a whole milk
      sample to a porous membrane followed by drying. One hundred whole milk samples
      (dried and liquid) taken on day 21 post insemination were analysed for
      progesterone by ELISA and results for both dried and liquid samples were well
      correlated (r=0.911). Milk progesterone ELISA accuracy for pregnancy diagnosis in
      cows was 87%. 

PMID- 24461205
TI  - Longevity in pet dogs: understanding what's missing.

PMID- 24461206
TI  - Availability and characteristics of abortion training in US ob-gyn residency
      programs: a national survey.
AB  - OBJECTIVE: To assess the availability and characteristics of abortion training in
      US ob-gyn residency programs. METHODS: We surveyed fourth-year residents at US
      residency programs by email regarding availability and type of abortion training,
      procedural experience and self-assessed competence in abortion skills. We
      conducted multivariable, ordinal logistic regression with general estimating
      equations to determine individual-level and resident-reported, program-level
      correlates of quantity of uterine evacuation procedures done during residency.
      RESULTS: Three hundred sixty-two residents provided data, representing 161 of the
      240 residency programs contacted. Access to training in elective abortion was
      available to most respondents: 54% reported routine training--where abortion
      training was routinely scheduled; 30% reported opt-in training--where training
      was available but not routinely integrated; and 16% reported that elective
      abortion training was not available. Residents in programs with routine elective
      abortion training and those who intended to do abortions before residency did a
      greater number of first-trimester manual uterine aspiration and second-trimester
      dilation and evacuation procedures than those without routine training.
      Similarly, routine, integrated training, even for indications other than elective
      abortion, correlated with more clinical experience (all p<.01, odds ratio and
      confidence interval shown below). CONCLUSION: There is a strong independent
      relationship between routine training and greater clinical experience with
      uterine aspiration procedures.

PMID- 24461207
TI  - Metastatic castration-resistant prostate cancer. Part 1: the challenges of the
      disease and its treatment.
AB  - Prostate cancer is the most commonly occurring solid tumour in men and the second
      highest cause of cancer deaths. For early stage disease surgery and/or radiation
      is often curative, and for locally advanced or metastatic disease initial
      treatment involves removing the drive to tumour growth provided by androgens, via
      androgen deprivation therapy. In the majority, this treatment eventually fails
      and castration-resistant prostate cancer (CRPC) develops - a condition with
      usually a poor prognosis and significant impact on quality of life. For many
      years mitoxantrone was the only chemotherapy for CRPC, but it had only a
      palliative effect with no effect on survival. This was followed by docetaxel -
      the first agent to show an increase in overall survival in metastatic CRPC.
      Recently, newer agents with different modes of action have been developed. These
      include the novel taxane, cabazitaxel (which has shown superiority to docetaxel),
      abiraterone (an anti-androgen), alpharadin (a radionucleotide), sipuleucel-T (a
      cellular immunotherapy product) and enzalutamide (an androgen receptor blocker),
      all of which are superior to placebo. This article reviews CRPC and the results
      of studies with these agents. 

PMID- 24461208
TI  - Metastatic castration-resistant prostate cancer. Part 2: helping patients make
      informed choices and managing treatment side effects.
AB  - Nursing patients with mCRPC presents considerable challenges to nurses. They need
      to draw upon a variety of skills to support and care for patients throughout the
      disease journey. As the majority of patients with mCRPC are elderly, they tend to
      have co-morbidities and possibly side effects from previous treatment that need
      consideration. Some patients will present at around 50 years of age and will also
      have specific, different needs. The majority of patients with mCRPC will have
      bone metastases that may cause disability and pain. The International Society of
      Geriatric Oncology (SIOG) has recommended that older men are treated according to
      health status and not chronological age. So nurses need to understand how to
      assess patients' status effectively, regardless of their age. This will enable
      nurses to provide appropriate and effective intervention and to support their
      patients during treatment for advancing disease. This article reviews the main
      methods of assessment and the nursing interventions for the common side effects
      associated with treatment for mCRPC. 

PMID- 24461209
TI  - Restrictive and dynamic conceptions of the unconscious: perspectives from moral
      and developmental psychology.
AB  - Newell & Shanks' (N&S's) conceptualization of the unconscious is overly
      restrictive, compared to standard social psychological accounts. The dichotomy
      between distal and proximal cues is a weak point in their argument and does not
      circumvent the existence of unconscious influences on decision making. Evidence
      from moral and developmental psychology indicates that decision making results
      from a dynamic mixture of conscious and unconscious processes. 

PMID- 24461210
TI  - Molecular detection and characterization of Cryptosporidium species in household
      dogs, pet shop puppies, and dogs kept in a school of veterinary nursing in Japan.
AB  - Members of Cryptosporidium species, which are protozoan parasites, are prevalent
      worldwide and can cause diarrhoea in both humans and animals, including dogs. In
      addition, the Cryptosporidium species harboured in dogs have the potential for
      zoonotic transmission. The purpose of the present study was to determine the
      prevalence of Cryptosporidium species infection and perform molecular
      characterization of isolates in household dogs, pet shop puppies, and dogs kept
      in a school of veterinary nursing in Japan. Fresh faecal samples were collected
      once from 529 household dogs (aged from 2 months to 18 years old, from 9
      veterinary clinics located in 6 different regions), 471 pet shop puppies (<= 3
      months old, from 4 pet shops located in 2 different regions), and 98 dogs (aged
      from 2 to 11 years old) kept in a veterinary nursing school. A nested polymerase
      chain reaction (PCR) assay targeting the 18S rRNA gene was employed for the
      detection of Cryptosporidium species, and 111 random samples of PCR amplicons
      (approximately 500-bp) were sequenced for the molecular characterization of the
      isolates. The prevalences of Cryptosporidium species in household dogs, pet shop
      puppies, and veterinary nursing school dogs were 7.2%, 31.6%, and 18.4%,
      respectively. In household dogs, no significant correlation was observed between
      the prevalence of Cryptosporidium species and the age (<= 6 months vs. >6
      months), living conditions (indoor vs. outdoor), faecal conditions (formed vs.
      unformed), and location of residence. In pet shop puppies, the prevalence of
      Cryptosporidium species was not related to faecal condition; however, the
      prevalence significantly differed among the pet shops. All of the 111 sequence
      samples (26 from household dogs, 75 from pet shop puppies, and 10 from veterinary
      nursing school dogs) were identified as Cryptosporidium canis. The present study
      demonstrates a high prevalence of Cryptosporidium species infections in pet shop
      puppies and dogs of a veterinary nursing school in Japan. However, because
      Cryptosporidium hominis and Cryptosporidium parvum are the most common causes of
      human infections, it is likely that the risk of zoonotic transmission of
      Cryptosporidium species from dogs to humans is low.

PMID- 24461211
TI  - Disclosing medical errors: the view from the USA.
AB  - BACKGROUND: Disclosure is increasingly seen as a key component of efforts to
      improve safety, but does not yet reliably occur in all organizations in the U.S.
      APPROACH: We describe the experience to date with disclosure in the U.S. and
      illustrate the issues with specific clinical examples. Both reputational and
      legal concerns represent substantial barriers. The evidence to date-mostly from
      single sites - shows that not only is disclosure the right thing to do, it also
      appears to decrease malpractice risk. We also discuss the related issue of
      compensation-practices around this vary greatly. Underlying the push for greater
      disclosure is also the belief that better disclosure results in an improved
      culture of safety, which in turn may improve the quality and safety of care.
      CONCLUSIONS: Providers have an ethical imperative to disclosure error to
      patients, and the limited available evidence shows that doing so actually
      decreases malpractice risk. While disclosure is not yet routine practice in the
      U.S., the approach is clearly gaining momentum. Telling patients what happened is
      not enough. They also deserve an apology, and if harmed, to be made whole
      emotionally and financially. Greater disclosure may not only help individual
      patients, but may also help with improving safety overall.

PMID- 24461212
TI  - A framework to analyze hospital-wide patient flow logistics: evidence from an
      Italian comparative study.
AB  - Through a comparative study of six Italian hospitals, the paper develops and
      tests a framework to analyze hospital-wide patient flow performance. The
      framework adopts a system-wide approach to patient flow management and is
      structured around three different levels: (1) the hospital, (2) the pipelines
      (possible patient journeys within the hospital) and (3) the production units
      (physical spaces, such as operating rooms, where service delivery takes places).
      The focus groups and the data analysis conducted within the study support that
      the model is a useful tool to investigate hospital-wide implications of patient
      flows. The paper provides also evidence about the causes of hospital patient flow
      problems. Particularly, while shortage of capacity does not seem to be a relevant
      driver, our data shows that patient flow variability caused by inadequate
      allocation of capacity does represent a key problem. Results also show that the
      lack of coordination between different pipelines and production units is
      critical. Finally, the problem of overlapping between elective and unscheduled
      cases can be solved by setting aside a certain level of capacity for unexpected
      peaks. 

PMID- 24461213
TI  - The public gets what the public wants: experiences of public reporting in long
      term care in Europe.
AB  - INTRODUCTION: Public reporting of quality in long-term care is advocated on the
      basis of allowing providers to improve their performance by benchmarking and
      supporting users to choose the best providers. Both mechanisms are intended to
      drive improvements in quality. However, there is relatively scarce comparative
      research on the experiences and impact of public reporting on quality in long
      term care in Europe. METHODS: Using information gathered from key informants by
      means of a structured questionnaire and country profiles, this paper discusses
      experiences with public reporting mechanisms in seven European countries and
      available information on their impact on quality in long-term care. RESULTS:
      Countries surveyed included a variety of public reporting schemes, ranging from
      pilot programmes to statutory mechanisms. Public reporting mechanisms more often
      focus on institutional care. Inspections carried out as part of a legal quality
      assurance framework are the main source of information gathering, supplemented by
      provider self-assessments in the context of internal quality management and user
      satisfaction surveys. Information on quality goes well beyond structural
      indicators to also include indicators on quality of life of users. Information is
      displayed using numerical scores (percentages), but also measures such as ratings
      (similar to school grades) and ticks and crosses. Only one country corrects for
      case-mix. The internet is the preferred medium of displaying information.
      DISCUSSION: There was little evidence to show whether public reporting has a
      significant impact on driving users' choices of provider. Studies reported low
      awareness of quality indicators among potential end users and information was not
      always displayed in a convenient format, e.g. through complicated numerical
      scores. There is scarce evidence of public reporting directly causing improved
      quality, although the relative youth and the pilot characteristics of some of the
      schemes covered here could also have contributed to downplay their impact. The
      establishment of public reporting mechanisms did however contribute to shaping
      the discussion on quality measurement in several of the countries surveyed.
      CONCLUSIONS: The findings presented in this paper highlight the need to consider
      some factors in the discussion of the impact of public reporting in long-term
      care, namely, the organisation of care markets, frequently characterised by
      limited competition; the circumstances under which user choice takes place, often
      made under conditions of duress; and the leadership conditions needed to bring
      about improvements in quality in different care settings.

PMID- 24461214
TI  - Unconscious influences on decision making: a critical review.
AB  - To what extent do we know our own minds when making decisions? Variants of this
      question have preoccupied researchers in a wide range of domains, from mainstream
      experimental psychology (cognition, perception, social behavior) to cognitive
      neuroscience and behavioral economics. A pervasive view places a heavy
      explanatory burden on an intelligent cognitive unconscious, with many theories
      assigning causally effective roles to unconscious influences. This article
      presents a novel framework for evaluating these claims and reviews evidence from
      three major bodies of research in which unconscious factors have been studied:
      multiple-cue judgment, deliberation without attention, and decisions under
      uncertainty. Studies of priming (subliminal and primes-to-behavior) and the role
      of awareness in movement and perception (e.g., timing of willed actions,
      blindsight) are also given brief consideration. The review highlights that
      inadequate procedures for assessing awareness, failures to consider artifactual
      explanations of "landmark" results, and a tendency to uncritically accept
      conclusions that fit with our intuitions have all contributed to unconscious
      influences being ascribed inflated and erroneous explanatory power in theories of
      decision making. The review concludes by recommending that future research should
      focus on tasks in which participants' attention is diverted away from the
      experimenter's hypothesis, rather than the highly reflective tasks that are
      currently often employed. 

PMID- 24461215
TI  - ROVER variant caller: read-pair overlap considerate variant-calling software
      applied to PCR-based massively parallel sequencing datasets.
AB  - BACKGROUND: We recently described Hi-Plex, a highly multiplexed PCR-based target
      enrichment system for massively parallel sequencing (MPS), which allows the
      uniform definition of library size so that subsequent paired-end sequencing can
      achieve complete overlap of read pairs. Variant calling from Hi-Plex-derived
      datasets can thus rely on the identification of variants appearing in both reads
      of read-pairs, permitting stringent filtering of sequencing chemistry-induced
      errors. These principles underly ROVER software (derived from Read Overlap PCR
      MPS variant caller), which we have recently used to report the screening for
      genetic mutations in the breast cancer predisposition gene PALB2. Here, we
      describe the algorithms underlying ROVER and its usage. RESULTS: ROVER enables
      users to quickly and accurately identify genetic variants from PCR-targeted,
      overlapping paired-end MPS datasets. The open-source availability of the software
      and threshold tailorability enables broad access for a range of PCR-MPS users.
      METHODS: ROVER is implemented in Python and runs on all popular POSIX-like
      operating systems (Linux, OS X). The software accepts a tab-delimited text file
      listing the coordinates of the target-specific primers used for targeted
      enrichment based on a specified genome-build. It also accepts aligned sequence
      files resulting from mapping to the same genome-build. ROVER identifies the
      amplicon a given read-pair represents and removes the primer sequences by using
      the mapping co-ordinates and primer co-ordinates. It considers overlapping read
      pairs with respect to primer-intervening sequence. Only when a variant is
      observed in both reads of a read-pair does the signal contribute to a tally of
      read-pairs containing or not containing the variant. A user-defined threshold
      informs the minimum number of, and proportion of, read-pairs a variant must be
      observed in for a 'call' to be made. ROVER also reports the depth of coverage
      across amplicons to facilitate the identification of any regions that may require
      further screening. CONCLUSIONS: ROVER can facilitate rapid and accurate genetic
      variant calling for a broad range of PCR-MPS users.

PMID- 24461216
TI  - Culturally determined risk factors for postnatal depression in Sub-Saharan
      Africa: a mixed method systematic review.
AB  - BACKGROUND: Research suggests that African women experience postnatal depression
      (PND) at a similar rate to that reported in developed countries. If PND is to be
      better understood in African populations, its risk factors need to be reliably
      identified. Studies in the developing world have found that risk factors are
      often culturally determined. This review aimed at improving our understanding of
      the culturally determined risk factors of PND within Sub-Saharan Africa by
      integrating evidence from quantitative and qualitative studies. METHODS: A mixed
      method systematic review was employed. Nine quantitative and three qualitative
      studies were quality assessed, synthesised, and integrated. RESULTS: Quantitative
      studies indicated that stressful life events, cultural values and the African
      extended family system have an influential role in women's experience of PND.
      Qualitative studies described the impact of negative cultural perceptions of
      others and adhering to cultural traditions and values as contributing to the
      development and maintenance of PND. LIMITATIONS: The small number of studies is a
      limitation within the available body of research. Search strategies only included
      English language articles. CONCLUSIONS: Although some risk factors for postnatal
      depression were similar to those identified in studies in developed countries,
      important differences exist; most notably the influence of traditional African
      value systems, customs and antenatal exposure to extreme societal stress. The
      findings of this review are especially important for the development of a
      predictive model for PND within Sub-Saharan Africa and when working with migrant
      Sub-Saharan African mothers.

PMID- 24461217
TI  - Process improvement in surgery.

PMID- 24461219
TI  - The past and future of the generalist general surgeon.

PMID- 24461221
TI  - Implementation of a novel night float call system: resident satisfaction and
      quality of life.
AB  - BACKGROUND: Compliance with Professional Association of Internes and Residents of
      Ontario duty hour guidelines has been problematic at our institution. To
      facilitate orthopedic residents' ability to go home postcall without significant
      disruption of ongoing clinical activities, a novel call system was adopted at our
      tertiary care centre. We sought to evaluate the satisfaction and quality of life
      of orthopaedic residents with that system. METHODS: We administered
      questionnaires to on-service residents. These included the Short Form-36
      questionnaire and others addressing topics including education, stress, work
      related problems and miscellaneous concerns. RESULTS: Seventeen residents were
      surveyed: 6 who had just completed a night float rotation, and 11 who were on a
      regular orthopedic service rotation while the night float system was in place.
      Quality of life was similar between residents on the night float block and those
      on the standard rotation; it was also similar to age-matched Canadian normative
      data. Eighty-nine percent of residents agreed that the presence of the night
      float rotation improved their quality of life on standard rotations, and 100%
      felt that their education was improved on standard rotations by having the night
      float system in place. CONCLUSION: This call system results in improved resident
      quality of life and widespread overall satisfaction, and may be considered as a
      viable alternative to traditional call formats. Follow-up data as more residents
      experience the night float block will be valuable.

PMID- 24461220
TI  - Development of an orthopedic surgery trauma patient handover checklist.
AB  - BACKGROUND: In surgery, preoperative handover of surgical trauma patients is a
      process that must be made as safe as possible. We sought to determine vital
      clinical information to be transferred between patient care teams and to develop
      a standardized handover checklist. METHODS: We conducted standardized small-group
      interviews about trauma patient handover. Based on this information, we created a
      questionnaire to gather perspectives from all Canadian Orthopaedic Association
      (COA) members about which topics they felt would be most important on a handover
      checklist. We analyzed the responses to develop a standardized handover
      checklist. RESULTS: Of the 1106 COA members, 247 responded to the questionnaire.
      The top 7 topics felt to be most important for achieving patient safety in the
      handover were comorbidities, diagnosis, readiness for the operating room,
      stability, associated injuries, history/mechanism of injury and outstanding
      issues. The expert recommendations were to have handover completed the same way
      every day, all appropriate radiographs available, adequate time, all appropriate
      laboratory work and more time to spend with patients with more severe illness.
      CONCLUSION: Our main recommendations for safe handover are to use standardized
      checklists specific to the patient and site needs. We provide an example of a
      standardized checklist that should be used for preoperative handovers. To our
      knowledge, this is the first checklist for handover developed by a group of
      experts in orthopedic surgery, which is both manageable in length and simple to
      use.

PMID- 24461222
TI  - Cephalic vein cutdown for totally implantable central venous port in children: a
      retrospective analysis of prospectively collected data.
AB  - BACKGROUND: The jugular vein cutdown for a totally implantable central venous
      port (TICVP) has 2 disadvantages: 2 separate incisions are needed and the risk
      for multiple vein occlusions. We sought to evaluate the feasibility of a cephalic
      vein (CV) cutdown in children. METHODS: We prospectively followed patients who
      underwent a venous cutdown for implantation of a TICVP between Jan. 1, 2002, and
      Dec. 31, 2006. For patients younger than 8 months, an external jugular vein
      cutdown was initially tried without attempting a CV cutdown. For patients older
      than 8 months, a CV cutdown was tried initially. We recorded information on age,
      weight, outcome of the CV cutdown and complications. RESULTS: During the study
      period, 143 patients underwent a venous cutdown for implantation of a TICVP: 25
      younger and 118 older than 8 months. The CV cutdown was successful in 73 of 118
      trials. The 25th percentile and median body weight for 73 successful cases were
      15.4 kg and 28.3 kg, respectively. There was a significant difference in the
      success rate using the criterion of 15 kg as the cutoff. The overall complication
      rate was 8.2%. CONCLUSION: The CV cutdown was an acceptable procedure for TICVP
      in children. It could be preferentially considered for patients weighing more
      than 15 kg who require TICVP.

PMID- 24461223
TI  - Adherence to adjuvant endocrine therapy in estrogen receptor-positive breast
      cancer patients with regular follow-up.
AB  - BACKGROUND: Adjuvant hormonal therapy is crucial in the treatment of estrogen
      receptor-positive breast cancer. The nonadherence rate to hormonal treatment is
      reported to be as high as 60%. The goal of this study was to evaluate the factors
      evoked by the patients as well as the demographic and disease-related factors
      that could be associated with nonadherence to adjuvant hormonal therapy. METHODS:
      All consecutive patients treated for an estrogen receptor-positive breast cancer
      who showed up for regular follow-up with a single breast specialist between
      November 2008 and April 2009 were included in the study. We assessed adherence to
      hormonal therapy (either with tamoxifen or aromatase inhibitor). Reasons for
      adherence and nonadherence were collected. Records were also reviewed for
      demographic and cancer characteristics and for treatment components. RESULTS: We
      included 161 patients in the study; 150 (93.2%) adhered to hormonal treatment.
      Side effects and absence of conviction were the main reasons for nonadherence.
      The importance of the diagnosis of cancer, fear of recurrence and regular follow
      up were reported as the main reasons for adherence. CONCLUSION: Severity of
      disease and side effects are associated with nonadherence to treatment. Strict
      follow-up appears to be a necessary adjunct in the adherence to treatment. The
      association between demographic and cancer characteristics and treatment
      components needs further investigation. However, these factors may help identify
      patients at risk of nonadherence and help the oncology team.

PMID- 24461224
TI  - Prioritization and willingness to pay for bariatric surgery: the patient
      perspective.
AB  - BACKGROUND: Access to publicly funded bariatric surgery is limited, potential
      candidates face lengthy waits, and no universally accepted prioritization
      criteria exist. We examined patients' perspectives regarding prioritization for
      surgery. METHODS: We surveyed consecutively recruited patients awaiting bariatric
      surgery about 9 hypothetical scenarios describing patients waiting for surgery.
      Respondents were asked to rank the priority of these hypothetical patients on the
      wait list relative to their own. Scenarios examined variations in age, clinical
      severity, functional impairment, social dependence and socioeconomic status.
      Willingness to pay for faster access was assessed using a 5-point ordinal scale
      and analyzed using multivariable logistic regression. RESULTS: The 99 respondents
      had mean age of 44.7 +/- 9.9 years, 76% were women, and the mean body mass index
      was 47.3 +/- SD 7.6. The mean wait for surgery was 34.4 +/- 9.4 months.
      Respondents assigned similar priority to hypothetical patients with
      characteristics identical to theirs (p = 0.22) and higher priority (greater
      urgency) to those exhibiting greater clinical severity (p < 0.001) and functional
      impairment (p = 0.003). Lower priority was assigned to patients at the extremes
      of age (p = 0.006), on social assistance (p < 0.001) and of high socioeconomic
      status (p < 0.001). Most (85%) respondents disagreed with payment to expedite
      access, although participants earning more than $80 000/year were less likely to
      disagree. CONCLUSION: Most patients waiting for bariatric surgery consider
      greater clinical severity and functional impairments related to obesity to be
      important prioritization indicators and disagreed with paying for faster access.
      These findings may help inform future efforts to develop acceptable
      prioritization strategies for publicly funded bariatric surgery.

PMID- 24461225
TI  - A comparison of surgical delays in directly admitted versus transferred patients
      with hip fractures: opportunities for improvement?
AB  - BACKGROUND: The increasing incidence of hip fractures in our aging population
      challenges orthopedic surgeons and hospital administrators to effectively care
      for these patients. Many patients present to regional hospitals and are
      transferred to tertiary care centres for surgical management, resulting in long
      delays to surgery. Providing timely care may improve outcomes, as delay carries
      an increased risk of morbidity and mortality. METHODS: We retrospectively
      reviewed the cases of all patients with hip fractures treated in a single Level 1
      trauma centre in Canada between 2005 and 2012. We compared quality indicators and
      outcomes between patients transferred from a peripheral hospital and those
      directly admitted to the trauma centre. RESULTS: Of the 1191 patients
      retrospectively reviewed, 890 met our inclusion criteria: 175 who were
      transferred and 715 admitted directly to the trauma centre. Transfer patients'
      median delay from admission to operation was 93 hours, whereas nontransfer
      patients waited 44 hours (p < 0.001). The delay predominantly occurred before
      transfer, as the patients had to wait for a bed to become available at the trauma
      centre. The median length of stay in hospital was 20 days for transfer patients
      compared with 13 days for nontransfer patients (p < 0.001). Regional policy
      changes enacted in 2011 decreased the median transfer delay from regional
      hospital to tertiary care centre from 47 to 27 hours (p = 0.005). CONCLUSION:
      Policy changes can have a significant impact on patient care. Prioritizing
      patients and expediting transfer will decrease overall mortality, reduce hospital
      stay and reduce the cost of hip fracture care.

PMID- 24461226
TI  - Viability assessment of the chondral flap in patients with cam-type
      femoroacetabular impingement: a preliminary report.
AB  - BACKGROUND: Delaminated acetabular cartilage is a common finding in patients
      undergoing surgical dislocation or hip arthroscopy in the treatment of cam-type
      femoroacetabular impingement. Current treatment involves resection of the free
      cartilage flap with or without acetabular rim trimming. The viability of the
      delaminated cartilage flap is not known. We sought to examine if the acetabular
      cartilage still has viable cartilage cells and, if so, what type of cartilage is
      present. METHODS: We examined the delaminated cartilage flaps from patients
      undergoing surgical dislocation and osteochondroplasty for symptomatic cam-type
      impingement. We performed hematoxylin and eosin staining and histological
      analysis using light microscopy to determine cartilage viability and cartilage
      type. RESULTS: We examined 12 delaminated cartilage flaps from 11 patients (10
      men, 1 woman, average age 30.1 yr). Ninety percent chondrocyte viability was
      confirmed in 11 of 12 flaps. Six of 12 flaps were composed predominantly of
      hyaline cartilage, 4 were a mixed population of fibrocartilage and hyaline
      cartilage and 2 were predominantly fibrocartilage. CONCLUSION: Our findings
      suggest that the delaminated cartilage flap in patients with femoroacetabular
      impingement may retain a large amount of viable chondrocytes. Development of
      surgical techniques focusing on refixation of this flap as an alternative to
      excision and microfracture should be considered.

PMID- 24461228
TI  - Identification and characterization of omega-amidase as an enzyme metabolically
      linked to asparagine transamination in Arabidopsis.
AB  - In higher plants, asparagine (Asn) is a major form of organic nitrogen used for
      transport and storage. There are two pathways of Asn metabolism, involving
      asparaginase and Asn aminotransferase. The enzyme serine:glyoxylate
      aminotransferase encoded by AGT1 has been identified as an asparagine
      aminotransferase in Arabidopsis. The product of asparagine transamination, alpha
      ketosuccinamate, can be hydrolyzed by the enzyme omega-amidase to form
      oxaloacetate and ammonia. A candidate gene was identified in Arabidopsis based on
      its sequence similarity with mouse omega-amidase. Recombinant omega-amidase
      exhibited comparable catalytic activities with alpha-hydroxysuccinamate, alpha
      ketosuccinamate and alpha-ketoglutaramate, the product of glutamine
      transamination. A mutant with a T-DNA inserted in the first exon accumulated
      alpha-ketosuccinamate and alpha-hydroxysuccinamate as compared with wild-type,
      both under control conditions and after treatment with Asn. Treatment with Asn
      led to decreased transcript levels of omega-amidase in root, while transcript
      levels of AGT1 are increased under these conditions, suggesting that excess Asn
      may lead to the accumulation of alpha-ketosuccinamate and alpha
      hydroxysuccinamate. 

PMID- 24461227
TI  - Retrospective review of injury severity, interventions and outcomes among
      helicopter and nonhelicopter transport patients at a Level 1 urban trauma centre.
AB  - BACKGROUND: Air ambulance transport for injured patients is vitally important
      given increasing patient volumes, the limited number of trauma centres and
      inadequate subspecialty coverage in nontrauma hospitals. Air ambulance services
      have been shown to improve patient outcomes compared with ground transport in
      select circumstances. Our primary goal was to compare injuries, interventions and
      outcomes in patients transported by helicopter versus nonhelicopter transport.
      METHODS: We performed a retrospective 10-year review of 14 440 patients
      transported to an urban Level 1 trauma centre by helicopter or by other means. We
      compared injury severity, interventions and mortality between the groups.
      RESULTS: Patients transported by helicopter had higher median injury severity
      scores (ISS), regardless of penetrating or blunt injury, and were more likely to
      have Glasgow Coma Scale scores less than 8, require airway control, receive blood
      transfusions and require admission to the intensive care unit or operating room
      than patients transported by other means. Helicopter transport was associated
      with reduced overall mortality (odds ratio 0.41, 95% confidence interval 0.33
      0.39). Patients transported by other methods were more likely to die in the
      emergency department. The mean ISS, regardless of transport method, rose from
      12.3 to 15.1 (p = 0.011) during our study period. CONCLUSION: Patients
      transported by helicopter to an urban trauma centre were more severely injured,
      required more interventions and had improved survival than those arriving by
      other means of transport.

PMID- 24461229
TI  - A 1-Year Prospective Clinical and Radiographic Study of Early-Loaded Bone Level
      Implants in the Posterior Maxilla.
AB  - PURPOSES: The primary aim of the study was to investigate a 1-year success rate
      of early-loaded bone level implants with a chemically modified sand-blasted,
      large grit, acid-etched surface (SLActive(r), Institut Straumann AG, Basel,
      Switzerland) in the posterior maxilla. Secondary objectives included stability of
      these implants and peri-implant bone level. MATERIALS AND METHODS: Bone level(r)
      implants (Institut Straumann AG) inserted into premolar and/or molar maxillary
      sites were loaded after 6 weeks of healing. The implants were monitored for 1
      year using the following outcome measures: implant success, primary and secondary
      stability, and peri-implant bone level. RESULTS: Out of 37 implants placed in 13
      patients, 36 reached sufficient stability and were early loaded, whereas one
      underwent a delayed loading protocol. One-year success rate of early-loaded
      implants was 100%. Implant stability at baseline was 71.7 +/- 5. 6 to be steadily
      increased thereafter up to 1 year (80.3 +/- 3.3), except at 2 weeks when a
      nonsignificant decrease was noticed (71.9 +/- 3.9). Continuous and significant
      bone loss was observed, reaching 0.4 +/- 0.1 mm in the first postoperative year.
      CONCLUSION: Bone level implants with the SLActive surface placed into low-density
      bone and loaded after 6 weeks of healing can predictably achieve and maintain a
      successful tissue integration.

PMID- 24461230
TI  - Orthopedics coding and funding.
AB  - The French tarification a l'activite (T2A) prospective payment system is a
      financial system in which a health-care institution's resources are based on
      performed activity. Activity is described via the PMSI medical information system
      (programme de medicalisation du systeme d'information). The PMSI classifies
      hospital cases by clinical and economic categories known as diagnosis-related
      groups (DRG), each with an associated price tag. Coding a hospital case involves
      giving as realistic a description as possible so as to categorize it in the right
      DRG and thus ensure appropriate payment. For this, it is essential to understand
      what determines the pricing of inpatient stay: namely, the code for the surgical
      procedure, the patient's principal diagnosis (reason for admission), codes for
      comorbidities (everything that adds to management burden), and the management of
      the length of inpatient stay. The PMSI is used to analyze the institution's
      activity and dynamism: change on previous year, relation to target, and
      comparison with competing institutions based on indicators such as the mean
      length of stay performance indicator (MLS PI). The T2A system improves overall
      care efficiency. Quality of care, however, is not presently taken account of in
      the payment made to the institution, as there are no indicators for this; work
      needs to be done on this topic. 

PMID- 24461231
TI  - Post-traumatic osteoarthritis of the elbow.
AB  - Post-traumatic osteoarthritis of the elbow is an uncommon condition in which the
      clinical manifestations are often at variance with the radiological findings. In
      symptomatic forms, pain and stiffness are variably combined. When non-operative
      management fails, the decision to perform surgery is taken on a case-by-case
      basis depending on age, activity level, patient discomfort, and osteoarthritis
      location and severity as assessed by CT scan arthrography. Elbow instability or
      subluxation should be sought. Post-traumatic elbow osteoarthritis raises
      difficult therapeutic problems in young patients. The goal of treatment is to
      obtain a low level of pain with sufficient motion range to ensure good function,
      while preserving future surgical options and delaying elbow arthroplasty to the
      extent possible. 

PMID- 24461232
TI  - Arthrosis of the knee in chronic anterior laxity.
AB  - Arthrosis following rupture of the anterior cruciate ligament has been analysed
      in two series. The first series was derived from a review of 150 cases of
      reconstruction of the anterior cruciate ligament with a follow-up of 3 years or
      more. Arthrosis was seen to have developed in 13.3%. The second series was
      concerned with 64 cases of unilateral arthrosis treated by upper tibial valgus
      osteotomy in whom there had been a previous rupture of the anterior cruciate
      ligament. The 'tolerance interval'--that is the time between the original
      ligamentous injury and the time of osteotomy--for the development of arthrosis
      was very variable, ranging in the natural-history cases from 10 to 50 years, with
      a mean of 35 years. It is important to recognise the radiological signs of the
      onset of arthrosis. These are osteophytosis of the intercondylar notch,
      osteophyte formation at the posterior part of the medial tibial plateau, and, in
      particular, narrowing of the medial joint line with posterior subluxation of the
      medial femoral condyle, well seen in lateral radiographs whilst standing on one
      lower limb. Early arthroses, appearing after 10 years, may occur as a 'natural
      arthrosis', but it develops much more frequently after surgical treatment that
      had failed to correct anterior laxity and particularly when it had been performed
      on knees that were already pre-arthrotic. The main factor in arthrosis is
      anterior laxity measured radiologically by an 'active Lachman' radiograph.
      Removal of the medial meniscus which in itself, is liable to produce arthrosis,
      is even more harmful in anterior cruciate laxity since it doubles the degree of
      anterior subluxation of the tibia seen on unilateral weight-bearing. The
      development of varus deformity, which characterises progressive arthrosis, has
      its origin in wear of the posterior part of the medial tibial plateau caused by
      anterior cruciate laxity. Other factors play an important part such as associated
      lateral laxity, constitutional genu varum and weakness of the hamstring muscles,
      which oppose the subluxating action of the quadriceps.

PMID- 24461233
TI  - Post-traumatic carpal instability.
AB  - The complexity of the carpus explains the difficulty treating carpal injuries.
      Lesions are dominated by perilunate dislocation, scapholunate dislocation, and
      scaphoid fractures. The other injuries are trivial. Symptoms include pain and
      loss of wrist strength, reversible for an acute and well-treated lesion. Too
      often, these ligament injuries are diagnosed late. For delays longer than 6
      weeks, ligament repair is ineffective. These old, complex lesions are potentially
      highly arthritic in the radiocarpal and mediocarpal joints. Improvements in wrist
      surgery have mitigated these chronic lesions. Various surgical techniques can
      preserve a functional wrist; wrist arthrodesis is no longer the only solution for
      these arthritic wrists. Over the past decade, arthroscopy has contributed to
      better understanding the injuries of the carpus as well as to better healing
      them. For acute or chronic ligament injuries without degenerative osteoarthritis,
      arthroscopy is the treatment of the future. This technique involves a long
      learning curve and the various arthroscopic techniques must be validated. 

PMID- 24461234
TI  - Outcome evaluation in pediatric orthopedics.
AB  - Outcome evaluation is an objective procedure to determine the impact and success
      of a therapeutic program, focusing on the patient's well being in daily life. It
      is important not to confuse the different concepts found in the health status
      classification and quality of life evaluation. Both are suitable for outcome
      evaluation and may be used according to the principles of evidence-based
      medicine. Outcome evaluation of a therapeutic program may be compared to a search
      in the literature and the level of evidence. The goal is to achieve direct
      benefits for the patient and society. Strategies to improve daily practice may be
      developed. Scientific societies can create database for outcome evaluation and
      develop standardized protocols for longitudinal outcome follow-up, as well as
      proposing this type of study to health authorities. Based on these results, a
      global view of the patient can be taken into consideration to influence medical,
      socioeconomic and health management patient care. 

PMID- 24461235
TI  - Primary shoulder reverse arthroplasty: surgical technique.
AB  - Total reverse shoulder replacement is now a very common surgical procedure that
      has been shown to be effective in the treatment of rotator cuff tear
      arthropathies or massive rotator cuff tears with pseudo paralysis, even without
      arthritis. However, the survival curves of the oldest series decrease between 8
      and 10 years after arthroplasty (events: implant survival, or worsening of
      clinical outcome) which explains why the indication for this type of arthroplasty
      is usually limited to patients over seventy. Moreover, details and technical
      modifications have been suggested to improve the surgical technique, the quality
      of fixation and the mechanical conditions of this non-anatomical prosthesis to
      improve clinical outcome and implant survival. Within the framework of primary
      surgery, excluding traumatic or revision surgery, the primary indications for
      this option are massive rotator cuff tears with (or without) osteoarthritis and
      primary osteoarthritis with rotator cuff tears and/or with severe glenoid wear
      and finally, rheumatoid arthritis. The purpose of this conference was to assess
      and describe the most important preoperative criteria and surgical conditions
      necessary for this procedure as well as specific technical details about the
      surgical procedure itself based on available options and options under evaluation
      such as the positioning of the glenoid component (lateralization, bone graft,
      orientation) and the association of muscle transfers. 

PMID- 24461236
TI  - Meaningful activities in the nursing home.

PMID- 24461237
TI  - Survey deficiencies are not reliable for drawing conclusions about aspects of
      quality.

PMID- 24461238
TI  - Baseball reminiscence league: a model for supporting persons with dementia.
AB  - Reminiscence therapy for persons with dementia improves socialization and quality
      of life. Herein we report the development of reminiscence groups based around
      memories of professional baseball. Preliminary feedback suggests that this can be
      a successful approach to enhancing quality of life for persons with mild to
      moderate dementia. 

PMID- 24461240
TI  - Clinical uncertainties in the approach to long term care residents with possible
      urinary tract infection.
AB  - Urinary tract infection (UTI) is arguably the most common infection in the long
      term care (LTC) setting. Making the diagnosis of UTI and deciding when to
      initiate treatment with antimicrobial therapy is a challenge to all LTC
      providers. Widespread prevalence of asymptomatic bacteriuria, lack of an accepted
      clinical or laboratory gold standard to start antibiotics for UTI, and a high
      prevalence of cognitive impairment in the LTC population all contribute to this
      challenge. Several consensus based criteria for diagnosing UTI have been
      published, though these vary from each other owing to different intended
      purposes. The McGeer and updated Stone criteria are intended for surveillance and
      benchmarking purposes. The 2005 Loeb criteria represent minimal criteria for the
      initiation of antimicrobial therapy. Our review focuses on residents without a
      urinary catheter. The Loeb criteria should be updated, by inclusion of isolated
      fever in those with profound cognitive impairment as well as scrotal or prostate
      swelling tenderness to be consistent with the updated McGeer criteria by Stone et
      al. Urine testing and antimicrobial therapy should not be ordered in those with
      isolated nonspecific signs or noninfectious symptoms such as fatigue or delirium.
      Both cavalier urine testing and unnecessary antimicrobial therapy contribute to
      direct patient harm as well as the rapidly escalating threat of antimicrobial
      resistance. Observation and monitoring of residents in whom the diagnosis of UTI
      is unclear is a best practice that should be implemented. Facilities should
      consider addressing UTI management as part of their quality assurance and
      performance improvement process. 

PMID- 24461241
TI  - Cognitive and physical stimulation therapy.

PMID- 24461239
TI  - Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia.
AB  - Sarcopenia, a newly recognized geriatric syndrome, is characterized by age
      related decline of skeletal muscle plus low muscle strength and/or physical
      performance. Previous studies have confirmed the association of sarcopenia and
      adverse health outcomes, such as falls, disability, hospital admission, long term
      care placement, poorer quality of life, and mortality, which denotes the
      importance of sarcopenia in the health care for older people. Despite the
      clinical significance of sarcopenia, the operational definition of sarcopenia and
      standardized intervention programs are still lacking. It is generally agreed by
      the different working groups for sarcopenia in the world that sarcopenia should
      be defined through a combined approach of muscle mass and muscle quality,
      however, selecting appropriate diagnostic cutoff values for all the measurements
      in Asian populations is challenging. Asia is a rapidly aging region with a huge
      population, so the impact of sarcopenia to this region is estimated to be huge as
      well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia
      research in Asia, and we collected the best available evidences of sarcopenia
      researches from Asian countries to establish the consensus for sarcopenia
      diagnosis. AWGS has agreed with the previous reports that sarcopenia should be
      described as low muscle mass plus low muscle strength and/or low physical
      performance, and we also recommend outcome indicators for further researches, as
      well as the conditions that sarcopenia should be assessed. In addition to
      sarcopenia screening for community-dwelling older people, AWGS recommends
      sarcopenia assessment in certain clinical conditions and healthcare settings to
      facilitate implementing sarcopenia in clinical practice. Moreover, we also
      recommend cutoff values for muscle mass measurements (7.0 kg/m(2) for men and 5.4
      kg/m(2) for women by using dual X-ray absorptiometry, and 7.0 kg/m(2) for men and
      5.7 kg/m(2) for women by using bioimpedance analysis), handgrip strength (<26 kg
      for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number
      of challenges remained to be solved in the future. Asia is made up of a great
      number of ethnicities. The majority of currently available studies have been
      published from eastern Asia, therefore, more studies of sarcopenia in south,
      southeastern, and western Asia should be promoted. On the other hand, most Asian
      studies have been conducted in a cross-sectional design and few longitudinal
      studies have not necessarily collected the commonly used outcome indicators as
      other reports from Western countries. Nevertheless, the AWGS consensus report is
      believed to promote more Asian sarcopenia research, and most important of all, to
      focus on sarcopenia intervention studies and the implementation of sarcopenia in
      clinical practice to improve health care outcomes of older people in the
      communities and the healthcare settings in Asia.

PMID- 24461242
TI  - Response to the letter to the editor: "Frailty consensus: a call to action".

PMID- 24461243
TI  - Response to the letter to the editor: "What is missing in the validation of
      frailty instruments?".

PMID- 24461244
TI  - Response to the letter from Xue And Varadhan: "What is missing in the validation
      of frailty instruments?".

PMID- 24461245
TI  - Response to the letter to the editor: "Frailty consensus: a call to action".

PMID- 24461246
TI  - Response to the letter to the editor entitled "What is missing in the validation
      of frailty instruments?" by Drs Xue and Varadhan: The Toulouse frailty clinic, 1
      year of clinical experience.

PMID- 24461247
TI  - Response to the letter to the editor from Xue and Varadhan titled "What is
      missing in the validation of frailty instruments?".

PMID- 24461248
TI  - Two-stage revision for prosthetic joint infection: outcome and role of
      reimplantation microbiology in 107 cases.
AB  - Two-stage revision is widely used for the treatment of prosthetic joint
      infections. However, the duration of antibiotic treatment between stages and role
      of reimplantation microbiology are controversial. The purpose of this study was
      to evaluate the outcome and influence of the reimplantation microbiology of two
      staged revisions with 6 weeks of antibiotic treatment. We retrospectively
      reviewed 107 patients treated with two-stage revision between 2001 and 2009. The
      overall treatment success rate was 94.4%. The reimplantation cultures were
      positive in 5/97 (5.2%) cases, and only one of them failed. Therefore, we
      achieved excellent results with a 6-week course of antibiotics between stages in
      two-stage revision. Positive reimplantation cultures do not seem to be associated
      with worse outcomes.

PMID- 24461249
TI  - [Psychosocial aspects in a cohort of vertically transmitted human
      immunodeficiency virus-infected adolescents].
AB  - INTRODUCTION: Thanks to advances in antiretroviral treatment, children with HIV
      infections through vertical transmission have improved their life expectancy.
      However, new challenges have emerged. We propose this study in order to determine
      the psychosocial aspects and knowledge of infections in a cohort of adolescents
      with vertically transmitted HIV infections. METHODS: Patients with vertically
      acquired HIV infection between 12 and 19 years old were included. Data were
      obtained through semi-structured interviews and a Strengths and Difficulties
      Questionnaire for emotional and behavioral disorders screening. RESULTS: We
      evaluated 96 patients (58% females) with a median age of 15 years (11-19.1) and a
      median age at diagnosis of 1.70 years (0-12.2). The median CD4 count was
      626cells/mm(3) (132-998), and the viral load was<50cp/ml in 72% of patients.
      Among them, 90% attended school and 60% repeated at least one course. Although
      81% of them knew of their diagnosis, only 30% understood their disease, with
      18.2% having discussed it with friends. Six unwanted pregnancies occurred during
      the study period. Strengths and Difficulties Questionnaire showed hyperactivity
      risk in 33%. CONCLUSION: A high percentage of adolescents show difficulties in
      several areas (disease knowledge, peer relationship, school failure...) that can
      have an impact on their adult lives. Further studies are needed to evaluate their
      origin and development in depth, as well as interventions to modify this
      situation.

PMID- 24461250
TI  - Resin bonding to three types of polyaryletherketones (PAEKs)-durability and
      influence of surface conditioning.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate the bond strength
      and durability of adhesive bonding systems to amorphous and crystalline PEKK and
      fiber-reinforced PEEK using five types of surface conditioning methods. METHODS:
      One hundred and fifty specimens of each material were conditioned mechanically
      and chemically, bonded with Multilink Automix to Plexiglas tubes, filled with
      Multicore Flow, and stored in water at 37 degrees C for 3, 30 and 150 days. The
      long-term storage series were thermal cycled between 5 and 55 degrees C for
      10,000 times (30 days) or for 37,500 times (150 days) prior to tensile bond
      strength test (TBS). Statistical analysis was performed using Kruskal-Wallis and
      Wilcoxon tests with a Bonferroni-Holm correction for multiple testing
      (alpha=0.05). RESULTS: Fiber-reinforced PEEK exhibited higher bond strengths in
      all five conditioning groups and at all three storage times than crystalline and
      amorphous PEKK, which showed lowest TBS. Highest TBS was achieved after
      conditioning with silica coating and priming (Rocatec Soft, Monobond Plus,
      Luxatemp Glaze & Bond; TBS up to 23.6MPa). SIGNIFICANCE: The conditioning method
      has a significant influence to the bond strength of the bonding to the amorphous
      and crystalline PEKKs and fiber-reinforced PEEKs.

PMID- 24461251
TI  - Why decision making may not require awareness.
AB  - Newell & Shanks (N&S) argue against the idea that any significant role for
      unconscious influences on decision making has been established by research to
      date. Inasmuch as this conclusion applies to the idea of an "intelligent
      cognitive unconscious," we would agree. Our concern is that the article could
      lead the unwary to conclude that there are no unconscious influences on decision
      making - and never could be. We give reasons why this may not be the case. 

PMID- 24461252
TI  - Failure of Helicobacter pylori eradication and age are independent risk factors
      for recurrent neoplasia after endoscopic resection of early gastric cancer in 283
      patients.
AB  - BACKGROUND: Whether the incidence of metachronous gastric dysplasia and cancer
      could be decreased by eradication of Helicobacter pylori after endoscopic
      submucosal dissection (ESD) for early gastric cancer (EGC). AIM: To compare the
      incidence of metachronous gastric lesion in the eradicated group and the
      persistent group. Second end point is to evaluate the risk factors for
      metachronous gastric lesions after ESD for EGC. METHODS: In a single centre,
      between May 2007 and May 2010, the patients who had evidence of H. pylori
      infection at the time of ESD for EGC were included, and the follow-up data were
      analysed retrospectively. RESULTS: We enrolled 283 patients who have shown H.
      pylori infection at the time of ESD for EGC. Successful eradication was achieved
      for 214 patients (75.6%) (Eradicated group), and 69 patients (24.4%) showed
      persistent H. pylori infection (Persistent group). Metachronous gastric lesions
      developed in 13 (18.8%) in the persistent group and 18 (8.4%) in the eradicated
      group (P = 0.016). In the >=60-year-old group, the cumulative incidence of
      metachronous gastric cancer showed a significant increase (P = 0.012). Cumulative
      hazard ratio of subsequent gastric metachronous lesions differed between the
      eradication group and the persistent infection group (OR = 2.322, 95% CI = 1.136
      4.744, P = 0.021), and >=60 age at the time of endoscopic resection (OR = 2.803,
      95% CI = 1.207-6.509, P = 0.016). CONCLUSIONS: Both persistent H. pylori
      infection and old age (>=60) are independent risk factors for the increased
      incidence of metachronous gastric cancer.

PMID- 24461253
TI  - Evaluation of a standardized sedation assessment for opioid administration in the
      post anesthesia care unit.
AB  - The impact of opioid-related sedation progressing to respiratory depression in
      the Post Anesthesia Care Unit (PACU) can be extensive; however, there is a
      paucity of research on the subject of standardized assessment tools to prevent
      adverse events. The purposes of this study were: (1) to measure the efficacy of a
      standardized method of assessing sedation and administering opioids for pain
      management via the Pasero Opioid-Induced Sedation Scale (POSS) with interventions
      in the PACU; (2) to increase PACU nurses' confidence in assessing sedation
      associated with opioid administration for pain management and in the quality of
      care provided in their clinical area; and (3) to facilitate PACU and
      postoperative clinical unit nurses' communications during patient handoffs
      regarding safe opioid administration. A quasi-experimental design was used to
      evaluate the POSS protocol. Two PACUs and six nursing units receiving
      postsurgical patients in a Midwestern inner-city hospital served as the setting
      for this research. Medical records were surveyed for outcome data to evaluate the
      efficacy of the care protocol in two patient cohorts before and after
      implementation of the POSS protocol. Nurses completed a written survey to
      identify changes in satisfaction with nurse-to-nurse communication, perceptions
      of quality of care, and confidence with opioid administration. The final sample
      included 842 PACU patients and 67 nurses from the PACU and clinical units. The
      intervention did not significantly change PACU length of stay or amount of
      administered opioids and patients were noted to be more alert at time of
      discharge from the PACU. Nurses reported increased perceptions of quality of care
      and confidence in opioid administration. The findings from this study support the
      use of the POSS Scale with interventions in the PACU care protocols. 

PMID- 24461254
TI  - Thermodynamic parameters for adsorption equilibrium of heavy metals and dyes from
      wastewaters.
AB  - This meta-analysis evaluates adsorption studies that report thermodynamic
      parameters for heavy metals and dyes from wastewaters. The adsorbents were
      derived from agricultural waste, industrial wastes, inorganic particulates, or
      some natural products. The adsorption mechanisms, derivation of thermodynamic
      relationships, and possible flaws made in such evaluation are discussed. This
      analysis shows that conclusions from the examined standard enthalpy and entropy
      changes are highly contestable. The reason for this flaw may be the poor physical
      structure of adsorbents tested, such that pore transport controlled the solute
      flux, leaving a surface reaction process near equilibrium. 

PMID- 24461255
TI  - Competitive adsorption of metals on cabbage waste from multi-metal solutions.
AB  - This study assessed the adsorption capacity of the agro-waste 'cabbage' as a
      biosorbent in single, binary, ternary and quaternary sorption systems with
      Cu(II), Pb(II), Zn(II) and Cd(II) ions. Dried and ground powder of cabbage waste
      (CW) was used for the sorption of metals ions. Carboxylic, hydroxyl, and amine
      groups in cabbage waste were found to be the key functional groups for metal
      sorption. The adsorption isotherms obtained could be well fitted to both the mono
      and multi-metal models. In the competitive adsorption systems, cabbage waste
      adsorbed larger amount of Pb(II) than the other three metals. However, the
      presence of the competing ions suppressed the sorption of the target metal ions.
      Except the case of binary system of Cd(II)-Zn(II) and Cd(II)-Cu(II), there was a
      linear inverse dependency between the sorption capacities and number of different
      types of competitive metal ions. 

PMID- 24461256
TI  - Partial depolymerization of enzymolysis lignin via mild hydrogenolysis over Raney
      Nickel.
AB  - In this work, partial depolymerization of enzymolysis lignin collected from a
      woody biomass-to-ethanol process was studied via mild hydrogenolysis under the
      catalysis of Raney Ni. The depolymerized lignin products were low molecular
      weight oligomers with increased hydroxyl values. The solvent selected, use of
      base and various reaction parameters were all found to influence yield of
      depolymerization, the molecular weight and hydroxyl value of the hydrogenated
      product. The depolymerized lignins displayed greatly enhanced solubility in
      organic solvents, and therefore would have great potential to be used as
      feedstock for many valuable thermosetting polymer applications. 

PMID- 24461257
TI  - Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23
      duplication.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the
      presynaptic neuromuscular junction, typically occurring in adults as a
      paraneoplastic syndrome. Only rare cases have been reported in childhood. In most
      childhood cases, malignancies have not been detected but a propensity to
      autoimmune disease was noticed. Nevertheless, little is known about genetic
      factors that may contribute to the susceptibility of an individual to develop
      LEMS. We report on a 13-year-old girl, known with the Xp11.22-p11.23 duplication
      syndrome, who presented with severe non-paraneoplastic LEMS. The potential role
      of this microduplication syndrome in the development of LEMS is explored.
      Previous literature review of twelve Xp11.2 duplication syndrome patients showed
      that three of them suffered from various autoimmune diseases. The common
      duplicated region in those three patients and the presented case comprises 12
      disease-associated genes including the FOXP3 (Forkhead Box P3) and WAS (Wiskott
      Aldrich syndrome) gene, both implicated in immune function. However, it is
      unclear whether increased gene dosage of one or both of these genes can cause
      susceptibility to autoimmune diseases. In conclusion, the presented case
      emphasizes that autoimmune disease is a recurrent feature of the Xp11.2
      duplication syndrome, which should be considered in the follow-up of these
      patients. The exact mechanism underlying this autoimmune propensity remains to be
      elucidated. 

PMID- 24461258
TI  - Evaluation of functional goal outcomes using the Canadian Occupational
      Performance Measure (COPM) following Deep Brain Stimulation (DBS) in childhood
      dystonia.
AB  - PURPOSE: To evaluate the functional goal-directed outcomes of Deep Brain
      Stimulation (DBS) in childhood dystonia according to aetiology and to explore
      relationship with a traditional impairment-based measure. METHOD: This is a
      prospective case series study involving thirty children with dystonia with a 1
      year follow-up post-DBS. The Canadian Occupational Performance Measure (COPM) and
      Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were used as primary outcome
      measures. Results were analysed based on aetiology in 3 groups: 1.
      primary/primary plus dystonia; 2. secondary dystonia-cerebral palsy (CP); 3.
      secondary dystonia-non-CP group. Correlation between functional outcome using
      COPM and dystonia improvement as captured by BFMDRS was measured. RESULTS: All
      groups demonstrated significant improvement in individualised goal attainment,
      measured with the COPM, at 1-year post-DBS. The secondary dystonia-CP group also
      achieved significant improvement at 6 months for performance and satisfaction
      scores. In the majority of secondary dystonias, the BFMDRS failed to demonstrate
      significant improvement. A linear correlation between change in BFMDRS and COPM
      scores was observed when the entire cohort was analysed.
      INTERPRETATION/CONCLUSIONS: DBS improved functional performance, independently of
      the dystonic phenotype. Improvements in individualized COPM functional goal areas
      were seen in the absence of significant changes in BFMDRS scores, highlighting
      the relative insensitivity of impairment scales in this patient group.

PMID- 24461259
TI  - Real-time advanced spinal surgery via visible patient model and augmented reality
      system.
AB  - This paper presents an advanced augmented reality system for spinal surgery
      assistance, and develops entry-point guidance prior to vertebroplasty spinal
      surgery. Based on image-based marker detection and tracking, the proposed camera
      projector system superimposes pre-operative 3-D images onto patients. The
      patients' preoperative 3-D image model is registered by projecting it onto the
      patient such that the synthetic 3-D model merges with the real patient image,
      enabling the surgeon to see through the patients' anatomy. The proposed method is
      much simpler than heavy and computationally challenging navigation systems, and
      also reduces radiation exposure. The system is experimentally tested on a
      preoperative 3D model, dummy patient model and animal cadaver model. The
      feasibility and accuracy of the proposed system is verified on three patients
      undergoing spinal surgery in the operating theater. The results of these clinical
      trials are extremely promising, with surgeons reporting favorably on the reduced
      time of finding a suitable entry point and reduced radiation dose to patients. 

PMID- 24461260
TI  - 2,3,7,8-Tetrachlorodibezo-p-dioxin exposure and prostate cancer: a meta-analysis
      of cohort studies.
AB  - OBJECTIVE: To perform a meta-analysis of cohort studies and evaluate the
      association between exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      prostate cancer quantitatively. STUDY DESIGN: Publications before April 2012
      about populations exposed to TCDD were searched in PubMed. Only cohort studies
      were included. Extraction and quality assessment of included articles was
      performed independently by two authors using the MOOSE guidelines. METHODS: A
      total of 17 cohort studies on prostate cancer with information about standardized
      mortality ratios (SMR), risk ratio (RR), standardized incidence ratios (SIR) and
      TCDD exposure were included. SMRs and RRs were pooled separately after weighing
      each study by calculating the inverse of the estimated variance. RESULTS: Based
      on the 13 reported SMRs or SIRs, the meta-analysis yielded a meta-SMR of 1.26
      (95% confidence interval 1.00-1.57, P = 0.046). The meta-RR, based on four
      reported RR from four cohorts, was 1.04 (95% confidence interval 0.85-1.28).
      Begg's funnel plot showed little evidence of publication bias (Egger's test P
      value = 0.817). CONCLUSION: This meta-analysis suggests that exposure to TCDD is
      associated with increased risk of prostate cancer.

PMID- 24461262
TI  - Degraded conditions: confounds in the study of decision making.
AB  - I raise a consideration complementary to those raised in the target article. Many
      of the most widely cited studies on decision making involve introspection in
      degraded conditions, namely, conditions in which agents have no reason for the
      decisions they reach. But the fact that confabulation occurs in degraded
      conditions does not impugn the reliability of introspection in non-degraded
      conditions, that is, in cases in which a subject actually does make a choice for
      a reason. 

PMID- 24461261
TI  - Changes in socio-economic differences in adolescent self-reported health between
      15 and 19 years of age: a longitudinal study.

PMID- 24461264
TI  - [Post-lasik corneal ectasia in patients with significant differences in
      keratometry readings between both eyes].
AB  - OBJECTIVES: A study is made on the incidence of corneal ectasia after laser in
      situ keratomileusis (LASIK) in patients with large differences in mean
      keratometry (MK) readings between both eyes (OU). Visual outcomes were also
      evaluated. METHODS: The medical records of 164,603 patients (315,259 eyes) who
      underwent LASIK from January 2003 to December 2011 were reviewed in order to
      identify patients with a difference in MK of >= 1.25 D between OU. The main
      outcome measures were incidence of ectasia after LASIK, and visual outcome.
      RESULTS: A total of 35 eyes that met the inclusion criteria were found.
      Functional and visual results were those expected for myopia studies. After a
      minimum follow-up of 2 years, no corneal ectasia was found in 3 eyes (2
      patients). CONCLUSIONS: The possibility of finding a patient with an asymmetry in
      MK and normal topography is low (0.021%), and it does not seem to be a
      contraindication of LASIK. Although no corneal ectasia was found in this case
      series, and as it is a potentially sight-threatening complication, patients with
      very different MK between OU should be studied carefully before undergoing LASIK.

PMID- 24461265
TI  - [Does time fly when you're having fun?].

PMID- 24461266
TI  - Lithium carbonate induced idiopathic intracranial hypertension.

PMID- 24461267
TI  - Damage control resuscitation: history, theory and technique.
AB  - Damage control resuscitation (DCR) represents the natural evolution of the
      initial concept of damage control surgery. It currently includes early blood
      product transfusion, immediate arrest and/or temporization of ongoing hemorrhage
      (i.e., temporary intravascular shunts and/or balloon tamponade) as well as
      restoration of blood volume and physiologic/hematologic stability. As a result,
      DCR addresses the early coagulopathy of trauma, avoids massive crystalloid
      resuscitation and leaves the peritoneal cavity open when a patient approaches
      physiologic exhaustion without improvement. This concept also applies to severe
      injuries within anatomical transition zones as well as extremities. This review
      will discuss each of these concepts in detail. 

PMID- 24461268
TI  - The merits of cell salvage in arthroplasty surgery: an overview.
AB  - Arthroplasty entails considerable exposure to allogenic blood transfusion. Cell
      salvage with washing is a contemporary strategy that is not universally used
      despite considerable potential benefits. We searched Embase and Medline to
      determine if blood salvage with washing during primary and/or revision hip and
      knee arthroplasty results in lower rates of transfusion and postoperative
      complications. We included 10 studies in our analysis, which we rated according
      to Downs and Black criteria. With primary knee arthroplasty, there was a
      reduction in transfusion rate from 22% to 76% and a 48% reduction in transfusion
      volume (n = 887). With primary hip arthroplasty, there was a reduction from 69%
      to 73% in transfusion rate and a 31% reduction in transfusion volume (n = 239).
      There was a significant decrease in length of hospital stay (9.6 v. 13.6 d).
      Studies of revision arthroplasty reported a 31%-59% reduction in transfusion
      volume (n = 241). The available evidence demonstrates reduced exposure to
      allogenic blood with the use of salvage systems. Studies have been underpowered
      to detect differences in infection rates and other postoperative complications.
      Future cost analysis is warranted. 

PMID- 24461269
TI  - CAGS and ACS evidence based reviews in surgery. 48. What is the effect of
      screening mammography on breast cancer incidence?

PMID- 24461270
TI  - Sustainability, cost and exchange.

PMID- 24461271
TI  - Impaired Theory of Mind and psychosocial functioning among pediatric patients
      with Type I versus Type II bipolar disorder.
AB  - Deficits in Theory of Mind (ToM) have been documented among pediatric patients
      with Bipolar Disorder (BD). However, fewer studies have directly examined
      differences between type I and type II patients and whether or not ToM deficits
      are related to psychosocial difficulties. Therefore, the aim of this study was to
      compare type I versus type II pediatric bipolar patients and matched Healthy
      Controls (HC) on ToM and interpersonal functioning tasks. All participants
      completed the Revised Mind in the Eyes Task (MET), the Cognitive and Emotional
      Perspective Taking Task (CEPTT), and the Index of Peer Relations (IPR). Type I BD
      patients reported greater peer difficulties on the IPR compared to HC, and also
      performed more poorly on the MET and the cognitive condition of the CEPTT, but
      did not differ significantly on the emotional condition. There were no
      significant group differences between type II BD patients and HC. More impaired
      ToM performance was associated with poorer interpersonal functioning. Type I BD
      patients show deficits in the ability to understand another's mental state,
      irrespective of emotional valence. Deficits in understanding others' mental
      states could be an important treatment target for type I pediatric patients with
      BD. 

PMID- 24461272
TI  - Evaluating the obtunded patient after cardiac surgery: the role of continuous
      electroencephalography.
AB  - PURPOSE: This prospective study was designed to evaluate the role of continuous
      electroencephalography (EEG) in the management of adult patients with
      neurological dysfunction early after cardiac surgery. MATERIALS AND METHODS:
      Seven hundred twenty-three patients undergoing cardiac surgery between December
      2010 and June 2011 were divided into 2 groups based on the presence or absence of
      post-operative neurological dysfunction. All patients with neurological
      dysfunction underwent continuous EEG. RESULTS: Neurological dysfunction was
      diagnosed in 12 patients (1.7%), of whom 5 (42%) did not regain consciousness
      after surgery, 4 (33%) had a clinical event suspicious for seizure and 3 (25%)
      had neurological deficits. Continuous EEG showed that 2 of the 5 patients who
      failed to regain consciousness, without clinical signs of seizures, were in
      electrographic non-convulsive focal status epilepticus. Periodic discharges were
      present in the continuous EEGs of 3 patients. Three additional patients (25%) had
      abnormal movements that continuous EEG demonstrated was not due to seizure
      activity. CONCLUSIONS: Non-convulsive status epilepticus may be an under
      recognized cause of obtundation early after cardiac surgery. Continuous EEG
      monitoring is a non-invasive test that can identify patients that may benefit
      from anti-epileptic medication. Larger comparative studies are required to
      establish whether this leads to significant improvements in patient outcomes.

PMID- 24461273
TI  - Indocyanine green fluorescence imaging in the surgical management of liver
      cancers: current facts and future implications.
AB  - Imaging detection of liver cancers and identification of the bile ducts during
      surgery, based on the fluorescence properties of indocyanine green, has recently
      been developed in liver surgery. The principle of this imaging technique relies
      on the intravenous administration of indocyanine green before surgery and the
      illumination of the surface of the liver by an infrared camera that
      simultaneously induces and collects the fluorescence. Detection by fluorescence
      is based on the contrast between the (fluorescent) tumoral or peri-tumoral
      tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine
      green fluorescence imaging is capable of identification of new liver cancers and
      enables the characterization of known hepatic lesions in real time during liver
      resection. The purpose of this paper is to present the fundamental principles of
      fluorescence imaging detection, to describe successively the practical and
      technical aspects of its use and the appearance of hepatic lesions in
      fluorescence, and to expose the diagnostic and therapeutic perspectives of this
      innovative imaging technique in liver surgery. 

PMID- 24461274
TI  - Peering into the looking glass: hot topics for 2014.

PMID- 24461275
TI  - Letter to the editor.

PMID- 24461276
TI  - Response to letter to the editor.

PMID- 24461277
TI  - A prospective randomized study of the effectiveness of aromatherapy for relief of
      postoperative nausea and vomiting.
AB  - INTRODUCTION: Postoperative nausea and vomiting (PONV) is a major concern for
      patients having surgery under general anesthesia as it causes subjective distress
      along with increased complications and delays in discharge from the hospital.
      Aromatherapy represents a complementary and alternative therapy for the
      management of PONV. PURPOSE: The objective of this study was to compare the
      effectiveness of aromatherapy (QueaseEase, Soothing Scents, Inc, Enterprise, AL)
      versus an unscented inhalant in relieving PONV. METHODS: One hundred twenty-one
      patients with postoperative nausea were randomized into a treatment group
      receiving an aromatic inhaler and a control group receiving a placebo inhaler to
      evaluate the effectiveness of aromatherapy. FINDINGS: Initial and follow-up
      nausea assessment scores in both treatment and placebo groups decreased
      significantly (P < .01), and there was a significant difference between the two
      groups (P = .03). Perceived effectiveness of aromatherapy was significantly
      higher in the treatment group (P < .001). CONCLUSIONS: Aromatherapy was favorably
      received by most patients and represents an effective treatment option for
      postoperative nausea.

PMID- 24461278
TI  - Controlled breathing with or without peppermint aromatherapy for postoperative
      nausea and/or vomiting symptom relief: a randomized controlled trial.
AB  - PURPOSE: With little scientific evidence to support use of aromatherapy for
      postoperative nausea and/or vomiting (PONV) symptoms, this study evaluated
      controlled breathing with peppermint aromatherapy (AR) and controlled breathing
      alone (CB) for PONV relief. DESIGN: A single blind randomized control trial
      design was used. METHODS: On initial PONV complaint, symptomatic subjects
      received either CB (n = 16) or AR (n = 26) intervention based on randomization at
      enrollment. A second treatment was repeated at 5 minutes if indicated. Final
      assessment occurred 10 minutes post initial treatment. Rescue medication was
      offered for persistent symptoms. FINDINGS: Among eligible subjects, PONV
      incidence was 21.4% (42/196). Gender was the only risk factor contributing to
      PONV symptoms (P = .0024). Though not statistically significant, CB was more
      efficacious than AR, 62.5% versus 57.7%, respectively. CONCLUSIONS: CB can be
      initiated without delay as an alternative to prescribed antiemetics. Data also
      support use of peppermint AR in conjunction with CB for PONV relief.

PMID- 24461279
TI  - Effect of preoperative incentive spirometry patient education on patient outcomes
      in the knee and hip joint replacement population.
AB  - PURPOSE: This study examined the effects of preoperative incentive spirometry
      (IS) education (POISE) on postoperative outcomes for knee and hip total joint
      replacement patients. DESIGN: In this prospective study, 140 patients were
      randomized to Group 1 (POISE intervention = 50 completing) or Group 2 (no
      intervention = 56 completing) (34 dropped). METHODS: The Group 1 intervention
      consisted of formal instruction preoperatively for IS home use, postoperative
      use, and IS volumes documentation. Group 2 patients received no intervention.
      Patients recorded postoperative IS volumes, which were used to determine return
      to baseline volume. FINDINGS: One hundred six patients completed the study. Most
      were Caucasian females averaging 64 years. Although IS return to baseline volume
      time was not significantly different between groups, POISE patients had fewer
      postoperative complications, hospital days, and charges. POISE patients ranked
      the intervention as helpful. CONCLUSIONS: Although IS volumes were not
      significantly different between groups, POISE patients had better outcomes and
      ranked the intervention as helpful.

PMID- 24461280
TI  - Content validity testing of questions for a patient satisfaction with general
      anesthesia care instrument.
AB  - INTRODUCTION: Patient satisfaction with any health care experience is the result
      of a complex set of interactions between the patient and the health system in
      which care is received. Measuring patient satisfaction allows quantification of
      the congruence between the expectations of care and the care that is received. It
      is important to quantify satisfaction with care because it involves the patient
      in the care experience and decreases the potential gap between expected and
      actual care delivered over time. Despite the benefits of measuring satisfaction
      with anesthesia care, this outcome has been historically understudied possibly
      because of a lack of reliable tools that measure the construct. PURPOSE: The
      purpose of this study was to test the content validity of items derived from an
      integrated review of studies that measured patient satisfaction with anesthesia
      care. METHODS: The content validity of the questions was tested using an expert
      panel. A total of 13 nurse anesthetists consented to participate in the study as
      expert panel members. Each expert panel member evaluated the items for content
      validity on a 4-point scale. Both an Individual Content Validity Index (I-CVI)
      and a Scale Content Validity Index (S-CVI) were calculated. RESULTS: All I-CVI
      scores were greater than 0.8. The range of I-CVI was 0.833 to 1.0. The average
      scale Content Validity Index (S-CVI/ave) was 0.979. CONCLUSION: High content
      validity of all items was supported by an expert panel of anesthesia providers.
      The high level of agreement among raters related to the content of the general
      anesthesia statements supports progressing to the next step in instrument
      development.

PMID- 24461281
TI  - Perianesthesia nursing-beyond the critical care skills.
AB  - Provision of patient care within the perianesthesia specialty is demanding in
      nature. Although a nurse may be well equipped with the assessment, planning, and
      critical thinking skills required for these fast-paced areas, there are other
      competencies to be developed. These include skills in mentorship, communication,
      crisis management, and competency as an ambassador of patient safety. Barriers to
      developing these skills may include a high patient acuity and turnover, a sense
      of isolation from other departments, and strong hierarchical structures. However,
      there are resources and strategies that nurses can leverage to facilitate
      development of these less-technical, "softer" skills. In this article, the author
      reviews some of the unique demands commonly seen within the perianesthesia
      specialty. Methods to address these challenges are shared to facilitate an
      enjoyable career in this dynamic environment.

PMID- 24461282
TI  - Ensuring safe discharge for patients with pacemakers and implantable cardiac
      defibrillators (ICDs).

PMID- 24461283
TI  - Chest tube removal: an expanded role for the bedside nurse.

PMID- 24461284
TI  - Understanding patient safety through a systems approach.

PMID- 24461286
TI  - Life's lessons of scouting, leadership, and mentorship.

PMID- 24461287
TI  - The origins, development, effects, and future of the WHO Framework Convention on
      Tobacco Control: a personal perspective.
AB  - Worldwide, more than 1 billion people use tobacco, resulting in about 6 million
      deaths per year. The tobacco industry's documented history of subverting control
      efforts required innovative approaches by WHO--led by Gro Harlem Brundtland-
      including invocation of its constitutional authority to develop treaties. In
      2003, WHO member states adopted the WHO Framework Convention on Tobacco Control
      (WHO FCTC). In the decade since, 177 countries have ratified and started to
      implement its full provisions. Success has been tempered by new challenges.
      Tobacco use has fallen in countries that are members of the Organisation for
      Economic Co-operation and Development but increased in low-income and middle
      income countries, a result in no small part of illicit trade and cheap products
      from China and other unregulated state monopolies. This review of 50 years of
      policy development aimed at reducing the burden of disease attributable to
      tobacco reviews the origins and strategies used in forging the WHO FCTC, from the
      perspective of one who was there.

PMID- 24461288
TI  - Synthesis of neoglycosphingolipid from methoxyamino-functionalized ceramide.
AB  - An efficient approach for the synthesis of a methoxyamino-functionalized ceramide
      was established from phytosphingosine using specific Nbeta->Nalpha acyl migration
      of the octadecanoyl group during the removal of Nalpha-Fmoc protective group. One
      step glycoblotting reaction of the ceramide mimic with lactose afforded a
      neoglycosphingolipid showing potent inhibitory activity against recombinant
      endoglycoceramidase II from Rhodococcus sp. 

PMID- 24461289
TI  - Benzimidazole CB2 agonists: design, synthesis and SAR.
AB  - A new series of CB2-selective agonists containing a benzimidazole core is
      reported. Design, synthesis, SAR and pharmacokinetic data for selected compounds
      are described. 

PMID- 24461290
TI  - Synthesis and haemolytic activity of novel salts made of nicotine alkaloids and
      bile acids.
AB  - A series of novel salts made of nicotine alkaloids and bile acids were
      synthesized and their haemolytic activity was examined in vitro using human
      erythrocytes. All compounds were characterized by spectroscopic methods. The
      novel salts show membrane-perturbing properties inducing the erythrocyte shape
      alterations and haemolysis in dose-dependent manner. Nicotine decreases the
      membrane interacting potential of bile acids in the novel compounds. The presence
      of sulfur or selenium atom in the nicotine molecule affects the haemolytic
      activity of its novel salts depending on the hydrophobicity of bile acids. 

PMID- 24461292
TI  - Heterocyclic core analogs of a direct thrombin inhibitor.
AB  - Thrombin is a serine protease that plays a key role in blood clotting.
      Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years
      ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with
      various heterocycles were prepared and evaluated for activity against thrombin,
      clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog
      6 was the most active, essentially matching the thrombin inhibitory activity of 1
      with slightly improved selectivity over trypsin. 

PMID- 24461291
TI  - Undesired versus designed enzymatic cleavage of linkers for liver targeting.
AB  - A design for the selective release of drug molecules in the liver was tested,
      involving the attachment of a representative active agent by an ester linkage to
      various 2-substituted 5-aminovaleric acid carbamates. The anticipated pathway of
      carboxylesterase-1-mediated carbamate cleavage followed by lactamization and drug
      release was frustrated by unexpectedly high sensitivity of the ester linkage
      toward hydrolysis by carboxylesterase-2 and other microsomal components. 

PMID- 24461293
TI  - Dual inhibition of HCV and HIV by ring-expanded nucleosides containing the 5:7
      fused imidazo[4,5-e][1,3]diazepine ring system. In vitro results and
      implications.
AB  - Examples of ring-expanded nucleosides (RENs), represented by general structures 1
      and 2, exhibited dual anti-HCV and anti-HIV activities in both cell culture
      systems and the respective target enzyme assays, including HCV NTPase/helicase
      and human RNA helicase DDX3. Since HCV is a leading co-infection in late stage
      HIV AIDS patients, often leading to liver cirrhosis and death, the observed dual
      inhibition of HCV and HIV by the target nucleoside analogues has potentially
      beneficial implications in treating HIV patients infected with HCV. 

PMID- 24461294
TI  - Inhibition of protein kinase C alpha/betaII and activation of c-Jun NH2-terminal
      kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung
      cancer NCI-H460 cells.
AB  - Though glycyrrhetinic acid (GA) from Glycyrrhiza glabra was known to exert
      antioxidant, antifilarial, hepatoprotective, anti-inflammatory and anti-tumor
      effects, the antitumor mechanism of GA was not clearly elucidated in non-small
      cell lung cancer cells (NSCLCCs). Thus, in the present study, the underlying
      apoptotic mechanism of GA was examined in NCI-H460 NSCLCCs. GA significantly
      suppressed the viability of NCI-H460 and A549 non-small lung cancer cells. Also,
      GA significantly increased the sub G1 population by cell cycle analysis and
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive
      cells in a concentration dependent manner in NCI-H460 non-small lung cancer
      cells. Consistently, GA cleaved poly (ADP-ribosyl) polymerase (PARP), caspase
      9/3, attenuated the expression of Bcl-XL, Bcl-2, Cyclin D1 and Cyclin E in NCI
      H460 cells. Interestingly, GA attenuated the phosphorylation of protein kinase C
      (PKC) alpha/betaII and extracellular activated protein kinase (ERK) as well as
      activated the phosphorylation of PKC delta and c-Jun NH2-terminal kinase in NCI
      H460 cells. Conversely, PKC promoter phorbol 12-myristate 13-acetate (PMA) and
      JNK inhibitor SP600125 reversed the cleavages of caspase 3 and PARP induced by GA
      in NCI-H460 cells. Overall, our findings suggest that GA induces apoptosis via
      inhibition of PKC alpha/betaII and activation of JNK in NCI-H460 non-small lung
      cancer cells as a potent anticancer candidate for lung cancer treatment. 

PMID- 24461295
TI  - A novel class of ion displacement ligands as antagonists of the alphaIIbbeta3
      receptor that limit conformational reorganization of the receptor.
AB  - A collection of alphaIIbbeta3 integrin receptor antagonists possessing a unique
      MIDAS metal ion displacement mechanism of action is presented. Insight into these
      agents' structure-activity relationships, binding modality, and pharmacokinetic
      and pharmacodynamic profiles highlight the potential of these small molecule ion
      displacement ligands as attractive candidates for clinical development. 

PMID- 24461296
TI  - In vitro phenotypic screening of 7-chloro-4-amino(oxy)quinoline derivatives as
      putative anti-Trypanosoma cruzi agents.
AB  - In this study, a series of 22 pre-synthesized 7-chloro-4-amino(oxy)quinoline
      derivatives was assayed in vitro as potential antichagasic agents. A primary
      screening against Trypanosoma cruzi epimastigotes and a non-specific cytotoxicity
      assay on murine fibroblasts were simultaneously performed, resulting quinolines
      3, 7 and 12 with great selectivity (SI) on the extracellular parasite (SI7, SI3,
      SI12 and SIBZ >9.44). Therefore, the activity of these derivatives was evaluated
      on intracellular amastigotes, achieving derivative 7 the best SI (SI=12.73).
      These results, supported by the in silico prediction of a good oral
      bioavailability and a suitable risk profile, propose the 4-amino-7
      chloroquinoline scaffold as a potential template for designing trypanocidal
      prototypes. 

PMID- 24461297
TI  - Rat intestinal sucrase inhibition of constituents from the roots of Rosa rugosa
      Thunb.
AB  - A new octanordammarane triterpene, 3beta,15alpha-dihydroxymansumbinol (1) and a
      novel A-ring contracted oleanane triterpenoid, 2-formyl-(A)1-19alpha-hydroxy-1
      norolean-2,12-dien-28-oic acid (2) were isolated from the roots extract of Rosa
      rugosa along with fifteen known compounds (3-17). Their structures were
      elucidated by extensive spectroscopic analysis, including 1D and 2D NMR, and
      FTICRMS. The MeOH extract, as well as CH2Cl2 and EtOAc fractions at a
      concentration of 0.5mg/mL showed potent sucrase inhibitory activity, with
      inhibition percentage values of 84.67+/-5.37%, 87.50+/-2.78%, and 81.91+/-2.90%,
      respectively. In addition, compounds 7-13 (1.0 mM) showed potent sucrase
      inhibitory activity (61.88+/-3.19% to 84.70+/-3.07% inhibition), which was
      comparable to that of the positive control, acarbose, with an inhibition
      percentage value of 50.96+/-2.97%. Compounds 1, 2, 4, and 14-17 showed moderate
      and/or weak inhibitory activities at the same concentration. The alpha
      glucosidase inhibitory activities of the extracts and purified compounds may
      provide a novel opportunity to develop a new class of antidiabetic agents.

PMID- 24461298
TI  - Anion inhibition studies of two new beta-carbonic anhydrases from the bacterial
      pathogen Legionella pneumophila.
AB  - We investigated the cloning, catalytic activity and anion inhibition of the beta
      class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen
      Legionella pneumophila. Two such enzymes, lpCA1 and lpCA2, were found in the
      genome of this pathogen. These enzymes were determined to be efficient catalysts
      for CO2 hydration, with kcat values in the range of (3.4-8.3)*10(5) s(-1) and
      kcat/KM values of (4.7-8.5)*10(7) M(-1) s(-1). A set of inorganic anions and
      small molecules was investigated to identify inhibitors of these enzymes.
      Perchlorate and tetrafluoroborate were not acting as inhibitors (KI >200 mM),
      whereas sulfate was a very weak inhibitor for both lpCA1 and lpCA2 (KI values of
      77.9-96.5 mM). The most potent lpCA1 inhibitors were cyanide, azide, hydrogen
      sulfide, diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid and
      phenylarsonic acid, with KI values ranging from 6 to 94 MUM. The most potent
      lpCA2 inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic
      acid and phenylarsonic acid, with KI values ranging from 2 to 13 MUM. As these
      enzymes seem to be involved in regulation of phagosome pH during Legionella
      infection, inhibition of these targets may lead to antibacterial agents with a
      novel mechanism of action.

PMID- 24461299
TI  - Anilino-monoindolylmaleimides as potent and selective JAK3 inhibitors.
AB  - We designed a series of anilino-indoylmaleimides based on structural elements
      from literature JAK3 inhibitors 3 and 4, and our lead 5. These new compounds were
      tested as inhibitors of JAKs 1, 2 and 3 and TYK2 for therapeutic intervention in
      rheumatoid arthritis (RA). Our requirements, based on current scientific
      rationale for optimum efficacy against RA with reduced side effects, was for
      potent, mixed JAK1 and 3 inhibition, and selectivity over JAK2. Our efforts
      yielded a potent JAK3 inhibitor 11d and its eutomer 11e. These compounds were
      highly selective for inhibition of JAK3 over JAK2 and TYK. The compounds
      displayed only modest JAK1 inhibition. 

PMID- 24461300
TI  - Prognostic factors in the radical nonsurgical treatment of stage IIIB non-small
      cell lung cancer.
AB  - BACKGROUND: Many patients diagnosed with stage IIIB (AJCC sixth edition; T4, N3,
      or both; no pleural effusion) non-small-cell lung cancer (NSCLC) are treated with
      curative intent, despite a low cure rate. Guidelines are required to help select
      patients for radical therapy so that the patients with little chance of cure may
      be spared the toxicities of aggressive treatment. A retrospective analysis was
      performed to investigate factors influencing outcomes in these patients.
      MATERIALS AND METHODS: From 2002 to 2009, all cases of stage IIIB NSCLC from the
      authors' institution were identified. Patients treated with radical radiotherapy
      (minimum dose, 50 Gy), with or without chemotherapy, were included. Charts were
      reviewed for patient demographic data, baseline blood work, tumor factors,
      treatment factors, and hospitalizations. The primary outcome was overall survival
      (OS), measured from time of diagnosis. RESULTS: Of 238 patients identified, 184
      eligible cases were reviewed. The median follow-up for all patients was 17.2
      months (range, 1.7-237.1). The median progression-free survival was 10.8 months
      (95% CI, 9.6-12.4). Median survival was 17.9 months, and OS was 68%, 42%, and 28%
      at 1, 2, and 3 years, respectively. In multivariate analysis, female gender
      (hazard ratio [HR], 0.58; 95% CI, 0.37-0.88; P = .0013), <= 5% weight loss (HR,
      0.64; 95% CI, 0.43-0.93; P = .01), and absence of N3 disease (HR, 0.64; 95% CI,
      0.42-0.96; P = .03) were associated with significantly longer survival.
      CONCLUSION: OS was significantly longer in women, in patients with <= 5% weight
      loss, and in those without N3 disease. Good patient selection remains important
      in the radical treatment of stage IIIB NSCLC.

PMID- 24461301
TI  - Systematic review with meta-analysis: the haemodynamic effects of carvedilol
      compared with propranolol for portal hypertension in cirrhosis.
AB  - BACKGROUND: Propranolol is recommended for prophylaxis of variceal bleeding in
      cirrhosis. Carvedilol is a nonselective beta-blocker with a mild anti-alfa-1
      adrenergic activity. Several studies have compared carvedilol and propranolol,
      yielding inconsistent results. AIM: To perform a systematic review and meta
      analysis of the randomised clinical trials comparing carvedilol with propranolol
      for hepatic vein pressure gradient reduction. METHODS: Studies were searched on
      the MEDLINE, EMBASE and Cochrane library databases up to November 2013. The
      weighted mean difference in percent hepatic vein pressure gradient reduction and
      the relative risk of failure to achieve a hemodynamic response (reduction >=20%
      of baseline or to <=12 mmHg) with each drug were used as measures of treatment
      efficacy. RESULTS: Five studies (175 patients) were included. Indication to
      treatment was primary prophylaxis of variceal bleeding in 76% of patients. There
      were overall three acute (60-90 min after drug administration) and three long
      term (after 7-90 days of therapy) comparisons. The summary mean weighted
      difference in % of reduction in hepatic vein pressure gradient was: acute -7.70
      (CI -12.40, -3.00), long-term -6.81 (CI -11.35, -2.26), overall -7.24 (CI -10.50,
      -3.97), favouring carvedilol. The summary relative risk of failure to achieve a
      hemodynamic response with carvedilol was 0.66 (CI 0.44, 1.00). Adverse events
      were nonsignificantly more frequent and serious with carvedilol. However, quality
      of trials was mostly unsatisfactory. CONCLUSIONS: Carvedilol reduces portal
      hypertension significantly more than propranolol. However, available data do not
      allow a satisfactory comparison of adverse events. These results suggest a
      potential for a cautious clinical use.

PMID- 24461302
TI  - [The Review of Neurology exists since 1883 and is therefore 130 years old, a more
      than respectable age that should not represent a brake to evolution and change].

PMID- 24461303
TI  - The impact of intracytoplasmic mucin in lung adenocarcinoma with pneumonic
      radiological presentation.
AB  - OBJECTIVES: This study investigated the clinical and prognostic impact of
      intracytoplasmic mucin in lung adenocarcinoma with "pneumonic" radiological
      presentation, formerly known as bronchioloalveolar carcinoma (BAC). PATIENTS AND
      METHODS: Between 1986 and 2011, clinical and pathological data from 120
      consecutive patients with lung adenocarcinoma with "pneumonic" radiological
      presentation were reviewed. Intracytoplasmic mucin was assessed using a diastase
      resistant periodic acid-Schiff staining. The presence of EGFR or K-Ras mutations
      and ALK rearrangement were determined in surgical samples. RESULTS: The two
      predominant histological patterns were invasive mucinous adenocarcinoma (40%) and
      lepidic predominant adenocarcinoma (32%). Intracytoplasmic mucin was detected in
      71 patients (59.2%) who were more likely to be non-smokers (p=0.04) and have
      bronchorrhea (p=0.006), crepitant rales (p=0.02), or neutrophil alveolitis
      (p=0.0004). In mucin-producing tumors, EGFR mutation was not detected, K-Ras
      mutations and ALK rearrangement were present in 32% and 3% of cases,
      respectively. In non-mucin-producing tumors, EGFR and K-Ras mutations were
      detected in 17% and 10% of cases, respectively, no ALK rearrangement was
      detected. In univariate analysis, performance status>0, crepitant rales,
      bronchorrhea, neutrophil alveolitis, bilateral extension, intracytoplasmic mucin
      and no surgery were associated with worse survival. In multivariate analyses,
      intracytoplasmic mucin, neutrophil alveolitis, and no surgery were independent
      factors for worse survival. CONCLUSION: Intracytoplasmic mucin is associated with
      specific clinical characteristics and is an independent factor for worse survival
      in lung adenocarcinoma formerly known as BAC.

PMID- 24461304
TI  - Pleural epithelioid hemangioendothelioma harboring CAMTA1 rearrangement.
AB  - Pleural epithelioid hemangioendothelioma (EHE) is a very rare disease with
      adverse clinical outcomes. Recently, CAMTA1 rearrangement has been introduced as
      a consistent genetic abnormality in EHEs of different anatomical locations. We
      report a 71-year-old man with pleural EHE harboring CAMTA1 rearrangement
      confirmed by fluorescence in situ hybridization on paraffin embedded tissue. 

PMID- 24461305
TI  - Adolescents' multiple, recurrent subjective health complaints: investigating
      associations with emotional/behavioural difficulties in a cross-sectional, school
      based study.
AB  - BACKGROUND: Adolescence has been documented as the peak age of onset for mental
      health perturbations, clinical disorders and unsubstantiated health complaints.
      The present study attempted to investigate associations between multiple,
      recurrent subjective health complaints (SHC) with emotional/behavioural
      difficulties, as measured by the Strengths and Difficulties Questionnaire scale
      (SDQ), among Greek adolescents. METHODS: Questionnaires were administered in a
      large, nation-wide, random, school-based sample of Greek adolescents, aged 12-18
      years. Data from 1170 participants were analyzed. Adolescents with multiple,
      recurrent SHC were compared in terms of their emotional/behavioural difficulties
      to their peers with lower levels of health complaints. SDQ scales were separately
      investigated for their associations with multiple, recurrent SHC, after
      adjustment for gender, age and socioeconomic status (ses). Further analysis
      included multiple logistic regression models with multiple, recurrent SHC as the
      dependent variable and gender, age, ses and SDQ Total difficulties score as
      independent factors. Potential gender and age interactions were also explored.
      RESULTS: Almost half of the study participants reported multiple, recurrent SHC.
      Adolescents with multiple, recurrent SHC had higher scores on all SDQ scales,
      except from the Prosocial behavior scale, compared to their peers with lower
      levels of health complaints. Emotional Symptoms, Conduct Problems,
      Hyperactivity/Inattention and Peer Problems were associated with greater
      likelihood of having multiple, recurrent SHC, after adjustment for gender, age
      and ses. The multiple logistic regression models revealed that older adolescents
      and girls, as well as those with increased Total difficulties score had an
      increased risk for multiple, recurrent SHC reporting. No significant interaction
      between SDQ scales and gender or age was found. CONCLUSIONS: Our study highlights
      the magnitude of psychological burden among adolescents experiencing multiple,
      recurrent SHC. Professionals in school and clinical settings should be cautious
      for impaired emotional/behavioural functioning when assessing adolescents with
      multiple, recurrent SHC, so as early identification of at-risk individuals and
      timely, appropriate referrals are facilitated.

PMID- 24461306
TI  - Sustained high incidence of injuries from burns in a densely populated urban slum
      in Kenya: an emerging public health priority.
AB  - INTRODUCTION: Ninety-five percent of burn deaths occur in low- and middle-income
      countries (LMICs); however, longitudinal household-level studies have not been
      done in urban slum settings, where overcrowding and unsafe cook stoves may
      increase likelihood of injury. METHODS: Using a prospective, population-based
      disease surveillance system in the urban slum of Kibera in Kenya, we examined the
      incidence of household-level burns of all severities from 2006-2011. RESULTS: Of
      approximately 28,500 enrolled individuals (6000 households), we identified 3072
      burns. The overall incidence was 27.9/1000 person-years-of-observation. Children
      <5 years old sustained burns at 3.8-fold greater rate compared to (p<0.001) those
      >=5 years old. Females >=5 years old sustained burns at a rate that was 1.35-fold
      (p<0.001) greater than males within the same age distribution. Hospitalizations
      were uncommon (0.65% of all burns). CONCLUSIONS: The incidence of burns, 10-fold
      greater than in most published reports from Africa and Asia, suggests that such
      injuries may contribute more significantly than previously thought to morbidity
      in LMICs, and may be increased by urbanization. As migration from rural areas
      into urban slums rapidly increases in many African countries, characterizing and
      addressing the rising burden of burns is likely to become a public health
      priority.

PMID- 24461307
TI  - Better tests of consciousness are needed, but skepticism about unconscious
      processes is unwarranted.
AB  - What people report is, at times, the best evidence we have for what they
      experience. Newell & Shanks (N&S) do a service for debates regarding the role of
      unconscious influences on decision making by offering some sound methodological
      recommendations. We doubt, however, that those recommendations go far enough. For
      even if people have knowledge of the factors that influence their decisions, it
      does not follow that such knowledge is conscious, and plays a causal role, at the
      time the decision is made. Moreover, N&S fail to demonstrate that unconscious
      thought plays no role at all in decision making. Indeed, such a claim is quite
      implausible. In making these points we comment on their discussion of the
      literature on expertise acquisition and the Iowa Gambling Task. 

PMID- 24461308
TI  - Maybe it helps to be conscious, after all.
AB  - Psychologists debate whether consciousness or unconsciousness is most central to
      human behavior. Our goal, instead, is to figure out how they work together.
      Conscious processes are partly produced by unconscious processes, and much
      information processing occurs outside of awareness. Yet, consciousness has
      advantages that the unconscious does not. We discuss how consciousness causes
      behavior, drawing conclusions from large-scale literature reviews. 

PMID- 24461309
TI  - Evidence of an association between 10/10 genotype of DAT1 and endophenotypes of
      attention deficit/hyperactivity disorder.
AB  - INTRODUCTION: Genetic variance of attention deficit-hyperactivity disorder (ADHD)
      is a strong determinant of this disorder. The 40 base pairs (bp) variable number
      tandem repeat (VNTR) located in the 3' untranslated region (UTR) of DAT1 gene
      increases the expression of the dopamine transporter. Therefore, DAT1 has been
      associated with susceptibility to ADHD. OBJECTIVE: To determine the association
      between the VNTR of DAT1 and the phenotype of ADHD or its endophenotypes in a
      sample of children aged between 6 and 15 years from Bogota. SUBJECTS AND METHODS:
      We selected 73 patients with ADHD and 54 controls. WISC test was applied in all
      subjects and executive functions were assessed. The VNTR of DAT1 was polymerase
      chain reaction-amplified. Data regarding population genetics and statistical
      analysis were obtained. Correlation and association tests between genotype and
      neuropsychological testing were performed. RESULTS: The DAT1 polymorphism was not
      associated with ADHD (P=.85). Nevertheless, the 10/10 genotype was found to be
      correlated with the processing speed index (P<.05). In the hyperactivity subtype,
      there was a genotypic correlation with some subtests of executive function
      (cognitive flexibility) (P<=.01). In the combined subtype, the 10/10 genotype was
      associated with verbal comprehension index of WISC (P<.05). CONCLUSIONS: A
      correlation was found between DAT1 VNTR and the subtest "processing speed index"
      of WISC and the subtest "cognitive flexibility" of executive functions. To our
      knowledge, this is the first report to assess DAT1 gene in a Colombian
      population.

PMID- 24461310
TI  - Review of nutrient actions on age-related macular degeneration.
AB  - The actions of nutrients and related compounds on age-related macular
      degeneration (AMD) are explained in this review. The findings from 80 studies
      published since 2003 on the association between diet and supplements in AMD were
      reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility
      include carotenoids (lutein and zeaxanthin, beta-carotene), vitamins (vitamin A,
      E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids
      [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA
      and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary
      carbohydrates. The literature revealed that many of these antioxidants and
      nutrients exert a protective role by functioning synergistically. Specifically,
      the use of dietary supplements with targeted actions can provide minimal benefits
      on the onset or progression of AMD; however, this does not appear to be
      particularly beneficial in healthy people. Furthermore, some supplements or
      nutrients have demonstrated discordant effects on AMD in some studies. Since
      intake of dietary supplements, as well as exposure to damaging environmental
      factors, is largely dependent on population habits (including dietary practices)
      and geographical localization, an overall healthy diet appears to be the best
      strategy in reducing the risk of developing AMD. As of now, the precise mechanism
      of action of certain nutrients in AMD prevention remains unclear. Thus, future
      studies are required to examine the effects that nutrients have on AMD and to
      determine which factors are most strongly correlated with reducing the risk of
      AMD or preventing its progression. 

PMID- 24461311
TI  - Mechanisms underlying the antihypertensive effects of garlic bioactives.
AB  - Cardiovascular disease remains the leading cause of death worldwide with
      hypertension being a major contributing factor to cardiovascular disease
      associated mortality. On a population level, non-pharmacological approaches, such
      as alternative/complementary medicine, including phytochemicals, have the
      potential to ameliorate cardiovascular risk factors, including high blood
      pressure. Several epidemiological studies suggest an antihypertensive effect of
      garlic (Allium sativum) and of many its bioactive components. The aim of this
      review is to present an in-depth discussion regarding the molecular, biochemical
      and cellular rationale underlying the antihypertensive properties of garlic and
      its bioactive constituents with a primary focus on S-allyl cysteine and allicin.
      Key studies, largely from PubMed, were selected and screened to develop a
      comprehensive understanding of the specific role of garlic and its bioactive
      constituents in the management of hypertension. We also reviewed recent advances
      focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in
      modulating various parameters implicated in the pathogenesis of hypertension.
      These parameters include oxidative stress, nitric oxide bioavailability, hydrogen
      sulfide production, angiotensin converting enzyme activity, expression of nuclear
      factor-kappaB and the proliferation of vascular smooth muscle cells. This review
      suggests that garlic and garlic derived bioactives have significant medicinal
      properties with the potential for ameliorating hypertension and associated
      morbidity; however, further clinical and epidemiological studies are required to
      determine completely the specific physiological and biochemical mechanisms
      involved in disease prevention and management. 

PMID- 24461313
TI  - Krill oil supplementation lowers serum triglycerides without increasing low
      density lipoprotein cholesterol in adults with borderline high or high
      triglyceride levels.
AB  - The aim of the study was to explore the effects of 12 weeks daily krill oil
      supplementation on fasting serum triglyceride (TG) and lipoprotein particle
      levels in subjects whose habitual fish intake is low and who have borderline high
      or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil
      lowers serum TG levels in subjects with borderline high or high fasting TG
      levels. To test our hypothesis 300 male and female subjects were included in a
      double-blind, randomized, multi-center, placebo-controlled study with five
      treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil.
      Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks.
      Due to a high intra-individual variability in TG levels, data from all subjects
      in the four krill oil groups were pooled to increase statistical power, and a
      general time- and dose-independent one-way analysis of variance was performed to
      assess efficacy. Relative to subjects in the placebo group, those administered
      krill oil had a statistically significant calculated reduction in serum TG levels
      of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups
      relative to the placebo group. The outcome of the pooled analysis suggests that
      krill oil is effective in reducing a cardiovascular risk factor. However, owing
      to the individual fluctuations of TG concentrations measured, a study with more
      individual measurements per treatment group is needed to increase the confidence
      of these findings. 

PMID- 24461312
TI  - S-(-)equol producing status not associated with breast cancer risk among low
      isoflavone-consuming US postmenopausal women undergoing a physician-recommended
      breast biopsy.
AB  - Soy foods are the richest sources of isoflavones, mainly daidzein and genistein.
      Soy isoflavones are structurally similar to the steroid hormone 17beta-estradiol
      and may protect against breast cancer. S-(-)equol, a metabolite of the soy
      isoflavone daidzein, has a higher bioavailability and greater affinity for
      estrogen receptor beta than daidzein. Approximately one-third of the Western
      population is able to produce S-(-)equol, and the ability is linked to certain
      gut microbes. We hypothesized that the prevalence of breast cancer, ductal
      hyperplasia, and overall breast pathology will be lower among S-(-)equol
      producing, as compared with nonproducing, postmenopausal women undergoing a
      breast biopsy. We tested our hypothesis using a cross-sectional study design.
      Usual diets of the participants were supplemented with 1 soy bar per day for 3
      consecutive days. Liquid chromatography-multiple reaction ion monitoring mass
      spectrometry analysis of urine from 143 subjects revealed 25 (17.5%) as S-(
      )equol producers. We found no statistically significant associations between S-(
      )equol producing status and overall breast pathology (odds ratio [OR], 0.68; 95%
      confidence interval [CI], 0.23-1.89), ductal hyperplasia (OR, 0.84; 95% CI, 0.20
      3.41), or breast cancer (OR, 0.56; 95% CI, 0.16-1.87). However, the mean dietary
      isoflavone intake was much lower (0.3 mg/d) than in previous reports. Given that
      the amount of S-(-)equol produced in the gut depends on the amount of daidzein
      exposure, the low soy intake coupled with lower prevalence of S-(-)equol
      producing status in the study population favors toward null associations.
      Findings from our study could be used for further investigations on S-(-)equol
      producing status and disease risk. 

PMID- 24461314
TI  - Knowledge, perceptions, and behaviors of adults concerning nonalcoholic beverages
      suggest some lack of comprehension related to sugars.
AB  - Key recommendations in the 2010 Dietary Guidelines for Americans and US
      Department of Agriculture's MyPlate are to reduce the intake of added sugars,
      particularly from sugar-sweetened beverages, and drink water instead of "sugary"
      beverages. However, little is known about consumer knowledge, perceptions, and
      behaviors regarding sugars in beverages. We hypothesized that consumers would
      have limited or inaccurate knowledge of the sugars in beverages and that their
      beverage consumption behaviors would not reflect their primary concerns related
      to sugars in beverages. An online survey was completed by 3361 adults 18 years
      and older residing throughout the United States. Water was consumed in the
      highest amounts followed by (in descending amounts) other beverages (includes
      coffee and tea), added sugar beverages, milk, diet drinks, and 100% fruit juice
      and blends. Participants primarily associated the term "sugary" with beverages
      containing added sugars; however, almost 40% identified 100% fruit juice as
      sugary. Some participants misidentified the types of sugars in beverages,
      particularly with respect to milk and 100% fruit juices. Generally, beverage
      choices were consistent with stated concerns about total, added, or natural
      sugars; however, less than 40% of participants identified added sugars as a
      primary concern when choosing beverages despite public health recommendations to
      reduce the intake of added sugars and sugar-sweetened beverages. Results suggest
      that there may be a considerable level of consumer misunderstanding or confusion
      about the types of sugars in beverages. More consumer research and education are
      needed with the goal of helping consumers make more informed and healthy beverage
      choices. 

PMID- 24461315
TI  - Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin
      resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver
      disease patients.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of hepatic
      injury in the world. One of the most important therapeutic strategies for this
      disease is modulating insulin resistance and oxidative stress. In this study, we
      investigated the hypothesis that supplementation with cinnamon exerts an insulin
      sensitizer effect in patients with NAFLD. In a double-blind, placebo-controlled
      trial with two parallel groups, fifty patients with NAFLD were randomized to
      receive daily supplementation with either two capsules of cinnamon (each capsule
      contain 750 mg cinnamon) or 2 placebo capsules, daily for 12 weeks. During the
      intervention, all patients were given advice on how to implement a balanced diet
      and physical activity into their daily lives. In the treatment group (P < .05),
      significant decreases in HOMA (Homeostatic Model Assessment) index, FBS (fasting
      blood glucose), total cholesterol, triglyceride, ALT (alanine aminotransferase),
      AST (aspartate aminotransferase), GGT (gamma glutamine transpeptidase), and high
      sensitivity C-reactive protein were seen, but there was no significant change in
      serum high-density lipoproteins levels (P = .122). In both groups, low-density
      lipoproteins decreased significantly (P < .05). In conclusion, the study suggests
      that taking 1500 mg cinnamon daily may be effective in improving NAFLD
      characteristics. 

PMID- 24461316
TI  - Vitamin E, vitamin A, and zinc status are not related to serologic response to
      influenza vaccine in older adults: an observational prospective cohort study.
AB  - It has been hypothesized that micronutrient levels play a role in the immune
      response to vaccination; however, population-level research on the association
      between micronutrient levels and immune response to influenza vaccination is
      needed. In this study, we hypothesized that decreasing levels of nutrients would
      be associated with decreased hemagglutination inhibition (HAI) responses to
      influenza vaccination. Therefore, the purpose of this study was to determine
      whether serum vitamin A, vitamin E, or zinc levels are associated with influenza
      vaccine response determined by HAI titer in adults 65 years or older.
      Participants in this study included 205 community-dwelling adults 65 years or
      older who resided in Marshfield, WI, USA, from fall 2008 through spring 2009.
      Participants received trivalent influenza vaccine and donated blood samples
      before and 21 to 28 days after vaccination. Prevaccination levels of serum
      retinol, alpha-tocopherol, and zinc as well as prevaccination and postvaccination
      HAI titer levels were measured. No participants were vitamin A or vitamin E
      deficient; 20% had low serum zinc levels (<70 MUg/dL). Continuous variables and
      categorical quartiles coding for vitamin A, vitamin E, and zinc levels were not
      related to prevaccination or postvaccination seroprotection or seroconversion for
      any of the vaccine components (influenza A [H1N1], A [H3N2], or B), after
      adjusting for age, sex, body mass index, and prevaccination HAI geometric mean
      titer. In conclusion, our study population showed no association between
      variations in levels of serum vitamin A, vitamin E, or zinc and influenza vaccine
      response as measured by HAI in adults older than 65 years. Thus, associations
      between micronutrients and other measures of vaccine response, such as cell
      mediated immune parameters, should also be explored. 

PMID- 24461317
TI  - Coffee polyphenols improve peripheral endothelial function after glucose loading
      in healthy male adults.
AB  - Brewed coffee is a widely consumed beverage, and many studies have examined its
      effects on human health. We investigated the vascular effects of coffee
      polyphenols (CPPs), hypothesizing that a single ingestion of CPP during glucose
      loading would improve endothelial function. To test this hypothesis, we conducted
      a randomized acute clinical intervention study with crossover design and measured
      reactive hyperemia index (RHI) to assess the acute effects of a 75-g glucose load
      with CPP in healthy, nondiabetic adult men. Blood glucose and insulin levels were
      elevated after glucose loading with and without CPP, with no significant
      differences between treatments. The RHI did not significantly decrease after
      glucose loading without CPP. With CPP, however, RHI significantly (P < .05)
      increased over baseline after glucose loading. The difference between treatments
      was statistically significant (P < .05). No significant changes were observed in
      an oxidative stress marker after glucose loading with or without CPP. These
      findings suggest that a single ingestion of CPP improves peripheral endothelial
      function after glucose loading in healthy subjects. 

PMID- 24461318
TI  - Soy beta-conglycinin improves glucose uptake in skeletal muscle and ameliorates
      hepatic insulin resistance in Goto-Kakizaki rats.
AB  - Although the underlying mechanism is unclear, beta-conglycinin (betaCG), the
      major component of soy proteins, regulates blood glucose levels. Here, we
      hypothesized that consumption of betaCG would normalize blood glucose levels by
      ameliorating insulin resistance and stimulating glucose uptake in skeletal
      muscles. To test our hypothesis, we investigated the antidiabetic action of
      betaCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed
      that plasma adiponectin levels and adiponectin receptor 1 messenger RNA
      expression in skeletal muscle were higher in betaCG-fed rats than in casein-fed
      rats. Phosphorylation of adenosine monophosphate-activated protein kinase (AMP
      kinase) but not phosphatidylinositol-3 kinase was activated in betaCG-fed GK
      rats. Subsequently, betaCG increased translocation of glucose transporter 4 to
      the plasma membrane. Unlike the results in skeletal muscle, the increase in
      adiponectin receptor 1 did not lead to AMP kinase activation in the liver of
      betaCG-fed rats. The down-regulation of sterol regulatory element-binding factor
      1, which is induced by low insulin levels, promoted the increase in hepatic
      insulin receptor substrate 2 expression. Based on these findings, we concluded
      that consumption of soy betaCG improves glucose uptake in skeletal muscle via AMP
      kinase activation and ameliorates hepatic insulin resistance and that these
      actions may help normalize blood glucose levels in GK rats. 

PMID- 24461319
TI  - The potential of cod hydrolyzate to inhibit blood pressure in spontaneously
      hypertensive rats.
AB  - Hypertension is an independent yet controllable risk factor for cardiovascular
      diseases. Synthetic angiotensin-converting enzyme (ACE) inhibitors used to treat
      hypertension are often associated with adverse effects, and the interest in diet
      related inhibitors is increasing. We hypothesized that North Atlantic fish
      hydrolysate might inhibit ACE, thus preventing hypertension. We assessed the ACE
      inhibitory potential of various North Atlantic fish species and evaluated the
      effect of dietary supplementation of fish hydrolysates on the blood pressure of
      spontaneously hypertensive rats. Fish samples were hydrolyzed using simulated
      gastrointestinal digestion, and ACE inhibitory activity was evaluated using an
      ACE inhibitory activity assay. In vivo anti-hypertensive effects were evaluated
      by administering hydrolysates of wild Atlantic cod (Gadus morhua L.), haddock
      (Melanogrammus aeglefinus L.), or farmed Atlantic salmon (Salmo salar L.) to 10
      week-old male, spontaneously hypertensive rats for 4 weeks. The dosing was 200
      mg/kg body weight for 21 days, followed by 500 mg/kg body weight for 7 days.
      Water and Captopril (20 mg/kg body weight) were administered as the negative and
      positive controls, respectively. The analyzed fish hydrolysates exhibited a 50%
      ACE inhibition coefficient (IC50) of 1 to 2.7 MUg/mU ACE. Fish hydrolysate
      supplements did not significantly inhibit the increase in blood pressure during
      the experimental period. The group receiving cod supplement had a lower (not
      significant) increase in blood pressure compared to the other groups. Although
      further studies are necessary to verify the antihypertensive effect of cod, the
      results obtained in this study indicate the potential that cod hydrolysate may
      have in inhibiting hypertension.

PMID- 24461320
TI  - Greater weight loss among men participating in a commercial weight loss program:
      a pooled analysis of 2 randomized controlled trials.
AB  - Being overweight and obese are significant health concerns for men and women, yet
      despite comparable needs for effective weight loss and maintenance strategies,
      little is known about the success of commercial weight loss programs in men. This
      study tests the hypothesis that men participating in a commercial weight loss
      program (Weight Watchers) had significantly greater weight loss than men
      receiving limited support from health professionals for weight loss (controls). A
      pooled analysis of weight loss and related physiologic parameter data from 2
      randomized clinical trials was conducted. After 12 months, analysis of covariance
      tests showed that men in the commercial program group (n = 85) lost significantly
      more weight (P < .01) than men in the control group (n = 84); similar significant
      differences were observed for body mass index and waist circumference. These
      results suggest that participation in a commercial weight loss program may be a
      more effective means to lose weight and maintain weight loss. 

PMID- 24461321
TI  - Differential expression of pro-inflammatory and anti-inflammatory cytokines
      during experimental infection with low or high virulence bovine viral diarrhea
      virus in beef calves.
AB  - The objective was to compare the mRNA expression of pro-inflammatory (TNF-alpha,
      IL-1beta, IFN-gamma, IL-2, IL-12, IL-15) and anti-inflammatory (IL-4, IL-10, TGF
      beta) cytokines, after experimental infection with low or high virulence
      noncytopathic (ncp) bovine viral diarrhea virus (BVDV). Thirty BVDV-naive, beef
      calves were intranasally inoculated with low (LV; n=10, SD-1) or high (HV; n=10,
      1373) virulence ncp BVDV or with BVDV-free cell culture medium (Control, n=10).
      Calves were euthanized on day 5 post-inoculation, and tracheo-bronchial lymph
      node and spleen samples were collected for mRNA expression through quantitative
      RT-PCR. mRNA levels of pro-inflammatory (TNF-alpha, IL-1beta, IL-2, IFN-gamma)
      and anti-inflammatory (IL-4 and IL-10) cytokines were up-regulated in tracheo
      bronchial lymph nodes of HV, but not in LV, compared to the control group
      (P<0.05). IL-12 mRNA level was up-regulated in tracheo-bronchial lymph nodes of
      both LV and HV groups (P <= 0.05). A significant up-regulation of IL-15 mRNA was
      observed in tracheo-bronchial lymph nodes for LV calves (P<0.002), but not for HV
      calves. Experimental inoculation with BVDV-2 1373 stimulated significant mRNA
      expression of pro-inflammatory and anti-inflammatory cytokines. In contrast,
      inoculation with BVDV-1a SD-1 only resulted in up-regulation of IL-12 and IL-15
      mRNA, which is associated with activation of macrophages and NK cells during
      innate immune response.

PMID- 24461322
TI  - Hair band retained prosthetic reconstruction of bilaterally missing ears: a case
      of congenital atresia of external auditory canals and pinna.
AB  - INTRODUCTION: Auricular defects present reconstructive challenges, especially if
      they are bilateral. Surgical reconstruction provides effective results for
      defects; however for some patients surgical intervention is contraindicated. This
      case report describes an easy clinical technique to rehabilitate a patient with
      auricular defects. The prime purpose of this treatment rendered was to restore
      the lost auricular structure to the patient's satisfaction in an elegant,
      comfortable and cost effective manner. PATIENT: A thirteen year old female
      patient, who had bilaterally missing ears, was referred with a chief complaint of
      discomfort caused due to her existing hair band prosthesis and unsatisfactory
      esthetics. There was constant formation of ulcers at the site where the
      prosthesis came in contact with the skin. Considering the patient's age, ease of
      use and economic status, hair band retained ear prosthesis was selected. Silicone
      ear prostheses were fabricated on acrylic substructure to ensure fit, esthetics.
      Beneath the acrylic plates, a thin layer of soft silicone material was attached.
      The ear prostheses of both sides were connected with a metal hair band to retain.
      DISCUSSION: The newly fabricated prosthesis overcame the limitations of the
      existing one. The patient and her parents were satisfied with the results.
      CONCLUSION: The hair band retained silicone ear prosthesis is esthetic,
      economical and easy to use as a facial prosthesis. The addition of soft liner
      provided a cushion-like effect, thus reducing the formation of any ulcers due to
      pressure.

PMID- 24461323
TI  - Clinical application of removable partial dentures using thermoplastic resin-part
      I: definition and indication of non-metal clasp dentures.
AB  - This position paper proposes a definition and naming standard for removable
      partial dentures (RPDs) using thermoplastic resin, and presents a guideline for
      clinical application. A panel of 14 experts having broad experience with clinical
      application of RPDs using thermoplastic resin was selected from members of the
      Japan Prosthodontic Society. At a meeting of the panel, "non-metal clasp denture"
      was referred as the generic name of RPDs with retentive elements (resin clasps)
      made of thermoplastic resin. The panel classified non-metal clasp dentures into
      two types: one with a flexible structure that lacks a metal framework and the
      other having a rigid structure that includes a metal framework. According to
      current prosthetic principles, flexible non-metal clasp dentures are not
      recommended as definitive dentures, except for limited cases such as patients
      with a metal allergy. Rigid non-metal clasp dentures are recommended in cases
      where patients will not accept metal clasps for esthetic reasons. Non-metal clasp
      dentures should follow the same design principles as conventional RPDs using
      metal clasps. 

PMID- 24461324
TI  - Near-infrared fluorescence imaging using organic dye nanoparticles.
AB  - Near-infrared (NIR) fluorescence imaging in the 700-1000 nm wavelength range has
      been very attractive for early detection of cancers. Conventional NIR dyes often
      suffer from limitation of low brightness due to self-quenching, insufficient
      photo- and bioenvironmental stability, and small Stokes shift. Herein, we present
      a strategy of using small-molecule organic dye nanoparticles (ONPs) to
      encapsulate NIR dyes to enable efficient fluorescence resonance energy transfer
      to obtain NIR probes with remarkably enhanced performance for in vitro and in
      vivo imaging. In our design, host ONPs are used as not only carriers to trap and
      stabilize NIR dyes, but also light-harvesting agent to transfer energy to NIR
      dyes to enhance their brightness. In comparison with pure NIR dyes, our organic
      dye nanoparticles possess almost 50-fold increased brightness, large Stokes
      shifts (~250 nm) and dramatically enhanced photostability. With surface
      modification, these NIR-emissive organic nanoparticles have water-dispersity and
      size- and fluorescence- stability over pH values from 2 to 10 for almost 60 days.
      With these superior advantages, these NIR-emissive organic nanoparticles can be
      used for highly efficient folic-acid aided specific targeting in vivo and ex vivo
      cellular imaging. Finally, during in vivo imaging, the nanoparticles show
      negligible toxicity. Overall, the results clearly display a potential application
      of using the NIR-emissive organic nanoparticles for in vitro and in vivo imaging.

PMID- 24461325
TI  - Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin
      functionalized nanoparticle formulation for targeted delivery of anticancer
      drugs.
AB  - Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has
      become one of the most important strategies in drug targeting. We have developed
      in our previous work nanoparticles of a mixture of two vitamin E TPGS based
      copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for
      targeted delivery of anticancer drugs such as docetaxel to the cancer cells of
      human epidermal growth factor receptor 2 (HER2) overexpression. In this research,
      we investigated the effects of the PEG chain length in TPGS, which is in fact a
      PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug
      formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend
      (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of
      molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation
      method and characterized for their size and size distribution, drug loading,
      surface morphology, surface charge and surface chemistry as well as in vitro drug
      release profile, cellular uptake and cytotoxicity. We found among such
      nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length,
      could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more
      efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in
      cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH
      blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer
      cells which are of high HER2 overexpression. We provided a theoretical
      explanation from surface mechanics and thermodynamics for endocytosis of
      nanoparticles.

PMID- 24461326
TI  - Deciphering the mechanism of protein interaction with silk fibroin for drug
      delivery systems.
AB  - Silk fibroin (SF) is an exceptional drug delivery carrier with respect to
      stabilizing, protecting, and delivering sensitive biologics. A synopsis of
      thermodynamic, static light scattering, hydrophobicity probing, and nanoparticle
      tracking analyses served as a basis to decipher the mechanism of interaction
      between SF and two model proteins, protamine and polylysine. The impact of salts
      aiding (chaotropic), not affecting (neutral), or opposing (cosmotropic) SF
      unfolding was a major determinant, ranging from complete abolishment to maximal
      interaction efficacy. Evidence is provided, that the underlying mechanism of the
      remarkable ability to tailor drug/SF interaction throughout such large ranges and
      by appropriate salt selection is the control of structural breakdown of SF
      micelles as present in pure SF ad initium. This study provides a mechanistically
      justified and hypothesis driven blueprint for future experimental designs
      addressing the controlled interaction of biologics and SF. 

PMID- 24461327
TI  - Comparative decellularization and recellularization of normal versus
      emphysematous human lungs.
AB  - Acellular whole human lung scaffolds represent a unique opportunity for ex vivo
      tissue engineering. However, it remains unclear whether lungs from individuals
      with chronic lung diseases such as chronic obstructive pulmonary disease (COPD)
      can be appropriately decellularized and recellularized. To assess this, cadaveric
      human lungs from normal (non-smoking) patients and from patients with COPD
      (smoking history) were decellularized and found by histochemical and
      immunohistochemical staining, electron microscopy, and mass spectrometry to
      retain characteristic histological architecture and extracellular matrix
      components (ECM) reflecting either normal or COPD, particularly emphysematous,
      origin. Inoculation of human bronchial epithelial cells, endothelial progenitor
      cells, bone marrow-derived mesenchymal stem cells, and lung fibroblasts via
      airway or vascular routes into small, excised segments of the decellularized
      lungs demonstrated that normal lung scaffolds robustly supported initial
      engraftment and growth of each cell type for up to one month. In contrast,
      despite initial binding, all cell types inoculated into decellularized
      emphysematous lungs did not survive beyond one week. However, cell attachment and
      proliferation on solubilized ECM homogenates of decellularized normal and
      emphysematous lungs coated onto tissue culture plates was comparable and not
      impaired, suggesting that the 3-dimensional decellularized emphysematous
      scaffolds may lack the necessary ECM architecture to support sustained cell
      growth.

PMID- 24461328
TI  - Cell based metabolic barriers to glucose diffusion: macrophages and continuous
      glucose monitoring.
AB  - It is assumed that MQ are central to glucose sensor bio-fouling and therefore
      have a major negative impact on continuous glucose monitoring (CGM) performance
      in vivo. However to our knowledge there is no data in the literature to directly
      support or refute this assumption. Since glucose and oxygen (O2) are key to
      glucose sensor function in vivo, understanding and controlling glucose and O2
      metabolic activity of MQ is likely key to successful glucose sensor performance.
      We hypothesized that the accumulation of MQ at the glucose sensor-tissue
      interface will act as "Cell Based Metabolic Barriers" (CBMB) to glucose diffusing
      from the interstitial tissue compartment to the implanted glucose sensor and as
      such creating an artificially low sensor output, thereby compromising sensor
      function and CGM. Our studies demonstrated that 1) direct injections of MQ at in
      vivo sensor implantation sites dramatically decreased sensor output (measured in
      nA), 2) addition of MQ to glucose sensors in vitro resulted in a rapid and
      dramatic fall in sensor output and 3) lymphocytes did not affect sensor function
      in vitro or in vivo. These data support our hypothesis that MQ can act as
      metabolic barriers to glucose and O2 diffusion in vivo and in vitro.

PMID- 24461329
TI  - Evaluation of antiproliferative and antimetastatic effects of heparin and
      erythropoietin on B16f10 melanoma cell line.
AB  - A number of chemotherapeutic agents and treatment strategies have been developed
      or designed to treat cancer patients. However, chemotherapeutic regimens
      frequently cause side-effects, one of which is anemia, a severe clinical problem
      for cancer patients. Erythropoietin is commonly used to treat anemia and reduce
      blood transfusions in cancer patients. Another agent which has potential use in
      cancer therapy is heparin, a glycosaminoglycan with a negative charge, known to
      increase the clearance of tumor cells from the blood in mice and also has anti
      metastatic effects. In this current study, we investigated the effects of rEpo
      and heparin either as single agents or in combination on B16F10 melanoma cells.
      Contrary to our expectations based on the previous in vitro and in vivo studies,
      we have not found a significant growth-promoting effect of rEpo on B16F10 cells.
      We have also not observed a significant cytotoxic effect of heparin on B16F10
      melanoma cell as assayed by MTT test (p > 0.05). However, heparin did
      significantly prevent the migration/proliferation of B16F10 cell in the wound
      assay as compared to the control cells after 24 h of incubation (p < 0.001). In
      addition, this effect of heparin was not prevented when rEpo was present in the
      medium in the wound assay (p < 0.01 as compared to the control). These results
      suggest that heparin may have a therapeutic potential as an anti-metastatic drug
      for cancer.

PMID- 24461330
TI  - Curcumin reduces oxidative damage by increasing reduced glutathione and
      preventing membrane permeability transition in isolated brain mitochondria.
AB  - Mitochondria are critical regulators of energy metabolism and programmed cell
      death pathways. Mitochondria are also the major site for the production of
      reactive oxygen species which make this organelle more susceptible to oxidative
      damage and impairments of mitochondrial functions. Antioxidants have been of
      limited therapeutic success to ameliorate the toxic effects of oxidative stress
      in mitochondria. One reason may be the inability of mitochondria to selectively
      take up antioxidants. In the present study we synthesized mitochondrially
      targeted curcumin with an aim of delivering this polyphenolic compound to
      isolated mitochondria. Our observations show the strong anti-oxidative effects of
      curcumin and mitochondrially targeted curcumin against the lipid peroxidation,
      protein carbonylation and mitochondrial permeability transition induced by tert
      butylhydroperoxide. Both curcumin and mitochondrially targeted curcumin
      significantly enhanced endogenous reduced glutathione level in the mitochondria
      thus preserving mitochondrial defense system against oxidative stress. We
      concluded that curcumin and mitochondrially targeted curcumin protected
      mitochondria against tert-butylhydroperoxide by lowering the oxidative damage,
      increasing the availability of endogenous reduced glutathione and preserving the
      mitochondrial integrity. Importantly, mitochondrially targeted curcumin was found
      most effective in ameliorating oxidative stress and preserving mitochondrial
      integrity than curcumin.

PMID- 24461331
TI  - Acute toxicity of a commercial glyphosate formulation on European sea bass
      juveniles (Dicentrarchus labrax L.): gene expressions of heme oxygenase-1 (ho-1),
      acetylcholinesterase (AChE) and aromatases (cyp19a and cyp19b).
AB  - Acute toxicity of Roundup, a commercial glyphosate--based herbicide, was
      evaluated in a teleost marine fish, the European sea bass, after 96 h of
      exposure. The LC50 96-h value of Roundup was 529 mg/L. Juveniles (Dicentrarchus
      labrax L.) were exposed to a sublethal concentration (35% of the LC50, i.e. 193
      mg/L) of Roundup for 96-h. The study of heme oxygenase-1 (ho-1) gene expression
      was performed in four tissues (liver, gills, brain and gonads) and highlighted
      the disruption of antioxidant defence system. Results showed that ho-1 mRNA
      levels in liver and gills significantly decreased (p<0.001 and p<0.01
      respectively) in fish exposed to 193 mg/L of Roundup, whereas in brain and
      gonads, ho-1 mRNA level was not altered. The analysis of acetylcholinesterase
      expression was used to evaluate the overall neurotoxicity of the herbicide and
      aromatase genes to assess the alteration of the endocrine system. Results showed
      that AChE and cyp19b gene transcriptions significantly increased (p<0.01) in
      brain of sea bass, whereas aromatase gene expression (cyp19a) in gonads was not
      significantly altered. Our results showed complex tissue-specific transcriptional
      responses after 96 h of exposure to a sublethal concentration. All these
      disruptions confirmed the deleterious effects of this glyphosate-based herbicide
      in a marine species.

PMID- 24461332
TI  - Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal
      eosinophilia have similar clinical, endoscopic and histological findings.
AB  - BACKGROUND: Some patients with a phenotypic appearance of eosinophilic
      oesophagitis (EoE) respond histologically to PPI, and are described as having PPI
      responsive oesophageal eosinophilia (PPI-REE). It is unclear if PPI-REE is a GERD
      related phenomenon, a subtype of EoE, or a completely unique entity. AIM: To
      compare demographic, clinical and histological features of EoE and PPI-REE.
      METHODS: Two databases were reviewed from the Walter Reed and Swiss EoE
      databases. Patients were stratified into two groups, EoE and PPI-REE, based on
      recent EoE consensus guidelines. Response to PPI was defined as achieving less
      than 15 eos/hpf and a 50% decrease from baseline following at least a 6-week
      course of treatment. RESULTS: One hundred and three patients were identified (63
      EoE and 40 PPI-REE; mean age 40.2 years, 75% male and 89% Caucasian). The two
      cohorts had similar dysphagia (97% vs. 100%, P = 0.520), food impaction (43% vs.
      35%, P = 0.536), and heartburn (33% vs. 32%, P = 1.000) and a similar duration of
      symptoms (6.0 years vs. 5.8 years, P = 0.850). Endoscopic features were also
      similar between EoE and PPI-REE; rings (68% vs. 68%, P = 1.000), furrows (70% vs.
      70%, P = 1.000), plaques (19% vs. 10%, P = 0.272), strictures (49% vs. 30%, P =
      0.066). EoE and PPI-REE were similar in the number of proximal (39 eos/hpf vs. 38
      eos/hpf, P = 0.919) and distal eosinophils (50 vs. 43 eos/hpf, P = 0.285).
      CONCLUSIONS: EoE and PPI-responsive oesophageal eosinophilia are similar in
      clinical, histological and endoscopic features and therefore are
      indistinguishable without a PPI trial. Further studies are needed to determine
      why a subset of patients with oesophageal eosinophilia respond to PPI.

PMID- 24461333
TI  - Patient and surgeon experience during laser in situ keratomileusis using 2
      femtosecond laser systems.
AB  - PURPOSE: To describe the subjective experience of patients and surgeons during
      laser in situ keratomileusis (LASIK) using the Intralase 60 kHz or the Visumax
      500 kHz femtosecond laser. SETTING: Singapore National Eye Centre, Singapore.
      DESIGN: Prospective randomized clinical study. METHODS: In myopic patients, LASIK
      was performed with the corneal flap created using the 60 kHz laser in 1 eye and
      the 500 kHz laser in the contralateral eye. Postoperatively, patients completed a
      standardized validated questionnaire about their subjective intraoperative
      experiences (eg, light perception, pain, fear). Surgeons reported their
      intraoperative experiences and preferences. RESULTS: Loss of light perception
      occurred in 50.0% of 60 kHz laser cases and 0% of 500 kHz laser cases during
      docking and in 63.0% and 0% of cases, respectively, during laser flap creation (P
      < .0001). The mean pain score with the 60 kHz laser was significantly higher
      during docking (P < .0001) but not during laser flap cutting (P = .006).
      Subconjunctival hemorrhage occurred in 67.4% of eyes with the 60 kHz laser and in
      2.2% of eyes with the 500 kHz laser (P < .0001). The 500 kHz laser was preferred
      by 78.3% of patients, while 21.7% preferred the 60 kHz laser (P < .0001). The
      surgeons preferred the 60 kHz laser in 50.0% of cases and the 500 kHz laser in
      8.7% (P < .0001); 41.3% had no preference. CONCLUSIONS: Patients preferred
      surgery with the 500 kHz laser with no loss of light perception, less pain, less
      fear, and less subconjunctival hemorrhage. Surgeons preferred the 60 kHz laser.

PMID- 24461334
TI  - Chitosan-based biosorbents: modification and application for biosorption of heavy
      metals and radionuclides.
AB  - Heavy metal pollution is a serious environmental problem in the world, especially
      in developing countries. Among different treatment technologies, biosorption
      seems a promising alternative method. Chitosan-based biosorbents are potential
      and effective for heavy metal removal from aqueous solution. The preparation and
      characterization of the natural polymer chitosan, modified chitosan and chitosan
      composites, and their application for the removal or recovery of toxic heavy
      metals, precious metals and radionuclides from wastewater were introduced.
      Chitosan structures and their properties, chitosan modifications (physical
      conditioning and chemical modification), blends and composites as well as the
      metal sorption by chitosan-based biosorbents were briefly presented. The metal
      sorption capacities, influence of intrinsic nature of metal ions, pH and contact
      time, desorbing agents, isotherm and kinetics models, biosorption mechanisms were
      discussed. 

PMID- 24461335
TI  - Under-response correction for EBT3 films in the presence of proton spread out
      Bragg peaks.
AB  - We present a study of the under-response of the new Gafchromic EBT3 films and a
      procedure to accurately perform 2D and 3D proton dosimetry measurements for both
      pristine and spread out Bragg peaks (SOBP) of any energy. These new films differ
      from the previous EBT2 generation by a slightly different active layer
      composition, which we show has not effected appreciably their response. The
      procedure and the beam quality correction factor curve have been benchmarked
      using 29 MeV modulated proton beams. In order to show the correction to apply
      when EBT3 films are used as treatment verification tools in anthropomorphic
      phantoms, two simulation studies involving clinical energies are presented: a
      SOBP for eye treatments and a SOBP to treat 20 cm deep and 5 cm thick tumours. We
      find maximum under-responses of 37%, 30% and 7.7% for the modulated 29 MeV beam,
      eye and deep tumour treatment, respectively, which were attained close to the end
      of the peak tails, due to a higher proportion of very low energy protons. The
      maximum deviations between corrected and uncorrected doses were for the three
      cases, respectively, 20.7%, 8.3% and 2.1% of the average dose across flat region
      of the SOBP. These values were obtained close to the distal edge of the SOBPs,
      where the proportion of low energy protons was not as high as on the tail, but
      there still was a number of protons high enough to deposit a reasonable amount of
      dose in the films. 

PMID- 24461336
TI  - Chemical immobilisation of free-ranging Pampas foxes (Pseudalopex gymnocercus):
      Assessment of ketamine-xylazine and tiletamine-zolazepam combinations.
AB  - Two protocols to immobilise free-ranging Pampas foxes for ear-tagging or radio
      collaring were evaluated. One hundred fifteen foxes were injected with ketamine
      xylazine (K-X) and thirteen with tiletamine-zolazepam (T-Z). The use of both T-Z
      and K-X combinations typically resulted in a smooth induction and recovery. In
      86% of the cases K-X protocol was judged effective (mean+/-SD, K: 10.7+/
      3.3mg/kg, X: 1.0+/-1.0mg/kg) while T-Z protocol was judged effective in 92% of
      the cases (T: 3.6+/-1.05mg/kg, Z: 3.6+/-1.05mg/kg). The primary differences
      between the two drug combinations were that the time necessary for the complete
      recovery was longer with T-Z, and thermic problems were found more frequently
      with K-X. Additionally, our results suggest that thermic stress may be a
      relatively frequent complication for Pampas foxes. This study provides baseline
      data on some physiologic variables in Pampas foxes captured with different
      methods and drugs in field conditions. 

PMID- 24461337
TI  - Stabilization loop of a two axes gimbal system using self-tuning PID type fuzzy
      controller.
AB  - The application of inertial stabilization system is to stabilize the sensor's
      line of sight toward a target by isolating the sensor from the disturbances
      induced by the operating environment. The aim of this paper is to present two
      axes gimbal system. The gimbals torque relationships are derived using Lagrange
      equation considering the base angular motion and dynamic mass unbalance. The
      stabilization loops are constructed with cross coupling unit utilizing proposed
      fuzzy PID type controller. The overall control system is simulated and validated
      using MATLAB. Then, the performance of proposed controller is evaluated comparing
      with conventional PI controller in terms of transient response analysis and
      quantitative study of error analysis. The simulation results obtained in
      different conditions prove the efficiency of the proposed fuzzy controller which
      offers a better response than the classical one, and improves further the
      transient and steady-state performance. 

PMID- 24461338
TI  - Robust master-slave synchronization for general uncertain delayed dynamical model
      based on adaptive control scheme.
AB  - In this paper, the robust exponential synchronization problem for a class of
      uncertain delayed master-slave dynamical system is investigated by using the
      adaptive control method. Different from some existing master-slave models, the
      considered master-slave system includes bounded unmodeled dynamics. In order to
      compensate the effect of unmodeled dynamics and effectively achieve
      synchronization, a novel adaptive controller with simple updated laws is
      proposed. Moreover, the results are given in terms of LMIs, which can be easily
      solved by LMI Toolbox in Matlab. A numerical example is given to illustrate the
      effectiveness of the method. 

PMID- 24461339
TI  - Developing a weekly patient safety and quality meeting in a medium-sized GI
      surgical unit in the United Kingdom.
AB  - BACKGROUND: Morbidity and Mortality (M&M) meetings are advocated as part of good
      surgical practice, but have been criticised as a method of improving patient
      outcomes. Several groups have re-designed the format of M&M meetings to improve
      reporting of complications, near misses and maximise learning points. As a medium
      sized department of 8 GI surgeons in the UK, we wished to explore and discuss the
      complications encountered in our clinical practice in more detail than currently
      available in our monthly M&M/audit meeting, in order to try and improve the
      quality of care we deliver to our patients. This article describes the
      practicalities of introducing a weekly meeting and reports on the initial data
      generated from the patients discussed. METHODS: Four groups of general surgical
      patients (both elective and acute) are discussed in depth at the weekly meeting-
      a) patients whose length of in-patient stay is greater than 7 days (as a
      surrogate marker of a complicated surgical episode), b) unplanned patient
      readmissions to our hospital (under any specialty) within 30 days of a previous
      discharge from the GI surgical service, c) all GI surgical inpatient deaths and
      d) returns to theatre within the same admission (either planned or unplanned).
      RESULTS: The initial data generated from the meeting first six months of the
      meeting are presented e.g.- 302 length of stay greater than 7 days patient
      episodes (attributable to complications in 26%, normal variant of disease in 59%
      and social reasons delaying discharge in 15%). CONCLUSIONS: We feel that these
      weekly meetings can be helpful in addressing both patient safety and quality
      issues in more depth than the traditional M&M format, as well as being a valuable
      training resource for both surgical trainees and consultants alike.

PMID- 24461341
TI  - [Obstetrical complications of genital mutilation in Malian rural environment].
AB  - OBJECTIVE: To describe maternal and fetal complications during delivery of
      mutilated women. MATERIALS AND METHODS: It was a case study, witnesses with
      matching going from February 1st, 2008 till January 31st, 2009 which took place
      in Mopti's region. We compared maternal and fetal complications of mutilated and
      non-mutilated women. Using statistical tests were Chi(2) (P<0.05), Odd-Ratio (OR)
      and its 95% confident interval (CI95%). RESULTS: We recorded 410 deliveries among
      which 280 mutilated women (68%). One hundred and forty excised women were
      included. There is a significant difference between duration of eviction>30 mm
      (RC=8.27 [4.66-14.76], P<0.001); simple perennials lacerations (RC=14.54 [4.79
      49.56], P<0.001) and full perennials lacerations (RC=8.90 [1.91-57.23], P<0.001)
      in the two groups. The scores of morbid Apgar (RC=9.70 [4.35-22,29], P<0.001)
      were more important in groups of cases. Moreover, we recorded 3 neonatal deaths
      and 4 complicated perennials lacerations in the group of cases only. CONCLUSION:
      Maternal and fetal complications are significantly more important for the excised
      woman's than for the not excised women.

PMID- 24461340
TI  - [Klippel-Trenaunay syndrome and pregnancy: difficult choice of delivery from a
      case and a review of the literature].
AB  - Klippel-Trenaunay syndrome (SKT) is a rare disease characterized by cutaneous
      haemangiomas, capillary malformations venous (venous varicosities), bone and soft
      tissue hypertrophy affecting one or more limbs. It is often associated with
      hemorrhagic and thrombotic complications, especially during pregnancy.
      Vulvovaginal anomalies at risk of bleeding may occur in late trimester of
      pregnancy, affecting delivery. The terms of delivery depends on the severity of
      vascular malformations and the experience of the obstetrician. We report the case
      of a woman in labor at 38 weeks gestation with a SKT with involvement of the left
      leg up to the corresponding large lip. She presented after vaginal delivery a
      severe post-partum hemorrhage (2000mL) secondary to vaginal lacerations requiring
      sutures and supplemented by arterial embolization. A multidisciplinary approach
      is required at delivery. 

PMID- 24461342
TI  - Hypoxemia in sickle cell disease: significance and management.
AB  - Hypoxemia is common in SCD and likely exacerbates SCD vasculopathy. Pulse
      oximeter correlation with arterial oxygen tension in patients with SCD may at
      times be poor and arterial blood gas confirmation is required in hypoxic
      patients. Supplemental oxygen should be administered for the correction of
      hypoxemia, which if untreated creates a risk of multi-organ failure. Transfusion
      and hydroxyurea can improve oxygen delivery to tissues and organs. The role of
      supplemental oxygen therapy in preventing or reversing SCD vasculopathy is
      controversial. Nitric oxide therapy for VOC pain has not fulfilled promise to
      date. On the other hand, lung distension (CPAP, incentive spirometry, PEP
      therapy) are promising treatments requiring further study. 

PMID- 24461343
TI  - Demonstrations of subconscious processing with the binary exclusion task.
AB  - The binary exclusion task involves "subtle priming effects" and a measure of
      awareness that is reliable, relevant, immediate, and sensitive. This task, which
      meets the criteria outlined in the target article, has been used to demonstrate
      subconscious processing. 

PMID- 24461344
TI  - Cognitive subtypes of mathematics learning difficulties in primary education.
AB  - It has been asserted that children with mathematics learning difficulties (MLD)
      constitute a heterogeneous group. To date, most researchers have investigated
      differences between predefined MLD subtypes. Specifically MLD children are
      frequently categorized a priori into groups based on the presence or absence of
      an additional disorder, such as a reading disorder, to examine cognitive
      differences between MLD subtypes. In the current study 226 third to six grade
      children (M age=131 months) with MLD completed a selection of number specific and
      general cognitive measures. The data driven approach was used to identify the
      extent to which performance of the MLD children on these measures could be
      clustered into distinct groups. In particular, after conducting a factor
      analysis, a 200 times repeated K-means clustering approach was used to classify
      the children's performance. Results revealed six distinguishable clusters of MLD
      children, specifically (a) a weak mental number line group, (b) weak ANS group,
      (c) spatial difficulties group, (d) access deficit group, (e) no numerical
      cognitive deficit group and (f) a garden-variety group. These findings imply that
      different cognitive subtypes of MLD exist and that these can be derived from data
      driven approaches to classification. These findings strengthen the notion that
      MLD is a heterogeneous disorder, which has implications for the way in which
      intervention may be tailored for individuals within the different subtypes. 

PMID- 24461345
TI  - [Morbidity and mortality cardiovascular risk in dependence of type 2 diabetes
      duration].
AB  - INTRODUCTION: This study was aimed to assess the prognostic importance of
      diabetes duration to predict cardiovascular risk in type 2 diabetic patients.
      METHODS: Prospective cohort study with inclusion of type 2 diabetic patients.
      Follow-up lasted until the appearance of a cardiovascular event, until death or
      until 2012. Patients were classified into 5 groups in accordance to diabetes
      duration and baseline cardiovascular disease (CVD): group 1: <= 5 years without
      CVD; group 2: 6-10 years without CVD; group 3: 11-15 years without CVD; group 4:
      >15 years without CVD; group 5: baseline CVD independently of diabetes duration.
      CVD rates were expressed per 1000 patients-year and compared by Kaplan-Meier
      analysis and Log Rank Test. The predictive power of diabetes duration was
      evaluated by Cox regression. RESULTS: 457 patients, aged 64.9 (DE 9.3) years
      (38.9% males), were included. Diabetes duration was 10.5 (DE 7.6) years. 125
      cardiovascular events occurred during 12.3 years follow-up. Cardiovascular event
      rates were progressively increased from groups 1 to 5 (group 1: 14.1; group 2:
      18.3; group 3: 19.6; group 4: 32.9; group 5: 53.5; p<0.0001, linear tendency).
      Diabetes duration superior to 15 years significantly increased cardiovascular
      risk of the patients (HR=1.97; 95%CI: 1.23-3.15; P=.004). CONCLUSIONS: It could
      be useful to consider diabetes duration in order to stratify cardiovascular risk
      of type 2 diabetic patients.

PMID- 24461347
TI  - [Kutuzov's phthisis bulbi].

PMID- 24461346
TI  - Prevalence of plasma lipid abnormalities and its association with glucose
      metabolism in Spain: the di@bet.es study.
AB  - INTRODUCTION: Dyslipidemia is a significant contributor to the elevated CVD risk
      observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia
      and its association with glucose metabolism status in a representative sample of
      the adult population in Spain and the percentage of subjects at guideline
      recommended LDL-C goals. MATERIAL AND METHODS: The di@bet.es study is a national,
      cross-sectional population-based survey of 5728 adults. RESULTS: A total of 4776
      subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only
      13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities
      were found in 56.8% of Spanish adults: 23.3% with high LDL-C, 21.5% high TG,
      35.8% high non-HDL-C, and 17.2% low HDL-C. Most normal subjects showed an LDL-C
      <= 3.36 mmol/l. Pre-diabetics presented similar proportion when considering a
      goal of 3.36 mmol/l, but only 35% of them reached an LDL-C goal <= 2.6 mmol/l.
      Finally, 45.3% of diabetics had an LDL-C <= 2.6 mmol/l, and only 11.3% achieved
      an LDL-C <= 1.8 mmol/l. CONCLUSIONS: Our study demonstrates a high prevalence of
      dyslipidemia in the adult Spanish population, and a low use of lipid-lowering
      drugs. Moreover, the number of subjects achieving their corresponding LDL-C goal
      is small, particularly in subjects at high cardiovascular risk, such as
      diabetics.

PMID- 24461348
TI  - [Visual snow. From a symptom to a syndrome?].

PMID- 24461349
TI  - The problem of consciousness in habitual decision making.
AB  - Newell & Shanks (N&S) carry out an extremely sharp and static distinction between
      conscious and unconscious decisions, ignoring a process that dynamically
      transfers decisions and actions between the conscious and unconscious domains of
      the mind: habitual decision making. We propose a new categorisation and discuss
      the main characteristics of this process from a philosophical and neuroscientific
      perspective. 

PMID- 24461350
TI  - [Surgical treatment of locally aggressive and malignant tumors of the proximal
      third of the fibula. Oncology results and functional evaluation].
AB  - INTRODUCTION: Proximal fibula malignant and locally aggressive benign bone tumors
      are uncommon and usually treat by surgery. Bloc resection of the knee can
      compromise knee stability due to of the resection of the posterolateral ligament
      complex. MATERIAL AND METHODS: We analyzed 28 consecutive patients treated for a
      proximal fibula bone tumor between 1980 and 2006 (osteosarcoma: 9, giant cell
      tumor: 9, Ewing sarcoma: 8 and chondrosarcoma: 2). Sixty-one percent were male
      and the median age was 21 years (range: 8-60). The mean follow-up was 86 months.
      The posterolateral complex was reinserted at tibial metaphyseal level. Patients
      were evaluated functionally using the Musculoskeletal Tumor Society scale (MSTS).
      RESULTS: Overall survival rate was 89%, local recurrence rate was 11%, and
      secondary amputation rate was 6% at 7 years of median follow-up. The average MSTS
      score was 93%. Five patients had neurological complications. No patient
      experienced subjective instability or vascular insufficiency. CONCLUSIONS: Bloc
      resection of the proximal fibula for the treatment of aggressive or malignant
      primary bone tumors allowed us to obtain local tumor control, and overall
      survival rate for sarcomas of 89% at 7 years. The posterolateral ligament complex
      tibial reinsertion provided functional knee stability without major functional
      consequences in the medium term.

PMID- 24461352
TI  - Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: development of a
      potent and CNS penetrant [3.1.0]-based lead.
AB  - This Letter describes the development and SAR of a novel series of GlyT1
      inhibitors derived from a scaffold hopping approach that provided a robust
      intellectual property position, in lieu of a traditional, expensive HTS campaign.
      Members within this new [3.1.0]-based series displayed excellent GlyT1 potency,
      selectivity, free fraction, CNS penetration and efficacy in a preclinical model
      of schizophrenia (prepulse inhibition). 

PMID- 24461351
TI  - Predicting the molecular interactions of CRIP1a-cannabinoid 1 receptor with
      integrated molecular modeling approaches.
AB  - Cannabinoid receptors are a family of G-protein coupled receptors that are
      involved in a wide variety of physiological processes and diseases. One of the
      key regulators that are unique to cannabinoid receptors is the cannabinoid
      receptor interacting proteins (CRIPs). Among them CRIP1a was found to decrease
      the constitutive activity of the cannabinoid type-1 receptor (CB1R). The aim of
      this study is to gain an understanding of the interaction between CRIP1a and CB1R
      through using different computational techniques. The generated model
      demonstrated several key putative interactions between CRIP1a and CB1R, including
      the critical involvement of Lys130 in CRIP1a. 

PMID- 24461353
TI  - Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as
      anti-prostate cancer drugs.
AB  - A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized
      and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a
      novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4
      dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using
      a recombinant PCA-1/ALKBH3, 1-(1H-5-methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H
      pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both
      in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral
      administration. As expected, continuously administering 35 significantly
      suppressed the growth of DU145 cells, which are human hormone-independent
      prostate cancer cells, in a mouse xenograft model without untoward effects. 

PMID- 24461354
TI  - A novel method to replicate the kinematics of the carpus using a six degree-of
      freedom robot.
AB  - Understanding the kinematics of the carpus is essential to the understanding and
      treatment of wrist pathologies. However, many of the previous techniques
      presented are limited by non-functional motion or the interpolation of points
      from static images at different postures. We present a method that has the
      capability of replicating the kinematics of the wrist during activities of daily
      living using a unique mechanical testing system. To quantify the kinematics of
      the carpal bones, we used bone pin-mounted markers and optical motion capture
      methods. In this paper, we present a hammering motion as an example of an
      activity of daily living. However, the method can be applied to a wide variety of
      movements. Our method showed good accuracy (1.0-2.6 degrees ) of in vivo movement
      reproduction in our ex vivo model. Most carpal motion during wrist flexion
      extension occurs at the radiocarpal level while in ulnar deviation the motion is
      more equally shared between radiocarpal and midcarpal joints, and in radial
      deviation the motion happens mainly at the midcarpal joint. For all rotations,
      there was more rotation of the midcarpal row relative to the lunate than relative
      to the scaphoid or triquetrum. For the functional motion studied (hammering),
      there was more midcarpal motion in wrist extension compared to pure wrist
      extension while radioulnar deviation patterns were similar to those observed in
      pure wrist radioulnar deviation. Finally, it was found that for the amplitudes
      studied the amount of carpal rotations was proportional to global wrist
      rotations. 

PMID- 24461355
TI  - Factorial validation of the Attitudes toward Women Scale for Adolescents (AWSA)
      in assessing sexual behaviour patterns in Bolivian and Ecuadorian adolescents.
AB  - BACKGROUND: Adolescents' health is greatly influenced by social determinants,
      including gender norms. Although research has shown that there is an association
      between gender attitudes and adolescents' sexual behaviour, few studies have
      assessed this relationship carefully. The Attitudes toward Women Scale for
      Adolescents (AWSA) is widely used to assess gender attitudes among adolescents;
      however, to our knowledge it has not been applied in Latin America. OBJECTIVE: To
      apply AWSA in Latin America for the first time, to perform a factorial validation
      of this scale and to assess the relationship of gender attitudes and sexual
      behaviour in Bolivian and Ecuadorian adolescents. DESIGN: This cross-sectional
      study was carried out in 2011 among 14-18 year olds in 20 high schools in
      Cochabamba (Bolivia) and six in Cuenca (Ecuador) as a part of a larger project.
      Schools were purposively selected. A Spanish version of the 12-item AWSA was
      employed for this study. The assessed aspects of adolescent sexual behaviour
      were: reported sexual intercourse, reported positive experience during last
      sexual intercourse and reported current use of contraception. The psychometric
      properties of AWSA were investigated, and both explanatory and confirmatory
      factorial analyses were performed. RESULTS: The number of questionnaires included
      in the analysis was 3,518 in Bolivia and 2,401 in Ecuador. A factorial analysis
      of AWSA resulted in three factors: power dimension (PD), equality dimension (ED)
      and behavioural dimension (BD). ED showed the highest correlates with adolescent
      sexual behaviour. Higher scores of this dimension were associated with a more
      positive experience of sexual relationships, a higher current use of modern
      contraception and greater sexual activity among girls. CONCLUSIONS: This study
      revealed a three-factorial structure of AWSA and demonstrated that by employing
      factors, the sensitivity of AWSA increases as compared to using the scale as a
      whole to assess sexual behaviour. This could have important implications for
      future research on gender and the sexual experiences of adolescents.

PMID- 24461356
TI  - Assessing the technical efficiency of health posts in rural Guatemala: a data
      envelopment analysis.
AB  - INTRODUCTION: Strengthening health service delivery to the rural poor is an
      important means of redressing inequities. Meso-level managers can help enhance
      efficiency in the utilization of existing resources through the application of
      practical tools to analyze routinely collected data reflecting inputs and
      outputs. This study aimed to assess the efficiency and change in productivity of
      health posts over two years in a rural department of Guatemala. METHODS: Data
      envelopment analysis was used to measure health posts' technical efficiency and
      productivity change for 2008 and 2009. Input/output data were collected from the
      regional health office of Alta Verapaz for 34 health posts from the 19 districts
      comprising the health region. RESULTS: Technical efficiency varied widely across
      health posts, with mean scores of 0.78 (SD=0.24) and 0.75 (SD=0.21) in 2008 and
      2009, respectively. Overall, productivity increased by 4%, though 47% of health
      posts experienced a decline in productivity. Results were combined on a bivariate
      plot to identify health posts at the high and low extremes of efficiency, which
      should be followed up to determine how and why their production processes are
      operating differently. CONCLUSIONS: Assessing efficiency using the data that are
      available at the meso-level can serve as a first step in strengthening
      performance. Further work is required to support managers in the routine
      application of efficiency analysis and putting the results to use in guiding
      efforts to improve service delivery and increase utilization.

PMID- 24461357
TI  - Cervical spine stenosis after uneventful coronary artery bypass surgery.

PMID- 24461358
TI  - An unusual cause of severe mitral regurgitation in a patient with aortic valve
      endocarditis.

PMID- 24461359
TI  - Perioperative management of patients with DiGeorge syndrome undergoing cardiac
      surgery.
AB  - OBJECTIVE: DiGeorge syndrome is a genetic disorder with multisystem involvement
      resulting in craniofacial and cardiac anomalies and parathyroid and immune system
      dysfunction. This study describes perioperative management of a large cohort of
      patients with DiGeorge syndrome undergoing cardiac surgery. DESIGN: Retrospective
      cohort study. SETTING: Major academic tertiary institution. PARTICIPANTS: The
      medical records of patients diagnosed with DiGeorge syndrome and undergoing
      cardiac surgery at this institution, from January 1, 1976, to July 31, 2012, were
      reviewed for phenotypic characteristics and intraoperative and postoperative
      complications, with specific attention to hemodynamic instability, perioperative
      perturbations of plasma calcium homeostasis, and airway difficulty.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-two patients underwent
      136 cardiac surgical procedures; 47 patients (76%) had multiple operations.
      Sternotomies for reoperations often were complex (8 complicated by vascular
      injury or difficulty achieving hemostasis and 5 requiring bypass before
      sternotomy). Two patients had persistent hypocalcemia intraoperatively, requiring
      infusion of calcium chloride, and hypocalcemia developed postoperatively in 8
      patients. Prolonged mechanical ventilation (>24 hours) was required after 48
      procedures (35%), and 25 (18%) required prolonged inotropic support (>72 hours).
      Infectious complications occurred after 31 procedures (23%). There was no in
      hospital or 30-day mortality. CONCLUSIONS: Patients with DiGeorge syndrome often
      have complex cardiac anomalies that require surgical repair. The postoperative
      course is notable for the frequent need for prolonged respiratory and hemodynamic
      support. Patients can develop hypocalcemia and may require calcium
      supplementation. Immunodeficiencies may be associated with the increased rate of
      postoperative infections and may dictate the need for specific transfusion
      management practices.

PMID- 24461360
TI  - Simultaneous use of two defibrillators for the conversion of refractory
      ventricular fibrillation.

PMID- 24461361
TI  - Anesthesia and LEOPARD syndrome: a review of forty-nine anesthetic exposures.
AB  - OBJECTIVES: LEOPARD syndrome is a rare congenital disease that can manifest with
      cardiac anomalies, multiple lentigines, ocular hypertelorism, growth retardation,
      and deafness. The purpose of this case series was to review the most prominent
      comorbidities associated with LEOPARD syndrome, and describe perioperative
      outcomes in a series of patients undergoing anesthesia. DESIGN: Retrospective
      case series review SETTING: Tertiary care institution PARTICIPANTS: Patients
      diagnosed with LEOPARD syndrome who underwent surgical procedures requiring
      anesthesia at this institution. INTERVENTION: The medical and anesthesia records
      of patients with LEOPARD syndrome were reviewed. Demographic information,
      clinical features of LEOPARD syndrome, comorbidities, intraoperative and
      postoperative events and complications were recorded. A systematic literature
      review also was conducted. MEASUREMENTS AND MAIN RESULTS: Nine patients with
      LEOPARD syndrome underwent 49 procedures under general anesthesia (n = 40) or
      monitored anesthesia care (n = 9). The majority of operations were related to
      correction of cardiac anomalies (n = 20). The most common cardiac malformations
      were ventricular septal hypertrophy and pulmonary (or subpulmonary) stenosis, and
      major perioperative complications were related to severe arrhythmias and/or
      cardiac decompensation. CONCLUSIONS: Dominant pathology associated with
      perioperative complications in patients with LEOPARD syndrome is related to
      cardiac disease. A large proportion of patients with this condition have
      ventricular septal hypertrophy, which tends to progress with age; therefore,
      these patients undergoing anesthesia should have recent cardiologist evaluation.

PMID- 24461362
TI  - Retrosternal hematoma after aortic valve replacement: ultrasound view.

PMID- 24461363
TI  - CASE 12--2014. Inferior vena cava compression by retroperitoneal hematoma during
      cardiopulmonary bypass.

PMID- 24461364
TI  - Heparinase thromboelastography compared with activated coagulation time for
      protamine titration after cardiopulmonary bypass.
AB  - OBJECTIVE: The present study is a comparison of two point-of-care (POC) tests as
      endpoints of protamine titration after CPB. The authors hypothesized that using
      the heparinase-kaolin thromboelastography (TEG-HK) R-time difference would more
      readily identify residual heparin necessitating additional protamine than when
      using activated coagulation time (ACT). The primary endpoint was the between
      group difference in protamine dose. Whether this approach would lessen
      postoperative bleeding and sequelae also was investigated. DESIGN: Single center,
      blinded, prospective, randomized study. SETTING: University teaching hospital.
      PARTICIPANTS: Eighty-two adult patients for on-pump coronary artery bypass and/or
      valve surgery. INTERVENTIONS: Patients were randomized. In the ACT group,
      protamine was titrated until ACT did not exceed baseline by more than 10%. In the
      TEG group, a TEG-HK R-time difference less than 20% was targeted. Protamine was
      repeated to achieve the endpoints. Clinicians in the ACT group were blinded to
      TEG data and vice versa. MEASUREMENTS AND MAIN RESULTS: There was no between
      group difference in total protamine dose (3.9 +/- 0.6 and 4.2 +/- 0.7; 95% CI of
      the difference between means: -0.544 to 0.008 mg/kg; p = 0.057) or
      protamine:heparin ratios (1.3:1 and 1.4:1; 95% CI of the difference between
      means: -0.05 to 0.03 mg/mg; p = 0.653). In the ACT group, 17% of patients
      required a second protamine dose, and in the TEG group, 24% of patients required
      a second protamine dose. No between-group differences in the postoperative
      transfusion requirements or intensive care unit length of stay were demonstrated.
      CONCLUSION: No difference was identified in protamine dosing using either ACT or
      TEG-HK R-time difference as endpoints. Heparinase TEG may be useful for
      monitoring heparin reversal.

PMID- 24461365
TI  - Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in
      murine erythroleukemia cells.
AB  - The nitric oxide (NO) prodrug JS-K, a promising anti-cancer agent, consists of a
      diazeniumdiolate group necessary for the release of NO as well as an arylating
      ring. In this study, we research the mechanism by which JS-K kills a murine
      erythroleukemia cell line and determine the roles of NO and arylation in the
      process. Our studies indicate that JS-K inhibits the PI 3-kinase/Akt and MAP
      kinase pathways. This correlates with the activation of the tumor suppressor
      FoxO3a and increased expression of various caspases, leading to apoptosis. The
      arylating capability of JS-K appears to be sufficient for inducing these
      biological effects. Overall, these data suggest that JS-K kills tumor cells by
      arylating and inactivating signaling molecules that block the activation of a
      tumor suppressor. 

PMID- 24461368
TI  - Self-insight research as (double) model recovery.
AB  - Self-insight assessment compares outcomes from two model-recovery exercises: a
      statistical exercise to infer a judge's (implicit) policy and an elicitation
      exercise whereby the judge describes his or her (explicit) policy. When these
      policies are mismatched, limited self-insight is not necessarily implied:
      Shortcomings in either exercise could be implicated, whereby Newell & Shanks'
      (N&S's) relevance or sensitivity criteria for assessing awareness may not be met.
      Appropriate self-insight assessment requires that both exercises allow the
      original processes to be captured. 

PMID- 24461366
TI  - Alterations of Ca2+-responsive proteins within cholinergic neurons in aging and
      Alzheimer's disease.
AB  - The molecular basis of selective neuronal vulnerability in Alzheimer's disease
      (AD) remains poorly understood. Using basal forebrain cholinergic neurons (BFCNs)
      as a model and immunohistochemistry, we have demonstrated significant age-related
      loss of the calcium-binding protein calbindin-D(28K) (CB) from BFCN, which was
      associated with tangle formation and degeneration in AD. Here, we determined
      alterations in RNA and protein for CB and the Ca(2+)-responsive proteins
      Ca(2+)/calmodulin-dependent protein kinase I (CaMKI), growth-associated protein
      43 (GAP43), and calpain in the BF. We observed progressive downregulation of CB
      and CaMKI RNA in laser-captured BFCN in the normal-aged-AD continuum. We also
      detected progressive loss of CB, CaMKIdelta, and GAP43 proteins in BF homogenates
      in aging and AD. Activated MU-calpain, a calcium-sensitive protease that degrades
      CaMKI and GAP43, was significantly increased in the normal aged BF and was 10
      times higher in AD BF. Overactivation of MU-calpain was confirmed using
      proteolytic fragments of its substrate spectrin. Substantial age- and AD-related
      alterations in Ca(2+)-sensing proteins most likely contribute to selective
      vulnerability of BFCN to degeneration in AD.

PMID- 24461369
TI  - The OECD expert meeting on ecotoxicology and environmental fate--towards the
      development of improved OECD guidelines for the testing of nanomaterials.
AB  - On behalf of the OECD Working Party on Manufactured Nanomaterials (WPMN) an
      expert meeting on ecotoxicology and environmental fate of nanomaterials (NMs)
      took place in January 2013 in Berlin. At this meeting experts from science,
      industry and regulatory bodies discussed the applicability of OECD test
      guidelines (TGs) for chemicals to nanomaterials. The objective was to discuss the
      current state of the relevant science and provide recommendations to the OECD
      WPMN on (1) the need for updating current OECD TGs and the need for developing
      new ones specific to nanomaterials; and (2) guidance needed for the appropriate
      and valid testing of environmental fate and ecotoxicity endpoints for NMs.
      Experts at the workshop agreed that the majority of the OECD TG for chemicals
      were generally applicable for the testing of NM, with the exception of TG 105
      (water solubility) and 106 (adsorption-desorption). Additionally, the workshop
      also highlighted considerations when conducting OECD chemical TG on nanomaterials
      (e.g., sample preparation, dispersion, analysis, dosimetry and characterisation).
      These considerations will lead to the future development of proposals for new TG
      and guidance documents (GDs) to ensure that OECD TG give meaningful, repeatable,
      and accurate results when used for nanomaterials. This report provides a short
      overview of topics discussed during the meeting and the main outcomes. A more
      detailed report of the workshop will become available through the OECD, however,
      due to the urgency of having OECD TG relevant for nanomaterials, this brief
      report is being shared with the scientific community through this communication. 

PMID- 24461370
TI  - Web- vs. telehealth-based delivery of cognitive behavioral therapy for insomnia:
      a randomized controlled trial.
AB  - OBJECTIVES: The purpose of our study was to evaluate and compare two methods of
      service delivery (web-based and telehealth-based) for chronic insomnia with
      regard to patient preference, clinical effectiveness, and patient satisfaction.
      METHODS: Our study was a randomized controlled trial with manualized telehealth-
      and web-based delivery conditions (nonblinded). The sample comprised 73 adults
      with chronic insomnia. Participants received web-based delivery from their homes
      or telehealth-based delivery from a nearby clinic. Both interventions consisted
      of identical psychoeducation, sleep hygiene and stimulus control instruction,
      sleep restriction treatment, relaxation training, cognitive therapy, mindfulness
      meditation, and medication-tapering assistance. RESULTS: Using a linear mixed
      model analysis, results showed that both delivery methods produced equivalent
      changes in insomnia severity, with large effect sizes. Attendance patterns
      favored telehealth, whereas homework adherence and preference data favored web
      based delivery. CONCLUSIONS: Web- and telehealth-based delivery are both helpful
      in treating chronic insomnia in rural-dwelling adults.

PMID- 24461371
TI  - Response to, "The sleep lost".

PMID- 24461367
TI  - Corneal nerves in health and disease.
AB  - Corneal nerves are responsible for the sensations of touch, pain, and temperature
      and play an important role in the blink reflex, wound healing, and tear
      production and secretion. Corneal nerve dysfunction is a frequent feature of
      diseases that cause opacities and result in corneal blindness. Corneal opacities
      rank as the second most frequent cause of blindness. Technological advances in in
      vivo corneal nerve imaging, such as optical coherence tomography and confocal
      scanning, have generated new knowledge regarding the phenomenological events that
      occur during reinnervation of the cornea following disease, injury, or surgery.
      The recent availability of transgenic neurofluorescent murine models has
      stimulated the search for molecular modulators of corneal nerve regeneration. New
      evidence suggests that neuroregenerative and inflammatory pathways in the cornea
      are intertwined. Evidence-based treatment of neurotrophic corneal diseases
      includes using neuroregenerative (blood component-based and neurotrophic
      factors), neuroprotective, and ensconcing (bandage contact lens and amniotic
      membrane) strategies and avoiding anti-inflammatory therapies, such as
      cyclosporine and corticosteroids.

PMID- 24461372
TI  - Reviewing systematic reviews and analyzing meta-analyses.

PMID- 24461374
TI  - Towards a methodology of language evolution modelling: Comment on "Modelling
      language evolution: Examples and predictions" by Gong, Shuai and Zhang.

PMID- 24461373
TI  - Action semantics: A unifying conceptual framework for the selective use of
      multimodal and modality-specific object knowledge.
AB  - Our capacity to use tools and objects is often considered one of the hallmarks of
      the human species. Many objects greatly extend our bodily capabilities to act in
      the physical world, such as when using a hammer or a saw. In addition, humans
      have the remarkable capability to use objects in a flexible fashion and to
      combine multiple objects in complex actions. We prepare coffee, cook dinner and
      drive our car. In this review we propose that humans have developed declarative
      and procedural knowledge, i.e. action semantics that enables us to use objects in
      a meaningful way. A state-of-the-art review of research on object use is
      provided, involving behavioral, developmental, neuropsychological and
      neuroimaging studies. We show that research in each of these domains is
      characterized by similar discussions regarding (1) the role of object
      affordances, (2) the relation between goals and means in object use and (3) the
      functional and neural organization of action semantics. We propose a novel
      conceptual framework of action semantics to address these issues and to integrate
      the previous findings. We argue that action semantics entails both multimodal
      object representations and modality-specific sub-systems, involving manipulation
      knowledge, functional knowledge and representations of the sensory and
      proprioceptive consequences of object use. Furthermore, we argue that action
      semantics are hierarchically organized and selectively activated and used
      depending on the action intention of the actor and the current task context. Our
      framework presents an integrative account of multiple findings and perspectives
      on object use that may guide future studies in this interdisciplinary domain.

PMID- 24461375
TI  - Is a single 'hub', with lots of spokes, an accurate description of the neural
      architecture of action semantics?: Comment on "Action semantics: A unifying
      conceptual framework for the selective use of multimodal and modality-specific
      object knowledge" by van Elk, van Schie and Bekkering.

PMID- 24461376
TI  - Induction motors airgap-eccentricity detection through the discrete wavelet
      transform of the apparent power signal under non-stationary operating conditions.
AB  - Fast Fourier transform (FFT) analysis has been successfully used for fault
      diagnosis in induction machines. However, this method does not always provide
      good results for the cases of load torque, speed and voltages variation, leading
      to a variation of the motor-slip and the consequent FFT problems that appear due
      to the non-stationary nature of the involved signals. In this paper, the discrete
      wavelet transform (DWT) of the apparent-power signal for the airgap-eccentricity
      fault detection in three-phase induction motors is presented in order to overcome
      the above FFT problems. The proposed method is based on the decomposition of the
      apparent-power signal from which wavelet approximation and detail coefficients
      are extracted. The energy evaluation of a known bandwidth permits to define a
      fault severity factor (FSF). Simulation as well as experimental results are
      provided to illustrate the effectiveness and accuracy of the proposed method
      presented even for the case of load torque variations. 

PMID- 24461377
TI  - Effects of chronic desipramine pretreatment on open field-induced suppression of
      blood natural killer cell activity and cytokine response depend on the rat's
      behavioral characteristics.
AB  - Effects of 14 consecutive day exposure to desipramine (10mg/kg i.p.), by itself
      or following chronic open field (OF) exposure, on subsequent neuroimmunological
      effects of acute (30 min) OF stress and the involvement of individual differences
      in response to novelty or social position in the anti-depressive responsiveness
      were investigated. Chronic desipramine pretreatment did not protect against OF
      stress-induced suppression of blood anti-tumor natural killer cell activity but
      increased plasma interleukin-10 and decreased interferon-gamma and corticosterone
      concentration. These effects were particularly dangerous for the animals with
      increased responsivity to stress (desipramine alone) or with low behavioral
      activity (desipramine after chronic stress).

PMID- 24461378
TI  - [Intensity-modulated radiotherapy in cervical cancer: towards a new standard?].
AB  - Intensity modulated radiation therapy has demonstrated its ability to prevent
      xerostomia in the treatment of head and neck cancers, as well as post-radiation
      related proctitis in prostate cancer. In the management of cervical carcinomas,
      many published dosimetric studies have shown its ability to limit the irradiation
      of organs at risk. However, clinical data remain limited to comparisons of
      cohorts, mostly retrospective, but promising. This review aims to update the
      current state of knowledge. 

PMID- 24461379
TI  - Heart rate recovery after the 10-m incremental shuttle walking test in older
      adults with intellectual disabilities.
AB  - Heart rate recovery (HRR) after exercise is an independent predictor for
      cardiovascular and all-cause mortality. To investigate the usefulness of HRR in
      cardiorespiratory exercise testing in older adults with intellectual disabilities
      (ID), the aims of this study were (a) to assess HRR in older adults with ID after
      the 10-m incremental shuttle walking test (ISWT) and (b) its association with
      personal characteristics (gender, age, distance walked on the ISWT, level of ID,
      genetic syndrome causing ID, autism, behavioral problems, and peak heart rate
      (HRpeak)). HRR was assessed after the 10-m incremental shuttle walking test in
      300 older adults (>50 years) with borderline to profound ID. HRR was defined as
      the change from HRpeak during the ISWT to heart rate measured after 1, 2, 3, 4,
      and 5 min of passive recovery. The largest decrease in heart rate was in the
      first minute of recovery leveling off toward the fifth minute of recovery. An
      abnormal HHR (<=12 bpm) was seen in 36.1% of the participants with Down syndrome
      (DS) and in 30.7% of the participants with ID by other causes. After the fifth
      minute the heart rates of 69.4% of the participants with DS and of 61.4% of the
      participants with ID by other causes returned to resting levels. HRpeak and
      distance walked on the ISWT were positively related to all HRR measures. More
      severe ID was negatively related and having DS positively related to HRR after 3
      5 min of recovery. The other characteristics were not significantly associated to
      HRR. HRR is a potentially useful outcome measure in cardiorespiratory fitness
      testing of older adults with ID with a direct, objective, and non-invasive
      measurement. Further research is needed to identify the relation between HRR and
      adverse health outcomes in this population.

PMID- 24461380
TI  - The diagnosis and classification of polymyositis.
AB  - Polymyositis is classified as a separate entity among idiopathic inflammatory
      myopathies but it is considered as the least common since it is an exclusion
      diagnosis. This myopathy usually presents with subacute-chronic symmetric
      proximal limb weakness, although some extramuscular manifestations are common.
      Creatine kinase values may be increased up to 50-fold in active disease. Muscle
      biopsy is characterized by endomysial inflammatory infiltrate consisting
      predominantly of CD8+ T cells that invade healthy muscle fibres expressing the
      MHC-I antigen. Although serum autoantibodies, EMG and imaging techniques can help
      in diagnosis, muscle histopathology is a pivotal value. The clinical picture
      together with the pathological findings confers the also called PM pattern. A
      broad differential diagnosis is needed before concluding a diagnosis of pure PM.
      Sporadic inclusion-body myositis, toxic, endocrine and metabolic myopathies as
      well as muscular dystrophies are the major categories to be ruled out. Finally, a
      diagnostic algorithm for suspected cases of PM is also proposed. 

PMID- 24461381
TI  - Diagnostic and classification criteria of Takayasu arteritis.
AB  - Takayasu arteritis (TA) is a chronic large vessel vasculitis that affects aorta,
      its main branches and pulmonary arteries. The inflammatory process results in
      stenosis, occlusion, dilation or aneurysm formation in the arterial wall. TA has
      been described in different parts of the world and affects predominantly young
      individuals (<50 years of age). Patients with TA may present constitutional
      symptoms, vascular pain (e.g. carotidynia) and typical features such as limb
      claudication, decreased or absent peripheral pulses, vascular bruits,
      hypertension, and reduction or discrepancies in blood pressure between arms. A
      proper diagnosis of TA is an important issue since delays may result in
      significant morbidity. The definition of TA was included in the 1994 and 2012
      Chapel Hill Consensus Conference and TA was categorized as a large vessel
      vasculitis. The first diagnostic criteria for TA were developed by Ishikawa in
      1988 and modified by Sharma et al., in 1995. Two sets of classification criteria
      were developed for TA to include patients in epidemiologic studies and clinical
      trials: the 1990 ACR Classification Criteria for TA and the Classification
      Criteria for childhood TA proposed by the European League Against Rheumatism
      (EULAR), the Pediatric Rheumatology European Society (PRES) and by the Pediatric
      Rheumatology International Trials Organization (PRINTO) to be used for patients
      younger than 18 years. The Diagnostic and Classification Criteria in Vasculitis
      Study (DCVAS) is an international effort that is under way to develop a single
      classification system and a validated set of diagnostic criteria for systemic
      vasculitides using data-driven methods.

PMID- 24461382
TI  - Criteria for Behcet's disease with reflections on all disease criteria.
AB  - With no specific histologic, laboratory or imaging features the
      diagnosis/classification of Behcet's Disease (BD) remains clinical. As such,
      disease criteria are needed. The International Study Group Criteria set is the
      most widely used. It has some limitations, especially in telling BD from Crohn's
      disease. On the other hand the main issue, as it also applies to many of the
      other criteria sets in rheumatology, is our lack of appreciation of a list of
      misconceptions--some examples of which are unluckily also found in the 2010
      ACR/EULAR RA Criteria set--about diagnostic/classification criteria making and
      their implementation. 1. The view that classification and diagnostic criteria
      should be different is ill advised in that the cerebral/arithmetic basis of both
      are the same. 2. The default promise of diagnostic criteria to come once we
      formulate a classification criteria set is an extension of the previous
      misconception. 3.Taking pains to avoid circularity in criteria making is
      unwarranted since the essence of criteria making is circular. In addition we fail
      to exploit the utility of the disease criteria in ruling out, rather than ruling
      in, the diseases we seek. Finally we also fail to appreciate the paramount
      importance of the Bayesian prior (the pretest) probability in formulating and
      implementing these disease criteria. To formulate criteria tailored to
      subspecialties, as well as giving the often forgotten family history more
      importance in our criteria sets are some ways to improve the prior probability on
      which our diagnostic/classification decisions will be based. We first have to
      reconcile with ourselves that probabilities are very important in our practice
      and research. Moreover that reconciliation must also be shared with the public,
      which includes our patients.

PMID- 24461383
TI  - Diagnosis and classification of juvenile idiopathic arthritis.
AB  - In recent years, it has become increasingly clear that the term Juvenile
      Idiopathic Arthritis (JIA) comprises not one disease but several. Moreover,
      recent studies strongly suggest that some of these clinico-pathophysiologic
      entities appear to cross current diagnostic categories. The ultimate goal of the
      JIA classification is to facilitate development of better, more specific therapy
      for different forms of disease though improved understanding of pathophysiology.
      The past two decades have witnessed significant advances in treatment and
      improved outcomes for many children with chronic arthritis. However,
      understanding of the basic biologic processes underlying these diseases remains
      far from complete. As a result, even the best biologic agents of today represent
      "halfway technologies". Because they do not treat fundamental biologic processes,
      they are inherently expensive, need to be given for a long time in order to
      ameliorate the adverse effects of chronic inflammation, and do not cure the
      disease. Pediatric rheumatology is now entering an era in which diagnostic
      categories may need to change to keep up with discovery. A more precise,
      biologically based classification is likely to contribute to development of more
      specific and improved treatments for the various forms of childhood arthritis. In
      this review, we discuss how genetic, gene expression, and immunologic findings
      have begun to influence how these diseases are understood and classified.

PMID- 24461384
TI  - Diagnostic criteria of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a multisystem disease characterized by vascular
      abnormalities, immune system activation manifested by SSc-specific autoantibodies
      and disturbances in fibroblast function. The clinical manifestations are highly
      heterogeneous and commonly include skin thickening, Raynaud's phenomenon, digital
      ulcers, gastroesophageal reflux disease, interstitial lung disease and cardiac
      diastolic dysfunction. The diagnosis of SSc in a patient with typical end-organ
      disease is relatively straight-forward, but is unsatisfactory because it implies
      that the diagnosis is delayed until irreversible tissue damage is present.
      Diagnostic criteria are generally designed to facilitate the clinical process and
      to allow early institution of therapy to relieve symptoms and possibly prevent
      irreversible damage. Several attempts at defining diagnostic criteria for SSc
      have been made in the past. Raynaud's phenomenon, SSc-specific autoantibodies and
      nailfold capillary abnormalities are among the most promising items likely to be
      retained in a final set of diagnostic criteria. The EULAR Scleroderma Trial and
      Research group (EUSTAR) is currently in the process of prospectively validating a
      set of diagnostic criteria for the very early diagnosis of SSc and results are
      expected in 2015. 

PMID- 24461385
TI  - Diagnostic criteria for systemic lupus erythematosus: a critical review.
AB  - Systemic lupus erythematosus is a multi-organ system autoimmune disease with
      clinical and serological heterogeneity. The formulation of initial criteria for
      SLE was first proposed by the American College of Rheumatology and appeared in
      1971. Although the original purpose of the criteria was to classify the disease,
      it became widely used as a diagnostic criteria in clinical situations. Since then
      the ACR criteria have undergone at least two changes (in 1982 and 1997). Clinical
      manifestations that can differentiate SLE patients from healthy people such as
      skin lesions, arthritis, renal disorder, neurologic disorder, hematologic changes
      and others are included in these criteria. Serum anti-nuclear antibody, anti-ds
      DNA antibody and anti-Sm antibody are important biomarkers of SLE patients. In
      2012, the Systemic Lupus Collaborating Clinics proposed the SLICC criteria for
      SLE in view of new knowledge of autoantibodies and the importance of low
      complement. Future biomarkers may be useful in distinguishing SLE from other
      diseases and in monitoring of disease activity. 

PMID- 24461386
TI  - The diagnosis and classification of giant cell arteritis.
AB  - Giant-cell arteritis (GCA) involves the major branches of the aorta with
      predilection for the extracranial branches of the carotid artery. It occurs in
      individuals older than 50 years and the incidence increases with age. The signs
      and symptoms of giant cell arteritis can be classified into four subsets: cranial
      arteritis, extracranial arteritis, systemic symptoms and polymyalgia rheumatica.
      Patients may develop any combination of these manifestations, associated with
      laboratory evidence of an acute-phase reaction. The only test that confirms GCA
      diagnosis is a temporal artery biopsy, showing vasculitis with mononuclear cell
      inflammatory infiltrates, often with giant cells. Due to the focal and segmental
      nature of the infiltrates, areas of inflammation may be missed by the biopsy and
      the histological examination is normal in about 15% of the cases. Some imaging
      modalities may aid in the diagnosis of GCA. Among those, color duplex
      ultrasonography of the temporal arteries is more commonly used. There are no
      independent validating criteria to determine whether giant cell arteritis is
      present when a temporal artery biopsy is negative. The American College of
      Rheumatology criteria for the classification of giant cell arteritis may assist
      in the diagnosis. However, meeting classification criteria is not equivalent to
      making the diagnosis in individual patients, and the final diagnosis should be
      based on all clinical, laboratory, imaging and histological findings.
      Glucocorticoids are the treatment of choice for GCA. The initial dose is 40-60
      mg/day for most uncomplicated cases. Addition of low-dose aspirin (100 mg/d) has
      been shown to significantly decrease the rate of vision loss and stroke during
      the course of the disease.

PMID- 24461387
TI  - The diagnosis and classification of mixed connective tissue disease.
AB  - The term "mixed connective tissue disease" (MCTD) concerns a systemic autoimmune
      disease typified by overlapping features between two or more systemic autoimmune
      diseases and the presence of antibodies against the U1 small nuclear
      ribonucleoprotein autoantigen (U1snRNP). Since the first description of this
      condition in 1972, the understanding of clinical manifestations and long-term
      outcome of MCTD have significantly advanced. Polyarthritis, Raynaud's phenomenon,
      puffy fingers, lung involvement and esophageal dysmotility are the most
      frequently reported symptoms among the different cohorts during the course of the
      disease. Moreover, in recent years a growing interest has been focused on severe
      organ involvement such as pulmonary arterial hypertension and interstitial lung
      disease which can accrue during the long-term follow-up and can still
      significantly influence disease prognosis. Over the last years, significant
      advances have been made also in disease pathogenesis understanding and a central
      pathogenetic role of anti-U1RNP autoantibodies has clearly emerged. Although
      controversies on disease definition and classification still persist, MCTD
      identifies a group of patients in whom increased surveillance for specific
      manifestations and prognostic stratification became mandatory to improve
      patient's outcomes. 

PMID- 24461388
TI  - The diagnosis and classification of microscopic polyangiitis.
AB  - Microscopic Polyangiitis (MPA) is a small vessel vasculitis. The disease is
      defined by the 2012 revised Chapel Hill Consensus Conference Nomenclature of
      Vasculitides [1] as necrotizing vasculitis, with few or no immune deposits,
      predominantly affecting small vessels (i.e. capillaries, venules, or arterioles).
      Necrotizing arteritis involving small and medium arteries may be present.
      Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often
      occurs. Granulomatous inflammation is absent. MPA belongs to the ANCA-associated
      vasculitides (AAV). ANCA in MPA are predominantly directed against
      myeloperoxidase (MPO-ANCA) but may, in a minority of patients, be directed
      against proteinase 3 (PR3-ANCA). Not all patients, however, have ANCA.
      Microscopic polyangiitis (MPA) belongs to the anti-neutrophil cytoplasmic
      antibody (ANCA)-associated vasculitides. MPA is clinically characterized by small
      vessel vasculitis primarily affecting the kidneys and the lungs but other organs
      may be involved as well. Renal involvement, which can be the only manifestation,
      is clinically apparent as rapidly progressive glomerulonephritis and
      histopathologically as pauci-immune necrotizing and crescentic
      glomerulonephritis. ANCA in MPA are mainly directed to myeloperoxidase (MPO
      ANCA). Besides their diagnostic significance, MPO-ANCA appear pathogenic in MPA.
      Rituximab with steroids is at least as effective as cyclophosphamide with
      steroids for induction of remission. 

PMID- 24461389
TI  - A qualitative exploratory study of nursing students' assessment of the
      contribution of palliative care learning.
AB  - OBJECTIVE: We explored the contribution of optional palliative care (PC) learning
      to the training of undergraduate nursing students. DESIGN: This is a qualitative,
      exploratory study. PARTICIPANTS: PC students from two universities (n=236)
      responded to the open question: What was the contribution of the PC course to
      your training? METHODS: A thematic analysis of the respondents' answers was
      performed with investigator triangulation. FINDINGS: Four themes were identified.
      Firstly, the PC course provided a comprehensive view of the nursing discipline.
      Secondly, the course helped the students to know how to interact with,
      communicate with and better understand patients. Thirdly, the contribution of the
      course to the students' personal growth prompted them to reflect personally on
      death, thus promoting self-awareness. Finally, the students considered the PC
      course to be of great importance in the nursing curriculum. CONCLUSION: Nursing
      students believed that a PC course was an essential component in their training,
      which contributed favourably to their personal and professional development.

PMID- 24461390
TI  - Unconscious influences on decision making in blindsight.
AB  - Newell & Shanks (N&S) argue that an explanation for blindsight need not appeal to
      unconscious brain processes, citing research indicating that the condition merely
      reflects degraded visual experience. We reply that other evidence suggests
      blindsighters' predictive behavior under forced choice reflects cognitive access
      to low-level visual information that does not correlate with visual
      consciousness. Therefore, while we grant that visual consciousness may be
      required for full visual experience, we argue that it may not be needed for
      decision making and judgment. 

PMID- 24461392
TI  - [Macrophage activation syndrome: rare complication of murine typhus].
AB  - INTRODUCTION: Typhi is one of the rickettsial species endemic in the
      Mediterranean countries and is associated with the zoonotic infection of murine
      typhus, which may have a complicated course especially in adult patients. The
      association with macrophage activation syndrome (MAS) has rarely been reported in
      the medical literature. CASE REPORT: We describe a case of murine typhus in a
      diabetic woman complicated with MAS, who was effectively treated with cyclin and
      parenteral immunoglobulin. CONCLUSION: The murine typhus can be exceptionally
      complicated with SAM. This infection should be suspected in front of the
      discovery of SAM.

PMID- 24461391
TI  - [Association between bone turnover markers, bone mineral density and vitamin D in
      Moroccan postmenopausal women].
AB  - The aim of the study is to find the correlation between bone turnover markers and
      bone mineral density in a cohort of Moroccan postmenopausal women. PATIENTS AND
      METHODS: A cross-sectional study, conducted over a period of 12 months from
      October 2008 to November 2009. Five hundred Moroccan postmenopausal women
      volunteers participated in this study and we included only 185. RESULTS: In this
      cohort of 185 women, average age 60 years, the percentage of osteoporotic women
      was 35.7%, they were older 62.09 (9.13) years and they had an average of the body
      mass index (BMI), the lowest 29.58 (4.45). The values of the bone mineral density
      (BMD) measured at the lumbar spine correlated positively and significantly with
      BMI (P<0.001), serum calcium (P=0.026), negatively with age (P<0.001) and
      osteocalcin (OC) (P=0.0033). As for the results of BMD measured at the femoral
      neck, they show a negative and highly significant correlation with age (P<0.001)
      and osteocalcin. Looking for an association between the biochemical markers of
      bone remodeling, a weak positive correlation was found between the calcium (Ca)
      and alkaline phosphatase (PAL) on the one hand and Ca and intact parathyroid
      hormone (PTHi) in the other hand. And a significant positive correlation was
      found between PTHi and PAL, and between PTHi and OC. Finally, a significant
      positive correlation was found between the cross-laps (beta-CTX) and Ca and
      between PAL and OC. CONCLUSION: Our results are in agree to some international
      studies and disagree to others.

PMID- 24461393
TI  - Prevalence, identification by a DNA microarray-based assay of human and food
      isolates Listeria spp. from Tunisia.
AB  - OBJECTIVES: We aimed at evaluating the prevalence of Listeria species isolated
      from food samples and characterizing food and human cases isolates. MATERIAL AND
      METHODS: Between 2005 and 2007, one hundred food samples collected in the markets
      of Tunis were analysed in our study. Five strains of Listeria monocytogenes
      responsible for human listeriosis isolated in hospital of Tunis were included.
      Multiplex PCR serogrouping and pulsed field gel electrophoresis (PFGE) applying
      the enzyme AscI and ApaI were used for the characterization of isolates of L.
      monocytogenes. We have developed a rapid microarray-based assay to a reliable
      discrimination of species within the Listeria genus. RESULTS: The prevalence of
      Listeria spp. in food samples was estimated at 14% by using classical biochemical
      identification. Two samples were assigned to L. monocytogenes and 12 to L.
      innocua. DNA microarray allowed unambiguous identification of Listeria species.
      Our results obtained by microarray-based assay were in accordance with the
      biochemical identification. The two food L. monocytogenes isolates were assigned
      to the PCR serogroup IIa (serovar 1/2a). Whereas human L. monocytogenes isolates
      were of PCR serogroup IVb, (serovars 4b). These isolates present a high
      similarity in PFGE. Food L. monocytogenes isolates were classified into two
      different pulsotypes. These pulsotypes were different from that of the five
      strains responsible for the human cases. CONCLUSION: We confirmed the presence of
      Listeria spp. in variety of food samples in Tunis. Increased food and clinical
      surveillance must be taken into consideration in Tunisia to identify putative
      infections sources.

PMID- 24461394
TI  - Sublethal toxicity of carbofuran pesticide on the African catfish Clarias
      gariepinus (Burchell, 1822): hematological, biochemical and cytogenetic response.
AB  - The present work aimed to evaluate the toxic effects of two sublethal
      concentrations of carbofuran pesticide (0.16 and 0.49mg/L, for 35 days) on
      hematological and blood biochemical parameters of catfish, Clarias gariepinus,
      and to evaluate the genotoxic potential of carbofuran on the erythrocytes of C.
      gariepinus for the first time by micronucleus and erythrocyte alteration assays.
      The results revealed a significant (p<0.05) decrease in red blood cells (RBCs)
      count, haemoglobin (Hb) concentration, haematocrit (Hct) and the mean corpuscular
      haemoglobin concentration (MCHC) levels, but the mean corpuscular volume (MCV)
      and the mean corpuscular haemoglobin (MCH) levels were increased. White blood
      cells (WBCs) count, neutrophils, eosinophils, basophils and monocytes were
      increased significantly (p<0.05), while the lymphocytes were decreased. Also,
      carbofuran exposure caused a significant (p<0.05) increase in aspartic
      aminotransferase (AST) and alanine aminotransferase (ALT) and a significant
      (p<0.05) decrease in alkaline phosphatase (ALP) activity. The results obtained
      showed a significant (p<0.05) increase in plasma glucose, total lipids, urea and
      creatinin levels, but the total protein, albumin concentration and globulin
      levels were decreased (p<0.05) significantly and consequently A/G ratio also
      decreased. Carbofuran caused many genotoxic and morphological alterations in
      erythrocytes such as formation of micronuclei (MN), echinocytes, acanthocytes,
      tear like drop cells, microcytes and erythrocytes with vacuolated cytoplasm and
      pale nucleus. The exposed groups have shown significant variations in frequencies
      of MN and altered erythrocytes in comparison to control group, and these
      frequencies increased significantly (p<0.05) with the increase of carbofuran
      concentration. Therefore, current results present a clear evidence of the
      response of C. gariepinus to carbofuran and allow us to consider that C.
      gariepinus as a good bioindicator to reflect the toxicity and the genotoxic
      potential of carbofuran that might be released into the aquatic ecosystems. 

PMID- 24461395
TI  - Comparison between prescription of regular or on-demand ibuprofen on
      postoperative pain after single-visit root canal treatment of teeth with
      irreversible pulpitis.
AB  - INTRODUCTION: Pain management is very important in endodontic practice. The aim
      of this study was to compare the effect on pain relief of on-demand versus
      regular prescription of ibuprofen after single-visit root canal treatment in
      teeth with irreversible pulpitis. METHODS: Sixty mandibular and maxillary molar
      teeth with irreversible pulpitis without spontaneous pain had single-visit root
      canal treatment. After this treatment, patients were randomly allocated to 2
      groups of 30 patients each. Patients in group 1 received a single dose of 400 mg
      ibuprofen and a rescue bag of the same medication to use if they felt pain and
      needed further medication. Patients in group 2 received the same medication as
      group 1 patients after treatment, and they were also provided with a prescription
      to use 400 mg ibuprofen every 6 hours for at least 24 hours. The patients were
      asked to rate their pain on a visual analog scale for up to 48 hours after
      treatment. The data were analyzed with Mann-Whiney, chi-square, Fisher exact, and
      McNemar tests. RESULTS: Two patients were excluded because they did not return
      their pain record forms. Data analysis of the remaining 58 patients showed no
      significant difference in pain felt by the patients in groups 1 and 2 at either
      24 or 48 hours after treatment (P = .849 and P = .732, respectively). Patients in
      group 2 used significantly more medication compared with patients in group 1 (P =
      .04). CONCLUSIONS: In patients who had irreversible pulpitis with no moderate to
      severe spontaneous pain, prescribing ibuprofen on a regular basis after root
      canal treatment had no significant effect on pain relief compared with an on
      demand regimen up to 48 hours after treatment.

PMID- 24461396
TI  - Overlapping protective and destructive regulatory pathways in apical
      periodontitis.
AB  - INTRODUCTION: Protective and destructive immunoreactions take place
      simultaneously in apical periodontitis. However, the same reactions defending the
      periapical area from infection-derived damage may also result in host tissue
      injury. METHODS: The inflammatory reaction of the periapical tissues is self
      limited. Regeneration of the injured tooth-supporting structures may follow
      elimination of the causative microbial irritation. RESULTS: Recent experimental
      and clinical observations have identified important interplay between positive
      and negative regulatory pathways. A network of stimulatory and inhibitory
      feedback loops may influence the intensity of the defense and inflammatory
      responses and the balance between bone resorption and regeneration, resulting in
      lesion expansion or healing of apical periodontitis. CONCLUSIONS: We critically
      discuss research data on regulatory mechanisms that control the activity of host
      effector cells and signaling molecules during interactions with pathogenic
      microbes.

PMID- 24461397
TI  - Association between chronic apical periodontitis and coronary artery disease.
AB  - INTRODUCTION: Studies have shown that periodontal disease is independently
      associated with coronary artery disease. However, this same association has not
      been demonstrated with chronic apical periodontitis. The goal of this study was
      to establish the relationship between chronic apical periodontitis and coronary
      artery disease. METHODS: This cross-sectional study included 103 patients who
      underwent coronary angiography at the University Hospital Presidente Dutra,
      Federal University of Maranhao, Sao Luis-Maranhao, Brazil. The patients answered
      a structured questionnaire and underwent physical and laboratory examinations.
      For each patient, a full-mouth set of periapical radiographs was taken. To
      compare numerical data, Student's t test for independent samples or the Mann
      Whitney U test (nonparametric) was used. The homogeneity of variance was assessed
      by using Levene's test. For comparison of categorical data, the chi-square test
      or Fisher's exact test was used. The logistic regression analysis was performed
      to identify the independent predictors of coronary artery disease. The criterion
      for statistical significance was set at 5%. Statistical analysis was conducted by
      using SAS version 6.11 software. RESULTS: The study comprised 103 patients (52
      men, 51 women; mean age, 61.9 years); 31.1% were literate, and 55.3% were
      married. In the study sample, the prevalence of chronic apical periodontitis was
      41.7% and of coronary artery disease, it was 65%. The patients with chronic
      apical periodontitis had a 2.79 times higher risk of developing coronary artery
      disease. CONCLUSIONS: In these study patients, chronic apical periodontitis was
      independently associated with coronary artery disease.

PMID- 24461398
TI  - Polymorphism of the CD14 and TLR4 genes and post-treatment apical periodontitis.
AB  - INTRODUCTION: This study investigated the association of CD14 -260C>T and TLR4
      +896A>G gene polymorphisms with post-treatment apical periodontitis in Brazilian
      individuals. METHODS: The study population consisted of 41 patients with post
      treatment apical periodontitis and 42 individuals with root canal-treated teeth
      exhibiting healed/healing periradicular tissues (controls). All teeth had apical
      periodontitis lesions at the time of treatment, which was completed at least 1
      year previously. Saliva was collected from the participants; DNA was extracted
      and used for CD14 and TLR4 genotyping using the polymerase chain reaction
      restriction fragment length polymorphism approach and a real-time polymerase
      chain reaction TaqMan assay (Applied Biosystems, Foster City, CA), respectively.
      RESULTS: No specific genotype or allele of the CD14 and TLR4 genes or any
      combination thereof was positively associated with post-treatment apical
      periodontitis (P > .05). CONCLUSIONS: Data from the present study suggest that
      polymorphisms in the CD14 and TLR4 genes do not influence the response to
      endodontic treatment of teeth with apical periodontitis.

PMID- 24461399
TI  - Evaluation of root canal configuration of maxillary molars in a Brazilian
      population using cone-beam computed tomographic imaging: an in vivo study.
AB  - INTRODUCTION: The aim of this study was to analyze and characterize root canal
      morphology of maxillary molars of the Brazilian population using cone-beam
      computed tomographic (CBCT) imaging. METHODS: Patients referred for a CBCT
      radiographic examination for accurate diagnosis and treatment planning were
      enrolled in the study. A total of 620 healthy, untreated, fully developed
      maxillary first and second molars were included (314 first molars and 306 second
      molars). The following observations were recorded: (1) number of roots and their
      morphology, (2) number of canals per root, (3) fused roots, and (4) primary
      variations in the morphology of the root canal systems. RESULTS: First and second
      molars showed a higher prevalence of 3 separate roots, mesiobuccal, distobuccal,
      and palatal, with 1 canal in each root (52.87% and 45.09%, respectively). Two
      canals in the mesiobuccal roots represented 42.63% of teeth, whereas mesiobuccal
      roots of second molars presented 2 canals in 34.32%. The most common anatomic
      variation in the maxillary first molar was related to the root canal
      configuration of the mesiobuccal root, whereas the root canal system of the
      maxillary second molar teeth showed more anatomic variables. CONCLUSIONS:
      Mesiobuccal roots of maxillary molar teeth had more variation in their canal
      system than the distobuccal or palatal roots. The root canal configuration of the
      maxillary second molars was more variable than the first molars in a Brazilian
      population. CBCT imaging is a clinically useful tool for endodontic diagnosis and
      treatment planning.

PMID- 24461400
TI  - Quantification of endotoxins in infected root canals and acute apical abscess
      exudates: monitoring the effectiveness of root canal procedures in the reduction
      of endotoxins.
AB  - INTRODUCTION: This clinical study was conducted to measure the endotoxin levels
      in infected root canals (RCs) and exudates related to acute apical abscesses
      (AAAs). In addition, the effectiveness of RC procedures in reducing the endotoxin
      levels in RCs was monitored. METHODS: Paired samples of infected RCs and exudates
      from AAAs were collected from 10 subjects by using paper points. RCs samples were
      collected before (RCS1) and after chemomechanical preparation (CMP) (RCS2), after
      17% EDTA (RCS3), and after 30 days of intracanal medication (Ca[OH]2 +
      chlorhexidine) (RCS4). A turbidimetric kinetic limulus amebocyte lysate assay was
      used for the measurement of endotoxins. RESULTS: Endotoxins were detected in 100%
      of the baseline samples of AAAs and RCs (RCS1) with median values of 175 EU/mL
      and 41.5 EU/mL, respectively (P < .05). After CMP (RCS2), endotoxins were reduced
      to a median value of 0.54 EU/mL (P < .05). Subsequent irrigation with EDTA (RCS3)
      failed to present a significant effectiveness in reducing the endotoxin levels
      (median= 0.37 EU/mL) (P = .07). However, intracanal medication for 30 days (RCS4)
      reduced endotoxins to median values of 0.03 EU/mL (P < .01). CONCLUSIONS: The
      present study revealed a strong association between the high levels of endotoxins
      found in AAAs and RCs collected from the same tooth. Moreover, the effectiveness
      of CMP in reducing the endotoxin levels from RCs in acute endodontic infection
      was improved by the use of RC medication.

PMID- 24461401
TI  - Periapical status related to the quality of coronal restorations and root
      fillings in a Korean population.
AB  - INTRODUCTION: The purpose of this study was to assess the prevalence of apical
      periodontitis in root canal-treated teeth from the Korean population and to
      evaluate the relationship between the quality of root canal fillings and coronal
      restorations and the periapical status of these teeth. METHODS: Full-mouth
      periapical radiographs at the Dental Hospital of Yonsei University, Seoul, South
      Korea, were examined. A total of 1030 endodontically treated teeth restored with
      full veneer crown-type restorations were evaluated by 2 independent examiners.
      Teeth were classified as healthy or diseased according to the periapical status.
      The quality of endodontic treatment and coronal restorations were also classified
      via radiographic and clinical evaluation. The data were analyzed using the chi
      square test and logistic regression. RESULTS: Forty-one percent of all
      endodontically treated teeth were classified as diseased. Approximately 35.6% of
      the teeth had endodontic treatments that were rated as adequate. The diseased
      teeth rate for cases with adequate endodontic treatment was 24.5%, which was
      significantly lower when compared with teeth with inadequate endodontic treatment
      (49.9%). The number of teeth with adequate coronal restorations was 706 (68.5%).
      Teeth with adequate coronal restorations had a significantly decreased prevalence
      of diseased teeth (34.7%) compared with teeth with inadequate coronal
      restorations (54.3%). Teeth with both adequate root fillings and restorations
      showed a significantly better outcome (82.3%) than the others, and teeth with
      both inadequate root fillings and restorations showed a significantly worse
      outcome (41.2%) than the others. CONCLUSIONS: Data from this Korean population
      showed a relatively high prevalence of apical periodontitis. The quality of
      endodontic treatment and coronal restorations were of equal importance and were
      strong independent predictors of the periapical status.

PMID- 24461402
TI  - Treatment decisions in 330 cases referred for apical surgery.
AB  - INTRODUCTION: Apical surgery is an important treatment option for teeth with
      postendodontic apical periodontitis. However, little information is available
      regarding treatment planning in cases referred for apical surgery. This study
      evaluated the decisions made in such cases and analyzed the variables influencing
      the decision-making process. METHODS: The study retrospectively assessed clinical
      and radiographic data of 330 teeth that had been referred to a specialist in
      apical surgery with regard to the treatment decisions made in those teeth. The
      clinical and radiographic variables were divided into subcategories to analyze
      which factors influenced the decision-making process. RESULTS: The treatment
      decisions included apical surgery (59.1%), tooth extraction (25.8%), no treatment
      (9.1%), and nonsurgical endodontic retreatment (6.1%). Variables that showed
      statistically significant differences comparing treatment decisions among
      subcategories included probing depth (P = .001), clinical attachment level (P =
      .0001), tooth mobility (P = .012), pain (P = .014), clinical signs (P = .0001),
      length (P = .041) and quality (P = .026) of the root canal filling, and size (P =
      .0001) and location (P = .0001) of the periapical lesion. CONCLUSIONS: This study
      shows that apical surgery was the most frequently made treatment decision in
      teeth referred to a specialist in apical surgery, but every fourth tooth was
      considered nonretainable and was scheduled for extraction. The data showed that
      the most common variables that influenced the decision to extract teeth were
      teeth with an increased probing depth and tooth mobility and teeth presenting
      with lesions not located at the apex.

PMID- 24461403
TI  - Regenerative potential of immature permanent teeth with necrotic pulps after
      different regenerative protocols.
AB  - INTRODUCTION: Regenerative endodontics is a promising alternative treatment for
      immature teeth with necrotic pulps. The present study was performed to assess the
      regenerative potential of young permanent immature teeth with necrotic pulp after
      the following treatment protocols: (1) a mineral trioxide aggregate (MTA) apical
      plug, (2) the regenerative endodontic protocol (blood clot scaffold), and (3) the
      regenerative endodontic protocol with a blood clot and an injectable scaffold
      impregnated with basic fibroblast growth factor. METHODS: Immature necrotic
      permanent maxillary central incisors (n = 36) of patients 9-13 years old were
      divided into 3 groups according to the treatment protocol: the MTA group (MTA
      apical plug), the REG group (regenerative endodontic protocol [blood clot]), and
      the FGF group (regenerative endodontic protocol [blood clot + injectable
      scaffold]). Follow-up was done up to 18 months. Standardized radiographs were
      digitally evaluated for an increase in root length and thickness, a decrease in
      the apical diameter, and a change in periapical bone density. RESULTS: After a
      follow-up period of 18 months, most of the cases showed radiographic evidence of
      periapical healing. Groups 2 and 3 showed a progressive increase in root length
      and width and a decrease in apical diameter. CONCLUSIONS: The regenerative
      endodontic procedure allowed the continued development of roots in teeth with
      necrotic pulps. The use of artificial hydrogel scaffold and basic fibroblast
      growth factor was not essential for repair.

PMID- 24461404
TI  - Higher expression of galectin-3 and galectin-9 in periapical granulomas than in
      radicular cysts and an increased toll-like receptor-2 and toll-like receptor-4
      expression are associated with reactivation of periapical inflammation.
AB  - INTRODUCTION: Cysts and periapical granulomas are inflammatory reactions that
      develop in response to periapical infection by microbial species in dental root
      canal. It is known that toll-like receptors (TLRs) are pathogen recognition
      molecules and that galectins are lectins that can be associated with the
      inflammatory process, stimulating or inhibiting the immune system. The objective
      of this study was to evaluate the in situ expression of TLRs and galectins in
      radicular cysts and periapical granulomas. METHODS: We analyzed 62 cases (30
      radicular cysts, 27 periapical granulomas, and 5 control cases). Indirect
      immunohistochemistry was used to evaluate the expression of TLRs (TRL-2 and TLR
      4) and galectins (Gal-3 and Gal-9). RESULTS: The expression of Gal-3 and Gal-9
      was significantly higher in periapical granulomas and radicular cysts than in the
      control group. Similarly, both Gal-3 and Gal-9 were expressed significantly more
      in periapical granulomas than in radicular cysts. The expression of TLR-2 was
      significantly higher in periapical granulomas and radicular cysts than in the
      control group, and it was also significantly higher in radicular cysts with sinus
      tract than in the cases without sinus tract. Furthermore, the expression of TLR-4
      was significantly higher in the cases of periapical granulomas with sinus tract
      than in the cases without sinus tract. CONCLUSIONS: Gal-3/Gal-9 and TLR-2/TLR-4
      expression in the periapical granulomas and radicular cysts is associated with
      reactive periapical inflammation. Pathobiology of periapical disease is a very
      complex interplay of many bioactive molecules involved in immunoinflammatory
      responses. Up-regulation of these bioactive molecules might be an important
      modulator of inflammatory periapical lesions.

PMID- 24461405
TI  - Follow-up survey of general dentists to identify characteristics associated with
      increased referrals to endodontists.
AB  - INTRODUCTION: A 2009 American Association of Endodontists survey of dentists in
      general practice (GPs) to assess their perceptions and understand the factors
      associated with referrals to endodontists was the first of its kind. The American
      Association of Endodontists repeated the survey in 2012 to update our
      understanding of the referral behavior of GPs by reexamining the effects of
      endodontist characteristics and professional behavior and the role of GP
      demographics and perceptions in determining referrals to endodontists. METHODS:
      Researchers conducted a cross-sectional study that included a quantitative online
      survey of 786 GPs in the United States (14% of 5737 initially opened invitations)
      from November 1-13, 2012. RESULTS: Ninety-four percent of the GPs had positive
      perceptions of endodontists, but they referred only 43% of patients who required
      root canal treatment to endodontists. The perception that endodontists are
      partners in patient care and endodontic services are worth the cost was strongly
      related to the likelihood of referring (P < .05). GPs rated referring patients
      back for restorative treatment (95%, n = 734), timely follow-up of reports and
      images (94%, n = 726), and patient scheduling accommodation (91%, n = 707) as
      effective ways to build partnerships. Gender and years in practice moderated the
      relationships between several predictors (eg, communication, value of treatment,
      and expertise) and the likelihood of referring. CONCLUSIONS: There are concrete
      actions that endodontists can take and segments of the GP population that can be
      targeted to successfully address the issue of increasing referrals. However,
      examining the role of endodontist actions and GP perceptions and demographics is
      just the beginning in addressing the relationships involved in referral behavior.

PMID- 24461406
TI  - Development of a new in vitro methodology to simulate internal root resorption.
AB  - INTRODUCTION: Studies to evaluate the diagnostic power of imaging examinations to
      detect root resorption have been based on simulations produced by burs.
      Standardized, round, and well-outlined access cavities do not reproduce the
      characteristics of physiological lesions and may facilitate diagnosis, masking
      the true accuracy of imaging techniques. A methodology to simulate internal root
      resorption by using acid demineralization was developed. METHODS: Eleven
      extracted single-rooted teeth were mesiodistally sectioned into homologous
      halves. Root canals were labeled to ensure restricted and controlled action of
      fluids. The protocol was composed of 24-hour cycles (5% nitric acid for 12 hours,
      rinsing with deionized water, and 8% sodium hypochlorite for 10 minutes). At the
      end of each cycle 1 tooth was removed from treatment, defining an exposure time
      that cumulated to the last tooth. Electron microscopy imaging was assessed to
      determine lesion area and depth. RESULTS: Minimum and maximum and areas and
      depths were 3.14 mm2 and 10.34 mm2 and 0.22 mm and 1.59 mm, respectively.
      Resorption simulated by the protocol proposed reproduced lesions of different
      sizes. CONCLUSIONS: The irregular shape and larger diameter:depth ratio suggest
      that these lesions are more similar to in vivo internal root resorption, compared
      with bur-induced lesions.

PMID- 24461407
TI  - Lysophosphatidic acid rescues human dental pulp cells from ischemia-induced
      apoptosis.
AB  - INTRODUCTION: Dental pulp is particularly susceptible to ischemic conditions
      (hypoxia and serum deprived) because it is commonly exposed to trauma,
      inflammation, chronic caries injury, and pulpitis. We investigated the apoptotic
      response of human dental pulp cells (HDPCs) to varying levels of oxygen and serum
      to mimic different degrees of ischemia, tested whether lysophosphatidic acid
      (LPA) could reverse ischemia-induced apoptosis, and investigated the possible
      mechanisms of LPA. METHODS: HDPCs were cultured under conditions mimicking serum
      deprivation and ischemia for 2 days with or without LPA at 25 MUg/mL. Flow
      cytometry and JC-1 fluorescence were used to detect any apoptotic change. Western
      blotting was used to measure the expression of the apoptosis regulators B-cell
      lymphoma 2 (Bcl-2) and Bax, focal adhesion kinase (FAK), Src, extracellular
      signal-regulated kinase (ERK), and Akt. RESULTS: Flow cytometry and JC-1
      immunofluorescence showed that ischemia could induce apoptosis of HDPCs in 2 days
      and treatment with LPA could reduce cell death significantly. To clarify the
      molecular mechanisms, Western blot results showed up-regulation of both
      proapoptotic Bax and antiapoptotic Bcl-2 during apoptosis. LPA functioned as an
      antiapoptotic cytokine by activation of the phosphorylation of FAK and ERK. No
      statistically significant difference was found in the activation levels of p-Src
      or p-Akt. CONCLUSIONS: A self-defense mechanism functioned during cell apoptosis.
      LPA could effectively rescue HDPCs from ischemia-induced apoptosis via regulation
      of Bax and Bcl-2 and the activation of phosphorylated FAK and phosphorylated ERK.
      LPA is a potent candidate for biological therapy of chronic pulpal inflammatory
      diseases.

PMID- 24461411
TI  - Preservation of bacterial DNA by human dentin.
AB  - INTRODUCTION: The capacity of dentin and collagen to bind DNA and protect against
      spontaneous and nuclease-induced degradation was evaluated individually and by
      the incubation of DNA with nuclease-producing bacteria in a mixed culture.
      METHODS: Extracted Fusobacterium nucleatum DNA was incubated with dentin shavings
      or collagen for 90 minutes. The DNA-bound substrates were incubated in different
      media (water, sera, and DNase I) for up to 3 months. Amplifiable DNA was released
      from dentin using EDTA,or from collagen using proteinase K, and evaluated by
      polymerase chain reaction (PCR). The stability of dentin-bound DNA was also
      assessed in a mixed culture (Parvimonas micra and Pseudoramibacter alactolyticus)
      containing a DNase-producing species, Prevotella intermedia. Samples were
      analyzed for amplifiable DNA. RESULTS: In water, dentin-bound DNA was recoverable
      by PCR at 3 months compared with no detectable DNA after 4 weeks in controls (no
      dentin). DNA bound to collagen was detectable by PCR after 3 months of incubation
      in water. In 10% human sera, amplifiable DNA was detectable at 3 months when
      dentin bound and in controls (no dentin). In mixed bacterial culture, dentin
      bound DNA was recoverable throughout the experimental period (3 months), compared
      with no recoverable F. nucleatum DNA within 24 hours in controls (no dentin).
      CONCLUSIONS: There is a strong binding affinity between DNA and dentin, and
      between DNA and serum proteins or collagen. These substrates preserve DNA against
      natural decomposition and protect DNA from nuclease activity, factors that may
      confound molecular analysis of the endodontic microbiota yet favor
      paleomicrobiological studies of ancient DNA.

PMID- 24461412
TI  - Fibrin gel improves tissue ingrowth and cell differentiation in human immature
      premolars implanted in rats.
AB  - INTRODUCTION: In pulpless immature human premolars implanted in rodents, this
      study investigated whether fibrin gel offered advantages over leaving the root
      canal empty regarding soft tissue ingrowth and cell differentiation. METHODS:
      Root canals of extracted human immature premolars (n = 12) were accessed and then
      irrigated with 5% sodium hypochlorite followed by 17% ethylenediaminetetraacetic
      acid. Root canals were then either left empty or filled with a fibrin gel (n = 6
      each) before being placed subcutaneously on top of the calvarial bone of rats (1
      tooth per rat) for 12 weeks. After sacrifice, teeth were histologically assessed.
      Tissue ingrowth was quantified and compared between groups using the Mann-Whitney
      U test (P < .05). Cells adhering to the pulp canal wall were
      immunohistochemically screened for the presence of bone sialoprotein (BSP) and
      dentin sialoprotein (DSP). RESULTS: More tissue grew into the pulp space when
      teeth were filled with fibrin gel (P < .05). The presence of fibrin gel affected
      not only the extent of tissue ingrowth but also tissue morphology and
      differentiation of cells contacting the dentinal wall. In the fibrin gel group,
      newly formed tissue was similar to normal pulp, constituted of inner pulp, cell
      rich zone, cell-free zone, and an apparent odontoblast layer, which stained
      positive for BSP and DSP. Newly formed blood vessels were also more abundant
      compared with the initially empty root canals. CONCLUSIONS: Under the conditions
      of this study, fibrin gel improved cell infiltration and cell-dentin interaction.
      Both are necessary for pulp tissue regeneration.

PMID- 24461408
TI  - Antibiotic resistance and capacity for biofilm formation of different bacteria
      isolated from endodontic infections associated with root-filled teeth.
AB  - INTRODUCTION: To date, a variety of microbial species have been isolated from
      endodontic infections. However, endodontic clinical bacterial isolates have not
      been sufficiently characterized with regard to their capacity for antibiotic
      resistance and biofilm formation. In this study, antibiotic resistance and
      biofilm formation of 47 different aerobic and anaerobic bacterial isolates,
      belonging to 32 different species previously isolated from infected filled root
      canals, were studied. METHODS: Antibiotic sensitivity to 11 antibiotics including
      penicillin G, amoxicillin, clindamycin, gentamicin, vancomycin, tetracycline,
      doxycycline, fosfomycin, rifampicin, ciprofloxacin, and moxifloxacin was tested
      using the standardized Etest method (Bio Merieux, Marcy-1'Etoile, France). The
      antibiotic sensitivity of 4 control strains was also estimated in parallel.
      Additionally, the capacity to form biofilms was quantified using the microtiter
      plate test. RESULTS: Different aerobic and anaerobic bacterial species were
      either resistant against a number of antibiotics or showed high minimal
      inhibitory concentrations against clinically relevant antibiotics. Five aerobic
      and 2 anaerobic isolates, including Enterococcus faecalis, Streptococcus mutans,
      Lactobacillus fermentum, Actinomyces naeslundii, Actinomyces viscosus, Prevotella
      buccae, and Propionibacterium acidifaciens, were characterized as being high
      biofilm producers, whereas 8 aerobic and 3 anaerobic isolates were found to be
      moderate biofilm producers. Most isolates with resistance or markedly high
      minimal inhibitory concentration values were also either moderate biofilm
      producers or high biofilm producers. CONCLUSIONS: These results suggest that the
      clinical significance of endodontic infections could include that they serve as a
      reservoir for antibiotic resistance. Furthermore, endodontic treatment should
      consider the adhesion and biofilm formation by a variety of bacteria.

PMID- 24461409
TI  - A novel GuttaFlow sealer supports cell survival and attachment.
AB  - INTRODUCTION: The purpose of this in vitro study was to compare the
      biocompatibility of a novel formulation of a silicone-based endodontic sealer
      GuttaFlow 2 (GF2; Coltene/Whaledent, Langenau, Germany) with the original (GFO)
      and fast-set (GFF) formulations of GuttaFlow and with an epoxy resin sealer,
      AHPlus Jet (AH+J; Dentsply, York, PA). METHODS: Sealers were set into 3 * 5.5 mm
      discs. Cell culture media was used to extract leachable products at 24 hours and
      1, 2, and 4 weeks. Primary human periodontal ligament fibroblasts were incubated
      with sealer elutes for 24 hours and evaluated using the 3-(4, 5-dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide assay and the calcein AM assay. Cell
      attachment was evaluated on set sealer that was either rinsed or unrinsed with
      cell media for 1 week. Statistical analysis was performed using the Student t
      test. RESULTS: Both calcein and 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide assays revealed that periodontal ligament cell
      viability was reduced on AH+J at 1, 2, and 4 weeks compared with all GuttaFlow
      sealers. There were no differences in cell viability between the GuttaFlow
      samples, and all displayed high rates of cell survival at all time periods. After
      2 hours, cell attachment to the rinsed GFO and GFF samples exceeded the control,
      and at 24 hours cell attachment on all GuttaFlow samples exceeded the control.
      AH+J sealers supported significantly less cell attachment when compared with all
      GuttaFlow sealers. Cell attachment to set sealers showed better cell attachment
      when rinsed compared with unrinsed. CONCLUSIONS: GuttaFlow sealers were more
      biocompatible than AHJ in vitro. The novel GF2 displayed comparable
      biocompatibility with GFF and GFO.

PMID- 24461410
TI  - The role of integrin-alpha5 in the proliferation and odontogenic differentiation
      of human dental pulp stem cells.
AB  - INTRODUCTION: It has been reported that integrin-alpha5 (ITGA5) activity is
      related to cell proliferation, differentiation, migration, and organ development.
      However, the involvement of ITGA5 in the biological functions of human dental
      pulp stem cells (hDPSCs) has not been explored. The aim of this study was to
      investigate the role of ITGA5 in the proliferation and odontogenic
      differentiation of hDPSCs. METHODS: We knocked down ITGA5 in hDPSCs using
      lentivirus-mediated ITGA5 short hairpin RNA (shRNA). Changes in the proliferation
      in hDPSCs infected with lentiviruses expressing ITGA5-specific shRNA or negative
      control shRNA were examined using the 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine labeling.
      Both ITGA5 knockdown cells and shMock cells were cultured in mineralization
      medium for 3 weeks, and the differentiation of cells was detected with alizarin
      red S staining. The expression of odontogenic differentiation-related molecular
      markers was assessed using real-time polymerase chain reaction and Western blot
      assays. RESULTS: The knockdown of ITGA5 decreased the proliferation capacity of
      hDPSCs. ITGA5 shRNA promoted odontogenic differentiation of hDPSCs with the
      enhanced formation of mineralized nodules. It also up-regulated the messenger RNA
      expression of multiple markers of odontogenesis and the expression of dentin
      sialophosphoprotein protein. CONCLUSIONS: These findings suggest that ITGA5 plays
      an important role in maintaining hDPSCs in a proliferative state. The inhibition
      of ITGA5 signaling promotes the odontogenic differentiation of hDPSCs.

PMID- 24461418
TI  - Interference of electronic apex locators with implantable cardioverter
      defibrillators.
AB  - INTRODUCTION: The purpose of this in vitro study was to evaluate the potential
      electromagnetic interference of electronic apex locators (EALs) on implantable
      cardioverter defibrillators (ICDs). METHODS: Four different EALs were tested for
      their ability to interfere with the correct function of 3 different ICDs. Each
      ICD was placed in a plastic container with 1.5 L physiological saline, and the
      EAL unit was placed at a distance of 2.5 cm from the ICD. The file electrode and
      lip clip were placed directly against the ICD. The EAL was turned on for 30
      seconds while continuously showing the "APEX" mark. As a negative control, the
      ICD was tested without EAL for 30 seconds. An electrosurgical unit served as a
      positive control. During each test, the ICD output was monitored continuously by
      real-time telemetry, and after completion of the experiment, intracardiac
      electrocardiograms were printed. The tests were repeated 3 times for each device.
      The electrocardiograms were examined for interference on ICD ventricular
      activity. RESULTS: All EALs tested and the negative control failed to produce
      electromagnetic interference in each of the ICDs tested. The electrosurgical unit
      induced interference in the ICDs, which were detected as episodes of ventricular
      tachycardia and led to the initiation of electrical shocks in all ICDs.
      CONCLUSIONS: The 4 EALs tested did not interfere with the correct functioning of
      ICDs in vitro.

PMID- 24461419
TI  - Apical enlargement according to different pecking times at working length using
      reciprocating files.
AB  - INTRODUCTION: The purpose of this study was to evaluate the apical preparation
      sizes resulting from repetitive pecking motions at the working length (WL) by
      using reciprocating files. METHODS: Sixty simulated endodontic training blocks
      with a J-shaped root canal were instrumented using Reciproc R25 (VDW, Munich,
      Germany) or WaveOne Primary (Dentsply Maillefer, Ballaigues, Switzerland) (n = 30
      each). Each group was divided into 3 subgroups based on the repetitive pecking
      times at the WL: 1, 2, and 4 times. All specimens were prepared by 1 operator who
      was competent in instrumenting canals with both file systems. All of the
      procedures, including the WL measurement, were performed under an operating
      microscope. The replica of the prepared canal was taken with silicone impression
      material. After 24 hours of allowing the impression to set, each sample was
      evaluated under a scanning electron microscope at the apical tip, and the apical
      preparation size (diameter) was measured at the D0 level of the impression. The
      data were analyzed statistically using 2-way analysis of variance and the Tukey
      post hoc test at P = .05. RESULTS: The mean diameter (MUm) varied between 253 and
      274 and between 258 and 277 for Reciproc and WaveOne, respectively, without
      significant differences. However, more repetitive pecking motions at the WL
      resulted in a significantly larger apical preparation size than the subgroups
      with less pecking times (P < .05). CONCLUSIONS: Under the conditions of this
      study, the results indicate that a greater number of repetitive pecking times at
      the WL may result in an apical preparation size that is larger than the actual
      file size.

PMID- 24461413
TI  - Radiopacity and cytotoxicity of Portland cement containing zirconia doped bismuth
      oxide radiopacifiers.
AB  - INTRODUCTION: This study evaluates the radiopacity and cytotoxicity of Portland
      cements containing a radiopacifier of bismuth oxide (Bi2O3) with yttria
      stabilized zirconia (YSZ) dopant. METHODS: Various radiopacifier powders of Bi2O3
      with 0%, 15%, 30%, and 100% YSZ dopant were prepared by solid-state reaction at
      700 degrees C for 12 hours and characterized by x-ray diffraction. Portland
      cement/radiopacifier/calcium sulfate (75/20/5) were mixed and set by deionized
      water. Changes in radiopacity and in vitro cell viability of the hydrated cements
      were assessed. An average of 6 measured equivalent thickness of aluminum (N = 6)
      capable of producing similar radiographic density was recorded. The cytotoxicity
      of each material was determined in MC3T3 E1 cell-based methyl-thiazol-tetrazolium
      assay. RESULTS: The x-ray diffraction patterns of YSZ doped Bi2O3 are different
      from those of pure Bi2O3 and YSZ. The cement-containing radiopacifier of
      Bi2O3/YSZ (85/15) presented significantly greater radiopacity (P < .05) compared
      with pure Bi2O3. The mouse osteoblastic cell (MC3T3-E1) viabilities of these 2
      groups were statistically similar (P < .05). CONCLUSIONS: The radiopacifier of
      Bi2O3/YSZ (85/15) reveals higher radiopacity but similar cell viability when
      compared with pure Bi2O3. It shows potential use as an alternative radiopacifier
      in root-end filling materials.

PMID- 24461424
TI  - Putting value in biomarker research and reporting.

PMID- 24461415
TI  - Solubility and disintegration of new calcium aluminate cement (EndoBinder)
      containing different radiopacifying agents.
AB  - INTRODUCTION: The aim of this study was to evaluate the solubility and
      disintegration of EndoBinder (EB) containing 3 different radiopacifying agents,
      bismuth oxide (Bi2O3), zinc oxide (ZnO), or zirconium oxide (ZrO2), in comparison
      with gray mineral trioxide aggregate (GMTA) and white MTA (WMTA). METHODS: Ten
      specimens of each cement were made in a stainless steel matrix (20 * 1.5 mm)
      according to Specification no. 57 of American National Standards
      Institute/American Dental Association: EB + Bi2O3, EB + ZrO, EB + ZnO, WMTA, and
      GMTA. The specimens were weighed on an accurate analytical scale and immersed in
      50 mL distilled and deionized water at 37 degrees C for 7 days. Afterwards,
      specimens were dried and weighed again to determine mass loss (%). Resulting
      solutions were analyzed in an atomic absorption spectrophotometer for
      identification and quantification of chemical elements released. RESULTS: All
      cements presented mean values of solubility and disintegration above the American
      National Standards Institute/American Dental Association Specification no. 57. EB
      + Bi2O3 presented the lowest mass loss (5.08%) and WMTA (6.65%) the highest, with
      no statistically significant difference (P > .05). The release of several
      chemical elements was observed, mostly metal ions. Only GMTA and EB + Bi2O3
      showed the presence of Cr, with significant difference (P < .05). EB + ZnO
      presented the highest levels of Pb, followed by WMTA (P < .05). For As, the
      cements presented different release levels, with EB + ZnO showing the highest and
      GMTA the lowest levels (P < .05). However, the amounts of As and Pb released were
      lower than the safe limit proposed by ISO 9917-1. CONCLUSIONS: Irrespective of
      the radiopacifying agents used, EndoBinder presented similar behavior to MTA.

PMID- 24461427
TI  - Roxarsone and its metabolites in chicken manure significantly enhance the uptake
      of As species by vegetables.
AB  - Roxarsone is an organoarsenic feed additive which can be finally degraded to
      other higher toxic metabolites after excreted by animal. In this work, the uptake
      of As species by vegetables treated with chicken manure bearing roxarsone and its
      metabolites was investigated. It was showed that more than 96% of roxarsone added
      in chicken feed was degraded and converted to arsenite, monomethylarsonic acid,
      dimethylarsinic acid, arsenate, 4-hydroxyphenylarsonic acid and other unknown As
      species. Arsenite and arsenate could be found in roots of vegetables but only
      arsenite transported up to shoots. Chicken manure bearing roxarsone and its
      metabolites increased 33-175% of arsenite and 28% ~ seven times of arsenate in
      vegetable roots, 68-175% of arsenite in edible vegetable shoots. Arsenite, the
      most toxic As form, was the major extractable As species in vegetables accounted
      for 79-98%. The results reflected that toxic element As could be absorbed by
      vegetables via the way: roxarsone in feed -> animal -> animal manure -> soil ->
      crop and the uptake of As species would be enhanced by using chicken manure
      bearing roxarsone and its metabolites as organic fertilizer.

PMID- 24461417
TI  - Assessing accumulated hard-tissue debris using micro-computed tomography and free
      software for image processing and analysis.
AB  - INTRODUCTION: The accumulation of debris occurs after root canal preparation
      procedures specifically in fins, isthmus, irregularities, and ramifications. The
      aim of this study was to present a step-by-step description of a new method used
      to longitudinally identify, measure, and 3-dimensionally map the accumulation of
      hard-tissue debris inside the root canal after biomechanical preparation using
      free software for image processing and analysis. METHODS: Three mandibular molars
      presenting the mesial root with a large isthmus width and a type II Vertucci's
      canal configuration were selected and scanned. The specimens were assigned to 1
      of 3 experimental approaches: (1) 5.25% sodium hypochlorite + 17% EDTA, (2)
      bidistilled water, and (3) no irrigation. After root canal preparation, high
      resolution scans of the teeth were accomplished, and free software packages were
      used to register and quantify the amount of accumulated hard-tissue debris in
      either canal space or isthmus areas. RESULTS: Canal preparation without
      irrigation resulted in 34.6% of its volume filled with hard-tissue debris,
      whereas the use of bidistilled water or NaOCl followed by EDTA showed a reduction
      in the percentage volume of debris to 16% and 11.3%, respectively. The closer the
      distance to the isthmus area was the larger the amount of accumulated debris
      regardless of the irrigating protocol used. CONCLUSIONS: Through the present
      method, it was possible to calculate the volume of hard-tissue debris in the
      isthmuses and in the root canal space. Free-software packages used for image
      reconstruction, registering, and analysis have shown to be promising for end-user
      application.

PMID- 24461422
TI  - A rare root canal configuration of bilateral maxillary first molar with 7 root
      canals diagnosed using cone-beam computed tomographic scanning: a case report.
AB  - INTRODUCTION: The complexity of the root canal system of maxillary molars
      presents a constant challenge in the diagnosis and treatment of these teeth. This
      case report describes the importance of a surgical operating microscope and cone
      beam computed tomographic (CBCT) imaging. METHODS: Root canal treatment of a left
      maxillary first molar with 3 roots and 7 canals was successfully performed. Seven
      canals were identified with the help of a surgical operating microscope and CBCT
      imaging. CBCT images also confirmed the 3 roots and 7 canals in the right
      maxillary first molar. RESULTS: CBCT images confirmed a type IV canal pattern in
      the distal and palatal root, whereas the mesial root had a type VIII canal
      pattern. CONCLUSIONS: The use of a surgical operating microscope and CBCT imaging
      helps the clinician to diagnose unusual anatomy of a tooth and facilitate
      successful endodontic treatment.

PMID- 24461423
TI  - [Use of misoprostol for induction of labor in case of fetal death or termination
      of pregnancy during second or third trimester of pregnancy: Efficiency, dosage,
      route of administration, side effects, use in case of uterine scar].
AB  - OBJECTIVE: Study, based on the literature, of the use of misoprostol for
      induction of labor in cases of second or third trimester fetal death or
      termination of pregnancy and define the different mode of administration.
      MATERIALS AND METHODS: Bibliographic review using the Medline and Pubmed
      databases and the guidelines of the international professional societies.
      Selection of papers in French and English. Keywords used: misoprostol,
      termination of pregnancy, mid and third trimester, scarred uterus, previous
      cesarean section, uterine rupture. RESULTS: Misoprostol is effective for
      induction of labor in case of second or third fetal death or termination of
      pregnancy. Comparing to oral route, vaginal route reduces the induction-expulsion
      time and the rate of patients remaining undelivered in the first 24 hours without
      increasing side effects. Oral route is a possible alternative if preferred by the
      patient. Sublingual route seems interesting but data are limited. The use of
      moderate doses (800-2400 MUg/day) every 3 to 6 hours seems to be the best
      compromise between efficiency and tolerance. It is not possible to recommend a
      specific dosing schedule. The risk of uterine rupture in case of previous
      cesarean section justifies the use of minimum effective dose for these patients.
      In this case, it is recommended not to exceed a dose of 100 MUg for each dose.
      The induction-birth period and doses of misoprostol required to induce labor are
      reduced when combined with mifepristone administered 36 to 48 hours before.
      CONCLUSION: Misoprostol is effective and safe for induction of labor in case of
      second or third trimester fetal death or termination of pregnancy.

PMID- 24461425
TI  - The neurological effects of prenatal and postnatal mercury/methylmercury exposure
      on three-year-old children in Taiwan.
AB  - This study attempts to elucidate the relationship between neurological effects
      and mercury/methylmercury concentrations in various biomarkers, including
      meconium, hair, fingernail, and toenail. Eight-three mother-infant pairs were
      recruited between August 2008 and December 2009, and follow-up examinations on
      these children were completed after three years. The Bayley Scales of Infant and
      Toddler Development (Bayley-III) for evaluating the cognitive, language, and
      motor development of three-year-old children were calculated and validated. The
      geometric mean of the total mercury concentration in meconium was 89.6 ng g(-1).
      The methylmercury concentrations in hair, fingernail, and toenail samples were
      1.96, 0.64, and 0.55 MUg g(-1), respectively. Seventy percent of children had
      hair methylmercury concentrations exceeding the U.S. environmental protection
      agency (EPA) reference of 1 MUg g(-1). A significantly positive correlation was
      obtained between methylmercury levels in hair, fingernail, and toenail. These
      methylmercury levels were also significantly positively correlated with the
      children's fish intake and negatively correlated with a Bayley-III scale score of
      expressive language. The prenatal mercury exposure, however, did not show
      significant influence on neurological development. High fish consumption appears
      to be a critical risk factor for methylmercury levels in children and may cause a
      lower expressive language score.

PMID- 24461420
TI  - Evaluation of the antibacterial efficacy of silver nanoparticles against
      Enterococcus faecalis biofilm.
AB  - INTRODUCTION: The purpose of this study was to evaluate the antibacterial
      efficacy of silver nanoparticles (AgNPs) as an irrigant or medicament against
      Enterococcus faecalis biofilms formed on root dentin. METHODS: Dentin sections
      were inoculated with E. faecalis for 4 weeks to establish a standard monospecies
      biofilm model. These biofilms were tested in 2 stages. In stage 1, the biofilms
      were irrigated with 0.1% AgNP solution, 2% sodium hypochlorite, and sterile
      saline for 2 minutes, respectively. In stage 2, the biofilms were treated with
      AgNP gel (0.02% and 0.01%) and calcium hydroxide for 7 days. The ultrastructure
      of one half of the specimens from each group was evaluated by using scanning
      electron microscopy, whereas the structure and distribution of viable bacteria of
      the other half of the specimens were assessed with confocal laser scanning
      microscopy combined with viability staining. RESULTS: Syringe irrigation with
      0.1% AgNP solution did not disrupt the biofilm structure, and the proportion of
      viable bacteria in the biofilm structures was not different from that of the
      saline group (P > .05) but was less than that of the control group (P < .05). The
      biofilms treated with 0.02% AgNP gel as medicament significantly disrupted the
      structural integrity of the biofilm and resulted in the least number of post
      treatment residual viable E. faecalis cells compared with 0.01% AgNP gel and
      calcium hydroxide groups (P < .05). CONCLUSIONS: The findings from this study
      suggested that the antibiofilm efficacy of AgNPs depends on the mode of
      application. AgNPs as a medicament and not as an irrigant showed potential to
      eliminate residual bacterial biofilms during root canal disinfection.

PMID- 24461426
TI  - Nonextractable residue formation of sulfonamide antimicrobials: new insights from
      soil incubation experiments.
AB  - Soil incubation experiments using (14)C-labelled sulfamethazine were carried out
      to assess the factors governing its nonextractable residue (NER) formation via
      nucleophilic addition reactions. Circumstantial evidence on possible mechanisms
      of NER formation was derived from a selective manipulation of soil samples. The
      amount of quinones in soil available for nucleophilic addition was a limiting
      factor as indicated by (i) an (initial) increase of NER formation by adding
      quinone precursors or enhancing their formation by manganese oxide addition and
      (ii) a decrease of NER formation by limiting the formation of quinones under
      anaerobic conditions. A slow NER formation with time under aerobic conditions is
      likely caused by covalent bonding as well, because no slow NER formation phase
      was observed under anaerobic conditions. 

PMID- 24461428
TI  - Concentrations of mercury in tissues of striped dolphins suggest decline of
      pollution in Mediterranean open waters.
AB  - The Mediterranean is a semi-enclosed sea subject to high mercury (Hg) pollution
      from both natural and anthropogenic sources. With the objective of discerning
      temporal changes in marine Hg pollution in the oceanic waters of the northwestern
      Mediterranean Sea, we analysed liver and kidney from striped dolphins (Stenella
      coeruleoalba) collected during 2007-2009 and compared them with previous results
      from a similar sample from 1990-1993. The effect of body length and sex on tissue
      Hg concentrations was investigated to ensure an unbiased comparison between the
      periods. The Hg concentrations did not show significant sex-related differences
      in any tissue or period but were correlated positively with body length. Using
      body length as a covariate, Hg concentrations in liver and kidney were higher in
      1990-1993 than in 2007-2009. This result suggests that measures to reduce
      emissions in Western European countries have been effective in reducing mercury
      pollution in Mediterranean open waters. 

PMID- 24461416
TI  - The effects of Mtwo, R-Endo, and D-RaCe retreatment instruments on the incidence
      of dentinal defects during the removal of root canal filling material.
AB  - INTRODUCTION: The aim of this study was to compare the incidence of dentinal
      defects after retreatment procedures with different nickel-titanium rotary
      retreatment files. METHODS: One hundred-eighty mandibular premolars were randomly
      assigned to 6 groups (n = 30 teeth per group). One group was left unprepared, and
      the remaining 5 groups were prepared with K-files (Dentsply Maillefer,
      Ballaigues, Switzerland) and filled with gutta-percha and AH plus sealer
      (Dentsply Maillefer, Ballaigues, Switzerland). Of these 5 groups, 1 group was
      left filled and received no further treatments; in the other groups, removal of
      the filling material was performed with Mtwo R (VDW, Munich, Germany), D-RaCe
      (FKG Dentaire, La Chaux-de-Fonds, Switzerland), R-Endo instruments (Micro-Mega,
      Besancon, France), or Hedstrom files (Dentsply Maillefer). Roots were then
      sectioned 3, 6, and 9 mm from the apex and observed under a microscope. The
      presence of dentinal defects was noted. Chi-square tests were performed to
      compare the incidence of dentinal defects between the groups. A Pearson
      correlation test was performed to check the correlation between defects and root
      level or remaining dentin thickness. RESULTS: No defects were observed in the
      unprepared group. Dentinal defects were detected in all retreatment groups.
      Retreatment groups showed significantly more defects than the filled but no
      retreatment group (P < .05). There was no significant difference in the
      occurrence of defects between retreatment groups (P > .05). There was no
      correlation between the appearance of defects and level of the root or remaining
      dentin thickness. CONCLUSIONS: Under the experimental conditions, all retreatment
      techniques used in this study created defects in the root dentin.

PMID- 24461421
TI  - Histologic and histobacteriologic observations of failed
      revascularization/revitalization therapy: a case report.
AB  - INTRODUCTION: Mechanical debridement plays an important role in eliminating
      intracanal bacteria, such as biofilm on the canal walls and bacteria in the
      dentinal tubules. Mechanical debridement is not recommended for root canal
      disinfection in revascularization/revitalization therapy. Here we report a failed
      revascularization/revitalization case, which could be due to inadequate root
      canal disinfection without mechanical removal of biofilm and bacteria in dentinal
      tubules. METHODS: A 6-year-old boy had a traumatic injury to tooth #9, which was
      avulsed and replanted within 40 minutes. The tooth subsequently developed a local
      swelling in the periapical area. The patient was referred to the Postgraduate
      Endodontic Clinic for revascularization/revitalization therapy on tooth #9. The
      treated tooth remained asymptomatic for 16 months and then developed pain and
      local periapical swelling. The oral surgeon extracted the
      revascularized/revitalized tooth. On request, the extracted tooth was processed
      for histologic and histobacteriologic examination. RESULTS: The tissue in the
      canal was completely destroyed. Most bacteria were observed in the apical portion
      and not in the coronal portion of the canal and formed biofilm on the canal walls
      and penetrated into the dentinal tubules. CONCLUSIONS: On the basis of
      histobacteriologic observations, the failure of revascularized/revitalized tooth
      could be due to inadequate root canal disinfection without mechanical
      debridement. It may be important to perform mechanical debridement as part of the
      revascularization/revitalization therapy to disrupt the biofilm on the canal
      walls and remove bacteria in the dentinal tubules because
      revascularization/revitalization therapy is able to increase thickening of the
      canal walls.

PMID- 24461430
TI  - Photodegradation-based detection of fluorescent whitening agents in a mountain
      river.
AB  - Fluorescent whitening agents (FWAs) are highly soluble and poorly biodegradable
      ingredients used in laundry detergents and in industries (paper, textile, plastic
      manufacturing). They are likely to pass through biological wastewater treatment
      systems. The presence of FWAs in a mountain river was detected by monitoring the
      decay of synchronous fluorescence intensity at lambda(ex)=360 nm after exposing
      samples to ultraviolet (UV) light (365 nm), for mimicking sunlight, for 15 min.
      The method was first validated on four commercial FWAs (DAS-1, FB28, DMA-X and
      CBS-X) in different water matrices (deionized water and pristine river water in
      the presence of humic acid and dyes). A 40% decay was observed after 15 min for
      the least photosensitive FWA (CBS-X). A field application was then performed on
      samples collected along a mountain river in which impacts of FWAs from domestic
      sources (laundry greywater) and industrial sources (paper and textile mills) were
      suspected. Variations of fluorescence decay at lambda(ex)=360 nm could be
      explained by these potential sources of pollution. It is suggested that the
      fluorescence decay at lambda(ex)=280 nm also be considered as an indicator, as
      some FWAs can exhibit fluorescence at that excitation wavelength.

PMID- 24461434
TI  - [Exacerbations of asthma: A demonstration that guidelines are insufficiently
      followed].

PMID- 24461435
TI  - [Which practice in respiratory medicine in 2025? How to prepare?].

PMID- 24461436
TI  - [Pulmonary function tests in COPD].

PMID- 24461437
TI  - [Asthma in words, ... from Homerus to GINA].

PMID- 24461414
TI  - In vitro biocompatibility and oxidative stress profiles of different hydraulic
      calcium silicate cements.
AB  - INTRODUCTION: MTA Plus is a new calcium silicate cement with unknown cytotoxicity
      characteristics. The objectives of this study were to examine the effect of MTA
      Plus on the viability, apoptosis/necrosis profile, and oxidative stress levels of
      rat odontoblast-like cells. METHODS: MDPC-23 cells were exposed to gray and white
      MTA Plus (GMTAP, WMTAP), gray and white ProRoot MTA (GMTA, WMTA) cements, or
      their eluents. The cells were evaluated for (1) cell viability by using XTT
      assay, (2) apoptosis/necrosis by using flow cytometry and confocal laser scanning
      microscopy, and (3) oxidative stress by measuring reactive oxygen species.
      RESULTS: XTT assay showed that all test cements exhibited marked initial
      cytotoxicity that decreased with time. By the end of the third week, GMTAP and
      GMTA were comparable to untreated cells (negative control) in terms of cell
      viability, whereas WMTAP and WMTA were significantly lower than the untreated
      cells. Apoptosis/necrosis profiles of cells exposed to WMTAP and GMTAP were not
      significantly different from untreated cells, whereas cells exposed to WMTA and
      GMTA showed significantly less viable cells. All experimental groups exhibited
      reduction of intracellular reactive oxygen species formation compared with
      untreated cells, although cells exposed to WMTA were not significantly different
      from untreated cells. CONCLUSIONS: Both the gray and white versions of MTA Plus
      possess negligible in vitro cytotoxic risks that are time and dilution dependent.
      They enrich the spectrum of hydraulic calcium silicate cements currently
      available to clinicians for endodontic applications.

PMID- 24461431
TI  - Diffuse rhabdomyomatosis presenting as infantile hypertrophic cardiomyopathy.

PMID- 24461429
TI  - Contrasting effects of two antimicrobial agents (triclosan and triclocarban) on
      biomineralisation of an organophosphate pesticide in soils.
AB  - We examined the impact of triclosan (TCS) and triclocarban (TCC) antimicrobial
      compounds on the biomineralisation of glucose and cadusafos pesticide in three
      Australian soils. Mineralisations of radiolabelled ((14)C) compounds were
      measured over a period of up to 77 d in sterile and non-sterile soils treated
      with different concentrations of TCS and TCC (0-450 mg kg(-1)). The rates of
      mineralisation of cadusafos were found to decrease with increasing concentration
      of TCS in all soils, but varied with soil type. Soils treated with TCS at the
      highest concentration (270 mg kg(-1)) reduced cadusafos mineralisation by up to
      58%. However, glucose mineralisation was not significantly affected by the
      presence of TCS. While TCS, significantly reduced the mineralisation of cadusafos
      (by 17%; p<0.05) even at the lowest studied concentration (30 mg kg(-1)), no
      significant effect of TCC was observed on cadusafos or glucose mineralisation
      even at the highest concentration used (450 mg kg(-1)).

PMID- 24461433
TI  - Clinical and pathological heterogeneity of a congenital disorder of glycosylation
      manifesting as a myasthenic/myopathic syndrome.
AB  - Congenital disorders of glycosylation are often associated with muscle weakness
      in apparent isolation or as part of a multi-systemic disorder. We report here the
      clinical and pathological features resulting from a homozygous mutation of ALG2
      in an extended family. Phenotypic heterogeneity is observed among the small
      cohort of patients reported to date and is highlighted by our study. Linkage
      analysis, homozygozity mapping and whole exome sequencing followed clinical and
      pathological characterization of patients who presented with a congenital limb
      girdle pattern of weakness with no ocular or bulbar involvement. Nerve
      stimulation studies were consistent with a congenital myasthenic syndrome.
      Severity and progression of disease was variable. Muscle biopsies showed
      myopathic features, ragged red fibers and a sub-sarcolemmal accumulation of
      structurally normal mitochondria. Whole exome sequencing revealed an indel
      mutation c.214_224delGGGGACTGGCTdelinsAGTCCCCG, p.72_75delGDWLinsSPR in exon 1 of
      ALG2. Mutation of ALG2 manifested as a limb girdle pattern of muscle weakness
      with defects at both the neuromuscular junction and sarcomere. In addition the
      accumulation and distribution of mitochondria in the diseased muscle and the
      presence of ragged red fibers were supportive of a mitochondrial myopathy. ALG2
      mutation results in a heterogeneous phenotype and care should be taken in
      categorization and treatment of these patients. 

PMID- 24461439
TI  - [Residents in respiratory medicine: Assessment of the course and wishes regarding
      their career].
AB  - INTRODUCTION: The aim of this study was to assess the feelings of residents in
      respiratory medicine regarding the quality and organization of their training and
      towards their career prospects. METHODS: A prospective survey conducted over the
      Internet among all the members of the French Young Pulmonologists Association
      (AJPO2). RESULTS: One hundred and thirty-two (71.5%) members responded. The
      rating given to theoretical training was 6 [5-7] whereas the practical training
      was rated at 7 [6-8] out of 10. The majority of the residents considered that the
      length of their course should be adapted (80.3%). Of them, 74.2% wanted to add a
      mandatory semester. The proposed mandatory semester was in bronchoscopy (40.3%).
      Seventy-two percent of the resident wanted to acquire a specialisation, the most
      common of which was in oncology (36.6%). Among the residents, 96.2% wanted to
      conduct a fellowship. The main reason for this was their feeling of inability to
      correctly handle patients at the end of their residency. Of the residents, 55.3%
      were considering working in a public hospital. CONCLUSION: There are
      opportunities to improve the French respiratory residency training both in its
      theory and practical aspects. The modalities of this training could also be
      adapted. Access to a fellowship is a major concern for the residents.

PMID- 24461438
TI  - [Characteristics of admissions to pediatric emergency departments for
      exacerbations of asthma. Assessment and prospects for improving prehospital
      care].
AB  - INTRODUCTION: The frequency of emergency department visits for asthma is a major
      public health problem in pediatrics. The aim of this study is to establish the
      characteristics of children visiting pediatric emergency departments for acute
      asthma and to assess their therapeutic management prior to admission. METHODS: A
      prospective clinical study performed during 3 months at the pediatric emergency
      department of the university teaching hospital of Clermont-Ferrand, of children
      aged 1 to 16 years admitted to the department with a clinical diagnosis of asthma
      exacerbation. RESULTS: One hundred and forty-three patients were included in the
      study. Asthma crises were moderate to severe in 69.2% of cases (n=99). Initial
      therapeutic management prior to the admission to the emergency department was
      appropriate in 17.5% of cases (n=25). Most of the known asthmatic patients had
      not been followed up by a pediatric pulmonologist (n=56). A crisis protocol had
      been set up in 16.5% of cases (n=20). Exacerbations were more severe among
      younger patients (P=0.002) and economically disadvantaged children (P=0.025).
      CONCLUSIONS: This study uncovers poor knowledge of the disease among asthmatic
      children and their families, and an insufficient awareness among health
      practitioners of current recommendations for the treatment of asthmatic children.
      Admissions to the emergency department for asthma could be partly avoided by
      improving diagnosis and therapeutic education.

PMID- 24461441
TI  - [Assessment of recent weight history before instituting continuous positive
      airways pressure in a cohort of patients with severe obstructive sleep
      apnoea/hypopnea syndrome].
AB  - OBJECTIVES: The aim of this study is to evaluate the recent weight history in
      patients with the obstructive sleep apnoea/hypopnoea syndrome (OSAHS) needing
      treatment with continuous positive airways pressure (CPAP). PATIENTS AND METHODS:
      Over a period of 18 months, a self-administered questionnaire concerning recent
      weight history was given to patients during the installation of CPAP. RESULTS:
      The study population consisted of 1337 patients. An increase in weight of at
      least 5% over the 5 years preceding the institution of CPAP was found in 44% of
      patients. This increase was moderate (5-10%), important (10-20%) and very
      important (>20%) in respectively 12.3%, 16.1% and 15.6% of patients. The patients
      with important or very important weight gain differed from those whose weight
      remained steady in a higher percentage of women, young people, and patients with
      a higher prevalence of obesity, persistent smoking, a history of venous
      thromboembolism and treatment with anti-depressants. CONCLUSION: A recent
      increase in weight is frequently seen in severe OSAHS and is associated with some
      clinical characteristics.

PMID- 24461432
TI  - Functional and computed tomographic evolution and survival of restrictive
      allograft syndrome after lung transplantation.
AB  - BACKGROUND: Restrictive allograft syndrome (RAS) has recently been defined as a
      novel phenotype of chronic lung allograft dysfunction (CLAD) after lung
      transplantation. The goal was to describe computed tomographic (CT) changes of
      RAS patients and to correlate this with spirometry and survival. METHODS: All 24
      established RAS patients at our center were retrospectively included. CT scans
      from pre-CLAD, CLAD, post-CLAD and late-CLAD subjects were systematically
      evaluated by a blinded observer using a semi-quantitative scoring system. Changes
      in CT patterns were correlated with spirometry and survival. RESULTS: The most
      prominent CT features at diagnosis of CLAD as compared with pre-CLAD were
      appearance of central (p = 0.020) and peripheral ground glass opacities (p =
      0.052), as well as septal and non-septal lines (p = 0.020). Survival after
      diagnosis of CLAD was only associated with the absolute value of forced vital
      capacity (FVC) at diagnosis (R = 0.46 and p = 0.021), and not with any CT
      alterations. Evolution of CT abnormalities after diagnosis of CLAD included
      significant increases in (traction) bronchiectasis (p < 0.0001), central (p =
      0.051) and peripheral (p = 0.0002) consolidation, architectural deformation (p =
      0.0002), volume loss (p = 0.0004) and hilus retraction (p = 0.0036). The absolute
      FVC decrease post-CLAD diagnosis correlated with CT alterations. CONCLUSIONS: In
      the early stages of RAS, central and peripheral ground glass opacities are the
      most prominent feature on CT, whereas, in later stages, bronchiectasis, traction,
      central and peripheral consolidation, architectural deformation, volume loss and
      hilus retraction are more pronounced. CT changes, however, could not predict
      survival, whereas FVC at diagnosis of CLAD seems to be the best predictor of
      survival.

PMID- 24461442
TI  - [Use of sedation in the palliative care situation by respiratory physicians].
AB  - INTRODUCTION: The prognosis of advanced stage chronic lung disease, including
      lung cancer, is often poor and associated with uncomfortable symptoms for the
      patient, especially in the end of life phase. In the case of intolerable
      symptoms, refractory to maximal treatment, sedation may then be considered. This
      is sometimes a source of confusion and difficulty for clinicians who need to know
      the official guidelines. The purpose of this study was to investigate the use of
      sedation by respiratory physicians, in order to understand their difficulties in
      these complex situations. METHOD: The study was conducted using semi-structured,
      anonymous interviews of volunteers. The topics discussed included their
      definition of sedation, its indications, their possible difficulties or
      reluctance in using it, the information given to the patient and the traceability
      of the sedation prescription. RESULTS: All respiratory physicians agreed to
      participate in the study, indicating a major interest in this topic. No sedation
      decision is taken without careful consideration. The majority of physicians
      understand the difference between anxiolysis and sedation, most defining the
      latter as using a drug to sedate a patient faced with uncontrollable symptoms.
      All doctors refused to link sedation to euthanasia, although half expressed a
      feeling of causality between sedation and the patient's death - knowing that few
      consider the possibility of transient sedation. The main reluctance among doctors
      is in chronic respiratory insufficiency. Any decision concerning sedation should
      be discussed beforehand with the care team and the resident in charge of the
      patient, but not necessarily with another colleague. There is rarely evidence of
      this discussion in the medical records or of the information given to the patient
      and his family, thus increasing the difficulties of decision-making, especially
      at nights or weekends. The decision to start sedation is seen as difficult
      because it presupposes that a life-threatening short-term prognosis has been
      already been given to the patient. CONCLUSIONS: In this medical population,
      already aware of palliative care issues, the majority of respiratory physicians
      know the definition, the indications for sedation and the principles of
      collective decision, but few are aware of the need of regular reappraisal of the
      sedation, to record it, and of its potential reversibility. There is, therefore,
      a clear need for regular and further training of clinicians to improve their
      professional practice.

PMID- 24461443
TI  - [Chamberlain biopsy is not necessary when mature teratoma is evident on imagery].
AB  - INTRODUCTION: Mature teratoma represents 60 % of germinal cells tumours of the
      mediastinum. Most patients with these tumours are asymptomatic, so the neoplasms
      are usually discovered by accident during routine chest X-ray examination. They
      have specific and almost pathognomonic radiological features. However, patients
      can be symptomatic and may present with chest, back, or shoulder pain; dyspnoea;
      fever; pleural effusion; cough; and bulging of the chest wall. CASE REPORT: We
      report the case of a young woman presenting with a giant mediastinal mature
      teratoma compressing the left lung. The patient was admitted for dyspnoea and non
      productive cough. The chest X-ray showed a mediastinal mass and a chest computed
      tomography scan revealed a heterogeneous pluritissular mass lesion of the
      mediastinum. Complete surgical removal is the treatment of choice for mature
      cystic teratomas, with optimal results and an acceptable surgical risk. This
      approach allows confirmation of the diagnosis and is the only way to rule out the
      presence of malignancy. Surgical biopsy by the Chamberlain method is therefore
      not strictly necessary. DISCUSSION: When chest X-ray and a computed tomography
      scan show specific radiological features of teratoma, a complete resection should
      be undertaken if the patient is fit for surgery. This will confirm the anatomico
      pathological diagnosis, exclude the presence of malignant cells and it represents
      the treatment of choice of mature teratomas.

PMID- 24461444
TI  - [Pseudotumoral pulmonary AL amyloidosis].
AB  - INTRODUCTION: Thoracic involvement in amyloidosis is rare. An isolated
      pseudotumor without extra-thoracic disease suggests a malignant process. We
      present the case of a patient with pseudonodular AL amyloidosis, confirmed by
      lobar lung resection. CASE REPORT: A 57-year-old woman, with a 25-pack-year
      smoking history, presented with a nodular opacity on chest x-ray. Physical
      examination was normal. Thoracic CT-scan revealed an isolated spiculated nodule
      in the right upper lobe. A whole body positron emission tomography (PET) scan
      revealed high FDG activity in this nodule, without evidence of metastatic
      disease. Bronchoscopy was negative. Lobectomy revealed lambda L-chain
      amyloidosis. Investigation for systemic extension was negative. Follow up has
      been unremarkable. CONCLUSION: A spiculated lung nodule on conventional imaging
      (radiography, scanner) is cancer until proven otherwise. The use of PET scan in
      this context is sensitive but not specific. Definitive diagnosis must be obtained
      by histological examination. Nodular lung amyloidosis must be included in the
      differential diagnosis of lung nodules and false-positive FDG PET.

PMID- 24461445
TI  - [Pulmonary nodules and arachnophobia].
AB  - Pulmonary nodules are a common reason for consultation and their investigation
      must always exclude a possible neoplastic cause. This means that, in addition to
      a thorough history, investigations may be necessary which are sometimes invasive
      and therefore potentially a cause of iatrogenic harm. The toxic aetiologies for
      pulmonary nodules are rare. We report a case of a patient with pulmonary nodules
      occurring predominantly in the right lung, about 1cm in diameter, non-cavitating
      without calcification, and sometimes surrounded by a peripheral halo. The nodules
      were a chance finding during preoperative evaluation. After a comprehensive
      review, a reaction to an inhaled irritant was the preferred hypothesis,
      specifically overuse of a compound insecticide containing, in addition to the
      propellant gas and solvent type hydrocarbon - a mixture of piperonyl butoxide, of
      esbiothrine and permethrin. Removal of this led to the complete disappearance of
      nodules. Pathological examination identified bronchiolitis obliterans with
      organising pneumonia accompanied by non-necrotizing granulomas and lipid
      vacuoles.

PMID- 24461440
TI  - [The importance of lung volumes in the investigation of heavy smokers].
AB  - INTRODUCTION: Lung hyperinflation (LH) has become a major concern in the
      management of chronic obstructive pulmonary disease (COPD). MAIN AIM: To evaluate
      the role of lung volumes in the positive diagnosis of COPD and in the assessment
      of airway obstruction reversibility. POPULATION AND METHODS: Three hundred and
      sixty-six male smokers over the age of 35 with more than 40 pack-years exposure
      were included in the study. Plethysmographic data were determined before/after
      taking a bronchodilator (BBD, ABD). Applied definitions: airflow obstruction: BBD
      FEV1/FVC<0.70. LH: BBD residual volume (RV)>upper limit of normal. Expressions of
      reversibility: Deltavariable=(ABD-BBD) values; Deltainit%=Deltavariable/BBD value
      and Deltaref%=Deltavariable/reference value. A 12%init and a 0.2L increase in
      either FEV1 or FVC or a 10%ref or - 300 mL decrease in RV were considered as
      clinically significant. RESULTS: Over the 85 smokers without airflow obstruction,
      68% had LH. In the hyperinflated group (n=314), and compared to changes in FEV1
      and FVC, these RV changes detected more respondents (54% for FEV1 and FVC vs. 65%
      for RV, P=0.002). This was not the case for the group free from LH (n=52) (23%
      for FEV1 and FVC vs. 35% for RV, P=0.09). In the 58 hyperinflated groups free
      from airflow obstruction, and compared to changes in FEV1 and FVC, changes in RV
      detected more respondents (24% for FEV1 and FVC vs. 71% for RV, P=0.0001).
      CONCLUSION: In heavy smokers, it seems essential to include LH as a criterion for
      a positive diagnosis of COPD and of reversibility evaluation.

PMID- 24461446
TI  - [Organizing pneumonia during treatment with mesalazine].
AB  - INTRODUCTION: The distinction between extra-intestinal manifestations of
      ulcerative colitis (UC) and drug-induced pneumonia can often be difficult. CASE
      REPORT: We describe the case of a 72-year-old male who presented fever and sub
      acute respiratory insufficiency, after 4 months of treatment with mesalazine for
      ulcerative colitis (UC). Initial tests found serum C-reactive protein, eosinophil
      count and total IgE to be elevated. Routine bacteriological, fungal and
      mycobacterial cultures were negative. Bronchoalveolar lavage fluid cellularity
      was normal with elevated lymphocyte, neutrophil, and eosinophil counts (35 %
      mononuclear cells, 23 % lymphocytes, 28 % neutrophils, 14 % eosinophils). The
      diagnosis of organizing pneumonia (OP) with eosinophilic pneumonia component was
      confirmed after examination of a lung biopsy specimen. Clinical improvement
      occurred after cessation of mesalazine and initiation of prednisolone
      (1mg/kg/day). Nine months later, a recurrence of gastrointestinal symptoms
      required a 5 months reintroduction of an amino salicylate by topical therapy (4-
      acide aminosalicylique [ASA enemas]). There was no resurgence of the pneumonia.
      DISCUSSION: Organizing pneumonia is a rare extra-intestinal manifestation of UC.
      There was no resurgence of OP after amino salicylate enemas rechallenge but
      mesalazine-induced pneumonia cannot be excluded.

PMID- 24461449
TI  - [Regarding a case of rifampicin-induced pruritus and thrombocytopenia].

PMID- 24461447
TI  - [Telemedicine and lung transplanted patients: A feasibility study].
AB  - BACKGROUND: Lung transplant patients are characterized by a high use of
      healthcare resources and an elevated rate of hospitalization. In lung transplant
      recipients, spirometry home monitoring has been advocated for the early detection
      of acute infection and rejection of the allograft. We will test a new system that
      allows regular monitoring of the patient's pulmonary status at home after
      discharge from hospital. METHODS: This study will be prospective and in addition
      to usual healthcare. The main aim of this feasibility study will be to evaluate
      the compliance of patients in performing three spirometric measurements per week.
      Patients will have received a lung transplant more than three months prior to
      entering the study. The home equipment will comprise a data transmitting box
      (Twitoo((r))) and a spirometer. A decrease of 10% from baseline in one or more
      parameters will generate an alarm, which will lead to the transplant physician
      calling the patient and possibly inviting him to the hospital. EXPECTED RESULTS:
      The feasibility will be considered as acceptable for an average compliance of
      70%. The coefficient of variation and the number of spiro-measurements will be
      adjusted according to the results obtained.

PMID- 24461448
TI  - [Hydatic pulmonary embolism: A very rare complication of renal hydatid cyst].

PMID- 24461450
TI  - [Societe de pneumologie de langue francaise. Guidelines for clinical practice.
      Management of COPD. Update 2012: Pulmonary function tests (Summary)].

PMID- 24461451
TI  - [Individual lung cancer screening in practice. Perspectives on the propositions
      from the multidisciplinary group of the Intergroupe francophone de cancerologie
      thoracique, the Societe d'imagerie thoracique and the Groupe d'oncologie de
      langue francaise].

PMID- 24461452
TI  - On the use of quadrupole mass spectrometric detection for flow modulated
      comprehensive two-dimensional gas chromatography.
AB  - Flow modulated comprehensive two-dimensional gas chromatography with simultaneous
      flame ionization detection (FM GC*GC-FID) and quadrupole mass spectrometric
      detection (FM GC*GC-qMSD) was applied to the analysis of a quantitative reference
      standard sample covering the C5-C14 hydrocarbon range and a kerosene sample. This
      study reports the influence of the data acquisition frequency (DAF) of the qMSD
      on the qualitative and quantitative data. The DAF was varied between 5.27 and
      25.45Hz. In GC*GC-qMSD, the characterization of peaks is getting worse with
      decreasing qMSD frequencies which deteriorate the quality of the 2D contour plots
      of the separations. It is, however, demonstrated that the improved
      characterization of the peaks at high qMSD frequencies is combined with loss in
      sensitivity and in spectral quality. Dependences of a (2)D hydrocarbon peak area
      (?Ai of all corresponding (2)D peaks) on the DAFs show negative slopes which
      testify the conclusion that the sensitivity of GC*GC-qMSD determinations
      decreases with the increase of DAF. Consequently, the limits of detection (LOD)
      and quantification (LOQ) increase with the increase of DAF. Moreover, quality
      criteria on recorded spectral data also indicate that the lower the DAF is, the
      higher is the spectral quality. 

PMID- 24461454
TI  - Outcomes from out of hospital cardiac arrest (OHCA)? What really matters is the
      patient.

PMID- 24461455
TI  - Alphaproteobacteria species as a source and target of lateral sequence transfers.
AB  - Alphaproteobacterial genomes show a remarkable genome plasticity linked with
      different lifestyles (intracellular, facultative, and free-living). They
      represent the major source of the genome repertoire of mitochondria, and their
      genes (specifically those of Wolbachia) have been massively transferred into
      their modern eukaryotic hosts, such as arthropods and nematodes. Conversely,
      other organisms (bacteria, viruses, archaea, and eukaryotes) and selfish DNA have
      contributed to their genomes. This bidirectional lateral sequence transfer
      explains the mosaic nature of their genomes. In contrast to those living in
      allopatry, alphaproteobacteria living in sympatry (in protist cells such as in
      the environment) favor lateral sequence transfer. Evidence shows that
      intracellular transfer of the type IV secretion system might have played a
      critical role in the evolution of these alphaproteobacteria. 

PMID- 24461453
TI  - Staphylococcus aureus: the multi headed hydra resists and controls human
      complement response in multiple ways.
AB  - The Gram positive human pathogen Staphylococcus aureus causes a spectrum of human
      diseases including pneumonia, tissue and skin infections, endocarditis, pneumonia
      and sepsis. The increasing number of resistant bacteria and the threat of
      methicillin resistant S. aureus (MRSA) urge for the need to develop new
      antibacterial compounds. A prerequisite for development of such anti microbial
      compounds is a better understanding of the complex immune crosstalk between the
      pathogenic bacterium and its human host. To this end proteins staphylococcal
      proteins that contribute to innate immune evasion especially to complement
      control need to be identified and their mode of action needs to be analyzed in
      order to provide new targets for immune interference. 

PMID- 24461463
TI  - The challenge to patient safety by emerging Gram negative pathogens.

PMID- 24461460
TI  - What we (don't) know about what we know.
AB  - The hypothesis of unconscious influences on complex behavior is observationally
      equivalent to the dissociability of cognition and metacognition (reportability).
      The target article convincingly argues that evidence for unconscious influence is
      limited by the quality of the metacognitive measure used. However, it understates
      the empirical evidence for unconscious influences and overlooks considerations of
      cognitive architecture that make cognitive/metacognitive dissociations likely. 

PMID- 24461456
TI  - Aldehyde dehydrogenase 1 expression in inflammatory breast cancer as measured by
      immunohistochemical staining.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive type of
      breast carcinoma. Despite multimodality approaches, the clinical outcome of
      patients with IBC remains poor. Tumors arising from cancer stem cells (CSCs) are
      associated with drug resistance, tumor recurrence, and poor prognosis. This study
      aimed to evaluate expression of aldehyde dehydrogenase 1 (ALDH1), a putative stem
      cell marker, in IBC tumors. MATERIALS AND METHODS: Tissue microarrays of 74
      surgically resected IBC tumors were immunohistochemically stained for ALDH1. The
      results were correlated with clinicopathologic parameters and survival data and
      were compared with findings published in the literature. RESULTS: The median
      follow-up time of the cohort was 42.1 months, and the 5-year overall survival
      (OS) rate was 46%. Twenty-four tumors (32%) were positive for ALDH1 staining.
      However, ALDH1 expression was not significantly associated with clinicopathologic
      variables, including lymph node status, tumor grade, and the status of estrogen
      receptor, progesterone receptor, and human epidermal growth factor receptor 2.
      Log-rank testing found that ALDH1 expression was not significantly associated
      with the OS rate, although there was a trend toward an association with lower OS
      rate (P = .07). The findings were consistent with some of the published data, but
      substantial inconsistency among reports was noted. CONCLUSION: In this IBC
      cohort, no significant correlation between ALDH1 expression and prognosis or
      other clinicopathologic variables was found. Although sample size and selection
      criteria may be contributory factors, inconsistent results reported in the
      literature raise concern regarding the reliability of immunohistochemically
      identified ALDH1 as a sole marker of breast CSCs. Further study is required to
      elucidate the significance of CSCs in IBC biology.

PMID- 24461461
TI  - Impact of 13-valent pneumococcal conjugate vaccine on otitis media bacteriology.
AB  - OBJECTIVES: To determine the microbiology of otitis media (OM) since the
      introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in February
      2010. METHODS: Middle ear effusion from a pediatric Otolaryngology population
      undergoing pressure equalization tube (PET) placement was obtained and sent for
      aerobic culture and antibiotic susceptibility testing between August 2012 and
      April 2013. Vaccination records were obtained and statistical analysis was
      completed. RESULTS: During the 8-month period, 236 ears were evaluated, and of
      those 39 ears were found to have positive cultures. The single nonvaccine
      Streptococcus pneumoniae (serotype 16) isolate was obtained from a PCV7-only
      vaccinated patient and was penicillin susceptible. The three most common isolates
      were Staphylococcus coagulase negative (57%), Haemophilus influenzae (17%), and
      Moraxella catarrhalis (7%). CONCLUSIONS: This study is the first to assess the
      bacteriology of OM in a pediatric population undergoing PET placement in the
      immediate post-PCV13 era. Our study is limited by sample size; however, the lack
      of S. pneumoniae cultures indicates that PCV13 has had a significant impact on
      pneumococcal infections during these initial years following licensure.

PMID- 24461457
TI  - 72-gene classifier for predicting prognosis of estrogen receptor-positive and
      node-negative breast cancer patients using formalin-fixed, paraffin-embedded
      tumor tissues.
AB  - BACKGROUND: The 95-gene classifier (95-GC) can classify patients with estrogen
      receptor (ER)-positive and node-negative breast cancer into those with low and
      high risk of relapse with an accuracy similar to that of 21-GC (Oncotype DX).
      Because 95-GC uses RNA from fresh-frozen (FF) tumor tissues, we herein attempted
      to develop a gene classifier that is applicable to RNA from formalin-fixed
      paraffin-embedded (FFPE) tumor tissues. PATIENTS AND METHODS: 25 paired FF and
      FFPE tumor tissues were subjected to DNA microarray for gene-expression analysis.
      Of the 95 probes included in the 95-GC, 72 were selected for construction of the
      gene classifier for FFPE tumor tissues, because the gene expression detected by
      these 72 probes was well preserved in the FFPE tumor tissues. RESULTS: The 72-GC
      was constructed with these 72 probes for the training set comprising 549 FF tumor
      tissues and validated with 434 FF tumor tissues (relapse-free survival at 10
      years was 91% for the low-risk and 74% for the high-risk group (P = 3.74 * 10(
      7)). The predictive capability of 72-GC for prognosis was found to be comparable
      to that of 95-GC. The 25 paired FF and FFPE tumor tissues from each of 25
      patients were classified into the same risk group by 72-GC for 23 patients (92%
      concordance). 72-GC using the FFPE tumor tissues showed that the prognosis for
      the low-risk group was significantly (P = .007) better than for the high-risk
      group. CONCLUSION: 72-GC is comparable to 95-GC in terms of accuracy of prognosis
      prediction, and may be effective for FFPE tumor tissues.

PMID- 24461459
TI  - Assessing breast cancer risk models in Marin County, a population with high rates
      of delayed childbirth.
AB  - INTRODUCTION: This study was designed to compare the Breast Cancer Risk
      Assessment Tool (BCRAT; Gail), International Breast Intervention Study (IBIS;
      Tyrer-Cuzick), and BRCAPRO breast cancer risk assessment models using data from
      the Marin Women's Study, a cohort of women within Marin County, California, with
      high rates of breast cancer, nulliparity, and delayed childbirth. Existing models
      have not been well-validated in these high-risk populations. METHODS:
      Discrimination was assessed using the area under the receiver operating
      characteristic curve (AUC) and calibration by estimating the ratio of expected-to
      observed (E/O) cases. The models were assessed using data from 12,843
      participants, of whom 203 had developed cancer during a 5-year period. All tests
      of statistical significance were 2-sided. RESULTS: The IBIS model achieved an AUC
      of 0.65 (95% confidence interval [CI], 0.61-0.68) compared with 0.62 (95% CI,
      0.59-0.66) for BCRAT and 0.60 (95% CI, 0.56-0.63) for BRCAPRO. The corresponding
      estimated E/O ratios for the models were 1.08 (95% CI, 0.95-1.25), 0.81 (95% CI,
      0.71-0.93), and 0.59 (95% CI, 0.52-0.68). In women with age at first birth > 30
      years, the AUC for the IBIS, BCRAT, and BRCAPRO models was 0.69 (95% CI, 0.62
      0.75), 0.63 (95% CI, 0.56-0.70), and 0.62 (95% CI, 0.56-0.68) and the E/O ratio
      was 1.15 (95% CI, 0.89-1.47), 0.81 (95% CI, 0.63-1.05), and 0.53 (95% CI, 0.41
      0.68), respectively. CONCLUSIONS: The IBIS model was well calibrated for the high
      risk Marin mammography population and demonstrated the best calibration of the 3
      models in nulliparous women. The IBIS model also achieved the greatest overall
      discrimination and displayed superior discrimination for women with age at first
      birth > 30 years.

PMID- 24461458
TI  - Effect of age and race on quality of life in young breast cancer survivors.
AB  - BACKGROUND: Given their early age at diagnosis, young breast cancer survivors
      (YBCSs) face issues that differ widely from their older counterparts. PATIENTS
      AND METHODS: We mailed a survey to 2209 patients who were <= 45 years at the time
      of breast cancer (BC) diagnosis. Each survey was composed of the Quality of Life
      in Adult Cancer Survivors instrument, Menopause Symptom Scale, and questions
      aimed at obtaining pertinent background information. RESULTS: One thousand ninety
      patients completed the survey. Mean age at time of diagnosis was 39.5 years;
      median years from diagnosis was 6.6 years. Distress related to vaginal dryness (P
      = .0002) and pain from intercourse (P = .0014) was significantly higher in
      patients who were < 5 years from diagnosis compared with those > 10 years from
      diagnosis. In the area of financial problems, black women had greater distress
      than did white women (P = .0010). Compared with white women, Hispanic women had
      worse family distress scores (P = .0028) and summary cancer-specific scores (P =
      .0076). Patients > 10 years from diagnosis had less sexual interest (P = .003)
      than did women who were closer to diagnosis. Women >= 40 years at diagnosis had
      significantly lower sexual interest (P = .0016) than did women < 40 years. Stage
      and neoadjuvant chemotherapy did not have a significant effect on quality of life
      (QOL). CONCLUSION: Even in comparison to stage and neoadjuvant chemotherapy,
      race, age at diagnosis, and time from diagnosis have significant long-term
      effects on QOL after treatment for BC.

PMID- 24461464
TI  - Efficacy of continuous wound infiltration of local anesthetic for pain relief
      after gynecologic laparoscopy.
AB  - OBJECTIVE: To assess the efficacy of analgesia provided by continuous ropivacaine
      wound infiltration after gynecologic laparoscopy. METHODS: Sixty patients who
      underwent gynecologic laparoscopy at Ajou University School of Medicine, Suwon,
      Republic of Korea, between March and May 2012 were randomized to receive either
      intravenous fentanyl and ketorolac infusion on demand by patient-controlled
      analgesia (IV PCA group, n=31) or continuous wound infiltration of local
      ropivacaine (CWI group, n=29). Postoperative pain and postoperative nausea and
      vomiting (PONV) were assessed via a visual analog scale. The number of patients
      who requested rescue analgesia was recorded. RESULTS: There was no significant
      difference in postoperative pain between the 2 groups, but more patients
      requested rescue analgesia in the CWI group than in the IV PCA group in 24 hours
      (18 versus 9 patients, respectively; P=0.010). The PONV scores at 12 and 24 hours
      were, respectively, 0.28 and 0.27 in the CWI group, and 0.71 and 0.73 in the IV
      PCA group (P=0.004). Nine patients requested cessation of IV PCA because of
      severe nausea or vomiting. CONCLUSION: Continuous ropivacaine wound infiltration
      was found to be as effective as patient-controlled analgesia for postoperative
      pain relief after gynecologic laparoscopy. This technique provides good analgesia
      with less opioid analgesic requirement and few adverse effects.

PMID- 24461467
TI  - [Transvaginal hydrolaparoscopy for infertility investigation: a retrospective
      study, about 262 patients].
AB  - OBJECTIVES: To evaluate fertiloscopy's results and to redefine its place in the
      management of female infertility. PATIENTS AND METHODS: Retrospective study
      including 262 cases of fertiloscopy and 260 patients with primary or secondary
      idiopathic infertility. Analysis of infertility assessment's findings
      (hysterosalpingography), perioperative data (operating technique, laparoscopic
      conversion, failures and complications). Comparison of hysterosalpingography's
      findings and peroperative data; comparison of fertiloscopy and laparoscopy's
      findings. RESULTS: Access to peritoneal cavity was possible for 248
      fertiloscopies (95%), and pelvic exploration was considered as complete for 226
      cases (86%). Laparoscopic conversion was necessary in 54 cases (21%) and
      indicated by surgical pathology in more of one third of the cases (n=20). Our
      failure rate was only 5,3% (n=14), partially thanks to posterior colpotomie (70%
      of failures avoided). We deplored 8 complications (3.05%) which were not severe
      (no bowel injury), among which half were linked with the hysteroscopy (uterus
      perforation). In the cases of laparoscopic conversion, laparoscopic findings
      confirmed per-fertiloscopic data, considering adhesions and tubal patency.
      Hysterosalpingography had poor sensibility and positive predictive value.
      DISCUSSION AND CONCLUSION: Fertiloscopy is a safe, reproducible and not much
      invasive procedure. It can be substituted to laparoscopy in infertility
      assessment when there is no obvious surgical indication. Moreover, it could be
      considered as a first line way of investigation in female infertility management,
      instead of hysterosalpingography which has poor sensibility and positive
      predictive value.

PMID- 24461465
TI  - Longitudinal health outcome and wellbeing of mother-infant pairs after adolescent
      pregnancy in Reunion Island, Indian Ocean.
AB  - OBJECTIVE: To evaluate longitudinal care needs and health service access among
      mother-infant pairs after adolescent pregnancy. METHODS: In a case-control study,
      data were analyzed from primiparous adolescent and adult mother-infant pairs who
      delivered at Reunion Island University Hospital, France, between January 2004 and
      December 2006, and were followed-up from maternity discharge until December 2011.
      Infant outcomes were hospitalization during the first 2 years of life, hospital
      access for "non-medical" reasons, and neuropsychiatric care. Maternal outcomes
      were number of pregnancies and childbirths, rapid repeat pregnancy (RRP) rate,
      pregnancy morbidities, and use of health services. RESULTS: Data from 476 cases
      and 476 controls were analyzed. Adolescent and control offspring did not differ
      in the measured outcomes. Adolescent and control mothers had, respectively, 2.4
      +/- 1.3 and 1.9 +/- 1.1 pregnancies; 1.9 +/- 0.8 and 1.6 +/- 0.7 childbirths; and
      RRP rates of 7.6% and 2.7% (all P<0.001). Adolescents had less pregnancy-related
      pathologies at the index pregnancy and more frequently had natural deliveries
      (P<0.05). Younger mothers exhibited higher rates (19.7% versus 6.9%, P=0.001) of
      care for psychosocial reasons (suicide attempt, acute alcohol or drug
      intoxication, road accident, psychiatric problems, physical abuse). CONCLUSION:
      Concerns arise from the long-term psychosocial risk among adolescent mothers.

PMID- 24461474
TI  - Unconscious influences on decision making: neuroimaging and neuroevolutionary
      perspectives.
AB  - Newell and Shanks provide a useful critique on unconscious decision making.
      However, they do not consider an important set of functional brain imaging
      studies of unconscious processes. Here we review briefly the relevant brain
      imaging and psychobiological literature and its implications for understanding
      unconscious decision making. 

PMID- 24461469
TI  - OHVIRA syndrome presenting with acute abdomen: a case report and review of the
      literature.
AB  - Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis
      (OHVIRA) or Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital
      urogenital anomaly. A 13-year-old female presented with acute abdominal pain and
      dysmenorrhea. Ultrasonography and magnetic resonance imaging showed uterus
      didelphys, hematometrocolpos, obstructed hemivagina, and right renal agenesis.
      Hemivaginal septal resection and anastomosis between the obstructed hemivagina
      and the normal vagina was tried, but it was not possible. Unilateral hysterectomy
      was performed. HWW syndrome may present with acute abdomen and is usually treated
      with vaginal septum resection and drainage of the hematometrocolpos. 

PMID- 24461471
TI  - Unilocular macrocystic serous cystadenoma of the pancreas--atypical features: a
      case report.
AB  - The authors report and discuss an exceedingly rare case of a unilocular
      macrocystic serous cystadenomas diagnosed in a 63-year-old female patient, which
      was preoperatively misdiagnosed as a mucinous cystic neoplasm, due to the
      atypical magnetic resonance (MR) imaging features shown at presentation and the
      misleading results obtained through cystic fluid analysis. This manuscript
      overviews the typical and atypical manifestations of this entity and highlights
      the advantages, potential limitations and pitfalls of both MR imaging and cystic
      fluid analysis. 

PMID- 24461470
TI  - Right nutcracker syndrome associated with left-sided inferior vena cava,
      hemiazygos continuation and persistant left superior vena cava: a rare
      combination.
AB  - The term nutcracker syndrome refers to compression of left renal vein between
      aorta and superior mesenteric artery causing renal venous hypertension. Right
      nutcracker syndrome associated with a left-sided inferior vena cava is an
      extremely rare anomaly. Reported two cases in English literature were diagnosed
      by ultrasonography and computed tomography angiography in adulthood. Herein, we
      present a case of right nutcracker syndrome with left-sided inferior vena cava
      and hemiazygos continuation in a 12-year-old girl. 

PMID- 24461462
TI  - Crystal structures of the phosphorylated BRI1 kinase domain and implications for
      brassinosteroid signal initiation.
AB  - Brassinosteroids, which control plant growth and development, are sensed by the
      membrane receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Brassinosteroid
      binding to the BRI1 leucine-rich repeat (LRR) domain induces heteromerisation
      with a SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK)-family co-receptor. This
      process allows the cytoplasmic kinase domains of BRI1 and SERK to interact, trans
      phosphorylate and activate each other. Here we report crystal structures of the
      BRI1 kinase domain in its activated form and in complex with nucleotides. BRI1
      has structural features reminiscent of both serine/threonine and tyrosine
      kinases, providing insight into the evolution of dual-specificity kinases in
      plants. Phosphorylation of Thr1039, Ser1042 and Ser1044 causes formation of a
      catalytically competent activation loop. Mapping previously identified
      serine/threonine and tyrosine phosphorylation sites onto the structure, we
      analyse their contribution to brassinosteroid signaling. The location of known
      genetic missense alleles provide detailed insight into the BRI1 kinase mechanism,
      while our analyses are inconsistent with a previously reported guanylate cyclase
      activity. We identify a protein interaction surface on the C-terminal lobe of the
      kinase and demonstrate that the isolated BRI1, SERK2 and SERK3 cytoplasmic
      segments form homodimers in solution and have a weak tendency to heteromerise. We
      propose a model in which heterodimerisation of the BRI1 and SERK ectodomains
      brings their cytoplasmic kinase domains in a catalytically competent arrangement,
      an interaction that can be modulated by the BRI1 inhibitor protein BKI1. 

PMID- 24461473
TI  - Folic acid supplementation with and without vitamin B6 and revascularization
      risk: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND & AIMS: There is a growing amount of data and a continuing controversy
      over the effect of folic acid supplementation with and without vitamin B6 on
      revascularization risk. METHODS: We conducted a meta-analysis based on up-to-date
      published relevant randomized trials to further examine this issue. Relative risk
      (RR) was used to measure the effect of folic acid supplementation on risk of
      revascularization using a random-effects model. Total revascularization was
      defined as any arterial revascularization. Restenosis was defined as stenosis of
      more than 50 percent of the luminal diameter. RESULTS: Overall, folic acid
      supplementation had no significant effect on coronary revascularization (9
      trials, n = 27,418, RR = 0.99; 95%CI:0.88-1.11, P = 0.88), coronary artery bypass
      grafting (CABG) (5 trials, n = 10,703, 0.90; 0.79-1.03, P = 0.11), percutaneous
      coronary intervention (PCI) (5 trials, n = 10,703, 1.05; 0.89-1.23, P = 0.59),
      coronary restenosis (3 trials, n = 926, 1.05; 0.89-1.23, P = 0.59) or total
      revascularization (7 trials, n = 29,314, 1.06; 95%CI: 0.99-1.13, P = 0.10).
      However, a greater beneficial effect was observed for coronary revascularization
      among those trials with a moderate dose of vitamin B6 (5-10 mg/d; RR: 0.47;
      95%CI: 0.28-0.80, P = 0.005), but not in trials without vitamin B6 or with a high
      dose of vitamin B6. And a non-significant greater total revascularization risk
      was observed in trials with a higher folic acid dose (>2 mg/d, RR = 1.11; 95%CI:
      0.98-1.25, P = 0.09; >=5 mg/d, RR = 1.98; 95%CI: 0.93-4.20, P = 0.08).
      CONCLUSIONS: Our analyses indicate that folic acid supplementation has no
      significant effect on coronary revascularization, CABG, PCI, coronary restenosis
      or total revascularization. However, a combination of folic acid and moderate
      vitamin B6 may be beneficial in reducing coronary revascularization risk.

PMID- 24461477
TI  - Fundamental frequency changes of Persian speakers across the life span.
AB  - This study was designed to investigate changes in fundamental frequency (F0)
      across the life span in Persian speakers. Four hundred children and adults were
      asked to produce a sustained phonation of vowel /a/ and their voice samples were
      studied in 10 age groups. F0 was analyzed using the software Praat (Version
      5.1.17.). The results revealed that (1) the mean F0 in both sexes decreases from
      childhood to adulthood; (2) significant F0 differences between boys and girls
      begin at the age of 12 years; and (3) the range of F0 changes in the life span is
      greater in men (178.38 Hz) than in women (113.57 Hz). These findings provide new
      data for Persian-speaking children, women, and men and could be beneficial for
      Iranian speech and language pathologists.

PMID- 24461468
TI  - Pineal gland involvement in Erdheim-Chester disease detected on (18)F-FDG PET-CT
      imaging: a case report and review of literature.
AB  - Erdheim-Chester disease (ECD) is a rare non-Langerhan's cell histiocytosis
      affecting multiple organ systems. The most common systemic manifestations are
      bone lesions, infiltration of the pituitary stalk sometimes leading to diabetes
      insipidus, pulmonary fibrosis, cardiac failure and exophthalmus. Neurological
      symptoms as the first clinical manifestations of ECD have been reported in less
      than one third of cases. We report a rare presentation of a patient of ECD on 18F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography
      which revealed abnormal (18)F-FDG accumulation in the region of pineal gland,
      pericardium and bilateral distal tibiae. 

PMID- 24461472
TI  - Disease associated malnutrition correlates with length of hospital stay in
      children.
AB  - BACKGROUND & AIMS: Previous studies reported a wide range of estimated
      malnutrition prevalence (6-30%) in paediatric inpatients based on various
      anthropometric criteria. We performed anthropometry in hospitalised children and
      assessed the relationship between malnutrition and length of hospital stay (LOS)
      and complication rates. METHODS: In a prospective multi-centre European study,
      2567 patients aged 1 month to 18 years were assessed in 14 centres in 12
      countries by standardised anthropometry within the first 24 h after admission.
      Body mass index (BMI) and height/length <-2 standard deviation scores (SDS, WHO
      reference) were related to LOS (primary outcome), frequency of gastrointestinal
      (diarrhoea and vomiting) and infectious complications (antibiotic use), weight
      change during stay (secondary outcomes) and quality of life. RESULTS: A BMI <-2
      SDS was present in 7.0% of the patients at hospital admission (range 4.0-9.3%
      across countries) with a higher prevalence in infants (10.8%) and toddlers aged 1
      2 years (8.3%). A BMI <-2 to >=-3 SDS (moderate malnutrition) and a BMI <-3 SDS
      (severe malnutrition) was associated with a 1.3 (CI95: 1.01, 1.55) and 1.6 (CI95:
      1.27, 2.10) days longer LOS, respectively (p = 0.04 and p < 0.001). Reduced BMI <
      2 SDS was also associated to lower quality of life, and more frequent occurrence
      of diarrhoea (22% vs 12%, p < 0.001) and vomiting (26% vs 14%, p < 0.001).
      CONCLUSION: Disease associated malnutrition in hospitalised children in Europe is
      common and is associated with significantly prolonged LOS and increased
      complications, with possible major cost implications, and reduced quality of
      life. This study was registered at clinicaltrials.gov as NCT01132742.

PMID- 24461479
TI  - Trends in microbial proteomics.

PMID- 24461475
TI  - Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related
      sequence A (MICA) shedding in renal cell carcinoma.
AB  - INTRODUCTION: The MHC class i chain-related molecule A (MICA) is a ligand for the
      natural killer group 2, member D (NKG2D) immunoreceptor activation. The
      engagement of tumor cell surface MICA to NKG2D stimulates the NK and T cell
      antitumor immunity. Shedding of MICA by tumor cells facilitates tumor immune
      evasion, which might partially contribute to tumor progression. MATERIAL AND
      METHODS: Inmunohistochemistry was performed on both normal and neoplastic renal
      tissue. Human renal carcinoma cell lines 786-0 and ACHIN were transfected and
      target sequences to silence human MMP2 by shRNA expression were established. The
      degree of MICA shedding was measured and quantitative real-time PCR and Western
      blot analysis were performed. RESULTS: The membrane type matrix metalloproteinase
      2 (MMP2) mediated the MICA shedding, which was blocked by suppression of MMP2
      expression. Concomitantly, MMP2 over-expression enhanced the MICA shedding,
      indicating that MMP2 was involved in the renal cell carcinoma-associated
      proteolytic release of soluble MICA (sMICA), which facilitated the tumor immune
      escape. CONCLUSIONS: These findings suggested that MMP2 might be a new potential
      target for tumor immune therapy. Elucidation of the mechanisms by which tumors
      shed MICA could be of a great importance for cancer treatment in order to
      reinforce the NK and T cell antitumor immunity.

PMID- 24461466
TI  - Pattern of microbial translocation in patients living with HIV-1 from Vietnam,
      Ethiopia and Sweden.
AB  - INTRODUCTION: The role of microbial translocation (MT) in HIV patients living
      with HIV from low- and middle-income countries (LMICs) is not fully known. The
      aim of this study is to investigate and compare the patterns of MT in patients
      from Vietnam, Ethiopia and Sweden. METHODS: Cross-sectional samples were obtained
      from treatment-naive patients living with HIV-1 and healthy controls from Vietnam
      (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal
      samples were obtained from a subset of the Vietnamese (n=24) in whom
      antiretroviral therapy (ART) and tuberculostatics were given. Plasma
      lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the
      endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent
      assay. RESULTS: All three biomarkers were significantly increased in patients
      living with HIV-1 from all countries as compared to controls. No differences were
      found between males and females. Vietnamese and Ethiopian patients had
      significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes.
      ART reduced these levels for the Vietnamese. Vietnamese patients given
      tuberculostatics at initiation of ART had significantly lower levels of anti
      flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did
      not develop opportunistic infection. CONCLUSIONS: Higher MT is common in patients
      living with HIV compared to healthy individuals, and in patients from LMICs
      compared to patients from a high-income country. Treatment with tuberculostatics
      decreased MT while higher levels of MT are associated with a poorer clinical
      outcome.

PMID- 24461476
TI  - The diversion and injection of a buprenorphine-naloxone soluble film formulation.
AB  - BACKGROUND: We compared the diversion and injection of a new formulation of
      buprenorphine, a buprenorphine-naloxone film product (BNX film), with
      buprenorphine-naloxone tablets (BNX tablets), mono-buprenorphine (BPN) and
      methadone (MET) in Australia. METHODS: Surveys were conducted with people who
      inject drugs regularly (PWID) (2004-2012) and opioid substitution treatment (OST)
      clients (2012, N=543). Key outcome measures: the unsanctioned removal of
      supervised doses, diversion, injection, motivations, drug liking and street
      price. Levels of injection among PWID were adjusted for background availability
      of medication using sales data. Doses not taken as directed by OST clients were
      adjusted by total number of daily doses dispensed. RESULTS: Among out-of
      treatment PWID, levels of injection for BNX film were comparable to those for MET
      and BNX tablet formulations, adjusting for background availability; BPN injecting
      levels were higher. Among OST clients, recent injecting of one's medication was
      similar among clients in all OST types; weekly or more frequent injection of
      prescribed doses was reported by fewer BNX film clients (3%; 95% CI: 1-6) than
      BPN clients (11%; 95% CI: 3-17), but at levels similar to those observed among
      MET and BNX tablet clients. The proportion of BNX film doses injected was lower
      than that for BPN and BNX tablets, and equivalent to that for MET. The majority
      of BNX film doses injected by OST clients were unsupervised doses, although some
      injection of supervised doses of BNX film did occur. The median price of all
      buprenorphine forms on the illicit market was the same. CONCLUSIONS: Non
      adherence and diversion of the BNX film formulation was similar to MET and BNX
      tablet formulations; BPN had higher levels of all indicators of non-adherence and
      diversion.

PMID- 24461478
TI  - Medical factors associated with early IVF discontinuation.
AB  - Even when IVF is reimbursed by the social insurance system, as in France, high
      discontinuation rates have been reported and some patients drop out as soon as
      the first failed IVF cycle. This study aims to investigate medical factors
      associated with treatment discontinuation in an IVF centre after the first
      unsuccessful cycle. The study included 5135 couples recruited in eight French IVF
      centres and who had had an unsuccessful first IVF cycle in these centres in 2000
      2002 (i.e. no live birth). Of these couples with a first failed IVF, 1337 did not
      have a second IVF in the centre (26%, 'early discontinuation group') and 3798
      continued treatment with a second IVF in the centre. The characteristics of
      couples who discontinued IVF treatment were compared with those who continued
      using logistic regressions. Older women, women with duration of infertility
      >5years, with female factor or unexplained infertility, with 0 or 1 oocyte
      retrieved and no embryo transfer during the first IVF were more likely to
      discontinue treatment early. Risk of early discontinuation was associated with
      medical factors that are also well known to be associated with impaired chance of
      successful IVF. Even when IVF is reimbursed by the social insurance system, as in
      France, high discontinuation rates have been reported and some patients drop out
      as soon as the first failed IVF cycle. This study aims to investigate medical
      factors associated with treatment discontinuation in an IVF centre after the
      first unsuccessful cycle. The study included 5135 couples recruited in eight
      French IVF centres who had had an unsuccessful first IVF cycle in these centres
      in 2000-2002 (i.e. who remained childless after a first cycle). Of these couples
      with a first failed IVF, 1337 did not have a second IVF in the centre and 3798
      continued treatment with a second IVF in the centre. The characteristics of
      couples who discontinued IVF treatment were compared with those who continued.
      After a first failed IVF cycle, more than one-quarter (26%) of couples
      discontinued IVF treatment. Older women, women with duration of infertility
      >5years, with female factor or unexplained infertility, with 0 or 1 oocyte
      retrieved and with no embryo transfer during the first IVF were more likely to
      discontinue treatment early. The risk of early discontinuation was associated
      with medical factors that are also well known to be associated with impaired
      chance of success during IVF treatment. A next step would be to examine whether
      the early discontinuation results from a decision of the couple themselves, from
      medical, psychological and/or social staff counselling or from some combination
      of all of these factors. 

PMID- 24461480
TI  - Extremely rigorous subliminal paradigms demonstrate unconscious influences on
      simple decisions.
AB  - While showing unconscious influences on complex decisions is indeed difficult,
      relevant awareness in relatively simpler subliminal paradigms is more easily
      assessed. Utilizing objective detection (vs. more typical identification or
      classification) tasks to assess awareness overcomes longstanding residual
      methodological problems, and prior work using such methods (e.g., Snodgrass &
      Shevrin 2006) clearly shows unconscious influences on simple decisions. 

PMID- 24461481
TI  - Incremental prognostic value of multiparametric echocardiographic assessment for
      severe aortic stenosis.

PMID- 24461483
TI  - PNPLA3 I148M variant as a risk factor for carotid atherosclerosis in chronic
      hepatitis C.

PMID- 24461482
TI  - Cardiac magnetic resonance in myocarditis from adult onset Still's disease
      successfully treated with anakinra.

PMID- 24461484
TI  - Iatrogenic renal artery stenosis after renal sympathetic denervation.

PMID- 24461485
TI  - Cardiovascular health and caffeine consumption. A population-based study in rural
      Ecuador.

PMID- 24461486
TI  - Galen, father of systematic medicine. An essay on the evolution of modern
      medicine and cardiology.
AB  - Galen (129-217) was the ultimate authority on all medical subjects for 15
      centuries. His anatomical/physiological concepts remained unchallenged until well
      into the 17th century. He wrote over 600 treatises, of which less than one-third
      exist today. The Galenic corpus is stupendous in magnitude; the index of word
      entries in it contains 1300 pages. Galen's errors attracted later attention, but
      we should balance the merits and faults in his work because both exerted profound
      influences on the advancement of medicine and cardiology. Galen admonished us to
      embrace truth as identified by experiment, warning that everyone's writings must
      be corroborated by directly interrogating Nature. His experimental methods'
      mastery is demonstrated in his researches, spanning every specialty. In his life
      sustaining schema, the venous, arterial, and nervous systems, with the liver,
      heart, and brain as their respective centers, were separate, each distributing
      through the body one of three pneumata: respectively, the natural, the vital, and
      the animal spirits. He saw blood carried both within the venous and arterial
      systems, which communicated by invisible "anastomoses," but circulation eluded
      him. The "divine Galen's" writings, however, contributed to Harvey's singular
      ability to see mechanisms completely differently than other researchers, thinkers
      and experimentalists. Galen was the first physician to use the pulse as a sign of
      illness. Some representative study areas included embryology, neurology, myology,
      respiration, reproductive medicine, and urology. He improved the science and use
      of drugs in therapeutics. Besides his astounding reputation as scientist-author
      and philosopher, Galen was deemed a highly ethical clinician and brilliant
      diagnostician.

PMID- 24461489
TI  - Tissue factor pathway inhibitor is an early biomarker of myocardial injury in
      patients with ST-segment elevation acute myocardial infarction.

PMID- 24461495
TI  - Age-related macular degeneration and cataract surgery.

PMID- 24461490
TI  - Subclinical systolic dysfunction in left ventricular non-compaction
      cardiomyopathy unmasked by contrast echocardiography.

PMID- 24461487
TI  - Does a chronic inflammatory state have a role in the development of mitral
      restenosis after balloon mitral valvuloplasty?

PMID- 24461488
TI  - When will the most important confounder of percentage flow-mediated dilation be
      reported and adjusted for at the study level?

PMID- 24461491
TI  - Reversible posterior leukoencephalopathy syndrome during regorafenib treatment: a
      case report and literature review of reversible posterior leukoencephalopathy
      syndrome associated with multikinase inhibitors.

PMID- 24461496
TI  - Simulation of neodymium:YAG posterior capsulotomy for ophthalmologists in
      training.
AB  - We describe a new method for training ophthalmologists to perform a neodymium:YAG
      (Nd:YAG) posterior capsulotomy. Our model consists of an artificial anterior
      chamber that can be adjusted to fit any laser instrument and houses an
      intraocular lens (IOL). The posterior surface of the IOL is coated with a crust
      simulating posterior capsule opacification (PCO). This model PCO reacts similarly
      to real PCO when the Nd:YAG laser is applied to it. It creates conditions
      simulating near-real posterior capsulotomy and has been used successfully to
      train 3 novice residents who had not performed the procedure. The model is
      simple, reusable, and inexpensive. We believe it may be a valuable tool in
      training ophthalmologists to perform an Nd:YAG posterior capsulotomy. FINANCIAL
      DISCLOSURE: Neither author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 24461497
TI  - Using catheter needles to deliver an intraocular lens for intrascleral fixation.
AB  - A new method for delivering intraocular lens (IOL) haptics through sclerotomies
      for intrascleral fixation using catheter needles was evaluated in pig eyes. A
      bent catheter needle was used to penetrate the surgical corneal wound from the
      presumed sclerotomy. Extraocularly, the leading haptic of the IOL was fixated
      between the external tube and the internal needle of the catheter needle. The
      fixation was strong enough to support the IOL and to extract the leading haptic
      through the sclerotomy site. The trailing haptic was fixated using another
      catheter needle extraocularly and was subsequently delivered through another
      sclerotomy site. Guiding with a needle was the only intraocular manipulation when
      delivering the trailing haptic and catheter needle through the sclerotomy. This
      new method is easy and safe and does not require special devices compared with
      other methods. Clinical evaluation in human eyes should be performed. FINANCIAL
      DISCLOSURE: Dr. Akimoto is a consultant to Kowa Co. Ltd. A patent application on
      the modified catheter needle is planned. No other author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24461492
TI  - Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce
      toxicity in early- or late-stage colorectal cancer patients treated with
      infusional 5-fluorouracil-based chemotherapy regimens.
AB  - INTRODUCTION: Therapeutic plasma 5-fluorouracil (5-FU) levels are achieved in
      only 20% to 30% of patients with the current practice of administering 5-FU doses
      based on body surface area (BSA). Alternatively, 5-FU doses can be adjusted based
      on 5-FU pharmacokinetic (PK) monitoring. Although benefits of PK monitoring of 5
      FU in metastatic colorectal cancer (CRC) have been reported, its utility among
      patients with early stage disease has not been reported. PATIENTS AND METHODS: We
      retrospectively examined the effect of 5-FU PK monitoring in 84 CRC patients (49
      stage IV and 35 stage II/III) receiving mFOLFOX6 (modifiedFOLFOX6; modified 5
      fluorouracil, leucovorin, oxaliplatin protocol) or mFOLFIRI (modified 5
      fluorouracil, leucovorin, irinotecan protocol). Forty-six of the 84 patients
      received 5-FU doses based on BSA and 38 received doses that were adjusted with PK
      monitoring. 5-FU plasma levels were measured using a nanoparticle immunoassay
      method. RESULTS: 5-fluorouracil PK monitoring significantly improved disease-free
      survival in stage II/III patients (P = .0429). There was also a trend towards
      improved progression-free survival among stage IV patients who had their 5-FU
      levels PK-monitored (P = .16). Moreover, 5-FU PK monitoring significantly reduced
      (P = .0437) and delayed (P = .0144) adverse effects in stage II/III patients.
      Toxicity occurred after the second 5-FU dose in the BSA group and after the sixth
      to seventh dose in the PK monitoring group. In stage IV patients, the onset of
      toxicities was also delayed with PK monitoring (P = .0605). CONCLUSION: We
      provide evidence that PK monitoring of 5-FU is potentially beneficial for late
      stage and early stage CRC. These results contribute to the growing body of
      evidence regarding patient benefit when treatment decisions are based on the
      individual patient characteristics, in this case, a patients' 5-FU levels.

PMID- 24461503
TI  - Multifocal intraocular lenses: relative indications and contraindications for
      implantation.
AB  - This article presents an extensive overview of best clinical practice pertaining
      to selection and use of multifocal intraocular lenses (IOLs) currently available
      in the United States. Relevant preoperative diagnostic evaluations, patient
      selection criteria, counseling, and managing expectations are reviewed, as well
      as how to approach patients with underlying ocular intricacies or challenges and
      best practices for intraoperative challenges during planned implantation of a
      multifocal IOL. Managing the unhappy multifocal IOL patient if implantation has
      been performed is also addressed. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 24461502
TI  - Effect of total lens epithelial cell destruction on intraocular lens fixation in
      the human capsular bag.
AB  - PURPOSE: To evaluate the effect of complete destruction of lens epithelial cells
      (LECs) in the capsular bag on intraocular lens (IOL) stability. SETTING: School
      of Biological Sciences, University of East Anglia, Norwich, United Kingdom.
      DESIGN: Comparative evaluation. METHODS: An in vitro organ culture model using
      the bag-zonule-ciliary body complex isolated from fellow human donor eyes was
      prepared. A capsulorhexis and fiber extraction were performed, and an Acrysof IOL
      was implanted. Preparations were secured by pinning the ciliary body to a
      silicone ring and maintaining it in 6 mL Eagle minimum essential medium
      supplemented with 5% v/v fetal calf serum and 10 ng/mL transforming growth factor
      beta2 for 3 weeks or more. One bag of each pair was treated with 1 MUM
      thapsigargin to destroy all LECs. Observations of LEC growth were captured by
      phase-contrast microscopy, IOL stability by video microscopy, and endpoint
      analysis through scanning electron microscopy and immunocytochemistry. RESULTS:
      The LECs in control capsular bags migrated centrally, closing the bag and
      fixating the IOL between the anterior and posterior capsules, as seen clinically.
      These events were not observed in the thapsigargin-treated group. After a period
      of controlled orbital movement, the IOL in the control group stabilized quicker
      than in the treated bags. There was no IOL rotation in the bag; however, the IOLs
      in the treated group rocked with axial movement. CONCLUSIONS: The LECs appeared
      to aid stabilization of current IOL designs in the capsular bag. The results have
      clinical implications for IOL design and for strategies to prevent posterior
      capsule opacification. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24461500
TI  - Refractive surprise after toric intraocular lens implantation: graph analysis.
AB  - PURPOSE: To determine the refractive cylinder effect of rotating a toric
      intraocular lens (IOL) and identify the sources of refractive astigmatic surprise
      after toric IOL implantation. SETTING: Private practice, Melbourne, Australia.
      DESIGN: Experimental study. METHODS: Vergence formulas using a standard reduced
      eye model were used to bring all lens powers to the corneal plane. Double-angle
      vector diagrams were then used to (1) determine the refractive cylinder effect of
      rotating a toric IOL and (2) show how the prevailing astigmatism and the various
      planning and surgical steps involved in implanting a toric IOL contribute to the
      postoperative manifest refractive cylinder. RESULTS: An example calculation is
      given to illustrate the method. CONCLUSIONS: Refractive cylinder surprises can
      occur after toric IOL implantation. Understanding the causes enables surgeons to
      address contributory factors and choose an appropriate surgical method for
      managing individual cases of refractive cylinder surprise. 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- 24461493
TI  - Synthesis and biological evaluation of coumarin replacements of novobiocin as
      Hsp90 inhibitors.
AB  - Since Hsp90 modulates all six hallmarks of cancer simultaneously, it has become
      an attractive target for the development of cancer chemotherapeutics. In an
      effort to develop more efficacious compounds for Hsp90 inhibition, novobiocin
      analogues were prepared by replacing the central coumarin core with naphthalene,
      quinolinone, and quinoline surrogates. These modifications allowed for
      modification of the 2-position, which was previously unexplored. Biological
      evaluation of these compounds suggests a hydrophobic pocket about the 2-position
      of novobiocin. Anti-proliferative activities of these analogues against multiple
      cancer cell lines identified 2-alkoxyquinoline derivatives to exhibit improved
      activity. 

PMID- 24461499
TI  - Long-term observation and evaluation of femtosecond laser-assisted thin-flap
      laser in situ keratomileusis in eyes with thin corneas but normal topography.
AB  - PURPOSE: To evaluate the long-term outcomes of thin-flap laser in situ
      keratomileusis (LASIK) in eyes with thin corneas (central corneal thickness [CCT]
      <500 MUm) but normal topography. SETTING: Private center, Tokyo, Japan. DESIGN:
      Retrospective randomized comparative study. METHOD: The efficacy, safety,
      predictability, and topography of LASIK were evaluated in eyes with a CCT of less
      than 500 MUm but with normal topography (thin-cornea group) to 6 years
      postoperatively. The LASIK outcomes in the thin-cornea group were compared with
      those in eyes with a CCT of 500 MUm or greater (control group). Analysis was
      performed to determine whether there were differences between the groups at the
      last checkup 3 to 4 years postoperatively. RESULTS: In the thin-cornea group (291
      eyes; 146 patients), no significant differences were observed in LASIK outcomes
      when eyes were subdivided by the time of final checkup (3, 4, and >= 5 years).
      There was a significant difference in visual and refractive outcomes between 3
      months postoperatively and the last checkup in the thin-cornea group and the
      control group (371 eyes; 193 patients). No significant difference in visual,
      refractive, or topography outcomes was observed between the 2 groups at the last
      checkup. CONCLUSIONS: Laser in situ keratomileusis in eyes with thin corneas was
      as safe and effective as and showed similar long-term stability in eyes with a
      CCT of 500 MUm or greater. No eye in either group had a postoperative
      complication. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24461505
TI  - Detection of Escherichia fergusonii by PCR-based DNA sequencing in a case of
      delayed-onset chronic endophthalmitis after cataract surgery.
AB  - We report a case of chronic low-grade endophthalmitis after cataract surgery
      presenting with recurrent episodes of severe anterior chamber reactions and
      hypopyon uveitis caused by Escherichia fergusonii, which was isolated from
      vitreous aspirate by polymerase chain reaction-based DNA sequencing. Polymerase
      chain reaction has emerged as an essential, powerful, and rapid laboratory
      diagnostic technique and a useful adjunct to the conventional gold standard.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 24461501
TI  - Accommodation amplitudes after an accommodating intraocular lens refilling
      procedure: in vivo update.
AB  - PURPOSE: To evaluate whether a new capsular bag-refilling procedure provides some
      accommodation in monkey eyes and to assess the difference in accommodation with
      different volumes of capsular bag refilling. SETTING: Jinshikai Medical
      Foundation, Nishi Eye Hospital, Osaka, Japan. DESIGN: Experimental study.
      METHODS: A central 3.0 to 4.0 mm continuous curvilinear capsulorhexis was
      created, after which phacoemulsification was performed in the usual manner. A new
      accommodating-membrane intraocular lens (IOL) for sealing the capsular opening
      was implanted in the capsular bag. Silicone polymers were injected beneath the
      IOL into the capsular bag through the delivery hole. In 3 study groups, each with
      6 monkey eyes, the lens capsule was refilled with 0.080 mL of silicone polymers,
      corresponding to a 65% bag volume; 0.100 mL, corresponding to an 80% bag volume;
      or 0.125 mL, corresponding to a 100% bag volume. To calculate the accommodation
      amplitudes achieved, automated refractometry was performed before and 1 hour
      after topical pilocarpine 4.0% application preoperatively and 4 weeks
      postoperatively. RESULTS: The refilling technique was successful without polymer
      leakage in all monkeys. Four weeks after surgery, the mean accommodation
      amplitudes were 2.56 diopters (D) +/- 0.74 (SD), 2.42 +/- 1.00 D, and 2.71 +/-
      0.63 D, respectively, in the 3 study groups. CONCLUSIONS: The technique provided
      some accommodation in young monkey eyes. Leakage of the injectable silicone
      polymers and anterior capsule opacification in the visual axis were avoided. The
      results suggest that the capsular bag-refilling procedure warrants further study
      for possible clinical application. FINANCIAL DISCLOSURE: All authors have a
      proprietary interest in the accommodating membrane IOL mentioned in the article.

PMID- 24461507
TI  - Peripheral iridotomy to prevent Argentinian flag sign during capsulorhexis in the
      white cataract.

PMID- 24461498
TI  - Time and cost of teaching cataract surgery.
AB  - PURPOSE: To compare the differences in the time of completion of cataract surgery
      for residents and attending surgeons and to assign a dollar cost. SETTING:
      University of Colorado teaching hospital, Aurora, Colorado, USA. DESIGN:
      Comparative case series. METHODS: Cataract cases were divided into 3 levels of
      difficulty for comparison. Main outcome measures were total case time (incision
      to patch) and degree of difficulty. RESULTS: Nine residents and 6 attending
      surgeons participated in the study. Case times were collected for 324 resident
      cases and 319 attending surgeon cases. The mean attending surgeon case time was
      25.75 minutes +/- 12.32 (SD) and the mean resident case time, 46.35 +/- 16.75
      minutes. There was no significant difference in the degree of difficulty between
      resident cases and attending surgeon cases. Approximately 600 total cases were
      performed by 4 residents during 3 years of residency training. Taking into
      account the mean time of case completion for attending surgeons versus residents,
      the total difference in time if attending surgeons had performed 600 cataracts
      would be 12,360 minutes. Using a dollar cost of approximately $11.24 per minute
      at the institution, the cost difference was calculated to be $138,926.40.
      CONCLUSION: There was a significant time and dollar cost incurred in teaching
      cataract surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24461504
TI  - Intraocular polyimide intraocular lens haptic breakage long-term postoperatively.
AB  - We present 2 cases of 3-piece silicone intraoculanbsp;r lenses (IOLs) with broken
      polyimide haptics. In the first case, the IOL was implanted in the anterior
      chamber after posterior capsule rupture. Twelve years later, it was explanted and
      exchanged because of bullous keratopathy. However, on careful manipulation for
      explantation, the haptics shattered into multiple pieces. In the second case,
      initial in-the-bag implantation of the IOL was uneventful. Fifteen years later,
      the IOL dislocated into the anterior chamber as a result of spontaneous in situ
      haptic breakage. The haptics of both IOLs appeared very brittle during careful
      manipulation for gross and light microscopy, with further breakage. Scanning
      electron microscopy of both IOLs revealed no evidence of haptic degradation.
      Their surfaces appeared smooth and regular with jagged edges where the breaks
      occurred. Few studies have examined the long-term biocompatibility of polyimide,
      and more research is needed to determine the cause of this phenomenon. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24461494
TI  - Synthesis and biological evaluation of a new series of ebselen derivatives as
      glutathione peroxidase (GPx) mimics and cholinesterase inhibitors against
      Alzheimer's disease.
AB  - A series of ebselen derivatives were designed, synthesised and evaluated as
      inhibitors of cholinesterases (ChEs) and glutathione peroxidase (GPx) mimics.
      Most of the compounds were found to be potent against AChEs and BuChE, compounds
      5e and 5i, proved to be the most potent against AChE with IC50 values of 0.76 and
      0.46 MUM, respectively. Among these hybrids, most of the compounds were found to
      be good GPx mimics compare with ebselen. The selected compounds 5e and 5i were
      also used to determine the catalytic parameters and in vitro hydrogen peroxide
      scavenging activity. The results indicate that compounds 5e and 5i may be
      excellent multifunctional agents for the treatment of AD.

PMID- 24461506
TI  - Alternaria keratitis and hypopyon after clear-cornea phacoemulsification.
AB  - We report a case of Alternaria keratitis and hypopyon following clear-corneal
      cataract surgery. A 66-year-old woman presented with a painful red left eye
      several months after uneventful self-sealing clear-corneal phacoemulsification
      that was unresponsive to prolonged treatment with topical/oral quinolones and
      topical corticosteroids. A full-thickness stromal white dense infiltrate in the
      area of the intrastromal tunnel incision and a 2.0 mm hypopyon were observed.
      Culture from corneal scrapings revealed Alternaria species. Treatment included
      topical and subconjunctival injections of amphotericin-B (5 mg/mL) and 200 mg of
      oral ketoconazole. Complete resolution of the corneal infiltration and hypopyon
      was observed after 30 days of treatment, with no recurrence during 6 years of
      follow-up. To our knowledge, this is the first report of Alternaria species
      keratitis complicating self-sealing clear-corneal cataract surgery. Topical and
      subconjunctival injections of amphotericin-B and oral ketoconazole were effective
      in resolving the corneal abscess and anterior chamber inflammatory reaction.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 24461508
TI  - Clinically significant deterioration in the quality of vision as a result of
      subsurface nanoglistenings in a hydrophobic acrylic intraocular lens.

PMID- 24461510
TI  - February consultation #2.

PMID- 24461511
TI  - February consultation #3.

PMID- 24461513
TI  - February consultation #5.

PMID- 24461512
TI  - February consultation #4.

PMID- 24461509
TI  - Cataract surgical problem: February consultation #1.

PMID- 24461515
TI  - Hypnic headache: a descriptive study of 25 new cases in Brazil.
AB  - Our aim was to show the clinical characteristics of 25 patients with hypnic
      headache. We reviewed the medical records of 11,360 patients who complained of
      headache and selected those with hypnic headache, according to the criteria of
      the International Classification of Headache Disorders-2. Twenty-five patients
      (20 women and 5 men) were diagnosed with hypnic headache. The average age at the
      headache onset was 65.6 +/- 11.4 years (95% CI 61.1-70.1), ranging from 51 to 89
      years. The diagnosis of hypnic headache was made 3.0 +/- 2.7 years (95% CI 1.9
      4.0) after the headache started. Fourteen patients (56.0%) were awakened between
      4:00 and 6:00 a.m. The headache lasted for more than 2h in 16 (64.0%) patients.
      The headache was bilaterally localized (16/25; 64.0%), had a dull character
      (18/25; 72.0%) and a moderate intensity (17/25; 68.0%). The frequency was greater
      than 15 days per month (14/25; 56.0%). Associated symptoms were reported by 7
      patients: nausea (71.4%) and phonophobia (28.6%). There was successful treatment
      with lithium carbonate in 16/22 (72.7%) of the patients. Hypnic headache occurs
      exclusively during sleep in the elderly and especially in women. Lithium is an
      effective drug for its treatment.

PMID- 24461517
TI  - Antagonism of microRNA-99a promotes cell invasion and down-regulates E-cadherin
      expression in pancreatic cancer cells by regulating mammalian target of
      rapamycin.
AB  - MicroRNA-99a (miRNA-99a), a potential tumor suppressor, has been implicated in
      tumorigenesis of many human malignancies. However, the role of miRNA-99a in
      pancreatic cancer remains unclear. In the present study, we transfected miRNA-99a
      antagonism into human pancreatic cancer AsPC-1 cells to inhibit miRNA-99a
      expression and investigated its influence on cell migration and invasion as well
      as the underlying possible mechanisms. We found that miRNA-99a antagonism
      significantly increased proliferation, migration and invasion abilities of AsPC-1
      cells, which was accompanied by increased expression of mesenchymal phenotype
      cell biomarkers (N-cadherin, Vimentin, and alpha-SMA), and decreased expression
      of epithelial phenotype cell biomarker (E-cadherin). Interestingly, small
      interfering RNA (siRNA)-mediated knockdown of mammalian target of rapamycin
      (mTOR) remarkably restored miRNA-99a antagonism-induced down-regulation of E
      cadherin. In conclusion, our data suggest that miRNA-99a is involved in
      pancreatic cancer migration and invasion by regulating mTOR, and may provide a
      target for effective therapies against pancreatic cancer. 

PMID- 24461518
TI  - Ionotropic purinergic receptors P2X in frog and turtle retina: glial and neuronal
      localization.
AB  - Purinergic signaling is represented in both the peripheral and central nervous
      system (CNS), and in particular in the retina, which may be regarded as a part of
      the CNS. While purigenic signaling is relatively well studied in mammalian
      retinas, little is known about it in retinas of lower vertebrates. The aim of
      present study was to investigate, using immunocytochemistry, the distribution of
      purinoreceptors P2X in retinas of frog and turtle, which are appropriate models
      of the brain neuron-to-glia interactions. The results showed widespread
      expression of all seven ionotropic purinoreceptors (P2X1-P2X7) in both frog and
      turtle retinas. They were predominantly expressed in Muller cells, the principal
      glial cells in the retina. All structures typical of Muller cells: the outer and
      the inner limiting membranes, the cells bodies in the inner nuclear layer, the
      radial processes in the inner plexiform layer (IPL), and the so called endfeet
      (frog) or the orthogonal arrays of particles (turtle) in the ganglion cells layer
      were immunostained. Colocalizations between P2X1-P2X7 and the glial cell marker
      Vimentin proved that the immunostaining was in the Muller cells. In addition to
      the glial staining, neuronal staining was also seen as fine puncta in the inner
      plexiform layer and by small dots and patches in the outer plexiform layer. Some
      cell bodies of horizontal, amacrine and ganglion cells were also stained. The
      results obtained imply that the purinergic P2X receptors may significantly
      contribute to the neuron-to-glia signaling in retinas of the lower vertebrates. 

PMID- 24461519
TI  - Heterologous expression, chaperone mediated solubilization and purification of
      parasitic nematode-specific growth factor-like protein of Setaria digitata.
AB  - OBJECTIVE: To clone, express and purify a putative parasitic nematode specific
      protein of Setaria digitata (S. digitata), filarial nematode that infects
      livestock and cause significant economic losses in Far East and Asia to be used
      for structural and functional analyses. METHODS: To characterize uncharacterized
      gene of S. digitata (SDUG), the herterologous expression of SDUG was carried out
      in the pET [cloned into pET45b(+)] expression system initially and co-expression
      of SDUG using chaperone plasmids pG-KJE8, pGro 7, pKJE7, pG-Tf2 and pTf16
      containing chaperone proteins of dnaK-dnaJ-grpE-groES-gro-E, groES-groEL, dnaK
      dnaJ-grpE, groES-groEL-tig, and tig respectively, was carried out subsequently.
      RESULTS: Expression of SDUG was seen when Escherichia coli strain BL21(DE3) is
      used, while concentrating protein largely into the insoluble fraction. The co
      expression of SDUG using chaperone plasmid mediated system indicated a
      significant increase of the protein in the soluble fraction. Of the chaperon
      plasmid sets, the highest amount of recombinant SDUP in the soluble fraction was
      seen when pGro7 was used in the presence of 2 mg/mL L-arabinose and 0.6M IPTG
      concentration in the culture medium and for 3 h of incubation at the temperature
      of 28  degrees C. Recombinant SDUG was purified both from soluble and insoluble
      fractions using Ni affinity chromatography. SDS-PAGE and western blot analyses of
      these proteins revealed a single band having expected size of ~24 kDa.
      CONCLUSIONS: SDUG seems to be more aggregate-prone and hydrophobic in nature and
      such protein can make soluble by correct selecting the inducer concentrations and
      induction temperature and its duration.

PMID- 24461516
TI  - Contact mechanics studies of an ellipsoidal contact bearing surface of metal-on
      metal hip prostheses under micro-lateralization.
AB  - The morphology of the contact bearing surfaces plays an important role in the
      contact mechanics and potential wear of metal-on-metal (MOM) hip prostheses. An
      ellipsoidal bearing surface was proposed for MOM hip implants and the
      corresponding contact mechanics were studied by using the finite element method
      (FEM) under both standard and micro-lateralization conditions. When under micro
      lateralization, the maximum contact pressure decreased from 927.3MPa to 203.0MPa,
      with increased ellipticity ratio medial-laterally. And the contact region was
      found to shift from the rim of the cup to the inner region compared to the
      spherical design. Under standard conditions, an increasing trend of the maximum
      contact pressure for the acetabular component was predicted as the major radius
      of the ellipsoidal bearing surface was increased. Nevertheless, the maximum
      contact pressure reached an asymptotic value when the ellipticity ratio was
      increased to 1.04. Therefore it is critical to optimize the ellipticity ratio in
      order to reduce the contact pressure under micro-lateralization condition and yet
      not to cause a markedly increased contact pressure under normal condition.
      Additionally, the maximum contact pressure in the ellipsoidal bearing surface
      remained relatively constant with the increased micro-lateralization. It is
      concluded that an ellipsoidal bearing surface morphology may be a promising
      alternative by offering better contact mechanisms when micro-lateralization
      should occur and attributing to minimized wear. 

PMID- 24461520
TI  - First report on natural Leishmania infection of Phlebotomus sergenti due
      Leishmania tropica by high resolution melting curve method in South-eastern Iran.
AB  - OBJECTIVE: To identify the Leishmania species in infected sand flies by Real-time
      PCR coupled with HRM analysis. METHODS: Real-time PCR coupled with HRM analysis
      targeting the first internal transcribed spacer (ITS1) of nuclear ribosomal DNA
      as the genetic marker was used to identify and distinguish Leishmania species in
      sand flies specimens. RESULTS: Three out of 115 females of Phlebotomus sergenti
      (P. sergenti) (2.6%) were positive to Leishmania tropica (L. tropica).
      CONCLUSIONS: This is the first report on P. sergenti as the main and proven
      vector of anthroponitic cutaneous leishmaniasis in Dehbakri County using Real
      time PCR coupled with HRM analysis. This method is rapid, sensitive and specific
      for diagnosing of parasites in infected Sand flies and ideal for large scale
      genotyping projects.

PMID- 24461522
TI  - Evaluation of in vitro antioxidant and apoptotic activities of Cyperus rotundus.
AB  - OBJECTIVE: To evaluate in vitro antioxidant and apoptotic activities of Cyperus
      rotundus (C. rotundus). METHODS: The phytochemical study and the antioxidant
      activities of both methanol and aqueous extracts from C. rotundus aerial part
      were determined. In addition, these extracts were also investigated for their
      cytotoxic and apoptotic activities. The major compound of the methanol extract
      was isolated. Both methanol and aqueous extracts (300, 150, and 50 MUg/mL) were
      evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay
      system. However, 16, 8, and 4 mg/mL of each extract were tested to investigate
      their OH. formation scavenging potential. Aqueous extract (800, 400, and 200
      MUg/mL) and methanol extract (350, 175, and 88 MUg/mL) were tested against lipid
      peroxidation, induced by 75 MUM H2O2. The cytotoxicity (by MTT assay) and cell
      DNA fragmentation of both extracts were evaluated towards K562 and L1210 cell
      lines. The major compound was obtained from the butanol fraction of methanol
      extract and its structure was determined by RMN spectroscopic analysis. RESULTS:
      The methanol and aqueous extracts showed respectively, 88% and 19% inhibition of
      xanthine oxidase activity. Yet, the same extracts inhibited lipid peroxidation by
      61.5% and 42.0%, respectively. Both extracts inhibited OH. formation by 27.1% and
      25.3%, respectively. Only methanol extract induced DNA degradation. Orientin was
      determined as the major compound isolated from the butanol fraction of methanol
      extract. CONCLUSIONS: It appears that C. rotundus extracts exhibit a potential
      use as a natural antioxidant and an apoptosis inducer.

PMID- 24461528
TI  - Hepatic effect of NAC on sevear acute pancteatise of rats.
AB  - OBJECTIVE: To analyze the hepatic protection of n-acetyl cysteine (NAC) on severe
      acute pancreatitis (SAP). METHODS: SD rats were randomly divided into control
      group, SAP group and NAC group. SAP AHO method was adopted to establish the
      model, 2 h after modeling, rats in NAC group had intraperitoneal injection of NAC
      (200 mg/kg). Ten rats from each group were sacrificed in every 6 and 12 h at
      different time points respectively. Liver damage, liver function and serum
      amylase, AST, ALT and malondialdehyde (MDA) were determined. RESULTS: Serum
      amylase, AST, ALT and MDA content in SAP, NAC group at each time point were
      significantly higher in the control group (P<0.05), serum amylase, AST, ALT and
      MDA content in NAC group rats were lower in the SAP group significantly (P<0.05);
      Microscopic examination showed that the liver injury in rats and the NAC group
      significantly reduced in the SAP group. CONCLUSIONS: NAC provides effective
      protection against liver damage to SAP, protective from SAP liver injury.

PMID- 24461523
TI  - Antioxidant effects of Phyllanthus niruri tea on healthy subjects.
AB  - OBJECTIVE: To investigate the potential antioxidant effects of Phyllanthus niruri
      (P. niruri, Euphorbiaceae) tea on healthy subjects. METHODS: Five non-smoking,
      male healthy volunteers, 20 to 31 years old, were enrolled. Each subject was
      treated twice, following a randomized crossover fashion regarding the ingestion
      of P. niruri infusion (5 g/750 mL) (tea group) or 750 mL of water (control
      group). Fasting venous blood samples were collected prior to and at 1, 2 and 4 h
      after infusion drinking. Samples were tested for plasmatic gallic acid and
      ascorbic acid levels, erythrocytic catalase and superoxide dismutase activities,
      and intracellular DCFH fluorescence in granulocytes, monocytes and lymphocytes.
      RESULTS: Catalase and superoxide dismutase activities were not altered by tea
      ingestion. Plasma levels of gallic acid were significantly increased at 1, 2 and
      4 h after P. niruri ingestion and plasma ascorbic acid at 1 h after P. niruri
      ingestion. CONCLUSIONS: Ingestion of P. niruri tea is associated with a slight
      increase in antioxidant markers in human blood (ascorbic acid and gallic acid),
      which may contribute to its pharmacological effects.

PMID- 24461524
TI  - Recovery of Cyclospora cayetanensis among asymptomatic rural Thai schoolchildren.
AB  - OBJECTIVE: To obtain the prevalence with clinical symptoms of Cyclospora
      cayetanensis (C. cayetanensis), a coccidian protozoan parasite, in Thailand which
      is the cause of an intestinal infection characterized by sporadic-to-frequent
      explosive diarrhea. METHODS: In a field survey conducted by the Faculty of
      Tropical Medicine, Mahidol University, as part of the existing parasite-control
      program, a total of 2 540 faecal samples from villagers in Nan Province,
      Thailand, were collected and examined to determine the prevalence and clinical
      characteristics of parasitic infections. RESULTS: Twelve cases of C. cayetanensis
      infection were found during faecal examination of schoolchildren aged 5-12 years.
      None exhibited obvious clinical symptoms, especially evidence of diarrhea; 5 of
      12 had loose faeces, one reported frequent symptoms of abdominal discomfort, and
      another had pale conjunctiva with low hematocrit. The children were generally
      asymptomatic. CONCLUSIONS: This finding confirms a public-health issue with
      potentially serious consequences whereby children can be exposed to an
      environment contaminated with food-and water-borne transmitted oocysts, and can
      hence become infected with C. cayetanensis.

PMID- 24461521
TI  - Antimalarial potential of kolaviron, a biflavonoid from Garcinia kola seeds,
      against Plasmodium berghei infection in Swiss albino mice.
AB  - OBJECTIVE: To investigate the antimalarial potential of kolaviron (KV), a
      biflavonoid fraction from Garcinia kola seeds, against Plasmodium berghei (P.
      berghei) infection in Swiss albino mice. METHODS: The study consists of seven
      groups of ten mice each. Groups I, II and III were normal mice that received corn
      oil, KV1 and chloroquine (CQ), respectively. Groups IV, V, VI and VII were
      infected mice that received corn oil, CQ, KV1 and KV2, respectively. CQ, KV1 and
      KV2 were given at 10-, 100- and 200-mg/kg daily, respectively for three
      consecutive days. RESULTS: Administration of KV1 and KV2 significantly (P<0.05)
      suppressed P. berghei-infection in the mice by 85% and 90%, respectively, while
      CQ produced 87% suppression relative to untreated infected group after the fifth
      day of treatment. Also, KV2 significantly (P<0.05) increased the mean survival
      time of the infected mice by 175%. The biflavonoid prevented a drastic reduction
      in PCV from day 4 of treatment, indicating its efficacy in ameliorating anaemia.
      Significant (P<0.05) oxidative stress assessed by the elevation of serum and
      hepatic malondialdehydewere observed in untreated P. berghei-infected mice.
      Specifically, serum and hepatic malondialdehyde levels increased by 93% and 78%,
      respectively in the untreated infected mice. Furthermore, antioxidant indices,
      viz; superoxide dismutase, catalase, glutathione-s-transferase, gluathione
      peroxidase and reduced gluathione decreased significantly (P<0.05) in the tissues
      of untreated P. berghei-infected mice. KV significantly (P<0.05) ameliorated the
      P. berghei-induced decrease in antioxidant status of the infected mice.
      CONCLUSIONS: This study shows that kolaviron, especially at 200 mg/kg, has high
      antimalarial activities in P. berghei-infected mice, in addition to its known
      antioxidant properties.

PMID- 24461533
TI  - Diagnosis and multi-modality treatment of adult pulmonary plastoma: Analysis of
      18 cases and review of literature.
AB  - The clinical data of 18 patients with PB from April 1989 to April 2013 was
      analyzed retrospectively, including 11 men and 7 women, aged 45 and 76 years old
      (mean 53 years). There were 12 cases of PB occurring in right lung and other
      cases in left lung. Among them, 3 patients had no symptoms, and 15 patients
      displayed symptoms of cough, chest pain, asthenia or minor haemoptysis. Overall,
      11 patients had a preoperative diagnosis of lung cancer, 7 patients were
      preoperatively diagnosed as the other diseases, which included lung benign tumor
      (n=5) and mediastinal mass (n=2). All patients received a radical resection. Six
      patients received postoperative cisplatin-based chemotherapy, and two patients
      received postoperative irradiation with the dose of 55 Gy. Histologically, 14
      cases of 18 patients had biphasic pulmonary blastoma and four cases had well
      differentiated fetal adenocarcinoma. A total of 12 patients died in a period of 6
      36 months after operation, and 1 case was lost after 2 years of follow up. The
      median survival time was 19 months. PB is a rare primary lung malignant embryonal
      neoplasm. Despite its assumed embyonal origin, the tumor has a predilection for
      adults. A preoperative correct diagnosis is very difficult in spite of modern
      diagnostic imaging and biopsy techniques. Surgical resection is the main method
      for diagnosis and treatment. Postoperative chemotherapy or irradiation can help
      eliminate tumor remnants. Its prognosis is very poor, especially for the biphasic
      type. 

PMID- 24461532
TI  - Mathematical modeling for selecting center locations for medical and health
      supplies reserve in Hainan Province.
AB  - OBJECTIVE: To explore how to choose the center locations to build the medical and
      health supplies reserve among many island towns. METHODS: The center locations
      were selected from 18 towns Hainan Province, it's maximum service range
      (distance) was required to reach the minimum, or to minimize. RESULTS: Three
      scenarios were considered, the center locations included only one town, two
      towns, three towns. By the use of graph theory and MATLAB programming, a
      mathematical model was established to obtain the shortest distance and the
      shortest path between arbitrary two towns. CONCLUSIONS: We find out the center
      sites under certain conditions, and determine the specific service ranges of the
      center sites.

PMID- 24461531
TI  - Bond strength analysis of the bone cement- stem interface of hip arthroplasties.
AB  - OBJECTIVE: To study and establish the preliminary linear and modified models for
      the interface shear mechanics performance between implant and bone cement and to
      explore its damage significance. METHOD: The loosening research between
      artificial hip joint prosthesis stem and bone cement interface performance can be
      evaluated by the push-in test. Based on the debonding performance test, the
      analytical expressions of the average load and displacement from the debonding
      failure and splitting failure process were deduced and determined. The
      correlations of the expressions of the average load-displacement and statistical
      experimental data were analyzed. RESULTS: It demonstrated that the interface
      debonding failure mechanical model could be characterized as interface bond
      strength mechanical performance. Based on analysis of models and experimental
      data by the three statistical analysis methods, the results indicated the
      modified model could be better represented by the interfacial debonding strength
      properties. The bond stress tau and relative sliding s distribution along the
      embedment regional were coupling affected by both pressure arch effect and shear
      lag effect in bone cement. Two stress peaks of implant have been found at the
      distance from 0.175La loading tip to 0.325La free tip, which also verified the
      early loosening clinical reports for the proximal and latter region. As the bone
      cement arch effect, the bond stress peak tend to move to the free tip when the
      debonding failure would be changed into the splitting failure, which presents a
      preliminary study on the mechanism of early debonding failure for the stem-cement
      interface. CONCLUSIONS: Functional models of the stem-bone cement interfacial
      debonding failure are developed to analyze the relevant mechanism. The different
      locational titanium alloy stress, and the interfacial bond stress and the
      relative slides are evaluated to acquire a guide of the different positions of
      interfacial damage. The coupling effect which is original from the pressure arch
      and the interfacial shear hysteresis cumulative effect has influence on the
      interfacial debonding and damage process.

PMID- 24461525
TI  - Co-positivity of anti-dengue virus and anti-Japanese encephalitis virus IgM in
      endemic area: co-infection or cross reactivity?
AB  - OBJECTIVE: To report high co-positivity of anti-dengue virus (DV) and anti
      Japanese encephalitis virus (JEV) IgM in an area endemic for both the viruses and
      to discuss the possibilities of co-infection. METHODS: Serum samples from the
      patients who presented with fever, suspected central nervous system infection and
      thrombocytopenia, were tested for anti-DV IgM and anti-JEV IgM antibodies.
      Conventional reverse transcriptase polymerase chain reaction was done for
      detection of DV RNA and JEV RNA. RESULTS: Of 1 410 patient sera tested for anti
      DV and anti-JEV antibodies, 129 (9.14%) were co-positive for both. This co
      positivity was observed only in those months when anti-JEV IgM positivity was
      high. Titers of both anti-DV IgM and anti-JEV IgM were high in most of the co
      positive cases. Among these 129 co-positive cases, 76 were tested by conventional
      reverse transcriptase polymerase chain reaction for both flaviviruses, of which
      eight cases were co-positive for DV and JEV. CONCLUSIONS: Co-infection with more
      than one flavivirus species can occur in hyperendemic areas.

PMID- 24461514
TI  - Prognostic implications of chromosome 17 abnormalities in the context of
      monosomal karyotype in patients with acute myeloid leukemia and complex
      cytogenetics.
AB  - BACKGROUND: Chromosome 17 abnormalities are associated with poor outcome in
      leukemias including AML. Recently, MK was introduced as an independent predictor
      of dismal outcome in AML. The additional prognostic effect of C17 abns in
      patients with MK in a CK background is not clear. PATIENTS AND METHODS: We
      conducted a retrospective analysis of 1086 patients with newly diagnosed AML
      treated between January 1998 and December 2007. Patients received treatment with
      one of the institution's first-line protocols. RESULTS: Four hundred eighty-three
      patients had CK. Among them, 370 patients (77%) had CK-MK, and 195 patients (53%)
      had CK-MK-C17 abns. Patients with CK-MK had significantly shorter OS rates
      compared with patients with CK without MK (4.4 vs. 8 months, respectively; P =
      .002). The median OS for patients with CK-C17 abns was shorter than for patients
      without C17 abns (4 vs. 6.1 months, respectively; P = .004). In a multivariate
      analysis, the presence of MK among patients with CK was identified as an
      independent prognostic marker for OS. In addition, presence of C17 abns had a
      significant negative effect on OS among patients with CK-MK (P = .04).
      CONCLUSION: Among patients with CK-AML, MK was associated with poor outcomes.
      Additional presence of C17 abns further worsens the outcome in these particularly
      poor-risk patients with AML.

PMID- 24461535
TI  - Unconscious influences of, not just on, decision making.
AB  - This commentary focuses on the bidirectional links between unconscious influences
      and decision making. In particular, it examines the extent to which awareness is
      (not) necessary to the impact of decisions on psychological processes such as
      preferences. This analysis might help researchers to gain an extended perspective
      of Newell & Shanks' (N&S's) concerns regarding the role of unconscious influences
      in theories of decision making. 

PMID- 24461527
TI  - Preparation of novel biodegradable pHEMA hydrogel for a tissue engineering
      scaffold by microwave-assisted polymerization.
AB  - OBJECTIVE: To prepare a novel biodegradable poly(2-hydroxyethylmethacrilate)
      (pHEMA) hydrogel as tissue engineering scaffold. METHODS: The pHEMA hydrogel was
      synthesized by microwave-assisted polymerization using 2-hydroxyethyl
      methacrylate (HEMA) as the raw material, potassium persulfate as the initiator,
      and PCLX as the cross-linking additive. The hydrogels was characterized with FTIR
      and NMR spectroscopy. The physical and chemical properties of the prepared
      hydrogel were evaluated, and its degradation performance was tested. The
      cytotoxicity of the optimum composite hydrogel was measured by an MTT assay to
      confirm the feasibility of its use in tissue engineering. RESULTS: The optimum
      conditions under which the hydrogel was prepared by microwave-assisted
      polymerization are as follows: 1.5 g cross-linking additive, 0.3 g initiator,
      reaction temperature of 80  degrees C, and microwave power of 800 W. Degradation
      studies showed good degradation profiles with 75% in 17 days. Additionally, the
      hydrogels did not elicit any cytotoxic response in in vitro cytotoxic assays.
      CONCLUSION: A biodegradable pHEMA hydrogel was successfully prepared by microwave
      assisted polymerization, as confirmed from FTIR and NMR results. The hydrogel
      shows promising applications in tissue engineering, and its healing ability and
      biocompatibility will be evaluated in detail in the future.

PMID- 24461529
TI  - Comparative analysis of different cyclosporine A doses on protection after
      myocardial ischemia/reperfusion injury in rat.
AB  - OBJECTIVE: To investigate the protective effect of different cyclosporin A (CsA)
      doses on myocardial ischemia/reperfusion injury in rat models. METHODS: A rat
      model of myocardial ischemia/reperfusion injury was established in vivo and the
      rats were randomly divided into four groups: placebo (PBS; T1), low-dose (CsA
      dose: 1.0 mg/kg; T2), medium-dose (CsA dose: 2.5 mg/kg; T3), and high-dose (CsA
      dose: 5.0 mg/kg; T4) groups. Heart function indexes were monitored at different
      time points, the extent of myocardial infarction was assessed by Evans Blue-TTC
      staining, and creatine kinase MB mass and cardiac troponin I values were measured
      by biochemical assays. RESULTS: Compared with the T1 and T2 groups, both the
      creatine kinase MB mass and cardiac troponin I were significantly lower in the T3
      and T4 groups (P<0.05). The mean arterial pressure (MAP) and left ventricular
      systolic pressure (LVSP) decreased sequentially in each group, with the extending
      reperfusion time. Significant decreases in LVSP and MAP were observed in the T3
      and T4 groups as compared to the T1 and T2 group (P<0.05), and the T2 group
      showed a significantly lower LVSP and MAP decline than the T1 group (P<0.05).
      Compared with the T1 group, the rats from the T2, T3, and T4 groups suffered from
      a significantly lower extent of myocardial infarction (P<0.05). Also, the animals
      in the T3 and T4 groups had a significantly smaller extent of myocardial
      infarction than those in the T2 group (P<0.05). CONCLUSIONS: Various CsA doses
      exert different degrees of protection against ischemia/reperfusion injury, and
      this protective effect peaks at approximately 2.5 mg/kg in rat models.

PMID- 24461530
TI  - Comparison on serum biomarkers for anovulatory and ovulatory dysfunctional
      uterine bleeding in Lizu females.
AB  - OBJECTIVE: To screen, identify, and compare the serum biomarkers between
      anovulatory dysfunctional uterine bleeding (ADUB) and ovulatory dysfunctional
      uterine bleeding (ODUB) in Lizu females. METHODS: The subjects included 128 ADUB
      patients, 63 ODUB patients, and 93 controls. The serum and supernate of the
      subjects' mense were collected and stored at -80  degrees C until use.
      Differential proteins in the sera of three groups were screened using surface
      enhanced laser desorption ionization time-of-flight mass spectrometry. The
      screened proteins were then identified by tricine-SDS-PAGE gel and spectrometry.
      Protein expression levels in the menses of ADUB, ODUB, and control subjects were
      determined using ELISA, RT-PCR, and Western blotting. SPSS 14.1 was used for
      statistical analysis and chart drawing (alpha = 0.05). RESULTS: Three
      differential protein peaks with peak values of 11.80, 13.59, and 14.68 km/z were
      screened and identified as serum amyploid protein A (SAA), vascular endothelial
      growth factor, and vitamin K epoxide reductase, respectively. The SAA was highly
      expressed in the menses of ADUB and ODUB patients but poorly expressed in the
      controls. The vascular endothelial growth factor was highly expressed in the
      menses of ODUB and controls but poorly expressed in ADUB patients. Meanwhile, the
      vitamin K epoxide reductase was highly expressed in the menses of ADUB and
      control subjects but poorly expressed in ODUB patients. CONCLUSIONS: The SAA is
      the common serum biomarker of ADUB and ODUB. ADUB may be related to angiogenesis
      impairment, whereas ODUB may be associated with blood coagulation disruption.

PMID- 24461526
TI  - Enhancement of vitamin A combined vitamin D supplementation on immune response to
      Bacille Calmette-Guerin vaccine revaccinated in Chinese infants.
AB  - OBJECTIVE: To investigate whether there is an association between diameter of
      bacille Calmette-Guerin (BCG) scars and effect of purified protein derivative
      (PPD) reaction and to determine whether vitamin A (VA) combined vitamin D (VD)
      supplementation influences the immune response to BCG revaccinated in Chinese
      infants. METHODS: A cross-section and 3-month community-randomised trial was
      conducted. A total of 5 629 infants at 3, 6 and 12 months of age in Junan County
      of China were examined for BCG scar formation. Then, 597 revaccinated infants
      were randomly assigned to supplementation (n=307) and control (n=290) groups. The
      supplementation group were daily assigned to 1 500 IU VA and 500 IU VD for 3
      months. Then all infants were subjected to skin test with PPD. RESULTS: The
      diameter of BCG scars was positively correlated with diameter of skin indurations
      of PPD (r=0.17, P<0.05) in the 5 629 infants. The rate of positive response to
      PPD was higher in the supplementation group than in the control group (96.1%
      versus 89.7%, P<0.05, prevalence ratio 1.07, 95% CI 1.02-1.12). The prevalence
      ratio of PPD response for the supplementation group compared with that for the
      control group was 1.07 (95% CI 1.01-1.13) for the males and 1.08 (95% CI 1.00
      1.17) for the females. For the supplementation group, the males got larger
      tuberculin induration than the females [(0.73+/-0.21) cm versus (0.67+/-0.20) cm,
      P<0.05) after intervention. CONCLUSIONS: The diameter of BCG scars was
      effectively correlated with PPD response, which indicates BCG scar formation may
      be an useful tool to evaluate the effect of tuberculosis prevention. VA combined
      VD supplementation may play an immuno-regulatory role in BCG revaccination. This
      may contribute to the prevention of childhood tuberculosis.

PMID- 24461534
TI  - An accidental liraglutide overdose: case report.

PMID- 24461538
TI  - Maternal autoimmunity and adverse pregnancy outcomes.
AB  - Some of the most dangerous and costly complications of human pregnancy, including
      premature labor and preeclampsia/eclampsia, have remained unexplained. While not
      noted by the authors of a recently published study of three distinct groups of
      patients with thyroid disease, their data may offer new insights into the
      interplay between thyroid autoimmune disease, indeed possibly autoimmunity in
      general, and human pregnancy. This editorial discusses a report of 223,512
      pregnancies (2002-2008) from a retrospective U.S. cohort, the Consortium of Safe
      Labor, reported by Mannisto et al. from the Epidemiology Branch, Division of
      Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National
      Institute for Child Health and Human Development, National Institutes of Health,
      Rockville, Maryland in the July 2013 issue of The Journal of Clinical
      Endocrinology and Metabolism. Reading between the lines of this publication
      offers potential insights into the etiologies of preeclampsia/eclampsia and of
      term as well as premature labor. Moreover, this study, unintentionally, may also
      offer insights into currently still only poorly understood immune dysfunction
      that links autoimmunity with adverse pregnancy outcomes. 

PMID- 24461536
TI  - Diagnosis and classification of relapsing polychondritis.
AB  - Relapsing polychondritis is a rare and potentially fatal autoimmune disease of
      unknown etiology, characterized by inflammation and destruction of different
      cartilaginous structures, including the ear, nose, larynx, trachea, bronchi,
      peripheral joints, eye, heart and skin, with high risk of misdiagnosis. The
      spectrum of clinical presentations is protean and may vary from intermittent
      episodes of painful and disfiguring auricular and nasal chondritis or
      polyarthritis to severe progressive multi-organ damage. A laryngotracheobronchial
      involvement appears in nearly half of patients and is complicated by local
      obstructions, which may be life-threatening. A highly medical specialized
      approach is required for diagnosis of relapsing polychondritis. This review
      comprehensively examines the literature related to the clinical sceneries of the
      disease and focuses on both diagnostic tools used in clinical studies and recent
      findings related to its etiopathogenesis. 

PMID- 24461537
TI  - CD4(-)CD8(-) T-cells in primary Sjogren's syndrome: association with the extent
      of glandular involvement.
AB  - OBJECTIVES: Growing evidence suggests that IL-17-producing T cells, lacking both
      CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal
      role in the pathogenesis of a number of systemic autoimmune disorders. We
      recently demonstrated that this T-cell subset is expanded in the peripheral blood
      (PB) of patients with primary Sjogren's syndrome (pSS), produces IL-17 and
      accumulates in minor salivary glands (MSGs). We aimed to investigate glandular
      and PB DN T cells in early pSS in order to verify a possible correlation with
      MSGs histological patterns and clinical parameters. METHODS: Paired samples of PB
      mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by
      flow cytometry and immunofluorescence staining respectively. Histological
      analysis to identify histological scores, B/T cell segregation and the presence
      of germinal center (GC)-like structures was also performed. RESULTS: In early
      stages of pSS, circulating DN T cells appear to be not yet expanded and inversely
      correlated with circulating CD4(+)Th17 cells. The number of infiltrating DN T
      cells were associated with extent of glandular involvement, presence of GC-like
      structures and dryness symptoms and were inversely correlated with circulating DN
      T cells. CONCLUSIONS: Our findings suggest that DN T cells are actively involved
      in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS
      and may play a role in ectopic lymphoneogenesis development occurring during the
      disease.

PMID- 24461539
TI  - Diagnosis and classification of the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is defined by the occurrence of venous and
      arterial thromboses, often multiple, and recurrent fetal losses, frequently
      accompanied by a moderate thrombocytopenia, in the presence of antiphospholipid
      antibodies (aPL). Some estimates indicate that the incidence of the APS is around
      5 new cases per 100,000 persons per year and the prevalence around 40-50 cases
      per 100,000 persons. The aPL are positive in approximately 13% of patients with
      stroke, 11% with myocardial infarction, 9.5% of patients with deep vein
      thrombosis and 6% of patients with pregnancy morbidity. The original
      classification criteria for the APS were formulated at a workshop in Sapporo,
      Japan, in 1998, during the 8th International Congress on aPL. The Sapporo
      criteria, as they are often called, were revised at another workshop in Sydney,
      Australia, in 2004, during the 11th International Congress on aPL. At least one
      clinical (vascular thrombosis or pregnancy morbidity) and one laboratory
      (anticardiolipin antibodies, lupus anticoagulant or anti-beta2-glycoprotein I
      antibodies) criterion had to be met for the classification of APS. 

PMID- 24461540
TI  - Polymyalgia rheumatica--diagnosis and classification.
AB  - Polymyalgia rheumatica is the most common inflammatory rheumatic disease of the
      elderly, and shares many pathogenetic and epidemiological features with giant
      cell arteritis. The typical symptoms are bilateral aching of the shoulder girdle,
      associated with morning stiffness. The neck and hip girdle may also be involved.
      The diagnosis of polymyalgia rheumatica is made primarily on clinical grounds.
      There is no single diagnostic test, but sets of diagnostic or classification
      criteria have been suggested by several groups of investigators, based on the
      typical clinical presentation and laboratory evidence of acute-phase reaction.
      Other conditions that may mimic polymyalgia rheumatic, such as elderly-onset
      rheumatoid arthritis, must be excluded by appropriate testing and close
      monitoring of the disease course. Glucocorticoids at low doses (15-20 mg
      prednisone per day initially) are the mainstay of treatment.

PMID- 24461541
TI  - Adult supratentorial extra-pineal primitive neuro-ectodermal tumors.
AB  - Primitive neuro-ectodermal tumors (PNET) are rare malignant brain tumors, mostly
      undifferentiated, that tend to spread through the cerebrospinal fluid (CSF).
      Extra-pineal supratentorial PNET in adults are very rare. Published guidelines
      for adult PNET were not available until 2011, and at our institute surgeons and
      oncologists did not have consensus on imaging evaluation or treatment protocols
      between 1994 to 2008. Twenty-two consecutive adult patients with extra-pineal
      supratentorial PNET from this period were reviewed in this retrospective study.
      Their clinical profiles and radiologic images were evaluated. A pathological
      review based on the 2007 World Health Organization criteria was also conducted.
      Prognostic factors were analyzed. The 1 and 3 year overall survival rates were
      64% and 32% for adult extra-pineal supratentorial PNET, respectively. Limited by
      the small number of tumors in this series, we suggest that negative prognostic
      factors are multiplicity at onset, initial CSF seeding, and tumor
      differentiation. Although age of onset, extent of resection, radiation and
      chemotherapy were assumed to be good prognostic factors, the analysis did not
      reveal strong significance for overall survival with univariate and multivariate
      analysis. We believe more detailed investigations on the genetic/molecular basis
      of supratentorial PNET and their clinical outcomes are warranted.

PMID- 24461543
TI  - Long-term outcome of epilepsy surgery: a retrospective study in a population of
      379 cases.
AB  - We evaluated the long-term outcome of epilepsy surgery in drug-resistant epilepsy
      patients, and investigated preoperative factors associated with postoperative
      long-term surgical outcome. We performed a retrospective study of 379 patients
      who received epilepsy surgeries from 2000 to 2010. Patients had completed a
      minimum of 2-year and up to 12-year follow-up. Preoperative evaluations, surgical
      outcomes and clinical data of patients were collected and analyzed. We found that
      the epilepsy surgery was effective in drug-resistant patients and the long-term
      outcome of epilepsy surgery was satisfactory. The bipolar electro-coagulation
      could improve the surgical outcome when the epileptogenic focus was on the
      functional cortex. Results of the 2-year follow-up showed that preoperative
      seizure characteristics including the history of febrile seizure, seizure
      frequency, and location, quantity and range of seizure foci were significantly
      associated with the surgical outcome. The surgery procedure including the surgery
      type and the extent of resection also affected outcome. Abnormal head or
      hippocampus MRI, inconsistent results of preoperative investigations, seizure
      types, and pathology type might also be predictors of long-term surgical outcome.

PMID- 24461542
TI  - Three-dimensional assessment of vascular and perivascular characteristics in
      subjects with retinopathy of prematurity.
AB  - PURPOSE: To study vascular features detected with spectral domain optical
      coherence tomography (SD-OCT) in subjects undergoing retinopathy of prematurity
      (ROP) screening. DESIGN: Cross-sectional study. PARTICIPANTS AND CONTROLS: Fifty
      seven premature neonates, 10 with plus disease in at least 1 eye and 47 without
      plus disease. METHODS: Bedside noncontact SD-OCT imaging was performed after
      obtaining parental consent on 97 consecutive infants between January 2009 and
      September 2012. Fifty-seven subjects (31-49 weeks' post-menstrual age) who had an
      SD-OCT scan in at least 1 eye showing the edge of the optic nerve and at least 1
      major retinal vascular arcade were included. One eye per subject was randomly
      selected for analysis. Two masked graders evaluated scans for (1) retinal vessel
      elevation, (2) scalloped retinal layers, (3) hyporeflective vessels, and (4)
      retinal spaces. To coalesce the weight of these features, a Vascular Abnormality
      Score by OCT (VASO) was created. For quantitative assessment of vessel elevation,
      retinal surface maps were created. MAIN OUTCOME MEASURES: Prevalence of SD-OCT
      vascular abnormalities, the VASO, intergrader agreement, and presence of
      elevation on surface maps. RESULTS: From among 67 SD-OCT characteristics that
      were recorded, the most common characteristics found were vessel elevation (44%),
      hyporeflective vessels (40%), scalloped layers (22%), and retinal spaces (11%).
      Features significantly associated with plus disease were vessel elevation (P =
      0.01), hyporeflective vessels (P = 0.04), and scalloped retinal layers (P =
      0.006). Intragrader agreement was between 74% and 90% for all features. The VASO
      was significantly higher in subjects with plus disease (P = 0.0013). On 3
      dimensional SD-OCT volumes, eyes with plus disease had greater retinal surface
      elevation that more often matched en face retinal vascular patterns. CONCLUSIONS:
      We present a novel 3-dimensional analysis of vascular and perivascular
      abnormalities identified in SD-OCT images of eyes with ROP. The SD-OCT
      characteristics that are more common in eyes with plus disease provide the first
      in vivo demonstration of the effects of vascular dilation and tortuosity on
      perivascular tissue. The VASO and surface maps also delineate the severity of
      vascular pathology in plus disease. Further studies evaluating these findings in
      eyes with pre-plus versus normal posterior pole vessels may determine the
      usefulness of SD-OCT in the early detection of vascular abnormalities in ROP.

PMID- 24461544
TI  - Gold nanoprobes for multi loci assessment of multi-drug resistant tuberculosis.
AB  - Tuberculosis, still one of the leading human infectious diseases, reported 8.7
      million new cases in 2011 alone. Also, the increasing rate of multidrug-resistant
      tuberculosis (MDRTB) and its treatment difficulties pose a serious public health
      threat especially in developing countries. Resistance to isoniazid and
      rifampicin, first line antibiotics, is commonly associated with point mutations
      in katG, inhA and rpoB genes of Mycobacterium tuberculosis complex (MTBC).
      Therefore, the development of cheap, fast and simple molecular methods to assess
      susceptibility profiles would have a huge impact in the capacity of early
      diagnosis and treatment of MDRTB. Gold nanoparticles functionalized with thiol
      modified oligonucleotides (Au-nanoprobes) have shown the potential to provide a
      rapid and sensitive detection method for MTBC and single base mutations
      associated with antibiotic resistance, namely the characterization of the three
      most relevant codons in rpoB gene associated to rifampicin resistance. Here we
      extend the Au-nanoprobe approach towards discriminating specific mutations within
      inhA and rpoB genes in PCR amplified DNA from isolates. Using a multiplex PCR
      reaction for these two genes, it is possible to assess both loci in parallel, and
      extend the potential of the Au-nanoprobe method to MDRTB molecular
      characterization with special application in the most frequent Portuguese
      genotypes. 

PMID- 24461545
TI  - Effect of diabetes on treatment outcome of smear-positive pulmonary tuberculosis-
      a report from South India.
AB  - AIM: To assess the effect of diabetes on tuberculosis (TB) treatment outcome and
      sputum conversion among new smear-positive (NSP) cases registered under Directly
      Observed Treatment Short Course in South India. METHODS: Details on sputum
      conversion and TB treatment outcome were collected from case records of NSP cases
      (N = 332; M/F 247:85) registered at TB units of three districts in Tamil Nadu.
      Subjects were screened for diabetes and categorized as diabetic (TBDM) (n = 96;
      73:23) and non-diabetic (TBnonDM) (n = 149; 109:40). RESULTS: Among 245 selected
      TB patients, 93.5% were cured, 1.6% completed TB treatment, 2% had TB treatment
      failure (TF), and 0.4% had treatment default (TD), 0.4% with MDR-TB and 2% death
      rate. At the end of intensive phase of TB treatment, 14.7% remained sputum
      positive in the TBDM group, whereas it was 3.5% in the TBnonDM group. Mean
      duration (days) for sputum conversion was higher in the TBDM group (64.2 +/-
      10.5) compared to the TBnonDM group (61.5 +/- 7.5) (p<0.001). TF rate was higher
      (4.2% vs 0.7%) and MDR-TB (1%) was also seen in the TBDM group. No death and TD
      were seen among DM whereas it was 3.4 and 0.7% in TBnonDM. CONCLUSIONS: Delayed
      sputum conversion and high TB treatment failure rates were common in NSP cases
      with diabetes.

PMID- 24461548
TI  - Maggots, jawbones, and a multilingual archive of decay.

PMID- 24461546
TI  - Serum uric acid and insulin sensitivity in adolescents and adults with and
      without type 1 diabetes.
AB  - HYPOTHESIS: Decreased insulin sensitivity (IS) exists in type 1 diabetes. Serum
      uric acid (SUA), whose concentration is related to renal clearance, predicts
      vascular complications in type 1 diabetes. SUA is also inversely associated with
      IS in non-diabetics, but has not been examined in type 1 diabetes. We
      hypothesized SUA would be associated with reduced IS in adolescents and adults
      with type 1 diabetes. METHODS: The cross-sectional and longitudinal associations
      of SUA with IS were investigated in 254 adolescents with type 1 diabetes and 70
      without in the Determinants of Macrovascular Disease in Adolescents with Type 1
      Diabetes Study, and in 471 adults with type 1 diabetes and 571 without in the
      Coronary Artery Calcification in Type 1 diabetes (CACTI) study. RESULTS: SUA was
      lower in subjects with type 1 diabetes (p<0.0001), but still remained inversely
      associated with IS after multivariable adjustments in adolescents (beta+/-SE: 
      1.99+/-0.62, p=0.001, R2 =2%) and adults (beta+/-SE: -0.91+/-0.33, p=0.006, R2 =
      6%) with type 1 diabetes, though less strongly than in non-diabetic controls
      (adolescents: beta+/-SE: -2.70+/-1.19, p=0.03, R2 = 15%, adults: beta+/-SE: 
      5.99+/-0.75, p<0.0001, R2 =39%). CONCLUSION: We demonstrated a significantly
      weaker relationship between SUA and reduced IS in subjects with type 1 diabetes
      than non-diabetic controls.

PMID- 24461549
TI  - Even "unconscious thought" is influenced by attentional mechanisms.
AB  - In this commentary, we focus on the role of attentional mechanisms in unconscious
      thought. We argue that even distracted or unconscious thought is capacity limited
      and differences in scope of attention influence processing during unconscious
      thought. Attention also would influence processes at different stages in the
      proposed lens model. We conclude that there is a clear need to understand the
      role of attention to better understand conscious or unconscious thought. 

PMID- 24461547
TI  - The influence of sex on cardiovascular outcomes associated with diabetes among
      older black and white adults.
AB  - AIMS: It is unknown whether sex differences in the association of diabetes with
      cardiovascular outcomes vary by race. We examined sex differences in the
      associations of diabetes with incident congestive heart failure (CHF) and
      coronary heart disease (CHD) between older black and white adults. METHODS: We
      analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort
      study of community-dwelling individuals aged >=65 from four US counties. We
      included 4817 participants (476 black women, 279 black men, 2447 white women and
      1625 white men). We estimated event rates and multivariate-adjusted hazard ratios
      for incident CHF, CHD, and all-cause mortality by Cox regression and competing
      risk analyses. RESULTS: Over a median follow-up of 12.5years, diabetes was more
      strongly associated with CHF among black women (HR, 2.42 [95% CI, 1.70-3.40])
      than black men (1.39 [0.83-2.34]); this finding did not reach statistical
      significance (P for interaction=0.08). Female sex conferred a higher risk for a
      composite outcome of CHF and CHD among black participants (2.44 [1.82-3.26]) vs.
      (1.44 [0.97-2.12]), P for interaction=0.03). There were no significant sex
      differences in the HRs associated with diabetes for CHF among whites, or for CHD
      or all-cause mortality among blacks or whites. The three-way interaction between
      sex, race, and diabetes on risk of cardiovascular outcomes was not significant
      (P=0.07). CONCLUSIONS: Overall, sex did not modify the cardiovascular risk
      associated with diabetes among older black or white adults. However, our results
      suggest that a possible sex interaction among older blacks merits further study.

PMID- 24461550
TI  - Tylosin susceptibility of Staphylococci from bovine mastitis.
AB  - Although the 16-membered macrolide tylosin is commonly used for the treatment of
      bovine mastitis, little information is currently available about the
      susceptibility of mastitis pathogens to tylosin. In the present study, 112
      Staphylococcus aureus and 110 coagulase-negative Staphylococcus (CoNS) spp.
      isolates from cases of bovine mastitis were tested by broth microdilution and
      agar disk diffusion with 30 MUg tylosin disks. Susceptibility to erythromycin was
      tested by broth microdilution and disk diffusion using 15 MUg disks. Both test
      populations showed bimodal distributions of minimal inhibitory concentrations
      (MICs) and zone diameters with eleven S. aureus and eight CoNS isolates showing
      tylosin MICs of >= 256 MUg/ml and no zones of growth inhibition around the
      tylosin 30 MUg disks. All 19 isolates with tylosin MICs of >= 256 MUg/ml were
      also resistant to erythromycin. For six additional erythromycin-resistant
      isolates, tylosin MICs of 1-8 MUg/ml were observed. One S. aureus and two CoNS
      isolates showed inducible macrolide resistance. PCR analysis of the 25
      erythromycin-resistant staphylococcal isolates identified the resistance genes
      erm(A), erm(B), erm(C), erm(T), mph(C) and msr(A) alone or in different
      combinations. An excellent correlation between the results of the different
      tylosin susceptibility tests (broth microdilution versus disk diffusion) was seen
      for S. aureus and CoNS isolates. Since tylosin does not induce the expression of
      the aforementioned erm genes, isolates with an inducible resistance phenotype may
      - if only tylosin is tested - be falsely classified as tylosin-susceptible. Thus,
      erythromycin should be tested in parallel and tylosin should only be used for the
      treatment of infections caused by erythromycin-susceptible staphylococci.

PMID- 24461552
TI  - T-bar reconstruction of constricted ears and a new classification.
AB  - For the correction of constricted ears, many techniques are described in the
      literature, the majority based on Tanzer's classification of 1975. The
      improvements in ear reconstruction published by Brent, Nagata, Firmin and Park
      make better outcomes possible. It is therefore that a new classification for
      constricted ears is proposed, together with an alternative technique for
      correction of group IIA and IIB deformities, using a T-strut of costal cartilage
      to reconstruct the underdeveloped or missing superior crus of the antihelix. 

PMID- 24461551
TI  - Spread of new variant RHDV in domestic rabbits on the Iberian Peninsula.
AB  - Rabbit hemorrhagic disease outbreaks in young rabbits have been recently observed
      in Spain. In this study we have tracked the spread of variant RHDV in samples
      collected from rabbit farms over a period of more than one year using RT-PCR and
      antigen-capture ELISA. The isolates were sequenced and compared to classic and
      variant RHDV strains and phylogenetic analyses were conducted. Mortalities have
      been observed in kits as young as 11 days. More than 50% of the dead rabbits had
      been previously vaccinated against RHDV using commercially available inactivated
      vaccines indicating a putative lack of protection against the variant RHDV. The
      large majority of the studied outbreaks (94.5%) in Spanish farms during 2012 were
      due to variant RHDV and only 3 out of the 55 farms were affected by classic RHDV.
      The data demonstrates that the variant RHDV has spread through a large number of
      Spanish provinces in a relatively short period of time, largely replacing the
      previously predominant G1 RHDV genotypes. Considering the lack of efficient
      vaccines against the variant RHDV strains strict disease control and greater
      vigilance measures should be put in place. 

PMID- 24461553
TI  - Alar rotation flap for full thickness medial alar defects.

PMID- 24461555
TI  - Experimental study of the influence of the counter and scintillator on the
      universal curves in the cross-efficiency method in LSC.
AB  - The cross-efficiency method in LSC is one of the approaches proposed for the
      extension of the Systeme International de Reference (SIR) to radionuclides
      emitting no gamma radiation. This method is based on a so-called "universal cross
      efficiency curve", establishing a relationship between the detection efficiency
      of the radionuclide to be measured and the detection efficiency of a suitable
      tracer. This paper reports a study at LNHB on the influence of the scintillator
      and of the LS counter on the cross-efficiency curves. This was done by measuring
      the cross-efficiency curves obtained for (63)Ni and (55)Fe vs. (3)H, using three
      different commercial LS counters (Guardian 1414, Tricarb 3170 and Quantulus
      1220), three different liquid scintillator cocktails (Ultima Gold, Hionic Fluor
      and PicoFluor 15 from Perkin Elmer((r))), and for chemical and colour-quenched
      sources. This study shows that these cross-efficiency curves are dependent on the
      scintillator, on the counter used and on the nature of the quenching phenomenon,
      and thus cannot definitively be considered as "universal". 

PMID- 24461554
TI  - Severe renal impairment during triple therapy with telaprevir.

PMID- 24461556
TI  - Application of a Bonner sphere spectrometer for the determination of the angular
      neutron energy spectrum of an accelerator-based BNCT facility.
AB  - Experimental activities are underway at INFN Legnaro National Laboratories (LNL)
      (Padua, Italy) and Pisa University aimed at angular-dependent neutron energy
      spectra measurements produced by the (9)Be(p,xn) reaction, under a 5MeV proton
      beam. This work has been performed in the framework of INFN TRASCO-BNCT project.
      Bonner Sphere Spectrometer (BSS), based on (6)LiI (Eu) scintillator, was used
      with the shadow-cone technique. Proper unfolding codes, coupled to BSS response
      function calculated by Monte Carlo code, were finally used. The main results are
      reported here. 

PMID- 24461557
TI  - Newell and Shanks' approach to psychology is a dead end.
AB  - Newell & Shanks (N&S) criticize theories on decision making that include
      unconscious processes. To the extent that their own perspective becomes apparent,
      however, it is dated, implausible, and at odds with the major developments of the
      past decades. Their conclusions are, at least for research areas we feel entitled
      to evaluate, based on a biased sampling of the literature. 

PMID- 24461559
TI  - Radiological imaging of florid intravascular papillary endothelial hyperplasia in
      the mandibule: case report and literature review.
AB  - Intravascular papillary endothelial hyperplasia was a rare benign vascular
      proliferative process as a result of papillary proliferation of the endothelial
      cells within the vessels. To our knowledge, we reported the second case occurring
      in the madibule, and the first reported in 1984 in the literature. We discussed
      manifestations of multislice computed tomography and panoramic radiography about
      the lesion and relevant literature was reviewed. 

PMID- 24461558
TI  - Biomechanical analysis of impending femoral neck fractures: the role of
      percutaneous cement augmentation for osteolytic lesions.
AB  - BACKGROUND: Management of impending pathologic femoral neck fractures includes
      internal fixation, arthroplasty and megaprostheses. The study aim was to
      determine the augmentative effect of cement injection for minimally invasive
      treatment of femoral neck lesions. METHODS: Twenty-seven cadaveric femora
      received a simulated osteolytic lesion previously shown to decrease the femur's
      failure load by 50%. Specimens were allocated to three groups of nine and loaded
      to failure in simulated single-leg stance: (1) percutaneous cementation +
      internal fixation (PCIF); (2) percutaneous cementation (PC); and (3) internal
      fixation (IF). Lesion-only and augmented finite element models were virtually
      loaded and stresses were queried adjacent to the lesion. FINDINGS: PCIF resulted
      in the largest failure load though the increase was not significantly greater
      than the PC or IF groups. Inspection of the PC and PCIF specimens indicated that
      the generation of a cement column that spanned the superior and inferior cortices
      of the femoral neck increased failure loads significantly. Finite element
      analysis indicated that IF and PCIF constructs decreased the stress adjacent to
      the lesion to intact femur levels. Cementation without superior-to-inferior
      femoral neck cortical contact did not restore proximal femoral stress toward the
      intact condition. INTERPRETATION: Internal fixation alone and internal fixation
      with or without cementation produce similar levels of mechanical augmentation in
      femora containing a high-risk lesion of impending fracture. A cement injection
      technique that produces a cement column contacting the superior and inferior
      femoral neck cortices confers the highest degree of biomechanical stability,
      should percutaneous cementation alone be performed.

PMID- 24461560
TI  - Background uptake of breast-specific gamma imaging: correlation with mammographic
      breast density and background enhancement of breast MRI.
AB  - PURPOSE: To investigate the relationship between background uptake of breast
      specific gamma imaging (BSGI) mammographic breast density and background
      enhancement of breast magnetic resonance imaging (MRI). MATERIALS AND METHODS:
      The level and texture of background uptake of BSGI, mammographic breast density,
      and background enhancement of breast MRI are retrospectively reviewed in 104
      patients. RESULTS: Heterogeneous and increased background uptake of BSGI was
      significantly correlated with high mammographic breast density (P=.016, P=.001)
      and increased background enhancement of breast MRI (P=.015, P=.017). CONCLUSION:
      Interpreting BSGI of women showing high mammographic breast density or background
      enhancement of breast MRI needs to be carried out with caution.

PMID- 24461561
TI  - Ionic liquid mediated synthesis of mono- and bis-spirooxindole
      hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking
      studies.
AB  - One pot, three-component reaction of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4
      ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to
      mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized
      piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis
      spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase
      (AChE) with IC50 values of 2.36-9.43 MUM. For butyrylcholinesterase (BChE), mono
      cycloadducts in series 8 with IC50 values of lower than 10 MUM displayed better
      inhibitory activities than their bis-cycloadduct analogs in series 9 with IC50
      values of 7.44-19.12 MUM. The cycloadducts 9j and 8e were found to be the most
      potent AChE and BChE inhibitors with IC50 values of 2.35 and 3.21 MUM,
      respectively. Compound 9j was found to be competitive inhibitor of AChE while
      compound 8e was a mixed-mode inhibitor of BChE with calculated Ki values of 2.01
      and 6.76 MUM, respectively. Molecular docking on Torpedo californica AChE and
      human BChE showed good correlation between IC50 values and free binding energy
      values of the synthesized compounds docked into the active site of the enzymes.

PMID- 24461564
TI  - Preventing or masking psychosis? Possible unintended consequences of the ultra
      high-risk strategy.

PMID- 24461562
TI  - Synthesis of a C-phosphonate mimic of maltose-1-phosphate and inhibition studies
      on Mycobacterium tuberculosis GlgE.
AB  - The emergence of extensively drug-resistant tuberculosis (XDR-TB) necessitates
      the need to identify new anti-tuberculosis drug targets as well as to better
      understand essential biosynthetic pathways. GlgE is a Mycobacterium tuberculosis
      (Mtb) encoded maltosyltransferase involved in alpha-glucan biosynthesis. Deletion
      of GlgE in Mtb results in the accumulation of M1P within cells leading to rapid
      death of the organism. To inhibit GlgE a maltose-C-phosphonate (MCP) 13 was
      designed to act as an isosteric non-hydrolysable mimic of M1P. MCP 13, the only
      known inhibitor of Mtb GlgE, was successfully synthesized using a Wittig
      olefination as a key step in transforming maltose to the desired product. MCP 13
      inhibited Mtb GlgE with an IC50=230 +/- 24 MUM determined using a coupled enzyme
      assay which measures orthophosphate release. The requirement of M1P for the assay
      necessitated the development of an expedited synthetic route to M1P from an
      intermediate used in the MCP 13 synthesis. In conclusion, we designed a substrate
      analogue of M1P that is the first to exhibit Mtb GlgE inhibition.

PMID- 24461563
TI  - Measuring community functioning in schizophrenia with the Social Behaviour
      Schedule.
AB  - BACKGROUND: Current emphasis on community integration requires reliable and valid
      measures of social behaviour; existing assessments largely overlap with symptoms
      or provide little detail on functioning. This study aims to re-assess the Social
      Behaviour Schedule (SBS) to fulfil this measurement role. METHODS: Internal
      consistency, construct validity and test-retest reliability were investigated in
      421 community out-patients with schizophrenia. Concurrent validity was assessed
      against the Life Skill Profile (LSP), in 143 additional patients. RESULTS: A 17
      item SBS supported the construct validity of four factors: Antisocial Behaviour,
      Depressed Behaviour, Social Withdrawal and Thought Disturbance. It showed good
      test-retest reliability and rated significant social behaviour in a community
      sample. Weak correlations were observed with positive and negative symptoms. With
      the exception of Depressed Behaviour, the SBS factors showed strong correlations
      with the LSP. CONCLUSION: SBS-17 is a valid measure assessing relevant community
      social functioning factors with relatively few items. The SBS could be useful
      both in research and in clinical settings.

PMID- 24461565
TI  - Correlations of apathy and depression with postural instability in Parkinson
      disease.
AB  - BACKGROUND: Postural instability (PI) in Parkinson's disease (PD) is associated
      with depression and apathy based on UPDRS scores. We sought to examine the link
      using more objective PI measures. METHODS: Demographic, clinical, depression and
      apathy data were recorded for PD patients prospectively recruited from an
      outpatient university movement disorders clinic. PI was objectively evaluated
      using the standing center of pressure sway area. RESULTS: Thirty-seven PD
      patients participated in the study. Bivariate analysis revealed that PI was
      significantly correlated to both apathy (p=0.018) and depression (p=0.014).
      Hierarchical regression revealed that apathy significantly predicted PI but
      depression did not significantly add to the prediction. Also, depression did not
      significantly predict PI and the addition of apathy did not increase this
      prediction. CONCLUSION: Apathy and depression are both associated with objective
      measures of PI, and apathy appears a stronger predictor of PI than depression.
      Concomitant improvement in PI may be important to consider when measuring apathy
      or depression interventions in PD.

PMID- 24461566
TI  - Varicella-zoster virus vasculopathy. A review description of a new case with
      multifocal brain hemorrhage.
AB  - BACKGROUND: The varicella zoster virus (VZV) is a highly neurotropic virus that,
      after the primary infection, remains latent in the nerve cells and can reactivate
      many years later, resulting in various conditions affecting the central nervous
      system, such as vasculopathy and stroke. METHODS: We report on a review of the
      published literature that included all case reports identified via PubMed and an
      additional unpublished case of VZV vasculopathy. All epidemiological, clinical,
      laboratory, imaging, virologic, treatment and outcome data collected are
      described. RESULTS: Of the 62 patients, 41.6% were immunocompromised. Ischemic
      stroke occurred in 77.2% of the patients, comprising cases of isolated (37.1%)
      and multifocal stroke (17.7%). Multifocal, ischemic and hemorrhagic stroke was
      only described in the newly reported case. The magnetic resonance imaging results
      were normal in 2.9% of the cases. The vascular studies (angiography and magnetic
      resonance angiography [MRA]) revealed signs of angiitis in 74.4% of the cases;
      the small arteries were involved in 38.5% of the cases, large arteries in 17.7%
      and mixed in 43.5%. For 95.2% of the patients, the cerebrospinal fluid (CSF) was
      positive for VZV IgG antibodies, and for 46.1% of the patients, the CSF was
      positive for polymerase chain reaction (PCR); however, the diagnosis was
      confirmed in only 3 of 6 biopsies. DISCUSSION: VZV vasculopathy can occur in both
      immunocompetent and immunosuppressed patients. Neuroimaging can reveal stroke and
      angiitis, and the detection of VZV-specific IgG antibodies in the CSF is a
      reliable and highly sensitive diagnostic tool. The multifocal nature of VZV
      vasculopathy makes biopsy a test with low sensitivity and high morbidity.

PMID- 24461567
TI  - Recovery and outcome of frontal alien hand syndrome after anterior cerebral
      artery stroke.
AB  - Ischemic lesions within the territory of the anterior cerebral artery present
      with a variety of clinical signs and symptoms. Among these, frontal alien hand
      syndrome is rare and easily overlooked in the acute clinical setting, but
      significantly impacts on functional activities of daily life. Given its rareness,
      very little is known about its long-term outcome. To shade some more light onto
      this issue, clinical presentation, course of rehabilitation and outcome of two
      illustrative cases of frontal alien hand syndrome following anterior cerebral
      artery stroke are presented. Within seven and nine months from symptom onset,
      respectively, the clinical symptoms of frontal alien hand had resolved completely
      in both cases. We conclude that frontal alien hand syndrome has a favourable long
      term outcome. 

PMID- 24461568
TI  - "Caring for insiderness": phenomenologically informed insights that can guide
      practice.
AB  - Understanding the "insider" perspective has been a pivotal strength of
      qualitative research. Further than this, within the more applied fields in which
      the human activity of "caring" takes place, such understanding of "what it is
      like" for people from within their lifeworlds has also been acknowledged as the
      foundational starting point in order for "care" to be caring. But we believe that
      more attention needs to be paid to this foundational generic phenomenon: what it
      means to understand the "insiderness" of another, but more importantly, how to
      act on this in caring ways. We call this human phenomenon "caring for
      insiderness." Drawing on existing phenomenological studies of marginal caring
      situations at the limits of caring capability, and through a process of
      phenomenologically oriented reflection, we interrogated some existential themes
      implicit in these publications that could lead to deeper insights for both
      theoretical and applied purposes. The paper provides direction for practices of
      caring by highlighting some dangers as well as some remedies along this path. 

PMID- 24461569
TI  - Life interrupted and life regained? Coping with stroke at a young age.
AB  - Stroke is a leading cause of disability across the developed world, affecting an
      increasing number of younger people. In this article, we seek to understand the
      experience of stroke as a disabling life situation among young people and the
      strategies that they use to recover and cope. Directed content analysis was
      conducted from interviews with 17 community-dwelling stroke survivors aged 55
      years and younger across the United Kingdom. The sample was drawn from a larger
      maximum variation sample of stroke survivors. Using the sociological concepts of
      biographical disruption and biographical repair as a guide, excerpts from the
      interviews pertaining to aspects of the patients' life that were interrupted, in
      addition to how they coped with the changes, were selected and analysed. All
      individuals described an "altered sense of self," a theme that included loss of
      identity, family disruption, and/or loss of valued activities. Individuals sought
      to adapt their sense of self by seeking external support, by restoring normality,
      and/or through positive reflection. Despite the adapted self that emerged, most
      individuals continued to experience impairments. While young stroke survivors
      adapt to their illness over time, they continue to experience impairments and
      disruptions in their personal and work lives. A holistic model of rehabilitation
      that helps individuals regain the capacity for everyday activities related to
      work, family life, and leisure can begin to address the emotional ramifications
      of diseases such as stroke, restore wellness, and work towards minimizing the
      burden felt by family caregivers and children. 

PMID- 24461571
TI  - The impact of cesarean section on neonatal outcome of infants born at 23weeks of
      gestation.
AB  - OBJECTIVE: Determine the impact of cesarean section (CS) on neonatal outcome of
      infants born at 23weeks of gestation. METHODS: A retrospective study was
      performed involving 34 infants born at 23weeks and 91 infants born at 24-26weeks.
      Indications necessitating delivery were severe pregnancy induced hypertension,
      non-reassuring fetal heart rate patterns (NRFHRs), or intrauterine infection
      (IUI). Obstetrical indication for CS included NRFHR and breech presentation. Poor
      outcome included neonatal death or cerebral palsy. Univariate and multiple
      logistic analyses were performed to determine the effect of CS for obstetrical
      indications on poor outcome. RESULTS: The incidence of poor outcome was
      significantly higher at 23weeks (number of poor outcomes/total number: 22/34)
      compared to that (31/91) at 24-26weeks (p<0.01). The incidence of a poor outcome
      was significantly higher at 23weeks for infants having NRFHR (11/16) compared to
      those at 24-26weeks (15/43, p=0.02). However, the incidence of a poor outcome was
      similar in infants with IUI (6/10 at 23weeks versus 5/11 at 24-26weeks, p=0.41).
      Vaginal birth in cases of obstetrical indication for CS at 23weeks was associated
      with higher risk of a poor outcome (odds ratio: 8.2). In contrast, the risk at 24
      26weeks was not higher (OR, 0.8). After adjustment using variables of vaginal
      birth and IUI, vaginal birth significantly affected poor outcome (OR, 13.0).
      CONCLUSION: Poor neonatal outcome was closely related to the mode of delivery,
      suggesting that CS for obstetrical indication at 23weeks may improve neonatal
      outcome.

PMID- 24461570
TI  - Perspectives on quality mental health care from Brazilian and Cape Verdean
      outpatients: implications for effective patient-centered policies and models of
      care.
AB  - Mental health providers are increasingly coming into contact with large and
      growing multi-racial/ethnic and immigrant patient populations in the United
      States. Knowledge of patient perspectives on what constitutes quality mental
      health care is necessary for these providers. The aim of this study was to
      identify indicators of quality of mental health care that matter most to two
      underrepresented immigrant patient groups of Portuguese background: Brazilians
      and Cape Verdeans. A qualitative design was adopted using focus group
      discussions. Six focus groups of patients (n=24 Brazilians; n=24 Cape Verdeans)
      who received outpatient mental health treatment through public safety net clinics
      in the northeast region of the United States were conducted. The Consensual
      Qualitative Research analytic method allowed us to identify three quality of care
      domains: provider performance, aspects of mental health care environment, and
      effectiveness of mental health care treatment. Provider performance was
      associated with five categories: relational, communication, linguistic, cultural,
      and technical competencies. Aspects of mental health care environment were linked
      to two categories: psychosocial and physical environment. Effectiveness of mental
      health care treatment was related to two categories: therapeutic relationship and
      treatment outcomes. Study findings provide useful data for the development of
      more culturally appropriate and effective patient-centered models and policies in
      mental health care. 

PMID- 24461572
TI  - Effects of pre-feeding oral stimulation on oral feeding in preterm infants: a
      randomized clinical trial.
AB  - OBJECTIVE: To evaluate the effect of early oral stimulation before the
      introduction of oral feeding, over the duration of concomitant tube feeding
      ("transition period"), the length of hospital stay and the breastfeeding rates
      upon discharge in preterm infants. STUDY DESIGN: Preterm infants born between 26
      and 33 weeks gestational age (n=86), were randomized into an intervention and
      control group. Infants in the intervention group received an oral stimulation
      program consisting in stimulation of the oral structures for 15 min at least for
      10 days, before introduction of oral feeding. Oral feeding was introduced at 34
      weeks GA in both groups. RESULTS: Breastfeeding rates upon discharge were
      significantly higher in the intervention than in the control group (70% versus
      45.6%, p=0.02). There was no statistical difference between the two groups in
      terms of the length of the transition period or the length of the hospital stay.
      The need for prolonged CPAP support (HR=0.937, p=0.030) and small size for
      gestational age at birth (HR=0.338, p=0.016) were shown to be risk factors for a
      prolonged transition period. CONCLUSION: A pre-feeding oral stimulation program
      improves breastfeeding rates in preterm infants. The study results suggest that
      oral stimulation, as used in our specific population, does not shorten the
      transition period to full oral feeding neither the length of hospital stay.

PMID- 24461573
TI  - New evidence for teriflunomide in multiple sclerosis.

PMID- 24461575
TI  - Image segmentation methods for intracranial aneurysm haemodynamic research.
AB  - Patient-specific haemodynamic technology is being increasingly utilised in
      clinical applications. Under normal circumstances, computational haemodynamic
      simulation is performed using geometric results obtained via medical image
      segmentation. However, even when employed upon the same set of medical imaging
      data, both the geometry and volume of intracranial aneurysm models are highly
      dependent upon varying insufficiently validated vascular segmentation methods. In
      this study, we compared three segmentation methods to segment the geometry of the
      aneurysm. These include: the Region Growing Threshold (RGT), Chan-Vese model (CV)
      and Threshold-Based Level Set (TLS). The results obtained were evaluated via
      measurement of arterial volume differences (VD), local geometric shapes, and
      haemodynamic simulation results. In total, 45 patient-specific aneurysm cases
      with three different anatomy locations were assessed in this study. From this, we
      discovered that the average VD of all three segmentation methods lay in the
      vicinity of 9.3% (SD= +/- 4.6%). The computational haemodynamic simulation was
      performed via the use of the vessel geometries. Analyses produced an average of
      23.2% (SD= +/- 8.7%) difference in energy loss (EL) between the varying
      segmentation methods, with the difference in Wall Shear Stress (WSS) averaging
      24.0% (SD= +/- 8.5%) and 126.4% (SD= +/- 124.4%) for the highest and lowest
      volumes of WSS respectively. The results of the lowest WSS, was seen to be
      significantly dependent upon the geometry of the aneurysm surface. It is
      therefore essential, in order to confirm the quality of segmentation processes in
      the application of patient-specific analyses of cerebrovascular haemodynamics -
      to validate these individual segmentation methods.

PMID- 24461577
TI  - Granulomatous appendicitis: An uncommon cause of acute abdomen.

PMID- 24461576
TI  - Healthy older adults have insufficient hip range of motion and plantar flexor
      strength to walk like healthy young adults.
AB  - Limited plantar flexor strength and hip extension range of motion (ROM) in older
      adults are believed to underlie common age-related differences in gait. However,
      no studies of age-related differences in gait have quantified the percentage of
      strength and ROM used during gait. We examined peak hip angles, hip torques and
      plantar flexor torques, and corresponding estimates of functional capacity
      utilized (FCU), which we define as the percentage of available strength or joint
      ROM used, in 10 young and 10 older healthy adults walking under self-selected and
      controlled (slow and fast) conditions. Older adults walked with about 30% smaller
      hip extension angle, 28% larger hip flexion angle, 34% more hip extensor torque
      in the slow condition, and 12% less plantar flexor torque in the fast condition
      than young adults. Older adults had higher FCU than young adults for hip flexion
      angle (47% vs. 34%) and hip extensor torque (48% vs. 27%). FCUs for plantar
      flexor torque (both age groups) and hip extension angle (older adults in all
      conditions; young adults in self-selected gait) were not significantly <100%, and
      were higher than for other measures examined. Older adults lacked sufficient hip
      extension ROM to walk with a hip extension angle as large as that of young
      adults. Similarly, in the fast gait condition older adults lacked the strength to
      match the plantar flexor torque produced by young adults. This supports the
      hypothesis that hip extension ROM and plantar flexor strength are limiting
      factors in gait and contribute to age-related differences in gait. 

PMID- 24461578
TI  - Editorial comment.

PMID- 24461579
TI  - Morphology of accessory genital glands of spotted paca (Agouti paca Linnaeus,
      1766).
AB  - The spotted paca is the second largest rodent in Brazil, where it is of great
      economic interest in impoverished regions in view of its prominence as a low-cost
      source of protein. Little is known about the morphology of the accessory genital
      glands of this species. Thus, we studied the position and morphology of the
      genitals in ten adult male spotted pacas. The animals were divided into two
      groups, five animals were used for fixing of samples in 10% aqueous formaldehyde
      for macroscopic studies and the other five animals were designated for
      microscopic analysis. These were arranged in pairs and had the vesicular,
      prostate, coagulating and bulbourethral glands identified, being structured as
      mucous glands, which lead into the pelvic urethra. It was concluded that the
      accessory genital glands found in the paca are the same as those found in most
      rodents, showing similar histological aspects. 

PMID- 24461580
TI  - Effect of estradiol cypionate and amount of progesterone in the intravaginal
      device on synchronization of estrus, ovulation and on pregnancy rate in beef cows
      treated with FTAI based protocols.
AB  - Three experiments were conducted to evaluate the effect of estradiol cypionate
      (ECP) and amount of progesterone in the intravaginal device (PID) on
      synchronization of estrus and ovulation, follicular dynamics, luteal dynamics and
      function and on pregnancy rate in beef cows treated with fixed-time artificial
      insemination (FTAI) based protocols. In Experiment 1, we evaluated the
      synchronization of ovulation using 1mg of ECP at PID removal (day 8 after PID
      insertion) or 1mg of estradiol benzoate (EB) 24h later, in cows treated with
      0.558 or 1g of progesterone (P4). The final subgroups were: 0.558g+ECP: n=10;
      0.558g+EB: n=11; 1g+ECP: n=10; 1g+EB: n=10. Ovarian ultrasonic examinations were
      performed to detect the dominant follicle and ovulation. There was no effect of
      treatments on the diameter of dominant follicle at any time, and on the mean
      interval to estrus and to ovulation (P>0.05); however, ECP treated cows had
      scattered distribution of estrus (P<0.03) and ovulation (P<0.03). In Experiment
      2, cows received the following treatments: 0.558gP4+ECP: n=52; 0.558gP4+EB: n=52;
      1gP4+ECP: n=50; 1gP4+EB: n=52; and FTAI. Pregnancy rate did not differ (P>0.05)
      between progesterone content (0.558g: 52.9%, 55/104; 1g: 56.9%, 58/102) but
      differed between estradiol esters (P<0.05; ECP: 48.9%, 49/102; EB: 61.5%,
      64/104). In Experiment 3, cows received: 0.558gP4+ECP: n=55; 0.558gP4+EB: n=53;
      1gP4+ECP: n=54; 1gP4+EB: n=53; and FTAI. Pregnancy rate did not differ (P>0.05)
      between progesterone content (0.558g: 48.1%, 52/108; 1g: 53.3%, 57/107) and
      estradiol esters (ECP: 47.7%, 52/109; EB: 53.8%, 57/106). In conclusion, ECP
      administration at device removal and progesterone content of PID has no influence
      on the synchronization of estrus, follicular dynamics, luteal dynamics and
      function. However, ECP administration affected the synchronization of ovulation
      and pregnancy rate in non-suckling beef cows, but did not affected pregnancy rate
      in suckling beef cows. Future studies should evaluate the distribution of
      ovulations in suckling Bos taurus beef cows. 

PMID- 24461574
TI  - Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a
      randomised, double-blind, placebo-controlled, phase 3 trial.
AB  - BACKGROUND: Teriflunomide is an oral disease-modifying therapy approved for
      treatment of relapsing or relapsing-remitting multiple sclerosis. We aimed to
      provide further evidence for the safety and efficacy of teriflunomide in patients
      with relapsing multiple sclerosis. METHODS: This international, randomised,
      double-blind, placebo-controlled, phase 3 study enrolled adults aged 18-55 years
      with relapsing multiple sclerosis, one or more relapse in the previous 12 months
      or two or more in the previous 24 months but no relapse in the previous 30 days,
      and an Expanded Disability Status Scale (EDSS) score of 5.5 points or less.
      Patients were recruited from 189 sites in 26 countries and randomly assigned
      (1:1:1) to once-daily placebo, teriflunomide 7 mg, or teriflunomide 14 mg via an
      interactive voice recognition system. Treatment duration was variable, ending 48
      weeks after the last patient was included. The primary endpoint was annualised
      relapse rate (number of relapses per patient-year) and the key secondary endpoint
      was time to sustained accumulation of disability (an EDSS score increase of at
      least 1 EDSS point sustained for a minimum of 12 weeks), both analysed in the
      modified intention-to-treat population (all patients who received at least one
      dose of assigned study medication). This study is registered with
      ClinicalTrials.gov, number NCT00751881. FINDINGS: Between Sept 17, 2008, and Feb
      17, 2011, 1169 patients were randomly assigned to a treatment group, of whom 388,
      407, and 370 patients received at least one dose of placebo, teriflunomide 7 mg,
      or teriflunomide 14 mg, respectively. By the end of the study, the annualised
      relapse rate was higher in patients assigned to placebo (0.50 [95% CI 0.43-0.58])
      than in those assigned to teriflunomide 14 mg (0.32 [0.27-0.38]; p=0.0001) or
      teriflunomide 7 mg (0.39 [0.33-0.46]; p=0.0183). Compared with placebo,
      teriflunomide 14 mg reduced the risk of sustained accumulation of disability
      (hazard ratio [HR] 0.68 [95% CI 0.47-1.00]; log-rank p=0.0442); however,
      teriflunomide 7 mg had no effect on sustained accumulation of disability (HR 0.95
      [0.68-1.35]; log-rank p=0.7620). The most common adverse events were alanine
      aminotransferase increases (32 [8%] of 385 patients in the placebo group vs 46
      [11%] of 409 patients in the teriflunomide 7 mg group vs 52 [14%] of 371 patients
      in the teriflunomide 14 mg group), hair thinning (17 [4%] vs 42 [10%] vs 50
      [13%]), and headache (42 [11%] vs 60 [15%] vs 46 [12%]). Incidence of serious
      adverse events was similar in all treatment groups (47 [12%] vs 52 [13%] vs 44
      [12%]). Four deaths occurred, none of which was considered to be related to study
      drug (respiratory infection in the placebo group, traffic accident in the
      teriflunomide 7 mg group, and suicide and septicaemia due to Gram-negative
      infection complicated by disseminated intravascular coagulopathy in the
      teriflunomide 14 mg group). INTERPRETATION: Teriflunomide 14 mg was associated
      with a lower relapse rate and less disability accumulation compared with placebo,
      with a similar safety and tolerability profile to that reported in previous
      studies. These results confirm the dose effect reported in previous trials and
      support the use of teriflunomide 14 mg in patients with relapsing multiple
      sclerosis. FUNDING: Genzyme, a Sanofi company.

PMID- 24461581
TI  - Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell
      activation.
AB  - BACKGROUND: Mast cells have gained notoriety based on their detrimental
      contributions to IgE-mediated allergic disorders. Although mast cells express the
      vitamin D receptor (VDR), it is not clear to what extent 1alpha,25
      dihydroxyvitamin D3 (1alpha,25[OH]2D3) or its predominant inactive precursor
      metabolite in the circulation, 25-hydroxyvitamin D3 (25OHD3), can influence IgE
      mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo.
      OBJECTIVE: We sought to assess whether the vitamin D3 metabolites 25OHD3 and
      1alpha,25(OH)2D3 can repress IgE-dependent mast cell activation through mast cell
      25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) and mast cell-VDR activity.
      METHODS: We measured the extent of vitamin D3 suppression of IgE-mediated mast
      cell degranulation and mediator production in vitro, as well as the vitamin D3
      induced curtailment of PCA responses in WBB6F1-Kit(W/W-v) or C57BL/6J-Kit(W-sh/W
      sh) mice engrafted with mast cells that did or did not express VDR or CYP27B1.
      RESULTS: Here we show that mouse and human mast cells can convert 25OHD3 to
      1alpha,25(OH)2D3 through CYP27B1 activity and that both of these vitamin D3
      metabolites suppressed IgE-induced mast cell-derived proinflammatory and
      vasodilatory mediator production in a VDR-dependent manner in vitro. Furthermore,
      epicutaneously applied vitamin D3 metabolites significantly reduced the magnitude
      of skin swelling associated with IgE-mediated PCA reactions in vivo; a response
      that required functional mast cell-VDRs and mast cell-CYP27B1. CONCLUSION: Taken
      together, our findings provide a mechanistic explanation for the anti
      inflammatory effects of vitamin D3 on mast cell function by demonstrating that
      mast cells can actively metabolize 25OHD3 to dampen IgE-mediated mast cell
      activation in vitro and in vivo.

PMID- 24461582
TI  - Effects of selective COX-2 inhibition on allergen-induced bronchoconstriction and
      airway inflammation in asthma.
AB  - BACKGROUND: Prostaglandins that constrict and relax airways are synthesized in
      reactions catalyzed by either COX-1 or COX-2. It is not known whether selective
      inhibition of COX-2 makes asthmatic responses better or worse. OBJECTIVE: To
      determine the effects of the selective COX-2 inhibitor, etoricoxib, on allergen
      induced bronchoconstriction in asthmatic subjects. METHODS: Sixteen subjects with
      mild atopic asthma underwent rising dose inhalation challenges with allergen or
      methacholine to determine PD20 FEV1 during a control study period or after 10 to
      13 days of treatment with etoricoxib (90 mg once daily). The order of study
      periods was randomized with at least 2-week washout periods. Induced sputum cells
      and fractional exhaled nitric oxide levels were used to assess airway
      inflammation and blood assays for COX-1 and COX-2 activity to assess enzyme
      inhibition. Urinary excretion of lipids was used to assess prostaglandin
      biosynthesis. RESULTS: Etoricoxib did not change baseline lung function, nor
      airway responsiveness to allergen or to methacholine. Neither were the allergen
      induced increase in sputum eosinophils and fractional exhaled nitric oxide levels
      affected by treatment. The biochemical effectiveness of the treatment was
      established both in the blood assays and by the distinct inhibitory effect of
      etoricoxib on urinary excretion of tetranor-prostaglandin E2 (P < .001).
      CONCLUSIONS: This first study of COX-2 inhibition in provoked asthma found no
      negative effects of etoricoxib on allergen-induced airflow obstruction and sputum
      eosinophils, basal lung function, or methacholine responsiveness. The study
      suggests that short-term use of COX-2 inhibitors is safe in subjects with asthma.

PMID- 24461584
TI  - Author reply: To PMID 23622875.

PMID- 24461583
TI  - Early-life determinants of asthma from birth to age 20 years: a German birth
      cohort study.
AB  - BACKGROUND: The lack of longitudinal data analyses from birth to adulthood is
      hampering long-term asthma prevention strategies. OBJECTIVE: We aimed to
      determine early-life predictors of asthma incidence up to age 20 years in a birth
      cohort study by applying time-to-event analysis. METHODS: In 1990, the
      Multicenter Allergy Study included 1314 newborns in 5 German cities. Children
      were evaluated from birth to age 20 years at 19 time points. Using a Cox
      regression model, we examined the associations between 36 early-life factors and
      onset of asthma based on a doctor's diagnosis or asthma medication (primary
      outcome), typical asthma symptoms, or allergic asthma (including positive IgE
      measurements). RESULTS: Response at 20 years was 71.6%. Two hundred eighteen
      subjects met the primary outcome criteria within 16,257 person years observed.
      Asthma incidence was lower in participants who were vaccinated (measles, mumps,
      and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard
      ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was
      higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95%
      CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR,
      1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]),
      had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]),
      had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with
      asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were
      aspects of diet and breast-feeding, pet ownership, presence of older siblings,
      and passive smoking. CONCLUSION: Parental asthma and nasal allergy increase
      asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure
      during pregnancy, receiving vaccinations in early childhood, and starting day
      care between 1.5 and 3 years of age might prevent or delay the development of
      asthma.

PMID- 24461585
TI  - Quantitative measurement of interocular suppression in anisometropic amblyopia.

PMID- 24461587
TI  - Prevention of Frey syndrome with superficial temporal fascia interpositioning: a
      retrospective study.
AB  - Frey syndrome (FS) is a commonly documented postoperative complication following
      parotidectomy. The aim of this study was to clinically evaluate the efficacy of
      superficial temporal fascia (STF) as interpositioning barrier between the
      overlying skin flap and the parotid bed for the prevention of FS following
      superficial parotidectomy. A retrospective study was designed involving a
      population of patients from a single institution who underwent superficial
      parotidectomy for parotid tumours and refractory chronic sialadenitis from 2008
      to 2011. Forty-eight cases were identified and divided into two groups: group I
      (n=25) had undergone STF interpositioning between the skin flap and the parotid
      bed after extending the modified Blair's incision in the temporal region, and
      group II (n=23) had undergone a superficial parotidectomy using the modified
      Blair's incision without any interpositioning. In group I, one of 25 cases (4%)
      developed mild FS; in group II, nine of 23 cases (39.1%) developed FS of varying
      severity. There were no cases of permanent facial palsy in either group. Alopecia
      along the temporal extension of the incision line was imperceptible in all group
      I cases. The use of an STF interpositioning barrier between the overlying skin
      flap and the parotid bed is a safe and effective procedure for the prevention of
      FS following superficial parotidectomy. 

PMID- 24461586
TI  - The neovascular age-related macular degeneration database: multicenter study of
      92 976 ranibizumab injections: report 1: visual acuity.
AB  - PURPOSE: To study real-world ranibizumab therapy for treatment-naive eyes with
      neovascular age-related macular degeneration (nAMD) and to benchmark standards of
      care. DESIGN: Multicenter, national nAMD database study. PARTICIPANTS: A total of
      92 976 treatment episodes from 12 951 eyes of 11 135 patients. METHODS: Up to 5
      years of routinely collected, anonymized data were extracted remotely from 14
      United Kingdom centers to a central database using an electronic medical record
      (EMR) system. Participating centers used ranibizumab to treat nAMD using a
      loading phase of 3 monthly injections and a pro re nata retreatment regimen. The
      minimum data set defined before first patient data entry and mandated by the EMR
      system included age, Early Treatment Diabetic Retinopathy Study visual acuity
      (VA) at all visits, and injection episodes. MAIN OUTCOME MEASURES: Baseline VA,
      change in VA, number of treatments and clinic visits, and baseline
      characteristics affecting VA change. RESULTS: Information from more than 300 000
      clinic visits (2.8 million data points) were collated. Mean age at first
      treatment was 79.1 years, with a female preponderance of 1.7:1. Mean VA (letters)
      for eyes followed up for at least 3 years from a baseline of 55 letters was 57
      (+2) letters at 1 year, 56 (+1) letters at 2 years, and 53 (-2) letters at 3
      years. The proportion of eyes that avoided moderate vision loss at years 1, 2,
      and 3 were 90%, 84%, and 82%, respectively. The proportion of eyes with VA of
      20/40 or better were: baseline, 16%; year 1, 30%; year 2, 30%; and year 3, 29%.
      The median number of treatments for eyes followed up for at least 3 years in
      years 1, 2 and 3 was 5, 4, and 4, respectively, and the median number of
      outpatient visits was 9.2, 8.2, and 8.2, respectively. Baseline VA was related
      inversely to mean vision gain at 3 months. Older age was associated with lower
      presenting VA. CONCLUSIONS: Real-world visual outcomes achieved at a large number
      of centers across the United Kingdom do not match the results achieved in most
      randomized trials, but they were delivered with substantially fewer injections
      and hospital visits. This study provides important benchmark results that should
      be of interest to patients, retina specialists, and commissioners of health care.
      This study demonstrates the EMR system's potential usefulness for future phase 4
      and 5 clinical trials.

PMID- 24461588
TI  - The presumption of consciousness.
AB  - Throughout this article the authors presume - without justification - that
      decision making must be a conscious process unless proved otherwise, and they
      place an unreasonably strict burden of proof on anyone wishing to claim a role
      for unconscious processing. In addition, I show that their arguments do not, as
      implied here, impact upon contemporary dual-process theories of reasoning and
      decision making. 

PMID- 24461589
TI  - The role of central nervous system on hypoglycemia and the feasibility of the
      brain theory in traditional Chinese medicine on treatment of diabetes mellitus.
AB  - The central nervous system (CNS) plays a key regulatory role in glucose
      homeostasis. In particular, the brain is important in initiating and coordinating
      protective counterregulatory responses when blood glucose levels fall. This may
      due to the metabolic dependency of the CNS on glucose, and protection of food
      supply to the brain. In healthy subjects, blood glucose is normally maintained
      within a relatively narrow range. Hypoglycemia in diabetic patients can increase
      the risk of complications, such as heart disease and diabetic peripheral
      neuropathy. The clinical research finds that the use of traditional Chinese
      medicine (TCM) has a positive effect on the treatment of hypoglycemia. Here the
      authors reviewed the current understanding of sensing and counterregulatory
      responses to hypoglycemia, and discuss combining traditional Chinese and Western
      medicine and the theory of iatrogenic hypoglycemia in diabetes treatment.
      Furthermore, the authors clarify the feasibility of treating hypoglycemia on the
      basis of TCM theory and CNS and have an insight on its clinical practice. 

PMID- 24461590
TI  - Medicine prescription practices of homeopathic undergraduate students in West
      Bengal, India.
AB  - OBJECTIVE: To our knowledge, prescription of homeopathic medicines by homeopathic
      undergraduate students has not been studied before though it may possess serious
      implications. We aimed to determine the practice and attitudes of prescription by
      homeopathic undergraduate students. METHODS: A cross-sectional study was carried
      out involving all the students from four government homeopathic schools of West
      Bengal, India. Ethical requirements were ensured and data were collected using
      self-administered questionnaires. Chi-square tests and logistic univariate
      regression analyses were performed to identify associations and differences.
      RESULTS: A total of 328 forms were completed. Of these, 264 (80.5%) homeopathic
      undergraduate students admitted of prescribing medicines independently and most
      (40.5%) said that they did this 2-3 times a year. The most common reasons for
      this were 'urgency of the problem' (35.2%), 'previous experience with same kind
      of illness' (31.8%), and 'the problem too trivial to go to a doctor' (25.8%).
      About 63.4% of the students thought that it was alright to independently diagnose
      an illness while 51.2% thought that it was alright for them to prescribe
      medicines to others. Common conditions encountered were fever, indigestion, and
      injury. Students who prescribed medicines were more likely to belong to Calcutta
      Homeopathic Medical College and Hospital (odds ratio = 5.8; 95% confidence
      interval 2.247-14.972). Prescription by students gradually increased with
      academic years of homeopathic schools. Many students thought it was alright for
      students to diagnose and treat illnesses. CONCLUSION: Prescription of medicines
      by homeopathic undergraduate students is quite rampant and corrective measures
      are warranted.

PMID- 24461591
TI  - Developing the criteria for evaluating quality of individualization in
      homeopathic clinical trial reporting: a preliminary study.
AB  - OBJECTIVE: This study describes the development of a preliminary version of an
      instrument that attempts to assess the quality of reports of individualized
      homeopathic prescriptions in clinical trials and observational studies. METHODS:
      A multidisciplinary panel of 15 judges produced an initial version of the
      instrument through iterative Delphi rounds and pilot-tested the instrument on
      five clinical trials. Later they assessed, under blind conditions, the
      individualization quality of 40 randomly-selected research reports. The final
      version of the instrument included six criteria. These items were scored
      consistently by all the raters regardless of background. RESULTS: The instrument
      appeared to have adequate face and content validity, acceptable internal
      consistency or reliability (Cronbach's alpha 0.606 - 0.725), significant
      discriminant validity (F = 398.7; P < 0.000 1), moderate interrater reliability
      (Fleiss kappa 0.533), agreeable test-retest reliability (Cohen's kappa 0.765 -
      0.934), moderate sensitivity (0.4; 95% confidence interval 0.253-0.566), and high
      specificity (1.0; 95% confidence interval 0.891-1.000). CONCLUSION: The initial
      data suggest that this instrument may be a promising systematic tool amendable
      for further development.

PMID- 24461592
TI  - Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene
      expression in human cell lines in vitro and murine hepatocytes in vivo.
AB  - OBJECTIVE: In the present study, we systemically evaluated the ability of two
      bioactive compounds from traditional Chinese medicine, celastrol and pristimerin,
      to enhance recombinant adeno-associated virus (rAAV) serotype vector-mediated
      transgene expression both in human cell lines in vitro, and in murine hepatocytes
      in vivo. METHODS: Human cell lines were infected with rAAV vectors with either
      mock treatment or treatment with celastrol or pristimerin. The transgene
      expression, percentage of nuclear translocated viral genomes and the
      ubiquitination of intracellular proteins were investigated post-treatment. In
      addition, nonobese diabetic/severe combined immunodeficient gamma (NSG) mice were
      tail vain-injected with rAAV vectors and co-administered with either dimethyl
      sulfoxide, celastrol, pristimerin or a positive control, bortezomib. The
      transgene expression in liver was detected and compared over time. RESULTS: We
      observed that treatment with pristimerin, at as low as 1 MUmol/L concentration,
      significantly enhanced rAAV2 vector-mediated transgene expression in vitro, and
      intraperitoneal co-administration with pristimerin at 4 mg/(kg.d) for 3 d
      dramatically facilitated viral transduction in murine hepatocytes in vivo. The
      transduction efficiency of the tyrosine-mutant rAAV2 vectors as well as that of
      rAAV8 vectors carrying oversized transgene cassette was also augmented
      significantly by pristimerin. The underlying molecular mechanisms by which
      pristimerin mediated the observed increase in the transduction efficiency of rAAV
      vectors include both inhibition of proteasomal degradation of the intracellular
      proteins and enhanced nuclear translocation of the vector genomes. CONCLUSION:
      These studies suggest the potential beneficial use of pristimerin and pristimerin
      containing herb extract in future liver-targeted gene therapy with rAAV vectors.

PMID- 24461593
TI  - Protective effect of diosmin against diabetic neuropathy in experimental rats.
AB  - OBJECTIVE: The present study was undertaken to evaluate the effect of diosmin in
      diabetic neuropathy in type 2 diabetic rats. METHODS: Type 2 diabetes was induced
      in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin
      (35 mg/kg) and high-fat diet. Four weeks after the confirmation of diabetes,
      diabetic rats were treated with diosmin (50 and 100 mg/kg, p.o.) for next 4
      weeks. Rats were evaluated for biochemical, behavioral and oxidative stress
      parameters. Eddy's hot plate and tail immersion test were performed on 6th, 7th,
      8th, 9th and 10th weeks of experiment to assess thermal hyperalgesia and cold
      allodynia respectively. Further, the walking function test was performed for
      assessing the motor responses at the end of the treatment schedule. RESULTS: Rats
      were fed with high-fat diet throughout the experiment schedule and administration
      of low-dose streptozotocin induced significant elevation in blood glucose level
      and insulin resistance which was confirmed by oral glucose tolerance test.
      Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the
      reduced body weight, elevated blood sugar and lipid profiles. Further the dose
      dependent improvement was observed in thermal hyperalgesia, cold allodynia and
      walking function in diabetic rats treated with diosmin. Elevated levels of
      malondialdehyde, and nitric oxide and decreased glutathione levels and superoxide
      dismutase activity in diabetic rats were restored significantly after the 4 weeks
      of diosmin treatment. CONCLUSION: Diosmin has shown beneficial effect in
      preventing the progression of early diabetic neuropathy in rats.

PMID- 24461594
TI  - Gastric antisecretory and cytoprotective effects of hydroalcoholic extracts of
      Plumeria alba Linn. leaves in rats.
AB  - OBJECTIVE: This study was conducted to evaluate the antiulcerogenic property of
      hydroalcoholic extract obtained from the leaves of Plumeria alba Linn. METHODS:
      Antiulcer assays were performed using the protocols of ulcer induced by non
      steroidal anti-inflammatory drugs, ethanol and pylorus ligation. The
      hydroalcoholic extract (HAPA), and various fractions of HAPA like, n-hexane
      extract (HPA), ethyl acetate extract (EAPA) and n-butanol extract (BPA) were
      administered at doses of 200 and 400 mg/kg for HAPA and 100 and 200 mg/kg for
      fractions of extracts. Parameters of gastric secretion (volume, pH, total
      protein, and free and total acidity) were determined by the pylorus ligation
      model. Parameters like aspartate aminotransferase and alanine aminotransferase
      were also determined in ethanol-induced ulcer model. To determine the mechanism
      of action, role of nitric oxide was also evaluated. RESULTS: EAPA and BPA (100
      and 200 mg/kg, p.o.) showed gastric ulcer-healing effect in indomethacin-induced
      ulcer model, while HAPA (200 mg/kg) and HPA showed no significant antiulcer
      effect. Both EAPA and BPA showed gastric cytoprotective effect in ethanol-induced
      gastric ulcer and inhibited gastric secretion in pylorus-ligated rats.
      CONCLUSION: The results of the present study show that some hydroalcoholic
      extract of Plumeria alba L. displays antiulcer activity, as demonstrated by the
      significant inhibition of ulcer formation induced by different models, which is
      consistent with the literature report in folk medicine.

PMID- 24461595
TI  - In-house preparation and characterization of an Ayurvedic bhasma: Praval bhasma.
AB  - OBJECTIVE: To prepare the Praval bhasma (PB) and to perform its characterization.
      METHODS: The preparation was performed strictly as per method prescribed in
      Ayurvedic formulary of India followed by preliminary tests including
      Nischandratva, Rekhapurnatvam, Varitaramtavm, Nisvadutvam and Amla pariksha. The
      physicochemical characterization was done with the use of instrumental techniques
      such as Fourier transform infrared (FTIR) spectroscopy, scanning electron
      microscopy (SEM), X ray diffraction (XRD), and energy dispersive X-ray (EDAX).
      RESULTS: The FTIR bands appearing in final product spectra showed a significant
      shift in infrared vibration frequency as well as intensity when compared with the
      raw material, which was indicative of formulation of bhasma. The XRD analysis
      revealed that raw material contained CaCO3 whereas in case of final product of
      bhasma, CaO was identified. SEM analysis revealed the difference in particles
      size of bhasma (10-15 MUm) and raw material (100-150 MUm). The EDAX analysis
      showed presence of different concentration of carbon in both the samples.
      CONCLUSION: It may be concluded that modern analytical techniques may be involved
      to evaluate the quality aspects of PB. The findings of the present research work
      may be helpful for further formulation and standardization of PB in routine
      analysis.

PMID- 24461596
TI  - Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on
      ethanol-induced fatty liver in rats.
AB  - OBJECTIVE: The present study is aimed at evaluating the protective effects of
      oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute
      ethanol-induced fatty liver in male Wistar rats. METHODS: Ferric reducing
      antioxidant power activity and oxygen radical absorbance capacity of the oils
      were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin
      Forte) and oils from Z. officinale and C. longa before they were exposed to 45%
      ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were
      observed and the degree of protection was measured by using biochemical
      parameters such as alanine aminotransferase, aspartate aminotransferase and
      alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol
      (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione
      S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA)
      levels were estimated. RESULTS: Oils from Z. officinale and C. longa at a dose of
      200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes,
      serum TG, serum TC and hepatic MDA, while they significantly restored the level
      of GSH as well as GST and SOD activities. Histological examination of rats
      tissues was related to the obtained results. CONCLUSION: From the results it may
      be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited
      hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale
      oil was identified to have better effects than C. longa oil.

PMID- 24461597
TI  - Nigella sativa is a safe herbal product.

PMID- 24461598
TI  - Progress meets resistance.

PMID- 24461599
TI  - Can critical-care delirium be treated pharmacologically?

PMID- 24461600
TI  - Long-acting bronchodilators in COPD: an evolving story.

PMID- 24461601
TI  - Tropism of H7N9 influenza viruses in the human respiratory tract.

PMID- 24461602
TI  - COPD in never smokers: prognosis unveiled.

PMID- 24461603
TI  - Better care for patients with COPD and cognitive impairment.

PMID- 24461604
TI  - Innovation in lung health research--a Copernican revolution?

PMID- 24461605
TI  - New insights into pulmonary hypertension.

PMID- 24461606
TI  - Costs of tuberculosis in Europe.

PMID- 24461607
TI  - New guidelines for childhood interstitial lung disease.

PMID- 24461608
TI  - C-reactive protein could predict pneumonia in COPD.

PMID- 24461609
TI  - Financial crisis harms respiratory health in Greece.

PMID- 24461610
TI  - Practising critical care halfway up Everest.

PMID- 24461611
TI  - Daniel De Backer: intensive work for intensive care.

PMID- 24461612
TI  - Effect of intravenous haloperidol on the duration of delirium and coma in
      critically ill patients (Hope-ICU): a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Delirium is frequently diagnosed in critically ill patients and is
      associated with poor clinical outcomes. Haloperidol is the most commonly used
      drug for delirium despite little evidence of its effectiveness. The aim of this
      study was to establish whether early treatment with haloperidol would decrease
      the time that survivors of critical illness spent in delirium or coma. METHODS:
      We did this double-blind, placebo-controlled randomised trial in a general adult
      intensive care unit (ICU). Critically ill patients (>=18 years) needing
      mechanical ventilation within 72 h of admission were enrolled. Patients were
      randomised (by an independent nurse, in 1:1 ratio, with permuted block size of
      four and six, using a centralised, secure web-based randomisation service) to
      receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h,
      irrespective of coma or delirium status. Study drug was discontinued on ICU
      discharge, once delirium-free and coma-free for 2 consecutive days, or after a
      maximum of 14 days of treatment, whichever came first. Delirium was assessed
      using the confusion assessment method for the ICU (CAM-ICU). The primary outcome
      was delirium-free and coma-free days, defined as the number of days in the first
      14 days after randomisation during which the patient was alive without delirium
      and not in coma from any cause. Patients who died within the 14 day study period
      were recorded as having 0 days free of delirium and coma. ICU clinical and
      research staff and patients were masked to treatment throughout the study.
      Analyses were by intention to treat. This trial is registered with the
      International Standard Randomised Controlled Trial Registry, number
      ISRCTN83567338. FINDINGS: 142 patients were randomised, 141 were included in the
      final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group
      spent about the same number of days alive, without delirium, and without coma as
      did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11]
      days; p=0.53). The most common adverse events were oversedation (11 patients in
      the haloperidol group vs six in the placebo group) and QTc prolongation (seven
      patients in the haloperidol group vs six in the placebo group). No patient had a
      serious adverse event related to the study drug. INTERPRETATION: These results do
      not support the hypothesis that haloperidol modifies duration of delirium in
      critically ill patients. Although haloperidol can be used safely in this
      population of patients, pending the results of trials in progress, the use of
      intravenous haloperidol should be reserved for short-term management of acute
      agitation. FUNDING: National Institute for Health Research.

PMID- 24461613
TI  - Once-daily indacaterol versus tiotropium for patients with severe chronic
      obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group
      study.
AB  - BACKGROUND: We compared the efficacy and safety of indacaterol and tiotropium in
      patients with severe chronic obstructive pulmonary disease (COPD) and a history
      of at least one moderate to severe exacerbation in the previous 12 months.
      METHODS: In this multicentre, randomised, blinded, double-dummy, parallel group
      study, we enrolled patients aged 40 years or older with severe COPD and at least
      one exacerbation within the previous year. We used a computer-generated sequence
      to randomly allocate patients (1:1; stratified by baseline inhaled corticosteroid
      use, with the balance of treatments maintained at country level) to receive
      either indacaterol (150 MUg) or tiotropium (18 MUg) once-daily for 52 weeks. Our
      primary and key secondary objectives were to investigate whether indacaterol was
      non-inferior to tiotropium for trough forced expiratory volume in 1 s (FEV1) at
      week 12 (primary endpoint), and for rate of exacerbations at week 52 (secondary
      endpoint). Analysis populations for the primary and key secondary endpoints were
      per-protocol sets. The safety set included all patients who received at least one
      dose of study drug. This study is registered with ClinicalTrials.gov, number
      NCT00845728. FINDINGS: Between March 16, 2009, and July 5, 2012, we enrolled and
      randomly allocated 3444 patients: 1723 to indacaterol and 1721 to tiotropium. At
      week 12, the estimated least squares mean trough FEV1 difference between the
      groups was -0.011 L (least squares mean with indacaterol [n=1450] 1.134 L [SE
      0.008] vs tiotropium [n=1467] 1.145 L [0.008]; one-sided 97.5% CI lower limit 
      0.026 L; p<0.0001). The lower limit of the 97.5% CI was above the prespecified
      non-inferiority margin of -0.055 L, suggesting that indacaterol was non-inferior
      to tiotropium. Indacaterol did not show non-inferiority in terms of annualised
      exacerbation rates: 0.79 (indacaterol, n=1529) versus 0.61 (tiotropium, n=1543);
      ratio 1.29 (one-sided 97.5% CI upper limit 1.44). In the safety set, we recorded
      no between-group difference in the number of patients who had adverse events
      (indacaterol 1119 [65%] of 1721 patients vs tiotropium 1065 [62%] of 1718
      patients) or serious adverse events (indacaterol, 263 [15%] of 1721 patients vs
      tiotropium, 255 [15%] of 1718 patients). Respiratory disorders, particularly
      worsening of COPD, were the most common adverse events (COPD: indacaterol, 747
      [43%] of 1721 patients and tiotropium, 665 [39%] of 1718 patients) and serious
      adverse events (COPD: indacaterol, 147 [9%] of 1721 patients and tiotropium, 121
      [7%] of 1718 patients). INTERPRETATION: Indacaterol and tiotropium provided
      clinically relevant improvements in lung function with comparable safety
      profiles. Tiotropium afforded greater protection from exacerbations, although the
      absolute number of events was small and the difference between treatments is of
      uncertain clinical importance. The present data offer evidence consistent with
      current guidelines. FUNDING: Novartis Pharma AG.

PMID- 24461614
TI  - Tropism and innate host responses of a novel avian influenza A H7N9 virus: an
      analysis of ex-vivo and in-vitro cultures of the human respiratory tract.
AB  - BACKGROUND: Since March, 2013, an avian-origin influenza A H7N9 virus has caused
      severe pneumonia in China. The aim of this study was to investigate the
      pathogenesis of this new virus in human beings. METHODS: We obtained ex-vivo
      cultures of the human bronchus, lung, nasopharynx, and tonsil and in-vitro
      cultures of primary human alveolar epithelial cells and peripheral blood monocyte
      derived macrophages. We compared virus tropism and induction of proinflammatory
      cytokine responses of two human influenza A H7N9 virus isolates,
      A/Shanghai/1/2013 and A/Shanghai/2/2013; a highly pathogenic avian influenza H5N1
      virus; the highly pathogenic avian influenza H7N7 virus that infected human
      beings in the Netherlands in 2003; the 2009 pandemic influenza H1N1 virus, and a
      low pathogenic duck H7N9 virus that was genetically different to the human
      disease causing A H7N9 viruses. FINDINGS: Both human H7N9 viruses replicated
      efficiently in human bronchus and lung ex-vivo cultures, whereas duck/H7N9 virus
      failed to replicate in either. Both human A H7N9 viruses infected both ciliated
      and non-ciliated human bronchial epithelial cells and replicated to higher titres
      than did H5N1 (p<0.0001 to 0.0046) and A/Shanghai/1/2013 replicated to higher
      titres than did H7N7 (p=0.0002-0.01). Both human A H7N9 viruses predominantly
      infected type II alveolar epithelial cells and alveolar macrophages in the human
      lung and replicated to higher titres than did H5N1 (p<0.0001 to 0.0078);
      A/Shanghai/1/2013 replicated to higher titres than did H1N1 (p=0.0052-0.05) and
      H7N7 (p=0.0031-0.0151). Human H7N9 viruses were less potent inducers of
      proinflammatory cytokines compared with H5N1 virus. INTERPRETATION: Collectively,
      the results suggest that the novel H7N9 viruses are better adapted to infect and
      replicate in the human conducting and lower airways than are other avian
      influenza viruses, including H5N1, and pose an important pandemic threat.
      FUNDING: Area of Excellence Scheme of the University Grants Committee (AoE/M
      12/96), Hong Kong Special Administrative Region.

PMID- 24461615
TI  - Characteristics and outcomes of chronic obstructive pulmonary disease in never
      smokers in Denmark: a prospective population study.
AB  - BACKGROUND: A substantial proportion of patients with chronic obstructive
      pulmonary disease (COPD) have never smoked. We tested the hypothesis that, in
      individuals with COPD, never smokers have different characteristics and less
      severe outcomes of the disease than smokers do. METHODS: We included individuals
      from the Copenhagen General Population Study, a prospective population study. We
      identified individuals with COPD spirometrically; that is, as the ratio between
      forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) under the
      lower limit of normal (LLN), excluding individuals with self-reported asthma. We
      examined general characteristics, symptoms, disease severity, and levels of
      inflammatory biomarkers and alpha1-antitrypsin at baseline. We assessed risk of
      lung-related hospital admissions, cardiovascular comorbidities, and all-cause
      mortality during a median follow-up of 4 years (IQR 2.5-5.6). FINDINGS: Between
      Nov 26, 2003, and July 29, 2010, 68,501 participants from the Copenhagen General
      Population Study had lung function measurements and complete information on
      smoking habits available. Of those, we identified 6623 with COPD and no asthma.
      Of these, 1476 (22%) were never smokers, 2696 (41%) former smokers, and 2451
      (37%) current smokers. For comparison we included 24,529 never smokers without
      COPD. Never smokers with COPD had different clinical characteristics, fewer
      symptoms, milder disease, and lower levels of inflammatory biomarkers than did
      current and former smokers with COPD. During follow-up, HRs for hospital
      admission due to COPD were 8.6 (95% CI 5.3-14) in never smokers, 30 (22-41) in
      former smokers, and 43 (32-59) in current smokers compared with never smokers
      without COPD. HRs for hospital admission due to pneumonia were 1.9 (1.4-2.6) in
      never smokers, 2.8 (2.3-3.4) in former smokers, and 3.4 (2.9-4.2) in current
      smokers. For hospital admission due to lung cancer, HRs were 11 (5.7-23) in
      former smokers and 18 (9.2-35) in current smokers, whereas no cases were noted in
      never smokers. Furthermore, risk of cardiovascular comorbidities and all-cause
      mortality was increased in former and current smokers but not in never smokers
      with COPD. INTERPRETATION: Compared with current and former smokers, never
      smokers with COPD had different characteristics and milder disease, limited to
      the lungs. However, morbidity due to lung-related hospital admissions was
      nonetheless substantial in never smokers with COPD. FUNDING: Herlev Hospital,
      Copenhagen University Hospital, Copenhagen County Foundation, and University of
      Copenhagen.

PMID- 24461616
TI  - Lung cancer: potential targets for immunotherapy.
AB  - Lung cancer is the most common cause of cancer-related mortality worldwide and a
      therapeutic challenge. Recent success with antibodies blocking immune checkpoints
      in non-small-cell lung cancers (NSCLC) highlights the potential of immunotherapy
      for lung cancer treatment, and the need for trials of combination regimens of
      immunotherapy plus chemotherapy that lead to immunogenic cell death. Here, we
      review the development of immunogenic cytotoxic compounds, vaccines, and
      antibodies in NSCLC, in view of their integration into personalised oncology. 

PMID- 24461617
TI  - Bronchodilator reversibility in chronic obstructive pulmonary disease: use and
      limitations.
AB  - The change in forced expiratory volume in 1 s (FEV1) after administration of a
      short-acting bronchodilator has been widely used to identify patients with
      chronic obstructive pulmonary disease (COPD) who have a potentially different
      disease course and response to treatment. Despite the apparent simplicity of the
      test, it is difficult to interpret or rely on. Test performance is affected by
      the day of testing, the severity of baseline lung-function impairment, and the
      number of drugs given to test. Recent data suggest that the response to
      bronchodilators is not enhanced in patients with COPD and does not predict
      clinical outcomes. In this Review we will discuss the insight that studies of
      bronchodilator reversibility have provided into the nature of the COPD, and how
      the abnormal physiology seen in patients with this disorder can be interpreted. 

PMID- 24461618
TI  - Childhood pneumonia in developing countries.
AB  - Pneumonia is a widespread and common infectious lung disease that causes
      inflammation, which can lead to reduced oxygenation, shortness of breath, and
      death. An estimated nearly 1.2 million children younger than 5 years died in 2011
      from pneumonia. Most of these deaths occured in developing countries where access
      to care is limited and interventions that have improved care in developed
      countries are scarce. Despite substantial increases in our understanding of the
      clinical syndrome of pneumonia and its aetiologies, its accurate diagnosis is
      challenging when clinical indicators are relied on, and improves only modestly
      with addition of laboratory, microbiological, or radiographical tests. Prevention
      programmes and treatment guidelines have led to impressive reductions in disease,
      but children remain at risk of misdiagnosis and inadequate treatment. Research to
      address challenges in the aetiological diagnosis of pneumonia and widespread
      implementation of treatment interventions beyond vaccines and antibiotics are
      necessary to mitigate the burden of pneumonia and improve child survival.

PMID- 24461619
TI  - Regulation of e-cigarettes: the users' perspective.

PMID- 24461620
TI  - Thirty-day mortality after elective hip and knee arthroplasty.
AB  - BACKGROUND: Hip and knee arthroplasties are very common operations in the UK with
      over 150,000 hip and knee arthroplasties taking place in England and Wales in
      2011. Fortunately mortality following these operations is rare. This study aimed
      to evaluate the incidence and causes of death within 30 days after undergoing hip
      or knee arthroplasty in our unit and to highlight possible risk factors. METHODS:
      We looked at 30-day mortality in all patients undergoing hip or knee arthroplasty
      in our institution between 2005 and 2011. Data on post-operative deaths was
      requested from the Information Services Division (ISD) and correlated with
      procedural and demographic data from our hospital Patient Administration System
      (PAS). The notes of all patients who died within 30 days were reviewed to collect
      data on co-morbid conditions, pre-operative investigations, post-operative
      thromboprophylaxis and cause of death. All primary and revision knee and hip
      arthroplasties including bilateral procedures were included. Arthroplasty for
      trauma was excluded. RESULTS: 12,243 patients underwent hip or knee arthroplasty
      within the study period. The male:female ratio was 2:3. The mean age was 68 with
      a range of 21-91. Ten patients died giving a 30-day mortality rate of 0.08%. The
      most common cause of death was myocardial infarction (7/10 patients).
      CONCLUSIONS: Our finding of a mortality rate of 0.08% is similar or lower to
      those found in previous studies. To our knowledge this is the first series of
      this size looking at mortality from hip and knee arthroplasty within a single
      centre in the UK.

PMID- 24461621
TI  - Performance and awareness in the Iowa Gambling Task.
AB  - Newell & Shanks (N&S) conclude that healthy participants learn to differentiate
      between the good and bad decks of the Iowa Gambling Task, and that healthy
      participants even have conscious knowledge about the task's payoff structure.
      Improved methods of analysis and new behavioral findings suggest that this
      conclusion is premature. 

PMID- 24461622
TI  - Short-term intervention reduces bioelectrical impedance analysis-measured
      visceral fat in type 2 diabetes mellitus.
AB  - In 25 patients with Type 2 diabetes mellitus, the short-term in-hospital calorie
      restriction combined with moderate exercise reduced visceral fat. The reduction
      of visceral fat can improve metabolic cardiovascular risk factors, while the
      reductions in body weight and waist circumference were small and reduction in
      subcutaneous fat was not significant. 

PMID- 24461624
TI  - Initial management of testicular cancer: practice survey among urologists and
      pathologists.
AB  - INTRODUCTION: The objective of this study was to conduct a declarative
      professional practices survey among urologists of the French Association of
      Urology (AFU) and French pathologists concerning their management of testicular
      cancer. MATERIALS AND METHODS: A questionnaire was sent to all urologists,
      members of the AFU, and another questionnaire was sent to French pathologists,
      members of the International Academy of Pathology, French Division, in June 2010.
      A total of 289 urologists (29%) and 84 pathologists (19%) returned the
      questionnaires. RESULTS: Fifty-seven percent of urologists declared that they
      performed fewer than 5 orchidectomies per year. Pathologists declared that they
      examined less than 5 orchidectomy specimens per year in 24% of cases. The
      laboratory work-up (only alpha fetoprotein [AFP], lactate dehydrogenase [LDH],
      and total human chorionic gonadotropin [hCG]) and the radiological work-up (only
      testicular ultrasound and chest, abdomen, and pelvis computed tomography [CT]
      scan) were performed strictly according to guidelines in 15.9% and 65.7% of
      cases, respectively. A total of 31.8% of urologists declared that they performed
      the minimum assessment required by guidelines (AFP, LDH, total hCG, testicular
      ultrasound and chest, abdomen, and pelvis CT scan plus other examinations not
      recommended). Prognostic factors of stage I tumors, to define the indications for
      adjuvant therapy, were correctly declared in 7.3% of nonseminomatous germ cell
      tumors (vascular and/or lymphatic emboli) and in 13.8% of seminomas (tumor size
      >4 cm and rete testis invasion). CONCLUSION: This survey demonstrated that
      clinical practice did not comply with guidelines, which raises the question of
      the measures that can be taken to ensure better application of guidelines or how
      to develop expert centers for the management of these rare tumors.

PMID- 24461623
TI  - Effect of a mixed meal on plasma lipids, insulin resistance and systemic
      inflammation in non-obese Indian adults with normal glucose tolerance and
      treatment naive type-2 diabetes.
AB  - AIM: Asian Indians are believed to have a lower capacity to clear a glucose load
      even during normoglycemia. High post meal glucose levels have been linked to
      postprandial dyslipidemia and generation of proinflammatory cytokines. Since
      humans spend most of their time in the postprandial state, the present study aims
      to evaluate the relationship of insulin resistance (IR) in the basal state with
      dyslipidemia and systemic inflammation (hs-CRP, IL-6 and TNF-a), in the fasting
      state, 2h and 4h after a mixed meal, in Indian adults with normal glucose
      tolerance, and new onset type-2 diabetes. METHODS: Forty-eight people with type 2
      diabetes and 32 individuals with normoglycemia, 30-70 years age, not on
      medications, underwent blood sampling after overnight (12h) fast and 2 and 4h
      after a mixed meal (carbohydrates, proteins and fat content 79.1%, 7.7% and
      13.2%, respectively). RESULTS: Triglyceride (TG), TG/HDL-C (high density
      lipoprotein), HDL-C/LDL-C (low density lipoprotein) ratios, IR parameters, and
      inflammatory markers were significantly higher among patients with diabetes.
      There was a fall in total cholesterol (TC), HDL-C and LDL-C at 2 and 4h after the
      meal in both groups. Compared with fasting, 4-h postprandial TC, TG and HDL-C
      were significantly better positively correlated with IR in normal individuals.
      Postprandial hs-CRP was not significantly different to fasting in both groups.
      Postprandial IL-6 and TNF-alpha were significantly lower in both groups.
      CONCLUSION: Consumption of a carbohydrate rich meal is associated with a rise in
      TG and fall in TC, HDL-C, LDL-C, IL-6 and TNF-alpha among normal individuals and
      people with type 2 diabetes.

PMID- 24461625
TI  - The role of salvage hemiscrotectomy in testicular cancer after scrotal
      contamination: a case report and literature review.

PMID- 24461626
TI  - Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y
      conjugates in treatment of prostate tumors.
AB  - INTRODUCTION: The treatment of prostate cancer using a radiotherapeutic (90)Y
      labeled N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer can be enhanced with
      localized tumor hyperthermia. An (111)In labeled HPMA copolymer system for single
      photon emission computerized tomography (SPECT) was developed to observe the
      biodistribution changes associated with hyperthermia. Efficacy studies were
      conducted in prostate tumor bearing mice using the (90)Y HPMA copolymer with
      hyperthermia. METHODS: HPMA copolymers containing 1, 4, 7, 10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by
      reversible addition-fragmentation transfer (RAFT) copolymerization and
      subsequently labeled with either (111)In for imaging or (90)Y for efficacy
      studies. Radiolabel stability was characterized in vitro with mouse serum.
      Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice.
      Imaging was performed using single photon emission computerized tomography
      (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal
      therapy using gold nanorods. RESULTS: HPMA copolymer-DOTA conjugates demonstrated
      efficient labeling and stability for both radionuclides. Imaging analysis showed
      a marked increase of radiolabeled copolymer within the hyperthermia treated
      prostate tumors, with no significant accumulation in non-targeted tissues. The
      greatest reduction in tumor growth was observed in the hyperthermia treated
      tumors with (90)Y HPMA copolymer conjugates. Histological analysis confirmed
      treatment efficacy and safety. CONCLUSION: HPMA copolymer-DOTA conjugates
      radiolabeled with both the imaging and treatment radioisotopes, when combined
      with hyperthermia can serve as an image guided approach for efficacious treatment
      of prostate tumors.

PMID- 24461627
TI  - Atomic surface diffusion on Pt nanoparticles quantified by high-resolution
      transmission electron microscopy.
AB  - Aberration-corrected high-resolution transmission electron microscopy allows for
      the delocalization-free observation of atomic motions on metallic surfaces and
      thus enables measurements of the diffusion of single atoms on the surfaces of
      nanoscopic objects such as nanoparticles. Using this recently introduced method,
      the diffusion coefficient for surface self-diffusion of Pt nanoparticles is
      determined through the fluctuating occupation of the particle's atomic columns.
      This diffusion coefficient is determined to lie in the range D~(10(-17)...10(
      16)) cm(2)/s.

PMID- 24461628
TI  - Epidemiology of HPV-associated oropharyngeal cancer.
AB  - Squamous cell carcinoma of the oropharynx is increasing in incidence in epidemic
      proportion. This site specific increase in incidence is due to an increase in
      human papillomavirus (HPV)-related squamous cell carcinoma, while the incidence
      of tobacco related squamous cell carcinoma is decreasing. In particular, the
      incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is
      increased among middle aged white men, and sexual behavior is a risk factor. HPV
      related oropharyngeal squamous cell carcinoma represents a growing etiologically
      distinct subset of head and neck cancers with unique epidemiological, clinical,
      and molecular characteristics that differ from those of HPV-unassociated cancers.
      In this review, we discuss the epidemiology of HPV-related OPSCC, the prevalence
      of oral/oropharyngeal HPV infection, and efforts aimed at reducing the incidence
      of HPV-related OPSCC. 

PMID- 24461629
TI  - Prognostic significance of the Wnt pathway in squamous cell laryngeal cancer.
AB  - OBJECTIVES: We sought to determine the prognostic significance of the Wnt
      signaling pathway in operable squamous cell carcinoma of the larynx. MATERIALS
      AND METHODS: In an annotated cohort of 289 operable laryngeal cancers we
      evaluated the prognostic impact of E-cadherin, P-cadherin and beta-catenin
      protein expression with immunohistochemistry, as well as the mRNA expression of 7
      key effectors of the Wnt pathway including secreted frizzled-related protein 4
      (SFRP4), SNAI2 (SLUG) and WNT5A with qPCR (relative quantification [RQ]).
      RESULTS: Using median immunoreactive scores as a pre-defined cut-off, patients
      whose tumors overexpressed both cytoplasmic E-cadherin and beta-catenin
      experienced longer median OS as compared to those whose tumors overexpressed beta
      catenin only (median OS 124 vs. 72 months, p=0.0301) and patients whose tumors
      overexpressed both cytoplasmic and membranous E-cadherin experienced longer DFS
      as compared to those whose tumors overexpressed cytoplasmic E-cadherin only
      (median 118 vs. 91 months, p=0.0106). Upon hierarchical clustering of SFRP4,
      SNAI2 and WNT5A RQ values, profiles including co-expression of all 3 genes but
      also profiles with under-expression of SNAI2 and WNT5A were associated with worse
      outcome as compared to profiles not related to the Wnt pathway. In multivariate
      analysis, clustering was an independent predictor for DFS (p=0.0221) and OS
      (p=0.0077). CONCLUSION: We identified gene expression profiles and IHC patterns
      associated with aberrant Wnt signaling conferring aggressive clinical behavior in
      operable squamous cell carcinoma of the larynx. Prospective validation of these
      results will determine whether targeting the Wnt pathway merits investigation in
      this disease.

PMID- 24461630
TI  - [Basic mechanisms: absorption and excretion of cholesterol and other sterols].
AB  - Cholesterol is of vital importance for vertebrate cell membrane structure and
      function. It is obvious that adequate regulation of cholesterol homeostasis is
      essential. Hypercholesterolemia promotes atherosclerosis and thereby represents a
      major risk factor for cardiovascular disease. The liver has been considered the
      major site of control in maintenance of cholesterol homeostasis. The liver
      facilitates clearance of (very) low density lipoprotein particles and cholesterol
      containing chylomicron remnants, synthesizes cholesterol, synthesizes and
      secretes (nascent) high density lipoprotein particles, secretes cholesterol and
      bile salts to bile, and is involved in reverse cholesterol transport. In recent
      years, however, the importance of the intestine in many aspects of cholesterol
      physiology is increasingly recognized. It has become apparent that direct
      secretion of cholesterol from the blood compartment into the intestine, or
      transintestinal cholesterol excretion, plays a major role in disposal of
      cholesterol via the feces. This review will discuss current knowledge on the
      physiology of cholesterol homeostasis, with emphasis on cholesterol absorption,
      cholesterol synthesis and fecal excretion, and therapeutic options for
      hypercholesterolemia. 

PMID- 24461631
TI  - Continuous home oxygen therapy.
AB  - Oxygen therapy is defined as the therapeutic use of oxygen and consists of
      administering oxygen at higher concentrations than those found in room air, with
      the aim of treating or preventing hypoxia. This therapeutic intervention has been
      shown to increase survival in patients with chronic obstructive pulmonary disease
      (COPD) and respiratory failure. Although this concept has been extended by
      analogy to chronic respiratory failure caused by respiratory and non-respiratory
      diseases, continuous oxygen therapy has not been shown to be effective in other
      disorders. Oxygen therapy has not been shown to improve survival in patients with
      COPD and moderate hypoxaemia, nor is there consensus regarding its use during
      nocturnal desaturations in COPD or desaturations caused by effort. The choice of
      the oxygen source must be made on the basis of criteria such as technical issues,
      patient comfort and adaptability and cost. Flow must be adjusted to achieve
      appropriate transcutaneous oxyhaemoglobin saturation correction. 

PMID- 24461632
TI  - During cooled storage the extender influences processed autophagy marker light
      chain 3 (LC3B) of stallion spermatozoa.
AB  - To investigate the role of the processed autophagy marker light chain 3 (LC3B)
      protein in sperm survival in stallion semen processing during cooled storage,
      split ejaculates were diluted in two different extenders, KMT and INRA 96, and
      LC3B processing and sperm quality evaluated during incubation at 5 degrees C for
      five days. After 3 days of incubation there was a drop in total motility in both
      extenders, although the percentage of progressive motile sperm was greater
      (P<0.05) in samples extended in INRA96. On Day 5 of cooled storage all sperm
      parameters decreased significantly independent of the extender, however, samples
      extended in INRA 96 maintained motility values while those extended in KMT had a
      further decrease in motility compared with data collected on Day 3 of incubation.
      The percentage of live sperm decreased over the time of incubation, but only in
      samples incubated in KMT. The extender had a marked effect in LC3B processing
      during cooled storage. Spermatozoa maintained in KMT extender did not exhibit
      LC3B processing, while in spermatozoa incubated in INRA96 there was an increase
      (P<0.01) in LC3B processing after 5 days of cooled storage. Stallion spermatozoa
      experience LC3B turnover during cooled storage, however, the extent depends on
      the extender used. Apparently LC3B turnover is associated with enhanced survival.

PMID- 24461633
TI  - A review of self-rating instruments to identify young people at risk of bipolar
      spectrum disorders.
AB  - BACKGROUND: Despite 15-25 years being the peak age at onset for bipolar disorder
      (BD), recognition and introduction of appropriate treatment are typically delayed
      by 6 or more years. A major reason for these delays is the failure to identify
      prior mood episodes or risk factors for bipolarity, suggesting that there may be
      a particular benefit in using screening tools in this age group. METHODS: We
      identified papers published between 1980 and 2012 that assessed the validity of
      measures specifically used to screen for BD, risk factors for bipolarity, or a
      prior history of depressive, hypomanic or manic episodes. From these, we
      identified those studies that included sufficient information about participants
      aged 15-25 years. RESULTS: Searches yielded only eleven independent studies with
      available data on the target age group. The studies employed seven separate
      scales that demonstrated quite different screening properties. The cut-off scores
      for optimal sensitivity and specificity often differed from those reported for
      adult samples and varied according to sample characteristics. LIMITATIONS: Our
      findings may be undermined by the small sample sizes and low number of
      individuals in the specified age range included in the studies identified.
      Although we explored all available methods for detecting studies and data sets,
      we cannot exclude the likelihood that other relevant studies on this age range
      exist. CONCLUSIONS: Available screening tools for BD have mainly been validated
      in middle-aged adult samples with established mood disorders, and the instruments
      reviewed show sub-optimal screening properties when applied to adolescents and
      young adults. Overall, those measures that examine personality traits or
      temperament appear to perform better than those assessing discrete symptoms or
      episodes. However, all the measures need further testing and/or modification. In
      the interim, to improve screening for BD in those in the peak age range for onset
      of this disorder, it may be appropriate to combine a measure with high
      sensitivity with one that demonstrates high specificity for a given sampling
      frame.

PMID- 24461634
TI  - Association analysis between suicidal behaviour and candidate genes of bipolar
      disorder and schizophrenia.
AB  - BACKGROUND: The present study investigated associations between the strongest
      joint genetic risk variants for bipolar disorder (BD) and schizophrenia (SCZ) and
      a history of suicide attempt in patients with BD, SCZ and related psychiatric
      disorders. METHODS: A history of suicide attempt was assessed in a sample of 1009
      patients with BD, SCZ and related psychosis spectrum disorders, and associations
      with the joint genetic risk variants for BD and SCZ (rs2239547 (ITIH3/4-region),
      rs10994359 (ANK3) and rs4765905 (CACNA1C)) were investigated. Previously reported
      susceptibility loci for suicide attempt in BD were also investigated.
      Associations were tested by logistic regression with Bonferroni correction for
      multiple testing. RESULTS: The risk allele in rs2239547 (ITIH3/4-region) was
      significantly associated with a history of suicide attempt (p=0.01) after
      multiple testing correction (p threshold<0.017). The previous suicide attempt
      susceptibility loci were only nominally associated, but had the same direction of
      risk in the replication sample (sign test, p=0.02). LIMITATIONS: Relatively small
      sample size and retrospective clinical assessment. CONCLUSIONS: We detected a
      novel association between suicide attempt and the ITIH3/4-region in a combined
      group of patients with BD, SCZ and related psychosis spectrum disorders. This may
      be useful in understanding molecular mechanisms of suicidal behaviour in severe
      mental disorders, although replication is warranted.

PMID- 24461635
TI  - Dismissing subliminal perception because of its famous problems is classic "baby
      with the bathwater".
AB  - Newell & Shanks (N&S) appeal to well-known problems in establishing subliminality
      to argue that there is little convincing evidence that subliminally presented
      stimuli can affect decision making. We discuss how recent studies have
      successfully addressed these well-known problems and, in turn, have revealed
      clear evidence that subliminally presented stimuli can affect decision making. 

PMID- 24461636
TI  - Modeling the partitioning of amino acids in aqueous two phase systems.
AB  - A new model to obtain fast prediction of partition coefficients in
      polymer/polymer aqueous two phase systems (ATPSs) is presented, using amino acids
      as test systems. In particular, the partitioning behavior of eleven amino acids
      (glycine, alanine, leucine, phenylalanine, lysine, arginine, histidine, aspartic
      acid, glutamic acid, glutamine and serine) has been studied in 6 polymer/polymer
      ATPSs, formed by different pairs of nonionic polymers, including polyethylene
      glycol (PEG), Dextran, Ucon and Ficoll at 0.15M NaCl in 0.01M sodium phosphate
      buffer. The partition coefficients of the amino acids in the different ATPSs
      under study showed linear correlations as described by the Collander equation.
      Based on continuum electrostatics (CE), a semi-empirical model was developed to
      study the partitioning behavior in ATPSs. The approach employs a thermodynamic
      cycle where the electrostatic and nonpolar contributions to the free energy of
      partition are assumed to be additive. Three systems were chosen for the modeling
      studies: PEG-Dextran, PEG-Ficoll and Ficoll-Dextran. In general, the model was
      found to correctly predict the preferred phase for the studied amino acids, and,
      except for the charged ones, a good quantitative correlation of the calculated
      and experimental partition free energies was also obtained (e.g., with RMSE
      values of 150Jmol(-1) for PEG-Ficoll). The model performance could be improved by
      grouping amino acids according to their electrostatic properties, resulting in
      very good quantitative partition coefficient predictions (e.g., RMSE values for
      nonpolar amino acids of 29, 16 and 0.4Jmol(-1) for PEG-Dextran, PEG-Ficoll and
      Ficoll-Dextran system, respectively). The good performance of the proposed model
      in predicting partition coefficients of amino acids, the building blocks of
      proteins, offers a good prospect to its application to protein molecules and
      complexes. 

PMID- 24461637
TI  - A study of the methylene/perfluormethylene selectivity of porous polymer
      monolithic stationary phases exhibiting different fluorous/hydrophobic content.
AB  - Porous polymer monolithic columns are prepared from a variety of monomers and
      cross-linkers and can be customized to exhibit different selectivities for
      separate analyte classes. The composition of the monolith can be precisely
      controlled by selecting different monomers and or cross-linker ratios. In this
      work monoliths exhibiting both fluorous and hydrophobic character were prepared
      using butyl methacrylate and its fluorous analogue (monomer) and 1,3-butanediol
      diacrylate and its fluorous analogue (cross-linker) in different ratios. The
      selectivity of the monoliths was probed using capillary electrochromatography
      with several fluorous and alkyl benzene analytes. Hydrophobic stationary phases
      exhibited greater methylene selectivity ( [Formula: see text] ) while those with
      increasing fluorous character show enhanced pefluoromethylene selectivity (
      [Formula: see text] ). The Gibbs free energy change associated with the sorption
      of the analytes on each stationary phase composition can be calculated from
      migration times (i.e. capacity factor) for the addition of an individual -CF2- or
      -CH2- moiety. Furthermore, the Gibbs free energy change associated with a single 
      CF2- or -CH2- moiety (analyte) interacting with an individual -CF2- or -CH2-
      (stationary phase) can also be estimated by plotting fluorous column composition
      against [Formula: see text] . Furthermore [Formula: see text] and [Formula: see
      text] can be plotted versus H2O percentage in mobile phase, and a new concept,
      hypothetical water percentage (HWP) is proposed to evaluate the
      hydrophobicity/fluorophilicity of a stationary phase. 

PMID- 24461638
TI  - Trace determination of primary nerve agent degradation products in aqueous soil
      extracts by on-line solid phase extraction-liquid chromatography-mass
      spectrometry using ZrO2 for enrichment.
AB  - A method for determination of the primary nerve agent degradation products ethyl
      , isopropyl-, isobutyl-, cyclohexyl- and pinacolyl methylphosphonic acid in
      aqueous soil extracts has been developed utilizing on-line solid phase extraction
      liquid chromatography and mass spectrometry (SPE-LC-MS). Four different
      stationary phases (ZrO2, TiO2, polymeric mixed mode anion exchange and porous
      graphitic carbon) were investigated for their suitability as SPE materials in the
      on-line SPE-LC-MS setup. Zirconium dioxide was chosen due to its high affinity
      for the alkyl methylphosphonic acids (AMPAs), and its compatibility with LC-MS.
      Aqueous soil extracts were acidified with 0.1% acetic acid and aliquots of 300MUL
      were injected on a 2mm*10mm ZrO2 column. Separation of the analytes was performed
      on a reversed phase column with acetonitrile/water gradient and 15mM ammonium
      acetate. Method validation was performed with the analytes added to an aqueous
      extract of a loam soil, and the AMPAs could be determined at concentrations as
      low as 0.05-0.5MUgL(-1). The method was linear (R(2)>0.995) from the limit of
      quantification (LOQ) to 100*LOQ, and the within assay repeatability was below 10%
      and 5% relative standard deviation at LOQ and 50*LOQ, respectively. The developed
      method was employed for determination of the AMPAs which had been added to the
      aqueous extracts of five different soil types from cultivated and uncultivated
      areas. The obtained recoveries showed that the analytes could be determined at
      the sensitivities achieved in the method validation in four of the extracts. For
      the first time, we have demonstrated a method capable of detecting primary nerve
      agent degradation products at sub ppb levels in the aqueous extracts of various
      soils. The method requires no sample preparation after soil extraction other than
      pH adjustment of the aqueous extract. 

PMID- 24461639
TI  - Application of liquid-phase microextraction for the determination of sulfur
      compounds in crude oil and diesel.
AB  - A liquid-phase microextraction (LPME) method was for the first time developed for
      the determination of sulfur compounds in Arabian crude oil and diesel. A wide
      range of sulfur compounds, which included benzothiophene, dibenzothiophene and
      their derivatives, was used for model compounds. The analyses were performed by a
      gas chromatography equipped with a sulfur chemiluminescence detector (GC-SCD).
      Under optimum conditions, a linearity was achieved for the extraction sulfur
      compounds between 0.10 and 250MUgmL(-1) with the correlation of determination
      ranging from 0.98 to 0.99. Applying the same optimum conditions, the extraction
      of 77-91% of the sulfur compounds in the Arabian light, Arabian medium and
      Arabian heavy, and diesel was achieved. 

PMID- 24461640
TI  - On-line focusing of 5-hydroxy-tryptamine type 3 receptor antagonists via the
      combination of field-enhanced sample injection and dynamic pH junction in
      capillary electrophoresis with amperometric detection.
AB  - In the present work, an on-line dual focusing technique based on field-enhance
      sample injection (FASI) and dynamic pH junction (DypH) was developed for the
      analysis of two 5-hydroxy-tryptamine type 3 receptor (5-HT3) antagonists
      ondansetron (Ond) and tropisetron (Tro) by capillary electrophoresis with
      amperometric detection (CE-AD) system. By preparing the sample in a lower
      conductivity (FASI condition) and lower pH value (DypH condition) matrix relative
      to the background electrolyte (BGE) solution, a simple and effective dual
      focusing approach, FASI-DypH was achieved. In this stacking mode, a large amount
      of analytes could be electrokinetically injected into the capillary and stacked
      at the boundary of the sample and the BGE zone as a result of deprotonation and
      decrease in the electric field. Effects of separation, detection and FASI-DypH
      focusing conditions were investigated in detail. Under the optimum conditions,
      good separation for Ond and Tro was achieved within 8min. In comparison with the
      conventional CE-AD analysis method, the present dual focusing technique enabled
      the enhancement factors in terms of peak heights to reach 357-fold and 345-fold
      for Ond and Tro, respectively. The limits of detection (LODs) (S/N=3) for Ond and
      Tro were 2nM and 5nM, respectively. The intraday and interday repeatabilities
      (RSDs) were less than 4.5% and 2.9% for peak height and migration time,
      respectively. The proposed method was successfully applied for the analysis of
      Ond and Tro in human urine sample. 

PMID- 24461641
TI  - Surface molecularly imprinted polymers with synthetic dummy template for
      simultaneously selective recognition of nine phthalate esters.
AB  - Dummy template molecularly imprinted polymers (DMIPs) on silica gel particles for
      simultaneously selective recognition of nine phthalate esters have been prepared.
      A novel dummy template molecule with similar structural skeleton to the phthalate
      ester, diethyl N,N'-phthaloyl-bis(11-aminoundecanoate), has been designed and
      synthesized. The DMIP films were grafted on the surface of silica gel particles
      by a sol-gel process with 3-aminopropyltriethoxysilane (APTES) and
      tetramethoxysilane (TEOS) as functional monomer and cross-linker, respectively,
      and the obtained sorbents have been characterized by FTIR with diffuse
      reflectance accessory. The maximum static adsorption capacities of the DMIPs and
      NIP sorbents for the nine phthalate esters were 281 and 132mg/g respectively, and
      the results of dynamic adsorption showed that the adsorption equilibrium could be
      achieved about 5min for the DMIPs sorbents. The imprint factors of the sorbents
      ranged from 1.8 to 3.0 for eight of the phthalate esters except for Diamyl
      phthalate, which indicated that the DMIPs sorbents have high selectivity. The
      competitive experiments of the nine phthalates with some of their analogues on
      the sorbents illustrated that the DMIPs sorbents have high specificity for the
      phthalates. A GC-MS method for determination of the phthalate residues in fruit
      juice have been developed with the DMIPs as sorbents for the solid phase
      extraction (SPE) in the sample pretreatment procedures. The spiking recoveries of
      the phthalates were in the range of 72-100.2% with relative standard deviations
      lower than 10.2%. The results indicated that the obtained sorbents could
      specifically recognize the phthalates from complex matrices, which provide a new
      train of thought for preparing the DMIPs sorbents. 

PMID- 24461642
TI  - Radiofrequency catheter ablation of atypical atrial flutter in dogs.
AB  - Five dogs were presented to our institution for fatigue caused by an incessant
      supraventricular tachycardia. In all dogs, an ECG on admission showed a narrow
      QRS complex tachycardia with a median ventricular cycle length of 220 ms (range
      180-360 ms), and a positive atrial depolarization identifiable in the ST segment
      following the previous QRS complex. There was a 1:1 atrioventricular conduction
      ratio in all but one dog, which presented with 2:1 atrioventricular block.
      Electrophysiologic studies identified the underlying arrhythmogenic mechanism as
      a right atrial macro-reentrant tachycardia with two distinct isthmic areas: right
      septal (RS) in three dogs and right atrial free wall (RAFW) in two dogs. Linear
      radiofrequency catheter ablation was performed during tachycardia in all dogs at
      the identified isthmic area, which acutely blocked the macroreentrant circuit. At
      18-month follow-up, 3 dogs (1 with RAFW isthmus and 2 with RS isthmus) showed no
      recurrence of the arrhythmia on Holter monitoring. One dog with RS isthmus showed
      recurrence of the supraventricular tachycardia 15 days post-ablation, and 1 dog
      with RAFW isthmus presented with persistent atrial fibrillation 2 months post
      ablation.

PMID- 24461643
TI  - Effect of blindfolding on centre of pressure variables in healthy horses during
      quiet standing.
AB  - In a standing horse the centre of pressure (COP), measured as the resultant
      vertical ground reaction force (GRF) of all supporting limbs, is adjusted in
      response to visual, vestibular and proprioceptive information. Stabilographic
      analysis measures balance by tracking COP movements in the horizontal plane. Loss
      of visual input affects stability of balance in people and has clinical
      implications in that instability inherent in some neurological diseases increases
      with the eyes closed. The objectives of this study were to evaluate the visual
      contribution to postural stability in horses. The hypothesis was that the
      magnitude and variability of postural sway variables increases when visual input
      is removed. Vertical GRFs were measured using two synchronized force plates and
      COP movements were tracked in 20 horses as they stood without visible movements
      of the hooves, head or neck. Three trials of 60 s duration were recorded under
      sighted and blindfolded conditions. Stabilographic variables (craniocaudal and
      mediolateral COP amplitudes, velocities and mean power frequencies and their
      within-trial variabilities) were calculated and compared using univariate
      analysis of variance. Compared with the sighted condition, blindfolding increased
      the magnitude and the within-trial variability of craniocaudal and mediolateral
      COP amplitudes and mediolateral COP velocity. The findings indicated that loss of
      visual input had more effect on the measured COP variables in the time domain
      (amplitudes, velocities) than in the frequency domain (mean power frequency). The
      effects of blindfolding on postural stability should be further investigated as
      part of a diagnostic approach to the evaluation of balance in horses with
      neurological impairment.

PMID- 24461644
TI  - Pharmacokinetic profiles of the novel COX-2 selective inhibitor cimicoxib in
      dogs.
AB  - Cimicoxib (CX) is a novel imidazole derivative that is a cyclo-oxygenase (COX)-2
      selective non-steroidal anti-inflammatory drug and the latest COX-2 selective
      inhibitor to be released for veterinary use. Currently there is limited
      information available on the pharmacokinetic (PK) properties of CX. The aim of
      the current study was to evaluate the PK features of CX after administration of
      the recommended dose and after administration of a more variable dose rate in the
      form of the commercially available tablet. In addition, the effects of food
      intake on the PK properties were also evaluated. In the first study, five healthy
      Beagle dogs received 2mg/kg CX via the oral route following a period of fasting.
      The second study was conducted using six healthy Labrador retriever dogs which
      each received an 80 mg tablet (approximate dose 1.95-2.5mg/kg) using a crossover
      design, both in the fasted and fed condition. The plasma concentrations of CX
      were detected by a validated HPLC method. No adverse effects were observed in any
      dogs during the experiment. The results from the PK analysis were similar between
      the studies, regardless of precision of dose and fasted and fed conditions. The
      mean peak concentration of CX was 0.49 and 0.43 MUg/mL under fasted and fed
      conditions, respectively. The mean half-life was about 3h after all treatments.
      In addition, simulated multiple dosing data revealed that time over minimal
      effective concentration was similar after 1.95, 2.0 and 2.5mg/kg dose
      administrations. These findings suggest that slight variation from the
      recommended dose should not alter the therapeutic outcome. In addition, CX can be
      administered to fed dogs without significantly affecting blood levels.

PMID- 24461645
TI  - Ocular manifestations of feline viral diseases.
AB  - Feline viral diseases are common and cats can be presented with a variety of
      clinical manifestations. Ocular disease associated with viral pathogens is not
      unusual, particularly with viruses causing upper respiratory tract disease in
      cats, such as feline herpesvirus type 1 and feline calicivirus. These agents
      mainly cause ocular surface disease. Other viruses, such as feline
      immunodeficiency virus and feline coronavirus, can cause uveitis, while feline
      leukemia virus can induce ocular lymphosarcoma. This review covers the most
      common viral pathogens of cats that cause ocular manifestations, the specific
      features of the ocular diseases caused by these viruses and therapeutic
      recommendations.

PMID- 24461646
TI  - Prevalence of antibodies against feline panleukopenia virus in client-owned cats
      in Southern Germany.
AB  - Feline panleukopenia is a frequent and commonly fatal disease of cats. Recent
      published studies have raised suspicions that some cats fail to develop
      antibodies after vaccination. The purpose of this study was to assess the
      prevalence of antibodies against feline panleukopenia virus (FPV) in cats in
      Southern Germany, and to identify factors that are associated with a lack of
      antibodies. In total, 350 cats presented to the Clinic of Small Animal Medicine,
      Ludwig-Maximilians-Universitaet were randomly included in the study. Information
      regarding signalment, origin, environment, lifestyle, housing conditions, health
      status, chronic diseases, glucocorticoid therapy, and vaccination status were
      collected. Antibodies were detected by haemagglutination inhibition test.
      Asymptomatic chi-squared tests and univariable logistic regression were used to
      investigate associations between a lack of antibodies and the different
      variables. Associations determined to be statistically significant at P<0.1 were
      verified by a multivariable logistic regression analysis. Of the 350 cats, 103
      (29.4%) had no antibodies against FPV. Chronic kidney disease, neoplasia,
      glucocorticoid therapy, and vaccination status were significantly associated with
      a lack of antibodies. The cats with no antibodies were likely to have inadequate
      immunity against panleukopenia and those with chronic diseases or receiving
      glucocorticoids were less likely to be protected. 

PMID- 24461647
TI  - [Low level laser therapy in inflammatory and infectious oral diseases].
AB  - PURPOSE: Low Level Laser Therapy (LLLT) is an increasingly studied technique. The
      authors of a meta-analysis published in 2012 had already confirmed the
      effectiveness of LLLT for radio-induced mucitis. Our purpose was to check its
      indication for similar pathologies. MATERIAL AND METHODS: The articles were
      selected with the PubMed engine. The selected terms were "Low Level Laser
      Therapy", "oral surgery", "oral infection", "oral inflammation", "oral mucosal
      lesions", "oral mucosal disease", "stomatitis", "aphtous", "Herpes", "oral lichen
      planus", and "oral ulceration". The analysis was made on the following criteria:
      assessment criteria, methodological quality, and bias. We estimated the level of
      proof according to Sackett's modified score. RESULTS: Six articles were selected.
      Two focused on the effectiveness of LLLT for Herpes simplex virus 1 oral
      symptoms. Two focused on the effectiveness of LLLT for oral lichen planus. One
      focused on the effectiveness of LLLT for recurrent aphthous stomatitis. The last
      one focused on the usefulness of LLLT to control stomatitis pain in the hand-foot
      and-mouth disease. CONCLUSION: All the selected studies were assessed with a
      Sackett's score of IV. No study presented the required quality standards to
      recommend the treatment of LLLT for the selected indications.

PMID- 24461648
TI  - Association between genetic polymorphisms in apoptosis-related genes and risk of
      cutaneous melanoma in women and men.
AB  - BACKGROUND: The P53 Arg72Pro, MDM2 c.+309T>G, BAX c.-248G>A, and BCL2 c.-717C>A
      polymorphisms have variable roles in the apoptosis pathways. OBJECTIVE: To
      clarify the roles of these polymorphisms in the risk for cutaneous melanoma (CM).
      METHODS: Genomic DNA of 200 CM patients and 215 controls was analyzed by PCR
      RFLP. RESULTS: In women, the frequencies of BAX GG (83.0% vs. 71.0%, P=0.04),
      BCL2 AA (32.0% vs. 15.0%, P=0.003), P53 ArgArg plus BAX GG (84.9% vs. 63.2%,
      P=0.01), P53 ArgArg plus BCL2 AA (37.0% vs. 13.1%, P=0.003), BAX GG plus BCL2 AA
      (70.3% vs. 33.3%, P=0.001), MDM2 GG plus BAX GG plus BCL2 AA (27.3% vs. 3.7%,
      P=0.03), and P53 ArgArg plus MDM2 GG plus BAX GG plus BCL2 AA (33.3% vs. 5.6%,
      P=0.04) genotypes were higher in patients than in controls. Female carriers of
      the respective genotypes were under 1.98 (95% CI: 1.01-3.91), 2.87 (95% CI: 1.43
      5.77), 3.48 (95% CI: 1.34-9.04), 4.23 (95% CI: 1.63-10.96), 6.04 (95% CI: 2.10
      17.37), 25.61 (95% CI: 1.29-507.24), and 25.69 (95% CI: 1.11-593.59)-fold
      increased risks for CM than others, respectively. In men, the frequencies of BCL2
      CA+AA (83.0% vs. 67.6%, P=0.01) and MDM2 TG+GG plus BCL2 CA+AA (94.2% vs. 68.3%,
      P=0.003) genotypes were higher in patients than in controls. Male carriers of the
      respective genotypes were under 2.43 (95% CI: 1.23-4.82) and 9.22 (95% CI: 2.16
      39.31)-fold increased CM risks than others, respectively. CONCLUSION: The data
      suggest for the first time that P53 Arg72Pro, MDM2 c.+309T>G, BAX c.-248G>A, and
      BCL2 c.-717C>A polymorphisms, enrolled in apoptosis pathways, constitute distinct
      determinants of CM in women and men.

PMID- 24461649
TI  - The TASERs are coming, the TASERs are coming-conducted electrical weapons: tools
      to manage and prevent ED violence?

PMID- 24461650
TI  - Rates of lung disease in Europe: an uncomfortable equilibrium.

PMID- 24461651
TI  - What are the causes of global differences in lung function?

PMID- 24461652
TI  - Azithromycin in bronchiectasis: evidence in children?

PMID- 24461653
TI  - Muscle weakness and nutrition in critical illness: matching nutrient supply and
      use.

PMID- 24461654
TI  - Mutation-specific therapy in cystic fibrosis: the earlier, the better.

PMID- 24461658
TI  - KBR appeals $85 million sodium dichromate verdict.

PMID- 24461659
TI  - 2013 annual congress of the European Respiratory Society.

PMID- 24461660
TI  - New statistical model raises hope of better lung nodule management.

PMID- 24461661
TI  - Jane Carter: at the frontline of tuberculosis care.

PMID- 24461662
TI  - Mass gatherings and respiratory disease.

PMID- 24461663
TI  - Global differences in lung function by region (PURE): an international, community
      based prospective study.
AB  - BACKGROUND: Despite the rising burden of chronic respiratory diseases, global
      data for lung function are not available. We investigated global variation in
      lung function in healthy populations by region to establish whether regional
      factors contribute to lung function. METHODS: In an international, community
      based prospective study, we enrolled individuals from communities in 17 countries
      between Jan 1, 2005, and Dec 31, 2009 (except for in Karnataka, India, where
      enrolment began on Jan 1, 2003). Trained local staff obtained data from
      participants with interview-based questionnaires, measured weight and height, and
      recorded forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC).
      We analysed data from participants 130-190 cm tall and aged 34-80 years who had a
      5 pack-year smoking history or less, who were not affected by specified disorders
      and were not pregnant, and for whom we had at least two FEV1 and FVC measurements
      that did not vary by more than 200 mL. We divided the countries into seven
      socioeconomic and geographical regions: south Asia (India, Bangladesh, and
      Pakistan), east Asia (China), southeast Asia (Malaysia), sub-Saharan Africa
      (South Africa and Zimbabwe), South America (Argentina, Brazil, Colombia, and
      Chile), the Middle East (Iran, United Arab Emirates, and Turkey), and North
      America or Europe (Canada, Sweden, and Poland). Data were analysed with non
      linear regression to model height, age, sex, and region. FINDINGS: 153,996
      individuals were enrolled from 628 communities. Data from 38,517 asymptomatic,
      healthy non-smokers (25,614 women; 12,903 men) were analysed. For all regions,
      lung function increased with height non-linearly, decreased with age, and was
      proportionately higher in men than women. The quantitative effect of height, age,
      and sex on lung function differed by region. Compared with North America or
      Europe, FEV1 adjusted for height, age, and sex was 31.3% (95% CI 30.8-31.8%)
      lower in south Asia, 24.2% (23.5-24.9%) lower in southeast Asia, 12.8% (12.4
      13.4%) lower in east Asia, 20.9% (19.9-22.0%) lower in sub-Saharan Africa, 5.7%
      (5.1-6.4%) lower in South America, and 11.2% (10.6-11.8%) lower in the Middle
      East. We recorded similar but larger differences in FVC. The differences were not
      accounted for by variation in weight, urban versus rural location, and education
      level between regions. INTERPRETATION: Lung function differs substantially
      between regions of the world. These large differences are not explained by
      factors investigated in this study; the contribution of socioeconomic, genetic,
      and environmental factors and their interactions with lung function and lung
      health need further clarification. FUNDING: Full funding sources listed at end of
      the paper (see Acknowledgments).

PMID- 24461664
TI  - Long-term azithromycin for Indigenous children with non-cystic-fibrosis
      bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention
      Study): a multicentre, double-blind, randomised controlled trial.
AB  - BACKGROUND: Indigenous children in high-income countries have a heavy burden of
      bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long
      term azithromycin reduced pulmonary exacerbations in Indigenous children with non
      cystic-fibrosis bronchiectasis or chronic suppurative lung disease. METHODS:
      Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori,
      and Pacific Island children aged 1-8 years with either bronchiectasis or chronic
      suppurative lung disease into a multicentre, double-blind, randomised, parallel
      group, placebo-controlled trial. Eligible children had had at least one pulmonary
      exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by
      computer-generated sequence with permuted block design, stratified by study site
      and exacerbation frequency [1-2 vs >=3 episodes in the preceding 12 months]) to
      receive either azithromycin (30 mg/kg) or placebo once a week for up to 24
      months. Allocation concealment was achieved by double-sealed, opaque envelopes;
      participants, caregivers, and study personnel were masked to assignment until
      after data analysis. The primary outcome was exacerbation (respiratory episodes
      treated with antibiotics) rate. Analysis of the primary endpoint was by intention
      to treat. At enrolment and at their final clinic visits, children had deep nasal
      swabs collected, which we analysed for antibiotic-resistant bacteria. This study
      is registered with the Australian New Zealand Clinical Trials Registry;
      ACTRN12610000383066. FINDINGS: 45 children were assigned to azithromycin and 44
      to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011,
      thus children received the intervention for 12-24 months. The mean treatment
      duration was 20.7 months (SD 5.7), with a total of 902 child-months in the
      azithromycin group and 875 child-months in the placebo group. Compared with the
      placebo group, children receiving azithromycin had significantly lower
      exacerbation rates (incidence rate ratio 0.50; 95% CI 0.35-0.71; p<0.0001).
      However, children in the azithromycin group developed significantly higher
      carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving
      placebo (four of 37, 11%; p=0.002). The most common adverse events were non
      pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209
      events in the placebo group) and bronchiectasis-related events (episodes or
      investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in
      the placebo group); however, study drugs were well tolerated with no serious
      adverse events being attributed to the intervention. INTERPRETATION: Once-weekly
      azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous
      children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung
      disease. However, this strategy was also accompanied by increased carriage of
      azithromycin-resistant bacteria, the clinical consequences of which are
      uncertain, and will need careful monitoring and further study. FUNDING: National
      Health and Medical Research Council (Australia) and Health Research Council (New
      Zealand).

PMID- 24461665
TI  - Effect of tolerating macronutrient deficit on the development of intensive-care
      unit acquired weakness: a subanalysis of the EPaNIC trial.
AB  - BACKGROUND: Patients who are critically ill can develop so-called intensive-care
      unit acquired weakness, which delays rehabilitation. Reduced muscle mass,
      quality, or both might have a role. The Early Parenteral Nutrition Completing
      Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered
      with ClinicalTrials.gov, number NCT00512122) showed that tolerating macronutrient
      deficit for 1 week in intensive-care units (late parenteral nutrition [PN])
      accelerated recovery compared with early PN. The role of weakness was unclear.
      Our aim was to assess whether late PN and early PN differentially affect muscle
      weakness and autophagic quality control of myofibres. METHODS: In this
      prospectively planned subanalysis of the EPaNIC trial, weakness (MRC sum score)
      was assessed in 600 awake, cooperative patients. Skeletal muscle biopsies,
      harvested from 122 patients 8 days after randomisation and from 20 matched
      healthy controls, were studied for autophagy and atrophy. We determined the
      significance of differences with Mann-Whitney U, Median, Kruskal-Wallis, or
      chi(2) (exact) tests, as appropriate. FINDINGS: With late PN, 105 (34%) of 305
      patients had weakness on first assessment (median day 9 post-randomisation)
      compared with 127 (43%) of 295 patients given early PN (absolute difference -9%,
      95% CI -16 to -1; p=0.030). Weakness recovered faster with late PN than with
      early PN (p=0.021). Myofibre cross-sectional area was less and density was lower
      in critically ill patients than in healthy controls, similarly with early PN and
      late PN. The LC3 (microtubule-associated protein light chain 3) II to LC3I ratio,
      related to autophagosome formation, was higher in patients given late PN than
      early PN (p=0.026), reaching values almost double those in the healthy control
      group (p=0.0016), and coinciding with less ubiquitin staining (p=0.019). A higher
      LC3II to LC3I ratio was independently associated with less weakness (p=0.047).
      Expression of mRNA encoding contractile myofibrillary proteins was lower and E3
      ligase expression higher in muscle biopsies from patients than in control
      participants (p<=0.0006), but was unaffected by nutrition. INTERPRETATION:
      Tolerating a substantial macronutrient deficit early during critical illness did
      not affect muscle wasting, but allowed more efficient activation of autophagic
      quality control of myofibres and reduced weakness. FUNDING: UZ Leuven, Research
      Foundation-Flanders, the Flemish Government, and the European Research Council.

PMID- 24461666
TI  - Assessment of clinical response to ivacaftor with lung clearance index in cystic
      fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a
      randomised controlled trial.
AB  - BACKGROUND: Ivacaftor has shown a clinical benefit in patients with cystic
      fibrosis who have the G551D-CFTR mutation and reduced lung function. Lung
      clearance index (LCI) using multiple-breath washout might be an alternative to
      and more sensitive method than forced expiratory volume in 1 s (FEV1) to assess
      treatment response in the growing number of children and young adults with cystic
      fibrosis who have normal spirometry. The aim of the study was to assess the
      treatment effects of ivacaftor on LCI in patients with cystic fibrosis, a G551D
      CFTR mutation, and an FEV1 >90% predicted. METHODS: This phase 2, multicentre,
      placebo-controlled, double-blind 2*2 crossover study of ivacaftor treatment was
      conducted in patients with cystic fibrosis, at least one G551D-CFTR allele, and
      an FEV1 >90% predicted. Patients also had to have an LCI higher than 7.4 at
      screening, age of 6 years or older, and a weight higher than or equal to 15 kg.
      Eligible patients were randomly allocated to receive one of two treatment
      sequences (placebo first followed by ivacaftor 150 mg twice daily [sequence 1] or
      ivacaftor 150 mg twice daily first followed by placebo [sequence 2]) of 28 days'
      treatment in each period, with a 28-day washout between the two treatment
      periods. Randomisation (ratio 1:1) was done with block sizes of 4, and all site
      personnel including the investigator, the study monitor, and the Vertex study
      team were masked to treatment assignment. The primary outcome measure was change
      from baseline in LCI. The study is registered at ClinicalTrials.gov, NCT01262352.
      FINDINGS: Between February and November, 2011, 21 patients were enrolled, of
      which 11 were assigned to the sequence 1 group, and 10 to the sequence 2 group.
      20 of these patients received treatment and 17 completed the trial (eight in
      sequence 1 group and 9 in sequence 2 group). Treatment with ivacaftor led to
      significant improvements compared with placebo in LCI (difference between groups
      in the average of mean changes from baseline at days 15 and 29 was -2.16 [95% CI 
      2.88 to -1.44]; p<0.0001). Adverse events experienced by study participants were
      similar between treatment groups; at least one adverse event was reported by 15
      (79%) of 19 patients who received placebo and 13 (72%) of 18 patients who
      received ivacaftor. No deaths occurred during study period. INTERPRETATION: In
      patients with cystic fibrosis aged 6 years or older who have at least one G551D
      CFTR allele, ivacaftor led to improvements in LCI. LCI might be a more sensitive
      alternative to FEV1 in detecting response to intervention in these patients with
      mild lung disease. FUNDING: Vertex Pharmaceuticals Incorporated.

PMID- 24461667
TI  - New treatments for severe treatment-resistant asthma: targeting the right
      patient.
AB  - Guidelines for asthma management focus on the use of combination inhaled
      treatment with corticosteroids and longacting beta-agonists for symptomatic
      asthma. In more severe disease, other drugs such as leukotriene blockers and slow
      release oral theophylline are added, with oral corticosteroids and anti
      immunoglobulin E treatment with omalizumab for the most severe cases of asthma.
      Once-daily longacting beta-agonists and inhaled corticosteroids are being
      developed. Longacting muscarinic antagonists might also provide additive benefit.
      New approaches are needed for the treatment of severe asthma, but patients need
      to be endotyped so that they can be directed for specific treatments. This Review
      focuses on the role of eosinophilic and neutrophilic inflammation, the attributes
      of chronic airflow obstruction, and the notion of corticosteroid insensitivity
      because potential targets for treatment have started to emerge from such
      analyses. How the best phenotypic or even better, the best endotypic responder
      with each new treatment, can be established will also be discussed. Newer
      treatments for asthma will emerge from better endotyping, leading to personalised
      medicine in asthma. 

PMID- 24461668
TI  - Severity assessment scores to guide empirical use of antibiotics in community
      acquired pneumonia.
AB  - Severity assessment scores were first developed to predict the 30 day mortality
      in community acquired pneumonia; however, several guidelines have extended their
      use to guide empirical antibiotic prescription decisions. This approach has
      theoretical advantages because a decrease in broad-spectrum antibiotic treatment
      in low-risk patients might reduce antibiotic-related side-effects, and to give
      broad-spectrum therapy to patients at higher risk of death is intuitive. However,
      evidence in support of this approach is not clear. In particular, the British
      Thoracic Society guidelines suggest withholding a macrolide from patients with
      low CURB 65 scores, despite evidence that these patients have a higher frequency
      of atypical pathogens than do those with a higher severity of pneumonia. Severity
      scores do not perform well in some groups and might overestimate disease severity
      in elderly people, leading to inappropriate broad-spectrum treatment to those at
      high risk of complications such as Clostridium difficile infection. In this
      Review, we discuss the evidence for antibiotic prescribing guided by severity
      score and suggest that more evidence of effect and implementation is needed
      before this approach can be universally adopted. 

PMID- 24461669
TI  - Hope for haloperidol in delirium.

PMID- 24461670
TI  - Prophylactic haloperidol: too early to lose hope.

PMID- 24461671
TI  - Prophylactic haloperidol: too early to lose hope - author's reply.

PMID- 24461672
TI  - The problem of the null in the verification of unconscious cognition.
AB  - Newell & Shanks (N&S) argue that when awareness measures are more reliable and
      valid, greater evidence of awareness of supposedly unconscious influences is
      revealed. A related issue is that unconsciousness is typically the null
      hypothesis that evidence of awareness will not emerge. As it is difficult to
      conclude the null, it is also difficult to conclude a lack of conscious
      awareness. 

PMID- 24461673
TI  - Rituximab decreases without preference all subclasses of IgG anti-BP180
      autoantibodies in refractory bullous pemphigoid (BP).

PMID- 24461676
TI  - Ultrasound in placental disorders.
AB  - The definition of placenta previa based on ultrasound findings is more practical,
      and the traditional definition (implantation of the placenta in the lower uterine
      segment) needs to be revised. The term 'placenta previa' should only be used when
      the placental edge overlaps or is within 2 cm of the internal cervical orifice in
      late pregnancy. If the placental edge is located further than 2 cm but within 3.5
      cm from the internal cervical orifice, the placenta should be termed 'low-lying'.
      Unless the placental edge at least reaches the internal orifice at mid-trimester,
      symptomatic placenta previa in the third trimester will not be encountered.
      Caesarean section is the recommended mode of delivery for placenta previa at
      term. Attempt at vaginal delivery is appropriate for low-lying placenta, but the
      possibility of post-partum haemorrhage should be kept in mind. The incidence of
      invasive placentation, such as placenta accrete, has progressively risen in the
      past 3 decades, possibly as a consequence of increasing caesarean section rates.
      Ultrasound has a sensitivity of 91% and a specificity of 97% for the
      identification of all forms of invasive placentation. Chorioangiomas are benign
      non-trophoblastic placental tumours with excessive vascular proliferation within
      the stroma of chronic villi. They are usually asymptomatic, although occasionally
      can be associated with adverse fetal outcomes. Chorioangiomas usually appear as
      well-circumscribed, rounded, hypo-echoic lesions next to the chorionic surface.
      Iatrogenic delivery or prenatal intervention are two options, if fetal compromise
      is present. Prenatal detection leads to a dramatic increase in survival compared
      with those cases unsuspected antenatally.

PMID- 24461674
TI  - Oculocutaneous albinism (OCA) in Japanese patients: five novel mutations.

PMID- 24461675
TI  - Fibroblasts from patients affected by Pseudoxanthoma elasticum exhibit an altered
      PPi metabolism and are more responsive to pro-calcifying stimuli.
AB  - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by
      progressive calcification of soft connective tissues. The pathogenesis is still
      hard to pin down. In PXE dermal fibroblasts, in addition to impaired
      carboxylation of the vitamin K-dependent inhibitor matrix Gla protein (MGP), we
      have also demonstrated an up-regulation of alkaline phosphatase activity. In the
      light of these data we have suggested that both calcium and phosphate metabolism
      might be locally altered, both pathways acting in synergy on the occurrence of
      matrix calcification. OBJECTIVE: This study aims to better explore if cultured
      PXE fibroblasts, compared to control cells, exhibit a modified inorganic
      pyrophosphate (PPi) metabolism and are more responsive to pro-calcifying stimuli.
      METHODS: Primary human dermal fibroblasts isolated from healthy individuals and
      from PXE patients were cultured for different time points in standard and in pro
      calcifying media. The expression of ANKH/ANKH, ENPP1/PC1, ALPL/TNAP, SPP1/OPN was
      evaluated by qRT-PCR and Western blot, respectively. TNAP activity was measured
      by spectrophotometric analyses, whereas calcification was investigated by light
      and electron microscopy as well as by micro-analytical techniques. RESULTS: In
      the presence of pro-calcifying stimuli, dermal fibroblasts alter their phenotype
      favouring matrix mineralization. In particular, ENPP1/PC1 and SPP1/OPN
      expression, as well as TNAP activity, was differently expressed in control and in
      PXE fibroblasts. Moreover, in pathologic cells the ratio between factors
      favouring and reducing PPi availability exhibits a more pronounced shift towards
      a pro-calcifying balance. CONCLUSION: PXE fibroblasts are more susceptible to pro
      calcifying stimuli and in these cells an altered PPi metabolism contributes to
      matrix calcification.

PMID- 24461677
TI  - Reality and renovascular disease: when does renal artery stenosis warrant
      revascularization?

PMID- 24461678
TI  - The umpire's call: safe at home, but the game is not over.

PMID- 24461679
TI  - Bloodstream infection prevention in ESRD: forging a pathway for success.

PMID- 24461680
TI  - In reply to 'training can be cost-effective in reducing morbidity associated with
      temporary hemodialysis catheter insertion'.

PMID- 24461681
TI  - Training can be cost-effective in reducing morbidity associated with temporary
      hemodialysis catheter insertion.

PMID- 24461682
TI  - Quiz page February 2014: swollen kidneys and a pancreatic mass.

PMID- 24461684
TI  - Cannabis use, gender and age of onset of schizophrenia: data from the AESOP
      study.
AB  - An earlier age of onset of schizophrenia has been identified as a poor prognostic
      indicator. The current study examines the interaction effect of gender and
      cannabis use on age of onset of schizophrenia and schizoaffective disorder. This
      research forms part of a two-centre epidemiological study of first-episode
      psychosis and included individuals with a diagnosis of schizophrenia or
      schizoaffective disorder and an age of onset between age 16 and 45. Kaplan-Meier
      curves and Cox proportional hazards regression were used to compare the effects
      of cannabis use and gender on age of first symptom of schizophrenia. Akaike's
      information criteria were used to find the model with the best fit to the data.
      Cannabis users had an earlier age of first symptom than non-users. There was an
      interaction with gender; the gender difference in age of onset was diminished in
      cannabis smokers compared with non-cannabis smokers. The model including cannabis
      use interacting with gender was the most parsimonious model, followed by cannabis
      use alone. The addition of other illegal drug use did not improve the model.
      Cannabis use is associated with an earlier age of onset of schizophrenia, and the
      gender difference in age of onset is reduced among cannabis smokers. 

PMID- 24461685
TI  - Knowledge corruption for visual perception in individuals high on paranoia.
AB  - Studies revealed that patients with paranoid schizophrenia display overconfidence
      in errors for memory and social cognition tasks. The present investigation
      examined whether this pattern holds true for visual perception tasks. Nonclinical
      participants were recruited via an online panel. Individuals were asked to
      complete a questionnaire that included the Paranoia Checklist and were then
      presented with 24 blurry pictures; half contained a hidden object while the other
      half showed snowy (visual) noise. Participants were asked to state whether the
      visual items contained an object and how confident they were in their judgment.
      Data from 1966 individuals were included following a conservative selection
      process. Participants high on core paranoid symptoms showed a poor calibration of
      confidence for correct versus incorrect responses. In particular, participants
      high on paranoia displayed overconfidence in incorrect responses and demonstrated
      a 20% error rate for responses made with high confidence compared to a 12% error
      rate in participants with low paranoia scores. Interestingly, paranoia scores
      declined after performance of the task. For the first time, overconfidence in
      errors was demonstrated among individuals with high levels of paranoia using a
      visual perception task, tentatively suggesting it is a ubiquitous phenomenon. In
      view of the significant decline in paranoia across time, bias modification
      programs may incorporate items such as the one employed here to teach patients
      with clinical paranoia the fallibility of human cognition, which may foster
      subsequent symptom improvement. 

PMID- 24461686
TI  - [Abdominal pain in progressive encephalomyelitis with rigidity].
AB  - INTRODUCTION: Stiff-person syndrome is rare neurological disease, associating
      trunk rigidity and painful muscular spasms. A clinical variant of stiff person
      syndrome is the progressive encephalomyelitis with rigidity and myoclonus (PERM),
      which includes neurological cognitive disturbances. CASE REPORT: We report a 73
      year-old woman initially addressed for abdominal pain, anorexia and severe weight
      loss, for whom diagnosis of PERM was made. CONCLUSION: Because of its various
      clinical presentations, sometimes without evidence for neurological disease, the
      diagnosis of PERM is delayed. The presence of antineuropile antibodies associated
      with muscular spasms at electromyogram are strong evidence for this diagnosis.

PMID- 24461687
TI  - Bilateral hippocampal malformation and concurrent granulomatous
      meningoencephalitis in a dog with refractory epilepsy.
AB  - A 5-year-old dog was referred with a history of anorexia and apathy for 3 weeks
      and acute status epilepticus. Ten weeks later the animal was humanely destroyed
      due to refractory epilepsy despite anti-epileptic medical treatment.
      Microscopical examination of the brain revealed bilateral malformation of the
      dentate gyrus with abnormal gyration. Cornu ammonis segments comprised of sparse
      pyramidal cells accompanied by marked gliosis. Additionally, there was severe
      generalized disseminated granulomatous meningoencephalitis, mainly localized to
      the white matter of the cerebral hemispheres. This is the first description of
      bilateral hippocampal malformation in a dog. 

PMID- 24461688
TI  - The transition to motherhood: towards a broader understanding of perinatal
      distress.
AB  - BACKGROUND: A substantial body of research has focused on maternal perinatal mood
      and wellbeing, with the focus predominantly being on depression, and to a lesser
      extent, anxiety. Perinatal maternal stress has also been investigated recently,
      but to a far lesser extent. The present paper questions whether the term
      'perinatal distress' accurately captures the range of challenges experienced by
      women during the perinatal period, when the scope of 'distress' is limited to the
      experience of depression and anxiety alone. METHOD: A review of the perinatal
      literature was conducted using several databases, to identify studies that have
      focused on the experience of stress as a distinct affective state in the
      perinatal period. FINDINGS: The findings of two recent studies which have
      employed a broader conceptualisation of perinatal distress to encompass the
      experience of stress as well as depression and anxiety are outlined. These recent
      studies have identified the experience of stress both in conjunction with and
      independent of depression and anxiety. CONCLUSION: It is argued that future
      studies should investigate the concept of stress as a separate affective state
      throughout the perinatal period, in order to further assess how it differs from
      depression and/or anxiety. A more comprehensive understanding of women's
      experiences during their transition to motherhood, and whether 'stress' plays a
      critical role in the development and maintenance of perinatal anxiety and/or
      depression is needed.

PMID- 24461689
TI  - Predictors of symptomatic remission in patients with first-episode schizophrenia:
      a 16years follow-up study.
AB  - OBJECTIVE: Recent views on schizophrenia outcome and treatment suggest that
      symptomatic remission is possible, and a definition of remission has been
      proposed by the Remission in Schizophrenia Working Group (RSWG). This study
      evaluated whether patients who achieved remission after several years of illness
      (R) showed psychopathological differences at the onset of their disorder compared
      to non-remitted (NR) patients. METHOD: Forty-eight patients with first-episode
      schizophrenia were evaluated with the Positive and Negative Symptoms Scale
      (PANSS) both at the onset of illness and after a mean period of 16years. Patients
      were defined as R or NR according to the RSWG criteria. RESULTS: Eighteen
      patients (37.5%) were classified as R at follow-up. At onset, R patients showed a
      lower illness severity, less severe negative and general psychopathology symptoms
      compared to NR. Furthermore, they underwent fewer psychotic episodes than NR over
      the course of follow-up. Remission was predicted by lower severity of negative
      and general psychopathology symptoms at onset and by lesser number of psychotic
      episodes during follow-up. CONCLUSIONS: The symptomatic remission may be a viable
      outcome in schizophrenia, particularly for patients with a mild illness and less
      severe negative symptoms at onset and with few psychotic episodes over time.

PMID- 24461690
TI  - A critique of the manuscript: "Distribution and concentrations of petroleum
      hydrocarbons associated with the BP/Deepwater Horizon oil spill, Gulf of Mexico".

PMID- 24461691
TI  - Source apportionment of polycyclic aromatic hydrocarbons in soils of wetlands in
      the Liao River Delta, Northeast China.
AB  - The polycyclic aromatic hydrocarbons (PAHs) of 55 surface soil samples from the
      wetlands in the Liao River Delta, Northeast China were measured in order to
      apportion their sources. The total concentrations of 16 US EPA priority PAHs and
      alkyl-PAHs in this region ranged 106-3148 ng g-1 (dry weight) (average: 550 +/-
      565 ng g-1) and 54-5564 ng g-1 (average: 517 +/- 838 ng g-1), respectively. Based
      on the positive matrix factorization analysis of alkylated and parent PAHs, six
      sources of PAHs were identified including petroleum (23%), biomass burning (23%),
      air-soil exchange (18%), coal combustion (17%), traffic emission (14%) and
      biogenic origin (6%). The positive correlation between low molecular weight (LMW)
      PAHs and TOC contents could demonstrate a potential positive influence of TOC on
      the accumulations of LMW PAHs in soils by the air-soil exchange. The petrogenic
      PAHs may pose a limited harmful effect on aquatic organisms although they were
      abundant in the area.

PMID- 24461692
TI  - Marine Pollution Bulletin. Editorial.

PMID- 24461693
TI  - Variation in organochlorine accumulation in relation to the life history of the
      Japanese eel Anguilla japonica.
AB  - Members of the catadromous eel live in various fresh, brackish and marine
      habitats. Therefore, these eels can accumulate organic pollutants and are a
      suitable bioindicator species for determining the levels of organic contaminants
      within different water bodies. The ecological risk for organochlorine compounds
      (OCs) in Anguilla japonica with various migration patterns, such as freshwater,
      estuarine and marine residences, was examined to understand the specific
      accumulation patterns. The concentrations of HCB, ?HCHs, ?CHLs and ?DDTs in the
      silver stage (maturing) eel were significantly higher than those in the yellow
      stage (immature) eel, in accordance with the higher lipid contents in the former
      versus the latter. The OC accumulations were clearly different among migratory
      types in the eel. The ecological risk of OCs increased as the freshwater
      residence period in the eel lengthened. The migratory histories and the lipid
      contents directly affected the OC accumulation in the catadromous eel species. 

PMID- 24461694
TI  - Detoxification of hazardous dust with marine sediment.
AB  - Hazardous electric arc furnace dust containing dioxins/furans and heavy metals is
      blended with harbor sediment, fired at 950-1100  degrees C to prepare lightweight
      aggregates. Dust addition can lower the sintering temperature by about 100 
      degrees C, as compared to a typical industrial process. After firing at 950 
      degrees C and 1050  degrees C, more than 99.85% of dioxins/furans originally
      present in the dust have been removed and/or destructed in the mix containing a
      dust/sediment ratio of 50:100. The heavy metals leached from all fired mixes are
      far below Taiwan EPA legal limits. The particle density of the lightweight
      aggregates always decreases with increasing firing temperature. Greater addition
      of the dust results in a considerably lower particle density (mostly <2.0 g cm(
      3)) fired at 1050  degrees C and 1100  degrees C. However, firing at temperatures
      lower than 1050  degrees C produces no successful bloating, leading to a denser
      particle density (>2.0 g cm(-3)) that is typical of bricks.

PMID- 24461695
TI  - Occurrence of xenobiotic ligands for retinoid X receptors and thyroid hormone
      receptors in the aquatic environment of Taiwan.
AB  - Various synthetic compounds are frequently discharged into the environment via
      human activities. Among them, certain contaminants may disrupt normal
      physiological functions of wildlife and humans via interactions with nuclear
      receptors. To protect human health and the environment, it is important to detect
      environmental ligands for human nuclear receptors. In this study, yeast-based
      reporter gene assays were used to investigate the occurrence of xenobiotic
      ligands for retinoid X receptors (RXR) and thyroid hormone receptors (TR) in the
      aquatic environment of Taiwan. Experimental results revealed that RXR
      agonist/antagonist activity was detected in river water and sediment samples. In
      particular, high RXR agonist/antagonist activity was found in the samples
      collected near river mouths. Additionally, few samples also elicited significant
      TR antagonist activity. Our findings show that the aquatic environment of Taiwan
      was contaminated with RXR and TR ligands. Further study is necessary to identify
      these xenobiotic RXR and TR agonists and antagonists. 

PMID- 24461696
TI  - The discrepancy in concentration of metals (Cu, Pb and Zn) in oyster tissue
      (Saccostrea glomerata) and ambient bottom sediment (Sydney estuary, Australia).
AB  - The current study aimed to examine the relationship between metals in sediments
      and metal bioaccumulation in oyster tissue in a highly-modified estuary (Sydney
      estuary, Australia). While extensive metal contamination was observed in
      surficial sediments, suspended particulate matter and oyster tissue, a
      significant relationship between these media could not be established. No
      relationship was determined between sediment quality guidelines and oyster size
      or weight, nor with human consumption levels for metals in oyster tissue.
      Moreover, oyster tissue metal concentrations varied greatly at a single locality
      over temporal scales of years. Oyster tissue at all 19 study sites exceeded
      consumptions levels for Cu. Bioaccumulation of metals in oyster tissue is a
      useful dynamic indicator of anthropogenic influence within estuaries, however
      oysters cannot be used in Sydney estuary as a valid biomonitor due to overriding
      internal regulation (homoestasis) by the animal, or by external natural (sediment
      resuspension) and anthropogenic (sewer/stormwater discharges) pressures, or both.

PMID- 24461697
TI  - Contemporary radioecological state of the North-western Black Sea and the
      problems of environment conservation.
AB  - Review is devoted to the analysis of a radioecological situation in the North
      western Black Sea and concerns the levels of contamination of the components of
      an ecosystem by the main artificial radioactive isotopes ((90)Sr, (137)Cs,
      (239,240)Pu). The long-term accumulation trends of these radionuclides were
      analyzed in components of the Black Sea ecosystem after the Chernobyl nuclear
      power plant accident. Zones that have an increased ability to accumulate these
      radioisotopes were revealed. The assessment of irradiation dose rates formed by
      (90)Sr, (137)Cs and (239,240)Pu in Black Sea hydrobionts was obtained. The
      strategy for biodiversity conservation and sustainable management of natural
      resources should include monitoring of the radioecological state of the marine
      ecosystems, and the formation of a complex of biogeochemical criteria for
      assessment of an ecological situation in the sea. This approach is important for
      marine protected areas, since it allows the formation of a basis for scientific
      and practical function. 

PMID- 24461698
TI  - Minimal incorporation of Deepwater Horizon oil by estuarine filter feeders.
AB  - Natural abundance carbon isotope analyses are sensitive tracers for fates and use
      of oil in aquatic environments. Use of oil carbon in estuarine food webs should
      lead to isotope values approaching those of oil itself, -270/00 for stable carbon
      isotopes reflecting oil origins and -10000/00 for carbon-14 reflecting oil age.
      To test for transfer of oil from the 2010 Deepwater Horizon spill into estuarine
      food webs, filter-feeding barnacles (Balanus sp.) and marsh mussels (Geukensia
      demissa) were collected from Louisiana estuaries near the site of the oil spill.
      Carbon-14 analyses of these animals from open waters and oiled marshes showed
      that oil use was <1% and near detection limits estimated at 0.3% oil
      incorporation. Respiration studies showed no evidence for enhanced microbial
      activity in bay waters. Results are consistent with low dietary impacts of oil
      for filter feeders and little overall impact on respiration in the productive
      Louisiana estuarine systems. 

PMID- 24461699
TI  - Spatial variability of total dissolved copper and copper speciation in the
      inshore waters of Bermuda.
AB  - Total dissolved copper (Cu) and Cu speciation were examined from inshore waters
      of Bermuda, in October 2009 and July-August 2010, to determine the relationship
      between total dissolved Cu, Cu-binding ligands and bioavailable, free, hydrated
      Cu(2+) concentrations. Speciation was performed using competitive ligand exchange
      adsorptive cathodic stripping voltammetry (CLE-ACSV). Mean total dissolved Cu
      concentrations ranged from 1.4 nM to 19.2 nM, with lowest concentrations at sites
      further from shore, consistent with previous measurements in the Sargasso Sea,
      and localized Cu enrichment inshore in enclosed harbors. Ligand concentrations
      exceeded dissolved [Cu] at most sites, and [Cu(2+)] were correspondingly low at
      those sites, typically <10(-13) M. One site, Hamilton Harbour, was found to have
      [Cu] in excess of ligands, resulting in [Cu(2+)] of 10(-10.7) M, and indicating
      that Cu may be toxic to phytoplankton here.

PMID- 24461700
TI  - Organochlorine pesticide content and distribution in coastal seafoods in
      Zhoushan, Zhejiang Province.
AB  - Thirteen types of seafoods were collected from four counties (districts) of
      Zhoushan, Zhejiang Province, China and analyzed for organochlorine pesticides
      (OCPs). The average concentrations of OCPs in seafoods ranged from 258.3 ng g-1
      (lw) to 3459.6 ng g-1 (lw). Hexachlorocyclohexanes (HCHs) and
      dichlorodiphenyltrichloroethanes (DDTs) were the most abundant compounds in these
      environments and in total accounted for 8.2-62.2% and 32.1-89.0% of the total
      OCPs in seafoods, respectively. The total OCP contents were higher in seafoods
      from Shengsi and Putuo and lower in those from Dinghai and Daishan. The ratios of
      (DDE+DDD)/DDTs reflected a mixed input of accumulated and fresh DDTs in Shengsi,
      Putuo. The ratios of o,p'-DDT/p,p'-DDT in seafoods of Shengsi ranged 0.10-0.60
      (mean 0.33), indicating that DDTs in seafoods of Shengsi may partly contain
      dicofol products and other pollutants accumulated in Yangtze Estuary. DDTs are a
      greater concern for ecotoxicological risk in the study area.

PMID- 24461701
TI  - Monitoring red tide with satellite imagery and numerical models: a case study in
      the Arabian Gulf.
AB  - A red tide event that occurred in August 2008 in the Arabian Gulf was monitored
      and assessed using satellite observations and numerical models. Satellite
      observations revealed the bloom extent and evolution from August 2008 to August
      2009. Flow patterns of the bloom patch were confirmed by results from a HYCOM
      model. HYCOM data and satellite-derived sea surface temperature data further
      suggested that the bloom could have been initiated offshore and advected onshore
      by bottom Ekman layer. Analysis indicated that nutrient sources supporting the
      bloom included upwelling, Trichodesmium, and dust deposition while other
      potential sources of nutrient supply should also be considered. In order to
      monitor and detect red tide effectively and provide insights into its initiation
      and maintenance mechanisms, the integration of multiple platforms is required.
      The case study presented here demonstrated the benefit of combing satellite
      observations and numerical models for studying red tide outbreaks and dynamics. 

PMID- 24461702
TI  - Electroporation of archaeal lipid membranes using MD simulations.
AB  - Molecular dynamics (MD) simulations were used to investigate the electroporation
      of archaeal lipid bilayers when subjected to high transmembrane voltages induced
      by a charge imbalance, mimicking therefore millisecond electric pulse
      experiments. The structural characteristics of the bilayer, a 9:91 mol% 2,3-di-O
      sesterterpanyl-sn-glicerol-1-phospho-myo-inositol (AI) and 2,3-di-O
      sesterterpanyl-sn-glicerol-1-phospho-1'(2'-O-alpha-D-glucosyl)-myo-inositol (AGI)
      were compared to small angle X-ray scattering data. A rather good agreement of
      the electron density profiles at temperatures of 298 and 343 K was found
      assessing therefore the validity of the protocols and force fields used in
      simulations. Compared to dipalmitoyl-phosphatidylcholine (DPPC), the
      electroporation threshold for the bilayer was found to increase from ~2 V to 4.3
      V at 323 K, and to 5.2 V at 298 K. Comparing the electroporation thresholds of
      the archaeal lipids to those of simple diphytanoyl-phosphatidylcholine (DPhPC)
      bilayers (2.5 V at 323 K) allowed one to trace back the stability of the
      membranes to the structure of their lipid head groups. Addition of DPPC in
      amounts of 50 mol% to the archaeal lipid bilayers decreases their stability and
      lowers the electroporation thresholds to 3.8 V and 4.1 V at respectively 323 and
      298 K. The present study therefore shows how membrane compositions can be
      selected to cover a wide range of responses to electric stimuli. This provides
      new routes for the design of liposomes that can be efficiently used as drug
      delivery carriers, as the selection of their composition allows one to tune in
      their electroporation threshold for subsequent release of their load.

PMID- 24461703
TI  - Positive nuclear expression of KLF8 might be correlated with shorter survival in
      gastric adenocarcinoma.
AB  - Kruppel-like factor 8 (KLF8) is important in cell proliferation, epithelial-to
      mesenchymal transition, cell migration, and invasion. Gastric adenocarcinoma is
      among the leading causes of cancer-related death in the world. In this study, the
      clinicopathologic correlation of KLF8 expression with gastric adenocarcinoma in
      Taiwan was investigated. The nuclear localization of KLF8 was correlated with
      advanced stage (P = .008) and 3-year survival rate (P = .043). The nuclear
      expression of KLF8 was significantly higher in the diffused type of gastric
      adenocarcinoma compared with the intestinal type (P = .036). Kaplan-Meier
      analysis results showed that patients with positive nuclear KLF8 had
      significantly lower overall survival rate compared with those with negative
      nuclear KLF8 (P = .011). Univariate analysis results indicated that positive
      nuclear KLF8 expression, advanced stage, and lymph node metastasis are correlated
      with lower overall survival. Positive nuclear KLF8 might be correlated with lower
      survival in gastric adenocarcinoma patients and might be an oncogene property in
      gastric adenocarcinoma carcinogenesis. 

PMID- 24461704
TI  - Microscopic intraneural perineurial cell proliferations in patients with
      neurofibromatosis type 1.
AB  - Benign peripheral nerve sheath tumors (PNSTs) showing more than one line of
      differentiation (hybrid PNSTs) have been increasingly recognized, mainly due to
      awareness of their existence and as a consequence of increased use of
      immunohistochemisty during the last decade. Two recent studies suggested
      overrepresentation of hybrid tumors among benign PNSTs in patients with
      neurofibromatosis type 1 (NF-1). This study was performed to assess the presence
      of perineurial cells in microscopic (early) neurofibromatous lesions and normal
      looking peripheral nerves in specimens from 5 patients with NF-1 using markers of
      perineurial cell differentiation (epithelial membrane antigen, claudin-1, and
      glucose transporter 1). In 2 patients, multiple normal looking nerve fibers as
      well as hypertrophied nerves and microscopic tumor nodules showed variable
      intraneural perineurial cell proliferations that frequently occupied the whole
      nerve fascicle resulting in multiple microscopic reticular perineurioma-like
      nodules (microscopic hybrid neurofibromatosis/perineuriomatosis). None of the
      cases showed the onion skin pattern of intraneural perineurioma. However, other
      nerve fibers within the same specimens showed normal compact rim of perineurium
      without any detectable intraneural perineurial cells. Both patients had
      concurrent multiple larger PNSTs (plexiform neurofibromas, hybrid
      neurofibroma/perineurioma and lesions with features intermediate between the 2
      types). One specimen harboring high-grade malignant PNST and 2 specimens with
      large solitary neurofibromas displayed no intraneural perineurial cells. These
      observations suggest that intraneural perineurial proliferations are part of the
      early lesions in the setting of constitutional NF-1 inactivation and support the
      concept of pure and hybrid perineuriomatous lesions as novel member of the
      spectrum of PNSTs in NF-1. 

PMID- 24461705
TI  - [The early diagnosis of human immunodeficiency virus infection in the emergency
      department].

PMID- 24461706
TI  - A region-based anatomical landmark configuration for sinus surgery using image
      guided navigation system: a phantom-study.
AB  - PURPOSE: To evaluate the current beliefs about the ways to reduce target
      registration error (TRE) values in image guided Sinus surgery by rearranging the
      fiducial configuration, and investigating the best configurations for various
      surgical fields in a phantom study. METHODS: A new CT-compatible skull phantom
      consisting of implanted targets was designed to enable direct measurement of TRE
      in four fields of sinus surgery, Frontal, Ethmoid, Sphenoid and Maxillary. The
      effects of different landmark configurations on TRE values, measured by the
      Parsiss-IV navigation system were investigated to find the best landmark
      arrangement for each region, and compared to the TRE prediction formula to assess
      the clinically accepted landmark selection approaches based on this formula.
      RESULTS: It was shown that smaller values of TRE could be attained by arranging
      the center of the fiducials to be more focused on the surgery target. The
      addition of more fiducials and keeping non-linear arrangement of landmark would
      not necessarily decrease the TRE value. CONCLUSION: Optimizing the landmark
      configuration is important for increasing the localization accuracy in image
      guided sinus surgery. The common beliefs accepted in the clinical community about
      the ways to reduce the TRE are very general and should be adapted to specific
      field of image guided surgery.

PMID- 24461707
TI  - Options in improving respiratory function in multiple sclerosis.

PMID- 24461708
TI  - Depression and spinal cord injury.

PMID- 24461710
TI  - In vitro activity of rifaximin against isolates from patients with small
      intestinal bacterial overgrowth.
AB  - Rifaximin, a non-absorbable rifamycin derivative, has published clinical efficacy
      in the alleviation of symptoms in patients with irritable bowel syndrome (IBS).
      Small intestinal bacterial overgrowth (SIBO) is associated with the pathogenesis
      of IBS. This study describes for the first time the antimicrobial effect of
      rifaximin against SIBO micro-organisms from humans. Fluid was aspirated from the
      third part of the duodenum from 567 consecutive patients; quantitative cultures
      diagnosed SIBO in 117 patients (20.6%). A total of 170 aerobic micro-organisms
      were isolated and the in vitro efficacy of rifaximin was studied by (i) minimum
      inhibitory concentration (MIC) testing by a microdilution technique and (ii) time
      kill assays using bile to simulate the small intestinal environment. At a
      breakpoint of 32 MUg/mL, rifaximin inhibited in vitro 85.4% of Escherichia coli,
      43.6% of Klebsiella spp., 34.8% of Enterobacter spp., 54.5% of other
      Enterobacteriaceae spp., 82.6% of non-Enterobacteriaceae Gram-negative spp., 100%
      of Enterococcus faecalis, 100% of Enterococcus faecium and 100% of Staphylococcus
      aureus. For the time-kill assays, 11 E. coli, 15 non-E. coli Gram-negative
      enterobacteria and three E. faecalis isolates were studied. Rifaximin produced a
      >3 log10 decrease in the starting inoculum against most of the tested isolates at
      500 MUg/mL after 24h of growth. The results indicate that rifaximin has a potent
      effect on specific small bowel flora associated with SIBO. This conclusion should
      be regarded in light of the considerable time-kill effect at concentrations lower
      than those achieved in the bowel lumen after administration of conventional doses
      in humans.

PMID- 24461709
TI  - Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC
      class II expression and capable of inciting an immune response in vitro.
AB  - INTRODUCTION: The horse is a valuable species to assess the effect of allogeneic
      mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date
      have examined recipient response to major histocompatibility complex (MHC)
      mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs
      from horses of known MHC haplotype and to compare the immunogenicity of MSCs with
      differing MHC class II expression. METHODS: MSCs and peripheral blood leukocytes
      (PBLs) were obtained from Thoroughbred horses (n=10) of known MHC haplotype (ELA
      A2, -A3, and -A9 homozygotes). MSCs were cultured through P8; cells from each
      passage (P2 to P8) were cryopreserved until used. Immunophenotyping of MHC class
      I and II, CD44, CD29, CD90, LFA-1, and CD45RB was performed by using flow
      cytometry. Tri-lineage differentiation assays were performed to confirm MSC
      multipotency. Recombinant equine IFN-gamma was used to stimulate MHC class II
      negative MSCs in culture, after which expression of MHC class II was re-examined.
      To assess the ability of MHC class II negative or positive MSCs to stimulate an
      immune response, modified one-way mixed leukocyte reactions (MLRs) were performed
      by using MHC-matched and mismatched responder PBLs and stimulator PBLs or MSCs.
      Proliferation of gated CFSE-labeled CD3+ responder T cells was evaluated via CFSE
      attenuation by using flow cytometry and reported as the number of cells in the
      proliferating T-cell gate. RESULTS: MSCs varied widely in MHC class II expression
      despite being homogenous in terms of "stemness" marker expression and ability to
      undergo trilineage differentiation. Stimulation of MHC class II negative MSCs
      with IFN-gamma resulted in markedly increased expression of MHC class II. MLR
      results revealed that MHC-mismatched MHC class II-positive MSCs caused
      significantly increased responder T-cell proliferation compared with MHC
      mismatched MHC class II-negative and MHC-matched MSCs, and equivalent to that of
      the positive control of MHC-mismatched leukocytes. CONCLUSIONS: The results of
      this study suggest that MSCs should be confirmed as MHC class II negative before
      allogeneic application. Additionally, it must be considered that even MHC class
      II-negative MSCs could upregulate MHC class II expression if implanted into an
      area of active inflammation, as demonstrated with in vitro stimulation with IFN
      gamma.

PMID- 24461711
TI  - Application of nucleic acid-lipid conjugates for the programmable organisation of
      liposomal modules.
AB  - We present a critical review of recent work related to the assembly of
      multicompartment liposome clusters using nucleic acids as a specific recognition
      unit to link liposomal modules. The asymmetry in nucleic acid binding to its non
      self complementary strand allows the controlled association of different
      compartmental modules into composite systems. These biomimetic multicompartment
      architectures could have future applications in chemical process control, drug
      delivery and synthetic biology. We assess the different methods of anchoring DNA
      to lipid membrane surfaces and discuss how lipid and DNA properties can be tuned
      to control the morphology and properties of liposome superstructures. We consider
      different methods for chemical communication between the contents of liposomal
      compartments within these clusters and assess the progress towards making this
      chemical mixing efficient, switchable and chemically specific. Finally, given the
      current state of the art, we assess the outlook for future developments towards
      functional modular networks of liposomes. 

PMID- 24461712
TI  - Evidence for the existence of two new members of the family Chlamydiaceae and
      proposal of Chlamydia avium sp. nov. and Chlamydia gallinacea sp. nov.
AB  - The family Chlamydiaceae with the recombined single genus Chlamydia currently
      comprises nine species, all of which are obligate intracellular organisms
      distinguished by a unique biphasic developmental cycle. Anecdotal evidence from
      epidemiological surveys in flocks of poultry, pigeons and psittacine birds have
      indicated the presence of non-classified chlamydial strains, some of which may
      act as pathogens. In the present study, phylogenetic analysis of ribosomal RNA
      and ompA genes, as well as multi-locus sequence analysis of 11 field isolates
      were conducted. All independent analyses assigned the strains into two different
      clades of monophyletic origin corresponding to pigeon and psittacine strains or
      poultry isolates, respectively. Comparative genome analysis involving the type
      strains of currently accepted Chlamydiaceae species and the designated type
      strains representing the two new clades confirmed that the latter could be
      classified into two different species as their average nucleotide identity (ANI)
      values were always below 94%, both with the closest relative species and between
      themselves. In view of the evidence obtained from the analyses, we propose the
      addition of two new species to the current classification: Chlamydia avium sp.
      nov. comprising strains from pigeons and psittacine birds (type strain 10DC88(T);
      DSMZ: DSM27005(T), CSUR: P3508(T)) and Chlamydia gallinacea sp. nov. comprising
      strains from poultry (type strain 08-1274/3(T); DSMZ: DSM27451(T), CSUR:
      P3509(T)). 

PMID- 24461713
TI  - Phylogeny of culturable cyanobacteria from Brazilian mangroves.
AB  - The cyanobacterial community from Brazilian mangrove ecosystems was examined
      using a culture-dependent method. Fifty cyanobacterial strains were isolated from
      soil, water and periphytic samples collected from Cardoso Island and Bertioga
      mangroves using specific cyanobacterial culture media. Unicellular, homocytous
      and heterocytous morphotypes were recovered, representing five orders, seven
      families and eight genera (Synechococcus, Cyanobium, Cyanobacterium, Chlorogloea,
      Leptolyngbya, Phormidium, Nostoc and Microchaete). All of these novel mangrove
      strains had their 16S rRNA gene sequenced and BLAST analysis revealed sequence
      identities ranging from 92.5 to 99.7% when they were compared with other strains
      available in GenBank. The results showed a high variability of the 16S rRNA gene
      sequences among the genotypes that was not associated with the morphologies
      observed. Phylogenetic analyses showed several branches formed exclusively by
      some of these novel 16S rRNA gene sequences. BLAST and phylogeny analyses allowed
      for the identification of Nodosilinea and Oxynema strains, genera already known
      to exhibit poor morphological diacritic traits. In addition, several Nostoc and
      Leptolyngbya morphotypes of the mangrove strains may represent new generic
      entities, as they were distantly affiliated with true genera clades. The presence
      of non-ribosomal peptide synthetase, polyketide synthase, microcystin and
      saxitoxin genes were detected in 20.5%, 100%, 37.5% and 33.3%, respectively, of
      the 44 tested isolates. A total of 134 organic extracts obtained from 44 strains
      were tested against microorganisms, and 26% of the extracts showed some
      antimicrobial activity. This is the first polyphasic study of cultured
      cyanobacteria from Brazilian mangrove ecosystems using morphological, genetic and
      biological approaches. 

PMID- 24461714
TI  - Genetic diversity of root nodulating bacteria associated with Retama sphaerocarpa
      in sites with different soil and environmental conditions.
AB  - The genetic diversity of root nodulating bacteria isolated from Retama
      sphaerocarpa was studied using BOX-A1R PCR and phylogenetic analysis of the 16S
      rRNA region, as well as the housekeeping genes atpD, glnII and recA. A total of
      193 isolates were obtained from eight different sites with different soil and
      environmental conditions in the Iberian Peninsula. These isolates corresponded to
      31 different strains that successfully nodulated R. sphaerocarpa seedlings in
      reinoculation trials. About one-third of the strains clustered with B. canariense
      or B. cytisi within Bradyrhizobium group I. The remaining strains clustered with
      B. elkanii/B. pachyrhizi within Bradyrhizobium group II or in separate clades
      that could represent new lineages. Based on the 16S rRNA and combined
      atpD+glnII+recA sequences, two to three lineages of root nodulating bacteria were
      found at each sampling site, except for Collado Garcia where five species were
      detected. B. canariense and B. elkanii/B. pachyrhizi were the most abundant
      species, whereas the least abundant were those related to B. retamae and a
      putative new lineage. B. canariense was found only in soils with neutral and acid
      pH, whereas B. retamae was the dominant species in alkaline soils. 

PMID- 24461716
TI  - International comparisons of acute myocardial infarction.

PMID- 24461715
TI  - Acute myocardial infarction: a comparison of short-term survival in national
      outcome registries in Sweden and the UK.
AB  - BACKGROUND: International research for acute myocardial infarction lacks
      comparisons of whole health systems. We assessed time trends for care and
      outcomes in Sweden and the UK. METHODS: We used data from national registries on
      consecutive patients registered between 2004 and 2010 in all hospitals providing
      care for acute coronary syndrome in Sweden and the UK. The primary outcome was
      all-cause mortality 30 days after admission. We compared effectiveness of
      treatment by indirect casemix standardisation. This study is registered with
      ClinicalTrials.gov, number NCT01359033. FINDINGS: We assessed data for 119,786
      patients in Sweden and 391,077 in the UK. 30-day mortality was 7.6% (95% CI 7.4
      7.7) in Sweden and 10.5% (10.4-10.6) in the UK. Mortality was higher in the UK in
      clinically relevant subgroups defined by troponin concentration, ST-segment
      elevation, age, sex, heart rate, systolic blood pressure, diabetes mellitus
      status, and smoking status. In Sweden, compared with the UK, there was earlier
      and more extensive uptake of primary percutaneous coronary intervention (59% vs
      22%) and more frequent use of beta blockers at discharge (89% vs 78%). After
      casemix standardisation the 30-day mortality ratio for UK versus Sweden was 1.37
      (95% CI 1.30-1.45), which corresponds to 11,263 (95% CI 9620-12,827) excess
      deaths, but did decline over time (from 1.47, 95% CI 1.38-1.58 in 2004 to 1.20,
      1.12-1.29 in 2010; p=0.01). INTERPRETATION: We found clinically important
      differences between countries in acute myocardial infarction care and outcomes.
      International comparisons research might help to improve health systems and
      prevent deaths. FUNDING: Seventh Framework Programme for Research, National
      Institute for Health Research, Wellcome Trust (UK), Swedish Association of Local
      Authorities and Regions, Swedish Heart-Lung Foundation.

PMID- 24461717
TI  - Evaluation of full costs of care for patients with Alzheimer's disease in France:
      the predominant role of informal care.
AB  - OBJECTIVE: It is crucial that the cost of Alzheimer's disease be evaluated, from
      a societal perspective, since the number of patients is expected to increase
      dramatically in the coming decades. This assessment of the full cost of care for
      community-dwelling patients with Alzheimer's disease in France also addresses the
      factors associated with informal care, its predominant component. DATA AND
      METHODS: From 2009 to 2010, 57 patient/informal caregiver pairs were interviewed
      using the Resource Utilization in Dementia questionnaire, adapted to provide a
      micro-costing approach of the overall care process. Both the opportunity cost
      method and the proxy good method were used to value informal care. Ordinary least
      square regression was performed to determine factors associated with informal
      care. RESULTS: Average total monthly costs were ?2450 with the proxy good method
      and ?3102 with the opportunity cost method. Living with the patient, severity of
      dementia and hours spent on formal care were significantly associated with
      informal care time. POLICY IMPLICATIONS: Since French allowance cannot cover all
      formal and informal non-medical costs, the choice for policy makers is either to
      spend more on formal care or to develop family care by investing in supportive
      programmes for informal caregivers.

PMID- 24461718
TI  - Evaluation of health care delivery integration: the case of the Russian
      Federation.
AB  - Fragmentation in organization and discontinuities in the provision of medical
      care are problems in all health systems, whether it is the mixed public-private
      one in the USA, national health services in the UK, or insurance based one in
      Western Europe and Russia. In all of these countries a major challenge is to
      strengthen integration in order to enhance efficiency and health outcomes. This
      article assesses issues related to fragmentation and integration in conceptual
      terms and argues that key attributes of integration are teamwork, coordination
      and continuity of care. It then presents a summary of service integration
      problems in Russia and the results of a large survey of physicians concerning the
      attributes of integration. It is argued that characteristics of the national
      service delivery model don't ensure integration. The Semashko model is not an
      equivalent to the integrated model. Big organizational forms of service
      provision, like polyclinics and integrated hospital-polyclinics, don't have
      higher scores of integration indicators than smaller ones. Proposals to improve
      integration in Russia are presented with the focus on the regular evaluation of
      integration/fragmentation, regulation of integration activities, enhancing the
      role of PHC providers, economic incentives. 

PMID- 24461719
TI  - Task shifting policy in Ontario, Canada: does it help personal support workers'
      intention to stay?
AB  - The objective of this paper is to analyze the impact of task shifting policy on
      personal support workers' (PSWs) intention to stay in home care. Data were
      collected through interviews with 46 home care staff of a large home care
      organization in Ontario, Canada. Interviews were transcribed, coded, and a
      thematic analysis was conducted using a qualitative software package. Half of the
      study participants mentioned that task shifting increases PSWs' intention to stay
      in home care, while less than a quarter commented that task shifting increases
      PSWs intention to leave. Results show that the implementation of task shifting
      policy in Ontario, Canada may contribute to personal support workers' intention
      to stay; however, inadequate compensation may negatively affect intention to stay
      and should be addressed. We recommend policy-makers consider appropriate
      compensation to assist PSWs in effectively executing shifted tasks. 

PMID- 24461720
TI  - [Peripheral arterial disease and cardiovascular risk factors among patients
      infected with human immunodeficiency virus: a comparison between hospital out
      patients and patients in a prison].
AB  - INTRODUCTION: Cardiovascular disease among human immunodeficiency virus (HIV)
      infected patients is more frequent than in the general population. Peripheral
      arterial disease measured by ankle-brachial index (ABI) and cardiovascular risk
      factors (CVRF) is not well known in all groups of HIV-infected patients. METHODS:
      Transversal study of HIV-infected patients >45 years, seen as outpatients in
      hospital (HO) in 2008 and patients institutionalized in a prison in 2009.
      Cardiovascular risk factors, information on the HIV infection and healthy
      lifestyles were evaluated. ABI was measured at rest and was considered
      pathological when a value <= 0.9 or >= 1.3 was obtained. RESULTS: We included 71
      patients (mean age of 50.6 +/- 6.9 years, 86% male), 32 HO and 39 in prison. The
      most prevalent CVRF was smoking (80.2%) followed by an altered lipid profile
      (63.3%). The evolution time of HIV infection was 13.1 +/- 7.1 years. 74.6% of
      patients didn't follow a heart-healthy diet and 25% were sedentary. The ABI was
      low in 7 cases (9.8%) and >= 1.3 in one. Patients in prison were younger, the
      rate of smokers and of individuals with low HDL were higher, the time of
      evolution of the HIV infections was longer and they were less adherent to a heart
      healthy diet than in HO, reaching in all cases statistical significance (P<.05).
      CONCLUSIONS: In our study there is a high prevalence of altered ABI. The most
      common CVRF is smoking, followed by the alteration of lipids. Patients in prison
      are more likely to be smokers, to have low HDL and they are less adherence to a
      heart-healthy diet.

PMID- 24461721
TI  - SMAD3 gene variant is a risk factor for recurrent surgery in patients with
      Crohn's disease.
AB  - BACKGROUND AND AIMS: More than 80% of Crohn's disease (CD) patients will require
      surgery. Surgery is not curative and rates of re-operation are high.
      Identification of genetic variants associated with repeat surgery would allow
      risk stratification of patients who may benefit from early aggressive therapy
      and/or post-operative prophylactic treatment. METHODS: CD patients who had at
      least one CD-related bowel resection were identified from the Prospective
      Registry in IBD Study at Massachusetts General Hospital (PRISM). The primary
      outcome was surgical recurrence. Covariates and potential interactions were
      assessed using the Cox proportional hazard model. Kaplan-Meier curves for time to
      surgical recurrence were developed for each genetic variant and analyzed with the
      log-rank test. RESULTS: 194 patients were identified who had at least 1
      resection. Of these, 69 had two or more resections. Clinical predictors for
      repeat surgery were stricturing (HR 4.18, p=0.022) and penetrating behavior (HR
      3.97, p=0.024). Smoking cessation was protective for repeat surgery (HR 0.45,
      p=0.018). SMAD3 homozygosity for the risk allele was also independently
      associated with increased risk of repeat surgery (HR 4.04, p=0.001). NOD2 was not
      associated with increased risk of surgical recurrence. CONCLUSION: Stricturing
      and penetrating behavior were associated with increased risk of surgical
      recurrence, while smoking cessation was associated with a decreased risk. A novel
      association between SMAD3 and increased risk of repeat operation and shorter time
      to repeat surgery was observed. This finding is of particular interest as SMAD3
      may represent a new therapeutic target specifically for prevention of post
      surgical disease recurrence.

PMID- 24461722
TI  - Functional characterisation of bovine TLR5 indicates species-specific recognition
      of flagellin.
AB  - Mammalian toll-like receptor 5 (TLR5) senses flagellin of several bacterial
      species and has been described to activate the innate immune system. To assess
      the role of bovine TLR5 (boTLR5) in the cattle system, we cloned and successfully
      expressed boTLR5 in human embryonic kidney (HEK) 293 cells, as indicated by
      quantitative PCR and confocal microscopy. However, in contrast to huTLR5
      transfected cells, exposure of boTLR5-transfected cells to flagellin neither
      activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF
      kappaB) nor CXCL8 production. Subsequent comparison of the flagellin response
      induced in human and bovine primary macrophages revealed that flagellin did not
      lead to phosphorylation of major signalling molecules. Furthermore, the CXCL8 and
      TNFalpha response of primary bovine macrophages stimulated with flagellin was
      very low compared to that observed in human primary macrophages. Our results
      indicate that cattle express a functional TLR5 albeit with different flagellin
      sensing qualities compared to human TLR5. However, boTLR5 seemed to play a
      different role in the bovine system compared to the human system in recognizing
      flagellin, and other potentially intracellular expressed receptors may play a
      more important role in the bovine system to detect flagellin. 

PMID- 24461723
TI  - Neuropeptide Y in the central nucleus of amygdala regulates the anxiolytic effect
      of agmatine in rats.
AB  - In the present study, modulation of anxiolytic action of agmatine by neuropeptide
      Y (NPY) in the central nucleus of amygdala (CeA) is evaluated employing Vogel's
      conflict test (VCT) in rats. The intra-CeA administration of agmatine (0.6 and
      1.2umol/rat), NPY (10 and 20pmol/rat) or NPY Y1/Y5 receptors agonist [Leu(31),
      Pro(34)]-NPY (30 and 60pmol/rat) significantly increased the number of punished
      drinking licks following 15min of treatment. Combination treatment of
      subeffective dose of NPY (5pmol/rat) or [Leu(31), Pro(34)]-NPY (15pmol/rat) and
      agmatine (0.3umol/rat) produced synergistic anxiolytic-like effect. However,
      intra-CeA administration of selective NPY Y1 receptor antagonist, BIBP3226 (0.25
      and 0.5mmol/rat) produced anxiogenic effect. In separate set of experiment,
      pretreatment with BIBP3226 (0.12mmol/rat) reversed the anxiolytic effect of
      agmatine (0.6umol/rat). Furthermore, we evaluated the effect of intraperitoneal
      injection of agmatine (40mg/kg) on NPY-immunoreactivity in the nucleus accumbens
      shell (AcbSh), lateral part of bed nucleus of stria terminalis (BNSTl) and CeA.
      While agmatine treatment significantly decreased the fibers density in BNSTl,
      increase was noticed in AcbSh. In addition, agmatine reduced NPY-immunoreactive
      cells in the AcbSh and CeA. Immunohistochemical data suggest the enhanced
      transmission of NPY from the AcbSh and CeA. Taken together, this study suggests
      that agmatine produced anxiolytic effect which might be regulated via modulation
      of NPYergic system particularly in the CeA. 

PMID- 24461725
TI  - Attitudes toward death, dying, end-of-life palliative care, and interdisciplinary
      practice in long term care workers.
AB  - BACKGROUND: Besides personal and professional experiences, long term care
      providers' own attitudes toward death may affect the care given to dying
      residents. OBJECTIVES: To assess beliefs, values, and attitudes toward death,
      dying, palliative, and interdisciplinary care in long term care workers and
      identify any differences between different job categories and places of work.
      DESIGN: Descriptive cross-sectional survey study. SETTING: Five public long term
      care facilities. PARTICIPANTS: One thousand one hundred seventy volunteers,
      clinical managers, and all categories of residential long term care workers.
      MEASUREMENTS AND METHODS: An anonymous paper or electronic self-administered
      survey questionnaire consisting of 24 items, answered on a 4-point bipolar Likert
      scale. Between-group differences were compared with the analysis of variance test
      after adjustment for the multiple post-hoc comparisons. RESULTS: Healthcare
      workers had a relatively positive attitude toward more than one-half of the
      selected aspects of interdisciplinary practice and end-of-life palliative care
      for long-term residents. However, attitudes were more mixed about 10 other
      aspects and a higher percentage of respondents indicated negative attitudes
      toward them. Overall, there are significant differences between upper-level
      professionals and managers (registered nurses, physicians, rehabilitation staff,
      and clinical managers) vs the hands-on caregivers (nursing assistants, patient
      assistants, and volunteers) with regard to some aspects of the care of the dying.
      CONCLUSIONS: The results suggest that healthcare workers' attitudes need to be
      taken into account in long term care facilities. Patient assistants, volunteers,
      and nursing assistants seem most likely to above all benefit from training and
      support programs.

PMID- 24461726
TI  - Frontiers in diabetic kidney disease: introduction.

PMID- 24461724
TI  - The motivation and pleasure dimension of negative symptoms: neural substrates and
      behavioral outputs.
AB  - A range of emotional and motivation impairments have long been clinically
      documented in people with schizophrenia, and there has been a resurgence of
      interest in understanding the psychological and neural mechanisms of the so
      called "negative symptoms" in schizophrenia, given their lack of treatment
      responsiveness and their role in constraining function and life satisfaction in
      this illness. Negative symptoms comprise two domains, with the first covering
      diminished motivation and pleasure across a range of life domains and the second
      covering diminished verbal and non-verbal expression and communicative output. In
      this review, we focus on four aspects of the motivation/pleasure domain,
      providing a brief review of the behavioral and neural underpinnings of this
      domain. First, we cover liking or in-the-moment pleasure: immediate responses to
      pleasurable stimuli. Second, we cover anticipatory pleasure or wanting, which
      involves prediction of a forthcoming enjoyable outcome (reward) and feeling
      pleasure in anticipation of that outcome. Third, we address motivation, which
      comprises effort computation, which involves figuring out how much effort is
      needed to achieve a desired outcome, planning, and behavioral response. Finally,
      we cover the maintenance emotional states and behavioral responses. Throughout,
      we consider the behavioral manifestations and brain representations of these four
      aspects of motivation/pleasure deficits in schizophrenia. We conclude with
      directions for future research as well as implications for treatment. 

PMID- 24461727
TI  - Glycemic management in ESRD and earlier stages of CKD.
AB  - The management of hyperglycemia in patients with kidney failure is complex, and
      the goals and methods regarding glycemic control in chronic kidney disease (CKD)
      are not clearly defined. Although aggressive glycemic control seems to be
      advantageous in early diabetic nephropathy, outcome data supporting tight
      glycemic control in patients with advanced CKD (including end-stage renal disease
      [ESRD]) are lacking. Challenges in the management of such patients include
      therapeutic inertia, monitoring difficulties, and the complexity of available
      treatments. In this article, we review the alterations in glucose homeostasis
      that occur in kidney failure, current views on the value of glycemic control and
      issues with its determination, and more recent approaches to monitor or measure
      glycemic control. Hypoglycemia and treatment options for patients with diabetes
      and ESRD or earlier stages of CKD also are addressed, discussing the insulin and
      noninsulin agents that currently are available, along with their indications and
      contraindications. The article provides information to help clinicians in
      decision making in order to provide individualized glycemic goals and appropriate
      therapy for patients with ESRD or earlier stages of CKD. 

PMID- 24461728
TI  - Clinical challenges in diagnosis and management of diabetic kidney disease.
AB  - Diabetic kidney disease (DKD) is a major and increasing worldwide public health
      issue. There is a great need for implementing treatments that either prevent or
      significantly slow the progression of DKD. Although there have been significant
      improvements in management, the increasing numbers of patients with DKD
      illustrate that current management is not wholly adequate. The reasons for
      suboptimal management include the lack of early diagnosis, lack of aggressive
      interventions, and lack of understanding about which interventions are most
      successful. There are a number of challenges and controversies regarding the
      current management of patients with DKD. Understanding of these issues is needed
      in order to provide the best care to patients with DKD. This article describes
      some of the clinically important challenges associated with DKD: the current
      epidemiology and cost burden and the role of biopsy in the diagnosis of DKD.
      Treatment controversies regarding current pharmacologic and nonpharmacologic
      approaches are reviewed and recommendations based on the published literature are
      made. 

PMID- 24461729
TI  - Markers of and risk factors for the development and progression of diabetic
      kidney disease.
AB  - Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given
      the dual problems of a significant risk of progression from DKD to end-stage
      renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is
      important to identify patients at risk of DKD and ESRD and initiate protective
      renal and cardiovascular therapies. The importance of preventive therapy is
      emphasized further by worldwide increases in the incidence of diabetes. This
      review summarizes the evidence regarding the prognostic value and benefits of
      targeting established and novel risk markers for DKD development and progression.
      Family history of DKD, smoking history, and glycemic, blood pressure, and plasma
      lipid level control are established factors for identifying people at greatest
      risk of DKD development and progression. Absolute albumin excretion rate (AER)
      and glomerular filtration rate (GFR) measurements also are important, although
      AER categorization generally lacks the necessary specificity and sensitivity, and
      estimates of declining GFR are compromised by methodological limitations for GFRs
      in the normal-to-high range. Emerging risk markers for progressive loss of kidney
      function include markers of oxidation and inflammation, profibrotic cytokines,
      uric acid, advanced glycation end products, functional and structural markers of
      vascular dysfunction, kidney structural changes, and tubular biomarkers. Among
      these, the most promising are serum uric acid and soluble tumor necrosis factor
      receptor (type 1 and type 2) levels, especially in relation to GFR changes. At
      present, these can only be considered as risk markers because they only identify
      an individual at increased risk of progressive DKD and not necessarily related to
      the causal pathway promoting kidney damage. Further work is needed to establish
      whether modulating these factors improves the prognosis in DKD. Although change
      in urinary peptidome levels also is a promising marker, there currently is
      neither a clinical assay nor adequate studies defining its prognostic value.
      Until these or other novel markers become available for clinical use, predictive
      accuracy often may be increased with greater attention to established markers. 

PMID- 24461731
TI  - The use of 15-point hypomanic checklist in differentiating bipolar I and bipolar
      II disorder from major depressive disorder.
AB  - OBJECTIVES: Individuals with bipolar disorder (BP) are often misdiagnosed with
      major depressive disorder (MDD). In this study, we developed a Chinese version of
      15-point hypomania scale (HCL-15) in order to determine its sensitivity and
      specificity in the diagnosis of BP and BP-II in particular. METHODS: A total of
      623 individuals suffering a major depressive episode (MDE) were systematically
      interviewed with both Structured Clinical Interview for DSM-IV-TR Axis I
      Disorders, Patient Edition, and HCL-15. A cutoff score of 8 or more in HCL-15 was
      suggested for BP. RESULTS: Of the 623 depressed patients, 115 (18.5%) actually
      required a diagnosis of BP-I, and another 159 (25.5%) could be more appropriately
      diagnosed with BP-II, according to the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, criteria. The sensitivity of 15-HCL in
      detection of BP-II was 0.78 and 0.46 for BP-I; the specificity was 0.9 and 0.69,
      respectively. The specificity of HCL-15 for BP versus MDD was as high as 0.93.
      Approximately 60%-80% of all questions in the HCL-15 questionnaire revealed
      positive responses from patients, while items 11 and 12, measuring the
      consumption of alcohol, coffee and cigarettes, demonstrated a low positive
      response rate. CONCLUSIONS: The HCL-15 assessment scale was fairly sensitive and
      highly specific for a BP-II diagnosis but not for a BP-I diagnosis. Some items in
      the HCL-15 symptom list need to be further modified to better fit Chinese culture
      and customs. The HCL-15 scale could be a useful tool in clinical practice for
      screening individuals with BP-II in order to avoid a misdiagnosis of MDD.

PMID- 24461732
TI  - [FRAX(r) thresholds to identify people with high or low risk of osteoporotic
      fracture in Spanish female population].
AB  - BACKGROUND AND OBJECTIVE: To detect FRAX((r)) threshold levels that identify
      groups of the population that are at high/low risk of osteoporotic fracture in
      the Spanish female population using a cost-effective assessment. PATIENTS AND
      METHODS: This is a cohort study. Eight hundred and sixteen women 40-90 years old
      selected from the FRIDEX cohort with densitometry and risk factors for fracture
      at baseline who received no treatment for osteoporosis during the 10 year follow
      up period and were stratified into 3 groups/levels of fracture risk (low<10%, 10
      20% intermediate and high>20%) according to the real fracture incidence. RESULTS:
      The thresholds of FRAX((r)) baseline for major osteoporotic fracture were: low
      risk<5; intermediate >= 5 to <7.5 and high >= 7.5. The incidence of fracture with
      these values was: low risk (3.6%; 95% CI 2.2-5.9), intermediate risk (13.7%; 95%
      CI 7.1-24.2) and high risk (21.4%; 95% CI12.9-33.2). The most cost-effective
      option was to refer to dual energy X-ray absorptiometry (DXA-scan) for
      FRAX((r))>= 5 (Intermediate and high risk) to reclassify by FRAX((r)) with DXA
      scan at high/low risk. These thresholds select 17.5% of women for DXA-scan and
      10% for treatment. With these thresholds of FRAX((r)), compared with the strategy
      of opportunistic case finding isolated risk factors, would improve the predictive
      parameters and reduce 82.5% the DXA-scan, 35.4% osteoporosis prescriptions and
      28.7% cost to detect the same number of women who suffer fractures. CONCLUSIONS:
      The use of FRAX (r) thresholds identified as high/low risk of osteoporotic
      fracture in this calibration (FRIDEX model) improve predictive parameters in
      Spanish women and in a more cost-effective than the traditional model based on
      the T-score <= -2.5 of DXA scan.

PMID- 24461733
TI  - What makes a conscious process conscious?
AB  - Newell & Shanks' (N&S's) critical review considers only a very limited sense in
      which mental processes can be thought of as either conscious or unconscious and
      consequently gives a misleading analysis of the role of consciousness in human
      information processing. This commentary provides an expanded analysis of
      conscious processing that also reveals the various ways in which mental processes
      are unconscious. 

PMID- 24461730
TI  - New insights into molecular mechanisms of diabetic kidney disease.
AB  - Diabetic kidney disease remains a major microvascular complication of diabetes
      and the most common cause of chronic kidney failure requiring dialysis in the
      United States. Medical advances over the past century have substantially improved
      the management of diabetes mellitus and thereby have increased patient survival.
      However, current standards of care reduce but do not eliminate the risk of
      diabetic kidney disease, and further studies are warranted to define new
      strategies for reducing the risk of diabetic kidney disease. In this review, we
      highlight some of the novel and established molecular mechanisms that contribute
      to the development of the disease and its outcomes. In particular, we discuss
      recent advances in our understanding of the molecular mechanisms implicated in
      the pathogenesis and progression of diabetic kidney disease, with special
      emphasis on the mitochondrial oxidative stress and microRNA targets.
      Additionally, candidate genes associated with susceptibility to diabetic kidney
      disease and alterations in various cytokines, chemokines, and growth factors are
      addressed briefly. 

PMID- 24461735
TI  - In vivo evidence that phenylalanine 171 acts as a molecular brake for translesion
      DNA synthesis across benzo[a]pyrene DNA adducts by human DNA polymerase kappa.
AB  - Humans possess multiple specialized DNA polymerases that continue DNA replication
      beyond a variety of DNA lesions. DNA polymerase kappa (Pol kappa) bypasses
      benzo[a]pyrene diolepoxide-N(2)-deoxyguanine (BPDE-N(2)-dG) DNA adducts in an
      almost error-free manner. In the previous work, we changed the amino acids close
      to the adducts in the active site and examined the bypass efficiency. The
      substitution of alanine for phenylalanine 171 (F171A) enhanced by 18-fold in
      vitro, the efficiencies of dCMP incorporation opposite (-)- and (+)-trans-anti
      BPDE-N(2)-dG. In the present study, we established human cell lines that express
      wild-type Pol kappa (POLK+/-), F171A (POLK F171A/-) or lack expression of Pol
      kappa (POLK-/-) to examine the in vivo significance. These cell lines were
      generated with Nalm-6, a human pre-B acute lymphoblastic leukemia cell line,
      which has high efficiency for gene targeting. Mutations were analyzed with
      shuttle vectors having (-)- or (+)-trans-anti-BPDE-N(2)-dG in the supF gene. The
      frequencies of mutations were in the order of POLK-/->POLK+/->POLK F171A/- both
      in (-)- and (+)-trans-anti-BPDE-N(2)-dG. These results suggest that F171 may
      function as a molecular brake for bypass across BPDE-N(2)-dG by Pol kappa and
      raise the possibility that the cognate substrates for Pol kappa are not BP
      adducts in DNA but may be lesions in DNA induced by endogenous mutagens. 

PMID- 24461734
TI  - A role for XLF in DNA repair and recombination in human somatic cells.
AB  - Classic non-homologous end-joining (C-NHEJ) is required for the repair of
      radiation-induced DNA double-strand breaks (DSBs) in mammalian cells and plays a
      critical role in lymphoid V(D)J recombination. A core C-NHEJ component is the DNA
      ligase IV co-factor, Cernunnos/XLF (hereafter XLF). In patients, mutations in XLF
      cause predicted increases in radiosensitivity and deficits in immune function,
      but also cause other less well-understood pathologies including neural disorders.
      To characterize XLF function(s) in a defined genetic system, we used a
      recombinant adeno-associated virus-mediated gene targeting strategy to inactivate
      both copies of the XLF locus in the human HCT116 cell line. Analyses of XLF-null
      cells (which were viable) showed that they were highly sensitive to ionizing
      radiation and a radiomimetic DNA damaging agent, etoposide. XLF-null cells had
      profound DNA DSB repair defects as measured by in vivo plasmid end-joining assays
      and were also dramatically impaired in their ability to form either V(D)J coding
      or signal joints on extrachromosomal substrates. Thus, our somatic XLF-null cell
      line recapitulates many of the phenotypes expected from XLF patient cell lines.
      Subsequent structure:function experiments utilizing the expression of wild-type
      and mutant XLF cDNAs demonstrated that all of the phenotypes of an XLF deficiency
      could be rescued by the overexpression of a wild-type XLF cDNA. Unexpectedly,
      mutant forms of XLF bearing point mutations at amino acid positions L115 and
      L179, also completely complemented the null phenotype suggesting, in contrast to
      predictions to the contrary, that these mutations do not abrogate XLF function.
      Finally, we demonstrate that the absence of XLF causes a small, but significant,
      increase in homologous recombination, implicating XLF in DSB pathway choice
      regulation. We conclude that human XLF is a non-essential, but critical, C-NHEJ
      repair factor. 

PMID- 24461737
TI  - [Ten years of emergency attendances for cocaine-users in Spain].
AB  - Cocaine is the second most consumed illegal drug in the western world, following
      cannabis. Since 1998, it is also the drug that more attendances generate in
      different emergency devices, and it is responsible for more of 60% of the
      emergencies directly related to drug consumption. This work reviews the main
      Spanish scientific articles published in the last 10 years, in which different
      factors related to the use of this drug have been analyzed in relation to the use
      of emergency by cocaine users. A total of 8,795 patients were included (interval
      57-1,755), with an average age of 32.64 years (SD 3.02), and an average
      percentage of positives to cocaine of 54.78% (SD 47.03); there were 7 works with
      100% of subjects being positive to cocaine. Males predominated with an average of
      78.69% (SD 12). They presented cardiovascular symptoms in 30% cases (SD 22.7),
      neurological symptoms in 11.6% cases (SD 4.28) and psychiatric symptoms in 49.32%
      cases (SD 23.87). There was a multiple consumption in 49.02% of patients
      (interval 4.3-76.2), fundamentally associated with alcohol (57.78%, SD 6.18) and
      cannabis (21.56%, SD 10.72). Two hundred and forty-six patients (2.8%) needed
      admission and 8 died (0.09%). 

PMID- 24461738
TI  - [New therapies for rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease
      characterized by inflammation of the synovial membrane and progressive
      destruction of the articular cartilage and bone. Advances in the knowledge of
      disease pathogenesis allowed the identification of novel therapeutic targets such
      as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT
      phosphorylation. At present there are 5 TNF antagonists approved for RA.
      Tocilizumab blocks the pathway of IL-6 and is the only biological with proven
      efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept
      provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is
      the first kinase inhibitor approved for this disease. Biologic drugs have proven
      efficacy, almost always in combination with methotrexate, and even halt
      radiographic progression. Monitoring infection is the main precaution in handling
      these patients. 

PMID- 24461739
TI  - [Psychopathologic status in patients with chronic fatigue syndrome, associated or
      not with multiple chemical sensitivity].

PMID- 24461736
TI  - Mass spectrometry-based quantification of the cellular response to methyl
      methanesulfonate treatment in human cells.
AB  - Faithful transmission of genetic material is essential for cell viability and
      organism health. The occurrence of DNA damage, due to either spontaneous events
      or environmental agents, threatens the integrity of the genome. The consequences
      of these insults, if allowed to perpetuate and accumulate over time, are
      mutations that can lead to the development of diseases such as cancer. Alkylation
      is a relevant DNA lesion produced endogenously as well as by exogenous agents
      including certain chemotherapeutics. We sought to better understand the cellular
      response to this form of DNA damage using mass spectrometry-based proteomics. For
      this purpose, we performed sub-cellular fractionation to monitor the effect of
      methyl methanesulfonate (MMS) treatment on protein localization to chromatin. The
      levels of over 500 proteins were increased in the chromatin-enriched nuclear
      lysate including histone chaperones. Levels of ubiquitin and subunits of the
      proteasome were also increased within this fraction, suggesting that ubiquitin
      mediated degradation by the proteasome has an important role in the chromatin
      response to MMS treatment. Finally, the levels of some proteins were decreased
      within the chromatin-enriched lysate including components of the nuclear pore
      complex. Our spatial proteomics data demonstrate that many proteins that
      influence chromatin organization are regulated in response to MMS treatment,
      presumably to open the DNA to allow access by other DNA damage response proteins.
      To gain further insight into the cellular response to MMS-induced DNA damage, we
      also performed phosphorylation enrichment on total cell lysates to identify
      proteins regulated via post-translational modification. Phosphoproteomic analysis
      demonstrated that many nuclear phosphorylation events were decreased in response
      to MMS treatment. This reflected changes in protein kinase and/or phosphatase
      activity in response to DNA damage rather than changes in total protein
      abundance. Using these two mass spectrometry-based approaches, we have identified
      a novel set of MMS-responsive proteins that will expand our understanding of DNA
      damage signaling. 

PMID- 24461740
TI  - [Urinary tract lesions associated to ketamine consumption].

PMID- 24461741
TI  - [Hypophosphatemia, a poorly known adverse reaction of intravenous use of iron].

PMID- 24461743
TI  - MDR tuberculosis challenges global health-care targets.

PMID- 24461742
TI  - Spatial cytokine distribution following traumatic injury.
AB  - Temporal changes in cytokine concentrations following traumatic injuries have
      been extensively studied. Less is known regarding spatial differences in cytokine
      concentrations following traumatic injury. The primary aim of this study was to
      determine the spatial relationship between cytokines and the zone of injury
      (ZOI). Muscle and vessel tissues obtained from rats subjected to an open femoral
      fracture were analyzed to determine if spatial cytokine gradients exist that
      could potentially be used as biomarkers of the ZOI. Samples were collected at 4
      time points following fracture from 3 distinct locations: at the fracture site, 1
      cm away from the fracture, and from the opposite leg. The concentrations of IL-6,
      IL-1alpha, IL-1beta, IL-2, GM-CSF, TNF-alpha, and MIP-1alpha were quantified in
      each sample. Temporally and spatially regulated variations in cytokine
      concentrations were found. IL-6 showed the most promise as a ZOI biomarker with
      statistically different spatial concentrations that were inversely proportional
      to the distance from the fracture in both tissues. IL-1beta and IL-2 also showed
      spatial differences in concentration in both tissues, while GM-CSF, MIP-1alpha,
      and TNF-alpha showed spatial differences in vessel samples. These results
      demonstrate that spatial cytokine gradients exist following traumatic injury,
      representing potential biomarkers that may be used to define the ZOI. 

PMID- 24461744
TI  - The expanding list of zoonotic influenza viruses.

PMID- 24461745
TI  - The club cell and its protein, CC16: time to shine.

PMID- 24461746
TI  - Molecular methods for tuberculosis trials: time for whole-genome sequencing?

PMID- 24461747
TI  - The first volume and beyond.

PMID- 24461749
TI  - Highlights of the 44th union world conference on lung health.

PMID- 24461750
TI  - An international focus for lung imaging and cancer screening.

PMID- 24461751
TI  - Pneumonia has its day.

PMID- 24461752
TI  - Spare inhalers in schools could prevent child asthma deaths.

PMID- 24461753
TI  - Telemonitoring for COPD does not reduce hospital admissions.

PMID- 24461754
TI  - Homelessness and respiratory disease.

PMID- 24461755
TI  - Do art lovers make better doctors?

PMID- 24461756
TI  - Human infection with avian influenza A H6N1 virus: an epidemiological analysis.
AB  - BACKGROUND: Avian influenza A H6N1 virus is one of the most common viruses
      isolated from wild and domestic avian species, but human infection with this
      virus has not been previously reported. We report the clinical presentation,
      contact, and environmental investigations of a patient infected with this virus,
      and assess the origin and genetic characteristics of the isolated virus. METHODS:
      A 20-year-old woman with an influenza-like illness presented to a hospital with
      shortness of breath in May, 2013. An unsubtyped influenza A virus was isolated
      from her throat-swab specimen and was transferred to the Taiwan Centres for
      Disease Control (CDC) for identification. The medical records were reviewed to
      assess the clinical presentation. We did a contact and environmental
      investigation and collected clinical specimens from the case and symptomatic
      contacts to test for influenza virus. The genomic sequences of the isolated virus
      were determined and characterised. FINDINGS: The unsubtyped influenza A virus was
      identified as the H6N1 subtype, based on sequences of the genes encoding
      haemagglutinin and neuraminidase. The source of infection was not established.
      Sequence analyses showed that this human isolate was highly homologous to chicken
      H6N1 viruses in Taiwan and had been generated through interclade reassortment.
      Notably, the virus had a G228S substitution in the haemagglutinin protein that
      might increase its affinity for the human alpha2-6 linked sialic acid receptor.
      INTERPRETATION: This is the first report of human infection with a wild avian
      influenza A H6N1 virus. A unique clade of H6N1 viruses with a G228S substitution
      of haemagglutinin have circulated persistently in poultry in Taiwan. These
      viruses continue to evolve and accumulate changes, increasing the potential risk
      of human-to-human transmission. Our report highlights the continuous need for
      preparedness for a pandemic of unpredictable and complex avian influenza.
      FUNDING: Taiwan Centres for Disease Control.

PMID- 24461757
TI  - Serum concentrations of club cell secretory protein (Clara) and cancer mortality
      in adults: a population-based, prospective cohort study.
AB  - BACKGROUND: Club cell secretory protein (Clara) (CC16) is produced mainly by
      bronchiolar club cells and has been shown to have protective effects against
      airway inflammation and oxidative stress from cigarette smoking and related
      carcinogens. The goal of this study was to establish whether serum CC16
      concentrations predict all-cause and cancer-specific mortality in adults.
      METHODS: We used data from the population-based Tucson Epidemiological Study of
      Airway Obstructive Diseases (TESAOD), a prospective cohort study of respiratory
      health initiated in Tucson, AZ, USA, in 1972, that recruited a multistage
      stratified cluster sample of non-Hispanic white households. We measured serum
      CC16 concentrations in cryopreserved serum samples and reviewed vital status up
      to Jan 1, 2011, through contact with next of kin, collection of death
      certificates, and searches of the National Death Index. Our primary analysis was
      the relation of baseline serum CC16 to all-cause mortality or cause-specific
      mortality risk, analysed by adjusted Cox proportional hazards models. FINDINGS:
      1086 TESAOD participants aged 21-70 years at enrolment were eligible for
      inclusion. Of these, 653 (60%) had died by 2011, and cause of death was
      ascertained for 649 (99%). When adjusted for sex, age, education, body-mass
      index, smoking and pack-years, and baseline levels of lung function, serum CC16
      concentrations at baseline were inversely associated with mortality risk over the
      study follow-up. Mortality risk increased for each 1-SD decrease in CC16
      (adjusted hazard ratio [HR] 1.16 [95% CI 1.06-1.26]; p=0.0007). For cause
      specific mortality, each 1-SD decrease in serum CC16 was associated with an
      increased risk of dying of cancer (adjusted HR 1.41 [1.19-1.67]; p<0.0001). In
      the subset of smokers, the corresponding adjusted HR for mortality by lung cancer
      was 1.52 (1.14-2.03; p=0.004). INTERPRETATION: Serum CC16 concentrations can
      predict mortality risk in the general adult population. The excess risk
      associated with lower CC16 concentrations is predominantly driven by cancer,
      particularly lung cancer. FUNDING: National Heart, Lung, and Blood Institute.

PMID- 24461759
TI  - Future clinical applications of genomics for acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome remains a substantial cause of morbidity and
      mortality in intensive care units, yet no specific pharmacotherapy has proven
      useful in reducing the duration of mechanical ventilation or improving survival.
      One factor that might hamper the development of treatment for acute respiratory
      distress syndrome is the heterogeneous nature of the population who present with
      the syndrome. In this Review, the potential of genomic approaches-genetic
      association, gene expression, metabolomic, proteomic, and systems biology
      applications-for the identification of molecular endotypes within acute
      respiratory distress syndrome and potentially for the prediction, diagnosis,
      prognosis, and treatment of this difficult disorder are discussed. 

PMID- 24461758
TI  - Whole-genome sequencing to establish relapse or re-infection with Mycobacterium
      tuberculosis: a retrospective observational study.
AB  - BACKGROUND: Recurrence of tuberculosis after treatment makes management difficult
      and is a key factor for determining treatment efficacy. Two processes can cause
      recurrence: relapse of the primary infection or re-infection with an exogenous
      strain. Although re-infection can and does occur, its importance to tuberculosis
      epidemiology and its biological basis is still debated. We used whole-genome
      sequencing-which is more accurate than conventional typing used to date-to assess
      the frequency of recurrence and to gain insight into the biological basis of re
      infection. METHODS: We assessed patients from the REMoxTB trial-a randomised
      controlled trial of tuberculosis treatment that enrolled previously untreated
      participants with Mycobacterium tuberculosis infection from Malaysia, South
      Africa, and Thailand. We did whole-genome sequencing and mycobacterial
      interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing
      of pairs of isolates taken by sputum sampling: one from before treatment and
      another from either the end of failed treatment at 17 weeks or later or from a
      recurrent infection. We compared the number and location of SNPs between isolates
      collected at baseline and recurrence. FINDINGS: We assessed 47 pairs of isolates.
      Whole-genome sequencing identified 33 cases with little genetic distance (0-6
      SNPs) between strains, deemed relapses, and three cases for which the genetic
      distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of
      relapse and six cases of mixed infection were classified differently by whole
      genome sequencing and MIRU-VNTR. We detected five single positive isolates
      (positive culture followed by at least two negative cultures) without clinical
      evidence of disease. INTERPRETATION: Whole-genome sequencing enables the
      differentiation of relapse and re-infection cases with greater resolution than do
      genotyping methods used at present, such as MIRU-VNTR, and provides insights into
      the biology of recurrence. The additional clarity provided by whole-genome
      sequencing might have a role in defining endpoints for clinical trials. FUNDING:
      Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB
      Drug Development, European and Developing Country Clinical Trials Partnership.

PMID- 24461760
TI  - Vitamin D and chronic obstructive pulmonary disease: hype or reality?
AB  - Abundant laboratory findings show the important role vitamin D has in the innate
      and adaptive immune system. In human beings, observational studies have
      associated vitamin D deficiency with an increased risk for different
      inflammatory, infectious, and autoimmune diseases. With regard to chronic
      obstructive pulmonary disease (COPD), conflicting data have been reported. Most
      epidemiological studies have been restricted by their design, and larger
      longitudinal studies of population-based samples and of cohorts with COPD are
      warranted. An alternative explanation for the discordant results in COPD might be
      related to the complexity of the intracellular vitamin D signalling pathway,
      which is not shown in systemic levels of the precursor 25-hydroxyvitamin D. For
      COPD in particular, we speculate that local downregulation of vitamin D
      signalling from and beyond the receptor might clarify why pro-inflammatory
      processes in the airways are not or are insufficiently countered by vitamin D
      dependent control mechanisms. In a disease already characterised by
      glucocorticoid resistance, the potential activation and reactivation of an
      intrinsic comprehensive system of immune control should attract more attention to
      design appropriate interventions with promising therapeutic potential. 

PMID- 24461762
TI  - Integrating real-life studies in the global therapeutic research framework.

PMID- 24461763
TI  - COPD patients trapped in the financial crisis in rural Crete.

PMID- 24461761
TI  - Diet and asthma: vitamins and methyl donors.
AB  - Diet changes can partly explain the high burden of asthma in industrialised
      nations. Findings from experimental studies have stimulated many observational
      studies of the association between vitamins (A, C, D, and E) or nutrients acting
      as methyl donors (folate, vitamin B12, and choline) and asthma. However,
      observational studies are susceptible to several sources of bias; well conducted
      randomised controlled trials (RCTs) are the gold standard to establish whether
      diet has an effect on asthma. Evidence from observational studies and a few RCTs
      strongly justifies ongoing and future RCTs in three areas: vitamin D for the
      prevention or treatment of asthma, choline supplementation as adjuvant treatment
      for asthma, and vitamin E to prevent the detrimental effects of air pollution in
      patients with asthma. At present, insufficient evidence exists to recommend
      supplementation with any vitamin or nutrient acting as a methyl donor to prevent
      or treat asthma. 

PMID- 24461765
TI  - Incidence of congenital cytomegalovirus infection in Ireland: implications for
      screening and diagnosis.
AB  - BACKGROUND: Congenital cytomegalovirus (cCMV) causes serious intrauterine
      infection and is the leading cause of sensorineural hearing loss. In the absence
      of routine screening, asymptomatic infections, which constitute approximately 90%
      of all cCMV cases, remain undiagnosed; however many clinical abnormalities
      manifest later in childhood. OBJECTIVES: The aims of the present study were to
      determine, for the first time, the incidence of cCMV infection in a large
      maternity hospital in Dublin city and the optimal sampling method for neonatal
      screening. STUDY DESIGN: A pilot screening study of asymptomatic infants born was
      conducted over a 12-month period. Mothers were consented and neonates screened
      for evidence of CMV infection (n=1044). Urine or saliva was tested for the
      presence of CMV DNA and reactive results were confirmed with follow-up testing
      and clinical evaluation. RESULTS: cCMV incidence in the asymptomatic neonates
      screened was 0.19%. An overall cCMV incidence was extrapolated based on the total
      number of live-births and data from those infants routinely screened for cCMV
      during the study period, and estimated as 0.23%. Neonatal urine collection proved
      prohibitive to mass screening. However, testing of saliva for CMV DNA was rapid,
      sensitive and suitable for screening. Furthermore, in a low prevalence
      population, pooling of patient samples proved effective and cost-efficient.
      CONCLUSIONS: The present study concluded that there is a significant burden of
      undiagnosed cCMV infection in Ireland. The introduction of neonatal CMV DNA
      testing of saliva is viable, and could be considered as part of the national
      newborn screening programme, following a cost-benefit analysis.

PMID- 24461764
TI  - Does HIV-1 co-receptor tropism correlate with fibrosis progression in HIV/HCV co
      infected patients?
AB  - BACKGROUND: In HIV/HCV co-infected patients, HIV-1 gp120 activates human hepatic
      stellate cells (HSCs) which play a key role in fibrosis pathogenesis. It is still
      unclear whether pro-fibrogenic effects are more attributable to X4 or R5 strains
      in vivo. OBJECTIVE: To assess if HIV-1 X4 or R5 variants are associated with a
      different progression of fibrosis. STUDY DESIGN: A total of 105 HIV/HCV co
      infected patients were submitted to gp120 sequencing on proviral DNA and
      classified as X4 or R5 based on g2p (20% false positive rate). The fibrosis
      evolution was retrospectively determined by means of APRI and FIB-4 scores at 3
      month intervals from the first anti-HCV-positive test. The association of co
      receptor tropism with increased fibrosis scores was evaluated by linear mixed
      models. RESULTS: X4 variants were found in 41 patients (39%). The median
      observation period was similar in X4 and R5 patients (17 years). No difference
      was observed between the two groups of patients, except for nadir CD4 which was
      lower in X4 compared to R5 (percentage, p=0.005, and absolute number, p=0.005).
      X4 and R5 patients did not significantly differ for FIB-4 and APRI score over
      time (p=0.5, and p=0.1, respectively). No association between HCV-RNA levels over
      time and co-receptor tropism was noted (p=0.9). Conversely, a significant
      correlation of fibrosis scores with gamma-glutamyl transferase levels, lower
      current CD4 count, HIV viremia and use of antiretrovirals was observed.
      CONCLUSIONS: This retrospective analysis of fibrosis evolution did not support
      the evidence of a differing pro-fibrogenic activity for X4 and R5 HIV-1 variants
      in HIV/HCV co-infected patients.

PMID- 24461766
TI  - Quantification of myocardial iron deficiency in nonischemic heart failure by
      cardiac T2* magnetic resonance imaging.
AB  - The aim of this study was to use T2* cardiac magnetic resonance (CMR) imaging to
      quantify myocardial iron content in patients with heart failure (HF) and to
      investigate the relation between iron content, cardiac function, and the cause of
      HF. CMR data were analyzed from 167 patients with nonischemic and 31 with
      ischemic HF and 50 patients with normal ventricular function. Short-axis T2*
      imaging was accomplished using 3-T scanner and multiecho gradient-echo sequence.
      Myocardial T2* value (M-T2*) was calculated by fitting the signal intensity data
      for the mid-left ventricular (LV) septum to a decay curve. Patients with
      nonischemic HF were categorized into patients with LV ejection fraction (LVEF)
      <35% or >=35%. The relation between nonischemic HF with LVEF <35% and the risk
      for major adverse cardiac events was analyzed by multivariate logistic regression
      analysis using M-T2* and HF biomarkers. M-T2* was significantly greater for
      patients with nonischemic HF (LVEF <35%: 29 +/- 7 ms, LVEF >=35%: 26 +/- 5 ms)
      than for patients with normal LV function (22 +/- 3 ms, p <0.0001) or ischemic HF
      (22 +/- 4 ms, p <0.001). The odds ratio was 1.21 for M-T2* (p <0.0001) and 1.0015
      for brain natriuretic peptide (p <0.0001) in relation to nonischemic HF with LVEF
      <35%. Furthermore, this value was 0.96 for systolic blood pressure (p = 0.012)
      and 1.02 for M-T2* (p = 0.03) in relation to the risk for major adverse cardiac
      events in patients with nonischemic HF. In conclusion, T2* CMR demonstrated the
      robust relation between myocardial iron deficiency and nonischemic HF. M-T2* is a
      biomarker that can predict adverse cardiac function in patients with nonischemic
      HF.

PMID- 24461767
TI  - Heart rate recovery in patients with hypertrophic cardiomyopathy.
AB  - Recovery in heart rate (HR) after exercise is a measure of autonomic function and
      a prognostic indicator in cardiovascular disease. The aim of this study was to
      characterize heart rate recovery (HRR) and to determine its relation to cardiac
      function and morphology in patients with hypertrophic cardiomyopathy (HC). We
      studied 18 healthy volunteers and 41 individuals with HC. All patients underwent
      clinical assessment and transthoracic echocardiography. Continuous beat-by-beat
      assessment of HR was obtained during and after cardiopulmonary exercise testing
      using finger plethysmography. HRR and power spectral densities were calculated on
      3 minutes of continuous RR recordings. Absolute HRR was lower in patients than
      that in controls at 1, 2, and 3 minutes (25.7 +/- 8.4 vs 35.3 +/- 11.0 beats/min,
      p <0.001; 36.8 +/- 9.4 vs 53.6 +/- 13.2 beats/min, p <0.001; 41.2 +/- 12.2 vs
      62.1 +/- 14.5 beats/min, p <0.001, respectively). HRR remained lower in patients
      at 2 and 3 minutes after normalization to peak HR. After normalization to the
      difference in HR between peak exercise and rest, HRR was significantly impaired
      in individuals with obstructive HC at 3 minutes compared with controls. HR at 3
      minutes correlated with peak left ventricular outflow tract gradient (B 0.154
      beats/min/mm Hg, confidence interval 0.010 to 0.299, p = 0.037) and remained a
      significant predictor of HRR after multivariable analysis. Spectral analysis
      showed a trend toward an increased low-frequency to high-frequency ratio in
      patients (p = 0.08) suggesting sympathetic predominance. In conclusion, HRR is
      impaired in HC and correlates with the severity of left ventricular outflow tract
      gradient. Prospective studies of the prognostic implications of impaired HRR in
      HC are warranted.

PMID- 24461768
TI  - Risk factors for progression of functional tricuspid regurgitation.
AB  - The aim of this study was to determine the risk factors for tricuspid
      regurgitation (TR) progression in a contemporary population of patients referred
      for echocardiography. In a case-control study, we compared 100 consecutive
      patients with TR progression on serial echocardiograms (trivial or mild TR on the
      first echocardiogram and moderate or severe functional TR on a follow-up
      echocardiogram) with 100 patients matched for age and gender, having mild TR at
      baseline and no TR progression. Mean age was 72 +/- 10 years, 55% were males, and
      time to TR progression was 5.3 +/- 2.9 years. Less than 10% had rheumatic heart
      disease. Left ventricular ejection fraction was preserved (>=50%) in 85% of the
      TR progression group and in 74% of the control group (p = 0.06). Pulmonary artery
      systolic pressure increased from 41 +/- 16 to 56 +/- 18 mm Hg in the TR
      progression group and decreased from 44 +/- 13 to 41 +/- 11 mm Hg in the control
      group (p <0.0001). Independent risk factors for TR progression were pulmonary
      artery systolic pressure change during follow-up (odds ratio per 1 mm Hg 1.14,
      95% confidence interval 1.06 to 1.23, p <0.0001), permanent atrial fibrillation
      (odds ratio 14.3, 95% confidence interval 4.6 to 44.2, p <0.0001), and coronary
      artery disease (odds ratio 5.7, 95% confidence interval 1.4 to 22.8, p = 0.015).
      All-cause mortality at 3 years was 20% for patients without TR progression, 42%
      for moderate TR, and 63% for severe TR, p <0.0001. Progression-to-severe TR
      independently predicted subsequent mortality. In conclusion, in patients with low
      prevalence of rheumatic heart disease and preserved left ventricular ejection
      fraction, pulmonary artery systolic pressure increase and permanent atrial
      fibrillation were the most powerful risk factors for TR progression. Progression
      to-severe TR was an independent predictor of subsequent mortality.

PMID- 24461769
TI  - Meta-analysis of effects of optimization of cardiac resynchronization therapy on
      left ventricular function, exercise capacity, and quality of life in patients
      with heart failure.
AB  - The contribution of postimplant optimization of device settings to the beneficial
      effect of cardiac resynchronization therapy (CRT) in heart failure is uncertain.
      We performed a meta-analysis to investigate the impact of CRT optimization on the
      improvement of left ventricular function, exercise capacity, and quality of life.
      We undertook a systemic review of the evidence from a search of relevant
      controlled clinical studies in the MEDLINE and EMBASE databases. Changes in left
      ventricular ejection fraction (LVEF), 6-minute walk distance, and Minnesota
      Living with Heart Failure score at follow-up were assessed; the primary outcome
      was ejection fraction. A random-effects model was used to combine weighted mean
      difference (WMD) and 95% confidence intervals (CIs). A metaregression was
      undertaken to assess the impact of potential covariates. Data were collated from
      13 studies enrolling 1,431 patients (919 optimized and 669 controls). Pooled
      analysis demonstrated that the optimization procedure resulted in a significant
      increase in LVEF (WMD 2.6%, 95% CI 0.8 to 4.4, p = 0.001) as compared with a
      nonoptimized CRT. No improvements with the optimization of CRT were seen in 6
      minute walk distance and quality of life (WMD 12 m, 95% CI 23 to 48, p = 0.49,
      and 3.6, 95% CI 2.2 to 9.5, p = 0.22, respectively); however, this part of the
      analysis was performed using limited data. Thus, these collated data suggest that
      the optimization of CRT leads to a significant but small improvement in LVEF in
      patients with heart failure. Additional, adequately powered studies are needed to
      evaluate the effects of this procedure on exercise tolerance and quality of life.

PMID- 24461770
TI  - Long-term prognostic value of mitral regurgitation in patients with ST-segment
      elevation myocardial infarction treated by primary percutaneous coronary
      intervention.
AB  - The presence of mitral regurgitation (MR) is associated with an impaired
      prognosis in patients with ischemic heart disease. However, data with regard to
      the impact of this condition in patients with ST-segment elevation myocardial
      infarction (STEMI) treated by means of primary percutaneous coronary intervention
      (PPCI) are lacking. Our aim was to assess the effect of MR in the long-term
      prognosis of patients with STEMI after PPCI. We analyzed a prospective registry
      of 1,868 patients (mean age 62 +/- 13 years, 79.9% men) with STEMI treated by
      PPCI in our center from January 2006 to December 2010. Our primary outcome was
      the composite end point of all-cause mortality or admission due to heart failure
      during follow-up. After exclusions, 1,036 patients remained for the final
      analysis. Moderate or severe MR was detected in 119 patients (11.5%). Those with
      more severe MR were more frequently women (p <0.001), older (p <0.001), and with
      lower ejection fraction (p <0.001). After a median follow-up of 2.8 years (1.7 to
      4.3), a total of 139 patients (13.4%) experienced our primary end point. There
      was an association between the unfavorable combined event and the degree of MR (p
      <0.001). After adjustment for relevant confounders, moderate or severe MR
      remained as an independent predictor of the combined primary end point (adjusted
      hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.57 to 6.27) and each event
      separately (adjusted HR death 3.1, 95% CI 1.34 to 7.2; adjusted HR heart failure
      3.3, 95% CI 1.16 to 9.4). In conclusion, moderate or severe MR detected early
      with echocardiography was independently associated with a worse long-term
      prognosis in patients with STEMI treated with PPCI. 

PMID- 24461772
TI  - Intestinal transplantation: An overview.
AB  - Intestinal transplantation may become necessary in patients with short bowel
      syndrome (SBS) who fail intestinal rehabilitation. Most children requiring
      intestinal transplantation (68%) have SBS due to anatomic loss. Intestinal
      transplantation can occur in isolation or in combination with other organs. Many
      children will have advanced liver disease at the time of referral and will
      undergo combined liver-small bowel transplantation. Considerable progress in
      immunosuppression has led to decreased rates of acute rejection after
      transplantation and to improved early allograft survival while minimizing
      toxicity.Survival with small bowel transplantations has greatly improved over the
      last 20 years with chronic rejection being the major contributing cause to late
      graft loss. 

PMID- 24461771
TI  - Impact of gender on the prognosis of patients with nonvalvular atrial
      fibrillation.
AB  - Treatment guidelines for atrial fibrillation (AF) used in Western countries
      describe female gender as a risk factor for thromboembolic events in patients
      with nonvalvular AF (NVAF). The present study aimed to determine the impact of
      gender on prognosis of Japanese patients with NVAF. A subanalysis of 7,406
      patients with NVAF (mean age 70 years) who were followed-up prospectively for 2
      years was performed using data from the J-RHYTHM registry. The primary end points
      were thromboembolic events, major hemorrhaging, total mortality, and
      cardiovascular mortality. Compared with male subjects (n = 5,241), female
      subjects (n = 2,165) were older and displayed greater prevalences of paroxysmal
      AF, heart failure, and hypertension but less prevalences of diabetes, previous
      cerebral infarction, and coronary artery disease. Male and female patients had
      mean CHADS2 (Congestive heart failure, Hypertension, Age of 75 years or more,
      Diabetes mellitus and prior Stroke or transient ischemic attack) scores of 1.6
      and 1.8, respectively (p <0.001). Warfarin was given to 87% of male patients and
      86% of female patients (p = 0.760), and the 2 genders displayed similar mean
      international normalized ratio of prothrombin time values at baseline (1.91 vs
      1.90, respectively, p = 0.756). Multivariate logistic regression analysis
      indicated that male gender was an independent risk factor for major hemorrhaging
      (odds ratio 1.59, 95% confidence interval 1.05 to 2.40, p = 0.027) and all-cause
      mortality (odds ratio 1.78, 95% confidence interval 1.25 to 2.55, p <0.002) but
      not for thromboembolic events (odds ratio 1.24, 95% confidence interval 0.83 to
      1.86, p = 0.297) or cardiovascular mortality (odds ratio 0.96, 95% confidence
      interval 0.56 to 1.66, p = 0.893). In conclusion, female gender is not a risk
      factor for thromboembolic events among Japanese patients with NVAF who were
      treated mostly with warfarin. However, male gender is a risk factor for major
      hemorrhaging and all-cause mortality.

PMID- 24461773
TI  - Seroprevalence of parasitic zoonoses and their relationship with social factors
      among the Canadian Inuit in Arctic regions.
AB  - Residents of Arctic communities are at increased risk of contracting infectious
      diseases transmitted by wildlife. Data collected from the International Polar
      Year Inuit Health Survey were used to determine the seroprevalence of 4 parasitic
      zoonoses in three Inuit jurisdictions of the Canadian Arctic and to assess risk
      factors of infection. To date, this is the most comprehensive survey of its kind.
      Immunoenzymatic methods were used for the detection of antibodies against
      Toxocara canis, Echinococcus granulosus, Trichinella sp., and Toxoplasma gondii.
      We determined the weighted prevalence of parasitic infections in 36 Inuit
      communities across the Inuvialuit settlement region, Nunavut, and Nunatsiavut.
      Our results indicate infrequent exposure to Toxocara and Echinococcus (1.7 and
      6.3%, respectively). Exposure to T. gondii (27.2%) and Trichinella (18.6%) was
      more prevalent and was generally higher in Nunavut compared to other northern
      regions. Overall, seropositivity was related to age, education, and consumption
      of marine mammals and seafood. 

PMID- 24461774
TI  - Ancestral differences in femoral neck axis length: possible implications for
      forensic anthropological analyses.
AB  - In forensic anthropological contexts, very few methods of estimating ancestry
      from the postcranial skeleton are available. The cranium is widely recognized to
      show the greatest ancestral variation, and is often regarded by forensic
      anthropologists as the only reliable bone for estimating ancestry from
      unidentified skeletal remains. Several studies have demonstrated ancestral
      variation in aspects of the femur, but none have shown significant predictive
      power for discriminating multiple groups, and have therefore not gained wide
      acceptance by forensic anthropologists. Skeletal health experts (particularly
      bone densitometrists), however, have long recognized a relationship between
      proximal femur geometry (especially hip axis length) and osteoporosis-related
      fracture risk. Moreover, fracture risk has been noted to vary between ancestral
      groups. Here, we investigate whether measurements that are related to fracture
      risk might also be used to estimate ancestry from unidentified skeletal remains.
      Specifically, we investigate ancestral differences in femoral neck axis length
      (FNAL) and find significant differences between European, Asian and African
      groups in both women and men. FNAL was largest in European groups followed by
      African and then Asian groups. The greatest discriminating power was found
      between European and Asian groups, but was also significant between European and
      African groups. These differences may have utility in estimating ancestry in
      forensic anthropological contexts. 

PMID- 24461775
TI  - Sudden death due to dissection of the thoracic aorta associated with dissection
      and rupture of the pulmonary artery: report of two cases.
AB  - We present two cases of dissection of the thoracic aorta associated with
      dissection and rupture of the pulmonary artery. In both cases the initial
      dissection was hypothesized to occur in the thoracic aorta, with secondary
      dissection and rupture of the pulmonary artery. 

PMID- 24461777
TI  - [Abdominal pain of unusual cause].

PMID- 24461776
TI  - No significant association between brain-derived neurotrophic factor gene rs6265
      and cognitive function in Japanese patients with schizophrenia.

PMID- 24461778
TI  - Synthesis and antiviral effects of isosteviol-derived analogues against the
      hepatitis B virus.
AB  - Among several isosteviol-derived analogues, NC-8 (ent-16-oxobeyeran-19-N
      methylureido) showed inhibitory potency against the hepatitis B virus (HBV) in
      HepG2 2.2.15 cells. Its anti-HBV mechanism was then next investigated in a human
      hepatoma cell culture system. Results showed that it specifically inhibited viral
      gene expression and reduced the level of encapsidated viral DNA intermediates in
      Huh7 cells that expressed replicating HBV. It also potently attenuated all viral
      promoter activity in HBV-expressing Huh7 cells, but not in cells lacking HBV
      expression. By examining its antiviral mechanism in cellular signaling pathways,
      NC-8 was found to inhibit the activity of the nuclear factor (NF)-kappaB element
      containing promoter, but only slightly enhanced activities of activator protein
      (AP)-1- and interferon-sensitive response element (ISRE)-containing promoters in
      HBV-expressing cells. NC-8 also significantly eliminated NF-kappaB (p65/p50) and
      Toll-like receptor (TLR)2 proteins, but increased the IkappaBalpha protein level
      in a dose-dependent manner in HBV-transfected Huh7 cells, while these protein
      levels were apparently unchanged in non-transfected cells. Meanwhile, NC-8
      treated nuclear extracts that co-expressed HBV inhibited the binding of NF-kappaB
      to the CS1 site of HBV major surface gene and specifically attenuated CS1
      containing promoter activity. Taken together, this study suggests that the
      antiviral mechanism of NC-8 appears to be mediated by disturbing replication and
      gene expression of HBV and by inhibiting the host TLR2/NF-kappaB signaling
      pathway. 

PMID- 24461780
TI  - Evolution of alkaloid biosynthesis in the genus Narcissus.
AB  - In an attempt to reveal the relationships between alkaloid biosynthesis and
      phylogeny, we investigated by GC-MS the alkaloid patterns of 22 species and 3
      hybrids (from 45 locations) from seven main sections of the genus Narcissus
      (Amaryllidaceae). The results indicate that the first alkaloids to evolve in the
      genus Narcissus were of the lycorine- and homolycorine-type. The alkaloid pattern
      of the Nevadensis section supports its recent separation from the Pseudonarcissus
      section. The plants of Narcissus pallidulus (Ganymedes section) show a
      predominance of Sceletium-type compounds, which are quite rare in the
      Amaryllidaceae family. Two successful evolutionary strategies involving alkaloid
      biosynthesis and leading to an expansion in taxa and occupied area were
      determined. Firstly, a diversification of alkaloid patterns and a high alkaloid
      concentration in the organs of the large Narcissus species (in the
      Pseudonarcissus section) resulted in an improved chemical defence in diverse
      habitats. Secondly, both plant size and alkaloid biosynthesis were reduced (in
      the Bulbocodium and Apodanthi sections) relegated to dry pastures and rocky
      places. 

PMID- 24461779
TI  - High level protein-purification allows the unambiguous polypeptide determination
      of latent isoform PPO4 of mushroom tyrosinase.
AB  - Tyrosinases catalyze two initial reaction steps in the formation of melanin.
      Purification of tyrosinases had always been a process accompanied with various
      problems caused by enzymatic browning processes. Here, an approach is presented
      for the purification of the latent enzyme from mushrooms which averts and removes
      interfering compounds (e.g. polyphenols) in advance to the extraction process.
      The described method is supposed being well suitable as a general protein
      purification protocol from natural sources like fungi and plants. The purified
      enzyme was investigated in detail by means of mass spectrometry: its intact
      protein mass was determined as 64,247.3 Da and it was identified as number four
      of in total six isoforms (PPO1-6) by means of sequence analysis. Some PTMs,
      strain specific sequence disparities and several cleavage sites including the one
      causing enzyme-activation (Ser383) were determined, thus, providing insights on
      the maturation process of this latent tyrosinase zymogen. Based on these sequence
      data it can be concluded that the polypeptide backbone of the latent form of the
      tyrosinase PPO4 ranges from Ser2 to Thr565, missing when compared to the gene
      derived sequence a small part (46 amino acids) of the C-terminal tail. The high
      content on hydrophobic amino acids within this missing tail gives rise to
      speculations whether this part might have a function as a membrane anchor.

PMID- 24461781
TI  - Phytochemical analysis of Rosa hybrida cv. 'Jardin de Granville' by HPTLC, HPLC
      DAD and HPLC-ESI-HRMS: polyphenolic fingerprints of six plant organs.
AB  - The Rosa hybrida cultivar 'Jardin de Granville', a delicate clear pink flower, is
      here investigated through a progressive analytical strategy using complementary
      phytochemical screening methods in order to characterize the polyphenol content
      of several parts of the plant. The microwave hydro-ethanolic extract analysis of
      six different parts of the plant, carried out by High Performance Thin Layer
      Chromatography (HPTLC) and High Performance Liquid Chromatography coupled with a
      Diode Array Detector (HPLC-DAD) enabled initial identification of the polar
      molecular families present in each organ, namely tannins and flavonoids
      (quercetin and kaempferol derivatives). The HPLC fingerprints displayed different
      profiles for each organ, attesting to the original composition and potential
      valuation of the different plant parts. More detailed analyses of the extracts
      were then carried out by High Performance Liquid Chromatography coupled with
      electrospray ionization (ESI) mass spectrometry with a Q-TOF analyzer (ESI-HR-Q
      TOF). Around 60 compounds were identified, mainly gallo-tannins, ellagi-tannins,
      catechin derivatives and glycoside derivatives of quercetin and kaempferol. Some
      compounds such as hyperoside or ellagic acid appeared to be ubiquitous and were
      found in abundance in each plant part. Woods were the richest organ in catechin
      and proanthocyanidin derivatives while kaempferol derivatives were more numerous
      and abundant in bud and flower parts. 

PMID- 24461782
TI  - Evidence of microplastics in samples of zooplankton from Portuguese coastal
      waters.
AB  - Records of high concentrations of plastic and microplastic marine debris floating
      in the ocean have led to investigate the presence of microplastics in samples of
      zooplankton from Portuguese coastal waters. Zooplankton samples collected at four
      offshore sites, in surveys conducted between 2002 and 2008, with three different
      sampling methods, were used in this preliminary study. A total of 152 samples
      were processed and microplastics were identified in 93 of them, corresponding to
      61% of the total. Costa Vicentina, followed by Lisboa, were the regions with
      higher microplastic concentrations (0.036 and 0.033 no. m-3) and abundances (0.07
      and 0.06 cm3 m-3), respectively. Microplastic: zooplankton ratios were also
      higher in these two regions, which is probably related to the proximity of
      densely populated areas and inputs from the Tejo and Sado river estuaries.
      Microplastics polymers were identified using Micro Fourier Transformed Infrared
      Spectroscopy (MU-FTIR), as polyethylene (PE), polypropylene (PP) and
      polyacrylates (PA). The present work is the first report on the composition of
      microplastic particles collected with plankton nets in Portuguese coastal waters.
      Plankton surveys from regular monitoring campaigns conducted worldwide may be
      used to monitor plastic particles in the oceans and constitute an important and
      low cost tool to address marine litter within the scope of the Marine Strategy
      Framework Directive (2008/56/EC).

PMID- 24461783
TI  - [Ataxia and nystagmus of unusual origin].

PMID- 24461784
TI  - Reply: To PMID 24094763.

PMID- 24461785
TI  - Dexamethasone and the brain at age 18 years: randomize the first baby--and follow
      up.

PMID- 24461787
TI  - There's more under the nonalcoholic fatty liver disease umbrella than an elevated
      alanine aminotransferase level.

PMID- 24461786
TI  - Trends in caffeine use and association between clinical outcomes and timing of
      therapy in very low birth weight infants.
AB  - OBJECTIVE: To examine the effect of early initiation of caffeine therapy on
      neonatal outcomes and characterize the use of caffeine therapy in very low birth
      weight (VLBW) infants. STUDY DESIGN: We analyzed a cohort of 62 056 VLBW infants
      discharged between 1997 and 2010 who received caffeine therapy. We compared
      outcomes in infants receiving early caffeine therapy (initial dose before 3 days
      of life) and those receiving late caffeine therapy (initial dose at or after 3
      days of life) through propensity scoring using baseline and early clinical
      variables. The primary outcome was the association between the timing of caffeine
      initiation and the incidence of bronchopulmonary dysplasia (BPD) or death.
      RESULTS: We propensity score-matched 29 070 VLBW infants at a 1:1. Of infants
      receiving early caffeine therapy, 3681 (27.6%) died or developed BPD, compared
      with 4591 infants (34.0%) receiving late caffeine therapy (OR, 0.74; 99% CI, 0.69
      0.80). Infants receiving early caffeine had a lower incidence of BPD (23.1% vs
      30.7%; OR, 0.68; 95% CI, 0.63-0.73) and a higher incidence of death (4.5% vs
      3.7%; OR, 1.23; 95% CI, 1.05-1.43). Infants receiving early caffeine therapy had
      less treatment of patent ductus arteriosus (OR, 0.60; 95% CI, 0.55-0.65) and a
      shorter duration of mechanical ventilation (mean difference, 6 days; P < .001).
      CONCLUSION: Early caffeine initiation is associated with a decreased incidence of
      BPD. Randomized trials are needed to determine the efficacy and safety of early
      caffeine prophylaxis in VLBW infants.

PMID- 24461788
TI  - Van der woude syndrome (lip pit-cleft lip syndrome).

PMID- 24461789
TI  - Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T
      cells differentiation in children with 22q11.2 deletion syndrome.
AB  - OBJECTIVE: To perform an extensive analysis of the immune status of asymptomatic
      children with the 22q11.2 deletion syndrome, with special emphasis on the
      regulatory T cells (Treg) population. STUDY DESIGN: Analysis of thymic function,
      frequency and absolute counts of immune subsets, and phenotype of Treg were
      performed in 10 asymptomatic children bearing the 22q11.2 deletion and compared
      with 12 age-matched, healthy children. RESULTS: Children with 22q11.2 deletion
      syndrome showed a curtailed thymic output, lower T-cell levels, and a homeostatic
      deregulation in the CD4 T-cell compartment, characterized by a greater
      proliferative history in the naive CD4 T-cell subset. Treg numbers were markedly
      reduced in children with 22q11.2 deletion syndrome, and remaining Treg showed
      mostly an activated phenotype. CONCLUSIONS: Reduced thymic output in children
      with 22q11.2 deletion syndrome could be related with an increased proliferation
      in the naive CD4 T-cell compartment and the consequent Treg activation to ensure
      that T-cell expansion remains under control. Deregulated peripheral homeostasis
      and loss of suppressive capacity by Treg could compromise the integrity of T-cell
      immunity during adulthood and play a relevant role in the increased incidence of
      autoimmune diseases reported in patients with the 22q11.2 deletion syndrome.

PMID- 24461790
TI  - A case of infant botulism infection due to consumption of untreated well-water.
AB  - A 7-week-old boy with flaccid paralysis was diagnosed with infant botulism caused
      by Clostridium botulinum toxin type A. In this case of infant botulism, untreated
      well-water was identified as a potential source of this infection. 

PMID- 24461791
TI  - Bedside hemodynamic evaluation for neonates receiving respiratory support.

PMID- 24461792
TI  - Effect of intrauterine administration of gonadotropin releasing hormone with
      glycerol on serum LH concentrations in lactating dairy cows.
AB  - The objectives of the study were to assess: (1) preovulatory serum LH
      concentrations and (2) synchrony of ovulation after im or iu administration of
      GnRH with or without the addition of glycerol. Cows were presynchronized with 2
      injections of PGF2alpha given 14d apart (starting at 26+/-3DIM) followed by
      Ovsynch (OV; GnRH-7d-PGF2alpha-48h-GnRH) 12d later. At the time of the second
      GnRH of OV (GnRH2), cows were blocked by parity and randomly allocated to 1 of 4
      treatments: (1) control (CON; n=8) received 2mL of sterile water im; (2) im (IM;
      n=8) received 100MUg of GnRH im; (3) cows were infused with 200MUg GnRH into the
      uterus (IU; n=9); and (4) iu administration of 200MUg GnRH plus glycerol 7% v/v
      (IUG; n=8). Serum circulating progesterone concentrations at hour 0 did not
      differ (P>0.05) among groups. Concentrations of LH were greater (P<0.05) in IM
      than IU, IUG, and CON cows at hours 1, 1.5, 2, and 3. All cows ovulated within
      48h in the IM (8/8) group followed by IU (6/9) and IUG (4/8) groups, and only two
      out of eight cows ovulated in the CON group. Although iu administration of GnRH
      in the IU and IUG groups resulted in lower serum concentrations of LH than IM
      cows, IU or IUG cows were able to ovulate within 48h after GnRH2 administration. 

PMID- 24461793
TI  - [An exceptional presacral mass in children: rectal duplication].

PMID- 24461794
TI  - Effect of milk proteins on linear growth and IGF variables in overweight
      adolescents.
AB  - OBJECTIVE: Milk may stimulate growth acting via insulin-like growth factor-I (IGF
      I) secretion but the effect in adolescents is less examined. This study
      investigates the effect of milk proteins on linear growth, IGF-I, IGF binding
      protein-3 (IGFBP-3) and IGF-I/IGFBP-3 ratio in overweight adolescents. DESIGN:
      The trial included 193 overweight adolescents aged 12-15 years. They were
      randomized to drink 1L/day of: skimmed milk, whey, casein or water for 12 weeks;
      all milk-based drinks contained 35 g protein/L. A subgroup of 32 adolescents was
      examined 12 weeks before they were randomized into the groups and started the
      intervention (pre-test control group). Examinations included anthropometry, diet
      registration and blood samples which were analyzed for IGF-I and IGFBP-3 by
      chemiluminescence methods. The effects of milk-based drinks on linear growth, IGF
      I, IGFBP-3 and IGF-I availability, calculated as the IGF-I/IGFBP-3 ratio, were
      compared with baseline, the pre-test control group and water. RESULTS: IGF-I
      increased with skimmed milk (P=0.015) and tended to increase with casein
      (P=0.075) compared to the pre-test control group. IGFBP-3 but not IGF-I increased
      with skimmed milk (P=0.006) and casein (P=0.001) compared to water. There was no
      difference in height or height Z-score for any of the milk-based test drink
      groups compared to water or compared to the pre-test control group. However,
      height Z-score decreased within the whey group. CONCLUSIONS: Skimmed milk and
      casein may have a stimulating effect on the IGF-I system whereas there was no
      positive effect on height in overweight adolescents during this 12 week
      intervention.

PMID- 24461795
TI  - Ultrasound and neurophysiological correlation in common fibular nerve conduction
      block at fibular head.
AB  - OBJECTIVE: Ultrasound (US) and neurophysiological examination are useful tools in
      the evaluation of common fibular mononeuropathy. There is only a report comparing
      US and electrophysiological parameters in patients with common fibular nerve
      (CFN) conduction block at fibular head. We investigated the correlation between
      US and neurophysiologic findings in this condition. METHODS: We retrospectively
      reviewed patients with CFN assessed in our lab during last 2 years. Each patient
      underwent to clinical, neurophysiological and ultrasound evaluations. Cross
      sectional area (CSA) of CFN at fibular head was assessed. RESULTS: Twenty-four
      patients were included. Motor nerve conduction study showed a reduction of distal
      compound muscle action potential (CMAP) amplitude in 10 patients (mean 1.3 mV).
      US showed an increased CSA in 10 patients. Statistical analysis revealed a strong
      correlation between the increased CSA and the CMAP reduction of CFN. CONCLUSION:
      Our data suggest that usually US examination is normal in CFN conduction block at
      fibular head. However the association with axonal damage is frequently
      accompanied by an increase of CSA. SIGNIFICANCE: Ultrasound evaluation may
      represent a powerful diagnostic/prognostic tool in cases with CPN conduction
      block at fibular head because it usually shows normal pattern in pure conduction
      block and increase of CSA in associated axonal damage.

PMID- 24461796
TI  - Metabolic integrity of primary motor cortex may be compromised in clinically
      asymptomatic concussed athletes.

PMID- 24461797
TI  - Emotion perception and electrophysiological correlates in Huntington's disease.
AB  - OBJECTIVE: This study aimed to characterise, emotion perception deficits in
      symptomatic Huntington's disease (HD) via the use of event-related potentials
      (ERPs). METHODS: ERP data were recorded during a computerised facial expression
      task in 11 HD participants and 11 matched controls. Expression (scrambled,
      neutral, happy, angry, disgust) classification accuracy and intensity were
      assessed. Relationships between ERP indices and clinical disease characteristics
      were also examined. RESULTS: Accuracy was significantly lower for HD relative to
      controls, due to reduced performance for neutral, angry and disgust (but not
      happy) faces. Intensity ratings did not differ between groups. HD participants
      displayed significantly reduced visual processing amplitudes extending across pre
      face (P100) and face-specific (N170) processing periods, whereas subsequent
      emotion processing amplitudes (N250) were similar across groups. Face-specific
      and emotion-specific derivations of the N170 and N250 ('neutral minus scrambled'
      and 'each emotion minus neutral', respectively) did not differ between groups.
      CONCLUSIONS: Our data suggest that the facial emotion recognition performance
      deficits in HD are primarily related to neural degeneration underlying
      'generalised' visual processing, rather than face or emotional specific
      processing. SIGNIFICANCE: ERPs are a useful tool to separate functionally
      discreet impairments in HD, and provide an important avenue for biomarker
      application that could more-selectively track disease progression.

PMID- 24461798
TI  - Maxsim2 - Real-time interactive simulations for computer-assisted teaching of
      pharmacokinetics and pharmacodynamics.
AB  - We developed a computer program for use in undergraduate and graduate courses in
      pharmacology, pharmacokinetics and pharmacodynamics. This program can also be
      used in environmental and toxicological studies and preclinical simulation, to
      facilitate communication between modeling pharmacokineticists and project leaders
      or other decision-makers in the pharmaceutical industry. The program simulates
      the drug delivery and transport by means of (I) a six-compartment physiological
      pharmacokinetic flow model, (II) a system of traditional compartment models, or
      (III) a target-mediated drug disposition system. The program also can be used to
      simulate instantaneous equilibria between concentration and pharmacodynamic
      response, or as temporal delays between concentration and response. The latter is
      done by means of turnover models (indirect response models). Drug absorption,
      distribution, and elimination are represented by differential equations, which
      are described by organ and tissue volumes or other volumes of distribution, blood
      flows, clearance terms, and tissue-to-blood partition coefficients. The user can
      control and adjust these parameters by means of a slider in real time. By
      interactively changing the parameter values and simultaneously displaying the
      resulting concentration-time and/or response-time profiles, users can understand
      the major mechanisms that govern the disposition or the pharmacological response
      of the drug in the organism in real time. Schedule dependence is typically seen
      in clinical practice with a non-linear concentration-response relationship, and
      is difficult to communicate except via simulations. Here, we sought to illustrate
      the potential advantages of this approach in teaching pharmacology,
      pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-,
      and medical students or to project teams in drug discovery/development. 

PMID- 24461800
TI  - Overview of the International Myeloma Workshop 2013 Kyoto.

PMID- 24461799
TI  - Acceptability of robotic technology in neuro-rehabilitation: preliminary results
      on chronic stroke patients.
AB  - During the last decade, different robotic devices have been developed for motor
      rehabilitation of stroke survivors. These devices have been shown to improve
      motor impairment and contribute to the understanding of mechanisms underlying
      motor recovery after a stroke. The assessment of the robotic technology for
      rehabilitation assumes great importance. The aim of this study is to present
      preliminary results on the assessment of the acceptability of the robotic
      technology for rehabilitation on a group of thirty-four chronic stroke patients.
      The results from questionnaires on the patients' acceptability of two different
      robot-assisted rehabilitation scenarios show that the robotic approach was well
      accepted and tolerated by the patients. 

PMID- 24461801
TI  - Treatment of smoldering myeloma: early or delayed?

PMID- 24461802
TI  - Bench work for targeted therapy to the microenvironment of myeloma bone disease.

PMID- 24461803
TI  - Clinical contribution of PET/CT in myeloma: from the perspective of a
      radiologist.

PMID- 24461804
TI  - Vertebral fracture risk of multiple myeloma assessed by a CT-based finite element
      and trabecular structure analysis.

PMID- 24461805
TI  - Autologous stem cell transplantation for multiple myeloma in the era of novel
      agents.

PMID- 24461807
TI  - Prevalence of monoclonal gammopathy of undetermined significance in Asia: a
      viewpoint from nagasaki atomic bomb survivors.
AB  - Exposure to ionizing radiation is a known environmental risk factor for a variety
      of cancers including hematological malignancies, such as leukemia,
      myelodysplastic syndromes, and multiple myeloma. Therefore, for Hiroshima and
      Nagasaki atomic bomb survivors (surviving victims who were exposed to ionizing
      radiation emitted from the nuclear weapons), several cancer-screening tests have
      been provided annually, with government support, to detect the early stage of
      malignancies. An M-protein screening test has been used to detect multiple
      myeloma at an early stage among atomic bomb survivors. In the screening process,
      a number of patients with monoclonal gammopathy of undetermined significance
      (MGUS), in addition to multiple myeloma, have been identified. In 2009 and 2011,
      we reported the age- and sex-specific prevalence of MGUS between 1988 and 2004
      and the possible role of radiation exposure in the development of MGUS using the
      screening data of more than 1000 patients with MGUS among approximately 52,000
      Nagasaki atomic bomb survivors. The findings included: (1) a significant lower
      overall prevalence (2.1%) than that observed in Caucasian or African-origin
      populations; (2) a significantly higher prevalence in men than in women; (3) an
      age-related increase in the prevalence; (4) a significantly higher prevalence in
      people exposed to higher radiation doses only among those exposed at age 20 years
      or younger; and (5) a lower frequency of immunoglobulin M MGUS in Japanese
      patients than in patients in Western countries. The large study of MGUS among
      Nagasaki atomic bomb survivors has provided important findings for the etiology
      of MGUS, including a possible role of radiation exposure on the cause of MGUS and
      an ethnicity-related difference in the characteristics of MGUS. 

PMID- 24461808
TI  - Autologous stem cell transplantation for POEMS syndrome.

PMID- 24461809
TI  - The effect of the cognitive demands of the distraction task on unconscious
      thought.
AB  - The unconscious-thought effect occurs when distraction improves complex decision
      making. Recent studies suggest that this effect is more likely to occur with low-
      than high-demanding distraction tasks. We discuss implications of these findings
      for Newell & Shanks' (N&S's) claim that evidence is lacking for the intervention
      of unconscious processes in complex decision making. 

PMID- 24461811
TI  - Synthesis of stable Au-SiO2 composite nanospheres with good catalytic activity
      and SERS effect.
AB  - For improving stability and efficiency of noble metal nanomaterials, a
      straightforward one-step method was developed to synthesize Au-SiO2 composite
      nanospheres. Monodisperse hybrid silica nanospheres that had anilino-methyl on
      the surfaces were prepared first. The as-prepared hybrid silica nanospheres were
      then used to obtain Au nanocrystal through the redox reaction of HAuCl4 and
      anilino-methyl. This approach led to a better utilization of Au. By adjusting the
      surface morphologies and the particle sizes, the functional nanospheres displayed
      different surface-enhanced Raman scattering effects of Rhodamine 6G. The
      composite nanospheres showed high catalytic activity and good reusability in
      catalytic reduction of 4-nitrophenol because of their active gold surface. 

PMID- 24461810
TI  - Development of surgical techniques of secondary osteoplasty in cleft patients
      following 12 years experience.
AB  - PURPOSE: To evaluate the results of secondary osteoplasty in cleft patients, over
      a 12 years period, and to propose certain modifications and improvements of the
      cleft repair technique. MATERIALS AND METHODS: Data were retrieved for all young
      patients treated from 2000 to 2011. Patients were divided in 3 groups, of 4 years
      duration each; parameters registered among others included peri-operative
      orthodontics, type of graft used, techniques applied and revisions required until
      final repair. RESULTS: 65 patients (mean age 11.6 years) were included in the
      study. 80 cleft sites were treated. All clefts were finally repaired and bone
      continuity was achieved. Peri-operative orthodontics was applied in 84.6% of the
      cases. Bone grafts were harvested 60 times (84.5%) from the left anterior iliac
      crest and 11 times (15.5%) from the genial region of the mandible. During the 12
      years period ameliorations and changes were made at the recipient site, regarding
      the technique applied and the type of the graft. Revision operations for
      additional bone grafting were required in 6 cases in all (6/80 or 7.5% of the
      cleft sites). A gradual reduction of the number of revision osteoplasties was
      recorded in the 3 time periods, attributed to the improvements afore mentioned.
      CONCLUSIONS: Cleft bone repair, even in difficult bilateral cases, may be
      achieved with standardised preparation of the recipient site, adequate graft from
      the iliac crest, used in the form of both particulate bone and cortical plate on
      top, as well as full coverage of the graft.

PMID- 24461812
TI  - Study on the wetting transition of a liquid droplet sitting on a square-array
      cosine wave-like patterned surface.
AB  - A liquid droplet deposited on a hydrophobic surface with a square-array cosine
      wave-like pattern is simulated by using the Surface Evolver to study on the
      Cassie-Wenzel wetting transition. All the metastable states of a liquid drop with
      a fixed drop volume on the model surface are determined at different surface
      roughnesses. The maximum/minimum contact angles among the metastable states at
      each surface roughness correspond to the advancing/receding contact angles. It is
      interesting to find out that when the surface roughness is slightly smaller than
      the transition roughness (between the Wenzel and Cassie states) the drop under
      the condition of the advancing and receding contact angle would exhibit the
      Cassie and Wenzel state, respectively. Both experimental and simulation results
      demonstrate that a liquid droplet of a fixed volume on patterned substrates may
      exhibit either the Wenzel state or the Cassie state at a certain surface
      roughness. An increase in the surface roughness may induce the wetting transition
      from the Wenzel state to the Cassie state to occur. The slip-jump behavior of an
      advancing contact line with increasing drop volume at different viewing angles is
      carefully discussed to demonstrate the distorted three-phase contact line. Effect
      of surface roughness and drop size on liquid penetration into groove of the model
      surface is discussed. 

PMID- 24461813
TI  - Lyso-phosphatidylcholines in Langmuir monolayers--influence of chain length on
      physicochemical characteristics of single-chained lipids.
AB  - Single-chained phospholipids constitute a class of membrane components found in
      normal cells in relatively low concentration; however, these group of compounds
      are known owing to their broad physiological activities. Despite that the
      knowledge concerning fundamental physicochemical properties of lyso-lipids is
      very limited and in contrast to double-chained phospholipids there is an obvious
      deficiency of studies focused on correlation between their amphipathic character
      and film-forming properties with biological activities. In the present paper we
      have attempted to explain the main issues regarding the characteristics of lyso
      PCs in monolayers at the air/aqueous interface. Our results show that all the
      investigated phospholipids differing in the length of hydrophobic chain: C18lyso
      PC, C22lyso-PC and C24lyso-PC form stable Langmuir monolayers of a relatively low
      degree of condensation. It was found that during compression the investigated
      monolayers significantly change their organization at the interface which is
      strongly connected with temperature of the subphase. The application of X-ray
      reflectivity confirmed that the bulky choline head-groups in molecules of lyso
      PCs are strongly penetrated by water molecules, while the hydrophobic chains are
      significantly tilted from the surface normal. The obtained results show that the
      phase transitions observed in the course of the registered isotherms result from
      decrease in immersion of molecules in the subphase as well as from the decrease
      in hydrating water molecules. On the basis of GIXD experiments it turned out that
      in the monolayers of C22lyso-PC and C24lyso-PC at higher surface pressures (>20
      mN/m) small fractions of periodically ordered phase appear at the interface. For
      the monolayer of C24lyso-PC in the periodically ordered fraction the untilted (U)
      to tilted (t) phase transition was found.

PMID- 24461814
TI  - Control of gold nanoparticles based on circular DNA strand displacement.
AB  - In this study, DNA strand displacement is utilized to control the aggregation of
      DNA/gold nanoparticles (AuNPs) based on circular DNA, in which DNA/AuNP
      conjugates are captured and released by adding different DNA signal strands.
      Using this strategy, single DNA/nanoparticle building blocks are capable of
      assembling into complex structures of two and three circular DNA/nanoparticles.
      The existence of these structures is demonstrated by gel electrophoresis and
      transmission electron microscopy (TEM) analysis. This advance has potential
      applications in controlling, transporting and detecting DNA/AuNP conjugates with
      subsequent manipulation of the structure and function of these assemblies. 

PMID- 24461815
TI  - Liquid-phase exfoliation of graphene in organic solvents with addition of
      naphthalene.
AB  - We report a facile method for the production of graphene sheets through liquid
      phase exfoliation of graphite in organic solvents with addition of naphthalene.
      The production yield of graphene is significantly increased with the addition of
      naphthalene in most solvents tested in this work. Naphthalene serves as a
      "molecular wedge" to intercalate into the edge of graphite, which plays a key
      role during sonication and significantly improves the production yield of
      graphene. The graphene concentration of the dispersion in 1-methyl-2
      pyrrolidinone is as high as 0.15 mg/mL (after sonication for 90 min), which
      allows this method to easily produce films and composites for a range of
      applications.

PMID- 24461816
TI  - Dual colorimetric response of polydiacetylene/zinc oxide nanocomposites to low
      and high pH.
AB  - This contribution presents our continuation work on the color-transition
      behaviors of polydiacetylene(PDA)/ZnO nanocomposites prepared by using three
      types of monomers, 5,7-hexadecadiynoic acid (HDDA), 10,12-tricosadiynoic acid
      (TCDA) and 10,12-pentacosadiynoic acid (PCDA). The color-transition behaviors of
      these nanocomposites upon exposure to acid and base are investigated by utilizing
      UV/vis absorption spectroscopy. We have found that these PDA/ZnO nanocomposites
      exhibit colorimetric response at both low and high pH regions. The addition of
      acid causes the poly(HDDA)/ZnO, poly(TCDA)/ZnO and poly(PCDA)/ZnO nanocomposites
      to change color from blue to red at pH~5, 3.5 and 2, respectively. The color of
      pure PDA vesicles, on the other hand, is hardly affected at this pH range. At
      high pH region, the pure poly(TCDA) vesicles change color at pH~8 while it
      requires much higher pH to induce color transition of the PDA/ZnO nanocomposites.
      The mechanism responsible for color transition of the PDA/ZnO nanocomposites is
      explored by various techniques including infrared spectroscopy, zeta potential
      analyzer and light scattering. Our result provides a new approach for controlling
      the colorimetric response to pH of PDA-based materials.

PMID- 24461818
TI  - Monodispersed mesoporous silica spheres with various mesopore symmetries.
AB  - Monodispersed mesoporous silica spheres (MMSS) with different mesopore
      symmetries, such as hexagonal, cubic, or the mixture of hexagonal/cubic, are
      synthesized changing synthesis conditions. It seems that the direction of
      mesopores is retained through the particle in MMSS with cubic symmetry. In the
      case of hexagonal/cubic mixed symmetry, cubic structure is observed at the center
      of the particle, while hexagonal structure is observed near the surface. It is
      assumed that cubic structure forms at early stage of the particle growth and
      hexagonal symmetry forms at the later stage, leading to the formation of cubic
      core/hexagonal shell structure. 

PMID- 24461819
TI  - Molecular dynamics simulation of adsorption of pyrene-polyethylene glycol onto
      graphene.
AB  - The nonvalent interaction between amphiphilic polymers and graphenes is important
      to provide the surface functionalization of graphene. Herein, molecular dynamics
      simulations were carried out to investigate the interaction of pyrene
      polyethylene glycol (Py-PEG) with graphene. The dynamic adsorption process and
      self-assembly morphology of Py-PEG onto nanoscale graphene surface have been
      demonstrated. The effects of the graphene size and the length of polymer chain
      were explored. It was shown that Py-PEG could spontaneously adsorb onto graphene
      surface. The Py-PEG polymer generally exhibits a coil structure with the
      hydrophobic pyrene surrounded by the PEG chain. However, once the Py-PEG molecule
      approaches the graphene surface, the PEG chain can unfold its structure on the
      graphene surface and the pyrene group can display a flat binding mode with the
      surface. Comparatively, the water solvent has an obvious impeding effect on the
      surface adsorption due to the hydrogen bonding interaction between PEG chain and
      water molecules. The thermodynamic free energy shows that the interaction between
      pyrene and carbon surface provides the main interaction contribution to the
      adsorption performance. 

PMID- 24461817
TI  - Direct interaction of hydrophilic gold nanoparticles with dexamethasone drug:
      loading and release study.
AB  - Water-soluble gold nanoparticles functionalized by sodium 3-mercapto-1
      propansulfonate (Au-3MPS) were synthesized with different Au/thiol molar ratios
      for their ability to interact with biomolecules. In particular, a synthetic
      glucocorticoid steroid, i.e. dexamethasone (DXM) was selected. Herein, the
      formation of the Au-3MPS/DXM bioconjugate is reported. Au-3MPS nanoparticles show
      a plasmon resonance at 520 nm, have a spherical morphology and average size of 7
      10 nm. The total number of gold atoms was estimated to be about 10600, with a
      surface component of 8800 atoms and a number of thiol ligands of about 720,
      roughly one anchored thiol every 10 surface gold atoms. The drug-nanoparticle
      interaction occurs through the fluorine atom of DXM and Au(I) atoms on the gold
      nanoparticle surface. The 3MPS ligands closely pack apart each other to leave
      room for the DXM, that lies at the gold surface in an unusual, almost parallel
      feature. The loading efficiency of DXM on Au-3MPS was assessed in the range 70
      80%, depending on the thiol content. Moreover, our studies confirmed the drug
      release of about 70% in 5 days. Thanks to their unique properties, i.e. high
      water solubility, small size and almost monodispersity, Au-3MPS display high
      potential in biotechnological and biomedical applications, mainly for the loading
      and release of water insoluble drugs.

PMID- 24461820
TI  - Facile synthesis of hierarchical and porous V2O5 microspheres as cathode
      materials for lithium ion batteries.
AB  - Hierarchical and porous V2O5 microspheres have been fabricated by a refluxing
      approach followed by annealing in air. The resulting porous V2O5 microspheres
      typically have diameters of 3-6 MUm and are constructed of intertwined laminar
      nanocrystals or crosslinked nanobricks. It is found that the vanadyl glycolates
      rinsed with water have pronounced pore structures than that rinsed with ethanol
      alone. In addition, the configuration of the vanadyl glycolates microspheres can
      be tuned during the refluxing along with stirring. The possible formation
      processes of the vanadyl glycolates and V2O5 products have been discussed based
      on the experimental data. Electrochemical tests indicate that the hierarchical
      and porous V2O5 microspheres exhibit relatively high and stable Li(+) storage
      properties. The porous V2O5 microspheres assembled by intertwined nanoparticles
      maintain reversible Li(+) storage capacities of 102 and 80 mAh g(-1),
      respectively; whilst the porous V2O5 microspheres assembled by crosslinked
      nanobricks maintain reversible Li(+) storage capacities of 100 and 85 mAh g(-1)
      over 100 cycles at current rates of 0.5 and 1 C, respectively. The superior Li(+)
      storage performance of the hierarchical and porous V2O5 microspheres could mainly
      be ascribed to the improved electrode/electrolyte interface, reduced Li(+)
      diffusion paths, and relieved volume variation during lithiation and delithiation
      processes.

PMID- 24461821
TI  - Encapsulation of pristine fullerene C60 within block copolymer micelles through
      interfacial instabilities of emulsion droplets.
AB  - We report a facile and versatile strategy to encapsulate pristine fullerene (C60)
      within spherical or wormlike block copolymer micelles through interfacial
      instability of emulsion droplets. C60 and amphiphilic block copolymer polystyrene
      b-poly(ethylene oxide) were firstly dispersed in chloroform. The resulting
      solution was emulsified with aqueous sodium dodecylsulfate solution by simply
      shaking it. The emulsion droplets were collected in an open container and the
      solvent was allowed to evaporate. During solvent evaporation, the emulsion
      droplets became unstable and broke into tiny droplets, i.e., interfacial
      instabilities occurred, triggering the formation of uniform spherical micelles
      with encapsulated fullerenes in the micellar cores. More interestingly, fullerene
      addition induced a morphological transition from cylindrical micelles to string
      of-vesicles and then to spherical micelles with increasing fullerene contents of
      5 wt%, 10 wt%, and 30 wt%, respectively. We show that the optical properties of
      the confined C60 molecules can be modified by varying the quantity of fullerenes
      in the micelles. In addition, poly(3-hexylthiophene) (P3HT) can be co
      encapsulated with C60 into the micellar cores when P3HT was dissolved in the
      initial polymer solution prior to emulsification. Presence of C60 in the micellar
      cores induced fluorescence quenching of P3HT due to photoinduced energy transfer
      from electron-donating P3HT to electron-accepting C60 molecules. Hybrid micelles
      with well-controlled structures and components can be potentially useful in the
      area of photodynamic therapy and photovoltaics.

PMID- 24461822
TI  - Au nanoplates as robust, recyclable SERS substrates for ultrasensitive chemical
      sensing.
AB  - With the structural advantages of being sharp and straight, Au nanoplates may
      work as a promising surface-enhanced Raman scattering (SERS) platform for
      detection of Raman-sensitive analytes. However, the utilization of Au nanoplates
      as realistic SERS substrates is still not widely investigated, especially in the
      practical detection of environmentally persistent pollutants. This work delivers
      the first successful demonstration of using Au nanoplate platform in practical
      SERS sensing toward a typical polycyclic aromatic hydrocarbons pollutant of
      pyrene. The samples were prepared using an environmentally benign seed-mediated
      growth approach without the post-purification treatment. It was found that Au
      nanoplates exhibited significantly enhanced SERS activities (enhancement
      factor=7.30*10(7)) and achieved an extremely low detection limit (5*10(-10) M)
      toward pyrene molecules. Furthermore, the SERS activity of Au nanoplates can be
      fully recovered after repeatedly used and recycled in pyrene detection. These
      results manifest that the present Au nanoplates can serve as robust, recyclable
      SERS substrates that allow rapid detection of trace levels of analytes with a
      high degree of sensitivity and stability. The findings from this work may
      facilitate the use of Au nanoplate SERS substrates in more realistic applications
      such as biomolecule sensing and environmental monitoring.

PMID- 24461823
TI  - A drag reducing surfactant threadlike micelle system with unusual rheological
      responses to pH.
AB  - A pH-responsive threadlike micellar system was developed by mixing alkyl bis(2
      hydroxyethyl)methylammonium chloride (EO12) and trans-o-coumaric acid (tOCA). The
      rheological response of this system to pH is unusual in that it has
      viscoelasticity at both high and low pH levels, while it shows water-like
      behaviors at medium pH. Cryogenic transmission electron microscopy (Cryo-TEM)
      images confirmed the presence of TLMs at pH 3.5 and pH 9.8. This system also had
      DR (drag reduction) capability at low and high pH. The unusual rheological and
      micellar responses of this system to pH are caused by the dual pK(a)'s of tOCA.
      (1)H NMR and zeta potential results support this hypothesis.

PMID- 24461824
TI  - Size histograms of gold nanoparticles measured by gravitational sedimentation.
AB  - Sedimentation curves of gold nanoparticles in water were obtained by measuring
      the optical density of a suspension over time. The results are not subject to
      sampling errors, and refer to the particles in situ. Curves obtained
      simultaneously at several wave lengths were analyzed together to derive the size
      histogram of the sedimenting particles. The bins in the histogram were 5 nm wide
      and centered at diameters 60, 65, ..., 110 nm. To get the histogram, we weighted
      previously calculated solutions to the Mason-Weaver sedimentation-diffusion
      equation for various particle diameters with absorption/scattering coefficients
      and size (diameter) abundances {c(j)}, and found the {c(j)} which gave the best
      fit to all the theoretical sedimentation curves. The effects of changing the
      number of bins and the wave lengths used were studied. Going to smaller bins
      would mean determining more parameters and require more wave lengths. The
      histograms derived from sedimentation agreed quite well in general with the
      histogram derived from TEM. Differences found for the smallest particle diameters
      are partly due to statistical fluctuations (TEM found only 1-2 particles out of
      103 with these diameters). More important is that the TEM histogram indicates 12%
      of the particles have diameters of 75+/-2.5 nm, and the sedimentation histogram
      shows none. We show that this reflects the difference between the particles in
      situ, which possess a low-density shell about 1 nm thick, and the bare particles
      on the TEM stage. Correcting for this makes agreement between the two histograms
      excellent. Comparing sedimentation-derived with TEM-derived histograms thus shows
      differences between the particles in situ and on the TEM stage.

PMID- 24461825
TI  - Removal of the surfactant sodium dodecylbenzenesulfonate from water by processes
      based on adsorption/bioadsorption and biodegradation.
AB  - This study analyzed the bioadsorption/biodegradation kinetics of the surfactant
      sodium dodecylbenzenesulfonate (SDBS) on commercial activated carbons and on
      activated carbons prepared in the laboratory by activation of almond shells. The
      effect of surface oxygen species on these processes was also investigated by
      using an activated carbon from almond shells oxidized with H2O2 or HNO3. SDBS
      removal kinetics followed a first-order kinetic model, with rate constants
      between 1.25*10(-2) h(-1) and 2.14*10(-2) h(-1). The removal rate constants of
      total organic carbon (TOC) were also determined, obtaining values ranging between
      0.51*10(-2) h(-1) and 1.76*10(-2) h(-1). TOC removal rate constants were lower
      than SDBS removal rate constants, demonstrating that SDBS is also biodegraded
      during bioadsorption. Both the inorganic carbon concentration and the colony
      forming units confirm this biodegradation. The amount of SDBS removed from water
      varies between 109.0 and 232.3 mg SDBS/g of carbon. When SDBS adsorption on
      activated carbon is conducted in the presence of bacteria, which is the real
      situation in water treatment plants, a fraction of bacteria are adsorbed on the
      surface of activated carbon. A part of the SDBS is removed by adsorption
      (bioadsorption) and other part by biodegradation.

PMID- 24461826
TI  - Carboxyl decorated Fe3O4 nanoparticles for MRI diagnosis and localized
      hyperthermia.
AB  - We report the development of carboxyl decorated iron oxide nanoparticles (CIONs)
      by a facile soft-chemical approach for magnetic resonance imaging (MRI) and
      hyperthermia applications. These superparamagnetic CIONs (~10 nm) are resistant
      to protein adsorption under physiological medium and exhibit good colloidal
      stability, magnetization and cytocompatibility with cell lines. Analysis of the
      T2-weighted MRI scans of CIONs in water yields a transverse relaxivity (r2) value
      of 215 mM(-1) s(-1). The good colloidal stability and high r2 value make these
      CIONs as promising candidates for high-efficiency T2 contrast agent in MRI.
      Further, these biocompatible nanoparticles show excellent self-heating efficacy
      under external AC magnetic field (AMF). The infrared thermal imaging confirmed
      the localized heating of CIONs under AMF. Thus, these carboxyl decorated Fe3O4
      nanoparticles can be used as a contrast agent in MRI as well as localized heat
      activated killing of cancer cells. Furthermore, the active functional groups
      (COOH) present on the surface of Fe3O4 nanoparticles can be accessible for
      routine conjugation of biomolecules/drugs through well-developed bioconjugation
      chemistry.

PMID- 24461828
TI  - Highly sensitive and selective determination of pyrazinamide at poly-L
      methionine/reduced graphene oxide modified electrode by differential pulse
      voltammetry in human blood plasma and urine samples.
AB  - In this current study we used electrochemically active film which contains poly-L
      methionine (PMET) and electrochemically reduced graphene oxide (ERGO) on glassy
      carbon electrode (GCE) for pyrazinamide (PZM) detection. The electrocatalytic
      response of analyte at PMET/ERGO/GCE film was measured using both cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV). In addition,
      electrochemical impedance studies revealed that the smaller R(ct) value observed
      at PMET/ERGO film modified GCE which authenticates its good conductivity and
      faster electron transfer rate. The prepared PMET/ERGO/GCE film exhibits excellent
      DPV response towards PZM and the reduction peak current increased linearly with
      respect to PZM concentration in the linear range between 0.4 MUM to 1129 MUM with
      a sensitivity of 0.266 MUA MUM(-1) cm(-2). Real sample studies were carried out
      in human blood plasma and urine samples, which offered good recovery and revealed
      the promising practicality of the sensor for PZM detection. The proposed sensor
      displayed a good selectivity, repeatability, sensitivity with appreciable
      consistency and good reproducibility. In addition, the proposed electrochemical
      sensor showed good results towards the commercial pharmaceutical PZM samples.

PMID- 24461827
TI  - Preparation of cellulose particles using an ionic liquid.
AB  - Cellulose is a ubiquitous natural fiber used in various industrial materials and
      applications. We prepared micron-sized cellulose particles by the solvent
      releasing method (SRM) in which cellulose-[Bmim]Cl-N,N-dimethylformamide (DMF)
      droplets are dispersed in hexadecane (HD) containing dissolved surfactant. The
      dispersion is then poured into a large amount of 1-butanol. Since 1-butanol is
      miscible with HD, [Bmim]Cl, and DMF but not with cellulose, the cellulose
      particles precipitate out. FTIR and (1)H NMR analyses confirmed that this
      technique precipitated cellulose and completely removed [Bmim]Cl and DMF from the
      cellulose-[Bmim]Cl-DMF droplets. Interestingly, the obtained cellulose particles
      were almost the same size as the original droplets (cellulose, 7 wt%), indicating
      a microporous structure of the cellulose particles with a large medium content.
      Although the microporous structure collapsed as the medium evaporated, it was
      maintained by a freeze-drying technique.

PMID- 24461829
TI  - Adsorption of Aerosol-OT at the calcite/water interface--comparison of the sodium
      and calcium salts.
AB  - The adsorption of the surfactant Aerosol-OT (AOT) at the calcite-water interface
      has been investigated using batch adsorption isotherms and neutron reflection.
      The adsorption isotherms showed that NaAOT adsorption followed S-type adsorption
      behaviour with a maximum surface excess of 2.5 mg m(-2) but the method could not
      be used for the investigation of Ca(AOT)2 adsorption owing to the changes in the
      bulk phase behaviour of the solution. The surface excess, determined by neutron
      reflection at the critical micelle concentration (CMC), was 2.5 mg m(-2) for
      Ca(AOT)2 and 1.8 mg m(-2) for NaAOT. The time dependence of the NaAOT adsorption
      suggests a slow conversion from the sodium to the calcium salt of AOT at the
      calcite-water interface by binding calcium ions released from the slightly
      soluble calcite. The layer thickness in both cases was 35 A which indicates
      adsorption as bilayers or distorted micelles. At higher concentrations of NaAOT
      (~10* CMC) adsorption of an AOT lamellar phase was evident from Bragg peaks in
      the specular reflection. To our knowledge, this is the first time that adsorption
      of a surfactant at the calcite-water interface has been investigated by neutron
      reflection. The technique provided significant new insight into the adsorption
      behaviour of AOT which would not have been accessible using traditional
      techniques.

PMID- 24461830
TI  - Surface complexation modeling of Hg(II) adsorption at the goethite/water
      interface using the charge distribution multi-site complexation (CD-MUSIC) model.
AB  - HYPOTHESIS: Previous attempts to describe Hg(II) adsorption onto mineral surfaces
      using surface complexation models (SCMs) have proven unsuccessful and/or require
      the use of hypothetical surface species. Given that metal ion adsorption at the
      mineral-water interface is greatly influenced by mineral surface heterogeneity
      and the presence of competing adsorbates in solution, it stands to reason that
      estimating the crystal face composition (CFC) of the mineral surface and the
      extent of carbonate contamination in the experimental system will improve SCM
      predictions. EXPERIMENTS: The Charge Distribution Multi-Site Complexation (CD
      MUSIC) model was used to simulate experimental Hg(II) adsorption data, collected
      on the iron hydroxide mineral goethite, in the presence and absence of competing
      adsorbates and complexing ligands as a function of pH and ionic strength. The CFC
      of each goethite sample studied was predicted using a newly discovered
      relationship between goethite's proton reactive site density (N(H)) and specific
      surface area (SSA). Carbonate's presence in the experimental systems was
      determined utilizing a novel methodology developed in this work. FINDINGS: The CD
      MUSIC model developed in this study accurately predicted Hg(II) adsorption onto
      goethite over the entire range of experimental conditions investigated while only
      employing surface species consistent with spectroscopic evidence.

PMID- 24461831
TI  - Glass capillary microfluidics for production of monodispersed poly (DL-lactic
      acid) and polycaprolactone microparticles: experiments and numerical simulations.
AB  - HYPOTHESIS: Droplet size in microfluidic devices is affected by wettability of
      the microfluidic channels. Three-dimensional countercurrent flow focusing using
      assemblies of chemically inert glass capillaries is expected to minimize wetting
      of the channel walls by the organic solvent. EXPERIMENTS: Monodispersed
      polycaprolactone and poly(lactic acid) particles with a diameter of 18-150 MUm
      were produced by evaporation of solvent (dichloromethane or 1:2 mixture of
      chloroform and toluene) from oil-in-water or water-in-oil-in-water emulsions
      produced in three-dimensional flow focusing glass capillary devices. The drop
      generation behaviour was simulated numerically using the volume of fluid method.
      FINDINGS: The numerical results showed good agreement with high-speed video
      recordings. Monodispersed droplets were produced in the dripping regime when the
      ratio of the continuous phase flow rate to dispersed phase flow rate was 5-20 and
      the Weber number of the dispersed phase was less than 0.01. The porosity of
      polycaprolactone particles increased from 8 to 62% when 30 wt% of the water phase
      was incorporated in the organic phase prior to emulsification. The inner water
      phase was loaded with 0.156 wt% lidocaine hydrochloride to achieve a sustained
      drug release. 26% of lidocaine was released after 1 h and more than 93% of the
      drug was released after 130 h.

PMID- 24461832
TI  - Fabrication of hierarchical core-shell Au@ZnO heteroarchitectures initiated by
      heteroseed assembly for photocatalytic applications.
AB  - Three dimensional dandelion-like hierarchical core-shell Au@ZnO
      heteroarchitectures with ZnO nanorods grown radially on Au nanoparticle (NP)
      cores have been successfully prepared with a high yield via a simple solution
      method involving heteroseed-induced nucleation and subsequent heteroepitaxial
      growth processes. Briefly, mercaptopropionic acid (MA) modified Au NPs were
      synthesized beforehand and served as nucleation centers for primary ZnO seed
      generation and Au@ZnO heteroseed formation. Then an epitaxial growth of ZnO
      nanorods (ZnO NRs) on the Au@ZnO heteroseeds resulted in the formation of Au@ZnO
      dandelions. The photocatalytic properties of as-prepared Au@ZnO dandelions were
      evaluated through rhodamine B (RhB) photodegradation under UV irradiation. The
      result showed that the Au@ZnO dandelions had improved photocatalytic performance
      compared with pure ZnO NRs and hybrids of ZnO NRs/Au NPs, due likely to the
      synergistic effect of the metal-semiconductor heterojunction and the unique
      dandelion-like hierarchical core-shell structure. 

PMID- 24461833
TI  - Molecular dynamics simulations of silver nanocluster supported on carbon
      nanotube.
AB  - We carried out molecular dynamics simulations to examine the thermal, structural
      and dynamics properties of single walled carbon nanotube-supported silver
      nanoclusters with N=38, 108 and 256 atoms. The nanoclusters were simulated in two
      stages: first heated in 100-1700 K temperature range with steps of 100 K, then
      cooled to 100 K with the same steps. The number of Ag atoms in nanocluster layer
      in contact with the nanotube surface, the height of nanocluster and diameter of
      the lowest layer (layer in contact with nanotube) were calculated as a function
      of time. Also, the hysteresis in potential curves, surface melting,
      irreversibility of structural change with temperature, broaden interface
      structure and surface wetting were identified by analyzing the obtained data from
      simulations.

PMID- 24461834
TI  - Core/shell, protuberance-free multiwalled carbon nanotube/polyaniline
      nanocomposites via interfacial chemistry of aryl diazonium salts.
AB  - Highly uniform core-shell like multi-walled carbon nanotubes-polyaniline (MWCNT
      PANI) nanocomposites were prepared in two steps (i) surface modification of
      MWCNTs with a 4-aminodiphenylamine group via in situ diazonium generation
      process; and (ii) polymerization of aniline onto surface modified MWCNTs. This
      functionalization helped to easily disperse the MWCNTs in acidic solutions; hence
      it is suitable for the chemical oxidative polymerization of aniline. It was found
      that MWCNT-PANI nano-composites with higher MWCNTs loading yield PANI chains with
      more quinoid units than the pure PANI, which results in significant improvement
      in the conductivity of the composites. This facile approach of synthesizing core
      shell nanocomposites highlights the efficiency of the interfacial chemistry of
      aryl diazonium salts in generating conductive polymer/MWCNT nanocomposites with
      enhanced conductivity and high surface area. 

PMID- 24461835
TI  - Catalytically active and hierarchically porous SAPO-11 zeolite synthesized in the
      presence of polyhexamethylene biguanidine.
AB  - Hierarchically porous SAPO-11 zeolite (H-SAPO-11) is rationally synthesized from
      a starting silicoaluminophosphate gel in the presence of polyhexamethylene
      biguanidine as a mesoscale template. The sample is well characterized by XRD, N2
      sorption, SEM, TEM, NMR, XPS, NH3-TPD, and TG techniques. The results show that
      the sample obtained has good crystallinity, hierarchical porosity (mesopores at
      ca. 10 nm and macropores at ca. 50-200 nm), high BET surface area (226 m(2)/g),
      large pore volume (0.25 cm(3)/g), and abundant medium and strong acidic sites
      (0.36 mmol/g). After loading Pt (0.5 wt.%) on H-SAPO-11 by using wet impregnation
      method, catalytic hydroisomerization tests of n-dodecane show that the
      hierarchical Pt/SAPO-11 zeolite exhibits high conversion of n-dodecane and
      enhanced selectivity for branched products as well as reduced selectivity for
      cracking products, compared with conventional Pt/SAPO-11 zeolite. This phenomenon
      is reasonably attributed to the presence of hierarchical porosity, which is
      favorable for access of reactants on catalytically active sites. The improvement
      in catalytic performance in long-chain paraffin hydroisomerization over Pt/SAPO
      11-based catalyst is of great importance for its industrial applications in the
      future.

PMID- 24461836
TI  - Energy from CO2 using capacitive electrodes--theoretical outline and calculation
      of open circuit voltage.
AB  - Recently, a new technology has been proposed for the utilization of energy from
      CO2 emissions (Hamelers et al., 2014). The principle consists of controlling the
      dilution process of CO2-concentrated gas (e.g., exhaust gas) into CO2-dilute gas
      (e.g., air) thereby extracting a fraction of the released mixing energy. In this
      paper, we describe the theoretical fundamentals of this technology when using a
      pair of charge-selective capacitive electrodes. We focus on the behavior of the
      chemical system consisting of CO2 gas dissolved in water or monoethanolamine
      solution. The maximum voltage given for the capacitive cell is theoretically
      calculated, based on the membrane potential. The different aspects that affect
      this theoretical maximum value are discussed. 

PMID- 24461837
TI  - Chitosan-coated mesoporous microspheres of calcium silicate hydrate:
      environmentally friendly synthesis and application as a highly efficient
      adsorbent for heavy metal ions.
AB  - Chitosan-coated calcium silicate hydrate (CSH/chitosan) mesoporous microspheres
      formed by self-assembly of nanosheets have been synthesized in aqueous solution
      under ambient conditions without using any toxic surfactant or organic solvent.
      The method reported herein has advantages of simplicity, low cost and being
      environmentally friendly. The BET specific surface area of CSH/chitosan
      mesoporous microspheres is measured to be as high as ~356 m(2) g(-1), which is
      considerably high among calcium silicate materials. The as-prepared CSH/chitosan
      mesoporous microspheres are promising adsorbent and exhibit a quick and highly
      efficient adsorption behavior toward heavy metal ions of Ni(2+), Zn(2+), Cr(3+),
      Pb(2+) Cu(2+) and Cd(2+) in aqueous solution. The adsorption kinetics can be well
      fitted by the pseudo second-order model. The maximum adsorption amounts of
      Ni(2+), Zn(2+), Pb(2+), Cu(2+) and Cd(2+) on CSH/chitosan mesoporous microspheres
      are extremely high, which are 406.6, 400, 796, 425 and 578 mg/g, respectively.
      The CSH/chitosan adsorbent exhibits the highest affinity for Pb(2+) ions among
      five heavy metal ions. The adsorption capacities of the CSH/chitosan adsorbent
      toward heavy metal ions are relatively high compared with those reported in the
      literature.

PMID- 24461838
TI  - Synthesis of phenolic precursor-based porous carbon beads in situ dispersed with
      copper-silver bimetal nanoparticles for antibacterial applications.
AB  - Copper (Cu) and silver (Ag) bimetal-dispersed polymeric beads (~0.7 mm) were
      synthesized by suspension polymerization using phenol and formaldehyde monomers.
      The Cu:Ag bimetal nanoparticles (Nps) were incorporated into the polymeric matrix
      at the incipience of gel formation during polymerization using an anionic
      surfactant. The prepared bimetal-doped polymeric beads were carbonized, activated
      using steam, and reduced in a hydrogen atmosphere to produce metal Nps-doped
      porous carbon beads. The prepared bimetal (Cu and Ag) Nps-doped beads exhibited
      significantly larger anti-bacterial activities than single-(Cu or Ag) metal-doped
      beads for both gram-positive Staphylococcus aureus and gram-negative Escherichia
      coli bacteria. The prepared materials contained the total optimized amounts of Cu
      and Ag. These amounts were smaller (approximately half) than the amount of single
      metal (Cu or Ag) required for preparing single-metal-doped beads. Although Cu Nps
      exhibit lesser antibacterial activity than Ag Nps, it enhanced the porosity of
      the beads. The prepared bimetal beads remained effective for 120 h, completely
      inhibiting the bacterial growth, and therefore, they are potential antibacterial
      agents for water purification.

PMID- 24461839
TI  - Formation of monodisperse mesoporous silica microparticles via spray-drying.
AB  - In this work, a protocol to synthesize monodisperse mesoporous silica
      microparticles via a unique microfluidic jet spray-drying route is reported for
      the first time. The microparticles demonstrated highly ordered hexagonal
      mesostructures with surface areas ranging from ~900 up to 1500 m(2)/g and pore
      volumes from ~0.6 to 0.8 cm(3)/g. The particle size could be easily controlled
      from ~50 to 100 MUm from the same diameter nozzle via changing the initial solute
      content, or changing the drying temperature. The ratio of the surfactant (CTAB)
      and silica (TEOS), and the amount of water in the precursor were found to affect
      the degree of ordering of mesopores by promoting either the self-assembly of the
      surfactant-silica micelles or the condensation of the silica as two competing
      processes in evaporation induced self-assembly. The drying rate and the curvature
      of particles also affected the self-assembly of the mesostructure. The particle
      mesostructure is not influenced by the inlet drying temperature in the range of
      92-160  degrees C, with even a relatively low temperature of 92  degrees C
      producing highly ordered mesoporous microparticles. The spray-drying derived
      mesoporous silica microparticles, while of larger sizes and more rapidly
      synthesized, showed a comparable performance with the conventional mesoporous
      silica MCM-41 in controlled release of a dye, Rhodamine B, indicating that these
      spray dried microparticles could be used for the immobilisation and controlled
      release of small molecules.

PMID- 24461840
TI  - Synthesis, characterization and optical properties of an amino-functionalized
      gold thiolate cluster: Au10(SPh-pNH2)10.
AB  - Research interest in ultra small gold thiolate clusters has been rising in recent
      years for the challenges they offer to bring together properties of nanoscience
      and well-defined materials from molecular chemistry. Here, a new atomically well
      defined Au10 gold nanocluster surrounded by ten 4-aminothiophenolate ligands is
      reported. Its synthesis followed the similar conditions reported for the
      elaboration of Au144(SR)60, but because the reactivity of thiophenol ligands is
      different from alkanethiol derivates, smaller Au10 clusters were formed.
      Different techniques, such as ESI-MS, elemental analysis, XRD, TGA, XPS and UV
      vis-NIR experiments, have been carried out to determine the Au10(SPh-pNH2)10
      formula. Photoemission experiment has been done and reveals that the Au10
      clusters are weakly luminescent as opposed to the amino-based ultra-small gold
      clusters. This observation points out that the emission of gold thiolate clusters
      is highly dependent on both the structure of the gold core and the type of the
      ligands at the surface. In addition, ultra-small amino-functionalized clusters
      offer the opportunity for extended work on self-assembling networks or deposition
      on substrates for nanotechnologies or catalytic applications. 

PMID- 24461841
TI  - Redox reactivity of cerium oxide nanoparticles against dopamine.
AB  - The interaction between dopamine and the redox active cerium oxide nanoparticles,
      or nanoceria was studied using a suite of spectroscopic and surface
      characterization methods. Changes in the chemical reactivity and concentration of
      dopamine upon exposure to nanoceria was assessed in aqueous solutions and a human
      physiological fluid--human serum. The results indicate strong attachment of
      dopamine to the nanoparticle surface through oxidation followed by chemisorption
      of the oxidative product with formation of a charge transfer complex. Such
      oxidation/surface adsorption processes between nanoceria and dopamine lead to a
      reduction of the concentration of free dopamine in aqueous environments. These
      findings suggest that the redox reactivity of nanoceria may alter dopamine levels
      in biological systems exposed to these particles and indicate the need for a
      comprehensive assessment of the potential neurological consequences that might
      result from intended or unintended exposure to these particles.

PMID- 24461842
TI  - Mineral surface charge development in mixed electrolyte solutions.
AB  - Effects of competing counterions with different charge-to-size ratios on
      potential-determining ion (pdi; H(+), OH(-)) adsorption at mineral/water
      interfaces were resolved in mixtures of aqueous solutions of NaCl and NaClO4
      solutions. These effects were monitored on two synthetic goethite (alpha-FeOOH)
      particle preparations with distinct charge uptake capacities arising from
      differences in surface roughness. Charge development at these mineral surfaces
      was chiefly explored by high precision potentiometric titrations at 25  degrees
      C. These measurements confirmed that the greater charge-to-size ratio chloride
      ion not only promoted greater surface charge, but also had pronounced effects in
      perchlorate-dominated solutions. Cryogenic X-ray photoelectron spectroscopic
      measurements confirmed that perchlorate retains significant loadings at the
      goethite surface, even in the presence of chloride. Molecular dynamics
      simulations of the (110) plane of goethite exposed to these mixed solutions
      showed that chloride compressed the interfacial region containing electrolyte
      ions. Perchlorate, on the other hand, is not only present over a thicker region
      of the interface but also promotes an additional outer-sphere sodium species.
      These findings were used to develop a thermodynamic adsorption model predicting
      charge development at these mineral surfaces. The model involves a new
      formulation accounting for coexisting ion-specific regions each with their
      distinct compact plane capacitance values. The model can predict charge
      development in any mixtures of NaCl and NaClO4 contacted with goethite particles
      of contrasting charge uptake capacities without any additional parameters. This
      model can also be applied to a broader range of material surfaces.

PMID- 24461843
TI  - Comparison of aluminum modified natural materials in the removal of fluoride
      ions.
AB  - The removal behaviors of fluoride ions from aqueous solutions and drinking water
      by aluminum modified hematite, zeolitic tuff and calcite were determined.
      Drinking water containing naturally 8.29 mg of fluoride ions per liter was
      characterized. The hematite, zeolitic tuff and calcite were aluminum modified by
      an electrochemical method. The effects of contact time and the dose of adsorbent
      were determined. The PZC (point of zero charge) values for aluminum modified
      hematite, zeolitic tuff and calcite were 6.2, 5.8 and 8.4, respectively.
      Adsorption kinetic data were best fitted to pseudo-second-order and Elovich
      models and equilibrium data to Langmuir-Freundlich isotherm model. The highest
      fluoride sorption capacities (10.25 and 1.16 mg/g for aqueous solutions and
      drinking water respectively) were obtained for aluminum modified zeolite with an
      adsorbent dosage of 10 g/L and an initial F(-) concentration of 9 and 8.29 mg/L
      for aqueous solutions and drinking water respectively (the final concentrations
      were 0.08 and 0.7 mg/L respectively). The main mechanism involved in the
      adsorption of fluoride ions is chemisorption on heterogeneous materials according
      to the results obtained by fitting the data to kinetic and isotherm models
      respectively. Aluminum modified zeolitic tuff showed the best characteristics for
      the removal of fluoride ions from water.

PMID- 24461845
TI  - Enhanced electrochemical performance of ammonium vanadium bronze through sodium
      cation intercalation and optimization of electrolyte.
AB  - A new type of platelet-like ammonium vanadium bronze (NH4)2V6O16 is first used as
      cathode material for Na-ion battery. The discharge capacity and cycling stability
      is improved by the intercalation of Na(+) and using NaPF6 as electrolyte. Raman
      spectrum shows that the crystalline structure of (NH4)2V6O16 is changed after the
      intercalation of Na(+) to (NH4)2V6O16. Furthermore, the obtained sodium ammonium
      vanadium bronze shows smaller charge transfer resistance than (NH4)2V6O16, which
      would favor superior discharge capacity and good cycling stability. Additionally,
      NaPF6 is prior to NaClO4 as electrolyte for ammonium vanadium bronze cathode
      materials. 

PMID- 24461844
TI  - The effect of oil type on the aggregation stability of nanostructured lipid
      carriers.
AB  - Second generation lipid systems for the delivery of bioactive compounds have been
      developed by mixing a liquid carrier oil with a solid lipid to form so-called
      nanostructured lipid carriers (NLCs). In this study, we investigated the effect
      of different liquid carrier oils on the crystallization and aggregation behavior
      of tristearin NLC dispersions. We found that NLC suspension stability was
      strongly affected by the type and amount of the carrier oil. As the oil
      concentration was increased, the crystallization and melting temperatures
      decreased, the polymorphic transformation rate increased, the particles became
      more spherical, and suspension stability was enhanced. These results suggest that
      oil trapped within the growing crystal matrix accelerated polymorphic
      transformation but retarded the large shape change normally associated with the
      transformation. We also found that considerably less surfactant was necessary to
      produce stable NLC suspensions than was required to stabilize solid lipid
      nanoparticle (SLN) suspensions without a carrier oil. Based on preliminary
      simulation results, we hypothesized that improved NLC suspension stability was
      attributable to both reduced particle shape change, which created less new
      surface area to be covered by surfactant, and increased mobility of surfactant
      molecules, which resulted in available surfactant being more efficient at
      covering created surface area. 

PMID- 24461846
TI  - Arrays of ZnO/AZO (Al-doped ZnO) nanocables: a higher open circuit voltage and
      remarkable improvement of efficiency for CdS-sensitized solar cells.
AB  - Photoelectrode of nanocables (NCs) structure of ZnO nanowires (NWs) coated with
      Al-doped ZnO (AZO) shells was investigated for CdS quantum dots sensitized solar
      cells (QDSSCs). ZnO NWs serve as the frame for the preparation of AZO shells, in
      which electron transport more rapidly due to the more higher electron mobility of
      AZO (n-ZnO) than that of i-ZnO. AZO shells were assembled onto the surface of ZnO
      NWs via a spin-coating method. Optical band-gap of the ZnO/AZO films varies from
      3.19 eV for pure ZnO to 3.25 eV for AZO (15%) depending on the Al-doping
      concentration. The PL intensity of AZO/ZnO, V(oc), J(sc) and eta of the cells
      first increased and then decreased with the increase in the Al-doping (from 0% to
      20%) and post-annealed temperature. Remarkably, the value of V(oc) can achieve
      above 0.8 V after Al-doping. The dark current and absorption spectrum provided
      direct evidence of the increase in J(sc) and V(oc), respectively. Moreover, we
      discussed the effect of Al-doping on optical band-gap of the samples and the
      transfer of electron.

PMID- 24461847
TI  - Experimental investigation of the effects of ionic micelles on colloidal
      stability.
AB  - The effects of ionic micelles (tetradecyltrimethylammonium bromide (C14TAB) and
      sodium dodecylsulfate (SDS)) on the stability of a dispersion of highly charged
      silica particles was investigated both visually and using UV-vis absorption. As
      the surfactant concentration increased from 0 to 30 cmc, a clear critical
      flocculation concentration was observed with both surfactants. For SDS,
      restabilization was observed at 20 cmc. These stability results were compared to
      energy profiles that were calculated using measured force profiles between a
      single silica sphere and plate obtained with colloid-probe atomic force
      microscopy. It was found that flocculation would occur once the energy well
      formed by depletion attraction exceeded 3 k(B)T, while restabilization occurred
      once the long range structural energy barrier exceeded 8 k(B)T. These values are
      consistent with the energy levels needed for flocculation and restabilization
      predicted by other researchers.

PMID- 24461848
TI  - Formation of liquid sheets by deposition of droplets on a surface.
AB  - Experiments were done to observe the coalescence of highly viscous liquid
      droplets (87 wt% glycerin-in-water solutions) deposited onto a flat, solid steel
      plate. Droplets were deposited sequentially in straight lines or square droplet
      arrays. Droplet center-to-center distance was varied and the final dimensions of
      lines and sheets measured from photographs. When overlapping droplets were
      deposited surface tension forces pulled impacting droplets towards those already
      on the surface, a phenomena known as drawback. A dimensionless drawback index,
      quantifying the extent of droplet displacement, was calculated from experimental
      measurements for different values of droplet overlap. At large overlaps droplets
      deposited in a line or square array coalesced to form a circular film. When the
      droplet center-to-center distance increased, leading to less interaction, long,
      thin lines and square sheets were formed. As overlap was further decreased lines
      and sheets became discontinuous. A simple model was developed to predict the
      conditions under which rupture occurred. The lowest droplet overlap ratio
      (defined as droplet overlap distance divided by droplet spread diameter) at which
      a continuous liquid film could be formed was lambda=0.293. At large overlap
      ratios (lambda>0.6) droplets deposited in a square array formed a circular film.
      The minimum thickness of a continuous film formed by coalescence of droplets was
      shown to vary from 5% to 70% of the initial droplet diameter while increasing
      impact Weber and Reynolds number reduced the film thickness.

PMID- 24461849
TI  - Rational evaluation of the utilization of PEG-PEI copolymers for the facilitation
      of silica nanoparticulate systems in biomedical applications.
AB  - HYPOTHESIS: Polymer constructs are often applied in nanoparticulate systems to
      expand their applicability. One such common macromolecular modifier is
      poly(ethylene imine) - poly(ethylene glycol) copolymers. Despite their quite
      widespread use, and considering that interaction and stabilization mechanisms
      when combining a polyelectrolyte with a non-charged polymer are not trivial to
      pinpoint, these systems are generally poorly characterized in literature. Here,
      we attempt to provide a solid rationale to utilize PEG-PEI copolymers as surface
      modifiers and stabilizers/dispersion agents in solid colloidal systems with focus
      on biomedical applicability. EXPERIMENTAL: mPEG grafted PEI copolymers with two
      different grafting densities and 100 nm sized non-porous silica nanoparticles
      (SiNP) were synthesized. Detailed physico-chemical characterization of all
      prepared materials was conducted with spectroscopic methods, while the
      interaction mechanisms between the produced copolymers and SiNP were investigated
      by calorimetry. The influence of increased PEG grafting ratio on the attained
      colloidal stability of copolymer functionalized SiNP was studied by multiple
      light scattering, and its further implications on the biobehavior of SiNP were
      evaluated. FINDINGS: The interaction mechanism between SiNP and copolymers was
      concluded to be mainly directed by electrostatics, whereas an influence of PEG
      grafting density on the adsorption process was also observed. The implications of
      the surface modifications on the in vitro biobehavior of SiNP were investigated
      by combining the knowledge obtained by the detailed characterizations with
      microscopy evaluation under in vitro conditions.

PMID- 24461850
TI  - Microwave-assisted modification on montmorillonite with ester-containing Gemini
      surfactant and its adsorption behavior for triclosan.
AB  - To obtain effective adsorbent that can remove emerging organic pollutant of
      triclosan (TCS) in aquatic environment, different ester-containing Gemini
      surfactant-modified MMT (EMMT) were prepared under microwave irradiation. The
      whole process was rapid, uniform, easy and energy-efficient. The structures and
      morphology of EMMT were characterized by XRD, TEM, FT-IR, SEM and TGA. The
      results revealed that the saturated intercalation amount of this surfactant was
      0.8 times to cation exchange capacity (CEC) of MMT, and there was electrostatic
      interaction between ester-containing Gemini surfactant and MMT. In addition, they
      bound in the ways of intercalation, intercalation-adsorption or adsorption, which
      relied on the dosage of the surfactant. The surface of EMMT was hydrophobic,
      rough and fluffy, which contributed to its strong adsorption capacity. The
      adsorption equilibrium data of EMMT for TCS were fitted to Langmuir and
      Freundlich isothermal adsorption model. The result showed that Langmuir
      isothermal adsorption model could describe the adsorption behavior better, the
      adsorption behavior of TCS on EMMT was confirmed to a surface monolayer
      adsorption, and notably the theoretical maximum adsorption capacity was up to 133
      mg/g. Therefore, this work lays important foundation on developing effective and
      safe absorbent materials for the treatment of emerging organic pollutants.

PMID- 24461851
TI  - Growth of BiOBr nanosheets on C3N4 nanosheets to construct two-dimensional
      nanojunctions with enhanced photoreactivity for NO removal.
AB  - The development of approaches to effectively separate the photo-induced charge
      carriers is a key strategy to promote the photocatalytic activity of
      semiconductor photocatalysts. This work represents the construction of novel two
      dimensional (2D) BiOBr/C3N4 nanojunctions by the growth of BiOBr nanosheets on
      the surface of C3N4 nanosheets at room temperature. The samples were
      characterized by XRD, FT-IR, TEM, UV-vis DRS and PL. The photocatalytic activity
      of the samples was evaluated by the removal of NO in air under visible light
      irradiation. The results indicated that electronic coupling took place between
      the {001} plane of BiOBr and {002} plane of C3N4. The BiOBr/C3N4 nanojunctions
      exhibited enhanced visible light photocatalytic activity compared with pure BiOBr
      and C3N4. The enhanced photoactivity can be mainly ascribed to the efficient
      separation and transportation of photo-induced electrons and holes due to the
      well-coupled crystal planes and well-matched band structures. The present work
      could provide new insights into the design and construction of 2D nanojunctions
      with well-matched crystal planes and band structures for efficient visible light
      photocatalysis. 

PMID- 24461852
TI  - Interaction between dipeptide (glycyl-phenylalanine) and ninhydrin: role of CTAB
      and gemini (16-s-16, s=4, 5, 6) surfactant micelles.
AB  - The kinetics of interaction of dipeptide glycylphenylalanine (Gly-Phe) with
      ninhydrin have been studied by following the reaction spectrophotometrically at
      70  degrees C and a particular pH 5.0 in the absence and presence of conventional
      cetyltrimethylammonium bromide (CTAB) and gemini (alkanediyl-alpha,omega
      bis(dimethylhexadecylammonium bromide)) surfactants. The rate shows first- and
      fractional-order dependence on [Gly-Phe] and [ninhydrin], respectively. The
      surfactants were found to catalyse the reaction. Furthermore, whereas the typical
      rate constant (kPsi) increase and leveling-off regions are observed with geminis,
      just like as seen with conventional surfactants, the former produced a third
      region of increasing kPsi at higher concentrations. A kinetic rate law consistent
      with experimental results has been derived on the basis of the proposed
      mechanism.

PMID- 24461853
TI  - Fe/S doped granular activated carbon as a highly active heterogeneous persulfate
      catalyst toward the degradation of Orange G and diethyl phthalate.
AB  - Fe/S doped granular activated carbon (Fe/SGAC) was synthesized with ferric
      nitrate, Na2S2O3 and (NH4)2S2O8 via an impregnation-precipitation, reduction
      oxidation combining with aqueous-phase synthesis method treatment. Surface
      density of functional groups, surface area changes as well as the chemical state
      inside Fe/SGAC catalyst were studied by Boehm titration, N2 adsorption and X-ray
      photoelectron spectroscopy (XPS). The reactivity of the catalysts was tested by
      degrading Orange G (OG) and diethyl phthalate (DEP). The Fe/SGAC catalysts could
      significantly enhance the removal rate of OG as compared to persulfate alone and
      PS/GAC. And the catalytic capacity was also enhanced by S doping. But the
      degradation of DEP under the similar condition was inhibited by adsorption
      process because of the different hydrophobicities of OG and DEP molecule.
      Fe2O3/FeOOH (Fe(3+)) (represents ferrihydrite) together with FeO/Fe3O4 (Fe(2+))
      and Fe2O3-satellite, which provide the new active site for persulfate catalyst
      was found to be the major components of iron element in Fe/SGAC catalyst; the
      existence of FeS2(S(-)) for sulfur element verified the assumption that the doped
      S element promoted the electron transfer between the persulfate species and iron
      oxide at the interface. COD removal experiment further confirmed that mostly
      contaminant removal was owed to the Fe/SGAC catalytic persulfate oxidation
      process. 

PMID- 24461855
TI  - Synthesis of P(AM-co-MAA)/AEM composite microspheres with lichi-like surface
      structure using porous microgel as template.
AB  - The P(AM-co-MAA)/AEM composite microspheres with lichi-like structure were
      synthesized by the hydrolysis and condensation of 3-(trimethoxysilyl)
      propyldimethyloctadecyl-ammonium chloride (AEM) located within porous
      poly(acrylamide-co-methylacrylic acid) (P(AM-co-MAA)) microgels in an ammonia
      water atmosphere. The morphology and composition of the composite microspheres
      were characterized by scanning electron microscopy (SEM), thermogravimetric
      analysis (TGA), Fourier transform infrared spectrometer (FI-IR), and X-ray
      photoelectron spectroscopy (XPS), respectively. The results indicated that the
      composite microspheres with lichi-like surface structure could be obtained by
      controlling the loaded amount of AEM, the hydrolysis-condensation time of AEM,
      and the cross-linking degree of the porous P(AM-co-MAA) microgels. On the basis
      of the results, the mechanism on the formation of the microspheres with lichi
      like surface structure was proposed. The multiple factors play a role in the
      formation of the specific surface morphology. The pores of the porous microgels
      make AEM behavior localized; the migration of AEM along with solvent evaporation
      leads to the structural change; the hydrolysis-condensation of AEM brings the
      temporarily structural solidification; the surface tension of hydrophobic AEM in
      hydrophilic atmosphere induces AEM liquid membrane constriction. Although the
      mechanism is complicated, the method is very simple. Based on the analogous
      principle, other composite materials with lichi-like structure could be
      constructed by altering precursor and porous template. 

PMID- 24461854
TI  - Fabrication and structure of "polymer nanosphere multilayered organization".
AB  - We constructed a multiparticle layered organization of aromatic polyamides with
      rigid main chains and flexible side chains by the Langmuir-Blodgett (LB)
      technique, which resulted in a highly regular arrangement along the c-axis. The
      particle arrangement was estimated by performing out-of-plane X-ray diffraction
      (XRD) analysis and atomic force microscopic (AFM) observation. The results
      suggest that a double-particle layered structure (Y-type) is formed by the LB
      technique, forming amphiphilic particles at the air/water interface. Copolymers
      with highly hydrophobic carbazole contents and both hydrogenated and fluorinated
      side-chains also formed a single-particle layer at the air/water interface and
      exhibited multiparticle layers by a LB technique. Therefore, it is possible to
      control the formation of single- and double-particle layered structure using
      these techniques. Further, it was found that multiparticle layered organization
      of polymer nanospheres and polymer nanosheets could be formed simultaneously with
      the same component material. 

PMID- 24461856
TI  - Facile preparation of SERS-active nanostructured Au spheres by simple reduction
      of AuCl4- ions with EDOT.
AB  - Uniform submicron-scale Au spheres with an average dimension of 574 nm were
      facilely prepared from the redox reaction between HAuCl4 and 3,4
      ethylenedioxythiophene (EDOT) in aqueous solution under ambient conditions.
      HAuCl4 precursor readily polymerized to poly(3,4-ethylenedioxythiophene) (PEDOT)
      and metallic Au spheres simultaneously formed within a short period of time. The
      Au spheres are consisted of two slightly different types of spherical particles
      based on their surface textures. Major raspberry-like Au spheres are formed
      through the assembly of very tiny Au nanoparticles, while minor rosette-like Au
      spheres are formed through the dense packing of Au nanoplates. Both Au spheres
      are pure metallic face-centered cubic Au based on X-ray photoelectron
      spectroscopy and powder X-ray diffraction. The resultant Au spheres are adequate
      for application to surface-enhanced Raman scattering (SERS) due to their rough
      surfaces and nanogaps on the surfaces. Both methylene blue and crystal violet
      molecules were detectable at concentrations as low as 10(-7) M.

PMID- 24461857
TI  - Poly (vinylsulfonic acid) assisted synthesis of aqueous solution stable vaterite
      calcium carbonate nanoparticles.
AB  - Calcium carbonate nanoparticles of the vaterite polymorph were synthesized by
      combining CaCl2 and Na2CO3 in the presence of poly (vinylsulfonic acid) (PVSA).
      By studying the important experimental parameters we found that controlling PVSA
      concentration, reaction temperature, and order of reagent addition the particle
      size, monodispersity, and surface charge can be controlled. By increasing PVSA
      concentration or by decreasing temperature CCNPs with an average size from ~150
      to 500 nm could be produced. We believe the incorporation of PVSA into the
      reaction plays a dual role to (1) slow down the nucleation rate by sequestering
      calcium and to (2) stabilize the resulting CCNPs as the vaterite polymorph,
      preventing surface calcification or aggregation into microparticles. The obtained
      vaterite nanoparticles were found to maintain their crystal structure and surface
      charge after storage in aqueous buffer for at least 5 months. The aqueous stable
      vaterite nanoparticles could be a useful platform for the encapsulation of a
      large variety of biomolecules for drug delivery or as a sacrificial template
      toward capsule formation for biosensor applications.

PMID- 24461858
TI  - Temperature effects on dynamic water absorption into paper.
AB  - Mechanisms controlling short time water absorption and the effect of temperature
      on water absorption into paper were investigated by analyzing previously
      published data. A dynamic contact angle effect caused by contact line friction
      explained the liquid uptake dynamics at short times. The water absorption rate
      increase with temperature is suggested to be controlled by the molecular
      processes occurring in front of the advancing liquid front. The increase in the
      non-equilibrium vapor pressure at air-liquid interface leads to higher water
      molecule adsorption onto fibers and associated lowering of the solid-gas
      interfacial tension, thereby increasing the wetting velocity and water
      absorption. The classical Lucas-Washburn equation was found to be inadequate for
      predicting water absorption into paper both at short times and as a function of
      temperature. 

PMID- 24461860
TI  - Discussion.

PMID- 24461859
TI  - The current management of isolated degenerative femoral artery aneurysms is too
      aggressive for their natural history.
AB  - BACKGROUND: Previous studies have combined anastomotic, catheter-induced, and
      atherosclerotic isolated femoral artery aneurysms (FAAs) to achieve adequate
      numbers for analysis and have recommended repair of asymptomatic FAAs with
      diameters >=2.5 cm and all symptomatic FAAs. This study evaluated the
      contemporary management of isolated FAAs. METHODS: Patients with FAAs were
      evaluated using a standardized, prospectively maintained database by a research
      consortium. RESULTS: From 2002 to 2012, 236 FAAs were identified in 182 patients
      (mean age, 72 years; male-to-female ratio, 16:1) at eight institutions. The mean
      nonoperative mean diameter was 2.8 +/- 0.7 cm, and the operative diameter was 3.3
      +/- 1.5 cm. FAA location was the common femoral artery in 191, superficial
      femoral artery (SFA) in 34, and profunda femoris artery in 11. Synchronous
      aneurysms (mean, 1.7 per patient) occurred in the aorta (n = 113), in the iliac
      (n = 109), popliteal (n = 86), and hypogastric (n = 56) arteries, and in the
      contralateral common femoral artery (n = 34), SFA (n = 9), and profunda femoris
      artery (n = 2). Of the aneurysms repaired, 66% were asymptomatic; other
      indications for repair were claudication (18%), local pain (8%), nerve
      compression (3%), rupture (2%), acute thrombosis (1%), and rest pain (0.5%).
      Acute aneurysm-related complications (rupture, thrombosis, embolus) were
      associated (P < .05) with FAA diameter >4 cm and intraluminal thrombus, but not
      location. Mean diameter of asymptomatic aneurysms that developed acute
      complications was 5.7 +/- 1.3 cm for rupture, 4 +/- 1.1 cm for thrombosis, and
      3.5 cm for embolus. Repair was by interposition or bypass graft in 177 FAAs and
      by endovascular repair in three SFA aneurysms. Two perioperative deaths, of
      myocardial infarction and multisystem organ failure, occurred at 30 days.
      Operative complications included wound infection (6%), seroma (3%), and bleeding
      (2%). No amputations occurred through 5 years in the operative or nonoperative
      groups. Survival in operated-on patients was 99% (n = 138) at 3 months, 92% at 1
      year, and 81% (n = 20) at 5 years. CONCLUSIONS: This largest study of isolated
      FAAs demonstrates that (1) acute complications did not occur in FAAs <=3.5 cm,
      repair criteria of asymptomatic FAAs should be changed to >3.5 cm, and chronic
      intraluminal thrombus should reduce the threshold for repair, and that (2)
      current indications for symptomatic FAA repair result in low morbidity and should
      remain unchanged.

PMID- 24461861
TI  - Clinical significance of embolic events in patients undergoing endovascular
      femoropopliteal interventions with or without embolic protection devices.
AB  - OBJECTIVE: The purpose of this study was to evaluate the incidence and clinical
      significance of embolic events in patients undergoing endovascular
      femoropopliteal interventions with or without embolic protection devices (EPDs).
      METHODS: We reviewed the clinical data of 566 patients treated by 836
      endovascular femoropopliteal interventions for lower extremity claudication (46%)
      or critical limb ischemia (54%) from 2002 to 2012. Outcomes were analyzed in 74
      patients/87 interventions performed with EPDs (Spider Rx; Covidien, Plymouth,
      Minn) and 513 patients/749 interventions performed without EPDs. TransAtlantic
      Inter-Society Consensus (TASC) II classification, runoff scores, and embolic
      events were analyzed. End points were morbidity, mortality, reintervention,
      patency, and major amputation rates. RESULTS: Both groups had similar
      demographics, indications, cardiovascular risk factors, and runoff scores, but
      patients treated with EPDs had significantly (P < .05) longer lesions (109 +/- 94
      mm vs 85 +/- 76 mm) and more often had occlusions (64% vs 30%) and TASC C/D
      lesions (56% vs 30%). Embolic events occurred in 35 of 836 interventions (4%),
      including two (2%) performed with EPD and 33 (4%) without EPD (P = .35).
      Macroscopic debris was noted in 59 (68%) filter baskets. Embolic events were not
      associated with lesion length, TASC classification, runoff scores, treatment
      type, or indication but were independently associated with occlusion. Patients
      who had embolization required more reinterventions (20% vs 3%; P < .001) and
      major amputations at 30 days (11% vs 3%; P = .02). There was no difference in
      hospital stay (2.4 +/- 4 days vs 1.6 +/- 2 days; P = .08), reintervention (2% vs
      4%), and major amputation (1% vs 4%) among patients treated with or without EPD,
      respectively. The two patients who developed embolization with EPDs had no
      clinical sequela and required no reintervention. Most emboli were successfully
      treated by catheter aspiration or thrombolysis, but eight patients (24%) treated
      without EPD required prolonged hospital stay, seven (21%) had multiple
      reinterventions, one (3%) had unanticipated major amputation, and one (3%) died
      from hemorrhagic complications of thrombolysis. Median follow-up was 20 months.
      At 2 years, primary patency and freedom from reintervention was similar for TASC
      A/B and TASC C/D lesions treated with or without EPDs. CONCLUSIONS: Rates of
      embolization are low in patients undergoing endovascular femoropopliteal
      interventions with (4%) or without (2%) EPD. Embolization is more frequent in
      patients with occlusions. While emboli in patients with EPD had no clinical
      sequel, those treated without EPD required multiple reinterventions in 21% or
      resulted in major amputation or death in 3%. Late outcomes were similar in
      patients treated with or without EPDs.

PMID- 24461862
TI  - Primary stenting of femoropopliteal atherosclerotic lesions using new helical
      interwoven nitinol stents.
AB  - BACKGROUND: The Supera helical interwoven nitinol stent has enhanced flexibility
      in counteracting fractures when placed in the femoropopliteal arteries and may
      improve patency. The aim of this study is to assess the early results of the
      Supera stent in symptomatic patients with femoropopliteal atherosclerotic
      lesions. METHODS: From October 2011 to April 2013, patients with symptomatic
      femoropopliteal lesions were treated with angioplasty and primary stenting using
      the Supera stent. They were followed up at 1, 3, 6, and 12 months with clinical,
      duplex, and radiographic assessments. Failure was defined as >50% restenosis of
      the target lesion on duplex ultrasound imaging or stent fracture on X rays.
      RESULTS: A total of 78 consecutive patients (46 males, 32 females) with 82 legs,
      mean age of 78.5 years (range, 57-97 years) were included. Symptoms of
      claudication, rest pain, and tissue loss were 48 (59%), 8 (10.1%), and 30 (37%),
      respectively. Ninety-six Supera stents were inserted in total. In 44 (53.7%) of
      the legs, stents were extended to the popliteal segments. The mean stented length
      was 12.6 cm (range, 4.0-38.0 cm). The primary patency rates at 6 and 12 months
      were 83.5% and 78.6%, respectively. The ankle brachial index increased from 0.58
      +/- 0.16 preoperative to 0.87 +/- 0.14 postoperative. There were no stent
      fractures. Patency rate was not affected by severity of symptoms, stent lengths,
      femoro/popliteal stents (log-rank test, P = .50, .13, .52). All the patients
      reported symptomatic improvement. There was no procedural- or device-related
      morbidity or mortality, no major amputation after revascularization, and 10
      patients died of unrelated cardiopulmonary/renal causes on follow-up.
      CONCLUSIONS: Our early experience shows that the Supera stents are effective in
      our cohort of elderly patients, with acceptable patency rates. There were no
      stent fractures so far even with stenting of the popliteal segments.

PMID- 24461863
TI  - Determinants of invasive treatment in lower extremity peripheral arterial
      disease.
AB  - OBJECTIVE: Since it is unknown what factors are weighed in a clinician's decision
      to refer patients with symptomatic lower extremity peripheral arterial disease
      (PAD) for invasive treatment, we examined the relationship between health status,
      lesion location, and site variations and invasive treatment referral <=1 year
      following diagnosis in patients with PAD. METHODS: This was a prospective
      observational cohort study on ambulatory patients that presented themselves at
      two vascular surgery outpatient clinics. A total of 970 patients with new
      symptoms of PAD or with an exacerbation of existing PAD symptoms that required
      clinical evaluation and treatment (Rutherford Grade I) were eligible, 884
      consented and were included between March 2006 and November 2010. We report on
      505 patients in the current study. Prior to patients' initial PAD evaluation, the
      Short Form-12, Physical Component Scale (PCS) was administered to measure health
      status. Anatomical lesion location (proximal vs distal) was derived from duplex
      ultrasounds. PCS scores, lesion location, and site were evaluated as determinants
      of receiving invasive (endovascular, surgery) vs noninvasive treatment <=1 year
      following diagnosis in Poisson regression analyses, adjusting for demographics,
      ankle-brachial index, and risk factors. RESULTS: Invasive treatment as a first
      choice was offered to 167 (33%) patients. While an association between poorer
      health status and invasive therapy was found in unadjusted analyses (relative
      risk [RR], 0.98; 95% confidence interval [CI], 0.97-1.00; P = .011), proximal
      lesion location (RR, 3.66; 95% CI, 2.70-4.96; P < .0001) and site (RR, 1.69; 95%
      CI, 1.11-2.58; P = .014) were independent predictors of invasive treatment
      referral in the final model. CONCLUSIONS: One-third of patients were treated
      invasively following PAD diagnosis. Patients' health status was considered in
      providers' decision to refer patients for invasive treatment, but having a
      proximal lesion was the strongest predictor. This study also found some important
      first indications of site variations in offering invasive treatment among
      patients with PAD. Future work is needed to further document these variations in
      care.

PMID- 24461865
TI  - Hybrid repair of ruptured thoracoabdominal aortic aneurysm in a patient with
      previous endovascular abdominal aortic aneurysm repair and thoracic endovascular
      aneurysm repair.

PMID- 24461866
TI  - Cavernous hemangioma of the external carotid artery.

PMID- 24461867
TI  - Preserved distal flow in a proximally occluded internal carotid artery due to a
      persistent proatlantal artery.

PMID- 24461869
TI  - Publishing corruption discussion: predatory journalism.
AB  - Dr Spock is a brilliant young vascular surgeon who is up for tenure next year. He
      has been warned by the chair of surgery that he needs to increase his list of
      publications to assure passage. He has recently had a paper reviewed by one of
      the top journals in his specialty, Journal X-special, with several suggestions
      for revision. He received an e-mail request for manuscript submission from a
      newly minted, open access, Journal of Vascular Disease Therapy, which promises a
      quick and likely favorable response for a fee. What should be done? A. Send the
      paper to another peer reviewed journal with the suggested revisions. B. Resubmit
      the paper to Journal X-special. C. Submit to the online journal as is to save
      time. D. Submit to the online journal and another regular journal. E. Look for
      another job.

PMID- 24461868
TI  - A systematic review and meta-analysis of the association between markers of
      hemostasis and abdominal aortic aneurysm presence and size.
AB  - OBJECTIVE: The purpose of this study was to summarize the current evidence of the
      association between markers of hemostasis and both the presence and size of
      abdominal aortic aneurysms (AAAs). METHODS: A systematic review and meta-analysis
      was performed according to Preferred Reporting Items for Systematic reviews and
      Meta-Analyses guidelines by use of the search terms "aneurysm AND abdominal AND
      aortic AND coagulation" NOT "thoracic." Outcome data including concentration of
      hemostatic marker, number of patients, and significance level were recorded.
      RESULTS: A total of 22 nonrandomized studies were included in the analysis, with
      a total of 9862 patients. Fibrinogen mean difference (MD) (0.43 g/L; 95%
      confidence interval [CI], 0.28-0.58 g/L; P <= .00001), D-dimer MD (325.82 ng/mL;
      95% CI, 199.74-451.89 ng/mL; P <= .00001), and thrombin-antithrombin III complex
      MD (5.58 g/L; 95% CI, 3.34-7.83 g/L; P <= .0001) were significantly elevated in
      the presence of AAAs. Tissue plasminogen activator, prothrombin fragments F1+F2,
      and platelet count were not shown to be significantly different between patients
      with and those without AAAs. Meta-regression of studies reporting plasma D-dimer
      concentration and aneurysm diameter suggests a strong and significant association
      (r(2) = 0.94; P <= .0001). CONCLUSIONS: This study suggests that the presence of
      AAAs is associated with increased fibrin turnover, fibrinolysis, and thrombin
      generation, as shown by increased levels of fibrinogen, D-dimer, and thrombin
      antithrombin III complex. This is clinically relevant because markers of
      hemostasis are independent risk factors for cardiovascular events, highlighting
      the necessity of addressing all modifiable cardiovascular risk factors in
      patients with AAAs. Furthermore, the finding that plasma D-dimer concentration
      appears to have a linear relationship with aneurysm diameter may be useful as a
      future biomarker of AAAs.

PMID- 24461870
TI  - Endovascular-first approach is not associated with worse amputation-free survival
      in appropriately selected patients with critical limb ischemia.

PMID- 24461871
TI  - Regarding "Cerebral hemodynamic benefits after carotid artery stenting in
      patients with near occlusion".

PMID- 24461872
TI  - Regarding "Thoracic endovascular aneurysm repair, race, and volume in thoracic
      aneurysm repair".

PMID- 24461873
TI  - Reply: To PMID 23891492.

PMID- 24461874
TI  - Reply: To PMID 23182647.

PMID- 24461876
TI  - Administering 25-hydroxyvitamin D3 in vitamin D-deficient young type 1A diabetic
      patients reduces reactivity against islet autoantigens.
AB  - BACKGROUND & AIMS: We investigated whether improving 25-hydroxyvitamin D status
      in young type 1A diabetic patients reduces reactivity of peripheral blood
      mononuclear cells against islet autoantigens and associates with beta-cell
      functional changes. METHODS: Eight patients with 25-hydroxyvitamin D deficiency
      (<20 ng/ml), out of 15 consecutive young type 1A diabetic subjects received 25
      hydroxyvitamin D3 to achieve and maintain levels above 50 ng/ml for up to one
      year. Peripheral blood mononuclear cell reactivity (Interferon-gamma spots)
      against beta-cell autoantigens (glutamic acid decarboxylase 65-kD isoform,
      proinsulin and tyrosine phosphatase-like protein IA-2) and C-peptide during mixed
      meal were assessed before and after 25-hydroxyvitamin D3 replenishment. RESULTS:
      Target 25-hydroxyvitamin D blood levels were safely reached and maintained.
      Peripheral blood mononuclear cell reactivity against glutamic acid decarboxylase
      65-kD isoform (3.8 +/- 4.0 vs. 45 +/- 16) and proinsulin (3.5 +/- 3.2 vs. 75 +/-
      51) decreased significantly (p < 0.001 and p < 0.02) upon 25-hydroxyvitamin D3
      replenishment, which was correlated with 25-hydroxyvitamin D concentrations. C
      peptide values remained stable after one year of treatment. CONCLUSIONS: Safely
      restored and maintained 25-hydroxyvitamin D levels associated with reduced
      peripheral blood mononuclear cell reactivity against beta-cell autoantigens with
      no significant decrease of beta-cell function in this cohort of patients.

PMID- 24461877
TI  - Adaptive regulation of amino acid metabolism on early parenteral lipid and high
      dose amino acid administration in VLBW infants - a randomized, controlled trial.
AB  - BACKGROUND & AIMS: An anabolic state can be achieved upon intravenous amino acid
      administration during the immediate postnatal phase despite a low energy intake.
      The optimal dosing of amino acid and energy intake has yet to be established. The
      aim was to quantify the efficacy of early initiation of parenteral lipids and
      increased amounts of amino acids on metabolism and protein accretion in very low
      birth weight infants. METHODS: 28 very low birth weight infants were randomized
      to receive parenteral nutrition with glucose and either 2.4 g amino acids/(kg.d)
      (control group), 2.4 g amino acids/(kg.d) plus 2-3 g lipid/(kg.d) (AA + lipid
      group), or 3.6 g amino acids/(kg.d) plus 2-3 g lipid/(kg.d) (high AA + lipid
      group) from birth onward. On postnatal day 2, we performed a stable isotope study
      with [1-(13)C]phenylalanine, [ring-D4]tyrosine, [U-(13)C6,(15)N]leucine, and
      [methyl-D3]alpha-ketoisocaproic acid to quantify intermediate amino acid
      metabolism. RESULTS: The addition of lipids only had no effect on phenylalanine
      metabolism, whereas the addition of both lipids and additional amino acids
      increased the amount of phenylalanine used for protein synthesis. In addition,
      high amino acid intake significantly increased the rate of hydroxylation of
      phenylalanine to tyrosine, increasing the availability of tyrosine for protein
      synthesis. However, it also increased urea concentrations. Increasing energy
      intake from 40 to 60 kcal/(kg.d) did not increase protein efficiency as measured
      by phenylalanine kinetics. The leucine data were difficult to interpret due to
      the wide range of results and inconsistency in the data between the phenylalanine
      and leucine models. CONCLUSIONS: High amino acid and energy intakes from birth
      onwards result in a more anabolic state in very low birth weight infants, but at
      the expense of higher urea concentrations, which reflects a higher amino acid
      oxidation. Long-term outcome data should reveal whether this policy deserves
      routine implementation. This trial was registered at www.trialregister.nl, trial
      number NTR1445, name Nutritional Intervention for Preterm Infants-2.

PMID- 24461878
TI  - Hospital-based school for children with chronic illness in Taiwan.
AB  - BACKGROUND/PURPOSE: To provide educational support and avoid unwanted damage that
      may impede learning for children with chronic illness, the learning environment
      should be friendly and safe. There is a need to establish schools inside
      hospitals, however, which may be neglected in a highly efficient health care
      system. A study was conducted to identify hospital-based schools for sick
      children in Taiwan, and to explore the barriers for implementation. METHODS: The
      data were collected by structured telephone interview and retrieval of hospital
      web information. The study targeted social workers and nurses in the pediatric
      wards of 29 hospitals, plus officials from the Education Bureau in Taiwan. The
      interviewers inquired about the availability of a formal educational program
      inside hospitals and the barriers (if any) in providing educational supports.
      RESULTS: Taiwan has only one hospital-based informal school and eight hospitals
      with rotating bedside teachers. Education inside hospitals occurs mostly through
      voluntary teaching in informal education models. Information about special
      educational resources has not been widely distributed to patients and health care
      providers. Professional personnel in Taiwan are not well aware of the needs to
      establish a hospital-based school. CONCLUSION: The educational needs of children
      with chronic illness can be easily neglected even in an industrialized country.
      The establishment of policy and the enrichment of professional education on
      advocacy are necessary to eliminate educational inequities and benefit sick
      children.

PMID- 24461875
TI  - Opening paths to novel analgesics: the role of potassium channels in chronic
      pain.
AB  - Chronic pain is associated with abnormal excitability of the somatosensory system
      and remains poorly treated in the clinic. Potassium (K+) channels are crucial
      determinants of neuronal activity throughout the nervous system. Opening of these
      channels facilitates a hyperpolarizing K+ efflux across the plasma membrane that
      counteracts inward ion conductance and therefore limits neuronal excitability.
      Accumulating research has highlighted a prominent involvement of K+ channels in
      nociceptive processing, particularly in determining peripheral hyperexcitability.
      We review salient findings from expression, pharmacological, and genetic studies
      that have untangled a hitherto undervalued contribution of K+ channels in
      maladaptive pain signaling. These emerging data provide a framework to explain
      enigmatic pain syndromes and to design novel pharmacological treatments for these
      debilitating states.

PMID- 24461879
TI  - E-cigarettes-too fast, too young?

PMID- 24461880
TI  - Postinfectious cough and pertussis in primary care.

PMID- 24461881
TI  - Pharmacogenetics of COPD: a role for the beta2-adrenergic receptor gene?

PMID- 24461882
TI  - The rise and fall of COPD mortality.

PMID- 24461883
TI  - New treatments for COPD: many miles still to go.

PMID- 24461884
TI  - Air pollution and health.

PMID- 24461885
TI  - Asthma heterogeneity and severity-why is comprehensive phenotyping important?

PMID- 24461886
TI  - Bronchiectasis: the arrival of better evidence.

PMID- 24461887
TI  - COPD drugs: the urgent need for innovation.

PMID- 24461888
TI  - Early feeding during critical illness.

PMID- 24461889
TI  - Idiopathic pulmonary fibrosis: on the move.

PMID- 24461890
TI  - Progress in research on screening and genetics in lung cancer.

PMID- 24461892
TI  - Emerging respiratory viral infections: MERS-CoV and influenza.

PMID- 24461891
TI  - Changing perceptions in pulmonary hypertension.

PMID- 24461893
TI  - Tuberculosis: progress and challenges in product development and delivery.

PMID- 24461894
TI  - Respiratory disease and fertility are linked-but why?

PMID- 24461895
TI  - The dream of making new lungs comes closer to fulfilment.

PMID- 24461896
TI  - Novel gene linked to severe childhood asthma.

PMID- 24461897
TI  - New cystic fibrosis genetic tests bring hope and dilemmas.

PMID- 24461898
TI  - Ambitious plans to improve respiratory health in Uganda.

PMID- 24461899
TI  - Patient, doctor, father, son.

PMID- 24461900
TI  - Montelukast for postinfectious cough in adults: a double-blind randomised placebo
      controlled trial.
AB  - BACKGROUND: Postinfectious cough is common in primary care, but has no proven
      effective treatments. Cysteinyl leukotrienes are involved in the pathogenesis of
      postinfectious cough and whooping cough (pertussis). We investigated the
      effectiveness of montelukast, a cysteinyl leukotriene receptor antagonist, in the
      treatment of postinfectious cough. METHODS: In this randomised, placebo
      controlled trial, non-smoking adults aged 16-49 years with postinfectious cough
      of 2-8 weeks' duration were recruited from 25 general practices in England.
      Patients were tested for pertussis (oral fluid anti-pertussis toxin IgG) and
      randomly assigned (1:1) to montelukast 10 mg daily or image-matched placebo for 2
      weeks. Patients chose whether to continue study drug for another 2 weeks. The
      randomisation sequence was computer-generated and stratified by general practice.
      Patients, health-care professionals, and researchers were masked to treatment
      allocation. Effectiveness was assessed with the Leicester Cough Questionnaire to
      measure changes in cough-specific quality of life; the primary outcomes were
      changes in total score between baseline and two follow-up stages (2 weeks and 4
      weeks). The primary analysis was by intention to treat with imputation by last
      observation carried forward. Recruitment closed on Sept 21, 2012, and follow-up
      has been completed. This trial is registered with EudraCT (2010-019647-19), UKCRN
      Portfolio (ID 8360), and ClinicalTrials.gov (NCT01279668). FINDINGS: From April
      13, 2011, to Sept 21, 2012, we randomly assigned 276 patients to montelukast
      (n=137) or placebo (n=139). 70 (25%) patients had laboratory-confirmed pertussis.
      Improvements in cough-specific quality of life occurred in both groups after 2
      weeks (montelukast: mean 2.7, 95% CI 2.2-3.3; placebo: 3.6, 2.9-4.3), but the
      difference between groups did not meet the minimum clinically important
      difference of 1.3 (mean difference -0.9, -1.7 to -0.04, p=0.04). This difference
      was not statistically significant in any sensitivity analyses. After 2 weeks, 192
      of 259 participants from whom data were available elected to continue study drug
      (99 [77%] of 129 participants on montelukast; 93 [72%] of 130 on placebo). After
      4 weeks, there were no significant between-group differences in cough-specific
      quality of life improvement (montelukast: 5.2, 4.5-5.9; placebo: 5.9, 5.1-6.7;
      mean difference -0.5, -1.5 to 0.6, p=0.38) or adverse event rates (21 (15%) of
      137 patients on montelukast reported one or more adverse events; 31 (22%) of 139
      on placebo; p=0.14). The most common adverse events reported were increased mucus
      production (montelukast, n=6; placebo, n=2), gastrointestinal disturbance
      (montelukast, n=3; placebo, n=5), and headache (montelukast, n=2; placebo, n=6).
      One serious adverse event was reported (placebo, n=1), which was unrelated to
      study drug (shortness of breath and throat tightness after severe coughing
      bouts). INTERPRETATION: Montelukast is not an effective treatment for
      postinfectious cough. However, the burden of postinfectious cough in primary care
      is high, making it an ideal setting for future antitussive treatment trials.
      FUNDING: National Institute for Health Research School for Primary Care Research,
      UK.

PMID- 24461901
TI  - Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in
      preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial.
AB  - BACKGROUND: The effect of beta2-adrenergic receptor (ADRB2) polymorphisms on the
      treatment response to longacting bronchodilators in chronic obstructive pulmonary
      disease (COPD) is unclear. We aimed to establish whether ADRB2 polymorphisms
      differentially affected COPD exacerbation outcomes in response to tiotropium
      versus salmeterol. METHODS: We did a prespecified analysis of the ADRB2
      polymorphisms Arg16Gly and Gln27Glu within the 1 year randomised, double-blind,
      double-dummy, parallel-group Prevention Of Exacerbations with Tiotropium in COPD
      (POET-COPD) trial, comparing the effects of treatment with tiotropium or
      salmeterol on exacerbations in 7376 patients with COPD. One blood sample was
      collected for pharmacogenetic testing from each patient who elected to
      participate in the substudy. Random assignment of patients to treatment groups
      was not stratified according to genotypes. Genomic DNA was extracted from whole
      blood specimens and samples were genotyped for the two SNPs, rs1042713 (Arg16Gly)
      and rs1042714 (Gln27Glu). All assays were done in technical duplicates and 10% of
      samples that were randomly chosen were repeated as technical duplicates in a
      second independent genotyping process. Our primary endpoint was the risk of a
      first exacerbation of COPD based on time to first exacerbation data. An
      exacerbation of COPD was defined as the increase or new onset of more than one
      symptom of COPD (cough, sputum, wheezing, dyspnoea, or chest tightness), with at
      least one of the symptoms lasting for 3 days or more and needing treatment with
      antibiotics or systemic glucocorticoids (moderate exacerbations), or admission to
      hospital (severe exacerbations). POET-COPD is registered with ClinicalTrials.gov,
      number NCT00563381. FINDINGS: 5125 patients gave informed consent for genotyping.
      The distributions of ADRB2 genotypes were well matched among groups.
      Polymorphisms at aminoacid 27 did not affect exacerbation outcomes. In the
      salmeterol group, patients with Arg16Arg genotype had a significantly reduced
      exacerbation risk compared with patients with Arg16Gly (p=0.0130) and Gly16Gly
      (p=0.0018) genotypes (proportion of patients with at least one exacerbation was
      32.3% in Arg16Arg, 39.8% in Arg16Gly, and 42.1% in Gly16Gly). By contrast,
      exacerbation risk was not modified by polymorphisms at aminoacid 16 in the
      tiotropium group. The effect of the Arg16Gly polymorphism on treatment response
      to salmeterol was dependent on the use of inhaled corticosteroids (ICS). In
      patients untreated with ICS at baseline, Arg16Gly and Arg16Arg genotypes were
      associated with significantly prolonged time to first exacerbation compared with
      Gly16Gly (vs Arg16Gly p=0.0164; Arg16Arg p=0.0316; proportion of patients with at
      least one exacerbation was 28.3% in Arg16Arg, 31.6% in Arg16Gly, and 39.2% in
      Gly16Gly), whereas in patients on ICS at baseline, only the Arg16Arg genotype was
      associated with significantly prolonged time to first exacerbation compared with
      Gly16Gly (p=0.0198; not Arg16Gly p=0.64; proportion of patients with at least one
      exacerbation was 35.9% in Arg16Arg, 46.7% in Arg16Gly, and 44.8% in Gly16Gly).
      The respiratory disorders, in particular worsening of COPD, were the most common
      serious adverse events. INTERPRETATION: Patients with the Arg16Arg genotype had
      better exacerbation outcomes in response to salmeterol than Gly16Gly and Arg16Gly
      genotypes, suggesting a potential differential Arg16Gly genotype effect on
      treatment response to longacting beta-agonists (LABAs). However, the use of ADRB2
      polymorphisms for predicting LABA treatment response is still limited and further
      prospective validation will be needed to advance the mechanistic understanding of
      beta-adrenergic polymorphisms and their association with clinical features of
      COPD. FUNDING: Boehringer Ingelheim and Pfizer.

PMID- 24461902
TI  - Mortality trends in chronic obstructive pulmonary disease in Europe, 1994-2010: a
      joinpoint regression analysis.
AB  - BACKGROUND: Findings from studies done over the past 20 years suggest that
      mortality from chronic obstructive pulmonary disease (COPD) is decreasing
      worldwide, but little information is available for trends in Europe. We aimed to
      describe COPD mortality trends by sex and calendar year for the period of 1994 to
      2010. METHODS: We extracted data for COPD deaths between 1994 and 2010 in the 27
      countries in the European Union (EU) from the statistical office of the EU
      (Eurostat), using the International Classification of Diseases 10 (ICD-10) codes
      J40-J44 and J47. We estimated age-standardised mortality rates (ASR), and
      analysed data using joinpoint regression, for women and men in the EU overall and
      by individual country for each year. We used the standard European population as
      the reference and present our findings as deaths per 100,000 person-years. We
      compared findings for each country with the EU average by calculating
      standardised rate ratios (SRR) and 95% CIs. FINDINGS: Between 1994 and 2010,
      there were 2,348,184 recorded COPD deaths in the EU. COPD mortality was higher in
      men than in women throughout the study period in all EU countries. In the EU
      overall, deaths per 100,000 population decreased in men almost linearly from
      90.07 in 1994 to 61.33 in 2010, and in women from 26.99 in 1994 to 25.15 in 2010,
      representing a narrowing in gender gap over the study period. Several countries
      had a higher SRR mortality than the EU average-eg, Ireland, Hungary, and Belgium
      for men and Denmark, the UK, and the Netherlands for women. Our joinpoint
      regression analysis identified no statistically significant changes in the trend
      for the whole EU, but several countries had changing trends over the study
      period. In men, we recorded a 2.56% constant and statistically significant
      decrease in ASRs in the EU. Five countries had an increase in ASR. Overall, in
      women, we recorded a 0.76% statistically significant decrease in ASRs. 14
      countries had an increase in ASR. INTERPRETATION: Our findings indicate a
      downward trend in COPD mortality in Europe between 1994 and 2010. The data also
      suggest a narrowing of the gap between COPD mortality in men and in women. The
      wide heterogeneity in mortality rates within European countries could serve as a
      reference to allow informed policy making. FUNDING: None.

PMID- 24461903
TI  - Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with
      chronic obstructive pulmonary disease: a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: The p38 MAPK pathway seems to be involved in pathogenesis of chronic
      obstructive pulmonary disease (COPD). Losmapimod is a potent and selective
      inhibitor of p38 MAPK. We assessed the effect of losmapimod on exercise tolerance
      in patients with COPD. METHODS: We did this randomised, parallel-group, placebo
      controlled trial at 46 secondary care centres in Argentina, Czech Republic,
      Estonia, Germany, Norway, South Korea, Ukraine, and USA between Nov 4, 2010, and
      Dec 22, 2011. We enrolled patients aged 40 years or older with moderate-to-severe
      COPD (6 min walking distance <350 m) who were current or previous smokers.
      Patients were randomly assigned (1:1:1:1) by a computer generated sequence to one
      of losmapimod 2.5 mg, 7.5 mg, or 15 mg, or placebo, twice daily for 24 weeks.
      Randomisation was stratified by country and exacerbation history (block size
      eight). Patients and investigators were masked to treatment assignment. The
      primary outcome was change in 6 min walking distance between baseline and week
      24, assessed in the intention-to-treat population. This study is registered with
      ClinicalTrial.gov, number NCT01218126. FINDINGS: We screened 886 patients, of
      whom 602 were enrolled and received treatment. The difference between the placebo
      group and the losmapimod groups for mean change of 6 min walk distance was not
      significant: -6.7 m (95% CI -18.2 to 4.9) for losmapimod 2.5 mg, -4.7 m (-16.1 to
      6.8) for losmapimod 7.5 mg, and -3.4 m (-15.1 to 8.2) for losmapimod 15 mg. The
      safety profile was much the same in each group, although drug-related adverse
      events were more common with losmapimod 7.5 mg (n=19, 13%) and losmapimod 15 mg
      (n=20, 13%) than with placebo (n=11, 7%) and losmapimod 2.5 mg (n=13, 9%). The
      most common serious adverse events were COPD exacerbation resulting in admission
      to hospital (eight patients [5%] taking placebo, six [4%] taking losmapimod 2.5
      mg, two [1%] taking losmapimod 7.5 mg, and three [2%] taking losmapimod 15 mg)
      and pneumonia (four [3%] vs 0 [0%] vs 1 [1%] vs 4 [3%]). INTERPRETATION:
      Losmapimod did not cause an improvement in exercise tolerance or lung function,
      despite being well-tolerated in this COPD population. FUNDING: GlaxoSmithKline.

PMID- 24461904
TI  - Respiratory infections in patients with cystic fibrosis undergoing lung
      transplantation.
AB  - Cystic fibrosis is an inherited disease characterised by chronic respiratory
      infections associated with bronchiectasis. Lung transplantation has helped to
      extend the lives of patients with cystic fibrosis who have advanced lung disease.
      However, persistent, recurrent, and newly acquired infections can be problematic.
      Classic cystic fibrosis-associated organisms, such as Staphylococcus aureus and
      Pseudomonas aeruginosa, are generally manageable post-transplantation, and are
      associated with favourable outcomes. Burkholderia cenocepacia poses particular
      challenges, although other Burkholderia species are less problematic. Despite
      concerns about non-tuberculous mycobacteria, especially Mycobacterium abscessus,
      post-transplantation survival has not been definitively shown to be less than
      average in patients with these infections. Fungal species can be prevalent before
      and after transplantation and are associated with high morbidity, so should be
      treated aggressively. Appropriate viral screening and antiviral prophylaxis are
      necessary to prevent infection with and reactivation of Epstein-Barr virus and
      cytomegalovirus and their associated complications. Awareness of drug
      pharmacokinetics and interactions in cystic fibrosis is crucial to prevent toxic
      effects and subtherapeutic or supratherapeutic drug dosing. With the large range
      of potential infectious organisms in patients with cystic fibrosis, infection
      control in hospital and outpatient settings is important. Despite its complexity,
      lung transplantation in the cystic fibrosis population is safe, with good
      outcomes if the clinician is aware of all the potential pathogens and remains
      vigilant by means of surveillance and proactive treatment. 

PMID- 24461905
TI  - Early diagnosis of IPF: time for a primary-care case-finding initiative?

PMID- 24461906
TI  - Developing compassion through a relationship centred appreciative leadership
      programme.
AB  - BACKGROUND: Recent attention in health care focuses on how to develop effective
      leaders for the future. Effective leadership is embodied in relationships and
      should be developed in and with staff and patients. This paper describes
      development, implementation and evaluation of an appreciative and relationship
      centred leadership programme carried out with 86 nursing staff covering 24 in
      patient areas within one acute NHS Board in Scotland. AIM OF LEADERSHIP
      PROGRAMME: The aim of the programme was to support staff to work together to
      develop a culture of inquiry that would enhance delivery of compassionate care.
      THEORETICAL UNDERPINNINGS: The 12 month Leadership Programme used the principles
      of appreciative relationship centred leadership. Within this framework
      participants were supported to explore relationships with self, patients and
      families, and with teams and the wider organisation using caring conversations.
      STRUCTURE OF PROGRAMME: Participants worked within communities of practice and
      action learning sets. They were supported to use a range of structured tools to
      learn about the experience of others and to identify caring practices that worked
      well and then explore ways in which these could happen more of the time. METHODS:
      A range of methods were used to evaluate impact of the programme including a
      culture questionnaire and semi structured interviews. Immersion crystallisation
      technique and descriptive statistics were used to analyse the data. FINDINGS: Key
      themes included; enhanced self-awareness, better relationships, greater ability
      to reflect on practice, different conversations in the workplace that were more
      compassionate and respectful, and an ethos of continuing learning and
      improvement. CONCLUSIONS: The programme supported participants to think in
      different ways and to be reflective and engaged participants rather than passive
      actors in shaping the cultural climate in which compassionate relationship
      centred care can flourish. Multidisciplinary programmes where the process and
      outcomes are explicitly linked to organisational objectives need to be considered
      in future programmes.

PMID- 24461907
TI  - Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified
      by exome sequencing and candidate gene screening.
AB  - Defects of mitochondrial oxidative phosphorylation (OXPHOS) are associated with a
      wide range of clinical phenotypes and time courses. Combined OXPHOS deficiencies
      are mainly caused by mutations of nuclear genes that are involved in
      mitochondrial protein translation. Due to their genetic heterogeneity it is
      almost impossible to diagnose OXPHOS patients on clinical grounds alone. Hence
      next generation sequencing (NGS) provides a distinct advantage over candidate
      gene sequencing to discover the underlying genetic defect in a timely manner. One
      recent example is the identification of mutations in MTFMT that impair
      mitochondrial protein translation through decreased formylation of Met-tRNA(Met).
      Here we report the results of a combined exome sequencing and candidate gene
      screening study. We identified nine additional MTFMT patients from eight families
      who were affected with Leigh encephalopathy or white matter disease,
      microcephaly, mental retardation, ataxia, and muscular hypotonia. In four
      patients, the causal mutations were identified by exome sequencing followed by
      stringent bioinformatic filtering. In one index case, exome sequencing identified
      a single heterozygous mutation leading to Sanger sequencing which identified a
      second mutation in the non-covered first exon. High-resolution melting curve
      based MTFMT screening in 350 OXPHPOS patients identified pathogenic mutations in
      another three index cases. Mutations in one of them were not covered by previous
      exome sequencing. All novel mutations predict a loss-of-function or result in a
      severe decrease in MTFMT protein in patients' fibroblasts accompanied by reduced
      steady-state levels of complex I and IV subunits. Being present in 11 out of 13
      index cases the c.626C>T mutation is one of the most frequent disease alleles
      underlying OXPHOS disorders. We provide detailed clinical descriptions on eleven
      MTFMT patients and review five previously reported cases. 

PMID- 24461908
TI  - Incidence and carrier frequency of Sandhoff disease in Saskatchewan determined
      using a novel substrate with detection by tandem mass spectrometry and molecular
      genetic analysis.
AB  - Sandhoff disease is a rare progressive neurodegenerative genetic disorder with a
      high incidence among certain isolated communities and ethnic groups around the
      world. Previous reports have shown a high occurrence of Sandhoff disease in
      northern Saskatchewan. Newborn screening cards from northern Saskatchewan were
      retrospectively screened in order to investigate the incidence and determine the
      carrier frequency of Sandhoff disease in these communities. PCR-based screening
      was conducted for the c.115delG (p.(Val39fs)) variant in the HEXB gene that was
      previously found in 4 Sandhoff disease patients from this area. The carrier
      frequency for this allele was estimated to be ~1:27. MS/MS-based screening of
      hexosaminidase activity along with genetic sequencing allowed for the
      identification of additional variants based on low total hexosaminidase activity
      and high % hexosaminidase A activity relative to c.115delG carriers. In total 4
      pathogenic variants were discovered in the population (c.115delG, c.619A>G,
      c.1601G>T, and c.1652G>A) of which two are previously unreported (c.1601G>T and
      c.1652G>A). The combined carrier frequency of these alleles in the study area was
      estimated at ~1:15. Based on the number of cases of Sandhoff disease from this
      area we estimate the incidence to be ~1:390 corresponding to a child being born
      with the disease every 1-2 years on average. The results from our study were then
      compared with variants in the HEXB gene from the genomes available from the 1000
      Genomes project. A total of 19 HEXB variants were found in the 1092 genomes of
      which 5 are suspected of having a deleterious effect on hexosaminidase activity.
      The estimated carrier frequency of Sandhoff disease in Saskatchewan at 1:15 is
      more than 3 times higher than the carrier frequency in the global sample provided
      by the 1000 Genomes project at 1:57.

PMID- 24461909
TI  - Developing model-based public health policy through knowledge translation: the
      need for a 'Communities of Practice'.
AB  - OBJECTIVES: The 2009 influenza A (H1N1) pandemic prompted public health agencies
      worldwide to respond in a context of substantial uncertainty. While many lessons
      around successful management strategies were learned during the influenza A
      (H1N1) pandemic, the usefulness and impact of mathematical models to optimize
      policy decisions in protecting public health were poorly realized. The authors
      explored the experiences of modellers and public health practitioners in trying
      to develop model-based public health policies in the management of the 2009
      influenza A (H1N1) pandemic in Canada. STUDY DESIGN: A qualitative case study
      design based on interviews and other textual data was used. METHODS: Individual
      interviews were conducted with mathematical modellers and public health
      professionals from academia and government health departments during the second
      wave of the 2009 influenza A (H1N1) pandemic (both prior to and following the
      vaccine roll-out), using a convergent interviewing process. Interviews were
      supplemented with discussions held during three separate workshops involving
      representatives from these groups on the role of modelling in pandemic
      preparedness and responses. NVivo9TM was used to analyse interview data and
      associated notes. RESULTS: Mathematical models were underutilized during the
      response phase of the 2009 influenza A (H1N1) pandemic, largely because many
      public health professionals were unaware of modelling infrastructure in Canada.
      Challenges were reflected in three ways: 1) the relevance of models to public
      health priorities; 2) the need for clear communication and plain language around
      modelling and its contributions and limitations; and 3) the need for increased
      trust and collaboration to develop strong working relationships. CONCLUSIONS:
      Developing a 'Communities of Practice' between public health professionals and
      mathematical modellers during inter-pandemic periods based on common targeted
      goals, using plain language, and where relationships between individuals and
      organizations are developed early, could be an effective strategy to assist the
      process of public health policy decision-making, particularly when characterized
      by high levels of uncertainty.

PMID- 24461910
TI  - Obesity in orthopedics and trauma surgery.
AB  - In 2012, 32.3% of the French population over 18 years of age was considered
      overweight (25 <= BMI<30 kg/m(2)) and 15% obese (BMI >= 30 kg/m(2)). Worldwide,
      2.8 million people die every year from the complications of obesity. In 2008, the
      prevalence of obesity was almost double that of 1980. Obesity is a genuine
      concern for the orthopedic surgeon, as it affects bones and soft tissues on the
      biomechanical and biochemical level. In traumatology, low-energy trauma is more
      frequent in obese patients and induces complex comminutive fractures of the
      extremities. In orthopedics, obesity is an independent risk factor for
      osteoarthritis, particularly for the knee joint. The goals of this review are to
      describe specific aspects of the care of obese patients in trauma and orthopedics
      surgery during the pre-, intra- and postoperative periods, as well as the risk
      benefit ratio related to the treatment of the obese patients.

PMID- 24461911
TI  - Articular fractures of the distal humerus.
AB  - Distal humeral fractures represent 2% of all adult elbow fractures. Injury
      mechanisms include high-energy trauma with skin involvement, and low energy
      trauma in osteoporotic bone. Treatment goals are anatomical restoration in young,
      high-demand patients and quick recovery of activities of daily living in the
      elderly. Complete fractures are relatively easy to diagnose, but partial intra
      articular fractures are not. The clinical diagnosis must take into account
      potential complications such as open injuries and ulnar nerve trauma. Standard X
      rays with additional distraction series in the operating room are sufficient in
      complete articular fracture cases. Partial intra-articular fractures will need CT
      scan and 3D reconstruction to fully evaluate the involved fragments. SOFCOT,
      AO/OTA and Dubberley classifications are the most useful for describing fractures
      and selecting treatment. Surgery is the optimal treatment and planning is based
      on fracture type. Complete fractures are treated using a posterior approach.
      Triceps management is a function of fracture lines and type of fixation planned.
      Constructs using two plates at 90 degrees  or 180 degrees  are the most stable,
      with additional frontal screw for intercondylar fractures. Elbow arthroplasty may
      be indicated in selected patients, having severely communited distal humerus
      fractures and osteoporotic bone. Open fractures make fixation and wound
      management more challenging and unfortunately have poorer outcomes. Other
      complications are elbow stiffness, non-union, malunion and heterotopic
      ossification. 

PMID- 24461912
TI  - Epileptic features in Cornelia de Lange syndrome: case report and literature
      review.
AB  - INTRODUCTION: Cornelia de Lange syndrome is a rare genetic disease, caused by
      mutations in three known different genes: NIBPL (crom 5p), SMC1A (crom X) and
      SMC3 (crom 10q), that account for about 65% of cases. This syndrome is
      characterized by distinctive facial features, psychomotor delay, growth
      retardation since the prenatal period (second trimester of pregnancy), hands and
      feet abnormalities, and involvement of other organs/systems. SMC1A and SMC3
      mutations are responsible for a mild phenotype of the syndrome. METHODS: We
      report the electroclinical features of epilepsy in a child with a mild Cornelia
      de Lange syndrome and furthermore we reviewed the descriptions of the epileptic
      findings available in the literature in patients with such syndrome. RESULTS: A
      large heterogeneity of the epileptic findings in the literature is reported.
      CONCLUSION: The presence of epilepsy could be related to pathophysiological
      factors independent of those implicated in the characterization of main classical
      phenotypic features. A more detailed description of the epileptic findings could
      help clinicians in the diagnosis of this syndrome in those cases lacking of the
      typical features.

PMID- 24461913
TI  - Vaccination with recombinant adenoviruses expressing Ebola virus glycoprotein
      elicits protection in the interferon alpha/beta receptor knock-out mouse.
AB  - The resistance of adult immunocompetent mice to infection with ebolaviruses has
      led to the development of alternative small animal models that utilise
      immunodeficient mice, for example the interferon alpha/beta receptor knock-out
      mouse (IFNR(-/-)). IFNR(-/-) mice have been shown to be susceptible to infection
      with ebolaviruses by multiple routes but it is not known if this murine model is
      suitable for testing therapeutics that rely on the generation of an immune
      response for efficacy. We have tested recombinant adenovirus vectors for their
      ability to protect IFNR(-/-) mice from challenge with Ebola virus and have
      analysed the humoral response generated after immunisation. The recombinant
      vaccines elicited good levels of protection in the knock-out mouse and the
      antibody response in IFNR(-/-) mice was similar to that observed in vaccinated
      wild-type mice. These results indicate that the IFNR(-/-) mouse is a relevant
      small animal model for studying ebolavirus-specific therapeutics. 

PMID- 24461914
TI  - Effects of the intestinal microbiome on constituents of red meat and egg yolks: a
      new window opens on nutrition and cardiovascular disease.

PMID- 24461915
TI  - Sequencing: the next generation--what is the role of whole-exome sequencing in
      the diagnosis of familial cardiovascular diseases?

PMID- 24461916
TI  - Exploring the role of aldosterone in right ventricular function.

PMID- 24461917
TI  - Endothelin as a marker of risk in patients with chest pain?

PMID- 24461918
TI  - Functional mitral regurgitation: current understanding and approach to
      management.
AB  - Functional mitral regurgitation (FMR) is a challenging clinical entity that
      frequently complicates ischemic and nonischemic cardiomyopathy. The underlying
      pathophysiology of FMR is caused primarily by ventricular and subvalvular
      apparatus dysfunction which causes failure of proper leaflet coaptation.
      Echocardiography is the primary modality used in diagnosis and characterization
      of FMR. Echocardiography allows for assessment of valvular and ventricular
      structures and their interaction. FMR portends a poor prognosis, because it is
      frequently associated with increased morbidity and mortality. The optimal
      management of FMR involves an individualized approach that incorporates medical
      therapy and consideration of surgical, percutaneous, and resynchronization
      therapies according to the severity of regurgitation, presence of symptoms,
      option for revascularization, and the degree of ventricular remodelling. 

PMID- 24461919
TI  - Exome sequencing identifies a novel variant in ACTC1 associated with familial
      atrial septal defect.
AB  - BACKGROUND: The genetics of congenital heart disease (CHD) remain incompletely
      understood. Exome sequencing has been successfully used to identify disease
      causing mutations in familial disorders in which candidate gene analyses and
      linkage mapping have failed. METHODS: We studied a large family characterized by
      autosomal dominant isolated secundum atrial septal defect (ASD) (MIM No. 612794).
      Candidate gene resequencing and linkage analysis were uninformative. RESULTS:
      Whole-exome sequencing of 2 affected family members identified 44 rare shared
      variants, including a nonsynonymous mutation (c.532A>T, p.M178L, NM_005159.4) in
      alpha-cardiac actin (ACTC1). This mutation was absent from 1834 internal controls
      as well as from the 1000 Genomes and the Exome Sequencing Project (ESP)
      databases, but predictions regarding its effect on protein function were
      divergent. However, p.M178L was the only rare mutation segregating with disease
      in our family. CONCLUSIONS: Our results provide further evidence supporting a
      causative role for ACTC1 mutations in ASD. Massively parallel sequencing of the
      exome allows for the detection of novel rare variants causing CHD without the
      limitations of a candidate gene approach. When mutation prediction algorithms are
      not helpful, studies of familial disease can help distinguish rare pathologic
      mutations from benign variants. Consideration of the family history can lead to
      genetic insights into CHD.

PMID- 24461920
TI  - Abnormal regulation of renin angiotensin aldosterone system is associated with
      right ventricular dysfunction in hypertension.
AB  - BACKGROUND: Right ventricular dysfunction (RVD) is a major predictor of
      cardiovascular mortality. Inadequate suppression of the renin-angiotensin
      aldosterone system (RAAS) after postural manoeuvres favours alterations of left
      ventricular (LV) function. The effects of RAAS dysregulation on RV performance
      remain elusive. The present study investigated RV function in hypertensive
      patients with or without altered RAAS activation. METHODS: Plasma renin activity
      (PRA) and plasma aldosterone concentration (PAC) were measured in 104 newly
      diagnosed hypertensive patients after both supine and upright positioning to
      assess dynamic changes of RAAS induced by antigravitational stress. Twenty-four
      hour ambulatory blood pressure monitoring and echocardiographic evaluation of the
      right ventricle including tissue Doppler imaging (TDI) were performed. Patients
      were divided as follows: (1) normal PRA and PAC (N group [n = 58]), (2)
      suppressible RAAS after supine positioning (SR group [n = 24]), and (3),
      nonsuppressible RAAS (NSR group [n = 22]). RVD was identified by the TDI-derived
      myocardial performance index (MPI) calculated with a multisegmental approach.
      RESULTS: Patients in the NSR group had reduced indices of RV function compared
      with patients in the N and SR groups. MPI of the right ventricle as well as
      prevalence of RVD were also significantly higher in the NSR group. Regression
      models showed that inadequate RAAS suppression was independently associated with
      RVD, regardless of blood pressure values and LV dysfunction (LVD). CONCLUSIONS:
      Patients without supine normalization of RAAS display a significant impairment of
      RV function. Our findings suggest that a dynamic RAAS evaluation may help to
      identify hypertensive patients at higher risk of RVD.

PMID- 24461921
TI  - Utility of C-terminal proendothelin in the early diagnosis and risk
      stratification of patients with suspected acute myocardial infarction.
AB  - BACKGROUND: Endothelial dysfunction plays a major role in cardiovascular
      diseases, including acute myocardial infarction (AMI). However, its
      quantification has not been available as a clinical tool. METHODS: In a
      prospective international multicentre study, we analyzed the diagnostic and
      prognostic utility of endothelial dysfunction as quantified by C-terminal
      proendothelin-1 (CT-proET-1) in 658 consecutive patients presenting with
      suspected AMI. The final diagnosis was adjudicated by 2 independent
      cardiologists. Patients were followed long-term for mortality. RESULTS: The
      adjudicated final diagnosis was AMI in 145 patients (22%). The diagnostic
      performance of CT-proET-1 for AMI was moderate; its area under the receiver
      operating characteristic (ROC) curve amounted to 0.66 (95% confidence interval
      [CI], 0.61-0.72; P < 0.001). There was no significant increase in the AUC when CT
      proET-1 was added to either cardiac troponin T (cTnT) or high-sensitivity cTnT
      (hs-cTnT). Seventy four percent of patients who died during the first 24 months
      (n = 50) were in the fourth quartile of the CT-proET-1 presentation value (>82
      pmol/L). The prognostic accuracy of CT-proET-1 regarding mortality was tantamount
      to that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outperformed
      cTnT and hs-cTnT both in patients with AMI and in patients without acute coronary
      syndrome. CT-proET-1 at presentation yielded high prognostic accuracy that was
      similar to that of the Thrombolysis in Myocardial Infarction (TIMI) and Global
      Registry of Acute Coronary Events (GRACE) risk scores. The TIMI risk score could
      be significantly improved by adding CT-proET-1 (integrated discriminatory
      improvement [IDI] of 0.074 P = 0.004). CONCLUSIONS: Use of CT-proET-1 improves
      risk stratification of unselected patients with suspected AMI. CT-proET-1 did not
      provide additional diagnostic value.

PMID- 24461922
TI  - Relationship between fragmented QRS and no-reflow, infarct size, and peri-infarct
      zone assessed using cardiac magnetic resonance in patients with myocardial
      infarction.
AB  - BACKGROUND: The relation between fragmented QRS complex (fQRS) and cardiac
      magnetic resonance parameters is poorly documented in ischemic cardiopathy.
      METHODS: Among 209 consecutive patients, those with fQRS were compared with those
      without fQRS. Cardiac magnetic resonance studies with late gadolinium-enhanced
      sequences were done during the week after acute myocardial infarction. RESULTS:
      fQRS was present in 113 (54%) patients, and associated with a significantly lower
      left ventricular ejection fraction, increased left ventricular volumes, a larger
      infarct size (IS), and a larger peri-infarct zone. Microvascular obstruction was
      more frequent in patients with fQRS (62% vs 45%; P = 0.014) and the extent of the
      microvascular obstruction was significantly larger (1.6% [range, 0.0-4.4] vs 0.0
      [range, 0.0-2.1]; P = 0.004). Finally, the transmurality score in the 2 study
      populations was identical (48% vs 47%; P = 0.895). In multivariate logistic
      regression analysis, only IS (odds ratio [OR], 1.06; 95% confidence interval
      [CI], 1.03-1.09; P < 0.001), systolic blood pressure (OR, 1.02; 95% CI, 1.01
      1.04; P < 0.001), and left ventricular end-systolic volume (OR, 1.02; 95% CI,
      1.00-1.03; P = 0.013) remained independent predictors of fQRS. CONCLUSIONS: This
      study revealed that fQRS was associated with increased IS, myocardial perfusion
      abnormalities, decreased left ventricular ejection fraction, and increased left
      heart volumes. These findings show that fQRS is a reliable marker of infarct size
      and acute ventricular remodelling.

PMID- 24461923
TI  - Predictors of radial artery size in patients undergoing cardiac catheterization:
      insights from the Good Radial Artery Size Prediction (GRASP) study.
AB  - BACKGROUND: Radial artery occlusion occurs after transradial cardiac
      catheterization or percutaneous coronary intervention. Although use of a sheath
      larger than the artery is a risk factor for radial artery occlusion, radial
      artery size is not routinely measured. We aimed to identify bedside predictors of
      radial artery diameter. METHODS: Using ultrasound, we prospectively measured
      radial, ulnar, and brachial artery diameters of 130 patients who presented for
      elective percutaneous coronary intervention or diagnostic angiography. Using
      prespecified candidate variables we used multivariable linear regression to
      identify predictors of radial artery diameter. RESULTS: Mean internal diameters
      of the right radial, ulnar, and brachial arteries were 2.44 +/- 0.60, 2.14 +/-
      0.53, and 4.50 +/- 0.88 mm, respectively. Results for the left arm were similar.
      The right radial artery was larger in men than in women (2.59 vs 1.91 mm; P <
      0.001) and smaller in patients of South Asian descent (2.00 vs 2.52 mm; P <
      0.001). Radial artery diameter correlated with wrist circumference (r(2) = 0.26;
      P < 0.001) and shoe size (r(2) = 0.25; P < 0.001) and weakly correlated with
      height (r(2) = 0.14; P < 0.001), weight (r(2) = 0.18; P < 0.001), body mass index
      (r(2) = 0.07; P = 0.002), and body surface area (r(2) = 0.22; P < 0.001). The
      independent predictors of a larger radial artery were wrist circumference (r(2) =
      0.26; P < 0.001), male sex (r(2) = 0.06; P < 0.001), and non-South Asian ancestry
      (r(2) = 0.05; P = 0.006; final model r(2) = 0.37; P < 0.001). A risk score using
      these variables predicted radial artery diameter (c-statistic, 0.71).
      CONCLUSIONS: Wrist circumference, male sex, and non-South Asian ancestry are
      independent predictors of increased radial artery diameter. A risk score using
      these variables can identify patients with small radial arteries.

PMID- 24461924
TI  - Managing novel oral anticoagulants in patients with atrial fibrillation
      undergoing device surgery: Canadian survey.
AB  - BACKGROUND: Approximately 10% of patients who undergo surgical procedures require
      chronic oral anticoagulation. Physicians must balance the thromboembolic and
      bleeding risks to make informed decisions on whether to continue anticoagulant
      medication. Evidence is lacking regarding the perioperative management of novel
      oral anticoagulant (NOAC) agents. This survey aims to describe the management of
      perioperative NOAC use during device implantation by Canadian centres. METHODS: A
      Web-based tool was used to survey all Canadian adult pacemaker/defibrillator
      implant centres. The survey collected data regarding the perioperative management
      of NOACs in atrial fibrillation patients at high risk for thromboembolism who
      undergo device implantation. RESULTS: Twenty-two centres performed approximately
      14,971 device implants; 1150 (8%) of these implants were in patients who were
      prescribed a NOAC. In 82% of centres, the NOAC is discontinued in anticipation of
      device implantation; 73% of these centres do not bridge with heparin. In patients
      with normal renal function at high risk of thromboembolic events (Congestive
      Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack;
      CHADS2 >= 2), 72% of the centres restart the NOAC within 48 hours of the
      procedure. For patients with abnormal renal function (glomerular filtration rate
      < 80 mL/min), the timing of NOAC discontinuation is variable. Hematoma rates vary
      from 0 to 30%. CONCLUSIONS: Most Canadian centres perform device implantation
      with NOAC interruption without the use of bridging. The timing of stopping and
      restarting anticoagulation and incidence of bleeding complications is variable.
      These findings emphasize the need for randomized controlled studies to guide the
      optimal approach to management of NOACs during device implantation.

PMID- 24461925
TI  - Use and misuse of ezetimibe: analysis of use and cost in Saskatchewan, a Canadian
      jurisdiction with broad access.
AB  - BACKGROUND: Saskatchewan is the only Canadian province that lists ezetimibe for
      open formulary access even though it is a second-line agent for lowering
      cholesterol. METHODS: A retrospective analysis of ezetimibe use in Saskatchewan
      between 2002 and 2011 was carried out using provincial health administrative
      databases. Overall use and costs of ezetimibe were described over time. Among new
      users of ezetimibe, the percentage who received the drug as first-line
      monotherapy was estimated. First-line monotherapy was defined as no statin
      dispensations in the 365 days before and the 60 days after the first ezetimibe
      dispensation. Potential predictors of first-line monotherapy were assessed using
      generalized linear mixed-effect models. RESULTS: In 2004, ezetimibe represented
      2.5% of cholesterol-lowering dispensations. In 2011, its use increased to 8.8% of
      cholesterol-lowering dispensations and 13.2% of the total cost of cholesterol
      lowering agents. Overall, ezetimibe was used as first-line monotherapy in 23% of
      all new users (4024 of 17,475 patients). Approximately half of all cases of first
      line monotherapy were prescribed by 10.4% (112 of 1074) of prescribers in the
      cohort. Patients who had experienced previous acute coronary syndrome or who had
      undergone coronary revascularization procedures were significantly less likely to
      receive first-line monotherapy. CONCLUSIONS: A high proportion of ezetimibe's use
      is not in accordance with evidence-based recommendations. Suboptimal prescribing
      could partially explain current patterns of use; however, other factors such as
      medication nonadherence may have played an important role. Restricting ezetimibe
      use in the provincial formulary in addition to improving prescribers' awareness
      through academic detailing should be considered.

PMID- 24461926
TI  - Reply to letter from Katz--early repair of congenital heart disease associated
      with an increased rate of ADHD symptoms: a response to the call for additional
      information.

PMID- 24461927
TI  - Biophoton signal transmission and processing in the brain.
AB  - The transmission and processing of neural information in the nervous system plays
      a key role in neural functions. It is well accepted that neural communication is
      mediated by bioelectricity and chemical molecules via the processes called
      bioelectrical and chemical transmission, respectively. Indeed, the traditional
      theories seem to give valuable explanations for the basic functions of the
      nervous system, but difficult to construct general accepted concepts or
      principles to provide reasonable explanations of higher brain functions and
      mental activities, such as perception, learning and memory, emotion and
      consciousness. Therefore, many unanswered questions and debates over the neural
      encoding and mechanisms of neuronal networks remain. Cell to cell communication
      by biophotons, also called ultra-weak photon emissions, has been demonstrated in
      several plants, bacteria and certain animal cells. Recently, both experimental
      evidence and theoretical speculation have suggested that biophotons may play a
      potential role in neural signal transmission and processing, contributing to the
      understanding of the high functions of nervous system. In this paper, we review
      the relevant experimental findings and discuss the possible underlying mechanisms
      of biophoton signal transmission and processing in the nervous system. 

PMID- 24461928
TI  - Trajectories in functional recovery for patients receiving inpatient
      rehabilitation for unilateral hip or knee replacement.
AB  - The purpose of this study was to explore trajectories of recovery in patients
      with lower extremity joint replacements receiving post-acute rehabilitation. A
      retrospective cohort design was used to examine data from the Uniform Data System
      for Medical Rehabilitation (UDSMR(r)) for 7434 patients with total knee
      replacement (TKR) and 4765 patients with total hip replacement (THR) who received
      rehabilitation from 2008 to 2010. Functional Independence Measure (FIM)TM
      instrument ratings were obtained at admission, discharge, and 80-180 days after
      discharge. Random coefficient regression analyses using linear mixed models were
      used to estimate mean ratings for items within the four motor subscales (self
      care, sphincter control, transfers, and locomotion) and the cognitive domain of
      the FIM instrument. Mean improvements at discharge for motor items ranged from
      1.16 (95% confidence interval [CI]: 1.14, 1.19) to 2.69 (95% CI: 2.66, 2.71)
      points for sphincter control and locomotion, respectively. At follow-up mean
      motor improvements ranged from 2.17 (95% CI: 2.15, 2.20) to 4.06 (95% CI: 4.03,
      4.06) points for sphincter control and locomotion, respectively. FIM cognition
      yielded smaller improvements: discharge=0.47 (95% CI: 0.46, 0.48); follow-up=0.83
      (95% CI: 0.81, 0.84). Persons who were younger, female, non-Hispanic white,
      unmarried, with fewer comorbid conditions, and who received a TKR demonstrated
      slightly higher functional motor ratings. Overall, patients with unilateral knee
      or hip replacement experienced substantial improvement in motor functioning both
      during and up to six months following inpatient rehabilitation.

PMID- 24461929
TI  - Y-box binding protein 1--a prognostic marker and target in tumour therapy.
AB  - Y-box binding protein 1 (YB-1) is a multifunctional protein involved in various
      cellular processes including both transcriptional and translational regulation of
      target gene expression. Significantly increased YB-1 levels have been reported in
      a number of human malignancies and shown to be associated with poor prognosis and
      disease recurrence. Indeed, YB-1 can act as a versatile oncoprotein playing an
      important role in tumour cell proliferation and progression. Consequently, YB-1
      not only proves to be a good prognostic tumour marker, but also may be a
      promising emerging molecular target for the development of new therapeutical
      strategies. In this review, we discuss both the role of YB-1 in cancer and
      specifically in malignant melanoma as well as possible translations into the
      clinics derived thereof. 

PMID- 24461930
TI  - The role of maternal input in the development of wh-question comprehension in
      autism and typical development.
AB  - Social deficits have been implicated in the language delays and deficits of
      children with autism (ASD); thus, the extent to which these children use language
      input in social contexts similarly to typically developing (TD) children is
      unknown. The current study investigated how caregiver input influenced the
      development of wh-question comprehension in TD children and language-matched
      preschoolers with ASD. Children were visited at four-month intervals over 1.5
      years; mother-child play sessions at visits 1-2 were coded for maternal wh
      question use. At visits 3-5 children watched videos in the Intermodal
      Preferential Looking paradigm, to assess their comprehension of subject and
      object wh-questions. Mothers' use of wh-questions with verbs and complex wh
      questions positively predicted wh-question comprehension in the TD group; in
      contrast, mothers' use of wh-questions with 'be' as the main verb negatively
      predicted wh-question comprehension in the ASD group. Thus, TD children and
      children with ASD appear to use their linguistic input differently.

PMID- 24461931
TI  - Accuracy of prenatal smoking data from Washington State birth certificates in a
      population-based sample with cotinine measurements.
AB  - PURPOSE: To assess the accuracy of smoking data in contemporary U.S. birth
      certificates. METHODS: We compared data on prenatal smoking as reported on
      Washington State birth certificates to cotinine measured in archived newborn
      screening dried blood spots for 200 infants born in 2007 (100 randomly selected
      from births to self-reported nonsmokers and 100 born to self-reported smokers).
      We estimated the sensitivity of the birth certificate data to identify prenatal
      smokers and the precision with which self-identified third trimester smokers
      report smoking levels. RESULTS: Infants born to two (2%) mothers who reported
      they did not smoke during the pregnancy had whole blood cotinine concentrations
      consistent with active smoking by the mother (sensitivity 85%). Sensitivity of
      the birth certificate to identify reported smokers who continued to smoke
      throughout pregnancy was similar (89%). Among self-identified third trimester
      smokers whose infants' specimens were collected shortly after delivery, Spearman
      rho between infant cotinine and maternal-reported cigarettes/day in the third
      trimester was 0.54. CONCLUSIONS: Birth certificates may represent a viable option
      for assessing prenatal smoking status, and possibly smoking cessation and level
      among smokers, in epidemiologic studies sufficiently powered to overcome a
      moderate amount of exposure measurement error.

PMID- 24461932
TI  - Field substitution of nonresponders can maintain sample size and structure
      without altering survey estimates-the experience of the Italian behavioral risk
      factors surveillance system (PASSI).
AB  - PURPOSE: Field substitution of nonrespondents can be used to maintain the planned
      sample size and structure in surveys but may introduce additional bias. Sample
      weighting is suggested as the preferable alternative; however, limited empirical
      evidence exists comparing the two methods. We wanted to assess the impact of
      substitution on surveillance results using data from Progressi delle Aziende
      Sanitarie per la Salute in Italia-Progress by Local Health Units towards a
      Healthier Italy (PASSI). METHODS: PASSI is conducted by Local Health Units (LHUs)
      through telephone interviews of stratified random samples of residents.
      Nonrespondents are replaced with substitutes randomly preselected in the same LHU
      stratum. We compared the weighted estimates obtained in the original PASSI sample
      (used as a reference) and in the substitutes' sample. The differences were
      evaluated using a Wald test. RESULTS: In 2011, 50,697 units were selected: 37,252
      were from the original sample and 13,445 were substitutes; 37,162 persons were
      interviewed. The initially planned size and demographic composition were
      restored. No significant differences in the estimates between the original and
      the substitutes' sample were found. CONCLUSIONS: In our experience, field
      substitution is an acceptable method for dealing with nonresponse, maintaining
      the characteristics of the original sample without affecting the results. This
      evidence can support appropriate decisions about planning and implementing a
      surveillance system.

PMID- 24461933
TI  - Sleep architecture in school-aged children with primary snoring.
AB  - OBJECTIVE: We aimed to examine if sleep architecture was altered in school-aged
      children with primary snoring (PS). METHODS: Children ages 6 to 13 years from 13
      primary schools were randomly recruited. A validated obstructive sleep apnea
      (OSA) screening questionnaire was completed by their parents. Children at high
      risk for OSA and a randomly chosen low-risk group were invited to undergo
      overnight polysomnography (PSG) and clinical examination. Participants were
      classified into healthy controls, PS, mild OSA, and moderate to severe OSA (MS
      OSA) groups for comparison. RESULTS: A total of 619 participants underwent PSG
      (mean age, 10.0 +/- 1.8 years; 396 (64.0%) boys; 524 (84.7%) prepubertal). For
      the cohort as a whole, there were no significant differences in measures of sleep
      architecture between PS and nonsnoring healthy controls. In the multiple
      regression model, percentage of nonrapid eye movement (NREM) stage 1 (N1) sleep
      had a significantly positive association, whereas percentage of slow-wave sleep
      (SWS) had a significantly negative association with sleep-disordered breathing
      (SDB) severity after controlling for age, gender, body mass index (BMI) z score,
      and pubertal status. In prepubertal children with PS, no significant disruption
      of sleep architecture was found. However, pubertal adolescent PS participants had
      significantly higher adjusted percentage of N1 sleep and wake after sleep onset
      (WASO) compared to healthy controls. CONCLUSIONS: PS did not exert significant
      adverse influences on normal sleep architecture in prepubertal school-aged
      children. Nevertheless, pubertal adolescents with PS had increased N1 sleep and
      WASO.

PMID- 24461934
TI  - New surgical approaches for urinary incontinence in women.
AB  - Urinary incontinence (UI) is highly prevalent and common complaint. A large
      proportion of women with UI can be correctly diagnosed by their symptoms alone.
      First line of treatment should follow conservative route in a form of pelvic
      floor muscle training for stress UI and bladder training for the urgency UI. If
      conservative management is ineffective, medical and surgical treatment is the
      next considered. For the treatment of over-active bladder and urgency UI, intra
      vesical injections of botulinum toxin A, utilising a flexible or rigid cystoscope
      has become an established treatment. An alternative to the use of onaBoNTA is
      sacral nerve stimulation (SNS). Vaginal tapes/slings procedures have become
      treatment of choice for stress UI. Different approaches of introduction of
      vaginal tape can be used, including retropubic 'bottom-up' (TVT), and
      transobturator 'inside-out' (TVT-O), or 'outside-in' (TOT). TVT and TVT-O/TOT
      seem comparable although there are differences in complications (bladder injury
      with TVT vs. leg pain with TVT-O/TOT). Recently single incision approaches have
      been introduced whereby the vaginal tape is inserted via a single vaginal
      incision. Based on current evidence, single incision slings are not recommended.
      Individual clinicians should decide which to use based on expertise and
      experience, nevertheless, bladder injuries are probably less of an issue than leg
      pain. 

PMID- 24461935
TI  - Immobilized purine nucleoside phosphorylase from Aeromonas hydrophila as an on
      line enzyme reactor for biocatalytic applications.
AB  - We described the development of a biochromatographic system which uses a purine
      nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) for the evaluation of
      the substrate specificity on nucleoside libraries. AhPNP has been covalently
      immobilized on a fused silica Open Tubular Capillary (OTC) via Schiff base
      chemistry. The resulting bioreactor has been characterized by the determination
      of kinetic constants (Km and Vmax) for a natural substrate (inosine) and then
      assayed versus all natural purine (deoxy)ribonucleosides and a small library of 6
      substituted purine ribosides. Characterization of the bioreactor has been carried
      out through a bidimensional chromatographic system with the sample on-line
      transfer from the bioreactor to the analytical column for the separation and
      quantification of substrate and product. Comparison with the soluble enzyme
      showed that the AhPNP-based bioreactor is reliable as the same ranking order,
      with respect to the standard activity assay, was obtained. The stability of the
      IMER was also assessed and the system was found to be stable up to 60 reactions. 

PMID- 24461936
TI  - [An uncommon cause of hematemesis in children: factor XI deficiency].
AB  - Congenital factor XI deficiency, also called hemophilia C, is a rare coagulation
      disorder that is particularly common in Ashkenazi Jews. Individuals with factor
      XI deficiency may or may not have a mild bleeding tendency, which is typically
      provoked by surgery or trauma. We report the case of a 5.5-year-old girl who
      presented with abdominal pain, vomiting, and hematemesis. Biological tests showed
      a prolonged activated partial thromboplastin time (aPTT) of 113 s (control=29 s)
      caused by a constitutional factor Xl deficiency (2.7%). The progression was
      spontaneously favorable. 

PMID- 24461937
TI  - A near-fatal case of exercise-associated hyponatremia.
AB  - A 42-year-old woman presented to our emergency department with headache, nausea,
      and confusion after completing an Ironman triathlon. She performed the race at a
      slow pace, in hot and dry weather. The first medical examination reported
      confusion with a Glasgow Coma Scale score of 13. A few minutes later, she
      presented with seizures. A cerebral computed tomographic (CT) scan showed major
      cerebral edema. Blood analysis showed severe acute hyponatremia (123 mEq/L) with
      hypotonicity (255 mEq/L). Her clinical condition quickly worsened, leading to a
      Glasgow Coma Scale score of 3 with fixed dilated pupils. After intubation and
      mechanical ventilation, she was transferred to the intensive care unit. A
      transcranial Doppler ultrasonography (TCD) showed intracranial hypertension signs
      motivating emergency osmotherapy by infusion of 20% mannitol over 15 minutes. To
      guide the therapeutics, an intracranial pressure monitoring was inserted, showing
      a value of 30 mm Hg. A few minutes later, intracranial pressure (ICP) increased
      to 68 mm Hg with a low cerebral perfusion pressure. Concomitantly, another TCD
      reported critical flows with poor cerebral perfusion. A second infusion of
      mannitol led to an ICP lowering and a decrease in pupil size after 10 minutes.
      During the next hours, the patient stayed stable without further intervention.
      Sixteen hours later, natremia was normal, mainly due to hyperdiuresis. On day 2,
      the tracheal tube was removed. A cerebral CT scan showed disappearance of
      cerebral edema. One month later, the patient had good recovery apart from some
      residual memory problems. Six months later, she was able to come back to work.

PMID- 24461938
TI  - Blood protein coating of gold nanoparticles as potential tool for organ
      targeting.
AB  - Nanoparticles (NP) and nanoparticulated drug delivery promise to be the
      breakthrough for therapy in medicine but raise concerns in terms of nanotoxicity.
      We present quantitative murine biokinetics assays using polyelectrolyte
      multilayer-coated gold NP (AuNP, core diameter 15 and 80 nm; (198)Au radio
      labeled). Those were stably conjugated either with human serum albumin (alb-AuNP)
      or apolipoprotein E (apoE-AuNP), prior to intravenous injection. We compare the
      biokinetics of protein-AuNP-conjugates with citrate-stabilized AuNP (cit-AuNP).
      Biokinetics was complemented with histology in organs with high AuNP content
      using 15 nm double fluorescently-labeled alb-AuNP-conjugates. Protein conjugation
      massively reduced liver retention (alb-AuNP: 52%, apoE-AuNP: 72%, cit-AuNP: >95%,
      at 19 h and 48 h) when compared to cit-AuNP. The protein conjugates were retained
      in lungs (alb-AuNP (18%) and spleen (alb-AuNP (16%), apoE-AuNP (21%) at 19 h. Alb
      AuNP show significantly increased fractions in lungs (factors: 60 (30 min); 111
      (19 h); 235 (48 h) and brain (factors: 70 (30 min); 90 (19 h); >200 (48 h)
      compared to cit-AuNP (control) - or even to apoE-AuNP. The influence of protein
      conjugation on the biodistribution disappears for 80 nm AuNP comparing to
      control. Histologically, the 15 nm alb-AuNP are mainly located in the endothelium
      of brain, lungs, liver and kidneys after 30 min, while at 19 h they moved deeper
      into the parenchyma e.g. in hippocampus. Our study clearly suggests that stable
      conjugation of AuNP with albumin and apoE prior to intravenous administration
      increases specificity and efficiency of NP in diseased target-organs thus
      suggesting a potential role in nanomedicine and nanopharmacology.

PMID- 24461939
TI  - The behavior of neuronal cells on tendon-derived collagen sheets as potential
      substrates for nerve regeneration.
AB  - Peripheral nervous system injuries result in a decreased quality of life, and
      generally require surgical intervention for repair. Currently, the gold standard
      of nerve autografting, based on the use of host tissue such as sensory nerves is
      suboptimal as it results in donor-site loss of function and requires a secondary
      surgery. Nerve guidance conduits fabricated from natural polymers such as
      collagen are a common alternative to bridge nerve defects. In the present work,
      tendon sections derived through a process named bioskiving were studied for their
      potential for use as a substrate to fabricate nerve guidance conduits. We show
      that cells such as rat Schwann cells adhere, proliferate, and align along the
      fibrous tendon substrate which has been shown to result in a more mature
      phenotype. Additionally we demonstrate that chick dorsal root ganglia explants
      cultured on the tendon grow to similar lengths compared to dorsal root ganglia
      cultured on collagen gels, but also grow in a more oriented manner on the tendon
      sections. These results show that tendon sections produced through bioskiving can
      support directional nerve growth and may be of use as a substrate for the
      fabrication of nerve guidance conduits. 

PMID- 24461941
TI  - A technique for fabricating single screw-retained implant-supported interim
      crowns in conjunction with implant surgery.
AB  - This article presents an intraoral technique for fabricating single screw
      retained implant-supported interim crowns immediately after surgical implant
      placement in extraction sites. The technique may be used with any implant system
      that provides a provisional abutment or an open-tray impression coping that can
      be modified for use as a provisional abutment. 

PMID- 24461940
TI  - Protective effect of an immune-modulating diet comprising whey peptides and
      fermented milk products on indomethacin-induced small-bowel disorders in rats.
AB  - BACKGROUND & AIMS: An immune-modulating diet (IMD) comprising whey peptides and
      fermented milk products has produced anti-inflammatory effects in various animal
      models and has been employed in peri-operative nutritional care. It was
      investigated the effectiveness of an immune-modulating diet on indomethacin
      induced small-bowel disorders. METHODS: Six-week-old male Sprague-Dawley rats
      were fed a control diet (control group) or an IMD (IMD group) for 14 days.
      Thereafter, they were injected with 10 mg/kg/day indomethacin for 2 consecutive
      days to induce small-bowel disorders. The excretion rate of phenolsulfonphthalein
      in the urine, bacterial translocation (BT) in the mesenteric lymph nodes (MLNs)
      and liver, the number of ulcers that formed in the small bowel, and the
      concentration of cytokines were measured. RESULTS: The IMD group exhibited
      significant suppression of increased permeability of the mucosa and decreased BT
      in the MLNs and liver compared with the control group. The immune-modulating diet
      group also showed a decrease in ulcer formation and lower concentrations of IL-6
      in the ileal tissues compared with the control group. CONCLUSIONS: These data
      suggest that the IMD had a protective effect on the small bowel, and may be
      effective nutritional care in patients with perioperative damage to the small
      intestine and gastrointestinal disorders.

PMID- 24461942
TI  - Evaluation of the durability and antiadhesive action of 2-methacryloyloxyethyl
      phosphorylcholine grafting on an acrylic resin denture base material.
AB  - STATEMENT OF PROBLEM: The polymer 2-methacryloyloxyethyl phosphorylcholine is
      currently used on medical devices to prevent infection. Denture plaque-associated
      infection is regarded as a source of serious dental and medical complications in
      the elderly population, and denture hygiene, therefore, is an issue of
      considerable importance for denture wearers. Furthermore, because denture bases
      are exposed to mechanical stresses, for example, denture brushing, the durability
      of the coating is important for retaining the antiadhesive function of 2
      methacryloyloxyethyl phosphorylcholine. PURPOSE: The purpose of this study is to
      investigate the durability and antiadhesive activity of two 2
      methacryloyloxyethyl phosphorylcholine polymer coating techniques: poly-2
      methacryloyloxyethyl phosphorylcholine grafting and poly-2-methacryloyloxyethyl
      phosphorylcholine-co-n-butyl methacrylate coating. It was revealed that 2
      methacryloyloxyethyl phosphorylcholine polymer coating of the denture base resin
      polymethyl methacrylate decreases bacterial biofilm formation. MATERIAL AND
      METHODS: Durability was examined by rhodamine staining and elemental surface
      analysis and by determining the wetting properties of the 2-methacryloyloxyethyl
      phosphorylcholine polymer-modified polymethyl methacrylate after a friction test
      that comprised 500 brushing cycles. Antiadhesive activity was examined by using a
      Streptococcus mutans biofilm formation assay. RESULTS: Poly-2
      methacryloyloxyethyl phosphorylcholine-grafted polymethyl methacrylate retained 2
      methacryloyloxyethyl phosphorylcholine units and antiadhesive activity even after
      repetitive mechanical stress, whereas co-n-butyl methacrylate-coated polymethyl
      methacrylate did not. CONCLUSION: These results demonstrated that graft
      polymerization of 2-methacryloyloxyethyl phosphorylcholine on denture surfaces
      may contribute to the durability of the coating and prevent microbial retention.

PMID- 24461943
TI  - Postfatigue fracture resistance of modified prefabricated zirconia implant
      abutments.
AB  - STATEMENT OF PROBLEM: The fracture of zirconia abutments has been reported
      relative to different amounts of reduction. Data are not available to demonstrate
      whether the apical vertical reduction of a zirconia abutment at different levels
      can be achieved while maintaining an acceptable load-to-fracture value. PURPOSE:
      The purpose of this study was to evaluate in vitro the effect of different levels
      of preparation of zirconia implant abutments on the fracture load. MATERIAL AND
      METHODS: Twenty-seven zirconia abutments (NobelProcera Abutment Zirconia) and 27
      implant analogs (NobelReplace Implant Replicas) were divided into 3 groups of 9
      abutments and 9 implant analogs. The Zu group (n=9) without any modification and
      with a chamfer margin width of 0.8 mm served as the control. The Zp1 group (n=9)
      was prepared with a chamfer margin width of 0.8 mm and with a 1-mm step in the
      labial margin. The Zp2 group (n=9) was prepared with a chamfer margin width of
      0.8 mm and with a 1.5-mm step in the labial margin. The zirconia abutment was
      attached to the implant analog and fixed in a customized steel mounting table.
      The abutment-implant complex was immersed in saliva substitute to simulate the
      clinical oral environment. A 250 000 cycle sinusoidal fatigue load that ranged
      between 10 N and 210 N was applied to the specimens by using a universal testing
      machine. Subsequently, the specimens were loaded to fracture. One-way ANOVA and
      the Tukey post hoc test were used to compare the groups statistically
      (alpha=.05). RESULTS: The mean (standard deviation) values of the abutment load
      to fracture were as follows: Zu group = 567.3 +/- 35.4 N; Zp1 group = 445.4 +/-
      41.0 N; Zp2 group = 430.5 +/- 39.4 N. The lowest abutment load-to-fracture value
      was in the Zp2 group (408.6 N), whereas the highest abutment load-to-fracture
      value was in the Zu group (591.4 N). A significant (P<.05) difference was found
      between the Zu group and the other groups, but no significant difference was
      found between the Zp1 group and the Zp2 group. The primary mode of fracture (67%)
      was at the abutment-analog interface. CONCLUSION: Preparation of prefabricated
      zirconia abutments had a statistically significant negative effect on the
      abutment load-to-fracture values.

PMID- 24461944
TI  - The 2-implant maxillary overdenture: a clinical report.
AB  - Maxillary implant overdentures present a number of different challenges in
      comparison to the established and predictable benefits of mandibular implant
      overdentures. This report highlights the lack of evidence and conflicting
      findings in the maxillary implant overdenture literature and presents a clinical
      treatment of a 2-implant and subsequently 1-implant maxillary overdenture with
      reduced palatal coverage. 

PMID- 24461945
TI  - Tooth displacement in shortened dental arches: a three-dimensional finite element
      study.
AB  - STATEMENT OF PROBLEM: Some patients may opt for a prosthetic rehabilitation
      without replacing all missing teeth, finishing treatment with a reduced dental
      arch. This choice may be due to biologic reasons or financial restrictions. It is
      unclear if a reduced dental arch functions as well as a complete dental arch.
      PURPOSE: The purpose of this study was to analyze whether shortened dental arches
      could result in tooth displacement. MATERIAL AND METHODS: Four different 3
      dimensional maxillary and mandibular arches with different levels of arch length
      reduction were created. In all models, anatomic structures that represent the
      temporomandibular joint, cortical and cancellous bone, enamel, dentin, and
      periodontal ligament were modeled. Mechanical properties were attributed to each
      anatomic component, and a total occlusal load of 100 N on masseter, temporal, and
      medial pterygoid muscles was simulated for each model. The MSC. Patran software
      was used for the preprocessing and postprocessing of the biomechanical analysis
      of the models. One complete dental arch was used as the control. RESULTS: The
      simulations showed that shortened dental arches presented greater tooth
      displacements than those found in a complete dental arch. The changes in
      mandibular tooth position were greater than those observed in the maxillary
      arches. In finite element models 1 and 2, the largest maxillary displacements
      were found for posterior teeth. CONCLUSIONS: Decreasing numbers of occlusal units
      resulted in increasing amounts of displacements of the remaining teeth, which may
      compromise dental stability in patients with shortened dental arches.

PMID- 24461946
TI  - Fabricating complete dentures with CAD/CAM technology.
AB  - Conventional complete denture prosthetics require several appointments to
      register the maxillomandibular relationship and evaluate the esthetics. The
      fabrication of milled complete dental prostheses with digital scanning technology
      may decrease the number of appointments. The step-by-step method necessary to
      obtain impressions, maxillomandibular relation records, and anterior tooth
      position with an anatomic measuring device is described. The technique allows the
      generation of a virtual denture, which is milled to exact specifications without
      the use of conventional stone casts, flasking, or processing techniques. 

PMID- 24461948
TI  - Fabrication of occlusal rims to record the maxillomandibular relation for
      complete dentures.
AB  - This article describes an alternative method to establish the inclination of the
      occlusal plane by using the hamular notch, incisive papilla plane. By using this
      plane, the fabrication of occlusal rims that conform to an ideal relationship may
      make chairside trimming of the rims more straightforward.

PMID- 24461947
TI  - Comparison of the correlation of photoelasticity and digital imaging to
      characterize the load transfer of implant-supported restorations.
AB  - STATEMENT OF PROBLEM: Whether splinting or not splinting adjacent implants
      together can optimize the stress/strain transfer to the supporting structures
      remains controversial. PURPOSE: The purpose of this study was to compare the
      photoelasticity and digital image correlation (DIC) in analyzing the
      stresses/strains transferred by an implant-supported prosthesis. MATERIAL AND
      METHODS: A polymethylmethacrylate model was made with a combination of acrylic
      resin replicas of a mandibular first premolar and second molar and threaded
      implants replacing the second premolar and first molar. Splinted (G1/G3) and
      nonsplinted (G2/G4) metal-ceramic screw-retained crowns were loaded with (G1/G2)
      and without (G3/G4) the presence of the second molar. Vertical static loads were
      applied to the first molar implant-supported crown (50 N-photoelasticity; 250 N
      DIC). The resulting isochromatic fringes in the photoelastic models were
      photographed, and a single-camera 2-dimensional DIC system recorded the
      deformation at the surface of the resin models. RESULTS: Residual stresses were
      present in the photoelastic model after screw fixation of the crowns. The
      following average photoelastic stress results (MPa) were found around the loaded
      implant: G1 (20.06), G2 (23.49), G3 (30.86), G4 (37.64). Horizontal strains
      (epsilonxx, %) between the molars averaged over the length of the loaded implant
      were found by DIC: G1 (0.08 +/- 0.09), G2 (0.13 +/- 0.10), G3 (0.13 +/- 0.11), G4
      (0.16 +/- 0.11). Splinted crowns transferred lower stresses to the supporting
      bone when the second molar was absent. The second molar optimized the stress
      distribution between the supporting structures even for nonsplinted restorations.
      CONCLUSIONS: Both methods presented similar results and seemed capable of
      indicating where issues associated with stress/strain concentrations might arise.
      However, DIC, while apparently less sensitive than photoelasticity, is not
      restricted to the use of light-polarizing materials.

PMID- 24461949
TI  - Management of excessive movable tissue: a modified impression technique.
AB  - Excessive movable tissue is a challenge in complete denture prosthetics. A
      modified impression technique is presented with polyvinyl siloxane impression
      material and a custom tray with relief areas and perforations in the area of the
      excessive movable tissue. 

PMID- 24461950
TI  - Polymerization time compatibility index of polyvinyl siloxane impression
      materials with conventional and experimental gingival margin displacement agents.
AB  - STATEMENT OF PROBLEM: No consensus exists as to the compatibility of chemical
      agents used with gingival displacement methods with different impression
      materials. PURPOSE: The purpose of this study was to investigate the effect of
      conventional and experimental gingival displacement agents on the polymerization
      time of polyvinyl siloxane impression elastomers. MATERIAL AND METHODS: The study
      comprised 10 gingival displacement agents, including 5 conventional astringents
      (10%, 20%, and 25% aluminum chloride, 25% aluminum sulfate, and 15.5% ferric
      sulfate) and 5 experimental adrenergics (0.1% and 0.01% HCl-epinephrine, 0.05%
      HCl-tetrahydrozoline, 0.05% HCl-oxymetazoline, and 10% HCl-phenylephrine). The
      polymerization time of 240 specimens (weight 3.3 g) of 4 polyvinyl siloxane (PVS)
      impression elastomers, type 3 (Colorise Thermochromic, Hydrorise, Express, and
      Take 1 Advanced), after mixing with 20 MUL of each displacement agent, was
      measured with a viscometer. The 24 specimens from the control group were
      polymerized without contact with the displacement agents. The studies were
      performed at 23 degrees C and 37 degrees C (+/- 0.1 degrees C). RESULTS: A
      polymerization time compatibility index (PTCI) was devised, where the
      polymerization time of PVS mixed with the displacement agents was expressed as
      the percentage of the standard polymerization time of the impression material.
      The PTCI values at 23 degrees C were higher than those at 37 degrees C for both
      groups of displacement agents. At 37 degrees C, the experimental displacement
      agents achieved higher PTCI values than the conventional agents. CONCLUSIONS: All
      of the evaluated displacement agents at laboratory and intraoral temperatures
      induced changes in the polymerization time of PVS. Therefore, chemical
      displacement agents should not come into direct contact with PVS impression
      materials.

PMID- 24461951
TI  - Outcomes in patients with recurrent/progressive glioblastoma treated with
      bevacizumab funded by a regional cancer drug fund.

PMID- 24461952
TI  - Worker evaluation of a macroergonomic intervention in a Brazilian footwear
      company.
AB  - This article presents a macroergonomic intervention in a Brazilian footwear
      company and its evaluation by the workers. Using participatory ergonomics, the
      traditional Taylor/Ford production system was transformed into a socio-technical
      one and tested by 100 volunteers working during 3.5 years in a pilot production
      line. Multiskilling and teamwork were the major changes promoted to enlarge and
      enrich work and make it more flexible. The workers' evaluation pre- and post
      intervention showed an increase in overall satisfaction with the work and more
      commitment to the results and company targets. STATEMENT OF RELEVANCE: This study
      showed that problems and solutions can be identified through participatory
      ergonomics, that it is easier to involve workers than the managerial staff, and
      that a macroergonomic intervention, mainly focusing on work organization, led to
      positive personnel, health and production outcomes, despite management's
      resistance to changes.

PMID- 24461953
TI  - In-house spread sheet based monitor unit verification program for volumetric
      modulated arc therapy.
AB  - Independent monitor unit verification calculation (MUVC) has been recommended by
      several authors for intensity modulated radiotherapy (IMRT) as a patient specific
      quality assurance tool. Aim of the present work is to develop an in-house excel
      spread sheet based MUVC program for volumetric modulated arc therapy (VMAT) using
      Clarkson's integration technique. Total scatter factor (S(c,p)) and tissue
      maximum ratio (TMR) for circular fields obtained from Treatment planning system
      (TPS) were used for the calculation. Multileaf collimator (MLC) interleaf
      leakage, MLC round edge transmission and tongue and groove effect were accounted.
      MUVC calculation was performed for 58 patients both for patient anatomy and for
      homogenous cylindrical phantom. Radiological path lengths were used as water
      equivalent depths (WED) for calculations using patient anatomy. Monitor unit (MU)
      discrepancies between -2.60% and 0.28% with mean deviation of -0.92% +/- 0.75%
      were obtained for homogenous cylindrical phantom calculations. MUVC for patient
      anatomy resulted in large variations between -19.02% and 0.67% for 14 plans where
      isocenter was at a region below -350 HU. But For 44 plans where the isocenter was
      at a region above -350 HU, variations between -3.44% and 0.48% were obtained with
      mean deviation of -1.73% +/- 1.12%. For VMAT patient specific quality assurance,
      the independent MUVC algorithm can be used as an easy and quick auxiliary to
      measurement based verification for plans with isocenter at a region above -350
      HU.

PMID- 24461955
TI  - Syphilis and human experimentation from World War II to the present: a historical
      perspective and reflections on ethics.
AB  - Even after the Nuremberg code was published, research on syphilis often continued
      to fall far short of ethical standards. We review post-World War II research on
      this disease, focusing on the work carried out in Guatemala and Tuskegee. Over a
      thousand adults were deliberately inoculated with infectious material for
      syphilis, chancroid, and gonorrhea between 1946 and 1948 in Guatemala, and
      thousands of serologies were performed in individuals belonging to indigenous
      populations or sheltered in orphanages. The Tuskegee syphilis study, conducted by
      the US Public Health Service, took place between 1932 and 1972 with the aim of
      following the natural history of the disease when left untreated. The subjects
      belonged to a rural black population and the study was not halted when effective
      treatment for syphilis became available in 1945. 

PMID- 24461957
TI  - The interrelations of good welfare indicators assessed in working horses and
      their relationships with the type of work.
AB  - This paper presents a different approach to the welfare of working horses through
      the indicators of good welfare, their interrelations and their relationships with
      the type of work performed by the horses. 697 working horses were assessed by
      using observation, behavioural tests, clinical exams and questionnaires. The
      correlated results highlight the complex and multiple interrelations between the
      good welfare indicators, showing once again that animal welfare is under the
      influence of all its three dimensions (physical and emotional wellbeing and
      naturalness). In working horses, the heavier the work they perform is, the more
      important it is for horse owners/breeders/farmers to fulfil their inherent needs
      so as to help them cope with the multiple specific risks imposed by their work. 

PMID- 24461956
TI  - Genetic characterization of influenza A viruses circulating in pigs and isolated
      in north-east Spain during the period 2006-2007.
AB  - Swine influenza virus is one of the most important pathogens involved in the
      swine respiratory disease complex. Recent serological surveys showed a high
      prevalence of swine influenza strains belonging to the H1N1, H1N2 and H3N2
      subtypes circulating in pigs in Spain. However, little is known about their
      genome sequence. Five swine influenza strains were isolated from some unrelated
      outbreaks occurred during 2006-2007, and their complete genome sequences were
      determined. Phylogenetic analysis revealed that they belonged to the lineages
      "Avian-Like" H1N1, "Human-Like" H3N2, and "Human-Like" H1N2, showing tight
      relationships with early or contemporary strains described in Europe. Notably,
      one virus of the H1N2 subtype showed genetic and antigenic divergence with the
      European contemporary strains or vaccinal strains of the same subtype, suggesting
      that some local and divergent clusters of the virus may pass unnoticed in
      routinary subtyping. Finally, analysis on the entire pattern of genome segments
      suggested that a second reassortment event could have influenced the evolution of
      that divergent H1N2 strain. 

PMID- 24461958
TI  - Primer of statistics in dental research: part I.
AB  - Statistics play essential roles in evidence-based dentistry (EBD) practice and
      research. It ranges widely from formulating scientific questions, designing
      studies, collecting and analyzing data to interpreting, reporting, and presenting
      study findings. Mastering statistical concepts appears to be an unreachable goal
      among many dental researchers in part due to statistical authorities' limitations
      of explaining statistical principles to health researchers without elaborating
      complex mathematical concepts. This series of 2 articles aim to introduce dental
      researchers to 9 essential topics in statistics to conduct EBD with intuitive
      examples. The part I of the series includes the first 5 topics (1) statistical
      graph, (2) how to deal with outliers, (3) p-value and confidence interval, (4)
      testing equivalence, and (5) multiplicity adjustment. Part II will follow to
      cover the remaining topics including (6) selecting the proper statistical tests,
      (7) repeated measures analysis, (8) epidemiological consideration for causal
      association, and (9) analysis of agreement. 

PMID- 24461959
TI  - Properties of a color-changeable chewing gum used to evaluate masticatory
      performance.
AB  - PURPOSE: To clarify the basic properties of a color-changeable chewing gum to
      determine its applicability to evaluations of masticatory performance under
      different types of dental status. METHODS: Ten participants with natural
      dentition aged 26-30 years chewed gum that changes color during several chewing
      strokes over five repetitions. Changes in color were assessed using a
      colorimeter, and then L*, a*, and b* values in the CIELAB color system were
      quantified. Relationships between chewing progression and color changes were
      assessed using regression analysis and the reliability of color changes was
      assessed using intraclass correlation coefficients. We then measured 42 dentate
      participants (age, 22-31 years) and 47 complete denture wearers (age, 44-90
      years) to determine the detectability of masticatory performance under two types
      of dental status. RESULTS: Regression between the number of chewing strokes and
      the difference between two colors was non-linear. The intraclass correlation
      coefficients were highest between 60 and 160 chewing strokes. Dentate and
      edentulous groups significantly differed (Wilcoxon rank sum test) and values were
      widely distributed within each group. CONCLUSIONS: The color of the chewing gum
      changed over a wide range, which was sufficient to evaluate the masticatory
      performance of individuals with natural dentition and those with complete
      dentures. Changes in the color values of the gum reliably reflected masticatory
      performance. These findings indicate that the color-changeable chewing gum will
      be useful for evaluating masticatory performance under any dental status.

PMID- 24461960
TI  - Contrast media induced nephropathy: a literature review of the available evidence
      and recommendations for practice.
AB  - BACKGROUND: Contrast media induced nephropathy (CIN) is a sudden compromise of
      renal function 24-48 h after administering contrast medium during a CT scan or
      angiography. CIN accounts for 10% of hospital acquired renal failure and is
      ranked the third cause of acquiring this condition. Identifying patients at risk
      through proper screening can reduce the occurrence of this condition. PURPOSE:
      This review paper aims to critique current evidence, provide a better
      understanding of CIN, inform nursing practice and make recommendations for
      bedside nurses and future research. METHOD: An integrative review of the
      literature was made using the key terms: "contrast media", "nephritis",
      "nephropathy", "contrast media induced nephropathy scores", "acute kidney
      failure", "acute renal failure" and "acute kidney injury". MeSH key terms used in
      some databases were: "prevention and control", "acute kidney failure" and
      "treatment". Databases searched included Medline, CINAHL and Academic Search
      Complete, and references of relevant articles were also assessed. The search
      included all articles between the years 2000 and 2013. RESULTS: Sixty-seven
      articles were obtained as a result of the search, including RCTs, systematic
      reviews, and retrospective studies. CONCLUSION: Contrast media induced
      nephropathy is an iatrogenic complication occurring secondary to diagnostic or
      therapeutic procedures. At times it is unavoidable but a systematic method of
      risk assessment should be adopted to identify high risk patients for tailored and
      targeted approaches to management interventions. CLINICAL IMPLICATIONS: As the
      use of contrast media is increasing for diagnostic purposes, it is important that
      nurses be aware of the risk factors for CIN, identify and monitor high risk
      patients to prevent deterioration in renal function when possible.

PMID- 24461962
TI  - Trisomy 13 (Patau syndrome) with tetralogy of Fallot--to treat or not to treat?

PMID- 24461964
TI  - Consistency of estimated-origin of representative ventricular premature beats by
      12-lead ambulatory ECG with late-enhancement site in left-ventricle by CMR with
      quantitative volumetric threshold in HCM.

PMID- 24461963
TI  - Trajectories of the Framingham general cardiovascular risk profile in midlife and
      poor motor function later in life: the Whitehall II study.
AB  - BACKGROUND: Vascular risk factors are associated with increased risk of cognitive
      impairment and dementia, but their association with motor function, another key
      feature of aging, has received little research attention. We examined the
      association between trajectories of the Framingham general cardiovascular disease
      risk score (FRS) over midlife and motor function later in life. METHODS: A total
      of 5376 participants of the Whitehall II cohort study (29% women) who had up to
      four repeat measures of FRS between 1991-1993 (mean age=48.6 years) and 2007-2009
      (mean age=65.4 years) and without history of stroke or coronary heart disease in
      2007-2009 were included. Motor function was assessed in 2007-2009 through
      objective tests (walking speed, chair rises, balance, finger tapping, grip
      strength). We used age- and sex-adjusted linear mixed models. RESULTS:
      Participants with poorer performances for walking speed, chair rises, and balance
      in 2007-2009 had higher FRS concurrently and also in 1991-1993, on average 16
      years earlier. These associations were robust to adjustment for cognition, socio
      economic status, height, and BMI, and not explained by incident mobility
      limitation prior to motor assessment. No association was found with finger
      tapping and grip strength. CONCLUSIONS: Cardiovascular risk early in midlife is
      associated with poor motor performances later in life. Vascular risk factors play
      an important and under-recognized role in motor function, independently of their
      impact on cognition, and suggest that better control of vascular risk factors in
      midlife may prevent physical impairment and disability in the elderly.

PMID- 24461965
TI  - Syncope in a patient with a large left ventricular hydatid cyst: an unusual
      presentation.

PMID- 24461961
TI  - Use of drug treatment for secondary prevention of cardiovascular disease in urban
      and rural communities of China: China Kadoorie Biobank Study of 0.5 million
      people.
AB  - AIMS: Relatively little is known about the use of medication for the secondary
      prevention of cardiovascular disease (CVD) events in China, and the relevance to
      it of socioeconomic, lifestyle and health-related factors. METHODS AND RESULTS:
      We analysed cross-sectional data from the China Kadoorie Biobank (CKB) of 512,891
      adults aged 30-79 years recruited from 1737 rural and urban communities in China.
      Information about doctor-diagnosed ischaemic heart disease (IHD) and stroke, and
      the use of medication for the secondary prevention of CVD events, were recorded
      by interview. Multivariate logistic regression was used to estimate odds ratios
      (ORs) for use of secondary preventive treatment, adjusting simultaneously for
      age, sex, area and education. Overall, 23,129 (4.5%) participants reported a
      history of CVD (3.0% IHD, 1.7% stroke). Among them, 35% reported current use of
      any of 6 classes of drug (anti-platelet, statins, diuretics, ACE-I, beta-blockers
      or calcium-channel blockers) for the prevention of CVD events, with the rate of
      usage greater in those with older age, higher levels of income, education, BMI or
      blood pressure. The use of these agents was associated positively with history of
      diagnosed hypertension (OR 7.5; 95% confidence intervals: 7.08-8.06) and diabetes
      (1.40; 1.28-1.52) and inversely with self-rated health status, but there was no
      association with years since diagnosis. CONCLUSIONS: Despite recent improvements
      in hospital care in China, only one in three individuals with prior CVD was
      routinely treated with any proven secondary preventive drugs. The treatment rates
      were correlated with the existence of other risk factors, in particular evidence
      of hypertension.

PMID- 24461966
TI  - Takotsubo cardiomyopathy presenting as S-T elevation myocardial infarction: not
      gone but forgotten?

PMID- 24461967
TI  - Combination use of ranolazine with dofetilide for the maintenance of atrial
      fibrillation.

PMID- 24461968
TI  - Hypoplastic left coronary artery with large collateral vessels from an ectatic
      right coronary artery: multimodality imaging-based diagnostic work-up.

PMID- 24461969
TI  - Left ventricular diastolic wall strain and myocardial fibrosis in treated
      hypertension.

PMID- 24461970
TI  - Retrograde coronary venous infusion provides targeted cell engraftment into
      infarcted myocardium.

PMID- 24461971
TI  - Admission levels of circulating miR-499-5p and risk of death in elderly patients
      after acute non-ST elevation myocardial infarction.

PMID- 24461972
TI  - Patent foramen ovale, transient ischemic attack and Kounis syndrome.

PMID- 24461973
TI  - Outcomes with short-term versus long-term antiplatelet dual therapy after drug
      eluting stenting: quantifying the equivalence margins.

PMID- 24461974
TI  - In the era of beta-blockers better is the VE/VCO2 slope for heart transplant
      selection in patients with systolic heart failure.

PMID- 24461975
TI  - Evidence from the Resorbable-polymer stent versus Unresorbable-polymer stent
      Deployment for coronary Intervention: (RUDI-2) registry.

PMID- 24461976
TI  - Microaneurysm formation in an intercostal artery--a possible mechanism for
      intramural hematoma of the distal thoracic aorta.

PMID- 24461977
TI  - Beyond age, the need for useful parameters to identify heart failure patients in
      sinus rhythm that can benefit from oral anticoagulation.

PMID- 24461978
TI  - The CHA2DS2-VASc score predicts 320-slice CT-based coronary artery plaques and
      >50% stenosis in subjects with chronic and paroxysmal atrial fibrillation.

PMID- 24461980
TI  - Screening of depression in cardiac patients: is the HADS an effective tool?

PMID- 24461979
TI  - Comparison of low and high dose intracoronary adenosine and acetylcholine in
      women undergoing coronary reactivity testing: results from the NHLBI-sponsored
      Women's Ischemia Syndrome Evaluation (WISE).

PMID- 24461981
TI  - Preterm birth is associated with risk of essential hypertension in later life.

PMID- 24461982
TI  - Utility of Framingham general cardiovascular disease risk score for predicting 10
      year cardiovascular risk in an Inner Mongolian population: a prospective cohort
      study.

PMID- 24461984
TI  - Non-standard dose dronedarone in treating atrial fibrillation patients.

PMID- 24461985
TI  - Pseudoresistant hypertension due to poor medication adherence.

PMID- 24461983
TI  - Acute multivessel revascularization improves 1-year outcome in ST-elevation
      myocardial infarction: a nationwide study cohort from the AMIS Plus registry.
AB  - BACKGROUND: The optimal strategy for percutaneous coronary intervention (PCI) of
      ST-segment elevation myocardial infarction (STEMI) in multi-vessel disease (MVD),
      i.e., multi-vessel PCI (MV-PCI) vs. PCI of the infarct-related artery only (IRA
      PCI), still remains unknown. METHODS: Patients of the AMIS Plus registry admitted
      with an acute coronary syndrome were contacted after a median of 378 days
      (interquartile range 371-409). The primary end-point was all-cause death. The
      secondary end-point included all major adverse cardiovascular and cerebrovascular
      events (MACCE) including death, re-infarction, re-hospitalization for cardiac
      causes, any cardiac re-intervention, and stroke. RESULTS: Between 2005 and 2012,
      8330 STEMI patients were identified, of whom 1909 (24%) had MVD. Of these, 442
      (23%) received MV-PCI and 1467 (77%) IRA-PCI. While all-cause mortality was
      similar in both groups (2.7% both, p>0.99), MACCE was significantly lower after
      MV-PCI vs. IRA-PCI (15.6% vs. 20.0%, p=0.038), mainly driven by lower rates of
      cardiac re-hospitalization and cardiac re-intervention. Patients undergoing MV
      PCI with drug-eluting stents had lower rates of all-cause mortality (2.1% vs.
      7.4%, p=0.026) and MACCE (14.1% vs. 25.9%, p=0.042) compared with those receiving
      bare metal stents (BMS). In multivariate analysis, MV-PCI (odds ratio, OR 0.69,
      95% CI 0.51-0.93, p=0.017) and comorbidities (Charlson index >= 2; OR 1.42, 95%
      CI 1.05-1.92, p=0.025) were independent predictors for 1-year MACCE. CONCLUSION:
      In an unselected nationwide real-world cohort, an approach using immediate
      complete revascularization may be beneficial in STEMI patients with MVD regarding
      MACCE, specifically when drug-eluting stents are used, but not regarding
      mortality. This has to be tested in a randomized controlled trial.

PMID- 24461986
TI  - Aspiration of intact coronary bifurcation thrombus in ST-elevation myocardial
      infarction.

PMID- 24461987
TI  - Necessity for rule out coronary artery disease with the positive findings of 18F
      FDG-PET in case of systemic sarcoidosis.

PMID- 24461988
TI  - Muscle strength of male inpatients with heart failure with reduced versus
      preserved ejection fraction.

PMID- 24461989
TI  - Is there a link between Takotsubo syndrome and some cases of nonischemic
      cardiomyopathy? A proposal of an animal model.

PMID- 24461990
TI  - Identification of serum microRNAs for cardiovascular risk stratification in
      dyslipidemia subjects.

PMID- 24461991
TI  - Reply to comment on: idiopathic pericarditis presenting large hemorrhagic
      pericardial effusion by Dr. George A Lazaros.

PMID- 24461992
TI  - Predictors of mortality in acute heart failure and severe renal dysfunction. Does
      formula for glomerular filtration rate have any impact? Data from IN-HF outcome
      registry.

PMID- 24461993
TI  - A novel approach for the diagnosis of ventricular tachycardia based on phase
      space reconstruction of ECG.

PMID- 24461994
TI  - Pharmacological cardioprotection in the acute myocardial infarction: potential of
      beta-blockers and melatonin as forgotten cardioprotective agents.

PMID- 24461995
TI  - A comparative study of the mini-punch grafting and hair follicle transplantation
      in the treatment of refractory and stable vitiligo.
AB  - BACKGROUND: Some vitiligo lesions are resistant to all medical treatments.
      OBJECTIVE: We sought to compare the efficacy of hair follicle transplantation and
      mini-punch grafting for the treatment of refractory vitiligo lesions. METHODS: A
      total of 25 patients with stable and resistant vitiligo participated in the
      study. In each patient, a resistant vitiligo patch was divided into 2 equal
      parts. One part was treated with hair follicle transplantation and the other part
      with mini-punch grafting. Postsurgically, the recipient areas were exposed to
      narrowband ultraviolet B twice a week for 6 months. The diameter of the
      repigmentation around each graft was measured monthly. RESULTS: At the end of the
      sixth month, 68% of follicle grafts, and 72% of mini-punch grafts, had
      repigmentation. The mean diameter of repigmentation around follicle grafts was 5
      +/- 1.7 mm and around punch grafts was 5.3 +/- 1.6 mm. There was no significant
      difference between the 2 groups statistically (P = .18). LIMITATIONS: Small
      sample size and short time of follow-up are limitations. CONCLUSIONS: Because the
      results of the 2 methods are not statistically different and mini-punch grafting
      is much easier to do than follicular transplantation, we recommend mini-punch
      grafting to treat drug-resistant vitiligo.

PMID- 24461996
TI  - Normal sizes of internal jugular veins in children/adolescents aged birth to 18
      years at rest and during the Valsalva maneuver.
AB  - OBJECTIVES: We aimed to establish normal ultrasonographic (US) values of internal
      jugular vein (IJV) sizes in children/adolescents aged birth to 18 years and to
      determine the correlation of US measurements with age, height, weight and body
      surface area (BSA) of children in different age groups. METHODS: Two hundred and
      thirty-six healthy children (0-18 years) were divided into four groups according
      to their age (0-2, 3-6, 7-12, and 13-18 years). US measurements (transverse,
      anteroposterior diameter, and cross-sectional area at rest and during the
      Valsalva maneuver) of bilateral IJVs were taken at the level of cricoid
      cartilage. RESULTS: Our study gives information about the reference values in
      children between birth to 18 years of age. There were significant differences
      between measurements taken at rest and during the Valsalva maneuver in all age
      groups. Moderate to strong correlations (clinically significant) between age,
      height and BSA of the subjects and IJV measurements were detected only in the 0-2
      years age group. The strength of the correlations decreased with increasing age.
      Pearson's correlation revealed that height had the strongest and weight had the
      weakest correlation with US measurements. 'Height' was an independent variable on
      the right, and 'age' on the left side, except for rest CSA, when a regression
      analysis was performed for clinically significant correlations. CONCLUSIONS:
      Determination of normal reference values for US measurements of the IJV and
      knowledge of correlation with age, height, weight and BSA might be valuable
      during interventional procedures and for the diagnosis of phlebectasia in
      children/adolescents.

PMID- 24461997
TI  - Capecitabine plus irinotecan versus 5-FU/leucovorin plus irinotecan in the
      treatment of colorectal cancer: a meta-analysis.
AB  - BACKGROUND: The XELIRI regimen and FOLFIRI regimen are used as the first-line
      treatment of metastatic colorectal cancer. A comparison of findings from
      different studies that examined the efficacy and safety of these 2 regimens often
      show conflicting results. This metaanalysis compared the XELIRI and FOLFIRI
      regimens in the treatment of mCRC. PATIENTS AND METHODS: Six studies comparing
      the safety and efficacy of XELIRI- and FOLFIRI-based treatment of mCRC were
      identified from MEDLINE, Cochrane, EMBASE, and Google Scholar (until January 31,
      2013) databases. RESULTS: No significant difference in ORR, PFS, or OS between
      XELIRI and FOLFIRI as first-line therapy in patients with colorectal cancer was
      found in this analysis. Except for XELIRI being associated with a higher
      incidence of diarrhea, both treatment regimens had similar safety profiles.
      CONCLUSION: Both XELIRI and FOLFIRI regimens had similar efficacy as first-line
      treatment in patients with mCRC with similar adverse event profiles. Our findings
      suggest that XELIRI and FOLFIRI are appropriate first-line treatment options for
      mCRC patients.

PMID- 24461998
TI  - Entrainment of brain oscillations by transcranial alternating current
      stimulation.
AB  - Novel methods for neuronal entrainment [1-4] provide the unique opportunity to
      modulate perceptually relevant brain oscillations [5, 6] in a frequency-specific
      manner and to study their functional impact on distinct cognitive functions.
      Recently, evidence has emerged that tACS (transcranial alternating current
      stimulation) can modulate cortical oscillations [7-9]. However, the study of
      electrophysiological effects has been hampered so far by the absence of
      concurrent electroencephalogram (EEG) recordings. Here, we applied 10 Hz tACS to
      the parieto-occipital cortex and utilized simultaneous EEG recordings to study
      neuronal entrainment during stimulation. We pioneer a novel approach for
      simultaneous tACS-EEG recordings and successfully separate stimulation artifacts
      from ongoing and event-related cortical activity. Our results reveal that 10 Hz
      tACS increases parieto-occipital alpha activity and synchronizes cortical
      oscillators with similar intrinsic frequencies to the entrainment frequency.
      Additionally, we demonstrate that tACS modulates target detection performance in
      a phase-dependent fashion highlighting the causal role of alpha oscillations for
      visual perception. 

PMID- 24461999
TI  - Nanog is dispensable for the generation of induced pluripotent stem cells.
AB  - Cellular reprogramming from somatic cells to induced pluripotent stem cells
      (iPSCs) can be achieved through forced expression of the transcription factors
      Oct4, Klf4, Sox2, and c-Myc (OKSM) [1-4]. These factors, in combination with
      environmental cues, induce a stable intrinsic pluripotency network that confers
      indefinite self-renewal capacity on iPSCs. In addition to Oct4 and Sox2, the
      homeodomain-containing transcription factor Nanog is an integral part of the
      pluripotency network [5-11]. Although Nanog expression is not required for the
      maintenance of pluripotent stem cells, it has been reported to be essential for
      the establishment of both embryonic stem cells (ESCs) from blastocysts and iPSCs
      from somatic cells [10, 12]. Here we revisit the role of Nanog in direct
      reprogramming. Surprisingly, we find that Nanog is dispensable for iPSC formation
      under optimized culture conditions. We further document that Nanog-deficient
      iPSCs are transcriptionally highly similar to wild-type iPSCs and support the
      generation of teratomas and chimeric mice. Lastly, we provide evidence that the
      presence of ascorbic acid in the culture media is critical for overcoming the
      previously observed reprogramming block of Nanog knockout cells. 

PMID- 24462000
TI  - Mechanical and geometrical constraints control kinesin-based microtubule
      guidance.
AB  - Proper organization of microtubule networks depends on microtubule-associated
      proteins and motors that use different spatial cues to guide microtubule growth
      [1-3]. For example, it has been proposed that the uniform minus-end-out
      microtubule organization in dendrites of Drosophila neurons is maintained by
      steering of polymerizing microtubules along the stable ones by kinesin-2 motors
      bound to growing microtubule plus ends [4]. To explore the mechanics of kinesin
      guided microtubule growth, we reconstituted this process in vitro. In the
      presence of microtubule plus-end tracking EB proteins, a constitutively active
      kinesin linked to the EB-interacting motif SxIP effectively guided polymerizing
      microtubules along other microtubules both in cells and in vitro. Experiments
      combined with modeling revealed that at angles larger than 90 degrees , guidance
      efficiency is determined by the force needed for microtubule bending. At angles
      smaller than 90 degrees , guidance requires microtubule growth, and guidance
      efficiency depends on the ability of kinesins to maintain contact between the two
      microtubules despite the geometrical constraints imposed by microtubule length
      and growth rate. Our findings provide a conceptual framework for understanding
      microtubule guidance during the generation of different types of microtubule
      arrays. 

PMID- 24462001
TI  - NANOG amplifies STAT3 activation and they synergistically induce the naive
      pluripotent program.
AB  - Reprogramming of a differentiated cell back to a naive pluripotent identity is
      thought to occur by several independent mechanisms. Two such mechanisms include
      NANOG and activated STAT3 (pSTAT3), known master regulators of naive pluripotency
      acquisition [1-5]. Here, we investigated the relationship between NANOG and
      pSTAT3 during the establishment and maintenance of naive pluripotency.
      Surprisingly, we found that NANOG enhances LIF signal transduction, resulting in
      elevated pSTAT3. This is mediated, at least in part, by suppression of the
      expression of the LIF/STAT3 negative regulator SOCS3. We also discovered NANOG to
      be limiting for the expression of KLF4, a canonical "Yamanaka" reprogramming
      factor [6] and key pSTAT3 target [2, 7, 8]. KLF4 expression resulted from the
      codependent and synergistic action of NANOG and pSTAT3 in embryonic stem cells
      and during initiation of reprogramming. Additionally, within 48 hr, the combined
      actions of NANOG and pSTAT3 in a reprogramming context resulted in reactivation
      of genes associated with naive pluripotency. Importantly, we show that NANOG can
      be bypassed during reprogramming by exogenous provision of its downstream
      effectors, namely pSTAT3 elevation and KLF4 expression. In conclusion, we propose
      that mechanisms of reprogramming are linked, rather than independent, and are
      centered on a small number of genes, including NANOG. 

PMID- 24462002
TI  - Timing of single-neuron and local field potential responses in the human medial
      temporal lobe.
AB  - The relationship between the firing of single cells and local field potentials
      (LFPs) has received increasing attention, with studies in animals [1-11] and
      humans [12-14]. Recordings in the human medial temporal lobe (MTL) have
      demonstrated the existence of neurons with selective and invariant responses
      [15], with a relatively late but precise response onset around 300 ms after
      stimulus presentation [16-18] and firing only upon conscious recognition of the
      stimulus [19]. This represents a much later onset than expected from direct
      projections from inferotemporal cortex [16, 18]. The neural mechanisms underlying
      this onset remain unclear. To address this issue, we performed a joint analysis
      of single-cell and LFP responses during a visual recognition task. Single-neuron
      responses were preceded by a global LFP deflection in the theta range. In
      addition, there was a local and stimulus-specific increase in the single-trial
      gamma power. These LFP responses correlated with conscious recognition. The
      timing of the neurons' firing was phase locked to these LFP responses. We propose
      that whereas the gamma phase locking reflects the activation of local networks
      encoding particular recognized stimuli, the theta phase locking reflects a global
      activation that provides a temporal window for processing consciously perceived
      stimuli in the MTL.

PMID- 24462003
TI  - Canopy flow analysis reveals the advantage of size in the oldest communities of
      multicellular eukaryotes.
AB  - VIDEO ABSTRACT: At Mistaken Point, Newfoundland, Canada, rangeomorph "fronds"
      dominate the earliest (579-565 million years ago) fossil communities of large
      (0.1 to 2 m height) multicellular benthic eukaryotes. They lived in low-flow
      environments, fueled by uptake [1-3] of dissolved reactants (osmotrophy).
      However, prokaryotes are effective osmotrophs, and the advantage of taller
      eukaryotic osmotrophs in this deep-water community context has not been
      addressed. We reconstructed flow-velocity profiles and vertical mixing using
      canopy flow models appropriate to the densities of the observed communities.
      Further modeling of processes at organismal surfaces documents increasing uptake
      with height in the community as a function of thinning of the diffusive boundary
      layer with increased velocity. The velocity profile, produced by canopy flow in
      the community, generates this advantage of upward growth. Alternative models of
      upward growth advantage based on redox/resource gradients fail, given the
      efficiency of vertical mixing. In benthic communities of osmotrophs of sufficient
      density, access to flow in low-flow settings provides an advantage to taller
      architecture, providing a selectional driver for communities of tall eukaryotes
      in contexts where phototropism cannot contribute to upward growth. These
      Ediacaran deep-sea fossils were preserved during the increasing oxygenation prior
      to the Cambrian radiation of animals and likely represent an important phase in
      the ecological and evolutionary transition to more complex eukaryotic forms.

PMID- 24462004
TI  - An EB1-kinesin complex is sufficient to steer microtubule growth in vitro.
AB  - Proper microtubule polarity underlies overall neuronal polarity, but mechanisms
      for maintaining microtubule polarity are not well understood. Previous live
      imaging in Drosophila dendritic arborization neurons showed that while
      microtubules are uniformly plus-end out in axons, dendrites possess uniformly
      minus-end-out microtubules [1]. Thus, maintaining uniform microtubule polarity in
      dendrites requires that growing microtubule plus ends entering branch points be
      actively directed toward the cell body. A model was proposed in which EB1 tracks
      the plus ends of microtubules growing into a branch and an associated kinesin-2
      motor walks along a static microtubule to steer the plus end toward the cell
      body. However, the fast plus-end binding dynamics of EB1 [2-5] appear to be at
      odds with this proposed mechanical function. To test this model in vitro, we
      reconstituted the system by artificially dimerizing EB1 to kinesin, growing
      microtubules from immobilized seeds, and imaging encounters between growing
      microtubule plus ends and static microtubules. Consistent with in vivo
      observations, the EB1-kinesin complex actively steered growing microtubules.
      Thus, EB1 kinetics and mechanics are sufficient to bend microtubules for several
      seconds. Other kinesins also demonstrated this activity, suggesting this is a
      general mechanism for organizing and maintaining proper microtubule polarity in
      cells. 

PMID- 24462005
TI  - Histopathologic and immunohistochemical sequelae of bariatric embolization in a
      porcine model.
AB  - PURPOSE: To evaluate the histopathologic sequelae of bariatric embolization on
      the gastric mucosa and to correlate with immunohistochemical evaluation of the
      gastric fundus, antrum, and duodenum. MATERIALS AND METHODS: This study was
      performed on 12 swine stomach and duodenum specimens after necropsy. Of the 12
      swine, 6 had previously undergone bariatric embolization of the gastric fundus,
      and the 6 control swine had undergone a sham procedure with saline. Gross
      pathologic, histopathologic, and immunohistochemical examinations of the stomach
      and duodenum were performed. Specifically, mucosal integrity, fibrosis, ghrelin
      expressing cells, and gastrin-expressing cells were assessed. RESULTS: Gross and
      histopathologic evaluation of treatment animals showed healing or healed mucosal
      ulcers in 50% of animals, with gastritis in 100% of treatment animals and in five
      of six control animals. The ghrelin-immunoreactive mean cell density was
      significantly lower in the gastric fundus in the treated animals compared with
      control animals (15.3 vs 22.0, P < .01) but similar in the gastric antrum (9.3 vs
      14.3, P = .08) and duodenum (8.5 vs 8.6, P = .89). The gastrin-expressing cell
      density was significantly lower in the antrum of treated animals compared with
      control animals (82.2 vs 126.4, P = .03). A trend toward increased fibrosis was
      suggested in the gastric fundus of treated animals compared with controls (P =
      .07). CONCLUSIONS: Bariatric embolization resulted in a significant reduction in
      ghrelin-expressing cells in the gastric fundus without evidence of upregulation
      of ghrelin-expressing cells in the duodenum. Healing ulcerations in half of
      treated animals underscores the need for additional refinement of this procedure.

PMID- 24462006
TI  - Calculation of operating expenses for conventional transarterial
      chemoembolization in an academic medical center: a step toward defining the value
      of transarterial chemoembolization.
AB  - PURPOSE: To determine the "real cost" of conventional transarterial
      chemoembolization in the treatment of patients with unresectable hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Comprehensive cost data for performance
      of conventional transarterial chemoembolization were calculated from a
      retrospective review of records of 50 consecutive outpatient transarterial
      chemoembolization procedures in 36 patients with HCC. Costs included labor,
      equipment, facility acquisition and maintenance, overhead, and administrative
      costs in a single academic medical center. Hourly rate operational costs for the
      angiography suite and recovery area were calculated, to which the consumable
      supply costs were added. Conventional transarterial chemoembolization was defined
      as selective intrahepatic administration of chemotherapeutic agents (doxorubicin
      and mitomycin C) emulsified in ethiodized oil (Lipiodol). RESULTS: The hourly
      rate to operate an angiography suite at the institution was calculated to be
      $539/h. Recovery time was calculated at $108/h. Median overall cost of
      conventional transarterial chemoembolization was $3,269 (range, $2,223-$5,654).
      This overall cost comprised median room and personnel costs of $763 (range, $404
      $1,797), consumable costs of $1,886 (range, $1,134-$4,126), and recovery costs of
      $378 (range, $162-$864). CONCLUSIONS: The largest contribution (62%) to the real
      cost of outpatient transarterial chemoembolization comes from the expendable
      equipment used in the procedure. The angiography suite and personnel costs
      constitute 25% of the total, and recovery costs constitute 13%. This finding is a
      change from previous reports in which angiography suite operation was the
      greatest contributor to cost. Understanding real cost is an essential step in
      determining the value of the procedure.

PMID- 24462007
TI  - Intersection of the stringent response and the CodY regulon in low GC Gram
      positive bacteria.
AB  - Bacteria adapt efficiently to a wide range of nutritional environments.
      Therefore, they possess overlapping regulatory systems that detect intracellular
      pools of key metabolites. In low GC Gram-positive bacteria, two global
      regulators, the stringent response and the CodY repressor, respond to an
      intracellular decrease in amino acid content. Amino acid limitation leads to
      rapid synthesis of the alarmones pppGpp and ppGpp through the stringent response
      and inactivates the CodY repressor. Two cofactors, branched chain amino acids
      (BCAA) and GTP, are ligands for CodY and facilitate binding to the target DNA.
      Because (p)ppGpp synthesis and accumulation evidentially reduce the intracellular
      GTP pool, CodY is released from the DNA, and transcription of target genes is
      altered. Here, we focus on this intimate link between the stringent response and
      CodY regulation in different Gram-positive species. 

PMID- 24462008
TI  - Secretion and activation of the Serratia marcescens hemolysin by structurally
      defined ShlB mutants.
AB  - The ShlA hemolysin of Serratia marcescens is secreted across the outer membrane
      by the ShlB protein; ShlB belongs to the two-partner secretion system (type Vb),
      a subfamily of the Omp85 outer membrane protein assembly and secretion
      superfamily. During secretion, ShlA is converted from an inactive non-hemolytic
      form into an active hemolytic form. The structure of ShlB is predicted to consist
      of the N-terminal alpha-helix H1, followed by the two polypeptide-transport
      associated domains POTRA P1 and P2, and the beta-barrel of 16 beta-strands. H1 is
      inserted into the pore of the beta-barrel in the outer membrane; P1 and P2 are
      located in the periplasm. To obtain insights into the secretion and activation of
      ShlA by ShlB, we isolated ShlB mutants impaired in secretion and/or activation.
      The triple H1 P1 P2 mutant did not secrete ShlA. The P1 and P2 deletion
      derivatives secreted reduced amounts of ShlA, of which P1 showed some hemolysis,
      whereas P2 was inactive. Deletion of loop 6 (L6), which is conserved among
      exporters of the Omp85 family, compromised activation but retained low secretion.
      Secretion-negative mutants generated by random mutagenesis were located in loop
      6. The inactive secreted ShlA derivatives were complemented in vitro to active
      ShlA by an N-terminal ShlA fragment (ShlA242) secreted by ShlB. Deletion of H1
      did not impair secretion of hemolytic ShlA. The study defines domains of ShlB
      which are important for ShlA secretion and activation. 

PMID- 24462009
TI  - Immune control of Staphylococcus aureus - regulation and counter-regulation of
      the adaptive immune response.
AB  - Successful vaccination relies on immune memory, a core competence of the adaptive
      immune system. This review summarizes the current knowledge about the adaptive
      immune response to Staphylococcus aureus as well as the bacterial escape
      mechanisms. The Janus-faced bacteria, both life-threatening pathogens and
      peaceful cohabitants of their human host, have so far frustrated all attempts at
      vaccine development. This begs the question of whether the adaptive immune system
      is at all able to protect against S. aureus infection. In search of an answer the
      main functions of the adaptive immune system are probed for potential mechanisms
      of protection against S. aureus, which may be put to the test in future research.

PMID- 24462010
TI  - My recent reading list of nonmedical books.

PMID- 24462011
TI  - Diagnostic and therapeutic implications of type 2 myocardial infarction: review
      and commentary.
AB  - The Task Force for the Universal Definition of Myocardial Infarction recently
      published updated guidelines for the clinical and research diagnosis of
      myocardial infarction under a variety of circumstances and in a variety of
      categories. A type 1 myocardial infarction (MI) is usually the result of
      atherosclerotic coronary artery disease with thrombotic coronary arterial
      obstruction secondary to atherosclerotic plaque rupture, ulceration, fissuring,
      or dissection, causing coronary arterial obstruction with resultant myocardial
      ischemia and necrosis. Patients with a type 2 MI do not have atherosclerotic
      plaque rupture. In this latter group of patients, myocardial necrosis occurs
      because of an increase in myocardial oxygen demand or a decrease in myocardial
      blood flow. Type 2 MI has been the subject of considerable clinical discussion
      and confusion. This review by knowledgeable members of the Task Force seeks to
      help clinicians resolve the confusion surrounding type 2 MI. 

PMID- 24462012
TI  - Can group medical clinics improve lipid management in diabetes?
AB  - BACKGROUND: Group medical clinics may improve diabetes and hypertension control,
      but data about dyslipidemia are limited. We examined the impact of group medical
      clinics on lipids among patients with uncontrolled diabetes and hypertension.
      METHODS: Prespecified secondary analysis of 239 veterans randomized to group
      medical clinics or usual care. Lipids were assessed at study baseline, midpoint,
      and end. We used linear mixed models to compare lipid levels between arms and
      generalized estimating equation models to compare low-density lipoprotein
      cholesterol (LDL-C) goal attainment. An additional post hoc analysis examined
      intensification of cholesterol-lowering medications in both arms. RESULTS: At
      baseline, mean total cholesterol was 169.7 mg/dL (SD 47.8), LDL-C 98.2 mg/dL (SD
      41.7), and high-density lipoprotein cholesterol (HDL-C) 39.3 mg/dL (SD 13.0).
      Median baseline triglycerides were 131 mg/dL (interquartile range 122). By study
      end, mean total cholesterol and LDL-C in group medical clinics were 14.2 mg/dL (P
      = .01) and 9.2 mg/dL (P = .02) lower than usual care, respectively; 76% of group
      medical clinic patients met goals for LDL-C, versus 61% of usual care patients (P
      = .02). Triglycerides and HDL-C remained similar between study arms. Treatment
      intensification occurred in 52% of group medical clinic patients, versus 37% of
      usual care patients between study baseline and end (P = .04). The mean statin
      dose was higher in group medical clinic patients at study midpoint and end.
      CONCLUSIONS: Group medical clinics appear to enhance lipid management among
      patients with diabetes and hypertension. This may be a result of greater
      intensification of cholesterol-lowering medications in group medical clinics
      relative to usual care.

PMID- 24462013
TI  - Identification of cardiometabolic risk: visceral adiposity index versus
      triglyceride/HDL cholesterol ratio.
AB  - BACKGROUND: The plasma concentration ratio of triglyceride (TG)/high-density
      lipoprotein cholesterol (HDL-C) can identify cardiometabolic risk and
      cardiovascular disease. The visceral adiposity index is a sex-specific index, in
      which measurements of body mass index and waist circumference are combined with
      TG and HDL-C concentrations. The current analysis was initiated to see if the
      visceral adiposity index would improve the ability of the TG/HDL-C to identify
      increased cardiometabolic risk and outcome. METHODS: Cardiometabolic data were
      obtained in 2003 from 926 apparently healthy individuals, 796 of whom were
      evaluated in 2012 for evidence of incident cardiovascular disease. The
      relationship between TG/HDL-C and values for visceral adiposity index was
      evaluated by Pearson's correlation coefficient. The relative risks for first
      cardiovascular event between individuals above and below the TG/HDL-C sex
      specific cut points, and in the top quartile of visceral adiposity index versus
      the remaining 3 quartiles, were estimated using Cox proportional hazard models.
      RESULTS: TG/HDL-C concentration and visceral adiposity index were highly
      correlated (r = 0.99) in both men and women. Although more men (133 vs121) and
      women (73 vs 59) were identified as being at "high risk" by an elevated TG/HDL-C
      ratio, the individual cardiometabolic risk factors were essentially identical
      with either index used. However, the hazard ratio of developing cardiovascular
      disease was significantly increased in individuals with an elevated TG/HDL-C,
      whereas it was not the case when the visceral adiposity index was used to define
      "high risk." CONCLUSION: The visceral adiposity index does not identify
      individuals with an adverse cardiometabolic profile any better than the TG/HDL-C.

PMID- 24462014
TI  - The reply.

PMID- 24462015
TI  - Does hypomagnesemia predict faster progression of nondiabetic chronic kidney
      disease?

PMID- 24462016
TI  - The reply.

PMID- 24462017
TI  - Electrocardiographic STEMI: a common but nonspecific finding in the ICU.

PMID- 24462018
TI  - Ongoing discussion about the US clinical Lyme trials.

PMID- 24462019
TI  - Potential benefits of retreatment highlight the need for additional Lyme disease
      research.

PMID- 24462020
TI  - Alkaline phosphatase: a possible treatment for sepsis-associated acute kidney
      injury in critically ill patients.
AB  - Acute kidney injury (AKI) is a common disease in the intensive care unit and
      accounts for high morbidity and mortality. Sepsis, the predominant cause of AKI
      in this setting, involves a complex pathogenesis in which renal inflammation and
      hypoxia are believed to play an important role. A new therapy should be aimed at
      targeting both these processes, and the enzyme alkaline phosphatase, with its
      dual mode of action, might be a promising candidate. First, alkaline phosphatase
      is able to reduce inflammation through dephosphorylation and thereby
      detoxification of endotoxin (lipopolysaccharide), which is an important mediator
      of sepsis. Second, adenosine triphosphate, released during cellular stress caused
      by inflammation and hypoxia, has detrimental effects but can be converted by
      alkaline phosphatase into adenosine with anti-inflammatory and tissue-protective
      effects. These postulated beneficial effects of alkaline phosphatase have been
      confirmed in animal experiments and two phase 2a clinical trials showing that
      kidney function improved in critically ill patients with sepsis-associated AKI.
      Because renal inflammation and hypoxia also are observed commonly in AKI induced
      by other causes, it would be of interest to investigate the therapeutic effect of
      alkaline phosphatase in these nephropathies as well. 

PMID- 24462021
TI  - The globalization of the nursing workforce: Pulling the pieces together.
AB  - The "globalization" of health care creates an increasingly interconnected
      workforce spanning international boundaries, systems, structures, and processes
      to provide care to and improve the health of peoples around the world. Because
      nurses comprise a large sector of the global health workforce, they are called
      upon to provide a significant portion of nursing and health care and thus play an
      integral role in the global health care economy. To meet global health care
      needs, nurses often move within and among countries, creating challenges and
      opportunities for the profession, health care organizations, communities, and
      nations. Researchers, policy makers, and industry and academic leaders must, in
      turn, grapple with the impacts of globalization on the nursing and health care
      workforce. Through this special issue, several key areas for discussion are
      raised. Although far from exhaustive, our intent is to expand and stimulate intra
      and interprofessional conversations raising awareness of the issues, uncover
      unanticipated consequences, and offer solutions for shaping the nursing and
      health care workforce of the future.

PMID- 24462022
TI  - Amphetamine-related disorders in psychiatric emergency service.

PMID- 24462023
TI  - Variation in suicide occurrence by day and during major American holidays.
AB  - BACKGROUND: Due to temporal variations in completed suicides, it has been
      suggested that impulsivity and environmental factors may influence suicide. STUDY
      OBJECTIVE: Our intent was to determine if particular days of the week, seasons,
      or holidays were associated with increased attempted and completed suicides by
      poisoning. METHODS: All calls recorded in the National Poison Database System
      coded as "suspected suicide" from 2006 through 2010 were included. Exposures were
      evaluated by day, season, and holidays, and compared to control dates. RESULTS:
      There were 1,065,067 exposures (63% female) related to suicide attempts, with
      completions in 0.4% of cases. Sundays and Mondays for adults, and Mondays and
      Tuesdays for age < 19 years were the most common. Spring and fall had higher
      numbers of exposures than summer and winter. New Year's Day had a higher number
      of exposures, whereas Independence Day, Thanksgiving, and Christmas had fewer
      exposures. CONCLUSIONS: The beginning of the week, spring and fall, and New
      Year's Day were associated with higher numbers of ingestions with suicidal
      intent. This has implications for clinicians advising potential victims and
      providing emergency care for these patients.

PMID- 24462024
TI  - Case report of electronic cigarettes possibly associated with eosinophilic
      pneumonitis in a previously healthy active-duty sailor.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) are a technology that has been
      touted as a safe and effective alternative to traditional cigarettes. There is,
      however, a paucity of literature showing the adverse outcomes of e-cigarettes and
      a correlation with acute eosinophilic pneumonia (AEP). OBJECTIVE: To present a
      possible association between e-cigarettes and AEP. CASE REPORT: A 20-year-old
      previously healthy man was found to develop AEP after smoking an e-cigarette. He
      was treated with antibiotics and steroids and his symptoms improved. CONCLUSION:
      Though an alternative to traditional cigarettes, e-cigarettes can have
      unpredictable and potentially serious adverse effects. More research needs to be
      conducted to determine their safety. If seeing a patient in the ED with pulmonary
      symptoms after use of e-cigarettes, AEP should be considered in the differential.

PMID- 24462025
TI  - Double simultaneous defibrillators for refractory ventricular fibrillation.
AB  - BACKGROUND: Out-of-hospital cardiac arrest is a leading cause of death in the
      United States. Ventricular fibrillation (VF) is the most common initial rhythm
      after cardiac arrest. OBJECTIVE: To describe a novel approach to the patient with
      intractable VF after cardiac arrest. CASE REPORT: A 51-year old man presented in
      cardiac arrest after a ST-elevation myocardial infarction. He remained in VF
      despite receiving typical therapy including cardiopulmonary resuscitation,
      amiodarone, lidocaine, epinephrine, and five attempts at defibrillation with 200
      J using a biphasic defibrillator. VF was eventually terminated with 400 J by the
      simultaneous use of two biphasic defibrillators. The patient had a full recovery.
      CONCLUSION: We present a case and supportive literature for a novel treatment of
      high-energy defibrillation in a patient with refractory VF.

PMID- 24462026
TI  - Association of emergency department and hospital characteristics with elopements
      and length of stay.
AB  - BACKGROUND: As the Centers for Medicare & Medicaid Services (CMS) core measures
      in 2013 compare Emergency Department (ED) treatment time intervals, it is
      important to identify ED and hospital characteristics associated with these
      metrics to facilitate accurate comparisons. STUDY OBJECTIVES: The objective of
      this study is to assess differences in operational metrics by ED and hospital
      characteristics. ED-level characteristics included annual ED volume, percentage
      of patients admitted, percentage of patients presenting by ambulance, and
      percentage of pediatric patients. Hospital-level characteristics included
      teaching hospital status, trauma center status, hospital ownership (nonprofit or
      for-profit), inpatient bed capacity, critical access status, inpatient bed
      occupancy, and rural vs. urban location area. METHODS: Data from the ED
      Benchmarking Alliance from 2004 to 2009 were merged with the American Hospital
      Association's Annual Survey Database to include hospital characteristics that may
      impact ED throughput. Overall median length of stay (LOS) and left before
      treatment is complete (LBTC) were the primary outcome variables, and a linear
      mixed model was used to assess the association between outcome variables and ED
      and hospital characteristics, while accounting for correlations among multiple
      observations within each hospital. All data were at the hospital level on a
      yearly basis. RESULTS: There were 445 EDs included in the analysis, from 2004 to
      2009, with 850 observations over 6 years. Higher-volume EDs were associated with
      higher rates of LBTC and LOS. For-profit hospitals had lower LBTC and LOS. Higher
      inpatient bed occupancies were associated with a higher LOS. Increasing admission
      percentages were positively associated with overall LOS for EDs, but not with
      rates of LBTC. CONCLUSIONS: Higher-volume EDs are associated with higher LBTC and
      LOS, and for-profit hospitals appear more favorably in these metrics compared
      with their nonprofit counterparts. It is important to appreciate that hospitals
      have different baselines for performance that may be more tied to volume and
      capacity, and less to quality of care.

PMID- 24462027
TI  - Effect of delay in hospital presentation on clinical and imaging findings in
      acute pulmonary thromboembolism.
AB  - BACKGROUND: There is limited information on the extent and clinical importance of
      the delay in hospital presentation of acute pulmonary thromboembolism (PTE).
      OBJECTIVE: The aim of this study was to investigate the delay in hospital
      presentation of PTE and its association with clinical and imaging findings in
      PTE. METHODS: This prospective study was conducted on patients admitted to our
      hospital with a diagnosis of acute PTE between September 2007 and September 2011.
      Relationships between delay in hospital presentation and clinical findings, risk
      factors, imaging findings, and in-hospital mortality were analyzed. RESULTS: Of
      the 195 patients enrolled, 84 (43.1%) patients presented 3 days after the onset
      of symptoms. Patients with chest pain, history of immobility for more than 3
      days, recent surgery, and estrogen use had significantly less delayed
      presentation. Right ventricular dysfunction was significantly more frequent in
      patients with delayed presentation (odds ratio [OR] = 2.38; 95% confidence
      interval [CI] 1.27-4.44; p = 0.006); however, no relationship was found between
      delay in presentation and pulmonary computed tomographic angiography or color
      Doppler sonography findings. Patients with delayed presentation were at higher
      risk of in-hospital mortality (OR = 4.32; 95% CI 1.12-16.49; p = 0.021).
      CONCLUSIONS: Our study showed that a significant portion of patients with acute
      PTE had delayed presentation. Also, patients with delayed presentation had worse
      echocardiographic findings and higher in-hospital mortality.

PMID- 24462028
TI  - Worrisome facial swelling.

PMID- 24462029
TI  - Crazy paving on computed tomography after marijuana use.

PMID- 24462030
TI  - Physician identification and patient satisfaction in the emergency department:
      are they related?
AB  - BACKGROUND: Patient satisfaction has become a quality indicator tracked closely
      by hospitals and emergency departments (EDs). Unfortunately, the primary factors
      driving patient satisfaction remain poorly studied. It has been suggested that
      correct physician identification impacts patient satisfaction in hospitalized
      patients, however, the limited studies that exist have demonstrated mixed
      results. OBJECTIVES: In this study, we sought to identify factors associated with
      improved satisfaction among ED patients, and specifically, to test whether
      improving physician identification by patients would lead to increased
      satisfaction. METHODS: We performed a pre- and postintervention, survey-based
      study of patients at the end of their ED visits. We compared patient satisfaction
      scores as well as patients' abilities to correctly identify their physicians over
      two separate 1-week periods: prior to and after introducing a multimedia
      presentation of the attending physicians into the waiting room. RESULTS: A total
      of 486 patients (25% of all ED visits) were enrolled in the study. In the
      combined study population, overall patient satisfaction was higher among patients
      who correctly identified their physicians than among those who could not identify
      their physicians (combined mean satisfaction score of 8.1 vs. 7.2; odds ratio
      [OR] 1.07). Overall satisfaction was also higher among parents or guardians of
      pediatric patients than among adult patients (satisfaction score of 8.4 vs. 7.4;
      OR 1.07), and among patients who experienced a shorter door-to-doctor time
      (satisfaction score of 8.2 for shorter waiting time vs. 5.6 for longer waiting
      time; OR 1.15). Ambulance patients showed decreased satisfaction over some
      satisfaction parameters, including physician courtesy and knowledge. No direct
      relationship was demonstrated between the study intervention (multimedia
      presentation) and improved patient satisfaction or physician identification.
      CONCLUSIONS: Improved patient satisfaction was found to be positively correlated
      with correct physician identification, shorter waiting times, and among the
      pediatric patient population. Further studies are needed to determine
      interventions that improve patients' abilities to identify their physicians and
      lower waiting times.

PMID- 24462031
TI  - The multiple mini-interview for emergency medicine resident selection.
AB  - BACKGROUND: The Multiple Mini-Interview (MMI) uses multiple, short-structured
      contacts to evaluate communication and professionalism. It predicts medical
      school success better than the traditional interview and application. Its
      acceptability and utility in emergency medicine (EM) residency selection are
      unknown. OBJECTIVE: We theorized that participants would judge the MMI equal to a
      traditional unstructured interview and it would provide new information for
      candidate assessment. METHODS: Seventy-one interns from 3 programs in the first
      month of training completed an eight-station MMI focused on EM topics. Pre- and
      post-surveys assessed reactions. MMI scores were compared with application data.
      RESULTS: EM grades correlated with MMI performance (F[1, 66] = 4.18; p < 0.05)
      with honors students having higher scores. Higher third-year clerkship grades
      were associated with higher MMI performance, although this was not statistically
      significant. MMI performance did not correlate with match desirability and did
      not predict most other components of an application. There was a correlation
      between lower MMI scores and lower global ranking on the Standardized Letter of
      Recommendation. Participants preferred a traditional interview (mean difference =
      1.36; p < 0.01). A mixed format (traditional interview and MMI) was preferred
      over a MMI alone (mean difference = 1.1; p < 0.01). MMI performance did not
      significantly correlate with preference for the MMI. CONCLUSIONS: Although the
      MMI alone was viewed less favorably than a traditional interview, participants
      were receptive to a mixed-methods interview. The MMI does correlate with
      performance on the EM clerkship and therefore can measure important abilities for
      EM success. Future work will determine whether MMI performance predicts residency
      performance.

PMID- 24462032
TI  - Ultrasound-guidance can reduce adverse events during femoral central venous
      cannulation.
AB  - BACKGROUND: Ultrasound-guidance for internal jugular central venous cannulation
      (CVC) has become the recommended best practice and has been shown to improve
      placement success and reduce complications. There is a dearth of studies that
      evaluate emergency point-of-care ultrasound guidance of femoral CVC. OBJECTIVE:
      Our aim was to determine if point-of-care ultrasound guidance for femoral CVC
      decreases adverse events and increases the likelihood of successful placement
      when compared with the landmark technique. METHODS: We conducted an Institutional
      Review Board-approved, prospective, observational study of consecutive patients
      who required CVC. Physicians who performed CVC completed a standardized, web
      based data sheet for a national CVC registry. We evaluated single-institution
      data regarding CVC site, ultrasound usage, CVC indication, and mechanical
      complications (e.g., pneumothorax, arterial puncture, failed access, catheter
      misdirection, and hematoma). The study period was between January 2006 and June
      2010. Analysis using Pearson's chi(2) and Agresti-Coull binomial confidence
      intervals was performed; significance was defined as p < 0.05. RESULTS: We
      evaluated data for 143 patients who had femoral CVC in our institution. Sixty
      CVCs (42%) were performed under ultrasound guidance, 83 (58%) via landmark
      technique (p = 0.0159); 3.3% of femoral central venous lines placed by ultrasound
      guidance had recorded adverse events compared with 9.6% for the landmark
      technique (p = 0.145). There was no statistically significant difference in
      complications between ultrasound-guidance and landmark techniques. Our data
      showed a trend toward decreased rates of arterial puncture and reduced
      cannulation attempts resulting in improved placement success. CONCLUSIONS: Our
      experience shows that ultrasound guidance for femoral CVC might decrease
      complications and improve placement success, although we cannot recommend this
      approach without additional data. We recommend a larger study to further evaluate
      this technique.

PMID- 24462033
TI  - Shared liability? Consultants, pharmacists, and the emergency physician: legal
      cases and caveats.
AB  - In caring for patients in the Emergency Department (ED), the emergency physician
      (EP) will often utilize consulting specialists and pharmacists. In the event of
      an untoward patient outcome, disagreement may arise regarding the liability of
      each provider. Here, we review a series of malpractice cases involving consulting
      physicians and pharmacists to illustrate the legal principles of physician
      patient relationships and physician duty. Determination of liability in the
      courts will rest, in part, on whether a physician-patient relationship was formed
      via an "affirmative act". Consulting physicians may establish a relationship
      through an overt or implied agreement to participate in a patient's care, or by
      reviewing specific tests and studies for the purpose of diagnosis and treatment.
      The courts have defined the duty of the pharmacist to safely dispense medication,
      and have ascribed the duty to warn of medication side effects to the prescribing
      physician. 

PMID- 24462034
TI  - Management of benign paroxysmal positional vertigo: a randomized controlled
      trial.
AB  - BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a common presenting
      problem. OBJECTIVE: Our aim was to compare the efficacy of vestibular
      rehabilitation (maneuver) vs. conventional therapy (medications) in patients
      presenting to the emergency department (ED) with BPPV. METHODS: This was a
      prospective, single-blinded physician, randomized pilot study comparing two
      groups of patients who presented to the ED with a diagnosis of BPPV at a Level 1
      trauma center with an annual census of approximately 75,000. The first group
      received standard medications and the second group received a canalith
      repositioning maneuver. The Dizziness Handicap Inventory was used to measure
      symptom resolution. RESULTS: Twenty-six patients were randomized; 11 to the
      standard treatment arm and 15 to the interventional arm. Mean age +/- standard
      deviation of subjects randomized to receive maneuver and medication were 59 +/-
      12.6 years and 64 +/- 11.2 years, respectively. There was no significant
      difference in mean ages between the two treatment arms (p = 0.310). Two hours
      after treatment, the symptoms between the groups showed no difference in measures
      of nausea (p = 0.548) or dizziness (p = 0.659). Both groups reported a high level
      of satisfaction, measured on a 0-10 scale. Satisfaction in subjects randomized to
      receive maneuver and medication was 9 +/- 1.5 and 9 +/- 1.0, respectively; there
      was no significant difference in satisfaction between the two arms (p = 0.889).
      Length of stay during the ED visit did not differ between the treatment groups (p
      = 0.873). None of the patients returned to an ED for similar symptoms.
      CONCLUSIONS: This pilot study shows promise, and would suggest that there is no
      difference in symptomatic resolution, ED length of stay, or patient satisfaction
      between standard medical care and canalith repositioning maneuver. Physicians
      should consider the canalith repositioning maneuver as a treatment option.

PMID- 24462035
TI  - A deadly digital dressing: a case of surgical decompression for finger ischemia
      due to circumferential finger dressing.
AB  - BACKGROUND: Tubular gauze dressings are commonly used, but have potential to
      cause iatrogenic finger ischemia. OBJECTIVES: To inform health care providers of
      an avoidable complication and to discuss appropriate methods of prevention and
      treatment. CASE REPORT: We discuss a teenage female's finger that narrowly
      avoided amputation after a tubular gauze dressing caused iatrogenic ischemia.
      Surgical decompression using a novel technique successfully salvaged the finger.
      Operative intervention for this complication has previously been unreported.
      CONCLUSION: It is important that circumferential digital dressings are applied
      correctly. Vascular insufficiency from an occlusive dressing is an iatrogenic and
      avoidable complication. Successful operative decompression may be indicated to
      minimize tissue loss and improve circulation.

PMID- 24462036
TI  - Developing a curriculum for emergency medicine residency orientation programs.
AB  - BACKGROUND: New residents enter emergency medicine (EM) residency programs with
      varying EM experiences, which makes residency orientation programs challenging to
      design. There is a paucity of literature to support best practices. OBJECTIVE: We
      report on a curriculum development project for EM residency orientation using the
      Kern Model. CURRICULUM: Components of the revised curriculum include
      administrative inculcation into the program; delivering skills and knowledge
      training to ensure an entering level of competence; setting expectations for
      learning in the overall residency curriculum; performing an introductory
      performance evaluation; and socialization into the program. RESULTS: Post
      implementation resident surveys found the new curriculum to be helpful in
      preparing them for the first year of training. CONCLUSIONS: The Kern Model was a
      relevant and useful method for redesigning a new-resident orientation curriculum.

PMID- 24462037
TI  - Paravannella minima n. g. n. sp. (Discosea, Vannellidae) and distinction of the
      genera in the vannellid amoebae.
AB  - Paravannella minima n. g. n. sp. (Amoebozoa, Vannellidae) isolated from a
      freshwater aquarium, possesses all light-microscopic and ultrastructural
      characteristics of the genus Vannella, being one of the smallest species among
      the vannellid amoebae (cell size during locomotion usually between 4.5 and
      10MUm). At the same time, sequence analysis of the genes encoding for nuclear SSU
      rRNA, actin and mitochondrial Cox1 shows this species as the earliest-branching
      vannellid that appears to be sister to the rest of this clade. This is correlated
      with the presence of some plesiomorphic characters; in particular, the secondary
      structure of the hypervariable helices E23-1-E23-7 in the studied species is
      shared with Vannella and most of the genera of Dactylopodida. The cell coat
      structure of the studied species corresponds to the hypothesis that vannellid
      amoebae were ancestrally enclosed in a cell coat consisting of pentagonal
      glycostyles that have undergone multiple independent losses in various clades of
      Vannellidae. 

PMID- 24462038
TI  - Flow cytometric differentiation of abnormal and normal plasma cells in the bone
      marrow in patients with multiple myeloma and its precursor diseases.
AB  - Flow cytometric (FC) enumeration of abnormal plasma cells (APCs) for diagnosis
      and prognostication of plasma cell dyscrasias (PCD) is challenging. We studied
      antigen expression in normal plasma cells (NPC) (N = 34) and APC in a series of
      unselected PCD (N = 59). NPC subpopulations often demonstrated CD19(-), CD20(+),
      CD45(-) or dim and CD56(+), an immunophenotype observed in PCD. However abnormal
      CD81 was only observed in APCs (APC detection sensitivity 95%; specificity 100%).
      We evaluated differences in antigen expression patterns among MGUS (N = 14), SMM
      (N = 35) and MM (N = 10), finding the combination of CD45 and CD56 helpful in
      differentiating MGUS from SMM and MM (p = 0.0002).

PMID- 24462039
TI  - Photoreceptor-derived activin promotes dendritic termination and restricts the
      receptive fields of first-order interneurons in Drosophila.
AB  - How neurons form appropriately sized dendritic fields to encounter their
      presynaptic partners is poorly understood. The Drosophila medulla is organized in
      layers and columns and innervated by medulla neuron dendrites and photoreceptor
      axons. Here, we show that three types of medulla projection (Tm) neurons extend
      their dendrites in stereotyped directions and to distinct layers within a single
      column for processing retinotopic information. In contrast, the Dm8 amacrine
      neurons form a wide dendritic field to receive ~16 R7 photoreceptor inputs. R7-
      and R8-derived Activin selectively restricts the dendritic fields of their
      respective postsynaptic partners, Dm8 and Tm20, to the size appropriate for their
      functions. Canonical Activin signaling promotes dendritic termination without
      affecting dendritic routing direction or layer. Tm20 neurons lacking Activin
      signaling expanded their dendritic fields and aberrantly synapsed with
      neighboring photoreceptors. We suggest that afferent-derived Activin regulates
      the dendritic field size of their postsynaptic partners to ensure appropriate
      synaptic partnership.

PMID- 24462040
TI  - Central terminal sensitization of TRPV1 by descending serotonergic facilitation
      modulates chronic pain.
AB  - The peripheral terminals of primary nociceptive neurons play an essential role in
      pain detection mediated by membrane receptors like TRPV1, a molecular sensor of
      heat and capsaicin. However, the contribution of central terminal TRPV1 in the
      dorsal horn to chronic pain has not been investigated directly. Combining primary
      sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model,
      we detected robust neuronal hyperactivity in injured and uninjured nerves in the
      skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal
      nucleus. Extensive TRPV1 hyperactivity was observed in central terminals
      innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was
      maintained by descending serotonergic (5-HT) input from the brainstem. Central
      blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal
      sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in
      the territories of injured and uninjured nerves. Our results reveal central
      mechanisms facilitating central terminal sensitization underlying chronic pain.

PMID- 24462042
TI  - Impact of patient selection and study characteristics on signal detection in
      placebo-controlled trials with antidepressants.
AB  - An increasing rate of antidepressant trials fail due to large placebo responses.
      This analysis aimed to identify variables influencing signal detection in
      clinical trials of major depressive disorder. Patient-level data of randomized
      patients with a duloxetine dose >= 60 mg/day were obtained from Lilly. Total
      scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy
      endpoints. In total, 4661 patients from 14 studies were included in the analysis.
      The overall effect size (ES), based on the HAM-D total score at endpoint, between
      duloxetine and placebo was -0.272. Although no statistically significant
      interactions were found, the following results for factors influencing ES were
      seen: a very low ES (-0.157) in patients in the lowest baseline HAM-D category
      and in patients recruited in the last category of the recruitment period (
      0.122). A higher ES in patients recruited in centers with a site-size at but not
      more than 2.5 times the average site-size for the study (-0.345). Study
      characteristics that resulted in low signal detection in our database were: <80%
      study completers, a HAM-D placebo response >5 points, a high variability of
      placebo response (SD > 7 points HAM-D), >6 post baseline visits per study, and
      use of an active control drug. Simpler trial designs, more homogeneous and mid
      sized study sites, a primary analysis based on a higher cutoff blinded to
      investigators to avoid the influence of score inflation in mild patients and, if
      possible, studies without an active control group could lead to a better signal
      detection of antidepressive efficacy.

PMID- 24462041
TI  - A diffusion tensor imaging study of suicide attempters.
AB  - BACKGROUND: Few studies have examined white matter abnormalities in suicide
      attempters using diffusion tensor imaging (DTI). This study sought to identify
      white matter regions altered in individuals with a prior suicide attempt.
      METHODS: DTI scans were acquired in 13 suicide attempters with major depressive
      disorder (MDD), 39 non-attempters with MDD, and 46 healthy participants (HP).
      Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were
      determined in the brain using two methods: region of interest (ROI) and tract
      based spatial statistics (TBSS). ROIs were limited a priori to white matter
      adjacent to the caudal anterior cingulate cortex, rostral anterior cingulate
      cortex, dorsomedial prefrontal cortex, and medial orbitofrontal cortex. RESULTS:
      Using the ROI approach, suicide attempters had lower FA than MDD non-attempters
      and HP in the dorsomedial prefrontal cortex. Uncorrected TBSS results confirmed a
      significant cluster within the right dorsomedial prefrontal cortex indicating
      lower FA in suicide attempters compared to non-attempters. There were no
      differences in ADC when comparing suicide attempters, non-attempters and HP
      groups using ROI or TBSS methods. CONCLUSIONS: Low FA in the dorsomedial
      prefrontal cortex was associated with a suicide attempt history. Converging
      findings from other imaging modalities support this finding, making this region
      of potential interest in determining the diathesis for suicidal behavior.

PMID- 24462043
TI  - White fish reduces cardiovascular risk factors in patients with metabolic
      syndrome: the WISH-CARE study, a multicenter randomized clinical trial.
AB  - BACKGROUND AND AIMS: Reduction of cardiovascular risk with high consumption of
      fish in diet is still a matter of debate, and concerns about heavy metal
      contamination have limited consumption of oily fish. We aimed to evaluate the
      effect of regular ingestion of white fish on cardiovascular risk factors in
      patients with metabolic syndrome. METHODS AND RESULTS: Multicenter randomized
      crossover clinical trial including 273 individuals with metabolic syndrome. An 8
      week only-one dietary intervention: 100 g/d of white fish (Namibia hake) with
      advice on a healthy diet, compared with no fish or seafood with advice on a
      healthy diet. Outcomes were lipid profile, individual components of the metabolic
      syndrome, serum insulin concentrations, homeostasis model of insulin resistance,
      serum C-reactive protein and serum fatty acid levels. We found a significant
      lowering effect of the intervention with white fish on waist circumference (P <
      0.001) and diastolic blood pressure (P = 0.014). A significant lowering effect
      was also shown after the dietary intervention with fish on serum LDL
      concentrations (P = 0.048), whereas no significant effects were found on serum
      HDL or triglyceride concentrations. A significant rise (P < 0.001) in serum EPA
      and DHA fatty acids was observed following white fish consumption. Overall
      adherence to the intervention was good and no adverse events were found.
      CONCLUSION: In individuals with metabolic syndrome, regular consumption of hake
      reduces LDL cholesterol concentrations, waist circumference and blood pressure
      components of the metabolic syndrome. CLINICAL TRIAL REGISTRY: White Fish for
      Cardiovascular Risk Factors in Patients with Metabolic Syndrome Study, Registered
      under ClinicalTrials.gov Identifier: NCT01758601.

PMID- 24462045
TI  - Response to the letter by Testino et al. on moderate alcohol use and health.

PMID- 24462044
TI  - The association between APOA5 haplotypes and plasma lipids is not modified by
      energy or fat intake: the Czech HAPIEE study.
AB  - BACKGROUND AND AIMS: Several smaller studies reported interactions between
      dietary factors and apolipoprotein A5 (APOA5) gene polymorphisms in determination
      of plasma lipids. We tested interactions between APOA5 haplotypes and dietary
      intake in determination of plasma triglycerides (TG) and other lipids. METHODS
      AND RESULTS: Participants (5487 males and females aged 45-69) were classified
      according to the number (0, 1, 2+) of minor APOA5 alleles (using T-1131 > C;
      rs662799 and Ser19 > Trp; rs3135506 polymorphisms) and into three groups of low
      (bottom 25%), medium (26th-75th percentile) and high (top 25%) of intake of total
      energy and total, saturated and polyunsaturated fats, assessed by food frequency
      questionnaire. The age-sex adjusted geometric means of plasma TG increased with
      the number of minor alleles, from 1.57 (standard error 0.01), to 1.79 (0.02) to
      2.29 (0.10) mmol/L (p < 0.00001) but TG did not differ between groups with low,
      medium and high total energy intake (p = 0.251). TG concentrations were highest
      in subjects with the combination of 2+ minor alleles and the highest energy
      intake (mean 2.59 [0.19], compared with 1.62 [0.03] in subjects with lowest
      energy intake and no minor allele) but the interaction between energy intake and
      APOA5 haplotypes was not statistically significant (p = 0.186). Analogous
      analyses with total, saturated and polyunsaturated fat intake yielded similar
      nonsignificant results. Effects of APOA5 and dietary intakes on total and HDL
      cholesterol were weaker and no interactions were significant. CONCLUSION: In this
      Slavic Caucasian population sample, we did not detect the hypothesized
      interaction between common SNPs within the APOA5 gene and diet in determination
      of blood lipids.

PMID- 24462046
TI  - Under-treatment of migrants with diabetes in a universalistic health care system:
      the ARNO Observatory.
AB  - AIMS: To assess whereas prevalence, treatment and direct costs of drug-treated
      diabetes were similar in migrants and in people of Italian citizenship under the
      universalistic Italian health care system. METHODS AND RESULTS: Drug-treated
      diabetic individuals were identified in the population-based multiregional ARNO
      Observatory on the basis of 2010 prescriptions. Migrants were identified by the
      country-of-birth code on the fiscal identification code. Diabetes prevalence was
      calculated for Italians (n = 7,328,383) and migrants (n = 527,965). To assess the
      odds of migrants of having diabetes compared to Italians, we individually matched
      all migrants to Italians for major confounders (age, sex and place of residence).
      Finally, all migrants with diabetes were individually matched for confounders to
      Italians with diabetes to compare prescriptions, hospitalization rates, services
      use and direct costs for the National Health System. We identified 368,797
      subjects with diabetes among Italians and 10,336 among migrants, giving
      prevalence of 5.03% and 1.96%, respectively. Migrants with diabetes were younger
      than Italians (52 +/- 13 years vs. 68 +/- 14 years, P < 0.001); after matching,
      their risk of disease was higher (odds ratio, 1.55, 95% confidence interval, 1.50
      1.60). The total cost was 27% lower in migrants, due to lower cost of drugs (
      29%), hospital admission (-27%) and health services (-22%). The number of
      packages/treated person-year of all glucose-lowering drugs was also lower in
      migrants (-15%) (P < 0.001). CONCLUSIONS: Compared to subjects of Italian
      ancestry, migrants to Italy show a higher risk of diabetes but less intense
      treatment. Inequalities in health care use are likely and are maintained also in
      a universalistic system.

PMID- 24462047
TI  - Increased density of inhibitory noradrenergic parenchymal nerve fibers in
      hypertrophic islets of Langerhans of obese mice.
AB  - BACKGROUND AND AIM: We sought to identify mechanisms of beta cell failure in
      genetically obese mice. Little is known about the role of pancreatic innervation
      in the progression of beta cell failure. In this work we studied adrenergic
      innervation, in view of its potent inhibitory effect on insulin secretion. We
      analyzed genetically obese ob/ob and db/db mice at different ages (6- and 15-week
      old), corresponding to different compensatory stages in the course of beta cell
      dysfunction. 15 week-old HFD mice were also studied. METHODS AND RESULTS: All
      mice were characterized by measures of plasma glucose, insulin, and HOMA. After
      perfusion, pancreata were dissected and studied by light microscopy, electron
      microscopy, and morphometry. Insulin, Tyrosine Hydroxylase-positive fibers and
      cells and Neuropeptide Y-positive cells were scored by immunohistochemistry.
      Islets of obese mice showed increased noradrenergic fiber innervation, with
      significant increases of synaptoid structures contacting beta cells compared to
      controls. Noradrenergic innervation of the endocrine area in obese db/db mice
      tended to increase with age, as diabetes progressed. In ob/ob mice, we also
      detected an age-dependent trend toward increased noradrenergic innervation that,
      unlike in db/db mice, was unrelated to glucose levels. We also observed a
      progressive increase in Neuropeptide Y-immunoreactive elements localized to the
      islet core. CONCLUSIONS: Our data show increased numbers of sympathetic nerve
      fibers with a potential to convey inhibitory signals on insulin secretion in
      pancreatic islets of genetically obese animals, regardless of their diabetic
      state. The findings suggest an alternative interpretation of the pathogenesis of
      beta cell failure, as well as novel strategies to reverse abnormalities in
      insulin secretion.

PMID- 24462048
TI  - Daily macro and micronutrient supply for patients on total enteral nutrition: are
      they in keeping with new dietary reference intakes for the Italian population?

PMID- 24462049
TI  - Electrocardiographic changes associated with insulin resistance.
AB  - BACKGROUND AND AIM: Cardiac steatosis has been related to increased risk of heart
      disease. We investigated the association between cardiac steatosis,
      electrocardiographic (ECG) abnormalities, and individual components of the
      metabolic syndrome (MetS). METHODS AND RESULTS: A 12-lead ECG and laboratory data
      were examined in 31 men with the MetS and in 38 men without the MetS. Myocardial
      triglyceride (MTG) content was measured with 1.5 T magnetic resonance (MR)
      spectroscopy and epicardial and pericardial fat by MR imaging. MTG content,
      epicardial and pericardial fat depots were higher in men with the MetS compared
      with subjects without the MetS (p < 0.001). The heart rate was increased (p <
      0.001), the PR interval was longer (p < 0.044), the frontal plane QRS axis
      shifted to the left (p < 0.001), and the QRS voltage (p < 0.001) was lower in
      subjects with the MetS. The frontal plane QRS axis and the QRS voltage were
      inversely correlated with MTG content, waist circumference (WC), body mass index
      (BMI), TGs, and fasting blood glucose. High-density lipoprotein cholesterol
      correlated positively and measures of insulin resistance negatively with the QRS
      voltage. MTG content and hypertriglyceridemia were determinants of the frontal
      plane QRS and WC and hyperglycemia were predictors of the QRS voltage.
      CONCLUSION: The MetS and cardiac steatosis appear to associate with multiple
      changes on 12-lead ECG. The frontal plane QRS axis is shifted to the left and the
      QRS voltage is lower in subjects with the MetS. Standard ECG criteria may
      underestimate the presence of left ventricular hypertrophy in obese subjects with
      cardiometabolic risk factors.

PMID- 24462050
TI  - Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time
      dependent and related to cardiac hemodynamics in diabetic rats.
AB  - BACKGROUND AND AIMS: Trans-resveratrol (RSV) is a natural compound occurring in
      different foods and plants, which in vivo is rapidly conjugated with glucuronic
      acid and sulfate. Despite its demonstrated cardioprotective activity, the
      bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown.
      METHODS AND RESULTS: Diabetic rats were randomized to 1, 3 or 6 weeks of RSV
      treatment at two different doses (1 or 5 mg/kg/day). A dose and time-dependent
      accumulation was observed, with no detectable levels of RSV metabolites found in
      heart tissues after 1 week and significant concentrations of RSV-3-sulfate and
      RSV-3-glucuronide after 6 weeks of treatment (0.05 nmol/g of tissue and 0.01
      nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was
      accompanied by an improvement of cardiac function in long-term diabetes, when
      myocardial morpho-functional damage is more evident, with an almost complete
      recovery of all hemodynamic parameters, at the highest RSV dose. CONCLUSION: Even
      if a higher concentration of RSV in tissues cannot be ruled out after constant
      oral administration, an accumulation coherent with what is usually evaluated in
      cell based mechanistic studies is largely unattainable and the RSV unconjugated
      form would not be present in this paradigm. The current investigation provides
      data on myocardial tissue concentrations of RSV metabolites, after short/medium
      term RSV treatment. This knowledge constitutes a basic requirement for future
      studies aimed at reliably defining the molecular pathways underlying RSV-mediated
      cardioprotective effects and opens up new perspectives for research focused on
      testing phenolic compounds as adjuvants in degenerative heart diseases.

PMID- 24462051
TI  - Back to the future: the Mediterranean diet paradigm.
AB  - The Mediterranean diet was introduced to the scientific community by the classic
      Seven Countries study. Since then data on the association between this diet and
      cardiovascular disease, cancer and other chronic diseases have been accumulating.
      The Mediterranean diet is characterized by a high intake of olive oil, plant
      products, fish and seafood; a low intake of dairies, meat and meat products; and
      a moderate ethanol intake. The Mediterranean diet has been operationalized
      through various computational scores (e.g. the Mediterranean diet score for
      adults and the KIDMED index for children) which are all based on the dietary
      components that capture its essence. Next to evidence generated through both
      observational studies and intervention trials on the inverse association between
      Mediterranean diet and several risk factors, inflammatory markers and mortality
      or incidence of disease, there is increasing evidence that Mediterranean
      populations are abandoning their traditional eating habits. Publications
      presenting changes over time in the diet of populations participating in the
      Seven Countries Study point towards an increase in the intake of processed foods
      and saturated fat and a decrease in the intake of plant foods and monounsaturated
      fatty acids. Findings are alarming, particularly in relation to younger
      generations. Studies among children and adolescents in the Mediterranean region
      clearly indicate that the largest proportions of these populations poorly adhere
      to their traditional diet. Mediterraneans have clearly not been the major
      benefactors in the research on the effects of the Mediterranean lifestyle and
      younger populations in the regions are already following the wrong path. 

PMID- 24462052
TI  - Intrahepatic cholestasis of pregnancy is associated with an increased risk of
      gestational diabetes.
AB  - OBJECTIVE: To evaluate the association between intrahepatic cholestasis of
      pregnancy (ICP) and gestational diabetes mellitus (GDM). STUDY DESIGN: A
      retrospective case-control study of pregnancy outcomes in 57,724 women managed at
      a university teaching hospital in Rhode Island, USA, in whom universal screening
      for GDM had been performed and who were assessed for the incidence of ICP.
      Pregnancies complicated by ICP or GDM between February 2005 and June 2011 were
      identified from the electronic patient records using appropriate ICD codes. A
      total of 125 cases were required to detect a difference in the incidence of GDM
      in ICP at 5% significance with 80% power. Demographic and clinical outcome data
      (including maternal age, ethnic group, BMI, and infant weight and gender) were
      also collected. RESULTS: Of the 57,724 pregnancies, 143 were complicated by ICP
      (0.25%) and 4880 by GDM (8.5%). Nineteen ICP cases had GDM. The incidence of GDM
      in ICP was 13.6% (19/140, OR 1.68 CI 1.04-2.72). Where gestational ages were
      available (n=105), of those screened for GDM prior to developing ICP, 13.4%
      (11/82, OR 1.64 CI 0.88-3.06) had a confirmed diagnosis, rising to 30% (7/23, OR
      4.69 CI 1.98-11.1) in cases that were screened following the onset of
      cholestasis. Simple linear regression analysis of adjusted birth weight centiles
      in ICP revealed a significant linear trend of increasing centiles with
      gestational age (p=0.005). CONCLUSIONS: These data support the hypothesis that
      the incidence of GDM is higher in women predisposed to developing ICP. It is
      likely that this susceptibility increases further following the onset of
      cholestasis.

PMID- 24462053
TI  - Positive health outcomes following health-promoting and disease-preventive
      interventions for independent very old persons: long-term results of the three
      armed RCT Elderly Persons in the Risk Zone.
AB  - The aim of this study was to analyze the long-term effect of the two health
      promoting and disease-preventive interventions, preventive home visits and senior
      meetings, with respect to morbidity, symptoms, self-rated health and satisfaction
      with health. The study was a three-armed randomized, single-blind, and controlled
      trial, with follow-ups at one and two years after interventions. A total of 459
      persons aged 80 years or older and still living at home were included in the
      study. Participants were independent in ADL and without overt cognitive
      impairment. An intention-to-treat analysis was performed. The result shows that
      both interventions delayed a progression in morbidity, i.e. an increase in CIRS-G
      score (OR=0.44 for the PHV and OR=0.61 for senior meetings at one year and
      OR=0.60 for the PHV and OR=0.52 for the senior meetings at two years) and
      maintained satisfaction with health (OR=0.49 for PHV and OR=0.57 for senior
      meetings at one year and OR=0.43 for the PHV and OR=0.28 for senior meetings
      after two years) for up to two years. The intervention senior meetings prevented
      a decline in self-rated health for up to one year (OR=0.55). However, no
      significant differences were seen in postponing progression of symptoms in any of
      the interventions. This study shows that it is possible to postpone a decline in
      health outcomes measured as morbidity, self-rated health and satisfaction with
      health in very old persons at risk of frailty. Success factors might be the multi
      dimensional and the multi-professional approach in both interventions. TRIAL
      REGISTRATION: NCT0087705.

PMID- 24462054
TI  - [Radiation therapy of sinonasal natural killer/T-cell lymphoma].
AB  - Natural killer (NK)/T-cell lymphoma are part of lymphoproliferative diseases,
      they are rare in Europe and the United States but relatively common in Asia and
      South America. Natural killer (NK)/T-cell lymphoma present clinically as
      destructive lesions of the upper aerodigestive tract with perforation of deep
      structures of the face, destruction of the palate or an invasion of orbits.
      Treatment modalities of these lymphomas are still discussed because of the lack
      of available studies and the rarity of this disease. Radiotherapy provides a
      rapid control of the disease and is positioned as a major treatment of localized
      stages of NK/T-cell lymphoma of the nasal cavity. We therefore studied the
      different forms of radiation therapy in the early stages of nasal NK/T-cell
      lymphoma. 

PMID- 24462055
TI  - Chronic endometritis in women with recurrent early pregnancy loss and/or fetal
      demise.
AB  - OBJECTIVE: To assess the prevalence of chronic endometritis in women with a
      history of recurrent early pregnancy loss (REPL) and/or fetal demise (FD).
      DESIGN: Observational cohort study using prospectively collected data. SETTING:
      Recurrent pregnancy loss program in an academic medical center. PATIENT(S): Three
      hundred ninety-five women with a history of two or more pregnancy losses of less
      than 10 weeks' size or a fetal demise of 10 or more weeks' size. INTERVENTION(S):
      All women had an endometrial biopsy. Chronic endometritis was treated with
      antibiotics, and a second endometrial biopsy was recommended as a "test of cure."
      MAIN OUTCOME MEASURE(S): Subsequent live-birth rate (LBR). RESULT(S): The overall
      prevalence of chronic endometritis was 9% (35/395) in this cohort; 7% (21/285) in
      the REPL group, 14% (8/57) in the FD group, and 11% (6/53) in the combined
      REPL/FD group. The cure rate was 100% after a course(s) of antibiotics. The
      subsequent cumulative LBR was 88% (21/24) for the treated chronic endometritis
      group versus 74% (180/244) for the group without chronic endometritis. The per
      pregnancy LBR for the treated chronic endometritis group was 7% (7/98) before
      treatment versus 56% (28/50) after treatment. CONCLUSION(S): There was a high
      prevalence of chronic endometritis in this cohort. The test of cure was 100% with
      antibiotics. Subsequent LBRs after treatment were encouraging.

PMID- 24462056
TI  - First-trimester Down syndrome screening after assisted conception.

PMID- 24462057
TI  - Oocyte number as a predictor for ovarian hyperstimulation syndrome and live
      birth: an analysis of 256,381 in vitro fertilization cycles.
AB  - OBJECTIVE: To investigate the association between oocyte number and the rates of
      ovarian hyperstimulation syndrome (OHSS) and live birth (LB) in fresh autologous
      in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study. SETTING:
      An academic reproductive medicine practice. PATIENT(S): We analyzed data from
      256,381 IVF cycles using the 2008-2010 Society for Assisted Reproductive
      Technology national registry. Patients were divided into five groups based on
      retrieved oocyte number. MAIN OUTCOME MEASURE(S): Rates of OHSS and LB were
      calculated for each group. A generalized estimating equation (GEE) was used to
      assess differences in OHSS and LB between groups. Receiver operating
      characteristic (ROC) curves were used to evaluate oocyte number as a predictor of
      OHSS and LB. INTERVENTION(S): None. RESULT(S): The LB rate increased up to 15
      oocytes, then plateaued (0-5: 17%, 6-10: 31.7%; 11-15: 39.3%; 16-20: 42.7%; 21
      25: 43.8%; and >25 oocytes: 41.8%). However, the rate of OHSS became much more
      clinically significant after 15 oocytes (0-5: 0.09%; 6-10: 0.37%; 11-15: 0.93%;
      16-20: 1.67%; 21-25: 3.03%; and >25 oocytes: 6.34%). These trends remained after
      adjustment with the use of GEE. ROC curves revealed that although oocyte number
      is not useful in the prediction of LB, 15 retrieved oocytes is the number that
      best predicts OHSS risk. CONCLUSION(S): Retrieval of >15 oocytes significantly
      increases OHSS risk without improving LB rate in fresh autologous IVF cycles. In
      general, less aggressive stimulation protocols should be considered, especially
      in high-responders, to optimize outcomes.

PMID- 24462058
TI  - Reply of the authors.

PMID- 24462059
TI  - A new step toward the artificial ovary: survival and proliferation of isolated
      murine follicles after autologous transplantation in a fibrin scaffold.
AB  - OBJECTIVE: To create an artificial ovary to provide an alternative way of
      restoring fertility in patients who cannot benefit from transplantation of
      cryopreserved ovarian tissue due to the threat of reintroducing malignant cells.
      DESIGN: In vivo experimental study. SETTING: Gynecology research unit in a
      university hospital. ANIMAL(S): Six-week-old female NMRI mice. INTERVENTION(S):
      Autografting of isolated preantral follicles and ovarian cells (OCs) encapsulated
      in two fibrin matrices containing low concentrations of fibrinogen (F; mg/mL) and
      thrombin (T; IU/mL): F12.5/T1 and F25/T4. MAIN OUTCOME MEASURE(S): Follicular
      density and development, OC survival and proliferation, inflammatory response,
      and vascularization. RESULT(S): After 1 week, the follicle recovery rate ranged
      from 30.8% (F25/T4) to 31.8% (F12.5/T1). With both fibrin formulations, all
      follicles were found to be alive or minimally damaged, as demonstrated by
      terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, and
      at the growing stage (primary, secondary, and antral follicles), confirmed by
      Ki67 immunostaining. Isolated OCs also survived and proliferated after grafting,
      as evidenced by <1% apoptotic cells and a high proportion of Ki67-positive cells.
      Vessels were found in both fibrin formulations, and the global vascular surface
      area varied from 1.35% (F25/T4) to 1.88% (F12.5/T1). Numerous CD45-positive cells
      were also observed in both F25/T4 and F12.5/T1 combinations. CONCLUSION(S): The
      present study is the first to show survival and growth of isolated murine ovarian
      follicles 1 week after autotransplantation of isolated OCs in a fibrin scaffold.
      The results indicate that fibrin is a promising candidate as a matrix for the
      construction of an artificial ovary. Xenotransplantation of isolated human
      follicles and OCs is the necessary next step to validate these findings.

PMID- 24462060
TI  - In vitro effects of coital lubricants and synthetic and natural oils on sperm
      motility.
AB  - OBJECTIVE: To evaluate the effects of coital lubricants and oils on sperm
      motility. DESIGN: Comparative prospective in vitro study. SETTING: University
      Andrology laboratory. PATIENT(S): Twenty-two normozoospermic donors.
      INTERVENTION(S): Semen samples were incubated in modified human tubal fluid
      (mHTF) control and in 10% Pre-Seed, Astroglide, and KY products (Sensitive,
      Warming, and Tingling) and baby, canola, sesame, and mustard oils. Total and
      progressive sperm motility was evaluated before and at 5, 30, and 60 minutes of
      incubation. MAIN OUTCOME MEASURE(S): Sperm motility. RESULT(S): Control samples
      exhibited no significant decrease in sperm motility. Pre-Seed showed a slight
      (~4%) but significant drop in progressive motility after 30 minutes. Total and
      progressive sperm motility significantly declined under Astroglide, KY products
      (Sensitive, Warming, and Tingling) and sesame oil incubation. Canola oil
      significantly decreased total motility after 30 minutes and progressive motility
      after 5 minutes of incubation. Similarly, baby oil decreased total motility after
      60 minutes and progressive motility after 5 minutes. After initial decline, total
      and progressive sperm motility under Pre-Seed and canola and baby oils remained
      high. Exposure to mustard oil caused persistent hyperactivation of sperm in each
      sample with no decrease in motility. CONCLUSION(S): Sesame oil and synthetic
      coital lubricants impaired sperm motility and may hamper fertility. Pre-Seed and
      canola, mustard, and baby oils showed no deleterious effect and may be considered
      sperm-friendly coital lubricants. Mustard oil exposure resulted in
      hyperactivation of sperm and needs to be studied further.

PMID- 24462061
TI  - Development of a high-resolution Y-chromosome microarray for improved male
      infertility diagnosis.
AB  - OBJECTIVE: To develop a novel clinical test using microarray technology as a high
      resolution alternative to current methods for detection of known and novel
      microdeletions on the Y chromosome. DESIGN: Custom Agilent 8x15K array
      comparative genomic hybridization (aCGH) with 10,162 probes on an average probe
      spacing of 2.5 kb across the euchromatic region of the Y chromosome. SETTING:
      Clinical diagnostic laboratory. PATIENT(S): Men with infertility (n = 104) and
      controls with proven fertility (n = 148). INTERVENTION(S): Microarray genotyping
      of DNA. MAIN OUTCOME MEASURE(S): Gene copy number variation determined by log
      ratio of probe signal intensity against a DNA reference. RESULT(S): Our aCGH
      experiments found all known AZF microdeletions as well as additional unbalanced
      structural alterations. In addition to complete AZF microdeletions, we found that
      AZFc partial deletions represent a risk factor for male infertility. In total,
      aCGH-based detection achieved a diagnostic yield of ~11% and also revealed
      additional potentially etiologic copy number variations requiring further
      characterization. CONCLUSION(S): The aCGH approach is a reliable high-resolution
      alternative to multiplex polymerase chain reaction for the discovery of
      pathogenic chromosome Y microdeletions in male infertility.

PMID- 24462062
TI  - Goserelin fosters bone elongation but does not prevent ovarian damage in
      cyclophosphamide-treated prepubertal mice.
AB  - OBJECTIVE: To evaluate whether administration of goserelin, a gonadotropin
      releasing hormone (GnRH) agonist, could prevent acute or chronic ovarian
      insufficiency from cyclophosphamide (CTX) administration to prepubertal mice.
      DESIGN: Animal study. SETTING: University center. ANIMAL(S): C57BL/6J mouse
      strain. INTERVENTION(S): Goserelin administered on day 13 of life, CTX on day 18
      of life, euthanasia on day 20 (prepubertal), 56 (pubertal), or 92 of life
      (mature), measurements of body weight, length, uterine weight, serum
      antimullerian hormone and follicle-stimulating hormone, and histologic assessment
      of ovarian follicles and femur growth, and apoptotic rates by TUNEL. MAIN OUTCOME
      MEASURE(S): Assessment of prevention of ovarian insufficiency and defective bone
      elongation from CTX administration. RESULT(S): Prepubertal mice were randomly
      assigned to three groups: control (G1), CTX (G2), and goserelin + CTX (GG). A
      total of 63 mice were euthanized in the three groups. Body weight and length, and
      uterine weight did not differ among groups at any age. Ovarian size was not
      different in the three groups. There were fewer primordial and primary
      follicles/mm(2) in groups GG and G2 than in group G1 at all ages, but there was
      no difference between groups GG and G2. Corpora lutea/mm(2) were decreased in
      group GG versus G2. Femur length was statistically significantly greater in
      groups G1 and GG than group G2. CONCLUSION(S): Goserelin administered to
      prepubertal mice during CTX treatment fosters maintenance of bone elongation but
      does not protect the ovaries from follicular depletion.

PMID- 24462063
TI  - Effect of sugar molecules on the cryopreservation of mouse spermatogonial stem
      cells.
AB  - OBJECTIVE: To study the influence of sugars and establish a serum-free freezing
      method for the cryopreservation of spermatogonial stem cells (SSCs). DESIGN:
      Animal study. SETTING: University laboratory. ANIMAL(S): C57BL/6-TgEGFP, C57BL/6
      mice. INTERVENTION(S): Germ cells enriched from testis cells were frozen using
      standard freezing medium containing sugars, including monosaccharides,
      disaccharides, and trisaccharides at 50, 100, and 200 mM, respectively. To study
      the feasibility of establishing a serum-free freezing method, fetal bovine serum
      was substituted with knockout serum replacement. MAIN OUTCOME MEASURE(S): Freeze
      thawed germ cells were evaluated for recovery rate, proliferation capacity, and
      stem cell activity after transplantation to recipient testes. RESULT(S):
      Supplementation of freezing medium with 200 mM disaccharide is an effective
      method for cryopreservation of SSCs. Trehalose is the most effective
      cryoprotectant among all the sugars tested and only lactose was comparable to
      trehalose. Our proliferation and transplantation data show that serum-free
      freezing can be achieved in freezing medium supplemented with 200 mM trehalose,
      10% knockout serum replacement, and 10% dimethyl sulfoxide (DMSO) for
      cryopreservation of SSCs. CONCLUSION(S): These findings raise the possibility of
      effectively banking frozen SSCs from various species, including humans, in a
      traditional serum-free medium for germ cell research and male infertility
      treatments.

PMID- 24462064
TI  - Impact of increased orifice size and decreased flow velocity of left atrial
      appendage on stroke in nonvalvular atrial fibrillation.
AB  - The structural and functional characteristics of left atrial appendage (LAA) in
      patients with atrial fibrillation (AF) with previous stroke remain incompletely
      elucidated. This study investigated whether a larger LAA orifice is related to
      decreased LAA flow velocity and stroke in nonvalvular AF. The dimension,
      morphology, and flow velocity of LAA were compared in patients with nonvalvular
      AF with (stroke group, n = 67, mean age 66 +/- 9 years) and without ischemic
      stroke (no-stroke group, n = 151, mean age 56 +/- 10 years). Compared with no
      stroke group, the stroke group had larger LA dimension (4.7 +/- 0.8 vs 4.2 +/-
      0.6 cm, p <0.001), larger LAA orifice area (4.5 +/- 1.5 vs 3.0 +/- 1.1 cm(2), p
      <0.001), and slower LAA flow velocity (36 +/- 19 vs 55 +/- 20 cm/s, p <0.001).
      LAA flow velocity was negatively correlated with LAA orifice size (R = -0.48, p
      <0.001). After adjustment for multiple potential confounding factors including
      CHA2DS2-VASc score, persistent AF, and LA dimension, large LAA orifice area (odds
      ratio 6.16, 95% confidence interval 2.67 to 14.18, p <0.001) and slow LAA
      velocity (odds ratio 3.59, 95% confidence interval 1.42 to 9.08, p = 0.007) were
      found to be significant risk factors of stroke. In patients with LAA flow
      velocity <37.0 cm/s, patients with large LAA orifice (>3.5 cm(2)) had greater
      incidence of stroke than those with LAA orifice of <=3.5 cm(2) (75% vs 23%, p
      <0.001). In conclusion, LAA orifice enlargement was related to stroke risk in
      patients with nonvalvular AF even after adjustment for other risk factors, and it
      could be the cause of decreased flow velocity in LAA.

PMID- 24462065
TI  - Relation of reduced expression of MiR-150 in platelets to atrial fibrillation in
      patients with chronic systolic heart failure.
AB  - Atrial fibrillation (AF) is associated with poor prognosis in patients with heart
      failure (HF). Although platelets play an important role in rendering a
      prothrombotic state in AF, the exact mechanism by which the effect is mediated is
      still debated. MicroRNAs (miRNAs), which have been shown to be involved in a
      variety of cardiovascular conditions, are abundant in platelets and in a cell
      free form in the circulation. In the present study, we performed a genome-wide
      screen for miRNA expression in platelets of patients with systolic HF and in
      controls without cardiac disease, in pursuit of specific miRNAs that are
      associated with the presence of AF. MiRNA expression was measured in platelets
      from 50 patients with systolic HF and 50 controls, of which, samples from 41
      patients with HF and 35 controls were used in the final analysis because of a
      quality control process. MiR-150 expression was 3.2-fold lower (p = 0.0003) in
      platelets of patients with HF with AF relative to those without AF. A similar
      effect was seen in serum samples from the same patients, in which miR-150 levels
      were 1.5-fold lower (p = 0.004) in patients with HF with AF. Furthermore, the
      serum levels of miR-150 were correlated to platelet levels in patients with AF (r
      = 0.65, p = 0.0087). In conclusion, miR-150 expression levels in platelets of
      patients with systolic HF with AF are significantly reduced and correlated to the
      cell-free circulating levels of this miRNA.

PMID- 24462066
TI  - Frequency, pattern, and cause of fever following transfemoral transcatheter
      aortic valve implantation.
AB  - Fever after transcatheter aortic valve implantation (TAVI) is common and may
      result in extensive workup, treatment with broad-spectrum antibiotics, and
      prolonged hospitalization. Despite these consequences, the prevalence and nature
      of fever after TAVI and whether cases of fever could be attributed to an
      infectious origin have not been studied thoroughly to date. We conducted an
      observational retrospective analysis of 148 consecutive patients undergoing
      percutaneous transfemoral TAVI at the Tel-Aviv Medical Center. All patients were
      treated with antibiotic prophylaxis using first- or second-generation
      cephalosporins (or vancomycin upon a beta-lactam allergy) on the procedure day.
      Medical and nursing records were reviewed for the occurrence, extent, and origin
      of fever. Laboratory databases were screened for positive cultures. Fever >=37.5
      degrees C occurred in 66 patients (47%) and >=38.0 degrees C in 27 patients
      (19.4%). Most febrile episodes >=38.0 degrees C were of short duration, lasting
      <8 hours (59.3%, n = 16), and occurred in the first 48 hours after procedure
      (74%, n = 22). Bacteremia was found in 2 cases and urinary tract infection in 3
      other cases; most pathogens isolated were resistant to prophylactic antibiotic
      regimen. Unlike prolonged fever, a short febrile episode was not associated with
      an extended hospital stay or with increased 30-day mortality rate after TAVI. In
      conclusion, fever after TAVI occurs frequently and may represent a noninfectious
      inflammatory response as it rarely associates with a documented bacterial
      infection. Therefore, deferring antibiotic therapy in an otherwise well post-TAVI
      patient with a short febrile episode should be considered, whereas prolonged and
      high-grade fever warrants further workup and empirical antibiotic therapy.

PMID- 24462067
TI  - Meta-analysis of the quantitative relation between pulse pressure and mean
      arterial pressure and cardiovascular risk in patients with diabetes mellitus.
AB  - Results of epidemiologic studies that investigated the significance of pulse
      pressure (PP) and mean arterial pressure (MAP) in terms of risk of cardiovascular
      disease (CVD) in patients with diabetes mellitus are inconsistent. We performed a
      quantitative meta-analysis to estimate CVD risk in relation to PP or MAP.
      Electronic literature search was conducted for prospective studies providing data
      on CVD risk for an increment in baseline MAP or PP in patients with diabetes
      mellitus. The pooled CVD risk for a 10-mm Hg increase in each blood pressure (BP)
      index was estimated with a random-effects model. There were 17 eligible studies
      consisting of 52,647 patients and 5,112 CVD cases. The pooled relative risk (95%
      confidence interval) of CVD for an increment of 10 mm Hg was 1.10 (1.04 to 1.16)
      for PP and 1.09 (0.98 to 1.21) for MAP. Significant between-study heterogeneity
      was observed (I(2) [p value]; 76.5% [p <0.001] for PP, 67.8% [p = 0.005] for
      MAP). In studies concurrently investigating CVD risk for the 4 indexes (i.e., PP,
      MAP, systolic BP, and diastolic BP), the pooled relative risk (95% confidence
      interval) was 1.17 (1.09 to 1.26) for PP, 1.11 (1.06 to 1.15) for MAP, 1.14 (1.06
      to 1.22) for systolic BP, and 1.06 (0.94 to 1.19) for diastolic BP. In
      conclusion, the current meta-analysis suggested that PP was the strongest
      indicator among the 4 commonly used BP indexes. However, the large heterogeneity
      urged cautious interpretation of the study results.

PMID- 24462068
TI  - Effect of preoperative obstructive sleep apnea on the frequency of atrial
      fibrillation after coronary artery bypass grafting.
AB  - Patients with obstructive sleep apnea (OSA) have intermittent hypoxia leading to
      atrial remodeling and this has been associated with the development of atrial
      fibrillation (AF). Postoperative AF is a common complication of coronary artery
      bypass grafting (CABG). The aim of this prospective study was to determine
      whether the presence of OSA predicts the occurrence of post-CABG AF (PCAF). This
      was a prospective single-center study. Patients undergoing elective CABG were
      evaluated and categorized as confirmed, high-risk, or low-risk OSA according to a
      modified Berlin questionnaire. PCAF was evaluated by 24-hour cardiac monitoring
      strip or 12-lead electrocardiography during the postoperative period, and
      validated by an electrophysiologist. We included 277 patients. OSA prevalence was
      47.7%, with body mass index (31.0 vs 26.9 kg/m(2), p <=0.001), advanced age (63.7
      vs 66.4 years, p = 0.031), hypertension (78.0% vs 64.8%, p = 0.015), and diabetes
      (45.5% vs 28.3%, p = 0.003) more prevalent in the OSA group. PCAF was found to
      occur in 37.2% of all patients and OSA was found to be a strong predictor of PCAF
      (45.5% vs 29.7%, p = 0.007). PCAF was also associated with continuous positive
      airway pressure use (12.6% vs 5.2%, p = 0.027). Increased length of stay was
      associated with PCAF (6.5 vs 5.3 days, p = 0.006), as was longer time from
      surgery to occurrence of PCAF (p = 0.001). In conclusion, OSA was found to be a
      strong predictor of PCAF, which in turn was found to be associated with increased
      length of stay.

PMID- 24462069
TI  - Left ventricular mass in children and adolescents with elevated body mass index
      and normal waist circumference.
AB  - Children and adolescents with elevated body mass index (BMI) who have normal
      waist circumference (NWC) have a cardiometabolic risk profile similar to normal
      children. However, there is a lack of adequate information regarding their left
      ventricular mass (LVM). The present study was undertaken to evaluate LVM in
      children with elevated BMI with NWC. LVM was assessed by echocardiography in 247
      children (age 2 to 19 years) without evidence of heart disease. Data on those who
      had elevated BMI with NWC (group 1, n = 80) were compared with matched normal
      controls with normal BMI who had NWC (group 2, n = 80) and children with elevated
      BMI with increased waist circumference (IWC; group 3, n = 87). Correlations, t
      tests, and linear regressions were used for statistical testing. LVM in children
      with elevated BMI with NWC was not significantly different from normal controls
      (97.6 +/- 44.4 vs 100.7 +/- 47.9 g, p = 0.6713, respectively); however, it was
      significantly less than that in subjects with elevated BMI who also had IWC (97.6
      +/- 44.4 vs 114.5 +/- 47.8 g, p = 0.0193, respectively). Similar to normal
      controls, those subjects with elevated BMI with NWC had a stronger correlation
      between LVM and lean body mass (R(2) = 0.86 and 0.86, respectively) than subjects
      with elevated BMI with IWC (R(2) = 0.75). In conclusion, children with elevated
      BMI with NWC appear to have a similar LVM profile as children with normal BMI
      with NWC. The present study emphasizes the importance of measuring waist
      circumference in children with elevated BMI.

PMID- 24462070
TI  - Effect of cardiac resynchronization therapy on the sequence of mechanical
      activation assessed by two-dimensional radial strain imaging.
AB  - Cardiac resynchronization therapy (CRT) induces left ventricular (LV) reverse
      remodeling by synchronizing LV mechanical activation. We evaluated changes in
      segmental LV activation after CRT and related them to CRT response. A total of
      292 patients with heart failure (65 +/- 10 years, 77% men) treated with CRT
      underwent baseline echocardiographic assessment of LV volumes and ejection
      fraction. Time-to-peak radial strain was measured for 6 midventricular LV
      segments with speckle-tracking strain imaging. Moreover, the time difference
      between the peak radial strain of the anteroseptal and the posterior segments was
      calculated to obtain LV dyssynchrony. After 6 months, LV volumes, segmental LV
      mechanical activation timings, and LV dyssynchrony were reassessed. Response to
      CRT was defined as >=15% decrease in LV end-systolic volume at 6-month follow-up.
      Responders (n = 177) showed LV resynchronization 6 months after CRT (LV
      dyssynchrony from 200 +/- 127 to 85 +/- 86 ms; p <0.001) by earlier activation of
      the posterior segment (from 438 +/- 141 to 394 +/- 132 ms; p = 0.001) and delayed
      activation of the anteroseptal segment (from 295 +/- 155 to 407 +/- 138 ms; p
      <0.001). In contrast, nonresponders (n = 115) experienced an increase in LV
      dyssynchrony 6 months after CRT (from 106 +/- 86 to 155 +/- 112 ms; p = 0.001)
      with an earlier activation of posterior wall (from 391 +/- 139 to 355 +/- 136 ms;
      p = 0.039) that did not match the delayed anteroseptal activation (from 360 +/-
      148 to 415 +/- 122 ms; p = 0.001). In conclusion, responders to CRT showed LV
      resynchronization through balanced lateral and anteroseptal activations. In
      nonresponders, LV dyssynchrony remains, by posterior wall preactivation and
      noncompensatory delayed septal wall activation.

PMID- 24462071
TI  - Right ventricular morphology and systolic function in left ventricular
      noncompaction cardiomyopathy.
AB  - The distinction between normal right ventricular (RV) trabeculations from
      abnormal has been difficult. We evaluated whether RV volume and function are
      related to left ventricular (LV) noncompaction (NC) cardiomyopathy and clinical
      events. Trabeculations or possible LVNC by cardiac magnetic resonance imaging was
      retrospectively observed among 105 consecutive cases. We measured LV end-systolic
      (ES) noncompacted-to-compacted ratio, RV ejection fraction (EF), RV apical
      trabecular thickness, and RV end-diastolic (ED) noncompacted-to-compacted ratio.
      A control group of 40 subjects was also reviewed to assess the exploratory
      measures. Comparing those with LVES noncompacted-to-compacted ratio >=2, those
      with LVES noncompacted-to-compacted ratio <2, and the normal control group,
      adjusted means for RV apical trabecular thickness and RVED noncompacted-to
      compacted ratio were generated. Logistic regression was used to evaluate the
      association of composite events traditionally associated with LVNC with RVEF
      after adjustment for aforementioned covariates, cardiovascular risk factors,
      delayed enhancement, LVEF, and LVES noncompacted-to-compacted ratio. Analysis of
      RV morphology found greater apical trabecular thickness among those with LVES
      noncompacted-to-compacted ratio >=2 compared with those with LVES noncompacted-to
      compacted ratio <2 or normal control group (31 +/- 5 vs 27 +/- 2.6 vs 22 +/- 4
      mm; p = 0.03 and p = 0.003, respectively). There was no difference between the
      groups in relation to the RVED noncompacted-to-compacted ratio. Low RVEF and LVES
      noncompacted-to-compacted ratio >=2 had significant association with clinical
      events in this population even after adjusting for clinical and imaging
      parameters (p = 0.04 and p <0.001, respectively). In conclusion, RV dysfunction
      in a morphologic LVNC population is strongly associated with adverse clinical
      events. LVNC is associated with increased trabeculations of the RV apex.

PMID- 24462072
TI  - Asymptomatic sinus bradycardia following bariatric surgery.
AB  - Approximately 121,000 bariatric surgical procedures are performed annually, and
      salutary effects include a reduction in cardiovascular morbidity and mortality,
      risk factor modification, and improvement in sympathovagal tone. There are
      anecdotal accounts of unexplained sinus bradycardia (SB) after significant weight
      loss but no systematic studies have been conducted. The purpose of this study was
      to determine the frequency of incident SB, its timing, and association with
      weight loss, clinical characteristics, and predictors. We evaluated various
      clinical characteristics including resting heart rate, blood pressure, body mass
      index (BMI), heart rate reserve (HRR), basal metabolic rate, and exercise regimen
      in 151 consecutive patients who underwent bariatric surgery. Multiple logistic
      regression analysis was performed to determine predictors of SB. Twenty-five of
      137 patients (18%) experienced postoperative SB. Patients with SB had
      significantly greater reduction in BMI than those without bradycardia (35 +/-
      9.6% and 25.7 +/- 13%, respectively, p = 0.002). HRR was significantly greater in
      patients with SB (116 +/- 14 beats/min) compared with those without bradycardia
      (105 +/- 14 beats/min, p = 0.007). Multiple logistic regression analysis revealed
      that the odds of developing SB were 1.96 and 1.91 and associated with the percent
      decrease in BMI (95% confidence interval 1.3 to 3.0, p = 0.002) or increase in
      HRR (95% confidence interval 1.28 to 2.85, p = 0.002), respectively. In
      conclusion, SB occurred 14 +/- 11 months postoperatively and its predictors were
      the percent reduction in BMI or increase in HRR.

PMID- 24462073
TI  - Influence of high-dose highly efficient statins on short-term mortality in
      patients undergoing percutaneous coronary intervention with stenting for acute
      coronary syndromes.
AB  - Statins are recommended for prevention of progression of cardiovascular disease
      after percutaneous coronary intervention (PCI). Although high-dose highly
      efficient statins are recommended, especially in high-risk patients, clinical
      data are scarce and further investigation in "real-world" settings is needed. One
      thousand five hundred twenty-eight consecutive patients, who underwent PCI for
      acute coronary syndrome, were included in a prospective registry from January
      2003 to January 2011. In post hoc analysis, cardiovascular risk factors, co
      morbidities, and circulating lipid parameters at the time of intervention were
      evaluated. As a primary end point, all-cause mortality after a follow-up period
      of 3 months was investigated. Results were compared between patients receiving
      high-dose highly effective statins (atorvastatin 80 mg or rosuvastatin 20 mg)
      versus patients receiving low-dose statins or who were without lipid-lowering
      therapy at the time of discharge. Nine hundred twenty-six patients (60.6%)
      received high-dose atorvastatin or rosuvastatin and 602 patients (39.4%) received
      low-dose statin therapy or were not on statins at discharge. Eight patients
      (0.9%) receiving high-dose statin therapy and 21 patients (3.5%) taking low-dose
      statins or no statins at discharge died during the 3-month follow-up (hazard
      ratio 0.244, 95% confidence interval 0.108 to 0.551, p=0.001). After propensity
      score adjustment the results remained significant (adjusted hazard ratio for high
      dose statins 0.405, 95% confidence interval 0.176 to 0.931, p=0.033). In
      conclusion, in this single-center series of 1,528 real-world patients undergoing
      PCI for acute coronary syndrome, a significant reduction in short-term all-cause
      mortality could be demonstrated in patients receiving high-dose highly efficient
      statins compared with patients receiving low-dose statins or no lipid-lowering
      therapy.

PMID- 24462074
TI  - A new preoperative prognostic scoring system to predict prognosis in patients
      with locally advanced pancreatic body cancer who undergo distal pancreatectomy
      with en bloc celiac axis resection: a retrospective cohort study.
AB  - BACKGROUND: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR)
      provides good local control for locally advanced pancreatic body cancer, but
      early recurrence still occurs. In this study, we aimed to establish a new scoring
      system to predict prognosis using preoperative factors in patients with locally
      advanced pancreatic body cancer who undergo DP-CAR. METHODS: Prognostic factors
      were analyzed using various data collected retrospectively from 50 consecutive
      patients who underwent DP-CAR. Using these preoperative factors, a scoring system
      to predict prognosis was established. RESULTS: Multivariate analysis identified
      intraoperative blood loss (>=940 mL; hazard ratio [HR], 25.179; P = .0003),
      preoperative platelet counts (<150 * 10(9)/L; HR, 7.433; P = .0043), preoperative
      C-reactive protein (CRP) levels (>=0.4 mg/dL; HR, 7.064; P = .0018), and
      preoperative carbohydrate antigen 19-9 (CA19-9) levels (>=300 U/mL; HR, 8.197; P
      = .0053) as independent adverse prognostic factors. For the 3 preoperative
      factors, preoperative platelet counts <150 * 10(9)/L, preoperative CRP levels
      >=0.4 mg/dL, and preoperative CA19-9 levels >=300 U/mL were allocated 1 point
      each. The total score was defined as the Preoperative Prognostic Score (PPS). The
      estimated disease-specific 1- and 5-year survival rates for the 26 patients with
      PPS0 were 95.7%, and 49.1%, respectively, and for the 15 patients with PPS1, they
      were 86.7% and not available, respectively. The median survival times for PPS0
      and PPS1 were 50.6 and 22.3 months, respectively. In contrast, in the 9 patients
      with PPS2/3, 1- and 5-year survival rates were 33.3% and 0%, respectively, and
      median survival time was only 7.7 months. CONCLUSION: A new prognostic scoring
      system using the preoperative platelet count, CRP, and CA19-9 enables
      preoperative prediction of prognosis and facilitates selection of appropriate
      treatment for borderline resectable cases of locally advanced pancreatic body
      cancer.

PMID- 24462075
TI  - Comment on "predicting aggressive behavior in nonfunctioning pancreatic
      neuroendocrine".

PMID- 24462076
TI  - Comment on "peroral esophageal myotomy (POEM) and laparoscopic Heller myotomy
      produce a similar short-term anatomic and functional effect".

PMID- 24462077
TI  - An independent jury-based consensus conference model for the development of
      recommendations in medico-surgical practice.
AB  - BACKGROUND: There is an increasing demand for standardization in the choice of
      treatments for specific conditions, so-called personalized medicine. The task is
      far from trivial, because the perspectives from many stakeholders must be
      respected, including patients and health care providers, as well as payers or
      governments to better control costs while optimizing quality of care. One
      approach to provide widely accepted therapies is the consensus conference.
      METHODS: We describe a novel methodology to achieve consensus in controversial
      areas with the main goal to minimize biases. RESULTS: The principle of this
      approach relies on a clear distinction between those who provide the evidence
      (experts) and those who draw the final recommendations (the jury). The jury
      consists of individuals with sufficient background knowledge to cover the
      perspectives of all stakeholders' without being involved directly in the topic
      under evaluation. The organizing committee, the experts, and the jury interact
      within 3 phases: Preparation, the actual consensus conference, and deliberations.
      Each question is addressed by a panel of experts, leading to the proposition of
      recommendations at the conference meeting, which are challenged by the jury and
      the audience. Based on all available information, the jury finalizes the
      consensus recommendations, which are eventually published and made available to
      all. CONCLUSION: This novel model of consensus conference allows the construction
      of consensual, evidence-based, explicit recommendations for therapies in a
      process that may also identify issues for further research, eventually fostering
      progress in the field.

PMID- 24462078
TI  - Use of a temporary intraoperative mesentericoportal shunt for pancreatic
      resection for locally advanced pancreatic cancer with portal vein occlusion and
      portal hypertension.
AB  - BACKGROUND: Our aim was to evaluate the perioperative morbidity and survival of a
      selected group of patients with locally advanced pancreatic ductal adenocarcinoma
      (PDAC) and malignant obstruction of portal axis inducing portal hypertension (PH)
      who underwent a curative intent pancreatic resection, after neoadjuvant
      chemotherapy, adopting a new type of temporary intraoperative mesentericoportal
      shunt (TMPS). METHODS: We analyzed the perioperative data and survival outcome of
      15 patients with locally advanced PDAC and PH who underwent pancreatoduodenectomy
      combined with vascular resections between October 2008 and October 2012 using
      this TMPS. RESULTS: There was no perioperative mortality. Postoperative morbidity
      occurred in 7 patients without any postoperative liver failure. All patients
      underwent mesentericoportal venous resection, 11 of whom had a concomitant
      arterial resection. The mean +/- SD follow-up was 16 +/- 10 months (range, 4-40;
      median 15). Overall survival rates of patients were 78% and 11% at 1 and at 3
      years, respectively. Median survival was 17 months. The 1-year disease-free
      survival was 36%. CONCLUSION: The use of this form of TMPS allowed us to achieve
      PD or total pancreatectomy in patients with locally advanced PDAC and PH without
      postoperative mortality but with increased morbidity. The relevance of such an
      aggressive approach is yet to be determined.

PMID- 24462079
TI  - Cold exposure--an approach to increasing energy expenditure in humans.

PMID- 24462080
TI  - Statins: protectors or pretenders in prostate cancer?
AB  - The role of statin therapy in prostate cancer (PCa) prevention and treatment is
      plagued by controversy. This critical review of published clinical series reveals
      several caveats in earlier studies, which reported no benefit. Recent studies
      that adjust for confounding factors have demonstrated statin therapy to be
      associated with PCa prevention and favorable clinical outcomes. Developed as
      inhibitors of cholesterol synthesis, the expected mechanism of statin action is
      systemic cholesterol reduction. By lowering circulating cholesterol, statins
      indirectly reduce cellular cholesterol levels in multiple cell types, impacting
      on membrane microdomains and steroidogenesis. Although non-cholesterol mechanisms
      of statin action have been proposed, they are limited by the uncertainties
      surrounding in vivo tissue statin concentrations. 

PMID- 24462081
TI  - Identification and quantification of known polycyclic aromatic hydrocarbons and
      pesticides in complex mixtures using fluorescence excitation-emission matrices
      and parallel factor analysis.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and pesticides are among the most
      widespread organic contaminants in aquatic environments. Because of their
      aromatic structure, PAHs and pesticides have intrinsic fluorescence properties in
      the ultraviolet/blue spectral range. In this study, excitation-emission matrix
      (EEM) fluorescence spectroscopy and parallel factor (PARAFAC) analysis were used
      to characterise and discriminate fluorescence signatures of nine PAHs and three
      pesticides at the MUg L(-1) level in the presence of humic substances (0.1-10
      mgCL(-1)). These contaminants displayed a diversity of fluorescence signatures
      regarding spectral position (lambdaEx: 220-335 nm, lambdaEm: 310-414 nm), Stokes
      shift (39-169 nm) and number of peaks (1-8), with detection limits ranging from
      0.02 to 1.29MUgL(-1). The EEM/PARAFAC method applied to mixtures of PAHs with
      humic substances validated a seven-component model that included one humic-like
      fluorophore and six PAH-like fluorophores. The EEM/PARAFAC method applied to
      mixtures of pesticides with humic substances validated a six-component model that
      included one humic-like fluorophore and three pesticide-like fluorophores. The
      EEM/PARAFAC method adequately quantified most of the contaminants for humic
      substance concentrations not exceeding 2.5 mg CL(-1). The application of this
      method to natural (marine) samples was demonstrated through (1) the match between
      the Ex and Em spectra of PARAFAC components and the Ex and Em spectra of standard
      PAHs, and (2) the good linear correlations between the fluorescence intensities
      of PARAFAC components and the PAH concentrations determined by GC-MS.

PMID- 24462082
TI  - Inhibition of the nitrification process in activated sludge by trivalent and
      hexavalent chromium, and partitioning of hexavalent chromium between sludge
      compartments.
AB  - The input of wastewater treatment plants (WWTPs) may contain high concentrations
      of Cr(III) and Cr(VI), which can affect nitrogen removal. In the present study
      the influence of different Cr(III) and Cr(VI) concentrations towards activated
      sludge nitrification was studied. To better understand the mechanisms of Cr(VI)
      toxicity, its reduction, adsorption and uptake in activated sludge was
      investigated in a batch growth system. Quantification of Cr(VI) was performed by
      speciated isotope dilution inductively coupled plasma mass spectrometry. It was
      found that Cr(VI) concentrations above 1.0 mg L(-1) and Cr(III) concentrations
      higher than 50 mg L(-1) negatively affected nitrification. Speciation studies
      indicated almost complete reduction of Cr(VI) after 24h of incubation when Cr(VI)
      concentrations were lower than 2.5 mg L(-1), whereas for Cr(VI) added to 5 mg L(
      1) around 40% remained unreduced. The study of the partitioning of Cr in the
      activated sludge was performed by the addition of Cr(VI) in concentrations of 2.5
      and 5.0 mg L(-1). Results revealed that Cr was allocated mainly within the
      intercellular compartments, whereas intracellular and adsorbed Cr represented
      less than 0.1% of the Cr sludge concentrations. Cr(VI) was reduced in all
      compartments, the most efficiently (about 94%) within the intracellular and
      intercellular fractions. The extent of reduction of adsorbed Cr was 92% and 80%
      for 2.5 and 5.0mg of Cr(VI) L(-1), respectively. The results of present
      investigation provide a new insight into the toxicity of Cr species towards
      activated sludge nitrification, which is of significant importance for the
      management of WWTPs in order to prevent them from inflows containing harmful
      Cr(VI) concentrations.

PMID- 24462083
TI  - Potential microbial toxicity and non-target impact of different concentrations of
      glyphosate-containing herbicide (GCH) in a model Pervious Paving System.
AB  - Pervious Pavement Systems are Sustainable Drainage devices that meet the three
      fold SUDS functions of stormwater quantity reduction, quality improvement and
      amenity benefits. This paper reports on a study to determine the impact of
      different concentrations of glyphosate-containing herbicides on non-target
      microorganisms and on the pollutant retention performance of PPS. The experiment
      was conducted using 0.0484 m(2) test rigs based on a four-layered design.
      Previous studies have shown that PPS can trap up to 98.7% of applied
      hydrocarbons, but results of this study show that application of glyphosate
      containing herbicides affected this capability as 15%, 9% and 5% of added
      hydrocarbons were released by high (7200 mg L(-1)), medium (720 mg L(-1)) and low
      (72 mg L(-1)) glyphosate-containing herbicides concentrations respectively. The
      concentrations of nutrients released also indicate a potential for eutrophication
      if these effluents were to infiltrate into aquifers or be released into surface
      waters. The effect of glyphosate-containing herbicides application on the
      bacterial and fungal communities was slightly different; fungi exhibited a "top
      down" trend as doses of 7200 mg L(-1) glyphosate-containing herbicides yielded
      the highest fungal growth whilst those with a concentration of 720 mg L(-1)
      glyphosate-containing herbicides applied yielded the highest bacterial growth. In
      the case of protists, doses of glyphosate-containing herbicides above 72 mg L(-1)
      were fatal, but they survived at the lower concentration, especially the ciliates
      Colpoda cucullus and Colpoda steinii thus indicating potential for their use as
      biomarkers of herbicide-polluted environments. Data also showed that at the
      lowest concentration of glyphosate-containing herbicides (72 mg L(-1)),
      biodegradation processes may not be affected as all trophic levels required for
      optimum biodegradation of contaminants were present.

PMID- 24462084
TI  - Micro-mechanism and rate constants for OH-initiated degradation of methomyl in
      atmosphere.
AB  - The atmospheric degradation reactions of the two isomers of methomyl (MTL)
      initiated by OH radical in the presence of O2, NO and H2O have been investigated
      by density functional theory (DFT). The calculations were all carried out at
      MPWB1K level. The geometrical parameters and vibrational frequencies of
      stationary points were calculated with 6-31+G (d, p) basis sets. Single-point
      energy calculations were performed with 6-311+G (3df, 2p) basis sets. Profiles of
      the potential energy surface were constructed and all possible channels involved
      in the reactions were discussed. The rate constants of main elementary reactions
      were calculated over a temperature range of 200-400 K and mostly fitted to
      Arrhenius formulas. The atmospheric lifetimes of reaction species were discussed
      for the first time, which can be applied to the study on model simulation and
      management of hazardous materials.

PMID- 24462085
TI  - Barium recovery by crystallization in a fluidized-bed reactor: effects of pH,
      Ba/P molar ratio and seed.
AB  - The effects of process conditions, including upward velocity inside the column,
      the amount of added seed and seed size, the pH value of the precipitant or the
      phosphate stream and the Ba/P molar ratio in a fluidized-bed reactor (FBR) were
      studied with a view to producing BaHPO4 crystals of significant size and maximize
      the removal of barium. XRD were used to identify the products that were collected
      from the FBR. Experimental results show that an upward velocity of 48 cmmin(-1)
      produced the largest BaHPO4 crystals with a size of around 0.84-1.0mm. The
      addition of seed crystals has no effect on barium removal. The use of a seed of a
      size in the ranges unseeded<0.149-0.29 mm<0.149 mm<0.29-0.42 mm produced
      increasing amounts of increasingly large crystals. The largest BaHPO4 crystals
      were obtained at pH 8.4-8.8 with a Ba/P molar ratio of 1.0. In the homogeneous
      and heterogeneous processes, around 98% of barium was removed at pH 8.4-8.6 and
      [Ba]/[P]=1.0. The XRD results show that a significant amount of barium phosphate
      (Ba3(PO4)2) was obtained at pH 11. The compounds BaHPO4 and BaO were present at a
      pH of below 10.

PMID- 24462086
TI  - Essence of disposing the excess sludge and optimizing the operation of wastewater
      treatment: rheological behavior and microbial ecosystem.
AB  - Proper disposal of excess sludge and steady maintenance of the high bioactivity
      of activated sludge in bioreactors are essential for the successful operation of
      wastewater treatment plants (WWTPs). Since sludge is a non-Newtonian fluid, the
      rheological behavior of sludge can therefore have a significant impact on various
      processes in a WWTP, such as fluid transportation, mixing, oxygen diffusion, mass
      transfer, anaerobic digestion, chemical conditioning and mechanical dewatering.
      These are key factors affecting the operation efficiency and the energy
      consumption of the entire process. In the past decade-due to the production of
      large quantities of excess sludge associated with the extensive construction of
      WWTPs and the emergence of some newly-developed techniques for wastewater
      purification characterized by high biomass concentrations-investigations into the
      rheology of sludge are increasingly important and this topic has aroused
      considerable interests. We reviewed a number of investigations into the rheology
      of sludge, with the purpose of providing systematic and detailed analyses on the
      related aspects of the rheological behavior of sludge. It is clear that, even
      though considerable research has focused on the rheology of sludge over a long
      time period, there is still a need for further thorough investigation into this
      field. Due to the complex process of bio-treatment in all WWTPs, biological
      factors have a major influence on the properties of sludge. These influences are
      however still poorly understood, particularly with respect to the mechanisms
      involved and magnitude of such impacts. When taking note of the conspicuous
      biological characteristics of sludge, it becomes important that biological
      factors, such as the species composition and relative abundance of various
      microorganisms, as well as the microbial community characteristics that affect
      relevant operating processes, should be considered. 

PMID- 24462087
TI  - Plasmacatalytic removal of lead acetate assisted by precipitation.
AB  - The Gliding Arc Discharge (GAD) is an efficient non-thermal plasma technique able
      to degrade organic compounds dispersed in water at atmospheric pressure. The
      degradation of the organometallic lead acetate (PbAc) in aqueous solution was
      performed by two distinct plasmageneous processes: GAD and GAD/TiO2. The global
      oxidation of the organic matter was followed by Chemical Oxygen Demand (COD) and
      the mineralization was determined by the Total Organic Carbon (TOC). The Pb(2+)
      ions released during the degradation process were measured by Atomic Absorption
      Spectroscopy (AAS). For 2h of GAD treatment, the degradation rate of PbAc (10mM)
      reached 83% and for the same duration of GAD/TiO2 process ([TiO2]=1gL(-1)), it
      reached 93%. The release of Pb(2+) ions in the solution was respectively of 95%
      and 57% for GAD and GAD/TiO2 processes. The released Pb(2+) ions were removed by
      precipitation process in a basic medium at pH=11.1. A reaction mechanism was
      proposed to explain the PbAc molecule degradation and the Pb(2+) elimination. 

PMID- 24462088
TI  - Biological toxicity of groundwater in a seashore area: causal analysis and its
      spatial pollutant pattern.
AB  - To ensure the safety of groundwater usage in a seashore area where seawater
      incursion and unexpected leakage are taking place, this paper utilizes the
      Microtox test to quantify the biological toxicity of groundwater and proposes an
      integrated data analysis procedure based on hierarchical cluster analysis (HCA)
      and principal component analysis (PCA) for determining the key environmental
      factors that may result in the biological toxicity, together with the spatial
      risk pattern associated with groundwater usage. For these reasons, this study
      selects the coastal area of Taichung city in Central Taiwan as an example and
      implements a monitoring program with 40 samples. The results indicate that the
      concentration of total arsenic in the coastal areas is about 0.23-270.4 MUg L(
      1), which is obviously higher than the interior of Taichung city. Moreover, the
      seawater incursion and organic pollution in the study area may be the key factors
      resulting in the incubation of toxic substances. The results also indicate that
      As(3+) is the main contributor to biological toxicity compared to other
      disinfection by-products. With the help of the visualized spatial pollutants
      pattern of groundwater, an advanced water quality control plan can be made.

PMID- 24462089
TI  - The detrimental role of glial acidification during ischemia.
AB  - In this issue of Neuron, Beppu et al. (2014) demonstrate that glial acidification
      during ischemia contributes to neurotoxicity. Using a suite of in vivo
      optogenetic tools, the authors are able to exacerbate or attenuate neuronal
      damage during ischemia with glial acidification or alkalization, respectively.

PMID- 24462090
TI  - Programmed to be human?
AB  - Pletikos et al. (2014) demonstrate in this issue of Neuron that the human
      neocortex has an "hourglass" temporal gene expression pattern with robust and
      dynamic transcriptome differences during the prenatal and adolescent/adult
      periods. Similar changes are not observed in the nonhuman primate-is this what
      makes us human?

PMID- 24462091
TI  - CA3 sees the big picture while dentate gyrus splits hairs.
AB  - The dentate gyrus (DG) and area CA3 of the hippocampus have been long
      hypothesized to perform pattern separation and pattern completion, respectively.
      A new study published in this issue of Neuron, Neunuebel and Knierim (2014),
      provides strong empirical support for this functional dissociation. 

PMID- 24462092
TI  - Reactive gliosis and the multicellular response to CNS damage and disease.
AB  - The CNS is prone to heterogeneous insults of diverse etiologies that elicit
      multifaceted responses. Acute and focal injuries trigger wound repair with tissue
      replacement. Diffuse and chronic diseases provoke gradually escalating tissue
      changes. The responses to CNS insults involve complex interactions among cells of
      numerous lineages and functions, including CNS intrinsic neural cells, CNS
      intrinsic nonneural cells, and CNS extrinsic cells that enter from the
      circulation. The contributions of diverse nonneuronal cell types to outcome after
      acute injury, or to the progression of chronic disease, are of increasing
      interest as the push toward understanding and ameliorating CNS afflictions
      accelerates. In some cases, considerable information is available, in others,
      comparatively little, as examined and reviewed here. 

PMID- 24462093
TI  - CaMKII: claiming center stage in postsynaptic function and organization.
AB  - While CaMKII has long been known to be essential for synaptic plasticity and
      learning, recent work points to new dimensions of CaMKII function in the nervous
      system, revealing that CaMKII also plays an important role in synaptic
      organization. Ca(2+)-triggered autophosphorylation of CaMKII not only provides
      molecular memory by prolonging CaMKII activity during long-term plasticity (LTP)
      and learning but also represents a mechanism for autoactivation of CaMKII's
      multifaceted protein-docking functions. New details are also emerging about the
      distinct roles of CaMKIIalpha and CaMKIIbeta in synaptic homeostasis, further
      illustrating the multilayered and complex nature of CaMKII's involvement in
      synaptic regulation. Here, I review novel molecular and functional insight into
      how CaMKII supports synaptic function. 

PMID- 24462094
TI  - Orbitofrontal cortex as a cognitive map of task space.
AB  - Orbitofrontal cortex (OFC) has long been known to play an important role in
      decision making. However, the exact nature of that role has remained elusive.
      Here, we propose a unifying theory of OFC function. We hypothesize that OFC
      provides an abstraction of currently available information in the form of a
      labeling of the current task state, which is used for reinforcement learning (RL)
      elsewhere in the brain. This function is especially critical when task states
      include unobservable information, for instance, from working memory. We use this
      framework to explain classic findings in reversal learning, delayed alternation,
      extinction, and devaluation as well as more recent findings showing the effect of
      OFC lesions on the firing of dopaminergic neurons in ventral tegmental area (VTA)
      in rodents performing an RL task. In addition, we generate a number of testable
      experimental predictions that can distinguish our theory from other accounts of
      OFC function.

PMID- 24462095
TI  - Cell-type-specific labeling of synapses in vivo through synaptic tagging with
      recombination.
AB  - The study of synaptic specificity and plasticity in the CNS is limited by the
      inability to efficiently visualize synapses in identified neurons using light
      microscopy. Here, we describe synaptic tagging with recombination (STaR), a
      method for labeling endogenous presynaptic and postsynaptic proteins in a cell
      type-specific fashion. We modified genomic loci encoding synaptic proteins within
      bacterial artificial chromosomes such that these proteins, expressed at
      endogenous levels and with normal spatiotemporal patterns, were labeled in an
      inducible fashion in specific neurons through targeted expression of site
      specific recombinases. Within the Drosophila visual system, the number and
      distribution of synapses correlate with electron microscopy studies. Using two
      different recombination systems, presynaptic and postsynaptic specializations of
      synaptic pairs can be colabeled. STaR also allows synapses within the CNS to be
      studied in live animals noninvasively. In principle, STaR can be adapted to the
      mammalian nervous system.

PMID- 24462096
TI  - Optogenetic countering of glial acidosis suppresses glial glutamate release and
      ischemic brain damage.
AB  - The brain demands high-energy supply and obstruction of blood flow causes rapid
      deterioration of the healthiness of brain cells. Two major events occur upon
      ischemia: acidosis and liberation of excess glutamate, which leads to
      excitotoxicity. However, cellular source of glutamate and its release mechanism
      upon ischemia remained unknown. Here we show a causal relationship between glial
      acidosis and neuronal excitotoxicity. As the major cation that flows through
      channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic
      tool for instant intracellular acidification. Optical activation of ChR2
      expressed in glial cells led to glial acidification and to release of glutamate.
      On the other hand, glial alkalization via optogenetic activation of a proton
      pump, archaerhodopsin (ArchT), led to cessation of glutamate release and to the
      relief of ischemic brain damage in vivo. Our results suggest that controlling
      glial pH may be an effective therapeutic strategy for intervention of ischemic
      brain damage.

PMID- 24462097
TI  - Neuronal matrix metalloproteinase-9 is a determinant of selective
      neurodegeneration.
AB  - Selective neuronal loss is the hallmark of neurodegenerative diseases. In
      patients with amyotrophic lateral sclerosis (ALS), most motor neurons die but
      those innervating extraocular, pelvic sphincter, and slow limb muscles exhibit
      selective resistance. We identified 18 genes that show >10-fold differential
      expression between resistant and vulnerable motor neurons. One of these, matrix
      metalloproteinase-9 (MMP-9), is expressed only by fast motor neurons, which are
      selectively vulnerable. In ALS model mice expressing mutant superoxide dismutase
      (SOD1), reduction of MMP-9 function using gene ablation, viral gene therapy, or
      pharmacological inhibition significantly delayed muscle denervation. In the
      presence of mutant SOD1, MMP-9 expressed by fast motor neurons themselves
      enhances activation of ER stress and is sufficient to trigger axonal die-back.
      These findings define MMP-9 as a candidate therapeutic target for ALS. The
      molecular basis of neuronal diversity thus provides significant insights into
      mechanisms of selective vulnerability to neurodegeneration. 

PMID- 24462098
TI  - Age-dependent decrease in chaperone activity impairs MANF expression, leading to
      Purkinje cell degeneration in inducible SCA17 mice.
AB  - Although protein-misfolding-mediated neurodegenerative diseases have been linked
      to aging, how aging contributes to selective neurodegeneration remains unclear.
      We established spinocerebellar ataxia 17 (SCA17) knockin mice that inducibly
      express one copy of mutant TATA box binding protein (TBP) at different ages by
      tamoxifen-mediated Cre recombination. We find that more mutant TBP accumulates in
      older mouse and that this accumulation correlates with age-related decreases in
      Hsc70 and chaperone activity. Consistently, older SCA17 mice experienced earlier
      neurological symptom onset and more severe Purkinje cell degeneration. Mutant TBP
      shows decreased association with XBP1s, resulting in the reduced transcription of
      mesencephalic astrocyte-derived neurotrophic factor (MANF), which is enriched in
      Purkinje cells. Expression of Hsc70 improves the TBP-XBP1s interaction and MANF
      transcription, and overexpression of MANF ameliorates mutant TBP-mediated
      Purkinje cell degeneration via protein kinase C (PKC)-dependent signaling. These
      findings suggest that the age-related decline in chaperone activity affects
      polyglutamine protein function that is important for the viability of specific
      types of neurons. 

PMID- 24462099
TI  - Structural insights into competitive antagonism in NMDA receptors.
AB  - There has been a great level of enthusiasm to downregulate overactive N-methyl-D
      aspartate (NMDA) receptors to protect neurons from excitotoxicity. NMDA receptors
      play pivotal roles in basic brain development and functions as well as in
      neurological disorders and diseases. However, mechanistic understanding of
      antagonism in NMDA receptors is limited due to complete lack of antagonist-bound
      structures for the L-glutamate-binding GluN2 subunits. Here, we report the
      crystal structures of GluN1/GluN2A NMDA receptor ligand-binding domain (LBD)
      heterodimers in complex with GluN1- and GluN2-targeting antagonists. The crystal
      structures reveal that the antagonists, D-(-)-2-amino-5-phosphonopentanoic acid
      (D-AP5) and 1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA),
      have discrete binding modes and mechanisms for opening of the bilobed
      architecture of GluN2A LBD compared to the agonist-bound form. The current study
      shows distinct ways by which the conformations of NMDA receptor LBDs may be
      controlled and coupled to receptor inhibition and provides possible strategies to
      develop therapeutic compounds with higher subtype-specificity.

PMID- 24462100
TI  - Distinct Ca2+ sources in dendritic spines of hippocampal CA1 neurons couple to SK
      and Kv4 channels.
AB  - Small conductance Ca(2+)-activated K(+) (SK) channels and voltage-gated A-type
      Kv4 channels shape dendritic excitatory postsynaptic potentials (EPSPs) in
      hippocampal CA1 pyramidal neurons. Synaptically evoked Ca(2+) influx through N
      methyl-D-aspartate receptors (NMDARs) activates spine SK channels, reducing EPSPs
      and the associated spine head Ca(2+) transient. However, results using glutamate
      uncaging implicated Ca(2+) influx through SNX-482-sensitive (SNX-sensitive)
      Cav2.3 (R-type) Ca(2+) channels as the Ca(2+) source for SK channel activation.
      The present findings show that, using Schaffer collateral stimulation, the
      effects of SNX and apamin are not mutually exclusive and SNX increases EPSPs
      independent of SK channel activity. Dialysis with 1,2-bis(o-aminophenoxy)ethane
      N'N'N'-tetraacetic acid (BAPTA), application of 4-Aminopyridine (4-AP),
      expression of a Kv4.2 dominant negative subunit, and dialysis with a KChIPs
      antibody occluded the SNX-induced increase of EPSPs. The results suggest two
      distinct Ca(2+) signaling pathways within dendritic spines that link Ca(2+)
      influx through NMDARs to SK channels and Ca(2+) influx through R-type Ca(2+)
      channels to Kv4.2-containing channels. 

PMID- 24462101
TI  - Oscillatory dynamics and place field maps reflect hippocampal ensemble processing
      of sequence and place memory under NMDA receptor control.
AB  - Place coding in the hippocampus requires flexible combination of sensory inputs
      (e.g., environmental and self-motion information) with memory of past events. We
      show that mouse CA1 hippocampal spatial representations may either be anchored to
      external landmarks (place memory) or reflect memorized sequences of cell
      assemblies depending on the behavioral strategy spontaneously selected. These
      computational modalities correspond to different CA1 dynamical states, as
      expressed by theta and low- and high-frequency gamma oscillations, when switching
      from place to sequence memory-based processing. These changes are consistent with
      a shift from entorhinal to CA3 input dominance on CA1. In mice with a deletion of
      forebrain NMDA receptors, the ability of place cells to maintain a map based on
      sequence memory is selectively impaired and oscillatory dynamics are
      correspondingly altered, suggesting that oscillations contribute to selecting
      behaviorally appropriate computations in the hippocampus and that NMDA receptors
      are crucial for this function. 

PMID- 24462102
TI  - CA3 retrieves coherent representations from degraded input: direct evidence for
      CA3 pattern completion and dentate gyrus pattern separation.
AB  - Theories of associative memory suggest that successful memory storage and recall
      depend on a balance between two complementary processes: pattern separation (to
      minimize interference) and pattern completion (to retrieve a memory when
      presented with partial or degraded input cues). Putative attractor circuitry in
      the hippocampal CA3 region is thought to be the final arbiter between these two
      processes. Here we present direct, quantitative evidence that CA3 produces an
      output pattern closer to the originally stored representation than its degraded
      input patterns from the dentate gyrus (DG). We simultaneously recorded activity
      from CA3 and DG of behaving rats when local and global reference frames were
      placed in conflict. CA3 showed a coherent population response to the conflict
      (pattern completion), even though its DG inputs were severely disrupted (pattern
      separation). The results thus confirm the hallmark predictions of a longstanding
      computational model of hippocampal memory processing. 

PMID- 24462103
TI  - Long-range connectivity defines behavioral specificity of amygdala neurons.
AB  - Memories are acquired and encoded within large-scale neuronal networks spanning
      different brain areas. The anatomical and functional specificity of such long
      range interactions and their role in learning is poorly understood. The amygdala
      and the medial prefrontal cortex (mPFC) are interconnected brain structures
      involved in the extinction of conditioned fear. Here, we show that a defined
      subpopulation of basal amygdala (BA) projection neurons targeting the prelimbic
      (PL) subdivision of mPFC is active during states of high fear, whereas BA neurons
      targeting the infralimbic (IL) subdivision are recruited, and exhibit cell-type
      specific plasticity, during fear extinction. Pathway-specific optogenetic
      manipulations demonstrate that the activity balance between pathways is causally
      involved in fear extinction. Together, our findings demonstrate that, although
      intermingled locally, long-range connectivity defines distinct subpopulations of
      amygdala projection neurons and indicate that the formation of long-term
      extinction memories depends on the balance of activity between two defined
      amygdala-prefrontal pathways. 

PMID- 24462104
TI  - Neural dynamics of reaching following incorrect or absent motor preparation.
AB  - Moving is thought to take separate preparation and execution steps. During
      preparation, neural activity in primary motor and dorsal premotor cortices
      achieves a state specific to an upcoming action but movements are not performed
      until the execution phase. We investigated whether this preparatory state (more
      precisely, prepare-and-hold state) is required for movement execution using two
      complementary experiments. We compared monkeys' neural activity during delayed
      and nondelayed reaches and in a delayed reaching task in which the target
      switched locations on a small percentage of trials. Neural population activity
      bypassed the prepare-and-hold state both in the absence of a delay and if the
      wrong reach was prepared. However, the initial neural response to the target was
      similar across behavioral conditions. This suggests that the prepare-and-hold
      state can be bypassed if needed, but there is a short-latency preparatory step
      that is performed prior to movement even without a delay. 

PMID- 24462105
TI  - Scale-invariant movement encoding in the human motor system.
AB  - How does the human motor system encode our incredibly diverse motor repertoire in
      an efficient manner? One possible way of encoding movements efficiently is to
      represent them according to their shape/trajectory without regard to their size,
      by using neural populations that are invariant across scale. To examine this
      hypothesis, we recorded movement kinematics and functional magnetic resonance
      imaging (fMRI) while subjects wrote three letters in two different scales. A
      classification algorithm was trained to identify each letter according to its
      associated voxel-by-voxel response pattern in each of several motor areas.
      Accurate decoding of letter identity was possible in primary motor cortex (M1)
      and anterior intraparietal sulcus (aIPS) regardless of the letter's scale. These
      results reveal that large, distributed neural populations in human M1 and aIPS
      encode complex handwriting movements regardless of their particular dynamics and
      kinematics, in a scale-invariant manner.

PMID- 24462106
TI  - In vivo longitudinal Myelin Water Imaging in rat spinal cord following dorsal
      column transection injury.
AB  - Longitudinal Myelin Water Imaging was carried out in vivo to characterize white
      matter damage following dorsal column transection (DC Tx) injury at the lumbar
      level L1 of rat spinal cords. A transmit-receive implantable coil system was used
      to acquire multiple spin-echo (MSE) quantitative T2 data from the lumbar spinal
      cords of 16 rats at one week pre-injury as well as 3 and 8weeks post-injury (117
      microns in-plane resolution and 1.5mm slice thickness). In addition, ex vivo MSE
      and DTI data were acquired from cords fixed and excised at 3 or 8weeks post
      injury using a solenoid coil. The MSE data were used to generate Myelin Water
      Fractions (MWFs) as a surrogate measure of myelin content, while DTI data were
      acquired to study damage to the axons. Myelin damage was assessed histologically
      with Eriochrome cyanine (EC) and Myelin Basic Protein in degenerated myelin (dgen
      MBP) staining, and axonal damage was assessed by neurofilament-H in combination
      with neuron specific beta-III-tubulin (NF/Tub) staining. These MRI and
      histological measures of injury were studied in the dorsal column at 5mm cranial
      and 5mm caudal to injury epicenter. MWF increased significantly at 3weeks post
      injury at both the cranial and caudal sites, relative to baseline. The values on
      the cranial side of injury returned to baseline at 8weeks post-injury but
      remained elevated on the caudal side. This trend was found in both in vivo and ex
      vivo data. This MWF increase was likely due to the presence of myelin debris,
      which were cleared by 8 weeks on the cranial, but not the caudal, side. Both EC
      and dgen-MBP stains displayed similar trends. MWF showed significant correlation
      with EC staining (R=0.63, p=0.005 in vivo and R=0.74, p=0.0001 ex vivo). MWF also
      correlated strongly with the dgen-MBP stain, but only on the cranial side
      (R=0.64, p=0.05 in vivo; R=0.63, p=0.038 ex vivo). This study demonstrates that
      longitudinal MWI in vivo can accurately characterize white matter damage in DC Tx
      model of injury in the rat spinal cord. 

PMID- 24462107
TI  - Gender analysis of the anterior femoral condyle geometry of the knee.
AB  - BACKGROUND: No study has used 3-D anatomic knee models to investigate the gender
      differences in anterior femoral condyles. Therefore, this study aims to determine
      the morphologic differences between genders in anterior femoral condyles of the
      knees using 3-D anatomic knee models. METHODS: Ninety-six male and sixty-five
      female 3D anatomic knee models were used to measure lateral and medial anterior
      condyle heights, anterior trochlear groove heights, and anterior condyle width,
      which were normalized by the anterior-posterior and medial-lateral dimensions of
      the knee, respectively. The shape of anterior condyle groove was also analyzed.
      RESULTS: The mean lateral anterior condyle height, medial anterior condyle height
      and anterior condyle width of females were 6.6+/-1.8 mm, 2.0+/-2.3 mm, and 44.7+/
      4.2 mm, respectively. These data were significantly smaller (p<0.05) than those
      of males (7.7+/-1.8 mm, 2.9+/-2.0 mm and 50.0+/-3.4 mm). However, after
      normalizing by the femur size, the aspect ratios had no gender differences. Both
      the ranges of lateral and medial condyle of females were significantly smaller
      than those of males, and the geometry curve of anterior condyle was different
      between genders. CONCLUSION: Although the gender differences in anterior femoral
      condyle sizes no longer existed after normalization with the femur size, the
      shape and the peak position of anterior condyle groove still have gender
      differences. The data may have important implications on the current debate of
      gender-specific TKAs. CLINICAL RELEVANCE: This study provides a better
      understanding of gender differences in anterior femoral condyle geometry.

PMID- 24462108
TI  - Comparison the effect of lateral wedge insole and acupuncture in medial
      compartment knee osteoarthritis: a randomized controlled trial.
AB  - BACKGROUND: There is lack of well-designed trials evaluating structural benefits
      of non-pharmacologic therapies in knee osteoarthritis (OA). In this parallel
      group randomized controlled trial, we aim to compare the possible advantages of
      lateral wedge insole and acupuncture in patients with medial knee OA. METHOD:
      Patients with grade two or three of medial knee OA were randomly allocated to
      group one who received an in shoe lateral wedge and group two who underwent
      acupuncture. We assessed patients' pain, function and knee joint cartilage
      thickness before and after intervention. Paired t-test and independent samples t
      test were used for in group and between group analyses. ( LEVEL OF EVIDENCE: 2.)
      RESULTS: Twenty patients in each group were recruited in the study. Pain
      significantly decreased after therapy in both groups one and two (paired t test,
      P<0.001, 95% CI: 1.62-3.25 and 1.58-3.20 respectively). Function improved in each
      group (paired t test, P=0.001, 95% CI of 0.94-2.38 in group one and 0.97-2.43 in
      group two). A non-clinically statistically significant difference regarding the
      femoral and tibial cartilage thickness was obtained in both groups one (P=0.005,
      CI: -0.43-0.82 and P=0.037, CI: -0.44-0.80 respectively) and two (P=0.025, CI: 
      0.45-0.79 and P=0.035, CI: -0.29-0.96 respectively). Between groups analysis
      showed no significant difference regarding abovementioned measures. CONCLUSION:
      Both lateral wedge insole and acupuncture can be effective in the treatment of
      medial knee osteoarthritis without any superiority of one over the other. Iranian
      Registry of Clinical Trials: IRCT201201108235N1. URL:
      http://irct.ir/searchen.php.

PMID- 24462109
TI  - An innovative approach to tracheotomy in patients with major obstruction of the
      upper airway.
AB  - BACKGROUND: Patients with severe dyspnea consecutive to locally advanced
      obstructive head and neck squamous cell carcinoma (HNSCC) or subglottic stenosis
      requiring definitive or temporary tracheotomy are frequently difficult to
      ventilate and intubate. MATERIALS AND METHODS: We describe a new procedure to
      perform tracheotomy easily and safely in patients with major obstruction of the
      upper airway. A catheter, specifically designed for cricothyroidotomy, was
      inserted into the trachea under local anesthesia. Then, general anesthesia was
      induced and the catheter was used as a guide for dilatation tracheotomy. From
      November 2009 to March 2013, the procedure was successfully used in 13
      consecutive patients. Twelve out of 13 patients presented severe inspiratory
      dyspnea and stridor. RESULTS: During and after the procedure, no complications
      were reported. CONCLUSIONS: The reported technique is quickly performed and is a
      safe way to ensure short and long time ventilation of patients with major
      obstruction of the upper airway.

PMID- 24462110
TI  - Traumatic dislocation of intact mandibular condyle into middle cranial fossa.
AB  - INTRODUCTION: A 10-year-old girl presented to the Emergency Department with
      temporomandibular joint pain, malocclusion, and trismus after a bicycle accident.
      METHODS: CT of the temporal bones showed displacement of the right mandibular
      condyle into the middle cranial fossa with small intraparenchymal hemorrhage. The
      condyle was reduced using closed reduction technique and the patient was placed
      in maxillomandibular fixation. RESULTS: Complete reduction of the displaced
      condyle with resultant normal occlusion and persistent bony defect in the
      temporal bone. CONCLUSION: In early follow-up assessments the patient has had
      complete resolution of symptoms with residual bony defect from the site of
      fracture in the temporal bone.

PMID- 24462111
TI  - Airway management in an infant with a giant vallecular cyst.
AB  - Review vallecular cysts and report the surgical management of a vallecular cyst
      of unusual size with near-complete obliteration of the airway. This case report
      describes an unusually large mucus retention cyst in an 8-week-old infant that
      was diagnosed during induction of general anesthesia and prevented visualization
      of airway. Intubation was performed after rapid aspiration of the cyst contents.
      CONCLUSION: Vallecular cysts can present as a life-threatening obstruction in
      infants and complicate the establishment of an airway after induction of
      anesthesia. In our case, rapid thinking and aspiration of the cyst contents
      helped establish the airway for definitive CO2 laser excision.

PMID- 24462112
TI  - Nucleotide biosynthetic enzyme GMP synthase is a TRIM21-controlled relay of p53
      stabilization.
AB  - Nucleotide biosynthesis is fundamental to normal cell proliferation as well as to
      oncogenesis. Tumor suppressor p53, which prevents aberrant cell proliferation, is
      destabilized through ubiquitylation by MDM2. Ubiquitin-specific protease 7 (USP7)
      plays a dualistic role in p53 regulation and has been proposed to deubiquitylate
      either p53 or MDM2. Here, we show that guanosine 5'-monophosphate synthase (GMPS)
      is required for USP7-mediated stabilization of p53. Normally, most GMPS is
      sequestered in the cytoplasm, separated from nuclear USP7 and p53. In response to
      genotoxic stress or nucleotide deprivation, GMPS becomes nuclear and facilitates
      p53 stabilization by promoting its transfer from MDM2 to a GMPS-USP7
      deubiquitylation complex. Intriguingly, cytoplasmic sequestration of GMPS
      requires ubiquitylation by TRIM21, a ubiquitin ligase associated with autoimmune
      disease. These results implicate a classic nucleotide biosynthetic enzyme and a
      ubiquitin ligase, better known for its role in autoimmune disease, in p53
      control.

PMID- 24462113
TI  - Hexokinase-II positively regulates glucose starvation-induced autophagy through
      TORC1 inhibition.
AB  - Hexokinase-II (HK-II) catalyzes the first step of glycolysis and also functions
      as a protective molecule; however, its role in protective autophagy has not been
      determined. Results showed that inhibition of HK-II diminished, while
      overexpression of HK-II potentiated, autophagy induced by glucose deprivation in
      cardiomyocyte and noncardiomyocyte cells. Immunoprecipitation studies revealed
      that HK-II binds to and inhibits the autophagy suppressor, mTOR complex 1
      (TORC1), and that this binding was increased by glucose deprivation. The TOS
      motif, a scaffold sequence responsible for binding TORC1 substrates, is present
      in HK-II, and mutating it blocked its ability to bind to TORC1 and regulate
      protective autophagy. The transition from glycolysis to autophagy appears to be
      regulated by a decrease in glucose-6 phosphate. We suggest that HK-II binds TORC1
      as a decoy substrate and provides a previously unrecognized mechanism for
      switching cells from a metabolic economy, based on plentiful energy, to one of
      conservation, under starvation. 

PMID- 24462114
TI  - Phosphoproteomics screen reveals akt isoform-specific signals linking RNA
      processing to lung cancer.
AB  - The three Akt isoforms are functionally distinct. Here we show that their
      phosphoproteomes also differ, suggesting that their functional differences are
      due to differences in target specificity. One of the top cellular functions
      differentially regulated by Akt isoforms is RNA processing. IWS1, an RNA
      processing regulator, is phosphorylated by Akt3 and Akt1 at Ser720/Thr721. The
      latter is required for the recruitment of SETD2 to the RNA Pol II complex. SETD2
      trimethylates histone H3 at K36 during transcription, creating a docking site for
      MRG15 and PTB. H3K36me3-bound MRG15 and PTB regulate FGFR-2 splicing, which
      controls tumor growth and invasiveness downstream of IWS1 phosphorylation. Twenty
      one of the twenty-four non-small-cell-lung carcinomas we analyzed express IWS1.
      More importantly, the stoichiometry of IWS1 phosphorylation in these tumors
      correlates with the FGFR-2 splicing pattern and with Akt phosphorylation and Akt3
      expression. These data identify an Akt isoform-dependent regulatory mechanism for
      RNA processing and demonstrate its role in lung cancer. 

PMID- 24462116
TI  - Predictive factors for ankle syndesmosis injury in football players: a
      prospective study.
AB  - OBJECTIVES: Up to 25% of all ankle injuries involve the ankle syndesmosis and
      factors that increase risk have yet to be investigated prospectively. This study
      aimed to identify predictors of ankle syndesmosis injury in football players.
      DESIGN: A prospective study. METHODS: Rugby Union and Australian Football League
      players were recruited during 2010. Rugby League and different Rugby Union
      players were recruited during 2011. Baseline data collection included: age, body
      size, flexibility, strength and balance. Bivariate correlations were performed
      between all predictors. Variables with r >= 0.7 had only one variable entered in
      further analysis. Remaining predictor variables were analysed for association
      with the presence/absence of ankle syndesmosis injury. Variables with non
      significant association with injury (p>0.2) were included in a backward step-wise
      Cox regression model. RESULTS: 202 male participants aged 21 +/- 3.3 years (mean
      +/- SD) were recruited of whom 12 (5.9%) sustained an ankle syndesmosis injury.
      The overall incidence rate was 0.59/1000 h sport participation for Rugby Union
      and Rugby League. Australian Football League training data was not available. No
      significant predictors were identified; however, participants who sustained an
      injury during the season performed a higher vertical jump (63.6 +/- 8.2 cm) and
      greater Star Excursion Balance Test reach (80.5 +/- 5.3 cm), than participants
      who did not sustain an injury: 59.1 +/- 7.8 cm for Vertical Jump and 77.9 +/- 6.1
      cm for Star Excursion Balance Test. This was normalised for height. CONCLUSIONS:
      Variables such as age, body size, foot posture, flexibility and muscle strength
      did not increase risk of ankle syndesmosis injury. Jump height and balance
      performance may play a role in predicting ankle syndesmosis sprains.

PMID- 24462115
TI  - Nitric oxide sensing in plants is mediated by proteolytic control of group VII
      ERF transcription factors.
AB  - Nitric oxide (NO) is an important signaling compound in prokaryotes and
      eukaryotes. In plants, NO regulates critical developmental transitions and stress
      responses. Here, we identify a mechanism for NO sensing that coordinates
      responses throughout development based on targeted degradation of plant-specific
      transcriptional regulators, the group VII ethylene response factors (ERFs). We
      show that the N-end rule pathway of targeted proteolysis targets these proteins
      for destruction in the presence of NO, and we establish them as critical
      regulators of diverse NO-regulated processes, including seed germination,
      stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular
      mechanism for NO control of germination and crosstalk with abscisic acid (ABA)
      signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5).
      Our work demonstrates how NO sensing is integrated across multiple physiological
      processes by direct modulation of transcription factor stability and identifies
      group VII ERFs as central hubs for the perception of gaseous signals in plants.

PMID- 24462117
TI  - Psychometric properties of the modified RESIDE physical activity questionnaire
      among low-income overweight women.
AB  - OBJECTIVES: This study explored the criterion-related validity and test-retest
      reliability of the modified RESIDential Environment physical activity
      questionnaire and whether the instrument's validity varied by body mass index,
      education, race/ethnicity, or employment status. DESIGN: Validation study using
      baseline data collected for randomized trial of a weight loss intervention.
      METHODS: Participants recruited from health departments wore an ActiGraph
      accelerometer and self-reported non-occupational walking, moderate and vigorous
      physical activity on the modified RESIDential Environment questionnaire. We
      assessed validity (n=152) using Spearman correlation coefficients, and
      reliability (n=57) using intraclass correlation coefficients. RESULTS: When
      compared to steps, moderate physical activity, and bouts of moderate/vigorous
      physical activity measured by accelerometer, these questionnaire measures showed
      fair evidence for validity: recreational walking (Spearman correlation
      coefficients 0.23-0.36), total walking (Spearman correlation coefficients 0.24
      0.37), and total moderate physical activity (Spearman correlation coefficients
      0.18-0.36). Correlations for self-reported walking and moderate physical activity
      were higher among unemployed participants and women with lower body mass indices.
      Generally no other variability in the validity of the instrument was found.
      Evidence for reliability of RESIDential Environment measures of recreational
      walking, total walking, and total moderate physical activity was substantial
      (intraclass correlation coefficients 0.56-0.68). CONCLUSIONS: Evidence for
      questionnaire validity and reliability varied by activity domain and was
      strongest for walking measures. The questionnaire may capture physical activity
      less accurately among women with higher body mass indices and employed
      participants. Capturing occupational activity, specifically walking at work, may
      improve questionnaire validity.

PMID- 24462119
TI  - The Ernst triadic model: a good start?

PMID- 24462118
TI  - Safety and efficacy of sodium hyaluronate (IBD98E) in the induction of clinical
      and endoscopic remission in subjects with distal ulcerative colitis.
AB  - BACKGROUND: Sodium hyaluronate can contribute to the hydration and maintenance of
      the integrity of the intestinal mucosa. Restoration of the protective layer with
      sodium hyaluronate may contribute to the induction of remission of active
      ulcerative colitis. METHODS: We investigated the safety and efficacy of sodium
      hyaluronate enema (IBD98E) in distal active ulcerative colitis, in a prospective,
      uncontrolled, open-label pilot trial. Subjects with active distal ulcerative
      colitis (UCDAI >= 4 and sigmoidoscopy score >= 1) received IBD98E 60 mL enema
      once a day. Primary endpoints were safety and clinical response rate at Day 28.
      Secondary endpoints included clinical remission, endoscopic remission, and
      tolerability of IBD98E. Paired Student's t-test was performed to assess
      statistically significant differences in subjects between baseline and Day 28.
      RESULTS: Twenty-one subjects were enrolled. The overall safety profile was good;
      no serious adverse events were recorded. At Day 28, 9 subjects (42.9%) were
      clinical responders, and 10 subjects (47.6%) had an endoscopic response. Eight
      subjects (38.1%) achieved clinical remission, and 10 subjects (47.6%) achieved
      endoscopic remission. The mean average UCDAI score decreased from 6.10 to 3.81 at
      Day 28 (p=0.001), and average endoscopic score decreased from 1.57 to 1.10
      (p=0.004). CONCLUSION: IBD98E seems to be safe and effective for the induction of
      clinical and endoscopic remission. Placebo-controlled studies are warranted.

PMID- 24462120
TI  - The role of disease management programs in the health behavior of chronically ill
      patients.
AB  - OBJECTIVE: Investigate the effects of disease management program (DMP)
      implementation on physical activity, smoking, and physical quality of life among
      chronically ill patients. METHODS: This study used a mixed-methods approach
      involving qualitative (35 interviews with project managers) and quantitative
      (survey of patients from 18 DMPs) data collection. Questionnaire response rates
      were 51% (2010; 2619/5108) at T0 and 47% (2011; 2191/4693) at T1. RESULTS:
      Physical activity and the percentage of smokers improved significantly over time,
      whereas physical quality of life declined. After adjusting for patients' physical
      quality of life at T0, age, educational level, marital status, and gender,
      physical activity at T0 (p<0.01), changes in physical activity (p<0.001), and
      percentage of smokers at T0 (p<0.05) predicted physical quality of life at T1.
      Project managers reported that DMPs improved patient-professional interaction.
      The ability to set more concrete targets improved patients' health behaviors.
      CONCLUSIONS: DMPs appear to improve physical activity among chronically ill
      patients over time. Furthermore, (changes in) health behavior are important for
      the physical quality of life of chronically ill patients. PRACTICE IMPLICATIONS:
      Redesigning care systems and implementing DMPs based on the chronic care model
      may improve health behavior among chronically ill patients.

PMID- 24462121
TI  - Nitric oxide therapy for post-laparoscopic surgery associated patent foramen
      ovale: incidence, mechanisms, diagnosis and therapy.
AB  - OBJECTIVE: Postoperative hypoxemia is a common clinical challenge. The diagnosis
      of an underlying cause of hypoxemia may not immediately be apparent. Clinically
      silent and non-functional intracardiac shunt may become apparent and pose
      significant management problems in the postoperative period. DATA SOURCE: We
      describe a case where clinically significant hypoxemia resulted from a patent
      foramen ovale (PFO) after laparoscopic surgery due to changes in the intra
      abdominal and intrathoracic pressures. CONCLUSION: This condition was effectively
      diagnosed by bedside echocardiography, and was effectively treated with nitric
      oxide.

PMID- 24462122
TI  - N-type calcium channel antibody-mediated paraneoplastic limbic encephalitis: a
      diagnostic challenge.
AB  - BACKGROUND: The etiology of encephalitis presents a diagnostic challenge and
      often remains a mystery. However, current technological advances using antibodies
      can enable a definitive diagnosis in cases that would previously have been
      suspected to be idiopathic or viral encephalitis. Our objective is to show that
      tonsil neuroendocrine carcinoma can present initially as limbic encephalitis
      mediated by N-type calcium channel antibodies and to highlight the diagnostic
      confusion before cancer detection. METHODS: We report a rare case of
      neuroendocrine cancer presenting as limbic encephalopathy, Lambert-Eaton
      myasthenic syndrome and neuropathy. The patient was diagnosed and treated at The
      University of Texas MD Anderson Cancer Center in November 2011. RESULTS:
      Paraneoplastic limbic encephalitis was diagnosed based on clinical presentation
      of seizures, short-term memory loss, retrograde amnesia, disorientation,
      distractibility, and abulia; on the exclusion of brain metastases, CNS infection,
      stroke, metabolic or nutritional deficits, or medication-related events; and on
      CSF results with inflammatory findings and an abnormal electroencephalography
      study that showed seizure activity in the left temporal lobe. Serum
      paraneoplastic panel was positive for P/Q-type calcium channel antibody and N
      type calcium channel antibody. Magnetic resonance imaging of brain was
      unremarkable. CONCLUSION: This case highlights limbic encephalitis as an atypical
      presentation of neuroendocrine cancer. It also illustrates how treatment of the
      underlying cancer can reverse limbic encephalitis and Lambert-Eaton myasthenic
      syndrome in a neuroendocrine carcinoma patient even before the paraneoplastic
      panel becomes negative.

PMID- 24462123
TI  - Comparison of dopamine transporter decline in a patient with Parkinson's disease
      and normal aging effect.
AB  - We report serial dopamine transporter (DAT) positron emission tomography (PET)
      scanning in a patient with Parkinson's disease (PD). Six months after motor
      symptom onset, the patient was diagnosed with PD, Hoehn-Yahr stage 1 at age 71,
      and underwent DAT PET scanning at ages 71, 72, 74, and 75. Volumes-of-interest
      were placed on the ventral striatum (vST), pre-commissural dorsal caudate
      (preDCA), post-commissural caudate (postCA), pre-commissural dorsal putamen
      (preDPU), and post-commissural putamen (postPU); the results were compared to the
      age-related regression line created by using the data of 16 healthy subjects. For
      the patient, DAT availability in the vST, preDCA, postCA, preDPU, and postPU at
      the first scanning was 5.5%, 26.2%, 29.9%, 34.5%, and 60.2% lower, respectively,
      compared to the age-related regression line. The rates of DAT decline in the vST,
      preDCA, postCA, preDPU, and postPU were 5.3%, 5.4%, 8.5%, 6.2%, and 7.8% per
      year, respectively. The postPU is well known to be an initial region of DAT
      decline and be severely affected throughout the illness. If the decline follows
      an exponential pattern, in this case, DAT decline in the postPU is speculated to
      start about 10 years before the motor symptom onset.

PMID- 24462124
TI  - The anterolateral fasciocutaneous thigh flap for circumferential pharyngeal
      defects--can it really replace the jejunum?
AB  - Free jejunal transfer has been used in pharyngeal reconstruction for many years,
      but many have criticised it as being unreliable, poorly tolerant of radiotherapy,
      and susceptible to stenosis and dysphagia. Recently, the trend has been to use
      the anterolateral thigh (ALT) flap to overcome these problems, and many authors
      have reported good results. At the University of Birmingham we used the jejunal
      free flap for pharyngeal reconstruction for many years, but in view of recent
      reports we changed to the ALT flap. We retrospectively analysed all patients who
      had pharyngeal reconstruction with an ALT flap in our unit since changing from
      the jejunal flap. Only circumferential defects were included. Six patients had
      pharyngeal resection and required reconstruction of a circumferential defect
      between 2007 and 2010. All the defects were reconstructed with a tubed ALT flap.
      No flaps failed and there was no partial necrosis. However, stricturing still
      occurred and the diet of many patients was restricted. Three patients required
      the flap to be replaced with a jejunal free flap. Although no flaps failed, we
      have not been able to replicate the results of other surgeons and have therefore
      abandoned use of the ALT flap and returned to use of the jejunal free flap for
      the reconstruction of circumferential pharyngeal defects. 

PMID- 24462125
TI  - Accuracy of maxillary repositioning in two-jaw surgery with conventional
      articulator model surgery versus virtual model surgery.
AB  - The purpose of this study was to compare the accuracy of maxillary repositioning
      using the recently introduced computerized virtual model surgery (VMS) with
      conventional articulator model surgery (AMS). Forty-two patients who had
      undergone bimaxillary surgery were investigated retrospectively in this study.
      The patients were divided into two groups: conventional AMS (n = 23) and VMS (n =
      19) for intermediate splint fabrication in maxillary positioning. Planned
      surgical movements and actual postsurgical changes of the lateral and frontal
      cephalometric measurements were compared. Although variations from the planned
      surgical movements were relatively small, both methods had statistically
      significant errors in some of the linear measurements. Both groups had a similar
      range of errors. The overall absolute mean discrepancy between the planned and
      actual surgical movements for the linear measurements was 1.17 mm (0-3.6 mm) in
      AMS and 0.95 mm (0-3.2 mm) in VMS. Of the total measurements, measurements
      reflecting a surgical discrepancy of more than 2 mm or 2 degrees  comprised 12.0%
      of the cases in AMS and 7.9% in VMS. The surgical accuracy of maxillary
      positioning with VMS was comparable to conventional AMS. Because VMS has the
      definitive advantage of eliminating the complex laboratory step and shortening
      the laboratory time, this can be accepted as an alternative to AMS.

PMID- 24462126
TI  - TNFRII polymorphism is associated with response to TNF blockers in rheumatoid
      arthritis patients seronegative for ACPA.

PMID- 24462127
TI  - Difficulties in the diagnosis of vertebral fracture in men: agreement between
      doctors.
AB  - The agreement for vertebral fracture (VF) diagnosis in men, between doctors is
      poor. OBJECTIVES: To assess the agreement for VF diagnosis, in men, on standard
      radiographs, between experts, before and after consensual workshop and
      establishing an algorithm. METHODS: The agreement between thirteen experimented
      rheumatologists has been calculated in thirty osteoporotic men. Then, the group
      discussed in a workshop and 28 other radiograph sets of osteoporotic men with
      follow-up radiographs and incident confirmed VF, have been reviewed. The experts
      identified and hierarchised 18 pathological features of vertebral deformation and
      established an algorithm of VF diagnosis. Eleven experts have realized a second
      reading of the first set of radiographs. We compared the agreement between the 2
      readings without and with the algorithm. RESULTS: After consensus and the use of
      the algorithm the results are: number of fractured patients (with at least 1 VF)
      according to the experts varies from 13 to 26 patients out of 30 (13 to 28 during
      the first reading). The agreement between the experts at the patient level is 75%
      (70% at the first reading). Among the 390 vertebrae analyzed by the experts, the
      number of VF detected varies from 18 to 59 (18 to 98 at the first reading). The
      agreement between the experts at the vertebral level is 92% (89% at the first
      reading). The algorithm allows a good improvement of the agreement, especially
      for 8 of the 11 experts. Discrepancies for the VF diagnosis between experts
      exist. The algorithm improves the agreement.

PMID- 24462128
TI  - MRI, CT scan, and dynamic radiographs for coccydynia: comment on the article
      "role for magnetic resonance imaging in coccydynia with sacrococcygeal
      dislocation", by Trouvin et al., Joint Bone Spine 2013;80:214-16.

PMID- 24462129
TI  - Current diagnosis and treatment of polymyalgia rheumatica.
AB  - The diagnostic and therapeutic strategies for polymyalgia rheumatica (PMR) have
      changed substantially in recent years. Rather than a single disease entity, PMR
      has emerged as a syndrome produced by a variety of conditions. The diagnostic
      criteria that have been used for several decades are inadequate. These facts
      support a new and broader pathological concept, polymyalgic syndrome, and a
      standardized diagnostic and therapeutic approach designed to rule out diseases
      with misleading presentations and to identify the limited number of patients with
      polymyalgic syndrome who have PMR. Criteria for both polymyalgic syndrome and PMR
      were developed recently but remain to be validated. These criteria are discussed,
      as well as the suggested diagnostic approach and treatment strategy. In contrast,
      studies on pathophysiological models, inflammatory mechanisms, and genetic
      factors are not considered herein, as they were conducted in heterogeneous
      populations of patients who did not meet the new criteria. Current data indicate
      that polymyalgic syndrome is a mode of onset of inflammatory joint disease in
      individuals older than 50 years of age and not (in most cases) a disease entity.

PMID- 24462130
TI  - Canakinumab in a case of adult onset still's disease: efficacy only on systemic
      manifestations.

PMID- 24462131
TI  - Gout in French Polynesia: a survey of common practices.

PMID- 24462132
TI  - The effect of non-fluoride factors on risk of dental fluorosis: evidence from
      rural populations of the Main Ethiopian Rift.
AB  - Elevated level of fluoride (F(-)) in drinking water is a well-recognized risk
      factor of dental fluorosis (DF). While considering optimization of region
      specific standards for F(-), it is reasonable, however, to consider how local
      diet, water sourcing practices, and non-F(-) elements in water may be related to
      health outcomes. In this study, we hypothesized that non-F(-) elements in
      groundwater and lifestyle and demographic characteristics may be independent
      predictors or modifiers of the effects of F(-) on teeth. Dental examinations were
      conducted among 1094 inhabitants from 399 randomly-selected households of 20
      rural communities of the Ziway-Shala lake basin of the Main Ethiopian Rift. DF
      severity was evaluated using the Thylstrup-Fejerskov Index (TFI). Household
      surveys were performed and water samples were collected from community water
      sources. To consider interrelations between the teeth within individual (in terms
      of DF severity) and between F(-) and non-F(-) elements in groundwater, the
      statistical methods of regression analysis, mixed models, and principal component
      analysis were used. About 90% of study participants consumed water from wells
      with F(-) levels above the WHO recommended standard of 1.5mg/l. More than 62% of
      the study population had DF. F(-) levels were a major factor associated with DF.
      Age, sex, and milk consumption (both cow's and breastfed) were also statistically
      significantly (p<0.05) associated with DF severity; these associations appear
      both independently and as modifiers of those identified between F(-)
      concentration and DF severity. Among 35 examined elements in groundwater, Ca, Al,
      Cu, and Rb were found to be significantly correlated with dental health outcomes
      among the residents exposed to water with excessive F(-) concentrations.
      Quantitative estimates obtained in our study can be used to explore new water
      treatment strategies, water safety and quality regulations, and lifestyle
      recommendations which may be more appropriate for this highly populated region. 

PMID- 24462133
TI  - Simultaneous determination of thirteen organophosphate esters in settled indoor
      house dust and a comparison between two sampling techniques.
AB  - An analytical method for the simultaneous determination of 13 organophosphate
      esters (OPEs) in house dust was developed. The method is based on solvent
      extraction by sonication, sample cleanup by solid phase extraction (SPE), and
      analysis by gas chromatography-positive chemical ionization-tandem mass
      spectrometry (GC/PCI-MS/MS). Method detection limits (MDLs) ranged from 0.03 to
      0.43 MUg/g and recoveries from 60% to 118%. The inter- and intra-day variations
      ranged from 3% to 23%. The method was applied to dust samples collected using two
      vacuum sampling techniques from 134 urban Canadian homes: a sample of fresh or
      "active" dust (FD) collected by technicians and a composite sample taken from the
      household vacuum cleaner (HD). Results show that the two sampling methods (i.e.,
      FD vs HD) provided comparable results. Tributoxyethyl phosphate (TBEP), triphenyl
      phosphate (TPhP), tris(chloropropyl) phosphate (TCPP), tri(2-chloroethyl)
      phosphate (TCEP), tris(dichloro-isopropyl) phosphate (TDCPP), tricresyl phosphate
      (TCrP), and tri-n-butyl phosphate (TnBP) were detected in the majority of
      samples. The most predominant OPE was TBEP, with median concentrations of 31.9
      MUg/g and 22.8 MUg/g in FD and HD samples, respectively, 1 to 2 orders of
      magnitude higher than other OPEs. The method was also applied to the analysis of
      OPEs in the National Institute of Standards and Technology (NIST) standard
      reference material (NIST SRM 2585, organic contaminants in house dust). The
      results from SRM 2585 may contribute to the certification of OPE concentration
      values in this SRM.

PMID- 24462134
TI  - Monitoring the developmental impact of copper and silver nanoparticle exposure in
      Drosophila and their microbiomes.
AB  - There is concern that waste waters containing manufactured metal nanoparticles
      (NPs) originating from consumer goods, will find their way into streams and
      larger water bodies. Aquatic invertebrates could be vulnerable to such pollution,
      and here we have used fruit flies, Drosophila melanogaster, as a model
      invertebrate, to test for the effect of NPs on fitness. Both copper NP and
      microparticle (MP)-containing medium slowed development, reduced adult longevity
      and decreased sperm competition. In contrast, ingestion of silver resulted in a
      significant reduction in developmental success only if the metal particles were
      nanosized. Ag NP-treatments resulted in reduced developmental success as assessed
      by larval and pupal survival as well as larval climbing ability, but there was no
      impact of silver on adult longevity and little effect on reproductive success.
      However, Cu NPs generally appeared to be no more toxic to this invertebrate model
      than the bulk counterpart. The impact of silver ingestion in larvae was further
      investigated by 454 pyrosequencing of the 16S rRNA genes of the midgut flora.
      There was a striking reduction in the diversity of the gut microbiota of Ag NP
      treated larvae with a rise in the predominance of Lactobacillus brevis and a
      decrease in Acetobacter compared to control or Ag MP-treatment groups.
      Importantly, these experiments show that perturbation of the microbial assemblage
      within a metazoan model may contribute to Ag NP-mediated toxicity. These
      observations have implications for impact assessments of nanoparticles as
      emerging contaminants. 

PMID- 24462135
TI  - Hemodynamic decompensation caused by acute myocardial infarction in an adult with
      Ebstein's anomaly.

PMID- 24462136
TI  - Coronary flow dynamics in children after repair of Tetralogy of Fallot.
AB  - OBJECTIVES: To assess the possible effect of a stiff right ventricle on the
      coronary flow (CF) in patients with post-operative Tetralogy of Fallot (TOF).
      BACKGROUND: Right ventricular restrictive physiology i.e. forward flow during
      atrial contraction (RVRP), is characteristic to many patients with post-operative
      TOF. METHODS: A total of 34 patients with TOF anatomically corrected through
      transatrial repair were included. Coronary flow parameters were registered with
      transthoracic Doppler echocardiography from posterior descending (PDCA) and left
      anterior descending (LAD) coronary arteries in the same patient in 24/34 (71%)
      patients. Twenty age-matched healthy children were used as controls. Cardiac
      magnetic resonance (CMR) imaging was used to detect myocardial fibrosis, RV
      volume, and RVRP. RESULTS: The mean age at investigation was 10.2 +/- 2.8 years.
      RV end diastolic and end systolic volumes indexed for BSA were larger in patients
      with RVRP (p=0.002 and 0.008 respectively). Peak flow velocity in diastole and
      flow velocity time integral was increased in patients compared to controls. They
      were increased in the LAD in patients with fibrosis of RV (n=11) compared to
      patients without fibrosis (n=9) (p=0.01 and 0.047 respectively). LAD coronary
      flow was especially increased in patients with RVRP (n=9) as compared with those
      without (n=11), (p=0.006). CONCLUSIONS: Patients at mid-term followup after
      correction of TOF show increase of coronary flow. This increase is more
      pronounced in patients with fibrosis and RVRP of the RV.

PMID- 24462137
TI  - Revascularization improves mortality in elderly patients with acute myocardial
      infarction complicated by cardiogenic shock.

PMID- 24462138
TI  - Association of interleukin 8 with myocardial infarction: results from the
      Stockholm Heart Epidemiology Program.
AB  - BACKGROUND: Interleukin 8 (IL8) has been contradictorily associated with the risk
      of myocardial infarction (MI). AIM: To investigate the association of IL8 serum
      levels with the risk of MI and the association of the IL8 (IL8) and IL8 receptors
      (CXCR1 and CXCR2) genetic variants with IL8 levels and MI risk in a large case
      control study, the Stockholm Heart Epidemiology Program. METHODS AND RESULTS: IL8
      levels (pg/mL) were divided into quartiles and the MI risk was calculated by
      logistic regression and expressed as odds ratio (OR) and 95% CI. Two IL8 SNPs
      (rs4073A/T, rs2227306C/T) and three SNPs tagging CXCR1 and CXCR2 (rs4674258C/T,
      rs1008563C/T, rs6723449T/C) were analyzed for association with IL8 levels and
      with MI risk. Multivariate adjusted ORs for MI risk by IL8 levels in the highest
      quartiles indicated reduced point estimates in both women (OR 0.37; 95% CI 0.2
      0.8) and men when compared to the lowest quartile. In female cases, IL8 levels
      decreased progressively in the six months after MI (p=0.03). IL8, CXCR1 and CXCR2
      genetic variants were not associated with IL8 levels. In men, the T allele at the
      IL8 SNP rs4073 was associated with a slight increase in the MI risk under an
      additive and a recessive model of inheritance. CONCLUSIONS: IL8 serum levels were
      associated with a reduced occurrence of MI among women, whereas IL8 was
      associated with a slightly increased risk among men, possibly through different
      mechanisms. These data suggest that the biological effects of IL8 on MI risk may
      vary over time and warrant further cohort studies with repetitive IL8
      measurements.

PMID- 24462139
TI  - Clinical outcomes with 6 months dual antiplatelet therapy after implantation of
      biolimus-A9 drug eluting coronary stents.
AB  - INTRODUCTION: Duration of dual antiplatelet therapy (DAPT) following drug eluting
      stent (DES) implantation remains poorly defined. Endothelialisation of
      biodegradable polymer biolimus-eluting stents occurs early, and 6 months DAPT may
      be adequate. AIMS: We evaluated long term outcome in patients treated with
      biolimus-eluting stents who were treated with 6 months DAPT. Endpoints included
      cardiac death and non-fatal stent thrombosis occurring 6 to 12 months after stent
      implantation. METHODS: 692 patients (77.2% male), aged 65.6 +/- 12.5 years
      received biolimus-eluting DES (March 2008 -November 2011). Vital status was
      tracked through the Medical Research Information Service. Episodes of non-fatal
      stent thrombosis, (Academic Research Consortium definition) between months 6 and
      12 were tracked via systematic database searches (5 PCI centres). RESULTS:
      Presentations included acute coronary syndrome (47.2%) and stable coronary
      disease (52.8%). Vessels treated included left main stem (6.8%), left anterior
      descending (37.4%), circumflex (19.1%), right coronary artery (34.5%) and
      saphenous vein graft (2.1%) respectively. High-risk subsets included diabetes
      (15.6%); AHA type C lesions (35.1%) and chronic total occlusions (12.8%). During
      median follow-up of 700 days (0 to 1392) there were 42 deaths (6.1%); 4.2% at 0-6
      months, 1.0% at 6-12 months and 0.9% at >12 months. Of the 7 deaths between 6 and
      12 months, one death was adjudicated as possible stent thrombosis. There were no
      cases of non-fatal known stent thrombosis. All cause mortality accrued with
      smooth decremental incidence. Statistical examination showed no evidence of event
      clustering between 6 and 12 months. CONCLUSIONS: After implantation of
      biodegradable polymer biolimus-eluting coronary stents, 6 months DAPT appears to
      be adequate, safe and effective.

PMID- 24462140
TI  - Prevalence and prognostic implications of different types of atrial fibrillation
      in patients admitted to a coronary care unit.

PMID- 24462141
TI  - Assessment of guideline adherence in hospitalised heart failure patients with
      systolic dysfunction in Dubai, United Arab Emirates.

PMID- 24462142
TI  - Increased risk of ischemic heart disease in young patients with migraine: a
      population-based, propensity score-matched, longitudinal follow-up study.
AB  - BACKGROUND: The association between migraine and the risk of ischemic heart
      disease (IHD) remains controversial. The purpose of the present population-based,
      propensity score-matched follow-up study was to investigate whether young
      migraineurs are at a higher risk of developing IHD. METHODS: A total of 11,541
      subjects aged between 18 and 45 years with at least two ambulatory visits with
      the principal diagnosis of migraine in 2001 were enrolled in the migraine group.
      We used a logistic regression model that included age, sex, pre-existing
      comorbidities, and socioeconomic status as covariates to compute the propensity
      score. The non-migraine group consisted of 11,541 propensity score-matched,
      randomly sampled subjects without migraine. The 3-year IHD-free survival rate and
      the cumulative incidence of IHD were estimated using the Kaplan-Meier method.
      Stratified Cox proportional hazard regression with patients matched by propensity
      score was used to estimate the effect of migraine on the risk of developing
      subsequent IHD. RESULTS: The mean age in both groups was 32.3 years. During
      follow-up, 121 subjects in the migraine group and 55 in the non-migraine group
      developed IHD. The incidence rate of IHD was 4.56 (95% confidence interval [CI],
      3.78 to 5.44) per 1000 person-years in the migraine group and 2.00 (95% CI, 1.51
      to 2.61) per 1000 person-years in the non-migraine group. Compared to the non
      migraine group, the HR of IHD for the migraine group was 2.50 (95% CI, 1.78 to
      3.52, P<0.0001). CONCLUSIONS: This study showed an increased risk of developing
      IHD in young patients with newly diagnosed migraine.

PMID- 24462143
TI  - Not all pathogenic mutations are pathogenic: KCNH2 mutations in two sisters with
      tetralogy of Fallot.

PMID- 24462144
TI  - Post-procedural renal microvascular perfusion measured using the Quantitative
      Blush Evaluator (QuBE) predicts improvement in renal function in patients
      undergoing percutaneous renal artery stenting.

PMID- 24462145
TI  - Successful management of a twice complicated case by implantation of three
      CoreValve prostheses.

PMID- 24462146
TI  - Catheter-based renal sympathetic denervation is effective in reducing office and
      ambulatory blood pressure in patients with resistant hypertension.

PMID- 24462147
TI  - Effect of sinus rhythm restoration on platelet function in patients with lone
      atrial fibrillation.

PMID- 24462148
TI  - Preperitoneal fat tissue may be associated with arterial stiffness in obese
      adolescents.
AB  - Vascular aging is a chronic process, and many negative effects of obesity in this
      process have been well defined. We assessed arterial stiffness in obese
      adolescents and evaluated the relationship between intra-abdominal fat
      distribution and arterial stiffness. Arterial stiffness parameters and pulse wave
      velocity (PWV) were evaluated in 61 obese adolescents and 58 healthy controls.
      Carotid-femoral PWV was calculated by arterial tonometry. Additionally, all obese
      children were evaluated for metabolic syndrome and insulin resistance. Intra
      abdominal fat distribution, including subcutaneous, preperitoneal and visceral
      fat thicknesses, was assessed by ultrasonography. PWVs of obese children were
      significantly higher than those of healthy controls (5.0 +/- 0.7 m/s vs. 4.7 +/-
      0.5 m/s). Parameters affecting PWV were evaluated by regression analysis. The
      independent variable in the regression analysis model was PWV, and the dependent
      variables were age, metabolic syndrome, body mass index and Homeostasis Model
      Assessment--Insulin Resistance, as well as subcutaneous, preperitoneal and
      visceral fat tissue thicknesses measured by ultrasonography. The only parameter
      associated with PWV was preperitoneal fat tissue thickness. Vascular changes
      related to obesity may begin in adolescence, as illustrated by the increased PWV.
      Preperitoneal fat tissue may be related to arterial stiffness. Intra-abdominal
      fat distributions obtained by ultrasonography may provide clinicians with
      valuable information needed to determine cardiovascular disease risk factors in
      obese adolescents.

PMID- 24462149
TI  - In vivo lateral blood flow velocity measurement using speckle size estimation.
AB  - In previous studies, we proposed blood measurement using speckle size estimation,
      which estimates the lateral component of blood flow within a single image frame
      based on the observation that the speckle pattern corresponding to blood
      reflectors (typically red blood cells) stretches (i.e., is "smeared") if blood
      flow is in the same direction as the electronically controlled transducer line
      selection in a 2-D image. In this observational study, the clinical viability of
      ultrasound blood flow velocity measurement using speckle size estimation was
      investigated and compared with that of conventional spectral Doppler of carotid
      artery blood flow data collected from human patients in vivo. Ten patients (six
      male, four female) were recruited. Right carotid artery blood flow data were
      collected in an interleaved fashion (alternating Doppler and B-mode A-lines) with
      an Antares Ultrasound Imaging System and transferred to a PC via the Axius
      Ultrasound Research Interface. The scanning velocity was 77 cm/s, and a 4-s
      interval of flow data were collected from each subject to cover three to five
      complete cardiac cycles. Conventional spectral Doppler data were collected
      simultaneously to compare with estimates made by speckle size estimation. The
      results indicate that the peak systolic velocities measured with the two methods
      are comparable (within +/-10%) if the scan velocity is greater than or equal to
      the flow velocity. When scan velocity is slower than peak systolic velocity, the
      speckle stretch method asymptotes to the scan velocity. Thus, the speckle stretch
      method is able to accurately measure pure lateral flow, which conventional
      Doppler cannot do. In addition, an initial comparison of the speckle size
      estimation and color Doppler methods with respect to computational complexity and
      data acquisition time indicated potential time savings in blood flow velocity
      estimation using speckle size estimation. Further studies are needed for
      calculation of the speckle stretch method across a field of view and combination
      with an appropriate axial flow estimator.

PMID- 24462150
TI  - Use of real-time ultrasonography as an alternative method for early detection,
      confirmation and evaluation of rat pregnancy.
AB  - Researchers sometimes face difficulties in the diagnosis of pregnancy and
      assessment of embryonic development. Ultrasonography (US) is a non-invasive
      imaging method with minimal side effects on the subjects or operators. It
      provides real-time evaluation of the physiology of rapidly moving structures
      (i.e., heart) and facilitates evaluation of fetal tissue development. US discerns
      tissues based on composition, making it the imaging method of choice for
      abdominal examination. In this study we used real-time US as an alternative
      method for early diagnosis of pregnancy in rats. Sixty-four Wistar rats aged 16
      20 wk were examined, and day 8 was the earliest point at which pregnancy could be
      detected. We constructed a detailed timeline of embryonic features detectable by
      US on days 8 to 19. We trust this index will be a valuable tool. More refined
      work toward a more detailed "atlas" will help to reduce animal sacrifice during
      embryonic development studies.

PMID- 24462151
TI  - Modeling of errors in Nakagami imaging: illustration on breast mass
      characterization.
AB  - Nakagami imaging is an attractive tissue characterization method, as the
      parameter estimated at each location is related to properties of the tissues. The
      application to clinical ultrasound images is problematic, as the estimation of
      the parameters is disturbed by the presence of complex structures. We propose to
      consider separately the different aspects potentially affecting the value of the
      Nakagami parameters and quantify their effects on the estimation. This framework
      is applied to the classification of breast masses. Quantitative parameters are
      computed on two groups of ultrasound images of benign and malignant tumors. A
      statistical analysis of the result indicated that the previously observed
      difference between average values of the Nakagami parameters is explained mostly
      by estimation errors. In the future, new methods for reliable computation of
      Nakagami parameters need to be developed, and factors of error should be
      considered in studies using Nakagami parameters. 

PMID- 24462153
TI  - Stellate masses and histologic grades in breast cancer.
AB  - Breast masses with a radiologic stellate pattern often transform into
      malignancies, but their tendency to be of low histologic grade yields a better
      survival rate compared with tumors with other patterns on mammography screening.
      This study was designed to investigate the correlation of histologic grade with
      stellate features extracted from the coronal plane of 3-D ultrasound images. A
      pre-processing method was proposed to facilitate the extraction of stellate
      features. Extracted features were statistically measured to derive a set of
      indices that quantitatively represent the stellate pattern. These indices then
      went through a selection procedure to build proper decision trees. The splitting
      rules of decision trees indicated that stellate tumors are associated with low
      grade. A set of indices from the low grade-associated rules has the potential to
      represent the stellate feature. Further investigation of the hypoechoic region of
      peripheral tissue is essential to establishment of a complete discriminating
      model for tumor grades.

PMID- 24462152
TI  - Application of high-intensity focused ultrasound to the study of mild traumatic
      brain injury.
AB  - Though intrinsically of much higher frequency than open-field blast
      overpressures, high-intensity focused ultrasound (HIFU) pulse trains can be
      frequency modulated to produce a radiation pressure having a similar form. In
      this study, 1.5-MHz HIFU pulse trains of 1-ms duration were applied to intact
      skulls of mice in vivo and resulted in blood-brain barrier disruption and immune
      responses (astrocyte reactivity and microglial activation). Analyses of variance
      indicated that 24 h after HIFU exposure, staining density for glial fibrillary
      acidic protein was elevated in the parietal and temporal regions of the cerebral
      cortex, corpus callosum and hippocampus, and staining density for the microglial
      marker, ionized calcium binding adaptor molecule, was elevated 2 and 24 h after
      exposure in the corpus callosum and hippocampus (all statistical test results, p
      < 0.05). HIFU shows promise for the study of some bio-effect aspects of blast
      related, non-impact mild traumatic brain injuries in animals.

PMID- 24462154
TI  - Can contrast-enhanced ultrasound distinguish malignant from reactive lymph nodes
      in patients with head and neck cancers?
AB  - The purpose of this study was to investigate the utility of contrast-enhanced
      ultrasound in differentiating benign from malignant cervical lymph nodes in
      patients with squamous cell carcinoma of the head and neck. A consecutive series
      of 17 patients with known head and neck malignancy scheduled for neck surgery and
      lymph node clearance were recruited for contrast-enhanced ultrasound evaluation.
      Sonographic signal intensity as a function of time, comparing features of time to
      peak, time to arrival and time to wash-out, was quantified. The selected node was
      removed surgically and submitted for histology. Contrast-enhanced ultrasound
      examination had 100% sensitivity and 85.7% specificity for lymph node
      involvement. Functional analysis revealed contrast peaks significantly earlier in
      the malignant nodes (mean +/- standard deviation) of 24.14 +/- 2.7 s compared
      with 29.33 +/- 3.4 s (p = 0.0128). Contrast-enhanced ultrasound holds promise in
      the detection and characterization of metastatic nodes that would not be
      diagnosed as abnormal on the basis of conventional ultrasound criteria.

PMID- 24462156
TI  - Involvement of mitochondrial and reactive oxygen species in the sonodynamic
      toxicity of chlorin e6 in human leukemia K562 cells.
AB  - It is well accepted that sonodynamic therapy (SDT) exerts cytotoxicity and anti
      tumor activity in many human tumors through the induction of cell apoptosis. The
      aim of the work described here was to study the effect of chlorin e6 (Ce6)
      mediated SDT on human chronic myelogenous leukemia K562 cells. Our results
      indicate that Ce6-mediated SDT can suppress the viability of K562 cells. SDT
      caused apoptosis as analyzed by annexin V-phycoerythrin/7-amino-actinomycin D
      staining as well as cleavage of caspase 3 and the polypeptide poly(ADP-ribose)
      polymerase. After SDT exposure, loss of mitochondrial membrane potential,
      translocation of Bax from cytoplasm to mitochondria and activation of caspase 9
      indicated that the mitochondrial-related apoptotic pathway might be activated.
      This process was accompanied by rapid generation of reactive oxygen species
      (ROS). Scavenging of ROS significantly blocked caspase-3 expression and the
      killing effect of SDT on K562 cells. Stress-activated protein kinases c-jun NH2
      terminal kinase (JNK) and the p38 mitogen-activated protein kinase were activated
      after SDT treatment. Together, these findings indicate that Ce6-mediated SDT
      triggers mitochondria- and caspase-dependent apoptosis; oxidative injury may play
      a vital role in apoptotic signaling cascades. 

PMID- 24462155
TI  - Sonoporation-induced depolarization of plasma membrane potential: analysis of
      heterogeneous impact.
AB  - Disrupting plasma membrane integrity would inevitably promote anomalous ion
      fluxes across the membrane and thereby upset the trans-membranous potential. In
      this article, we report new findings on how sonoporation as a physical membrane
      perforation strategy would lead to different forms of plasma membrane potential
      disruption. Our investigation was conducted with a customized fluorescence
      imaging platform that enabled live monitoring of plasma membrane potential in
      relation to individual sonoporation events triggered on HeLa cervical cancer
      cells. Sonovue microbubbles were used as sonoporation agents (added at a 4:3 cell
      to-bubble ratio), and they were activated by 1-MHz pulsed ultrasound with 0.35
      MPa peak negative pressure, 20-cycle pulse duration, 20-Hz pulse repetition
      frequency and 1-s total exposure duration. Results indicate that the plasma
      membrane potential response was heterogeneous among sonoporated cells: (i)
      membrane potential of irreversibly sonoporated cells was permanently depolarized;
      (ii) reversibly sonoporated cells exhibited either transient or sustained
      membrane depolarization; (iii) intact cells adjacent to sonoporated ones
      underwent transitory membrane depolarization. These findings effectively serve to
      substantiate the causal relationship between sonoporation and plasma membrane
      potential. 

PMID- 24462157
TI  - Detection of hepatic hemodynamics in normal rhesus monkeys using high-frequency
      ultrasound.
AB  - The rhesus monkey liver disease model provides useful information for hepatic
      research, as studies of hepatic hemodynamics in humans are rare. A 3-9 MHz high
      frequency linear transducer (iU22, Philips Medical Systems, Royal Philips
      Electronics, The Netherlands) was used to obtain ultrasonograms of the livers of
      28 normal rhesus monkeys (16 males, 12 females). Diameters of the portal vein and
      proper hepatic artery; maximum velocity of the portal vein; and peak-systolic and
      end-diastolic velocity and resistive index of the proper hepatic artery were also
      assessed. The portal vein and proper hepatic artery were 0.584 +/- 0.123 and
      0.151 +/- 0.052 cm in diameter, respectively. The maximum velocity of the portal
      vein was 40.2 +/- 13.7 cm/s. Peak systolic velocity and resistive index of the
      proper hepatic artery were 72.2 +/- 25.4 cm/s and 0.67 +/- 0.10, respectively. We
      found that high-frequency Doppler ultrasonography can be used to obtain clear
      portal vein and proper hepatic artery ultrasonograms and to measure the
      hemodynamic parameters of the portal vein and proper hepatic artery in rhesus
      monkeys. It is thus an effective method for studying changes in hepatic
      hemodynamics and has interesting technical and therapeutic implications. Our
      results provide useful information and establish normal reference values for
      future studies of adult healthy rhesus monkeys.

PMID- 24462158
TI  - Heterogeneous echogenicity of the thyroid parenchyma does not influence the
      detection of multi-focality in papillary thyroid carcinoma on preoperative
      ultrasound staging.
AB  - Heterogeneous echogenicity and micro-nodulations of diffuse thyroid disease on
      ultrasonography (US) might influence the diagnostic performance of pre-operative
      US staging, especially the detection of multi-focality. This study was designed
      to determine whether heterogeneous echogenicity of the thyroid parenchyma
      influences the diagnostic performance of US in the detection of multi-focality in
      papillary thyroid carcinoma. Between December 2010 and April 2011, 811 patients
      underwent pre-operative staging US for papillary thyroid carcinoma and surgery.
      Twelve radiologists performed the pre-operative US for T and N staging.
      Underlying parenchymal echogenicity and unilateral and bilateral multi-focality
      of the thyroid nodules were also evaluated. Patients were divided into two groups
      on the basis of the underlying echogenicity of the thyroid gland. To evaluate the
      diagnostic accuracy of US with respect to underlying echogenicity, the
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy were calculated and compared between the two groups. Among the 811
      patients included, US revealed underlying heterogeneous echogenicity of the
      thyroid parenchyma in 204 (25.2%) and underlying homogeneous echogenicity of the
      thyroid parenchyma in 607 (74.8%). There were no significant differences between
      the two groups in the diagnostic performance of pre-operative staging US in
      predicting unilateral multi-focality and bilaterality. Underlying heterogeneous
      echogenicity in a thyroid gland with Hashimoto's thyroiditis does not
      significantly influence the detection of multi-focality in papillary thyroid
      cancer on pre-operative US staging. 

PMID- 24462159
TI  - Relative blood flow changes measured using calibrated frequency-weighted Doppler
      power at different hematocrit levels.
AB  - In theory, the power of a trans-cranial Doppler signal may be used to measure
      changes in blood flow and vessel diameter in addition to velocity. In this study,
      a flow index (FI) of relative changes in blood flow was derived from frequency
      weighted Doppler power signals. The FI, plotted against velocity, was calibrated
      to the zero intercept with absent flow to reduce the effects of non-uniform
      vessel insonation. An area index was also calculated. FIs were compared with
      actual flow in four silicone tubes of different diameter at increasing flow rates
      and increasing hematocrit (Hct) in a closed-loop phantom model. FI values were
      strongly correlated with actual flow, at constant Hct, but varied substantially
      with changes in Hct. Percentage changes in area indexes, relative to the 4-mm
      tube, were strongly correlated with tube cross-sectional area. The implications
      of these results for in vivo use are discussed.

PMID- 24462160
TI  - Magnetic resonance imaging for the exploitation of bubble-enhanced heating by
      high-intensity focused ultrasound: a feasibility study in ex vivo liver.
AB  - Bubble-enhanced heating (BEH) may be exploited to improve the heating efficiency
      of high-intensity focused ultrasound in liver and to protect tissues located
      beyond the focal point. The objectives of this study, performed in ex vivo pig
      liver, were (i) to develop a method to determine the acoustic power threshold for
      induction of BEH from displacement images measured by magnetic resonance acoustic
      radiation force imaging (MR-ARFI), and (ii) to compare temperature distribution
      with MR thermometry for HIFU protocols with and without BEH. The acoustic
      threshold for generation of BEH was determined in ex vivo pig liver from MR-ARFI
      calibration curves of local tissue displacement resulting from sonication at
      different powers. Temperature distributions (MR thermometry) resulting from
      "conventional" sonications (20 W, 30 s) were compared with those from "composite"
      sonications performed at identical parameters, but after a HIFU burst pulse (0.5
      s, acoustic power over the threshold for induction of BEH). Displacement images
      (MR-ARFI) were acquired between sonications to measure potential modifications of
      local tissue displacement associated with modifications of tissue acoustic
      characteristics induced by the burst HIFU pulse. The acoustic threshold for
      induction of BEH corresponded to a displacement amplitude of approximately 50 MUm
      in ex vivo liver. The displacement and temperature images of the composite group
      exhibited a nearly spherical pattern, shifted approximately 4 mm toward the
      transducer, in contrast to elliptical shapes centered on the natural focal
      position for the conventional group. The gains in maximum temperature and
      displacement values were 1.5 and 2, and the full widths at half-maximum of the
      displacement data were 1.7 and 2.2 times larger than in the conventional group in
      directions perpendicular to ultrasound propagation axes. Combination of MR-ARFI
      and MR thermometry for calibration and exploitation of BEH appears to increase
      the efficiency and safety of HIFU treatment.

PMID- 24462161
TI  - High-intensity focused ultrasound treatment of late-stage pancreatic body
      carcinoma: optimal tumor depth for safe ablation.
AB  - Objective criteria are currently not available for assessing the extent of
      ablation by high-intensity focused ultrasound (HIFU). A retrospective review was
      conducted in Chinese patients with late-stage pancreatic body carcinoma treated
      with 1 h/d intermittent HIFU at a single center. Clinical and procedure-related
      characteristics were examined in relation to tumor posterior depth. Clinically,
      tumor ablation was negatively correlated with posterior tumor depth, with a 1-cm
      increase in depth decreasing ablation by 30.7%. At a computed tomography (CT)
      determined 7-cm posterior tumor depth (considered the critical value for the
      procedure), ablation sensitivity and specificity were 77.8% and 72.7%,
      respectively. Tumor ablation >30% in patients with a CT-determined posterior
      tumor depth <=7 cm was 9.333 times better than that in patients with a CT
      determined posterior tumor depth >7 cm. Adverse effects did not affect the
      efficacy of HIFU. Tumors with posterior depths <7 cm may effectively be treated
      with HIFU-induced ablation with minimal adverse events.

PMID- 24462162
TI  - On the acoustic properties of vaporized submicron perfluorocarbon droplets.
AB  - The acoustic characteristics of microbubbles created from vaporized submicron
      perfluorocarbon droplets with fluorosurfactant coating are examined. Utilizing
      ultra-high-speed optical imaging, the acoustic response of individual
      microbubbles to low-intensity diagnostic ultrasound was observed on clinically
      relevant time scales of hundreds of milliseconds after vaporization. It was found
      that the vaporized droplets oscillate non-linearly and exhibit a resonant bubble
      size shift and increased damping relative to uncoated gas bubbles due to the
      presence of coating material. Unlike the commercially available lipid-coated
      ultrasound contrast agents, which may exhibit compression-only behavior,
      vaporized droplets may exhibit expansion-dominated oscillations. It was further
      observed that the non-linearity of the acoustic response of the bubbles was
      comparable to that of SonoVue microbubbles. These results suggest that vaporized
      submicron perfluorocarbon droplets possess the acoustic characteristics necessary
      for their potential use as ultrasound contrast agents in clinical practice. 

PMID- 24462163
TI  - Phase grouping-based needle segmentation in 3-D trans-rectal ultrasound-guided
      prostate trans-perineal therapy.
AB  - A robust and efficient needle segmentation method used to localize and track the
      needle in 3-D trans-rectal ultrasound (TRUS)-guided prostate therapy is proposed.
      The algorithmic procedure begins by cropping the 3-D US image containing a
      needle; then all voxels in the cropped 3-D image are grouped into different line
      support regions (LSRs) based on the outer product of the adjacent voxels'
      gradient vector. Two different needle axis extraction methods in the candidate
      LSR are presented: least-squares fitting and 3-D randomized Hough transform.
      Subsequent local optimization refines the position of the needle axis. Finally,
      the needle endpoint is localized by finding an intensity drop along the needle
      axis. The proposed methods were validated with 3-D TRUS tissue-mimicking agar
      phantom images, chicken breast phantom images and patient images obtained during
      prostate cryotherapy. The results of the in vivo test indicate that our method
      can localize the needle accurately and robustly with a needle endpoint
      localization accuracy <1.43 mm and detection accuracy >84%, which are favorable
      for 3-D TRUS-guided prostate trans-perineal therapy.

PMID- 24462164
TI  - Hydrogen peroxide ingestion: a rare case of portal venous gas.

PMID- 24462165
TI  - Peroral endoscopic myotomy: a 4-step approach to a challenging procedure.

PMID- 24462166
TI  - Scanning fiber endoscopy: a novel platform for cholangioscopy.

PMID- 24462167
TI  - Acute pancreatitis caused by Anisakis.

PMID- 24462168
TI  - Endoscopically identified well-differentiated rectal carcinoid tumors: impact of
      tumor size on the natural history and outcomes.
AB  - BACKGROUND: There is a paucity of data pertaining to the natural history and
      outcomes of patients with well-differentiated rectal carcinoids. OBJECTIVE: To
      correlate endoscopic size with the natural history and outcome. DESIGN:
      Retrospective study. SETTING: Single tertiary referral center. PATIENTS: Eighty
      seven patients with endoscopically identified well-differentiated rectal
      carcinoid tumors. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS:
      Prevalence of metastasis at diagnosis, disease progression, and survival.
      RESULTS: Metastasis was present at diagnosis in 3%, 66%, and 73% of tumors
      measuring <=10 mm, 11 to 19 mm, and >=20 mm, respectively. Metastasis was
      predicted with 100% sensitivity and 87% specificity using an endoscopic lesion
      size >=9 mm. In patients without identified metastasis, 64% were identified
      during screening colonoscopy. Within this select cohort, subsequent metastasis
      was discovered only at distant extra pelvic sites, in 1.6%, 50%, and 100% of
      patients with tumors initially measuring <=10 mm, 11 to 19 mm, and >=20 mm,
      respectively. The carcinoid related 5- and 10-year survival rates for locally
      confined disease were 96%. The corresponding survival rates for local and
      advanced metastatic disease were 60% and 35%, respectively. LIMITATIONS:
      Subjective estimation of tumor size, mitotic index or Ki-67 labeling index not
      reported, and lack of formal and standardized baseline staging algorithm and
      surveillance program. CONCLUSIONS: The clinical behavior of 11- to 19-mm tumors
      appears to mimic that of larger (>20 mm) lesions with respect to the presence of
      metastasis at diagnosis and disease progression. Therefore, if local therapy is
      contemplated, we propose to make a distinction between <=10-mm and 11- to 19-mm
      tumors, favoring an aggressive staging and management protocol for 11- to 19-mm
      carcinoid tumors.

PMID- 24462169
TI  - Endoscopic resection of an ampullary gangliocytic paranganglioma.

PMID- 24462170
TI  - Systematic review comparing radiofrequency ablation and complete endoscopic
      resection in treating dysplastic Barrett's esophagus: a critical assessment of
      histologic outcomes and adverse events.
AB  - BACKGROUND: With recent advances in endoscopy, endoscopic techniques have
      surpassed esophagectomy in the treatment of dysplastic Barrett's esophagus (BE).
      OBJECTIVE: To compare the efficacy and safety of complete EMR and radiofrequency
      ablation (RFA) in the treatment of dysplastic BE. DESIGN: Systematic review of
      literature. PATIENTS: Diagnosis of BE with high-grade dysplasia or intramucosal
      cancer. INTERVENTION: Complete EMR or RFA. MAIN OUTCOME MEASUREMENTS: Complete
      eradication of dysplasia and intestinal metaplasia at the end of treatment and
      after >12 months' follow-up. Adverse event rates associated with treatment.
      RESULTS: A total of 22 studies met the inclusion criteria. Only 1 trial directly
      compared the 2 techniques; most studies were observational case series. Dysplasia
      was effectively eradicated at the end of treatment in 95% of patients after
      complete EMR and 92% after RFA. After a median follow-up of 23 months for
      complete EMR and 21 months for RFA, eradication of dysplasia was maintained in
      95% of patients treated with complete EMR and 94% treated with RFA. Short-term
      adverse events were seen in 12% of patients treated with complete EMR but in only
      2.5% of those treated with RFA. Esophageal strictures were adverse events in 38%
      of patients treated with complete EMR, compared with 4% of those treated with
      RFA. Progression to cancer appeared to be rare after treatment, although follow
      up was short. LIMITATIONS: Small studies, heterogeneous in design, with variable
      outcome measures. Also follow-up durations were short, limiting evaluation of
      long-term durability of both treatments. CONCLUSION: RFA and complete EMR are
      equally effective in the short-term treatment of dysplastic BE, but adverse event
      rates are higher with complete EMR.

PMID- 24462171
TI  - Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery
      marking: a pilot clinical study.
AB  - BACKGROUND: Biopsy surveillance protocols for the assessment of Barrett's
      esophagus can be subject to sampling errors, resulting in diagnostic uncertainty.
      Optical coherence tomography is a cross-sectional imaging technique that can be
      used to conduct volumetric laser endomicroscopy (VLE) of the entire distal
      esophagus. We have developed a biopsy guidance platform that places
      endoscopically visible marks at VLE-determined biopsy sites. OBJECTIVE: The
      objective of this study was to demonstrate in human participants the safety and
      feasibility of VLE-guided biopsy in vivo. DESIGN: A pilot feasibility study.
      SETTING: Massachusetts General Hospital. PATIENTS: A total of 22 participants
      were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's
      esophagus. Twelve participants were used to optimize the laser marking parameters
      and the system platform. A total of 30 target sites were selected and marked in
      real-time by using the VLE-guided biopsy platform in the remaining 10
      participants. INTERVENTION: Volumetric laser endomicroscopy. MAIN OUTCOME
      MEASUREMENTS: Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the
      tissue between the laser cautery marks. RESULTS: There were no adverse events of
      VLE and laser marking. The optimal laser marking parameters were determined to be
      2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these
      parameters were visible on endoscopy and VLE. The accuracies for diagnosing
      tissue in between the laser cautery marks by independent blinded readers for
      endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to
      biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images
      100% when compared with histopathology interpretations. LIMITATIONS: This is a
      single-center feasibility study with a limited number of patients. CONCLUSION:
      Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can
      be used to guide biopsy site selection based on the acquired volumetric optical
      coherence tomography imaging data. ( CLINICAL TRIAL REGISTRATION NUMBER:
      NCT01439633.).

PMID- 24462172
TI  - Single institutional experience using biological mesh for abdominal wall
      reconstruction.
AB  - BACKGROUND: Complex ventral hernias remain a challenge. We present a study
      evaluating outcomes of complex ventral hernia repair using human-derived
      acellular dermal matrix (AlloDerm) and porcine-derived acellular dermal sheet
      (Permacol). METHODS: A retrospective review of 251 patients undergoing complex
      hernia repair was performed. Primary outcome was hernia recurrence; and secondary
      outcomes included early and late complications and mortality. RESULTS: Recurrence
      for Permacol versus AlloDerm was 32% versus 47% (P = .02). There was a difference
      in early complications (48% vs 30%, P = .007) and also late complications (30% vs
      21%, P = .16) of Permacol versus AlloDerm. Overall survival was 85% for the
      Permacol group versus 78% for the AlloDerm group (P = .23). Recurrence for
      Permacol versus AlloDerm for underlay technique was 19% versus 22% and that for
      bridging technique was 44% versus 57%. CONCLUSION: There exists a high
      complication rate from both Permacol and AlloDerm in complex ventral hernia
      repair especially when used as a fascial bridge.

PMID- 24462173
TI  - Liver transplantation for acute liver failure related to autochthonous genotype 3
      hepatitis E virus infection.
AB  - Hepatitis E virus of genotype 3 (HEV-3) is an emerging cause of sporadic
      autochthonous acute hepatitis in Europe. Although spontaneous outcome of
      hepatitis E is usually favorable, fulminant liver failure has been described
      worldwide. In Europe, autochthonous hepatitis E associated with fulminant hepatic
      failure and leading to liver transplantation has been exceptionally reported. We
      report here four cases of fulminant and sub-fulminant hepatitis E proposed for
      liver transplantation in Marseille University hospitals between July 2006 and
      March 2010. HEV diagnosis relied on detection of anti-HEV IgM antibodies and HEV
      RNA in serum samples. All cases were men, with no travel history in hyperendemic
      areas. HEV sequence analyses revealed genotype 3 HEV in the four patients. Liver
      histology indicated severe acute hepatitis in all of them, pre-existing fibrosis
      being found in two cases. Two patients underwent liver transplantation, and the
      two other patients could not be transplanted due to septic complications and
      died. HEV testing should be performed for the initial evaluation of every acute
      liver failure regardless of the epidemiological and clinical context. With
      respect to the potentially fulminant evolution of HEV genotype 3 infections,
      treatment with ribavirin of severe acute hepatitis E should be considered. 

PMID- 24462174
TI  - A previously unidentified risk of needlestick injury in the emergency medical
      services setting.

PMID- 24462175
TI  - Cleaning of filtering facepiece respirators contaminated with mucin and
      Staphylococcus aureus.
AB  - BACKGROUND: Decontamination, cleaning, and reuse of filtering facepiece
      respirators (FFRs) has been proposed to mitigate an acute FFR shortage during a
      public health emergency. Our study evaluates the ability of commercially
      available wipe products to clean FFRs contaminated with either infectious or
      noninfectious aerosols. METHODS: Three models of surgical N95 FFRs were
      contaminated with aerosols of mucin or viable Staphylococcus aureus then cleaned
      with hypochlorite, benzalkonium chloride, or nonantimicrobial wipes. After
      cleaning, FFRs were separated into components (nose pad, fabrics, and perforated
      strip), and contaminants were extracted and quantified. Filtration performance
      was assessed for cleaned FFRs. RESULTS: Mucin removal was <1 log for all wipe
      products on all components. Inert wipes achieved ~1-log attenuation in viable S
      aureus on fabrics from all FFR models--removal was less effective from nose pads
      and perforated edges. Both antimicrobial wipes achieved 3-5-log attenuation on
      most components, with smaller reductions on nose pads and greater reductions on
      perforated strips. Particle penetration following cleaning yielded mean values
      <5%. The highest penetrations were observed in FFRs cleaned with benzalkonium
      chloride wipes. CONCLUSIONS: FFRs can be disinfected using antimicrobial wipe
      products, but not effectively cleaned with the wipes evaluated in this study.
      This study provides informative data for the development of better FFRs and
      applicable cleaning products.

PMID- 24462176
TI  - Identification of dihydrostilbenes in Pholidota chinensis as a new scaffold for
      GABAA receptor modulators.
AB  - A dichloromethane extract of stems and roots of Pholidota chinensis (Orchidaceae)
      enhanced GABA-induced chloride currents (I(GABA)) by 132.75 +/- 36.69% when
      tested at 100 MUg/mL in a two-microelectrode voltage clamp assay, on Xenopus
      laevis oocytes expressing recombinant alpha1beta2gamma2S GABA(A) receptors. By
      means of an HPLC-based activity profiling approach, the three structurally
      related stilbenoids coelonin (1), batatasin III (2), and pholidotol D (3) were
      identified in the active fractions of the extract. Dihydrostilbene 2 enhanced
      I(GABA) by 1512.19 +/- 176.47% at 300 MUM, with an EC50 of 52.51 +/- 16.96 MUM,
      while compounds 1 and 3 showed much lower activity. The relevance of
      conformational flexibility for receptor modulation by stilbenoids was confirmed
      with a series of 13 commercially available stilbenes and their corresponding
      semisynthetic dihydro derivatives. Dihydrostilbenes showed higher activity in the
      oocyte assay than their corresponding stilbenes. The dihydro derivatives of
      tetramethoxy-piceatannol (12) and pterostilbene (20) were the most active among
      these derivatives, but they showed lower efficiencies than compound 2. Batatasin
      III (2) showed high efficiency but no significant subunit specificity when tested
      on the receptor subtypes alpha1beta2gamma2s, alpha2beta2gamma2s,
      alpha3beta2gamma2s, alpha4beta2gamma2s, alpha5beta2gamma2s, alpha1beta1gamma2s,
      and alpha1beta3gamma2s. Dihydrostilbenes represent a new scaffold for GABA(A)
      receptor modulators.

PMID- 24462177
TI  - Synthesis and properties of double-stranded RNA-bindable oligodiaminogalactose
      derivatives conjugated with vitamin E.
AB  - RNA interference (RNAi) is a gene-regulating system that is controlled by
      external short interfering RNAs (siRNAs). Sequence selective gene silencing by
      siRNA shows promise in clinical research. However, there have been few efficient
      methods for delivering siRNAs to target cells. In this study, we propose a novel
      type of RNA duplex-bindable molecule with an oligodiaminosaccharide structure.
      These 2,6-diamino-2,6-dideoxy-(1-4)-beta-D-galactopyranose oligomers
      (oligodiaminogalactoses; ODAGals) conjugated with alpha-tocopherol (vitamin E;
      VE) or a VE analog were designed as novel siRNA-bindable molecules that can be
      utilized to deliver RNAi drugs to the liver. Among these compounds, the VE analog
      bound ODAGal was suggested to bind to RNA duplexes without inhibiting RNAi
      activity.

PMID- 24462179
TI  - Contaminants of legacy and emerging concern in largescale suckers (Catostomus
      macrocheilus) and the foodweb in the lower Columbia River, Oregon and Washington,
      USA.
AB  - We investigated occurrence, transport pathways, and effects of polybrominated
      diphenyl ether (PBDE) flame retardants and other endocrine disrupting chemicals
      (EDCs) in aquatic media and the foodweb in the lower Columbia River. In 2009 and
      2010, foodweb sampling at three sites along a gradient of contaminant exposure
      near Skamania (Washington), Columbia City (Oregon) and Longview (Washington)
      included water (via passive samplers), bed sediment, invertebrate biomass
      residing in sediment, a resident fish species (largescale suckers [Catostomus
      macrocheilus]), and eggs from osprey (Pandion haliaetus). This paper primarily
      reports fish tissue concentrations. In 2009, composites of fish brain, fillet,
      liver, stomach, and gonad tissues revealed that overall contaminant
      concentrations were highest in livers, followed by brain, stomach, gonad, and
      fillet. Concentrations of halogenated compounds in tissue samples from all three
      sites ranged from <1 to 400nanograms per gram of wet tissue. Several chemical
      classes, including PBDEs, organochlorine pesticides, and polychlorinated
      biphenyls (PCBs), were detected at all sites and in nearly all fish tissues
      sampled. In 2010, only fish livers were sampled and inter-site concentration
      differences were not as pronounced as in 2009. Chemical concentrations in
      sediments, fish tissues, and osprey eggs increased moving downstream from
      Skamania to the urbanized sites near Columbia City and Longview. Numerous
      organochlorine (OC) pesticides, both banned and currently used, and PBDEs, were
      present at each site in multiple media and concentrations exceeded environmental
      quality benchmarks in some cases. Frequently detected OC compounds included
      hexachlorobenzene, pentachloroanisole, dichlorodiphenyltrichloroethane (DDT) and
      its degradates, chlorpyrifos, and oxyfluorofen. Biomagnification of BDE47, 100,
      153, and 154 occurred in largescale suckers and osprey eggs. Results support the
      hypothesis that contaminants in the environment lead to bioaccumulation and
      potential negative effects in multiple levels of the foodweb. 

PMID- 24462178
TI  - Risk factors for hospital-acquired pneumonia caused by carbapenem-resistant Gram
      negative bacteria in critically ill patients: a multicenter study in Korea.
AB  - We performed a case-control study to identify risk factors of carbapenem
      resistant Gram-negative bacteria (CRGNB) as an increasing cause of hospital
      acquired pneumonia (HAP). The study included critically ill adult patients with
      HAP whose microbial etiology was identified at eight tertiary centers in Korea
      between June 2008 and December 2009. Eighty two patients with 86 isolates of
      CRGNB (62 Acinetobacter baumannii, 14 Pseudomonas aeruginosa, and 10
      Stenotrophomonas maltophilia) were included in the case group, and 122 patients
      with carbapenem-susceptible Gram-negative bacteria were included in the control
      group. Diabetes mellitus (adjusted odds ratio [aOR] 2.82, 95% confidence interval
      [95% CI] 1.25-6.38), radiologic score >=5 (aOR 4.56, 95% CI 2.36-8.81), prior
      fluoroquinolone (aOR 2.39. 95% CI = 1.07-5.35), or carbapenem usage (aOR 2.82,
      95% CI 1.75-17.83) were found to be independent risk factors. Fluoroquinolone and
      carbapenem should be cautiously used to avoid HAP caused by CRGNB. 

PMID- 24462180
TI  - Lactation driven dynamics of adiponectin supply from different fat depots to
      circulation in cows.
AB  - Adipose tissue (AT) depots are heterogeneous in terms of morphology and adipocyte
      metabolism. Adiponectin, one of the most abundant adipokines, is known for its
      insulin sensitizing effects and its role in glucose and lipid metabolism. Little
      is known about the presence of adiponectin protein in visceral (vc) and
      subcutaneous (sc) AT depots. We assessed serum adiponectin and adiponectin
      protein concentrations and the molecular weight forms in vc (mesenterial,
      omental, and retroperitoneal) and sc (sternum, tail-head, and withers) AT of
      primiparous dairy cows during early lactation. Primiparous German Holstein cows
      (n = 25) were divided into a control (CON) and a conjugated linoleic acid (CLA)
      group. From day 1 of lactation until slaughter, CLA cows were fed 100 g of a CLA
      supplement/d (approximately 6% of cis-9, trans-11 and trans-10, cis-12 isomers
      each), whereas the CON cows received 100 g of a fatty acid mixture/d instead of
      CLA. Blood samples from all animals were collected from 3 wk before calving until
      slaughter on day 1 (n = 5, CON cows), 42 (n = 5 each of CON and CLA cows), and
      105 (n = 5 each of CON and CLA cows) of lactation when samples from different AT
      depots were obtained. Adiponectin was measured in serum and tissue by ELISA. In
      all AT depots adiponectin concentrations were lowest on day 1 than on day 42 and
      day 105, and circulating adiponectin reached a nadir around parturition.
      Retroperitoneal AT had the lowest adiponectin concentrations; however, when
      taking total depot mass into consideration, the portion of circulating
      adiponectin was higher in vc than sc AT. Serum adiponectin was positively
      correlated with adiponectin protein concentrations but not with the mRNA
      abundance in all fat depots. The CLA supplementation did not affect adiponectin
      concentrations in AT depots. Furthermore, inverse associations between
      circulating adiponectin and measures of body condition (empty body weight, back
      fat thickness, and vc AT mass) were observed. In all AT depots at each time,
      adiponectin was present as high (approximately 300 kDa) and medium (approximately
      150 kDa) molecular weight complexes similar to that of the blood serum. These
      data suggest differential contribution of AT depots to circulating adiponectin. 

PMID- 24462181
TI  - Development of model for analysing respective collections of intended
      hematopoietic stem cells and harvests of unintended mature cells in apheresis for
      autologous hematopoietic stem cell collection.
AB  - Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic
      autologous stem cell transplantation (APBSCT) can be collected by processing
      several blood volumes (BVs) in leukapheresis sessions. However, this may cause
      granulocyte harvest in graft and decrease in patient's platelet blood level. Both
      consequences may induce disturbances in patient. One apheresis team's current
      purpose is to improve HSC collection by increasing HSC collection and prevent
      increase in granulocyte and platelet harvests. Before improving HSC collection it
      seemed important to know more about the way to harvest these types of cells. The
      purpose of our study was to develop a simple model for analysing respective
      collections of intended CD34+ cells among HSC (designated here as HSC) and
      harvests of unintended platelets or granulocytes among mature cells (designated
      here as mature cells) considering the number of BVs processed and factors likely
      to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in
      59 leukapheresis sessions and analysed corresponding collections and harvests
      with a referent device (COBE Spectra). First we analysed the amounts of HSC
      collected and mature cells harvested and second the evolution of the respective
      shares of HSC and mature cells collected or harvested throughout the BV
      processes. HSC collections and mature cell harvests increased globally (p<0.0001)
      and their respective shares remained stable throughout the BV processes (p non
      significant). We analysed the role of intrinsic (patient's features) and
      extrinsic (features before starting leukapheresis sessions) factors in
      collections and harvests, which showed that only pre-leukapheresis blood levels
      (CD34+cells and platelets) influenced both cell collections and harvests
      (CD34+cells and platelets) (p<0.001) and shares of HSC collections and mature
      unintended cells harvests (p<0.001) throughout the BV processes. Altogether, our
      results suggested that the main factors likely to influence intended HSC
      collections or unintended mature cell harvests were pre-leukapheresis blood cell
      levels. Our model was meant to assist apheresis teams in analysing shares of HSC
      collected and mature cells harvested with new devices or with new types of HSC
      mobilization. 

PMID- 24462182
TI  - FimY of Salmonella enterica serovar Typhimurium functions as a DNA-binding
      protein and binds the fimZ promoter.
AB  - Salmonella enterica serovar Typhimurium produces type 1 fimbriae with binding
      specificity to mannose residues. Elements involved in fimbrial structural
      biosynthesis, transport, and regulation are encoded by the fim gene cluster.
      FimZ, FimY, FimW, STM0551, and an arginine transfer RNA (fimU) were previously
      demonstrated to regulate fimbrial expression. The amino acid sequences of the C
      terminal portion of FimY revealed similarity with those of LuxR-like proteins.
      Electrophoretic mobility shift assays indicated that FimY possessed DNA-binding
      capacity and bound a 605-bp DNA fragment spanning the intergenic region between
      fimY and fimZ, while a FimY protein harboring a double mutation in the C-terminal
      helix-turn-helix region containing a glycine (G) to aspartate (D) substitution at
      residue 189 and isoleucine (I) to lysine (K) substitution at residue 195 lost its
      ability to bind this DNA fragment. A lux box sequence (5'-TCTGTTATTACATAACAAATACT
      3') within the fimZ promoter was required for binding. None of the DNA fragments
      derived from the promoters for fimA, fimY, or fimW was shifted by FimY. Pull-down
      assays showed that there were physical protein/protein interactions between FimY
      and FimZ. We propose that in the regulatory circuit of type 1 fimbriae, FimY
      functions as a DNA-binding protein to activate fimZ, and a FimY-FimZ protein
      complex may form to regulate other fim genes. Confirming these proposals requires
      further study. 

PMID- 24462184
TI  - Campylobacter infection in wild artiodactyl species from southern Spain:
      occurrence, risk factors and antimicrobial susceptibility.
AB  - A cross-sectional study was performed to assess the occurrence of Campylobacter
      species and to identify potential associated risk factors for wild artiodactyl
      species in southern Spain. Campylobacter species were isolated in 55 of 363
      (15.2%) faecal samples. Campylobacter was identified in faeces from wild boar
      (49/126; 38.9%), red deer (5/179; 2.8%) and mouflon (1/13; 7.7%) but not from
      fallow deer (0/45). The isolated Campylobacter species were identified as C.
      jejuni (2 isolates; 3.6%), C. coli (11 isolates; 20.0%) and C. lanienae (37
      isolates; 67.3%). Five isolates (9.1%) could not be identified at the species
      level. This report is the first to describe C. lanienae infection in wild
      ruminant species. Resistance to erythromycin (4.8%), ciprofloxacin (37.5%),
      tetracycline (52.9%) and streptomycin (55%) were detected. C. lanienae presented
      a significantly higher number of susceptible isolates to ciprofloxacin and
      tetracycline than C. coli. Due to the low number of positive wild ruminants, a
      Generalised Estimating Equations model was only carried out for wild boar. The
      model indicated that the risk factors associated with Campylobacter infection
      were the density of wild boar (>10/100ha) (OR: 3.05; CI95%: 2.2-4.3), the
      presence of artificial waterholes (OR: 3.67; CI95%: 1.3-10.5) and the winter
      season (OR: 3.30; CI95%: 1.9-5.8). Campylobacter infection is widespread in wild
      boar populations in southern Spain. These findings suggest that wild
      artiodactyls, particularly wild boar, constitute a reservoir of Campylobacter
      species, including resistant and multi-resistant strains, which may be of public
      health concern. 

PMID- 24462183
TI  - Japanese and non-Japanese patient outcomes in the PLATINUM randomized trial
      comparing the PROMUS Element and XIENCE V everolimus-eluting stents.
AB  - BACKGROUND: The PLATINUM randomized trial enrolled 1530 patients treated with
      either the platinum chromium PROMUS Element everolimus-eluting stent (PtCr-EES;
      Boston Scientific, Natick, MA, USA) or the predicate cobalt chromium
      PROMUS/XIENCE V EES (CoCr-EES; manufactured as XIENCE V by Abbott Vascular, Santa
      Clara, CA, USA also distributed as PROMUS by Boston Scientific), including 124
      patients from Japanese sites. This substudy examines 2-year outcomes in the
      Japanese and non-Japanese cohorts. METHODS: Patients with 1 or 2 de novo native
      coronary artery lesions (baseline vessel diameter >=2.50mm to <=4.25mm and length
      <=24mm) were randomized 1:1 to PtCr-EES (N=63 patients in Japan) versus CoCr-EES
      (N=61 patients in Japan). RESULTS: Several significant differences were noted in
      baseline demographics, lesion characteristics, and procedural technique between
      Japanese and non-Japanese patients, including longer fluoroscopy time, less use
      of contrast, and greater post-dilatation usage and maximum pressure in Japan.
      Dual antiplatelet usage at 2 years was also higher in Japan. Despite these
      differences, the 2-year rates of target lesion failure were comparable in
      patients treated with PtCr-EES and CoCr-EES both in Japan (3.2% vs 5.0%
      respectively, p=0.68) and outside Japan (4.7% vs 5.9% respectively, p=0.33; p for
      interaction=0.82). CONCLUSIONS: This PLATINUM study subanalysis suggests that the
      PtCr-EES and CoCr-EES provide comparable safety and efficacy in both Japanese and
      non-Japanese patients.

PMID- 24462185
TI  - [Carpal tunnel syndrome and "trigger wrist" revealing a tendinous sheath
      fibroma].
AB  - The tendinous sheath fibroma (TSF) is a rare benign tumor, exceptionally
      responsible for carpal tunnel syndrome and "trigger" wrist: we found this
      association less than ten times in the English and French literature. We report
      the case of a 63-year-old right-handed carpenter who featured a triggering
      phenomenon of the right wrist during the flexion-extension movements and
      compression of the median nerve at the carpal tunnel, secondary to a TSF of the
      flexor digitorum superficialis. The diagnosis was suspected at the sonography and
      MRI, the tumor was excised and proven histologically to be a TSF. One year later,
      the patient remained free of symptoms. 

PMID- 24462186
TI  - A microtubule-associated zinc finger protein, BuGZ, regulates mitotic chromosome
      alignment by ensuring Bub3 stability and kinetochore targeting.
AB  - Equal chromosome segregation requires proper assembly of many proteins, including
      Bub3, onto kinetochores to promote kinetochore-microtubule interactions. By
      screening for mitotic regulators in the spindle envelope and matrix (Spemix), we
      identify a conserved Bub3 interacting and GLE-2-binding sequence (GLEBS)
      containing ZNF207 (BuGZ) that associates with spindle microtubules and regulates
      chromosome alignment. Using its conserved GLEBS, BuGZ directly binds and
      stabilizes Bub3. BuGZ also uses its microtubule-binding domain to enhance the
      loading of Bub3 to kinetochores that have assumed initial interactions with
      microtubules in prometaphase. This enhanced Bub3 loading is required for proper
      chromosome alignment and metaphase to anaphase progression. Interestingly, we
      show that microtubules are required for the highest kinetochore loading of Bub3,
      BubR1, and CENP-E during prometaphase. These findings suggest that BuGZ not only
      serves as a molecular chaperone for Bub3 but also enhances its loading onto
      kinetochores during prometaphase in a microtubule-dependent manner to promote
      chromosome alignment. 

PMID- 24462188
TI  - Midwives' perceptions of organisational structures and processes influencing
      their ability to provide caseload care to socially disadvantaged and vulnerable
      women.
AB  - OBJECTIVE: This study examined midwives' perceptions of organisational structures
      and processes of care when working in a caseload model (Midwifery Group Practice
      MGP) for socially disadvantaged and vulnerable childbearing women. DESIGN: This
      study used Donabedian's theoretical framework for evaluating the quality of
      health care provision. Of the 17 eligible midwives, 15 participated in focus
      group discussions and two others provided written comments. Thematic analysis was
      guided by three headings; clinical outcomes, processes of care and organisational
      structure. FINDINGS: Midwives believed they provided an excellent service to
      socially disadvantaged and vulnerable childbearing women. Midwives gained
      satisfaction from working in partnership with women, working across their full
      scope of practice, and making a difference to the women. However the midwives
      perceived the MGP was situated within an organisation that was hostile to the
      caseload model of care. Midwives felt frustrated and distressed by a lack of
      organisational support for the model and a culture of blame dominated by
      medicine. A lack of material resources and no identified office space created
      feelings akin to 'homelessness'. Together these challenges threatened the
      cohesiveness of the MGP and undermined midwives' ability to advocate for women
      and keep birth normal. KEY CONCLUSIONS: If access to caseload midwifery care for
      women with diverse backgrounds and circumstances is to be enhanced, then
      mechanisms need to be implemented to ensure organisational structures and
      processes are developed to sustain midwives in the provision of 'best practice'
      maternity care. IMPLICATIONS FOR PRACTICE: Women accessing midwifery caseload
      care have excellent maternal and newborn outcomes. However there remains limited
      understanding of the impact of organisational structures and processes of care on
      clinical outcomes.

PMID- 24462189
TI  - Being safe practitioners and safe mothers: a critical ethnography of continuity
      of care midwifery in Australia.
AB  - OBJECTIVE: To examine how midwives and women within a continuity of care
      midwifery programme in Australia conceptualised childbirth risk and the
      influences of these conceptualisations on women's choices and midwives' practice.
      DESIGN AND SETTING: A critical ethnography within a community-based continuity of
      midwifery care programme, including semi-structured interviews and the
      observation of sequential antenatal appointments. PARTICIPANTS: Eight midwives,
      an obstetrician and 17 women. FINDINGS: The midwives assumed a risk-negotiator
      role in order to mediate relationships between women and hospital-based maternity
      staff. The role of risk-negotiator relied profoundly on the trust engendered in
      their relationships with women. Trust within the mother-midwife relationship
      furthermore acted as a catalyst for complex processes of identity work which, in
      turn, allowed midwives to manipulate existing obstetric risk hierarchies and
      effectively re-order risk conceptualisations. In establishing and maintaining
      identities of 'safe practitioner' and 'safe mother', greater scope for the
      negotiation of normal within a context of obstetric risk was achieved. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The effects of obstetric risk
      practices can be mitigated when trust within the mother-midwife relationship acts
      as a catalyst for identity work and supports the midwife's role as a risk
      negotiator. The achievement of mutual identity-work through the midwives' role as
      risk-negotiator can contribute to improved outcomes for women receiving
      continuity of care. However, midwives needed to perform the role of risk
      negotiator while simultaneously negotiating their professional credibility in a
      setting that construed their practice as risky.

PMID- 24462187
TI  - BuGZ is required for Bub3 stability, Bub1 kinetochore function, and chromosome
      alignment.
AB  - During mitosis, the spindle assembly checkpoint (SAC) monitors the attachment of
      kinetochores (KTs) to the plus ends of spindle microtubules (MTs) and prevents
      anaphase onset until chromosomes are aligned and KTs are under proper tension.
      Here, we identify a SAC component, BuGZ/ZNF207, from an RNAi viability screen in
      human glioblastoma multiforme (GBM) brain tumor stem cells. BuGZ binds to and
      stabilizes Bub3 during interphase and mitosis through a highly conserved GLE2p
      binding sequence (GLEBS) domain. Inhibition of BuGZ results in loss of both Bub3
      and its binding partner Bub1 from KTs, reduction of Bub1-dependent
      phosphorylation of centromeric histone H2A, attenuation of KT-based Aurora B
      kinase activity, and lethal chromosome congression defects in cancer cells.
      Phylogenetic analysis indicates that BuGZ orthologs are highly conserved among
      eukaryotes, but are conspicuously absent from budding and fission yeasts. These
      findings suggest that BuGZ has evolved to facilitate Bub3 activity and chromosome
      congression in higher eukaryotes. 

PMID- 24462190
TI  - Managing the manager: gut microbes, stem cells and metabolism.
AB  - One major discovery of the last decade in the field of metabolic diseases is that
      the microorganisms comprising the gut microbiota are now considered a metabolic
      "organ", modulating multiple functions of the host, such as intestinal immune
      system maturation, adiposity, cardiac metabolism, liver triglyceride storage, and
      brain development and behaviour. The corresponding mechanisms involve increased
      energy harvesting through the production by microbiota of short-chain fatty acids
      for use by the host, and the release of pro-inflammatory compounds, such as
      lipopolysaccharide (LPS), flagellin and peptidoglycan. In particular, a high-fat
      diet (HFD) modifies gut microbiota, resulting in an increase of plasma LPS levels
      known as "metabolic endotoxaemia", a major driver of the onset of metabolic
      diseases through a CD14-dependent mechanism. The LPS-sensitive cell types can be
      seen within bone marrow-derived cells (BMC), which are involved in the
      development of inflammation in the adipose tissue of obese and type 2 diabetic
      mice. Furthermore, the expression of LPS receptor/cofactor CD14 cells from the
      stromal vascular fraction of adipose depots can also be directly targeted by LPS
      to initiate precursor cell development and adiposity. Moreover, data from the
      literature also indicate an impact of gut microbiota on intestinal stem cells.
      Thus, this mini review presents the experimental evidence supporting a
      relationship between gut microbiota and stem cells as a new axis of metabolic
      homoeostasis control. 

PMID- 24462192
TI  - Effects of quarter individual and conventional milking systems on teat condition.
AB  - An on-farm experiment was performed to investigate the effects of two milking
      systems on teat condition. An auto-tandem milking parlor made by GEA((r)) with a
      conventional milking cluster (CON) and a single tube milking system called
      MultiLactor((r)) (MULTI) from Siliconform GmbH were tested. For both milking
      system, in total 73 animals were milked over a period of seven months. To assess
      the effect of milking on teat condition, each teat was scored according to teat
      condition evaluation systems. To evaluate teat condition, the teat color, ring
      formation at the teat base and formation of teat hyperkeratosis were assessed.
      The evaluation was conducted once a month after milking. The collected data were
      then statistically analyzed with generalized linear mixed models. The only
      differences found between the two milking systems occurred with respect to their
      effect on teat color. MULTI showed significantly better scores compared to CON.
      There were no significant differences between the milking systems with regard to
      teat-end hyperkeratosis and ring formation at the teat base. 

PMID- 24462193
TI  - Seasonal shifts in bacteria associated with Jersey cows on a small dairy farm and
      the potential for bedding choice and low levels of iodine use to inhibit mastitic
      pathogens.
AB  - Milk products from small dairies are increasingly in demand, as access to pasture
      provides benefits to the cow, consumer, and environment. The productivity and
      profitability of small dairy farms particularly rely on the prevention of
      infectious diseases. Cattle on seasonal grazing dairies live primarily outdoors
      until inclement weather warrants relocation indoors. While shifts in the amounts
      of bacteria associated with livestock may be expected from this transition,
      potentially increasing risks for infectious diseases, changes in bacteria levels
      on cows relocated to indoor facilities have not been well-studied. In addition,
      the optimal use of bedding materials and iodine are critical in bovine infectious
      diseases prevention. However, the antibacterial potential of bedding material
      with high polyphenol content or low concentrations of iodine, are poorly
      understood. Cow teats were swabbed and total bacteria and coliform counts, as
      well as extracellular enzyme activities (EEA) were utilized to assess shifts in
      bacterial levels on cows at pasture and then housed indoors. To test the
      antibacterial efficacy of bedding materials, as well as low concentrations of
      povidone-iodine, growth curves with laboratory strains of Staphylococcus aureus
      and Klebsiella pneumoniae, as well as S. aureus isolated from a dairy farm, were
      performed with three concentrations of red cedar shavings or iodine. Post hoc
      multiple comparisons indicated that total bacteria, coliform, and beta
      galactosidase activities were significantly greater among cows housed indoors
      compared to bacterial samples from cows at pasture. Laboratory strains of S.
      aureus, but not K. pneumoniae, were significantly inhibited by moderate and high
      treatments of red cedar shavings, while S. aureus isolated from a dairy were
      inhibited by the high treatment only. All low iodine concentrations significantly
      inhibited each bacterial strain investigated. These results may help optimize
      strategies for the prevention of infectious diseases of bovine udders critical to
      the productivity and profitability of small dairies. 

PMID- 24462191
TI  - Using quantitative disease dynamics as a tool for guiding response to avian
      influenza in poultry in the United States of America.
AB  - Wild birds are the primary source of genetic diversity for influenza A viruses
      that eventually emerge in poultry and humans. Much progress has been made in the
      descriptive ecology of avian influenza viruses (AIVs), but contributions are less
      evident from quantitative studies (e.g., those including disease dynamic models).
      Transmission between host species, individuals and flocks has not been measured
      with sufficient accuracy to allow robust quantitative evaluation of alternate
      control protocols. We focused on the United States of America (USA) as a case
      study for determining the state of our quantitative knowledge of potential AIV
      emergence processes from wild hosts to poultry. We identified priorities for
      quantitative research that would build on existing tools for responding to AIV in
      poultry and concluded that the following knowledge gaps can be addressed with
      current empirical data: (1) quantification of the spatio-temporal relationships
      between AIV prevalence in wild hosts and poultry populations, (2) understanding
      how the structure of different poultry sectors impacts within-flock transmission,
      (3) determining mechanisms and rates of between-farm spread, and (4) validating
      current policy-decision tools with data. The modeling studies we recommend will
      improve our mechanistic understanding of potential AIV transmission patterns in
      USA poultry, leading to improved measures of accuracy and reduced uncertainty
      when evaluating alternative control strategies. 

PMID- 24462194
TI  - Risk assessment and cost-effectiveness of animal health certification methods for
      livestock export in Somalia.
AB  - Livestock export is vital to the Somali economy. To protect Somali livestock
      exports from costly import bans used to control the international spread of
      disease, better certification of livestock health status is required. We
      performed quantitative risk assessment and cost-effectiveness analysis on
      different health certification protocols for Somali livestock exports for six
      transboundary diseases. Examining stock at regional markets alone without port
      inspection and quarantine was inexpensive but was ineffective for all but
      contagious bovine pleuropneumonia, contagious caprine pleuropneumonia and peste
      des petits ruminants. While extended pre-export quarantine improves detection of
      infections that cause clinical disease, if biosecurity is suboptimal quarantine
      provides an opportunity for transmission and increased risk. Clinical
      examination, laboratory screening and vaccination of animals for key diseases
      before entry to the quarantine station reduced the risk of an exported animal
      being infected. If vaccination could be reliably performed weeks before arrival
      at quarantine its effect would be greatly enhanced. The optimal certification
      method depends on the disease. Laboratory diagnostic testing was particularly
      important for detecting infections with limited clinical signs in male animals
      (only males are exported); for Rift Valley fever (RVF) the probability of
      detection was 99% or 0% with and without testing. Based on our findings animal
      inspection and certification at regional markets combined with quarantine
      inspection and certification would reduce the risk of exporting infected animals
      and enhance disease control at the regional level. This is especially so for key
      priority diseases, that is RVF, foot-and-mouth disease and Brucellosis. Increased
      data collection and testing should be applied at point of production and export. 

PMID- 24462195
TI  - Craniofacial variation, body size and ecological factors in aboriginal
      populations from central Patagonia (2000-200 years B.P.).
AB  - Previous studies have shown that ecological factors had a significant role in
      shaping the patterns of craniofacial variation among South American populations.
      Here, we evaluate whether temperature and diet contributed to facial
      diversification in small geographic areas. Facial size and shape of 9
      osteological samples from central Patagonia (Argentina) were described using 2D
      landmarks and semilandmarks. Data on mean annual temperature, diet composition
      (delta(13)C and delta(15)N values) and femoral head maximum breadth, used as a
      proxy of body mass, were obtained for each sample. We then tested the association
      of body mass and the ecological variables with facial morphology using spatial
      regression techniques and a model selection approach. Akaike Information
      Criterion produced disparate results for both components of facial morphology.
      The best model for facial size included temperature and body mass proxy, and
      accounted for more than 80% of variation in size. Lower temperatures were related
      to larger facial sizes. Body mass was negatively associated with facial size and
      showed no relationship with the temperature. This suggests a relatively
      independent variation of cranial traits and body mass at the spatial scale
      studied here. Facial shape was not associated with the temperature or diet
      composition, contrasting with the patterns observed at larger spatial scales. Our
      results point out that the effect of climatic variables on cranial traits might
      be a source of morphological differentiation not only at large scales but also in
      small geographic areas, and that size and shape display a differential
      preservation of environmental signals. 

PMID- 24462196
TI  - Atrial fibrillation from the pathologist's perspective.
AB  - Atrial fibrillation (AF), the most common sustained cardiac arrhythmia
      encountered in clinical practice, is associated with increased morbidity and
      mortality. Electrophysiologically, it is characterized by a high rate of
      asynchronous atrial cell depolarization causing a loss of atrial contractile
      function and irregular ventricular rates. For a long time, AF was considered as a
      pure functional disorder without any structural background. Only in recent years,
      have new mapping and imaging techniques identified atrial locations, which are
      very often involved in the initiation and maintenance of this supraventricular
      arrhythmia (i.e. the distal portion of the pulmonary veins and the surrounding
      atrial myocardium). Morphological analysis of these myocardial sites has
      demonstrated significant structural remodeling as well as paved the way for
      further knowledge of AF natural history, pathogenesis, and treatment. This
      architectural myocardial disarrangement is induced by the arrhythmia itself and
      the very frequently associated cardiovascular disorders. At the same time, the
      structural remodeling is also capable of sustaining AF, thereby creating a sort
      of pathogenetic vicious circle. This review focuses on current understanding
      about the structural and genetic bases of AF with reference to their
      classification, pathogenesis, and clinical implications. 

PMID- 24462197
TI  - Stress cardiomyopathy: yet another type of neurocardiogenic injury: 'stress
      cardiomyopathy'.
AB  - Tako-tsubo syndrome pertains to rare acquired cardiomyopathies, characterized by
      left ventricular dyskinesia and symptomatology typical for acute myocardial
      infarction (AMI). Despite its low incidence and relatively benign course, stress
      cardiomyopathy should be thoroughly differentiated from AMI. The importance of
      tako-tsubo consists of the fact that its manifestation initially resembles AMI.
      Despite seemingly low incidence of tako-tsubo, acute coronary syndromes globally
      constitute a major epidemiological issue and both clinical entities should be
      accurately differentiated. Many patients present with only mild troponin release,
      certain extent of regional wall motion abnormalities (RWMA) and absence of
      hemodynamically significant coronary artery stenosis. In such instances, a
      careful interview aimed at preceding emotional or physical traumatic event should
      be undertaken. The subsequent verification of the diagnosis is based upon prompt
      recovery of contractile function. Although precise diagnostic criteria were
      formulated, symptomatology of tako-tsubo might be clinically misleading due to
      the possibility of concomitant coronary vasospasm, atypical pattern of RWMA and
      presence of non-significant coronary disease. For this reason, its exact rate
      might be underestimated. Stress cardiomyopathy reflects merely a single aspect of
      a much wider range of neurocardiogenic injury, which encompasses cardiac
      dysfunction associated with subarachnoid hemorrhage, intracranial hypertension
      and cerebral ischemia. Both psychological and physical insult to central nervous
      system may trigger a disastrous response of sympathetic nervous system,
      eventually leading to end-organ catecholamine-mediated damage. This review sought
      to delineate the phenomenon of tako-tsubo cardiomyopathy and deliver evidence for
      common pathophysiology of the broad spectrum of neurocardiogenic injury. 

PMID- 24462198
TI  - Prediction of blood culture results by measuring procalcitonin levels and other
      inflammatory biomarkers.
AB  - BACKGROUND: It would be helpful if we could predict positive or negative blood
      culture results. This study considered the usefulness of measuring procalcitonin
      (PCT) level and standard clinical biomarkers such as white blood cell (WBC)
      count, C-reactive protein (CRP) level, and platelet (PLT) count to predict blood
      culture results. METHOD: We retrospectively analyzed the data from 422 specimens
      collected at our emergency center within the preceding 36 consecutive months.
      Primary component analysis (PCA) was used for detecting the degree of the
      relational contribution of each of the 4 biomarkers to the blood culture results.
      RESULTS: Procalcitonin alone (cut-off value, 0.5 ng/mL) yielded a positive blood
      culture rate of 34.0%. Procalcitonin plus 3 biomarkers (WBC, CRP, and PLT)
      analyzed by PCA yielded 45.9% or 35.3% when a case was in the first or fourth
      quadrant, which was significantly higher than cases in the second or third
      quadrant. Primary component analysis also revealed that positive blood culture
      results were mainly affected by primary component 1, to which PCT and PLT (not
      WBC or CRP) predominantly contribute. CONCLUSION: Although it is difficult to
      predict blood culture results, even using 4 biomarkers analyzed by PCA, our new
      finding that blood culture results are affected not by WBC and CRP, but mainly by
      PCT and PLT, might help explain the mechanism of sepsis.

PMID- 24462199
TI  - Reduction of chalcogen oxyanions and generation of nanoprecipitates by the
      photosynthetic bacterium Rhodobacter capsulatus.
AB  - The facultative photosynthetic bacterium Rhodobacter capsulatus is characterized
      in its interaction with the toxic oxyanions tellurite (Te(IV)) and selenite
      (Se(IV)) by a highly variable level of resistance that is dependent on the growth
      mode making this bacterium an ideal organism for the study of the microbial
      interaction with chalcogens. As we have reported in the past, while the oxyanion
      tellurite is taken up by R. capsulatus cells via acetate permease and it is
      reduced to Te(0) in the cytoplasm in the form of splinter-like black
      intracellular deposits no clear mechanism was described for Se(0) precipitation.
      Here, we present the first report on the biotransformation of tellurium and
      selenium oxyanions into extracellular Te(0) and Se(0)nanoprecipitates (NPs) by
      anaerobic photosynthetically growing cultures of R. capsulatus as a function of
      exogenously added redox-mediator lawsone, i.e. 2-hydroxy-1,4-naphthoquinone. The
      NPs formation was dependent on the carbon source used for the bacterial growth
      and the rate of chalcogen reduction was constant at different lawsone
      concentrations, in line with a catalytic role for the redox mediator. X-ray
      diffraction (XRD) analysis demonstrated the Te(0) and Se(0) nature of the
      nanoparticles. 

PMID- 24462200
TI  - Spindle assembly factor protection.
AB  - In this issue, Song et al. (2014) describe how microtubules and the RAN
      GTPase/importin-beta system collaborate to control timing of HURP action and its
      turnover via the anaphase promoting complex (APC)-proteasome system, thereby
      ensuring temporal control of late mitotic events.

PMID- 24462201
TI  - Interactions between autophagy receptors and ubiquitin-like proteins form the
      molecular basis for selective autophagy.
AB  - Selective autophagy ensures recognition and removal of various cytosolic cargoes.
      Hence, aggregated proteins, damaged organelles, or pathogens are enclosed into
      the double-membrane vesicle, the autophagosome, and delivered to the lysosome for
      degradation. This process is mediated by selective autophagy receptors, such as
      p62/SQSTM1. These proteins recognize autophagic cargo and, via binding to small
      ubiquitin-like modifiers (UBLs)--Atg8/LC3/GABARAPs and ATG5--mediate formation of
      selective autophagosomes. Recently, it was found that UBLs can directly engage
      the autophagosome nucleation machinery. Here, we review recent findings on
      selective autophagy and propose a model for selective autophagosome formation in
      close proximity to cargo.

PMID- 24462202
TI  - Microtubule-dependent regulation of mitotic protein degradation.
AB  - Accurate cell division depends on tightly regulated ubiquitylation events
      catalyzed by the anaphase-promoting complex (APC/C). Among its many substrates,
      the APC/C triggers the degradation of proteins that stabilize the mitotic
      spindle, and loss or accumulation of such spindle assembly factors can result in
      aneuploidy and cancer. Although critical for cell division, it has remained
      poorly understood how the timing of spindle assembly factor degradation is
      established during mitosis. Here, we report that active spindle assembly factors
      are protected from APC/C-dependent degradation by microtubules. In contrast,
      those molecules that are not bound to microtubules are highly susceptible to
      proteolysis and turned over immediately after APC/C activation. The correct
      timing of spindle assembly factor degradation, as achieved by this regulatory
      circuit, is required for accurate spindle structure and function. We propose that
      the localized stabilization of APC/C substrates provides a mechanism for the
      selective disposal of cell-cycle regulators that have fulfilled their mitotic
      roles. 

PMID- 24462203
TI  - Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for
      interferon-induced antiviral activity.
AB  - RNase L is an ankyrin repeat domain-containing dual endoribonuclease-pseudokinase
      that is activated by unusual 2,'5'-oligoadenylate (2-5A) second messengers and
      which impedes viral infections in higher vertebrates. Despite its importance in
      interferon-regulated antiviral innate immunity, relatively little is known about
      its precise mechanism of action. Here we present a functional characterization of
      2.5 A and 3.25 A X-ray crystal and small-angle X-ray scattering structures of
      RNase L bound to a natural 2-5A activator with and without ADP or the
      nonhydrolysable ATP mimetic AMP-PNP. These studies reveal how recognition of 2-5A
      through interactions with the ankyrin repeat domain and the pseudokinase domain,
      together with nucleotide binding, imposes a rigid intertwined dimer configuration
      that is essential for RNase catalytic and antiviral functions. The involvement of
      the pseudokinase domain of RNase L in 2-5A sensing, nucleotide binding,
      dimerization, and ribonuclease functions highlights the evolutionary adaptability
      of the eukaryotic protein kinase fold.

PMID- 24462204
TI  - Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the
      Inactive X Chromosome.
AB  - During X chromosome inactivation (XCI), the Polycomb Repressive Complex 2 (PRC2)
      is thought to participate in the early maintenance of the inactive state.
      Although Xist RNA is essential for the recruitment of PRC2 to the X chromosome,
      the precise mechanism remains unclear. Here, we demonstrate that the PRC2
      cofactor Jarid2 is an important mediator of Xist-induced PRC2 targeting. The
      region containing the conserved B and F repeats of Xist is critical for Jarid2
      recruitment via its unique N-terminal domain. Xist-induced Jarid2 recruitment
      occurs chromosome-wide independently of a functional PRC2 complex, unlike at
      other parts of the genome, such as CG-rich regions, where Jarid2 and PRC2 binding
      are interdependent. Conversely, we show that Jarid2 loss prevents efficient PRC2
      and H3K27me3 enrichment to Xist-coated chromatin. Jarid2 thus represents an
      important intermediate between PRC2 and Xist RNA for the initial targeting of the
      PRC2 complex to the X chromosome during onset of XCI.

PMID- 24462205
TI  - Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive
      inhibitors.
AB  - The stability and activity of numerous signaling proteins in both normal and
      cancer cells depends on the dimeric molecular chaperone heat shock protein 90
      (Hsp90). Hsp90's function is coupled to ATP binding and hydrolysis and requires a
      series of conformational changes that are regulated by cochaperones and numerous
      posttranslational modifications (PTMs). SUMOylation is one of the least
      understood Hsp90 PTMs. Here, we show that asymmetric SUMOylation of a conserved
      lysine residue in the N domain of both yeast (K178) and human (K191) Hsp90
      facilitates both recruitment of the adenosine triphosphatase (ATPase)-activating
      cochaperone Aha1 and, unexpectedly, the binding of Hsp90 inhibitors, suggesting
      that these drugs associate preferentially with Hsp90 proteins that are actively
      engaged in the chaperone cycle. Importantly, cellular transformation is
      accompanied by elevated steady-state N domain SUMOylation, and increased Hsp90
      SUMOylation sensitizes yeast and mammalian cells to Hsp90 inhibitors, providing a
      mechanism to explain the sensitivity of cancer cells to these drugs. 

PMID- 24462206
TI  - Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports
      a two-step ATP hydrolysis mechanism.
AB  - While structural symmetry is a prevailing feature of homo-oligomeric proteins,
      asymmetry provides unique mechanistic opportunities. We present the crystal
      structure of full-length TRAP1, the mitochondrial Hsp90 molecular chaperone, in a
      catalytically active closed state. The TRAP1 homodimer adopts a distinct,
      asymmetric conformation, where one protomer is reconfigured via a helix swap at
      the middle:C-terminal domain (MD:CTD) interface. This interface plays a critical
      role in client binding. Solution methods validate the asymmetry and show
      extension to Hsp90 homologs. Point mutations that disrupt unique contacts at each
      MD:CTD interface reduce catalytic activity and substrate binding and demonstrate
      that each protomer needs access to both conformations. Crystallographic data on a
      dimeric NTD:MD fragment suggests that asymmetry arises from strain induced by
      simultaneous NTD and CTD dimerization. The observed asymmetry provides the
      potential for an additional step in the ATPase cycle, allowing sequential ATP
      hydrolysis steps to drive both client remodeling and client release.

PMID- 24462207
TI  - Designed Hsp90 heterodimers reveal an asymmetric ATPase-driven mechanism in vivo.
AB  - Hsp90 is a homodimeric ATPase that is essential in eukaryotes for the maturation
      of client proteins frequently involved in signal transduction, including many
      kinases and nuclear steroid hormone receptors. Competitive inhibitors of ATP
      binding to Hsp90 prevent client maturation and show promise as anticancer agents
      in clinical trials. However, the role of ATP binding and hydrolysis in each
      subunit of the Hsp90 dimer has been difficult to investigate because of an
      inability to assemble and study dimers of defined composition. We used protein
      engineering to generate functional Hsp90 subunits that preferentially assemble as
      heterodimers. We analyzed dimers wherein one subunit harbors a disruptive
      mutation and observed that ATP binding by both subunits is essential for function
      in yeast, whereas ATP hydrolysis is only required in one subunit. These findings
      demonstrate important functional contributions from both symmetric and asymmetric
      Hsp90 dimers and provide valuable reagents for future investigations of Hsp90
      mechanism.

PMID- 24462209
TI  - Organized breast screening: Answers to recurring controversies.
AB  - The reduction in mortality specifically from breast cancer, demonstrated in the
      major meta-analyses in the 1980s resulted in public health breast cancer
      screening programs being set up in many countries, including France. Recent
      publications have challenged the usefulness of screening, by insisting in
      particular on the negative effects of overdiagnosis and the lack of any
      significant impact on mortality. From analysis of the literature and particularly
      independent reviews published in 2012, we provide some answers for doctors faced
      with the legitimate concerns of women. These studies confirm that screening in
      the right age group reduces specific mortality by at least 20% at a cost of
      overdiagnosis estimated at between 1 and 15%. 

PMID- 24462208
TI  - PAXT-1 promotes XRN2 activity by stabilizing it through a conserved domain.
AB  - XRN2 is an essential eukaryotic exoribonuclease that processes and degrades
      various substrates. Here we identify the previously uncharacterized protein
      R05D11.6/PAXT-1 as a subunit of an XRN2 complex in C. elegans. Targeted paxt-1
      inactivation through TALEN-mediated genome editing reduces XRN2 levels, decreases
      miRNA turnover activity, and results in worm death, which can be averted by
      overexpressing xrn-2. Hence, stabilization of XRN2 is a major function of PAXT-1.
      A truncated PAXT-1 protein retaining a predicted domain of unknown function
      (DUF3469) suffices to restore viability to paxt-1 mutant animals, elevates XRN2
      levels, and binds to XRN2. This domain occurs in additional metazoan proteins and
      mediates interaction of human CDKN2AIP/CARF and NKRF/NRF with XRN2. Thus, we have
      identified a bona fide XRN2-binding domain (XTBD) that can link different
      proteins, and possibly functionalities, to XRN2.

PMID- 24462210
TI  - Phylogenomics for drug-resistant Neisseria gonorrhoeae.

PMID- 24462211
TI  - Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to
      cefixime in the USA: a retrospective observational study.
AB  - BACKGROUND: The emergence of Neisseria gonorrhoeae with decreased susceptibility
      to extended spectrum cephalosporins raises the prospect of untreatable
      gonorrhoea. In the absence of new treatments, efforts to slow the increasing
      incidence of resistant gonococcus require insight into the factors that
      contribute to its emergence and spread. We assessed the relatedness between
      isolates in the USA and reconstructed likely spread of lineages through different
      sexual networks. METHODS: We sequenced the genomes of 236 isolates of N
      gonorrhoeae collected by the Centers for Disease Control and Prevention's
      Gonococcal Isolate Surveillance Project (GISP) from sentinel public sexually
      transmitted disease clinics in the USA, including 118 (97%) of the isolates from
      2009-10 in GISP with reduced susceptibility to cefixime (cef(RS)) and 118
      cefixime-susceptible isolates from GISP matched as closely as possible by
      location, collection date, and sexual orientation. We assessed the association
      between antimicrobial resistance genotype and phenotype and correlated
      phylogenetic clustering with location and sexual orientation. FINDINGS: Mosaic
      penA XXXIV had a high positive predictive value for cef(RS). We found that two of
      the 118 cef(RS) isolates lacked a mosaic penA allele, and rechecking showed that
      these two were susceptible to cefixime. Of the 116 remaining cef(RS) isolates,
      114 (98%) fell into two distinct lineages that have independently acquired mosaic
      penA allele XXXIV. A major lineage of cef(RS) strains spread eastward,
      predominantly through a sexual network of men who have sex with men. Eight of
      nine inferred transitions between sexual networks were introductions from men who
      have sex with men into the heterosexual population. INTERPRETATION: Genomic
      methods might aid efforts to slow the spread of antibiotic-resistant N
      gonorrhoeae through augmentation of gonococcal outbreak surveillance and
      identification of populations that could benefit from increased screening for
      asymptomatic infections.

PMID- 24462212
TI  - Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5
      HT neuronal function and dopamine release.
AB  - Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in
      rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported
      to induce sedative effects. In this study, we demonstrated that limonene
      administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)
      induced head twitch response in mice. In rats, pretreatment with limonene
      decreased hyperlocomotion induced by methamphetamine injection. In addition,
      limonene reversed the increase in dopamine levels in the nucleus accumbens of
      rats given methamphetamine. These results suggest that limonene may inhibit
      stimulant-induced behavioral changes via regulating dopamine levels and 5-HT
      receptor function. 

PMID- 24462213
TI  - Effect of Tacrolimus on the pharmacokinetics of bioactive lignans of Wuzhi tablet
      (Schisandra sphenanthera extract) and the potential roles of CYP3A and P-gp.
AB  - We recently reported that Wuzhi tablet (WZ), a preparation of the ethanol extract
      of Wuweizi (Schisandra sphenanthera), had significant effects on blood
      concentrations of Tacrolimus (FK506) in renal transplant recipients and rats. The
      active lignans in WZ are schisandrin A, schisandrin B, schisandrin C, schisandrol
      A, schisandrol B, schisantherin A, and schisantherin B. Until now, whether the
      pharmacokinetics of these lignans in WZ would be affected by FK506 remained
      unknown. Therefore, this study aimed to investigate whether and how FK506
      affected pharmacokinetics of lignans in WZ in rats and the potential roles of
      CYP3A and P-gp. After a single oral co-administration of FK506 and WZ, the blood
      concentration of lignans in WZ was decreased by FK506; furthermore, the AUC of
      schisantherin A, schisandrin A, schisandrol A and schisandrol B was only 64.5%,
      47.2%, 55.1% and 57.4% of that of WZ alone group, respectively. Transport study
      in Caco-2 cells showed that these lignans were not substrates of P-gp, suggesting
      decreased blood concentration of lignans by FK506 was not via P-gp pathway.
      Metabolism study in the human recombinant CYP 3A showed that these lignans had
      higher affinity to CYP3A than that of FK506, and thus had a stronger CYP3A
      mediated metabolism. It was concluded that the blood concentrations of these
      lignans were decreased and their CYP3A-mediated metabolisms were increased in the
      presence of FK506 since these lignans had higher affinity to CYP3A. 

PMID- 24462214
TI  - Apigenin 7-glucoside from Stachys tibetica Vatke and its anxiolytic effect in
      rats.
AB  - BACKGROUND: Stachys tibetica Vatke (Himalayan or mountain tea) grows abundantly
      in the tropical and subtropical locations of the world including India, Tibet and
      China. The traditional healers of Kargil and adjoining areas in Ladakh, Jammu and
      Kashmir in India use the drug to treat fever, cough, phobias and various mental
      disorders etc. in the form of a decoction or as a tea. Flavonoids are important
      components in most herbal teas and play an important role in the management of
      various brain disorders via mimicking the action of benzodiazepines or through
      benzodiazepine receptors. AIM OF THE STUDY: The present study aimed to isolate
      flavonoids from S. tibetica and to evaluate their anxiolytic potential in
      comparison to reference synthetic (diazepam) and natural (apigenin) molecules.
      MATERIALS AND METHODS: S. tibetica root powder was extracted with 95% methanol
      for about 72 h using a soxhlet apparatus and the resultant extract was subjected
      to isolation procedures, resulting in the isolation of apigenin 7-glucoside and
      characterisation by various physical and spectrometric analyses. Apigenin 7
      glucoside was evaluated for anxiolytic activity in rats in comparison with the
      reference compounds diazepam and apigenin using the elevated plus maze (EPM)
      model. RESULTS: Phytochemical investigations of S. tibetica revealed the presence
      of tannins, phenolics, flavonoids, saponins, glycosides and carbohydrates. A
      flavonoid glucoside, apigenin 7-glucoside was isolated for the first time from
      the roots of S. tibetica Vatke. The percentage of time spent and arm entries in
      the open arms was increased while the arms entries and duration of time spent in
      closed arms were decreased in the groups treated with apigenin 7-glucoside (which
      dose). In a similar fashion, diazepam and apigenin also exhibited anxiolytic
      activity (*p<0.05, **p<0.01). Apigenin 7-glucoside significantly decreased the
      percentage of head dips in EPM. Apigenin 7-glucoside showed anxiolytic potential
      comparable to the reference drugs apigenin and diazepam. CONCLUSION: Apigenin 7
      glucoside could be an important molecule for the treatment of anxiety and further
      studies are required to elucidate its possible mechanism of action.

PMID- 24462215
TI  - Anti-diabetic effect of a novel N-Trisaccharide isolated from Cucumis prophetarum
      on streptozotocin-nicotinamide induced type 2 diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cucumis prophetarum (L.) is used in traditional
      Indian medicine for the treatment of inflammation related problems. AIM OF THE
      STUDY: The present investigation was designed to study the effect of N
      Trisaccharide (a new compound isolated from the fruit of C. prophetarum (L.)) on
      hyperglycemia in streptozotocin (STZ)-nicotinamide (NA) induced type 2 diabetic
      rats. MATERIALS AND METHODS: Different doses of N-Trisaccharide (25 and 50
      mg/kgb.w.) were administered once daily for 28 days to STZ-NA induced diabetic
      rats. Plasma insulin and glycogen levels were measured. The activities of
      hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6
      phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase were
      measured. Further, histological studies on pancreas were also carried out.
      RESULTS: The active compound at doses of 25 and 50 mg/kgb.w. given orally for 14
      days showed 47.7% and 69.3% antihyperglycemic activity, respectively. Treatment
      at the same doses for 28 days provided complete protection against STZ-NA
      challenge (65 and 230 mg/kgb.w., respectively), intraperitoneally. N
      Trisaccharide significantly (p<=0.05) increased the plasma insulin and liver
      glycogen levels in diabetic rats. The altered enzyme activities of carbohydrate
      metabolism in the liver and kidney of the diabetic rats were significantly
      (p<=0.05) improved. Additionally, N-Trisaccharide increased glycogen synthase and
      decreased glycogen phosphorylase activity in diabetic rats. Histological studies
      confirmed an increase in insulin level is due to stimulation of injured
      pancreatic beta-cells. CONCLUSION: The results of the study suggested that N
      Trisaccharide possesses propitious effect on STZ-NA induced type 2 diabetes,
      indicating its usefulness in diabetes management.

PMID- 24462216
TI  - Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption
      and neurological injury in a rat model of cerebral ischemia/reperfusion through
      downregulation of aquaporin 4 expression.
AB  - Ginsenoside Rg1 is regarded as one of main bioactive compounds responsible for
      pharmaceutical actions of ginseng with little toxicity and has been shown to have
      possibly neuroprotective effects. However, the mechanism of its neuroprotection
      for acute ischemic stroke is still elusive. The purpose of present study is thus
      to assess the neuroprotective effects of the ginsenoside Rg1 against blood brain
      barrier disruption and neurological injury in a rat model of cerebral
      ischemia/reperfusion, and then to explore the mechanisms for these
      neuroprotective effects by targeting aquaporin 4. Focal cerebral ischemia was
      induced by middle cerebral artery occlusion. Neurological examinations were
      performed by using Longa's 5-point scale. Evans blue dye was used to investigate
      the effects of ginsenoside Rg1 on blood brain barrier permeability.
      Immunohistochemical analysis and real-time fluorescence quantitative polymerase
      chain reaction were used to assess aquaporin 4 expression. As a result, general
      linear model with repeated measures analysis of variance for neurological scores
      at 5 repeated measures showed that ginsenoside Rg1-treated group could
      significantly reduce the changing trend of neurological deficit scores when
      compared with the middle cerebral artery occlusion model group (p<0.05). Compared
      with the middle cerebral artery occlusion model group, ginsenoside Rg1 group has
      significantly decreased Evans blue content and reduced aquaporin 4 expression at
      each time point (p<0.05). In conclusion, ginsenoside Rg1 as a ginsenoside
      neuroprotective agent could improve neurological injury, attenuate blood brain
      barrier disruption and downregulate aquaporin 4 expression induced by cerebral
      ischemia/reperfusion insults in rats. 

PMID- 24462218
TI  - Model approach to estimate the probability of accepting a lot of heterogeneously
      contaminated powdered food using different sampling strategies.
AB  - Current sampling plans assume a random distribution of microorganisms in food.
      However, food-borne pathogens are estimated to be heterogeneously distributed in
      powdered foods. This spatial distribution together with very low level of
      contaminations raises concern of the efficiency of current sampling plans for the
      detection of food-borne pathogens like Cronobacter and Salmonella in powdered
      foods such as powdered infant formula or powdered eggs. An alternative approach
      based on a Poisson distribution of the contaminated part of the lot (Habraken
      approach) was used in order to evaluate the probability of falsely accepting a
      contaminated lot of powdered food when different sampling strategies were
      simulated considering variables such as lot size, sample size, microbial
      concentration in the contaminated part of the lot and proportion of contaminated
      lot. The simulated results suggest that a sample size of 100g or more corresponds
      to the lower number of samples to be tested in comparison with sample sizes of 10
      or 1g. Moreover, the number of samples to be tested greatly decrease if the
      microbial concentration is 1CFU/g instead of 0.1CFU/g or if the proportion of
      contamination is 0.05 instead of 0.01. Mean contaminations higher than 1CFU/g or
      proportions higher than 0.05 did not impact on the number of samples. The
      Habraken approach represents a useful tool for risk management in order to design
      a fit-for-purpose sampling plan for the detection of low levels of food-borne
      pathogens in heterogeneously contaminated powdered food. However, it must be
      outlined that although effective in detecting pathogens, these sampling plans are
      difficult to be applied since the huge number of samples that needs to be tested.
      Sampling does not seem an effective measure to control pathogens in powdered
      food. 

PMID- 24462217
TI  - Widespread RNA metabolism impairment in sporadic inclusion body myositis TDP43
      proteinopathy.
AB  - TDP43 protein mislocalization is a hallmark of the neurodegenerative diseases
      amyotrophic lateral sclerosis and frontotemporal dementia, and mutations in the
      gene encoding TDP43 cause both disorders, further highlighting its role in
      disease pathogenesis. TDP43 is a heterogenous ribonucleoprotein, therefore
      suggesting that alterations in RNA metabolism play a role in these disorders,
      although direct evidence in patients is lacking. Sporadic inclusion body myositis
      (sIBM) is the most common acquired myopathy occurring in adults aged older than
      50 years and abnormal cytoplasmic accumulations of TDP43 have been consistently
      described in sIBM myofibers. Here, we exploit high quality RNA from frozen sIBM
      muscle biopsies for transcriptomic studies on TDP43-proteinopathy patient tissue.
      Surprisingly, we found widespread sIBM-specific changes in the RNA metabolism
      pathways themselves. Consistent with this finding, we describe novel RNA binding
      proteins to mislocalize in the cytoplasm of sIBM myofibers and splicing changes
      in MAPT, a gene previously shown to play a role in sIBM. Our data indicate
      widespread alterations of RNA metabolism are a novel aspect of disease
      pathogenesis in sIBM. These findings also document an association, in TDP43
      proteinopathy patients, between heterogenous ribonucleoprotein pathology and RNA
      metabolism alterations and carry importance for neurodegenerative diseases, such
      as amyotrophic lateral sclerosis and frontotemporal dementia.

PMID- 24462219
TI  - The effect of probe inaccuracies on the quantitative model-based analysis of high
      angle annular dark field scanning transmission electron microscopy images.
AB  - Quantitative structural and chemical information can be obtained from high angle
      annular dark field scanning transmission electron microscopy (HAADF STEM) images
      when using statistical parameter estimation theory. In this approach, we assume
      an empirical parameterized imaging model for which the total scattered
      intensities of the atomic columns are estimated. These intensities can be related
      to the material structure or composition. Since the experimental probe profile is
      assumed to be known in the description of the imaging model, we will explore how
      the uncertainties in the probe profile affect the estimation of the total
      scattered intensities. Using multislice image simulations, we analyze this effect
      for Cs corrected and non-Cs corrected microscopes as a function of inaccuracies
      in cylindrically symmetric aberrations, such as defocus and spherical aberration
      of third and fifth order, and non-cylindrically symmetric aberrations, such as 2
      fold and 3-fold astigmatism and coma. 

PMID- 24462220
TI  - Deriving costs of service use among an urban homeless population.
AB  - The purpose of this study was to describe a novel approach to calculating service
      use costs across multiple domains of service for homeless populations. A randomly
      selected sample of homeless persons was interviewed in St. Louis, MO and followed
      for 2 years. Service- and cost-related data were collected from homeless
      individuals and from the agencies serving them. Detailed interviews of study
      participants and of agency personnel in specific domains of service (medical,
      psychiatric, substance abuse, homeless maintenance, and homeless amelioration
      services) were conducted using a standardized approach. Service utilization data
      were obtained from agency records. Standardized service-related costs were
      derived and aggregated across multiple domains from agency-reported data. Housing
      status was not found to be significantly associated with costs. Although labor
      intensive, this approach to cost estimation allows costs to be accurately
      compared across domains. These methods could potentially be applied to other
      populations. 

PMID- 24462222
TI  - The relationship between pregnancy intention and alcohol use behavior: an
      analysis of PRAMS data.
AB  - This study examined the relationship between pregnancy intention and change in
      perinatal alcohol use between 3 months prior to pregnancy and the last 3 months
      of pregnancy from a large national sample of women in the United States, the 2004
      2008 Pregnancy Risk Assessment Monitoring System (PRAMS). The study sample
      consisted of 95,728 women who reported any alcohol drinking in 3 months prior to
      pregnancy. There was no relationship between pregnancy intention and cessation or
      reduction in alcohol use. Those whose pregnancies were unwanted were
      significantly more likely to report binge drinking during pregnancy compared to
      women with intended/mistimed pregnancies (AOR 1.55 [95% CI: 1.20, 1.99]). These
      findings suggest that interventions targeting binge drinking, perhaps
      particularly among women who drink in the 3 months prior to pregnancy and who do
      not want to become pregnant, are needed.

PMID- 24462221
TI  - Does age at first treatment episode make a difference in outcomes over 11 years?
AB  - This study examines the associations between age at first substance use treatment
      entry and trajectory of outcomes over 11 years. We found significant differences
      in individual and treatment characteristics between adult intakes first treated
      during young adulthood (25 years or younger) and those first treated at an older
      age. Compared to their first treated older age counterparts matched on
      demographics and dependence type, those who entered first treatment during young
      adulthood had on average an earlier onset for substance use but a shorter
      duration between first substance use and first treatment entry; they also had
      worse alcohol and other drug outcomes 11 years post treatment entry. While
      subsequent substance use treatment and 12-step meeting attendance are important
      for both age groups in maintaining positive outcomes, relationships varied by age
      group. Findings underline the importance of different continuing care management
      strategies for those entering first treatment at different developmental stages.

PMID- 24462223
TI  - The moderating role of social networks in the relationship between alcohol
      consumption and treatment utilization for alcohol-related problems.
AB  - Many individuals wait until alcohol use becomes severe before treatment is
      sought. However, social networks, or the number of social groups an individual
      belongs to, may play a moderating role in this relationship. Logistic regression
      examined the interaction of alcohol consumption and social networks as a
      predictor of treatment utilization while adjusting for sociodemographic and
      clinical variables among 1,433 lifetime alcohol-dependent respondents from wave 2
      of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC).
      Results showed that social networks moderate the relationship between alcohol
      consumption and treatment utilization such that for individuals with few network
      ties, the relationship between alcohol consumption and treatment utilization was
      diminished, compared to the relationship between alcohol consumption and
      treatment utilization for individuals with many network ties. Findings offer
      insight into how social networks, at times, can influence individuals to pursue
      treatment, while at other times, influence individuals to stay out of treatment,
      or seek treatment substitutes. 

PMID- 24462224
TI  - Serum 25-hydroxyvitamin D level as an independent determinant of quality of life
      in osteoporosis with a high risk for fracture.
AB  - BACKGROUND: Deteriorated quality of life (QOL) is a major problem in osteoporotic
      women. However, little is known regarding the determinants of QOL in patients
      with osteoporosis. OBJECTIVE: Our aim was to explore the role of vitamin D status
      on QOL score in osteoporosis with high fracture risk. METHODS: Patients were
      osteoporotic women aged >=70 years and with >=1 risk factor for incident
      fracture, namely prevalent osteoporotic fracture, bone mineral density (BMD) >
      3.0 SD of young adult mean, or high bone turnover marker. Health-related QOL was
      assessed using the Japanese Osteoporosis Quality of Life Questionnaire (JOQOL).
      When patients were classified into quartiles by total QOL score). Serum 25
      hydroxyvitamin D (25[OH]D) level was measured by immunoassay. RESULTS: A total of
      1585 osteoporotic women were included in the study (age range, 70-95 years). Age,
      body mass index, serum 25(OH)D status (low, normal, or high), bone mineral
      density, number of prevalent vertebral fractures, presence of hypertension,
      presence of osteoarthritis, and history of falls were significantly correlated
      with QOL quartile. Multivariate liner regression analysis indicated that low
      serum 25(OH)D level (<20 ng/mL) was an independent determinant of total QOL score
      quartile (P = 0.0055). The conventional determinants of QOL-age (P < 0.0001),
      body mass index (P = 0.0060), number of prevalent vertebral fractures (P <
      0.0001), presence of osteoarthritis (P = 0.0074), and history of fall (P =
      0.0098)-were also independent determinants of total QOL score. CONCLUSIONS: These
      results strongly suggest that low serum 25(OH)D level was a significant
      determinant of QOL in these osteoporotic women, independently of the conventional
      factors that reduce QOL. Maintenance of serum 25(OH)D levels >20 ng/mL may be
      required to maintain patients' QOL in osteoporosis.

PMID- 24462225
TI  - Perineal reconstruction: From lotus petal to "canopy". An alternative to the
      standard surgical algorithm.

PMID- 24462226
TI  - Response to: 'A novel method for the harvest of a large full thickness skin graft
      using a quiver'.

PMID- 24462227
TI  - An unusual referral with skin loss following intermittent pneumatic compression
      therapy.

PMID- 24462228
TI  - Altered polysomnographic profile in juvenile myoclonic epilepsy.
AB  - PURPOSE: To study the spectra of sleep profile using PSG in a cohort of patients
      with JME attending a University hospital. METHODOLOGY: This prospective cross
      sectional case-control study involved 25 patients of JME (age: 22.0+/-6.3 years;
      M:F=13:12) on valproic acid (VPA) and 25 matched healthy controls (age: 23.2+/
      3.04 years; M:F=16:9) were recruited. All patients underwent clinical assessment,
      electroencephalogram (EEG), and evaluation with sleep questionnaire and PSG.
      RESULTS: PSG analysis revealed significant alterations in sleep architecture in
      the JME group in the form of reduced mean sleep efficiency (p=<0.035) and number
      of patients with reduced sleep efficiency (p=0.001), increased mean sleep onset
      latency (p=0.04) and number of patients with increased sleep latency (p=0.023),
      reduced mean N2 sleep percentage (p=0.005) and reduced mean total NREM (non-rapid
      eye movement) sleep (p=0.001) and increased mean wake percentage (p=0.001). The
      frequency of arousals, involuntary limb movements, and event related arousals in
      the JME groups was not different from the controls. Patients >20 years had
      reduced total sleep time compared to those <20 years (p=0.012). Patients with
      seizures for >5 years had reduced NREM sleep percentage (p=0.042) and those on
      VPA therapy >1 year had a longer stage 2 (p=0.03) and N3 latency (p=0.03).
      Patients on <=600mg/day of VPA had a higher prevalence of isolated limb movements
      (p=0.01). CONCLUSIONS: PSG revealed significant alterations in sleep architecture
      in JME despite adequate seizure control. There was variable degree of PSG
      phenotypic correlation.

PMID- 24462229
TI  - Cognitive-behavioral therapy as continuation treatment to sustain response after
      electroconvulsive therapy in depression: a randomized controlled trial.
AB  - BACKGROUND: Although electroconvulsive therapy (ECT) is the most effective acute
      antidepressant intervention, sustained response rates are low. It has never been
      systematically assessed whether psychotherapy, continuation ECT, or
      antidepressant medication is the most efficacious intervention to maintain
      initial treatment response. METHODS: In a prospective, randomized clinical trial,
      90 inpatients with major depressive disorder (MDD) were treated with right
      unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6
      months guideline-based antidepressant medication (MED) and were randomly assigned
      to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on
      therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm),
      or no add-on therapy (MED-arm). After the 6 months of continuation treatment,
      patients were followed-up for another 6 months. The primary outcome parameter was
      the proportion of patients who remained well after 12 months. RESULTS: Of 90 MDD
      patients starting the acute phase, 70% responded and 47% remitted to acute ECT.
      After 6 months of continuation treatment, significant differences were observed
      in the three treatment arms with sustained response rates of 77% in the CBT-arm,
      40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences
      remained stable with sustained response rates of 65% in the CBT-arm, 28% in the
      ECT-arm, and 33% in the MED-arm. CONCLUSIONS: These results suggest that ultra
      brief pulse ECT as a continuation treatment correlates with low sustained
      response rates. However, the main finding implicates cognitive-behavioral group
      therapy in combination with antidepressants might be an effective continuation
      treatment to sustain response after successful ECT in MDD patients.

PMID- 24462231
TI  - Adaptive control of an active magnetic bearing with external disturbance.
AB  - Adaptive back stepping control (ABC) is originally applied to a linearized model
      of an active magnetic bearing (AMB) system. Our control goal is to regulate the
      deviation of the magnetic bearing from its equilibrium position in the presence
      of an external disturbance and system uncertainties. Two types of ABC methods are
      developed on the AMB system. One is based on full state feedback, for which
      displacement, velocity, and current states are assumed available. The other one
      is adaptive observer based back stepping controller (AOBC) where only
      displacement output is measurable. An observer is designed for AOBC to estimate
      velocity and current states of AMB. Lyapunov approach proves the stabilities of
      both regular ABC and AOBC. Simulation results demonstrate the effectiveness and
      robustness of two controllers. 

PMID- 24462230
TI  - Pretreatment brain states identify likely nonresponse to standard treatments for
      depression.
AB  - BACKGROUND: Treatment approaches for major depressive disorder (MDD) result in
      approximately one third of patients achieving remission after a first treatment.
      Added treatment generally improves remission rates, but approximately one third
      of all patients fail to respond after several treatments (sequential
      monotherapies or combined treatment). A pretreatment biomarker could help
      identify these patients. Overactivity of the subcallosal cingulate has been
      associated with failure of response to treatment in MDD, and it is a potential
      candidate for such a biomarker. METHODS: Investigators enrolled 82 patients with
      MDD currently not receiving treatment in a two-phase treatment study. Patients
      underwent a fluorodeoxyglucose positron emission tomography scan. After scanning,
      patients were randomly assigned to 12 weeks of treatment with either escitalopram
      or cognitive-behavioral therapy (CBT). Patients not achieving remission after 12
      weeks of initial treatment were treated with an additional 12 weeks of
      escitalopram plus CBT. Subcallosal cingulate metabolism was compared between
      patients who failed to achieve a response and patients who achieved remission as
      a result of either phase one or phase two treatment. This analysis was followed
      by a whole-brain analysis making the same comparison. RESULTS: After two phases
      of treatment (24 weeks), 36 patients were identified as remitters, 6 patients
      were responders, and 9 patients were nonresponders. Subcallosal cingulate
      metabolism was significantly higher in nonresponders than remitters. In the
      follow-up whole-brain analysis, increased superior temporal sulcus activity was
      also associated with nonresponse to two treatments. CONCLUSIONS: Patients with
      MDD who fail to achieve remission as a result of CBT or escitalopram, either
      alone or in combination, have a distinct brain metabolic pattern compared with
      patients who achieve remission as a result of CBT, escitalopram, or their
      combination.

PMID- 24462232
TI  - Determination of all feasible robust PID controllers for open-loop unstable plus
      time delay processes with gain margin and phase margin specifications.
AB  - This paper proposes a novel alternative method to graphically compute all
      feasible gain and phase margin specifications-oriented robust PID controllers for
      open-loop unstable plus time delay (OLUPTD) processes. This method is applicable
      to general OLUPTD processes without constraint on system order. To retain
      robustness for OLUPTD processes subject to positive or negative gain variations,
      the downward gain margin (GM(down)), upward gain margin (GM(up)), and phase
      margin (PM) are considered. A virtual gain-phase margin tester compensator is
      incorporated to guarantee the concerned system satisfies certain robust safety
      margins. In addition, the stability equation method and the parameter plane
      method are exploited to portray the stability boundary and the constant gain
      margin (GM) boundary as well as the constant PM boundary. The overlapping region
      of these boundaries is graphically determined and denotes the GM and PM
      specifications-oriented region (GPMSOR). Alternatively, the GPMSOR characterizes
      all feasible robust PID controllers which achieve the pre-specified safety
      margins. In particular, to achieve optimal gain tuning, the controller gains are
      searched within the GPMSOR to minimize the integral of the absolute error (IAE)
      or the integral of the squared error (ISE) performance criterion. Thus, an
      optimal PID controller gain set is successfully found within the GPMSOR and
      guarantees the OLUPTD processes with a pre-specified GM and PM as well as a
      minimum IAE or ISE. Consequently, both robustness and performance can be
      simultaneously assured. Further, the design procedures are summarized as an
      algorithm to help rapidly locate the GPMSOR and search an optimal PID gain set.
      Finally, three highly cited examples are provided to illustrate the design
      process and to demonstrate the effectiveness of the proposed method.

PMID- 24462233
TI  - Tuning rules for a quick start up in Dynamic Matrix Control.
AB  - This paper pretends to offer design rules for the parameters adjustment of the
      Dynamic Matrix Control (DMC) to allow an easier starting up. The effect on the
      time response of each algorithm parameter that can be tuned by the user is
      studied in an unconstrained system. To this aim, the position of the closed loop
      poles of the equivalent system is calculated. To simplify the study and to obtain
      more direct conclusions the number of poles will be limited using a First Order
      Plus Death Time simplification of the real plant. Design rules proposed in this
      study are tested in some simulated benchmarks and in a real plant. 

PMID- 24462234
TI  - The effect of hyperactive bladder severity on healthcare utilization and labor
      productivity.
AB  - OBJECTIVE: To explore the relationship between the severity of urinary urge
      incontinence (UUI) on healthcare resources utilization (HRU) and loss of labor
      productivity of subjects with overactive bladder (OAB) in the general population
      in Spain. METHODS: Secondary analysis of a cross-sectional web-based study
      conducted in the general population >18 years, through a battery of HRU questions
      asked using an online method. Probable OAB subjects were identified using a
      previously validated algorithm and a score >8 in the OAB-V8 questionnaire. HRU
      questions included an assessment of concomitant medication used as a consequence
      of OAB/UUI, pad utilization, and medical office visits. Patients were grouped
      according to the number of UUI episodes into 0, 1, 2-3 or 4+ episodes. RESULTS:
      Of a total of 2,035 subjects participating from the general population, 396
      patients [52.5% women, mean age: 55.3 (11.1) years, OAB-V8 mean score: 14.5
      (7.9)] were analyzed; 203 (51.3%) with 0 episodes, 119 (30.1%) with 1, 52 (13.1%)
      with 2 or 3, and 22 (5.6%) with 4 or more episodes. A linear and significant
      adjusted association was observed between the number of UUI episodes and HRU; the
      higher the number of daily episodes the higher the HRU. Subjects with more
      episodes had medical visits more frequently at the primary care (P = .001) and
      specialist (P = .009) level as well. Consumption of day (P < .001) and night (P <
      .001) urinary absorbents, anxiolytic medicines (P = .021) and antibiotics (P =
      .05) was higher in patients with more UUI episodes. CONCLUSION: The severity of
      OAB in terms of frequency of daily urge incontinence episodes was significantly
      and linearly associated with higher healthcare resources utilization and a
      decrease in labor productivity in subjects with probable OAB in Spain.

PMID- 24462235
TI  - Growth, nutrient status, and photosynthetic response to diesel-contaminated soil
      of a cordgrass, Spartina argentinensis.
AB  - The present study was conduced to investigate the tolerance limits of Spartina
      argentinensis, which occurs in inland marshes of the Chaco-Pampean regions of
      Argentina, to diesel-contaminated soil. A glasshouse experiment was designed to
      investigate the effect of diesel fuel from 0% to 3% on growth and photosynthetic
      apparatus of S. densiflora by measuring gas exchange and photosynthetic pigments.
      We also performed chemical analysis of plant samples, and determined mycorrhizal
      index. Tiller and root biomasses declined with increasing diesel fuel
      concentration, as well as photosynthetic rate (A). Reductions in A could be
      accounted for by non-stomatal limitations. Mycorrhizal roots of S. argentinensis
      were reduced by the presence of diesel fuel, but did not affect its nutritional
      status; in fact, most element concentrations increased with diesel contamination.
      Despite the negative effect of diesel-contaminated soil, S. argentinensis
      continued growing, which could be useful management options for phytorremediation
      of diesel-contaminated soils. 

PMID- 24462236
TI  - Polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in the equatorial
      Indian Ocean: temporal trend, continental outflow and air-water exchange.
AB  - Nineteen pairs of air and seawater samples collected from the equatorial Indian
      Ocean onboard the Shiyan I from 4/2011 to 5/2011 were analyzed for PCBs and HCB.
      Gaseous concentrations of ?(ICES)PCBs (ICES: International Council for the
      Exploration of the Seas) and HCB were lower than previous data over the study
      area. Air samples collected near the coast had higher levels of PCBs relative to
      those collected in the open ocean, which may be influenced by proximity to source
      regions and air mass origins. Dissolved concentrations of ?(ICES)PCBs and HCB
      were 1.4-14 pg L-1 and 0.94-13 pg L-1, with the highest concentrations in the
      sample collected from Strait of Malacca. Fugacity fractions suggest
      volatilization of PCBs and HCB from the seawater to air during the cruise, with
      fluxes of 0.45-34 ng m-2 d-1 and 0.36-18 ng m-2 d-1, respectively.

PMID- 24462237
TI  - A probabilistic model for accidental cargo oil outflow from product tankers in a
      ship-ship collision.
AB  - In risk assessment of maritime transportation, estimation of accidental oil
      outflow from tankers is important for assessing environmental impacts. However,
      there typically is limited data concerning the specific structural design and
      tank arrangement of ships operating in a given area. Moreover, there is
      uncertainty about the accident scenarios potentially emerging from ship
      encounters. This paper proposes a Bayesian network (BN) model for reasoning under
      uncertainty for the assessment of accidental cargo oil outflow in a ship-ship
      collision where a product tanker is struck. The BN combines a model linking
      impact scenarios to damage extent with a model for estimating the tank layouts
      based on limited information regarding the ship. The methodology for constructing
      the model is presented and output for two accident scenarios is shown. The
      discussion elaborates on the issue of model validation, both in terms of the BN
      and in light of the adopted uncertainty/bias-based risk perspective. 

PMID- 24462238
TI  - Effect of change in systolic blood pressure between clinic visits on estimated 10
      year cardiovascular disease risk.
AB  - Systolic blood pressure (SBP) often varies between clinic visits within
      individuals, which can affect estimation of cardiovascular disease (CVD) risk. We
      analyzed data from participants with two clinic visits separated by a median of
      17 days in the Third National Health and Nutrition Examination Survey (n = 808).
      Ten-year CVD risk was calculated with SBP obtained at each visit using the Pooled
      Cohort Equations. The mean age of participants was 46.1 years, and 47.3% were
      male. The median SBP difference between the two visits was -1 mm Hg (1st to 99th
      percentiles: -23 to 32 mm Hg). The median estimated 10-year CVD risk was 2.5% and
      2.4% at the first and second visit, respectively (1st to 99th percentiles -5.2%
      to +7.1%). Meaningful risk reclassification (ie, across the guideline recommended
      7.5% threshold for statin initiation) occurred in 12 (11.3%) of 106 participants
      whose estimated CVD risk was between 5% and 10%, but only in two (0.3%) of 702
      participants who had a 10-year estimated CVD risk of <5% or >10%. SBP variability
      can affect CVD risk estimation, and can influence statin eligibility for
      individuals with an estimated 10-year CVD risk between 5% and 10%. 

PMID- 24462239
TI  - A new encephalitis with GABAA receptor antibodies.

PMID- 24462240
TI  - Encephalitis with refractory seizures, status epilepticus, and antibodies to the
      GABAA receptor: a case series, characterisation of the antigen, and analysis of
      the effects of antibodies.
AB  - BACKGROUND: Increasing evidence suggests that seizures and status epilepticus can
      be immune-mediated. We aimed to describe the clinical features of a new epileptic
      disorder, and to establish the target antigen and the effects of patients'
      antibodies on neuronal cultures. METHODS: In this observational study, we
      selected serum and CSF samples for antigen characterisation from 140 patients
      with encephalitis, seizures or status epilepticus, and antibodies to unknown
      neuropil antigens. The samples were obtained from worldwide referrals of patients
      with disorders suspected to be autoimmune between April 28, 2006, and April 25,
      2013. We used samples from 75 healthy individuals and 416 patients with a range
      of neurological diseases as controls. We assessed the samples using
      immunoprecipitation, mass spectrometry, cell-based assay, and analysis of
      antibody effects in cultured rat hippocampal neurons with confocal microscopy.
      FINDINGS: Neuronal cell-membrane immunoprecipitation with serum of two index
      patients revealed GABAA receptor sequences. Cell-based assay with HEK293
      expressing alpha1/beta3 subunits of the GABAA receptor showed high titre serum
      antibodies (>1:160) and CSF antibodies in six patients. All six patients (age 3
      63 years, median 22 years; five male patients) developed refractory status
      epilepticus or epilepsia partialis continua along with extensive cortical
      subcortical MRI abnormalities; four patients needed pharmacologically induced
      coma. 12 of 416 control patients with other diseases, but none of the healthy
      controls, had low-titre GABAA receptor antibodies detectable in only serum
      samples, five of them also had GAD-65 antibodies. These 12 patients (age 2-74
      years, median 26.5 years; seven male patients) developed a broader spectrum of
      symptoms probably indicative of coexisting autoimmune disorders: six had
      encephalitis with seizures (one with status epilepticus needing pharmacologically
      induced coma; one with epilepsia partialis continua), four had stiff-person
      syndrome (one with seizures and limbic involvement), and two had opsoclonus
      myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were
      assessable had full (three patients) or partial (nine patients) response to
      immunotherapy or symptomatic treatment, and three died. Patients' antibodies
      caused a selective reduction of GABAA receptor clusters at synapses, but not
      along dendrites, without altering NMDA receptors and gephyrin (a protein that
      anchors the GABAA receptor). INTERPRETATION: High titres of serum and CSF GABAA
      receptor antibodies are associated with a severe form of encephalitis with
      seizures, refractory status epilepticus, or both. The antibodies cause a
      selective reduction of synaptic GABAA receptors. The disorder often occurs with
      GABAergic and other coexisting autoimmune disorders and is potentially treatable.
      FUNDING: The National Institutes of Health, the McKnight Neuroscience of Brain
      Disorders, the Fondo de Investigaciones Sanitarias, Fundacio la Marato de TV3,
      the Netherlands Organisation for Scientific Research (Veni-incentive), the Dutch
      Epilepsy Foundation.

PMID- 24462241
TI  - Education and counseling in the methadone treatment setting improves knowledge of
      viral hepatitis.
AB  - The aim of this study was to evaluate the effectiveness of an educational method
      of providing viral hepatitis education for methadone maintenance patients. Four
      hundred forty participants were randomly assigned to either a control or a
      motivationally-enhanced viral hepatitis education and counseling intervention.
      Viral hepatitis A (HAV), B (HBV), and C (HCV) knowledge tests were administered
      at baseline, following each of two education sessions (post-education), and at a
      3-month follow-up assessment. Results indicated a significant increase in
      knowledge of HAV, HBV, and HCV over time. No differences were found in knowledge
      between the intervention groups in knowledge acquisition regarding any of the
      hepatitis viruses suggesting that a motivational interviewing style may not
      augment hepatitis knowledge beyond standard counseling. A two-session viral
      hepatitis education intervention effectively promotes hepatitis knowledge and can
      be integrated in methadone treatment settings. 

PMID- 24462243
TI  - Latent practice profiles of substance abuse treatment counselors: do evidence
      based techniques displace traditional techniques?
AB  - As more substance abuse treatment counselors begin to use evidence-based
      treatment techniques, questions arise regarding the continued use of traditional
      techniques. This study aims to (1) assess whether there are meaningful practice
      profiles among practitioners reflecting distinct combinations of cognitive
      behavioral and traditional treatment techniques; and (2) if so, identify
      practitioner characteristics associated with the distinct practice profiles.
      Survey data from 278 frontline counselors working in community substance abuse
      treatment organizations were used to conduct latent profile analysis. The
      emergent practice profiles illustrate that practitioners vary most in the use of
      traditional techniques. Multinomial regression models suggest that practitioners
      with less experience, more education, and less traditional beliefs about
      treatment and substance abuse are least likely to mix traditional techniques with
      cognitive-behavioral techniques. Findings add to the understanding of how
      evidence-based practices are implemented in routine settings and have
      implications for training and support of substance abuse treatment counselors. 

PMID- 24462242
TI  - Disseminating contingency management: impacts of staff training and
      implementation at an opiate treatment program.
AB  - Guided by a comprehensive implementation model, this study examined
      training/implementation processes for a tailored contingency management (CM)
      intervention instituted at a Clinical Trials Network-affiliate opioid treatment
      program (OTP). Staff-level training outcomes (intervention delivery skill,
      knowledge, and adoption readiness) were assessed before and after a 16-hour
      training, and again following a 90-day trial implementation period. Management
      level implementation outcomes (intervention cost, feasibility, and
      sustainability) were assessed at study conclusion in a qualitative interview with
      OTP management. Intervention effectiveness was also assessed via independent
      chart review of trial CM implementation vs. a historical control period. Results
      included: 1) robust, durable increases in delivery skill, knowledge, and adoption
      readiness among trained staff; 2) positive managerial perspectives of
      intervention cost, feasibility, and sustainability; and 3) significant clinical
      impacts on targeted patient indices. Collective results offer support for the
      study's collaborative intervention design and the applied, skills-based focus of
      staff training processes. Implications for CM dissemination are discussed. 

PMID- 24462244
TI  - From counselor skill to decreased marijuana use: does change talk matter?
AB  - Client language about change, or change talk, is hypothesized to mediate the
      relationship between counselor fidelity in motivational interviewing (MI) and
      drug use outcomes. To investigate this causal chain, this study used data from an
      MI booster delivered to alternative high school students immediately after a
      universal classroom-based drug abuse prevention program. One hundred and seventy
      audio-recorded MI sessions about substance use were coded using the motivational
      interviewing skill code 2.5. Structural equation modeling showed that percentage
      of change talk on the part of the client mediated three of the four relationships
      between MI quality indicators and marijuana outcomes, while percentage of
      reflections of change talk showed a main effect of counselor skill on marijuana
      outcomes. Findings support change talk as an active ingredient of MI and provide
      new empirical support for the micro-skills of MI. 

PMID- 24462245
TI  - The psychometric development and initial validation of the DCI-A short form for
      adolescent therapeutic community treatment process.
AB  - The 5-factor client-report Dimensions of Change in Therapeutic Communities
      Treatment Instrument-Adolescent (DCI-A) was developed to assess adolescent
      substance abuse treatment process in the therapeutic community (TC). The goal of
      this study was to use bifactor modeling to derive a unidimensional DCI-A short
      form (DCI-A-SF) that would represent content from the original DCI-A factors.
      Data are from 442 adolescents receiving treatment at one of seven residential TC
      programs. Bifactor analyses suggested selection of seven DCI-A items to comprise
      the short form. Three items are from the treatment motivation factor, and one
      item was selected from each of the remaining four factors. Confirmatory factor
      analysis suggested that the 7-item DCI-A-SF is strongly unidimensional, and
      unidimensional IRT analysis of the items indicated good internal consistency. A
      structural equation model that demonstrates the mediating relationship of DCI-A
      SF with other measures, including demographic and pre-treatment characteristics,
      and subsequent treatment completion, provides preliminary evidence of internal
      validity. 

PMID- 24462246
TI  - Examining the performance of the brief addiction monitor.
AB  - The Center for Excellence in Drug Abuse Treatment and Education (Center for
      Excellence in Substance Abuse Treatment and Education (CESATE; 2010). Brief
      Addiction Monitor: Manual of Operations. Philadelphia, PA) recently suggested
      that Veterans Affairs' (VA) addictions treatment programs, in order to encourage
      measurement based care, begin using a new measure of substance abuse, the Brief
      Addictions Monitor (BAM). To date, only one study Caccolia et al, 2013.
      Development and initial evaluation of the Brief Addiction Monitor (BAM). Journal
      of Substance Abuse Treatment, 44, 256-63. doi:
      http://dx.doi.org/10.1016/j.jsat.2012.07.013) has examined the psychometric
      properties of a version of this instrument. However, this study did not use the
      version of the BAM currently available to most VA providers via the mental health
      assistant software; rather, the authors reported the properties of a BAM where
      most of the items had continuous (or near continuous) response options. The
      current study seeks to provide data on the version of the BAM which uses 5 point
      Likert scale response options for its questions, the version available on the
      mental health assistant software. Based on data from more than 700 veterans
      enrolled in out-patient (OP) and in-patient (IP) addictions treatment programs,
      this study examined the factor structure, reliability, and validity of this
      version of the BAM. Across both groups, results suggested that the BAM lacked a
      reliable factor structure, in contrast to the findings from the earlier study.
      However, a single scale, composed of a minority of items on the BAM, showed
      promise. A minority of the items (five) provided valid information across both OP
      and IP samples when applied individually, as indicated by convergent and
      divergent validity comparisons with other measures of functioning; tracking
      changes in functioning over the course of treatment; and correlating with changes
      in convergent and divergent validity measures. This partially supported the
      CESATE (CESATE; 2010). Brief Addiction Monitor: Manual of Operations.
      Philadelphia, PA) call to use the individual BAM items. Overall, results
      suggested that changing the structure of the response options may have had a
      negative impact on the psychometric properties of the BAM. 

PMID- 24462247
TI  - Dividing cells regulate their lipid composition and localization.
AB  - Although massive membrane rearrangements occur during cell division, little is
      known about specific roles that lipids might play in this process. We report that
      the lipidome changes with the cell cycle. LC-MS-based lipid profiling shows that
      11 lipids with specific chemical structures accumulate in dividing cells. Using
      AFM, we demonstrate differences in the mechanical properties of live dividing
      cells and their isolated lipids relative to nondividing cells. In parallel,
      systematic RNAi knockdown of lipid biosynthetic enzymes identified enzymes
      required for division, which highly correlated with lipids accumulated in
      dividing cells. We show that cells specifically regulate the localization of
      lipids to midbodies, membrane-based structures where cleavage occurs. We conclude
      that cells actively regulate and modulate their lipid composition and
      localization during division, with both signaling and structural roles likely.
      This work has broader implications for the active and sustained participation of
      lipids in basic biology. 

PMID- 24462249
TI  - Radically different thioredoxin domain arrangement of ERp46, an efficient
      disulfide bond introducer of the mammalian PDI family.
AB  - The mammalian endoplasmic reticulum (ER) contains a diverse oxidative protein
      folding network in which ERp46, a member of the protein disulfide isomerase (PDI)
      family, serves as an efficient disulfide bond introducer together with
      Peroxiredoxin-4 (Prx4). We revealed a radically different molecular architecture
      of ERp46, in which the N-terminal two thioredoxin (Trx) domains with positively
      charged patches near their peptide-binding site and the C-terminal Trx are linked
      by unusually long loops and arranged extendedly, forming an opened V-shape.
      Whereas PDI catalyzes native disulfide bond formation by the cooperative action
      of two mutually facing redox-active sites on folding intermediates bound to the
      central cleft, ERp46 Trx domains are separated, act independently, and engage in
      rapid but promiscuous disulfide bond formation during early oxidative protein
      folding. Thus, multiple PDI family members likely contribute to different stages
      of oxidative folding and work cooperatively to ensure the efficient production of
      multi-disulfide proteins in the ER. 

PMID- 24462248
TI  - Neonatal insulin action impairs hypothalamic neurocircuit formation in response
      to maternal high-fat feeding.
AB  - Maternal metabolic homeostasis exerts long-term effects on the offspring's health
      outcomes. Here, we demonstrate that maternal high-fat diet (HFD) feeding during
      lactation predisposes the offspring for obesity and impaired glucose homeostasis
      in mice, which is associated with an impairment of the hypothalamic melanocortin
      circuitry. Whereas the number and neuropeptide expression of anorexigenic
      proopiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP) neurons,
      electrophysiological properties of POMC neurons, and posttranslational processing
      of POMC remain unaffected in response to maternal HFD feeding during lactation,
      the formation of POMC and AgRP projections to hypothalamic target sites is
      severely impaired. Abrogating insulin action in POMC neurons of the offspring
      prevents altered POMC projections to the preautonomic paraventricular nucleus of
      the hypothalamus (PVH), pancreatic parasympathetic innervation, and impaired
      glucose-stimulated insulin secretion in response to maternal overnutrition. These
      experiments reveal a critical timing, when altered maternal metabolism disrupts
      metabolic homeostasis in the offspring via impairing neuronal projections, and
      show that abnormal insulin signaling contributes to this effect. 

PMID- 24462250
TI  - Conformational changes induced by the A21G Flemish mutation in the amyloid
      precursor protein lead to increased Abeta production.
AB  - Proteolysis of the beta C-terminal fragment (beta-CTF) of the amyloid precursor
      protein generates the Abeta peptides associated with Alzheimer's disease.
      Familial mutations in the beta-CTF, such as the A21G Flemish mutation, can
      increase Abeta secretion. We establish how the Flemish mutation alters the
      structure of C55, the first 55 residues of the beta-CTF, using FTIR and solid
      state NMR spectroscopy. We show that the A21G mutation reduces beta sheet
      structure of C55 from Leu17 to Ala21, an inhibitory region near the site of the
      mutation, and increases alpha-helical structure from Gly25 to Gly29, in a region
      near the membrane surface and thought to interact with cholesterol. Cholesterol
      also increases Abeta peptide secretion, and we show that the incorporation of
      cholesterol into model membranes enhances the structural changes induced by the
      Flemish mutant, suggesting a common link between familial mutations and the
      cellular environment. 

PMID- 24462251
TI  - Interaction of Fapp1 with Arf1 and PI4P at a membrane surface: an example of
      coincidence detection.
AB  - Interactions among ADP-ribosylation factors (ARFs), various adaptor proteins, and
      membrane lipids are essential for intracellular vesicle transport of a variety of
      cellular materials. Here, we present nuclear magnetic resonance (NMR)-based
      information on the nature of the interaction of yeast Arf1 (yArf1) and the
      pleckstrin homology (PH) domain of four-phosphate-adaptor protein 1 (Fapp1) as it
      occurs at a model membrane surface. Interactions favor a model in which Fapp1 is
      partially embedded in the membrane and interacts with a membrane-associated Arf1
      molecule primarily through contacts between residues in switch I of Arf1 and
      regions near and under the solution exposed C-terminal extension of the PH
      domain. The Arf1 binding site on Fapp1-PH is distinct from a positively charged
      phosphatidylinositol-4-phosphate (PI4P) binding site. A structural model is
      constructed that supports coincidence detection of both activated ARF and PI4P as
      a mechanism facilitating Fapp1 recruitment to membranes.

PMID- 24462252
TI  - [Isolated pelvic recurrences of cervical carcinoma treated with salvage
      chemoradiotherapy].
AB  - PURPOSE: Evaluation of the results of salvage radiation therapy with curative
      intent in the treatment of recurrent cervical carcinoma. PATIENTS AND METHODS:
      Fourteen patients with a recurrence of a cervical cancer were treated in our
      department between 1982 and 2009. Five patients had a pelvic relapse, four a
      vaginal relapse and five a pelvic lymph node relapse. Four patients had first a
      surgical resection of the relapse, which was incomplete in two patients. All
      patients had pelvic radiotherapy with a median dose of 55Gy in conventional
      fractionation. Concurrent chemotherapy was administered to 12 patients. A vaginal
      brachytherapy with a median dose of 20Gy was performed in addition in 3 patients.
      The median follow-up was 39months. RESULTS: Safety of radiation therapy was
      correct with 29% of grade 3 acute or intestinal toxicity. Tumor control was
      observed in 10 patients (71%). Four patients presented a locoregional tumor
      progression. At the time of analysis, three patients had died from their cancer.
      From the date of relapse, the rate of overall survival at 2 and 5year was
      respectively 84% and 74%. Three patients (21%) had severe late effects.
      CONCLUSION: In our experience, chemoradiotherapy can achieve a high rate of
      remission in patients with isolated pelvic recurrence of cervical cancer. This
      treatment is feasible only if the patient had not received radiation therapy
      before or if the relapse is out of the previously irradiated volume.

PMID- 24462253
TI  - A high resolution melting real time PCR for mapping of filaria infection in
      domestic cats living in brugian filariosis-endemic areas.
AB  - We present here a real time PCR with high resolution melting (HRM) analysis for
      determining the prevalence and distribution of filarial species in domestic cats
      residing in brugian filariosis endemic areas of Narathiwat province, Thailand.
      Filarial species can be clearly distinguished in a single well using a single
      pair of primers. Blood samples were taken from a total of 2039 domestic cats
      living in endemic areas. Microfilariae were detected in 5.7% of the sample, while
      the overall prevalence of filaria infection by HRM analysis was 6.6%. The
      filariae species found in the infected cats were Brugia malayi, Dirofilaria
      immitis, D. repens as well as Acanthocheilonema (Dipetalonema) reconditum. This
      is the first report of A. reconditum infection from Thailand. The study also
      observed an overlapping of the distribution areas of animal and human filariae.
      From a public health perspective, the distribution and prevalence of these
      nematodes warrant an appropriate drug-based prophylaxis to be administered to
      cats in the endemic areas to reduce the number of diseased carriers. Furthermore,
      this molecular approach is more sensitive than microfilariae detection, enables
      species identification and greatly facilitates the collection of epidemiological
      data. Thus, the present study may help to bridge human-animal interface by
      coordinating research outcomes with the control of zoonoses that is vitally
      important for human and veterinary public health.

PMID- 24462254
TI  - Male infertility: decreased levels of selenium, zinc and antioxidants.
AB  - In this study, we aimed to compare the level of zinc, selenium, glutathione
      peroxidase activity and antioxidant status in following populations of men:
      severe inflammation in prostate (>10(6) white blood cells in prostate secretion;
      n=29), severe leukocytospermia, (>10(6) white blood cells in semen; n=31), mild
      inflammation, (0.2-1M white blood cells in semen or prostate secretion; n=24),
      non-inflammatory oligozoospermia (n=32) and healthy controls (n=27). Male
      partners of infertile couples had reduced level of antioxidative activity,
      selenium and zinc in their seminal plasma. Most importantly, reduced selenium
      levels were evident in all patient groups regardless of inflammation status.
      Therefore, these patients might gain some benefit from selenium supplementation. 

PMID- 24462255
TI  - Discussion.

PMID- 24462256
TI  - Current treatment of renal artery aneurysms may be too aggressive.
AB  - OBJECTIVE: Most studies recommend repair of renal artery aneurysms (RAAs) >2 cm
      in diameter in asymptomatic patients, but other studies have suggested that their
      natural history may be more benign. We hypothesized that rupture and death in
      patients with asymptomatic RAAs is low and that current recommendations for RAA
      treatment at 2 cm may be too aggressive. METHODS: Retrospective review of all
      RAAs treated at a tertiary care medical center from 2002 to 2012. RESULTS: Fifty
      nine RAA were identified in 40 patients (mean age at diagnosis, 56 years;
      male:female ratio, 17:23); 31 were saccular, 8 were fusiform, and 5 were bilobed.
      Twenty-nine patients were asymptomatic; the remainder of patients presented with
      hematuria (n = 4), abdominal pain (n = 3), difficult-to-control hypertension (n =
      3), or flank pain (n = 2). Aneurysm location included the main renal artery
      bifurcation (n = 35), main trunk (n = 7), primary branch (n = 6), pole artery (n
      = 6), and secondary branch (n = 1). Operative management of RAAs included vein
      patch (n = 6), prosthetic patch (n = 4), primary repair (n = 3), plication (n =
      1), patch and implantation (n = 1), and ex vivo repair (n = 1). Eight
      asymptomatic RAAs were treated surgically (mean RAA diameter = 2.4 +/- 0.1 cm,
      range, 2-3 cm), with the remaining 33 asymptomatic RAAs being managed
      conservatively (mean RAA diameter = 1.4 +/- 0.1 cm, range, 0.6-2.6 cm). Mean
      hospital length of stay was 4 days, with no late postoperative complications and
      0% mortality. Non-operated patients were followed for a mean of 36 +/- 9 months,
      with no late acute complications and 0% mortality. Mean RAA growth rate of
      patients with multiple imaging studies was 0.60 +/- 0.16 mm/y. CONCLUSIONS: The
      rate of aneurysm rupture and death in our untreated RAA patients is zero, the
      growth rate is 0.60 +/- 0.16 mm/y, and there were no adverse outcomes in
      asymptomatic RAAs >2 cm that were observed. We may currently be too aggressive in
      treating asymptomatic RAAs.

PMID- 24462257
TI  - Stent-assisted coiling of unruptured intracranial aneurysms: long-term follow-up
      in 164 patients with 183 aneurysms.
AB  - PURPOSE: Stent-assisted coiling (SAC) is increasingly used to treat complex
      unruptured intracranial aneurysms (UIA) including wide-necked and fusiform IA.
      However, few data are available over the long-term results of this technique. We
      report our 9-year-experience of SAC of UIA. METHODS: A retrospective review of
      our prospectively maintained database identified all patients treated by SAC for
      an UIA in 2 institutions. The clinical charts, procedural data and angiographic
      results were reviewed. RESULTS: Between 2004 and 2012, we identified 164 patients
      with 183 UIA. There were 115 women and 49 men with a mean age of 46 years.
      Embolization was successful in all patients. Procedural morbidity and mortality
      rates were 2.2% and 0% respectively. Immediate anatomical outcome included 54
      complete occlusion (29.5%), 43 neck remnants (23.5%) and 86 incomplete occlusions
      (47%). Imaging follow-up was available in 137 patients (mean=26 months, range 3
      to 99 months) and it showed 104 complete occlusions (75.9%), 23 neck remnants
      (16.8%) and 10 incomplete occlusions (7.3%). At follow-up, only 3 patients
      developed a significant intrastent stenosis, one of which was induced by
      radiosurgery. One of these patients had a symptomatic thrombo-embolic
      complication 3 years after stent placement. CONCLUSION: SAC of complex UIA is
      effective and associated with low complication rates. Even if immediate
      anatomical results are relatively unsatisfying, mid- and long-term follow-up show
      a major improvement with a high rate of adequate occlusion that is stable over
      time. Moreover, the long-term clinical and angiographic tolerance of intracranial
      stents is excellent.

PMID- 24462258
TI  - Endovascular treatment of acute ischemic stroke in France: a nationwide survey.
AB  - BACKGROUND AND PURPOSE: Developments in endovascular treatment have opened new
      promising prospects for treating acute ischemic stroke. In France, EVT is
      increasingly used, especially when intravenous thrombolysis is contraindicated or
      has failed. However, it has not been documented how neurointerventional centers
      are organized practically for the treatment of AIS. The present survey aims to
      address this. MATERIALS AND METHODS: The centers in France that are authorized to
      perform EVT for AIS were invited to participate to an electronic survey. The
      survey was composed of 33 questions, divided into 6 subheadings: (1) general
      information, (2) imaging modalities, (3) patient selection, (4) anesthesiology,
      (5) endovascular procedure and (6) imaging follow-up. RESULTS: The response rate
      was high at 93.9%. Neuroradiology centers are organized to perform mechanical
      thrombectomy around the clock in 80.6% of the institutions. MRI was the most
      commonly used imaging modality to examine acute stroke, alone in 64.5% or in
      combination with CT in 22.6%. The median number of neurointerventionalists was 3
      per center and the median number of procedures performed in 2012 was 925. Since
      the medical treatment is complex, an anesthesiologist is often required during
      the procedure (87.1%). Technical issues are also developed in the manuscript.
      CONCLUSIONS: This survey shows that French neuroradiology departments have made
      important efforts to implement EVT of AIS with a high quality of care for the
      patients; the majority of the centers used MRI to evaluate the disease and
      anesthesiologists are involved in order to optimize medical care during EVT.

PMID- 24462259
TI  - CT perfusion imaging insights in acute bilateral carotid occlusion.

PMID- 24462260
TI  - Anxiety, depression and personality traits in severe, prednisone-dependent
      asthma.
AB  - BACKGROUND: Anxiety and depression are prevalent in patients with asthma, and
      associated with more exacerbations and increased health care utilization. Since
      psychiatric intervention might improve asthma control, we examined whether
      patients with severe, prednisone-dependent asthma are at higher risk of these
      disorders than patients with severe non-prednisone dependent asthma or mild
      moderate asthma, and whether they exhibit different personality traits. METHODS:
      Sixty-seven adults with severe prednisone-dependent asthma, 47 with severe non
      prednisone dependent and 73 patients with mild-moderate asthma completed the HADS
      depression and anxiety subscale and the NEO-FFI for personality traits. In
      addition, asthma duration, body mass index and FEV1 were measured. RESULTS: The
      prevalence of clinically significant depressive symptoms (9% vs. 0 vs. 0%; p =
      0.009) and anxiety symptoms (19% vs. 6.4 vs. 5.5%; p = 0.01), was higher in
      patients with severe, prednisone-dependent asthma than in patients with severe
      non-prednisone dependent or mild-moderate asthma. Patients with prednisone
      dependent asthma were respectively 3.4 (95%CI: 1.0-10.8 p = 0.04) and 3.5 (95%CI:
      1.3-9.6 p = 0.01) times more likely to have significant depression symptoms and
      1.6 (95%CI: 0.7-3.7, p = 0.2) and 2.5 (95%CI: 01.1-5.5, p = 0.02) times more
      likely to have symptoms of anxiety than patients with severe non-prednisone
      dependent or mild-moderate asthma. There were no differences found in personality
      traits between the 3 groups. CONCLUSION: Patients with severe, prednisone
      dependent asthma have more often psychological distress as compared to patients
      with severe non-prednisone dependent or mild-moderate asthma.

PMID- 24462261
TI  - Cough suppression disorders spectrum.
AB  - Volitional cough suppression, identified exclusively in females, is an unusual
      causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a
      postulated mechanism for the genesis of Lady Windermere Syndrome. 

PMID- 24462262
TI  - Chronic and bedtime use of benztropine with antipsychotics: is it necessary?

PMID- 24462263
TI  - Allelic imbalance associated with the schizophrenia risk SNP rs1344706 indicates
      a cis-acting variant in ZNF804A.

PMID- 24462264
TI  - Brain structure in different psychosis risk groups in the Northern Finland 1986
      birth cohort.
AB  - We tested the hypothesis that family risk for psychosis (FR) and clinical risk
      for psychosis (CR) are associated with structural brain abnormalities, with
      increased deficits in those at both family risk and clinical risk for psychosis
      (FRCR). The study setting was the Oulu Brain and Mind Study, with subjects drawn
      from the Northern Finland 1986 Birth Cohort (n=9479) using register and
      questionnaire based screening, and interviews using the Structured Interview for
      Prodromal Symptoms. After this procedure, 172 subjects were included in the
      study, classified as controls (n=73) and three risk groups: FR excluding CR (FR,
      n=60), CR without FR (CR, n=26), and individuals at both FR and CR (FRCR, n=13).
      T1-weighted brain scans were acquired and processed in a voxel-based analysis
      using permutation-based statistics. In the comparison between FRCR versus
      controls, we found lower grey matter volume (GMV) in a cluster (1689 voxels at 
      4.00, -72.00, -18.00mm) covering both cerebellar hemispheres and the vermis. This
      cluster was subsequently used as a mask to extract mean GMV in all four groups:
      FR had a volume intermediate between controls and FRCR. Within FRCR there was an
      association between cerebellar cluster brain volume and motor function. These
      findings are consistent with an evolving pattern of cerebellar deficits in
      psychosis risk with the most pronounced deficits in those at highest risk of
      psychosis. 

PMID- 24462265
TI  - On the matter of synovial fluid lubrication: implications for Metal-on-Metal hip
      tribology.
AB  - Artificial articular joints present an interesting, and difficult, tribological
      problem. These bearing contacts undergo complex transient loading and multi axes
      kinematic cycles, over extremely long periods of time (>10 years). Despite
      extensive research, wear of the bearing surfaces, particularly metal-metal hips,
      remains a major problem. Comparatively little is known about the prevailing
      lubrication mechanism in artificial joints which is a serious gap in our
      knowledge as this determines film formation and hence wear. In this paper we
      review the accepted lubrication models for artificial hips and present a new
      concept to explain film formation with synovial fluid. This model, recently
      proposed by the authors, suggests that interfacial film formation is determined
      by rheological changes local to the contact and is driven by aggregation of
      synovial fluid proteins. The implications of this new mechanism for the
      tribological performance of new implant designs and the effect of patient
      synovial fluid properties are discussed. 

PMID- 24462266
TI  - Fortified foods are major contributors to nutrient intakes in diets of US
      children and adolescents.
AB  - BACKGROUND: Even in an era of obesity and dietary excess, numerous shortfall
      micronutrients have been identified in the diets of US children and adolescents.
      To help tailor strategies for meeting recommendations, it is important to know
      what foods contribute greatly to micronutrient intakes. Data are lacking on
      specific contributions made by added nutrients. OBJECTIVE: Our aims were to
      examine the impact of fortification on nutrient adequacy and excess among US
      children and adolescents and to rank food sources of added nutrient intake and
      compare rankings with those based on total nutrient intake from foods. DESIGN AND
      STATISTICAL ANALYSES: Data were from 7,250 respondents 2 to 18 years old in the
      National Health and Nutrition Examination Survey 2003-2006. Datasets were
      developed that distinguished nutrient sources: intrinsic nutrients in foods;
      added nutrients in foods; foods (intrinsic plus added nutrients); and total diet
      (foods plus supplements). The National Cancer Institute method was used to
      determine usual intakes of micronutrients by source. The impact of fortification
      on the percentages of children having intakes less than the Estimated Average
      Requirement and more than the Upper Tolerable Intake Level was assessed by
      comparing intakes from intrinsic nutrients to intakes from intrinsic plus added
      nutrients. Specific food sources of micronutrients were determined as sample
      weighted mean intakes of total and added nutrients contributed from 56 food
      groupings. The percentage of intake from each grouping was determined separately
      for total and added nutrients. RESULTS: Without added nutrients, a high
      percentage of all children/adolescents had inadequate intakes of numerous
      micronutrients, with the greatest inadequacy among older girls. Fortification
      reduced the percentage less than the Estimated Average Requirement for many,
      although not all, micronutrients without resulting in excessive intakes. Data
      demonstrated the powerful influence of fortification on food-source rankings.
      CONCLUSIONS: Knowledge about nutrient intakes and sources can help put dietary
      advice into a practical context. Continued monitoring of top food sources of
      nutrients and nutrient contributions from fortification will be important.

PMID- 24462267
TI  - Evaluation of web-based, self-administered, graphical food frequency
      questionnaire.
AB  - Computer-administered food frequency questionnaires (FFQs) can address
      limitations inherent in paper questionnaires by allowing very complex skip
      patterns, portion size estimation based on food pictures, and real-time error
      checking. We evaluated a web-based FFQ, the Graphical Food Frequency System
      (GraFFS). Participants completed the GraFFS, six telephone-administered 24-hour
      dietary recalls over the next 12 weeks, followed by a second GraFFS. Participants
      were 40 men and 34 women, aged 18 to 69 years, living in the Columbus, OH, area.
      Intakes of energy, macronutrients, and 17 micronutrients/food components were
      estimated from the GraFFS and the mean of all recalls. Bias (second GraFFS minus
      recalls) was -9%, -5%, +4%, and -4% for energy and percentages of energy from
      fat, carbohydrate, and protein, respectively. De-attenuated, energy-adjusted
      correlations (intermethod reliability) between the recalls and the second GraFFS
      for fat, carbohydrate, protein, and alcohol were 0.82, 0.79, 0.67, and 0.90,
      respectively; for micronutrients/food components the median was 0.61 and ranged
      from 0.40 for zinc to 0.92 for beta carotene. The correlations between the two
      administrations of the GraFFS (test-retest reliability) for fat, carbohydrate,
      protein, and alcohol were 0.60, 0.63, 0.73, and 0.87, respectively; among
      micronutrients/food components the median was 0.67 and ranged from 0.49 for
      vitamin B-12 to 0.82 for fiber. The measurement characteristics of the GraFFS
      were at least as good as those reported for most paper FFQs, and its high
      intermethod reliability suggests that further development of computer
      administered FFQs is warranted.

PMID- 24462268
TI  - The phylogenetic and ecological context of cultured and whole genome-sequenced
      planktonic bacteria from the coastal NW Mediterranean Sea.
AB  - Microbial isolates are useful models for physiological and ecological studies and
      can also be used to reassemble genomes from metagenomic analyses. However, the
      phylogenetic diversity that can be found among cultured marine bacteria may vary
      significantly depending on the isolation. Therefore, this study describes a set
      of 136 bacterial isolates obtained by traditional isolation techniques from the
      Blanes Bay Microbial Observatory, of which seven strains have had the whole
      genome sequenced. The complete set was compared to a series of environmental
      sequences obtained by culture-independent techniques (60 DGGE sequences and 303
      clone library sequences) previously obtained by molecular methods. In this way,
      each isolate was placed in both its "ecological" (time of year, nutrient
      limitation, chlorophyll and temperature values) context or setting, and its
      "phylogenetic" landscape (i.e. similar organisms that were found by culture
      independent techniques, when they were relevant, and when they appeared). Nearly
      all isolates belonged to the Gammaproteobacteria, Alphaproteobacteria, or the
      Bacteroidetes (70, 40 and 20 isolates, respectively). Rarefaction analyses showed
      similar diversity patterns for sequences from isolates and molecular approaches,
      except for Alphaproteobacteria where cultivation retrieved a higher diversity per
      unit effort. Approximately 30% of the environmental clones and isolates formed
      microdiversity clusters constrained at 99% 16S rRNA gene sequence identity, but
      the pattern was different in Bacteroidetes (less microdiversity) than in the
      other main groups. Seventeen cases (12.5%) of nearly complete (98-100%) rRNA
      sequence identity between isolates and environmental sequences were found: nine
      in the Alphaproteobacteria, five in the Gammaproteobacteria, and three in the
      Bacteroidetes, indicating that cultivation could be used to obtain at least some
      organisms representative of the various taxa detected by molecular methods.
      Collectively, these results illustrated the largely unexplored potential of
      culturing on standard media for complementing the study of microbial diversity by
      culture-independent techniques and for obtaining phylogenetically distinct model
      organisms from natural seawater. 

PMID- 24462269
TI  - [Detection of Epstein-Barr virus in an inflammatory myofibroblastic tumor of the
      spleen (inflammatory pseudotumor)].

PMID- 24462270
TI  - The learning curve of laparoscopic treatment of rectal cancer does not increase
      morbidity.
AB  - INTRODUCTION: The treatment of rectal cancer via laparoscopy is controversial due
      to its technical complexity. Several randomized prospective studies have
      demonstrated clear advantages for the patient with similar oncological results to
      those of open surgery, although during the learning of this surgical technique
      there may be an increase in complications and a worse prognosis. OBJECTIVE: Our
      aim is to analyze how the learning curve for rectal cancer via laparoscopy
      influences intra- and postoperative results and oncological markers. A
      retrospective review was conducted of the first 120 patients undergoing
      laparoscopic surgery for rectal neoplasia. The operations were performed by the
      same surgical team with a wide experience in the treatment of open colorectal
      cancer and qualified to perform advanced laparoscopic surgery. We analyzed sex,
      ASA, tumour location, neoadjuvant treatment, surgical technique, operating time,
      conversion, postoperative complications, length of hospital stay, number of lymph
      nodes, stage and involvement of margins. RESULTS: Significant differences were
      observed with regard to surgical time (224 min in the first group, 204 min in the
      second group), with a higher rate of conversion in the first group (22.5%) than
      in the second (11.3%). No significant differences were noted for rate of
      conservative sphincter surgery, length of hospital stay, post-surgical
      complications, number of affected/isolated lymph nodes or affected
      circumferential and distal margins. CONCLUSIONS: It is possible to learn this
      complex surgical technique without compromising the patient's safety and
      oncological outcome.

PMID- 24462271
TI  - Residential neighborhood, geographic work environment, and work economic sector:
      associations with body fat measured by bioelectrical impedance in the RECORD
      Study.
AB  - PURPOSE: Studies of associations between geographic environment and obesity have
      mostly examined body mass index and focused on residential neighborhoods. We
      investigated associations between residential neighborhoods, geographic work
      environments, and work economic sectors and the fat mass index (FMI) and
      percentage of fat mass (%FM). METHODS: Data on 4331 participants from the French
      RECORD Study geolocated at their residence and workplace were analyzed. Body
      composition was assessed by bioelectrical impedance analyzers. Multilevel linear
      regression was used to investigate the determinants of FMI and %FM. RESULTS:
      After adjustment, among men, the FMI and %FM increased independently with
      decreasing density of population and educational level in the residential
      neighborhood. Among women, the residential educational level was related to the
      FMI and %FM. Among men, a higher FMI and %FM were observed among participants
      working in the construction and transportation/communication sectors than in the
      education sector. For women, the FMI was higher among participants working in the
      public administration and health/social work sectors than in the
      transport/communication sector. A long home-work distance was associated with a
      higher FMI among women. There was evidence that body mass index cannot fully
      capture work economic sector effects on fat mass. CONCLUSIONS: Public health
      interventions to reduce social/territorial disparities in obesity should also
      consider the different contexts to which the participants belong, such as
      residential environments and work economic sectors.

PMID- 24462272
TI  - Employment status, depressive symptoms, and waist circumference change in midlife
      women: the Study of Women's Health Across the Nation (SWAN).
AB  - PURPOSE: Changes in employment status have shown inconsistent associations with
      adiposity. This study tested whether the presence of elevated depressive symptoms
      explains variability in the time-varying association between employment status
      and central adiposity. METHOD: Employment status, depressive symptoms, and waist
      circumference (WC) were assessed annually over 10 years in a multiethnic sample
      of 3220 midlife women enrolled in the Study of Women's Health Across the Nation.
      Linear mixed-effects models tested time-varying associations of employment
      status, depressive symptoms, and their interaction with WC. RESULTS: WC increases
      were greatest during the years of combined nonemployment and elevated depressive
      symptoms (1.00 cm/y) and lowest in the years of full-time employment and elevated
      depressive symptoms (0.25 cm/y), compared with the years of full-time employment
      and nonelevated depressive symptoms (0.51 cm/y). Employment status was unrelated
      to WC in years without elevated depressive symptoms. The pattern of results was
      unchanged when analyses were restricted to preretirement observations and did not
      vary according to WC at baseline or ethnicity/race. CONCLUSIONS: Identifying and
      managing depressive symptoms in midlife women who are not working may help
      prevent increases in central adiposity.

PMID- 24462273
TI  - Disparities in breast cancer stage at diagnosis in urban and rural adult women: a
      systematic review and meta-analysis.
AB  - PURPOSE: Survival from breast cancer is dependent on stage at diagnosis and some
      evidence suggests that rural women are more likely than urban women to be
      diagnosed with advanced stage disease. This systematic review and meta-analysis
      compared the stage of breast cancer at diagnosis between women residing in urban
      and rural areas. METHODS: PubMed (1951-2012), EMBASE (1966-2012), CINAHL (1982
      2012), RURAL (1966-2012), and Sociological abstracts (1952-2012) were
      systematically searched in November 2012 for relevant peer reviewed studies.
      Studies on adult women were included if they reported quantitative comparisons of
      rural and urban differences in staging of breast cancer at diagnosis. RESULTS:
      Twenty-four studies were included in the systematic review and 21 studies had
      sufficient information for inclusion in the meta-analysis (N = 879,660). Evidence
      indicated that patients residing in rural areas were more likely to be diagnosed
      with more advanced breast cancer. Using a random effects model, the results of
      the meta-analysis showed that rural breast cancer patients had 1.19 higher odds
      (95% confidence interval, 1.12-1.27) of late stage breast cancer compared with
      urban breast cancer patients. CONCLUSIONS: Rural women were more likely than
      urban women to be diagnosed at a later stage. Preventive measures may need to
      target the rural population.

PMID- 24462274
TI  - Psychiatric diseases predated the occurrence of Parkinson disease: a
      retrospective cohort study.
AB  - PURPOSE: The influence of mental illness early in life on the subsequent risk of
      Parkinson disease (PD) and its clinical picture remain obscure. This study
      investigated the effects of psychiatric diseases on a subsequent PD diagnosis.
      METHODS: We used the Longitudinal Health Insurance Database 2000 of Taiwan to
      identify 73,597 patients who visited ambulatory care centers or were hospitalized
      with a first-time diagnosis of anxiety, affective disorders, or schizophrenia
      between 2001 and 2003 as the study cohort. We also randomly selected 220,791
      enrollees matched with the study cohort for comparison. Each patient was
      individually tracked for 6 years to identify a subsequent PD diagnosis.
      Stratified Cox proportional hazard regressions were performed for the analysis.
      RESULTS: The incidence rate of PD per 1000 person-years was 4.91 (95% confidence
      interval [CI], 4.71-5.12) and 1.63 (95% CI, 1.56-1.70) for the psychiatric and
      comparison groups, respectively. Patients with psychiatric illnesses were more
      vulnerable to developing PD than nonpsychiatric individuals, exhibiting a 2.38
      fold increased risk (95% CI, 2.23-2.53) after other covariates were considered.
      Furthermore, patients with schizophrenia exhibited the highest risk for
      developing PD. CONCLUSIONS: We suggest effective monitoring of patients with
      psychiatric disturbances for potential long-term neurodegenerative diseases.

PMID- 24462275
TI  - [Hepatocyte transplantation: regenerative potential and limitations].

PMID- 24462276
TI  - [Reply].

PMID- 24462277
TI  - Hepatitis C virus core protein regulates NANOG expression via the stat3 pathway.
AB  - HCV Core plays a role in the development of hepatocellular carcinoma. Aberrant
      expression of NANOG has been observed in many types of human malignancies.
      However, relationship between Core and NANOG has not been clarified. In this
      study, we found that Core is capable of up-regulating NANOG expression. Core
      induced NANOG expression was accompanied by enforced expression of phosphorylated
      stat3 protein and was attenuated by inhibition of stat3 phosphorylation. ChIP
      showed that phosphorylated stat3 directly binds to the NANOG promoter. Core
      induced NANOG expression resulted in enhanced cell growth and cell cycle
      progression. Knockdown of NANOG blocked the cell cycle at the G0/G1 phases and
      inhibited the cyclin D1 expression. Our findings provide a new insight into the
      mechanism of hepatocarcinogenesis by HCV infection. 

PMID- 24462278
TI  - Cationorm shows good tolerability on human HCE-2 corneal epithelial cell
      cultures.
AB  - Preservatives have been for a long time known to cause detrimental effects on
      ocular surface. Cationorm, a preservative-free compound with electrostatic
      properties is a novel way to solve the problems encountered with traditional
      benzalkonium chloride (BAK)-containing eye drops. The aim of this study was to
      evaluate tolerability of the preservative-free cationic emulsion Cationorm in
      vitro on corneal epithelial cells. The human corneal epithelial cell (HCE-2)
      culture line was used to study cellular morphology, cytotoxicity and inflammatory
      responses after Cationorm diluted 1/10 exposure for 5, 15 and 30 min. Exposures
      to Systane diluted 1/10 with polyquaternium-1/polidronium chloride 0.001% as
      preservative, BAK 0.001% or C16 (0.0002%) and normal cell culture medium served
      as positive and negative references. Cell viability was determined by measuring
      the release of lactate dehydrogenase (LDH) and mitochondrial dehydrogenase
      activity was evaluated using 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. The possible induction of apoptosis was analyzed by
      measuring the activity of caspase-3, and Cell Counting Kit-8 (CCK-8) was used to
      evaluate the number of viable cells after the exposure to test compounds.
      Furthermore, the tendency of the test compounds to produce inflammatory reaction
      was determined by analyzing the production of proinflammatory cytokines IL-6 and
      IL-8, and DNA binding of the p65 subunit of transcription factor NF-kappaB was
      measured from cell lysates. HCE-2 cells showed no morphological changes after the
      exposure to Cationorm, but in cells exposed to BAK, clear cytoplasm vacuolization
      and loose cell-cell contacts were observed in transmission (TEM) or scanning
      (SEM) electron microscopic analyses. Cell viability, as measured with the release
      of LDH, indicated a time dependent increase in LDH expression after exposure to
      all test compounds but especially with BAK. Moreover, Cationorm and BAK time
      dependently decreased the mitochondrial metabolism to 73% with Cationorm and 53%
      with BAK from that of the control cells after 30 min exposure in MTT assay. BAK
      was the only test compound having clear adverse effects on the cell number and
      metabolism in CCK-8 assay. The activity of caspase-3 did not show significant
      differences between the groups. Inflammatory response after exposure to Cationorm
      was significantly lower than after exposure to BAK. There were no significant
      differences in NF-kappaB activity between the groups. Diluted Cationorm and
      Systane with polyquaternium-1/polidronium chloride 0.001% showed good
      tolerability on HCE-2 cells and thereby provide a clear improvement when compared
      to BAK-containing eye drop formulations. 

PMID- 24462279
TI  - [Duodenal duplication cyst and its endoscopic resolution].

PMID- 24462280
TI  - [Acute on chronic liver failure: A new concept for a classic complication].

PMID- 24462281
TI  - Glycaemic control in insulin requiring diabetes patients receiving exclusive
      enteral tube feeding in an acute hospital setting.
AB  - AIMS: Optimising glycaemic control for insulin requiring individuals during
      enteral feeding is important but difficult. We compare 3 insulin regimens with
      the aim of improving glucose control and reducing hypoglycaemia. METHODS:
      Comparison of 3 insulin/feed regimens: (1) A 20 h feed using a 30:70 premixed
      insulin (2) Three bolus (4 h) feeds combined with short acting analogue insulin
      and a basal long acting insulin. (3) A 24 h feed combined with a long acting
      analogue insulin. The study combined a retrospective analysis of regimen (1) with
      consecutive prospective analyses of (2) and (3). RESULTS: Glucose concentrations
      were suboptimal with higher values during the feeds (12.6 mmol/L +/- 4.4 vs 10.3
      +/- 4.1 p<0.001). Although there was no overall difference in glucose control
      between groups there was a reduction in hypoglycaemia during the feed in the
      bolus group (no hypoglycaemia during intermittent feeds p<0.001). CONCLUSIONS:
      Glucose concentrations were relatively high overall. Short bolus feeding appears
      to reduce the frequency of hypoglycaemia. This is of clinical significance for
      this patient group.

PMID- 24462282
TI  - Prevention by metformin of alterations induced by chronic exposure to high
      glucose in human islet beta cells is associated with preserved ATP/ADP ratio.
AB  - AIM: We have explored whether the insulin secretory defects induced by
      glucotoxicity in human pancreatic islets could be prevented by metformin and
      investigated some of the possible mechanisms involved. METHODS: Human pancreatic
      islets and INS-1E cells were cultured for 24h with or without high glucose
      (16.7mM) concentration in the presence or absence of therapeutical concentration
      of metformin and then glucose-stimulated insulin release, adenine nucleotide
      levels and mitochondrial complex I and II activities were measured. Islet
      ultrastructure was analyzed by electron microscopy. RESULTS: Compared to control
      islets, human islets cultured with high glucose showed a reduced glucose
      stimulated insulin secretion that was associated with lower ATP levels and a
      lower ATP/ADP ratio. These functional and biochemical defects were significantly
      prevented by the presence of metformin in the culture medium, that was also able
      to significantly inhibit the activity of mitochondrial complex I especially in
      beta cells exposed to high glucose. Ultrastructural observations showed that
      mitochondrial volume density was significantly increased in high glucose cultured
      islets. The critical involvement of mitochondria was further supported by the
      observation of remarkably swollen organelles with dispersed matrix and fragmented
      cristae. Metformin was able to efficiently prevent the appearance of all these
      ultrastructural alterations in human islets exposed to high glucose. CONCLUSIONS:
      Our results show that the functional, biochemical and ultrastructural
      abnormalities observed in human islet cells exposed to glucotoxic condition can
      be significantly prevented by metformin, further highlighting a direct beneficial
      effect of this drug on the insulin secreting human pancreatic beta cells.

PMID- 24462283
TI  - Outcomes of popliteal vascular injuries at Sri Lankan war-front military
      hospital: case series of 44 cases.
AB  - BACKGROUND AND AIMS: Traumatic injury to the popliteal vascular zone remains a
      challenging problem on the modern battlefield and is frequently associated with
      more complications than other vascular injuries. Limb salvage and morbidity
      (graft infection, thrombosis and delayed haemorrhage) were studied. MATERIALS AND
      METHODS: All popliteal vascular injuries over an 8 month period admitted to the
      Military Base Hospital were analyzed. Local limb evaluation included confirmation
      of the presence of ischaemia, extent of soft tissue damage, muscle viability
      after calf fasciotomy, and neurological injury. Ischaemic time was recorded from
      the time of injury to definitive revascularization. If there was a prior attempt
      at reconstruction, the amputation was considered delayed. RESULTS: For a series
      of 44 patients with popliteal vascular injury average time to presentation was
      390min, 46% were completely ischaemic. Of those 39 (89%) had popliteal artery
      injuries. There were 24 (62%) complete popliteal artery transections and
      associated venous (69%) and osseous (46%) injuries. The preferred technique of
      repair was inter-position venous graft (IPVG) (54%). Eleven immediate amputations
      were performed (28%). There were 13 wound infections (33%), 5 early graft
      thromboses (5 of 21 IPVG, 238%), 2 anastomotic disruptions (2 of 21 IPVG, 9%),
      which resulted in 4 delayed amputations. Mortality was 5% (2 patients).
      CONCLUSIONS: In this case series of popliteal artery injury early identification
      of limbs at risk, early four compartment fasciotomy, temporary intra-luminal
      shunting, definitive repair of concomitant venous injuries and aggressive
      treatment of haemodynamic instability were shown to be beneficial in achieving
      reasonable outcome in an austere environment with limited recourses.

PMID- 24462284
TI  - Pre-operative tumour marker status predicts recurrence and survival after
      complete cytoreduction and hyperthermic intraperitoneal chemotherapy for
      appendiceal Pseudomyxoma Peritonei: Analysis of 519 patients.
AB  - BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic
      Intraperitoneal Chemotherapy (HIPEC) is the optimal treatment for Pseudomyxoma
      Peritonei (PMP). Despite treatment, disease often recurs and may not be amenable
      to further CRS. Clinical experience suggests a spectrum of disease which may
      correlate with tumour marker levels. The aim of this study was to analyse the
      influence of markers on recurrence and survival. METHODS: The details of all
      patients undergoing surgery for PMP of appendiceal origin at a national centre
      for peritoneal malignancy were recorded in a dedicated prospective database. The
      data on all patients who had CRS and HIPEC between March 1994 and January 2012
      was analysed and recurrence and survival correlated with pre-operative levels of
      CEA, CA-125 and CA19-9. RESULTS: Overall, 519 (69%) of 752 consecutive patients,
      underwent complete CRS and HIPEC. The median (range) age was 56 (20-82) years
      with 342/519 (66%) females. The mean overall (OS) and disease free survival (DFS)
      in the 131/519 patients who had normal preoperative tumour markers was 168 (128
      207) and 125 (114-136) months respectively, significantly higher when compared
      with the 109/519 (21%) who had all three tumour markers elevated (OS of 65 (42
      88) and DFS of 55 (41-70) months respectively) (P = 0.002). CONCLUSIONS: Elevated
      tumour markers predict an increased risk of recurrence and reduced survival after
      complete CRS. This may reflect cell biology in low grade tumours and is an
      independent prognostic feature. Further analysis may help to select patients for
      post-operative chemotherapy, second look procedures or stratification of follow
      up.

PMID- 24462285
TI  - [The dorsal nerve of the clitoris: surgical applications].
AB  - OBJECTIVES: To describe the course of the dorsal nerve of the clitoris (DNC) to
      better define its anatomy in the human adult and to help surgeons to avoid
      iatrogenic injury during surgical procedures. METHOD: An extensive review of the
      current literature was done on Medline via PubMed by using the following
      keywords: "anatomie du clitoris", "anatomy of clitoris", "nerf dorsal du
      clitoris", "dorsal nerve of clitoris", "reparation clitoridienne", "transposition
      clitoridienne", "surgery of the clitoris", "clitoridoplasty". This review
      analyzed dissection, magnetic resonance imaging, 3-dimensional sectional anatomy
      reconstruction and immuno-histochemical studies. RESULTS: The DNC comes from the
      pudendal nerve. He travels from under the inferior pubis ramus to the
      posterosuperior edge of the clitoral crus. The DNC reappears under the pubic
      symphysis and enters the deep component of the suspensory ligament. He runs on
      the dorsal face of the clitoral body at 11 and 1 o'clock. Distally, he gives many
      nervous ramifications, runs along the tunica and enters the glans. CONCLUSION:
      The NDC might be surgically injured (i) under the pubic symphysis, at the union
      of the two crus of clitoris and (ii) on the dorsal surface of the clitoral body.
      The pathway of the DNC on the dorsal face of the clitoris permits to approach the
      ventral face of the clitoris without risk of iatrogenic injuries. The distance
      between the pubic symphysis and the DNC implies that the incision should be done
      just under the pubic symphysis. Distally, the dissection of the DNC next the
      glands appears as dangerous and impossible, considering that the DNC is too close
      to the glandular tissues.

PMID- 24462286
TI  - Gadolinium-loaded chitosan nanoparticles for neutron-capture therapy: Influence
      of micrometric properties of the nanoparticles on tumor-killing effect.
AB  - As a nanoparticulate device for controlled delivery of Gd in NCT, the authors
      have developed gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs). In the
      present study, influence of micrometric properties such as particle size,
      particle-surface charge and Gd content of Gd-nanoCPs on tumor-killing effect by
      Gd-NCT was investigated with Gd-nanoCPs. Two types of Gd-nanoCPs with different
      mean particle size, zeta potential and Gd-content (Gd-nanoCP-400; 391nm, 28mV,
      9wt% and Gd-nanoCP-200; 214nm, 19mV, 24wt%) could be prepared by using chitosans
      with different molecular weights. Gd-nanoCPs incorporating 1.2mg of natural Gd
      were injected intratumorally once or twice to mice subcutaneously-bearing B16F10
      melanoma. Eight hours after the last administration, thermal neutron was
      irradiated to tumor region of the mice. Remarkable tumor-growth was observed in
      both hot and cold control groups. In contrast, Gd-NCT groups showed significant
      tumor-growth suppression effect, though their efficacy was found to depend on the
      micrometric properties of Gd-nanoCPs. In particular, the Gd-nanoCP-200 exhibited
      stronger tumor-killing effect than the Gd-nanoCP-400 at the same Gd dose and it
      was still similar to Gd-nanoCP-400 in tumor-growth suppressing effect even at the
      half of Gd dose of Gd-nanoCP-400. This significance in tumor-killing effect would
      be ascribed from a higher Gd retention in the tumor tissue and an improved
      distribution of Gd with intratumorally administered Gd-nanoCP-200. Indeed, the Gd
      concentration in tumor tissue at the time corresponding to the onset of thermal
      neutron irradiation was determined to be significantly higher in Gd-nanoCP-200,
      compared with Gd-nanoCP-400. These results demonstrated that appropriate
      modification of Gd-nanoCPs in micrometric properties would be an effective way to
      improve the retention of Gd in the tumor tissue after intratumoral injection,
      leading to the enhanced tumor-killing effect in Gd-NCT. 

PMID- 24462287
TI  - Recycling endosome tubule morphogenesis from sorting endosomes requires the
      kinesin motor KIF13A.
AB  - Early endosomes consist of vacuolar sorting and tubular recycling domains that
      segregate components fated for degradation in lysosomes or reuse by recycling to
      the plasma membrane or Golgi. The tubular transport intermediates that constitute
      recycling endosomes function in cell polarity, migration, and cytokinesis.
      Endosomal tubulation and fission require both actin and intact microtubules, but
      although factors that stabilize recycling endosomal tubules have been identified,
      those required for tubule generation from vacuolar sorting endosomes (SEs) remain
      unknown. We show that the microtubule motor KIF13A associates with recycling
      endosome tubules and controls their morphogenesis. Interfering with KIF13A
      function impairs the formation of endosomal tubules from SEs with consequent
      defects in endosome homeostasis and cargo recycling. Moreover, KIF13A interacts
      and cooperates with RAB11 to generate endosomal tubules. Our data illustrate how
      a microtubule motor couples early endosome morphogenesis to its motility and
      function. 

PMID- 24462288
TI  - Specificity and commonality of the phosphoinositide-binding proteome analyzed by
      quantitative mass spectrometry.
AB  - Phosphoinositides (PIPs) play key roles in signaling and disease. Using high
      resolution quantitative mass spectrometry, we identified PIP-interacting proteins
      and profiled their binding specificities toward all seven PIP variants. This
      analysis revealed 405 PIP-binding proteins, which is greater than the total
      number of phospho- or ubiquitin-binding domains. Translocation and inhibitor
      assays of identified PIP-binding proteins confirmed that our methodology targets
      direct interactors. The PIP interactome encompasses proteins from diverse
      cellular compartments, prominently including the nucleus. Our data set revealed a
      consensus motif for PI(3,4,5)P3-interacting pleckstrin homology (PH) domains,
      which enabled in silico identification of phosphoinositide interactors. Members
      of the dedicator of cytokinesis family C exhibited specificity toward both
      PI(3,4,5)P3 and PI(4,5)P2. Structurally, this dual specificity is explained by a
      decreased number of positively charged residues in the L1 subdomain compared with
      DOCK1. The presented PIP-binding proteome and its specificity toward individual
      PIPs should be a valuable resource for the community.

PMID- 24462289
TI  - High Runx1 levels promote a reversible, more-differentiated cell state in hair
      follicle stem cells during quiescence.
AB  - Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early
      progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying
      matrix cells. EPs can revert to SCs upon injury, but whether this
      dedifferentiation occurs in normal HF homeostasis (hair cycle) and the mechanisms
      regulating both differentiation and dedifferentiation are unclear. Here, we use
      lineage tracing, gain of function, transcriptional profiling, and functional
      assays to examine the role of observed endogenous Runx1 level changes in the hair
      cycle. We find that forced Runx1 expression induces hair degeneration (catagen)
      and simultaneously promotes changes in the quiescent bulge SC transcriptome
      toward a cell state resembling the EP HG fate. This cell-state transition is
      functionally reversible. We propose that SC differentiation and dedifferentiation
      are likely to occur during normal HF degeneration and niche restructuring in
      response to changes in endogenous Runx1 levels associated with SC location with
      respect to the niche. 

PMID- 24462290
TI  - Conservation of mRNA and protein expression during development of C. elegans.
AB  - Spatiotemporal control of gene expression is crucial for development and subject
      to evolutionary changes. Although proteins are the final product of most genes,
      the developmental proteome of an animal has not yet been comprehensively defined,
      and the correlation between mRNA and protein abundance during development is
      largely unknown. Here, we globally measured and compared protein and mRNA
      expression changes during the life cycle of the nematodes C. elegans and C.
      briggsae, separated by ~30 million years of evolution. We observed that
      developmental mRNA and protein changes were highly conserved to a surprisingly
      similar degree but were poorly correlated within a species, suggesting important
      and widespread posttranscriptional regulation. Posttranscriptional control was
      particularly well conserved if mRNA fold changes were buffered on the protein
      level, indicating a predominant repressive function. Finally, among divergently
      expressed genes, we identified insulin signaling, a pathway involved in lifespan
      determination, as a putative target of adaptive evolution.

PMID- 24462291
TI  - TOR complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and
      regulating ROS accumulation.
AB  - Reactive oxygen species (ROS) are produced during normal metabolism and can
      function as signaling molecules. However, ROS at elevated levels can damage
      cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2)/Ypk1
      signaling module as an important regulator of ROS in the model eukaryotic
      organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by
      mitochondria as well as by nonmitochondrial sources, including changes in
      acidification of the vacuole. Furthermore, we link vacuole-related ROS to
      sphingolipids, essential components of cellular membranes, whose synthesis is
      also controlled by TORC2/Ypk1 signaling. In total, our data reveal that
      TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels
      and that ROS are a critical regulatory signal within this system. Thus, ROS
      sensing and signaling by TORC2/Ypk1 play a central physiological role in
      sphingolipid biosynthesis and in the maintenance of cell growth and viability.

PMID- 24462292
TI  - The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes
      switch-like conformational changes in the activation loop.
AB  - The presence of DNA in the cytoplasm is a danger signal that triggers immune and
      inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP
      (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds
      to the adaptor protein STING and activates a signaling cascade that leads to the
      production of type I interferons and other cytokines. Here, we report the crystal
      structures of human cGAS in its apo form, representing its autoinhibited
      conformation as well as in its cGAMP- and sulfate-bound forms. These structures
      reveal switch-like conformational changes of an activation loop that result in
      the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals
      a complex composed of dimeric cGAS bound to two molecules of DNA. Functional
      analyses of cGAS mutants demonstrate that both the protein-protein interface and
      the two DNA binding surfaces are critical for cGAS activation. These results
      provide insights into the mechanism of DNA sensing by cGAS. 

PMID- 24462293
TI  - Inference of tumor evolution during chemotherapy by computational modeling and in
      situ analysis of genetic and phenotypic cellular diversity.
AB  - Cancer therapy exerts a strong selection pressure that shapes tumor evolution,
      yet our knowledge of how tumors change during treatment is limited. Here, we
      report the analysis of cellular heterogeneity for genetic and phenotypic features
      and their spatial distribution in breast tumors pre- and post-neoadjuvant
      chemotherapy. We found that intratumor genetic diversity was tumor-subtype
      specific, and it did not change during treatment in tumors with partial or no
      response. However, lower pretreatment genetic diversity was significantly
      associated with pathologic complete response. In contrast, phenotypic diversity
      was different between pre- and posttreatment samples. We also observed
      significant changes in the spatial distribution of cells with distinct genetic
      and phenotypic features. We used these experimental data to develop a stochastic
      computational model to infer tumor growth patterns and evolutionary dynamics. Our
      results highlight the importance of integrated analysis of genotypes and
      phenotypes of single cells in intact tissues to predict tumor evolution. 

PMID- 24462295
TI  - Early-onset of multiple sclerosis in a 5-year-old girl.
AB  - Childhood multiple sclerosis is a rare demyelinating autoimmune disease with
      particular features. Onset of multiple sclerosis is extremely uncommon in early
      childhood, particularly before 6 years of age. We report the case of a 5-year-old
      girl admitted to the hospital for altered consciousness and rapid onset of right
      hemiparaplegia. Magnetic resonance imaging (MRI) of the brain showed multifocal
      white matter disease with T2 hyperintense oval lesions in subcortical,
      periventricular, and cerebellar hemispheres. Treatment with high dose intravenous
      methylprednisolone (30 mg/kg/day for 3 days) improved symptoms. Intravenous
      corticosteroid therapy was followed by 1mg/kg/day of oral prednisone. A second
      MRI, 40 days later, revealed new disseminated T2 hyperintense lesions in the
      frontal periventricular white matter, corpus callosum, left middle cerebellar
      peduncle, and dorsal spinal cord, leading to the diagnosis of multiple sclerosis.
      Azathioprine (2.5 mg/kg/day) was started and the steroid dose was tapered before
      being stopped after 3 months. After 2 years of follow-up, the patient has
      remained asymptomatic with a normal neurological exam and with no relapse or side
      effects of azathioprine. This work shows the particularities in clinical and
      radiological features of multiple sclerosis in a child aged less than 6 years.

PMID- 24462296
TI  - [Pediatric SIGAPS scoring].

PMID- 24462294
TI  - Effect of cholecalciferol recommended daily allowances on vitamin D status and
      fibroblast growth factor-23: an observational study in acute burn patients.
AB  - OBJECTIVE: Burn patients are at risk of hypovitaminosis D. Optimal vitamin D (VD)
      intakes are not defined in burn nutrition guidelines and studies mostly focused
      on ergocalciferol (VD2) supplementation in burn children. Aim of our study was to
      describe adult burns VD status, to measure effects of our cholecalciferol (VD3)
      supplementation on VD metabolism during acute burn care, and to assess
      correlation between FGF23 and C-reactive protein (CRP). DESIGN: Cohort study.
      METHODS: From March 2012 to January 2013, patients >18 years, admitted within 24
      h after injury with burn surface area (BSA) >=10% were included. Patients daily
      received VD3 from oral or enteral nutrition (400-600 IU) and from oral or
      intravenous multivitamin complex (200-220 IU). Serum levels of 25(OH)-D, 1
      25(OH)2-D, 3rd generation PTH, C-terminal FGF23, total calcium, phosphate,
      albumin and CRP were measured at admission (D0) and every week during 4 weeks of
      follow-up. Data are expressed as percentage or median (min-max). Paired data were
      compared using Wilcoxon test. Correlation between CRP and FGF23 was assessed
      using nonparametric Spearman test. A p value <0.05 was considered to be
      statistically significant. RESULTS: We initially included 24 patients. Median age
      and BSA were, respectively, 46 [19-86] years and 15 [10-85]%. At D0, 75%
      presented a VD insufficiency (25(OH)-D 21-29 ng/ml) and 17% presented a
      deficiency (25(OH)-D <=20 ng/ml). We followed 12 patients until day 28: 25(OH)-D
      was unchanged while 1-25(OH)2-D and FGF23 decreased without reaching
      significance. We observed a significant positive correlation between FGF23 and
      CRP (r=0.59, 95% CI: 0.22-0.82, p=0.0032). CONCLUSIONS: Most of our adult burns
      presented hypovitaminosis D regardless of age. Nutrition supplemented with low
      dose of VD3 (intakes reaching recommended daily allowances) was insufficient to
      correct 25(OH)-D level. Moreover, an interesting correlation between CRP and
      FGF23 was found.

PMID- 24462297
TI  - [Is pediatrics excluded from pharmaceutical innovation?].
AB  - OBJECTIVE: The development of therapeutic strategies for children depends
      unequivocally on the commercial launching of drugs with pediatric indications.
      New therapeutic drugs differ from one country to another, particularly
      considering children. The objective of this study was to compare access to new
      drugs by children in France (FR) and Canada (CA). MATERIAL AND METHODS:
      Retrospective study comparing newly marketed drugs in FR and CA from 1 January to
      31 December 2009. Data were collected through independent sources: (HAS,
      Theriaque, ANSM for FR and CEPMB, BDPP for CA). RESULTS: Respectively, 37 and 30
      new drugs were put on the market in 2009 in FR and CA. Among them, 38% (n=14) and
      27% (n=8) had a pediatric indication. For 91% (FR) and 95% (CA) of the drugs not
      indicated for children, no clinical study has been planned to define pediatric
      indications. All the drugs (100%) with pediatric indications presented dosages
      based on age or weight, but it should be noted that two drugs had no form adapted
      to children. Fifty-seven percent of these drugs were first available on the
      French market and later on the Canadian market, with a median delay of 8.5months.
      CONCLUSION: This study highlights the obvious lack of pediatric drugs
      contributing to large prescriptions of off-label drugs for children, with no
      dosage or adapted pharmaceutical form for this population.

PMID- 24462298
TI  - IgG, IgA, and lysozyme in Martina Franca donkey jennies and their foals.
AB  - Because immune transfer from jenny to donkey foal is mostly unknown, the aim of
      the present study was to evaluate, from 5 days before to 10 days after foaling,
      immunoglobulin (Ig)G, IgA, and lysozyme peripartal concentrations in serum and
      mammary secretions of 10 healthy, spontaneously foaling Martina Franca jennies
      and in serum of their mature, viable, healthy foals, in the first 10 days after
      birth. The results showed that, in jennies, mammary secretion of IgG levels
      (ranging between 16 and 75 mg/mL) and IgA (0.9-2 mg/mL), and IgG (6.8-13.5 mg/mL)
      and IgA (0.5-2.4 mg/mL) serum concentrations were not different along the time of
      study. Also, IgG concentrations in serum of foals did not show significant
      differences although a high level was observed at 12 hours after birth (8 mg/mL),
      and IgA concentrations in serum of foals did not show any significant difference,
      although a high level was observed at 12 hours after birth (1.2 mg/mL). Lysozyme
      increased significantly at Day 2 after parturition in mammary secretions of
      jennies (551.9 MUg/mL) and at 12 hours in serum of foals (25.9 MUg/mL). The study
      demonstrated that the pattern of passive immune transfer in donkey foals seems to
      be similar to that reported for the horse foal, with IgG predominating IgA in
      serum and mammary secretions of the jenny and also in serum of foals. The most
      significant early increase in foals' serum concerns lysozyme, which probably
      plays an important role in the innate immunity of the donkey foal in the first
      challenging hours after birth. 

PMID- 24462299
TI  - The effects of superovulation of donor sows on ovarian response and embryo
      development after nonsurgical deep-uterine embryo transfer.
AB  - This study aimed to evaluate the effectiveness of superovulation protocols in
      improving the efficiency of embryo donors for porcine nonsurgical deep-uterine
      (NsDU) embryo transfer (ET) programs. After weaning (24 hours), purebred Duroc
      sows (2-6 parity) were treated with 1000 IU (n = 27) or 1500 IU (n = 27) of eCG.
      Only sows with clear signs of estrus 4 to 72 hours after eCG administration were
      treated with 750 IU hCG at the onset of estrus. Nonhormonally treated postweaning
      estrus sows (n = 36) were used as a control. Sows were inseminated and subjected
      to laparotomy on Days 5 to 6 (Day 0 = onset of estrus). Three sows (11.1%)
      treated with the highest dosage of eCG presented with polycystic ovaries without
      signs of ovulation. The remaining sows from nonsuperovulated and superovulated
      groups were all pregnant, with no differences in fertilization rates among
      groups. The number of CLs and viable embryos was higher (P < 0.05) in the
      superovulated groups compared with the controls and increased (P < 0.05) with
      increasing doses of eCG. There were no differences among groups in the number of
      oocytes and/or degenerated embryos. The number of transferable embryos (morulae
      and unhatched blastocysts) obtained in pregnant sows was higher (P < 0.05) in the
      superovulated groups than in the control group. In all groups, there was a
      significant correlation between the number of CLs and the number of viable and
      transferable embryos, but the number of CLs and the number of oocytes and/or
      degenerated embryos were not correlated. A total of 46 NsDU ETs were performed in
      nonhormonally treated recipient sows, with embryos (30 embryos per transfer)
      recovered from the 1000-IU eCG, 1500-IU eCG, and control groups. In total,
      pregnancy and farrowing rates were 75.1% and 73.2%, respectively, with a litter
      size of 9.4 +/- 0.6 piglets born, of which 8.8 +/- 0.5 were born alive. There
      were no differences for any of the reproductive parameters evaluated among
      groups. In conclusion, our results demonstrated the efficiency of eCG
      superovulation treatments in decreasing the donor-to-recipient ratio. Compared
      with nonsuperovulated sows, the number of transferable embryos was increased in
      superovulated sows without affecting their quality and in vivo capacity to
      develop to term after transfer. The results from this study also demonstrate the
      effectiveness of the NsDU ET procedure used, making possible the commercial use
      of ET technology by the pig industry. 

PMID- 24462300
TI  - The reliability of routine clinical post-processing software in assessing
      potential diffusion-weighted MRI "biomarkers" in brain metastases.
AB  - BACKGROUND AND PURPOSE: Diffusion MRI characteristics have been used as
      biomarkers to guide prognosis in cerebral pathologies including brain metastases.
      The measurement of ADC is often described poorly in clinical and research studies
      with little detail given to the practical considerations of where to place ROIs,
      which post processing software package to use and how reproducible the resulting
      metrics will be. METHOD: We investigated a series of 12 patients with brain
      metastases and preoperative DWI. Three post processing platforms were used. ROI
      were placed over the tumour, peritumoural region and across the brain-tumour
      interface. These recordings were made by a neurosurgeon and a neuroradiologist.
      Inter-intra-observer variability was assessed using Bland-Altman analysis. An
      exploratory analysis of DWI with overall survival and tumour type was made.
      RESULTS: There was excellent correlation between the software packages used for
      all measures including assessing the whole tumour, selective regions with lowest
      ADC, the change of ADC across the brain-tumour interface and the relation of the
      tumour ADC to peritumoural regions and the normal white matter. There was no
      significant inter- or intra-observer variability for repeated readings. There
      were significant differences in the mean values obtained using different
      methodologies and different metrics had differing relationships to overall
      survival and primary tumour of origin. CONCLUSION: Diffusion weighted MRI metrics
      offer promise as potential non-invasive biomarkers in brain metastases and a
      variety of metrics have been shown to be reliably measured using differing
      platforms and observers.

PMID- 24462301
TI  - The combined effect of hypertension and type 2 diabetes mellitus on aortic
      stiffness and endothelial dysfunction: an integrated study with high-resolution
      MRI.
AB  - PURPOSE: The purpose of this study was to investigate the combined effect of
      hypertension and type 2 diabetes mellitus (DM2) on aortic stiffness and
      endothelial dysfunction by using an integrated MRI approach. MATERIALS AND
      METHODS: A total of 31 non-hypertensive DM2 patients and 31 hypertensive DM2
      patients underwent 3.0-T MRI. Aortic distensibility (AD), pulse wave velocity
      (PWV) and brachial artery flow-mediated dilation (FMD) were assessed. Student's t
      test, Mann-Whitney U test, chi-squared test, Pearson correlation analysis, and
      univariable and multiple linear regression analyses were used for statistical
      analyses. RESULTS: The hypertensive patients showed lower AD at multiple levels
      (ascending aorta [AA]: 2.07+/-0.98*10(-3)mm Hg(-1) vs. 3.21+/-1.70*10(-3)mm Hg(
      1), p<0.01; proximal thoracic descending aorta [PDA]: 2.58+/-0.72*10(-3)mm Hg(-1)
      vs. 3.58+/-1.47*10(-3)mm Hg(-1), p<0.01; distal descending aorta [DDA]: 3.11+/
      1.84*10(-3)mm Hg(-1) vs. 4.27+/-1.75*10(-3)mm Hg(-1), p<0.01); faster PWV (7.46+/
      2.28m/s vs. 5.82+/-1.12m/s, p<0.05) and lower FMD (12.67%+/-6.49% vs. 20.66%+/
      9.7%; p<0.01). Systolic blood pressure was an independent predictor of PWV, AA
      AD, DDA-AD and FMD. FMD was statistically significantly associated with PWV (r=
      0.37, p<0.01) and AD (p<0.01). CONCLUSIONS: Hypertension has a contributive
      effect on aortic stiffness and endothelial dysfunction in DM2 patients.

PMID- 24462302
TI  - RNA metabolism in plant mitochondria.
AB  - Mitochondria are essential for the eukaryotic cell and are derived from the
      endosymbiosis of an alpha-proteobacterial ancestor. Compared to other eukaryotes,
      RNA metabolism in plant mitochondria is complex and combines bacterial-like
      traits with novel features that evolved in the host cell. These complex RNA
      processes are regulated by families of nucleus-encoded RNA-binding proteins.
      Transcription is particularly relaxed and is initiated from multiple promoters
      covering the entire genome. The variety of RNA precursors accumulating in
      mitochondria highlights the importance of post-transcriptional processes to
      determine the size and abundance of transcripts. Here we review RNA metabolism in
      plant mitochondria, from RNA transcription to translation, with a special focus
      on their unique features that are controlled by trans-factors. 

PMID- 24462304
TI  - What happens after gastric band removal without additional bariatric surgery?
AB  - BACKGROUND: The laparoscopic adjustable gastric band (LAGB) is widely used for
      the treatment of morbid obesity. Many patients benefit from this procedure
      initially, but experience complications after a few years. The treatment for many
      complications is revisional bariatric surgery. A number of patients, however,
      request only band removal without secondary bariatric surgery. The aim of this
      study was to assess the perioperative and medium term outcomes of patients who
      had their LAGB removed without secondary bariatric surgery. METHODS: Patients
      were retrospectively selected using a prospectively collected database. The LAGB
      had to be in situ for at least 1 year, and minimum postoperative follow-up had to
      be 12 months. RESULTS: Thirty-eight patients who had their LAGB laparoscopically
      removed between 2000 and 2010 were included. Median follow-up after LAGB removal
      was 3.0 (1.4 to 8.9) years. Only 2 complications (5%) and no mortality occurred
      perioperatively. In the 21 patients who did not undergo additional bariatric
      surgery, the median excess weight loss (EWL) decreased from 41% (-12% to -100%)
      at band removal to 9% (-10% to 90%), 0% (-20% to 78%), and -11% (-12% to 56%)
      after 1, 2, and 5 years, respectively. Percentage weight loss (%WL) was 17% (-54%
      to -5%), 4% (-47% to -9%), 0% (-41% to 11%), and -5% (-29% to 9%) after these
      same time intervals, respectively. After a median 2.1 (.5 to 9.9) years, 17
      patients underwent either a Roux-en-Y gastric bypass (14 patients) or a Scopinaro
      (3 patients) all because of weight regain. The current EWL and %WL in these
      patients is 67% (24% to 113%) and 30% (12% to 53%), respectively compared with 
      11% (-33% to 57%) and -4% (-14% to 34%) in patients without a secondary bariatric
      procedure (P< .001). CONCLUSION: Patients who have their LAGB removed are
      guaranteed to suffer from weight regain. It is inadvisable to only remove the
      LAGB without performing an additional bariatric procedure when deemed technically
      feasible and safe. In this study, no patient was able to maintain the weight loss
      achieved with the LAGB after its removal.

PMID- 24462303
TI  - Bone and mineral disorders after kidney transplantation: therapeutic strategies.
AB  - Mineral and bone diseases (MBD) are common in patients with chronic kidney
      disease who undergo kidney transplantation. The incidence, types and severity of
      MBD vary according to the duration of chronic kidney disease, presence of
      comorbid conditions and intake of certain medications. Moreover, multiple types
      of pathology may be responsible for MBD. After successful reversal of uremia by
      kidney transplantation, many bone and mineral disorders improve, while
      immunosuppression, other medications, and new and existing comorbidities may
      result in new or worsening MBD. Chronic kidney disease is also common after
      kidney transplantation and may impact bone and mineral disease. In this article,
      we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant
      outcomes. We also discussed the diagnostic approach; immunosuppression management
      and potential treatment of MBD in kidney transplant recipients. 

PMID- 24462305
TI  - How frequently and when do patients undergo cholecystectomy after bariatric
      surgery?
AB  - BACKGROUND: Rapid weight loss after bariatric surgery is associated with
      gallstone formation, and cholecystectomy is required in up to 15% of patients.
      Prophylactic cholecystectomy or prophylactic ursodiol administration in the
      postoperative period have been suggested to address this problem. The objectives
      of this study were to investigate the frequency and timing of cholecystectomies
      after bariatric surgery and to determine the associated risk factors in patients
      who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic
      adjustable gastric band (LAGB), or laparoscopic sleeve gastrectomy (LSG).
      METHODS: Data prospectively collected in an institutional database were analyzed.
      Differences among the 3 procedures and the effects of ursodiol administration,
      patient demographic characteristics, postoperative weight loss, and individual
      surgeon practices on cholecystectomy rates were examined. Survival analysis and
      proportional hazard models were used. RESULTS: Of 1398 patients, 109 (7.8%)
      underwent cholecystectomy with a median follow-up of 49 (range 12-103) months.
      Cholecystectomy frequency was 10.6% after LRYGB, significantly higher than 2.9%
      after LAGB (P < .001), and 3.5% after LSG (P = .004). The frequency was highest
      within the first 6 months (3.7%), but declined over time to < 1% per year after 3
      years. Ursodiol administration did not affect cholecystectomy rates (P = .97),
      and significant intersurgeon variability was noted. Excess weight loss (EWL)>25%
      within the first 3 months was the strongest predictor of postoperative
      cholecystectomy (P<.001). Cox hazards model revealed 1.25 odds ratio per 10% EWL
      within 3 months, and odds ratio .77 per decade of life. In addition, white
      patients had 1.45 times higher cholecystectomy rates than did black patients.
      Preoperative body mass index, gender, and surgeon did not affect cholecystectomy
      rates. CONCLUSION: Bariatric surgery is associated with a low frequency of
      postoperative cholecystectomy, which is highest early after surgery and mainly
      determined by the amount of EWL within the first 3 months. The results of the
      present study do not support routine prophylactic cholecystectomy at the time of
      bariatric surgery in asymptomatic patients.

PMID- 24462306
TI  - Long-term multiple intragastric balloon treatment--a new strategy to treat morbid
      obese patients refusing surgery: prospective 6-year follow-up study.
AB  - BACKGROUND: Morbid obesity is an increasing health problem. Dietary intervention
      often fails in the medium to long term, and surgery is the gold standard.
      Intragastric balloon is a valuable treatment in the short-term, and multiple
      balloon treatment has been shown to be effective in the medium term. The aim of
      this study was to investigate the efficacy of multiple balloon treatment in the
      long-term (6 years) in terms of weight loss, influence on co-morbidities, and
      quality of life in patients refusing surgery. METHODS: Eighty-three patients with
      body mass index (BMI)>40, good candidates for surgery but refusing it, were
      enrolled in a clinical treatment protocol involving multiple intragastric balloon
      placement. After removing the first balloon, a second balloon was placed when the
      patients had regained >= 50% of the weight loss achieved with previous balloon.
      Weight, co-morbidities parameters, and quality of life test were recorded during
      a follow-up of 72 months. RESULTS: All patients experienced a second balloon
      placement; 22.2% had a third device placed and 1 patient had a fourth device
      placed. At 76 months follow-up, mean BMI was 37.6 kg/m(2) (P < .001); weight
      cycling periods were observed. Significant difference was recorded in the
      presence of co-morbidities at baseline (80% of the patients) and follow-up (30%)
      (P = .02). Quality of life test in the follow-up indicated better scores than
      those at baseline (P < . .001). CONCLUSION: Despite the weight cycling, in
      patients refusing surgery, multiple intragastric balloon is the recommended
      treatment, allowing the patients to achieve a good weight loss, better control of
      co-morbidities, and better quality of life than at baseline.

PMID- 24462307
TI  - Hyperammonemic encephalopathy complicating bariatric surgery: a case study and
      review of the literature.

PMID- 24462308
TI  - Outcomes of laparoscopic proximal gastrectomy with esophagojejunal reconstruction
      for chronic staple line disruption after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Sleeve gastrectomy is now a frequently performed bariatric procedure
      for severely obese patients and may have the lowest frequency of short-term or
      long-term complications. The aim of this study is to describe our experience in
      managing chronic proximal leaks with a proximal gastrectomy and Roux-en-Y
      esophagojejunostomy (PGEJ). METHODS: A retrospective review was performed of all
      patients having proximal chronic staple-line disruptions (CSLD) after undergoing
      laparoscopic sleeve gastrectomy. RESULTS: Fifteen patients had proximal CSLD and
      were treated with PGEJ. There was 1 (6.6%) releak in this group, which resolved
      with nonoperative treatment. Other postoperative morbidities in this series
      included partial small bowel obstruction (n = 1) and subhepatic bile collection
      (n = 1), both of which resolved without operative intervention. CONCLUSION: PGEJ
      appears to be a safe and effective procedure for chronic staple-line disruptions
      after sleeve gastrectomy.

PMID- 24462309
TI  - Comment on: Roux-en-Y gastric bypass increases hepatic and peripheral insulin
      sensitivity in rats with type 2 diabetes mellitus.

PMID- 24462310
TI  - Bariatric surgery: a safe and effective conduit to cardiac transplantation.
AB  - BACKGROUND: Obesity and obesity-related co-morbidities, including advanced heart
      failure, are epidemic. Some of these patients will progress to require cardiac
      allografts as the only means of long-term survival. Unfortunately, without
      adequate weight loss, they may never be deemed acceptable transplant candidates.
      Often surgical weight loss may be the only effective and durable option for these
      complex patients. The objective of this study was to assess whether bariatric
      surgery is feasible and safe in patients with severe heart failure, which in
      turn, after adequate weight loss, would allow these patients to be listed for a
      heart transplant. METHODS: Four patients who underwent bariatric procedures, such
      as laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve
      gastrectomy (SG), for the purpose of attaining adequate weight loss with the goal
      to improve their eligibility for orthotopic heart transplants are presented.
      RESULTS: All patients did well around the time of surgery, and 3 of the 4
      progressed to receiving a heart transplant. The fourth patient will be listed
      pending attaining adequate weight loss. CONCLUSION: Bariatric surgery may be an
      important bridge to transplantation for morbidly obese patients with severe heart
      failure. With the appropriate infrastructure, bariatric surgery is a feasible and
      effective weight loss method in this population.

PMID- 24462312
TI  - Fasting glycemia: a good predictor of weight loss after RYGB.
AB  - BACKGROUND: Preoperative prediction of weight loss after Roux-en-Y gastric bypass
      (RYGB) could help surgeons in managing surgical lists and patients' expectations.
      The objective of this study was to understand if preoperative metabolic control
      might improve surgical results. METHODS: Prospective cohort of 163 consecutive
      patients who underwent RYGB with at least 1 year of follow-up. RESULTS: Most
      patients were female (90.2%), with a mean age of 38 (19-60) and a BMI of 46.0
      (34.3-59.9) kg/m(2). After 12 months, the mean body mass index (BMI) was 29.7
      kg/m(2) (21.5-39.9) with a corresponding percentage of excess weight lost (%EWL)
      of 78.8% and a percentage of weight loss (%WL) of 35.1%. Patients with the
      highest preoperative fasting blood glucose (FBG) were older (42 versus 36;
      P<.001); were more likely to have type 2 diabetes (T2 DM, 40% versus 6.8%;
      P<.001) and metabolic syndrome (89% versus 25%; P<.001), had a slightly higher
      BMI (30.8 versus 29.3 kg/m(2); P = .03), and had achieved a significantly lower
      %EWL and %WL at 12 months (72.5% versus 81.2%; P = .004; 33.2 versus 35.9%; P =
      .03, respectively). We observed a dose-response effect with increasing FBG (<85
      mg/dL, 85-100 mg/dL, and >= 100 mg/dL, respectively), with 83.5%, 80.0%, and
      72.5% (P = .009) of %EWL at 12 months. By multivariate logistic regression,
      initial BMI and FBG>100, were the only variables related (inversely) with the
      probability of achieving a %EWL>80 or %WL>35. This effect was not detected in
      patients receiving oral antidiabetic medications. CONCLUSION: Higher preoperative
      FBG is independently related to a poorer weight loss 12 months after RYGB; this
      suggests the need to offer earlier surgical intervention for severely obese
      patients with impairment of glucose metabolism. The potential for less weight
      loss in patients with a higher FBG should not discourage RYGB, given the
      significant metabolic improvement after surgery.

PMID- 24462311
TI  - Laparoscopic sleeve gastrectomy as a revisional procedure for failed laparoscopic
      gastric banding with a "2-step approach": a multicenter study.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been proposed as an
      alternative revisional procedure for failed/complicated gastric banding. This is
      a retrospective cohort study of a prospectively maintained database of revisional
      LSG after band removal for insufficient weight loss and/or band-related
      complications, using a 2-step approach. The outcomes were compared with a control
      group of primary LSG. The study was conducted at a university hospital (Sapienza
      University of Rome-Polo Pontino, Icot, Latina, Italy) and 2 community general
      hospitals (Hospital Andosilla Civita Castellana, Viterbo, Italy and Hospital
      Villa D'Agri, Potenza, Italy). METHODS: A total of 76 revisional LSG procedures
      was recorded; a control group of 279 LSG patients was selected. The primary
      endpoint was to compare the perioperative complication rate between the
      revisional versus the control group. Secondary endpoints were operative time,
      conversion rate, postoperative length of stay and percentage excess weight loss
      (%EWL) at 6, 12, and 24 months. RESULTS: The indications for band removal were
      inadequate weight loss (47 patients), slippage (10 patients), erosion (7
      patients), and pouch dilation (12 patients). All procedures were completed
      laparoscopically. The median operative time was 78 minutes for the revision LSG
      and 65 minutes for the control LSG (P<.05). In the revision group, the overall
      complication rate was 17.1%, and the median postoperative length of stay was 4
      days; in the control group, the overall complication rate was 10.7%, and the
      median postoperative length of stay was 3. No complications requiring reoperation
      or readmission occurred in the revision group. In the control group, there were 5
      cases of major complications. All the patients completed the follow-up. A total
      of 56 patients in the revision group and 184 patients in the control group were
      followed-up for at least 24 months. The %EWL at 6, 12, and 24 months was 46.5%,
      66.4%, and 78.5%, respectively, in the revision group, and 49.8%, 78.2%, and 78%,
      respectively, in the control group. CONCLUSION: Results confirmed that LSG,
      performed in 2 steps, is an effective revision procedure for failed or
      complicated laparoscopic adjustable gastric banding with good perioperative
      outcomes and 2-year weight loss.

PMID- 24462313
TI  - Management and treatment outcomes of marginal ulcers after Roux-en-Y gastric
      bypass at a single high volume bariatric center.
AB  - BACKGROUND: Marginal ulceration (MU) is one of the most common complications
      after Roux-en-Y gastric bypass (RYGB). However, the rate of MU varies from 1% to
      16% of RYGB patients and predisposing factors remain unclear. The aim of this
      study is to describe frequency, management, and outcomes of treatment in patients
      with MU after laparoscopic RYGB. METHODS: Between January 2004 and December 2012,
      a total of 2,535 patients underwent laparoscopic RYGB at our institution.
      Patients were routinely placed on proton pump inhibitors (PPI) for 90 days after
      the procedure. A total of 59 (2.3%) patients presented with MU. A retrospective
      review of a prospectively collected database was performed for all patients.
      RESULTS: Patients with MU presented with abdominal pain (n = 35), nausea/vomiting
      (n = 9), anemia (n = 5), hematemesis (n = 5), and dysphagia (n = 5) as chief
      complaints. Diagnosis was made at a mean period of 15.2 +/- 17.4 months (range, 1
      64) after the laparoscopic RYGB. Of these patients, 26 (44.1%) required
      reoperations including 12 (20.3%) with perforated ulcers. Urgent operation was
      required in 14 (23.7%) patients due to perforation or active bleeding, and
      elective operation was performed in 10 (16.9%) patients for chronic and
      refractory MU or gastrogastric fistula. One (1.7%) patient developed recurrent MU
      after the revision and had another revision of the anastomosis. One (1.7%)
      patient underwent reversal of gastric bypass after the revision due to
      malnutrition and recurrent ulcers. All patients did well at a mean follow up of
      28.9 +/- 21.7 months (range, 1-78 mo). CONCLUSION: Despite the use of routine
      PPI, the incidence of MU was not insignificant. A significant portion of patients
      required surgical treatment. Perforations can be effectively managed by
      oversewing of the ulcer.

PMID- 24462314
TI  - Comment on: Is laparoscopic single-stage biliopancreatic diversion with duodenal
      switch safe in super morbidly obese patients?

PMID- 24462316
TI  - Google Trends: is it a real tool to predict the future of bariatric surgery or
      merely a marketing landmine?

PMID- 24462315
TI  - Banded Roux-en-Y gastric bypass for the treatment of morbid obesity.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most effective
      treatment for morbid obesity. The additional benefit of placing a nonadjustable
      band around the pouch remains to be determined. The objective of this study was
      to compare outcomes between banded and nonbanded LRYGB patients in a single
      bariatric center. METHODS: A matched cohort analysis was performed between
      patients who had undergone banded and nonbanded (standard) LRYGB. In the banded
      bypass cohort, an 8 F, 6.5 cm silastic ring was placed around the proximal
      gastric pouch. Both cohorts were matched for age, body mass index (BMI), and
      anastomotic technique. Endpoints included percentage excess weight loss (%EWL),
      postoperative morbidity, and band-related complications. RESULTS: Between January
      2007 and July 2010, 134 banded LRYGB were performed (55% female, mean age 45
      years). They were compared with a matched cohort of 134 concurrent nonbanded
      LRYGB patients (67% female, mean age 45.4 years). Mean preoperative BMI was 54.6
      and 52.8 kg/m(2), respectively (P = .084). At 24 months postoperatively, the
      average %EWL was 58.6% in banded bypass patients and 51.4% in the nonbanded group
      (P = .015). The difference in EWL was more pronounced in super-obese patients
      than in those with BMI<50 (among super-obese, 57.5% versus 47.6%, P = .003; among
      those with BMI<50, 62.9% versus 57.9%, P = .406]. There was no difference in
      early (19.4% versus 19.4%) or late complications (10.4% versus 13.4%, P = .451)
      between banded and nonbanded LRYGB patients. CONCLUSION: Banding the pouch during
      LRYGB can be performed safely and may provide better weight loss, particularly in
      super-obese patients. Further prospective and long-term comparative studies of
      this technique are warranted.

PMID- 24462317
TI  - Serum ionized magnesium in diabetic older persons.
AB  - OBJECTIVE: Several alterations of magnesium metabolism have been associated with
      type 2 diabetes pathophysiology, a condition particularly frequent in older
      persons. We aimed to evaluate serum total (Mg-tot) and serum ionized magnesium
      (Mg-ion) in older persons with type 2 diabetes in order to explore clinically
      applicable methods for the detection of magnesium deficit. MATERIAL/METHODS: Mg
      tot and Mg-ion were measured in 105 fasting subjects with type 2 diabetes (mean
      age: 71.1+/-0.8 years; M/F: 45/60) and in 100 age-matched non-diabetic control
      persons (mean age: 72.2+/-0.8 years; M/F: 42/58). RESULTS: Mg-ion concentrations
      were significantly lower in diabetic persons compared with controls (0.49+/-0.05
      mmol/L vs. 0.55+/-0.05 mmol/L; p<0.001). Mg-tot was also slightly but
      significantly lower in diabetic patients (0.82+/-0.007 mmol/L vs. 0.84+/-0.006
      mmol/L; p<0.05). There was an almost complete overlap in the values of Mg-tot in
      older diabetic patients and controls; conversely, 44.8% of diabetic patients had
      Mg-ion values below 0.47 mmol/L, while none of the controls did. After adjustment
      for age, sex, BMI, and triglycerides, Mg-tot was significantly associated with
      FBG in all the participants (p<0.05) and Mg-ion was significantly associated with
      FBG in all the participants (p<0.01) and with HbA1c in diabetic participants
      (p<0.001). CONCLUSIONS: Alterations of magnesium serum concentrations are common
      in type 2 diabetic older adults; Mg-ion evaluation may help to identify
      subclinical magnesium depletion (i.e. in patients with normal Mg-tot); the close
      independent associations of Mg-tot and Mg-ion with FBG and with HbA1c reinforce
      the possible link between magnesium homeostasis and altered glucose metabolism.

PMID- 24462318
TI  - Doping control, providing whereabouts and the importance of privacy for elite
      athletes.
AB  - BACKGROUND: To improve anti-doping efforts in sports, the World Anti-Doping
      Agency (WADA) introduced the World Anti-Doping Program, in which (among others)
      regulations for providing athletes' whereabouts are described. Because the
      effectiveness and efficiency of this system depends on the co-operation and
      compliance of athletes, the perspective of elite athletes is important. This
      paper answers the following research questions: What is the perspective of Dutch
      elite athletes on the current whereabouts system in general and how important is
      their privacy in providing whereabouts in particular? In addition, this study
      explores how far the whereabouts system can be developed in the future. Are
      athletes willing to accept greater invasions of their privacy in order to reduce
      administrative effort and whereabouts failures? METHOD: A structured
      questionnaire was completed by 129 Dutch elite athletes registered in the
      national and/or international testing pool. RESULTS: The results of this study
      indicate widespread dissatisfaction with the whereabouts system. Most respondents
      support anti-doping testing in general, but many athletes feel that WADA's
      whereabouts system is unacceptable in several respects. In terms of physical
      privacy, there was a great dissatisfaction. Nearly half of the athletes felt that
      the '1-hour time slot' limits their freedom, but on the other hand, most athletes
      disagreed with the statement that the distinction between their sport and private
      life is disturbed. For almost one in three respondents, the whereabouts system
      has a negative influence on the pleasure they experience in being an elite
      athlete. In terms of informational privacy, almost all athletes had confidence in
      the confidential treatment of their whereabouts information. Almost all athletes
      would accept giving their phone number to Doping Control Officials, but only half
      of the athletes would accept sharing their location on their mobile phone.
      Furthermore, almost two in ten of the athletes would accept wearing a permanent
      wrist or ankle bracelet or accept being implanted with a GPS chip in order to
      facilitate future anti-doping testing. CONCLUSION: The current whereabouts system
      needs to be improved in order to increase athletes' satisfaction with the anti
      doping rules. The athletes themselves need to be engaged in this process. The
      results of this study indicate that a majority of the athletes are not likely to
      accept a greater violation of their privacy than the current whereabouts
      regulations already entail.

PMID- 24462319
TI  - [Transduction].

PMID- 24462320
TI  - [An unusual paranasal dermatologic lesion in a child. Acacia thorn].

PMID- 24462321
TI  - 6-Mercaptopurine/Azathioprine remains an important contributor in managing
      Crohn's disease.
AB  - Two large studies concluded that AZA started early after diagnosis of Crohn's
      disease have no late maintenance value. This is contrary to previous studies on
      6MP for Crohn's disease and could lead to negating the value of two of the few
      drugs that have been proven successful. We here outline the many reasons why 6MP
      remains a valuable drug in the treatment of Crohn's disease.

PMID- 24462323
TI  - The abridged patient-generated subjective global assessment is a useful tool for
      early detection and characterization of cancer cachexia.
AB  - Cancer cachexia (CC) is a syndrome characterized by wasting of lean body mass and
      fat, often driven by decreased food intake, hypermetabolism, and inflammation
      resulting in decreased lifespan and quality of life. Classification of cancer
      cachexia has improved, but few clinically relevant diagnostic tools exist for its
      early identification and characterization. The abridged Patient-Generated
      Subjective Global Assessment (aPG-SGA) is a modification of the original Patient
      Generated Subjective Global Assessment, and consists of a four-part questionnaire
      that scores patients' weight history, food intake, appetite, and performance
      status. The purpose of this study was to determine whether the aPG-SGA is
      associated with both features and clinical sequelae of cancer cachexia. In this
      prospective cohort study, 207 advanced lung and gastrointestinal cancer patients
      completed the following tests: aPG-SGA, Edmonton Symptom Assessment System,
      handgrip strength, a complete blood count, albumin, apolipoprotein A and B, and C
      reactive protein. Ninety-four participants with good performance status as
      assessed by the Eastern Cooperative Oncology Group Performance Status completed
      additional questionnaires and underwent body composition testing. Of these, 68
      patients tested for quadriceps strength and completed a 3-day food recall.
      Multivariable regression models revealed that higher aPG-SGA scores (>=9 vs 0 to
      1) are significantly associated (P<0.05) with the following: unfavorable
      biological markers of cancer cachexia, such as higher white blood cell counts
      (10.0 vs 6.7*10(9)/L; lower hemoglobin (115.6 vs 127.7 g/L), elevated C-reactive
      protein (42.7 vs 18.2 mg/L [406.7 vs 173.3 nmol/L]); decreased anthropometric and
      physical measures, such as body mass index (22.5 vs 27.1); fat mass (14.4 vs 26.0
      kg), handgrip (24.7 vs 34.9 kg) and leg strength; an average 12% greater length
      of hospital stay; a dose reduction in chemotherapy; and increased mortality.
      Given its association with the main features of cancer cachexia and its ease of
      use, the aPG-SGA appears to be a useful tool for detecting and predicting
      outcomes of cancer cachexia. Additional research is required to determine what
      impact the aPG-SGA has on quality of care when used in the clinical setting.

PMID- 24462322
TI  - Appropriateness and long-term discontinuation rate of biological therapies in
      ulcerative colitis.
AB  - BACKGROUND: Anti-TNFalpha agents are commonly used for ulcerative colitis (UC)
      therapy in the event of non-response to conventional strategies or as colon
      salvaging therapy. The objectives were to assess the appropriateness of
      biological therapies for UC patients and to study treatment discontinuation over
      time, according to appropriateness of treatment, as a measure of outcome.
      METHODS: We selected adult ulcerative colitis patients from the Swiss IBD cohort
      who had been treated with anti-TNFalpha agents. Appropriateness of the first-line
      anti-TNFalpha treatment was assessed using detailed criteria developed during the
      European Panel on the Appropriateness of Therapy for UC. Treatment
      discontinuation as an outcome was assessed for categories of appropriateness.
      RESULTS: Appropriateness of the first-line biological treatment was determined in
      186 UC patients. For 64% of them, this treatment was considered appropriate.
      During follow-up, 37% of all patients discontinued biological treatment, 17%
      specifically because of failure. Time-to-failure of treatment was significantly
      different among patients on an appropriate biological treatment compared to those
      for whom the treatment was considered not appropriate (p=0.0007). Discontinuation
      rate after 2years was 26% compared to 54% between those two groups. Patients on
      inappropriate biological treatment were more likely to have severe disease,
      concomitant steroids and/or immunomodulators. They were also consistently more
      likely to suffer a failure of efficacy and to stop therapy during follow-up.
      CONCLUSION: Appropriateness of first-line anti-TNFalpha therapy results in a
      greater likelihood of continuing with the therapy. In situations where biological
      treatment is uncertain or inappropriate, physicians should consider other options
      instead of prescribing anti-TNFalpha agents.

PMID- 24462324
TI  - Numerical modelling of the physical factors that affect mass transport in the
      vasculature at early time periods.
AB  - Coronary artery disease results in blockages or narrowing of the artery lumen.
      Drug eluting stents were developed to replace bare metal stents in an effort to
      combat re-blocking of the lumen. A key element in determining the therapeutic
      success of a drug eluting stent is an in-depth understanding of the physical
      factors that affect mass transport of the drug into the arterial wall, over early
      time periods. The numerical models developed within this study focus on assessing
      the influence of a host of physical factors that either facilitate or impede
      therapeutic drug delivery into the arterial wall from the unit cell of an
      idealised stent. This study demonstrates that model reduction strategies to 2D
      and 1D can still adequately represent a 3D curved arterial wall and strut polymer
      coating, respectively, using an idealistic stent geometry. It was shown that the
      level of strut compression can have a significant impact on therapeutic drug
      delivery in the arterial wall. 

PMID- 24462325
TI  - [Intravenous paracetamol in the neonate and infant less than 10kg].

PMID- 24462326
TI  - Assessment of sexual dysfunction and determination of its risk factors in the
      Republic of Korea.
AB  - OBJECTIVE: To assess sexual function among women via self-evaluation of female
      sexual dysfunction (FSD) and to determine risk factors for FSD among Korean
      women. METHODS: A preliminary questionnaire-based study in Ansan, Korea, enrolled
      935 women between January and December 2010. Participants completed the Female
      Sexual Function Index and a self-administered survey. Participants were divided
      into 2 groups: in the recognized group (RG), women were aware of their sexual
      problems; in the unrecognized group (URG), women were not. RESULTS: The
      prevalence of FSD was 46.1% (n=431). The prevalence of recognized FSD was 21.5%
      (n=201), whereas that of unrecognized FSD was 24.6% (n=230) Younger women showed
      a significantly more positive attitude toward sex compared with older individuals
      (P<0.001). Sexual desire, sexual arousal, dyspareunia, lubrication, and sexual
      satisfaction were factors of sexual dysfunction in the RG. In the URG, sexual
      arousal, sexual desire, orgasm, dyspareunia, and sexual satisfaction were
      identified as significant factors. CONCLUSION: Women in the RG had positive
      attitudes toward sex, whereas those in the URG had negative attitudes. Women who
      were unsatisfied with their sexual life did not express a need for treatment. The
      sociocultural background of Korean women should be considered in the diagnosis
      and treatment of FSD.

PMID- 24462327
TI  - Cerclage retention versus removal following preterm premature rupture of
      membranes and association with amniotic fluid markers.
AB  - OBJECTIVE: To evaluate whether amniotic fluid markers can aid the decision of
      whether to retain or remove a cervical cerclage after preterm premature rupture
      of membranes (PPROM). METHODS: A retrospective cohort study included pregnancies
      involving PPROM after diagnostic amniocentesis and cerclage placement. Cerclage
      was retained for more than 12 hours after PPROM in the study group (n=18); the
      comparison group comprised women who underwent immediate cerclage removal after
      PPROM (n=22). Analyses were performed using concentrations of interleukin (IL)-6,
      glucose, and white blood cells (WBCs) in the amniotic fluid to measure
      relationships with adverse outcomes. RESULTS: The latency period from PPROM to
      delivery was significantly shorter in the group that underwent immediate cerclage
      removal (P<0.005). Latency periods of more than 48 hours (P<0.001) and more than
      7 days (P<0.01), and chorioamnionitis (P<0.05) were associated with cerclage
      retention. Neonatal outcomes were not significantly different between the study
      group and the comparison group. However, elevated IL-6 levels were associated
      with cumulative neonatal morbidity (P<0.05). Low IL-6 (P<0.001) and WBC (P<0.05)
      levels were significantly associated with a latency period of more than 7 days.
      CONCLUSION: Amniotic fluid levels of IL-6 and WBCs may be of clinical value for
      individualizing the management of patients with PPROM after cerclage.

PMID- 24462328
TI  - WHO guidelines on fluid resuscitation in children with shock.

PMID- 24462329
TI  - pKa determination by 1H NMR spectroscopy - an old methodology revisited.
AB  - pKa values of acids and protonated bases have an essential impact on organic
      synthesis, medicinal chemistry, and material and food sciences. In drug discovery
      and development, they are of utmost importance for the prediction of
      pharmacokinetic and pharmacodynamic properties. To date, various methods for the
      determination of pKa values are available, including UV-spectroscopic,
      potentiometric, and capillary electrophoretic techniques. An additional option is
      provided by nuclear magnetic resonance (NMR) spectroscopy. The underlying
      principle is the alteration of chemical shifts of NMR-active nuclei (e.g., (13)C
      and (1)H) depending on the protonation state of adjacent acidic or basic sites.
      When these chemical shifts are plotted against the pH, the inflection point of
      the resulting sigmoidal curve defines the pKa value. Although pKa determinations
      by (1)H NMR spectroscopy are reported for numerous cases, the potential of this
      approach is not yet fully evaluated. We therefore revisited this method with a
      diverse set of test compounds covering a broad range of pKa values (pKa 0.9-13.8)
      and made a comparison with four commonly used approaches. The methodology
      revealed excellent correlations (R(2)=0.99 and 0.97) with electropotentiometric
      and UV spectroscopic methods. Moreover, the comparison with in silico results
      (Epik and Marvin) also showed high correlations (R(2)=0.92 and 0.94), further
      confirming the reliability and utility of this approach.

PMID- 24462330
TI  - How to teach emergency procedural skills in an outdoor environment using low
      fidelity simulation.
AB  - Teaching emergency procedural skills in a wilderness setting can be logistically
      challenging. To teach these skills as part of a wilderness medicine elective for
      medical students, we designed an outdoor simulation session with low-fidelity
      models. The session involved 6 stations in which procedural skills were taught
      using homemade low-fidelity simulators. At each station, the students encountered
      a "victim," who required an emergency procedure that was performed using the low
      fidelity model. The models are easy and inexpensive to construct, and their
      design and implementation in the session is described here. Using low-fidelity
      simulation models in an outdoor setting is an effective teaching tool for
      emergency wilderness medicine procedures and can easily be reproduced in future
      wilderness medicine courses. 

PMID- 24462331
TI  - Use of the visual range of detection to estimate effective sweep width for land
      search and rescue based on 10 detection experiments in North America.
AB  - OBJECTIVE: Standard-of-practice search management requires that the probability
      of detection (POD) be determined for each search resource after a task. To
      calculate the POD, a detection index (W) is obtained by field experiments.
      Because of the complexities of the land environment, search planners need a way
      to estimate the value of W without conducting formal experiments. We demonstrate
      a robust empirical correlation between detection range (Rd) and W, and argue that
      Rd may reliably be used as a quick field estimate for W. METHODS: We obtained the
      average maximum detection range (AMDR), Rd, and W values from 10 detection
      experiments conducted throughout North America. We measured the correlation
      between Rd and W, and tested whether the apparent relationship between W and Rd
      was statistically significant. RESULTS: On average we found W ~ 1.645 * Rd with a
      strong correlation (R(2) = .827). The high-visibility class had W ~ 1.773 * Rd
      (also R(2) = .867), the medium-visibility class had W ~ 1.556 * Rd (R(2) = .560),
      and the low-visibility had a correction factor of 1.135 (R(2) = .319) for Rd to
      W. Using analysis of variance and post hoc testing, only the high- and low
      visibility classes were significantly different from each other (P < .01). We
      also found a high correlation between the AMDR and Rd (R(2) = .9974).
      CONCLUSIONS: Although additional experiments are required for the medium- and low
      visibility search objects and in the dry-domain ecoregion, we suggest search
      planners use the following correction factors to convert field-measured Rd to an
      estimate of the effective sweep width (W): high-visibility W = 1.8 * Rd; medium
      visibility W = 1.6 * Rd; and low-visibility W = 1.1 * Rd.

PMID- 24462332
TI  - Wilderness Medical Society practice guidelines for the treatment of acute pain in
      remote environments.
AB  - The Wilderness Medical Society convened an expert panel to develop evidence-based
      guidelines for the management of pain in austere environments. Recommendations
      are graded based on the quality of supporting evidence as defined by criteria put
      forth by the American College of Chest Physicians. 

PMID- 24462333
TI  - Induction gemcitabine plus concurrent gemcitabine and radiotherapy for locally
      advanced unresectable or resected pancreatic cancer.
AB  - AIMS: To determine the efficacy of induction gemcitabine followed by biweekly
      gemcitabine concurrent with radiotherapy for locally advanced pancreatic cancer.
      MATERIALS AND METHODS: Between March 2001 and August 2009, 90 patients with
      unresectable (78) or resected (12) pancreatic cancer were treated with a standard
      treatment policy of induction gemcitabine (seven doses of weekly gemcitabine at
      1000 mg/m(2)) followed by concurrent radiotherapy (52.5 Gy) and biweekly
      gemcitabine (40 mg/m(2)). RESULTS: After induction gemcitabine, 17.8% of patients
      did not proceed to chemoradiotherapy, due to either disease progression,
      performance status deterioration or gemcitabine toxicity. Of the patients who
      received chemoradiotherapy, 68.9% completed the course of 52.5 Gy, whereas 79.7%
      received more than 45 Gy. Chemoradiotherapy was stopped early due to treatment
      toxicity in 22.9% of patients. On intention to treat analysis, the median overall
      survival was 12.7 months in the locally advanced group and 18.2 months in the
      resected group. On multivariate analysis for the unresectable patients, a larger
      gross tumour volume was a significant poor prognostic factor for overall survival
      and local progression-free survival. CONCLUSION: This large series confirms, in a
      standard practice setting, similar efficacy and tolerability of treatment as
      previously reported in our phase I-II study. The benefit to patients with a gross
      tumour volume >48 cm(3) may be limited.

PMID- 24462334
TI  - Sleep, synaptic connectivity, and hippocampal memory during early development.
AB  - Sleep, specifically sleep slow-wave activity (SWA), contributes to global
      synaptic homeostasis in neocortical networks by downscaling synaptic connections
      that were potentiated during prior wakefulness. In parallel, SWA supports the
      consolidation of hippocampus-dependent episodic memory, a process linked to local
      increases in synaptic connectivity. During development, both SWA and episodic
      memory show parallel time courses: distinct SWA and capabilities to form episodic
      memory become established during infancy and then profoundly increase across
      childhood until puberty. We propose that the parallel increases across childhood
      reflect an imbalance in the underlying regulation of synaptic connectivity during
      sleep; although memory consolidation favoring synaptic potentiation is enhanced,
      global synaptic downscaling during sleep SWA does not attain complete recovery of
      homeostatic baseline levels. 

PMID- 24462335
TI  - Serotonin-1A receptor CC genotype is associated with persistent depression
      related to interferon-alpha in hepatitis C patients.
AB  - OBJECTIVE: The aim of this study is to investigate the development of depression
      during interferon-alpha (IFN-alpha) therapy and the variations in the expression
      of the serotonin receptor (5-HTR) and transporter (5-HTT) in hepatitis C
      patients. METHOD: Hepatitis C patients (n=277) were given the Mini International
      Neuropsychiatric Interview at the end of IFN-alpha therapy. Three polymorphisms
      were genotyped: the serotonin transporter repeat length polymorphic region [5-HTT
      gene-linked polymorphic region (5-HTTLPR)], as well as SNPs rs25531 and rs6295,
      located within the 5-HTTLPR and the transcriptional control region of the 5-HTR1A
      gene, respectively. RESULTS: The diagnosis of current depression, which was
      associated with IFN-alpha-related depression (P<.001), demonstrated a
      statistically significant association with the CC genotype of the 5-HTR1A gene
      (odds ratio=5.57, 95% confidence interval=1.61-19.24, P=.007). CONCLUSIONS:
      Persistent depression may represent a more specific type of IFN-alpha-related
      psychopathology. Future studies need to investigate the genetic risk factors for
      vulnerability associated with persistent depression. Limitations, such as the
      study's cross-sectional design, small sample size and retrospective assessment of
      IFN-alpha-induced depression diagnosis, must be taken into account while
      interpreting the results found in this study.

PMID- 24462336
TI  - How does antiepileptic drug induce suicidality? A case associated with
      levitracetam use.
AB  - New antiepileptic drugs have been known to increase the risk of suicide. Among
      them, levitracetam is a widely used antiepileptic drug approved as a monotherapy
      treatment for partial seizures or as an adjunctive therapy for partial, myoclonic
      and generalized tonic-clonic seizures. It has been reported that the incidence of
      suicidal ideation during treatment with levitracetam was about 0.5-0.7%, but an
      explanation regarding a mechanism by which it causes suicidality is lacking. We
      made a multifaceted approach using the Hamilton Depression Rating Score (HDRS),
      the Hamilton Anxiety Rating Score (HARS), the Beck Hopelessness Scale (BHS), the
      Barratt Impulsiveness Scale (BIS), the Beck Scale for Suicidal Ideation (BSS)
      ideation daily and the Sheehan Suicidality Tracking Scale (SSTS) weekly in a
      patient taking levitracetam who acutely developed suicidal ideation after
      starting the medication. Suicidal ideation disappeared within 5 days of
      levitracetam discontinuation. We found that decreasing HDRS and BHS scores were
      correlated with BSS and SSTS scores. On the other hand, HARS and BIS did not
      change from their baselines. Our findings suggest that suicidality induced by an
      antiepileptic drug may be related to depression rather than anxiety and
      impulsiveness. 

PMID- 24462337
TI  - Prevalence of depressive symptoms and predictors of treatment among U.S. adults
      from 2005 to 2010.
AB  - OBJECTIVES: To determine nationally representative estimates of the prevalence of
      depressive symptoms and factors associated with treatment among those with
      moderate to severe symptoms. METHODS: A cross-sectional, retrospective analysis
      of adults age>=18 years in the 2005-2010 National Health and Nutrition
      Examination Survey data who responded to the Patient Health Questionnaire (PHQ-9)
      was conducted (n=13,320). Depressive symptoms and severity were defined by PHQ-9
      scores. Depression treatment was defined as either receiving antidepressants or
      seeing a mental health professional. Multivariable logistic regression analyses
      using population weights identified factors associated with having depressive
      symptoms and receipt of any treatment. RESULTS: The prevalence of depressive
      symptoms increased from 20.92% to 25.66% over 6 years. Among patients with
      moderate to severe depression, 38.66% received treatment. Multivariable analyses
      found that being female, other Hispanic, younger age, having certain chronic
      comorbidities or previous hospitalization, no health insurance and in poverty
      status were associated with having depressive symptoms (P<.05). Among patients
      with moderate to severe depression, being female, white, younger age, having
      comorbidities (arthritis and hypertension) or previous hospitalization were
      associated with receipt of treatment (P<.05). CONCLUSIONS: The prevalence of
      depressive symptoms is high, and only a small portion of patients with moderate
      to severe depression received treatments. Treatment disparities exist and need
      improvement.

PMID- 24462338
TI  - Physicochemical and thermal characterization of nonedible oilseed residual waste
      as sustainable solid biofuel.
AB  - The present study aims to investigate the potential of nonedible oilseed Jatropha
      (Jatropha curcas) and Karanja (Pongamia pinnata) defatted residual biomasses
      (whole seed, kernel, and hull), as solid biofuel. These biomasses showed good
      carbon contents (39.8-44.5%), whereas, fewer amounts were observed for sulfur
      (0.15-0.90%), chlorine (0.64-1.76%), nitrogen (0.9-7.2%) and ash contents (4.0
      8.7%). Their volatile matter (60.23-81.6%) and calorific values (17.68-19.98
      MJ/kg) were found to be comparable to coal. FT-IR and chemical analyses supported
      the presence of good amount of cellulose, hemicellulose and lower lignin. The
      pellets prepared without any additional binder, showed better compaction ratio,
      bulk density and compressive strength. XRF analysis carried out for determination
      of slagging-fouling indices, suggested their ash deposition tendencies in
      boilers, which can be overcome significantly with the optimization of the blower
      operations and control of ash depositions. Thus, overall various chemical,
      physical properties, thermal decomposition, surface morphological studies and
      their high biofuel reactivity indicated that residual biomasses of Jatropha and
      Karanja seeds have high potential to be utilized as a solid biofuel.

PMID- 24462339
TI  - Fungal and enzymatic treatment of mature municipal landfill leachate.
AB  - The aim of our study was to evaluate biotreatability of mature municipal landfill
      leachate by using white rot fungus and its extracellular enzymes. Leachates were
      collected in one active and one closed regional municipal landfill. Both chosen
      landfills were operating for many years and the leachates generated there were
      polluted by organic and inorganic compounds. The white rot fungus Dichomitus
      squalens was able to grow in the mature leachate from the closed landfill and as
      it utilizes present organic matter as a source of carbon, the results were
      showing 60% of DOC and COD removal and decreased toxicity to the bacterium
      Aliivibrio fischeri. On the other hand, growth of the fungus was inhibited in the
      presence of the leachate from the active landfill. However, when the leachate was
      introduced to a crude enzyme filtrate containing extracellular ligninolytic
      enzymes, removal levels of COD and DOC reached 61% and 44%, respectively.
      Furthermore, the treatment led to detoxification of the leachate to the bacterium
      Aliivibrio fischeri and to reduction of toxicity (42%) to the plant Sinapis alba.
      Fungal and enzymatic treatment seems to be a promising biological approach for
      treatment of mature landfill leachates and their application should be further
      investigated. 

PMID- 24462340
TI  - Patterns of physical activity and sedentary behavior after bariatric surgery: an
      observational study.
AB  - BACKGROUND: Engaging in low levels of physical activity (PA) and accumulating
      prolonged periods of sedentary behavior (SB) during daily life have been
      associated with deleterious health outcomes. The objective of this study was to
      undertake an analysis of the way in which PA and SB were accumulated after
      bariatric surgery. METHODS: Adults 12 to 18 months after laparoscopic adjustable
      gastric banding or 6 to 18 months after laparoscopic sleeve gastrectomy wore 2
      activity monitors during the waking hours for 7 days. Anthropometric and
      demographic data were recorded. RESULTS: Data were available on 40 participants
      (30 females; median +/- interquartile range: age 46 +/- 16 years, time since
      surgery 14 +/- 8 months, body mass index 36 +/- 9 kg/m(2)). The proportion of
      waking hours spent in SB, light PA, moderate PA, and vigorous PA was 72% +/- 12%,
      22% +/- 9%, 5% +/- 3% and 0% +/- 0%, respectively. Half of the time in SB was
      accumulated in uninterrupted bouts >= 30 minutes. Almost all PA was accumulated
      in bouts<10 minutes in duration. The median daily step count was 9108 +/- 4360.
      The proportion of people who completed an average of >= 10,000 steps/d was
      similar to that reported in Western Australian adults (39% versus 32%; P = .35).
      CONCLUSION: Our sample spent>70% of time in SB, half of which was accumulated in
      uninterrupted bouts >= 30 minutes. Very little time was spent in moderate or
      vigorous PA (5%), and this was accumulated in short bouts (<10 minutes).
      Healthcare professionals should target not just overall time in SB and PA, but
      also aim to reduce prolonged periods of SB and increase sustained periods of PA.

PMID- 24462341
TI  - The usefulness of ranolazine for the treatment of refractory chronic stable
      angina pectoris as determined from a systematic review of randomized controlled
      trials.
AB  - Despite the use of traditional antianginal medications (i.e., beta blockers,
      calcium channel blockers, and nitrates) and revascularization therapies, symptoms
      of chronic stable angina pectoris (CSAP) persist in >=25% of patients. The
      objective of this systematic review was to synthesize the available evidence from
      randomized controlled trials (RCTs) of ranolazine for the treatment of CSAP. We
      systematically searched the Cochrane Register of Controlled Trials, EMBASE, and
      MEDLINE through July 2013 for RCTs comparing ranolazine with placebo or
      antianginal medications administered as part of usual care for the management of
      CSAP. End points of interest included exercise stress test performance (duration,
      time to angina, and time to ST-segment depression), frequency of angina
      attacks/week, nitroglycerin use/week, and quality of life. We identified 7 RCTs
      (n = 3,317) of patients with CSAP due to coronary artery disease. Comparators
      included placebo, amlodipine, and atenolol. All but 1 trial showed a
      statistically significant improvement in all 3 exercise stress test parameters
      with ranolazine compared with placebo. Ranolazine also reduced angina frequency
      and nitroglycerin use compared with placebo. These findings were consistent
      whether or not patients were also prescribed traditional antianginal
      pharmacotherapy. In conclusion, ranolazine reduces anginal symptoms among
      patients with symptomatic CSAP despite their use of traditional antianginal
      medications.

PMID- 24462342
TI  - Cross-country comparisons of health-care costs: the case of cancer treatment in
      the Nordic countries.
AB  - The objective of this study is to perform a cross-country comparison of cancer
      treatment costs in the Nordic countries, and to demonstrate the added value of
      decomposing documented costs in interpreting national differences. The study is
      based on individual-level data from national patient and prescription drug
      registers, and data on cancer prevalence from the NORDCAN database. Hospital
      costs were estimated on the basis of information on diagnosis-related groups
      (DRG) cost weights and national unit costs. Differences in per capita costs were
      decomposed into two stages: stage one separated the price and volume components,
      and stage two decomposed the volume component, relating the level of activity to
      service needs and availability. Differences in the per capita costs of cancer
      treatment between the Nordic countries may be as much as 30 per cent. National
      differences in the costs of treatment mirror observed differences in total health
      care costs. Differences in health care costs between countries may relate to
      different sources of variation with different policy implications. Comparisons of
      per capita spending alone can be misleading if the purpose is to evaluate, for
      example, differences in service provision and utilisation. The decomposition
      analysis helps to identify the relative influence of differences in the
      prevalence of cancer, service utilisation and productivity. 

PMID- 24462343
TI  - Length of hospital stay in Japan 1971-2008: hospital ownership and cost
      containment policies.
AB  - The average length of stay (LOS) is considered one of the most significant
      indicators of hospital management. The steep decline in the average LOS among
      Japanese hospitals since the 1980s is considered to be due to cost-containment
      policies directed at reducing LOS. Japan's hospital sector is characterised by a
      diversity of ownership types. We took advantage of this context to examine
      different hospital behaviours associated with ownership types. Analysing
      government data published from 1971 to 2008 for the effect of a series of cost
      containment policies aimed at reducing LOS revealed distinctly different paths
      behind the declines in LOS between privately owned and publicly owned hospitals.
      In the earlier years, private hospitals focused on providing long-term care to
      the elderly, while in the later years, they made a choice between providing long
      term care and providing acute care with reduced LOS and bonus payments. By
      contrast, the majority of public hospitals opted to provide acute care with
      reduced LOS in line with public targets.

PMID- 24462344
TI  - Can tissue spectrophotometry and laser Doppler flowmetry help to identify
      patients at risk for wound healing disorders after neck dissection?
AB  - OBJECTIVE: Microcirculation and oxygen supply in cervical skin were measured with
      an optical, noninvasive method in patients with or without radiotherapy before
      neck dissection. The course of wound healing was monitored after the surgical
      procedure to identify predictive factors for postoperative wound healing
      disorders. STUDY DESIGN: Tissue spectrophotometry and laser Doppler flowmetry
      were used to determine capillary oxygen saturation, hemoglobin concentration,
      blood flow, and blood velocity at 2-mm and 8-mm depths in the cervical skin of 91
      patients before neck dissection in a maxillofacial unit of a university hospital
      in Munich, Germany. Parameters were evaluated for differences between patients
      with irradiation (24) and without (67) and patients with wound healing disorders
      (25) and without (66) (univariate or multivariate statistical analyses). RESULTS:
      Velocity at 2 mm was lower in irradiated skin (P = .016). Flow at 2 mm was higher
      in patients with wound healing disorders (P = .018). CONCLUSIONS: High flow
      values could help to identify patients at risk for cervical wound healing
      disorders.

PMID- 24462345
TI  - Role of cardiac sympathetic nerves in preventing orthostatic hypotension in
      Parkinson's disease.
AB  - PURPOSE: Cardiac sympathetic denervation is associated with orthostatic
      hypotension (OH) in Parkinson's disease (PD); however, the physiological role of
      cardiac sympathetic nerves has yet to be elucidated. To clarify the role of the
      heart in orthostatic stress, we evaluated whether cardiac sympathetic nerves can
      alter cardiac activity and systolic blood pressure (BP) in association with
      elevations or depressions of total peripheral resistance during the head-up tilt
      test. METHODS: Ninety-five PD patients and 17 normal controls were enrolled.
      Using impedance cardiography, we measured total peripheral resistance, stroke
      volume, heart rate, and systolic BP during the head-up tilt test. Cardiac
      denervation was defined as a heart-to-mediastinum ratio <1.7 for cardiac (123)I
      metaiodobenzylguanidine uptake on delayed images. RESULTS: At 60 degrees  tilt,
      total peripheral resistance decreased from the initial value in 49 PD patients.
      Among these, 36 patients exhibited cardiac denervation with severe reductions in
      systolic BP but little change in stroke volume; among these patients 22 had OH.
      The remaining 13 patients without cardiac denervation exhibited significant
      increases in stroke volume and well-preserved systolic BP with no OH. On the
      other hand, 46 patients had elevations in total peripheral resistance and reduced
      stroke volume, but little change in systolic BP, regardless of the presence or
      absence of cardiac denervation. Only one of these patients experienced OH.
      CONCLUSION: Under orthostatic stress, cardiac sympathetic denervation with
      failure to increase total peripheral resistance leads to large reductions in
      systolic BP. However, patients without cardiac denervation exhibited a positive
      inotropic response against vasodilatation, which may prevent OH.

PMID- 24462346
TI  - Symptoms, location and prognosis of pulmonary embolism.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is a common disease with
      variable symptoms and high overall mortality. The clinical relevance of the
      extent of PE is still debatable, and the role of anticoagulation in patients with
      subsegmental involvement has been contested. Our objective is to describe the
      clinical details of patients with PE in our hospital and to analyze their
      prognosis based on the extent of the disease. MATERIALS AND METHODS:
      Retrospective study of 313 patients diagnosed with PE by chest computed
      tomography (CT) scan at the Hospital Complex of Pontevedra in Spain for six
      years. Predictors of mortality were determined by multivariate analysis. RESULTS:
      Women accounted for 56% of patients, and patient median age was 70 years
      (interquartile range 53-78 years). Subsegmental PE accounted for 7% of all cases;
      these patients were younger and had lower comorbidity; they reported chest pain
      more often, performed better in blood gas analysis and none of them had proximal
      deep vein thrombosis (DVT). Patients with subsegmental PE had a higher survival
      rate. Factors independently associated with mortality were cancer diagnosis and
      higher comorbidity. CONCLUSIONS: Patients with subsegmental PE clinically differ
      from those with more proximal PE. Underlying diseases have more influence on the
      prognosis than the extent of the disease.

PMID- 24462347
TI  - Chronic granulomatous disease associated with common variable immunodeficiency -
      2 clinical cases.
AB  - INTRODUCTION: Chronic granulomatous disease associated with common variable
      immunodeficiency (GD-CVID), although well documented, is rare. Granulomatous
      lesions can affect several organs and are histologically indistinguishable from
      sarcoidosis. CLINICAL CASES: Case 1: A 39-year-old male patient with CVID,
      asymptomatic although with thrombocytopenia and mediastinal-hilar adenopathies.
      GD-CVID was diagnosed by bone marrow biopsy. Progressive clinical and
      radiological improvement was obtained with corticotherapy. Case 2: A 38-year-old
      male patient with CVID, suffered from asthenia, anorexia, myalgia, lower limbs
      edemas, and dry cough. He had mediastinal and bilateral hilar adenopathies within
      which biopsy revealed non-necrotizing granulomatous infiltrate. A spontaneous
      resolution was detected after 9 months of evolution. CONCLUSION: GD-CVID is rare
      and can mimetize other pathologies, namely, sarcoidosis; it should therefore be
      publicized and discussed so that it becomes a general clinical knowledge.

PMID- 24462348
TI  - Combinations of prescription drug misuse and illicit drugs among young adults.
AB  - BACKGROUND: Prescription drug misuse remains a critical drug trend. Data indicate
      that young adults in nightlife scenes misuse prescription drugs at high rates. As
      such, continued surveillance of the patterns of prescription drug misuse among
      young adults is necessary, particularly assessments that spotlight specific areas
      of risk, such as polydrug use. METHODS: Prevalence and correlates of recent
      combinations of prescription drugs and other substances among urban young adults
      recruited at nightlife venues using time-space sampling are assessed via
      prevalence estimates and logistic regression analyses. RESULTS: Overall, 16.4% of
      the sample reported combining illicit drug use with prescription drug misuse. Of
      those who reported any prescription drug misuse, 65.9% used prescription drugs in
      combination with at least one of the illicit drugs assessed. The most common
      combination was marijuana, followed by alcohol, cocaine, ecstasy, and
      psychedelics. Being male and identifying as gay, lesbian, or bisexual predicted
      the combination of prescription drugs with ecstasy, cocaine, and psychedelics.
      CONCLUSIONS: Rates of combining alcohol and illicit drug use with prescription
      drug misuse were high, especially among men and those identified as a sexual
      minority. These rates are alarming in light of the host of negative health
      outcomes associated with combining prescription and illicit drugs.

PMID- 24462349
TI  - Fusobacterium spondylodiscitis: case report and literature review.
AB  - Fusobacteria are obligate anaerobic bacilli residing in the oral cavity, female
      genital tract, and intestine. These pathogens are typical components of head,
      neck, and abdominal abscesses due to contiguous spread from adjacent mucosal
      surfaces. They are unusual etiologies, however, of bone and joint infections,
      particularly outside the cranial region. We report an unusual case of
      hematogenous lumbar spondylodiscitis caused by Fusobacterium nucleatum of
      suspected odontogenic origin. 

PMID- 24462351
TI  - Colon-targeted celecoxib ameliorates TNBS-induced rat colitis: a potential
      pharmacologic mechanism and therapeutic advantages.
AB  - The clinical usefulness of celecoxib, a selective cyclooxygenase-2 (COX-2)
      inhibitor, for treatment of inflammatory bowel disease (IBD) is controversial in
      terms of efficacy and toxicity. To overcome these problems, colon-specific drug
      delivery was adopted, which generally confers therapeutic and toxicological
      advantages of drugs for treatment of colonic diseases. N-succinylaspart-1-yl
      celecoxib (SA1C), a colon-specific prodrug of celecoxib, was administered orally
      to rats with experimental colitis, and the anti-colitic effects and a molecular
      mechanism were investigated and compared to those of conventional celecoxib.
      SA1C, which delivered a much greater amount of celecoxib to the inflamed colon,
      alleviated the colonic injury, lowered myeloperoxidase activity in the inflamed
      colonic tissues and was much more effective than conventional celecoxib. SA1C but
      not conventional celecoxib significantly attenuated expression of NFkappaB target
      gene products in the inflamed tissues. Consistent with this, SA1C effectively
      prevented nuclear accumulation of p65 in the inflamed tissues. Moreover, while
      conventional celecoxib lowered the serum level of 6-keto-PGF1alpha, an inverse
      indicator of cardiovascular toxicity, SA1C did not change its serum level. Our
      data suggest that colonic delivery of celecoxib is a feasible strategy for
      treatment of IBD with improved therapeutic and toxicological properties.

PMID- 24462350
TI  - JM-20, a novel benzodiazepine-dihydropyridine hybrid molecule, protects
      mitochondria and prevents ischemic insult-mediated neural cell death in vitro.
AB  - The ischemic stroke cascade is composed of several pathophysiological events,
      providing multiple targets for pharmacological intervention. JM-20 (3
      ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido[2,3
      b][1,5]benzodiazepine) is a novel hybrid molecule, in which a benzodiazepine
      portion is covalently linked to a dihydropyridine ring, forming a new chemical
      entity with potential multisite neuroprotective activity. In the present study,
      JM-20 prevented PC-12 cell death induced either by glutamate, hydrogen peroxide
      or KCN-mediated chemical hypoxia. This molecule also protected cerebellar granule
      neurons from glutamate or glutamate plus pentylenetetrazole-induced damage at
      very low micromolar concentrations. In rat liver mitochondria, JM-20, at low
      micromolar concentrations, prevented the Ca2+-induced mitochondrial permeability
      transition, as assessed by mitochondrial swelling, membrane potential dissipation
      and organelle release of the pro-apoptotic protein cytochrome c. JM-20 also
      inhibited the mitochondrial hydrolytic activity of F1F0-ATP synthase and Ca2+
      influx. Therefore, JM-20 may be a multi-target neuroprotective agent, promoting
      reductions in neuronal excitotoxic injury and the protection of the mitochondria
      from Ca2+-induced impairment as well as the preservation of cellular energy
      balance.

PMID- 24462352
TI  - Histological maturation of vascular smooth muscle cells in in situ tissue
      engineered vasculature.
AB  - The goal of regenerative medicine is to achieve histological and functional
      recovery to the level of the original tissue. For this purpose, we have developed
      a biodegradable scaffold to create cell-free in-situ tissue-engineered
      vasculature (iTEV) with good long-term results. However, the regeneration process
      of vascular smooth muscle cells (VSMCs) over time has yet to be examined. To
      evaluate the regeneration ability of VSMCs, the inferior vena cava of
      experimental animals was replaced with iTEV, and tested at 1, 3, 6, 12, and 24
      months (n = 6 each) after implantation. Six animals were enrolled to compare 24
      month iTEV and native vasculature in single individual samples. There were no
      complications throughout the study. Immunohistology, protein expression analysis,
      and biochemical findings indicate that iTEV can gradually regenerate and develop
      into a mature vessel within 24 months using our biodegradable scaffold. These
      results provide a time course for the regeneration of VSMCs within the tissue
      engineered vascular autograft constructed using a biodegradable scaffold.

PMID- 24462354
TI  - In vitro chondrogenesis and in vivo repair of osteochondral defect with human
      induced pluripotent stem cells.
AB  - The purpose of this study was to investigate the chondrogenic features of human
      induced pluripotent stem cells (hiPSCs) and examine the differences in the
      chondrogenesis between hiPSCs and human bone marrow-derived MSCs (hBMMSCs).
      Embryoid bodies (EBs) were formed from undifferentiated hiPSCs. After EBs were
      dissociated into single cells, chondrogenic culture was performed in pellets and
      alginate hydrogel. Chondro-induced hiPSCs were implanted in osteochondral defects
      created on the patellar groove of immunosuppressed rats and evaluated after 12
      weeks. The ESC markers NANOG, SSEA4 and OCT3/4 disappeared while the mesodermal
      marker BMP-4 appeared in chondro-induced hiPSCs. After 21 days of culture,
      greater glycosaminoglycan contents and better chondrocytic features including
      lacuna and abundant matrix formation were observed from chondro-induced hiPSCs
      compared to chondro-induced hBMMSCs. The expression of chondrogenic markers
      including SOX-9, type II collagen, and aggrecan in chondro-induced hiPSCs was
      comparable to or greater than chondro-induced hBMMSCs. A remarkably low level of
      hypertrophic and osteogenic markers including type X collagen, type I collagen
      and Runx-2 was noted in chondro-induced hiPSCs compared to chondro-induced
      hBMMSCs. hiPSCs had significantly greater methylation of several CpG sites in
      COL10A1 promoter than hBMMSCs in either undifferentiated or chondro-induced
      state, suggesting an epigenetic cause of the difference in hypertrophy. The
      defects implanted with chondro-induced hiPSCs showed a significantly better
      quality of cartilage repair than the control defects, and the majority of cells
      in the regenerated cartilage consisted of implanted hiPSCs. 

PMID- 24462353
TI  - The bioactivity of agarose-PEGDA interpenetrating network hydrogels with
      covalently immobilized RGD peptides and physically entrapped aggrecan.
AB  - Our previous reports of interpenetrating networks (IPNs) have demonstrated
      drastic improvements in mechanical performance relative to individual constituent
      networks while maintaining viability of encapsulated cells. The current study
      investigated whether covalent linkage of RGD to the poly(ethylene glycol)
      diacrylate (PEGDA) network could improve upon cell viability and performance of
      agarose-PEGDA IPNs compared to unmodified IPNs (control) and to IPNs with
      different concentrations of physically entrapped aggrecan, providing a point of
      comparison to previous work. The inclusion of RGD or aggrecan generally did not
      adversely affect mechanical performance, and significantly improved chondrocyte
      viability and performance. Although both 4 and 100 MUg/mL of aggrecan improved
      cell viability, only 100 MUg/mL aggrecan was clearly beneficial to improving
      biosynthesis, whereas 100 MUg/mL of RGD was beneficial to both chondrocyte
      viability and biosynthesis. Interestingly, clustering of cells within the IPNs
      with RGD and the higher aggrecan concentration were observed, likely indicating
      cell migration and/or preferred regional proliferation. This clustering resulted
      in a clearly visible enhancement of matrix production compared to the other IPNs.
      With this cell migration, we also observed significant cell proliferation and
      matrix synthesis beyond the periphery of the IPN, which could have important
      implications in facilitating integration with surrounding cartilage in vivo. With
      RGD and aggrecan (at its higher concentration) providing substantial and
      comparable improvements in cell performance, RGD would be the recommended
      bioactive signal for this particular IPN formulation and cell source given the
      significant cost savings and potentially more straightforward regulatory pathway
      in commercialization.

PMID- 24462355
TI  - A role for c-Kit in the maintenance of undifferentiated human mesenchymal stromal
      cells.
AB  - The multipotency of human mesenchymal stromal cells (hMSCs) and the feasibility
      of deriving these cells from periodontal ligament hold promise for stem cell
      based tissue engineering. However, the regulation of adult hMSCs activity is not
      well understood. The present study investigated the c-Kit surface receptor and
      downstream gene expression in hMSCs. The c-Kit-positive population showed
      increased colony-forming ability rather than differentiation potential. The
      knockdown of c-Kit and/or stem cell factor (SCF) genes enhanced alkaline
      phosphatase activity and also upregulated osteoblast- and adipocyte-specific
      genes, including osteocalcin, runt-related transcription factor 2, osteopontin,
      peroxisome proliferator-activated receptor-gamma, and lipoprotein lipase.
      Stimulation with growth factors, including fibroblast growth factor-2,
      transforming growth factor-beta1, and enamel matrix derivative significantly
      suppressed the mRNA expression of c-Kit. These results support an emerging
      understanding of the roles of the c-Kit/SCF signal in maintaining the
      undifferentiated stage of hMSCs by inhibiting the expression of lineage-specific
      genes in hMSCs and regulating the effect of growth factors on the proliferation
      and differentiation of hMSCs. The modulation of c-Kit/SCF signaling might
      contribute to future regenerative approaches in controlling both the stemness and
      differentiation properties of hMSCs. 

PMID- 24462357
TI  - The role of valvular endothelial cell paracrine signaling and matrix elasticity
      on valvular interstitial cell activation.
AB  - The effects of valvular endothelial cell (VlvEC) paracrine signaling on VIC
      phenotype and nodule formation were tested using a co-culture platform with
      physiologically relevant matrix elasticities and diffusion distance. 100 MUm thin
      poly(ethylene glycol) (PEG) hydrogels of 3-27 kPa Young's moduli were fabricated
      in transwell inserts. VICs were cultured on the gels, as VIC phenotype is known
      to change significantly within this range, while VlvECs lined the underside of
      the membrane. Co-culture with VlvECs significantly reduced VIC activation to the
      myofibroblast phenotype on all gels with the largest percent decrease on the 3
      kPa gels (~70%), while stiffer gels resulted in approximately 20-30% decrease.
      Additionally, VlvECs significantly reduced alphaSMA protein expression (~2 fold
      lower) on both 3 and 27 kPa gels, as well as the number (~2 fold lower) of
      nodules formed on the 27 kPa gels. Effects of VlvECs were prevented when nitric
      oxide (NO) release was inhibited with l-NAME, suggesting that VlvEC produced NO
      inhibits VIC activation. Withdrawal of l-NAME after 3, 5, and 7 days with
      restoration of VlvEC NO production for 2 additional days led to a partial
      reversal of VIC activation (~25% decrease). A potential mechanism by which VlvEC
      produced NO reduced VIC activation was studied by inhibiting initial and mid
      stage cGMP pathway molecules. Inhibition of soluble guanylyl cyclase (sGC) with
      ODQ or protein kinase G (PKG) with RBrcGMP or stimulation of Rho kinase (ROCK)
      with LPA, abolished VlvEC effects on VIC activation. This work contributes
      substantially to the understanding of the valve endothelium's role in preventing
      VIC functions associated with aortic valve stenosis initiation and progression.

PMID- 24462356
TI  - Integrin-directed modulation of macrophage responses to biomaterials.
AB  - Macrophages are the primary mediator of chronic inflammatory responses to
      implanted biomaterials, in cases when the material is either in particulate or
      bulk form. Chronic inflammation limits the performance and functional life of
      numerous implanted medical devices, and modulating macrophage interactions with
      biomaterials to mitigate this response would be beneficial. The integrin family
      of cell surface receptors mediates cell adhesion through binding to adhesive
      proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the
      roles of integrin Mac-1 (alphaMbeta2) and RGD-binding integrins were investigated
      using model systems for both particulate and bulk biomaterials. Specifically, the
      macrophage functions of phagocytosis and inflammatory cytokine secretion in
      response to a model particulate material, polystyrene microparticles were
      investigated. Opsonizing proteins modulated microparticle uptake, and integrin
      Mac-1 and RGD-binding integrins were found to control microparticle uptake in an
      opsonin-dependent manner. The presence of adsorbed endotoxin did not affect
      microparticle uptake levels, but was required for the production of inflammatory
      cytokines in response to microparticles. Furthermore, it was demonstrated that
      integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body
      response to a bulk biomaterial, subcutaneously implanted polyethylene
      terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was
      absent (~30% thinner) or when RGD-binding integrins were blocked by controlled
      release of a blocking peptide (~45% thinner). These findings indicate integrin
      Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets
      to mitigate macrophage inflammatory responses to both particulate and bulk
      biomaterials.

PMID- 24462358
TI  - Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for
      targeted tumor MR imaging.
AB  - We report a polyethyleneimine (PEI)-mediated approach to synthesizing hyaluronic
      acid (HA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo
      targeted tumor magnetic resonance (MR) imaging applications. In this work, Fe3O4
      NPs stabilized by PEI were first synthesized via a one-pot hydrothermal method.
      The formed PEI-stabilized Fe3O4 NPs were then modified with fluorescein
      isothiocyanate (FI) and HA with two different molecular weights to obtain two
      different Fe3O4 NPs (Fe3O4-PEI-FI-HA6K and Fe3O4-PEI-FI-HA31K NPs) with a size of
      15-16 nm. The formed HA-modified multifunctional Fe3O4 NPs were characterized via
      different techniques. We show that the multifunctional Fe3O4 NPs are water
      dispersible and colloidal stable in different aqueous media. In vitro cell
      viability and hemolysis studies reveal that the particles are quite
      cytocompatible and hemocompatible in the given concentration range. Furthermore,
      confocal microscopy and flow cytometry data demonstrate that HA-targeted Fe3O4
      NPs are able to be uptaken specifically by cancer cells overexpressing CD44
      receptors, and be used as efficient probes for targeted MR imaging of cancer
      cells in vitro and xenografted tumor models in vivo. With the tunable amine-based
      conjugation chemistry, the PEI-stabilized Fe3O4 NPs may be functionalized with
      other biological ligands or drugs for diagnosis and therapy of different
      biological systems.

PMID- 24462359
TI  - Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for
      release of chemotherapeutics in multidrug resistant cancer cells.
AB  - Multidrug resistance (MDR) is a major impediment to the success of cancer
      chemotherapy. A polymer-lipid supported mesoporous silica nanoparticle (PLS-MSNs)
      is described here to facilitate intracellular delivery of anticancer drug and
      enhance the antitumor efficacy against MDR breast cancer cells. By coating MSNs
      with a synthetic dual-functional polymer-lipid material P123-DOPE, the supported
      membrane acted as an intact barrier against the escape of encapsulated drugs
      before reaching the target cells, leading to depolymerization and triggered storm
      release of loaded irinotecan (CPT-11) in acidic endosomal pH of tumor cells. In
      addition, P123-DOPE can inhibit breast cancer resistance protein (BCPR) mediated
      CPT-11 efflux in drug resistant MCF-7/BCRP breast cancer cells, thus acting as a
      "door blocker". Compared to free CPT-11, PLS-MSNs resulted in a maximum increase
      in the intracellular CPT-11 concentration (12.9-fold), had 7.1-fold higher
      cytotoxicity and processed a stronger cell cycle arrest in MCF-7/BCRP cells.
      Moreover, CPT-11 loaded PLS-MSNs showed high therapeutic performance and low
      toxicity in BALB/c nude mice bearing drug resistant breast tumors, with an
      inhibition rate of 81.2% compared to free CPT-11 treatment group. The reported
      PLS-MSNs provide promising applicability in future preclinical and clinical MDR
      cancer treatment. 

PMID- 24462360
TI  - Stemness and transdifferentiation of adipose-derived stem cells using L-ascorbic
      acid 2-phosphate-induced cell sheet formation.
AB  - Cell sheet technology has emerged as an important tissue engineering approach.
      Adipose-derived stem cells (ASCs) have valuable applications in regenerative
      medicine, but their stemness and differentiation capabilities in the cell sheet
      format have not been well investigated. In this study, we found that l-ascorbate
      2-phosphate (A2-P), a stable form of ascorbic acid, significantly enhanced ASC
      proliferation and induced ASC sheet fabrication in 7 days with abundant
      extracellular matrix deposition. Importantly, A2-P treatment significantly
      enhanced expression of pluripotent markers Sox-2, Oct-4 and Nanog, but treating
      ASCs with antioxidants other than A2-P revealed no stemness enhancement.
      Moreover, ASC treatment with A2-P and a collagen synthesis inhibitor, L-2
      azetidine carboxylic acid or cis-4-hydroxy-d-proline, significantly inhibited the
      A2-P-enhanced expression of stemness markers. These findings demonstrated that A2
      P enhances stemness of ASCs through collagen synthesis and cell sheet formation.
      We also showed that A2-P-stimulated collagen synthesis in ASCs may be mediated
      through ERK1/2 pathway. By culturing the ASC sheets in proper induction media,
      ASC transdifferentiation capabilities into neuron and hepatocyte-like cells were
      significantly enhanced after cell sheet formation, while adipogenic and
      osteogenic differentiation capacities were still maintained. Using a murine model
      of healing-impaired cutaneous wound, faster wound healing was noted in the group
      that received ASC sheet treatment, and we observed significantly more engrafted
      ASCs with evidence of differentiation toward endothelial and epidermal lineages
      in the cutaneous wound tissue. Therefore, A2-P-mediated ASC sheet formation
      enhanced ASC stemness and transdifferentiation capabilities, thereby representing
      a promising approach for applications in regenerative medicine. 

PMID- 24462361
TI  - Cryo-chemical decellularization of the whole liver for mesenchymal stem cells
      based functional hepatic tissue engineering.
AB  - Liver transplantation is the ultimate treatment for severe hepatic failure to
      date. However, the limited supply of donor organs has severely hampered this
      treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to
      replenish the hepatic cell population have been shown; nevertheless, there still
      is a lack of an optimal three-dimensional scaffold for generation of well
      transplantable hepatic tissues. In this study, we utilized a cryo-chemical
      decellularization method which combines physical and chemical approach to
      generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS
      provides a biomimetic three-dimensional environment to support hepatic
      differentiation of MSCs, evidenced by expression of hepatic-associated genes and
      marker protein, glycogen storage, albumin secretion, and urea production. It is
      also found that hepatic differentiation of MSCs within the ALS is much more
      efficient than two-dimensional culture in vitro. Importantly, the hepatic-like
      tissues (HLT) generated by repopulating ALS with MSCs are able to act as
      functional grafts and rescue lethal hepatic failure after transplantation in
      vivo. In summary, the cryo-chemical method used in this study is suitable for
      decellularization of liver and create acellular scaffolds that can support
      hepatic differentiation of MSCs and be used to fabricate functional tissue
      engineered liver constructs.

PMID- 24462363
TI  - Multi-stage continuous high cell density culture systems: a review.
AB  - A multi-stage continuous high cell density culture (MSC-HCDC) system makes it
      possible to achieve high productivity together with high product titer of many
      bioproducts. For long-term continuous operation of MSC-HCDC systems, the cell
      retention time and hydraulic retention time must be decoupled and strains
      (bacteria, yeast, plant, and animal cells) must be stable. MSC-HCDC systems are
      suitable for low-value high-volume extracellular products such as fuel ethanol,
      lactic acid or volatile fatty acids, and high-value products such as monoclonal
      antibodies as well as intracellular products such as polyhydroxybutyric acid
      (PHB), microbial lipids or a number of therapeutics. Better understanding of the
      fermentation kinetics of a specific product and reliable high-density culture
      methods for the product-generating microorganisms will facilitate timely
      industrialization of MSC-HCDC systems for products that are currently obtained in
      fed-batch bioreactors.

PMID- 24462362
TI  - Mediation of a non-proteolytic activation of complement component C3 by
      phospholipid vesicles.
AB  - Liposomes are becoming increasingly important as drug delivery systems, to target
      a drug to specific cells and tissues and thereby protecting the recipient from
      toxic effects of the contained drug. Liposome preparations have been described to
      activate complement. In this study, we have investigated complement activation
      triggered by neutral dimyristoyl-phosphocholine (DMPC) liposomes in human plasma
      and whole-blood systems. Incubation in plasma led to the generation of complement
      activation products (C3a and sC5b-9). Unexpectedly, investigations of surface
      bound C3 revealed contact activated, conformationally changed C3 molecules on the
      liposomes. These changes were characterized by Western blotting with C3
      monoclonal antibodies, and by incubating liposomes with purified native C3 and
      factors I and H. Quartz crystal microbalance analysis confirmed binding of C3 to
      planar DMPC surfaces. In addition, we demonstrated that DMPC liposomes bound to
      or were phagocytized by granulocytes in a complement-dependent manner, as
      evidenced by the use of complement inhibitors. In summary, we have shown that C3
      is activated both by convertase-dependent cleavage, preferentially in the fluid
      phase, by mechanisms which are not well elucidated, and also by contact
      activation into C3(H2O) on the DMPC surface. In particular, this contact
      activation has implications for the therapeutic regulation of complement
      activation during liposome treatment. 

PMID- 24462364
TI  - Feeding of banana flower and pseudostem to diabetic rats results in modulation of
      renal GLUTs, TGFbeta, PKC and extracellular matrix components.
AB  - BACKGROUND AND AIMS: Sustained hyperglycemia as a result of diabetes mellitus
      results in over-expression of glucose transporters (GLUTs/SGLTs), protein kinase
      C-alpha (PKC-alpha) and transforming growth factor-beta (TGF-beta) in kidney
      which increases synthesis and accumulation of extracellular matrix (ECM)
      components leading to diabetic nephropathy. Previous results from our laboratory
      showed that banana flower (BF) and pseudostem (BS) ameliorated diabetic
      complications and reduced formation of advanced glycation end-products (AGEs). In
      this study, attempts were made to delineate the changes observed in GLUTs and ECM
      components in kidney by feeding BF and BS at the molecular level. METHODS AND
      RESULTS: Diabetes was induced in male Wistar rats by injecting streptozotocin.
      Rats were fed with standard AIN-76 diet or diet supplemented with 5% BF or BS.
      Rats fed with diet supplemented with aminoguanidine (0.05%) were used as a
      positive control. Effect of BF and BS on expression of GLUTs/SGLTs, PKC and TGF
      beta in kidney was evaluated by RT-PCR and accumulation of ECM components in
      kidney was quantitated by ELISA and immunohistochemistry. BF and BS modulated the
      over-expression of GLUT 1, 2, 5, SGLT 1, 2 and factors such as PKC-alpha and TGF
      beta to various extents. This impinged on the synthesis of ECM components like
      laminin, fibronectin and type-IV collagen. CONCLUSION: The results suggest that
      BF and BS reduce the diabetic nephropathy complications which are accompanied by
      changes at the molecular level.

PMID- 24462365
TI  - Pentraxin 3 (PTX3) plasma levels and carotid intima media thickness progression
      in the general population.
AB  - BACKGROUND AND AIM: Pentraxin 3 (PTX3) is an essential component of the humoral
      arm of innate immunity and, like C-reactive protein, is independently associated
      with the risk of developing vascular events. Aim of this study was to
      investigate, in two large population-based surveys, the Bruneck Study and the
      PLIC Study, whether PTX3 plasma levels predict the progression of common carotid
      artery intima-media thickness (CCA-IMT), a surrogate marker of atherosclerosis,
      in the general population during 5 or 6 years of follow-up. RESULTS: In the
      Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT
      either in the carotid artery or in the femoral artery. This finding was confirmed
      in the PLIC Study where subjects within the highest tertile of PTX3 did not show
      an increased progression of CCA-IMT. PTX3 plasma levels were also not associated
      with the fastest maximum IMT progression. In summary, in more than 2400 subjects
      from the general population, PTX3 plasma level is neither an independent
      predictor of progression of subclinical atherosclerosis in different arterial
      territories, including carotid and femoral arteries nor of incident
      cardiovascular events. CONCLUSION: These findings support the relevance of
      investigating the predictive value of PTX3 plasma levels only in specific
      settings, like overt CVD, heart failure or acute myocardial infarction.

PMID- 24462366
TI  - Dietary patterns and 1-h post-load glucose in essential hypertension.
AB  - BACKGROUND AND AIMS: Normoglucosetolerants (NGT) are considered at low risk, even
      if a 1-h post-load glucose (PLG) value >= 155 mg dl(-1) identifies NGTs at high
      risk of type-2 diabetes (T2D) and sub-clinical organ damage. Specific dietary
      factors may affect insulin sensitivity and the risk of T2D. However, it is
      unknown whether dietary components affect 1-h PLG in hypertensive NGT. Therefore,
      we investigate the effect of dietary patterns on 1-h PLG. METHODS AND RESULTS: We
      selected 188 subjects (94 NGTs < 155 mg dl(-1) and 94 NGTs >= 155 mg dl(-1) PLG),
      well matched for age, gender and body mass index (BMI). Insulin sensitivity was
      evaluated using the Matsuda index. Dietary intake was quantified by a
      semiquantitative food frequency questionnaire (FEQ) validated in the European
      Investigation into Cancer and Nutrition (EPIC) study. The NGT >= 155 group had
      significantly reduced insulin sensitivity (40.3 +/- 19.8 vs. 73.3 +/- 28.8; P <
      0.0001). With the exclusion of total calories, lipids, alcohol and fiber
      consumption we observed a significant difference, between groups, in starch
      (214.1 +/- 52.4 vs. 268.8 +/- 71.8 g; P < 0.0001), saturated (27.4 +/- 8.7 vs.
      24.1 +/- 8.5 g; P = 0.009), monounsaturated (45.5 +/- 8.9 vs. 48.8 +/- 10.7 g; P
      = 0.023) and polyunsaturated fatty acids (FAs) (14.5 +/- 4.0 vs. 16.8 +/- 4.7 g;
      P < 0.0001), fructose (14.5 +/- 5.3 vs. 11.2 +/- 4.8 g; P < 0.0001), and
      oligosaccharides (103.2 +/- 26.6 vs. 89.9 +/- 29.2 g; P = 0.001) consumption. In
      the whole population, starch was the major predictor of 1-h PLG, explaining 23.2%
      of variation (P < 0.0001). In the NGT < 155 group, fructose was the strongest
      predictor, accounting for 15.4% of the variation; BMI, gender and polyunsaturated
      FAs added another 6.6%, 3.6% and 3.2%, respectively. In the NGT >= 155 group,
      saturated and polyunsaturated FAs were retained as the major predictors of 1-h
      PLG, explaining 18.2% and 11.4% of the variation. CONCLUSIONS: The present data
      demonstrate that dietary patterns affect 1-h PLG, remarking the importance of
      both quantitative and qualitative composition of a diet.

PMID- 24462367
TI  - Oxidised LDL levels decreases after the consumption of ready-to-eat meals
      supplemented with cocoa extract within a hypocaloric diet.
AB  - BACKGROUND AND AIMS: Cocoa flavanols are recognised by their favourable
      antioxidant and vascular effects. This study investigates the influence on health
      of the daily consumption of ready-to-eat meals supplemented with cocoa extract
      within a hypocaloric diet, on middle-aged overweight/obese subjects. METHODS AND
      RESULTS: Fifty healthy male and female middle-aged volunteers [57.26 +/- 5.24
      years and body mass index (BMI) 30.59 +/- 2.33 kg/m(2)] were recruited to
      participate in a 4 week randomised, parallel and double-blind study. After
      following 3 days on a low-polyphenol diet, 25 volunteers received meals
      supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other
      25 participants received control meals, within a 15% energy restriction diet. On
      the 4th week of intervention individuals in both dietary groups improved (p <
      0.05) anthropometric, body composition, blood pressure and blood biochemical
      measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction (p =
      0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only
      in the cocoa supplemented group (p = 0.007). Intercellular Adhesion Molecule-1
      (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion
      Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of
      intervention. Interestingly, cocoa intake showed a different effect by gender,
      presenting more beneficial effects in men. CONCLUSIONS: The consumption of cocoa
      extract as part of ready-to-eat meals and within a hypocaloric diet improved
      oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males.
      REGISTRATION NUMBER: Registered at www.clinicaltrials.gov (NCT01596309).

PMID- 24462368
TI  - Clinical and economical impact of 2010 AASLD guidelines for the diagnosis of
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Although contrast-enhanced computed tomography (CT), dynamic
      magnetic resonance (MRI) and fine needle biopsy (FNB) are the standard of care to
      diagnose hepatocellular carcinoma (HCC), the clinical and economic benefits of
      the updated AASLD diagnostic algorithm, including the drop of contrast enhanced
      ultrasound (CEUS), have not been previously evaluated. METHODS: 119 de novo liver
      nodules detected during ultrasound (US) surveillance in 98 cirrhotics, 7 <1cm, 67
      1-2cm, 45 >2cm in size, were sequentially examined by CEUS and CT, using MRI as a
      rescue approach in patients lacking a typical vascular pattern for HCC by one or
      both contrast techniques in the 1-2cm nodules and by CT in the >2cm nodules. A
      FNB was performed when required to meet both 2005 and 2010 AASLD criteria.
      RESULTS: Eighty-four (70%) nodules were HCC: the radiological diagnosis was done
      in 38 (88%) of those 1-2cm and in 38 (95%) for those >2cm HCCs according to 2010
      AASLD criteria. CT or MRI detected 13 HCC nodules that were missed by unenhanced
      US. Despite an absolute specificity, CEUS failed to identify any HCC
      uncharacterized by CT or MRI. By updated AASLD criteria, 6 (17%) FNB procedures
      were spared in patients with 1-2cm nodules (p=0.025), as compared to 2005
      criteria. The 2010 vs. 2005 AASLD per patient cost was similar in 1-2cm nodules,
      432 ? vs. 451 ? (p=0.46), but lower in >2cm nodules, 248 ? vs. 321 ? (p<0.001).
      CONCLUSIONS: A sequential study with either CT or MRI enhances the radiological
      diagnosis of HCC and reduces costs and liver biopsy need.

PMID- 24462369
TI  - A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese
      individuals with Leigh syndrome.
AB  - Leigh syndrome (LS) is a severe neurodegenerative disorder with characteristic
      bilateral lesions, typically in the brainstem and basal ganglia. It usually
      presents in infancy and is genetically heterogeneous, but most individuals with
      mitochondrial complex IV (or cytochrome c oxidase) deficiency have mutations in
      the biogenesis factor SURF1. We studied eight complex IV-deficient LS individuals
      from six families of Lebanese origin. They differed from individuals with SURF1
      mutations in having seizures as a prominent feature. Complementation analysis
      suggested they had mutation(s) in the same gene but targeted massively parallel
      sequencing (MPS) of 1,034 genes encoding known mitochondrial proteins failed to
      identify a likely candidate. Linkage and haplotype analyses mapped the location
      of the gene to chromosome 19 and targeted MPS of the linkage region identified a
      homozygous c.3G>C (p.Met1?) mutation in C19orf79. Abolishing the initiation codon
      could potentially still allow initiation at a downstream methionine residue but
      we showed that this would not result in a functional protein. We confirmed that
      mutation of this gene was causative by lentiviral-mediated phenotypic correction.
      C19orf79 was recently renamed PET100 and predicted to encode a complex IV
      biogenesis factor. We showed that it is located in the mitochondrial inner
      membrane and forms a ~300 kDa subcomplex with complex IV subunits. Previous
      proteomic analyses of mitochondria had overlooked PET100 because its small size
      was below the cutoff for annotating bona fide proteins. The mutation was
      estimated to have arisen at least 520 years ago, explaining how the families
      could have different religions and different geographic origins within Lebanon.

PMID- 24462370
TI  - Causal effects of body mass index on cardiometabolic traits and events: a
      Mendelian randomization analysis.
AB  - Elevated body mass index (BMI) associates with cardiometabolic traits on
      observational analysis, yet the underlying causal relationships remain unclear.
      We conducted Mendelian randomization analyses by using a genetic score (GS)
      comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate
      the causal role of BMI in cardiometabolic traits and events. We used eight
      population-based cohorts, including 34,538 European-descent individuals (4,407
      type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke
      cases). A 1 kg/m(2) genetically elevated BMI increased fasting glucose (0.18
      mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI
      = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure
      (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol
      (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol
      (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal
      estimates were directionally concordant, except for LDL-C. A 1 kg/m(2)
      genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95%
      CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or
      stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published
      studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of
      1.04 (95% CI = 0.97-1.12) per 1 kg/m(2) increase in BMI. In conclusion, we
      identified causal effects of BMI on several cardiometabolic traits; however,
      whether BMI causally impacts CHD risk requires further evidence.

PMID- 24462371
TI  - Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic
      optic fissure closure defects.
AB  - Exome sequence analysis of affected individuals from two families with autosomal
      dominant inheritance of coloboma identified two different cosegregating
      heterozygous nonsense mutations (c.370C>T [p.Arg124*] and c. 1066G>T [p.Glu356*])
      in YAP1. The phenotypes of the affected families differed in that one included no
      extraocular features and the other manifested with highly variable multisystem
      involvement, including hearing loss, intellectual disability, hematuria, and
      orofacial clefting. A combined LOD score of 4.2 was obtained for the association
      between YAP1 loss-of-function mutations and the phenotype in these families. YAP1
      encodes an effector of the HIPPO-pathway-induced growth response, and whole-mount
      in situ hybridization in mouse embryos has shown that Yap1 is strongly expressed
      in the eye, brain, and fusing facial processes. RT-PCR showed that an alternative
      transcription start site (TSS) in intron 1 of YAP1 and Yap1 is widely used in
      human and mouse development, respectively. Transcripts from the alternative TSS
      are predicted to initiate at codon Met179 relative to the canonical transcript
      (RefSeq NM_001130145). In these alternative transcripts, the c.370C>T mutation in
      family 1305 is within the 5' UTR and cannot result in nonsense-mediated decay
      (NMD). The c. 1066G>T mutation in family 132 should result in NMD in transcripts
      from either TSS. Amelioration of the phenotype by the alternative transcripts
      provides a plausible explanation for the phenotypic differences between the
      families.

PMID- 24462372
TI  - NR2F1 mutations cause optic atrophy with intellectual disability.
AB  - Optic nerve atrophy and hypoplasia can be primary disorders or can result from
      trans-synaptic degeneration arising from cerebral visual impairment (CVI). Here
      we report six individuals with CVI and/or optic nerve abnormalities, born after
      an uneventful pregnancy and delivery, who have either de novo heterozygous
      missense mutations in NR2F1, also known as COUP-TFI, or deletions encompassing
      NR2F1. All affected individuals show mild to moderate intellectual impairment.
      NR2F1 encodes a nuclear receptor protein that regulates transcription. A reporter
      assay showed that missense mutations in the zinc-finger DNA-binding domain and
      the putative ligand-binding domain decrease NR2F1 transcriptional activity. These
      findings indicate that NR2F1 plays an important role in the neurodevelopment of
      the visual system and that its disruption can lead to optic atrophy with
      intellectual disability.

PMID- 24462373
TI  - Novel therapy for nasopharyngeal carcinoma--where are we.
AB  - Nasopharyngeal carcinoma (NPC) is endemic in Southern China, and the South-East
      Asia including Hong Kong. We still see patients recur after primary treatment
      with radiotherapy or chemo-irradiation. Management of nasopharyngeal carcinoma
      remains one of the biggest clinical challenges. There have been breakthroughs in
      early detection, diagnosis, multi-modality treatment and also disease monitoring
      for NPC. Systemic treatment has been crucial to the management of locally
      advanced or metastatic NPC. With the advent of molecular targeted therapy and
      personalized medicine, novel therapies based on molecular targets of NPC have
      become the focus of research and development over the last decade. Furthermore,
      as NPC is tightly associated with the Epstein-Barr virus (EBV) infection, the
      role of tumor-associated viral antigens in NPC renders it an appealing candidate
      for cellular immunotherapy. This is a review of recent evolving concerted efforts
      and the success from our translational research with focus of the recent systemic
      novel targeted therapies including the potential role of immunotherapy which may
      offer further clinical benefit to our patients living with NPC. The scientific
      basis and latest published results of the relevant clinical trials are
      highlighted, demonstrating the ongoing battle against NPC is indeed one of the
      most fascinating successes in head and neck oncology.

PMID- 24462374
TI  - Enzalutamide after failure of docetaxel and abiraterone in metastatic castrate
      resistant prostate cancer.

PMID- 24462375
TI  - Regulation of exosome release from mammary epithelial and breast cancer cells - a
      new regulatory pathway.
AB  - PURPOSE: Exosomes are small 50-100nm sized extracellular vesicles released from
      normal and tumour cells and are a source of a new intercellular communication
      pathway. Tumour exosomes promote tumour growth and progression. What regulates
      the release and homoeostatic levels of exosomes, in cancer, in body fluids
      remains undefined. METHODS: We utilised a human mammary epithelial cell line
      (HMEC B42) and a breast cancer cell line derived from it (B42 clone 16) to
      investigate exosome production and regulation. Exosome numbers were quantified
      using a Nanosight LM10 and measured in culture supernatants in the absence and
      presence of exosomes in the medium. Concentrated suspensions of exosomes from the
      normal mammary epithelial cells, the breast cancer cells and bladder cancer cells
      were used. The interaction of exosomes with tumour cells was also investigated
      using fluorescently labelled exosomes. RESULTS: Exosome release from normal human
      mammary epithelial cells and breast cancer cells is regulated by the presence of
      exosomes, derived from their own cells, in the extracellular environment of the
      cells. Exosomes from normal mammary epithelial cells also inhibit exosome
      secretion by breast cancer cells, which occurs in a tissue specific manner.
      Labelled exosomes from mammary epithelial cells are internalised into the tumour
      cells implicating a dynamic equilibrium and suggesting a mechanism for feedback
      control. CONCLUSIONS: These data suggest a previously unknown novel feedback
      regulatory mechanism for controlling exosome release, which may highlight a new
      therapeutic approach to controlling the deleterious effects of tumour exosomes.
      This regulatory mechanism is likely to be generic to other tumours.

PMID- 24462376
TI  - Frondoside A enhances the antiproliferative effects of gemcitabine in pancreatic
      cancer.
AB  - Pancreatic cancer has a very poor prognosis. While gemcitabine is the mainstay of
      therapy and improves quality of life, it has little impact on survival. More
      effective treatments are desperately needed for this disease. Frondoside A is a
      triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria
      frondosa. Frondoside A potently inhibits pancreatic cancer cell growth and
      induces apoptosis in vitro and in vivo. The aim of the present study was to
      investigate whether frondoside A could enhance the anti-cancer effects of
      gemcitabine. Effects of frondoside A and gemcitabine alone and in combination on
      proliferation were investigated in two human pancreatic cancer cell lines, AsPC-1
      and S2013. To investigate possible synergistic effects, combinations of low
      concentrations of the two drugs were used for a 72 h treatment period in vitro.
      Growth inhibition was significantly greater with the drug combinations than their
      additive effects. Combinations of frondoside A and gemcitabine were tested in
      vivo using the athymic mouse model. Xenografts of AsPC-1 and S2013 cells were
      allowed to form tumours prior to treatment with the drugs alone or in combination
      for 30 days. Tumours grew rapidly in placebo-treated animals. Tumour growth was
      significantly reduced in all treatment groups. At the lowest dose tested,
      gemcitabine (4 mg/kg/dose), combined with frondoside A (100 MUg/kg/day) was
      significantly more effective than with either drug alone. To conclude: The
      present data suggest that combinations of frondoside A and gemcitabine may
      provide clinical benefit for patients with pancreatic cancer.

PMID- 24462377
TI  - Resistance to human epidermal growth factor receptor type 2-targeted therapies.
AB  - The overexpression of the human epidermal growth factor receptor type 2 (HER-2)
      is an independent prognostic factor of poor outcome in patients with breast
      cancer. Two compounds have been registered for HER-2-positive tumour treatment:
      trastuzumab, a humanised antibody directed against the HER-2 extracellular
      domain, and lapatinib, a small molecule acting as a dual EGF-R and HER-2 tyrosine
      kinase inhibitor. Although both drugs improve progression-free survival, many
      patients' tumours will exhibit primary resistance, or develop secondary
      resistance, to anti-HER-2 therapies. The recent significant improvement of
      survival gained with pertuzumab (an antibody disrupting dimerisation of the
      receptor) or trastuzumab emtansine (T-DM1, a cytotoxic drug vectored by
      trastuzumab binding) opened the way for new registrations. This review describes
      the molecular mechanisms by which tumour cells may adapt to and evade HER-2
      inhibition by HER-2-targeted therapies and discusses strategies to prevent and
      overcome resistance to trastuzumab and lapatinib. These strategies may include
      the establishment of predictive markers, exploration of combination therapies and
      modulation of nodal targets. 

PMID- 24462378
TI  - [Conidiobolus coronatus infections revealed by a facial tumor].
AB  - INTRODUCTION: Conidiobolomycoses (Conidiobolus coronatus fungal infections) are
      rare and potentially severe infections prevalent in the tropics. The disease
      starts in the facial sinus and evolves as a subcutaneous tumor on the mid face
      OBSERVATION: A 19-year-old female patient from Burkina Faso presented with an
      acquired nasal deformation having evolved for a few months, associated to
      bilateral nasal obstruction. The patient had no medical or surgical history. The
      pathological analysis of the surgical exeresis allowed diagnosing a C. coronatus
      infection. DISCUSSION: The C. coronatus lives in decaying vegetation in hot and
      humid climates. It is a potential human pathogen that infects immunocompetent
      patients presenting with micro-wounds of the sinus and nasal mucosa. Hundred
      cases have been reported. The management is specific. The diagnosis should be
      discussed in case of distorting tumors of the midface.

PMID- 24462379
TI  - The influence of anisotropy on brain injury prediction.
AB  - Traumatic Brain Injury (TBI) occurs when a mechanical insult produces damage to
      the brain and disrupts its normal function. Numerical head models are often used
      as tools to analyze TBIs and to measure injury based on mechanical parameters.
      However, the reliability of such models depends on the incorporation of an
      appropriate level of structural detail and accurate representation of the
      material behavior. Since recent studies have shown that several brain regions are
      characterized by a marked anisotropy, constitutive equations should account for
      the orientation-dependence within the brain. Nevertheless, in most of the current
      models brain tissue is considered as completely isotropic. To study the influence
      of the anisotropy on the mechanical response of the brain, a head model that
      incorporates the orientation of neural fibers is used and compared with a fully
      isotropic model. A simulation of a concussive impact based on a sport accident
      illustrates that significantly lowered strains in the axonal direction as well as
      increased maximum principal strains are detected for anisotropic regions of the
      brain. Thus, the orientation-dependence strongly affects the response of the
      brain tissue. When anisotropy of the whole brain is taken into account,
      deformation spreads out and white matter is particularly affected. The
      introduction of local axonal orientations and fiber distribution into the
      material model is crucial to reliably address the strains occurring during an
      impact and should be considered in numerical head models for potentially more
      accurate predictions of brain injury. 

PMID- 24462380
TI  - A finite viscoelastic-plastic model for describing the uniaxial ratchetting of
      soft biological tissues.
AB  - In this paper, a phenomenological constitutive model is constructed to describe
      the uniaxial ratchetting (i.e., the cyclic accumulation of inelastic deformation)
      of soft biological tissues in the framework of finite viscoelastic-plasticity.
      The model is derived from a polyconvex elastic free energy function and addresses
      the anisotropy of cyclic deformation of the tissues by means of structural
      tensors. Ratchetting is considered by the evolution of internal variables, and
      its time-dependence is described by introducing a pseudo-potential function.
      Accordingly, all the evolution equations are formulated from the dissipation
      inequality. In numerical examples, the uniaxial monotonic stress-strain responses
      and ratchetting of some soft biological tissues, such as porcine skin, coronary
      artery layers and human knee ligaments and tendons, are predicted by the proposed
      model in the range of finite deformation. It is seen that the predicted monotonic
      stress-strain responses and uniaxial ratchetting obtained at various loading
      rates and in various loading directions are in good agreement with the
      corresponding experimental results. 

PMID- 24462381
TI  - The biomechanical properties of canine skin measured in situ by uniaxial
      extension.
AB  - INTRODUCTION: A uniaxial extension system was setup to analyze the mechanical
      properties of dog skin. MATERIAL AND METHODS: Pads were glued onto dog skin with
      constant reproducible geometrical parameters and the extension force was measured
      as a function of the extension values. Forty-one sites (82 cycling tests) were
      investigated in situ on 11 canine cadavers, half of them after surgically
      isolating the test area from the surrounding skin. Series of loading-unloading
      cycles of up to 5N or 10N or both loads were performed on each site. The elastic
      properties and the dissipative effects were characterized respectively by
      evaluating the secant Rigidity at maximum loads and the Fraction of dissipated
      energy. RESULTS: A hysteresis phenomenon, implying the need for preconditioning
      to attain equilibrium cycles, was apparent during mechanical characterization.
      Polynomial expressions were used to relate the measured Rigidities and the
      Fractions of dissipated energy with or without sample isolation. The latter were
      less affected by isolation. The ratios between the Rigidities at 5N to those at
      10N displayed non-linearity in the investigated extension range in contrary to
      the Fractions of dissipated energy. DISCUSSION/CONCLUSION: The parameters
      confirming the dissipative non-linear elastic behavior of dog skin were
      identified and the correlation between Rigidity and Fraction of dissipated energy
      on isolated and non-isolated skin samples was quantitatively determined. This
      extension setup can now be used as a "true in vivo" mapping tool to determine the
      mechanical characteristics of the skin during healing processes or during the
      study of Human skin disease with the dog as an animal model.

PMID- 24462382
TI  - Comparison of measurements of the uterus and cervix obtained by magnetic
      resonance and transabdominal ultrasound imaging to identify the brachytherapy
      target in patients with cervix cancer.
AB  - PURPOSE: To compare measurements of the uterus and cervix obtained with magnetic
      resonance imaging (MRI) and transabdominal ultrasound to determine whether
      ultrasound can identify the brachytherapy target and be used to guide conformal
      brachytherapy planning and treatment for cervix cancer. METHODS AND MATERIALS:
      Consecutive patients undergoing curative treatment with radiation therapy between
      January 2007 and March 2012 were included in the study. Intrauterine applicators
      were inserted into the uterine canal while patients were anesthetized. Images
      were obtained by MRI and transabdominal ultrasound in the longitudinal axis of
      the uterus with the applicator in treatment position. Measurements were taken at
      the anterior and posterior surface of the uterus at 2.0-cm intervals along the
      applicator, from the external os to the tip of the applicator. Data were analyzed
      using Bland Altman plots examining bias and 95% limits of agreement. RESULTS: A
      total of 192 patients contributed 1668 measurements of the cervix and uterus.
      Mean (+/- SD) differences of measurements between imaging modalities at the
      anterior and posterior uterine surface ranged from 1.5 (+/- 3.353) mm to 3.7 (+/-
      3.856) mm, and -1.46 (+/- 3.308) mm to 0.47 (+/- 3.502) mm, respectively. The
      mean differences were less than 3 mm in the cervix. The mean differences were
      less than 1.5 mm at all measurement points on the posterior surface. CONCLUSION:
      Differences in the measurements of the cervix and uterus obtained by MRI and
      ultrasound were within clinically acceptable limits. Transabdominal ultrasound
      can be substituted for MRI in defining the target volume for conformal
      brachytherapy treatment of cervix cancer.

PMID- 24462383
TI  - Stereotactic radiation therapy can safely and durably control sites of extra
      central nervous system oligoprogressive disease in anaplastic lymphoma kinase
      positive lung cancer patients receiving crizotinib.
AB  - PURPOSE: To analyze the durability and toxicity of radiotherapeutic local
      ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease
      progression in anaplastic lymphoma kinase-positive non-small cell lung cancer
      (NSCLC) patients. METHODS AND MATERIALS: Anaplastic lymphoma kinase-positive
      NSCLC patients receiving crizotinib and manifesting <= 4 discrete sites of eCNS
      progression were classified as having oligoprogressive disease (OPD). If
      subsequent progression met OPD criteria, additional courses of LAT were
      considered. Crizotinib was continued until eCNS progression was beyond OPD
      criteria or otherwise not suitable for further LAT. RESULTS: Of 38 patients, 33
      progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD
      criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3
      courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion
      control rates with radiation therapy were 100% and 86%, respectively. The 12
      month local lesion control rate with single-fraction equivalent dose >25 Gy
      versus <= 25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation
      therapy-related toxicities were observed. Median overall time taking crizotinib
      among those treated with LAT versus those who progressed but were not suitable
      for LAT was 28 versus 10.1 months, respectively. Patients continuing to take
      crizotinib for >12 months versus <= 12 months had a 2-year overall survival rate
      of 72% versus 12%, respectively (P<.0001). CONCLUSIONS: Local ablative therapy
      safely and durably eradicated sites of individual lesion progression in
      anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose
      response relationship for local lesion control was observed. The suppression of
      OPD by LAT in patients taking crizotinib allowed an extended duration of exposure
      to crizotinib, which was associated with longer overall survival.

PMID- 24462385
TI  - Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with
      intraoperative ultrasonography and supplemental transpupillary thermotherapy.
AB  - PURPOSE: To assess the impact on local tumor control of intraoperative
      ultrasonographic plaque visualization and selective application of transpupillary
      thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125
      (I-125) episcleral plaque brachytherapy (EPB). METHODS AND MATERIALS:
      Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal
      melanoma. Clinical features, dosimetric parameters, TTT treatments, and local
      tumor control outcomes were recorded. Statistical analysis was performed using
      Cox proportional hazards and Kaplan-Meier life table method. RESULTS: The study
      included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean,
      62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean,
      97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range,
      124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was
      detected in 142 cases (27%). Supplemental TTT was performed in 72 patients
      (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a
      median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local
      tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was
      associated with lower dose to the tumor base (P=.02). CONCLUSIONS: Ultrasound
      guided plaque localization of I-125 EPB is associated with excellent local tumor
      control. Detection of plaque tilt by ultrasonography at plaque removal allows
      supplemental TTT to be used in patients at potentially higher risk for local
      recurrence while sparing the majority of patients who are at low risk. Most
      patients require only 1 or 2 TTT sessions.

PMID- 24462386
TI  - Assessment of the radiation-equivalent of chemotherapy contributions in 1-phase
      radio-chemotherapy treatment of muscle-invasive bladder cancer.
AB  - PURPOSE: To estimate the radiation equivalent of the chemotherapy contribution to
      observed complete response rates in published results of 1-phase radio
      chemotherapy of muscle-invasive bladder cancer. METHODS AND MATERIALS: A standard
      logistic dose-response curve was fitted to data from radiation therapy-alone
      trials and then used as the platform from which to quantify the chemotherapy
      contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of
      chemotherapy effect were assumed (1) a fixed radiation-independent contribution
      to local control; or (2) a fixed degree of chemotherapy-induced
      radiosensitization. A combination of both mechanisms was also considered.
      RESULTS: The respective best-fit values of the independent chemotherapy-induced
      complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95%
      confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70).
      Independent chemotherapy effect was slightly favored by the analysis, and the
      derived CCR value was consistent with reports of pathologic complete response
      rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive
      bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. CONCLUSION:
      Although the data points in the analyzed radio-chemotherapy studies are widely
      dispersed (largely on account of the diverse range of chemotherapy schedules
      used), it is nonetheless possible to fit plausible-looking response curves. The
      methodology used here is based on a standard technique for analyzing dose
      response in radiation therapy-alone studies and is capable of application to
      other mixed-modality treatment combinations involving radiation therapy.

PMID- 24462384
TI  - Emotional and behavioral functioning after conformal radiation therapy for
      pediatric ependymoma.
AB  - PURPOSE: The standard of care for pediatric patients with ependymoma involves
      postoperative radiation therapy. Prior research suggests that conformal radiation
      therapy (CRT) is associated with relative sparing of cognitive and academic
      functioning, but little is known about the effect of CRT on emotional and
      behavioral functioning. METHODS AND MATERIALS: A total of 113 patients with
      pediatric ependymoma underwent CRT using photons as part of their enrollment on
      an institutional trial. Patients completed annual evaluations of neurocognitive
      functioning during the first 5 years after CRT. Emotional and behavioral
      functioning was assessed via the Child Behavior Checklist. RESULTS: Before CRT,
      emotional and behavioral functioning were commensurate with those of the
      normative population and within normal limits. After 5 years, means remained
      within normal limits but were significantly below the normative mean. Linear
      mixed models revealed a significant increase in attention problems over time.
      These problems were associated with age at diagnosis/CRT, tumor location, and
      extent of resection. A higher-than-expected incidence of school problems was
      present at all assessment points after baseline. CONCLUSIONS: The use of photon
      CRT for ependymoma is associated with relatively stable emotional and behavioral
      functioning during the first 5 years after treatment. The exception is an
      increase in attention problems. Results suggest that intervening earlier in the
      survivorship period-during the first year posttreatment-may be beneficial.

PMID- 24462387
TI  - A marker-based watershed method for X-ray image segmentation.
AB  - Digital X-ray images are the most frequent modality for both screening and
      diagnosis in hospitals. To facilitate subsequent analysis such as quantification
      and computer aided diagnosis (CAD), it is desirable to exclude image background.
      A marker-based watershed segmentation method was proposed to segment background
      of X-ray images. The method consisted of six modules: image preprocessing,
      gradient computation, marker extraction, watershed segmentation from markers,
      region merging and background extraction. One hundred clinical direct radiograph
      X-ray images were used to validate the method. Manual thresholding and multiscale
      gradient based watershed method were implemented for comparison. The proposed
      method yielded a dice coefficient of 0.964+/-0.069, which was better than that of
      the manual thresholding (0.937+/-0.119) and that of multiscale gradient based
      watershed method (0.942+/-0.098). Special means were adopted to decrease the
      computational cost, including getting rid of few pixels with highest grayscale
      via percentile, calculation of gradient magnitude through simple operations,
      decreasing the number of markers by appropriate thresholding, and merging regions
      based on simple grayscale statistics. As a result, the processing time was at
      most 6s even for a 3072*3072 image on a Pentium 4 PC with 2.4GHz CPU (4 cores)
      and 2G RAM, which was more than one time faster than that of the multiscale
      gradient based watershed method. The proposed method could be a potential tool
      for diagnosis and quantification of X-ray images. 

PMID- 24462388
TI  - Glial-derived neurotrophic factor reduces inflammation and improves delayed
      colonic transit in rat models of dextran sulfate sodium-induced colitis.
AB  - BACKGROUND: Intestinal inflammation is well known to cause gut dysmotility
      through the effects on the enteric nervous system. Glial-derived neurotrophic
      factor (GDNF) has been demonstrated to have anti-inflammatory effects and
      neuronal protective actions. The aim of this study was to investigate whether the
      GDNF could improve inflammation-induced gut dysmotility. METHODS: Recombinant
      adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in
      experimental colitis induced by dextran sulfate sodium (DSS). The disease
      activity index (DAI) and histological score were measured. Colonic transit was
      measured by using phenol red and assessed with the geometric center. PGP 9.5
      immunostaining was used to examine the number and distribution of enteric
      neurons. The expression of tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), and myeloperoxidase (MPO) activity were measured by ELISA
      assay. The expression of Akt, caspase-3, bcl-2 and PGP 9.5 was analyzed by
      western blot assay. RESULTS: A significant neuronal cell loss and a significant
      delay in colonic transit accompanied with the neuronal loss following
      inflammation were observed. GDNF prevented partially the loss of enteric neurons
      and ameliorated significantly experimental colitis and delayed colonic transit
      by, at least in part, down-regulation of TNF-alpha and IL-1beta expression,
      decrease of infiltration of leukocytes, and inhibition of neuronal cell
      apoptosis. CONCLUSIONS: GDNF reduces inflammation and improves delayed colonic
      transit in DSS-induced colitis. GDNF may be a useful therapeutic agent for the
      treatment of gut dysmotility in patients with UC.

PMID- 24462389
TI  - Lycium barbarum polysaccharide LBPF4-OL may be a new Toll-like receptor 4/MD2
      MAPK signaling pathway activator and inducer.
AB  - Recognition of the utility of the traditional Chinese medicine Lycium barbarum L.
      has been gradually increasing in Europe and the Americas. Many immunoregulation
      and antitumor effects of L. barbarum polysaccharides (LBP) have been reported,
      but its molecular mechanism is not yet clear. In this study, we reported that the
      activity of the polysaccharide LBPF4-OL, which was purified from LBP, is closely
      associated with the TLR4-MAPK signaling pathway. We found that LBPF4-OL can
      significantly induce TNF-alpha and IL-1beta production in peritoneal macrophages
      isolated from wild-type (C3H/HeN) but not TLR4-deficient mice (C3H/HeJ). We also
      determined that the proliferation of LBPF4-OL-stimulated lymphocytes from C3H/HeJ
      mice is significantly weaker than that of lymphocytes from C3H/HeN mice.
      Furthermore, through a bio-layer interferometry assay, we found that LPS but not
      LBPF4-OL can directly associate with the TLR4/MD2 molecular complex. Flow
      cytometry analysis indicated that LBPF4-OL markedly upregulates TLR4/MD2
      expression in both peritoneal macrophages and Raw264.7 cells. As its mechanism of
      action, LBPF4-OL increases the phosphorylation of p38-MAPK and inhibits the
      phosphorylation of JNK and ERK1/2, as was observed through Western blot analysis.
      These data suggest that the L. barbarum polysaccharide LBPF4-OL is a new Toll
      like receptor 4/MD2-MAPK signaling pathway activator and inducer. 

PMID- 24462390
TI  - Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial
      stress on an ovalbumin-induced murine model of asthma.
AB  - Evidence shows that psychosocial stress exacerbates asthma, but there is little
      intervention to alleviate negative effects of psychosocial stress on asthma. We
      investigated the role of icariin in anti-inflammation and anti-anxiety potential
      in a murine model combined psychosocial stress with allergic exposure. The
      results indicated that icariin administered remarkable increased activity in the
      center of the open field, reversed airway hyperresponsivenesss, reduced
      inflammatory cytokine infiltration to the lung and whole body and also in part
      recovered glucocorticoid responsiveness. Furthermore, our data also showed that
      icariin significantly inhibited increases of corticosterone and markedly
      increased glucocorticoid receptor mRNA and protein expression in the lungs of
      mice exposed to both stress and allergen. Collectively, we speculate that
      inducing glucocorticoid receptor modulation might be the potential mechanisms of
      icariin to facilitate corticosteroid responsiveness of cytokine production. 

PMID- 24462391
TI  - EMG signal morphology and kinematic parameters in essential tremor and
      Parkinson's disease patients.
AB  - The aim of this work was to differentiate patients with essential tremor from
      patients with Parkinson's disease. Electromyographic data from biceps brachii
      muscles and kinematic data from arms during isometric tension of the arms were
      measured from 17 patients with essential tremor, 35 patients with Parkinson's
      disease and 40 healthy controls. The EMG signals were divided to smaller segments
      from which histograms were calculated. The histogram shape was analysed with a
      feature dimension reduction method, the principal component analysis, and the
      shape parameters were used to differentiate between different subject groups.
      Three parameters, RMS-amplitude, sample entropy and peak frequency were
      determined from the kinematic measurements of the arms. The height and the side
      differences of the histogram were the most effective for differentiating between
      essential tremor and Parkinson's disease groups. The histogram parameters of
      patients with essential tremor were more similar to patients with Parkinson's
      disease than healthy controls. With this method it was possible to discriminate
      13/17 patients with essential tremor from 26/35 patients with Parkinson's disease
      and 14/17 patients with essential tremor from 29/40 healthy controls. The
      kinematic parameters of patients with essential tremor were closer to parameters
      of patients with Parkinson's disease compared to healthy controls. Combining EMG
      and kinematic analysis did not increase discrimination efficiency but provided
      more reliability to the discrimination of subject groups. 

PMID- 24462392
TI  - The complex role of mitochondrial metabolism in plant aluminum resistance.
AB  - The majority of soils in tropical and subtropical regions are acidic, rendering
      the soil a major limitation to plant growth and food production in many
      developing countries. High concentrations of soluble aluminum cations,
      particularly Al3+, are largely responsible for reducing root elongation and
      disrupting nutrient and water uptake. Two mechanisms, namely, the exclusion
      mechanism and tolerance mechanism, have been proposed to govern Al3+ resistance
      in plants. Both mechanisms are related to mitochondrial activity as well as to
      mitochondrial metabolism and organic acid transport. Here, we review the
      considerable progress that has been made towards developing an understanding of
      the physiological role of mitochondria in the aluminum response and discuss the
      potential for using this knowledge in next-generation engineering.

PMID- 24462393
TI  - Prognosis of hepatoid yolk sac tumor in women: what's up, Doc?
AB  - Ovarian yolk sac tumors are highly malignant germ cell tumors that commonly occur
      in young women. The hepatoid yolk sac tumor is a variant form of yolk sac tumor
      in which there has been extensive tumor differentiation to early liver tissue.
      Hepatoid differentiation is traditionally considered to signify a poor prognosis.
      This review focuses on diagnostic criteria and establishes the optimal treatment
      for patients with hepatoid yolk sac tumor. Immunohistochemical stains are useful
      for distinguishing hepatoid yolk sac tumor from the other hepatoid-appearing
      tumors. With a multidisciplinary treatment approach using platinum-based
      regimens, the outcome is similar to those of any yolk sac tumor. 

PMID- 24462394
TI  - Differential activation of parts of the latissimus dorsi with various isometric
      shoulder exercises.
AB  - As no study has examined whether the branches of the latissimus dorsi are
      activated differently in different exercises, we investigated intramuscular
      differences of components of the latissimus dorsi during various shoulder
      isometric exercises. Seventeen male subjects performed four isometric exercises:
      shoulder extension, adduction, internal rotation, and shoulder depression.
      Surface electromyography (sEMG) was used to collect data from the medial and
      lateral components of the latissimus dorsi during the isometric exercises. Two
      way repeated analysis of variance with two within-subject factors (exercise
      condition and muscle branch) was used to determine the significance of
      differences between the branches, and which branch was activated more with the
      exercise variation. The root mean squared sEMG values for the muscles were
      normalized using the modified isolation equation (%Isolation) and maximum
      voluntary isometric contraction (%MVIC). Neither the %MVIC nor %Isolation data
      differed significantly between muscle branches, while there was a significant
      difference with exercise. %MVIC was significantly higher with shoulder extension,
      compared to the other isometric exercises. There was a significant correlation
      between exercise condition and muscle branch in the %Isolation data. Shoulder
      extension and adduction and internal rotation increased %Isolation of the medial
      latissimus dorsi more than shoulder depression. Shoulder depression had the
      highest value of %Isolation of the lateral latissimus dorsi compared to the other
      isometric exercises. Comparing the medial and lateral latissimus dorsi, the
      medial component was predominantly activated with shoulder extension, adduction,
      and internal rotation, and the lateral component with shoulder depression.
      Shoulder extension is effective for activating the latissimus dorsi regardless of
      the intramuscular branch. 

PMID- 24462395
TI  - Acute heart failure diagnosis by ultrasound: new achievements and persisting
      limitations.

PMID- 24462396
TI  - Pulmonary thromboembolism due to paliperidone: report of 2 cases.
AB  - Venous thromboembolism (VTE) is serious medical condition, which might be caused
      by psychotropic medications. Previously, antipsychotic-induced VTE due to
      olanzapine, risperidone, clozapine, and amisulpiride was reported. In this
      report, we present 2 cases of paliperidone-induced VTE.

PMID- 24462397
TI  - Fourth-generation troponin I and infarct size in patients with ST-elevation
      myocardial infarction.

PMID- 24462398
TI  - Isolated rotational nystagmus may be the only clue to the early diagnosis of
      dorsolateral medullary infarction.
AB  - The medulla contains complex nervous structures related to motor, sensory,
      coordination, and visceral autonomic functions. The medullary infarctions cause
      various symptoms and signs depending on the location of the lesion. Lateral
      medullary infarction is caused by a vascular event in the territory of the
      posterior inferior cerebellar artery or the vertebral artery. We report a case of
      a patient with falling tendency and whirling sensation. He reported no facial
      drop, arm drift, slurred speech, difficulty of swallowing, or weakness of his
      limbs. The neurologic examination revealed no decreased muscle power, dysarthria,
      dysphagia, or other relevant neurologic deficits. Urgent noncontrast brain
      computed tomography detected no acute hemorrhage or ischemic lesion. On
      admission, the oculomotor examination revealed conjugated rotational nystagmus
      with clockwise direction. The magnetic resonance imaging of the brain
      demonstrated acute infarct in the medulla oblongata approximately 0.8 * 0.5 cm.
      The infarct appears bright on diffusion-weighted images (Fig.). A diagnosis of
      dorsolateral medulla infarction was established, and the patient was started on a
      therapy of 100 mg aspirin once daily. After standard therapies, the patient's
      recovery was uneventful.

PMID- 24462399
TI  - The use of isoproterenol and phenytoin to reverse torsade de pointes.
AB  - Torsade de pointes is a form of polymorphic ventricular tachycardia that differs
      from other forms of ventricular tachycardia in its morphology, precipitating
      factors, and therapeutic approach. Its recognition is of utmost importance, as
      the standard anti-arrythmic drugs not only might be ineffective in its
      termination but also may aggravate it. Herein, we report a case of antipsychotic
      induced torsade de pointes and describe the use of magnesium sulfate,
      isoproterenol, and phenytoin and their proposed mechanism of action.

PMID- 24462400
TI  - Point-of-care ultrasound diagnoses acute decompensated heart failure in the ED
      regardless of examination findings.

PMID- 24462401
TI  - Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal
      TGF-beta1 mRNA expression in gastritis patients.
AB  - OBJECTIVE: Helicobacter pylori (H. pylori) infection is the main cause of gastric
      inflammation. Regulatory T cells (Treg cells) suppress the activation and
      proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF
      beta1 was shown to be secreted in a subset of Treg cells known as 'Th3 cells'.
      These cells have not been sufficiently studied in context to H. pylori-induced
      inflammation in human gastric mucosa. In this study we therefore, aimed to
      investigate the expression of TGF-beta1 in the context of H. pylori colonization
      in chronic gastritis, to examine the relationship between it and histopathologic
      findings and to compare it with virulence factors. PATIENTS AND METHODS: Total
      RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38
      H. pylori-negative patients with gastritis. Mucosal TGF-beta1 mRNA expression in
      H. pylori-infected and uninfected gastric biopsies was determined by real-time
      PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated
      using PCR. RESULTS: TGF-beta1 mRNA expression was significantly increased in
      biopsies of H. pylori-infected patients compared to H. pylori-uninfected
      patients. There was association between virulence factors and TGF-beta1 mRNA
      expression. TGF-beta1 mRNA expression in mucosa was significantly higher in
      patients with vacA s1 and s1m1. CONCLUSIONS: TGF-beta1 may play an important role
      in the inflammatory response and promote the chronic and persistent inflammatory
      changes in the gastric. This may ultimately influence the outcome of H. pylori
      associated diseases that arise within the context of gastritis and vacA may
      suffice to induce expression of TGF-beta1 mRNA.

PMID- 24462402
TI  - Overlapping DNA methylation profile between placentas with trisomy 16 and early
      onset preeclampsia.
AB  - INTRODUCTION: Maternal preeclampsia is associated with altered placental
      development in the first trimester of pregnancy. Confined placental trisomy 16
      mosaicism (CPM16) is a genetic abnormality of the placenta that is highly
      predisposing to preeclampsia. We previously demonstrated widespread alterations
      in DNA methylation in 3rd trimester placentae associated with chromosomally
      normal early-onset preeclampsia (EOPET) and questioned whether similar changes
      would be associated with CPM16, making this condition a potential model for
      studying EOPET-associated changes early in pregnancy. METHODS: Using the Illumina
      Infinium HumanMethylation450 BeadChip, 3rd trimester CPM16 placental samples (N =
      10) were compared to gestational age matched controls, and to 1st trimester
      trisomy 16 placentae (N = 5). RESULTS: DNA methylation differences associated
      with CPM16 were identified at 2254 CpGs using stringent criteria (FDR < 0.01,
      Deltabeta > 0.15). A subset of these differences (11%; p < 0.0001) overlapped
      those observed in chromosomally normal EOPET using similarly stringent criteria
      (FDR < 0.01; Deltabeta > 0.125). Importantly, the majority of EOPET-associated
      CpGs were significantly altered (p < 0.05) in CPM16 with a similar Deltabeta
      distribution. This was true for CPM16 with (N = 5) and without (N = 5) EOPET,
      although EOPET cases showed a tendency towards larger changes. Of the shared
      CPM16/EOPET associated changes, three CpGs near two genes (ARGHEF37 and JUNB)
      were also altered in 1st trimester trisomy 16 placentae. DISCUSSION: Despite the
      limited sample size, widespread DNA methylation changes are observed in Trisomy
      16 that overlap those seen previously in chromosomally normal EOPET. Hence,
      Trisomy 16 may provide a model to study the progression of placental changes that
      occurs in EOPET across different gestational ages.

PMID- 24462403
TI  - Quantification by LC-MS(E) of outer membrane vesicle proteins of the Bexsero(r)
      vaccine.
AB  - Meningococcal disease is a major cause of morbidity and mortality worldwide. Its
      epidemiology is currently dominated by five capsular serogroups (A, B, C, W, and
      Y). While effective vaccines already exist for serogroups A, C, W and Y, except
      for under clonal outbreaks, no vaccine was available against serogroup B.
      Recently, a four component vaccine, Bexsero((r)), designed to prevent infection
      caused by this serogroup, has been approved in Europe and other Countries for use
      in individuals from two months of age and older. The active components of this
      vaccine are three recombinant proteins identified by reverse vaccinology combined
      with detergent extracted outer membrane vesicles (DOMV) prepared from a New
      Zealand epidemic strain. Considering their intrinsic complexity, we performed
      additional characterization of DOMVs on top of the standard quality control
      testing carried out for batch release. We applied the Hi3 label-free LC-MS(E)
      methodology to qualitatively and quantitatively characterize the DOMV protein
      content. We first, successfully investigated the robustness and the accuracy of
      the methodology for the DOMV characterization and we then applied it to compare
      six DOMV production lots. Around 100 proteins were quantified from each
      preparation. When classified according to their predicted cellular localization,
      about 90% of the total protein amount belongs consistently to the outer membrane
      compartment. Using nonparametric hypothesis testing and complementary log-log
      linear regression, the quantifications of a subset of 21 proteins common to all
      lots and including approximately 90% (85-92%) of the total protein amount
      quantified in any DOMV lot were found consistent across lots. The relevance of
      these results is two-fold, showing that the Hi3 quantification methodology is
      robust for a broad range of proteins and indicating that the manufacturing
      process currently used for the production of the Bexsero((r)) DOMV components is
      highly reproducible and consistent.

PMID- 24462404
TI  - Attenuated Mycoplasma bovis strains provide protection against virulent infection
      in calves.
AB  - Mycoplasma bovis is a major etiological agent of pneumonia and arthritis in
      feedlot beef cattle. To develop a novel live vaccine against M. bovis, two
      attenuated M. bovis strains, P150 and P180, were tested in calves for protection
      against challenge with the virulent M. bovis parental strain. Twenty calves were
      divided into four groups of five calves each that were designated as the P150,
      P180, positive control (PC), and negative control (NC) groups. Each calf in the
      P150 and P180 groups was immunized with 10(9)CFU of P150 or P180, respectively,
      via the nasal cavity, and the PC and NC groups received the mock inoculation.
      Baseline data were collected for 46 days post-immunization. The clinical signs
      were scored, and rectal temperatures and daily weight gain were recorded. The
      blood leukocyte count, the neutrophil ratio, and the serum levels of IgG, IgA,
      IFN-beta, and TNF-alpha were quantified using laboratory tests, and the nasal
      shedding was evaluated using microbiological methods. The P150, P180, and PC
      calves were challenged with a dose of 10(10)CFU of virulent M. bovis by
      intratracheal injection on 3 consecutive days. The calves were monitored for 25
      days post-challenge to observe changes in the baseline parameters. On day 25 post
      challenge the calves were euthanized for necropsy and analysis of tissue samples.
      The P150 and P180 immunizations caused no clinical abnormality, and did not
      affect daily weight gain. The post-inoculation neutrophil ratio and serum levels
      of IgG and IFN-beta significantly increased in the P150, P180, and PC calves,
      whereas the serum levels of IgA and TNF-alpha did not. After challenge, the PC
      group developed the typical clinical signs and pathology associated with M. Bovis
      infection, whereas immunization with P150 or P180 provided efficacious
      protection. Based on the scores for gross pathology and lung pathology, the
      protection rates of the P150 and P180 immunizations were 87.7% and 70.8%,
      respectively. The P150 attenuated strain is a promising candidate for a live
      vaccine against M. bovis infection in cattle. 

PMID- 24462405
TI  - Vaccination with Leishmania mexicana LPG induces PD-1 in CD8+ and PD-L2 in
      macrophages thereby suppressing the immune response: a model to assess vaccine
      efficacy.
AB  - Leishmania lipophosphoglycan (LPG) is a molecule that has been used as a vaccine
      candidate, with contradictory results. Since unsuccessful protection could be
      related to suppressed T cell responses, we analyzed the expression of inhibitory
      receptor PD-1 in CD8(+) and CD4(+) lymphocytes and it is ligand PD-L2 in
      macrophages of BALB/c mice immunized with various doses of Leishmania mexicana
      LPG and re-stimulated in vitro with different concentrations of LPG. Vaccination
      with LPG enhanced the expression of PD-1 in CD8(+) cells. Activation molecules
      CD137 were reduced in CD8(+) cells from vaccinated mice. In vitro re-stimulation
      enhanced PD-L2 expression in macrophages of healthy mice in a dose-dependent
      fashion. The expression of PD-1, PD-L2 and CD137 is modulated according to the
      amount of LPG used during immunization and in vitro re-stimulation. We analyzed
      the expression of these molecules in mice infected with 1*10(4) or 1*10(5)L.
      mexicana promastigotes and re-stimulated in vitro with LPG. Infection with
      1*10(5) parasites increased the PD-1 expression in CD8(+) and diminished PD-L2 in
      macrophages. When these CD8(+) cells were re-stimulated in vitro with LPG,
      simulating a second exposure to parasite antigens, PD-1 expression increased
      significantly more, in a dose dependent fashion. We conclude that CD8(+) T
      lymphocytes and macrophages express inhibition molecules according to the
      concentrations of Leishmania LPG and to the parasite load. Vaccination with
      increased amounts of LPG or infections with higher parasite numbers induces
      enhanced expression of PD-1 and functional inactivation of CD8(+) cells, which
      can have critical consequences in leishmaniasis, since these cells are crucial
      for disease control. These results call for pre-vaccination evaluations of
      potential immunogens, specifically where CD8 cells are required, since inhibiting
      molecules can be induced after certain thresholds of antigen concentrations. We
      propose that the analysis of PD-1 and PD-L2 are useful tools to monitor the
      optimal dose for vaccination candidates.

PMID- 24462406
TI  - Demographic, socio-economic and geographic determinants of seasonal influenza
      vaccine uptake in rural western Kenya, 2011.
AB  - Influenza-associated acute lower respiratory infections cause a considerable
      burden of disease in rural and urban sub-Saharan Africa communities with the
      greatest burden among children. Currently, vaccination is the best way to prevent
      influenza infection and accompanying morbidities. We examined geographic, socio
      economic and demographic factors that contributed to acceptance of childhood
      seasonal influenza vaccination among children living in a population-based
      morbidity surveillance system in rural western Kenya, where influenza vaccine was
      offered free-of-charge to children 6 months-10 years old from April to June,
      2011. We evaluated associations between maternal and household demographic
      variables, socio-economic status, and distance from home to vaccination clinics
      with family vaccination status. 7249 children from 3735 households were eligible
      for vaccination. Of these, 2675 (36.9%) were fully vaccinated, 506 (7.0%) were
      partially vaccinated and 4068 (56.1%) were not vaccinated. Children living in
      households located >5km radius from the vaccination facilities were significantly
      less likely to be vaccinated (aOR=0.70; 95% CI 0.54-0.91; p=0.007). Children with
      mothers aged 25-34 and 35-44 years were more likely to be vaccinated than
      children with mothers less than 25 years of age (aOR=1.36; 95% CI 1.15-1.62;
      p<0.001; and aOR=1.35; 95% CI 1.10-1.64; p=0.003, respectively). Finally,
      children aged 2-5 years and >5 years of age (aOR=1.38; 95% CI 1.20-1.59; p<0.001;
      and aOR=1.41; 95% CI 1.23-1.63; p<0.001, respectively) and who had a sibling
      hospitalized within the past year (aOR=1.73; 95% CI 1.40-2.14; p<0.001) were more
      likely to be vaccinated. Shorter distance from the vaccination center, older
      maternal and child age, household administrator's occupation that did not require
      them to be away from the home, and having a sibling hospitalized during the past
      year were associated with increased likelihood of vaccination against influenza
      in western Kenya. These findings should inform the design of future childhood
      seasonal influenza vaccination campaigns in rural Kenya, and perhaps elsewhere in
      Africa. 

PMID- 24462407
TI  - Effects of total glucosides of paeony on immune regulatory toll-like receptors
      TLR2 and 4 in the kidney from diabetic rats.
AB  - TLRs are a family of receptors that play a critical role in the pathogenesis of
      diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno
      regulatory activities. However, the relation between TGP and TLRs on diabetic
      nephropathy remains unknown. In this study, we examined effects of TGP on immune
      regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats.
      TGP decreased the levels of 24h urinary albumin excretion rate significantly in
      diabetic rats. Western blot analysis showed that TGP significantly inhibited the
      expression of TLR2 and 4, MyD88, p-IRAK1, NF-kappaB p65, p-IRF3, TNF-alpha and IL
      1beta. Quantitative real-time PCR analysis showed that the significantly
      increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats
      were significantly suppressed by TGP treatment. Macrophages infiltration were
      also markedly increased in the kidneys of the diabetic rats, but were
      significantly inhibited by TGP in a dose-dependent manner. These results suggest
      that TGP has protective effects on several pharmacological targets in the
      progress of diabetic nephropathy by selectively blocking TLRs activation in vivo.

PMID- 24462408
TI  - Esophageal stenosis caused by a rare entity.

PMID- 24462409
TI  - An unusual complication of a transjugular liver biopsy.

PMID- 24462411
TI  - The effect of volume loading on systemic oxygenation after bidirectional superior
      cavopulmonary anastomosis.
AB  - BACKGROUND: The unique series arrangement of the cerebral and pulmonary
      circulation in bidirectional superior cavopulmonary anastomosis (BCPA) makes the
      pulmonary blood flow dependent upon the cerebral blood flow. Until now, several
      investigators have tried to correct post-BCPA hypoxemia with various methods such
      as induced hyperventilation, the addition of carbon dioxide, and inhaled nitric
      oxide with variable success rates. METHODS: We prospectively studied 25 children
      with univentricular physiology undergoing BCPA surgery at 5 different time points
      in the preoperative (1 time point) and postoperative period (4 time points, each
      separated by at least 3 mm Hg changes in the superior vena cava [SVC] pressure).
      Intravenous fluids were administered in the postoperative period to raise the SVC
      pressure. RESULTS: The systemic arterial oxygen saturation (Sao2) increased
      significantly (p = 0.000) from a preoperative value of 80% +/- 7% to 86% +/- 7%,
      91% +/- 3% and 95% +/- 4% at SVC pressures of 9 +/- 1.6 mm Hg, 13 +/- 1.3 mm Hg,
      and 16 +/- 1.4 mm Hg, respectively, and then decreased to 94% +/- 4% at SVC
      pressure of 20 +/- 1.7 mm Hg. Systolic and diastolic blood pressure increased
      significantly and simultaneously with SVC pressure from 71 +/- 8 mm Hg and 42 +/-
      6 mm Hg to 89 +/- 11 mm Hg and 52 +/- 7 mm Hg, respectively (p = 0.000).
      CONCLUSIONS: Administration of intravenous fluids improves the SVC pressure,
      possibly due to an increase in the cerebral blood flow and the SVC flow, and thus
      raises the arterial oxygen tension (Pao2) and Sao2. Each patient has a unique SVC
      pressure where the Sao2 and the Pao2 are maximum; beyond that limit, the Sao2
      does not improve.

PMID- 24462410
TI  - A woman with melena and transfusion-dependent anemia.

PMID- 24462412
TI  - Influence of donor smoking on midterm outcomes after lung transplantation.
AB  - BACKGROUND: Lung transplantation (LTx) is significantly limited by donor organ
      shortage. Donor smoking history of more than 20 pack-years is considered an
      extended donor criterion. In this study, we retrospectively evaluated impact of
      donor smoking history and extent of smoking on midterm outcome after LTx.
      METHODS: In all, 237 LTx were performed in our institution between 2007 and 2012.
      Patients were divided into three groups, receiving lungs from 53% nonsmoking
      donors, 29% smoking donors with fewer than 20 pack-years, and 18% heavy smokers
      with more than 20 pack-years. RESULTS: Preoperative donor and recipient
      characteristics among the groups were comparable. However, donors from the heavy
      smokers group were significantly older (p < 0.001). The overall presence of
      abnormal histology (inflammation or metaplasia) in donor main bronchi samples
      increased with the extent of smoking but did not reach statistical significance
      (p = 0.211). Although metaplasia was found in significantly more donors from the
      heavy smokers group (p = 0.037), this did not translate into inferior outcomes
      for the recipients. There were no statistically significant differences in
      PaO2/FiO2 ratio after LTx, duration of mechanical ventilation (p = 0.136),
      intensive care unit stay (p = 0.133), and total postoperative hospital stay (p =
      0.322). One-year and three-year survival were comparable across all three groups
      (log rank p = 0.151). Prevalence of bronchiolitis obliterans syndrome (p =
      0.616), as well as bronchiolitis obliterans syndrome free survival (p = 0.898)
      after LTx were also comparable. CONCLUSIONS: In our experience, history and
      extent of donor smoking do not significantly affect early and midterm outcomes
      after LTx. Although this finding does not obviate the need for longer-term
      observation, donor lungs from even heavy smokers may not per se contraindicate
      LTx and may provide a valuable avenue for expanding donor organ availability.

PMID- 24462413
TI  - Thoracoscopic resection of the left atrial appendage after failed focal atrial
      tachycardia ablation.
AB  - BACKGROUND: This case series describes 3 patients with the unusual location of
      focal atrial tachycardia in the left atrial appendage who failed catheter
      ablation but were successfully treated by left atrial appendage resection by a
      totally thoracoscopic surgical technique. METHODS: In all 3 cases, left atrial
      appendage resection was carried out by video-assisted thoracoscopic surgery using
      only 3 5- to 10-mm incisions, eliminating the need for median sternotomy or
      thoracotomy. An endoscopic stapler was used to resect the left atrial appendage
      at its base, successfully eliminating the source of the patients' focal atrial
      tachycardia. RESULTS: The mean operative time was 84 minutes. All 3 patients
      tolerated the procedure without any complications and were discharged on
      postoperative day 3. At an average follow-up of 4.5 years, all patients remained
      asymptomatic and with normal ambulatory rhythm monitoring off all antiarrhythmic
      medications. CONCLUSIONS: Surgical resection of the left atrial appendage using a
      totally thoracoscopic approach is a safe and successful treatment option for
      patients who have failed endocardial catheter ablation. This novel approach
      utilizes smaller incisions and shorter operative times than the more invasive
      surgical techniques previously described in the literature.

PMID- 24462414
TI  - Right heart failure: an ischemic model and restraint therapy for treatment.
AB  - BACKGROUND: Right heart failure is poorly understood and treated. In left heart
      failure, ventricular restraint can reverse pathologic left ventricular
      remodeling. The effect of restraint in right heart failure, however, is not
      known. We hypothesize that ventricular restraint can be applied selectively to
      the right ventricle (RV) to promote RV reverse remodeling. METHODS: Right heart
      failure was induced by right coronary artery ligation in a sheep model. Eight
      weeks later, a saline-filled epicardial balloon was placed around the RV surface
      for restraint. Restraint level was defined by measuring balloon luminal pressure
      at end-diastole. Maximum balloon pressure was determined by the amount of balloon
      pressure required to decrease systemic mean arterial pressure by 10 mm Hg. We
      determined end-diastolic transmural myocardial pressure, indices of myocardial
      oxygen consumption, and RV diastolic compliance at 4 different restraint levels.
      RESULTS: After coronary ligation, RV ejection fraction (EF) decreased from
      0.574+/-0.04 to 0.362+/-0.03 (p<0.05). End-diastolic RV volume increased from
      70.8 mL/m2+/-9 to 82.2 mL/m2+/-7 (p<0.05) by magnetic resonance imaging. After
      application of restraint to the RV only, RV transmural pressure decreased
      significantly by 27%. Greater levels of restraint also improved RV EF (0.347+/
      0.06 to 0.473+/-0.05) but did not change RV end-diastolic volume. CONCLUSIONS: A
      model of ischemic right heart failure was successfully created. Selective RV
      restraint results in improved mechanical efficiency, decreased wall stress, and
      improved EF. The benefits of restraint in right heart failure warrant further
      investigation.

PMID- 24462415
TI  - Transcatheter aortic valve implantation by the left axillary approach: a single
      center experience.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an accepted
      alternative treatment for severe symptomatic aortic stenosis in high-risk and
      inoperable patients. Femoral or transapical accesses are commonly used. We report
      our initial clinical experience with TAVI using the left-axillary artery
      approach. METHODS: A single-center, retrospective study of patients undergoing
      transaxillary TAVI between January 2010 and December 2012 was performed.
      Procedural success was defined as successful device implantation with reduction
      in the mean aortic gradient and without need for conversion to open-heart
      surgery. Short-term echocardiographic follow-up was obtained in all patients.
      RESULTS: A total of 18 consecutive patients with severe aortic stenosis who were
      not candidates for surgical replacement underwent transaxillary TAVI. Mean age
      was 81.1+/-7.3 years and 14 patients (78%) were male. Median logistic European
      System for Cardiac Operative Risk Evaluation was 8.5% (range, 1.5% to 54.1%).
      Procedural success was obtained in 17 out of 18 patients (94%). There was no in
      hospital or 30-day mortality. One major bleeding complication in the form of an
      upper gastrointestinal bleeding was observed. No stroke or major vascular
      complication was reported. Postoperative implantation of a permanent pacemaker
      was performed in 7 patients (39%). At a mean follow-up of 326+/-213 days, mean
      aortic gradient was 10.8+/-4.8 mm Hg. Mean aortic valve area was 1.7+/-0.4 cm2
      and aortic insufficiency grade was mild or less in all but 1 patient, who showed
      moderate regurgitation. CONCLUSIONS: The transaxillary approach for TAVI is
      associated with high procedural success and low rates of stroke, vascular, or
      bleeding complications. This approach is an appealing alternative to the commonly
      used transfemoral and transapical TAVI.

PMID- 24462416
TI  - The frequency of BRO beta-lactamase and its relationship to antimicrobial
      susceptibility and serum resistance in Moraxella catarrhalis.
AB  - We investigated the frequency of BRO beta-lactamase and its relationship to
      antibiotic susceptibility profiles and serum susceptibility. Moraxella
      catarrhalis clinical isolates (n = 197) were collected from patients with
      respiratory tract infections in Tokyo between November 2004 and April 2005.
      Phenotypic and genotypic detection of beta-lactamases was performed. The MICs of
      6 antibiotics were determined by Etest, and the serum bactericidal assay was
      conducted by using the culture-and-spot test. Nearly all (192; 97%) of the
      clinical isolates were beta-lactamase producers; of these, 182 (95%) were bro-1
      and 10 (5%) were bro-2 positive. MIC50, MIC90, and geometric mean MICs of
      penicillin, amoxicillin, cefixime, and clarithromycin for BRO-1 isolates were
      significantly higher than for BRO-2 isolates. The frequency of intermediate and
      full serum resistance was significantly higher in BRO-1 isolates than in BRO-2
      isolates (P = 0.0056), but not BRO-negative isolates (P = 0.1333). We provide the
      first evidence that the presence of BRO-1 in M. catarrhalis is associated with
      reduced susceptibility to clarithromycin and beta-lactam antibiotics, as well as
      serum non-sensitive (intermediate and resistant). 

PMID- 24462417
TI  - Rapid and effective diagnosis of pulmonary tuberculosis with novel and sensitive
      loop-mediated isothermal amplification (LAMP) assay in clinical samples: a meta
      analysis.
AB  - In recent years, Loop-mediated isothermal amplification (LAMP) assay has been
      introduced for the diagnosis of pulmonary tuberculosis (TB). We performed the
      meta-analysis to establish the overall accuracy of LAMP assay for diagnosing
      pulmonary TB. Based on comprehensive searches of the pubmed, embase and cochrane
      databases, we identified outcome datas from all articles estimating diagnostic
      accuracy with LAMP assay until 1 October 2012. A summary estimation for
      sensitivity, specificity, diagnostic odds ratios (DOR) and the area under the
      summary ROC curve (AUC) was calculated by using the bivariate random-effects
      approach. The meta-analysis included 10 studies (1920 suspected specimens). The
      summary estimate was 80.0% (95%CI, 78.0%-83.0%) for sensitivity, 96.0% (95%CI,
      95.0%-97.0%) for specificity and 119.85/0.9633 for DOR/AUC in pulmonary TB. The
      findings in subgroup analysis were as follows: the accuracy of LAMP assay is
      higher in high quality level studies than moderate and low quality level studies.
      The pooled sensitivity for the diagnosis of pulmonary TB was 90.0% (95%CI, 86.0
      93.0%) and 75.0% (95%CI, 71.0-78.0%) for high quality level studies and moderate
      combined low quality level studies, respectively, while the specificity was 99.0%
      (95%CI, 98.0-100.0%) and 91.0% (95%CI, 88.0-94.0%). Pulmonary TB can be rapidly
      and accurately diagnosed with LAMP assay. 

PMID- 24462418
TI  - Hyperferritinemia in neonatal and infantile human parechovirus-3 infection in
      comparison with other infectious diseases.
AB  - Human parechovirus-3 (HPeV-3) has been associated with severe clinical
      manifestations in neonates and infants in the form of sepsis or hemophagocytic
      lymphohistiocytosis (HLH)-like illness. To clarify the clinical features of HPeV
      3 infection, we compared clinical signs and laboratory findings among
      enteroviruses (EVs), HPeV-3, and other infections. Participants were 26 febrile
      infants in whom EVs (n = 20) or HPeV-3 (n = 6) were isolated from throat swab or
      fecal specimens. Clinical and laboratory data were compared among EVs, HPeV-3,
      respiratory syncytial virus (RSV) infection (n = 15), and bacterial meningitis (n
      = 8) groups. Apnea was frequently seen in the HPeV-3 group although there were no
      significant differences in other clinical symptoms. Leukocyte count was
      significantly lower in the HPeV-3 group than in the EV and RSV group. Platelet
      count was significantly lower in the HPeV-3 group than in the RSV group. Serum
      ferritin levels in the HPeV-3 group (mean, 2437 ng/ml) and EV group (mean, 552
      ng/ml) were significantly higher than in the RSV group (mean 237 ng/ml; P = 0.008
      and P = 0.002, respectively). The frequency of patients with clearly high
      ferritin levels >=1000 ng/ml was comparatively higher in the HPeV-3 group (4/6)
      than the EV group (3/20) (P = 0.03). In the HPeV-3 group, ferritin levels were
      high on Days 4-5. Elevated ferritin levels, decreased leukocyte and platelet
      counts could offer diagnostic clues to HPeV-3 infection in infant. These
      laboratory findings might be associated with aberrant immune response to HPeV-3,
      which could contribute to the development of sepsis or HLH-like illness in
      neonates. 

PMID- 24462419
TI  - Clinical efficacy of roxithromycin in men with chronic prostatitis/chronic pelvic
      pain syndrome in comparison with ciprofloxacin and aceclofenac: a prospective,
      randomized, multicenter pilot trial.
AB  - Roxithromycin is effective in the treatment of intracellular organisms, including
      chlamydia and mycoplasma, and exhibits anti-inflammatory and immunomodulatory
      effects on respiratory diseases. To explore the potential therapeutic benefit of
      roxithromycin in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), this
      study compared the effect of roxithromycin with ciprofloxacin and aceclofenac. A
      total of 75 patients with CP/CPPS were randomized to three groups in open-label:
      group 1, ciprofloxacin; group 2, aceclofenac; and group 3, roxithromycin. The
      patients were treated for 4 weeks and were subsequently followed for 12 weeks.
      Changes from baseline in the total and domain scores of the NIH Chronic
      Prostatitis Symptom Index (NIH-CPSI) were evaluated. The NIH-CPSI score decreased
      in the roxithromycin, ciprofloxacin, and aceclofenac groups to a similar degree.
      The NIH-CPSI initial and 12-week total scores were 20.3 and 10.0, respectively,
      in group 1; 23.6 and 14.3, respectively, in group 2; and 21.1 and 9.8,
      respectively, in group 3. The three treatment arms did not differ significantly
      with respect to the efficiency of treatment (p > 0.05). Compared to patients in
      groups 1 and 2, group 3 patients with Category IIIb disease exhibited favorable
      results upon follow-up 12 weeks after treatment. The International Prostate
      Symptom Score (IPSS), uroflowmetry, and post-void residual volume were equivalent
      between the groups. Roxithromycin exhibits similar or favorable effects on the
      improvement of CP/CPPS compared to ciprofloxacin and aceclofenac. Roxithromycin
      could be used as a new therapeutic agent for CP/CPPS. Further study of the
      immunomodulatory action of roxithromycin in CP/CPPS is required.

PMID- 24462420
TI  - Comparison of two transport systems available in Japan (TERUMO kenkiporter II and
      BBL Port-A-Cul) for maintenance of aerobic and anaerobic bacteria.
AB  - The kenkiporter II (KP II) transport system is commonly used in many hospitals in
      Japan for transporting bacterial specimens to microbiology laboratories.
      Recently, the BBL Port-A-Cul (PAC) fluid vial became available. However, no
      reports thus far have compared the effectiveness of these two transport systems.
      We chose 4 aerobic and facultative anaerobic bacteria as well as 8 anaerobic
      organisms, and prepared three strains of each bacterium in culture media for
      placement into PAC and KP II containers. We compared the effectiveness of each
      transport system for preserving each organism at 6, 24, and 48 h after
      inoculation at room temperature. Thirty-six strains out of 12 bacteria were used
      in this study. The PAC system yielded better recovery in quantity of organisms
      than the KP II system at 6, 24 and 48 h. More strains were significantly
      recovered with the PAC system than with the KP II at 24 h (36/36 vs. 23/36, P <
      0.001) and 48 h (30/36 vs. 12/36, P < 0.001). The PAC system was better in the
      recovery of viable organisms counted at 24 and 48 h after inoculation compared
      with the KP II system. The PAC system may be recommended for the transfer of
      bacterial specimens in clinical settings. 

PMID- 24462421
TI  - Presepsin as a powerful monitoring tool for the prognosis and treatment of
      sepsis: a multicenter prospective study.
AB  - Presepsin is a protein whose levels increase specifically in the blood of
      patients with sepsis. It is proposed as a diagnostic and prognostic marker for
      assessing the degree of sepsis severity. The present multicenter prospective
      study compared the clinical utility of presepsin with other conventional sepsis
      biomarkers including procalcitonin, interleukin-6, and C-reactive protein for
      evaluating the severity of sepsis during follow-up. Patients with sepsis (n =
      103) admitted to the emergency room or intensive care unit were enrolled in this
      study and classified into 3 diagnostic groups: sepsis, severe sepsis, and septic
      shock. Blood samples were obtained from each patient on admission and after 1, 3,
      5, and 7 days. The patients were further divided into the favorable and
      unfavorable prognosis groups on the basis of several indicators of sepsis
      severity (i.e., Sequential Organ Failure Assessment score, and Acute Physiology
      and Chronic Health Evaluation II score). The patients in the favorable prognosis
      group exhibited significant decreases in all biomarker levels on days 3 and 7
      after admission. In the unfavorable prognosis group, only presepsin levels did
      not decrease significantly during follow-up. The period of antibiotics treatment
      in the unfavorable prognosis group was significantly longer than those in the
      favorable prognosis group (P < 0.05). The unfavorable prognosis group had
      significantly higher 28-day mortality than the favorable prognosis group (P <
      0.05). Therefore, the results suggest that presepsin levels correlated with the
      severity of sepsis during follow-up in comparison with other conventional sepsis
      biomarkers. 

PMID- 24462423
TI  - Microbiological and clinical characteristics in acute bacterial prostatitis
      according to lower urinary tract manipulation procedure.
AB  - We conducted a retrospective analysis of acute bacterial prostatitis (ABP)
      secondary to manipulation to document clinical features, management and
      microbiology based on the route of prior manipulation, which can be divided into
      two subgroups: transrectal and transurethral procedure. The medical records of
      158 cases compatible with a confirmed diagnosis of ABP secondary to manipulation
      from 7 urological centers between 2001 and 2012 were reviewed. When
      subcategorized according to route of prior manipulation of the lower urinary
      tract, there were distinct differences between transrectal and transurethral
      manipulation group with regard to clinical and microbiological features.
      Escherichia coli was the most common causative bacterium in both groups, but
      Pseudomonas spp. were much more dominant pathogens in the group by transurethral
      manipulation than transrectal manipulation group. The susceptibilities to second
      , third- and fourth-generation cephalosporins, amikacin, carbapenem and aztreonam
      were shown to be very low in the transurethral manipulation group. Therefore, it
      will take account the difference in antibiotic selection in the patients with ABP
      secondary to manipulation according to the manipulation route. 

PMID- 24462422
TI  - Seroprevalence of tetanus toxoid antibody and booster vaccination efficacy in
      Japanese travelers.
AB  - Tetanus can be prevented by vaccination, which is especially important for
      overseas travelers. However, despite booster vaccination every 10 years being
      recommended, most Japanese adults do not receive it in the absence of physical
      injury or overseas travel. We aimed to investigate the level of protective
      immunity against tetanus among Japanese travelers, which may provide valuable
      information for formulating booster vaccination recommendations. 113 Japanese
      travelers given tetanus toxoid were recruited. The collected samples included
      paired samples prior to and 3-5 weeks after receiving the booster vaccination.
      Travelers who did not return and those lacking sample collection at the second
      visit were excluded. Finally, 96 paired blood samples were collected. History of
      immunization against tetanus, including DPT and DT vaccines, was determined from
      interviews or immunization records. The pre-vaccination geometric mean titer for
      the 96 participants was 1.07 IU/mL; 76% had a protective antitoxin level (>0.1
      IU/mL), and 50% had a long-term protective antitoxin level (>1.0 IU/mL). Most
      participants <40 years old had protective immunity without receiving booster
      vaccination, whereas only 30.8% of those >50 years of age had protective
      immunity. Among the 23 participants without protective antitoxin levels (<0.1
      IU/mL), booster vaccination was efficient in 100% of those <40 years but in only
      28.6% of those >50 years of age. Although the tetanus antitoxin level decreases
      with age, booster vaccination helped to achieve an adequate protective antitoxin
      levels in Japanese travelers <40 years of age. Furthermore, the individuals who
      have never been vaccinated against tetanus especially in those >50 years old need
      to obtain protective immunity against tetanus according to a basic immunization
      schedule to prevent tetanus in travelers and residents of Japan. 

PMID- 24462424
TI  - High-dose regimen to achieve novel target trough concentration in teicoplanin.
AB  - In the treatment of severe MRSA infections such as endocarditis, more than 20
      mg/L of plasma trough concentration (C(min)) is recommended for teicoplanin;
      however, in the treatment of common MRSA infections, recommended C(min) remains
      more than 10 mg/L. In this study, we set C(min) as 15-30 mg/L to obtain a
      favorable clinical outcome in the treatment of common MRSA infections, and
      investigated the optimal loading regimen that achieved the target C(min) in
      patients with normal renal function. Seventy-eight patients received the high
      dose regimen A (6 mg/kg every 12-h for initial two days) and 60 patients received
      the high-dose regimen B (the first five loading doses of 10-12 mg/kg at 12-h
      intervals for initial three days, followed by 6 mg/kg once daily). The mean
      C(min) on the 4th day was 13.7 +/- 5.3 mg/L in regimen A, and 20.0 +/- 6.6 mg/L
      in regimen B (P < 0.001), and the proportion of patients achieving the 15-30 mg/L
      was 25.6% and 68.3% (P < 0.001). Clinical response at end-of treatment were 66.7%
      and 85.0% (P = 0.014). The patients of initial C(min) with >=15 mg/L had tended
      to be higher clinical response than those with <15 mg/L (80.9% vs 68.6%, P =
      0.084). There were no significant differences in the occurrence of adverse
      effects in regimen A and B (nephrotoxicity; 1.3% vs 3.3%, P = 0.413,
      hepatotoxicity; 5.1% vs 3.3%, P = 0.608). In conclusion, to obtain C(min) 15-30
      mg/L, the first five loading doses of 10-12 mg/kg at 12-h intervals was required
      in patients with normal renal function.

PMID- 24462425
TI  - Susceptibility of various oral antibacterial agents against extended spectrum
      beta-lactamase producing Escherichia coli and Klebsiella pneumoniae.
AB  - With the increase in extended spectrum beta-lactamase (ESBL)-producing bacteria
      in the community, cases are often seen in which treatment of infectious diseases
      with oral antimicrobial agents is difficult. Therefore, we measured the
      antimicrobial activities of 14 currently available oral antimicrobial agents
      against ESBL-producing Escherichia coli and Klebsiella pneumoniae. Based on the
      standard of the Clinical and Laboratory Standards Institute (CLSI), E. coli
      showed high susceptibility rates of 99.4% to faropenem (FRPM). In terms of
      fluoroquinolones, the susceptibility rate of E. coli to levofloxacin (LVFX) was
      low at 32.2%, whereas it showed a good susceptibility rate of 93.1% to
      sitafloxacin (STFX). With respect to other antimicrobial agents, susceptibility
      rates to fosfomycin (FOM) and colistin (CL) were more than 90% each, whereas
      rates of the two antimicrobial agents expected as therapeutic agents, minocycline
      (MINO) and sulfamethoxazole-trimethoprim (ST), were low at 62.4% and 44.3%,
      respectively. Based on the CLSI standard, K. pneumoniae showed high
      susceptibility rates to ceftibuten (CETB) (91.89%), LVFX (86.49%), and STFX
      (94.6%), indicating that K. pneumoniae showed higher rates than those of E. coli,
      particularly to fluoroquinolones. Comparison of susceptibility rates according to
      E. coli genotype showed that many antimicrobial agents existed to which the CTX-M
      9 group showed high susceptibility rates. However, there were many agents to
      which the CTX-M-1 group showed low susceptibility rates, particularly to CETB
      (51.1%) and LVFX (17.0%). Although there was no significant difference by
      genotype between FRPM, STFX, and FOM, a significant difference was observed
      between LVFX, MINO, and ST. Antibiotic-resistant bacteria with highly pathogenic
      strains have spread in the community, appropriate use of oral antimicrobial
      agents is required. 

PMID- 24462426
TI  - Novel assay to detect increased level of neutralizing anti-interferon gamma
      autoantibodies in non-tuberculous mycobacterial patients.
AB  - Subjects exposed to non-tuberculous mycobacterium (NTM) species do not always
      develop an active disease, which likely reflects underlying host susceptibility
      factors. Recent reports have shown that anti interferon gamma (IFN-gamma)
      neutralizing autoantibodies (IFN-gamma Ab) are associated with the development of
      disseminated NTM in patients without known evidence of immunodeficiency. The
      purpose of this study is to establish the screening method if subjects have IFN
      gamma Ab. Whole blood was obtained from patients with disseminated NTM, those
      with pulmonary NTM, and healthy controls. The neutralizing capacity to IFN-gamma
      activity was assessed as an inhibition of Signal Transducer and Activation of
      Transcription 1 (STAT-1) phosphorylation in leukocyte after stimulation with
      exogenous IFN-gamma by flow cytometer. The strength of phosphorylation was
      described as STAT1 phosphorylation index. Antigen capture assay was performed to
      measure the relative titer of Immunoglobulin-G fraction of IFN-gamma Ab. STAT1
      phosphorylation by IFN-gamma was significantly inhibited in the leukocytes from
      patients with disseminated NTM compared to that in healthy subjects, while this
      inhibition was not observed in patients with pulmonary NTM. All subjects with
      inhibited STAT1 phosphorylation had high titer of Immunoglobulin-G that reacted
      with IFN-gamma in the antigen capture assay. The measurement of STAT1
      phosphorylation index in whole blood leukocytes and antigen capture assay are
      simple and useful method for detection of anti-IFN-gamma neutralizing
      autoantibodies, and is valuable in the pathophysiological diagnosis of
      disseminated NTM patients without obvious immunodeficiency. 

PMID- 24462427
TI  - Case of keratitis caused by Streptomyces thermocarboxydus.
AB  - We describe a case of keratitis caused by Streptomyces thermocarboxydus and
      report the usefulness of molecular analysis in identifying the exact species of
      Streptomyces. A 50-year-old man was diagnosed with keratitis caused by
      Streptomyces sp. which was identified as S. thermocarboxydus by sequencing the
      16S rDNA. He had no history of trauma or systemic diseases. He was initially
      treated with topical beta-lactams and fluoroquinolones, and systemic beta-lactams
      but the keratitis did not improve. His vision improved significantly after
      topical erythromycin (5 mg/ml) and oral minocycline (200 mg/day) therapy. Our
      findings demonstrate that molecular analysis can be used to identify the exact
      Streptomyces species causing the keratitis. This then allowed us to determine the
      susceptibility of this species to different antibacterial drugs which were used
      to treat our patient successfully. 

PMID- 24462428
TI  - Moraxella lacunata infection associated with septicemia, endocarditis, and
      bilateral septic arthritis in a patient undergoing hemodialysis: a case report
      and review of the literature.
AB  - We report the first case of both endocarditis and bilateral septic arthritis in a
      patient caused by Moraxella lacunata and successful management of the infection
      with antimicrobial therapy. The route of entry leading to bacteremia may have
      been the oral cavity given the poor oral hygiene of the patient as evidenced by
      bleeding gums. We hypothesize that the bacteremia led to septic arthritis and
      mitral valve infective endocarditis. In this case report, we also review the
      literature on M. lacunata infections and conclude that this organism should be
      considered in bilateral septic arthritis in a patient with underlying heart
      abnormalities and/or with renal failure. 

PMID- 24462429
TI  - An immunocompetent child with chromosomally integrated human herpesvirus 6B
      accidentally identified during the care of Mycoplasma pneumoniae infection.
AB  - Human herpesvirus 6 (HHV-6) is the only virus known to integrate into human
      chromosomes and be transmitted from parents to offspring. Less than 1% of the
      population carries integrated HHV-6 in their genomes. Here, we report the case of
      a 9-year-old Japanese girl with an extraordinarily high copy number of HHV-6B in
      her genome. The integrated virus genome was detected by real-time polymerase
      chain reaction (PCR) in cerebrospinal fluid and serum during the treatment of
      meningoencephalitis and pneumonia caused by Mycoplasma pneumoniae infection.
      Furthermore, the HHV-6B genome was detected in hair follicle, plasma, and whole
      blood in the patient and her mother, but not in the patient's father.
      Fluorescence in situ hybridization revealed that the viral genome was integrated
      into chromosome 22. Therefore, these results emphasize the importance of
      screening for chromosomally integrated HHV-6 prior to starting unnecessary
      antiviral therapies, particularly for patients harboring HHV-6 with a high copy
      number. 

PMID- 24462430
TI  - A case of nosocomial Legionella pneumonia associated with a contaminated hospital
      cooling tower.
AB  - We report the epidemiological investigation of a nosocomial pneumonia case due to
      Legionella pneumophila linked to a contaminated hospital cooling tower in an
      immune-compromised patient. A 73-year-old female patient was diagnosed with
      nosocomial Legionella pneumonia proven by a culture of L. pneumophila serogroup 1
      from bronchoalveolar lavage fluid. Two strains isolated from the patient and two
      strains isolated from two cooling towers were found to be identical using
      repetitive-sequence-based-PCR with a 95% probability. This Legionella pneumonia
      case might be caused by aerosol from cooling towers on the roof of the hospital
      building which was contaminated by L. pneumophila. We increased up the
      temperature of hot water supply appropriately for prevention of Legionella
      breeding in an environment of patients' living. On the other hand, as the
      maintenance of cooling tower, we increased the frequency of Legionella culture
      tests from twice a year to three times a year. In addition, we introduced an
      automated disinfectants insertion machine and added one antiseptic reagent
      (BALSTER ST-40 N, Tohzai Chemical Industry Co., Ltd., Kawasaki, Japan) after this
      Legionella disease, and thereafter, we have no additional cases of Legionella
      disease or detection of Legionella spp. from the cooling tower or hot water
      supply. This case demonstrates the importance of detecting the infection source
      and carrying out environmental maintenance in cooperation with the infection
      control team. 

PMID- 24462431
TI  - Influence of prior pandemic A(H1N1)2009 virus infection on invasion of MDCK cells
      by community-associated methicillin-resistant Staphylococcus aureus.
AB  - Secondary bacterial pneumonia due to community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) has become a highly publicized cause of death
      associated with influenza. In this study, we performed the gentamicin-killing
      assay using Madin-Darby canine kidney (MDCK) cells and MRSA strains to
      investigate whether prior infection from pandemic A(H1N1)2009 virus
      (A[H1N1]pdm09) lead to increased invasion of MDCK cells by MRSA. We found that
      the invasion rate of two MRSA strains (ATCC BAA-1680 [USA 300] and ATCC BAA-1699
      [USA 100]) into intact MDCK cell monolayers was 0.29 +/- 0.15% and 0.007 +/-
      0.002%, respectively (p < 0.01, n >= 3). In addition, the relative invasion rate
      of both ATCC BAA-1680 and ATCC BAA-1699 was significantly increased by prior
      A(H1N1)pdm09 infection of MDCK monolayers from 1 +/- 0.28 to 1.38 +/- 0.02 and
      from 1 +/- 0.24 to 1.73 +/- 0.29, respectively (p < 0.01). These results indicate
      that ATCC BAA-1680 displays much stronger invasiveness of MDCK cells than ATCC
      BAA-1699, although invasion of both strains was increased by prior A(H1N1)pdm09
      infection. In conclusion, this study provided the first evidence that prior
      A(H1N1)pdm09 infection facilitates the invasion of MDCK cells by MRSA, presumably
      due to cellular injury caused by the virus. 

PMID- 24462432
TI  - Prevalence of sexually transmitted infections among healthy Korean women:
      implications of multiplex PCR pathogen detection on antibiotic therapy.
AB  - In this study, we investigated the prevalence of sexually transmitted infections
      (STIs) using multiplex real-time PCR assay in healthy Korean women. We also
      evaluated the risk factors of STIs, and compared the various factors between the
      STI-positive and the STI-negative groups. A total of 799 endocervical swab
      samples from healthy Korean women who visited our hospital for general medical
      check-ups during January 2012 to October 2012 were included. Eight STIs including
      Human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae
      (NG), Mycoplasma genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum
      (UU), Ureaplasma parvum (UP), and Trichomonas vaginalis (TV) were detected using
      Anyplex II STI-7 Detection assay Detection (Seegene, Seoul, Korea) and Hybrid
      Capture 2 High-Risk HPV DNA test (Digene Corporation, Gaithersburg, MD, USA)
      according manufacture's protocols. Ninety-seven (12.1%) subjects were positive
      for HPV. Of 393 (49.2%) subjects were infected with at least one microorganism
      and a total of 499 STIs were identified. Among the 393 STI-positive subjects, the
      proportion of single, double and triple infection was 76.3%, 20.4% and 3.3%,
      respectively. The median age of the STI-positive group (47 years, range 42-52)
      was younger than the STI-negative group (49 years, range 43-56; P < 0.001). The
      infection rate of HPV was significantly higher in the STI-positive group (15.8%,
      62/393) than the STI-negative group (8.6%, 35/406) (P = 0.002). 

PMID- 24462433
TI  - Self-reported histories of disease and vaccination against measles, mumps,
      rubella and varicella in health care personnel in Japan.
AB  - Health care personnel are required to be immune against vaccine-preventable
      diseases, such as measles, mumps, rubella, and varicella. The aim of this study
      is to evaluate the accuracy of self-reported histories of disease and vaccination
      against measles, mumps, rubella, and varicella in order to determine the immune
      status of health care personnel. A self-reported questionnaire of history of
      previous disease and vaccination against these diseases was administered to a
      total of 910 health care personnel in Shimane university hospital in Japan, whose
      results were compared with serological evidences. There were numerous subjects
      who did not remember a history of disease (greater than 33% each) and of
      vaccination (greater than 58% each). Self-reported history of disease and
      vaccination had high positive predictive value against either disease for testing
      positive for antiviral antibodies. However, a considerable number of false
      negative subjects could be found; 88.9% of subjects for measles, 89.3% for mumps,
      62.2% for rubella and 96.3% for varicella in the population who had neither a
      self-reported history of disease nor a vaccination against each disease. In
      addition, regardless of the disease in question, a negative predictive value in
      self-reported history of disease and vaccination was remarkably low. These
      results suggest that self-reported history of disease and vaccination was not
      predictive to determine the accurate immune status of health care personnel
      against measles, mumps, rubella, and varicella. A seroprevalence survey, followed
      by an adequate immunization program for susceptible subjects, is crucial to
      prevent and control infection in hospital settings. 

PMID- 24462434
TI  - Group A Streptococcus pharyngitis outbreak among university students in a judo
      club.
AB  - We report on an outbreak of Group A Streptococcus (GAS) pharyngitis among
      university students in a judo club. Eventually, 14 of total 23 club members
      developed acute pharyngitis clinically. In a span of 15 days in April 2013, 12
      students visited our hospital complaining of sore throat and high fever. All were
      men with a median age of 19.5 years (interquartile range, 18-21). The rapid
      streptococcal antigen test was positive in 3 of 4 patients (75%) without previous
      antibiotic treatment, and in 2 of 8 patients (25%) with previous antibiotic
      treatment. The definitive diagnosis of GAS pharyngitis was made by either a
      positive RADT or positive throat culture of GAS when patients had more than 2
      findings from the Centor scoring system in this study. 5 students received the
      definitive diagnosis. The throat culture results showed that 1 out of 9
      asymptomatic students was GAS-positive. The outbreak might have occurred by
      person-to-person contact while living in a dormitory and during judo training,
      which is a highly close-contact sport. However, there was also the possibility of
      oral transmission by the shared use of water bottles, although the culture from 1
      bottle was negative. Some students continued to participate in the judo club
      activities after the onset of sore throat or fever. Healthcare professionals,
      teachers, and coaches should be aware of the potential outbreaks of infectious
      diseases among university students engaged in athletic activities. Furthermore,
      it is important to educate athletes about infectious diseases. 

PMID- 24462436
TI  - A 3-year-old boy with Guillain-Barre syndrome and encephalitis associated with
      Mycoplasma pneumoniae infection.
AB  - Mycoplasma pneumoniae is a common cause of respiratory tract illness in children.
      Among the most common extrapulmonary manifestations are disorders of the central
      nervous system, including meningitis, meningoencephalitis, cerebellitis,
      polyneuropathy, acute disseminated encephalomyelitis, and Guillain-Barre
      syndrome. Guillain-Barre syndrome, also known as acute inflammatory demyelinating
      polyradiculoneuropathy, is an acute-onset, immune-mediated disorder of the
      peripheral nervous system. The central nervous system is usually intact in
      patients with Guillain-Barre syndrome. However, there have been some reports of
      an association of Guillain-Barre syndrome with central nervous system involvement
      in children. We report a 3-year-old boy with M. pneumoniae infection associated
      with Guillain-Barre syndrome and encephalitis. Both serum anti-GM1 ganglioside
      (IgG and IgM) and anti-galactocerebroside IgG antibodies were detected in our
      patient: the former in the earlier stage of the disease, and the latter in the
      later stage. We speculate that anti-GM1 ganglioside was associated more with
      encephalitis, and anti-galactocerebroside antibody was associated more with GBS
      in our case. Our patient is the youngest report of Guillain-Barre syndrome with
      central nervous system involvement, and the first report of a pediatric patient
      with associated M. pneumoniae infection. Such cases are rarely reported, but
      highlight the need for awareness of the association of the infection with
      Guillain-Barre syndrome with central nervous system involvement. 

PMID- 24462435
TI  - Surgical site infection of scrotal and inguinal lesions after urologic surgery.
AB  - To clarify the incidence of surgical site infection (SSI) after urological
      scrotal and inguinal surgical procedures and the preventive effect of
      antimicrobial prophylaxis for SSI, retrospective analysis was performed. The
      patients who underwent scrotal and inguinal operations from 2001 to 2010 were
      included in this analysis. A first or second generation cephalosporin was
      administered as antimicrobial prophylaxis just before the start of surgery and no
      additional prophylaxis was conducted. The surgery was classified into 76 (38%)
      cases with testicular sperm extraction (TESE), 72 (36%) with radical orchiectomy,
      29 (14.5%) with bilateral orchiectomy (surgical castration) and 23 (11.5%) with
      other scrotal and inguinal operations. The median age and age range were 36 years
      and 18-81 years, respectively. SSI occurred in 7 (3.5%) cases. The frequencies of
      SSI were 6.5% in the patients with urological inguinal surgery and 1.6% in those
      with scrotal surgery. The frequency of SSI in the patients with urological
      inguinal surgery was not negligible even though it is considered a clean
      operation, and further analysis is warranted to prevent SSI. 

PMID- 24462437
TI  - Clinical features, risk factors and treatment of fulminant Mycoplasma pneumoniae
      pneumonia: a review of the Japanese literature.
AB  - Mycoplasma pneumoniae (MP) is one of the most common causes of community-acquired
      pneumonia in children and young adults. Although MP sometimes causes self
      limiting pneumonia, severe and fulminant cases with hypoxia occur, but their
      clinical features have rarely been reported. This study aimed to reveal the
      clinical manifestations, risk factors, and treatment of fulminant MP pneumonia
      (MPP). Using PubMed and abstracts from the proceedings of several domestic
      Japanese academic societies, we reviewed the Japanese and English literature for
      cases of fulminant or severe MPP reported in Japan. All clinical information such
      as sex, age, underlying diseases, clinical symptoms, clinical course, laboratory
      and radiological findings, and treatment was collected and analyzed. In total, 52
      fulminant MPP cases were reported between September, 1979 and February, 2010. The
      dominant population of fulminant MPP was young adults without severe underlying
      diseases. Cough (97.3%), fever (100.0%), and dyspnea (83.3%) with diffuse
      abnormal findings in radiological examinations were noted. Antibiotics without
      anti-mycoplasmal activity were used in 32 cases (61.5%) as initial treatment
      prior to the onset of hypoxia. Anti-mycoplasmal drugs were appropriately used in
      41 cases (78.8%) after onset of respiratory failure with steroids (23 cases,
      45.1%) and effective. The majority of patients improved within 3-5 days after
      steroid administration. There were only 2 fatal cases. Although this small
      retrospective study did not reveal the apparent risk factors of fulminant MPP,
      initial inappropriate use of antibiotics may be a risk factor, and early
      administration of appropriate anti-mycoplasmal drugs with steroids as a cellular
      immune suppressor is required. 

PMID- 24462438
TI  - Colonization of an acid resistant Kingella denitrificans in the stomach may
      contribute to gastric dysbiosis by Helicobacter pylori.
AB  - In the stomach of a gastric ulcer patient who had been administered an anti-acid,
      a gram-negative and urease-negative bacillus similar in size to Helicobacter
      pylori was infected together with H. pylori. According to biochemical test and
      16S rRNA gene analysis, the urease-negative bacterium was identified as Kingella
      denitrificans, a human nasopharyngeal commensal. In contrast to the standard
      strain of K. denitrificans, the isolate showed catalase activity, did not produce
      acid from glucose, and exhibited acid tolerance. Acid tolerance of H. pylori was
      increased by cocultivation with the K. denitrificans isolate, but not with other
      isolates of K. denitrificans. Disruption of physiological and immunological niche
      by dysbiotic colonization of bacterium may provide pathological attributes to
      human stomach. Collectively, a careful administration of anti-acids to the
      elderly, especially those with atrophic gastritis, is necessary to avoid
      repression of the gastric barrier to bacteria.

PMID- 24462439
TI  - Infective endocarditis and meningitis due to Scedosporium prolificans in a renal
      transplant recipient.
AB  - Scedosporium prolificans is a ubiquitous filamentous fungi that may cause
      disseminated diseases in neutropenic patients with hematological malignancies. We
      report a fatal case of renal transplant recipient who developed both infective
      endocarditis and meningitis due to S. prolificans during treatment with
      micafungin and itraconazole for chronic necrotizing aspergillosis. Breakthrough
      Scedosporium infection should be considered among differential diagnosis of
      invasive fungal diseases in patients with renal transplant recipients receiving
      antifungal agents. 

PMID- 24462440
TI  - Staphylococcal endocarditis as the first manifestation of heritable protein S
      deficiency in childhood.
AB  - A 12-year-old Japanese girl developed infective endocarditis and central nervous
      system disease. The previously healthy girl showed altered consciousness and
      abnormal behaviors along with the classical signs of septic emboli.
      Staphylococcus aureus was isolated from peripheral blood, but not, the
      pleocytotic cerebrospinal fluid. Diagnostic imaging studies revealed a vegetative
      structure in the morphologically normal heart, and multiple thromboembolisms in
      the brain and spleen. Low plasma activity of protein S (12%) and thrombophilic
      family history allowed the genetic study, demonstrating that she carried a
      heterozygous mutation of PROS1 (exon 13; 1689C > T, p.R474C). Surgical
      intervention of the thrombotic fibrous organization and subsequent anticoagulant
      therapy successfully managed the disease. There are no reports of infective
      endocarditis in childhood occurring as the first presentation of heritable
      thrombophilia. Protein S deficiency might be a risk factor for the development or
      exacerbation of infective endocarditis in children having no pre-existing heart
      disease. 

PMID- 24462441
TI  - Serial quantification of procalcitonin (PCT) predicts clinical outcome and
      prognosis in patients with community-acquired pneumonia (CAP).
AB  - Procalcitonin (PCT), a calcitonin precursor, is commonly measured in the setting
      of community-acquired pneumonia (CAP). However, the clinical significance of
      serial PCT changes has not been established. We conducted a prospective
      observational study of 122 patients with CAP. Thirty-day mortality was the
      primary endpoint. Secondary endpoints included: (1) initial treatment failure,
      (2) 30-day mortality and/or initial treatment failure, and (3) intensive care
      unit (ICU) admission. In subgroup analysis, we classified patients into
      pneumococcal pneumonia and non-pneumococcal pneumonia groups. The baseline
      frequency of 30-day mortality was 10.7%. Increases in serum PCT levels from
      admission to Day 3 were observed with statistically higher frequency in patients
      with 30-day mortality (P = 0.002). For secondary endpoints, only the 30-day
      mortality and/or initial treatment failure group was statistically significant (P
      = 0.007). Subgroup analysis revealed statistically significant changes in the non
      pneumococcal pneumonia group (N = 85) across several endpoints, including 30-day
      mortality (P = 0.001), initial treatment failure (P = 0.013), and 30-day
      mortality and/or initial treatment failure (P < 0.001). No significant changes in
      endpoint measurements were found in the pneumococcal pneumonia group (N = 28).
      Interestingly, serum PCT levels at the time of diagnosis were higher in patients
      with pneumococcal pneumonia than those with non-pneumococcal pneumonia (P =
      0.006), and this positively correlated with disease severity scores for all
      patients (PCT vs. PSI: R = 0.380, P < 0.001; PCT vs. A-DROP: R = 0.422, P <
      0.001) and for non-pneumococcal pneumonia (PCT vs. PSI: R = 0.468, P < 0.001; PCT
      vs. A-DROP: R = 0.448, P < 0.001), but not for pneumococcal pneumonia. In
      conclusion, serial quantification of PCT can predict clinical outcomes for
      patients with CAP.

PMID- 24462442
TI  - A multicenter, prospective evaluation of quality of care and mortality in Japan
      based on the Surviving Sepsis Campaign guidelines.
AB  - To elucidate the standard Surviving Sepsis Campaign (SSC) guidelines-based
      quality of care and mortality related to severe sepsis in Japan, we conducted a
      multicenter, prospective, observational study using a new web-based database
      between June 1, 2010, and December 31, 2011. A total of 1104 patients with severe
      sepsis were enrolled from 39 Japanese emergency and critical care centers. All
      cause hospital mortality was 29.3% in patients with severe sepsis and 40.7% in
      patients with septic shock. Pulmonary, renal, hepatic, and hematological
      dysfunctions were associated with significantly higher mortality, and
      hematological dysfunction, especially coagulopathy, was associated with the
      highest odds ratio for mortality. Compliance with severe sepsis bundles in our
      study was generally low compared with that in a previous international sepsis
      registry study, and glycemic control was associated with lowest odds ratio for
      mortality. Despite higher complication rates of multiple organ dysfunction
      syndrome and low compliance with severe sepsis bundles on the whole, mortality in
      our study was similar to that in the international sepsis registry study. From
      these results, we concluded that our prospective multicenter study was successful
      in evaluating SSC guidelines-based standard quality of care and mortality related
      to severe sepsis in Japan. Although mortality in Japan was equivalent to that
      reported worldwide in the above-mentioned international sepsis registry study,
      compliance with severe sepsis bundles was low. Thus, there is scope for
      improvement in the initial treatment of severe sepsis and septic shock in
      Japanese emergency and critical care centers. 

PMID- 24462443
TI  - Efficacy of aerosolized liposomal amphotericin B against murine invasive
      pulmonary mucormycosis.
AB  - Invasive pulmonary mucormycosis is a life-threatening fungal infection
      encountered in immunocompromised patients. An intravenous high-dose lipid
      formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the
      recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not
      been evaluated. We evaluated the efficacy of inhaled aerosolized L-AMB in murine
      invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with
      cortisone acetate and cyclophosphamide and challenged on day 0 with 1 * 106
      conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were
      assigned to one of the following 3 treatment groups: (i) control, (ii) treatment
      only (aerosolized L-AMB from day 1-5 after challenge), and (iii) prophylaxis
      followed by treatment (aerosolized L-AMB from day -2 to 5 before and after
      challenge). Survival was monitored until 12 days after challenge. For fungal
      burden and histopathological examination, mice were sacrificed 4 h after
      treatment on day 3. Numbers of colony-forming units per lung were calculated. To
      study the distribution of AMB after inhalation of L-AMB, immunohistochemical
      studies using AMB antibody were performed. Aerosolized L-AMB significantly
      improved survival rate and decreased fungal burden compared with control group,
      and histopathology findings were superior to those of control group. However, no
      significant differences were detected between the treatment-only and prophylaxis
      followed by treatment groups. Immunohistochemical analysis showed that L-AMB was
      promptly distributed in lung tissue after inhalation therapy. Aerosolized L-AMB
      showed modest efficacy against R. oryzae infection in mice treated after fungal
      challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal
      model.

PMID- 24462444
TI  - ExoS of Pseudomonas aeruginosa binds to a human KIF7 to induce cytotoxicity in
      cultured human bronchial epithelial cells.
AB  - The lungs are a major site of Pseudomonas aeruginosa infection in patients with
      compromised immune systems. P. aeruginosa secretes a number of toxins by a type
      III secretion system, and these are important in virulence. One of these toxins,
      ExoS can induce a cytotoxic effect and is associated with the ability to produce
      lung damage. ExoS is a bifunctional toxin, with N-terminal GTPase-activating
      protein (GAP) activity and a C-terminal ADP ribosyl transferase (ADPRT) domain.
      Although these two domains have numerous potential cellular targets, the overall
      mechanism of ExoS-induced cytotoxicity remains unclear. We carried out a yeast
      two-hybrid screen using the ExoS truncation mutant ExoSDelta (residue 1-388),
      which lacks the 14-3-3 binding site in the ADPRT domain, to identify unknown
      cellular targets associated with ExoS-induced cytotoxicity. We identified the
      mammalian factor, kinesin family member 7 (KIF7), which is involved in Hedgehog
      signaling, as a binding partner for ExoSDeltaC2. A pull-down assay revealed that
      ExoS bound to the truncated KIF7 gene encoding the N-terminal domain (residues 1
      109) of KIF7. Yeast two-hybrid analysis showed that the ADPRT domain (residues
      234-354) of ExoS bound to the truncated KIF7. Furthermore, exoS gene expression
      and silencing the expression of KIF7 both caused significant cytotoxicity in
      cultured human bronchial epithelial cells (BEAS-2B). Taken together, our results
      suggest that ExoS could induce cytotoxicity in BEAS-2B cells by interacting with
      KIF7. 

PMID- 24462445
TI  - Clinical courses and outcomes of hospitalized adult patients with seasonal
      influenza in Korea, 2011-2012: Hospital-based Influenza Morbidity & Mortality
      (HIMM) surveillance.
AB  - Influenza is an acute respiratory illness, which can be accompanied by
      complications such as pneumonia. This study was conducted to survey the clinical
      courses and outcomes of hospitalized adult patients with laboratory-confirmed
      seasonal influenza. A prospective case-control study was performed in adult
      influenza patients who were admitted to hospitals participating in the Hospital
      based Influenza Morbidity and Mortality (HIMM) surveillance system in Korea from
      October 2011 to May 2012. Cases with complicated influenza were compared to those
      without complications. A total of 123 (5.6%) patients among 2184 laboratory
      confirmed adult influenza patients were hospitalized during the 2011-2012
      influenza epidemic season. Forty (32.5%) experienced 50 complication episodes.
      Age older than 60 years (P < 0.01), male sex (P = 0.04), diabetes (P < 0.01),
      chronic cardiovascular disease (P < 0.01) and neuromuscular disease (P = 0.02)
      were significantly related to development of complications in univariate
      analysis. Multivariate logistic regression analysis revealed that diabetes (odds
      ratio [OR] 3.63, 95% confidence interval [CI] 1.15-11.51, P = 0.02) was an
      independent risk factor for complicated seasonal influenza. C-reactive protein
      (CRP) was discriminative between complicated and uncomplicated influenza (cutoff
      value 13 mg/L, sensitivity 70%, specificity 74%). Complicated patients received
      antibiotics more frequently (P < 0.01) with longer hospital stays (P = 0.01). In
      conclusion, diabetic patients are at great risk for complicated influenza, and
      CRP would be useful to predicting complication. Therefore, early interventions
      such as antiviral therapy should be considered for high risk patients with
      diabetes, especially those with increased serum CRP level. 

PMID- 24462446
TI  - Serotype 35B Streptococcus pneumoniae, Japan, 2002-2012.
AB  - Among 641 pneumococcal isolates recovered from 2002 to 2012 in Japan, 19 (3.0%)
      were serotype 35B. Twelve of the 19 were ST558 (single-locus variant of Utah35B
      24-ST377) and seven were ST2755. Continuous monitoring of serotypes and their
      clonal association is important, especially in Japan where PCV7 was licensed only
      in 2010. 

PMID- 24462448
TI  - Are MMSE and HDS-R neuropsychological tests adequate for screening HIV-associated
      neurocognitive disorders?
AB  - HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in
      patients with HIV-1 infection. There are currently no standardized tests for
      screening HAND in such patients. The sensitivity of the cognitive function tests
      routinely used in clinical practice, such as the Mini-Mental State Examination
      and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even
      in patients with clear abnormal behavior. We report a 41-year-old man with HIV
      associated dementia, the most severe form of HAND, in whom the simplified methods
      did not show abnormal results, and a comprehensive battery of neuropsychological
      tests which covering several cognitive domains was needed to detect cognitive
      impairment. 

PMID- 24462447
TI  - Mycobacterium tuberculosis infection in cancer patients at a tertiary care cancer
      center in Japan.
AB  - The characteristics of active tuberculosis in cancer patients in Japan and the
      effects of this infection on cancer treatment have not yet been clarified. The
      records of all consecutive patients with microbiologically documented
      Mycobacterium tuberculosis infection diagnosed between September 2002 and March
      2008 at Shizuoka cancer center (a 557-bed tertiary care cancer center in Japan)
      were reviewed. There were 24 cancer patients with active tuberculosis during the
      study period. Of these, 23 had solid-organ tumors, and the most common site of
      the underlying malignancy was the lung. Most of the patients had pulmonary
      tuberculosis. Among 15 patients followed up for more than 2 months prior to the
      diagnosis of pulmonary tuberculosis, 12 had healed scars suggestive of old
      tuberculosis lesions, as shown by chest imaging obtained at the time of the
      initial evaluation. Discontinuation of cancer therapy or more than a month's
      delay in surgery occurred in 10 patients with pulmonary tuberculosis. Development
      of active tuberculosis can delay cancer treatment in Japanese centers. Cancer
      patients with scars suggestive of old tuberculosis disease lesions as shown by
      chest imaging should be screened for active tuberculosis and carefully followed
      up. In some cases, prophylactic treatment should be considered. 

PMID- 24462449
TI  - Cefazolin therapy for methicillin-susceptible Staphylococcus aureus bacteremia in
      Japan.
AB  - This is a retrospective cohort study of patients who were treated with cefazolin
      for methicillin-susceptible Staphylococcus aureus bacteremia, at Tokyo Women's
      Medical University Hospital between January 2006 and December 2010. During the
      study period, 84/140 (60%) patients received cefazolin (mean age, 54 years;
      range, 0-94 years, male patients 64%). Of these, 60/84 (71%) cases were hospital
      acquired infections, 55/84 (65%) had heart disease, and 19/84 (23%) had moderate
      to severe heart failure (New York Heart Association class III/IV). The treatment
      failure rate at 12 weeks was 35% (n = 29). All-cause mortality were 15% (n = 13)
      after 12 weeks and 21% (n = 18) after a year. Secondary endocarditis and
      neurological events were observed in 10% (n = 8) and 2% (n = 2). Moderate to
      severe heart failure and retained intravascular devices were associated with
      treatment failure at 12 weeks by multivariate analysis (P < 0.01, P = 0.018). Our
      results suggest that hospital-acquired methicillin-susceptible S. aureus
      bacteremia can cause severe complications in patients with moderate to severe
      heart failure who retain their intravascular devices. Both effective
      antimicrobial therapy and removal of infected foci are essential for S. aureus
      bacteremia treatments.

PMID- 24462450
TI  - One-week staged bilateral total knee arthroplasty protocol: a safety comparison
      of intended and completed surgeries.
AB  - The number of patients requiring bilateral total knee arthroplasty (TKA) is
      expected to grow rapidly. While some trials have compared staged with
      simultaneous TKA, no literature characterizes the subset of staged TKA patients
      who cancel their second surgery. In this study, we report on the safety and
      utility of a one-week staged TKA protocol in a series of 145 patients who
      registered to undergo staged bilateral total knee arthroplasty one week apart.
      Among these patients, we identify a significantly higher complication rate and
      comorbidity status among patients who do not proceed to a second TKA. This
      finding identifies a potential advantage of a staged protocol over simultaneous
      bilateral TKA in not subjecting higher-risk patients to a second physiologic
      insult of a contralateral TKA. 

PMID- 24462451
TI  - Extensor mechanism reconstruction with achilles tendon allograft in TKA: results
      of an abbreviate rehabilitation protocol.
AB  - Various treatment alternatives address extensor mechanism failure after total
      knee arthroplasty. We present the results of a protocol utilizing Achilles tendon
      allograft followed by an abbreviated immobilization program to treat extensor
      mechanism disruptions after TKA in 29 knees (27 patients). Failed reconstruction
      was defined as mechanical allograft failure requiring re-intervention, extension
      lag >30 degrees , recurrent falls, regression to a lower ambulatory status, and
      revision due to infection. With mean follow-up of 3.5 years, seventeen cases
      (58.6%) had satisfactory results, eleven cases (37.9%) were considered failures,
      and one case was lost to follow-up. Among failures, eight (27.5%) underwent
      reoperation with four (13.8%) due to late infections. Our observational data
      suggest that 1) a shortened immobilization protocol yields less favorable results
      than expected, and 2) continuous monitoring of patients who had allograft
      reconstruction for possible development of late infection is recommended.

PMID- 24462452
TI  - Spinal motor neurite outgrowth over glial scar inhibitors is enhanced by
      coculture with bone marrow stromal cells.
AB  - BACKGROUND CONTEXT: Transplantation of bone marrow cells into spinal cord lesions
      promotes functional recovery in animal models, and recent clinical trials suggest
      possible recovery also in humans. The mechanisms responsible for these
      improvements are still unclear. PURPOSE: To characterize spinal cord motor
      neurite interactions with human bone marrow stromal cells (MSCs) in an in vitro
      model of spinal cord injury (SCI). STUDY DESIGN/SETTING: Previously, we have
      reported that human MSCs promote the growth of extending sensory neurites from
      dorsal root ganglia (DRG), in the presence of some of the molecules present in
      the glial scar, which are attributed with inhibiting axonal regeneration after
      SCI. We have adapted and optimized this system replacing the DRG with a spinal
      cord culture to produce a central nervous system (CNS) model, which is more
      relevant to the SCI situation. METHODS: We have developed and characterized a
      novel spinal cord culture system. Human MSCs were cocultured with spinal motor
      neurites in substrate choice assays containing glial scar-associated inhibitors
      of nerve growth. In separate experiments, MSC-conditioned media were analyzed and
      added to spinal motor neurites in substrate choice assays. RESULTS: As has been
      reported previously with DRG, substrate-bound neurocan and Nogo-A repelled spinal
      neuronal adhesion and neurite outgrowth, but these inhibitory effects were
      abrogated in MSC/spinal cord cocultures. However, unlike DRG, spinal neuronal
      bodies and neurites showed no inhibition to substrates of myelin-associated
      glycoprotein. In addition, the MSC secretome contained numerous neurotrophic
      factors that stimulated spinal neurite outgrowth, but these were not sufficient
      stimuli to promote spinal neurite extension over inhibitory concentrations of
      neurocan or Nogo-A. CONCLUSIONS: These findings provide novel insight into how
      MSC transplantation may promote regeneration and functional recovery in animal
      models of SCI and in the clinic, especially in the chronic situation in which
      glial scars (and associated neural inhibitors) are well established. In addition,
      we have confirmed that this CNS model predominantly comprises motor neurons via
      immunocytochemical characterization. We hope that this model may be used in
      future research to test various other potential interventions for spinal injury
      or disease states.

PMID- 24462454
TI  - Three-dimensional cell culture technique and pathophysiology.
AB  - Three-dimensional (3D) tissue constructs consisting of human cells have opened a
      new avenue for tissue engineering, pharmaceutical and pathophysiological
      applications, and have great potential to estimate the dynamic pharmacological
      effects of drug candidates, metastasis processes of cancer cells, and toxicity
      expression of nano-materials, as a 3D-human tissue model instead of in vivo
      animal experiments. However, most 3D-cellular constructs are a cell spheroid,
      which is a heterogeneous aggregation, and thus the reconstruction of the delicate
      and precise 3D-location of multiple types of cells is almost impossible. In
      recent years, various novel technologies to develop complex 3D-human tissues
      including blood and lymph capillary networks have demonstrated that physiological
      human tissue responses can be replicated in the nano/micro-meter ranges. Here, we
      provide a brief overview on current 3D-tissue fabrication technologies and their
      biomedical applications. 3D-human tissue models will be a powerful technique for
      pathophysiological applications. 

PMID- 24462455
TI  - Human pathological basis of blood vessels and stromal tissue for nanotechnology.
AB  - The recent development of nanotechnology has already produced clinically
      applicable "nanodrugs," which are largely dependent on a novel concept for the
      drug delivery system. Thus the elucidation of local pharmacokinetics of nanodrugs
      is indispensable for the further development of nanomedicine; however, the
      detailed pathophysiology associated with nano-sized materials especially in
      pathologic lesions has not been well-described. In this review article, the
      microscopic appearance of vascular pericytes in addition to endothelial cells is
      discussed in the normal state and also in several pathological conditions which
      could be the major targets for nanomedicine. Moreover, the role of stromal tissue
      including myofibroblasts is also focused on, as well as inflammatory cells.
      Finally, the significance of disease-specific tissue structure in the
      establishment of personalized nanomedicine is discussed. 

PMID- 24462456
TI  - Insights into the role of components of the tumor microenvironment in oral
      carcinoma call for new therapeutic approaches.
AB  - The research on oral cancer has focused mainly on the cancer cells, their genetic
      changes and consequent phenotypic modifications. However, it is increasingly
      clear that the tumor microenvironment (TME) has been shown to be in a dynamic
      state of inter-relations with the cancer cells. The TME contains a variety of
      components including the non-cancerous cells (i.e., immune cells, resident
      fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers
      (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth
      factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is
      considered a part of the cancerous tissue and the functionality of its key
      components constitutes the setting on which the hallmarks of the cancer cells can
      evolve. Therefore, in terms of controlling a malignancy, one should control the
      growth, invasion and spread of the cancer cells through modifications in the TME
      components. This mini review focuses on the TME as a diagnostic approach and
      reports the recent insights into the role of different TME key components [such
      as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells,
      angiogenesis, stromal matrix molecules and proteases] in the molecular biology of
      oral carcinoma. Furthermore, the impact of TME components on clinical outcomes
      and the concomitant need for development of new therapeutic approaches will be
      discussed. 

PMID- 24462453
TI  - Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in
      the central nervous system.
AB  - The physiology of the vasculature in the central nervous system (CNS), which
      includes the blood-brain barrier (BBB) and other factors, complicates the
      delivery of most drugs to the brain. Different methods have been used to bypass
      the BBB, but they have limitations such as being invasive, non-targeted or
      requiring the formulation of new drugs. Focused ultrasound (FUS), when combined
      with circulating microbubbles, is a noninvasive method to locally and transiently
      disrupt the BBB at discrete targets. This review provides insight on the current
      status of this unique drug delivery technique, experience in preclinical models,
      and potential for clinical translation. If translated to humans, this method
      would offer a flexible means to target therapeutics to desired points or volumes
      in the brain, and enable the whole arsenal of drugs in the CNS that are currently
      prevented by the BBB. 

PMID- 24462457
TI  - Myosin 1e is a component of the invadosome core that contributes to regulation of
      invadosome dynamics.
AB  - Myosin 1e (myo1e) is an actin-based motor protein that has been implicated in
      cell adhesion and migration. We examined the role of myo1e in invadosomes, actin
      rich adhesion structures that are important for degradation and invasion of the
      extracellular matrix. RSV-transformed BHK-21 cells, which readily form
      invadosomes and invadosome rosettes, were used as the experimental model. Myo1e
      localization to the actin-rich core of invadosomes required the proline-rich Tail
      Homology 2 (TH2) domain. During invadosome rosette expansion, we observed myo1e
      recruitment to newly forming invadosomes via Tail Homology 1 (TH1)-dependent
      interactions with the plasma membrane, where it preceded actin and paxillin.
      Dominant-negative inhibition of myo1e resulted in mislocalized invadosome
      formation, usually at the center of the rosette. We propose that TH2 domain of
      myo1e provides the key signal for localization to invadosomes, while TH1 domain
      interactions facilitate myo1e targeting to the plasma membrane-proximal locations
      within the rosettes. Myo1e may then act as a scaffold, linking the plasma
      membrane with the actin cytoskeleton and helping direct new invadosome formation
      to the periphery of the rosette. 

PMID- 24462458
TI  - Dicoumarol sensitizes renal cell carcinoma Caki cells to TRAIL-induced apoptosis
      through down-regulation of Bcl-2, Mcl-1 and c-FLIP in a NQO1-independent manner.
AB  - In the study, we investigated the effect of dicoumarol, an anti-coagulant agent
      with the inhibitory activity of NAD(P)H quinone oxidoreductase 1 (NQO1), on TRAIL
      induced apoptosis in renal cancer cell. Combined treatment with dicoumarol and
      TRAIL significantly induced apoptosis in various human renal carcinoma cells
      including Caki, ACHN, and A498, but not in normal human skin fibroblasts (HSF)
      and mouse kidney cells (TMCK-1). When we elucidated the relevance of NQO1 in
      dicoumarol plus TRAIL-mediated apoptosis, both ES936 (a NQO1 inhibitor) and
      knockdown of NQO1 with siRNA had no effect on TRAIL-mediated apoptosis,
      suggesting that the stimulating effect of dicoumarol on TRAIL-mediated apoptosis
      is independent of NQO1 activity. We found that dicoumarol transcriptionally down
      regulated Bcl-2 expression via inhibition of NF-kappaB and CREB activity, whereas
      it down-regulated Mcl-1 and c-FLIP expression at the post-translational level.
      Overexpression of Bcl-2, Mcl-1, or c-FLIP overcame the dicoumarol plus TRAIL
      induced apoptosis, indicating that down-regualtion of these anti-apoptotic
      proteins may critically contribute to the sensitizing effect of dicoumarol on
      TRAIL-mediated apoptosis. 

PMID- 24462459
TI  - Progesterone increases ex vivo testosterone production and decreases the
      expression of progestin receptors and steroidogenic enzymes in the fathead minnow
      (Pimephales promelas) ovary.
AB  - Progesterone (P4) is a metabolic precursor for a number of steroids, including
      estrogens and androgens. P4 also has diverse roles within the vertebrate ovary
      that include oocyte growth and development. The objectives of this study were to
      measure the effects of P4 on testosterone (T) and 17beta-estradiol (E2)
      production in the fathead minnow (FHM) ovary and on the mRNA abundance of
      transcripts involved in steroidogenesis and steroid receptor signaling. Ovary
      explants were treated with P4 (10(-6)M) for 6 and 12h. P4 administration
      significantly increased T production ~3-fold at both 6 and 12h, whereas E2
      production was not affected, consistent with the hypothesis that excess P4 is not
      converted to terminal estrogens in the mature ovary. Nuclear progesterone
      receptor mRNA was decreased at 6h and membrane progesterone receptor gamma-2 mRNA
      was significantly down-regulated at both 6 and 12h; however there was no change
      in membrane progesterone receptor alpha or beta mRNA levels. Androgen receptor
      (ar) and estrogen receptor 2a (esr2a) mRNA were significantly reduced at 6h with
      P4 treatment, but there was no change in esr2b mRNA at either time point.
      Transcripts for enzymes in the steroid pathway (star, hsd11b2) were significantly
      lower at 6h compared to controls, whereas cyp17a and cyp19a mRNA abundance did
      not change with treatments at either time point. These data suggest that P4
      incubation can lead to increased T production in the FHM ovary without a
      concomitant change in E2, and that the membrane bound progestin receptors are
      differentially regulated by P4 in the teleost ovary. As environmental progestins
      have received increased attention due to their suspected role as endocrine
      disruptors, mechanistic data on the role of exogenous P4 treatments in the male
      and female gonad is warranted. 

PMID- 24462460
TI  - Cerebral venous thrombosis: clinical features, risk factors, and long-term
      outcome in a Tunisian cohort.
AB  - BACKGROUND: Data from African countries regarding diagnosis, prognosis,
      management, and outcome of patients with cerebral venous thrombosis (CVT) are
      limited. The aim of the present study is to characterize clinical presentation,
      predisposing factors, neuroimaging findings, and outcomes of the disease in the
      Tunisian population. METHODS: This is a prospective study including patients
      referred to the Neurology Department of the Military Hospital of Tunis between
      January 2009 and December 2012. The diagnosis of CVT was confirmed in all
      patients using magnetic resonance imaging and magnetic resonance venography. The
      demographic, clinical, radiological, and outcome data were recorded and analyzed.
      Median follow-up was 16 months (range 6 months to 4 years). Primary outcome was
      death or dependency as assessed by modified Rankin score more than 2 at the end
      of follow-up. RESULTS: This study included 41 patients with CVT. Mean age was
      41.24 years, predominantly women (68%). The mode of onset was acute in 10
      patients (24%), subacute in 26 (64%), and chronic in 5 (12%). The most common
      presenting features were headache, observed in 83% of the patients, followed by
      seizures, focal motor deficits, papilledema, and mental status changes. Lateral
      (56%) and superior longitudinal (51%) sinuses were the most commonly involved.
      Multiple sinuses were involved in 46% of cases. Nineteen patients (46%) had a D
      dimer level more than 500 ng/mL. Major causes of CVT were thrombophilia (56%),
      either genetic or acquired, obstetric and gynecological (50%), and septic (34%).
      Outcome was favorable in 83% of patients. At the end of follow-up, 32 patients
      (78%) had complete recovery (modified Rankin Scale [mRs] score 0-1), 2 (5%) had
      partial recovery (mRs score 2), and 4 (10%) were dependent (mRs score 3-5). One
      patient (2.5%) had a recurrent sinus thrombosis. CONCLUSIONS: Our Tunisian
      population presented distinct risk factors profile with high frequency of
      thrombophilia, infections, and postpartum state. Oral contraceptive use is not a
      major risk factor in our population. The overall prognosis was good.

PMID- 24462461
TI  - Improvement of cognitive function after carotid endarterectomy--a new strategy
      for the evaluation of cognitive function.
AB  - Significant carotid stenosis is known to cause ischemic stroke and cognitive
      impairment. However, it remains controversial whether carotid endarterectomy
      (CEA) can improve cognitive function in patients with carotid stenosis. We used
      the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE)
      to compare cognitive function between before and after CEA. Patients were
      prospectively registered to evaluate cognitive function from October 2011 to
      December 2012 after we determined them to have significant carotid stenosis.
      Patients were examined by 3-dimensional computed tomographic angiography or
      digital subtraction angiography. Although symptomatic cases were included, their
      modified Rankin Scale was grade 0 or 1 before CEA. All CEA procedures were
      performed by the same neurosurgical team. Cognitive function was evaluated by
      MoCA and MMSE performed before and after surgery. Data were analyzed
      statistically using the Wilcoxon signed rank test. Thirty-six patients were
      included in this study. The MoCA score after surgery, whereas the MMSE score was
      not. After surgery, the MoCA score improved in patients who were 73 years or
      younger, who underwent CEA in the left side of their carotid lesion, who had
      severe carotid stenosis of more than 80%, who had bilateral lesion, who did not
      have abnormal lesion on diffusion-weighted imaging after surgery, or who had
      cerebral blood flow of pre-CEA over 34.5 mL. In conclusion, MoCA was feasible in
      patients soon after undergoing CEA. Using MoCA not MMSE, CEA may improve
      cognitive function in patients with significant carotid stenosis. 

PMID- 24462462
TI  - HindIII polymorphism in the lipoprotein lipase gene and hypertensive
      intracerebral hemorrhage in the Chinese Han population.
AB  - BACKGROUND: To investigate the relationship between the HindIII polymorphism and
      hypertensive intracerebral hemorrhage (HIH) and lipid metabolism. METHODS: A
      polymerase chain reaction-restriction fragment length polymorphism assay and the
      chain termination DNA sequencing method were used to determine the HindIII
      genotypes of 267 subjects, which included 120 cerebral hemorrhagic patients and
      147 controls. The fasting levels of lipids and glucose in the plasma were used to
      measure the effect of genotype on HIH risk factors. RESULTS: The frequency of the
      T allele of the HindIII polymorphism in the HIH group was 90.8%. The frequency of
      the G allele was 9.2%. In the control group, the frequencies were 82.3% T and
      17.7% G, which indicated that the proportion of the G allele in the HIH patient
      group was significantly lower than in the control group (P<.05). The frequency of
      GG+GT genotypes in HIH patients (P<.05) and the plasma triglyceride (TG) levels
      in these patients (P<.05) were also lower than in the control group. The levels
      of plasma TG, low-density lipoprotein cholesterol, glucose, systolic blood
      pressure, and diastolic blood pressure in the HIH group were higher than in the
      controls (P<.05). After controlling for risk factors related to HIH, the HindIII
      G allele was negatively correlated with the incidence of HIH (odds ratio=.417,
      95% confidence interval: .193-.901). CONCLUSIONS: The HindIII G allele may be a
      protective factor against the development of HIH among the Han Chinese
      population.

PMID- 24462463
TI  - Clinical and prognostic implications of ALK and ROS1 rearrangements in never
      smokers with surgically resected lung adenocarcinoma.
AB  - OBJECTIVES: The aim of this study is to evaluate the prevalence and prognostic
      significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1)
      rearrangement in never-smokers with surgically resected lung adenocarcinoma.
      METHODS: We retrospectively analyzed 162 consecutive never-smokers who underwent
      curative resection for stage IB to IIIA lung adenocarcinoma at a single
      institution. We concurrently analyzed mutations in the epidermal growth factor
      receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)
      genes, and investigated ALK rearrangements by fluorescence in situ hybridization
      assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)
      negative tumors. RESULTS: Of 162 never smokers with lung adenocarcinoma, 14
      (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of
      the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK
      or ROS1 fusion). Fusion-positive patients tended to have shorter median disease
      free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months;
      p=0.128). In multivariate analysis, fusion-positive patients had significantly
      poorer DFS than fusion-negative patients after adjustment for age, sex, T stage,
      N stage, and adjuvant chemotherapy use (p=0.022; hazard ratio, 2.11; 95%
      confidence interval, 1.19-4.30). The first recurrence sites were not
      significantly different between fusion-positive and fusion-negative patients in
      this study. CONCLUSION: This study shows significantly poorer DFS of ALK or ROS1
      fusion-positive lung adenocarcinoma in never-smokers after curative surgery.

PMID- 24462464
TI  - Randomized, double-blind phase II study to compare nitroglycerin plus oral
      vinorelbine plus cisplatin with oral vinorelbine plus cisplatin alone in patients
      with stage IIIB/IV non-small cell lung cancer (NSCLC).
AB  - OBJECTIVES: Adding nitroglycerin to the combination of vinorelbine plus cisplatin
      has been reported to improve the overall survival (OS) of Asian patients with
      stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug
      delivery based on changed vascular tonus. The main objective of our study was to
      evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a
      Caucasian population. METHODS: 66 chemonaive patients with stage IIIB/IV NSCLC
      received oral vinorelbine (first cycle 60 mg/m(2), subsequent cycles: 80 mg/m(2)
      in the absence of any hematological toxicity >= grade 3 in cycle 1) once daily on
      days 1 and 8 of each cycle and cisplatin (80 mg/m(2) i.v.) on day 1 of each cycle
      (q3w). Nitroglycerin (arm A, n=34) or placebo patches (arm B, n=32) were
      administered once daily from day -3 to day 2 of each cycle and were removed about
      12h after administration. One nitroglycerin patch contained 25mg nitroglycerin.
      RESULTS: Median age was 62.5 (33-82) years. In the overall population (n=66), the
      objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0-39.6), with a
      disease control rate (DCR) of 57.6% (95%CI: 44.8-69.7), a median time to
      progression (TTP) of 4.8 months (n=58; 95%CI: 3.4-5.9) and a median overall
      survival (OS) of 11.5 months (95%CI: 7.9-13.6). ORR and DCR were numerically
      higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%,
      respectively), whereas TTP and OS were comparable. The main hematological and non
      hematological toxicities grade >= 3 were moderate with no significant differences
      between the two treatment arms. CONCLUSIONS: Overall, oral vinorelbine plus
      cisplatin showed a high level of efficacy and adequate tolerability in first line
      treatment of NSCLC. Despite the low sample size per group the results seem to
      confirm the previous results reported in Asian patients.

PMID- 24462465
TI  - Tunable aqueous polymer-phase impregnated resins-technology-a novel approach to
      aqueous two-phase extraction.
AB  - Aqueous Two-Phase Extraction (ATPE) represents a promising unit operation for
      downstream processing of biotechnological products. The technique provides
      several advantages such as a biocompatible environment for the extraction of
      sensitive and biologically active compounds. However, the tendency of some
      aqueous two-phase systems to form intensive and stable emulsions can lead to long
      phase separation times causing an increased footprint for the required mixer
      settler devices or the need for additional equipment such as centrifuges. In this
      work, a novel approach to improve ATPE for downstream processing applications
      called 'Tunable Aqueous Polymer-Phase Impregnated Resins' (TAPPIR((r)))
      Technology is presented. The technology is based on the immobilization of one
      aqueous phase inside the pores of a solid support. The second aqueous phase forms
      the bulk liquid around the impregnated solids. Due to the immobilization of one
      phase, phase emulsification and phase separation of ATPE are realized in a single
      step. In this study, a biodegradable and sustainable aqueous two-phase system
      consisting of aqueous polyethylene glycol/sodiumcitrate solutions was chosen. The
      impregnation of different macroporous glass and ceramic solids was investigated
      and could be proven to be stable. Additionally, the separation of the dye Patent
      blue V was successfully performed with the TAPPIR((r))-Technology. Thus, the
      "proof of principle" of this technology is presented. 

PMID- 24462466
TI  - Separation efficiency of dual-selector systems in capillary electrophoresis.
AB  - We introduce an easy but highly descriptive model of separation efficiency of
      dual-selector systems in capillary electrophoresis. The model expresses effective
      mobilities of analytes in dual-selector mixtures as a function of mixture
      composition and total concentration. The effective mobility follows the pattern
      familiar from single-selector systems, while complexation constant and mobility
      of the complex are replaced by the same but "overall" parameters and a total
      concentration of the mixture takes the role of a selector concentration. The
      overall parameters can be either calculated from the individual ones (an
      arbitrary mixture) or measured directly (a particular mixture). We inspected two
      model dual-selector systems consisting of heptakis(2,6-di-O-methyl)-beta-CD and
      beta-CD and of heptakis(2,6-di-O-methyl)-beta-CD and 6-O-alpha-maltosyl-beta-CD,
      and ibuprofen and flurbiprofen as model analytes (pH 8.2, non-enantioselective
      separation). Adopting any optimization strategy typically used in single-selector
      systems and finding an optimal mixture composition and total concentration is
      perhaps the prime benefit of the model. We demonstrate this approach on the
      selectivity parameter and show that the model is precise enough to be used in
      analytical practice. It also results that an electromigration order (reversal) of
      analytes can exhibit a rather curious dependency on the mixture composition and
      concentration. Last, the model can be used for better understanding of separation
      principles in dual-selector systems in general. 

PMID- 24462467
TI  - Orthogonal ion pairing reversed phase liquid chromatography purification of
      oligonucleotides with bulky fluorophores.
AB  - A dual labeled oligonucleotide used as TaqMan(r) or 5' nuclease probe for in
      vitro diagnostic has been purified through orthogonal ion-pairing reversed phase
      chromatography, using polymeric semi-preparative and preparative PRP-1 column. We
      studied the mechanism of separation of oligonucleotides using ion-pairing
      reversed phase chromatography. We found that elution profiles of dye labeled
      oligonucleotides can be controlled by use of specific ion-pairing reagents. Here,
      we report a method for purification of an oligonucleotide containing an
      internally positioned rhodamine dye using two orthogonal chromatographic steps,
      in which the primary step resolves mostly by differences in hydrophobicity by
      using a weak ion-pairing reagent, and a secondary step uses a strong ion-pairing
      reagent for separation of length variants. Purification is demonstrated for both
      1 and 15MUmol scale syntheses, and amenable to further scale up for commercial
      lot production. 

PMID- 24462468
TI  - RIF1: a novel regulatory factor for DNA replication and DNA damage response
      signaling.
AB  - DNA double strand breaks (DSBs) are highly toxic to the cells and accumulation of
      DSBs results in several detrimental effects in various cellular processes which
      can lead to neurological, immunological and developmental disorders. Failure of
      the repair of DSBs spurs mutagenesis and is a driver of tumorigenesis, thus
      underscoring the importance of the accurate repair of DSBs. Two major canonical
      DSB repair pathways are the non-homologous end joining (NHEJ) and homologous
      recombination (HR) pathways. 53BP1 and BRCA1 are the key mediator proteins which
      coordinate with other components of the DNA repair machinery in the NHEJ and HR
      pathways respectively, and their exclusive recruitment to DNA breaks/ends
      potentially decides the choice of repair by either NHEJ or HR. Recently, Rap1
      interacting factor 1 has been identified as an important component of the DNA
      repair pathway which acts downstream of the ATM/53BP1 to inhibit the 5'-3' end
      resection of broken DNA ends, in-turn facilitating NHEJ repair and inhibiting
      homology directed repair. Rif1 is conserved from yeast to humans but its function
      has evolved from telomere length regulation in yeast to the maintenance of genome
      integrity in mammalian cells. Recently its role in the maintenance of genomic
      integrity has been expanded to include the regulation of chromatin structure,
      replication timing and intra-S phase checkpoint. We present a summary of these
      important findings highlighting the various aspects of Rif1 functions and discuss
      the key implications for genomic integrity. 

PMID- 24462469
TI  - Neocartilage formation from mesenchymal stem cells grown in type II collagen
      hyaluronan composite scaffolds.
AB  - Three-dimensional (3D) collagen type II-hyaluronan (HA) composite scaffolds (CII
      HA) which mimics the extracellular environment of natural cartilage were
      fabricated in this study. Rheological measurements demonstrated that the
      incorporation of HA increased the compression modulus of the scaffolds. An
      initial in vitro evaluation showed that scaffolds seeded with porcine
      chondrocytes formed cartilaginous-like tissue after 8 weeks, and HA functioned to
      promote the growth of chondrocytes into scaffolds. Placenta-derived multipotent
      cells (PDMC) and gingival fibroblasts (GF) were seeded on tissue culture
      polystyrene (TCPS), CII-HA films, and small intestinal submucosa (SIS) sheets for
      comparing their chondrogenesis differentiation potentials with those of adipose
      derived adult stem cells (ADAS) and bone marrow-derived mesenchymal stem cells
      (BMSC). Among different cells, PDMC showed the greatest chondrogenic
      differentiation potential on both CII-HA films and SIS sheets upon TGF-beta3
      induction, followed by GF. This was evidenced by the up-regulation of
      chondrogenic genes (Sox9, aggrecan, and collagen type II), which was not observed
      for cells grown on TCPS. This finding suggested the essential role of substrate
      materials in the chondrogenic differentiation of PDMC and GF. Neocartilage
      formation was more obvious in both PDMC and GF cells plated on CII-HA composite
      scaffolds vs. 8-layer SIS at 28 days in vitro. Finally, implantation of PDMC/CII
      HA constructs into NOD-SCID mice confirmed the formation of tissue-engineered
      cartilage in vivo. 

PMID- 24462470
TI  - Patterns of viral load decline with telaprevir-based therapy in patients with
      genotype 1 chronic HCV infection.
AB  - BACKGROUND: Telaprevir-based therapy is associated with rapid decline in HCV RNA,
      enabling the application of early futility rules. OBJECTIVES: To familiarize
      physicians with this paradigm, a comprehensive analysis of the most frequent HCV
      viral load profiles observed during treatment with telaprevir/Peg-IFN/RBV in
      Phase III trials is provided. DESIGN: HCV RNA profiles were analyzed from 320 HCV
      genotype 1 treatment-naive patients enrolled in the ADVANCE study, and 225 prior
      Peg-IFN/RBV treatment-experienced patients enrolled in the REALIZE study.
      Patients received 12 weeks of telaprevir with either 24 or 48 weeks of Peg-IFN
      alfa-2a/RBV. Patients with missing SVR assessments during follow-up, detectable
      HCV RNA at end of treatment but who did not have viral breakthrough (vBT), or
      with early vBT who discontinued telaprevir before time of failure were excluded.
      RESULTS: All analyzed patients experienced a rapid decline in HCV RNA (>2.0
      log(10)) by Day 14, irrespective of baseline characteristics and/or prior
      response to Peg-IFN/RBV (relapse, partial response and null response).
      Subsequently, HCV RNA continued to decline to undetectable levels in most
      patients. These patients went on to have one of the following outcomes: sustained
      virologic response, late vBT (after Week 12, i.e. during the Peg-IFN/RBV phase),
      or relapse. In the small subset of patients with early vBT or meeting a futility
      rule before Week 12, HCV RNA usually never became undetectable and/or increased
      rapidly after reaching the nadir. CONCLUSIONS: HCV RNA profiles with
      telaprevir/Peg-IFN/RBV are different from those with Peg-IFN/RBV alone. It is
      important that clinicians understand these HCV RNA profiles and monitor patient
      viral load in order to apply futility rules correctly.

PMID- 24462471
TI  - In vitro detection of cytotoxicity using FluoroJade-C.
AB  - We describe here a novel method for the determination of cytotoxicity in cell
      cultures using Fluoro-Jade C (FJ-C). FJ-C has been previously used for the
      assessment of neurodegeneration in fixed brain tissue samples, and has never been
      utilized in live cell cultures or in different types of cells other than neurons.
      In the present study we examined the utility of FJ-C for the determination of
      cytotoxicity in vitro. Various cell cultures were evaluated including neural stem
      cells, brain microvessel endothelial cells, and SH-SY5Y, PC12 and MDCK cells.
      Cytotoxicities induced by toxicants in cell cultures, as determined by the FJ-C
      labeling, were further confirmed by commonly used cytotoxicity assays. This in
      vitro approach is simple, fast, and sensitive and, thus, has the potential to
      augment if not replace currently used cell-based cytotoxicity assays. 

PMID- 24462472
TI  - Recovery and well-being among Helicopter Emergency Medical Service (HEMS) pilots.
AB  - This study investigated the effects of a compressed working week with high
      cognitive and emotional work demands within the population of Dutch Helicopter
      Emergency Medical Service (HEMS) pilots. Work stressors were measured and levels
      of well-being were examined before, during and after a series of day and night
      shifts. Results revealed that (i) the start of a series of day shifts was more
      taxing for well-being than the start of a series of night shifts, (ii) there were
      no differences in the decrease in well-being during day and night shifts, (iii)
      distress during shifts was more strongly related to a decrease in well-being
      during night than during day shifts and (iv) it took HEMS pilots more time to
      recover from a series of night shifts than from a series of day shifts. It is
      concluded that HEMS pilots should not start earlier during day shifts, nor have
      longer series of night shifts. 

PMID- 24462473
TI  - Measured and perceived environmental comfort: field monitoring in an Italian
      school.
AB  - Microclimatic conditions were recorded in an Italian school and Fanger's indexes
      PMV and PPD were calculated under different conditions. Students' sensations were
      investigated four times by means of two surveys, one related to actual
      microclimatic conditions and one on overall satisfaction, interaction occupant
      building and reactions to discomfort. Pupils' classroom position was considered
      to look for possible influence on thermal comfort: a difference emerged from PMV
      and the survey, but the results obtained from the two approaches differ for both
      the entity of discomfort and its distribution within each classroom. Innovative
      multivariate nonparametric statistical techniques were applied to compare and
      rank the classrooms in accordance with students' subjective perceptions; a global
      ranking has been also calculated, considering thermal and visual comfort and air
      quality. Comparing pupil-sensation-based ranking with environmental parameters no
      clear correspondence was found, except for mid-season, where PMV, CO2
      concentration and desk illuminance were similar in all the classrooms. 

PMID- 24462474
TI  - Comparison of firefighters and non-firefighters and the test methods used
      regarding the effects of personal protective equipment on individual mobility.
AB  - The aims of this study were 1) to evaluate the current pilot test method and
      ascertain reliable measurements for a standard test method of mobility with
      personal protective equipment (PPE), such as physical performance and balance
      ability tests; 2) to compare two participant groups (firefighters versus non
      firefighters) and to investigate whether non-firefighters are appropriate as a
      standard participant group in the field of PPE or not. Totally, 18 participants
      (nine professional firefighters and nine untrained males) performed the current
      pilot test method consisting of a balance test, completed prior to and after a
      performance test. Significant differences were found between PPE conditions and
      CON (the control clothing ensemble: T-shirt, shorts, and running shoes) for the
      functional balance test, physical performance test, heart rate, and subjective
      evaluations in firefighters group. Therefore, the present pilot test method is
      valid as a standard test method for assessing mobility while wearing PPE.
      Moreover, the present result shows that firefighters are more reliable than non
      firefighters in testing of PPE with current test methods. 

PMID- 24462475
TI  - The role of CD81 for plasma cell dyscrasias.

PMID- 24462476
TI  - Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a
      systematic review.
AB  - BACKGROUND: To evaluate the safety and efficacy of using sildenafil for >= 12
      weeks to treat pulmonary arterial hypertension (PAH). METHODS: Randomized
      controlled trials (RCTs) of sildenafil therapy in patients with PAH published
      through May 2013 were identified by searching PubMed, the Cochrane Library,
      Embase, relevant websites, and reference lists of relevant studies. Two reviewers
      independently assessed the quality of the trials and extracted information.
      RESULTS: Meta-analysis was carried out with subsets of 4 trials involving 545
      patients. Sildenafil therapy significantly reduced clinical worsening of PAH
      compared to placebo (RR 0.39, 95% CI 0.21-0.69) and improved the 6-min walk
      distance (MD 31.3 m, 95% CI 18.01-44.67), WHO functional class, hemodynamic
      variables and health-related quality of life (HRQoL). Sildenafil did not,
      however, improve all-cause mortality (RR 0.29, 95% CI 0.02-4.94) or Borg dyspnea
      score relative to placebo, nor did it significantly affect the incidence of
      serious adverse events. In fact, sildenafil was associated with higher total
      incidence of adverse events, but these additional events were mild to moderate in
      severity and were tolerable. CONCLUSIONS: Sildenafil therapy lasting >= 12 weeks
      improves multiple clinical and hemodynamic outcomes in patients with PAH, but it
      appears to have no effect on mortality or serious adverse events. The long-term
      efficacy and safety of sildenafil therapy in PAH requires further study based on
      large and well-designed RCTs.

PMID- 24462477
TI  - Lung cancer risk among patients with combined pulmonary fibrosis and emphysema.
AB  - Although combined pulmonary fibrosis and emphysema (CPFE) might be relevant to
      lung cancer, no comparison studies have been done. We evaluated the risk of lung
      cancer among CPFE patients compared to IPF and emphysema patients. We
      retrospectively reviewed the medical records of patients who were diagnosed as
      CPFE, IPF and emphysema using chest CT scans at Seoul National University
      Hospital from Jan 2000 to Dec 2011. Patients with CPFE were enrolled and matched
      (1:1:2) with IPF and emphysema patients based on the radiological criteria. The
      main outcome was time to diagnosis of lung cancer and evaluated with Cox
      proportional hazard regression. Forty-eight CPFE, 48 IPF, and 96 emphysema
      patients were included in this study. Twenty-five cases of lung cancer occurred.
      The CPFE group had a higher risk of lung cancer (adjusted HR 4.62, 95% CI 1.58
      13.55) than that of the emphysema group. Also, IPF group had a higher risk of
      lung cancer (adjusted HR 4.15, 95% CI 1.03-16.78) than that of emphysema group.
      However, there was no statistically significant difference in lung cancer risk
      between the CPFE and IPF group. Additionally, the CPFE group had a higher risk of
      lung cancer or death (adjusted HR 4.62, 95% CI 2.25-9.47) than that of the
      emphysema group. In conclusion, patients with CPFE and IPF had a higher risk of
      lung cancer than those with emphysema, although lung cancer risk was similar
      between CPFE and IPF. 

PMID- 24462478
TI  - A comparison of treatment outcomes for adolescent community reinforcement
      approach participants with and without co-occurring problems.
AB  - This study examined the relationship between Adolescent Community Reinforcement
      Approach (A-CRA) participation with treatment engagement, retention, and
      satisfaction, and with substance use and emotional problem outcomes. Participants
      had substance use disorders (SUD) only or co-occurring substance use and
      psychiatric problems. Those with co-occurring problems reported more days of
      substance use and emotional problems at intake to treatment than those with SUD
      only. All groups received equivalent exposure to A-CRA during treatment
      implementation. At the 12-month follow-up, adolescents classified as
      externalizers (n = 468) or those with both externalizing and internalizing
      problems (n = 674) had significantly greater improvement in their days of
      abstinence and substance problems relative to adolescents with substance use
      disorders only (n = 666). Additionally, adolescents reporting symptoms of
      internalizing (n = 154), externalizing, or both externalizing and internalizing
      disorders had significantly greater improvements in days of emotional problems
      relative to adolescents with SUD only.

PMID- 24462480
TI  - Differential effects of baseline drinking status: effects of an alcohol
      prevention program targeting students and/or parents (PAS) among weekly drinking
      students.
AB  - The effects of an intervention designed to prevent onset of weekly drinking in
      non drinking students (PAS) were investigated in the group of students that was
      already drinking at baseline. A cluster randomized trial was used including 3,490
      Dutch early adolescents (M age = 12.66, SD = 0.49) randomized over four
      conditions; 1) parent intervention, 2) student intervention, 3) combined
      intervention and 4) control group. Outcome measures were amount and growth of
      weekly alcohol drinking measured 10, 22 and 34 months after baseline. The
      combined intervention significantly curbed the growth of drinking among both non
      drinkers (the target group of the intervention) and drinkers at baseline.
      Overall, less strong increases of drinking over time are found among non-drinkers
      compared to drinkers at baseline. Thus, the combined PAS intervention is also
      effective in curbing adolescents' drinking behaviour in those who already were
      drinking at baseline. Broad implementation of the combined parent-student
      intervention is recommended.

PMID- 24462479
TI  - 12-step facilitation for the dually diagnosed: a randomized clinical trial.
AB  - There are few clinical trials of 12-step treatments for individuals with serious
      mental illness and alcohol or drug dependence. This randomized trial assessed the
      effects of adding a 12-session 12-step facilitation therapy (TSF), adapted from
      that used in Project MATCH, to treatment as usual in an outpatient dual diagnosis
      program. Participants were 121 individuals dually diagnosed with alcohol
      dependence and a serious mental disorder, followed during 12 weeks of treatment
      and 36 weeks post-treatment. Participants receiving TSF had greater participation
      in 12-step programs, but did not demonstrate greater improvement in alcohol and
      drug use. However, considered dimensionally, greater participation in TSF was
      associated with greater improvement in substance use, and greater 12-step
      participation predicted decreases in frequency and intensity of drinking.
      Findings suggest that future work with TSF in this population should focus on
      maximizing exposure to TSF, and maximizing the effect of TSF on 12-step
      participation. 

PMID- 24462481
TI  - Vaccination with a HSV-2 UL24 mutant induces a protective immune response in
      murine and guinea pig vaginal infection models.
AB  - The rational design and development of genetically attenuated HSV-2 mutant
      viruses represent an attractive approach for developing both prophylactic and
      therapeutic vaccines for genital herpes. Previously, HSV-2 UL24 was shown to be a
      virulence determinant in both murine and guinea pig vaginal infection models. An
      UL24-betagluc insertion mutant produced syncytial plaques and replicated to
      nearly wild type levels in tissue culture, but induced little or no pathological
      effects in recipient mice or guinea pigs following vaginal infection. Here we
      report that immunization of mice or guinea pigs with high or low doses of UL24
      betagluc elicited a highly protective immune response. UL24-betagluc immunization
      via the vaginal or intramuscular routes was demonstrated to protect mice from a
      lethal vaginal challenge with wild type HSV-2. Moreover, antigen re-stimulated
      splenic lymphocytes harvested from immunized mice exhibited both HSV-2 specific
      CTL activity and IFN-gamma expression. Humoral anti-HSV-2 responses in serum were
      Th1-polarized (IgG2a>IgG1) and contained high-titer anti-HSV-2 neutralizing
      activity. Guinea pigs vaccinated subcutaneously with UL24-betagluc or the more
      virulent parental strain (186) were challenged with a heterologous HSV-2 strain
      (MS). Acute disease scores were nearly indistinguishable in guinea pigs immunized
      with either virus. Recurrent disease scores were reduced in UL24-betagluc
      immunized animals but not to the same extent as those immunized with strain 186.
      In addition, challenge virus was not detected in 75% of guinea pigs
      subcutaneously immunized with UL24-betagluc. In conclusion, disruption of the
      UL24 gene is a prime target for the development of a genetically attenuated live
      HSV-2 vaccine.

PMID- 24462482
TI  - Efficacy of a recombinant Rift Valley fever virus MP-12 with NSm deletion as a
      vaccine candidate in sheep.
AB  - Rift Valley fever virus (RVFV), a mosquito-borne virus in the Bunyaviridae family
      and Phlebovirus genus, causes RVF, a disease of ruminants and man, endemic in Sub
      Saharan African countries. However, outbreaks in Yemen and Saudi Arabia
      demonstrate the ability for RVFV to spread into virgin territory and thus the
      need exists to develop safe and efficacious vaccines that can be used outside the
      endemic zones. Commercial RVFV vaccines are available but have limitations that
      prevent their use in disease-free countries. Consequently, there are ongoing
      efforts to develop and/or improve RVFV vaccines with global acceptability. In
      this study a previously developed MP-12-derived vaccine candidate with a large
      deletion of the NSm gene in the pre Gn region of the M segment (arMP-12
      DeltaNSm21/384) developed by T. Ikegami, that was already shown to be safe in
      pregnant sheep causing neither abortion nor fetal malformation was further
      evaluated. This vaccine was tested for protection of sheep from viremia and fever
      following challenge with virulent RVFV ZH501 strain. A single vaccination with
      arMP-12-DeltaNSm21/384 fully protected sheep when challenged four weeks post
      vaccination, thereby demonstrating that this vaccine is efficacious in protecting
      these animals from RVFV infection. 

PMID- 24462484
TI  - Self-reported physiological and psychological side-effects of an acute alcohol
      and energy drink dose.
AB  - OBJECTIVE: There have been repeated calls from health professionals and policy
      makers to clarify the side-effects of the increasingly popular consumption trend
      of alcohol mixed with energy drinks (AmED). There is a dearth of research
      assessing the differential effects of AmED relative to alcohol by comparing self
      reported psychological and physiological outcomes whilst under the influence of
      these substances. The aim of the present study was to examine the acute effects
      of a moderate alcohol and energy drink (ED) dose on self-reported psychological
      and physiological outcomes. METHOD: Using a single-blind, placebo-controlled,
      crossover design, 28 adults completed four sessions where they were administered:
      (i) 0.50g/kg alcohol, (ii) 3.57mL/kg ED, (iii) AmED, and (iv) placebo.
      Participants independently completed the Profile of Mood States and a Somatic
      Symptom Scale at baseline and at 30 and 125min after beverage administration.
      RESULTS: Breath alcohol concentration peaked at .068% and .067% in the alcohol
      and AmED conditions, respectively. There were no interactive alcohol and ED
      effects on self-reported psychological outcomes. Treatment effects for
      physiological outcomes generally only related to alcohol or ED administration,
      with the exception of a moderate magnitude decrease in heart palpitation ratings
      following alcohol relative to AmED. Decreased muscular tension ratings were
      evident when the two constituents were consumed separately relative to placebo.
      CONCLUSIONS: The results provide evidence of few subjective changes in
      physiological and psychological state after consuming AmED relative to alcohol.
      The majority of treatment-based changes arose from the independent effects of
      alcohol or ED, rather than being modified by their interaction. However, research
      extending into higher dosage domains is required to increase outcome
      generalisability for consumers in the night-time economy.

PMID- 24462485
TI  - Height, weight, and entry earnings of female graduates in Taiwan.
AB  - Using a data set of Taiwanese female graduates in 2006, this study finds that
      height and earnings are positively correlated for full-time workers. However, it
      is not because tall individuals went to better colleges or received better grades
      (cognitive ability), not because they are gifted with superior physical strength
      or because they have participated in more extracurricular activities (non
      cognitive ability), and not because they work in a highly paid occupation. We
      find that statistical discrimination (or perceptual bias) is most likely to play
      a role in determining the entry earnings of female graduates. In addition, we
      find that an estimator of the height premium for females is downward-biased if
      weight is omitted from the model. 

PMID- 24462483
TI  - Zinc or albendazole attenuates the progression of environmental enteropathy: a
      randomized controlled trial.
AB  - BACKGROUND & AIMS: Environmental enteropathy (EE) is a subclinical condition
      among children in the developing world, characterized by T-cell infiltration of
      the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and
      micronutrient malabsorption and stunting, with a resultant increased risk for
      infection and reduced cognitive development. We tested the hypothesis that zinc
      and albendazole treatments would reduce the severity of EE in rural African
      children. METHODS: In a randomized, double-blind, placebo-controlled trial in
      rural southern Malawi, asymptomatic children, 1 to 3 years old and at high risk
      for EE, received either a single dose of albendazole, a 14-day course of 20 mg
      zinc sulfate, or a placebo. Subjects were given the dual-sugar absorption test,
      and the ratio of lactulose to mannitol (L:M) in urine was used to determine the
      severity of EE at baseline and 34 days after completion of the assigned regimen.
      The primary outcome was the change in the L:M. RESULTS: A complete set of urine
      samples was obtained from 222 of 234 children enrolled and analyzed. The mean
      baseline L:M was 0.32 +/- 0.18 among all children and did not differ among groups
      (normal L:M range, <0.12). At the end of the study, the L:M ratio had increased
      more in the placebo group (0.12 +/- 0.31) than in the zinc group (0.03 +/- 0.20;
      P < .03) or the albendazole group (0.04 +/- 0.22; P < .04). CONCLUSIONS:
      Treatment with zinc or albendazole protects against a significant increase in the
      L:M ratio, a biomarker for EE, in asymptomatic rural Malawian children. These
      findings could provide insight into the etiology and pathogenesis of EE.
      Clinicaltrials.gov Number: NCT01440608.

PMID- 24462486
TI  - Family mealtimes and eating psychopathology: the role of anxiety and depression
      among adolescent girls and boys.
AB  - Characteristics of family mealtimes are associated with disordered eating
      behaviours. However, little is known about the relationships between
      characteristics of family mealtimes and disordered eating attitudes, or how
      symptoms of anxiety or depression may contribute to these relationships. This
      study therefore aimed to examine differences between adolescent girls and boys in
      the relationship between family mealtime characteristics and eating
      psychopathology, and to explore the influence of anxiety and depression on this
      relationship. Adolescents (N=535; 286 girls and 249 boys) aged 14-18years
      completed self-report measures of family mealtime characteristics, eating
      psychopathology, anxiety and depression. Reports of more frequent family
      mealtimes, a more positive mealtime atmosphere and a high level of priority
      placed on mealtimes were all associated with significantly lower levels of eating
      disordered attitudes among girls only. For boys, all four mealtime measures
      (higher mealtime frequency, more positive mealtime atmosphere, greater priority
      of mealtimes and higher levels of mealtime structure) were associated with lower
      levels of depression. Among girls, several of the family mealtime and eating
      psychopathology relationships were partially or fully mediated by either anxiety
      or depression. While these findings require longitudinal replication, family
      mealtimes are likely to be important in promoting psychological well-being among
      both girls and boys. Families should be encouraged to think beyond the frequency
      of mealtimes and to foster a positive mealtime environment which may help to
      promote adolescent psychological wellbeing, and might even protect young females
      against the development of eating psychopathology. 

PMID- 24462488
TI  - Colour, pleasantness, and consumption behaviour within a meal.
AB  - It is often claimed that colour (e.g., in a meal) affects consumption behaviour.
      However, just how strong is the evidence in support of this claim, and what are
      the underlying mechanisms? It has been shown that not only the colour itself, but
      also the variety and the arrangement of the differently-coloured components in a
      meal influence consumers' ratings of the pleasantness of a meal (across time)
      and, to a certain extent, might even affect their consumption behaviour as well.
      Typically, eating the same food constantly or repeatedly leads to a decrease in
      its perceived pleasantness, which, as a consequence, might lead to decreased
      intake of that food. However, variation within a meal (in one or several sensory
      attributes, or holistically) has been shown to slow down this process. In this
      review, we first briefly summarize the literature on how general variety in a
      meal influences these variables and the major theories that have been put forward
      by researchers to explain them. We then go on to evaluate the evidence of these
      effects based mainly on the colour of the food explaining the different processes
      that might affect colour-based sensory-specific satiety and, in more detail,
      consumption behaviour. In addition, we also discuss the overlap in the
      definitions of these terms and provide additional hypothesis as to why, in some
      cases, the opposite pattern of results has been observed. 

PMID- 24462489
TI  - Watching television while eating increases energy intake. Examining the
      mechanisms in female participants.
AB  - Watching television (TV) while eating tends to increase food intake, but why this
      occurs is not well understood. Here, we examined TV's effects on sensory specific
      satiety (SSS), introception (i.e., hunger/fullness), mood and other variables, in
      females who all ate one snack meal with TV and another without TV. To manipulate
      the development of SSS, participants were assigned either to a group receiving a
      single type of snack food or one receiving four types. Everyone ate more with TV.
      More food items were eaten in the group offered multiple snack types. In the
      group eating a single snack type with TV, hedonic ratings indicated that SSS did
      not develop and this was associated with greater food intake. Irrespective of
      group, more food had to be consumed to generate the same shift in hunger/fullness
      when eating with TV, relative to no TV. TV exerted less effect on food intake
      both if it improved mood and if participants were unfamiliar with the TV show,
      and a greater effect if participants were frequent TV viewers. We suggest that TV
      can affect several processes that normally assist the voluntary regulation of
      food intake. 

PMID- 24462487
TI  - Associations of ghrelin with eating behaviors, stress, metabolic factors, and
      telomere length among overweight and obese women: preliminary evidence of
      attenuated ghrelin effects in obesity?
AB  - Ghrelin regulates homeostatic food intake, hedonic eating, and is a mediator in
      the stress response. In addition, ghrelin has metabolic, cardiovascular, and anti
      aging effects. This cross-sectional study examined associations between total
      plasma ghrelin, caloric intake based on 3day diet diaries, hedonic eating
      attitudes, stress-related and metabolic factors, and leukocyte telomere length in
      overweight (n=25) and obese women (n=22). We hypothesized associations between
      total plasma ghrelin and eating behaviors, stress, metabolic, cardiovascular, and
      cell aging factors among overweight women, but not among obese women due to lower
      circulating ghrelin levels and/or central resistance to ghrelin. Confirming
      previous studies demonstrating lowered plasma ghrelin in obesity, ghrelin levels
      were lower in the obese compared with overweight women. Among the overweight,
      ghrelin was positively correlated with caloric intake, giving in to cravings for
      highly palatable foods, and a flatter diurnal cortisol slope across 3days. These
      relationships were non-significant among the obese group. Among overweight women,
      ghrelin was negatively correlated with insulin resistance, systolic blood
      pressure, and heart rate, and positively correlated with telomere length. Among
      the obese subjects, plasma ghrelin concentrations were negatively correlated with
      insulin resistance, but were not significantly correlated with blood pressure,
      heart rate or telomere length. Total plasma ghrelin and its associations with
      food intake, hedonic eating, and stress are decreased in obesity, providing
      evidence consistent with the theory that central resistance to ghrelin develops
      in obesity and ghrelin's function in appetite regulation may have evolved to
      prevent starvation in food scarcity rather than cope with modern food excess.
      Furthermore, ghrelin is associated with metabolic and cardiovascular health, and
      may have anti-aging effects, but these effects may be attenuated in obesity. 

PMID- 24462490
TI  - Defining food literacy and its components.
AB  - Food literacy has emerged as a term to describe the everyday practicalities
      associated with healthy eating. The term is increasingly used in policy,
      practice, research and by the public; however, there is no shared understanding
      of its meaning. The purpose of this research was to develop a definition of food
      literacy which was informed by the identification of its components. This was
      considered from two perspectives: that of food experts which aimed to reflect the
      intention of existing policy and investment, and that of individuals, who could
      be considered experts in the everyday practicalities of food provisioning and
      consumption. Given that food literacy is likely to be highly contextual, this
      second study focused on disadvantaged young people living in an urban area who
      were responsible for feeding themselves. The Expert Study used a Delphi
      methodology (round one n=43). The Young People's Study used semi-structured, life
      course interviews (n=37). Constructivist Grounded Theory was used to analyse
      results. This included constant comparison of data within and between studies.
      From this, eleven components of food literacy were identified which fell into the
      domains of: planning and management; selection; preparation; and eating. These
      were used to develop a definition for the term "food literacy". 

PMID- 24462491
TI  - Food preparation supplies predict children's family meal and home-prepared dinner
      consumption in low-income households.
AB  - Frequent family meals and home food preparation are considered important for
      children's nutritional health and weight maintenance. This cross-sectional study
      tested whether these parent-driven behaviors are related to the availability of
      food preparation supplies in low-income urban households. Caregivers of children
      ages 6-13 provided information on family meal frequency, child consumption of
      home-prepared dinners, household food insecurity, and attitudes towards cooking.
      Researchers used a newly developed Food Preparation Checklist (FPC) to assess the
      availability of 41 food preparation supplies during a physical audit of the home
      environment. Caregivers and children provided anthropometric measurements and
      jointly reported on child dietary intake. In ordinal logistic regression models,
      greater home availability of food preparation supplies was associated with more
      frequent family meals and child consumption of home-prepared dinners.
      Associations were independent of household financial strain, food insecurity,
      caregiver attitudes toward cooking, and sociodemographic characteristics. Fewer
      food preparation supplies were available in households characterized by greater
      food insecurity, lower income, and negative caregiver attitudes towards cooking,
      but did not differ by child or caregiver weight status. As in prior studies, more
      frequent family meals and consumption of home-prepared dinners were associated
      with healthier child dietary intake in several areas. We conclude that food
      preparation supplies are often limited in the most socioeconomically
      disadvantaged households, and their availability is related to the frequency with
      which children consume family meals and home-prepared dinners. The potential role
      of food preparation supplies as contributors to socioeconomic disparities in
      child nutritional health and obesity deserves further study. 

PMID- 24462492
TI  - Impact of a non-attentively perceived odour on subsequent food choices.
AB  - Current research in psychology suggests that unconscious processes influence a
      significant proportion of choices and decisions. To study the impact of a non
      attentively perceived odour on food choices, we used a priming paradigm. We had
      previously shown that non-attentively perceived fruity odours could impact food
      choice intentions (on a menu card), guiding participants toward items containing
      more fruit and/or vegetables. The present study was designed to extend these
      findings, in a real-life consumption setting. One hundred and fifteen
      participants took part in this study, and were assigned randomly to either a
      control or a scented condition. On arrival in the laboratory, they were seated in
      a waiting room. For the scented condition, they were unobtrusively exposed to a
      pear odour, while under the control condition the waiting room was non-odorised.
      Following this waiting period, all participants moved into a non-odorised test
      room where they were asked to choose, from dishes served buffet-style, the
      starter, main course and dessert that they would actually eat for lunch. The
      results showed that participants subjected to the scented condition chose to
      consume the 'fruity' dessert (compote) more frequently than those who had waited
      under the control condition, who chose more frequently the dessert without fruit
      (brownie). In line with the findings of our previous study, these results confirm
      the idea of priming effects 'specific to the food cue'. To conclude, a non
      attentively perceived fruity odour was shown to influence actual food choices,
      guiding individuals towards more fruity desserts. The involvement of implicit
      processes in food choices should be taken into account in guidelines and
      strategies designed to promote healthy eating. 

PMID- 24462493
TI  - A qualitative exploration of experiences of overweight young and older adults. An
      application of the integrated behaviour model.
AB  - While rates of obesity continue to increase, weight-loss interventions to date
      have not been hugely successful. The purpose of this study was to explore the
      specific factors that are relevant to weight control in overweight and obese
      young adults compared to older adults, within the context of the theory of
      planned behaviour (TPB). A qualitative methodology with purposive sampling was
      used. Semi-structured interviews were conducted with 23 young adults and older
      adults who were currently overweight or obese. The research was informed by
      thematic analysis. A mixed deductive-inductive approach that was structured
      around but not limited to TPB constructs was applied. Themes mapped onto the TPB
      behaviour well, with additional themes of motivation, and knowledge and
      experience emerging. Differences across groups included motivators to weight loss
      (e.g. appearance and confidence for young adults, health for older adults),
      importance of social influences, and perceptions of control (e.g. availability
      and cost for young adults, age and energy for older adults). Similarities across
      groups included attitudes towards being overweight and losing weight, and the
      value of preparation and establishment of a healthy routine. Finally, across both
      groups, knowledge and confidence in ability to lose weight appeared adequate,
      despite failed attempts to do so. The different experiences identified for
      younger and older adults can be used to inform future tailored weight-loss
      interventions that are relevant to these age groups, and the TPB could provide a
      useful framework. Additional intervention strategies, such as improving
      behavioural routine and improving self-regulation also warrant further
      investigation. 

PMID- 24462495
TI  - T-cell inhibitory capacity of hyperimmunoglobulins is influenced by the
      production process.
AB  - Intravenous immunoglobulin (IVIg) preparations are widely used for anti
      inflammatory therapy of autoimmune and systemic inflammatory diseases.
      Hyperimmunoglobulins enriched in neutralizing antibodies against viruses can, in
      addition to their virus-neutralizing activity, also exert immunomodulatory
      activity. Previously, we observed that Cytotect(r), an anti-CMV
      hyperimmunoglobulin, was less effective in suppressing human T-cell responses in
      vitro compared to Hepatect(r) CP, an anti-HBV hyperimmunoglobulin. We
      hypothesized that the poor immunomodulatory activity of Cytotect(r) results from
      treatment with beta-propiolactone during the manufacturing process. The
      manufacturer of these hyperimmunoglobulins has now introduced a new anti-CMV
      hyperimmunoglobulin, called Cytotect(r) CP, in which beta-propiolactone treatment
      is omitted. Here we show that Cytotect(r) CP inhibits PHA-driven T-cell
      proliferation and cytokine production with similar efficacy as Hepatect(r) CP,
      whereas the former Cytotect(r) does not. In addition, Cytotect(r) CP inhibits
      allogeneic T-cell responses better than Cytotect(r). Our results advocate the use
      of hyperimmunoglobulins that have not been exposed to beta-propiolactone in order
      to benefit from their immunomodulatory properties. 

PMID- 24462494
TI  - Tangeretin exerts anti-neuroinflammatory effects via NF-kappaB modulation in
      lipopolysaccharide-stimulated microglial cells.
AB  - Increasing evidence suggests that tangeretin, a flavonoid from citrus fruit
      peels, exhibits anti-inflammatory properties and neuroprotective effects in
      animal disease models. However, the underlying molecular mechanisms are not
      clearly understood. In this study, we investigated whether tangeretin suppresses
      excessive microglial activation implicated in the resulting neurotoxicity
      following stimulation with lipopolysaccharide (LPS) in primary rat microglia and
      BV-2 microglial cell culture models. The results showed that tangeretin decreased
      the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis
      factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL
      6), in a dose-dependent manner. Additionally, it inhibited the LPS-induced
      expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined
      at the protein level) as well as TNF-alpha, IL-1beta, and IL-6 (examined at the
      mRNA level) in microglial cells. To explore the possible mechanisms underlying
      these inhibitions by tangeretin, we examined the mitogen-activated protein kinase
      (MAPK) protein levels and the NF-kappaB protein signaling pathway. Tangeretin
      clearly inhibited LPS-induced phosphorylation of ERK, N-terminal Kinase (JNK),
      and p38. In addition, tangeretin markedly reduced LPS-stimulated phosphorylation
      of IkappaB-alpha and IKK-beta, as well as the nuclear translocation of the p65
      subunit of pro-inflammatory transcription factor NF-kappaB. Taken together, these
      results support further exploration of the therapeutic potential and molecular
      mechanism of tangeretin in relation to neuroinflammation and neurodegenerative
      diseases accompanied by microglial activation.

PMID- 24462496
TI  - Reasons for phosphate binder discontinuation vary by binder type.
AB  - OBJECTIVE: Nonadherence to phosphate binder regimen is common among end-stage
      renal disease patients and contributes to elevated phosphorus levels. Pill
      burden, side effects, complex regimens, and cost all contribute to nonadherence.
      We retrospectively analyzed reasons for discontinuation in hemodialysis patients
      receiving treatment at a large U.S. dialysis organization to better understand
      the drivers of nonadherence for particular phosphate binders. DESIGN AND SETTING:
      Patient electronic medical records were reviewed to identify phosphate binder
      prescriptions and reasons for discontinuation. Reasons for discontinuation were
      categorized and the percentage of patients on each type of phosphate binder was
      calculated within categories. SUBJECTS: Medicare patients of age >=18 years,
      receiving in-center hemodialysis treatment between July 1, 2009, and June 30,
      2011, were included in the analysis. RESULTS: We classified 30,933 patient
      records with a stated reason for phosphate binder discontinuation for this study.
      Of these records, 50.1% cited that the patient discontinued the phosphate binder
      but contained no additional information; "lab results" were cited for 27.4% of
      the reasons for discontinuation and "patient-reported side effects" for 10.8%.
      Although patients on lanthanum carbonate accounted for 14% of the total number
      reasons for discontinuation assessed, they comprised 40% of the "patient-reported
      side effects" category and were similarly overrepresented in 4 of the 5
      subcategories. CONCLUSIONS: The high percentage of patient-reported side effects
      resulting in discontinuation identifies an unmet need for improved phosphate
      binders. A disproportionate percentage of patients prescribed lanthanum carbonate
      reported side effects, however further work is needed to identify the relative
      tolerability of phosphate binders and potential explanations.

PMID- 24462497
TI  - Acyl-ghrelin and obestatin plasma levels in different stages of chronic kidney
      disease.
AB  - OBJECTIVE: This study assessed acyl-ghrelin and obestatin plasma levels in
      nondialysis chronic kidney disease (CKD) and hemodialysis (HD) patients compared
      with healthy volunteers. DESIGN: This was a cross-sectional study conducted at
      Renal Vida Clinic (Rio de Janeiro, Brazil) and Renal Nutrition Ambulatory
      (Niteroi, Brazil). SUBJECTS: Sixty-four subjects were studied: 29 HD patients
      (55.4 +/- 10.5 years, body mass index [BMI], 24.4 +/- 3.9 kg/m(2), 17 men); 19
      nondialysis patients (59.8 +/- 7.5 years, BMI, 26.3 +/- 4.8 kg/m(2), glomerular
      filtration rate, 28.8 +/- 10.5 mL/minute/1.73 m(2), 5 men), and 16 healthy
      volunteers (53.8 +/- 5.4 years, BMI, 24.6 +/- 2.7 kg/m(2), 7 men). MAIN OUTCOME
      MEASURE: Acyl-ghrelin and obestatin were assessed using enzyme immunometric
      assays. Body weight, height, waist circumference (WC), and skinfold were
      measurement, and body fat percentage, arm muscle area, BMI, and conicity index
      were calculated. The average daily intake of calories and protein were estimated
      using a 3-day, 24-hour dietary recall, and the appetite was assessed by the first
      question of the Hemodialysis Study Appetite Questionnaire. RESULTS: The highest
      serum acyl-ghrelin (34.1 +/- 13.0 pg/mL) and acyl-ghrelin/obestatin ratio (34.0
      [6.7-90.2]) were found in nondialysis CKD patients who also presented with the
      lowest obestatin levels (0.8 [0.30-2.7] ng/mL) when compared with HD patients and
      healthy volunteers. HD patients presented the highest obestatin plasma levels
      (3.0 [2.7-3.4] ng/mL) and the lowest acyl-ghrelin/obestatin ratio (P < .05).
      Obestatin levels inversely correlated with WC (r = -0.6, P < .04) and BMI (r = 
      0.56, P < .04) in healthy volunteers. CONCLUSION: Although no correlation was
      found for appetite and food intake with acyl-ghrelin and obestatin in CKD
      patients, HD patients have the most important alteration of acyl-ghrelin and
      obestatin plasma levels and had a more impaired nutritional status than
      nondialysis CKD individuals.

PMID- 24462498
TI  - Adherence to hemodialysis dietary sodium recommendations: influence of patient
      characteristics, self-efficacy, and perceived barriers.
AB  - OBJECTIVE: To identify characteristics of hemodialysis patients most likely to
      experience difficulty adhering to sodium restrictions associated with their
      dietary regimen. DESIGN: Secondary analysis using baseline data from an ongoing
      randomized clinical trial examining the effects of a technology-supported
      behavioral intervention on dietary sodium intake in hemodialysis patients.
      SETTING: Thirteen dialysis centers in southwestern Pennsylvania. SUBJECTS: We
      included 122 participants (61% women; 48% African American) aged 61 +/- 14 years
      undergoing maintenance, intermittent hemodialysis for end-stage renal disease.
      MAIN OUTCOME MEASURES: Normalized dietary sodium intake, adjusted interdialytic
      weight gain, perceived problems, and self-efficacy for restricting dietary
      sodium. RESULTS: Younger participants were more likely to report problems
      managing their hemodialysis diet and low self-efficacy for restricting sodium
      intake. Consistent with these findings, younger participants had a higher median
      sodium intake and higher average adjusted interdialytic weight gain. Females
      reported more problems managing their diet. Race, time on dialysis, and perceived
      income adequacy did not seem to influence outcome measures. CONCLUSION: Our
      findings suggest that patients who are younger and female encounter more
      difficulty adhering to the hemodialysis regimen. Hence, there may be a need to
      individualize counseling and interventions for these individuals. Further
      investigation is needed to understand the independent effects of age and gender
      on adherence to hemodialysis dietary recommendations and perceived self-efficacy.

PMID- 24462499
TI  - Contribution of genetic polymorphisms on functional status at very old age: a
      gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway.
AB  - Preservation of functional ability is a well-recognized marker of longevity. At a
      molecular level, a major determinant of the physiological decline occurring with
      aging is the imbalance between production and accumulation of oxidative damage to
      macromolecules, together with a decreased efficiency of stress response to avoid
      or repair such damage. In this paper we investigated the association of 38 genes
      (311 SNPs) belonging to the pro-antioxidant pathways with physical and cognitive
      performances, by analyzing single SNP and gene-based associations with Hand Grip
      strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental
      State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089
      Danish nonagenarians. Moreover, for each gene analyzed in the pro-antioxidant
      pathway, we tested the influence on longitudinal survival. In the whole sample,
      nominal associations were found for TXNRD1 variability with ADL and WS, NDUFS1
      and UCP3 with HG and WS, GCLC and UCP2 with WS (p<0.05). Stronger associations
      although not holding the multiple comparison correction, were observed between
      MMSE and NDUFV1, MT1A and GSTP1 variability (p<0.009). Moreover, we found that
      association between genetic variability in the pro-antioxidant pathway and
      functional status at old age is influenced by sex. In particular, most
      significant associations were observed in nonagenarian females, between HG scores
      and GLRX and UCP3 variability, between ADL levels and TXNRD1, MMSE and MT1A
      genetic variability. In males, a borderline statistically significant association
      with ADL level was found for UQCRFS1 gene. Nominally significant associations in
      relation to survival were found in the female sample only with SOD2, NDUFS1, UCP3
      and TXNRD1 variability, the latter two confirming previous observations reported
      in the same cohort. Overall, our work supports the evidence that genes belonging
      to the pro-anti-oxidant pathway are able to modulate physical and cognitive
      performance after the ninth decade of life, finally influencing extreme survival.

PMID- 24462500
TI  - Egg number-egg size: an important trade-off in parasite life history strategies.
AB  - Parasites produce from just a few to many eggs of variable size, but our
      understanding of the factors driving variation in these two life history traits
      at the intraspecific level is still very fragmentary. This study evaluates the
      importance of performing multilevel analyses on egg number and egg size, while
      characterising parasite life history strategies. A total of 120 ovigerous females
      of Octopicola superba (Copepoda: Octopicolidae) (one sample (n=30) per season)
      were characterised with respect to different body dimensions (total length;
      genital somite length) and measures of reproductive effort (fecundity; mean egg
      diameter; total reproductive effort; mean egg sac length). While endoparasites
      are suggested to follow both an r- and K-strategy simultaneously, the evidence
      found in this and other studies suggests that environmental conditions force
      ectoparasites into one of the two alternatives. The positive and negative
      skewness of the distributions of fecundity and mean egg diameter, respectively,
      suggest that O. superba is mainly a K-strategist (i.e. produces a relatively
      small number of large, well provisioned eggs). Significant sample differences
      were recorded concomitantly for all body dimensions and measures of reproductive
      effort, while a general linear model detected a significant influence of
      season*parasite total length in both egg number and size. This evidence suggests
      adaptive phenotypic plasticity in body dimensions and size-mediated changes in
      egg production. Seasonal changes in partitioning of resources between egg number
      and size resulted in significant differences in egg sac length but not in total
      reproductive effort. Evidence for a trade-off between egg number and size was
      found while controlling for a potential confounding effect of parasite total
      length. However, this trade-off became apparent only at high fecundity levels,
      suggesting a state of physiological exhaustion. 

PMID- 24462501
TI  - Association of chronic widespread pain with objectively measured physical
      activity in adults: findings from the National Health and Nutrition Examination
      survey.
AB  - Chronic widespread pain (CWP) is a common and potentially debilitating disorder.
      Patterns of physical activity (PA) in adults with CWP have primarily been
      investigated using subjective, self-report measures. The current study sought to
      characterize PA among community-dwelling individuals with CWP, chronic regional
      pain, or no chronic pain using objective measurements obtained via accelerometry
      in the 2003 to 2004 National Health and Nutrition Examination Survey. Data from
      3,952 participants ages 20 and older were analyzed to assess relationships
      between pain status and objective measurements of PA. Prevalence of CWP was 3.3%
      and 5.4% in men and women, respectively. In men and women, the average activity
      counts per minute and time spent in moderate-to-vigorous PA were significantly
      lower for the CWP group than for the no chronic pain group. Interestingly, time
      spent in sedentary, light, and lifestyle activities was not associated with pain
      status. Statistical interaction tests indicated that the effects of chronic pain
      on counts per minute were stronger in men than in women. Despite recommendations
      for increased moderate-to-vigorous PA as a pain management strategy for CWP,
      results from this nationally representative study indicate that adults with CWP
      participate in less moderate-to-vigorous PA than individuals without chronic
      pain. PERSPECTIVE: Using objective measurement of PA in a nationally
      representative sample, this study demonstrates that adults with CWP participate
      in reduced daily and moderate-to-vigorous PA in comparison to people with no
      chronic pain. Findings indicate that clinicians should emphasize the importance
      of increasing PA in patients with CWP.

PMID- 24462503
TI  - Contribution of chemokine CCL2/CCR2 signaling in the dorsal root ganglion and
      spinal cord to the maintenance of neuropathic pain in a rat model of lumbar disc
      herniation.
AB  - Lumbar disc herniation (LDH) is a major cause of sciatica, but the underlying
      mechanisms are not well understood. Chemokine CCL2 has been implicated to play a
      vital role in the neuroinflammation and central sensitization after spinal nerve
      ligation. Here we investigated the expression and the role of CCL2 and its
      receptor CCR2 in LDH-induced pain. Implantation of autologous nucleus pulposus
      induced persistent pain hypersensitivity, associated with increased mRNA
      expression of CCL2 and CCR2 in the dorsal root ganglion and spinal cord.
      Interestingly, CCL2 was increased in neurons and CCR2 was mainly increased in
      macrophages in the dorsal root ganglion, whereas CCL2 and CCR2 were increased in
      astrocytes and neurons, respectively, in the spinal cord. Intrathecal injection
      of CCR2 antagonist RS504393 at 3 days or 10 days significantly attenuated nucleus
      pulposus-induced mechanical allodynia. The results suggest that CCL2/CCR2 in the
      dorsal root ganglion and spinal cord is involved in the maintenance of LDH
      induced pain. Targeting CCL2/CCR2 signaling may be a potential treatment for
      chronic radicular neuropathic pain. PERSPECTIVE: These results suggest that
      CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord is involved in
      LDH-induced pain via distinct mechanisms. These findings provide evidence of the
      antinociceptive effect of CCR2 antagonist on radicular neuropathic pain.

PMID- 24462502
TI  - Activation of cutaneous immune responses in complex regional pain syndrome.
AB  - The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but
      tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are elevated in
      experimental skin blister fluid from CRPS-affected limbs, as is tryptase, a
      marker for mast cells. In the rat fracture model of CRPS, exaggerated sensory and
      sympathetic neural signaling stimulate keratinocyte and mast cell proliferation,
      causing the local production of high levels of inflammatory cytokines leading to
      pain behavior. The current investigation used CRPS patient skin biopsies to
      determine whether keratinocyte and mast cell proliferation occur in CRPS skin and
      to identify the cellular source of the up-regulated TNF-alpha, IL-6, and tryptase
      observed in CRPS experimental skin blister fluid. Skin biopsies were collected
      from the affected skin and the contralateral mirror site in 55 CRPS patients and
      the biopsy sections were immunostained for keratinocyte, cell proliferation, mast
      cell markers, TNF-alpha, and IL-6. In early CRPS, keratinocytes were activated in
      the affected skin, resulting in proliferation, epidermal thickening, and up
      regulated TNF-alpha and IL-6 expression. In chronic CRPS, there was reduced
      keratinocyte proliferation, leading to epidermal thinning in the affected skin.
      Acute CRPS patients also had increased mast cell accumulation in the affected
      skin, but there was no increase in mast cell numbers in chronic CRPS.
      PERSPECTIVE: The results of this study support the hypotheses that CRPS involves
      activation of the innate immune system, with keratinocyte and mast cell
      activation and proliferation, inflammatory mediator release, and pain.

PMID- 24462504
TI  - Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated
      women with early-stage breast cancer.
AB  - Aromatase inhibitors (AIs), which are used to treat breast cancer, inhibit
      estrogen production in postmenopausal women. AI-associated musculoskeletal
      symptoms occur in approximately half of treated women and lead to treatment
      discontinuation in 20 to 30%. The etiology may be due in part to estrogen
      deprivation. In premenopausal women, lower estrogen levels have been associated
      with increased pain as well as with impairment of descending pain inhibitory
      pathways, which may be a risk factor for developing chronic pain. We
      prospectively tested whether AI-induced estrogen deprivation alters pain
      sensitivity, thereby increasing the risk of developing AI-associated
      musculoskeletal symptoms. Fifty postmenopausal breast cancer patients underwent
      pressure pain testing and conditioned pain modulation (CPM) assessment prior to
      AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed
      patients demonstrated impaired CPM, which was greater in those who had previously
      received chemotherapy (P = .006). No statistically significant change in pressure
      pain threshold or CPM was identified following estrogen deprivation. In addition,
      there was no association with either measure of pain sensitivity and change in
      patient-reported pain with AI therapy. AI-associated musculoskeletal symptoms are
      not likely due to decreased pain threshold or impaired CPM prior to treatment
      initiation, or to effects of estrogen depletion on pain sensitivity. PERSPECTIVE:
      This article presents our findings of the effect of estrogen deprivation on
      objective measures of pain sensitivity. In postmenopausal women, medication
      induced estrogen depletion did not result in an identifiable change in pressure
      pain threshold or CPM. Impaired CPM may be associated with chemotherapy.

PMID- 24462506
TI  - Automatic seizure detection in long-term scalp EEG using an adaptive thresholding
      technique: a validation study for clinical routine.
AB  - OBJECTIVE: In a previous study we proposed a robust method for automatic seizure
      detection in scalp EEG recordings. The goal of the current study was to validate
      an improved algorithm in a much larger group of patients in order to show its
      general applicability in clinical routine. METHODS: For the detection of seizures
      we developed an algorithm based on Short Time Fourier Transform, calculating the
      integrated power in the frequency band 2.5-12 Hz for a multi-channel seizure
      detection montage referenced against the average of Fz-Cz-Pz. For identification
      of seizures an adaptive thresholding technique was applied. Complete data sets of
      each patient were used for analyses for a fixed set of parameters. RESULTS: 159
      patients (117 temporal-lobe epilepsies (TLE), 35 extra-temporal lobe epilepsies
      (ETLE), 7 other) were included with a total of 25,278 h of EEG data, 794 seizures
      were analyzed. The sensitivity was 87.3% and number of false detections per hour
      (FpH) was 0.22/h. The sensitivity for TLE patients was 89.9% and FpH=0.19/h; for
      ETLE patients sensitivity was 77.4% and FpH=0.25/h. CONCLUSIONS: The seizure
      detection algorithm provided high values for sensitivity and selectivity for
      unselected large EEG data sets without a priori assumptions of seizure patterns.
      SIGNIFICANCE: The algorithm is a valuable tool for fast and effective screening
      of long-term scalp EEG recordings.

PMID- 24462507
TI  - Radiofrequency ablation of a left lateral atrioventricular accessory pathway in a
      13-year-old boy with a criss-cross heart guided by nonfluoroscopic imaging.
AB  - We present the first description of successful radiofrequency (RF) ablation of a
      bidirectional atrioventricular accessory pathway (AP) guided by nonfluoroscopic
      mapping with use of three-dimensional magnetic resonance imaging integrated into
      the Nav-X system (MRI/Nav-X fusion) in a 13-year-old boy with remote surgical
      palliation for cyanotic criss-cross heart with atrioventricular discordance,
      double-outlet right ventricle, and a large ventricular septal defect. Due to
      complex anatomy, a unique finding was that the eliminated left lateral AP
      electrically connected the left atrium to the antero-superior morphologic right
      ventricle prior to ablation. 

PMID- 24462505
TI  - Multimodal assessment of primary motor cortex integrity following sport
      concussion in asymptomatic athletes.
AB  - OBJECTIVE: Recent studies have shown, in asymptomatic concussed athletes,
      metabolic disruption in the primary motor cortex (M1) and abnormal intracortical
      inhibition lasting for more than six months. The present study aims to assess if
      these neurochemical and neurophysiological alterations are persistent and linked
      to M1 cortical thickness. METHODS: Sixteen active football players who sustained
      their last concussion, on average, three years prior to testing and 14 active
      football players who never sustained a concussion were recruited for a single
      session of proton magnetic resonance spectroscopy ((1)H-MRS) and transcranial
      magnetic stimulation (TMS). Measures of M1 and whole brain cortical thickness
      were acquired, and (1)H-MRS data were acquired from left M1 using a MEGA-PRESS
      sequence. Cortical silent period (CSP) and long-interval intracortical inhibition
      (LICI) were measured with TMS applied over left M1. RESULTS: No significant group
      differences were observed for metabolic concentrations, TMS measures, and
      cortical thickness. However, whereas GABA and glutamate levels were positively
      correlated in control athletes, this relationship was absent in concussed
      athletes. CONCLUSION: These data suggest the general absence of neurophysiologic,
      neurometabolic and neuroanatomical disruptions in M1 three years following the
      last concussive event. However, correlational analyses suggest the presence of a
      slight metabolic imbalance between GABA and glutamate concentrations in the
      primary motor cortex of concussed athletes. SIGNIFICANCE: The present study
      highlights the importance of multimodal assesments of the impacts of sport
      concussions.

PMID- 24462508
TI  - Evaluation of pharmacological interactions after administration of a levamisole,
      albendazole and ivermectin triple combination in lambs.
AB  - The goals of the current trial were (a) to characterize the plasma disposition
      kinetics of levamisole (LEV), albendazole (ABZ) and ivermectin (IVM), each
      administered either alone (single active ingredient) or as a combined formulation
      to lambs; (b) to compare the clinical anthelmintic efficacy of the same drugs
      given either separately or co-administered to lambs infected with resistant
      nematodes. Fifty Corriedale lambs naturally infected with multiple resistant
      gastrointestinal nematodes were involved in the following experimental trials:
      (a) "Pharmacokinetic trial": the animals were allocated into five groups (n=10
      each) and intraruminally treated with either LEV (8 mg/kg), ABZ (5mg/kg), IVM
      (0.2mg/kg), or with a LEV+ABZ+IVM combined formulation, where each active
      ingredient was administered at the same dose. Blood samples were collected over
      15 days post-treatment and drug plasma concentrations measured by HPLC. (b)
      "Efficacy trial": the same treated groups plus an untreated control group were
      used to assess the comparative anthelmintic efficacy by the faecal egg count
      reduction test (FECRT). Although the overall LEV disposition kinetics was
      unaffected, significantly lower (61%) ABZ-sulphoxide and higher (71%) IVM
      systemic availabilities were obtained after administration of the combined
      formulation in comparison to those obtained after treatment with each drug alone.
      A multiple drug resistance situation was observed for Haemonchus spp. The
      observed efficacies were 52% (LEV), 72% (ABZ), 80% (IVM) and 87% (triple combined
      formulation). The results reported here contribute to the pharmaco-therapeutic
      knowledge on drug combinations. This type of research is crucial before further
      development of combined anthelmintic preparations reaches the market to deal with
      resistant nematode control. The co-administration of LEV+ABZ+IVM did not result
      in a significant advantageous anthelmintic effect compared to the treatment with
      IVM alone. The simultaneous/combined administration of LEV, ABZ and IVM may
      account for a drug-drug pharmacological interaction in infected lambs. The
      pharmacokinetic interaction accounted for a reduced ABZ-sulphoxide and enhanced
      IVM systemic exposure following the combined treatment.

PMID- 24462509
TI  - The anthelmintic efficacy of natural plant cysteine proteinases against two
      rodent cestodes Hymenolepis diminuta and Hymenolepis microstoma in vitro.
AB  - Little is known about the efficacy of cysteine proteinases (CP) as anthelmintics
      for cestode infections. We examined the effects of CPs on two rodent cestodes,
      Hymenolepis diminuta and H. microstoma in vitro. Our data showed that naturally
      occurring mixtures of CPs, such as those found in papaya latex, and relatively
      pure preparations of fruit bromelain, papain and stem bromelain, were active in
      vitro against both juvenile, artificially excysted scoleces, as well as against
      adult worms of both rodent cestodes. Significant dose-dependent reduction in
      motility, ultimately leading to death of the worms, was observed with both
      species, and against both freshly excysted scoleces and 14-day old pre-adult
      worms. The most effective was fruit bromelain (after 30 min of incubation of
      juvenile H. diminuta and H. microstoma IC50=63 and 74 MUM, respectively, and for
      pre-adult worms=199 and 260 MUM, respectively). The least effective was stem
      bromelain (after 30 min of incubation of juvenile H. diminuta and H. microstoma
      IC50=2855 and 2772 MUM, respectively, and for pre-adult worms=1374 and 1332 MUM,
      respectively) and the efficacies of papaya latex supernatant and papain were
      between these extremes. In all cases these values are higher than those reported
      previously for efficacy of CPs against intestinal nematodes, and in contrast to
      nematodes, all CPs were effective against cestodes in the absence of exogenous
      cysteine in incubation media. The CPs appeared to attack the tegument resulting
      in generalised erosion mainly on the strobila. The scolex was more resistant to
      CP attack but nevertheless some damage to the tegument on the scolex was
      detected.

PMID- 24462510
TI  - Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma.
AB  - Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to
      developing targeted diagnostics and therapies for this deadly disease. The
      landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic
      gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs
      including large-scale insertions, deletions, inversions and translocations based
      on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues.
      We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting
      chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating
      mutations and deletions in 10% of cohort. Integrative analysis identified a
      pattern of paired intra-chromosomal translocations flanking focal amplifications
      and asymmetrical patterns of copy number variation flanking breakpoints of
      translocations. Furthermore, we predicted 260 gene fusions which frequently
      result in aberrant over-expression of the 3' genes in tumors and validated 18
      gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. 

PMID- 24462511
TI  - Survival benefit from transplantation in patients listed for heart
      transplantation in the United States.
AB  - OBJECTIVES: The aim of this study was to assess the survival benefit from heart
      transplantation (HT), defined as reduction in the risks for 90-day and 1-year
      mortality on undergoing HT close to listing, in candidates stratified by their
      risk for waiting list mortality. BACKGROUND: Among patients listed for HT, those
      at higher risk for death without transplantation are also at higher risk for
      early post-transplantation mortality. METHODS: All patients age >=18 years listed
      for HT in the United States from 2007 to 2010 were analyzed. A model was
      developed to predict the risk for waiting list mortality within 90 days, and
      listed patients were stratified into 10 risk groups (deciles). All groups were
      followed for 1 year to assess cumulative 1-year mortality while on the waiting
      list. Models of 90-day and 1-year post-transplantation mortality were developed
      using recipient data, and these risks were estimated at listing in all listed
      candidates. RESULTS: Of 10,159 patients listed for HT, 596 (5.9%) died within 90
      days and 1,054 (10.4%) within 1 year without undergoing transplantation. Of 5,720
      recipients of transplants with 1-year follow-up, 576 (10.1%) died within 1 year.
      The risk for death while on the waiting list within 90 days increased from 1.6%
      to 19% across the 10 risk groups. The survival benefit from HT increased
      progressively with higher risk for death without transplantation (p < 0.001 for
      trend), but there was no benefit in the first 6 risk groups. CONCLUSIONS: The
      risk for waiting list mortality varies considerably among HT candidates. Although
      the survival benefit of HT generally increases with increasing risk for waiting
      list mortality, there is no measurable benefit in many candidates at the lower
      end of the risk spectrum.

PMID- 24462512
TI  - Urocortin 3 expression at baseline and during inflammation in the colon:
      corticotropin releasing factor receptors cross-talk.
AB  - Urocortins (Ucn1-3), members of the corticotropin-releasing factor (CRF) family
      of neuropeptides, are emerging as potent immunomodulators. Localized, cellular
      expression of Ucn1 and Ucn2, but not Ucn3, has been demonstrated during
      inflammation. Here, we investigated the role of Ucn3 in a rat model of Crohn's
      colitis and the relative contribution of CRF receptors (CRF1 and CRF2) in
      regulating Ucn3 expression at baseline and during inflammation. Ucn3 mRNA and
      peptide were ubiquitously expressed throughout the GI tract in naive rats. Ucn3
      immunoreactivity was seen in epithelial cells and myenteric neurons. On day 1 of
      colitis, Ucn3 mRNA levels decreased by 80% and did not recover to baseline even
      by day 9. Next, we ascertained pro- or anti-inflammatory actions of Ucn3 during
      colitis. Surprisingly, unlike observed anti-inflammatory actions of Ucn1,
      exogenous Ucn3 did not alter histopathological outcomes during colitis and
      neither did it alter levels of pro-inflammatory cytokines IL-6 and TNF-alpha. At
      baseline, colon-specific knockdown of CRF1, but not CRF2 decreased Ucn3 mRNA by
      78%, whereas during colitis, Ucn3 mRNA levels increased after CRF1 knockdown. In
      cultured cells, co-expression of CRF1+CRF2 attenuated Ucn3-stimulated
      intracellular Ca(2+) peak by 48% as compared to cells expressing CRF2 alone.
      Phosphorylation of p38 kinase increased by 250% during colitis and was
      significantly attenuated after Ucn3 administration. Thus, our results suggest
      that a balanced and coordinated expression of CRF receptors is required for
      proper regulation of Ucn3 at baseline and during inflammation. 

PMID- 24462513
TI  - Early surgical thrombectomy improves salvage of thrombosed vascular accesses.
AB  - OBJECTIVE: The timing and urgency of salvage attempts for acutely thrombosed
      hemodialysis vascular accesses remain poorly defined. We examined the outcome of
      early surgical thrombectomy after acute access thrombosis to assess the influence
      of expedited timing on access salvage. METHODS: Between January 2007 and October
      2012, 114 surgical thrombectomy attempts were performed on 82 patients to salvage
      89 accesses. The time between the diagnosis of thrombosis and admission to the
      operative suite (T1), the time between diagnosis and the following dialysis
      session (T2), and clinical and biologic parameters were collected prospectively.
      Data were retrospectively compared between the early (T1 <6 hours) and later (T1
      >6 hours) treatment groups. The main outcome measure was technical success.
      Kaplan-Meier survival analysis was used to estimate functional patency rates.
      RESULTS: Mean patient follow-up was 22 +/- 18 months. The mean time from referral
      to procedure (T1) was 5.7 +/- 4.5 hours. The mean time T1 was 3.6 +/- 1.2 hours
      in the early group and 10.3 +/- 5.4 hours in the later group. The mean time to
      dialysis (T2) was 14.3 +/- 6.5 hours in the early group and 23.9 +/- 9.4 hours in
      the later group. Thrombectomy performed <= 6 hours after diagnosis (T1 <6 hours)
      had significantly higher technical success of 86% compared with 69% for
      thrombectomy performed later (T1 >6 hours; P = .04). The two groups did not
      differ significantly in patient comorbidities, type of access, or adjunctive
      procedures performed (P >= .1). At 12 months, the primary patency rate for all
      index cases, including technical failures, was 55% +/- 7.1% in the early group
      and 33% +/- 9.7% in the later group (P = .13). The secondary patency rate was 67%
      +/- 6.8% in the early group and 50% +/- 9.9% in the later group (P = .05).
      CONCLUSIONS: After acute access thrombosis, early surgical thrombectomy was
      associated with higher technical success and potentially improved midterm
      patency.

PMID- 24462514
TI  - Comparison of military and civilian popliteal artery trauma outcomes.
AB  - OBJECTIVE: Popliteal artery injury has historically led to high amputation rates
      in both the military and civilian setting. Military and civilian popliteal injury
      patterns differ in mechanism and severity of injury, prompting us to compare
      modern management and report differences in outcomes between these two patient
      groups. We hypothesized that whereas amputation rates may be higher in the
      military, this would correlate with worse overall injury severity. METHODS:
      Military casualties from 2003-2007 with a popliteal artery injury identified from
      the Joint Theater Trauma Registry were compared retrospectively with civilian
      patients presenting to a single level I institution from 2002-2009 with popliteal
      arterial injury. Demographics, mechanism of injury, coinjuries, Injury Severity
      Score (ISS), Mangled Extremity Severity Scores (MESS), interventions, and
      secondary amputation rates were reviewed. Descriptive statistics and unpaired t
      tests were used to compare data. Statistical significance was P < .05. RESULTS:
      The study group of 110 patients consisted of 46 (41.8%) military and 64 (58.2%)
      civilians with 48 and 64 popliteal artery injuries, respectively. The military
      population was younger (28 vs 35 years; P < .004), entirely male (46 [100%] vs 51
      [80%]; P < .0001), and had more penetrating injuries (44 [96%] vs 19 [30%]; P <
      .0001). ISS (18.7 vs 13.9; P < .005) and MESS (7.3 vs 5.1; P < .0001) were higher
      in the military group. Limb revascularizations in both military and civilian
      populations were mostly by autogenous bypass (65% vs 77%) followed by primary
      repair (26% vs 16%), covered stent (0% vs 6%), or other procedure (ligation
      and/or thrombectomy) (9% vs 1%). Fasciotomy (20 [42%] vs 37 [58%]; P = .14),
      compartment syndrome (10 [21%] vs 15 [23%]; P = .84), and concomitant venous
      repair rates (14 [29%] vs 15 [23%]; P = .42) were not different between cohorts.
      There was no difference in the fracture rate (26 [54%] vs 41 [64%]; P = .43), but
      the civilian group had a higher rate of dislocation (1 [2%] vs 19 [30%]; P <
      .0001). Secondary amputation rates were significantly higher in the military (14
      [29%] vs 8 [13%]; P < .03). CONCLUSIONS: Although both civilian and military
      cohorts have high amputation rates for popliteal arterial injury, the rate of
      amputation appears to be higher in the military and is associated with a
      penetrating mechanism of injury primarily from improvised explosive devices
      resulting in a higher MESS and ISS.

PMID- 24462515
TI  - Successful right ventricular mechanical support after combined heart-liver
      transplantation.

PMID- 24462516
TI  - Successful Perioperative Management of Severe Bleeding From Undiagnosed Acquired
      Factor VIII Inhibitors.

PMID- 24462517
TI  - The utility of atrioventricular pacing via pulmonary artery catheter during
      transcatheter aortic valve replacement.

PMID- 24462518
TI  - DNA damage responsive microRNAs misexpressed in human cancer modulate therapy
      sensitivity.
AB  - The DNA damage response (DDR) is activated upon DNA damage and prevents
      accumulation of mutations and chromosomal rearrangements, both driving
      carcinogenesis. Tumor cells often have defects in the DDR, which in combination
      with continuous cell proliferation are exploited by genotoxic cancer therapies.
      Most cancers, overcome initial sensitivity and develop drug resistance, e.g. by
      modulation of the DDR. Not much is known, however, about DNA damage responsive
      microRNAs in cancer therapy resistance. Therefore, we mapped temporal microRNA
      expression changes in primary breast epithelial cells upon low and high dose
      exposure to the DNA damaging agents ionizing radiation and cisplatin. A third of
      all DDR microRNAs commonly regulated across all treatments was also misexpressed
      in breast cancer, indicating a DDR defect. We repeated this approach in primary
      lung epithelial cells and non-small cell lung cancer samples and found that more
      than 40% of all DDR microRNAs was deregulated in non-small cell lung cancer.
      Strikingly, the microRNA response upon genotoxic stress in primary breast and
      lung epithelial cells was markedly different, although the biological outcome of
      DNA damage signaling (cell death/senescence or survival) was similar. Several DDR
      microRNAs deregulated in cancer modulated sensitivity to anti-cancer agents. In
      addition we were able to distinguish between microRNAs that induced resistance by
      potentially inducing quiescence (miR-296-5p and miR-382) or enhancing DNA repair
      or increased DNA damage tolerance (miR-21). In conclusion, we provide evidence
      that DNA damage responsive microRNAs are frequently misexpressed in human cancer
      and can modulate chemotherapy sensitivity. 

PMID- 24462519
TI  - Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell
      polarity Par3 protein.
AB  - High-risk human papillomavirus (HPV) infection is the principal risk factor for
      the development of cervical cancer. The HPV E6 oncoprotein has the ability to
      target and interfere with several PSD-95/DLG/ZO-1 (PDZ) domain-containing
      proteins that are involved in the control of cell polarity. This function can be
      significant for E6 oncogenic activity because a deficiency in cell polarisation
      is a marker of tumour progression. The establishment and control of polarity in
      epithelial cells depend on the correct asymmetrical distribution of proteins and
      lipids at the cell borders and on specialised cell junctions. In this report, we
      have investigated the effects of HPV E6 protein on the polarity machinery, with a
      focus on the PDZ partitioning defective 3 (Par3) protein, which is a key
      component of tight junctions (TJ) and the polarity network. We demonstrate that
      E6 is able to bind and induce the mislocalisation of Par3 protein in a PDZ
      dependent manner without significant reduction in Par3 protein levels. In
      addition, the high-risk HPV-18 E6 protein promotes a delay in TJ formation when
      analysed by calcium switch assays. Taken together, the data presented in this
      study contribute to our understanding of the molecular mechanism by which HPVs
      induce the loss of cell polarity, with potential implications for the development
      and progression of HPV-associated tumours. 

PMID- 24462520
TI  - DNA polymerase beta deficiency is linked to aggressive breast cancer: a
      comprehensive analysis of gene copy number, mRNA and protein expression in
      multiple cohorts.
AB  - Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and
      amplifications in breast cancer. Although such genetic changes may have
      phenotypic consequences, the identity of candidate gene(s) remains to be clearly
      defined. Pol beta gene is localized to chromosome 8p12-p11 and encodes a key DNA
      base excision repair protein. Pol beta may be a tumour suppressor and involved in
      breast cancer pathogenesis. We conducted the first and the largest study to
      comprehensively evaluate pol beta in breast cancer. We investigated pol beta gene
      copy number changes in two cohorts (n = 128 &n = 1952), pol beta mRNA expression
      in two cohorts (n = 249 &n = 1952) and pol beta protein expression in two cohorts
      (n = 1406 &n = 252). Artificial neural network analysis for pol beta interacting
      genes was performed in 249 tumours. For mechanistic insights, pol beta gene copy
      number changes, mRNA and protein levels were investigated together in 128 tumours
      and validated in 1952 tumours. Low pol beta mRNA expression as well as low pol
      beta protein expression was associated high grade, lymph node positivity,
      pleomorphism, triple negative, basal-like phenotypes and poor survival (ps <
      0.001). In oestrogen receptor (ER) positive sub-group that received tamoxifen,
      low pol beta protein remains associated with aggressive phenotype and poor
      survival (ps < 0.001). Artificial neural network analysis revealed ER as a top
      pol beta interacting gene. Mechanistically, there was strong positive correlation
      between pol beta gene copy number changes and pol beta mRNA expression (p <
      0.0000001) and between pol beta mRNA and pol beta protein expression (p <
      0.0000001). This is the first study to provide evidence that pol beta deficiency
      is linked to aggressive breast cancer and may have prognostic and predictive
      significance in patients.

PMID- 24462522
TI  - Calcium hydroxylapatite injection for the patulous Eustachian tube.
AB  - The function of the E-tube is to adjust the balance of both sides of the ear
      drum. The patulous Eustachian tube (PET) is a rare disease and a benign
      condition. So, most of the doctors ignored this disease. But, patients with PET
      suffer from ear fullness, autophony, hearing their own breathing, and etc. Many
      treatment methods have been introduced and injection is also one way of treating
      the disease. We introduce an injection technique for the treatment of PET using
      calcium hydroxylapatitie (Radiesse(r)). 

PMID- 24462521
TI  - TP53 mutation-correlated genes predict the risk of tumor relapse and identify
      MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers.
AB  - Breast cancers (BC) carry a complex set of gene mutations that can influence
      their gene expression and clinical behavior. We aimed to identify genes driven by
      the TP53 mutation status and assess their clinical relevance in estrogen receptor
      (ER)-positive and ER-negative BC, and their potential as targets for patients
      with TP53 mutated tumors. Separate ROC analyses of each gene expression according
      to TP53 mutation status were performed. The prognostic value of genes with the
      highest AUC were assessed in a large dataset of untreated, and neoadjuvant
      chemotherapy treated patients. The mitotic checkpoint gene MPS1 was the most
      significant gene correlated with TP53 status, and the most significant prognostic
      marker in all ER-positive BC datasets. MPS1 retained its prognostic value
      independently from the type of treatment administered. The biological functions
      of MPS1 were investigated in different BC cell lines. We also assessed the
      effects of a potent small molecule inhibitor of MPS1, SP600125, alone and in
      combination with chemotherapy. Consistent with the gene expression profiling and
      siRNA assays, the inhibition of MPS1 by SP600125 led to a reduction in cell
      viability and a significant increase in cell death, selectively in TP53-mutated
      BC cells. Furthermore, the chemical inhibition of MPS1 sensitized BC cells to
      conventional chemotherapy, particularly taxanes. Our results collectively
      demonstrate that TP53-correlated kinase MPS1, is a potential therapeutic target
      in BC patients with TP53 mutated tumors, and that SP600125 warrant further
      development in future clinical trials. 

PMID- 24462523
TI  - QRS fusion complex analysis using wave interference to predict reverse remodeling
      during cardiac resynchronization therapy.
AB  - BACKGROUND: Biventricular (BV) electrical wavefront fusion can induce improvement
      in left ventricular (LV) size and function during cardiac resynchronization
      therapy (CRT). Changes in BV wave propagation sequence and duration register in
      the QRS complex on the standard electrocardiogram. We developed a wave
      interference method for the characterization of BV fusion to predict LV reverse
      remodeling. OBJECTIVE: To develop a simple electrocardiographic method for
      predicting reverse remodeling during CRT. METHODS: QRS complexes during left
      bundle branch block (LBBB) and CRT were analyzed in 375 patients with ejection
      fraction <=35% and New York Heart Association class III-IV (Leiden study: n =
      226) as well as in patients with ejection fraction <=40% and New York Heart
      Association class I-II (REVERSE trial: n = 149) for predictors of >=10% reduction
      in left ventricular end-systolic volume at 6 months. CRT-induced changes in
      ventricular activation (QRS fusion contour), electrical asynchrony (QRS
      difference = BV-paced QRS - LBBB QRS, in milliseconds), and LBBB substrate (LV
      activation time and QRS score for LV scar) were quantified. RESULTS:
      Multivariable predictors of reverse remodeling were as follows: (1) either of 2
      BV fusion patterns: QRS normalization in leads V1 and V2 (n = 66 [18%]; odds
      ratio [OR] 3.71; 95% confidence interval [CI] 1.26-10.94) or a new or an
      increased R wave in leads V1-V2 (n = 267 [71%]; OR 1.55; 95% CI 0.65-3.65); (2)
      QRS difference <= -25 ms (OR 2.35; 95% CI 1.12-4.91); and (3) good substrate (low
      to moderate QRS score and LV activation time >=110 ms; OR 2.94; 95% CI 1.68
      5.14). Remodeling rates were 40% for poor substrate and persistent LBBB QRS
      complex (absent BV fusion; QRS type 3: n = 42 [11%]) and 97% for the best BV QRS
      fusion pattern and greater reduction in electrical asynchrony (larger QRS
      difference). CONCLUSION: Easily determined QRS complex attributes before and
      after CRT predict LV reverse remodeling.

PMID- 24462524
TI  - LAA ligation using the LARIAT suture delivery device: tips and tricks for a
      successful procedure.

PMID- 24462525
TI  - Adult exposure to the synthetic hormone 17alpha-ethynylestradiol affects
      offspring of the gastropods Nassarius burchardi and Nassarius jonasii.
AB  - The aim of this study was to determine whether adult exposure to endocrine
      disrupting compounds affects offspring using trans-generational testing. Adult
      estuarine dwelling gastropods Nassarius burchardi and Nassarius jonasii were
      exposed to the synthetic estrogen 17alpha-ethynylestradiol (EE2) to determine the
      effects on the development and survival of their offspring. Adults were
      maintained in synthetic seawater controls and EE2 treatments (0.005, 0.05, 0.5,
      50ug/L) over a sixteen week period. Egg capsules were collected from the adults
      following four, ten and sixteen weeks of adult exposure and transferred to
      different EE2 exposure scenarios. Treatment concentrations were selected to
      represent changes in EE2 exposure that could occur over different periods in an
      organism's lifecycle. Egg capsules laid by adults were therefore transferred to
      control or EE2 treatments (0.005, 0.05, 0.5, 5, 50, 500ug/L) to develop until
      hatching. The percentage of egg capsules with unviable eggs and abnormalities,
      number of days for hatching to occur and hatching success were measured. The
      veliger larvae that hatched from egg capsules following two, eight and fourteen
      weeks of adult exposure to EE2 and controls were used in 96h acute toxicity tests
      with controls and EE2 treatments at concentrations of 0.5, 5, 50, 500, 1250,
      2500, 4000ug/L. Exposure of adult N. burchardi and N. jonasii to EE2 affected the
      percentage of egg capsules with unviable eggs, the development and hatching
      success of embryos and survival of veligers. These toxicity tests produced a
      complex set of results with different responses in developing eggs and veliger
      larvae to the adult EE2 treatments and length of adult exposure. This study
      demonstrates the importance of trans-generational testing and adult exposure
      scenarios in toxicity investigations. 

PMID- 24462526
TI  - Absence of detectable inositol hexakisphosphate (phytate) in plasma.
AB  - A critical evaluation of a recent attempt to measure inositol hexakisphosphate
      (IP6) in mammalian plasma by mass spectroscopy leads to the conclusion that as
      yet there is no unambiguous evidence that plasma contains any IP6.

PMID- 24462527
TI  - Characterization of an extremely thermostable but cold-adaptive beta
      galactosidase from the hyperthermophilic archaeon Pyrococcus furiosus for use as
      a recombinant aggregation for batch lactose degradation at high temperature.
AB  - beta-Galactosidase (lactase), which catalyzes the hydrolysis of lactose into
      glucose and galactose, is one of the most important enzymes used in dairy
      processing. In this study, a gene that encoded an extremely thermostable beta
      galactosidase from Pyrococcus furiosus (Pflactase) was cloned and expressed in
      Escherichia coli BL21. The recombinant enzyme was purified by heat treatment and
      Ni-NTA affinity chromatography. The enzyme displayed optimal activity at 90
      degrees C and pH 7.0 in phosphate buffer. The specific activity of the
      recombinant enzyme on o-nitrophenyl-beta-d-galactopyranoside was 10.2 U/mg at 0
      degrees C and 130.0dU/mg at 90 degrees C. The half-lives of the enzyme were
      31423.4, 8168.3, 4017.7, 547.4, 309.6, and 203.5 min at 70 degrees C, 80 degrees
      C, 85 degrees C, 90 degrees C, 95 degrees C, and 100 degrees C, respectively. The
      recombinant enzyme exhibited both beta-galactosidase and beta-glucosidase
      activity. The active inclusion bodies of beta-galactosidase were easily isolated
      by nonionic detergent treatment and directly used for lactose conversion in a
      repetitive batch mode. More than 54% (90 degrees C) or 88% (10 degrees C) of the
      original enzyme activity was retained after 10 conversion cycles under optimum
      conditions. These results suggest that the recombinant thermostable beta
      galactosidase may be suitable for the hydrolysis of lactose in milk processing. 

PMID- 24462528
TI  - Text messaging-based smoking cessation intervention: a narrative review.
AB  - INTRODUCTION: Smoking cessation interventions delivered via text messaging on
      mobile phones may enhance motivations to quit smoking. The goal of this narrative
      review is to describe the text messaging interventions' theoretical contents,
      frequency and duration, treatment outcome, and sample characteristics such as age
      and motivation to quit, to better inform the future development of this mode of
      intervention. METHODS: Studies were included if text messaging was primarily used
      to deliver smoking cessation intervention and published in English in a peer
      reviewed journal. All articles were coded by two independent raters to determine
      eligibility and to extract data. RESULTS: Twenty-two studies described 15 text
      messaging interventions. About half of the interventions recruited adults (ages
      30-40) and the other half targeted young adults (ages 18-29). Fourteen
      interventions sent text messages during the quit phase, 10 had a preparation
      phase and eight had a maintenance phase. The number of text messages and the
      duration of the intervention varied. All used motivational messages grounded in
      social cognitive behavioral theories, 11 used behavioral change techniques, and
      14 used individually tailored messages. Eleven interventions also offered other
      smoking cessation tools. Three interventions yielded smoking cessation outcomes
      greater than the control condition. CONCLUSIONS: The proliferation of text
      messaging in recent years suggests that text messaging interventions may have the
      potential to improve smoking cessation rates. Detailed summary of the
      interventions suggests areas for future research and clinical application. More
      rigorous studies are needed to identify components of the interventions that can
      enhance their acceptability, feasibility and efficacy.

PMID- 24462529
TI  - Becoming a clinician-educator: lessons learned.

PMID- 24462530
TI  - Consensus statements on the risk, prevention, and treatment of venous
      thromboembolism in inflammatory bowel disease: Canadian Association of
      Gastroenterology.
AB  - BACKGROUND & AIMS: Guidelines for the management of venous thromboembolism (VTE)
      from the American College of Chest Physicians do not address patients with
      inflammatory bowel disease (IBD), a group with a high risk of both VTE and
      gastrointestinal bleeding. We present recommendations for the prevention and
      treatment of VTE in patients with IBD. METHODS: A systematic literature search
      was performed to identify studies on VTE in IBD. The quality of evidence and
      strength of recommendations were rated according to the Grading of Recommendation
      Assessment, Development, and Evaluation (GRADE) approach. Statements were
      developed through an iterative online platform, then finalized and voted on by a
      working group of adult and pediatric gastroenterologists and thrombosis
      specialists. RESULTS: IBD patients have an approximately 3-fold higher risk of
      VTE compared with individuals without IBD, and disease flares further increase
      this risk. Anticoagulant thromboprophylaxis is recommended for IBD patients who
      are hospitalized with IBD flares without active bleeding and is suggested when
      bleeding is nonsevere. Anticoagulant thromboprophylaxis is suggested during
      moderate-severe IBD flares in outpatients with a history of VTE provoked by an
      IBD flare or an unprovoked VTE, but not otherwise. The recommended duration of
      anticoagulation after a first VTE is based on the presence of provoking factors.
      Specific suggestions are made for the prevention and treatment of VTE in
      pediatric and pregnant IBD patients. CONCLUSIONS: Using the American College of
      Chest Physicians' guidelines as a foundation, we have integrated evidence from
      IBD studies to develop specific recommendations for the management of VTE in this
      high-risk population.

PMID- 24462531
TI  - Clinical adjacent-segment pathology after anterior cervical discectomy and
      fusion: results after a minimum of 10-year follow-up.
AB  - BACKGROUND CONTEXT: Anterior cervical discectomy and fusion using cervical plates
      has been seen as effective at relieving cervical radiculopathy and myelopathy
      symptoms. Although it is commonly used, subsequent disc degeneration at levels
      adjacent to the fusion remains an important problem. However, data on the
      frequency, impact, and predisposing factors for this pathology are still rare.
      PURPOSE: To evaluate the incidence, predisposing factors, and impact of
      radiographic and clinical adjacent-segment pathologies after anterior cervical
      discectomy and fusion using cervical plates and to analyze the efficacy of this
      surgical method over the long term, after a minimum follow-up period of 10 years.
      STUDY DESIGN: Retrospective clinical study. PATIENT SAMPLE: Our study was a
      retrospective analysis of 177 patients who underwent anterior cervical discectomy
      and fusion using cervical plates, with follow-up periods of at least 10 years
      (mean 16.2 years). OUTCOME MEASURES: Radiographic adjacent-segment pathology
      using plain radiographs and clinical adjacent-segment pathology after anterior
      cervical discectomy and fusion using cervical plates. METHODS: We defined a new
      grading system of plain radiographic evidence of degenerative changes in adjacent
      discs after anterior cervical discectomy and fusion using cervical plates; Grade
      0 is considered normal, and Grade V consists the presence of posterior
      osteophytes and a decrease in disc height to less than 50% of normal. The
      incidence, predisposing factors, and impact of radiographic and clinical adjacent
      segment pathologies were analyzed according to etiologies, number of fused
      segments, and plate-to-disc distance. RESULTS: Radiographic and clinical adjacent
      segment pathologies were found in 92.1% and 19.2%, respectively, of patients. By
      etiology, clinical adjacent-segment pathology was observed in 13.5% of patients
      who had sustained trauma, 12.7% of those with disc herniation, and 33.3% of those
      with spondylosis. By number of fused segments, clinical adjacent-segment
      pathology was found in 13.2% of patients who underwent single-level fusion and in
      32.1% of those who underwent multilevel fusion surgeries. Patients with a plate
      to-disc distance of less than 5 mm, who had spondylosis, or who underwent
      multilevel fusion had a higher incidence of clinical adjacent-segment pathology
      after anterior cervical discectomy and fusion using cervical plates than other
      groups did (p<.05). Of all patients, only 6.8% needed follow-up surgery.
      CONCLUSIONS: We found that over the long term, at a minimum follow-up point of 10
      years, a plate-to-disc distance of less than 5 mm, having spondylosis, and
      undergoing multilevel fusion were predisposing factors for the occurrence of
      clinical adjacent-segment pathology. Nevertheless, the incidence of clinical
      findings of adjacent-segment pathology was much lower than the incidence of
      radiographic findings. Also, the rate of follow-up surgery was low. Therefore,
      anterior cervical discectomy and fusion using cervical plates can be considered a
      safe and effective procedure.

PMID- 24462532
TI  - A primer for workers' compensation.
AB  - BACKGROUND CONTEXT: A physician's role within a workers' compensation injury
      extends far beyond just evaluation and treatment with several socioeconomic and
      psychological factors at play compared with similar injuries occurring outside of
      the workplace. Although workers' compensation statutes vary among states, all
      have several basic features with the overall goal of returning the injured worker
      to maximal function in the shortest time period, with the least residual
      disability and shortest time away from work. PURPOSE: To help physicians
      unfamiliar with the workers' compensation process accomplish these goals. STUDY
      DESIGN: Review. METHODS: Educational review. RESULTS: The streamlined review
      addresses the topics of why is workers' compensation necessary; what does
      workers' compensation cover; progression after work injury; impairment and
      maximum medical improvement, including how to use the sixth edition of American
      Medical Association's (AMA) Guides to the evaluation of permanent impairment
      (Guides); completion of work injury claim after impairment rating; independent
      medical evaluation; and causation. CONCLUSIONS: In the "no-fault" workers'
      compensation system, physicians play a key role in progressing the claim along
      and, more importantly, getting the injured worker back to work as soon as safely
      possible. Physicians should remain familiar with the workers' compensation
      process, along with how to properly use the AMA Guides.

PMID- 24462533
TI  - Psoriatic spondylitis.

PMID- 24462534
TI  - Ischemic stroke after cervical spine injury: analysis of 11,005 patients using
      the Japanese Diagnosis Procedure Combination database.
AB  - BACKGROUND CONTEXT: The incidence and relevant risk of ischemic stroke after
      cervical spine trauma remain unknown. PURPOSE: To examine the incidence of
      ischemic stroke during hospitalization in patients with cervical spine injury,
      and analyze the impact of different types of cervical spine injuries on the
      occurrence of ischemic stroke. STUDY DESIGN: Retrospective analysis of data
      abstracted from the Diagnosis Procedure Combination database, a nationally
      representative database in Japan. PATIENT SAMPLE: We included all patients
      hospitalized for any of the following traumas: fracture of cervical spine
      (International Classification of Diseases, 10th Revision codes: S120, S121, S122,
      S127, S129); dislocation of cervical spine (S131, S133); and cervical spinal cord
      injury (SCI) (S141). OUTCOME MEASURES: Outcome measures included all-cause in
      hospital mortality and incidence of ischemic stroke (I63) during hospitalization.
      METHODS: We analyzed the effects of age, sex, comorbidities, smoking status,
      spinal surgery, consciousness level at admission, and type of cervical spine
      injury on outcomes. RESULTS: We identified 11,005 patients with cervical spine
      injury (8,031 men, 2,974 women; mean [standard deviation] age, 63.5 [18] years).
      According to the types of cervical spine injury, we stratified the patients into
      three groups: cervical fracture and/or dislocation without SCI (2,363 patients);
      cervical fracture and/or dislocation associated with SCI (1,283 patients); and
      cervical SCI without fracture and/or dislocation (7,359 patients). Overall,
      ischemic stroke occurred in 115 (1.0%) patients during hospitalization (median
      length of stay, 26 days). In-hospital death occurred in 456 (4.1%) patients.
      Multivariate analyses showed that ischemic stroke after cervical spine injury was
      significantly associated with age, diabetes, and consciousness level at
      admission. The highest in-hospital mortality was observed in patients with
      cervical fracture and/or dislocation associated with SCI (7.6%), followed by
      cervical SCI without fracture and/or dislocation (4.0%), and cervical fracture
      and/or dislocation without SCI (2.6%). Unlike mortality, risks of stroke did not
      vary significantly among the three groups. CONCLUSIONS: This analysis revealed
      that ischemic stroke after cervical spine injury was not uncommon and was
      associated with increased mortality and morbidity. Occurrence of ischemic stroke
      was significantly associated with age, comorbidities such as diabetes, and
      consciousness level at admission, but not with the type of spine injury.

PMID- 24462535
TI  - Intracranial hypotension secondary dislocation of the cervical spine.

PMID- 24462536
TI  - Comparison of radiological and clinical results of balloon kyphoplasty according
      to anterior height loss in the osteoporotic vertebral fracture.
AB  - BACKGROUND CONTEXT: Percutaneous kyphoplasty is effective for pain reduction and
      vertebral height restoration in patients with osteoporotic vertebral fractures.
      However, in cases of severely collapsed fractures involving the loss of more than
      70% of the vertebral height, kyphoplasty is technically difficult to perform and
      the outcomes remain unknown. PURPOSE: To compare the vertebral height restoration
      rate, kyphotic angle, and clinical results of patients who underwent kyphoplasty
      according to the degree of anterior vertebral height loss. In addition, to
      determine the feasibility and effects of kyphoplasty on severely collapsed
      osteoporotic vertebral fractures. STUDY DESIGN/SETTING: A retrospective study.
      PATIENT SAMPLE: A total of 129 patients (145 vertebrae) who underwent kyphoplasty
      for osteoporotic painful vertebral fracture and followed up for more than 1 year
      between September 2005 and August 2012 were recruited for the analysis. OUTCOME
      MEASURES: The patients' kyphotic angle, anterior vertebral height, and anterior
      vertebral height restoration ratio 1 year after surgery were compared. Pre- and
      postoperative pain around the fractured vertebra and the radiological and
      clinical results according to bone mineral density (BMD) were also compared.
      METHODS: Patients were divided into three groups for comparison, according to
      radiographic findings. Patients with an anterior height compression ratio more
      than 70% at the time of fracture comprised Group I, patients with a compression
      ratio of 50-70% comprised Group II, and those with a compression ratio of 30-50%
      comprised Group III. RESULTS: Group I showed a greater extent of anterior height
      restoration immediately after surgery compared with the other groups, which
      noticeably decreased over time. All three groups showed significant restoration
      of the anterior vertebral height between pre- and postoperative values. The
      anterior vertebral height 1 year after surgery did not differ between Group I and
      Group II but was significantly higher in Group III. There was no correlation
      between the BMD and restoration or decrease of anterior vertebral height over
      time. Pain around the fractured vertebra significantly decreased in all groups
      immediately and 1 year after surgery compared with preoperative levels, although
      the pain level 1 year after surgery did not differ significantly between the
      groups. CONCLUSIONS: In patients with an anterior vertebral compression ratio
      more than 70% because of osteoporotic vertebral fracture, although the anterior
      height and kyphotic angle were significantly lower than those of patients with an
      anterior vertebral compression ratio of 30% to 50%, kyphoplasty significantly
      improved the degree of pain, restored the anterior vertebral height, and
      maintained the kyphotic angle. Therefore, kyphoplasty can be a useful approach in
      patients with an anterior vertebral compression ratio more than 70%.

PMID- 24462537
TI  - Incidence and risk factors for first-time incident low back pain: a systematic
      review and meta-analysis.
AB  - BACKGROUND CONTEXT: Great effort has been made toward limiting low back pain
      (LBP). Recent focus has included factors involved with secondary and tertiary
      prevention, with less attention given to primary prevention. PURPOSE: This review
      provided a current estimate of the incidence of LBP and risk factors associated
      with either first-time LBP or transition to LBP from a baseline of a pain-free
      state. STUDY DESIGN: A systematic review and meta-analyses were performed
      according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines. PATIENT SAMPLE: Studies included subjects aged 18 years or
      older, from longitudinal, observational, cohort designs that included baseline
      risk factors to an outcome of either first-time LBP or transition to LBP from a
      baseline of a pain-free state. OUTCOME MEASURES: Risk factors and incidence rates
      were reported using descriptive analysis and the PRISMA guidelines. METHODS:
      Electronic search strategies in PubMed, CINAHL/SPORTDiscus, and Cochrane Central
      Register of Controlled Trials were combined with a hand search to identify
      articles for inclusion. Studies were classified based on the population studied
      (community vs. occupational based) and type of LBP outcome (first ever vs.
      transition from a baseline pain-free state). RESULTS: A total of 41 studies were
      included for review. Meta-analytical incidence rates for first-time LBP and
      transition to pain from a pain-free state were similar (~25%), regardless of
      community or occupational populations. Risk factors for first-time LBP or
      transition to LBP from a baseline of a pain-free state were psychosocial and
      physically related. No consistent risk factor emerged as predictive of first-time
      LBP, although prior LBP was a consistent predictor of future incident LBP.
      Significant heterogeneity was found across studies in most models, which limits
      these findings. CONCLUSIONS: The results of this study suggest that incidence of
      LBP is similar in community and occupational settings regardless of LBP
      definition. There were multiple diverse physical and psychosocial risk factors
      for first-time LBP. A history of LBP was the most consistent risk factor for
      transition to LBP from a baseline of a pain-free state.

PMID- 24462538
TI  - Internal jugular vein stenosis is common in patients presenting with neurogenic
      thoracic outlet syndrome.
AB  - Previous magnetic resonance imaging studies have shown abnormalities of the
      internal jugular veins in patients with thoracic outlet syndrome (TOS), but this
      finding has largely been ignored. We, thus, prospectively performed diagnostic
      brachiocephalic venograms in all patients with diagnosed neurogenic TOS from
      April 2008 to December 2011 (mean age, 42.6; r, 16-68; 77.8% women and 22.2%
      men). Stenosis of the left internal jugular vein, left subclavian vein, right
      internal jugular vein, and right subclavian vein were assessed, and significant
      stenoses of these vessels were seen in 63.49%, 65.08%, 60.32%, and 68.25% of
      patients, respectively. Internal jugular vein stenosis was not present in 23.81%,
      present unilaterally in 28.57%, and present bilaterally in 47.62% of patients.
      Subclavian vein stenosis was not present in 17.46%, present unilaterally in
      28.57%, and present bilaterally in 53.97% of patients. Phi coefficients of
      correlation were 0.067 between left internal jugular vein and left subclavian
      vein stenoses, 0.061 between right internal jugular vein and right subclavian
      vein stenoses, and 0 between any internal jugular vein and any subclavian vein
      stenoses, indicating there is no correlation between jugular vein stenosis and
      subclavian vein stenosis in these patients. We conclude that right and left
      internal jugular vein stenosis is common in patients with neurogenic TOS
      symptoms. Treatment of internal jugular vein stenosis could potentially benefit
      these patients, and the implications of these findings warrant further study. 

PMID- 24462539
TI  - Remaining or residual first ribs are the cause of recurrent thoracic outlet
      syndrome.
AB  - BACKGROUND: Surgical intervention for neurogenic thoracic outlet syndrome (NTOS)
      is not always successful. Treatment plans can be difficult in patients presenting
      with recurrent symptoms. The purpose of this study was to evaluate outcomes of
      this patient subset, who underwent operative intervention to remove a remaining
      or residual first rib because of recurrent thoracic outlet syndrome (TOS)-related
      symptoms. METHODS: Data on 15 patients who presented with previous scalenectomy,
      brachial plexus lysis, or first rib resection and scalenectomy (FRRS) with
      residual rib present on chest radiograph from 2004 to 2012 were retrospectively
      reviewed from a prospectively maintained database, with approval from the
      Institutional Review Board of Johns Hopkins Hospital. Patients were classified as
      having a remaining first rib if they presented with recurrent NTOS symptoms, had
      previously undergone scalenectomy and/or brachial plexus lysis alone to
      decompress the thoracic outlet, and exhibited an intact first rib on chest X-ray,
      whereas patients were classified as having a remnant rib if they presented with
      recurrent symptoms of NTOS, had previously undergone a first rib resection at
      another institution, and exhibited an anterior or posterior first rib on chest X
      ray. Demographic and clinical characteristics along with postoperative outcomes
      were evaluated. RESULTS: Different precipitating events reaggravated symptoms in
      12 patients. Events included car accidents (n = 4), work-related repetitive
      movements (n = 5), lifting heavy objects (n = 2), and repetitive injury (n = 1).
      Group 1: Previous scalenectomy (n = 2), brachial plexus lysis alone (n = 2), or
      both (n = 3). Seven patients (2 men and 5 women; mean age 34 [25-53]) presented
      with NTOS symptoms due to a remaining first rib at an average of 24 months
      (range: 2-68) after their initial operation at another institution. All underwent
      transaxillary first rib resection, residual scalene resection, and lysis of scar
      tissue. Perioperative complications included 3 pneumothoraces without any artery,
      vein, or brachial plexus injury. Average follow-up was 17 months (range: 1-79),
      and all the patients improved in the postoperative period. Group 2: Residual rib
      (n = 8). Eight patients (2 men and 6 women; mean age 39 [24-58]) presented with a
      residual first rib at an average of 44 months (range: 12-107) after their initial
      operation at another institution. Six patients had undergone prior
      supraclavicular FRRS, 1 had undergone previous transaxillary FRRS, and 1 had
      undergone FRRS via an anterior chest approach. Of the 8 patients, 7 presented
      with neurogenic symptoms alone, and 1 presented with recurrent venous thrombosis
      in addition. A residual rib was present in all the 8 patients, as seen by a chest
      radiograph. A transaxillary approach was used to resect the residual first rib,
      anterior scalene muscle remnant, and scar tissue in 7 patients, and a
      supraclavicular approach was used in 1 patient. Perioperative complications
      included 4 pneumothoraces without any artery, vein, or brachial plexus injury.
      Average follow-up was 13 months (range: 1-64), and all the patients improved in
      the postoperative period. CONCLUSIONS: Patients who present with recurrent
      symptoms of TOS need to be evaluated for remaining or residual first ribs.
      Operative intervention to remove the remaining or residual first rib in this
      patient subset is beneficial and can be performed without significant morbidity.
      Patients undergoing procedures for TOS support our procedure of complete first
      rib removal at the time of the initial operation to prevent recurrence of
      symptoms.

PMID- 24462540
TI  - Diagnostic accuracy of physician and self-referred patients for thoracic outlet
      syndrome is excellent.
AB  - BACKGROUND: The purpose of this study was to categorize patients referred to a
      specialized thoracic outlet syndrome (TOS) practice to determine the diagnostic
      accuracy of those who are physician and self-referred. METHODS: Demographic and
      clinical data on all patients who were referred for TOS between 2006 and 2010
      were retrospectively reviewed from a prospectively maintained institutional
      review board-approved database and patient records. RESULTS: Between 2006 and
      2010, 621 patients were referred for TOS (433 women and 188 men; mean age 39
      years [range 10-87]). Five hundred seventy-one patients (92%) were diagnosed with
      TOS, with 421 (74%) neurogenic, 126 (22%) venous, and 24 (4%) arterial TOS cases.
      Of the 525 physician referrals, 478 (91%) had TOS, and of the 93 self-referrals,
      90 (97%) had TOS. The 421 patients with neurogenic TOS (NTOS, 304 women and 117
      men) had symptoms on average for 56 months (range 1-516). Two hundred seventy-one
      patients (64%) were initially treated with TOS-specific physical therapy (PT),
      and 100 (37%) improved. One hundred seventy-eight patients (42%) underwent a
      lidocaine block, and 145 patients (81%) had a positive block. Seventy-four
      patients (18%) underwent Botox injections 44 (60%) of which were positive and the
      average number of Botox injections was 1.3. One hundred forty patients (33%)
      underwent transaxillary first rib resection and scalenectomy (FRRS), and 128
      patients (91%) improved. Of patients undergoing FRRS, 92 (66%) had a lidocaine
      block, 82 (89%) of which were positive. Of patients with a positive lidocaine
      block, 74 (90%) improved after FRRS. Of patients undergoing FRRS, 31 (22%)
      underwent Botox injections, 15 (48%) of which were positive. Of patients with a
      positive Botox block, 14 (93%) improved after FRRS. Average length of time
      between initial visit and operation was 6.4 months (range 2 weeks to 34 months),
      and average follow-up time was 13 months (range 1 week to 49 months).
      CONCLUSIONS: 1) Both referring physicians and patients are very accurate in their
      preliminary diagnosis of TOS (neurogenic, venous, or arterial TOS). 2) In a
      specialized TOS practice, two-thirds of patients are sent to TOS-specific PT and
      one-third improve from this treatment alone. 3) One-third of patients referred
      for NTOS eventually undergo FRRS with a 91% success rate.

PMID- 24462541
TI  - A study on cryoprotectant solution suitable for vitrification of rat two-cell
      stage embryos.
AB  - The present study was performed to develop a suitable cryoprotectant solution for
      cryopreservation of rat two-cell stage embryos. First, we examined the cell
      permeability of several cryoprotectants; propylene glycol had the fastest
      permeability compared to dimethyl sulfoxide, ethylene glycol, and glycerol.
      Embryos were then exposed to a solution containing propylene glycol to evaluate
      its effects on fetal development. As the development was similar to that of fresh
      embryos, P10 (10% v/v propylene glycol in PB1) was used as a pretreatment
      solution. Next, the effects of the vitrification solution components (sucrose,
      propylene glycol, ethylene glycol, and Percoll) were examined by observing the
      vitrification status; 10% v/v propylene glycol, 30% v/v ethylene glycol, 0.3 mol
      sucrose, and 20% v/v Percoll in PB1 (PEPeS) was the minimum essential
      concentration for effective vitrification without the formation of ice crystals
      or freeze fractures. A new vitrification method using P10 and PEPeS was tested
      using rat embryos. The survival rate of vitrified embryos after exposure to P10
      for 120, 300, or 600 s ranged from 95.9% to 98.3%. The fetal developmental rate
      ranged from 57.7% to 65.2%, which was not significantly different from that of
      fresh embryos. The experimental results indicated that vitrification using a
      combination of P10 and PEPeS was suitable for cryopreservation of rat early stage
      embryos.

PMID- 24462542
TI  - Development of a luciferase-based system for the detection of ZnT8
      autoantibodies.
AB  - Appearance of autoantibodies represents the first detectable sign of autoimmune
      destruction of beta cells in type 1 diabetes (T1D). In addition, autoantibody
      levels represent an important predictive marker regarding the development of an
      autoimmune process. Recently, the zinc transporter (ZnT8) protein was identified
      as an autoimmune target in T1D; therefore, there is a need for reliable and
      simple methods for detection of ZnT8 autoantibodies. This report describes an
      assay designed to detect anti-ZnT8 autoantibodies in the serum of patients with
      T1D. This was carried out by generating a ZnT8 C-terminal dimer fused to the N
      terminus of the Gaussia princeps luciferase that was overexpressed in insect
      cells using the baculovirus expression system. Recombinant protein was semi
      purified and used as the target antigen in the liquid-phase luciferase
      immunoprecipitation system assay (LIPS), and results were compared to data
      obtained using a commercial ELISA designed to detect ZnT8 autoantibodies in T1D
      patient sera, particularly among adults. LIPS was less effective in detecting
      antibodies in children probably due to the relatively high prevalence of IgM anti
      ZnT8 antibodies in children with T1D. 

PMID- 24462544
TI  - Spinal neuronal NOS activation mediates intrathecal fentanyl preconditioning
      induced remote cardioprotection in rats.
AB  - Fentanyl has been widely used in anesthesia and analgesia, especially for
      cardiovascular surgeries. The aim of the study was to evaluate whether remote
      intrathecal fentanyl preconditioning (RFPC) provides cardioprotection and the
      role of spinal nitric oxide synthase (NOS) system in this effect. Fentanyl
      (0.3MUg/kg) was administered intrathecally during RFPC by 3 cycles of 5-minute
      infusions interspersed with 5-minute infusion free periods. A non-specific nitric
      oxide synthase (NOS) inhibitor NG-nitro l-arginine methyl ester (l-NAME, 30nmol)
      and a selective nNOS inhibitor 7-nitroindazole (7-NI, 100nmol) were administered
      intrathecally 10min before RFPC, and were used to evaluate the involvement of the
      NOS system of the spinal cord. RFPC group markedly reduced the infarct size
      compared with control. However, the cardioprotection of RFPC could be abolished
      by pretreatment with l-NAME and 7-NI. RFPC merely increased the expression of
      nNOS and did not affect iNOS and eNOS expression. l-NAME reversed nNOS expression
      up-regulation induced by RFPC treatment. The present study demonstrated that RFPC
      effectively induced cardioprotection through activating the nNOS in the spinal
      cord. 

PMID- 24462543
TI  - Maternal micronutrient imbalance alters gene expression of BDNF, NGF, TrkB and
      CREB in the offspring brain at an adult age.
AB  - Micronutrients like folate, vitamin B12, and fatty acids which are interlinked in
      the one carbon cycle play a vital role in mediating epigenetic processes leading
      to an increased risk for neurodevelopmental disorders in the offspring. Our
      earlier study demonstrates that a micronutrient imbalanced diet adversely affects
      docosahexaenoic acid (DHA) and protein levels of neurotrophins like brain-derived
      neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain and
      cognition in the offspring by 3 months of age. In this study we attempt to
      analyze if these effects are a consequence of a change in gene expression of
      these molecules. Further, we also examined the effect of either a postnatal
      control diet or a prenatal omega-3 fatty acid supplementation on gene expression
      in the cortex of the offspring. Pregnant rats were divided into control and five
      treatment groups at two levels of folic acid (normal and excess folate) in the
      presence and absence of vitamin B12. Omega-3 fatty acid (eicosapentaenoic acid -
      EPA+DHA) supplementation was given to vitamin B12 deficient groups. Following
      delivery, 8 dams from each group were shifted to control diet and remaining
      continued on the same treatment diet. Our results demonstrate that the imbalanced
      diet caused a marked reduction in the mRNA levels of BDNF, NGF, TrkB, and cAMP
      response element-binding protein (CREB). Prenatal omega-3 fatty acid
      supplementation to the maternal imbalanced diet was able to normalize the mRNA
      levels of all the above genes. This study demonstrates that a maternal diet
      imbalanced in micronutrients (folic acid, vitamin B12) influences gene expression
      of neurotrophins and their signalling molecules and thereby adversely affects the
      brain of the offspring. 

PMID- 24462547
TI  - Pancreatectomy for metastatic disease: a systematic review.
AB  - AIM: Tumours rarely metastasise to the pancreas. While surgical resection of such
      metastases is believed to confer a survival benefit, there is limited data to
      support such management. We present a systematic review of case series of
      pancreatic metastasectomy and analysis of survival outcomes. METHODS: A
      literature search was performed using the PubMed and Cochrane databases and the
      reference lists of relevant articles, searching for sizeable case series of
      pancreatic metastasectomy with curative intent. Data extracted included basic
      demographics, histological primary tumour, presentation, operative management,
      complications and survival, while the MINORS index was used to assess study
      quality. RESULTS: 18 studies were found which met our inclusion criteria,
      involving 399 patients. Renal cell carcinoma (RCC) was the commonest malignancy
      metastasising to the pancreas, responsible for 62.6% of cases, followed by
      sarcoma (7.2%) and colorectal carcinoma (6.2%). While survival data was not
      uniformly reported, the median survival post-metastasectomy was 50.2 months, with
      a one-year survival of 86.81% and five-year survival of 50.02%. Median survival
      for RCC was 71.7 months with 70.4% five-year survival. Median survival was
      similar in patients with synchronous and metachronous pancreatic metastases, but
      patients with additional extrapancreatic metastases had a significantly shorter
      survival than patients with isolated pancreatic metastases (26 versus 45 months).
      Study quality was poor, with a median MINORS score of 10/16. CONCLUSIONS: Within
      the limitations of a review of non-randomised case series, it would appear that
      pancreatic metastasectomy confers a survival benefit in selected patients. Better
      evidence is required, but may prove difficult to acquire.

PMID- 24462548
TI  - Follow-up after cystectomy: regularly scheduled, risk adjusted, or symptom
      guided? Patterns of recurrence, relapse presentation, and survival after
      cystectomy.
AB  - AIMS: To evaluate the efficacy of follow-up based on the patterns of recurrence,
      relapse presentation and survival after cystectomy, and to define a risk adjusted
      follow-up schedule. PATIENTS AND METHODS: The records of 343 patients with
      regular follow-up after cystectomy were reviewed for primary site of recurrence,
      accompanying symptoms, means of recurrence diagnosis, and clinicopathological
      factors. Based on Cox proportional hazard models, and the results of imaging
      studies low and high risk groups are identified and a risk adjusted follow-up
      protocol is proposed. RESULTS: The risk of a recurrence was related to increasing
      pT, tumour positive lymph nodes, tumour positive surgical margins, and pre
      operative dilatation of the upper urinary tract, and low and high risk groups
      were defined consequently. 84% of all recurrences occurred within 2 years, with
      only one recurrence beyond 2 years in the low risk group. Although the minority
      of all patients (34%) is asymptomatic at time of recurrence, symptomatic
      recurrences were adversely associated with survival. CT-scans and chest X-rays
      accounted for 90% of the diagnostic tools to detect a recurrence in patients
      without symptoms. CONCLUSIONS: Asymptomatic patients may benefit from early
      treatment after disease recurrence. A risk adjusted follow-up strategy based on
      stage of disease and additional clinicopathological factors can dichotomise
      patients at high and low risk for recurrence. The small benefit in survival after
      early detection has to be confirmed in future studies, and weighed against the
      available treatment options of recurrences and their subsequent costs.

PMID- 24462549
TI  - Has PET/CT a role in the characterization of indeterminate lung lesions on
      staging CT in colorectal cancer? A prospective study.
AB  - PURPOSE: CT has been found superior to chest x-ray to detect lung malignances.
      However, indeterminate lung lesions (ILL) are found in 4-42% by using CT in
      staging colorectal cancer (CRC) patients. Our aim was to examine the frequency of
      ILL on staging CT and the rate of the ILL being malignant, and to investigate if
      PET/CT was useful in pointing out the malignant cases. METHODS: A prospective
      analysis of 238 consecutive patients operated for CRC followed median 24 months.
      All the patients had a preoperative staging CT. Patients with ILL had a PET/CT
      scan performed 3 months postoperatively and low dose chest CT performed 6, 12, 18
      and 24 months postoperatively. RESULTS: Twenty percent of the patients had ILL.
      Four of these patients (8.5%) had lung metastases detected median 9 months
      postoperatively, while 2 (4.3%) had other lung malignancies. One patient had TB.
      In patients with normal staging chest CT 10 of the 185 patients (5.4%) developed
      lung metastases detected median 16 months postoperatively. This was significantly
      later than in patients with ILL (p < 0.001), but with regard to the number of
      patients developing lung metastases no significant difference was found between
      the groups (p = 0.12). CONCLUSIONS: Even though a relative low number of ILL turn
      out to be malignant it seems advisable to use PET/CT scan in the follow-up to
      detect lung metastases as early as possible to better the prognosis. For the same
      reason all CRC patients should have chest CT included in their follow-up 6-12
      months postoperatively.

PMID- 24462551
TI  - Study of the biologic behavior of odontogenic keratocyst and orthokeratinaized
      odontogenic cyst using TGF-alpha and P53 markers.
AB  - Odontogenic keratocyst (OKC) is an aggressive cyst, and its recurrence rate is
      higher than that of other odontogenic cysts. Orthokeratinized odontogenic cyst
      (OOC) is less aggressive than OKC, but bears the probability of carcinomatous
      changes. In this study, we evaluated the expression and intensity of P53 and TGF
      alpha in order to compare the biologic behavior or probable carcinomatous changes
      of these two cysts. In this cross-sectional study, 15 OKC and 15 OOC were stained
      immunohistochemically for P53 and TGF-alpha using the Novolink polymer method.
      Then, all slides were examined by an optical microscope with 400* magnification,
      and the stained cells in the basal and parabasal layers were counted. Finally,
      the results were analyzed by the Mann-Whitney and Wilcoxon tests (P-value<0.05).
      The difference between the expression of P53 and TGF alpha in the basal layer of
      OKC and OOC was not statistically significant (P-value>0.05), but the expression
      of P53 and TGF-alpha in the parabasal layer in OKC was statistically higher
      compared to OOC (P<0.05). Considering the known role of P53 and TGF-alpha in
      malignant changes and the higher expression of P53 and TGF-alpha in OKC compared
      to those in OOC, the probability of carcinomatous changes was higher in OKC than
      in OOC. 

PMID- 24462550
TI  - Predictive factors of transarterial chemoembolisation toxicity in unresectable
      hepatocellular carcinoma.
AB  - BACKGROUND: Transarterial chemoembolisation (TACE) is an effective treatment for
      unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity. AIM:
      To identify predictive factors of severe TACE-related toxicity in patients with
      unresectable HCC. METHODS: All HCC patients who underwent TACE at the Dijon
      University Hospital between 2008 and 2011 were included in this retrospective
      study. Severe TACE-related toxicity was defined as the occurrence of any adverse
      event grade >= 4, or any adverse event that caused a prolongation of
      hospitalisation of >8 days, or any additional hospitalisation within 1 month
      after TACE. Factors predicting toxicity were identified using a logistic
      regression model. The robustness of the final model was confirmed using
      bootstrapping (500 replications). RESULTS: 124 patients were included, median age
      was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related
      toxicity. Factors that independently predicted severe TACE-related toxicity in
      multivariate analysis were total tumour size (OR, 1.15 cm(-1); 95%CI, 1.04-1.26;
      p=0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01-1.21;
      p=0.04). The results were confirmed by bootstrapping. CONCLUSIONS: Total tumour
      size and high serum AST levels were predictive factors of severe TACE-related
      toxicity in this hospital-based series of patients with unresectable HCC.

PMID- 24462552
TI  - Differential expression and localization of neuropeptide Y peptide in pancreatic
      islet of diabetic and high fat fed rats.
AB  - Neuropeptide Y (NPY) inhibits insulin secretion. Increased numbers of pancreatic
      islet cells expressing NPY have been observed in type 1 diabetic rats. To
      understand the functional significance of NPY expression in islet cells, we
      investigated the effects of high fat feeding and diabetic conditions on the
      expression and location of NPY expressing cells in normal and diabetic rats.
      Twenty rats were maintained on either normal chow (ND) or a high fat dietary
      regimen (HFD) for 4 weeks. In half of each group, type 1 or type 2 diabetes
      (groups T1DM and T2DM, respectively) was induced by injection of streptozotocin.
      At 8 weeks rats were euthanized and the pancreases were processed for
      immunofluorescence labeling (NPY/insulin, NPY/glucagon, NPY/somatostatin, and
      NPY/pancreatic polypeptide). Compared with the ND group, HFD rats had
      significantly fewer alpha cells, but beta cells were similar, while T1DM and T2DM
      rats showed significant increases in the proportions of alpha, delta, and PP
      cells. Robust increases in NPY-positive islet cells were found in the HFD, T1DM,
      and T2DM rats compared with ND controls. In ND rats, 99.7% of the NPY-positive
      cells were PP cells. However, high fat feeding and diabetes resulted in
      significant increases in NPY-positive delta cells, with concomitant decreases in
      NPY-positive PP cells. In summary, high-fat feeding and diabetes resulted in
      changes in the hormonal composition of pancreatic islet and increased number of
      NPY-expressing islet cells. Under diabetic conditions NPY expression switched
      from predominantly a characteristic of PP cells to predominantly that of delta
      cells. This may be a factor in reduced pancreatic hormone secretion during
      diabetes. 

PMID- 24462553
TI  - Comparative analysis of melanoma deregulated miRNAs in the medaka and Xiphophorus
      pigment cell cancer models.
AB  - Malignant melanoma is the most aggressive and deadly form of skin cancer, with an
      almost 100% development of resistance to current therapeutic approaches at
      progression stages. The incidence of melanoma is steadily increasing worldwide.
      Although many details leading to the development of malignant melanoma are known,
      the complex process of melanomagenesis is poorly understood. MicroRNAs (miRNAs)
      are a class of small noncoding-RNAs of ~22nt length that regulate gene expression
      at the post-transcriptional level. It is now well established that deregulated
      miRNA expression is seen in many cancers including melanoma. To further study the
      miRNA functions in melanoma formation and progression we use a transgenic
      melanoma model in Japanese ricefish (medaka; Oryzias latipes) and the natural
      Xiphophorus melanoma model. In these fishes, dependent on the genetic background
      various histo- and patho-types of tumors appear, comparable to human melanoma
      types. We have studied expression profiles of ten known human melanoma-associated
      miRNAs and their respective target gene expression in the fish melanoma models.
      We show that miRNAs of the miR-17-92 cluster (miR-20a2, miR-92a1, miR-17 and miR
      18a), miR-126, miR-182, miR-210 and miR-214 are upregulated and their respective
      target genes (RUNX1, HIF1A, TGFBR2, THBS1 and JAK2) are down-regulated in
      melanoma. MicroRNA-125b is down-regulated and the target genes (ERBB3a and
      ERBB3b) are upregulated in fish melanomas. Results provide clear evidence that
      the fish melanoma-associated miRNAs and respective target genes are deregulated
      generally like in human melanoma. Our results confirm the value of fish; such as
      medaka and Xiphophorus as good model systems to identify and decipher molecular
      mechanisms associated with malignant melanoma.

PMID- 24462554
TI  - Prognostic value of the pre-transplant diastolic pulmonary artery pressure-to
      pulmonary capillary wedge pressure gradient in cardiac transplant recipients with
      pulmonary hypertension.
AB  - BACKGROUND: Although the transpulmonary gradient (TPG) and pulmonary vascular
      resistance (PVR) are commonly used to differentiate heart failure patients with
      pulmonary vascular disease from those with passive pulmonary hypertension (PH),
      elevations in TPG and PVR may not always reflect pre-capillary PH. Recently, it
      has been suggested an elevated diastolic pulmonary artery pressure-to-pulmonary
      capillary wedge pressure gradient (DPG) may be a better indicator of pulmonary
      vascular remodeling, and therefore, may be of added prognostic value in patients
      with PH being considered for cardiac transplantation. METHODS: Using the United
      Network for Organ Sharing (UNOS) database, we retrospectively reviewed all
      primary adult (age > 17 years) orthotropic heart transplant recipients between
      1998 and 2011. All patients with available pre-transplant hemodynamic data and PH
      (mean pulmonary artery pressure >= 25 mm Hg) were included (n = 16,811). We
      assessed the prognostic value of DPG on post-transplant survival in patients with
      PH and an elevated TPG and PVR. RESULTS: In patients with PH and a TPG > 12 mm Hg
      (n = 5,827), there was no difference in survival at up to 5 years post-transplant
      between high DPG (defined as >=3, >=5, >=7, or >=10 mm Hg) and low DPG (<3, <5,
      <7, or <10 mm Hg) groups. Similarly, there was no difference in survival between
      high and low DPG groups in those with a PVR > 3 Wood units (n = 6,270). Defining
      an elevated TPG as > 15 mm Hg (n = 3,065) or an elevated PVR > 5 (n = 1,783)
      yielded similar results. CONCLUSIONS: This large analysis investigating the
      prognostic value of DPG found an elevated DPG had no effect on post-transplant
      survival in patients with PH and an elevated TPG and PVR.

PMID- 24462555
TI  - One generation's "junk" is another's treasure: the emerging role of microRNAs as
      therapeutic targets.

PMID- 24462556
TI  - Abnormal nutrition impacts waitlist mortality in infants awaiting heart
      transplantation.

PMID- 24462557
TI  - Scientific progress in heart and lung failure, mechanical circulatory support,
      and transplantation: highlights from the Journal of Heart and Lung
      Transplantation.
AB  - At the Thirty-third Annual Meeting and Scientific Sessions of the International
      Society of Heart and Lung Transplantation (Montreal, Quebec, Canada), a joint
      session between the Junior Faculty Council members and the editorial consultants
      of the Journal of Heart and Lung Transplantation took place to summarize recently
      published impacting publications in the Journal. The topics reviewed were
      mechanical circulatory support, heart transplantation, lung transplantation,
      pulmonary hypertension and pediatrics. The cooperative presentations has been
      formulated into the present report. 

PMID- 24462558
TI  - Safety of discontinuation of anti-coagulation in patients with continuous-flow
      left ventricular assist devices.

PMID- 24462559
TI  - Mortality and morbidity after retransplantation after primary heart transplant in
      childhood: an analysis from the registry of the International Society for Heart
      and Lung Transplantation.
AB  - BACKGROUND: Retransplantation for graft failure in the pediatric population is
      rare with reports of decreased survival compared with primary transplantation.
      Little is known about the risk factors for retransplantation or death after
      retransplantation; in addition, there is a paucity of data in the literature on
      transplant-related morbidities in this patient population. The purpose of this
      analysis of the registry of the International Society of Heart and Lung
      Transplant (ISHLT) was to describe outcomes after retransplantation as compared
      with primary transplantation, including identifying risk factors leading to
      retransplantation and both transplant-related morbidities and mortality after
      retransplantation. METHODS: Data from 1998 to 2010 were used to identify all
      patients whose primary transplantation was performed at <18 years of age. Of the
      9,966 transplants reviewed, 9,248 primary transplants and 602 retransplants were
      analyzed. RESULTS: The median age for retransplantation was 14 (range 1 to 26)
      years, with the most common indication being allograft vasculopathy (58.5%).
      After retransplantation, early time-related risk of mortality was similar to that
      after primary transplantation (HR 1.07 [0.92 to 1.25], p = 0.40), but both late
      phase time-related risk of mortality (HR 1.67 [1.40 to 1.99], p < 0.001) and
      requirement of an additional graft (HR 1.69 [1.18 to 2.43], p = 0.004) were
      higher. Long-term morbidities were significantly more common after
      retransplantation than with primary transplantation. These included allograft
      vasculopathy (HR 2.8 [2.37 to 3.38], p < 0.001), late rejection (HR 2.0 [1.65 to
      2.40], p < 0.001) and late renal dysfunction (HR 2.6 [2.18 to 3.12], p < 0.001),
      but not cancer (HR 1.16 [0.74 to 1.82], p = 0.52). Numerous patient-, donor- and
      transplant-related risk factors were identified that increased both the risk of
      mortality and transplant-related morbidities after retransplantation.
      CONCLUSIONS: Retransplantation after primary transplant in the pediatric age
      group, although feasible with similar early survival, is associated with
      decreased long-term survival and an increase in transplant-related morbidities.
      The results of this study highlight the ongoing challenges of managing patients
      after retransplant and also suggest some modifiable risk factors, for both the
      donor and recipient, which may improve survival and decrease the burden of
      morbidities.

PMID- 24462560
TI  - Warm-up with a weighted vest improves running performance via leg stiffness and
      running economy.
AB  - OBJECTIVES: To determine the effects of "strides" with a weighted-vest during a
      warm-up on endurance performance and its potential neuromuscular and metabolic
      mediators. A bout of resistance exercise can enhance subsequent high-intensity
      performance, but little is known about such priming exercise for endurance
      performance. DESIGN: A crossover with 5-7 days between an experimental and
      control trial was performed by 11 well-trained distance runners. METHODS: Each
      trial was preceded by a warm-up consisting of a 10-min self-paced jog, a 5-min
      submaximal run to determine running economy, and six 10-s strides with or without
      a weighted-vest (20% of body mass). After a 10-min recovery period, runners
      performed a series of jumps to determine leg stiffness and other neuromuscular
      characteristics, another 5-min submaximal run, and an incremental treadmill test
      to determine peak running speed. Clinical and non-clinical forms of magnitude
      based inference were used to assess outcomes. Correlations and linear regression
      were used to assess relationships between performance and underlying measures.
      RESULTS: The weighted-vest condition resulted in a very-large enhancement of peak
      running speed (2.9%; 90% confidence limits +/-0.8%), a moderate increase in leg
      stiffness (20.4%; +/-4.2%) and a large improvement in running economy (6.0%; +/
      1.6%); there were also small-moderate clear reductions in cardiorespiratory
      measures. Relationships between change scores showed that changes in leg
      stiffness could explain all the improvements in performance and economy.
      CONCLUSIONS: Strides with a weighted-vest have a priming effect on leg stiffness
      and running economy. It is postulated the associated major effect on peak
      treadmill running speed will translate into enhancement of competitive endurance
      performance.

PMID- 24462562
TI  - Analysis of miRNA expression profiling in human macrophages responding to
      Mycobacterium infection: induction of the immune regulator miR-146a.
AB  - OBJECTIVES: The regulatory mechanism of microRNA (miRNA) within macrophage
      innative response to Mycobacterium tuberculosis infection is not clear yet.
      METHODS: The expression profile of cellular miRNAs during Mycobacterium bovis BCG
      infection was analyzed by using microarray. The expression of miR-146a was
      evaluated in alveolar macrophages (AMs) of bronchoalveolar lavage solution from
      pulmonary tuberculosis (PTB) patients and healthy volunteers respectively.
      Inhibitor experiment and promoter analysis were used to investigate the pathway
      involved in the induction of miR-146a. Examination of miR-146a function in
      macrophages was performed by overexpression and inhibition of miR-146a. RESULTS:
      Among the altered miRNAs, 10 were downregulated whereas 8 were upregulated in M.
      bovis BCG-infected macrophage. MiR-146a was high expressed in cultured macrophage
      respond to M. bovis BCG but decreased in AMs of PTB patients, and stated a
      negative correlation with degree of smear-positive. Nuclear factor-kappaB pathway
      was required for the induction of miR-146a. Overexpression of miR-146a results in
      significant reduction of PTGS2 and enhanced the killing ability of THP-1 cells to
      intracellular M. bovis BCG, and miR-146a negatively regulated TNF-alpha release
      in feedback manner. CONCLUSIONS: Our findings suggest an important role of miR
      146a in M. bovis BCG infection that helps to fine-tune the inflammation response
      of MTB infection.

PMID- 24462563
TI  - Serum galactomannan antigen test for the diagnosis of chronic pulmonary
      aspergillosis.
AB  - BACKGROUND: A serum galactomannan (GM) antigen test has been widely used to
      diagnose invasive pulmonary aspergillosis. However, there are limited data on the
      use of the serum GM antigen test for the serologic diagnosis of chronic pulmonary
      aspergillosis (CPA). METHODS: Data were collected from all consecutive patients
      with a clinical suspicion of CPA who underwent a serum GM antigen test. RESULTS:
      In total, 334 patients who were suspected to have CPA were eligible for this
      study and 168 (50%) patients were finally diagnosed with CPA. The serum GM
      antigen test was positive in 38 (23%) patients with CPA and in 25 (15%) patients
      without CPA. The sensitivity of the serum GM antigen test was 23% (95% confidence
      interval [CI], 17-30%), and its specificity was 85% (95% CI, 79-90%), with
      positive and negative predictive values of 60% (95% CI, 47-72%) and 52% (95% CI,
      46-58%), respectively. The accuracy of the test was 54%. The area under the
      receiver operating characteristic curve was 0.538 (95% CI, 0.496-0.580).
      CONCLUSION: The serum GM antigen test could not be used for the serologic
      diagnosis of CPA.

PMID- 24462564
TI  - Statin drugs markedly inhibit testosterone production by rat Leydig cells in
      vitro: implications for men.
AB  - Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3
      methylglutaryl-Coenzyme-A reductase. Statins are known to inhibit sterol
      production in the testis, but effect of statins on testosterone production has
      not been studied critically in vitro and clinical data are controversial. We
      measured 18-h testosterone production in vitro, using highly purified rat Leydig
      cells exposed to atorvastatin, mevastatin, or simvastatin and also determined if
      statin-induced inhibition of testosterone production could be bypassed with
      substrate distal to cholesterol. Statins had no effect on testosterone production
      during culture without LH. However, with 10ng/mL LH, testosterone production was
      >=12-fold higher and markedly inhibited (-40%) by >=0.3MUM statin. Leydig cells
      provided sub-saturating pregnenolone or progesterone to bypass the site of statin
      action, maintained LH-stimulated testosterone production at or above amounts
      observed with LH stimulation and no statin. Pregnenolone resulted in greater
      testosterone production, but LH responsiveness was lost. With progesterone, LH
      responsiveness was maintained. 

PMID- 24462565
TI  - Antiviral innate immunity: editorial overview.

PMID- 24462561
TI  - Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from
      Latin America and Caribbean countries.
AB  - OBJECTIVES: To evaluate the incidence of and risk factors for hypertensive
      disorders in a cohort of HIV-infected pregnant women. METHODS: Hypertensive
      disorders (HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced
      hypertension, and risk factors were evaluated in a cohort of HIV-infected
      pregnant women from Latin America and the Caribbean enrolled between 2002 and
      2009. Only pregnant women enrolled for the first time in the study and delivered
      at >=20 weeks gestation were analyzed. RESULTS: HD were diagnosed in 73 (4.8%,
      95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly
      increased among women with a gestational age-adjusted body mass index (gBMI) >=25
      kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) >=11 g/dL at delivery (OR =
      2.1; 95% CI: 1.2-3.6) and age >=35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was
      increased among women with a gBMI >=25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0) and Hg
      >=11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E
      increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception
      was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9). CONCLUSIONS: HIV-infected
      women, with a previous history of PE/E, a gBMI >=25 kg/m(2), Hg at delivery >=11
      g/dL and in use of HAART before conception are at an increased risk of developing
      PE/E during pregnancy.

PMID- 24462566
TI  - Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down
      syndrome.
AB  - It is known that Alzheimer's disease (AD) presents at an early age in people with
      Down syndrome (DS). The trisomy 21 in DS provides an opportunity to study the
      effect of duplicated genes in AD. APP and BACE2 are 2 genes located in chromosome
      21 and related to AD. We looked into our cohort of 67 DS cases with dementia for
      the effect of BACE2 variants in age of onset of dementia. Of the 83 single
      nucleotide polymorphisms (SNPs), 6 were associated with age of onset and another
      8 SNPs were borderline associated. Our finding also replicated a previous study
      showing association of rs2252576 with AD. 

PMID- 24462567
TI  - A comparison of nonparametric and parametric methods to adjust for baseline
      measures.
AB  - When analyzing the randomized controlled trial, we may employ various statistical
      methods to adjust for baseline measures. Depending on the method chosen to adjust
      for baseline measures, inferential results can vary. We investigate the Type 1
      error and statistical power of tests comparing treatment outcomes based on
      parametric and nonparametic methods. We also explore the increasing levels of
      correlation between baseline and changes from the baseline, with or without
      underlying normality. These methods are illustrated and compared via simulations.

PMID- 24462569
TI  - Quantitative assessments of municipal waste management systems: using different
      indicators to compare and rank programs in New York State.
AB  - The primary objective of waste management technologies and policies in the United
      States is to reduce the harmful environmental impacts of waste, particularly
      those relating to energy consumption and climate change. Performance indicators
      are frequently used to evaluate the environmental quality of municipal waste
      systems, as well as to compare and rank programs relative to each other in terms
      of environmental performance. However, there currently is no consensus on the
      best indicator for performing these environmental evaluations. The purpose of
      this study is to examine the common performance indicators used to assess the
      environmental benefits of municipal waste systems to determine if there is
      agreement between them regarding which system performs best environmentally.
      Focus is placed on how indicator selection influences comparisons between
      municipal waste management programs and subsequent system rankings. The waste
      systems of ten municipalities in the state of New York, USA, were evaluated using
      each common performance indicator and Spearman correlations were calculated to
      see if there was a significant association between system rank orderings.
      Analyses showed that rank orders of waste systems differ substantially when
      different indicators are used. Therefore, comparative system assessments based on
      indicators should be considered carefully, especially those intended to gauge
      environmental quality. Insight was also gained into specific factors which may
      lead to one system achieving higher rankings than another. However, despite the
      insufficiencies of indicators for comparative quality assessments, they do
      provide important information for waste managers and they can assist in
      evaluating internal programmatic performance and progress. To enhance these types
      of assessments, a framework for scoring indicators based on criteria that
      evaluate their utility and value for system evaluations was developed. This
      framework was used to construct an improved model for waste system performance
      assessments. 

PMID- 24462568
TI  - Weight loss intervention for young adults using mobile technology: design and
      rationale of a randomized controlled trial - Cell Phone Intervention for You
      (CITY).
AB  - BACKGROUND: The obesity epidemic has spread to young adults, leading to
      significant public health implications later in adulthood. Intervention in early
      adulthood may be an effective public health strategy for reducing the long-term
      health impact of the epidemic. Few weight loss trials have been conducted in
      young adults. It is unclear what weight loss strategies are beneficial in this
      population. PURPOSE: To describe the design and rationale of the NHLBI-sponsored
      Cell Phone Intervention for You (CITY) study, which is a single center,
      randomized three-arm trial that compares the impact on weight loss of 1) a
      behavioral intervention that is delivered almost entirely via cell phone
      technology (Cell Phone group); and 2) a behavioral intervention delivered mainly
      through monthly personal coaching calls enhanced by self-monitoring via cell
      phone (Personal Coaching group), each compared to 3) a usual care, advice-only
      control condition. METHODS: A total of 365 community-dwelling overweight/obese
      adults aged 18-35 years were randomized to receive one of these three
      interventions for 24 months in parallel group design. Study personnel assessing
      outcomes were blinded to group assignment. The primary outcome is weight change
      at 24 [corrected] months. We hypothesize that each active intervention will cause
      more weight loss than the usual care condition. Study completion is anticipated
      in 2014. CONCLUSIONS: If effective, implementation of the CITY interventions
      could mitigate the alarming rates of obesity in young adults through promotion of
      weight loss. ClinicalTrial.gov: NCT01092364.

PMID- 24462570
TI  - Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced
      acute liver toxicity in rats.
AB  - Paracetamol is one of the first rank drugs which cause hepatic damage during drug
      intoxications. Endothelin (ET) which is known as one of the most potent
      vasoactive agent has been shown to contribute in the pathophysiology of various
      diseases. We hypothesized that bosentan, which is a non-selective ET-1 receptor
      antagonist, can prevent liver damage. This study included 49 female rats. Groups;
      I: Healthy group, II: Paracetamol (2 g/kg orally). Groups 3, 4 and 5 received NAC
      140 mg/kg (2 doses), BOS 45 mg/kg and BOS 90 mg/kg orally, respectively. 1 h
      after administration of pretreatment drugs, Groups 3, 4, 5 were given
      paracetamol. VI: received BOS 90 mg/kg. VII: received 140 mg/kg NAC (2 doses).
      According to biochemical results, TNF-alpha, ALT and AST levels were
      statistically increased in the paracetamol group, these parameters were improved
      in the bosentan groups. Paracetamol administration decreased SOD activity, GSH
      level and increased level of MDA in the liver, while bosentan administration
      significantly improved these parameters. In immunohistochemical staining ET-1
      receptor expression was excessively increased in paracetamol group, but not in
      bosentan groups when compared to healthy control. All these results suggest that
      bosentan exerted protective effects against experimentally induced paracetamol
      toxicity in liver.

PMID- 24462571
TI  - A novel synthetic dibenzocyclooctadiene lignan analog XLYF-104-6 attenuates
      lipopolysaccharide-induced inflammatory response in RAW264.7 macrophage cells and
      protects BALB/c mice from sepsis.
AB  - The wide range of inflammation mechanisms under control by NF-kappaB makes this
      pathway as an attractive target for new anti-inflammatory drugs. Herein, we
      showed that a new dibenzocyclooctadiene lignan analog XLYF-104-6, with a chemical
      name of 1,2,3,10,11-pentamethoxydibenzocycloocta-6,7-[c] pyrrole-1,3-dione,
      inhibited lipopolysaccharide (LPS)-induced NF-kappaB activation in RAW264.7 cells
      through preventing IkappaBalpha degradation and p65 nuclear translocation. The
      inhibitory activity of this compound on NF-kappaB activation contributes to the
      reduction of LPS-induced TNF-alpha and IL-6 productions. Notably, XLYF-104-6
      suppressed LPS-induced iNOS expression and NO production in a NF-kappaB
      independent manner, since IKK inhibitor BAY 11-7082 has failed to exert similar
      inhibitory effect on iNOS expression and NO production. In addition, XLFY-104-6
      also exerted anti-inflammatory action in endotoxemic mice by decreasing plasma
      LPS-induced TNF-alpha and IL-1beta levels as well as increasing plasma LPS
      induced IL-10 concentrations. These findings suggest XLYF-104-6 could act as a
      leading compound for developing a potential anti-inflammatory drug. 

PMID- 24462572
TI  - An LED-based UV-B irradiation system for tiny organisms: System description and
      demonstration experiment to determine the hatchability of eggs from four
      Tetranychus spider mite species from Okinawa.
AB  - We developed a computer-based system for controlling the photoperiod and
      irradiance of UV-B and white light from a 5*5 light-emitting diode (LED) matrix
      (100*100mm). In this system, the LED matrix was installed in each of four
      irradiation boxes and controlled by pulse-width modulators so that each box can
      independently emit UV-B and white light at irradiances of up to 1.5 and 4.0Wm(
      2), respectively, or a combination of both light types. We used this system to
      examine the hatchabilities of the eggs of four Tetranychus spider mite species
      (T. urticae, T. kanzawai, T. piercei and T. okinawanus) collected from Okinawa
      Island under UV-B irradiation alone or simultaneous irradiation with white light
      for 12hd(-1) at 25 degrees C. Although no eggs of any species hatched under the
      UV-B irradiation, even when the irradiance was as low as 0.02Wm(-2), the
      hatchabilities increased to >90% under simultaneous irradiation with 4.0Wm(-2)
      white light. At 0.06Wm(-2) UV-B, T. okinawanus eggs hatched (15% hatchability)
      under simultaneous irradiation with white light, whereas other species showed
      hatchabilities <1%. These results suggest that photolyases activated by white
      light may reduce UV-B-induced DNA damage in spider mite eggs and that the greater
      UV-B tolerance of T. okinawanus may explain its dominance on plants in seashore
      environments, which have a higher risk of exposure to reflected UV-B even on the
      undersurface of leaves. Our system will be useful for further examination of
      photophysiological responses of tiny organisms because of its ability to
      precisely control radiation conditions.

PMID- 24462573
TI  - Strength in numbers: large and permanent colonies have higher queen oviposition
      rates in the invasive Argentine ant (Linepithema humile, Mayr).
AB  - Polydomy associated with unicoloniality is a common trait of invasive species. In
      the invasive Argentine ant, colonies are seasonally polydomous. Most follow a
      seasonal fission-fussion pattern: they disperse in the spring and summer and
      aggregate in the fall and winter. However, a small proportion of colonies do not
      migrate; instead, they inhabit permanent nesting sites. These colonies are large
      and highly polydomous. The aim of this study was to (1) search for differences in
      the fecundity of queens between mother colonies (large and permanent) and
      satellite colonies (small and temporal), (2) determine if queens in mother and
      satellite colonies have different diets to clarify if colony size influences
      social organization and queen feeding, and (3) examine if colony location
      relative to the invasion front results in differences in the queen's diet. Our
      results indicate that queens from mother nests are more fertile than queens from
      satellite nests and that colony location does not affect queen oviposition rate.
      Ovarian dissections suggest that differences in ovarian morphology are not
      responsible for the higher queen oviposition rate in mother vs. satellite nests,
      since there were no differences in the number and length of ovarioles in queens
      from the two types of colonies. In contrast, the higher delta(15)N values of
      queens from mother nests imply that greater carnivorous source intake accounts
      for the higher oviposition rates.

PMID- 24462574
TI  - Contribution of the ethics committee of the French society of intensive care
      medicine to a scenario for the implementation of organ donation after Maastricht
      III-type cardiac death in France.
AB  - French law allows organ donation after death due to cardiocirculatory arrest. In
      the Maastricht classification, type III non-heart-beating donors are those who
      experience cardiocirculatory arrest after the withdrawal of life-sustaining
      treatments. French authorities in charge of regulating organ donation (Agence de
      la Biomedecine, ABM) are considering organ collection from Maastricht type III
      donors. We describe a scenario for Maastricht type III organ donation that fully
      complies with the ethical norms governing care to dying patients. That organ
      donation may occur after death should have no impact on the care given to the
      patient and family. The dead-donor rule must be followed scrupulously: the organ
      retrieval procedure must neither cause nor hasten death. The decision to withdraw
      life-sustaining treatments, withdrawal modalities, and care provided to the
      patient and family must adhere strictly to the requirements set forth in patient
      rights legislation (the 2005 Leonetti law in France) and should not be influenced
      in any way by the possibility of organ donation. A major ethical issue regarding
      the family is how best to transition from discussing treatment-withdrawal
      decisions to discussing possible organ retrieval for donation should the patient
      die rapidly after treatment withdrawal. Close cooperation between the healthcare
      team and the organ retrieval team is crucial to minimize the distress of family
      members during this transition. Modalities for implementing Maastricht type III
      organ donation are discussed here, including the best location for withdrawing
      life-sustaining treatments (operating room or intensive care unit). 

PMID- 24462575
TI  - The serine protease inhibitor Ecotin is required for full virulence of
      Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is a Gram negative soil saprophyte that causes the
      disease melioidosis where clinical symptoms can vary from localised infection to
      pneumonia and septic shock. Ecotin is a potent periplasmic serine protease
      inhibitor first identified in Escherichia coli. Ecotin, although present in only
      a small subset of genera, can inhibit a broad range of serine proteases including
      those typically associated with the innate immune system such as neutrophil
      elastase and cathepsin G. An Ecotin orthologue identified in B. pseudomallei was
      recombinantly expressed and found to inhibit elastase. To study the role of
      Ecotin in B. pseudomallei virulence an in-frame unmarked deletion mutant was
      created. Infection of a murine macrophages-like cell line revealed Ecotin was
      necessary for the early stages of colonisation allowing replication following
      cell entry. Attenuation of the Deltaeco mutant strain in the murine model of
      melioidosis further supported Ecotin as a virulence factor of B. pseudomallei. 

PMID- 24462576
TI  - MicroRNA-dependent targeting of the extracellular matrix as a mechanism of
      regulating cell behavior.
AB  - BACKGROUND: MicroRNAs are small noncoding RNAs which regulate gene expression at
      the posttranscriptional level by inducing mRNA degradation or translational
      repression. MicroRNA-dependent modulation of the extracellular matrix and its
      cellular receptors has emerged as a novel mechanism of regulating numerous matrix
      dependent processes, including cell proliferation and apoptosis, cell adhesion
      and migration, cell differentiation and stem cell properties. SCOPE OF REVIEW: In
      this review, we will present different mechanisms by which microRNAs and
      extracellular matrix constituents mutually regulate their expression, and we will
      demonstrate how these expression changes affect cell behavior. We will also
      highlight the importance of dysregulated matrix-related microRNA expression for
      the pathogenesis of inflammatory and malignant disease, and discuss the potential
      for diagnostic and therapeutic applications. MAJOR CONCLUSIONS: MicroRNAs and
      matrix-dependent signal transduction processes form novel regulatory circuits,
      which profoundly affect cell behavior. As misexpression of microRNAs targeting
      extracellular matrix constituents is observed in a variety of diseases, a
      pharmacological intervention with these processes has therapeutic potential, as
      successfully demonstrated in vitro and in advanced animal models. However, a
      deeper mechanistic understanding is required to address potential side effects
      prior to clinical applications in humans. GENERAL SIGNIFICANCE: A full
      understanding of the role and function of microRNA-dependent regulation of the
      extracellular matrix may lead to new targeted therapies and new diagnostics for
      malignant and inflammatory diseases in humans. This article is part of a Special
      Issue entitled Matrix-mediated cell behaviour and properties.

PMID- 24462577
TI  - Systemic lupus erythematosus: molecular cloning of fourteen recombinant DNase
      monoclonal kappa light chains with different catalytic properties.
AB  - BACKGROUND: DNase antibodies can play an important role in the pathogenesis of
      different autoimmune pathologies. METHODS: An immunoglobulin light chain phagemid
      library derived from peripheral blood lymphocytes of patients with systemic lupus
      erythematosus (SLE) was used. The small pools of phage particles displaying DNA
      binding light chains with different for DNA were isolated by affinity
      chromatography on DNA-cellulose and the fraction eluted with 0.5M NaCl was used
      for preparation of individual monoclonal light chains (MLChs, 28kDa). Forty-five
      of 451 individual colonies were randomly chosen for a study of MLChs with DNase
      activity. The clones were expressed in Escherichia coli in a soluble form, and
      MLChs were purified by metal chelating chromatography followed by gel filtration,
      and studied in detail. RESULTS: Fifteen of 45 MLChs efficiently hydrolyzed DNA,
      and fourteen of them demonstrated various optimal concentrations of KCl or NaCl
      in a 1-100mM range and showed one or two pH optima in a 4.8-9.1 range. All MLChs
      were dependent on divalent metal cations: the ratio of relative DNase activity in
      the presence of Mn(2+), Ca(2+), Mg(2+), Ni(2+), Zn(2+), Cu(2+), and Co(2+) was
      individual for each MLCh preparation. Fourteen MLChs demonstrated a comparable
      affinity for DNA (260-320nM), but different kcat values (0.02-0.7min(-1)).
      CONCLUSIONS: These observations suggest an extreme diversity of DNase abzymes
      from SLE patients. GENERAL SIGNIFICANCE: SLE light chain repertoire can serve as
      a source of new types of DNases.

PMID- 24462578
TI  - Diagnosis and molecular basis of mitochondrial respiratory chain disorders: exome
      sequencing for disease gene identification.
AB  - Mitochondrial disorders have the highest incidence among congenital metabolic
      diseases, and are thought to occur at a rate of 1 in 5000 births. About 25% of
      the diseases diagnosed as mitochondrial disorders in the field of pediatrics have
      mitochondrial DNA abnormalities, while the rest occur due to defects in genes
      encoded in the nucleus. The most important function of the mitochondria is
      biosynthesis of ATP. Mitochondrial disorders are nearly synonymous with
      mitochondrial respiratory chain disorder, as respiratory chain complexes serve a
      central role in ATP biosynthesis. By next-generation sequencing of the exome, we
      analyzed 104 patients with mitochondrial respiratory chain disorders. The results
      of analysis to date were 18 patients with novel variants in genes previously
      reported to be disease-causing, and 27 patients with mutations in genes suggested
      to be associated in some way with mitochondria, and it is likely that they are
      new disease-causing genes in mitochondrial disorders. This article is part of a
      Special Issue entitled Frontiers of Mitochondrial Research. 

PMID- 24462579
TI  - Developmentally regulated collagen/integrin interactions confer adhesive
      properties to early postnatal neural stem cells.
AB  - BACKGROUND: It is becoming increasingly apparent that the extracellular matrix
      acts as an important regulator of the neural stem niche. Previously we found that
      neural stem and progenitor cells (NSPCs) derived from the early postnatal
      subventricular zone of mice adhere to a collagen/hyaluronan hydrogel, whereas
      NSPCs from the adult and embryonic brain do not. METHODS: To examine the specific
      adhesive properties of young stem cells in more detail, NSPCs isolated from
      embryonic, postnatal day 6 (P6), and adult mouse brains were cultured on collagen
      I. RESULTS: Early postnatal NSPCs formed paxillin-positive focal adhesions on
      collagen I, and these adhesions could be prevented by an antibody that blocked
      integrin beta1. Furthermore, we found the corresponding integrin alpha subunits
      alpha2 and alpha11 levels to be highest at the postnatal stage. Gene ontology
      analysis of differentially expressed genes showed higher expression of
      transcripts involved in vasculature development and morphogenesis in P6 stem
      cells, compared to adult. CONCLUSIONS: The ability to interact with the
      extracellular matrix differs between postnatal and adult NSPCs. GENERAL
      SIGNIFICANCE: Our observations that the specific adhesive properties of early
      postnatal NSPCs, which are lost in the adult brain, can be ascribed to the
      integrin subunits expressed by the former furthering our understanding of the
      developing neurogenic niche. This article is part of a Special Issue entitled
      Matrix-mediated cell behaviour and properties.

PMID- 24462580
TI  - WITHDRAWN: Hazard assessment of nitrosamine and nitramine by-products of amine
      based CCS: an alternative approach.
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- 24462581
TI  - Randomized clinical trial of disulfiram for cocaine dependence or abuse during
      buprenorphine treatment.
AB  - BACKGROUND: Disulfiram may be efficacious for treating cocaine dependence or
      abuse, possibly through inhibiting dopamine beta-hydroxylase (DbetaH).
      Consequently, this randomized, placebo-controlled clinical trial of disulfiram
      during buprenorphine maintenance treatment evaluated the study hypothesis that
      disulfiram is superior to placebo and explored whether disulfiram response is
      greatest for participants with a single nucleotide polymorphism coding for
      genetically low DbetaH (T-allele carriers). METHODS: We randomized 177
      buprenorphine-treated opioid dependent participants with cocaine dependence or
      abuse to 12 weeks of double-blind treatment with disulfiram 250mg daily (n=91) or
      placebo (n=86). Of 155 participants genotyped, 84 were CC-homozygous, and 71 CT
      or TT genotypes. Primary outcomes included days per week cocaine use, number of
      cocaine-negative urine tests, and maximum consecutive weeks of cocaine
      abstinence. We analyzed an intention-to-treat comparison between disulfiram and
      placebo. We also explored potential pharmacogenetic interactions and examined
      treatment responses of four participant groups based on medication (disulfiram or
      placebo) by genotype (CC-homozygous or T-allele carrier) classification. RESULTS:
      Disulfiram participants reported significantly less frequent cocaine use; the
      differences in cocaine-negative urine tests or consecutive weeks abstinence were
      not significant. Frequency of cocaine use was lowest in disulfiram-treated T
      allele carriers; differences in cocaine-negative urine tests or consecutive weeks
      abstinence were not significant among the four medication-genotype groups.
      CONCLUSIONS: The findings provide limited support for the efficacy of disulfiram
      for reducing cocaine use and suggest that its mechanism of action may involve
      inhibition of DbetaH. Further studies of its efficacy, mechanism of action, and
      pharmacogenetics of response are warranted.

PMID- 24462582
TI  - The expression of neurotrophins is differentially regulated by omega-3
      polyunsaturated fatty acids at weaning and postweaning in C57BL/6 mice cerebral
      cortex.
AB  - Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and neurotrophins are pivotal to
      the proper functioning of the central nervous system. We investigated the effects
      of perinatal and postweaning n-3 PUFA diets on cerebral cortical phospholipid
      fatty acid composition, and the expression of neurotrophins at weaning and 16
      weeks postweaning of the male offspring of C57BL/6 mice. Female C57BL/6 mice were
      fed semi-purified diets (20%w/w fat) containing 10% (high) and 2% (low) n-3 PUFA
      before mating, during pregnancy, and until weaning. Offspring were studied at
      weaning and 16 weeks postweaning on their mother's designated diet. Cerebral
      cortical phospholipid fatty acids and mRNA expressions of brain-derived
      neurotrophic factor (BDNF), nerve growth factor (NGF), cAMP response element
      binding protein (CREB), and TrkB were measured. The protein concentration of
      phosphorylated CREB (pCREB) was determined by ELISA. DHA and total n-3 PUFA were
      significantly higher in cortical phospholipids of the high n-3 PUFA group
      compared to the low n-3 PUFA group (P<0.0001), and increased significantly from
      weaning to 16 weeks (P<0.0001). There was a significant effect of diet (P<0.05)
      and age (P<0.05) on the mRNA expression of NGF. The mRNA expression of BDNF
      increased significantly (P<0.01) in the high n-3 PUFA group compared to the low n
      3 PUFA group. The mRNA expression of TrKB was significantly higher (P<0.0001) at
      16 weeks in the high n-3 PUFA group compared to the low n-3 PUFA group; however,
      no difference was observed at weaning. pCREB/Total CREB was higher in the high n
      3 PUFA group compared to the low n-3 PUFA group (P<0.05). Our findings
      demonstrate that perinatal and postweaning diets high in n-3 PUFA lead to
      accretion of n-3 PUFA in brain cortex. We further found that n-3 PUFA upregulates
      the expression of neurotrophins and their target receptors in an age dependent
      fashion.

PMID- 24462583
TI  - Serotonin-induced down-regulation of cell surface serotonin transporter.
AB  - The serotonin transporter (SERT) terminates serotonergic signaling and enables
      refilling of synaptic vesicles by mediating reuptake of serotonin (5-HT) released
      into the synaptic cleft. The molecular and cellular mechanisms controlling SERT
      activity and surface expression are not fully understood. Here we demonstrate
      that the substrate 5-HT itself causes acute down-regulation of SERT cell surface
      expression. To assess surface SERT expression by ELISA, we used a SERT variant
      (TacSERT) where the N-terminus of SERT was fused to the intracellular tail of the
      extracellularly FLAG-tagged single-membrane spanning protein Tac. In stably
      transfected HEK293 cells, 5-HT caused a dose-dependent reduction in TacSERT
      surface signal with an EC50 value equivalent to the Km value observed for 5-HT
      uptake. The 5-HT-induced reduction in surface signal reached maximum within 40
      60min and was blocked by the selective SERT inhibitor S-citalopram. 5-HT-induced
      reduction in SERT expression was further supported by surface biotinylation
      experiments showing 5-HT-induced reduction in wild type SERT plasma membrane
      levels. Moreover, preincubation with 5-HT lowered the Vmax for 5-HT uptake in
      cultured raphe serotonergic neurons, indicting that endogenous cell-surface
      resident SERT likewise is down-regulated in the presence of substrate. 

PMID- 24462584
TI  - Tetramethylpyrazine analogue CXC195 protects against cerebral
      ischemia/reperfusion-induced apoptosis through PI3K/Akt/GSK3beta pathway in rats.
AB  - CXC195 showed strongest protective effects among the ligustrazine derivatives in
      cells and prevented apoptosis induced by H2O2 injury. We recently demonstrated
      that CXC195 protected against cerebral ischemia/reperfusion (I/R) injury by its
      antioxidant activity. However, whether the anti-apoptotic action of CXC195 is
      involved in cerebral I/R injury is unknown. Here, we investigated the role of
      CXC195 in apoptotic processes induced by cerebral I/R and the possible signaling
      pathways. Male Wistar rats were submitted to transient middle cerebral artery
      occlusion for 2h, followed by 24h reperfusion. CXC195 was injected
      intraperitoneally at 2h and 12h after the onset of ischemia. The number of
      apoptotic cells was measured by TUNEL assay, apoptosis-related protein cleaved
      caspase-3, Bcl-2, Bax and the phosphorylation levels of Akt and GSK3beta in
      ischemic penumbra were assayed by western blot. The results showed that
      administration of CXC195 at the doses of 3mg/kg and 10mg/kg significantly
      inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing
      the level of cleaved caspase-3 and Bax, and increasing the level of Bcl-2 in rats
      subjected to I/R injury. Simultaneously, CXC195 treatment markedly increased the
      phosphorylation of Akt and GSK3beta. Blockade of PI3K activity by wortmannin,
      dramatically abolished its anti-apoptotic effect and lowered both Akt and
      GSK3beta phosphorylation levels. Our study firstly demonstrated that CXC195
      protected against cerebral I/R injury by reducing apoptosis in vivo and
      PI3K/Akt/GSK3beta pathway involved in the anti-apoptotic effect. 

PMID- 24462585
TI  - Establishment of heart teams in Portugal.
AB  - Whenever several therapeutic options exist, multidisciplinary decision-making is
      beneficial for the patient and for society at large. The main obstacles to the
      establishment of heart teams in Portugal are organizational and logistical.
      Implementing a heart team approach entails definition of the situations requiring
      multidisciplinary discussion, creation of clear lines of communication, written
      protocols and obtaining patient informed consent. The European Society of
      Cardiology guidelines define the clinical scenarios where intervention of the
      heart team is recommended. 

PMID- 24462586
TI  - Application of stable isotopes to investigate the metabolism of fatty acids,
      glycerophospholipid and sphingolipid species.
AB  - Nature provides an enormous diversity of lipid molecules that originate from
      various pathways. To gain insight into the metabolism and dynamics of lipid
      species, the application of stable isotope-labeled tracers combined with mass
      spectrometric analysis represents a perfect tool. This review provides an
      overview of strategies to track fatty acid, glycerophospholipid, and sphingolipid
      metabolism. In particular, the selection of stable isotope-labeled precursors and
      their mass spectrometric analysis is discussed. Furthermore, examples of
      metabolic studies that were performed in cell culture, animal and clinical
      experiments are presented. 

PMID- 24462587
TI  - Lipid requirements for entry of protein toxins into cells.
AB  - The plant toxin ricin and the bacterial toxin Shiga toxin both belong to a group
      of protein toxins having one moiety that binds to the cell surface, and another,
      enzymatically active moiety, that enters the cytosol and inhibits protein
      synthesis by inactivating ribosomes. Both toxins travel all the way from the cell
      surface to endosomes, the Golgi apparatus and the ER before the ribosome
      inactivating moiety enters the cytosol. Shiga toxin binds to the neutral
      glycosphingolipid Gb3 at the cell surface and is therefore dependent on this
      lipid for transport into the cells, whereas ricin binds both glycoproteins and
      glycolipids with terminal galactose. The different steps of transport used by
      these toxins have specific requirements for lipid species, and with the recent
      developments in mass spectrometry analysis of lipids and microscopical and
      biochemical dissection of transport in cells, we are starting to see the
      complexity of endocytosis and intracellular transport. In this article we
      describe lipid requirements and the consequences of lipid changes for the entry
      and intoxication with ricin and Shiga toxin. These toxins can be a threat to
      human health, but can also be exploited for diagnosis and therapy, and have
      proven valuable as tools to study intracellular transport. 

PMID- 24462588
TI  - Perforated intraperitoneal intrauterine contraceptive devices: diagnosis,
      management, and clinical outcomes.
AB  - STUDY OBJECTIVE: To describe a series of intraperitoneal perforated intrauterine
      contraception devices (IUDs) and to discuss associated findings, methods for
      diagnosis, and management of this complication. DESIGN: Retrospective review of
      surgical database between 1998 and 2012 (Canadian Task Force classification II
      2). SETTING: University medical center. PATIENTS: Thirty-seven women with a
      perforated IUD in the intraperitoneal cavity. MEASUREMENTS AND MAIN RESULTS:
      Nineteen copper IUDs (51%), 17 levonorgestrel-releasing IUDs (LNG-IUDs) (46%),
      and 1 Lippes loop (3%) were identified. Twenty women (54%) had abdominal pain, 16
      (43%) had no symptoms, and 1 (3%) was found to have strings protruding from her
      anus. Twenty-six women (70%) underwent laparoscopy to remove the IUD, and 6 (16%)
      underwent hysteroscopy along with laparoscopy. Conversion to laparotomy was
      required in 4 patients (11%). Two IUDs (5%) caused full-thickness rectouterine
      fistulas that required laparotomy for repair. Dense adhesions were found in 21
      women (57%); and of those, 15 (71%) were associated with a copper IUD. Copper
      IUDs were significantly more likely than LNG-IUDs to be associated with dense
      adhesions (p = .02). CONCLUSIONS: Perforated IUDs can be asymptomatic or cause
      short-term and long-term symptoms. Long-term complications include abscess and
      fistula formation. Copper IUDs cause a greater inflammatory process than do LNG
      IUDs. Even if asymptomatic, we advocate prompt removal of all IUDs that perforate
      into the peritoneal cavity once they are identified. Laparoscopic surgical
      removal of an intraperitoneal IUD is a safe and preferred method.

PMID- 24462589
TI  - Gynecologic surgery in the obese patient.

PMID- 24462590
TI  - Electromechanical morcellators in minimally invasive gynecologic surgery: an
      update.
AB  - STUDY OBJECTIVE: To assess all electromechanical morcellators used in gynecology
      to achieve an objective comparison between them and to make suggestions for
      improvements in future developments. DESIGN: Literature review. INTERVENTION: The
      PubMed, Web of Science, EMBASE, and MAUDE databases were systematically searched
      for all available literature using the terms "morcellator," "morcellators,"
      "morcellate," "morcellation," and "morcellated." All articles with information on
      morcellation time and morcellated tissue mass or the calculated morcellation rate
      of electromechanical morcellators used for gynecologic laparoscopic surgery were
      included. For general data of an existing morcellator, the manufacturer was
      contacted and Google was searched. Data for morcellation rate, type of procedure,
      and general characteristics were compared. MEASUREMENTS AND MAIN RESULTS: Seven
      articles were suitable for analysis, and 11 different morcellators were found. In
      the past decades the morcellation rate has increased. The described morcellation
      rate ranged from 6.2 to 40.4 g/min. Motor peeling is currently the fastest
      working principle. Comparing hysterectomy and myomectomy per device, the
      Morcellex and Rotocut morcellators demonstrated a higher morcellation rate for
      myomectomy, 25.9 vs 30 g/min and 28.4 vs 33.1 g/min, respectively, although the X
      Tract morcellator showed a higher rate for hysterectomy, 14.2 vs 11.7 g/min.
      CONCLUSION: Over the years, the morcellator has improved with respect to the
      morcellation rate. However, the morcellation process still has limitations,
      including tissue scattering, morcellator-related injuries, and the inevitable
      small blade diameter, which all come at the expense of the morcellation rate and
      time. Therefore, development of improved morcellators is required, with
      consideration of the observed limitations.

PMID- 24462591
TI  - Development and validation of a laparoscopic sacrocolpopexy simulation model for
      surgical training.
AB  - STUDY OBJECTIVE: To develop a valid laparoscopic sacrocolpopexy simulation model
      for use as an assessment and learning tool for performing this procedure. DESIGN:
      Simulation study (Canadian Task Force classification II-2). SETTING: Two tertiary
      academic centers. INTERVENTION: A training model was developed to simulate
      performance of a laparoscopic sacrocolpopexy. Construct validity was measured by
      comparing observed masked performances on the model between experienced Female
      Pelvic Medicine and Reconstructive Surgeons (experts) and upper level trainees.
      All videotaped performances were scored by 2 surgeons who were masked to subject
      identity and using the valid and reliable Global Operative Assessment of
      Laparoscopic Skills scale. MEASUREMENTS AND MAIN RESULTS: The expert group
      included Female Pelvic Medicine and Reconstructive Surgeons (n = 5) experienced
      in laparoscopic sacrocolpopexy, and the trainee group (n = 15) included fourth
      year gynecology residents (n = 5) and fellows in Female Pelvic Medicine and
      Reconstructive Surgery and in Minimally Invasive Gynecologic Surgery (n = 10).
      The experts performed significantly better than the trainees in total score and
      in every domain of the Global Operative Assessment of Laparoscopic Skills scale
      (median [range] score: expert group, 33 [30.5-39] vs. trainee group, 20.5 [13.5
      30.5]; p = .002). Previous surgical experience had a strong association with
      performance on the model (rho > 0.75). Most subjects "agreed" or "strongly
      agreed" that the model was authentic to the live procedure and a useful training
      tool. There was strong agreement between masked raters (interclass correlation
      coefficient 0.84). CONCLUSION: This simulation model is valid and reliable for
      assessing performance of laparoscopic sacrocolpopexy and may be used for
      practicing key steps of the procedure.

PMID- 24462592
TI  - The impact of adnexal torsion on antral follicle count when compared with
      contralateral ovary.
AB  - STUDY OBJECTIVE: In women with adnexal torsion, there is an absence of data
      whether ovarian reserve is affected when treated by detorsion and conservative
      surgery. We aimed to evaluate ovarian reserve by counting the antral follicles
      and estimating the ovarian volume in the operated side compared with the
      contralateral ovary. DESIGN: A case-control study (Canadian Task Force
      classification II-2). SETTING: In vitro fertilization center, Hacettepe
      University Faculty of Medicine and Etlik Zubeyde Hanim Women's Health and
      Research Hospital, Ankara, Turkey. PATIENTS: Patients who underwent conservative
      surgery because of adnexal torsion between January 2008 and August 2012 were
      retrospectively investigated from patient files and computer-based data. Eighteen
      patients were eligible for the study protocol and further evaluated for their
      ovarian reserve with ultrasonography. INTERVENTIONS: Comparing ovarian reserve in
      the torsioned and contralateral sides with ultrasonography by physicians who were
      blind to the previously operated side. MEASUREMENT AND MAIN RESULTS: The mean age
      was 28.3 +/- 5.8 years. The mean antral follicle count on the operated and
      contralateral ovaries were 12.3 +/- 8.4 and 11.3 +/- 7.4, respectively (p = .23).
      The respective figure for ovarian volume was 7.6 +/- 4.2 and 9.1 +/- 5.3 mL (p =
      .063). Among 3 patients seeking to become pregnant, 1 of them conceived
      spontaneously and one achieved pregnancy with clomiphene citrate use. CONCLUSION:
      The finding of the current study suggests that ovarian reserve reflected by the
      antral follicle count is not compromised in patients treated with detorsion of
      the twisted adnexa.

PMID- 24462593
TI  - Sacrocolpopexy for treatment of vaginal apical prolapse: evidence-based surgery.
AB  - Pelvic organ prolapse is a common condition that negatively affects womens'
      quality of life. Sacrocolpopexy is an abdominal procedure designed to treat
      apical compartment prolapse including uterine or vaginal vault prolapse and
      multiple-compartment prolapse. Although traditionally performed as an open
      abdominal procedure, minimally invasive sacrocolpopexy, whether laparoscopic or
      robotic, has been successfully adopted in the practice of many pelvic
      reconstructive surgeons. There are many variations to this procedure, with
      different levels of evidence to support each of them. Herein we review the
      current literature on sacrocolpopexy, with emphasis on the minimally invasive
      approach. Procedural steps and controversies are examined in light of the
      existing literature, and recommendations are made on the basis of the level of
      existing evidence. 

PMID- 24462594
TI  - Natural orifice transluminal endoscopic surgery-assisted versus single-port
      laparoscopic-assisted vaginal hysterectomy: a case-matched study.
AB  - OBJECTIVE: Natural orifice transluminal endoscopic surgery (NOTES) is currently a
      very important procedure for surgeons. This study aimed to describe the initial
      clinical experience of NOTES-assisted vaginal hysterectomy (NAVH) and to
      investigate its feasibility and surgical outcomes compared with single-port
      laparoscopic-assisted vaginal hysterectomy (SP-LAVH). DESIGN: Retrospective chart
      analysis (Canadian Task Force classification II-1). SETTING: One university
      affiliated hospital. PATIENTS: Women undergoing NAVH or SP-LAVH for benign
      uterine diseases. INTERVENTION: NAVH using a novel homemade NOTES system
      comprised a glove-wound retractor NOTES port or SP-LAVH using conventional
      laparoscopic instruments and an umbilical glove port. MEASUREMENTS AND MAIN
      RESULTS: Since July 2012, 16 patients with benign uterine disease have undergone
      NAVH. Another 32 paired, SP-LAVH patients from the registered database were used
      to compare these 2 modalities of laparoscopic-assisted techniques for vaginal
      hysterectomy. All NAVHs were completed successfully without the need of an
      additional port or conversion to the standard laparoscopic approach.
      Intraoperative and postoperative surgical outcomes were assessed in both groups
      of patients. There was also no significant difference between both groups in
      perioperative outcomes such as estimated blood loss, decrease in hemoglobin on
      postoperative day 1, amount of analgesic drugs used, postoperative visual analog
      scale pain score, and febrile complications, except for operative time and length
      of postoperative hospital stay. The mean operative time was 70.6 +/- 12.8 minutes
      for NAVH and 93.2 +/- 21.4 minutes for SP-LAVH (p < .001). The median
      postoperative hospital stay was 3.5 days (range, 3-5) for NAVH and 4 days (range,
      3-6) for SP-LAVH (p < .001). CONCLUSION: The findings show that NAVH is a
      feasible and safe surgical technique and has a short operative time and
      postoperative hospital stay compared with SP-LAVH. This new technique at least
      offers similar surgical outcomes and superior cosmesis in our opinion compared
      with SP-LAVH. However, prospective studies are needed to determine its full
      clinical application.

PMID- 24462595
TI  - Urinary tract injuries in laparoscopic hysterectomy: a systematic review.
AB  - The aim of this review was to estimate the incidence of urinary tract injuries
      associated with laparoscopic hysterectomy and describe the long-term sequelae of
      these injuries and the impact of early recognition. Studies were identified by
      searching the PubMed database, spanning the last 10 years. The key words "ureter"
      or "ureteral" or "urethra" or "urethral" or "bladder" or "urinary tract" and
      "injury" and "laparoscopy" or "robotic" and "gynecology" were used. Additionally,
      a separate search was done for "routine cystoscopy" and "gynecology." The
      inclusion criteria were published articles of original research referring to
      urologic injuries occurring during either laparoscopic or robotic surgery for
      gynecologic indications. Only English language articles from the past 10 years
      were included. Studies with less than 100 patients and no injuries reported were
      excluded. No robotic series met these criteria. A primary search of the database
      yielded 104 articles, and secondary cross-reference yielded 6 articles. After
      reviewing the abstracts, 40 articles met inclusion criteria and were reviewed in
      their entirety. Of those 40 articles, 3 were excluded because of an inability to
      extract urinary tract injuries from total injuries. Statistical analysis was
      performed using a generalized linear mixed effects model. The overall urinary
      tract injury rate for laparoscopic hysterectomy was 0.73%. The bladder injury
      rate ranged from 0.05% to 0.66% across procedure types, and the ureteral injury
      rate ranged from 0.02% to 0.4% across procedure type. In contrast to earlier
      publications, which cited unacceptably high urinary tract injury rates,
      laparoscopic hysterectomy appears to be safe regarding the bladder and ureter. 

PMID- 24462596
TI  - Safety of perioperative aspirin therapy in minimally invasive endometrial cancer
      staging.
AB  - STUDY OBJECTIVE: To investigate if low-dose aspirin influences the risk of
      bleeding and hemorrhagic complications during minimally invasive surgical staging
      for endometrial cancer. DESIGN: Retrospective study (Canadian Task Force
      classification II-2.) SETTING: University teaching hospital. PATIENTS: Three
      hundred seventeen endometrial cancer patients undergoing laparoscopic staging.
      INTERVENTIONS: Laparoscopic surgical staging included total laparoscopic
      hysterectomy plus bilateral salpingo-oophorectomy +/- retroperitoneal staging.
      MEASUREMENT AND MAIN RESULTS: Forty-three (14%) low-dose aspirin users were
      compared with 274 (86%) nonaspirin users. Aspirin-treated patients were older
      than patients in the control group (71 [range, 50-85] vs. 64 [range, 27-92] years
      old, p < .001). No between-group differences in intraoperative bleeding (p =
      .32), hemoglobin drop (p = .91), transfusions (p = .09), and hemorrhagic
      complications rate (p = .58) were recorded. Aspirin users had a lower
      lymphadenectomy rate in comparison with patients in the control group (p = .001).
      However, according to a subanalysis of patients undergoing retroperitoneal
      staging (20 aspirin users vs. 200 patients in the control group), no differences
      in bleeding (p = .53), hemorrhagic complications (p = 1.0), or transfusion rate
      (p = .25) were observed. CONCLUSION: Low-dose aspirin does not influence the risk
      of bleeding and hemorrhagic complications in endometrial cancer patients
      undergoing minimally invasive staging. Hence, the choice to continue or cease the
      use of low-dose aspirin should be guided only by perioperative cardiovascular
      risk stratification.

PMID- 24462597
TI  - Peritoneal nodules after laparoscopic surgery with uterine morcellation: review
      of a rare complication.
AB  - The risk of occult malignancy being present at the time of uterine morcellation
      has been estimated to be about 1%. Dissemination of both benign and malignant
      disease may occur after morcellation, leading to a variety of peritoneal nodules.
      These lesions are reviewed. 

PMID- 24462598
TI  - The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription.
AB  - Recent evidences indicated Nrf2 is more potent than Nrf1 in the activation of
      antioxidant genes. However, the roles of Nrf proteins in the regulation of copper
      responsive transcription have not been well addressed. We took the toxicogenomic
      approach and the present network and Gene Ontology analyses results showed that
      Nrf1 and Nrf2 are distinctively involved in copper-responsive transcriptional
      regulation in HepG2 transcriptome. Cells deficient in either Nrf1 or Nrf2 were
      more susceptible to copper exposure than wild type cells. Nrf1 and Nrf2 null
      cells were transfected with the luciferase reporters containing either ARE(s) or
      a combination of ARE(s) and MREs, and then treated with copper. In Nrf2-null
      (Nrf2(-/-)) cells, copper did not activate transcription of reporter genes,
      whereas Nrf1 deficiency did not affect copper-inducible activation. Ectopic
      expression of Nrf2 restored copper-inducible transcription in Nrf2(-/-) cells.
      However, the changes in the intrinsic mRNA levels of MT-1 in Nrf null cells
      following copper treatment showed that Nrf1 and Nrf2 equally contributed to MT-1
      activation after 4h, while Nrf1involved more than Nrf2 following 24h exposure.
      These results suggest that while Nrf2 is crucial for MRE/ARE-mediated
      transcription in response to copper, Nrf1 may activate MT-1 expression by a
      mechanism different from that Nrf2 employs. 

PMID- 24462599
TI  - AlphaII-spectrin participates in the surface expression of cell adhesion molecule
      L1 and neurite outgrowth.
AB  - AlphaII-spectrin, a basic component of the spectrin-based scaffold which
      organizes and stabilizes membrane microdomains in most animal cells, has been
      recently implicated in cell adherence and actin dynamics. Here we investigated
      the contribution of alphaIotaIota-spectrin to neuritogenesis, a highly complex
      cellular process which requires continuous actin cytoskeleton remodeling and
      cross-talk between extracellular cues and their cell surface receptors, including
      cell adhesion molecules. Using RNA interference-mediated gene silencing to down
      regulate alphaIotaIota-spectrin expression in human neuroblastoma SH-SY5Y cells,
      we observed major changes in neurite morphology and cell shape: (1) reduced mean
      length and a higher number of neurites per cell; occasional long neurites were
      thinner and displayed abnormal adhesiveness during cell migration resulting in
      frequent breaks; similar persisting adhesiveness and breaks were also observed in
      trailing edges of cell bodies; (2) irregular polygonal cell shape in parallel
      with loss of cortical F-actin from neuronal cell bodies; (3) reduction in protein
      levels of alphaIota- and betaIota-spectrins, but not betaIotaIota-spectrin (4)
      decreased global expression of adhesion molecule L1 and spectrin-binding adapter
      ankyrin-B, which links L1 to the plasma membrane. Remarkably, alphaIotaIota
      spectrin depletion affected L1 - but not NCAM - cell surface expression, and L1
      clustering at growth cones. This study demonstrates that alphaIotaIota-spectrin
      is implicated in normal morphology and adhesive properties of neuron cell bodies
      and neurites, and in cell surface expression and organization of adhesion
      molecule L1. 

PMID- 24462601
TI  - The relative role of diet and physical activity in obesity.

PMID- 24462600
TI  - Cloud-based bioinformatics workflow platform for large-scale next-generation
      sequencing analyses.
AB  - Due to the upcoming data deluge of genome data, the need for storing and
      processing large-scale genome data, easy access to biomedical analyses tools,
      efficient data sharing and retrieval has presented significant challenges. The
      variability in data volume results in variable computing and storage
      requirements, therefore biomedical researchers are pursuing more reliable,
      dynamic and convenient methods for conducting sequencing analyses. This paper
      proposes a Cloud-based bioinformatics workflow platform for large-scale next
      generation sequencing analyses, which enables reliable and highly scalable
      execution of sequencing analyses workflows in a fully automated manner. Our
      platform extends the existing Galaxy workflow system by adding data management
      capabilities for transferring large quantities of data efficiently and reliably
      (via Globus Transfer), domain-specific analyses tools preconfigured for immediate
      use by researchers (via user-specific tools integration), automatic deployment on
      Cloud for on-demand resource allocation and pay-as-you-go pricing (via Globus
      Provision), a Cloud provisioning tool for auto-scaling (via HTCondor scheduler),
      and the support for validating the correctness of workflows (via semantic
      verification tools). Two bioinformatics workflow use cases as well as performance
      evaluation are presented to validate the feasibility of the proposed approach. 

PMID- 24462602
TI  - Can we do better?

PMID- 24462603
TI  - 3D discrete angiogenesis dynamic model and stochastic simulation for the
      assessment of blood perfusion coefficient and impact on heat transfer between
      nanoparticles and malignant tumors.
AB  - Early detection of malignant tumors plays a crucial role in the survivability
      chances of the patient. Therefore, new and innovative tumor detection methods are
      constantly searched for. Tumor-specific magnetic-core nano-particles can be used
      with an alternating magnetic field to detect and treat tumors by hyperthermia.
      For the analysis of the method effectiveness, the bio-heat transfer between the
      nanoparticles and the tissue must be carefully studied. Heat diffusion in
      biological tissue is usually analyzed using the Pennes Bio-Heat Equation, where
      blood perfusion plays an important role. Malignant tumors are known to initiate
      an angiogenesis process, where endothelial cell migration from neighboring
      vasculature eventually leads to the formation of a thick blood capillary network
      around them. This process allows the tumor to receive its extensive nutrition
      demands and evolve into a more progressive and potentially fatal tumor. In order
      to assess the effect of angiogenesis on the bio-heat transfer problem, we have
      developed a discrete stochastic 3D model & simulation of tumor-induced
      angiogenesis. The model elaborates other angiogenesis models by providing high
      resolution 3D stochastic simulation, capturing of fine angiogenesis morphological
      features, effects of dynamic sprout thickness functions, and stochastic parent
      vessel generator. We show that the angiogenesis realizations produced are well
      suited for numerical bio-heat transfer analysis. Statistical study on the
      angiogenesis characteristics was derived using Monte Carlo simulations. According
      to the statistical analysis, we provide analytical expression for the blood
      perfusion coefficient in the Pennes equation, as a function of several
      parameters. This updated form of the Pennes equation could be used for numerical
      and analytical analyses of the proposed detection and treatment method. 

PMID- 24462604
TI  - Mediastinal cystic haemangiomas: a two cases report and review of the literature.
AB  - According to the literature haemangiomas are rare benign vascular tumours (less
      than 0.5% of all mediastinal tumours). Preoperative diagnosis is difficult and
      manifest as a non-specific mediastinal mass on radiologic exploration. We report
      herein two cases of mediastinal haemangioma (MH), the first was a 63 year-old man
      with a MH in the posterior mediastinum, and the second was a 53 year-old man with
      a left paracardiac haemangioma. Surgical removal was successful and the follow-up
      was free four years after surgery. 

PMID- 24462605
TI  - Resveratrol increases antioxidant defenses and decreases proinflammatory
      cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar
      rats.
AB  - Astrocytes are responsible for modulating neurotransmitter systems and synaptic
      information processing, ionic homeostasis, energy metabolism, maintenance of the
      blood-brain barrier, and antioxidant and inflammatory responses. Our group
      recently published a culture model of cortical astrocytes obtained from adult
      Wistar rats. In this study, we established an in vitro model for hippocampal
      astrocyte cultures from adult (90 days old) and aged (180 days old) Wistar rats.
      Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant,
      anti-inflammatory, anti-aging and neuroprotective effects that modulate glial
      functions. Here, we evaluated the effects of resveratrol on GSH content, GS
      activity, TNF-alpha and IL-1beta levels in hippocampal astrocytes from newborn,
      adult and aged Wistar rats. We observed a decrease in antioxidant defenses and an
      increase in the inflammatory response in hippocampal astrocytes from adult and
      aged rats compared to classical astrocyte cultures from newborn rats. Resveratrol
      prevented these effects. These findings reinforce the neuroprotective effects of
      resveratrol, which are mainly associated with antioxidant and anti-inflammatory
      activities.

PMID- 24462606
TI  - Glucose hypermetabolism in the thalamus of patients with drug-induced
      blepharospasm.
AB  - We examined the difference in cerebral function alterations between drug-induced
      blepharospasm patients and essential blepharospasm (EB) patients by using
      positron emission tomography with (18)F-fluorodeoxyglucose. Cerebral glucose
      metabolism was examined in 21 patients with drug-induced blepharospasm (5 men and
      16 women; mean age, 53.1 [range, 29-78] years), 21 essential EB patients (5 men
      and 16 women; mean age, 53.0 [range, 33-72] years) and 24 healthy subjects (6 men
      and 18 women; mean age, 57.9 [range, 22-78] years) with long-term history of
      benzodiazepines use (drug healthy subjects). Drug-induced blepharospasm patients
      developed symptoms while taking benzodiazepines or thienodiazepines. Sixty-three
      normal volunteers (15 men and 48 women; mean age, 53.6 [range, 20-70] years) were
      examined as controls. Differences between the patient groups and control group
      were examined by statistical parametric mapping. Additionally, we defined regions
      of interests on both sides of the thalamus, caudate nucleus, anterior putamen,
      posterior putamen and primary somatosensory area. The differences between groups
      were tested using two-sample t-tests with Bonferroni correction for multiple
      comparisons. Cerebral glucose hypermetabolism on both side of the thalamus was
      detected in drug-induced blepharospasm, EB patients and drug healthy subjects by
      statistical parametric mapping. In the analysis of regions of interest, glucose
      metabolism in both sides of the thalamus in the drug-induced blepharospasm group
      was significantly lower than that in the EB group. Moreover, we observed glucose
      hypermetabolism in the anterior and posterior putamen bilaterally in EB group but
      not in drug-induced blepharospasm group and drug healthy subjects. Long-term
      regimens of benzodiazepines or thienodiazepines may cause down-regulation of
      benzodiazepine receptors in the brain. We suggest that the functional brain
      alteration in drug-induced blepharospasm patients is similar to that in EB
      patients, and that alteration of the GABAergic system might be related to the
      pathology of both blepharospasm types. 

PMID- 24462607
TI  - Sensory regulation of dopaminergic cell activity: Phenomenology, circuitry and
      function.
AB  - Dopaminergic neurons in a range of species are responsive to sensory stimuli. In
      the anesthetized preparation, responses to non-noxious and noxious sensory
      stimuli are usually tonic in nature, although long-duration changes in activity
      have been reported in the awake preparation as well. However, in the awake
      preparation, short-latency, phasic changes in activity are most common. These
      phasic responses can occur to unconditioned aversive and non-aversive stimuli, as
      well as to the stimuli which predict them. In both the anesthetized and awake
      preparations, not all dopaminergic neurons are responsive to sensory stimuli,
      however responsive neurons tend to respond to more than a single stimulus
      modality. Evidence suggests that short-latency sensory information is provided to
      dopaminergic neurons by relatively primitive subcortical structures - including
      the midbrain superior colliculus for vision and the mesopontine parabrachial
      nucleus for pain and possibly gustation. Although short-latency visual
      information is provided to dopaminergic neurons by the relatively primitive
      colliculus, dopaminergic neurons can discriminate between complex visual stimuli,
      an apparent paradox which can be resolved by the recently discovered route of
      information flow through to dopaminergic neurons from the cerebral cortex, via a
      relay in the colliculus. Given that projections from the cortex to the colliculus
      are extensive, such a relay potentially allows the activity of dopaminergic
      neurons to report the results of complex stimulus processing from widespread
      areas of the cortex. Furthermore, dopaminergic neurons could acquire their
      ability to reflect stimulus value by virtue of reward-related modification of
      sensory processing in the cortex. At the forebrain level, sensory-related changes
      in the tonic activity of dopaminergic neurons may regulate the impact of the
      cortex on forebrain structures such as the nucleus accumbens. In contrast, the
      short latency of the phasic responses to sensory stimuli in dopaminergic neurons,
      coupled with the activation of these neurons by non-rewarding stimuli, suggests
      that phasic responses of dopaminergic neurons may provide a signal to the
      forebrain which indicates that a salient event has occurred (and possibly an
      estimate of how salient that event is). A stimulus-related salience signal could
      be used by downstream systems to reinforce behavioral choices. 

PMID- 24462608
TI  - Dissociation of doublecortin expression and neurogenesis in unipolar brush cells
      in the vestibulocerebellum and dorsal cochlear nucleus of the adult rat.
AB  - We have previously shown expression of the protein doublecortin (DCX) in unipolar
      brush cells (UBCs) in the dorsal cochlear nucleus and vestibulocerebellum of the
      adult rat. We also saw DCX-immunoreactive elements with the appearance of
      neuroblasts around the fourth ventricle. Expression of DCX is seen in newborn and
      migrating neurons and hence considered a correlate of neurogenesis. There were
      two interpretations of the expression of DCX in UBCs. One possibility is that
      there might be adult neurogenesis of this cell population. Adult neurogenesis is
      now well-established, but only for the dentate gyrus of the hippocampus and the
      subventricular zone. The other possibility is that there is prolonged expression
      of DCX in adult UBCs that may signal a unique role in plasticity of these
      neurons. We tested the neurogenesis hypothesis by systemic injections of
      bromodeoxyuridine (BrdU), a thymidine analog, followed by immunohistochemistry to
      examine the numbers and locations of dividing cells. We used several different
      injection paradigms, varying the dose of BrdU, the number of injections and the
      survival time to assess the possibility of neuronal birth and migration. We saw
      BrdU-labeled cells in the cerebellum and brainstem; cell division in these
      regions was confirmed by immunohistochemistry for the protein Ki67. However,
      neither the numbers nor the distribution of labeled nuclei support the idea of
      adult neurogenesis and migration of UBCs. The function of DCX expression in UBC's
      in the adult remains to be understood. 

PMID- 24462610
TI  - Role of lateral and feedback connections in primary visual cortex in the
      processing of spatiotemporal regularity - a TMS study.
AB  - Our human visual system exploits spatiotemporal regularity to interpret incoming
      visual signals. With a dynamic stimulus sequence of four collinear bars
      (predictors) appearing consecutively toward the fovea, followed by a target bar
      with varying contrasts, we have previously found that this predictable
      spatiotemporal stimulus structure enhances target detection performance and its
      underlying neural process starts in the primary visual cortex (area V1). However,
      the relative contribution of V1 lateral and feedback connections in the
      processing of spatiotemporal regularity remains unclear. In this study we
      measured human contrast detection of a briefly presented foveal target that was
      embedded in a dynamic collinear predictor-target sequence. Transcranial magnetic
      stimulation (TMS) was used to selectively disrupt V1 horizontal and feedback
      connections in the processing of predictors. The coil was positioned over a
      cortical location corresponding to the location of the last predictor prior to
      target onset. Single-pulse TMS at an intensity of 10% below phosphene
      thresholdwas delivered at 20 or 90ms after the predictor onset. Our analysis
      revealed that the delivery of TMS at both time windows equally reduced, but did
      not abolish, the facilitation effect of the predictors on target detection.
      Furthermore, if the predictors' ordination was randomized to suppress V1 lateral
      connections, the TMS disruption was significantly more evident at 20ms than at 90
      ms time window. We suggest that both lateral and feedback connections contribute
      to the encoding of spatiotemporal regularity in V1. These findings develop
      understanding of how our visual system exploits spatiotemporal regularity to
      facilitate the efficiency of visual perception. 

PMID- 24462611
TI  - [HBeAg-positive chronic hepatitis B treatment with oral antiviral agents:
      experience and results in clinical practice].
AB  - INTRODUCTION: Due to globalization and migratory movements, HBeAg+ chronic
      hepatitis B is becoming increasingly important in Spain. OBJECTIVE: To analyze
      the epidemiological features, progression, and treatment response to oral
      antiviral agents (OA) in HBeAg+ chronic hepatitis B patients in our area.
      MATERIAL AND METHODS: We analyzed 436 patients with chronic hepatitis B infection
      followed up at the Ramon y Cajal Hospital from 1990 to June 2012. RESULTS: Sixty
      five patients (14.9%) had HBeAg+ chronic hepatitis B. Seven patients in the
      immunotolerant phase were not treated, while the remaining 58 received treatment.
      Four patients were excluded: two due to severe acute hepatitis, one due to
      hepatitis C virus coinfection and another because of a Delta virus coinfection.
      Of the remaining 54 patients, 19 received interferon with or without OA, and 35
      received only OA. Two patients treated for less than 1 month were not included in
      the analysis. The analysis was finally performed in 33 patients. The mean
      duration of treatment was 46.81 months (6-138). Lamivudine was the most
      frequently prescribed drug (39.39%) followed by tenofovir (24.24%) and entecavir
      (21.21%). The mean age was 42.08+/-14 years and 75.75% (25/33) of the patients
      were male. Nineteen of 33 patients (57.57%) achieved seroconversion to anti-HBe,
      and 27.27% (9/33) showed clearance of HBsAg. There was no evidence of HBsAg
      reversion after a mean follow-up of 35.6 months. There were 8 cases of resistance
      in 7 patients: 7 to lamivudine and 1 to adefovir. CONCLUSIONS: Approximately 15%
      of chronic hepatitis B patients in our area are HBeAg+. Treatment with OA
      achieves a high seroconversion rate (57.57%) and a considerable percentage of
      HBsAg clearance (27.27%).

PMID- 24462609
TI  - Vaginal hypersensitivity and hypothalamic-pituitary-adrenal axis dysfunction as a
      result of neonatal maternal separation in female mice.
AB  - Early life stress can permanently alter functioning of the hypothalamic-pituitary
      adrenal (HPA) axis, which regulates the stress response and influences the
      perception of pain. Chronic pelvic pain patients commonly report having
      experienced childhood neglect or abuse, which increases the likelihood of
      presenting with comorbid chronic pain and/or mood disorders. Animal models of
      neonatal stress commonly display enhanced anxiety-like behaviors, colorectal
      hypersensitivity, and disruption of proper neuro-immune interactions in
      adulthood. Here, we tested the hypothesis that early life stress impacts vaginal
      sensitivity by exposing mice to neonatal maternal separation (NMS) for 3h/day
      during the first two (NMS14) or three (NMS21) postnatal weeks. As adults, female
      mice underwent vaginal balloon distension (VBD), which was also considered an
      acute stress. Before or after VBD, mice were assessed for anxiety-like behavior,
      hindpaw sensitivity, and changes in gene and protein expression related to HPA
      axis function and regulation. NMS21 mice displayed significantly increased
      vaginal sensitivity compared to naive mice, as well as significantly reduced
      anxiety-like behavior at baseline, which was heightened following VBD. NMS21 mice
      exhibited significant thermal and mechanical hindpaw hypersensitivity at baseline
      and following VBD. NMS14 mice displayed no change in anxiety-like behavior and
      only exhibited significantly increased hindpaw mechanical and thermal sensitivity
      following VBD. Centrally, a significant decrease in negative regulation of the
      HPA axis was observed in the hypothalamus and hippocampus of NMS21 mice.
      Peripherally, NMS and VBD affected the expression of inflammatory mediators in
      the vagina and bladder. Corticotropin-releasing factor (CRF) receptor and
      transient receptor potential (TRP) channel protein expression was also
      significantly, and differentially, affected in vagina, bladder, and colon by both
      NMS and VBD. Together these data indicate that NMS affects both central and
      peripheral aspects of the HPA axis, which may drive changes in vaginal
      sensitivity and the development of comorbid chronic pain and mood disorders. 

PMID- 24462612
TI  - [Sock-line hyperpigmentation].

PMID- 24462613
TI  - An intrathecal catheter in a pregnant patient with idiopathic intracranial
      hypertension: analgesia, monitor and therapy?
AB  - Idiopathic intracranial hypertension is important for the obstetric anaesthetist
      as it is mostly seen in obese women of childbearing age. The incidence is likely
      to increase as the obesity pandemic grows. Management of labour analgesia in
      these patients can be complex and requires multidisciplinary input. We
      successfully managed labour analgesia in a parturient with idiopathic
      intracranial hypertension with an intrathecal catheter. The possibility of using
      this catheter as a cerebrospinal fluid drain and pressure monitor was considered
      and is discussed along with potential complications. 

PMID- 24462614
TI  - The severed epidural catheter.

PMID- 24462615
TI  - Combined interscalene-superficial cervical plexus blocks for surgical repair of a
      clavicular fracture in a 15-week pregnant woman.

PMID- 24462616
TI  - The incidence and management of inability to advance Arrow FlexTip Plus epidural
      catheters in obstetric patients.
AB  - BACKGROUND: Difficulty advancing epidural catheters is troublesome to obstetric
      anesthesiologists. Flexible epidural catheters have been shown to reduce
      paresthesiae and intravascular catheter placement in parturients, but the cause
      of inability to advance these catheters past the epidural needle tip remains
      undefined. Specifically, its incidence and effective management strategies have
      not been described. METHODS: All labor epidural catheters were recorded for a 22
      week period. Difficulty advancing the epidural catheter was defined as an
      inability to advance the catheter beyond the needle tip after obtaining loss of
      resistance. Anesthesiologists completed a survey when difficulty advancing a
      catheter occurred. RESULTS: A total of 2148 epidural catheter placements were
      performed. There were 97 cases of an inability to advance the epidural catheter
      (4.5%, 95% CI 3.7 to 5.5%). This occurred in 4.2% of combined spinal-epidural and
      4.6% of epidural placements (OR 0.92, 95% CI 0.53 to 1.62). On a 0 to 10scale,
      the median [IQR] provider confidence in loss of resistance was 9 [8, 10]. A total
      of 230 corrective maneuvers were performed, using nine distinct approaches. The
      incidence of accidental dural puncture was 3.1% if an inability to advance
      occurred (n=97) compared to 1.2% for other placements (n=2051, P=0.12).
      DISCUSSION: Inability to advance Arrow FlexTip Plus(r) epidural catheters was
      relatively common (4.5%) and occurred despite confidence in obtaining loss of
      resistance. Injecting saline may be corrective and appears to have little
      disadvantage. However, removing the needle and performing a new placement was the
      most successful corrective maneuver.

PMID- 24462619
TI  - Active rehabilitation in a pediatric extracorporeal membrane oxygenation patient.
AB  - Decreased intensive care unit (ICU) mortality has led to an increase in ICU
      morbidity. ICU-induced immobilization plays a major role in this morbidity.
      Recently, ICU mobility has been shown to be safe and effective in adolescent and
      adult patients. We report the successful rehabilitation of an 8-year-old boy with
      severe acute respiratory distress syndrome on extracorporeal membrane
      oxygenation. A child who is critically ill may safely perform active
      rehabilitation while on venovenous extracorporeal membrane oxygenation. The gains
      achieved through active rehabilitation and optimal nutrition can facilitate
      recovery from severe acute respiratory distress syndrome in select pediatric
      patients on extracorporeal membrane oxygenation. 

PMID- 24462618
TI  - A tract-based spatial statistics study in anorexia nervosa: abnormality in the
      fornix and the cerebellum.
AB  - There has been an increasing interest in white matter abnormalities in patients
      with anorexia nervosa (AN). However, to date, there have been only a few
      diffusion tensor imaging (DTI) studies investigating AN, and the results are
      inconsistent. In this study, we employed tract-based spatial statistics (TBSS), a
      robust technique for whole-brain analysis of DTI data, to detect white matter
      abnormalities in AN patients compared with healthy controls. Seventeen women with
      AN and 18 age matched healthy women were included. The mean body mass index of
      patients was 13.6 kg/m(2) (controls: 19.9 kg/m(2)). DTI data were acquired on a 3
      Tesla magnetic resonance imaging system. Fractional anisotropy (FA) and mean
      diffusivity (MD) maps were calculated from the DTI data of each patient, and
      voxel-wise group comparisons of FA and MD were performed using TBSS. Compared
      with the healthy comparisons, the patients showed a significantly higher MD value
      in the fornix and lower FA value in the left cerebellum. We also found
      significant positive correlations between the mean FA value of the left
      cerebellar hemisphere cluster and BMI, as well as between the mean MD value of
      the cluster in the anterior body of the fornix and the duration of illness. The
      results suggest that the white matter abnormalities in the fornix and the
      cerebellum may be related to the pathophysiology of AN.

PMID- 24462617
TI  - PCBs and ADHD in Mohawk adolescents.
AB  - The present study examines the relationship between the levels of persistent
      polychlorinated biphenyls (PCBs) in adolescents' blood serum and concurrent
      measures of their ADHD-like behavior derived from ratings provided by parents and
      teachers. Two measures with demonstrated diagnostic validity, the Conners and
      ADDES scales, are used. The study was conducted in partnership with the Mohawk
      Nation at Akwesasne where the St. Lawrence River and surrounding waterways have
      been contaminated with PCBs that have entered the food chain. This study examines
      a subset of the data derived from the Mohawk Adolescent Well-Being Study (MAWBS),
      which was designed to investigate psychosocial and health related outcomes of 271
      adolescents aged 10 years to 17 years and whose mothers were likely to have
      consumed PCB-contaminated fish and wild game before and during their pregnancy.
      No evidence of negative effects of adolescent blood PCB levels on ADHD-like
      behavior was found, and indeed occasional findings were in the unexpected
      direction. The possibility of negative confounding by SES and breastfeeding
      history was examined but dismissed.

PMID- 24462620
TI  - Long-lasting glutamatergic modulation induced by neonatal GABA enhancement in
      mice.
AB  - A subgroup of anticonvulsant and neuroleptic drugs acts through the potentiation
      of GABA pathways. The regulatory role of GABA in neuronal circuit formation is
      related to its depolarizing action that supports activity-dependent
      synaptogenesis. We hypothesized that elevated levels of GABA in the immature
      brain modify synaptogenesis in excitatory synapses and consequently affect mice
      behavior. In support of this theory, we showed previously that neonatal exposure
      to a GABA-transaminase inhibitor (Vigabatrin, GVG) modifies the expression of
      presynaptic proteins and suppresses excitatory synaptic potentials. To further
      characterize this phenomenon, we examined the effect of GVG applied during
      postnatal days 4-14, during the switch in GABA function from a depolarizing to a
      hyperpolarizing substance, on the development of excitatory synapses and mice
      sociability. Early exposure to GVG induced differential effects on synaptic
      proteins in the hippocampus and the cerebral cortex, including the downregulation
      of GluR1/GluR2 and NR2A/NR2B ratios in the hippocampus cytoplasm, a minute effect
      on the regulatory proteins CAMKII and PKA in the cerebral cortex, and increases
      in pGluR1, CAMKII, PKA and Reelin levels. Early GVG exposure was also associated
      with region specific regulation of monoamines, reduction in hippocampal DA, and
      enhancement of cortical NE levels. Age-dependent modified sociability and lack of
      preference for social interactions were observed in mice treated with GVG.
      Overall, early life exposure to GVG is expected to alter cortico-hippocampal axis
      connectivity and balance due to the different effects GVG has on key synaptic
      proteins in the associated brain regions, thus potentially causing behavioral
      impairment. 

PMID- 24462621
TI  - Tolfenamic acid downregulates BACE1 and protects against lead-induced
      upregulation of Alzheimer's disease related biomarkers.
AB  - Environmental exposure to lead (Pb) early in life results in a latent
      upregulation of genes and products associated with Alzheimer's disease (AD),
      particularly the plaque forming protein amyloid beta (Abeta). Furthermore,
      animals exposed to Pb as infants develop cognitive decline and memory impairments
      in old age. Studies from our lab demonstrated that tolfenamic acid lowers the
      levels of the amyloid beta precursor protein (APP) and its aggregative cleavage
      product Abeta by inducing the degradation of the transcription factor specificity
      protein 1 (Sp1). These changes were accompanied by cognitive improvement in
      transgenic APP knock-in mice. In this study, we examined the effects of
      tolfenamic acid on beta site APP cleaving enzyme 1 (BACE1) which is responsible
      for Abeta production and tested its ability to reverse Pb-induced upregulation in
      the amyloidogenic pathway. Mice were administered tolfenamic acid for one month
      and BACE1 gene expression as well as its enzymatic activity were analyzed in the
      cerebral cortex. Tolfenamic acid was also tested for its ability to reverse
      changes in Sp1, APP and Abeta that were upregulated by Pb in vitro.
      Differentiated SH-SY5Y neuroblastoma cells were either left unexposed, or
      sequentially exposed to Pb followed by tolfenamic acid. Our results show that
      tolfenamic acid reduced BACE1 gene expression and enzyme activity in mice. In
      neuroblastoma cells, Pb upregulated Sp1, APP and Abeta, while tolfenamic acid
      lowered their expression. These results along with previous data from our lab
      provide evidence that tolfenamic acid, a drug that has been used for decades for
      migraine, represents a candidate which can reduce the pathology of AD and may
      mitigate the damage of environmental risk factors associated with this disease. 

PMID- 24462622
TI  - Automated immunohistochemical method to quantify neuronal density in brain
      sections: application to neuronal loss after status epilepticus.
AB  - BACKGROUND: To study neurotoxic processes, it is necessary to quantify the number
      of neurons in a given brain structure and estimate neuronal loss. Neuronal
      densities can be estimated by immunohistochemical quantitation of a neuronal
      marker such as the protein NeuN. However, NeuN expression may vary, depending on
      certain pathophysiological conditions and bias such quantifications. NEW METHOD:
      We have developed a simple automatic quantification of neuronal densities in
      brain sections stained with DAPI and antibody to NeuN. This method determines the
      number of DAPI-positive nuclei also positive for NeuN in at least two adjacent
      sections within a Z-stack of optical sections. RESULTS: We tested this method in
      animals with induced status epilepticus (SE) a state of intractable persistent
      seizure that produces extensive neuronal injury. We found that SE significantly
      reduced neuronal density in the piriform cortex, the amygdala, the dorsal
      thalamus, the CA3 area of the hippocampus, the dentate gyrus and the hilus, but
      not in the somatosensory cortex or the CA1 area. SE resulted in increases in the
      total density of cellular nuclei within these brain structures, suggesting
      gliosis. COMPARISON WITH EXISTING METHODS: This automated method was more
      accurate than simply estimating the overall NeuN fluorescence intensity in the
      brain section, and as accurate, but less time-consuming, than manual cell counts.
      CONCLUSION: This method simplifies and accelerates the unbiased quantification of
      neuronal density. It can be easily applied to other models of brain injury and
      neurodegeneration, or used to screen the efficacy of neuroprotective treatments.

PMID- 24462623
TI  - Correlation of Giardia duodenalis assemblages with clinical and epidemiological
      data in Cuban children.
AB  - Giardia duodenalis is one of the most frequent intestinal parasitic infections in
      children worldwide. To date, eight main assemblages of G. duodenalis have been
      described, but only A and B genetic groups are known to infect humans. In Cuba,
      this parasite has most clinical impact on children. The aim of this investigation
      was genetic characterization of G. duodenalis isolated from children with
      giardiasis diagnosed at the Paediatric Hospital "William Soler" between 2010 and
      2011, and to compare the genetic results with clinical and epidemiological data.
      A total of 103 stool samples from 452 children were positive for G. duodenalis
      and co-infections with other parasites were noted in 5 cases. Assemblage
      identification was carried out by the amplification of a fragment of the
      triosephosphate isomerase (tpi) gene. Sub-assemblages of assemblage A (AI and
      AII) were identified by a nested PCR using the intergenic spacer (IGS) region of
      ribosomal deoxyribonucleic acid gene as a target. DNA from 90 of 103 (87.4%)
      samples was successfully amplified by PCR-tpi. The prevalence of assemblages A
      and B was 40% and 42%, respectively. Infections with both assemblages were
      reported in 16 cases. No associations between epidemiological information and
      assemblage was detected, but assemblage B was significantly (P<0.01) more
      frequently found in children with diarrhea, flatulence or abdominal pain than
      assemblage A. Sub-assemblage AII accounted for the majority of cases (86.5%). 

PMID- 24462624
TI  - Genotype circulation pattern of human respiratory syncytial virus in Iran.
AB  - In order to have information on the molecular epidemiology and genetic
      circulation pattern of human respiratory syncytial virus (HRSV) in Iran, we
      studied the genetic variability of both group A and B HRSV strains during seven
      consecutive years by sequencing the hypervariable C-terminal domain of G protein.
      A total of 485 children <2years of age who were negative for influenza viruses,
      screened for the presence of HRSV in this research. HRSV was detected in 94
      (19.38%) of the samples using nested RT-PCR. Group A viruses were isolated during
      each year, while group B viruses were isolated during 2009 and 2013. Phylogenetic
      analysis showed that all HRSV group A viruses belonged to three genotypes: GA1,
      GA2, GA5 and the group B viruses were in BA genotype. 

PMID- 24462625
TI  - Bisphosphonate treatment of bone loss in patients with inflammatory bowel
      disease.

PMID- 24462627
TI  - Hepatic encephalopathy involves interactions among the microbiota, gut, brain.

PMID- 24462626
TI  - Risks of serious infection or lymphoma with anti-tumor necrosis factor therapy
      for pediatric inflammatory bowel disease: a systematic review.
AB  - BACKGROUND & AIMS: Many physicians hesitate to recommend anti-tumor necrosis
      factor (TNF) therapy for pediatric patients with inflammatory bowel disease (IBD)
      because of concerns about risk of infection and cancer. We performed a systematic
      review to quantify the incidence of serious infection, lymphoma, and death among
      pediatric patients with IBD who received anti-TNF therapy. These values were
      compared with those expected from other treatments, from adults with IBD, and
      from the general pediatric population. METHODS: We searched MEDLINE, EMBASE, the
      Cochrane Collaboration, and Web of Knowledge for studies of infliximab therapy
      for children with ulcerative colitis or Crohn's disease, or adalimumab therapy
      for children with Crohn's disease. Standardized incidence ratios (SIRs) were
      calculated, comparing rates of infection and cancer among pediatric patients
      exposed to anti-TNF agents vs expected rates from pediatric patients not exposed
      to anti-TNF therapies or adult patients exposed to anti-TNF agents. Our analysis
      included 5528 patients with 9516 patient-years of follow-up evaluation (PYF).
      RESULTS: The rate of serious infections among pediatric patients treated with
      anti-TNF agents (352/10,000 PYF) was similar to that of pediatric patients who
      received immunomodulator monotherapy (333/10,000 PYF; SIR, 1.06; 95% confidence
      interval [CI], 0.83-1.36), but significantly lower than the expected rate for
      pediatric patients treated with steroids (730/10,000 PYF; SIR, 0.48; 95% CI, 0.40
      0.58) or adults treated with anti-TNF agents (654/10,000 PYF; SIR, 0.54; 95% CI,
      0.43-0.67). Five treatment-related deaths occurred (4 from sepsis and 1 from
      arrhythmia). Two patients developed lymphoma (2.1/10,000 PYF). This value was
      similar to the expected rate of lymphoid neoplasia in the entire pediatric
      population (5.8/100,000 PYF; SIR, 3.5; 95% CI, 0.35-19.6), and lower than the
      population of pediatric patients receiving thiopurine monotherapy (4.5/10,000
      PYF; SIR, 0.47; 95% CI, 0.03-6.44), and among adults treated with anti-TNF agents
      (6.1/10,000 PYF; SIR, 0.34; 95% CI, 0.04-1.51). CONCLUSIONS: Based on a
      systematic review, the risk of lymphoma was no greater among children with IBD
      who received anti-TNF therapy than those treated with other IBD therapies or
      adults treated with anti-TNF agents. The rate of serious infection was
      significantly lower among pediatric patients with IBD treated with anti-TNF
      agents than those treated with steroids, or adults with IBD who received anti-TNF
      therapy.

PMID- 24462628
TI  - Outcome of total hip arthroplasty for avascular necrosis of the femoral head in
      systemic lupus erythematosus.
AB  - This study evaluated the result of total hip arthroplasty (THA) for avascular
      necrosis of the femur head (AVNFH) in systemic lupus erythematosus (SLE)
      patients. Nineteen THAs were performed on 13 patients with SLE. The results of
      these patients were compared with the results of the control group (19 patients)
      who had THR due to AVNFH with none-SLE conditions. The Harris hip score increased
      from a preoperative average of 65.3 points to 94.9 at the most recent follow-up.
      In the control group, the mean HHS was 67.2 preoperatively and 96.1
      postoperatively at the last follow-up. No significant difference was found
      between SLE patients and non-SLE patients who underwent hip arthroplasty. In
      conclusion, THA is an acceptable treatment for achieving functional improvement
      in patients who had SLE and AVNFH.

PMID- 24462629
TI  - Workshop report: strategies for setting occupational exposure limits for
      engineered nanomaterials.
AB  - Occupational exposure limits (OELs) are important tools for managing worker
      exposures to chemicals; however, hazard data for many engineered nanomaterials
      (ENMs) are insufficient for deriving OELs by traditional methods. Technical
      challenges and questions about how best to measure worker exposures to ENMs also
      pose barriers to implementing OELs. New varieties of ENMs are being developed and
      introduced into commerce at a rapid pace, further compounding the issue of OEL
      development for ENMs. A Workshop on Strategies for Setting Occupational Exposure
      Limits for Engineered Nanomaterials, held in September 2012, provided an
      opportunity for occupational health experts from various stakeholder groups to
      discuss possible alternative approaches for setting OELs for ENMs and issues
      related to their implementation. This report summarizes the workshop proceedings
      and findings, identifies areas for additional research, and suggests potential
      avenues for further progress on this important topic. 

PMID- 24462630
TI  - 'It is the situation that makes it difficult': experiences of nursing students
      faced with a high-stakes drug calculation test.
AB  - Test anxiety affects the learning, performance and well-being of students, and it
      increases as the stakes get higher. Norwegian nursing students must pass a drug
      calculation test with a flawless performance if they are to qualify as nurses.
      The aim of the current study was to investigate the test anxiety experiences of
      students faced with such a high-stakes test. We used a mixed methods approach
      where the data were collected using a survey questionnaire and a focus group
      interview. In total, 203 freshman nursing students completed the questionnaire,
      six of whom also participated in the focus group interview. The survey results
      showed that 44.3% of the students reported high mathematics test anxiety in the
      months before the drug calculation test. More than 12% of the high-anxiety
      students reported a low mathematics self-concept. High and medium self-concept
      students also experienced high test anxiety. Our analysis of the focus group
      interview data confirmed that the high stakes of the test increased the test
      anxiety dramatically. 

PMID- 24462631
TI  - Effects of pre- and post-natal treatment with KRN633, an inhibitor of vascular
      endothelial growth factor receptor tyrosine kinase, on retinal vascular
      development and patterning in mice.
AB  - The impaired function of angiogenic factors, including vascular endothelial
      growth factor (VEGF), during pregnancy is associated with preeclampsia and
      intrauterine growth restriction. To determine how the attenuation of VEGF signals
      during retinal vascular development affects retinal vascular growth and patterns,
      we examined the effects of pre- and post-natal treatment of mice with KRN633, a
      VEGF receptor tyrosine kinase inhibitor, on retinal vascular development and
      structure. Delays in retinal vascular development were observed in the pups of
      mother mice that were treated daily with KRN633 (5 mg/kg/day) from embryonic day
      13.5 until the day of delivery. A more marked delay was seen in pups treated with
      the inhibitor (5 mg/kg/day) on the day of birth and on the following day. Pups
      treated postnatally with KRN633 showed abnormal retinal vascular patterns, such
      as highly dense capillary networks and decreased numbers of central arteries and
      veins. The high-density vascular networks in KRN633-treated pups showed a greater
      sensitivity to VEGF signaling inhibition than the normal vascular networks in
      vehicle-treated pups. Compared to vehicle-treated pups, more severe hypoxia and
      stronger VEGF mRNA expression were observed in avascular areas in KRN633-treated
      pups. These results suggest that a short-term loss of VEGF function at the
      earliest stages of vascular development suppresses vascular growth, leading to
      abnormal vascular patterning, at least in part via mechanisms involving VEGF in
      the mouse retina. 

PMID- 24462633
TI  - An exploratory model to illustrate the interrelationship between HIV, disability,
      and caregiving in southern Africa.
AB  - Increased caregiving burden and HIV-related disability have important
      implications for affected populations and health and social security systems in
      southern Africa. Based on a review of HIV, caregiving, and disability literature,
      and of existing disability models, the authors discuss the potential
      interrelationships between caregiving and disability in the context of HIV. They
      develop an exploratory model to illustrate these linkages. Co-existing
      experiences of disability and caregiving burden may lead to a vicious cycle of
      deteriorating well-being among affected households and place additional strain on
      social security systems. HIV may exacerbate this cycle at both a micro and a
      macro level. Research, policy, and practice should aim to provide more effective
      synergies between rehabilitation, HIV treatment, care and support, and household
      livelihood interventions. Particular attention should be paid to the ability of
      social systems to meet the specific needs of informal care providers with
      disability and their care recipients. 

PMID- 24462632
TI  - Integrin-dependent neutrophil migration in the injured mouse cornea.
AB  - As an early responder to an inflammatory stimulus, neutrophils (PMNs) must exit
      the vasculature and migrate through the extravascular tissue to the site of
      insult, which is often remote from the point of extravasation. Following a
      central epithelial corneal abrasion, PMNs recruited from the peripheral limbal
      vasculature migrate into the avascular corneal stroma. In vitro studies suggest
      PMN locomotion over 2-D surfaces is dependent on integrin binding while migration
      within 3-D matrices can be integrin-independent. Electron micrographs of injured
      mouse corneas show migrating PMNs make extensive surface contact not only with
      collagen fibrils in the extracellular matrix (ECM), but also keratocytes.
      Evidence supporting involvement of integrins in corneal inflammation has prompted
      research and development of integrin blocking agents for use as anti-inflammatory
      therapies. However, the role of integrin binding (cell-cell; cell-ECM) during
      stromal migration in the inflamed cornea has previously not been clearly defined.
      In this study in vivo time lapse imaging sequences provided the means to quantify
      cell motility while observing PMN interactions with keratocytes and other stromal
      components in the living eye. The relative contribution of beta1, beta2 and beta3
      integrins to PMN locomotion in the inflamed mouse cornea was investigated using
      blocking antibodies against the respective integrins. Of the 3 integrin families
      (beta1, beta2 and beta3) investigated for their potential role in PMN migration,
      only beta1 antibody blockade produced a significant, but partial, reduction in
      PMN motility. The preferential migration of PMNs along the keratocyte network was
      not affected by integrin blockade. Hence, the dominant mechanism for PMN motility
      within the corneal stroma appears to be integrin-independent as does the
      restriction of PMN migration paths to the keratocyte network. 

PMID- 24462634
TI  - State of the science: The efficacy of a multicomponent intervention for ART
      adherence among people living with HIV.
AB  - Incorrect or inconsistent adherence to antiretroviral therapy (ART) compromises
      the effectiveness of medications and the patient's chances of achieving viral
      suppression; near-perfect (>95%) compliance is required for both immediate and
      long-term clinical success. This report presents a systematic review of a
      multicomponent intervention to address adherence to ART and explores whether this
      intervention, when compared with standard care, resulted in improved ART
      adherence. Eleven randomized controlled trial studies published between 1999 and
      2008 were reviewed. Seven of these demonstrated a beneficial effect from
      multicomponent intervention, which primarily incorporated individual education
      and one to three additional interventions. Interventions targeting the
      improvement of the patient's medication management skills were particularly
      successful. However, because of incongruent results across studies, it could not
      be determined whether improved adherence extended to improved virologic or
      immunologic outcomes. There is a need for standardization and increased
      methodological rigor in the execution of adherence trials.

PMID- 24462635
TI  - Going the extra mile for retention and re-engagement in care: nurses make a
      difference.

PMID- 24462636
TI  - A phylogeographic evaluation of the Amolops mantzorum species group: cryptic
      species and plateau uplift.
AB  - Phylogeographic analysis brings organism phylogeny, regional geological/climatic
      history, and population demography together, and provides insights into species
      history and speciation. Using DNA sequence data from a mitochondrial marker
      (cytochrome b) and a nuclear marker (cmyc intron 2), we examined phylogeography
      of the Amolops mantzorum species group. We first constructed Bayesian and maximum
      likelihood gene trees and medium-joint networks for the recovered haplotypes, and
      estimated divergence time for each major lineage. Species boundaries were then
      delineated using the general mixed Yule-coalescent model (GMYC) and a Bayesian
      species-delimitation method (BP&P). Potential gene flow between putative species
      was also estimated using the isolation-with-migration model. Furthermore, species
      distribution modeling was used to probe linkage between climatic changes and
      speciation. Lastly, extended Bayesian skyline plotting was employed to reveal
      historical demography for each putative species. Our analyses clearly delimit
      nine species in the group, including four well-recognized species and five
      putative species, of which three are often listed as synonyms of A. mantzorum.
      The nominal species A. mantzorum may in fact include two cryptic species.
      Divergence-time estimates align the speciation events with the recent intense
      uplift of the Tibetan Plateau in the last 3.6 million years. The species
      distribution modeling also reveals different habitat preferences among species
      that are potentially linked to climatic changes associated with the uplift.
      Furthermore, three species sustained continuous population growth through the
      last glaciation, while others expanded only after the last glaciation. The
      eastern escarpment of Tibet is a biodiversity hotspot; its rich species
      diversity, unique topography, and well-established geological history provide an
      excellent system for evolutionary studies.

PMID- 24462637
TI  - Phylogenetic relationships of yellowjackets inferred from nine loci (Hymenoptera:
      Vespidae, Vespinae, Vespula and Dolichovespula).
AB  - Eusociality has arisen repeatedly and independently in the history of insects,
      often leading to evolutionary success and ecological dominance. Eusocial wasps of
      the genera Vespula and Dolichovespula, or yellowjackets, have developed advanced
      social traits in a relatively small number of species. The origin of traits such
      as effective paternity and colony size has been interpreted with reference to an
      established phylogenetic hypothesis that is based on phenotypic data, while the
      application of molecular evidence to phylogenetic analysis within yellowjackets
      has been limited. Here, we investigate the evolutionary history of yellowjackets
      on the basis of mitochondrial and nuclear markers (nuclear: 28S, EF1alpha, Pol
      II, and wg; mitochondrial: 12S, 16S, COI, COII, and Cytb). We use these data to
      test the monophyly of yellowjackets and species groups, and resolve species-level
      relationships within each genus using parsimony and Bayesian inference. Our
      results indicate that a yellowjacket clade is either weakly supported (parsimony)
      or rejected (Bayesian inference). However, the monophyly of each yellowjacket
      genus as well as species groups are strongly supported and concordant between
      methods. Our results agree with previous studies regarding the monophyly of the
      Vespula vulgaris group and the sister relationship between the V. rufa and V.
      squamosa groups. This suggests convergence of large colony size and high
      effective paternity in the vulgaris group and V. squamosa, or a single origin of
      both traits in the most recent common ancestor of all Vespula species and their
      evolutionary reversal in the rufa group. 

PMID- 24462638
TI  - Clinical management of epithelial ovarian cancer during pregnancy.
AB  - Epithelial ovarian cancer (EOC) in pregnancy is a rare situation. Due to its low
      incidence with a consecutive lack of clinical trials many questions regarding
      indication of different treatment approaches are unanswered. This article
      discusses the current literature to elaborate recommendations for the management
      of EOC during pregnancy. A literature search of diagnostic approaches and
      treatment strategies for EOC complicated by pregnancy was performed. We reviewed
      the available information with emphasis on surgery as well as chemotherapeutical
      treatment options. EOC in pregnancy is often diagnosed at early stage and no data
      support that concurrent pregnancy influences the growth rate or propensity for
      spread of EOC. Radical cytoreduction of all visible tumour followed by subsequent
      systemic chemotherapy is the standard treatment of EOC in most non-pregnant
      women. In pregnant women, however, chemotherapy as well as radical surgery should
      be avoided in the first trimester because of teratogenesis and high abortion
      rates. Besides induced abortion followed by classic management of EOC, pregnancy
      preserving surgery, followed by chemotherapy in the second or third trimester,
      timely delivery as well as neo-adjuvant chemotherapy with subsequent completing
      surgery appear to be viable treatment options. CONCLUSIONS: Since there is only
      very limited information regarding the optimal therapeutic approach to EOC during
      pregnancy, each case needs to be addressed individually. Treatment in specialised
      centres should be intended especially in this rare and challenging situation.

PMID- 24462639
TI  - Comprehensive geriatric assessment in the XXI century.

PMID- 24462640
TI  - Biotransformation of androgenic steroid mesterolone with Cunninghamella
      blakesleeana and Macrophomina phaseolina.
AB  - Fermentation of mesterolone (1) with Cunninghamella blakesleeana yielded four new
      metabolites, 1alpha-methyl-1beta,11beta,17beta-trihydroxy-5alpha-androstan-3-one
      (2), 1alpha-methyl-7alpha,11beta,17beta-trihydroxy-5alpha-androstan-3-one (3),
      1alpha-methyl-1beta,6alpha,17beta-trihydroxy-5alpha-androstan-3-one (4) and
      1alpha-methyl-1beta,11alpha,17beta-trihydroxy-5alpha-androstan-3-one (5), along
      with three known metabolites, 1alpha-methyl-11alpha,17beta-dihydroxy-5alpha
      androstan-3-one (6), 1alpha-methyl-6alpha,17beta-dihydroxy-5alpha-androstan-3-one
      (7) and 1alpha-methyl-7alpha,17beta-dihydroxy-5alpha-androstan-3-one (8).
      Biotransformation of 1 with Macrophomina phaseolina also yielded a new
      metabolite, 1alpha-methyl, 17beta-hydroxy-5alpha-androstan-3,6-dione (9). The
      isolated metabolites were subjected to various in vitro biological assays, such
      as anti-cancer, inhibition of alpha-glucosidase, and phosphodiesterase-5 enzymes
      and oxidative brust. However, no significant results were observed. This is the
      first report of biotransformation of 1 with C. blakesleeana and M. phaseolina. 

PMID- 24462641
TI  - Generating novel recombinant prokaryotic lectins with altered carbohydrate
      binding properties through mutagenesis of the PA-IL protein from Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Prokaryotic lectins offer significant advantages over eukaryotic
      lectins for the development of enhanced glycoselective tools. Amenability to
      recombinant expression in Escherichia coli simplifies their production and
      presents opportunities for further genetic manipulation to create novel
      recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate
      binding properties. This study explored the potential of the alpha-galactophilic
      PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the
      generation of novel RPLs. METHOD: Specific amino acid residues in the
      carbohydrate binding site of a recombinant PA-IL protein were randomly
      substituted by site-directed mutagenesis. The resulting expression clones were
      then functionally screened to identify clones expressing rPA-IL proteins with
      altered carbohydrate binding properties. RESULTS: This study generated RPLs
      exhibiting diverse carbohydrate binding activities including specificity and high
      affinity for beta-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by
      N-linked glycans on glycoprotein targets. Key amino acid substitutions were
      identified and linked with specific carbohydrate binding activities. Ultimately,
      the utility of these novel RPLs for glycoprotein analysis and for selective
      fractionation and isolation of glycoproteins and their glycoforms was
      demonstrated. CONCLUSIONS: The carbohydrate binding properties of the PA-IL
      protein can be significantly altered using site-directed mutagenesis strategies
      to generate novel RPLs with diverse carbohydrate binding properties. GENERAL
      SIGNIFICANCE: The novel RPLs reported would find a broad range of applications in
      glycobiology, diagnostics and in the analysis of biotherapeutics. The ability to
      readily produce these RPLs in gram quantities could enable them to find larger
      scale applications for glycoprotein or biotherapeutic purification.

PMID- 24462642
TI  - Present status and future challenges of electroencephalography- and magnetic
      resonance imaging-based monitoring in preclinical models of focal cerebral
      ischemia.
AB  - Animal models are useful tools for better understanding the mechanisms underlying
      neurological deterioration after an ischemic insult as well as subsequent
      evolution of changes and recovery of functions. In response to the updated
      requirements for preclinical investigations of stroke to include relevant
      functional measurement techniques and biomarker endpoints, we here review the
      state of knowledge on application of some translational electrophysiological and
      neuroimaging methods, and in particular, electroencephalography monitoring and
      magnetic resonance imaging in rodent models of ischemic stroke. This may lead to
      improvement of diagnostic methods and identification of new therapeutic targets,
      which would considerably advance the translational value of preclinical stroke
      research. 

PMID- 24462645
TI  - Unmet needs in the treatment of autoimmunity: from aspirin to stem cells.
AB  - As rheumatologic diseases became understood to be autoimmune in nature, the drugs
      used to treat this group of conditions has evolved from herbal or plant derived
      anti-inflammatory agents, such as salicylates, quinine and colchicine to the many
      recently approved biological response modifiers. These new drugs, especially the
      anti-tumor necrosis factor agents, have shown remarkable efficacy in autoimmune
      diseases, and there are new agents under investigation that will provide
      additional treatment options. In between, the world was introduced to cortisone
      and all of its derivatives, as chemical synthesis led to better, more efficacious
      drugs with lesser side effects. Disease modifying anti-rheumatic agents have
      actually been around since the first half of the 20th century, but only began to
      be used in the treatment of autoimmune diseases in the 1970s and 1980s. One
      advantage is that they have been invaluable in their ability to offer "steroid
      sparing" to decrease the adverse effects of steroids. Research over the past
      decade has resulted in a new class of drugs that influence cytokine regulatory
      pathways such as the Janus associated kinase inhibitors. The promise of
      personalized medicine now permeates current research into new pharmacological
      agents for the treatment of autoimmune disease. The new appreciation for the gene
      environment interaction in the pathogenesis of most diseases especially those as
      heterogeneous as autoimmune diseases, has led to our focus on targeted therapies.
      Add to that the new knowledge of epigenetics and how changes in DNA and histone
      structure affect expression of genes that can play a role in immune signaling,
      and we now have a new exciting frontier for cutting edge drug development. The
      history of treatment of autoimmune diseases is really only a little over a
      century, but so much has changed, leading to increasing lifespans and improved
      quality of life of those who suffer from these ailments. 

PMID- 24462644
TI  - Safe prescription recommendations for non steroidal anti-inflammatory drugs:
      consensus document ellaborated by nominated experts of three scientific
      associations (SER-SEC-AEG).
AB  - This article outlines key recommendations for the appropriate prescription of non
      steroidal anti-inflammatory drugs to patients with different musculoskeletal
      problems. These recommendations are based on current scientific evidence, and
      takes into consideration gastrointestinal and cardiovascular safety issues. The
      recommendations have been agreed on by experts from three scientific societies
      (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology
      [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi
      methodology. Areas that have been taken into account encompass: efficiency,
      cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory
      bowel disease, anemia, post-operative pain, and prevention strategies. We propose
      a patient management algorithm that summarizes the main aspects of the
      recommendations. 

PMID- 24462643
TI  - Channelopathies and dendritic dysfunction in fragile X syndrome.
AB  - Dendritic spine abnormalities and the metabotropic glutamate receptor theory put
      the focus squarely on synapses and protein synthesis as the cellular locus of
      fragile X syndrome. Synapses however, are only partly responsible for information
      processing in neuronal networks. Neurotransmitter triggered excitatory
      postsynaptic potentials (EPSPs) are shaped and integrated by dendritic voltage
      gated ion channels. These EPSPs, and in some cases the resultant dendritic
      spikes, are further modified by dendritic voltage-gated ion channels as they
      propagate to the soma. If the resultant somatic depolarization is large enough,
      action potential(s) will be triggered and propagate both orthodromically down the
      axon, where it may trigger neurotransmitter release, and antidromically back into
      the dendritic tree, where it can activate and modify dendritic voltage-gated and
      receptor activated ion channels. Several channelopathies, both soma-dendritic (L
      type calcium channels, Slack potassium channels, h-channels, A-type potassium
      channels) and axo-somatic (BK channels and delayed rectifier potassium channels)
      were identified in the fmr1-/y mouse model of fragile X syndrome. Pathological
      function of these channels will strongly influence the excitability of individual
      neurons as well as overall network function. In this chapter we discuss the role
      of voltage-gated ion channels in neuronal processing and describe how identified
      channelopathies in models of fragile X syndrome may play a role in dendritic
      pathophysiology.

PMID- 24462647
TI  - Steroid signaling: ligand-binding promiscuity, molecular symmetry, and the need
      for gating.
AB  - Steroid/sterol-binding receptors and enzymes are remarkably promiscuous in the
      range of ligands they can bind to and, in the case of enzymes, modify - raising
      the question of how specific receptor activation is achieved in vivo. Estrogen
      receptors (ER) are modulated by 27-hydroxycholesterol and 5alpha-androstane
      3beta,17beta-diol (Adiol), in addition to estradiol (E2), and respond to diverse
      small molecules such as bisphenol A. Steroid-modifying enzymes are also highly
      promiscuous in ligand binding and metabolism. The specificity problem is
      compounded by the fact that the steroid core (hydrogenated cyclopentophenanthrene
      ring system) has several planes of symmetry. Ligand binding can be in symmetrical
      East-West (rotation) and North-South (inversion) orientations. Hydroxysteroid
      dehydrogenases (HSDs) can modify symmetrical 7 and 11, also 3 and 17/20,
      positions, exemplified here by yeast 3alpha,20beta-HSD and mammalian 11beta-HSD
      and 17beta-HSD enzymes. Faced with promiscuity and symmetry, other strategies are
      clearly necessary to promote signaling selectivity in vivo. Gating regulates
      hormone access via enzymes that preferentially inactivate (or activate) a
      subclass of ligands, thereby governing which ligands gain receptor access -
      exemplified by 11beta-HSD gating cortisol access to the mineralocorticoid
      receptor, and P450 CYP7B1 gating Adiol access to ER. Counter-intuitively, the
      specificity of steroid/sterol action is achieved not by intrinsic binding
      selectivity but by the combination of local metabolism and binding affinity.

PMID- 24462646
TI  - Induction of autophagy biomarker BNIP3 requires a JAK2/STAT3 and MT1-MMP
      signaling interplay in Concanavalin-A-activated U87 glioblastoma cells.
AB  - Plant lectins have been considered as possible anti-tumor drugs because of their
      property to induce autophagic cell death. Given that expression of membrane type
      1 matrix metalloproteinase (MT1-MMP) has been found to regulate expression of the
      autophagy biomarker Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3), we
      sought to investigate possible signaling interplay mechanisms between MT1-MMP and
      BNIP3 in Concanavalin-A (ConA) lectin-activated U87 glioblastoma cells. ConA
      induced acidic vacuole organelle formation as well as BNIP3 and MT1-MMP gene and
      protein expressions, whereas only BNIP3 expression was dose-dependently inhibited
      by the JAK2 tyrosine kinase inhibitor AG490 suggesting a requirement for some
      STAT-mediated signaling. Gene silencing of MT1-MMP and of STAT3 abrogated ConA
      induced STAT3 phosphorylation and BNIP3 expression. Correlative analysis shows
      that STAT3 signaling events occur downstream from MT1-MMP induction.
      Overexpression of a full length MT1-MMP recombinant protein led to increased
      BNIP3 gene and protein expressions. The cytoplasmic domain of MT1-MMP was also
      found necessary for transducing STAT3 phosphorylation. Among JAK1, JAK2, JAK3,
      and TYK2, only JAK2 gene silencing abrogated ConA's effects on MT1-MMP and BNIP3
      gene and protein expressions. Our study elucidates how MT1-MMP signals autophagy,
      a process which could contribute to the chemoresistance phenotype in brain cancer
      cells. 

PMID- 24462648
TI  - Synthesis of novel 16-spiro steroids: 7-(Aryl)tetrahydro-1H-pyrrolo[1,2
      c][1,3]thiazolo estrone hybrid heterocycles.
AB  - The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the
      reaction of isatins or acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic
      acid to various exocyclic dipolarophiles synthesized from estrone afforded a
      library of novel C-16 spiro oxindole or acenaphthylene-1-one - 7-(aryl)tetrahydro
      1H-pyrrolo[1,2-c][1,3]thiazole - estrone hybrid heterocycles. These reactions
      occur regio- and stereo-selectively affording a single isomer of the spiro
      estrones in excellent yields with the formation of two C-C and one C-N bonds
      along with the generation of four new contiguous stereo-centers in a single step.

PMID- 24462649
TI  - Six months chronic toxicological evaluation of naringin in Sprague-Dawley rats.
AB  - Naringin is a flavonoid showing variable pharmacological properties and is
      distributed ubiquitously in plant foods. There is a paucity of reported data
      regarding its safety profile. In the present study, chronic toxicity studies of
      naringin was designed and conducted by oral gavage at doses of 0, 50, 250 and
      1250 mg/kg in Sprague-Dawley (SD) rats for six months followed by 1-month
      recovery period. During the 6-month treatment period and one month recovery
      period, no mortality and toxicologically significant changes in clinical signs,
      opthalmoscopic examination, hematology, clinical biochemistry, serumsexhormone,
      macroscopic findings, organ weights and histopathological examination were noted
      and attributed to naringin administration. Although consecutive and/or isolated
      periods of significant body weights and food consumption decreases were relevant
      to naringin administration, they were not considered toxicologically significant.
      In addition, slight, non-pathological and reversible hair loss was noted during
      the 6-month treatment period and considered as a kind of change possibly relevant
      to naringin administration; however, it was not considered adverse change and to
      be of toxicological significance. Based on the results of this study, the no
      observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250
      mg/kg/day when administered orally for 6 consecutive months.

PMID- 24462650
TI  - Regrown first rib in patients with recurrent thoracic outlet syndrome.
AB  - BACKGROUND: Recurrent symptoms of thoracic outlet syndrome (TOS) after first rib
      resection have varying etiologies. Regrowth of a first rib is a rare event.
      Recurrent symptoms in the presence of a regrown rib strongly suggest a causal
      relationship. We report our experience with recurrent symptoms of TOS and regrown
      first ribs. METHODS: We identified patients with recurrent TOS symptoms and
      regrown first ribs presented between 1995 and 2012. Details regarding their
      presentation, evaluation, and treatment were gathered. RESULTS: Eight patients (6
      women and 2 men) presenting with recurrent TOS symptoms and regrown first ribs
      underwent 10 decompression surgeries. Prior surgeries included supraclavicular
      first rib resection (5), transaxillary first rib resection (5), scalenectomy (5),
      cervical rib resection (1). The average period between initial surgery and
      reoperation was 4.7 years. Average age at current presentation was 40.8 years
      (range 29-52). All patients (8) represented with neurogenic symptoms and 1
      patient with concomitant venous TOS symptoms. Presenting symptoms included pain
      (8), numbness and tingling (7), weakness (6), headache (2), and venous congestion
      (3). Initial treatment included physical therapy in all. Preoperative assessment
      included chest X-rays (8), magnetic resonance imaging (7), electrodiagnostic
      studies (8), venography (2), and anterior scalene muscle block (2). Surgical
      approach included transaxillary resection of the regrown first rib (10),
      neurolysis of brachial plexus (10), scalenectomy (5), and lysis of subclavian
      vein (1). After an average follow-up of 10.8 months, resolution of symptoms
      included 4 complete and 4 partial. CONCLUSIONS: Regrowth of the first rib is a
      rare event. There is a concordance between a regrown rib and TOS symptoms.
      Patients presenting with recurrent TOS symptoms and a regrown first rib have a
      high probability of improvement with resection of the regrown rib.

PMID- 24462651
TI  - Preoperative anemia and its management.
AB  - The WHO defines anemia as 13 g/dl in males, 12 g/dl in non-pregnant women, and 11
      g/dl in pregnant women. Anemia is prevalent in various patient populations. The
      detrimental affect of anemia is present in all of this population of patients.
      Preoperative anemia is associated with perioperative increased perioperative
      morbidity and mortality and increased risks of blood transfusion, a standardized
      approach for the detection, evaluation, and management of anemia is needed.

PMID- 24462652
TI  - Acute myocardial infarction associated with blood transfusion: case report and
      literature review.
AB  - A 62-year old patient with a history of chronic anemia associated with
      malabsorption secondary to short gut syndrome, experienced acute chest pain the
      second hour after the transfusion of a crossmatch-compatible erythrocyte
      suspension. His electrocardiogram (ECG) revealed widespread ST-segment
      depressions and he had an elevated troponin level. Laboratory findings and
      physical examination did not indicate the presence of immunological or non
      immunological blood transfusion reactions. Cardiac catheterization was performed
      and showed angiographically non-obstructive, atherosclerotic plaques and the
      absence of vasospasm or thrombus formation. Following antiischemic therapy his
      symptoms resolved completely. The ECG obtained 24 hours after the emergence of
      chest pain demonstrated normal sinus rhythm with no ST-T wave changes. We present
      a rare case of acute myocardial infarction induced following a blood transfusion.
      To the best of our knowledge, a few cases of acute myocardial infarction
      associated with blood transfusion have been formally recorded in the medical
      literature and the clinical experience regarding such cases is indeed quite
      limited. The present case is reviewed in the context of the relevant literature
      as a practical resource for clinical practice. 

PMID- 24462653
TI  - Curcumin as a modulator of oxidative stress during storage: a study on plasma.
AB  - BACKGROUND: Plasma reflects the situations of oxidative stress in blood. Curcumin
      as an additive in storage solutions is not explored. MATERIALS AND METHODS: Blood
      was drawn from male Wistar rats (4 months old) and stored over a period of 20
      days at 4  degrees C in CPDA-1. Plasma was isolated from stored blood at regular
      intervals. Oxidative stress markers were analyzed in controls and experimental
      samples (with curcumin 10mM, 30 mM and 60mM). RESULTS: Antioxidant enzymes and
      sulfhydryls ameliorated, while TBARS and protein carbonyls reduced in curcumin
      samples. However, curcumin could not protect the susceptible groups in proteins
      thereby leading to dityrosine linkages (AOPP). CONCLUSION: Curcumin was
      beneficial at higher concentrations as it reduced oxidative stress, therefore
      paving way for the further studies on curcumin as a component in storage
      solutions.

PMID- 24462654
TI  - Anaphylaxis related with positively charged white-cell reduction filters.
AB  - Allergic reactions related to blood transfusion frequently occur and most of them
      are mild reactions such as urticaria, erythema, pruritus and flushing. More
      severe and life threatening allergic reactions such as anaphylactic shock rarely
      occur. Application of white cell reduction filters during transfusions may
      prevent alloimmunization, febrile nonhemolytic reactions and transmission of
      intracellular infectious agents. Despite their beneficial effects, white-cell
      reduction filters may cause allergic reactions. In this article we present three
      patients who had anaphylactic reactions during blood transfusion with positively
      charged leucocyte filters. 

PMID- 24462655
TI  - Does ictal whistling help to lateralise.

PMID- 24462656
TI  - Assessment of a modified 4T scoring system for heparin-induced thrombocytopenia
      in critically ill patients.
AB  - PURPOSE: The purpose of the study is to determine if a modified 4T (m4T) scoring
      system, which omits clinical evaluation of other thrombocytopenic etiologies, is
      different from the 4T scoring system's probability to predict a positive heparin
      induced thrombocytopenia (HIT) laboratory test in the intensive care unit.
      MATERIALS AND METHODS: This is a single-centered retrospective analysis of
      critically ill adults who had an enzyme-linked immunosorbent assay antiplatelet
      factor 4 antibody (ELISA anti-PF4 Ab) ordered. Patients were identified as HIT
      positive (optical density, >=0.40) or HIT negative (optical density, <0.40) based
      on the ELISA anti-PF4 Ab. Both 4T and m4T scores were calculated, and the
      diagnostic accuracy was compared using paired receiver operating characteristic
      curves. RESULTS: A total of 1487 adult intensive care unit patients with an ELISA
      anti-PF4 Ab ordered between January 2007 and December 2009 were eligible for
      study enrollment. Application of exclusion criteria and random selection yielded
      a total of 232 patients included for analysis (58 HIT-positive and 174 HIT
      negative patients). The area under the curve for the 4T and m4T scores were 0.683
      (95% confidence interval, 0.604-0.762) and 0.680 (95% confidence interval, 0.600
      0.759), respectively (P=.065). CONCLUSION: This study does not show a difference
      in the probability of the m4T and 4T scoring systems to predict a positive ELISA
      anti-PF4 Ab test in the critically ill patient population. Further prospective
      studies are needed to validate the m4T scoring system.

PMID- 24462657
TI  - Echocardiography-guided left ventricular lead placement for cardiac
      resynchronization therapy in ischemic vs nonischemic cardiomyopathy patients.
AB  - BACKGROUND: Echocardiography-guided (EG) left ventricular (LV) lead placement at
      the site of latest mechanical activation improves outcome in heart failure (HF)
      patients receiving a cardiac resynchronization therapy (CRT)-defibrillator (CRT
      D). OBJECTIVE: The purpose of this study was to examine the effect of a strategy
      of EG LV lead placement in each of ischemic (ICM) vs nonischemic (NICM)
      cardiomyopathy patients. METHODS: Patients enrolled in the Speckle Tracking
      Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective,
      randomized trial who were treated with a CRT-D device (108 EG strategy and 75
      routine strategy) were followed to the end-points of death, appropriate CRT-D
      therapy, or HF hospitalization. RESULTS: Of the patients enrolled in STARTER, 115
      had ICM and 68 had NICM. Over mean follow-up of 3.7 +/- 2.1 years, 62 patients
      died, 40 received appropriate CRT-D therapy, and 67 had HF hospitalizations.
      Compared to NICM patients, patients with ICM had worse survival (P = .0003),
      worse survival free from implantable cardioverter-defibrillator therapy (P =
      .004), and survival free from HF hospitalization (P = .0001). A strategy of EG LV
      lead placement improved the outcome of CRT-D therapy-free survival primarily in
      ICM patients and the outcome of HF hospitalization-free survival in both ICM and
      NICM patients. Achieving LV resynchronization was most critical in ICM patients
      in whom arrhythmic and HF outcomes improve with resynchronization to levels
      comparable to those of NICM patients. CONCLUSION: A strategy of EG LV lead
      placement improves HF-free survival equally in ICM and NICM patients and CRT-D
      therapy-free survival more favorably in ICM patients to levels comparable to
      those of NICM patients.

PMID- 24462658
TI  - Diagnosing Aleutian mink disease infection by a new fully automated ELISA or by
      counter current immunoelectrophoresis: a comparison of sensitivity and
      specificity.
AB  - Aleutian disease (AD) is a severe disease characterized by hypergammaglobulinemia
      causing multiple symptoms such as acute renal failure, arteritis, reduced
      reproductive performance and pneumonia in mink. AD is caused by the parvovirus
      Aleutian mink disease virus (ADV) and diagnosed primarily based on ADV serology
      sometimes supplemented by organ PCR analysis. In Denmark, approximately 3.5-4
      million serum samples are tested every year for the presence of anti ADV
      antibodies as part of a national eradication program. The present study compares
      the diagnostic performance of the two most commonly used assays for serological
      screening for Aleutian disease: counter current immunoelectrophoresis (CIEP) and
      ELISA. In total, 3810 mink were sampled in doublets and analyzed by CIEP and a
      newly developed fully automated ELISA. The results show that the two assays have
      a comparable diagnostic performance with the ELISA having a higher sensitivity
      but lower specificity than the CIEP assay. The ELISA has been approved by the
      Danish authorities for diagnosing Aleutian disease in mink. 

PMID- 24462659
TI  - Arsenic exposure and bladder cancer: quantitative assessment of studies in human
      populations to detect risks at low doses.
AB  - While exposures to high levels of arsenic in drinking water are associated with
      excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels
      (e.g., <100-200 ug/L) generally are not. Lack of significant associations may
      result from methodological issues (e.g., inadequate statistical power, exposure
      misclassification), or a different dose-response relationship at low exposures,
      possibly associated with a toxicological mode of action that requires a
      sufficient dose for increased tumor formation. The extent to which bladder cancer
      risk for low-level arsenic exposure can be statistically measured by
      epidemiological studies was examined using an updated meta-analysis of bladder
      cancer risk with data from two new publications. The summary relative risk
      estimate (SRRE) for all nine studies was elevated slightly, but not significantly
      (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The
      SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the
      SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97
      1.44, p-H=0.034). The SRRE was statistically significantly lower than relative
      risks predicted for never smokers in the United States based on linear
      extrapolation of risks from higher doses in southwest Taiwan to arsenic water
      exposures >10 ug/L for more than one-third of a lifetime. By contrast, for all
      study subjects, relative risks predicted for one-half of lifetime exposure to 50
      ug/L were just above the upper 95% CI on the SRRE. Thus, results from low
      exposure studies, particularly for never smokers, were statistically inconsistent
      with predicted risk based on high-dose extrapolation. Additional studies that
      better characterize tobacco use and stratify analyses of arsenic and bladder
      cancer by smoking status are necessary to further examine risks of arsenic
      exposure for smokers.

PMID- 24462660
TI  - Pharmacological and biochemical studies on the venom of a clinically important
      viper snake (Echis carinatus) of Pakistan.
AB  - Echis carinatus (saw-scaled viper) has been the major culprit responsible for
      serious envenomation casualties throughout the subcontinent. The present study
      describes the electrophoretic and zymographic characterization of E. carinatus
      venom and its effect on mammalian smooth muscle. Crude venom showed the presence
      of disintegrin, PLA2, C-type lectin/lectin-like components, CRISP, Serine
      protease, l-amino acid oxidase and very high concentrations of SVMPs. E.
      carinatus venom (1, 10, 30, 50, 100 MUg/ml) inhibited the active tension/force of
      muscle contraction in a time and concentration dependent manner. The observed
      effects abolished when the venom was heated at 100  degrees C for 5 min. However,
      a decrease in bath temperature from 37  degrees C to 26  degrees C or an increase
      in CaCl2 concentration to 5 mM did not prevent the inhibition of contractile
      activity. The contractile response elicited by exogenous application of 50 mM KCl
      and 1 MUM acetylcholine (ACh) was also significantly inhibited by all venom
      concentrations. Prior administration of commercially available polyvalent anti
      venom partially neutralized and prevented the effect of E. carinatus venom
      whereas addition of anti-venom at t50 failed to reverse the inhibitory effect.
      Studies on isolated intestinal muscle indicate involvement of myotoxic and
      apoptotic components in E. carinatus venom for irreversible damage to muscle
      tissue. 

PMID- 24462661
TI  - Rapid short term and gradual permanent cardiotoxic effects of vertebrate toxins
      from Chironex fleckeri (Australian box jellyfish) venom.
AB  - The vertebrate cardiotoxic components of the venom produced by the Australian box
      jellyfish, Chironex fleckeri, have not previously been isolated. We have
      uncovered for the first time, three distinct cytotoxic crude fractions from
      within the vertebrate cardiotoxic peak of C. fleckeri venom by monitoring
      viability of human muscle cells with an impedance based assay (ACEA xCELLigence
      system) measuring cell detachment as cytotoxicity which was correlated with a
      reduction in cell metabolism using a cell proliferation (MTS) assay. When the
      effects of the venom components on human cardiomyocytes and human skeletal muscle
      cells were compared, two fractions were found to specifically affect
      cardiomyocytes with distinct temporal profiles (labelled Crude Toxic Fractions
      (CTF), alpha and beta). A third fraction (CTF-gamma) was toxic to both muscle
      cell types and therefore not cardio specific. The vertebrate, cardio specific CTF
      alpha and CTF-beta, presented distinct activities; CTF-alpha caused rapid but
      short term cell detachment and reduction in cell metabolism with enhanced
      activity at lower concentrations than CTF-beta. This activity was not permanent,
      with cell reattachment and subsequent increased metabolism of heart muscle cells
      observed when exposed to all but the highest concentrations of CTF-alpha tested.
      The cytotoxic effect of CTF-beta took twice as long to act on the cells compared
      to CTF-alpha, however, the activity was permanent. Furthermore, we showed that
      the two fractions combined have a synergistic effect causing a much stronger and
      faster cell detachment (death) when combined than the sum of the individual
      effects of each toxin. These data presented here improves the current
      understanding of the toxic mechanisms of the Australian box jellyfish, C.
      fleckeri, and provides a basis for in vivo research of these newly isolated toxic
      fractions. 

PMID- 24462662
TI  - The use of botulinum toxin in the treatment of the consequences of bruxism on
      cervical spine musculature.
AB  - Hypertonia and hyperactivity of masticatory muscles are involved in pain and
      contractions of the cervical spine musculature, but their pathophysiology remains
      nonetheless unknown and its treatment far to be codified. In this study, 8
      patients, showing disabling posterior neck muscle contractures linked with
      bruxism were prospectively treated and followed for an average 15 months period,
      after having received Injections of botulinum toxin A essentially in masticatory
      muscles. Injections were made every 3 months, varying from 10 to 100 U Botox* by
      muscles, without administrating more than 300 U Botox* in the same patient. The
      angle of cervical lordosis were calculated on lateral sitting radiographs in
      neutral position, good results being considered to be achieved in the case of a 2
      point diminution of VAS score as well as at least a 5 degrees  positive gain in
      the curve. 7 patients out of 8 showed a real improvement in their symptoms after
      an average of 3 injections, showing a decrease of 4.5 points on the VAS score and
      an average increment of 15 degrees  in cervical lordosis. Although the follow-up
      period of patients was relatively short and the sample quite small, the general
      impression, confirmed by the patients' experience, seems to suggest a potential
      place for the use of botulinum toxin amongst the array of treatments which can be
      offered in certain selected cases which associate bruxism and posterior cervical
      contractions. 

PMID- 24462664
TI  - Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: development of a
      [3.3.0]-based series and other piperidine bioisosteres.
AB  - This Letter describes the development and SAR of a novel series of GlyT1
      inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign,
      which provided intellectual property position. Members within this new [3.3.0]
      based series displayed excellent GlyT1 potency, selectivity, free fraction, and
      modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed,
      within this novel series and a number of other piperidine bioisosteric cores.

PMID- 24462663
TI  - Mutation in osteoactivin decreases bone formation in vivo and osteoblast
      differentiation in vitro.
AB  - We have previously identified osteoactivin (OA), encoded by Gpnmb, as an
      osteogenic factor that stimulates osteoblast differentiation in vitro. To
      elucidate the importance of OA in osteogenesis, we characterized the skeletal
      phenotype of a mouse model, DBA/2J (D2J) with a loss-of-function mutation in
      Gpnmb. Microtomography of D2J mice showed decreased trabecular mass, compared to
      that in wild-type mice [DBA/2J-Gpnmb(+)/SjJ (D2J/Gpnmb(+))]. Serum analysis
      showed decreases in OA and the bone-formation markers alkaline phosphatase and
      osteocalcin in D2J mice. Although D2J mice showed decreased osteoid and
      mineralization surfaces, their osteoblasts were increased in number, compared to
      D2J/Gpnmb(+) mice. We then examined the ability of D2J osteoblasts to
      differentiate in culture, where their differentiation and function were
      decreased, as evidenced by low alkaline phosphatase activity and matrix
      mineralization. Quantitative RT-PCR analyses confirmed the decreased expression
      of differentiation markers in D2J osteoblasts. In vitro, D2J osteoblasts
      proliferated and survived significantly less, compared to D2J/Gpnmb(+)
      osteoblasts. Next, we investigated whether mutant OA protein induces endoplasmic
      reticulum stress in D2J osteoblasts. Neither endoplasmic reticulum stress markers
      nor endoplasmic reticulum ultrastructure were altered in D2J osteoblasts.
      Finally, we assessed underlying mechanisms that might alter proliferation of D2J
      osteoblasts. Interestingly, TGF-beta receptors and Smad-2/3 phosphorylation were
      up-regulated in D2J osteoblasts, suggesting that OA contributes to TGF-beta
      signaling. These data confirm the anabolic role of OA in postnatal bone
      formation. 

PMID- 24462665
TI  - Discovery of novel indazole derivatives as dual angiotensin II antagonists and
      partial PPARgamma agonists.
AB  - Identification of indazole derivatives acting as dual angiotensin II type 1 (AT1)
      receptor antagonists and partial peroxisome proliferator-activated receptor-gamma
      (PPARgamma) agonists is described. Starting from Telmisartan, we previously
      described that indole derivatives were very potent partial PPARgamma agonists
      with loss of AT1 receptor antagonist activity. Design, synthesis and evaluation
      of new central scaffolds led us to the discovery of pyrrazolopyridine then
      indazole derivatives provided novel series possessing the desired dual activity.
      Among the new compounds, 38 was identified as a potent AT1 receptor antagonist
      (IC50=0.006 MUM) and partial PPARgamma agonist (EC50=0.25 MUM, 40% max) with good
      oral bioavailability in rat. The dual pharmacology of compound 38 was
      demonstrated in two preclinical models of hypertension (SHR) and insulin
      resistance (Zucker fa/fa rat).

PMID- 24462666
TI  - Discovery of 6-aryl-azabenzimidazoles that inhibit the TBK1/IKK-epsilon kinases.
AB  - The discovery and optimization of a series of 6-aryl-azabenzimidazole inhibitors
      of TBK1 and IKK-epsilon is described. Various internal azabenzimidazole leads and
      reported TBK1/IKK-epsilon inhibitors were docked into a TBK1 homology model. The
      resulting overlays inspired a focused screen of 6-substituted azabenzimidazoles
      against TBK1/IKK-epsilon. This screen resulted in initial hit compound 3. The
      TBK1/IKK-epsilon enzyme and cell potency of this compound was further improved
      using structure guided drug design. Systematic exploration of the C6 aryl group
      led to compound 19, a potent inhibitor of TBK1 with selectivity against cell
      cycle kinases CDK2 and Aurora B. Further elaboration and optimization gave
      compound 25, a single digit nM inhibitor of TBK1. These compounds may serve as in
      vitro probes to evaluate TBK1/IKK-epsilon as an oncology target. 

PMID- 24462667
TI  - New class of azaheptapyridine FPT inhibitors as potential cancer therapy agents.
AB  - Tertiary hydroxyl class of C-imidazole bridgehead azaheptapyridine FPT inhibitors
      were prepared in an attempt to block in vivo oxidation of secondary hydroxyl
      series. One representative compound 5a exhibited potent enzyme (IC50=1.4 nM) and
      cellular activities (soft agar IC50=1.3 nM) with excellent oral pharmacokinetic
      profiles in rats, mice, monkeys and dogs. The in vivo study in wap-ras TG mouse
      models showed dose dependent tumor growth inhibition and regression.

PMID- 24462668
TI  - The reducing end sequence of wheat endosperm cell wall arabinoxylans.
AB  - Walls from wheat (Triticum aestivum L.) endosperm are composed primarily of
      hetero-(arabino)xylans (AXs) (70%) and (1->3)(1->4)-beta-D-glucans (20%) with
      minor amounts of cellulose and heteromannans (2% each). To understand the
      differential solubility properties of the AXs, as well as aspects of their
      biosynthesis, we are sequencing the xylan backbone and examining the reducing end
      (RE) sequence(s) of wheat (monocot) AXs. A previous study of grass AXs
      (switchgrass, rice, Brachypodium, Miscanthus and foxtail millet) concluded that
      grasses lacked the comparable RE glycosyl sequence (4-beta-D-Xylp-(1->4)-beta-D
      Xylp-(1->3)-alpha-L-Rhap-(1->2)-alpha-D-GalpA-(1->4)-D-Xylp) found in dicots and
      gymnosperms but the actual RE sequence was not determined. Here we report the
      isolation and structural characterisation of the RE oligosaccharide sequence(s)
      of wheat endosperm cell wall AXs. Walls were isolated as an alcohol-insoluble
      residue (AIR) and sequentially extracted with hot water (W-sol Fr) and 1M KOH
      containing 1% NaBH4 (KOH-sol Fr). Detailed structural analysis of the RE
      oligosaccharides was performed using a combination of methylation analysis, MALDI
      TOF-MS, ESI-QTOF-MS, ESI-MS(n) and enzymic analysis. Analysis of RE
      oligosaccharides, both 2AB labelled (from W-sol Fr) and glycosyl-alditol (from
      KOH-sol Fr), revealed that the RE glycosyl sequence of wheat endosperm AX
      comprises a linear (1->4)-beta-D-Xylp backbone which may be mono-substituted with
      either an alpha-L-Araf residue at the reducing end beta-D-Xylp residue and/or
      penultimate RE beta-D-Xyl residue; beta-D-Xylp-(1->4)-[alpha-L-Araf-(1->3)](+/-)
      beta-D-Xylp-(1->4)-[alpha-L-Araf-(1->3)](+/-)-beta-D-Xylp and/or an alpha-D-GlcpA
      residue at the reducing end beta-D-Xylp residue; beta-D-Xylp-(1->4)-[alpha-L-Araf
      (1->3)](+/-)-beta-D-Xylp-(1->4)-[alpha-D-GlcAp-(1->2)]-beta-D-Xylp. Thus, wheat
      endosperm AX backbones lacks the RE sequence found in dicot and gymnosperm
      xylans; a finding consistent with previous reports from other grass species.

PMID- 24462669
TI  - Synthesis of bis-cellobiose and bis-glucose derivatives of azacrown macrocycles
      as hosts in complexes with acetylsalicylic acid and 4-acetamidophenol.
AB  - Two new C2 symmetric bis-cellobiose and bis-glucose azacrown derivatives were
      prepared according to the one-step procedure using azacrown ethers and
      azidosaccharides. Their complexes with aspirin and paracetamol were studied with
      the use of proton NMR spectroscopy. It was found that these pseudocryptands bind
      aspirin and paracetamol but each one in a different manner. 

PMID- 24462670
TI  - Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton
      regulation in hydrocephalus pathology.
AB  - Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi
      ciliated ependymal cells through the ventricular system of the vertebrate brain.
      Defects in the ependymal layer functionality are a common cause of hydrocephalus.
      N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of
      actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with
      neural tube and cardiac abnormalities. To shed light on the role of N-WASP in
      mouse brain development, we generated N-WASP conditional knockout mouse model N
      WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios
      but exhibited reduced growth characteristics compared to their littermates
      containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed
      cranial deformities due to excessive CSF accumulation and did not survive past
      weaning. Coronal brain sections of these animals revealed dilated lateral
      ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced
      thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N
      cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to
      normal morphology in the wild-type controls. Moreover, scanning electron
      microscopy and immunofluorescence analyses of coronal brain sections with anti
      acetylated tubulin antibodies revealed the absence of cilia in ventricular walls
      of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not
      lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which
      have been previously implicated in hydrocephalus pathology. Taken together, our
      results suggest that N-WASP plays a critical role in normal brain development and
      implicate actin cytoskeleton regulation as a vulnerable axis frequently
      deregulated in hydrocephalus. 

PMID- 24462671
TI  - Association between adiponectin and cartilage degradation in human
      osteoarthritis.
AB  - OBJECTIVE: Conflicting findings raise questions about the role of adiponectin in
      osteoarthritis (OA). The current study aimed to investigate in OA patients the
      association between the production of adiponectin and the grade of cartilage
      destruction, and to provide functional evidence for a potential role of
      adiponectin in OA. DESIGN: The expression of adiponectin was examined by
      immunohistochemistry in cartilage obtained from healthy individuals (n = 2; ages
      56 and 41 years; 1 male and 1 female) and OA patients (n = 11; ages 64-79 years;
      2 male and 9 female). The association between its production in chondrocytes and
      the grade of cartilage destruction was established on full-depth cartilage
      biopsies. The functional activity of adiponectin in OA cartilage was determined
      from the relation between the expression of adiponectin, its receptor, cartilage
      specific components and factors involved in matrix degradation, and from the
      chondrocyte response to the full-length or the globular form of adiponectin.
      RESULTS: Adiponectin was not detected in healthy cartilage. Conversely, the
      adipokine was up-regulated in damaged tissue, but no strong association with the
      grade of cartilage destruction was found. We showed a positive correlation
      between adiponectin and mPGES or MMP-13 while AdipoR1 was related to the
      expression of type 2 collagen, aggrecan and Sox9. The full-length form of
      adiponectin but not the globular isoform, stimulated the production of PGE2 and
      MMP-13 activity in cultured human chondrocytes. CONCLUSIONS: The elevated level
      of adiponectin found in chondrocytes from OA patients might contribute to matrix
      remodelling during OA, the full-length isoform being the single active form.

PMID- 24462672
TI  - OARSI guidelines for the non-surgical management of knee osteoarthritis.
AB  - OBJECTIVE: To develop concise, up-to-date, patient-focused, evidence-based,
      expert consensus guidelines for the management of knee osteoarthritis (OA),
      intended to inform patients, physicians, and allied healthcare professionals
      worldwide. METHOD: Thirteen experts from relevant medical disciplines (primary
      care, rheumatology, orthopedics, physical therapy, physical medicine and
      rehabilitation, and evidence-based medicine), three continents and ten countries
      (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and
      Canada) and a patient representative comprised the Osteoarthritis Guidelines
      Development Group (OAGDG). Based on previous OA guidelines and a systematic
      review of the OA literature, 29 treatment modalities were considered for
      recommendation. Evidence published subsequent to the 2010 OARSI guidelines was
      based on a systematic review conducted by the OA Research Society International
      (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE,
      Google Scholar, Web of Science, and the Cochrane Central Register of Controlled
      Trials were initially searched in first quarter 2012 and last searched in March
      2013. Included evidence was assessed for quality using Assessment of Multiple
      Systematic Reviews (AMSTAR) criteria, and published criticism of included
      evidence was also considered. To provide recommendations for individuals with a
      range of health profiles and OA burden, treatment recommendations were stratified
      into four clinical sub-phenotypes. Consensus recommendations were produced using
      the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were
      recommended as Appropriate, Uncertain, or Not Appropriate, for each of four
      clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. RESULTS:
      Appropriate treatment modalities for all individuals with knee OA included
      biomechanical interventions, intra-articular corticosteroids, exercise (land
      based and water-based), self-management and education, strength training, and
      weight management. Treatments appropriate for specific clinical sub-phenotypes
      included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking
      stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2
      selective and non-selective), and topical NSAIDs. Treatments of uncertain
      appropriateness for specific clinical sub-phenotypes included acupuncture,
      avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine,
      intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip,
      transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not
      appropriate included risedronate and electrotherapy (neuromuscular electrical
      stimulation). CONCLUSION: These evidence-based consensus recommendations provide
      guidance to patients and practitioners on treatments applicable to all
      individuals with knee OA, as well as therapies that can be considered according
      to individualized patient needs and preferences.

PMID- 24462673
TI  - Cytotoxic cucurbitane triterpenoids isolated from the rhizomes of Hemsleya
      amabilis.
AB  - Two new cucurbitane triterpenoids, 7beta-hydroxycucurbitacin F-25-O-acetate (1)
      and 2beta,3beta,20(S),26,27-pentahydroxy-16alpha,23(S)-epoxycucurbita-5,24-dien
      11-one (2) along with eleven known cucurbitane triterpenoids (3-13, resp.) were
      isolated from the rhizomes of Hemsleya amabilis Diels. The chemical structures of
      the new isolated compounds were elucidated unambiguously by spectroscopic data
      analysis. The cytotoxic activities of the isolated cucurbitane triterpenoids were
      evaluated against the HeLa human cancer cell lines. Hemslecin A (5), the main
      ingredient of H. amabilis, exhibited the significant cytotoxicity with IC50 value
      of 0.389 MUM.

PMID- 24462674
TI  - Celecoxib offsets the negative renal influences of cyclosporine via modulation of
      the TGF-beta1/IL-2/COX-2/endothelin ET(B) receptor cascade.
AB  - Endothelin (ET) signaling provokes nephrotoxicity induced by the
      immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i):
      celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal
      derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor
      signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20
      mg/kg/day) significantly increased biochemical indices of renal function (serum
      urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming
      growth factor-beta1, TGF-beta1). Histologically, CSA caused renal tubular atrophy
      along with interstitial fibrosis. These detrimental renal effects of CSA were
      largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We
      also report that cortical glomerular and medullary tubular protein expressions of
      COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values
      in rats treated simultaneously with celecoxib. The importance of ET(B) receptors
      in renal control and in the CSA-celecoxib interaction was further verified by the
      findings (i) most of the adverse biochemical, inflammatory, and histopathological
      profiles of CSA were replicated in rats treated with the endothelin ETB receptor
      antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those
      of CSA, were alleviated in rats treated concurrently with celecoxib. Together,
      the data suggest that the facilitation of the interplay between the TGF-beta1/IL
      2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular
      mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in
      rats.

PMID- 24462675
TI  - Letter to the editor.

PMID- 24462676
TI  - Metabolic changes in serum steroids induced by total-body irradiation of female
      C57B/6 mice.
AB  - The short- and long-term effects of a single exposure to gamma radiation on
      steroid metabolism were investigated in mice. Gas chromatography-mass
      spectrometry was used to generate quantitative profiles of serum steroid levels
      in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and
      4Gy. Following TBI, serum samples were collected at the pre-dose time point and
      1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5beta
      DHP, 5alpha-DHP, and 20alpha-DHP showed a significant down-regulation following
      short-term exposure to 4Gy, with the exception of 20alpha-DHP, which was
      significantly decreased at each of the time points measured. The corticosteroids
      5alpha-THDOC and 5alpha-DHB were significantly elevated at each of the time
      points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH
      cholestoerol showed a dose-related elevation after irradiation that reached
      significance in the high dose group at the 6- and 9-month time points. 

PMID- 24462678
TI  - Improving the ablation efficiency of excimer laser systems with higher repetition
      rates through enhanced debris removal and optimized spot pattern.
AB  - PURPOSE: To evaluate the reasons for the required increased radiant exposure for
      higher-repetition-rate excimer lasers and determine experimentally possible
      compensations to achieve equivalent ablation profiles maintaining the same single
      pulse energies and radiant exposures for laser repetition rates ranging from 430
      to 1000 Hz. SETTING: Schwind eye-tech-solutions GmbH and Co. KG, Kleinostheim,
      Germany. DESIGN: Experimental study. METHODS: Poly(methyl methacrylate) (PMMA)
      plates were photoablated. The pulse laser energy was maintained during all
      experiments; the effects of the flow of the debris removal, the shot pattern for
      the correction, and precooling the PMMA plates were evaluated in terms of
      achieved ablation versus repetition rate. RESULTS: The mean ablation performance
      ranged from 88% to 100%; the variability between the profile measurements ranged
      from 1.4% to 6.2%. Increasing the laser repetition rate from 430 Hz to 1000 Hz
      reduced the mean ablation performance from 98% to 91% and worsened the
      variability from 1.9% to 4.3%. Increasing the flow of the debris removal,
      precooling the PMMA plates to -18 degrees C, and adapting the shot pattern for
      the thermal response of PMMA to excimer ablation helped stabilize the
      variability. Only adapting the shot pattern for the thermal response of PMMA to
      excimer ablation helped stabilize the mean ablation performance. CONCLUSIONS: The
      ablation performance of higher-repetition-rate excimer lasers on PMMA improved
      with improvements in the debris removal systems and shot pattern. More powerful
      debris removal systems and smart shot patterns in terms of thermal response
      improved the performance of these excimer lasers.

PMID- 24462677
TI  - TAB1: a target of triptolide in macrophages.
AB  - Triptolide (TP) is a biologically active diterpene triepoxide from the Chinese
      herb Tripterygium wilfordii Hook f. Here, we identify and explore TAB1 as the
      binding target of TP in macrophages by using a comprehensive approach combining
      pull-down assays, in vitro assessments, and pharmaceutical and biological
      evaluation. We discover that TP inhibits TAK1 kinase activity by interfering with
      the formation of the TAK1-TAB1 complex, and the binding affinity of TP to TAB1
      correlates highly with the inhibitory activity of TP against MAPK pathway
      activation in macrophages. We also find that the amino acid sequence between
      positions 373 and 502 of TAB1 is required for TP interaction. Our results suggest
      that TP could be a selective small-molecule inhibitor of the TAK1-TAB1 complex
      and that TAB1 could be a potential therapeutic target in inflammatory disease.

PMID- 24462679
TI  - MiR-874 promotes intestinal barrier dysfunction through targeting AQP3 following
      intestinal ischemic injury.
AB  - Intestinal ischemic injury is a significant clinical problem arising from
      diseases or as a complication of abdominal surgery. Our previous study showed
      aquaporin 3 is involved in intestinal barrier impairment. Here, we revealed that
      intestinal ischemia induced a time-dependent increase of miR-874 expression and a
      time-dependent decrease of AQP3 expression, and the level of miR-874 expression
      was inversely related to AQP3 protein expression. In addition, miR-874 promoted
      the paracellular permeability in vitro through targeting 3'UTR of AQP3. Two of
      the tight junction proteins, Occludin and Claudin-1, were found to be involved in
      miR-874-induced intestinal barrier dysfunction. 

PMID- 24462680
TI  - Hepatitis B virus X increases immune cell recruitment by induction of chemokine
      SDF-1.
AB  - Hepatitis B virus X protein is a major factor in the HBV-induced disease
      developments. Stromal cell-derived factor-1 is a small cytokine that is strongly
      chemotactic for lymphocytes. We explored the role of HBx on recruitment of HBV
      induced virus-nonspecific immune cells into liver. Immune cell recruitment and
      SDF-1 expression level significantly increased in livers of HBx-transgenic mice
      and X-box binding protein-1 significantly increased SDF-1 gene expression.
      Finally, we confirmed that immune cell recruitment into liver tissues of HBx-TG
      mice was diminished by a chemokine receptor antagonist. Therefore, HBx increases
      ER stress-dependent SDF-1 expression and induces HBV-induced immune cell
      recruitment into liver. 

PMID- 24462681
TI  - Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74
      dephosphorylation.
AB  - Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer
      nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here,
      we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the
      PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74
      phosphorylation at concentrations reported to specifically target PP2A. In line
      with this, purified PP2A, but not PP1, dephosphorylated recombinant pSer-74-dCK.
      In cell lysates, the Ser-74-dCK phosphatase activity was found to be latent,
      Mn(2+)-activated, responsive to PP2A inhibitors, and diminished after PP2A
      immunodepletion. Use of siRNAs allowed concluding definitively that PP2A
      constitutively dephosphorylates dCK in cells and negatively regulates its
      activity. 

PMID- 24462682
TI  - Genes and evolution of two-domain toxins from lynx spider venom.
AB  - Spiderines are comparatively long polypeptide toxins (~110 residues) from lynx
      spiders (genus Oxyopes). They are built of an N-terminal linear cationic domain
      (~40 residues) and a C-terminal knottin domain (~60 residues). The linear domain
      empowers spiderines with strong cytolytic activity. In the present work we report
      16 novel spiderine sequences from Oxyopes takobius and Oxyopes lineatus
      classified into two subfamilies. Strikingly, negative selection acts on both
      linear and knottin domains. Genes encoding Oxyopes two-domain toxins were
      sequenced and found to be intronless. We further discuss a possible scenario of
      lynx spider modular toxin evolution. 

PMID- 24462683
TI  - Interaction between nucleophosmin and HBV core protein increases HBV capsid
      assembly.
AB  - Host factors are involved in Hepatitis B virus (HBV) genome replication and
      capsid formation during the viral life cycle. A host factor, nucleophosmin (B23),
      was found to bind to HBV core protein dimers, but its functional role has not
      been studied. This interaction promoted HBV capsid assembly and decreased the
      degree of capsid dissociation when subjected to denaturant treatments in vitro.
      In addition, inhibition of B23 reduced intracellular capsid formation resulting
      in a decrease of HBV production in HepG2.2.15 cells. These results provide
      important evidence that B23 acts on core capsid assembly via its interaction with
      HBV core dimers. 

PMID- 24462684
TI  - NMR analyses on the interactions of the yeast Tim50 C-terminal region with the
      presequence and Tim50 core domain.
AB  - The mitochondrial targeting signal in the presequence of mitochondrial precursor
      proteins is recognized by Tom20 and subsequently by Tim50 in mitochondria. Yeast
      Tim50 contains two presequence binding sites in the conserved core domain and in
      the fungi-specific C-terminal presequence binding domain (PBD). We report the NMR
      analyses on interactions of a shorter variant of PBD (sPBD), a shorter variant of
      PBD, with presequences. The presequence is recognized by sPBD in a similar manner
      to Tom20. sPBD can also bind to the core domain of Tim50 through the presequence
      binding region, which could promote transfer of the presequence from sPBD to the
      core domain in Tim50. 

PMID- 24462685
TI  - Human chitotriosidase CHIT1 cross reacts with mammalian-like substrates.
AB  - Humans do not synthesize chitin, yet they produce a number of active and inactive
      chitinases. One of the active enzymes is chitotriosidase whose serum levels are
      elevated in a number of diseases such as Gaucher's disease and upon fungal
      infection. Since the biological role of chitotriosidase in disease pathogenesis
      is not understood we screened a panel of mammalian GlcNAc-containing
      glycoconjugates as alternate substrates. LacNAc and LacdiNAc-terminating
      substrates are hydrolyzed, the latter with a turnover comparable to that of pNP
      chitotriose. Glycolipids or glycoproteins with LacNAc and LacdiNAc represent
      potential chitinase substrates and the subsequent alteration of glycosylation
      pattern could be a factor in disease pathogenesis. 

PMID- 24462686
TI  - Transcription factor AP-2delta regulates the expression of polysialyltransferase
      ST8SIA2 in chick retina.
AB  - The AP-2delta transcription factor is restricted to a subset of retinal ganglion
      cells. Overexpression of AP-2delta in chick retina results in induction of
      polysialylated neural cell adhesion molecule (PSA-NCAM) accompanied by misrouting
      and bundling of ganglion cell axons. Two polysialyltransferases, ST8SIA2 and
      ST8SIA4, are responsible for polysialylation of NCAM. Here, we investigate the
      mechanism driving the increase in PSA-NCAM observed upon AP-2delta
      overexpression. We show that ST8SIA2 is induced by AP-2delta overexpression in
      chick retina. We use chromatin immunoprecipitation and gel shift assays to
      demonstrate direct interaction between AP-2delta and the ST8SIA2 promoter. We
      propose that up-regulation of ST8SIA2 upon AP-2delta overexpression in retina
      increases ectopic polysialylation of NCAM which in turn causes premature bundling
      of axons and alters axonal response to guidance cues. 

PMID- 24462687
TI  - Decreased IL-10 expression in stefin B-deficient macrophages is regulated by the
      MAP kinase and STAT-3 signaling pathways.
AB  - Innate immune responses are tightly regulated to avoid excessive activation and
      subsequent inflammatory damage to the host, and interleukin-10 (IL-10) plays a
      crucial role in preventing inflammation. Stefin B (cystatin B) is an endogenous
      inhibitor of cysteine proteinases. In stefin B-deficient bone marrow-derived
      macrophages (BMDMs), we detected an increase in the induction of the LPS-induced
      pro-inflammatory signal nitric oxide (NO) but decreased IL-10 expression. The
      phosphorylation of ERK and p38 MAP-kinases was significantly decreased in stefin
      B-deficient macrophages, as was STAT-3 phosphorylation. These findings show that
      stefin B influences the expression of anti-inflammatory IL-10 in response to the
      TLR4 agonist LPS. 

PMID- 24462688
TI  - Effects of palmitoylation on the diffusional movement of BKCa channels in live
      cells.
AB  - BKCa channels are palmitoylated at a cluster of cysteine residues within the
      cytosolic linker connecting the 1st and 2nd transmembrane domains, and this lipid
      modification affects their surface expression. To verify the effects of
      palmitoylation on the diffusional dynamics of BKCa channels, we investigated
      their lateral movement. Compared to wild-type channels, the movement of mutant
      palmitoylation-deficient channels was much less confined and close to random. The
      diffusion of the mutant channel was also much faster than that of the wild type.
      Thus, the lateral movement of BKCa channels is greatly influenced by
      palmitoylation. 

PMID- 24462689
TI  - GC content fluctuation around plant small RNA-generating sites.
AB  - GC content of small RNA-generating sites and their flanking sequences in
      Arabidopsis thaliana and rice was systematically analyzed in silico. High GC
      content fluctuation (GCF) is observed at the borders of sRNA sites, while the GCF
      within sRNA sites is low. Furthermore, the GC content along sequences of some
      miniature inverted-repeat transposable element (MITE) families coincides with the
      abundance of MITE-derived small RNAs. The GCF within tasiRNA clusters is
      negatively correlated with its phasing score. We conclude that high GC content
      and low GCF could increase the expression of small RNA. Our results provide
      further insights on small RNA expression, which may be applied to improve the
      silencing efficiency of RNAi and virus-induced gene silencing. 

PMID- 24462690
TI  - The Ca(2+)-dependent interaction of calpastatin domain L with the C-terminal tail
      of the Cav1.2 channel.
AB  - To demonstrate the interaction of calpastatin (CS) domain L (CSL) with Cav1.2
      channel, we investigated the binding of CSL with various C-terminus-derived
      peptides at~free, 100 nM, 10 MUM, and 1mM Ca(2+) by using the GST pull-down assay
      method. Besides binding with the IQ motif, CSL was also found to bind with the
      PreIQ motif. With increasing [Ca(2+)], the affinity of the CSL-IQ interaction
      gradually decreased, and the affinity of the CSL-PreIQ binding gradually
      increased. The results suggest that CSL may bind with both the IQ and PreIQ
      motifs of the Cav1.2 channel in different Ca(2+)-dependent manners.

PMID- 24462691
TI  - Steady-state kinetic mechanism of LodA, a novel cysteine tryptophylquinone
      dependent oxidase.
AB  - LodA is a novel lysine-epsilon-oxidase which possesses a cysteine
      tryptophylquinone cofactor. It is the first tryptophylquinone enzyme known to
      function as an oxidase. A steady-state kinetic analysis shows that LodA obeys a
      ping-pong kinetic mechanism with values of kcat of 0.22+/-0.04 s(-1), Klysine of
      3.2+/-0.5 MUM and KO2 of 37.2+/-6.1 MUM. The kcat exhibited a pH optimum at 7.5
      while kcat/Klysine peaked at 7.0 and remained constant to pH 8.5. Alternative
      electron acceptors could not effectively substitute for O2 in the reaction. A
      mechanism for the reductive half reaction of LodA is proposed that is consistent
      with the ping-pong kinetics.

PMID- 24462692
TI  - Molecular modeling and residue interaction network studies on the mechanism of
      binding and resistance of the HCV NS5B polymerase mutants to VX-222 and ANA598.
AB  - Hepatitis C virus (HCV) NS5B protein is an RNA-dependent RNA polymerase (RdRp)
      with essential functions in viral genome replication and represents a promising
      therapeutic target to develop direct-acting antivirals (DAAs). Multiple
      nonnucleoside inhibitors (NNIs) binding sites have been identified within the
      polymerase. VX-222 and ANA598 are two NNIs targeting thumb II site and palm I
      site of HCV NS5B polymerase, respectively. These two molecules have been shown to
      be very effective in phase II clinical trials. However, the emergence of
      resistant HCV replicon variants (L419M, M423T, I482L mutants to VX-222 and M414T,
      M414L, G554D mutants to ANA598) has significantly decreased their efficacy. To
      elucidate the molecular mechanism about how these mutations influenced the drug
      binding mode and decreased drug efficacy, we studied the binding modes of VX-222
      and ANA598 to wild-type and mutant polymerase by molecular modeling approach.
      Molecular dynamics (MD) simulations results combined with binding free energy
      calculations indicated that the mutations significantly altered the binding free
      energy and the interaction for the drugs to polymerase. The further per-residue
      binding free energy decomposition analysis revealed that the mutations decreased
      the interactions with several key residues, such as L419, M423, L474, S476, I482,
      L497, for VX-222 and L384, N411, M414, Y415, Q446, S556, G557 for ANA598. These
      were the major origins for the resistance to these two drugs. In addition, by
      analyzing the residue interaction network (RIN) of the complexes between the
      drugs with wild-type and the mutant polymerase, we found that the mutation
      residues in the networks involved in the drug resistance possessed a relatively
      lower size of topology centralities. The shift of betweenness and closeness
      values of binding site residues in the mutant polymerase is relevant to the
      mechanism of drug resistance of VX-222 and ANA598. These results can provide an
      atomic-level understanding about the mechanisms of drug resistance conferred by
      the studied mutations and will be helpful to design more potent inhibitors which
      could effectively overcome drug resistance of antivirus agents. 

PMID- 24462693
TI  - Murine models of hepatitis C: what can we look forward to?
AB  - The study of interactions between hepatitis C virus (HCV) with its mammalian
      host, along with the development of more effective therapeutics and vaccines has
      been delayed by the lack of a suitable small animal model. HCV readily infects
      only humans and chimpanzees, which poses logistic, economic and ethical
      challenges with analyzing HCV infection in vivo. Progress has been made in
      understanding the determinants that dictate HCV's narrow host range providing a
      blueprint for constructing a mouse model with inheritable susceptibility to HCV
      infection. Indeed, genetically humanized mice were generated that support viral
      uptake, replication and production of infectious virions--albeit at low levels.
      These efforts are complemented with attempts to select for viral variants that
      are inherently more capable of replicating in non-human species. In parallel,
      engraftment of relevant human tissues into improved xenorecipients is being
      continuously refined. Incorporating advances in stem-cell-biology and tissue
      engineering may allow the generation of patient-specific humanized mice.
      Construction of such mouse "avatars" may allow analyzing functionally patient
      specific differences with respect to susceptibility to infection, disease
      progression and responses to treatment. In this review, we discuss the three,
      before mentioned approaches to overcome current species barriers and generate a
      small animal model for HCV infection, i.e. genetic modification of mice to
      increase their susceptibility to the virus; genetic modification of HCV, to
      increase its pathogenicity for mice; and the introduction of human liver and
      immune cells into immunodeficient mice, to create "humanized" mice. Although in
      the foreseeable future there will not be a single model that perfectly mimics the
      natural course of HCV in humans there is reason for optimism. The spectrum of
      murine animal models for hepatitis C provides a broad arsenal for analyzing the
      disease. These models may play an important role by prioritizing vaccine
      candidates and possibly refining combination anti-viral drug therapies. This
      article forms part of a symposium in Anti-viral Research on "Hepatitis C: next
      steps toward global eradication."

PMID- 24462695
TI  - Maternal antibodies by passive immunization with formalin inactivated respiratory
      syncytial virus confer protection without vaccine-enhanced disease.
AB  - Maternal immunization of mice with formalin inactivated respiratory syncytial
      virus (FI-RSV) resulted in the passive transfer of RSV antibodies but not
      cellular components to the offspring. The offspring born to FI-RSV immunized
      mothers showed serum RSV neutralizing activity, effectively controlled lung viral
      loads without vaccine-enhanced disease, did not induce pulmonary eosinophilia,
      and cytokine producing cells after live RSV infection. Therefore, this study
      provides evidence that maternal immunization provides an in vivo model in
      investigating the roles of antibodies independent of cellular components. 

PMID- 24462694
TI  - Development and application of reporter-expressing mononegaviruses: current
      challenges and perspectives.
AB  - Reverse genetics allows the generation of recombinant viruses entirely from cDNA.
      One application of this technology is the creation of reporter-expressing
      viruses, which greatly increase the detail and ease with which these viruses can
      be studied. However, there are a number of challenges when working with reporter
      expressing viruses. Both the reporter protein itself as well as the genetic
      manipulations within the viral genome required for expression of this reporter
      can result in altered biological properties of the recombinant virus, and lead to
      attenuation in vitro and/or in vivo. Further, instability of reporter expression
      and purging of the genetic information encoding for the reporter from the viral
      genome can be an issue. Finally, a practical challenge for in vivo studies lies
      in the attenuation of light signals when traversing tissues. Novel expression
      strategies and the continued development of brighter, red and far-red shifted
      reporters and the increased use of bioluminescent reporters for in vivo
      applications promise to overcome some of these limitations in future. However, a
      "one size fits all" approach to the design of reporter-expressing viruses has
      thus far not been possible. Rather, a reporter suited to the intended application
      must be selected and an appropriate expression strategy and location for the
      reporter in the viral genome chosen. Still, attenuating effects of the reporter
      on viral fitness are difficult to predict and have to be carefully assessed with
      respect to the intended application. Despite these limitations the generation of
      suitable reporter-expressing viruses will become more common as technology and
      our understanding of the intricacies of viral gene expression and regulation
      improves, allowing deeper insight into virus biology both in living cells and in
      animals. 

PMID- 24462697
TI  - Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola
      virus infection in a mouse model.
AB  - Filoviruses cause disease with high case fatality rates and are considered
      biological threat agents. Licensed post-exposure therapies that can be
      administered by the oral route are desired for safe and rapid distribution and
      uptake in the event of exposure or outbreaks. Favipiravir or T-705 has broad
      antiviral activity and has already undergone phase II and is undergoing phase III
      clinical trials for influenza. Here we report the first use of T-705 against
      Ebola virus. T-705 gave 100% protection against aerosol Ebola virus E718
      infection; protection was shown in immune-deficient mice after 14 days of twice
      daily dosing. T-705 was also shown to inhibit Ebola virus infection in cell
      culture. T-705 is likely to be licensed for use against influenza in the near
      future and could also be used with a new indication for filovirus infection.

PMID- 24462696
TI  - The competitive binding between inhibitors and substrates of HCV NS3/4A protease:
      a general mechanism of drug resistance.
AB  - Hepatitis C virus (HCV) infection is a serious public health problem throughout
      the world. Great success has been achieved in developing inhibitors targeting the
      HCV NS3/4A protease over the past decade, but the rapid emergence of drug
      resistant mutations greatly compromises the efficacy of antiviral drugs or drug
      candidates. According to the substrate envelope hypothesis (Romano et al., 2010),
      severe drug resistant mutations would always occur where the inhibitors protrude
      from the substrate envelope, defined as a consensus volume occupied by the viral
      substrates in the active site of the NS3/4A protease. However, the substrate
      envelope hypothesis just qualitatively assesses the impact of mutations to a
      specific inhibitor, but no quantitative data is obtained. To remedy the weakness,
      the dynamic binding patterns of HCV NS3/4A protease inhibitors or substrates were
      investigated by molecular dynamics (MD) simulations and continuum solvation
      binding affinity predictions in this study. By comparing the quantitative binding
      profiles between the substrates and inhibitors, derived from the free energy
      decomposition analysis, we observed most residues involved in drug resistance
      form stronger interactions with the inhibitors than with the substrates, which is
      roughly coincident with the substrate envelope hypothesis and supports the
      general mechanism of drug resistance: the critical resistant mutations impair
      more to the binding of inhibitors than that of substrates. Furthermore, our
      predictions illustrate that the natural substrates of NS3/4A form balanced
      interactions with the strands 135-139 and 154-160 whereas the inhibitors cannot.
      Therefore, to overcome drug resistance, it may be necessary to restore the
      interaction balance between the two strands and the drug candidates. To our
      disappointment, the underlying resistant mechanisms of some mutations could not
      be well captured by just comparing the binding profiles of inhibitors and
      substrates, and more studies should be proceeded to propose a general drug
      resistance mechanism. 

PMID- 24462699
TI  - Guidance on posterior resin composites: Academy of Operative Dentistry - European
      Section.
AB  - There have been many developments in operative dentistry in recent years,
      including a progressive shift to the use of resin composites, rather than dental
      amalgam, in the restoration of posterior teeth. This shift allows the adoption of
      minimal intervention approaches, thereby helping to conserve and preserve
      remaining tooth tissues and structures. This paper presents the position of the
      Academy of Operative Dentistry European Section (AODES) in relation to posterior
      resin composites. The AODES considers adhesively bonded resin composites of
      suitable composition and properties to be the "material of choice" for use in
      direct minimal intervention approaches to the restoration of posterior teeth. In
      so doing, the AODES emphasises the importance of the practice of evidence-based
      minimal intervention dentistry, including the use of refurbishment and repair
      techniques to extend the longevity of restorations. Guidance, based on best
      available evidence, has been made in relation to certain aspects of resin
      composite placement techniques in posterior teeth. 

PMID- 24462698
TI  - The role of low-grade inflammation and metabolic flexibility in aging and
      nutritional modulation thereof: a systems biology approach.
AB  - Aging is a biological process characterized by the progressive functional decline
      of many interrelated physiological systems. In particular, aging is associated
      with the development of a systemic state of low-grade chronic inflammation
      (inflammaging), and with progressive deterioration of metabolic function. Systems
      biology has helped in identifying the mediators and pathways involved in these
      phenomena, mainly through the application of high-throughput screening methods,
      valued for their molecular comprehensiveness. Nevertheless, inflammation and
      metabolic regulation are dynamical processes whose behavior must be understood at
      multiple levels of biological organization (molecular, cellular, organ, and
      system levels) and on multiple time scales. Mathematical modeling of such
      behavior, with incorporation of mechanistic knowledge on interactions between
      inflammatory and metabolic mediators, may help in devising nutritional
      interventions capable of preventing, or ameliorating, the age-associated
      functional decline of the corresponding systems. 

PMID- 24462700
TI  - Bonding ability of 4-META self-etching primer used with 4-META/MMA-TBB resin to
      enamel and dentine: primary vs permanent teeth.
AB  - OBJECTIVES: The present study compared the efficacies of the self-etching Teeth
      Primer (TP: 4-META), and the etchants Red Activator (RA; 65% phosphoric acid) and
      Green Activator (GA; 10% citric acid with 3% ferric chloride), for bonding to
      enamel and dentine of human primary and permanent teeth, when used with 4
      META/MMA-TBB resin (Bondfill SB). METHODS: Forty-eight non-carious primary
      canines and third molars were used. Eight groups were prepared: Group 1 (primary
      enamel with RA), Group 2 (permanent enamel with RA), Group 3 (primary enamel with
      TP), Group 4 (permanent enamel with TP), Group 5 (primary dentine with GA), Group
      6 (permanent dentine with GA), Group 7 (primary dentine with TP) and Group 8
      (permanent dentine with TP). Micro-tensile bond strengths (MTBS) were measured
      and analyzed statistically using ANOVAs and Tukey HSD tests at alpha=0.05.
      Efficacy of etching/priming and the morphology of bonded interfaces were observed
      with SEM. RESULTS: Etching/priming efficacy of TP on enamel was low. The MTBS of
      Group 2 was significantly higher than the other groups (Groups 1, 3 and 4). For
      dentine, significant differences in MTBS were observed, in the order of Groups
      6>8>7=5 (p<0.05). The MTBSs of permanent dentine were significantly higher than
      primary dentine. For primary teeth, there was no significant difference in the
      MTBSs between enamel and dentine, irrespective of primer or etchant (p>0.05).
      CONCLUSION: TP primer/Bondfill SB may be used as an alternative to other
      adhesive/resin composite systems for bonding to enamel and dentine of primary
      teeth.

PMID- 24462701
TI  - Confirmation of theoretical colour predictions for layering dental composite
      materials.
AB  - OBJECTIVE: The aim of this study is to confirm the theoretical colour predictions
      for single and double layers of dental composite materials on an opaque backing.
      METHODS: Single and double layers of composite resins were fabricated, placed in
      optical contact with a grey backing and measured for spectral radiance. The
      spectral reflectance and colour were directly determined. Absorption and
      scattering coefficients as previously reported, the measured thickness of the
      single layers and the effective reflectance of the grey backing were utilized to
      theoretically predict the reflectance of the single layer using corrected Kubelka
      Munk reflectance theory. For double layers the predicted effective reflectance of
      the single layer was used as the reflectance of the backing of the second layer
      and the thickness of the second layer was used to predict the reflectance of the
      double layer. Colour differences, using both the CIELAB and CIEDE2000 formulae,
      measured the discrepancy between each directly determined colour and its
      corresponding theoretical colour. RESULTS: The colour difference discrepancies
      generally ranged around the perceptibility threshold but were consistently below
      the respective acceptability threshold. CONCLUSION: This theory can predict the
      colour of layers of composite resin within acceptability limits and generally
      also within perceptibility limits. CLINICAL SIGNIFICANCE: This theory could
      therefore be incorporated into computer-based optical measuring instruments that
      can automate the shade selections for layers of a more opaque first layer under a
      more translucent second layer for those clinical situations where an underlying
      background colour and a desirable final colour can be measured.

PMID- 24462702
TI  - Yeasts are essential for cocoa bean fermentation.
AB  - Cocoa beans (Theobroma cacao) are the major raw material for chocolate production
      and fermentation of the beans is essential for the development of chocolate
      flavor precursors. In this study, a novel approach was used to determine the role
      of yeasts in cocoa fermentation and their contribution to chocolate quality.
      Cocoa bean fermentations were conducted with the addition of 200ppm Natamycin to
      inhibit the growth of yeasts, and the resultant microbial ecology and metabolism,
      bean chemistry and chocolate quality were compared with those of normal (control)
      fermentations. The yeasts Hanseniaspora guilliermondii, Pichia kudriavzevii and
      Kluyveromyces marxianus, the lactic acid bacteria Lactobacillus plantarum and
      Lactobacillus fermentum and the acetic acid bacteria Acetobacter pasteurianus and
      Gluconobacter frateurii were the major species found in the control fermentation.
      In fermentations with the presence of Natamycin, the same bacterial species grew
      but yeast growth was inhibited. Physical and chemical analyses showed that beans
      fermented without yeasts had increased shell content, lower production of
      ethanol, higher alcohols and esters throughout fermentation and lesser presence
      of pyrazines in the roasted product. Quality tests revealed that beans fermented
      without yeasts were purplish-violet in color and not fully brown, and chocolate
      prepared from these beans tasted more acid and lacked characteristic chocolate
      flavor. Beans fermented with yeast growth were fully brown in color and gave
      chocolate with typical characters which were clearly preferred by sensory panels.
      Our findings demonstrate that yeast growth and activity were essential for cocoa
      bean fermentation and the development of chocolate characteristics. 

PMID- 24462703
TI  - Impact of cold plasma on Citrobacter freundii in apple juice: inactivation
      kinetics and mechanisms.
AB  - Various studies have shown that cold plasma is capable of inactivating
      microorganisms located on a variety of food surfaces, food packaging materials
      and process equipment under atmospheric pressure conditions; however, less
      attention has been paid to the impact of cold plasma on microorganisms in liquid
      foodstuffs. The present study investigates cold plasma's ability to inactivate
      Citrobacter freundii in apple juice. Optical emission spectroscopy (OES) and
      temperature measurements were performed to characterise the plasma source. The
      plasma-related impact on microbial loads was evaluated by traditional plate count
      methods, while morphological changes were determined using scanning electron
      microscopy (SEM). Physiological property changes were obtained through flow
      cytometric measurements (membrane integrity, esterase activity and membrane
      potential). In addition, mathematical modelling was performed in order to achieve
      a reliable prediction of microbial inactivation and to establish the basis for
      possible industrial implementation. C. freundii loads in apple juice were reduced
      by about 5 log cycles after a plasma exposure of 480s using argon and 0.1% oxygen
      plus a subsequent storage time of 24h. The results indicate that a direct contact
      between bacterial cells and plasma is not necessary for achieving successful
      inactivation. The plasma-generated compounds in the liquid, such as H2O2 and most
      likely hydroperoxy radicals, are particularly responsible for microbial
      inactivation. 

PMID- 24462704
TI  - Decreased expression and DNA methylation levels of GATAD1 in preeclamptic
      placentas.
AB  - Expression of syncytin-1, or the human endogenous retroviral family W member 1
      (HERVWE1) in human placental trophoblasts is regulated by DNA methylation.
      Increased DNA methylation and decreased expression of syncytin-1 have been
      observed in preeclamptic placentas. The syncytin-1-mediated fusogenic as well as
      non-fusogenic activities, e.g., cell cycle promotion, anti-apoptosis, and immune
      suppression, are implicated in the pathogenic changes in preeclamptic placentas.
      It is noteworthy that in a close vicinity to syncytin-1 there are two genes,
      peroxisome biogenesis factor 1 (PEX1) and GATA zinc finger domain containing 1
      (GATAD1), as well as multiple CpG islands around these genes. In this study we
      determined if these adjacent genes might, like syncytin-1, subject to epigenetic
      regulation in preeclamptic placentas. Data from quantitative real-time PCR and
      Western blotting indicated that while PEX1 expression remained stable, GATAD1
      expression was significantly decreased in the third-trimester placentas
      associated with preeclampsia than those associated with normal pregnancy.
      Immunohistochemistry detected high GATAD1 expression in trophoblast linage, and
      confirmed its reduced levels in preeclamptic placentas. However, COBRA and
      bisulfate sequencing detected decreased DNA methylation in levels in the 3
      [prime] region of GATAD1 gene in preeclamptic placentas. The positive correlation
      between 3 [prime] methylation and GATAD1 expression was confirmed by treatment of
      choriocarcinoma JAR cells with DNMT inhibitor. These data pointed to a potential
      role of GATAD1 for the syncytium deficiency often associated with preeclamptic
      placentas. The sharp contrast of the methylation alterations for the closely
      positioned GATAD1 and HERVWE1 may provide a useful model for studying the
      accurate control of DNA methylation as well as their positive and negative impact
      on gene expression in placental trophoblasts. 

PMID- 24462705
TI  - TLR3 regulates mycobacterial RNA-induced IL-10 production through the PI3K/AKT
      signaling pathway.
AB  - Cytokine induction in response to Mycobacterium tuberculosis (Mtb) infection is
      critical for pathogen control, by (i) mediating innate immune effector functions
      and (ii) instructing specific adaptive immunity. IL-10 is an important anti
      inflammatory cytokine involved in pathogenesis of tuberculosis (TB). Here, we
      show that TLR3, a sensor of extracellular viral or host RNA with stable stem
      structures derived from infected or damaged cells, is essential for Mtb-induced
      IL-10 production. Upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG)
      infection, TLR3(-/-) macrophages expressed lower IL-10 but higher IL-12p40
      production, accompanied by reduced phosphorylation of AKT at Ser473. BCG-infected
      TLR3(-/-) mice exhibited reduced IL-10 but elevated IL-12 expression compared to
      controls. Moreover, higher numbers of splenic Th1 cells and reduced pulmonary
      bacterial burden and tissue damage were observed in BCG-infected TLR3(-/-) mice.
      Finally, BCG RNA induced IL-10 in macrophages via TLR3-mediated activation of
      PI3K/AKT. Our findings demonstrate a critical role of TLR3-mediated regulation in
      the pathogenesis of mycobacterial infection involving mycobacterial RNA, which
      induces IL-10 through the PI3K/AKT signaling pathway. 

PMID- 24462706
TI  - Stratification and delineation of gastric cancer signaling by in vitro
      transcription factor activity profiling and integrative genomics.
AB  - Integrative functional genomic approaches are helpful in delineating the complex
      dysregulations in cancers. In the present study, in vitro activity profiling of
      45 signaling pathway driven transcription factors in eight gastric cancer cell
      lines and direct comparison with genome-wide profiles of gastric tumors were
      performed and the integration resulted in the identification of three categories
      of factors/pathways: i) highly activated signaling pathways that stem from
      mutations are the critical oncogenic drivers, ii) constitutively activated stress
      responsive pathways which are activated not due to genetic alterations, and iii)
      consistently down-regulated nuclear receptor responsive factors. This functional
      profiling helps in discriminating therapeutic targets and signaling interactions.

PMID- 24462707
TI  - microRNA-383 impairs phosphorylation of H2AX by targeting PNUTS and inducing cell
      cycle arrest in testicular embryonal carcinoma cells.
AB  - Male germ cells with aberrant DNA damage are the weighted factor contributing to
      male infertility. Mounting evidence shows that DNA damage in male germ cells
      impairs spermatogenesis and lowers fecundity. MicroRNAs (miRNAs) regulating
      expression of multiple genes play a significant role in spermatogenesis. Our
      previous results have shown that microRNA-383 (miR-383) is one of the notable
      down-regulated microRNAs in the testes of sterile males with maturation arrest
      (MA) and is located predominantly in spermatogonia and primary spermatocytes.
      However, the role that miR-383 plays in DNA damage during spermatogenesis remains
      unknown. In this study, we found that miR-383 inhibited the focal formation and
      abundance of gammaH2AX, which is the major marker of sites of DNA damage, with or
      without ultraviolet irradiation and cisplatin in testicular embryonal carcinoma
      (NT-2) cells. In addition, NT-2 cells were remarkably sensitized to DNA damage
      reagent (cisplatin) by forcing expression of miR-383 and silencing expression of
      protein phosphatase 1, regulatory subunit 10 (PNUTS). By constructing Renilla
      luciferase reporters and co-transfecting miR-383 and reporters in NT-2 cells, we
      identified that PNUTS was a valid target of miR-383. Further results demonstrated
      that the repression of the phosphorylated form of H2AX by miR-383 was due to
      independent depletion of PNUTS and cell cycle arrest. In conclusion, we found a
      novel function of miR-383 in the DNA damage pathway. miR-383 impairs the
      phosphorylation of H2AX by targeting PNUTS and inducing cell cycle arrest
      independently, as well as sensitizing NT-2 cells to cisplatin. 

PMID- 24462709
TI  - Platelet-derived growth factor-stimulated versican synthesis but not
      glycosaminoglycan elongation in vascular smooth muscle is mediated via Akt
      phosphorylation.
AB  - Proteoglycans are associated with the initiation of atherosclerosis due to their
      binding of apolipoproteins on lipid particles leading to retention in the vessel
      wall. The signaling pathways through which growth factors regulate the synthesis
      and structure of proteoglycans are potential therapeutic targets. Platelet
      derived growth factor (PDGF) is present in atherosclerotic plaques and activates
      phosphorylation of the serine/threonine kinase Akt. We have investigated the role
      of Akt in the signaling pathways for proteoglycan core protein expression and
      elongation of glycosaminoglycan chains on proteoglycans secreted by human
      vascular smooth muscle cells. The pharmacological inhibitor of Akt
      phosphorylation, SN30978, blocked PDGF stimulated phosphorylation of Akt. SN30978
      caused concentration dependent inhibition of PDGF stimulated radiosulfate
      incorporation into secreted proteoglycans and the response was blocked by the
      PDGF receptor antagonists Ki11502 and imatinib. Analysis of the size of the
      biglycan molecules by SDS-PAGE showed that PDGF increased the apparent size of
      biglycan but this effect on glycosaminoglycan chain elongation was blocked by
      Ki11502 but not by SN30978. PDGF also stimulated total protein core protein
      synthesis assessed as (35)S-methionine/cysteine incorporation and specifically
      the expression of versican mRNA. Both of these responses were blocked by SN30978.
      This data shows that PDGF-stimulated proteoglycan core protein synthesis but not
      glycosaminoglycan chain elongation is mediated via Akt phosphorylation. These
      data identify potential pathways for the development of agents which can
      pharmacologically regulate individual components of the synthesis of
      proteoglycans. 

PMID- 24462708
TI  - Ezrin expression and cell survival regulation in colorectal cancer.
AB  - Colorectal cancer (CRC) is the second largest cause of cancer deaths in the
      United States. A key barrier that prevents better outcomes for this type of
      cancer as well as other solid tumors is the lack of effective therapies against
      the metastatic disease. Thus there is an urgent need to fill this gap in cancer
      therapy. We utilized a 2D-DIGE proteomics approach to identify and characterize
      proteins that are differentially regulated between primary colon tumor and liver
      metastatic deposits of the IGF1R-dependent GEO human CRC xenograft,
      orthotopically implanted in athymic nude mice that may serve as potential
      therapeutic targets against CRC metastasis. We observed increased expression of
      ezrin in liver metastasis in comparison to the primary colonic tumor. Increased
      ezrin expression was further confirmed by western blot and microarray analyses.
      Ezrin, a cytoskeletal protein belonging to Ezrin-Radixin-Moesin (ERM) family
      plays important roles in cell motility, invasion and metastasis. However, its
      exact function in colorectal cancer is not well characterized. Establishment of
      advanced GEO cell lines with enhanced liver-metastasizing ability showed a
      significant increase in ezrin expression in liver metastasis. Increased
      phosphorylation of ezrin at the T567 site (termed here as p-ezrin T567) was
      observed in liver metastasis. IHC studies of human CRC patient specimens showed
      an increased expression of p-ezrin T567 in liver metastasis compared to the
      primary tumors of the same patient. Ezrin modulation by siRNA, inhibitors and
      T567A/D point mutations significantly downregulated inhibitors of apoptosis (IAP)
      proteins XIAP and survivin that have been linked to increased aberrant cell
      survival and metastasis and increased cell death. Inhibition of the IGF1R
      signaling pathway by humanized recombinant IGF1R monoclonal antibody MK-0646 in
      athymic mouse subcutaneous xenografts resulted in inhibition of p-ezrin T567
      indicating ezrin signaling is downstream of the IGF1R signaling pathway. We
      identified increased expression of p-ezrin T567 in CRC liver metastasis in both
      orthotopically implanted GEO tumors as well as human patient specimens. We report
      for the first time that p-ezrin T567 is downstream of the IGF1R signaling and
      demonstrate that ezrin regulates cell survival through survivin/XIAP modulation. 

PMID- 24462710
TI  - Resurgence in Siamese fighting fish, Betta splendens.
AB  - Resurgence of previously reinforced responding was investigated in male Siamese
      fighting fish (Betta splendens). Swimming through a ring produced 15-s mirror
      presentations according to, with different fish, either a fixed-ratio 1 or a
      variable-interval 60-s schedule of reinforcement. When responding was stable, a
      differential-reinforcement-of-other-behavior schedule was substituted for the
      mirror-presentation schedule. Following this, mirror presentations were
      discontinued (extinction). During this latter phase, there were transient
      increases in the ring-swim response relative to the frequency of such responding
      during the differential-reinforcement-of-other behavior schedule. Resurgence was
      similar for the fish exposed previously to the fixed-ratio or to the variable
      interval schedule. These results extend to Siamese fighting fish a well
      established behavioral phenomenon previously not observed in this species or with
      this response topography, and only rarely reported following the removal of a non
      consumable reinforcer. 

PMID- 24462711
TI  - Mitochondrial iron-sulfur protein biogenesis and human disease.
AB  - Work during the past 14 years has shown that mitochondria are the primary site
      for the biosynthesis of iron-sulfur (Fe/S) clusters. In fact, it is this process
      that renders mitochondria essential for viability of virtually all eukaryotes,
      because they participate in the synthesis of the Fe/S clusters of key nuclear and
      cytosolic proteins such as DNA polymerases, DNA helicases, and ABCE1 (Rli1), an
      ATPase involved in protein synthesis. As a consequence, mitochondrial function is
      crucial for nuclear DNA synthesis and repair, ribosomal protein synthesis, and
      numerous other extra-mitochondrial pathways including nucleotide metabolism and
      cellular iron regulation. Within mitochondria, the synthesis of Fe/S clusters and
      their insertion into apoproteins is assisted by 17 proteins forming the ISC (iron
      sulfur cluster) assembly machinery. Biogenesis of mitochondrial Fe/S proteins can
      be dissected into three main steps: First, a Fe/S cluster is generated de novo on
      a scaffold protein. Second, the Fe/S cluster is dislocated from the scaffold and
      transiently bound to transfer proteins. Third, the latter components, together
      with specific ISC targeting factors insert the Fe/S cluster into client
      apoproteins. Disturbances of the first two steps impair the maturation of extra
      mitochondrial Fe/S proteins and affect cellular and systemic iron homeostasis. In
      line with the essential function of mitochondria, genetic mutations in a number
      of ISC genes lead to severe neurological, hematological and metabolic diseases,
      often with a fatal outcome in early childhood. In this review we briefly
      summarize our current functional knowledge on the ISC assembly machinery, and we
      present a comprehensive overview of the various Fe/S protein assembly diseases. 

PMID- 24462712
TI  - Traditional difference-score analyses of reasoning are flawed.
AB  - Studies of the belief bias effect in syllogistic reasoning have relied on three
      traditional difference score measures: the logic index, belief index, and
      interaction index. Dube, Rotello, and Heit (2010, 2011) argued that the
      interaction index incorrectly assumes a linear receiver operating characteristic
      (ROC). Here, all three measures are addressed. Simulations indicated that
      traditional analyses of reasoning experiments are likely to lead to incorrect
      conclusions. Two new experiments examined the role of instructional manipulations
      on the belief bias effect. The form of the ROCs violated assumptions of
      traditional measures. In comparison, signal detection theory (SDT) model-based
      analyses were a better match for the form of the ROCs, and implied that belief
      bias and instructional manipulations are predominantly response bias effects.
      Finally, reanalyses of previous studies of conditional reasoning also showed non
      linear ROCs, violating assumptions of traditional analyses. Overall, reasoning
      research using traditional measures is at risk of drawing incorrect conclusions. 

PMID- 24462713
TI  - Brief non-symbolic, approximate number practice enhances subsequent exact
      symbolic arithmetic in children.
AB  - Recent research reveals a link between individual differences in mathematics
      achievement and performance on tasks that activate the approximate number system
      (ANS): a primitive cognitive system shared by diverse animal species and by
      humans of all ages. Here we used a brief experimental paradigm to test one causal
      hypothesis suggested by this relationship: activation of the ANS may enhance
      children's performance of symbolic arithmetic. Over 2 experiments, children who
      briefly practiced tasks that engaged primitive approximate numerical quantities
      performed better on subsequent exact, symbolic arithmetic problems than did
      children given other tasks involving comparison and manipulation of non-numerical
      magnitudes (brightness and length). The practice effect appeared specific to
      mathematics, as no differences between groups were observed on a comparable
      sentence completion task. These results move beyond correlational research and
      provide evidence that the exercise of non-symbolic numerical processes can
      enhance children's performance of symbolic mathematics. 

PMID- 24462714
TI  - Pathway-based analysis of the hidden genetic heterogeneities in cancers.
AB  - Many cancers apparently showing similar phenotypes are actually distinct at the
      molecular level, leading to very different responses to the same treatment. It
      has been recently demonstrated that pathway-based approaches are robust and
      reliable for genetic analysis of cancers. Nevertheless, it remains unclear
      whether such function-based approaches are useful in deciphering molecular
      heterogeneities in cancers. Therefore, we aimed to test this possibility in the
      present study. First, we used a NCI60 dataset to validate the ability of pathways
      to correctly partition samples. Next, we applied the proposed method to identify
      the hidden subtypes in diffuse large B-cell lymphoma (DLBCL). Finally, the
      clinical significance of the identified subtypes was verified using survival
      analysis. For the NCI60 dataset, we achieved highly accurate partitions that best
      fit the clinical cancer phenotypes. Subsequently, for a DLBCL dataset, we
      identified three hidden subtypes that showed very different 10-year overall
      survival rates (90%, 46% and 20%) and were highly significantly (P=0.008)
      correlated with the clinical survival rate. This study demonstrated that the
      pathway-based approach is promising for unveiling genetic heterogeneities in
      complex human diseases. 

PMID- 24462715
TI  - Retrotransposon "Qian" mediated segmental duplication in silkworm, Bombyx mori.
AB  - Transposable elements constitute a large fraction of the eukaryotic genomes. They
      have the potential to alter genome structure and play a major role in genome
      evolution. Here, we report a segmental duplication mediated by a novel long
      terminal repeat (LTR) retrotransposon as the cause of an egg-shell recessive
      lethal mutant (l-em mutant) in silkworm (Bombyx mori). The segmental duplication
      resulted in the duplication of six genes and the disruption of two genes.
      Disruption of BmEP80 (B. mori egg protein 80), a gene encoding a major egg-shell
      structure protein, is likely responsible for the lethal water-loss phenotype in
      the l-em/l-em mutant. Our data revealed that BmEP80 is present in the inner egg
      shell layer and plays important roles in resistance to water efflux form eggs. A
      novel LTR retrotransposon (named as "Qian") was identified and the model for the
      Qian-mediated chromosomal segmental duplication was proposed. Detail biochemical
      and genomic analyses on the l-em mutant offer an opportunity to demonstrate that
      an LTR retrotransposon could trigger duplication of a chromosomal segment (~96.3
      kb) and confer novel phenotype.

PMID- 24462716
TI  - Effect of L-amino acid oxidase from Calloselasma rhodosthoma snake venom on human
      neutrophils.
AB  - The in vitro effects of LAAO, an l-amino acid oxidase isolated from Calloselasma
      rhodosthoma snake venom, on isolated human neutrophil function were investigated.
      LAAO showed no toxicity on neutrophils. At non-cytotoxic concentrations, LAAO
      induced the superoxide anion production by isolated human neutrophil. This toxin,
      in its native form, is also able to stimulate the production of hydrogen peroxide
      in neutrophils, suggesting that its primary structure is essential for
      stimulation the cell. Moreover, the incubation of LAAO and phenol red medium did
      not induce the production of hydrogen peroxide. Furthermore, LAAO was able to
      stimulate neutrophils to release proinflammatory mediators such as IL-8 and TNF
      alpha as well as NETs liberation. Together, the data showed that the LAAO
      triggers relevant proinflammatory events. Particular regions of the molecule
      distinct from the LAAO catalytic site may be involved in the onset of
      inflammatory events. 

PMID- 24462717
TI  - Microcystin-LR affects properties of human epidermal skin cells crucial for
      regenerative processes.
AB  - The occurrence of cyanobacterial toxic peptides, including microcystins (MCs), is
      an emerging health issue due to the eutrophication of water bodies. MCs have a
      strong influence on human cells, predominantly hepatocytes, however, toxicity was
      also observed in kidney, lung and dermal skin cells. Skin as the most external
      barrier of the human body is responsible for the maintenance of homeostasis of
      the whole organism. Simultaneously, skin cells may be the most exposed to MCs
      during recreational activity. The aim of this study was to examine the impact of
      MC-LR on processes indispensable for normal skin function and regeneration,
      namely, viability, migration and actin cytoskeleton organization of human
      keratinocytes. The results showed that short exposure to MC-LR does not affect
      proliferation of human skin keratinocytes but it is toxic after longer incubation
      in dose-dependent manner. Total disruption of the actin cytoskeleton was observed
      under the same MC-LR concentration. Furthermore, keratinocyte migration was
      inhibited at MC-LR concentrations of 50 MUM after incubation for only 4 h. Some
      of the negative impacts of MC-LR on the examined cell processes may be partly
      reversible. The observed effects, regarding the possible high exposition of
      keratinocytes to toxins including MCs, are severe and may cause diverse health
      problems. 

PMID- 24462718
TI  - Semantic congruence reverses effects of sleep restriction on associative
      encoding.
AB  - Encoding and memory consolidation are influenced by factors such as sleep and
      congruency of newly learned information with prior knowledge (i.e., schema).
      However, only a few studies have examined the contribution of sleep to
      enhancement of schema-dependent memory. Based on previous studies showing that
      total sleep deprivation specifically impairs hippocampal encoding, and that
      coherent schemas reduce the hippocampal consolidation period after learning, we
      predict that sleep loss in the pre-training night will mainly affect schema
      unrelated information whereas sleep restriction in the post-training night will
      have similar effects on schema-related and unrelated information. Here, we tested
      this hypothesis by presenting participants with face-face associations that could
      be semantically related or unrelated under different sleep conditions: normal
      sleep before and after training, and acute sleep restriction either before or
      after training. Memory was tested one day after training, just after introducing
      an interference task, and two days later, without any interference. Significant
      results were evident on the second retesting session. In particular, sleep
      restriction before training enhanced memory for semantically congruent events in
      detriment of memory for unrelated events, supporting the specific role of sleep
      in hippocampal memory encoding. Unexpectedly, sleep restriction after training
      enhanced memory for both related and unrelated events. Although this finding may
      suggest a poorer encoding during the interference task, this hypothesis should be
      specifically tested in future experiments. All together, the present results
      support a framework in which encoding processes seem to be more vulnerable to
      sleep loss than consolidation processes. 

PMID- 24462719
TI  - Investigating the effects of musical training on functional brain development
      with a novel Melodic MMN paradigm.
AB  - Sensitivity to changes in various musical features was investigated by recording
      the mismatch negativity (MMN) auditory event-related potential (ERP) in musically
      trained and nontrained children semi-longitudinally at the ages of 9, 11, and 13
      years. The responses were recorded using a novel Melodic multi-feature paradigm
      which allows fast (<15 min) recording of an MMN profile for changes in melody,
      rhythm, musical key, timbre, tuning and timing. When compared to the nontrained
      children, the musically trained children displayed enlarged MMNs for the melody
      modulations by the age 13 and for the rhythm modulations, timbre deviants and
      slightly mistuned tones already at the age of 11. Also, a positive mismatch
      response elicited by delayed tones was larger in amplitude in the musically
      trained than in the nontrained children at age 13. No group differences were
      found at the age 9 suggesting that the later enhancement of the MMN in the
      musically trained children resulted from training and not pre-existing difference
      between the groups. The current study demonstrates the applicability of the
      Melodic multi-feature paradigm in school-aged children and indicates that musical
      training enhances auditory discrimination for musically central sound dimensions
      in pre-adolescence.

PMID- 24462720
TI  - Reduced activity-dependent protein levels in a mouse model of the fragile X
      premutation.
AB  - Environmental enrichment results in increased levels of Fmrp in brain and
      increased dendritic complexity. The present experiment evaluated activity
      dependent increases in Fmrp levels in the motor cortex in response to training on
      a skilled forelimb reaching task in the CGG KI mouse model of the fragile X
      premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot
      in the contralateral motor cortex of mice following training to reach for sucrose
      pellets with a non-preferred paw and compared to levels in the ipsilateral motor
      cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein
      levels in the contralateral compared to the ipsilateral hemisphere; however, the
      increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc
      proteins scaled with learning, whereas this relationship was not observed with
      the c-Fos levels. These data suggest the possibility that reduced levels of
      activity-dependent proteins associated with synaptic plasticity such as Fmrp and
      Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice
      and the fragile X premutation. 

PMID- 24462721
TI  - Different roles for M1 and M2 receptors within perirhinal cortex in object
      recognition and discrimination.
AB  - Recognition and discrimination of objects and individuals are critical cognitive
      faculties in both humans and non-human animals, and cholinergic transmission has
      been shown to be essential for both of these functions. In the present study we
      focused on the role of M1 and M2 muscarinic receptors in perirhinal cortex (PRh)
      dependent object recognition and discrimination. The selective M1 antagonists
      pirenzepine and the snake toxin MT-7, and a selective M2 antagonist, AF-DX 116,
      were infused directly into PRh. Pre-sample infusions of both pirenzepine and AF
      DX 116 significantly impaired object recognition memory in a delay-dependent
      manner. However, pirenzepine and MT-7, but not AF-DX 116, impaired oddity
      discrimination performance in a perceptual difficulty-dependent manner. The
      findings indicate distinct functions for M1 and M2 receptors in object
      recognition and discrimination. 

PMID- 24462723
TI  - Oral tolerance can be established via gap junction transfer of fed antigens from
      CX3CR1+ macrophages to CD103+ dendritic cells.
AB  - Antigen-presenting cells (APCs) in the gut are apt at oral tolerance
      establishment at steady state and immunity after infection; complex tasks in an
      environment exposed to the inflammatory burden of the microbiota. Here we show an
      unanticipated division of labor among APCs for the establishment of oral
      tolerance. Chemokine receptor CX3CR1(+) macrophages were found to take up soluble
      fed antigens and quickly transfer them to CD103(+) dendritic cells (DCs). Antigen
      transfer occurred via a mechanism that was Connexin 43-dependent and required
      membrane transfer, indicating a physiological role of gap junctions in antigen
      presentation. Deletion of Connexin 43 in APCs affected antigen transfer and
      resulted in the inability of CD103(+) DCs to acquire and present antigens in
      vivo, to drive T regulatory cell differentiation and to induce tolerance to food
      antigens. This functional cooperation between intestinal phagocytes might be a
      mechanism to avoid the exposure of tolerogenic DCs to the intestinal microbiota.

PMID- 24462722
TI  - Two types of transgenic lines for doxycycline-inducible, cell-specific gene
      expression in zebrafish ultraviolet cone photoreceptors.
AB  - Temporal and spatial control of gene expression is important for studying the
      molecular and cellular mechanisms of development, physiology, and disease. We
      used the doxycycline (Dox)-inducible, Tet-On system to develop transgenic
      zebrafish for inducible, cell specific control of gene expression in the
      ultraviolet (UV) cone photoreceptors. Two constructs containing the reverse
      tetracycline-controlled transcriptional transactivator (rtTA) gene driven by the
      UV opsin-specific promoter (opn1sw1) were used to generate stable transgenic
      zebrafish lines using the Tol2-based transgenesis method. One construct included
      a self-reporting GFP (opn1sw1:rtTA, TRE:GFP) and the other incorporated an
      epitope tag on the rtTA protein (opn1sw1:rtTA(flag)). UV cone-specific expression
      of TRE-controlled transgenes was induced by Dox treatment in larvae and adults.
      Induction of gene expression was observed in 96% of all larval UV cones within 16
      h of Dox treatment. UV cone-specific expression of two genes from a bidirectional
      TRE construct injected into one-cell Tg(opn1sw1:rtTA(flag)) embryos were also
      induced by Dox treatment. In addition, UV cone-specific expression of
      Crb2a(IntraWT) was induced by Dox treatment in progeny from crosses of the TRE
      response transgenic line, Tg(TRE:HA-Crb2a(IntraWT)), to the Tg(opn1sw1:rtTA,
      TRE:GFP) line and the Tg(opn1sw1:rtTA(flag)) line. These lines can be used in
      addition to the inducible, rod-specific gene expression system from the Tet-On
      Toolkit to elucidate the photoreceptor-specific effects of genes of interest in
      photoreceptor cell biology and retinal disease.

PMID- 24462726
TI  - Long-term behavioral effects of neonatal blockade of gastrin-releasing peptide
      receptors in rats: similarities to autism spectrum disorders.
AB  - Gastrin releasing peptide, the mammalian counterpart of the amphibian peptide,
      bombesin, has been increasingly implicated in regulating normal brain function as
      well as in the pathogenesis of psychiatric and/or neurodevelopmental disorders.
      We have previously shown that the neonatal blockade of the gastrin-releasing
      peptide receptor (GRPr) in rats produces long-lasting consequences during central
      nervous system development that are commonly observed in neurodevelopmental
      disorders such as autism spectrum disorders. The present investigation assessed
      in further detail, long-term behavioral effects of neonatal GRPr blockade. During
      postnatal days 1-10, male Wistar rat pups (n=5-10/litter) were injected
      (subcutaneously) with the GRPr antagonist, RC-3095 (1 mg/kg), or a vehicle
      (control), twice daily. Following the drug treatment regimen, several behaviors
      were assessed (starting on postnatal day 14) including specific social behaviors
      (namely, group huddling characteristics, social interaction, and social
      approach), restrictive/repetitive and stereotyped behaviors (y-maze, repetitive
      novel object contact task, observation for stereotypies) and anxiety/fear-related
      responses (open field, elevated plus maze and contextual fear conditioning). Rats
      treated neonatally with RC-3095 showed reduced sociability, restrictive
      interests, motor stereotypies and enhanced learned fear response compared to the
      controls (vehicle-treated rats). These behavioral abnormalities are consistent
      with those observed in autism spectrum disorders and provide further evidence
      that neonatal blockade of GRPr could potentially serve as a useful model to gain
      a better understanding of the underlying neurodevelopmental disruptions
      contributing to the expression of autism-relevant phenotypes.

PMID- 24462725
TI  - Hippocampal biomarkers of fear memory in an animal model of generalized anxiety
      disorder.
AB  - Generalized anxiety disorder (GAD) is highly prevalent and incapacitating. Here
      we used the Carioca High-Conditioned Freezing (CHF) rats, a previously validated
      animal model for GAD, to identify biomarkers and structural changes in the
      hippocampus that could be part of the underlying mechanisms of their high-anxiety
      profile. Spatial and fear memory was assessed in the Morris water maze and
      passive avoidance test. Serum corticosterone levels, immunofluorescence for
      glucocorticoid receptors (GR) in the dentate gyrus (DG), and western blotting for
      hippocampal brain derived neurotrophic factor (BDNF) were performed.
      Immunohistochemistry for markers of cell proliferation (bromodeoxiuridine/Ki-67),
      neuroblasts (doublecortin), and cell survival were undertaken in the DG, along
      with spine staining (Golgi) and dendritic arborization tracing. Hippocampal GABA
      release was assessed by neurochemical assay. Fear memory was higher among CHF
      rats whilst spatial learning was preserved. Serum corticosterone levels were
      increased, with decreased GR expression. No differences were observed in
      hippocampal cell proliferation/survival, but the number of newborn neurons was
      decreased, along with their number and length of tertiary dendrites. Increased
      expression of proBDNF and dendritic spines was observed; lower ratio of GABA
      release in the hippocampus was also verified. These findings suggest that
      generalized anxiety/fear could be associated with different hippocampal
      biomarkers, such as increased spine density, possibly as a compensatory mechanism
      for the decreased hippocampal number of neuroblasts and dendritic arborization
      triggered by high corticosterone. Disruption of GABAergic signaling and BDNF
      impairment are also proposed as part of the hippocampal mechanisms possibly
      underlying the anxious phenotype of this model. 

PMID- 24462727
TI  - Overexpression of the dopamine D3 receptor in the rat dorsal striatum induces
      dyskinetic behaviors.
AB  - L-DOPA-induced dyskinesias (LID) are motor side effects associated with treatment
      of Parkinson's disease (PD). The etiology of LID is not clear; however, studies
      have shown that the dopamine D3 receptor is upregulated in the basal ganglia of
      mice, rats and non-human primate models of LID. It is not known if the
      upregulation of D3 receptor is a cause or result of LID. In this paper we tested
      the hypothesis that overexpression of the dopamine D3 receptor in dorsal
      striatum, in the absence of dopamine depletion, will elicit LID. Replication
      deficient recombinant adeno-associated virus-2 expressing the D3 receptor or
      enhanced green fluorescent protein (EGFP) were stereotaxically injected,
      unilaterally, into the dorsal striatum of adult rats. Post-hoc
      immunohistochemical analysis revealed that ectopic expression of the D3 receptor
      was limited to neurons near the injection sites in the dorsal striatum. Following
      a 3-week recovery period, rats were administered saline, 6 mg/kg L-DOPA, 0.1
      mg/kg PD128907 or 10 mg/kg ES609, i.p., and motor behaviors scored. Rats
      overexpressing the D3 receptor specifically exhibited contralateral axial
      abnormal involuntary movements (AIMs) following administration of L-DOPA and
      PD128907 but not saline or the novel agonist ES609. Daily injection of 6 mg/kg L
      DOPA to the rats overexpressing the D3 receptor also caused increased vacuous
      chewing behavior. These results suggest that overexpression of the D3 receptor in
      the dorsal striatum results in the acute expression of agonist-induced axial AIMs
      and chronic L-DOPA-induced vacuous chewing behavior. Agonists such as ES609 might
      provide a novel therapeutic approach to treat dyskinesia.

PMID- 24462729
TI  - Lack of association between breast reconstructive surgery and the development of
      chronic pain after mastectomy: a propensity matched retrospective cohort
      analysis.
AB  - OBJECTIVES: To compare if mastectomy with reconstructive surgery had greater
      incidence of chronic pain compared to mastectomy surgery alone. MATERIALS AND
      METHODS: The study was a retrospective cohort. Patients who underwent
      mastectomies with and without reconstruction responded to the modified short form
      Brief Pain Inventory and the short form McGill pain questionnaire to identify and
      characterize pain at least 6 months after the surgical procedure. Propensity
      matching analysis was used to control for covariates differences in the study
      groups. RESULTS: 310 subjects were included and 132 patients (43%) reported the
      presence of chronic pain. After propensity score matching to adjust for covariate
      imbalances, the incidence of chronic pain in the mastectomy group who had
      additional surgery for breast reconstruction was not different compared to the
      group who had mastectomy surgery alone, 26 out of 68 (38%) and 27 out of 68
      (39%), respectively P = 1.0. Among patients who had chronic pain, breast
      reconstruction did not increase the intensity of worst pain in the last 24 h,
      median (IQR) of 2 (1-5) compared to 4 (1-5) in the no reconstruction group, P =
      0.41. Type of reconstruction (breast implants vs. flap tissue) did not result in
      greater incidence and/or intensity of chronic pain. CONCLUSIONS: Breast
      reconstruction after mastectomy does not result in a greater incidence of chronic
      pain compared to mastectomy alone. Female patients undergoing breast cancer
      surgery should not incorporate chronic pain in their decision to undergo
      reconstructive surgery after mastectomy.

PMID- 24462728
TI  - High frequency stimulation of subthalamic nucleus results in behavioral recovery
      by increasing striatal dopamine release in 6-hydroxydopamine lesioned rat.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective
      medical therapy in alleviating motor symptoms in moderate to severe Parkinson's
      disease (PD) patients. However, there are still remaining questions regarding the
      mechanisms of this action. In this experiment, using 6-hydroxydopamine (6-OHDA)
      PD rat model we investigated the effect of high frequency stimulation (HFS)-STN
      on improvement of the motor symptoms, DA release in the striatum and to elucidate
      the underlying mechanisms. Our results showed that HFS-STN improved the motor
      symptoms of 6-OHDA lesioned rat model of PD via inducing a significant increase
      in the extracellular dopamine levels and directly evoked dopamine release in the
      striatum of normal and partially 6-OHDA lesioned rats. In addition, we found the
      tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta
      (SNpc) did not increase after HFS-STN, while the expression of TH in the
      substantia nigra increased significantly compared to the 6-OHDA lesioned group.
      This suggested that STN-HFS could reverse motor deficits against 6-OHDA-induced
      lesion through increasing striatal dopamine release by modulating the expression
      of TH, without rescuing dopaminergic neurons in the SNpc. 

PMID- 24462730
TI  - Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in
      ovarian cancer.
AB  - OBJECTIVE: To investigate the neutrophil-to-lymphocyte ratio (NLR) from
      peripheral blood, a general measure of inflammation, in ovarian cancer. METHODS:
      White cell counts and CA125 levels before treatment, tumor features, and
      questionnaire data on 519 women with ovarian cancer at two Boston hospitals were
      recorded. Counts were log-transformed and effects on these by tumor features and
      epidemiologic variables assessed by analysis of variance and generalized linear
      models. Cox proportional hazards models were used to assess effects on overall
      survival. RESULTS: Greater NLR was associated with higher tumor stage and grade,
      presence of ascites, and bilateral disease and correlated with risk factors
      including Jewish ethnicity, taller height, more ovulatory cycles, and family
      history of cancer in premenopausal women and talc use in all women. CA125 was
      positively correlated with neutrophil count, monocyte count, and NLR and
      inversely correlated with lymphocyte count. In a multivariate adjusted analysis,
      high NLR predicted poorer survival and high lymphocyte count better survival.
      CONCLUSION: An elevated NLR before treatment signals more aggressive disease and
      correlates with risk factors for ovarian cancer. CA125 directly correlates with
      neutrophils which may reflect secretion of both CA125 and neutrophilic growth
      factors by the tumor. CA125 inversely correlates with lymphocytes which may
      reflect the ability of some neutrophilic factors to induce lymphopenia and/or
      binding of CA125 to lymphocytes removing CA125 from the serum pool. Links between
      NLR, CA125, and epidemiologic factors may provide new clues about the
      pathogenesis and progression of ovarian cancer.

PMID- 24462731
TI  - An exploratory investigation of links between changes in adipokines and quality
      of life in individuals undergoing weight loss interventions: possible
      implications for cancer research.
AB  - OBJECTIVE: Obesity has been linked to a wide spectrum of malignancies, with the
      strongest association demonstrated for endometrial cancer. Although the
      mechanisms are not yet entirely clear, a number of risk biomarkers have been
      proposed, including altered adipokines. Systemic levels of these adipose derived
      molecules have also been linked in prior research to self-reported quality of
      life (QOL). The study objective was to examine the hypothesis that adipokine
      changes during intentional weight loss may be associated with changes in QOL.
      METHODS: Fifty-two female participants were selected from two behavioral weight
      loss trials (SMART and PREFER) on the basis of achieving successful weight loss
      at 6month assessment, availability of blood samples and completion of standard SF
      36 QOL questionnaires. Levels of adiponectin, leptin, and resistin were measured
      using xMAP immunoassays. Changes in QOL were examined using linear regression
      models in relation to pre- and post-intervention changes in biomarker levels and
      BMI. RESULTS: Significant changes between pre- and post-intervention were
      observed for leptin. Controlling for baseline BMI, leptin was the only biomarker
      that predicted change in QOL (Physical Component Scale, PCS). Linear regression
      models demonstrated that leptin continued to be a significant predictor of change
      in PCS when other possible predictor variables were included in the model.
      CONCLUSIONS: This study is among the first to demonstrate that changes in PCS may
      be regulated by levels of both metabolic variables and adipokines. An improved
      understanding of biological mechanisms associated with weight loss and the role
      of QOL may help guide preventive strategies for obesity-associated cancers.

PMID- 24462732
TI  - Prognostic and predictive value of the Arbeitsgemeinschaft Gynaekologische
      Onkologie (AGO) score in surgery for recurrent ovarian cancer.
AB  - OBJECTIVES: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score was
      developed as selection criteria and validated as predictor of a high probability
      for complete resection in recurrent ovarian cancer. It is not defined whether the
      predictive value is independent from underlying tumor biology or is solely based
      on a selection of good prognostic risks. METHODS: We performed an exploratory
      analysis of all consecutive patients with cytoreductive surgery in recurrent
      ovarian cancer in a tertiary referral center 1999-2013, before and after
      introduction of the AGO score. RESULTS: 217 consecutive patients were included of
      whom 112 patients were AGO score positive and 105 patients were score negative.
      Corresponding complete resection rates were 89.3% and 66.7%, respectively, and
      confirm the score's predictive value. However, a positive AGO score was also
      associated with better outcome after adjustment for surgical outcome. Patients
      with complete resection and a positive AGO score showed a median overall survival
      of 63.9 months (95% CI 48.1-79.6) compared to 48.4 months (95% CI 30.3-66.5)
      after complete resection and negative score (log-rank p=0.10). However, in
      multivariate analysis the only independent prognostic factor was complete
      resection (HR 2.450; 95% CI: 1.542-3.891). CONCLUSIONS: The AGO score could
      identify suitable candidates for secondary cytoreductive surgery but failed to
      prove an independent prognostic value thus suggesting an effect of successful
      surgery on its own. However, the latter has to be proven prospectively. In
      addition, further studies should evaluate the predictive and prognostic impact of
      a negative score.

PMID- 24462733
TI  - A new laboratory-based algorithm to predict development of hepatocellular
      carcinoma in patients with hepatitis C and cirrhosis.
AB  - BACKGROUND & AIMS: Serum levels of alpha-fetoprotein (AFP) are influenced not
      only by the presence of hepatocellular carcinoma (HCC), but also by the
      underlying severity and activity of liver disease, which is reflected by liver
      function tests. We constructed an AFP-based algorithm that included these factors
      to identify patients at risk for HCC, and tested its predictive ability in a
      large set of patients with cirrhosis. METHODS: We used the national Department of
      Veterans Affairs Hepatitis C Virus Clinical Case Registry to identify patients
      with cirrhosis, results from at least 1 AFP test, and 6 months of follow-up. Our
      algorithm included data on age; levels of aspartate aminotransferase, alanine
      aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin,
      creatinine, and hemoglobin; prothrombin time; and numbers of platelets and white
      cells. We examined the operating characteristics (calibration, discrimination,
      predictive values) of several different algorithms for identification of patients
      who would develop HCC within 6 months of the AFP test. We assessed our final
      model in the development and validation subsets. RESULTS: We identified 11,721
      patients with hepatitis C virus-related cirrhosis in whom 35,494 AFP tests were
      performed, and 987 patients developed HCC. A predictive model that included data
      on levels of AFP, ALT, and platelets, along with age at time of AFP test (and
      interaction terms between AFP and ALT, and AFP and platelets), best discriminated
      between patients who did and did not develop HCC. Using this AFP-adjusted model,
      the predictive accuracy increased at different AFP cutoffs compared with AFP
      alone. At any given AFP value, low numbers of platelets and ALT and older age
      were associated with increased risk of HCC, and high levels of ALT and
      normal/high numbers of platelets were associated with low risk for HCC. For
      example, the probabilities of HCC, based only on 20 ng/mL and 120 ng/mL AFP, were
      3.5% and 11.4%, respectively. However, patients with the same AFP values (20
      ng/mL and 120 ng/mL) who were 70 years old, with ALT levels of 40 IU/mL and
      platelet counts of 100,000, had probabilities of developing HCC of 8.1% and
      29.0%, respectively. CONCLUSIONS: We developed and validated an algorithm based
      on levels of AFP, platelets, and ALT, along with age, which increased the
      predictive value for identifying patients with hepatitis C virus-associated
      cirrhosis likely to develop HCC within 6 months. If validated in other patient
      groups, this model would have immediate clinical applicability.

PMID- 24462734
TI  - Fascin is regulated by slug, promotes progression of pancreatic cancer in mice,
      and is associated with patient outcomes.
AB  - BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often lethal
      because it is highly invasive and metastasizes rapidly. The actin-bundling
      protein fascin has been identified as a biomarker of invasive and advanced PDAC
      and regulates cell migration and invasion in vitro. We investigated fascin
      expression and its role in PDAC progression in mice. METHODS: We used KRas(G12D)
      p53(R172H) Pdx1-Cre (KPC) mice to investigate the effects of fascin deficiency on
      development of pancreatic intraepithelial neoplasia (PanIn), PDAC, and
      metastasis. We measured levels of fascin in PDAC cell lines and 122 human
      resected PDAC samples, along with normal ductal and acinar tissues; we associated
      levels with patient outcomes. RESULTS: Pancreatic ducts and acini from control
      mice and early-stage PanINs from KPC mice were negative for fascin, but
      approximately 6% of PanIN3 and 100% of PDAC expressed fascin. Fascin-deficient
      KRas(G12D) p53(R172H) Pdx1-Cre mice had longer survival times, delayed onset of
      PDAC, and a lower PDAC tumor burdens than KPC mice; loss of fascin did not affect
      invasion of PDAC into bowel or peritoneum in mice. Levels of slug and fascin
      correlated in PDAC cells; slug was found to regulate transcription of Fascin
      along with the epithelial-mesenchymal transition. In PDAC cell lines and cells
      from mice, fascin concentrated in filopodia and was required for their assembly
      and turnover. Fascin promoted intercalation of filopodia into mesothelial cell
      layers and cell invasion. Nearly all human PDAC samples expressed fascin, and
      higher fascin histoscores correlated with poor outcomes, vascular invasion, and
      time to recurrence. CONCLUSIONS: The actin-bundling protein fascin is regulated
      by slug and involved in late-stage PanIN and PDAC formation in mice. Fascin
      appears to promote formation of filopodia and invasive activities of PDAC cells.
      Its levels in human PDAC correlate with outcomes and time to recurrence,
      indicating it might be a marker or therapeutic target for pancreatic cancer.

PMID- 24462736
TI  - How are cerebral performance category scores measured for audit and research
      purposes?

PMID- 24462735
TI  - Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive
      patients with normal levels of alanine aminotransferase and high levels of
      hepatitis B virus DNA.
AB  - BACKGROUND & AIMS: Little is known about the benefit of antiviral therapy for
      hepatitis B e antigen (HBeAg)-positive patients with high viral load and normal
      levels of alanine aminotransferase. We evaluated the effects of single and
      combination therapies in immune-tolerant patients with chronic hepatitis B.
      METHODS: In a double-blind study, nucleos(t)ide-naive patients with high levels
      of hepatitis B virus (HBV) DNA who were positive for HBeAg and had normal levels
      of alanine aminotransferase were randomly assigned to groups given either oral
      tenofovir disoproxil fumarate (TDF, 300 mg) and placebo (n = 64) or a combination
      of TDF (300 mg) and emtricitabine (200 mg, n = 62) for 192 weeks. The primary end
      point was proportion of patients with serum levels of HBV DNA <69 IU/mL at week
      192. RESULTS: The study population (mean age was 33 years; 89% were Asian) was
      predominantly infected with HBV genotypes B and C (93%), 99% were HBeAg positive
      with a mean baseline level of HBV DNA of 8.41 log10 IU/mL. At week 192, 55% of
      patients (35 of 64) in the TDF+placebo group and 76% of patients (47 of 62) in
      the TDF+emtricitabine group had levels of HBV DNA <69 IU/mL (P = .016). No
      patients were found to have viral resistance to therapy. HBeAg seroconversion
      occurred in 3 patients (5%), all in the TDF+placebo group; no patient had loss of
      hepatitis B surface antigen. In multivariate analysis, female sex (odds ratio =
      7.05; P = .002) and TDF+emtricitabine treatment (odds ratio = 3.9; P = .01) were
      associated with a favorable response. Both regimens were well tolerated.
      CONCLUSIONS: In HBeAg-positive patients with chronic HBV infection, high viral
      loads, normal levels of alanine aminotransferase, and therapy with the
      combination of TDF and emtricitabine provided better viral suppression than TDF
      alone, although rates of HBeAg seroconversion and hepatitis B surface antigen
      loss were low.

PMID- 24462737
TI  - Complementary and alternative approaches used by parents of children with
      epilepsy on epilepsy management.
AB  - The aim of this study was to determine the complementary and alternative
      approaches used by parents of children with epilepsy on epilepsy management. This
      descriptive study included a total of 304 parents of children with epilepsy aged
      between 0 and 18years evaluated at the Pediatric Neurology Clinic of Akdeniz
      University Hospital in Turkey between January and May 2013. Data were collected
      by using a questionnaire developed by the researchers. It was determined that all
      the parents use complementary and alternative approaches for their children with
      epilepsy, and the most common approaches are praying (99.3%); keeping their
      children away from the effects of smoking (79.8%); feeding their children walnuts
      (79.6%), butter (59.2%), and bone marrow (58.6%); providing their children with
      good quality sleep (58.6%); and enabling their children to play games (51%). The
      approaches commonly applied during seizures include praying (96.2%), comforting
      their children in their arms and showing affection (55.6%), waiting for seizures
      to finish at home (45.7%), and laying children on their side (41.1%). Of parents,
      98% stated that alternative approaches enable them to control their child's
      seizures, 100% said that alternative approaches have no adverse effect, and 98.4%
      stated that they will continue to use these approaches. The children's approaches
      to cope with epilepsy included looking after pets (72.7%), listening to music
      (70.1%), watching television (64.5%), playing games (55.3%), praying (51%), and
      spending time with friends (48.7%). Most of the approaches used by parents and
      children with epilepsy for the management of illness are determined to consist of
      complementary approaches that may contribute to management of epilepsy. Knowing
      the approaches of parents and children with epilepsy that could adversely affect
      disease management is important for educating parents and children to avoid these
      potentially harmful interventions. 

PMID- 24462738
TI  - Role of microRNA-27a in down-regulation of angiogenic factor AGGF1 under hypoxia
      associated with high-grade bladder urothelial carcinoma.
AB  - Hypoxia stimulates angiogenesis under a variety of pathological conditions,
      including malignant tumors by inducing expression of angiogenic factors such as
      VEGFA. Surprisingly, here we report significant association between down
      regulation of a new angiogenic factor AGGF1 and high-grade urothelial carcinoma.
      The proportion of strong AGGF1 expression cases was significantly lower in the
      high-grade urothelial carcinoma group than that in the low-grade urothelial
      carcinoma group (P=1.40*10(-5)) or than that in the normal urothelium tissue
      group (P=2.11*10(-4)). We hypothesized that tumor hypoxia was responsible for
      differential expression of the AGGF1 protein in low- and high-grade urothelial
      carcinomas, and therefore investigated the molecular regulatory mechanism for
      AGGF1 expression under hypoxia. Under hypoxic conditions, AGGF1 protein levels
      declined without any change in mRNA levels and protein stability. Hypoxia-induced
      down-regulation of AGGF1 was mediated by miR-27a. Overexpression of miR-27a
      suppressed AGGF1 expression through translational inhibition, but not by RNA
      degradation. Moreover, the hypoxia-induced decrease of AGGF1 expression
      disappeared after miR-27a expression was inhibited. Furthermore, down-regulation
      of AGGF1 reduced hypoxia-induced apoptosis in cancer cells. Taken together, the
      results of this study indicate that (1) hypoxia down-regulates expression of the
      AGGF1 protein, but not AGGF1 mRNA, by inducing expression of miR-27a; (2) Down
      regulation of AGGF1 had an apparent protective role for cancer cells under
      hypoxia; (3) Down-regulation of the AGGF1 protein confers a significant risk of
      high-grade human urothelial bladder carcinoma.

PMID- 24462740
TI  - Free TRAM breast reconstruction and ipsilateral interval pedicled TRAM
      reconstruction for second breast in one patient.
AB  - Autologous breast reconstruction can give excellent cosmetic results and is
      preferred by some women. Donor tissue can be scarce however, especially for
      bilateral reconstructions and/or when a large breast is needed. In addition, the
      decision of which donor tissue to use in unilateral reconstruction may have an
      impact on a subsequent reconstruction if needed. We present a case of a patient
      who required a large volume unilateral reconstruction, performed using a free
      TRAM flap, who then re-presented 10 years later with disease in the contralateral
      breast. For her second reconstruction, a pedicled TRAM was used from the same
      side as the previous free TRAM. We believe that this sequence of reconstructions
      using the TRAM twice on the same side has not been previously reported. 

PMID- 24462741
TI  - Salvage of ulcerating metastatic inguinal lymphadenopathy using the inferior
      pedicled TRAM flap.

PMID- 24462739
TI  - Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in
      hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid.
AB  - Hypercholesterolemia and polymorphisms in the cholesterol exporter ABCA1 are
      linked to age-related macular degeneration (AMD). Excessive iron in retina also
      has a link to AMD pathogenesis. Whether these findings mean a
      biological/molecular connection between iron and cholesterol is not known. Here
      we examined the relationship between retinal iron and cholesterol using a mouse
      model (Hfe(-/-)) of hemochromatosis, a genetic disorder of iron overload. We
      compared the expression of the cholesterol efflux transporters ABCA1 and ABCG1
      and cholesterol content in wild type and Hfe(-/-) mouse retinas. We also
      investigated the expression of Bdh2, the rate-limiting enzyme in the synthesis of
      the endogenous siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA) in wild type and
      Hfe(-/-) mouse retinas, and the influence of this siderophore on ABCA1/ABCG1
      expression in retinal pigment epithelium. We found that ABCA1 and ABCG1 were
      expressed in all retinal cell types, and that their expression was decreased in
      Hfe(-/-) retina. This was accompanied with an increase in retinal cholesterol
      content. Bdh2 was also expressed in all retinal cell types, and its expression
      was decreased in hemochromatosis. In ARPE-19 cells, 2,5-DHBA increased
      ABCA1/ABCG1 expression and decreased cholesterol content. This was not due to
      depletion of free iron because 2,5-DHBA (a siderophore) and deferiprone (an iron
      chelator) had opposite effects on transferrin receptor expression and ferritin
      levels. We conclude that iron is a regulator of cholesterol homeostasis in retina
      and that removal of cholesterol from retinal cells is impaired in
      hemochromatosis. Since excessive cholesterol is pro-inflammatory, hemochromatosis
      might promote retinal inflammation via cholesterol in AMD.

PMID- 24462742
TI  - Conditioning chemotherapy dose adjustment in obese patients: a review and
      position statement by the American Society for Blood and Marrow Transplantation
      practice guideline committee.
AB  - Hematopoietic stem cell transplantation (HCT) is a potentially life-saving
      therapy for patients with malignant and nonmalignant disease states. This article
      reviews the current published literature on the dosing of pharmacologic agents
      used for HCT preparative regimens with specific focus on the obese patient
      population. The review found that dose adjustments for obesity have, to date,
      been based empirically or extrapolated from published data in the
      nontransplantation patient population. As a result, the Committee determined that
      clear standards or dosing guidelines are unable to be made for the obese
      population because Level I and II evidence are unavailable at this time. Instead,
      the Committee provides a current published literature review to serve as a
      platform for conditioning agent dose selection in the setting of obesity. A
      necessary goal should be to encourage future prospective trials in this patient
      population because further information is needed to enhance our knowledge of the
      pharmacokinetics and pharmacodynamics of conditioning agents in the setting of
      obesity. 

PMID- 24462743
TI  - Post-transplantation B cell activating factor and B cell recovery before onset of
      chronic graft-versus-host disease.
AB  - Excessive levels of B cell activating factor (BAFF) are found in patients with
      active chronic graft-versus-host disease (cGVHD). In mice, BAFF has been shown to
      be essential for B cell recovery after myeloablation. To assess how BAFF levels
      relate to transplantation factors and subsequent development of cGVHD, we
      prospectively monitored 412 patients in the first year after allogeneic
      peripheral blood or bone marrow hematopoietic stem cell transplantation (HSCT)
      and censored data at time of cGVHD onset. In patients who did not develop cGVHD,
      we affirmed a temporal pattern of gradually decreasing BAFF levels as B cell
      numbers increase after myeloablative conditioning. In contrast, after reduced
      intensity conditioning, BAFF levels remained high throughout the first post-HSCT
      year, suggesting that the degree of myeloablation resulted in delayed B cell
      recovery associated with persistence of higher BAFF levels. Given that high
      BAFF/B cell ratios have been associated with active cGVHD, we examined
      differences in early BAFF/B cell ratios and found significantly different BAFF/B
      cell ratios at 3 months post-HSCT only after myeloablative conditioning in
      patients who subsequently developed cGVHD. In addition to HSCT conditioning type,
      the use of sirolimus was significantly associated with higher BAFF levels after
      HSCT, and this also was potentially related to lower B cell numbers. Taken
      together, our results are important for interpreting BAFF measurements in cGVHD
      biomarker studies. 

PMID- 24462744
TI  - Gene and miRNA expression profiles of hematopoietic progenitor cells vary
      depending on their origin.
AB  - Hematopoietic progenitor cells (HPCs) from granulocyte colony-stimulating factor
      (G-CSF)-mobilized peripheral blood (G-PB), bone marrow (BM), or umbilical cord
      blood (CB) have differing biological properties and differing kinetics of
      engraftment post-transplantation, which might be explained, at least in part, by
      differing gene and miRNA expression patterns. To assess the differences in gene
      and miRNA expression, we analyzed whole genome expression profiles as well as the
      expression of 384 miRNAs in CD34(+) cells isolated from 18 healthy individuals (6
      individuals per subtype of HPC source). We identified 43 genes and 36 miRNAs
      differentially expressed in the various CD34(+) cell sources. We observed that
      CD34(+) cells from CB and BM showed similar gene and miRNA expression profiles,
      whereas CD34(+) cells from G-PB had a very different expression pattern.
      Remarkably, 20 of the differentially expressed genes are targets of the
      differentially expressed miRNAs. Of note, the majority of genes differentially
      expressed in CD34(+) cells from G-PB are involved in cell cycle regulation,
      promoting the process of proliferation, survival, hematopoiesis, and cell
      signaling, and are targets of overexpressed and underexpressed miRNAs in CD34(+)
      cells from the same source. These data suggest significant differences in gene
      and miRNA expression among the various HPC sources used in transplantation. We
      hypothesize that the differentially expressed genes and miRNAs involved in cell
      cycle and proliferation might explain the differing kinetics of engraftment
      observed after transplantation of hematopoietic stem cells obtained from these
      different sources. 

PMID- 24462745
TI  - Crystal structure of NTPDase2 in complex with the sulfoanthraquinone inhibitor
      PSB-071.
AB  - In many vertebrate tissues CD39-like ecto-nucleoside triphosphate
      diphosphohydrolases (NTPDases) act in concert with ecto-5'-nucleotidase (e5NT,
      CD73) to convert extracellular ATP to adenosine. Extracellular ATP is a
      cytotoxic, pro-inflammatory signalling molecule whereas its product adenosine
      constitutes a universal and potent immune suppressor. Interference with these
      ectonucleotidases by use of small molecule inhibitors or inhibitory antibodies
      appears to be an effective strategy to enhance anti-tumour immunity and suppress
      neoangiogenesis. Here we present the first crystal structures of an NTPDase
      catalytic ectodomain in complex with the Reactive Blue 2 (RB2)-derived inhibitor
      PSB-071. In both of the two crystal forms presented the inhibitor binds as a
      sandwich of two molecules at the nucleoside binding site. One of the molecules is
      well defined in its orientation. Specific hydrogen bonds are formed between the
      sulfonyl group and the nucleoside binding loop. The methylphenyl side chain
      functionality that improved NTPDase2-specificity is sandwiched between R245 and
      R394, the latter of which is exclusively found in NTPDase2. The second molecule
      exhibits great in-plane rotational freedom and could not be modelled in a
      specific orientation. In addition to this structural insight into NTPDase
      inhibition, the observation of the putative membrane interaction loop (MIL) in
      two different conformations related by a 10 degrees  rotation identifies the MIL
      as a dynamic section of NTPDases that is potentially involved in regulation of
      catalysis. 

PMID- 24462746
TI  - Recombination analysis based on the HAstV-2 and HAstV-4 complete genomes.
AB  - Complete genome sequences of previously unstudied human astrovirus subgenotypes -
      HAstV-2a and HAstV-2c - and two isolates of a rare genotype HAstV-4 have been
      determined. These isolates were recovered from fecal samples of young children
      hospitalized with acute intestinal infections in Novosibirsk (Russia). Three of
      the four sequenced isolates (HAstV-2a, HAstV-2c, and HAstV-4) are recombinants.
      It has been shown that all known HAstV-2 genomes have emerged via recombination;
      the HAstV-1 and HAstV-4 genotypes contain both recombinant and non-recombinant
      isolates; and all HAstV-3, HAstV-5, and HAstV-6 whole-genome sequences display no
      reliable signs of recombination. The average mutation accumulation rate has been
      determined based on an extended ORF2 fragment and amounts to 1.0*10(-3)
      substitutions per site per year. The evolutionary chronology of current HAstV
      genotypes has been reconstructed. 

PMID- 24462747
TI  - Editor's perspectives - February 2014.

PMID- 24462748
TI  - Depth perception of illusory surfaces.
AB  - The perception of an illusory surface, a subjectively perceived surface that is
      not given in the image, is one of the most intriguing phenomena in vision. It
      strongly influences the perception of some fundamental properties, namely, depth,
      lightness and contours. Recently, we suggested (1) that the context-sensitive
      mechanism of depth computation plays a key role in creating the illusion, (2)
      that the illusory lightness perception can be explained by an influence of depth
      perception on the lightness computation, and (3) that the perception of
      variations of the Kanizsa figure can be well-reproduced by implementing these
      principles in a model (Kogo, Strecha, et al., 2010). However, depth perception,
      lightness perception, contour perception, and their interactions can be
      influenced by various factors. It is essential to measure the differences between
      the variation figures in these aspects separately to further understand the
      mechanisms. As a first step, we report here the results of a new experimental
      paradigm to compare the depth perception of the Kanizsa figure and its
      variations. One of the illusory figures was presented side-by-side with a non
      illusory variation whose stereo disparities were varied. Participants had to
      decide in which of these two figures the central region appeared closer. The
      results indicate that the depth perception of the illusory surface was indeed
      different in the variation figures. Furthermore, there was a non-linear
      interaction between the occlusion cues and stereo disparity cues. Implications of
      the results for the neuro-computational mechanisms are discussed. 

PMID- 24462749
TI  - Posttraumatic stress disorder and alcohol dependence: individual and combined
      associations with social network problems.
AB  - People with either posttraumatic stress disorder (PTSD) or alcohol dependence
      (AD) are apt to report problems in their social networks, including low perceived
      support and elevated conflict. However, little research has examined social
      networks among people with comorbid PTSD/AD despite evidence suggesting these two
      conditions commonly co-occur and are linked to particularly severe problems. To
      test the hypothesis that people with comorbid PTSD/AD experience particularly
      elevated social network problems, individuals with lifetime diagnoses of PTSD,
      AD, comorbid PTSD/AD, or no lifetime history of Axis I psychopathology in the
      National Comorbidity Survey-Replication were compared on four dimensions of
      social networks: (1) Closeness, (2) Conflict, (3) Family Support, and (4)
      Apprehension. Persons with PTSD, AD, or comorbid PTSD/AD endorsed more problems
      with the Conflict, Family Support, and Apprehension factors compared to people
      with no history of Axis I psychopathology. Moreover, individuals with comorbid
      PTSD/AD endorsed greater Apprehension and significantly less Family Support
      compared to the other three groups. Results suggest people with comorbid PTSD/AD
      experience increased problems with their family as well as greater concerns about
      enlisting social support than even people with PTSD or AD alone. Treatments for
      people suffering from comorbid PTSD/AD should consider assessing for and possibly
      targeting family support and apprehension about being close to others. 

PMID- 24462750
TI  - Benznidazole-resistance in Trypanosoma cruzi: evidence that distinct mechanisms
      can act in concert.
AB  - Benznidazole is the main drug used to treat Trypanosoma cruzi infections.
      However, frequent instances of treatment failure have been reported. To better
      understand potential resistance mechanisms, we analysed three clones isolated
      from a single parasite population that had undergone benznidazole-selection.
      These clones exhibited differing levels of benznidazole-resistance (varying
      between 9 and 26-fold), and displayed cross-resistance to nifurtimox (2 to 4
      fold). Each clone had acquired a stop-codon-generating mutation in the gene which
      encodes the nitroreductase (TcNTR) that is responsible for activating
      nitroheterocyclic pro-drugs. In addition, one clone had lost a copy of the
      chromosome containing TcNTR. However, these processes alone are insufficient to
      account for the extent and diversity of benznidazole-resistance. It is implicit
      from our results that additional mechanisms must also operate and that T. cruzi
      has an intrinsic ability to develop drug-resistance by independent sequential
      steps, even within a single population. This has important implications for drug
      development strategies. 

PMID- 24462751
TI  - The Spatial Orienting paradigm: how to design and interpret spatial attention
      experiments.
AB  - This paper is conceived as a guide that will describe the very well known Spatial
      Orienting paradigm, used to explore attentional processes in healthy individuals
      as well as in people suffering from psychiatric disorders and brain-damaged
      patients. The paradigm was developed in the late 1970s, and since then, it has
      been used in thousands of attentional studies. In this review, we attempt to
      describe, the paradigm for the naif reader, and explain in detail when is it
      used, which variables are usually manipulated, how to interpret its results, and
      how can it be adapted to different populations and methodologies. The main goal
      of this review is to provide a practical guide to researchers who have never used
      the paradigm that will help them design their experiments, as a function of their
      theoretical and experimental needs. We also focus on how to adapt the paradigm to
      different technologies (such as event-related potentials, functional resonance
      imaging, or transcranial magnetic stimulation), and to different populations by
      presenting an example of its use in brain-damaged patients. 

PMID- 24462753
TI  - Molecular characterization, transcriptional regulation and association analysis
      with carcass traits of porcine TCAP gene.
AB  - TCAP (also known as titin-cap or telethonin) is one of the titin interacting Z
      disk proteins involved in the regulation and development of normal sarcomeric
      structure. In this study, we cloned the cDNA and promoter sequences of porcine
      TCAP gene, which contained a 504 bp full-length coding region. Quantitative real
      time PCR (qRT-PCR) analyses showed that porcine TCAP was highly expressed in the
      skeletal muscle, heart, and kidney. During postnatal muscle development, TCAP
      expression was down-regulated from 30 days to 120 days in Large White and Meishan
      pigs. One single nucleotide polymorphism c.334 G>A in exon 2 of the TCAP gene was
      identified and detected by allele-specific primer-polymerase chain reaction (ASP
      PCR). Association analysis revealed that the polymorphism had significant
      associations (P<0.05 and P<0.01) with some carcass traits. Analysis of the
      porcine TCAP promoter in different cell lines demonstrated that it is a muscle
      specific promoter. In addition, we found that the porcine TCAP promoter can be
      activated by MyoD, MyoG and MEF2 in myotubes, which indicated that TCAP may play
      a role in the regulation of porcine skeletal muscle development. These findings
      provide useful information for the further investigation of the function of TCAP
      in porcine skeletal muscle.

PMID- 24462752
TI  - The form and function of hippocampal context representations.
AB  - Context is an essential component of learning and memory processes, and the
      hippocampus is critical for encoding contextual information. However, connecting
      hippocampal physiology with its role in context and memory has only recently
      become possible. It is now clear that contexts are represented by coherent
      ensembles of hippocampal neurons and new optogenetic stimulation studies indicate
      that activity in these ensembles can trigger the retrieval of context appropriate
      memories. We interpret these findings in the light of recent evidence that the
      hippocampus is critically involved in using contextual information to prevent
      interference, and propose a theoretical framework for understanding contextual
      influence on memory retrieval. When a new context is encountered, a unique
      hippocampal ensemble is recruited to represent it. Memories for events that occur
      in the context become associated with the hippocampal representation. Revisiting
      the context causes the hippocampal context code to be re-expressed and the
      relevant memories are primed. As a result, retrieval of appropriate memories is
      enhanced and interference from memories belonging to other contexts is minimized.

PMID- 24462754
TI  - Genome-wide identification of members in the YTH domain-containing RNA-binding
      protein family in apple and expression analysis of their responsiveness to
      senescence and abiotic stresses.
AB  - YT521-homology (YTH) domain-containing RNA-binding proteins (YTPs) are a small
      gene family involved in post-transcriptional regulation. We identified 26
      putative YTP gene models in the apple genome. Although plant YTPs have been
      classified into three groups, those in multi-cellular organisms belong only to
      Groups A and B. The apple genome contains 22 YTP gene models in Group A and four
      in Group B. Duplication analysis showed that tandem and segmental duplications
      contributed only partially to an expansion in apple YTP numbers. YTH was the only
      recognizable domain in apple YTPs; its three-dimensional structure implied
      possible motifs for RNA-binding. After the assembly of expressed sequence tags
      (ESTs) and gene-cloning, we were able to identify 14 apple YTPs that were
      expressed in various tissues, especially senescing leaves. Expression analysis
      showed that these YTPs also responded to several abiotic stresses. Taken
      together, our genome-wide evaluation provides new insight for further research on
      the effects of those stresses.

PMID- 24462755
TI  - Molecular characterization and expression patterns of the actinin-associated LIM
      protein (ALP) subfamily genes in porcine skeletal muscle.
AB  - The actinin-associated LIM protein (ALP) subfamily has important functions in
      cell signal transduction, cell proliferation, and integration of cytoskeletal
      architecture. To detect their functions in pig skeletal muscle, we cloned and
      characterized the pig ALP subfamily genes, drew their genomic structure maps, and
      detected their tissue expression patterns. We identified a new spliced variant of
      PDLIM3 in pig skeletal muscle and named it as PDLIM3-4, which was only expressed
      in the heart and skeletal muscle. Our results showed that PDLIM3-4 was expressed
      in adult pig skeletal muscle with the highest expression level, and both PDLIM3-4
      isoform and PDLIM4 had different expression profiles during the prenatal and
      postnatal stages of skeletal muscle development among the three pig breeds. These
      studies provide useful information for further research on the functions of pig
      ALP subfamily genes in skeletal muscle development. 

PMID- 24462756
TI  - The sigma(F)-specific anti-sigma factor RsfA is one of the protein kinases that
      phosphorylates the pleiotropic anti-anti-sigma factor BldG in Streptomyces
      coelicolor A3(2).
AB  - The anti-anti-sigma factor BldG has a role in the morphological differentiation
      and antibiotic production of Streptomyces coelicolor A3(2). Together with the
      anti-sigma factor UshX it is involved in the "partner-switching"-like activation
      of the sigma factor sigma(H) that has a dual role in the osmotic stress response
      and morphological differentiation in S. coelicolor A3(2). Although BldG is
      phosphorylated in vivo in S. coelicolor, neither of the interacting anti-sigma
      factors UshX and ApgA is found to phosphorylate it. By using a combination of
      several approaches, we demonstrated a direct interaction between BldG and the
      anti-sigma factor RsfA, which has been previously shown to regulate antibiotic
      production and morphological differentiation in S. coelicolor and to specifically
      interact with the sporulation-specific sigma factor sigma(F). RsfA phosphorylates
      BldG in vitro, demonstrating that RsfA is a specific kinase for BldG and
      negatively regulates its activity. However, another interacting anti-anti-sigma
      factor homolog, SCO0869, was not phosphorylated by RsfA. Transcriptional analyses
      of rsfA revealed a single promoter, the activity of which was repressed by
      osmotic stress and decreased during differentiation. These data suggested that
      BldG has a pleiotropic role in the regulation of at least two sigma factors,
      sigma(H) and sigma(F), in S. coelicolor. 

PMID- 24462757
TI  - Novel polymorphisms of SIX4 gene and their association with body measurement
      traits in Qinchuan cattle.
AB  - Sine oculis homeobox homolog 4 (SIX4) gene belongs to the sine oculis/SIX gene
      family, which includes six members in vertebrates. SIX4 gene plays a crucial role
      in skeletal myogenesis, and its genetic variations or deficiency may cause
      hypopituitarism, suggesting that SIX4 gene is a potential candidate gene
      affecting body measurement traits (BMTs) in animals. Herein, the objectives of
      this study were to identify genetic polymorphisms of bovine SIX4 gene and to
      analyze potential association between single nucleotide polymorphisms (SNPs) and
      body measurement traits in Qinchuan cattle. In the present study, we investigated
      polymorphisms of SIX4 gene in 426 Qinchuan cattle using DNA sequencing and
      polymerase chain reaction-restriction fragment length polymorphisms. Three novel
      SNPs were identified within bovine SIX4 gene. Associations between body
      measurement traits and SIX4 gene polymorphisms were investigated, and significant
      statistical associations were found between polymorphisms of these three SNPs and
      body measurement traits (P<0.05). Hence, based on results obtained from this
      study, we conjectured that SIX4 gene may have potential effects on body
      measurement traits in Qinchuan cattle population and could be used for marker
      assisted selection. 

PMID- 24462758
TI  - WFS1 and non-syndromic low-frequency sensorineural hearing loss: a novel mutation
      in a Portuguese case.
AB  - Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in
      which frequencies at 2,000 Hz and below are predominantly affected. Most of the
      families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin.
      A Portuguese patient aged 49, reporting HL since her third decade of life, and
      also referring tinnitus, was shown to display bilateral moderate LFSNHL after
      audiological evaluation. Molecular analysis led to the identification of a novel
      mutation, c.511G>A (p.Asp171Asn), found in heterozygosity in the exon 5 of the
      WFS1 gene, and changing the aspartic acid at position 171 to an asparagine, in
      the extracellular N-terminus domain of the wolframin protein. This novel mutation
      wasn't present either in 200 control chromosomes analyzed or in the hearing
      proband's half-brother, and it had not been reported in 1000 Genomes, Exome
      Variant Server, HGMD or dbSNP databases. No mutations were found in GJB2 and GJB6
      genes. Multi-alignment of 27 wolframin sequences from mammalian species, against
      the human wolframin sequence in ConSurf, indicated a conservation score
      corresponding to 7 in a 1-9 color scale where 9 is conserved and 1 is variable.
      In addition, the mutation p.Asp171Asn was predicted to be damaging and possibly
      damaging by SIFT and Polyphen-2, respectively. The auditory phenotype of this
      patient could thus be due to the novel mutation p.Asp171Asn. Further functional
      characterization might enable to elucidate in which way the change in the residue
      171, as other changes introduced by LFSNHL-associated mutations previously
      described, leads to this type of HL.

PMID- 24462759
TI  - Targeting therapeutic hypothermia in neonatal resuscitation and beyond: it is
      time to phenotype.

PMID- 24462760
TI  - Chest wall abnormalities and their clinical significance in childhood.
AB  - The thorax consists of the rib cage and the respiratory muscles. It houses and
      protects the various intrathoracic organs such as the lungs, heart, vessels,
      esophagus, nerves etc. It also serves as the so-called "respiratory pump" that
      generates the movement of air into the lungs while it prevents their total
      collapse during exhalation. In order to be performed these functions depend on
      the structural and functional integrity of the rib cage and of the respiratory
      muscles. Any condition (congenital or acquired) that may affect either one of
      these components is going to have serious implications on the function of the
      other. Furthermore, when these abnormalities occur early in life, they may affect
      the growth of the lungs themselves. The following article reviews the physiology
      of the respiratory pump, provides a comprehensive list of conditions that affect
      the thorax and describes their effect(s) on lung growth and function. 

PMID- 24462761
TI  - Assessment of the translational value of mouse lupus models using clinically
      relevant biomarkers.
AB  - Lupus is an autoimmune disease with a poorly understood etiology that manifests
      with a diverse pathology. This heterogeneity has been a challenge to clinical
      drug development efforts. A related difficulty is the uncertain translational
      power of animal models used for evaluating potential drug targets and candidate
      therapeutics, because it is unlikely that any 1 preclinical model will
      recapitulate the spectrum of human disease. Therefore, multiple models, along
      with an understanding of the immune mechanisms that drive them, are necessary if
      we are to use them to identify valid drug targets and evaluate candidate
      therapies successfully. To this end, we have characterized several different
      mouse lupus models and report their differences with respect to biomarkers and
      symptoms that are representative of the human disease. We compared the pristane
      induced mouse lupus disease model using 3 different strains (DBA/1, SJL, BALB/c),
      and the spontaneous NZB x NZW F1(NZB/W) mouse model. We show that the models
      differ significantly in their autoantibody profiles, disease manifestations such
      as nephritis and arthritis, and expression of type I interferon-regulated genes.
      Similar to the NZB/W model, pristane-induced disease in SJL mice manifests with
      nephritis and proteinuria, whereas the pristane-treated DBA/1 mice develop
      arthritis and an interferon-driven gene signature that closely resembles that in
      human patients. The elucidation of each model's strengths and the identification
      of translatable biomarkers yields insight for basic lupus research and drug
      development, and should assist in the proper selection of models for evaluating
      candidate targets and therapeutic strategies.

PMID- 24462762
TI  - Prognostic advantage of irinotecan dose escalation according to uridine
      diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping in patients with
      metastatic colorectal cancer treated with bevacizumab combined with 5
      fluorouracil/leucovorin with irinotecan in a first-line setting.
AB  - This study compared the clinical responses of patients with metastatic colorectal
      cancer (mCRC) with 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) plus
      bevacizumab therapy either with or without uridine diphosphate
      glucuronosyltransferase 1A1 (UGT1A1) genotyping and irinotecan dose escalation.
      Of 107 total patients with mCRC, 79 were classified as the study group and 28 as
      the control group. The study group received irinotecan dose escalation based on
      UGT1A1 genotyping whereas the control group did not. Clinicopathologic features,
      response rates, and survival were compared for the 2 groups. The clinical
      response rate of patients with mCRC treated with FOLFIRI plus bevacizumab under
      UGT1A1 genotyping and irinotecan dose escalation was significantly better than
      that of those without these prospective tests and dose escalation (P = 0.028).
      Both progression-free survival (PFS) and overall survival were significantly
      greater in clinical responders than nonresponders (both, P < 0.001), and PFS was
      significantly greater among the study group patients than among the control group
      patients, with a median PFS of 12.2 months vs 9.4 months (P = 0.025). Grade 3/4
      adverse events were not significantly different between the 2 groups (P = 0.189).
      Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of
      irinotecan to obtain a better clinical response/outcome with comparable
      toxicities.

PMID- 24462763
TI  - Migraine headache confounding the diagnosis of acute mountain sickness.
AB  - A 36-year-old man with a history of migraine headache attempted to hike from
      Lukla, Nepal, to Mount Everest Base Camp. On the sixth day of hiking, he had a
      migraine headache. After achieving resolution with typical therapies and rest, he
      ascended higher. Another headache developed that was interpreted to be a
      migraine. The headache was treated, and he ascended higher, after which severe
      symptoms of acute mountain sickness developed, necessitating his evacuation by
      helicopter. Persons with headaches in daily life may present challenges to
      diagnosis when traveling to high altitude. Careful evaluation and decision making
      are needed to achieve proper diagnosis and treatment of acute mountain sickness. 

PMID- 24462764
TI  - Evidence for baseline glucocorticoids as mediators of reproductive investment in
      a wild bird.
AB  - Determining the mechanisms that mediate investment decisions between current and
      future reproductive attempts is still a key goal of life-history studies. Since
      baseline levels of stress hormones (glucocorticoids - GCs) act as predictive and
      labile regulators of daily energetic balance in vertebrates they remain excellent
      candidates for mediating investment decisions both within and across reproductive
      attempts. Using free-living female European starlings (Sturnus vulgaris) we
      experimentally reduced investment in current reproduction (number of offspring
      raised in the first brood) to examine whether baseline corticosterone (CORT)
      acted as a hormonal mediator preparing individuals for a predictable increase in
      future investment (number of offspring raised in the second brood). Although
      treatment and control birds raised the same total amount of offspring across two
      broods, the experimental birds increased reproductive investment in second broods
      to compensate for the reduced investment in the first brood. Data on both mean
      and intra-individual changes in baseline CORT support the idea that an increase
      in baseline CORT between the incubation stages in treatment birds strongly
      predicted this increase in investment. Importantly, we measured the increase in
      baseline CORT during late incubation prior to the increase in energetic demand
      associated with increased reproductive investment in offspring, indicating that
      flexible within-individual changes in baseline GCs can act as a labile mechanism
      preparing individuals for predictable increases in reproductive investment. As
      such, our experimental results indicate that elevated baseline GCs can prepare
      individuals for investment in energetically expensive life-history stages, rather
      than simply being elevated as a consequence of increased effort or demand. This
      suggests that short-term preparative increases in baseline GCs benefit
      individuals by successfully allowing them to maximize fitness under varying
      environmental conditions. 

PMID- 24462765
TI  - Advances in artificial joint materials.

PMID- 24462766
TI  - Prediction of methotrexate CNS distribution in different species - influence of
      disease conditions.
AB  - Children and adults with malignant diseases have a high risk of prevalence of the
      tumor in the central nervous system (CNS). As prophylaxis treatment methotrexate
      is often given. In order to monitor methotrexate exposure in the CNS,
      cerebrospinal fluid (CSF) concentrations are often measured. However, the
      question is in how far we can rely on CSF concentrations of methotrexate as
      appropriate surrogate for brain target site concentrations, especially under
      disease conditions. In this study, we have investigated the spatial distribution
      of unbound methotrexate in healthy rat brain by parallel microdialysis, with or
      without inhibition of Mrp/Oat/Oatp-mediated active transport processes by a co
      administration of probenecid. Specifically, we have focused on the relationship
      between brain extracellular fluid (brainECF) and CSF concentrations. The data
      were used to develop a systems-based pharmacokinetic (SBPK) brain distribution
      model for methotrexate. This model was subsequently applied on literature data on
      methotrexate brain distribution in other healthy and diseased rats (brainECF),
      healthy dogs (CSF) and diseased children (CSF) and adults (brainECF and CSF).
      Important differences between brainECF and CSF kinetics were found, but we have
      found that inhibition of Mrp/Oat/Oatp-mediated active transport processes does
      not significantly influence the relationship between brainECF and CSF fluid
      methotrexate concentrations. It is concluded that in parallel obtained data on
      unbound brainECF, CSF and plasma concentrations, under dynamic conditions,
      combined with advanced mathematical modeling is a most valid approach to develop
      SBPK models that allow for revealing the mechanisms underlying the relationship
      between brainECF and CSF concentrations in health and disease. 

PMID- 24462767
TI  - Correlation of 3-mercaptopropionic acid induced seizures and changes in striatal
      neurotransmitters monitored by microdialysis.
AB  - OBJECTIVES: The goal of this study was to use a status epilepticus steady-state
      chemical model in rats using the convulsant, 3-mercaptopropionic acid (3-MPA),
      and to compare the changes in striatal neurotransmission on a slow (5min) and
      fast (60s) timescale. In vivo microdialysis was combined with
      electrophysiological methods in order to provide a complete evaluation of the
      dynamics of the results obtained. OBJECTIVE: To compare the effects of a steady
      state chemical model pof status epilepticus on striatal amino-acid and amine
      neurotransmitters contents, as measured via in vivo microdialysis combined with
      electrophysiological methods. Measurements were performed on samples collected
      every 60s and every 5min. "Fast" (60s) and "slow" (5min) sampling timescales were
      selected, to gain more insight into the dynamics of GABA synthesis inhibition and
      of its effects on other neurotransmitters and on cortical electrical activity.
      METHODS: 3-MPA was administered in the form of an intra-venous load (60mg/kg)
      followed by a constant infusion (50mg/kg/min) for min. Microdialysis samples were
      collected from the striatum at intervals of 5min and 60s and analyzed for
      biogenic amine and amino acid neurotransmitters. ECoG activity was monitored via
      screws placed over the cortex. RESULTS: In the 5min samples, glutamate (Glu)
      increased and gamma-aminobutyric acid (GABA) decreased monotonically while
      changes in dopamine (DA) concentration were bimodal. In the sixty second samples,
      Glu changes were bimodal, a feature that was not apparent with the 5min samples.
      ECoG activity was indicative of status epilepticus. CONCLUSIONS: This study
      describes the combination of in vivo microdialysis with electrophysiology to
      monitor the effect of 3-MPA on neurotransmission in the brain. This led to a
      better understanding of the chemical changes in the striatum due to the applied 3
      MPA chemical model of status epilepticus.

PMID- 24462768
TI  - MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl
      CoA synthetase long-chain family member 1 (ACSL1) mRNA.
AB  - The abnormal lipid metabolism is considered as a hallmarker of tumorigenesis.
      Liver is the central organ for metabolic homeostasis. Hence, the development of
      hepatocellular carcinoma (HCC) always exhibits alterations of metabolism.
      MicroRNAs emerge as key post-transcriptional modulators of gene expression in
      physiologic and pathologic states. Here, we aim to explore the mechanism of
      abnormal lipid metabolism of hepatoma cells. Previously, our group reported that
      miR-205 as a tumor suppressor was down-regulated in HCC. Therefore, we supposed
      that miR-205 might be involved in the event. Interestingly, in this study we
      uncover that miR-205 deregulates lipid metabolism in HCC through targeting acyl
      CoA synthetase long-chain family member 1 (ACSL1) mRNA, which is an important and
      abundant lipid metabolism enzyme in liver. We identified that miR-205 was able to
      down-regulate ACSL1 via targeting its 3'UTR in the cells. Oil red O staining
      showed that miR-205 disordered the lipogenesis in hepatoma cells and anti-miR-205
      resulted in the accumulation of triglyceride in the cells depending on ACSL1.
      Moreover, we validated that the low levels of miR-205 were negatively related to
      high levels of ACSL1 in clinical HCC tissues. The expression levels of ACSL1 and
      its metabolite triglyceride levels were remarkably increased in hepatitis B virus
      X protein (HBx)-induced liver cancer tissues from the HBx transgenic mice model.
      Thus, we conclude that miR-205-targeted ACSL1 may contribute to the abnormal
      lipid metabolism of liver cancer. Our finding provides new insights into the
      dysregulation of lipid metabolism in HCC mediated by miR-205 targeting ACSL1
      mRNA. 

PMID- 24462769
TI  - Gbetagamma interacts with mTOR and promotes its activation.
AB  - Diverse G protein-coupled receptors depend on Gbetagamma heterodimers to promote
      cell polarization and survival via direct activation of PI3Kgamma and potentially
      other effectors. These events involve full activation of AKT via its
      phosphorylation at Ser473, suggesting that mTORC2, the kinase that phosphorylates
      AKT at Ser473, is activated downstream of Gbetagamma. Thus, we tested the
      hypothesis that Gbetagamma directly contributes to mTOR signaling. Here, we
      demonstrate that endogenous mTOR interacts with Gbetagamma. Cell stimulation with
      serum modulates Gbetagamma interaction with mTOR. The carboxyl terminal region of
      mTOR, expressed as a GST-fusion protein, including the serine/threonine kinase
      domain, binds Gbetagamma heterodimers containing different Gbeta subunits, except
      Gbeta4. Both, mTORC1 and mTORC2 complexes interact with Gbeta1gamma2 which
      promotes phosphorylation of their respective substrates, p70S6K and AKT. In
      addition, chronic treatment with rapamycin, a condition known to interfere with
      assembly of mTORC2, reduces the interaction between Gbetagamma and mTOR and the
      phosphorylation of AKT; whereas overexpression of Galphai interfered with the
      effect of Gbetagamma as promoter of p70S6K and AKT phosphorylation. Altogether,
      our results suggest that Gbetagamma positively regulates mTOR signaling via
      direct interactions and provide further support to emerging strategies based on
      the therapeutical potential of inhibiting different Gbetagamma signaling
      interfaces.

PMID- 24462770
TI  - The synthesis and analysis of S-nitorsylated paraoxonase 1.
AB  - Post-translational modification (PTM) of proteins plays a crucial role in health
      and disease by affecting numerous aspects of protein structure, function,
      stability and subcellular localization. Protein S-nitrosylation is one type of
      PTM that involves the covalent modification of cysteine sulfhydryl groups with
      nitric oxide (NO) and has a regulatory impact similar to phosphorylation. The
      enzyme paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL),
      and is responsible for many of HDL's antiatherogenic properties. The enzyme
      contains a free thiol group at Cys-284 which can also be modified covalently. As
      part of our effort to study the effect of PTMs on PON1 activities and properties
      and its implication for cardiovascular disease, we examined PON1's ability to
      undergo S-nitrosylation on its free Cys-284. Recombinant (re) PON1 was trans-S
      nitrosylated by several NO donors, glutathione-NO (GSNO) was found to be the most
      effective. The S-nitrosylated rePON1 was analyzed by Q-TOF LC/MS and by Saville
      Griess assay: the two analytical methods revealed closely similar results. rePON1
      was also nitrosylated by nitrosylated human serum albumin (HSA-NO) via protein
      protein trans-nitrosylation. HSA-NO transferred an NO group to rePON1 much more
      efficiently than GSNO with the formation of a higher than 70% rePON-NO when
      incubated with a 40-fold excess of a HSA-NO/HSA mixture. RePON1-NO was relatively
      stable: storage for 3days at 37 degrees C resulted in only 25% decomposition.
      This is the first report of PON1's S-nitrosylation via GSNO and HSA-NO. 

PMID- 24462771
TI  - The impact of drug-drug interactions on pulmonary arterial hypertension therapy.
AB  - In clinical practice, pulmonary arterial hypertension (PAH) requires co
      administration of multiple drugs to act on several pathogenic mechanisms; chronic
      pathologic conditions induce the onset of other concomitant diseases that need
      additional therapies. Combination treatment could exploit a synergism between
      administered drugs, increasing the effectiveness of the treatment and allowing
      dose reductions of the individual agents with a subsequent lower risk of
      toxicity. Conversely, concomitant administration of drugs may cause drug-drug
      interactions (DDIs), compromising treatment efficacy or increasing side effects,
      with a negative influence on disease progression. The choice of treatment is
      based on the fact that PAH is not caused by a single mechanism and that several
      syndromes, genetic abnormalities and environmental factors predispose to disease;
      therefore it is very likely that the use of treatments acting on a single pathway
      are not significantly effective. Moreover PAH is also frequently associated with
      other diseases that require concomitant clinical therapy. In this review we
      focused on the pharmacological treatment in PAH and related DDIs, evaluating
      alterations in drug transport, absorption, metabolism and excretion. This
      detailed analysis may be useful in clinical practice, as a better prediction of
      adverse events caused by DDIs in PAH improves the efficacy of combination
      therapy, resulting in reduced health care costs. 

PMID- 24462772
TI  - TRPC6 participates in the regulation of cytosolic basal calcium concentration in
      murine resting platelets.
AB  - Cytosolic-free Ca(2+) plays a crucial role in blood platelet function and is
      essential for thrombosis and hemostasis. Therefore, cytosolic-free Ca(2+)
      concentration is tightly regulated in this cell. TRPC6 is expressed in platelets,
      and an important role for this Ca(2+) channel in Ca(2+) homeostasis has been
      reported in other cell types. The aim of this work is to study the function of
      TRPC6 in platelet Ca(2+) homeostasis. The absence of TRPC6 resulted in an 18.73%
      decreased basal [Ca(2+)]c in resting platelets as compared to control cells.
      Further analysis confirmed a similar Ca(2+) accumulation in wild-type and TRPC6
      deficient mice; however, passive Ca(2+) leak rates from agonist-sensitive
      intracellular stores were significantly decreased in TRPC6-deficient platelets.
      Biotinylation studies indicated the presence of an intracellular TRPC6
      population, and subcellular fractionation indicated their presence on endoplasmic
      reticulum membranes. Moreover, the presence of intracellular calcium release in
      platelets stimulated with 1-oleoyl-2-acetyl-sn-glycerol further suggested a
      functional TRPC6 population located on the intracellular membranes surrounding
      calcium stores. However, coimmunoprecipitation assay confirmed the absence of
      STIM1-TRPC6 interactions in resting conditions. This findings together with the
      absence of extracellular Mn(2+) entry in resting wild-type platelets indicate
      that the plasma membrane TRPC6 fraction does not play a significant role in the
      maintenance of basal [Ca(2+)]c in mouse platelets. Our results suggest an active
      participation of the intracellular TRPC6 fraction as a regulator of basal
      [Ca(2+)]c, controlling the passive Ca(2+) leak rate from agonist-sensitive
      intracellular Ca(2+) stores in resting platelets. 

PMID- 24462773
TI  - CTGF increases drug resistance to paclitaxel by upregulating survivin expression
      in human osteosarcoma cells.
AB  - Osteosarcoma is the most common primary malignant tumor, and its treatments
      require more effective therapeutic approaches. Paclitaxel has a broad range of
      antitumor activities, including apoptosis-inducing effects. However, the majority
      of tumors in patients with advanced cancer eventually develop chemoresistance.
      Connective tissue growth factor (CTGF) is a secreted protein that modulates the
      invasiveness of certain human cancer cells by binding to integrins. However, the
      effect of CTGF in paclitaxel-mediated chemotherapy is unknown. Here, we report
      that the expression of CTGF in osteosarcoma patients was significantly higher
      than that of the CTGF expression in normal bone tissues. Overexpression of CTGF
      increased the resistance to paclitaxel-mediated cell apoptosis. In contrast,
      knockdown of CTGF expression by CTGF shRNA increased the chemotherapeutic effect
      of paclitaxel. In addition, CTGF increased resistance to paclitaxel-induced
      apoptosis through upregulation of survivin expression. Moreover, the AMP
      activated protein kinase (AMPK)-dependent nuclear factor kappa B (NF-kappaB)
      pathway mediated paclitaxel-increased chemoresistance and survivin expression. In
      a mouse xenograft model, overexpression of CTGF promoted resistance to
      paclitaxel. In contrast, knockdown of CTGF expression increased the therapeutic
      effect of paclitaxel in this model. In conclusion, our data indicate that CTGF
      might be a critical oncogene of human osteosarcoma involved in resistance to
      paclitaxel treatment. 

PMID- 24462774
TI  - Dissociated presenilin-1 and TACE processing of ErbB4 in lung alveolar type II
      cell differentiation.
AB  - Neuregulin (NRG) stimulation of ErbB4 signaling is important for type II cell
      surfactant synthesis. ErbB4 may mediate gene expression via a non-canonical
      pathway involving enzymatic cleavage releasing its intracellular domain (4ICD)
      for nuclear trafficking and gene regulation. The accepted model for release of
      4ICD is consecutive cleavage by Tumor necrosis factor alpha Converting Enzyme
      (TACE) and gamma-secretase enzymes. Here, we show that 4ICD mediates surfactant
      synthesis and its release by gamma-secretase is not dependent on previous TACE
      cleavage. We used siRNA to silence Presenilin-1 (PSEN-1) expression in a mouse
      lung type II epithelial cell line (MLE12 cells), and both siRNA knockdown and
      chemical inhibition of TACE. Knockdown of PSEN-1 significantly decreased baseline
      and NRG-stimulated surfactant phospholipid synthesis, expression of the
      surfactant proteins SP-B and SP-C, as well as 4ICD levels, with no change in
      ErbB4 ectodomain shedding. Neither siRNA knockdown nor chemical inhibition of
      TACE inhibited 4ICD release or surfactant synthesis. PSEN-1 cleavage of ErbB4 for
      non-canonical signaling through 4ICD release does not require prior cleavage by
      TACE. 

PMID- 24462777
TI  - Emerging pollutants in the environment: present and future challenges in
      biomonitoring, ecological risks and bioremediation.
AB  - Emerging pollutants reach the environment from various anthropogenic sources and
      are distributed throughout environmental matrices. Although great advances have
      been made in the detection and analysis of trace pollutants during recent
      decades, due to the continued development and refinement of specific techniques,
      a wide array of undetected contaminants of emerging environmental concern need to
      be identified and quantified in various environmental components and biological
      tissues. These pollutants may be mobile and persistent in air, water, soil,
      sediments and ecological receptors even at low concentrations. Robust data on
      their fate and behaviour in the environment, as well as on threats to ecological
      and human health, are still lacking. Moreover, the ecotoxicological significance
      of some emerging micropollutants remains largely unknown, because satisfactory
      data to determine their risk often do not exist. This paper discusses the fate,
      behaviour, (bio)monitoring, environmental and health risks associated with
      emerging chemical (pharmaceuticals, endocrine disruptors, hormones, toxins, among
      others) and biological (bacteria, viruses) micropollutants in soils, sediments,
      groundwater, industrial and municipal wastewaters, aquaculture effluents, and
      freshwater and marine ecosystems, and highlights new horizons for their
      (bio)removal. Our study aims to demonstrate the imperative need to boost research
      and innovation for new and cost-effective treatment technologies, in line with
      the uptake, mode of action and consequences of each emerging contaminant. We also
      address the topic of innovative tools for the evaluation of the effects of
      toxicity on human health and for the prediction of microbial availability and
      degradation in the environment. Additionally, we consider the development of
      (bio)sensors to perform environmental monitoring in real-time mode. This needs to
      address multiple species, along with a more effective exploitation of specialised
      microbes or enzymes capable of degrading endocrine disruptors and other
      micropollutants. In practical terms, the outcomes of these activities will build
      up the knowledge base and develop solutions to fill the significant innovation
      gap faced worldwide. 

PMID- 24462776
TI  - Metabolic brain activity suggestive of persistent pain in a rat model of
      neuropathic pain.
AB  - Persistent pain is a central characteristic of neuropathic pain conditions in
      humans. Knowing whether rodent models of neuropathic pain produce persistent pain
      is therefore crucial to their translational applicability. We investigated the
      spared nerve injury (SNI) model of neuropathic pain and the formalin pain model
      in rats using positron emission tomography (PET) with the metabolic tracer
      [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity
      suggestive of persistent pain. For the formalin model, under brief anesthesia we
      injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We
      then allowed the animals to awaken and observed pain behavior for 30min during
      the FDG uptake period. The rat was then anesthetized and placed in the scanner
      for static image acquisition, which took place between minutes 45 and 75 post
      tracer injection. A single reference rat brain magnetic resonance image (MRI) was
      used to align the PET images with the Paxinos and Watson rat brain atlas.
      Increased glucose metabolism was observed in the somatosensory region associated
      with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and
      cingulate cortex. Decreases were observed in the prelimbic cortex and
      hippocampus. Second, SNI rats were scanned 3weeks post-surgery using the same
      scanning paradigm, and region-of-interest analyses revealed increased metabolic
      activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats
      was scanned while anesthetized during the tracer uptake period, and the S1
      hindlimb increase was not observed. Increased brain activity in the somatosensory
      cortex of SNI rats resembled the activity produced with the injection of
      formalin, suggesting that the SNI model may produce persistent pain. The lack of
      increased activity in S1 hindlimb with general anesthetic demonstrates that this
      effect can be blocked, as well as highlights the importance of investigating
      brain activity in awake and behaving rodents. 

PMID- 24462775
TI  - Estrogen and the female heart.
AB  - Estrogen has a plethora of effects in the cardiovascular system. Studies of
      estrogen and the heart span human clinical trials and basic cell and molecular
      investigations. Greater understanding of cell and molecular responses to
      estrogens can provide further insights into the findings of clinical studies.
      Differences in expression and cellular/intracellular distribution of the two main
      receptors, estrogen receptor (ER) alpha and beta, are thought to account for the
      specificity and differences in responses to estrogen. Much remains to be learned
      in this area, but cellular distribution within the cardiovascular system is
      becoming clearer. Identification of GPER as a third ER has introduced further
      complexity to the system. 17beta-estradiol (E2), the most potent human estrogen,
      clearly has protective properties activating a signaling cascade leading to
      cellular protection and also influencing expression of the protective heat shock
      proteins (HSP). E2 protects the heart from ischemic injury in basic studies, but
      the picture is more involved in the whole organism and clinical studies. Here the
      complexity of E2's widespread effects comes into play and makes interpretation of
      findings more challenging. Estrogen loss occurs primarily with aging, but few
      studies have used aged models despite clear evidence of differences between the
      response to estrogen deficiency in adult and aged animals. Thus more work is
      needed focusing on the effects of aging vs. estrogen loss on the cardiovascular
      system. 

PMID- 24462778
TI  - Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1
      deficiency.
AB  - Lipoic acid metabolism defects are new metabolic disorders that cause
      neurological, cardiomuscular or pulmonary impairment. We report on a patient that
      presented with progressive neurological regression suggestive of an energetic
      disease, involving leukoencephalopathy with cysts. Elevated levels of glycine in
      plasma, urine and CSF associated with intermittent increases of lactate were
      consistent with a defect in lipoic acid metabolism. Support for the diagnosis was
      provided by pyruvate dehydrogenase deficiency and multiple mitochondrial
      respiratory chain deficiency in skin fibroblasts, as well as no lipoylated
      protein by western blot. Two mutations in the NFU1 gene confirmed the diagnosis.
      The p.Gly208Cys mutation has previously been reported suggesting a founder effect
      in Europe. 

PMID- 24462779
TI  - Optimized immobilization of lectins using self-assembled monolayers on
      polysilicon encoded materials for cell tagging.
AB  - Self-assembled monolayers (SAMs) have been used for the preparation of functional
      microtools consisting of encoded polysilicon barcodes biofunctionalized with
      proteins of the lectin family. These hybrid microtools exploit the lectins
      ability for recognizing specific carbohydrates of the cell membrane to give an
      efficient system for cell tagging. This work describes how the control of the
      methodology for SAM formation on polysilicon surfaces followed by lectin
      immobilization has a crucial influence on the microtool biofunction. Several
      parameters (silanization time, silane molar concentration, type of solvent or
      deposition methodology) have been studied to establish optimal function.
      Furthermore, silanes incorporating different terminal groups, such as aldehyde,
      activated ester or epoxide groups were tested in order to analyze their chemical
      coupling with the biomolecules, as well as their influence on the
      biofunctionality of the immobilized protein. Two different lectins - wheat germ
      agglutinin (WGA) and phytohemagglutinin (PHA-L) - were immobilized, because they
      have different and specific cell recognition behaviour and exhibit different cell
      toxicity. In this way we can assess the effect of intrinsic bulk toxicity with
      that of the cell compatibility once immobilized as well as the importance of cell
      affinity. A variety of nanometrical techniques were used to characterize the
      active surfaces, and lectin immobilization was quantified using ultraviolet
      visible absorption spectroscopy (UV-vis) and optical waveguide light mode
      spectroscopy (OWLS). Once the best protocol was found, WGA and PHA were
      immobilized on polysilicon coded barcodes, and these microtools showed excellent
      cell tagging on living mouse embryos when WGA was used.

PMID- 24462780
TI  - Strategy to provide a useful solution to effective delivery of
      dihydroartemisinin: development, characterization and in vitro studies of
      liposomal formulations.
AB  - Dihydroartemisinin is one of the most potent anticancer artemisinin-like
      compounds, able to induce cancer cell death by apoptotic pathways. Besides its
      effectiveness, it is a poorly water soluble drug with low bioavailability and low
      half-life (34-90 min), therefore, the development of new formulations of
      dihydroartemisinin to increase bioavailability is in great need. Conventional
      (P90G and cholesterol) and stealth liposomes (P90G; cholesterol and PE 18:0/18:0
      PEG 2000) to deliver dihydroartemisinin to cancer cells were developed for the
      first time. Both developed formulations show physical characteristics as drug
      carrier for parental administration and good values of encapsulation efficiency
      (71% conventional liposomes and 69% stealth liposomes). Physical and chemical
      stabilities were evaluated under storage condition and in presence of albumin.
      Cellular uptake efficiency of liposomes was determined by flow cytometry. Higher
      internalization occurred in the conventional liposomes rather than in the stealth
      liposomes suggesting that hydrophilic steric barrier of PEG molecules can reduce
      cellular uptake. Flow cytometry analysis was also used as an alternative
      technique for rapid size determination of liposomes. Cytotoxicity studies in the
      MCF-7 cell line confirmed the absence of toxicity in blank formulations
      suggesting liposomes may be a suitable carrier for delivery of DHA avoiding the
      use of organic solvents. Cytotoxicity of DHA and of both liposomal formulations
      was evaluated in the same cell line, confirming a modified release of DHA from
      vesicles after cellular uptake.

PMID- 24462781
TI  - RNAi mediates post-transcriptional repression of gene expression in fission yeast
      Schizosaccharomyces pombe.
AB  - RNA interference (RNAi) is a gene silencing mechanism conserved from fungi to
      mammals. Small interfering RNAs are products and mediators of the RNAi pathway
      and act as specificity factors in recruiting effector complexes. The
      Schizosaccharomyces pombe genome encodes one of each of the core RNAi proteins,
      Dicer, Argonaute and RNA-dependent RNA polymerase (dcr1, ago1, rdp1). Even though
      the function of RNAi in heterochromatin assembly in S. pombe is established, its
      role in controlling gene expression is elusive. Here, we report the
      identification of small RNAs mapped anti-sense to protein coding genes in fission
      yeast. We demonstrate that these genes are up-regulated at the protein level in
      RNAi mutants, while their mRNA levels are not significantly changed. We show that
      the repression by RNAi is not a result of heterochromatin formation. Thus, we
      conclude that RNAi is involved in post-transcriptional gene silencing in S.
      pombe. 

PMID- 24462782
TI  - Use of a resting hand orthosis for the hemiparetic hand after stroke.

PMID- 24462783
TI  - Accuracy of episodic autobiographical memory in children with early thyroid
      hormone deficiency using a staged event.
AB  - Autobiographical memory (AM) is a highly constructive cognitive process that
      often contains memory errors. No study has specifically examined AM accuracy in
      children with abnormal development of the hippocampus, a crucial brain region for
      AM retrieval. Thus, the present study investigated AM accuracy in 68 typically
      and atypically developing children using a staged autobiographical event, the
      Children's Autobiographical Interview, and structural magnetic resonance imaging.
      The atypically developing group consisted of 17 children (HYPO) exposed during
      gestation to insufficient maternal thyroid hormone (TH), a critical substrate for
      hippocampal development, and 25 children with congenital hypothyroidism (CH), who
      were compared to 26 controls. Groups differed significantly in the number of
      accurate episodic details recalled and proportion accuracy scores, with controls
      having more accurate recollections of the staged event than both TH-deficient
      groups. Total hippocampal volumes and anterior hippocampal volumes were
      positively correlated with proportion accuracy scores, but not total accurate
      episodic details, in HYPO and CH. In addition, greater severity of TH deficiency
      predicted lower proportion accuracy scores in both HYPO and CH. Overall, these
      results indicate that children with early TH deficiency have deficits in AM
      accuracy and that the anterior hippocampus may play a particularly important role
      in accurate AM retrieval. 

PMID- 24462784
TI  - A pharmacokinetic and pharmacodynamic study of drug-drug interaction between
      ginsenoside Rg1, ginsenoside Rb1 and schizandrin after intravenous administration
      to rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg1, ginsenoside Rb1 and schizandrin
      are main bioactive components from Panax ginseng and Schisandra chinensis. They
      have been found in many prescriptions of Traditional Chinese Medicines (TCM) and
      proven to be effective for prevention and treatment of cardiovascular disease. It
      is valuable to investigate their pharmacokinetic and pharmacodynamic behavior and
      potential synergistic effect for better drug development and clinical
      application. MATERIALS AND METHODS: Pharmacokinetic and nitric oxide (NO) release
      pharmacodynamic drug-drug interactions of ginsenoside Rg1, ginsenoside Rb1 and
      schisandrin were studied after intravenous administration of each compound with
      the dose of 10 mg/kg and their mixture with the total dose of 10 mg/kg to
      isoproterenol (ISO)-induced myocardial ischemia rats. Drug concentrations in
      serum were determined using LC-MS method. Nitrite and nitrate (NOx(-)), the
      predominant oxidation product of NO in serum was used as an effective marker and
      quantitated by the method of high-performance liquid chromatography coupled with
      fluorescence detection (HPLC-FL). The main pharmacokinetic parameters of
      T(1/2beta), MRT(0-infinity), Vd, Cl, and AUC, and the main pharmacodynamic
      parameters of Cmax, Tmax and AUEC were calculated by non-compartment model.
      RESULTS: The results indicated ginsenoside Rb1 and (or) schisandrin in mixture
      could significantly postpone the elimination of ginsenoside Rg1 in rat serum. Co
      administration of three compounds markedly increased the systemic exposure level
      of each compound in vivo. Ginsenoside Rg1 and ginsenoside Rb1 had the effect of
      inducing real-time NO release in rats concentration dependently. Schisandrin had
      no effect of inducing real-time NO release in this study. The mixture of
      ginsenoside Rg1, Rb1 and schisandrin administration exhibited synergistic effect
      of inducing NO release in ISO treated rats. CONCLUSIONS: The result obtained from
      this study suggested pharmacokinetic and pharmacodynamic drug-drug interactions
      between ginsenoside Rg1, Rb1 and schisandrin. The study provided valuable
      information for drug development and clinical application of TCM.

PMID- 24462785
TI  - Effects of Juglans regia L. leaf extract on hyperglycemia and lipid profiles in
      type two diabetic patients: a randomized double-blind, placebo-controlled
      clinical trial.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Juglans regia L. leaf has been traditionally
      used for treatment of diabetes mellitus in Iran. But yet, no controlled human
      study has determined its efficacy in diabetic patients. The present study was
      designed to investigate the effects of the Juglans regia leaf extract on
      hyperglycemia and lipid profiles in type II diabetic patients. MATERIALS AND
      METHOD: Total 61 patients, suffering from type II diabetes with fasting blood
      glucose (FBG) between 150 and 200mg/dL, glycated hemoglobin (HbA1c) between 7%
      and 9% and aged between 40 and 60 years were selected, and randomly divided in to
      two groups of Juglans regia and placebo. First group received 100mg Juglans regia
      leaf extract in capsules form two times a day for 3 months and other group
      received 100mg placebo capsule with the same dosage. The standard anti-diabetic
      therapy (metformin and glibenclamide, and nutritional regimen) was continued in
      both groups. At the baseline and after three months the FBG, insulin, HbA1c,
      cholesterol, triglyceride, HDL, LDL and liver and renal function tests were
      determined. In addition general satisfaction with the treatment was identified
      using health questionnaires. RESULTS: The results indicated that FBG, HbA1c,
      total cholesterol and triglyceride levels in Juglans regia treated patients
      significantly decreased compared with the baseline and with placebo group.
      Patients in Juglans regia group were significantly satisfied with Juglans regia
      treatment compared with the placebo group. No liver, kidney and other side
      effects were observed in the groups, except more GI events (specially a mild
      diarrhea) associated with extract treatment at the beginning of the study.
      CONCLUSION: In conclusion, treatment of type II diabetic patients with 100mg
      Juglans regia leaf extract two times a day for three months improves lipid
      profile and glycemic control without any tangible adverse effects.

PMID- 24462787
TI  - Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting
      antioxidant signaling pathways.
AB  - Cardiovascular disease is the primary cause of morbidity and mortality among the
      diabetic population. Both experimental and clinical evidence suggest that
      diabetic subjects are predisposed to a distinct cardiomyopathy, independent of
      concomitant macro- and microvascular disorders. 'Diabetic cardiomyopathy' is
      characterized by early impairments in diastolic function, accompanied by the
      development of cardiomyocyte hypertrophy, myocardial fibrosis and cardiomyocyte
      apoptosis. The pathophysiology underlying diabetes-induced cardiac damage is
      complex and multifactorial, with elevated oxidative stress as a key contributor.
      We now review the current evidence of molecular disturbances present in the
      diabetic heart, and their role in the development of diabetes-induced impairments
      in myocardial function and structure. Our focus incorporates both the
      contribution of increased reactive oxygen species production and reduced
      antioxidant defenses to diabetic cardiomyopathy, together with modulation of
      protein signaling pathways and the emerging role of protein O-GlcNAcylation and
      miRNA dysregulation in the progression of diabetic heart disease. Lastly, we
      discuss both conventional and novel therapeutic approaches for the treatment of
      left ventricular dysfunction in diabetic patients, from inhibition of the renin
      angiotensin-aldosterone-system, through recent evidence favoring supplementation
      of endogenous antioxidants for the treatment of diabetic cardiomyopathy. Novel
      therapeutic strategies, such as gene therapy targeting the phosphoinositide 3
      kinase PI3K(p110alpha) signaling pathway, and miRNA dysregulation, are also
      reviewed. Targeting redox stress and protective protein signaling pathways may
      represent a future strategy for combating the ever-increasing incidence of heart
      failure in the diabetic population. 

PMID- 24462786
TI  - Premature menopause and risk of neurological disease: basic mechanisms and
      clinical implications.
AB  - Since basic scientific studies in the 1990s revealed dramatic gender differences
      in neurological damage from cerebral ischemia, significant evidence has
      accumulated for a neuroprotective role of ovarian-derived 17beta-Estradiol (E2).
      Intriguingly, observational studies have further suggested that early and
      prolonged loss of ovarian E2 (premature menopause) leads to a doubled lifetime
      risk for dementia and a fivefold increased risk of mortality from neurological
      disorders, but some controversy remains. Here, we briefly summarize and analyze
      clinical cohort studies assessing the detrimental neurological outcomes of
      premature menopause. Furthermore, we discuss current basic science studies
      elucidating the molecular mechanisms underlying the enhanced risk of neurological
      disease in prematurely menopausal women and the "window of opportunity" for
      estrogen benefit. Finally, we highlight four critical issues in the field that
      require collaboration between basic scientists and clinicians for successful
      resolution, with the ultimate goal of maintaining optimal neurological health in
      prematurely menopausal women. 

PMID- 24462791
TI  - Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage
      forms using a modeling and simulation approach coupled with biorelevant
      dissolution testing: case example diclofenac sodium.
AB  - The objective of this research was to characterize the dissolution profile of a
      poorly soluble drug, diclofenac, from a commercially available multiple-unit
      enteric coated dosage form, Diclo-Puren(r) capsules, and to develop a predictive
      model for its oral pharmacokinetic profile. The paddle method was used to obtain
      the dissolution profiles of this dosage form in biorelevant media, with the
      exposure to simulated gastric conditions being varied in order to simulate the
      gastric emptying behavior of pellets. A modified Noyes-Whitney theory was
      subsequently fitted to the dissolution data. A physiologically-based
      pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using
      STELLA(r) software and coupled with the biorelevant dissolution profiles in order
      to simulate the plasma concentration profiles of diclofenac from Diclo-Puren(r)
      capsule in both the fasted and fed state in humans. Gastric emptying kinetics
      relevant to multiple-units pellets were incorporated into the PBPK model by
      setting up a virtual patient population to account for physiological variations
      in emptying kinetics. Using in vitro biorelevant dissolution coupled with in
      silico PBPK modeling and simulation it was possible to predict the plasma profile
      of this multiple-unit formulation of diclofenac after oral administration in both
      the fasted and fed state. This approach might be useful to predict variability in
      the plasma profiles for other drugs housed in multiple-unit dosage forms. 

PMID- 24462790
TI  - The interplay of pain-related self-efficacy and fear on functional outcomes among
      youth with headache.
AB  - Pain-related self-efficacy and pain-related fear have been proposed as opposing
      predictors of pain-related functional outcomes in youth with chronic pain. Self
      efficacy is a potential resiliency factor that can mitigate the influence that
      pain-related fear has on outcomes in youth with chronic pain. Drawing from
      theoretical assertions tested among adults with chronic pain, this study aimed to
      determine whether pain-related self-efficacy mediates the adverse influence of
      pain-related fear on functional outcomes in a sample of youth with chronic
      headache. In a cross-sectional design of 199 youth with headache, self-efficacy
      was strongly associated with fear, disability, school impairment, and depressive
      symptoms. Pain intensity and self-efficacy were only modestly related, indicating
      that level of pain has less influence on one's confidence functioning with pain.
      Self-efficacy partially mediated relationships between pain-related fear and both
      functional disability and school functioning but did not mediate the relationship
      between pain-related fear and depressive symptoms. These results suggest that
      confidence in the ability to function despite pain and fear avoidance each
      uniquely contributes to pain-related outcomes in youth with chronic headache.
      These results further suggest that treatment for chronic headache in youth must
      focus not only on decreasing pain-related fear but also on enhancing a patient's
      pain-related self-efficacy. PERSPECTIVE: Pain-related self-efficacy is an
      important resiliency factor impacting the influence of pain-related fear on
      functional disability and school functioning in youth with headache. Enhancing
      self-efficacy may be a key mechanism for improving behavioral outcomes.
      Clinicians can reduce pain-related fear and enhance pain-related self-efficacy
      through interventions that encourage accomplishment and self-confidence.

PMID- 24462789
TI  - The complete picture of changing pediatric inflammatory bowel disease incidence
      in Spain in 25 years (1985-2009): the EXPERIENCE registry.
AB  - OBJECTIVES: A growing incidence of pediatric IBD (PIBD) in southern Europe has
      been recently reported. The SPIRIT registry (1996-2009) confirmed these
      tendencies in Spain. Our aim is to obtain data from 1985 to 1995 and describe the
      complete picture of PIBD presentation changes in Spain in the last 25years.
      METHODS: A retrospective survey of incident PIBD in the period 1985-1995 was
      performed. Patients' data were obtained from the hospitals' databases and
      compared with the published data from the 1996 to 2009 period. Seventy-eight IBD
      reference centers took part in this survey. RESULTS: Data from 495 patients were
      obtained: 278 CD (56.2%), 198 UC (40%), and 19 IBDU (3.8%); 51.7% were female,
      with higher predominance both in UC (58.6%) and in IBDU (57.9%), but not in CD
      (46.4%). Median (IQR) age at diagnosis was 12.9 (10.0-15.7) years, with
      significant differences among IBD subtypes: CD: 13.1 (10.8-16.0) vs UC: 12.4 (9.4
      15.1) vs IBDU: 7.5 (3.0-13.0) (p<=0.001). These results are significantly
      different to the ones in the SPIRIT registry, with a higher proportion of IBDU,
      younger age and male predominance. The data from both periods taken together give
      a complete picture of a 25-year period. An annual increase of incident patients
      was observed, with a ten-fold increase over this period. CONCLUSION: These data
      extend the epidemiological trends to a full 25-year period (1985-2009). PIBD
      incidence in Spain has experienced a sixteen-fold increase. The IBD subtype,
      localization of the affected segment, age- and sex distribution observed are in
      accordance with our previously published ones of 1996-2009.

PMID- 24462788
TI  - Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet.
AB  - The traditional diet in Okinawa is anchored by root vegetables (principally sweet
      potatoes), green and yellow vegetables, soybean-based foods, and medicinal
      plants. Marine foods, lean meats, fruit, medicinal garnishes and spices, tea,
      alcohol are also moderately consumed. Many characteristics of the traditional
      Okinawan diet are shared with other healthy dietary patterns, including the
      traditional Mediterranean diet, DASH diet, and Portfolio diet. All these dietary
      patterns are associated with reduced risk for cardiovascular disease, among other
      age-associated diseases. Overall, the important shared features of these healthy
      dietary patterns include: high intake of unrefined carbohydrates, moderate
      protein intake with emphasis on vegetables/legumes, fish, and lean meats as
      sources, and a healthy fat profile (higher in mono/polyunsaturated fats, lower in
      saturated fat; rich in omega-3). The healthy fat intake is likely one mechanism
      for reducing inflammation, optimizing cholesterol, and other risk factors.
      Additionally, the lower caloric density of plant-rich diets results in lower
      caloric intake with concomitant high intake of phytonutrients and antioxidants.
      Other shared features include low glycemic load, less inflammation and oxidative
      stress, and potential modulation of aging-related biological pathways. This may
      reduce risk for chronic age-associated diseases and promote healthy aging and
      longevity. 

PMID- 24462792
TI  - Biodegradable magnetic calcium phosphate nanoformulation for cancer therapy.
AB  - We fabricated a magnetic calcium phosphate nanoformulation by the
      biomineralization of calcium phosphate on the surface of magnetic nanoparticles
      with abundant amino groups, and thus the inorganic layer of calcium phosphate can
      improve the biocompatibility and simultaneously the magnetic iron oxide can
      maintain the magnetic targeting function. Two types of anticancer drug models,
      doxorubicin hydrochloride and DNA, were entrapped in these nanocarriers,
      respectively. This delivery system displayed high pH sensitivity in drug
      controlled release profile as the dissolution of CaP under acid pH condition.
      Magnetofection was performed to investigate the intracellular uptake and the anti
      proliferative effect of tumor cells in the presence of an external magnet. The
      transfection of the DNA-loaded magnetic system in A549 and HepG2 tumor cells
      demonstrated that the magnetic nanoformulation could enhance the transfection
      efficiency to 30% with an applied external magnetic field. 

PMID- 24462793
TI  - Development and characterization of functionalized niosomes for brain targeting
      of dynorphin-B.
AB  - A niosomal formulation, functionalized with N-palmitoylglucosamine, was developed
      as potential brain targeted delivery system of dynorphin-B. In fact, this
      endogenous neuropeptide, selective agonist of k opioid receptors, is endowed with
      relevant pharmacological activities on the central nervous system, including a
      marked antinociceptive effect, but is unable to cross the blood brain barrier
      (BBB), thus requiring intracerebroventricular administration. Statistical design
      of experiments was utilized for a systematic evaluation of the influence of
      variations of the relative amounts of the components of the vesicle membrane
      (Span 60, cholesterol and SolulanC24) on vesicle mean diameter, polydispersity
      index and drug entrapment efficiency, chosen as the responses to optimize. A
      Scheffe simplex-centroid design was used to obtain the coefficients of the
      postulated mathematical model. The study of the response surface plots revealed
      that variations of the considered factors had different effects on the selected
      responses. The desirability function enabled for finding the optimal mixture
      composition, which represented the best compromise to simultaneously optimize all
      the three responses. The experimental values obtained with the optimized
      formulation were very similar to the predicted ones, proving the validity of the
      proposed regression model. The optimized niosomal formulation of dynorphin-B
      administered intravenously to mice (100mg/kg) showed a pronounced antinociceptive
      effect, significantly higher (P<0.05) than that given by i.v. administration of
      the simple solution of the peptide at the same concentration, proving its
      effectiveness in enabling the peptide brain delivery. These positive results
      suggest that the proposed approach could be successfully extended to other neuro
      active peptides exerting a strong central action, even at low doses, but unable
      to cross the BBB. 

PMID- 24462794
TI  - Agitation-induced aggregation and subvisible particulate formation in model
      proteins.
AB  - The kinetics of agitation-induced subvisible particle formation was investigated
      for a few model proteins - human serum albumin (HSA), hen egg white lysozyme
      (HEWL), and a monoclonal antibody (IgG2). Experiments were carried out for the
      first time under relatively low protein concentration and low agitation speed to
      investigate the details of subvisible particle formation at the initial phase of
      aggregation (<2%) process. Upon agitation, both soluble higher molecular mass
      species (HMMS) and subvisible particles (SbVPs) formed at different rates, and
      via different mechanisms. Agitation enhanced exposure of hydrophobic sites in HSA
      but did not cause detectable structural changes in HEWL and IgG2. SbVPs from HSA
      partially dissociates in a neutral pH buffer (SEC mobile phase) but does not upon
      dilution in the same formulation buffer. Opposite results were obtained for SbVPs
      from IgG2 and HEWL. Neither the relative hydrophobic surface area nor the Tm of
      the model proteins seems to be an indicator of tendency for agitation-mediated
      SbVP formation. Taken together, our data suggests that agitation-induced SbVP
      formation can occur through different mechanisms and can vary, depending on the
      protein and solution conditions. 

PMID- 24462795
TI  - Exploring innovative ways to conduct coverage surveys for neglected tropical
      diseases in Malawi, Mali, and Uganda.
AB  - Currently, a 30-cluster survey to monitor drug coverage after mass drug
      administration for neglected tropical diseases is the most common methodology
      used by control programs. We investigated alternative survey methodologies that
      could potentially provide an estimation of drug coverage. Three alternative
      survey methods (market, village chief, and religious leader) were conducted and
      compared to the 30-cluster method in Malawi, Mali, and Uganda. In Malawi, drug
      coverage for the 30-cluster, market, village chief, and religious leader methods
      were 66.8% (95% CI 60.3-73.4), 74.3%, 76.3%, and 77.8%, respectively. In Mali,
      results for round 1 were 62.6% (95% CI 54.4-70.7), 56.1%, 74.8%, and 83.2%, and
      57.2% (95% CI 49.0-65.4), 54.5%, 72.2%, and 73.3%, respectively, for round 2.
      Uganda survey results were 65.7% (59.4-72.0), 43.7%, 67.2%, and 77.6%
      respectively. Further research is needed to test different coverage survey
      methodologies to determine which survey methods are the most scientifically
      rigorous and resource efficient. 

PMID- 24462796
TI  - Toxic and therapeutic effects of Nifurtimox and Benznidazol on Trypanosoma cruzi
      ex vivo infection of human placental chorionic villi explants.
AB  - Nifurtimox (Nfx) and Benznidazole (Bnz) are the only available drugs in use for
      the treatment of Chagas disease. These drugs are recommended but not fully
      validated in evidence-based medicine and reports about the differential toxicity
      of both drugs are controversial. Here, we evaluated the toxic and therapeutic
      effects of Nfx and Bnz on human placental chorionic villi explants (HPCVE) during
      ex vivo infection of Trypanosoma cruzi, performing histopathological,
      histochemical, immunohistochemical as well as immunofluorescence analysis of the
      tissue. Additionally, we determined the effect of both drugs on parasite load by
      real time PCR. Bnz prevents the parasite induced tissue damage in ex vivo
      infected HPCVE compared to Nfx, which is toxic per se. The presence of T. cruzi
      antigens and DNA in infected explants suggests that these drugs do not impair
      parasite invasion into the HPCVE. Additionally, our results confirm reports
      suggesting that Bnz is less toxic than Nfx and support the need for the
      development of more effective and better-tolerated drugs. 

PMID- 24462797
TI  - Multi-nanomaterial electrochemical biosensor based on label-free graphene for
      detecting cancer biomarkers.
AB  - Developing a rapid, accurate and sensitive electrochemical biosensor for
      detecting cancer biomarkers is important for early detection and diagnosis. This
      work reports an electrochemical biosensor based on a graphene (GR) platform which
      is made by CVD, combined with magnetic beads (MBs) and enzyme-labeled antibody
      gold nanoparticle bioconjugate. MBs coated with capture antibodies (Ab1) were
      attached to GR sheets by an external magnetic field, to avoid reducing the
      conductivity of graphene. Sensitivity was also enhanced by modifying the gold
      nanoparticles (AuNPs) with horseradish peroxidase (HRP) and the detection
      antibody (Ab2), to form the conjugate Ab2-AuNPs-HRP. Electron transport between
      the electrode and analyte target was accelerated by the multi-nanomaterial, and
      the limit of detection (LOD) for carcinoembryonic antigen (CEA) reached 5 ng mL(
      1). The multi-nanomaterial electrode GR/MBs-Ab1/CEA/Ab2-AuNPs-HRP can be used to
      detect biomolecules such as CEA. The EC biosensor is sensitive and specific, and
      has potential in the detection of disease markers.

PMID- 24462798
TI  - Sex-related differences in muscle deoxygenation during ramp incremental exercise:
      response to Peltonen et al.

PMID- 24462799
TI  - Diphtheria toxin-based bivalent human IL-2 fusion toxin with improved efficacy
      for targeting human CD25(+) cells.
AB  - Regulatory T cells (Treg) constitute a major inhibitory cell population which
      suppresses immune responses. Thus, Treg have proven to be key players in the
      induction of transplantation tolerance, protection from autoimmune disease and
      prevention of the development of effective anti-tumor immune reactions. Treg
      express high levels of the high affinity interleukin-2 receptor (IL-2R)
      consisting of IL-2Ralpha (CD25) together with IL-2Rbeta (CD122) and the common
      gamma-chain (CD132). An effective reagent capable of depleting Treg in vivo would
      facilitate better cancer treatment and allow mechanistic studies of the role of
      Treg in transplantation tolerance and the development of autoimmune disease. In
      this study, we have developed a novel bivalent human IL-2 fusion toxin along with
      an Ontak(r)-like monovalent human IL-2 fusion toxin and compared the functional
      ability of these reagents in vitro. Here we show that genetically linking two
      human IL-2 domains in tandem, thereby generating a bivalent fusion toxin, results
      in significantly improved capacity in targeting human CD25(+) cells in vitro.
      Binding analysis by flow cytometry showed that the bivalent human IL-2 fusion
      toxin has notably increased affinity for human CD25(+) cells. In vitro functional
      analysis demonstrated that the bivalent isoform has an increased potency of
      approximately 2 logs in inhibiting cellular proliferation and protein synthesis
      in human CD25(+) cells compared to the monovalent human IL-2 fusion toxin.
      Additionally, we performed two inhibition assays in order to verify that the
      fusion toxins target the cells specifically through binding of the human IL-2
      domain of the fusion toxin to the human IL-2 receptor on the cell surface. These
      results demonstrated that 1) both monovalent and bivalent human IL-2 fusion
      toxins are capable of blocking the binding of biotinylated human IL-2 to human
      CD25 by flow cytometry; and 2) human IL-2 blocked the fusion toxins from
      inhibiting protein synthesis and cellular proliferation in vitro, thus confirming
      that the human IL-2 fusion toxins target the cells specifically through binding
      to the human IL-2 receptor. We believe that the bivalent human IL-2 fusion toxin
      will be a more potent, and therefore, more optimal agent than the current
      clinically-used monovalent fusion toxin (denileukin diftitox, Ontak(r)) for in
      vivo depletion of Treg. 

PMID- 24462801
TI  - A pregnant mouse model for the vertical transmission of Brucella melitensis.
AB  - Abortion is the major clinical sign of brucellosis in animals but little is known
      about the underlying mechanisms. This study was designed to evaluate a pregnant
      mouse model for the vertical transmission of Brucella melitensis using four
      infectious doses: 10(3) colony-forming units (CFU), 10(4) CFU, 10(5) CFU, and
      10(6) CFU. During the experimental period, no instances of abortion were
      recorded, but stillbirths were observed in the groups infected with doses of
      10(4) CFU and higher. Regardless of whether the fetuses were stillborn or alive,
      transmission of bacteria to the fetus and bacterial replication in the cytoplasm
      of placental trophoblast giant cells were detected. A higher degree of bacterial
      colonization was found in the placenta than in the spleen or fetus. Doses of
      10(5) CFU of B. melitensis or higher produced a severe, necrotizing placentitis
      similar to the pathological damage observed in ruminants. The data suggest that
      experimental murine brucellosis resembles ruminant brucellosis and represents a
      potential model for studying the pathogenic mechanisms of B. melitensis. 

PMID- 24462800
TI  - Hapten-specific naive B cells are biomarkers of vaccine efficacy against drugs of
      abuse.
AB  - Vaccination against drugs of abuse shows efficacy in animal models, yet few
      subjects achieve effective serum antibody titers in clinical studies. A barrier
      to translation is the lack of pre-vaccination screening assays that predict the
      most effective conjugate vaccines or subjects amenable to vaccination. To address
      this obstacle, we developed a fluorescent antigen-based enrichment method paired
      with flow cytometry to characterize hapten-specific B cells. Using this approach,
      we studied naive and activated B cells specific for structurally-related model
      haptens based on derivatization of the morphinan structure at the C6 position on
      oxycodone or at the C8 position on hydrocodone, and showing different pre
      clinical efficacy against the prescription opioid oxycodone. Prior to
      vaccination, naive B cells exhibited relatively higher affinity for the more
      effective C6-derivatized oxycodone-based hapten (6OXY) and the 6OXY-specific
      naive B cell population contained a higher number of B cells with greater
      affinity for free oxycodone. Higher affinity of naive B cells for hapten or
      oxycodone reflected greater efficacy of vaccination in blocking oxycodone
      distribution to brain in mice. Shortly after immunization, activated hapten
      specific B cells were detected prior to oxycodone-specific serum antibodies and
      provided earlier evidence of vaccine failure or success. Analysis of hapten
      specific naive and activated B cells may aid rational vaccine design and provide
      screening tools to predict vaccine clinical efficacy against drugs of abuse or
      other small molecules. 

PMID- 24462803
TI  - Study of the reduced field-of-view diffusion-weighted imaging of the breast.
AB  - BACKGROUND: This study aimed to compare the imaging quality, apparent diffusion
      coefficient (ADC) values, and application values between reduced field-of-view
      diffusion-weighted imaging (rFOV DWI) and single-shot echo-planar-imaging
      diffusion-weighted imaging (SS-EPI DWI) of breast tissue. PATIENTS AND METHODS:
      For 87 cases (75 with normal breast tissue, 12 with mammary cancer), breasts were
      scanned with SS-EPI DWI and rFOV DWI (b values, 800 s/mm(2)). Image quality and
      ADC values of breast tissue images were compared between SS-EPI DWI and rFOV DWI.
      RESULTS: The average image quality score for the 87 cases was 4.73 in rFOV DWI
      and 3.62 in SS-EPI DWI. The difference was statistically significant (P < .01).
      The resolution of rFOV DWI was 2.25 mm * 1.23 mm, which was higher than the
      resolution of SS-EPI DWI (2.25 mm * 2.25 mm). The mean ADC value of 75 cases with
      normal breast tissue was 1.696 * 10(-3) mm(2)/s by rFOV DWI and 1.832 * 10(-3)
      mm(2)/s by SS-EPI DWI, and the difference was statistically significant (P <
      .01). The mean ADC value for the 12 cases with breast cancer was 1.065 * 10(-3)
      mm(2)/s by rFOV DWI and 1.192 * 10(-3) mm(2)/s by SS-EPI DWI, which was a
      statistically significant difference (P < .05). CONCLUSION: rFOV DWI presented
      images with higher resolution and less distortion than SS-EPI DWI, and this
      difference may be helpful in disease diagnosis.

PMID- 24462802
TI  - Dickkopf-1 as a mediator and novel target in malignant bone disease.
AB  - Bone metastases are a common problem of many malignancies, including myeloma,
      breast and prostate cancer. The Wnt inhibitor Dickkopf-1 has been shown to be
      involved in the process of bone lesions by impairing osteoblast activity. This
      review will focus on the role of Dickkopf-1 as a mediator of malignant bone
      disease and discuss its potential as a novel therapeutic target. 

PMID- 24462804
TI  - Transitional cell carcinoma of the ovary: a case-control study.
AB  - OBJECTIVES: The aim of this study is to compare response to chemotherapy and
      survival between patients with transitional call carcinoma of the ovary (TCCO)
      and papillary serous ovarian cancer (PSOC). METHODS: We identified women with
      both pure and mixed TCCO who were treated between 2000 and 2010. Each case was
      matched to two women with PSOC by age, grade, stage, and year of diagnosis.
      Correlation between categorical variables was assessed with chi square test. The
      Kaplan-Meier survival analysis was used to generate overall survival data (OS).
      Factors predictive of outcome were compared using the log-rank test and Cox
      proportional hazards model. RESULTS: Eighty-one women diagnosed with TCCO were
      selected as cases and compared to 162 controls. Women with TCCO had a lower rate
      of platinum resistance compared to controls (9% vs. 25%; p=0.01). When
      multivariate logistic regression was used to control for other factors
      independently associated with platinum resistance, patients with TCCO had a
      significantly lower risk of platinum resistance compared to PSOC. Median
      progression-free survival was not significantly different (27 months vs. 22
      months; p=0.15) for women with TCCO and PSOC, respectively. Median OS, however,
      was significantly different at 83 months vs. 52 months for the TCCO and PSOC
      groups, respectively (p=0.01). A Cox proportional hazards model identified
      optimal cytoreduction, transitional cell histology, age, stage, and platinum and
      paclitaxel chemotherapy as independent predictors of OS. CONCLUSIONS: Patients
      with TCCO are less likely to demonstrate resistance to platinum chemotherapy and
      have improved overall survival when compared to patients with PSOC.

PMID- 24462805
TI  - Mouse CMV infection delays antibody class switch upon an unrelated virus
      challenge.
AB  - Poor immune protection upon vaccination is a critical determinant of
      immunosenescence. Latent Cytomegalovirus (CMV) infection has been associated with
      poor antibody responses to vaccination, but a causative role for CMV in the poor
      immune response requires experimental evidence and thus could not be confirmed in
      clinical studies. To test the hypothesis that latent CMV infection causes poor
      antibody responses, we infected young or adult mice with mouse CMV and challenged
      them with Vesicular stomatitis virus (VSV) at 15 or 18months of age. Latent, but
      not primary infection with mouse CMV resulted in diminished neutralizing titers
      of the serum IgG fraction at day 7 post challenge, which recovered by day 14 post
      challenge. This phenomenon was specific for mice infected with mouse CMV, but not
      mice infected with other herpesviruses, like murine herpesvirus-68 or herpes
      simplex virus type 1, or mice infected with non-persistent viruses, such as
      influenza or Vaccinia virus. Hence, our data indicate a delay in IgG class-switch
      that was specific for the CMV infection. Herpesviral infections did not change
      the B-cell memory compartment, and increased the size of the effector-memory
      subset of blood CD4 T-cells only when administered in combination. Furthermore,
      CD4 T-cell response to VSV infection was maintained in latently infected mice.
      Therefore, our results argue that latent CMV infection impairs B-cell, but not T
      cell responses to a challenge with VSV and delays antibody class-switch by a
      mechanism which may be independent of T-cell help. 

PMID- 24462806
TI  - The effect of knee joint angle on plantar flexor power in young and old men.
AB  - Human adult aging is associated with a loss of strength, contractile velocity and
      hence, power. The principal plantar flexors, consisting of the bi-articular
      gastrocnemeii and the mono-articular soleus, appear to be affected differently by
      the aging process. However, the age-related effect of knee joint angle on the
      torque-angular velocity relationship and power production of this functionally
      important muscle group is unknown. The purpose was to determine whether flexing
      the knee, thereby reducing the gastrocnemius contribution to plantar flexion,
      would exacerbate the age-related decrements in plantar flexion power, or shift
      the torque-angular velocity relationship differently in older compared with young
      men. Neuromuscular properties were recorded from 10 young (~25 y) and 10 old (~78
      y) men with the knee extended (170 degrees ) and flexed (90 degrees ), in a
      randomized order. Participants performed maximal voluntary isometric contractions
      (MVCs), followed by maximal velocity-dependent shortening contractions at pre-set
      loads, ranging from 15 to 75% MVC. The young men were ~20-25% stronger, ~12%
      faster and ~30% more powerful than the old for both knee angles (P<0.05). In both
      age groups, isometric MVC torque was ~17% greater in the extended than flexed
      knee position, with no differences in voluntary activation (>95%). The young men
      produced 7-12% faster angular velocities in the extended knee position for loads
      <=30% MVC, but no differences at higher loads; whereas there were no detectable
      differences in angular velocity between knee positions in the old across all
      relative loads. For both knee angles, young men produced peak power at 43.3+/
      9.0% MVC, whereas the old men produced peak power at 54.8+/-7.9% MVC. These data
      indicate that the young, who have faster contracting muscles compared with the
      old, can rely more on velocity than torque for generating maximal power.

PMID- 24462807
TI  - Differentiation of Cronobacter spp. by tryptic digestion of the cell suspension
      followed by MALDI-TOF MS analysis.
AB  - Intact cell MALDI-TOF mass spectrometry is a rapid tool for the identification
      and classification of microorganisms, now widely used even in clinical
      laboratories. However, its distinctive power is not sufficient for some closely
      related species. The genus Cronobacter, formerly known as Enterobacter sakazakii,
      contains such species. In this work, a new method for the differentiation of five
      Cronobacter species is presented involving the tryptic digestion of cytoplasmatic
      proteins followed by MALDI mass spectrometry analysis. A database was developed
      for use in Bruker Biotyper software including 52 reference spectra and tested on
      a set of 45 samples with an overall accuracy of about 80%. The possibility of
      measurement automation and the short time and low cost requirements of this
      method compared to those of biochemical tests or PCR methods make it a
      supplementary option to intact cell MALDI, providing additional information about
      the differentiation of problematic species. 

PMID- 24462808
TI  - Evaluation of BMPA, MWY, GVPC and BCYE media for the isolation of Legionella
      species from respiratory samples.
AB  - Culture media performance is a critical factor in the isolation of Legionellae
      from respiratory samples. We showed that BMPA and MWY media yielded significantly
      higher isolation rates than GVPC and BCYE media in regard to performance with
      samples that harbored low Legionella inocula and high contamination levels. 

PMID- 24462809
TI  - Insulin-derived amyloidosis and poor glycemic control: a case series.
AB  - OBJECTIVES: Insulin-derived amyloidosis is a rare skin-related complication of
      insulin therapy. The purpose of this study was to show the effects of insulin
      derived amyloidosis on blood glucose levels, insulin dose requirements, and
      insulin absorption. METHODS: Seven patients were found to have insulin-derived
      amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical
      characteristics and insulin therapy of the 7 patients were investigated. Insulin
      absorption was studied by comparing the serum insulin levels after insulin
      injections into insulin-derived amyloidosis sites versus injections into normal
      sites in 4 patients. RESULTS: When the insulin-derived amyloidosis was
      discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin
      dose was 57 units. After changing the injection sites to avoid the insulin
      derived amyloidosis, the blood glucose concentrations improved, and the mean
      daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The
      insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal
      sites (P = .030). CONCLUSIONS: Insulin-derived amyloidosis caused poor glycemic
      control and increased insulin dose requirements because of impairments in insulin
      absorption.

PMID- 24462810
TI  - Increased spinal cord movements in cervical spondylotic myelopathy.
AB  - BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) is a very useful diagnostic
      test for cervical spondylotic myelopathy (CSM) because it can identify
      degenerative changes within the spinal cord (SC), disclose the extent,
      localization, and the kind of SC compression, and help rule out other SC
      disorders. However, the relationships between changes in cerebrospinal fluid
      (CSF) flow, cord motion, the extent and severity of spinal canal stenosis, and
      the development of CSM symptoms are not well understood. PURPOSE: To evaluate if
      changes in the velocity of CSF and SC movements provide additional insight into
      the pathophysiological mechanisms underlying CSM beyond MRI observations of cord
      compression. STUDY DESIGN: Prospective radiologic study of recruited patients.
      PATIENT SAMPLE: Thirteen CSM subjects and 15 age and gender matched controls.
      OUTCOME MEASURES: Magnetic resonance imaging measures included CSF and SC
      movement. Cervical cord condition was assessed by the Japanese Orthopaedic
      Association (JOA) score, compression ratio (CR), and somatosensory evoked
      potentials (SSEPs) of the tibial and ulnar nerves. METHODS: Phase-contrast
      imaging at the level of stenosis for patients and at C5 for controls and T2
      weighted images were compared with clinical findings. RESULTS: Cerebrospinal
      fluid velocity was significantly reduced in CSM subjects as compared with
      controls and was related to cord CR. Changes in CSF velocity and cord compression
      were not correlated with clinical measures (JOA scores, SSEP) or the presence of
      T2 hyperintensities. Spinal cord movements, that is, cord displacement and
      velocity in the craniocaudal axis, were increased in CSM patients. Increased SC
      movements (ie, total cord displacement) both in the controls and CSM subjects
      were associated with altered spinal conduction as assessed by SSEP. CONCLUSIONS:
      This study revealed rather unexpected increased cord movements in the
      craniocaudal axis in CSM patients that may contribute to myelopathic
      deteriorations in combination with spinal canal compression. Understanding the
      relevance of cord movements with respect to supporting the clinical CSM diagnosis
      or disease monitoring requires further long-term follow-up studies.

PMID- 24462811
TI  - Increasing the specimen adequacy of transpedicular vertebral body biopsies. Role
      of intraoperative scrape cytology.
AB  - BACKGROUND CONTEXT: Obtaining adequate representative material has been a problem
      in transpedicular vertebral body biopsies resulting in inconclusive diagnosis and
      delayed management. By rapidly confirming the adequacy of the material
      intraoperatively, the rate of negative biopsies can be minimized. Present study
      evaluates the role of intraoperative cytology in increasing the diagnostic yield
      of vertebral biopsies. PURPOSE: To evaluate the role of intraoperative
      cytological confirmation in increasing the specimen adequacy of vertebral
      biopsies. STUDY DESIGN: A prospective cytological and histopathologic study.
      PATIENT SAMPLE: Thirty-nine patients undergoing transpedicular biopsy were
      included. OUTCOME MEASURES: Adequacy and accuracy along with sensitivity and
      specificity of transpedicular biopsies with and without adopting scrape
      cytological screening were analyzed. METHODS: After obtaining transpedicular
      specimens, they were initially screened by intraoperative cytology before
      submitting for histopathologic examination. Cytological smears were prepared by
      rapid hematoxylin and eosin technique. Additional specimens were obtained if
      cytology showed inadequate or inconclusive cells. RESULTS: Of 39 patients who
      underwent transpedicular biopsy, the intraoperative cytology confirmed 32 (82.1%)
      specimens as adequate, 5 (12.8%) inadequate, and 2 (5.1%) as inconclusive.
      Adequacy of biopsy specimens with intraoperative cytology was found to have a
      sensitivity of 96.9%, specificity of 100%, positive predictive value of 100%, and
      negative predictive value of 87.5%. If the intraoperative cytology was not
      adopted, six of 39 (15.4%) patients would have required repeat biopsy. Of the 47
      specimens from 39 lesions, 46 intraoperative cytological diagnoses correlated
      well with the histopathology, with an accuracy of 95.7%. The average time taken
      to report the adequacy was 8.9 +/- 1.7 minutes. CONCLUSIONS: Onsite
      intraoperative cytology is a rapid and an inexpensive technique to obtain
      accurate and adequate vertebral body tissue specimen with 100% diagnostic yield.
      The technique can be adopted easily into day-to-day practice and requires only
      few glass slides and regular reagents.

PMID- 24462812
TI  - Do stand-alone interbody spacers with integrated screws provide adequate
      segmental stability for multilevel cervical arthrodesis?
AB  - BACKGROUND CONTEXT: Some postoperative complications after anterior cervical
      fusions have been attributed to anterior cervical plate (ACP) profiles and the
      necessary wide operative exposure for their insertion. Consequently, low-profile
      stand-alone interbody spacers with integrated screws (SIS) have been developed.
      Although SIS constructs have demonstrated similar biomechanical stability to the
      ACP in single-level fusions, their role as a stand-alone device in multilevel
      reconstructions has not been thoroughly evaluated. PURPOSE: To evaluate the acute
      segmental stability afforded by an SIS device compared with the traditional ACP
      in the setting of a multilevel cervical arthrodesis. STUDY DESIGN: In vitro human
      cadaveric biomechanical analysis. METHODS: Thirteen human cadaveric cervical
      spines (C2-T1) were nondestructively tested with a custom 6 df spine simulator
      under axial rotation, flexion-extension, and lateral bending loading. After
      intact analysis, eight single-levels (C4-C5/C6-C7) from four specimens were
      instrumented and tested with ACP and SIS. Nine specimens were tested with C5-C7
      SIS, C5-C7 ACP, C4-C7 ACP, C4-C7 ACP+posterior fixation, C4-C7 SIS, and C4-C7
      SIS+posterior fixation. Testing order was randomized with each additional level
      instrumented. Full range of motion (ROM) data were obtained and analyzed by each
      loading modality, using mean comparisons with repeated measures analysis of
      variance. Paired t tests were used for post hoc analysis with Sidak correction
      for multiple comparisons. RESULTS: No significant difference in ROM was noted
      between the ACP and SIS for single-level fixation (p>.05). For multisegment
      reconstructions (two and three levels), the ACP proved superior to SIS and intact
      condition, with significantly lower ROM in all planes (p<.05). When either the
      three-level SIS or ACP constructs were supplemented with posterior lateral mass
      fixation, there was a greater than 80% reduction in ROM under all testing
      modalities (p<.05), with no significant difference between the ACP and SIS
      constructs (p>.05). CONCLUSIONS: The SIS device may be a reasonable option as a
      stand-alone device for single-level fixation. However, SIS devices should be used
      with careful consideration in the setting of multilevel cervical fusion. However,
      when supplemented with posterior fixation, SIS devices are a sound biomechanical
      alternative to ACP for multilevel fusion constructs.

PMID- 24462813
TI  - Differences in the surgical treatment of recurrent lumbar disc herniation among
      spine surgeons in the United States.
AB  - BACKGROUND CONTEXT: There are often multiple surgical treatment options for a
      spinal pathology. In addition, there is a lack of data that define differences in
      surgical treatment among surgeons in the United States. PURPOSE: To assess the
      surgical treatment patterns among neurologic and orthopedic spine surgeons in the
      United States for the treatment of one- and two-time recurrent lumbar disc
      herniation. STUDY DESIGN: Electronic survey. PATIENT SAMPLE: An electronic survey
      was delivered to 2,560 orthopedic and neurologic surgeons in the United States.
      OUTCOME MEASURES: The response data were analyzed to assess the differences among
      respondents over various demographic variables. The probability of disagreement
      is reported for various surgeon subgroups. METHODS: A survey of clinical and
      radiographic case scenarios that included a one- and two-time lumbar disc
      herniation was electronically delivered to 2,560 orthopedic and neurologic
      surgeons in the United States. The surgical treatment options were revision
      microdiscectomy, revision microdiscectomy with in situ fusion, revision
      microdiscectomy with posterolateral fusion using pedicle screws, revision
      microdiscectomy with posterior lumbar interbody fusion/transforaminal lumbar
      interbody fusion (PLIF/TLIF), anterior lumbar interbody fusion (ALIF) with
      percutaneous screws, ALIF with open posterior instrumentation, or none of these.
      Significance of p=.01 was used to account for multiple comparisons. RESULTS: Four
      hundred forty-five surgeons (18%) completed the survey. Surgeons in practice for
      15+ years were more likely to select revision microdiscectomy compared with
      surgeons with fewer years in practice who were more likely to select revision
      microdiscectomy with PLIF/TLIF (p<.001). Similarly, those surgeons performing
      200+ surgeries per year were more likely to select revision microdiscectomy with
      PLIF/TLIF than those performing fewer surgeries (p=.003). No significant
      differences were identified for region, specialty, fellowship training, or
      practice type. Overall, there was a 69% and 22% probability that two randomly
      selected spine surgeons would disagree on the surgical treatment of two- and one
      time recurrent disc herniations, respectively. This probability of disagreement
      was consistent over multiple variables including geographic, practice type,
      fellowship training, and annual case volume. CONCLUSIONS: Significant differences
      exist among US spine surgeons in the surgical treatment of recurrent lumbar disc
      herniations. It will become increasingly important to understand the underlying
      reasons for these differences and to define the most cost-effective surgical
      strategies for these common lumbar pathologies as the United States moves closer
      to a value-based health-care system.

PMID- 24462814
TI  - Biomechanical analysis of four- versus six-screw constructs for short-segment
      pedicle screw and rod instrumentation of unstable thoracolumbar fractures.
AB  - BACKGROUND CONTEXT: Conventionally, short-segment fusion involves instrumentation
      of one healthy vertebra above and below the injured vertebra, skipping the
      injured level. This short-segment construct places less surgical burden on the
      patient compared with long-segment constructs, but is less stable
      biomechanically, and thus has resulted in clinical failures. The addition of two
      screws placed in the fractured vertebral body represents an attempt to improve
      the construct stiffness without sacrificing the benefits of short-segment fusion.
      PURPOSE: To determine the biomechanical differences between four- and six-screw
      short-segment constructs for the operative management of an unstable L1 fracture.
      STUDY DESIGN: Biomechanical study of instrumentation in vertebral body cadaveric
      models simulating an L1 axial load injury pattern. METHODS: Thirteen intact
      spinal segments from T12 to L2 were prepared from fresh-frozen cadaver spines. An
      axial load fracture of at least 50% vertebral body height was produced at L1 and
      then instrumented with pedicle screws. Specimens were evaluated in terms of
      construct stiffness, motion, and rod strain. Two conditions were tested: a four
      screw construct with no screws at the L1 fractured body (4S) and a six-screw
      construct with screws at all levels (6S). The two groups were compared
      statistically by paired Student t test. RESULTS: The mean stiffness in flexion
      extension was increased 31% (p<.03) with the addition of the two pedicle screws
      in L1. Relative motion in terms of vertical and axial rotations was not
      significantly different between the two groups. The L1-L2 rod strain was
      significantly increased in the six-screw construct compared with the four-screw
      construct (p<.001). CONCLUSIONS: In a cadaveric L1 axial load fracture model, a
      six-screw construct with screws in the fractured level is more rigid than a four
      screw construct that skips the injured vertebral body.

PMID- 24462815
TI  - Fibromyalgia and cytokines.
AB  - Fibromyalgia is a common chronic pain syndrome characterized by widespread pains
      and characteristic somatic symptoms. Current evidence suggests that cytokines and
      especially chemokines may have a role in the pathogenesis of this syndrome.
      Cytokines are small soluble factors that work as immune system messengers. They
      can be classified as pro-inflammatory and anti-inflammatory cytokines. Chemokines
      are a special kind of pro-inflammatory cytokines that guide the movement of
      circulating mononuclear cells to the injured side. Some pro-inflammatory cytokine
      levels (i.e. IL-1RA, IL-6, and IL-8) and, recently, some chemokines' levels have
      been found to be increased in patients with fibromyalgia. Thus, herein we review
      the current knowledge regarding the role of cytokines in fibromyalgia patients
      and their possible clinical relevance. 

PMID- 24462816
TI  - Evolutionary implications of dipluran hexamerins.
AB  - Hexamerin, as a member of the highly conserved arthropod hemocyanin superfamily,
      has been shown to be a good marker for the phylogenetic study of insects.
      However, few studies have been conducted on hexamerins in basal hexapods. The
      first Diplura hexamerin CspHex1 was reported only recently (Pick and Burmester,
      2009). Remarkably, CspHex1 was suggested to have evolved from hexapod hemocyanin
      subunit type 2, which is very different from all insect hexamerins originated
      from hexapod hemocyanin subunit type 1. Does this finding suggest double or even
      multiple origins of hexamerins in Hexapoda? To find more evidence on the
      evolution of dipluran hexamerins, eight putative hexamerin gene sequences were
      obtained from three dipluran species, as were three hemocyanin genes from two
      collembolan species. Unexpectedly, after adding the new sequences into the
      phylogenetic analyses, all dipluran hexamerins including CspHex1 grouped together
      and as sister to the insect hexamerins, with high likelihood and Bayesian
      support. Our analysis supports a single origin of the hexamerins in Hexapoda, and
      suggests the close relationship between Diplura and Insecta. In addition, our
      study indicates that a relatively comprehensive taxa sampling is essential to
      solve some problems in phylogenetic reconstruction. 

PMID- 24462817
TI  - Boron nitride as desalting material in combination with phosphopeptide enrichment
      in shotgun proteomics.
AB  - Hydrophilic peptides in shotgun proteomics have been shown to be problematic in
      conventional chromatography. Typically, C18 solid phase extraction or peptide
      traps are used for desalting the sample prior to mass spectrometry analysis, but
      the capacity to retain hydrophilic peptides is not very high, causing a bias
      toward more hydrophobic peptides. This is particularly problematic in
      phosphoproteomic studies. We tested the compatibility of commercially available
      boron nitride as a novel material for peptide desalting. Boron nitride can be
      used to recover a wide range of peptides with different physicochemical
      properties comparable to combined C18 and graphite carbon material. 

PMID- 24462818
TI  - Nucleotide excision repair: why is it not used to predict response to platinum
      based chemotherapy?
AB  - Platinum based therapy is one of the most effectively used chemotherapeutic
      treatments for cancer. The mechanism of action of platinum compounds is to damage
      DNA and drive cells into apoptosis. The most commonly used platinum containing
      agents are cis-diammine-dichloroplatinum (II)], more commonly known as cisplatin,
      its analogue carboplatin, and oxaliplatin. Cisplatin is used to treat a wide
      variety of tumours such as ovarian, testicular, head and neck and non-small cell
      lung cancers (NSCLCs). In addition, it forms the basis of most combined treatment
      regimes. Despite this, cisplatin and its analogues are extremely toxic and
      although some patients benefit substantially from treatment, a large proportion
      suffer the toxic side effects without any therapeutic benefit. Nucleotide
      excision repair (NER) is a versatile DNA repair system that recognises DNA damage
      induced by platinum based therapy. For many years the components of the NER
      pathway have been studied to determine mRNA and protein expression levels in
      response or resistance to cisplatin in many forms of cancer; particularly
      testicular, ovarian and NSCLCs. Despite the consistent finding that over or under
      expression of subsets of NER proteins and mRNA highly correlate with response to
      cisplatin, the translation of these findings into the clinical setting has not
      been forthcoming. This review summarises the results of previous investigations
      into NER in cisplatin response and clinical trials where the expression of NER
      proteins were compared to the response to platinum therapies in treatment. 

PMID- 24462819
TI  - Cancer statistics: current diagnosis and treatment of pancreatic cancer in
      Shanghai, China.
AB  - A multi-center population-based study in Shanghai, China was performed to explore
      the implications for the management of pancreatic cancer by comparing diagnosis
      and survival rates. Novel imaging modalities including MRI (13.9%), PET/CT
      (1.8%), and EUS (5.6%) were not widely used in our population. Only 39.7% of
      cases were histologically verified (surgery with histologic diagnosis 31.0%,
      cytological diagnosis 8.7%, surgery without histologic diagnosis 12.1%, and
      clinical diagnosis 48.2%). Overall, 30.0% of patients underwent curative-intent
      operation, and only 9.8% of patients received comprehensive treatment. The
      prognosis of pancreatic cancer patients was significantly better for patients who
      were treated in high-volume centers than in low-volume centers. We propose that
      more effort should be put on novel diagnostic modalities, histological
      confirmation, and comprehensive treatment in China. Multidisciplinary teams
      specialized in pancreatic cancer therapy in high-volume centers are urgently
      needed. 

PMID- 24462820
TI  - Blood autoantibodies against tumor-associated antigens as biomarkers in early
      detection of colorectal cancer.
AB  - Multiple studies have shown that cancer patients produce detectable
      autoantibodies against certain tumor-associated antigens, which might be
      promising blood biomarkers for early detection of colorectal cancer (CRC). We
      aimed to provide an overview of published studies on blood autoantibody markers
      for early detection of CRC and to summarize their diagnostic performance. A
      systematic literature search was performed in PubMed, ISI Web of Knowledge and
      EMBASE to find relevant studies published until 23 July 2013. Relevant
      information, such as study population characteristics, autoantibodies studied,
      analytical methods and diagnostic performance characteristics was independently
      extracted by two reviewers. Overall, 67 studies evaluating 109 autoantibody
      markers were included. Most individual markers showed low sensitivity (below 25%)
      for detecting CRC, along with high specificity close to 100%. Occasionally
      reported higher sensitivities for specific antibodies are yet to be replicated in
      independent studies. Generally, more promising results were seen for combinations
      of multiple autoantibody markers. But again, these promising results are yet to
      be replicated in other samples. In conclusion, autoantibody signatures may become
      a promising approach to noninvasive CRC screening. Optimized marker panels are
      yet to be developed, and promising results require validation in large screening
      populations. 

PMID- 24462821
TI  - Inhibition of p53 increases chemosensitivity to 5-FU in nutrient-deprived
      hepatocarcinoma cells by suppressing autophagy.
AB  - Activation of p53 can induce apoptosis, cell cycle arrest, and cell senescence,
      although some evidence has suggested that p53 could promote cell survival.
      However, whether p53 plays a positive role in cancer cell survival to
      chemotherapy remains unknown. In this study, we show that inhibition of p53
      enhanced apoptosis and increased chemosensitivity to 5-fluorouracil (5-FU) in
      nutrient-deprived hepatocarcinoma cells (HCC). Meanwhile, nutrient-deprivation
      induced autophagy was inhibited by pifithrin-alpha or small interfering RNA
      targeting p53. The expression of p53 was not increased when HCC were incubated
      under nutrient-deprived conditions. This indicates that the basal level of p53 is
      important to autophagy activation in nutrient-deprived HCC cells. Furthermore,
      combining p53 inhibition and nutrient deprivation or 5-FU treatment resulted in a
      marked increase in reactive oxygen species generation and mitochondrial damage.
      Antioxidants reduced nutrient deprivation or 5-FU-induced cell death of HCC after
      p53 inhibition. Our results suggest that p53 contributes to cell survival and
      chemoresistance in HCC under nutrient-deprived conditions by modulating autophagy
      activation. 

PMID- 24462822
TI  - Fulvestrant, a selective estrogen receptor down-regulator, sensitizes estrogen
      receptor negative breast tumors to chemotherapy.
AB  - Drug resistance frequently results in poor prognosis and high 5-year recurrence
      rate in estrogen receptor-negative (ER-) breast cancer patients. Herein, we
      examined the reversal effects of fulvestrant on multidrug resistance (MDR) in ER-
      breast cancer cells. Co-administration of fulvestrant significantly sensitized ER
      MDR tumors to paclitaxel both in vitro and in vivo. Further analyses indicated
      that fulvestrant did not affect P-gp expression, but could inhibit P-gp function
      and subsequently reverse P-gp mediated drug resistance in ER- breast cancer
      cells. These results showed that combination of fulvestrant and chemotherapeutic
      agents might provide an effective treatment for ER- MDR breast cancers. 

PMID- 24462823
TI  - Metformin: a metabolic disruptor and anti-diabetic drug to target human leukemia.
AB  - There is a global and urgent need for expanding our current therapeutical arsenal
      against leukemia in order to improve their actual cure rates and fight relapse.
      Targeting the reprogrammed, altered cancer metabolism is an emerging strategy
      which should profoundly affect cancer cells in their intimate and irrepressible
      needs and addictions for nutrients uptake and incorporation into the biomass
      during malignant proliferation. We present here how metformin, an anti-diabetic
      drug that has attracted a strong interest for its recently discovered anti-cancer
      properties, can be envisioned as a new adjuvant approach to treat leukemia.
      Metformin may have a double-edged sword effect (i) by acting on the organism to
      decrease hyperglycaemia and hyperinsulinemia in diabetic patients and (ii) at the
      cellular level, by inhibiting the mTORC1-cancer supporting pathway through AMPK
      dependent and independent mechanisms. 

PMID- 24462824
TI  - Nanosecond pulsed electric field (nsPEF) treatment for hepatocellular carcinoma:
      a novel locoregional ablation decreasing lung metastasis.
AB  - Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Nanosecond
      pulsed electric field (nsPEF) is a new technology destroying tumor cells with a
      non-thermal high voltage electric field using ultra-short pulses. The study's aim
      was to evaluate the ablation efficacy of nsPEFs with human HCC cell lines and a
      highly metastatic potential HCC xenograft model on BALB/c nude mice. The in vivo
      study showed nsPEFs induced HCC cell death in a dose dependent manner. On the
      high metastatic hepatocellular carcinoma cell line (HCCLM3) xenograft mice model,
      tumor growth was inhibited significantly in nsPEF-treated- groups (single dose
      and multi-fractionated dose). Besides a local effect, the nsPEF treatment reduced
      pulmonary metastases. The nsPEFs also enhanced HCC cell phagocytosis by human
      macrophage cell (THP1) in vitro. The nsPEF is efficient in controlling HCC
      progression and reducing its metastasis. NsPEF treatment may elicit a host immune
      response against tumor cells. This study suggests nsPEF therapy could be used as
      a potential locoregional therapy for hepatocellular carcinoma. 

PMID- 24462825
TI  - Detection and partial characterization of a bacteriocin-like substance produced
      by Lactobacillus fermentum CS57 isolated from human vaginal secretions.
AB  - Lactobacilli (150) from human vaginal secretions were tested for the production
      of antimicrobial substances which can provide a physiological defense against the
      pathogenic microorganisms in the vaginal area. Sixteen of the isolates (10.6%)
      showed antibacterial activity against one or several closely related
      microorganisms used as indicators. Lactobacillus fermentum CS57 was the best
      producer and secretes a bacteriocin-like substance (BLS) with antagonistic
      activity against Streptococcus agalactiae and Candida albicans. The compound was
      susceptible to the proteolytic enzymes and was heat labile. The mode of action
      was identified as bactericidal. The crude activity of the L. fermentum CS57 BLS
      was linked to a substance with a molecular weight larger than 30 kDa. Plasmid
      analysis of L. fermentum CS57 revealed the presence of a plasmid band with
      molecular weight of 54.7 kb. All L. fermentum CS57 non-producer variants (BLS-)
      obtained by curing experiments, showed loss of plasmid band and were susceptible
      to the BLS of the original strain. Therefore antimicrobial activity and immunity
      production seem to be linked to genes located on that same plasmid. Taking into
      account our results, L. fermentum CS57 could be considered a candidate for
      potential use as probiotic for the prophylaxis of vaginal human infections. 

PMID- 24462826
TI  - A reply to correspondents to "Atmospheric pressure and infra-renal abdominal
      aortic aneurysm rupture: a single observational study and a comprehensive review
      of literature".

PMID- 24462827
TI  - One-step electrodeposition of graphene loaded nickel oxides nanoparticles for
      acetaminophen detection.
AB  - An electrochemical sensor of acetaminophen (AP) based on electrochemically
      reduced graphene (ERG) loaded nickel oxides (Ni2O3-NiO) nanoparticles coated onto
      glassy carbon electrode (ERG/Ni2O3-NiO/GCE) was prepared by a one-step
      electrodeposition process. The as-prepared electrode was characterized by
      scanning electron microscopy, X-ray photoelectron spectroscopy and Raman
      spectroscopy. The electrocatalytic properties of ERG/Ni2O3-NiO modified glassy
      carbon electrode toward the oxidation of acetaminophen were analyzed via cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV). The electrodes of
      Ni2O3-NiO/GCE, ERG/GCE, and Ni2O3-NiO deposited ERG/GCE were fabricated for the
      comparison and the catalytic mechanism understanding. The studies showed that the
      one-step prepared ERG/Ni2O3-NiO/GCE displayed the highest electro-catalytic
      activity, attributing to the synergetic effect derived from the unique composite
      structure and physical properties of nickel oxides nanoparticles and graphene.
      The low detection limit of 0.02 MUM (S/N=3) with the wide linear detection range
      from 0.04 MUM to 100 MUM (R=0.998) was obtained. The resulting sensor was
      successfully used to detect acetaminophen in commercial pharmaceutical tablets
      and urine samples.

PMID- 24462828
TI  - Robust ZnO nanoparticle embedded memory device using vancomycin conjugate and its
      biorecognition for electrical charging node.
AB  - Conjugation of antibiotic vancomycin (VAN) on nanoparticles (NPs) has recently
      initiated novel works in the nanobiotechnology field. In this study, a
      bioelectronic structure using VAN conjugated zinc oxide (ZnO) NPs as charge
      storing elements on metal-pentacene-insulator-silicon (MPIS) device is
      demonstrated. Highly specific molecular recognition between the VAN and membrane
      protein unit mimicked from VAN-resistant bacteria is employed as the formation
      mechanism of self-assembly monolayers (SAMs) of ZnO NPs. The insulator surface is
      modified with the VAN cognate peptide of L-Ala-D-Glu-L-Lys-D-Ala-D-Ala by
      chemical activator coupling. Hysteretic behaviors in capacitance versus voltage
      (C-V) curves are obtained for the charged ZnO NPs exhibiting flatband voltage
      shifts, which demonstrate the charge storage on the VAN conjugated ZnO NPs. The
      potential perspective of this study will be a tangible progress of biomolecular
      electronics implemented by the interface between biomolecules and electronics.

PMID- 24462829
TI  - A dual-mode nanosensor based on carbon quantum dots and gold nanoparticles for
      discriminative detection of glutathione in human plasma.
AB  - Glutathione (GSH) plays key roles in biological systems and serves many cellular
      functions. Since biothiols all incorporate thiol, carboxylic and amino groups,
      discriminative detection of GSH over cysteine (Cys) and homocysteine (Hcy) is
      still challenging. We herein report a dual-mode nanosensor with both colorimetric
      and fluorometric readout based on carbon quantum dots and gold nanoparticles for
      discriminative detection of GSH over Cys/Hcy. The proposed sensing system
      consists of AuNPs and fluorescent carbon quantum dots (CQDs), where CQDs function
      as fluorometric reporter, and AuNPs serve a dual function as colorimetric
      reporter and fluorescence quencher. The mechanism of the nanosensor is based on
      two distance-dependent phenomenons, color change of AuNPs and FRET. Through
      controlling the surface properties of as-prepared nanoparticles, the addition of
      CQDs into AuNPs colloid solution might induce the aggregation of AuNPs and CQDs,
      leading to AuNPs color changing from red to blue and CQDs fluorescence quench.
      However, the presence of GSH can protect AuNPs from being aggregated and enlarge
      the inter-particle distance, which subsequently produces color change and
      fluorescent signal recovery. The nanosensor described in this report reflects on
      its simplicity and flexibility, where no further surface functionalization is
      required for the as-prepared nanoparticles, leading to less laborious and more
      cost-effective synthesis. The proposed dual-mode nanosensor demonstrated highly
      selectivity toward GSH, and allows the detection of GSH as low as 50 nM. More
      importantly, the nanosensor could not only function in aqueous solution for GSH
      detection with high sensitivity but also exhibit sensitive responses toward GSH
      in complicated biological environments, demonstrating its potential in
      bioanalysis and biodection, which might be significant in disease diagnosis in
      the future.

PMID- 24462830
TI  - Silver nanoparticles induced changes in the expression of NF-kappaB related genes
      are cell type specific and related to the basal activity of NF-kappaB.
AB  - Silver nanoparticles (AgNPs) are widely used in industry and medicine but the
      recent evidence for their cytotoxicity rise a concern about the safety of their
      use. We have previously shown that human A549 cells are resistant to AgNPs
      cytotoxicity, as compared with similarly treated HepG2 cells. In order to check
      for the role of the NF-kappaB signaling pathway in response of A549 and HepG2
      cell lines to the treatment with 20 nm and 200 nm AgNps, we analyzed the
      expression of 84 key genes related to the functionality of the NF-kappaB
      signaling pathway. We observed considerable alternations in gene expression in
      HepG2 cells treated with 20 nm AgNPs, and minor changes when exposed to 200 nm
      AgNPs. Surprisingly, no changes in gene expression were observed in A549 cells
      treated with both size AgNPs. Using the NF-kappaB luciferase reporter system, we
      further tested the basal activity and inducibility of the NF-kappaB pathway in
      both cell lines and found that the inducibility of NF-kappaB signaling in A549
      cells is approximately 5 times lower than this of HepG2 cells, but the basal
      activity is approximately 3.5 times higher. In accordance, the NF-kappaB
      activation after AgNPs treatment was observed in HepG2 but not in A549.
      Altogether indicate that NF-kB mediated cellular response to AgNPs is cell type
      specific and related to the basal activity of NF-kappaB.

PMID- 24462832
TI  - Validation of interleukin 28B genotyping assay for clinical use.
AB  - OBJECTIVES: The favorable CC genotype at rs12979860 upstream of the interleukin
      (IL)-28B gene is correlated with a greater post-treatment sustained virologic
      response rate in chronic hepatitis C infected patients. We report on our
      validation of a clinical genotyping assay for rs12979860 polymorphisms in the
      IL28B locus. DESIGN AND METHODS: The rs12979860 genotype was determined using a
      TaqMan(r) Real-Time PCR allelic discrimination assay with primers and probes
      specific for the C and T alleles on the Applied Biosystems 7500 Fast Real-Time
      PCR System. RESULTS: The rs12979860 genotype determined by our assay was
      concordant with the genotypes obtained from a reference laboratory. The allelic
      frequency was similar to that reported in the HapMap project (rs12979860 C=0.65,
      T=0.35) and did not deviate from Hardy-Weinberg equilibrium. CONCLUSION: Clinical
      availability of this assay in conjunction with other factors will allow the
      prediction of the individual patient's response to therapy.

PMID- 24462831
TI  - BDNF secretion by human pulmonary artery endothelial cells in response to
      hypoxia.
AB  - Within human pulmonary artery, neurotrophin growth factors [NTs; e.g. brain
      derived neurotrophic factor (BDNF)] and their high-affinity receptors
      (tropomyosin-related kinase; Trk) and low-affinity receptors p75 neurotrophin
      receptor (p75NTR) have been reported, but their functional role is incompletely
      understood. We tested the hypothesis that BDNF is produced by human pulmonary
      artery endothelial cells (PAECs). In the context of hypoxia as a risk factor for
      pulmonary hypertension, we examined the effect of hypoxia on BDNF secretion and
      consequent autocrine effects on pulmonary endothelium. Initial ELISA analysis of
      circulating BDNF in 30 healthy human volunteers showed that 72 h exposure to high
      altitude (~11,000 ft, alveolar PO2 = 100 mmHg) results in higher BDNF compared to
      samples taken at sea level. Separately, in human PAECs exposed for 24h to
      normoxia vs. hypoxia (1-3% O2), ELISA of extracellular media showed increased
      BDNF levels. Furthermore, quantitative PCR of PAECs showed 3-fold enhancement of
      BDNF gene transcription with hypoxia. In PAECs, BDNF induced NO production
      (measured using an NO-sensitive fluorescent dye DAF2-DA) that was significantly
      higher under hypoxic conditions, an effect also noted with the TrkB agonist 7,8
      DHF. Importantly, hypoxia-induced NO was blunted by neutralization of secreted
      BDNF using the chimeric TrkB-Fc. Both hypoxia and BDNF increased iNOS (but not
      eNOS) mRNA expression. In accordance, BDNF enhancement of NO in hypoxia was not
      blunted by 50 nM L-NAME (eNOS inhibition) but substantially lower with 100 MUM L
      NAME (eNOS and iNOS inhibition). Hypoxia and BDNF also induced expression of
      hypoxia inducible factor 1 alpha (HIF-1alpha), a subunit of the transcription
      factor HIF-1, and pharmacological inhibition of HIF-1 diminished hypoxia effects
      on BDNF expression and secretion, and NO production. These results indicate that
      human PAECs express and secrete BDNF in response to hypoxia via a HIF-1-regulated
      pathway.

PMID- 24462833
TI  - Government and voluntary sector differences in organizational capacity to do and
      use evaluation.
AB  - Research on evaluation capacity is limited although a recent survey article on
      integrating evaluation into the organizational culture (Cousins, Goh, Clark, &
      Lee, 2004) revealed that interest in the topic is increasing. While knowledge
      about building the capacity to do evaluation has developed considerably, less is
      understood about building the organizational capacity to use evaluation. This
      article reports on the results of a pan-Canadian survey of evaluators working in
      organizations (internal evaluators or organization members with evaluation
      responsibility) conducted in 2007. Reliability across all constructs was high.
      Responses from government evaluators (N=160) were compared to responses from
      evaluators who work in the voluntary sector (N=89). The former were found to self
      identify more highly as 'evaluators' (specialists) whereas the latter tended to
      identify as 'managers' (non-specialists). As a result, government evaluators had
      significantly higher self-reported levels of evaluation knowledge (both theory
      and practice); and they spent more time performing evaluation functions. However,
      irrespective of role, voluntary sector respondents rated their organizations more
      favorably than did their government sector counterparts with respect to the
      antecedents or conditions supporting evaluation capacity, and the capacity to use
      evaluation. Results are discussed in terms of their implications for evaluation
      practice and ongoing research. 

PMID- 24462834
TI  - Complement system in zebrafish.
AB  - Zebrafish is recently emerging as a model species for the study of immunology and
      human diseases. Complement system is the humoral backbone of the innate immune
      defense, and our knowledge as such in zebrafish has dramatically increased in the
      recent years. This review summarizes the current research progress of zebrafish
      complement system. The global searching for complement components in genome
      database, together with published data, has unveiled the existence of all the
      orthologues of mammalian complement components identified thus far, including the
      complement regulatory proteins and complement receptors, in zebrafish.
      Interestingly, zebrafish complement components also display some distinctive
      features, such as prominent levels of extrahepatic expression and isotypic
      diversity of the complement components. Future studies should focus on the
      following issues that would be of special importance for understanding the
      physiological role of complement components in zebrafish: conclusive
      identification of complement genes, especially those with isotypic diversity;
      analysis and elucidation of function and mechanism of complement components;
      modulation of innate and adaptive immune response by complement system; and
      unconventional roles of complement-triggered pathways. 

PMID- 24462835
TI  - The essential roles of core binding factors CfRunt and CfCBFbeta in hemocyte
      production of scallop Chlamys farreri.
AB  - Core binding factor (CBF) is a family of heterodimeric transcription factors
      composed of a DNA-binding CBFalpha subunit and a non-DNA-binding CBFbeta subunit,
      which plays critical roles in regulating hematopoiesis, osteogenesis and
      neurogenesis. In the present study, two genes encoding Runt (designed as CfRunt)
      and CBFbeta (designed as CfCBFbeta) were cloned and characterized from scallop
      Chlamys farreri. The full-length cDNA of CfRunt and CfCBFbeta consists of 2128 bp
      and 1729 bp encoding a predicted polypeptide of 530 and 183 amino acids with a
      conserved Runt domain and CBFbeta domain, respectively. Electrophoretic mobility
      shift assay demonstrated that the recombinant CfRunt protein (rCfRunt) exhibited
      solid ability to bind specific DNA, whereas rCfCBFbeta could remarkably increase
      the DNA-binding affinity of rCfRunt. The mRNA transcripts of CfRunt and CfCBFbeta
      could be detected in all tested tissues, especially in hemocytes, heart,
      hepatopancreas or muscle. After bacterial challenge, the circulating total
      hemocyte count (THC) of scallop reduced to the lowest level at 6h (P<0.05), and
      then it recovered gradually to the control level at 48-96 h, while the mRNA
      expressions of CfRunt and CfCBFbeta were significant up-regulated between 6 and
      48 h (P<0.05). After CfRunt gene was silenced by RNA interference, the hemocyte
      renewal rate and circulating THC both decreased significantly (P<0.05). However,
      following the RNA interference of CfRunt, the mRNA expression of CfRunt was
      significantly induced (P<0.05) and the attenuated hemocyte renewal rate and
      circulating THC could be repaired partially by LPS stimulation in the CfRunt
      silenced scallops. The results collectively indicated that CfRunt and CfCBFbeta,
      as conserved transcription factors, played essential roles in regulating hemocyte
      production of scallop.

PMID- 24462836
TI  - Cloning and characterization of two different ficolins from the giant freshwater
      prawn Macrobrachium rosenbergii.
AB  - Ficolins, a kind of lectin containing collagen-like and fibrinogen-related
      domains (FReDs, also known as FBG or FREP), are involved in the first line of
      host defense against pathogens. In this study, two ficolins, namely, MrFico1 and
      MrFico2, from the giant freshwater prawn Macrobrachium rosenbergii were
      identified. In contrast to other ficolins, these two ficolins have no collagen
      like domain, but such ficolins contain a coiled region and a FReD domain.
      Phylogenetic analysis showed that MrFico1 and MrFico2, together with two ficolin
      like proteins from Pacifastacus leniusculus, belonged to one group. Quantitative
      RT-PCR (qRT-PCR) showed that both MrFico1 and MrFico2 were expressed in
      hepatopancreas, stomach and intestine, with the highest expression in stomach for
      MrFico1, compared to the highest expression in hepatopancreas for MrFico2. qRT
      PCR analysis also showed that MrFico1 was obviously upregulated upon Vibrio
      anguillarium challenge, while MrFico2 was upregulated after challenged by V.
      anguillarium or white spot syndrome virus. Bacterium-binding experiment showed
      that MrFico1 and MrFico2 could bind to different microbes, and sugar-binding
      assay revealed that these two ficolins could also bind to lipopolysaccharide and
      peptidoglycan, the glycoconjugates of bacteria surface. Moreover, these two
      ficolins could agglutinate bacteria in a calcium-dependent manner, and the
      results of bacteria clearance experiment showed that both ficolins could
      facilitate the clearance of injected bacteria in the prawn. Our results suggested
      that MrFico1 and MrFico2 may function as pattern-recognition receptors in the
      immune system of M. rosenbergii.

PMID- 24462837
TI  - Vesico-appendiceal fistula revealing pseudomyxoma peritonei.
AB  - We report a case of grade III pseudomyxoma peritonei revealed by mucusuria and
      abdominal mass. These symptoms are unusual; the most frequent clinical
      presentation is acute appendicitis or progressively increasing abdominal
      diameter. 

PMID- 24462838
TI  - Extreme emergency splenectomy.

PMID- 24462840
TI  - A review of experimental infections with bluetongue virus in the mammalian host.
AB  - Experimental infection studies with bluetongue virus (BTV) in the mammalian host
      have a history that stretches back to the late 18th century. Studies in a wide
      range of ruminant and camelid species as well as mice have been instrumental in
      understanding BTV transmission, bluetongue (BT) pathogenicity/pathogenesis, viral
      virulence, the induced immune response, as well as reproductive failures
      associated with BTV infection. These studies have in many cases been complemented
      by in vitro studies with BTV in different cell types in tissue culture. Together
      these studies have formed the basis for the understanding of BTV-host interaction
      and have contributed to the design of successful control strategies, including
      the development of effective vaccines. This review describes some of the
      fundamental and contemporary infection studies that have been conducted with BTV
      in the mammalian host and provides an overview of the principal animal welfare
      issues that should be considered when designing experimental infection studies
      with BTV in in vivo infection models. Examples are provided from the authors' own
      laboratory where the three Rs (replacement, reduction and refinement) have been
      implemented in the design of experimental infection studies with BTV in mice and
      goats. The use of the ARRIVE guidelines for the reporting of data from animal
      infection studies is emphasized. 

PMID- 24462839
TI  - Incidence, prevalence, costs, and impact on disability of common conditions
      requiring rehabilitation in the United States: stroke, spinal cord injury,
      traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis,
      limb loss, and back pain.
AB  - OBJECTIVE: To determine the relative incidence, prevalence, costs, and impact on
      disability of 8 common conditions treated by rehabilitation professionals. DATA
      SOURCES: Comprehensive bibliographic searches using MEDLINE, Google Scholar, and
      UpToDate, (June, 2013). DATA EXTRACTION: Two review authors independently
      screened the search results and performed data extraction. Eighty-two articles
      were identified that had relevant data on the following conditions: Stroke,
      Spinal Cord Injury, Traumatic Brain Injury, Multiple Sclerosis, Osteoarthritis,
      Rheumatoid Arthritis, Limb Loss, and Back Pain. DATA SYNTHESIS: Back pain and
      arthritis (osteoarthritis, rheumatoid arthritis) are the most common and costly
      conditions we analyzed, affecting more than 100 million individuals and costing
      greater than $200 billion per year. Traumatic brain injury, while less common
      than arthritis and back pain, carries enormous per capita direct and indirect
      costs, mostly because of the young age of those involved and the severe
      disability that it may cause. Finally, stroke, which is often listed as the most
      common cause of disability, is likely second to both arthritis and back pain in
      its impact on functional limitations. CONCLUSIONS: Of the common rehabilitation
      diagnoses we studied, musculoskeletal conditions such as back pain and arthritis
      likely have the most impact on the health care system because of their high
      prevalence and impact on disability.

PMID- 24462841
TI  - Facilitation of the swallowing reflex with bilateral afferent input from the
      superior laryngeal nerve.
AB  - To determine the cooperative effect of laryngeal afferent signals on the
      swallowing reflex, we examined whether afferent signals originating from the left
      and right superior laryngeal nerve (SLN) modulates elicitation of the swallowing
      reflex in urethane-anesthetized rats. Mylohyoid electromyographic activity was
      recorded to quantify the swallowing reflex. The onset latency of the swallowing
      reflex and the time intervals between successive swallows were used to quantify
      and compare the effects of unilateral and bilateral electrical stimulations of
      the SLN. The mean latency of the first swallow and the mean time interval between
      swallows evoked with low frequency stimulation were both significantly different
      between unilateral and bilateral stimulations of the SLN. These findings suggest
      that facilitatory effect of afferent signals originating from the SLN bilaterally
      increase the motoneuronal activity in the medullary swallowing center and enhance
      the swallowing reflex. 

PMID- 24462842
TI  - Epidermal growth factor increases the expression of Nestin in rat reactive
      astrocytes through the Ras-Raf-ERK pathway.
AB  - Astrocytes undergo de-differentiation and become activated during a response to
      injury. Several studies have found that reactive astrocytes re-express markers,
      such as Nestin, which are normally expressed in neural stem cells. It was
      recently shown that the epidermal growth factor receptor (EGFR) is up-regulated
      in astrocytes after injury and promotes reactive astrocyte transformation.
      However, the signaling pathways involved in this process have not been
      elucidated. In the present study, we showed that Nestin was strongly expressed in
      reactive astrocytes. Furthermore, as shown by immunoblot analyses, epidermal
      growth factor (EGF) regulated Nestin expression through EGFR activation.
      Inhibition of the PLCgamma, PI3K, ERK, p38, and JNK pathways did not affect
      Nestin expression in reactive astrocytes. However, treatment with a Raf-1
      inhibitor inhibited Nestin expression in a concentration-dependent manner. Taken
      together, the signaling analyses revealed that EGF induced and regulated Nestin
      expression through activation of the Ras-Raf--ERK signaling pathway. This is the
      first study to show that Nestin expression is regulated by an extracellular
      signaling molecule in reactive astrocytes. 

PMID- 24462843
TI  - Development of a cost-effective assay for genotyping of HIV-1 non-B subtype for
      drug resistance.
AB  - Highly Active Antiretroviral Therapy (HAART) is the most effective way to control
      HIV-1 replication in infected patients. Prior to the start of therapy, genotyping
      of HIV-1 for mutations that confer resistance to potential drug candidates is
      crucial for it allows formulating an effective regimen. Ineffective drugs are
      excluded and potentially effective ones are included. A number of diagnostic kits
      are commercially available for this purpose but are tailored for HIV-1 subtype-B,
      a strain chiefly found in AIDS patients of Europe and America. However, AIDS
      patients of South-East Asia including Thailand are predominant infected with HIV
      1 subtype non-B. In this study, an inexpensive assay was developed that genotypes
      HIV-1 non-B for drug resistance and tested it on 99 Thai AIDS patients. Results
      showed that 98 were infected with HIV-1 subtype non-B (or CRF01_AE) and one with
      subtype-B. Within the HIV-1 polymerase (pol), reverse transcriptase (RT) gene,
      the assay identified 18 codon mutations associated with resistance to
      Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) and 17 Non
      Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). Employing a commercially
      available kit, parallel genotyping of patient samples confirmed results providing
      validation of the assay. This method approximately costs 100 US dollars compared
      to $300 for a commercially available test. In Thailand, the burden of cost for
      treating HIV-infections is high not only for the average citizen but the
      country's health care systems. Therefore the low cost and yet effective
      genotyping test for HIV-1 subtype non-B is a practical and viable solution to
      expensive genotyping platforms. 

PMID- 24462844
TI  - Comparison of nucleic acid extraction and reverse transcription-qPCR approaches
      for detection of GI and GII noroviruses in drinking water.
AB  - The objective of this study was to compare three nucleic acid extraction and
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR) approaches
      for norovirus (NoV) detection in drinking water with respect to performance,
      costs, and analysis time. The approaches evaluated were: (A) an approach that
      utilizes the QIAamp DNA Blood Mini Kit and multiplex primers and probes for
      detection; (B) a procedure which includes the NucliSENS Magnetic Extraction Kit
      and other components of a proposed European Union standard method for NoV
      detection in foods; and (C) a commercialized assay which uses NucliSENS
      extraction and Cepheid SmartCycler(r) technologies. Each approach was evaluated
      by most probable number (MPN) analysis for detection of GI.1 and GII.4 NoVs from
      human stool. Furthermore, recoveries of spiked primary effluent in tap water
      concentrates were compared for each approach. Few significant differences were
      observed between approaches with regard to performance. However, Approach C was
      the most time consuming and expensive to perform. This research presents a case
      study of how molecular-based approaches for detection of NoVs can be compared and
      how various factors may play a role in which approach laboratories choose to
      employ. 

PMID- 24462845
TI  - Development of an assay to differentiate between virulent and vaccine strains of
      lumpy skin disease virus (LSDV).
AB  - Lumpy skin disease (LSD) was and still is a constant threat to the State of
      Israel, since the first outbreaks in 1989 and in 2006-2007. Recently, another
      massive outbreak occurred, at the beginning of July 2012, in the northern part of
      Israel. An intensive vaccination campaign with a sheeppox-based vaccine was
      initiated, in addition to culling symptomatic animals in the dairy herds. In
      spite of this, there was a need to apply extra efforts to completely contain and
      control the spread of the disease by introducing for the first time in Israel a
      vaccine based on the Neethling vaccine virus strain. However, in case of
      appearance of LSD symptoms it was essential to be able to distinguish between
      cattle-carried virulent strain and the vaccine strain. This paper describes the
      development and utilization of a molecular assay that can differentiate between
      the virulent isolates from the vaccine strain. The system is based on 3 different
      tests; it was found that the vaccine strain carries 27 bases less than the
      virulent virus in the extracellular enveloped virions (EEV) gene. A temperature
      gradient PCRs were done using primers which are identical to the vaccine strain
      but differ at the 3' end nucleotides to the virulent virus. PCR-RFLP was carried
      out on the presence of an MboI site unique to the vaccine strain. Thus, all three
      tests presented here are able to differentiate specifically between the two viral
      appearances. 

PMID- 24462846
TI  - Evaluation of the thermal stability of a novel strain of live-attenuated mumps
      vaccine (RS-12 strain) lyophilized in different stabilizers.
AB  - The stability of live-attenuated viral vaccines is important for immunization
      efficacy. Here, the thermostabilities of lyophilized live-attenuated mumps
      vaccine formulations in two different stabilizers, a trehalose dihydrate-based
      stabilizer and a stabilizer containing sucrose, human serum albumin and sorbitol
      were investigated using accelerated stability tests at 4 degrees C, 25 degrees C
      and 37 degrees C at time points between 4h (every 4h for the first 24h) and 1
      week. Even under the harshest storage conditions of 37 degrees C for 1 week, the
      50% cell culture infective dose (CCID50) determined from titrations in Vero cells
      dropped by less than 10-fold using each stabilizer formulation and thus complied
      with the World Health Organization's requirements for the potency of live
      attenuated mumps vaccines. However, as the half-life of the RS-12 strain mumps
      virus infectivity was lengthened substantially at elevated temperatures using the
      trehalose dihydrate (TD)-based stabilizer, this stabilizer is recommended for
      vaccine use. 

PMID- 24462847
TI  - Antifungal activity of oligochitosans (short chain chitosans) against some
      Candida species and clinical isolates of Candida albicans: molecular weight
      activity relationship.
AB  - A series of oligochitosans (short chain chitosans) prepared by acidic hydrolysis
      of chitosan and characterized by their molecular weight, polydispersity and
      degree of deacetylation were used to determine their anticandidal activities.
      This study has demonstrated that oligochitosans show a high fungistatic activity
      (MIC 8-512 MUg/ml) against Candida species and clinical isolates of Candida
      albicans, which are resistant to a series of classic antibiotics. Flow cytometry
      analysis showed that oligochitosan possessed a high fungicidal activity as well.
      For the first time it was shown that even sub-MIC oligochitosan concentration
      suppressed the formation of C. albicans hyphal structures, cause severe cell wall
      alterations, and altered internal cell structure. These results indicate that
      oligochitosan should be considered as a possible alternative/additive to known
      anti-yeast agents in pharmaceutical compositions.

PMID- 24462848
TI  - Inhibition of human thymidine phosphorylase by conformationally constrained
      pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres.
AB  - A series of conformationally constrained uridine-based nucleoside phosphonic
      acids containing annealed 1,3-dioxolane and 1,4-dioxane rings and their "open
      structure" isosteres were synthesized and evaluated as potential multisubstrate
      like inhibitors of the human recombinant thymidine phosphorylase (TP, EC 2.4.2.4)
      and TP obtained from peripheral blood mononuclear cells (PBMC). From a large set
      of tested nucleoside phosphonic acids, several potent compounds were identified
      that exhibited Ki values in the range of 0.048-1 MUM. The inhibition potency of
      the studied compounds strongly depended on the degree of conformational
      flexibility of the phosphonate moiety, the stereochemical arrangement of the
      sugar-phosphonate component, and the substituent at position 5 of the pyrimidine
      nucleobase.

PMID- 24462849
TI  - Synthesis of 2-{2-[(alpha/beta-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl}
      acetamides with 11beta-hydroxysteroid dehydrogenase inhibition and in combo
      antidiabetic activities.
AB  - Compounds 1-10 were designed using a bioisosteric approach and were prepared
      using a short synthetic route. The in vitro inhibitory activity of the compounds
      against 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) was evaluated.
      Compounds 5 (alpha-series) and 10 (beta-series) had a moderate inhibitory enzyme
      activity (55.26% and 67.03% inhibition at 10 MUM, respectively) and were as
      active as BVT.14225 (positive control). Both compounds have a piperidine ring in
      their structure, but the most active (10) was selected to establish its in vivo
      antidiabetic effect using a non insulin-dependent diabetes mellitus rat model.
      The antidiabetic activity of compound 10 was determined at 50 mg/kg single dose
      in an acute model, and also by short term sub-chronic administration for 5 days.
      The results indicated a significant decrease of plasma glucose levels, similar
      than BVT.14225. Additionally, a molecular docking of the most active compounds of
      each series into the ligand binding pocket of one subunit of human 11beta-HSD1
      was performed. In this model the oxygen atom of the sulfonamide make hydrogen
      bond interactions with the catalytic residues Ser170 and Ala172. We also observed
      important pi-pi interactions between the naphthyl group and Tyr177.

PMID- 24462851
TI  - Quality outcomes after hysterectomy.

PMID- 24462850
TI  - Comparison of the use of LigaSure, HALO PKS cutting forceps, and ENSEAL tissue
      sealer in total laparoscopic hysterectomy: a randomized trial.
AB  - STUDY OBJECTIVE: There are many instruments with different energy modalities or
      with different properties that are available for use in total laparoscopic
      hysterectomy. The aim of the study was to compare the use of LigaSure (Valleylab,
      Boulder, CO), HALO PKS cutting forceps (Gyrus-ACMI, Maple Grove, MA), and ENSEAL
      tissue sealer (SurgRx, Inc. Redwood City, CA) in total laparoscopic hysterectomy
      with respect to operation time and blood loss as main outcomes. Perioperative
      complications, return of gastrointestinal activity, and hospitalization time were
      assessed as secondary outcomes. DESIGN: Randomized prospective study (Canadian
      Task Force classification I). SETTING: Adana Numune Training and Research
      Hospital. PATIENTS: Forty-five patients with the indication of hysterectomy were
      randomized into 3 groups for total laparoscopic hysterectomy. Patients with
      malignancies, having 3 or more previous abdominal surgeries, a uterus larger than
      12 weeks of gestation, and who had to undergo additional surgical procedures
      during the same operation were excluded. INTERVENTIONS: Total laparoscopic
      hysterectomy. MEASUREMENTS AND MAIN RESULTS: Operations were completed in all 15
      patients in the LigaSure and HALO PKS Cutting Forceps groups with the planned
      instruments. In 2 patients in the ENSEAL group, bleeding could not be controlled
      with ENSEAL, and additional instruments were used. One patient in the ENSEAL
      group had bladder injury. The mean operation time and blood loss were 52.4 +/-
      12.8, 51.86 +/- 14.11, and 55.7 +/- 15.7 minutes (p > .05) and 138 +/- 54.3, 118
      +/- 63.3, and 218 +/- 115.9 mL (p < .05) in the LigaSure, HALO PKS, and ENSEAL
      groups, respectively. Changes in hemoglobin/hematocrit levels, return of
      gastrointestinal activity, and hospitalization time did not differ between
      groups. CONCLUSION: These 3 novel bipolar platforms had similar results in total
      laparoscopic hysterectomy. These instruments were not determined to be
      independent predictors of operating time and amount of blood loss.

PMID- 24462852
TI  - Single-site laparoscopic radical hysterectomy using conventional ports and
      instruments.
AB  - STUDY OBJECTIVE: To study the technical feasibility of performing a radical
      hysterectomy via laparoscopic single-site surgery LESS. PATIENT: A 45-year-old
      woman with cervical cancer stage IA2. INTERVENTION: Biopsy report showed invasive
      keratinizing squamous cell carcinoma, grade II. We duplicated the steps of our
      "Pune technique" of laparoscopic radical hysterectomy to perform a radical
      hysterectomy via laparoscopic single-site surgery using conventional ports and
      instruments. MEASUREMENTS AND MAIN RESULTS: Oncologic clearance was comparable to
      that of conventional laparoscopic radical hysterectomy. Operative time was 120
      minutes, and blood loss was 50 mL. CONCLUSION: Reduced port laparoscopic radical
      hysterectomy is technically feasible. Oncologic clearance and functional results
      are comparable to those of the multiport variant, with good cosmetic results.

PMID- 24462853
TI  - Recurrent ovarian torsion in a pregnancy complicated by ovarian hyperstimulation
      syndrome.

PMID- 24462854
TI  - Trends in the national distribution of laparoscopic hysterectomies from 2003 to
      2010.
AB  - STUDY OBJECTIVE: The purpose of this analysis was to compare the trends in
      undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy)
      based on patient age, race, median income and insurance type, from 2003 to 2010.
      DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING:
      National sample of hospital admissions after hysterectomy. PATIENTS: Health Cost
      and Utilization Project-Nationwide Inpatient Sample database was used to review
      records of women who underwent hysterectomy for either menorrhagia or leiomyoma
      from 2003-2010. INTERVENTION: The predicted probability of undergoing
      laparoscopic hysterectomy was determined for each year according to patient age,
      race, median income, and insurance type. The slopes of these values (i.e. the
      trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these
      categories. MAIN RESULTS: A total of 530, 154 cases were included in this study.
      Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003
      to 2010. The percent of hysterectomies that were laparoscopic increased from 11%
      in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted
      probability of undergoing a laparoscopic hysterectomy. Of all women undergoing
      hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained
      highest for women who were less than 35 years old, white, with the highest median
      income, and with private insurance from 2003-2010. The slope was significantly
      greater for (1) white females versus all other races analyzed (p<0.01), (2)
      females in the highest income quartile versus females in the lowest income
      quartile (p<0.01) and (3) females with private insurance versus females with
      Medicaid (p<0.01) or Medicare (p<0.01). CONCLUSIONS: There remains a gap in
      distribution of laparoscopic hysterectomies with regards to age, race, median
      income and insurance type that does not seem to be closing, despite the increased
      availability of laparoscopic hysterectomies.

PMID- 24462855
TI  - Nonsurgical management of live tubal ectopic pregnancy by ultrasound-guided local
      injection and systemic methotrexate.
AB  - STUDY OBJECTIVE: To evaluate outcomes relative to treatment using systemic
      methotrexate (MTX) alone or systemic MTX combined with ultrasound (US)-guided
      local injection of potassium chloride (KCl) or MTX in women with live tubal
      ectopic pregnancies. DESIGN: Case-control study (Canadian Task Force
      classification II-2). SETTING: Departments of Obstetrics and Gynecology in 2
      hospitals in China. PATIENTS: Eighty-two women with live tubal ectopic
      pregnancies. INTERVENTION: Participants in the study received treatment using
      either systemic MTX (n = 37; systemic treatment group) or systemic MTX and US
      guided local injection of either MTX or KCl (n = 45; combined treatment group).
      MEASUREMENTS AND MAIN RESULTS: Patient clinical features and outcomes were
      compared. There were no significant differences between the patient groups
      insofar as baseline gestational age, beta-human chorionic gonadotropin
      concentration, or size of conceptus. The success rate in patients who received
      combined therapy (93.3%) was much higher than in those who received only systemic
      treatment (73.0%) (p < .05). In the combined treatment group, the success rate
      was similar between women who received locally injected KCl (95.2%) and those who
      received locally injected MTX (91.7%). CONCLUSION: The significantly higher
      success rate in patients who received combined US-guided local injection and
      systemic MTX suggests that this is an efficient nonsurgical option in women with
      tubal pregnancy, high serum beta-human chorionic gonadotropin concentration, and
      fetal cardiac activity.

PMID- 24462856
TI  - Use of a multimedia module to aid the informed consent process in patients
      undergoing gynecologic laparoscopy for pelvic pain: randomized controlled trial.
AB  - STUDY OBJECTIVE: To determine whether providing additional information to the
      standard consent process, in the form of a multimedia module (MM), improves
      patient knowledge about operative laparoscopy without increasing anxiety. DESIGN:
      Randomized controlled trial (Canadian Task Force classification I). SETTING: Two
      outpatient gynecologic clinics, one in a private hospital and the other in a
      public teaching hospital. PATIENTS: Forty-one women aged 19 to 51 years (median,
      35.6 years) requiring operative laparoscopy for investigation and treatment of
      pelvic pain. INTERVENTION: Following the standard informed consent process,
      patients were randomized to watch the MM (intervention group, n = 21) or not
      (control group, n = 20). The surgeon was blinded to the group assignments. All
      patients completed a knowledge questionnaire and the Spielberger short-form State
      Trait Anxiety Inventory. Six weeks after recruitment, patients completed the
      knowledge questionnaire and the State-Trait Anxiety Inventory a second time to
      assess knowledge retention and anxiety scores. MEASUREMENTS AND MAIN RESULTS:
      Patient knowledge of operative laparoscopy, anxiety level, and acceptance of the
      MM were recorded. The MM intervention group demonstrated superior knowledge
      scores. Mean (SE) score in the MM group was 11.3 (0.49), and in the control group
      was 7.9 (0.50) (p <.001) (maximum score, 14). This did not translate into
      improved knowledge scores 6 weeks later; the score in the MM group was 8.4 (0.53)
      vs. 7.8 (0.50) in the control group (p = .44). There was no difference in anxiety
      levels between the groups at intervention or after 6 weeks. Overall, patients
      found the MM acceptable, and 18 women (86%) in the intervention group and 12
      (60%) in the control group stated they would prefer this style of informed
      consent in the future. CONCLUSION: Use of an MM enhances the informed consent
      process by improving patient knowledge, in the short term, without increasing
      anxiety.

PMID- 24462857
TI  - Corticosteroids modulate the expression of the PKC-anchoring protein RACK-1 and
      cytokine release in THP-1 cells.
AB  - We demonstrated that cortisol reduces the expression of RACK-1 (Receptor for
      Activated C Kinase-1), a protein required for immune cell activation. The aim of
      this study was to evaluate whether and to what extent other clinically relevant
      corticosteroids may modulate RACK-1 expression. We used the human promyelocytic
      cell line THP-1 to investigate the effects of cortisol, prednisone, prednisolone,
      budesonide, betamethasone and methylprednisolone on RACK-1 expression and
      cytokine production. As anticipated, all corticosteroids inhibited at non
      cytotoxic concentrations in a dose and time related manner LPS-induced TNF-alpha
      and IL-8 release, with budesonide, betamethasone and methylprednisolone being the
      most active followed by prednisolone, cortisol and prednisone. To a similar
      extent, all corticosteroids also reduced RACK-1 mRNA expression and RACK-1
      protein levels as assessed by Real Time PCR and Western blot, respectively.
      Prednisone was the least potent compound while betamethasone and
      methylprednisolone where the most active. A good correlation was observed between
      RACK-1 mRNA or protein levels and cytokine release (Pearson r=0.7376, p=0.0471
      for RACK-1 mRNA and TNF-alpha release, and Pearson r=0.8108, p=0.0252 for RACK-1
      protein and IL-8 release). Mifepristone, a potent glucocorticoid receptor (GR)
      antagonist, completely prevented the effect of cortisol, demonstrating that RACK
      1 downregulation is via GR. Furthermore, to by-pass the defective PKC activation
      due to the decrease in RACK-1, we used a RACK-1 pseudosubstrate, that directly
      activates PKC-beta. RACK-1 pseudosubstrate was able to restore LPS-induced
      cytokine production affected by cortisol, supporting the role of RACK-1 in the
      anti-inflammatory effect of corticosteroids. These results confirm the
      involvement of RACK-1 in immune cell activation and identify this protein as a
      novel transcriptional target of corticosteroid-induced anti-inflammatory effects.

PMID- 24462858
TI  - Single-step generation of gene knockout-rescue system in pluripotent stem cells
      by promoter insertion with CRISPR/Cas9.
AB  - Specific gene knockout and rescue experiments are powerful tools in developmental
      and stem cell biology. Nevertheless, the experiments require multiple steps of
      molecular manipulation for gene knockout and subsequent rescue procedures. Here
      we report an efficient and single step strategy to generate gene knockout-rescue
      system in pluripotent stem cells by promoter insertion with CRISPR/Cas9 genome
      editing technology. We inserted a tetracycline-regulated inducible gene promoter
      (tet-OFF/TRE-CMV) upstream of the endogenous promoter region of vascular
      endothelial growth factor receptor 2 (VEGFR2/Flk1) gene, an essential gene for
      endothelial cell (EC) differentiation, in mouse embryonic stem cells (ESCs) with
      homologous recombination. Both homo- and hetero-inserted clones were efficiently
      obtained through a simple selection with a drug-resistant gene. The insertion of
      TRE-CMV promoter disrupted endogenous Flk1 expression, resulting in null mutation
      in homo-inserted clones. When the inserted TRE-CMV promoter was activated with
      doxycycline (Dox) depletion, Flk1 expression was sufficiently recovered from the
      downstream genomic Flk1 gene. Whereas EC differentiation was almost completely
      perturbed in homo-inserted clones, Flk1 rescue with TRE-CMV promoter activation
      restored EC appearance, indicating that phenotypic changes in EC differentiation
      can be successfully reproduced with this knockout-rescue system. Thus, this
      promoter insertion strategy with CRISPR/Cas9 would be a novel attractive method
      for knockout-rescue experiments. 

PMID- 24462859
TI  - Homeobox B9 is overexpressed in hepatocellular carcinomas and promotes tumor cell
      proliferation both in vitro and in vivo.
AB  - HomeoboxB9 (HOXB9), a nontransforming transcription factor that is overexpressed
      in multiple tumor types, alters tumor cell fate and promotes tumor progression.
      However, the role of HOXB9 in hepatocellular carcinoma (HCC) development has not
      been well studied. In this paper, we found that HOXB9 is overexpressed in human
      HCC samples. We investigated HOXB9 expression and its prognostic value for HCC.
      HCC surgical tissue samples were taken from 89 HCC patients. HOXB9 overexpression
      was observed in 65.2% of the cases, and the survival analysis showed that the
      HOXB9 overexpression group had significantly shorter overall survival time than
      the HOXB9 downexpression group. The ectopic expression of HOXB9 stimulated the
      proliferation of HCC cells; whereas the knockdown of HOXB9 produced an opposite
      effect. HOXB9 also modulated the tumorigenicity of HCC cells in vivo. Moreover,
      we found that the activation of TGF-beta1 contributes to HOXB9-induced
      proliferation activities. The results provide the first evidence that HOXB9 is a
      critical regulator of tumor growth factor in HCC. 

PMID- 24462860
TI  - Growth differentiation factor-15 induces expression of ATP-binding cassette
      transporter A1 through PI3-K/PKCzeta/SP1 pathway in THP-1 macrophages.
AB  - OBJECTIVE: The aim of this study was to determine whether ATP-binding cassette
      transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF
      15) via the phosphoinositide 3-kinase (PI3K)/protein kinase Czeta
      (PKCzeta)/specificity protein 1 (SP1) pathway in THP-1 macrophages. METHODS AND
      RESULTS: We investigated the effects of different concentrations of GDF-15 on
      ABCA1 expression in THP-1 macrophages. The results showed that GDF-15
      dramatically increased cholesterol efflux and decreased cellular cholesterol
      levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects
      of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were
      abolished by wither inhibition or depletion of PI3K, PKCzeta and SP1,
      respectively, suggesting the potential roles of PI3K, PKCzeta and SP1 in ABCA1
      expression. Taken together, GDF-15 appears to activate PI3K, PKCzeta and SP1
      cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux
      and reducing foam cell formation. CONCLUSION: Our results suggest that GDF-15 has
      an overall protective effect on the progression of atherosclerosis, likely
      through inducing ABCA1 expression via the PI3K/PKCzeta/SP1 signaling pathway and
      enhancing cholesterol efflux.

PMID- 24462861
TI  - Effect of hyperglycemia on insulin receptor signaling in the cultured retinal
      Muller glial cells.
AB  - Hyperglycemia and impaired insulin signaling are considered as major factors in
      the retinal pathology in diabetic retinopathy (DR). Numerous reports support that
      these two factors damage retinal glial as well as neuronal cells early in
      diabetes. However, it is not known whether diabetic induced hyperglycemia causes
      a depression to the insulin signaling. In this study we utilized a well
      characterized cultured Muller cells (TR-MUL) where we found a high expression of
      insulin receptor molecules. TR-MUL Cells were treated with high glucose,
      glutamate and hydrogen peroxide, and activated with insulin. Following
      treatments, cell lysates were analyzed by immunoblotting experiments for insulin
      receptor (IRbeta) and insulin receptor substrate (IRS1). In addition, cell
      lysates were immunoprecipitated using antibodies against insulin receptor
      proteins to analyze tyrosine phosphorylation and serine phosphorylation of
      insulin receptor proteins. Results indicate that hyperglycemia did not affect the
      expression of insulin receptor proteins in cultured TR-MUL cells. Although,
      hyperglycemia seems to inhibit the interaction between IRS1 and IRbeta. Hydrogen
      peroxide increased the tyrosine phosphorylation of insulin receptor proteins but
      excess glutamate could not affect the insulin receptor proteins indicating that
      glutamate may not cause oxidative stress in TR-MUL cells. Hyperglycemia lowered
      serine phosphorylation of IRS(ser632) and IRS(ser1101) however, IRS(ser307) was
      not affected. Thus, hyperglycemia may not affect insulin signaling through
      tyrosine phosphorylation of insulin receptor proteins but may inhibit the
      interactions between insulin receptor proteins. Hyperglycemia induced
      phosphorylation of various serine residues of IRS1 and their influence on insulin
      signaling needs further investigation in TR-MUL cells. 

PMID- 24462862
TI  - OX40 ligand regulates splenic CD8- dendritic cell-induced Th2 responses in vivo.
AB  - In mice, splenic conventional dendritic cells (cDCs) can be separated, based on
      their expression of CD8alpha into CD8(-) and CD8(+) cDCs. Although previous
      experiments demonstrated that injection of antigen (Ag)-pulsed CD8(-) cDCs into
      mice induced CD4 T cell differentiation toward Th2 cells, the mechanism involved
      is unclear. In the current study, we investigated whether OX40 ligand (OX40L) on
      CD8(-) cDCs contributes to the induction of Th2 responses by Ag-pulsed CD8(-)
      cDCs in vivo, because OX40-OX40L interactions may play a preferential role in Th2
      cell development. When unseparated Ag-pulsed OX40L-deficient cDCs were injected
      into syngeneic BALB/c mice, Th2 cytokine (IL-4, IL-5, and IL-10) production in
      lymph node cells was significantly reduced. Splenic cDCs were separated to CD8(-)
      and CD8(+) cDCs. OX40L expression was not observed on freshly isolated CD8(-)
      cDCs, but was induced by anti-CD40 mAb stimulation for 24 h. Administration of
      neutralizing anti-OX40L mAb significantly inhibited IL-4, IL-5, and IL-10
      production induced by Ag-pulsed CD8(-) cDC injection. Moreover, administration of
      anti-OX40L mAb with Ag-pulsed CD8(-) cDCs during a secondary response also
      significantly inhibited Th2 cytokine production. Thus, OX40L on CD8(-) cDCs
      physiologically contributes to the development of Th2 cells and secondary Th2
      responses induced by Ag-pulsed CD8(-) cDCs in vivo.

PMID- 24462863
TI  - IQGAP1 selectively interacts with K-Ras but not with H-Ras and modulates K-Ras
      function.
AB  - K-Ras is frequently mutated and activated especially in pancreatic cancers. To
      analyze K-Ras function, we have searched for K-Ras interacting proteins and found
      IQ motif containing GTPase activating protein 1 (IQGAP1) as a novel K-Ras binding
      protein. IQGAP1 has been known as a scaffold protein for B-Raf, MEK1/2 and
      ERK1/2. Here we showed that IQGAP1 selectively formed a complex with K-Ras but
      not with H-Ras, and recruited B-Raf to K-Ras. We found that IQ motif region of
      IQGAP1 interacted with K-Ras. Both active and inactive K-Ras interacted with
      IQGAP1, and effector domain mutants of K-Ras also associated with IQGAP1,
      indicating that IQGAP1 interacts with K-Ras irrespective of Ras-effectors like B
      Raf. We also found that overexpression or knock-down of IQGAP1 affected the
      interaction between K-Ras and B-Raf, and IQGAP1 overexpression increased ERK1/2
      phosphorylation in K-Ras dependent manner in PANC1 cells. Our data suggest that
      IQGAP1 has a novel mechanism to modulate K-Ras pathway. 

PMID- 24462864
TI  - TRPM2 contributes to LPS/IFNgamma-induced production of nitric oxide via the
      p38/JNK pathway in microglia.
AB  - Microglia are immune cells that maintain brain homeostasis at a resting state by
      surveying the environment and engulfing debris. However, in some pathological
      conditions, microglia can produce neurotoxic factors such as pro-inflammatory
      cytokines and nitric oxide (NO) that lead to neuronal degeneration. Inflammation
      induced calcium (Ca(2+)) signaling is thought to underlie this abnormal
      activation of microglia, but the mechanisms are still obscure. We previously
      showed that combined application of lipopolysaccharide and interferon gamma
      (LPS/IFNgamma) induced-production of NO in microglia from wild-type (WT) mice is
      significantly reduced in microglia from transient receptor potential melastatin 2
      (TRPM2)-knockout (KO) mice. Here, we found that LPS/IFNgamma produced a late
      onset Ca(2+) signaling in WT microglia, which was abolished by application of the
      NADPH oxidase inhibitor diphenylene iodonium (DPI) and ML-171. In addition,
      pharmacological blockade or gene deletion of TRPM2 channel in microglia did not
      show this Ca(2+) signaling. Furthermore, pharmacological manipulation and Western
      blotting revealed that Ca(2+) mobilization, the proline-rich tyrosine kinase 2
      (Pyk2), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal
      kinase (JNK) contributed to TRPM2-mediated LPS/IFNgamma-induced activation, while
      the extracellular signal-regulated protein kinase (ERK) did not. These results
      suggest that LPS/IFNgamma activates TRPM2-mediated Ca(2+) signaling, which in
      turn increases downstream p38 MAPK and JNK signaling and results in increased NO
      production in microglia. 

PMID- 24462865
TI  - Salvianolic acid B protects cardiomyocytes from angiotensin II-induced
      hypertrophy via inhibition of PARP-1.
AB  - Salvianolic acid B (SalB), one of the major bioactive components in
      Salviamiltiorrhiza, has plenty of cardioprotective effects. The present study was
      designed to investigate the effect of SalB on angiotensin II (AngII)-induced
      hypertrophy in neonatal rat cardiomyocytes, and to find out whether or not this
      effect is attributed to inhibition of poly (ADP-ribose) polymerase-1 (PARP-1),
      which plays a key role in cardiac hypertrophy. Our results showed that SalB
      prevented the cardiomyocytes from AngII-induced hypertrophy, associated with
      attenuation of the mRNA expressions of atrial natriuretic factor and brain
      natriuretic peptide, and reduction in the cell surface area. SalB inhibited the
      activity of PARP-1. The inhibitory effect was comparable to that of the PARP-1
      inhibitor 3-Aminobenzamide (3-AB). In addition, SalB reversed the depletion of
      cellular NAD(+) induced by AngII. Moreover, overexpression of PARP-1 attenuated
      the anti-hypertrophic effect of SalB. These observations suggested that SalB
      prevented the cardiomyocytes from AngII-induced hypertrophy, at least partially
      through inhibition of PARP-1. Moreover, SalB attenuated the generation of
      oxidative stress via suppression of NADPH oxidase 2 and 4, which might probably
      contribute to the inhibition of PARP-1. These present findings may shed new light
      on the understanding of the cardioprotective effect of SalB. 

PMID- 24462866
TI  - Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR
      inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis
      and autophagy.
AB  - Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its
      mechanism of action is unclear. Cisplatin (DDP) is currently the best known
      chemotherapeutic available for ovarian cancer. However, tumors return de novo
      with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an
      important kinase that regulates cell apoptosis and autophagy, and its
      dysregulation has been observed in chemoresistant human cancers. Here, we show
      that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was
      abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP)
      following cisplatin monotherapy. Treatment with cisplatin combined with DHA could
      enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This
      mechanism is at least partially due to DHA deactivation of mTOR kinase and
      promotion of apoptosis. Although autophagy was also induced by DHA, the reduced
      cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF).
      Taken together, we conclude that inhibition of cisplatin-induced mTOR activation
      is one of the main mechanisms by which DHA dramatically promotes its anticancer
      effect in cisplatin-resistant ovarian cancer cells. 

PMID- 24462867
TI  - miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via
      increasing PTEN expression.
AB  - MicroRNAs (miRNAs) play essential roles in cancer development and progression.
      Here, we investigated the role of miR-17 in the progression and metastasis of
      osteosarcoma (OS). miR-17 was frequently increased in OS tissues and cell lines.
      Inhibition of miR-17 in OS cell lines substantially suppressed cell
      proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was
      identified as a target of miR-17, and ectopic expression of miR-17 inhibited PTEN
      by direct binding to its 3'-untranslated region (3'-UTR). Expression of miR-17
      was negatively correlated with PTEN in OS tissues. Together, these findings
      indicate that miR-17 acts as an oncogenic miRNA and may contribute to the
      progression and metastasis of OS, suggesting miR-17 as a potential novel
      diagnostic and therapeutic target of OS. 

PMID- 24462868
TI  - Hydroxylamine enhances glucose uptake in C2C12 skeletal muscle cells through the
      activation of insulin receptor substrate 1.
AB  - Diabetes mellitus is a global disease, and the number of patients with it is
      increasing. Of various agents for treatment, those that directly act on muscle
      are currently attracting attention because muscle is one of the main tissues in
      the human body, and its metabolism is decreased in type II diabetes. In this
      study, we found that hydroxylamine (HA) enhances glucose uptake in C2C12
      myotubes. Analysis of HA's mechanism revealed the involvement of IRS1, PI3K and
      Akt that is related to the insulin signaling pathway. Further investigation about
      the activation mechanism of insulin receptor or IRS1 by HA may provide a way to
      develop a novel anti-diabetic agent alternating to insulin. 

PMID- 24462869
TI  - Retroviral vectors for homologous recombination provide efficient cloning and
      expression in mammalian cells.
AB  - Homologous recombination technologies enable high-throughput cloning and the
      seamless insertion of any DNA fragment into expression vectors. Additionally,
      retroviral vectors offer a fast and efficient method for transducing and
      expressing genes in mammalian cells, including lymphocytes. However, homologous
      recombination cannot be used to insert DNA fragments into retroviral vectors;
      retroviral vectors contain two homologous regions, the 5'- and 3'-long terminal
      repeats, between which homologous recombination occurs preferentially. In this
      study, we have modified a retroviral vector to enable the cloning of DNA
      fragments through homologous recombination. To this end, we inserted a bacterial
      selection marker in a region adjacent to the gene insertion site. We used the
      modified retroviral vector and homologous recombination to clone T-cell receptors
      (TCRs) from single Epstein Barr virus-specific human T cells in a high-throughput
      and comprehensive manner and to efficiently evaluate their function by
      transducing the TCRs into a murine T-cell line through retroviral infection. In
      conclusion, the modified retroviral vectors, in combination with the homologous
      recombination method, are powerful tools for the high-throughput cloning of cDNAs
      and their efficient functional analysis. 

PMID- 24462870
TI  - Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies
      microRNAs expression profiles in human colorectal cancer cells.
AB  - Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies
      including colorectal cancer (CRC), has been reported to be associated with the
      carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and
      progression of cancer. However, the functional significance of AEG-1 and the
      relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of
      this study was to investigate whether AEG-1 could serve as a potential
      therapeutic target of human CRC and its possible mechanism. We adopted a strategy
      of ectopic overexpression or RNA interference to upregulate or downregulate
      expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by
      Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression
      profiles were performed using microarray analysis followed by validation using
      qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell
      proliferation, colony formation, invasion and promotes apoptosis. Conversely,
      upregulation of AEG-1 could significantly enhance cell proliferation, invasion
      and reduced apoptisis. AEG-1 directly contributes to resistance to
      chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the
      expression of miR-181a-2(*), -193b and -193a, and inversely inhibit miR-31 and 
      9(*). Targeted inhibition of AEG-1 can lead to modification of key elemental
      characteristics, such as miRNAs, which may become a potential effective
      therapeutic strategy for CRC. 

PMID- 24462871
TI  - Crystal structure and biochemical characterization of beta-keto thiolase B from
      polyhydroxyalkanoate-producing bacterium Ralstonia eutropha H16.
AB  - ReBktB is a beta-keto thiolase from Ralstonia eutropha H16 that catalyzes
      condensation reactions between acetyl-CoA with acyl-CoA molecules that contains
      different numbers of carbon atoms, such as acetyl-CoA, propionyl-CoA, and butyryl
      CoA, to produce valuable bioproducts, such as polyhydroxybutyrate,
      polyhydroxybutyrate-hydroxyvalerate, and hexanoate. We solved a crystal structure
      of ReBktB at 2.3A, and the overall structure has a similar fold to that of type
      II biosynthetic thiolases, such as PhbA from Zoogloea ramigera (ZrPhbA). The
      superposition of this structure with that of ZrPhbA complexed with CoA revealed
      the residues that comprise the catalytic and substrate binding sites of ReBktB.
      The catalytic site of ReBktB contains three conserved residues, Cys90, His350,
      and Cys380, which may function as a covalent nucleophile, a general base, and
      second nucleophile, respectively. For substrate binding, ReBktB stabilized the
      ADP moiety of CoA in a distinct way compared to ZrPhbA with His219, Arg221, and
      Asp228 residues, whereas the stabilization of beta-mercaptoethyamine and
      pantothenic acid moieties of CoA was quite similar between these two enzymes.
      Kinetic study of ReBktB revealed that K(m), V(max), and K(cat) values of 11.58
      MUM, 1.5 MUmol/min, and 102.18 s(-1), respectively, and the catalytic and
      substrate binding sites of ReBktB were further confirmed by site-directed
      mutagenesis experiments.

PMID- 24462872
TI  - Absence of superoxide dismutase activity causes nuclear DNA fragmentation during
      the aging process.
AB  - Superoxide dismutases (SOD) serve as an important antioxidant defense mechanism
      in aerobic organisms, and deletion of these genes shortens the replicative life
      span in the budding yeast Saccharomyces cerevisiae. Even though involvement of
      superoxide dismutase enzymes in ROS scavenging and the aging process has been
      studied extensively in different organisms, analyses of DNA damages has not been
      performed for replicatively old superoxide dismutase deficient cells. In this
      study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving
      genomic integrity in replicatively old yeast cells using the single cell comet
      assay. We observed that extend of DNA damage was not significantly different
      among the young cells of wild type, sod1Delta and sod2Delta strains. However,
      ccs1Delta mutants showed a 60% higher amount of DNA damage in the young stage
      compared to that of the wild type cells. The aging process increased the DNA
      damage rates 3-fold in the wild type and more than 5-fold in sod1Delta,
      sod2Delta, and ccs1Delta mutant cells. Furthermore, ROS levels of these strains
      showed a similar pattern to their DNA damage contents. Thus, our results confirm
      that cells accumulate DNA damages during the aging process and reveal that
      superoxide dismutase enzymes play a substantial role in preserving the genomic
      integrity in this process. 

PMID- 24462873
TI  - Effect of adiponectin on cardiac beta-catenin signaling pathway under angiotensin
      II infusion.
AB  - Obesity is associated with heart failure and cardiac hypertrophy. Adiponectin has
      been shown to play a protective role for cardiovascular diseases. The beta
      catenin signaling pathway is deeply involved in cardiac hypertrophy. However, the
      effect of adiponectin on beta-catenin signaling has not been investigated in
      cardiac hypertrophy. Present study aimed to clarify the involvement of
      adiponectin and beta-catenin signaling pathway in the mouse model of angiotensin
      II (AngII)-induced cardiac hypertrophy. In hearts of Wild type (WT) mice, AngII
      dose-dependently augmented cytosolic beta-catenin protein level. WT and
      adiponectin knockout (Adipo-KO) mice were administered with AngII at 2.4
      mg/kg/day for 14 days and were also injected with adenovirus expressing the
      adiponectin (Ad-Adipo) or the beta-galactosidase (Ad-betagal). Cardiac mRNA
      levels relating to hypertrophy and beta-catenin signaling were increased in Adipo
      KO mice and these changes were reversed by Ad-Adipo. Phosphorylation of Akt was
      increased in Adipo-KO mice and such increases were reversed by Ad-Adipo.
      Furthermore, the phosphorylation of glycogen synthase kinase 3beta (GSK3beta) at
      Ser(9) and cytosolic beta-catenin level were increased in Adipo-KO mice and they
      were significantly reduced by Ad-Adipo treatment. Phosphorylation of mammalian
      target of rapamycin (mTOR) was reduced by Ad-Adipo-mediated adiponectin
      supplementation in WT and Adipo-KO mice. The current study suggests that
      adiponectin attenuates AngII-induced cardiac hypertrophic signals partly through
      Akt/GSK3beta/beta-catenin and Akt/mTOR pathways.

PMID- 24462875
TI  - CagA, a major virulence factor of Helicobacter pylori, promotes the production
      and underglycosylation of IgA1 in DAKIKI cells.
AB  - While Helicobacter pylori (Hp) infection is closely associated with IgA
      nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated.
      This study was to investigate the effect of cytotoxin associated gene A protein
      (CagA), a major virulence factor of Hp, on the production and underglycosylation
      of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with
      recombinant CagA protein. We found that CagA stimulated cell proliferation and
      the production of IgA1 in a dose-dependent and time-dependent manner. Moreover,
      CagA promoted the underglycosylation of IgA1, which at least partly attributed to
      the downregulation of beta1,3-galactosyltransferase (C1GALT1) and its chaperone
      Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may
      participate in the pathogenesis of IgAN by influencing the production and
      glycosylation of IgA1 in B cells. 

PMID- 24462874
TI  - Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against
      apoptosis induced by the extrinsic pathway.
AB  - Reactive oxygen species (ROS) including hydrogen peroxide (H2O2) exhibit both pro
      survival and pro-death signaling in leukemic cells. We examined the effect of
      exogenous H2O2 on Fas ligand (FasL) -induced apoptosis in Jurkat cells. H2O2
      applied prior to (pre-conditioning) and during (post-conditioning) FasL
      stimulation attenuated early apoptosis through activation of EKR5. H2O2 increased
      the activated caspase-8 sequestered in the mitochondria thereby decreasing cell
      death through the extrinsic apoptotic pathway. In addition, inhibition of a
      protein tyrosine phosphatase likely explains the post-conditioning requirement
      for H2O2. Given that chemotherapeutic agents used for the treatment of acute
      lymphoblastic leukemia are thought to work partly through production of ROS, a
      simultaneous inhibition of the ERK5 pathway may abrogate the ROS-initiated pro
      survival signaling for an enhanced cell kill.

PMID- 24462876
TI  - Fibronectin and transforming growth factor beta contribute to erythropoietin
      resistance and maladaptive cardiac hypertrophy.
AB  - The use of recombinant human erythropoietin (rhEPO) to promote repair and
      minimize cardiac hypertrophy after myocardial infarction has had disappointing
      outcomes in clinical trials. We hypothesized that the beneficial non
      hematopoietic effects of rhEPO against cardiac hypertrophy could be offset by the
      molecular changes initiated by rhEPO itself, leading to rhEPO resistance or
      maladaptive hypertrophy. This hypothesis was investigated using an isoproterenol
      induced model of myocardial infarct and cardiac remodelling with emphasis on
      hypertrophy. In h9c2 cardiomyocytes, rhEPO decreased isoproterenol-induced
      hypertrophy, and the expression of the pro-fibrotic factors fibronectin, alpha
      smooth muscle actin and transforming growth factor beta-1 (TGF-beta1). In
      contrast, by itself, rhEPO increased the expression of fibronectin and TGF-beta1.
      Exogenous TGF-beta1 induced a significant increase in hypertrophy, which was
      further potentiated by rhEPO. Exogenous fibronectin not only induced hypertrophy
      of cardiomyocytes, but also conferred resistance to rhEPO treatment. Based on
      these findings we propose that the outcome of rhEPO treatment for myocardial
      infarction is determined by the baseline concentrations of fibronectin and TGF
      beta1. If endogenous fibronectin or TGF-beta levels are above a certain
      threshold, they could cause resistance to rhEPO therapy and enhancement of
      cardiac hypertrophy, respectively, leading to maladaptive hypertrophy. 

PMID- 24462877
TI  - Atrial natriuretic peptide inhibits lipopolysaccharide-induced acute lung injury.
AB  - OBJECTIVES: We recently reported that administration of atrial natriuretic
      peptide during the perioperative period has prophylactic effects with respect to
      not only cardiovascular but also respiratory complications following pulmonary
      resection. However, its mechanisms are not well understood. The objective of the
      present study was to investigate the mechanism of the prophylactic effects of
      atrial natriuretic peptide in an acute lung injury model. METHODS: For the
      evaluation of the early phase of pulmonary inflammation, in vitro and in vivo
      studies using lipopolysaccharide were used. In the in vitro study, the effects of
      atrial natriuretic peptide on the induction of E-selectin by lipopolysaccharide
      in human pulmonary artery endothelial cells were evaluated. In the in vivo study,
      the effects of atrial natriuretic peptide on lipopolysaccharide-induced
      inflammatory cell infiltration and cytokine levels including tumor necrosis
      factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid in the lungs
      of C57/B6 mice were examined. The number of myeloperoxidase-positive staining
      cells in the tissue sections of the lung of lipopolysaccharide-administered
      C57/B6 mice was also evaluated. RESULTS: Atrial natriuretic peptide significantly
      attenuated the up-regulation of E-selectin expression induced by
      lipopolysaccharide in human pulmonary artery endothelial cells. There were
      significantly lower cell counts and levels of tumor necrosis factor-alpha and
      interleukin-6 in the bronchoalveolar lavage fluid of atrial natriuretic peptide
      treated mice compared to control mice after lipopolysaccharide injection. In
      addition, there were significantly fewer myeloperoxidase-positive cells in atrial
      natriuretic peptide-treated mice than in control mice after lipopolysaccharide
      injection. CONCLUSIONS: Atrial natriuretic peptide had a protective effect in the
      lipopolysaccharide-induced acute lung injury model. Atrial natriuretic peptide
      may be of value in therapeutic strategies aimed at the treatment of acute lung
      injury such as pneumonia or acute respiratory distress syndrome.

PMID- 24462878
TI  - Temporal profiling of cytokine-induced genes in pancreatic beta-cells by meta
      analysis and network inference.
AB  - Type 1 Diabetes (T1D) is an autoimmune disease where local release of cytokines
      such as IL-1beta and IFN-gamma contributes to beta-cell apoptosis. To identify
      relevant genes regulating this process we performed a meta-analysis of 8 datasets
      of beta-cell gene expression after exposure to IL-1beta and IFN-gamma. Two of
      these datasets are novel and contain time-series expressions in human islet cells
      and rat INS-1E cells. Genes were ranked according to their differential
      expression within and after 24 h from exposure, and characterized by function and
      prior knowledge in the literature. A regulatory network was then inferred from
      the human time expression datasets, using a time-series extension of a network
      inference method. The two most differentially expressed genes previously unknown
      in T1D literature (RIPK2 and ELF3) were found to modulate cytokine-induced
      apoptosis. The inferred regulatory network is thus supported by the experimental
      validation, providing a proof-of-concept for the proposed statistical inference
      approach.

PMID- 24462879
TI  - Ethanol fermentation of energy beets by self-flocculating and non-flocculating
      yeasts.
AB  - Specialized varieties of sugar beets (Energy BeetsTM) are being developed for
      producing industrial sugars in Arkansas' Mississippi River Delta. To evaluate
      their suitability for producing regional fermentation feedstocks, we report
      initial cultivation trials and ethanol fermentation of raw beet juice and
      combined juice with pulp mash (JPM) liquefied with enzymes, comparing ethanol
      yields under different regimes by self-flocculating and non-flocculating yeasts.
      Nine varieties produced root yields averaging 115Mg/ha and 18.5% sucrose
      contents. Raw beet juice fermentation yielded ethanol up to 0.48g/g (sugar). JPM
      was directly fermented through either a sequential (SeqSF) or simultaneous
      saccharification and fermentation (SSF) process. For both yeast types, SSF was a
      more efficient process than SeqSF, with ethanol yields up to 0.47g/g (sugar) and
      volumetric productivity up to 7.81g/L/h. These results indicate the self
      flocculating yeast is suitable for developing efficient bioprocesses to ferment
      industrial sugar from energy beets. 

PMID- 24462880
TI  - Improvement of methane production from waste activated sludge by on-site
      photocatalytic pretreatment in a photocatalytic anaerobic fermenter.
AB  - This paper reports a new technology that using on-site TiO2-photocatalytic
      pretreatment in the anaerobic digestion of waste activated sludge (WAS) can
      enhance WAS degradation and methane production in a novel photocatalytic
      anaerobic fermenter. The fermenter consists of a photocatalytic unit and a
      digestion unit. The photocatalytic unit can constantly supply soluble organics
      and has less negative effect on the activity of methanogens at the optimal
      photocatalytic time of 4h per day. After anaerobic digestion for 35days,
      1266.7ml/l-sludge of methane, 67.4% of volatile solid (VS) reduction and 60.5% of
      total chemical oxygen demand (TCOD) removal were achieved in the photocatalytic
      anaerobic fermenter, compared with 923.2ml/l-sludge of methane, 48.9% of VS
      reduction and 43.5% TCOD removal in the control fermenter. The results indicate
      that timely utilization of solubilized organics by methanogens could avoid
      further mineralization by TiO2-photocatalysis, which not only improves methane
      production but also enhances WAS degradation. 

PMID- 24462881
TI  - Comparison of the gaseous and particulate matter emissions from the combustion of
      agricultural and forest biomasses.
AB  - The aim of this study was to compare gaseous and particulate matter (PM)
      emissions from the combustion of agricultural (switchgrass, fast-growing willow
      and the dried solid fraction of pig manure) and forest (wood mixture of Black
      Spruce and Jack Pine) biomasses in a small-scale unit (17.58kW). Concentrations
      of CO2, CO, CH4, NO2, NH3, N2O, SO2, HCl, and H2O were measured by Fourier
      transform infrared spectroscopy and converted into emission rates. Opacity was
      also evaluated and particulates were sampled. Results showed significantly higher
      emissions of SO2, NO2 and PM with the combustion of agricultural biomass compared
      to the forest biomass. However, further studies should be carried out so
      regulations can be adapted in order to permit the combustion of agricultural
      biomass in small-scale combustion units. 

PMID- 24462882
TI  - Mesophilic and thermophilic anaerobic laboratory-scale digestion of
      Nannochloropsis microalga residues.
AB  - This paper studies methane production using a marine microalga, Nannochloropsis
      sp. residue from biodiesel production. Residue cake from Nannochloropsis, oils
      wet-extracted, had a methane potential of 482LCH4kg(-1) volatile solids (VS) in
      batch assays. However, when dry-extracted, the methane potential of residue cake
      was only 194LCH4kg(-1) VS. In semi-continuous reactor trials with dry-extracted
      residue cake, a thermophilic reactor produced 48% higher methane yield
      (220LCH4kg(-1)VS) than a mesophilic reactor (149LCH4kg(-1)VS). The thermophilic
      reactor was apparently inhibited due to ammonia with organic loading rate (OLR)
      of 2kgVSm(-3)d(-1) (hydraulic retention time (HRT) 46d), whereas the mesophilic
      reactor performed with OLR of 3kgVSm(-3)d(-1) (HRT 30d). Algal salt content did
      not inhibit digestion. Additional methane (18-33% of primary digester yield) was
      produced during 100d post-digestion. 

PMID- 24462883
TI  - An intragenic deletion of the NFIA gene in a patient with a hypoplastic corpus
      callosum, craniofacial abnormalities and urinary tract defects.
AB  - BACKGROUND: Chromosome 1p31 deletion (OMIM #613735) involving the NFIA gene (OMIM
      600727) is characterised by variable defects in the formation of the corpus
      callosum, craniofacial abnormalities and urinary tract defects. A review of
      current literature suggests only seven cases have been reported, none of which
      had an isolated NFIA gene defect. METHODS: We submit the clinical and molecular
      features of an 8-year-old female patient with a microdeletion of chromosome
      1p31.3 who has developmental delay, metopic synostosis and macroscopic
      haemoglobinuria. She was investigated with karyotyping, subtelomeric FISH and
      microarray CGH. RESULTS: Array CGH identified a single 120 kb microdeletion of
      1p31.3 involving exons 4-9 of the NFIA gene. Her brain MRI showed hypoplasia of
      the corpus callosum especially in the posterior areas. Karyotype was normal,
      ruling out structural chromosomal abnormalities. CONCLUSION: In this study, we
      confirmed that a microdeletion in the chromosome region 1p31.3 involving the NFIA
      gene is associated with hypoplasia of the corpus callosum, developmental delay,
      metopic synostosis and urinary tract abnormalities. Furthermore, we propose a
      mechanism by which disruptions in the NFIA gene causes craniofacial
      abnormalities. This report presents the first case of an intragenic deletion
      within the NFIA gene that is still consistent with classic clinical phenotypes
      present in previously reported cases of chromosome 1p31.3 related deletion. This
      finding will help clarify the role of the NFIA gene in the normal formation of
      parts of the CNS, the craniofacial complex and the urinary tract.

PMID- 24462884
TI  - Modification of severe insulin resistant diabetes in response to lifestyle
      changes in Alstrom syndrome.
AB  - BACKGROUND: Alstrom syndrome is a recessively inherited condition characterised
      by severe insulin resistance and metabolic syndrome with progression to type 2
      diabetes, hepatic dysfunction and coronary artery disease. The metabolic
      responses to lifestyle changes in the syndrome have not been reported. CASE
      REPORTS: We describe the effects on glycaemia of intense cycling in two insulin
      treated Alstrom patients with diabetes, and the effects of opposite lifestyle
      changes over one year in two others. METHODS: After practise and clinical
      assessment two patients aged 21 and 39 years undertook a 380 km cycle ride over 4
      days by tandem. The effects of planned reductions in insulin therapies and
      increased regular carbohydrate ingestion were monitored by frequent capillary
      blood glucose measurements. Two siblings aged 22 and 25 years underwent
      assessment of glycaemia, C-peptide/glucose ratio serum lipids, hepatic function
      and ultrasound, Enhanced Liver Fibrosis test and measures of insulin resistance.
      Measurements were repeated one year later after profound lifestyle changes.
      RESULTS: Aerobic exercise strikingly improved blood glucose control despite
      reduction in insulin dose and increased carbohydrate intake. Increase in exercise
      and exclusion of fast foods improved all aspects of the metabolic syndrome and
      induced remission of diabetes in one sibling. Reduction in exercise and
      consumption of high energy foods in the other resulted in development of type 2
      diabetes, severe metabolic syndrome and fatty liver in the other. CONCLUSIONS:
      Despite dual sensory loss and genetic basis for insulin resistance, Alstrom
      patients can successfully ameliorate the metabolic syndrome with lifestyle
      changes.

PMID- 24462885
TI  - Confirmation and further delineation of the 3q26.33-3q27.2 microdeletion
      syndrome.
AB  - Recently, 3 unrelated children with a potentially novel 3q26.33-3q27.2
      microdeletion syndrome were reported. We now report a new 9 1/2 years old
      Caucasian boy with a 2 Mb deletion of the same genomic region in combination with
      Klinefelter syndrome. He presented with facial dysmorphism, developmental delay,
      Asperger syndrome, thrombocytopenia, recurrent infections and
      hypogammaglobulinemia. The deletion in our patient improves upon the minimum
      region of the novel 3q26.33-3q27.2 microdeletion, and provides additional
      insights into the underlying genetic basis of the observed phenotypes. Consistent
      with two of three previously described patients, our patient also presents with
      thrombocytopenia, which we postulate is caused by haploinsufficiency of THPO. In
      addition, haploinsufficiency of LAMP3, a lymphoid and dendritic cell expressed
      protein that is implicated in bacterial and viral infections, pulmonary
      surfactant protein transport and amelogenin degradation, may be a novel cause for
      the immune deficiency, lung disease and dental abnormalities respectively as seen
      in these patients. 

PMID- 24462886
TI  - Clinical assessment of five patients with BRWD3 mutation at Xq21.1 gives further
      evidence for mild to moderate intellectual disability and macrocephaly.
AB  - Truncating mutations of the BRWD3 gene have been reported in two distinct
      families with in total four patients so far. By using array-CGH, we detected a 74
      Kb de novo deletion encompassing exons 11 through 41 of BRWD3 at Xq21.1 in a 20
      year old boy presenting with syndromic intellectual disability. In addition, by
      using exome sequencing, we ascertained a family with a BRWD3 nonsense mutation,
      p.Tyr1131*, in four males with intellectual disability. We compared the clinical
      presentation of these five patients to that of the four patients already
      described in the literature for further delineation of the clinical spectrum in
      BRWD3-related intellectual disability. The main symptoms are mild to moderate
      intellectual disability (n = 9/9) with speech delay (n = 8/8), behavioral
      disturbances (n = 7/8), macrocephaly (n = 7/9), dysmorphic facial features (n =
      9/9) including prominent forehead, pointed chin, deep-set eyes, abnormal ears,
      and broad hands and feet (n = 6/6), and skeletal symptoms (n = 7/7) like pes
      planus, scoliosis, kyphosis and cubitus valgus.

PMID- 24462888
TI  - Fragile X Syndrome: from molecular pathology to therapy.
AB  - Fragile X Syndrome (FXS) is the most common form of inherited intellectual
      disability due to the silencing of the FMR1 gene encoding FMRP (Fragile X Mental
      Retardation Protein), an RNA-binding protein involved in different steps of RNA
      metabolism. Of particular interest is the key role of FMRP in translational
      regulation. Since the first functional characterizations of FMRP, its role has
      been underlined by its association with actively translating polyribosomes.
      Furthermore, a plethora of mRNA targets of FMRP have been identified. In the
      absence of FMRP the deregulation of translation/transport/stability of these
      mRNAs has a cascade effect on many pathways, resulting into the final phenotype.
      We review here a set of targets of FMRP (mRNAs and proteins) that may have an
      impact on the FXS phenotype by deregulating some key cellular processes, such as
      translation, cytoskeleton remodeling and oxidative stress. The manipulation of
      these abnormal pathways by specific drugs may represent new therapeutic
      opportunities for FXS patients. 

PMID- 24462887
TI  - Methylene blue does not reverse existing neurofibrillary tangle pathology in the
      rTg4510 mouse model of tauopathy.
AB  - Alzheimer's disease is characterized pathologically by aggregation of amyloid
      beta into senile plaques and aggregation of pathologically modified tau into
      neurofibrillary tangles. While changes in amyloid processing are strongly
      implicated in disease initiation, the recent failure of amyloid-based therapies
      has highlighted the importance of tau as a therapeutic target. "Tangle busting"
      compounds including methylene blue and analogous molecules are currently being
      evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that
      methylene blue can reverse tau aggregation in vitro after 10 min, and subsequent
      studies suggested that high levels of drug reduce tau protein levels (assessed
      biochemically) in vivo. Here, we tested whether methylene blue could remove
      established neurofibrillary tangles in the rTg4510 model of tauopathy, which
      develops robust tangle pathology. We find that 6 weeks of methylene blue dosing
      in the water from 16 months to 17.5 months of age decreases soluble tau but does
      not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas
      positive tangle pathology. These data indicate that methylene blue treatment will
      likely not rapidly reverse existing tangle pathology.

PMID- 24462889
TI  - Inflammation and the developing brain: consequences for hippocampal neurogenesis
      and behavior.
AB  - While the detrimental impact of inflammation on adult hippocampal neurogenesis
      and associated behaviors has recently gained credence, the effects of
      inflammation on the developing brain is an area of research which is quickly
      gaining momentum, and a growing number of research articles on this topic have
      been published in recent years. Indeed, we now know that pro-inflammatory
      mediators negatively influence both hippocampal neurogenesis and neuronal
      cytoarchitecture during brain development. Here we present a comprehensive review
      of the current literature on inflammation-induced changes in hippocampal
      neurogenesis during early life and the consequent behavioral deficits which may
      ensue in later life. We also offer insights into the cellular and molecular
      mechanisms underlying the hippocampal-dependant behavioral changes observed in
      neurodevelopmental disorders, particularly in those where cognitive dysfunction
      plays a major role. We further consider whether early-life inflammation-induced
      changes in hippocampal neurogenesis may contribute to the onset of mood and
      cognitive deficits in later life. 

PMID- 24462890
TI  - Existence of Cl in municipal solid waste incineration bottom ash and
      dechlorination effect of thermal treatment.
AB  - Municipal solid waste incineration (MSWI) is widely used in Japan, through which
      large amount of incineration residues are produced. The recycle/reuse of the
      incineration residues is troubled by many factors. This paper studied the MSWI
      bottom ash with the principal focus on Cl. Both bulk analysis and microanalysis
      methods have been carried out. The bulk analysis disclosed a particle-size
      dependent pattern of the Cl content in the bottom ash and the insoluble Cl is
      essentially in the form of Friedel's salt (3CaO.Al(2)O(3).CaCl(2).10H(2)O). The
      microanalysis revealed that Cl preferentially exists in the quench phase of the
      individual bottom ash particle. Since Friedel's salt and the other quench
      products are thermally unstable, a series of thermal treatments were carried out
      to decompose such Cl-bearing phases. The experimental results showed the total Cl
      content in the MSWI bottom ash was reduced by 55.46% after a 4-h heating process
      at 1000 degrees C. The removal of the soluble Cl (originally as alkali salts) by
      the thermal process was found to be more effective. However, the insoluble Cl
      content in the heated sample was barely lowered owing to the formation of calcium
      chlorocalumite (11CaO.7Al(2)O(3).CaCl(2)) in the course of heating.

PMID- 24462891
TI  - Preparation, characterization and application of NaHCO3 leached bulk U(VI)
      imprinted polymers endowed with gamma-MPS coated magnetite in contaminated water.
AB  - A new type of ion imprinted polymer (IIP) embedded with gamma
      methacryloxypropyltrimethoxysilane (gamma-MPS) coated magnetic particles for
      selective extraction of uranyl ions was synthesized by bulk polymerization. The
      performance of the magnetic sorbent on the extraction of U(VI) was evaluated by
      various parameters which included the influence of pH, amount of the magnetic
      polymers, contact time and initial U(VI) concentration. The adsorption capacity
      of the magnetic polymers was found to be 1.1 and 0.95mgg(-1) for the IIP and its
      control ion non-imprinted polymer (NIP), respectively. The optimum amount of the
      sorbent was 50mg for an initial concentration of 2.5mgL(-1). The prepared
      magnetic imprinted sorbent displayed an uptake with a time of 45min considered
      optimum. The magnetic polymer displayed good selectivity and exhibited good
      reusability. Studies from binary mixtures of metal ions in aqueous solutions
      showed that the magnetic adsorbent selectivity following the order:
      U(VI)>Ni(II)>Pb(II). Experimental results illustrated the potential application
      of magnetic ion imprinted polymer sorbents for selective removal of U(VI) from
      contaminated water. 

PMID- 24462892
TI  - (18)O(2) label mechanism of sulfur generation and characterization in properties
      over mesoporous Sm-based sorbents for hot coal gas desulfurization.
AB  - Using a sol-gel method, SmMeOx/MCM-41 or SBA-15 (Me=Fe, Co and Zn) and
      corresponding unsupported sorbents were prepared. The desulfurization performance
      of these sorbents was evaluated over a fixed-bed reactor and the effects of
      reaction temperature, feed and sorbent composition on desulfurization performance
      were studied. Samarium-based sorbents used to remove H2S from hot coal gas were
      reported for the first time. The results of successive sulfidation/regeneration
      cycles revealed that SmFeO3/SBA-15 sorbent was suitable for desulfurization of
      hot coal gas in the chemical industry. The formation of elemental sulfur during
      both sulfidation and regeneration processes depended strongly on the catalytic
      action of Sm2O2S species, which was confirmed for the first time via high
      sensitive time of flight mass spectrometer (TOF-MS) using 6%vol(18)O2/Ar
      regeneration gas and can reduce markedly procedural complexity. The sorbents were
      characterized using N2-adsorption, high-resolution transmission electron
      microscopy (HRTEM), X-ray diffraction (XRD), temperature-programmed reduction of
      H2 (H2-TPR), thermogravimetry (TG) and time-of-flight mass spectrometry (TOF-MS)
      techniques. 

PMID- 24462893
TI  - High-performance Ti/Sb-SnO(2)/Pb(3)O(4) electrodes for chlorine evolution:
      preparation and characteristics.
AB  - Chlorine evolution via electrochemical approach has wide application prospects in
      drinking water disinfection and wastewater treatment fields. Dimensional stable
      anodes used for chlorine evolution should have high stability and adequate
      chlorine evolution efficiency. Thus a novel and cost-effective Ti/Sb
      SnO(2)/Pb(3)O(4)electrode was developed. The physicochemical and electrochemical
      properties as well as the chlorine evolution performances of the electrodes were
      investigated. The electrocatalytic activity and deactivation course of the
      electrodes were also explored. Results showed that this novel electrode had
      strong chlorine evolution ability with high current efficiency ranging from 87.3%
      to 93.4% depending on the operational conditions. The accelerated service life of
      Ti/Sb-SnO(2)/Pb(3)O(4) electrode could reach 180 h at a current density of 10,000
      A m(-2) in 0.5 molL(-1) H(2)SO(4). During the electrolysis process, it was found
      that the conversion of Pb(3)O(4) into beta-PbO(2) happened gradually on the
      electrode surface, which not only inhibited the leakage of hazardous Pb(2+) ion
      but also increased the anti-corrosion capacity of the electrode effectively.

PMID- 24462894
TI  - Alternative waste residue materials for passive in situ prevention of sulfide
      mine tailings oxidation: a field evaluation.
AB  - Novel solutions for sulfide-mine tailings remediation were evaluated in field
      scale experiments on a former tailings repository in northern Sweden. Uncovered
      sulfide-tailings were compared to sewage-sludge biosolid amended tailings over 2
      years. An application of a 0.2m single-layer sewage-sludge amendment was
      unsuccessful at preventing oxygen ingress to underlying tailings. It merely
      slowed the sulfide-oxidation rate by 20%. In addition, sludge-derived metals (Cu,
      Ni, Fe, and Zn) migrated and precipitated at the tailings-to-sludge interface. By
      using an additional 0.6m thick fly-ash sealing layer underlying the sewage sludge
      layer, a solution to mitigate oxygen transport to the underlying tailings and
      minimize sulfide-oxidation was found. The fly-ash acted as a hardened physical
      barrier that prevented oxygen diffusion and provided a trap for sludge-borne
      metals. Nevertheless, the biosolid application hampered the application, despite
      the advances in the effectiveness of the fly-ash layer, as sludge-borne nitrate
      leached through the cover system into the underlying tailings, oxidizing pyrite.
      This created a 0.3m deep oxidized zone in 6-years. This study highlights that
      using sewage sludge in unconventional cover systems is not always a practical
      solution for the remediation of sulfide-bearing mine tailings to mitigate against
      sulfide weathering and acid rock drainage formation. 

PMID- 24462895
TI  - Allorecognition of HLA-DP by CD4+ T cells is affected by polymorphism in its
      alpha chain.
AB  - Alloreactivity to HLA-DP molecules, class II heterodimers of an oligomorphic
      alpha and a polymorphic beta chain, is increasingly being studied due to its
      relevance in clinical transplantation. We hypothesized that not only
      polymorphisms in the peptide binding groove encoded by exon 2 of HLA-DPB1, but
      also in other regions of the molecule and the alpha chain, could play a role in
      CD4+ T cell allorecognition. To test this possibility, we comparatively
      investigated CD4+ T cell allorecognition, measured by upregulation of the
      activation marker CD137, against HLA-DPB1*13:01, *05:01, *03:01, *17:01 or their
      allele counter parts DPB1*107:01, *135:01, *104:01, *131:01, with identical exon
      2 sequences but polymorphism in exons 1, 3 or 4, in the context of different HLA
      DPA1 (DPA1) polymorphisms (DPA1*01:03 and *02:01). No significant differences in
      CD4+ T cell allorecognition levels could be demonstrated for any of the beyond
      exon 2 DPB1 variants studied. Interestingly, however, the mean fold change in
      CD4+ CD137+ cells was significantly higher when the target shared at least one
      DPA1 allele with the allogeneic stimulator, compared to a distinct DPA1
      background (1.65 vs 0.23, P<0.005). Structural homology modeling suggested
      specific amino acid residues in the alpha chain, in particular position 31, to
      impact CD4+ T cell allorecognition of HLA-DP. Our data argue against a
      significant role of beyond exon 2 DPB1 polymorphisms for T cell alloreactivity,
      but show relevance of DPA1 polymorphism in this mechanism. These new findings
      impact HLA matching strategies in unrelated stem cell transplantation. 

PMID- 24462896
TI  - Inhibition of IL-2 inducible T-cell kinase alleviates T-cell activation and
      murine myocardial inflammation associated with CVB3 infection.
AB  - BACKGROUND: Coxsackievirus B3 (CVB3) infection causes myocarditis, pancreatitis,
      and aseptic meningitis. Targeting antigen-specific T cell reactions might be a
      promising way to alleviate the inflammatory response induced by CVB3 infection.
      IL-2-inducible T-cell kinase (ITK), a member of Tec kinase family expressed
      mainly in T cells, plays an important role in the activation of T cells. The role
      of ITK in viral myocarditis induced by CVB3 has not been documented. METHODOLOGY:
      In this study, we inhibited the ITK expression in Jurkat cells, primary human
      peripheral blood mononuclear cells (PBMC), and mouse splenocytes by ITK-specific
      siRNA. The inhibition efficiently suppressed cell proliferation (P<0.05) and T
      cell related cytokine secretion (P<0.05). In order to inhibit ITK in vivo, the
      pGCSIL plasmid containing short hairpin RNAs targeting ITK was constructed and
      transduced into mice infected with CVB3. ITK-inhibited mice showed reduced cell
      proliferation (3, 5, and 7 days post-challenge, P<0.05) as well as CD4+ and CD8+
      T cells (5 days post-challenge, P<0.05). The altered production of inflammatory
      cytokines alleviated pathologic heart damage and improved mice survival rate
      (P<0.05). CONCLUSION: ITK played an important role in the T cell development and
      represented a new target for the modulation of T-cell-mediated inflammatory
      response by CVB3 infection.

PMID- 24462897
TI  - Spatial invasion dynamics on random and unstructured meshes: implications for
      heterogeneous tumor populations.
AB  - In this work we discuss a spatial evolutionary model for a heterogeneous cancer
      cell population. We consider the gain-of-function mutations that not only change
      the fitness potential of the mutant phenotypes against normal background cells
      but may also increase the relative motility of the mutant cells. The spatial
      modeling is implemented as a stochastic evolutionary system on a structured grid
      (a lattice, with random neighborhoods, which is not necessarily bi-directional)
      or on a two-dimensional unstructured mesh, i.e. a bi-directional graph with
      random numbers of neighbors. We present a computational approach to investigate
      the fixation probability of mutants in these spatial models. Additionally, we
      examine the effect of the migration potential on the spatial dynamics of mutants
      on unstructured meshes. Our results suggest that the probability of fixation is
      negatively correlated with the width of the distribution of the neighborhood
      size. Also, the fixation probability increases given a migration potential for
      mutants. We find that the fixation probability (of advantaged, disadvantaged and
      neutral mutants) on unstructured meshes is relatively smaller than the
      corresponding results on regular grids. More importantly, in the case of neutral
      mutants the introduction of a migration potential has a critical effect on the
      fixation probability and increases this by orders of magnitude. Further, we
      examine the effect of boundaries and as intuitively expected, the fixation
      probability is smaller on the boundary of regular grids when compared to its
      value in the bulk. Based on these computational results, we speculate on possible
      better therapeutic strategies that may delay tumor progression to some extent. 

PMID- 24462898
TI  - Hydrogel-nanoparticle composites for optically modulated cancer therapeutic
      delivery.
AB  - A poly(N-isopropylacrylamide-co-acrylamide) (NIPAAm-co-AAm) hydrogel with near
      infrared (NIR) absorbing silica-gold nanoshells was designed as a platform for
      pulsatile delivery of cancer therapeutics. This hydrogel was designed to have a
      lower critical solution temperature (LCST) above physiologic temperature, such
      that the material will transition from a hydrated state to a collapsed state
      above ~40 degrees C. Additionally, the silica-gold nanoshells used were designed
      to have a peak extinction coefficient in the NIR, where penetration of light
      through tissue is maximal. This heat-triggered material phase transition of the
      composite was found to follow exposure of NIR light, indicating the ability of
      the NIR absorption by the nanoshells to sufficiently drive this transition. The
      composite material was loaded with either doxorubicin or a DNA duplex (a model
      nucleic acid therapeutic), two cancer therapeutics with differing physical and
      chemical properties. Release of both therapeutics was dramatically enhanced by
      NIR light exposure, causing 2-5x increase in drug release. Drug delivery profiles
      were influenced by both the molecular size of the drug as well as its chemical
      properties. The DNA therapeutic showed slower rates of nonspecific delivery by
      passive diffusion due to its larger size. Additionally, only 70% of the more
      hydrophobic doxorubicin was released from the material, whereas the more
      hydrophilic DNA showed over 90% release. Further, hydrogel composites were used
      to deliver the doxorubicin to CT.26-WT colon carcinoma cells, eliciting a
      therapeutic response. This work validates the potential application for this
      material in site-specific cancer therapeutic delivery. 

PMID- 24462899
TI  - Synthesis and therapeutic evaluation of an aptide-docetaxel conjugate targeting
      tumor-associated fibronectin.
AB  - Targeted delivery of anticancer drugs to tumors has attracted considerable
      research interest because of its potential to reduce adverse toxicity while
      improving therapeutic efficacy. In this study, we synthesized and evaluated the
      therapeutic efficacy of a conjugate of a high-affinity peptide (aptide) and the
      anticancer drug docetaxel (DTX). A fibronectin extra domain B (EDB)-specific
      aptide (APTEDB) was used as a cancer-specific targeting ligand. An APTEDB-DTX
      conjugate was synthesized from an alkyne-modified aptide and azide-modified DTX
      via click chemistry. A microscopy study revealed selective binding of dye-labeled
      APTEDB to EDB-overexpressing cancer cells. The cytotoxicity of the conjugate
      toward EDB-overexpressing murine lung carcinoma (LLC) and human glioblastoma
      (U87MG) was similar to that of free DTX. In a pharmacokinetic study, APTEDB-DTX
      formulated with PEG400/ethanol(5%) exhibited a circulation half-life similar to
      that of a Tween-80/ethanol formulation of parent DTX. Finally, an evaluation of
      intravenously injected APTEDB-DTX in mice bearing EDB-positive tumors showed that
      APTEDB-DTX inhibited the growth of both LLC allograft and U87MG xenograft tumors
      with an efficacy better than the parent-DTX formulation but with much lower
      toxicity, as evidenced by reduced body weight loss. Taken together, these results
      indicate that the aptide-drug conjugate system described here may hold potential
      as a targeted therapy regimen. 

PMID- 24462900
TI  - Polyplex-releasing microneedles for enhanced cutaneous delivery of DNA vaccine.
AB  - Microneedle (MN)-based DNA vaccines have many advantages over conventional
      vaccines administered by hypodermic needles. However, an efficient strategy for
      delivering DNA vaccines to intradermal cells has not yet been established. Here,
      we report a new approach for delivering polyplex-based DNA vaccines using MN
      arrays coated with a pH-responsive polyelectrolyte multilayer assembly (PMA).
      This approach enabled rapid release of polyplex upon application to the skin. In
      addition to the polyplex-releasing MNs, we attempted to further maximize the
      vaccination by developing a polymeric carrier that targeted resident antigen
      presenting cells (APCs) rich in the intradermal area, as well as a DNA vaccine
      encoding a secretable fusion protein containing amyloid beta monomer (Abeta1-42),
      an antigenic determinant. The resulting vaccination system was able to
      successfully induce a robust humoral immune response compared to conventional
      subcutaneous injection with hypodermal needles. In addition, antigen challenge
      after immunization elicited an immediate and strong recall immune response due to
      immunogenic memory. These results suggest the potential utility of MN-based
      polyplex delivery systems for enhanced DNA vaccination. 

PMID- 24462901
TI  - Tumor priming enhances siRNA delivery and transfection in intraperitoneal tumors.
AB  - Cancers originating from the digestive system account for 290,000 or ~20% of all
      new cancer cases annually in the US. We previously developed paclitaxel-loaded
      tumor-penetrating microparticles (TPM) for intraperitoneal (IP) treatment of
      peritoneal tumors (Lu et al., 2008; Tsai et al., 2007; Tsai et al., 2013). TPM is
      undergoing NIH-supported IND-enabling studies for clinical evaluation. The
      present study evaluated the hypothesis that TPM, via inducing apoptosis and
      expanding the interstitial space, promotes the delivery and transfection of lipid
      vectors containing siRNA. The in vivo model was the metastatic human Hs766T
      pancreatic tumor that, upon IP injection, produced widely distributed solid
      tumors and ascites in the peritoneal cavity in 100% of animals. The target gene
      was survivin, an anti-apoptotic protein induced by chemotherapy and associated
      with metastases and poor prognosis of patients with gastric and colorectal
      cancers. The siRNA carrier was pegylated liposomes comprising cationic and
      neutral lipids plus a fusogenic lipid (PCat). PCat-loaded with survivin siRNA
      (PCat-siSurvivin) was active in cultured cells (decreased survivin mRNA and
      protein levels, reduced cell clonogenicity, enhanced paclitaxel activity), but
      lost its activity in vivo; this difference is consistent with the well-known
      problem of inadequate delivery and transfection of siRNA in vivo. In comparison,
      single agent TPM prolonged animal survival and, as expected, induced survivin
      expression in tumors. Addition of PCat-siSurvivin reversed the TPM-induced
      survivin expression and enhanced the antitumor activity of TPM. The finding that
      in vivo survivin knockdown by PCat-siSurvivin was successful only when it was
      given in combination with TPM provides the proof-of-concept that tumor priming
      promotes the delivery and transfection of liposomal siRNA. The data further
      suggest the TPM/PCat-siSurvivin combination as a potentially useful chemo-gene
      therapy for peritoneal cancer. 

PMID- 24462902
TI  - Cell division responsive peptides for optimized plasmid DNA delivery: the mitotic
      window of opportunity?
AB  - The delivery of plasmid DNA remains hard to achieve, especially due to the
      presence of the nuclear membrane barrier. During cell division, however, the
      nuclear membrane is temporarily disassembled. We evaluated two different
      strategies to optimize plasmid DNA delivery in dividing cells: 1) phosphorylation
      responsive peptides that release plasmid DNA preferentially during mitosis and 2)
      chromatin targeting peptides to anchor plasmid DNA in newly formed nuclei upon
      cell division. Peptide/DNA particles alone were not efficient in penetrating
      cells. Upon co-delivery with lipid-based carriers, however, transfection
      efficiency drastically improved when compared to controls. For the
      phosphorylation responsive peptides, the presence of the phosphorylation sequence
      slightly increased transfection efficiency. For the chromatin targeting peptides,
      however, the chromatin targeting sequence did not seem to be the main reason for
      the improvement of transfection efficiency when applied in living cells. In
      conclusion, the pre-condensation of plasmid DNA with peptides improves lipid
      based delivery, but the nature of the peptides (cell responsive or not) does not
      seem to be the main reason for the improvement. It seems that the nuclear entry
      of foreign plasmid DNA is still under tight control, even during the mitotic
      window of opportunity. 

PMID- 24462905
TI  - Diverse inter-continental and host lineage reassortant avian influenza A viruses
      in pelagic seabirds.
AB  - Avian influenza A viruses (AIVs) often infect waterfowl, gulls and shorebirds,
      but other bird groups including pelagic seabirds also serve as hosts. In this
      study, we analyzed 21 AIVs found in two distant breeding colonies of Common Murre
      (Uria aalge) in Newfoundland and Labrador, Canada, during 2011. Phylogenetic
      analyses and genotype assignments were performed for the 21 Common Murre viruses
      together with all Common and Thick-billed Murre (Uria lomvia) AIV sequences
      available in public sequence databases. All fully characterized viruses from the
      Common Murres in 2011 were H1N2 subtype, but the genome sequences revealed
      greater diversity and the viruses belonged to four distinct genotypes. The four
      genotypes shared most segments in common, but reassortment was observed for PB2
      and M segments. This provided direct genetic data of AIV diversification through
      segment reassortment during an outbreak of AIV infection in high-density breeding
      colonies. Analysis of the total collection of available murre viruses revealed a
      diverse collection of subtypes and gene lineages with high similarity to those
      found in viruses from waterfowl and gulls, and there was no indication of murre
      specific AIV gene lineages. Overall, the virus gene pool in murres was
      predominantly made up of AIV lineages associated with waterfowl, but also
      featured considerable gull lineage genes and inter-continental reassortments. In
      particular, all but one of the 21 Common Murre viruses from 2011 in Newfoundland
      contained 1 or 2 Eurasian segments and 16 contained 1 gull lineage segment. This
      mosaic nature of characterized murre AIV genomes might reflect an under
      recognized role of these pelagic seabirds in virus transmission across space and
      between bird host taxa. 

PMID- 24462903
TI  - Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body
      disease.
AB  - Considerable progress has been made in the past few years in the fight against
      Alzheimer's disease (AD) and Parkinson's disease (PD). Neuropathological studies
      in human brains and experimental in vivo and in vitro models support the notion
      that synapses are affected even at the earliest stages of the neurodegenerative
      process. The objective of this manuscript is to review some of the mechanisms of
      synaptic damage in AD and PD. Some lines of evidence support the notion that
      oligomeric neurotoxic species of amyloid beta, alpha-synuclein, and Tau might
      contribute to the pathogenesis of synaptic failure at early stages of the
      diseases. The mechanisms leading to synaptic damage by oligomers might involve
      dysregulation of glutamate receptors and scaffold molecules that results in
      alterations in the axonal transport of synaptic vesicles and mitochondria that
      later on lead to dendritic and spine alterations, axonal dystrophy, and
      eventually neuronal loss. However, while some studies support a role of
      oligomers, there is an ongoing debate as to the exact nature of the toxic
      species. Given the efforts toward earlier clinical and preclinical diagnosis of
      these disorders, understanding the molecular and cellular mechanisms of synaptic
      degeneration is crucial toward developing specific biomarkers and new therapies
      targeting the synaptic apparatus of vulnerable neurons. 

PMID- 24462906
TI  - Limited genetic diversity and purifying selection in Iranian Plasmodium
      falciparum Generative Cell Specific 1 (PfGCS1), a potential target for
      transmission-blocking vaccine.
AB  - Among vaccines, those that have an impact on transmission are in priority for
      malaria elimination and eradication. One of the new identified transmission
      blocking vaccine (TBV) candidate antigens is Generative Cell Specific 1 (GCS1)
      located on the male gametocytes of Plasmodium species. Since the antigenic
      diversity could hamper vaccine development, it is essential to determine the gene
      diversity of gcs1 in global malaria-endemic areas in order to develop efficient
      TBVs. Therefore, in this study, nucleotide diversity and selection in the
      Plasmodium falciparum GCS1 (PfGCS1) antigen were analyzed in 36 Iranian clinical
      isolates by using PCR sequencing in order to provide useful information on this
      TBV candidate antigen. For this purpose, successful sequence analysis was carried
      out in 36 isolates. The results showed three single-nucleotide polymorphisms
      including one synonymous (G1475A) and two non-synonymous (A697G and G1479A)
      mutations leading to 3 distinct haplotypes with different frequencies: GCS1-A
      (N184/D445, 16.7%), GCS1-B (S184/D445, 63.9%), and GCS1-C (N184/N445, 19.4%). The
      overall nucleotide diversity (pi) for all 36 sequences of Iranian pfgcs1 was
      0.00066+/-0.00012, and the dN-dS value (-0.00028) was negative, suggesting the
      possible action of purifying selection in this gene. Epitope mapping prediction
      of PfGCS1 antigen showed that most of the potential linear and conformational B
      cell epitopes are located in conserved regions. However, N184S and D445N
      mutations were also involved in linear and conformational B-cell epitopes,
      respectively that should be considered in vaccine design. In conclusion, the
      present study showed a very low genetic diversity of pfgcs1 gene among Iranian
      isolates. Considering PfGCS1 as a conserved TBV candidate, our data provides
      valuable information to develop a PfGCS1-based TBV. 

PMID- 24462907
TI  - Novel circular DNA viruses identified in Procordulia grayi and Xanthocnemis
      zealandica larvae using metagenomic approaches.
AB  - Recent advances in sequencing and metagenomics have enabled the discovery of many
      novel single stranded DNA (ssDNA) viruses from various environments. We have
      previously demonstrated that adult dragonflies, as predatory insects, are useful
      indicators of ssDNA viruses in terrestrial ecosystems. Here we recover and
      characterise 13 viral genomes which represent 10 novel and diverse circular
      replication associated protein (Rep)-encoding single stranded (CRESS) DNA viruses
      (1628-2668nt) from Procordulia grayi and Xanthocnemis zealandica dragonfly larvae
      collected from four high-country lakes in the South Island of New Zealand. The
      dragonfly larvae associated CRESS DNA viruses have different genome
      architectures, however, they all encode two major open reading frames (ORFs)
      which either have bidirectional or unidirectional arrangement. The 13 viral
      genomes have a conserved NAGTATTAC nonanucleotide motif and in their predicted
      Rep proteins we identified the rolling circle replication (RCR) motif 1, 2 and 3,
      as well as superfamily 3 (SF3) helicase motifs. Maximum likelihood phylogenetic
      and pairwise identity analysis of the Rep amino acid sequences reveal that the
      dragonfly larvae novel CRESS DNA viruses share <63% pairwise amino acid identity
      to the Reps of other CRESS DNA viruses whose complete genomes have been
      determined and available in public databases and that these viruses are novel.
      CRESS DNA viruses are circulating in larval dragonfly populations; however, we
      are unable to ascertain whether these viruses are infecting the larvae directly
      or are transient within dragonflies via their diet. 

PMID- 24462908
TI  - Therapeutic vaccines against hepatitis C virus.
AB  - Hepatitis C virus (HCV) is a blood-borne pathogen which has chronically infected
      about 130-210 million people worldwide. Current standard-of-care (SoC) therapy is
      an inadequate and expensive treatment with more side effects. Two direct-acting
      antiviral agents (DAAs) (telaprevir and boceprevir) in combination with SoC
      therapy have been used in patients infected with HCV genotype 1. Although these
      drugs result in a shortening of therapy, they also have additional side effects
      and are expensive. In their stead, several second-generation DAAs are being
      investigated. What important is that all-oral, interferon (IFN)- and ribavirin
      free regimens for the treatment of HCV-infected patients are now being
      investigated, and will be applied in the next year. Preventive measures against
      HCV, including vaccine development, are also now in progress. However, no
      therapeutic vaccine against HCV has been produced to date. An effective vaccine
      should induce robust and broadly cross-reactive CD4(+), CD8(+)T-cell and
      neutralising antibody (NAb) responses. Current data indicate that vaccines can
      usually not completely prevent HCV infection but rather prevent the progression
      of HCV infection to chronic and persistent infection, which may be a realistic
      goal. This review discusses the important roles of NAbs and CD8(+)T-cells in the
      development of therapeutic vaccines, and summarizes some important epitopes of
      HCV recognized by CD8(+)T-cells and some prospective therapeutic vaccine
      approaches. 

PMID- 24462909
TI  - Dynamics in genome evolution of Vibrio cholerae.
AB  - Vibrio cholerae, the etiological agent of the acute secretary diarrheal disease
      cholera, is still a major public health concern in developing countries. In
      former centuries cholera was a permanent threat even to the highly developed
      populations of Europe, North America, and the northern part of Asia. Extensive
      studies on the cholera bug over more than a century have made significant
      advances in our understanding of the disease and ways of treating patients. V.
      cholerae has more than 200 serogroups, but only few serogroups have caused
      disease on a worldwide scale. Until the present, the evolutionary relationship of
      these pandemic causing serogroups was not clear. In the last decades, we have
      witnessed a shift involving genetically and phenotypically varied pandemic clones
      of V. cholerae in Asia and Africa. The exponential knowledge on the genome of
      several representatives V. cholerae strains has been used to identify and analyze
      the key determinants for rapid evolution of cholera pathogen. Recent comparative
      genomic studies have identified the presence of various integrative mobile
      genetic elements (IMGEs) in V. cholerae genome, which can be used as a marker of
      differentiation of all seventh pandemic clones with very similar core genome.
      This review attempts to bring together some of the important researches in recent
      times that have contributed towards understanding the genetics, epidemiology and
      evolution of toxigenic V. cholerae strains. 

PMID- 24462910
TI  - Molecular characterization, tissue distribution, and expression of two ovarian
      Dicer isoforms during follicle development in goose (Anser cygnoides).
AB  - Dicer plays a key role in the biogenesis of microRNAs and small interfering RNAs,
      which control the coordinated expression of multiple of genes during follicle
      development. In this study, the cDNAs encoding two Dicer isoforms (gDicer-a and
      gDicer-b, respectively) were isolated and cloned from goose ovary using RT-PCR.
      This is the first time a new Dicer splice variant has been characterized at the
      molecular level in vertebrates. Sequence analysis indicated that both of the two
      isoforms consist of seven conserved functional domains, where gDicer-b lacks a
      linker sequence between DEAD box and helicase C domain composed of 158 amino
      acids. Each domain of gDicer-a/gDicer-b showed higher than 89.5% identity to
      corresponding domain of Dicers from chicken, human, and mouse. The ubiquity of
      transcripts of gDicer-a/gDicer-b was found in all tested tissues by real time PCR
      with the pituitary, oviduct, and hypothalamus being the predominant site of
      expression of gDicer-a. A similar expression profile of the gDicer-a/gDicer-b
      mRNAs was found during follicle development. The abrupt changes in transcripts of
      gDicer in 2-4mm, 9-10mm, F5, and F1 follicles support its participation in the
      process of follicle recruitment, selection, dominance, and ovulation. However,
      high mRNA levels of gDicer-b and caspase-3 were detectable in atretic and post
      ovulatory follicles, where expression of gDicer-a was considerably low. These
      findings suggest that gDicer is required for follicle development, and structural
      differences in the helicase domain of two gDicer isoforms might contribute to
      their different roles in controlling granulosa cell apoptosis. 

PMID- 24462911
TI  - Effect of fishmeal replacement by soy protein concentrate with taurine
      supplementation on hepatic intermediary metabolism and antioxidant status of
      totoaba juveniles (Totoaba macdonaldi).
AB  - The effect of dietary incorporation of soy protein concentrate (SPC) and the
      concomitant supplementation with taurine on hepatic intermediary metabolism and
      antioxidant status of totoaba (Totoaba macdonaldi) juveniles was assessed. Four
      isoproteic and isolipidic diets were formulated containing either 30 or 60% of
      SPC (diets SP30 and SP60), supplemented or not with 1% of taurine (diets SP30T
      and SP60T). A fish meal (FM) based diet, without SPC and taurine supplementation,
      was used as a control. Triplicate groups of 32 totoaba juveniles (average body
      mass=7.5g) were fed these diets over 45days. Results revealed that dietary FM
      replacement by SPC depressed the overall intermediary metabolism. Activity of key
      enzymes of amino acid catabolism and gluconeogenesis was significantly reduced
      and a trend to reduce glycolysis and glucose-6-phosphate dehydrogenase activity
      was observed. The incorporation of the highest level of SPC also significantly
      increased hepatic lipid peroxidation and the activity of superoxide dismutase.
      Concomitant taurine supplementation restored the activity of amino acid catabolic
      and gluconeogenic enzymes and hexokinase to levels similar of those of the
      control diet. Taurine supplementation also led to a significant increase of
      glucose-6-phosphate dehydrogenase and catalase activity, as well as to a
      significant reduction of liver lipid peroxidation. These results suggest that
      taurine may play an important metabolic modulation action on totoaba fed SPC
      based diets, contributing to the enhancement of the overall metabolism and to the
      reduction of liver oxidative damage. 

PMID- 24462904
TI  - Behavioral assays with mouse models of Alzheimer's disease: practical
      considerations and guidelines.
AB  - In Alzheimer's disease (AD) basic research and drug discovery, mouse models are
      essential resources for uncovering biological mechanisms, validating molecular
      targets and screening potential compounds. Both transgenic and non-genetically
      modified mouse models enable access to different types of AD-like pathology in
      vivo. Although there is a wealth of genetic and biochemical studies on proposed
      AD pathogenic pathways, as a disease that centrally features cognitive failure,
      the ultimate readout for any interventions should be measures of learning and
      memory. This is particularly important given the lack of knowledge on disease
      etiology - assessment by cognitive assays offers the advantage of targeting
      relevant memory systems without requiring assumptions about pathogenesis. A
      multitude of behavioral assays are available for assessing cognitive functioning
      in mouse models, including ones specific for hippocampal-dependent learning and
      memory. Here we review the basics of available transgenic and non-transgenic AD
      mouse models and detail three well-established behavioral tasks commonly used for
      testing hippocampal-dependent cognition in mice - contextual fear conditioning,
      radial arm water maze and Morris water maze. In particular, we discuss the
      practical considerations, requirements and caveats of these behavioral testing
      paradigms. 

PMID- 24462912
TI  - The second type of transglutaminase regulates immune and stress responses in
      white shrimp, Litopenaeus vannamei.
AB  - The total haemocyte count (THC), differential haemocyte count (DHC),
      phenoloxidase activity, respiratory bursts (release of superoxide anion),
      superoxide dismutase activity, and phagocytic activity and clearance efficiency
      to the pathogen Vibrio alginolyticus were measured when white shrimp, Litopenaeus
      vannamei, (7.5 +/- 0.5 g) were individually injected with diethyl pyrocarbonate
      water (DEPC-H2O) or different dsRNA at 3 days of injection. In addition,
      haemolymph glucose and lactate, and haemocytes crustacean hyperglycemic hormone
      (CHH), transglutaminase I (TGI), transglutaminase II (TGII) and clottable protein
      (CP) mRNA expression were determined for the shrimp that received DEPC-H2O and
      different dsRNA after 3 days, and then transferred to 22 and 28  degrees C from
      28  degrees C. Results showed that respiratory burst, phagocytic activity and
      clearance efficiency significantly decreased, but hyaline cells significantly
      increased in the shrimp received LvTGII dsRNA after 3 days. In hypothermal stress
      studies, LvTGI and CHH were significantly up-regulated in LvTGII-depleted shrimp
      following exposure to 28 and 22  degrees C, and haemolymph glucose and lactate
      were significantly enhanced in LvTGII-depleted shrimp. The injection of LvTGII
      dsRNA also significantly increased the mortality of L. vannamei challenged with
      the pathogen V. alginolyticus. These results suggest that LvTGII is an important
      component on the immune resistance of shrimp, and is involved in the regulation
      of some immune parameters and carbohydrate metabolites, as well as has a
      complementary effect with LvTGI in immunological and physiological response of
      shrimp. 

PMID- 24462913
TI  - What is the real significance and management of major thyroid disorders in
      bipolar patients?
AB  - Thyroid disfunction affects negatively emotional stability and worsens the
      clinical course of bipolar affective disorder. The main stabilizer used in this
      illness, lithium carbonate has numerous effects on the physiology of the thyroid,
      with the most significant being the inhibition of thyroid hormone release that
      may occur at therapeutic levels. These dysfunctions have also been reported most
      frequently in bipolar patients not undergoing treatment with lithium, and was not
      completely explained by the effects of this drug. Apart from the numerous medical
      complications and mood disturbances, the cognitive or perceptual system may also
      be affected. In fact, the presence of thyroid disease increases the rates of
      obsessive compulsive disorder, phobias, panic disorder, major depressive
      disorder, cyclothymia, or bipolar disorder. In severe cases of hypothyroidism,
      the clinical symptoms and signs can be similar to a melancholic depression or
      dementia. It is therefore important to know well all these possible complications
      in daily clinical practice. This review will cover the main thyroid dysfunctions
      present in bipolar patients, whether ot not produced by treatment with lithium
      carbonate, and will provide a series of recommendations for clinical management. 

PMID- 24462914
TI  - Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of
      glucolipotoxicity and diabetes.
AB  - Increased intracellular generation of reactive oxygen species [ROS] has been
      implicated in the pathology of metabolic [diabetes] and neurodegenerative
      [Alzheimer's] diseases. Accumulating evidence suggests NADPH oxidases [Noxs] as
      the principal source for cellular ROS in humans. Of this class of enzymes, the
      phagocyte-like Nox [Nox2] has come under intense scrutiny as one of the
      "culprits" for the induction of cellular damage culminating in the onset of
      diabetes and its complications. Functional regulation of Nox2 is fairly complex
      due to its membranous [gp91(phox), p22(phox)] and cytosolic [p40(phox),
      p47(phox), p67(phox) and Rac1] cores, which require specific post-translational
      modification steps [phosphorylation and lipidation] for their membrane
      association. Therefore, optimal efficacy of Nox2 depends upon precise regulation
      of these signaling steps followed by translocation of the cytosolic components to
      the membrane. Interestingly, numerous recent studies have reported sustained
      activation of Nox2, ROS-derived oxidative stress, and cellular dysfunction in in
      vitro and in vivo models of glucolipotoxicity and diabetes. These investigations
      employed a variety of cell-permeable peptides and pharmacological inhibitors to
      impede Nox2 holoenzyme assembly and activation in pancreatic islet beta-cells,
      cardiomyocytes and retinal endothelial cells under conditions of
      glucolipotoxicity and diabetes. Herein, we highlight the existing evidence to
      implicate Nox2 as the "trigger" of cellular damage, and identify critical gaps in
      our current understanding that need to be addressed to further affirm the roles
      of Nox2 as a potential therapeutic target for the treatment of diabetes and other
      metabolic disorders.

PMID- 24462915
TI  - Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on
      glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an
      in vivo rat model.
AB  - Cyclosporin A (CsA) and sirolimus (SRL) are immunosuppressive agents (IAs)
      associated with dyslipidemia, insulin resistance and new onset diabetes after
      transplantation (NODAT). However, the molecular mechanisms involved are not fully
      understood. We investigated the effects of six-week treatment of either CsA or
      SRL on glucose and lipid metabolism in Wistar rats. The results show that,
      compared with vehicle-treated rats, SRL-treated rats were significantly lighter
      starting at week 5. CsA or SRL caused glucose intolerance, increased storage of
      lipids in the liver and skeletal muscle, and decreased the insulin-stimulated
      glucose uptake in isolated adipocytes. Furthermore, these agents significantly
      decreased genes involved in insulin action and glucose uptake, such as, IRS-1,
      Glut4 and Glut1, and increased genes and/or proteins involved in hepatic
      lipogenesis and gluconeogenesis, while decreasing them in adipose tissue. After
      either treatment PGC1alpha gene expression was down regulated in skeletal muscle,
      an important player in fatty acid oxidation. Moreover, there was an increase in
      IL-6 gene expression in adipose tissue in the SRL-treated rats, suggesting
      stimulation of lipolysis. The results of the present study suggest that CsA and
      SRL lead to metabolic alterations in liver, muscle and adipose tissue, which may
      contribute to the development of dyslipidemia and insulin resistance associated
      with immunosuppressive therapy. 

PMID- 24462916
TI  - Paris saponin VII inhibits growth of colorectal cancer cells through Ras
      signaling pathway.
AB  - Dysregulation of the Ras signaling pathway plays a key role in the progression of
      colorectal cancer. When bound to GTP, Ras is activated and stimulates several
      downstream effectors' pathways, including the Raf/MEK/ERK kinase cascade, the PI3
      kinase/AKT/mTor pathway, and the Ral GTPase pathway. Saponins extracted from
      Liliaceae family herbs have strong antitumor activities with low toxicity. In
      this study, Paris saponin VII (PSVII), isolated from Trillium tschonoskii Maxim.,
      was evaluated on human colorectal cancer cells (HT-29 and SW-620), a mouse model
      of colitis associated colorectal cancer (CACC) and a murine model of xenograft
      tumor. It was found that PSVII inhibited colorectal cancer cell growth in a
      concentration-dependent manner. The IC50 values of PSVII for growth inhibition of
      HT-29 and SW-620 cells were 1.02 +/- 0.05 MUM and 4.90 +/- 0.23 MUM. It could
      induce cell apoptosis, together with cell cycle arrest in G1 phase, and trigger
      apoptosis in a caspase-3-dependent manner. PSVII-induced growth inhibitory effect
      was associated with disturbance of MAPK pathway by down-regulating MEK1/2, ERK1/2
      phosphorylation, and suppression of AKT pathway by reducing AKT and GSK-3beta
      phosphorylation. In the CACC mouse model, PSVII protected mice from intestinal
      toxicities and carcinogenesis induced by 1,2-dimethylhydrazine (DMH) and dextran
      sodium sulfate (DSS). In the model of xenograft tumor, PSVII remarkably decreased
      the xenograft tumor size and triggered the apoptosis of tumor cells. Both in
      vitro and in vivo study showed that PSVII inhibited Ras activity. Taken together,
      PSVII might be a potential therapeutic reagent for colorectal cancer through
      targeting Ras signaling pathway.

PMID- 24462917
TI  - Activation of PI3K/Akt signaling in rostral ventrolateral medulla impairs brain
      stem cardiovascular regulation that underpins circulatory depression during
      mevinphos intoxication.
AB  - As the most widely used pesticides in the globe, the organophosphate compounds
      are understandably linked with the highest incidence of suicidal poisoning.
      Whereas the elicited toxicity is often associated with circulatory depression,
      the underlying mechanisms require further delineation. Employing the pesticide
      mevinphos as our experimental tool, we evaluated the hypothesis that
      transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-kappaB on
      activation of the PI3K/Akt cascade in the rostral ventrolateral medulla (RVLM),
      the brain stem site that maintains blood pressure and sympathetic vasomotor tone,
      underpins the circulatory depressive effects of organophosphate poisons.
      Microinjection of mevinphos (10 nmol) bilaterally into the RVLM of anesthetized
      Sprague-Dawley rats induced a progressive hypotension that was accompanied
      sequentially by an increase (Phase I) and a decrease (Phase II) of an
      experimental index for the baroreflex-mediated sympathetic vasomotor tone. There
      were also progressive augmentations in PI3K or Akt enzyme activity and
      phosphorylation of p85 or Akt(Thr308) subunit in the RVLM that were causally
      related to an increase in NF-kappaB transcription activity and elevation in NOS
      II or peroxynitrite expression. Loss-of-function manipulations of PI3K or Akt in
      the RVLM significantly antagonized the reduced baroreflex-mediated sympathetic
      vasomotor tone and hypotension during Phase II mevinphos intoxication, and
      blunted the increase in NF-kappaB/NOS II/peroxynitrite signaling. We conclude
      that activation of the PI3K/Akt cascade, leading to upregulation of NF-kappaB/NOS
      II/peroxynitrite signaling in the RVLM, elicits impairment of brain stem
      cardiovascular regulation that underpins circulatory depression during mevinphos
      intoxication.

PMID- 24462918
TI  - Vasopressor meets vasodepressor: The AT1-B2 receptor heterodimer.
AB  - The AT1 receptor for the vasopressor angiotensin II is one of the most important
      drug targets for the treatment of cardiovascular diseases. Sensitization of the
      AT1 receptor system is a common feature contributing to the pathogenesis of many
      cardiovascular disorders but underlying mechanisms are not fully understood. More
      than a decade ago, evidence was provided for control of AT1R activation by
      heterodimerization with the B2 receptor for the vasodepressor peptide,
      bradykinin, a physiological counterpart of the vasoconstrictor angiotensin II.
      AT1-B2 receptor heterodimerization was shown to enhance AT1R-stimulated signaling
      under pathophysiological conditions such as experimental and human pregnancy
      hypertension. Notably, AT1R signal sensitization of patients with preeclampsia
      hypertension was attributed to AT1R-B2R heterodimerization. Vice versa,
      transgenic mice lacking the AT1-B2 receptor heterodimer due to targeted deletion
      of the B2R gene showed a significantly reduced AT1R-stimulated vasopressor
      response compared to transgenic mice with abundant AT1R-B2R heterodimerization.
      Biophysical methods such as BRET and FRET confirmed those data by demonstrating
      efficient AT1-B2 receptor heterodimerization in transfected cells and transgenic
      mice. Recently, a study on AT1R-specific biased agonism directed the focus to the
      AT1-B2 receptor heterodimer again. The beta-arrestin-biased [Sar1,Ile4,Ile8]
      angiotensin II promoted not only the recruitment of beta-arrestin to the AT1R but
      also stimulated the down-regulation of the AT1R-associated B2 receptor by co
      internalization. Thereby specific targeting of the AT1R-B2R heterodimer became
      feasible and could open the way to a new class of drugs, which specifically
      interfere with pathological angiotensin II-AT1 receptor system activation.

PMID- 24462919
TI  - New perspectives on the role of tau in Alzheimer's disease. Implications for
      therapy.
AB  - Alzheimer's disease (AD) and related dementias constitute a major public health
      issue due to an increasingly aged population as a consequence of generally
      improved medical care and demographic changes. Current drug treatment of AD, the
      most prevalent dementia, with cholinesterase inhibitors or NMDA antagonists have
      demonstrated very modest, symptomatic efficacy, leaving an unmet medical need for
      new, more effective therapies. While drug development efforts in the last two
      decades have primarily focused on the amyloid cascade hypothesis, so far with
      disappointing results, tau-based strategies have received little attention until
      recently despite that the presence of extensive tau pathology is central to the
      disease. The discovery of mutations within the tau gene that cause fronto
      temporal dementia demonstrated that tau dysfunction, in the absence of amyloid
      pathology, was sufficient to cause neuronal loss and clinical dementia. Abnormal
      levels and hyperphosphorylation of tau protein have been reported to be the
      underlying cause of a group of neurodegenerative disorders collectively known as
      'tauopathies'. The detrimental consequence is the loss of affinity between this
      protein and the microtubules, increased production of fibrillary aggregates and
      the accumulation of insoluble intracellular neurofibrillary tangles. However, it
      has become clear in recent years that tau is not only a microtubule interacting
      protein, but rather has additional roles in cellular processes. This review
      focuses on emerging therapeutic strategies aimed at treating the underlying
      causes of the tau pathology in tauopathies and AD, including some novel
      approaches on the verge of providing new treatment paradigms within the coming
      years. 

PMID- 24462921
TI  - Associations between weather conditions and clinical symptoms in patients with
      hip osteoarthritis: a 2-year cohort study.
AB  - The goal of this study was to assess whether there is an association between
      ambient weather conditions and patients' clinical symptoms in patients with hip
      osteoarthritis (OA). The design was a cohort study with a 2-year follow-up and 3
      monthly measurements and prospectively collected data on weather variables. The
      study population consisted of 222 primary care patients with hip OA. Weather
      variables included temperature, wind speed, total amount of sun hours,
      precipitation, barometric pressure, and relative humidity. The primary outcomes
      were severity of hip pain and hip disability as measured with the Western Ontario
      and McMasters University Osteoarthritis Index (WOMAC) pain and function
      subscales. Associations between hip pain and hip disability and the weather
      variables were assessed using crude and multivariate adjusted linear mixed-model
      analysis for repeated measurements. On the day of questionnaire completion, mean
      relative humidity was associated with WOMAC pain (estimate 0.1; 95% confidence
      interval=0.0-0.2; P=.02). Relative humidity contributed < or = 1% to the
      explained within-patient variance and between-patient variance of the WOMAC pain
      score. Mean barometric pressure was associated with WOMAC function (estimate 0.1;
      95% confidence interval=0.0-0.1; P=.02). Barometric pressure contributed < or =
      1% to the explained within-patient variance and between-patient variance of the
      WOMAC function score. The other weather variables were not associated with the
      WOMAC pain or function score. Our results support the general opinion of OA
      patients that barometric pressure and relative humidity influence perceived OA
      symptoms. However, the contribution of these weather variables (< or = 1%) to the
      severity of OA symptoms is not considered to be clinically relevant.

PMID- 24462920
TI  - The multikinase inhibitor axitinib is a potent inhibitor of human CYP1A2.
AB  - The tyrosine kinase inhibitors (TKIs) and multikinase inhibitors (MKIs) are
      oncology drugs of increasing importance that have improved the treatment of
      multiple tumors types. In some patients these agents produce adverse effects,
      including pharmacokinetic drug-drug interactions, due to cytochrome P450 (CYP)
      inhibition. Information on the propensity of the drugs to elicit such effects
      often only becomes evident as the drugs enter clinical use. The present study
      assessed 18 kinase inhibitors (1 and 50 MUM) for the inhibition of major drug
      metabolizing CYPs 1A2, 2C9, 2D6 and 3A4 in human liver microsomes. Most TKIs and
      MKIs inhibited CYP reactions at the higher concentration but axitinib also
      potently inhibited CYP1A2-dependent 7-ethoxyresorufin O-deethylation activity at
      the lower concentration. Kinetic analyses of CYP1A2 inhibition by axitinib were
      undertaken in microsomes and found a Ki of 0.11 +/- 0.01 MUM, which was 7.5-fold
      lower than the Km for 7-ethoxyresorufin oxidation (0.83 +/- 0.06 MUM); the
      inhibition mechanism was linear-mixed. From computational modeling two potential
      binding modes for axitinib were identified in the active site of CYP1A2: one in
      which the oxidizable axitinib thioether sulfur atom is within ~4.45 A of the
      CYP1A2 heme, and is likely to favor biotransformation of the drug, and a second
      in which the pyridine moiety is in proximity to the heme, which may contribute to
      inhibition. The applicability of these findings to potential pharmacokinetic
      interactions in patients during axitinib treatment should now be assessed.

PMID- 24462922
TI  - The enrichment of natural radionuclides in oil shale-fired power plants in
      Estonia--the impact of new circulating fluidized bed technology.
AB  - Burning oil shale to produce electricity has a dominant position in Estonia's
      energy sector. Around 90% of the overall electric energy production originates
      from the Narva Power Plants. The technology in use has been significantly
      renovated - two older types of pulverized fuel burning (PF) energy production
      units were replaced with new circulating fluidized bed (CFB) technology.
      Additional filter systems have been added to PF boilers to reduce emissions. Oil
      shale contains various amounts of natural radionuclides. These radionuclides
      concentrate and become enriched in different boiler ash fractions. More volatile
      isotopes will be partially emitted to the atmosphere via flue gases and fly ash.
      To our knowledge, there has been no previous study for CFB boiler systems on
      natural radionuclide enrichment and their atmospheric emissions. Ash samples were
      collected from Eesti Power Plant's CFB boiler. These samples were processed and
      analyzed with gamma spectrometry. Activity concentrations (Bq/kg) and enrichment
      factors were calculated for the (238)U ((238)U, (226)Ra, (210)Pb) and (232)Th
      ((232)Th, (228)Ra) family radionuclides and for (40)K in different CFB boiler ash
      fractions. Results from the CFB boiler ash sample analysis showed an increase in
      the activity concentrations and enrichment factors (up to 4.5) from the furnace
      toward the electrostatic precipitator block. The volatile radionuclide ((210)Pb
      and (40)K) activity concentrations in CFB boilers were evenly distributed in
      finer ash fractions. Activity balance calculations showed discrepancies between
      input (via oil shale) and output (via ash fractions) activities for some
      radionuclides ((238)U, (226)Ra, (210)Pb). This refers to a situation where the
      missing part of the activity (around 20% for these radionuclides) is emitted to
      the atmosphere. Also different behavior patterns were detected for the two Ra
      isotopes, (226)Ra and (228)Ra. A part of (226)Ra input activity, unlike (228)Ra,
      was undetectable in the solid ash fractions of the boiler. Most probably it is
      released to the surrounding environment. 

PMID- 24462923
TI  - Radiobiological long-term accumulation of environmental alpha radioactivity in
      extracted human teeth and animal bones in Malaysia.
AB  - In this study, the radiobiological analysis of natural alpha emitters in
      extracted human teeth and animal bones from Malaysia was estimated. The
      microdistributions of alpha particles in tooth and bone samples were measured
      using CR-39 alpha-particle track detectors. The lowest and highest alpha emission
      rates in teeth in the Kedah and Perak states were 0.0080 +/- 0.0005 mBq cm(-2)
      and 0.061 +/- 0.008 mBq cm(-2), whereas those of bones in the Perlis and Kedah
      states were 0.0140 +/- 0.0001 mBq cm(-2) and 0.7700 +/- 0.0282 mBq cm(-2),
      respectively. The average alpha emission rate in male teeth was 0.0209 +/- 0.0008
      mBq cm(-2), whereas that of female teeth was 0.0199 +/- 0.0010 mBq cm(-2). The
      alpha emission rate in teeth is higher in smokers (0.0228 +/- 0.0008 mBq cm(-2))
      than in non-smokers (0.0179 +/- 0.0008 mBq cm(-2)). Such difference was found
      statistically significant (p < 0.01).

PMID- 24462925
TI  - Cruel nature: Harmfulness as an important, overlooked dimension in judgments of
      moral standing.
AB  - Entities that possess moral standing can be wronged and deserve our moral
      consideration. Past perspectives on the folk psychology of moral standing have
      focused exclusively on the role of "patiency" (the capacity to experience pain or
      pleasure) and "agency" (usually defined and operationalized in terms of
      intelligence or cognitive ability). We contend that harmfulness (i.e., having a
      harmful vs. benevolent disposition) is an equally if not more important
      determinant of moral standing. We provide support for this hypothesis across four
      studies using non-human animals as targets. We show that the effect of
      harmfulness on attributions of moral standing is independent from patiency and
      intelligence (Studies 1-2), that this effect pertains specifically to an animal's
      harmful disposition rather than its capacity to act upon this disposition (Study
      3), and that it primarily reflects a parochial concern for human welfare in
      particular (Study 4). Our findings highlight an important, overlooked dimension
      in the psychology of moral standing that has implications for real-world
      decisions that affect non-human animals. Our findings also help clarify the
      conditions under which people perceive patiency and agency as related versus
      truly independent dimensions. 

PMID- 24462924
TI  - Determination of 40K, 232Th and 238U activity concentrations in ambient PM2.5
      aerosols and the associated inhalation effective dose to the public in Jeddah
      City, Saudi Arabia.
AB  - Natural radioactivity of soil samples has been studied in many countries of the
      Arabian Peninsula, including Saudi Arabia. Radiological indices based on soil
      radioactivity have been widely used in these studies. However, there are no
      available data about natural radioactivity of fine aerosol particles in such
      countries. The objective of this study is to determine the activity
      concentrations of (40)K, (232)Th and (238)U in airborne PM2.5 and the associated
      internal inhalation radiation dose to the public in Jeddah City, Saudi Arabia.
      Twenty-four air samples in four locations throughout Jeddah were collected and
      analyzed for PM2.5 and the associated K, Th and U. The activity concentrations of
      the isotopes (40)K, (232)Th and (238)U were calculated. High atmospheric PM2.5
      concentrations (mean: 50.81 +/- 34.02 MUg/m(3)) were found. The natural
      radioactivity associated with PM2.5 due to the isotopes (40)K, (232)Th and (238)U
      were 301.8 +/- 76.1, 11.8 +/- 4.2 and 10.8 +/- 3.4 Bq/kg, respectively, and the
      Raeq was calculated as 44.9 +/- 14.0 Bq/kg. The inhalation annual effective
      radiation dose to the public due to natural isotopes of the airborne PM2.5 was in
      the range 15.03-58.87 nSv/year, depending on the age group. Although these dose
      values were associated with the PM2.5 fraction only, they were higher than the
      world references values in air reported in the UNSCEAR, 2000 report.

PMID- 24462926
TI  - Revisiting the limits of language: the odor lexicon of Maniq.
AB  - It is widely believed that human languages cannot encode odors. While this is
      true for English, and other related languages, data from some non-Western
      languages challenge this view. Maniq, a language spoken by a small population of
      nomadic hunter-gatherers in southern Thailand, is such a language. It has a
      lexicon of over a dozen terms dedicated to smell. We examined the semantics of
      these smell terms in 3 experiments (exemplar listing, similarity judgment and off
      line rating). The exemplar listing task confirmed that Maniq smell terms have
      complex meanings encoding smell qualities. Analyses of the similarity data
      revealed that the odor lexicon is coherently structured by two dimensions. The
      underlying dimensions are pleasantness and dangerousness, as verified by the off
      line rating study. Ethnographic data illustrate that smell terms have detailed
      semantics tapping into broader cultural constructs. Contrary to the widespread
      view that languages cannot encode odors, the Maniq data show odor can be a
      coherent semantic domain, thus shedding new light on the limits of language. 

PMID- 24462927
TI  - Reductive dechlorination of 1,2,3,7,8-pentachlorodibenzo-p-dioxin and Aroclor
      1260, 1254 and 1242 by a mixed culture containing Dehalococcoides mccartyi strain
      195.
AB  - A mixed culture containing Dehalococcoides mccartyi strain 195 dechlorinated
      1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PeCDD) and selected
      polychlorinated biphenyl (PCB) congeners in Aroclors 1260, 1254 and 1242.
      1,2,3,7,8-PeCDD was dechlorinated to 1,3,7-trichlorodibenzo-p-dioxin (1,3,7
      TrCDD) and/or 1,3,8-TrCDD via 1,3,7,8-tetrachlorodibenzo-p-dioxin (1,3,7,8
      TeCDD), a pathway that excludes the production of the toxic congener 2,3,7,8
      TeCDD. Dechlorination rate and extent was greatly enhanced by the addition of
      1,2,3,4-tetrachlorobenzene (1,2,3,4-TeCB) as an alternate halogenated substrate
      and/or incubation temperature increase from 25  degrees C to 35  degrees C. The
      most extensive dechlorination of PCBs occurred for Aroclor 1260 with 13 major
      congeners making up 44.1 mol% of the original PCBs dechlorinated by 42% over 250
      days at 25  degrees C. When 1,2,3,4-TeCB was amended as co-substrate, the extent
      of dechlorination increased to 82%, over 250 days. The mixed culture primarily
      dechlorinated the doubly-flanked chlorines on 2,3,4-, 2,3,4,6-, and 2,3,4,5,6
      substituted chlorophenyl rings, whereas it primarily removed the doubly-flanked
      para chlorine from the 2,3,4,5-substituted chlorophenyl ring. Experiments using a
      20% dilution of culture with 31.8 MUg/mL 1,2,3,4-TeCDD or 2,3,4,4',5
      pentachlorobiphenyl (PCB 114) as sole halogenated substrate exhibited less than
      0.1 mol% dechlorination over 120 days. Further, dechlorination of PCBs and PCDDs
      by the fully grown culture in the absence of 1,2,3,4-TeCB eventually stopped or
      greatly slowed over the incubation period. Since Dehalococcoides spp. only gain
      energy for growth from organohalide respiration, absence of reductive
      dechlorination upon transfer and dilution or cessation of dechlorination after
      long incubation times suggest that it is unlikely that strain 195 can grow using
      the PCDDs or PCBs utilized in this study. 

PMID- 24462928
TI  - Cyanobacterium Microcystis aeruginosa response to pentachlorophenol and
      comparison with that of the microalga Chlorella vulgaris.
AB  - Pentachlorophenol (PCP) effects on a strain of the cyanobacterium Microcystis
      aeruginosa were investigated at laboratory scale. This is the first systematic
      ecotoxicity study of the effects of PCP on an aquatic cyanobacterium. The
      microalga Chlorella vulgaris was studied in the same conditions as the
      cyanobacterium, in order to compare the PCP toxicity and its removal by the
      species. The cells were exposed to environmental levels of PCP during 10 days, in
      Fraquil culture medium, at nominal concentrations from 0.01 to 1000 MUg L(-1), to
      the cyanobacterium, and 0.01 to 5000 MUg L(-1), to the microalga. Growth was
      assessed by area under growth curve (AUC, optical density vs time) and
      chlorophyll a content (chla). The toxicity profiles of the two species were very
      different. The calculated effective concentrations EC20 and EC50 were much lower
      to M. aeruginosa, and its growth inhibition expressed by chla was concentration
      dependent while by AUC was not concentration-dependent. The cells might continue
      to divide even with lower levels of chla. The number of C. vulgaris cells
      decreased with the PCP concentration without major impact on the chla. The effect
      of PCP on M. aeruginosa is hormetic: every concentration studied was toxic except
      1 MUg L(-1), which promoted its growth. The legal limit of PCP set by the
      European Union for surface waters (1 MUg L(-1)) should be reconsidered since a
      toxic cyanobacteria bloom might occur. The study of the removal of PCP from the
      culture medium by the two species is an additional novelty of this work. M.
      aeruginosa could remove part of the PCP from the medium, at concentrations where
      toxic effects were observed, while C. vulgaris stabilized it. 

PMID- 24462929
TI  - Toxicity assessment of chlorinated wastewater effluents by using transcriptome
      based bioassays and Fourier transform mass spectrometry (FT-MS) analysis.
AB  - Effects of chlorination on the toxicity of wastewater effluents treated by
      activated sludge (AS) and submerged membrane bioreactor (S-MBRB) systems to HepG2
      human hepatoblastoma cells were investigated. In addition to the cytotoxicity and
      genotoxicity assays, the DNA microarray-based transcriptome analysis was
      performed to evaluate the change in types of biological impacts on HepG2 cells of
      the effluents by chlorination. Effluent organic matter (EfOM) and disinfection by
      products (DBPs) were also characterized by using Fourier transform mass
      spectrometry (FT-MS). Although no significant induction of genotoxicity was
      observed by chlorination for both effluents, the chlorination elevated the
      cytotoxicity of AS effluent but reduced that of S-MBRB effluent. The FT-MS
      analyses revealed that more DBPs including nitrogenated DBPs (N-DBPs) were formed
      in the AS effluent than in the S-MBRB effluent by chlorination, supporting the
      increased cytotoxicity of AS effluent. The lower O/C ratio of S-MBRB EfOM
      suggests that a large number of organic molecules were detoxified by
      chlorination, which consequently decreased the cytotoxicity of S-MBRB effluent.
      Integration of all the results highlights that both cytotoxicity and biological
      impacts of chlorinated wastewater effluents were clearly dependent on the EfOM
      characteristics such as DBPs and O/C ratio, namely, on types of treatment
      systems. 

PMID- 24462930
TI  - Serotypes and antibiotic resistance of non-invasive Streptococcus pneumoniae
      circulating in pediatric hospitals in Moscow, Russia.
AB  - BACKGROUND: Pneumococcal infections remain a major medical problem associated
      with high morbidity and mortality. Moreover, the resistance of Streptococcus
      pneumoniae to conventional antibiotics is constantly growing. The implementation
      of pneumococcal conjugate vaccines (PCVs) in the last decade has dramatically
      reduced the incidence of the vaccine type-associated invasive pneumococcal
      diseases in many countries. However, information on the seroepidemiology of S.
      pneumoniae in Russia is limited. METHODS: We report the results of serotyping and
      antibiotic susceptibility testing performed on 863 non-invasive pneumococcal
      isolates collected prospectively in 2009-2013 from children (median age 3.5
      years) who sought medical care at five pediatric hospitals in Moscow. The
      isolates were recovered from the nasopharynx (71.2%), middle ear fluid (14.3%),
      and lower respiratory tract specimens (13.6%). RESULTS: In total, we identified
      45 different serotypes. The six leading serotypes (prevalence >5%) included 19F
      (21.7%), 6B (12.8%), 23F (10.1%), 14 (9.0%), 6A (8.4%), and 3 (7.5%). Serotype
      19A isolates had a prevalence of 2.3%. The proportion of PCV-13 serotypes was
      78%; the coverage by PCV-7 was 58.2% and was similar to that of PCV-10 (59.8%).
      The rate of multidrug-resistant pneumococci (i.e., resistant to >=3
      antimicrobials) was 22%. The majority of the multidrug-resistant isolates were
      serotype 6B, 14, 19A, and 19F. Penicillin non-susceptibility was displayed by 28%
      of the isolates. The resistance rate to erythromycin was 26%. Among the examined
      erythromycin-resistant strains, 54% had the erm(B) gene and 13% had the mef gene
      as a single resistance determinant, whereas both determinants were found in 31%
      of these strains. CONCLUSIONS: Our data predict a good coverage of the
      circulating S. pneumoniae by the PCVs and could be useful for evaluating the
      serotype distribution in support of the introduction of PCV in Russia. In
      addition, the antimicrobial resistance rate of S. pneumoniae in Russia is
      substantial, and the emergence of pneumococcal strains with a dual macrolide
      resistance mechanism is alarming.

PMID- 24462931
TI  - Nocebo and placebo modulation of hypobaric hypoxia headache involves the
      cyclooxygenase-prostaglandins pathway.
AB  - Nocebo and placebo effects have been found to modulate several neurochemical
      systems, such as cholecystokinin, endogenous opioids, and endocannabinoids. Here
      we show that also the cyclooxygenase-prostaglandins pathway can be modulated by
      both nocebos and placebos. In fact, we found that negative expectation, the
      crucial element of the nocebo effect, about headache pain led to the enhancement
      of the cyclooxygenase-prostaglandins pathway, which, in turn, induced pain
      worsening. As an experimental model, we studied hypobaric hypoxia headache at
      high altitude in 2 populations of subjects. Whereas the experimental nocebo group
      received negative information by a single individual who was informed about the
      risk of headache, the control group did not know about the possible occurrence of
      headache. We found a significant increase in headache and salivary prostaglandins
      and thromboxane in the nocebo group compared to the control group, suggesting
      that negative expectations enhance cyclooxygenase activity. In addition, placebo
      administration to headache sufferers at high altitude inhibited the nocebo
      related component of pain and prostaglandins synthesis, which indicates that the
      cyclooxygenase pathway can be modulated by both nocebos and placebos. Our results
      show for the first time how nocebos and placebos affect the synthesis of
      prostaglandins, which represent an important target of analgesic drugs, thus
      emphasizing once again the notion that placebos and drugs may use common
      biochemical pathways. 

PMID- 24462932
TI  - Coolness both underlies and protects against the painfulness of the thermal grill
      illusion.
AB  - We investigated the contributions of warm and cool signals in generating the
      thermal grill illusion (TGI), a phenomenon in which interlaced warm and cool bars
      generate an experience of burning, and under some conditions painful, heat. Each
      subject underwent 3 runs, 2 of which tested the effects of preadapting subjects
      to the grill's warm or cool bars (while the interlaced bars were thermally
      neutral) on the subsequent intensity of the illusion. In a control run, all bars
      were neutral during the adaptation phase. Thermal visual analogue scale ratings
      during the warm and cool adaptation periods revealed significant and equivalent
      adaptation to the 2 temperatures. Adaptation to the grill's cool bars
      significantly reduced pain and perceived thermal intensity of the TGI, compared
      to the control condition, while adaptation to the grill's warm bars had little
      effect. These results suggest that the cool stimulus triggers the pain signals
      that produce the illusion. The inability of warm adaptation to attenuate the TGI
      is at odds with theories suggesting that the illusion depends upon a simple
      addition of warm and cool signals. While the grill's cool bars are necessary for
      the TGI's painfulness, we also observed that the more often a participant
      reported feeling coolness or coldness, the less pain he or she experienced from
      the TGI. These results are consistent with research showing that cool
      temperatures generate activity in both thermoreceptive-specific, pain-inhibitory
      neurons and nociceptive dorsal horn neurons. 

PMID- 24462933
TI  - Not so harmless anymore: how context impacts the perception and electrocortical
      processing of neutral faces.
AB  - Our first impression of others is highly influenced by their facial appearance.
      However, the perception and evaluation of faces is not only guided by internal
      features such as facial expressions, but also highly dependent on contextual
      information such as secondhand information (verbal descriptions) about the target
      person. To investigate the time course of contextual influences on cortical face
      processing, event-related brain potentials were investigated in response to
      neutral faces, which were preceded by brief verbal descriptions containing cues
      of affective valence (negative, neutral, positive) and self-reference (self
      related vs. other-related). ERP analysis demonstrated that early and late stages
      of face processing are enhanced by negative and positive as well as self-relevant
      descriptions, although faces per se did not differ perceptually. Affective
      ratings of the faces confirmed these findings. Altogether, these results
      demonstrate for the first time both on an electrocortical and behavioral level
      how contextual information modifies early visual perception in a top-down manner.

PMID- 24462934
TI  - Morphosyntax can modulate the N400 component: event related potentials to gender
      marked post-nominal adjectives.
AB  - Event-related potential studies of grammatical gender agreement often report a
      left anterior negativity (LAN) when agreement violations occur. Some studies have
      shown that during sentence comprehension gender violations can also interact with
      semantic processing to modulate a negativity associated with processing meaning -
      the N400. Given that the LAN and N400 overlap in time, they are identified by
      their scalp distributions and purported functional roles. Critically, grammatical
      gender violations also elicit a right posterior positivity that can overlap
      temporally and potentially affect the scalp distribution of the LAN/N400. We
      measured the effect of grammatical gender violations in the LAN/N400 window and
      late positive component (LPC) during comprehension of Spanish sentences. A post
      nominal adjective could either make sense or not, and either agree or disagree in
      gender with the preceding noun. We observed a negativity to gender agreement
      violations in the LAN/N400 window (300-500ms post stimulus onset) that was
      smaller than the semantic-congruity N400, but overlapped with it in time and
      distribution. The early portion of the LPC to gender violations was modulated by
      sentence constraint, occurring as early as 450ms in highly constraining
      sentences. A subadditive interaction occurred at the later portion of the LPC
      with equivalent effects for single and double violations (gender and semantics),
      reflecting a general stage of reprocessing. Overall, our data support models of
      language comprehension whereby both semantic and morphosyntactic information can
      affect processing at similar time points. 

PMID- 24462935
TI  - Rapamycin induces of protective autophagy in vascular endothelial cells exposed
      to oxygen-glucose deprivation.
AB  - The protective potential of rapamycin has been reported in a few experimental
      models of brain ischemia, both in vivo and in vitro. Although the precise
      cellular processes underlying the neuroprotective effects of rapamycin in
      experimental models of stroke remain unknown, the current experimental data
      suggest that the mechanism of action of the drug may result from the mTOR
      mediated autophagy induction. However, it is unclear whether the activation of
      autophagy acts as a pro-death or pro-survival factor in vascular endothelial
      cells in ischemic brain damage. It seems to be very important, since stroke
      affects not only neurons and astrocytes but also microvessels. In the present
      study, we used human umbilical vein endothelial cells (HUVEC) subjected to
      ischemia-simulating conditions (combined oxygen and glucose deprivation, OGD) for
      6h to determine potential effect of rapamycin-induced autophagy on HUVEC damage.
      The drug at concentrations of 100 and 1000nM increased the expression of Beclin 1
      and LC3-II together with a significant increase in the p62 degradation in
      ischemic HUVEC. Treatment with rapamycin in OGD significantly increased the cell
      viability, indicating that the drug exerts cytoprotective effect. The inhibition
      of Beclin 1 by siRNAs significantly attenuated the expression of autophagy
      related proteins and reduced HUVEC viability following OGD and rapamycin
      treatment. Our findings demonstrated that toxicity of simulated ischemia
      conditions were enhanced in HUVEC when autophagy was blocked, and that rapamycin
      effectively prevented OGD-evoked damage by induction of protective autophagy via
      inhibition of the mTOR pathway. 

PMID- 24462937
TI  - Does oxytocin modulate variation in maternal caregiving in healthy new mothers?
AB  - BACKGROUND: Maternal sensitivity to infant cues and developmental needs may be
      pivotal for social and cognitive development. Animal and recent human studies
      emphasise a major role for Oxytocin (OT) in mediating sensitive caregiving but no
      study has examined the relationship between OT and extreme variation in human
      maternal sensitivity. METHODS: From 105 expectant mothers, 80 underwent blind
      rating of maternal sensitivity at 4-6 months postpartum through free-play
      interaction with their infants. At 7-9 months postpartum, 30 mothers at extremes
      of maternal sensitivity: 15 'sensitive mothers' (high sensitivity mothers - HSMs,
      mean=4.47; SD=0.74) and 15 'less sensitive mothers' (low sensitivity mothers -
      LSMs, mean=2.13; SD=0.52) underwent plasma OT measurements before and after 10
      min infant play. RESULTS: Baseline and post-interaction plasma OT was higher in
      LSMs than HSMs [F(1, 26)=8.42; p=0.01]. HSMs showed a trend towards significant
      reduction in plasma OT [t(14)=2.01; p=0.06] following play-interaction; no change
      was shown by LSMs [t(13)=-0.14; p=0.89]. Conclusion Higher baseline OT levels in
      healthy LSMs may imply greater stress responses to the demands of caring for an
      infant, or past deficiencies in own parenting relationship and act as a biomarker
      for poor parental sensitivity. OT may be acting to reduce stress and anxiety in
      LSMs consistent with studies of plasma OT and stress in women. By contrast, in
      HSMs, play interaction with their infants maybe relaxing as indicated by
      significant reduction in plasma OT from baseline. Ascertainment of mothers in
      well-defined sensitivity groups might facilitate examination of distinct coping
      strategies in parents and better understanding of variation in parental
      caregiving behaviour and its potential for modulation by OT. This article is part
      of a Special Issue entitled Oxytocin and Social Behav.

PMID- 24462938
TI  - WITHDRAWN: Enkephalin- and dynorphin-release produced by electrical stimulation
      of different frequencies in rat brain slices.
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- 24462939
TI  - Long-term improvements in sensory inhibition with gestational choline
      supplementation linked to alpha7 nicotinic receptors through studies in Chrna7
      null mutation mice.
AB  - Perinatal choline supplementation has produced several benefits in rodent models,
      from improved learning and memory to protection from the behavioral effects of
      fetal alcohol exposure. We have shown that supplemented choline through gestation
      and lactation produces long-term improvement in deficient sensory inhibition in
      DBA/2 mice which models a similar deficit in schizophrenia patients. The present
      study extends that research by feeding normal or supplemented choline diets to
      DBA/2 mice carrying the null mutation for the alpha7 nicotinic receptor gene
      (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were
      placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at
      mating and remained on the specific diet until offspring weaning. Thereafter,
      offspring were fed standard rodent chow. Adult offspring were assessed for
      sensory inhibition. Brains were obtained to ascertain hippocampal alpha7
      nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant
      for Chrna7 failed to show improvement in sensory inhibition. Only wildtype
      choline-supplemented mice showed improvement with the effect solely through a
      decrease in test amplitude. This supports the hypothesis that gestational-choline
      supplementation is acting through the alpha7 nicotinic receptor to improve
      sensory inhibition. Although there was a significant gene-dose-related change in
      hippocampal alpha7 receptor numbers, binding studies did not reveal any choline
      dose-related change in binding in any hippocampal region, the interaction being
      driven by a significant genotype main effect (wildtype>heterozygote>null mutant).
      These data parallel a human study wherein the offspring of pregnant women
      receiving choline supplementation during gestation, showed better sensory
      inhibition than offspring of women on placebo.

PMID- 24462940
TI  - Spatial and temporal distributions of phlebotomine sand flies (Diptera:
      Psychodidae), vectors of leishmaniasis, in Iran.
AB  - Leishmaniasis is a major vector-borne disease and health problem in Iran. Studies
      on sand flies, as the vectors of the disease, began in the Northern and Western
      parts of the country in 1930 and have been continued up to now. Concerning many
      published information in the field of sand flies, providing a digital database
      for the country will help the public health authorities to make more correct and
      prompt decisions for planning leishmaniasis control programs as well as modeling
      and forecasting of transmission potential across the country. All published data
      on phlebotomine sand flies of Iran were collected. A database was then designed
      in Excel format, including all available information regarding sand flies. The
      valid data were transferred to ArcGIS9.3 to prepare the first spatial database of
      sand flies of Iran. The IrSandflybase includes 131 papers, 2 abstracts and 71
      PhD/MSc theses, reporting studies conducted during 1930-2012. This database
      contains different available data covering all aspects of ecology and biology of
      50 sand fly species in two genera of Phlebotomus and Sergentomyia in the country.
      The temporal activity of sand flies is reported 9 months in warm regions of the
      southern part, while it may reduce to 7-8 months in central plateau or 4-5 months
      in cold areas of the northwest. Occasional studies reported rare species from the
      borderlines of Iran. It seems that changing the climate due to global warming may
      affect the spatial distribution of different species and expand it into the
      country, the issue that can be followed by an updated database. 

PMID- 24462941
TI  - Will the introduction of Leishmania tropica MON-58, in the island of Crete, lead
      to the settlement and spread of this rare zymodeme?
AB  - The rare zymodeme, Leishmania tropica MON-58, was isolated from a young Afghan
      refugee with a facial cutaneous lesion who had come to live in Crete early 2008.
      The same zymodeme variant was isolated from a local dog that had never travelled
      outside the island, with symptoms of visceral leishmaniasis, which stayed in the
      area where the patient worked during the summer months. This is the first record
      of L. tropica in a host, other than human, in Greece and another example of
      introduction of a vector borne pathogen in a focus where local vector/s can
      sustain it, with the risk of initiation of new transmission cycle/s. 

PMID- 24462942
TI  - Dosimetric characteristics of a radiochromic polyvinyl butyral film containing
      2,4-hexadiyn-1,6-bis(n-butyl urethane).
AB  - A radiation-sensitive compound 2,4-hexadiyn-1,6-bis(n-butyl urethane) (HDDBU) was
      synthesized, characterized by FTIR spectroscopy, and introduced into a thin
      polyvinyl butyral film to form a radiation dosimeter for industrial irradiation
      facilities. The monomer polymerizes under gamma radiation, inducing change in the
      film spectrum in the range of 200-400 nm. According to XRD spectroscopy, the film
      contains monomeric HDDBU in a non-crystalline state. The dose response function,
      radiation sensitivity, and dependences of the response on environmental factors
      were studied. Uncertainty of dose measurements with the proposed dosimetry system
      was analyzed in detail.

PMID- 24462936
TI  - Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental
      disorders.
AB  - Oxytocin (OT) and arginine vasopressin (AVP) are two small, related neuropeptide
      hormones found in many mammalian species, including humans. Dysregulation of
      these neuropeptides have been associated with changes in behavior, especially
      social interactions. We review how the OT and AVP systems have been investigated
      in Autism Spectrum Disorder (ASD), Prader-Willi Syndrome (PWS), Williams Syndrome
      (WS) and Fragile X syndrome (FXS). All of these neurodevelopmental disorders
      (NDD) are marked by social deficits. While PWS, WS and FXS have identified
      genetic mutations, ASD stems from multiple genes with complex interactions.
      Animal models of NDD are invaluable for studying the role and relatedness of OT
      and AVP in the developing brain. We present data from a FXS mouse model affecting
      the fragile X mental retardation 1 (Fmr1) gene, resulting in decreased OT and AVP
      staining cells in some brain regions. Reviewing the research about OT and AVP in
      these NDD suggests that altered OT pathways may be downstream from different
      etiological factors and perturbations in development. This has implications for
      ongoing studies of the therapeutic application of OT in NDD. This article is part
      of a Special Issue entitled Oxytocin and Social Behav. 

PMID- 24462943
TI  - Determination of 90Sr and 210Pb in sludge samples using a LOV-MSFIA system and
      liquid scintillation counting.
AB  - There has been increasing interest recently in the capacity of water treatment
      plants to concentrate and eliminate radionuclides from raw water. As the normal
      operation in these plants generates high quantities of sludge, which can be
      considered a naturally occurring radioactive material, it is important to gather
      information about its radiological content. Therefore, in order to determine the
      activity values of two radioactive beta emitters with minimal sample
      manipulation, an automated lab-on-valve and multisyringe flow injection system
      has been developed to achieve the sequential preconcentration and separation of
      (90)Sr and (210)Pb using an extraction chromatographic resin (Sr-spec).
      Activities of both isotopes were measured by liquid scintillation counting (LSC).
      The developed method was validated by analyzing three samples from three
      different intercomparison exercises and good Z-score values (between 0.1 and 1)
      and trueness values (between 10% and 17%) were obtained. The method was then also
      satisfactorily applied to sludge samples taken from a Spanish drinking water
      treatment plant which treats water from the Ebro River. The proposed method
      offers advantages over existing methods as it allows the sequential separation of
      both isotopes, simply by changing the elution conditions and using a semi
      automated approach. Therefore, the method is less time consuming and
      environmentally friendly. 

PMID- 24462944
TI  - Microfocus X-ray imaging of the internal geometry of brachytherapy seeds.
AB  - Precise and reliable geometrical data on the internal structure of seeds are
      indispensable for dosimetric calculation in brachytherapy. We used a novel
      microfocus X-ray imaging technique for observing the internal structure of
      brachytherapy seeds. Two popular (125)I seed models were evaluated. Obtained high
      precision images enabled us to observe the internal structure of seeds
      qualitatively. Geometrical size parameters were evaluated quantitatively with
      uncertainty of 0.01-0.04 mm (k=2).

PMID- 24462945
TI  - The anti-proliferative effect of metformin in triple-negative MDA-MB-231 breast
      cancer cells is highly dependent on glucose concentration: implications for
      cancer therapy and prevention.
AB  - BACKGROUND: Metformin has been shown to have a strong anti-proliferative effect
      in many breast cancer cell lines, mainly due to the activation of the energy
      sensing kinase, AMP-activated protein kinase (AMPK). MDA-MB-231 cells are
      aggressive and invasive breast cancer cells that are known to be resistant to
      several anti-cancer agents as well as to the anti-proliferative effect of
      metformin. As metformin is a glucose lowering drug, we hypothesized that
      normoglycemia will sensitize MDA-MB-231 cells to the anti-proliferative effect of
      metformin. METHODS: MDA-MB-231 cells were treated with increasing metformin
      concentrations in hyperglycemic or normoglycemic conditions. The growth
      inhibitory effect of metformin was assessed by MTT assay. The expression of
      several proteins involved in cell proliferation was measured by Western blotting.
      RESULTS: In agreement with previous studies, treatment with metformin did not
      inhibit the growth of MDA-MB-231 cells cultured in hyperglycemic conditions.
      However, metformin significantly inhibited MDA-MB-231 growth when the cells were
      cultured in normoglycemic conditions. In addition, we show that metformin
      treatment of MDA-MB-231 cells cultured in normoglycemic conditions and not in
      hyperglycemic conditions caused a striking activation of AMPK, and an AMPK
      dependent inhibition of multiple molecular signaling pathways known to control
      protein synthesis and cell proliferation. CONCLUSION: Our data show that
      normoglycemia sensitizes the triple negative MDA-MB-231 breast cancer cells to
      the anti-proliferative effect of metformin through an AMPK-dependent mechanism.
      GENERAL SIGNIFICANCE: These findings suggest that tight normoglycemic control may
      enhance the anti-proliferative effect of metformin in diabetic cancer patients.

PMID- 24462946
TI  - Glycyrrhizin inhibits lipopolysaccharide-induced inflammatory response by
      reducing TLR4 recruitment into lipid rafts in RAW264.7 cells.
AB  - BACKGROUND: The aim of this study was to investigate the effect of glycyrrhizin
      on LPS-induced endotoxemia in mice and clarify the possible mechanism. METHODS:
      An LPS-induced endotoxemia mouse model was used to confirm the anti-inflammatory
      activity of glycyrrhizin in vivo. In vitro, RAW264.7 cells were stimulated with
      LPS in the presence or absence of glycyrrhizin. The expression of cytokines was
      determined by ELISA. Toll-like receptor 4 (TLR4) was determined by Western blot
      analysis. Nuclear factor-kB (NF-kappaB) and Interferon regulatory factor 3 (IRF3)
      activation were detected by Western blotting and luciferase assay. Lipid raft
      staining was detected by immunocytochemistry. RESULTS: In vivo, the results
      showed that glycyrrhizin can improve survival during lethal endotoxemia. In
      vitro, glycyrrhizin dose-dependently inhibited the expression of TNF-alpha, IL-6,
      IL-1beta and RANTES in LPS-stimulated RAW264.7 cells. Western blot analysis
      showed that glycyrrhizin suppressed LPS-induced NF-kappaB and IRF3 activation.
      However, glycyrrhizin did not inhibit NF-kappaB and IRF3 activation induced by
      MyD88-dependent (MyD88, IKKbeta) or TRIF-dependent (TRIF, TBK1) downstream
      signaling components. Moreover, glycyrrhizin did not affect the expression of
      TLR4 and CD14 induced by LPS. Significantly, we found that glycyrrhizin decreased
      the levels of cholesterol of lipid rafts and inhibited translocation of TLR4 to
      lipid rafts. Moreover, glycyrrhizin activated ABCA1, which could induce
      cholesterol efflux from lipid rafts. CONCLUSION: Glycyrrhizin exerts an anti
      inflammatory property by disrupting lipid rafts and inhibiting translocation of
      TLR4 to lipid rafts, thereby attenuating LPS-mediated inflammatory response.
      GENERAL SIGNIFICANCE: Learning the anti-inflammatory mechanism of glycyrrhizin is
      crucial for the anti-inflammatory drug development.

PMID- 24462947
TI  - Direct cytocidal effect of galectin-9 localized on collagen matrices on human
      immune cell lines.
AB  - BACKGROUND: There is a continuous demand for new immunosuppressive agents for
      organ transplantation. Galectin-9, a member of the galactoside-binding animal
      lectin family, has been shown to suppress pathogenic T-cell responses in
      autoimmune disease models and experimental allograft transplantation. In this
      study, an attempt has been made to develop new collagen matrices, which can cause
      local, contact-dependent immune suppression, using galectin-9 and collagen
      binding galectin-9 fusion proteins as active ingredients. METHODS: Galectin-9 and
      galectin-9 fusion proteins having collagen-binding domains (CBDs) derived from
      bacterial collagenases and a collagen-binding peptide (CBP) were tested for their
      ability to bind to collagen matrices, and to induce Jurkat cell death in solution
      and in the collagen-bound state. RESULTS: Galectin-9-CBD fusion proteins
      exhibited collagen-binding activity comparable to or lower than that of the
      respective CBDs, while their cytocidal activity toward Jurkat cells in solution
      was 80~10% that of galectin-9. Galectin-9 itself exhibited oligosaccharide
      dependent collagen-binding activity. The growth of Jurkat cells cultured on
      collagen membranes treated with galectin-9 was inhibited by~90%. The effect was
      dependent on direct cell-to-membrane contact. Galectin-9-CBD/CBP fusion proteins
      bound to collagen membranes via CBD/CBP moieties showed a low or negligible
      effect on Jurkat cell growth. CONCLUSIONS: Among the proteins tested, galectin-9
      exhibited the highest cytocidal effect on Jurkat cells in the collagen-bound
      state. The effect was not due to galectin-9 released into the culture medium but
      was dependent on direct cell-to-membrane contact. GENERAL SIGNIFICANCE: The study
      demonstrates the possible use of galectin-9-modified collagen matrices for local,
      contact-dependent immune suppression in transplantation.

PMID- 24462948
TI  - Region-specific contribution of the ventral tegmental area to heroin-induced
      conditioned immunomodulation.
AB  - Dopamine receptor stimulation is critical for heroin-conditioned
      immunomodulation; however, it is unclear whether the ventral tegmental area (VTA)
      contributes to this phenomenon. Hence, rats received repeated pairings of heroin
      with placement into a distinct environmental context. At test, they were re
      exposed to the previously heroin-paired environment followed by systemic
      lipopolysaccharide treatment to induce an immune response. Bilateral GABA agonist
      induced neural inactivation of the anterior, but not the posterior VTA, prior to
      context re-exposure inhibited the ability of the heroin-paired environment to
      suppress peripheral nitric oxide and tumor necrosis factor-alpha expression,
      suggesting a role for the anterior VTA in heroin-conditioned immunomodulation. 

PMID- 24462949
TI  - Terrestrial stress analogs for spaceflight associated immune system
      dysregulation.
AB  - Recent data indicates that dysregulation of the immune system occurs and persists
      during spaceflight. Impairment of immunity, especially in conjunction with
      elevated radiation exposure and limited clinical care, may increase certain
      health risks during exploration-class deep space missions (i.e. to an asteroid or
      Mars). Research must thoroughly characterize immune dysregulation in astronauts
      to enable development of a monitoring strategy and validate any necessary
      countermeasures. Although the International Space Station affords an excellent
      platform for on-orbit research, access may be constrained by technical,
      logistical vehicle or funding limitations. Therefore, terrestrial spaceflight
      analogs will continue to serve as lower cost, easier access platforms to enable
      basic human physiology studies. Analog work can triage potential in-flight
      experiments and thus result in more focused on-orbit studies, enhancing overall
      research efficiency. Terrestrial space analogs generally replicate some of the
      physiological or psychological stress responses associated with spaceflight.
      These include the use of human test subjects in a laboratory setting (i.e.
      exercise, bed rest, confinement, circadian misalignment) and human remote
      deployment analogs (Antarctica winterover, undersea, etc.) that incorporate
      confinement, isolation, extreme environment, physiological mission stress and
      disrupted circadian rhythms. While bed rest has been used to examine the effects
      of physical deconditioning, radiation and microgravity may only be simulated in
      animal or microgravity cell culture (clinorotation) analogs. This article will
      characterize the array of terrestrial analogs for spaceflight immune
      dysregulation, the current evidence base for each, and interpret the analog
      catalog in the context of acute and chronic stress. 

PMID- 24462950
TI  - Why we may not find intentions in the brain.
AB  - Intentions are commonly conceived of as discrete mental states that are the
      direct cause of actions. In the last several decades, neuroscientists have taken
      up the project of finding the neural implementation of intentions, and a number
      of areas have been posited as implementing these states. We argue, however, that
      the processes underlying action initiation and control are considerably more
      dynamic and context sensitive than the concept of intention can allow for.
      Therefore, adopting the notion of 'intention' in neuroscientific explanations can
      easily lead to misinterpretation of the data, and can negatively influence
      investigation into the neural correlates of intentional action. We suggest
      reinterpreting the mechanisms underlying intentional action, and we will discuss
      the elements that such a reinterpretation needs to account for.

PMID- 24462951
TI  - Intensive tool-practice and skillfulness facilitate the extension of body
      representations in humans.
AB  - The brain's representation of the body can be extended to include objects that
      are not originally part of the body. Various studies have found both extremely
      rapid extensions that occur as soon as an object is held, as well as extremely
      slow extensions that require weeks of training. Due to species and methodological
      differences, it is unclear whether the studies were probing different
      representations, or revealing multiple aspects of the same representation. Here,
      we present evidence that objects (cotton balls) held by a tool (chopsticks) are
      rapidly integrated into the body representation, as indexed by fading of the
      cotton balls (or 'second-order extensions') from a positive afterimage.
      Skillfulness with chopsticks was predictive of more rapid integration of the
      second-order cotton balls held by this tool. We also found that extensive
      training over a period of weeks augmented the level of integration. Together, our
      findings demonstrate integration of second-order objects held by tools, and
      reveal that the body representation probed by positive afterimages is subject to
      both rapid and slow processes of adaptive change.

PMID- 24462952
TI  - Fine-coarse semantic processing in schizophrenia: a reversed pattern of
      hemispheric dominance.
AB  - Left lateralization for language processing is a feature of neurotypical brains.
      In individuals with schizophrenia, lack of left lateralization is associated with
      the language impairments manifested in this population. Beeman's fine-coarse
      semantic coding model asserts left hemisphere specialization in fine (i.e.,
      conventionalized) semantic coding and right hemisphere specialization in coarse
      (i.e., non-conventionalized) semantic coding. Applying this model to
      schizophrenia would suggest that language impairments in this population are a
      result of greater reliance on coarse semantic coding. We investigated this
      hypothesis and examined whether a reversed pattern of hemispheric involvement in
      fine-coarse semantic coding along the time course of activation could be detected
      in individuals with schizophrenia. Seventeen individuals with schizophrenia and
      30 neurotypical participants were presented with two word expressions of four
      types: literal, conventional metaphoric, unrelated (exemplars of fine semantic
      coding) and novel metaphoric (an exemplar of coarse semantic coding). Expressions
      were separated by either a short (250 ms) or long (750 ms) delay. Findings
      indicate that whereas during novel metaphor processing, controls displayed a left
      hemisphere advantage at 250 ms delay and right hemisphere advantage at 750 ms,
      individuals with schizophrenia displayed the opposite. For conventional
      metaphoric and unrelated expressions, controls showed left hemisphere advantage
      across times, while individuals with schizophrenia showed a right hemisphere
      advantage. Furthermore, whereas individuals with schizophrenia were less accurate
      than control at judging literal, conventional metaphoric and unrelated
      expressions they were more accurate when judging novel metaphors. Results suggest
      that individuals with schizophrenia display a reversed pattern of lateralization
      for semantic coding which causes them to rely more heavily on coarse semantic
      coding. Thus, for individuals with schizophrenia, speech situation are always non
      conventional, compelling them to constantly seek for meanings and prejudicing
      them toward novel or atypical speech acts. This, in turn, may disadvantage them
      in conventionalized communication and result in language impairment.

PMID- 24462953
TI  - Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to
      paraquat: mitochondrial dysfunction and oxidative stress.
AB  - Recent studies suggest that traumatic brain injury (TBI) and pesticide exposure
      increase the risk of Parkinson's disease (PD), but the molecular mechanisms
      involved remain unclear. Using an in vitro model of TBI, we evaluated the role of
      mitochondrial membrane potential (DeltaPsim) and mitochondrial reactive oxygen
      species (ROS) induced by stretch on dopaminergic cell death upon paraquat
      exposure. Human dopaminergic neuroblastoma SH-SY5Y cells grown on silicone
      membrane were stretched at mild (25%) and moderate (50%) strain prior to paraquat
      exposure. We observed that moderate stretch (50% strain) increased the
      vulnerability of cells to paraquat demonstrated by the loss of plasma membrane
      integrity (propidium iodide-uptake) and decreased mitochondrial activity (MTT
      assay). Mitochondrial depolarization occurred immediately after stretch, while
      mitochondrial ROS increased rapidly and remained elevated for up to 4h after the
      stretch injury. Intracellular glutathione (GSH) stores were also transiently
      decreased immediately after moderate stretch. Cells treated with paraquat, or
      moderate stretch exhibited negligible mitochondrial depolarization at 48h post
      treatment, whereas in cells stretched prior to paraquat exposure, a significant
      mitochondrial depolarization occurred compared to samples exposed to either
      paraquat or stretch. Moderate stretch also increased mitochondrial ROS formation,
      as well as exacerbated intracellular GSH loss induced by paraquat. Overexpression
      of manganese superoxide dismutase (MnSOD) markedly diminished the deleterious
      effects of stretch in paraquat neurotoxicity. Our findings demonstrate that
      oxidative stress induced by mitochondrial dysfunction plays a critical role in
      the synergistic toxic effects of stretch (TBI) and pesticide exposure. Mitigation
      of oxidative stress via mitochondria-targeted antioxidants appears an attractive
      route for treatment of neurodegeneration mediated by TBI. 

PMID- 24462954
TI  - Efficacy of 2years of entecavir plus adefovir therapy in patients with chronic
      hepatitis B who had failed on prior nucleos(t)ide analog treatment.
AB  - Entecavir (ETV) plus adefovir (ADV) combination therapy may be a promising option
      for chronic hepatitis B (CHB) patients who have failed on prior nucleos(t)ide
      analog (NA) treatment. However, the long-term efficacy and safety of this
      combination are not well-defined. In a single-center, retrospective study, 104
      patients (mean age 31.7 years; 88.5% male) with HBV DNA >10(3)IU/mL who had
      received one or multiple prior NAs for ? 6 months (median 44.5 months) were
      treated for ? 24 months with ETV (0.5mg/day) plus ADV (10mg/day). Among patients
      with available samples, 44/90 (48.9%) had drug-resistant mutations. At 2 years,
      HBV DNA levels were undetectable (<12 IU/mL) in 52/104 (50.0%) patients. The mean
      HBV DNA level was 2.0 +/- 1.2 log 10 IU/mL, and it was decreased by 3.2 +/- 2.0
      log 10 IU/mL from the pre-combination treatment (V0) value. The 2-year HBeAg loss
      rate was 14.4% (13/90), HBeAg seroconversion rate was 10.0% (9/90), and ALT
      normalization rate was 75%. In multivariate analyses, the prior NA treatment
      duration, the V0 HBV DNA level, and the HBV DNA reduction at 1 year after ETV+ADV
      therapy were associated with the virological response after 2 years. No patients
      developed renal impairment, clinical decompensation or new HCC, and no relapses
      of HCC or deaths occurred. Thus, 2-year rescue therapy with ETV+ADV was effective
      and well-tolerated in CHB patients who had previously failed on multiple NA
      treatments. The HBV DNA level just before ETV+ADV combination therapy and the
      decrease of HBV DNA at 1 year could predict the efficacy of 2 years of ETV+ADV
      treatment.

PMID- 24462955
TI  - Influence of low-density lipoprotein cholesterol on virological response to
      telaprevir-based triple therapy for chronic HCV genotype 1b infection.
AB  - Elevated serum low-density lipoprotein cholesterol (LDL-C) level has been
      associated with sustained virological response (SVR) by chronic hepatitis C
      patients treated with pegylated-interferon (PEG-IFN) alpha and ribavirin (RBV).
      The aim of this study was to investigate the relation between the baseline LDL-C
      level and the treatment outcome from telaprevir (TVR)-based triple therapy. This
      prospective, multicenter study consisted of 241 treatment-experienced patients
      infected with HCV genotype 1b. All received 12 weeks of TVR in combination with
      24 weeks of PEG-IFNalpha2b and RBV. The SVR rate was 81.3% (196 of 241) by
      intention-to-treat analysis. Higher LDL-C level was strongly associated with SVR
      (P=1.3*10-8). The area under the receiver operating characteristic curve for
      predicting SVR was 0.78 and the cutoff value for the LDL-C level at baseline was
      95 mg/dL. In multivariable logistic regression analysis of predictors of SVR, LDL
      C >=95 mg/dL (odds ratio [OR] 3.60, P=0.0238), alpha-fetoprotein <=5.0 ng/mL (OR
      5.06, P=0.0060), prior relapse to PEG-IFNalpha and RBV (OR 5.71, P=0.0008), and
      rapid virological response (HCV RNA undetectable at week 4) (OR 5.52, P=0.0010)
      were extracted as independent predictors of SVR. For prior partial and null
      responders, the SVR rates of the groups with LDL-C >=95 mg/dL were significantly
      higher than those of the <95 mg/dL groups with IL28B TG/GG and pretreatment
      platelet count <150*109/L (both P<0.05). The baseline LDL-C level exerted a
      potent influence on the SVR of treatment-experienced patients treated with TVR
      based triple therapy, especially for prior partial and null responders to PEG
      IFNalpha and RBV.

PMID- 24462956
TI  - How drug-like are 'ugly' drugs: do drug-likeness metrics predict ADME behaviour
      in humans?
AB  - Using a published drug-likeness score based on the calculated physicochemical
      properties of marketed oral drugs (quantitative estimate of drug-likeness, QED)
      and published human data, high-scoring and low-scoring drugs were compared to
      determine how well the score correlated with their actual pharmaceutical and
      pharmacokinetic (PK) profiles in humans. Drugs with high QED scores exhibit
      higher absorption and bioavailability, are administered at lower doses and have
      fewer drug-drug interaction warnings, P-glycoprotein interactions and absorption
      issues due to a food effect. By contrast, the high-scoring drugs exhibit similar
      behaviour to low-scoring drugs with respect to free fraction in plasma, extent of
      gut-wall metabolism, first-pass hepatic extraction, elimination half-life,
      clearance, volume of distribution and frequency of dosing. 

PMID- 24462957
TI  - Thorium induced cytoproliferative effect in human liver cell HepG2: role of
      insulin-like growth factor 1 receptor and downstream signaling.
AB  - Thorium-232 ((232)Th), a naturally-occurring actinide has gained significant
      attention due to its immense potential as a nuclear fuel for advanced reactors.
      Understanding the biological effects of (232)Th would significantly impact its
      efficient utilization with adequate health protection. Humans administered with
      (232)Th (thorotrast patients) or experimental animal models showed that liver is
      one of the major sites of (232)Th accumulation. Present study reports cellular
      effects of (232)Th-nitrate in a human-derived liver cell (HepG2). Results showed
      that the low concentration of (232)Th (0.1-10 MUM) induced proliferation of HepG2
      cells which was inhibited by the pre-treatment of cells with neutralizing
      antibody against insulin-like growth factor 1 receptor (IGF-1R). Consistently,
      (232)Th treatment was found to increase the phosphorylated level of IGF-1R
      associated molecule, IRS1 which serves to activate PI3K and MAPK signaling
      pathways. Pre-treatment with specific inhibitors of PI3K (LY294002) or JNK-MAPK
      (SP600125) significantly abrogated the cytoproliferative effect of (232)Th.
      Immunofluorescence analysis showed increased levels of phospho-Akt and phospho
      JNK, downstream kinases of IGF-1R, in (232)Th-treated HepG2 cells suggesting the
      role of IGF-1R-mediated signaling in (232)Th-stimulated cell proliferation. The
      cell cycle analysis showed that (232)Th increased S and G2-M cell fractions
      concomitant to the increase of cyclin-E level. Thus, the present investigation
      highlights the role of IGF-1R-mediated signaling in the cytoproliferative effect
      of (232)Th in human liver cells at low concentration.

PMID- 24462958
TI  - Phytic acid enhances the oral absorption of isorhamnetin, quercetin, and
      kaempferol in total flavones of Hippophae rhamnoides L.
AB  - AIM: Total flavones of Hippophae rhamnoides L. (TFH) have a clinical use in the
      treatment of cardiac disease. The pharmacological effects of TFH are attributed
      to its major flavonoid components, isorhamnetin, kaempferol, and quercetin.
      However, poor oral bioavailability of these flavonoids limits the clinical
      applications of TFH. This study explores phytic acid (IP6) enhancement of the
      oral absorption in rats of isorhamnetin, kaempferol, and quercetin in TFH.
      METHODS: In vitro Caco-2 cell experiments and in vivo pharmacokinetic studies
      were performed to investigate the effects of IP6. The aqueous solubility and
      lipophilicity of isorhamnetin, quercetin, and kaempferol were determined with and
      without IP6, and mucosal epithelial damage resulting from IP6 addition was
      evaluated by MTT assays and morphology observations. RESULTS: The Papp of
      isorhamnetin, kaempferol, and quercetin was improved 2.03-, 1.69-, and 2.11-fold
      in the presence of 333 MUg/mL of IP6, respectively. Water solubility was
      increased 22.75-, 15.15-, and 12.86-fold for isorhamnetin, kaempferol, and
      quercetin, respectively, in the presence of 20mg/mL IP6. The lipophilicity of the
      three flavonoids was slightly decreased, but their hydrophilicity was increased
      after the addition of IP6 in the water phase as the logP values of isorhamnetin,
      kaempferol, and quercetin decreased from 2.38+/-0.12 to 1.64+/-0.02, from 2.57+/
      0.20 to 2.01+/-0.04, and from 2.39+/-0.12 to 1.15+/-0.01, respectively. The
      absorption enhancement ratios were 3.21 for isorhamnetin, 2.98 for kaempferol,
      and 1.64 for quercetin with co-administration of IP6 (200 mg/kg) in rats. In
      addition, IP6 (200 mg/kg, oral) caused neither significant irritation to the rat
      intestines nor cytotoxicity (400 MUg/mL) in Caco-2 cells. CONCLUSIONS: The oral
      bioavailability of isorhamnetin, kaempferol, and quercetin in TFH was enhanced by
      the co-administration of IP6. The main mechanisms are related to their enhanced
      aqueous solubility and permeability in the presence of IP6. In summary, IP6 is a
      potential absorption enhancer for pharmaceutical formulations that is both
      effective and safe.

PMID- 24462959
TI  - New lignans from the bioactive fraction of Sambucus williamsii Hance and
      proliferation activities on osteoblastic-like UMR106 cells.
AB  - Four new lignans (1, 7-9), together with nine known ones, were isolated from the
      anti-osteoporosis fraction of the extract of Sambucus williamsii Hance which was
      eluted by 50% and 95% aqueous ethanol over D101 macroporous resin column. Their
      structures were elucidated by NMR spectroscopic analyses, and the absolute
      configurations of all compounds were determined by application of circular
      dichroism method. All the compounds were reported for the first time from the
      Sambucus genus and firstly studied for their proliferation effects on
      osteoblastic-like UMR 106 cell. The data showed that compounds 2-9 significantly
      promoted cell proliferation in some dose, especially compounds 2, 3, 4, 5, and 7
      increased osteoblastic cell numbers by 31.3%, 28.3%, 25.6%, 25.1% and 26.0% at
      10(-10) M, 10(-10) M, 10(-7) M, 10(-10) M and 10(-10) M, respectively, which
      suggested that lignans were the components accounting for the bone protective
      effects of SWH.

PMID- 24462960
TI  - Intravenous salt supplementation with low-dose furosemide for treatment of acute
      decompensated heart failure.
AB  - BACKGROUND: Theoretically, salt supplementation should promote diuresis through
      increasing the glomerular filtration rate (GFR) during treatment of acute
      decompensated heart failure (ADHF) even with low-dose furosemide; however, there
      is little evidence to support this idea. METHODS AND RESULTS: This was a
      prospective, randomized, open-label, controlled trial that compared the diuretic
      effectiveness of salt infusion with that of glucose infusion supplemented with
      low-dose furosemide in 44 consecutive patients with ADHF. Patients were randomly
      administered 1.7% hypertonic saline solution supplemented with 40 mg furosemide
      (salt infusion group) or glucose supplemented with 40 mg furosemide (glucose
      infusion group). Our major end points were 24-hour urinary volume and GFR.
      Urinary volume was greater in the salt infusion group than in the glucose
      infusion group (2,701 +/- 920 vs 1,777 +/- 797 mL; P < .001). There was no
      significant difference in the estimated GFR at baseline. Creatinine clearance for
      24 h was greater in the salt infusion group than in the glucose infusion group
      (63.5 +/- 52.6 vs 39.0 +/- 26.3 mL min(-1) 1.73 m(-2); P = .048). CONCLUSIONS:
      Salt supplementation rather than salt restriction evoked favorable diuresis
      through increasing GFR. The findings support an efficacious novel approach of the
      treatment of ADHF.

PMID- 24462961
TI  - New advances in mucosal vaccination.
AB  - The ICI 2013 Mucosal Vaccine Workshop presentations covered a wide range of
      topics, these mainly fell into three categories: (i) Understanding the
      interactions of host and microbes, specifically commensal pathogens and improving
      the antigen uptake via the (microfold cells) M cells to induce effective IgA
      antibody immunity at the gut mucosa; (ii) effective plant-based vaccines and
      (iii) development of prophylactic and therapeutic mucosal-based vaccine
      strategies for virus infections such as human immunodeficiency virus (HIV),
      influenza and human papillomavirus (HPV) associated head and neck cancers. How to
      improve the efficacy of oral vaccines, novel intranasal mucosal adjuvants and a
      unique intra-cheek delivery method were also discussed. Presenters emphasized the
      differences associated with systemic and mucosal vaccination, specifically, how
      mucosal vaccines unlike systemic delivery can induce effective immunity at the
      first line of defence. Collectively, the workshop provided insights into recent
      developments in the mucosal vaccine research field, highlighting the complexities
      associated with designing safe and effective mucosal vaccines. 

PMID- 24462962
TI  - Social cognition and neural substrates of face perception: implications for
      neurodevelopmental and neuropsychiatric disorders.
AB  - BACKGROUND: Social cognition is an important aspect of social behavior in humans.
      Social cognitive deficits are associated with neurodevelopmental and
      neuropsychiatric disorders. In this study we examine the neural substrates of
      social cognition and face processing in a group of healthy young adults to
      examine the neural substrates of social cognition. METHODS: Fifty-seven
      undergraduates completed a battery of social cognition tasks and were assessed
      with electroencephalography (EEG) during a face-perception task. A subset (N=22)
      were administered a face-perception task during functional magnetic resonance
      imaging. RESULTS: Variance in the N170 EEG was predicted by social attribution
      performance and by a quantitative measure of empathy. Neurally, face processing
      was more bilateral in females than in males. Variance in fMRI voxel count in the
      face-sensitive fusiform gyrus was predicted by quantitative measures of social
      behavior, including the Social Responsiveness Scale (SRS) and the Empathizing
      Quotient. CONCLUSIONS: When measured as a quantitative trait, social behaviors in
      typical and pathological populations share common neural pathways. The results
      highlight the importance of viewing neurodevelopmental and neuropsychiatric
      disorders as spectrum phenomena that may be informed by studies of the normal
      distribution of relevant traits in the general population.

PMID- 24462964
TI  - Lack of genotoxic potential of ZnO nanoparticles in in vitro and in vivo tests.
AB  - The industrial application of nanotechnology, particularly using zinc oxide
      (ZnO), has grown rapidly, including products such as cosmetics, food, rubber,
      paints, and plastics. However, despite increasing population exposure to ZnO, its
      potential genotoxicity remains controversial. The biological effects of
      nanoparticles depend on their physicochemical properties. Preparations with well
      defined physico-chemical properties and standardized test methods are required
      for assessing the genotoxicity of nanoparticles. In this study, we have evaluated
      the genotoxicity of four kinds of ZnO nanoparticles: 20nm and 70nm size,
      positively or negatively charged. Four different genotoxicity tests (bacterial
      mutagenicity assay, in vitro chromosomal aberration test, in vivo comet assay,
      and in vivo micronucleus test, were conducted, following Organization for
      Economic Cooperation and Development (OECD) test guidelines with good laboratory
      practice (GLP) procedures. No statistically significant differences from the
      solvent controls were observed. These results suggest that surface-modified ZnO
      nanoparticles do not induce genotoxicity in in vitro or in vivo test systems. 

PMID- 24462963
TI  - Effects of amphetamine exposure in adolescence or young adulthood on inhibitory
      control in adult male and female rats.
AB  - Heightened impulsivity is a feature of some psychiatric disorders, including
      addiction, that also have sex-specific patterns of expression. The relationship
      between addiction and impulsivity may be driven by drug-induced changes in
      behavior caused by long term adaptations in signaling within the medial
      prefrontal cortex (mPFC). Here, we used a response inhibition task that is
      sensitive to changes in mPFC function to examine the effects of sex and exposure
      to amphetamine (AMPH) on impulsive action and vigilance. We also examined drug
      induced alterations in glutamatergic and dopaminergic signaling through challenge
      injections with the NMDA receptor antagonist MK-801 (dizocilpine) and AMPH. Male
      and female Sprague Dawley rats were injected (i.p.) with saline or 3 mg/kg AMPH
      every other day during adolescence (postnatal day (P) 27-45) or adulthood (P85
      103). Starting on P125-135, rats were tested for their ability to lever press for
      a food reward during periods of signaled availability and withhold responding
      during a "premature response" phase. In experiment 1, rats received challenge
      injections (i.p.) of MK-801 and AMPH followed by tests of task performance and
      locomotor activity. In experiment 2, rats received intra-mPFC infusion of MK-801.
      We found that females had better inhibitory control and poorer vigilance than
      males and that AMPH exposure had both sex- and age-of-exposure dependent effects
      on impulsivity. Systemic drug challenges disrupted task performance, particularly
      in females, and increased impulsivity while intra-mPFC infusions had modest
      effects. AMPH exposure did not affect responses to drug challenges. Together,
      these results suggest that sex mediates both trait and drug-induced impulsivity.

PMID- 24462965
TI  - Maternal-fetal-infant dynamics of the C3-epimer of 25-hydroxyvitamin D.
AB  - BACKGROUND: Poor vitamin D status (i.e. low serum 25-hydroxyvitamin D (25(OH)D))
      has been associated with adverse clinical outcomes during pregnancy and
      childhood. However, the interpretation of serum 25(OH)D levels may be complicated
      by the presence of the C3-epimer of 25(OH)D. We aimed to quantify C3-epi-25(OH)D3
      in pregnant women and fetuses, to explore the relationship of the C3-epimer
      between maternal and cord samples, and to establish whether infant C3-epimer
      abundance is explained by prenatal formation. METHODS: In a sub-study of a
      randomized trial of prenatal vitamin D3, 25(OH)D3 and C3-epi-25(OH)D3 were
      quantified by LC-MS/MS in 71 sets of mother-fetus-infant serum samples, including
      maternal delivery specimens, cord blood, and infant specimens acquired at 3-28
      weeks of age. RESULTS: Without supplementation, median concentrations of C3-epi
      25(OH)D3 were higher in infants (6.80 nmol/L) than mothers (0.45 nmol/L) and cord
      blood (0 nmol/L). However, there was substantial variation such that C3-epi
      25(OH)D3 accounted for up to 11% (maternal), 14% (cord), and 25% (infant) of the
      total 25(OH)D3. Supplemental vitamin D3 significantly increased maternal-fetal C3
      epi-25(OH)D3, and was a preferential source of C3-epi-25(OH)D3 compared to basal
      vitamin D, possibly due to C3-epi-cholecalciferol in the supplement. Multivariate
      regression did not suggest transplacental transfer of C3-epi-25(OH)D3, but rather
      indicated its generation within the fetal-placental unit from maternally-derived
      25(OH)D3. Neither maternal nor fetal C3-epi-25(OH)D3 is accounted for the
      relatively high concentrations of infant C3-epi-25(OH)D3, suggesting rapid
      postnatal generation. CONCLUSIONS: C3-epi-25(OH)D3 is present in some pregnant
      women and fetuses, but does not appear to be efficiently transferred
      transplacentally. High C3-epimer concentrations in infancy are probably due to
      postnatal formation rather than fetal stores.

PMID- 24462966
TI  - Down syndrome screening: suitability of a WHO 5 standardized total hCG assay.
AB  - OBJECTIVE: To determine how the adoption of the new WHO 5th International
      Standard (IS 07/364) will affect the suitability of total betahCG as a marker for
      second trimester Down syndrome screening, compared to the current WHO 3rd IS
      (75/537). DESIGN AND METHODS: Assays employing both standards were evaluated on
      the Beckman Coulter DxI platform. Matched betahCG results from 232 fresh second
      trimester maternal serum samples were compared. In addition, stored samples from
      51 Down syndrome and 251 matched control sera were also tested with both assays
      and results converted to weight-adjusted multiples of the median (MoMs). These
      results were combined with maternal age and the existing alpha-fetoprotein,
      unconjugated estriol and inhibin-A MoM levels to compute patient-specific Down
      syndrome risk. RESULTS: Correlation between the two sets of results on fresh
      samples was high (r=0.993), but showed a proportional increase of 33% (95% CI 31%
      to 35%) in results using the new versus old assay across the range of
      measurements. betahCG results in the case/control dataset were also highly
      correlated (0.994) and showed a similar proportional increase (34%). After
      computing assay-specific MoMs, the resulting 'triple' and 'quadruple' Down
      syndrome risks were highly correlated, and resulted in no difference in either of
      the two detection rates (78% and 88%, respectively) or false positive rates
      (6.4%, 6.8%). CONCLUSIONS: Laboratories using the DxI platform with the new total
      betahCG 5th IS assay will need to compute new reference (medians), but can expect
      no impact on the clinical validity of the associated Down syndrome screening
      programs.

PMID- 24462967
TI  - Human chorionic gonadotropin and alpha-fetoprotein in cerebral spinal fluid:
      method validation and retrospective review.
AB  - OBJECTIVE: Measurement of human chorionic gonadotropin (hCG) and alpha
      fetoprotein (AFP) in cerebrospinal fluid (CSF) can aid in the diagnosis of germ
      cell tumors (GCTs). Matrix effects can influence test results when alternative
      sample types are used, therefore, alternative sample types should always be
      validated before clinical use. Here we have validated the Advia(r) Centaur total
      hCG and AFP methods for use with CSF. We also performed a retrospective review of
      5years of CSF hCG and AFP measurements sent out from our institution. DESIGN AND
      METHODS: Both hCG and AFP concentrations were measured using the ADVIA Centaur(r)
      total hCG or AFP assay. RESULTS: The Centaur hCG and AFP assays, performed on
      CSF, had intra- and inter-assay imprecisions <10.2% CV. The assays were linear
      over a dynamic range of 10-1000IU/L for hCG and 10-1000MUg/L for AFP.
      Retrospective chart review confirmed that GCTs have a male predominance and are
      diagnosed most frequently in the second decade of life. The data also illustrate
      the importance of measuring both serum and CSF concentrations as CSF can be
      elevated in the absence of serum elevations. CONCLUSIONS: The Centaur total hCG
      and AFP methods accurately quantify hCG and AFP in CSF.

PMID- 24462968
TI  - Identification of the centromere-specific histone H3 variant in Lotus japonicus.
AB  - The centromere is a structurally and functionally specialized region present on
      every eukaryotic chromosome. Lotus japonicus is a model legume species for which
      there is very limited information on the centromere structure. Here we cloned and
      characterized the L. japonicus homolog of the centromere-specific histone H3 gene
      (LjCenH3) encoding a 159-amino acid protein. Using an Agrobacterium-based
      transformation system, LjCenH3 tagged with a green fluorescent protein was
      transferred into L. japonicus cells. The centromeric position of LjCENH3 protein
      was revealed on L. japonicus metaphase chromosomes by an immunofluorescence
      assay. The identification of LjCenH3 as a critical centromere landmark could pave
      the way for a better understanding of centromere structure in this model and
      other agriculturally important legume species. 

PMID- 24462969
TI  - Deep sequencing of the Camellia chekiangoleosa transcriptome revealed candidate
      genes for anthocyanin biosynthesis.
AB  - Camellia chekiangoleosa is an important species of genus Camellia. It provides
      high-quality edible oil and has great ornamental value. The flowers are big and
      red which bloom between February and March. Flower pigmentation is closely
      related to the accumulation of anthocyanin. Although anthocyanin biosynthesis has
      been studied extensively in herbaceous plants, little molecular information on
      the anthocyanin biosynthesis pathway of C. chekiangoleosa is yet known. In the
      present study, a cDNA library was constructed to obtain detailed and general data
      from the flowers of C. chekiangoleosa. To explore the transcriptome of C.
      chekiangoleosa and investigate genes involved in anthocyanin biosynthesis, a 454
      GS FLX Titanium platform was used to generate an EST dataset. About 46,279
      sequences were obtained, and 24,593 (53.1%) were annotated. Using Blast search
      against the AGRIS, 1740 unigenes were found homologous to 599 Arabidopsis
      transcription factor genes. Based on the transcriptome dataset, nine anthocyanin
      biosynthesis pathway genes (PAL, CHS1, CHS2, CHS3, CHI, F3H, DFR, ANS, and UFGT)
      were identified and cloned. The spatio-temporal expression patterns of these
      genes were also analyzed using quantitative real-time polymerase chain reaction.
      The study results not only enrich the gene resource but also provide valuable
      information for further studies concerning anthocyanin biosynthesis. 

PMID- 24462970
TI  - Relational memory generalization and integration in a transitive inference task
      with and without instructed awareness.
AB  - Two experiments investigated the potential facilitative effects of prior
      instructed awareness and predetermined learning criteria on humans' ability to
      make transitive inference (TI) judgments. Participants were first exposed to a
      learning phase and required to learn five premise pairs (A+B-, B+C-, C+D-, D+E-,
      E+F-). Testing followed, where participants made judgments on novel non-endpoint
      (BD, BE and CE) and endpoint inferential pairs (AC, AD, AE, AF, BF, CF and DF),
      as well as learned premise pairs. Across both experiments, one group were made
      aware that the stimuli could be arranged in a hierarchy, while another group were
      not given this instruction. Results demonstrated that prior instructional task
      awareness led to a minor performance advantage, but that this difference was not
      significant. Furthermore, in Experiment 2, inferential test trial accuracy was
      not correlated with a post-experimental measure of awareness. Thus, the current
      findings suggest that successful TI task performance may occur in the absence of
      awareness, and that repeated exposure to learning and test phases may allow weak
      inferential performances to emerge gradually. Further research and alternative
      methods of measuring awareness and its role in TI are needed. 

PMID- 24462971
TI  - Exposure studies of core-shell Fe/Fe(3)O(4) and Cu/CuO NPs to lettuce (Lactuca
      sativa) plants: Are they a potential physiological and nutritional hazard?
AB  - Iron and copper nanomaterials are widely used in environmental remediation and
      agriculture. However, their effects on physiological parameters and nutritional
      quality of terrestrial plants such as lettuce (Lactuca sativa) are still unknown.
      In this research, 18-day-old hydroponically grown lettuce seedlings were treated
      for 15 days with core-shell nanoscale materials (Fe/Fe(3)O(4), Cu/CuO) at 10 and
      20mg/L, and FeSO(4).7H(2)O and CuSO(4).5H(2)O at 10mg/L. At harvest, Fe, Cu,
      micro and macronutrients were determined by ICP-OES. Also, we evaluated
      chlorophyll content, plant growth, and catalase (CAT) and ascorbate peroxidase
      (APX) activities. Our results showed that iron ions/NPs did not affect the
      physiological parameters with respect to water control. Conversely, Cu ions/NPs
      reduced water content, root length, and dry biomass of the lettuce plants. ICP
      OES results showed that nano-Cu/CuO treatments produced significant accumulation
      of Cu in roots compared to the CuSO(4).5H(2)O treatment. In roots, all Cu
      treatments increased CAT activity but decreased APX activity. In addition,
      relative to the control, nano-Cu/CuO altered the nutritional quality of lettuce,
      since the treated plants had significantly more Cu, Al and S but less Mn, P, Ca,
      and Mg.

PMID- 24462972
TI  - Determination of critical factors causing cytotoxicity in the virus
      neutralization test.
AB  - The fluorescent antibody virus neutralization (FAVN) test, an international
      standard method for serological testing for rabies, has been adopted by many
      countries. However, some dog serum samples inhibit the formation of cell
      monolayers by BHK-21 cells used in the test, resulting in failures to determine
      antibody titers. This inhibition of cell monolayer formation was defined as
      cytotoxicity. In this study, critical factors that induce cytotoxicity of the dog
      serum in BHK-21 cells were determined, and the effective ways to prevent
      cytotoxicity were also established. Specifically, some anticoagulants, anti-BHK
      21 cell IgG antibodies, and serum storage at temperatures of >25 degrees C were
      found to induce cytotoxicity. On the other hand, several treatments of the dog
      serum, including the absorption by BHK-21 cells or kaolin, incubation with
      trypsin-EDTA, and the use of collagen- or gelatin-coated plates, were shown to
      reduce cytotoxicity. Based on these results, the FAVN test may be modified to
      enhance its performance. 

PMID- 24462973
TI  - Development and characterization of monoclonal antibody against non-structural
      protein-2 of Chikungunya virus and its application.
AB  - The recent epidemics of Chikungunya viruses (CHIKV) with unprecedented magnitude
      and unusual clinical severity have raised a great public health concern
      worldwide, especially due to unavailability of vaccine or specific therapy. This
      emphasizes the need to understand the biological processes of this virus in
      details. Although CHIKV associated research has been initiated, the availability
      of CHIKV specific reagents for in-depth investigation of viral infection and
      replication are scanty. For Alphavirus replication, non-structural protein 2
      (nsP2) is known to play a key regulatory role among all other non-structural
      proteins. The current study describes the development and characterization of
      nsP2 specific monoclonal antibody (mAb) against a synthetic peptide of CHIKV.
      Reactivity and efficacy of this mAb have been demonstrated by ELISA, Western
      blot, Flow cytometry and Immunofluorescence assay. Time kinetic study confirms
      that this mAb is highly sensitive to CHIKV-nsP2 as this protein has been detected
      very early during viral replication in infected cells. Homology analysis of the
      selected epitope sequence reveals that it is conserved among all the CHIKV
      strains of different genotypes, while analysis with other Alphavirus sequences
      shows that none of them are 100% identical to the epitope sequence. Moreover,
      using the mAb, three isoforms of CHIKV-nsP2 have been detected in 2D blot
      analysis during infection in mammalian cells. Accordingly, it can be suggested
      that the mAb reported in this study can be a sensitive and specific tool for
      experimental investigations of CHIKV replication and infection. 

PMID- 24462974
TI  - An efficient tool for random insertional mutagenesis: Agrobacterium tumefaciens
      mediated transformation of the filamentous fungus Aspergillus terreus.
AB  - Agrobacterium tumefaciens-mediated transformation (ATMT) has been widely used in
      various organisms. In the current study, we developed a simple and efficient
      system for genetic transformation of the filamentous fungus Aspergillus terreus
      using ATMT. The transformation protocol was optimized for certain parameters to
      rapidly generate a library of Transferred DNA (T-DNA) insertion mutants of A.
      terreus. The presence of mitotically stable hygromycin resistance gene (hph)
      integration in the genome was confirmed by PCR, and T-DNA flanking sequences were
      cloned by thermal asymmetric interlaced PCR. The successful construction of the
      mutant library demonstrated the utility of the ATMT approach for future forward
      and reverse genetic studies in this important fungus. 

PMID- 24462975
TI  - Improving the efficiency of plasmid transformation in Shewanella oneidensis MR-1
      by removing ClaI restriction site.
AB  - Here we demonstrate that elimination of ClaI restriction site from the sequence
      of a plasmid DNA increases the efficiency of transformation of Shewanella
      oneidensis MR-1 significantly. To achieve reliable transformation of S.
      oneidensis MR-1 plasmids either lacking ClaI site or isolated from primary
      transformants of S. oneidensis should be used. 

PMID- 24462976
TI  - Racial bias in pain perception and response: experimental examination of
      automatic and deliberate processes.
AB  - Racial disparities in pain treatment pose a significant public health and
      scientific problem. Prior studies have demonstrated that clinicians and
      nonclinicians are less perceptive of, and suggest less treatment for, the pain of
      African Americans relative to European Americans. Here we investigate the effects
      of explicit/implicit patient race presentation, patient race, and perceiver race
      on pain perception and response. African American and European American
      participants rated pain perception, empathy, helping motivation, and treatment
      suggestion in response to vignettes about patients' pain. Vignettes were
      accompanied by a rapid (implicit) or static (explicit) presentation of an African
      or European American patient's face. Participants perceived and responded more to
      European American patients in the implicit prime condition, when the effect of
      patient race was below the level of conscious regulation. This effect was
      reversed when patient race was presented explicitly. Additionally, female
      participants perceived and responded more to the pain of all patients, relative
      to male participants, and in the implicit prime condition, African American
      participants were more perceptive and responsive than European Americans to the
      pain of all patients. Taken together, these results suggest that known
      disparities in pain treatment may be largely due to automatic (below the level of
      conscious regulation) rather than deliberate (subject to conscious regulation)
      biases. These biases were not associated with traditional implicit measures of
      racial attitudes, suggesting that biases in pain perception and response may be
      independent of general prejudice. PERSPECTIVE: Results suggest that racial biases
      in pain perception and treatment are at least partially due to automatic
      processes. When the relevance of patient race is made explicit, however, biases
      are attenuated and even reversed. We also find preliminary evidence that African
      Americans may be more sensitive to the pain of others than are European
      Americans.

PMID- 24462977
TI  - Analysis of maternal-zygotic ugdh mutants reveals divergent roles for HSPGs in
      vertebrate embryogenesis and provides new insight into the initiation of left
      right asymmetry.
AB  - Growth factors and morphogens regulate embryonic patterning, cell fate
      specification, cell migration, and morphogenesis. The activity and behavior of
      these signaling molecules are regulated in the extracellular space through
      interactions with proteoglycans (Bernfield et al., 1999; Perrimon and Bernfield
      2000; Lander and Selleck 2000; Selleck 2000). Proteoglycans are high molecular
      weight proteins consisting of a core protein with covalently linked
      glycosaminoglycan (GAG) side chains, which are thought to mediate ligand
      interaction. Drosophila mutant embryos deficient for UDP-glucose dehydrogenase
      activity (Ugdh, required for GAG synthesis) exhibit abnormal Fgf, Wnt and TGFbeta
      signaling and die during gastrulation, indicating a broad and critical role for
      proteoglycans during early embryonic development (Lin et al., 1999; Lin and
      Perrimon 2000) (Hacker et al., 1997). Mouse Ugdh mutants also die at
      gastrulation, however, only Fgf signaling appears disrupted (Garcia-Garcia and
      Anderson, 2003). These findings suggested a possible divergence in the
      requirement for proteoglycans during Drosophila and mouse embryogenesis, and that
      mammals may have evolved alternative means of regulating Wnt and TGFbeta
      activity. To further examine the function of proteoglycans in vertebrate
      development, we have characterized zebrafish mutants devoid of both maternal and
      zygotic Ugdh/Jekyll activity (MZjekyll). We demonstrate that MZjekyll mutant
      embryos display abnormal Fgf, Shh, and Wnt signaling activities, with concomitant
      defects in central nervous system patterning, cardiac ventricular fate
      specification and axial morphogenesis. Furthermore, we uncover a novel role for
      proteoglycans in left-right pattern formation. Our findings resolve longstanding
      questions into the evolutionary conservation of Ugdh function and provide new
      mechanistic insights into the initiation of left-right asymmetry. 

PMID- 24462978
TI  - Circulating extracellular vesicles as a potential source of new biomarkers of
      drug-induced liver injury.
AB  - Like most cell types, hepatocytes constantly produce extracellular vesicles (EVs)
      such as exosomes and microvesicles that are released into the circulation to
      transport signaling molecules and cellular waste. Circulating EVs are being
      vigorously explored as biomarkers of diseases and toxicities, including drug
      induced liver injury (DILI). Emerging data suggest that (a) blood-borne EVs
      contain liver-specific mRNAs and microRNAs (miRNAs), (b) the levels can be
      remarkably elevated in response to DILI, and (c) the increases correlate well
      with classical measures of liver damage. The expression profile of mRNAs in EVs
      and the compartmentalization of miRNAs within EVs or other blood fractions were
      found to be indicative of the offending drug involved in DILI, thus providing
      more informative assessment of liver injury than using alanine aminotransferase
      alone. EVs in the urine and cell culture medium were also found to contain
      proteins or mRNAs that were indicative of DILI. However, major improvements in EV
      isolation methods are needed for the discovery, evaluation, and quantification of
      possible DILI biomarkers in circulating EVs. 

PMID- 24462979
TI  - Continuous cadmium exposure from weaning to maturity induces downregulation of
      ovarian follicle development-related SCF/c-kit gene expression and the
      corresponding changes of DNA methylation/microRNA pattern.
AB  - Cadmium (Cd) impairs ovary structure and function in mature animals. However, the
      influence of Cd on follicle development from weaning to maturity is obscure. In
      the current study, 21-day-old Wistar rats were administered Cd chloride at doses
      of 0, 0.5, 2.0 and 8.0 mg/kg body weight once a day for eight weeks by gavage.
      After administration, a significant decrease in ovarian wet weight, ovarian/body
      weight ratios, and primordial follicles, in addition to an increase in atresic
      follicles, were observed. Transmission electron microscopy and TUNEL assay
      confirmed the increase of follicle apoptosis as Cd concentration increased. Real
      time quantitative PCR and Western blotting showed a significantly decreased
      expression of follicle development-related factors, stem cell factor (SCF) and c
      kit. Bisulfite sequencing suggested that the total methylation percentages of
      SCF/c-kit promoter region were not obvious change after Cd exposure. Real-time
      quantitative PCR revealed a significantly increased expression of miR-193, miR
      221 and miR-222, which regulate c-kit, in the 2.0 mg/kg and 8.0 mg/kg treatment
      groups. Overall, this study proved that Cd administration from weaning to
      maturity could damage follicle development, suggesting that SCF/c-kit might play
      an important role in this effect. In addition, microRNAs might play a role in c
      kit protein downregulation.

PMID- 24462980
TI  - Sustained donor engraftment in recipients of double-unit cord blood
      transplantation is possible despite donor-specific human leukoctye antigen
      antibodies.
AB  - The impact of human leukocyte antigen (HLA) donor-specific antibodies (DSA) on
      cord blood (CB) engraftment is controversial. We evaluated the influence of pre
      existing HLA-antibodies (HLA-Abs) on engraftment in 82 double-unit CB recipients
      (median age, 48 years) who underwent transplantation for hematologic
      malignancies. Of 28 patients (34%) with HLA-Abs, 12 had DSA (median mean
      fluorescence intensity 5255; range, 1057 to 9453). DSA patients had acute
      leukemia (n = 11) or myelodysplasia (n = 1) and all received either high-dose or
      reduced-intensity (but myeloablative) conditioning. After myeloablative CB
      transplantation (CBT) (n = 67), sustained donor engraftment was observed in 95%
      without HLA-Abs (median, 23 days), 100% with nonspecific HLA-Abs (median, 23
      days), and 92% with DSA (median, 31 days, P = .48). Of 6 patients with HLA-Abs to
      1 unit, 3 engrafted with that unit and 3 with the other. Of 6 patients with HLA
      Abs against both units, 1 had graft failure despite being 100% donor, and 5
      engrafted with 1 unit. Successful donor engraftment is possible in patients with
      DSA after myeloablative double-unit CBT. Our data suggest potential deleterious
      effects of DSA can be abrogated in patients with hematologic malignancies.

PMID- 24462981
TI  - Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the
      reconstituting T cell compartment long-term after hematopoietic stem cell
      transplantation.
AB  - Human cytomegalovirus (CMV) reactivation frequently occurs during the early phase
      of immune recovery after allogeneic hematopoietic stem cell transplantation
      (HSCT). Whereas the recovery of virus-specific immunity in the early phase after
      HSCT is extensively studied, the impact of CMV on the reconstitution and
      composition of the T cell compartment long-term after HSCT is unknown. We
      analyzed T cell reconstitution 1 to 2 years after HSCT in 131 pediatric patients.
      One year after HSCT, patients with early CMV reactivation (n = 46) had 3-fold
      higher CD8(+) T cell numbers (median, 1323 versus 424 cells/MUL; P < .0001)
      compared with patients without CMV reactivation (n = 85). This effect, caused by
      a major expansion of CD8(+) effector memory (EM) and end-stage effector (EMRA) T
      cells, was independent of pretransplantation donor and recipient CMV serostatus
      and not seen after Epstein-Barr virus or adenovirus reactivations. At 1 and 2
      years after HSCT, the absolute numbers of CD8(+) naive and central memory T
      cells, as well as CD4(+) naive, CM, EM, and EMRA T cells, did not differ between
      patients with or without CMV reactivation. In the second year after HSCT, a
      significant contraction of the initially expanded CD8(+) EM and EMRA T cell
      compartments was observed in patients with early CMV reactivation. In conclusion,
      CMV reactivation early after pediatric HSCT leaves a specific and dynamic imprint
      on the size and composition of the CD8(+) T cell compartment without compromising
      the reconstitution of CD8(+) and CD4(+) naive and central memory T cells pivotal
      in the response to neo and recall antigens.

PMID- 24462982
TI  - Antithymocyte globulin before allogeneic stem cell transplantation for
      progressive myelodysplastic syndrome: a study from the French Society of Bone
      Marrow Transplantation and Cellular Therapy.
AB  - We investigated the impact of rabbit antithymocyte globulins (ATG) on patient
      outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive
      myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent
      allo-SCT for progressive MDS between October 1999 and December 2009, 93 received
      ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no
      ATG group). Donors were sibling (n = 153) or HLA-matched unrelated (n = 89).
      Patients received blood (n = 90) or marrow (n = 152) grafts after either
      myeloablative (n = 109) or reduced-intensity (n = 133) conditioning. Three-year
      overall and event-free survival, nonrelapse mortality, relapse, and chronic graft
      versus-host disease (GVHD) development were not significantly different between
      the 2 groups. In contrast, acute grade II to IV GVHD occurred more often in the
      no-ATG group (55% of the patients) than in the ATG group (27%, P < .0001).
      Similar results were observed with acute grade III to IV GVHD (28% and 14% in the
      no-ATG group and ATG group, respectively; P = .009). In multivariate analysis,
      after adjustment with propensity score, the absence of ATG was the strongest
      parameter associated with an increased risk of acute grade II to IV GVHD (hazard
      ratio, 2.13; 95% confidence interval, 1.35 to 3.37; P = .001]. ATG had no impact
      on overall and event-free survival or cumulative incidence of the relapse. In
      conclusion, the addition of ATG to allo-SCT conditioning did not increase the
      incidence of relapse of patients with progressive MDS. The incidence of acute
      GVHD was decreased without compromising outcomes.

PMID- 24462983
TI  - HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell
      transplantation in children with Fanconi anemia.
AB  - We report the outcome of 12 consecutive pediatric patients with Fanconi anemia
      (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor
      and who were given T cell-depleted, CD34(+) positively selected cells from a
      haploidentical related donor after a reduced-intensity, fludarabine-based
      conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the
      cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5%
      to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus
      host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%),
      respectively. The conditioning regimen was well tolerated, with no fatal regimen
      related toxicity and 3 cases of grade III regimen-related toxicity. The
      cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%).
      The 5-year overall survival, event-free survival, and disease-free survival were
      83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to
      100%), respectively. These data demonstrate that a fludarabine-based conditioning
      regimen, followed by infusion of high doses of T cell-depleted stem cells, is
      able to ensure engraftment with good overall survival and disease-free survival,
      confirming the feasibility of haploidentical hematopoietic stem cell
      transplantation in FA. To the best of our knowledge, this is the largest series
      of hematopoietic stem cell transplantation from a haploidentical related donor in
      FA patients reported to date.

PMID- 24462984
TI  - BK virus disease after allogeneic stem cell transplantation: a cohort analysis.
AB  - The clinical epidemiology of BK virus (BKV) disease after allogeneic
      hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated
      491 patients transplanted from January 2010 to December 2011 at a single
      transplant center to assess incidence, severity, and risk factors for BKV disease
      after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in
      association with genitourinary symptoms without other concurrent genitourinary
      conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of
      .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was
      considered severe in 27 patients (5.5%). In multivariate Cox modeling, time
      dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted
      hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95%
      CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to
      5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to
      3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III
      to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI,
      1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease
      is common and is associated with significant and prolonged morbidity after HSCT.
      Prospective studies are needed to better define the morbidity of post-HSCT BKV
      disease and inform the design of prophylaxis and treatment trials. 

PMID- 24462985
TI  - Chlorogenic acid increased acrylamide formation through promotion of HMF
      formation and 3-aminopropionamide deamination.
AB  - This research was aimed to investigate why chlorogenic acid, presents at high
      concentrations in some food raw material, influences acrylamide formation. In the
      asparagine/glucose Maillard reaction system (pH=6.8), addition of chlorogenic
      acid significantly increased acrylamide formation and inhibited its elimination.
      In contrast, the quinone derivative of chlorogenic acid decreased acrylamide
      formation. Three mechanisms may be involved for increasing acrylamide formation
      by chlorogenic acid. Firstly, it increased the formation of HMF, which acts as a
      more efficient precursor than glucose to form acrylamide. Secondly, it decreased
      activation energy for conversion of 3-aminopropionamide (3-APA) to acrylamide
      (from 173.2 to 136.6kJ/mol), and enhances deamination from 3-APA. And thirdly, it
      prevented attack of the produced acrylamide from free radicals by keeping high
      redox potential during the Maillard reaction. 

PMID- 24462986
TI  - Degradation of 1-hydroxy-2,4-dinitrobenzene from aqueous solutions by
      electrochemical oxidation: role of anodic material.
AB  - Electrochemical oxidation (ECOx) of 1-hydroxy-2,4-dinitrobenzene (or 2,4
      dinitrophenol: 2,4-DNP) in aqueous solutions by electrolysis under galvanostatic
      control was studied at Pb/PbO2, Ti/SnO2, Ti/IrxRuySnO2 and Si/BDD anodes as a
      function of current density applied. Oxidative degradation of 2,4-DNP has clearly
      shown that electrode material and the current density applied were important
      parameters to optimize the oxidation process. It was observed that 2,4-DNP was
      oxidized at few substrates to CO2 with different results, obtaining good removal
      efficiencies at Pb/PbO2, Ti/SnO2 and Si/BDD anodes. Trends in degradation way
      depend on the production of hydroxyl radicals (OH) on these anodic materials, as
      confirmed in this study. Furthermore, HPLC results suggested that two kinds of
      intermediates were generated, polyhydroxylated intermediates and carboxylic
      acids. The formation of these polyhydroxylated intermediates seems to be
      associated with the denitration step and substitution by OH radicals on aromatic
      rings, this being the first proposed step in the reaction mechanism. These
      compounds were successively oxidized, followed by the opening of aromatic rings
      and the formation of a series of carboxylic acids which were at the end oxidized
      into CO2 and H2O. On the basis of these information, a reaction scheme was
      proposed for each type of anode used for 2,4-D oxidation. 

PMID- 24462987
TI  - Dichloromethane removal and microbial variations in a combination of UV
      pretreatment and biotrickling filtration.
AB  - Biofiltration of hydrophobic and/or recalcitrant volatile organic compounds in
      industry is currently limited. A laboratory-scale system integrating ultraviolet
      (UV) photodegradation and a biotrickling filter (BTF) was developed to treat
      dichloromethane (DCM), and this was compared to BTF alone. A combined UV-BTF
      approach permitted faster biofilm formation and greater removal than BTF. DCM
      distribution and its photodegradation intermediates revealed that the lower
      filter of the UV-BTF contributed more to CO2 production; the upper filter
      assisted more with DCM removal. The UV-BTF kept secretion of extracellular
      polymeric substances at a normal level with an evenly distributed biomass.
      Pyrosequencing analysis showed that the dominant population in the combined
      biofilter was more diverse than that in BTF alone. Our data provide a foundation
      for understanding the effect of UV pretreatment on BTF performance and the
      microbial community. 

PMID- 24462988
TI  - Degradation of carbamazepine by Fe(II)-activated persulfate process.
AB  - Experimental studies were conducted to investigate the oxidative degradation of
      carbamazepine (CBZ), one of the most frequently detected pharmaceuticals in
      various waters, by Fe(II)-activated persulfate process. Results show that the
      Fe(2+)/S2O8(2-) process is very effective for the elimination of CBZ and
      characterized by a two-stage kinetics (a rapid initial decay followed by a
      retardation stage). CBZ degradation reaction was observed to be pH dependent and
      the optimum pH is 3.0 in the range of 2.00-7.87. The concentration of Fe(2+) and
      S2O8(2-) exhibited a noticeable influence on CBZ removal efficiency, where
      [S2O8(2-)] exerted more significant effects than that of [Fe(2+)]. The optimal
      molar ratio of CBZ, Fe(2+), and S2O8(2-) is found to be 1:5:40. The effect of
      various inorganic anions on CBZ removal was also evaluated under the optimal
      conditions. The anions NO3(-), SO4(2-) and H2PO4(-)caused a negative effect on
      the performance of this process, while Cl(-) interestingly accelerated CBZ
      degradation. The higher the Cl(-) concentration, the faster the CBZ decay rate.
      The intermediates were identified during CBZ degradation with and without the
      presence of Cl(-). The evolution of intermediates for these two scenarios was
      compared. The decay pathways of CBZ were proposed accordingly. 

PMID- 24462989
TI  - Adsorption of Procion Blue MX-R dye from aqueous solutions by lignin chemically
      modified with aluminium and manganese.
AB  - A macromolecule, CML, was obtained by purifying and carboxy-methylating the
      lignin generated from acid hydrolysis of sugarcane bagasse during bioethanol
      production from biomass. The CMLs complexed with Al(3+) (CML-Al) and Mn(2+) (CML
      Mn) were utilised for the removal of a textile dye, Procion Blue MX-R (PB), from
      aqueous solutions. CML-Al and CML-Mn were characterised using Fourier transform
      infrared spectroscopy (FTIR), scanning differential calorimetry (SDC), scanning
      electron microscopy (SEM) and pHPZC. The established optimum pH and contact time
      were 2.0 and 5h, respectively. The kinetic and equilibrium data fit into the
      general order kinetic model and Liu isotherm model, respectively. The CML-Al and
      CML-Mn have respective values of maximum adsorption capacities of 73.52 and
      55.16mgg(-1) at 298K. Four cycles of adsorption/desorption experiments were
      performed attaining regenerations of up to 98.33% (CML-Al) and 98.08% (CML-Mn)
      from dye-loaded adsorbents, using 50% acetone+50% of 0.05molL(-1) NaOH. The CML
      Al removed ca. 93.97% while CML-Mn removed ca. 75.91% of simulated dye house
      effluents. 

PMID- 24462990
TI  - Biliary cells to the rescue of Prometheus.

PMID- 24462991
TI  - Odd-looking gastric tumor.

PMID- 24462993
TI  - The role of chromatin and epigenetics in the polyphenisms of ant castes.
AB  - Ants and other social insects offer a natural experimental system to investigate
      the molecular bases of epigenetic processes that influence the whole organism.
      Epigenetics is defined as the inheritance of biological variation independent of
      changes in the DNA sequence. As such, epigenetic research focuses on the
      mechanisms by which multiple phenotypes arise from a single genome. In social
      insects, whole individuals belong to alternative phenotypic classes (known as
      castes) that vary in morphology, behavior, reproductive biology and longevity. It
      has been proposed that the same epigenetic pathways that maintain different cell
      identities in vertebrates might determine the different phenotypes observed in
      social insects. Here, I review the current progress on investigating the role of
      classic epigenetic signals, such as DNA methylation and histone posttranslational
      modification, in the relatively unexplored paradigm of ant polyphenism. 

PMID- 24462994
TI  - Nucleolar localization of SmMAK16 protein from Schistosoma mansoni is regulated
      by three distinct signals that function independent of pH or phosphorylation
      status.
AB  - SmMAK16 from the trematode Schistosoma mansoni is a protein that is known to
      localize in the nucleolus. Recent findings show that SmMAK16 is involved in 60S
      ribosomal subunit synthesis. Although the SmMAK16 protein contains putative
      nuclear localization signals (NLS), little is known about their precise function,
      redundancy or regulation. The goal of the current study was to identify and
      characterize the presence and functional regulation of the localization signals
      in SmMAK16. The SmMAK16 coding sequence and specific fragments were individually
      cloned in-frame into the pEGFP-C2 expression vector to encode Green Fluorescent
      Protein (GFP) fusion proteins. Constructs were individually transfected into COS
      7 cells and fluorescent microscopy used to determine the cellular location and
      thus the presence of signals regulating nuclear and nucleolar localization.
      SmMAK16 was found to contain two NLSs and one nucleolar localization signal
      (NoLS). One of the signals contains a sequence identical to an established
      nucleolar detention signal that reportedly functions only under acidic cellular
      conditions. The localization of the SmMAK16-GFP constructs was analyzed under
      acidic conditions; however, altering pH did not influence the localization of
      SmMAK16. It has been previously reported that casein kinase 2 (CK2) can
      phosphorylate SmMAK16 at serines adjacent to one of the NLSs. One of these CK2
      sites and the adjacent NLS are conserved with that of the SV40 Large T Antigen
      (LTA) and phosphorylation of this site in the SV40 LTA regulates the kinetics of
      the NLS. To discover if kinetic regulation also occurs in SmMAK16, mutant and
      wild type SmMAK16-GFP proteins were purified and injected into individual COS-7
      cells. No difference in the rate of transport was found between wt and mutant
      SmMAK16 proteins. Therefore, SmMAK16 localizes to the nucleolus using three
      separate signals, two NLSs and one NoLS, however, these signals appear to
      function independently of pH and phosphorylation by CK2. 

PMID- 24462995
TI  - Formal and informal home learning activities in relation to children's early
      numeracy and literacy skills: the development of a home numeracy model.
AB  - The purpose of this study was to propose and test a model of children's home
      numeracy experience based on Senechal and LeFevre's home literacy model (Child
      Development, 73 (2002) 445-460). Parents of 183 children starting kindergarten in
      the fall (median child age=58 months) completed an early home learning
      experiences questionnaire. Most of the children whose parents completed the
      questionnaire were recruited for numeracy and literacy testing 1 year later
      (along with 32 children from the inner city). Confirmatory factor analyses were
      used to reduce survey items, and hierarchical regression analyses were used to
      predict the relation among parents' attitudes, academic expectations for their
      children, reports of formal and informal numeracy, and literacy home practices on
      children's test scores. Parental reports of formal home numeracy practices (e.g.,
      practicing simple sums) predicted children's symbolic number system knowledge,
      whereas reports of informal exposure to games with numerical content (measured
      indirectly through parents' knowledge of children's games) predicted children's
      non-symbolic arithmetic, as did numeracy attitudes (e.g., parents' enjoyment of
      numeracy). The home literacy results replicated past findings; parental reports
      of formal literacy practices (e.g., helping their children to read words)
      predicted children's word reading, whereas reports of informal experiences (i.e.,
      frequency of shared reading measured indirectly through parents' storybook
      knowledge) predicted children's vocabulary. These findings support a multifaceted
      model of children's early numeracy environment, with different types of early
      home experiences (formal and informal) predicting different numeracy outcomes.

PMID- 24462996
TI  - Design, synthesis and pharmacological evaluation of novel pyrrolizine derivatives
      as potential anticancer agents.
AB  - A new series of novel pyrrolizine derivatives has been synthesized and
      biologically evaluated as potential anticancer agents. The starting compounds, 6
      amino-7-cyano-N-(3,5-disubstitutedphenyl)-2,3-dihydro-1H-pyrrolizine-5
      carboxamides 11a-b, were reacted with different acid chlorides, aldehydes and
      isocyanates to give the target compounds 12-14. Structural characterizations of
      the new compounds were performed using spectral and elemental analysis. All
      compounds were tested for their anticancer activity against human breast cancer
      and prostate cancer cell lines, MCF-7 and PC-3 respectively. With exception of
      compounds 11a and 13a, results revealed that all the tested compounds showed half
      maximal inhibitory concentration (IC50) values less than 40MUM. Compound 12b and
      the three urea derivatives 14b-d showed the most potent anticancer activity with
      IC50 values less than 2.73MUM. The anticancer activity of these compounds was
      mediated, at least in part, via the induction of apoptosis as indicated by its
      ability to activate caspase-3/7. In light of the high potency of our novel
      compounds in targeting both breast and prostate cancers, these compounds warrant
      continued preclinical development as potential anticancer agents. 

PMID- 24462997
TI  - Dynamics in the rhizosphere and iron-uptake gene expression in peanut induced by
      intercropping with maize: role in improving iron nutrition in peanut.
AB  - The intercropping of maize with peanuts is an effective cropping practice.
      Indeed, peanut/maize intercropping reportedly improves the iron nutrition of
      peanuts in calcareous soils. The limited evidence available suggests that the
      improved Fe nutrition in intercropping is largely attributable to a rhizosphere
      effect of maize. In this study, the effects of peanut/maize intercropping on the
      Fe nutritional status of peanut associated with the dynamics of the rhizosphere
      processes and Fe uptake gene expression induced by the interaction of the two
      species at various growth days were investigated. The results suggest that an
      interspecific rhizosphere effect improves Fe nutrition in peanut, as shown by
      changes in the rhizosphere available Fe concentration, pH, and Olsen-P
      concentration, based on time-course changes in peanut-maize interaction. The
      increase in available Fe in the rhizosphere of peanut ranged from 0.2 to 2.64 mg
      kg(-1). The transition from the vegetative to reproductive stage was a key
      turning point in the time-course of changes in the rhizosphere processes in
      intercropping. There was more consistently positive effect of intercropping on
      peanut Fe nutrition after 53 days. Moreover, the expression of AhFRO1 and AhYSL1
      was expressed at significantly higher level in intercropped peanuts compared to
      monocropped peanut at the vegetative stage, indicating a role for these genes in
      Fe improvement in intercropped peanuts. We conclude that the enhanced time-course
      changes in the rhizosphere processes and iron uptake gene expression with a
      consistent positive interspecific effect appear to be one of the mechanisms
      underlying the improved Fe nutrition in intercropped peanut plants.

PMID- 24462998
TI  - Upregulation of TFAM and mitochondria copy number in human lymphoblastoid cells.
AB  - Mitochondria are central to several physiological and pathological conditions in
      humans. In the present study, we performed copy number analysis of nuclear
      encoded mitochondrial genes, in peripheral blood mononuclear cells (PBMCs) and
      its representative lymphoblastoid cells (LCLs). We have observed hyper diploid
      copies of mitochondrial transcription factor A (TFAM) gene in the LCLs along with
      increased mtDNA copy number, mitochondrial mass, intracellular ROS and
      mitochondrial membrane potential, suggesting elevated mitochondrial biogenesis in
      LCLs. Gene expression analysis confirmed TFAM over-expression in LCLs when
      compared to PBMC. Based on our observation, we suggest that increased copy number
      of TFAM gene upregulates its expression, increases mtDNA copy numbers and
      protects it from oxidative stress induced damage in the transformed LCLs. 

PMID- 24462999
TI  - Laboratory investigation of oil-suspended particulate matter aggregation under
      different mixing conditions.
AB  - Oil-suspended particulate matter aggregation (OSA) has been recognized by the oil
      spill remediation community to effectively enhance the cleansing of spilled oil
      in the marine environment. While studies have investigated the application of
      mineral fines as an effective method to facilitate oil dispersion, decision
      makers still lack information on the role of mixing energy in OSA formation and
      its significance to oil dispersion in real spills. This work studied the effect
      of level and duration of mixing energy on OSA formation using the standard
      reference material 1,941 b and Arabian light crude oil. The results showed that
      dispersed small oil droplets increased with an increase of both the level and
      duration of mixing energy to form multi-droplet OSAs. The sizes of the dispersed
      droplets varied between 5 and 10 MUm under different conditions studied. The
      maximum oil trapping efficiency increased from 23% to 33%, the oil to sediment
      ratio increased from 0.30 to 0.43 g oil/g sediment, and the required shaking time
      decreased from 2.3 to 1.1h as the shaking rate increased from 2.0 to 2.3 Hz.
      Based on the size measurement results, a breakage effect on the formed OSAs and
      sediment flocs was confirmed under high mixing energy level.

PMID- 24463001
TI  - Release of cadmium, copper and lead from urban soils of Copenhagen.
AB  - We studied the bonding and release kinetics of Cd, Cu and Pb from different soils
      in the older metropolitan area of Copenhagen. Total Cd, Cu and Pb concentrations
      were elevated 5-27 times in the urban soils compared to an agricultural reference
      soil, with Cd and Pb in mainly mobilisable pools and Cu in strongly bound pools.
      The soils were subjected to accelerated leaching studies in Ca(NO3)2 or HNO3
      solutions resulting in release up to 78, 18 and 15% of total Cd, Cu and Pb soil
      concentrations over a period of 15 weeks. The relative initial Cd and Pb release
      rates increased 10 fold when pH decreased 2 and 3 units, respectively, while
      increases in Cu release rates were only seen at pH below 4. The total leachable
      Cu and Pb pools were higher in urban soils compared the agricultural reference
      soil but not for Cd. 

PMID- 24463002
TI  - Functional cortical connectivity analysis of mental fatigue unmasks hemispheric
      asymmetry and changes in small-world networks.
AB  - Changes in functional connectivity across mental states can provide richer
      information about human cognition than simpler univariate approaches. Here, we
      applied a graph theoretical approach to analyze such changes in the lower alpha
      (8-10 Hz) band of EEG data from 26 subjects undergoing a mentally-demanding test
      of sustained attention: the Psychomotor Vigilance Test. Behavior and connectivity
      maps were compared between the first and last 5 min of the task. Reaction times
      were significantly slower in the final minutes of the task, showing a clear time
      on-task effect. A significant increase was observed in weighted characteristic
      path length, a measure of the efficiency of information transfer within the
      cortical network. This increase was correlated with reaction time change.
      Functional connectivity patterns were also estimated on the cortical surface via
      source localization of cortical activities in 26 predefined regions of interest.
      Increased characteristic path length was revealed, providing further support for
      the presence of a reshaped global topology in cortical connectivity networks
      under fatigue state. Additional analysis showed an asymmetrical pattern of
      connectivity (right>left) in fronto-parietal regions associated with sustained
      attention, supporting the right-lateralization of this function. Interestingly,
      in the fatigue state, significance decreases were observed in left, but not right
      fronto-parietal connectivity. Our results indicate that functional network
      organization can change over relatively short time scales with mental fatigue,
      and that decreased connectivity has a meaningful relationship with individual
      difference in behavior and performance.

PMID- 24463000
TI  - The role of D2-autoreceptors in regulating dopamine neuron activity and
      transmission.
AB  - Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine
      neurons and control the synthesis, release and uptake of dopamine. These Gi/o
      coupled inhibitory receptors play a major part in shaping dopamine transmission.
      Found at both somatodendritic and axonal sites, autoreceptors regulate the firing
      patterns of dopamine neurons and control the timing and amount of dopamine
      released from their terminals in target regions. Alterations in the expression
      and activity of autoreceptors are thought to contribute to Parkinson's disease as
      well as schizophrenia, drug addiction and attention-deficit hyperactivity
      disorder (ADHD), which emphasizes the importance of D2-autoreceptors in
      regulating the dopamine system. This review will summarize the cellular actions
      of dopamine autoreceptors and discuss recent advances that have furthered our
      understanding of the mechanisms by which D2-receptors control dopamine
      transmission. 

PMID- 24463003
TI  - Can metabolic impairments in experimental diabetes be cured with poly(amido)amine
      (PAMAM) G4 dendrimers? In the search for minimizing of the adverse effects of
      PAMAM administration.
AB  - Poly(amido)amine (PAMAM) G4 dendrimers, given intraperitoneally to diabetic rats,
      have been reported to scavenge excessive blood glucose and minimize the effects
      of hyperglycaemia, however, at the cost of reduced survival. This paper is the
      first to compare the effectiveness of three different routes of PAMAM G4
      administration with regard to minimizing the adverse effects of hyperglycaemia in
      rats. Hence, the aim of the study is to identify the most effective and the least
      harmful method of dendrimer administration. Control and streptozotocin-diabetic
      Sprague-Dawley rats were exposed to PAMAM G4 (0.5 MUmol/kg b.w.) for 60 days,
      administered intraperitoneally, intragastrically or subcutaneously.
      Intraperitoneal and subcutaneous administration of PAMAM G4 was found to be most
      effective in suppressing the long-term markers of hyperglycaemia, while the
      intragastric route appeared the least effective. Otherwise, the greatest
      incidence of adverse effects was associated with intraperitoneal and the lowest
      with subcutaneous delivery. Harmful effects of intragastrical administration were
      much lower compared to intraperitoneal route, but at the cost of reduced
      hypoglycaemizing potential. Otherwise, subcutaneous injection represents the best
      compromise of moderate PAMAM dendrimer toxicity and effective reduction in the
      markers of long-term severe hyperglycaemia in chronic experimental diabetes.

PMID- 24463005
TI  - Emulsion-based colloidal nanosystems for oral delivery of doxorubicin: improved
      intestinal paracellular absorption and alleviated cardiotoxicity.
AB  - We have previously reported that the limited intestinal absorption via the
      paracellular pathway may be the primary cause of the low oral bioavailability of
      doxorubicin (DOX). In this study, we have formulated medium chain glycerides
      based colloidal nanosystems to enhance the intestinal paracellular absorption of
      DOX and reduce its cardiotoxicity. The DOX formulations prepared by the
      construction of pseudo-ternary phase diagram were characterized in terms of their
      droplet size distribution, viscosity, drug loading, and drug release. Further
      evaluation was conducted by an in vitro Caco-2 transport study as well as in
      situ/in vivo intestinal absorption, bioavailability and toxicity studies.
      Compared with DOX solution, these formulations enhanced the absorptive transport
      of DOX across Caco-2 cell monolayers at least partly due to the paracellular
      enhancing effects of their lipidic components. Moreover, the in situ intestinal
      absorption and in vivo oral bioavailability of DOX in rats were markedly
      enhanced. In addition, no discernible damage was observed in the rat jejunum
      after oral administration of these DOX formulations while the cardiac toxicity
      was significantly reduced when compared with intravenous DOX solution. Taken
      together, the medium chain glycerides-based colloidal nanosystems prepared in
      this study represent a potentially effective oral delivery system for DOX. 

PMID- 24463004
TI  - Starch-coated magnetic liposomes as an inhalable carrier for accumulation of
      fasudil in the pulmonary vasculature.
AB  - In this study, we tested the feasibility of magnetic liposomes as a carrier for
      pulmonary preferential accumulation of fasudil, an investigational drug for the
      treatment of pulmonary arterial hypertension (PAH). To develop an optimal
      inhalable formulation, various magnetic liposomes were prepared and characterized
      for physicochemical properties, storage stability and in vitro release profiles.
      Select formulations were evaluated for uptake by pulmonary arterial smooth muscle
      cells (PASMCs) - target cells - using fluorescence microscopy and HPLC. The
      efficacy of the magnetic liposomes in reducing hyperplasia was tested in 5-HT
      induced proliferated PASMCs. The drug absorption profiles upon intratracheal
      administration were monitored in healthy rats. Optimized spherical liposomes -
      with mean size of 170 nm, zeta potential of -35mV and entrapment efficiency of
      85% - exhibited an 80% cumulative drug release over 120 h. Fluorescence
      microscopic study revealed an enhanced uptake of liposomes by PASMCs under an
      applied magnetic field: the uptake was 3-fold greater compared with that observed
      in the absence of magnetic field. PASMC proliferation was reduced by 40% under
      the influence of the magnetic field. Optimized liposomes appeared to be safe when
      incubated with PASMCs and bronchial epithelial cells. Compared with plain
      fasudil, intratracheal magnetic liposomes containing fasudil extended the half
      life and area under the curve by 27- and 14-fold, respectively. Magnetic
      liposomes could be a viable delivery system for site-specific treatment of PAH.

PMID- 24463006
TI  - Phosphodiesterase types 3 and 4 regulate the phasic contraction of neonatal rat
      bladder smooth myocytes via distinct mechanisms.
AB  - Activation of the cyclic AMP (cAMP) pathway reduces bladder contractility.
      However, the role of phosphodiesterase (PDE) families in regulating this function
      is poorly understood. Here, we compared the contractile function of the cAMP
      hydrolyzing PDEs in neonatal rat bladder smooth myocytes. RT-PCR and Western
      blotting analysis revealed that several isoforms of PDE1-4 were expressed in
      neonatal rat bladder. While 8-methoxymethyl-3-isobutyl-1-methylxanthine (a PDE1
      inhibitor) and BAY-60-7550 (a PDE2 inhibitor) had no effect on the carbachol
      enhanced phasic contractions of bladder strips, cilostamide (Cil, a PDE3
      inhibitor) and Ro-20-1724 (Ro, a PDE4 inhibitor) significantly reduced these
      contractions. This inhibitory effect of Ro was blunted by the PKA inhibitor H-89,
      while the inhibitory effect of Cil was strongly attenuated by the PKG inhibitor
      KT 5823. Application of Ro in single bladder smooth myocytes resulted in an
      increase in Ca(2+) spark frequency but a decrease both in Ca(2+) transients and
      in sarcoplasmic reticulum (SR) Ca(2+) content. In contrast, Cil had no effect on
      these events. Furthermore, Ro-induced inhibition of the phasic contractions was
      significantly blocked by ryanodine and iberiotoxin. Taken together, PDE3 and PDE4
      are the main PDE isoforms in maintaining the phasic contractions of bladder
      smooth myocytes, with PDE4 being functionally more active than PDE3. However,
      their roles are mediated through different mechanisms. 

PMID- 24463007
TI  - AKT3 regulates ErbB2, ErbB3 and estrogen receptor alpha expression and
      contributes to endocrine therapy resistance of ErbB2(+) breast tumor cells from
      Balb-neuT mice.
AB  - ErbB2(+) breast cancer is an aggressive breast cancer subtype generally
      associated with lower estrogen receptor alpha (ERalpha) expression and more
      aggressive tumor behavior compared to ERalpha(+)/ErbB2(-) breast cancer. The
      ErbB2(+) phenotype is associated with resistance to endocrine therapy, e.g. the
      selective estrogen receptor modulator Tamoxifen. However, the mechanisms
      underlying endocrine resistance are not fully understood. Here, we investigated
      the impact of AKT signaling and distinct functional roles of AKT isoforms in
      ErbB2(+) breast cancer from Balb-neuT mice. AKT isoform specific in vitro kinase
      assays revealed that AKT3 is activated in Balb-neuT breast tumors in comparison
      to normal murine breast tissue. Knock-down of AKT3, but not of AKT1 or AKT2, led
      to reduced expression and tyrosine-phosphorylation of ErbB2 and ErbB3 in Balb
      neuT-derived mammary tumor cells. In contrast, expression of ERalpha was strongly
      up-regulated and phosphorylation of the AKT substrate Foxo3a which regulates
      ERalpha transcription was decreased in AKT3 knockdown cells. These data suggest
      that ERalpha expression is down regulated via AKT3/Foxo3a signaling in ErbB2(+)
      breast cancer cells. Furthermore, up-regulation of ERalpha after depletion of
      AKT3 resulted in a significant increase in Tamoxifen responsiveness of Balb-neuT
      derived mammary tumor cells. In addition, Tamoxifen resistant human breast cancer
      cell lines showed increased AKT3 expression and activity in comparison to
      Tamoxifen responsive MCF-7 cells. Finally, by AKT isoform specific in vitro
      kinase assays of human breast cancer samples, AKT3 activity was detected in
      ErbB2(+) and triple negative tumors but not in ERalpha(+) breast cancer. Our data
      indicate that AKT3 regulates the expression of ErbB2, ErbB3 and ERalpha and
      demonstrate that down-regulation of activated AKT3 can sensitize ErbB2(+) breast
      cancer cells for treatment with Tamoxifen. Therefore, AKT3 targeting might be a
      new promising strategy for therapy of ErbB2(+)/ERalpha(-) breast cancer and might
      further increase the responsiveness to an endocrine therapy approach. 

PMID- 24463009
TI  - Familial strife on the seashore: aggression increases with relatedness in the sea
      anemone Actinia equina.
AB  - Pairwise contests occur when two individuals compete directly over ownership of
      an indivisible resource. Contests vary in the degree of escalation, some
      encounters being settled through non-injurious behaviour while others are only
      resolved after dangerous fighting. Here, we investigate the role of relatedness,
      assessed using AFLP analysis, on the occurrence of stinging during staged
      contests in the beadlet sea anemone Actinia equina. Contrary to our expectations,
      we found that the chance of stinging, and hence the chance of inflicting damage,
      increased with the degree of relatedness between the two opponents. This result
      may be explained by the negative relationship between asymmetry in fighting
      ability and escalation level predicted by theory. We suggest that in order to
      fully understand how relatedness influences aggression, predictions from kin
      selection theory should be incorporated with those from contest theory. 

PMID- 24463008
TI  - Canonical Wnt signaling skews TGF-beta signaling in chondrocytes towards
      signaling via ALK1 and Smad 1/5/8.
AB  - BACKGROUND: Both Wnt signaling and TGF-beta signaling have been implicated in the
      regulation of the phenotype of many cell types including chondrocytes, the only
      cell type present in the articular cartilage. A changed chondrocyte phenotype,
      resulting in chondrocyte hypertrophy, is one of the main hallmarks of
      osteoarthritis. TGF-beta signaling via activin-like kinase (ALK)5, resulting in
      Smad 2/3 phosphorylation, inhibits chondrocyte hypertrophy. In contrast, TGF-beta
      signaling via ALK1, leading to Smad 1/5/8 phosphorylation, has been shown to
      induce chondrocyte hypertrophy. In this study, we investigated the capability of
      Wnt3a and WISP1, a protein downstream in canonical Wnt signaling, to skew TGF
      beta signaling in chondrocytes from the protective Smad 2/3 towards the Smad
      1/5/8 pathway. RESULTS: Stimulation with Wnt3a, either alone or in combination
      with its downstream protein WISP1, decreased TGF-beta-induced C-terminal
      phosphorylation of Smad 2/3. In addition, both Wnt3a and WISP1 increased Smad
      1/5/8 phosphorylation at the C-terminal domain in both murine and human
      chondrocytes. DKK-1, a selective inhibitor of canonical Wnt signaling, abolished
      these effects. TGF-beta signaling via Smad 2/3, measured by the functional CAGA12
      Luc reporter construct activity, was decreased by stimulation with Wnt3a in
      accordance with the decrease in Smad 2/3 phosphorylation found on Western blot.
      Furthermore, in vivo overexpression of the canonical Wnt8a decreased Smad 2/3
      phosphorylation and increased Smad 1/5/8 phosphorylation. CONCLUSIONS: Our data
      show that canonical Wnt signaling is able to skew TGF-beta signaling towards
      dominant signaling via the ALK1/Smad 1/5/8 pathway, which reportedly leads to
      chondrocyte hypertrophy. In this way canonical Wnts and WISP1, which we found to
      be increased during experimental osteoarthritis, may contribute to osteoarthritis
      pathology.

PMID- 24463010
TI  - Bronchial responsiveness in an elastase-induced mouse model of emphysema.
AB  - Bronchial responsiveness during methacholine (MCh) challenge was analysed in an
      elastase-induced mouse model of emphysema to explore the magnitude of the
      response in this model. Swiss mice were intratracheally instilled with saline or
      elastase (0.3 or 0.6 U). Twenty days afterward, mechanical ventilation data were
      collected from the closed and opened thorax of baseline and MCh (vehicle, 50 and
      100 mg/mL) challenged mice. The lungs were prepared for morphometric analysis. In
      the 0.6 U group, airway resistance (Raw) and tissue elastance (H) were decreased,
      and hysteresivity (eta) was increased (closed thorax). MCh increased Raw, G and H
      in all groups, but this increase was attenuated in the elastase-induced emphysema
      groups, the largest attenuation was observed in the 0.6 U (closed thorax
      condition). Elastase increased hyperinflation of the alveoli, alveolar collapse
      and the Lm and reduced the normal area. MCh reduced respiratory mechanics in
      elastase-induced emphysema, and this reduction was modulated by the collapsed
      and/or hyperinflated areas, which increased the heterogeneity of the lungs.

PMID- 24463011
TI  - Characterization of mycobacterial UDP-N-acetylglucosamine enolpyruvyle
      transferase (MurA).
AB  - The mycobacterial peptidoglycan has structure and biosynthetic pathways to
      similar those of other bacteria. UDP-N-acetylglucosamine enolpyruvyle transferase
      (MurA) catalyzes the first reaction in the biosynthesis of peptidoglycan. The
      MurA enzyme has been identified from various bacterial species, but the in-depth
      biochemical properties of mycobacterial MurA have not been characterized. In this
      study, both Mycobacterium tuberculosis MurA protein and Mycobacterium smegmatis
      MurA protein were overexpressed in Escherichia coli and purified by affinity
      chromatography. MurA activity was detected by HPLC. A colorimetric assay of MurA
      activity was also developed and the kinetic properties of Mtb MurA and Msm MurA
      were determined using this colorimetric assay. A conditional murA gene knockout
      strain was constructed by DNA homologous recombination. The disruption of murA in
      the genome of M. smegmatis led to loss of viability at a non-permissive
      temperature. Drastic morphological and structural alterations in the M. smegmatis
      murA knockout strain were observed by scanning electron microscopy and
      transmission electron microscopy. These results demonstrated that murA was an
      essential gene for growth of M. smegmatis. Therefore, MurA is a potential target
      for developing new anti-tuberculosis drugs. 

PMID- 24463012
TI  - Bacterial endosymbionts in field-collected samples of Trialeurodes sp. nr.
      abutiloneus (Hemiptera: Aleyrodidae).
AB  - Facultative bacterial endosymbionts are common, influential associates of
      arthropods, yet their movement among host species has not been well documented.
      Plant-mediated transmission of Rickettsia has been shown for the whitefly Bemisia
      tabaci. Bemisia tabaci in USA cotton fields harbors the secondary symbionts
      Rickettsia and Hamiltonella, and co-occurs with Trialeurodes sp. nr. abutiloneus
      whiteflies. To determine whether symbionts may be shared, the microbial diversity
      of these whiteflies on cotton across the USA was analyzed. Trialeurodes sp. nr.
      abutiloneus bore Portiera, Pseudomonas, Serratia, Arsenophonus and Wolbachia. No
      Rickettsia or Hamiltonella were detected. These results provide no evidence for
      horizontal transmission of symbionts between these whitefly genera. 

PMID- 24463013
TI  - The soil carbon/nitrogen ratio and moisture affect microbial community structures
      in alkaline permafrost-affected soils with different vegetation types on the
      Tibetan plateau.
AB  - In the Tibetan permafrost region, vegetation types and soil properties have been
      affected by permafrost degradation, but little is known about the corresponding
      patterns of their soil microbial communities. Thus, we analyzed the effects of
      vegetation types and their covariant soil properties on bacterial and fungal
      community structure and membership and bacterial community-level physiological
      patterns. Pyrosequencing and Biolog EcoPlates were used to analyze 19 permafrost
      affected soil samples from four principal vegetation types: swamp meadow (SM),
      meadow (M), steppe (S) and desert steppe (DS). Proteobacteria, Acidobacteria,
      Bacteroidetes and Actinobacteria dominated bacterial communities and the main
      fungal phyla were Ascomycota, Basidiomycota and Mucoromycotina. The ratios of
      Proteobacteria/Acidobacteria decreased in the order: SM>M>S>DS, whereas the
      Ascomycota/Basidiomycota ratios increased. The distributions of carbon and
      nitrogen cycling bacterial genera detected were related to soil properties. The
      bacterial communities in SM/M soils degraded amines/amino acids very rapidly,
      while polymers were degraded rapidly by S/DS communities. UniFrac analysis of
      bacterial communities detected differences among vegetation types. The fungal
      UniFrac community patterns of SM differed from the others. Redundancy analysis
      showed that the carbon/nitrogen ratio had the main effect on bacteria community
      structures and their diversity in alkaline soil, whereas soil moisture was mainly
      responsible for structuring fungal communities. Thus, microbial communities and
      their functioning are probably affected by soil environmental change in response
      to permafrost degradation. 

PMID- 24463014
TI  - A continuous and direct assay to monitor leucine-rich repeat kinase 2 activity.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a multi-domain enzyme displaying
      activities of GTP hydrolase and protein threonine/serine kinase in separate
      domains. Mutations in both catalytic domains have been linked to the onset of
      Parkinson's disease, which triggered high interest in this enzyme as a potential
      target for drug development, particularly focusing on inhibition of the kinase
      activity. However, available activity assays are discontinuous, involving either
      radioactivity detection or coupling with antibodies. Here we describe a
      continuous and direct assay for LRRK2 kinase activity, combining a reported
      peptide sequence optimized for LRRK2 binding and an established strategy for
      fluorescence emission on magnesium ion chelation by phosphorylated peptides
      carrying an artificial amino acid. The assay was employed to evaluate apparent
      steady-state parameters for the wild type and two mutant forms of LRRK2
      associated with Parkinson's disease as well as to probe the effects of GTP, GDP,
      and autophosphorylation on the kinase activity of the enzyme. Staurosporine was
      evaluated as an inhibitor of the wild-type enzyme. It is expected that this assay
      will aid in mechanistic investigations of LRRK2. 

PMID- 24463015
TI  - Bioorthogonal click chemistry to assay mu-opioid receptor palmitoylation using 15
      hexadecynoic acid and immunoprecipitation.
AB  - We have developed a modification of bioorthogonal click chemistry to assay the
      palmitoylation of cellular proteins. This assay uses 15-hexadecynoic acid (15
      HDYA) as a chemical probe in combination with protein immunoprecipitation using
      magnetic beads in order to detect S-palmitoylation of proteins of interest. Here
      we demonstrate the utility of this approach for the mu-opioid receptor (MOR), a G
      protein-coupled receptor (GPCR) responsible for mediating the analgesic and
      addictive properties of most clinically relevant opioid agonist drugs. This
      technique provides a rapid, non-isotopic, and efficient method to assay the
      palmitoylation status of a variety of cellular proteins, including most GPCRs. 

PMID- 24463016
TI  - Preparation of nitrophorin 7(Delta1-3) from Rhodnius prolixus without start
      methionine using recombinant expression in Escherichia coli.
AB  - The heterologous recombinant expression of proteins in Escherichia coli without
      start-methionine is a common problem. The nitrophorin 7 heme properties and
      function strongly depend on the accurate N-terminal amino acid sequence. Leading
      protein expression into the periplasm by fusion with the leader peptide pelB
      yields functional protein; however, the folded protein sticks to the cell debris.
      Therefore, the periplasmic fraction was dissolved in guanidinium chloride and
      folded by a drop-in method. Separation from impurities including residual pelB
      nitrophorin 7 required establishing an unconventional chromatographic technique
      using calcium-loaded Chelating Sepharose as cation exchanger and elution by a
      linear CaCl2 gradient. 

PMID- 24463017
TI  - Evaluation of non-immunoaffinity methods for isolation of cellular prion protein
      from bovine brain.
AB  - Transmissible spongiform encephalopathies (TSEs) are progressive
      neurodegenerative diseases that affect the central nervous system of many
      animals, including humans. Research suggests that TSEs are caused by conversion
      of the cellular prion protein (PrP(C)), which is encoded in many tissues,
      especially brain, to the pathological form (PrP(Sc)). This conversion affects
      PrP(Sc) structure, conferring different biochemical properties, such as the
      increased resistance to proteinase K, that have been widely used for its
      purification. By contrast, PrP(C) is less resistant and its isolation is more
      challenging. Here, we propose a purification strategy to efficiently recover
      PrP(C) from healthy bovine brain using conventional non-immunoaffinity methods.
      The applicability of extraction using detergents, size exclusion chromatography,
      diafiltration with molecular weight cutoff (MWCO) filters, and immobilized metal
      affinity chromatography (IMAC) using Western blot (WB) analysis to detect the
      presence of PrP(C) is discussed in detail. 

PMID- 24463018
TI  - A particular set of small non-coding RNAs is bound to the distinctive Argonaute
      protein of Trypanosoma cruzi: insights from RNA-interference deficient organisms.
AB  - The study of small RNAs and Argonaute proteins in eukaryotes that are deficient
      in functional RNA interference could provide insights into novel functions of
      small RNAs. In this study we describe small non-coding RNAs bound to a
      distinctive Argonaute protein of Trypanosoma cruzi, TcPIWI-tryp. Co
      immunoprecipitation of TcPIWI-tryp followed by deep sequencing of isolated RNA
      identified abundant small RNAs derived from rRNAs and tRNAs. The small RNA
      repertoire differed from that of the canonical Argonaute in organisms with
      functional RNA interference, which could indicate novel biological functions for
      TcPIWI-tryp in T. cruzi and other members of the trypanosomatid clade.

PMID- 24463019
TI  - Genetic variations in insulin-like growth factor binding protein acid labile
      subunit gene associated with growth traits in beef cattle (Bos taurus) in China.
AB  - The insulin-like growth factor binding protein acid labile subunit (IGFALS) gene
      encodes a serum protein that binds to IGFs and regulates growth, development, and
      other physiological processes. We have found that sequencing of the IGFALS gene
      in Chinese Qinchuan beef cattle (n=300) revealed four SNP loci in exon two of the
      gene (g1219: T>C, g1893: T>C, g2612: G>A, and g2696: A>G). The SNP g2696: A>G
      resulted in a change from asparagine to aspartic acid (p. N574D) in the leucine
      rich repeat region in the carboxyl-terminal domain of IGFALS. Four SNPs were in
      low linkage disequilibrium, and 12 different haplotypes were identified in the
      population. Association analysis suggested that SNP g1219: T>C had a significant
      association with hip width (P<0.05) and SNP g2696: A>G displayed a significant
      association with stature (P<0.05). The results from our investigation indicated
      that polymorphisms in the IGFALS gene were associated with growth traits of
      bovine, and may serve as a genetic marker for selection of beef cattle for growth
      traits, including stature.

PMID- 24463020
TI  - Linkage disequilibrium and haplotype distribution of the bovine LHX4 gene in
      relation to growth.
AB  - LIM homeobox transcription factor 4 (LHX4) is a LIM homeodomain transcription
      factor involved in pituitary gland and nervous system development. The aim of
      this study was to examine the association of the LHX4 polymorphisms with growth
      traits in beef cattle breed. A total of 7 single nucleotide polymorphyisms (SNPs)
      have been identified in the coding region and noncoding region of the bovine LHX4
      by sequencing pooled DNA samples (Pool-Seq) and PCR-single strand conformation
      polymorphism (PCR-SSCP) methods. The linkage disequilibrium was assessed in 871
      individuals representing four main cattle breeds from China. The SNPs 2-5 and 7-8
      were found to be in complete linkage disequilibrium, respectively. The result of
      haplotype analysis of 13 SNPs showed that 31 haplotypes were found in four
      Chinese cattle breeds, and 20 genotypes were only found in Nanyang cattle. The
      statistical analyses indicated that the SNP1-5, and 6 are associated with the
      body weight at 18, and 6 months of age in Nanyang cattle population (P<0.05), but
      no significant associations between their twenty combined genotypes. Our results
      provide evidence that some polymorphisms in LHX4 are associated with growth
      traits at certain ages, and may be used as candidates for marker-assisted
      selection and management in cattle.

PMID- 24463021
TI  - Unsupervised multiple endmember spectral mixture analysis-based detection of
      opium poppy fields from an EO-1 Hyperion image in Helmand, Afghanistan.
AB  - Since 1992, Afghanistan has gradually become the primary illicit opium producer
      in the entire world. To efficiently eradicate the opium poppy, it is crucial for
      the United Nations Office on Drugs and Crime (UNODC) and Ministry of Counter
      Narcotics of Afghanistan to monitor opium poppy cultivation timely. In situ
      detection of opium fields, however, is often expensive, time-consuming and
      dangerous in Afghanistan. To overcome the constraints of inaccessibility of opium
      fields, high-resolution (<=1 m) images, like pan-sharpened IKONOS, have been
      applied in previous studies. Unfortunately, these high-resolution images are
      expensive when monitoring a large area. In contrast, EO-1 Hyperion imagery, the
      only source of spaceborne hyperspectral data, has a coarse resolution (30 m), but
      it is free of charge. Moreover, Hyperion's large number of channels may increase
      the detection capability of subpixel size targets. Until now, however, little
      research has been found that identified opium fields from spaceborne or aerial
      hyperspectral images. Therefore, this study attempts to detect opium fields from
      a Hyperion image covering a study area in Southwest Afghanistan in a situation
      where training samples were not available. A proposed methodology based on
      unsupervised endmember-selection and multiple-endmember spectral mixture analysis
      can detect opium fields directly from the Hyperion image. The number of poppy
      pixels was overestimated by 12%.

PMID- 24463022
TI  - Predicting the impacts of bioenergy production on farmland birds.
AB  - Meeting European renewable energy production targets is expected to cause
      significant changes in land use patterns. With an EU target of obtaining 20% of
      energy consumption from renewable sources by 2020, national and local policy
      makers need guidance on the impact of potential delivery strategies on ecosystem
      goods and services to ensure the targets are met in a sustainable manner. Within
      agroecosystems, models are available to explore consequences of such policy
      decisions for food, fuel and fibre production but few can describe the effect on
      biodiversity. This paper describes the integration and application of a farmland
      bird population model within a geographical information system (GIS) to explore
      the consequences of land use changes arising from different strategies to meet
      renewable energy production targets. Within a 16,000 ha arable dominated case
      study area in England, the population growth rates of 19 farmland bird species
      were predicted under baseline land cover, a scenario maximising wheat production
      for bioethanol, and a scenario focused on mix of bioenergy sources. Both
      scenarios delivered renewable energy production targets for the region (>12 kWh
      per person per day) but, despite differences in resultant landscape composition,
      the response of the farmland bird community as a whole to each scenario was small
      and broadly similar. However, this similarity in overall response masked
      significant intra- and inter-specific variations across the study area and
      between scenarios suggesting contrasting mechanisms of impact and highlighting
      the need for context dependent, species-level assessment of land use change
      impacts. This framework provides one of the first systematic attempts to
      spatially model the effect of policy driven land use change on the population
      dynamics of a suite of farmland birds. The GIS framework also facilitates its
      integration with other ecosystem service models to explore wider synergies and
      trade offs arising from national or local policy interventions.

PMID- 24463023
TI  - Nanoscale zero-valent iron for the removal of Zn2+, Zn(II)-EDTA and Zn(II)
      citrate from aqueous solutions.
AB  - The parameters which influence the removal of different zinc (Zn) species:
      Zn(2+), Zn(II)-EDTA and Zn(II)-citrate from aqueous solutions by nanoparticles of
      zero-valent iron (nZVI) were investigated at environmental relevant pH values.
      Untreated, surface modified and silica-fume supported nZVI were applied at
      different iron loads and contact times to Zn solutions, which were buffered to pH
      5.3, 6.0 and 7.0. The results revealed that pH, the type of nZVI, the iron load,
      the contact time, and the Zn species all had a significant influence on the
      efficiency of removal. Zn(2+), Zn(II)-EDTA and Zn(II)-citrate were the most
      effectively removed from aqueous solutions by untreated nZVI. Zn(2+) removal was
      governed mainly by adsorption onto precipitated iron oxides. Complete removal of
      Zn(2+) and Zn(II)-citrate was obtained at all pH values investigated. The removal
      of strong Zn(II)-EDTA complex was successful only at acidic pH, which favored
      degradation of Zn(II)-EDTA. Consequently, the released Zn(2+) was completely
      removed from the solution by adsorption onto iron oxides.

PMID- 24463024
TI  - A glimpse of Escherichia coli O157:H7 survival in soils from eastern China.
AB  - Escherichia coli O157:H7 (E. coli O157:H7) is an important food-borne pathogen,
      which continues to be a major public health concern worldwide. It is known that
      E. coli O157:H7 survive in soil environment might result in the contamination of
      fresh produce or water source. To investigate how the soils and their properties
      affect E. coli O157:H7 survival, we studied E. coli O157:H7 survival dynamics in
      14 soils collected in eastern China from the warm-temperate zone to subtropical
      zone. Results showed that E. coli O157:H7 survival as a function of time can be
      well described by the Weibull model. The calculated td values (survival time to
      reach the detection limit, 100 colony forming units per gram oven-dried weight of
      soil) for the test soils were between 1.4 and 25.8 days. A significantly longer
      survival time (td) was observed in neutral or alkaline soils from north-eastern
      China (the warm-temperate zone) than that in acidic soils from south-eastern
      China (the subtropical zone). Distinct E. coli O157:H7 survival dynamics was
      related to soil properties. Stepwise multiple regression analysis revealed that
      the td values were significantly enhanced by soil microbial biomass carbon and
      total nitrogen, but were significantly reduced by amorphous Al2O3 and relative
      abundance of Chloroflexi. It should pay more attention to E. coli O157:H7 long
      survival in soils and its potential environmental contamination risk.

PMID- 24463025
TI  - Impacts of firecracker burning on aerosol chemical characteristics and human
      health risk levels during the Chinese New Year Celebration in Jinan, China.
AB  - Measurements for size distribution and chemical components (including water
      soluble ions, OC/EC and trace elements) of particles were taken in Jinan, China,
      during the 2008 Chinese New Year (CNY) to assess the impacts of firecracker
      burning on aerosol chemical characteristics and human health risk levels. On the
      eve of the CNY, the widespread burning of firecrackers had a clear contribution
      to the number concentration of small accumulation mode particles (100-500 nm) and
      PM2.5 mass concentration, with a maximum PM2.5 concentration of 464.02 MUg/m(3).
      The firecracker activities altered the number size distribution of particles, but
      had no influence on the mass size distribution of major water-soluble ions. The
      concentrations of aerosol and most ions peaked in the rush hour of firecracker
      burning, whereas the peaks of NO3(-) and NH4(+) presented on the day following
      the burning of firecrackers. K(+), SO4(2-) and Cl(-) composed approximately 62%
      of the PM2.5 mass, and they existed as KCl and K2SO4 during the firecracker
      period. However, during the non-firecracker period, organic matter (OM), SO4(2-),
      NO3(-) and NH4(+) were the major chemical components of the PM2.5, and major ions
      were primarily observed as (NH4)2SO4 and NH4NO3. Estimates of non-carcinogenic
      risk levels to human health showed that the elemental risk levels during the
      firecracker period were substantially higher than those observed during the non
      firecracker period. The total elemental risk levels in Jinan for the three groups
      (aged 2-6 years, 6-12 years and >=70 years) were higher than 2 during the
      firecracker period, indicating that increased pollutant levels emitted from the
      burning of firecrackers over short periods of time may cause non-carcinogenic
      human health risks.

PMID- 24463027
TI  - Increasing cadmium and zinc levels in wild common eiders breeding along Canada's
      remote northern coastline.
AB  - The common eider (Somateria mollissima) is an abundant sea duck breeding around
      the circumpolar Arctic, and is an important component of subsistence and sport
      harvest in some regions. We determined hepatic cadmium (Cd) and zinc (Zn)
      concentrations in the livers of breeding females sampled during three time
      periods including 1992/3, 2001/2 and 2008 at three sites spanning 53.7 degrees N
      75.8 degrees N in the eastern Canadian Arctic. At all sites, concentrations of
      both Cd and Zn increased ~300% over this time period. The reasons for this rapid
      increase in concentrations are unclear. 

PMID- 24463026
TI  - Concentrations and distribution of synthetic musks and siloxanes in sewage sludge
      of wastewater treatment plants in China.
AB  - In this study, we assessed the occurrence and distribution patterns of seven
      synthetic musks (SMs) and 17 siloxanes in anaerobic digested sludge samples
      collected at the dewatering process from 42 wastewater treatment plants (WWTPs)
      in China. SMs in sludge from different WWTPs exhibited similar composition
      profiles, and their total concentrations ranged from 47.3 ng/g to 68.2 MUg/g dry
      weight (dw). On average, galaxolide (HHCB, 63.8%) and tonalide (AHTN, 31.7%)
      accounted for 95.5% of ?SMs. The total concentrations of cyclic siloxanes ranged
      from <LOQ (limit of quantitation) to 36.1 MUg/g dw (mean: 1.98 MUg/g), while from
      <LOQ to 13.2 MUg/g dw (mean: 0.937 MUg/g) for linear siloxanes. On average,
      cyclic siloxanes accounted for 68% of the total siloxanes. High concentrations
      and detection frequencies of SMs and siloxanes in sewage sludge indicated that
      both of them were widely used in China. Among the sludge samples from 42 WWTPs,
      the concentrations of both ?SMs and ?siloxanes had considerable variations. We
      investigated the influence of potential factors (wastewater and sludge
      characteristics, the treatment capacity, serving population, and the treatment
      techniques of WWTPs) on the levels of target compounds in sludge, and found that
      SMs were significantly (p<0.05) correlated with the total organic carbon (TOC) of
      the sludge and the serving population of WWTP. There were also strong
      correlations (p<0.05) between the treatment capacity of WWTPs and cyclic
      siloxanes, as well as between the TOC of the sludge and linear siloxanes. In
      addition, the ecological risks of SMs and siloxanes in sewage sludge addressed to
      land application were assessed, which suggested that there was a low risk to the
      soil environment.

PMID- 24463028
TI  - AIRS retrieved CO2 and its association with climatic parameters over India during
      2004-2011.
AB  - Atmospheric Infrared Sounder (AIRS) retrieved mid-tropospheric Carbon Dioxide
      (CO2) have been used to study the variability and its association with the
      climatic parameters over India during 2004 to 2011. The study also aims in
      understanding transport of CO2 from surface to mid-troposphere over India. The
      annual cycle of mid-tropospheric CO2 shows gradual increase in concentration from
      January till the month of May at the rate ~0.6 ppm/month. It decreases
      continuously in summer monsoon (JJAS) at the same rate during which strong
      westerlies persists over the region. A slight increase is seen during winter
      monsoon (DJF). Being a greenhouse gas, annual cycle of CO2 show good resemblance
      with annual cycle of surface air temperature with correlation coefficient (CC) of
      +0.8. Annual cycle of vertical velocity indicate inverse pattern compared to
      annual cycle of CO2. High values of mid-tropospheric CO2 correspond to upward
      wind, while low values of mid-tropospheric CO2 correspond to downward wind. In
      addition to vertical motion, zonal winds are also contributing towards the
      transport of CO2 from surface to mid-troposphere. Vegetation as it absorbs CO2 at
      surface level, show inverse annual cycle to that of annual cycle of CO2 (CC
      0.64). Seasonal variation of rainfall-CO2 shows similarities with seasonal
      variation of NDVI-CO2. However, the use of long period data sets for CO2 at the
      surface and at the mid-troposphere will be an advantage to confirm these results.

PMID- 24463029
TI  - The interactive effects of multiple stressors on physiological stress responses
      and club cell investment in fathead minnows.
AB  - Anthropogenic activities have dramatically increased over the past decades, with
      the consequence that many organisms are simultaneously exposed to multiple
      stressors. Understanding how organisms respond to these stressors is a key focus
      for scientists from many disciplines. Here we investigated the interactive
      effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a
      common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to
      influence the density of epidermal club cells (ECCs), which are not only a key
      component of the innate immune system of fishes, but are also the source of
      chemical alarm cues that serve to warn other fishes of nearby predators. In
      contrast, Cd impairs the physiological stress response and ability of fish to
      respond to alarm cues. We used an integrative approach to examine physiological
      stress response as well as investment in ECCs. Fish exposed to UVR had higher
      levels of cortisol than non-exposed controls, but Cd reduced cortisol levels
      substantially for fish exposed to UVR. Fish exposed to UVR, either in the
      presence or absence of Cd, showed consistent decreases in ECC investment compared
      to non-exposed controls. Despite differences in ECC number, there was no
      difference in the potency of alarm cues prepared from the skin of UVR and Cd
      exposed or non-exposed fish indicating that UVR and Cd exposure combined may have
      little influence on chemically-mediated predator-prey interactions. 

PMID- 24463030
TI  - How soil organic matter composition controls hexachlorobenzene-soil-interactions:
      adsorption isotherms and quantum chemical modeling.
AB  - Hazardous persistent organic pollutants (POPs) interact in soil with the soil
      organic matter (SOM) but this interaction is insufficiently understood at the
      molecular level. We investigated the adsorption of hexachlorobenzene (HCB) on
      soil samples with systematically modified SOM. These samples included the
      original soil, the soil modified by adding a hot water extract (HWE) fraction
      (soil+3 HWE and soil+6 HWE), and the pyrolyzed soil. The SOM contents increased
      in the order pyrolyzed soil<original soil<soil+3 HWE<soil+6 HWE. For the latter
      three samples this order was also valid for the HCB adsorption. The pyrolyzed
      soil adsorbed more HCB than the other samples at low initial concentrations, but
      at higher concentrations the HCB adsorption became weaker than in the samples
      with HWE addition. This adsorption combined with the differences in the chemical
      composition between the soil samples suggested that alkylated aromatic, phenol,
      and lignin monomer compounds contributed most to the HCB adsorption. To obtain a
      molecular level understanding, a test set has been developed on the basis of
      elemental analysis which comprises 32 representative soil constituents. The
      calculated binding energy for HCB with each representative system shows that HCB
      binds to SOM stronger than to soil minerals. For SOM, HCB binds to alkylated
      aromatic, phenols, lignin monomers, and hydrophobic aliphatic compounds stronger
      than to polar aliphatic compounds confirming the above adsorption isotherms.
      Moreover, quantitative structure-activity relationship (QSAR) of the binding
      energy with independent physical properties of the test set systems for the first
      time indicated that the polarizability, the partial charge on the carbon atoms,
      and the molar volume are the most important properties controlling HCB-SOM
      interactions. 

PMID- 24463031
TI  - Distribution of phthalate acid esters in lakes of Beijing and its relationship
      with anthropogenic activities.
AB  - The distribution of 15 phthalate acid esters (PAEs) in water, sediment and
      suspended particle samples from representative lakes of Beijing was investigated
      and its relationship with anthropogenic activities was also assessed. The sample
      preparation and analysis methods for PAEs, using solid-phase extraction or
      microwave assisted extraction coupled with gas chromatography-mass spectrometry,
      were developed to achieve the satisfactory detection limits and recoveries. The
      analysis results indicated occurrences of most target PAEs were widespread in the
      researched lakes with the total PAE concentrations ranged from 0.386 to 3.184
      MUg/L in water, from 52.6 to 8216.4 ng/g dry weight in sediments and from 138.7
      to 2052.4 MUg/g dry weight in suspended particles. Di-(2-ethylhexyl) phthalate
      and di-butyl phthalate were the predominant PAEs, frequently being detected in
      all matrices, followed by di-iso-butyl phthalate and butyl benzyl phthalate. It
      was also found that anthropogenic activities were associated with the spatial
      distribution of phthalates in sediments considering its relationship with
      population distribution characteristics of Beijing.

PMID- 24463032
TI  - Indoor air quality in a bar/restaurant before and after the smoking ban in
      Athens, Greece.
AB  - In this study we compared indoor air pollutant concentrations in a bar/restaurant
      in Greece before and after the enactment of a smoking ban legislation of 2008.
      This was done to investigate whether the separation of the venue into smoking and
      non-smoking areas will have an impact on workers and customers from secondhand
      smoke (SHS) exposure (null hypothesis). The study was completed within an 8-month
      period beginning in March 2010 and ending on November 2010. We compared the
      average of the measured PM0.1 concentrations in the smoking zones between the pre
      ban and post-ban periods. Overall reduction in the number of particles was 18%
      between pre-ban and post-ban periods. The mean of the 36 total CO2 measurements
      for the pre- and the post-ban period was 611ppm. We calculated the ventilation
      rates per occupant (Vo in l/s/occ) and found it to be higher in the post-ban
      period (19.4l/s/occ), thus complying with the ASHARAE standard for Vo of
      15l/s/occ at maximum occupancy, than in the pre-ban period (10.7l/s/occ). The
      mean of the 36 total CO measurements for the pre-ban period was 2 ppm. CO
      measurements in the post-ban period were less than the detection limit of 1 ppm.
      Emissions of nitrogen dioxide and formaldehyde weren't detected in any of the
      zones. It was observed there was about 50% distribution of pollutants from the
      smoking zones to the smoke-free zones. The smoking ban effect on the occupancy
      levels was initially reduced by 16%, but based on other similar studies this
      transition period will be followed by an increase in the occupancy. Passive
      smoking and associated risks were significantly reduced but not totally
      eliminated, indicating the need for stronger enforcement or complete partition
      between smoking and non-smoking areas.

PMID- 24463033
TI  - Pharmacological characterization and chemical fractionation of a liposterolic
      extract of saw palmetto (Serenoa repens): effects on rat prostate contractility.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Saw palmetto (Serenoa repens) was first used
      medicinally by native American Indians to treat urological disorders. Nowadays,
      saw palmetto extracts are widely used in Europe and North America to treat the
      urinary symptoms associated with benign prostatic hyperplasia even though its
      mechanisms of action are poorly understood. This study aimed to characterize the
      bioactive constituents of a lipid extract of saw palmetto that are able to affect
      contractility of the rat prostate gland. The mechanism of action will also be
      investigated. MATERIALS AND METHODS: A commercially available lipid extract of
      saw palmetto was subjected to fractionation using normal phase column
      chromatography. Composition of fractions was assessed by proton nuclear magnetic
      resonance spectroscopy ((1)H NMR) and mass spectrometry (MS). Contractile
      activities of these fractions were evaluated pharmacologically using isolated
      preparations of rat prostate gland and compared to the activity of the crude
      extract. RESULTS: Saw palmetto extract inhibited contractions of the rat prostate
      gland which were consistent with smooth muscle relaxant activity. Only the ethyl
      acetate fraction resulting from chromatography inhibited contractions of isolated
      rat prostates similarly to the inhibition produced by the crude lipid extract.
      Comparison with authentic samples and analysis of NMR data revealed that this
      bioactivity was due to the fatty acid components present in the ethyl acetate
      fraction. Bioassay using various pharmacological tools identified multiple
      contractile mechanisms which were affected by the bioactive constituents.
      CONCLUSION: A fatty acid component of saw palmetto extract causes inhibition of
      prostatic smooth muscle contractions via a non-specific mechanism.

PMID- 24463034
TI  - Medicinal properties and conservation of Pelargonium sidoides DC.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pelargonium sidoides DC. (Geraniaceae), a popular
      medicinal plant used in traditional medicine in the treatment of gastrointestinal
      ailments has been transformed into a phytopharmaceutical (EPs((r)) 7360) for
      treating respiratory tract infections. The increasing international demand for
      Pelargonium sidoides has led to localised overexploitation of its wild
      populations in southern Africa. The aim of the review is to provide a synthesis
      of the current state of scientific knowledge on the phytochemical,
      pharmacological and toxicological properties of Pelargonium sidoides as well as
      the potential role of plant biotechnology in its conservation. The review
      highlights knowledge gaps in these research areas. MATERIALS AND METHODS: A
      comprehensive literature search involving mainly electronic and library sources
      of information were used to collate and synthesise published data. RESULTS:
      Experimental results from in vitro studies indicate that bioactive phytochemical
      constituents of Pelargonium sidoides may not possess a direct antimicrobial
      effect, but instead act by interfering with microbial binding to host cell
      receptors, inhibition of key enzymes and the production of antimicrobial effector
      molecules such as nitric oxide and interferons (IFNs) by the host cells.
      Furthermore, clinical evaluations in randomised, double-blind, placebo-controlled
      trials have demonstrated the beneficial effect of Pelargonium sidoides in the
      treatment of respiratory tract infections with few side effects. However, there
      is lack of adequate information on the safety evaluation of the plant. On the
      other hand, the increasing demand for Pelargonium sidoides has led to localised
      illegal harvesting of wild plants. CONCLUSIONS: Pharmacological data reported in
      literature suggest that Pelargonium sidoides shows a beneficial effect in the
      treatment of respiratory tract infections. However, more studies are required to
      elucidate the mode of action of the active constituents exhibited in the
      treatment of respiratory tract infections and other health conditions caused by
      microbial attack. Furthermore, the pharmacological usefulness of Pelargonium
      sidoides must take cognisance of the broader context involving the need for
      conservation-friendly approaches in its utilisation. In this regard, plant
      biotechnology applications can play a meaningful role in a holistic conservation
      strategy.

PMID- 24463036
TI  - Young adults' reactions to infant crying.
AB  - An infant's optimal development is determined to a great extent by the adequate
      and sensitive responses of the caregiver. The adequacy and sensitivity of a
      reaction to an infant in distress (i.e. crying) will partly depend on the causal
      attributions of the crying and on the individual's sympathy for the infant. Being
      female, prior caring experiences, and multiparity have shown to be linked to more
      sympathetic, tolerant and less hostile emotional responses to crying. However,
      little is known about other factors explaining inexperienced future caregivers'
      reactions to infant crying. The present paper's goal is to shed more light on the
      subject by looking at how personality factors, caregiving interest, sex,
      promptness of the reaction, and gender identity are related to emotional
      reactions and causal attributions to crying in a population of young adults
      without children. One hundred and ninety-one childless university students
      participated (126 females; ages 18-35 years). The participants completed
      questionnaires on personality, gender identity and caregiving interest, and
      listened to an audio sample of an infant crying, reporting their emotions and
      their causal attributions to the crying. The results showed that experiencing
      anger was associated with more child-blaming attributions to the crying, while
      quickness of response and feelings of sympathy predicted more child-oriented
      attributions. The latter was stronger in males. Explicit care interest decreased
      child-blaming causal attributions more for men than for the women. Interestingly,
      solely in the females' personality factors neuroticism and conscientiousness
      played a role in child blaming attributions together with anger. These findings
      suggest that the motives that young adults attribute to a crying infant depend in
      males on the emotions triggered by the crying, responsiveness and care interest.
      While in females, emotions, responsiveness and personality affect the causal
      attribution to the crying. Future research is needed in order to determine
      whether these attributions are also linked to young adults' actual behaviour
      towards a crying infant. 

PMID- 24463035
TI  - Targeting alpha-synuclein with a microRNA-embedded silencing vector in the rat
      substantia nigra: positive and negative effects.
AB  - BACKGROUND: Alpha-synuclein (SNCA) downregulation shows therapeutic potential for
      synucleinopathies, including Parkinson's disease (PD). Previously we showed that
      human (h)SNCA gene silencing using a short hairpin (sh)RNA in rat substantia
      nigra (SN) protects against a hSNCA-induced forelimb deficit, but not dopamine
      (DA) neuron loss. Furthermore, the shRNA increases cell death in vitro, but the
      same target sequence embedded in a microRNA30 transcript (mir30-hSNCA) does not.
      OBJECTIVE: Examine hSNCA gene silencing using mir30-hSNCA in vivo. METHODS: Rats
      were stereotaxically injected into one SN with adeno-associated virus serotype
      2/8 (AAV)-hSNCA, AAV-hSNCA plus AAV-mir30-SNCA or AAV-hSNCA plus a control non
      silencing mir30-embedded siRNA and DA neuron markers and associated behavior were
      examined. RESULTS: AAV2/8-mediated SN hSNCA expression induces a forelimb deficit
      and tyrosine hydroxylase-immunoreactive (TH-IR) neuron loss. hSNCA gene silencing
      using mir30-hSNCA protects against this forelimb deficit at 2 m and ameliorates
      TH-IR neuron loss. Striatal (ST) TH-IR fiber density and DA markers, assessed by
      western blot, are unaffected by AAV-hSNCA alone. Co-expression of either
      silencing vector reduces ST TH-IR fibers, panTH in SN and Ser40 phosphorylated TH
      in SN and ST, but does not affect vesicular monoamine transporter-2. However,
      hSNCA gene silencing promotes partial TH-IR fiber recovery by 2 m. Co-expression
      of either silencing vector also induces SN inflammation, although some recovery
      was observed by 2 m in hSNCA-silenced SN. CONCLUSION: hSNCA gene silencing with
      AAV-mir30-hSNCA has positive effects on forelimb behavior and SN DA neurons,
      which are compromised by inflammation and reduced TH expression, suggesting that
      AAV2/8-mir30-hSNCA-mediated gene silencing, although promising in vitro, is not a
      candidate for therapeutic translation for PD.

PMID- 24463037
TI  - Motherhood in adolescent mothers: maternal attachment, mother-infant styles of
      interaction and emotion regulation at three months.
AB  - Early motherhood is considered a risk factor for an adequate relationship between
      mother and infant and for the subsequent development of the infant. The principal
      aim of the study is to analyze micro-analytically the effect of motherhood in
      adolescence on the quality of mother-infant interaction and emotion regulation at
      three months, considering at the same time the effect of maternal attachment on
      these variables. Participants were 30 adolescent mother-infant dyads compared to
      30 adult mother-infant dyads. At infant 3 months, mother-infant interaction was
      video-recorded and coded with a modified version of the Infant Caregiver
      Engagement Phases and the Adult Attachment Interview was administered to the
      mother. Analysis showed that adolescent mothers (vs. adult mothers) spent more
      time in negative engagement and their infants spent less time in positive
      engagement and more time in negative engagement. Adolescent mothers are also less
      involved in play with their infants than adult mothers. Adolescent mother-infant
      dyads (vs. adult mother-infant dyads) showed a greater duration of negative
      matches and spent less time in positive matches. Insecure adolescent mother
      infant dyads (vs. insecure adult mother-infant dyads) demonstrated less
      involvement in play with objects and spent less time in positive matches. To sum
      up adolescent mother-infant dyads adopt styles of emotion regulation and
      interaction with objects which are less adequate than those of dyads with adult
      mothers. Insecure maternal attachment in dyads with adolescent mothers (vs. adult
      mother infant dyads) is more influential as risk factor. 

PMID- 24463038
TI  - The homogeneity effect on figure/ground perception in infancy.
AB  - We examined whether the homogeneity of the two profiles of Rubin's goblet affects
      figure/ground perception in infants. We modified the two profiles of Rubin's
      goblet in order to compare figure/ground perception under four test patterns: (1)
      two profiles painted with horizontal lines (horizontal-line condition), (2) two
      profiles painted middle gray (uni-color condition), (3) one profile painted light
      gray and the other dark gray (two-color condition), and (4) a goblet painted with
      concentric circles (concentric-circles condition). In the horizontal-line
      condition the homogeneity of the profile was strengthened, and in the two-color
      condition the homogeneity of the profile was weakened compared to the uni-color
      condition, which was an original Rubin's goblet. In the concentric-circles
      condition the homogeneity of the reversed areas of the horizontal-line were
      strengthened. After infants were familiarized with each Rubin's goblet, the
      infants were tested on their discrimination between the two profiles and the
      goblet in the post-familiarization test. In horizontal-line condition, uni-color
      condition and concentric-circles condition infants showed a novelty preference
      for the two profiles in the post-familiarization test. On the other hand, in the
      two-color condition no preference was observed in the post-familiarization test.
      This means that infants perceived the goblet as figure and the two profiles as
      ground in the horizontal-line condition, the uni-color condition and the
      concentric-circles condition. We found that infants could not perceive the goblet
      area as figure when the homogeneity of the two profiles was weakened. It can be
      said that figure/ground perception in infancy is not affected by strengthened
      homogeneity, but is affected by weakened homogeneity. 

PMID- 24463039
TI  - Infant shy temperament predicts preschoolers Theory of Mind.
AB  - The aim of this longitudinal study was to investigate the relation between infant
      temperament at 18 months and early Theory of Mind (ToM) abilities at 3 years of
      age. Temperament was assessed with the Early Childhood Behavior Questionnaire
      (ECBQ) and ToM by assessing children's understanding of divergent desires and
      beliefs, and of knowledge access. Our results are in line with a social-emotional
      reactivity perspective postulating more sophisticated ToM abilities for children
      with less reactive more observant temperament. Children with shy temperament at
      18 months and at 3 years were better in reasoning about others' mental states at
      age 3. Language, siblings and parental education had no effect on ToM. Findings
      indicate that temperament is related to ToM earlier in development than
      previously found, and that this relation is thus not unique to false-belief
      understanding. 

PMID- 24463040
TI  - Determination of clenbuterol from pork samples using surface molecularly
      imprinted polymers as the selective sorbents for microextraction in packed
      syringe.
AB  - In this study, a selective sample pretreatment procedure combing surface
      molecularly imprinted polymers and microextraction in packed syringe (SMIPs-MEPS)
      was developed for the analysis of clenbuterol (CLB) from pork samples. SMIPs for
      CLB were synthesized on silica gel particles through a sol-gel process. A series
      of characterization and adsorption experiments revealed that the SMIPs exhibited
      porous structures, good thermal stability, high adsorption capacity and a fast
      mass transfer rate. The obtained SMIPs were employed as selective sorbents of
      SMIPs-MEPS for extraction of CLB from pork samples. Several parameters affecting
      the extraction efficiency were investigated, including the pH of sample solution,
      number of draw-eject cycles, volume of sample, type and volume of washing
      solution, and the type and volume of elution solution. Under the optimized
      conditions, a simple and rapid method for the determination of CLB from pork
      samples was established by coupling with high performance liquid chromatography
      (HPLC). The whole pretreatment process was rapid and it can be accomplished with
      2min. The limit of quantitation and the limit of detection for CLB were 0.02 and
      0.009MUgkg(-1), respectively. The average recoveries of CLB at three spiked
      levels ranged from 86.5% to 91.2% with the relative standard deviations (RSD)
      <=6.3%. 

PMID- 24463041
TI  - A novel high resolution MS approach for the screening of 4-hydroxy-trans-2
      nonenal sequestering agents.
AB  - An in vitro high resolution mass spectrometry (MS) method was set-up to test the
      ability of compounds, mixtures and extracts to inhibit protein carbonylation
      induced by reactive carbonyl species (RCS). The method consists of incubating the
      protein target (ubiquitin) with 4-hydroxy-trans-2-nonenal (HNE) in the presence
      and absence of the tested compound. After 24h of incubation, the reaction is
      stopped and the protein is analyzed by high-resolution MS. The extent of protein
      carbonylation is determined by measuring the area of the +11 multicharged peak of
      the HNE adduct in respect to the native form. The method was validated by
      measuring the effect of well-known RCS sequestering agents, namely
      aminoguanidine, pyridoxamine, hydralazine and carnosine, yielding a good
      reproducibility and the possibility to be automatable. All the compounds were
      found to dose-dependently inhibit the protein carbonylation with the following
      order of potency carnosine~hydralazine?aminoguanidine>pyridoxamine, as determined
      by calculating the UC50 values, that is the concentration required to inhibit
      ubiquitin carbonylation by 50%. A good correlation was found with the results
      obtained by measuring HNE consumption using an HPLC method optimized by a mobile
      phase set at pH 7.4, in order to stabilize the eluted adducts. The MS approach
      was then applied to test the effect of two selected natural extracts on protein
      carbonylation, i.e. green coffee bean extract and procyanidins from Vitis
      vinifera. In summary, this paper reports a validated and highly reproducible MS
      method to test the ability of pure compounds as well as natural extracts to act
      as protein carbonylation inhibitors. 

PMID- 24463042
TI  - Tryptophan 19 residue is the origin of bovine beta-lactoglobulin fluorescence.
AB  - beta-Lactoglobulin consists of a single polypeptide of 162 amino acid residues
      with 2 Trp residues, Trp 19 present in a hydrophobic pocket and Trp 61 present at
      the surface of the protein near the pocket. This study aimed to characterize the
      respective contribution of the two Trp residues to the overall fluorescence of
      the protein. We added for that calcofluor white, an extrinsic fluorophore, which,
      at high concentration compared to that of the protein, quenches completely
      emission of hydrophobic Trp residue(s). The study was performed at different pHs
      by recording fluorescence steady state spectra and measuring fluorescence
      lifetimes of the Trp-residues using Single Time Photon Counting method. Our
      results indicate that addition of calcofluor white does not induce a red shift of
      the tryptophan(s) emission peak (332nm) but only a decrease in the fluorescence
      intensity. This means that Trp 61 residue does not contribute to the protein
      emission, tryptophan emission occurs from Trp 19 residue only. Also, excitation
      spectrum peak position (283nm) of beta-lactoglobulin is not modified upon
      calcofluor white binding. These results mean that structural rearrangements
      within beta-lactoglobulin are not occurring upon calcofluor white binding. Energy
      transfer between Trp 19 residue and calcofluor white occurs with 100% efficiency,
      i.e. the two fluorophores are very close one to each other (<5A). This energy
      transfer is not Forster type. Fluorescence intensity decay of Trp 19 residue
      occurs with three lifetimes, equal to 0.48, 1.49 and 4.29ns at pH 2 (monomeric
      state). Very close values were obtained at the different studied pHs (2-12) and
      where beta-lactoglobulin is at different quaternary structure or present in
      solution in a mixture of dimers and monomers. Our data are interpreted as the
      results of emission occurring from different substructures of the tryptophan,
      reached at the excited state. The populations of these substructures
      characterized by the pre-exponential parameters of the fluorescence lifetimes are
      dependent on the microenvironment of the fluorophore and on the local protein
      structure. 

PMID- 24463043
TI  - Optimization of SELEX: comparison of different methods for monitoring the
      progress of in vitro selection of aptamers.
AB  - Oligonucleotide aptamers are selected from libraries typically comprising up to
      10(15) different sequences by an iterative process of binding, separation,
      amplification and purification, called SELEX. During this process, the diversity
      of the oligonucleotide pool decreases until, presumably, only sequences with
      highest binding affinities towards chosen targets remain. This selection
      technique is time-consuming, labor-intensive and expensive. Though well posed in
      principles, the SELEX procedure is noise sensitive, due to amplification of
      unspecific-binding sequences, and it is not surprising that aptamer selection is
      often not successful in practice. In view of that, a follow-up of the progress of
      selection during its course with simple yet reliable methods is necessary. In
      this paper, we describe five independent assays to estimate the sequence
      complexity of SELEX pools including qualitative restriction fragment length
      polymorphism analysis, melting curve analysis, quantitative fluorescence
      intensity measurements of bound ssDNA, real time PCR quantification and pool
      dissociation constant analysis during the progress of aptamer selection against
      streptavidin. Properties and features of each method are discussed and compared.
      Pool dissociation constant analysis and sequencing serve as reference methods. 

PMID- 24463044
TI  - Comparison of Raman spectroscopy vs. high performance liquid chromatography for
      quality control of complex therapeutic objects: model of elastomeric portable
      pumps filled with a fluorouracil solution.
AB  - This study compares the performance of a reference method of HPLC to Raman
      spectroscopy (RS) for the analytical quality control (AQC) of complex therapeutic
      objects. We assessed a model consisting of a widely used anticancer drug, i.e., 5
      fluorouracil, which was compounded in a complex medical device, i.e., an
      elastomeric portable infusion pump. In view of the main objective, the two
      methods provided excellent results for the analytical validation key criteria,
      i.e., trueness, precision and accuracy, ranging from 7.5 to 50mg/mL and in either
      isotonic sodium or 5% dextrose. The Spearman and Kendall correlation tests (p
      value<1*10(-15)) and the statistical studies performed on the graphs confirm a
      strong correlation in the results between RS and the standard HPLC under the
      experimental conditions. The selection of a spectral interval between 700 and
      1400cm(-1) for both the characterization and quantification by RS was the result
      of a gradual process optimization, combining matrix and packaging responses. In
      this new application, we demonstrate at least eight benefits of RS: (a) operator
      safety, (b) elimination of disposables, (c) elimination of analysis waste, which
      contributes to the protection of the environment, (d) a fast analytical response
      of less than 2min, (e) the ability to identify the solubilizing phase, (f)
      reduction of the risk of errors because no intrusion or dilution are needed, (g)
      negligible maintenance costs and (h) a reduction in the budget dedicated to
      technician training. Overall, we indicate the potential of non-intrusive AQC
      performed by RS, especially when the analysis is not possible using the usual
      techniques, and the technique's high potential as a contributor to the safety of
      medication. 

PMID- 24463045
TI  - LC-MS method for the simultaneous determination of six glucocorticoids in
      pharmaceutical formulations and counterfeit cosmetic products.
AB  - A screening method based on liquid chromatography-electrospray mass spectrometry
      for the simultaneous determination of six corticosteroids (betamethasone 17
      valerate BM 17-V, beclomethasone BC, beclomethasone dipropionate BCDP,
      methylprednisolone MP, budesonide BD, flunisolide FN) was developed in order to
      control their illegal use in cosmetic and natural products. Indeed, despite
      corticosteroids are banned in cosmetics, counterfeit products might be present on
      the market, representing a health hazard. Therefore, effective analytical methods
      are required to rapidly screen over the counter products in health care shops for
      counterfeit corticosteroids. The analytical method involves the employment of a
      Waters Synergy C18 column (150mm*2.0mm I.D.) by using the following mobile phase:
      A (0.1% formic acid in acetonitrile), B (0.1% formic acid in water) in a linear
      gradient (from A-B 25:75, v/v to A-B 95:5, v/v in 30min) at the flow rate of
      0.3mL/min. The detection was performed with an ion trap (IT) mass spectrometer in
      positive polarity, total ion current (TIC) and tandem mass modalities for
      qualitative purpose; single ion monitoring (SIM) mode was used for quantitative
      analysis on the ESI generated most abundant ion for each steroid. The method was
      fully validated in terms of precision, detection and quantification limits,
      linearity, recovery, and it was applied to the identification and quantification
      of corticosteroids in pharmaceutical formulations and cosmetic products. The mean
      recovery of BM 17-V, BC, BCDP, MP, BD and FN were found to be 101.3, 101.5, 98.8,
      98.9, 98.1, 99.0%, respectively. Limits of quantitation (LOQ) were comprised in
      the range 29-95ng/mL. To the best of our knowledge, for the first time this mix
      of glucocorticoids were simultaneously determined in cosmetic products by using a
      fully validated method. BMV, in its two isomeric forms BM 17-V and BM 21-V, was
      found to be illegally present in one cream sample (A) with the total
      concentration level of 0.036% (w/w). 

PMID- 24463046
TI  - Direct analysis in real time mass spectrometry, a process analytical technology
      tool for real-time process monitoring in botanical drug manufacturing.
AB  - A promising process analytical technology (PAT) tool has been introduced for
      batch processes monitoring. Direct analysis in real time mass spectrometry (DART
      MS), a means of rapid fingerprint analysis, was applied to a percolation process
      with multi-constituent substances for an anti-cancer botanical preparation.
      Fifteen batches were carried out, including ten normal operations and five
      abnormal batches with artificial variations. The obtained multivariate data were
      analyzed by a multi-way partial least squares (MPLS) model. Control trajectories
      were derived from eight normal batches, and the qualification was tested by R(2)
      and Q(2). Accuracy and diagnosis capability of the batch model were then
      validated by the remaining batches. Assisted with high performance liquid
      chromatography (HPLC) determination, process faults were explained by
      corresponding variable contributions. Furthermore, a batch level model was
      developed to compare and assess the model performance. The present study has
      demonstrated that DART-MS is very promising in process monitoring in botanical
      manufacturing. Compared with general PAT tools, DART-MS offers a particular
      account on effective compositions and can be potentially used to improve batch
      quality and process consistency of samples in complex matrices. 

PMID- 24463047
TI  - Multi-responses extraction optimization based on response surface methodology
      combined with polarity switching HPLC-MS/MS for the simultaneous quantitation of
      11 compounds in Cortex Fraxini: application to four species of Cortex Fraxini and
      its 3 confusable species.
AB  - A novel polarity switching high performance liquid chromatography-electrospray
      ionization tandem mass spectrometry (HPLC-ESI-MS/MS) approach combining
      optimization of extraction condition by response surface methodology (RSM) was
      developed for the simultaneous quantitative analysis of 11 compounds in Cortex
      Fraxini, a commonly used traditional Chinese medicine. The ultrasonic extraction
      conditions of the 11 analytes including sample quantity, methanol concentration
      and extraction time were simultaneously optimized with a Box-Behnken design (BBD)
      and Derringer's desirability function. Multiple-reaction monitoring (MRM)
      scanning was employed for quantification with switching electrospray ion source
      polarity between positive and negative modes in a single run of 16min.
      Quantitative parameters of the proposed method with respect to limit of detection
      (LOD), limit of quantification (LOQ), linearity, precision, accuracy and
      stability were evaluated under optimum conditions, and the results indicated that
      the method was sensitive, specific and reliable. The developed method was
      successfully applied to determine the investigated compounds in four species of
      Cortex Fraxini and three kinds of its confusable species, and significant
      differences were found between the official and confusable species. 

PMID- 24463048
TI  - Aldehyde dehydrogenase enzyme ALDH3H1 from Arabidopsis thaliana: Identification
      of amino acid residues critical for cofactor specificity.
AB  - The cofactor-binding site of the NAD(+)-dependent Arabidopsis thaliana aldehyde
      dehydrogenase ALDH3H1 was analyzed to understand structural features determining
      cofactor-specificity. Homology modeling and mutant analysis elucidated important
      amino acid residues. Glu149 occupies a central position in the cofactor-binding
      cleft, and its carboxylate group coordinates the 2'- and 3'-hydroxyl groups of
      the adenosyl ribose ring of NAD(+) and repels the 2'-phosphate moiety of NADP(+).
      If Glu149 is mutated to Gln, Asp, Asn or Thr the binding of NAD(+) is altered and
      rendered the enzyme capable of using NADP(+). This change is attributed to a
      weaker steric hindrance and elimination of the electrostatic repulsion force of
      the 2'-phosphate of NADP(+). Simultaneous mutations of Glu149 and Ile200, which
      is situated opposite of the cofactor binding cleft, improved the enzyme
      efficiency with NADP(+). The double mutant ALDH3H1Glu149Thr/Ile200Val showed a
      good catalysis with NADP(+). Subsequently a triple mutation was generated by
      replacing Val178 by Arg in order to create a "closed" cofactor binding site. The
      cofactor specificity was shifted even further in favor of NADP(+), as the mutant
      ALDH3H1E149T/V178R/I200V uses NADP(+) with almost 7-fold higher catalytic
      efficiency compared to NAD(+). Our experiments suggest that residues occupying
      positions equivalent to 149, 178 and 200 constitute a group of amino acids in the
      ALDH3H1 protein determining cofactor affinity. 

PMID- 24463049
TI  - Long-term atorvastatin improves age-related endothelial dysfunction by
      ameliorating oxidative stress and normalizing eNOS/iNOS imbalance in rat aorta.
AB  - Vascular aging is characterized by vascular cell senescence, increased oxidative
      stress, and endothelial and inducible nitric oxide (NO) synthase (eNOS/iNOS)
      imbalance, which reduces NO bioavailability and causes endothelial dysfunction.
      We investigated whether long-term administration of atorvastatin affects
      endothelial dysfunction and the underlying mechanisms. Aortas from young (2
      months), middle-aged (12 months), and old (20 months) control rats that had
      received a routine diet and from old rats (20 months) that had received a diet
      mixed with atorvastatin (5 mg/kg/day) for 8 months were investigated. Senescent
      phenotype, vascular reactivity, superoxide dismutase (SOD), malonyldialdehyde
      (MDA), total NO, calcium-dependent and -independent NOS activity, and eNOS, iNOS,
      and sirtuin-1 (SIRT1) expression at the transcriptional and translational levels
      were assessed in rat aortas. Comparisons between young, middle, and old control
      rats showed that the senescent phenotype was enhanced in intima and media
      (p<0.01), and that MDA, calcium-independent NOS activity, and iNOS increased with
      age (p<0.01), whereas endothelium-dependent relaxation, SOD, NO, calcium
      dependent NOS activity, eNOS, the eNOS/iNOS ratio, and SIRT1 declined with age
      (p<0.01). Compared with old controls, long-term administration of atorvastatin to
      old rats inhibited the senescent phenotype (p<0.05), improved endothelium
      dependent relaxation (p<0.05 or 0.01), decreased MDA (p<0.01), increased SOD, NO,
      eNOS, and SIRT1 expression (p<0.01), and inhibited iNOS expression (not
      detectable) in aged rat aortas. The results indicate that the long-term
      administration of atorvastatin improves age-related endothelial dysfunction in
      aged rats via inhibition of the senescent phenotype, amelioration of oxidative
      stress, and normalization of eNOS/iNOS imbalance.

PMID- 24463050
TI  - Association of LRRTM3 polymorphisms with late-onset Alzheimer's disease in Han
      Chinese.
AB  - The leucine-rich repeat transmembrane 3 (LRRTM3) has been defined as a positional
      and functional candidate gene for Alzheimer's disease. Recently, four novel
      variants (rs16923760, rs1925608, rs1925609 and rs10997477) within LRRTM3 were
      reported to be associated with late-onset Alzheimer's disease (LOAD) in
      Caucasians. To evaluate the association of the LRRTM3 polymorphisms with LOAD in
      Asians, we performed a case-control study of 2287 unrelated subjects (1129 cases
      and 1158 age- and gender-matched controls) in Han Chinese. The rs10997477 T
      allele was significantly associated with a decreased risk of LOAD in APOE
      epsilon4 allele noncarriers (OR=0.750, PC<0.001). Besides, the rs16923760 C
      allele significantly increased the risk of LOAD in APOE epsilon4 allele carriers
      (OR=1.837, PC<0.001). The genotype distribution of rs1925609 polymorphism also
      significantly differed in APOE epsilon4 allele noncarriers (PC=0.008). Moreover,
      the association was further demonstrated in multivariate logistic regression
      analysis (rs10997477: Recessive model: OR=0.156, PC=0.004; Additive model:
      OR=0.731, PC<0.001; rs16923760: Dominant model: OR=1.944, PC=0.024; Additive
      model: OR=1.885, PC<0.001; Recessive model: OR=3.565, PC=0.010; rs1925609:
      Recessive model: OR=0.421, PC=0.024). As for rs1925608, we failed to detect any
      association with LOAD. This study firstly provides the independent evidence that
      the LRRTM3 polymorphisms may play a role in the pathogenesis of LOAD in a
      Northern Han Chinese population. However, additional independent replication
      groups are required to further validate this association. 

PMID- 24463051
TI  - Microbial inoculants and organic amendment improves plant establishment and soil
      rehabilitation under semiarid conditions.
AB  - The re-establishment of autochthonous shrub species is an essential strategy for
      recovering degraded soils under semiarid Mediterranean conditions. A field assay
      was carried out to determine the combined effects of the inoculation with native
      rhizobacteria (Bacillus megaterium, Enterobacter sp, Bacillus thuringiensis and
      Bacillus sp) and the addition of composted sugar beet (SB) residue on
      physicochemical soil properties and Lavandula dentata L. establishment. One year
      after planting, Bacillus sp. and B. megaterium + SB were the most effective
      treatments for increasing shoot dry biomass (by 5-fold with respect to control)
      and Enterobacter sp + SB was the most effective treatments for increasing dry
      root biomass. All the treatments evaluated significantly increased the foliar
      nutrient content (NPK) compared to control values (except B. thuringiensis + SB).
      The organic amendment had significantly increased available phosphorus content in
      rhizosphere soil by 29% respect to the control. Enterobacter sp combined with
      sugar beet residue improved total N content in soil (by 46% respect to the
      control) as well as microbiological and biochemical properties. The selection of
      the most efficient rhizobacteria strains and their combined effect with organic
      residue seems to be a critical point that drives the effectiveness of using these
      biotechnological tools for the revegetation and rehabilitation of degraded soils
      under semiarid conditions. 

PMID- 24463052
TI  - The time course of non-photochemical quenching in phycobilisomes of Synechocystis
      sp. PCC6803 as revealed by picosecond time-resolved fluorimetry.
AB  - As high-intensity solar radiation can lead to extensive damage of the
      photosynthetic apparatus, cyanobacteria have developed various protection
      mechanisms to reduce the effective excitation energy transfer (EET) from the
      antenna complexes to the reaction center. One of them is non-photochemical
      quenching (NPQ) of the phycobilisome (PB) fluorescence. In Synechocystis sp.
      PCC6803 this role is carried by the orange carotenoid protein (OCP), which reacts
      to high-intensity light by a series of conformational changes, enabling the
      binding of OCP to the PBs reducing the flow of energy into the photosystems. In
      this paper the mechanisms of energy migration in two mutant PB complexes of
      Synechocystis sp. were investigated and compared. The mutant CK is lacking
      phycocyanin in the PBs while the mutant DeltaPSI/PSII does not contain both
      photosystems. Fluorescence decay spectra with picosecond time resolution were
      registered using a single photon counting technique. The studies were performed
      in a wide range of temperatures - from 4 to 300 K. The time course of NPQ and
      fluorescence recovery in darkness was studied at room temperature using both
      steady-state and time-resolved fluorescence measurements. The OCP induced NPQ has
      been shown to be due to EET from PB cores to the red form of OCP under photon
      flux densities up to 1000 MUmolphotonsm-2s-1. The gradual changes of the energy
      transfer rate from allophycocyanin to OCP were observed during the irradiation of
      the sample with blue light and consequent adaptation to darkness. This fact was
      interpreted as the revelation of intermolecular interaction between OCP and PB
      binding site. At low temperatures a significantly enhanced EET from
      allophycocyanin to terminal emitters has been shown, due to the decreased back
      transfer from terminal emitter to APC. The activation of OCP not only leads to
      fluorescence quenching, but also affects the rate constants of energy transfer as
      shown by model based analysis of the decay associated spectra. The results
      indicate that the ability of OCP to quench the fluorescence is strongly
      temperature dependent. This article is part of a special issue entitled:
      photosynthesis research for sustainability: keys to produce clean energy.

PMID- 24463053
TI  - NADPH fluorescence in the cyanobacterium Synechocystis sp. PCC 6803: a versatile
      probe for in vivo measurements of rates, yields and pools.
AB  - We measured the kinetics of light-induced NADPH formation and subsequent dark
      consumption by monitoring in vivo its fluorescence in the cyanobacterium
      Synechocystis PCC 6803. Spectral data allowed the signal changes to be attributed
      to NAD(P)H and signal linearity vs the chlorophyll concentration was shown to be
      recoverable after appropriate correction. Parameters associated to reduction of
      NADP(+) to NADPH by ferredoxin-NADP(+)-oxidoreductase were determined: After
      single excitation of photosystem I, half of the signal rise is observed in 8ms;
      Evidence for a kinetic limitation which is attributed to an enzyme bottleneck is
      provided; After two closely separated saturating flashes eliciting two
      photosystem I turnovers in less than 2ms, more than 50% of the cytoplasmic
      photoreductants (reduced ferredoxin and photosystem I acceptors) are diverted
      from NADPH formation by competing processes. Signal quantitation in absolute
      NADPH concentrations was performed by adding exogenous NADPH to the cell
      suspensions and by estimating the enhancement factor of in vivo fluorescence
      (between 2 and 4). The size of the visible (light-dependent) NADP (NADP(+)+NADPH)
      pool was measured to be between 1.4 and 4 times the photosystem I concentration.
      A quantitative discrepancy is found between net oxygen evolution and NADPH
      consumption by the light-activated Calvin-Benson cycle. The present study shows
      that NADPH fluorescence is an efficient probe for studying in vivo the energetic
      metabolism of cyanobacteria which can be used for assessing multiple phenomena
      occurring over different time scales. 

PMID- 24463054
TI  - Thermodynamic and kinetic characterization of two methyl-accepting chemotaxis
      heme sensors from Geobacter sulfurreducens reveals the structural origin of their
      functional difference.
AB  - The periplasmic sensor domains GSU582 and GSU935 are part of methyl-accepting
      chemotaxis proteins of the bacterium Geobacter sulfurreducens containing one c
      type heme and a PAS-like fold. Their spectroscopic properties were shown
      previously to share similar spectral features. In both sensors, the heme group is
      in the high-spin form in the oxidized state and low-spin after reduction and
      binding of a methionine residue. Therefore, it was proposed that this redox
      linked ligand switch might be related to the signal transduction mechanism. We
      now report the thermodynamic and kinetic characterization of the sensors GSU582
      and GSU935 by visible spectroscopy and stopped-flow techniques, at several pH and
      ionic strength values. Despite their similar spectroscopic features, the midpoint
      reduction potentials and the rate constants for reduction by dithionite are
      considerably different in the two sensors. The reduction potentials of both
      sensors are negative and well framed within the typical anoxic subsurface
      environments in which Geobacter species predominate. The midpoint reduction
      potentials of sensor GSU935 are lower than those of GSU582 at all pH and ionic
      strength values and the same was observed for the reduction rate constants. The
      origin of the different functional properties of these closely related sensors is
      rationalized in the terms of the structures. The results suggest that the sensors
      are designed to function in different working potential ranges, allowing the
      bacteria to trigger an adequate cellular response in different anoxic subsurface
      environments. These findings provide an explanation for the co-existence of two
      similar methyl-accepting chemotaxis proteins in G. sulfurreducens. 

PMID- 24463055
TI  - Incompatibility of silver nanoparticles with lactate dehydrogenase leakage assay
      for cellular viability test is attributed to protein binding and reactive oxygen
      species generation.
AB  - A growing number of studies report that conventional cytotoxicity assays are
      incompatible with certain nanoparticles (NPs) due to artifacts caused by the
      distinctive characteristics of NPs. Lactate dehydrogenase (LDH) leakage assays
      have inadequately detected cytotoxicity of silver nanoparticles (AgNPs), leading
      to research into the underlying mechanism. When ECV304 endothelial-like umbilical
      cells were treated with citrate-capped AgNPs (cAgNPs) or bare AgNPs (bAgNPs), the
      plasma membrane was disrupted, but the LDH leakage assay failed to detect
      cytotoxicity, indicating interference with the assay by AgNPs. Both cAgNPs and
      bAgNPs inactivated LDH directly when treated to cell lysate as expected. AgNPs
      adsorbed LDH and thus LDH, together with AgNPs, was removed from assay reactants
      during sample preparation, with a resultant underestimation of LDH leakage from
      cells. cAgNPs, but not bAgNPs, generated reactive oxygen species (ROS), which
      were successfully scavenged by N-acetylcysteine or ascorbic acid. LDH inhibition
      by cAgNPs could be restored partially by simultaneous treatment with those
      antioxidants, suggesting the contribution of ROS to LDH inactivation.
      Additionally, the composition of the protein corona surrounding AgNPs was
      identified employing liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      analysis. In sum, the LDH leakage assay, a conventional cell viability test
      method, should be employed with caution when assessing cytotoxicity of AgNPs. 

PMID- 24463057
TI  - [New anticoagulants: a challenge for the medical training].

PMID- 24463056
TI  - Maternal single injection of N-methyl-N-nitrosourea to cause microcephaly in
      offspring induces transient aberration of hippocampal neurogenesis in mice.
AB  - N-Methyl-N-nitrosourea (MNU) is an alkylating agent having antiproliferative
      cytotoxity targeting the neural stem/progenitor cells to cause microcephaly by
      maternal exposure. This study investigated the effect of transient exposure to
      MNU on the process of hippocampal neurogenesis in later life using mice. Pregnant
      mice received a single injection of MNU at 0, 5 and 10 mg/kg body weight,
      intraperitoneally on gestational day 14, and their offspring were examined on
      postnatal day (PND) 21 and PND 77. On PND 21, offspring displayed microcephaly
      and hippocampal formation hypoplasia at 10 mg/kg, decrease of doublecortin
      (Dcx)(+) cells in the dentate subgranular zone from 5mg/kg, and decrease of
      TUNEL(+) apoptotic cells and increase of transcript expression of anti-apoptotic
      Bcl-2 at 10 mg/kg in the dentate gyrus. In the dentate hilus, numbers of
      reelin(+) or parvalbumin (Pvalb)(+) interneurons or neuron-specific nuclear
      protein(+) neurons increased at 10 mg/kg. Microcephaly and hippocampal formation
      hypoplasia continued through PND 77 at 10 mg/kg. Thus, apart from the massive
      cell killing at the migratory stream causing microcephaly, MNU may decrease
      Dcx(+) cells reflecting disruption of the differentiation process of late-stage
      neuronal progenitors and immature granule cells through defective molecular
      functions by gene mutations. Increase of reelin(+) and Pvalb(+) cells may reflect
      the disruption of neurogenesis and following neuronal migration. All of the
      granule cell lineage and interneuron changes disappeared at the adult stage on
      PND 77 suggesting that MNU mainly targets transient populations of highly
      proliferative progenitor cells but hardly affects their stem cells having self
      renewal ability.

PMID- 24463058
TI  - [General characteristics of the new oral anticoagulants].
AB  - Treatment with vitamin K antagonists are subject to a common iatrogenic mainly
      characterized by hemorrhagic stroke. Their narrow therapeutic range associated
      with variability largely explains this phenomenon. New oral anticoagulants (NOAC)
      are now available. dabigatran (Pradaxa(r)) is a direct and specific thrombin
      inhibitor. It is excreted mainly by the kidney and is the only which can be
      dialyzed. Rivaroxaban (Xarelto(r)) and apixaban (Eliquis(r)) are factor X
      activated direct inhibitors. They are highly bound to plasma proteins and are
      metabolized mainly by the liver, via CYP3A4. All NOAC are substrates of P
      glycoprotein (P-gp). Due to pharmacological changes, some populations at risk
      were identified: patients with hepatic impairment, renal impairment, elderly
      patients or low weight. Some pharmacokinetic or pharmacodynamic drug interactions
      alter the concentration and the expected impact of NOAC. The NOAC does not
      require biological monitoring. They interfere with the routine coagulation tests
      which should be interpreted with caution. Specific tests exist and can be used in
      case of emergencies. Currently, no antidote is available. The new oral
      anticoagulant look promising in the elderly. However, certain rules must be
      followed to reduce the risk of iatrogenic. 

PMID- 24463059
TI  - [Atrial fibrillation, comorbidities and new anticoagulants].
AB  - The atrial fibrillation (AF) is one of the most important cause of arythmia and
      cerebrovascular disease in clinical practice. Comorbidity is defined as the
      association of active chronical diseases and a target disease. METHOD: comparison
      between burden illness of the patients in interventional (n=4) and observational
      studies, form Medline database (n=4), was performed. RESULTS: the level of
      comorbidity tend to be higher in patients from interventional than large
      observational studies. DISCUSSION: in interventional studies, the level cerebro
      vascular risk was calculated to compare interventional and control groups. So
      contrary to what was expected the patients of the general population who can
      receive anticoagulants have a lesser burden of illness. A recent paper studying
      new anticoagulants in general population finds this difference again, and would
      indicate that the risk related to the use of new anticoagulants would not be
      upper to that observed in the princeps pivotal studies.

PMID- 24463060
TI  - [What is the current use of vitamin K antagonists in the elderly?].
AB  - With the recent marketing of the new oral anticoagulants (NOAC), the future of
      vitamin k antagonist (VKA) needs to be redefined. VKAs are drugs with a narrow
      therapeutic margin and a high iatrogenic risk that requires a close biological
      monitoring. Their efficacy has been proven for atrial fibrillation in numerous
      populations, especially in the elderly. Their side effects and interactions are
      well known. The measurement of the level of anticoagulation is possible and
      reliable using the INR (international normalized ratio) and an antidote is usable
      in case of emergency. The NOAC are at least as effective as VKA with slightly
      less side-effects especially cerebral hemorrhage, and they do not require
      biological monitoring. However, data on efficacy and side-effects of NOAC rely
      mainly on phase III clinical trials that did not particularly target
      polypathologic and frail populations. In these populations, we therefore have
      more "real life" information on VKA than NOAC. But studies on NOAC are currently
      conducted among these populations. A conservative approach would be to maintain
      VKA to older patients with stable INR. Lastly VKA are the only anticoagulant
      usable in case of severe renal failure and valvular fibrillation. 

PMID- 24463061
TI  - [Anticoagulant treatment in patients with atrial fibrillation, according to risk
      factors for stroke].
AB  - Atrial fibrillation (AF) is a common and serious condition in the elderly,
      concerning about 10% of people over 80. AF is a predictive factor for mortality
      in the elderly and a major risk factor for stroke. Approximately 15% of patients
      admitted for ischemic stroke have AF and the proportion increases with age,
      reaching about 40% in people over 80. Compared to patients with stroke unrelated
      to AF, patients with AF-associated stroke suffer from more severe strokes with an
      increased risk of remaining disabled after the event and have a higher risk of
      stroke recurrence. Although most ischemic strokes in AF patients are probably
      cardioembolic, due to migration of thrombi originating from the left atrial
      appendage, many elderly patients will be found to have other potential causes of
      stroke, such as extracranial or intracranial atherosclerotic stenosis, aortic
      arch atheroma, or small vessel disease. The absolute risk of stroke in patients
      with AF varies widely depending on associated risk factors, the most important
      being age over 75 and previous stroke or transient ischemic attack. Several
      scoring systems have been developed to help clinicians estimate the stroke risk
      on an individual basis and to guide the choice of the most appropriate preventive
      therapy. The management of AF in the elderly should involve a detailed evaluation
      of the patient's functional status and social situation. Specific precautions for
      treatment must be taken because of the co-morbidities and age-related changes in
      pharmacokinetics or pharmacodynamics. The benefits of VKAs have been largely
      shown in patients with AF and appear to be even more important among elderly
      people. Anticoagulants are recommended in patients with AF aged 75 years or above
      after assessing the bleeding risk. Novel oral anticoagulants (NOACs) are
      promising treatments, especially due to a lower risk of intracerebral
      haemorrhage. However, their prescriptions should take into account renal and
      cognitive functions. 

PMID- 24463062
TI  - [Novel oral anticoagulants and atrial fibrillation in the elderly].
AB  - Atrial fibrillation treatment relies on anticoagulation therapy that reduces the
      risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant
      drugs for more than 50 years, but they are difficult to manage especially in the
      elderly. In France, VKA are the main cause of iatrogenic hospitalizations with
      about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year.
      Pharmacologic properties of VKA, especially the narrow therapeutic margin explain
      the complexity of their management. Several studies have shown that patients
      treated with VKA were on average only 50% of the time with an INR in the
      therapeutic range. In other words, patients are, half of the time, either-under
      treated or over-treated. Within this framework, development of new oral
      anticoagulant drugs appeared necessary, in order to obtain drugs with larger
      therapeutic margin and a better risk/benefit profile than VKA. Three large
      randomized clinical trials including almost 50,000 patients with 20,000 subjects
      over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile
      of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction
      of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total
      mortality. Meanwhile, their renal elimination and the lack of control of the
      biological efficacy need to be taken into account for their prescription. Renal
      failure (estimated glomerular filtration rate according to Cockcroft formula < 30
      mL/min) contraindicates their use. Their half-life is shorter than that of VKA
      and the biological monitoring is not available, thus a good adherence to the
      treatment is important. Studies specifically conducted among geriatric older
      population with poly-pathologies and frail are therefore needed to evaluate
      tolerance of NOAC in real life conditions. 

PMID- 24463063
TI  - Using a biocultural approach to examine migration/globalization, diet quality,
      and energy balance.
AB  - The aim of this paper is to examine the role and impact that globalization and
      migration (e.g., intra-/intercontinental, urban/rural, and circular) have had on
      diet patterns, diet quality, and energy balance as reported on in the literature
      during the last 20 years. Published literature from the fields of anthropology,
      public health, nutrition, and other disciplines (e.g., economics) was collected
      and reviewed. In addition, case studies from the authors' own research are
      presented in order to elaborate on key points and dietary trends identified in
      the literature. While this review is not intended to be comprehensive, the
      findings suggest that the effects of migration and globalization on diet quality
      and energy balance are neither lineal nor direct, and that the role of social and
      physical environments, culture, social organization, and technology must be taken
      into account to better understand this relationship. Moreover, concepts such as
      acculturation and the nutrition transition do not necessarily explain or
      adequately describe all of the global processes that shape diet quality and
      energy balance. Theories from nutritional anthropology and critical bio-cultural
      medical anthropology are used to tease out some of these complex
      interrelationships.

PMID- 24463064
TI  - Association of PLA2G7 gene polymorphisms with ischemic stroke in northern Chinese
      Han population.
AB  - OBJECTIVE: Human lipoprotein-associated phospholipase A2 (Lp-PLA2), encoded by
      the PLA2G7 gene, plays an important role in the pathophysiology of inflammation.
      This study is aimed at evaluating the potential association of V279F and A379V in
      PLA2G7 gene with ischemic stroke where inflammatory process is involved. DESIGN
      AND METHODS: A total of 386 patients with ischemic stroke and 386 healthy
      controls were included in the study. The single nucleotide polymorphisms, V279F
      and A379V, were analyzed by the polymerase chain reaction-ligation detection
      reaction method. RESULTS: The frequencies of VV+AV genotype, AV genotype and V
      allele of A379V in the patients with ischemic stroke were significantly higher
      than those in the controls (P=0.02, P=0.03, P=0.02, respectively). These
      correlations still remained after adjusting for confounding risk factors of
      stroke. Furthermore, subgroup analysis showed that a significant association with
      A379V was found in large-artery atherosclerotic stroke subgroup. In addition, no
      significant association was observed between V279F and ischemic stroke.
      CONCLUSION: The study indicated that the A379V variant in PLA2G7 gene might
      contribute to ischemic stroke susceptibility in northern Chinese Han population.

PMID- 24463065
TI  - Increased expression of vascular endothelial growth factor and hypoxia inducible
      factor-1alpha in lung tissue of patients with chronic bronchitis.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) seems to be involved in the
      pathogenesis of chronic obstructive pulmonary disease (COPD), but its site
      specific expression in lung tissue and the relationship with hypoxia inducible
      factor-1 alpha (HIF-1alpha) expression in chronic bronchitis (CB) type COPD have
      not been studied. DESIGN AND METHODS: We evaluated the expression of VEGF and its
      receptors in various compartments of lung tissue in three groups: non-smokers
      with normal lung function (non-smokers, n=10), smokers without COPD (healthy
      smokers, n=10) and smokers with CB (CB, n=10), using immunohistochemical staining
      and Western blotting. The expression of HIF-1alpha was assessed by enzyme-linked
      immunosorbent assay. RESULTS: Compared with healthy smokers, VEGF expression in
      CB was significantly increased in bronchiolar epithelium, vascular endothelium
      and vascular smooth muscle (p<0.05). VEGF receptor (VEGFR)-2 expression in CB was
      also increased in bronchiolar smooth muscle, vascular endothelium and vascular
      smooth muscle compared with healthy smokers (p<0.05). The level of HIF-1alpha was
      increased in CB compared with healthy smokers and positively correlated with
      those of VEGF (r=0.64, p<0.05). CONCLUSION: VEGF and VEGFR-2 expressions were up
      regulated in CB and increased expression of VEGF was related with HIF-1alpha. HIF
      1alpha-regulated VEGF overexpression may be a characteristic of chronic
      bronchitis.

PMID- 24463067
TI  - Maternal restraint and external eating behaviour are associated with formula use
      or shorter breastfeeding duration.
AB  - Maternal eating behaviour (e.g. restraint, disinhibition) has been associated
      with maternal child-feeding style (e.g. pressure to eat, restricting intake,
      monitoring) for children over the age of two years. In particular, mothers high
      in restraint are significantly more likely to restrict and monitor their child's
      intake of food. Research has not however examined the impact of maternal eating
      behaviour upon earlier infant feeding. A controlling maternal child-feeding style
      has been linked with shorter breastfeeding duration and earlier introduction of
      solid foods but the relationship between infant milk feeding and maternal eating
      behaviour has not been explored despite links between maternal weight, body image
      and breastfeeding duration. The aim of the current study was to explore
      associations between maternal restraint, emotional and external eating and
      breastfeeding initiation and duration. Seven hundred and fifty-six mothers with
      an infant aged 6-12months completed a copy of the Dutch Eating Behaviour
      Questionnaire and reported breastfeeding duration and formula use up to six
      months postpartum. Mothers high in restraint and external eating were
      significantly more likely to formula feed from birth, to breastfeed for a shorter
      duration and to introduce formula milk sooner than those lower in these
      behaviours. Moreover these behaviours were associated with reporting greater
      control during milk feeding by feeding to a mother-led rather than baby-led
      routine. Maternal eating behaviour may therefore affect breastfeeding initiation
      and continuation and is an important element for discussion for those working to
      support new mothers. 

PMID- 24463066
TI  - Learning from nature - novel synthetic biology approaches for biomaterial design.
AB  - Many biomaterials constructed today are complex chemical structures that
      incorporate biologically active components derived from nature, but the field can
      still be said to be in its infancy. The need for materials that bring
      sophisticated properties of structure, dynamics and function to medical and non
      medical applications will only grow. Increasing appreciation of the functionality
      of biological systems has caused biomaterials researchers to consider nature for
      design inspiration, and many examples exist of the use of biomolecular motifs.
      Yet evolution, nature's only engine for the creation of new designs, has been
      largely ignored by the biomaterials community. Molecular evolution is an emerging
      tool that enables one to apply nature's engineering principles to non-natural
      situations using variation and selection. The purpose of this review is to
      highlight the most recent advances in the use of molecular evolution in synthetic
      biology applications for biomaterial engineering, and to discuss some of the
      areas in which this approach may be successfully applied in the future. 

PMID- 24463068
TI  - The effect of hydroxylated fatty acid-containing phospholipids in the remodeling
      of lipid membranes.
AB  - The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) is an antitumor drug that
      regulates membrane lipid composition and structure. An important effect of this
      drug is the restoration of sphingomyelin (SM) levels in cancer cell membranes,
      where the SM concentration is lower than in non-tumor cells. It is well known
      that free fatty acid concentration in cell membranes is lower than 5%, and that
      fatty acid excess is rapidly incorporated into phospholipids. In a recent work,
      we have considered the effect of free 2OHOA in model membranes in liquid ordered
      (Lo) and liquid disordered (Ld) phases, by using all-atom molecular dynamics.
      This study concerns membranes that are modified upon incorporation of 2OHOA into
      different phospholipids. 2OHOA-containing phospholipids have a permanent effect
      on lipid membranes, making a Ld membrane surface more compact and less hydrated,
      whereas the opposite effect is observed in Lo domains. Moreover, the hydroxyl
      group of fatty acid chains increases the propensity of Ld model membranes to form
      hexagonal or other non-lamellar structures. This article is part of a Special
      Issue entitled: Membrane Structure and Function: Relevance in the Cell's
      Physiology, Pathology and Therapy. 

PMID- 24463070
TI  - Investigating permeability related hurdles in oral delivery of 11-keto-beta
      boswellic acid.
AB  - 11-Keto-beta-boswellic acid (KBA) is an important and potent boswellic acids
      responsible for anti-inflammatory action of Boswellia extract. However, its
      pharmaceutical development has been severely limited by its poor oral
      bioavailability. The present work aims to investigate the permeability related
      hurdles in oral delivery of KBA. Gastrointestinal stability, gastrointestinal
      metabolism, adsorption-desorption kinetics and Caco-2 permeability studies have
      been carried out. KBA was found poorly permeable with Papp value of 2.85 +/- 0.14
      * 10(-6)cm/s. Higher absorptive transport indicated role of carrier mediated
      transport. Moreover, KBA transport across monolayer showed saturation kinetics at
      higher concentrations. KBA exposed to 1alpha,25-(OH)2 vitamin D3 treated cell
      monolayer showed the lowest Papp value of 2.01*10(-6) +/- 0.02 * 10(-6)cm/s
      indicating role of CYP3A4 mediated metabolism during KBA transport. Metabolic
      stability experiments in jejunum S9 fractions further confirmed this. KBA was
      found unstable in simulated gastrointestinal fluids and also got accumulated in
      the enterocytes. Sorption and desorption kinetic studies using Caco-2 cells
      further confirmed accumulation of KBA inside the enterocytes. KBA also showed pH
      dependent permeability with higher flux at gradient pH condition of pH 6.5 at
      apical and 7.4 at basolateral. Taken as whole, the major permeability related
      hurdles that hampered oral bioavailability of KBA included its gastrointestinal
      instability, CYP3A4 mediated intestinal metabolism, accumulation within the
      enterocytes and saturable kinetics. The present investigation may help in
      designing novel drug delivery system for KBA.

PMID- 24463071
TI  - Rational design of a series of novel amphipathic cell-penetrating peptides.
AB  - A series of novel, amphipathic cell-penetrating peptides was developed based on a
      combination of the model amphipathic peptide sequence and modifications based on
      the strategies developed for PepFect and NickFect peptides. The aim was to study
      the role of amphipathicity for peptide uptake and to investigate if the
      modifications developed for PepFect peptides could be used to improve the uptake
      of another class of cell-penetrating peptides. The peptides were synthesized by
      solid phase peptide synthesis and characterized by circular dichroism
      spectroscopy. Non-covalent peptide-plasmid complexes were formed by co-incubation
      of the peptides and plasmids in water solution. The complexes were characterized
      by dynamic light scattering and cellular uptake of the complexes was studied in a
      luciferase-based plasmid transfection assay. A quantitative structure-activity
      relationship (QSAR) model of cellular uptake was developed using descriptors
      including hydrogen bonding, peptide charge and positions of nitrogen atoms. The
      peptides were found to be non-toxic and could efficiently transfect cells with
      plasmid DNA. Cellular uptake data was correlated to QSAR predictions and the
      predicted biological effects obtained from the model correlated well with
      experimental data. The QSAR model could improve the understanding of structural
      requirements for cell penetration, or could potentially be used to predict more
      efficient cell-penetrating peptides. 

PMID- 24463069
TI  - High-quality 3D structures shine light on antibacterial, anti-biofilm and
      antiviral activities of human cathelicidin LL-37 and its fragments.
AB  - Host defense antimicrobial peptides are key components of human innate immunity
      that plays an indispensible role in human health. While there are multiple copies
      of cathelicidin genes in horses, cattle, pigs, and sheep, only one cathelicidin
      gene is found in humans. Interestingly, this single cathelicidin gene can be
      processed into different forms of antimicrobial peptides. LL-37, the most
      commonly studied form, is not only antimicrobial but also possesses other
      functional roles such as chemotaxis, apoptosis, wound healing, immune modulation,
      and cancer metastasis. This article reviews recent advances made in structural
      and biophysical studies of human LL-37 and its fragments, which serve as a basis
      to understand their antibacterial, anti-biofilm and antiviral activities. High
      quality structures were made possible by using improved 2D NMR methods for
      peptide fragments and 3D NMR spectroscopy for intact LL-37. The two hydrophobic
      domains in the long amphipathic helix (residues 2-31) of LL-37 separated by a
      hydrophilic residue serine 9 explain its cooperative binding to bacterial
      lipopolysaccharides (LPS). Both aromatic rings (F5, F6, F17, and F27) and
      interfacial basic amino acids of LL-37 directly interact with anionic
      phosphatidylglycerols (PG). Although the peptide sequences reported in the
      literature vary slightly, there is a consensus that the central helix of LL-37 is
      essential for disrupting superbugs (e.g., MRSA), bacterial biofilms, and viruses
      such as human immunodeficiency virus 1 (HIV-1) and respiratory syncytial virus
      (RSV). In the central helix, the central arginine R23 is of particular importance
      in binding to bacterial membranes or DNA. Mapping the functional roles of the
      cationic amino acids of the major antimicrobial region of LL-37 provides a basis
      for designing antimicrobial peptides with desired properties. This article is
      part of a Special Issue entitled: Interfacially Active Peptides and Proteins.
      Guest Editors: William C. Wimley and Kalina Hristova. 

PMID- 24463072
TI  - Bladder tissue permeability and transport modelling of intravesical alum,
      lidocaine hydrochloride, methylprednisolone hemisuccinate and mitomycin C.
AB  - The aims of this study were to assess the tissue permeability of the bladder and
      to characterize the transport of four drugs displaying different physico-chemical
      properties and commonly used in intravesical delivery, through porcine bladder.
      The transport of aluminium through porcine bladder was assessed by using a
      vertical static diffusion cell. Lidocaine hydrochloride, methylprednisolone
      hemisuccinate and mitomycin C were tested by using three different experimental
      setups, including vertical static diffusion cell, microdialyseur and lab-patented
      device. Penetration results on different experimental setups were homogenous
      suggesting dependency on physico-chemical characteristics of drug and subsequent
      interaction with bladder wall structure. Oppositely, permeation varied
      consistently with experimental setup characteristics (i.e., permeation surface,
      receptor fluid volume and hydrodynamic). Mathematical modelling of drug transport
      through bladder wall is proposed considering scarce literature on this route of
      administration. Practical outcome of this study could drive compounding
      optimization towards improvement of safety and efficacy in patient undergoing
      intravesical administration. 

PMID- 24463073
TI  - Folate-decorated PEG-PLGA nanoparticles with silica shells for capecitabine
      controlled and targeted delivery.
AB  - Di-block polymer of poly (lactic-co-glycolic acid)-poly (ethylene glycol) (PLGA
      PEG) end-capped with capecitabine (CAP) at the hydrophobic domain and folate (FA)
      at hydrophilic domain were synthesized respectively. The products were
      extensively studied by nuclear magnetic resonance ((1)H NMR) and gel permeation
      chromatography (GPC) measurement. By using emulsion-solvent evaporation method,
      the two conjugates, drug CAP and tetramethoxysilane (TMOS) were mixed to form the
      CAP entrapped nanoparticles (NPs) with the FA moieties exposed on NPs surface,
      while simultaneously forming a cross-linked silica shell out of hydrophobic PLGA
      core domain. The testing results showed the CAP-loaded NPs presented suitable
      physical stability, favorable size around 200 nm, negative zeta potential charge
      (-28.43 +/- 2.55 mV) and high encapsulation efficiency (69%). Both silica shell
      cross-linked drug-loaded NPs (SSCL NPs) and none silica shell cross-linked NPs
      (NSSCL NPs) provided an initial burst release and followed by a sustained two
      stage release of the CAP. Straight lines approximate the steady-state for the two
      stage release, and the K/K' of the two stages are 1.96304 and 1.78697
      respectively suggesting the silica shell influenced the release of first stage
      significantly.

PMID- 24463074
TI  - Graft cholangiopathy: etiology, diagnosis, and therapeutic strategies.
AB  - BACKGROUND: Graft cholangiopathy has been recognized as a significant cause of
      morbidity, graft loss, and even mortality in patients after orthotopic liver
      transplantation. The aim of this review is to analyze the etiology, pathogenesis,
      diagnosis and therapeutic strategies of graft cholangiopathy after liver
      transplantation. DATA SOURCE: A PubMed database search was performed to identify
      articles relevant to liver transplantation, biliary complications and
      cholangiopathy. RESULTS: Several risk factors for graft cholangiopathy after
      liver transplantation have been identified, including ischemia/reperfusion
      injury, cytomegalovirus infection, immunological injury and bile salt toxicity. A
      number of strategies have been attempted to prevent the development of graft
      cholangiopathy, but their efficacy needs to be evaluated in large clinical
      studies. Non-surgical approaches may offer good results in patients with
      extrahepatic lesions. For most patients with complex hilar and intrahepatic
      biliary abnormalities, however, surgical repair or re-transplantation may be
      required. CONCLUSIONS: The pathogenesis of graft cholangiopathy after liver
      transplantation is multifactorial. In the future, more efforts should be devoted
      to the development of more effective preventative and therapeutic strategies
      against graft cholangiopathy.

PMID- 24463075
TI  - Graft-to-recipient weight ratio lower to 0.7% is safe without portal pressure
      modulation in right-lobe living donor liver transplantation with favorable
      conditions.
AB  - BACKGROUND: The low graft-to-recipient weight ratio (GRWR) in adult-to-adult
      living donor liver transplantation (LDLT) is one of the major risk factors
      affecting graft survival. The goal of this study was to evaluate whether the
      lower limit of the GRWR can be safely reduced without portal pressure modulation
      in right-lobe LDLT. METHODS: From 2005 to 2011, 317 consecutive patients from a
      single institute underwent LDLT with right-lobe grafts without portal pressure
      modulation. Of these, 23 had a GRWR of less than 0.7% (group A), 27 had a GRWR of
      >=0.7%, <0.8% (group B), and 267 had a GRWR of more than and equal to 0.8% (group
      C). Medical records, including recipient, donor, operation factors, laboratory
      findings and complications were reviewed retrospectively. RESULTS: The baseline
      demographics showed low model for end-stage liver disease score (mean 16.3+/-8.9)
      and high percentage of hepatocellular carcinoma (231 patients, 72.9%). Three
      groups by GRWR demonstrated similar characteristics except recipient body mass
      index and donor gender. For small-for-size syndrome, there were 3 (13.0%) in
      group A, 1 (3.7%) in group B, and 2 patients (0.7%) in group C (P<0.001). Hepatic
      artery thrombosis was more frequently observed in group A than in groups B and C
      (8.7% vs 3.7% vs 1.9%, P=0.047). However, among the three groups, graft survival
      rates at 1 year (100% vs 96.3% vs 93.6%) and 3 years (91.7% vs 73.2% vs 88.1%)
      were not different (P=0.539). In laboratory measurements, there was no group
      difference in total bilirubin and albumin. However, prothrombin time was longer
      in group A within postoperative 1 week and platelet count was lower in groups A
      and B within postoperative 1 month. CONCLUSION: A GRWR lower to 0.7% is safe and
      does not need to modulate portal pressure in adult-to-adult LDLT using the right
      lobe in favorable conditions including low model for end-stage liver disease
      score.

PMID- 24463076
TI  - Platelet count reduction and outcomes in living liver donors.
AB  - BACKGROUND: Platelet count reduction in living donors after graft harvesting is
      very common. The mechanisms and the subsequent adverse consequences are not
      clear. The present study was to explore the mechanisms and the consequences of
      platelet count reduction in living donors. METHODS: We collected data from 231
      living liver donor patients who donated at our transplant center between July
      2002 and August 2009. Baseline and post-operative platelet counts were collected
      and analyzed. Multivariate logistic regression analysis was used to compare the
      risk factors for the persistent decrease in platelet counts. Complications and
      other post-operative recovery were compared between the donors. RESULTS: Platelet
      count decreased differently at each of the follow-up intervals, and the average
      reduction from baseline evaluation to year 3 was 18.2%. A concomitant decrease in
      white blood cells was observed with platelet count reduction. All of the splenic
      volumes at the post-operative follow-up time points were significantly higher
      than those at baseline (P<0.01). Multivariate logistic regression analysis
      indicated that the graft-to-donor weight ratio was a risk factor for low post
      operative platelet counts in living donors at the three follow-up time points:
      one week (P=0.047), one month (P=0.034), and three months (P=0.047). At the one
      week follow-up time, 77 donor platelet counts were higher (group 1) and 151 donor
      platelet counts were lower (group 2) than baseline levels. Two hemorrhage events
      (1.3%) were observed in group 2, while three hemorrhage events (3.9%) were
      observed in group 1 (P=0.211). The overall complication rate was comparable
      between the two groups (P=0.972). CONCLUSION: An increase in harvesting graft may
      decrease platelet counts, but this reduction does not produce short- or long-term
      damage in living liver donors.

PMID- 24463077
TI  - Genome-wide microarray-based analysis of miRNAs expression in patients with acute
      on-chronic liver failure.
AB  - BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome
      that may cause a high mortality. However, the mechanism is still not clear.
      Characterization of the microRNA (miRNA) profiles in ACLF patients may provide
      new clues to the pathogenesis and management of this syndrome. METHODS: Genome
      wide microarray was performed to compare the different miRNA expression profiles
      in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF
      patient and an HBV asymptomatic carrier (AsC). The case-control miRNA profiles
      were compared and confirmed by quantitative reverse transcription-polymerase
      chain reaction in 104 ACLF patients and 96 AsCs. A combined computational
      prediction algorithm was used to predict the potential target genes. RESULTS:
      Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF
      group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and
      8.63-fold in ACLF patients compared with that in AsCs, respectively (P<0.001).
      CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of
      hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes
      of hsa-let-7a. CONCLUSIONS: Our results showed that there is a close relationship
      between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR
      16 and hsa-let-7a may contribute to the development of ACLF.

PMID- 24463078
TI  - Hepatic ischemic preconditioning increases portal vein flow in experimental liver
      ischemia reperfusion injury.
AB  - BACKGROUND: Ischemic preconditioning (IPC) has been shown to decrease liver
      injury and to increase hepatic microvascular perfusion after liver ischemia
      reperfusion. This study aimed to evaluate the effects of IPC on hemodynamics of
      the portal venous system. METHODS: Thirty-two rats were randomized into two
      groups: IPC group and control group. The rats of the IPC group underwent IPC by
      10 minutes of liver ischemia followed by 10 minutes of reperfusion before liver
      ischemia, and the rats of the control group were subjected to 60 minutes of
      partial liver ischemia. Non-ischemic lobes were resected immediately after
      reperfusion. The animals were studied at 4 hours and 12 hours after reperfusion.
      Mean arterial pressure, heart rate, portal vein flow and pressure were analyzed.
      Blood was collected for the determination of the levels of aspartate
      aminotransferase, alanine aminotransferase, calcium, lactate, pH, bicarbonate,
      and base excess. RESULTS: IPC increased the mean portal vein flow at 4 hours and
      12 hours after reperfusion. IPC recovered 78% of the mean portal vein flow at 12
      hours after reperfusion. IPC decreased the levels of aspartate aminotransferase,
      alanine aminotransferase and lactate, and increased the levels of ionized
      calcium, bicarbonate and base excess at 12 hours after reperfusion. CONCLUSIONS:
      This study demonstrated that IPC increases portal vein flow and enhances
      hepatoprotective effects in liver ischemia reperfusion. The better recovery of
      portal vein flow after IPC may be correlated with the lower levels of
      transaminases and with the better metabolic profile.

PMID- 24463079
TI  - ZBTB20 is involved in liver regeneration after partial hepatectomy in mouse.
AB  - BACKGROUND: A better understanding of the molecular mechanisms in liver
      regeneration holds promise for exploring the new potential therapy for liver
      failure. The present study was to investigate the role of zinc finger and BTB
      domain-containing protein 20 (ZBTB20), a potential factor associated with liver
      regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for
      liver proliferation such as liver/body ratio and BrdU positivity were obtained
      via direct measurement and immunohistochemistry. The levels of zinc fingers and
      homeoboxes 2 (ZHX2), ZBTB20, alpha-fetoprotein (AFP) and glypican 3 (GPC3)
      transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model
      were monitored by real-time PCR analysis at different time points. Knockdown of
      ZBTB20 was performed to characterize its regulatory function. RESULTS: A
      negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was
      revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively
      regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the
      proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In
      addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration
      and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and
      GPC3 expression.

PMID- 24463080
TI  - Sequential embolization of the branches of the bile duct and portal vein to the
      targeted hepatic lobe in rats.
AB  - BACKGROUND: The high recurrence rate of hepatolithiasis and the high operative
      risk of right posterior, caudate or multiple lobe hepatectomy are the unsettled
      problems in hepatobiliary surgery. The present study was to investigate the
      efficacy of chemical hepatectomy performed via applying sequential embolization
      of the branches of the bile duct and portal vein to the targeted hepatic lobe.
      METHODS: The bile duct and portal vein branches of the median hepatic lobe of
      rats were treated with: 1) bile duct embolization followed by portal vein
      ligation (BDE+PVL) and 2) portal vein ligation followed by bile duct embolization
      (PVL+BDE). The efficacy of chemical hepatectomy in BDE+PVL and PVL+BDE groups was
      compared with that of sole BDE by histology and Western blotting analysis of
      collagen I expression. RESULTS: After six weeks of the chemical hepatectomy, rats
      in the BDE group showed hepatocyte damages, fibrosis and "self-cut" only in the
      periphery of the embolized lobe. In contrast, rats in the PVL+BDE and BDE+PVL
      groups exhibited complete necrosis of hepatocytes and replacement with
      proliferative ductules and collagen fibers, leading to complete fibrosis and
      "self-cut" phenomenon in the whole targeted lobe. Collagen I expression in the
      PVL+BDE group was slightly higher than that in the BDE+PVL group; however, no
      statistically significant difference was noted. CONCLUSION: The sequential
      embolization of the bile duct and portal vein branches to the targeted hepatic
      lobe may be a feasible and effective approach to acheive the ideal effect of
      chemical hepatectomy in a short period of time.

PMID- 24463081
TI  - Direct peroral cholangioscopy using an ultraslim upper endoscope for biliary
      lesions.
AB  - BACKGROUND: The development of direct peroral cholangioscopy (DPOC) using an
      ultraslim endoscope simplifies biliary cannulation. The conventional techniques
      are cumbersome to perform and require advanced skills. The recent introduction of
      the guidewires and balloons has improved the therapeutic outcomes. Here we
      describe an effective and easier method for performing DPOC using an ultraslim
      upper endoscope. METHODS: Indications for DPOC were the presence of stones on
      follow-up of patients who had previously undergone complete sphincteroplasty,
      including endoscopic sphincterotomy or endoscopic papillary large balloon
      dilatation. Fifteen patients underwent DPOC. An ultraslim endoscope was inserted
      perorally and was advanced into the major papilla. The ampulla of Vater was
      visualized by retroflexing the endoscope in the distal second portion of the
      duodenum, and then DPOC was performed using a wire-guided cannulation technique
      with an anchored intraductal balloon catheter. RESULTS: One patient failed in the
      treatment due to looping of the endoscope in the fornix of the stomach. Fourteen
      (93.3%) were successfully treated with our modified DPOC technique. Only one
      patient (6.7%) experienced an adverse event (pancreatitis) who responded well to
      conservative management. Residual stones of the common bile duct were completely
      removed in 3 patients. CONCLUSION: The modified method of DPOC is simple, safe
      and easy to access the bile duct.

PMID- 24463082
TI  - Pravastatin activates the expression of farnesoid X receptor and liver X receptor
      alpha in Hep3B cells.
AB  - BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing
      pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder
      epithelial cells. They also affect cross-talk among the nuclear hormone receptors
      that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes.
      However, there is controversy over whether or how statins change the expression
      of peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, liver X
      receptor alpha (LXRalpha), farnesoid X receptor (FXR), ABCG5, ABCG8, and 7alpha
      hydroxylase (CYP7A1) which are directly involved in the cholesterol saturation
      index in bile. METHODS: Human Hep3B cells were cultured on dishes. MTT assays
      were performed to determine the appropriate concentrations of reagents to be
      used. The protein expression of PPARalpha and PPARgamma was measured by Western
      blotting analysis, and the mRNA expression of LXRalpha, FXR, ABCG5, ABCG8 and
      CYP7A1 was estimated by RT-PCR. RESULTS: In cultured Hep3B cells, pravastatin
      activated PPARalpha and PPARgamma protein expression, induced stronger expression
      of PPARgamma than that of PPARalpha, increased LXRalpha mRNA expression,
      activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRalpha,
      enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by
      the PPARgamma and LXRalpha pathways, together or independently. CONCLUSION: Our
      data suggested that pravastatin prevents cholesterol gallstone diseases via the
      increase of FXR, LXRalpha and CYP7A1 in human hepatocytes.

PMID- 24463083
TI  - Blood group type antigens in pancreatic intraductal papillary mucinous neoplasms.
AB  - BACKGROUND: There are few data on blood group (BG) types and types of pancreatic
      cancers. The aims of this study were to study BG types and BG-antigens in
      pancreatic intraductal papillary mucinous neoplasms (IPMNs). METHODS: BG type and
      tumor BG-antigen (glycoprotein) expression (studied by immunohistochemistry on
      tissue microarrays) were analyzed with regard to characteristics of 101
      surgically resected pancreatic IPMNs. RESULTS: Non-O BG type predicted invasive
      carcinoma independently from high serum CA19-9 and male gender. BG type A was
      observed more frequently in women than in men. Chronic pancreatitis was more
      frequently seen in patients with BG type B or AB. Aberrant tumor expression (with
      regard to BG type) of loss of A antigen expression type occurred in 15.0% of
      IPMNs and of loss of B antigen expression type in 62.5% of IPMNs. Intraneoplasm
      BG-antigen expression was not related to dysplasia grade or invasion. CONCLUSION:
      The results of the study suggest that in pancreatic IPMN, non-O BG type predicted
      invasive carcinoma, whereas for intratumor BG-antigen expression no specific
      patterns were detected with regard to the progression of glandular epithelial
      dysplasia or invasion.

PMID- 24463084
TI  - Effect of CD74 on the prognosis of patients with resectable pancreatic cancer.
AB  - BACKGROUND: CD74 is known as a type II transmembrane glycoprotein that is
      associated with the major histocompatibility complex class II alpha and beta
      chains. Recent studies have demonstrated that the expression of CD74 is also
      linked to some forms of tumors. The present study was to assess the effect of
      CD74 expression on the prognosis of resectable pancreatic ductal adenocarcinoma
      (PDAC). METHODS: Forty-six patients who had received a curative resection of
      primary PDAC and postoperative chemotherapy were included in this study.
      Immunohistochemical staining was conducted of CD74 on paraffin-embedded tumor
      sample slices. The patients were grouped according to CD74 staining: CD74 (-):
      CD74 positive tumor cells<25%; and CD74 (+): CD74 positive tumor cells >=25%. The
      correlation of CD74 expression level with clinicopathological features and
      cumulative survival rate was calculated. RESULTS: The numbers of CD74 (+) and (-)
      patients were 32 and 14, respectively. CD74 (+) patients showed a high rate of
      perineural invasion (P=0.007). The 3- and 5-year cumulative survival rates of
      CD74 (-) patients were significantly higher than those of CD74 (+) patients (62%
      and 41% vs 9% and 0%, P=0.000). Multivariate analysis showed that CD74 expression
      and lymphatic permeation were the independent prognostic indicators. CONCLUSIONS:
      The overexpression of CD74 is a key factor associated with perineural invasion.
      Lower-stage (I and II) PDAC patients with CD74 overexpression have a poor
      prognosis even if they receive a curative resection. CD74 can be used as a
      prognostic indicator for resectable PDAC.

PMID- 24463085
TI  - KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in
      vivo.
AB  - BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but
      its mechanism is not clear. The present study aimed to determine the role of KAI1
      in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1
      gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1
      by using liposomes and selected by G418, and the protein was measured by Western
      blotting. After successful infection, the cell growth curve was studied by MTT,
      vascular endothelial growth factor C (VEGF-C) secretion by pancreatic cancer cell
      were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were
      renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected
      into the subcuticular layer of nude mice; both tumor growth and metastasis
      through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was
      measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly
      reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected
      with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the
      injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors
      showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa
      2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the
      lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

PMID- 24463086
TI  - Novel en-bloc resection of locally advanced hilar cholangiocarcinoma: the Rex
      recess approach.
AB  - Loco-regional recurrence after potentially curative resection remains a problem
      in hilar cholangiocarcinoma. Hilar dissection risks local spillage of tumor cells
      leading to suboptimal disease free survival. We have developed a new technique of
      radical resection for hilar cholangiocarcinoma based on the distinctive anatomy
      of the Rex recess of the liver, which has been assessed in two patients with
      locally advanced hilar cholangiocarcinoma. This technique included a right
      hepatectomy with en-bloc resection of the hepatoduodenal ligament and portal
      venous reconstruction to the left portal vein at the Rex recess. Both patients
      had R0 resection and have been disease-free for 26 and 38 months, respectively. 

PMID- 24463087
TI  - Complex hepatic outflow reconstruction in domino liver transplantation.
AB  - Domino liver transplantation has been accepted as a safe procedure to further
      expand the organ donor pool. The most important technical challenge of the
      procedure resides in restoring a proper hepatic venous allograft outflow in the
      familial amyloidotic polyneuropathy-liver recipient. To overcome this issue,
      combined techniques were used to perform an innovative outflow reconstruction. A
      domino liver transplantation was successfully performed with reconstruction of
      complex venous outflow. The inferior vena cava sparing hepatectomy technique in
      the familial amyloidotic polyneuropathy-donor was used to cut the hepatic vein to
      the liver parenchyma. To overcome this issue the venous outflow tract was
      reconstructed using a longitudinally opened iliac vein graft from a post-mortem
      donor to create a new outflow tract using a diamond patch between the right and
      middle/left hepatic veins. 

PMID- 24463088
TI  - Intrahepatic Glissonian approach and outflow vascular occlusion during partial
      hepatectomy.
AB  - Under ultrasound guidance, a blunt suture needle was inserted around the
      Glissonian pedicle and then sutured. This technique significantly reduced the
      blood loss and facilitated the procedure of partial hepatectomy. We applied this
      technique in 182 patients who needed partial hepatectomy. We concluded that this
      method is simple and easy to occlude the vascular inflow and outflow, and allows
      an accurate delineation of the anatomic zone and therefore, simplifies the
      procedure of partial hepatectomy. 

PMID- 24463089
TI  - Samaritan donor interchange in living donor liver transplantation.
AB  - BACKGROUND: In order to overcome ABO blood group incompatibility, paired donor
      interchange has been practised in living donor liver transplantation. Liver
      transplantations using grafts donated by Samaritan living donors have been
      performed in Europe, North America, South Korea, and Hong Kong. Such practice is
      clearly on strong biological grounds although social and psychological
      implications could be far-reaching. Local experience has been satisfactory but is
      still limited. As few centers have this arrangement, its safety and viability are
      still being assessed under a clinical trial setting. METHODS: Here we report a
      donor interchange involving an ABO-compatible pair with a universal donor and an
      ABO-incompatible pair with a universal recipient. This matching was not only a
      variation but also an extension of the donor interchange scheme. RESULTS: The
      four operations (two donor hepatectomies and two recipient operations) were
      successful. All the two donors and the two recipients recovered well. Such donor
      interchange further supports the altruistic principle of organ donation in
      contrast to exchange for a gain. CONCLUSIONS: Samaritan donor interchange
      certainly taxes further the ethical challenge of donor interchange. Although this
      practice has obvious biological advantages, such advantages have to be weighed
      against the potential increase in potential psychological risks to the subjects
      in the interchange. Further ethical and clinical evaluations of local and
      overseas experiences of donor interchange should guide future clinical practice
      in utilizing this potential organ source for transplantation.

PMID- 24463090
TI  - Boron increases the cell viability of mesenchymal stem cells after long-term
      cryopreservation.
AB  - The field of stem-cell biology has emerged as a key technology for the treatment
      of various disorders and tissue regeneration applications. However, a major
      problem remains in clinical practice, which is the question of whether stem cells
      preserve their self-renewal and differentiation potential in the culture
      conditions or not. In the current study, effects of boron on the cryopreservation
      of human tooth germ stem cells (hTGSCs) were evaluated for the first time. The
      impacts of various boron concentrations (sodium pentaborate pentahydrate (NaB))
      were tested on characterized hTGSCs viability for different time intervals (24,
      48, and 72 h). 20 MUg/ml NaB with lower Me(2)SO concentration was found to
      display positive effects on hTGSCs during repeated freezing and defrosting
      cycles, and long-term cryopreservation. After thawing, cells were analyzed for
      their surface antigens and differentiation capacity. hTGSCs were successfully
      cryopreserved without any change in their mesenchymal stem cell characteristics
      as they were treated with boron containing freezing medium. In addition, fatty
      acid composition was examined to demonstrate membrane fatty acid profiles after
      freeze-thawing. Besides, NaB treatment extended osteogenic and chondrogenic
      differentiation of hTGSCs remarkably after long-term cryopreservation with
      respect to control groups. The study clearly suggests that NaB has a protective
      role on the survival of hTGSCs in short- and long-term cryopreservation. Due to
      the possible storage of hTGSCs at early ages, development of a functional and
      reliable cryopreservation media can be designed as a future solution to the
      dental stem cell banking.

PMID- 24463091
TI  - Cryotherapy for local recurrent dermatofibrosarcoma protuberans: experience in 19
      patients.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive, cutaneous,
      malignant tumor characterized by a high propensity for local relapse. Wide and
      deep local excision with reconstructive surgery is the current standard therapy
      for DFSP, with a local recurrence rate (LRR) of nearly 40%. In this study, we
      cured 19 patients with local recurrence of DFSP with 39 sessions of percutaneous
      cryoablation performed between July 2004 and August 2008. The LRRs after one, two
      and three cryosurgery sessions per patient were 68%, 54% and 0%, respectively.
      Moreover, the LRR did not differ with tumor location or size. Furthermore, all
      patients had a progression-free survival of >5 years. Only minor complications
      such as fever, local edema, mild nerve injury and local pain occurred, and were
      resolved within 1 week with symptomatic treatment. In our experience,
      percutaneous cryoablation is a relatively safe and efficient technique for the
      treatment of local recurrence of DFSPs.

PMID- 24463092
TI  - Developmental competence of frozen-thawed yak (Bos grunniens) oocytes followed by
      in vitro maturation and fertilization.
AB  - In the present study, we examined the ability of immature germinal vesicle (GV)
      and subjected to in vitro matured (MII) yak oocytes to survive after
      cryopreservation as well as their subsequent development following in vitro
      maturation and fertilization. Both GV and MII oocytes were cryopreserved by using
      two different vitrification solutions (VS); VS-I contained 10% ethylene glycol
      (EG) and 10% dimethylsulfoxide (DMSO) in TCM-199 + 20% (v/v) fetal calf serum
      (FCS) whereas VS-II contained 40% EG + 18% Ficoll + 0.5 M sucrose in TCM-199 +
      20% FCS. The percentage of oocytes found to be morphologically normal was greater
      (P < 0.01) in VS-I group than in VS-II group. Rates of cleavage (30.6-42.2%) and
      blastocyst formation (2.9-8.9%) did not differ among groups, but were lower than
      in unfrozen control (55.7% and 25.4%, P < 0.01). These results show that a
      combination of EG and DMSO or EG, Ficoll and sucrose can be used to cryopreserve
      yak oocytes in French straws.

PMID- 24463093
TI  - Rhodotorula svalbardensis sp. nov., a novel yeast species isolated from
      cryoconite holes of Ny-Alesund, Arctic.
AB  - A psychrophilic yeast species was isolated from glacier cryoconite holes of
      Svalbard. Nucleotide sequences of the strains were studied using D1/D2 domain,
      ITS region and partial sequences of mitochondrial cytochrome b gene. The strains
      belonged to a clade of psychrophilic yeasts, but showed marked differences from
      related species in the D1/D2 domain and biochemical characters. Effects of
      temperature, salt and media on growth of the cultures were also studied.
      Screening of the cultures for amylase, cellulase, protease, lipase, urease and
      catalase activities was carried out. The strains expressed high amylase and
      lipase activities. Freeze tolerance ability of the isolates indicated the
      formation of unique hexagonal ice crystal structures due to presence of
      'antifreeze proteins' (AFPs). FAME analysis of cultures showed a unique trend of
      increase in unsaturated fatty acids with decrease in temperature. The major fatty
      acids recorded were oleic acid, linoleic acid, linolenic acid, palmitic acid,
      stearic acid, myristic acid and pentadecanoic acid. Based on sequence data and,
      physiological and morphological properties of the strains, we propose a novel
      species, Rhodotorula svalbardensis and designate strains MLB-I (CCP-II) and CRY
      YB-1 (CBS 12863, JCM 19699, JCM 19700, MTCC 10952) as its type strains
      (Etymology: sval.bar.den'sis. N.L. fem. adj. svalbardensis pertaining to
      Svalbard). 

PMID- 24463094
TI  - Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related
      events induced by breast cancer bone metastases and treatment.
AB  - Many breast cancer patients experience bone metastases and suffer skeletal
      complications. The present study provides evidence on the protective and
      therapeutic potential of betulinic acid on cancer-associated bone diseases.
      Betulinic acid is a naturally occurring triterpenoid with the beneficial activity
      to limit the progression and severity of cancer, diabetes, cardiovascular
      diseases, atherosclerosis, and obesity. We first investigated its effect on
      breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of
      osteolytic bone metastasis. Betulinic acid reduced cell viability and the
      production of parathyroid hormone-related protein (PTHrP), a major osteolytic
      factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or
      without tumor growth factor-beta. Betulinic acid blocked an increase in the
      receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio
      by downregulating RANKL protein expression in PTHrP-treated human osteoblastic
      cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in
      murine bone marrow macrophages and decreased the production of resorbed area in
      plates with a bone biomimetic synthetic surface by suppressing the secretion of
      matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced
      osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone
      loss in mice intra-tibially inoculated with breast cancer cells and in
      ovariectomized mice causing estrogen deprivation, as supported by the restored
      bone morphometric parameters and serum bone turnover markers. Taken together,
      these findings suggest that betulinic acid may have the potential to prevent bone
      loss in patients with bone metastases and cancer treatment-induced estrogen
      deficiency. 

PMID- 24463095
TI  - In silico prediction of toxicity of non-congeneric industrial chemicals using
      ensemble learning based modeling approaches.
AB  - Ensemble learning approach based decision treeboost (DTB) and decision tree
      forest (DTF) models are introduced in order to establish quantitative structure
      toxicity relationship (QSTR) for the prediction of toxicity of 1450 diverse
      chemicals. Eight non-quantum mechanical molecular descriptors were derived.
      Structural diversity of the chemicals was evaluated using Tanimoto similarity
      index. Stochastic gradient boosting and bagging algorithms supplemented DTB and
      DTF models were constructed for classification and function optimization problems
      using the toxicity end-point in T. pyriformis. Special attention was drawn to
      prediction ability and robustness of the models, investigated both in external
      and 10-fold cross validation processes. In complete data, optimal DTB and DTF
      models rendered accuracies of 98.90%, 98.83% in two-category and 98.14%, 98.14%
      in four-category toxicity classifications. Both the models further yielded
      classification accuracies of 100% in external toxicity data of T. pyriformis. The
      constructed regression models (DTB and DTF) using five descriptors yielded
      correlation coefficients (R(2)) of 0.945, 0.944 between the measured and
      predicted toxicities with mean squared errors (MSEs) of 0.059, and 0.064 in
      complete T. pyriformis data. The T. pyriformis regression models (DTB and DTF)
      applied to the external toxicity data sets yielded R(2) and MSE values of 0.637,
      0.655; 0.534, 0.507 (marine bacteria) and 0.741, 0.691; 0.155, 0.173 (algae). The
      results suggest for wide applicability of the inter-species models in predicting
      toxicity of new chemicals for regulatory purposes. These approaches provide
      useful strategy and robust tools in the screening of ecotoxicological risk or
      environmental hazard potential of chemicals. 

PMID- 24463096
TI  - Maternal glucocorticoid elevation and associated blood metabonome changes might
      be involved in metabolic programming of intrauterine growth retardation in rats
      exposed to caffeine prenatally.
AB  - Our previous studies demonstrated that prenatal caffeine exposure causes
      intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels
      of maternal glucocorticoids (GC), and intrauterine metabolic programming and
      associated metabonome alteration that may be GC-mediated. However, whether
      maternal metabonomes would be altered and relevant metabolite variations might
      mediate the development of IUGR remained unknown. In the present studies, we
      examined the dose- and time-effects of caffeine on maternal metabonome, and tried
      to clarify the potential roles of maternal GCs and metabonome changes in the
      metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with
      caffeine (0, 20, 60 or 180 mg/kg.d) from gestational days (GD) 11 to 20, or 180
      mg/kg.d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose
      effect study and on GD11, 14 and 17 in the time-course study were analyzed by 1H
      nuclear magnetic resonance spectroscopy, respectively. Caffeine administration
      reduced maternal weight gains and elevated both maternal and fetal corticosterone
      (CORT) levels. A negative correlation between maternal/fetal CORT levels and
      fetal bodyweight was observed. The maternal metabonome alterations included
      attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown,
      and amino acid accumulation, suggesting GC-associated metabolic effects. GC
      associated metabolite variations (alpha/beta-glucoses, high density lipoprotein
      cholesterol, beta-hydroxybutyrate) were observed early following caffeine
      administration. In conclusion, prenatal caffeine exposure induced maternal GC
      elevation and metabonome alteration, and maternal GC and relevant discriminatory
      metabolites might be involved in the metabolic programming of caffeine-induced
      IUGR.

PMID- 24463097
TI  - Fabrication and evaluation of the novel reduction-sensitive starch nanoparticles
      for controlled drug release.
AB  - A novel type of reduction-sensitive starch nanoparticles was prepared via the
      reversed-phase microemulsion method by using crosslinker, N,N
      bisacryloylcystamine (BAC) with the disulfide linkages, which was specifically
      cleaved by dithiothreitol (DTT). Starch nanoparticles had a spherical morphology
      with a small size of 40 nm in the optimal condition. The influences of process
      parameters (starch amount, surfactant amount and oil/water (O/W) ratio) on the
      size of starch nanoparticles were studied by dynamic light scattering (DLS). BAC
      crosslinked starch nanoparticles were degraded into oligomers with the reducing
      agent of DTT due to the cleavage of the disulfide linkages. A model drug 5
      aminosalicylic acid (5-ASA) could be loaded efficiently into starch nanoparticles
      and the in vitro drug release behaviors were also studied. The results suggested
      that the disulfide crosslinked starch nanoparticles exhibited an accelerated drug
      release behavior in the presence of DTT. In vitro methyl thiazolyl tetrazolium
      (MTT) assays indicated that BAC crosslinked starch nanoparticles had a good
      biocompatibility when cocultured with human HeLa cancer cells. Hence, with
      excellent biocompatibility and biodegradability, and rapid drug release in
      response to DTT, BAC crosslinked starch nanoparticles showed a great potential as
      a biomaterial carrier for the application of drug controlled release. In contrast
      to BAC crosslinked starch nanoparticles, N,N-methylenebisacrylamine (MBA)
      crosslinked starch nanoparticles were prepared as the control without the
      disulfide linkages.

PMID- 24463098
TI  - Sensitivity of human granulosa cell tumor cells to epidermal growth factor
      receptor inhibition.
AB  - Epidermal growth factor receptor (EGFR) is implicated in the progression of many
      human cancers, but its significance in ovarian granulosa cell tumor (GCT)
      pathobiology remains poorly understood. We assessed the EGFR gene copy number,
      surveyed the mRNA and protein expression patterns of EGFR in 90 adult GCTs, and
      assessed the in vitro sensitivity of GCT cells to EGFR inhibition. Low-level
      amplification of EGFR gene was observed in five GCTs and high-level amplification
      in one sample. EGFR mRNA was robustly expressed in GCTs. Most tumors expressed
      both unphosphorylated and phosphorylated EGFR protein, but the protein expression
      did not correlate with clinical parameters, including the risk of recurrence.
      Small-molecule EGFR inhibitors reduced the EGF-induced activation of EGFR and its
      downstream signaling molecules at nanomolar doses, but cell viability was
      reduced, and caspase-3/7 was activated in GCT cells only at micromolar doses.
      Based on the present results, EGFR is active and abundantly expressed in the
      majority of GCTs, but probably has only minor contribution to GCT cell growth.
      Given the high doses of EGFR inhibitors required to reduce GCT cell viability in
      vitro, they are not likely to be effective for GCT treatment as single agents;
      they should rather be tested as part of combination therapies for these
      malignancies. 

PMID- 24463099
TI  - Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and
      liver.
AB  - Obesity and secondary development of type 2 diabetes (T2D) are major health care
      problems throughout the developed world. Accumulating evidence suggest that
      glycerol metabolism contributes to the pathophysiology of obesity and T2D.
      Glycerol is a small molecule that serves as an important intermediate between
      carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as
      the backbone of triglyceride (TG) and during states of metabolic stress, such as
      fasting and diabetes, it is released for metabolism in other tissues. In the
      liver, glycerol serves as a gluconeogenic precursor and it is used for the
      esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue
      and AQP9 in the liver are transmembrane proteins that belong to the subset of
      AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from
      adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose
      tissue and adult onset obesity. On the other hand, AQP9 expressed in liver
      facilitates the hepatic uptake of glycerol and thereby the availability of
      glycerol for de novo synthesis of glucose and TG that both are involved in the
      pathophysiology of diabetes. The aim of this review was to summarize the current
      knowledge on the role of the two glycerol channels in controlling glycerol
      metabolism in adipose tissue and liver. 

PMID- 24463100
TI  - Ventral tegmental area/substantia nigra and prefrontal cortex rodent organotypic
      brain slices as an integrated model to study the cellular changes induced by
      oxygen/glucose deprivation and reperfusion: effect of neuroprotective agents.
AB  - Unveiling the roles of distinct cell types in brain response to insults is a
      partially unsolved challenge and a key issue for new neuroreparative approaches.
      In vivo models are not able to dissect the contribution of residential microglia
      and infiltrating blood-borne monocytes/macrophages, which are fundamentally
      undistinguishable; conversely, cultured cells lack original tissue anatomical and
      functional complexity, which profoundly alters reactivity. Here, we tested
      whether rodent organotypic co-cultures from mesencephalic ventral tegmental
      area/substantia nigra and prefrontal cortex (VTA/SN-PFC) represent a suitable
      model to study changes induced by oxygen/glucose deprivation and reperfusion
      (OGD/R). OGD/R induced cytotoxicity to both VTA/SN and PFC slices, with higher
      VTA/SN susceptibility. Neurons were highly affected, with astrocytes and
      oligodendrocytes undergoing very mild damage. Marked reactive astrogliosis was
      also evident. Notably, OGD/R triggered the activation of CD68-expressing
      microglia and increased expression of Ym1 and Arg1, two markers of
      "alternatively" activated beneficial microglia. Treatment with two well-known
      neuroprotective drugs, the anticonvulsant agent valproic acid and the purinergic
      P2-antagonist PPADS, prevented neuronal damage. Thus, VTA/SN-PFC cultures are an
      integrated model to investigate OGD/R-induced effects on distinct cells and
      easily screen neuroprotective agents. The model is particularly adequate to
      dissect the microglia phenotypic shift in the lack of a functional vascular
      compartment. 

PMID- 24463101
TI  - Hypoxic preconditioning reinforces cellular functions of autologous peripheral
      blood-derived cells in rabbit hindlimb ischemia model.
AB  - Peripheral blood mononuclear cell (PBMNC) is one of powerful tools for
      therapeutic angiogenesis in hindlimb ischemia. However, traditional approaches
      with transplanted PBMNCs show poor therapeutic effects in severe ischemia
      patients. In this study, we used autograft models to determine whether hypoxic
      pretreatment effectively enhances the cellular functions of PBMNCs and improves
      hindlimb ischemia. Rabbit PBMNCs were cultured in the hypoxic condition. After
      pretreatment, cell adhesion, stress resistance, and expression of angiogenic
      factor were evaluated in vitro. To examine in vivo effects, we autografted
      preconditioned PBMNCs into a rabbit hindlimb ischemia model on postoperative day
      (POD) 7. Preconditioned PBMNCs displayed significantly enhanced functional
      capacities in resistance to oxidative stress, cell viability, and production of
      vascular endothelial growth factor. In addition, autologous transplantation of
      preconditioned PBMNCs significantly induced new vessels and improved limb blood
      flow. Importantly, preconditioned PBMNCs can accelerate vessel formation despite
      transplantation on POD 7, whereas untreated PBMNCs showed poor vascularization.
      Our study demonstrated that hypoxic preconditioning of PBMNCs is a feasible
      approach for increasing the retention of transplanted cells and enhancing
      therapeutic angiogenesis in ischemic tissue. 

PMID- 24463103
TI  - Potential of gas chromatography-atmospheric pressure chemical ionization-time-of
      flight mass spectrometry for the determination of sterols in human plasma.
AB  - The application of Gas Chromatography (GC)-Atmospheric Pressure Chemical
      Ionization (APCI)-Time-of-Flight Mass Spectrometry (TOF-MS) is presented for
      sterol analysis in human plasma. A commercial APCI interface was modified to
      ensure a well-defined humidity which is essential for controlled ionization. In
      the first step, optimization regarding flow rates of auxiliary gases was
      performed by using a mixture of model analytes. Secondly, the qualitative and
      quantitative analysis of sterols including oxysterols, cholesterol precursors,
      and plant sterols as trimethylsilyl-derivatives was successfully carried out. The
      characteristics of APCI together with the very good mass accuracy of TOF-MS data
      enable the reliable identification of relevant sterols in complex matrices.
      Linear calibration lines and plausible results for healthy volunteers and
      patients could be obtained whereas all mass signals were extracted with an
      extraction width of 20 ppm from the full mass data set. One advantage of high
      mass accuracy can be seen in the fact that from one recorded run any search for
      m/z can be performed.

PMID- 24463102
TI  - Insights into miRNA regulation of the human glycome.
AB  - Glycosylation is an intricate process requiring the coordinated action of
      multiple proteins, including glycosyltransferases, glycosidases, sugar nucleotide
      transporters and trafficking proteins. Work by several groups points to a role
      for microRNA (miRNA) in controlling the levels of specific glycosyltransferases
      involved in cancer, neural migration and osteoblast formation. Recent work in our
      laboratory suggests that miRNA are a principal regulator of the glycome,
      translating genomic information into the glycocode through tuning of enzyme
      levels. Herein we overlay predicted miRNA regulation of glycosylation related
      genes (glycogenes) onto maps of the common N-linked and O-linked glycan
      biosynthetic pathways to identify key regulatory nodes of the glycome. Our
      analysis provides insights into glycan regulation and suggests that at the
      regulatory level, glycogenes are non-redundant.

PMID- 24463104
TI  - Effect of different stapes prostheses on the passive vibration of the basilar
      membrane.
AB  - The effect of different stapes prostheses on the basilar membrane (BM) motion was
      determined. To that end, a three dimensional finite element (FE) model of the
      passive human cochlea was developed. Passive responses of the BM were found based
      on coupled fluid-structure interactions between the cochlear solid structures and
      the scala fluids. The passive BM vibrations in normal (healthy) cochlea were
      compared with vibrations in the cochlea in which a 0.4-mm piston or a proposed
      new type of prosthesis was implanted. The proposed chamber prosthesis was not
      experimentally implanted, but only numerically simulated. Design of the new
      chamber stapes prosthesis is presented for the first time in this paper. The
      simulation results showed 10-20 dB decrease in BM displacement amplitude in the
      case of the piston. In contrast, the BM responses in the cochlea with the new
      prosthesis are higher with respect to the healthy ear. The results obtained in
      this study are promising for further research to optimize the design of the new
      chamber stapes prosthesis. 

PMID- 24463105
TI  - Antileishmanial phytochemical phenolics: molecular docking to potential protein
      targets.
AB  - A molecular docking analysis has been carried out to examine potential Leishmania
      protein targets of antiprotozoal plant-derived polyphenolic compounds. A total of
      352 phenolic phytochemicals, including 10 aurones, six cannabinoids, 34
      chalcones, 20 chromenes, 52 coumarins, 92 flavonoids, 41 isoflavonoids, 52
      lignans, 25 quinones, eight stilbenoids, nine xanthones, and three miscellaneous
      phenolic compounds, were used in the virtual screening study using 24 Leishmania
      enzymes (52 different protein structures from the Protein Data Bank). Noteworthy
      protein targets were Leishmania dihydroorotate dehydrogenase, N-myristoyl
      transferase, phosphodiesterase B1, pteridine reductase, methionyl-tRNA
      synthetase, tyrosyl-tRNA synthetase, uridine diphosphate-glucose
      pyrophosphorylase, nicotinamidase, and glycerol-3-phosphate dehydrogenase. Based
      on in-silico analysis of antiparasitic polyphenolics in this study, two aurones,
      one chalcone, five coumarins, six flavonoids, one isoflavonoid, three lignans,
      and one stilbenoid, can be considered to be promising drug leads worthy of
      further investigation. 

PMID- 24463106
TI  - Hepatic perivascular epithelioid cell tumors-not otherwise specified: a case
      report.
AB  - OBJECTIVE: Neoplasms of perivascular epithelioid cells (PEComas) are
      characterized by epithelioid to spindle cells with eosinophilic to clear
      cytoplasm, an intimate relationship with blood vessels, and coexpression of myoid
      and melanocytic immunohistochemical markers. While most reported hepatic PEComas,
      such as angiomyolipoma (AML), behave in a benign fashion, emerging PEComas cases
      without typical characteristics require further clarification. We report a case
      of primary hepatic perivascular epithelioid cell tumors-not otherwise specified
      (HPEComas-NOS) with untypical pathological and immunohistochemical features
      compared to those of the benign hepatic AML cases. HPEComas-NOS may represent a
      special type of PEComas classified as having "malignant potential" or at "high
      risk of aggressive behavior", suggesting the need for further clarification of
      hepatic PEComas and long-term follow-up of patients with HPEComas-NOS.

PMID- 24463107
TI  - High-throughput microwell plate for cell research.
AB  - OBJECTIVE: We developed a novel simple microwell plate that allows researchers to
      culture cells on chips easily without the use of tubes and pumps for studies of
      cell proliferation, apoptosis and pharmacology. Unlike any other previous design,
      this device can be put into an incubator directly and maintains cells in an
      environment with stable temperature, humidity, air pressure, oxygen and CO2
      concentration. We cultured PC-12 cells in these microwell plates and measured the
      cell proliferation and apoptosis. The microwell plate is recommended for use in
      all research including those involving rare samples and expensive reagents.

PMID- 24463108
TI  - [Ventrolateral periaqueductal gray metabotropic glutamate receptor subtypes 7 and
      8 mediate opposite effects on cardiosomatic motor reflex in rats].
AB  - OBJECTIVE: To investigate the role of ventrolateral periaqueductal gray (VL-PAG)
      metabotropic glutamate receptors subtype 7 and 8 (mGluR 7/8) in descending
      modulation of cardiosomatic motor reflex (CMR) in rats. METHODS: AMN082 (agonist
      of mGluR 7) and DCPG (agonist of mGluR 8) were injected into the VL-PAG of a rat
      model of CMR to observe their effects in modulating CMR. The raphe magnus nucleus
      (NRM) or the gigantocellular reticular nucleus (Gi) was then damaged, and the
      changes in VL-PAG descending modulation were observed. RESULTS: Selective
      activation of mGluR 7 of the VL-PAG by AMN082 obviously facilitated capsaicin
      (CAP)-induced CMR (P<0.05), which was suppressed by DCPG-induced mGluR 8
      activation (P<0.05). These facilitatory or inhibitory effects were completely
      reversed by group III mGluR antagonist MSOP. Damaging the NRM of VL-PAG main
      relay nucleus did not significantly affect the facilitatory effect produced by
      AMN082 microinjection (P>0.05), but partially attenuated the inhibitory effect of
      DCPG microinjection (P<0.05). Both the facilitatory effect of AMN082 and the
      inhibitory effect of DCPG were reduced obviously after bilateral Gi damage
      (P<0.05). CONCLUSION: VL-PAG mGluR 7 and mGluR 8 mediate biphasic regulation of
      CMR in rats probably through activation of different sub-nuclei and different
      neurons in the rostroventral medulla.

PMID- 24463109
TI  - [Foxp3(+)Treg cells mediate immune protection of Humulus pollen allergy DNA
      vaccine pcDNA3.1-Hum in asthmatic mice].
AB  - OBJECTIVE: To construct a humulus pollen allergy DNA vaccine pcDNA3.1-Hum and
      investigate its effect for immune protection mediated by Foxp3(+)Treg cells in
      asthmatic mice. METHODS: The target humulus gene obtained from pTripIEx2-Hum
      plasmid by double enzyme digestion was inserted sequentially into pcDNA3.1(-)
      vector to generate the recombinant plasmid pcDNA3.1-Hum, which was validated by
      sequencing. The pcDNA3.1-Hum plasmid was transfected into COS-7 cells and the
      expression of the ectopic protein was analyzed using Western blotting. Co
      cultured dendritic cells and CD4(+)CD25(-) T cells were stimulated with the
      expressed protein to test its efficacy in inducing Foxp3(+)Treg cells. The levels
      of humulus-specific IgE and IgG2a were assayed to evaluate the allergenicity and
      immunogenicity of pcDNA3.1-Hum in mice. The immunoprotective effect of pcDNA3.1
      Hum was assessed in a mouse model of humulus-specific asthma. RESULTS: The
      constructed pcDNA3.1-Hum plasmid was validated by sequencing and Western
      blotting, and the expressed protein was shown to induce Foxp3(+)Treg cells in the
      co-culture. In normal mice, pcDNA3.1-Hum induced a significant increase of
      humulus-specific IgG2a but had no effect on IgE. In the asthmatic mice, pcDNA3.1
      Hum significantly decreased inflammatory cell counts and eosinophil percentages
      in the BALF, ameliorated lung inflammation, and lowered AHR and IL-4 levels;
      immunization of the mice with pcDNA3.1-Hum reversed humulus-induced reduction of
      serum IFN-gamma and prevented the humulus-triggered reduction of Foxp3(+)Treg
      cell percentage in the spleen. CONCLUSION: We have successfully constructed a
      highly immunogenic pcDNA3.1-Hum DNA vaccine that can mediate immune protection by
      inducing Foxp3(+)Treg cells.

PMID- 24463110
TI  - [Role of NK-22 cells and interleukin-22-related molecules in proliferation of
      fibroblast- like synoviocytes in patients with rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the role of natural killer-22 (NK-22) cells in the
      synovial fluid in the proliferation of fibroblast-like synoviocytes (FLS) in
      patients with rheumatoid arthritis (RA) and explore the possible signal pathway
      involved. METHODS: NK-22 cells in the SF of RA patients were sorted by flow
      cytometry. NK-22 cells were cultured for two weeks and the purity was detected by
      flow cytometry before stimulation with 20 ng/ml phorbol 12-myristate 13-acetate
      and 0.5 umol/L ionomycin for 4 h. The level of interleukin-22 (IL-22) in the
      culture medium supernatant was then measured with ELISA. The proliferation of FLS
      in the presence of the culture supernatant of NK-22 cells was assessed with MTT
      assay at 24, 48 and 72 h, and the effect of IL-22 antibody on FLS proliferation
      was also observed. Real-time PCR and Western blotting were used to detect Stat3
      mRNA and p-Stat3 protein levels, respectively, in the FLS exposed to rhIL-22 and
      AG490. RESULTS: NK-22 cells were successfully sorted by flow cytometry with a
      purity exceeding 90%. The levels of IL-22 in the supernatant of NKp44(+)NK cell
      culture averaged 1273.42?254.48 pg/ml. The FLS proliferated rapidly 24, 48, and
      72 h after the addition of culture supernatant of NK-22 cells (P<0.05). IL-22
      antibody obviously inhibited the proliferation of FLS induced by NK-22 cell
      culture supernatant (P<0.05). Exposure of the FLS to rhIL-22 obviously increased
      cellular Stat3 expression levels, which were significantly lowered by the
      addition of AG490 (P<0.05). CONCLUSION: NK-22 cells in the SF of RA patients can
      produce high concentrations of IL-22 to promote the proliferation of FLS through
      the STAT3 signal pathway.

PMID- 24463111
TI  - [3-bromopyruvate enhances cisplatin sensitivity of hepatocellular carcinoma cells
      in vitro].
AB  - OBJECTIVE: To investigate the effect of 3-bromopyruvate (3-BP) in sensitizing
      hepatocellular carcinoma cells to cisplatin-induced apoptosis and its possible
      mechanism. METHODS: The growth inhibition of HepG2 and SMMC7721 cells following
      exposures to different concentrations of 3-BP and cisplatin was measured by MTT
      assay. The apoptosis of cells treated with 100 umol/L 3-BP with or without 8
      umol/L cisplatin was assessed using flow cytometry with PI staining, and the
      activity of caspase-3 and intracellular ATP level were detected using commercial
      detection kits; the expression of XIAP and PARP was analyzed using Western
      blotting. RESULTS: 3-BP produced obvious inhibitory effects on HepG2 and SMMC7721
      cells at the concentrations of 50-400 umol/L with IC50 values of 238.9?13.9
      umol/L and 278.7?11.7 umol/L for a 48-h treatment, respectively. Cisplatin also
      inhibited the growth of HepG2 and SMMC7721 cells at the concentrations of 2-32
      umol/L, with IC50 values of 16.4?0.9 umol/L and 20.9?1.8 umol/L after a 48-h
      treatment, respectively. Treatment with 100 umol/L 3-BP combined with 8 umol/L
      cisplatin for 48 h resulted in a growth inhibition rate of (60.6?2.2)% in HepG2
      cells and (56.8?2.3)% in SMMC7721 cells, which were significantly higher than
      those in cells treated with 3-BP or cisplatin alone. The combined treatment for
      48 h induced an apoptotic rate of (51.1?4.3)% in HepG2 cells and (46.5?3.9)% in
      SMMC7721 cells, which were also markedly higher than those in cells with 3-BP or
      cisplatin treatment alone. CONCLUSION: 3-BP can sensitize HepG2 and SMMC7721
      cells to cisplatin-induced apoptosis possibly by causing intracellular ATP
      deficiency, down-regulating XIAP, and increasing caspase-3 activity.

PMID- 24463112
TI  - [miR-124a promotes neurite outgrowth by inhibiting iASPP expression].
AB  - OBJECTIVE: To investigate the role of iASPP as the target gene of miR-124a in
      neural development. METHODS: Using the online bioinformatical tool (TargetScan)
      and by reviewing the relevant studies, we selected iASPP as the candidate target
      gene of miR-124a involved in early-stage neuronal differentiation. Luciferase
      reporter assay was used to verify the candidate gene. We transfected M17 cells
      with a miR-124a overexpression plasmid and detected the changes in the protein
      expression of iASPP using Western blotting. With retinoic acid-induced M17 cells
      as the neuronal differentiation model, the role of iASPP in early-stage neuronal
      differentiation was investigated by gene overexpression and gene interference
      techniques. RESULTS: miR-124a inhibited the expression of iASPP in M17 cells by
      interacting with the 3'UTR of iASPP gene. miR-124a promoted neurite outgrowth of
      the cells, which was blocked by iASPP overexpression. CONCLUSION: miR-124a
      promotes neurite outgrowth of M17 cells by inhibiting iASPP expression.

PMID- 24463113
TI  - [Comparison of endoscopic submucosal tunnel dissection with endoscopic submucosal
      dissection for large esophageal superficial neoplasms].
AB  - OBJECTIVE: To compare the safety and efficiency of endoscopic submucosal tunnel
      dissection (ESTD) and endoscopic submucosal dissection (ESD) for large esophageal
      superficial neoplasms. METHODS: A total of 235 consecutive patients undergoing
      endoscopic resection for esophageal neoplasms between October, 2010 and June,
      2013 in our endoscopy center were analyzed retrospectively. According to the
      inclusion and exclusion criteria, 29 patients receiving ESTD or ESD for large
      esophageal superficial neoplasms were enrolled for data analysis. RESULTS: Of the
      29 patients, 11 underwent ESTD and 18 received ESD. The dissection speed of ESTD
      was significantly higher than that of ESD (22.4?5.2 mm(2)/min vs 12.2?4.0
      mm(2)/min, P<0.05). Despite a similar en bloc rate between the two groups (100%
      [11/11] vs 88.9% [16/18], P>0.05), the radical curative rate of ESTD was
      significantly greater than that of ESD (81.8% [9/11] vs 66.7% [12/18], P<0.05).
      No serious bleeding or perforation occurred in the patients except for 1 in ESD
      group with intraoperative bleeding, which was managed with hemostatic forceps.
      Eight patients had postoperative esophageal strictures in relation with
      circumferential extension and the longitudinal length (P<0.05). CONCLUSION: ESTD
      is a safe and effective alternative for large esophageal superficial neoplasms
      with a shortened operative time, a higher dissection speed and a higher radical
      curative rate in comparison with ESD, but postoperative esophageal strictures
      should be closely monitored especially for lesions more than 3/4 of the
      circumferential extension or exceeding 50 mm.

PMID- 24463114
TI  - [Impact of needle size and sonographic feature on accuracy of ultrasound-guided
      breast biopsy].
AB  - OBJECTIVE: To assess the accuracy of ultrasound-guided 16G and 18G core needle
      biopsy for detecting ultrasound visible breast lesions with different sonographic
      features. METHODS: A total of 955 sonographically detected breast lesions
      examined with ultrasound-guided core needle biopsy (US-CNB) and subsequently
      surgically excised from July 2005 to July 2012 were retrospectively reviewed.
      Histological findings of US-CNB and the surgical specimens were analyzed for
      agreements, sensitivities, false negative rates, and underestimate rates
      according to different sonographic features. RESULTS: The pathological results of
      the US-CNB showed malignant lesions in 84.1%, high-risk lesions in 8.4%, and
      benign lesions in 7.5% of the samples. The overall agreement rates were 92.4% for
      16G CNB and 92.8% for 18G CNB; their complete sensitivities and false negative
      rates were both 98.6% and 1.4%, respectively; the high-risk underestimate rates
      and DCIS underestimate rates were 48.0% and 46.2% for 16G CNB vs 53.3% and 41.2%
      for 18G CNB, showing no significant difference between the two groups (P>0.01).
      For both 16G and 18G CNB, the agreements were better for mass lesions than for
      non-mass lesions (P<0.01). For the mass lesions with a diameter no greater than
      10 mm, the agreement rates were lower than the overall data (P<0.01).
      Calcification in the lesions did not affect the agreement rates (P>0.01).
      CONCLUSION: Ultrasound-guided 16G and 18G CNB are both accurate methods for
      evaluating ultrasound visible breast mass lesions with a diameter larger than 10
      mm.

PMID- 24463115
TI  - [Overexpression of Wnt3 inhibits apoptosis of hepatic progenitor cells in vitro].
AB  - OBJECTIVE: To investigate the effects of adenoviral vector-mediated over
      expression of Wnt3 on the apoptosis of hepatic progenitor cells in vitro.
      METHODS: Hepatic progenitor cells transfected with Ad-GFP-Wnt3 vector or the
      control vector Ad-GFP were examined for cell apoptosis under fluorescence
      microscopy with Hoechst 33342 staining, and the proportion of apoptotic cells
      were determined by flow cytometric analysis with Annexin-PE/7-ADD staining. The
      mRNA and protein expressions of Bax, Bcl-2 and Bcl-xl in the cells were detected
      by real-time PCR and Western blotting, respectively. RESULTS: Real-time PCR and
      Western blotting showed a high expression of Wnt3 in Ad-GFP-Wnt3-transfected
      hepatic progenitor cells, which exhibited significantly decreased cell apoptosis
      as compared with the control group. The expressions of Bcl-2 and Bcl-xl mRNA and
      proteins increased significantly while Bax expression decreased obviously in Ad
      GFP-Wnt3-transfected cells (P<0.05). CONCLUSIONS: Adenoviral vector-mediated over
      expression of Wnt3 can suppress apoptosis of hepatic progenitor cells possibly
      through the Bcl-2 pathway.

PMID- 24463116
TI  - [Tumor targeting efficacy of a novel PET radiotracer (1)8F-AlF-NOTA-PRGD2 in
      mice].
AB  - OBJECTIVE: To investigate the tumor targeting efficacy of (18)F-AlF-NOTA-PRGD2, a
      novel radiotracer of Arginine-glycine-aspartic acid (RGD) peptides. METHODS:
      (18)F-AlF-NOTA-PRGD2 was synthesized in one-step by conjugating NOTA-PRGD2 with
      (18)F-AlF at 100 degrees celsius;. The tumor targeting efficacy and in vivo
      biodistribution profile of (18)F-AlF-NOTA-PRGD2, following intravenous injection
      via the tail vein, were evaluated in a nude mouse model bearing subcutaneous
      U87MG glioblastoma xenograft by radioactivity biodistribution assessment, PET/CT
      and microPET/CT. RESULTS: NOTA-PRGD2 was (18)F-fluorinated successfully in one
      step with a yield of 17%-25% within 15-20 min. Radioactivity biodistribution
      study confirmed the tumor-targeting ability of (18)F-AlF-NOTA-PRGD2 in the tumor
      bearing mice. At 1 and 2 h following injection, (18)F-AlF-NOTA-PRGD2 uptake in
      the tumor reached 4.14?1.44 and 2.80?1.18 % ID/g (t=1.910, P=0.070) with
      tumor/brain ratios of 2.95?0.61 and 5.21?2.62, respectively (t=-1.686, P=0.167).
      Both PET/CT and microPET/CT were capable of showing the radioactivity
      biodistribution of (18)F-AlF-NOTA-PRGD2 in the mouse model and clearly displayed
      the tumor, but microPET/CT showed a much better image quality. CONCLUSION: (18)F
      AlF-NOTA-PRGD2 prepared by one-step radiosynthesis can selectively target to the
      tumor, demonstrating its potential as a good radiotracer for tumor imaging.

PMID- 24463117
TI  - [Impact of coronary computed tomography angiography on patient triage
      strategies].
AB  - OBJECTIVE: To investigate the triaging pathways of patients after coronary
      computed tomography angiography (CCTA). METHODS: The patients undergoing CCTA
      were enrolled consecutively during the period from March 3, 2008 to June 23,
      2009. The rate of coronary angiography (CAG) examinations after CCTA was
      calculated. The rates of normal CAG, medication, percutaneous coronary
      intervention (PCI), and coronary artery bypass graft (CABG) were compared between
      CCTA and direct CAG cohorts. RESULTS: A total of 8030 cases receiving CCTA and
      3260 receiving direct CAG were included in the study. The CCTA patients had
      significantly fewer risk factors than those having direct CAG. Of the 8030
      patients undergoing CCTA, 953 (12.03%) received further CAG and 6977 (87.97%) did
      not. Of the patients who received CAG after CCTA, 35 (3.7%) had normal CAG
      findings, 604 (63.4%) underwent PCI, 108 (11.3%) received conservative treatment
      with medications, and 206 (21.6%) underwent CABG. In the 3260 patients directly
      undergoing CAG, 706 (52.3%) underwent subsequent PCI, 142(4.4%) underwent CABG,
      815(25.1%) received medications, and 579 (17.9%) had normal CAG findings.
      Comparison between the cases receiving direct CAG and CAG after CCTA showed that
      CCTA resulted in a significant increase in the revascularization rate (P<0.0001).
      CONCLUSION: CCTA can help prevent unnecessary CAG and allows more accurate
      patient triage.

PMID- 24463118
TI  - [Correlation between endothelin receptor type A gene polymorphism and sporadic
      intracranial aneurysms].
AB  - OBJECTIVE: To investigate the relationship between the 3 polymorphic loci of
      endothelin receptor type A (EDNRA) gene and intracranial aneurysms. METHODS:
      Three EDNRA gene polymorphisms (rs5335, rs6842241, and rs6841581) were genotyped
      using polymerase chain reaction-restriction fragment length polymorphism
      analysis. The genotype and allele frequencies were calculated in the patients and
      the control group to analyze the association between the gene and the size of
      aneurysms. RESULTS: No significant difference was found in the distribution of
      the EDNRA gene genotypes or allele frequencies between the patients and the
      control subjects. Only GG genotype of rs6841581 was found to significantly
      correlate with the size of aneurysms. CONCLUSION: EDNRA gene rs6841581 has
      significant associations with the size of intracranial aneurysms, indicating a
      possible role of EDNRA in the genetic mechanisms of intracranial aneurysms and
      subarachnoid hemorrhage.

PMID- 24463119
TI  - [Renal expression of RANK-RANKL in a rat model of puromycin aminonucleoside
      nephropathy].
AB  - OBJECTIVE: To investigate RANK-RANKL expression in the kidneys of a rat model of
      puromycin aminonucleoside nephropathy (PAN). METHODS: Thirty-six SD rats were
      randomly divided into PAN model group and normal control group. PAN was induced
      by a single intravenous injection of 100 mg/kg puromycin aminonucleoside. Serum
      creatinine and 24-hour urinary protein were measured on days 3, 7, and 14 after
      the injection, and renal pathologies were assessed with optical and immune
      transmission electron microscopy. The expression of RANK and RANKL in the kidneys
      was examined using reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blotting. RESULTS: The PAN model rats showed massive proteinuria and
      elevated serum creatinine on day 3, which peaked on day 7. RANK-RANKL protein and
      mRNA expressions in PAN model group was higher than those in the control group.
      In the PAN rats, RANK was expressed mainly on the top cell membrane and in the
      cytoplasm of renal podocytes with a significantly increased expression level
      compared with that in the control group. CONCLUSION: The PAN rat model shows
      aberrant RANK and RANKL expressions in the podocytes, indicating their
      contribution to podocyte injury in PAN.

PMID- 24463120
TI  - [Establishment of a method for gene complementation in Vibrio parahaemolyticus].
AB  - OBJECTIVE: To establish a method for gene complementation in Vibrio
      parahaemolyticus using the plasmid pBAD33. METHODS: The entire coding region of
      opaR or aphA was amplified by PCR and cloned into pBAD33. The recombinant plasmid
      was transformed into deltaopaR and deltaaphA (the opaR or aphA null mutant
      strain, respectively) separately to construct the complemented mutant strain C
      deltaaphA and C-deltaopaR, respectively. RT-PCR was used to verify the
      transcription of opaR and aphA in the corresponding complemented mutant strains.
      Primer extension experiments were performed to determine the relative mRNA levels
      of mfpA (a gene previously characterized to be negatively regulated by AphA and
      positively by OpaR) in the wild-type strain, deltaopaR, deltaaphA, C-deltaaphA,
      and C-deltaopaR. RESULTS: opaR and aphA were transcribed in the corresponding
      complemented mutant strains, and their mRNA levels were comparable to those
      detected in the wild-type strains. CONCLUSION: A method has been established for
      gene complementation in Vibrio parahaemolyticus using the plasmid pBAD33.

PMID- 24463121
TI  - [Role of exercise in asthma management in children].
AB  - OBJECTIVE: To study the role of exercise in asthma management in children and
      formulate exercise prescriptions for asthmatic children. METHODS: A total of 112
      asthmatic children aged 7-14 years were randomized into control group (n=56, with
      medications only) and exercise group (n=56, with medications and exercise
      prescription) for a trial lasting for 4 months. An asthma diary was used for all
      children to record the morning and evening peak expiratory flow (PEF), daytime
      and nighttime asthma symptom score, use of short-acting beta agonists,
      participation in physical activity, and exercise-induced asthma symptoms.
      RESULTS: Of the 112 children, 5 dropped out before the trial completion. From the
      13th week, PEF variation in exercise group was significantly lowered compared to
      that in the control group (P<0.05). Upon the completion of the trial, the daytime
      and nighttime symptoms score and emergency medication score were all
      significantly lower in the exercise group than in the control group (P<0.05). No
      severe adverse events occurred in the children during the trial. CONCLUSION:
      Exercise for no less than 20 min, 3 days a week for 4 months is safe and
      beneficial for asthma control in children.

PMID- 24463122
TI  - [A mechanical simulation model of the basilar membrane of the cochlea].
AB  - OBJECTIVE: To establish a mechanical simulation model for studying the
      relationship between the characteristic frequency and feature location of the
      basilar membrane of the cochlea. METHODS: Macro-mechanical methods were used to
      simplify the details of the model. With simulation tools, the basilar membrane
      vibration frequency characteristics were analyzed based on the box model.
      RESULTS: The basilar membrane had obvious frequency-selective properties, and the
      basilar membrane from the stapes was sensitive to high frequencies while the
      farther membrane was sensitive to low frequencies. CONCLUSION: The frequency
      characteristics of the basilar membrane of the cochlea is mainly a result of the
      longitudinal variations of the geometric dimensions and material properties and
      is not related with other structures within the cochlea corti.

PMID- 24463123
TI  - [Feasibility of non-contrast enhanced magnetic resonance angiography for
      diagnosis of renal artery stenosis in elderly patients].
AB  - OBJECTIVE: To evaluate the diagnostic efficacy of IFIR-FIESTA technique in
      detecting renal artery stenosis in elderly patients. METHODS: Twenty-seven aged
      patients underwent both IFIR-FIESTA and 3D CE-MRA examinations. The imaging
      quality and renal artery stenosis grades were evaluated. Kappa test was used to
      assess the consistency between the two methods. With CE-MRA as the reference, the
      diagnostic sensitivity, specificity, accuracy, PPV and NPV for IFIR-FIESTA were
      calculated in detecting renal artery stenosis. RESULTS: The images by the two
      methods were 100% qualified for diagnosis, although the image quality of CE-MRA
      was significantly better. IFIR-FIESTA and CE-MRA showed excellent consistency in
      detecting renal artery stenosis. With CE-MRA as the reference, the diagnostic
      sensitivity, specificity, accuracy, PPV and NPV for IFIR-FIESTA were 97.1%, 100%,
      98.1%, 100%, and 95% in detecting renal artery stenosis, respectively.
      CONCLUSION: IFIR-FIESTA is feasible as a routine examination for detecting renal
      artery stenosis in elderly patients.

PMID- 24463124
TI  - [Predictive value of five prognostic models for Budd-Chiari syndrome in China].
AB  - OBJECTIVE: To compare the predictive value of 5 prognostic models (Child-Pugh
      scoring, Clichy prognostic index [PI], New Clichy PI, Rotterdam BCS index, and
      BCS-TIPS PI) for Budd-Chiari syndrome (BCS) in China. METHODS: The clinical data
      of 123 patients with BCS were retrospectively analyzed, among whom 99 survived
      and 24 died. The indices of the 5 prognostic models were respectively calculated,
      and each index was compared by F-test between the survival and death groups. The
      area under curve (AUC), sensitivity, and specificity of the models were computed
      and analyzed by receiver-operator characteristic (ROC) curve. RESULTS: The
      indices of Child-Pugh, Clichy, New Clichy and Rotterdam BCS Index models in the
      death group (8.792?2.0, 5.924?0.783, 5.695?1.81, and 0.615?1.133, respectively)
      were significantly higher than those in the survival group (7.141?1.443,
      5.221?0.834, 3.981?1.033, and -0.148?0.896, respectively, P<0.01), and only BCS
      TIPS model had no significant difference between the two groups (P>0.05). The AUC
      of the 5 indices were 0.738, 0.720, 0.776, 0.721, and 0.502, with Youden indices
      of 0.370, 0.410, 0.439, 0.473, and 0.051, respectively. CONCLUSION: Child-Pugh
      scoring, Clichy PI, New Clichy PI, and Rotterdam BCS Index models can distinguish
      survival from death in BCS patients in China. New Clichy PI has the highest
      predictive value and is suitable for use in China, whereas the other models have
      relatively low predictive values, among which BCS-TIPS model is not advisable.
      Meanwhile effort should be made to establish a prognostic model for BCS in China.

PMID- 24463125
TI  - [Protective effect of adenosine preconditioning against spinal cord ischemia
      reperfusion injury in rats].
AB  - OBJECTIVE: To study the effect of adenosine preconditioning on cell apoptosis and
      expressions of glucose-regulated protein (GRP-78) and cysteinyl aspartate
      specific protease 12 (caspase-12) in rats with spinal cord ischemia-reperfusion
      injury. METHODS: Twenty-seven rats were randomized into 3 equal groups and
      subjected to sham operation (group A), spinal cord ischemia-reperfusion injury
      (group B), or ischemia-reperfusion injury with adenosine treatment. Spinal cord
      ischemia-reperfusion injury was induced by cross-clamping of the abdominal aorta
      inferior to the left renal artery. The spinal cord function was assessed using
      the Modified Tarlov Scale at 6, 12, and 24 h after reperfusion. At 24 h after
      reperfusion, histological analysis was carried out with HE staining; cell
      apoptosis and viability were determined with TUNEL staining, and the expressions
      of GRP-78 and caspase-12 proteins were determined with Western blotting. RESULTS:
      HE staining of the spinal cord showed extensive spinal cord injury such as cell
      edema in group B as compared with group C. Compared with group A, group B showed
      a significantly increased number of apoptotic cells; the number of apoptotic
      cells in group B was greater than that in group C. Compared with group B, group C
      showed significantly increased GRP-78 expression (P<0.01) and decreased caspase
      12 expression (P<0.01). CONCLUSION: Adenosine can up-regulate GRP-78 expression
      and down-regulate caspase-12 expression, and protects the spinal cord against
      ischemia-reperfusion injury by inhibiting cell apoptosis.

PMID- 24463126
TI  - [Effect of different approaches of lentiviral vector transfection on target gene
      expression in rat liver].
AB  - OBJECTIVE: To investigate the optimal approach of lentiviral vector transfection
      for effective delivery of exogenous gene into the liver. METHODS: The lentiviral
      vector was delivered via the ileocolic vein of the ileocecus (portal vein group)
      or via the caudal vein of SD rats. The effect gene transfection into the liver
      was assessed by observing the expression of green fluorescence protein expression
      carried by the lentiviral vector, silencing of LXRalpha mRNA expression mediated
      by RNA interference, and liver transaminase changes. The efficiency and safety of
      the two approaches of transfection were evaluated. RESULTS: All the rats
      receiving lentiviral transfection survived. In the portal vein group, abundant
      green fluorescence was detected in the liver at 96 h following the transfection
      and lasted till 14 days, whereas only weak fluorescence was observed in the
      caudal vein group. The results of RT-PCR demonstrated a significant higher rate
      of LXRalpha knock-down in portal vein group than in caudal vein group
      (0.135?0.002 vs 0.713?0.036, P<0.05). No significant difference in ALT levels
      found between the two groups. CONCLUSIONS: Infusion via the potal vein is
      effective for gene transfection into the liver, and puncture from the ileocolic
      vein of ileocecus can guarantee the survival of rats and improve the transfection
      efficiency without causing liver injury.

PMID- 24463127
TI  - [Effect of low-intensity ultrasound on endothelin-1 and nitrogen monoxide in
      uterine tissues of SD rats following abortion].
AB  - OBJECTIVE: To investigate the effect of low-intensity ultrasound on the contents
      of endothelin (ET-1) and nitrogen monoxide (NO) in uterine tissues of SD rats
      after abortion. METHODS: Thirty female pregnant rats were randomly divided into
      treatment group and control group and received mifepristone and misoprostol to
      induce abortion. The rats in the treatment group were treated by low-intensity
      ultrasound for 30 min/day for 5 consecutive days, and those in the control group
      received sham treatment. The uterine tissue was then taken and homogenized for
      measurement of ET-1 and NO contents using enzyme-linked immunosorbent assay and
      chemical testing. RESULTS: ET-1 content in the uterine tissues was significantly
      higher in the treatment group than in the control group (P<0.05), but NO content
      showed no significant difference between the two groups (P>0.05). CONCLUSIONS:
      Low-intensity ultrasound can promote the contraction of uterine smooth muscles by
      increasing the level of ET-1 to modulate the homeostasis of ET-1 and NO.

PMID- 24463128
TI  - [Effects of exercise of different intensity on early repair of full-thickness
      articular cartilage defects and expressions of MMP-3 and TIMP-1 in rats].
AB  - OBJECTIVE: To evaluate the effects of treadmill running exercise of different
      intensity on early repair of full-thickness defects on the patellofemoral
      articular surface and the changes in the expressions of matrix metalloproteinase
      3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in SD rats.
      METHODS: Twenty-four male SD rats with full-thickness defects on the
      patellofemoral articular surface were randomly assigned into sedentary control
      (SED) group and low-, moderate- and high-intensity running groups (LIR, MIR, and
      HIR groups, respectively). The running groups were trained on treadmill for 6
      consecutive weeks. Blood samples were collected to detect serum MMP-3 and TIMP-1
      levels using ELISA before and after the experiment, and the femoral trochlea were
      collected to assess tissue repair by gross appearance scoring and O Driscoll
      histological scoring with Safranine O-Fast Green staining and Toluidine blue
      staining. RESULTS: In rats in SED group, the defect was filled with hyaline
      articular cartilage-like tissues, as compared to fibrous tissues in LIR and MIR
      groups and subchondral bone damage in HIR group. The SED group scored the highest
      and HIR group the lowest among the 4 groups in gross appearance scoring and O
      Driscoll histological scoring. No significant differences were found in MMP-3 or
      TIMP-1 levels among the groups before training (P>0.05), but after 6 weeks of
      training, serum MMP-3 and TIMP-1 levels differed significantly among the 4 groups
      (P<0.05), and all the 3 running groups had a significantly higher MMP-3 level
      than the control group (P<0.05). After the 6-week training, TIMP-1/MMP-3 ratio
      was significantly higher in SED group than in the 3 running groups, and was the
      lowest in HIR group. CONCLUSION: Both low- and moderate-intensity exercise failed
      to promote resurfacing of full-thickness cartilage defects on the patellofemoral
      articular surface in rats, and high-intensity exercise even induces subchondral
      bone damage. The expression of MMP-3 and TIMP-1 is related to exercise, and the
      TIMP-1/MMP-3 ratio reflects the extent of tissue repair.

PMID- 24463129
TI  - [Effects of farnesoid X receptor agonist on adiponectin and its receptors].
AB  - OBJECTIVE: To investigate the effects of GW4064, a farnesoid X receptor (FXR)
      agonist, on adiponectin and its receptors during the differentiation of 3T3-L1
      preadipocytes and on adiponectin receptors in HepG2 cells. METHODS: The mRNA
      expressions of FXR, PPARgamma2, adiponectin, AdipoR1, and AdipoR2 and the protein
      levels of adiponectin on days 0, 2, 4, 6, and 8 during the differentiation of 3T3
      L1 preadipocytes treated with GW4064 were detected by fluorescent real-time PCR
      and ELISA, respectively. The mRNA expressions of AdipoR1 and AdipoR2 in HepG2
      cells were also examined at 0, 12, 24, and 48 h after GW4064 treatment. RESULTS:
      The mRNA expressions of FXR, PPARgamma2, adiponectin, and AdipoR2 in 3T3-L1
      preadipocytes and AdipoR2 in HepG2 cells treated with GW4064 was significantly
      increased compared with the control group (all P<0.05). The protein level of
      adiponectin was also significantly increased after GW4064 treatment. The
      expression of AdipoR1 in either 3T3-L1 preadipocytes or HepG2 cells showed no
      significant changes after GW4064 treatment. CONCLUSION: GW4064 can up-regulate
      the expressions of FXR, PPARgamma2, adiponectin, AdipoR2 in 3T3-L1 preadipocytes
      and AdipoR2 in HepG2 cells. As adiponectin and its receptors are two important
      factors in the treatment of non-alcoholic fatty liver disease, FXR agonist may
      potentially produce therapeutic effect on non-alcoholic fatty liver disease and
      can regulate adipocytes via up-regulating PPARgamma during adipocyte
      differentiation.

PMID- 24463130
TI  - [Prevalence and risk factors of postpartum depression in Tianhe District of
      Guangzhou].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of postpartum
      depression (PPD) in Tianhe district of Guangzhou. METHODS: A total of 1428
      postpartum women in 3 hospitals in Tianhe District of Guangzhou were screened
      with Edinburg Postnatal Depression Scale (EPDS), Social Support Rating Scale
      (SSRS) and a self-designed questionnaire of PPD-related factors during the period
      from May to September, 2013. RESULTS: The prevalence of PPD was 20.03% in these
      women. Unconditional logistic regression analysis showed a significant
      correlation of PPD with education, delivery mode, only daughter, relationship
      between mother-in-law and daughter-in-law, newborn gender satisfaction and
      housing condition (P<0.05). Multivariate logistic regression analysis identified
      education, delivery mode, only daughter, relationship between mother-in-law and
      daughter-in-law, and newborn gender satisfaction as the risk factors for PPD, and
      housing condition was negatively correlated with the incidence of PPD with an OR
      value of 0.900. Compared with healthy postpartum women, the patients with PPD
      exhibited significantly reduced total score of social support rating scale, score
      of objective support, score of subjective support, and social utilization degree.
      CONCLUSION: The prevalence of PPD is high in Tianhe District of Guangzhou, and
      health education and psychosocial intervention should be offered to prevent PPD.

PMID- 24463131
TI  - [Effect of ulinastatin for perioperative cardiac protection in elderly patients
      undergoing major gastrointestinal surgery].
AB  - OBJECTIVE: To study protective effect of ulinastatin on perioperative cardiac
      function in elderly patients undergoing major gastrointestinal surgery. METHODS:
      Sixty elderly patients (32 male and 28 female patients) aged 60-82 years
      scheduled for major gastrointestinal surgery were randomized into ulinastatin
      group and control group. The patients in ulinastatin group received 2*10(5) U
      ulinastatin rapidly administered via a intravenous pump immediately before
      operation with subsequent continuous infusion at the rate of 1*10(5) U until the
      completion of surgery, and those in the control group received the same amount of
      saline instead. In both groups, the mean arterial pressure (MAP), heart rate
      (HR), left ventricular ejection fraction (LVEF), and cardiac output (CO) were
      monitored immediately before surgery (T0) and at 1 h (T1), 2 h (T2) and 3 h (T3)
      after the start of surgery. The total dopamine dose used was recorded at the end
      of surgery, and blood samples were collected at T0 and at 6 h (T4) and 12 h (T5)
      after the operation for determination of serum levels of cTn, CK-MB and BNP.
      RESULTS: In both groups, MAP, LVEF and CO were significantly decreased at T2 and
      T3 (P<0.05) and serum levels of cTn, CK-MB and BNP significantly increased at T4
      and T5 compared to those at T0 (P<0.05). Compared with the control group, the
      patients in ulinastatin group showed significantly higher MAP, LVEF and CO at T2
      and T3 and lower serum levels of cTn, CK-MB and BNP at T4 and T5. CONCLUSION:
      Ulinastatin offers effective perioerative cardiac protection in elderly patients
      undergoing major gastrointestinal surgery.

PMID- 24463132
TI  - [Correlation between Pet-CO2 and PaCO2 in morbidly obese patients during
      anesthesia for laparoscopic gastric bypass surgery].
AB  - OBJECTIVE: To investigate the correlation between arterial partial pressure of
      CO2 (PaCO2) and end expiratory tidal partial pressure of CO2 (Pet-CO2) in
      morbidly obese patients during anesthesia for laparoscopic gastric bypass
      surgery. METHODS: Forty morbidly obese patients with a body mass index (BMI)
      between 35 and 50 kg/m(2) underwent laparoscopic gastric bypass surgery under
      general anesthesia. PaCO2 and Pet-CO2 were measured after intubation and before
      induction of pneumoperitoneum (T0), at 30 min (T1), 60 min (T2), and 120 min (T3)
      during pneumoperitoneum, and at 30 min (T4) and 60 min (T5) after deflation.
      RESULTS: At each time point of measurement, Pet-CO2 was lower than PaCO2 in all
      the patients. PaCO2 and Pet-CO2 were positively correlated before, during, and
      after pneumoperitoneum (P<0.05). At a moderate pressure of CO2 pneumoperitoneum
      (16 mmHg), the level of correlation between PaCO2 and Pet-CO2 at T1, T2, and T3
      differed from that before and after post-pneumoperitoneum. CONCLUSIONS: PaCO2 and
      Pet-CO2 are closely correlated during a moderate CO2 pneumoperitoneum in morbidly
      obese patients undergoing laparoscopic gastric bypass surgery.

PMID- 24463133
TI  - [Effects of moxibustion at Shenque (CV8) on gastrointestinal function in rats
      undergoing gastric perforation repair].
AB  - OBJECTIVE: To assess the effects of moxibustion at Shenque (CV8) in promoting
      gastrointestinal function recovery in rats following gastric perforation repair
      and explore the underlying mechanism. METHODS: Thirty male SD rats with glacial
      acetic acid-induced gastric perforation underwent surgical repair of the
      perforation. The rats were then randomized 8 days later into model group (n=10),
      domperidone group (n=10), and moxibustion group(n=10) and treated with
      physiologic saline, domperidone suspension, and moxibustion at Shenque (CV8),
      respectively. Gastric antral myoelectric activities of the rats were observed and
      peripheral blood levels of TNF-alpha, IL-6, and T lymphocyte subpopulation were
      determined. RESULTS: Gastric antral myoelectric activities in rats receiving
      moxibustion were stronger than those in the model group (P<0.05) but comparable
      with those in domperidone group (P>0.05). TNF-alpha and IL-6 level were decreased
      significantly and T lymphocyte subpopulations increased significantly in
      moxibustion group compared with those in the model and domperidone groups
      (P<0.05). CONCLUSION: Moxibustion at Shenque (CV8) can promote the recovery of
      gastrointestinal functions in rats undergoing gastric perforation repair possibly
      by enhancing gastrointestinal electric activity, suppressing inflammation, and
      improving the cellular immune function, and can therefore serve as a simple and
      effective adjuvant therapy during the perioperative period.

PMID- 24463134
TI  - [Pro-apoptosis and selective anticancer activities of prostate apoptosis response
      protein 4: research progress and prospects].
AB  - OBJECTIVE: As a pro-apoptotic factor, prostate apoptosis response protein 4 (par
      4) was first found in the male hormone-dependent prostate cells (AT-3).
      Endogenous Par-4 sensitizes cancer cells to apoptotic stimuli, but exogenous Par
      4 selectively induces apoptosis in cancer cells, and these activities depends on
      the structure of its core domain SAC. Par-4 and SAC can specifically induce
      apoptosis of cancer cells but not of normal cells, and are therefore potential
      anti-cancer drugs. In this review we summarize the discovery, structure, and
      function of par-4, and its intracellular signaling pathways, then discuss the
      application prospects of Par-4 and SAC in the clinical treatment of cancer and
      the problems in its research and clinical applications.

PMID- 24463135
TI  - [Therapeutic effect of sorafenib on portal hypertension: research progress and
      mechanisms].
AB  - OBJECTIVE: Portal hypertension, as one of the major complications of liver
      cirrhosis, is a common clinical syndrome characterized by an increased portal
      pressure and the formation of portal-systemic collaterals. Currently no ideal
      therapeutic agent has been available for portal hypertension. Sorafenib is an
      oral tyrosine kinase inhibitor that has been shown to significantly improve blood
      flow dynamics, inhibit angiogenesis, reduce liver fibrosis and decrease portal
      pressure in the treatment of portal hypertension. The authors review the progress
      in the research of sorafenib in the treatment of portal hypertension and the
      mechanisms of its actions.

PMID- 24463136
TI  - [Fluid resuscitation in a patient with severe hypovolemic shock and severe
      pulmonary capillary leak].
AB  - OBJECTIVE: A male patient undergoing extracorporeal ultrasound lithotripsy
      developed the symptoms of dyspnea, low blood pressure, palpitations, chest
      tightness, and sweating, and a clinical diagnosis of pulmonary capillary leak and
      hypovolemic shock was made. Pulse indicator continuous cardiac output (PiCCO)
      technique was used for resuscitation according to the measurements of
      extravascular lung water index (EVLWI) and global end-diastolic volume index
      (GEDI). The patient showed low levels of cardiac output (CO) and GEDI with a peak
      EVLWI of 32 ml/kg and profuse pink and thin sputum overflow from the trachea. The
      high ventilator support parameters failed to correct low oxygen saturation.
      Restricted fluid infusion was used to reduce pulmonary edema. Colloidal solution
      was given when GEDI was below 500 ml/m(2), and the volume and fluid infusion rate
      were reduced for a GEDI higher than 500 ml/m(2). Pulmonary edema was gradually
      reduced after the treatments with improvement of lactic acid level and liver and
      kidney functions. Vasopressors were withdrawn 6 days later, mechanical
      ventilation was discontinued 10 days later, and tracheal intubation was removed
      25 days later, after which the patient was discharged. In the treatment of the
      patient, PiCCO monitoring played an important role.

PMID- 24463137
TI  - [Changes in serum pepsinogen in patients with liver cirrhosis and portal
      hypertensive gastropathy].
AB  - OBJECTIVE: To determine serum pepsinogen levels in patients with liver cirrhosis
      and investigate the functions of the gastric mucosa in these patients with
      concurrent portal hypertensive gastropathy (PHG). METHODS: Fifty-one patients
      with liver cirrhosis and 22 healthy controls were studied by gastroscopy. The
      hepatic function of the patients with or without PHG were evaluated with Child
      Pugh grade. Helicobacter pylori infection was detected using rapid urease test or
      exhalation of carbon 13. The serum pepsinogen I and II levels were tested by
      latex-enhanced immunoturbidimetry to calculate the PGI/PGII ratio (PGR). RESULTS:
      In cirrhotic patients, the levels of serum PGI and PGR were lower than those in
      the healthy controls. The patients without PHG had a serum PGI level of
      49.48+23.86 ug/L, significantly lower than that in PHG patients (74.85+30.27
      ug/L, P=0.000). The levels of serum PG II in patients with H.pylori infection was
      significantly higher that in patients free of H.pylori infection (P=0.003).
      CONCLUSION: The serum level of PGI decreases obviously in patients with hepatic
      cirrhosis and PHG, who can have damages of the gastric mucosa lamina propria and
      reduced secretory function of the gastric mucosa. H.pylori infection may affect
      the level of PGII. There is no significant correlation between serum PG level and
      liver function, but to a certain extent, serum PG level especially PGI can
      reflect the function of gastric mucosa in patients of liver cirrhosis.

PMID- 24463138
TI  - [Prevalence of syphilis during pregnancy and risk factors for maternal and
      perinatal infections: a 2009-2013 survey].
AB  - OBJECTIVE: To analyze the risk factors for maternal and perinatal syphilis
      infections in Guangzhou. METHODS: We collected the data of pregnant women with
      perinatal syphilis infections from the Obstetrics Critical Care Center, Third
      Affiliated Hospital of Guangzhou Medical University during the period from
      January, 2009 to April, 2013. RESULTS: in the 64 253 pregnant women surveyed, the
      mean annual incidence of syphilis during pregnancy was 0.255% within the surveyed
      period. In women with syphilis during pregnancy, those receiving normal anti
      syphilis treatment had a significantly lower rate of neonatal serological
      syphilis positivity and those without treatment (55.81% vs 100%); the serological
      syphilis positivity rates differed significantly between neonates with parental
      syphilis infection and those without (54.348% vs 20%). Of the women with syphilis
      during pregnancy, 82.14% reported syphilis of the spouse, 80.36% were floating
      population, and 78.57% had previous multiple pregnancies. CONCLUSION: The
      incidence of syphilis during pregnancy shows a linear growth in the 5 past years
      in Guangzhou. Maternal syphilis during pregnancy without proper anti-syphilis
      treatment and vertical transmission are the most important risk factors for
      neonatal syphilis. A syphilis spouse, floating population, and multiple
      pregnancies all contribute to neonatal syphilis.

PMID- 24463140
TI  - Managing genetic tests, surveillance, and preventive medicine under a public
      health insurance system.
AB  - There is a prospect in the medium to long term future of substantial advancements
      in the understanding of the relationship between disease and genetics. We
      consider the implications of increased information from genetic tests about
      predisposition to diseases from the perspective of managing health care provision
      under a public health insurance scheme. In particular, we consider how such
      information may potentially improve the targeting of medical surveillance (or
      prevention) activities to improve the chances of early detection of disease
      onset. We show that the moral hazard implications inherent in surveillance and
      prevention decisions that are chosen to be privately rather than socially optimal
      may be exacerbated by increased information about person-specific predisposition
      to disease. 

PMID- 24463139
TI  - Dkk2/Frzb in the dermal papillae regulates feather regeneration.
AB  - Avian feathers have robust growth and regeneration capability. To evaluate the
      contribution of signaling molecules and pathways in these processes, we profiled
      gene expression in the feather follicle using an absolute quantification
      approach. We identified hundreds of genes that mark specific components of the
      feather follicle: the dermal papillae (DP) which controls feather regeneration
      and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and
      nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a
      feather starts to branch. The feather DP is enriched in BMP/TGF-beta signaling
      molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are
      mainly expressed in the feather epithelium and pulp. We find that while Wnt
      signaling is required for the maintenance of DP marker gene expression and
      feather regeneration, excessive Wnt signaling delays regeneration and reduces
      pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated
      overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual
      feather axes formation. Our results suggest that the Wnt signaling in the
      proximal feather follicle is fine-tuned to accommodate feather regeneration and
      axis formation. 

PMID- 24463141
TI  - The effects of health information technology on the costs and quality of medical
      care.
AB  - Information technology has been linked to productivity growth in a wide variety
      of sectors, and health information technology (HIT) is a leading example of an
      innovation with the potential to transform industry-wide productivity. This paper
      analyzes the impact of health information technology (HIT) on the quality and
      intensity of medical care. Using Medicare claims data from 1998 to 2005, I
      estimate the effects of early investment in HIT by exploiting variation in
      hospitals' adoption statuses over time, analyzing 2.5 million inpatient
      admissions across 3900 hospitals. HIT is associated with a 1.3% increase in
      billed charges (p-value: 5.6%), and there is no evidence of cost savings even
      five years after adoption. Additionally, HIT adoption appears to have little
      impact on the quality of care, measured by patient mortality, adverse drug
      events, and readmission rates. 

PMID- 24463142
TI  - Competition and the impact of online hospital report cards.
AB  - Information on the quality of healthcare gives providers an incentive to improve
      care, and this incentive should be stronger in more competitive markets. We
      examine this hypothesis by studying Pennsylvanian hospitals during the years 1995
      2004 to see whether those hospitals located in more competitive markets increased
      the quality of the care provided to Medicare patients after report cards rating
      the quality of their Coronary Artery Bypass Graft programs went online in 1998.
      We find that after the report cards went online, hospitals in more competitive
      markets used more resources per patient, and achieved lower mortality among more
      severely ill patients. 

PMID- 24463143
TI  - Outcome of gastro-oesophageal reflux-related respiratory manifestations after
      laparoscopic fundoplication.
AB  - AIMS: Patients with refractory respiratory symptoms related to gastro-oesophageal
      reflux disease (GORD) such as asthma and cough are being referred for
      laparoscopic fundoplication (LFP), as recommended by the Society of American
      Gastrointestinal and Endoscopic Surgeons (SAGES). However there are limited data
      regarding symptomatic response to fundoplication in this group of patients.
      METHOD: A 7 year retrospective review was performed to study the efficacy of LFP
      in the treatment of patients with respiratory manifestations of GORD. Patients
      were followed up from 4 to 6 weeks (short-term) to 6-12 months (long-term) post
      operatively. RESULTS: Of 208 patients who underwent LFP, 73 (35%) patients were
      eligible for inclusion into the study. 55 (75%) patients had improved respiratory
      symptoms at short-term follow-up. At long-term follow-up, 7 of these patients had
      recurrence of respiratory symptoms, while 4 patients had improvement not
      initially apparent. No significant predictive factor for the success or failure
      of surgery was identified. 190 (91%) of 208 patients had symptomatic improvement
      in GORD at short-term follow-up. CONCLUSION: LFP is effective with the response
      rates over 75% in the control of respiratory manifestation of GORD, compared to
      over 91% response rate in the control GOR symptoms alone. More research is needed
      to identify factors to aid patient selection to improve response rate.

PMID- 24463144
TI  - Double-stapling technique for transhiatal distal esophageal resection:
      feasibility test in a cadaver model.
AB  - OBJECTIVES: To assess the feasibility of a new surgical technique for the
      resection of the distal third of the esophagus and/or cardias for neoplasm.
      METHODS: This surgical technique consists of two steps: For this purpose we built
      a stainless steel support bar for the anvil that is thinner than the freespace of
      a standard linear suturing stapler (TATM). The support bar holds up a push rod
      that can be adapted to the hooking-unhooking of the anvil. RESULTS: We performed
      our new technique on five cadavers. We did not encounter any difficulty during
      the procedures. We tested the anastomosis with hydropneumatic assessment without
      recording any leaks. The esophago-enteric anastomosis was then opened without
      finding any mechanical defects related to the procedure. CONCLUSION: It can often
      be very difficult to fashion a safe hand-sewn pouch or a purse string around the
      anvil of an EEATM during the resection of the distal third of the esophagus or
      the cardias by a trans-hiatal approach. Moreover, there is no standardized
      procedure to minimize anastomotic leak. To avoid these mechanical problems we
      designed this innovative procedure, which is considered to be reproducible
      without significant training.

PMID- 24463146
TI  - A Novel Presenilin 1 Mutation in Early-Onset Alzheimer's Disease With Prominent
      Frontal Features.
AB  - Familial Alzheimer's disease (AD) is a rare disorder involving known autosomal
      dominant mutations in the amyloid precursor protein and presenilin (PSEN) 1 and
      2. Here, we present a case of early-onset AD with prominent frontal features
      associated with a novel deletion of codon 40 in the PSEN1 gene. Serial brain
      magnetic resonance imaging and(18)F florbetapir imaging show prominent
      involvement of the frontal lobes, corresponding with the clinical presentation.
      This case report illustrates a possible link between a novel PSEN1 mutation and
      frontal variant AD.

PMID- 24463145
TI  - Splicing factor 3B1 hypomethylation is associated with altered SF3B1 transcript
      expression in older humans.
AB  - Ageing in man is associated with changes to the splicing factor pool. A
      proportion of splicing factors are regulated during ageing by mechanisms
      involving the Ataxia Telangiectasia Mutated (ATM) gene, but the factors that
      determine the remaining proportion have yet to be identified. DNA methylation is
      known to be an important regulatory mechanism of gene expression. We assessed age
      associated methylation and expression levels for 27 splicing factor genes, in
      peripheral blood samples from the InCHIANTI study. Examination of splicing
      patterns at specific loci was examined in a second cohort, the Exeter 10000
      study. 27/502 methylation probes in 17 different genes were associated with age.
      Most changes were not associated with transcript expression levels or splicing
      patterns, but hypomethylation of the SF3B1 promoter region was found to mediate
      53% of the relationship between age and transcript expression at this locus
      (p=0.02). DNA methylation does not appear to play a major role in regulation of
      the splicing factors, but changes in SF3B1 expression may be attributable to
      promoter hypomethylation at this locus. SF3B1 encodes a critical component of the
      U2 snRNP; altered expression of this gene may therefore contribute to the loss of
      regulated mRNA splicing that occurs with age. 

PMID- 24463147
TI  - Study on multilayer structures prepared from heparin and semi-synthetic cellulose
      sulfates as polyanions and their influence on cellular response.
AB  - Multilayer coatings of polycationic chitosan paired with polyanionic semi
      synthetic cellulose sulfates or heparin were prepared by the layer-by-layer
      method. Two different cellulose sulfates (CS) with high (CS2.6) and intermediate
      (CS1.6) sulfation degree were prepared by sulfation of cellulose. Multilayers
      were fabricated at pH 4 and the resulting films were characterized by several
      methods. The multilayer 'optical' mass, measured by surface plasmon resonance,
      showed little differences in the total mass adsorbed irrespective of which
      polyanion was used. In contrast, 'acoustic' mass, calculated from quartz crystal
      micro balance with dissipation monitoring, showed the lowest mass and dissipation
      values for CS2.6 (highest sulfation degree) multilayers indicating formation of
      stiffer layers compared to heparin and CS1.6 layers which led to higher mass and
      dissipation values. Water contact angle and zeta potential measurements indicated
      formation of more distinct layers with using heparin as polyanion, while use of
      CS1.6 and CS2.6 resulted into more fuzzy intermingled multilayers. CS1.6
      multilayers significantly supported adhesion and growth of C2C12 cells where as
      only few cells attached and started to spread initially on CS2.6 layers but
      favoured long term cell growth. Contrastingly cells adhered and grew poorly on to
      the layers of heparin. This present study shows that cellulose sulfates are
      attractive candidates for multilayer formation as potential substratum for
      controlled cell adhesion. Since a peculiar interaction of cellulose sulfates with
      growth factors was found during previous studies, immobilization of cellulose
      sulfate in multilayer systems might be of great interest for tissue engineering
      applications.

PMID- 24463148
TI  - Effects of cholesterol incorporation on the physicochemical, colloidal, and
      biological characteristics of pH-sensitive AB2 miktoarm polymer-based
      polymersomes.
AB  - In our previous study, a histidine-based AB2 miktoarm polymer, methoxy
      poly(ethylene glycol)-b-poly(l-histidine)2 (mPEG-b-(PolyHis)2), was designed to
      construct pH-sensitive polymersomes that transform in acidic pH; the polymer self
      assembles into a structure that mimics phospholipids. In this study, the
      polymersomes further imitated liposomes due to the incorporation of cholesterol
      (CL). The hydrodynamic radii of the polymersomes increased with increasing CLwt%
      (e.g., 70 nm for 0 wt% vs. 91 nm for 1 wt%), resulting in an increased capacity
      for encapsulating hydrophilic drugs (e.g., 0.92 MUL/mg for 0 wt% vs. 1.42 MUL/mg
      for 1 wt%). The CL incorporation enhanced the colloidal stability of the
      polymersomes in the presence of serum protein and retarded their payload release.
      However, CL-incorporating polymersomes still demonstrated accelerated release of
      a hydrophilic dye (e.g., 5(6)-carboxyfluorescein (CF)) below pH 6.8 without
      losing their desirable pH sensitivity. CF-loaded CL-incorporating polymersomes
      showed better cellular internalization than the hydrophilic CF, whereas
      doxorubicin (DOX)-loaded CL-incorporating polymersomes presented similar or
      somewhat lower anti-tumor effects than free hydrophobic DOX. The findings suggest
      that CL-incorporating mPEG-b-(PolyHis)2-based polymersomes may have potential for
      intracellular drug delivery of chemical drugs due to their improved colloidal
      stability, lower drug loss during circulation, acidic pH-induced drug release,
      and endosomal disruption.

PMID- 24463149
TI  - Letrozole dispersed on poly (vinyl alcohol) anchored maleic anhydride grafted low
      density polyethylene: a controlled drug delivery system for treatment of breast
      cancer.
AB  - The present work focuses on the design of a drug delivery system for systemic,
      controlled release of the poorly soluble breast cancer drug, letrozole. The drug
      delivery system was prepared in two steps: a low density polyethylene (LDPE)
      substrate surface was grafted with maleic anhydride (MA) via solution grafting
      technique. Next, the grafted substrate was used to anchor a hydrophilic polymeric
      drug release system consisting of poly (vinyl alcohol) (PVA). The PVA anchored MA
      grafted LDPE (PVA/MA-g-LDPE) drug release system was used for the controlled
      release of letrozole. This system was characterized using ATR-FTIR
      spectrophotometry, surface profilometry, and scanning electron microscopy.
      Biocompatibility studies were also carried out. In vitro release studies of
      letrozole from the system were performed in distilled water and phosphate buffer
      saline (PBS) at 37 degrees C. Release of ~90% letrozole from hydrophilic PVA
      matrix was observed within a period of 35 days. A high correlation coefficient
      (R(2)=0.99) was seen between the release of letrozole in distilled water and PBS.
      Cytotoxicity studies using MTT colorimetric assay suggested that all samples were
      biocompatible. It is concluded that the letrozole delivery system appears to
      overcome the limitations associated with letrozole by providing enhanced drug
      dissolution rate, controlled release and improved bioavailability of the
      incorporated drug and, therefore, seems to have extended therapeutic effects.

PMID- 24463150
TI  - Miscibility and interactions of animal and plant sterols with choline plasmalogen
      in binary and multicomponent model systems.
AB  - In this work miscibility and interactions of sterols with choline plasmalogen (PC
      plasm) in Langmuir monolayers were studied. Moreover, the properties of
      cholesterol/phosphatidylcholine/plasmalogen mixtures of different PC-plasm
      concentration were investigated. The foregoing systems were treated as a model of
      cancer cell membranes, which are of higher plasmalogen level than normal cells.
      Finally, the influence of beta-sitosterol and stigmasterol (phytosterols
      differing in anticancer potency) on these mixtures was verified. The properties
      of monolayers were analyzed based on the parameters derived from the surface
      pressure-area isotherms and images taken with Brewster Angle Microscope. It was
      found that at 30% of sterol in sterol/plasmalogen monolayer the lipids are
      immiscible and 3D crystallites are formed within the film. Cholesterol molecules
      mix favorably with PC-plasm at Xchol >= 0.5, while the investigated phytosterols
      only at their prevailing proportion in binary system. The increase of choline
      plasmalogen in cholesterol/phosphatidylcholine monolayer causes destabilization
      of the system. Moreover, the incorporation of phytosterols into
      cholesterol/phosphatidylcholine+PC-plasm mixtures disturbed membrane morphology
      and this effect was stronger for beta-sitosterol as compared to stigmasterol. It
      was concluded that the presence of vinyl ether bond at sn-1 position in PC-plasm
      molecule strongly affects miscibility of choline plasmalogen with sterols. The
      comparison of the collected data with those reported in literature allowed one to
      conclude that miscibility and interactions of sterols with PC-plasm are less
      favorable than those with phosphatidylcholine. It was also suggested that
      overexpression of plasmalogens in cancer cell membranes may be a factor
      differentiating sensitivity of cells to anticancer effect of phytosterols.

PMID- 24463151
TI  - Label-free detection of viruses on a polymeric surface using liquid crystals.
AB  - In this study, we demonstrated a label-free detection of viruses using liquid
      crystals (LCs) on a polymeric surface with periodic nanostructures. The polymeric
      nanostructures, which hold sinusoidal anisotropic patterns, were created by a
      sequential process of poly-(dimethylsiloxane) buckling and replication of the
      patterns on a poly-(urethane acrylate) surface containing a film of gold. After
      immobilization of human cytomegalovirus- and adenovirus-antibodies onto the
      polymeric surface treated with a mixed self-assembled monolayer, a uniform
      appearance reflecting the uniform orientation of 4-cyano-4'-pentylbiphenyl (5CB)
      was observed. Conversely, binding of viruses to their antibody decorated surface
      induced a random appearance of 5CB from the random orientation of 5CB. The
      uniform to random orientational transition of 5CB indicates that the anisotropic
      topography of the polymeric surface was masked after specific binding of viruses
      to the antibody decorated surface. We evaluated the specificity of the binding
      events by confirming topographical changes and optical thickness using atomic
      force microscopy and ellipsometry, respectively. These results demonstrate that
      polymeric surfaces with continuous anisotropic patterns can be used to amplify
      the presence of nanoscopic virions into an optical response of LC, as well as
      expand the scope of LC-based biological detection on polymeric solid surfaces. 

PMID- 24463152
TI  - Innovative microRNA purification based on surface properties modulation.
AB  - The increasing interest in circulating microRNAs (miRNAs) as potential non
      invasive cancer biomarkers has prompted the rapid development of several
      extraction techniques. However, current methods lack standardization and are
      costly and labor intensive. In light of this, we developed a microRNA solid-phase
      extraction strategy based on charge and roughness modulation on substrate
      surfaces. PECVD treated silicon oxide (PECVD-SO) and thermally grown silicon
      oxide (TG-SO) surfaces were functionalized with positively charged 3
      aminopropyltriethoxysilanes (APTES) and neutral poly(ethylene glycol) silanes
      (PEG-s) mixed in different proportions to modulate the density of net positive
      charges and the roughness of the substrate. Characterization of the surfaces was
      performed by atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS) and s-SDTB (sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate) assay in
      order to investigate the surface morphology and chemical composition,
      respectively. Adsorption and elution efficiency were assessed by fluorescence
      microscopy by means of synthetic fluorescently labeled microRNAs. We identified
      PECVD-SO functionalized with 0.1% APTES and 0.9% 21-24 units long PEG-s as a
      promising surface able to selectively bind microRNAs and release them in the
      presence of a basic buffer (pH=9) compatible with downstream analyses. MicroRNA
      integrity was assessed by reverse transcription and real-time PCR and confirmed
      by electrophoresis (Agilent 2100 Bioanalyzer), while binding competition from
      circulating DNA and proteins was excluded by fluorescence analyses and real-time
      PCR. On the contrary, total RNA slightly decreased miRNA adsorption. In
      conclusion, we showed an innovative and easy solid-state purification method for
      circulating miRNAs based on charge interaction, which could pave the path to
      future diagnostic and prognostic assays feasible as a routine test.

PMID- 24463153
TI  - Development and characterization of two nano-structured systems for topical
      application of flavanones isolated from Eysenhardtia platycarpa.
AB  - Many of the inflammatory diseases are becoming common in ageing society
      throughout the world. The clinically used anti-inflammatory drugs suffer from the
      disadvantage of side effects. Alternative to these drugs are natural products,
      since ancient times traditional medicines are being used for the treatment of
      inflammation. In the present study, four flavanones isolated from Eysenhardtia
      platycarpa leaves with a potent pharmacological activity were formulated in
      effective drug delivery systems: nanoemulsion and polymeric nanoparticles for
      topical use as novel anti-inflammatory topical formulations. Nanoemulsion system
      exhibited droplet sizes less than 70 nm and polymeric nanoparticles with a size
      of 156-202 nm possessed zeta potential values less than -25 mV that provided good
      stability and obtained high entrapment efficiency (78-90%). In vitro release and
      ex vivo permeation studies were performed on Franz-type diffusion cells and
      quantified by high performance liquid chromatography (HPLC), all formulations
      showed steady state release profiles over time and steady increase of flavanones
      in the skin permeation test. The anti-inflammatory activity, tested by TPA (12-O
      tetradecanoylphorbol-13-acetate), induced oedema in mice ear suggesting that
      prenylated flavanones improve significantly their anti-inflammatory activity when
      are vehiculized in nanosized systems. Our results suggested that 5-hydroxy-7
      methoxy-6-prenyl flavanone loaded nanoemulsion and polymeric nanoparticle could
      be proposed as potential topical anti-inflammatory formulations with the best
      properties for the treatment of inflammatory disorders.

PMID- 24463155
TI  - Effect of quince seed mucilage edible films incorporated with oregano or thyme
      essential oil on shelf life extension of refrigerated rainbow trout fillets.
AB  - The effects of quince seed mucilage film (QSMF) containing oregano (O) or thyme
      (T) essential oil on shelf life extension of rainbow trout (Oncorhynchus mykiss)
      fillets during refrigerated storage (4 degrees C) were evaluated over a period of
      18days. Films were prepared in four different concentrations of essential oils,
      including 0, 1, 1.5 and 2%. The control and the wrapped fillet samples were
      analyzed periodically for microbiological (aerobic and psychrotrophic count,
      Pseudomonas spp., H2S-producing bacteria, lactic acid bacteria, and
      Enterobacteriaceae), chemical (TBA, TVB-N, TMA-N), and sensory characteristics.
      Bacteria grew most quickly in trout fillets stored in air, followed by those
      wrapped with QSMF and the lowest counts were in wrapped samples with QSMF+2%T.
      Pseudomonas spp., Enterobacteriaceae and LAB counts were significantly lower in
      samples wrapped with QSMF+2%T. The lowest TBA value was obtained in fillets
      wrapped QSMF containing 2% oregano essential oil. The strong antioxidant activity
      of QSMF+2%O was related to the composition of oregano essential oil. The GC
      analysis of essential oil components revealed that carvacrol (81.85%) was the
      major component of oregano essential oil. TBA value varied for all treatments and
      remained lower than 2mg MDA/kg throughout storage. The formation of TVB-N, TMA-N
      increased with time of storage. TVB-N and TMA-N correlated well with the
      microbiological data, indicating that along with TVB-N, TMA-N may serve as a
      useful index for fillets spoilage. QSMF extended the microbial shelf life of
      rainbow trout fillets by 2days, whereas the QSMF+1%O, QSMF+1.5%O, QSMF+2%O,
      QSMF+1%T, QSMF+1.5%T and QSMF+2%T resulted in a significant shelf life extension
      of the trout fillets by 3, 5, 9, 6, 10 and 11days, respectively, as compared to
      the control samples. 

PMID- 24463156
TI  - Microbial biodiversity in cheese consortia and comparative Listeria growth on
      surfaces of uncooked pressed cheeses.
AB  - The study set out to determine how changes in the microbial diversity of a
      complex antilisterial consortium from the surface of St-Nectaire cheese modify
      its antilisterial activities. On the basis of the microbial composition of a
      natural complex consortium named TR15 (Truefood consortium 15), three new
      consortia of different species and strain compositions were defined: TR15-SC (58
      isolates from TR15 collection), TR15-M (pools of isolates from selective counting
      media) and TR15-BHI (pools of isolates from BHI medium). Their antilisterial
      activities on the surfaces of uncooked pressed cheese made with pasteurised milk
      were compared with the activity of complex consortium TR15 and a control cheese
      inoculated only with starter culture (Streptococcus thermophilus, Lactobacillus
      delbrueckii). The natural consortium TR15 was the most inhibitory, followed by
      reconstituted consortium TR15-BHI. The dynamics of the cheese rind microbial
      flora were monitored by counting on media and by isolate identification using 16S
      rDNA sequencing and direct 16S rDNA Single Strand Conformation Polymorphism
      analysis. The combination of these methods showed that rind with natural
      consortium TR15 had greater microbial diversity and different microbial dynamics
      than cheese rinds with reconstituted consortia. Cheese rind with the natural
      consortium showed higher citrate consumption and the highest concentrations of
      lactic and acetic acids, connected with high levels of lactic acid bacteria such
      as Carnobacterium maltaromaticum, Vagococcus fluvialis, Enterococcus gilvus,
      Leuconostoc mesenteroides, Brochothrix thermosphacta and Lactococcus lactis,
      ripening bacteria such as Arthrobacter nicotianae/arilaitensis, and Gram negative
      bacteria (Pseudomonas psychrophila and Enterobacter spp.). The highest L.
      monocytogenes count was on rind with TR15-M and was positively associated with
      the highest pH value, high succinic and citric acid contents, and the highest
      levels of Marinilactibacillus psychrotolerans and Gram positive catalase positive
      bacteria represented by Staphylococcus vitulinus, Brevibacterium linens,
      Microbacterium gubbeenense and Brachybacterium tyrofermentans. The results show
      that the species composition of consortium is more important than the number of
      species. It is likely that inhibition mechanisms differ from one consortium to
      another; investigating gene expression will be an effective way to elucidate
      microbial interactions in cheese. 

PMID- 24463157
TI  - Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.)
      decoction extract in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Matricaria recutita L. (Chamomile) has been
      widely used in the Tunisian traditional medicine for the treatment of digestive
      system disorders. The present work aims to investigate the protective effects of
      chamomile decoction extract (CDE) against castor oil-induced diarrhea and
      oxidative stress in rats. METHODS: The antidiarrheal activity was evaluated using
      castor oil-induced diarrhea method. In this respect, rats were divided into six
      groups: Control, Castor oil, Castor oil+Loperamide (LOP) and Castor oil+various
      doses of CDE. Animals were per orally (p.o.) pre-treated with CDE during 1h and
      intoxicated for 2 or 4h by acute oral administration of castor oil. RESULTS: Our
      results showed that CDE produced a significant dose-dependent protection against
      castor oil-induced diarrhea and intestinal fluid accumulation. On the other hand,
      we showed that diarrhea was accompagned by an oxidative stress status assessed by
      an increase of malondialdehyde (MDA) level and depletion of antioxidant enzyme
      activities as superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPx). Castor oil also increased gastric and intestinal mucosa
      hydrogen peroxide (H2O2) and free iron levels. Importantly, we showed that
      chamomile pre-treatment abrogated all these biochemical alterations. CONCLUSION:
      These findings suggested that chamomile extract had a potent antidiarrheal and
      antioxidant properties in rats confirming their use in traditional medicine.

PMID- 24463158
TI  - Fruit-derived phenolic compounds and pancreatic cancer: perspectives from
      Australian native fruits.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pancreatic cancer is a devastating cancer that
      presents late, is rapidly progressive and has current therapeutics with only
      limited efficacy. Bioactive compounds are ubiquitously present in fruits and
      numerous studies in vitro are addressing the activity of these compounds against
      pancreatic cancer, thus studies of specific bioactive compounds could lead to new
      anti-pancreatic cancer strategies. Australian native fruits have been used as
      foods and medicines by Australian Aboriginals for thousands of years, and
      preliminary studies have found these fruits to contain rich and diversified
      bioactive components with high antioxidant activity. Thus, Australian native
      fruits may possess key components for preventing or delaying the onset of
      tumorigenesis, or for the treatment of existing cancers, including pancreatic
      cancer. MATERIALS AND METHODS: Numerous databases including PubMed, SciFinder,
      Web of Knowledge, Scopus, and Sciencedirect were analysed for correlations
      between bioactive components from fruits and pancreatic cancer, as well as
      studies concerning Australian native fruits. RESULTS: In this review, we
      comprehensively highlight the proposed mechanisms of action of fruit bioactives
      as anti-cancer agents, update the potential anti-pancreatic cancer activity of
      various major classes of bioactive compounds derived from fruits, and discuss the
      existence of bioactive compounds identified from a selection Australian native
      fruits for future studies. CONCLUSION: Bioactive compounds derived from fruits
      possess the potential for the discovery of new anti-pancreatic cancer strategies.
      Further, Australian native fruits are rich in polyphenols including some flora
      that contain unique phenolic compounds, thereby warranting further investigations
      into their anti-cancer properties.

PMID- 24463160
TI  - Cost-effectiveness of adding bevacizumab to first line therapy for patients with
      advanced ovarian cancer.
AB  - OBJECTIVE: To evaluate, from a societal perspective, the cost-effectiveness of
      adding bevacizumab to first-line therapy based on outcomes from the GOG-218 and
      ICON-7 trials. METHODS: A three-state Markov model was used. The time horizon was
      until the death of 99% of the initial cohort of 1000 individuals. Costs and
      quality-adjusted life-years (QALYs) were discounted at an annual rate of 3%. All
      costs were adjusted to 2013 USD. The incremental cost-effectiveness ratio (ICER)
      was reported as incremental cost per QALY gained. The robustness of the result
      was checked with one-way sensitivity analyses and for relevant clinical
      situations (i.e. varying the drug of choice to treat cancer recurrence). Subgroup
      analysis was conducted to identify subgroup of population for whom the strategy
      could be cost-effective. The potential impact of biosimilar bevacizumab was
      considered, using a 30% price reduction. RESULTS: For the GOG-218 study protocol,
      widely followed in US, the addition of bevacizumab results in an ICER of
      $2,420,691/QALY. For the ICON-7 study protocol, the ICER is $225,515/QALY. The
      results of the model were sensitive to the quality of life (QoL) and the median
      progression free survival (PFS). Biosimilar bevacizumab didn't reduce cost
      sufficiently to change conclusions. First-line augmentation is cost-effective,
      with biosimilar bevacizumab, for stage IV patients ($126,169/QALY), ECOG PS1
      patients ($116,575/QALY) and for patients with suboptimal residual disease
      ($122,822/QALY) as per the ICON-7 protocol. CONCLUSION: Addition of bevacizumab,
      by in large, is cost-ineffective. It can become cost-effective with the ICON-7
      protocol, in patients at high risk of progression using biosimilar bevacizumab.

PMID- 24463161
TI  - [Minimally invasive breast surgery].
AB  - Due to the development in medical science and industrial technology, minimally
      invasive procedures have appeared in the surgery of benign and malignant breast
      diseases. In general , such interventions result in significantly reduced breast
      and chest wall scars, shorter hospitalization and less pain, but they require
      specific, expensive devices, longer surgical time compared to open surgery.
      Furthermore, indications or oncological safety have not been established yet. It
      is quite likely, that minimally invasive surgical procedures with high-tech
      devices - similar to other surgical subspecialties -, will gradually become
      popular and it may form part of routine breast surgery even. Vacuum-assisted core
      biopsy with a therapeutic indication is suitable for the removal of benign
      fibroadenomas leaving behind an almost invisible scar, while endoscopically
      assisted skin-sparing and nipple-sparing mastectomy, axillary staging and
      reconstruction with latissimus dorsi muscle flap are all feasible through the
      same short axillary incision. Endoscopic techniques are also suitable for the
      diagnostics and treatment of intracapsular complications of implant-based breast
      reconstructions (intracapsular fluid, implant rupture, capsular contracture) and
      for the biopsy of intracapsular lesions with uncertain pathology. Perception of
      the role of radiofrequency ablation of breast tumors requires further hands-on
      experience, but it is likely that it can serve as a replacement of surgical
      removal in a portion of primary tumors in the future due to the development in
      functional imaging and anticancer drugs. With the reduction of the price of
      ductoscopes routine examination of the ductal branch system, guided
      microdochectomy and targeted surgical removal of terminal ducto-lobular units or
      a "sick lobe" as an anatomical unit may become feasible. The paper presents the
      experience of the authors and provides a literature review, for the first time in
      Hungarian language on the subject. Orv. Hetil., 2014, 155(5), 162-169. 

PMID- 24463159
TI  - TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy
      in patients with advanced ovarian cancer.
AB  - OBJECTIVE: TP53 K351N mutation is associated with acquired cisplatin resistance
      in ovarian cancer cells following exposure to cisplatin. We investigated the
      effect of TP53 K351N mutation on outcome in patients with epithelial ovarian
      cancer (EOC) who received platinum-based chemotherapy. METHODS: We assessed TP53
      K351N mutations by allele specific real-time PCR (AS-PCR) and DNA sequencing in
      tumor samples of 153 patients with stage IIIC/IV EOC. Clinicopathologic and
      follow-up data were collected by a retrospective chart review. RESULTS: TP53
      K351N mutations were detected in 8 (11.27%) of 71 patients who underwent
      neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) but not in 82
      patients who underwent primary debulking surgery (PDS) (P<0.01). In patients with
      relapse within 6 months, the relapse rate was 14 (19.72%) of 71 patients for NACT
      IDS compared to 15 (18.29%) of 82 patients for PDS (P=0.49), and TP53 K351N
      mutation was observed in 8 of NACT-IDS 14 patients (57.14% P<0.01). In the
      patients retreated at first recurrence within 6 months, 7 with TP53 K351N
      mutation of 14 NACT-IDS patients exhibited progression of disease, compared to 2
      of PDS 15 patients (50.00% vs. 13.33%, P=0.04). The median disease-free survival
      (DFS) for NACT-IDS was 13.0 months compared to 15.0 months for PDS (P=0.02). In
      multivariate analysis, TP53 K351N mutation is an independent factor for shorter
      DFS in the patients who underwent NACT-IDS (HR=19.05; P=0.01). CONCLUSIONS: TP53
      K351N mutation may be associated with induction of platinum resistance after NACT
      in advanced EOC.

PMID- 24463162
TI  - [Occupational rhinitis and allergic conjunctivitis].
AB  - Occupational rhinitis is an inflammatory disease of the nose, which is
      characterised by intermittent or persistent symptoms, arising from causes and
      conditions attributable to a particular work environment and not from stimuli
      encountered outside the workplace. Its clinical symptoms such as nasal
      congestion, sneezing, rhinorrhoea, itching, nasal airflow limitation are very
      similar to the symptoms of allergic rhinitis caused by other (classical) agents.
      Occupational allergic conjunctivitis is an IgE mediated disease, provoked by a
      substance in the air of the workplace. Its clinical signs (itching, tearing,
      conjunctival hyperaemia and oedema and, in some cases when the cornea is also
      involved, blurred vision, photosensitivity) are similar to other forms of
      allergic conjunctivitis. Risk factors (which in most of the cases occur in both
      diseases) include history of atopy, high concentration of the irritant agent and
      multiple irritant agents in the air of the workplace. Atopy has been associated
      with an increased risk of specific sensitisation to a variety of high molecular
      weight agents. For the diagnosis of occupational rhinitis and occupational
      allergic conjunctivitis objective investigations such as allergen specific
      provocations are necessary in addition to clinical and occupational history.
      Management of these occupational diseases needs environmental interventions
      (increasing ventilation, decreasing the time of exposure, substitution of the
      irritant agent). Medical treatment of occupational rhinitis is very similar to
      other allergic diseases: oral antihistamines, local (nasal) corticosteroids,
      combined (antihistamine plus membrane stabilizer) eyedrops. The most important
      step in medical treatment of occupational allergic conjunctivitis is the daily
      application of combined eyedrops (for example: olopatadine). Orv. Hetil., 2014,
      155(5), 170-175. 

PMID- 24463163
TI  - [Efficacy and safety of apixaban compared with warfarin regarding time within the
      therapeutic range].
AB  - Prevention of thromboembolism by lifelong anticoagulation is an important
      therapeutic goal in patients with atrial fibrillation according to recent
      guidelines. Major drawback of vitamin K antagonists are their narrow therapeutic
      range and interactions with other drugs and food. These have significant impact
      on the pharmacokinetics and pharmacodynamics requiring regular measurements of
      the international normalized ratio. Efficiency of the anticoagulant therapy
      depends considerably on time within the therapeutic range of prothrombin
      international normalized ratio. Time within the therapeutic range represents the
      percentage of time within the required range of prothrombin international
      normalized ratio. Prothrombin international normalized ratio outside the
      therapeutic range increases the risk of thromboembolism or bleeding according to
      whether it falls below or above the range. New oral anticoagulants do not require
      routine monitoring of anticoagulation. Their efficacy and safety are shown to be
      at least as good as or better than those of warfarin. In patients with
      nonvalvular atrial fibrillation ARISTOTLE study revealed that antithrombotic
      effect of apixaban compared with warfarin is better and with lower bleeding risk
      irrespective of the quality of prothrombin international normalized ratio
      control. Orv. Hetil., 2014, 155(5), 177-181. 

PMID- 24463164
TI  - [Experience with multidisciplinary laparoscopic surgery in patients with deep
      infiltrating colorectal endometriosis].
AB  - INTRODUCTION: Deep infiltrating endometriosis is a particular form of
      endometriosis that penetrates the peritoneal surface or it reaches the subserosal
      neurovascular plexus. AIM: The aim of the authors was to analyze the results of
      segmental colorectal resections performed for deep infiltrating endometriosis.
      METHOD: Between 2009 and 2012, 50 patients underwent segmental rectum or/and
      sigmoid resection for endometriosis. RESULTS: 21 patients had ultralow rectal
      resection and 29 patients had low colorectal anastomosis or anterior resection.
      Concomitant intervention in other organs was required in all cases, including
      gynecologic procedures (n = 50), additional gynecologic (n = 47), vesical (n = 9)
      and ureteral (n = 18) resections. The mean number of endometriosis lesions was
      2.4+/-1.8 per patient. In all patients fertility was preserved. Severe surgical
      complications (Clavien-Dindo stage III or more severe) occurred in 3 patients
      (6%). CONCLUSIONS: The results confirm that segmental bowel resection is an
      efficient and safe method for the treatment of deep infiltrating colorectal
      endometriosis. Orv. Hetil., 2014, 155(5), 182-186.

PMID- 24463165
TI  - [Relationship between early myocardial reperfusion assessed by videodensitometry
      and late left ventricular function. Results following invasive treatment of acute
      myocardial infarction].
AB  - INTRODUCTION: It is known that there is a relationship between myocardial
      perfusion and left ventricular function. AIM: The aim of the current study was to
      examine the relationship between myocardial reperfusion as assessed by
      videodensitometry on coronary angiograms following invasive treatment of ST
      elevation myocardial infarction and magnetic resonance imaging-derived late left
      ventricular function. METHOD: The study included 25 patients with ST elevation
      myocardial infarction. A quantitative parameter of myocardial (re)perfusion was
      calculated by the ratio of maximal density (Gmax) and the time to reach maximum
      density (Tmax) following invasive treatment. Magnetic resonance imaging was
      performed 387+/-262 days after ST elevation myocardial infarction for the
      evaluation of left ventricular function in all cases. RESULTS: Significant
      correlations were demonstrated between left ventricular ejection fraction and
      Gmax (r = 0.40, p = 0.05) and Gmax/Tmax (r = 0.41, p = 0.04) following vessel
      masking. CONCLUSIONS: The results demonstrate significant relationship between
      densitometric Gmax/Tmax and late left ventricular function following ST elevation
      myocardial infarction. Orv. Hetil., 2014. 155(5), 187-193.

PMID- 24463166
TI  - [Treatment of metastatic midgut neuroendocrine tumour associated with carcinoid
      syndrome].
AB  - Although the incidence of neuroendocrine tumours is low, their prevalence is high
      due to the usually slow course of the disease. Between July 1, 2008 and July 1,
      2013 the authors evaluated 56 patients with well-differentiated or moderately
      differentiated neuroendocrine tumours; 36 patients with metastatic disease
      underwent treatment while 17 patients who had tumour resection were followed
      without additional treatment. All patients with metastatic disease received long
      acting octreotide, and additional therapy was based on the site of origin, grade
      of differentiation, Ki67 index, and focal labelling of the tumours during
      somatostatin-receptor or metaiodo-benzyl-guanidine scintigraphy. The authors
      present a detailed case history of a patient with carcinoid syndrome due to a
      metastatic midgut neuroendocrine tumour, who received long acting octreotide and
      peptide receptor radionuclide treatment. In this patient an objective tumour
      response was reached in addition to the resolution of symptoms of carcinoid
      syndrome. The authors conclude that the case history confirms previous
      observations showing that long acting octreotide combined with peptide receptor
      radionuclide treatment may provide long survival with good quality of life in a
      patient with metastatic midgut neuroendocrine tumour accompanied with carcinoid
      syndrome. Orv. Hetil., 2014, 155(5), 194-198. 

PMID- 24463167
TI  - [Miscellaneous].

PMID- 24463168
TI  - A novel valproic acid prodrug as an anticancer agent that enhances doxorubicin
      anticancer activity and protects normal cells against its toxicity in vitro and
      in vivo.
AB  - The poor survival of patients with malignant gliomas, underscores the need to
      develop effective treatment modalities for this devastating disease. Epigenetic
      agents used in combination with chemotherapy provide a promising approach to
      evoke synergistic cytotoxicity in glioblastomas. Previously we have described the
      cytotoxic synergy between a butyric acid prodrug and radiation in glioblastoma
      cell lines and the potentiation of radiation efficacy in glioma xenografts.
      Herein, we describe and compare the activities of AN446 (valproyl ester
      valpramide of acyclovir) a novel histone deacetylase inhibitor (HDACI) to the
      previously described AN7 a HDACI prodrug of butyric acid. In various cancer cell
      lines, AN446 was a ~2-5-fold more potent anticancer agent HDACI than AN7. While
      AN446 augmented the anticancer efficacy of doxorubicin (Dox) it also reduced the
      Dox toxicity in non-cancerous cells. The interaction between AN446 and Dox in
      U251 and in 4T1 cell lines was synergistic in inducing cytotoxicity. We examined
      the concomitant physical and molecular changes in the tumor and heart of
      glioblastoma xenografts treated with AN446, AN7, Dox and the combination of the
      prodrugs with Dox. A weekly dose of 4 mg/kg Dox, caused toxicity in mice whereas
      AN446 (25mg/kg) or AN7 (50mg/kg) administered thrice weekly, did not. When Dox
      was administered with AN446 or AN7, the prodrugs ameliorated the decline in body
      weight, prolonged the time to failure and increased anticancer efficacy. Thus,
      the combination of Dox with AN446 or AN7 could add safety and efficacy to future
      treatment protocols for treating glioblastoma and other cancers.

PMID- 24463169
TI  - Intraspecific venom variation in the medically significant Southern Pacific
      Rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary
      implications.
AB  - Due to the extreme variation of venom, which consequently results in drastically
      variable degrees of neutralization by CroFab antivenom, the management and
      treatment of envenoming by Crotalus oreganus helleri (the Southern Pacific
      Rattlesnake), one of the most medically significant snake species in all of North
      America, has been a clinician's nightmare. This snake has also been the subject
      of sensational news stories regarding supposed rapid (within the last few
      decades) evolution of its venom. This research demonstrates for the first time
      that variable evolutionary selection pressures sculpt the intraspecific molecular
      diversity of venom components in C. o. helleri. We show that myotoxic beta
      defensin peptides (aka: crotamines/small basic myotoxic peptides) are secreted in
      large amounts by all populations. However, the mature toxin-encoding nucleotide
      regions evolve under the constraints of negative selection, likely as a result of
      their non-specific mode of action which doesn't enforce them to follow the regime
      of the classic predator-prey chemical arms race. The hemorrhagic and tissue
      destroying snake venom metalloproteinases (SVMPs) were secreted in larger amounts
      by the Catalina Island and Phelan rattlesnake populations, in moderate amounts in
      the Loma Linda population and in only trace levels by the Idyllwild population.
      Only the Idyllwild population in the San Jacinto Mountains contained potent
      presynaptic neurotoxic phospholipase A2 complex characteristic of Mohave
      Rattlesnake (Crotalus scutulatus) and Neotropical Rattlesnake (Crotalus durissus
      terrificus). The derived heterodimeric lectin toxins characteristic of viper
      venoms, which exhibit a diversity of biological activities, including
      anticoagulation, agonism/antagonism of platelet activation, or procoagulation,
      appear to have evolved under extremely variable selection pressures. While most
      lectin alpha- and beta-chains evolved rapidly under the influence of positive
      Darwinian selection, the beta-chain lectin of the Catalina Island population
      appears to have evolved under the constraint of negative selection. Both lectin
      chains were conspicuously absent in both the proteomics and transcriptomics of
      the Idyllwild population. Thus, we not only highlight the tremendous biochemical
      diversity in C. o. helleri's venom-arsenal, but we also show that they experience
      remarkably variable strengths of evolutionary selection pressures, within each
      toxin class among populations and among toxin classes within each population. The
      mapping of geographical venom variation not only provides additional information
      regarding venom evolution, but also has direct medical implications by allowing
      prediction of the clinical effects of rattlesnake bites from different regions.
      Such information, however, also points to these highly variable venoms as being a
      rich source of novel toxins which may ultimately prove to be useful in drug
      design and development. BIOLOGICAL SIGNIFICANCE: These results have direct
      implications for the treatment of envenomed patients. The variable venom profile
      of Crotalus oreganus helleri underscores the biodiscovery potential of novel
      snake venoms.

PMID- 24463170
TI  - Identification of motives mediating alternative functions of the neomorphic
      moonlighting TPPP/p25.
AB  - The disordered Tubulin Polymerization Promoting Protein (TPPP/p25), a prototype
      of neomorphic moonlighting proteins, displays physiological and pathological
      functions by interacting with distinct partners. Here the role of the disordered
      N- and C-termini straddling a middle flexible segment in the distinct functions
      of TPPP/p25 was established, and the binding motives responsible for its
      heteroassociations with tubulin and alpha-synuclein, its physiological and
      pathological interacting partner, respectively, were identified. We showed that
      the truncation of the disordered termini altered the folding state of the middle
      segment and has functional consequences concerning its physiological function.
      Double truncation diminished its binding to tubulin/microtubules, consequently
      the tubulin polymerization/microtubule bundling activities of TPPP/p25 were lost
      highlighting the role of the disordered termini in its physiological function. In
      contrast, interaction of TPPP/p25 with alpha-synuclein was not affected by the
      truncations and its alpha-synuclein aggregation promoting activity was preserved,
      showing that the alpha-synuclein binding motif is localized within the middle
      segment. The distinct tubulin and alpha-synuclein binding motives of TPPP/p25
      were also demonstrated at the cellular level: the double truncated TPPP/p25 did
      not align along the microtubules in contrast to the full length form, while it
      induced alpha-synuclein aggregation. The localization of the binding motives on
      TPPP/p25 were established by specific ELISA experiments performed with designed
      and synthesized peptides: motives at the 178-187 and 147-156 segments are
      involved in the binding of tubulin and alpha-synuclein, respectively. The
      dissimilarity of these binding motives responsible for the neomorphic
      moonlighting feature of TPPP/p25 has significant innovative impact in anti
      Parkinson drug research. 

PMID- 24463171
TI  - Molecular cloning and knockdown of galactocerebrosidase in zebrafish: new
      insights into the pathogenesis of Krabbe's disease.
AB  - The lysosomal hydrolase galactocerebrosidase (GALC) catalyzes the removal of
      galactose from galactosylceramide and from other sphingolipids. GALC deficiency
      is responsible for globoid cell leukodystrophy (GLD), or Krabbe's disease, an
      early lethal inherited neurodegenerative disorder characterized by the
      accumulation of the neurotoxic metabolite psychosine in the central nervous
      system (CNS). The poor outcome of current clinical treatments calls for novel
      model systems to investigate the biological impact of GALC down-regulation and
      for the search of novel therapeutic strategies in GLD. Zebrafish (Danio rerio)
      represents an attractive vertebrate model for human diseases. Here, lysosomal
      GALC activity was demonstrated in the brain of zebrafish adults and embryos.
      Accordingly, we identified two GALC co-orthologs (named galca and galcb)
      dynamically co-expressed in CNS during zebrafish development. Both genes encode
      for lysosomal enzymes endowed with GALC activity. Single down-regulation of galca
      or galcb by specific antisense morpholino oligonucleotides results in a partial
      decrease of GALC activity in zebrafish embryos that was abrogated in double
      galca/galcb morphants. However, no psychosine accumulation was observed in
      galca/galcb double morphants. Nevertheless, double galca/galcb knockdown caused
      reduction and partial disorganization of the expression of the early neuronal
      marker neuroD and an increase of apoptotic events during CNS development. These
      observations provide new insights into the pathogenesis of GLD, indicating that
      GALC loss-of-function may have pathological consequences in developing CNS
      independent of psychosine accumulation. Also, they underscore the potentiality of
      the zebrafish system in studying the pathogenesis of lysosomal neurodegenerative
      diseases, including GLD.

PMID- 24463172
TI  - Photochemical fate of solvent constituents of Corexit oil dispersants.
AB  - In 2010, an estimated 1.87 million gallons (7079 cubic meters) of chemical
      dispersants were applied to open ocean waters in the Gulf of Mexico as part of
      the response to the Deepwater Horizon blowout. This unprecedented volume of
      dispersant application highlighted the importance of dispersant chemical
      formulations, raising questions of dispersant fate and transport in the open
      ocean and spurring research into formulation improvements. The research presented
      here elucidates the contribution of photolytic processes to the degradation of
      two solvent constituents of these dispersant mixtures: propylene glycol (PG) and
      2-butoxyethanol (2-BE). A series of photodegradation experiments were conducted
      to determine the contribution of direct photolysis and indirect photolysis via
      hydroxyl radical (HO) to compound degradation. Experiments were performed using
      both deep UV light sources (low pressure (LP) and medium pressure (MP) mercury
      vapor ultraviolet (UV) lamps) and a solar simulator. Sample matrices included
      ultrapure water, nitrate amended water, hydrogen peroxide (H2O2) spiked water,
      Gulf of Mexico seawater, and a surface water from Boulder, CO. Experiments
      included determination of the molar absorption coefficients (epsilon) and the HO
      reaction rate constants (kHO) of the individual compounds. Data illustrated that
      significant direct photolysis of either PG or 2-BE from sunlight is unlikely. The
      kHO for PG and 2-BE were determined to be 6.15 * 10(8) M(-1) s(-1) and 1.15 *
      10(9) M(-1) s(-1), respectively. Solar simulation and UV experiments indicate
      that in natural systems, neither PG nor 2-BE is expected to undergo significant,
      rapid degradation due to direct or indirect photolysis. PG and 2-BE are
      effectively degraded through indirect photolysis in the presence of high HO
      concentrations, suggesting UV/H2O2 is a feasible possibility for the treatment of
      waters containing PG and 2-BE. 

PMID- 24463173
TI  - Photodegradation of the azole fungicide fluconazole in aqueous solution under UV
      254: kinetics, mechanistic investigations and toxicity evaluation.
AB  - The azole fungicide fluconazole has been reported to be persistent in
      conventional wastewater treatment plants. This study investigated the
      photodegradation of fluconazole under UV-254 in aqueous solutions. The results
      revealed that the photodegradation of fluconazole was pH-dependent (2.0-12.0)
      following the pseudo-first-order kinetics with quantum yield values ranging from
      0.023 to 0.090 mol einstein(-1), and it underwent a direct and self-sensitized
      mechanism involving (1)O2. The main photodegradation by-products were identified
      and semi-quantitated. The proposed photodegradation pathway included
      hydroxylative defluorination reaction. The 72 h-NOEC and 72 h-LOEC values for
      fluconazole using a freshwater unicellular green alga Pseudokirchneriella
      subcapitata were 10 MUM and 15 MUM. Overall, the photodegradation of fluconazole
      produced a significant decrease in algal toxicity. It also proved that the
      photodegradation by-products will not present extra toxicity to this alga than
      fluconazole itself. 

PMID- 24463174
TI  - Anoxic and oxic removal of humic acids with Fe@Fe2O3 core-shell nanowires: a
      comparative study.
AB  - In this study we comparatively investigate the removal of humic acids with
      Fe@Fe2O3 core-shell nanowires under anoxic and oxic conditions. The products of
      humic acids after reacting with Fe@Fe2O3 core-shell nanowires under anoxic and
      oxic conditions were carefully examined with three-dimensional excitation
      emission matrix fluorescence spectroscopy and gas chromatography mass
      spectrometry. It was found that humic acids were removed by Fe@Fe2O3 core-shell
      nanowires via adsorption under anoxic condition. Langmuir adsorption isotherm was
      applicable to describe the adsorption processes. Kinetics of humic acids
      adsorption onto Fe@Fe2O3 core-shell nanowires was found to follow pseudo-second
      order rate equation. By contrast, the oxic removal of humic acids with Fe@Fe2O3
      core-shell nanowires involved adsorption and subsequent oxidation of humic acids
      because Fe@Fe2O3 core-shell nanowires could activate molecular oxygen to produce
      reactive oxygen species to oxidize humic acids. This subsequent oxidation of
      humic acids could improve the oxic removal rate to 2.5 times that of anoxic
      removal, accompanying with about 8.4% of mineralization. This study provides a
      new method for humic acids removal and also sheds light on the effects of humic
      acids on the pollutant removal by nano zero-valent iron. 

PMID- 24463175
TI  - Sustainable water recovery from oily wastewater via forward osmosis-membrane
      distillation (FO-MD).
AB  - This study proposed and investigated a hybrid forward osmosis - membrane
      distillation (FO-MD) system for sustainable water recovery from oily wastewater
      by employing lab-fabricated FO and MD hollow fiber membranes. Stable oil-in-water
      emulsions of different concentrations with small droplet sizes (<1 MUm) were
      firstly prepared and applied as the feed solution in the FO process. Fouling was
      immediately observed in the FO mode and was low on the cellulose triacetate (CTA)
      - based thin film composite (TFC) membranes. Moreover, slight increment of
      fouling was observed in the first few hours and the water flux was then
      stabilized over 24 h. The characterizations of water flux and solute rejection in
      separate FO and MD processes revealed that a high water flux, good NaCl
      rejection, impressively high retention of oil droplets and partial permeation of
      acetic acid could be achieved. Finally, an integrated FO-MD system was developed
      to treat the oily wastewater containing petroleum, surfactant, NaCl and acetic
      acid at 60  degrees C in the batch mode. The water flux in FO undergoes three
      stage decline due to fouling and reduction in osmotic driving force, but is quite
      stable in MD regardless of salt concentration. Oily wastewater with relatively
      high salinity could be effectively recovered by the FO-MD hybrid system while
      maintaining large water flux, at least 90% feed water recovery could be readily
      attained with only trace amounts of oil and salts, and the draw solution was re
      generated for the next rounds of FO-MD run. Interestingly, significant amount of
      acetic acid was also retained in the permeate for further reuse as a chemical
      additive during the production of crude oil. The work has demonstrated that not
      only water but also organic additives in the wastewater could be effectively
      recovered by FO-MD systems for reuse or other utilizations. 

PMID- 24463176
TI  - Assessing the decontamination efficiency of a three-component flocculating system
      in the treatment of oilfield-produced water.
AB  - Produced water is a complex mixture of oil, water, dissolved solids, and
      suspended solids. It represents the largest volume of waste associated with the
      oil and gas industry, and its management is a costly aspect of oil recovery.
      Therefore, the development of effective treatment technologies for produced water
      is essential from both ecological and economic standpoints. We have developed a
      sensitive, fluorescence-based method to demonstrate the decontamination
      efficiency of a three-component polymeric flocculating system, the
      microencapsulating flocculating dispersion (MFD) technology. We have shown that
      the MFD technology can remove 90 +/- 2% of the pyrene, a model wastewater
      contaminant, in a 0.4 ppm aqueous stock solution. The optimal flocculant
      concentrations used to remove pyrene was determined by fluorescence spectroscopy
      and zeta potential measurements. Under these conditions, flocculation and
      settling times were fast (i.e., <1 min). We have also demonstrated rapid removal
      of crude oil from an oilfield-produced water sample with a remarkable
      decontamination efficiency of >=98 +/- 1%. Using this fluorescence-based method,
      we will be better able to formulate the components of this technology and other
      polymeric flocculants in the treatment of oilfield-produced water, which will
      benefit wastewater treatment technologies. 

PMID- 24463177
TI  - Vacuum-UV radiation at 185 nm in water treatment--a review.
AB  - The vacuum-UV radiation of water results in the in situ generation of hydroxyl
      radicals. Low-pressure mercury vapor lamps which emit at 185 nm are potential
      sources of VUV radiation. The scope of this article is to give an overview of the
      application of VUV radiation at 185 nm for water treatment including the
      transformation of inorganic and organic water constituents, and the disinfection
      efficiency. Another focus is on the generation of ozone by VUV radiation from
      oxygen or air and the application of the produced ozone in combination with VUV
      irradiation of water in the VUV/O3 process. The advantages and limitation of the
      VUV process at 185 nm as well as possible applications in water treatment are
      outlined. 

PMID- 24463178
TI  - Mechanisms underlying the vascular and hypotensive actions of the labdane ent-3
      acetoxy-labda-8(17),13-dien-15-oic acid.
AB  - We investigated the mechanisms underlying the vasorelaxant and hypotensive
      actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17),13-dien-15-oic
      acid (labda-15-oic acid). Vascular reactivity experiments were performed in
      aortic rings isolated from male Wistar rats. cAMP and cGMP were measured by
      enzyme immunoassay (EIA) whereas nitrate measurement was performed by
      chemiluminescence. Nitric oxide (NO) concentration ([NO]c) was measured in
      endothelial cells by flow cytometry. The cytosolic calcium concentration
      ([Ca2+]c) in vascular smooth muscle cells (VSMC) was measured by confocal
      microscopy. Blood pressure measurements were performed in conscious rats. Labda
      15-oic acid inhibited the contraction induced by phenylephrine and serotonin in
      either endothelium-intact or endothelium-denuded rat aortic rings. The labdane
      significantly reduced CaCl2-induced contraction in a Ca2+-free solution
      containing KCl or phenylephrine. Labda-15-oic acid (0.1-300 MUmol/l)
      concentration-dependently relaxed endothelium-intact and endothelium-denuded
      aortas pre-contracted with either phenylephrine or KCl. In endothelium-intact
      rings, the relaxation induced by labda-15-oic acid was affected by L-NAME, 7
      nitroindazole, ODQ, hemoglobin, Rp-8-Br-Pet-cGMPS and thapsigargin. Blockade of
      K+ channels with 4-aminopyridine, apamin, charybdotoxin and glibenclamide
      affected the relaxation induced by labda-15-oic acid. The labdane increased cGMP
      and nitrate levels but did not affect cAMP levels in endothelium-intact aortas.
      Labda-15-oic acid increased [NO]c in endothelial cells and decreased [Ca2+]c in
      VSMC. The hypotension induced by intravenous administration of labda-15-oic acid
      (0.3-3 mg/kg) was partially reduced by L-NAME. In conclusion, the mechanisms
      underlying the cardiovascular actions of the labdane involve the activation of
      the endothelial NO-cGMP pathway, the opening of K+ channels and the alteration on
      Ca2+ mobilization.

PMID- 24463179
TI  - Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat
      model.
AB  - Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and
      morbidity in neonates, and there is currently no effective therapy for HIBD.
      Carnosine plays a neuroprotective role in adult brain damage. We have previously
      demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat
      model. Therefore, we hypothesized that treatment with carnosine would also have
      neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7
      9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at
      0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of
      oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was
      induced, Brain learning and memory function performance were observed using the
      Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine
      post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha
      in brain tissue and decreased the number of terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and
      cortex as well as the mitochondria caspase-3 protein expression. Furthermore,
      carnosine also improved the cognitive function of P28-33 rats, whose cognitive
      function decline was due to HIBD. These results demonstrate that carnosine
      treatment after HIBD can reduce the brain injury, improving brain function.
      Carnosine could be an attractive candidate for treating HIBD. 

PMID- 24463180
TI  - Combinatorial therapy discovery using mixed integer linear programming.
AB  - MOTIVATION: Combinatorial therapies play increasingly important roles in
      combating complex diseases. Owing to the huge cost associated with experimental
      methods in identifying optimal drug combinations, computational approaches can
      provide a guide to limit the search space and reduce cost. However, few
      computational approaches have been developed for this purpose, and thus there is
      a great need of new algorithms for drug combination prediction. RESULTS: Here we
      proposed to formulate the optimal combinatorial therapy problem into two
      complementary mathematical algorithms, Balanced Target Set Cover (BTSC) and
      Minimum Off-Target Set Cover (MOTSC). Given a disease gene set, BTSC seeks a
      balanced solution that maximizes the coverage on the disease genes and minimizes
      the off-target hits at the same time. MOTSC seeks a full coverage on the disease
      gene set while minimizing the off-target set. Through simulation, both BTSC and
      MOTSC demonstrated a much faster running time over exhaustive search with the
      same accuracy. When applied to real disease gene sets, our algorithms not only
      identified known drug combinations, but also predicted novel drug combinations
      that are worth further testing. In addition, we developed a web-based tool to
      allow users to iteratively search for optimal drug combinations given a user
      defined gene set. AVAILABILITY: Our tool is freely available for noncommercial
      use at http://www.drug.liuzlab.org/. CONTACT: zhandong.liu@bcm.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 24463181
TI  - Cas-OFFinder: a fast and versatile algorithm that searches for potential off
      target sites of Cas9 RNA-guided endonucleases.
AB  - SUMMARY: The Type II clustered regularly interspaced short palindromic repeats
      (CRISPR)/Cas system is an adaptive immune response in prokaryotes, protecting
      host cells against invading phages or plasmids by cleaving these foreign DNA
      species in a targeted manner. CRISPR/Cas-derived RNA-guided engineered nucleases
      (RGENs) enable genome editing in cultured cells, animals and plants, but are
      limited by off-target mutations. Here, we present a novel algorithm termed Cas
      OFFinder that searches for potential off-target sites in a given genome or user
      defined sequences. Unlike other algorithms currently available for identification
      of RGEN off-target sites, Cas-OFFinder is not limited by the number of mismatches
      and allows variations in protospacer-adjacent motif sequences recognized by Cas9,
      the essential protein component in RGENs. Cas-OFFinder is available as a command
      line program or accessible via our website. AVAILABILITY AND IMPLEMENTATION: Cas
      OFFinder free access at http://www.rgenome.net/cas-offinder. CONTACT:
      baesau@snu.ac.kr or jskim01@snu.ac.kr.

PMID- 24463182
TI  - ECplot: an online tool for making standardized plots from large datasets for
      bioinformatics publications.
AB  - MOTIVATION AND RESULTS: We have implemented ECplot, an online tool for plotting
      charts from large datasets. This tool supports a variety of chart types commonly
      used in bioinformatics publications. In our benchmarking, it was able to create a
      Box-and-Whisker plot with about 67 000 data points and 8 MB total file size
      within several seconds. The design of the tool makes common formatting operations
      easy to perform. It also allows more complex operations to be achieved by
      advanced XML (Extensible Markup Language) and programming options. Data and
      formatting styles are stored in separate files, such that style templates can be
      made and applied to new datasets. The text-based file formats based on XML
      facilitate efficient manipulation of formatting styles for a large number of data
      series. These file formats also provide a means to reproduce published figures
      from raw data, which complement parallel efforts in making the data and software
      involved in published analysis results accessible. We demonstrate this idea by
      using ECplot to replicate some complex figures from a previous publication.
      AVAILABILITY AND IMPLEMENTATION: ECplot and its source code (under MIT license)
      are available at https://yiplab.cse.cuhk.edu.hk/ecplot/. CONTACT:
      kevinyip@cse.cuhk.edu.hk.

PMID- 24463183
TI  - G-BLASTN: accelerating nucleotide alignment by graphics processors.
AB  - MOTIVATION: Since 1990, the basic local alignment search tool (BLAST) has become
      one of the most popular and fundamental bioinformatics tools for sequence
      similarity searching, receiving extensive attention from the research community.
      The two pioneering papers on BLAST have received over 96 000 citations. Given the
      huge population of BLAST users and the increasing size of sequence databases, an
      urgent topic of study is how to improve the speed. Recently, graphics processing
      units (GPUs) have been widely used as low-cost, high-performance computing
      platforms. The existing GPU-BLAST is a promising software tool that uses a GPU to
      accelerate protein sequence alignment. Unfortunately, there is still no GPU
      accelerated software tool for BLAST-based nucleotide sequence alignment. RESULTS:
      We developed G-BLASTN, a GPU-accelerated nucleotide alignment tool based on the
      widely used NCBI-BLAST. G-BLASTN can produce exactly the same results as NCBI
      BLAST, and it has very similar user commands. Compared with the sequential NCBI
      BLAST, G-BLASTN can achieve an overall speedup of 14.80X under 'megablast' mode.
      More impressively, it achieves an overall speedup of 7.15X over the multithreaded
      NCBI-BLAST running on 4 CPU cores. When running under 'blastn' mode, the overall
      speedups are 4.32X (against 1-core) and 1.56X (against 4-core). G-BLASTN also
      supports a pipeline mode that further improves the overall performance by up to
      44% when handling a batch of queries as a whole. Currently G-BLASTN is best
      optimized for databases with long sequences. We plan to optimize its performance
      on short database sequences in our future work. AVAILABILITY:
      http://www.comp.hkbu.edu.hk/~chxw/software/G-BLASTN.html CONTACT:
      chxw@comp.hkbu.edu.hk SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 24463184
TI  - Modeling tissue contamination to improve molecular identification of the primary
      tumor site of metastases.
AB  - MOTIVATION: Contamination of a cancer tissue by the surrounding benign (non
      cancerous) tissue is a concern for molecular cancer diagnostics. This is because
      an observed molecular signature will be distorted by the surrounding benign
      tissue, possibly leading to an incorrect diagnosis. One example is molecular
      identification of the primary tumor site of metastases because biopsies of
      metastases typically contain a significant amount of benign tissue. RESULTS: A
      model of tissue contamination is presented. This contamination model works
      independently of the training of a molecular predictor, and it can be combined
      with any predictor model. The usability of the model is illustrated on primary
      tumor site identification of liver biopsies, specifically, on a human dataset
      consisting of microRNA expression measurements of primary tumor samples, benign
      liver samples and liver metastases. For a predictor trained on primary tumor and
      benign liver samples, the contamination model decreased the test error on
      biopsies from liver metastases from 77 to 45%. A further reduction to 34% was
      obtained by including biopsies in the training data. AVAILABILITY AND
      IMPLEMENTATION: http://www.math.ku.dk/~richard/msgl/. CONTACT: vincent@math.ku.dk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24463185
TI  - Comparison of approaches for parameter identifiability analysis of biological
      systems.
AB  - MOTIVATION: Modeling of dynamical systems using ordinary differential equations
      is a popular approach in the field of Systems Biology. The amount of experimental
      data that are used to build and calibrate these models is often limited. In this
      setting, the model parameters may not be uniquely determinable. Structural or a
      priori identifiability is a property of the system equations that indicates
      whether, in principle, the unknown model parameters can be determined from the
      available data. RESULTS: We performed a case study using three current approaches
      for structural identifiability analysis for an application from cell biology. The
      approaches are conceptually different and are developed independently. The
      results of the three approaches are in agreement. We discuss strength and
      weaknesses of each of them and illustrate how they can be applied to real world
      problems. AVAILABILITY AND IMPLEMENTATION: For application of the approaches to
      further applications, code representations (DAISY, Mathematica and MATLAB) for
      benchmark model and data are provided on the authors webpage. CONTACT:
      andreas.raue@fdm.uni-freiburg.de.

PMID- 24463186
TI  - Functional Recovery After Ischemic Stroke Is Associated With Reduced GABAergic
      Inhibition in the Cerebral Cortex: A GABA PET Study.
AB  - BACKGROUND: gamma-Aminobutyric acid (GABA) plasticity plays an important role in
      stroke motor recovery in a mouse model. However, little is known about changes
      over time in neuronal excitability mediated by GABA receptors in human stroke
      patients. OBJECTIVES: To establish the mechanism of neuroplasticity during the
      recovery phase following ischemic stroke by assessing the changes in cerebral
      GABA activity using [(18)F]flumazenil ([(18)F]FMZ) positron emission tomography
      (PET). METHODS: A total of 10 patients with unilateral ischemic stroke were
      studied at 1 month (T0) and 3 months (T1) postonset using [(18)F]FMZ PET. Changes
      in regional GABAergic activity were assessed longitudinally, and values were also
      compared with those in 15 age-matched controls. Upper-extremity motor function
      was evaluated using the Fugl-Meyer score (FMS). RESULTS: During the follow-up
      period, statistical parametric mapping analysis demonstrated a decrease in GABAA
      receptor availability throughout the cerebral cortex and cerebellum, especially
      the contralateral hemisphere. GABAA availability in the bilateral primary motor
      cortex, contralateral supplemental motor cortex, and globus pallidus at T0 was
      positively correlated with the FMS score at T1 CONCLUSIONS: This is the first
      prospective, controlled longitudinal study showing that the change in GABA
      receptor availability over time is significantly related to motor recovery after
      stroke in humans. This work supports the rationale for a novel strategy to
      promote motor recovery after stroke.

PMID- 24463187
TI  - A critical appraisal of intravenous fluids: from the physiological basis to
      clinical evidence.
AB  - Fluid management has been a vital part of routine clinical care for more than 180
      years. The increasing number of available fluids has generated controversy about
      the optimal choice of resuscitation fluid. In this review, we provide a critical
      overview of the different fluids available, their composition, the relevant
      physiology as well as the published evidence on clinical outcomes to guide their
      use. Commonly used infusion fluids include semisynthetic colloids and
      crystalloids; the latter comprises both normal saline (NaCl 0.9%) and the more
      chloride-restricted 'balanced' crystalloids. Despite their significantly greater
      intravascular persistence, semisynthetic colloids have an importantly adverse
      safety profile and are associated with greater incidence of renal failure and
      increased mortality; their use should be restricted. To date, evidence for
      clinical benefits associated with albumin solutions is generally lacking; its
      merits in specific clinical situations are the subject of further investigation.
      Infusion of normal saline, with its supraphysiological chloride content, is
      associated with higher serum chloride concentrations and metabolic acidosis, as
      well as renal vasoconstriction in animal and human models. Infusion of 'balanced'
      crystalloids is not linked to such changes. Although data on clinical outcomes
      associated with crystalloid infusion are heterogeneous, advantages of balanced
      salt solutions might include a lower need of blood products, and lower incidence
      of renal replacement therapy, hyperkalaemia and postoperative infections. Taken
      together, a critical appraisal of the data suggests that balanced salt solutions
      deserve consideration as infusates of first choice. 

PMID- 24463188
TI  - Endothelial-to-mesenchymal transition and renal fibrosis in ischaemia/reperfusion
      injury are mediated by complement anaphylatoxins and Akt pathway.
AB  - BACKGROUND: Increasing evidence demonstrates a phenotypic plasticity of
      endothelial cells (ECs). Endothelial-to-mesenchymal transition (EndMT)
      contributes to the development of tissue fibrosis. However, the pathogenic
      factors and signalling pathways regulating this process in ischaemia/reperfusion
      (I/R) injury are still poorly understood. METHODS: We investigated the possible
      role of complement in the induction of this endothelial dysfunction in a swine
      model of renal I/R injury by using recombinant C1 inhibitor in vivo. RESULTS:
      Here, we showed that I/R injury reduced the density of renal peritubular
      capillaries and induced tissue fibrosis with generation of CD31(+)/alpha-SMA(+)
      and CD31(+)/FPS-1(+) cells indicating EndMT. When we inhibited complement, the
      process of EndMT became rare, with preserved density of peritubular capillaries
      and significant reduction in renal fibrosis. When we activated ECs by
      anaphylatoxins in vitro, C3a and C5a led to altered endothelial phenotype with
      increased expression of fibroblast markers and decrease expression of specific
      endothelial markers. The activation of Akt pathway was pivotal for the C3a and
      C5a-induced EndMT in vitro. In accordance, inhibition of complement in vivo led
      to the abrogation of Akt signalling, with hampered EndMT and tissue fibrosis.
      CONCLUSIONS: Our data demonstrate a critical role for complement in the acute
      induction of EndMT via the Akt pathway. Therapeutic inhibition of these systems
      may be essential to prevent vascular damage and tissue fibrosis in transplanted
      kidney.

PMID- 24463189
TI  - Mechanisms and management of hypertension in autosomal dominant polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly
      inherited kidney disease, characterized by progressive cyst growth and renal
      enlargement, resulting in renal failure. Hypertension is common and occurs early,
      prior to loss of kidney function. Whether hypertension in ADPKD is a primary
      vasculopathy secondary to mutations in the polycystin genes or secondary to
      activation of the renin-angiotensin-aldosterone system by cyst expansion and
      intrarenal ischemia is unclear. Dysregulation of the primary cilium causing
      endothelial and vascular smooth muscle cell dysfunction is a component of ADPKD.
      In this article, we review the epidemiology, pathophysiology and clinical
      characteristics of hypertension in ADPKD and give specific recommendations for
      its treatment. 

PMID- 24463190
TI  - Impaired renal growth hormone JAK/STAT5 signaling in chronic kidney disease.
AB  - BACKGROUND: Treatment with recombinant human growth hormone (GH) is the standard
      therapy for short stature in children with chronic kidney disease (CKD). However,
      concerns have been raised on the potential renal fibrogenic effects of GH. There
      is no information regarding the renal GH receptor (GHR)-JAK-STAT signaling
      pathway in CKD. METHODS: Subtotal nephrectomized (CKD) and pair-fed sham-operated
      control (C) juvenile rats were treated with subcutaneous GH or saline for 2
      weeks. A single intravenous GH bolus or vehicle was provided prior to euthanasia.
      RESULTS: Reduced body weight in CKD was improved with GH therapy. The remnant
      kidney showed glomerular hypertrophy and early interstitial fibrosis without
      inflammatory infiltration. Treatment of CKD rats with GH did not worsen renal
      function or fibrosis. Kidney GHR mRNA and protein levels were reduced and basal
      phosphorylation of JAK2 and STAT5 was significantly impaired. However,
      intravenous GH administration prior to sacrifice normalized STAT5
      phosphorylation. Basal renal IL6 mRNA and phosphorylation of its downstream
      signaling molecule STAT3 were increased as was the product of its action, the
      suppressor of cytokine signaling 3 (SOCS3) mRNA. CONCLUSIONS: Despite known
      unaltered circulating GH levels, remnant kidneys of uremic growth retarded
      juvenile rats show impaired basal signaling along the GH-activated JAK2/STAT5
      signaling pathway. This may well be a consequence of the reduced GHR level and
      the inhibitory effect of the increase in IL-6-mediated SOCS3 expression. This
      renal GH insensitivity, if present in humans, may protect against the potential
      adverse renal effects of GH administration in CKD patients.

PMID- 24463191
TI  - Crystal structure of the external aldimine of Citrobacter freundii methionine
      gamma-lyase with glycine provides insight in mechanisms of two stages of
      physiological reaction and isotope exchange of alpha- and beta-protons of
      competitive inhibitors.
AB  - The three-dimensional structure of the external aldimine of Citrobacter freundii
      methionine gamma-lyase with competitive inhibitor glycine has been determined at
      2.45 A resolution. It revealed subtle conformational changes providing effective
      binding of the inhibitor and facilitating labilization of Calpha-protons of the
      external aldimine. The structure shows that 1, 3-prototropic shift of Calpha
      proton to C4'-atom of the cofactor may proceed with participation of active site
      Lys210 residue whose location is favorable for performing this transformation by
      a concerted mechanism. The observed stereoselectivity of isotopic exchange of
      enantiotopic Calpha-protons of glycine may be explained on the basis of external
      aldimine structure. The exchange of Calpha-pro-(R)-proton of the external
      aldimine might proceed in the course of the concerted transfer of the proton from
      Calpha-atom of glycine to C4'-atom of the cofactor. The exchange of Calpha-pro
      (S)-proton may be performed with participation of Tyr113 residue which should be
      present in its basic form. The isotopic exchange of beta-protons, which is
      observed for amino acids bearing longer side groups, may be effected by two
      catalytic groups: Lys210 in its basic form, and Tyr113 acting as a general acid.

PMID- 24463192
TI  - A study of the native cell wall structures of the marine alga Ventricaria
      ventricosa (Siphonocladales, Chlorophyceae) using atomic force microscopy.
AB  - A substantial proportion of the architecture of the plant cell wall remains
      unknown with a few cell wall models being proposed. Moreover, even less is known
      about the green algal cell wall. Techniques that allow direct visualization of
      the cell wall in as near to its native state are of importance in unravelling the
      spatial arrangement of cell wall structures and hence in the development of cell
      wall models. Atomic force microscopy (AFM) was used to image the native cell wall
      of living cells of Ventricaria ventricosa (V. ventricosa) at high resolution
      under physiological conditions. The cell wall polymers were identified mainly
      qualitatively via their structural appearance. The cellulose microfibrils (CMFs)
      were easily recognizable and the imaging results indicate that the V. ventricosa
      cell wall has a cross-fibrillar structure throughout. We found the native wall to
      be abundant in matrix polysaccharides existing in different curing states. The
      soft phase matrix polysaccharides susceptible by the AFM scanning tip existed as
      a glutinous fibrillar meshwork, possibly incorporating both the pectic- and
      hemicellulosic-type substances. The hard phase matrix producing clearer images,
      revealed coiled fibrillar structures associated with CMFs, sometimes being
      resolved as globular structures by the AFM tip. The coiling fibrillar structures
      were also seen in the images of isolated cell wall fragments. The mucilaginous
      component of the wall was discernible from the gelatinous cell wall matrix as it
      formed microstructural domains over the surface. AFM has been successful in
      imaging the native cell wall and revealing novel findings such as the 'coiling
      fibrillar structures' and cell wall components which have previously not been
      seen, that is, the gelatinous matrix phase. 

PMID- 24463193
TI  - Tooth replacement and putative odontogenic stem cell niches in pharyngeal
      dentition of medaka (Oryzias latipes).
AB  - The small-sized teleost fish medaka, Oryzias latipes, has as many as 1000
      pharyngeal teeth undergoing continuous replacement. In this study, we sought to
      identify the tooth-forming units and determine its replacement cycles, and
      further localize odontogenic stem cell niches in the pharyngeal dentition of
      medaka to gain insights into the mechanisms whereby continuous tooth replacement
      is maintained. Three-dimensional reconstruction of pharyngeal epithelium and
      sequential fluorochrome labeling of pharyngeal bones and teeth indicated that the
      individual functional teeth and their successional teeth were organized in
      families, each comprising up to five generations of teeth and successional tooth
      germs, and that the replacement cycle of functional teeth was approximately 4
      weeks. BrdU label/chase experiments confirmed the existence of clusters of label
      retaining epithelial cells at the posterior end of each tooth family where the
      expression of pluripotency marker Sox2 was confirmed by in situ hybridization.
      Label-retaining cells were also identified in the mesoderm immediately adjacent
      to the posterior end of each tooth family. These data suggest the importance of
      existence of slow-cycling dental epithelial cells and Sox2 expressions at the
      posterior end of each tooth family to maintain continuous tooth formation and
      replacement in the pharyngeal dentition of medaka. 

PMID- 24463194
TI  - An amperometric urea bisosensor based on covalent immobilization of urease on N2
      incorporated diamond nanowire electrode.
AB  - N2 incorporated diamond nanowire (N-DNW) film electrochemical biosensor has
      utilized for the quantitative determination of urea in aqueous solution and urine
      sample. N-DNW electrode is wet-chemically cleaned (oxidation) by boiling in a
      mixture of H2SO4 and HNO3 (3:1) at 200 degrees C for 2h to remove graphite.
      Urease (Urs) and glutamate dehydrogenase (GLDH) are covalently attached to the
      oxidized N-DNW electrode by activating the COOH group of N-DNW using
      ethyl(dimethylaminopropyl)carbodiimide as the coupling agent and N
      hydroxysuccinimide as activator. Fourier transform infrared spectroscopy and X
      ray photoelectron spectroscopy data reveal that carboxylic and hydroxyl
      functionalized nature of N-DNW electrodes Urs-GLDH immobilized N-DNW (Urs-GLDH/N
      DNW) has been successfully utilized in urea biosensor which exhibits good
      performance in sensitivity (6.18 MUA/mg dL/cm(2)), stability (~1 month),
      reproducibility, lower detection limit (3.87 mg/dL) and fast response time
      (>10s). Urs-GLDH/N-DNW also exhibits electrochemical response when tested for
      different concentration of human urine in buffer solution (from 1:9 to 4:6). In
      addition, Urs-GLDH/N-DNW bioelectrode retains 80% of its initial enzyme activity
      for <1 month, when stored at 4-6 degrees C in a refrigerator.

PMID- 24463195
TI  - A colorimetric aptamer biosensor based on cationic polymer and gold nanoparticles
      for the ultrasensitive detection of thrombin.
AB  - A colorimetric assay for the ultrasensitive determination of thrombin based on
      cationic polymer and gold nanoparticles was presented, in which unmodified gold
      nanoparticles (AuNPs) was used as probes and 21-mer thrombin-binding aptamer
      (TBA) as sensing elements. Upon the addition of thrombin, TBA interacted
      specifically with thrombin to form a G-quadruplex structure. As a result, the
      conformation change facilitated the cationic polymer,
      poly(diallyldimethylammonium chloride) (PDDA)-induced AuNP aggregation. Thus, the
      visible change in color from wine-red to blue-purple was readily seen by the
      naked eye. The colorimetric sensor could detect thrombin down to 1 pM with high
      selectivity in the presence of other interferring proteins. Furthermore, the
      assay was successfully employed to determine thrombin in human serum sample,
      which suggested its great potential for diagnostic purposes.

PMID- 24463196
TI  - Sensitive single-color fluorescence "off-on" switch system for dsDNA detection
      based on quantum dots-ruthenium assembling dyads.
AB  - Due to the high importance of detecting DNA with both fast speed and high
      sensitivity, we proposed a new dsDNA detection method relying on a novel single
      color fluorescence "off-on" switch system. Water-soluble glutathione capped CdTe
      QDs (emission at 605 nm) was prepared for taking advantage of the readily tunable
      emission property of QDs. Initially, QDs was completely quenched by the
      Ru(phen)2(dppz)(2+), as the spontaneous formation of QDs-Ru assembling dyads.
      Then, in the case of the addition of dsDNA, the Ru(phen)2(dppz)(2+) was removed
      away from the CdTe QDs, producing free CdTe QDs and the Ru-dsDNA complex. Both of
      them could be excited at the same wavelength and emit overlaid fluorescence. This
      single-color fluorescence "off-on" signal was sensitive to the concentration of
      dsDNA. Native dsDNA with the concentration of 10 pg/mL could be detected when 0.5
      nM CdTe QDs was used, and ssDNA, RNA or BSA had no interference on it. With this
      system, the dsDNA samples of hepatitis B virus (HBV) patients were tested. The
      results were in good agreement with those detected by fluorescence quantitative
      PCR (P>0.05), and for those samples with very low DNA concentrations, this system
      could provide more accurate results, demonstrating the possible clinical
      applicability of this "off-on" switch system. For this system, chemical
      conjugation or labeling of probes is not required, and unmodified native DNA
      targets could be detected in less than half an hour. Therefore, a simple, fast,
      sensitive, low cost, highly selective and practically applicable detection system
      for dsDNA has been described.

PMID- 24463197
TI  - A water-soluble BODIPY derivative as a highly selective "Turn-On" fluorescent
      sensor for H2O2 sensing in vivo.
AB  - A type of BODIPY derivatives was designed and synthesized by the N-alkylation
      reaction of meso-(4-pyridinyl)-substituted BODIPY. The water-solubility of entire
      molecule was improved to a large extent as a result of the formation of cationic
      quaternary ammonium salt, while the strong fluorescence inherent to the BODIPY
      dye fragment is extinguished on alkylation of the pyridine N atom due to the
      photo-induced electron transfer (PET) process. The N-alkylated BODIPY derivative
      4, as a novel water-soluble "Turn-On" fluorescent probe for the discrimination of
      H2O2, was constructed by incorporating 4-(Bromomethyl)benzeneboronic acid pinacol
      ester moiety, which showed highly selective fluorescent response to H2O2 against
      other interferences of ROS and RNS species under physiological conditions, and
      the reaction mechanism of boronate oxidation was confirmed by (1)H NMR, mass
      spectrum and optical spectroscopy analysis. As a biocompatible probe in
      biological systems, probe 4 was successfully applied for monitoring and imaging
      of H2O2 both in vitro and in vivo using HepG2/LO2 cells and angelfish. 

PMID- 24463198
TI  - Interplay of calcium and cadmium in mediating cadmium toxicity.
AB  - The environmentally important toxic metal, cadmium, exists as the Cd(2+) ion in
      biological systems, and in this state structurally resembles Ca(2+). Thus,
      although cadmium exerts a broad range of adverse actions on cells by virtue of
      its propensity to bind to protein thiol groups, it is now well appreciated that
      Cd(2+) participates in a number of Ca(2+)-dependent pathways, attributable to its
      actions as a Ca(2+) mimetic, with a central role for calmodulin, and the
      Ca(2+)/calmodlin-dependent protein kinase II (CaMK-II) that mediates effects on
      cytoskeletal dynamics and apoptotic cell death. Cadmium interacts with receptors
      and ion channels on the cell surface, and with the intracellular estrogen
      receptor where it binds competitively to residues shared by Ca(2+). It increases
      cytosolic [Ca(2+)] through several mechanisms, but also decreases transcript
      levels of some Ca(2+)-transporter genes. It initiates mitochondrial apoptotic
      pathways, and activates calpains, contributing to mitochondria-independent
      apoptosis. However, the recent discovery of the role CaMK-II plays in Cd(2+)
      induced cell death, and subsequent implication of CaMK-II in Cd(2+)-dependent
      alterations of cytoskeletal dynamics, has opened a new area of mechanistic
      cadmium toxicology that is a focus of this review. Calmodulin is necessary for
      induction of apoptosis by several agents, yet induction of apoptosis by Cd(2+) is
      prevented by CaMK-II block, and Ca(2+)-dependent phosphorylation of CaMK-II has
      been linked to increased Cd(2+)-dependent apoptosis. Calmodulin antagonism
      suppresses Cd(2+)-induced phosphorylation of Erk1/2 and the Akt survival pathway.
      The involvement of CaMK-II in the effects of Cd(2+) on cell morphology, and
      particularly the actin cytoskeleton, is profound, favouring actin
      depolymerization, disrupting focal adhesions, and directing phosphorylated FAK
      into a cellular membrane. CaMK-II is also implicated in effects of Cd(2+) on
      microtubules and cadherin junctions. A key question for future cadmium research
      is whether cytoskeletal disruption leads to apoptosis, or rather if apoptosis
      initiates cytoskeletal disruption in the context of Cd(2+). 

PMID- 24463199
TI  - Shikonin time-dependently induced necrosis or apoptosis in gastric cancer cells
      via generation of reactive oxygen species.
AB  - The effects of shikonin on gastric cancer cells were investigated in this study.
      Exposure to shikonin reduced the viability of gastric cancer cells in a time- and
      dose-dependent manner. However, apoptosis was not observed in gastric cancer cell
      treatment with different concentrations of shikonin for 6h. By contrast,
      treatment with shikonin for 24h significantly induced apoptosis, as evidenced by
      the results of TUNEL assay and flow cytometry analysis in proportion to the
      concentration. Disruption of the mitochondrial membrane potential was observed in
      gastric cancer cells that were treated with shikonin for 6 and 24h. Pretreatment
      with necrostatin-1 recovered cell death and mitochondrial membrane potential in
      the 6h shikonin treatment, but not in the 24h shikonin treatment. Western blot
      results reveal enhanced p38 phosphorylation, downregulated AKT phosphorylation,
      and increased caspase3 and PARP cleavage in cells that were treated with shikonin
      for 24h, but not in cells treated for 6h. Shikonin also triggered reactive oxygen
      species (ROS) generation both in the 6 and 24h treatments. Pretreatment with N
      acetylcysteine blocked shikonin-induced cell death. In summary, our findings
      suggest that shikonin, which may function as a promising agent in the treatment
      of gastric cancers, sequentially triggered necrosis or apoptosis through ROS
      generation in gastric cancer cells. 

PMID- 24463202
TI  - Cultural and ethical considerations for cardiopulmonary resuscitation in chinese
      patients with cancer at the end of life.
AB  - End-of-life (EOL) decision making is based on the values and wishes of terminally
      ill patients. However, little is known on the extent to which cultural factors
      affect personal attitudes toward life-sustaining treatments (LSTs) such as
      cardiopulmonary resuscitation (CPR) in China. This study evaluated the cultural
      and ethical considerations during EOL decisions and assessed the factors that
      affect pursuing LSTs in China. We used a case-control study design and compared
      their baseline characteristics with the provided EOL care and treatments. The CPR
      treatment among patients with cancer at EOL was affected by Chinese family
      traditions and Western influences. Our results reflect the need to improve EOL
      care and treatment in China. 

PMID- 24463201
TI  - Potential antioxidant and anxiolytic effects of (+)-limonene epoxide in mice
      after marble-burying test.
AB  - The present study evaluated anxiolytic activity of (+)-limonene epoxide (EL),
      through the marble burying test (MBT) assay, and the antioxidant potential in
      vitro and in vivo in mice hippocampus of adult mice subjected to experimental
      anxiety protocol. For behavioral studies, and in vivo antioxidant analyses, mice
      were treated orally with 0.05% Tween 80 dissolved in 0.9% saline solution
      (vehicle), ascorbic acid 250 mg/kg, diazepam (2 mg/kg) and EL (25, 50 and 75
      mg/kg). Results suggest an anxiolytic effect of (+)-limonene epoxide. A reduction
      in number of buried marbles in groups treated with EL doses of 25, 50 and 75
      mg/kg was observed when compared with diazepam and vehicle groups. This reduction
      was observed after treatments with single and repeated doses, reinforcing the
      hypothesis of anxiolytic effect. The anxiolytic effect was reversed by
      pretreatment with flumazenil (25 mg/kg, o.r) in the same way as it was observed
      with diazepam (2 mg/kg, o.r, positive control), suggesting that these drugs
      possess a similar mechanism of action. In antioxidant tests in vitro, the
      concentrations from 0.9 to 7.2 MUg/ml were tested. The results of in vitro
      antioxidant tests demonstrated a 50% inhibitory effective concentration of
      0.7342, 1.296 and 1.169 MUg/ml against the formation of nitrite ion, hydroxyl
      radical and reactive substances to thiobarbituric acid, respectively. The
      treatment with EL reduced the lipid peroxidation level and nitrite content,
      suggesting an antioxidant role in vivo since it was able to reduce the formation
      of reactive species derived from oxygen and nitrogen. Furthermore, the EL
      increased activity of enzymes catalase and superoxide dismutase in mice
      hippocampus, suggesting that their role may be due to antioxidant upregulation of
      these enzymes.

PMID- 24463203
TI  - Symptoms other than pain in palliative care in Portugal.
AB  - OBJECTIVE: To study the burden of patients' symptoms other than pain and their
      treatment by Portuguese palliative care teams. METHODS: Of the 21 Portuguese
      palliative care teams identified, 10 accepted to participate. Data from all
      patients observed on the 18th week of 2011 were collected. RESULTS: One hundred
      and sixty-four patients were included in this study. One hundred and fifty-one
      patients (92%) had cancer. The patients' median age was 71 years (16-95) and 84
      (51%) were females. The main symptoms were fatigue (116 [85%]) and
      depression/sadness (107 [65%]). Many different drugs were used for symptom
      control and other aims. Symptoms and drugs used here are similar to those
      practiced in other countries. CONCLUSION: The practice of palliative care in
      Portugal seems to be similar to those in other countries.

PMID- 24463204
TI  - In vitro study of beneficial properties and safety of lactic acid bacteria
      isolated from Portuguese fermented meat products.
AB  - Many lactic acid bacteria produce bacteriocins with a rather broad spectrum of
      inhibition, which could offer potential applications in food preservation.
      Bacteriocin production by starter cultures may bring advantage to these strains
      in competitive interactions with pathogenic bacteria from the food matrix. The
      objective of this study was to determine the safety of beneficial strains
      (Lactobacillus plantarum ST202Ch and ST216Ch, Enterococcus faecium ST211Ch, and
      Lactobacillus sakei ST22Ch, ST153Ch and ST154Ch) previously isolated from
      fermented meat products and characterised as bacteriocin producers. Auto
      aggregation was strain-specific, and values of 28.97, 27.86 and 28.56% were
      recorded for L. sakei ST22Ch, ST153Ch and ST154Ch, respectively, 16.95 and 14.58%
      for L. plantarum ST202Ch and ST216Ch, respectively, and 12.77% for E. faecium
      ST211Ch. Various degrees of co-aggregation between 28.85 and 44.76% for Listeria
      monocytogenes 211 and 409, and between 23.60 to 34.96% for E. faecium ATCC 19443
      were observed. According to the results of the diffusion method, the studied
      strains demonstrated susceptibility to penicillin G, ampicillin, amoxicillin,
      amoxicillin/clavulonic acid, imipenem, linezolid, and tetracycline. In addition,
      the susceptibility of the six strains to various non-antibiotic commercial drugs
      was examined. Production of beta-galactosidase by L. sakei ST22Ch, ST153Ch and
      ST154Ch, L. plantarum ST202Ch and ST216Ch, and E. faecium ST211Ch was confirmed
      by employing sterile filter paper discs impregnated with o-nitrophenyl-beta-D
      galactopyranose. A statistically significant (P<0.001) inhibition of
      Mycobacterium tuberculosis growth by bacteriocins produced by L. plantarum
      ST202Ch (38.3%) and ST216Ch (48.6%), L. sakei ST153Ch (16.2%) and ST154Ch
      (16.1%), and E. faecium ST211Ch (21.7%) was observed. As determined by the
      polymerase chain reaction, the tested strains showed a low virulence gene
      profile.

PMID- 24463205
TI  - Prebiotics and probiotics: the prevention and reduction in severity of atopic
      dermatitis in children.
AB  - The purpose of this review was to identify whether supplementation with
      prebiotics and/or probiotics help prevent the development or reduce the severity
      of atopic dermatitis in children less than three years of age. Since 1997,
      immunostimulatory supplements, such as prebiotics and probiotics, have been
      investigated. Various supplementations include probiotics (single strain or mix),
      probiotics with formula, probiotics mix with prebiotics, and prebiotics. In this
      narrative review, we examined 13 key articles on prebiotics and/or probiotics,
      and their effects on infant atopic dermatitis. Among the selected studies, a
      total of 3,023 participants received supplements or placebo. Eight out of the 13
      (61.5%) studies reported a significant effect on the prevention of atopic
      dermatitis after supplementation with probiotics and/or prebiotics. Five out of
      the 13 (38.5%) studies indicated significant reduction in the severity of atopic
      dermatitis after supplementation. Based on the available studies, supplementation
      with certain probiotics (Lactobacillus rhamnosus GG) appears to be an effective
      approach for the prevention and reduction in severity of atopic dermatitis. A mix
      of specific probiotic strains prevented atopic dermatitis among infants. Based on
      studies with prebiotics, there was a long-term reduction in the incidence of
      atopic dermatitis. Supplementation with prebiotics and probiotics appears useful
      for the reduction in the severity of atopic dermatitis. Additional interventional
      studies exploring prebiotics and probiotics are imperative before recommendations
      can be made. 

PMID- 24463206
TI  - Probiotics for human lactational mastitis.
AB  - The use of culture-dependent and -independent techniques to study the human milk
      microbiota and microbiome has revealed a complex ecosystem with a much greater
      diversity than previously anticipated. The potential role of the milk microbiome
      appears to have implications not only for short- and long-term infant health but
      also for mammary health. In fact, mammary disbiosis, which may be triggered by a
      variety of host, microbial and medical factors, often leads to acute, subacute or
      subclinical mastitis, a condition that represents the first medical cause for
      undesired weaning. Multiresistance to antibiotics, together with formation of
      biofilms and mechanisms for evasion of the host immune response, is a common
      feature among the bacterial agents involved. This explains why this condition
      uses to be elusive to antibiotic therapy and why the development of new
      strategies for mastitis management based on probiotics is particularly appealing.
      In fact, selected lactobacilli strains isolated from breast milk have already
      shown a high efficacy for treatment. 

PMID- 24463207
TI  - Probiotic and synbiotic safety in infants under two years of age.
AB  - In this study, we systematically evaluated safety aspects in clinical trials with
      probiotics and synbiotics in young infants (0-2 years of age). This study is an
      update of earlier reports and covers the recent literature from 2008-2013. The
      safety evaluation is performed along the Common Terminology Clinical Adverse
      Events (CTCAE) version 4.0 scale, hereby also providing guidance for future
      studies. Safety aspects are represented and related to number of participants per
      probiotic strain/culture, study duration, dosage, clinical condition and selected
      afflictions. The results show a deficiency in the precise reporting and
      classification of adverse events in most studies. Analysis of 57 clinical trials
      with probiotics and synbiotics in combination with eight follow-up studies
      indicate that probiotic administration to infants between 0 and 24 months is safe
      with regard to the evaluated strains in infants with a particular health status
      or susceptibility. Most adverse events and serious adverse events were considered
      unrelated to the study product, and there were no major safety concerns. Almost
      all studies concluded that none of the adverse effects were related to the study
      product; the study products are generally well tolerated. Finally, inconsistent,
      imprecise and potentially incomplete reporting as well as the variation in
      probiotic strains, dosages, administration regimes, study populations and
      reported outcomes, greatly limit the generalizability of conclusions and argue
      convincingly for obligatory and standardised behaviour on adverse events (CTCAE)
      reporting in 'food' studies. 

PMID- 24463208
TI  - Yoghurt and probiotic bacteria in dietary guidelines of the member states of the
      European Union.
AB  - Beneficial microbes enter the food supply primarily through fermented foods
      (largely milks) and addition of probiotics. Fermented milks are a significant
      component of the diet of some geographical regions, including Europe. The
      fermentation process serves to preserve safety, nutritional quality and
      palatability of milk. In addition, the microbes associated with fermented milks
      and probiotics are associated with human health benefits. However, in the area of
      health claims only one claim for beneficial microbes has been approved in the
      European Union, that is for yoghurt to improve lactose tolerance. We searched for
      health messages that include probiotics or fermented milks in nutrition
      guidelines and recommendations in thirteen countries of the EU plus Switzerland.
      Such messages are allowed when they are made by non-commercial government bodies.
      Our analysis revealed that five EU member states have national nutrition
      guidelines or recommendations that include either probiotics or fermented milks
      with live bacteria. This supports that some EU member states recognise health
      benefits associated with consumption of live microbes, even if commercial
      marketing claims are not authorised. Harmonisation between recommendations and
      approved health-claims would benefit consumers and public health. 

PMID- 24463209
TI  - Meta-analysis: Lactobacillus reuteri strain DSM 17938 (and the original strain
      ATCC 55730) for treating acute gastroenteritis in children.
AB  - Lactobacillus reuteri ATCC 55730 has been shown to provide a moderate clinical
      effect in the treatment of acute gastroenteritis (AGE) in children. However, as
      the L. reuteri ATCC 55730 strain was found to carry potentially transferable
      resistance traits for tetracycline and lincomycin, it was replaced by a new
      strain, L. reuteri DSM 17938, without unwanted plasmid-borne antibiotic
      resistance. Bioequivalence of the two strains has been suggested. We aimed to
      systematically evaluate data on the effectiveness of L. reuteri DSM 17938 and the
      original strain, L. reuteri ATCC 55730, in the treatment of AGE in children. The
      Cochrane Library, MEDLINE, and EMBASE databases, reference lists, and abstract
      books of major scientific meetings were searched in August 2013, with no language
      restrictions, for relevant randomised controlled trials (RCTs). Two RCTs (n=196)
      that evaluated L. reuteri DSM 17938 and three RCTs (n=156) that evaluated L.
      reuteri ATCC 55730, which involved hospitalised children aged 3 to 60 months, met
      the inclusion criteria. Compared with placebo or no treatment, DSM 17938
      significantly reduced the duration of diarrhoea (mean difference -32 h, 95%
      confidence interval (CI): -41 to -24) and increased the chance of cure on day 3
      (relative risk: 3.5, 95% CI: 1.2 to 10.8, random effects model). Similar results
      were obtained with the original strain, L. reuteri ATCC 55730. In conclusion, in
      hospitalised children, use of both strains of L. reuteri reduced the duration of
      diarrhoea, and more children were cured within 3 days. Data from outpatients and
      countryspecific cost-effectiveness analyses are needed. Given the limited data
      and the methodological limitations of the included trials, the evidence should be
      viewed with caution.

PMID- 24463210
TI  - Microgravity control of autophagy modulates osteoclastogenesis.
AB  - Evidence indicates that astronauts experience significant bone loss during space
      mission. Recently, we used the NASA developed rotary cell culture system (RCCS)
      to simulate microgravity (MUXg) conditions and demonstrated increased
      osteoclastogenesis in mouse bone marrow cultures. Autophagy is a cellular
      recycling process of nutrients. Therefore, we hypothesize that MUXg control of
      autophagy modulates osteoclastogenesis. Real-time PCR analysis of total RNA
      isolated from mouse bone marrow derived non-adherent cells subjected to modeled
      MUXg showed a significant increase in autophagic marker Atg5, LC3 and Atg16L mRNA
      expression compared to ground based control (Xg) cultures. Western blot analysis
      of total cell lysates identified an 8.0-fold and 7.0-fold increase in the Atg5
      and LC3-II expression, respectively. Confocal microscopy demonstrated an
      increased autophagosome formation in MUXg subjected RAW 264.7 preosteoclast
      cells. RT(2) profiler PCR array screening for autophagy related genes identified
      that MUXg upregulates intracellular signaling molecules associated with
      autophagy, autophagosome components and inflammatory cytokines/growth factors
      which coregulate autophagy in RAW 264.7 preosteoclast cells. Autophagy inhibitor,
      3-methyladenine (3-MA) treatment of mouse bone marrow derived non-adherent
      mononuclear cells showed a significant decrease in MUXg induced Atg5 and LC3 mRNA
      expression in the presence or absence of RANK ligand (RANKL) stimulation.
      Furthermore, RANKL treatment significantly increased (8-fold) p-CREB
      transcription factor levels under MUXg as compared to Xg cultures and 3-MA
      inhibited RANKL increased p-CREB expression in these cells. Also, 3-MA suppresses
      MUXg elevated osteoclast differentiation in mouse bone marrow cultures. Thus, our
      results suggest that MUXg induced autophagy plays an important role in enhanced
      osteoclast differentiation and could be a potential therapeutic target to prevent
      bone loss in astronauts during space flight missions. 

PMID- 24463211
TI  - The myelodysplastic syndrome-comorbidity index provides additional prognostic
      information on patients stratified according to the revised international
      prognostic scoring system.

PMID- 24463212
TI  - Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with
      thrombopoietin-receptor agonists: a single-center, long-term follow-up.
AB  - Thrombopoietin-receptor agonists increase platelet counts by stimulating the
      thrombopoietin receptor. Bone marrow fibrosis has been reported in patients
      receiving thrombopoietin-receptor agonists. This study determined the extent of
      myelofibrosis, its clinical relevance, and incidence of phenotypic or karyotypic
      abnormalities in patients with immune thrombocytopenia treated with
      thrombopoietin-receptor agonists. The grade of myelofibrosis was assessed before
      (n=15), during (n=117) and after (n=9) treatment in bone marrow biopsies from 66
      patients. The proportion of bone marrow biopsies showing no fibrosis
      (myelofibrosis grade 0) decreased from 67% pre-treatment to 22% at last biopsy,
      of which 59% had grade 1 myelofibrosis and 18% had grade 2 myelofibrosis. The
      median duration of treatment with thrombopoietin-receptor agonists to last bone
      marrow biopsies was 29 months; patients who had two or more biopsies
      significantly more frequently had myelofibrosis grades 2/3 in the last bone
      marrow biopsies as compared to the first. Older age was associated with higher
      grades of fibrosis. No differences in blood counts or lactate dehydrogenase
      levels were found between patients with myelofibrosis grades 0/1 and those with
      grade 2. No clonal karyotypic or immunophenotypic abnormalities emerged. This
      study found that thrombopoietin-receptor agonists induce myelofibrosis grades 2/3
      in approximately one-fifth of patients with immune thrombocytopenia, increasingly
      with >2 years of treatment with thrombopoietin-receptor agonists. Annual/biannual
      follow-up with bone marrow biopsies is, therefore, recommended in patients being
      treated with thrombopoietin-receptor agonists in order to enable prompt
      discontinuation of these drugs should grades 2/3 myelofibrosis develop.
      Discontinuation of thrombopoietin-receptor agonists may prevent development of
      clinical manifestations by stopping progression of fibrosis in grade 2/3.

PMID- 24463213
TI  - The importance of calcium in the regulation of megakaryocyte function.
AB  - Platelet release by megakaryocytes is regulated by a concert of environmental and
      autocrine factors. We previously showed that constitutively released adenosine
      diphosphate by human megakaryocytes leads to platelet production. Here we show
      that adenosine diphosphate elicits, in human megakaryocytes, an increase in
      cytosolic calcium concentration, followed by a plateau, which is lowered in the
      absence of extracellular calcium, suggesting the involvement of Store-Operated
      Calcium Entry. Indeed, we demonstrate that megakaryocytes express the major
      candidates to mediate Store-Operated Calcium Entry, stromal interaction molecule
      1, Orai1 and canonical transient receptor potential 1, which are activated upon
      either pharmacological or physiological depletion of the intracellular calcium
      pool. This mechanism is inhibited by phospholipase C or inositol-3-phosphate
      receptor inhibitors and by a specific calcium entry blocker. Studies on
      megakaryocyte behavior, on extracellular matrix proteins that support proplatelet
      extension, show that calcium mobilization from intracellular stores activates
      signaling cascades that trigger megakaryocyte adhesion and proplatelet formation,
      and promotes extracellular calcium entry which is primarily involved in the
      regulation of the contractile force responsible for megakaryocyte motility. These
      findings provide the first evidence that both calcium mobilization from
      intracellular stores and extracellular calcium entry specifically regulate human
      megakaryocyte functions. 

PMID- 24463214
TI  - In vivo evidence for an instructive role of fms-like tyrosine kinase-3 (FLT3)
      ligand in hematopoietic development.
AB  - Cytokines are essential regulators of hematopoiesis, acting in an instructive or
      permissive way. Fms-like tyrosine kinase 3 ligand (FLT3L) is an important
      cytokine for the development of several hematopoietic populations. Its receptor
      (FLT3) is expressed on both myeloid and lymphoid progenitors and deletion of
      either the receptor or its ligand leads to defective developmental potential of
      hematopoietic progenitors. In vivo administration of FLT3L promotes expansion of
      progenitors with combined myeloid and lymphoid potential. To investigate further
      the role of this cytokine in hematopoietic development, we generated transgenic
      mice expressing high levels of human FLT3L. These transgenic mice displayed a
      dramatic expansion of dendritic and myeloid cells, leading to splenomegaly and
      blood leukocytosis. Bone marrow myeloid and lymphoid progenitors were
      significantly increased in numbers but retained their developmental potential.
      Furthermore, the transgenic mice developed anemia together with a reduction in
      platelet numbers. FLT3L was shown to rapidly reduce the earliest erythroid
      progenitors when injected into wild-type mice, indicating a direct negative role
      of the cytokine on erythropoiesis. We conclude that FLT3L acts on multipotent
      progenitors in an instructive way, inducing their development into
      myeloid/lymphoid lineages while suppressing their megakaryocyte/erythrocyte
      potential. 

PMID- 24463215
TI  - Complex or monosomal karyotype and not blast percentage is associated with poor
      survival in acute myeloid leukemia and myelodysplastic syndrome patients with
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study.
AB  - Acute myeloid leukemia and myelodysplastic syndrome with
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2) have a poor prognosis. Indeed, the
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has been recognized as a poor risk karyotype
      in the revised International Prognostic Scoring System. However,
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is not among the cytogenetic abnormalities
      pathognomonic for diagnosis of acute myeloid leukemia irrespective of blast
      percentage in the 2008 WHO classification. This multicenter study evaluated the
      clinico-pathological features of acute myeloid leukemia/myelodysplastic syndrome
      patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and applied the revised
      International Prognostic Scoring System to myelodysplastic syndrome patients with
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2). A total of 103
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2) patients were reviewed and had a median bone
      marrow blast count of 4% in myelodysplastic syndrome (n=40) and 52% in acute
      myeloid leukemia (n=63) (P<0.001). Ninety-one percent of patients showed
      characteristic dysmegakaryopoiesis. There was no difference in overall survival
      between acute myeloid leukemia and myelodysplastic syndrome patients with
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2) (12.9 vs. 7.9 months; P=0.16). Eighty-three
      percent of patients died (median follow up 7.9 months). Complex karyotype,
      monosomal karyotype and dysgranulopoiesis (but not blast percentage) were
      independent poor prognostic factors in the entire cohort on multivariable
      analysis. The revised International Prognostic Scoring System better reflected
      overall survival of inv(3)(q21q26.2)/t(3;3)(q21;q26.2) than the International
      Prognostic Scoring System but did not fully reflect the generally dismal
      prognosis. Our data support consideration of myelodysplastic syndrome with
      inv(3)(q21q26.2)/t(3;3)(q21;q26.2) as an acute myeloid leukemia with recurrent
      genetic abnormalities, irrespective of blast percentage. 

PMID- 24463216
TI  - HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation.
AB  - Peptide loading of class II MHC molecules in endosomal compartments is regulated
      by HLA-DM. HLA-DO modulates HLA-DM function, with consequences for the spectrum
      of MHC-bound epitopes presented at the cell surface for interaction with T cells.
      Here, we summarize and discuss recent progress in investigating the molecular
      mechanisms of action of HLA-DM and HLA-DO and in understanding their roles in
      immune responses. Key findings are the long-awaited structures of HLA-DM in
      complex with its class II substrate and with HLA-DO, and observation of a novel
      phenotype--autoimmunity combined with immunodeficiency--in mice lacking HLA-DO.
      We also highlight several areas where gaps persist in our knowledge about this
      pair of proteins and their molecular biology and immunobiology.

PMID- 24463217
TI  - Specific targeting of tumor cells by lyophilisomes functionalized with
      antibodies.
AB  - Lyophilisomes are a novel class of proteinaceous biodegradable nano/micro drug
      delivery capsules prepared by freezing, annealing and Iyophilization. In the
      present study, lyophilisomes were functionalized for active targeting by antibody
      conjugation in order to obtain a selective drug-carrier system. Lyophilisomes
      were vapor crosslinked for 2h, resulting in stable capsules, while leaving
      sufficient primary amines for further modification. The humanized KC4 (hKC4)
      antibody was conjugated to lyophilisomes to achieve specific targeting to mucin 1
      (MUC1)-overexpressing tumor cells. For this, thiolated antibodies were conjugated
      to maleimide-activated lyophilisomes, resulting in an hKC4 specific drug
      targeting system toward MUC1-overexpressing human ovarian and cervical tumor
      cells. FACS analysis demonstrated that hKC4-conjugated lyophilisomes bound
      specifically to MUC1-overexpressing tumor cells (HeLa, OVCAR-3, and SKOV-3
      cells), compared to MUC1-negative cells (LS174T). In addition, control non
      specific IgG-conjugated lyophilisomes did not bind to MUC1-overexpressing tumor
      cells. When MUC1-positive and -negative cells were combined in one culture, hKC4
      conjugated lyophilisomes specifically targeted MUC1-positive cells, whereas
      negative cells showed merely background levels. Transmission electron microscopy
      showed uptake of hKC4-conjugated lyophilisomes via phagocytosis or
      macropinocytosis. In conclusion, hKC4-conjugated albumin-based lyophilisomes
      represent a potential drug delivery system for targeted drug transport to MUC1
      overexpressing tumor cells. 

PMID- 24463218
TI  - Synthesis of 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole
      derivatives: their evaluation as potential PDE 4B inhibitors possessing cytotoxic
      properties against cancer cells.
AB  - The 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives
      were designed as potential inhibitors of PDE4B. These compounds were synthesized
      via a multi-step sequence consisting of copper-catalyzed azide-alkyne
      cycloaddition (CuAAC) as a key step in aqueous media. The required alkynes were
      prepared from nimesulide via N-propargylation and then nitro group reduction
      followed by a CAN mediated modified Skraup reaction of the resulting amine. All
      the synthesized compounds showed PDE4B inhibitory properties in vitro at 30MUM
      with two compounds showing >50% inhibition that were supported by the in silico
      docking results of these compounds at the active site of PDE4B. Three of these
      PDE4 inhibitors showed promising cytotoxic properties against A549 human lung
      cancer cells in vitro with IC50 ~8-9MUM. 

PMID- 24463219
TI  - Synthesis, characterization and in vitro anti-neoplastic activity of gypsogenin
      derivatives.
AB  - Gypsogenin (L(1); 3-hydroxy-23-oxoolean-12-en-28-oic acid), a natural saponin,
      was isolated from the boiling water extract of Gypsophila arrostii roots. In
      addition, the derivatives gypsogenin thiosemicarbazone (L(2); 23
      [(aminocarbonothioyl)hydrazono]-3-hydroxolean-12-en-28-oic acid) and gypsogenin
      thiosemicarbazone glyoxime (L(3)H2; (3beta)-3-hydroxy-23-[({[(1Z,2E)-N-hydroxy-2
      (hydroxyimino)ethanimidoyl]amino}carbonothioyl)hydrazono] olean-12-en-28-oic
      acid) as well as the Cu(II) and Co(II) complexes of L(3)H2 were prepared. The
      structures were established on NMR analysis ((1)H, (13)C NMR, HMBC, HMQC, and
      NOESY), FT-IR and completed by analysis of LC/MS. Furthermore, the
      antiproliferative effects of the Co(II) and Cu(II) complexes of the gypsogenin
      derivatives were assayed in human promyelocytic leukemia (HL 60) cells. These
      complexes were found to be potent anticancer agents with concentrations that
      inhibited 50% of proliferation (IpC50) between 5MUM and 40MUM. Cell death was
      distinguished by HO/PI double staining. The Co(II) complex of L(3)H2 has shown
      approximately %50 apoptotic effect at 10MUM concentration. Paclitaxel has been
      used as positive control. 

PMID- 24463220
TI  - Can thoracic impedance monitor the depth of chest compressions during out-of
      hospital cardiopulmonary resuscitation?
AB  - AIM: To analyze the relationship between the depth of the chest compressions and
      the fluctuation caused in the thoracic impedance (TI) signal in out-of-hospital
      cardiac arrest (OHCA). The ultimate goal was to evaluate whether it is possible
      to identify compressions with inadequate depth using information of the TI
      waveform. METHODS: 60 OHCA episodes were extracted, one per patient, containing
      both compression depth (CD) and TI signals. Every 5s the mean value of the maxima
      of the CD, Dmax, and three features characterizing the fluctuations caused by the
      compressions in the TI waveform (peak-to-peak amplitude, area and curve length)
      were computed. The linear relationship between Dmax and the TI features was
      tested using Pearson correlation coefficient (r) and univariate linear regression
      for the whole population, for each patient independently, and for series of
      compressions provided by a single rescuer. The power of the three TI features to
      classify each 5s-epoch as shallow/non-shallow was evaluated in terms of area
      under the curve, sensitivity and specificity. RESULTS: The r was 0.34, 0.36 and
      0.37 for peak-to-peak amplitude, area and curve length respectively when the
      whole population was analyzed. Within patients the median r was 0.40, 0.43 and
      0.47, respectively. The analysis of the series of compressions yielded a median r
      of 0.81 between Dmax and the peak-to-peak amplitude, but it decreased to 0.47
      when all the series were considered jointly. The classifier based on the TI
      features showed 90.0%/37.1% and 86.2%/43.5% sensitivity/specificity values, and
      an area under the curve of 0.75 and 0.71 for the training and test set
      respectively. CONCLUSION: Low linearity between CD and TI was noted in OHCA
      episodes involving multiple rescuers. Our findings suggest that TI is unreliable
      as a predictor of Dmax and inaccurate in detecting shallow compressions.

PMID- 24463221
TI  - Long-term functional outcome of cardiac arrest survivors.

PMID- 24463223
TI  - A randomised control trial of prompt and feedback devices and their impact on
      quality of chest compressions--a simulation study.
AB  - AIM: This study aims to compare the effect of three CPR prompt and feedback
      devices on quality of chest compressions amongst healthcare providers. METHODS: A
      single blinded, randomised controlled trial compared a pressure sensor/metronome
      device (CPREzy), an accelerometer device (Phillips Q-CPR) and simple metronome on
      the quality of chest compressions on a manikin by trained rescuers. The primary
      outcome was compression depth. Secondary outcomes were compression rate,
      proportion of chest compressions with inadequate depth, incomplete release and
      user satisfaction. RESULTS: The pressure sensor device improved compression depth
      (37.24-43.64 mm, p=0.02), the accelerometer device decreased chest compression
      depth (37.38-33.19 mm, p=0.04) whilst the metronome had no effect (39.88 mm vs.
      40.64 mm, p=0.802). Compression rate fell with all devices (pressure sensor
      device 114.68-98.84 min(-1), p=0.001, accelerometer 112.04-102.92 min(-1),
      p=0.072 and metronome 108.24 min(-1) vs. 99.36 min(-1), p=0.009). The pressure
      sensor feedback device reduced the proportion of compressions with inadequate
      depth (0.52 vs. 0.24, p=0.013) whilst the accelerometer device and metronome did
      not have a statistically significant effect. Incomplete release of compressions
      was common, but unaffected by the CPR feedback devices. Users preferred the
      accelerometer and metronome devices over the pressure sensor device. A post hoc
      study showed that de-activating the voice prompt on the accelerometer device
      prevented the deterioration in compression quality seen in the main study.
      CONCLUSION: CPR feedback devices vary in their ability to improve performance. In
      this study the pressure sensor device improved compression depth, whilst the
      accelerometer device reduced it and metronome had no effect.

PMID- 24463222
TI  - Hypertonic saline infusion during resuscitation from out-of-hospital cardiac
      arrest: a matched-pair study from the German Resuscitation Registry.
AB  - AIM: Survival rates after out-of-hospital-cardiac-arrest (OHCA) differ widely
      between EMS systems. Since hypertonic saline appears to improve long-term outcome
      after OHCA, some local EMS systems have included it in their treatment protocols
      for OHCA. Our first aim was to give a quality review of one of these protocols.
      Our second aim was to assess whether short-term survival improves when hypertonic
      saline is used in resuscitation after OHCA. METHODS: Matched pairs were
      identified for the independent "return of spontaneous circulation (ROSC) after
      cardiac arrest" (RACA) score variables and for use of ACD-CPR, adrenaline, and
      amiodarone from the German Resuscitation Registry (GRR) for January 2000 to March
      2011. Patients received either 2mlkg(-1) hypertonic saline with hydroxyethyl
      starch (7.2% NaCl with 6% hydroxyethyl starch 200,000/0.5, HyperHAES(r) [HHS])
      infused intravenously within 10min during CPR according to local treatment
      protocols or standard of care CPR (NON-HHS). The primary endpoint was admission
      to hospital rate (with spontaneous circulation); secondary endpoint was ROSC rate
      in relation to RACA score. RESULTS: 322 matched pairs were defined for 14
      variables. Predicted ROSC-rate using RACA-score was similar in HHS (44.63%) and
      NON-HHS (43.63%; p=0.440). In contrast, 190 (59.0%) HHS patients achieved ROSC
      compared with only 136 NON-HHS patients (42.2%; chi(2): p<0.0001). Short term
      survival measured as rate of "admission to hospital with spontaneous circulation"
      was achieved in 169 HHS patients (52.5%) versus 108 NON-HHS patients (33.5%) (OR
      2.19; 95%CI: 1.592-3.009; chi(2): p<0.0001). CONCLUSION: Locally implemented
      treatment protocols using hypertonic saline/HES after OHCA are safe and
      effective. Also, we verified that short-term survival rates were better in
      patients receiving HHS.

PMID- 24463224
TI  - Miniaturized mechanical chest compressor improves calculated cerebral perfusion
      pressure without compromising intracranial pressure during cardiopulmonary
      resuscitation in a porcine model of cardiac arrest.
AB  - OBJECTIVE: One of the major goals of cardiopulmonary resuscitation (CPR) is to
      provide adequate oxygen delivery to the brain for minimizing cerebral injury
      resulted from cardiac arrest. The optimal chest compression during CPR should
      effectively improve brain perfusion without compromising intracranial pressure
      (ICP). Our previous study has demonstrated that the miniaturized mechanical chest
      compressor improved hemodynamic efficacy and the success of CPR. In the present
      study, we investigated the effects of the miniaturized chest compressor (MCC) on
      calculated cerebral perfusion pressure (CerPP) and ICP. METHODS: Ventricular
      fibrillation was electrically induced and untreated for 7min in 13 male domestic
      pigs weighing 39+/-3kg. The animals were randomized to receive mechanical chest
      compression with the MCC (n=7), or the Thumper device (n=6). CPR was performed
      for 5min before defibrillation attempt by a single 150J shock. At 2.5min of CPR,
      the epinephrine at a dose of 20MUg/kg was administered. Additional epinephrine
      was administered at an interval of 3min thereafter. If resuscitation was not
      successful, CPR was resumed for an additional 2min prior to the next
      defibrillation until successful resuscitation or for a total of 15min. Post
      resuscitated animals were observed for 2h. RESULTS: Significantly greater
      intrathoracic positive and negative pressures during compression and
      decompression phases of CPR were observed with the MCC when compared with the
      Thumper device. The MCC produced significantly greater coronary perfusion
      pressure and end-tidal carbon dioxide. There were no statistically significant
      differences in systolic and mean ICP between the two groups; however, both of the
      measurements were slightly greater in the MCC treated animals. Interestingly, the
      diastolic ICP was significantly lower in the MCC group, which was closely related
      to the significantly lower negative intrathoracic pressure in the animals that
      received the MCC. Most important, systolic, diastolic and mean calculated CerPP
      were all significantly greater in the animals receiving the MCC. CONCLUSIONS: In
      the present study, mechanical chest compression with the MCC significantly
      improved calculated CerPP but did not compromise ICP during CPR. It may provide a
      safe and effective chest compression during CPR. Protocol number: P1205.

PMID- 24463225
TI  - Antenatal steroids: can we optimize the dose?
AB  - PURPOSE OF REVIEW: The beneficial effects of antenatal steroids in women at risk
      of preterm birth are evident. A dose of 24 mg appears sufficient, but there are
      insufficient data to recommend betamethasone or dexamethasone, a single steroid
      dose, the optimal interval between doses and repeated courses, the gestational
      age at which treatment is beneficial and the long-term effects of steroid
      treatment. This review addresses these aspects of antenatal steroid treatment.
      RECENT FINDINGS: Although the 12-h and 24-h dosing intervals are equivalent with
      respect to prevention of respiratory distress syndrome, the former enables the
      completion of treatment in 50% more neonates delivered prematurely. Reducing the
      single steroid dose in patients at risk for premature birth reduces the
      associated maternal side effects. An inverse relationship has been demonstrated
      between the number of corticosteroid courses and foetal growth. The reduced size
      of exposed foetuses has been attributed to birth at earlier gestational ages and
      decreased foetal growth. Evidence suggests that antenatal exposure to synthetic
      glucocorticoids in term-born children has long-lasting effects, which may have
      important implications in the recommendation of steroids before elective
      caesarean at term. SUMMARY: The short-term and long-term effects of the dosage
      regimen on the pregnant mother and foetus remain unclear.

PMID- 24463226
TI  - Self-choice enhances value in reward-seeking in primates.
AB  - When an individual chooses one item from two or more alternatives, they compare
      the values of the expected outcomes. The outcome value can be determined by the
      associated reward amount, the probability of reward, and the workload required to
      earn the reward. Rational choice theory states that choices are made to maximize
      rewards over time, and that the same outcome values lead to an equal likelihood
      of choices. However, the theory does not distinguish between conditions with the
      same reward value, even when acquired under different circumstances, and does not
      always accurately describe real behavior. We have found that allowing a monkey to
      choose a reward schedule endows the schedule with extra value when compared to
      performance in an identical schedule that is chosen by another agent (a computer
      here). This behavior is not consistent with pure rational choice theory.
      Theoretical analysis using a modified temporal-difference learning model showed
      an enhanced schedule state value by self-choice. These results suggest that an
      increased reward value underlies the improved performances by self-choice during
      reward-seeking behavior. 

PMID- 24463227
TI  - Amphiregulin.
AB  - Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR), a
      widely expressed transmembrane tyrosine kinase. AREG is synthesized as a membrane
      anchored precursor protein that can engage in juxtacrine signaling on adjacent
      cells. Alternatively, after proteolytic processing by cell membrane proteases,
      mainly TACE/ADAM17, AREG is secreted and behaves as an autocrine or paracrine
      factor. AREG gene expression and release is induced by a plethora of stimuli
      including inflammatory lipids, cytokines, hormones, growth factors and
      xenobiotics. Through EGFR binding AREG activates major intracellular signaling
      cascades governing cell survival, proliferation and motility. Physiologically,
      AREG plays an important role in the development and maturation of mammary glands,
      bone tissue and oocytes. Chronic elevation of AREG expression is increasingly
      associated with different pathological conditions, mostly of inflammatory and/or
      neoplastic nature. Here we review the essential aspects of AREG structure,
      function and regulation, discuss the basis for its differential role within the
      EGFR family of ligands, and identify emerging aspects in AREG research with
      translational potential. 

PMID- 24463228
TI  - Comparative efficacy and safety of mizoribine with mycophenolate mofetil for
      Asian renal transplantation--a meta-analysis.
AB  - OBJECTIVES: Mizoribine (MZR) with its high safety and low cost has been widely
      used in Asia. It has been questioned whether high or low dose of MZR could obtain
      the efficacy and safety similar to mycophenolate mofetil (MMF) following renal
      transplantation. This meta-analysis was done to compare the efficacy and safety
      of high- or low-dose MZR with MMF for immunosuppressive therapy in renal
      transplantation. DESIGN AND METHODS: Available data comparing MZR with MMF in
      renal transplant recipients were searched. Subgroup analysis was conducted
      according to the administration dosage of MZR. Trials were pooled using Meta
      analysis software and confidence intervals were set at 95%. RESULTS: Altogether
      1149 Asian patients from 7 RCTs and 9 cohort studies were included. The efficacy
      of different MZR doses put on par with MMF, but the safety was better than MMF.
      Specifically, recipients taking MZR favor significantly fewer episodes of
      leucocytopenia [RR 0.40 (0.26, 0.60)], gastrointestinal disorder [RR 0.54 (0.40,
      0.73)], CMV infection [RR 0.47 (0.34, 0.64)] and more favorable outcome of
      hepatic dysfunction, although the difference failed to reach a statistical
      significance [RR 0.67 (0.44, 1.00)]. Unfortunately, hyperuricemia was
      significantly obvious in MZR group [RR 1.96 (1.47, 2.61)]. CONCLUSIONS: MZR is an
      effective and safe immunosuppressive agent and high-dose MZR can be recommended
      as an alternative to MMF following adult renal transplantation in Asia, but
      hyperuricemia and liver damage should be closely monitored during the medication
      period.

PMID- 24463229
TI  - Development of an improved time-resolved fluoroimmunoassay for simultaneous
      quantification of C-peptide and insulin in human serum.
AB  - OBJECTIVES: Diabetes mellitus is a chronic disease affecting millions of people
      globally and resulting in significant death rates each year. A fast, inexpensive
      alternative to traditional testing and monitoring techniques is desirable, since
      secretion of insulin and C-peptide is impaired in diabetes mellitus. DESIGN AND
      METHODS: A highly sensitive immunoassay was developed for the simultaneous
      measurement of C-peptide and insulin levels in human serum, utilizing dual-label
      time-resolved fluoroimmunoassay (TRFIA) and magnetic particle technologies. This
      assay was characteristic for a single-step sandwich-type immunoassay, wherein
      antibody-coated magnetic particles were used as the solid phase and Eu(3+) and
      Sm(3+) chelate labels were used for detection. RESULTS: Antibody-coated magnetic
      particles in a TRFIA format performed well in addressing a number of quantitative
      needs. CONCLUSIONS: The results of this assay correlated well with commercial
      chemiluminescence assays and provided a number a advantages, including reduced
      sample volume, reduced reagent and personnel costs and reduced assay time, while
      maintaining the required clinical sensitivity.

PMID- 24463230
TI  - The shift from fluoride/oxalate to acid citrate/fluoride blood collection tubes
      for glucose testing - the impact upon patient results.
AB  - OBJECTIVES: To ascertain whether or not the change in blood collection tubes for
      plasma glucose from fluoride/oxalate to citrate/fluoride/EDTA has had an effect
      upon the glucose results. METHODS: Plasma glucose results from fasting patients
      from 2007 to 2012 were extracted from the laboratory information system. The data
      was evaluated in order to see the potential impact on patient results due to the
      change in glucose stabilizer implemented in September 2010. RESULTS: The mean
      glucose result was increased by approximately 14% (difference: +0.80mmol/L) after
      the implementation of the citrate-buffered tubes (mean value=6.45mmol/L; n=15125)
      as compared to fluoride/oxalate tubes (mean value=5.65mmol/L; n=15867).
      CONCLUSIONS: An increase in glucose results is seen after changing to citrate
      buffered tubes due to the improved stabilizing effect as compared to fluoride.
      Properly collected blood samples will lead to the patient being correctly
      diagnosed. However, decision limits and reference intervals for glucose may need
      to be revised using citrate-tubes.

PMID- 24463231
TI  - Lokomat: a therapeutic chance for patients with chronic hemiplegia.
AB  - BACKGROUND: Treadmill training with partial body weight support has been
      suggested as a useful strategy for gait rehabilitation after stroke. OBJECTIVES:
      This prospective, randomized, controlled study of gait training tested the
      feasibility and potential efficacy of using a robotic-assisted gait device,
      Lokomat, for treadmill training with partial body weight support in subjects with
      chronic hemiplegia; the device was also compared with conventional home exercise.
      METHODS: Twenty-two male ambulatory ischemic or hemorrhagic induced stroke
      patients with chronic hemiplegia lasting at least 12 months were enrolled in this
      prospective study. The patients were assigned to either the Lokomat group or the
      conventional exercise group. The Lokomat group underwent active robotic training
      for ten sessions (five sessions per week for two weeks). Each session lasted 30
      minutes. If a patient missed three consecutive training sessions, he was removed
      from the study. The Timed Up and Go Test is used to assess mobility and requires
      both static and dynamic balance. The 10-m Timed Walking Speed Test is designed to
      determine the patient's overground walking speed. The Mini-Mental State
      Examination and Hospital Anxiety and Depression Scale were used for mental and
      psychological evaluation; the Functional Ambulation Categories was used to assess
      ambulatory status. RESULTS: Within each eight-week interval, the patients
      undergoing the Lokomat training demonstrated significantly greater improvement on
      the Timed Up and Go Test and 10-m Timed Walking Speed Test than those undergoing
      conventional training. CONCLUSION: Despite the small number of patients in the
      study, the present data suggests that the robotic-assisted device, Lokomat,
      provides innovative possibilities for gait training in chronic hemiplegia
      rehabilitation by training at higher intensity levels for longer durations than
      traditional home exercise.

PMID- 24463232
TI  - Cognitive dysfunction and functional limitations are associated with major
      depression in stroke survivors attending rehabilitation in Nigeria.
AB  - BACKGROUND: The frequency and predictors of post-stroke depression diagnosed
      according to codified criteria remain unknown in Nigeria. OBJECTIVES: We report
      on the predictors of post-stroke major depressive disorder (MDD) in Nigeria using
      standardized assessment methods. METHOD: Using a case-control design, we
      consecutively recruited 260 participants. Among them were 130 stroke survivors
      attending rehabilitation. Along with historical details, an exploration for MDD
      meeting criteria in the fourth edition of the Diagnostic and Statistical Manual
      of Mental Disorders was carried out using a semi-structured interview. Cognition
      was assessed using both the Mini Mental State Examination and the modified
      Indiana University Token test, while disability was assessed using the modified
      Rankin Scale. Associations were explored using univariate and multivariate
      analyses. RESULTS: The diagnosis of MDD was more frequently present in the stroke
      survivors (41.5%, p < 0.001). It was strongly associated with female gender (p <
      0.001, O.R = 3.77, 95% C.I = 1.78-8.00), disability (p = 0.001, O.R = 3.27, 95%
      C.I = 1.57-6.83), and cognitive dysfunction (p < 0.001, O.R = 5.28, 95% C.I =
      2.25-12.41). Female gender (p = 0.037, O.R = 2.65, 95% C.I = 1.06-6.62) and
      cognitive dysfunction (P = 0.03, O.R = 4.58, 95% C.I = 1.68-12.46) were
      independent predictors of post-stroke MDD. CONCLUSION: Post stroke MDD is common
      in Nigerian survivors attending rehabilitation. The high rates reported in this
      population may be the result of factors affecting the efficient management of
      stroke in developing countries.

PMID- 24463233
TI  - Effectiveness of eccentric viewing training for daily visual activities for
      individuals with age-related macular degeneration: a systematic review and meta
      analysis.
AB  - BACKGROUND: Eccentric viewing training can be successfully applied in the
      clinical setting based on positive evidence. Nonetheless, published research
      should be integrated to provide a conclusive perspective of the efficacy of
      eccentric viewing training. OBJECTIVE: Meta-analysis was conducted to examine
      effectiveness of eccentric viewing training on daily visual activities for
      individuals with age-related macular degeneration (AMD). METHODS: The papers used
      in this study were located through PubMed, Ovid, ProQuest, EBSCOhost, RISS, and
      KMbase on studies published between January, 1990 and December, 2012. The
      keywords for searching were "age-related macular degeneration" and "eccentric
      viewing", "eccentric fixation", "peripheral vision" or "preferred retinal loci".
      The effect sizes were calculated using Comprehensive Meta-Analysis 2.0 and
      interpreted according to Cohen's criteria. RESULTS: A total of 258 studies were
      found, among which five papers suited the main selection criteria for final
      analysis. The entire effect size was 0.660 (95% CI, 0.232 ~ 1.088), indicating a
      moderate effect size of the eccentric viewing training for individuals with AMD
      in their daily visual activities (p < 0.05). CONCLUSIONS: The results of this
      study demonstrated the clinical effectiveness of eccentric viewing training for
      individuals with AMD. This result should be interpreted cautiously, though, given
      the possibility of publication bias.

PMID- 24463234
TI  - Spinal cord injury secondary to front rolls as part of military physical
      training: a case report.
AB  - OBJECTIVE: To report an unusual case of cervical spinal cord injury. STUDY
      DESIGN: Case report of a 23 year old soldier who sustained spinal cord injury in
      front rolls during a military training program. SETTINGS: Spinal Cord Injuries
      Unit, Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi,
      Pakistan. CASE REPORT: A 23 year old soldier, who voluntarily joined a military
      training program, suffered spinal cord injury in doing front rolls resulting in
      tetraplegia and incontinence for bowel and bladder corresponding to the injury
      level of C5 ASIA Impairment Scale C with Functional Independence Measure Score of
      40/126. His Magnetic Resonance Imaging showed posterior displacement of CV3
      resulting in cord compression and swelling at CV3 and CV4 levels. He was managed
      conservatively by comprehensive rehabilitation and improved to spinal cord injury
      C5 ASIA Impairment Scale D with Functional Independence Measure Score of 76/126.
      CONCLUSION: This case report describes spinal cord injury secondary to front
      rolls. As front-rolls are part and parcel of military training, awareness and
      coaching to ensure safety must be exercised from the beginning of any training
      program.

PMID- 24463235
TI  - Transitions between SNF and home-based care in patients with multiple sclerosis.
AB  - OBJECTIVES: To assess patient characteristics and risk factors associated with
      care transitions between skilled nursing facility (SNF) and home care for
      patients with multiple sclerosis (MS) in an effort to improve outcomes and
      optimize patient care pathways. BACKGROUND: MS is a chronic neurologic illness of
      younger adults that is associated with physical disability, cognitive impairment
      and a high need for supportive services. METHODS: The study was based on the 2005
      Nursing Home Minimum Data Set and the Outcome and Assessment Information Set data
      (n = 10,064). We performed multivariate evaluation of patient risk factors for
      skilled nursing facility (SNF) admission and disposition while controlling for
      potential patient self-selection and other characteristics that affect care
      utilization. RESULTS: MS patients with recent history of home care use were less
      likely to be admitted to an acute care hospital and had higher physical
      disability at SNF admission than SNF patients who did not use home care.
      Insurance type (Medicaid) and availability of informal caregivers were associated
      with the use of homecare services after a SNF stay, while patient demographic and
      clinical characteristics did not explain SNF disposition. CONCLUSIONS: Future
      studies should explore the association between the local availability and
      affordability of home-based services and physician attitude about community-based
      care management of disabled patients.

PMID- 24463236
TI  - Effects of a resistance training program and subsequent detraining on muscle
      strength and muscle power in multiple sclerosis patients.
AB  - BACKGROUND: Although resistance training adaptations in multiple sclerosis (MS)
      patients have been described, the detraining response in this population is
      largely unknown. OBJECTIVE: [corrected] This study was designed to evaluate the
      effects of a 12-week detraining period on muscle strength (isometric and
      endurance) and muscle power of multiple sclerosis (MS) patients that had
      previously carried out a 12-week resistance training program (RTP). METHODS:
      Forty-two MS patients were randomly assigned into two groups: an exercise group
      (EG) that performed a 12-week RTP for the knee extensors muscles; and a control
      group (CG), that did not perform any specific training. Knee extension maximal
      voluntary isometric contraction (MVIC), muscle power and muscle endurance were
      evaluated before and after the RTP, as well as 12 weeks after training
      completion. A strain gauge was used to measure the maximal voluntary isometric
      contraction and muscle power was assessed with a linear encoder. Muscle endurance
      was interpreted as the number of repetitions that a patient could perform in a
      single set of knee extension exercise. RESULTS: The EG increased MVIC and muscle
      power after the training period, although the training did not affect muscle
      endurance. After 12 weeks of detraining, MVIC returned to pre-training values but
      muscle power was still greater than pre-training values in the EG. The CG did not
      present any change in the variables measured during the intervention.
      CONCLUSIONS: A 12-week RTP improved MVIC and muscle power in MS patients.
      Additionally, 12 weeks of detraining blunted strength training adaptations in MS
      patients, although muscle power training adaptations were still evident after the
      detraining period.

PMID- 24463237
TI  - Discrimination of three dimensional fluorescence spectra based on wavelet
      analysis and independent component analysis.
AB  - Fluorescence spectroscopy is a rapid and non-destructive method for monitoring
      water quality. In this work, wavelet analysis, together with independent
      component analysis (ICA), was applied for component recognition of seriously
      overlapped, multi-component, three dimensional fluorescence spectra. Wavelet
      analysis extracts the features of the spectra and amplifies differences among
      phenolic homologs. ICA analysis in blind signal separation was used to separate
      single component before multiple linear regression (MLR). The proposed method
      increases the correct classification rate and enriches the spectra library. As
      such, it is a useful alternative to traditional techniques in component
      recognition. 

PMID- 24463238
TI  - Li(+)-molecule interactions of lithium tetrafluoroborate in propylene carbonate +
      N,N-dimethylformamide mixtures: an FTIR spectroscopic study.
AB  - FTIR (Fourier transformed infrared) spectra have been collected and analyzed for
      solutions of lithium tetrafluoroborate in propylene carbonate (PC), N,N
      dimethylformamide (DMF), and PC+DMF mixtures. The band splitting and symmetric
      ring deformation for PC and O=C-N deformation for DMF suggest that there is a
      strong interaction between lithium cations and solvent molecules. The solvent
      molecules have been assigned to two types, the free and complexed molecules. By a
      comparison of the intensity for the corresponding bands, it has been concluded
      that Li(+) cations are preferentially solvated by DMF molecules in the
      LiBF4/PC+DMF solutions. This has been explained by the difference in values of
      donor number (DN).

PMID- 24463239
TI  - Binding of helicid to human serum albumin: a hybrid spectroscopic approach and
      conformational study.
AB  - The interaction between human serum albumin and helicid was studied by steady
      state fluorescence, ultraviolet-visible, circular dichroism, Fourier transform
      infrared techniques and molecular modeling. The binding site numbers, association
      constants, and corresponding thermodynamic parameters were used to investigate
      the quenching mechanism. The alternations of protein secondary structure in the
      presence of helicid were demonstrated using synchronous fluorescence, Fourier
      transform infrared, circular dichroism and three-dimensional fluorescence
      spectra. The molecular modeling results revealed that helicid could bind to
      hydrophobic pocket of HSA with hydrophobic and hydrogen bond force. The binding
      site of helicid in HSA was ascertained. Moreover, an apparent distance of 3.33 nm
      between the Trp214 and helicid was obtained via fluorescence resonance energy
      transfer method.

PMID- 24463240
TI  - A highly selective chemosensor for Al3+ based on 2-oxo-quinoline-3-carbaldehyde
      Schiff-base.
AB  - A new Schiff-base ligand (1) with good fluorescence response to Al(3+), derived
      from 2-oxo-quinoline-3-carbaldehyde and nicotinic hydrazide, had been synthesized
      and investigated in this paper. Spectroscopic investigation revealed that the
      compound 1 exhibited a high selectivity and sensitivity toward Al(III) ions over
      other commonly coexisting metal ions in ethanol, and the detection limit of
      Al(3+) ions is at the parts per billion level. The mass spectra and Job's plot
      confirmed the 1:1 stoichiometry between 1 and Al(3+). Potential utilization of 1
      as intracellular sensors of Al(3+) ions in human cancer (HeLa) cells was also
      examined by confocal fluorescence microscopy. 

PMID- 24463241
TI  - Spectral-luminescent properties of laurdan molecule.
AB  - Quantum-chemical calculations of ground and excited states of fluorescent probe
      (laurdan) by ab initio and semiempirical methods were performed. The laurdan
      optimized geometries of S0 and S1 states were obtained. The influence of laurdan
      nonrigidity structure on dipole moments and location of energy levels were
      studied. The specific solvation centers of laurdan were obtained. The rate
      constants of photoprocesses and fluorescence quantum yield of laurdan in non
      polar solvent were calculated. 

PMID- 24463242
TI  - Adsorption of Acid Red 57 from aqueous solutions onto polyacrylonitrile/activated
      carbon composite.
AB  - The adsorption of Acid Red 57 (AR57) onto Polyacrylonitrile/activated carbon
      (PAN/AC) composite was investigated in aqueous solution in a batch system with
      respect to contact time, pH and temperature. Physical characteristics of (PAN/AC)
      composite such as fourier transform infrared (FTIR) spectroscopy and scanning
      electron microscopy (SEM) were obtained. Langmuir and Freundlich adsorption
      models were applied to describe the equilibrium isotherms and the isotherm
      constants were determined. The activation energy of adsorption was also evaluated
      for the adsorption of AR57 onto (PAN/AC) composite. The pseudo-first-order and
      pseudo-second-order kinetic models were used to describe the kinetic data. The
      dynamic data fitted the pseudo-second-order kinetic model well. The activation
      energy, change of free energy, enthalpy and entropy of adsorption were also
      evaluated for the adsorption of AR57 onto (PAN/AC) composite. The thermodynamics
      of the adsorption indicated spontaneous and exothermic nature of the process. The
      results indicate that (PAN/AC) composite could be employed as low-cost material
      for the removal of acid dyes from textile effluents. 

PMID- 24463243
TI  - Spectroscopic and molecular modeling methods to investigate the interaction
      between 5-Hydroxymethyl-2-furfural and calf thymus DNA using ethidium bromide as
      a probe.
AB  - In this work, the interaction of 5-Hydroxymethyl-2-furfural (5-HMF) with calf
      thymus DNA (ctDNA) under simulated physiological conditions (Tris-HCl buffer of
      pH 7.40), was explored by UV absorption spectroscopy, fluorescence spectroscopy
      and molecular modeling method, using ethidium bromide (EB) as a fluorescence
      probe of DNA. The fluorescence quenching mechanism of EB-ctDNA by 5-HMF was
      confirmed to be a static quenching, which derived from the formation of a new
      complex. The binding constants of 5-HMF with DNA in the presence of EB were
      calculated to be 2.17*10(3), 4.24*10(3) and 6.95*10(3) L mol(-1) at 300, 305 and
      310 K, respectively. The calculated thermodynamic parameters, enthalpy change
      DeltaH and entropy change DeltaS, suggested that both hydrophobic interactions
      and hydrogen bonds played a predominant role in the binding of 5-HMF to DNA.
      According to the UV absorption spectroscopy and melting temperature (Tm) curve
      results, the binding mode of 5-HMF with DNA was indicative of a non-intercalative
      binding, which was supposed to be a groove binding. The molecular modeling
      results showed that 5-HMF could bind into the hydrophobic region of ctDNA and
      supported the conclusions obtained from the above experiments.

PMID- 24463244
TI  - Investigation of interaction of antibacterial drug sulfamethoxazole with human
      serum albumin by molecular modeling and multi-spectroscopic method.
AB  - Interaction of sulfamethoxazole (SMX) with human serum albumin (HSA) was
      investigated by molecular modeling and multi-spectroscopic methods under
      physiological conditions. The interaction mechanism was firstly predicted through
      molecular modeling that confirmed the interaction between SMX and HSA. The
      binding parameters and the thermodynamic parameters at different temperatures for
      the reaction had been calculated according to the Stern-Volmer, Hill, Scatchard
      and the Van't Hoff equations, respectively. One independent class of binding site
      existed during the interaction between HSA and SMX. The binding constants
      decreased with the increasing temperatures, which meant that the quenching
      mechanism was a static quenching. The thermodynamic parameters of the reaction,
      namely standard enthalpy DeltaH(0) and entropy DeltaS(0), had been calculated to
      be -16.40 kJ mol(-1) and 32.33 J mol(-1) K(-1), respectively, which suggested
      that the binding process was exothermic, enthalpy driven and spontaneous. SMX
      bound to HSA was mainly based on electrostatic interaction, but hydrophobic
      interactions and hydrogen bonds could not be excluded from the binding. The
      conformational changes of HSA in the presence of SMX were confirmed by the three
      dimensional fluorescence spectroscopy, UV-vis absorption spectroscopy and
      circular dichroism (CD) spectroscopy. CD data suggested that the protein
      conformation was altered with the reduction of alpha-helices from 55.37% to
      41.97% at molar ratio of SMX/HSA of 4:1.

PMID- 24463245
TI  - Asymmetric 1,3,4-oxadiazole derivatives containing naphthalene and stilbene
      units: synthesis, optical and electrochemical properties.
AB  - Six novel asymmetric 1,3,4-oxadiazole derivatives containing naphthalene and
      stilbene units have been efficiently synthesized and characterized by FT-IR, (1)H
      NMR, (13)C NMR, mass spectrometry and elemental analysis. The UV-vis absorption
      maximum wavelength, fluorescence excitation wavelength, fluorescence emission
      wavelength and fluorescence quantum yield were measured in dilute tetrahydrofuran
      solution. The solvent effect was also studied. The HOMO and LUMO levels of these
      compounds were calculated by density functional theory (DFT) (B3LYP, 6-31G(*))
      method and cyclic voltammetry. They emit bright violet to blue emission with high
      fluorescence quantum yields (0.23-0.94) and large Stokes shifts (53-102 nm).
      These compounds possess high HOMO levels (-5.03 to -5.17 eV) and suitable band
      gaps, indicating that they could be benefit for hole injection. The results show
      that they have a potential for application in optoelectronic materials.

PMID- 24463246
TI  - Colorimetric fluorescent cyanide chemodosimeter based on triphenylimidazole
      derivative.
AB  - In this paper, we demonstrated a highly selective colorimetric chemodosimeter for
      cyanide anion detection. This chemodosimeter having a triphenylimidazole group as
      a fluorescent signal unit and a dicyano-vinyl group as a reaction unit was
      synthesized by the Knoevenagel condensation of 4-(4,5-diphenyl-1H-imidazol-2
      yl)benzaldehyde with malononitrile in a reasonable yield. The probe exhibited an
      intramolecular charge transfer (ICT) absorption band at 420 nm and emission band
      at 620 nm, respectively. Upon the addition of cyanide anion, the probe displayed
      a blue-shifted spectrum and loss in color due to the disruption of conjugation.
      With the aid of the fluorescence spectrometer, the chemodosimeter exhibited a
      detection limit of 0.11 MUM (S/N=3). Interferences from other common anions
      associated with cyanide anion analysis were effectively inhibited.

PMID- 24463247
TI  - Voltage-gated proton channel HV1 in microglia.
AB  - Microglia are brain resident immune cells and their functions are implicated in
      both the normal and diseased brain. Microglia express a plethora of ion channels,
      including K(+) channels, Na(+) channels, TRP channels, Cl(-) channels, and proton
      channels. These ion channels play critical roles in microglial proliferation,
      migration, and production/release of cytokines, chemokines, and neurotoxic or
      neurotrophic substances. Among microglial ion channels, the voltage-gated proton
      channel HV1 is a recently cloned ion channel that rapidly removes protons from
      depolarized cytoplasm and is highly expressed in the immune system. However, the
      function of microglial HV1 in the brain is poorly understood. Recent studies
      showed that HV1 is selectively expressed in microglia but not neurons in the
      brain. At the cellular level, microglial HV1 regulates intracellular pH and aids
      in NADPH oxidase-dependent generation of reactive oxygen species. In a mouse
      model of middle cerebral artery occlusion, microglial HV1 contributes to neuronal
      cell death and ischemic brain damage. This review discusses the discovery,
      properties, regulation, and pathophysiology of microglial HV1 proton channel in
      the brain. 

PMID- 24463249
TI  - Biomonitoring of pesticides by pine needles--chemical scoring, risk of exposure,
      levels and trends.
AB  - Vegetation is a useful matrix for the quantification of atmospheric pollutants
      such as semi-volatile organic compounds (SVOCs). In particular, pine needles
      stand out as effective biomonitors due to the excellent uptake properties of
      their waxy layer. Having previously validated an original and reliable method to
      analyse pesticides in pine needles, our work team set the objective of this study
      to determine the levels of 18 pesticides in Pinus pinea needles collected in 12
      different sampling sites in Portugal. These compounds were selected among a total
      of 70 pesticides by previous chemical scoring, developed to assess their
      probability to occur in the atmosphere. The risk of exposure was evaluated by the
      binomial chemical score/frequency of occurrence in the analysed samples. Levels
      and trends of the chemical families and target of the pesticides were obtained
      regarding the type of land occupation of the selected sites, including the use of
      advanced statistics (principal component analysis, PCA). Finally, some
      correlations with several characteristics of the sampling sites (population,
      energy consumption, meteorology, etc.) were also investigated. 

PMID- 24463248
TI  - Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the
      prostate-specific antigen era.
AB  - BACKGROUND: The role of lycopene in prostate cancer prevention remains
      controversial. We examined the associations between dietary lycopene intake and
      prostate cancer, paying particular attention to the influence of prostate
      specific antigen screening, and evaluated tissue biomarkers in prostate cancers
      in relation to lycopene intake. METHODS: Among 49898 male health professionals,
      we obtained dietary information through questionnaires and ascertained total and
      lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression
      was used to estimate multivariable hazard ratios (HRs) and 95% confidence
      intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess
      tumor biomarker expression in a subset of men. Two-sided chi(2) tests were used
      to calculate the P values. RESULTS: Higher lycopene intake was inversely
      associated with total prostate cancer and more strongly with lethal prostate
      cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P(trend) =
      .04). In a restricted population of screened participants, the inverse
      associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95%
      CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary
      lycopene, early intake, but not recent intake, was inversely associated with
      prostate cancer. Higher lycopene intake was associated with biomarkers in the
      cancer indicative of less angiogenic potential. CONCLUSIONS: Dietary intake of
      lycopene was associated with reduced risk of lethal prostate cancer and with a
      lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong
      progression factor, an endpoint of lethal prostate cancer may be more relevant
      than an endpoint of indolent prostate cancer for lycopene in the era of highly
      prevalent prostate-specific antigen screening.

PMID- 24463250
TI  - Persistent organic pollutant levels in semi-domesticated reindeer (Rangifer
      tarandus tarandus L.), feed, lichen, blood, milk, placenta, foetus and calf.
AB  - A study concerning persistent organic pollutants in Finnish semi-domesticated
      reindeer was conducted in northern Finland. The aim of this study was to explore
      POP presence in different tissues of reindeer. In addition, it was studied how
      POPs are transported from food concentrates and lichen to reindeer hind tissues
      and further to the placenta, foetus, milk and calf. Concentrations of 17
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), 37
      polychlorinated biphenyls (PCBs) (including 12 dioxin-like PCBs), and 15
      polybrominated diphenyl ethers (PBDEs) were analysed. In most of the reindeer
      muscle tissue samples PCBs were clearly dominating compounds (on average 58% of
      the total WHO-TEQ). The total WHO-TEQ was higher in the muscle tissue of reindeer
      calves than in their corresponding hinds (on average 1.7 pg/g fat vs. 1.1 pg/g
      fat, respectively). The total WHO-TEQ concentrations were higher in the muscle
      and liver tissues of reindeer hinds than in their blood or placentas. The
      foetuses had clearly lower WHO-TEQ concentrations than their corresponding hinds.
      The contribution of WHO-PCDD/F-TEQ to the total WHO-TEQ was somewhat higher in
      the liver than in the muscle tissue. The reindeer hind-calf pair, which had gone
      through the lichen diet, had on average higher WHO-PCDD/F- and PCB-TEQ
      concentrations in their tissues than the hind-calf-pair that had gone through the
      reindeer food concentrate diet. WHO-PCB-TEQs in the reindeer foetuses were equal
      with the concentrations of placentas. The reindeer foetuses contained generally
      more PBDEs than their corresponding hinds and placentas. This may indicate
      effective transport of these compounds through the placenta of reindeer.

PMID- 24463251
TI  - Pesticide Toxicity Index--a tool for assessing potential toxicity of pesticide
      mixtures to freshwater aquatic organisms.
AB  - Pesticide mixtures are common in streams with agricultural or urban influence in
      the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess
      potential aquatic toxicity of complex pesticide mixtures by combining measures of
      pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is
      determined separately for fish, cladocerans, and benthic invertebrates. This
      study expands the number of pesticides and degradates included in previous
      editions of the PTI from 124 to 492 pesticides and degradates, and includes two
      types of PTI for use in different applications, depending on study objectives.
      The Median-PTI was calculated from median toxicity values for individual
      pesticides, so is robust to outliers and is appropriate for comparing relative
      potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses
      the 5th percentile of available toxicity values, so is a more sensitive screening
      level indicator of potential toxicity. PTI predictions of toxicity in
      environmental samples were tested using data aggregated from published field
      studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia
      in ambient stream water. C. dubia survival was reduced to <=50% of controls in
      44% of samples with Median-PTI values of 0.1-1, and to 0% in 96% of samples with
      Median-PTI values >1. The PTI is a relative, but quantitative, indicator of
      potential toxicity that can be used to evaluate relationships between pesticide
      exposure and biological condition. 

PMID- 24463252
TI  - Analysis of carbon dioxide concentration skewness at a rural site.
AB  - This paper provides evidence that symmetry of CO2 concentration distribution may
      indicate sources or dispersive processes. Skewness was calculated by different
      procedures with CO2 measured at a rural site using a Picarro G1301 analyser over
      a two-year period. The usual skewness coefficient was considered together with
      fourteen robust estimators. A noticeable contrast was obtained between day and
      night, and skewness decreased linearly with the logarithm of the height. One
      coefficient was selected from its satisfactory relationship with the median
      concentration in daily evolution. Three analyses based on the kernel smoothing
      method were conducted with this coefficient to investigate its response to yearly
      and daily evolutions, wind direction, and wind speed. Left-skewed distributions
      were linked to thermal turbulence during midday, especially in spring-summer, or
      with high wind speeds. Almost symmetric distributions were associated with
      sources, such as the Valladolid City plume reinforced with spring emissions and
      the lack of emissions in summer in the remaining directions. Finally, right
      skewed distributions were related to low wind speeds and stable stratification at
      night, furthered by strong emissions in spring. Skewness intervals were proposed
      and their average median concentrations were calculated such that the
      relationship between skewness and concentration depends on the analysis
      performed. Since some skewness coefficients may also be negative, they provide
      better information about sources or dispersive processes than concentration. 

PMID- 24463253
TI  - Flood-related contamination in catchments affected by historical metal mining: an
      unexpected and emerging hazard of climate change.
AB  - Floods in catchments affected by historical metal mining result in the
      remobilisation of large quantities of contaminated sediment from floodplain soils
      and old mine workings. This poses a significant threat to agricultural production
      and is preventing many European river catchments achieving a 'good chemical and
      ecological status', as demanded by the Water Framework Directive. Analysis of
      overbank sediment following widespread flooding in west Wales in June 2012 showed
      that flood sediments were contaminated above guideline pollution thresholds, in
      some samples by a factor of 82. Most significantly, silage produced from flood
      affected fields was found to contain up to 1900 mg kg(-1) of sediment associated
      Pb, which caused cattle poisoning and mortality. As a consequence of climate
      related increases in flooding this problem is likely to continue and intensify.
      Management of contaminated catchments requires a geomorphological approach to
      understand the spatial and temporal cycling of metals through the fluvial system.

PMID- 24463254
TI  - Temporal trends of contaminants in cod from Icelandic waters.
AB  - Contaminants have been analyzed in cod (Gadus morhua) since 1990 as part of the
      national monitoring program for the environmental conditions in the sea around
      Iceland. The aim of this study was to determine the temporal trends of persistent
      organic pollutants (POPs: polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl
      dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), hexachlorocyclohexanes
      (HCHs), chlordanes (CHLs) and toxaphenes (Tox)) and trace elements (As, Cd, Cu,
      Hg, Pb, Se and Zn) in cod over the last two decades at two different locations in
      the Arctic Ocean north of Iceland. The relationship between the contaminant
      concentrations and biological covariates was also determined. All of the POPs
      showed decreasing trends but the trace elements showed no clear signs of trend
      except arsenic which showed an increasing trend and zinc which showed a
      decreasing trend. The concentration of the POPs were lower or similar in the
      Icelandic cod compared to cod sampled in Norway, the Barents Sea and in the
      Baltic Sea, except for HCB which was higher in the Icelandic cod compared to the
      Norwegian cod. The concentration of the trace elements As, Cu, Hg and Zn were
      similar in the Icelandic cod compared to cod sampled in Norway and Greenland but
      the concentration of Cd was higher in the Icelandic cod. The inclusion of the
      biological covariates was found to be important for the statistical analysis. The
      POPs had a positive relationship with liver fat content but negative relationship
      with liver weight. The trace elements had a negative relationship with liver fat
      and liver weight except As which had positive relationship with liver weight.
      Only positive relationships were observed between the contaminant concentrations
      and length. 

PMID- 24463255
TI  - Predictive modeling of groundwater nitrate pollution using Random Forest and
      multisource variables related to intrinsic and specific vulnerability: a case
      study in an agricultural setting (Southern Spain).
AB  - Watershed management decisions need robust methods, which allow an accurate
      predictive modeling of pollutant occurrences. Random Forest (RF) is a powerful
      machine learning data driven method that is rarely used in water resources
      studies, and thus has not been evaluated thoroughly in this field, when compared
      to more conventional pattern recognition techniques key advantages of RF include:
      its non-parametric nature; high predictive accuracy; and capability to determine
      variable importance. This last characteristic can be used to better understand
      the individual role and the combined effect of explanatory variables in both
      protecting and exposing groundwater from and to a pollutant. In this paper, the
      performance of the RF regression for predictive modeling of nitrate pollution is
      explored, based on intrinsic and specific vulnerability assessment of the Vega de
      Granada aquifer. The applicability of this new machine learning technique is
      demonstrated in an agriculture-dominated area where nitrate concentrations in
      groundwater can exceed the trigger value of 50 mg/L, at many locations. A
      comprehensive GIS database of twenty-four parameters related to intrinsic
      hydrogeologic proprieties, driving forces, remotely sensed variables and physical
      chemical variables measured in "situ", were used as inputs to build different
      predictive models of nitrate pollution. RF measures of importance were also used
      to define the most significant predictors of nitrate pollution in groundwater,
      allowing the establishment of the pollution sources (pressures). The potential of
      RF for generating a vulnerability map to nitrate pollution is assessed
      considering multiple criteria related to variations in the algorithm parameters
      and the accuracy of the maps. The performance of the RF is also evaluated in
      comparison to the logistic regression (LR) method using different efficiency
      measures to ensure their generalization ability. Prediction results show the
      ability of RF to build accurate models with strong predictive capabilities.

PMID- 24463256
TI  - Accumulation and effects of the UV-filter octocrylene in adult and embryonic
      zebrafish (Danio rerio).
AB  - Wide application of the UV-filter octocrylene (OC) in cosmetics leads to
      contamination of the aquatic environment, but effects of OC remain unclear. Here
      we determine bioaccumulation and molecular effects of OC. Adult male zebrafish
      were exposed to 22, 209 and 383 MUg/L and embryos to 69, 293 and 925 MUg/L OC. OC
      accumulated in fish up to 17 MUg/g. Calculated BCF varied between 41 and 136.
      Microarray analysis in brain and liver following exposure to 383 MUg/L OC
      revealed alteration of 628 and 136 transcripts, respectively. Most prominent GO
      processes included developmental processes, organ development, hematopoiesis,
      formation of blood vessels, blood circulation, fat cell differentiation and
      metabolism. Validation by RT-qPCR in brain and liver of adult fish and embryos
      included a series of genes. Blood levels of 11-ketotestosterone were not altered.
      The transcriptomics data suggest that OC mainly affects transcription of genes
      related to developmental processes in the brain and liver as well as metabolic
      processes in the liver.

PMID- 24463257
TI  - Ecological risk assessment for small omnivorous mammals exposed to polycyclic
      aromatic hydrocarbons: a case study in northeastern Mexico.
AB  - An ecological risk assessment (ERA) was performed using the hazard quotient (HQ)
      method to evaluate the risks of oral exposure to polycyclic aromatic hydrocarbons
      (PAHs) for medium sized omnivorous mammals. This is the first in a series of
      three papers. In Mexico there is little experience in performing this kind of
      assessment for the terrestrial compartment, in particular for birds and mammals
      exposed to hydrocarbons. The purpose of this paper is to perform an ERA and to
      establish if the omnivorous mammalian species living in the area are at risk of
      adverse effects. The studied site is a land that in past years had been used for
      the disposition of petroleum tank bottom sludges, and scrap metals. Soil and
      water samples were collected and analyzed, and we obtained a list of the site's
      wildlife species as well as samples of the specimens, which were analyzed also.
      HQs were calculated for the hydrocarbons identified as chemicals of potential
      ecological concern (COPECs) and the omnivorous mammals of the site were
      evaluated. Toxicity reference values (TRVs) were taken from the appropriate
      literature, and the doses of exposure were estimated considering the ingestion of
      water, soil, and diet. Results indicated that potential risks associated to the
      oral exposure route were less than benchmarks for effects (in all cases HQ<1).
      The methodology is adequate in terms of the parameters considered in the
      calculations, but it was concluded that in order to reduce uncertainty, more
      research is required in Mexico. This should be primarily aimed at obtaining TRVs
      for mammals, and consider test species with body weights more similar to those
      found in the local fauna. 

PMID- 24463258
TI  - A method for improving reliability and relevance of LCA reviews: the case of life
      cycle greenhouse gas emissions of tap and bottled water.
AB  - The purpose of this study is to propose a method for harmonising Life Cycle
      Assessment (LCA) literature studies on the same product or on different products
      fulfilling the same function for a reliable and meaningful comparison of their
      life-cycle environmental impacts. The method is divided in six main steps which
      aim to rationalize and quicken the efforts needed to carry out the comparison.
      The steps include: 1) a clear definition of the goal and scope of the review; 2)
      critical review of the references; 3) identification of significant parameters
      that have to be harmonised; 4) harmonisation of the parameters; 5) statistical
      analysis to support the comparison; 6) results and discussion. This approach was
      then applied to the comparative analysis of the published LCA studies on tap and
      bottled water production, focussing on Global Warming Potential (GWP) results,
      with the aim to identify the environmental preferable alternative. A statistical
      analysis with Wilcoxon's test confirmed that the difference between harmonised
      GWP values of tap and bottled water was significant. The results obtained from
      the comparison of the harmonised mean GWP results showed that tap water always
      has the best environmental performance, even in case of high energy-consuming
      technologies for drinking water treatments. The strength of the method is that it
      enables both performing a deep analysis of the LCA literature and obtaining more
      consistent comparisons across the published LCAs. For these reasons, it can be a
      valuable tool which provides useful information for both practitioners and
      decision makers. Finally, its application to the case study allowed both to
      supply a description of systems variability and to evaluate the importance of
      several key parameters for tap and bottled water production. The comparative
      review of LCA studies, with the inclusion of a statistical decision test, can
      validate and strengthen the final statements of the comparison. 

PMID- 24463259
TI  - WITHDRAWN: The periodicity of Plasmodium vivax and Plasmodium falciparum in
      Venezuela.

PMID- 24463260
TI  - Effect of mixed infections of Sindbis and La Crosse viruses on replication of
      each virus in vitro.
AB  - Mixed viral infections are ubiquitous in natural populations and may have
      significant but unpredictable biological and epidemiological consequences. These
      infections may be acquired simultaneously (coinfection) or result from two single
      infections at different time intervals (superinfection). This study investigated
      the effect of mixed infections of two mosquito-borne viruses, Sindbis (SINV) and
      La Crosse (LACV), on the replication of each virus in vertebrate baby hamster
      kidney (BHK) and invertebrate Aedes albopictus (C6/36) cell lines. SINV and LACV
      were inoculated onto confluent monolayers of each cell type either singly,
      simultaneously, or with a 2-h delay between single inoculations and titers for
      each virus were quantified by qRT-PCR. The titers for both viruses were
      significantly higher in BHK compared to C6/36 cells. Mixed infections suppressed
      replication of both viruses in BHK cells except for one superinfection treatment
      where inoculation of SINV ahead of LACV did not result in a reduction in SINV
      titer relative to single infection treatment. In C6/36 cells mixed infections had
      no effect on LACV replication, while coinfection enhanced SINV replication. These
      results demonstrate the potential for mixed viral infections to modify arbovirus
      transmission and pathogenesis. 

PMID- 24463261
TI  - A personal voyage through the proteoglycan field.
AB  - The concept of "proteoglycans" as discrete molecules surfaced some 40 years ago,
      out of previously muddled notions of the extracellular matrix. Core proteins were
      gradually recognized as molecular entities, distinct with regard to location,
      substitution with glycosaminoglycan (GAG) chains and biological function. This
      development is surveyed, with brief outline of methodological approaches,
      biosynthesis, and functional aspects. Special emphasis is given to the impact of
      genomics on the field. Some outstanding unresolved issues are emphasized,
      including regulation of GAG biosynthesis and the specificity of GAG-protein
      interactions.

PMID- 24463262
TI  - Enzymatic modification of corn starch with 4-alpha-glucanotransferase results in
      increasing slow digestible and resistant starch.
AB  - In this study, partial 4-alpha-glucanotransferase (4alphaGT) treatment was used
      to modulate the fine structure responsible for the slow digestion and resistant
      property of starch. Normal corn starch modified using 4alphaGT for 4h showed an
      increase of slowly digestible starch from 9.40% to 20.92%, and resistant starch
      from 10.52 to 17.63%, respectively. The 4alphaGT treatment decreased the content
      of amylose from 32.6% to 26.8%. The molecular weight distribution and chain
      length distribution of 4alphaGT-treated starch showed a reduction of molecular
      weight and a great number of short (DP<13) and long (DP>30) chains through
      cleaving and reorganization of starch molecules. Both the short and long chain
      fractions of modified amylopectin were attributed to the low in vitro
      digestibility. The viscosity was inversely related to the digestibility of the
      4alphaGT-treated starch. These results suggested that the 4alphaGT modified
      starch synthesized the novel amylopectin clusters with slow digestible and
      resistant character. 

PMID- 24463263
TI  - Physicochemical, morphological, and rheological characterization of Xanthosoma
      robustum Lego-like starch.
AB  - This work presents the physicochemical and pasting characterization of isolated
      mafafa starch and mafafa flour (Xanthosoma robustum). According to SEM images of
      mafafa starches in the tuber, these starches form Lego-like shaped structures
      with diameters between 8 and 35 MUm conformed by several starch granules of wedge
      shape that range from 2 to 7 MUm. The isolated mafafa starch is characterized by
      its low contents of protein, fat, and ash. The starch content in isolated starch
      was found to be 88.58% while the amylose content obtained was 35.43%. X-ray
      diffraction studies confirm that isolated starch is composed mainly by
      amylopectin. These results were confirmed by differential scanning calorimetry
      and thermo gravimetric analysis. This is the first report of the molecular
      parameters for mafafa starch: molar mass that ranged between 2*10(8) and 4*10(8)
      g/mol, size (Rg) value between 279 and 295 nm, and molecular density value
      between 9.2 and 9.7 g/(mol nm(3)). This study indicates that mafafa starch shows
      long chains of amylopectin this fact contributes to higher viscosity development
      and higher gel stability. The obtained gel phase is transparent in the UV-vis
      region. The viscosity, gel stability and optical properties suggest that there is
      potential for mafafa starch applications in the food industry.

PMID- 24463264
TI  - Effects of partial desulfation on antioxidant and inhibition of DLD cancer cell
      of Ulva fasciata polysaccharide.
AB  - Ulva fasciata belonging to the family Ulvaceae, commonly known as 'sea lettuce',
      is an abundantly growing green seaweed in coastal seashore of South China. Three
      different molecular weight sulfated polysaccharides (UFP1, UFP2 and UFP3) were
      extracted and separated from U. fasciata by hot water extraction and
      ultrafiltration. The three native UFP fractions had partial desulfurization by
      solvolytic desulfation respectively and the effect of sulfate content on the
      exhibition of the antioxidant and anti-tumor capacities had been evaluated and
      compared. The results showed that each native polysaccharide (UFP1, UFP2, UFP3)
      with high sulfate content exhibited better antioxidant activities compared with
      the partial desulfated polysaccharides (DS-UFP1, DS-UFP2, DS-UFP3). Specifically,
      UFP2 with relatively high sulfate content, molecular weight and uronic acid
      content had consistently excellent antioxidant performances. However, UFP2
      demonstrated the minimal inhibitory effects on growth of DLD intestinal cancer
      cells. Instead, DS-UFP3 with the lowest sulfate content but highest uronic acid
      content and molecular weight exhibited the best antitumor activity. 

PMID- 24463265
TI  - In vitro aceclofenac release from IPN matrix tablets composed of chitosan
      tamarind seed polysaccharide.
AB  - This communication describes the formulation and in vitro evaluation of IPN
      matrix tablets of aceclofenac. IPN microparticles using chitosan and tamarind
      seed polysaccharide blend was prepared using glutaraldehyde as cross-linker. The
      drug entrapment efficiency and average particle size of these microparticles was
      found to be 91.97+/-1.30% and 498.12+/-38.67 MUm, respectively. These IPN
      microparticles were characterized by scanning electron microscopy (SEM) and
      powder X-ray diffraction (P-XRD) study. These microparticles were compressed with
      tablet excipients through direct compression technique. These matrix tablets
      showed sustained aceclofenac release over 8 h. These matrix tablets might be
      helpful to minimize dosing frequency and reduction of various side effects during
      prolong period of treatment.

PMID- 24463266
TI  - Nanoreticulations of etherified locust bean polysaccharide for controlled oral
      delivery of lamivudine.
AB  - Herein, an aqueous solution of etherified locust bean polysaccharide (ELBP)
      containing lamivudine was reticulated in presence of trivalent aluminium (Al(3+))
      ions to nanoscale level (43.82-197.70 nm) by surfactant assisted homogenization
      reticulation technique. The variation in aluminium chloride (AlCl3) strength (1.5
      3.5% (w/v)) and drug:ELBP weight ratio (0.11-0.43) affected the properties of the
      nanoreticulations. Regardless of the variables, a maximum of ~44% drug entrapment
      efficiency was noted. In simulated intestinal fluid (phosphate buffer solution,
      pH 7.4), the drug release rate was inversely proportional to the strength of
      AlCl3; but followed a proportional relationship with the drug:ELBP ratio. The
      mechanism of drug release shifted from Fickian diffusion to anomalous transport
      as the salt strength was increased above 2.5% (w/v). At intermediate drug:ELBP
      ratio, the drug release rate was regulated by polymer chain relaxation as opposed
      to simple diffusion mechanism. Fourier transform infrared spectroscopy did not
      show any evidence of chemical interaction between the drug and ELBP. Thermal
      analysis and X-ray diffraction studies suggested amorphous dispersion of drug in
      the nanoreticulations. Thus, the nanoreticulations were expected to absorb via
      intestine and phagocytosed by the virus-infected hepatic macrophages and hence
      could be useful for controlled delivery of lamivudine avoiding dose-dependent
      toxicity of the drug.

PMID- 24463267
TI  - The design of propolis flavone microemulsion and its effect on enhancing the
      immunity and antioxidant activity in mice.
AB  - The objective of the present study was to formulate a microemulsion system for
      improving the activity of propolis flavone (PF). Pseudo-ternary phase diagrams
      were constructed to evaluate the existence area of PF microemulsion (PFM). The
      formulation was characterized by particle size, zeta potential, morphology and
      stability. The results showed that the optimal PFM formulation consists of 5.3%
      ethyl acetate, 14% RH-40, 7% ethanol and 73.7% water (w/w), with a solubility of
      PF up to 3.0 mg mL(-1). The immune-enhancing and antioxidant activity of PFM in
      vitro and in vivo were performed. The results showed that PFM could significantly
      promote the splenocyte proliferation and the secretion of IL-2 and IFN-gamma in
      vitro. In vivo, PFM at high and medium doses was able to significantly increase
      the thymus and spleen indices, enhance splenocyte activity and improve the
      contents of IgG and IgM in serum, it could also improve the antioxidant activity,
      significantly increase the levels of superoxidase dismutase and glutathione
      peroxidase, and decrease the malondialdehyde levels compared with PF. These
      results indicated that microemulsion could be used as an effective formulation
      for enhancing the activity of PF. Therefore, microemulsion would be expected to
      exploit into a new-type preparation of PF.

PMID- 24463268
TI  - Characterization of core-shell calcium-alginate macrocapsules fabricated by
      electro-coextrusion.
AB  - Spherical macrocapsules, where calcium-alginate shell enclosed olive oil as a
      model core medium, were fabricated by electro-coextrusion. The effects of three
      key process factors, including alginate concentration in shell fluid (0.5-4.0%),
      shell-to-core flow rate ratio (4-12 at a fixed core flow rate of 0.05 mL/min),
      and applied voltage (0-10 kV), on the morphological and textural characteristics
      of the macrocapsules were analyzed using response surface methodology. The
      analysis showed that the diameter, shell thickness, hardness, and breaking energy
      of the macrocapsules were in the ranges of 0.89-1.61 mm, 17.4-66.4 MUm, 1.37
      11.01 N, and 0.34-6.90 mJ, respectively, and strongly influenced by all the three
      factors, except that the surface appearance was only significantly affected by
      the shell-to-core flow rate ratio. The process factors were also optimized for
      the practically useful macrocapsules, having non-oily surface and hardness larger
      than 3 N, using a graphical optimization technique.

PMID- 24463269
TI  - Immunomodulatory properties of the vaccine adjuvant alum.
AB  - Alum, the most common adjuvant in non-living vaccines, has a record of successful
      use in human vaccination where it promotes antibody-mediated protective immunity.
      However, alum is a poor inducer of cellular immune responses. The mechanism
      underlying the selective enhancement of humoral immunity is still not well
      understood. Here, to provide an insight into its mode of action, recent findings
      regarding innate immune responses induced by alum and their impact on adaptive
      immunity are described, with a particular emphasis on early recognition of alum,
      including NLRP3 and PI3 kinase activation, adjuvant-induced cell death and the
      release of endogenous danger signals. Expanding our knowledge of alum-induced
      immunomodulation will greatly enhance our capacity to rationally develop novel
      adjuvants with specific properties. 

PMID- 24463271
TI  - Oral ingestion of Microbacterium nematophilum leads to anal-region infection in
      Caenorhabditis elegans.
AB  - Microbacterium nematophilum is a gram positive bacterium that colonizes the
      Caenorhabditis elegans rectal region causing swelling and constipation. This
      interaction has been exploited as a model system to identify and study genes
      important in host-pathogen interactions and innate immunity. During attempts to
      inhibit the host-pathogen interaction, it became important to clarify the route
      of infection. Using bacteria labeled with the fluorescent dye Cy3, we show that
      infection is via the oral route only and that infection follows a clear pattern
      of ingestion, plug formation, and bump development that can be quantitatively
      tracked over time. 

PMID- 24463270
TI  - Targeted extracellular signal-regulated kinase activation mediated by Leishmania
      amazonensis requires MP1 scaffold.
AB  - Leishmania amazonensis infection promotes alteration of host cellular signaling
      and intracellular parasite survival, but specific mechanisms are poorly
      understood. We previously demonstrated that L. amazonensis infection of dendritic
      cells (DC) activated extracellular signal-regulated kinase (ERK), an MAP-kinase
      kinase kinase, leading to altered DC maturation and non-healing cutaneous
      leishmaniasis. Studies using growth factors and cell lines have shown that
      targeted, robust, intracellular phosphorylation of ERK1/2 from phagolysosomes
      required recruitment and association with scaffolding proteins, including p14/MP1
      and MORG1, on the surface of late endosomes. Based on the intracellular
      localization of L. amazonensis within a parasitophorous vacuole with late
      endosome characteristics, we speculated that scaffolding proteins would be
      important for intracellular parasite-mediated ERK signaling. Our findings
      demonstrate that MP1, MORG1, and ERK all co-localized on the surface of parasite
      containing LAMP2-positive phagolysosomes. Infection of MEK1 mutant fibroblasts
      unable to bind MP1 demonstrated dramatically reduced ERK1/2 phosphorylation
      following L. amazonensis infection but not following positive control EGF
      treatment. This novel mechanism for localization of intracellular L. amazonensis
      mediated ERK1/2 phosphorylation required the endosomal scaffold protein MP1 and
      localized to L. amazonensis parasitophorous vacuoles. Understanding how L.
      amazonensis parasites hijack host cell scaffold proteins to modulate signaling
      cascades provides targets for antiprotozoal drug development. 

PMID- 24463273
TI  - [Human dignity and human rights].

PMID- 24463272
TI  - Histone variants: the tricksters of the chromatin world.
AB  - The eukaryotic genome exists in vivo at an equimolar ratio with histones, thus
      forming a polymer composed of DNA and histone proteins. Each nucleosomal unit in
      this polymer provides versatile capabilities and dynamic range. Substitutions of
      the individual components of the histone core with structurally distinct histone
      variants and covalent modifications alter the local fabric of the chromatin
      fiber, resulting in epigenetic changes that can be regulated by the cell. In this
      review, we highlight recent advances in the study of histone variant structure,
      assembly, and inheritance, their influence on nucleosome positioning, and their
      cumulative effect upon gene expression, DNA repair and the progression of
      disease. We also highlight fundamental questions that remain unanswered regarding
      the behavior of histone variants and their influence on cellular function in the
      normal and diseased states. 

PMID- 24463274
TI  - Complete genome sequence of Bacillus amyloliquefaciens LFB112 isolated from
      Chinese herbs, a strain of a broad inhibitory spectrum against domestic animal
      pathogens.
AB  - Bacillus amyloliquefaciens LFB112, isolated from Chinese herbs, displays a broad
      inhibitory activity against an array of pathogens involved in domestic animal
      diseases. Here, we present the complete genome sequence of B. amyloliquefaciens
      LFB112, providing insights into the genomic basis of its effects and facilitating
      its application in animal production. 

PMID- 24463275
TI  - Cytokine profiles in polycythemia vera and essential thrombocythemia patients:
      clinical implications.
AB  - Studies have shown that the clinical impact of Janus kinase 2 (JAK2) inhibitors
      in primary myelofibrosis patients is due to the regulation of cytokine levels,
      suggesting that cytokine profiles might play a critical role in
      myeloproliferative neoplasms (MPNs) physiopathology. In this study, we compared
      the plasma cytokine profiles of polycythemia vera (PV) patients and essential
      thrombocythemia (ET) patients as a function of their JAK2 V617F status and the
      presence of thrombohemorrhagic complications. Using a multiplex cytokine assay,
      cytokine measurements were taken of the plasma of 17 PV patients and 21 ET
      patients. Twenty-two of these patients (10 PV and 12 ET) experienced at least one
      thrombohemorrhagic manifestation before diagnosis. We showed that cytokine levels
      were significantly increased in PV and ET patients compared with normal values
      and that several positive correlations existed between the cytokine
      concentrations and the biological parameters in each MPN. The comparison between
      the cytokine profiles of ET and PV patients showed a statistically significant
      increase of interleukin (IL)-4, IL-8, granulocyte macrophage-colony stimulating
      factor, interferon -gamma, monocyte chemotactic protein -1, platelet derived
      growth factor-BB, and vascular endothelial growth factor in the ET group. Only
      tumor necrosis factor-alpha and platelet derived growth factor-BB were
      specifically impacted by the JAK2 V617F status of the PV and ET patients,
      respectively, suggesting that there are both JAK2 V617F-driven and JAK2 V617F
      independent inflammatory responses in MPNs. We also showed that the subgroup of
      PV patients with vascular complications displayed significantly different
      concentrations of IL-12(p70) and granulocyte macrophage-colony stimulating factor
      compared with patients without vascular complications. Altogether, these data
      suggest that cytokine measurement might be useful for the clinical and
      therapeutic stratification of PV and ET patients. 

PMID- 24463276
TI  - Stage-specific functional roles of integrins in murine erythropoiesis.
AB  - When the erythroid integrins alpha5beta1 and alpha4beta1 were each deleted
      previously at the stem cell level, they yielded distinct physiologic responses to
      stress by affecting erythoid expansion and terminal differentiation or only the
      latter, respectively. To test at what stage of differentiation the integrin
      effects were exerted, we created mice with alpha4- or alpha5-integrin deletions
      only in erythroid cells and characterized them at homeostasis and after
      phenylhydrazine-induced hemolytic stress. Unlike our prior data, the phenotype of
      mice with alpha5-erythroid deletions was similar to controls, especially after
      stress. These outcomes seem to reconcile divergent prior views on the role of
      alpha5-integrin in erythropoiesis. By contrast, alpha4 integrins whether deleted
      early or late have a dominant effect on bone marrow retention of erythroblasts
      and on terminal erythroid maturation at homeostasis and after stress. 

PMID- 24463277
TI  - Translation of branched-chain aminotransferase-1 transcripts is impaired in cells
      haploinsufficient for ribosomal protein genes.
AB  - Diamond-Blackfan anemia (DBA) is a bone marrow failure syndrome linked to
      mutations in ribosomal protein (RP) genes that result in the impaired
      proliferation of hematopoietic progenitor cells. The etiology of DBA is not
      completely understood; however, the ribosomal nature of the genes involved has
      led to speculation that these mutations may alter the landscape of messenger RNA
      (mRNA) translation. Here, we performed comparative microarray analysis of
      polysomal mRNA transcripts isolated from lymphoblastoid cell lines derived from
      DBA patients carrying various haploinsufficient mutations in either RPS19 or
      RPL11. Different spectrums of changes were observed depending on the mutant gene,
      with large differences found in RPS19 cells and very few in RPL11 cells. However,
      we find that the small number of altered transcripts in RPL11 overlap for the
      most part with those altered in RPS19 cells. We show specifically that levels of
      branched-chain aminotransferase-1 (BCAT1) transcripts are significantly decreased
      on the polysomes of both RPS19 and RPL11 cells and that translation of BCAT1
      protein is especially impaired in cells with small RP gene mutations, and we
      provide evidence that this effect may be due in part to the unusually long 5'UTR
      of the BCAT1 transcript. The BCAT1 enzyme carries out the final step in the
      biosynthesis and the first step of degradation of the branched-chain amino acids
      leucine, isoleucine, and valine. Interestingly, several animal models of DBA have
      reported that leucine ameliorates the anemia phenotypes generated by RPS19 loss.
      Our study suggests that RP mutations affect the synthesis of specific proteins
      involved in regulating amino acid levels that are important for maintaining the
      normal proliferative capacity of hematopoietic cells.

PMID- 24463278
TI  - Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: mechanism,
      function, and implication for a potential novel therapeutic target.
AB  - Treatment for high-risk pediatric and adult acute B cell lymphoblastic leukemia
      (B-ALL) remains challenging. Exploring novel pathways in B-ALL could lead to new
      therapy. Our previous study has shown that stem cell factor SALL4 is aberrantly
      expressed in B-ALL, but its functional roles and the mechanism that accounts for
      its upregulation in B-ALL remain unexplored. To address this question, we first
      surveyed the existing B-ALL cell lines and primary patient samples for SALL4
      expression. We then selected the B-ALL cell lines with the highest SALL4
      expression for functional studies. RNA interference was used to downregulate
      SALL4 expression in these cell lines. When compared with control cells, SALL4
      knockdown cells exhibited decreased cell proliferation, increased apoptosis in
      vitro, and decreased engraftment in a xenotransplant model in vivo. Gene
      expression analysis showed that in SALL4 knockdown B-ALL cells, multiple caspase
      members involved in cell apoptosis pathway were upregulated. Next, we explored
      the mechanisms of aberrant SALL4 expression in B-ALL. We found that
      hypomethylation of the SALL4 CpG islands was correlated with its high expression.
      Furthermore, treatment of low SALL4-expressing B-ALL cell lines with DNA
      methylation inhibitor led to demethylation of the SALL4 CpG and increased SALL4
      expression. In summary, to our knowledge, we are the first to show that the
      aberrant expression of SALL4 in B-ALL is associated with hypomethylation, and
      that SALL4 plays a key role in B-ALL cell survival and could be a potential novel
      target in B-ALL treatment.

PMID- 24463279
TI  - Editorial commentary: imminent challenges: carbapenem-resistant
      enterobacteriaceae in transplant recipients and patients with hematologic
      malignancy.

PMID- 24463280
TI  - The global challenge of carbapenem-resistant Enterobacteriaceae in transplant
      recipients and patients with hematologic malignancies.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are emerging global pathogens. The
      spread of CRE to transplant recipients and patients with hematologic malignancies
      has ominous implications. These patients rely on timely, active antibacterial
      therapy to combat gram-negative infections; however, recommended empirical
      regimens are not active against CRE. Approximately 3%-10% of solid organ
      transplant (SOT) recipients in CRE-endemic areas develop CRE infection, and the
      infection site correlates with the transplanted organ. Mortality rates associated
      with CRE infections approach 40% in SOT recipients and 65% in patients with
      hematologic malignancies. Given that the current antimicrobial armamentarium to
      combat CRE is extremely limited, a multifaceted approach that includes
      antimicrobial stewardship and active surveillance is needed to prevent CRE
      infections in immunocompromised hosts. Improving outcomes of established
      infections will require the use of risk factor-based prediction tools and
      molecular assays to more rapidly administer CRE-active therapy and the
      development of new antimicrobial agents with activity against CRE.

PMID- 24463282
TI  - [Chemoprevention of colorectal cancer in inflammatory bowel disease].
AB  - The risk of developing colorectal cancer is increased in patients with
      inflammatory bowel disease. Surveillance colonoscopy has not been shown to
      prolong survival and rates of interval cancer are reported to be high. Continuing
      colonic inflammation has been shown to be important in the development of
      colorectal cancer and therefore anti-inflammatory agents such as the 5
      aminosalicylates and immunomodulators have been considered as potential
      chemopreventive agents. This review focuses on various chemopreventive agents
      that have been clearly shown to reduce the risk of colorectal adenoma and cancer
      in the patients with inflammatory bowel disease.

PMID- 24463283
TI  - [Usefulness of polyp and adenoma detection rate in the proximal and distal
      colon].
AB  - BACKGROUND/AIMS: The polyp detection rate (PDR) has been suggested as a surrogate
      for adenoma detection rate (ADR). The purpose of this study was to determine the
      level of agreement between PDR and ADR in the proximal and distal colon. METHODS:
      A total of 1,937 consecutive, asymptomatic individuals aged 40 years and older
      who underwent colonoscopies at six academic teaching hospitals in Korea were
      included in this study. PDR and ADR were calculated for each colonic segment. PDR
      was compared with ADR in the proximal and distal colon. RESULTS: During 1,937
      colonoscopies, 1,862 polyps were removed; 1,421 (76%) were adenomas. The PDR and
      ADR in the proximal colon was 25.8% and 22.8%, respectively (kappa value=0.917,
      p=0.26), and that in the distal colon was 28.9% and 22.2%, respectively
      (p<0.001). There was a strong correlation between PDR and ADR in the proximal
      colon, but diverged in sigmoid colon and rectum. CONCLUSIONS: PDR and ADR
      correlate well in the proximal colon, but not in the distal colon, especially
      sigmoid and rectum. PDR should be measured for each colonic segment when using
      PDR as a surrogate for ADR. PDR is a valid proxy for ADR in the proximal colon.

PMID- 24463284
TI  - FOLFIRI as second-line chemotherapy after failure of FOLFOX4 in advanced
      colorectal cancer: a Korean single-center experience.
AB  - BACKGROUND/AIMS: The incidence of colorectal cancer has been increasing every
      year in Korea. Irinotecan- or oxaliplatin-based regimens including biologic
      agents are known to be effective in patients with advanced colorectal cancer. But
      in practice, FOLFOX (combination of oxaliplatin, 5-fluorouracil, and leucovorin)
      or FOLFIRI (combination of irinotecan, 5-fluorouracil, and leucovorin) regimens
      without biologic agents are more commonly used in Korea due to of the high costs
      of biologic agents. The aim of this study was to evaluate the efficacy and
      toxicity of FOLFIRI following FOLFOX4 in patients with advanced colorectal
      cancer. METHODS: A total of 54 patients with advanced colorectal cancer who were
      treated between May 2005 and May 2013 with FOLFOX4 as first-line chemotherapy and
      with FOLFIRI as second-line chemotherapy at Kosin University Gospel Hospital
      (Busan, Korea) were reviewed retrospectively. RESULTS: A total of 54 patients
      received second-line FOLFIRI chemotherapy. Five patients (9.3%) had a partial
      response, 29 patients (53.7%) had a stable disease. The median overall survival
      was 8.90 months and the median time to progression was 4.33 months. Toxicities
      were tolerable. CONCLUSIONS: In a Korean population, FOLFIRI as second-line
      chemotherapy is effective and well tolerated in patients with advanced colorectal
      cancer after failure of FOLFOX4. Although the efficacy of FOLFIRI in this study
      was lower than that of second-line FOLFIRI with biologic agents, these results
      can help in the formulation of a treatment strategy for financially troubled
      patients.

PMID- 24463285
TI  - Clinical features and risk factors for severe complications among patients with
      acute hepatitis A virus infection in the Jeonbuk Province of Korea.
AB  - BACKGROUND/AIMS: The frequency of symptomatic acute HAV infections in adulthood
      are increasing in Korea. This study analyzes the clinical severity in patients
      with acute HAV infection and investigates risk factors associated with three
      severe complications: prolonged cholestasis, acute kidney injury, and acute liver
      failure. METHODS: We performed a retrospective analysis of 726 patients diagnosed
      from January 2006 to December 2010 at three tertiary hospitals in Jeonbuk
      Province, Republic of Korea with acute HAV infection. RESULTS: In the group of
      726 patients, the mean age was 30.3 years, 426 (58.6%) were male, and 34 (4.7%)
      were HBsAg positive. Severe complications from acute HAV infection occurred as
      follows: prolonged cholestasis in 33 (4.6%), acute kidney injury in 17 (2.3%),
      and acute liver failure in 16 (2.2%). Through multivariate analysis, age >=40
      years (OR 2.63, p=0.024) and peak PT (INR) >=1.5 (OR 5.81, p=0.035) were found to
      be significant risk factors for prolonged cholestasis. Age >=40 years (OR 5.24,
      p=0.002) and female gender (OR 3.11, p=0.036) were significant risk factors for
      acute kidney injury. Age >=40 years (OR 6.91, p=0.002), HBsAg positivity (OR
      5.02, p=0.049), and peak total bilirubin (OR 1.11, p=0.001) were significant risk
      factors for acute liver failure. CONCLUSIONS: Age >=40 years, female gender,
      HBsAg positivity, peak PT (INR) >=1.5, and peak total bilirubin were significant
      risk factors for severe complications in acute HAV infections.

PMID- 24463286
TI  - Percutaneous cholecystostomy is appropriate as definitive treatment for acute
      cholecystitis in critically ill patients: a single center, cross-sectional study.
AB  - BACKGROUND/AIMS: Percutaneous cholecystostomy (PC) is an effective treatment for
      cholecystitis in high-risk surgical patients. However, there is no definitive
      agreement on the need for additional cholecystectomy in these patients. METHODS:
      All patients who were admitted to Cheju Halla General Hospital (Jeju, Korea) for
      acute cholecystitis and who underwent ultrasonography-guided PC between 2007 and
      2012 were consecutively enrolled in this study. Among 82 total patients enrolled,
      35 underwent laparoscopic cholecystectomy after recovery and 47 received the best
      supportive care (BSC) without additional surgery. RESULTS: The technical and
      clinical success rates for PC were 100% and 97.5%, respectively. The overall mean
      survival was 12.8 months. In the BSC group, mean survival was 5.4 months, and in
      the cholecystectomy group, mean survival was 22.4 months (p<0.01). However, there
      was no significant difference between these groups in multivariate analysis
      (relative risk [RR]=1.92; 95% CI, 0.77-4.77; p=0.16). However, advanced age
      (RR=1.05; 95% CI, 1.02-1.08; p=0.001) and higher class in the American Society of
      Anesthesiologists' physical status (RR=3.06; 95% CI, 1.37-6.83, p=0.006) were
      significantly associated with survival in the multivariate analysis. Among the 47
      patients in the BSC group, the cholecystostomy tube was removed in 31 patients
      per protocol. Recurrent cholecystitis was not observed in either group of
      patients during the follow-up period. CONCLUSIONS: In high-risk surgical
      patients, PC without additional cholecystectomy might be the best definitive
      management. Furthermore, the cholecystostomy drainage catheter can be safely
      removed in certain patients.

PMID- 24463281
TI  - Disparities in the quality of HIV care when using US Department of Health and
      Human Services indicators.
AB  - We estimated US Department of Health and Human Services (DHHS)-approved human
      immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in
      care, 82% were prescribed treatment, and 78% had HIV RNA <=200 copies/mL; younger
      adults, women, blacks, and injection drug users had poorer outcomes.
      Interventions are needed to reduce retention- and treatment-related disparities.

PMID- 24463287
TI  - [Early gastric cancer with cellulitis-like skin metastasis].
AB  - Skin metastasis from internal carcinoma rarely occurs and it has an incidence of
      0.7% to 9%. Although the prognosis of the skin metastases varies considerably
      depending on the type of the primary malignancy, presence of metastatic skin
      cancer usually implies a widespread systemic disease and a high mortality. A 50
      year-old Korean male patient visited Dankook University Hospital for evaluation
      of skin rash on his whole abdomen of about 1 month's duration. He had undergone
      laparoscopy-assisted distal gastrectomy due to early gastric cancer about 3
      months ago. He did not complain of any noticeable symptoms like febrile sense or
      pruritus. Skin biopsy was performed on the periumbilical area at previous port
      site and around the scar. Microscopic examination revealed multiple malignant
      cells in lymphatic spaces, consistent with metastatic carcinoma. He was therefore
      diagnosed with isolated skin metastasis from early gastric cancer. Because of
      patient's poor liver function, systemic chemotherapy could not be performed and
      only best supportive care was provided. Herein, we report a rare case of
      cellulitis-like skin metastasis from early gastric cancer with a brief review of
      the literature.

PMID- 24463288
TI  - An arteriovenous malformation in the jejunum mimicking a gastrointestinal stromal
      tumor.
AB  - A 51-year-old man visited the tertiary-care hospital with a 2-week history of
      dizziness and dyspnea on exertion. The initial hemoglobin level was 5.8 g/dL,
      without any history of hematochezia or melena. The esophagogastroduodenoscopy
      (EGD) was normal. During colonoscopic preparation, the patient experienced
      hematochezia and became hypotensive. On angiography, no extravasation of contrast
      media was observed. A CT scan with angiography showed a small high-density area
      in the jejunal lumen, suggesting extravasation of the contrast media. Capsule
      endoscopy was performed, and oozing bleeding was suspected in the proximal to mid
      jejunum. The patient was referred to our hospital. Repeated EGD and CT
      enterography did not reveal any significant bleeding. An antegrade double balloon
      endoscopy was performed, and an approximately 2-cm-sized submucosal tumor with
      ulceration and a non-bleeding exposed vessel was observed in the mid jejunum. The
      presumed diagnosis was jejunal gastrointestinal stromal tumor. The mass was
      surgically resected, and the final histopathological diagnosis was arterio-venous
      malformation.

PMID- 24463289
TI  - Liver abscess in advanced hepatocellular carcinoma after sorafenib treatment.
AB  - Hepatocellular carcinoma (HCC) is a critical global health issue and the third
      most common cause of cancer-related deaths worldwide. The majority of patients
      who present HCC are already at an advanced stage and their tumors are
      unresectable. Sorafenib is a multi-kinase inhibitor of the vascular endothelial
      growth factor pathway and was recently introduced as a therapy for advanced HCC.
      Furthermore, studies have shown that oral sorafenib has beneficial effects on
      survival. However, many patients experience diverse side effects, and some of
      these are severe. Liver abscess development has not been previously documented to
      be associated with sorafenib administration in HCC. Here, we report the case of a
      HCC patient that developed a liver abscess while being treated with sorafenib.

PMID- 24463290
TI  - [A case of gallbladder tuberculosis diagnosed by positive tuberculosis-polymerase
      chain reaction].
AB  - Gallbladder tuberculosis is an extremely rare disease that is rarely reported in
      the literature. Arriving at the correct diagnosis of gallbladder tuberculosis is
      difficult, and it is usually made by histopathologic examination after
      cholecystectomy. However, due to the low sensitivity of acid-fast stain and
      culture result, diagnosing gallbladder tuberculosis is still demanding even after
      tissue acquisition. To overcome this problem, tuberculosis-polymerase chain
      reaction (TB-PCR) is performed on the resected specimen, which has high
      sensitivity and specificity. A 70-year-old female who had previously undergone
      total gastrectomy for advanced gastric cancer was admitted with right upper
      quadrant pain. Abdominal ultrasonography and computed tomography revealed acute
      cholecystitis without gallstones or sludge. She underwent cholecystectomy and the
      histopathologic finding of the specimen showed chronic active cholecystitis
      without gallstones or sludge. Because she was suspected to have pulmonary
      tuberculosis, TB-PCR was also performed on the resected gallbladder. TB-PCR
      showed positive reaction for Mycobacterium tuberculosis and we could diagnose it
      as gallbladder tuberculosis. Herein, we present a case of gallbladder
      tuberculosis diagnosed by TB-PCR from resected gallbladder.

PMID- 24463291
TI  - Chronic exposure to Rhodobacter sphaeroides extract LycogenTM prevents UVA
      induced malondialdehyde accumulation and procollagen I down-regulation in human
      dermal fibroblasts.
AB  - UVA contributes to the pathogenesis of skin aging by downregulation of
      procollagen I content and induction of matrix metalloproteinase (MMP)-associated
      responses. Application of antioxidants such as lycopene has been demonstrated as
      a convenient way to achieve protection against skin aging. LycogenTM, derived
      from the extracts of Rhodobacter sphaeroides, exerts several biological effects
      similar to that of lycopene whereas most of its anti-aging efficacy remains
      uncertain. In this study, we attempted to examine whether LycogenTM could
      suppress malondialdehyde (MDA) accumulation and restore downregulated procollagen
      I expression induced by UVA exposure. In human dermal fibroblasts Hs68 cells, UVA
      repressed cell viability and decreased procollagen I protein content accompanied
      with the induction of MMP-1 and MDA accumulation. Remarkably, incubation with 50
      uM LycogenTM for 24 h ameliorated UVA-induced cell death and restored UVA-induced
      downregulation of procollagen in a dose-related manner. LycogenTM treatment also
      prevented the UVA-induced MMP-1 upregulation and intracellular MDA generation in
      Hs68 cells. Activation of NFkappaB levels, one of the downstream events induced
      by UVA irradiation and MMP-1 induction, were also prevented by LycogenTM
      administration. Taken together, our findings demonstrate that LycogenTM may be an
      alternative agent that prevents UVA-induced skin aging and could be used in
      cosmetic and pharmaceutical applications. 

PMID- 24463292
TI  - Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3
      transgenic mice.
AB  - T helper (Th)2 cells have been proposed to play a neuroprotective role in
      multiple sclerosis (MS). This is mainly based on "loss-of-function" studies in an
      animal model for MS, experimental autoimmune encephalomyelitis (EAE), using
      blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2
      related molecules. We tested whether an increase of Th2 responses ("gain-of
      function" approach) could alter EAE, the approach of novel GATA binding protein 3
      (GATA3)-transgenic (tg) mice that overexpress GATA3, a transcription factor
      required for Th2 differentiation. In EAE induced with myelin oligodendrocyte
      glycoprotein (MOG)35-55 peptide, GATA3-tg mice had a significantly delayed onset
      of disease and a less severe maximum clinical score, compared with wild-type
      C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis
      and demyelination in the spinal cord, and anti-inflammatory cytokine profiles
      immunologically, however both groups developed similar levels of MOG-specific
      lymphoproliferative responses. During the early stage, we detected higher levels
      of interleukin (IL)-4 and IL-10, with MOG and mitogen stimulation of regional
      lymph node cells in GATA3-tg mice. During the late stage, only mitogen
      stimulation induced higher IL-4 and lower interferon-gamma and IL-17 production
      in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2
      immune response may reduce the severity of inflammatory demyelinating diseases,
      including MS. 

PMID- 24463294
TI  - Expanding antibiotics studies to include bioactive substance science.

PMID- 24463296
TI  - Christopher Walsh: Pioneer and innovator in antibiotic and natural product
      chemical biology.

PMID- 24463297
TI  - Establishment of a rescue system for an autonomous Parvovirus mink enteritis
      virus.
AB  - Construction and characterization of a full-length infectious clone (pMEV) of
      mink enteritis virus are described. Feline kidney cells (F81) were transfected
      with pMEV containing an engineered BamHI site that served as a genetic marker.
      The rescued virus was indistinguishable from its parental virus. The availability
      of a MEV infectious clone will facilitate studies of viral replication and
      pathogenicity and will permit the elucidation of determinants of the host range
      of the parvovirus. 

PMID- 24463298
TI  - Targeting cancer stem cells by curcumin and clinical applications.
AB  - Curcumin is a well-known dietary polyphenol derived from the rhizomes of
      turmeric, an Indian spice. The anticancer effect of curcumin has been
      demonstrated in many cell and animal studies, and recent research has shown that
      curcumin can target cancer stem cells (CSCs). CSCs are proposed to be responsible
      for initiating and maintaining cancer, and contribute to recurrence and drug
      resistance. A number of studies have suggested that curcumin has the potential to
      target CSCs through regulation of CSC self-renewal pathways (Wnt/beta-catenin,
      Notch, sonic hedgehog) and specific microRNAs involved in acquisition of
      epithelial-mesenchymal transition (EMT). The potential impact of curcumin, alone
      or in combination with other anticancer agents, on CSCs was evaluated as well.
      Furthermore, the safety and tolerability of curcumin have been well-established
      by numerous clinical studies. Importantly, the low bioavailability of curcumin
      has been dramatically improved through the use of structural analogues or special
      formulations. More clinical trials are underway to investigate the efficacy of
      this promising agent in cancer chemoprevention and therapy. In this article, we
      review the effects of curcumin on CSC self-renewal pathways and specific
      microRNAs, as well as its safety and efficacy in recent human studies. In
      conclusion, curcumin could be a very promising adjunct to traditional cancer
      treatments. 

PMID- 24463293
TI  - Use of genetically modified mesenchymal stem cells to treat neurodegenerative
      diseases.
AB  - The transplantation of mesenchymal stem cells (MSCs) for treating
      neurodegenerative disorders has received growing attention recently because these
      cells are readily available, easily expanded in culture, and when transplanted,
      survive for relatively long periods of time. Given that such transplants have
      been shown to be safe in a variety of applications, in addition to recent
      findings that MSCs have useful immunomodulatory and chemotactic properties, the
      use of these cells as vehicles for delivering or producing beneficial proteins
      for therapeutic purposes has been the focus of several labs. In our lab, the use
      of genetic modified MSCs to release neurotrophic factors for the treatment of
      neurodegenerative diseases is of particular interest. Specifically, glial cell
      derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain derived
      neurotrophic factor (BDNF) have been recognized as therapeutic trophic factors
      for Parkinson's, Alzheimer's and Huntington's diseases, respectively. The aim of
      this literature review is to provide insights into: (1) the inherent properties
      of MSCs as a platform for neurotrophic factor delivery; (2) the molecular tools
      available for genetic manipulation of MSCs; (3) the rationale for utilizing
      various neurotrophic factors for particular neurodegenerative diseases; and (4)
      the clinical challenges of utilizing genetically modified MSCs. 

PMID- 24463299
TI  - The priority group index: a proposed new method incorporating high risk and
      population burden to identify target populations for public health interventions.
AB  - CONTEXT: Selection of priority groups is important for health interventions.
      However, no quantitative method has been developed. OBJECTIVES: To develop a
      quantitative method to support the process of selecting priority groups for
      public health interventions based on both high risk and population health burden.
      DESIGN: Secondary data analysis of the 2010 Canadian Community Health Survey.
      SETTING: Canadian population. PARTICIPANTS: Survey respondents. METHODS: We
      identified priority groups for 3 diseases: heart disease, stroke, and chronic
      lower respiratory diseases. Three measures--prevalence, population counts, and
      adjusted odds ratios (OR)--were calculated for subpopulations (sociodemographic
      characteristics and other risk factors). A Priority Group Index (PGI) was
      calculated by summing the rank scores of these 3 measures. RESULTS: Of the 30
      priority groups identified by the PGI (10 for each of the 3 disease outcomes), 7
      were identified on the basis of high prevalence only, 5 based on population count
      only, 3 based on high OR only, and the remainder based on combinations of these.
      The identified priority groups were all in line with the literature as risk
      factors for the 3 diseases, such as elderly people for heart disease and stroke
      and those with low income for chronic lower respiratory diseases. The PGI was
      thus able to balance both high risk and population burden approaches in selecting
      priority groups, and thus it would address health inequities as well as disease
      burden in the overall population. CONCLUSIONS: The PGI is a quantitative method
      to select priority groups for public health interventions; it has the potential
      to enhance the effective use of limited public resources.

PMID- 24463300
TI  - Modern management of Merkel cell carcinoma.
AB  - PURPOSE OF REVIEW: Merkel cell carcinoma (MCC) is a rare, aggressive malignancy.
      Worldwide incidence is increasing and roughly 50% of patients present with a
      primary lesion in the head and neck. This article discusses recent advances and
      treatment recommendations. RECENT FINDINGS: Recent research has focused on the
      carcinogenesis of MCC, in particular the role of Merkel cell polyoma virus
      (MCPyV) and its surrogate marker large T-antigen. Together with cytokeratin 20
      (CK20), other biomarkers like human insulin gene enhancer-binding protein islet-1
      (ISL1) and transcription factor OCT4 may provide improved methods for diagnosis
      and ultimately, therapy. SUMMARY: This review summarizes recent findings on MCC
      pathogenesis with a special emphasis on the impact of MCPyV. It further presents
      an overview of clinical aspects, and discusses treatment standards and emerging
      perspectives.

PMID- 24463301
TI  - The concept of symptomatic epilepsy and the complexities of assigning cause in
      epilepsy.
AB  - The concept of symptomatic epilepsy and the difficulties in assigning cause in
      epilepsy are described. A historical review is given, emphasizing aspects of the
      history which are relevant today. The historical review is divided into three
      approximately semicentenial periods (1860-1910, 1910-1960, 1960-present). A
      definition of symptomatic epilepsy and this is followed by listing of causes of
      symptomatic epilepsy. The fact that not all the causes of idiopathic epilepsy are
      genetic is discussed. A category of provoked epilepsy is proposed. The
      complexities in assigning cause include the following: the multifactorial nature
      of epilepsy, the distinction between remote and proximate causes, the role of
      nongenetic factors in idiopathic epilepsy, the role of investigation in
      determining the range of causes, the fact that not all symptomatic epilepsy is
      acquired, the nosological position of provoked epilepsy and the view of epilepsy
      as a process, and the differentiation of new-onset and established epilepsy. The
      newly proposed ILAE classification of epilepsy and its changes in terminologies
      and the difficulties in the concept of acute symptomatic epilepsy are discussed,
      including the inconsistencies and gray areas and the distinction between
      idiopathic, symptomatic, and provoked epilepsies. Points to be considered in
      future work are listed. 

PMID- 24463302
TI  - Effects of seizure severity and seizure freedom on the health-related quality of
      life of an African population of people with epilepsy.
AB  - PURPOSE: This study aimed at determining the effects of seizure severity and
      seizure freedom on health-related quality of life (HRQOL) of people with epilepsy
      (PWE) in the presence of perceived stigma in a sub-Saharan African culture.
      METHODS: Health-related quality of life was assessed using QOLIE-31 in 93
      consecutive adults (56 males and 37 females) with epilepsy. They were stratified
      into seizure-free, low-moderate seizure severity, and high seizure severity
      groups based on the seizure type and the number of seizures in the previous
      6months. Other illness variables and sociodemographic variables were also
      obtained. A 3-item perceived stigma scale was administered. A modified QOLIE-31
      (excluding the epilepsy-specific items) was given to 102 age- and sex-matched
      healthy controls. RESULTS: There was moderate negative correlation between
      seizure severity and mean total HRQOL score as well as scores on the Seizure
      Worry (p=.000), Overall Quality of Life (p=.000), and Social Function (p=.001)
      subscales of QOLIE-31. Overall, the healthy control subjects had a higher mean
      HRQOL score compared with the PWE put together (71.0+11.1 vs 64.2+/-13.6,
      p=.001). However, there was no difference in the mean HRQOL score between the
      seizure-free individuals and the healthy controls (p=.270). Seizure severity was
      associated with HRQOL independent of perceived stigma on a multiple regression
      analysis. CONCLUSION: This study provides evidence that seizure severity relates
      to health-related quality of life in an inverse, graded manner and independent of
      perceived stigma. Seizure-free people with epilepsy can have quality of life
      comparable with healthy individuals.

PMID- 24463303
TI  - Common comorbidities in women and men with epilepsy and the relationship between
      number of comorbidities and health plan paid costs in 2010.
AB  - The objectives of this observational study were to determine the prevalence of
      the most common comorbidities in women and men with epilepsy and to demonstrate
      the relationship of these comorbidities to health plan paid costs. Data for 6621
      members with epilepsy (52% women, 48% men) from eight commercial health plans
      were analyzed. The presence of comorbidities in people with epilepsy was
      identified by searching health insurance claims for 29 prespecified comorbidity
      specific diagnosis codes. More women (50%) than men (43%) with epilepsy had one
      or more of the 29 comorbidities (p<0.05). The top 10 comorbidities for women and
      their relative prevalences were psychiatric diagnosis (16%), hypertension (12%),
      asthma (11%), hyperlipidemia (11%), headache (7%), diabetes (6%), urinary tract
      infection (5%), hypothyroidism (5%), anemia (5%), and migraine (4%). For men, the
      top 10 comorbidities and their relative prevalences were psychiatric diagnosis
      (15%), hyperlipidemia (12%), hypertension (12%), asthma (8%), diabetes (5%),
      headache (4%), cancer (4%), coronary artery disease (3%), anemia (3%), and
      gastroesophageal reflux disease (3%). Seven of the top 10 comorbidities were
      common to both women and men. Psychiatric diagnosis was the only comorbidity
      among the top five comorbidities for all age groups. The presence of one
      comorbidity approximately tripled the health-care cost for that member compared
      with the cost for members who had no comorbidities. Additional comorbidities
      generally further increased costs. The increase in health-care cost per member
      per month ($) with increase in number of comorbidities was greater for men than
      for women (p<0.05). 

PMID- 24463304
TI  - The impact on family scale: psychometric analysis of long and short forms in
      parents of children with epilepsy.
AB  - Epilepsy in a child or adolescent can have severe psychosocial impact on the
      whole family and burdens them, especially the parents. As the familial background
      is essential for the child's coping and the progression of the epilepsy, parental
      burden should be considered within a comprehensive treatment approach. This study
      validated the applicability of the Impact on Family Scale (IOFS), a well
      established instrument that assesses the strains of families with chronically ill
      or disabled children, in parents of children with epilepsy. In a sample of 219
      parents, the psychometric properties of the original IOFS version (33 items) and
      two short forms (15 and 11 items, respectively) were examined. Both short forms
      revealed good reliability (Cronbach's alpha, test-retest reliability), and
      construct validity was verified by correlations with epilepsy- and burden-related
      variables. However, exploratory and confirmatory factor analyses indicated
      superior characteristics of the short form with 11 items (IOFS-11). In
      conclusion, the IOFS-11 as well as the IOFS-15 proved to be practicable,
      reliable, and valid tools to assess the impact of childhood epilepsy on family
      life in research and clinical practice. 

PMID- 24463305
TI  - Labrador retrievers and SUDEP: a simple theory that may have important
      applications.

PMID- 24463306
TI  - Changes in psychiatric comorbidity during early postsurgical period in patients
      operated for medically refractory epilepsy--a MINI-based follow-up study.
AB  - PURPOSE: The purpose of this study was to assess axis-I DSM-IV psychiatric
      disorders in patients at baseline and 3 months after surgery for medically
      refractory temporal lobe epilepsy. METHOD: The Mini International
      Neuropsychiatric Interview (MINI) and Quality of Life in Epilepsy Inventory-10
      (QOLIE-10) were evaluated before and 3 months after surgery in 50 consecutive
      patients (21 females, 29 males) with medically refractory temporal lobe epilepsy
      (persistent seizures>2/month, despite treatment with >=2 appropriate drugs in
      adequate doses for >=2 years) who underwent surgery [anterior temporal lobectomy
      with amygdalo-hippocampectomy (for mesial temporal sclerosis in 40),
      electrocorticography-guided lesionectomy (for other lesions in 10)]. RESULTS:
      Twenty-six patients (52%) had an axis-I psychiatric disorder [26% depressive
      disorder, 28% anxiety disorder] at baseline, while 30 (60%) patients had an axis
      I psychiatric disorder [28% depressive disorder, 28% anxiety disorder] at 3
      months after surgery. Twenty percent developed a new psychiatric disorder, while
      12% showed improvement postsurgery. Mean QOLIE-10 scores improved from 23.78 to
      17.80 [24 (48%) patients showed >=5-point improvement]. Thirty-four (68%)
      patients had no seizure, 6 (12%) had non-disabling seizures, while 2 (4%) had
      disabling seizures after surgery. High frequency of seizures prior to surgery
      (p<0.038) and seizure occurrence after surgery (p<0.055) predicted the presence
      of psychiatric disorders after surgery. No clinical characteristic could predict
      development of new psychiatric disorder after surgery. CONCLUSION: Psychiatric
      dysfunction in the early postsurgery period is seen in nearly half of patients
      undergoing surgery for temporal lobe epilepsy, is mild in nature, and does not
      adversely affect quality of life but may cause significant clinical problems when
      it arises de novo postsurgery.

PMID- 24463307
TI  - Prevalence and quality of anxiety in patients with epilepsy.
AB  - BACKGROUND: Depression and anxiety are the most frequent psychiatric disorders
      identified in patients with epilepsy. We aimed to determine the prevalence of
      state and trait anxiety in patients with epilepsy compared with people without
      epilepsy. METHODS: We recruited patients and healthy controls in the outpatient
      neurology clinic of Kurdistan University of Medical Sciences, Iran, during 2011.
      Eighty-four patients with epilepsy and 168 healthy persons from relatives of the
      patients in the case group were recruited and filled out the inventory. The State
      Trait Anxiety Inventory (STAI) was used to measure anxiety. After selection of
      participants and neurological evaluation, all subjects were clinically
      interviewed at the outpatient clinic of neurology. Data were analyzed using SPSS
      software, version 16. Fisher's exact and chi-square tests were used for nominal
      variables, and the t-test was used for anxiety scores. RESULTS: The average ages
      of the patients in the case and control groups were 28 and 27.5 years,
      respectively. State anxiety was significantly higher in patients with epilepsy
      than in the control group (p=0.042). Also, a higher trait anxiety score was
      reported in the case group compared with the control group (p=0.009). CONCLUSION:
      The rates of both state and trait anxiety were higher in patients in the case
      group. It appears that anxiety in epilepsy is not just a reaction to a stressful
      situation, and there may be genetic or temperamental factors that contribute to
      the relationship between epilepsy and anxiety.

PMID- 24463308
TI  - Discussing sudden unexpected death in epilepsy (SUDEP) with patients: practices
      of health-care providers.
AB  - There is a lack of consensus regarding how health-care providers should address
      SUDEP with patients. The purpose of this study was to describe various health
      care providers' practices regarding discussion of SUDEP with patients. Separate
      focus groups were conducted with epileptologists, neurologists, and advanced
      practice nurses. Across all disciplines, reasons for discussing SUDEP included
      Practical Accountability, Moral Accountability, Proactivity, and Reactivity. For
      nurses only, an additional reason was Patient Advocacy. In terms of when not to
      discuss SUDEP, for all disciplines, and especially the physicians, the theme Not
      at First emerged. Additional themes that emerged for this question included, in
      the case of neurologists and epileptologists, Moral Accountability and Out of
      Options. Ways in which SUDEP is discussed included, in all groups, Discussion and
      Written Materials. In addition, prevalent in all groups was the finding that
      procedures for discussing SUDEP with patients and families need to be somewhat
      standardized. Implications for practice are discussed. 

PMID- 24463309
TI  - Cerebral lateralization for language in deaf children with cochlear implantation.
AB  - Functional Transcranial Doppler ultrasonography (fTCD) was used to investigate
      the effects of early acoustic deprivation and subsequent reafferentation on
      cerebral dominance for language in deaf children provided with Cochlear
      Implantation (CI). Twenty children with CI (13 in right ear and 7 in left ear)
      and 20 controls matched for age, sex and handedness were administered a fTCD
      animation description task. Left hemisphere dominance for language with
      comparable mean Laterality Indexes (LIs) was found in children with CI and
      controls; right-ear implanted subjects showed cerebral activation controlateral
      to implanted ear more frequently than left-ear implanted ones. Linguistic
      proficiency of CI recipients was below age expectation in comparison to controls;
      language scores did not significantly differ between children with left and right
      LI, whereas both age and side of implantation were significantly related to
      language outcome. Theoretical implication and potential clinical application of
      fTCD in CI management are discussed. 

PMID- 24463311
TI  - Current views of hormone therapy for the management and treatment of
      postmenopausal women.

PMID- 24463310
TI  - Reading faces: investigating the use of a novel face-based orthography in
      acquired alexia.
AB  - Skilled visual word recognition is thought to rely upon a particular region
      within the left fusiform gyrus, the visual word form area (VWFA). We investigated
      whether an individual (AA1) with pure alexia resulting from acquired damage to
      the VWFA territory could learn an alphabetic "FaceFont" orthography, in which
      faces rather than typical letter-like units are used to represent phonemes.
      FaceFont was designed to distinguish between perceptual versus phonological
      influences on the VWFA. AA1 was unable to learn more than five face-phoneme
      mappings, performing well below that of controls. AA1 succeeded, however, in
      learning and using a proto-syllabary comprising 15 face-syllable mappings. These
      results suggest that the VWFA provides a "linguistic bridge" into left hemisphere
      speech and language regions, irrespective of the perceptual characteristics of a
      written language. They also suggest that some individuals may be able to acquire
      a non-alphabetic writing system more readily than an alphabetic writing system. 

PMID- 24463312
TI  - Molecular cloning of manganese superoxide dismutase gene in the cladoceran
      Daphnia magna: effects of microcystin, nitrite, and cadmium on gene expression
      profiles.
AB  - Superoxide dismutases (SODs) are metalloenzymes that represent one important line
      of defense against oxidative stress produced by reactive oxygen species in
      aerobic organisms. Generally, waterborne pollutants caused by irregular
      anthropogenic activities often result in oxidative damage in aquatic organisms.
      The aim of this study was to molecularly characterize the manganese superoxide
      dismutase gene (Dm-MnSOD) in the waterflea, Daphnia magna, and evaluate the mRNA
      expression patterns quantified by real-time PCR after exposure to three common
      waterborne pollutants (microcystin-LR, nitrite, and cadmium). The results showed
      that the full-length Dm-MnSOD sequence consists of 954 bp nucleotides, encoding
      215 amino acids, showing well-conserved domains that are required for metal
      binding and several common characteristics, such as two MnSOD domains. The
      deduced amino acid sequence of Dm-MnSOD shared over 70% similarity with
      homologues from Bythograea thermydron, Dromia personata, Cancer pagurus, and
      Scylla paramamosain. Dm-MnSOD gene expression was up-regulated in response to
      exposure to the three chemicals tested. The overall results indicated that Dm
      MnSOD gene is an inducible gene and potential biomarker indicating these
      pollutants in the environment.

PMID- 24463313
TI  - Pellino protein from pacific white shrimp Litopenaeus vannamei positively
      regulates NF-kappaB activation.
AB  - Pellino, named after its property that binds Pelle (the Drosophila melanogaster
      homolog of IRAK1), is a highly conserved E3 class ubiquitin ligase in both
      vertebrates and invertebrates. Pellino interacts with phosphorylated IRAK1,
      causing polyubiquitination of IRAK1, and plays a critical upstream role in the
      toll-like receptor (TLR) pathway. In this study, we firstly cloned and identified
      a crustacean Pellino from pacific white shrimp Litopenaeus vannamei (LvPellino).
      LvPellino contains a putative N-terminal forkhead-associated (FHA) domain and a C
      terminal ring finger (RING) domain with a potential E3 ubiquitin-protein ligase
      activity, and shows a high similarity with D. melanogaster Pellino. LvPellino
      could interact with L. vannamei Pelle (LvPelle) and over-expression of LvPellino
      could increase the activity of LvDorsal (a L. vannamei homolog of NF-kappaB) on
      promoters containing NF-kappaB binding motifs and enhance the expression of
      arthropod antimicrobial peptides (AMPs). The LvPellino protein was located in the
      cytoplasm and nucleus and LvPellino mRNA was detected in all the tissues examined
      and could be up-regulated after lipopolysaccharides, white spot syndrome virus
      (WSSV), Vibrio parahaemolyticus, and Staphylococcus aureus challenges, suggesting
      a stimulation response of LvPellino to bacterial and immune stimulant challenges.
      Knockdown of LvPellino in vivo could significantly decrease the expression of
      AMPs and increase the mortality of shrimps caused by V. parahaemolyticus
      challenge. However, suppression of the LvPellino expression could not change the
      mortality caused by WSSV infection, and dual-luciferase reporter assays
      demonstrated that over-expression of LvPellino could enhance the promoters of
      WSSV genes wsv069 (ie1), wsv303, and wsv371, indicating a complex role of
      LvPellino in WSSV pathogenesis and shrimp antiviral mechanisms.

PMID- 24463314
TI  - Knockdown of PU.1 mRNA and AS lncRNA regulates expression of immune-related genes
      in zebrafish Danio rerio.
AB  - The transcription factor PU.1 plays a key role in the development of immune
      system. Recent evidence demonstrated bidirectional transcription and a
      sense/antisense transcriptional regulatory manner in PU.1 locus. However, the
      effect of PU.1 mRNA and its antisense long non-coding RNA (AS lncRNA) on adaptive
      immunity in vivo is still not clear. In this study, we first confirmed the
      expression of PU.1 AS lncRNA by strand-specific RT-PCR in zebrafish.
      Additionally, we found that GFP was detected in zebrafish kidney using tissue
      smears after zebrafish was intraperitoneally injected with pLentiHI-PU.1 shRNA or
      pLentiHI-PU.1 AS shRNA for 2 days. Moreover, on day 0, 2 and 4, the levels of
      PU.1 and immune-related genes including TCRAC, Rag2, AID, IgLC-1, mIg, and sIg
      mRNAs were detected using real-time qPCR. The results showed that the levels of
      PU.1 and above 6 immune-related gene mRNAs were significantly downregulated on
      day 2 (P<0.05) and day 4 (P<0.01) by the treatment with the pLentiHI-PU.1 shRNA,
      whereas these genes were markedly upregulated by the treatment with the pLentiHI
      PU.1 AS shRNA. Based on our results, we suggested that the effects of PU.1
      transcripts including mRNA and AS lncRNA on immune-related gene expression in
      zebrafish were opposite. To our knowledge, this was the first report that a novel
      functional AS lncRNA in adaptive immunity was transcribed from the zebrafish PU.1
      locus. Our findings provided novel insight into further exploration on modulating
      adaptive immunity by regulating PU.1 mRNA and AS lncRNA.

PMID- 24463315
TI  - Developmentally regulated GTP-binding protein 2 ameliorates EAE by suppressing
      the development of TH17 cells.
AB  - Developmentally regulated GTP-binding protein 2 (DRG2) represents a novel
      subclass of GTP-binding proteins. We here report that transgenic overexpression
      of DRG2 in mice ameliorates experimental autoimmune encephalomyelitis (EAE), a
      murine model of multiple sclerosis (MS). The protective effect of DRG2 in EAE was
      mediated by the inhibition of the development of T(H)17 cells. DRG2 enhanced the
      activity of PPARgamma, which led to an inhibition of the nuclear factor kappa B
      (NF-kappaB) activity and IL-6 production in antigen presenting cells and an
      inhibition of the development of T(H)17 cells. Our results demonstrate that DRG2
      is an essential modulator of EAE.

PMID- 24463316
TI  - The apoptotic pathways effect of fine particulate from cooking oil fumes in
      primary fetal alveolar type II epithelial cells.
AB  - Apoptosis occurs along three major pathways: (i) an extrinsic pathway, mediated
      by death receptors; (ii) an intrinsic pathway centered on mitochondria; and (iii)
      an ER-stress pathway. We investigated the apoptotic pathway effects of cooking
      oil fumes (COF) in fetal lung type II-like epithelium cells (AEC II). Exposure to
      COF caused up-regulation of the pro-apoptotic protein Bax and down-regulation of
      the anti-apoptotic protein Bcl-2. COF induced the mitochondrial permeability
      transition, an early event in apoptosis; cytochrome c was translocated from the
      mitochondria to the cytoplasm and nucleus. Caspase-9 and caspase-3 were
      activated, as a consequence of the mitochondrial permeability transition. The
      death receptor apoptotic pathway was triggered by COF, as indicated by a change
      in Fas expression, resulting in increased caspase-8 content. COF exposure
      arrested the cell cycle the at G0-G1 phase. In summary, COF can lead to apoptosis
      via mitochondrial and death receptor pathways in AEC II cells. 

PMID- 24463317
TI  - Visual ergonomics at work and leisure.

PMID- 24463318
TI  - Vision, light and aging: a literature overview on older-age workers.
AB  - BACKGROUND: In many western countries individuals will need to continue their
      professional careers beyond the current retirement age. This requires adaptation
      of the working conditions to compensate for age related visual changes.
      OBJECTIVE: The aim of this paper is to compile and structure knowledge concerning
      age related changes in visual and non-visual functions among older-age workers
      and to describe in what way these changes relate to light and work performance.
      METHOD: An overview of the literature was performed in PubMed and EMBASE
      concerning visual changes among elderly people, light, visual ergonomics and
      consequences at work. RESULTS: Visual conditions and lighting design have an
      impact on work performance in those over age 65 even if there are few studies
      available. Natural age related changes in the eyes or ocular diseases can result
      in reduced visual function and performance. Moreover, evidence of the importance
      of light and dark rhythms for circadian regulation is mounting; there are
      indications that the older-age population might need specific attention related
      to this issue. Finally, visual deteriorations might also, secondarily, induce
      strained postures and musculoskeletal symptoms, pain and injury. CONCLUSION: Age
      related changes in the eyes and also ocular diseases among older-age people have
      an impact on well-being and work performance, and therefore call for
      reconsideration of their working conditions. Knowledge about how visual
      functions, light and ocular diseases is needed for work design and preventive
      actions.

PMID- 24463319
TI  - [200 years of the Thurgau Veterinary Society].

PMID- 24463320
TI  - [Helminth control in the adult horse: the need for a re-orientation].
AB  - The epidemiological situation of strongyle infections in adult horses in
      Switzerland is characterized by a strong dominance of small strongyles
      (Cyathostominae) and an overall low level of egg shedding in the faeces. The
      prevailing attitude towards anthelmintic therapy considers neither husbandry
      conditions nor pasture hygiene measures. Instead, calendar-based routine
      medication, comprising usually 3 to 4 annual treatments, is the typical strategy.
      Such an approach, however, often results in an excessive administration of
      anthelmintics. With respect to the continuous spread of drug resistant
      cyathostomins a change of strategy seems inevitable. A consensus has been agreed
      on between equine parasitologists and clinicians of the Vetsuisse Faculty in
      Zurich and Berne to focus on the concept of a selective control approach, based
      on individual faecal egg counts as the central element. It is now recommended
      that clinically healthy horses (> 4 y) are treated only when their strongyle egg
      count is equal to or higher than 200 eggs per gram of faeces. A regular analysis
      of the strongyle population based on larval cultures, the control of drug
      efficacy, and quarantine measures for incoming horses are mandatory components of
      the concept. Recent experiences in several pilot farms have indicated that only 4
      % of the McMaster analyses resulted in a deworming treatment. For horses that did
      not receive any nematicidal anthelmintic during the current season, a "safety"
      treatment is recommended at the end of the grazing period. 

PMID- 24463321
TI  - Lameness and foot lesions in Swiss dairy cows: I. Prevalence.
AB  - Prevalences of foot lesions and lameness were recorded in 1'449 Swiss dairy cows
      during routine claw-trimming on 78 farms from June 2010 until February 2011.
      Lameness was present in 14.8 % of cows and on 80.8 % of investigated farms.
      Highest prevalences were seen for widened white line (80.7 %/100 %), signalling
      foot lesion (65.6 %/98.7 %), heel-horn erosion (34.2 %/88.5 %), digital
      dermatitis complex (29.1 %/73.1 %), severe hemorrhages (27.9 %/87.2 %), and
      Rusterholz' sole ulcers (11.5 %/74.4 %) at cow and herd level, respectively.
      Lower prevalences were found for subclinical laminitis (5.4 %/47.4 %), chronic
      laminitis (3.3 %/25.6 %), white line disease (4.7 %/42.3 %), double soles (2.6
      %/33.3 %), interdigital hyperplasia (3.1 %/33.3 %), sole ulcers (0.4 %/6.4 %),
      toe infections caused by faulty claw-trimming (3.9 %/39.7 %) and by injury (0.1
      %/2.6 %), deep lacerations (0.4 %/6.4 %), and interdigital phlegmona (0.1 %/1.3
      %). Lameness and foot lesions were shown to represent important health problems
      of dairy cows under the conditions of the typical grass-based production system
      in Switzerland. Digital dermatitis has developed to the most relevant foot
      disease with a high impact on welfare of Swiss dairy cows within the past 10
      years. 

PMID- 24463322
TI  - Lameness and foot lesions in Swiss dairy cows: II. Risk factors.
AB  - The objective of this study was to evaluate risk factors associated with foot
      lesions and lameness in Swiss dairy cows. Potential risk factors were recorded by
      means of examination of 1'449 Swiss cows and the management systems of 78 farms
      during routine claw-trimming, and during personal interviews with the associated
      farmers. Statistical analysis of animal-based and herd level risk factors were
      performed using multivariate logistic regression models. The risk of being lame
      was increased in cows affected by digital dermatitis complex, heel-horn erosion,
      interdigital hyperplasia, Rusterholz' sole ulcer, deep laceration, double sole
      and severe hemorrhages. Cleanliness, BCS, affection with other foot lesions,
      breed, importance of claw health to the farmer, frequency of routine claw
      trimming, producing according to the guidelines of the welfare label program
      RAUS, and silage feeding were shown to be associated with the occurrence of some
      of the evaluated foot lesions and lameness. The identified risk factors may help
      to improve management and the situation of lameness and claw health in dairy cows
      in Switzerland and other alpine areas with similar housing and pasturing systems.

PMID- 24463323
TI  - Use of nitinol self-expandable stents in 26 dogs with tracheal collapse.
AB  - A study was designed to describe a novel approach to the treatment of tracheal
      collapse (TC) in dogs using self-expandable nitinol stents. Medical records were
      reviewed retrospectively for 26 client owned dogs in which nitinol stents were
      deployed. The entire length of trachea was supported independently of the extent
      of TC. Two overlapping stents were used instead of one in cases where one stent
      was not spanning the entire trachea adequately. The diameter of the cranial
      radiolucent portion of trachea, just behind the cricoid cartilage, was measured
      as a specific landmark to select the appropriate size of the stent. Two self
      expandable nitinol stents were inserted in 9 of 26 dogs; the trachea in the rest
      of the cases was supported with only one stent. A follow up tracheoscopy was
      performed in 10 of 26 cases with recurrent clinical signs. Secondary tracheal
      stenosis in these cases was caused by stent fracture, granuloma or excessive
      stent shortening. Additional stents were placed successfully to expand the
      stenotic lumen. A support of the entire trachea may decrease risk of nitinol
      fracture at the end of the implant. Long term clinical improvement (25 of 26
      dogs, 96 %) is comparable with the results of other studies. 

PMID- 24463327
TI  - Impact of including readmissions for qualifying events in the patient safety
      indicators.
AB  - The Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs)
      do not capture complications arising after discharge. This study sought to
      quantify the bias related to omission of readmissions for PSI-qualifying
      conditions. Using 2000-2009 California Office of Statewide Health Planning and
      Development Patient Discharge Data, the study team examined the change in PSI
      rates when including readmissions in the numerator, hospitals performing in the
      extreme deciles, and longitudinal performance. Including 7-day readmissions
      resulted in a 0.3% to 8.9% increase in average hospital PSI rates. Hospital PSI
      rates with and without PSI-qualifying 30-day readmissions were highly correlated
      for point estimates and within-hospital longitudinal change. Most hospitals
      remained in the same relative performance decile. Longer length of stay, public
      payer, and discharge to skilled nursing facilities were associated with a higher
      risk of readmission for a PSI-qualifying event. Failure to include readmissions
      in calculating PSIs is unlikely to lead to erroneous conclusions. 

PMID- 24463328
TI  - Association between patient satisfaction and outcomes in kidney transplant.
AB  - This was a cross-sectional cohort study analyzing aggregate publicly reported
      data integrated from 2 primary sources and included all US accredited kidney
      transplant programs that report data within the Scientific Registry of Transplant
      Recipients and Hospital Compare; 188 kidney transplant programs, representing 15
      710 transplants were included in this study. In general, the scores for patient
      satisfaction questions were higher for higher-performing transplant programs; 5
      questions reached statistically significant associations (P < .05). A composite
      of these 5 questions demonstrated a strong association with a center's
      performance indices for both 1-month and 1-year graft and patient outcomes (69%
      vs 40%, P < .001, and 60% vs 44%, P = .035, respectively), which remained
      significant after controlling for baseline demographics. The results demonstrate
      that there is a positive and statistically significant correlation between a
      patient's perceived quality of care, as measured by HCAHPS data, and quantified
      clinical outcomes for graft loss and patient death in kidney transplant
      recipients. 

PMID- 24463329
TI  - Multiplexing signals in reinforcement learning with internal models and dopamine.
AB  - A fundamental challenge for computational and cognitive neuroscience is to
      understand how reward-based learning and decision-making are made and how accrued
      knowledge and internal models of the environment are incorporated. Remarkable
      progress has been made in the field, guided by the midbrain dopamine reward
      prediction error hypothesis and the underlying reinforcement learning framework,
      which does not involve internal models ('model-free'). Recent studies, however,
      have begun not only to address more complex decision-making processes that are
      integrated with model-free decision-making, but also to include internal models
      about environmental reward structures and the minds of other agents, including
      model-based reinforcement learning and using generalized prediction errors. Even
      dopamine, a classic model-free signal, may work as multiplexed signals using
      model-based information and contribute to representational learning of reward
      structure.

PMID- 24463330
TI  - Bayesian statistics: relevant for the brain?
AB  - Analyzing data from experiments involves variables that we neuroscientists are
      uncertain about. Efficiently calculating with such variables usually requires
      Bayesian statistics. As it is crucial when analyzing complex data, it seems
      natural that the brain would "use" such statistics to analyze data from the
      world. And indeed, recent studies in the areas of perception, action, and
      cognition suggest that Bayesian behavior is widespread, in many modalities and
      species. Consequently, many models have suggested that the brain is built on
      simple Bayesian principles. While the brain's code is probably not actually
      simple, I believe that Bayesian principles will facilitate the construction of
      faithful models of the brain. 

PMID- 24463331
TI  - Induction of innate immune signatures following polyepitope protein-glycoprotein
      B-TLR4&9 agonist immunization generates multifunctional CMV-specific cellular and
      humoral immunity.
AB  - Recent studies have suggested that a successful subunit human cytomegalovirus
      (CMV) vaccine requires improved formulation to generate broad-based anti-viral
      immunity following immunization. Here we report the development of a non-live
      protein-based vaccine strategy for CMV based on a polyepitope protein and CMV
      glycoprotein B (gB) adjuvanted with TLR4 and/or TLR9 agonists. The polyepitope
      protein includes contiguous multiple MHC class I-restricted epitopes with an aim
      to induce CD8(+) T cell immunity, while gB is an important target for CD4(+) T
      cell immunity and neutralizing antibodies. Optimal immunogenicity of this
      bivalent non-live protein vaccine formulation was dependent upon the co
      administration of both the TLR4 and TLR9 agonist, which was associated with the
      activation of innate immune signatures and the influx of different DC subsets
      including plasmacytoid DCs and migratory CD8-DEC205+CD103-CD326- langerin
      negative dermal DCs into the draining lymph nodes. Furthermore these professional
      antigen presenting cells also expressed IL-6, IL-12p70, TNFalpha, and IFNalpha
      which play a crucial role in the activation of adaptive immunity. In summary,
      this study provides a novel platform technology in which broad-based anti-CMV
      immune responses upon vaccination can be maximised by co-delivery of viral
      antigens and TLR4 and 9 agonists which induce activation of innate immune
      signatures and promote potent antigen acquisition and cross-presentation by
      multiple DC subsets. 

PMID- 24463333
TI  - Insecticide-treated mosquito nets in rural Burkina Faso: assessment of coverage
      and equity in the wake of a universal distribution campaign.
AB  - Insecticide-treated mosquito nets (ITNs) are an essential tool of the Roll Back
      Malaria strategy. An increasing number of African countries have embarked on mass
      distribution campaigns of long-lasting insecticide-treated nets (LLINs) with the
      ultimate goal of universal coverage. Such a national campaign with the goal of
      one ITN for every two people has been conducted in Burkina Faso in 2010. Our aim
      was to assess the coverage and equity effect of the universal distribution
      campaign of LLINs in Burkina Faso and to identify determinants of ITN ownership
      across households after the campaign. We evaluated its effects through comparison
      of data from two household surveys conducted in early 2010 (before the campaign)
      and early 2011 (after the campaign) on a representative rural district in north
      western Burkina Faso. Data were collected on household characteristics (including
      socio-economic status) and ITN ownership. We used concentration curves and
      indices to compare ITN coverage indicators before and after the campaign and
      multilevel multivariate logistic regression to estimate factors associated with
      achievement of the universal coverage target in 2011. The survey included 1106
      households in 2010 and 1094 in 2011. We found that the proportion of households
      with at least one ITN increased from 59% before the campaign to 99% afterwards,
      whereas the concentration index dropped from 0.087 (standard error (SE): 0.014)
      to 0.002 (SE: 0.002). Fifty-two per cent of households reached the target of one
      ITN for every two people per household, with the relevant concentration index at 
      0.031 (SE: 0.016). Eighty-six per cent of households owned at least one ITN for
      every three people. The main characteristics significantly associated with the
      targeted intra-household coverage were family size and distance to the health
      centre but not socio-economic status. In conclusion, despite not having fully met
      its target, the national LLIN campaign achieved a high level of coverage and
      fostered equity. 

PMID- 24463332
TI  - Sorting out the trash: the spatial nature of eukaryotic protein quality control.
AB  - Failure to maintain protein homeostasis is associated with aggregation and cell
      death, and underies a growing list of pathologies including neurodegenerative
      diseases, aging, and cancer. Misfolded proteins can be toxic and interfere with
      normal cellular functions, particularly during proteotoxic stress. Accordingly,
      molecular chaperones, the ubiquitin-proteasome system (UPS) and autophagy
      together promote refolding or clearance of misfolded proteins. Here we discuss
      emerging evidence that the pathways of protein quality control (PQC) are
      intimately linked to cell architecture, and sequester proteins into spatially and
      functionally distinct PQC compartments. This sequestration serves a number of
      functions, including enhancing the efficiency of quality control; clearing the
      cellular milieu of potentially toxic species and facilitating asymmetric
      inheritance of damaged proteins to promote rejuvenation of daughter cells. 

PMID- 24463334
TI  - Can health workers reliably assess their own work? A test-retest study of bias
      among data collectors conducting a Lot Quality Assurance Sampling survey in
      Uganda.
AB  - BACKGROUND: Lot Quality Assurance Sampling (LQAS) is a classification method that
      enables local health staff to assess health programmes for which they are
      responsible. While LQAS has been favourably reviewed by the World Bank and World
      Health Organization (WHO), questions remain about whether using local health
      staff as data collectors can lead to biased data. METHODS: In this test-retest
      research, Pallisa Health District in Uganda is subdivided into four
      administrative units called supervision areas (SA). Data collectors from each SA
      conducted an LQAS survey. A week later, the data collectors were swapped to a
      different SA, outside their area of responsibility, to repeat the LQAS survey
      with the same respondents. The two data sets were analysed for agreement using
      Cohens' kappa coefficient and disagreements were analysed. RESULTS: Kappa values
      ranged from 0.19 to 0.97. On average, there was a moderate degree of agreement
      for knowledge indicators and a substantial level for practice indicators.
      Respondents were found to be systematically more knowledgeable on retest
      indicating bias favouring the retest, although no evidence of bias was found for
      practices indicators. CONCLUSIONS: In this initial study, using local health care
      providers to collect data did not bias data collection. The bias observed in the
      knowledge indicators is most likely due to the 'practice effect', whereby
      respondents increased their knowledge as a result of completing the first survey,
      as no corresponding effect was seen in the practices indicators.

PMID- 24463335
TI  - Leg skin stimulation can be a strategy to improve postural control in the
      elderly.
AB  - Previous studies suggested that skin stimulation by using medical tape glued to
      the skin over the Achilles tendon can improve postural control in young adults.
      Such strategy can be valuable if helping to improve postural control in the
      elderly. Here, we tested the effects of skin stimulation on the postural control
      of elderly while standing barefoot. Twenty-two voluntary elderly had postural
      control assessed under different conditions of skin stimulation. Center of
      pressure was monitored while they stood quietly barefoot on a force plate during
      standing with and without medical tape glued to the skin over the Achilles
      tendon. There were effects of skin stimulation for anteroposterior amplitude of
      center of pressure displacement, mediolateral amplitude of center of pressure
      displacement, and area of the ellipse for 95% of center of pressure data (P<.05).
      These results are promising considering that skin stimulation by using medical
      tape is feasible even for low incoming subjects and possible to self manage for
      improvements in postural control. 

PMID- 24463336
TI  - Association of interleukin-4 genetic polymorphisms with sporadic Alzheimer's
      disease in Chinese Han population.
AB  - Cytokine interleukin-4 (IL-4) is thought to play a role in the pathogenesis of
      Alzheimer's disease (AD). This study aimed to evaluate the potential association
      between single nucleotide polymorphisms (SNP) of IL-4 gene and AD susceptibility.
      This case-control study was conducted in Chinese Han populations consisting of
      203 AD patients and 205 controls. Three common SNPs of IL-4 gene, including 
      590C>T (rs2243250), -33C>T (rs2070874), and -1098T>G (rs2243248), were determined
      by the polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) and verified using DNA sequencing methods. Our data show that -590C and 
      1098G alleles of IL-4 were more common in AD patients (30.5% vs 22.2% p=0.007;
      14.3% vs 3.4% p<0.0001) and significantly associated with elevated risk for AD
      (OR=1.51 95% CI 1.05-2.23; OR=4.78 95% CI 2.37-7.67). Haplotype analysis revealed
      five common haplotypes CCG (OR=4.41), CCT (OR=1.22), TTT (OR=1.02), CTT (OR=0.7),
      and TCT (OR=0.14), from highest to lowest risk for AD. None of the associations
      appeared to be modified by APOE E4 genetic variant. Bioinformatic analysis shows
      that -590C>T and -1098T>G have a linkage disequilibrium (LD) with multiple
      potentially functional SNPs inside IL-4 gene. Our findings indicate that the 
      590C and -1098G alleles located in the promoter of IL-4 may increase the
      susceptibility to AD among the Han Chinese and might be used as molecular markers
      for AD risk evaluation. 

PMID- 24463337
TI  - Function-preserving reduction and fixation of unstable Jefferson fractures using
      a C1 posterior limited construct.
AB  - STUDY DESIGN: This is a retrospective, clinical, and radiologic study of
      posterior reduction and fusion of the C1 arch in the treatment of unstable
      Jefferson fractures. OBJECTIVE: The aim of the study was to describe a new motion
      preserving surgical technique in the treatment of unstable Jefferson fracture.
      SUMMARY OF BACKGROUND DATA: The management of unstable Jefferson fractures
      remains controversial. The majority of C1 fractures can be effectively treated
      nonoperatively with external immobilization unless there is an injury to the
      transverse atlantal ligament (TAL). Conservative treatment usually involves
      immobilization for a long time in Halo vest, whereas surgical intervention
      generally involves C1-C2 fusion, eliminating the range of motion of the upper
      cervical spine. We propose a novel method for the treatment of unstable Jefferson
      fractures without restricting the range of motion. METHODS: A retrospective
      review of 12 patients with unstable C1 fractures between April 2008 and October
      2011 was performed. They were treated by inserting bilateral posterior C1 pedicle
      screws or lateral mass screws interconnected by a transversal rod to achieve
      internal fixation. There were 8 men and 4 women, with an average age of 35.6
      years (range, 20-60 y). Presenting symptoms included neck pain, stiffness, and
      decreased range of motion but none had neurological injury. Seven patients had
      bilateral posterior arch fractures associated with unilateral anterior arch
      fractures (posterior 3/4 Jefferson fracture, Landells type II), and 5 had
      unilateral anterior and posterior arch fractures (half-ring Jefferson fracture,
      Landells type II). Seven patients had intact TAL, and 5 patients had fractures
      and avulsion of the attachment of TAL (Dickman type II). RESULTS: A total of 24
      screws were inserted. Five cases had screws placed in the lateral mass: 3 because
      of posterior arch breakage, and 2 because the height of the posterior arch at the
      entry point was <4 mm. The remaining 7 cases had pedicle screw fixation. One
      patient had venous plexus injury during exposure of lower margin of the posterior
      arch; however, successful hemostasis was achieved with Gelfoam. Postoperative x
      ray and computed tomography scan showed partial breach of the transverse foramen
      caused by a screw in 1 case, and breach of the inner cortex of the pedicle caused
      by screw displacement in 1 case; however, no spinal cord injury or vertebral
      artery injury was found. The remaining screws were in good position. Patients
      were followed up for 6-40 months (average, 22 mo). All cases had recovery of
      range of motion of the cervical spine to the preinjury level by 3-6 months after
      surgery, with resolution of pain. At 6 months follow-up, plain radiographs and
      computed tomography scans revealed satisfactory cervical alignment, no implant
      failure, and satisfactory bony fusion of the fractures; no C1-C2 instability was
      observed on the flexion-extension radiographs. CONCLUSIONS: C1 posterior limited
      construct is a valid technique and a feasible method for treating unstable
      Jefferson fractures, which allows preservation of the function of the
      craniocervical junction, without significant morbidity.

PMID- 24463338
TI  - The impact of object carriage on independent locomotion.
AB  - The current study examined whether carrying objects in one's hands influenced
      different parameters associated with independent locomotion. Specifically, 14-
      and 24-month-olds walked in a straight path under four conditions of object
      carriage - no object (control), one object carried in one hand (one object-one
      hand), two objects carried in each of the hands (two objects-two hands), and one
      object carried in both hands simultaneously (one object-two hands). Although
      carrying objects failed to influence a variety of kinematic parameters of gait,
      it did affect children's arm postures, with children adopting less mature arm
      positions when carrying objects. Finally, arm position was related to walking
      skill, but only for older children when they were not carrying objects. These
      findings indicate that although a relation does exist between arm positions and
      gait parameters, this relation is easily disrupted by carrying loads, even small
      ones. 

PMID- 24463339
TI  - Early interactive behaviours in preterm infants and their mothers: influences of
      maternal depressive symptomatology and neonatal birth weight.
AB  - The study evaluated the quality of preterm infant-mother interactions,
      considering severity of birth weight (ELBW and VLBW) and maternal depression,
      compared to full term babies. 69 preterm infants (29 ELBW and 40 VLBW) and 80
      full-term (FT) infants and their mothers were recruited. At 3 months of corrected
      age, the quality of mother-infant interaction was evaluated through Global Rating
      Scales; moreover, infant level of development and maternal depression were
      assessed through Griffith Development Mental Scales and Edinburgh Postnatal
      Depression Scale. Results showed adequate sensitivity in preterm infants' mothers
      and higher involvement with their infants, compared to full term mothers, but
      ELBW ones exhibited an intrusive interactive pattern and a higher prevalence of
      depressive symptoms. The study underlined the relevance of paying special
      attention to both ELBW infants and their mothers, in order to support the
      parenting role and the co-construction of early interactions. 

PMID- 24463340
TI  - Effects of pacemaker, implantable cardioverter-defibrillator, and left
      ventricular leads on CT-based attenuation correction.
AB  - CT-based attenuation correction (CTAC) of myocardial SPECT images has been
      becoming more popular--and the application of SPECT/CT increasing--because it
      prevents attenuation-induced image degradation. However, CTAC can be affected by
      overestimation of counts caused by metals. It is possible that pacemaker, left
      ventricle (LV), and implantable cardioverter-defibrillator (ICD) leads have an
      influence on myocardial SPECT findings. The present study investigated the impact
      of these leads on SPECT with CTAC. METHODS: Pacemaker, LV, and ICD leads were
      examined using a simple phantom and a cardiac phantom. The effects of metal
      artifacts from leads in high-resolution mode and ultra-high-resolution mode were
      assessed using a simple phantom. Images and polar maps were generated from the
      cardiac phantom. RESULTS: The pacemaker and LV leads essentially had no
      influence, whereas the ICD lead resulted in maximal (6%) overestimation in a
      study investigating which metals cause artifacts that affect CTAC. None of the
      leads seriously influenced CTAC when the cardiac phantom was used. CONCLUSION:
      Small pacemaker or ICD and LV leads will cause a slight overestimation, but CTAC
      should be used because it can correct attenuation of the inferior and
      anteroseptal walls on SPECT images.

PMID- 24463341
TI  - 111In-DTPA cisternography with SPECT/CT for the evaluation of normal pressure
      hydrocephalus.
AB  - Although new MR imaging techniques can provide high-resolution information on CSF
      dynamics and are not associated with ionizing radiation, SPECT/CT cisternography
      is a valuable alternative for those with contraindications to MR imaging.
      SPECT/CT cisternography combines functional and anatomic imaging to provide
      accurate and detailed information on CSF distribution to be used in conjunction
      with clinical findings for the diagnosis and evaluation of NPH, as illustrated in
      this case report. 

PMID- 24463342
TI  - From single target to multitarget/network therapeutics in Alzheimer's therapy.
AB  - Brain network dysfunction in Alzheimer's disease (AD) involves many proteins
      (enzymes), processes and pathways, which overlap and influence one another in AD
      pathogenesis. This complexity challenges the dominant paradigm in drug discovery
      or a single-target drug for a single mechanism. Although this paradigm has
      achieved considerable success in some particular diseases, it has failed to
      provide effective approaches to AD therapy. Network medicines may offer
      alternative hope for effective treatment of AD and other complex diseases. In
      contrast to the single-target drug approach, network medicines employ a holistic
      approach to restore network dysfunction by simultaneously targeting key
      components in disease networks. In this paper, we explore several drugs either in
      the clinic or under development for AD therapy in term of their design
      strategies, diverse mechanisms of action and disease-modifying potential. These
      drugs act as multi-target ligands and may serve as leads for further development
      as network medicines. 

PMID- 24463343
TI  - Mercury-supported biomimetic membranes for the investigation of antimicrobial
      peptides.
AB  - Tethered bilayer lipid membranes (tBLMs) consist of a lipid bilayer interposed
      between an aqueous solution and a hydrophilic "spacer" anchored to a gold or
      mercury electrode. There is great potential for application of these biomimetic
      membranes for the elucidation of structure-function relationships of membrane
      peptides and proteins. A drawback in the use of mercury-supported tBLMs with
      respect to gold-supported ones is represented by the difficulty in applying
      surface sensitive, spectroscopic and scanning probe microscopic techniques to
      gather information on the architecture of these biomimetic membranes.
      Nonetheless, mercury-supported tBLMs are definitely superior to gold-supported
      biomimetic membranes for the investigation of the function of membrane peptides
      and proteins, thanks to a fluidity and lipid lateral mobility comparable with
      those of bilayer lipid membranes interposed between two aqueous phases (BLMs),
      but with a much higher robustness and resistance to electric fields. The
      different features of mercury-supported tBLMs reconstituted with functionally
      active membrane proteins and peptides of bacteriological or pharmacological
      interest may be disclosed by a judicious choice of the most appropriate
      electrochemical techniques. We will describe the way in which electrochemical
      impedance spectroscopy, potential-step chronocoulometry, cyclic voltammetry and
      phase-sensitive AC voltammetry are conveniently employed to investigate the
      structure of mercury-supported tBLMs and the mode of interaction of antimicrobial
      peptides reconstituted into them. 

PMID- 24463344
TI  - Ultrasound mediated transdermal drug delivery.
AB  - Transdermal drug delivery offers an attractive alternative to the conventional
      drug delivery methods of oral administration and injections. However, the stratum
      corneum serves as a barrier that limits the penetration of substances to the
      skin. Application of ultrasound (US) irradiation to the skin increases its
      permeability (sonophoresis) and enables the delivery of various substances into
      and through the skin. This review presents the main findings in the field of
      sonophoresis in transdermal drug delivery as well as transdermal monitoring and
      the mathematical models associated with this field. Particular attention is paid
      to the proposed enhancement mechanisms and future trends in the fields of
      cutaneous vaccination and gene therapy. 

PMID- 24463345
TI  - Magnetic resonance guided high-intensity focused ultrasound for image-guided
      temperature-induced drug delivery.
AB  - Magnetic resonance guided high-intensity focused ultrasound (MR-HIFU) is a
      versatile technology platform for noninvasive thermal therapies in oncology.
      Since MR-HIFU allows heating of deep-seated tissue to well-defined temperatures
      under MR image guidance, this novel technology has great potential for local heat
      mediated drug delivery from temperature-sensitive liposomes (TSLs). In
      particular, MR provides the ability for image guidance of the drug delivery when
      an MRI contrast agent is co-encapsulated with the drug in the aqueous lumen of
      the liposomes. Monitoring of the tumor drug coverage offers possibilities for a
      personalized thermal treatment in oncology. This review focuses on MR-HIFU as a
      noninvasive technology platform, temperature-sensitive liposomal formulations for
      drug delivery and image-guided drug delivery, and the effect of HIFU-induced
      hyperthermia on the TSL and drug distribution. Finally, the opportunities and
      challenges of localized MR-HIFU-mediated drug delivery from temperature-sensitive
      liposomes in oncology are discussed. 

PMID- 24463346
TI  - The clinical relevance of KRAS gene mutation in non-small-cell lung cancer.
AB  - PURPOSE OF REVIEW: There are conflicting data on the potential prognostic and
      predictive role of mutant KRAS in non-small-cell lung cancer (NSCLC). RECENT
      FINDINGS: KRAS is the most frequently mutated oncogene in lung adenocarcinoma
      patients of non-Asian ethnicity. Novel data also revealed that allelic variants
      of mutant KRAS are different concerning their biochemistry, which may influence
      their prognostic and predictive role in NSCLC. Though mutant KRAS is not the
      target of molecular therapy yet, a molecular diagnostic algorithm involving KRAS
      determination can define a subgroup of tumors where no further diagnostic test is
      necessary due to the exclusivity of this driver oncogene mutation. Recent data
      indicated that the prognostic role of mutant KRAS in lung adenocarcinomas in
      Asian patients is evident, while more research is neccessary in non-Asian
      populations. Studies also suggest the potential predictive role of mutant KRAS in
      the context of chemosensitivity of NSCLC which may depend on the individual drug
      types. Recent data on the negative predictive role of KRAS mutation on the
      efficacy of EGFR tyrosine kinase inhibitor (TKI) therapies confirm previous
      findings. SUMMARY: Studies on the prognostic and predictive role of mutant KRAS
      in lung adenocarcinoma must be extended to the analysis of the potential role for
      allelic variants.

PMID- 24463347
TI  - Recent advances in primary cutaneous B-cell lymphomas.
AB  - PURPOSE OF REVIEW: In the last decade, there has been considerable debate
      regarding the classification and terminology of the group of primary cutaneous B
      cell lymphomas (CBCLs). With the introduction of the WHO-EORTC classification for
      cutaneous lymphomas, three main types of CBCLs are recognized: primary cutaneous
      marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma
      (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCLBCL, LT).
      RECENT FINDINGS: Epidemiological studies performed on different patient cohorts
      showed that the CBCL entities described in the WHO-EORTC classification and the
      4th WHO classification of tumours of haematopoietic and lymphoid tissues are
      reproducible worldwide and are clinically relevant, thereby illustrating the
      clinical usefulness of the WHO-EORTC classification. Furthermore, collaborative
      studies between the ISCL and EORTC lymphoma group resulted in recommended staging
      procedures and consensus treatment recommendations for different CBCL subtypes.
      SUMMARY: The advances in the classification, staging procedures and treatment of
      CBCLs have led to a major improvement in clinical care. The progress in CBCL
      classification enables molecular studies on well defined groups of patients and
      facilitates comparison of treatment results between different centres. Recent
      studies found that intralesional/intravenous rituximab has a therapeutic value in
      PCFCL and PCMZL with widespread cutaneous lesions and suggest that therapies
      targeting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF
      kB) pathway could be helpful in DLBCL, LT.

PMID- 24463348
TI  - Heat shock protein 90 inhibitors in non-small-cell lung cancer.
AB  - PURPOSE OF REVIEW: Heat shock protein 90 (Hsp90) protects cellular proteins from
      degradation by the ubiquitin-proteasome system in conditions of stress. Many
      cancers have increased expression of Hsp90 to ensure their malignant phenotype of
      increased proliferation, decreased apoptosis, and metastatic potential by
      conservation of proteins like epidermal growth factor receptor (EGFR), human
      epidermal growth factor receptor 2, anaplastic lymphoma kinase (ALK), v-Raf
      murine sarcoma viral oncogene homologue B1, AKT, B-cell lymphoma 2, and cell
      cycle proteins. This review discusses recent developments in the strategy of
      Hsp90 inhibition as a targeted therapy in non-small-cell lung cancer (NSCLC).
      RECENT FINDINGS: Hsp90 inhibitors result in growth inhibition and tumor
      regression in NSCLC cell lines and tumor xenograft models, both as monotherapy
      and in combination with other drugs. Hsp90 inhibition has particular efficacy in
      molecular subtypes of NSCLC, such as EGFR-mutated and ALK-rearranged NSCLC. IPI
      504 and ganetespib have activity in NSCLC both as monotherapy and in combination
      with docetaxel. SUMMARY: Preclinical studies and early clinical trials have
      confirmed the efficacy of Hsp90 inhibition as a targeted therapy in NSCLC.
      Ongoing trials will further define the utility of Hsp90 inhibitors in NSCLC.

PMID- 24463351
TI  - Pilot Experimental Study on the Effect of Arginine, Glutamine, and beta-Hydroxy
      beta-Methylbutyrate on Secondary Wound Healing.
AB  - BACKGROUND: Wound healing is a complex process, dependent on available nutrition
      substrates. When used together with beta-hydroxy beta-methylbutyrate, arginine
      and glutamine have been shown to increase collagen deposition in human subjects.
      However, there are no experimental investigations on the influence of this amino
      acid mixture with regard to secondary wound healing. The aim of this study is to
      investigate the effects of the supplementation of these 3 amino acids on the
      healing of open wounds in otherwise healthy animals. MATERIALS AND METHODS:
      Twelve rats were divided into control and treatment groups. Two 2-cm * 1-cm full
      thickness skin defects were prepared on each subject. The rats in both groups
      received a diet containing 1.2 g of protein per 100 g of body weight per day. The
      treatment group, in addition, received 200 mg/kg L-arginine, 200 mg/kg L
      glutamine, and 40 mg/kg beta-hydroxy beta-methylbutyrate every day. Wound sizes
      were measured every 2 days. On the 10th day, tissue samples were taken for
      histopathologic evaluation and also for the measurement of hydroxyproline
      concentrations. RESULTS: There was no statistically significant difference
      between mean wound sizes for the 2 groups (P > .05). There was also no
      statistically significant difference between the groups with regard to
      histological healing parameters (reepithelialization [P = 1.00], granulation
      tissue [P = 1.00], collagen accumulation [P = .455], inflammatory cell
      accumulation [P = .455], angiogenesis [P = .242]) or tissue hydroxyproline
      concentrations (P = .240). CONCLUSION: Diet supplemented with arginine,
      glutamine, and beta-hydroxy beta-methylbutyrate is not beneficial in enhancing
      secondary healing of open wounds in rats. Further research regarding this topic
      is warranted.

PMID- 24463352
TI  - Pharmacologic management of diarrhea in patients with short bowel syndrome.
AB  - Diarrhea associated with short bowel syndrome (SBS) can have multiple etiologies,
      including accelerated intestinal transit, gastric acid hypersecretion, intestinal
      bacterial overgrowth, and malabsorption of fats and bile salts. As a result,
      patients may need multiple medications to effectively control fecal output. The
      armamentarium of antidiarrheal drugs includes antimotility agents, antisecretory
      drugs, antibiotics and probiotics, bile acid-binding resins, and pancreatic
      enzymes. An antidiarrheal regimen must be individualized for each patient and
      should be developed using a methodical, stepwise approach. Treatment should be
      initiated with a single first-line medication at the low end of its dosing range.
      Dosage and/or dosing frequency can then be slowly escalated to achieve maximal
      effect while minimizing adverse events. If diarrhea remains poorly controlled,
      additional agents can be incorporated sequentially. If modification of the
      regimen is required, a single medication should be altered or exchanged at a
      time. After each adjustment of the regimen, sufficient time should be permitted
      to fully assess response (>=3-5 days) before initiating additional changes. SBS
      associated malabsorption is a major obstacle to optimization of an antidiarrheal
      regimen because drug absorption is impaired. Patients may benefit from high
      dosages and/or frequent dosing intervals, liquid preparations, or nonoral routes
      of drug delivery. Although the diarrhea associated with SBS can be debilitating,
      effective pharmaceutical management has the potential to substantially improve
      health outcomes and quality of life for these patients. 

PMID- 24463353
TI  - Cost of detecting a chronic solvent encephalopathy case by screening.
AB  - BACKGROUND: Stepwise screening of chronic solvent encephalopathy (CSE), using a
      postal survey followed by clinical examinations, has been shown to detect
      symptomatic exposed workers with an occupational disease even in industrialized
      countries with long-term, but relatively low dose exposure. Previous studies have
      suggested under-detection and late recognition of CSE, when work ability is
      already markedly reduced. AIMS: The aim was to estimate the cost of detecting one
      new CSE case by screening and diagnostics, to estimate the career extension
      needed to cover the cost of screening, and to study the work ability of the CSE
      cases. METHODS: A financial analysis of stepwise postal CSE screening followed by
      clinical examinations (SPC screening) was carried out, and the results were
      compared to those of the group of CSE cases referred to the Finnish Institute of
      Occupational Health (FIOH) by the existing national practice of occupational
      health services (OHS screening). The work ability of the SPC screened CSE cases
      was studied in relation to the retirement rate and the Work Ability Index (WAI).
      RESULTS: An analysis of the costs of detecting a new verified CSE case revealed
      them to be approximately 16,500 USD. Using the mean monthly wages in the fields
      concerned, we showed that if a worker is able to continue working for four months
      longer, the screening covers these costs. The cost for detecting a CSE case was
      twenty times higher with the existing OHS routine, when actualized according to
      the national guidelines. A CSE case detected at an early stage enables
      occupational rehabilitation or measures to decrease solvent exposure. The
      retirement rate of the SPC screened CSE cases was significantly lower than that
      of the OHS screened cases (6.7% vs. 74%). The results suggest that SPC screening
      detects patients at an earlier stage of the disease, when they are still capable
      of working. Their WAI sores were nevertheless lower than those of the general
      population, implying a greater risk of becoming excluded from the labor market.
      CONCLUSION: Stepwise screening of CSE using a postal survey followed by clinical
      examinations detected new CSE cases at lower costs than existing OHS screening
      routines. Detecting CSE at an early stage prevents early retirement.

PMID- 24463354
TI  - Survival effect of first- and second-line treatments for patients with primary
      glioblastoma: a cohort study from a prospective registry, 1997-2010.
AB  - BACKGROUND: Prospective follow-up studies of large cohorts of patients with
      glioblastoma (GBM) are needed to assess the effectiveness of conventional
      treatments in clinical practice. We report GBM survival data from the Brain
      Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in
      Milan, Italy, which collected longitudinal data for all consecutive patients with
      GBM from 1997 to 2010. METHODS: Survival data were obtained from 764 patients
      (aged>16 years) with histologically confirmed primary GBM who were diagnosed and
      treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort
      II). Equivalent data from 490 GBM patients diagnosed and treated over the
      preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were
      available for comparison. Progression-free survival (PFS) was available from 361
      and 219 patients actively followed up at INCB in cohorts II and I, respectively.
      RESULTS: Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3
      years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively,
      in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival
      and PFS in cohort II was significantly associated with introduction of the Stupp
      protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for
      survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a
      27% relative decrease in the risk of recurrence. After recurrence, reoperation
      was performed in one-fifth of cohort I and in one-third of cohort II but was not
      effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy,
      mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone,
      fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in
      cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in
      cohort II). CONCLUSIONS: We found a significant increase in overall survival,
      PFS, and survival after recurrence after 2004, likely due to improvements in
      surgical techniques, introduction of the Stupp protocol as a first-line
      treatment, and new standard protocols for second-line chemotherapy and
      radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor
      recurrence did not improve survival.

PMID- 24463355
TI  - Silencing of protein kinase D2 induces glioma cell senescence via p53-dependent
      and -independent pathways.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive tumor of the
      central nervous system with a dismal prognosis for affected patients. Aberrant
      protein kinase C (PKC) signaling has been implicated in gliomagenesis, and a
      member of the PKC-activated protein kinase D (PRKD) family, PRKD2, was identified
      as mediator of GBM growth in vitro and in vivo. METHODS: The outcome of PRKD2
      silencing and pharmacological inhibition on glioma cell proliferation was
      established with different glioma cell lines. Western blotting, senescence
      assays, co-immunoprecipitation, fluorescence activated cell sorting, quantitative
      PCR, and immunofluorescence microscopy were utilized to analyze downstream
      signaling. RESULTS: RNA-interference (21-mer siRNA) and pharmacological
      inhibition (CRT0066101) of PRKD2 profoundly inhibited proliferation of p53(wt)
      (U87MG, A172, and primary GBM2), and p53(mut) (GM133, T98G, U251, and primary
      Gli25) glioma cells. In a xenograft experiment, PRKD2 silencing significantly
      delayed tumor growth of U87MG cells. PRKD2 silencing in p53(wt) and p53(mut)
      cells was associated with typical hallmarks of senescence and cell cycle arrest
      in G1. Attenuated AKT/PKB phosphorylation in response to PRKD2 silencing was a
      common observation made in p53(wt) and p53(mut) GBM cells. PRKD2 knockdown in
      p53(wt) cells induced upregulation of p53, p21, and p27 expression, decreased
      phosphorylation of CDK2 and/or CDK4, hypophosphorylation of retinoblastoma
      protein (pRb), and reduced transcription of E2F1. In p53(mut) GM133 and primary
      Gli25 cells, PRKD2 silencing increased p27 and p15 and reduced E2F1 transcription
      but did not affect pRb phosphorylation. CONCLUSIONS: PRKD2 silencing induces
      glioma cell senescence via p53-dependent and -independent pathways.

PMID- 24463356
TI  - Initial care and outcome of glioblastoma multiforme patients in 2 diverse health
      care scenarios in Brazil: does public versus private health care matter?.
AB  - BACKGROUND: The aim of this study was to describe the epidemiological and
      survival features of patients with glioblastoma multiforme treated in 2 health
      care scenarios--public and private--in Brazil. METHODS: We retrospectively
      analyzed clinical, treatment, and outcome characteristics of glioblastoma
      multiforme patients from 2003 to 2011 at 2 institutions. RESULTS: The median age
      of the 171 patients (117 public and 54 private) was 59.3 years (range, 18-84).
      The median survival for patients treated in private institutions was 17.4 months
      (95% confidence interval, 11.1-23.7) compared with 7.1 months (95% confidence
      interval, 3.8-10.4) for patients treated in public institutions (P < .001). The
      time from the first symptom to surgery was longer in the public setting (median
      of 64 days for the public hospital and 31 days for the private institution; P =
      .003). The patients at the private hospital received radiotherapy concurrent with
      chemotherapy in 59.3% of cases; at the public hospital, only 21.4% (P < .001).
      Despite these differences, the institution of treatment was not found to be an
      independent predictor of outcome (hazard ratio, 1.675; 95% confidence interval,
      0.951-2.949; P = .074). The Karnofsky performance status and any additional
      treatment after surgery were predictors of survival. A hazard ratio of 0.010 (95%
      confidence interval, 0.003-0.033; P < .001) was observed for gross total tumor
      resection followed by radiotherapy concurrent with chemotherapy. CONCLUSIONS:
      Despite obvious disparities between the hospitals, the medical assistance
      scenario was not an independent predictor of survival. However, survival was
      directly influenced by additional treatment after surgery. Therefore, increasing
      access to resources in developing countries like Brazil is critical.

PMID- 24463357
TI  - MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of
      IkappaBalpha both in vitro and in vivo.
AB  - BACKGROUND: Recent studies have revealed that miR-196a is upregulated in
      glioblastoma multiforme (GBM) and that it correlates with the clinical outcome of
      patients with GBM. However, its potential regulatory mechanisms in GBM have never
      been reported. METHODS: We used quantitative real-time PCR to assess miR-196a
      expression levels in 132 GBM specimens in a single institution. Oncogenic
      capability of miR-196a was detected by apoptosis and proliferation assays in
      U87MG and T98G cells. Immunohistochemistry was used to determine the expression
      of IkappaBalpha in GBM tissues, and a luciferase reporter assay was carried out
      to confirm whether IkappaBalpha is a direct target of miR-196a. In vivo,
      xenograft tumors were examined for an antiglioma effect of miR-196a inhibitors.
      RESULTS: We present for the first time evidence that miR-196a could directly
      interact with IkappaBalpha 3'-UTR to suppress IkappaBalpha expression and
      subsequently promote activation of NF-kappaB, consequently promoting
      proliferation of and suppressing apoptosis in GBM cells both in vitro and in
      vivo. Our study confirmed that miR-196a was upregulated in GBM specimens and that
      high levels of miR-196a were significantly correlated with poor outcome in a
      large cohort of GBM patients. Our data from human tumor xenografts in nude mice
      treated with miR-196 inhibitors demonstrated that inhibition of miR-196a could
      ameliorate tumor growth in vivo. CONCLUSIONS: MiR-196a exerts its oncogenic
      effect in GBM by inhibiting IkappaBalpha both in vitro and in vivo. Our findings
      provide new insights into the pathogenesis of GBM and indicate that miR-196a may
      predict clinical outcome of GBM patients and serve as a new therapeutic target
      for GBM.

PMID- 24463358
TI  - Abamectin is metabolized by CYP392A16, a cytochrome P450 associated with high
      levels of acaricide resistance in Tetranychus urticae.
AB  - Abamectin is one of the most important insecticides worldwide. It is used against
      major agricultural pests and insects of public health importance, as well as
      against endoparasites in animal health. Abamectin has been used successfully for
      the control of the spider mite Tetranychus urticae, a major agricultural pest
      with global distribution, an extremely diverse host range, and a remarkable
      ability to develop resistance against insecticides including abamectin. Target
      site resistance mutations may explain a large part of resistance, although
      genetic evidence and transcriptomic data indicated that additional mechanisms may
      also be implicated in the abamectin resistant phenotype. To investigate a
      functional link between cytochrome P450-mediated metabolism and abamectin
      resistance, we recombinantly expressed three cytochrome P450s (CYP392A16,
      CYP392D8 and CYP392D10) that have been associated with high levels of abamectin
      resistance in a resistant T. urticae strain isolated from Greece. CYP392A16 was
      expressed predominately in its P450 form however, both CYP392D8 and CYP392D10
      were expressed predominately as P420, despite optimization efforts on expression
      conditions. CYP392A16 catalyses the hydroxylation of abamectin (Kcat=0.54
      pmol/min/pmol P450; Km=45.9 MUM), resulting in a substantially less toxic
      compound as confirmed by bioassays with the partially purified metabolite.
      However, CYP392A16 did not metabolize hexythiazox, clofentezine and bifenthrin,
      active ingredients that also showed reduced toxicity in the abamectin resistant
      strain. Among a number of fluorescent and luminescent substrates screened,
      Luciferin-ME EGE was preferentially metabolized by CYP392A16, and it may be a
      potential diagnostic probe for metabolic resistance detection and monitoring.

PMID- 24463359
TI  - Identification of two acetylcholinesterases in Pardosa pseudoannulata and the
      sensitivity to insecticides.
AB  - Pardosa pseudoannulata is an important predatory enemy against insect pests, such
      as rice planthoppers and leafhoppers. In order to understand the insecticide
      selectivity between P. pseudoannulata and insect pests, two acetylcholinesterase
      genes, Pp-ace1 and Pp-ace2, were cloned from this natural enemy. The putative
      proteins encoded by Pp-ace1 and Pp-ace2 showed high similarities to insect AChE1
      (63% to Liposcelis entomophila AChE1) and AChE2 (36% to Culex quinquefasciatus
      AChE2) with specific functional motifs, which indicated that two genes might
      encode AChE1 and AChE2 proteins respectively. The recombinant proteins by
      expressing Pp-ace1 and Pp-ace2 genes in insect sf9 cells showed high AChE
      activities. The kinetic parameters, Vmax and Km, of two recombinant AChE proteins
      were significantly different. The sensitivities to six insecticides were
      determined in two recombinant AChEs. Pp-AChE1 was more sensitive to all tested
      insecticides than Pp-AChE2, such as fenobucarb (54 times in Ki ratios),
      isoprocarb (31 times), carbaryl (13 times) and omethoate (6 times). These results
      indicated that Pp-AChE1 might be the major synaptic enzyme in the spider. By
      sequence comparison of P. pseudoannulata and insect AChEs, the key amino acid
      differences at or close to the functional sites were found. The locations of some
      key amino acid differences were consistent with the point mutation sites in
      insect AChEs that were associated with insecticide resistance, such as Phe331 in
      Pp-AChE2 corresponding to Ser331Phe mutation in Myzus persicae and Aphis gossypii
      AChE2, which might play important roles in insecticide selectivity between P.
      pseudoannulata and insect pests. Of course, the direct evidences are needed
      through further studies. 

PMID- 24463360
TI  - Nanoparticle assembly: building blocks for tumour delivery.

PMID- 24463361
TI  - DNA assembly of nanoparticle superstructures for controlled biological delivery
      and elimination.
AB  - The assembly of nanomaterials using DNA can produce complex nanostructures, but
      the biological applications of these structures remain unexplored. Here, we
      describe the use of DNA to control the biological delivery and elimination of
      inorganic nanoparticles by organizing them into colloidal superstructures. The
      individual nanoparticles serve as building blocks, whose size, surface chemistry
      and assembly architecture dictate the overall superstructure design. These
      superstructures interact with cells and tissues as a function of their design,
      but subsequently degrade into building blocks that can escape biological
      sequestration. We demonstrate that this strategy reduces nanoparticle retention
      by macrophages and improves their in vivo tumour accumulation and whole-body
      elimination. Superstructures can be further functionalized to carry and protect
      imaging or therapeutic agents against enzymatic degradation. These results
      suggest a different strategy to engineer nanostructure interactions with
      biological systems and highlight new directions in the design of biodegradable
      and multifunctional nanomedicine. 

PMID- 24463362
TI  - Bacillus spores as building blocks for stimuli-responsive materials and
      nanogenerators.
AB  - Materials that respond mechanically to external chemical stimuli have
      applications in biomedical devices, adaptive architectural systems, robotics and
      energy harvesting. Inspired by biological systems, stimuli-responsive materials
      have been created that can oscillate, transport fluid, provide homeostasis and
      undergo complex changes in shape. However, the effectiveness of synthetic stimuli
      responsive materials in generating work is limited when compared with mechanical
      actuators. Here, we show that the mechanical response of Bacillus spores to water
      gradients exhibits an energy density of more than 10 MJ m(-3), which is two
      orders of magnitude higher than synthetic water-responsive materials. We also
      identified mutations that can approximately double the energy density of the
      spores and found that they can self-assemble into dense, submicrometre-thick
      monolayers on substrates such as silicon microcantilevers and elastomer sheets,
      creating bio-hybrid hygromorph actuators. To illustrate the potential
      applications of the spores, we used them to build an energy-harvesting device
      that can remotely generate electrical power from an evaporating body of water.

PMID- 24463364
TI  - Impact of local compressive stress on the optical transitions of single organic
      dye molecules.
AB  - The ability to mechanically control the optical properties of individual
      molecules is a grand challenge in nanoscience and could enable the manipulation
      of chemical reactivity at the single-molecule level. In the past, light has been
      used to alter the emission wavelength of individual molecules or modulate the
      energy transfer quantum yield between them. Furthermore, tensile stress has been
      applied to study the force dependence of protein folding/unfolding and of the
      chemistry and photochemistry of single molecules, although in these mechanical
      experiments the strength of the weakest bond limits the amount of applicable
      force. Here, we show that compressive stress modifies the photophysical
      properties of individual dye molecules. We use an atomic force microscope tip to
      prod individual molecules adsorbed on a surface and follow the effect of the
      applied force on the electronic states of the molecule by fluorescence
      spectroscopy. Applying a localized compressive force on an isolated molecule
      induces a stress that is redistributed throughout the structure. Accordingly, we
      observe reversible spectral shifts and even shifts that persist after retracting
      the microscope tip, which we attribute to transitions to metastable states. Using
      quantum-mechanical calculations, we show that these photophysical changes can be
      associated with transitions among the different possible conformers of the
      adsorbed molecule. 

PMID- 24463363
TI  - Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in
      living mice.
AB  - Photoacoustic imaging holds great promise for the visualization of physiology and
      pathology at the molecular level with deep tissue penetration and fine spatial
      resolution. To fully utilize this potential, photoacoustic molecular imaging
      probes have to be developed. Here, we introduce near-infrared light absorbing
      semiconducting polymer nanoparticles as a new class of contrast agents for
      photoacoustic molecular imaging. These nanoparticles can produce a stronger
      signal than the commonly used single-walled carbon nanotubes and gold nanorods on
      a per mass basis, permitting whole-body lymph-node photoacoustic mapping in
      living mice at a low systemic injection mass. Furthermore, the semiconducting
      polymer nanoparticles possess high structural flexibility, narrow photoacoustic
      spectral profiles and strong resistance to photodegradation and oxidation,
      enabling the development of the first near-infrared ratiometric photoacoustic
      probe for in vivo real-time imaging of reactive oxygen species--vital chemical
      mediators of many diseases. These results demonstrate semiconducting polymer
      nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular
      probes.

PMID- 24463365
TI  - Systematic screen for mutants resistant to TORC1 inhibition in fission yeast
      reveals genes involved in cellular ageing and growth.
AB  - Target of rapamycin complex 1 (TORC1), which controls growth in response to
      nutrients, promotes ageing in multiple organisms. The fission yeast
      Schizosaccharomyces pombe emerges as a valuable genetic model system to study
      TORC1 function and cellular ageing. Here we exploited the combinatorial action of
      rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent
      manner. We screened a deletion library, comprising ~84% of all non-essential
      fission yeast genes, for drug-resistant mutants. This screen identified 33 genes
      encoding functions such as transcription, kinases, mitochondrial respiration,
      biosynthesis, intra-cellular trafficking, and stress response. Among the
      corresponding mutants, 5 showed shortened and 21 showed increased maximal
      chronological lifespans; 15 of the latter mutants showed no further lifespan
      increase with rapamycin and might thus represent key targets downstream of TORC1.
      We pursued the long-lived sck2 mutant with additional functional analyses,
      revealing that the Sck2p kinase functions within the TORC1 network and is
      required for normal cell growth, global protein translation, and ribosomal S6
      protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth
      was associated with all long-lived mutants while oxidative-stress resistance was
      not. 

PMID- 24463366
TI  - Feminization of pheromone-sensing neurons affects mating decisions in Drosophila
      males.
AB  - The response of individual animals to mating signals depends on the sexual
      identity of the individual and the genetics of the mating targets, which
      represent the mating social context (social environment). However, how social
      signals are sensed and integrated during mating decisions remains a mystery. One
      of the models for understanding mating behaviors in molecular and cellular terms
      is the male courtship ritual in the fruit fly (Drosophila melanogaster). We have
      recently shown that a subset of gustatory receptor neurons (GRNs) that are
      enriched in the male appendages and express the ion channel ppk23 play a major
      role in the initiation and maintenance of male courtship via the perception of
      cuticular contact pheromones, and are likely to represent the main chemosensory
      pathway that influences mating decisions by males. Here we show that genetic
      feminization of ppk23-expressing GRNs in male flies resulted in a significant
      increase in male-male sexual attraction without an apparent impact on sexual
      attraction to females. Furthermore, we show that this increase in male-male
      sexual attraction is sensory specific, which can be modulated by variable social
      contexts. Finally, we show that feminization of ppk23-expressing sensory neurons
      lead to major transcriptional shifts, which may explain the altered
      interpretation of the social environment by feminized males. Together, these data
      indicate that the sexual cellular identity of pheromone sensing GRNs plays a
      major role in how individual flies interpret their social environment in the
      context of mating decisions. 

PMID- 24463367
TI  - Topoisomerase IIbeta is required for proper retinal development and survival of
      postmitotic cells.
AB  - Topoisomerase IIbeta (Top2b) is an enzyme that modulates DNA supercoiling by
      catalyzing the passage of DNA duplexes through one another. It is ubiquitously
      expressed in postmitotic cells and known to function during the development of
      neuromuscular junctions in the diaphragm and the proper formation of laminar
      structure in the cerebral cortex. However, due to the perinatal death phenotype
      of the traditional constitutive and brain-specific Top2b knockout mice, the
      precise in vivo function of Top2b, especially during postnatal neural
      development, remains to be determined. Using both the constitutive and retina
      specific knockout mouse models, we showed that Top2b deficiency resulted in
      delayed neuronal differentiation, degeneration of the plexiform layers and outer
      segment of photoreceptors, as well as dramatic reduction in cell number in the
      retina. Genome-wide transcriptome analysis by RNA sequencing revealed that genes
      involved in neuronal survival and neural system development were preferentially
      affected in Top2b-deficient retinas. Collectively, our findings have indicated an
      important function of Top2b in proper development and the maintenance/survival of
      postmitotic neurons in the retina. 

PMID- 24463368
TI  - Double-stranded RNA-dependent protein kinase deficiency protects the heart from
      systolic overload-induced congestive heart failure.
AB  - BACKGROUND: Double-stranded RNA-dependent protein kinase (PKR) is a eukaryotic
      initiation factor 2alpha kinase that inhibits mRNA translation under stress
      conditions. PKR also mediates inflammatory and apoptotic signaling independently
      of translational regulation. Congestive heart failure is associated with
      cardiomyocyte hypertrophy, inflammation, and apoptosis, but the role of PKR in
      left ventricular hypertrophy and the development of congestive heart failure has
      not been examined. METHODS AND RESULTS: We observed increased myocardial PKR
      expression and translocation of PKR into the nucleus in humans and mice with
      congestive heart failure. To determine the impact of PKR on the development of
      congestive heart failure, PKR knockout and wild-type mice were exposed to
      pressure overload produced by transverse aortic constriction. Although heart size
      increased similarly in wild-type and PKR knockout mice after transverse aortic
      constriction, PKR knockout mice exhibited very little pulmonary congestion, well
      preserved left ventricular ejection fraction and contractility, and significantly
      less myocardial fibrosis compared with wild-type mice. Bone marrow-derived cells
      from wild-type mice did not abolish the cardiac protective effect observed in PKR
      knockout mice, whereas bone marrow-derived cells from PKR knockout mice had no
      cardiac protective effect in wild-type mice. Mechanistically, PKR knockout
      attenuated transverse aortic constriction-induced tumor necrosis factor-alpha
      expression and leukocyte infiltration and lowered cardiac expression of
      proapoptotic factors (Bax and caspase-3), so that PKR knockout hearts were more
      resistant to transverse aortic constriction-induced cardiomyocyte apoptosis. PKR
      depletion in isolated cardiomyocytes also conferred protection against tumor
      necrosis factor-alpha- or lipopolysaccharide-induced apoptosis. CONCLUSION: PKR
      is a maladaptive factor upregulated in hemodynamic overload that contributes to
      myocardial inflammation, cardiomyocyte apoptosis, and the development of
      congestive heart failure.

PMID- 24463369
TI  - Dominant frequency increase rate predicts transition from paroxysmal to long-term
      persistent atrial fibrillation.
AB  - BACKGROUND: Little is known about the mechanisms underlying the transition from
      paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long
      standing persistent AF we tested the hypothesis that the rate of electric and
      structural remodeling, assessed by dominant frequency (DF) changes, determines
      the time at which AF becomes persistent. METHODS AND RESULTS: Self-sustained AF
      was induced by atrial tachypacing. Seven sheep were euthanized 11.5+/-2.3 days
      after the transition to persistent AF and without reversal to sinus rhythm; 7
      sheep were euthanized after 341.3+/-16.7 days of long-standing persistent AF.
      Seven sham-operated animals were in sinus rhythm for 1 year. DF was monitored
      continuously in each group. Real-time polymerase chain reaction, Western
      blotting, patch clamping, and histological analyses were used to determine the
      changes in functional ion channel expression and structural remodeling. Atrial
      dilatation, mitral valve regurgitation, myocyte hypertrophy, and atrial fibrosis
      occurred progressively and became statistically significant after the transition
      to persistent AF, with no evidence for left ventricular dysfunction. DF increased
      progressively during the paroxysmal-to-persistent AF transition and stabilized
      when AF became persistent. Importantly, the rate of DF increase correlated
      strongly with the time to persistent AF. Significant action potential duration
      abbreviation, secondary to functional ion channel protein expression changes
      (CaV1.2, NaV1.5, and KV4.2 decrease; Kir2.3 increase), was already present at the
      transition and persisted for 1 year of follow up. CONCLUSIONS: In the sheep model
      of long-standing persistent AF, the rate of DF increase predicts the time at
      which AF stabilizes and becomes persistent, reflecting changes in action
      potential duration and densities of sodium, L-type calcium, and inward rectifier
      currents.

PMID- 24463371
TI  - Assessing the accuracy of physical models used in protein-folding simulations:
      quantitative evidence from long molecular dynamics simulations.
AB  - Advances in computer hardware, software and algorithms have now made it possible
      to run atomistically detailed, physics-based molecular dynamics simulations of
      sufficient length to observe multiple instances of protein folding and unfolding
      within a single equilibrium trajectory. Although such studies have already begun
      to provide new insights into the process of protein folding, realizing the full
      potential of this approach will depend not only on simulation speed, but on the
      accuracy of the physical models ('force fields') on which such simulations are
      based. While experimental data are not available for comparison with all of the
      salient characteristics observable in long protein-folding simulations, we
      examine here the extent to which current force fields reproduce (and fail to
      reproduce) certain relevant properties for which such comparisons are possible. 

PMID- 24463373
TI  - [Cardiac arrhythmias].

PMID- 24463370
TI  - Variations in cause and management of atrial fibrillation in a prospective
      registry of 15,400 emergency department patients in 46 countries: the RE-LY
      Atrial Fibrillation Registry.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia;
      however, little is known about patients in a primary care setting from high-,
      middle-, and low-income countries. METHODS AND RESULTS: This prospective registry
      enrolled patients presenting to an emergency department with AF at 164 sites in
      46 countries representing all inhabited continents. Patient characteristics were
      compared among 9 major geographic regions. Between September 2008 and April 2011,
      15,400 patients were enrolled. The average age was 65.9, standard deviation 14.8
      years, ranging from 57.2, standard deviation 18.8 years in Africa, to 70.1,
      standard deviation 13.4 years in North America, P<0.001. Hypertension was
      globally the most common risk factor for AF, ranging in prevalence from 41.6% in
      India to 80.7% in Eastern Europe, P<0.001. Rheumatic heart disease was present in
      only 2.2% of North American patients, in comparison with 21.5% in Africa and
      31.5% in India, P<0.001. The use of oral anticoagulation among patients with a
      CHADS2 score of >=2 was greatest in North America (65.7%) but was only 11.2% in
      China, P<0.001. The mean time in the therapeutic range was 62.4% in Western
      Europe, 50.9% in North America, but only between 32% and 40% in India, China,
      Southeast Asia, and Africa, P<0.001. CONCLUSIONS: There is a large global
      variation in age, risk factors, concomitant diseases, and treatment of AF among
      regions. Improving outcomes globally requires an understanding of this variation
      and the conduct of research focused on AF associated with different underlying
      conditions and treatment of AF and predisposing conditions in different
      socioeconomic settings.

PMID- 24463372
TI  - Slowing down single-molecule trafficking through a protein nanopore reveals
      intermediates for peptide translocation.
AB  - The microscopic details of how peptides translocate one at a time through
      nanopores are crucial determinants for transport through membrane pores and
      important in developing nano-technologies. To date, the translocation process has
      been too fast relative to the resolution of the single molecule techniques that
      sought to detect its milestones. Using pH-tuned single-molecule electrophysiology
      and molecular dynamics simulations, we demonstrate how peptide passage through
      the alpha-hemolysin protein can be sufficiently slowed down to observe
      intermediate single-peptide sub-states associated to distinct structural
      milestones along the pore, and how to control residence time, direction and the
      sequence of spatio-temporal state-to-state dynamics of a single peptide.
      Molecular dynamics simulations of peptide translocation reveal the time-
      dependent ordering of intermediate structures of the translocating peptide inside
      the pore at atomic resolution. Calculations of the expected current ratios of the
      different pore-blocking microstates and their time sequencing are in accord with
      the recorded current traces. 

PMID- 24463374
TI  - [Syncope-- reasonable diagnostic tools to identify potentially dangerous
      syncopes].
AB  - Syncopes are quite often seen by family doctors and in emergency wards. It is of
      utmost importance to differentiate between syncope of cardiac and non-cardiac
      origin, as prognosis and work-up are very different. Regularly used diagnostic
      tools, their indication and yield and finally an algorithm for a work-up are
      outlined. 

PMID- 24463375
TI  - [Rational use of ambulatory ECG recordings].
AB  - Ambulatory ECG recordings and the memory function of cardiac devices are very
      useful to record arrhythmias. For this purpose various modalities of
      documentation are available including externally worn ECGs with variable
      recording duration and implantable cardiac devices with recording periods over
      years. The probably most frequent indication for an ambulatory ECG recording is
      syncope. In contrast to episodic palpitations, syncope is associated with
      hemodynamic impairment and reduced cerebral perfusion which precludes visiting a
      physician in order to record an ECG during the attack. Furthermore, ambulatory
      ECG might be useful in patients with short-lasting palpitations. A selective
      application of this diagnostic tool might also be appropriate in asymptomatic
      patients, particularly in order to search for episodes of atrial fibrillation.
      This indication is of great interest since the introduction of pulmonary vein
      isolation as a valuable therapeutic option in atrial fibrillation patients to
      document asymptomatic recurrences for quality control reasons. 

PMID- 24463376
TI  - [Atrial fibrillation-pharmacological therapy for rate and rhythm control].
AB  - The therapeutic management of patients with atrial fibrillation is based on the
      three pillars (1) prevention of thromboembolism, (2) rate control, and (3) rhythm
      control. Patients with one or more risk factors should be treated with an oral
      anticoagulants in order to prevent stroke and to reduce mortality. The goals of
      rate control, prevention of heart failure and alleviation of atrial fibrillation
      related symptoms, normally can be achieved by pharmacological agents slowing the
      conduction in the AV node (e. g. beta-blockers, calcium channel blockers,
      digoxin). For patients remaining symptomatic despite sufficient rate control
      adding a rhythm control strategy may be considered. The currently available
      antiarrhythmic drugs (e. g. flecainide, propafenone, sotalol, dronedarone,
      amiodarone) are characterized by a rather low efficacy in maintaining sinus
      rhythm and various possibly life threatening side effects. Therefore, invasive
      therapies as catheter ablation are frequently needed to achieve rhythm control in
      symptomatic patients with atrial fibrillation. 

PMID- 24463377
TI  - [Interventional treatment of atrial fibrillation - indication, techniques and
      success rates].
AB  - Atrial fibrillation is the most common cardiac arrhythmia occurring in 2 % of the
      population. Aside from initiating oral anticoagulation in patients with an
      increased risk for thromboembolic complications, rhythm control often is the
      therapeutic target, particularly in the young and highly symptomatic. The
      ablation of patients with paroxysmal atrial fibrillation has emerged as an
      alternative to long-term treatment with antiarrhythmic drugs. It targets to
      isolate the pulmonary veins as the main triggers for atrial fibrillation in
      structurally normal atria. In the case of long-standing persistent atrial
      fibrillation, there is no agreement about the ablation strategy and the success
      rates are significantly lower. This review addresses the underlying
      pathophysiology, the ablation techniques, success rates and complications as well
      as alternative invasive treatment options. 

PMID- 24463378
TI  - [Contemporary treatment of atrial flutter].
AB  - Atrial flutter is a relatively common arrhythmia that may be associated with
      substantial symptoms and morbidity. It can be harmful by impairing the cardiac
      output and by encouraging atrial thrombus formation that can lead to systemic
      embolization. In patients with atrial flutter four major issues that must be
      addressed. These are reversion to normal sinus rhythm, maintenance of sinus
      rhythm, control of the ventricular rate, and prevention of systemic thrombo
      embolism. Nowadays, catheter ablation is the first line treatment of recurrent
      symptomatic or hemodynamically significant atrial flutter. 

PMID- 24463379
TI  - [Paroxysmal supraventricular tachycardia-mechanisms, diagnostic, and treatment].
AB  - Paroxysmal supraventricular tachycardia have their origin above the His bundle.
      However, this definition has a historical origin and is imprecise regarding AV
      reentry tachycardia using an accessory pathways since this tachycardia use the
      ventricule a part of the reentry-circuit. The most common supraventricular
      tachycardia is the atrioventricular nodal re-entry tachycardia, which is caused
      by a re-entrant tachycardia that involves the AV node and the atrial tissue
      followed by the atrioventricular re-entry tachycardia using an accessory pathway.
      More prevalent are sinus tachycardia, which is often physiologic and atrial
      fibrillation/flutter which are covered in detail by other articles within this
      issue of Therapeutischen Umschau. Therefore, the main topic of this review is the
      discussion of the mechanisms, diagnosis and treatment of AV nodal reentry
      tachycardia, AV reentry tachycardia using an accessory pathway and to a less
      extent focal atrial tachycardia. 

PMID- 24463380
TI  - [Treatment of bradycardias - who needs a pacemaker?].
AB  - Bradyarrhythmias are caused by a disturbed impulse formation in the sinus node
      and/or a disturbed impulse conduction and can be subclassified clinically as
      sinus node dysfunction, atrioventricular (AV) block, or functional bradycardia.
      Persistent bradycardia can be diagnosed by standard ECG. For diagnosis of
      intermittent bradycardia, often long-term ECG monitoring and/or additional
      testing is necessary. Symptomatic bradycardias are the standard indication for
      cardiac pacing after exclusion of reversible causes. Since sinus node dysfunction
      is associated with a good prognosis, pacing in this condition is only indicated
      in the presence of bradycardia-related symptoms. For prognostic reasons,
      pacemaker implantation is indicated in third degree AV block and second degree AV
      block Mobitz Type II, even if asymptomatic. Cardiac pacing for recurrent
      unpredictable neurocardiogenic syncope due to a cardioinhibitory reflex should be
      considered in certain circumstances. The implantation of cardiac pacemakers has
      been performed for more than half of a century. Due to the enormous technological
      progress, pacemaker implantations can nowadays be performed under local
      anesthesia in an outpatient setting. However, complications of pacemaker therapy
      are still not uncommon. 

PMID- 24463381
TI  - [Current indications for an implantable cardioverter defibrillator (ICD)].
AB  - Sudden cardiac death is one of the leading causes of death in industrialized
      countries. The implantable cardioverter/defibrillator (ICD) is the most effective
      treatment for malignant ventricular tachyarrhythmias. Current guidelines
      recommend the implantation of a defibrillator in patients who experienced
      ventricular tachycardia or fibrillation (secondary prevention of sudden cardiac
      death), as well as in high risk patients for primary prevention. The latter are
      patients with impaired left ventricular function <= 35 %. With the exception of
      secondary prevention indications (ie. after a "survived sudden cardiac death")
      indications for ICD implantation in the context of other cardiomyopathies, such
      as hypertrophic (obstructive) cardiomyopathy and arrhythmogenic right ventricular
      cardiomyopathy (ARVC), and of channelopathies, such as Brugada syndrome and long
      QT syndrome are complex. Before deciding to implant an ICD, the indication as
      well as the potential complications (inappropriate shocks, risk of infection,
      device or lead replacement, costs, etc.) have to be considered and discussed in
      detail with the patients and their relatives. There are very few specific hazards
      or significant limitations in daily life for the patient and his environment
      caused by the ICD. An ICD can be transiently deactivated if necessary by using a
      magnet (eg. during surgery) or permanently deactivated by re-programming the
      device (eg. palliative care). 

PMID- 24463382
TI  - An improved distance-driven method for projection and backprojection.
AB  - Fast and accurate image reconstruction is the ultimate goal of iterative methods
      for limited-angle, few-view, interior problems, etc. Recently, a finite-detector
      based projection model was proposed for iterative CT reconstructions, which was
      called area integral model (AIM) and has shown a high spatial resolution but with
      a high computational complexity. On the other hand, the distance-driven model
      (DDM) is the state-of-the-art technology to model forward projection and
      backprojection, which has shown a low computational complexity but relative low
      spatial resolution than AIM-based method. Inspired by the DDM, here we propose an
      improved distance-driven model (IDDM), which has a similar computational
      complexity with the DDM-based method and comparative spatial resolution with the
      AIM-based method. In an ordered-subset simultaneous algebraic reconstruction
      technique (OS-SART) framework, the AIM, IDDM and DDM are implemented and
      evaluated using a sinogram from a phantom experiment on a Discovery CT750 HD
      scanner. The results show that the computational cost of DDM- and IDDM-based
      methods is similar, which is 6 to 13~times faster than the AIM-based method
      assuming the same number of iterations. The spatial resolution of AIM- and IDDM
      based method is comparable, which is better than DDM-based method in terms of
      full-width-of-half-maximum (FWHM). 

PMID- 24463383
TI  - Practical geometric calibration for helical cone-beam industrial computed
      tomography.
AB  - In helical cone-beam industrial computed tomography (ICT), the reconstructed
      images may be interfered by geometry artifacts due to the presence of mechanical
      misalignments. To obtain artifact-free reconstruction images, a practical
      geometric calibration method for helical scan is investigated based on Noo's
      analytic geometric calibration method for circular scan. The presented method is
      implemented by first dividing the whole ascending path of helical scan into
      several pieces, then acquiring the projections of a dedicated calibration phantom
      in circular scan at each section point, of which geometry parameters are
      calculated using Noo's analytic method. At last, the geometry parameters of each
      projection in a piece can be calculated by those of the two end points of the
      piece. We performed numerical simulations and real data experiments to study the
      performance of the presented method. The experimental results indicated that the
      method can obtain high-precision geometry parameters of helical scan and give
      satisfactory reconstruction images. 

PMID- 24463384
TI  - Interior reconstruction method based on rotation-translation scanning model.
AB  - In various applications of computed tomography (CT), it is common that the
      reconstructed object is over the field of view (FOV) or we may intend to sue a
      FOV which only covers the region of interest (ROI) for the sake of reducing
      radiation dose. These kinds of imaging situations often lead to interior
      reconstruction problems which are difficult cases in the reconstruction field of
      CT, due to the truncated projection data at every view angle. In this paper, an
      interior reconstruction method is developed based on a rotation-translation (RT)
      scanning model. The method is implemented by first scanning the reconstructed
      region, and then scanning a small region outside the support of the reconstructed
      object after translating the rotation centre. The differentiated backprojection
      (DBP) images of the reconstruction region and the small region outside the object
      can be respectively obtained from the two-time scanning data without data
      rebinning process. At last, the projection onto convex sets (POCS) algorithm is
      applied to reconstruct the interior region. Numerical simulations are conducted
      to validate the proposed reconstruction method. 

PMID- 24463385
TI  - EDART, a discrete algebraic reconstructing technique for experimental data
      obtained with high resolution computed tomography.
AB  - A novel reconstruction method is presented to improve the image quality of three
      dimensional (3D) datasets for samples consisting of only one material and
      surrounding air, obtained with high resolution X-ray Computed Tomography (MUCT).
      It combines discrete tomography with iterative reconstruction algorithms, it is
      applicable for routine MUCT applications and is referred to as the Experimental
      Discrete Algebraic Reconstruction Technique (EDART). A fast and intuitive method
      to estimate the attenuation coefficient and segmentation threshold, in case these
      are unknown, is included. Experimental results illustrate that EDART allows the
      improvement of the reconstruction quality as compared to standard iterative
      reconstruction when few projections are available, without significantly
      increasing the reconstruction time. 

PMID- 24463386
TI  - X-ray strain tensor imaging: FEM simulation and experiments with a micro-CT.
AB  - In tissue elasticity imaging, measuring the strain tensor components is necessary
      to solve the inverse problem. However, it is impractical to measure all the
      tensor components in ultrasound or MRI elastography because of their anisotropic
      spatial resolution. The objective of this study is to compute 3D strain tensor
      maps from the 3D CT images of a tissue-mimicking phantom. We took 3D micro-CT
      images of the phantom twice with applying two different mechanical compressions
      to it. Applying the 3D image correlation technique to the CT images under
      different compression, we computed 3D displacement vectors and strain tensors at
      every pixel. To evaluate the accuracy of the strain tensor maps, we made a 3D FEM
      model of the phantom, and we computed strain tensor maps through FEM simulation.
      Experimentally obtained strain tensor maps showed similar patterns to the FEM
      simulated ones in visual inspection. The correlation between the strain tensor
      maps obtained from the experiment and the FEM simulation ranges from 0.03 to
      0.93. Even though the strain tensor maps suffer from high level noise, we expect
      the x-ray strain tensor imaging may find some biomedical applications such as
      malignant tissue characterization and stress analysis inside the tissues. 

PMID- 24463387
TI  - Adaptive zooming in X-ray computed tomography.
AB  - BACKGROUND: In computed tomography (CT), the source-detector system commonly
      rotates around the object in a circular trajectory. Such a trajectory does not
      allow to exploit a detector fully when scanning elongated objects. OBJECTIVE:
      Increase the spatial resolution of the reconstructed image by optimal zooming
      during scanning. METHODS: A new approach is proposed, in which the full width of
      the detector is exploited for every projection angle. This approach is based on
      the use of prior information about the object's convex hull to move the source as
      close as possible to the object, while avoiding truncation of the projections.
      RESULTS: Experiments show that the proposed approach can significantly improve
      reconstruction quality, producing reconstructions with smaller errors and
      revealing more details in the object. CONCLUSIONS: The proposed approach can lead
      to more accurate reconstructions and increased spatial resolution in the object
      compared to the conventional circular trajectory.

PMID- 24463388
TI  - Optimizing contrast agents with respect to reducing beam hardening in nonmedical
      X-ray computed tomography experiments.
AB  - Iodine is commonly used as a contrast agent in nonmedical science and
      engineering, for example, to visualize Darcy flow in porous geological media
      using X-ray computed tomography (CT). Undesirable beam hardening artifacts occur
      when a polychromatic X-ray source is used, which makes the quantitative analysis
      of CT images difficult. To optimize the chemistry of a contrast agent in terms of
      the beam hardening reduction, we performed computer simulations and generated
      synthetic CT images of a homogeneous cylindrical sand-pack (diameter, 28 or 56
      mm; porosity, 39 vol.% saturated with aqueous suspensions of heavy elements
      assuming the use of a polychromatic medical CT scanner. The degree of cupping
      derived from the beam hardening was assessed using the reconstructed CT images to
      find the chemistry of the suspension that induced the least cupping. The results
      showed that (i) the degree of cupping depended on the position of the K
      absorption edge of the heavy element relative to peak of the polychromatic
      incident X-ray spectrum, (ii) (53)I was not an ideal contrast agent because it
      causes marked cupping, and (iii) a single element much heavier than (53)I ((64)Gd
      to (79)Au) reduced the cupping artifact significantly, and a four-heavy-element
      mixture of elements from (64)Gd to (79)Au reduced the artifact most
      significantly.

PMID- 24463389
TI  - Coherent soft X-ray high-order harmonics using tight-focusing laser pulses in the
      gas mixture.
AB  - We experimentally study the harmonics from a Xe-He gas mixture using tight
      focusing femtosecond laser pulses. The spectrum in the mixed gases exhibits an
      extended cutoff region from the harmonic H21 to H27. The potential explanation is
      that the harmonics photons from Xe contribute the electrons of He atoms to
      transmit into the excited-state. Therefore, the harmonics are emitted from He
      atoms easily. Furthermore, we show that there are the suppressed harmonics H15
      and H17 in the mixed gases. The underlying mechanism is the destructive
      interference between harmonics generated from different atoms. Our results
      indicate that HHG from Xe-He gas mixture is an efficient method of obtaining the
      coherent soft X-ray source. 

PMID- 24463390
TI  - The effect of detector size and energy resolution on image quality in multi
      projection Compton scatter tomography.
AB  - The reconstructed electron density image quality is sensitive to the detector
      size and energy resolution, which contribute to the blurring and noise in the
      image. This work evaluates optimal values of the detector parameters for a
      realistic system through analytical simulations of the transverse slice of the
      dedicated breast CT system geometry. This study introduces a spectroscopic x-ray
      tomography technique which uses multiple projections to reconstruct electron
      density images by backprojecting scattered photons over isogonic curves. The
      reconstruction can be obtained using a single projection yet its quality degrades
      as the acquisition conditions i.e. detector size and energy resolution deviate
      from the ideal. The reconstruction quality becomes inconsistent throughout the
      image due to the data under sampling caused by the finite resolution of the
      detector. The extension to the multi-projection mode effectively fills-in the
      missing data space and improves the ability to reconstruct an object. This work
      demonstrates the possibility to obtain images in the presence of noise. 

PMID- 24463391
TI  - Ventricular hemodynamics using cardiac computed tomography and optical flow
      method.
AB  - Ventricular hemodynamics plays an important role in assessing cardiac function in
      clinical practice. The aim of this study was to determine the ventricular
      hemodynamics based on contrast movement in the left ventricle (LV) between the
      phases in a cardiac cycle recorded using an electrocardiography (ECG) with
      cardiac computed tomography (CT) and optical flow method. Cardiac CT data were
      acquired at 120 kV and 280 mA with a 350 ms gantry rotation, which covered one
      cardiac cycle, on the 640-slice CT scanner with ECG for a selected patient
      without heart disease. Ventricular hemodynamics (mm/phase) were calculated using
      the optical flow method based on contrast changes with ECG phases in anterior
      posterior, lateral and superior-inferior directions. Local hemodynamic
      information of the LV with color coating was presented. The visualization of the
      functional information made the hemodynamic observation easy. 

PMID- 24463392
TI  - Phloem transport in trees.

PMID- 24463393
TI  - Health literacy predicts pediatric dosing accuracy for liquid zidovudine.
AB  - OBJECTIVES: Little is known about adult caregivers' ability to accurately dose
      pediatric antiretroviral medications. We aimed to characterize the frequency of
      dosing errors for liquid zidovudine using two dosing devices and to evaluate the
      association between HIV literacy and dosing errors in adults living with HIV
      infection. DESIGN: Cross-sectional study enrolling 316 adults receiving
      combination antiretroviral therapy (cART) for HIV infection in Maputo Province,
      Mozambique. METHODS: Participants were administered the HIV Literacy Test (HIV
      LT) and asked to measure 2.5 ml of liquid zidovudine using both a cup and
      syringe. Dosing measurement errors for liquid zidovudine were defined as 'any
      error' (>= 20% deviation from reference dose) and 'major error' (>= 40% deviation
      from reference dose). RESULTS: Dosing errors were common using the cup (any
      error: 50%, major error: 28%) and syringe (any error: 48% of participants, major
      error: 28%). There were no significant differences in proportions of any dosing
      error (P=0.61) or major dosing errors (P=0.82) between dosing instruments. In
      multivariable models, associations (P <= 0.03) were found between higher HIV-LT
      score and dosing errors for both the cup [any error adjusted odds ratio, AOR:
      0.91 (0.84-0.99), major error AOR: 0.84 (0.75-0.92)] and syringe [any error AOR:
      0.82 (0.75-0.90), major error AOR: 0.88 (0.80-0.97)]. CONCLUSION: Liquid
      antiretroviral medications are critical for prevention and treatment of pediatric
      HIV infections, yet dosing errors were exceedingly common in this population and
      were significantly associated with lower HIV literacy levels. Targeted
      interventions are needed to improve HIV knowledge and skills for pediatric
      medication dosing, particularly for caregivers with limited literacy.

PMID- 24463394
TI  - Resistance mutations against dolutegravir in HIV integrase impair the emergence
      of resistance against reverse transcriptase inhibitors.
AB  - OBJECTIVE: Among 1222 antiretroviral-naive patients who received dolutegravir
      (DTG) as part of first-line therapy, none has developed resistance against this
      compound after 48-96 weeks of follow-up. Moreover, only four occurrences of
      virological failure with resistance mutations have been documented in previously
      drug-experienced patients who received DTG as a first time integrase inhibitor as
      a component of a second-line regimen. The R263K integrase resistance mutation was
      observed in two of these individuals who received suboptimal background regimens.
      We have previously selected mutations at position R263K, G118R, H51Y, and E138K
      as being associated with low-level resistance to DTG. Now, we sought to
      investigate the facility with which resistance on the part of R263K-containing
      viruses might develop. DESIGN AND METHODS: We tested the ability of DTG-resistant
      viruses containing either the R263K or G118R and/or H51Y mutations to develop
      further resistance against several reverse transcriptase inhibitors during in
      vitro selection experiments. RESULTS: Our results show that DTG-resistant viruses
      are impaired in their ability to acquire further resistance to each of nevirapine
      and lamivudine as a consequence of their relative inability to develop resistance
      mutations associated with these two compounds. CONCLUSION: Our findings provide
      an explanation for the fact that no individual has yet progressed to virological
      failure with resistance mutations associated with dolutegravir in clinical trials
      in which patients received dolutegravir together with an optimized background
      regimen.

PMID- 24463395
TI  - 20S proteasome as novel biological target for organochalcogenanes.
AB  - A series of hypervalent selenium- and tellurium-containing compounds
      (organoselenuranes and organotelluranes) was evaluated aiming novel inhibitors of
      a threonine protease, namely the 20S proteasome (20S PT). In vitro assays
      demonstrated high inhibitory potency and specificity of these compounds toward
      the beta2 catalytic site of the 20S PT. Organotelluranes were identified as more
      potent inhibitors than organoselenuranes since their IC50 ranged from 3.5 to 16
      MUM while for organoselenuranes the IC50 ranged from 16 to 35 MUM indicating
      great potential to be explored in 20S proteasome inhibition. Cellular assays with
      those compounds were employed to verify the cytotoxicity and ability to inhibit
      20S proteasome in cell. These assays demonstrated that organoselenuranes are
      capable of maintaining their selectivity in cell while the organotelluranes
      became inactive under cellular conditions. Stability studies of the
      organochalcogenanes were performed by (77)Se and (125)Te NMR analysis. It was
      observed that organotelluranes are stable under enzymatic assay conditions and,
      organoselenuranes, the structures responsible for inhibitory activity are
      cyclized organoselenuranes. 

PMID- 24463397
TI  - Preparation and characterization of [Gd(hfac)3(DTBN)(H2O)] (DTBN = di-t-butyl
      nitroxide). Ferromagnetic Gd(3+)-Gd3+ super-superexchange.
AB  - The intramolecular radical-Gd antiferromagnetic coupling (2J1/k(B) = -11.6 K) is
      notably strong, as expected from our molecular design, and the intermolecular
      exchange coupling along the Gd-O-H...O-Gd bridges is unexpectedly ferromagnetic
      with the largest Gd...Gd coupling ever known (2J2/k(B) = +0.12 K).

PMID- 24463396
TI  - The impact of personalized risk feedback on Mexican Americans' perceived risk for
      heart disease and diabetes.
AB  - Little is known about the effect of personalized risk information on risk
      perceptions over time, particularly among ethnically diverse subpopulations. The
      present study examines Mexican American's (MAs) risk perceptions for heart
      disease and diabetes at baseline and following receipt of risk feedback based on
      family health history. Participants comprising 162 households received a pedigree
      or personalized risk feedback, with or without behavioral risk reduction
      recommendations. Multiple logistic regression analyses were used to assess
      lifetime perceived risk (LPR) at baseline, 3 months and 10 months following the
      receipt of risk feedback. Having an elevated familial risk of heart disease or
      diabetes increased the odds of an elevated LPR for both diseases at baseline. At
      3 months, compared with receipt of a pedigree only, MAs receiving elevated risk
      feedback for both diseases were more likely to have an elevated LPR for both
      diseases. At 10 months, participants receiving weak risk feedback for both
      diseases indicated an adjustment to a lower LPR for heart disease only. Results
      suggest that communicating risk for multiple diseases may be more effective than
      a single disease, with responses to increased risk feedback more immediate than
      to weak risk feedback. 

PMID- 24463398
TI  - Ultra performance liquid chromatography/quadrupole-time-of-flight mass
      spectrometry for determination of avicularin metabolites produced by a human
      intestinal bacterium.
AB  - Intestinal bacteria from human were screened to isolate the specific bacteria
      involved in the metabolism of avicularin. A Gram-positive anaerobic bacterium,
      strain 46, capable of metabolizing avicularin (quercetin-3-O-arabinoside) was
      isolated for the first time. Its 16S rRNA gene sequence showed 99% similarity
      with that of Bacillus. Then strain 46 was identified as a species of the genus
      Bacillus, and was named to be Bacillus sp. 46. Additionally, the metabolites were
      analyzed by ultra performance liquid chromatography/quadrupole-time-of-flight
      mass spectrometry (UPLC/Q-TOF-MS) technique combined with MetabolynxTM software.
      The structure of these metabolites were proposed and confirmed by comparing the
      UPLC retention time and MS/MS spectrum with that of authentic standards. Parent
      compound and six metabolites were detected in the isolated bacterial samples
      compared with blank samples. Avicularin (M1) was anaerobic metabolized to its
      aglycone quercetin (M2) and methoxylated avicularin (M3, M4), then quercetin was
      converted to quercetin glycosides: quercetin-3-O-rhamnoside (M5), quercetin-3-O
      glucoside (M6) and quercetin-7-O-glucoside (M7) by Bacillus sp. 46. The metabolic
      pathway and metabolites of avicularin by the intestinal bacterium Bacillus sp. 46
      were reported for the first time. 

PMID- 24463399
TI  - Simultaneous determination of some phthalate metabolites, parabens and
      benzophenone-3 in urine by ultra high pressure liquid chromatography tandem mass
      spectrometry.
AB  - Phthalates, parabens and 2-hydroxy-4-methoxybenzophenone or benzophone-3 are
      thought to act as endocrine disrupting chemicals, being able to disrupt the
      endocrine balance and therefore able to lead to some hormonal diseases. Numerous
      large-scale biomonitoring studies have detected the biomarkers of these compounds
      in more than 75% of the general population. To assess the exposure to these
      chemicals, we developed an analytical method based on a Solid Phase Extraction
      (SPE) prior to ultra high pressure liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS) for the simultaneous measurement of seven phthalate metabolites
      (monobenzyl phthalate, mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-2
      ethylhexyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5
      oxohexyl phthalate, monoethyl phthalate), four parabens (methyl paraben, ethyl
      paraben, n-propyl paraben, n-butyl parabens) and benzophenone-3 in human urine.
      The distinction between unconjugated, glucuro- and sulfoconjugated forms was
      achieved using different enzymatic hydrolyses. The whole procedure was validated
      according to the total error approach, and was demonstrated to be linear
      (regression coefficient ranging from 0.987 to 0.998) and accurate (inter and
      intra assay precision <17.71%, relative bias <5.87%) in the dosing range of
      concentrations. The limits of quantification (LOQs) obtained ranged between 0.30
      and 1.23ng/ml depending on the analyte. The reliability of the method was proven
      in passing successfully the German External Quality Assessment Scheme (G-EQUAS).
      Moreover, the urine from 25 volunteers were analyzed for the determination of
      glucuro-, sulfo- and free species separately. Phthalate metabolites, parabens and
      benzophenone-3 were positively detected in almost all urine samples, with
      detection rates ranging from 40 to 100%. Levels measured ranged from <LOQ to
      2207ng/ml varying widely depending on the compound and the individual. In our
      small participating population, most of the phthalate metabolites were excreted
      predominately as glucuroconjugated forms while parabens and benzophenone-3 were
      detected as glucuro- and sulfoconjugated species in variable proportions
      according to the target compound. 

PMID- 24463400
TI  - Single-domain antibody-based ligands for immunoaffinity separation of recombinant
      human lactoferrin from the goat lactoferrin of transgenic goat milk.
AB  - Single-domain antibody generation technology was applied to make new Sepharose
      bound ligands for affinity separation of closely related proteins, such as human
      and goat lactoferrin. We generated recombinant antibodies that can selectively
      bind/recognize only lactoferrins having amino acid sequences identical to that of
      human natural lactoferrin (anti-hLF Ab). Selected and purified histidine-tagged
      single-domain antibodies were used as ligands, and different lactoferrins were
      used as analytes in the kinetics analysis of lactoferrin binding to captured anti
      hLF Abs using the Bio-Rad ProteOn XPR36 protein interaction array system. The
      data obtained were consistent with a 1:1 binding model with very high affinity,
      practically equal in the case of hLF and rec-hLF (calculated KD varied from
      0.43nM to 3.7nM). Interaction of captured fsdAbs with goat LF was significantly
      weaker and not detectable under the same analysis conditions. We demonstrated the
      high efficiency of the recombinant human lactoferrin purification from goat
      lactoferrin and other proteins using the obtained single domain antibody-based
      affinity ligands. We believe this approach can be used for the generation of
      single-domain antibody-based affinity media for the efficient
      separation/purification of a wide spectrum of other highly homologous proteins. 

PMID- 24463401
TI  - HPLC-UV analysis of thymidine and deoxyuridine in plasma of patients with
      thymidine phosphorylase deficiency.
AB  - We present a simple, fast and validated method for the determination of the two
      nucleosides thymidine (dThd) and deoxyuridine (dUrd) in plasma of patients with
      symptoms suggestive of mitochondrial neurogastrointestinal encephalomyopathy
      (MNGIE), using high performance liquid chromatography coupled with ultraviolet
      spectrophotometric detection (HPLC-UV). Plasma sample (100MUL) pretreatment was
      based on simple deproteinization by 1.2M perchloric acid, using theophylline as
      internal standard (I.S.). HPLC-UV analysis was carried out on a Synergi 4MUm
      Hydro-RP, 150*4mm I.D. column, at room temperature. The mobile phase was a
      mixture of potassium dihydrogen phosphate buffer (20mM, pH 4.5) and acetonitrile
      (95:5, v/v), at an isocratic flow rate of 0.7mL/min. The UV detector was set at
      267nm. The chromatographic run lasted 19min. Similar pyrimidine nucleotides and
      nucleosides do not interfere with the assay. Calibration curves were linear for
      both dThd and dUrd over a range of 0.5 to 5.0MUg/mL. The limit of quantitation
      was 0.5MUg/mL for both nucleosides and the absolute recovery was >90% for dThd,
      dUrd and the I.S. Both intra- and inter-assay precision and accuracy were lower
      than 10% at all tested concentrations. The proposed method was successfully
      applied to measure plasma concentrations of dThd and dUrd in two MNGIE patients.
      This assay simplifies both plasma pretreatment and chromatographic conditions of
      previously reported procedures and describes the first validated method for the
      determination of the two nucleotides in human plasma. 

PMID- 24463402
TI  - Simultaneous quantification of idelalisib, fludarabine and lenalidomide in rat
      plasma by using high-performance liquid chromatography coupled with heated
      electrospray ionization tandem mass spectrometry.
AB  - A sensitive and reliable high-performance liquid chromatography-mass spectrometry
      (LC-MS/MS) method was developed and validated for simultaneous quantification of
      idelalisib, fludarabine and lenalidomide using tolbutamide as an internal
      standard. Analytes were recovered by liquid-liquid extraction and separated on a
      reverse phase C18 column (150mm*4.6mm i.d., 5MUm) using methanol:0.1% formic acid
      buffer (70:30) as mobile phase at a flow rate of 1mL/min in isocratic mode.
      Selective reaction monitoring was performed using the transitions, i.e. m/z
      416.25/176.48, 286.11/154.10, 260.15/149.15, and 271.14/155.06 to quantify
      idelalisib, fludarabine and lenalidomide and tolbutamide, respectively. The
      method was validated over the concentration range of 1.15-576.84ng/mL for
      idelalisib, 0.95-476.25ng/mL for fludarabine and 0.97-486.19ng/mL for
      lenalidomide. Intra and inter-day accuracy and precision of validated method were
      within the acceptable limits of <15%. Coefficients of correlation (r(2)) for the
      calibration curves were >0.998 for all analytes. The method was successfully
      applied for simultaneous estimation of idelalisib, fludarabine and lenalidomide
      in a pharmacokinetic study in rats. 

PMID- 24463403
TI  - Novel germanetellones: XYGe=Te (X, Y = H, F, Cl, Br, I and CN) - structures and
      energetics. Comparison with the first synthetic successes.
AB  - No stable germanetellone was described until Tbt(Dis)Ge=Te and Tbt(Tip)Ge=Te (Tbt
      = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl, Dis = bis(trimethylsilyl)methyl
      and Tip = 2,4,6-triisopropylphenyl) were reported in 1997. Following these
      initial experiments, there has arisen considerable interest in Ge[double bond,
      length as m-dash]Te systems. An obvious question is: why have the simple XYGe=Te
      (X, Y = H, F, Cl, Br, I and CN) molecules not yet been isolated? In view of the
      present situation, theoretical information may be of great help for further
      advances in germanetellone chemistry. A systematic investigation of the XYGe=Te
      molecules is carried out using the second order Moller-Plesset perturbation
      theory (MP2) and density functional theory (DFT). The structures and energetics,
      including ionization potentials (IPad and IPad(ZPVE)), four different forms of
      neutral-anion separations (EAad, EAad(ZPVE), VEA and VDE) and the singlet-triplet
      gaps, are reported. The electronegativity (chi) reactivity descriptor for the
      halogens (F, Cl, Br and I) and the natural charge separations of the Ge=Te moiety
      are used to assess the interrelated properties of germanetellone and its
      derivatives. The results are analyzed, discussed and compared with analogous
      studies of telluroformaldehyde, silanetellone and their derivatives. The
      thermodynamic viabilities of some of the novel germanetellones have also been
      evaluated in terms of the bond dissociation enthalpies of Tbt(Dis)Ge=Te and
      Tbt(Tip)Ge=Te. The simple mono-substituted germanetellones appear to be slightly
      more thermodynamically favored than Tbt(Dis)Ge=Te and Tbt(Tip)Ge=Te, since the
      bond dissociation enthalpies of these kinetically stabilized germanetellones are
      about 28 and 51 kcal mol(-1) lower, respectively.

PMID- 24463404
TI  - Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions
      between PEGylated lipid nanoparticles and biological fluids: from nanostructure
      to uptake in cancer cells.
AB  - When nanoparticles (NPs) enter a physiological environment, medium components
      compete for binding to the NP surface leading to formation of a rich protein
      shell known as the "protein corona". Unfortunately, opsonins are also adsorbed.
      These proteins are immediately recognized by the phagocyte system with rapid
      clearance of the NPs from the bloodstream. Polyethyleneglycol (PEG) coating of
      NPs (PEGylation) is the most efficient anti-opsonization strategy. Linear chains
      of PEG, grafted onto the NP surface, are able to create steric hindrance,
      resulting in a significant inhibition of protein adsorption and less recognition
      by macrophages. However, excessive PEGylation can lead to a strong inhibition of
      cellular uptake and less efficient binding with protein targets, reducing the
      potential of the delivery system. To reach a compromise in this regard we
      employed a multi-component (MC) lipid system with uncommon properties of cell
      uptake and endosomal escape and increasing length of PEG chains. Nano liquid
      chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS) analysis
      allowed us to accurately determine the corona composition showing that
      apolipoproteins are the most abundant class in the corona and that increasing the
      PEG length reduced the protein adsorption and the liposomal surface affinity for
      apolipoproteins. Due to the abundance of apolipoproteins, we exploited the
      "protein corona effect" to deliver cationic liposome-human plasma complexes to
      human prostate cancer PC3 cells that express a high level of scavenger receptor
      class B type 1 in order to evaluate the cellular uptake efficiency of the systems
      used. Combining laser scanning confocal microscopy with flow cytometry analysis
      in PC3 cells we demonstrated that MC-PEG2k is the best compromise between an anti
      opsonization strategy and active targeting and could be a promising candidate to
      treat prostate cancer in vivo. 

PMID- 24463405
TI  - Primary lymphoepithelioma-like carcinoma of the lung: distinct computed
      tomography features and associated clinical outcomes.
AB  - PURPOSE: The aim of the study was to describe the clinical and computed
      tomography (CT) findings of primary lymphoepithelioma-like carcinoma (LELC) of
      the lung. MATERIALS AND METHODS: The clinical data and CT findings of 35 patients
      with histologically proven primary LELC of the lung were retrospectively
      reviewed. The clinical data included age, sex, smoking history, signs and
      symptoms, tumor location, tumor size, stage, Epstein-Barr virus (EBV)-encoded
      small nuclear RNA status, treatment, and outcomes. Pretreatment CT scans of the
      thorax were used to access the tumor site, size, contour, density, vascular
      and/or bronchial involvement, relationship with pleura, and lymphadenopathy.
      RESULTS: The distinct clinical features of primary lung LELC include no
      significant predilection for sex, minimal association with a history of smoking,
      strong association with EBV in Asians, and a predilection for early or locally
      advanced stage of the disease. Most patients received complete resection and/or
      chemotherapy and radiotherapy. The 2- and 5-year overall survival rates for all
      patients were 81% and 51%, respectively. The common CT findings of primary lung
      LELC include peripheral nodules that have direct contact with the adjacent
      pleural surface, with a lesion density that is homogenous and sometimes
      heterogenous. CONCLUSIONS: Radiologists should consider the diagnosis of LELC
      when encountering solitary peripheral pulmonary nodules that have direct contact
      with the pleural surface in EBV endemic areas, and an EBV-encoded small nuclear
      RNA test should be performed on histologic specimens of patients meeting these
      clinical criteria.

PMID- 24463406
TI  - Left atrial volume in chronic obstructive pulmonary disease.
AB  - PURPOSE: The aim of the study was to evaluate left atrial (LA) volume in smokers
      according to the severity of emphysema, with the objective of providing indirect
      evidence of reduced pulmonary venous return due to capillary destruction.
      MATERIALS AND METHODS: A total of 121 smokers underwent a high-pitch and high
      temporal resolution computed tomography (CT) angiographic examination, enabling
      quantification of emphysema, total lung volume, and LA volume measurements
      normalized to body surface area. RESULTS: The CT phenotypes were as follows:
      emphysema predominant (group 1; n=57); airway predominant (group 2; n=30); a
      mixed pattern of emphysema and airway disease (group 3; n=15); and absence of
      bronchopulmonary CT abnormalities (group 4; n=19). A negative correlation was
      found between the indexed LA volume and the percentage of emphysema: (a) in the
      overall study group (P=0.032; r=-0.19); (b) in group 1 (P=0.0163; r=-0.32); and
      (c) in groups 1 and 3 when analyzed together (P=0.0492; r=-0.23). A negative
      correlation was found between the indexed LA volume and the total lung volume in
      the overall study group (P=0.039; r=-0.19) and in group 1 (P=0.048; r=-0.26),
      whereas no correlations were found in group 2 (P=0.44; r=-0.15), group 3 (P=0.52;
      r=-0.17), and groups 1 and 3 analyzed as a whole (P=0.14; r=-0.17). CONCLUSIONS:
      The indexed LA volume, impacting left ventricular preload, is correlated to the
      severity of emphysema.

PMID- 24463407
TI  - Rapid quantification of microalgal lipids in aqueous medium by a simple
      colorimetric method.
AB  - Identification of novel microalgal strains with high lipid productivity is one of
      the most important research topics in renewable biofuel research. However, the
      major bottleneck in the strain screening process is that currently known methods
      for the estimation of microalgal lipid are laborious and time-consuming. The
      present study successfully employed sulpho-phospho-vanillin (SPV) colorimetric
      method for direct quantitative measurement of lipids within liquid microalgal
      culture. The SPV reacts with lipids to produce a distinct pink color, and its
      intensity can be quantified using spectrophotometric methods by measuring
      absorbance at 530nm. This method was employed for a rapid quantification of
      intracellular lipid contents within Chlorella sp., Monoraphidium sp., Ettlia sp.
      and Nannochloropsis sp., all of which were found to have lipid contents ranging
      in between 10% and 30%. Subsequent analysis of the biomass using gas
      chromatography confirmed that our protocol is highly accurate (R(2)=0.99). 

PMID- 24463409
TI  - Autohydrolysis of Miscanthus x giganteus for the production of
      xylooligosaccharides (XOS): kinetics, characterization and recovery.
AB  - The optima conditions of production and purification of xylooligosaccharides
      (XOS) from Miscanthus x giganteus (MxG) were investigated. Using autohydrolysis,
      XOS were produced at 160, 180 and 200 degrees C at 60, 20 and 5min, respectively.
      XOS yield up to 13.5% (w/w) of initial biomass and 69.2% (w/w) of xylan were
      achieved. Results from HPAEC-PAD analysis revealed that X1-X9 sugar oligomers
      were produced. Higher temperature and longer reaction time resulted in lower
      product molecular weight. The three optimum conditions had similar degrees of
      polymerization XOS. Using 10% activated carbon (w/v) with ethanol/water elution
      recovered 47.9% (w/w) of XOS from pretreated liquid phase. The XOS could be
      fractionated by degree of polymerization according to ethanol concentration in
      the ethanol/water elution. Most of the XOS were washed out in 30% and 50%
      ethanol/water (v/v) fractions. Recoveries of 91.8% xylobiose, 86.9% xylotriose,
      66.3% xylotetrose, 56.2% xylopentose and 48.9% xylohexaose were observed in XOS. 

PMID- 24463408
TI  - Biocrude yield and productivity from the hydrothermal liquefaction of marine and
      freshwater green macroalgae.
AB  - Six species of marine and freshwater green macroalgae were cultivated in outdoor
      tanks and subsequently converted to biocrude through hydrothermal liquefaction
      (HTL) in a batch reactor. The influence of the biochemical composition of biomass
      on biocrude yield and composition was assessed. The freshwater macroalgae
      Oedogonium afforded the highest biocrude yield of all six species at 26.2%, dry
      weight (dw). Derbesia (19.7%dw) produced the highest biocrude yield for the
      marine species followed by Ulva (18.7%dw). In contrast to significantly different
      yields across species, the biocrudes elemental profiles were remarkably similar
      with higher heating values of 33-34MJkg(-1). Biocrude productivity was highest
      for marine Derbesia (2.4gm(-2)d(-1)) and Ulva (2.1gm(-2)d(-1)), and for
      freshwater Oedogonium (1.3gm(-2)d(-1)). These species were therefore identified
      as suitable feedstocks for scale-up and further HTL studies based on biocrude
      productivity, as a function of biomass productivity and the yield of biomass
      conversion to biocrude. 

PMID- 24463410
TI  - Reducing cofactors contribute to the increase of butanol production by a wild
      type Clostridium sp. strain BOH3.
AB  - Availability of reducing factors (e.g., NADH and NADPH) plays an important role
      in improving the efficacy of products conversion in cofactor-dependent production
      systems. In this study, nicotinic acid (NA), the precursor of NADH and NADPH, was
      supplemented to the growth medium of a wild-type Clostridium sp. strain BOH3.
      Results showed that the addition of precursor NA to the medium led to a
      significant increase in the levels of NADH and NADPH. Meanwhile, a maximal cell
      growth rate and butanol generation rate were reached by applying a two-stage pH
      shift strategy, achieving 18.7g/L butanol with a yield of 24.6% and a
      productivity of 0.26g/Lh. The metabolic patterns were shifted towards more
      reduced metabolites as reflected by higher butanol-to-acetone ratio (11%) and
      butanol-to-acid ratio (292%). Redistributing metabolic flux to butanol via
      manipulations of reducing cofactor and pH shift could become an alternative tool
      to realize metabolic engineering goals. 

PMID- 24463411
TI  - Kinetics of SO(2)-ethanol-water (SEW) fractionation of hardwood and softwood
      biomass.
AB  - SO(2)-ethanol-water (SEW) fractionation of forest residues (tree tops, stumps,
      branches) was investigated to demonstrate the potential of this method for forest
      biorefineries. The effect of fractionation time on dissolution of wood components
      was studied. Total mass balances of fractionation show that lignin and
      hemicelluloses are rapidly dissolved in the spent fractionation liquor whereas
      cellulose is fully preserved in the solid residue throughout the fractionation
      treatment. Within 20min treatment at 150 degrees C (SO(2):EtOH:H2O=12:43.5:44.5,
      by weight, L:W ratio 6Lkg(-1)), 89% of hardwood lignin and 74% of hemicelluloses
      are dissolved. The corresponding values for softwood biomass are 64% and 74%,
      respectively, indicating slower delignification but equal hemicellulose removal.
      Additionally, sulfur content of the feedstocks, solid fractionation residues and
      spent liquors were analyzed to determine the degree of lignin sulfonation. The
      obtained results are compared with the stem wood fractionation results.

PMID- 24463412
TI  - Using pig manure to promote fermentation of sugarcane molasses alcohol wastewater
      and its effects on microbial community structure.
AB  - Molasses alcohol wastewater (MAW) is difficult to be bio-treated and converted
      into biogas. In this study, MAW mixed with pig manure (PM) in different ratios
      was co-digested. Biogas production, chemical oxygen demand (COD) removal and the
      structure of microbial communities were monitored in the process. Our results
      showed that under the optimal COD ratio of PM:MAW (1.0:1.5), CODremoval and
      biogas yield were the highest. And in fermentation tanks with different PM to MAW
      ratios, the structure and composition of bacterial communities varied in the
      early and late stage. Furthermore, the type of main bacterial operational
      taxonomic units (OTUs) have no differences, yet the relative abundance of OTUs
      varied. The current research showed that there was a good potential to the use of
      PM as a co-digested material to anaerobic treatment of MAW and provided
      references for further improving bio-treatment of MAW. 

PMID- 24463414
TI  - Enhanced disinfection of wastewater by combining wetland treatment with
      bioelectrochemical H(2)O(2) production.
AB  - A highly-loaded constructed wetland (up to 44+/-21gCODm(-2)d(-1)) was connected
      to a bioelectrochemical system (BES) to produce hydrogen peroxide for
      disinfection purposes. The anode delivered a current from the wetland effluent up
      to 3.5Am(-2) (maximum 62% anodic efficiency) but was limited in the supply of
      organic carbon. Hydrogen peroxide could be produced in situ in wetland effluent.
      Production rates were tested at various current densities with a maximum rate of
      2.7gmelectrode(-2)h(-1) (4h at 10Am(-2), 41% cathodic efficiency). Little
      difference was observed between production rate in wetland effluent or a 0.3%
      NaCl solution. The resulting hydrogen peroxide (0.1%) was used to disinfect
      wetland effluent successfully (<75CFUml(-1) after 1h contact time). The
      combination of wetland water treatment with peroxide production in a BES thus
      enables generating higher water qualities, including disinfected water, without
      external input of chemicals. 

PMID- 24463415
TI  - [Complications in hearing aid fitting without otolaryngologist expertise].
AB  - BACKGROUND: Hearing loss is a symptom. The underlying disease must be
      investigated by an otolaryngologist, in order to ensure timely identification of
      alterations in disease course, complications and newly occurring secondary
      disease. METHODS: During the course of 1 year, 484 case studies in which
      treatment errors had arisen due to lack of otolaryngologist involvement during
      hearing aid fitting were collected from 115 practices and 7 ENT clinics, as well
      as from the patient representatives of the Federal Joint Committee. Depending on
      the type and cause of the individual complications, these were classified into
      five groups and described cumulatively. RESULTS: A total of 484 cases in which
      results had been incorrectly interpreted or charged to the wrong payer
      organization were presented in the form of a systematic overview. Furthermore,
      serious technical deficits, as well as unnecessary temporary and inappropriate
      fittings were observed. CONCLUSION: The aforementioned cases are interpreted on
      the basis of regulations governing hearing aid fitting and current legal
      practices. These case reports clearly demonstrate that otolaryngologist expertise
      are required not only at the first hearing aid fitting, but also for subsequent
      fittings, in order to appropriately treat the underlying disease. Only so can the
      patient be protected from damage to their health and financial complications, and
      health insurance providers avoid wasting resources.

PMID- 24463413
TI  - Performance and microbial community dynamics in a two-phase anaerobic co
      digestion system using cassava dregs and pig manure.
AB  - The two-phase anaerobic co-digestion of cassava dregs (CD) with pig manure (PM)
      was evaluated using four sequencing batch reactors (SBRs) and a continuously
      stirred tank reactor (CSTR). The effect of seven different PM to CD volatile
      solid ratios (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10) on the acidification phase
      was investigated. Results indicated the concentrations of soluble chemical oxygen
      demand, NH4-N and volatile fatty acids increased substantially at seven ratios.
      Co-acidification of PM and CD performed well. Methanogenic fermentation of the
      acidification products at seven ratios was steady in CSTR. The highest methane
      yield and VS removal of 0.352m(3)/kg VSadded and 68.5% were achieved at PM:CD
      (4:6). The microbial population in CSTR was analyzed using molecular methods.
      Findings revealed that bacteria such as Firmicutes and Bacteroidetes, archaea
      such as Methanobacteriales and Methanomicrobiales were advantageous populations.
      Co-digestion of PM and CD supported higher quantity and diversity of methanogens.

PMID- 24463416
TI  - The effect of cataract extraction on intraocular pressure.
AB  - PURPOSE OF REVIEW: To examine the current literature covering the long-term
      effect of cataract extraction on intraocular pressure (IOP). RECENT FINDINGS: As
      a result of the high rate of cataract surgery, the impact on IOP continues to be
      the subject of multiple studies in different populations. Recent publications
      include those that distinguish patients with open angles from those with more
      narrow angles, as well as prospective analyses that address the impact of
      regression to the mean and other types of bias on the effect of postoperative IOP
      lowering. SUMMARY: There are sufficient data to suggest that cataract surgery
      provides a lowering effect on IOP in the long term. This effect appears to be
      proportional to preoperative IOP. Eyes with higher preoperative IOP have the
      greatest average lowering, whereas eyes with IOP in the lower range of
      statistically normal tend to have an IOP that is unchanged from baseline or even
      higher following cataract surgery. In patients with narrow angles, the IOP
      lowering effect appears to also be proportional to the degree of anterior chamber
      deepening induced by cataract surgery.

PMID- 24463418
TI  - Evidence-based management of primary angle closure glaucoma.
AB  - PURPOSE OF REVIEW: To review the classification of primary angle closure (PAC)
      and discuss the evidence-based management of each type. RECENT FINDINGS: There is
      limited evidence to support the prophylactic treatment of primary angle closure
      suspects. Cataract and clear lens extraction may be more effective than
      traditional therapy in controlling intraocular pressure (IOP) in patients with
      PAC, primary angle closure glaucoma, and acute angle closure crisis. SUMMARY:
      Treatment of angle closure depends on the signs of chronic angle damage and
      glaucomatous optic neuropathy. In the absence of such evidence, serial gonioscopy
      may be the preferred therapy. If signs or symptoms are present, medical therapy
      and laser peripheral iridotomy are beneficial. However, recent data suggest that
      cataract extraction may be more effective at controlling the IOP than laser or
      incisional glaucoma procedures.

PMID- 24463417
TI  - Complications of tube implants and their management.
AB  - PURPOSE OF REVIEW: The use of glaucoma drainage devices (GDD) in the treatment of
      glaucoma has become widely accepted for cases of refractory glaucoma. Expansion
      in the indications for implantation of GDD beyond refractory glaucoma is
      increasingly common. As such, tube implant complications are reviewed to aid in
      prevention and improve their management. RECENT FINDINGS: Findings of the Tube
      Versus Trabeculectomy study resulted in an expanded use of tube implants in cases
      of refractory glaucoma. As interest in GDD implantation flourished, so too, did
      investigative comparison between devices; which includes the Ahmed Baerveldt
      Comparison study and Ahmed Verses Baerveldt study. Comparative analysis of
      success and complication rates between implantable devices is not only expanding
      the technology of tube implants, but also building a body of evidence that tube
      implantation has a strong safety profile and usage among specialists will
      continue to increase and indications will evolve. Complications resulting from
      GDD implantation include hypotony, postoperative elevated intraocular pressure,
      tube erosion, diplopia, motility disturbances, and corneal decompensation.
      SUMMARY: Tube implant use is increasing and indications are expanding beyond
      refractory glaucoma. Understanding differences in GDD, their complications and
      management will result in improved patient care.

PMID- 24463419
TI  - Sustained drug delivery in glaucoma.
AB  - PURPOSE OF REVIEW: This article reviews recently published studies and important
      clinical trials of novel drug delivery systems for glaucoma and evaluates the
      potential of these systems to provide sustained therapeutic benefits. RECENT
      FINDINGS: The efficacy of topical medications to lower intraocular pressure (IOP)
      is limited by poor patient adherence, low bioavailability of drug and the
      potential for local and systemic side effects. Recent studies highlight the
      potential for sustained drug delivery through innovative delivery platforms.
      Nanoparticle-based formulations, drug-eluting contact lenses, punctum inserts and
      bioadhesive matrices placed in the conjunctival sac can enhance drug delivery by
      increasing precorneal residence time, enhancing corneal permeation and lowering
      the systemic absorption of drug. Periocular injections and surgically implanted
      drug reservoirs could offer even greater duration of drug delivery, particularly
      when the drug is packaged within stable vehicles. SUMMARY: Novel platforms for
      providing sustained drug delivery in glaucoma continue to evolve. The ability to
      incorporate effective commercially available drugs into more stable compounds is
      an important element. Although more research is needed to establish their
      clinical efficacy, novel delivery systems will allow for more targeted medical
      therapy and for the opportunity to further explore neuroprotective and gene-based
      therapies.

PMID- 24463420
TI  - Bacterial physiology: tracking persisters in vivo.

PMID- 24463421
TI  - Effectiveness of web-based tailored advice on parents' child safety behaviors:
      randomized controlled trial.
AB  - BACKGROUND: Injuries at home are a major cause of death, disability, and loss of
      quality of life among young children. Despite current safety education, required
      safety behavior of parents is often lacking. To prevent various childhood
      disorders, the application of Web-based tools has increased the effectiveness of
      health promotion efforts. Therefore, an intervention with Web-based, tailored,
      safety advice combined with personal counseling (E-Health4Uth home safety) was
      developed and applied. OBJECTIVE: To evaluate the effect of E-Health4Uth home
      safety on parents' safety behaviors with regard to the prevention of falls,
      poisoning, drowning, and burns. METHODS: A randomized controlled trial was
      conducted (2009-2011) among parents visiting well-baby clinics in the
      Netherlands. Parents were randomly assigned to the intervention group (E
      Health4Uth home safety intervention) or to the control condition consisting of
      usual care. Parents in the intervention condition completed a Web-based safety
      behavior assessment questionnaire; the resulting tailored safety advice was
      discussed with their child health care professional at a well-baby visit (age
      approximately 11 months). Parents in the control condition received counseling
      using generic safety information leaflets at this well-baby visit. Parents' child
      safety behaviors were derived from self-report questionnaires at baseline (age 7
      months) and at follow-up (age 17 months). Each specific safety behavior was
      classified as safe/unsafe and a total risk score was calculated. Logistic and
      linear regression analyses were used to reveal differences in safety behavior
      between the intervention and the control condition at follow-up. RESULTS: A total
      of 1292 parents (response rate 44.79%) were analyzed. At follow-up, parents in
      the intervention condition (n=643) showed significantly less unsafe behavior
      compared to parents in the control condition (n=649): top of staircase (23.91%
      vs. 32.19%; OR 0.65, 95% CI 0.50-0.85); bottom of staircase (63.53% vs. 71.94%;
      OR 0.69, 95% CI 0.53-0.88); top and bottom of staircase (68.94% vs. 78.28%; OR
      0.62, 95% CI 0.48-0.81); storage of cleaning products (30.33% vs. 39.91%; OR
      0.67, 95% CI 0.53-0.85); bathing of the child (23.46% vs. 32.25%; OR 0.65, 95% CI
      0.51-0.84); drinking hot fluids (34.84% vs. 41.73%; OR 0.76, 95% CI 0.61-0.96);
      using rear hotplates (79.34% vs. 85.27%; OR 0.67, 95% CI 0.50-0.90); and the
      total risk score in which a higher score indicates more unsafe behavior (mean
      13.63, SD 6.12 vs. mean 15.34, SD 6.07; beta -1.59, 95% CI -2.26 to -0.93). There
      were no significant differences for other specific behaviors between the two
      study conditions. CONCLUSIONS: Compared to generic written materials, the E
      Health4Uth home safety intervention seems more effective in promoting parents'
      safety behavior for safe staircases, storage of cleaning products, bathing,
      drinking hot fluids, and cooking. This study supports the application of Web
      based, tailored, safety advice for the prevention of unintentional injuries in
      the youth health care setting. TRIAL REGISTRATION: Nederlands Trial Register:
      NTR1836; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1836 (Archived
      by WebCite at http://www.webcitation.org/6MPIGQxpx).

PMID- 24463422
TI  - Olmsted syndrome caused by a homozygous recessive mutation in TRPV3.

PMID- 24463423
TI  - No increased risk of fetal death or prolonged time to pregnancy in women with
      psoriasis.

PMID- 24463425
TI  - Ocular vestibular-evoked myogenic potentials (oVEMP) to skull taps in normal and
      dehiscent ears: mechanisms and markers of superior canal dehiscence.
AB  - The site of stimulus delivery modulates the waveforms of cervical- and ocular
      vestibular-evoked myogenic potentials (cVEMP and oVEMP) to skull taps in healthy
      controls. We examine the influence of stimulus location on the oVEMP waveforms of
      18 patients (24 ears) with superior canal dehiscence (SCD) and compare these with
      the results of 16 healthy control subjects (32 ears). oVEMPs were recorded in
      response to taps delivered with a triggered tendon-hammer and a hand-held
      minishaker at three midline locations; the hairline (Fz), vertex (Cz) and occiput
      (Oz). In controls, Fz stimulation evoked a consistent oVEMP waveform with a
      negative peak (n1) at 9.5 +/- 0.5 ms. In SCD, stimulation at Fz produced large
      oVEMP waveforms with delayed n1 peaks (tendon-hammer = 13.2 +/- 1.0 ms and
      minitap = 11.5 +/- 1.1 ms). Vertex taps produced diverse low-amplitude waveforms
      in controls with n1 peaks at 15.5 +/- 1.2 and 13.2 +/- 1.3 ms for tendon-hammer
      taps and minitaps, respectively; in SCD, they produced large amplitude oVEMP
      waveforms with n1 peaks at 12.9 +/- 0.8 ms (tendon-hammer) and 12.1 +/- 0.5 ms
      (minitap). Occiput stimulation evoked oVEMPs with similar n1 latencies in both
      groups (tendon-hammer = 11.3 +/- 1.3 and 10.7 +/- 0.8; minitap = 10.3 +/- 0.9 and
      11.1 +/- 0.4 for control and SCD ears, respectively). Compared to reflex
      amplitudes, n1 peak latencies to Fz taps provided clearer separation between SCD
      and control ears. The distinctly different effects of Fz and vertex taps on the
      oVEMP waveforms may represent an additional non-osseous mechanism of stimulus
      transmission in SCD. For skull taps at Fz, a prolonged n1 latency is an indicator
      of SCD.

PMID- 24463424
TI  - Elevated circulation levels of an antiangiogenic SERPIN in patients with diabetic
      microvascular complications impair wound healing through suppression of Wnt
      signaling.
AB  - Wound healing, angiogenesis, and hair follicle maintenance are often impaired in
      the skin of diabetic patients, but the pathogenesis has not been well understood.
      Here, we report that circulation levels of kallistatin, a member of the serine
      proteinase inhibitor (SERPIN) superfamily with antiangiogenic activities, were
      elevated in type 2 diabetic patients with diabetic vascular complications. To
      test the hypothesis that elevated kallistatin levels could contribute to a wound
      healing deficiency via the inhibition of Wnt/beta-catenin signaling, we generated
      kallistatin-transgenic (KS-TG) mice. KS-TG mice had reduced cutaneous hair
      follicle density, microvascular density, and panniculus adiposus layer thickness,
      as well as altered skin microvascular hemodynamics and delayed cutaneous wound
      healing. Using Wnt reporter mice, our results showed that Wnt/beta-catenin
      signaling is suppressed in the dermal endothelium and hair follicles in KS-TG
      mice. Lithium, a known activator of beta-catenin via inhibition of glycogen
      synthase kinase-3beta, reversed the inhibition of Wnt/beta-catenin signaling by
      kallistatin and rescued the wound-healing deficiency in KS-TG mice. These
      observations suggest that elevated circulating antiangiogenic serpins in diabetic
      patients may contribute to impaired wound healing through inhibition of Wnt/beta
      catenin signaling. Activation of Wnt/beta-catenin signaling, at a level
      downstream of Wnt receptors, may ameliorate the wound-healing deficiency in
      diabetic patients. 

PMID- 24463426
TI  - Direction detection thresholds of passive self-motion in artistic gymnasts.
AB  - In this study, we compared direction detection thresholds of passive self-motion
      in the dark between artistic gymnasts and controls. Twenty-four professional
      female artistic gymnasts (ranging from 7 to 20 years) and age-matched controls
      were seated on a motion platform and asked to discriminate the direction of
      angular (yaw, pitch, roll) and linear (leftward-rightward) motion. Gymnasts
      showed lower thresholds for the linear leftward-rightward motion. Interestingly,
      there was no difference for the angular motions. These results show that the
      outstanding self-motion abilities in artistic gymnasts are not related to an
      overall higher sensitivity in self-motion perception. With respect to vestibular
      processing, our results suggest that gymnastic expertise is exclusively linked to
      superior interpretation of otolith signals when no change in canal signals is
      present. In addition, thresholds were overall lower for the older (14-20 years)
      than for the younger (7-13 years) participants, indicating the maturation of
      vestibular sensitivity from childhood to adolescence.

PMID- 24463427
TI  - Teen mothers at midlife: the long shadow of adversarial family caregiving.
AB  - Despite keen interest in teen mothers' outcomes, few studies have followed teen
      mothers prospectively or examined how outcomes are shaped by family relationships
      and practices over time. This multigenerational, hermeneutic study began 21 years
      ago when 16 families were interviewed after the teen's infant reached 8 to 10
      months of age. Families were re-interviewed every 4 to 5 years. This article
      describes the 3 families who exemplified adversarial caregiving at the first
      study and how their relationships unfolded and shaped long-term outcomes.
      Findings alert clinicians to the importance of recognizing red flags and
      intervening early to interrupt adversarial caregiving. 

PMID- 24463428
TI  - Expression and purification of a GRAS domain of SLR1, the rice DELLA protein.
AB  - GRAS proteins belong to a plant specific protein family that participates in
      diverse and important functions in growth and development. GRAS proteins are
      typically composed of a variable N-terminal domain and highly conserved C
      terminal GRAS domain. Despite the importance of the GRAS domain, little
      biochemical or structural analyses have been reported, mainly due to difficulties
      with purification of sufficient quality and quantity of protein. This study is
      focused on one of the most extensively studied GRAS proteins, the rice DELLA
      protein (SLR1), which is known to be involved in gibberellin (GA) signaling.
      Using a baculovirus-insect cell expression system we have achieved overproduction
      and purification of full-length SLR1. Limited proteolysis of the full-length SLR1
      indicated that a region including the entire GRAS domain (SLR1(206-625)) is
      protease resistant. Based on those results, we have constructed an expression and
      purification system of the GRAS domain (SLR1(206-625)) in Escherichia coli.
      Several physicochemical assays have indicated that the folded structure of the
      GRAS domain is rich in secondary structural elements and that alanine
      substitutions for six cysteine residues improves protein folding without
      impairing function. Furthermore, by NMR spectroscopy we have observed direct
      interaction between the purified GRAS domain and the GA receptor GID1. Taken
      together, our purified preparation of the GRAS domain of SLR1 is suitable for
      further structural and functional studies that will contribute to precise
      understanding of the plant regulation mechanism through DELLA and GRAS proteins. 

PMID- 24463429
TI  - Simultaneous quantification of mitochondrial DNA copy number and deletion ratio:
      a multiplex real-time PCR assay.
AB  - Mitochondrial dysfunction is implicated in a vast array of diseases and
      conditions, such as Alzheimer's disease, cancer, and aging. Alterations in
      mitochondrial DNA (mtDNA) may provide insight into the processes that either
      initiate or propagate this dysfunction. Here, we describe a unique multiplex
      assay which simultaneously provides assessments of mtDNA copy number and the
      proportion of genomes with common large deletions by targeting two mitochondrial
      sites and one nuclear locus. This probe-based, single-tube multiplex provides
      high specificity while eliminating well-to-well variability that results from
      assaying nuclear and mitochondrial targets individually. 

PMID- 24463430
TI  - Damage evaluation based on a wave energy flow map using multiple PZT sensors.
AB  - A new wave energy flow (WEF) map concept was proposed in this work. Based on it,
      an improved technique incorporating the laser scanning method and Betti's
      reciprocal theorem was developed to evaluate the shape and size of damage as well
      as to realize visualization of wave propagation. In this technique, a simple
      signal processing algorithm was proposed to construct the WEF map when waves
      propagate through an inspection region, and multiple lead zirconate titanate
      (PZT) sensors were employed to improve inspection reliability. Various damages in
      aluminum and carbon fiber reinforced plastic laminated plates were experimentally
      and numerically evaluated to validate this technique. The results show that it
      can effectively evaluate the shape and size of damage from wave field variations
      around the damage in the WEF map. 

PMID- 24463431
TI  - SoundCompass: a distributed MEMS microphone array-based sensor for sound source
      localization.
AB  - Sound source localization is a well-researched subject with applications ranging
      from localizing sniper fire in urban battlefields to cataloging wildlife in rural
      areas. One critical application is the localization of noise pollution sources in
      urban environments, due to an increasing body of evidence linking noise pollution
      to adverse effects on human health. Current noise mapping techniques often fail
      to accurately identify noise pollution sources, because they rely on the
      interpolation of a limited number of scattered sound sensors. Aiming to produce
      accurate noise pollution maps, we developed the SoundCompass, a low-cost sound
      sensor capable of measuring local noise levels and sound field directionality.
      Our first prototype is composed of a sensor array of 52 Microelectromechanical
      systems (MEMS) microphones, an inertial measuring unit and a low-power field
      programmable gate array (FPGA). This article presents the SoundCompass's hardware
      and firmware design together with a data fusion technique that exploits the
      sensing capabilities of the SoundCompass in a wireless sensor network to localize
      noise pollution sources. Live tests produced a sound source localization accuracy
      of a few centimeters in a 25-m2 anechoic chamber, while simulation results
      accurately located up to five broadband sound sources in a 10,000-m2 open field. 

PMID- 24463432
TI  - Child and setting characteristics affecting the adult talk directed at
      preschoolers with autism spectrum disorder in the inclusive classroom.
AB  - Difficulty with social competence is a core deficit of autism spectrum disorder.
      Research on typically developing children and children with disabilities, in
      general, suggests the adult talk received in the classroom is related to their
      social development. The aims of this study were to examine (1) the types and
      amounts of adult talk children with autism spectrum disorder are exposed to in
      the preschool classroom and (2) the associations between child characteristics
      (e.g. language), activity area, and adult talk. Kontos' Teacher Talk
      classification was used to code videos approximately 30 min in length of 73
      children with autism spectrum disorder (ages 3-5) in inclusive classrooms (n =
      33) during center time. The results indicated practical/personal assistance was
      the most common type of adult talk coded, and behavior management talk least
      often coded. Child characteristics (i.e. age and autism severity) and activity
      area were found to be related to specific types of adult talk. Given the
      findings, implications for future research are discussed. 

PMID- 24463433
TI  - Examining the criterion-related validity of the Pervasive Developmental Disorder
      Behavior Inventory.
AB  - The Pervasive Developmental Disorder Behavior Inventory is a questionnaire
      designed to aid in the diagnosis of pervasive developmental disorders or autism
      spectrum disorders. The Pervasive Developmental Disorder Behavior Inventory
      assesses adaptive and maladaptive behaviors associated with pervasive
      developmental disorders and provides an age-standardized Autism Composite score.
      In previous research, the Pervasive Developmental Disorder Behavior Inventory has
      demonstrated moderate to strong reliability and validity. This study aimed to
      replicate and extend previous research by investigating the criterion-related
      validity of the Pervasive Developmental Disorder Behavior Inventory. Data from 40
      children were analyzed in relation to other measures. The Pervasive Developmental
      Disorder Behavior Inventory adaptive scores were moderately correlated with
      cognitive and adaptive behavior scores as expected. However, no significant
      correlations were found between the maladaptive and Autism Composite scores of
      the Pervasive Developmental Disorder Behavior Inventory and the Childhood Autism
      Rating Scale. Results lead to concerns regarding the validity of some scores of
      the Pervasive Developmental Disorder Behavior Inventory. 

PMID- 24463434
TI  - Improving transportability of a cognitive-behavioral treatment intervention for
      anxiety in youth with autism spectrum disorders: results from a US-Canada
      collaboration.
AB  - Anxiety disorders frequently co-occur in youth with autism spectrum disorders. In
      addition to developing efficacious treatments for anxiety in children with autism
      spectrum disorders, it is important to examine the transportability of these
      treatments to real-world settings. Study aims were to (a) train clinicians to
      deliver Facing Your Fears: Group Therapy for Managing Anxiety in Children with
      High-Functioning Autism Spectrum Disorders to fidelity and (b) examine
      feasibility of the program for novel settings. A secondary aim was to examine
      preliminary youth treatment outcome. Results indicated that clinicians obtained
      excellent fidelity following a workshop and ongoing consultation. Acceptability
      ratings indicated that Facing Your Fears Therapy was viewed favorably, and
      critiques were incorporated into program revisions. Meaningful reductions in
      anxiety were reported posttreatment for 53% of children. Results support the
      initial effectiveness and transportability of Facing Your Fears Therapy in new
      clinical settings. 

PMID- 24463435
TI  - Antioxidant activity and interaction with DNA and albumins of zinc-tolfenamato
      complexes. Crystal structure of [Zn(tolfenamato)2(2,2'-dipyridylketoneoxime)2].
AB  - The zinc(II) complex of the non-steroidal anti-inflammatory drug tolfenamic acid
      (=Htolf) in the presence of 2,2'-dipyridylketone oxime (=Hpko) as a N,N'-donor
      heterocyclic ligand, [Zn(tolf-O)2(Hpko-N,N')2].MeOH (=1.MeOH), has been
      synthesized and characterized by physicochemical techniques including X-ray
      crystallography. The complex exhibits good binding affinity to human or bovine
      serum albumin with high binding constant values. Complex 1 and previously
      reported Zn-tolfenamato complexes were tested for their free radical scavenging
      activity and in vitro inhibitory activity against soybean lipoxygenase and
      exhibited significant activity with [Zn(tolf)2(1,10-phenantroline)] being the
      most active compound. The complexes interact with calf-thymus (CT) DNA via
      intercalation, and can displace the DNA-bound ethidium bromide with 1 exhibiting
      the highest binding constant to CT DNA.

PMID- 24463436
TI  - Syntheses and evaluation of drug-like properties of CO-releasing molecules
      containing ruthenium and group 6 metal.
AB  - In this paper, drug-like properties of two series of carbonyl metal CO-releasing
      molecules, Ru(CO)3Cl(n)L (n=1, L=amino acid or its derivatives 1-7,
      L=acetylacetone 8 or 2,2'-bipyridyl 9; n=2, L=aminopyridine derivatives 10-13;
      n=0, L=salicylaldehyde Schiff base 14-15) and M(CO)5L(M=Cr, Mo, W; L=glycine
      methyl ester 16-18; L=N-methyl imidazole 19-21), were preliminarily evaluated
      from four aspects involving in cytotoxicity, in vivo toxicity, bio-distribution
      and metabolism. Cytotoxic effects of all complexes were assayed by MTT. IC50
      values of complexes 1-15 were 39.55-240.16mg/l, and those of complexes 16 and 18
      were 21.36-22.21 mg/l. Toxicity tests of mice used oral acute toxic class method
      and got LD50 values of some complexes; among them, LD50 of complex 1 was in 800
      1000 mg/kg, complex 7 in 1100-1500 mg/kg and complex 18 in 75-125 mg/kg. After
      several consecutive administrations, tested complexes severely damaged liver and
      kidney in both functional and morphological aspects. And by metal ions
      measurements using ICP-AES, we found that the tested complexes were unevenly
      distributed in tissues and organs. In vivo, Ru(II) in complexes was oxidized to
      Ru(III) by P450 enzymes, and for Mo(0) and W(0) in complexes, part of them
      transformed into higher oxidation state, the others kept original state.

PMID- 24463437
TI  - Microwave induced three-component synthesis and antimycobacterial activity of
      benzopyrazolo[3,4-b]quinolindiones.
AB  - Three series of novel 4-arylbenzo[h]pyrazolo[3,4-b]quinolin-5,6-diones 4, 7 and 9
      have been efficiently obtained in good yields by three-component microwave
      assisted reaction between aminopyrazoles 1 or 6 (both 1-phenyl and 1-H
      substituted), 2-hydroxynaphthoquinone 2 and benzaldehydes 3. Compounds 4, 7 and 9
      have been evaluated against fifteen Mycobacterium spp strains, and six of them
      have shown antimycobacterial activity. The highest inhibitory activity with MIC
      <=2 MUg/mL for three of these compounds (4a, 4b and 4g) was related with their
      highest lipophilicity and lesser polarity within these series.

PMID- 24463438
TI  - Clinical trials: what are we afraid of, what should we do?

PMID- 24463439
TI  - Distal aspiration with retrievable stent assisted thrombectomy for the treatment
      of acute ischemic stroke.
AB  - OBJECTIVE: Flexible large lumen aspiration catheters and stent retrievers have
      recently become available in the USA for the revascularization of large vessel
      occlusions presenting within the context of acute ischemic stroke (AIS). We
      describe a multicenter experience using a combined aspiration and stent retrieval
      technique for thrombectomy. DESIGN: A retrospective analysis to identify patients
      receiving combined manual aspiration and stent retrieval for treatment of AIS
      between August 2012 and April 2013 at six high volume stroke centers was
      conducted. Outcome variables, including recanalization rate, post-treatment
      National Institutes of Health Stroke Scale (NIHSS) score, symptomatic
      intracranial hemorrhage, discharge 90 day modified Rankin Scale (mRS) score, and
      mortality were evaluated. RESULTS: 105 patients were found that met the inclusion
      criteria for this retrospective study. Successful recanalization (Thrombolysis in
      Cerebral Infarction score 2B) was achieved in 92 (88%) of these patients. 44% of
      patients had favorable (mRS score 0-2) outcomes at 90 days. There were five
      (4.8%) symptomatic intracerebral hemorrhages and three procedure related deaths
      (2.9%). CONCLUSIONS: Mechanical thrombectomy utilizing combined manual aspiration
      with a stent retriever is an effective and safe strategy for endovascular
      recanalization of large vessel occlusions presenting within the context of AIS.

PMID- 24463440
TI  - Contrast-enhanced time-resolved MRA for pre-angiographic evaluation of suspected
      spinal dural arterial venous fistulas.
AB  - BACKGROUND: Spinal digital subtraction angiography (DSA) is the gold standard for
      diagnosis of spinal dural arterial venous fistulas (SDAVFs), but can require
      extensive time, radiation exposure and contrast dose. We hypothesize that
      contrast-enhanced time-resolved MR angiography (CE-TR MRA) will have utility for
      the non-invasive diagnosis and pre-angiographic localization of SDAVFs. METHODS:
      Eighteen patients underwent both CE-TR MRA and DSA for suspected SDAVFs, with DSA
      performed a median of 11 days (range 0-41) after MRA. CE-TR MRA was performed on
      a 1.5 T GE unit using Time Resolved Imaging of Contrast Kinetics (TRICKS). CE-TR
      MRA and DSA images were evaluated for the presence of SDAVFs and location of the
      feeding arterial supply, with DSA as the reference standard. DSA was also
      evaluated for the number of vessels catheterized, contrast volume and
      fluoroscopic and procedure times. RESULTS: Eight of the 18 patients were positive
      for SDAVF on DSA. Sensitivity, specificity, positive predictive value and
      negative predictive value for the 18 CE-TR MRAs were 88%, 90%, 88% and 90%,
      respectively. Localization of the SDAVF arterial supply on CE-TR MRA was within
      one vertebral level from DSA for 6/7 SDAVFs. Compared with patients with a SDAVF
      and feeding artery identified on CE-TR MRA, patients with negative or suboptimal
      CE-TR MRA had a significantly increased number of vessels catheterized (p=0.027)
      and larger contrast volumes (p=0.022). CONCLUSIONS: CE-TR MRA is a useful initial
      examination for the diagnosis and localization of SDAVFs, with a high concordance
      rate with DSA. When CE-TR MRA demonstrates a SDAVF, the number of catheterized
      vessels and contrast dose can be decreased during DSA.

PMID- 24463441
TI  - Treatment of posterior uveal melanoma with multi-dose photodynamic therapy.
AB  - AIMS: To report on the use of multi-dose photodynamic therapy (PDT) in the
      treatment of posterior uveal melanoma. METHODS: Prospective case series. 18
      patients with posterior uveal melanoma were treated with a minimum of three
      sessions of PDT. Mean tumour thickness was 1.92 mm (median 1.75, range 0.5-4.4
      mm) while the mean basal diameter was 7.1 mm (median 6.3, range 5.2-11 mm).
      Patients were assessed for visual acuity, complications, tumour status and
      systemic metastases. RESULTS: In 16 cases, the tumour regressed with stable or
      improved vision in 15 patients (83%) over a mean follow-up period of 28 months
      (median 26.5, range 12-44 months). One patient developed an edge recurrence on
      two occasions ultimately requiring proton beam therapy while one patient showed
      no response to PDT before being successfully treated with proton beam therapy.
      Two patients developed scleritis requiring a short course of systemic steroids.
      No patient developed metastatic disease in the study period. CONCLUSIONS:
      Posterior uveal melanomas may be successfully treated with high dose PDT with
      retention of good vision in the majority of cases, at least in the short-term.
      Longer follow-up is required to see if these encouraging results are maintained.

PMID- 24463442
TI  - At last: classification of human mammary cells elucidates breast cancer origins.
AB  - Current breast cancer classification systems are based on molecular evaluation of
      tumor receptor status and do not account for distinct morphological phenotypes.
      In other types of cancer, taxonomy based on normal cell phenotypes has been
      extremely useful for diagnosis and treatment strategies. In this issue of the
      JCI, Santagata and colleagues developed a breast cancer classification scheme
      based on characterization of healthy mammary cells. Reclassification of breast
      cancer cells and breast cancer tissue microarrays with this system correlated
      with prognosis better than the standard receptor status designation. This scheme
      provides a major advance toward our understanding of the origin of the cells in
      the breast and breast cancers. 

PMID- 24463443
TI  - Lipids rule: resetting lipid metabolism restores T cell function in systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a devastating autoimmune disease
      characterized by chronic inflammation and systemic destruction of host organs or
      tissue. A key feature of SLE is T cell dysfunction characterized by
      hyperresponsive antigen receptor signaling. In this issue of the JCI, McDonald
      and colleagues provide evidence that homeostasis of a subset of lipids, the
      glycosphingolipids (GSLs), is severely perturbed in the membranes of T cells from
      SLE patients. Furthermore, normalization of GSLs restored TCR signaling and
      ameliorated T cell dysfunction. These data suggest that targeting host metabolism
      may be an effective means of reinforcing self-tolerance and attenuating
      autoimmunity. 

PMID- 24463444
TI  - Osteogenesis imperfecta in adults.
AB  - A 42-year-old premenopausal woman with osteogenesis imperfecta presents to the
      metabolic bone clinic. She has a daughter with osteogenesis imperfecta who is
      seen regularly in a specialist pediatric clinic, but the patient herself hasn't
      had a clinical consultation in years. She has pain and stiffness in her back and
      is worried for her future bone health. The patient asks, "Am I going to fall
      apart?" She had numerous fractures in childhood, including fractures of her femur
      and wrist; fractured her ankles several times in her late teens; and had
      occasional fractures in adulthood. Her last fracture was a comminuted fracture of
      her humerus three years ago, when she stumbled and fell forward onto her hands
      and knees. The woman is hyperextensible and thinks her ankles feel weak. Her bone
      mineral density T scores are -2.6 at the lumbar spine and -1.9 at the total hip,
      and spine imaging shows several vertebral endplate deformities, but overall
      preservation of vertebral height. What are the available pharmacological and
      nonpharmacological strategies to preserve her skeletal health and function? 

PMID- 24463445
TI  - An unexpected role for platelets in blocking Th17 differentiation.
AB  - It is well known that platelets interact with cells of the innate immune system
      to promote tissue repair. In contrast, it is less clear whether these links
      extend to cells of the adaptive immune system, such as T cells. In this issue of
      the JCI, Morrell and colleagues provide compelling evidence that platelets are
      required to limit CD4+ Th17 differentiation through the actions of the chemokine
      platelet factor 4 (PF4). Absence of PF4 in the host leads to exaggerated Th17
      differentiation after transplantation and rapid graft rejection. The authors'
      findings argue that platelets are not bit part players, but rather fully fledged,
      critical members of the adaptive immune system. 

PMID- 24463446
TI  - Paradoxical insights into whole body metabolic adaptations following SGLT2
      inhibition.
AB  - It is well known that glycemic control over time reduces microvascular and
      macrovascular complications in human subjects with type 2 diabetes. In addition,
      preclinical models of type 2 diabetes have demonstrated that long-term
      hyperglycemia exacerbates insulin resistance and reduces beta cell function;
      therefore, therapies that reduce blood glucose levels are of great interest in
      not only controlling complications, but for restoring known defects in the
      pathogenesis of type 2 diabetes. Pharmacological inhibition of the sodium-glucose
      cotransporter 2 (SGLT2) reduces plasma glucose by limiting glucose absorption in
      the kidney and increasing glucose excretion in the urine. In this issue of the
      JCI, Merovci and colleagues and Ferrannini and colleagues independently report a
      paradoxical increase in endogenous glucose production in patients with type 2
      diabetes following SGLT2 inhibition, despite an overall decrease in fasting
      plasma glucose. Together, these studies provide a unique insight into the effects
      of SGLT2 inhibition on whole body metabolism. 

PMID- 24463447
TI  - Normalizing glycosphingolipids restores function in CD4+ T cells from lupus
      patients.
AB  - Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE)
      have multiple defects in lymphocyte signaling and function that contribute to
      disease pathogenesis. Such defects could be attributed to alterations in
      metabolic processes, including abnormal control of lipid biosynthesis pathways.
      Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile
      of lipid raft-associated glycosphingolipids (GSLs) compared with that of healthy
      controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and
      monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated
      GSLs in SLE patients were associated with increased expression of liver X
      receptor beta (LXRbeta), a nuclear receptor that controls cellular lipid
      metabolism and trafficking and influences acquired immune responses. Stimulation
      of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR
      agonists promoted GSL expression, which was blocked by an LXR antagonist.
      Increased GSL expression in CD4+ T cells was associated with intracellular
      accumulation and accelerated trafficking of GSL, reminiscent of cells from
      patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in
      vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized
      GSL metabolism, corrected CD4+ T cell signaling and functional defects, and
      decreased anti-dsDNA antibody production by autologous B cells in SLE patients.
      Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis
      and suggest that targeting GSL biosynthesis restores T cell function in SLE. 

PMID- 24463448
TI  - Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose
      production.
AB  - Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which
      can be ameliorated in animal models by inducing glucosuria with renal glucose
      transport inhibitors. Here, we examined whether reduction of plasma glucose with
      a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated
      tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men
      were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2
      weeks. We measured insulin-mediated whole body glucose uptake and endogenous
      glucose production (EGP) at baseline and 2 weeks after treatment using the
      euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced
      glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue
      glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin
      treatment, while placebo-treated subjects had no change in insulin sensitivity.
      Surprisingly, following dapagliflozin treatment, EGP increased substantially and
      was accompanied by an increase in fasting plasma glucagon concentration.
      Together, our data indicate that reduction of plasma glucose with an agent that
      works specifically on the kidney to induce glucosuria improves muscle insulin
      sensitivity. However, glucosuria induction following SGLT2 inhibition is
      associated with a paradoxical increase in EGP. These results provide support for
      the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs
      insulin action in individuals with type 2 diabetes. 

PMID- 24463449
TI  - NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution
      following myelosuppressive radiation.
AB  - A nuclear disaster may result in exposure to potentially lethal doses of ionizing
      radiation (IR). Hematopoietic acute radiation syndrome (H-ARS) is characterized
      by severe myelosuppression, which increases the risk of infection, bleeding, and
      mortality. Here, we determined that activation of nuclear factor erythroid-2
      related factor 2 (NRF2) signaling enhances hematopoietic stem progenitor cell
      (HSPC) function and mitigates IR-induced myelosuppression and mortality.
      Augmenting NRF2 signaling in mice, either by genetic deletion of the NRF2
      inhibitor Keap1 or by pharmacological NRF2 activation with 2-trifluoromethyl-2'
      methoxychalone (TMC), enhanced hematopoietic reconstitution following bone marrow
      transplantation (BMT). Strikingly, even 24 hours after lethal IR exposure, oral
      administration of TMC mitigated myelosuppression and mortality in mice.
      Furthermore, TMC administration to irradiated transgenic Notch reporter mice
      revealed activation of Notch signaling in HSPCs and enhanced HSPC expansion by
      increasing Jagged1 expression in BM stromal cells. Administration of a Notch
      inhibitor ablated the effects of TMC on hematopoietic reconstitution. Taken
      together, we identified a mechanism by which NRF2-mediated Notch signaling
      improves HSPC function and myelosuppression following IR exposure. Our data
      indicate that targeting this pathway may provide a countermeasure against the
      damaging effects of IR exposure. 

PMID- 24463450
TI  - Taxonomy of breast cancer based on normal cell phenotype predicts outcome.
AB  - Accurate classification is essential for understanding the pathophysiology of a
      disease and can inform therapeutic choices. For hematopoietic malignancies, a
      classification scheme based on the phenotypic similarity between tumor cells and
      normal cells has been successfully used to define tumor subtypes; however, use of
      normal cell types as a reference by which to classify solid tumors has not been
      widely emulated, in part due to more limited understanding of epithelial cell
      differentiation compared with hematopoiesis. To provide a better definition of
      the subtypes of epithelial cells comprising the breast epithelium, we performed a
      systematic analysis of a large set of breast epithelial markers in more than
      15,000 normal breast cells, which identified 11 differentiation states for normal
      luminal cells. We then applied information from this analysis to classify human
      breast tumors based on normal cell types into 4 major subtypes, HR0-HR3, which
      were differentiated by vitamin D, androgen, and estrogen hormone receptor (HR)
      expression. Examination of 3,157 human breast tumors revealed that these HR
      subtypes were distinct from the current classification scheme, which is based on
      estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor 2. Patient outcomes were best when tumors expressed all 3 hormone
      receptors (subtype HR3) and worst when they expressed none of the receptors
      (subtype HR0). Together, these data provide an ontological classification scheme
      associated with patient survival differences and provides actionable insights for
      treating breast tumors. 

PMID- 24463451
TI  - Evaluation of teriparatide treatment in adults with osteogenesis imperfecta.
AB  - BACKGROUND: Adults with osteogenesis imperfecta (OI) have a high risk of
      fracture. Currently, few treatment options are available, and bone anabolic
      therapies have not been tested in clinical trials for OI treatment. METHODS: 79
      adults with OI were randomized to receive 20 MUg recombinant human parathyroid
      hormone (teriparatide) or placebo for 18 months in a double-blind, placebo
      controlled trial. The primary endpoint was the percent change in areal bone
      mineral density (aBMD) of the lumbar spine (LS), as determined by dual-energy X
      ray absorptiometry. Secondary endpoints included percent change in bone
      remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed
      tomography, estimated vertebral strength by finite element analysis, and self
      reported fractures. RESULTS: Compared with the placebo group, the teriparatide
      group showed increased LS aBMD (6.1% +/- 1.0% vs. 2.8% +/- 1.0% change from
      baseline; P < 0.05) and total hip aBMD (2.6% +/- 1.0% vs. -2.4% +/- 1.0% change;
      P < 0.001). Vertebral vBMD and strength improved with teriparatide therapy (18%
      +/- 6% and 15% +/- 3% change, respectively), but declined with placebo (-5.0% +/-
      6% and -2.0% +/- 3% change; P < 0.05 for both comparisons). Serum procollagen
      type 1 N-terminal propeptide (P1NP) and urine collagen N-telopeptide (NTx) levels
      increased with teriparatide therapy (135% +/- 14% and 64% +/- 10% change,
      respectively). Teriparatide-induced elevation of P1NP levels was less pronounced
      in severe forms of OI (type III/IV) compared with the milder form (type I). Type
      I OI patients exhibited robust BMD increases with teriparatide; however, there
      was no observed benefit for those with type III/IV OI. There was no difference in
      self-reported fractures between the 2 groups. CONCLUSIONS: Adults with OI,
      particularly those with less severe disease (type I), displayed a teriparatide
      induced anabolic response, as well as increased hip and spine aBMD, vertebral
      vBMD, and estimated vertebral strength. Trial registration. Clinicaltrials.gov
      NCT00131469. Funding. The Osteoporosis Imperfecta Foundation, Eli Lilly and Co.,
      the National Center for Advancing Translational Science (NCATS) at the NIH (grant
      no. UL1RR024140), and the Baylor College of Medicine General Clinical Research
      Center (grant no. RR00188).

PMID- 24463452
TI  - Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection.
AB  - Th cells are the major effector cells in transplant rejection and can be divided
      into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by
      transcription factor expression, which is driven by positive and negative
      cytokine and chemokine stimuli at the time of T cell activation. Here we
      discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17
      differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune
      responses to cardiac transplantation, including increased numbers of infiltrating
      Th17 cells and increased plasma IL-17. Although PF4 has been described as a
      platelet-specific molecule, we found that activated T cells also express PF4.
      Furthermore, bone marrow transplantation experiments revealed that T cell-derived
      PF4 contributes to a restriction in Th17 differentiation. Taken together, the
      results of this study demonstrate that PF4 is a key regulator of Th cell
      development that is necessary to limit Th17 differentiation. These data likely
      will impact our understanding of platelet-dependent regulation of T cell
      development, which is important in many diseases, in addition to transplantation.

PMID- 24463453
TI  - Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular
      junction maturation.
AB  - Spinal muscular atrophy is a common motor neuron disease caused by low survival
      motoneuron (SMN), a key protein in the proper splicing of genes. Restoring the
      protein is therefore a promising therapeutic strategy. Implementation of this
      strategy, however, depends on defining the temporal requirements for SMN. Here,
      we used controlled knockdown of SMN in transgenic mice to determine the precise
      postnatal stage requirements for this protein. Reducing SMN in neonatal mice
      resulted in a classic SMA-like phenotype. Unexpectedly, depletion of SMN in
      adults had relatively little effect. Insensitivity to low SMN emerged abruptly at
      postnatal day 17, which coincided with establishment of the fully mature
      neuromuscular junction (NMJ). Mature animals depleted of SMN eventually exhibited
      evidence of selective neuromuscular pathology that was made worse by traumatic
      injury. The ability to regenerate the mature NMJ in aged or injured SMN-depleted
      mice was grossly impaired, a likely consequence of the inability to meet the
      surge in demand for motoneuronal SMN that was seen in controls. Our results
      demonstrate that relative maturity of the NMJ determines the temporal requirement
      for the SMN protein. These observations suggest that the use of potent but
      potentially deleterious SMN-enhancing agents could be tapered in human patients
      once the neuromuscular system matures and reintroduced as needed to enhance SMN
      for remodeling aged or injured NMJs. 

PMID- 24463454
TI  - Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2
      diabetic patients.
AB  - BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glycemia by
      enhancing urinary glucose excretion. The physiologic response to
      pharmacologically induced acute or chronic glycosuria has not been investigated
      in human diabetes. METHODS: We evaluated 66 patients with type 2 diabetes (62 +/-
      7 years, BMI = 31.6 +/- 4.6 kg/m(2), HbA1c = 55 +/- 8 mmol/mol, mean +/- SD) at
      baseline, after a single dose, and following 4-week treatment with empagliflozin
      (25 mg). At each time point, patients received a mixed meal coupled with dual
      tracer glucose administration and indirect calorimetry. RESULTS: Both single-dose
      and chronic empagliflozin treatment caused glycosuria during fasting (median, 7.8
      [interquartile range {IQR}, 4.4] g/3 hours and 9.2 [IQR, 5.2] g/3 hours) and
      after meal ingestion (median, 29.0 [IQR, 12.5] g/5 hours and 28.2 [IQR, 15.4] g/5
      hours). After 3 hours of fasting, endogenous glucose production (EGP) was
      increased 25%, while glycemia was 0.9 +/- 0.7 mmol/l lower (P < 0.0001 vs.
      baseline). After meal ingestion, glucose and insulin AUC decreased, whereas the
      glucagon response increased (all P < 0.001). While oral glucose appearance was
      unchanged, EGP was increased (median, 40 [IQR, 14] g and 37 [IQR, 11] g vs. 34
      [IQR, 11] g, both P < 0.01). Tissue glucose disposal was reduced (median, 75
      [IQR, 16] g and 70 [IQR, 21] g vs. 93 [IQR, 18] g, P < 0.0001), due to a decrease
      in both glucose oxidation and nonoxidative glucose disposal, with a concomitant
      rise in lipid oxidation after chronic administration (all P < 0.01). beta Cell
      glucose sensitivity increased (median, 55 [IQR, 35] pmol * min(-1) * m(-2) * mM(
      1) and 55 [IQR, 39] pmol * min(-1) * m(-2) * mM(-1) vs. 44 [IQR, 32] pmol * min(
      1) * m(-2) * mM(-1), P < 0.0001), and insulin sensitivity was improved. Resting
      energy expenditure rates and those after meal ingestion were unchanged.
      CONCLUSIONS: In patients with type 2 diabetes, empagliflozin-induced glycosuria
      improved beta cell function and insulin sensitivity, despite the fall in insulin
      secretion and tissue glucose disposal and the rise in EGP after one dose, thereby
      lowering fasting and postprandial glycemia. Chronic dosing shifted substrate
      utilization from carbohydrate to lipid. Trial registration. ClinicalTrials.Gov
      NCT01248364 (EudraCT no. 2010-018708-99). Funding. This study was funded by
      Boehringer Ingelheim.

PMID- 24463455
TI  - SMN-targeted therapeutics for spinal muscular atrophy: are we SMArt enough yet?
AB  - Spinal muscular atrophy (SMA) remains one of the most common and lethal autosomal
      recessive diseases. Homozygous deletion of survival of motor neuron 1 (SMN1) and
      resulting SMN protein deficiency manifests predominantly with motor neuron
      degeneration; however, a wealth of emerging data supports a broader influence of
      SMN deficiency in disease pathogenesis. In this issue of the JCI, Kariya and
      colleagues demonstrate the relatively selective impact of SMN depletion on the
      distal motor unit using a series of SMN2-expressing transgenic mice in which
      constitutive SMN knockdown follows variable periods of normal development. Their
      observations provide further insights regarding the temporal requirements for SMN
      in mice, renewing speculation about when and where repletion of SMN is necessary
      for optimal outcomes in SMA patients. 

PMID- 24463456
TI  - Transcriptional profiling reveals differential expression of a neuropeptide-like
      protein and pseudogenes in aryl hydrocarbon receptor-1 mutant Caenorhabditis
      elegans.
AB  - The aryl hydrocarbon receptor (AHR) functions in higher organisms in development,
      metabolism and toxic responses. Its Caenorhabditis elegans (C. elegans) ortholog,
      AHR-1, facilitates neuronal development, growth and movement. We investigated the
      effect of AHR mutation on the transcriptional profile of L4 stage C. elegans
      using RNA-seq and quantitative real time PCR in order to understand better AHR-1
      function at the genomic level. Illumina HiSeq 2000 sequencing yielded 51.1, 61.2
      and 54.0 million reads from wild-type controls, ahr-1(ia03) and ahr-1(ju145)
      mutants, respectively, providing detection of over 18,000 transcripts in each
      sample. Fourteen transcripts were over-expressed and 125 under-expressed in both
      ahr-1 mutants when compared to wild-type. Under-expressed genes included soluble
      guanylate cyclase (gcy) family genes, some of which were previously demonstrated
      to be regulated by AHR-1. A neuropeptide-like protein gene, nlp-20, and a F-box
      domain protein gene fbxa-192 and its pseudogenes fbxa-191 and fbxa-193 were also
      under-expressed. Conserved xenobiotic response elements were identified in the 5'
      flanking regions of some but not all of the gcy, nlp-20, and fbxa genes. These
      results extend previous studies demonstrating control of gcy family gene
      expression by AHR-1, and furthermore suggest a role of AHR-1 in regulation of a
      neuropeptide gene as well as pseudogenes. 

PMID- 24463457
TI  - Host defense peptides from Lithobates forreri, Hylarana luctuosa, and Hylarana
      signata (Ranidae): phylogenetic relationships inferred from primary structures of
      ranatuerin-2 and brevinin-2 peptides.
AB  - The primary structures of host-defense peptides present in frog skin secretions
      constitute useful molecular markers for establishing taxonomic classifications
      and investigating phylogenetic relationships between species within a particular
      genus. Peptidomic analysis has led to the characterization of multiple host
      defense peptides in norepinephrine-stimulated skin secretions of three species of
      frogs from the family Ranidae: Lithobates forreri (Boulenger, 1883), Hylarana
      luctuosa (Peters, 1871), and Hylarana signata (Gunther, 1872). The L. forreri
      secretions contain ranatuerin-2 (2 peptides), brevinin-1 (4 peptides), and
      temporin (1 peptide). The H. luctuosa secretions contain brevinin-2 (4 peptides),
      esculentin-1 (1 peptide), esculentin-2 (1 peptide), palustrin-2 (2 peptides), and
      temporin (2 peptides). The H. signata secretions contain brevinin-2 (4 peptides),
      brevinin-1 (5 peptides), palustrin-2 (1 peptide), and temporin (2 peptides).
      Cladistic analysis based upon the primary structures of 44 ranatuerin-2 peptides
      from 20 Lithobates species indicates a close phylogenetic relationship between L.
      forreri, Lithobates onca, and Lithobates yavapaiensis. A similar cladistic
      analysis based upon the primary structures of 27 brevinin-2 peptides from 8
      Hylarana species provides support for a close phylogenetic relationship between
      H. signata and Hylarana picturata, while showing that the species are not
      conspecific, with H. luctuosa more distantly related. 

PMID- 24463458
TI  - BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and
      clinical impact.
AB  - PURPOSE: Multiple BRAF inhibitor resistance mechanisms have been described,
      however, their relative frequency, clinical correlates, and effect on subsequent
      therapy have not been assessed in patients with metastatic melanoma. EXPERIMENTAL
      DESIGN: Fifty-nine BRAF(V600)-mutant melanoma metastases from patients treated
      with dabrafenib or vemurafenib were analyzed. The genetic profile of resistance
      mechanisms and tumor signaling pathway activity was correlated with
      clinicopathologic features and therapeutic outcomes. RESULTS: Resistance
      mechanisms were identified in 58% progressing tumors and BRAF alterations were
      common. Gene expression analysis revealed that mitogen-activated protein kinase
      (MAPK) activity remained inhibited in 21% of resistant tumors, and the outcomes
      of patients with these tumors were poor. Resistance mechanisms also occurred in
      pretreatment biopsies and heterogeneity of resistance mechanisms occurred within
      patients and within tumors. There were no responses to subsequent targeted
      therapy, even when a progressing tumor had a resistance mechanism predicted to be
      responsive. CONCLUSIONS: Selecting sequential drugs based on the molecular
      characteristics of a single progressing biopsy is unlikely to provide improved
      responses, and first-line therapies targeting multiple pathways will be required.

PMID- 24463459
TI  - Melanoma brain metastasis globally reconfigures chemokine and cytokine profiles
      in patient cerebrospinal fluid.
AB  - The aggressiveness of melanoma is believed to be correlated with tumor-stroma
      associated immune cells. Cytokines and chemokines act to recruit and then
      modulate the activities of these cells, ultimately affecting disease progression.
      Because melanoma frequently metastasizes to the brain, we asked whether global
      differences in immunokine profiles could be detected in the cerebrospinal fluid
      (CSF) of melanoma patients and reveal aspects of tumor biology that correlate
      with patient outcomes. We therefore measured the levels of 12 cytokines and 12
      chemokines in melanoma patient CSF and the resulting data were analyzed to
      develop unsupervised hierarchical clustergrams and heat maps. Unexpectedly, the
      overall profiles of immunokines found in these samples showed a generalized
      reconfiguration of their expression in melanoma patient CSF, resulting in the
      segregation of individuals with melanoma brain metastasis from nondisease
      controls. Chemokine CCL22 and cytokines IL1alpha, IL4, and IL5 were reduced in
      most samples, whereas a subset including CXCL10, CCL4, CCL17, and IL8 showed
      increased expression. Further, analysis of clusters identified within the
      melanoma patient set comparing patient outcome suggests that suppression of
      IL1alpha, IL4, IL5, and CCL22, with concomitant elevation of CXCL10, CCL4, and
      CCL17, may correlate with more aggressive development of brain metastasis. These
      results suggest that global immunokine suppression in the host, together with a
      selective increase in specific chemokines, constitute a predominant
      immunomodulatory feature of melanoma brain metastasis. These alterations likely
      drive the course of this disease in the brain and variations in the immune
      profiles of individual patients may predict outcomes. 

PMID- 24463460
TI  - A single-centre experience of patients with metastatic melanoma enrolled in a
      dabrafenib named patient programme.
AB  - We studied the efficacy, tolerability and clinical courses of dabrafenib in
      patients with metastatic melanoma who were ineligible for enrolment into a
      clinical trial. Between July 2011 and May 2013, patients with unresectable stage
      III or stage IV, V600-mutated metastatic melanoma who were not eligible for
      inclusion into clinical trials were offered treatment with dabrafenib through a
      named patient programme. Routine efficacy and toxicity data were collected
      throughout treatment and studied retrospectively. The endpoints were progression
      free survival (PFS), overall survival and best overall response. Thirty-one
      patients commenced dabrafenib therapy including six individuals who had
      progressed on a prior BRAF-inhibitor treatment. The majority of patients had
      cerebral metastases (n=17) and/or a poor performance status [Eastern Cooperative
      Oncology Group (ECOG)>=2, n=11]. Median overall survival was 5.6 months (range
      0.1-22 months). Median PFS was 3.3 months (range 0.1-21) and was similar despite
      performance status. One patient had a complete response and eight showed partial
      responses to treatment. Patients with cerebral metastases (n=17) had a median PFS
      of 4.6 months. Five patients (16%) had dose-limiting toxicities. Despite several
      poor prognostic features, dabrafenib is a safe and effective treatment in the
      community setting, with occasional impressive outcomes. 

PMID- 24463461
TI  - Melanomas of unknown primary frequently harbor TERT-promoter mutations.
AB  - Commonly, in patients with melanoma metastases of an unknown primary tumor (MUP),
      an extensive search for the primary tumor is carried out. Recently, highly
      recurrent telomerase reverse transcriptase (TERT)-promoter mutations were found
      in malignant melanomas, which may function as driver mutations of skin cancer.
      The aim of this study was to test the hypothesis that MUP and mucosal melanomas
      harbor different prevalences of TERT-promoter mutations. Thirty-nine patients
      with MUP and 53 patients with mucosal melanomas were retrieved. In total, 152
      paraffin samples of 92 patients were analyzed, and in 38 patients, multiple
      samples were tested. Mutational analysis of the TERT-promoter, BRAF, NRAS, and
      KIT genes was carried out. In total, 92 patients were eligible for mutational
      analysis. TERT-promoter mutations were found in 33 patients (35.9%): chr5,
      1,295,228 C>T (18 patients); chr5, 1,295,250 C>T (11 patients); chr5, 1,295,228
      229 CC>TT (three patients); chr5, 1,295,242-243 CC>TT (one patient). The
      mutations were significantly more prevalent in MUP [26 (66.7%)] than in mucosal
      melanomas [seven patients (13.2%); P<0.001]. In MUP, BRAF mutations were found in
      46.2% of patients (18 patients) and NRAS mutations in 28.2% of patients (11
      patients). In mucosal melanoma, NRAS mutations were found in 18.9% of patients
      (10), and BRAF and KIT mutations in 7.5% of patients (four patients),
      respectively. The prevalence of TERT-promoter mutations was associated with the
      patient's sex [23 (51.1%) men, 10 (21.3%) women; P=0.004]. No significant
      correlation was found between TERT-mutation and patient survival. The TERT
      promoter genotype of MUP points toward a cutaneous and not mucosal origin. The
      significant sex differences merit further attention in having putative
      therapeutic implications. 

PMID- 24463462
TI  - Concentration-dependent polyparameter linear free energy relationships to predict
      organic compound sorption on carbon nanotubes.
AB  - Adsorption of organic compounds on carbon nanotubes (CNTs), governed by
      interactions between molecules and CNTs surfaces, is critical for their fate,
      transport, bioavailability and toxicity in the environment. Here, we report a
      promising concentration-dependent polyparameter linear free energy relationships
      (pp-LFERs) model to describe the compound-CNTs interactions and to predict
      sorption behavior of chemicals on CNTs in a wide range of concentrations (over
      five orders of magnitude). The developed pp-LFERs are able to capture the
      dependence of the k(i) on equilibrium concentration. The pp-LFERs indexes [r, p,
      a, b, v] representing different interactions are found to have a good
      relationship with the aqueous equilibrium concentrations of compounds. This
      modified model can successfully interpret the relative contribution of each
      interaction at a given concentration and reliably predict sorption of various
      chemicals on CNTs. This approach is expected to help develop a better
      environmental fate and risk assessment model.

PMID- 24463463
TI  - In vitro membrane reconstitution of the T-cell receptor proximal signaling
      network.
AB  - T-cell receptor (TCR) phosphorylation is controlled by a complex network that
      includes Lck, a Src family kinase (SFK), the tyrosine phosphatase CD45 and the
      Lck-inhibitory kinase Csk. How these competing phosphorylation and
      dephosphorylation reactions are modulated to produce T-cell triggering is not
      fully understood. Here we reconstituted this signaling network using purified
      enzymes on liposomes, recapitulating the membrane environment in which they
      normally interact. We demonstrate that Lck's enzymatic activity can be regulated
      over an ~10-fold range by controlling its phosphorylation state. By varying
      kinase and phosphatase concentrations, we constructed phase diagrams that reveal
      ultrasensitivity in the transition from the quiescent to the phosphorylated state
      and demonstrate that co-clustering TCR and Lck or detaching Csk from the membrane
      can trigger TCR phosphorylation. Our results provide insight into the mechanism
      of TCR signaling as well as other signaling pathways involving SFKs. 

PMID- 24463464
TI  - Topological organization of multichromosomal regions by the long intergenic
      noncoding RNA Firre.
AB  - RNA, including long noncoding RNA (lncRNA), is known to be an abundant and
      important structural component of the nuclear matrix. However, the molecular
      identities, functional roles and localization dynamics of lncRNAs that influence
      nuclear architecture remain poorly understood. Here, we describe one lncRNA,
      Firre, that interacts with the nuclear-matrix factor hnRNPU through a 156-bp
      repeating sequence and localizes across an ~5-Mb domain on the X chromosome. We
      further observed Firre localization across five distinct trans-chromosomal loci,
      which reside in spatial proximity to the Firre genomic locus on the X chromosome.
      Both genetic deletion of the Firre locus and knockdown of hnRNPU resulted in loss
      of colocalization of these trans-chromosomal interacting loci. Thus, our data
      suggest a model in which lncRNAs such as Firre can interface with and modulate
      nuclear architecture across chromosomes. 

PMID- 24463465
TI  - Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate
      deubiquitination during proteasomal degradation.
AB  - Polyubiquitin chains target protein substrates to the 26S proteasome, where they
      are removed by the deubiquitinase Rpn11 to allow efficient substrate degradation.
      Despite Rpn11's essential function during substrate processing, its detailed
      structural and biochemical characterization has been hindered by difficulties in
      purifying the isolated enzyme. Here we report the 2.0-A crystal structures of
      Zn(2+)-free and Zn(2+)-bound Saccharomyces cerevisiae Rpn11 in an MPN-domain
      heterodimer with Rpn8. The Rpn11-Rpn8 interaction occurs via two distinct
      interfaces that may be conserved in related MPN-domain complexes. Our structural
      and mutational studies reveal that Rpn11 lacks a conserved surface to bind the
      ubiquitin Ile44 patch, does not interact with the moiety on the proximal side of
      the scissile isopeptide bond and exhibits no linkage specificity for ubiquitin
      cleavage. These findings explain how Rpn11 functions as a promiscuous
      deubiquitinase for cotranslocational substrate deubiquitination during
      proteasomal degradation. 

PMID- 24463466
TI  - A framework for different levels of integration of computational models into web
      based virtual patients.
AB  - BACKGROUND: Virtual patients are increasingly common tools used in health care
      education to foster learning of clinical reasoning skills. One potential way to
      expand their functionality is to augment virtual patients' interactivity by
      enriching them with computational models of physiological and pathological
      processes. OBJECTIVE: The primary goal of this paper was to propose a conceptual
      framework for the integration of computational models within virtual patients,
      with particular focus on (1) characteristics to be addressed while preparing the
      integration, (2) the extent of the integration, (3) strategies to achieve
      integration, and (4) methods for evaluating the feasibility of integration. An
      additional goal was to pilot the first investigation of changing framework
      variables on altering perceptions of integration. METHODS: The framework was
      constructed using an iterative process informed by Soft System Methodology. The
      Virtual Physiological Human (VPH) initiative has been used as a source of new
      computational models. The technical challenges associated with development of
      virtual patients enhanced by computational models are discussed from the
      perspectives of a number of different stakeholders. Concrete design and
      evaluation steps are discussed in the context of an exemplar virtual patient
      employing the results of the VPH ARCH project, as well as improvements for future
      iterations. RESULTS: The proposed framework consists of four main elements. The
      first element is a list of feasibility features characterizing the integration
      process from three perspectives: the computational modelling researcher, the
      health care educationalist, and the virtual patient system developer. The second
      element included three integration levels: basic, where a single set of
      simulation outcomes is generated for specific nodes in the activity graph;
      intermediate, involving pre-generation of simulation datasets over a range of
      input parameters; advanced, including dynamic solution of the model. The third
      element is the description of four integration strategies, and the last element
      consisted of evaluation profiles specifying the relevant feasibility features and
      acceptance thresholds for specific purposes. The group of experts who evaluated
      the virtual patient exemplar found higher integration more interesting, but at
      the same time they were more concerned with the validity of the result. The
      observed differences were not statistically significant. CONCLUSIONS: This paper
      outlines a framework for the integration of computational models into virtual
      patients. The opportunities and challenges of model exploitation are discussed
      from a number of user perspectives, considering different levels of model
      integration. The long-term aim for future research is to isolate the most crucial
      factors in the framework and to determine their influence on the integration
      outcome.

PMID- 24463467
TI  - Hard X-ray-induced optical luminescence via biomolecule-directed metal clusters.
AB  - Here, we demonstrate that biomolecule-directed metal clusters are applicable in
      the study of hard X-ray excited optical luminescence, promising a new direction
      in the development of novel X-ray-activated imaging probes. 

PMID- 24463468
TI  - Gene expression of pro- and anti-apoptotic proteins in rock bream (Oplegnathus
      fasciatus) infected with megalocytivirus (family Iridoviridae).
AB  - Viruses belonging to the genus Megalocytivirus cause diseases in marine fishes
      primarily in East and Southeast Asian countries. Rock bream iridovirus (RBIV),
      which is a member of the Megalocytivirus genus, causes severe mass mortalities in
      rock beam (Oplegnathus fasciatus) in Korea. In this study, we assessed apoptosis
      related gene expression patterns in Megalocytivirus-infected rock bream in high
      mortality and low mortality conditions to determine important apoptosis-related
      factors, which may affect fish survival/or death. In the high mortality group
      (100% mortality at 15 dpi), significantly high levels of perforin, granzyme, Fas
      ligand and caspase 9 expression (5.6-, 10.2-, 13.4- and 4.2-fold, respectively)
      were observed in the kidney at 8 dpi. Basal expression levels of Fas and caspase
      3 were observed at 8 d (1.5-/0.7-fold) and 10 dpi (1.3-/0.6-fold), accompanied by
      heavy viral loads (8.12 * 10(6)-2.21 * 10(7)/MUl). Inhibitor of apoptosis 1
      (IAP1) was highly expressed (3.5- to 4.8-fold) at 1 d and 4 dpi; however, IAP1
      was reduced when fish died at 8 d and 10 dpi (1.7- to 2.0-fold), which was not
      significantly different from that of the control group. A similar expression
      pattern was observed in the low mortality group (18% expected mortality at 30
      dpi), which was characterised by a delayed lower magnitude of expression with
      lower viral loads than the high mortality group. Perforin, granzyme and Fas
      ligand expression was significantly higher in the low mortality group than in the
      control group at several sampling points until 30 dpi. Fas and caspases 8, 9 and
      3 expression levels showed no statistical significance until 30 dpi. In the low
      mortality group, significantly higher IAP1 expression compared with the control
      was observed at 10 d (2.2-fold), 20 d (3.6-fold) and 22 dpi (2.0-fold). In
      summary, perforin- and granzyme-related apoptosis initiation signals were
      activated; however, the Fas-induced apoptosis pathway did not efficiently
      respond. Upregulated IAP1 in RBIV-infected rock bream, which was reported for the
      first time in this study, exhibited inhibited apoptotic responses in RBIV
      infected fish. Although it remains unclear whether apoptosis inhibition aids or
      impedes fish survival, our data clearly show that the apoptotic response is
      inhibited in RBIV-infected rock bream. 

PMID- 24463470
TI  - Colocalization of BCL2-positive and -negative follicular lymphoma.

PMID- 24463469
TI  - The relationship of JAK2(V617F) and acquired UPD at chromosome 9p in polycythemia
      vera.

PMID- 24463471
TI  - Quantitative assessments of indoor air pollution and the risk of childhood acute
      leukemia in Shanghai.
AB  - We investigated the association between indoor air pollutants and childhood acute
      leukemia (AL). A total of 105 newly diagnosed cases and 105 1:1 gender-, age-,
      and hospital-matched controls were included. Measurements of indoor pollutants
      (including nitrogen dioxide (NO2) and 17 types of volatile organic compounds
      (VOCs)) were taken with diffusive samplers for 64 pairs of cases and controls.
      Higher concentrations of NO2 and almost half of VOCs were observed in the cases
      than in the controls and were associated with the increased risk of childhood AL.
      The use of synthetic materials for wall decoration and furniture in bedroom was
      related to the risk of childhood AL. Renovating the house in the last 5 years,
      changing furniture in the last 5 years, closing the doors and windows overnight
      in the winter and/or summer, paternal smoking history and outdoor pollutants
      affected VOC concentrations. Our results support the association between
      childhood AL and indoor air pollution. 

PMID- 24463472
TI  - Interrogating trees for isotopic archives of atmospheric sulphur deposition and
      comparison to speleothem records.
AB  - Palaeorecords which depict changes in sulphur dynamics form an invaluable
      resource for recording atmospheric pollution. Tree rings constitute an archive
      that are ubiquitously available and can be absolutely dated, providing the
      potential to explore local- to regional-scale trends in sulphur availability.
      Rapid isotopic analysis by a novel "on-line" method using elemental analyser
      isotope ratio mass spectrometry (EA-IRMS) is developed, achieving sample
      precision of <0.40/00 using sample sizes of 40 mg wood powder. Tree cores from NE
      Italy show trends in pollution, evidenced through increasing concentrations of
      sulphur towards the youngest growth, and inverse trends in sulphur isotopes
      differentiating modern growth with light sulphur isotopes (+0.70/00) from pre
      industrial growth (+7.50/00) influenced by bedrock composition. Comparison with
      speleothem records from the same location demonstrate replication, albeit offset
      in isotopic value due to groundwater storage. Using EA-IRMS, tree ring archives
      form a valuable resource for understanding local- to regional-scale sulphur
      pollution dynamics. 

PMID- 24463473
TI  - Hazard and risk of herbicides for marine microalgae.
AB  - Due to their specific effect on photosynthesis, herbicides pose a potential
      threat to coastal and estuarine microalgae. However, comprehensive understanding
      of the hazard and risk of these contaminants is currently lacking. Therefore the
      aim of the present study was to investigate the toxic effects of four ubiquitous
      herbicides (atrazine, diuron, Irgarol((r))1051 and isoproturon) and herbicide
      mixtures on marine microalgae. Using a Pulse Amplitude Modulation (PAM)
      fluorometry based bioassay we demonstrated a clear species and herbicide specific
      toxicity and showed that the current environmental legislation does not protect
      algae sufficiently against diuron and isoproturon. Although a low actual risk of
      herbicides in the field was demonstrated, monitoring data revealed that
      concentrations occasionally reach potential effect levels. Hence it cannot be
      excluded that herbicides contribute to observed changes in phytoplankton species
      composition in coastal waters, but this is likely to occur only occasionally. 

PMID- 24463474
TI  - Soil removal as a decontamination practice and radiocesium accumulation in
      tadpoles in rice paddies at Fukushima.
AB  - We investigated the biological accumulation of radiocesium in tadpoles [Rana
      (Pelophylax) porosa porosa] in rice paddies with and without decontamination
      practice at Fukushima. Radiocesium was accumulated in surface part of soils both
      in the control and decontaminated paddies one year after decontamination. Mean
      (134)Cs and (137)Cs concentrations in tadpoles in the control and decontaminated
      paddies were 3000 and 4500, and 600 and 890 Bq/kg dry weight, respectively.
      Radiocesium concentrations in surface soil (0-5 cm depth) and tadpoles in the
      decontaminated paddy were five times smaller than in the control paddy. These
      results suggest that decontamination practice can reduce radiocesium
      concentrations in both soil and tadpoles. However, at the decontaminated paddy,
      radiocesium concentrations in surface soils became 3.8 times greater one year
      after decontamination, which indicates that monitoring the subsequent movement of
      radiocesium in rice paddies and surrounding areas is essential for examining
      contamination propagation. 

PMID- 24463475
TI  - MRI compatible Nb-Ta-Zr alloys used for vascular stents: optimization for
      mechanical properties.
AB  - With the increased usage of magnetic resonance imaging (MRI) as a diagnostic tool
      in clinic, the currently-used metals for vascular stents, such as 316L stainless
      steel (SS), Co-Cr alloys and Ni-Ti alloys, are challenged by their unsatisfactory
      MRI compatibility, due to their constituents containing ferromagnetic elements.
      To provide more MRI compatible vascular stents, the Nb-xTa-2Zr (30<=x<=70) series
      alloys were selected in the current work. Several key properties of these alloys
      were optimized in terms of stent requirements, including magnetic susceptibility,
      elastic modulus and tensile properties. In the as-cast state, a single-phase
      solid solution with bcc structure was formed in the alloys. The volume magnetic
      susceptibility (chiv) and Young's modulus (E) of the alloys scaled linearly with
      the Ta content. Increasing the Ta content gave rise to the decreased chiv and the
      increased E, together with the elevated yield strength but less-changed
      elongation. From multiple requirements for the stents, the Nb-60Ta-2Zr alloy
      exhibits an optimal properties, including the chiv of about 3% of the 316L SS,
      the E of 142GPa superior to pure niobium, high mass density of 12.03g/cm(3)
      favored to the X-ray visibility, yield strength of ~330MPa comparable to the 316L
      SS and a elongation of ~24%. These remarkable advantages make it quite promising
      as a new candidate of stent metals. 

PMID- 24463476
TI  - Effects of different blasting materials on charge generation and decay on
      titanium surface after sandblasting.
AB  - It has been reported that sandblasting titanium with alumina (Al2O3) powder could
      generate a negative electric charge on titanium surface. This has been proven to
      promote osteoblast activities and possibly osseointegration. The purpose of this
      pilot study was to investigate the effects of different blasting materials, in
      terms of the grit sizes and electro-negativity, on the generation of a negative
      charge on the titanium surface. The aim was also to make use of these results to
      deduct the underlying mechanism of charge generation by sandblasting. Together 60
      c.p. 2 titanium plates were machine-cut and polished for sandblasting, and
      divided into 6 groups with 10 plates in each. Every plate in the study groups was
      sandblasted with one of the following 6 powder materials: 110um Al2O3 grits, 50um
      Al2O3 grits, 150-300um glass beads, 45-75um glass beads, 250um Al powder and 44um
      Al powder. The static voltage on the surface of every titanium plate was measured
      immediately after sandblasting. The static voltages of the titanium plates were
      recorded and processed using statistical analysis. The results suggested that
      only sandblasting with 45-75um glass beads generated a positive charge on
      titanium, while using all other blasting materials lead to a negative charge.
      Furthermore, blasting grits of the same powder material but of different sizes
      might lead to different amount and polarity of the charges. This triboelectric
      effect is likely to be the main mechanism for charge generation through
      sandblasting. 

PMID- 24463477
TI  - The biomechanical behaviour of the bridging vein-superior sagittal sinus complex
      with implications for the mechanopathology of acute subdural haematoma.
AB  - BACKGROUND: Traumatic brain injury is expected to become the major cause of death
      and disability for children and young adults by the year 2020. One of the most
      frequent and most morbid pathologies resulted from a head trauma is acute
      subdural haematoma (ASDH). For nearly one third of the ASDH cases the
      etiopathology directly relates to a bridging vein (BV) rupture. METHODS: In the
      current study the bridging vein-superior sagittal sinus (BV-SSS) units were
      axially stretched until failure for strain rates ranging from 2.66s(-1) to
      185.61s(-1), in order to investigate any strain rate dependency in their
      mechanical behaviour. FINDINGS: Results showed that up to 200s(-1), the effect of
      the strain rate on veins' mechanical behaviour is outweighed by the large
      morphological intra- and inter-individual variations. Gender had a strong
      influence on the BVs geometrical description, but exerted no direct influence on
      the BV biomechanical parameters. Veins' dimensions had the strongest influence on
      the BV mechanical behaviour and on the failure mechanism. INTERPRETATION: The
      present study brings important contribution to the ASDH research, emphasising the
      importance of considering the BV-SSS complex as a whole when trying to describe
      the ASDH mechanopathology.

PMID- 24463478
TI  - Effect of dexmedetomidine combined with sufentanil for post-caesarean section
      intravenous analgesia: a randomised, placebo-controlled study.
AB  - BACKGROUND: Few studies have investigated the use of dexmedetomidine in obstetric
      anaesthesia. OBJECTIVE: To evaluate the effect of dexmedetomidine combined with
      sufentanil for patient-controlled analgesia (PCA) after caesarean section under
      spinal anaesthesia. DESIGN: An interventional, randomised, double-blinded,
      placebo-controlled clinical study. SETTING: Department of Anaesthesiology,
      Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
      PATIENTS: One hundred and twenty parturients (American Society of
      Anesthesiologists class 1 or 2) scheduled for elective caesarean delivery under
      spinal anaesthesia randomly allocated into three groups (n = 40 each).
      INTERVENTIONS: Group 1: physiological saline bolus after delivery and sufentanil
      PCA, Group 2: dexmedetomidine bolus (0.5 MUg kg) after delivery and sufentanil
      PCA, Group 3: dexmedetomidine bolus (0.5 MUg kg) after delivery and sufentanil
      with dexmedetomidine PCA (background infusion of 0.045 MUg kg h with a bolus of
      0.07 MUg kg). MAIN OUTCOME MEASURES: The total consumption of sufentanil. Pain
      scores at rest evaluated with a visual analogue scale (VAS) and Ramsay sedation
      score (RSS) were recorded at the 4, 8 and 24 h after surgery. The patients' pain
      threshold (PTh) and pain tolerance threshold (PTTh) were measured before surgery
      and 1 h after initial study drug administration. Satisfaction scores were
      collected 24 h after surgery. RESULTS: Sufentanil consumption in group 3 was 43.9
      +/- 19.2 MUg, significantly lower than in group 1 (54.5 +/- 23.9 MUg) and group 2
      (56.3 +/- 20.6 MUg) (P < 0.05). Compared with group 3, VAS was increased at 4, 8
      and 24 h after surgery in groups 1 and 2 (P < 0.05); there was no difference
      between groups 1 and 2. PTh and PTTh were significantly increased 1 h after drug
      administration in groups 2 (1.59 +/- 0.45, 2.57 +/- 0.46 mA) and 3 (1.74 +/-
      0.37, 2.56 +/- 0.48 mA) compared with group 1 (1.49 +/- 0.49, 2.42 +/- 0.62 mA)
      (P < 0.05). CONCLUSION: The combination of sufentanil and dexmedetomidine for PCA
      after caesarean section can reduce sufentanil consumption and improve
      parturients' satisfaction compared with sufentanil PCA alone. TRIAL REGISTRATION:
      ChiCTR-TRC-11001442.

PMID- 24463479
TI  - Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia.
AB  - BACKGROUND: Friedreich ataxia (FRDA) is a neurodegenerative disease caused by
      mutations in the frataxin (FXN) gene, resulting in reduced expression of the
      mitochondrial protein frataxin. Improved understanding of the pathophysiology of
      the disease has led to a growing need for informative biomarkers to assess
      disease progression and response to therapeutic intervention. OBJECTIVE: To
      evaluate the performance of frataxin measurements as a diagnostic tool using two
      different immunoassays. METHODS: Clinical and demographic information was
      provided through an ongoing longitudinal natural history study on FRDA. Frataxin
      protein levels from multiple cell types in controls, carriers and FRDA patients
      were measured and compared using a lateral flow immunoassay and a Luminex xMAP
      based immunoassay. Receiver operating characteristic curve analyses were then
      performed to evaluate the sensitivity, specificity, and positive and negative
      predictive values for each immunoassay. RESULTS: For whole blood and buccal
      cells, analysing FRDA patients and carriers together in a cohort resulted in
      higher sensitivities and positive predictive values compared with analyzing
      controls and carriers together, with similar results between each tissue type. We
      then compared the usefulness of a lateral flow immunoassay with a multianalyte
      Luminex xMAP-based immunoassay, and showed that both assays demonstrate high
      positive predictive values with low rates of false negatives and false positives.
      CONCLUSIONS: Frataxin measurements from peripheral tissues can be used to
      identify FRDA patients and carriers. While multiple cell types and assays may be
      useful for diagnostic purposes, each assay and cell type used has its advantages
      and disadvantages depending on study design and scope.

PMID- 24463480
TI  - Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical
      trials.
AB  - OBJECTIVES: The use of clinical staging in the fatal neurodegenerative disease
      amyotrophic lateral sclerosis would have value in optimising future therapeutic
      trials. We aimed to use previous clinical trial data to determine the length of
      time patients spend in each of four proposed stages, its range and transition
      patterns to subsequent stages. METHODS: Using databases from two multicentre
      clinical trials, patients were retrospectively staged through the trial course.
      At each stage we assessed whether patients then progressed to an earlier,
      consecutive or later stage or death. Duration spent in each stage before
      progression to a later stage was calculated. RESULTS: There were 725 patients. No
      patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed
      to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage
      1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3,
      42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients
      progressed to death. Transition times between stages had a median duration of 3
      to 7 months for stages 2 to 4. DISCUSSION: We have shown using trial data that
      transition times between stages are short. Use of stage duration as an endpoint
      might allow a shorter trial duration. We have shown face validity in this system
      as most patients progress through consecutive stages, and none revert to earlier
      stages. Furthermore, we have shown the system is reliable across populations and
      therefore has content validity.

PMID- 24463481
TI  - Basilar extension and posterior inferior cerebellar artery involvement as risk
      factors for progression of the unruptured spontaneous intradural vertebral artery
      dissection.
AB  - BACKGROUND AND PURPOSE: Spontaneous intradural vertebral artery dissection
      (siVAD) primarily causes stroke in young and middle-aged individuals; however,
      data on the relationship between vertebrobasilar morphology and the progression
      of siVAD are limited. METHODS: We retrospectively reviewed the data of 77 adult
      patients who were diagnosed with unruptured siVAD and treated conservatively. We
      analysed the clinical characteristics, vertebrobasilar morphologies and
      progression. Progression was defined as siVAD-induced stroke or morphological
      worsening of the siVAD. RESULTS: Twenty patients experienced progression.
      Recurrent ischaemic events that occurred in the vertebrobasilar territory were
      seen in three patients (3.9%). Two of these three patients and other 17 patients
      showed morphological worsening. None of the patients presented with subarachnoid
      haemorrhage. The log-rank test showed male sex, migraine, basilar extension and
      the posterior inferior cerebellar artery involvement were associated with the
      progression. Multivariate analysis using the Cox proportional hazards model
      showed that only basilar extension and the posterior inferior cerebellar artery
      involvement were significantly related to the progression (p=0.012 and 0.019). In
      addition, patients with these two vertebrobasilar morphologies had a
      significantly shorter period of progression of siVAD than those without these
      morphologies (both, median 242 days; one of two, median 1292 days; none, median
      2445 days). CONCLUSIONS: Thus, some vertebrobasilar morphologies might be markers
      of the progression of unruptured siVAD. Although all unruptured siVAD patients
      should be closely monitored, those with basilar extension and posterior inferior
      cerebellar artery involvement should perhaps be more carefully followed than
      those without such morphologies.

PMID- 24463482
TI  - Taxanes, past, present, and future impact on non-small cell lung cancer.
AB  - Taxanes are novel microtubule-stabilizing agents and have shown efficacy in non
      small cell lung cancer (NSCLC) since the 1990s. Paclitaxel and docetaxel have
      been used either as single agents or in combination with a platinum compound. The
      newer generation albumin-bound taxane, nab-paclitaxel, has also shown similar
      efficacy in advanced NSCLC, both as a single agent and in combination with a
      platinum compound. Nab-paclitaxel, being Cremophor EL free, appears to have a
      better toxicity profile than paclitaxel. Taxane/platinum combinations still
      remain the foundation of treatment for advanced or metastatic NSCLC. Docetaxel
      and paclitaxel as single agents have also shown efficacy in the second-line
      setting in advanced/metastatic NSCLC. Oral formulations of paclitaxel and
      docetaxel are of great interest, but have yet to receive regulatory approval in
      this disease. The phase I-II trials have shown that these formulations are
      feasible in the clinical setting. 

PMID- 24463483
TI  - EAPB0503, a novel imidazoquinoxaline derivative, inhibits growth and induces
      apoptosis in chronic myeloid leukemia cells.
AB  - Imatinib, the first-generation tyrosine kinase inhibitor, revolutionized the
      therapeutic management of chronic myeloid leukemia (CML) and is highly effective
      in inducing remissions and prolonging the survival of CML patients. However, one
      third of patients develop intolerance or resistance to treatment, and CML stem
      cells remain insensitive to this therapy, leading almost inevitably to relapse
      upon treatment discontinuation. Imidazoquinoxalines are imiquimod derivatives
      that induce growth inhibition and induction of caspase-dependent apoptosis in
      melanoma and T-cell lymphoma cells. We investigated the effects of EAPB0203 and
      EAPB0503, two novel imidazoquinoxaline derivatives, on human CML cell lines and
      showed that they induced a dose-dependent and time-dependent cell growth
      inhibition. EAPB0503 proved more potent and induced a specific cell cycle arrest
      in mitosis in CML cells and direct activation of apoptosis as evidenced by
      increased pre-G0 population, breakdown of mitochondrial membrane potential, PARP
      cleavage, and DNA breakage. Interestingly, EAPB0503 decreased BCR-ABL oncoprotein
      levels. The combination of EAPB0503 with imatinib synergized to inhibit the
      proliferation of CML cells, and most importantly, EABP0503 inhibited the
      proliferation of imatinib-resistant CML cells, offering promising therapeutic
      modalities that would circumvent resistance to tyrosine kinase inhibitors and
      improve the prognosis of CML. 

PMID- 24463484
TI  - Taxanes: impact on pancreatic cancer.
AB  - Taxanes are core therapeutic components for several advanced malignancies, and
      have been studied extensively in pancreatic adenocarcinomas with mixed results.
      Although the triplet combination FOLFIRINOX improves outcomes for patients with
      metastatic disease, it is compounded by significant toxicity, and novel regimens,
      rationally designed and based on thorough mechanistic activity on the tumor
      targets, are clearly needed. Solvent-based taxanes, docetaxel and paclitaxel,
      have little activity as single agents, but combinations with fluoropyrimidines
      and gemcitabine show efficacy, albeit they have not undergone testing in phase
      III trials. Pancreatic cancer is characterized by an abundant desmoplastic,
      fibroinflammatory and hypoperfused stroma, which has been blamed for its overall
      chemoresistance. Nanoparticle bound paclitaxel (nab-paclitaxel) has been
      pharmacologically designed as a novel water-soluble agent, with improved
      therapeutic index compared with the cremophor-based formulation, capable of
      achieving higher systemic exposure. In preclinical systems, when combined with
      gemcitabine, nab-paclitaxel increased intratumoral gemcitabine delivery, possibly
      due to inducing stromal 'collapse' and through inhibition of the gemcitabine
      catabolizing enzyme cytidine deaminase. Most recently, the combination of nab
      paclitaxel and gemcitabine demonstrated significant survival benefit with good
      tolerability in metastatic pancreatic cancer in the phase III trial MPACT, and
      now represents one of the gold-standard regimens for this disease. Although
      taxanes are overall potent chemotherapeutics for various cancers, it is clear
      that for meaningful results in pancreatic adenocarcinomas, rationally designed
      combinations and novel technologies for drug delivery are likely to be most
      successful. 

PMID- 24463485
TI  - Binding and activation of small molecules by a quintuply bonded chromium dimer.
AB  - The quintuply bonded [(H)L(iPr)Cr]2 reacts with various small molecules,
      revealing a pattern of two kinds of transformations. Unsaturated molecules that
      are neither polar nor oxidizing form binuclear [2+n] cycloaddition products
      retaining Cr-Cr quadruple bonds. In contrast, polar or oxidizing molecules effect
      the complete cleavage of the Cr-Cr bond. 

PMID- 24463486
TI  - Multi-generation overgrowth induced synthesis of three-dimensional highly
      branched palladium tetrapods and their electrocatalytic activity for formic acid
      oxidation.
AB  - Highly branched noble metal nanostructures are highly attractive for catalytic
      applications owing to their specific physical and chemical properties. In this
      work, three-dimensional highly branched palladium tetrapods (Pd-THBTs) have been
      constructed in the presence of polyvinylpyrrolidone (PVP) through one-step
      hydrothermal reduction of ethylenediamine-tetramethylene phosphonate
      palladium(II) (EDTMP-Pd(II)) by formaldehyde. The morphology and structure of the
      Pd-THBTs were fully characterized and the growth mechanism was explored and
      discussed based on the experimental observation. The concave Pd tetrahedra grew
      into highly branched Pd tetrapods consisting of four nanothorn-like branches with
      tetrahedral dimensions through interesting multi-generation nanocrystal
      overgrowth. The electrocatalytic activities of the as-synthesized Pd-THBTs toward
      formic acid oxidation were also studied by cyclic voltammetry and
      chronoamperometry. The Pd-THBTs showed higher catalytic activity and stability
      for formic acid oxidation than the commercial Pd black.

PMID- 24463487
TI  - Prediction of fat-free body mass from bioelectrical impedance and anthropometry
      among 3-year-old children using DXA.
AB  - For 3-year-old children suitable methods to estimate body composition are sparse.
      We aimed to develop predictive equations for estimating fat-free mass (FFM) from
      bioelectrical impedance (BIA) and anthropometry using dual-energy X-ray
      absorptiometry (DXA) as reference method using data from 99 healthy 3-year-old
      Danish children. Predictive equations were derived from two multiple linear
      regression models, a comprehensive model (height(2)/resistance (RI), six
      anthropometric measurements) and a simple model (RI, height, weight). Their
      uncertainty was quantified by means of 10-fold cross-validation approach.
      Prediction error of FFM was 3.0% for both equations (root mean square error: 360
      and 356 g, respectively). The derived equations produced BIA-based prediction of
      FFM and FM near DXA scan results. We suggest that the predictive equations can be
      applied in similar population samples aged 2-4 years. The derived equations may
      prove useful for studies linking body composition to early risk factors and early
      onset of obesity.

PMID- 24463488
TI  - The energy transfer and effect of doped Mg2+ in Ca3Sc2Si3O12:Ce3+, Pr3+ phosphor
      for white LEDs.
AB  - The energy transfer and luminescence properties in the Ce(3+) and Pr(3+) co
      activated Ca3Sc2Si3O12 (CSS) silicate garnet are studied in our work. The
      addition of Pr(3+) exhibits a red emission around 610 nm in the green phosphor
      CSS:Ce(3+), but the amount of Pr(3+) incorporated into the phosphor is very
      limited due to the charge mismatch when Pr(3+) substitutes for Ca(2+) in CSS. In
      order to promote Pr(3+) incorporation into CSS lattices to enhance the red
      emission component, the addition of Mg(2+) incorporated into Sc(3+) site is
      performed to compensate the residual positive charge caused by the substitution
      of Pr(3+) for Ca(2+) in CSS. Finally, a white LED with color rendering index of
      80 and correlated color temperature of 8715 K is obtained by combining the single
      CSS:0.05Ce(3+), 0.01Pr(3+), 0.3Mg(2+) phosphor with a blue-emitting InGaN LED
      chip. 

PMID- 24463489
TI  - Therapeutic manipulation of the ductus arteriosus: current options and future
      prospects.
AB  - The ductus arteriosus is a large fetal vessel connecting the pulmonary artery
      with the aorta and allowing right ventricular blood to bypass the unexpanded
      lungs. At birth, with the start of lung ventilation and the attendant rise in
      blood oxygen tension, the ductus closes and the cardiovascular system acquires
      its final arrangement. However, in the prematurely born infant, this shunt may
      remain patent (patent ductus arteriosus--PDA) with adverse consequences on
      hemodynamic homeostasis. Conversely, there are cardiac malformations in which
      patency of the duct is required to maintain the pulmonary or systemic circulation
      prior to corrective surgery. Based on the notion that patency is an active
      process sustained primarily by prostaglandin (PG) E2, PDA is currently managed
      with synthesis inhibitors, indomethacin or ibuprofen, while any necessary
      persistence of the duct after birth is achieved with the infusion of PGE1.
      However, the former procedure presents a relatively high incidence of failures
      for the likely combination of the 2 events: the relaxing influence of the agents
      compensating for the loss of PGE2 and the immaturity of the oxygen-triggered
      contractile mechanism. On the other hand, PGE1 treatment loses some of its
      efficacy with time and may also be complicated by troublesome side effects. This
      article presents possible new approaches to therapy still based on the
      manipulation of the relaxing mechanism(s) responsible for duct patency. At the
      same time, however, the idea is put forward that the management of these sick
      infants may find its definitive solution only with tools being designed on the
      operation of the oxygen-sensing/effector system.

PMID- 24463490
TI  - Reparative effects of neural stem cells in neonatal rats with hypoxic-ischemic
      injury are not influenced by host sex.
AB  - BACKGROUND: Gender is increasingly recognized as an important influence on brain
      development, disease susceptibility, and response to pharmacologic/rehabilitative
      treatments. In regenerative medicine, it remains entirely unknown whether there
      is an interaction between transplanted stem cells and host gender that might bias
      efficacy and safety in some patients but not others. METHODS: We examined the
      role of recipient gender in a neonatal rat hypoxic-ischemic injury (HII) model,
      treated with female human neuronal stem cells (hNSCs), labeled with
      superparamagnetic iron oxide particles implanted into the contralateral cerebral
      ventricle. We monitored HII evolution (by magnetic resonance imaging,
      histopathology, behavioral testing) and hNSC fate (migration, replication,
      viability). RESULTS: Recipient gender after implantation did not influence the
      volume or location of ischemic injury (1, 30, or 90 d) or behavior (90 d).
      Superparamagnetic iron oxide labeling did not influence HII evolution.
      Implantation had its greatest benefit on mild/moderate injuries, which remained
      stable rather than increasing as in severe HII as is the natural history for such
      lesions. CONCLUSION: Our results suggest that hNSC treatment (including using
      hNSCs that are prelabeled with iron to allow tracking in real time by magnetic
      resonance imaging) would be equally safe and effective for male and female human
      newborns with mild-to-moderate HII.

PMID- 24463491
TI  - Extreme temperatures in the adult stage shape delayed effects of larval pesticide
      stress: a comparison between latitudes.
AB  - Global warming and pesticide pollution are major threats for aquatic
      biodiversity. Yet, how pesticide effects are influenced by the increased
      frequency of extreme temperatures under global warming and how local thermal
      adaptation may mitigate these effects is unknown. We therefore investigated the
      combined impact of larval chlorpyrifos exposure, larval food stress and adult
      heat exposure on a set of fitness-related traits in replicated low- and high
      latitude populations of the damselfly Ischnura elegans. Larval pesticide exposure
      resulted in lighter adults with a higher water content, lower fat content, higher
      Hsp70 levels and a lower immune function (PO activity). Heat exposure reduced
      water content, mass, fat content and flying ability. Importantly, both stressors
      interacted across metamorphosis: adult heat exposure lowered the reduction of fat
      content, and generated a stronger decrease in PO activity in pesticide-exposed
      animals. Larval pesticide exposure and larval food stress also reduced the
      defense response to the adult heat stress in terms of increased Hsp70 levels. In
      line with strong life history differences in the unstressed control situation,
      high-latitude animals were less sensitive to food stress (body mass and water
      content), but more sensitive to pesticide stress (development time and PO
      activity) and heat exposure (PO activity and Hsp70 levels). While low-latitude
      adults could better withstand the extreme temperature as suggested by the weaker
      increase in Hsp70, heat exposure similarly affected the delayed effects of larval
      pesticide exposure at both latitudes. Our study highlighted two key findings
      relevant for ecological risk assessment under global warming. Firstly, the
      delayed effects of larval pesticide exposure on adult damselflies depended upon
      subsequent adult heat exposure, indicating that larval pesticide stress and adult
      heat stress interacted across metamorphosis. Secondly, low- and high-latitude
      animals responded differently to the imposed stressors, highlighting that
      intraspecific evolution along natural thermal gradients may shape sensitivity to
      pesticides. 

PMID- 24463492
TI  - Effects of dechlorane plus on the hepatic proteome of juvenile Chinese sturgeon
      (Acipenser sinensis).
AB  - Dechlorane Plus (DP), an alternative to decabromodiphenyl ether (BDE-209), is a
      widely used polychlorinated flame retardant that is frequently detected in
      aquatic ecosystems. While the mechanisms of toxicity of BDE-209 have been well
      documented, less is known about the toxicity of DP. In this study, juvenile
      Chinese sturgeon (Acipenser sinensis) were treated with DP at doses of 1, 10, and
      100mg/kg wet weight for 14 days via a single intraperitoneal injection (i.p.).
      After 14 days, liver proteomes of juvenile Chinese sturgeon were analyzed using
      two-dimensional electrophoresis (2-DE) coupled matrix-assisted laser
      desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS).
      A total of 39 protein spots were significantly altered in abundance (>2-fold) and
      of these proteins, 27 were successfully identified. Proteins related to the
      stress response that included heat shock cognate protein 70 and T-complex protein
      1 were significantly increased and decreased in abundance, respectively.
      Moreover, Ras-related protein Rab-6B and GDP dissociation inhibitor 2, proteins
      that are involved in small G-protein signal cascades, were decreased in abundance
      2- to 5-fold. Annexin A4, which is associated with Ca(2+) signaling pathways, was
      also markedly decreased by 2-fold in the liver. Pathway analysis of
      differentially regulated proteins revealed that DP interfered with metabolism and
      was associated with proteins related to apoptosis and cell differentiation. Based
      upon protein responses, we suggest that DP has effects on the generalized stress
      response, small G-protein signal cascades, Ca(2+) signaling pathway, and
      metabolic process, and may induce apoptosis in the liver. This study offers novel
      mechanistic insight into the protein responses induced in the liver with DP, an
      increasingly used and understudied flame retardant. 

PMID- 24463493
TI  - Sulphate, more than a nutrient, protects the microalga Chlamydomonas moewusii
      from cadmium toxicity.
AB  - Sulphur is an essential macroelement that plays important roles in living
      organisms. The thiol rich sulphur compounds, such as cysteine, gamma-Glu-Cys,
      glutathione and phytochelatins participate in the tolerance mechanisms against
      cadmium toxicity. Plants, algae, yeasts and most prokaryotes cover their demand
      for reduced sulphur by reduction of inorganic sulphate. The aim of this study was
      to investigate, using a bifactorial experimental design, the effect of different
      sulphate concentrations in the nutrient solution on cadmium toxicity in the
      freshwater microalga Chlamydomonas moewusii. Cell growth, kinetic parameters of
      sulphate utilization and intracellular concentrations of low-molecular mass thiol
      compounds were determined. A mathematical model to describe the growth of this
      microalga based on the effects of sulphate and cadmium was obtained. An ANOVA
      revealed an interaction between them, 16% of the effect sizes was explained by
      this interaction. A higher amount of sulphate in the culture medium allowed a
      higher cadmium tolerance due to an increase in the thiol compound biosynthesis.
      The amount of low-molecular mass thiol compounds, mainly phytochelatins,
      synthesized by this microalga was significantly dependent on the sulphate and
      cadmium concentrations; the higher phytochelatin content was obtained in cultures
      with 4 mg Cd/L and 1mM sulphate. The maximum EC50 value (based on nominal cadmium
      concentration) reached for this microalga was 4.46 +/- 0.42 mg Cd/L when the
      sulphate concentration added to the culture medium was also 1mM. An increase in
      the sulphate concentration, in deficient environments, could alleviate the toxic
      effect of this metal; however, a relative excess is also negative. The results
      obtained showed a substrate inhibition for this nutrient. An uncompetitive model
      for sulphate was chosen to establish the mathematical model that links both
      factors.

PMID- 24463494
TI  - Surgically relevant localization of the central sulcus with high-density
      somatosensory-evoked potentials compared with functional magnetic resonance
      imaging.
AB  - BACKGROUND: Resection of abnormal brain tissue lying near the sensorimotor cortex
      entails precise localization of the central sulcus. Mapping of this area is
      achieved by applying invasive direct cortical electrical stimulation. However,
      noninvasive methods, particularly functional magnetic resonance imaging (fMRI),
      are also used. As a supplement to fMRI, localization of somatosensory-evoked
      potentials (SEPs) recorded with an electroencephalogram (EEG) has been proposed,
      but has not found its place in clinical practice. OBJECTIVE: To assess
      localization accuracy of the hand somatosensory cortex with SEP source imaging.
      METHODS: We applied electrical source imaging in 49 subjects, recorded with high
      density EEG (256 channels). We compared it with fMRI in 18 participants and with
      direct cortical electrical stimulation in 6 epileptic patients. RESULTS:
      Comparison of SEP source imaging with fMRI indicated differences of 3 to 8 mm,
      with the exception of the mesial-distal orientation, where variances of up to 20
      mm were found. This discrepancy is explained by the fact that the source maximum
      of the first SEP peak is localized deep in the central sulcus (area 3b), where
      information initially arrives. Conversely, fMRI showed maximal signal change on
      the lateral surface of the postcentral gyrus (area 1), where sensory information
      is integrated later in time. Electrical source imaging and fMRI showed mean
      Euclidean distances of 13 and 14 mm, respectively, from the contacts where
      electrocorticography elicited sensory phenomena of the contralateral upper limb.
      CONCLUSION: SEP source imaging, based on high-density EEG, reliably identifies
      the depth of the central sulcus. Moreover, it is a simple, flexible, and
      relatively inexpensive alternative to fMRI.

PMID- 24463495
TI  - Optogenetic inactivation of the subthalamic nucleus improves forelimb akinesia in
      a rat model of Parkinson disease.
AB  - BACKGROUND: The inhibition of neuronal activity by electrical deep brain
      stimulation is one of the mechanisms explaining the therapeutic effects in
      patients with Parkinson disease (PD) but cannot specifically activate or
      inactivate different types of neurons. Recently, a new technology based on
      optogenetics has been developed to modulate the activity of specific neurons.
      However, the therapeutic effects of optical inactivation in the subthalamic
      nucleus (STN) have not been fully investigated. OBJECTIVE: To perform various
      behavioral tests to evaluate changes in motor functions in a PD rat model after
      optogene expression and, unlike previous studies, to assess the therapeutic
      effects of direct optogenetic inactivation in the STN. METHODS: 6-Hydroxydopamine
      induced hemiparkinsonian rats received injections of hSynapsin1-NpHR-YFP adeno
      associated virus or an equivalent volume of phosphate-buffered saline. Three
      weeks after injection of adeno-associated virus or phosphate-buffered saline, the
      optic fiber was implanted into the ipsilateral STN. A stepping test, a cylinder
      test, and an apomorphine-induced rotation test were performed in 3 sequential
      steps: during light-off state, during light stimulation, and again during light
      off state. RESULTS: Stepping tests revealed that optical inhibition of the STN
      significantly improved 6-hydroxydopamine-induced forelimb akinesia. PD motor
      signs, as assessed by cylinder and apomorphine tests, were not affected by
      optical inhibition. Immunofluorescence revealed that halorhodopsin was highly
      expressed and colocalized with vesicular glutamate transporter 2 in the STN.
      CONCLUSION: Optogenetic inhibition in the STN may be effective in improving
      contralateral forelimb akinesia but not in changing forelimb preference or
      reducing dopaminergic receptor supersensitivity. These findings are useful as a
      basis for future studies on optogenetics in PD.

PMID- 24463496
TI  - Poly (ether sulfone) as a scintillation material for radiation detection.
AB  - Considerable attention has been drawn to the advantages of using aromatic ring
      polymers for scintillation materials in radiation detection. Thus, it is
      important to identify and characterise those with the best potential. Here, we
      characterise poly (ether sulfone) (PES), which is an amber-coloured transparent
      resin that possesses sulfur as a main component and has a density of 1.37
      g/cm(3). PES emits short-wavelength light with a 350-nm maximum. By taking into
      account its emission spectrum, we demonstrate that its effective refractive index
      is 1.74. Light yield distributions generated by (137)Cs and (207)Bi radioactive
      sources were obtained. PES has a light yield that is 2.21 times that of poly
      (ethylene terephthalate), and 0.31 times that of poly (ethylene naphthalate). The
      energy response to 5,486 keV alpha particles emitted from (241)Am was 546 +/- 81
      keV electron equivalents (keVee), while the energy resolution was 17.0 +/- 0.1%.
      The energy response to 6,118 keV alpha particles emitted from (252)Cf was 598 +/-
      83 keVee, while the energy resolution was 16.0 +/- 0.1%. Overall, PES has
      potential for use as a scintillation material in radiation detection.

PMID- 24463497
TI  - Generation of male germ cells from mouse induced pluripotent stem cells in vitro.
AB  - Germ cells are the only cell type that passes genetic information to the next
      generation. In most metazoan species, primordial germ cells (PGCs) were induced
      from epiblasts by signals from the neighboring tissues. In vitro derivation of
      germ cells from the pluripotent stem cells (PSCs) such as embryonic stem cells
      (ESCs) and induced PSCs (iPSCs) are of great values for the treatment of
      infertility, for animal breeding, and for studying the mechanism of germ cell
      development. Although the derivations of male germ cells from PSCs have been
      previously reported, most of the studies failed to conduct the induction in a
      well-controlled and highly efficient manner. Here, we report the derivation of
      induced PGC-like cells (iPGCLCs) from mouse iPSCs via induced epiblast-like cells
      (iEpiLCs) as being monitored by the expression of enhanced green fluorescent
      protein gene under the control of the promoter of stimulated by retinoic acid 8
      (Stra8-EGFP). The identity of iPGCLCs was characterized by examining the
      expression of multiple marker genes as well as by the recovery of spermatogenesis
      after they were transplanted to the testis of infertile W/W(v) mice. Furthermore,
      iPGCLCs were either induced to germline stem cell-like cells (iGSCLCs) or
      reverted back to embryonic germ cell-like cells (iEGCLCs). In conclusion, we have
      established an efficient procedure for inducing iPSCs into iPGCLCs that can be
      further expanded and induced to more developed germ cells. This work indicates
      that the technology of in vitro germ cell induction is becoming more
      sophisticated and can be further improved. 

PMID- 24463498
TI  - Neural stem cells derived from epiblast stem cells display distinctive
      properties.
AB  - Pluripotent stem cells can be derived from preimplantation and postimplantation
      mouse embryos. Embryonic stem cells (ESCs) derived from blastocysts are in a
      "naive" pluripotent state and meet all of the criteria for pluripotency,
      including the ability to generate live pups through tetraploid complementation.
      Epiblast stem cells (EpiSCs) derived from postimplantation epiblasts are in a
      "primed" pluripotent state. ESCs and EpiSCs show different phenotypes and gene
      expression patterns, and EpiSCs are thought to be less pluripotent than ESCs. In
      this study, we addressed whether EpiSCs can be differentiated into specialized
      cell types in vitro. To do this, we first derived EpiSCs from E5.5-6.5 mouse
      embryos containing the Oct4-GFP transgene. We found that EpiSCs expressed
      pluripotency markers and differentiated into all three germ layers in intro and
      in vivo. Interestingly, EpiSCs also efficiently differentiated into a homogenous
      population of neural stem cells (NSCs) in vitro. The EpiSC-derived NSCs (EpiSC
      NSCs) expressed NSC markers (Nestin, Sox2, and Musashi), self-renewed for more
      than 20 passages, and differentiated into neuronal and glial neural cell subtypes
      in vitro. We then transplanted the EpiSC-NSCs into the neonatal mouse brains, and
      found that they were able to survive and differentiate into robust neurons and
      glial cells in the mouse brains, demonstrating that primed pluripotent EpiSCs
      efficiently form functional NSCs. We compared the global gene expression patterns
      of NSCs differentiated from EpiSC-NSCs, ESCs, and brain tissue and found that the
      expression patterns of most genes, including pluripotency and NSC specificity,
      were similarly clustered, but that the developmental process-related genes were
      distantly clustered. Moreover, the global gene expression pattern of brain
      derived NSCs was more similar to that of ESC-derived NSCs than that of EpiSC
      derived NSCs. Taken together, these results indicate that although NSCs,
      regardless of their origins, display very similar in vitro and in vivo
      differentiation properties, their global gene expression profiles may differ,
      depending on the pluripotency state, i.e., naive or primed. 

PMID- 24463499
TI  - [Genetic architecture of chronic inflammatory diseases].

PMID- 24463500
TI  - [Ciclosporin or infliximab for severe steroid refractory ulcerative colitis:
      GETAID study (Group d'Etudes Therapeutiques des Affections Inflammatoires
      Digestives)].

PMID- 24463501
TI  - Evolution of hantaviruses: co-speciation with reservoir hosts for more than 100
      MYR.
AB  - The most recent (9th) Report of the International Committee on Taxonomy of
      Viruses (ICTV) lists 23 established and 30 provisional species in the genus
      Hantavirus (family Bunyaviridae) (Plyusnin et al., 2012). These virus species are
      harbored by altogether 51 species of rodents, shrews and moles and thus in most
      cases it is a relationship of "one hantavirus-one host". Such a tight bond
      between the two, in combination with the observed association between whole
      groups of hantaviruses and (sub)families of rodents, helped to develop the widely
      accepted view of a long-term co-evolution (co-speciation) of these viruses with
      their hosts. Accumulating evidence of host-switching events, both recent and
      ancient, however challenged some of the earlier views on hantavirus evolution. In
      this paper we discuss the concept of hantavirus-host co-speciation and propose a
      scenario of hantavirus evolution based on the currently available genetic
      information. This scenario is based on the hypothesis that hantaviruses are very
      ancient viruses which already existed at the estimated diversification point of
      major placental clades, of which one includes the ancestors of the order Rodentia
      and another the ancestors of both orders Eulipotyphla and Chiroptera; the
      diversification occurred approximately at 90-100 MYA. We also speculate that the
      evolutionary history of hantaviruses extents even deeper in the past, beyond this
      time-point, and included the transmission of a (pre)bunyavirus from an insect
      host to a mammal host.

PMID- 24463502
TI  - Interaction study of rice stripe virus proteins reveals a region of the
      nucleocapsid protein (NP) required for NP self-interaction and nuclear
      localization.
AB  - Rice stripe virus (RSV), which belongs to the genus Tenuivirus, is an emergent
      virus problem. The RSV genome is composed of four single-strand RNAs (RNA1-RNA4)
      and encodes seven proteins. We investigated interactions between six of the RSV
      proteins by yeast-two hybrid (Y2H) assay in vitro and by bimolecular fluorescence
      complementation (BiFC) in planta. Y2H identified self-interaction of the
      nucleocapsid protein (NP) and NS3, while BiFC revealed self-interaction of NP,
      NS3, and NCP. To identify regions(s) and/or crucial amino acid (aa) residues
      required for NP self-interaction, we generated various truncated and aa
      substitution mutants. Y2H assay showed that the N-terminal region of NP (aa 1-56)
      is necessary for NP self-interaction. Further analysis with substitution mutants
      demonstrated that additional aa residues located at 42-47 affected their
      interaction with full-length NP. These results indicate that the N-terminal
      region (aa 1-36 and 42-47) is required for NP self-interaction. BiFC and co
      localization studies showed that the region required for NP self-interaction is
      also required for NP localization at the nucleus. Overall, our results indicate
      that the N-terminal region (aa 1-47) of the NP is important for NP self
      interaction and that six aa residues (42-47) are essential for both NP self
      interaction and nuclear localization. 

PMID- 24463503
TI  - Antitumor activities of an oncolytic adenovirus equipped with a double siRNA
      targeting Ki67 and hTERT in renal cancer cells.
AB  - RNA interference has been proven to be a powerful tool for gene knockdown. Our
      previous study demonstrated that a Ki67 shRNA carried by an adenovirus reduced
      Ki67 expression. In this study, we constructed novel oncolytic adenoviruses in
      which the Ki67 core promoter drove expression of the E1A gene. These adenoviruses
      were equipped with either a Ki67 small interfering RNA (siRNA), a human
      telomerase reverse transcriptase (hTERT) siRNA or a double siRNA targeting Ki67
      and hTERT. We identified the antitumor activities of oncolytic adenoviruses in 3
      renal cancer cell lines, human normal renal tube cell HK-2 and also in nude mice
      bearing KETR-3-xenografted tumors. Our results showed that these oncolytic
      adenoviruses, especially Ki67-ZXC2-double siRNA, could effectively induce
      silencing of the Ki67 and hTERT genes, allow efficient viral replication and
      induce significant apoptosis of renal cancer cells in vitro and in nude mice. We
      concluded that a dual siRNA mediated by oncolytic virotherapy could be an
      effective strategy for cancer gene therapy. 

PMID- 24463504
TI  - Conditioned pain modulation in women with irritable bowel syndrome.
AB  - Evidence suggests that patients with irritable bowel syndrome (IBS) are more
      vigilant to pain-associated stimuli. The aims of this study were to compare women
      with IBS (n = 20) to healthy control (HC, n = 20) women on pain sensitivity,
      conditioned pain modulation (CPM) efficiency, and salivary cortisol levels before
      and after the CPM test and to examine the relationship of CPM efficiency with
      gastrointestinal pain, somatic pain, psychological distress symptoms, and
      salivary cortisol levels in each group. Women, aged 20-42 years, gave consent,
      completed questionnaires, and kept a symptom diary for 2 weeks. CPM efficiency
      was tested with a heat test stimulus and cold water condition stimulus in a
      laboratory between 8 and 10 a.m. on a follicular phase day. Salivary cortisol
      samples were collected just before and after the experimental testing. Compared
      to the HC group, women with IBS reported more days with gastrointestinal and
      somatic pain/discomfort, psychological distress, fatigue, and feeling stressed.
      During the CPM baseline testing, women with IBS reported greater pain sensitivity
      compared to the HC group. There was no significant group difference in salivary
      cortisol levels nor in CPM efficiency, though a post-hoc analysis showed a higher
      prevalence of impaired CPM efficiency among IBS subjects with more severe lower
      GI symptoms. In the IBS group, reduced CPM efficiency was associated with daily
      abdominal pain/discomfort and psychological distress. Overall, women with IBS
      exhibited an increased sensitivity to thermal stimuli. Impaired CPM was present
      in a subset of women with IBS. 

PMID- 24463505
TI  - Evolutionary biology: Brotherly love benefits females.

PMID- 24463506
TI  - Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical
      sulphur cycle.
AB  - Sulphoquinovose (SQ, 6-deoxy-6-sulphoglucose) has been known for 50 years as the
      polar headgroup of the plant sulpholipid in the photosynthetic membranes of all
      higher plants, mosses, ferns, algae and most photosynthetic bacteria. It is also
      found in some non-photosynthetic bacteria, and SQ is part of the surface layer of
      some Archaea. The estimated annual production of SQ is 10,000,000,000 tonnes (10
      petagrams), thus it comprises a major portion of the organo-sulphur in nature,
      where SQ is degraded by bacteria. However, despite evidence for at least three
      different degradative pathways in bacteria, no enzymic reaction or gene in any
      pathway has been defined, although a sulphoglycolytic pathway has been proposed.
      Here we show that Escherichia coli K-12, the most widely studied prokaryotic
      model organism, performs sulphoglycolysis, in addition to standard glycolysis. SQ
      is catabolised through four newly discovered reactions that we established using
      purified, heterologously expressed enzymes: SQ isomerase, 6-deoxy-6
      sulphofructose (SF) kinase, 6-deoxy-6-sulphofructose-1-phosphate (SFP) aldolase,
      and 3-sulpholactaldehyde (SLA) reductase. The enzymes are encoded in a ten-gene
      cluster, which probably also encodes regulation, transport and degradation of the
      whole sulpholipid; the gene cluster is present in almost all (>91%) available E.
      coli genomes, and is widespread in Enterobacteriaceae. The pathway yields
      dihydroxyacetone phosphate (DHAP), which powers energy conservation and growth of
      E. coli, and the sulphonate product 2,3-dihydroxypropane-1-sulphonate (DHPS),
      which is excreted. DHPS is mineralized by other bacteria, thus closing the
      sulphur cycle within a bacterial community. 

PMID- 24463507
TI  - De novo mutations in schizophrenia implicate synaptic networks.
AB  - Inherited alleles account for most of the genetic risk for schizophrenia.
      However, new (de novo) mutations, in the form of large chromosomal copy number
      changes, occur in a small fraction of cases and disproportionally disrupt genes
      encoding postsynaptic proteins. Here we show that small de novo mutations,
      affecting one or a few nucleotides, are overrepresented among glutamatergic
      postsynaptic proteins comprising activity-regulated cytoskeleton-associated
      protein (ARC) and N-methyl-d-aspartate receptor (NMDAR) complexes. Mutations are
      additionally enriched in proteins that interact with these complexes to modulate
      synaptic strength, namely proteins regulating actin filament dynamics and those
      whose messenger RNAs are targets of fragile X mental retardation protein (FMRP).
      Genes affected by mutations in schizophrenia overlap those mutated in autism and
      intellectual disability, as do mutation-enriched synaptic pathways. Aligning our
      findings with a parallel case-control study, we demonstrate reproducible insights
      into aetiological mechanisms for schizophrenia and reveal pathophysiology shared
      with other neurodevelopmental disorders. 

PMID- 24463509
TI  - Ecology: plant diversity rooted in pathogens.

PMID- 24463508
TI  - A polygenic burden of rare disruptive mutations in schizophrenia.
AB  - Schizophrenia is a common disease with a complex aetiology, probably involving
      multiple and heterogeneous genetic factors. Here, by analysing the exome
      sequences of 2,536 schizophrenia cases and 2,543 controls, we demonstrate a
      polygenic burden primarily arising from rare (less than 1 in 10,000), disruptive
      mutations distributed across many genes. Particularly enriched gene sets include
      the voltage-gated calcium ion channel and the signalling complex formed by the
      activity-regulated cytoskeleton-associated scaffold protein (ARC) of the
      postsynaptic density, sets previously implicated by genome-wide association and
      copy-number variation studies. Similar to reports in autism, targets of the
      fragile X mental retardation protein (FMRP, product of FMR1) are enriched for
      case mutations. No individual gene-based test achieves significance after
      correction for multiple testing and we do not detect any alleles of moderately
      low frequency (approximately 0.5 to 1 per cent) and moderately large effect.
      Taken together, these data suggest that population-based exome sequencing can
      discover risk alleles and complements established gene-mapping paradigms in
      neuropsychiatric disease. 

PMID- 24463510
TI  - The evolution of lncRNA repertoires and expression patterns in tetrapods.
AB  - Only a very small fraction of long noncoding RNAs (lncRNAs) are well
      characterized. The evolutionary history of lncRNAs can provide insights into
      their functionality, but the absence of lncRNA annotations in non-model organisms
      has precluded comparative analyses. Here we present a large-scale evolutionary
      study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We
      identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved
      lncRNAs, including approximately 400 genes that are likely to have originated
      more than 300 million years ago. We find that lncRNAs, in particular ancient
      ones, are in general actively regulated and may function predominantly in
      embryonic development. Most lncRNAs evolve rapidly in terms of sequence and
      expression levels, but tissue specificities are often conserved. We compared
      expression patterns of homologous lncRNA and protein-coding families across
      tetrapods to reconstruct an evolutionarily conserved co-expression network. This
      network suggests potential functions for lncRNAs in fundamental processes such as
      spermatogenesis and synaptic transmission, but also in more specific mechanisms
      such as placenta development through microRNA production. 

PMID- 24463511
TI  - ANP32E is a histone chaperone that removes H2A.Z from chromatin.
AB  - H2A.Z is an essential histone variant implicated in the regulation of key nuclear
      events. However, the metazoan chaperones responsible for H2A.Z deposition and its
      removal from chromatin remain unknown. Here we report the identification and
      characterization of the human protein ANP32E as a specific H2A.Z chaperone. We
      show that ANP32E is a member of the presumed H2A.Z histone-exchange complex
      p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z
      through a new motif termed H2A.Z interacting domain (ZID). The 1.48 A resolution
      crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B
      dimer and biochemical data support an underlying molecular mechanism for
      H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a
      specific extension of the H2A.Z carboxy-terminal alpha-helix. Finally, analysis
      of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation
      followed by sequencing shows genome-wide enrichment, redistribution and
      accumulation of H2A.Z at specific chromatin control regions, in particular at
      enhancers and insulators. 

PMID- 24463513
TI  - An optical lattice clock with accuracy and stability at the 10(-18) level.
AB  - Progress in atomic, optical and quantum science has led to rapid improvements in
      atomic clocks. At the same time, atomic clock research has helped to advance the
      frontiers of science, affecting both fundamental and applied research. The
      ability to control quantum states of individual atoms and photons is central to
      quantum information science and precision measurement, and optical clocks based
      on single ions have achieved the lowest systematic uncertainty of any frequency
      standard. Although many-atom lattice clocks have shown advantages in measurement
      precision over trapped-ion clocks, their accuracy has remained 16 times worse.
      Here we demonstrate a many-atom system that achieves an accuracy of 6.4 * 10(
      18), which is not only better than a single-ion-based clock, but also reduces the
      required measurement time by two orders of magnitude. By systematically
      evaluating all known sources of uncertainty, including in situ monitoring of the
      blackbody radiation environment, we improve the accuracy of optical lattice
      clocks by a factor of 22. This single clock has simultaneously achieved the best
      known performance in the key characteristics necessary for consideration as a
      primary standard-stability and accuracy. More stable and accurate atomic clocks
      will benefit a wide range of fields, such as the realization and distribution of
      SI units, the search for time variation of fundamental constants, clock-based
      geodesy and other precision tests of the fundamental laws of nature. This work
      also connects to the development of quantum sensors and many-body quantum state
      engineering (such as spin squeezing) to advance measurement precision beyond the
      standard quantum limit.

PMID- 24463512
TI  - A discrete genetic locus confers xyloglucan metabolism in select human gut
      Bacteroidetes.
AB  - A well-balanced human diet includes a significant intake of non-starch
      polysaccharides, collectively termed 'dietary fibre', from the cell walls of
      diverse fruits and vegetables. Owing to the paucity of alimentary enzymes encoded
      by the human genome, our ability to derive energy from dietary fibre depends on
      the saccharification and fermentation of complex carbohydrates by the massive
      microbial community residing in our distal gut. The xyloglucans (XyGs) are a
      ubiquitous family of highly branched plant cell wall polysaccharides whose
      mechanism(s) of degradation in the human gut and consequent importance in
      nutrition have been unclear. Here we demonstrate that a single, complex gene
      locus in Bacteroides ovatus confers XyG catabolism in this common colonic
      symbiont. Through targeted gene disruption, biochemical analysis of all predicted
      glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional
      structural determination of the vanguard endo-xyloglucanase, we reveal the
      molecular mechanisms through which XyGs are hydrolysed to component
      monosaccharides for further metabolism. We also observe that orthologous XyG
      utilization loci (XyGULs) serve as genetic markers of XyG catabolism in
      Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically
      diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes.
      Our findings reveal that the metabolism of even highly abundant components of
      dietary fibre may be mediated by niche species, which has immediate fundamental
      and practical implications for gut symbiont population ecology in the context of
      human diet, nutrition and health. 

PMID- 24463514
TI  - A two-fold increase of carbon cycle sensitivity to tropical temperature
      variations.
AB  - Earth system models project that the tropical land carbon sink will decrease in
      size in response to an increase in warming and drought during this century,
      probably causing a positive climate feedback. But available data are too limited
      at present to test the predicted changes in the tropical carbon balance in
      response to climate change. Long-term atmospheric carbon dioxide data provide a
      global record that integrates the interannual variability of the global carbon
      balance. Multiple lines of evidence demonstrate that most of this variability
      originates in the terrestrial biosphere. In particular, the year-to-year
      variations in the atmospheric carbon dioxide growth rate (CGR) are thought to be
      the result of fluctuations in the carbon fluxes of tropical land areas. Recently,
      the response of CGR to tropical climate interannual variability was used to put a
      constraint on the sensitivity of tropical land carbon to climate change. Here we
      use the long-term CGR record from Mauna Loa and the South Pole to show that the
      sensitivity of CGR to tropical temperature interannual variability has increased
      by a factor of 1.9 +/- 0.3 in the past five decades. We find that this
      sensitivity was greater when tropical land regions experienced drier conditions.
      This suggests that the sensitivity of CGR to interannual temperature variations
      is regulated by moisture conditions, even though the direct correlation between
      CGR and tropical precipitation is weak. We also find that present terrestrial
      carbon cycle models do not capture the observed enhancement in CGR sensitivity in
      the past five decades. More realistic model predictions of future carbon cycle
      and climate feedbacks require a better understanding of the processes driving the
      response of tropical ecosystems to drought and warming. 

PMID- 24463515
TI  - Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic
      European.
AB  - Ancient genomic sequences have started to reveal the origin and the demographic
      impact of farmers from the Neolithic period spreading into Europe. The adoption
      of farming, stock breeding and sedentary societies during the Neolithic may have
      resulted in adaptive changes in genes associated with immunity and diet. However,
      the limited data available from earlier hunter-gatherers preclude an
      understanding of the selective processes associated with this crucial transition
      to agriculture in recent human evolution. Here we sequence an approximately 7,000
      year-old Mesolithic skeleton discovered at the La Brana-Arintero site in Leon,
      Spain, to retrieve a complete pre-agricultural European human genome. Analysis of
      this genome in the context of other ancient samples suggests the existence of a
      common ancient genomic signature across western and central Eurasia from the
      Upper Paleolithic to the Mesolithic. The La Brana individual carries ancestral
      alleles in several skin pigmentation genes, suggesting that the light skin of
      modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide
      evidence that a significant number of derived, putatively adaptive variants
      associated with pathogen resistance in modern Europeans were already present in
      this hunter-gatherer. 

PMID- 24463516
TI  - In situ identification of bipotent stem cells in the mammary gland.
AB  - The mammary epithelium undergoes profound morphogenetic changes during
      development. Architecturally, it comprises two primary lineages, the inner
      luminal and outer myoepithelial cell layers. Two opposing concepts on the nature
      of mammary stem cells (MaSCs) in the postnatal gland have emerged. One model,
      based on classical transplantation assays, postulates that bipotent MaSCs have a
      key role in coordinating ductal epithelial expansion and maintenance in the adult
      gland, whereas the second model proposes that only unipotent MaSCs identified by
      lineage tracing contribute to these processes. Through clonal cell-fate mapping
      studies using a stochastic multicolour cre reporter combined with a new three
      dimensional imaging strategy, we provide evidence for the existence of bipotent
      MaSCs as well as distinct long-lived progenitor cells. The cellular dynamics at
      different developmental stages support a model in which both stem and progenitor
      cells drive morphogenesis during puberty, whereas bipotent MaSCs coordinate
      ductal homeostasis and remodelling of the mouse adult gland. 

PMID- 24463517
TI  - A cosmic web filament revealed in Lyman-alpha emission around a luminous high
      redshift quasar.
AB  - Simulations of structure formation in the Universe predict that galaxies are
      embedded in a 'cosmic web', where most baryons reside as rarefied and highly
      ionized gas. This material has been studied for decades in absorption against
      background sources, but the sparseness of these inherently one-dimensional probes
      preclude direct constraints on the three-dimensional morphology of the underlying
      web. Here we report observations of a cosmic web filament in Lyman-alpha
      emission, discovered during a survey for cosmic gas fluorescently illuminated by
      bright quasars at redshift z ~ 2.3. With a linear projected size of approximately
      460 physical kiloparsecs, the Lyman-alpha emission surrounding the radio-quiet
      quasar UM 287 extends well beyond the virial radius of any plausible associated
      dark-matter halo and therefore traces intergalactic gas. The estimated cold gas
      mass of the filament from the observed emission-about 10(12.0 +/- 0.5)/C(1/2)
      solar masses, where C is the gas clumping factor-is more than ten times larger
      than what is typically found in cosmological simulations, suggesting that a
      population of intergalactic gas clumps with subkiloparsec sizes may be missing in
      current numerical models.

PMID- 24463518
TI  - Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell
      development.
AB  - In immune responses, activated T cells migrate to B-cell follicles and develop
      into follicular T-helper (TFH) cells, a recently identified subset of CD4(+) T
      cells specialized in providing help to B lymphocytes in the induction of germinal
      centres. Although Bcl6 has been shown to be essential in TFH-cell function, it
      may not regulate the initial migration of T cells or the induction of the TFH
      program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation.
      Here we show that expression of achaete-scute homologue 2 (Ascl2)--a basic helix
      loop-helix (bHLH) transcription factor--is selectively upregulated in TFH cells.
      Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C
      chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as
      accelerating T-cell migration to the follicles and TFH-cell development in vivo
      in mice. Genome-wide analysis indicates that Ascl2 directly regulates TFH-related
      genes whereas it inhibits expression of T-helper cell 1 (TH1) and TH17 signature
      genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3
      protein in CD4(+) T cells, results in impaired TFH-cell development and germinal
      centre response. Conversely, mutation of Id3, known to cause antibody-mediated
      autoimmunity, greatly enhances TFH-cell generation. Thus, Ascl2 directly
      initiates TFH-cell development.

PMID- 24463519
TI  - SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA
      methylation.
AB  - RNA-directed DNA methylation in Arabidopsis thaliana depends on the upstream
      synthesis of 24-nucleotide small interfering RNAs (siRNAs) by RNA POLYMERASE IV
      (Pol IV) and downstream synthesis of non-coding transcripts by Pol V. Pol V
      transcripts are thought to interact with siRNAs which then recruit DOMAINS
      REARRANGED METHYLTRANSFERASE 2 (DRM2) to methylate DNA. The SU(VAR)3-9 homologues
      SUVH2 and SUVH9 act in this downstream step but the mechanism of their action is
      unknown. Here we show that genome-wide Pol V association with chromatin
      redundantly requires SUVH2 and SUVH9. Although SUVH2 and SUVH9 resemble histone
      methyltransferases, a crystal structure reveals that SUVH9 lacks a peptide
      substrate binding cleft and lacks a properly formed S-adenosyl methionine (SAM)
      binding pocket necessary for normal catalysis, consistent with a lack of
      methyltransferase activity for these proteins. SUVH2 and SUVH9 both contain SRA
      (SET- and RING-ASSOCIATED) domains capable of binding methylated DNA, suggesting
      that they function to recruit Pol V through DNA methylation. Consistent with this
      model, mutation of DNA METHYLTRANSFERASE 1 (MET1) causes loss of DNA methylation,
      a nearly complete loss of Pol V at its normal locations, and redistribution of
      Pol V to sites that become hypermethylated. Furthermore, tethering SUVH9
      [corrected] with a zinc finger to an unmethylated site is sufficient to recruit
      Pol V and establish DNA methylation and gene silencing. These results indicate
      that Pol V is recruited to DNA methylation through the methyl-DNA binding SUVH2
      and SUVH9 proteins, and our mechanistic findings suggest a means for selectively
      targeting regions of plant genomes for epigenetic silencing.

PMID- 24463520
TI  - Citrullination regulates pluripotency and histone H1 binding to chromatin.
AB  - Citrullination is the post-translational conversion of an arginine residue within
      a protein to the non-coded amino acid citrulline. This modification leads to the
      loss of a positive charge and reduction in hydrogen-bonding ability. It is
      carried out by a small family of tissue-specific vertebrate enzymes called
      peptidylarginine deiminases (PADIs) and is associated with the development of
      diverse pathological states such as autoimmunity, cancer, neurodegenerative
      disorders, prion diseases and thrombosis. Nevertheless, the physiological
      functions of citrullination remain ill-defined, although citrullination of core
      histones has been linked to transcriptional regulation and the DNA damage
      response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear
      localization signal, was previously shown to act in myeloid cells where it
      mediates profound chromatin decondensation during the innate immune response to
      infection. Here we show that the expression and enzymatic activity of Padi4 are
      also induced under conditions of ground-state pluripotency and during
      reprogramming in mouse. Padi4 is part of the pluripotency transcriptional
      network, binding to regulatory elements of key stem-cell genes and activating
      their expression. Its inhibition lowers the percentage of pluripotent cells in
      the early mouse embryo and significantly reduces reprogramming efficiency. Using
      an unbiased proteomic approach we identify linker histone H1 variants, which are
      involved in the generation of compact chromatin, as novel PADI4 substrates.
      Citrullination of a single arginine residue within the DNA-binding site of H1
      results in its displacement from chromatin and global chromatin decondensation.
      Together, these results uncover a role for citrullination in the regulation of
      pluripotency and provide new mechanistic insights into how citrullination
      regulates chromatin compaction. 

PMID- 24463521
TI  - Within-group male relatedness reduces harm to females in Drosophila.
AB  - To resolve the mechanisms that switch competition to cooperation is key to
      understanding biological organization. This is particularly relevant for
      intrasexual competition, which often leads to males harming females. Recent
      theory proposes that kin selection may modulate female harm by relaxing
      competition among male relatives. Here we experimentally manipulate the
      relatedness of groups of male Drosophila melanogaster competing over females to
      demonstrate that, as expected, within-group relatedness inhibits male competition
      and female harm. Females exposed to groups of three brothers unrelated to the
      female had higher lifetime reproductive success and slower reproductive ageing
      compared to females exposed to groups of three males unrelated to each other.
      Triplets of brothers also fought less with each other, courted females less
      intensively and lived longer than triplets of unrelated males. However,
      associations among brothers may be vulnerable to invasion by minorities of
      unrelated males: when two brothers were matched with an unrelated male, the
      unrelated male sired on average twice as many offspring as either brother. These
      results demonstrate that relatedness can profoundly affect fitness through its
      modulation of intrasexual competition, as flies plastically adjust sexual
      behaviour in a manner consistent with kin-selection theory. 

PMID- 24463522
TI  - Pathogens and insect herbivores drive rainforest plant diversity and composition.
AB  - Tropical forests are important reservoirs of biodiversity, but the processes that
      maintain this diversity remain poorly understood. The Janzen-Connell hypothesis
      suggests that specialized natural enemies such as insect herbivores and fungal
      pathogens maintain high diversity by elevating mortality when plant species occur
      at high density (negative density dependence; NDD). NDD has been detected widely
      in tropical forests, but the prediction that NDD caused by insects and pathogens
      has a community-wide role in maintaining tropical plant diversity remains
      untested. We show experimentally that changes in plant diversity and species
      composition are caused by fungal pathogens and insect herbivores. Effective plant
      species richness increased across the seed-to-seedling transition, corresponding
      to large changes in species composition. Treating seeds and young seedlings with
      fungicides significantly reduced the diversity of the seedling assemblage,
      consistent with the Janzen-Connell hypothesis. Although suppressing insect
      herbivores using insecticides did not alter species diversity, it greatly
      increased seedling recruitment and caused a marked shift in seedling species
      composition. Overall, seedling recruitment was significantly reduced at high
      conspecific seed densities and this NDD was greatest for the species that were
      most abundant as seeds. Suppressing fungi reduced the negative effects of density
      on recruitment, confirming that the diversity-enhancing effect of fungi is
      mediated by NDD. Our study provides an overall test of the Janzen-Connell
      hypothesis and demonstrates the crucial role that insects and pathogens have both
      in structuring tropical plant communities and in maintaining their remarkable
      diversity. 

PMID- 24463523
TI  - Sessile alveolar macrophages communicate with alveolar epithelium to modulate
      immunity.
AB  - The tissue-resident macrophages of barrier organs constitute the first line of
      defence against pathogens at the systemic interface with the ambient environment.
      In the lung, resident alveolar macrophages (AMs) provide a sentinel function
      against inhaled pathogens. Bacterial constituents ligate Toll-like receptors
      (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate
      alveolar epithelial receptors, leading to recruitment of neutrophils that engulf
      pathogens. Because the AM-induced response could itself cause tissue injury, it
      is unclear how AMs modulate the response to prevent injury. Here, using real-time
      alveolar imaging in situ, we show that a subset of AMs attached to the alveolar
      wall form connexin 43 (Cx43)-containing gap junction channels with the
      epithelium. During lipopolysaccharide-induced inflammation, the AMs remained
      sessile and attached to the alveoli, and they established intercommunication
      through synchronized Ca(2+) waves, using the epithelium as the conducting
      pathway. The intercommunication was immunosuppressive, involving Ca(2+)-dependent
      activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar
      neutrophil recruitment and secretion of proinflammatory cytokines in the
      bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in
      which a subset of alveolus-attached AMs intercommunicates immunosuppressive
      signals to reduce endotoxin-induced lung inflammation. 

PMID- 24463524
TI  - Sequential evolution of bacterial morphology by co-option of a developmental
      regulator.
AB  - What mechanisms underlie the transitions responsible for the diverse shapes
      observed in the living world? Although bacteria exhibit a myriad of morphologies,
      the mechanisms responsible for the evolution of bacterial cell shape are not
      understood. We investigated morphological diversity in a group of bacteria that
      synthesize an appendage-like extension of the cell envelope called the stalk. The
      location and number of stalks varies among species, as exemplified by three
      distinct subcellular positions of stalks within a rod-shaped cell body: polar in
      the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here
      we show that a developmental regulator of Caulobacter crescentus, SpmX, is co
      opted in the genus Asticcacaulis to specify stalk synthesis either at the
      subpolar or bilateral positions. We also show that stepwise evolution of a
      specific region of SpmX led to the gain of a new function and localization of
      this protein, which drove the sequential transition in stalk positioning. Our
      results indicate that changes in protein function, co-option and modularity are
      key elements in the evolution of bacterial morphology. Therefore, similar
      evolutionary principles of morphological transitions apply to both single-celled
      prokaryotes and multicellular eukaryotes. 

PMID- 24463525
TI  - Predictability of antigenic evolution for H3N2 human influenza A virus.
AB  - Influenza A virus continues to pose a threat to public health. Since this virus
      can evolve escape mutants rapidly, it is desirable to predict the antigenic
      evolution for developing effective vaccines. Although empirical methods have been
      proposed and reported to predict the antigenic evolution more or less accurately,
      they did not provide much insight into the effects of unobserved mutations and
      the mechanisms of antigenic evolution. Here a theoretical method was introduced
      to predict the antigenic evolution of H3N2 human influenza A virus by evaluating
      de novo mutations through estimating the antigenic distance. The antigenic
      distance defined with the hemagglutination inhibition (HI) titer was estimated
      with antigenic models taking into account the volume, isoelectric point, relative
      solvent accessibility, and distances from receptor-binding sites (RBS) and N
      linked glycosylation sites (NGS) for amino acids in hemagglutinin 1 (HA1). When
      the best model with the optimized parameter values was used to predict the
      antigenic evolution for the dominant strains, the prediction accuracy was
      relatively low. However, there appeared to be an overall tendency that the amino
      acid sites with larger potential net effect on antigenicity were more likely to
      evolve and the amino acid changes with larger potential effect were more likely
      to take place, suggesting that natural selection may operate to enhance the
      antigenic evolution of H3N2 human influenza A virus. 

PMID- 24463526
TI  - Development of a system for discovery of genetic interactions for essential genes
      in Escherichia coli K-12.
AB  - Genetic interaction networks are especially useful for functional assignment of
      genes and gaining new insights into the systems-level organization of the cell.
      While studying interactions of nonessential genes can be relatively straight
      forward via use of deletion mutants, different approaches must be used to reveal
      interactions of essential genes due to their indispensability. One method shown
      to be useful for revealing interactions of essential genes requires tagging the
      query protein. However, this approach can be complicated by mutational effects of
      potential hypomorphic alleles. Here, we describe a pilot study for a new scheme
      of systematically studying the interactions of essential genes. Our method uses a
      low-copy, F-based, complementing plasmid, pFE604T, from which the essential gene
      is conditionally expressed. The essential gene is expressed at lower levels,
      producing a moderate growth defect in a query host. Secondary mutations are
      introduced into the query host by conjugation and the resultant exconjugants are
      scored for growth by imaging them over time. We report results from studying five
      essential query genes: dnaN, ftsW, trmD, yrfF and yjgP, showing (on average)
      interactions with nearly 80 nonessential genes. This system should prove useful
      for genome-wide analyses of other essential genes in E. coli K-12. 

PMID- 24463527
TI  - A halt in poly(A) shortening during S-adenosyl-L-methionine-induced translation
      arrest in CGS1 mRNA of Arabidopsis thaliana.
AB  - Cystathionine gamma-synthase (CGS) catalyzes the first committed step of
      methionine (Met) biosynthesis in plants. Expression of the Arabidopsis thaliana
      CGS1 gene is negatively feedback-regulated in response to the direct Met
      metabolite S-adenosyl-L-methionine (AdoMet). This regulation occurs at the step
      of mRNA stability during translation and is coupled with AdoMet-induced CGS1
      specific translation arrest. In general, mRNA decay is initiated by a shortening
      of the poly(A) tail. However, this process has not been studied in detail in
      cases where regulatory events, such as programmed translation arrest, are
      involved. Here, we report that the poly(A) tail of the full-length CGS1 mRNA
      showed an apparent increase from 50-80 nucleotides (nt) to 140-150 nt after the
      induction of CGS1 mRNA degradation. This finding was unexpected because mRNAs
      that are destined for degradation harbored longer poly(A) tail than mRNAs that
      were not targeted for degradation. The results suggest that poly(A) shortening is
      inhibited or delayed during AdoMet-induced translation arrest of CGS1 mRNA. We
      propose an explanation for this phenomenon that remains consistent with the
      recent model of actively translating mRNA. We also found that CGS1 mRNA
      degradation intermediates, which are 5'-truncated forms of CGS1 mRNA, had a short
      poly(A) tail of 10-30 nt. This suggests that poly(A) shortening occurs rapidly on
      the degradation intermediates. The present study highlights CGS1 mRNA degradation
      as a useful system to understand the dynamic features of poly(A) shortening. 

PMID- 24463528
TI  - Enzymatic characterization of recombinant alpha-amylase in the Drosophila
      melanogaster species subgroup: is there an effect of specialization on digestive
      enzyme?
AB  - We performed a comparative study on the enzymological features of purified
      recombinant alpha-amylase of three species belonging to the Drosophila
      melanogaster species subgroup: D. melanogaster, D. erecta and D. sechellia. D.
      erecta and D. sechellia are specialist species, with host plant Pandanus
      candelabrum (Pandanaceae) and Morinda citrifolia (Rubiaceae), respectively. The
      temperature optima were around 57-60C for the three species. The pH optima were
      7.2 for D. melanogaster, 8.2 for D. erecta and 8.5 for D. sechellia. The kcat and
      Km were also estimated for each species with different substrates. The specialist
      species D. erecta and D. sechellia display a higher affinity for starch than D.
      melanogaster. alpha-Amylase activity is higher on starch than on glycogen in all
      species. alpha-Amylases of D. erecta and D. sechellia have a higher activity on
      maltooligosaccharides (G6 and G7) than on starch, contrary to D. melanogaster.
      Such differences in the enzymological features between the species might reflect
      adaptation to different ecological niches and feeding habits. 

PMID- 24463529
TI  - The function of DrPax1b gene in the embryonic development of zebrafish.
AB  - Vertebrate Pax1 gene is a member of Pax gene family and encodes a transcription
      factor associated with crucial roles in the development of pharyngeal pouch,
      scletrotome and limb bud. In zebrafish, the genome contains two Pax1 paralogs,
      DrPax1a and DrPax1b, which share high sequence similarity with other Pax1 genes.
      To elucidate the function of zebrafish DrPax1b gene, we first examined the gene
      expression pattern and found that it was mainly expressed in the endodermal
      pharyngeal pouch, caudal somites, notochord, and fin bud. Then, we performed
      knockdown experiments using antisense morpholino oligonucleotides, which lead to
      the defects in the vertebral column, tail, pharyngeal skeleton, and pectoral fin.
      Additionally, we also found that the mouse MmPax1 mRNA, but not the amphioxus
      AmphiPax1/9 mRNA, could rescue the MO-induced defects. Furthermore, sequence
      alignment revealed that the N-terminal region of vertebrate Pax1 and amphioxus
      Pax1/9 were highly conserved, whereas their C-terminal regions were relatively
      divergent. However, the chimeric Am(N)Dr(C)Pax1, Mm(N)Dr(C)Pax1 and
      Dr(N)Mm(C)Pax1 mRNA could partially rescue the defects, while the Dr(N)Am(C)Pax1
      mRNA could not. In conclusion, our data demonstrate a conserved function of
      DrPax1b in the development of the vertebral column, pectoral fin and pharyngeal
      skeleton formation in zebrafish and also provide critical insight into the
      functional evolution of Pax1 gene by changing its C-terminal sequence. 

PMID- 24463530
TI  - Biofilm formation by Salmonella enterica serovar 1,4,[5],12:i:- Portuguese
      isolates: a phenotypic, genotypic, and socio-geographic analysis.
AB  - Biofilm-forming ability is well established as an important virulence factor.
      However, there are no studies available regarding biofilm formation of Salmonella
      Typhimurium 1,4,[5],12:i:-, the new pandemic serovar in Europe. To address this
      problem, biofilm expression by Salmonella 1,4,[5],12:i:- was evaluated using 133
      isolates from clinical, environmental and animal origins, collected in Portugal
      from 2006 to 2011. Biofilm detection was performed by phenotypic and genotypic
      methods, such growth characterization in agar and broth medium, optical density
      determination by microtiter assays and direct observation by fluorescent in situ
      hybridization. Biofilm-related genes adrA, csgD and gcpA were detected by PCR. A
      socio-geographic characterization of strains as biofilm producers was also
      performed. Results showed that biofilm formation in monophasic Salmonella is
      widely distributed in Portuguese isolates and could be one of the reasons for its
      dissemination in this country. Biofilm expression varies between locations,
      showing that isolates from some regions like Lisboa or Ponta Delgada have an
      increased ability to persist in the environment due to an enhanced biofilm
      production. Biofilm formation also varies between risk groups, with a higher
      prevalence in isolates from salmonellosis infections in women. Therefore, the
      analysis of the socio-geographic distribution of biofilm-forming bacteria should
      be considered for the establishment of more adequate regulatory measures or
      therapeutics regimens, especially important due to the continuous increase of
      infections caused by antimicrobial resistant microorganisms.

PMID- 24463531
TI  - The inhibitory effects of a new cobalt-based polyoxometalate on the growth of
      human cancer cells.
AB  - A new cobalt-based polyoxometalate,
      (Himi)2[Bi(2)W2(0)O(66)(OH)(4)Co2(H2O)(6)Na(4) (H2O)14] . 17H2O (imi = iminazole)
      (BWCN) has been synthesized and structurally characterized. The inhibitory
      activities against selected human cancer lines were also determined in this
      study. The cell viability and chemoresistance of BWCN on human colon carcinoma HT
      29 cells were assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazoliumbromide), cell morphology changes, a comet assay and western blot
      analysis. The typical morphologic changes of apoptosis and DNA damage indicated
      that BWCN could have a distinct proliferation inhibitory effect on cancer cells.
      BWCN as a chemotherapeutic agent also induced apoptosis on HT-29 cells and showed
      a significant expression of cleaved-caspase-3. These results suggested that the
      active site of BWCN is the polymeric anion based on the basic tectonic block
      {BiW(9)}, and the possible mechanism is related to the interference of DNA
      synthesis in cancer cells.

PMID- 24463532
TI  - In situ TEM observation of resistance switching in titanate based device.
AB  - After decades of efforts, the research on resistance switching (RS) behavior in
      transition metal oxides has shifted to the stage of verifying the proposed models
      by direct experimental evidences. In this paper, RS behavior and oxygen content
      variation of La0.85Sr0.15TiO3/SrTiO3:Nb (LSTO/STON) were investigated by in situ
      transmission electron microscopy observation and in situ electron energy loss
      spectrum characterization under external electric field. The oxygen content
      fluctuation adjusted by applied bias has been investigated and the observed
      results imply the conductive channels should be formed by the oxygen vacancy at
      the Pt/LSTO interface. Moreover, in situ TEM characterization displays the
      advantage - to reveal the origin of various RS behaviors. 

PMID- 24463534
TI  - Auxin-induced hydrogen sulfide generation is involved in lateral root formation
      in tomato.
AB  - Similar to auxin, hydrogen sulfide (H2S), mainly produced by l-cysteine
      desulfhydrase (DES; EC 4.4.1.1) in plants, could induce lateral root formation.
      The objective of this study was to test whether H2S is also involved in auxin
      induced lateral root development in tomato (Solanum lycopersicum L.) seedlings.
      We observed that auxin depletion-induced down-regulation of transcripts of
      SlDES1, decreased DES activity and endogenous H2S contents, and the inhibition of
      lateral root formation were rescued by sodium hydrosulfide (NaHS, an H2S donor).
      However, No additive effects were observed when naphthalene acetic acid (NAA) was
      co-treated with NaHS (lower than 10 mM) in the induction of lateral root
      formation. Subsequent work revealed that a treatment with NAA or NaHS could
      simultaneously induce transcripts of SlDES1, DES activity and endogenous H2S
      contents, and thereafter the stimulation of lateral root formation. It was
      further confirmed that H2S or HS(-), not the other sulfur-containing components
      derived from NaHS, was attributed to the stimulative action. The inhibition of
      lateral root formation and decreased of H2S metabolism caused by an H2S scavenger
      hypotaurine (HT) were reversed by NaHS, but not NAA. Molecular evidence revealed
      that both NaHS- or NAA-induced modulation of some cell cycle regulatory genes,
      including the up-regulation of SlCDKA;1, SlCYCA2;1, together with simultaneous
      down-regulation of SlKRP2, were differentially reversed by HT pretreatment. To
      summarize, above results clearly suggested that H2S might, at least partially,
      act as a downstream component of auxin signaling to trigger lateral root
      formation. 

PMID- 24463535
TI  - Is stored malate the quantitatively most important substrate utilised by
      respiration and ethanolic fermentation in grape berry pericarp during ripening?
AB  - A widely held view is that in grape pericarp glycolysis is inhibited during
      ripening, and that stored malate rather than sugars become the major substrate
      for respiration. In this study we determined what contribution stored malate
      could make to the substrate requirements of respiration and ethanolic
      fermentation in the pericarp of Cabernet Sauvignon berries during ripening. At a
      number of time points through development the amount of malate in the pericarp
      was measured. The change in malate content between each time point was then
      calculated, having first allowed for dilution arising from expansion of the
      fruit. The amount of CO2 that was released by the berry in the interval between
      each pair of time points was measured. It was found that the contribution that
      stored malate could make to the substrate requirements of respiration and
      ethanolic fermentation of grape pericarp was dependent on the stage of ripening.
      At the beginning of ripening stored malate could provide a greater proportion of
      substrate than later in ripening, and during the latter its contribution was
      relatively low. Therefore, stored malate was not the quantitatively most
      important substrate utilised by respiration and ethanolic fermentation in the
      pericarp of grape berries during most of ripening. It is likely that sugars
      provide the bulk of the deficit in substrate. Further, the increase in the
      respiratory quotient during most of ripening does not arise from the use of
      malate as main respiratory substrate. 

PMID- 24463536
TI  - Small-sized PdCu nanocapsules on 3D graphene for high-performance ethanol
      oxidation.
AB  - A one-pot solvothermal process has been developed for direct preparation of PdCu
      nanocapsules (with a size of ca. 10 nm) on three-dimensional (3D) graphene. Due
      to the 3D pore-rich network of graphene and the unique hollow structure of PdCu
      nanocapsules with a wall thickness of ca. 3 nm, the newly-prepared PdCu/3D
      graphene hybrids activated electrochemically have great electrocatalytic activity
      towards ethanol oxidation in alkaline media, much better than single-phase Pd and
      commercial E-TEK 20% Pt/C catalysts promising for application in direct ethanol
      fuel cells. 

PMID- 24463537
TI  - Unexpected structural motifs in diamine coordination compounds with allyllithium.
AB  - New diamine coordination compounds with phenyllithium and allyllithium are
      presented. One of them is the first diamine complex containing two different,
      simple organolithium reagents. The formation of this unexpected compound is
      explained using quantum chemical calculations. 

PMID- 24463538
TI  - Trends in statin therapy initiation during the period 2000-2010 in Israel.
AB  - PURPOSE: The aim of this population-based study is to describe trends in the
      characteristics and treatment patterns of statin initiators over the first decade
      of the 21st century. METHODS: New statin use was studied retrospectively using
      the database of Maccabi Healthcare Services (MHS), a large Israeli health
      maintenance organization. Statin initiators were defined as MHS members aged >=
      30 years who first purchased statins between 2000 and 2010. The starting dose was
      calculated in simvastatin equivalents based on the World Health Organization's
      daily defined dose index. Persistence was calculated as the percentage of days
      covered (PDC) with statins during the first year of therapy. RESULTS: Statin
      initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period
      2005-2010. The average age at therapy initiation decreased from 58.9 (+/- 12.0)
      to 54.5 (+/- 11.7) years, and the average (SD) baseline low-density lipoprotein
      cholesterol (LDL-C) decreased from 4.2 (+/- 1.1) to 4.0 (+/- 0.9) mmol/l during
      the study period. Women were on average 3 years older than men at treatment
      initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence
      of ischemic heart disease (IHD) decreased from 17.8 to 6.7 %, and diabetes
      prevalence increased from 8.6 to 15.7 %, peaking in 2008 (18.0 %). The PDC with
      statins ranged between 52.9 and 57.7 %. Simvastatin use at initiation increased
      from 27.5 % in 2000 to >90 % since 2002. Starting dose increased from 18.5 (+/-
      8.9) to 24.3 (+/- 13.7) mg simvastatin equivalent. CONCLUSIONS: Among the study
      population, statin initiators were increasingly characterized by a lower
      cardiovascular risk-namely, younger individuals without IHD and with a lower
      baseline LDL-C. These trends underscore the important shift towards statin
      initiation for primary prevention, as well as the need to balance between
      benefits and the potential side effect of statins.

PMID- 24463539
TI  - Safety of combination therapy with milrinone and esmolol for heart protection
      during percutaneous coronary intervention in acute myocardial infarction.
AB  - PURPOSE: Ischemia/reperfusion injury remains an untreated clinical problem in
      patients with acute myocardial infarction (AMI) despite significant advances in
      emergent revascularization through percutaneous coronary intervention (PCI).
      Pharmacological intervention for infarct size reduction is unavailable. We have
      identified that the medications milrinone and esmolol, when administered together
      at the beginning of the reperfusion, significantly decrease infarct size via
      reducing reperfusion injury in an experimental model. The present study tested
      the safety of combination therapy of milrinone and esmolol (M + E) in patients
      with AMI. METHODS: Sixteen subjects with AMI requiring PCI were consecutively
      recruited. M + E was intravenously infused simultaneously for 10 min started at 5
      min before anticipated angioplasty balloon inflation. Another 16 consecutively
      recruited AMI patients requiring PCI served as a placebo arm treated per routine
      clinical protocol. Blood pressure (BP) and heart rate (HR) were monitored
      continuously during PCI. RESULTS: M + E combination therapy resulted in a trend
      of non-significant reduction in BP compared with a control group. There was a
      modest but significant increase in HR at the later phase of M + E infusion
      compared with a control group. No significant cardiac arrhythmia was induced
      during M + E infusion. CONCLUSIONS: The combination therapy with M + E produces a
      minimal change in hemodynamics and appears safe as an adjunctive therapy to PCI
      in AMI patients. Further studies are warranted.

PMID- 24463540
TI  - Red cell distribution width in patients with nonalcoholic fatty liver disease.

PMID- 24463541
TI  - Neutrophil-to-lymphocyte ratio: an emerging prognostic factor of cirrhosis?

PMID- 24463543
TI  - Hematocrit levels and red blood cell indices in patients with nonalcoholic fatty
      liver disease.

PMID- 24463542
TI  - JAK2 exon 12 mutations were not found in liver transplant recipients with or
      without pretransplant portal vein thrombosis.

PMID- 24463545
TI  - Location and binding mechanism of an ESIPT probe 3-hydroxy-2-naphthoic acid in
      unsaturated fatty acid bound serum albumins.
AB  - The binding site and the binding mechanism of 3-hydroxy-2-naphthoic acid (3HNA)
      in oleic acid (OA) bound serum albumins (bovine serum albumin (BSA) and human
      serum albumin (HSA)) have been determined using steady state and time resolved
      emission of tryptophan residues (Trp) in proteins and the ESIPT emission of 3HNA.
      Time resolved anisotropy of the probe 3HNA and low temperature phosphorescence of
      Trp residues of BSA in OA bound BSA at 77K reveals a drastic change of the
      binding site of 3HNA in the ternary system compared to that in the free protein.
      3HNA binds near Trp213 in the ternary system whereas 3HNA binds near Trp134 in
      the free protein. The structure of OA bound BSA generated using docking
      methodology exhibits U-bend configuration of all bound OA. The docked pose of
      3HNA in the free protein and in OA bound albumins (ternary systems) and the
      concomitant perturbation of the structure of proteins around the binding region
      of 3HNA corroborate the enhanced ESIPT emission of 3HNA and the energy transfer
      efficiency from the donor Trp213 of BSA to 3HNA acceptor in 3HNA-OA-BSA system. 

PMID- 24463546
TI  - Dosimetric theory for tumor-to-lung shunt fraction calculation in yttrium-90
      radioembolization of noncirrhotic livers.

PMID- 24463547
TI  - IRMER versus ARSAC in opportunistic nuclear medicine research.

PMID- 24463550
TI  - Just to be sure.

PMID- 24463551
TI  - Gossip and ostracism promote cooperation in groups.
AB  - The widespread existence of cooperation is difficult to explain because
      individuals face strong incentives to exploit the cooperative tendencies of
      others. In the research reported here, we examined how the spread of reputational
      information through gossip promotes cooperation in mixed-motive settings. Results
      showed that individuals readily communicated reputational information about
      others, and recipients used this information to selectively interact with
      cooperative individuals and ostracize those who had behaved selfishly, which
      enabled group members to contribute to the public good with reduced threat of
      exploitation. Additionally, ostracized individuals responded to exclusion by
      subsequently cooperating at levels comparable to those who were not ostracized.
      These results suggest that the spread of reputational information through gossip
      can mitigate egoistic behavior by facilitating partner selection, thereby helping
      to solve the problem of cooperation even in noniterated interactions.

PMID- 24463552
TI  - Far-out thinking: generating solutions to distant analogies promotes relational
      thinking.
AB  - Is it possible to induce a mind-set that will affect relational thinking in a
      subsequent reasoning task involving unrelated materials? We investigated whether
      evaluating the validity of verbal analogies (Experiment 1a) or generating
      solutions for them (Experiment 1b) could induce a relational mind-set that would
      transfer to an unrelated picture-mapping task. The verbal analogies were based on
      either near or far semantic relations. We found that generating (but not
      evaluating) solutions for semantically distant analogies increased the proportion
      of relational mappings on the transfer task, even after we controlled for fluid
      intelligence and response time. Solving near analogies did not produce transfer.
      Generation of solutions to far analogies appears to provide a potent method for
      triggering a mind-set that can enhance relational thinking in a different task. 

PMID- 24463553
TI  - "Obesity is a disease": examining the self-regulatory impact of this public
      health message.
AB  - In the current work, we examined the impact of the American Medical Association's
      recent classification of obesity as a disease on weight-management processes.
      Across three experimental studies, we highlighted the potential hidden costs
      associated with labeling obesity as a disease, showing that this message,
      presented in an actual New York Times article, undermined beneficial weight-loss
      self-regulatory processes. A disease-based, relative to an information-based,
      weight-management message weakened the importance placed on health-focused
      dieting and reduced concerns about weight among obese individuals--the very
      people whom such public-health messages are targeting. Further, the decreased
      concern about weight predicted higher-calorie food choices. In addition, the
      disease message, relative to a message that obesity is not a disease, lowered
      body-image dissatisfaction, but this too predicted higher-calorie food choices.
      Thus, although defining obesity as a disease may be beneficial for body image,
      results from the current work emphasize the negative implications of this message
      for self-regulation.

PMID- 24463554
TI  - Optical origins of opposing facial expression actions.
AB  - Darwin theorized that emotional expressions originated as opposing functional
      adaptations for the expresser, not as distinct categories of social signals.
      Given that two thirds of the eye's refractive power comes from the cornea, we
      examined whether opposing expressive behaviors that widen the eyes (e.g., fear)
      or narrow the eyes (e.g., disgust) may have served as an optical trade-off,
      enhancing either sensitivity or acuity, thereby promoting stimulus localization
      ("where") or stimulus discrimination ("what"), respectively. An optical model
      based on eye apertures of posed fear and disgust expressions supported this
      functional trade-off. We then tested the model using standardized optometric
      measures of sensitivity and acuity. We demonstrated that eye widening enhanced
      stimulus detection, whereas eye narrowing enhanced discrimination, each at the
      expense of the other. Opposing expressive actions around the eye may thus reflect
      origins in an optical principle, shaping visual encoding at its earliest stage
      how light is cast onto the retina.

PMID- 24463555
TI  - Infants are not sensitive to synesthetic cross-modality correspondences: a
      comment on Walker et al. (2010).

PMID- 24463556
TI  - Preverbal infants are sensitive to cross-sensory correspondences: much ado about
      the null results of Lewkowicz and Minar (2014).

PMID- 24463557
TI  - A novel gene regulator, pyrrole-imidazole polyamide targeting ABCA1 gene
      increases cholesterol efflux from macrophages and plasma HDL concentration.
AB  - Pyrrole-imidazole (PI) polyamides are nuclease-resistant novel compounds that
      inhibit transcription factors by binding to the minor groove of DNA. A PI
      polyamide that targets mouse ABCA1 and increases ABCA1 gene expression was
      designed and evaluated as an agent to increase plasma HDL concentration. A PI
      polyamide was designed to bind the activator protein-2 binding site of the mouse
      ABCA1 promoter. The effect of this PI polyamide on ABCA1 expression was evaluated
      by real-time RT-PCR and Western blotting using RAW264 cells. In vivo effects of
      this polyamide on ABCA1 gene expression and plasma HDL level were examined in
      C57B6 mice. One milligram per kilogram of body weight of PI polyamide was
      injected via the tail veins every 2 days for 1 week, and plasma lipid profiles
      were evaluated. PI polyamide showed a specific binding to the target DNA in gel
      mobility shift assay. Treatment of RAW264 cells with 1.0 MUM PI polyamide
      significantly increased ABCA1 mRNA expression. PI polyamide also significantly
      increased apolipoprotein AI-mediated HDL biogenesis in RAW264 cells. Cellular
      cholesterol efflux mediated by apolipoprotein AI was significantly increased by
      the PI polyamide treatment. PI polyamide significantly increased expression of
      ABCA1 mRNA in the liver of C57B6 mice. Plasma HDL concentration was increased by
      PI polyamide administration. All of the HDL sub-fractions showed a tendency to
      increase after PI polyamide administration. The designed PI polyamide that
      targeted ABCA1 successfully increased ABCA1 expression and HDL biogenesis. This
      novel gene-regulating agent is promising as a useful compound to increase plasma
      HDL concentration. KEY MESSAGES: A novel pyrrole-imidazole (PI) polyamide binds
      to ABCA1. PI polyamide interfered with binding of AP-2alpha protein to the ABCA1
      gene promoter. PI polyamide inhibited the AP-2alpha-mediated reduction of ABCA1
      gene and protein expression. PI polyamide increased ABCA1 protein and
      apolipoprotein AI mediated HDL biogenesis. PI polyamide is a new gene regulator
      for the prevention of atherosclerotic diseases.

PMID- 24463558
TI  - Control of autophagy maturation by acid sphingomyelinase in mouse coronary
      arterial smooth muscle cells: protective role in atherosclerosis.
AB  - Recent studies have indicated a protective role of autophagy in regulating
      vascular smooth muscle cells homeostasis in atherogenesis, but the mechanisms
      controlling autophagy, particularly autophagy maturation, are poorly understood.
      Here, we investigated whether acid sphingomyelinase (ASM)-regulated lysosome
      function is involved in autophagy maturation in coronary arterial smooth muscle
      cells (CASMCs) in the pathogenesis of atherosclerosis. In coronary arterial wall
      of ASM-deficient (Smpd1-/-) mice on Western diet, there were high expression
      levels of both LC3B, a robust marker of autophagosomes (APs), and p62, a
      selective autophagy substrate, compared with those in wild-type (Smpd1+/+) mice.
      By Western blotting and flow cytometry, atherogenic stimulation of Smpd1+/+
      CASMCs with 7-ketocholesterol was found to significantly enhance LC3B expression
      and increase the content of both APs and autophagolysosomes (APLs). In Smpd1-/-
      CASMCs, such 7-ketocholesterol-induced increases in LC3B and p62 expression and
      APs were further augmented, but APLs formation was abolished. Analysis of
      fluorescence resonance energy transfer between fluorescence-labeled LC3B and
      Lamp1 (lysosome marker) showed that 7-ketocholesterol markedly induced fusion of
      APs with lysosomes in Smpd1+/+ CASMCs, which was abolished in Smpd1-/- CASMCs.
      Moreover, 7-ketocholesterol-induced expression of cell dedifferentiation marker
      vimentin and proliferation was enhanced in Smpd1-/- CASMCs compared with those in
      Smpd1+/+ CASMCs. Lastly, overexpression of ASM further increased APLs formation
      in Smpd1+/+ CASMCs and restored APLs formation in Smpd1-/- CASMCs indicating that
      increased ASM expression is highly correlated with enhanced APLs formation. Taken
      together, our data suggest that the control of lysosome trafficking and fusion by
      ASM is essential to a normal autophagic flux in CASMCs, which implicates that the
      deficiency of ASM-mediated regulation of autophagy maturation may result in
      imbalance of arterial smooth muscle cell homeostasis and thus serve as an
      important atherogenic mechanism in coronary arteries. KEY MESSAGES: Acid
      sphingomyelinase (ASM) controls autophagy maturation in smooth muscle cells. ASM
      maintains smooth muscle cell homeostasis and its contractile phenotype. ASM plays
      a protective role in smooth muscle dysfunction and atherosclerosis.

PMID- 24463559
TI  - Screening method to evaluate point-of-care human chorionic gonadotropin (hCG)
      devices for susceptibility to the hook effect by hCG beta core fragment:
      evaluation of 11 devices.
AB  - BACKGROUND: The predominant hCG variant in urine, hCG beta core fragment
      (hCGbetacf), has been demonstrated to cause false-negative results in qualitative
      point-of-care (POC) hCG devices. This is a major concern for healthcare
      professionals using POC pregnancy tests. We developed a screening method to
      evaluate qualitative POC hCG devices for their susceptibility to inhibition by
      hCGbetacf. Using this method, we evaluated the performance of 11 commonly used
      devices. METHODS: A wide range of purified hCG and hCGbetacf concentrations were
      mixed and tested on 2 POC devices. By use of those results, a screening method
      was defined and 9 additional POC devices were evaluated. Two solutions containing
      (a) 500 pmol/L (171 IU/L) intact hCG with 0 pmol/L hCGbetacf and (b) 500 pmol/L
      intact hCG with 500 000 pmol/L hCGbetacf were used to screen all POC devices.
      RESULTS: The OSOM and Cen-Med Elite devices were found to be most susceptible to
      false-negative results due to hCGbetacf. The BC Icon 20 and the Alere were the
      least susceptible. The remaining 7 were moderately affected. Devices that gave
      the strongest signal with hCGbetacf alone were those that were least likely to
      show a hook effect. CONCLUSIONS: The screening method put forth here can be used
      by device users and manufacturers to evaluate POC devices for inhibition by
      hCGbetacf. Of 11 devices evaluated, only 2 have been identified that exhibit
      minimal to no susceptibility to hCGbetacf.

PMID- 24463560
TI  - Isothermal recombinase polymerase amplification assay applied to the detection of
      group B streptococci in vaginal/anal samples.
AB  - BACKGROUND: Group B streptococcal infections are the leading cause of sepsis and
      meningitis in newborns. A rapid and reliable method for the detection of this
      pathogen at the time of delivery is needed for the early treatment of neonates.
      Isothermal amplification techniques such as recombinase polymerase amplification
      have advantages relative to PCR in terms of the speed of reaction and simplicity.
      METHODS: We studied the clinical performance of recombinase polymerase
      amplification for the screening of group B streptococci in vaginal/anal samples
      from 50 pregnant women. We also compared the limit of detection and the
      analytical specificity of this isothermal assay to real-time PCR (RT-PCR).
      RESULTS: Compared to RT-PCR, the recombinase polymerase amplification assay
      showed a clinical sensitivity of 96% and a clinical specificity of 100%. The
      limit of detection was 98 genome copies and the analytical specificity was 100%
      for a panel of 15 bacterial and/or fungal strains naturally found in the
      vaginal/anal flora. Time-to-result for the recombinase polymerase amplification
      assay was <20 min compared to 45 min for the RT-PCR assay; a positive sample
      could be detected as early as 8 min. CONCLUSIONS: We demonstrate the potential of
      isothermal recombinase polymerase amplification assay as a clinically useful
      molecular diagnostic tool that is simple and faster than PCR/RT-PCR. Recombinase
      polymerase amplification offers great potential for nucleic acid-based
      diagnostics at the point of care.

PMID- 24463561
TI  - Aneurysmal rupture of the costo-cervical trunk in a patient with
      neurofibromatosis type 1: A case report.
AB  - INTRODUCTION: Rupture of blood vessels associated with neurofibromatosis type 1
      (NF-1) is a rare but life threatening complication. We report the first case of
      an aneurysmal rupture from the costocervical trunk in a NF-1 patient treated by
      endovascular embolisation. PRESENTATION OF CASE: A 43 year-old gentleman with a
      past medical history of NF-1 presented with sudden onset left sided neck
      swelling. A computed tomography (CT) revealed a large cervical haematoma, which
      was causing airway compromise, requiring the patient to be intubated.
      Percutaneous embolisation of the bleeding vessel from the costo-cervical trunk
      was performed with successful haemostasis and no immediate complications. A
      repeat CT scan showed a reduction in the original cervical haematoma. However,
      six days post embolisation, the patient arrested with complete whiteout of the
      left hemithorax. DISCUSSION: CT angiography is the gold standard for diagnosis of
      an aneurysmal rupture in NF-1 patients, and percutaneous embolisation is the
      preferred modality in patients who are haemodynamically stable due to arterial
      fragility and high intra operative mortality rates. The increasing haemothorax
      could be explained by the original cervical haematoma draining down into the
      pleural space, or the possibility of a new second bleed. CONCLUSION: This is the
      first reported episode of bleeding from the costocervical trunk in NF-1 patients.
      Ruptured aneurysms require urgent CT angiography, if haemodynamically stable, and
      further input from the vascular surgeons and vascular radiologists.

PMID- 24463562
TI  - Oversized pseudocysts of the spleen: Report of two cases: Optimal management of
      oversized pseudocysts of the spleen.
AB  - INTRODUCTION: Pseudocysts of the spleen are usually asymptomatic and associated
      with a history of trauma, infection or infarction. In this report, we present two
      uncommon cases of solitary, oversized pseudocysts of the spleen. PRESENTATION OF
      CASE: Two patients (cases A and B), with symptoms of abdominal pain, were
      investigated. The laboratory and ultrasound examination confirmed the diagnosis
      of a large, non-parasitic splenic cyst in both cases. Computed tomography
      described an oversized pseudocyst occupying almost the entire splenic parenchyma
      in both cases and in patient A, the cyst was located in the splenic hilum. The
      medical history revealed a previous abdominal injury only in case A. The two
      patients underwent an open total splenectomy. The pathology examination verified
      the diagnosis of a non-parasitic splenic pseudocyst. DISCUSSION: Both patients
      presented with symptoms, in contrast to the majority of patients with splenic
      cysts. The medical history of patients with splenic pseudocysts does not always
      reveal the cause of the pseudocyst formation. Any type of spleen-sparing
      procedure is not easy to perform in cases of surgical and anatomical difficulty,
      because of recurrence and the risk of intractable bleeding from the spleen.
      CONCLUSION: Partial splenectomy is the recommended method for parenchymal
      preservation, but total splenectomy is preferred when the splenic cyst is
      oversized or cannot be excised with safety.

PMID- 24463563
TI  - Severe cardiogenic shock due to acute onset of an aorto-to-right atrial shunt in
      a patient with aortic valve endocarditis.
AB  - INTRODUCTION: Heart failure is the most common cause of death due to infective
      endocarditis. We report a case of a patient presenting with severe shock due to
      an infection-associated left-to-right cardiac shunt. PRESENTATION OF CASE: A 62
      year-old man, who underwent aortic valve replacement five years previously, was
      admitted to ICU due to acute hemodynamic deterioration. A few days earlier, he
      had a septic episode with blood cultures positive for Staphylococcus aureus and
      clinical features of infective endocarditis. In ICU, transthoracic
      echocardiography revealed shunting from the aortic root to the right atrium
      resulting in severe cardiogenic shock. DISCUSSION: This case report describes a
      near fatal complication of infective endocarditis, detected by routine use of
      transthoracic echocardiography. CONCLUSION: Our case outlines the relevance of
      early cardiac surgery strategies in patients with infective endocarditis and we
      briefly discuss the current literature.

PMID- 24463564
TI  - Influence of the lambda780nm laser light on the repair of surgical bone defects
      grafted or not with biphasic synthetic micro-granular hydroxylapatite+Beta
      Calcium triphosphate.
AB  - The treatment of bone loss due to different etiologic factors is difficult and
      many techniques aim to improve repair, including a wide range of biomaterials
      and, recently, photobioengineering. This work aimed to assess, through
      histological analysis The aim of this study was to assess, by light microscopy,
      the repair of bone defects grafted or not with biphasic synthetic micro-granular
      Calcium hydroxyapatite (HA)+Beta-TCP associated or not with Laser phototherapy -
      LPT (lambda780nm). Forty rats were divided into 4 groups each subdivided into 2
      subgroups according to the time of sacrifice (15 and 30days). Surgical bone
      defects were made on femur of each animal with a trephine drill. On animals of
      Clot group the defect was filled only by blood clot, on Laser group the defect
      filled with the clot was further irradiated. On animals of Biomaterial and
      Laser+Biomaterial groups the defect was filled by biomaterial and the last one
      was further irradiated (lambda780nm, 70mW, spot size~0.4cm(2), 20J/cm(2)-session,
      140J/cm(2)-treatment) in four points around the defect at 48-h intervals and
      repeated for 2weeks. At both 15th and 30th days following sacrifice, samples were
      taken and analyzed by light microscopy. Many similarities were observed
      histologically between groups on regards bone reabsorption and neoformation,
      inflammatory infiltrate and collagen deposition. The criterion degree of
      maturation, marked by the presence of basophilic lines, indicated that the use of
      LPT associated with HA+Beta TCP graft, resulted in more advanced stage of bone
      repair at the end of the experiment. 

PMID- 24463565
TI  - Structural analysis and reactivity of unusual tetrahedral intermediates enabled
      by SmI2-mediated reduction of barbituric acids: vinylogous N-acyliminium
      additions to alpha-hydroxy-N-acyl-carbamides.
AB  - Structural characterisation and reactivity of new tetrahedral intermediates based
      on a highly modular barbituric acid scaffold, formed via chemoselective electron
      transfer using the SmI2-H2O reagent, are reported. Lewis acid promoted cleavage
      of bicyclic alpha-amino alcohols affords vinylogous N-acyliminium ions, which
      undergo selective (>95 : 5, 1,4 over 1,2) capture with a suite of diverse
      nucleophiles in a practical sequence to biologically active uracil derivatives. 

PMID- 24463566
TI  - Major hepatectomy is safe for hepatocellular carcinoma in elderly patients with
      cirrhosis.
AB  - BACKGROUND: Because of an increasing aging population worldwide, a greater number
      of elderly patients are being considered for hepatic resection. The objective of
      this retrospective pair-matched study was to assess the influence of age on
      postoperative outcomes after major hepatectomy (resection of three or more
      Couinaud segments) in elderly patients with hepatocellular carcinoma (HCC) and
      cirrhosis. PATIENTS AND METHODS: A retrospective review of patient demographics,
      diagnoses, surgical treatments, and early postoperative outcomes was performed.
      RESULTS: A total of 208 HCC patients with cirrhosis underwent major hepatectomy
      between 2007 and 2012. The mortality rate was 3.57% in patients aged 70 years or
      more (group E) compared with 1.32% in those aged below 70 years (group Y;
      P=0.630). The overall complication rates were 53.57% in group E and 47.37% in
      group Y (P=0.427). Increasing age was independently associated with postoperative
      pneumonia (P<0.001), bacteremia (P=0.026), and respiratory failure requiring
      reintubation (P=0.028). A total of 25.00% of patients had a Clavien-Dindo
      classification grade of 3a or more in group E compared with 13.16% in group Y
      (P=0.040). In multivariate analysis, intraoperative red blood cell transfusion of
      5 U or more (P=0.016; hazard ratio 4.812; 95% confidence interval 1.332-17.384)
      was a predictor of higher morbidity in the elderly. CONCLUSION: With rigorous
      screening of patients and improvement of perioperative management and operative
      techniques, major hepatectomy can be safely performed on HCC patients aged 70
      years or more with liver cirrhosis. Intraoperative red blood cell transfusion of
      5 U or more was predictive of higher morbidity in the elderly. Surgeons should
      take care to minimize the likelihood of intraoperative blood transfusion in
      elderly patients.

PMID- 24463568
TI  - Linear triatomic [ZnBi2]4- in K4ZnBi2.
AB  - The linear triatomic [ZnBi2](4-) found in the diamagnetic K4ZnBi2 was prepared as
      the first discrete Zn-Bi Zintl cluster anion in the neat solid state from the
      unique K-Zn-Bi system. The tetraanionic trimer has sixteen valence electrons
      isovalent with CO2, accounting for its nearly linear triatomic structure (Zn-Bi
      Zn, 177.3(3) degrees ) and multiple Zn[double bond, length as m-dash]Bi bonds
      revealed by the unprecedentedly short bond length (2.553(3) A) and DFT pi-bonding
      analyses, on the basis of the established 16-electron counting rule for a linear
      triatomic species. The VASP theoretical calculations reveal that K4ZnBi2 is a
      narrow gap direct semiconductor that is expected to present promising optical
      properties. 

PMID- 24463567
TI  - MIF, a potential therapeutic target for rheumatoid arthritis?

PMID- 24463569
TI  - Spatio-temporal dynamics in collective frog choruses examined by mathematical
      modeling and field observations.
AB  - This paper reports theoretical and experimental studies on spatio-temporal
      dynamics in the choruses of male Japanese tree frogs. First, we theoretically
      model their calling times and positions as a system of coupled mobile
      oscillators. Numerical simulation of the model as well as calculation of the
      order parameters show that the spatio-temporal dynamics exhibits bistability
      between two-cluster antisynchronization and wavy antisynchronization, by assuming
      that the frogs are attracted to the edge of a simple circular breeding site.
      Second, we change the shape of the breeding site from the circle to rectangles
      including a straight line, and evaluate the stability of two-cluster and wavy
      antisynchronization. Numerical simulation shows that two-cluster
      antisynchronization is more frequently observed than wavy antisynchronization.
      Finally, we recorded frog choruses at an actual paddy field using our sound
      imaging method. Analysis of the video demonstrated a consistent result with the
      aforementioned simulation: namely, two-cluster antisynchronization was more
      frequently realized. 

PMID- 24463570
TI  - Coil embolization in precommunicating (A1) segment aneurysms of anterior cerebral
      artery.
AB  - INTRODUCTION: Precommunicating (A1) segment aneurysms of the anterior cerebral
      artery are rare and often pose technical challenges for coil embolization due to
      their distinctive configurations. Clinical and radiologic outcomes of treating
      such aneurysms through endovascular coil embolization are presented herein.
      METHODS: Data accruing prospectively from May 2002 to August 2013 yielded 48
      patients harboring 50 A1 segment aneurysms, each classified as proximal, middle,
      or distal by location. Clinical outcome of the patients and morphological outcome
      of the aneurysms were assessed, with emphasis on technical aspects of treatment.
      RESULTS: The aneurysms studied occupied either proximal (n = 39), middle (n = 6),
      or distal (n = 5). Proximal aneurysms were largely directed posteriorly (80 %),
      and most (97 %) were devoid of branches. Middle and distal aneurysms were
      associated with the medial lenticulostriate artery, cortical branches, or
      fenestrations. The preshaped "S" and steam-shaped "S" microcatheters facilitated
      aneurysm selection in 60 % of lesions. Single-microcatheter technique was most
      commonly applied for coil embolization (62 %), followed by balloon protection (16
      %). Successful aneurysmal occlusion could be achieved in 76 % of the patients,
      with no procedure-related morbidity and mortality. At final follow-up (mean
      interval, 29.9 months), stable aneurysmal occlusion was sustained in 93 % of the
      patients (40/43). CONCLUSION: A1 segment aneurysms are amenable to safe and
      efficacious endovascular coil embolization by adjusting procedural strategy to
      accommodate distinctive anatomic configurations.

PMID- 24463571
TI  - Normal centrolineal myelination of the callosal splenium reflects the development
      of the cortical origin and size of its commissural fibers.
AB  - INTRODUCTION: Commissural white matter fibers comprising the callosal splenium
      are diverse. Subsections of the splenium myelinate at different times, in a
      centrolineal manner. The aims of this study are to depict the normal callosal
      splenium myelination pattern and to distinguish the transient age-related mid
      splenium hypointensity from pathology. METHODS: We reviewed 131 consecutive brain
      MRIs in patients between ages 3 and 6 months from a single academic children's
      hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were
      excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2
      weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed.
      Regions of callosal splenium myelination manifested by T1 and T2 shortening were
      evaluated. Tractography was performed with seeds placed over the posterior, mid,
      and anterior splenium to define the origin, destination, and course of traversing
      fibers. RESULTS: Splenium signal varied significantly from 3 to 6 months, with
      distinct age-related trends. On T1WI, the splenium was hypointense at 3 months
      (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and
      hyperintense at 6 months (10/11). Tractography revealed three distinct white
      matter tract populations: medial occipital (posterior); precuneus, posterior
      cingulate, and medial temporal (middle); and postcentral gyri (anterior).
      CONCLUSION: Specific commissural fiber components of the splenium myelinate at
      different times. The transient developmental mid splenium hypointensity on T1WI
      corresponds to tracts from the associative cortex, principally the precuneus.
      Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal
      developmental phenomenon that should not be confused with pathologic lesions.

PMID- 24463572
TI  - Generation of bispecific IgG antibodies by structure-based design of an
      orthogonal Fab interface.
AB  - Robust generation of IgG bispecific antibodies has been a long-standing
      challenge. Existing methods require extensive engineering of each individual
      antibody, discovery of common light chains, or complex and laborious biochemical
      processing. Here we combine computational and rational design approaches with
      experimental structural validation to generate antibody heavy and light chains
      with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating
      these interfaces, when simultaneously co-expressed, assemble into bispecific IgG
      with improved heavy chain-light chain pairing. Bispecific IgGs generated with
      this approach exhibit pharmacokinetic and other desirable properties of native
      IgG, but bind target antigens monovalently. As such, these bispecific reagents
      may be useful in many biotechnological applications. 

PMID- 24463574
TI  - Improving CRISPR-Cas nuclease specificity using truncated guide RNAs.
AB  - Clustered, regularly interspaced, short palindromic repeat (CRISPR) RNA-guided
      nucleases (RGNs) are highly efficient genome editing tools. CRISPR-associated 9
      (Cas9) RGNs are directed to genomic loci by guide RNAs (gRNAs) containing 20
      nucleotides that are complementary to a target DNA sequence. However, RGNs can
      induce mutations at sites that differ by as many as five nucleotides from the
      intended target. Here we report that truncated gRNAs, with shorter regions of
      target complementarity <20 nucleotides in length, can decrease undesired
      mutagenesis at some off-target sites by 5,000-fold or more without sacrificing on
      target genome editing efficiencies. In addition, use of truncated gRNAs can
      further reduce off-target effects induced by pairs of Cas9 variants that nick DNA
      (paired nickases). Our results delineate a simple, effective strategy to improve
      the specificities of Cas9 nucleases or paired nickases. 

PMID- 24463575
TI  - Low nitrogen fertilization adapts rice root microbiome to low nutrient
      environment by changing biogeochemical functions.
AB  - Reduced fertilizer usage is one of the objectives of field management in the
      pursuit of sustainable agriculture. Here, we report on shifts of bacterial
      communities in paddy rice ecosystems with low (LN), standard (SN), and high (HN)
      levels of N fertilizer application (0, 30, and 300 kg N ha(-1), respectively).
      The LN field had received no N fertilizer for 5 years prior to the experiment.
      The LN and HN plants showed a 50% decrease and a 60% increase in biomass compared
      with the SN plant biomass, respectively. Analyses of 16S rRNA genes suggested
      shifts of bacterial communities between the LN and SN root microbiomes, which
      were statistically confirmed by metagenome analyses. The relative abundances of
      Burkholderia, Bradyrhizobium and Methylosinus were significantly increased in
      root microbiome of the LN field relative to the SN field. Conversely, the
      abundance of methanogenic archaea was reduced in the LN field relative to the SN
      field. The functional genes for methane oxidation (pmo and mmo) and plant
      association (acdS and iaaMH) were significantly abundant in the LN root
      microbiome. Quantitative PCR of pmoA/mcrA genes and a (13)C methane experiment
      provided evidence of more active methane oxidation in the rice roots of the LN
      field. In addition, functional genes for the metabolism of N, S, Fe, and aromatic
      compounds were more abundant in the LN root microbiome. These results suggest
      that low-N-fertilizer management is an important factor in shaping the microbial
      community structure containing key microbes for plant associations and
      biogeochemical processes in paddy rice ecosystems. 

PMID- 24463573
TI  - Smac mimetics and innate immune stimuli synergize to promote tumor death.
AB  - Smac mimetic compounds (SMC), a class of drugs that sensitize cells to apoptosis
      by counteracting the activity of inhibitor of apoptosis (IAP) proteins, have
      proven safe in phase 1 clinical trials in cancer patients. However, because SMCs
      act by enabling transduction of pro-apoptotic signals, SMC monotherapy may be
      efficacious only in the subset of patients whose tumors produce large quantities
      of death-inducing proteins such as inflammatory cytokines. Therefore, we reasoned
      that SMCs would synergize with agents that stimulate a potent yet safe "cytokine
      storm." Here we show that oncolytic viruses and adjuvants such as poly(I:C) and
      CpG induce bystander death of cancer cells treated with SMCs that is mediated by
      interferon beta (IFN-beta), tumor necrosis factor alpha (TNF-alpha) and/or TNF
      related apoptosis-inducing ligand (TRAIL). This combinatorial treatment resulted
      in tumor regression and extended survival in two mouse models of cancer. As these
      and other adjuvants have been proven safe in clinical trials, it may be
      worthwhile to explore their clinical efficacy in combination with SMCs. 

PMID- 24463576
TI  - Characterization of early microbial communities on volcanic deposits along a
      vegetation gradient on the island of Miyake, Japan.
AB  - The 2000 eruption of Mount Oyama on the island of Miyake (Miyake-jima) created a
      unique opportunity to study the early ecosystem development on newly exposed
      terrestrial substrates. In this study, bacterial and fungal communities on 9- and
      11-year-old volcanic deposits at poorly to fully vegetation-recovered sites in
      Miyake-jima, Japan, were characterized by conventional culture-based methods and
      pyrosequencing of 16S rRNA and 18S rRNA genes. Despite the differences in the
      vegetation cover, the upper volcanic deposit layer samples displayed low among
      site variation for chemical properties (pH, total organic carbon, and total
      nitrogen) and microbial population densities (total direct count and culturable
      count). Statistical analyses of pyrosequencing data revealed that the microbial
      communities of volcanic deposit samples were phylogenetically diverse, in spite
      of very low-carbon environmental conditions, and their diversity was comparable
      to that in the lower soil layer (buried soil) samples. Comparing with the
      microbial communities in buried soil, the volcanic deposit communities were
      characterized by the presence of Betaproteobacteria and Gammaproteobacteria as
      the main bacterial class, Deinococcus- Thermus as the minor bacterial phyla, and
      Ascomycota as the major fungal phyla. Multivariate analysis revealed that several
      bacterial families and fungal classes correlated positively or negatively with
      plant species. 

PMID- 24463577
TI  - Computer-based prevention of intimate partner violence in marriage.
AB  - OBJECTIVE: Intimate partner violence (IPV) is a common, costly societal problem.
      Interventions designed to reduce IPV recidivism have had limited success but
      primary prevention efforts are likely to be more effective in reducing the
      occurrence of IPV. The purpose of this study was to examine the impact of a
      computer-based preventive intervention (ePREP) on IPV in a sample of married,
      community couples. METHOD: We employed a randomized clinical trial design
      comparing ePREP to an active placebo control group. Using a community sample of
      52 married couples (21% Black, 3% Asian, 65% White, 7% Latino, 4% Mixed/biracial)
      who had been married, on average, 4.3 years, we examined the impact ePREP on IPV
      as measured by self and partner reports of the Revised Conflict Tactics Scale. We
      assessed couples at baseline, six-weeks post-baseline, and one-year post
      baseline. We used the Actor Partner Interdependence Model with treatment effects
      to analyze the obtained dyadic data. RESULTS: We found that ePREP reduced
      physical and psychological aggression among married couples (on average across
      informants, a 90% reduction in expected counts of physical aggression, and a 0.18
      standard deviation reduction in psychological aggression) and that these gains
      were maintained at a 1-year follow-up assessment. CONCLUSIONS: Interventions that
      can be delivered widely and at a low-cost will increase the likelihood of
      reaching those who will benefit most from receiving them. Implications for
      implementing flexible interventions and changing our approach to treatment
      delivery are discussed.

PMID- 24463579
TI  - One-way rotation of a molecule-rotor driven by a shot noise.
AB  - The shot noise of a tunneling current passing through a molecule-motor can
      sustain a one-way rotation when populating the molecular excited states by
      tunneling inelastic excitations. We demonstrate that a ratchet-like ground state
      rotation potential energy curve is not necessary for the rotation to occur. A
      relative shift in energy difference between the maxima of this ground state and
      the minima of the excited states is the necessary condition to get to a
      unidirectional rotation. The rotor speed of rotation and its rotation direction
      are both controlled by this shift, indicating the necessity of a careful design
      of both the ground and excited states of the next generation of molecule-motors
      to be able to generate a motive power at the nanoscale. 

PMID- 24463580
TI  - Time for a comprehensive approach to the syndrome of fever in the tropics.

PMID- 24463578
TI  - Utilizing multiple in silico analyses to identify putative causal SCN5A variants
      in Brugada syndrome.
AB  - Brugada syndrome (BrS) is an inheritable sudden cardiac death disease mainly
      caused by SCN5A mutations. Traditional approaches can be costly and time
      consuming if all candidate variants need to be validated through in vitro
      studies. Therefore, we developed a new approach by combining multiple in silico
      analyses to predict functional and structural changes of candidate SCN5A variants
      in BrS before conducting in vitro studies. Five SCN5A non-synonymous variants
      (1651G>A, 1776C>G, 1673A>G, 3269C>T and 3578G>A) were identified in 14 BrS
      patients using direct DNA sequencing. Several bioinformatics algorithms were
      applied and predicted that 1651G>A (A551T) and 1776C>G (N592K) were high-risk
      SCN5A variants (odds ratio 59.59 and 23.93). The results were validated by Mass
      spectrometry and in vitro electrophysiological assays. We concluded that
      integrating sequence-based information and secondary protein structures elements
      may help select highly potential variants in BrS before conducting time-consuming
      electrophysiological studies and two novel SCN5A mutations were validated.

PMID- 24463581
TI  - Diagnosis of gnathostomiasis by skin testing using partially purified specific
      antigen and total IgE levels.
AB  - BACKGROUND: A finding of antibodies to Gnathostoma spinigerum 24-kDa antigen by
      immunoblot analysis is currently used to confirm a diagnosis of gnathostomiasis.
      A simple skin test for the diagnosis of gnathostomiasis was developed, and the
      results were evaluated and compared with the standard Western blot (WB) test.
      METHODS: This cross-sectional study was conducted at the Hospital for Tropical
      Diseases, Bangkok, Thailand, in 2008-2011. All eligible patients were tested with
      partially purified proteins of mAb-detected fractions pooled and sterilized by
      0.2 MUm diameter syringe filter, with a phenol saline solution of 1:10 w/v.
      RESULTS: A total of 69 cases, 39 gnathostomiasis cases and 30 controls, were
      enrolled into the study; the median age (IQR) was 40 (30.5-52.5) years. The most
      common presenting symptom was edema (56/69, 81%). Gnathostomiasis cases having
      strong cutaneous reactions to the intradermal test (81%) were also positive by
      immunoblot. A significant correlation between skin and immunoblot tests was
      detected (p<0.001). The difference in total IgE levels between cases and controls
      was not statistically significant (p=0.51). Logistic regression models showed
      that positive WB and skin-test results were significantly associated with
      gnathostomiasis (p=0.001 and p=0.007, respectively). CONCLUSION: Gnathostoma skin
      testing, using prepared fractionated antigen solution of Gnathostoma spinigerum,
      yields good reactivity and significantly correlates with the results of
      immunoblot testing.

PMID- 24463582
TI  - Efficacy of various insecticides recommended for indoor residual spraying:
      pirimiphos methyl, potential alternative to bendiocarb for pyrethroid resistance
      management in Benin, West Africa.
AB  - BACKGROUND: Using the same insecticide for multiple successive indoor residual
      spraying (IRS) cycles is not recommended; instead, the National Malaria Control
      Program (NMCP) has decided to select another insecticide (insecticide B) in
      addition to bendiocarb for indoor residual spraying. METHODS: An experimental hut
      trial comparing the effectiveness of three classes of insecticides (one carbamate
      [bendiocarb], two organophosphates [fenitrothion and pirimiphos methyl] and one
      pyrethroid [lambdacyalothrin]) was conducted in Malanville, northern Benin,
      against wild free entered resistant Anopheles gambiae s.l. population to
      pyrethroids. RESULTS: Fenitrothion and pirimiphos methyl yielded the highest rate
      of deterrence. Their mean rates were respectively 46.6% and 35.4%. Regarding
      blood feeding inhibition, only fenitrothion has induced a significant inhibition
      rate (25.4% as mean rate). As regards the exophily rates, only lambdacyhalothrin
      has induced the highest rate (39.7%). Pirimiphos methyl showed the highest
      mortality rate and also induced a mortality rate of at least 80% in blood fed An.
      gambiae population after 24 h observation time. Furthermore, the huts treated
      with pirimiphos methyl showed the highest residual effect, followed by
      lambdacyhalothrin. CONCLUSION: Benin NMCP has selected pirimiphos methyl as
      insecticide B to alternate or combine to bendiocarb (carbamate) because of the
      adverse effects of fenitrothion on the sleepers and its short residual effect on
      walls.

PMID- 24463583
TI  - Immunoreaction of a recombinant nanobody from camelid single domain antibody
      fragment with Acinetobacter baumannii.
AB  - BACKGROUND: Acinetobacter baumannii, an important nosocominal pathogen, causes
      various human infections like meningitis, bacteremia and pneumonia. The aim of
      this study was to produce nanobodies derived from camel heavy chain antibodies
      (HcAb) against a conserved region of the biofilm associated protein (Bap) of A.
      baumannii, by phage display technique. METHODS: A camel was immunized with the
      purified recombinant protein expressed from the conserved region of Bap and
      polyclonal antibody production was confirmed by ELISA. After RNA extraction from
      peripheral lymphocytes, cDNA was prepared and a phagemid library was constructed.
      RESULTS: Phage particles encoding nanobodies were produced by infecting
      transformed cells with a M13K07 helper phage. A total of six panning rounds were
      performed to select high affinity clones. Screening of high affinity monoclonal
      nanobodies was performed using phage-ELISA. A clone with the highest absorption
      in monoclonal phage-ELISA was selected for soluble expression of the desired
      nanobody. CONCLUSIONS: This is the first report on the expression and production
      of nanobodies against Bap. Increasing trends of drug resistance have shifted the
      focus to the role of antibodies in diagnosis and treatment of human diseases.
      Similarities of the produced VHH to human VH, makes the role of this nanobody
      promising in immunotherapy.

PMID- 24463584
TI  - Recent and future environmental suitability to dengue fever in Brazil using
      species distribution model.
AB  - BACKGROUND: Dengue fever is a mosquito-borne disease that affects more than 2.5
      billion people worldwide. Here, we used the dataset of municipality infestation
      level from the Brazilian Health Ministry with the aim of building vector
      distribution models to identify epidemiological hotspots. METHODS: Maxent
      software was used to predict the environmental suitability of the vector under
      current and 2050 climatic conditions. We built potential risk maps for current
      and future epidemiological scenarios in order to provide data for vector control
      planning. RESULTS: The results showed that the current epidemiological status is
      critical in the coastal region, with 80% of the population in risk areas and 30%
      in epidemiological outbreak areas. Our results also suggest that the area covered
      by the vector distribution in Brazil will decrease in future projections in the
      north, but will spread to the south. CONCLUSIONS: The results may provide useful
      information for health agencies and policymakers in focusing efforts in
      epidemiological hotspots. Therefore, understanding the niche distribution
      dynamics of Aedes aegypti is an important step towards public health planning for
      vector control.

PMID- 24463585
TI  - The challenge of the hospital chargemaster.

PMID- 24463586
TI  - Employee age and tenure within organizations: relationship to workplace
      satisfaction and workplace climate perceptions.
AB  - This study estimated the relative influence of age/generation and tenure on job
      satisfaction and workplace climate perceptions. Data from the 2004, 2008, and
      2012 Veterans Health Administration All Employee Survey (sample sizes >100 000)
      were examined in general linear models, with demographic characteristics
      simultaneously included as independent variables. Ten dependent variables
      represented a broad range of employee attitudes. Age/generation and tenure
      effects were compared through partial eta(2) (95% confidence interval), P value
      of F statistic, and overall model R(2). Demographic variables taken together were
      only weakly related to employee attitudes, accounting for less than 10% of the
      variance. Consistently across survey years, for all dependent variables, age and
      age-squared had very weak to no effects, whereas tenure and tenure-squared had
      meaningfully greater partial eta(2) values. Except for 1 independent variable in
      1 year, none of the partial eta(2) confidence intervals for age and age-squared
      overlapped those of tenure and tenure-squared. Much has been made in the popular
      and professional press of the importance of generational differences in workplace
      attitudes. Empirical studies have been contradictory and therefore inconclusive.
      The findings reported here suggest that age/generational differences might not
      influence employee perceptions to the extent that human resource and management
      practitioners have been led to believe.

PMID- 24463587
TI  - Dress codes and appearance policies: challenges under federal legislation, part
      2: title VII of the civil rights act and gender.
AB  - As more and more individuals express themselves with tattoos and body piercings
      and push the envelope on what is deemed appropriate in the workplace, employers
      have an increased need for creation and enforcement of reasonable dress codes and
      appearance policies. As with any employment policy or practice, an appearance
      policy must be implemented and enforced without regard to an individual's race,
      color, gender, national origin, religion, disability, age, or other protected
      status. A policy governing dress and appearance based on the business needs of an
      employer that is applied fairly and consistently and does not have a
      disproportionate effect on any protected class will generally be upheld if
      challenged in court. By examining some of the more common legal challenges to
      dress codes and how courts have resolved the disputes, health care managers can
      avoid many potential problems. This article, the second part of a 3-part
      examination of dress codes and appearance policies, focuses on the issue of
      gender under the Civil Rights Act of 1964. Pertinent court cases that provide
      guidance for employers are addressed. 

PMID- 24463588
TI  - Organizational factors influencing health information technology adoption in long
      term-care facilities.
AB  - Long-term care (LTC) is an important sector of the health care industry. However,
      the adoption of health information technology (HIT) systems in LTC facilities
      lags behind that in other sectors of health care. Previous literature has focused
      on the financial and technical barriers. This study examined the organizational
      factors associated with HIT adoption in LTC facilities. A survey of 500 LTC
      facilities in Texas enabled researchers to compile HIT indexes for further
      statistical analyses. A general linear model was used to study the associations
      between the clinical/administrative HIT indexes and organizational factors. The
      empirical outcomes show that the size of an LTC facility has a significant
      association with HIT adoption. Rural LTC facilities, especially freestanding
      ones, adopt less HIT than their urban counterparts, whereas freestanding LTC
      facilities have the lowest HIT adoption overall. There is not enough evidence to
      support ownership status as a significant factor in HIT adoption. Some
      implications are proposed, but further research is necessary. 

PMID- 24463589
TI  - Antecedents of care by physicians.
AB  - The objective of this study was to examine factors impacting physicians' quality
      of care. This study used the Center for Studying Health System Change's 2008
      Health Tracking Physician Survey data set consisting of 4720 physicians belonging
      to the American Medical Association. Regression analysis indicated that time with
      patient, career satisfaction, use of information technology for patient
      information, and income had a significant, positive impact on perception of high
      quality care by physicians. Threat of malpractice lawsuits, percent revenue from
      Medicaid, and type of practice had a significant negative impact on perception of
      high-quality care by physicians. Among all the variables examined in our study,
      time with patient had the greatest impact on perception of high-quality care by
      physicians. 

PMID- 24463591
TI  - Patient service navigator: improving quality and services and reducing cost under
      the Affordable Care Act.
AB  - This article proposes the implementation of a Patient Service Navigator to
      improve quality, service, and the patient and family experience and to reduce
      costs in caring for patients in a hospital setting. Under the Affordable Care
      Act, the Patient Service Navigator is a means to address value-based purchasing
      whereby hospitals will be reimbursed based on quality and Hospital Consumer
      Assessment of Healthcare Providers and System scores for Medicare patients. In
      this article, the reader will learn the history, background, purpose, and role of
      the Patient Service Navigator as a critical component of a multidisciplinary
      health care team in supporting inpatient care with a human touch. Navigating for
      the patient and family in a confusing and complex health care delivery
      environment is critical today in order to survive the mandates of the Affordable
      Care Act. 

PMID- 24463592
TI  - Task conflicts and exclusive professionalism in nursing in South Korea.
AB  - Task conflicts among medical professions are essential problems to be solved in
      health care organizations. This study examined job conflicts between practical
      nurses (PNs) and registered nurses (RNs) in their duties and tasks with
      representative panelists from South Korea. This qualitative study used the Dacum
      Task Analysis process. Subject-matter experts in practical nursing were recruited
      utilizing stratified sampling: Ten experts developed job descriptions of PNs, and
      20 validated the descriptions. The on-site tasks and duties of the PNs were
      measured by means of Dacum, and the results were reviewed by RNs using 3 focus
      group interviews. The job description of PNs consisted of 10 duties and 117
      tasks, overlapping with some tasks of RNs. Core tasks performed by PNs, such as
      invasive activities, led to task conflicts between the 2 groups, as these
      activities were regarded as the inherent duty of nursing professions. Thus, the
      RNs did not concede the expanded job scope of the PNs in terms of exclusive
      professionalism. To reduce task conflict, there is a need for the balanced
      development of nursing professionalism. 

PMID- 24463593
TI  - Willingness to participate in accountable care organizations: health care
      managers' perspective.
AB  - This study examines how health care managers responded to the accountable care
      organization (ACO). The effect of perceived benefits and barriers of the
      commitment to develop a strategic plan for ACOs and willingness to participate in
      ACOs is analyzed, using organizational social capital, health information
      technology uses, health systems integration and size of the health networks,
      geographic factors, and knowledge about ACOs as predictors. Propensity score
      matching and analysis are used to adjust the state and regional variations. When
      the number of perceived benefits is greater than the number of perceived
      barriers, health care managers are more likely to reveal a stronger commitment to
      develop a strategic plan for ACO adoption. Health care managers who perceived
      their organizations as lacking leadership support or commitment, financial
      incentives, and legal and regulatory support to ACO adoption were less willing to
      participate in ACOs in the future. Future research should gather more diverse
      views from a larger sample size of health professionals regarding ACO
      participation. The perspective of health care managers should be seriously
      considered in the adoption of an innovative health care delivery system. The
      transparency on policy formulation should consider multiple views of health care
      managers. 

PMID- 24463594
TI  - A causal model of antecedents with burnout focusing on the intermediate role of
      hardy personality in Iranian nurses.
AB  - Nowadays burnout is a common issue in all health systems and therapeutic
      professions. Burnout is caused by job stressors and results in reduction in
      output, increase in absenteeism and health expenses, behavioral changes, and
      sometimes drugs abuse. Nonetheless, people who have hardy personalities
      experience less exhaustion. The present research aimed to present a causal model
      of antecedents with burnout to emphasize the intermediate role of hardy
      personality in the nurses working in the public hospitals of Shiraz, Iran. The
      study data were collected using the Nursing Burnout Scale questionnaire (Int J
      Nurs Stud. 2008;45(3):418-427). In addition, the structural equation method was
      used as a model in order to determine the relationship between the variables. The
      suggested pattern in this research was checked by Leasrel software, version 8.5.
      The study results showed that antecedents, such as incorrect supervision,
      responsibility, and workload, have a significant effect on burnout. However,
      mediated hardy personality had no effect on burnout. The results also showed that
      the people who had hardy personality could manage the stressful situations well
      and, consequently, rarely experience burnout. Overall, if the job stressors are
      existent in the job environment and the individuals cannot eradicate them, they
      will cause burnout outbreak. 

PMID- 24463595
TI  - Determinants and benefits of physical activity maintenance in hospital employees.
AB  - This study investigated whether the positive behavioral and anthropometric
      outcomes of a pedometer-based physical activity 8-week challenge were maintained
      6 months after the end of the program. It further investigated the motivational
      profile of those who maintained their physical activity levels in the months
      following the end of the program and of those who did not. Hospital employees
      from a university-affiliated multisite health care center in Canada participated
      using a questionnaire. Of the 235 participants who completed the 8-week
      challenge, 157 questionnaires were returned 6 months later. Paired-samples t
      tests were conducted between the baseline and follow-up scores as well as between
      the postprogram and follow-up scores to detect significant differences between
      the measurement points. This study shows that the pedometer-based physical
      activity helped hospital employees maintain a high level of physical activity as
      well as maintain a healthy body mass index after 6 months. The results
      demonstrated that during maintenance the high physical activity group obtained
      higher scores for identified regulation and intrinsic regulation compared with
      the other groups. The results of the study revealed that identified and intrinsic
      regulations are important contributors to maintaining physical activity among
      hospital employees. 

PMID- 24463596
TI  - International classification of diseases, 10th revision training: what coders are
      saying.
AB  - On September 30, 2014, the US health care system will assign the last
      International Classification of Diseases, Ninth Revision, Clinical Modification
      code. The new system, International Classification of Diseases, 10th Revision,
      Clinical Modification/Procedure Coding System, will become effective on October
      1, 2014. A 3-question prepresentation and postpresentation survey was completed
      by attendants at 11 workshops on the new system; this article discusses the
      results of the surveys, revealing what coders and billing staff are saying about
      the new International Classification of Diseases, 10th Revision system. 

PMID- 24463597
TI  - Effect of coronary artery calcium score on the reduction of global cardiovascular
      risk.
AB  - INTRODUCTION: There are no studies evaluating an association between different
      coronary artery calcium scores (CACS) and reduction of traditional cardiovascular
      risk. OBJECTIVES: The aim of the study was to evaluate the effect of coronary
      calcium scoring on the reduction of global cardiovascular risk. PATIENTS AND
      METHODS: This was a prospective single-center study including 180 subjects (mean
      age, 58.8 years). Calcifications on computed tomography were calculated by 2
      experts using the Agatston scale. Selected cardiovascular risk factors and
      medical procedures used in subjects were analyzed. RESULTS: Invasive coronary
      angiography was performed in 60 patients (33.2%). It did not show significant
      coronary lesions in 26 patients (43.3%), while in the other 26 patients (43.3%),
      coronary angioplasty (stent implantation, balloon angioplasty) was performed.
      Eight subjects (13.3%) were referred for coronary artery bypass grafting (CABG),
      and the procedure was performed only in patients with a CACS of 400 AU and
      higher. Angioplasty was performed 10 times more often in these patients compared
      with patients with a CACS of 1 to 399 AU. A significant correlation between the
      CACS and cardiovascular risk was observed in relation to age, weight, and
      systolic and diastolic blood pressure. CONCLUSIONS: Coronary calcium scoring
      allows to identify patients requiring invasive coronary angioplasty, or, in some
      cases, CABG, with greater precision. This can strengthen the role of the CACS as
      a complement to a classic evaluation of cardiovascular risk factors.

PMID- 24463598
TI  - Thrombosis and thromboembolic complications in fontan patients: a literature
      review.
AB  - Hemodynamic fluctuations and thromboembolic complications are significant areas
      of concern during the postoperative management of patients with univentricular
      hearts. The objective of this study is to review the incidence and risk factors
      associated with thrombosis and thromboembolic complications following total
      cavopulmonary anastomosis, the third stage of the palliative surgical procedure.
      A literature search of published evidence was conducted on OvidSP MEDLINE(R) and
      Embase followed by paired title, abstract, and full-text screening based on
      specific inclusion criteria. High risks of thromboembolic outcomes were
      identified across studies, with variable incidences between 3% and 20%, high
      mortality rates up to 38%, and an inverse relationship with prophylaxis treatment
      administration. Several risk factors for thrombotic complications, including
      chronic systemic venous hypertension, protein-losing enteropathy, passive blood
      flow, atrial arrhythmias, conduit stenosis, prosthetic material use, coagulation
      factor abnormalities, and several patient characteristics were identified. Based
      on these findings, a prophylactic anticoagulation algorithm has been proposed.

PMID- 24463599
TI  - Thrombophilic mutations and polymorphisms, alone or in combination, and recurrent
      spontaneous abortion.
AB  - Generally, recurrent spontaneous abortions (RSAs) have no identifiable cause;
      yet, vascular alterations during pregnancy may be associated with pregnancy loss.
      Therefore, we evaluated the association between thrombophilic mutations and RSAs.
      This case-control study was conducted in 112 patients who had RSAs and 98 health
      control women. Genomic DNA was extracted from whole blood, and polymorphism
      genotyping was conducted using polymerase chain reaction. The following 6 genetic
      variants were analyzed: factor V Leiden, prothrombin mutation,
      methylenetetrahydrofolate reductase C677T and A1298C, plasminogen activator
      inhibitor type 1 (4G>5G), and factor XIII G103T (V34L). No correlations were
      found in any of the investigated polymorphisms. Moreover, 35.0% of cases and
      25.5% of controls had at least 2 mutations in combination, and 4.8% of cases and
      5.1% of controls had 3, but these combinations were not associated with
      additional risk. In conclusion, we found no association between the polymorphisms
      studied and the occurrence of RSAs. 

PMID- 24463600
TI  - Is there a correlation between coronary artery ectasia and neutrophil-lymphocyte
      ratio?
AB  - We aimed to investigate the association between the neutrophil-lymphocyte ratio
      (NLR) and coronary artery ectasia (CAE). The study included 198 patients who had
      undergone coronary angiography for suspected coronary artery disease (CAD). The
      patients were divided into the following 4 groups: group 1, 44 patients with
      normal coronary arteries; group 2, 61 patients with CAD; group 3, 40 patients
      with isolated CAE; and group 4, 53 patients with CAE coexisting with CAD.
      Neutrophil-lymphocyte ratio was significantly lower in group 1 than the other
      groups and significantly higher in group 4. Patients in group 1 had significantly
      lower neutrophil counts and significantly higher lymphocyte counts than the
      patients in group 4. The isolated CAE and CAD groups were similar in terms of
      NLR, neutrophil count, and lymphocyte count. In addition, we found significant
      positive correlations between presence of ectasia, number of ectatic vessels, and
      NLR. Our findings provide additional evidence for the role of NLR in CAE. 

PMID- 24463601
TI  - Ventricular structure, function, and focal fibrosis in anabolic steroid users: a
      CMR study.
AB  - PURPOSE: Anabolic steroid (AS) misuse is widespread amongst recreational
      bodybuilders; however, their effects on the cardiovascular system are uncertain.
      Our aim was to document the impact of AS use on cardiac structure, function and
      the presence of focal fibrosis using the gold standard cardiovascular magnetic
      resonance imaging (CMR). METHODS: A cross-sectional cohort design was utilised
      with 21 strength-trained participants who underwent CMR imaging of the heart and
      speckle-tracking echocardiography. Thirteen participants (30 +/- 5 years) taking
      AS for at least 2 years and currently on a "using"-cycle were compared with age
      and training-matched controls (n = 8; 29 +/- 6 years) who self-reported never
      having taken AS (NAS). RESULTS: AS users had higher absolute left ventricular
      (LV) mass (220 +/- 45 g) compared to NAS (163 +/- 27 g; p < 0.05) but this
      difference was removed when indexed to fat-free mass. AS had a reduced right
      ventricular (RV) ejection fraction (AS 51 +/- 4 % vs. NAS 59 +/- 5 %; p < 0.05)
      and a significantly lower left ventricular E':A' myocardial tissue velocity ratio
      [AS 0.99(0.54) vs. NAS 1.78(0.46) p < 0.05] predominantly due to greater tissue
      velocities with atrial contraction. Peak LV longitudinal strain was lower in AS
      users (AS -14.2 +/- 2.7 % vs. NAS -16.6 +/- 1.9 %; p < 0.05). There was no
      evidence of focal fibrosis in any participant. CONCLUSIONS: AS use was associated
      with significant LV hypertrophy, albeit in-line with greater fat-free mass,
      reduced LV strain, diastolic function, and reduced RV ejection fraction in male
      bodybuilders. There was, however, no evidence of focal fibrosis in any AS user.

PMID- 24463602
TI  - Associations of objectively measured sedentary behavior, light activity, and
      markers of cardiometabolic health in young women.
AB  - PURPOSE: To investigate the associations among objectively measured sedentary
      behavior, light physical activity, and markers of cardiometabolic health in young
      women. METHODS: Cardiovascular disease risk factors, homeostasis model assessment
      for insulin resistance (HOMA-IR), lipid accumulation product, and inflammatory
      markers were measured in 50 young, adult women. Accelerometers were worn over 7
      days to assess sedentary time (<150 counts min(-1)), light physical activity (150
      2,689 counts min(-1)), and moderate-to-vigorous physical activity (MVPA; >=2,690
      counts min(-1)). Multivariate regression examined independent associations of
      sedentary behavior and light physical activity with cardiometabolic health.
      Covariates included MVPA, cardiorespiratory fitness (VO2peak) and body mass, and
      body composition. RESULTS: Sedentary behavior was associated with triglycerides
      (p = 0.03) and lipid accumulation product (p = 0.02) independent of MVPA. These
      associations were attenuated by VO2peak and body mass or body composition (p >=
      0.05). Light physical activity was independently associated with triglycerides
      and lipid accumulation product after adjustment for all covariates (p < 0.05).
      The association between light physical activity and HOMA-IR was independent of
      MVPA (p = 0.02) but was attenuated by VO2peak and body mass or body composition
      (p > 0.05). CONCLUSIONS: Sedentary behavior and light physical activity were
      independently associated with markers of cardiometabolic health in young, adult
      women. Our data suggest that VO2peak and body composition may be important
      mediators of these associations. Decreasing sedentary behavior and increasing
      light physical activity may be important for maintaining cardiometabolic health
      in young, adult women.

PMID- 24463603
TI  - Blood pressure regulation XI: overview and future research directions.
AB  - While the importance of regulating arterial blood pressure within a 'normal'
      range is widely appreciated, the definition of 'normal' and the means by which
      humans and other species regulate blood pressure under various conditions remain
      hotly debated. The effects of diverse physiological, pathological and
      environmental challenges on blood pressure and the mechanisms that attempt to
      maintain it at an optimal level are reviewed and critically analyzed in a series
      of articles published in this themed issue of the European Journal of Applied
      Physiology. We summarize here the major points made in these reviews, with
      emphasis on unifying concepts of regulatory mechanisms and future directions for
      research. 

PMID- 24463604
TI  - Gold-catalyzed intermolecular oxidation of chiral homopropargyl sulfonamides: a
      reliable access to enantioenriched pyrrolidin-3-ones.
AB  - A gold-catalyzed intermolecular oxidation of chiral homopropargyl sulfonamides
      has been developed, which provides a reliable access to synthetically useful
      chiral pyrrolidin-3-ones with excellent ee, by combining the chiral tert
      butylsulfinimine chemistry and gold catalysis. This methodology has also been
      used in the facile synthesis of natural product (-)-irniine. The use of readily
      available starting materials, a broad substrate scope, a simple procedure and the
      mild nature of this reaction render it a viable alternative for the synthesis of
      enantioenriched pyrrolidin-3-ones. 

PMID- 24463605
TI  - In vivo transcriptional governance of hair follicle stem cells by canonical Wnt
      regulators.
AB  - Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling.
      Here, we unfold genome-wide transcriptional and chromatin landscapes of beta
      catenin-TCF3/4-TLE circuitry, and genetically dissect their biological roles
      within the native HFSC niche. We show that during HFSC quiescence, TCF3, TCF4 and
      TLE (Groucho) bind coordinately and transcriptionally repress Wnt target genes.
      We also show that beta-catenin is dispensable for HFSC viability, and if TCF3/4
      levels are sufficiently reduced, it is dispensable for proliferation. However,
      beta-catenin is essential to activate genes that launch hair follicle fate and
      suppress sebocyte fate determination. TCF3/4 deficiency mimics Wnt-beta-catenin
      dependent activation of these hair follicle fate targets; TCF3 overexpression
      parallels their TLE4-dependent suppression. Our studies unveil TCF3/4-TLE histone
      deacetylases as a repressive rheostat, whose action can be relieved by Wnt-beta
      catenin signalling. When TCF3/4 and TLE levels are high, HFSCs can maintain
      stemness, but remain quiescent. When these levels drop or when Wnt-beta-catenin
      levels rise, this balance is shifted and hair regeneration initiates. 

PMID- 24463607
TI  - Potential linkages between mineral magnetic measurements and urban roadside soil
      pollution (part 2).
AB  - Use of mineral magnetic concentration parameters (chiLF, chiARM and SIRM) as a
      potential pollution proxy for soil samples collected from Wolverhampton (UK) is
      explored. Comparison of soil-related analytical data by correlation analyses
      between each magnetic parameter and individual geochemical classes (i.e. Fe, Pb,
      Ni, Zn, Cd), are reported. chiLF, chiARM and SIRM parameters reveal significant
      (p < 0.001 n = 60), strong (r = 0.632-0.797), associations with Fe, Cu, Zn and
      Pb. Inter-geochemical correlations suggest anthropogenic influences, which is
      supported by low chiFD% measurements that infer an influence of multi-domain
      mineralogy are indicative of anthropogenic combustion processes. Results indicate
      mineral magnetic measurements could potentially be used as a geochemical
      indicator for soils in certain environments and/or specific settings that are
      appropriate for monitoring techniques. The mineral magnetic technique offers a
      simple, reliable, rapid, sensitive, inexpensive and non-destructive approach that
      could be a valuable pollution proxy for soil contamination studies. 

PMID- 24463606
TI  - A polarized Ca2+, diacylglycerol and STIM1 signalling system regulates directed
      cell migration.
AB  - Ca(2+) signals control cell migration by regulating forward movement and cell
      adhesion. However, it is not well understood how Ca(2+)-regulatory proteins and
      second messengers are spatially organized in migrating cells. Here we show that
      receptor tyrosine kinase and phospholipase C signalling are restricted to the
      front of migrating endothelial leader cells, triggering local Ca(2+) pulses,
      local depletion of Ca(2+) in the endoplasmic reticulum and local activation of
      STIM1, supporting pulsatile front retraction and adhesion. At the same time, the
      mediator of store-operated Ca(2+) influx, STIM1, is transported by microtubule
      plus ends to the front. Furthermore, higher Ca(2+) pump rates in the front
      relative to the back of the plasma membrane enable effective local Ca(2+)
      signalling by locally decreasing basal Ca(2+). Finally, polarized phospholipase C
      signalling generates a diacylglycerol gradient towards the front that promotes
      persistent forward migration. Thus, cells employ an integrated Ca(2+) control
      system with polarized Ca(2+) signalling proteins and second messengers to
      synergistically promote directed cell migration. 

PMID- 24463612
TI  - Career transitions.

PMID- 24463610
TI  - Metabolic engineering of Nicotiana benthamiana for the increased production of
      taxadiene.
AB  - We report the production of taxadiene by transformation of N. benthamiana with a
      taxadiene synthase gene. The production was significantly increased by an
      elicitor treatment or metabolic pathway shunting. Paclitaxel (Taxol((r))) was
      first isolated from the bark of the pacific yew tree as an anticancer agent and
      has been used extensively to treat various types of cancer. Taxadiene, the first
      committed product of paclitaxel synthesis is cyclized from geranylgeranyl
      diphosphate (GGPP), and further complex hydroxylation and acylation processes of
      the unique taxane core skeleton produce paclitaxel. To accomplish de novo
      production of taxadiene, we transformed Nicotiana benthamiana with a taxadiene
      synthase (TS) gene. The introduced TS gene under the transcriptional control of
      the CaMV 35S promoter was constitutively expressed in N. benthamiana, and the de
      novo production of taxadiene was confirmed by mass spectroscopy profiling.
      Transformed N. benthamiana homozygous lines produced 11-27 MUg taxadiene/g of dry
      weight. The highest taxadiene production line TSS-8 was further treated with an
      elicitor, methyl jasmonate, and metabolic pathway shunting by suppression of the
      phytoene synthase gene expression which resulted in accumulation of increased
      taxadiene accumulation by 1.4- or 1.9-fold, respectively. In summary, we report
      that the production of taxadiene in N. benthamiana was possible by the ectopic
      expression of the TS gene, and higher accumulation of taxadiene could be achieved
      by elicitor treatment or metabolic pathway shunting of the terpenoid pathway.

PMID- 24463611
TI  - Super-luminescent jet light generated by femtosecond laser pulses.
AB  - Phenomena of nonlinear light-matter interaction that occur during the propagation
      of intense ultrashort laser pulses in continuous media have been extensively
      studied in ultrafast optical science. In this vibrant research field, conversion
      of the input laser beam into optical filament(s) is commonly encountered. Here,
      we demonstrate generation of distinctive single or double super-luminescent
      optical jet beams as a result of strong spatial-temporal nonlinear interaction
      between focused 50 fs millijoule laser pulses and their induced micro air plasma.
      Such jet-like optical beams, being slightly divergent and coexisting with
      severely distorted conical emission of colored speckles, are largely different
      from optical filaments, and obtainable when the focal lens of proper f-number is
      slightly tilted or shifted. Once being collimated, the jet beams can propagate
      over a long distance in air. These beams not only reveal a potentially useful
      approach to coherent optical wave generation, but also may find applications in
      remote sensing.

PMID- 24463613
TI  - Motivational interviewing: a journey to improve health.

PMID- 24463614
TI  - Identification of differently expressed genes and small molecule drugs for
      Tetralogy of Fallot by bioinformatics strategy.
AB  - This study aimed to screen out differentially expressed genes (DEGs) and explore
      small molecule drugs for Tetralogy of Fallot (TOF). The gene expression profile
      of TOF GSE26125 was downloaded from the Gene Expression Omnibus database,
      including 16 idiopathic TOF samples and five healthy controls. The DEGs were
      identified by the Limma package in R language and underwent functional enrichment
      analysis via Database for Annotation, Visualization and Integrated Discovery
      tools. A protein-protein interaction (PPI) network of DEGs was then constructed
      and the significant clusters were selected for functional analysis. In addition,
      the DEGs were mapped to the connectivity map (CMap) database to identify
      potential small-molecule drugs. As a result, a total of 499 DEGs were selected
      between TOF and healthy controls. Meanwhile, the functional changes of DEGs
      related to TOF were mainly associated with cellular respiration and energy
      metabolism. Furthermore, in the PPI network, two clusters were identified via
      cluster 1 analysis. And only cluster 1 was significantly enriched into gene
      ontology terms, including respiratory chain, electron transport chain, and
      oxidation reduction. The hub gene of cluster 1 was NDUFAB1. Additionally, small
      molecules, such as harmine, solanine, and testosterone, may have the potential to
      repair the disordered metabolic pathways of TOF.

PMID- 24463615
TI  - The quality of life of Brazilian patients in palliative care: validation of the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 15 PAL (EORTC QLQ-C15-PAL).
AB  - PURPOSE: The purpose of this study was to validate the Brazilian version of the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 15 PAL (EORTC QLQ-C15-PAL) to be used in patients with cancer
      in palliative care. METHODS: One hundred four outpatients with advanced cancer
      were recruited in Hospital das Clinicas--University of Sao Paulo, Brazil.
      RESULTS: The confirmatory factor analysis confirmed that Cronbach-alpha is >=0.7
      except for fatigue (alpha = 0.58). Convergent validity was shown by the
      correlation observed between the EORTC QLQ-C15-PAL dimensions with the EORTC QLQ
      C30, Brief Pain Inventory, and Beck Depression Inventory. The EORTC QLQ-C15-PAL
      detected significant differences in the performance status, supporting known
      group validity. CONCLUSIONS: Our data show that EORTC QLQ-C15-PAL is a brief,
      useful, and valid tool for assessing the quality of life of Brazilian patients in
      palliative care.

PMID- 24463616
TI  - Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic
      review and meta-analysis of prospective randomised trials.
AB  - PURPOSE: Hand-foot syndrome (HSF) is a distinctive adverse event relatively
      frequent to some chemotherapeutic agents as capecitabine, pegylated liposomal
      doxorubicin, sorafenib and other tyrosine-kinase inhibitors. Since the prevention
      of HFS would be crucial to avoid treatment interruptions and delays, many studies
      have been conducted with this purpose. METHODS: The aim of this systematic review
      and meta-analysis was to analyze the clinical efficacy of prevention strategies
      for HFS, through a wide search of electronic databases as well as congress
      abstracts. The endpoints evaluated were the dichotomic data for mild (Grade 1),
      moderate to severe (Grades 2 to 3) and all-grade HFS. Meta-analysis was
      calculated through RevMan v5.1 software. RESULTS: Amongst 295 studies identified,
      only ten met the inclusion criteria. Celecoxib prevented both moderate to severe
      (odds ratio [OR] 0.39, 95 % confidence interval [CI] 0.20-0.73, P = 0.003) and
      all-grade HFS (OR 0.47, 95 % CI 0.29-0.78, P = 0.003), whereas pyridoxine and
      topical urea/lactic acid formulations failed to prove efficacy. There were no
      proven benefits in mild HFS. The use of topical antiperspirant has not been shown
      to improve results, according to a single trial. CONCLUSIONS: From all available
      possibilities for the prevention of HFS, celecoxib appears to be the most
      promising, with statistically significant results. Larger, multicentric studies
      are required to reinforce this finding.

PMID- 24463617
TI  - A comparison of the compositional differences between humic fractions isolated by
      the IHSS and exhaustive extraction procedures.
AB  - Humic substances (HSs), consisting, on the basis of solubilities in aqueous acid
      and basic media, of humic acids (HAs), fulvic acids (FAs), and humin (Hu), are
      the major components of soil organic matter (SOM). Most studies of soil/natural
      organic matter (SOM/NOM) have been carried out on extracts of soils in dilute
      sodium hydroxide solutions, the solvent used to extract the Standards of the
      International Humic Substances Society (IHSS). However, Hu, the major component
      in the classical definition of HSs, is insoluble in aqueous base and is not
      isolated by the traditional IHSS method. Recently, a sequential exhaustive
      extraction (SEE) process has been shown to be capable of isolating and separating
      the major components of the classically defined HSs from the soils of the
      temperate and tropical regions. The SEE system was used in the present study to
      isolate the HA/FA and Hu fractions from a subtropical volcanic Taiwanese soil.
      Chemical and compositional properties of these extracts were then compared with
      similarly obtained isolates from soils from the different climatic regions.
      Increases in the aliphatic relative to aromatic carbon contents were observed for
      both the HA and FA fractions when the pH values of the extraction media were
      increased. HAs and FAs isolated using the SEE method have spectroscopic profiles
      similar to those from the IHSS isolate; however, the cumulative extraction
      efficiency (%) of the SEE method (65 %) for the volcanic soil was much higher
      than for the traditional IHSS method (33 %). When the residual volcanic soil,
      following extractions once, three, and eight times with 0.1 M NaOH were then
      extracted with dimethyl sulphoxide (DMSO) plus concentrated sulphuric acid (the
      final solvent in the SEE sequence) it was seen that the content of crystalline
      polymethylene hydrocarbon (33 ppm (13)C-NMR resonance in the Hu (or DMSO/acid))
      extract increased relative to the amorphous methylene (30 ppm). That highlights
      the difficulty in dissolving the more highly ordered hydrocarbon structures that
      would be expected to have closer associations with the mineral colloids. Although
      the SEE procedure isolated all of the HAs and FAs from the Yangmingshan soil,
      extractability of the Hu from the volcanic soil in the DMSO/acid solvent was low
      (21 %), and contrasted with the much higher yields from temperate and tropical
      regions. The decreased Hu extraction may arise from its associations with the
      extensive iron and aluminium hydroxide mineral colloids in the soil. The Hu from
      this sub-tropical soil was different from the Hus isolated from other soil types,
      indicating the need to isolate and characterise these recalcitrant organic
      material in order to understand the organic carbon components in soils in greater
      detail. Such results would indicate that more attention should be given to
      mineral colloids in soils, and to the organo/mineral associations that will have
      an important role in the stabilities of OM in the soil environment.

PMID- 24463618
TI  - Selective aggressiveness in European free-tailed bats (Tadarida teniotis):
      influence of familiarity, age and sex.
AB  - Bats are highly social mammals that often form large groups and represent good
      models to test the role played by individual status in shaping social
      relationships. Social cohesion relies on the ability of group and individual
      recognition, which is mediated by a range of sensorial cues. In this study, we
      selected the European free-tailed bat Tadarida teniotis as a model species to
      test the effects of familiarity, sex and age on aggressiveness and mutual
      tolerance. We hypothesize that T. teniotis is able to recognize group members and
      exhibit selective aggressiveness, and thus we predict fewer aggressive events and
      more amicable encounters between colony mates than between strangers. As female
      bats are generally more sociable and perform prolonged parental care to juveniles
      even after weaning, we hypothesize that sex and age of bats have significant
      influences on aggressive behaviours and thus predict that females will perform
      more amicable behaviours than males and that adults of both sexes will be less
      aggressive towards juveniles. Our results confirm that T. teniotis is able to
      discriminate between familiar and stranger individuals, showing higher rates of
      aggressive behaviours towards the latter. Females are more prone to exhibit
      amicable behaviours, particularly during same-sex interactions, while males show
      higher level of aggressiveness. Juveniles are subjected to fewer aggressive
      behaviours by adults of both sexes. Familiarity appears crucial for T. teniotis
      in determining the degree of aggressiveness during social interactions but the
      rate of aggressive events is also influenced by intrinsic individual factors such
      as sex and age.

PMID- 24463619
TI  - A time-compressed simulated geomagnetic storm influences the nest-exiting flight
      angles of the stingless bee Tetragonisca angustula.
AB  - Insects have been used as models for understanding animal orientation. It is well
      accepted that social insects such as honeybees and ants use different natural
      cues in their orientation mechanism. A magnetic sensitivity was suggested for the
      stingless bee Schwarziana quadripunctata, based on the observation of a
      surprising effect of a geomagnetic storm on the nest-exiting flight angles.
      Stimulated by this result, in this paper, the effects of a time-compressed
      simulated geomagnetic storm (TC-SGS) on the nest-exiting flight angles of another
      stingless bee, Tetragonisca angustula, are presented. Under an applied SGS,
      either on the horizontal or vertical component of the geomagnetic field, both
      nest-exiting flight angles, dip and azimuth, are statistically different from
      those under geomagnetic conditions. The angular dependence of ferromagnetic
      resonance (FMR) spectra of whole stingless bees shows the presence of organized
      magnetic nanoparticles in their bodies, which indicates this material as a
      possible magnetic detector.

PMID- 24463620
TI  - Monogamy in large bee societies: a stingless paradox.
AB  - High genetic diversity is important for the functioning of large insect
      societies. Across the social Hymenoptera (ants, bees, and wasps), species with
      the largest colonies tend to have a high colony-level genetic diversity resulting
      from multiple queens (polygyny) or queens that mate with multiple males
      (polyandry). Here we studied the genetic structure of Trigona spinipes, a
      stingless bee species with colonies an order of magnitude larger than those of
      polyandrous honeybees. Genotypes of adult workers and pupae from 43 nests
      distributed across three Brazilian biomes showed that T. spinipes colonies are
      usually headed by one singly mated queen. Apart from revealing a notable
      exception from the general incidence of high genetic diversity in large insect
      societies, our results reinforce previous findings suggesting the absence of
      polyandry in stingless bees and provide evidence against the sperm limitation
      hypothesis for the evolution of polyandry. Stingless bee species with large
      colonies, such as T. spinipes, thus seem promising study models to unravel
      alternative mechanisms to increase genetic diversity within colonies or
      understand the adaptive value of low genetic diversity in large insect societies.

PMID- 24463621
TI  - Long-term treatment with naproxcinod significantly improves skeletal and cardiac
      disease phenotype in the mdx mouse model of dystrophy.
AB  - In Duchenne muscular dystrophy (DMD) patients and the mouse model of DMD, mdx,
      dystrophin deficiency causes a decrease and mislocalization of muscle-specific
      neuronal nitric oxide synthase (nNOSMU), leading to functional impairments.
      Previous studies have shown that nitric oxide (NO) donation associated with anti
      inflammatory action has beneficial effects in dystrophic mouse models. In this
      study, we have systematically investigated the effects of naproxcinod, an NO
      donating naproxen derivative, on the skeletal and cardiac disease phenotype in
      mdx mice. Four-week-old mdx and C57BL/10 mice were treated with four different
      concentrations (0, 10, 21 and 41 mg/kg) of naproxcinod and 0.9 mg/kg of
      prednisolone in their food for 9 months. All mice were subjected to twice-weekly
      treadmill sessions, and functional and behavioral parameters were measured at 3,
      6 and 9 months of treatment. In addition, we evaluated in vitro force
      contraction, optical imaging of inflammation, echocardiography and blood pressure
      (BP) at the 9-month endpoint prior to sacrifice. We found that naproxcinod
      treatment at 21 mg/kg resulted in significant improvement in hindlimb grip
      strength and a 30% decrease in inflammation in the fore- and hindlimbs of mdx
      mice. Furthermore, we found significant improvement in heart function, as
      evidenced by improved fraction shortening, ejection fraction and systolic BP. In
      addition, the long-term detrimental effects of prednisolone typically seen in mdx
      skeletal and heart function were not observed at the effective dose of
      naproxcinod. In conclusion, our results indicate that naproxcinod has significant
      potential as a safe therapeutic option for the treatment of muscular dystrophies.

PMID- 24463622
TI  - CNS expression of murine fragile X protein (FMRP) as a function of CGG-repeat
      size.
AB  - Large expansions of a CGG-repeat element (>200 repeats; full mutation) in the
      fragile X mental retardation 1 (FMR1) gene cause fragile X syndrome (FXS), the
      leading single-gene form of intellectual disability and of autism spectrum
      disorder. Smaller expansions (55-200 CGG repeats; premutation) result in the
      neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS).
      Whereas FXS is caused by gene silencing and insufficient FMR1 protein (FMRP),
      FXTAS is thought to be caused by 'toxicity' of expanded-CGG-repeat mRNA. However,
      as FMRP expression levels decrease with increasing CGG-repeat length, lowered
      protein may contribute to premutation-associated clinical involvement. To address
      this issue, we measured brain Fmr1 mRNA and FMRP levels as a function of CGG
      repeat length in a congenic (CGG-repeat knock-in) mouse model using 57 wild-type
      and 97 expanded-CGG-repeat mice carrying up to ~250 CGG repeats. While Fmr1
      message levels increased with repeat length, FMRP levels trended downward over
      the same range, subject to significant inter-subject variation. Human comparisons
      of protein levels in the frontal cortex of 7 normal and 17 FXTAS individuals
      revealed that the mild FMRP decrease in mice mirrored the more limited data for
      FMRP expression in the human samples. In addition, FMRP expression levels varied
      in a subset of mice across the cerebellum, frontal cortex, and hippocampus, as
      well as at different ages. These results provide a foundation for understanding
      both the CGG-repeat-dependence of FMRP expression and for interpreting clinical
      phenotypes in premutation carriers in terms of the balance between elevated mRNA
      and lowered FMRP expression levels.

PMID- 24463624
TI  - Cerebral microbleeding in varicella-zoster viral meningitis: an early sign of
      vasculopathy?

PMID- 24463623
TI  - Therapeutic benefit of lentiviral-mediated neonatal intracerebral gene therapy in
      a mouse model of globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD) is an inherited lysosomal storage disease
      caused by beta-galactocerebrosidase (GALC) deficiency. Gene therapy (GT) should
      provide rapid, extensive and lifetime GALC supply in central nervous system (CNS)
      tissues to prevent or halt irreversible neurologic progression. Here we used a
      lentiviral vector (LV) to transfer a functional GALC gene in the brain of
      Twitcher mice, a severe GLD model. A single injection of LV.GALC in the external
      capsule of Twitcher neonates resulted in robust transduction of neural cells with
      minimal and transient activation of inflammatory and immune response.
      Importantly, we documented a proficient transduction of proliferating and post
      mitotic oligodendroglia, a relevant target cell type in GLD. GALC activity (30
      50% of physiological levels) was restored in the whole CNS of treated mice as
      early as 8 days post-injection. The early and stable enzymatic supply ensured
      partial clearance of storage and reduction of psychosine levels, translating in
      amelioration of histopathology and enhanced lifespan. At 6 months post-injection
      in non-affected mice, LV genome persisted exclusively in the injected region,
      where transduced cells overexpressed GALC. Integration site analysis in
      transduced brain tissues showed no aberrant clonal expansion and preferential
      targeting of neural-specific genes. This study establishes neonatal LV-mediated
      intracerebral GT as a rapid, effective and safe therapeutic intervention to
      correct CNS pathology in GLD and provides a strong rationale for its application
      in this and similar leukodystrophies, alone or in combination with therapies
      targeting the somatic pathology, with the final aim of providing an effective and
      timely treatment of these global disorders.

PMID- 24463625
TI  - Early pediatric antiepileptic drug nonadherence is related to lower long-term
      seizure freedom.
AB  - OBJECTIVE: To examine the relationship between previously identified nonadherence
      trajectories during the first 6 months of antiepileptic drug (AED) therapy and
      long-term seizure-free rates (defined as >=1 year of seizure freedom at the 4
      years postdiagnosis milestone) in a cohort of children with newly diagnosed
      epilepsy. METHODS: A prospective longitudinal observational study of AED
      adherence and seizure freedom in a consecutive cohort of 124 children (ages 2-12
      years) with newly diagnosed epilepsy was conducted. The association between
      previously identified AED adherence trajectories (i.e., near-perfect adherence
      [e.g., average adherence = 96.8%] vs nonadherent) and seizure freedom for >=1
      year at the 4 years postdiagnosis milestone was determined. RESULTS: Children who
      exhibited nonadherence to AED therapy in the first 6 months of treatment were
      3.24 times more likely not to have achieved >=1 year of seizure freedom at the 4
      years postdiagnosis milestone compared to children in the near-perfect adherence
      group (chi2 = 5.13; p = 0.02). Specifically, at the 4 years postdiagnosis
      milestone, only 12% of children in the near-perfect adherence group were
      continuing to experience seizures compared to 31% of children in the nonadherent
      group. CONCLUSIONS: Children with epilepsy who achieved near-perfect adherence
      during the first 6 months of therapy experienced a higher rate of seizure freedom
      4 years postdiagnosis compared with those children who demonstrated early
      nonadherence. This suggests that adherence intervention early in the course of
      treatment could play a role in improving long-term seizure freedom rates in
      children with epilepsy.

PMID- 24463626
TI  - Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification
      in Japan.
AB  - OBJECTIVE: To investigate the clinical, genetic, and neuroradiologic
      presentations of idiopathic basal ganglia calcification (IBGC) in a nationwide
      study in Japan. METHODS: We documented clinical and neuroimaging data of a total
      of 69 subjects including 23 subjects from 10 families and 46 subjects in sporadic
      cases of IBGC in Japan. Mutational analysis of SLC20A2 was performed. RESULTS:
      Six new mutations in SLC20A2 were found in patients with IBGC: 4 missense
      mutations, 1 nonsense mutation, and 1 frameshift mutation. Four of them were
      familial cases and 2 were sporadic cases in our survey. The frequency of families
      with mutations in SLC20A2 in Japan was 50%, which was as high as in a previous
      report on other regions. The clinical features varied widely among the patients
      with SLC20A2 mutations. However, 2 distinct families have the same mutation of
      S637R in SLC20A2 and they have similar characteristics in the clinical course,
      symptoms, neurologic findings, and neuroimaging. In our study, all the patients
      with SLC20A2 mutations showed calcification. In familial cases, there were
      symptomatic and asymptomatic patients in the same family. CONCLUSION: SLC20A2
      mutations are a major cause of familial IBGC in Japan. The members in the
      families with the same mutation had similar patterns of calcification in the
      brain and the affected members showed similar clinical manifestations.

PMID- 24463628
TI  - Antiepileptic drug nonadherence in children with epilepsy: outcomes and potential
      intervention.

PMID- 24463629
TI  - The pill times 2: what every woman with multiple sclerosis should know.

PMID- 24463630
TI  - Pregnancy outcomes in the clinical development program of fingolimod in multiple
      sclerosis.
AB  - OBJECTIVE: To report outcomes of pregnancies that occurred during the fingolimod
      clinical development program. METHODS: Pregnancy outcomes from phase II, phase
      III, and phase IV clinical studies (with optional extensions) were reported by
      clinical trial investigators. Fingolimod exposure in utero was defined as
      fingolimod treatment at the time of conception or in the 6 weeks before
      conception. RESULTS: As of October 31, 2011, 89 pregnancies were reported in
      completed or ongoing clinical studies, with 74 in fingolimod treatment arms. Of
      66 pregnancies with in utero exposure to fingolimod, there were 28 live births, 9
      spontaneous abortions, 24 elective abortions, 4 ongoing pregnancies, and 1
      pregnancy with an unknown outcome (patient lost to follow-up). Two infants were
      born with malformations: 1 with congenital unilateral posteromedial bowing of the
      tibia and 1 with acrania. Elective abortions were performed for 1 case each of
      tetralogy of Fallot, spontaneous intrauterine death, and failure of fetal
      development. There were 5 cases (7.6%; 95% confidence interval 3%-17%) of
      abnormal fetal development in the 66 pregnancies that had in utero exposure to
      fingolimod. In all 5 cases, fetal exposure to the drug took place in the first
      trimester of pregnancy. CONCLUSIONS: The number of patients becoming pregnant
      during fingolimod therapy remains small and does not permit firm conclusions to
      be drawn about fetal safety of fingolimod in humans. Given the known risks of
      teratogenicity in animals and the present data, women of childbearing potential
      should use effective contraception during fingolimod therapy and for 2 months
      after discontinuation.

PMID- 24463631
TI  - Large magnetoelectric coupling in Co4Nb2O9.
AB  - Magnetoelectric materials which simultaneously exhibit electric polarization and
      magnetism have attracted more and more attention due to their novel physical
      properties and promising applications for next-generation devices. Exploring new
      materials with outstanding magnetoelectric performance, especially the
      manipulation of magnetization by electric field, is of great importance. Here, we
      demonstrate the cross-coupling between magnetic and electric orders in
      polycrystalline Co4Nb2O9, in which not only magnetic-field-induced electric
      polarization but also electric field control of magnetism is observed. These
      results reveal rich physical phenomenon and potential applications in this
      compound. 

PMID- 24463632
TI  - Blessed alienation: the Christian monastery as a caring and restorative
      environment.
AB  - Being mentally ill is often associated with experiencing alienation from society
      because sensations are not easily shared with others. Modern health care leads us
      to pose many questions. Some sufferers search and find their way to monasteries
      as they did centuries ago. We interviewed six persons staying in a monastery to
      understand the meaning of health and care in a monastic environment in
      contemporary Sweden. We analyzed the transcripts by means of a hermeneutic
      approach and discovered that the helping effect of the monastery was based on its
      contradictory/paradoxical structure that corresponded to the lifeworld of a
      person suffering from mental illness. The monastery was a place where one could
      be different but equal, and simultaneously provided freedom within boundaries,
      calmness and intensity, privacy and relations, demands and confirmation. This
      facilitated experiences of health and wholeness, necessary to manage the
      challenges of recovery. 

PMID- 24463633
TI  - Terms used for people living with HIV in the Democratic Republic of the Congo.
AB  - For this study we conducted in-depth interviews with 29 youth living with HIV
      (YLWH) and key informant interviews with 8 HIV care/support providers. We
      describe terms used to portray people living with HIV (PLWH) in Kinshasa,
      Democratic Republic of the Congo. Labels commonly used, mostly derogatory,
      described PLWH as walking corpses, dangers to others, or people deserving to die
      before others get infected. Blame and other accusations were directed at PLWH
      through anchoring or objectification. Being labeled sometimes made these youth
      suffer in silence, afraid to disclose their status, or avoid performing actions
      in public, preferring to let others do them. YLWH need psychosocial support to
      mitigate the harmful effects of these labels and strengthen their coping skills,
      whereas community, institutional, and national efforts are needed for stigma
      reduction. 

PMID- 24463634
TI  - Strong pulsed excitations using circularly polarized fields for ultra-low field
      NMR.
AB  - A pulse, which is produced by a single coil and thereby has a linear
      polarization, cannot coherently drive nuclear spins if the pulse is stronger than
      the static field B0. The inaccuracy of the pulse, which arises from the failure
      of the rotating wave approximation, has been an obstacle in adopting multiple
      pulse techniques in ultra-low field NMR where B0 is less than a few MUT. Here, we
      show that such a limitation can be overcome by applying pulses of circular
      polarization using two orthogonal coils. The sinusoidal nutation of the nuclear
      spins was experimentally obtained, which indicates that coherent and precise
      controls of the nuclear spins can be achieved with circularly polarized pulses.
      Additional demonstration of the Carl-Purcell-Meiboom-Gill sequence verifies the
      feasibility of adopting multiple pulse sequences to ultra-low field NMR studies. 

PMID- 24463635
TI  - Large-area fabrication of highly reproducible surface enhanced Raman substrate
      via a facile double sided tape-assisted transfer approach using hollow Au-Ag
      alloy nanourchins.
AB  - Ideally, a SERS substrate should possess super signal amplification, high
      uniformity and reproducibility. Up to now, an emphasis on reproducibility and
      uniformity has been crucial to ensure consistent chemical detection sensitivity
      across the surface of a SERS substrate. Here we demonstrate a simple and facile
      double sided tape-assisted transfer method to fabricate surface enhanced Raman
      scattering (SERS) substrates with prominent performance using hollow Au-Ag alloy
      nanourchins (HAAA-NUs). Such a large area, closely-packed flat film of the HAAA
      NUs with a high density of "hot spots" exhibits a high SERS activity and
      reproducibility, simultaneously. The AFM-correlated nano-Raman and the point by
      point scanning of SERS signals verify the excellent spatial uniformity and
      reproducibility with a low relative standard deviation (RSD) less than 15% using
      crystal violet as probe molecule at the concentrations of 1 * 10(-8) M and 1 *
      10(-10) M. The SERS signals of Sudan dye at a 1 * 10(-8) M concentration also
      show high reproducibility with a low RSD of 13.8%. This facile protocol presented
      here could lead to a high quality SERS substrate and open tremendous potential
      for various applications. 

PMID- 24463636
TI  - A visible light responsive rhodium and antimony-codoped SrTiO3 powdered
      photocatalyst loaded with an IrO2 cocatalyst for solar water splitting.
AB  - IrO2-loaded SrTiO3 doped with rhodium and antimony synthesized by a conventional
      solid-state reaction splits water under visible light and simulated sunlight
      irradiation giving 0.1% of the apparent quantum yield at 420 nm. The response
      wavelength up to 500 nm is the longest among achieved photocatalytic water
      splitting with one-step photoexcitation. 

PMID- 24463637
TI  - Sensory uncertainty and stick balancing at the fingertip.
AB  - The effects of sensory input uncertainty, [Formula: see text], on the stability
      of time-delayed human motor control are investigated by calculating the minimum
      stick length, [Formula: see text], that can be stabilized in the inverted
      position for a given time delay, [Formula: see text]. Five control strategies
      often discussed in the context of human motor control are examined: three time
      invariant controllers [proportional-derivative, proportional-derivative
      acceleration (PDA), model predictive (MP) controllers] and two time-varying
      controllers [act-and-wait (AAW) and intermittent predictive controllers]. The
      uncertainties of the sensory input are modeled as a multiplicative term in the
      system output. Estimates based on the variability of neural spike trains and
      neural population responses suggest that [Formula: see text]-13 %. It is found
      that for this range of uncertainty, a tapped delay-line type of MP controller is
      the most robust controller. In particular, this controller can stabilize inverted
      sticks of the length balanced by expert stick balancers (0.25-0.5 m when
      [Formula: see text] s). However, a PDA controller becomes more effective when
      [Formula: see text]. A comparison between [Formula: see text] for human stick
      balancing at the fingertip and balancing on the rubberized surface of a table
      tennis racket suggest that friction likely plays a role in balance control.
      Measurements of [Formula: see text], and a variability of the fluctuations in the
      vertical displacement angle, an estimate of [Formula: see text], may make it
      possible to study the changes in control strategy as motor skill develops.

PMID- 24463638
TI  - Perforated appendicitis: an underappreciated mimic of intussusception on
      ultrasound.
AB  - BACKGROUND: We encountered multiple cases in which the US appearance of ruptured
      appendicitis mimicked intussusception, resulting in diagnostic and therapeutic
      delay and multiple additional imaging studies. OBJECTIVE: To explore the clinical
      and imaging discriminatory features between the conditions. MATERIALS AND
      METHODS: Initial US images in six children (age 16 months to 8 years; 4 boys, 2
      girls) were reviewed independently and by consensus by three pediatric
      radiologists. These findings were compared and correlated with the original
      reports and subsequent US, fluoroscopic, and CT images and reports. RESULTS: All
      initial US studies demonstrated a multiple-ring-like appearance (target sign,
      most apparent on transverse views) with diagnostic consensus supportive of
      intussusception. In three cases, US findings were somewhat discrepant with
      clinical concerns. Subsequently, four of the six children had contrast enemas;
      two were thought to have partial or complete intussusception reduction. Three had
      a repeat US examination, with recognition of the correct diagnosis. None of the
      US examinations demonstrated definite intralesional lymph nodes or mesenteric
      fat, but central echogenicity caused by debris/appendicolith was misinterpreted
      as fat. All showed perilesional hyperechogenicity that, in retrospect,
      represented inflamed fat "walling off" of the perforated appendix. There were
      four CTs, all of which demonstrated a double-ring appearance that correlated with
      the US target appearance, with inner and outer rings representing the dilated
      appendix and walled-off appendiceal rupture, respectively. All six children had
      surgical confirmation of perforated appendicitis. CONCLUSION: Contained
      perforated appendicitis can produce US findings closely mimicking
      intussusception. Clinical correlation and careful multiplanar evaluation should
      allow for sonographic suspicion of perforated appendicitis, which can be
      confirmed on CT if necessary.

PMID- 24463639
TI  - Reproductive factors and the risk of endometrial cancer.
AB  - Endometrial cancer is the most common malignancy of women in developed countries,
      and its incidence is 10 times higher than in developing countries. Endometrial
      cancer is most common in the sixth and the seventh decades of life; thus,
      postmenopausal women have a higher risk of developing the disease compared with
      premenopausal women. The increased incidence and prevalence of endometrial cancer
      can be explained by the increase in life expectancy, increased caloric intake,
      increased obesity rates, and other changes in lifestyle and reproductive factors.
      Among the reproductive factors, the risk of endometrial cancer is positively
      correlated with a younger age at menarche and late age at menopause, infertility,
      null parity, age of the first child, and long-term use of unopposed estrogens for
      hormone replacement therapy. Protection against endometrial cancer has been
      detected with increase parity, the use of combined oral contraceptives, and
      increased age of women at last delivery. The relationship between endometrial
      cancer risk and miscarriage, abortion, ovulation induction drugs and in vitro
      fertilization is still controversial. 

PMID- 24463640
TI  - Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of
      ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to investigate the preoperative
      diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography
      and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One
      hundred sixty patients suspected of having malignant ovarian tumors were included
      in this study. All patients underwent FDG-PET/CT scans before operation, and the
      maximum standardized uptake value (SUVmax) of the primary tumor was measured. We
      evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its
      relationship with histological findings. RESULTS: Postoperative pathological
      diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79
      were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the
      receiver operating characteristic curve analysis, the sensitivity, specificity,
      positive predictive value, and negative predictive value for detecting malignancy
      were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation
      (SUVmax >= 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of
      endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG
      accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous
      adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax
      of these 3 histological types were significantly lower than those of serous and
      endometrioid types. In addition, a positive FDG accumulation was shown in all
      patients with malignant transformation of mature cystic teratoma. Finally, of the
      14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation.
      CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian
      cancer from borderline or benign tumor with a high specificity and positive
      predictive value. However, our data also demonstrated a lower FDG uptake value in
      clear cell or mucinous histological finding, suggesting that SUVmax may vary
      depending on the tumor histological subtype.

PMID- 24463641
TI  - Impact of ascites on the perioperative course of patients with advanced ovarian
      cancer undergoing extensive cytoreduction: results of a study on 119 patients.
AB  - OBJECTIVE: Cytoreductive surgery for epithelial ovarian cancer (EOC) is the
      cornerstone of multimodal therapy and considered as a high-risk surgery because
      of extensive multivisceral procedures. In most patients, ascites is present, but
      its impact on the surgical and clinical outcomes is unclear. METHODS: One hundred
      nineteen patients undergoing surgical cytoreduction because of EOC between 2005
      and 2008 were included. All surgical data and the individual tumor pattern were
      collected systematically based on a validated documentation tool (intraoperative
      mapping of ovarian cancer) during primary surgery. The amount of ascites was
      determined at the time of surgery, and 3 groups were classified (no ascites [NOA,
      n = 56], low amount of ascites [< 500 mL, n = 42], and high amount of ascites
      [HAS > 500 mL, n = 21]). RESULTS: Group NOA compared with HAS showed less
      transfusions of packed red blood cells (median [quartiles], 0 [0-2] vs 0 [0-2] vs
      3 [1-4] U; P < 0.001) and fresh frozen plasma (median [quartiles], 0 [0-2] vs 0
      [0-4] vs 2 [2-6] U; P < 0.001). In addition, in patients with ascites,
      noradrenaline was administered more frequently and in higher doses. The
      postoperative length of stay in the intensive care unit was significantly shorter
      in the NOA versus the group with low amount of ascites and HAS (median
      [quartiles], 1 [0-1] vs 1 [0-2] vs 2 [1-5] days; P < 0.001). The hospital length
      of stay is extended in HAS compared with that in NOA (median [quartiles], 16 [13
      20] vs 17 [14-22] vs 21 [17-41] days; P = 0.004). Postoperative complications
      were increased in patients with ascites at the time of surgery (P = 0.007).
      CONCLUSIONS: The presence of a high amount of ascites at cytoreductive surgery
      because of EOC is associated with higher amounts of blood transfusions, whereas
      the length of hospital stay and the postoperative intensive care unit treatment
      are significantly prolonged compared with those of patients without ascites.

PMID- 24463642
TI  - Clinical analysis of primary primitive neuroectodermal tumors in the female
      genital tract.
AB  - OBJECTIVE: The aim of the study was to investigate the clinical manifestations,
      diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs)
      in the female genital tract. METHODS: From April 2001 to May 2013, the
      clinicopathologic characteristics, treatments, outcomes, and prognosis of 11
      patients with PNET in the female genital tract were analyzed retrospectively at
      our hospital. RESULTS: The location of PNET in the 11 patients presented here
      included vulva (2 patients), cervix (2 patients), uterus and its ligament (5
      patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median,
      31 years).The main clinical manifestations of PNET in the female genital tract
      are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement,
      and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower
      abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before
      the operations and reduced to normal when the diseases were controlled, while the
      levels increased as the tumor was progressive. Results for the most commonly used
      immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin
      in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors.
      Ten patients underwent surgical resection. Nine of them underwent preoperative
      or/and postoperative combination chemotherapy. The follow-up of 10 patients were
      available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom
      experiencing recurrence. CONCLUSIONS: Primitive neuroectodermal tumor is very
      rare and can originate from any part of the female genital tract. The tumors had
      different manifestations but the same pathologic features. CA125 may be an
      important marker for prognosis and follow-up of PNET of the female internal
      genital tract.

PMID- 24463643
TI  - Complications after the treatment of endometrial cancer: a prospective study
      using the French-Italian glossary.
AB  - INTRODUCTION: The evaluation of treatment complications is crucial in modern
      oncology because they heavily influence the every day life of patients. Several
      authors confirmed the reproducibility of the French-Italian glossary to score the
      complications in patients with endometrial cancer after radiotherapy (RT), but
      the treatment of endometrial carcinoma is primarily surgical and chemotherapy is
      often used for high-risk disease. OBJECTIVES: This study aimed to analyze the
      incidence of complications in our patients treated for endometrial cancer and to
      verify whether the glossary is a suitable instrument in the description of
      complications after surgery, RT, and chemotherapy. METHODS: The data of patients
      affected by endometrial cancer treated in the Gynecology and Obstetrics Academic
      Department, Azienda Ospedaliera Mauriziano Umberto I in Turin from 2000 to 2009
      (with surgery alone or integrated treatments) were prospectively collected, and
      complications were described using the glossary. Every patient included in the
      analyses had a minimum of 18 months follow-up. RESULTS: Of the 271 patients, 68
      (25%) experienced at least 1 complication with 87 overall complications. Most of
      the complications were mild (63%) and were found in the urinary (30%) or
      cutaneous systems (30%). Forty-four (50%) complications appeared within 1 year
      after treatment, but 9 (10%) complications appeared after 60 months of follow-up.
      Patients who were submitted to both surgery and RT showed a trend of higher rate
      of at least 1 complication (19/58 [32.7%]) if compared with surgery alone (36/135
      [26.6%]), even if the difference was not statistically significant (P = 0.09).
      The incidence of complications in patients treated or not with lymphadenectomy
      was not statistically different (P = 0.088), whereas patients treated with
      laparotomy had a higher rate of cutaneous complications if compared with the
      laparoscopic approach (P = 0.018). The glossary included all observed
      complications. CONCLUSIONS: One every 4 women treated for endometrial cancer
      develops a complication. Clinicians should check for complications especially
      after integrated treatments maintaining surveillance even in the long term. The
      glossary is a comprehensive instrument to describe the complications of
      endometrial cancer, regardless of the type of treatment delivered.

PMID- 24463644
TI  - High performance few-layer GaS photodetector and its unique photo-response in
      different gas environments.
AB  - Layered GaS nanosheets have been attracting increasing research interests due to
      their highly anisotropic structural, electrical, optical, and mechanical
      properties, which are useful for many applications. However, single-layer or few
      layer GaS-based photodetectors have been rarely reported. Here a few-layer GaS
      two-terminal photodetector with a fast and stable response has been fabricated.
      It shows different photo-responses in various gas environments. A higher photo
      response (64.43 A W(-1)) and external quantum efficiency (EQE) (12,621%) is
      obtained in ammonia (NH3) than in air or oxygen (O2). A theoretical investigation
      shows that the charge transfer between the adsorbed gas molecules and the
      photodetector leads to the different photo-responses.

PMID- 24463645
TI  - Synthesis, structure-activity relationship of iodinated-4-aryloxymethyl-coumarins
      as potential anti-cancer and anti-mycobacterial agents.
AB  - A series of new iodinated-4-aryloxymethylcoumarins 6, 8 and 10 have been obtained
      from the reaction of various 4-bromomethylcoumarins 4 with 2-iodophenol 5, 3
      iodophenol 7 and 4-iodophenol 9 respectively. All the title compounds were
      screened for anticancer activity against two cancer cell lines (MDA-MB human
      adenocarcinoma mammary gland and A-549 human lung carcinoma) and two
      mycobacterial strains (Mycobacterium tuberculosis H37 RV and Mycobacterium
      phlei). The SAR results indicate that nine compounds are potent, among these 10h
      and 10i having chlorine are most effective. This is the first report assigning in
      vitro anti-mycobacterial, anticancer and structure-activity relationship for this
      new class of iodinated-4-aryloxymethyl-coumarins.

PMID- 24463646
TI  - [Deep brain stimulation for Parkinson's disease: timing and patient selection].
AB  - Deep brain stimulation (DBS) is an effective and evidence-based treatment option
      for Parkinson's disease. Studies have shown that DBS has good and long-term
      effects on motor function and quality of life for patients in an advanced stage
      of the disease and that it is more effective than medical therapy alone.
      Moreover, a favorable effect of DBS could also be detected at an earlier stage of
      the disease. On the other hand, possible risks and side effects of the procedure
      need to be taken into consideration. These can manifest as procedure-related
      complications, such as bleeding and infections in addition to stimulation
      associated phenomena, such as neuropsychiatric disorders and motor side effects.
      Despite the good effects of DBS important issues still need to be addressed which
      will be discussed in this article considering the results of several new
      randomized and controlled clinical studies. For patients with Parkinson's disease
      with early fluctuations and dyskinesia, DBS has been found to be superior to the
      best pharmaceutical treatment; therefore, DBS can be considered as a treatment
      option in the earlier course of the disease. The diagnostic evaluation and the
      exclusion of contraindications are crucial for patient selection. The choice of
      the target should be based on the individual symptoms in patients although the
      subthalamic nucleus (STN) can be considered the standard target. In every case an
      individual assessment of chances and risks must be conducted and realistic goals
      and reasonable expectations must be defined.

PMID- 24463647
TI  - [Deep brain stimulation for addiction, anorexia and compulsion. Rationale,
      clinical results and ethical implications].
AB  - BACKGROUND: As an established treatment for movement disorders, the application
      of deep brain stimulation (DBS) for psychiatric indications has been investigated
      for almost 15 years. A CE label (also FDA approval) has recently been obtained
      for treatment of refractory obsessive-compulsive disorder (OCD). OBJECTIVES: This
      article aims at illustrating the current state of DBS in the treatment of
      refractory OCD. In addition, initial experimental approaches to investigate the
      potential use of DBS in substance addiction and anorexia nervosa (AN) will also
      be outlined as both disorders share some common features with OCD. MATERIALS AND
      METHODS: The present review is based on a keyword literature search (PubMed)
      while taking into account relevant references and own investigations RESULTS:
      Although the number of clinical trials for treatment of refractory OCD is limited
      and sample sizes are small, there is some evidence for a substantial improvement,
      a so-called full response of OCD symptoms under DBS. However, not all patients
      benefit from the intervention. Regarding substance addiction and AN, data are
      scarce and are only indicative of a potential benefit at most. DISCUSSION:
      Present data regarding the clinical benefits of DBS in OCD are encouraging and
      open up new avenues for the treatment of therapy refractory patients. However,
      several aspects, such as mechanisms of action, predictors and long-term side
      effect profiles, are incomplete or even unknown. In the case of addiction and AN,
      DBS remains purely experimental, at least for the moment. Hence, clinical trials
      should remain the gold standard for all three indications.

PMID- 24463648
TI  - [Technical innovations in deep brain stimulation].
AB  - Although first introduced about 25 years ago deep brain stimulation (DBS)
      technology is still evolving at a high rate and most innovations have been
      developed as a result of pressure from increasing commercial competition.
      Technical innovations from recent years include rechargeable generators and new
      stimulation paradigms. Current and upcoming developments mainly aim at prediction
      of stimulation and unwanted side effects and hence improvement in safety and
      treatment efficacy. Some of the future keynote DBS technologies are summarized in
      this survey. 

PMID- 24463650
TI  - [Rapid detection of a depressive disorder in persons with epilepsy. Validation of
      a German version of the NDDI-E].
AB  - The prevalence of psychiatric disorders in people with epilepsy is high.
      Depression and anxiety disorders are especially frequent. These comorbid
      disorders are, however, easily overlooked. The neurological disorders depression
      inventory for epilepsy (NDDI-E) was developed and validated as a screening
      instrument with six questions. The aim of the present study was to validate a
      German version of the NDDI-E. After translation into German and back translation
      into English, the NDDI-E was presented to 144 patients at the Bethel Epilepsy
      Center. The Beck depression inventory II (BDI-II), the revised symptom check list
      by Derogatis (SCL-90-R) and the state-trait anxiety inventory (STAI) were also
      used. The patients were examined using the mini international neuropsychiatric
      interview plus (MINI Plus). The German version of the NDDI-E proved to be valid,
      internally consistent and easy to use. 

PMID- 24463649
TI  - [Intensive care unit acquired weakness. Pathogenesis, treatment, rehabilitation
      and outcome].
AB  - The diagnosis of intensive care unit acquired weakness (ICUAW) in the setting of
      neurological rehabilitation is steadily increasing. This is due to the fact that
      the intensive care of patients with sepsis or after cardiac or abdominal surgery
      is improving. A longer duration of respiratory weaning and comorbidities
      frequently complicate rehabilitation. Clinically, patients present with a flaccid
      (tetra) paresis and electrophysiological studies have shown axonal damage.
      Besides involvement of peripheral nerves, muscle can also be affected (critical
      illness myopathy) leading to ICUAW with inconstant myopathic damage patterns
      found by electrophysiological testing. Mixed forms can also be found. A specific
      therapy for ICUAW is not available. Early mobilization to be initiated on the
      intensive care unit and commencing neurological rehabilitation improve the
      outcome of ICUAW. This review highlights the current literature regarding the
      etiology and diagnosis of ICUAW. Furthermore, studies about rehabilitation and
      outcome of ICUAW are discussed. 

PMID- 24463651
TI  - Confirming the causal role of advanced glycation end-products in arterial
      stiffening.

PMID- 24463655
TI  - Robotics in benign gynecologic surgery: where should we go?

PMID- 24463656
TI  - Robotics in gynecology: is the glass half empty or half full?

PMID- 24463657
TI  - Robotic compared with laparoscopic sacrocolpopexy: a randomized controlled trial.
AB  - OBJECTIVE: Laparoscopic and robotic sacrocolpopexy are widely used for pelvic
      organ prolapse (POP) treatment. Evidence comparing outcomes and costs is lacking.
      We compared costs and clinically relevant outcomes in women randomized to
      laparoscopic sacrocolpopexy compared with robotic sacrocolpopexy. METHODS:
      Participants with symptomatic stage POP II or greater, including significant
      apical support loss, were randomized to either laparoscopic or robotic
      sacrocolpopexy. We compared surgical costs (including costs for robot, initial
      hospitalization) and rehospitalization within 6 weeks. Secondary outcomes
      included postoperative pain, POP quantification, symptom severity and quality of
      life, and adverse events. RESULTS: We randomized 78 women (mean age 59 years):
      laparoscopic (n=38) and robotic (n=40). The robotic sacrocolpopexy group had
      higher initial hospital costs ($19,616 compared with $11,573, P<.001) and over 6
      weeks, hospital costs remained higher for robotic sacrocolpopexy ($20,898
      compared with $12,170, P<.001). When we excluded costs of robot purchase and
      maintenance, we did not detect a statistical difference in initial day of surgery
      costs of robotic compared with laparoscopic ($12,586 compared with $11,573;
      P=.160) or hospital costs over 6 weeks ($13,867 compared with $12,170; P=.060).
      The robotic group had longer operating room times (202.8 minutes compared with
      178.4 minutes, P=.030) and higher pain scores 1 week after surgery (3.5+/-2.1
      compared with 2.6+/-2.2; P=.044). There were no group differences in symptom
      bother by Pelvic Floor Distress Inventory, POP stage, or rate of adverse events.
      CONCLUSION: Costs of robotic sacrocolpopexy are higher than laparoscopic, whereas
      short-term outcomes and complications are similar. Primary cost differences
      resulted from robot maintenance and purchase costs. CLINICAL TRIAL REGISTRATION:
      Clinicaltrials.gov, www.clinicaltrials.gov, NCT01124916. LEVEL OF EVIDENCE: I.

PMID- 24463658
TI  - Milestones to optimal adoption of robotic technology in gynecology.
AB  - Minimally invasive technology, especially robotics, is gaining widespread
      acceptance and is becoming the standard approach for the treatment of both benign
      and malignant gynecologic conditions in centers across the country. However,
      there are challenges on a systems-based level to the implementation of a robotic
      program. Prominent among the concerns is the length of the learning curve, team
      building, quality of life, and financial and various organizational challenges.
      The purpose of this review article is to address those challenges as milestones
      on the progress to a successful robotics program and explore possible solutions. 

PMID- 24463659
TI  - Association between topiramate and zonisamide use during pregnancy and low birth
      weight.
AB  - OBJECTIVE: To assess the possible effects of topiramate and zonisamide use during
      pregnancy on fetal growth. METHODS: The study population was the singleton
      liveborns born to women who enrolled in the North American Antiepileptic Drug
      Pregnancy Registry between 1997 and 2012. Data were collected through telephone
      interviews at enrollment, 7 months of gestation, and postpartum. The prevalence
      of small for gestational age at birth among neonates exposed to topiramate and to
      zonisamide when either was used as monotherapy during pregnancy was compared with
      that among neonates exposed to lamotrigine monotherapy, a weight-neutral therapy,
      and the most common antiepileptic drug in the Registry. Relative risks (RRs) and
      95% confidence intervals (CIs) were estimated with multivariable log-binomial
      regression to control for potential confounders. RESULTS: Data were available for
      347 topiramate, 98 zonisamide, and 1,581 lamotrigine-exposed neonates. The mean
      gestational length was 39 weeks for all comparison groups. Prenatal exposure to
      topiramate or zonisamide was associated with a mean lower birth weight of 221 and
      202 g, respectively, and a mean lesser neonatal length of 1 cm as compared with
      lamotrigine exposure (p<.01). The prevalence of small for gestational age was
      6.8% for lamotrigine, 17.9% for topiramate (RR 2.4, 95% CI 1.8-3.3) and 12.2% for
      zonisamide (RR 1.6, 0.9-2.8). Similar results were found when a group of 457
      unexposed neonates was used as the reference. CONCLUSIONS: Topiramate and
      zonisamide have been shown to reduce weight in adults. Our finding of a decrease
      in mean birth weight and length among neonates exposed in utero raises concern.
      LEVEL OF EVIDENCE: II.

PMID- 24463660
TI  - Validation of the joint commission exclusion criteria for elective early-term
      delivery.
AB  - OBJECTIVE: To evaluate whether current Joint Commission (JC) exclusion criteria
      for measure PC-01, "Elective Delivery" before 39 weeks of gestation, accurately
      identify valid, codeable indications for planned early-term delivery. METHODS: We
      performed a review and critical analysis of all cases recorded as noncompliant
      for the measure in a large health care system during the second half of 2012.
      RESULTS: During the study period, of 107,145 total deliveries, 205 cases were
      reported as noncompliant with PC-01. Ten percent of compliance fallouts (ie,
      cases coded as noncompliant) resulted from valid indications for delivery
      identifiable by International Classification of Diseases, 9th Revision, Clinical
      Modification (ICD-9-CM) coding not included on the JC exclusion list; these were
      primarily unusual or extreme variations of these conditions. Twenty-five percent
      of fallouts represented valid indications not represented by an ICD-9-CM code.
      Eight percent of cases were reported as fallouts as a result of imprecise
      physician charting; only 2% represented chart abstraction errors. Fifty-five
      percent of cases involved stated indications for early-term delivery not
      generally recognized as such by the medical community. Compliance rates of 98%
      are achievable across a large population using the current ICD-9-CM-based metric
      for compliance assessment used by the JC (PC-01). The current exclusion list does
      not appear to be amenable to further improvement by inclusion of more or
      different ICD-9-CM codes. However, given the low volumes generated using the
      current PC-01 denominator definition, approximately 60% of facilities would have
      compliance rates below a 95% benchmark with even a single justified outlier if
      analyzed on a quarterly basis. CONCLUSION: Our data validate the current JC
      exclusion criteria for this measure, which identify the vast majority of valid
      indications for early-term delivery used by obstetrician-gynecologists and
      identifiable with ICD-9-CM codes. LEVEL OF EVIDENCE: III.

PMID- 24463661
TI  - Preterm birth rates in a prematurity prevention clinic after adoption of
      progestin prophylaxis.
AB  - OBJECTIVE: To evaluate whether progestin prophylaxis influenced the odds of
      recurrent spontaneous preterm birth among pregnant women with a previous preterm
      birth. METHODS: A retrospective cohort study was performed evaluating outcomes of
      pregnant women with one or more previous preterm births who received prenatal
      care in a single academic prematurity clinic. Care algorithms were determined and
      revised by a single supervising physician. Progestin prophylaxis was adopted in
      2004 with accelerated access to the first clinic visit adopted in 2008. Rates of
      preterm birth before 37, 35, and 32 weeks of gestation were compared over time.
      RESULTS: One thousand sixty-six women with a history of one or more spontaneous
      preterm births received care in the prematurity clinic and were delivered between
      January 1, 1998, and June 30, 2012. The gestational age at initiation of prenatal
      care declined significantly after adoption of an accelerated appointment process
      (median of 19.1 weeks before 2003, 16.2 weeks from 2004 to 2007, and 15.2 weeks
      from 2008 to 2012, P<.01), and progestin use increased from 50.8% in 2004-2007 to
      80.3% after 2008 (P<.01). After adjustment for race, smoking, cerclage, and
      number of prior preterm deliveries, we noted a statistically significant
      decreased odds of spontaneous preterm birth in years 2008-2012 compared with 1998
      2007 before 37 (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.58
      0.97) and 35 (adjusted OR 0.70, 95% CI (.52-0.94) weeks of gestation. CONCLUSION:
      Adoption of prophylactic progestin treatment was associated with a decreased odds
      of recurrent preterm birth before 37 or 35 weeks of gestation after adoption of
      an aggressive program to facilitate early initiation of progestin treatment.
      LEVEL OF EVIDENCE: II.

PMID- 24463662
TI  - Maternal vitamin D status and small-for-gestational-age offspring in women at
      high risk for preeclampsia.
AB  - OBJECTIVE: To examine the association between second-trimester maternal serum 25
      hydroxyvitamin D concentrations and risk of small for gestational age (SGA) in
      singleton live births. METHODS: We assayed serum samples at 12-26 weeks of
      gestation for 25-hydroxyvitamin D in a sample of participants in a multicenter
      clinical trial of low-dose aspirin for the prevention of preeclampsia in high
      risk women (n=792). Multivariable log-binomial regression models were used to
      assess the association between 25-hydroxyvitamin D and risk of SGA (birth weight
      less than the 10 percentile for gestational age) after adjustment for confounders
      including maternal prepregnancy obesity, race, treatment allocation, and risk
      group. RESULTS: Thirteen percent of neonates were SGA at birth. Mean (standard
      deviation) 25-hydroxyvitamin D concentrations were lower in women who delivered
      SGA (57.9 [29.9] nmol/L) compared with non-SGA neonates (64.8 [29.3] nmol/L,
      P=.028). In adjusted models, 25-hydroxyvitamin D concentrations of 50-74 nmol/L
      and 75 nmol/L or greater compared with less than 30 nmol/L were associated with
      43% (95% confidence interval [CI] 0.33-0.99) and 54% (95% CI 0.24-0.87)
      reductions in risk of SGA, respectively. Race and maternal obesity each modified
      this association. White women with 25-hydroxyvitamin D 50 nmol/L or greater
      compared with less than 50 nmol/L had a 68% reduction in SGA risk (adjusted risk
      ratio 0.32, 95% CI 0.17-0.63) and nonobese women with 25-hydroxyvitamin D 50
      nmol/L or greater compared with less than 50 nmol/L had a 50% reduction in SGA
      risk (adjusted risk ratio 0.50, 95% CI 0.31-0.82). There was no association
      between 25-hydroxyvitamin D and risk of SGA in black or obese mothers.
      CONCLUSION: Maternal vitamin D status in the second trimester is associated with
      risk of SGA among all women and in the subgroups of white and nonobese women.
      LEVEL OF EVIDENCE: II.

PMID- 24463664
TI  - High-risk and low-risk human papillomavirus and the absolute risk of cervical
      intraepithelial neoplasia or cancer.
AB  - OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia
      (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk
      human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In
      this prospective cohort study, consecutive liquid-based cervical cytology samples
      were collected from women screened for cervical cancer in Copenhagen, Denmark,
      during 2002-2005. Samples were tested with a clinical test for 13 high-risk and
      five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in
      a nationwide pathology register for up to 10.5 years for development of CIN 3 or
      worse. RESULTS: The 8-year absolute risk of CIN 3 or worse was 1.1% (95%
      confidence interval [CI] 1.0-1.3%) for HPV-negative women; 1.7% (0.8-2.6%) for
      low-risk HPV-positive women without concurrent high-risk HPV; 17.4% (16.4-18.5%)
      for high-risk HPV-positive women without concurrent low-risk HPV; and 15.9% (13.5
      18.3%) for women with concurrent high-risk and low-risk HPV. The 8-year absolute
      risk of CIN 3 or worse after a negative high-risk HPV test (irrespective of low
      risk HPV status) was lower than after a normal cytology result among women aged
      younger than 30 years (3.5% [95% CI, 2.9-4.0%] compared with 6.9% [6.2-7.5%],
      P<.001) and women aged 30 years or older (0.7% [95% CI, 0.6-0.9%] compared with
      1.8% [95% CI, 1.6-2.0%], P<.001). CONCLUSION: A negative high-risk HPV test
      provides greater long-term reassurance against CIN 3 or worse than normal
      cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical
      cancer screening should not include testing for low-risk HPV types. LEVEL OF
      EVIDENCE: II.

PMID- 24463663
TI  - Three-year risk of cervical precancer and cancer after the detection of low-risk
      human papillomavirus genotypes targeted by a commercial test.
AB  - OBJECTIVE: To investigate the risk of cervical precancer and cancer associated
      with detection of human papillomavirus (HPV) 6, 11, and 42. METHODS: We used data
      from the New Mexico Human Papillomavirus Pap Registry. A stratified sample of
      59,644 residual cervical cytology specimens from a population of 379,000
      underwent HPV genotyping. We measured the 3-year cumulative incidence of cervical
      intraepithelial neoplasia grade 2 or more severe (CIN 2+) and grade 3 or more
      severe (CIN 3+) after detection of single HPV 6, 11, or 42 infections or single
      or multiple infections of HPV 6, 11, or 42 ("HPV 6, 11, 42, or combinations";
      n=581). RESULTS: The overall prevalence of a single infection of HPV 6, 11, or 42
      was 0.8% (95% confidence interval [CI] 0.7-0.9%). The 3-year risks of CIN 2+ and
      CIN 3+ after HPV 6, 11, 42, or combinations infections (n=581) were 0.4% (CI 0.1
      0.7%) for CIN 2+ and 0.0% for CIN 3+ (nota bene, no CI was calculable because no
      events occurred), respectively. By comparison, the 3-year risks of CIN 2+ and CIN
      3+ after a negative HPV result (n=27,522) were 0.2% (95% CI 0.1-0.2%) and 0.1%
      (95% CI 0.0-0.1%), respectively. CONCLUSION: Detection of HPV 6, 11, 42, or
      combinations in the absence of high-risk HPV types does not identify women at
      increased 3-year risk for cervical precancer. Testing for HPV 6, 11, 42, or
      combinations of those types should be discontinued because it has no proven
      benefit to patients. LEVEL OF EVIDENCE: II.

PMID- 24463665
TI  - Ovarian cancer rates after hysterectomy with and without salpingo-oophorectomy.
AB  - OBJECTIVE: To estimate ovarian and peritoneal cancer rates after hysterectomy
      with and without salpingo-oophorectomy for benign conditions. METHODS: All
      patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser
      Permanente Northern California, an integrated health organization. Incidence
      rates per 100,000 person-years were calculated. RESULTS: Of 56,692 patients, the
      majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7%
      had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy
      alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow
      up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years,
      respectively. Age-standardized rates (per 100,000 person-years) of ovarian or
      peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with
      hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral
      salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral
      salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for
      those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and
      unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with
      hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing
      hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a
      hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those
      undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28).
      CONCLUSIONS: The removal of both ovaries decreases the incidence of ovarian and
      peritoneal cancers. Removal of one ovary might also decrease the incidence of
      ovarian cancer but warrants further investigation. LEVEL OF EVIDENCE: II.

PMID- 24463666
TI  - Value of symptom-triggered diagnostic evaluation for ovarian cancer.
AB  - OBJECTIVE: To evaluate the potential harms and ovarian cancer outcomes associated
      with symptom-triggered diagnostic evaluation of all women with symptoms of
      ovarian cancer. METHODS: Five thousand twelve women older than age 40 years were
      prospectively enrolled in a cohort study of proactive symptom-triggered
      diagnostic evaluation. Women who tested positive on a symptom index were offered
      testing with CA 125 and transvaginal ultrasonography. Results of these tests and
      any subsequent procedures were recorded. Assessment of ovarian cancer outcomes
      for all participants through Surveillance, Epidemiology, and End Results was
      performed 1 year after enrollment was complete. RESULTS: A positive symptom index
      was found in 241 (4.8%) participating patients, and 211 (88%) underwent CA 125
      testing, transvaginal ultrasound screening, or both. Twenty surgical procedures
      (laparoscopy, laparotomy, vaginal) were performed in the study population (0.4%
      of participating women). However, only six (0.12%) were performed for a
      suspicious ovarian mass and only four (0.08%) were performed solely as a result
      of study participation. A total of eight ovarian cancers were diagnosed, 31-843
      days after symptom assessment (50% distant, 50% local or regional). Of the two
      cancers diagnosed within 6 months, one was symptom index-positive. CONCLUSIONS:
      Proactive symptom-triggered diagnostic evaluation for ovarian cancer results in
      minimal unindicated surgery. A small number of ovarian cancers was identified
      solely on the basis of symptom-triggered diagnostic testing. LEVEL OF EVIDENCE:
      II.

PMID- 24463667
TI  - Relationship between ultrasound viewing and proceeding to abortion.
AB  - OBJECTIVE: Ultrasound scanning is a routine part of preprocedure abortion care,
      and many health care providers offer patients the opportunity to view their
      ultrasound images. It has been speculated that ultrasound viewing will dissuade
      women from having an abortion. We examine whether viewing the image is associated
      with choosing to continue the pregnancy. METHODS: Data from medical records for
      15,575 visits by women seeking abortion care at a large, urban abortion provider
      in 2011 were analyzed for factors associated with choosing to continue the
      pregnancy. All patients received a preprocedure ultrasound scan and were offered
      the opportunity to view the image. RESULTS: Patients opted to view the ultrasound
      image 42.5% of the time. Nearly all pregnancies (98.8%) were terminated: 98.4% of
      pregnancies among women who viewed their ultrasound images and 99.0% of
      pregnancies among the patients who did not. Among women with high decision
      certainty, viewing was not associated with deciding to continue the pregnancy.
      Viewing was significantly associated with deciding to continue the pregnancy only
      among the 7.4% of women who reported medium or low decision certainty about
      having an abortion (adjusted odds ratio 3.21, 95% confidence interval 1.18-8.73).
      CONCLUSION: Voluntarily viewing the ultrasound image may contribute to a small
      proportion of women with medium or low decision certainty deciding to continue
      the pregnancy; such viewing does not alter decisions of the large majority of
      women who are certain that abortion is the right decision. LEVEL OF EVIDENCE: II.

PMID- 24463668
TI  - Acceptability and feasibility of phone follow-up after early medical abortion in
      Vietnam: a randomized controlled trial.
AB  - OBJECTIVE: To investigate phone follow-up with a semiquantitative urine pregnancy
      test and symptom checklist as a replacement for universal clinic follow-up after
      medical abortion. METHODS: One thousand four hundred thirty-three women seeking
      early medical abortion at four hospitals in Vietnam were randomized to clinic or
      phone follow-up. Women allocated to clinic follow-up returned to the hospital for
      confirmation of abortion outcome 2 weeks after mifepristone administration. Women
      assigned to phone follow-up completed a semiquantitative pregnancy test at
      initial visit to determine baseline human chorionic gonadotropin range and again
      at home 2 weeks later. Clinic staff called women to review the pregnancy test
      results and symptom checklist. Women who screened positive were referred to the
      clinic. Effectiveness, feasibility, and acceptability of the follow-up methods
      were assessed. RESULTS: The rate of ongoing pregnancy was not significantly
      different between the two groups (clinic: 2.7% phone, 2.5%, relative risk 0.9,
      95% confidence interval 0.99-1.02). Eighty-five percent of women in the phone
      group did not need an additional clinic visit. Phone follow-up was highly
      effective in screening for ongoing pregnancy with a sensitivity and specificity
      of 92.8% and 90.6%, respectively. Specificity of the pregnancy test alone (eg,
      without the symptom checklist) was higher (95.7%). CONCLUSION: Phone follow-up
      offers a feasible and effective approach to identify women with ongoing pregnancy
      after early medical abortion. When used with the semiquantitative pregnancy test,
      the symptom checklist offered no additional benefit and decreased the specificity
      of the screening. Given its effectiveness and ease of use, the semiquantitative
      pregnancy test alone could replace routine clinic follow-up after early medical
      abortion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT01150422. LEVEL OF EVIDENCE: I.

PMID- 24463669
TI  - Oral antibiotics to prevent postoperative urinary tract infection: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate whether nitrofurantoin prophylaxis prevents postoperative
      urinary tract infection (UTI) in patients receiving transurethral catheterization
      after pelvic reconstructive surgery. METHODS: In a randomized, double-blind,
      placebo-controlled trial, participants undergoing pelvic reconstructive surgery
      were randomized to 100 mg nitrofurantoin or placebo once daily during
      catheterization if they were: 1) discharged with a transurethral Foley or
      performing intermittent self-catheterization; or 2) hospitalized overnight with a
      transurethral Foley. Our primary outcome was treatment for clinically suspected
      or culture-proven UTI within 3 weeks of surgery. Statistical analysis was
      performed by chi2 and logistic regression. Assuming 80% power at a P value of
      .05, 156 participants were needed to demonstrate a two-thirds reduction in UTI.
      RESULTS: Of 159 participants, 81 (51%) received nitrofurantoin and 78 (49%)
      received placebo. There were no significant differences in baseline demographics,
      intraoperative characteristics, duration and type of catheterization, or
      postoperative hospitalization, except a lower rate of hysterectomy in the
      nitrofurantoin group. Nitrofurantoin prophylaxis did not reduce the risk of UTI
      treatment within 3 weeks of surgery (22% UTI with nitrofurantoin compared with
      13% UTI with placebo, relative risk 1.73, 95% confidence interval 0.85-3.52,
      P=.12). Urinary tract infection treatment was higher in premenopausal women,
      lower in diabetics, and increased with longer duration of catheterization. In
      logistic regression adjusting for menopause, diabetes, preoperative postvoid
      residual volume, creatinine clearance, hysterectomy, and duration of
      catheterization, there was still no difference in UTI with nitrofurantoin as
      compared with placebo. CONCLUSION: Prophylaxis with daily nitrofurantoin during
      catheterization does not reduce the risk of postoperative UTI in patients
      receiving short-term transurethral catheterization after pelvic reconstructive
      surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov,
      NCT01450800. LEVEL OF EVIDENCE: I.

PMID- 24463670
TI  - Adverse pregnancy outcomes related to advanced maternal age compared with smoking
      and being overweight.
AB  - OBJECTIVE: To investigate the association between advanced maternal age and
      adverse pregnancy outcomes and to compare the risks related to advanced maternal
      age with those related to smoking and being overweight or obese. METHODS: A
      population-based register study including all nulliparous women aged 25 years and
      older with singleton pregnancies at 22 weeks of gestation or greater who gave
      birth in Sweden and Norway from 1990 to 2010; 955,804 women were analyzed. In
      each national sample, adjusted odds ratios (ORs) of very preterm birth,
      moderately preterm birth, small for gestational age, low Apgar score, fetal
      death, and neonatal death in women aged 30-34 years (n=319,057), 35-39 years
      (n=94,789), and 40 years or older (n=15,413) were compared with those of women
      aged 25-29 years (n=526,545). In the Swedish sample, the number of additional
      cases of each outcome associated with maternal age 30 years or older, smoking,
      and overweight or obesity, respectively, was estimated in relation to a low-risk
      group of nonsmokers of normal weight and aged 25-29 years. RESULTS: The adjusted
      OR of all outcomes increased by maternal age in a similar way in Sweden and
      Norway; and the risk of fetal death was increased even in the 30- to 34-year-old
      age group (Sweden n=826, adjusted OR 1.24, 95% confidence interval [CI] 1.13
      1.37; Norway n=472, adjusted OR 1.26, 95% CI 1.12-1.41). Maternal age 30 years or
      older was associated with the same number of additional cases of fetal deaths
      (n=251) as overweight or obesity (n=251). CONCLUSION: For the individual woman,
      the absolute risk for each of the outcomes was small, but for society, it may be
      significant as a result of the large number of women who give birth after the age
      of 30 years. LEVEL OF EVIDENCE: II.

PMID- 24463672
TI  - Blood transfusion during pregnancy, birth, and the postnatal period.
AB  - OBJECTIVES: To identify risk factors for transfusion and trends in transfusion
      rates across pregnancy and the postnatal period. METHODS: Linked hospital and
      birth data on all births in hospitals in New South Wales, Australia, between 2001
      and 2010 were used to identify blood transfusions for women during pregnancy, at
      birth, and in the 6 weeks postpartum. Poisson regression was used to identify
      risk factors for red cell transfusion in the birth admission. Separate models
      were fitted for cesarean and vaginal births. RESULTS: Between 2001 and 2010,
      there were 12,147 transfusions across 891,914 pregnancies, with a transfusion
      rate of 1.4%. The transfusion rate increased steadily from 1.2% in 2001 to 1.6%
      in 2010. The majority of transfusions (91%) occurred during the birth admission,
      and 81% of these transfusions were associated with a diagnosis of hemorrhage.
      Women with bleeding or platelet disorders (vaginal: number transfused 529,
      relative risk [RR] 7.8, 99% confidence interval [CI] 6.9-8.7, cesarean: n=592, RR
      8.7, CI 7.7-9.7) and placenta previa: (vaginal n=73, RR 4.6, CI 3.4-6.3,
      cesarean: n=875, RR 5.7, CI 5.1-6.4) were at highest risk of transfusion. Among
      vaginal births, increased risk was evident for forceps (n=1,036, RR 2.8, CI 2.5
      3.0) or vacuum births (n=1,073, RR 1.9, CI 1.7-2.0) compared with nonoperative
      births. CONCLUSIONS: Rates of obstetric blood product transfusion have increased
      by 33% since 2001, with the majority of this associated with hemorrhage. Women
      with bleeding or platelet disorders and placenta previa are at increased risk of
      transfusion and should be treated accordingly. LEVEL OF EVIDENCE: II.

PMID- 24463671
TI  - Association between stillbirth and illicit drug use and smoking during pregnancy.
AB  - OBJECTIVE: To compare illicit drug and smoking use in pregnancies with and
      without stillbirth. METHODS: The Stillbirth Collaborative Research Network
      conducted a case-control study from March 2006 to September 2008, covering more
      than 90% of deliveries to residents of five a priori-defined geographically
      diverse regions. The study attempted to include all stillbirths and
      representative liveborn controls. Umbilical cord samples from cases and controls
      were collected and frozen for subsequent batch analysis. Maternal serum was
      collected at delivery and batch analyzed for cotinine. RESULTS: For 663
      stillbirth deliveries, 418 (63%) had cord homogenate and 579 (87%) had maternal
      cotinine assays performed. For 1,932 live birth deliveries, 1,050 (54%) had cord
      homogenate toxicology and 1,545 (80%) had maternal cotinine assays performed. A
      positive cord homogenate test for any illicit drug was associated with stillbirth
      (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.16-3.27). The most common
      individual drug was cannabis (OR 2.34 95% CI 1.13-4.81), although the effect was
      partially confounded by smoking. Both maternal self-reported smoking history and
      maternal serum cotinine levels were associated in a dose-response relationship
      with stillbirth. Positive serum cotinine less than 3 ng/mL and no reported
      history of smoking (proxy for passive smoke exposure) also were associated with
      stillbirth (OR 2.06, 95% CI 1.24-3.41). CONCLUSION: Cannabis use, smoking,
      illicit drug use, and apparent exposure to second-hand smoke, separately or in
      combination, during pregnancy were associated with an increased risk of
      stillbirth. Because cannabis use may be increasing with increased legalization,
      the relevance of these findings may increase as well. LEVEL OF EVIDENCE: II.

PMID- 24463673
TI  - Symptom resolution after operative management of complications from transvaginal
      mesh.
AB  - OBJECTIVE: Complications from transvaginal mesh placed for prolapse often require
      operative management. The aim of this study is to describe the outcomes of
      vaginal mesh removal. METHODS: A retrospective review of all patients having
      surgery by the urogynecology group in the department of obstetrics and gynecology
      at our institution for a complication of transvaginal mesh placed for prolapse
      was performed. Demographics, presenting symptoms, surgical procedures, and
      postoperative symptoms were abstracted. Comparative statistics were performed
      using the chi or Fisher's exact test with significance at P<.05. RESULTS: Between
      January 2008 and April 2012, 90 patients had surgery for complications related to
      vaginal mesh and 84 had follow-up data. The most common presenting signs and
      symptoms were: mesh exposure, 62% (n=56); pain, 64% (n=58); and dyspareunia, 48%
      (n=43). During operative management, mesh erosion was encountered unexpectedly in
      a second area of the vagina in 5% (n=4), in the bladder in 1% (n=1), and in the
      bowel in 2% (n=2). After vaginal mesh removal, 51% (n=43) had resolution of all
      presenting symptoms. Mesh exposure was treated successfully in 95% of patients,
      whereas pain was only successfully treated in 51% of patients. CONCLUSION:
      Removal of vaginal mesh is helpful in relieving symptoms of presentation.
      Patients can be reassured that exposed mesh can almost always be successfully
      managed surgically, but pain and dyspareunia are only resolved completely in half
      of patients. LEVEL OF EVIDENCE: III.

PMID- 24463674
TI  - Prevalence and trends of symptomatic pelvic floor disorders in U.S. women.
AB  - OBJECTIVE: To estimate the prevalence and trends of these pelvic floor disorders
      in U.S. women from 2005 to 2010. METHODS: We used the National Health and
      Nutritional Examination Survey from 2005-2006, 2007-2008, and 2009-2010. A total
      of 7,924 nonpregnant women (aged 20 years or older) were categorized as having:
      urinary incontinence (UI)-moderate to severe (3 or higher on a validated UI
      severity index, range 0-12); fecal incontinence-at least monthly (solid, liquid,
      or mucus stool); and pelvic organ prolapse-seeing or feeling a bulge. Potential
      risk factors included age, race and ethnicity, parity, education, poverty income
      ratio, body mass index ([BMI] less than 25, 25-29, 30 or greater), comorbidity
      count, and reproductive factors. Using appropriate sampling weights, weighted chi
      analysis and multivariable logistic regression models with odds ratios and 95%
      confidence intervals (95% CIs) were reported. RESULTS: The weighted prevalence
      rate of one or more pelvic floor disorders was 25.0% (95% CI 23.6-26.3),
      including 17.1% (95% CI 15.8-18.4) of women with moderate-to-severe UI, 9.4% (95%
      CI 8.6-10.2) with fecal incontinence, and 2.9% (95% CI 2.5-3.4) with prolapse.
      From 2005 to 2010, no significant differences were found in the prevalence rates
      of any individual disorder or for all disorders combined (P>.05). After adjusting
      for potential confounders, higher BMI, greater parity, and hysterectomy were
      associated with higher odds of one or more pelvic floor disorders. CONCLUSION:
      Although rates of pelvic floor disorders did not change from 2005 to 2010, these
      conditions remain common, with one fourth of adult U.S. women reporting at least
      one disorder. LEVEL OF EVIDENCE: III.

PMID- 24463675
TI  - Implementation of a national nuchal translucency education and quality monitoring
      program.
AB  - In 2004, leaders in first-trimester aneuploidy screening and a multidisciplinary
      group of experts established the Nuchal Translucency Quality Review Program, a
      national program to standardize education, credentialing, and quality monitoring
      of nuchal translucency. Since its inception, the program has credentialed more
      than 6,600 physician and ultrasonographer participants and collected more than
      2.4 million nuchal translucency measurements. Ongoing quality monitoring is
      conducted through statistical analysis comparing the distribution and standard
      deviation of participants' nuchal translucency measurements against those
      obtained from a standard referent curve. Results of these analyses are
      distributed to participants quarterly and are used to track each participant's
      performance and to trigger performance improvement activities or mandatory
      remediation. This program could serve as a template for future education and
      credentialing programs that include partnerships with academic leaders, national
      professional organizations, and industry. 

PMID- 24463676
TI  - Helminth infections: a new global women's health agenda.
AB  - Emerging evidence over the past decade has implicated helminth infections as
      important yet stealth causes of adverse pregnancy outcomes and impaired women's
      reproductive health. The two most important helminth infections affecting women
      living in poverty in Africa and elsewhere in the developing world are hookworm
      infection and schistosomiasis. In Africa alone, almost 40 million women of
      childbearing age are infected with hookworms, including almost 7 million pregnant
      women who are at greater risk of severe anemia, higher mortality, and
      experiencing poor neonatal outcome (reduced birth weight and increased infant
      mortality). Possibly, tens of millions of women in Africa also suffer from female
      genital schistosomiasis associated with genital itching and pain, stress
      incontinence, dyspareunia, and infertility and experience social stigma and
      depression. Female genital schistosomiasis also is linked to horizontal
      transmission of human immunodeficiency virus (HIV) and acquired immunodeficiency
      syndrome (AIDS) and it may represent one of Africa's major cofactors in its AIDS
      epidemic. There is urgency to expand mass drug administration efforts for
      hookworm and schistosomiasis to include women of reproductive age and to shape
      new policies and advocacy initiatives for women's global health to include
      helminth control. In parallel is a requirement to better link global health
      programs for HIV and AIDS and malaria with helminth control and to simultaneously
      launch initiatives for research and development. 

PMID- 24463677
TI  - Women's health, pregnancy, and the U.S. Food and Drug Administration.

PMID- 24463678
TI  - Diabetic ketoacidosis in pregnancy.
AB  - Pregnancies complicated by diabetic ketoacidosis are associated with increased
      rates of perinatal morbidity and mortality. A high index of suspicion is
      required, because diabetic ketoacidosis onset in pregnancy can be insidious,
      usually at lower glucose levels, and often progresses more rapidly as compared
      with nonpregnancy. Morbidity and mortality can be reduced with early detection of
      precipitating factors (ie, infection, intractable vomiting, inadequate insulin
      management or inappropriate insulin cessation, beta-sympathomimetic use, steroid
      administration for fetal lung maturation), prompt hospitalization, and targeted
      therapy with intensive monitoring. A multidisciplinary approach including a
      maternal-fetal medicine physician, medical endocrinology specialists familiar
      with the physiologic changes in pregnancy, an obstetric anesthesiologist, and
      skilled nursing is paramount. Management principles include aggressive volume
      replacement, initiation of intravenous insulin therapy, correction of acidosis,
      correction of electrolyte abnormalities and management of precipitating factors,
      as well as monitoring of maternal-fetal response to treatment. When diabetic
      ketoacidosis occurs after 24 weeks of gestation, fetal status should be
      continuously monitored given associated fetal hypoxemia and acidosis. The
      decision for delivery can be challenging and must be based on gestational age as
      well as maternal-fetal responses to therapy. The natural inclination is to
      proceed with emergent delivery for nonreassuring fetal status that is frequently
      present during the acute episode, but it is imperative to correct the maternal
      metabolic abnormalities first, because both maternal and fetal conditions will
      likewise improve. Prevention strategies should include education of diabetic
      pregnant women about the risks of diabetic ketoacidosis, precipitating factors,
      and the importance of reporting signs and symptoms in a timely fashion. 

PMID- 24463679
TI  - What is new in the evaluation and treatment of urinary incontinence? Best
      articles from the past year.
AB  - This month, we focus on current research in urinary incontinence. Dr. Kenton
      discusses four recent publications, and each is concluded with a "bottom line"
      that is the take-home message. The complete reference for each can be found in on
      this page, along with direct links to the abstracts. 

PMID- 24463680
TI  - Uterine massage to reduce blood loss after vaginal delivery: a randomized
      controlled trial.

PMID- 24463681
TI  - In reply.

PMID- 24463682
TI  - Risk factors for anal intraepithelial neoplasia in women with genital dysplasia.

PMID- 24463683
TI  - In reply.

PMID- 24463684
TI  - Antiphospholipid antibodies in stillbirth.

PMID- 24463685
TI  - In reply.

PMID- 24463691
TI  - ACOG Practice Bulletin No. 141: management of menopausal symptoms.
AB  - Vasomotor and vaginal symptoms are cardinal symptoms of menopause. Vasomotor
      symptoms can be particularly troubling to women and are the most commonly
      reported menopausal symptoms, with a reported prevalence of 50-82% among U.S.
      women who experience natural menopause (1, 2). The occurrence of vasomotor
      symptoms increases during the transition to menopause and peaks approximately 1
      year after the final menstrual period (3-5). The purpose of this document is to
      provide evidence-based guidelines for the treatment of vasomotor and vaginal
      symptoms related to natural and surgical menopause. (Treatment of menopausal
      symptoms in cancer survivors is discussed in the American College of
      Obstetricians and Gynecologists' Practice Bulletin Number 126, Management of
      Gynecologic Issues in Women With Breast Cancer.). 

PMID- 24463692
TI  - ACOG Committee Opinion No. 583: predispute, voluntary, binding arbitration.
AB  - : Arbitration is a form of dispute resolution that is an alternative to 'taking a
      case to court.' Weighing the potential advantages and disadvantages, predispute
      arbitration may represent a valid alternative dispute resolution strategy for
      physicians and patients. When correctly prepared, contractual agreements between
      patients and physicians for predispute, voluntary, binding arbitration can
      satisfy both individual and societal needs and, at the same time, meet relevant
      ethical principles. 

PMID- 24463693
TI  - ACOG: Committee Opinion No. 584: oocyte cryopreservation.
AB  - : In 2013, the American Society for Reproductive Medicine and the Society for
      Assisted Reproductive Technology published a joint document, Mature Oocyte
      Cryopreservation: A Guideline, which addresses advances in techniques to freeze
      human eggs that have resulted in significant recent improvements in pregnancy
      success. Based on the current state of evidence, modern procedures to
      cryopreserve oocytes should no longer be considered experimental. The American
      College of Obstetricians and Gynecologists' Committee on Gynecologic Practice
      endorses the joint document and encourages its use by Fellows. There are not yet
      sufficient data to recommend oocyte cryopreservation for the sole purpose of
      circumventing reproductive aging in healthy women. 

PMID- 24463694
TI  - Outcome in excised thymomas: role of prognostic factors and impact of additional
      malignancies on survival.
AB  - BACKGROUND AND AIMS: Although the management of thymomas has been extensively
      evaluated, the value of prognostic factors in the outcome of these patients
      remains unclear. METHODS AND RESULTS: The medical records of all patients who
      underwent resection of thymoma between January 1985 and September 2010 at a
      single thoracic unit were reviewed. Patients were followed up with reference to
      disease recurrence and development of additional malignancies (AM). Total
      thymectomy was performed in all 68 cases. Mean follow-up time was four years.
      Mean survival was 63.9 months. Mean disease-free interval was 13 months. Factors
      affecting prognosis were Masaoka staging and WHO histological sub-type. Patients
      with thymomas had a higher risk of developing AM when compared with a control
      population of individuals with other tumours (p = 0.0002). Among thymomas, the
      cortical subtype was associated with a higher risk of AM (p = 0.047) and
      mortality (p = 0.001). CONCLUSIONS: This data confirms that Masaoka staging and
      WHO histologic sub-type are the most important prognostic factors in patients
      with thymoma. Moreover, thymomas predominantly arising from the thymic cortex are
      associated with a higher risk of developing other malignancies and with poorer
      survival. The cortical origin of thymoma could therefore be considered as a
      significant prognostic factor.

PMID- 24463695
TI  - The symmetry detection mechanisms are color selective.
AB  - We investigated the role of color in the feature integration process for global
      form perception. For this, we used a 2AFC noise masking paradigm to measure the
      color selectivity of the symmetry detection mechanism. In each trial, a vertical
      symmetric target was randomly presented in one of the two intervals while a
      random dot control, in the other. The observers' task was to determine which
      interval contained the symmetric target. The image elements varied in
      chromaticity. The target density threshold was measured at various combinations
      of target and mask chromaticity. A noise mask with the same chromaticity as the
      target always produced the largest masking effect (threshold increment) on the
      detection on that target. The masking effect decreased as the difference in
      chromaticity between the target and mask increased. This suggests that the
      symmetry detection mechanisms are color selective and only extract local image
      features of a specific chromaticity. 

PMID- 24463696
TI  - Influence of human T-lymphotropic virus type 1 coinfection on the development of
      hepatocellular carcinoma in patients with hepatitis C virus infection.
AB  - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) may worsen the clinical
      course of hepatitis C virus (HCV) infection. The aim of this study was to
      investigate whether HTLV-1 coinfection influences the clinical characteristics of
      patients with HCV infection. METHODS: This retrospective study included 523
      consecutive patients from January 2001 to December 2010 with chronic liver
      disease due to HCV infection, in whom serum anti-HTLV-1 antibodies were examined.
      Among these patients, 265 were diagnosed with hepatocellular carcinoma (HCC).
      RESULTS: The seroprevalence of anti-HTLV-1 antibodies was significantly higher in
      patients with HCC (21.1%) than those without HCC (10.5%, P = 0.001). This
      significant difference was observed in female patients (29.5 vs. 8.5%, P <
      0.001), but not in male patients (16.5 vs. 12.9%, P = 0.501). In multivariate
      analysis, anti-HTLV-1 antibody positivity was independently associated with HCC
      in female patients [odds ratio (OR), 5.029; 95% confidence interval (95% CI),
      1.760-14.369; P = 0.003], in addition to age (>=65 years; OR, 10.297; 95% CI,
      4.322-24.533; P < 0.001), platelet count (<15 * 10(4)/MUL; OR, 2.715; 95% CI,
      1.050-7.017; P = 0.039), total bilirubin (>=1 mg/dL; OR, 3.155; 95% CI, 1.365
      7.292; P = 0.007), and total cholesterol (<=160 mg/dL; OR, 2.916; 95% CI, 1.341
      6.342; P = 0.007). In contrast, HTLV-1 coinfection was not associated with HCC in
      male patients, although age, alcohol consumption, platelet count, and albumin
      were independently associated with HCC. CONCLUSIONS: HTLV-1 coinfection may
      contribute to the development of HCC in patients with chronic HCV infection,
      especially in females.

PMID- 24463697
TI  - Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non
      alcoholic fatty liver disease.
AB  - OBJECTIVES: This study evaluates the value of Gd-EOB-DTPA-enhanced MRI for
      diagnosis and staging of non-alcoholic fatty liver disease (NAFLD) in an animal
      model by T1 relaxation time measurement. METHODS: Thirty-four rabbits were
      divided into the control group (n = 10) and NAFLD group, which was split into
      four groups (n = 6) with a high-fat diet for an interval of 3 weeks. A dual flip
      angle was performed before and at the hepatobiliary phase (HBP). T1 relaxation
      times of the liver parenchyma and the decrease rate (?%) were calculated.
      Histological findings according to semi-quantitative scoring of steatosis,
      activity and fibrosis were the standard of reference. RESULTS: HBP and ?% T1
      relaxation time measurement showed significant differences between normal and
      NAFLD groups, between non-alcoholic steatohepatitis (NASH) and NAFLD without NASH
      (p = 0.000-0.049), between fibrosis groups (p = 0.000-0.019), but no difference
      between F1 and F2 (p = 0.834). The areas under the receiver operating
      characteristic curves (AUCs) of T1 relaxation time for HBP and ?% were 0.86-0.93
      for the selection of NASH and activity score >=2, and 0.86-0.95 for the selection
      of F >= 1, 2, 3. No significant difference was found for diagnostic performance
      between HBP and ?% T1 relaxation time. CONCLUSIONS: HBP T1 relaxation time
      measurement of Gd-EOB-DTPA-enhanced MRI was useful to evaluate NAFLD according to
      the SAF score. HBP T1 relaxation time measurement was as accurate as ?% T1
      relaxation time. KEY POINTS: * Gd-EOB-DTPA-enhanced MRI could give useful
      information on NAFLD. *HBP T 1 relaxation time measurement was useful for the
      evaluation of NAFLD. * HBP T 1 relaxation time measurement was as accurate as ?%.

PMID- 24463699
TI  - C-H activation: New recipes for biocatalysis.

PMID- 24463698
TI  - Direct nitration and azidation of aliphatic carbons by an iron-dependent
      halogenase.
AB  - Iron-dependent halogenases employ cis-halo-Fe(IV)-oxo (haloferryl) complexes to
      functionalize unactivated aliphatic carbon centers, a capability elusive to
      synthetic chemists. Halogenation requires (i) coordination of a halide anion (Cl(
      ) or Br(-)) to the enzyme's Fe(II) cofactor, (ii) coupled activation of O2 and
      decarboxylation of alpha-ketoglutarate to generate the haloferryl intermediate,
      (iii) abstraction of hydrogen (H*) from the substrate by the ferryl and (iv)
      transfer of the cis halogen as Cl* or Br* to the substrate radical. This
      enzymatic solution to an unsolved chemical challenge is potentially generalizable
      to installation of other functional groups, provided that the corresponding
      anions can support the four requisite steps. We show here that the wild-type
      halogenase SyrB2 can indeed direct aliphatic nitration and azidation reactions by
      the same chemical logic. The discovery and enhancement by mutagenesis of these
      previously unknown reaction types suggest unrecognized or untapped versatility in
      ferryl-mediated enzymatic C-H bond activation. 

PMID- 24463700
TI  - Cotinine concentration in serum correlates with tobacco smoke-induced emphysema
      in mice.
AB  - Secondhand smoke (SHS) has been associated with a variety of adverse health
      outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary
      disease). One way to detect SHS exposure is to measure the concentration of
      cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed
      a method for cotinine analysis by combining micellar electrokinetic
      chromatography with enrichment techniques. We employed the method to measure
      cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12
      or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed
      to room air for the same period. Further, we investigated the morphological
      changes in lungs of mice and observed tobacco smoke induced emphysema. Our
      results indicate that the method can be used to measure cotinine and there is an
      association between the serum cotinine concentration and tobacco smoke-induced
      emphysema in mice. 

PMID- 24463701
TI  - Selective alpha-amination and alpha-acylation of esters and amides via dual
      reactivity of O-acylhydroxylamines toward zinc enolates.
AB  - Selective alpha-amination and alpha-acylation of esters and amides have been
      developed, employing O-acylhydroxylamines as a dually reactive aminating and
      acylating reagent. Treatment of zinc enolates with O-acylhydroxylamines provides
      solely 1,3-dicarbonyl compounds under mild conditions. Introduction of a copper
      catalyst into the system shifts the reactivity entirely, yielding alpha-amination
      products exclusively. 

PMID- 24463702
TI  - P2Y2 receptor activation inhibits the expression of the sodium-chloride
      cotransporter NCC in distal convoluted tubule cells.
AB  - Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal
      nephron. Previous studies suggest that this mechanism may involve the thiazide
      sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl
      reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show
      that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+)
      transients and decreased the expression of NCC at both mRNA and protein levels.
      Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished
      ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced
      decrease of NCC expression. To test whether local variations in the intracellular
      Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed
      the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the
      nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was
      abolished in cells overexpressing cytosolic PV but not in cells overexpressing
      either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a
      firefly luciferase reporter gene strategy, we observed that the activity of NCC
      promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i.
      In contrast, high cytosolic calcium level induced instability of NCC mRNA. We
      conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular
      Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of
      cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the
      decrease of NCC expression occurs, at least in part, via destabilization of its
      mRNA. 

PMID- 24463703
TI  - Reduced excitability of gp130-deficient nociceptors is associated with increased
      voltage-gated potassium currents and Kcna4 channel upregulation.
AB  - Neuropathic pain and pain arising from local inflammation are characterized by
      increased release of inflammatory mediators like interleukin-6 (IL-6) by immune
      cells. The levels of IL-6 is increased in various painfull conditions and
      correlates with the severity of thermal and mechanical hypersensitivity. Deletion
      of the IL-6 signal transducer glycoprotein 130 (gp130) reduces inflammation
      associated with hypersensitivity to thermal and mechanical stimuli. In this
      study, we show that nociceptor-specific deletion of gp130 alters excitability
      parameters that are linked to changes in the potassium conductance. In SNS-gp130(
      /-) sensory neurons, the resting membrane potential was reduced. Moreover the
      repolarization speed of the action potential and afterhypolarization was
      augmented, however, voltage-gated Na(+) and Ca(2+) current were not obviously
      altered. The main difference between gp130-deficient and control neurons was a
      significant increase in the conductance of both delayed rectifier as well as A
      type potassium currents. Taqman RT-PCR analysis revealed significantly higher
      levels of Kcna4 mRNA, encoding A-type Kv1.4 potassium channel, in neuron cultures
      from SNS-gp130(-/-) versus control mice, which may account for the
      electrophysiological data. No difference in other voltage-gated ion channel mRNAs
      was observed. The present data show for the first time increased A-type K(+)
      currents and expression of voltage-gated potassium channel Kcna4 (Kv1.4) in SNS
      gp130(-/-) nociceptors. This suggests that gp130 acts as a break for the
      expression of potassium channels and important regulator hub for nociceptor
      excitability.

PMID- 24463705
TI  - ICF-DOC: the ICF dedicated checklist for evaluating functioning and disability in
      people with disorders of consciousness.
AB  - Clinicians need a comprehensive description of patients' functioning state to
      capture the complex interaction between symptoms and environmental factors, and
      to determine the actual level of functioning in patients in a vegetative state or
      a minimally conscious state. The aim of this study is to develop an International
      Classification of Functioning, Disability, and Health (ICF) checklist for
      patients with disorders of consciousness (DOC) so as to capture and describe,
      with a tailored list of categories, the most common health, disability, and
      functioning issues of adult patients with DOC. The WHO ICF checklist was used as
      a basis for collecting data. This was an observational, cross-sectional,
      multicenter study conducted in 69 Italian centers. Specific methodological
      procedures were used to identify the most appropriate categories for DOC patients
      to be added to or deleted from the ICF checklist so as to develop the ICF-DOC
      checklist. A total of 566 adult patients were enrolled: 398 in a vegetative state
      and 168 in a minimally conscious state. A total of 127 ICF categories reached the
      threshold of 20% concerning the presence of a problem: 37 categories from the
      body functions chapter, 13 from the body structures chapter, 46 from the
      activities and participations chapter, and 31 from the environmental factors
      chapter. ICF categories identified in this study can be useful guidelines for
      clinicians and researchers to collect data on functioning and disability of adult
      patients with DOC. The new ICF-DOC checklist allows monitoring of the effects of
      interventions on functional areas and possible changes in each patient in follow
      up studies. 

PMID- 24463704
TI  - T-type Ca2+ channels and the urinary and male genital tracts.
AB  - T-type Ca(2+) channels are widely expressed throughout the urinary and male
      genital tracts, generally alongside L-type Ca(2+) channels. The use of
      pharmacological blockers of these channels has suggested functional roles in all
      regions, with the possible exception of the ureter. Their functional expression
      is apparent not just in smooth muscle cells but also in interstitial cells that
      lie in close proximity to muscle, nerve and epithelial components of these
      tissues. Thus, T-type Ca(2+) channels can contribute directly to modulation of
      muscle function and indirectly to changes of epithelial and nerve function. T
      type Ca(2+) channel activity modulates phasic contractile activity, especially in
      conjunction with Ca(2+)-activated K(+) channels, and also to agonist-dependent
      responses in different tissues. Upregulation of channel density occurs in
      pathological conditions associated with enhanced contractile responses, e.g.
      overactive bladder, but it is unclear if this is causal or a response to the
      pathological state. Moreover, T-type Ca(2+) channels may have a role in the
      development of prostate tumours regulating the secretion of mitogens from
      neuroendocrine cells. Although a number of selective channel blockers exist,
      their relative selectivity over L-type Ca(2+) channels is often low and makes
      evaluation of T-type Ca(2+) channel function in the whole organism difficult. 

PMID- 24463707
TI  - Possible clinical aspects of a linkage of preceding weight loss and heart
      failure.

PMID- 24463706
TI  - Interfacial interactions between natural RBC membranes and synthetic polymeric
      nanoparticles.
AB  - The unique structural features and stealth properties of a recently developed red
      blood cell membrane-cloaked nanoparticle (RBC-NP) platform raise curiosity over
      the interfacial interactions between natural cellular membranes and polymeric
      nanoparticle substrates. Herein, several interfacial aspects of the RBC-NPs are
      examined, including completeness of membrane coverage, membrane sidedness upon
      coating, and the effects of polymeric particles' surface charge and surface
      curvature on the membrane cloaking process. The study shows that RBC membranes
      completely cover negatively charged polymeric nanoparticles in a right-side-out
      manner and enhance the particles' colloidal stability. The membrane cloaking
      process is applicable to particle substrates with a diameter ranging from 65 to
      340 nm. Additionally, the study reveals that both surface glycans on RBC
      membranes and the substrate properties play a significant role in driving and
      directing the membrane-particle assembly. These findings further the
      understanding of the dynamics between cellular membranes and nanoscale substrates
      and provide valuable information toward future development and characterization
      of cellular membrane-cloaked nanodevices. 

PMID- 24463708
TI  - Fractional flow reserve with dobutamine challenge and coronary microvascular
      endothelial dysfunction in symptomatic myocardial bridging.
AB  - BACKGROUND:  Myocardial bridging (MB) results in compression of the coronary
      artery lumen in systole, extending into diastole with resultant hemodynamic
      alternation as reflected by fractional flow reserve (FFR). MB has also been
      associated with coronary endothelial dysfunction. The objective of this study was
      to investigate relationship between FFR with dobutamine challenge and coronary
      microvascular endothelial dysfunction in symptomatic MB. METHODS AND RESULTS: 
      Seventeen consecutive patients who had cardiac catheterization assessment of MB
      were enrolled. The patients were divided into 2 groups according to normal (%
      increase in coronary blood flow [%CBF] >=50%, n=7) or impaired (%CBF <50%, n=10)
      coronary microvascular endothelial function assessed on vasoreactivity in the
      coronary artery with intracoronary infusion of acetylcholine (Ach). Myocardial
      ischemia was then assessed using FFR at rest and during i.v. dobutamine infusion
      challenge across the MB with intracoronary pressure wires. FFR was significantly
      decreased at peak dobutamine infusion compared to at rest in the impaired group
      (0.85+/-0.06 vs. 0.91+/-0.05, P=0.001), but not in the normal group (0.93+/-0.05
      vs. 0.91+/-0.07, P=0.618). Both FFR at rest and at peak dobutamine infusion had a
      positive correlation with %CBF by Ach in the impaired group (r(2)=0.46, P=0.030;
      r(2)=0.52, P=0.018, respectively). CONCLUSIONS:  Microvascular endothelial
      dysfunction was associated with decreased FFR at peak dobutamine stress in
      patients with symptomatic MB. 

PMID- 24463709
TI  - Analysis of anticoagulant therapy by unfractionated heparin during pregnancy
      after mechanical valve replacement.
AB  - BACKGROUND:  Consensus has not been reached about the anticoagulant therapy to be
      used during pregnancy after mechanical valve replacement. Warfarin is a fetal
      toxicant, so we retrospectively examined anticoagulant therapy using
      unfractionated heparin. METHODS AND RESULTS:  Pregnancy after mechanical valve
      replacement occurred in 25 cases between 1983 and 2011. Targeted therapy using
      unfractionated heparin was administered in 9 pregnancies, which were divided into
      3 groups: Group I received subcutaneous administration of heparin and APTT was
      measured twice weekly; Group II received heparin by constant rate infusion (CRI)
      and APTT was measured twice weekly; Group III received CRI of heparin and APTT
      was measured daily. Maternal complications consisted of valve thrombosis and
      perinatal bleeding in 1 pregnancy (Group I), intracranial hemorrhage in 2
      pregnancies (Group II), and valve thrombosis and perinatal bleeding in 1
      pregnancy (Group III). Two infants died in the neonatal period. CONCLUSIONS: 
      Each group showed a high rate of maternal complications, so a review of current
      anticoagulant treatment strategies is necessary.

PMID- 24463710
TI  - Effects of the preparation method and humic-acid modification on the mobility and
      contaminant-mobilizing capability of fullerene nanoparticles (nC60).
AB  - Colloidal fullerene nanoparticles (nC60) in aquatic environments may
      significantly affect the transport and risks of hydrophobic organic contaminants
      by serving as a contaminant carrier. The objective of this study was to
      understand how the combined variables of the preparation method and natural
      organic matter modification of nC60 might affect the mobility and contaminant
      mobilizing capability of nC60, by affecting the physicochemical properties of
      nC60. We found that an nC60 sample prepared by sonicating C60 powder in deionized
      water (son_nC60) was much less mobile in saturated sandy soil columns than an
      nC60 sample prepared by solvent-exchanging from toluene to water (tol_nC60),
      because son_nC60 was considerably larger in size. However, son_nC60 exhibited
      greater capability to bind 2,2',5,5'-polychlorinated biphenyl (PCB), likely
      because its loosely packed structures rendered more pore spaces, which were
      favorable adsorption sites for PCB. Forming nC60 samples in Suwannee River humic
      acid (SRHA) solution (instead of deionized water) only moderately affected the
      mobility of nC60, but had very significant effects on the contaminant-binding
      capability of nC60, especially when nC60 was prepared using the solvent exchange
      method. Adding SRHA after the formation of nC60 had varied effects on the
      mobility and contaminant-binding capability of nC60, but the fundamental
      mechanism seems to be linked to how and to what extent SRHA had affected the
      aggregation/packing of C60 monomers. An important environmental implication is
      that nC60 formed under different environmental conditions might have vastly
      different effects on contaminant transport and risks. 

PMID- 24463711
TI  - Primary clinical manifestation of systemic amyloidosis in the central nervous
      system.

PMID- 24463712
TI  - Smoking cessation and subsequent weight change.
AB  - INTRODUCTION: People who quit smoking tend to gain more weight over time than
      those who continue to smoke. Previous research using clinical samples of smokers
      suggests that quitters typically experience a weight gain of approximately 5 kg
      in the year following smoking cessation, but these studies may overestimate the
      extent of weight gain in the general population. The existing population-based
      research in this area has some methodological limitations. METHODS: We assessed a
      cohort of individuals born in Dunedin, New Zealand, between 1972-1973 at regular
      intervals from age 15 to 38. We used multiple linear regression analysis to
      investigate the association between smoking cessation at ages 21 years to 38
      years and subsequent change in body mass index (BMI) and weight, controlling for
      baseline BMI, socioeconomic status, physical activity, alcohol use, and parity
      (women). RESULTS: Smoking status and outcome data were available at baseline and
      at follow-up for 914 study members. People who smoked at age 21 and who had quit
      by age 38 had a BMI on average 1.5 kg/m(2) greater than those who continued to
      smoke at age 38. This equated to a weight gain of approximately 5.7 kg in men and
      5.1 kg in women above that of continuing smokers. However, the weight gain
      between age 21 and 38 among quitters was not significantly different to that of
      never-smokers. CONCLUSIONS: The amount of long-term weight gained after quitting
      smoking is likely to be lower than previous estimates based on research with
      clinical samples. On average, quitters do not experience greater weight gain than
      never-smokers.

PMID- 24463713
TI  - [The role of pathology in the diagnostics of CUP syndrome].
AB  - Cancers of unknown primary (CUP) origin account for 2-3 % of all malignancies in
      Germany and represent a heterogeneous, often aggressive and clinically
      challenging group of tumors with early metastatic dissemination for which a
      standardized diagnostic work-up initially fails to identify the primary site of
      origin at the time of diagnosis. This article reviews the options and challenges
      of tissue-based conventional as well as molecular diagnostic procedures to
      categorize this heterogeneous group of neoplasms. The role of pathology in the
      diagnostics of CUP syndrome is described as part of a multidisciplinary effort
      involving oncologists, surgeons and radiologists with the ultimate goal of
      assisting clinical reasoning and decision-making. 

PMID- 24463714
TI  - [Visualization of subtle temporal bone structures. Comparison of cone beam CT and
      MDCT].
AB  - PURPOSE: The purpose of this study was to compare the visualization of subtle,
      non-pathological temporal bone structures on cone beam computed tomography (CBCT)
      and multi-detector computed tomography (MDCT) in vivo. MATERIALS AND METHODS:
      Temporal bone studies of images from 38 patients archived in the picture
      archiving and communication system (PACS) were analyzed (slice thickness MDCT 0.6
      mm and CBCT 0.125 mm) of which 23 were imaged by MDCT and 15 by CBCT using
      optimized standard protocols. Inclusion criteria were normal radiological
      findings, absence of previous surgery and anatomical variants. Images were
      evaluated blind by three trained observers. Using a five-point scale the
      visualization of ten subtle structures of the temporal bone was analyzed.
      RESULTS: Subtle middle ear structures showed a tendency to be more easily
      distinguishable by CBCT with significantly better visualization of the tendon of
      the stapedius muscle and the crura of the stapes on CBCT (p = 0.003 and p =
      0.033, respectively). In contrast, inner ear components, such as the osseus
      spiral lamina and the modiolus tended to be better detectable on MDCT, showing
      significant differences for the osseous spiral lamina (p = 0.001). The interrater
      reliability was 0.73 (Cohen's kappa coefficient) and intraobserver reliability
      was 0.89. CONCLUSION: The use of CBCT and MDCT allows equivalent and excellent
      imaging results if optimized protocols are chosen. With both imaging techniques
      subtle temporal bone structures could be visualized with a similar degree of
      definition. In vivo differences do not seem to be as large as suggested in
      several previous studies.

PMID- 24463715
TI  - Role of transcription and enzyme activities in redistribution of carbon and
      electron flux in response to N2 and H2 sparging of open-batch cultures of
      Clostridium thermocellum ATCC 27405.
AB  - Growth, end-product synthesis, enzyme activities, and transcription of select
      genes associated with the "malate shunt," pyruvate catabolism, H2 synthesis, and
      ethanol production were studied in the cellulolytic anaerobe, Clostridium
      thermocellum ATCC 27405, during open-batch fermentation of cellobiose to
      determine the effect of elevated N2 and H2 gas sparging on metabolism using a 14
      L fermenter with a 7-L working volume. The metabolic shift from acetate, H2, and
      CO2 to ethanol and formate in response to high H2 versus high N2 sparging (20 mL
      s(-1)) was accompanied by (a) a 2-fold increase in nicotinamide adenine
      dinucleotide (NADH)-dependent alcohol dehydrogenase (Adh) activity, (b) a 10-fold
      increase in adhE transcription, and (c) a 3-fold decrease in adhZ transcription.
      A similar, but less pronounced, metabolic shift was also observed when the rate
      of N2 sparging was decreased from 20 to 2 mL s(-1), during which (a) NADH
      dependent ADH and pyruvate: ferredoxin oxidoreductase (PFOR) activities increased
      by ~1.5-fold, (b) adhY transcription increased 6-fold, and (c) transcription of
      selected pfor genes increased 2-fold. Here we demonstrate that transcription of
      genes involved in ethanol metabolism is tightly regulated in response to gas
      sparging. We discuss the potential impacts of dissolved H2 on electron carrier
      (NADH, NADPH, ferredoxin) oxidation and how these electron carriers can redirect
      carbon and electron flux and regulate adhE transcription.

PMID- 24463716
TI  - Directed evolution of nitrobenzene dioxygenase for the synthesis of the
      antioxidant hydroxytyrosol.
AB  - Nitrobenzene dioxygenase (NBDO) is known to add both atoms of molecular oxygen to
      the aromatic ring of nitrobenzene to form catechol. It is assembled by four
      subunits of which the alpha subunit is responsible for catalysis. As an oxidizing
      enzyme, it has a potential use in the detoxification of industrial waste and the
      synthesis of pharmaceuticals and food ingredients; however, not much work has
      been done studying its structure-function correlations. We used several protein
      engineering approaches (neutral drift libraries, random libraries, two types of
      focused libraries, and family shuffling) to engineer NBDO for the production of
      the highly potent antioxidant, hydroxytyrosol (HTyr), from the substrate 3
      nitrophenethyl alcohol (3NPA). We obtained a triple mutant, F222C/F251L/G253D,
      which is able to oxidize 3NPA 375-fold better than wild type with a very high
      regioselectivity. In total, we identified four positions which are important for
      acquisition of new specificities, of which only one is well-known and studied.
      Based on homology modeling, it is suggested that these mutations increase
      activity by vacating extra space within the active site for the larger substrate
      and also by hydrogen bonding to the substrate. The best variant had acquired a
      stabilizing mutation which was beneficial only in this mutant. Thus, we have
      achieved two goals, the first is the enzymatic production of HTyr, and the second
      is valuable information regarding the structure-function correlations of NBDO. 

PMID- 24463717
TI  - Highly efficient expression of functional recombinant human keratinocyte growth
      factor 1 and its protective effects on hepatocytes.
AB  - Three forms of recombinant human keratinocyte growth factor 1 (rhKGF1) with or
      without the native signal peptide or a 23-amino acid truncation were expressed in
      Spodoptera frugiperda 9 (Sf9) cells by designing with insect codon usage.
      Immunoblotting demonstrated that these rhKGF1 proteins were recognized by a human
      anti-KGF1 antibody. The multiplicity of infection and timing of harvest had a
      significant effect on protein yield, protein quality, and cytotoxicity. Our
      results indicated that the native signal peptide directed KGF1 secretion from
      insect cells, reaching a maximum at 60 h postinfection. Although secretion of
      rhKGF1194 was less efficient than that of rhKGF1163 and rhKGF1140, protein
      secretion is an attractive pathway for simple purification of biologically active
      rhKGF1 at a high yield. Moreover, the sizes of rhKGF1194 and rhKGF1163 were
      similar (20 kDa), suggesting that the signal peptide may be recognized and
      removed in Sf9 cells. A 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium
      bromide assay was used to analyze the biological function of rhKGF1, indicating
      that the three forms of rhKGF1 had a similar mitogenic function in BaF3 cells.
      Furthermore, to elucidate the effect of rhKGF1 on cytoprotection of liver cells,
      we used KGF1 pretreatment of an acute liver injury model. The results indicated
      that rhKGF1 prevented necrosis and apoptosis of CCl4-treated HL7702 cells in
      vitro and in vivo. These results suggest that KGF1 may be a candidate therapeutic
      drug for acute liver injury. 

PMID- 24463718
TI  - Provider-initiated HIV testing and counselling for TB in low HIV prevalence
      settings: is it worthwhile?
AB  - BACKGROUND: We assessed the HIV-positive yield of offering provider-initiated HIV
      testing and counselling (PITC) for TB and the costs, in Madagascar, which has a
      low HIV prevalence and a high TB burden. METHODS: A cross-sectional study of
      routinely collected records from January 2010 to June 2011. RESULTS: A total of
      37 596 TB patients were registered in 205 TB centres. HIV testing was available
      in 95 (46%) of centres where 7524 (40%) of those offered testing accepted it.
      Only 35 (0.5%) individuals were found HIV positive. Initial costs were about
      US$1.4 million and annual recurrent costs about US$0.1 million. CONCLUSION: There
      are concerns of cost investment for countrywide introduction of PITC in a low HIV
      prevalence setting.

PMID- 24463719
TI  - Anti-Trypanosoma cruzi antibody detection in eastern Andalusia (Spain).
AB  - BACKGROUND: Chagas disease caused by the protozoan haemoflagellate Trypanosoma
      cruzi is no longer found exclusively in Latin America; the disease is occurring
      in Europe, and Spain is the country with the highest prevalence. METHODS: Our aim
      was to detect anti-T. cruzi antibodies in blood donors from southeast Spain, and
      we performed eight serological diagnostic assays on each of 550 blood samples
      collected in March-June 2010. Two in-house ELISA methods were used to test
      against a parasite lysate (ELISA-H) and the semi-purified superoxide dismutase
      excreted by T. cruzi (ELISA-SODe); we also used the Western blot technique
      against the same antigen (WB-SODe), indirect immunofluorescence (IFA) and four
      commercial tests. RESULTS: The serological test results showed a range of
      seroprevalence values, the lowest being 1.1%, determined by IFA and two
      commercial tests (Ab rapid and Chagascreen); other values were: 1.3% (commercial
      ELISA [Chagas ELISA IgG+IgM]); 2.1% (immunochromatographic test [Stick Chagas]);
      2.7% (ELISA-H); 4.0% (WB-SODe); and 4.2%, the highest value (ELISA-SODe).
      CONCLUSIONS: The excellent specificity of SODe antigen for the detection of
      antibodies to T. cruzi in donors lead us to affirm that the serological test
      performed with this biomarker could provide a useful screening and confirmatory
      test method for cases of Chagas disease.

PMID- 24463720
TI  - Radioactivity in drinking water supplies in Western Australia.
AB  - Radiochemical analysis was carried out on 52 drinking water samples taken from
      public outlets in the southwest of Western Australia. All samples were analysed
      for Ra-226, Ra-228 and Pb-210. Twenty five of the samples were also analysed for
      Po-210, and 23 were analysed for U-234 and U-238. Ra-228 was found in 45 samples
      and the activity ranged from <4.000 to 296.1 mBq L(-1). Ra-226 was detected in
      all 52 samples and the activity ranged from 3.200 to 151.1 mBq L(-1). Po-210 was
      detected in 24 samples and the activity ranged from 0.000 to 114.2 mBq L(-1).
      These data were used to compute the annual radiation dose that persons of
      different age groups and also for pregnant and lactating females would receive
      from drinking this water. The estimated doses ranged from 0.001 to 2.375 mSv y(
      1) with a mean annual dose of 0.167 mSv y(-1). The main contributing
      radionuclides to the annual dose were Ra-228, Po-210 and Ra-226. Of the 52
      drinking water samples tested, 94% complied with the current Australian Drinking
      Water Guidelines, while 10% complied with the World Health Organization's
      radiological guidelines which many other countries use. It is likely that these
      results provide an overestimate of the compliance, due to limitations, in the
      sampling technique and resource constraints on the analysis. Because of the
      increasing reliance of the Western Australian community on groundwater for
      domestic and agricultural purposes, it is likely that the radiological content of
      the drinking water will increase in the future. Therefore there is a need for
      further monitoring and analysis in order to identify problem areas. 

PMID- 24463721
TI  - Uptake of some radionuclides by woody plants growing in the rainforest of Western
      Ghats in India.
AB  - Transfer of the naturally occurring radionuclides (238)U, (232)Th, and (40)K, and
      the fallout radionuclide (210)Po to different wild plant species in the
      rainforest of Western Ghats was analyzed. A number of physiologically different
      plants from the top storey and understorey, such as shrubs and epiphytes, were
      compared. The concentrations of these radionuclides in the plants and soil were
      measured using a gamma ray spectrometer and an alpha counter, and were found to
      vary widely within plants and between species. The soil-plant ratios also varied
      between species while Elaeocarpus oblongus and epiphytic plants exhibited
      preferential uptake of these radionuclides. As a result, the dust particles
      trapped in the root systems of epiphytes could be used as bioindicators of
      fallout radionuclides in the Western Ghats. 

PMID- 24463722
TI  - Application of (234)U/(238)U activity ratios to investigations of subterranean
      groundwater discharge in the Cadiz coastal area (SW Spain).
AB  - The activity ratios of (234)U/(238)U were used to investigate processes of
      subterranean groundwater discharge into coastal marine waters in a study location
      at Bay of Cadiz (southwest Spain). Marine waters in the bay and surrounding open
      ocean exhibited U concentrations of 3.4 +/- 0.1 MUg/L and activity ratios of 1.15
      +/- 0.01, in agreement with the expected composition of seawater ((234)U/(238)U
      activity ratio = 1.148 +/- 0.002). Three water samples obtained from the
      discharge zone of the Guadalete River exhibited activity ratios of 1.17-1.22
      along with slightly lower U concentrations compared to seawater, which is likely
      due to mixing between seawater and a groundwater end-member. One possible source
      of groundwater was characterized by sampling and analyzing a well water sample
      collected in the neighboring village of El Puerto de Santa Maria; this water
      sample exhibited an activity ratio of 1.34 +/- 0.03 and a U concentration of 1.22
      MUg/L. Water from the Guadelete River estuarine zone can be explained to result
      from a two-component mixture of seawater and groundwater from the El Puerto de
      Santa Maria well; however, if there are several groundwater reservoirs with
      different U activity ratios that discharge to the coastal water, then, it may be
      difficult and more studies are being conducted to address this issue. 

PMID- 24463723
TI  - Molecular characteristics of vancomycin-resistant Enterococcus faecium from a
      tertiary care hospital in Chengdu, China: molecular characteristics of VRE in
      China.
AB  - The aim of this study was to characterize vancomycin-resistant Enterococcus
      faecium (VREfm) isolates phenotypically and molecularly, and investigate
      associations between the virulence factors enterococcal surface protein (esp),
      hyaluronidase (hyl), and collagen adhesin (acm) and colonization/infection. A
      total of 126 E. faecium [66 VREfm and 60 vancomycin-susceptible (VSEfm)] were
      collected in West China Hospital. Nine E. faecium isolates (7 VREfm and 2 VSEfm)
      were selected at random for comparative study in a large region from China.
      Minimum inhibitory concentrations (MICs) were measured by Etest and agar
      dilution, vancomycin resistance genes (vanA, vanB, and vanC) and virulence genes
      (esp, acm, and hyl) were detected by polymerase chain reaction (PCR). Thirty-four
      VREfm underwent repetitive sequence-based PCR (rep-PCR) and multi-locus sequence
      typing (MLST). One linezolid-resistant isolate (MIC = 8 MUg/ml) was found; none
      were tigecycline resistant. All 73 VREfm (28 infective strains and 45 intestinal
      colonizers) had the vanA gene and VanA phenotype. Positivity for esp, hyl, and
      acm in VREfm was 79.5, 46.6, and 86.3%, respectively, which was higher than in
      VSEfm (54.8, 27.4, and 56.5%, respectively). Among VSEfm, positivity for acm in
      isolates from pleural or cerebrospinal fluid (84.6%) was higher than that from
      blood (32.4%). There were 11 rep-PCR types (similarity >95%) and MLST revealed
      nine sequence types (STs) among the selected isolates. Most VREfm and all VSEfm
      belonged to clonal complex 17. A new ST was found, with allele sequence (15, 1,
      38, 1, 1, 1, 1). In China, most VREfm seem to belong to the classical nosocomial
      CC17 clone, and many of them have acquired virulence genes, further strengthening
      a hospital-adapted type.

PMID- 24463724
TI  - Time trends of viral meningitis among young adults in Israel: 1978-2012.
AB  - Viral meningitis (VM) is a medical condition of public health concern, as it is a
      common sporadic and epidemic illness. However, there is limited data on the
      epidemiology of VM. The purpose of this study was to analyze long-term and
      seasonal trends of VM in a young adult military population. VM is a obligatory
      notifiable disease in the Israel Defense Forces. For the present study, the
      archives of the Army Health Branch were reviewed for all cases of VM from January
      1, 1978 to December 31, 2012, and the annual, monthly, and seasonal rates were
      calculated. The annual incidence over the 35-year period showed a high peak every
      3-5 years followed by a quiescent period of 2-3 years, reaching as high as 58.4
      per 100,000 in 1980 and as low as 3.0 per 100,000 in 2005. This cyclic pattern
      has diminished over the last decade, reflected by a decline in mean incidence
      (10.46 per 100,000 in 2003-2012 compared to 19.79 per 100,000 in 1978-2002).
      Average monthly rates ranged from 1.0 cases per 100,000 soldiers in
      January/February to 2.2 per 100,000 in July/August. The difference in average
      rates between winter (1.2 cases per 100,000) and summer (1.9 cases per 100,000)
      was statistically significant (p < 0.001). Analysis of the long-term epidemiology
      of VM shows an epidemic pattern, with predominance in the warmer months.
      Identifying viral causes of meningitis may spare patients unnecessary treatment
      while prompting the introduction of public health interventions and control
      measures, especially in crowded settings.

PMID- 24463725
TI  - A most forward-looking academy.

PMID- 24463728
TI  - The impact of advanced heart failure on social, psychological and existential
      aspects and personhood.
AB  - BACKGROUND: Heart failure is a common cause of death and causes significant
      morbidity in its advanced stage. As the illness progresses, lack of physical
      health may overshadow psychological, social and existential distress. AIMS: To
      explore the impact of advanced heart failure on other aspects of the patients'
      lives. METHODS: We undertook a secondary analysis of interview data generated for
      a qualitative longitudinal study looking at the experiences of patients with
      advanced heart failure, and their family and professional carers. A sub set of
      patient, family and professional carer interview transcripts was selected for
      thematic analysis. The sample was chosen to reflect a range of age, gender and
      social situations. RESULTS: Eighteen transcripts from five cases were examined.
      Three key themes were identified: 1) social isolation; 2) psychological issues
      and coping strategies; and 3) existential concerns. CONCLUSIONS: Psychosocial and
      existential issues are important aspects of the lives of patients suffering from
      heart failure. Holistic management should encompass an awareness of exploration
      and support for these dimensions.

PMID- 24463729
TI  - The effects of a counselling intervention on lifestyle change in people at risk
      of cardiovascular disease.
AB  - BACKGROUND: The study assessed the effects of a counselling intervention on
      lifestyle changes in certain-aged people at risk of cardiovascular disease.
      DESIGN AND METHODS: This was an intervention study at baseline and six- and 12
      month follow-ups. The participants were 40 years old (n= 53 at baseline, n=33 at
      six months and n=34 at 12 months). The main outcomes were cardiovascular health
      parameters, such as weight, BMI, waist circumference, blood pressure, cholesterol
      (total, high density lipoprotein, low density lipoprotein), blood glucose, and
      self-assessed and reported lifestyle and adherence to lifestyle changes. The
      counselling intervention was Internet-based and carried out via Skype or face-to
      face in small groups (on average, six participants). RESULTS: There were
      statistically significant differences between the baseline and the 12-month
      follow-up with respect to the consumption of fat and snacks. Some positive
      cardiovascular health improvements were detected between baseline and six months,
      but not as clearly between baseline and 12 months. The participants reported
      having a healthier diet at 12 months than at baseline. At 12 months, BMI
      measurements indicated that all participants were overweight (mean BMI 29.8), but
      according to the self-assessed data, only 25% considered themselves to be so.
      CONCLUSIONS: Changes in lifestyle were detected as a result of the intervention.
      These lifestyle changes may improve cardiovascular health in the long term.
      Discrepancies were found between the measured indicators of cardiovascular health
      and information obtained from questionnaires and diary records. In order to
      achieve sustainable lifestyle changes, long-term support is required.

PMID- 24463730
TI  - Assessment of energy-saving strategies and operational costs in full-scale
      membrane bioreactors.
AB  - The energy-saving strategies and operational costs of stand-alone, hybrid, and
      dual stream full-scale membrane bioreactors (MBRs) with capacities ranging from
      1100 to 35,000 m(3) day(-1) have been assessed for seven municipal facilities
      located in Northeast Spain. Although hydraulic load was found to be the main
      determinant factor for the energy consumption rates, several optimisation
      strategies have shown to be effective in terms of energy reduction as well as
      fouling phenomenon minimization or preservation. Specifically, modifications of
      the biological process (installation of control systems for biological aeration)
      and of the filtration process (reduction of the flux or mixed liquor suspended
      solids concentration and installation of control systems for membrane air
      scouring) were applied in two stand-alone MBRs. After implementing these
      strategies, the yearly specific energy demand (SED) in flat-sheet (FS) and hollow
      fibre (HF) stand-alone MBRs was reduced from 1.12 to 0.71 and from 1.54 to 1.12
      kW h(-1) m(-3), respectively, regardless of their similar yearly averaged
      hydraulic loads. The strategies applied in the hybrid MBR, namely, buffering the
      influent flow and optimisation of both biological aeration and membrane air
      scouring, reduced the SED values by 14%. These results illustrate that it is
      possible to apply energy-saving strategies to significantly reduce MBR
      operational costs, highlighting the need to optimise MBR facilities to reconsider
      them as an energy-competitive option. 

PMID- 24463731
TI  - Valorization of sugarcane bagasse ash: producing glass-ceramic materials.
AB  - Some aluminosilicates, for example mullite and wollastonite, are very important
      in the ceramic and construction industries. The most significant glass-ceramic
      for building applications has wollastonite as the main crystal phase. In this
      work we report on the use of sugarcane bagasse ash (SCBA) to produce glass
      ceramics with silicates as the major crystalline phases. The glasses (frits) were
      prepared by mixing ash, limestone (calcium and magnesium carbonates) and
      potassium carbonate as the fluxing agent. X-ray fluorescence was used to
      determine the chemical composition of the glasses and their crystallization was
      assessed by using thermal analysis (DTA/DSC/TGA) and X-ray diffraction. The
      results showed that glass-ceramic material can be produced with wollastonite as
      the major phase, at a temperature lower than 900  degrees C. 

PMID- 24463732
TI  - Removal of natural organic matter by titanium tetrachloride: The effect of total
      hardness and ionic strength.
AB  - This study is the first attempt to investigate the effect of total hardness and
      ionic strength on coagulation performance and the floc characteristics of
      titanium tetrachloride (TiCl4). Membrane fouling under different total hardness
      and ionic strength conditions was also evaluated during a coagulation
      ultrafiltration (C-UF) hybrid process. Coagulation experiments were performed
      with two simulated waters, using humic acid (HA, high molecular weight) and
      fulvic acid (FA, relatively low molecular weight), respectively, as model natural
      organic matter (NOM). Results show that both particle and organic matter removal
      can be enhanced by increasing total hardness and ionic strength. Floc
      characteristics were significantly influenced by total hardness and ionic
      strength and were improved in terms of floc size, growth rate, strength,
      recoverability and compactness. The results of the UF tests show that the pre
      coagulation with TiCl4 significantly improves the membrane permeate fluxes. Under
      different total hardness and ionic strength conditions, the membrane permeate
      flux varied according to both NOM and floc characteristics. The increase in total
      hardness and ionic strength improved the membrane permeate flux in the case of HA
      simulated water treatment. 

PMID- 24463733
TI  - Performance analysis of CO(2) emissions and energy efficiency of metal industries
      in China.
AB  - Nonferrous metal industries play an important role in China's national economy
      and are some of the country's largest energy consumers. To better understand the
      nature of CO(2) emissions from these industries and to further move towards low
      carbon development in this industry sector, this study investigates the CO(2)
      emissions of 12 nonferrous metal industries from 2003 to 2010 based on their life
      cycle assessments. It then classifies these industries into four "emission
      efficiency" types through cluster analysis. The results show that (1) the
      industrial economy and energy consumption of China's nonferrous metal industries
      have grown rapidly, although their recent energy consumption rate shows a
      declining trend. (2) The copper, aluminum, zinc, lead, and magnesium industries,
      classified as high-emission industries, are the main contributors of CO(2)
      emissions. The results have implications for policy decisions that aim to enhance
      energy efficiency, particularly for promoting the transformation of low
      efficiency industries to high-efficiency ones. The study also highlights the
      important role of policy development in technological innovations, optimization,
      and upgrades, the reduction of coal proportion in energy consumption, and the
      advancement of new energy sources.

PMID- 24463734
TI  - Ectopic A-lattice seams destabilize microtubules.
AB  - Natural microtubules typically include one A-lattice seam within an otherwise
      helically symmetric B-lattice tube. It is currently unclear how A-lattice seams
      influence microtubule dynamic instability. Here we find that including extra A
      lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of
      dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by
      >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice
      seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet
      have increased catastrophe frequencies at both ends. Furthermore, binding B
      lattice GDP microtubules to a rigor kinesin surface stabilizes them against
      shrinkage, whereas microtubules with extra A-lattice seams are stabilized only
      slightly. Our data suggest that introducing extra A-lattice seams into dynamic
      microtubules destabilizes them by destabilizing their GTP caps. On this basis, we
      propose that the single A-lattice seam of natural B-lattice MTs may act as a
      trigger point, and potentially a regulation point, for catastrophe. 

PMID- 24463737
TI  - How does carbon nanoring deform to spiral induced by carbon nanotube?
AB  - Molecular dynamics (MD) simulations have been performed on the interaction
      between carbon nanoring (CNR) and single-wall carbon nanotube (SWCNT). The
      results show that, the CNR can spontaneously insert into the hollow interior of
      the SWCNTs to form a DNA-like double-helix, or collapse to a linked double
      graphitic nanoribbon and wrap in a helical manner around a tube. Further analyses
      of energy components show that this unique phenomenon is the result of the Van
      der Waals interaction. The spiral configuration of the CNR takes the least amount
      of energy and achieves the maximum occupancy. The sizes of CNR and SWCNT should
      meet the required conditions to guarantee the spiral form in the insertion and
      wrapping processes. Two CNRs can also be encapsulated in the SWCNT to form a
      helix at the same time. Furthermore, we also studied the encapsulation process of
      CNRs modified with -OH and -H functional groups. 

PMID- 24463735
TI  - Metabolic profiles of prokaryotic and eukaryotic communities in deep-sea sponge
      Neamphius huxleyi [corrected]. indicated by metagenomics.
AB  - The whole metabolism of a sponge holobiont and the respective contributions of
      prokaryotic and eukaryotic symbionts and their associations with the sponge host
      remain largely unclear. Meanwhile, compared with shallow water sponges, deep-sea
      sponges are rarely understood. Here we report the metagenomic exploration of deep
      sea sponge Neamphius huxleyi [corrected] . at the whole community level.
      Metagenomic data showed phylogenetically diverse prokaryotes and eukaryotes in
      Neamphius huxleyi [corrected]. MEGAN and gene enrichment analyses indicated
      different metabolic potentials of prokaryotic symbionts from eukaryotic
      symbionts, especially in nitrogen and carbon metabolisms, and their molecular
      interactions with the sponge host. These results supported the hypothesis that
      prokaryotic and eukaryotic symbionts have different ecological roles and
      relationships with sponge host. Moreover, vigorous denitrification, and CO2
      fixation by chemoautotrophic prokaryotes were suggested for this deep-sea sponge.
      The study provided novel insights into the respective potentials of prokaryotic
      and eukaryotic symbionts and their associations with deep-sea sponge Neamphius
      huxleyi [corrected].

PMID- 24463739
TI  - Controlled thermal sintering of a metal-metal oxide-carbon ternary composite with
      a multi-scale hollow nanostructure for use as an anode material in Li-ion
      batteries.
AB  - We report a synthetic scheme for preparing a SnO2-Sn-carbon triad inverse opal
      porous material using the controlled sintering of Sn precursor-infiltrated
      polystyrene (PS) nanobead films. Because the uniform PS nanobead film, which can
      be converted into carbon via a sintering step, uptakes the precursor solution,
      the carbon can be uniformly distributed throughout the Sn-based anode material.
      Moreover, the partial carbonization of the PS nanobeads under a controlled
      Ar/oxygen environment not only produces a composite material with an inverse opal
      like porous nanostructure but also converts the Sn precursor/PS into a SnO2-Sn-C
      triad electrode. 

PMID- 24463738
TI  - Effect of laser irradiation on the fluoride uptake of silver diamine fluoride
      treated dentine.
AB  - This study aimed to evaluate the fluoride uptake of dentine treated with a 38 %
      silver diamine fluoride (SDF) solution and laser irradiation at sub-ablative
      energy levels. Fifteen human dentine slices were prepared and divided into four
      samples each. Four types of laser were chosen: CO2 (10,600 nm), Er:YAG (2,940
      nm), Nd:YAG (1,064 nm) and Diode (810 nm). First, the four samples from 12 of the
      dentine slices were treated with SDF, and then irradiated by one of the four
      types of laser at three different settings. One sample was untreated and acted as
      a control. The setting that rendered the highest fluoride uptake was selected.
      Second, the remaining dentine slices were treated with SDF and irradiated by the
      four lasers with the selected settings. Fluoride uptake was assessed using Energy
      Dispersive X-ray Spectrometry at the dentine surface and up to 20 MUm below the
      surface. The selected settings were CO2 irradiation at 1.0 W for 1 s, Er:YAG
      irradiation at 0.5 W for 20 s, Nd:YAG irradiation at 2.0 W for 1 s and diode
      irradiation at 3.0 W for 3 s. The fluoride content (weight %) at the dentine
      surface following CO2, Er:YAG, Nd:YAG and diode irradiation was 6.91 +/- 3.15,
      4.09 +/- 1.19, 3.35 +/- 2.29 and 1.73 +/- 1.04, respectively. CO2 and Er:YAG
      irradiation resulted in higher fluoride uptake than Nd:YAG and diode irradiation
      at all levels (p < 0.05). CO2 laser and Er:YAG laser irradiation rendered higher
      fluoride uptake in the SDF-treated dentine than Nd:YAG laser and diode laser
      irradiation.

PMID- 24463740
TI  - Hydrogen-bond networks between the C-terminus and Arg from the first alpha-helix
      stabilize photoprotein molecules.
AB  - Previous studies have stated that aequorin loses most of its bioluminescence
      activity upon modification of the C-terminus, thus limiting the production of
      photoprotein fusion proteins at its N-terminus. In the present work, we
      investigate the importance of the C-terminal proline and the hydrogen bonds it
      forms for photoprotein active complex formation, stability and functional
      activity. According to the crystal structures of obelin and aequorin, two Ca(2+)
      regulated photoproteins, the carboxyl group of the C-terminal Pro forms two
      hydrogen bonds with the side chain of Arg21 (Arg15 in aequorin case) situated in
      the first alpha-helix. Whereas, deletion or substitution of the C-terminal
      proline could noticeably change the bioluminescence activity, stability or the
      yield of an active photoprotein complex. Therefore, modifications of the first
      alpha-helix Arg has a clear destructive effect on the main photoprotein
      properties. A C-terminal hydrogen-bond network is proposed to be important for
      the stability of photoprotein molecules towards external disturbances, when
      taking part in the formation of locked protein conformations and isolation of
      coelenterazine-binding cavities. 

PMID- 24463741
TI  - Dynamic expression of the suppressor of cytokine signaling-3 and cytokines in the
      cerebral basilar artery of rats with subarachnoid hemorrhage, and the effect of
      acetylcholine.
AB  - BACKGROUND: There are complex interactions between acetylcholine (ACh), the
      suppressor of cytokine signaling-3 (SOCS-3), and cytokines, however, little is
      known about their dynamic expression or their effects on cerebral vasospasm (CVS)
      after subarachnoid hemorrhage (SAH). Therefore, we aimed to describe and clarify
      the dynamic expression of SOCS-3 and cytokines after SAH, as well as the
      relationships between the levels of SOCS-3, cytokines, and ACh. METHODS: The rat
      model of single cisterna magna injection was used to mimic acute SAH. The degree
      of CVS was indicated by lumen diameter and artery wall thickness under H&E
      staining. A semi-quantitative immunohistochemical analysis method was used to
      clarify the role of SOCS-3 in the CVS after SAH. We also measured the content of
      IL-6 and IL-10 in cerebrospinal fluid. RESULTS: We found that SOCS-3 expression
      levels increased rapidly within 12 h after SAH, more slowly after 12 h, and did
      not reach a peak within 48 h. Interleukin 6 (IL-6) levels rapidly increased
      within 24 h after SAH, reached a peak 24 h after SAH, and decreased slightly at
      48 h. IL-10 levels increased during the first 6 h after SAH, after which this
      increase tapered off. ACh treatment reduced IL-6 levels and resulted in elevated
      levels of SOCS-3, but had no effect on IL-10 expression. Furthermore, ACh
      treatment relieved basilar arterial vasospasm, whereas mecamylamine pretreatment
      counteracted the activity of ACh. CONCLUSIONS: Taken together, these data
      indicate that SOCS-3 was involved in vasospasm via an IL-6- and IL-10-related
      mechanism, and that CVS following SAH could be reversed by the intraventricular
      injection of ACh.

PMID- 24463742
TI  - Is the intra-operative application of indocyanine green effective in retro
      orbital surgery?

PMID- 24463743
TI  - Synthesis, characterization and evaluation of the antioxidant potential of
      vanadium encapsulated guar gum nanoparticles.
AB  - The present study investigated the antioxidant potential of guar gum
      macroparticles (GGMs), vanadium oxide sulphate (VS) encapsulated guar gum
      macroparticles (GVMs), guar gum nanoparticles (GGNs), VS encapsulated guar gum
      nanoparticles (GVNs) and VS. GGNs and GVNs prepared by nanoprecipitation were
      characterized by SEM (scanning electron microscopy), TEM (transmission electron
      microscopy) and particle size analysis to confirm the nanostructure of the
      particles. Particle size analysis revealed that GVNs possess a size of 239 nm,
      about 148 nm larger than that of GGNs. TEM imaging and EDAX data also confirmed
      the formation of fine spherical nanoparticles with vanadium incorporation. In
      addition the larger size of GVNs also confirmed the vanadium incorporation. MTT
      assay showed that concentrations up to 100 nM of GVNs for 24 h exposure did not
      induce significant toxicity when VS was toxic (16%) at 100 nM. Various in vitro
      antioxidant assays (total reducing power, total antioxidant capacity, DPPH (2,2
      diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulphonic acid), hydroxyl radical and superoxide anion radical scavenging assays)
      revealed significantly high antioxidant potential of GVNs compared to GGNs, VS,
      GGMs and GVMs. The IC50 of GVNs was 23.21 +/- 2.1 MUg mL(-1), 33.0 +/- 2.93 MUg
      mL(-1), 21 +/- 1.98 MUg mL(-1) and 22.79 +/- 2.12 MUg mL(-1) for DPPH, ABTS,
      hydroxyl, superoxide anion scavenging activity assays respectively. The cell line
      based assay also proved that the GVN was more effective in reactive oxygen
      species (ROS) scavenging than VS against tertiary butyl hydrogen peroxide (TBHP)
      induced oxidative stress in H9c2 cell lines. The overall results indicated that
      vanadium in combination with nano guar gum exhibits significantly high
      antioxidant potential. 

PMID- 24463744
TI  - Evaluating the quality of online information about concussions.
AB  - OBJECTIVES: Compare and assess information available on the Internet about the
      definition, symptoms, treatment, and return to play recommendations after a
      concussion. METHODS: The top 10 websites generated by a Google search on the
      keyword "concussion" were evaluated by two independent researchers and three
      medical professionals for definition, signs, symptoms, home treatment, care
      seeking advice, and return to play recommendations. The medical professionals
      also rated their willingness to recommend each website to patients. RESULTS: Each
      website contained a general list of signs, symptoms, and home treatment. One
      website advised the use of ibuprofen, four advised against ibuprofen, and five
      made no medication recommendations. Nine websites contained guidance on seeking
      physician care, and eight recommended athletes not return to play until cleared
      by a healthcare professional. CONCLUSION: Nine of the websites contained
      information for each section evaluated; however, information was inconsistent.
      Healthcare providers should be aware of the variable quality of information
      available on the Internet and guide patients to more optimal resources.

PMID- 24463745
TI  - A view from the gurney.

PMID- 24463747
TI  - Xp11.2 translocation tumor: a rare cause of gross hematuria.
AB  - Xp11.2 translocation tumor is a rare but aggressive form of renal cell carcinoma
      that predominantly occurs in children but also may be found in young adults.
      Because this type of cancer is diagnosed via histologic and chromosomal analysis,
      clinicians should consider translocation tumor in the differential diagnosis of
      patients with renal lesions and gross hematuria. 

PMID- 24463748
TI  - Infraspinatus muscle atrophy from suprascapular nerve compression.
AB  - Muscle weakness without pain may signal a nerve compression injury. Because these
      injuries should be identified and treated early to prevent permanent muscle
      weakness and atrophy, providers should consider suprascapular nerve compression
      in patients with shoulder muscle weakness. 

PMID- 24463749
TI  - Evaluation and management of patients with nocturia.
AB  - Nocturia, or awakening one or more times to void at night, becomes clinically
      significant with two or more voids a night. In the past, nocturia has typically
      been viewed as a symptom of benign prostatic hyperplasia and/or overactive
      bladder syndrome. However, newer evidence supports that this is no longer just a
      symptom but a medical condition that warrants further workup and treatment given
      its effect on quality of life. The negative effects of nocturia include sleep
      fragmentation, decreased productivity at work, and increased risk of falls and
      fractures. A workup to find the underlying cause of nocturia will help guide
      treatment, which may include pharmacologic agents. 

PMID- 24463750
TI  - Pediatric wrist injury after a fall.

PMID- 24463751
TI  - Chronic myeloid leukemia and chronic lymphocytic leukemia.

PMID- 24463752
TI  - Physician assistant profile tool provides comprehensive new source of PA
      workforce data.

PMID- 24463753
TI  - Colorectal cancer screening: how old is too old?

PMID- 24463754
TI  - Sudden vision loss in a child.

PMID- 24463756
TI  - Conversation at eventide.

PMID- 24463757
TI  - Adequate management of venous thromboembolism.

PMID- 24463758
TI  - Circumstances and outcomes of out-of-hospital cardiac arrest in elementary and
      middle school students in the era of public-access defibrillation.
AB  - BACKGROUND:  Circumstances and outcomes of out-of-hospital cardiac arrest (OHCA)
      in elementary and middle school students while at school in the era of public
      access defibrillation are unknown. METHODS AND RESULTS:  We conducted a
      nationwide hospital-based survey of elementary and middle school students who had
      had OHCA of cardiac origin and received prehospital resuscitation in 2005-2009.
      Among 58 cases recruited, 90% were witnessed by bystanders; 86% had ventricular
      fibrillation as the initial rhythm; 74% were resuscitated by bystanders; 24% were
      defibrillated by bystanders; 55% occurred at school; 66% were exercise-related;
      48% were followed up before the event; 67% had structural heart disease. In
      total, 53% of overall patients and 79% of those initially defibrillated by
      bystanders had a favorable neurological outcome. Patients were more likely to be
      defibrillated by bystanders (38% vs. 8%, P=0.012) and had a more favorable
      neurological outcome in schools (69% vs. 35%, P=0.017) than in other locations.
      The majority of arrests in schools were exercise-related (84% vs. 42%, P=0.001),
      occurred at sports venues, and students were resuscitated by teachers; half of
      the cases at school occurred in patients with a pre-event follow-up. CONCLUSIONS:
      After OHCA, children were more likely to be defibrillated by bystanders and had
      a better outcome in schools than in other locations, which may be relevant to the
      circumstances of events. 

PMID- 24463759
TI  - Temperature effect on acetate and propionate consumption by sulfate-reducing
      bacteria in saline wastewater.
AB  - Seawater toilet flushing, seawater intrusion in the sewerage, and discharge of
      sulfate-rich industrial effluents elevates sulfate content in wastewater. The
      application of sulfate-reducing bacteria (SRB) in wastewater treatment is very
      beneficial; as for example, it improves the pathogen removal and reduces the
      volume of waste sludge, energy requirement and costs. This paper evaluates the
      potential to apply biological sulfate reduction using acetate and propionate to
      saline sewage treatment in moderate climates. Long-term biological sulfate
      reduction experiments at 10 and 20  degrees C were conducted in a sequencing
      batch reactor with synthetic saline domestic wastewater. Subsequently, acetate
      and propionate (soluble organic carbon) conversion rate were determined in both
      reactors, in the presence of either or both fatty acids. Both acetate and
      propionate consumption rates by SRB were 1.9 times lower at 10  degrees C than at
      20  degrees C. At 10  degrees C, propionate was incompletely oxidized to acetate.
      At 10  degrees C, complete removal of soluble organic carbon requires a
      significantly increased hydraulic retention time as compared to 20  degrees C.
      The results of the study showed that biological sulfate reduction can be a
      feasible and promising process for saline wastewater treatment in moderate
      climate. 

PMID- 24463760
TI  - Effective mutations in a high redox potential laccase from Pleurotus ostreatus.
AB  - Since the first report on a laccase, there has been a notable development in the
      interest towards this class of enzymes, highlighted from the number of scientific
      papers and patents about them. At the same time, interest in exploiting laccases
      mainly high redox potential-for various functions has been growing exponentially
      over the last 10 years. Despite decades of work, the molecular determinants of
      the redox potential are far to be fully understood. For this reason, interest in
      tuning laccase redox potential to provide more efficient catalysts has been
      growing since the last years. The work herein described takes advantage of the
      filamentous fungus Aspergillus niger as host for the heterologous production of
      the high redox potential laccase POXA1b from Pleurotus ostreatus and of one of
      its in vitro selected variants (1H6C). The system herein developed allowed to
      obtain a production level of 35,000 U/L (583.3 MUkat/L) for POXA1b and 60,000 U/L
      (1,000 MUkat/L) for 1H6C, corresponding to 13 and 20 mg/L for POXA1b and 1H6C,
      respectively. The characterised proteins exhibit very similar characteristics,
      with some exceptions regarding catalytic behaviour, stability and spectro
      electrochemical properties. Remarkably, the 1H6C variant shows a higher redox
      potential with respect to POXA1b. Furthermore, the spectro-electrochemical
      results obtained for 1H6C make it tempting to claim that we spectro
      electrochemically determined the redox potential of the 1H6C T2 site, which has
      not been studied in any detail by spectro-electrochemistry yet. 

PMID- 24463761
TI  - IS2-mediated overexpression of kfoC in E. coli K4 increases chondroitin-like
      capsular polysaccharide production.
AB  - Transposons are developing molecular tools commonly used for several
      applications: one of these is the delivery of genes into microorganisms. These
      mobile genetic elements are characterised by two repeated insertion sequences
      that flank a sequence encoding one or more orfs for a specific transposase that
      moves these sequences to other DNA sites. In the present paper, the IS2
      transposon of Escherichia coli K4 was modified in vitro by replacing the sequence
      coding for the transposase with that of the kfoC gene that codes for chondroitin
      polymerase. KfoC is responsible for the polymerisation of the bacterial capsular
      polysaccharide whose structure is analogous to that of chondroitin sulphate, a
      glycosaminoglycan with established and emerging biomedical applications. The
      recombinant construct was stably integrated into the genome of E. coli K4 by
      exploiting the transposase from endogenous copies of IS2 in the E. coli
      chromosome. A significant improvement of the polysaccharide production was
      observed, resulting in 80 % higher titres in 2.5-L fed-batch cultivations and up
      to 3.5 g/L in 22-L fed-batch cultures. 

PMID- 24463762
TI  - Cloning, expression, and biochemical characterization of a novel GH16 beta
      agarase AgaG1 from Alteromonas sp. GNUM-1.
AB  - Alteromonas sp. GNUM-1 is known to degrade agar, the main cell wall component of
      red macroalgae, for their growth. A putative agarase gene (agaG1) was identified
      from the mini-library of GNUM-1, when extracellular agarase activity was detected
      in a bacterial transformant. The nucleotide sequence revealed that AgaG1 had
      significant homology to GH16 agarases. agaG1 encodes a primary translation
      product (34.7 kDa) of 301 amino acids, including a 19-amino-acid signal peptide.
      For intracellular expression, a gene fragment encoding only the mature form (282
      amino acids) was cloned into pGEX-5X-1 in Escherichia coli, where AgaG1 was
      expressed as a fusion protein with GST attached to its N-terminal (GST-AgaG1).
      GST-AgaG1 purified on a glutathione sepharose column had an apparent molecular
      weight of 59 kDa on SDS-PAGE, and this weight matched with the estimated
      molecular weight (58.7 kDa). The agarase activity of the purified protein was
      confirmed by the zymogram assay. GST-AgaG1 could hydrolyze the artificial
      chromogenic substrate, p-nitrophenyl-beta-D-galactopyranoside but not p
      nitrophenyl-alpha-D-galactopyranoside. The optimum pH and temperature for GST
      AgaG1 activity were identified as 7.0 and 40  degrees C, respectively. GST-AgaG1
      was stable up to 40  degrees C (100 %), and it retained more than 70 % of its
      initial activity at 45  degrees C after heat treatment for 30 min. The K m and V
      max for agarose were 3.74 mg/ml and 23.8 U/mg, respectively. GST-AgaG1 did not
      require metal ions for its activity. Thin layer chromatography analysis, mass
      spectrometry, and (13)C-nuclear magnetic resonance spectrometry of the GST-AgaG1
      hydrolysis products revealed that GST-AgaG1 is an endo-type beta-agarase that
      hydrolyzes agarose and neoagarotetraose into neoagarobiose.

PMID- 24463763
TI  - Evidence for cycloisomaltooligosaccharide production from starch by Bacillus
      circulans T-3040.
AB  - Bacillus circulans T-3040 produces cycloisomaltooligosaccharide
      glucanotransferase (CITase) and cycloisomaltooligosaccharides (cyclodextrans,
      CIs) when it is grown in media containing dextran as the carbon source. To
      investigate the effects of carbon sources on CITase activity, B. circulans T-3040
      was cultured with glucose; sucrose; a mixture of isomaltose, isomaltotriose, and
      panose (IMOs); a mixture of maltohexaose and maltoheptaose (G67); dextrin
      (average degree of polymerization = 36); dextran 40; and soluble starch. In
      addition to dextran 40, CIs were produced when the T-3040 strain was grown in
      media containing soluble starch as the sole carbon source. CITase production was
      induced by dextran 40, IMOs, and soluble starch but not by G67 or dextrin, which
      suggests that alpha-1,6 glucosidic linkages are required for CITase induction.
      Although CITase was induced by IMOs, no CIs were produced in the culture. CI
      producing activity in the presence of soluble starch as the substrate (SS-CITase
      activity) was observed only in cultures containing dextran 40 or soluble starch.
      The production of CITase was significantly unaffected by glucose addition, but SS
      CITase activity almost completely disappeared after glucose addition. A 135-kDa
      protein was found to contribute to CI formation from starch in the presence of
      CITase. This protein had a disproportionation activity with
      maltooligosaccharides, and its induction and inhibition system may be different
      from those of CITase. 

PMID- 24463764
TI  - Alternative FeS cluster ligands: tuning redox potentials and chemistry.
AB  - A subset of biological Fe-S clusters contain protein-based ligands other than
      cysteine (Cys). The most common alternative ligand is histidine, while aspartate,
      arginine, and threonine ligation have also been identified. With the exception of
      the 2-Cys, 2-His ligated Rieske clusters, the functions of these uniquely ligated
      clusters are, in general, poorly understood. Recent functional studies of a set
      of 3-Cys, 1-His ligated [2Fe-2S] clusters have begun to highlight the importance
      of non-Cys ligation in controlling both the redox and chemical properties of
      these clusters as well as their physiological stability. Here, a survey of non
      Cys ligation motifs is examined along with the possible biological roles of these
      clusters. 

PMID- 24463766
TI  - High ambient temperatures and work-related injuries.

PMID- 24463765
TI  - Recent developments in copper and zinc homeostasis in bacterial pathogens.
AB  - Copper and zinc homeostasis systems in pathogenic bacteria are required to resist
      host efforts to manipulate the availability and toxicity of these metal ions.
      Central to this microbial adaptive response is the involvement of metal
      trafficking and metal-sensing proteins that ultimately exercise control of metal
      speciation in the cell. Cu-specific and Zn-specific metalloregulatory proteins
      regulate the transcription of metal-responsive genes while metallochaperones and
      related proteins ensure that these metals are appropriately buffered by the
      intracellular milieu and delivered to correct intracellular targets. In this
      review, we summarize recent findings on how bacterial pathogens mount a metal
      specific response to derail host efforts to win the 'fight over metals.' 

PMID- 24463767
TI  - Electrophysiological modulations of exogenous attention by intervening events.
AB  - The present study used event related potentials (ERPs) in a spatial cueing
      procedure to investigate the stages of processing influenced by intervening
      events presented between cues and targets, when they produce maximal behavioural
      modulations (i.e., facilitation in the absence of the intervening event, and
      inhibition of return - IOR, when the intervening event is presented). Our data
      challenge the traditional orienting-reorienting hypothesis, leading to
      alternative explanations of cueing effects that are beyond the orienting of
      attention. Peripheral cues always produced a detection cost (reflected in a
      reduced amplitude of the P100 component for cued as compared to uncued trials),
      independently on the behavioural effect that was measured. In contrast,
      facilitation was associated to modulations of later-stage components, such as
      N100, Nd, and P300. The N2pc component, usually associated to spatial selection,
      was the only component reflecting opposite and significant modulations associated
      to the behavioural effect. The present results suggest that facilitation and IOR
      can arise from changes at different stages of processing. We propose that the
      perceptual detection cost (reflected on the P100), and the hindered spatial
      selection (reflected on the N2pc) at the cued location determine the IOR effect
      at least in discrimination tasks, while the contribution of the later-stage
      components, beside attentional processes, determines other facilitatory effects
      of cueing, which altogether determine the behavioural effect that is measured. 

PMID- 24463768
TI  - Vision-related quality of life in patients with infectious keratitis.
AB  - PURPOSE: To determine the vision-related quality of life (VR-QOL) in patients
      with infectious keratitis using the 25-item National Eye Institute Visual
      Function Questionnaire (NEI VFQ-25). METHODS: Sixty-five patients with infectious
      keratitis (IK) were enrolled in the study. The NEI VFQ-25 scores and clinical and
      demographic data, including age, gender, pathogen, best corrected visual acuity
      (BCVA), and duration of the disease, were collected from the subjects. The
      subscale and composite scores were calculated and analyzed. Correlations between
      the VFQ-25 scores and the clinical and demographic features were also explored.
      RESULTS: The mean age of enrolled subjects was 48.4 years (SD, 16.2), with 44
      males (67.7%). The microbial pathogens were viruses (n = 48, 73.8%), fungi (n =
      13, 20.0%), and bacteria (n = 4, 6.2%). The mean scores of each VFQ-25 subscale
      ranged from 31.9 (SD, 28.6) for role difficulties to 92.7 (SD, 13.1) for color
      vision; the mean composite score was 58.1 (SD, 19.2). Significant differences in
      scores were observed only in the subscale of dependency among educational levels
      and in the mental health subscale and the composite among the three pathogen
      groups. Multivariate regression analysis revealed that VFQ-25 composite score
      correlated significantly with the BCVA of the worse-seeing eye, duration of the
      disease, history of operation (for IK treatment), and gender. CONCLUSIONS:
      Infectious keratitis has extensive impacts on patients and VR-QOL. The BCVA of
      worse-seeing eye, duration, history of operation for IK treatment, and gender
      contributed independently to VR-QOL. Early treatment should be encouraged to
      obtain better visual prognosis and VR-QOL for patients with IK.

PMID- 24463770
TI  - Causes and prognostic value of pre-transplant elevated kynurenine level in kidney
      allograft recipients.
AB  - BACKGROUND: The activation of the tryptophane catabolizing enzyme Indoleamine 2,3
      dioxygenase leads to the formation of kynurenine and other metabolites that
      counter-regulate immune activation resulting in restoration of immune
      homeostasis. But in chronic immune activation, as in hemodialysed patients, the
      immunosuppressive feedback mechanisms continue as indicated by elevated
      kynurenine concentrations. However, its relevance is still a matter of debate.
      MATERIAL/METHODS: This retrospective analysis presents the pre-transplant
      kynurenine levels (quantified photometrically) of 307 kidney graft recipients in
      connection with some pre- and post-transplant variables and the type of
      immunosuppression (cyclosporine-based triple drug therapy without/with ATG
      Fresenius-induction). Statistical analyses performed were analysis of variance,
      Scheffe's test for pairwise comparisons, Cox regression, Spearman's rank
      correlation, and extended segmentation analysis. RESULTS: The pre-transplant
      kynurenine level was significantly elevated as compared to healthy adults (14.1+/
      5.9 vs. 2.7+/-0.6 nmol/ml, p<0.0001), significantly higher in PRA positive than
      in PRA negative patients (16.1 vs. 12.9 nmol/ml, p<0.001) and, supporting this
      observation, also higher (p<0.0001) in a cohort with predominant (89.7%) pre
      sensitized patients (16.4+/-6.4 nmol/ml) having the longest time on the waiting
      list (median 39 months) as compared to cohorts with fewer (16.8-22%) pre
      sensitized patients (12.7+/-4.4 resp. 13.4+/-5.8 nmol/ml) having shorter times on
      the waiting list (16-24 months). Patients with immediately functioning grafts
      showed a lower pre-transplant kynurenine level than patients with non-immediately
      functioning grafts (13.5+/-6.0 vs. 14.9+/-5.7 nmol/ml, p=0.053). No associations
      were found with basic diseases, rejections, or graft survival. CONCLUSIONS: The
      pre-transplant elevated serum kynurenine levels were highly associated with the
      patient's pre-sensitization status and their longer time on hemodialysis
      treatments, but did not allow prognostic assessments.

PMID- 24463771
TI  - Drinking cold water increases blood pressure in healthy young students.

PMID- 24463772
TI  - Auxin transport and activity regulate stomatal patterning and development.
AB  - Stomata are two-celled valves that control epidermal pores whose spacing
      optimizes shoot-atmosphere gas exchange. They develop from protodermal cells
      after unequal divisions followed by an equal division and differentiation. The
      concentration of the hormone auxin, a master plant developmental regulator, is
      tightly controlled in time and space, but its role, if any, in stomatal formation
      is obscure. Here dynamic changes of auxin activity during stomatal development
      are monitored using auxin input (DII-VENUS) and output (DR5:VENUS) markers by
      time-lapse imaging. A decrease in auxin levels in the smaller daughter cell after
      unequal division presages the acquisition of a guard mother cell fate whose equal
      division produces the two guard cells. Thus, stomatal patterning requires auxin
      pathway control of stem cell compartment size, as well as auxin depletion that
      triggers a developmental switch from unequal to equal division. 

PMID- 24463773
TI  - Diagnostic testing for Giardia infections.
AB  - The traditional method for diagnosing Giardia infections involves microscopic
      examination of faecal specimens for Giardia cysts. This method is subjective and
      relies on observer experience. From the 1980s onwards, objective techniques have
      been developed for diagnosing Giardia infections, and are superseding diagnostic
      techniques reliant on microscopy. Detection of Giardia antigen(s) by immunoassay
      is the basis of commercially available diagnostic kits. Various nucleic acid
      amplification techniques (NAATs) can demonstrate DNA of Giardia intestinalis, and
      have the potential to become standard approaches for diagnosing Giardia
      infections. Of such techniques, methods involving either fluorescent microspheres
      (Luminex) or isothermal amplification of DNA (loop-mediated isothermal
      amplification; LAMP) are especially promising. 

PMID- 24463769
TI  - Stereoacuity of preschool children with and without vision disorders.
AB  - PURPOSE: To evaluate associations between stereoacuity and presence, type, and
      severity of vision disorders in Head Start preschool children and determine
      testability and levels of stereoacuity by age in children without vision
      disorders. METHODS: Stereoacuity of children aged 3 to 5 years (n = 2898)
      participating in the Vision in Preschoolers (VIP) Study was evaluated using the
      Stereo Smile II test during a comprehensive vision examination. This test uses a
      two-alternative forced-choice paradigm with four stereoacuity levels (480 to 60
      seconds of arc). Children were classified by the presence (n = 871) or absence (n
      = 2027) of VIP Study-targeted vision disorders (amblyopia, strabismus,
      significant refractive error, or unexplained reduced visual acuity), including
      type and severity. Median stereoacuity between groups and among severity levels
      of vision disorders was compared using Wilcoxon rank sum and Kruskal-Wallis
      tests. Testability and stereoacuity levels were determined for children without
      VIP Study-targeted disorders overall and by age. RESULTS: Children with VIP Study
      targeted vision disorders had significantly worse median stereoacuity than that
      of children without vision disorders (120 vs. 60 seconds of arc, p < 0.001).
      Children with the most severe vision disorders had worse stereoacuity than that
      of children with milder disorders (median 480 vs. 120 seconds of arc, p < 0.001).
      Among children without vision disorders, testability was 99.6% overall,
      increasing with age to 100% for 5-year-olds (p = 0.002). Most of the children
      without vision disorders (88%) had stereoacuity at the two best disparities (60
      or 120 seconds of arc); the percentage increasing with age (82% for 3-, 89% for 4
      , and 92% for 5-year-olds; p < 0.001). CONCLUSIONS: The presence of any VIP Study
      targeted vision disorder was associated with significantly worse stereoacuity in
      preschool children. Severe vision disorders were more likely associated with
      poorer stereopsis than milder or no vision disorders. Testability was excellent
      at all ages. These results support the validity of the Stereo Smile II for
      assessing random-dot stereoacuity in preschool children.

PMID- 24463775
TI  - Manganese carbonyl terpyridyl complexes: their synthesis, characterization and
      potential application as CO-release molecules.
AB  - Mn(I) carbonyl terpyridyl complexes have been synthesized and characterized. The
      tricarbonyl derivative exhibits interesting behaviors for controlled CO-release
      by both thermal and photosynthetic pathways. 

PMID- 24463774
TI  - Molecular and biochemical identification of inositol 1,3,4,5,6-pentakisphosphate
      2-kinase encoding mRNA variants in castor bean (Ricinus communis L.) seeds.
AB  - During seed development, phytic acid (PA) associated with mineral cations is
      stored as phytin and mobilized following germination in support of seedling
      growth. Two parallel biosynthetic pathways for PA have been proposed; yet the
      pathway is still poorly understood in terms of its regulation and the enzymes
      involved. Here, the castor bean (Ricinus communis L.) gene for inositol 1,3,4,5,6
      pentakisphosphate 2-kinase (RcIPK1) has been identified. This encodes the enzyme
      implicated in catalyzing the final reaction in PA biosynthesis, and its
      expression is enhanced in isolated germinated embryos by application of phosphate
      and myo-inositol (Ins). Even though only one copy of the RcIPK1 gene is present
      in the genome, numerous RNA variants are present, most likely due to alternative
      splicing. These are translated into six closely related protein isoforms
      according to in silico analysis. Functional analyses using yeast ipk1Delta
      revealed that only three of the mRNA variants can rescue a temperature-sensitive
      growth phenotype of this strain. High-performance liquid chromatography (HPLC)
      analysis of the synthesized inositol phosphates demonstrated that the ability to
      complement the missing yeast IPK1 enzyme is associated with the production of
      enzyme activity. The three active isoforms possess unique conserved motifs
      important for IPK1 catalytic activity. 

PMID- 24463776
TI  - Recent advances in research on human aortic valve calcification.
AB  - Aortic valve calcification can aggravate aortic stenoses, and it is a significant
      cause of sudden cardiac death. The increasing number of patients with age-related
      calcification is a problem in developed nations. However, the only treatment
      option currently available is highly invasive cardiac valve replacement.
      Therefore, clarification of the etiology of calcification is urgently needed to
      develop drug therapies and prevention methods. Recent studies have revealed that
      calcification is not a simple sedimentation of a mineral through a
      physicochemical phenomenon; various factors dynamically contribute to the
      mechanism. Further, we are finally beginning to understand the cellular origins
      of calcification, which had been unclear for a long time. Based on these findings
      that help to clarify potential drug targets, we expect to establish drug
      therapies that reduce the stress on patients. In this paper, I introduce the
      latest findings on cells that are most likely to contribute to calcification and
      on calcification-related factors that may lead to the development of drug
      therapies. 

PMID- 24463777
TI  - Regeneration of injured renal tubules.
AB  - Acute kidney injury (AKI), clinically defined by high serum creatinine and low
      urine flow, has many complicated pathophysiological features including tubular
      and glomerular injury. Although renal tubules are thought to be constituted by
      highly differentiated epithelial cells, it is possible to repair injured nephrons
      by the healing process. Several studies have revealed that AKI, especially AKI
      caused by ischemia/reperfusion injury or nephrotoxic medication, depends on a
      number of factors, including activation of transcriptional factors, endothelial
      injury of peritubular small vessels, immune responses, and inflammatory processes
      associated with necrosis and apoptosis of renal tubular epithelium. For
      regeneration of injured tubules, partly dedifferentiated progenitor-like cells
      fill the injured site and constitute the tubular structure and function, although
      the source of these cells is still under debate. It is essential to understand
      the molecular, cellular, and genetic mechanisms of AKI and tubular regeneration
      for the development of therapies to prevent and treat kidney injury. 

PMID- 24463778
TI  - N-stearoyltyrosine protects against glutamate-induced oxidative toxicity by an
      apoptosis-inducing factor (AIF)-mediated caspase-independent cell death pathway.
AB  - N-stearoyltyrosine (NsTyr), a synthesized anandamide (AEA) analogue, could exert
      potent neuroprotective effects on cerebral ischemia models both in vivo and in
      vitro via intervening in multiple injuries. Glutamate, a major excitatory
      neurotransmitter, plays a critical role during stroke/cerebral ischemia. In this
      study, we explored the protective effects of NsTyr on glutamate neurotoxicity in
      PC12 cells and investigated its underlying mechanisms. NsTyr treatment attenuated
      glutamate-induced oxidative toxicity in a dose-dependent manner and the best
      performance was observed at 10 MUMU. NsTyr treatment suppressed glutamate-induced
      upregulation of lipoxygenase 12/15 (LOX 12/15) activity and reactive oxygen
      species (ROS) elevation, attenuated the increase of BH3-interacting domain death
      agonist (Bid) in the mitochondria, prevented the loss of mitochondria membrane
      potential and consequently inhibited apoptosis-inducing factor (AIF)
      translocation into the nucleus. The results demonstrated that NsTyr could protect
      cells against AIF-mediated caspase-independent cell death induced by glutamate,
      which may be due to the blockage of Bid-mediated mitochondrial damage via
      reducing LOX 12/15 activity and ROS accumulation.

PMID- 24463779
TI  - Evaluation of a method for the assessment of anterior acetabular coverage and hip
      joint space width.
AB  - OBJECTIVE: The false-profile view (FP) is an oblique view of the acetabulum and a
      true lateral view of femur and joint. It evaluates anterior and posterior hip
      joint space width (JSW) and anterior acetabular coverage using the vertical
      center margin angle (VCA). The biplanar slot scanner (SS) allows simultaneous
      bilateral acquisitions of oblique views of hip joints. The aim of this work was
      to compare SS versus FP for the evaluation of VCA and JSW and to test its
      reproducibility and validity. MATERIALS AND METHODS: A prospective study of 28
      patients (55 hips) with hip pain was performed from November 2011 until May 2012.
      Two readers measured VCA and JSW. JSW was normalized by the diameter of the
      femoral head for each technique. The radiation exposure was recorded and compared
      between the two modalities. Student's t test and the Pearson's correlation
      assessed the agreement between SS and FP. The intraclass correlation coefficient
      (ICC) was used to assess the interobserver agreement. RESULTS: The mean VCA angle
      was 32.1 degrees  (+/- 7.1 degrees ) and 30.3 degrees  (+/- 8.5 degrees ) with FP
      and SS, respectively. The coefficient of correlation was 0.90 (p < 0.01). The
      coefficient of correlation of normalized JSW was 0.83, 0.85, and 0.87 at
      anterior, vertical, and posterior points, respectively). The ICC was between 0.69
      and 0.81 for each modality. The mean radiation exposure was 1.33 (+/- 0.02) mGy
      versus 8.69 (+/-0.04) mGy for FP and SS, respectively (p < 0.0001). CONCLUSIONS:
      SS has the potential advantages of simultaneous bilateral acquisition, higher
      standardization, and is less irradiating. SS is reliable for coxometry.

PMID- 24463780
TI  - Visualization of joint and bone using dual-energy CT arthrography with contrast
      subtraction: in vitro feasibility study using porcine joints.
AB  - OBJECTIVE: To assess the feasibility of subtracting various concentrations of
      iodinated contrast material on dual-energy computed tomographic (DECT)
      arthrography to provide both CT arthrography and virtual unenhanced CT (VUCT) in
      a single CT acquisition. MATERIALS AND METHODS: This was an in vitro study for
      which institutional review board approval was not required. CT arthrographies of
      12 joints of pig cadavers were obtained using dual-energy CT. Various
      concentrations of iodinated contrast material, 25% (75 mg/ml), 50% (150 mg/ml),
      75% (225 mg/ml), and 100% (300 mg/ml) were used for the DECT arthrography. The
      paired regions of interest (ROI) were drawn over the same location on two paired
      CT scans at different tube voltages (80 kVp and 140 kVp). The average Hounsfield
      units (HU) ratio of the contrast media(HU on CT at 80 kVp/HU on CT at 140 kVp)
      was calculated for each joint. Subtraction of contrast material was carried out
      using VUCT application RESULTS: The 25% iodinated contrast mixture was
      successfully subtracted from DECT arthrography of four joints, in which the
      average HU ratio ranged from 1.95 to 2.0. The subtraction of the 50%,75%, and
      100% iodine contrast mixtures was not successful, because of the upper
      demonstrable HU limit in dual-energy CT. CONCLUSIONS: DECT arthrography with 25%
      iodinated contrast medium injection can provide both CT arthrography and virtual
      unenhanced images in a single CT acquisition.

PMID- 24463782
TI  - One-minute synthesis of crystalline microporous aluminophosphate (AlPO4-5) by
      combining fast heating with a seed-assisted method.
AB  - Herein, we report a rapid route for the synthesis of AlPO4-5. By combining fast
      heating in a tubular reactor with a seed-assisted method, both of which were
      found to be crucial, the preparation of AlPO4-5 was completed in one minute,
      making this route the fastest known for the preparation of the crystalline
      microporous materials. 

PMID- 24463781
TI  - Interactions between mesenchymal stem cells, adipocytes, and osteoblasts in a 3D
      tri-culture model of hyperglycemic conditions in the bone marrow
      microenvironment.
AB  - Recent studies have found that uncontrolled diabetes and consequential
      hyperglycemic conditions can lead to an increased incidence of osteoporosis.
      Osteoblasts, adipocytes, and mesenchymal stem cells (MSCs) are all components of
      the bone marrow microenvironment and thus may have an effect on diabetes-related
      osteoporosis. However, few studies have investigated the influence of these three
      cell types on each other, especially in the context of hyperglycemia. Thus, we
      developed a hydrogel-based 3D culture platform engineered to allow live-cell
      retrieval in order to investigate the interactions between MSCs, osteoblasts, and
      adipocytes in mono-, co-, and tri-culture configurations under hyperglycemic
      conditions for 7 days of culture. Gene expression, histochemical analysis of
      differentiation markers, and cell viability were measured for all cell types, and
      MSC-laden hydrogels were degraded to retrieve cells to assess their colony
      forming capacity. Multivariate models of gene expression data indicated that
      primary discrimination was dependent on the neighboring cell type, validating the
      need for co-culture configurations to study conditions modeling this disease
      state. MSC viability and clonogenicity were reduced when mono- and co-cultured
      with osteoblasts at high glucose levels. In contrast, MSCs showed no reduction of
      viability or clonogenicity when cultured with adipocytes under high glucose
      conditions, and the adipogenic gene expression indicates that cross-talk between
      MSCs and adipocytes may occur. Thus, our unique culture platform combined with
      post-culture multivariate analysis provided a novel insight into cellular
      interactions within the MSC microenvironment and highlights the necessity of
      multi-cellular culture systems for further investigation of complex pathologies
      such as diabetes and osteoporosis. 

PMID- 24463783
TI  - Determinants of viremia copy-years in people with HIV/AIDS after initiation of
      antiretroviral therapy.
AB  - BACKGROUND: Recent studies suggest higher cumulative HIV viremia exposure
      measured as viremia copy-years (VCY) is associated with increased all-cause
      mortality. The objectives of this study are (1) report the association between
      VCY and all-cause mortality and (2) assess associations between common patient
      characteristics and VCY. METHODS: Analyses were based on patients recruited to
      the Australian HIV Observational Database (AHOD) who had received >=24 weeks of
      antiretroviral therapy (ART). We established VCY after 1, 3, 5, and 10 years of
      ART by calculating the area under the plasma viral load time series. We used
      survival methods to determine the association between high VCY and all-cause
      mortality. We used multivariable mixed-effect models to determine predictors of
      VCY. We compared a baseline information model with a time-updated model to
      evaluate discrimination of patients with high VCY. RESULTS: Of the 3021 AHOD
      participants who initiated ART, 2073 (69%), 1667 (55%), 1267 (42%), and 638 (21%)
      were eligible for analysis at 1, 3, 5, and 10 years of ART, respectively.
      Multivariable-adjusted hazard ratio association between all-cause mortality and
      high VCY was statistically significant, hazard ratio 1.52 (1.09, 2.13), P = 0.01.
      Predicting high VCY after 1 year of ART for a time-updated model compared with a
      baseline information model, the area under the sensitivity/specificity curve was
      0.92 vs. 0.84; and at 10 years of ART, area under the sensitivity/specificity
      curve was 0.87 vs. 0.61, respectively. CONCLUSION: A high cumulative measure of
      viral load after initiating ART is associated with increased risk of all-cause
      mortality. Identifying patients with high VCY is improved by incorporating time
      updated information.

PMID- 24463786
TI  - Traumatic orbital encephalocele in an infant: using the fracture line to our
      advantage.

PMID- 24463784
TI  - Variants in host viral replication cycle genes are associated with heterosexual
      HIV-1 acquisition in Africans.
AB  - OBJECTIVE: We evaluated genetic variants in 51 candidate genes encoding proteins
      that interact with HIV-1 during the virus life cycle for association with HIV-1
      outcomes in an African cohort. METHODS: Using a nested case-control study within
      a cohort of heterosexual HIV-1-serodiscordant couples, we genotyped 475 haplotype
      tagging single-nucleotide polymorphisms (tagSNPs) and 18 SNPs previously
      associated with HIV-1 transmission and/or progression (candidate SNPs) in 51 host
      genes. We used logistic and Cox proportional hazard regression with adjustment
      for sex, age, and population stratification to detect SNP associations with HIV-1
      acquisition, plasma HIV-1 set point, and a composite measure of HIV-1 disease
      progression. Significant thresholds for tagSNP, but not candidate SNP,
      associations were subjected to Bonferroni correction for multiple testing.
      RESULTS: We evaluated 491 HIV-1-infected and 335 HIV-1-uninfected individuals for
      493 SNPs, 459 of which passed quality control filters. Candidate SNP PPIA
      rs8177826 and tagSNP SMARCB1 rs6003904 were significantly associated with HIV-1
      acquisition risk (odds ratio = 0.14, P = 0.03, and odds ratio = 2.11, Pcorr =
      0.01, respectively). Furthermore, the TT genotype for CCR5 rs1799988 was
      associated with a mean 0.2 log10 copies per milliliter lower plasma HIV-1 RNA set
      point (P = 0.04). We also identified significant associations with HIV-1 disease
      progression for variants in FUT2 and MBL2. CONCLUSIONS: Using a targeted gene
      approach, we identified variants in host genes whose protein products interact
      with HIV-1 during the virus replication cycle and were associated with HIV-1
      outcomes in this African cohort.

PMID- 24463785
TI  - Association mapping of seed quality traits using the Canadian flax (Linum
      usitatissimum L.) core collection.
AB  - KEY MESSAGE: The identification of stable QTL for seed quality traits by
      association mapping of a diverse panel of linseed accessions establishes the
      foundation for assisted breeding and future fine mapping in linseed. Linseed oil
      is valued for its food and non-food applications. Modifying its oil content and
      fatty acid (FA) profiles to meet market needs in a timely manner requires clear
      understanding of their quantitative trait loci (QTL) architectures, which have
      received little attention to date. Association mapping is an efficient approach
      to identify QTL in germplasm collections. In this study, we explored the
      quantitative nature of seed quality traits including oil content (OIL), palmitic
      acid, stearic acid, oleic acid, linoleic acid (LIO) linolenic acid (LIN) and
      iodine value in a flax core collection of 390 accessions assayed with 460
      microsatellite markers. The core collection was grown in a modified augmented
      design at two locations over 3 years and phenotypic data for all seven traits
      were obtained from all six environments. Significant phenotypic diversity and
      moderate to high heritability for each trait (0.73-0.99) were observed. Most of
      the candidate QTL were stable as revealed by multivariate analyses. Nine
      candidate QTL were identified, varying from one for OIL to three for LIO and LIN.
      Candidate QTL for LIO and LIN co-localized with QTL previously identified in bi
      parental populations and some mapped nearby genes known to be involved in the FA
      biosynthesis pathway. Fifty-eight percent of the QTL alleles were absent
      (private) in the Canadian cultivars suggesting that the core collection possesses
      QTL alleles potentially useful to improve seed quality traits. The candidate QTL
      identified herein will establish the foundation for future marker-assisted
      breeding in linseed.

PMID- 24463787
TI  - Impaired myocardium energetics associated with the risk for new-onset atrial
      fibrillation after isolated coronary artery bypass graft surgery.
AB  - BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is one of the most
      common complications occurring in 10-40% of patients after coronary artery bypass
      graft (CABG) surgery. Recent studies suggest that dysmetabolism may contribute to
      the pathogenesis of atrial fibrillation; however, the putative mechanism in
      patients undergoing CABG surgery is unknown. Peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC-1alpha) has been demonstrated as a master
      regulator of myocardial energy metabolism, and glucose transporter 3 (GLUT3) has
      both a higher affinity for glucose and a much greater transport capacity compared
      with GLUT1, GLUT2, and GLUT4. We sought to evaluate the role of energy
      metabolism, especially the glucose metabolism, on patients after isolated CABG
      surgery. METHODS AND RESULTS: Right atrial appendages were obtained from 79
      patients who were in normal sinus rhythm and undergoing isolated CABG; those who
      exhibited new-onset POAF (n=22) or remained in sinus rhythm (n=57) were
      prospectively matched on the basis of preoperative, intraoperative, and
      postoperative characteristics. POAF was assessed by electrocardiogram and must
      have required the initiation of antiarrhythmic therapy or anticoagulation. Local
      PGC-1alpha and GLUT3 concentrations were quantified by enzyme-linked
      immunosorbent assay in tissue homogenates. The comparison of mRNA expression was
      tested by quantitative real-time PCR. PGC-1alpha and GLUT3 levels and the related
      protein mRNA expression were significantly reduced in POAF patients compared with
      controls (P<0.05). This selective reduction in PGC-1alpha was associated with the
      presence of diabetes mellitus (P<0.05). CONCLUSION: Patients who have low PGC
      1alpha and GLUT3 levels are at increased risk for new-onset POAF. The
      myofibrillar energetic impairment may be important in the pathogenesis of atrial
      fibrillation.

PMID- 24463788
TI  - Urinary lignans and inflammatory markers in the US National Health and Nutrition
      Examination Survey (NHANES) 1999-2004 and 2005-2008.
AB  - PURPOSE: Chronic inflammation has been implicated in the etiology of various
      chronic diseases. We previously found that certain urinary isoflavones are
      associated with markers of inflammation. In the present study, we examined the
      associations of serum C-reactive protein (CRP) and white blood cell (WBC) count
      with lignans, which are more frequent in the Western diet than isoflavones.
      METHODS: Our analysis included 2,028 participants of NHANES 2005-2008 and 2,628
      participants of NHANES 1999-2004 aged 18 years and older. The exposures of
      interest were urinary mammalian lignans (enterodiol and enterolactone). Outcome
      variables were two inflammatory markers (CRP [<=10 mg/L] and WBC [>=3.0 and
      <=11.7 (1,000 cells/MUL)]). Log-transformed CRP concentration and WBC count by
      log-transformed creatinine-standardized concentrations of mammalian lignans were
      used for linear regression. RESULTS: Statistically significant inverse
      associations of urinary lignan, enterodiol, and enterolactone concentrations with
      circulating CRP and WBC counts were observed in the multivariate-adjusted models:
      In NHANES 2005-2008, per one-percent increase in lignan concentrations in the
      urine, CRP concentrations and WBC counts decreased by 8.1 % (95 % CI -11.5, -4.5)
      and 1.9 % (95 % CI -2.7; -1.2), respectively. Per one-percent increase in
      enterodiol and enterolactone, WBC counts decreased by 2.1 % (95 % CI -2.8, -1.3)
      and 1.3 % (95 % CI -1.9, -0.6), respectively. In NHANES 1999-2004, analogous
      results were 3.0 % (95 % CI -5.6, -0.3), 1.2 % (95 % CI -2.0; -0.4), 1.0 % (95 %
      CI -1.8, -0.2), and 0.8 % (95 % CI -1.4, 0.2). CONCLUSIONS: Mammalian lignans
      were inversely associated with markers of chronic inflammation. Due to the cross
      sectional design, our findings require confirmation in prospective studies.

PMID- 24463789
TI  - Evaluation of epidemiological factors in survival of patients with de novo
      myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) prognosis is currently based solely on clinical
      parameters. The identification of additional factors associated with MDS outcome
      could be used to further improve the current scoring system such as the
      International Prognostic Scoring System (IPSS). The present study evaluates the
      role of epidemiological markers as predictors of survival for 365 adult de novo
      MDS patients. Multivariable Cox regression analysis was used to estimate overall
      survival. Median follow-up time was 22 months. At the time of last follow-up, 271
      patients (74.3 %) had died. For all MDS patients, medium-high lifetime
      occupational agrochemical exposure (HR 1.85, CI 1.19-2.89) remained as an
      independent predictor of MDS survival. Stratified analysis by gender showed that
      >= 25 pack-years smoked (HR 1.44, CI 1.001-2.09) and medium-high lifetime
      occupational agrochemical exposure (HR 1.84, CI 1.15-2.97) were independent
      predictors of MDS survival in men, but not in women. For MDS patients stratified
      by IPSS categories, >= 25 pack-years smoked (HR 1.75, CI 1.005-3.06) was an
      independent predictor for intermediate 1 IPSS risk group only, and medium-high
      lifetime occupational agrochemical exposure was associated with increased
      mortality (HR 4.36, CI 1.20-15.8) in the high IPSS risk group. Smoking and
      lifetime occupational agrochemical exposure may play a role in MDS survival.
      Incorporating relevant epidemiological markers with known clinical predictors of
      outcome may help physician stratify patients and customize treatment strategies
      to improve the outcome of MDS.

PMID- 24463790
TI  - Incidence of second sarcomas: a cancer registry-based study.
AB  - BACKGROUND: In high-quality cancer registration systems, about one in eight
      incident cancers are second primary cancers. This is due to a combination of
      careful diagnostic ascertainment, shared genetic determinants, shared exposure to
      environmental factors and consequences of treatment for first cancer. METHODS: We
      used data derived from the Swiss population-based cancer Registries of Vaud and
      Neuchatel, including 885,000 inhabitants. RESULTS: Among 107,238 (52% males)
      first cancers occurring between 1976 and 2010, a total of 126 second sarcomas
      were observed through active and passive follow-up versus 68.2 expected,
      corresponding to a standardized incidence ratio (SIR) of 1.85 (95 % CI 1.5-2.2).
      Significant excess sarcoma risks were observed after skin melanoma (SIR = 3.0),
      breast cancer (2.2), corpus uteri (2.7), testicular (7.5), thyroid cancer (4.2),
      Hodgkin lymphoma (5.7) and leukemias (4.0). For breast cancer, the SIR was 3.4 >=
      5 years after sarcoma diagnosis. CONCLUSIONS: The common denominator of these
      neoplasms is the utilization of radiotherapy in their management. Some sarcomas
      following breast cancer may be due to shared genetic components (i.e., in the Li
      Fraumeni syndrome), as well as possibly to shared environmental factors, with
      sarcomas, including overweight, selected dietary and reproductive factors which
      are, however, too little defined for any quantitative risk assessment.

PMID- 24463791
TI  - Co-occurrence of carbapenem and aminoglycoside resistance genes among multidrug
      resistant clinical isolates of Acinetobacter baumannii from Cracow, Poland.
AB  - BACKGROUND: Acinetobacter baumannii is a significant hospital pathogen,
      possessing a considerable degree of antimicrobial resistance. A. baumannii
      resistance to carbapenems and aminoglycosides is mostly conferred by class D OXA
      carbapenemases and aminoglycoside-modifying enzymes, respectively. The aim of
      this study was to determine the prevalence of selected genes encoding OXA
      carbapenemases and aminoglycoside-modifying enzymes in multidrug-resistant
      strains of A. baumannii. MATERIAL AND METHODS: The study included 61 carbapenem
      resistant and aminoglycoside-nonsusceptible A. baumannii isolates, collected
      between 2009 and 2011 in Cracow, Poland. Selected resistance genes, including:
      blaOXA-51-like, blaOXA-23-like, blaOXA-40-like, blaOXA-58-like, aac(6')-Ih,
      aac(3)-Ia, aac(3)-IIa, aac(6')-Ib, aph(3')-Ia and aph(3')-VI, were detected by
      PCR method. RESULTS: The blaOXA-51-like genes were detected in all isolates,
      while acquired carbapenemase encoding genes were found in 96.7% of tested
      strains. Presence of blaOXA-40-like and blaOXA-23-like genes was observed among
      65.6% and 27.9% of isolates, respectively. Assayed aminoglycoside resistance
      genes were found to harbor 98.4% of isolates. Among tested strains, we observed
      the following percentages of resistance determinants: aac(3)-Ia - 78.7%, aph(3')
      VI - 78.7% and aph(3')-Ia - 27.9%. Analysis of co-occurrence of carbapenem and
      aminoglycoside resistance genes revealed the highest percentage of strains
      possessing blaOXA-40-like, aac(3)-Ia, and aph(3')-VI genes (44.3%). CONCLUSIONS:
      The blaOXA-40-like and aac(3)-Ia/aph(3')-VI were the most prevalent genes
      encoding acquired OXA carbapenemases and aminoglycoside-modifying enzymes,
      respectively, among A. baumannii strains in Cracow, Poland. Genes conferring
      resistance to carbapenems and aminoglycosides coexisted in the clinical strains
      of A. baumannii. The phenomenon of A. baumannii resistance indicates the
      necessity of monitoring for the presence of the resistance genes.

PMID- 24463792
TI  - Multi-ion versus single-ion conduction mechanisms can yield current rectification
      in biological ion channels.
AB  - There is clear evidence that the net magnitude of negative charge at the
      intracellular end of inwardly rectifying potassium channels helps to generate an
      asymmetry in the magnitude of the current that will pass in each direction.
      However, a complete understanding of the physical mechanism that links these
      charges to current rectification has yet to be obtained. Using Brownian dynamics,
      we compare the conduction mechanism and binding sites in rectifying and non
      rectifying channel models. We find that in our models, rectification is a
      consequence of asymmetry in the hydrophobicity and charge of the pore lining. As
      a consequence, inward conduction can occur by a multi-ion conduction mechanism.
      However, outward conduction is restricted, since there are fewer ions at the
      intracellular entrance and outwardly moving ions must cross the pore on their
      own. We pose the question as to whether the same mechanism could be at play in
      inwardly rectifying potassium channels.

PMID- 24463793
TI  - Polystyrene sulphonic acid resins with enhanced acid strength via macromolecular
      self-assembly within confined nanospace.
AB  - Tightening environmental legislation is driving the chemical industries to
      develop efficient solid acid catalysts to replace conventional mineral acids.
      Polystyrene sulphonic acid resins, as some of the most important solid acid
      catalysts, have been widely studied. However, the influence of the morphology on
      their acid strength--closely related to the catalytic activity--has seldom been
      reported. Herein, we demonstrate that the acid strength of polystyrene sulphonic
      acid resins can be adjusted through their reversible morphology transformation
      from aggregated to swelling state, mainly driven by the formation and breakage of
      hydrogen bond interactions among adjacent sulphonic acid groups within the
      confined nanospace of hollow silica nanospheres. The hybrid solid acid catalyst
      demonstrates high activity and selectivity in a series of important acid
      catalysed reactions. This may offer an efficient strategy to fabricate hybrid
      solid acid catalysts for green chemical processes.

PMID- 24463794
TI  - Photoluminescence of a single complex plasmonic nanoparticle.
AB  - We report detailed investigations of the photoluminescence (PL) generated from an
      individual gold nanoflower, a highly branched plasmonic nanoparticle. Compared to
      nanostructures with simple shapes, such as spheres, nanorods, and bipyramids,
      nanoflowers exhibit more distinct features, i.e., the PL spectra and far-field
      emission patterns are strongly dependent on the wavelength and polarization of
      the excitation light. The experimental results are qualitatively explained using
      theoretical calculations. In addition, the intrinsic PL signal is highly
      dominated by localized surface plasmon resonances. The crucial role of plasmonic
      coupling in complex nanostructures during the plasmon-enhanced PL process is
      highlighted. The findings contribute to a deeper understanding of the PL
      properties of metallic nanoparticles. This study will be beneficial for several
      potential applications, including optical imaging and sensing in the fields of
      materials science and biology. 

PMID- 24463795
TI  - Needle-stick injury among health care workers in hemodialysis units in Nigeria: a
      multi-center study.
AB  - BACKGROUND: Needle-stick and sharps injuries carry the risk of infection and are
      occupational hazards for all health care professionals involved in clinical care.
      OBJECTIVE: To determine the frequency and factors contributing to needle-stick
      injury (NSI) among health care workers of dialysis units in Lagos, Nigeria.
      METHODS: Data were obtained by anonymous, self-reporting questionnaire from staff
      of 4 hemodialysis units between October and December 2011. Information on
      demographics, job category and duration, details of NSI in the past, kind of
      activity and procedure under which the NSI occurred, if injury was reported,
      vaccination status of staff, and post-exposure treatment received were obtained.
      RESULTS: The study population included 38 (37.3%) doctors, 42 nurses (41.2%), 14
      (13.7%) dialysis technicians and 8 (7.8%) ancillary staff. There were 39 (38.2%)
      males. The mean+/-SD age of the study population was 34.4+/-8.3 years. 25 (24.5%)
      staff had suffered NSI in the last 12 months and 41 (40.2%) in their entire
      working career. The most common activity leading to NSI was recapping of needles
      (45%), improper disposal of needles (30%), and venous cannulation and setting of
      drips (27.5%). NSI was significantly (p=0.016) higher among those with work
      experience between 6 and 10 years than others. Hollow bore needles were
      responsible for 82.9% of the NSIs. Only 15 (37%) respondents reported their NSI
      to their unit head or designated officer in order to get medical advice.
      CONCLUSION: In Lagos, Nigeria, NSI is common among hemodialysis staff and is
      under-reported. Many NSIs can be prevented by adhering to the practice of
      universal precautions as well as education of staff on such precautionary
      methods.

PMID- 24463796
TI  - Use of hub cutters and the volume of sharp waste and occurrence of needle-stick
      injuries during 2011 mass immunization campaigns against yellow fever in Ghana: a
      cohort study.
AB  - BACKGROUND: Current WHO best infection control practices for injections do not
      address the use of hub cutters due to insufficient evidence on safety and
      efficacy. OBJECTIVE: To assess the impact of the use of hub cutters on 1) the
      frequency of needle-stick injuries (NSIs) and other blood exposures among workers
      and 2) the volume of sharps waste in a mass vaccination campaign setting.
      METHODS: During yellow fever vaccination in Ghana, we conducted a cohort study on
      the use of hub cutters. We compared two groups---one group using hub cutters and
      a control group---for the occurrences of NSIs and the volume of sharp waste
      produced. RESULTS: In the control arm, vaccinators used 284 482 syringes in 825
      vaccination sessions. In the group using hub cutter, vaccinators used 397 079
      syringes in 1599 sessions. Among vaccinators, the rate of NSI was not
      significantly (p=0.14) different between the hub cutter users (0.15/10 000
      syringes) and the control group (0.04/10 000). Factors such as workload, lack of
      organization and pressure seemed to have influence the occurrence of NSIs. With
      all the limitations of the work, the volume of sharp waste per 10 000 syringes
      was 0.24 m(3) in the hub cutter users and 0.41 m(3) in the control group---a
      reduction of 41.2%. Vaccinators found hub cutters easy to use and safe. Use of
      hub cutter was not associated with increased duration of work. CONCLUSION: The
      use of hub cutters did not increase the risk of NSIs. More training is needed to
      facilitate its implementation in mass campaign setting.

PMID- 24463797
TI  - The management of dental waste in dental offices and clinics in Shiraz, Southern
      Iran.
AB  - BACKGROUND: Dental waste can be hazardous to humans and the environment.
      OBJECTIVE: To determine the current status of dental waste management in private
      and public dental clinics and private dental offices in Shiraz, southern Iran.
      METHODS: This cross-sectional study was conducted at the Shiraz University of
      Medical Sciences from February through June 2013. A stratified random sampling
      method was used to study 86 private offices, 14 private clinics and 10 public
      clinics. Types of waste studied included mercury and amalgam, lead foil packets,
      sharps, infectious tissues and fluids, pharmaceuticals and domestic waste
      materials. Compliance with established standards by the monitored dental offices
      and clinics and public clinics were compared. RESULTS: 89.1% of dental offices
      and clinics disposed their infectious waste with domestic waste. Only 60% of
      centers used standard method for sharps disposal. None of the dental centers
      disposed their pharmaceutical waste and x-ray fixer waste by standard methods.
      Less than 10% of centers recycled the amalgam and lead foil pockets waste to the
      manufacture. CONCLUSION: Government agencies should establish monitoring programs
      for all dental offices and clinics to identify noncompliant activity and enforce
      recommended regulations.

PMID- 24463798
TI  - Factors influencing compliance with infection control practice in Japanese
      dentists.
AB  - BACKGROUND: In recent years, dentists have more opportunity of treating patients
      infected with blood-borne pathogens. Although compliance with infection control
      practice (ICP) in dental practice is required, it is not still sufficiently
      spread in Japan. OBJECTIVE: To identify factors associated with compliance with
      ICPs in the population of Japanese dentists. METHODS: In a questionnaire-based
      cross-sectional study in 2009, 2134 dentists in Aichi prefecture, Japan, were
      surveyed. They were asked for their demographic characteristics, willingness to
      treat HIV/AIDS patients, and knowledge about universal/standard precautions and
      ICP. RESULTS: Many ICP items had significant association with age, specialty for
      oral surgery, number of patients treated per day, willingness to treat HIV/AIDS
      patients and knowledge about the universal/standard precautions. In logistic
      regression model, knowledge about the precautions had significant associations
      with all ICP items. Among participants with disadvantageous characteristic group
      for ICP (ie, age >=50 years, being general dentist, and treating <=35
      patients/day), knowledge about the universal/standard precautions had greater
      impact on exchanging handpiece for each patient and installing extra-oral vacuum
      in those with age of >=50 years than in those who visited <=35 patient per day.
      CONCLUSION: Knowledge about the meaning of universal/standard precautions is the
      most significant predictor of compliance with ICPs among Japanese dentists.

PMID- 24463799
TI  - Psychosocial factors at work and blood-borne exposure among nurses.
AB  - BACKGROUND: Exposure to human blood and body fluids is a common risk for nurses.
      Many factors can affect the prevalence and incidence of this occupational hazard.
      Psychosocial factors at work may be a risk factor for the exposure. OBJECTIVE: To
      assess needle stick, sharp injury and mucus exposure to blood-borne pathogens
      among nurses in Iran and to determine the association between these exposures and
      psychosocial factors at work. METHODS: A cross-sectional study was conducted on
      nurses in a public hospital, Tehran, Iran. 364 nurses received and 339 completed
      and returned a self-reported questionnaire containing demographic data, history
      of exposure to blood-borne pathogens at work during previous year and the General
      Nordic questionnaire for psychological and social factors at work (QPS Nordic 34+
      Questionnaire). RESULTS: Of 339 participants, 197 (58.1%) reported needle-stick
      injury, 186 (54.6%) reported another type of sharp injury, and 112 (33%) reported
      a mucous membrane exposure during the previous year. More than half of the
      participants who had history of exposure, had not reported it. Those with middle
      or high level of stress had higher crude and adjusted odds than those with lower
      stress for all kinds of exposure. Adjusted odds ratios for high stress group
      (ranging from 2.8 to 4.4) were statistically different from 1. CONCLUSION: There
      is a high prevalence of needle-stick and sharp injury and mucous membrane
      exposure to patients' blood or body fluids among studied nurses. There is a
      significant association between increasing psychosocial factors at work and
      exposure to blood-borne pathogens among this group of nurses.

PMID- 24463800
TI  - Compliance to occupational safety measures among the paramedical workers in a
      tertiary hospital in Karnataka, South India.
AB  - BACKGROUND: The guidelines for minimizing occupational health risk from exposure
      to highly infectious diseases is already established but little information
      exists on the compliance of these measures among paramedical workers in India.
      OBJECTIVE: To study the awareness of occupational safety measures such as
      universal precautions, biomedical waste handling, disposal and its compliance in
      their daily practice. METHODS: A hospital-based cross-sectional study was
      undertaken in a tertiary private hospital in Karnataka, Bangalore, India. Data
      was collected using a pretested and predesigned proforma from 120 respondents: 85
      nurses and 35 laboratory technicians. RESULTS: 27 (32%) nurses and 20 (57%)
      laboratory technicians could relate universal precautions to infection
      prevention. Only 6 (7%) nurses and 2 (6%) technicians had knowledge about proper
      hospital waste segregation. 45 (52.9%) nurses and 15 (42.8%) technicians had
      knowledge about post-exposure prophylaxis. 3 (4%) nurses and 9 (26%) technicians
      were formally trained in following universal precautions. Adequate hand washing
      was practiced among 17 (20%) nurses and none of the technicians. Faulty practice
      such as recapping of needle was prevalent among 57 (67%) nurses and 29 (83%)
      technicians. 32 (38%) nurses and 10 (29%) technicians received hepatitis B
      vaccine. CONCLUSION: As knowledge and practice regarding different aspects of
      universal precautions was not satisfactory, training was warranted urgently in
      the study population. Also, suggestions were made to develop and implement
      institutional policies on the universal precautions and ensuring supply of
      personal protection equipment.

PMID- 24463801
TI  - Prevalence of hepatitis B vaccination among health care workers in Nigeria in
      2011-12.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is an endemic infection in Nigeria.
      Health care workers (HCWs) are at risk of occupational exposures to HBV-infected
      blood and body fluids. OBJECTIVE: To determine the prevalence and determinants of
      HBV vaccine coverage among HCWs in two teaching hospitals in Nigeria. METHODS:
      This cross-sectional study was undertaken in 2011 and 2012 in two teaching
      hospitals in Jos, North-Central Nigeria, and Yenagoa, South-South Nigeria. A self
      administered structured questionnaire was administered to HCWs to obtain socio
      demographic data and history of HBV vaccination. RESULTS: Out of 290 HCWs who
      participated in the study, 185 (64.5%) had received at least one dose of HBV
      vaccine; 105 (36.2%) had full coverage of three doses. Professional category and
      previous training in infection control were independently associated with HBV
      vaccination. House officers and laboratory scientists were more likely to be
      unvaccinated than resident doctors, consultant doctors and nurses. Full vaccine
      coverage was associated with younger age and shorter years of professional
      experience. CONCLUSION: We observed a generally low rate of HBV vaccine coverage
      among HCWs in Nigeria. Establishment of policies on compulsory HBV vaccination of
      all HCWs in Nigeria is recommended.

PMID- 24463802
TI  - Occupational blood exposure among health care personnel and hospital trainees.
AB  - Blood and body fluid Exposure is a major occupational safety problems for health
      care workers. Therefor We conducted a descriptive and retrospective study to
      identify the characteristics of blood exposure accidents in health care settings
      which lasted five years (2005-2009) at the two university hospitals of Sfax. We
      have 593 blood exposure accidents in health care settings 152 (25.6%) health
      personnel and 441 (74.4%) trainees' doctors, nurses and health technicians. The
      mechanism of blood and body fluid exposure was accidental needle-stick injury in
      78.9% of health staff, and 81% of trainees, accidental cut in 14.7% of health
      workers and 10.2% of trainees. The increasing severity of blood exposure
      accidents is linked to the lack of safe behavior against this risk. 

PMID- 24463803
TI  - Evaluation of children with Crimean-Congo hemorrhagic fever in the central
      Blacksea region.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is endemic in some regions of
      our country. It is seen in all age groups; however, its prevalance is low in
      children. The studies on CCHF have been mostly in adults. The aim of this study
      was to evaluate the epidemiologic, demographic, clinical and laboratory findings
      of children with CCHF. METHODS: Between May 2008 and September 2011, the medical
      records of patients who were admitted to the Children Infectious Diseases Service
      of Ondokuz Mayis University School of Medicine with positive blood IgM by enzyme
      linked immunosorbent assay or polymerase chain reaction positive for CCHF were
      retrospectively evaluated. Epidemiologic and demographic features, clinical and
      laboratory data and therapy were recorded. RESULTS: Fifty-four patients with the
      diagnosis of CCHF were recorded between May 2008 and September 2011. Main
      symptoms during hospital admission were fever (98%), vomiting (59%), headache
      (39%), nausea (39%), diarrhea (22%), abdominal pain (22%), bleeding (22%) and
      rash (20%). During admission, thrombocytopenia was found in 74%, elevated
      aspartate aminotransferase in 61%, leucopenia in 57%, elevated creatine kinase
      (33%) and alanine aminotransaminase (29%), and prolonged prothrombin time and
      partial thromboplastine time in 28% were noted. Thirty-nine patients received
      ribavirin treatment. During clinical follow up, bradycardia was recorded in 18
      patients (33%) all of whom received ribavirin treatment. One patient died.
      CONCLUSIONS: This study reports the largest series of children with CCHF and the
      first to describe bradycardia associated with ribavirin therapy.

PMID- 24463804
TI  - Dermatological spectrum of hand, foot and mouth disease from classical to
      generalized exanthema.
AB  - BACKGROUND: Hand, foot and mouth disease (HFMD) is classically defined as a
      childhood fever accompanied by a rash with vesicles or erosions of the oral
      mucosa, hands, feet and sometimes the buttocks. Severe neurological complications
      are associated with enterovirus 71 outbreaks in Asia. Recently, it has been
      suggested that HFMD is related to coxsackie virus A6 (CV-A6) when there is an
      atypical rash. The objective of the study is to determine the dermatological
      pattern of HFMD and to identify the virus serotypes associated with a specific
      dermatological pattern. METHODS: A prospective, cross-sectional study was
      conducted in 7 pediatric dermatology units in France from March 2010 to February
      2012. All children with clinically suspected diagnosis of HFMD were included.
      Clinical data were collected and swabs from the nasopharynx and vesicles were
      taken for reverse transcription polymerase chain reaction and genotyping. Only
      children with confirmed HFMD--defined by clinical diagnosis of HFMD and positive
      enterovirus polymerase chain reaction results--were included for analysis.
      RESULTS: One hundred and four children consulted for suspected HFMD, including 89
      (mean age: 25.7 months; sex ratio M/F 1.54) with confirmed HFMD. Seventy-eight
      (87.6%) had skin lesions on sites other than hand, feet and mouth. Thirty-seven
      (41.5%) had 5 or more anatomical sites involved (hand, feet and mouth, buttocks,
      legs, arms and trunk) considered as widespread exanthema. Widespread vesicular
      exanthema was observed with both CV-A6 and CV-A16. Peri-oral rash was associated
      with CV-A6 (P < 0.001). CONCLUSIONS: HFMD has a clinical spectrum ranging from
      classical to generalized vesicular exanthema. Generalized and atypical exanthema
      were observed with both CV-A6 and CV-A16 infections. CV-A6 is associated with
      peri-oral rash.

PMID- 24463805
TI  - The management and outcome of spinal implant-related infections in pediatric
      patients: a retrospective review.
AB  - BACKGROUND: Infection after implantation of spinal rods is a significant
      complication of this procedure. Optimal treatment of surgical implants often
      involves device removal. This approach is problematic when treating spinal
      implant-related infections, because device removal may cause significant
      morbidity. Medical management of these infections is therefore necessary, but
      treatment regimens are not standardized. We conducted a retrospective review of
      pediatric patients with spinal implant-related infections at a regional spinal
      center for a 6-year period. We describe clinical course, duration of treatment
      and outcomes. METHODS: We reviewed records of patients with spinal implant
      related infections from 2005 to 2010. Data collection included demographics,
      underlying diagnosis, surgical hardware, timing to infection after implantation,
      signs and symptoms of infection, duration of antimicrobials, adverse drug events
      and long-term outcomes. RESULTS: We enrolled 23 patients with spinal implant
      infections, aged 8-20 years. Wound drainage was the most common presenting
      symptom (82.6%). Median time from surgery to first infection was 16 days (range:
      8-1052 days). Median length of antimicrobial therapy was 131 days (range: 42-597
      days). Seventy eight percent were cured with antibiotics alone with implanted
      devices retained. Four patients failed medical therapy and required device
      removal. A wide range of antibiotic duration was used (42 to >597 days). Seven
      patients (30.4%) experienced at least 1 adverse drug event. CONCLUSIONS:
      Infection related to spinal instrumentation procedures can be managed medically
      with long-term antibiotic therapy. Careful monitoring for not only efficacy but
      also adverse drug events is advised. Further research is needed to determine the
      optimal duration of antibiotics for spinal implant-related infections.

PMID- 24463806
TI  - Trends in asymptomatic nasopharyngeal colonization with streptococcus pneumoniae
      after introduction of the 13-valent pneumococcal conjugate vaccine in Calgary,
      Canada.
AB  - BACKGROUND: We previously reported serotype-specific trends in pneumococcal
      nasopharyngeal colonization soon after introduction of the 7-valent pneumococcal
      conjugate vaccine (PCV7) in mid-2002. Our current aim is to describe later trends
      after PCV7 and early trends after PCV13 vaccine introduction in 2010. METHODS:
      The Calgary Area Streptococcus pneumoniae Epidemiology Research team conducted 10
      point-prevalence surveys of pneumococcal nasopharyngeal colonization in healthy
      children aged 12 and 18 months and 4.5 years biannually from 2003 to 2005
      (previously reported) and annually in 2006, 2010, 2011 and 2012. RESULTS: For
      surveys conducted during 2010-2012, the proportion colonized was 13.2% compared
      with 19.9% in surveys conducted during 2003-2006 (P < 0.001). Vaccination with 2
      or more doses of PCV7 or PCV13, older age and recent antibiotic use reduced the
      odds of colonization with any pneumococcus. By 2012, 94% of all isolates were
      nonvaccine serotypes with 11A, 15A/B/C, 22F, 23A/B and 35B/F representing 75% of
      all isolates. CONCLUSIONS: Pneumococcal nasopharyngeal colonization has changed
      profoundly since the introduction of conjugate vaccines and overall colonization
      by pneumococcus has declined in recent years. By 2012, nonvaccine serotypes have
      nearly completely replaced vaccine serotypes. The impact on clinical disease
      remains to be seen.

PMID- 24463807
TI  - A consensus statement: meningococcal disease among infants, children and
      adolescents in Latin America.
AB  - Invasive meningococcal disease is a serious infection that occurs worldwide.
      Neisseria meningitidis remains one of the leading causes of bacterial meningitis
      in all ages. Despite the availability of safe and effective vaccines against
      invasive meningococcal disease, few countries in Latin America implemented
      routine immunization programs with these vaccines. The Americas Health Foundation
      along with Fighting Infectious Disease in Emerging Countries recently sponsored a
      consensus conference. Six experts in infectious diseases from across the region
      addressed questions related to this topic and formulated the following
      recommendations: (1) standardized passive and active surveillance systems should
      be developed and carriage studies are mandatory; (2) a better understanding of
      the incidence, case fatality rates and prevalent serogroups in Latin America is
      needed; (3) countries should make greater use of the polymerase chain reaction
      assays to improve the sensitivity of diagnosis and surveillance of invasive
      meningococcal disease; (4) vaccines with broader coverage and more immunogenicity
      are desirable in young infants; (5) prevention strategies should include
      immunization of young infants and catch-up children and adolescents and (6)
      because of the crowded infant immunization schedule, the development of combined
      meningococcal vaccines and the coadministration with other infant vaccines should
      be explored. 

PMID- 24463808
TI  - Bordetella holmesii endocarditis: case report and review of literature.
AB  - The second case of Bordetella holmesii endocarditis in a pediatric patient is
      presented. This patient had a prosthetic mitral valve and asplenia. He was
      successfully treated with 6 weeks of intravenous meropenem. We review all 9 other
      reported cases of endocarditis and summarize treatment and outcome. Five were
      immunocompromised and 6 had predisposing cardiac conditions. 

PMID- 24463809
TI  - Five years of Kawasaki disease in the Netherlands: a national surveillance study.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence, disease
      presentation, treatment and cardiac outcome of Kawasaki disease (KD) in The
      Netherlands. METHODS: The national Dutch Pediatric Surveillance Unit was used to
      prospectively register new KD cases from 2008 through 2012. Questionnaires were
      sent to pediatricians to obtain clinical information. RESULTS: Nationwide 341
      cases were reported during the 5-year study period, of which 319 questionnaires
      (93.0%) were returned. The mean incidence of KD was estimated to be 5.8/100,000
      children <5 years of age. The median age at disease onset was 2.4 years (range
      0.1-14.6 years) and 79.2% of cases were <5 years of age. The male-to-female ratio
      was 1.5 to 1. Incomplete KD was diagnosed in 22.3% of cases and these cases were
      significantly younger than complete cases [median: 1.1 (0.1-13.7) vs. 2.8 (0.2
      14.6) years, P < 0.001]. In total, 308 patients (96.6%) received intravenous
      immunoglobulins (IVIG). Retreatment with IVIG was given in 71 (23.1%) and
      additional steroid treatment in 17 patients (5.5%). During the acute phase,
      coronary artery aneurysms developed in 43 cases (13.5%). Multivariate logistic
      regression analysis showed that male gender, delay of treatment (>10 days) and
      IVIG retreatment were independent risk factors for coronary artery aneurysms
      development. CONCLUSIONS: This prospective study of KD in The Netherlands
      revealed a mean annual incidence of 5.8/100,000 children <5 years of age.
      Clinicians should consider the diagnosis of KD in young (male) children with
      persistent inexplicable fever to start IVIG treatment within 10 days to prevent
      development of coronary artery aneurysms.

PMID- 24463810
TI  - Polymorphisms in IL-6, IL-10, TNF-alpha, IFN-gamma and TGF-beta1 genes and
      susceptibility to acute otitis media in early infancy.
AB  - BACKGROUND: Genetic susceptibility has a major role in the pathogenesis of acute
      otitis media (AOM). In the present study, we investigated the variability of 5
      cytokine genotypes as related to susceptibility and outcome of AOM in early
      infancy. METHODS: Single nucleotide polymorphisms in IL-6 (-174 G->C), IL-10 (
      592 C->A, -819 C->T and -1082 G->A), TNF-alpha (-308 G->A), IFN-gamma (+874 A->T)
      and TGF-beta1 (codon 10 C->T; codon 25 G->C) genes were investigated and related
      to clinical course and outcome in 96 infants younger than 9 months with AOM.
      RESULTS: Compared with wild genotypes, IL-10 (-592, -819 and -1082) and TGF-beta1
      (codon 10) genotypes carrying the alternative allele were related to more AOM
      episodes (P < 0.0001, P < 0.0001, P < 0.0001 and P = 0.002, respectively) and the
      need for tympanostomy tubes. Furthermore, IL-10 (-1082) and TGF-beta1 (codon 10)
      genotypes carrying the alternative allele were related to later onset of first
      AOM episode than wild-type genotypes (P = 0.007 and P = 0.039, respectively). No
      relationship was found about AOM complications. CONCLUSIONS: Our findings suggest
      that IL-10 and TGF-beta1 genotypes are related to the age of AOM onset, multiple
      AOM episodes and insertion of tympanostomy tubes, pointing to the involvement of
      anti-inflammatory cytokines in AOM during infancy.

PMID- 24463811
TI  - The inverse BAR domain protein IBARa drives membrane remodeling to control
      osmoregulation, phagocytosis and cytokinesis.
AB  - Here, we analyzed the single inverse Bin/Amphiphysin/Rvs (I-BAR) family member
      IBARa from Dictyostelium discoideum. The X-ray structure of the N-terminal I-BAR
      domain solved at 2.2 A resolution revealed an all-alpha-helical structure that
      self-associates into a 165-A zeppelin-shaped antiparallel dimer. The structural
      data are consistent with its shape in solution obtained by small-angle X-ray
      scattering. Cosedimentation, fluorescence anisotropy, and fluorescence and
      electron microscopy revealed that the I-BAR domain bound preferentially to
      phosphoinositide-containing vesicles and drove the formation of negatively curved
      tubules. Immunofluorescence labeling further showed accumulation of endogenous
      IBARa at the tips of filopodia, the rim of constricting phagocytic cups, in foci
      connecting dividing cells during the final stage of cytokinesis and most
      prominently at the osmoregulatory contractile vacuole (CV). Consistently, IBARa
      null mutants displayed defects in CV formation and discharge, growth,
      phagocytosis and mitotic cell division, whereas filopodia formation was not
      compromised. Of note, IBARa-null mutants were also strongly impaired in cell
      spreading. Taken together, these data suggest that IBARa constitutes an important
      regulator of numerous cellular processes intimately linked with the dynamic
      rearrangement of cellular membranes.

PMID- 24463812
TI  - The role of Hath6, a newly identified shear-stress-responsive transcription
      factor, in endothelial cell differentiation and function.
AB  - The key regulators of endothelial differentiation that is induced by shear stress
      are mostly unclear. Human atonal homolog 6 (Hath6 or ATOH8) is an endothelial
      selective and shear-stress-responsive transcription factor. In this study, we
      sought to elucidate the role of Hath6 in the endothelial specification of
      embryonic stem cells. In a stepwise human embryonic stem cell to endothelial cell
      (hESC-EC) induction system, Hath6 mRNA was upregulated synchronously with
      endothelial determination. Subsequently, gain-of-function and loss-of-function
      studies of Hath6 were performed using the hESC-EC induction model and endothelial
      cell lines. The overexpression of Hath6, which mimics shear stress treatment,
      resulted in an increased CD45(-)CD31(+)KDR(+) population, a higher tubular
      structure-formation capacity and increased endothelial-specific gene expression.
      By contrast, the knockdown of Hath6 mRNA markedly decreased endothelial
      differentiation. Hath6 also facilitated the maturation of endothelial cells in
      terms of endothelial gene expression, tubular-structure formation and cell
      migration. We further demonstrated that the gene encoding eNOS is a direct target
      of Hath6 through a reporter system assay and western blot analysis, and that the
      inhibition of eNOS diminishes hESC-EC differentiation. These results suggest that
      eNOS plays a key role in linking Hath6 to the endothelial phenotype. Further in
      situ hybridization studies in zebrafish and mouse embryos indicated that homologs
      of Hath6 are involved in vasculogenesis and angiogenesis. This study provides the
      first confirmation of the positive impact of Hath6 on human embryonic endothelial
      differentiation and function. Moreover, we present a potential signaling pathway
      through which shear stress stimulates endothelial differentiation. 

PMID- 24463813
TI  - Mutation of caspase-digestion sites in keratin 18 interferes with filament
      reorganization, and predisposes to hepatocyte necrosis and loss of membrane
      integrity.
AB  - Keratin 18 (K18 or KRT18) undergoes caspase-mediated cleavage during apoptosis,
      the significance of which is poorly understood. Here, we mutated the two caspase
      cleavage sites (D238E and D397E) in K18 (K18-DE), followed by transgenic
      overexpression of the resulting mutant. We found that K18-DE mice develop
      extensive Fas-mediated liver damage compared to wild-type mice overexpressing K18
      (K18-WT). Fas-stimulation of K18-WT mice or isolated hepatocytes caused K18
      degradation. By contrast, K18-DE livers or hepatocytes maintained intact keratins
      following Fas-stimulation, but showed hypo-phosphorylation at a major stress
      kinase-related keratin 8 (K8) phosphorylation site. Although K18-WT and K18-DE
      hepatocytes showed similar Fas-mediated caspase activation, K18-DE hepatocytes
      were more 'leaky' after a mild hypoosmotic challenge and were more susceptible to
      necrosis after Fas-stimulation or severe hypoosmotic stress. K8
      hypophosphorylation was not due to the inhibition of kinase binding to the
      keratin but was due to mutation-induced inaccessibility to the kinase that
      phosphorylates K8. A stress-modulated keratin phospho-mutant expressed in
      hepatocytes phenocopied the hepatocyte susceptibility to necrosis but was found
      to undergo keratin filament reorganization during apoptosis. Therefore, the
      caspase cleavage of keratins might promote keratin filament reorganization during
      apoptosis. Interference with keratin caspase cleavage shunts hepatocytes towards
      necrosis and increases liver injury through the inhibition of keratin
      phosphorylation. These findings might extend to other intermediate filament
      proteins that undergo proteolysis during apoptosis.

PMID- 24463814
TI  - An ancestral non-proteolytic role for presenilin proteins in multicellular
      development of the social amoeba Dictyostelium discoideum.
AB  - Mutations in either of two presenilin genes can cause familial Alzheimer's
      disease. Presenilins have both proteolysis-dependent functions, as components of
      the gamma-secretase complex, and proteolysis-independent functions in signalling.
      In this study, we investigate a conserved function of human presenilins in the
      development of the simple model organism Dictyostelium discoideum. We show that
      the block in Dictyostelium development caused by the ablation of both
      Dictyostelium presenilins is rescued by the expression of human presenilin 1,
      restoring the terminal differentiation of multiple cell types. This developmental
      role is independent of proteolytic activity, because the mutation of both
      catalytic aspartates does not affect presenilin ability to rescue development,
      and the ablation of nicastrin, a gamma-secretase component that is crucial for
      proteolytic activity, does not block development. The role of presenilins during
      Dictyostelium development is therefore independent of their proteolytic activity.
      However, presenilin loss in Dictyostelium results in elevated cyclic AMP (cAMP)
      levels and enhanced stimulation-induced calcium release, suggesting that
      presenilins regulate these intracellular signalling pathways. Our data suggest
      that presenilin proteins perform an ancient non-proteolytic role in regulating
      intracellular signalling and development, and that Dictyostelium is a useful
      model for analysing human presenilin function. 

PMID- 24463815
TI  - Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in
      3D collagen matrix.
AB  - The membrane-anchored collagenase membrane type 1 matrix metalloprotease (MT1
      MMP) has been shown to play an essential role during epithelial tubulogenesis in
      3D collagen matrices; however, its regulation during tubulogenesis is not
      understood. Here, we report that degradation of collagen in polarized epithelial
      cells is post-translationally regulated by changing the localization of MT1-MMP
      from the apical to the basal surface. MT1-MMP predominantly localizes at the
      apical surface in inert polarized epithelial cells, whereas treatment with HGF
      induced basal localization of MT1-MMP followed by collagen degradation. The basal
      localization of MT1-MMP requires the ectodomains of the enzyme because deletion
      of the MT-loop region or the hemopexin domain inhibited basal localization of the
      enzyme. TGFbeta is a well-known inhibitor of tubulogenesis and our data indicate
      that its mechanism of inhibition is, at least in part, due to inhibition of MT1
      MMP localization to the basal surface. Interestingly, however, the effect of
      TGFbeta was found to be bi-phasic: at high doses it effectively inhibited basal
      localization of MT1-MMP, whereas at lower doses tubulogenesis and basal
      localization of MT1-MMP was promoted. Taken together, these data indicate that
      basal localization of MT1-MMP is a key factor promoting the degradation of
      extracellular matrix by polarized epithelial cells, and that this is an essential
      part of epithelial morphogenesis in 3D collagen.

PMID- 24463816
TI  - Modulation of hypoxia-signaling pathways by extracellular linc-RoR.
AB  - Resistance to adverse environmental conditions, such as hypoxia, contributes to
      the reduced efficacy of anticancer therapies and tumor progression. Although
      deregulated expression of many long noncoding RNA (lncRNA) occurs in human
      cancers, the contribution of such RNA to tumor responses to hypoxia are unknown.
      RNA expression profiling identified several hypoxia-responsive lncRNAs, including
      the long intergenic noncoding RNA, regulator of reprogramming (linc-RoR), which
      is also increased in expression in malignant liver cancer cells. Linc-RoR
      expression was increased in hypoxic regions within tumor cell xenografts in vivo.
      Tumor cell viability during hypoxia was reduced by small interfering RNA (siRNA)
      to linc-RoR. Compared with controls, siRNA to linc-RoR decreased phosphorylation
      of p70S6K1 (RPS6KB1), PDK1 and HIF-1alpha protein expression and increased
      expression of the linc-RoR target microRNA-145 (miR-145). Linc-RoR was highly
      expressed in extracellular RNA released by hepatocellular cancer (HCC) cells
      during hypoxia. Incubation with extracellular vesicle preparations containing
      extracellular RNA increased linc-RoR, HIF-1alpha expression and cell survival in
      recipient cells. These studies show that linc-RoR is a hypoxia-responsive lncRNA
      that is functionally linked to hypoxia signaling in HCC through a miR-145-HIF
      1alpha signaling module. Furthermore, this work identifies a mechanistic role for
      the extracellular transfer of linc-RoR in intercellular signaling to promote cell
      survival during hypoxic stress.

PMID- 24463818
TI  - Organ-specific quality control of plant peroxisomes is mediated by autophagy.
AB  - Peroxisomes are essential organelles that are characterized by the possession of
      enzymes that produce hydrogen peroxide (H2O2) as part of their normal catalytic
      cycle. During the metabolic process, peroxisomal proteins are inevitably damaged
      by H2O2 and the integrity of the peroxisomes is impaired. Here, we show that
      autophagy, an intracellular process for vacuolar degradation, selectively
      degrades dysfunctional peroxisomes. Marked accumulation of peroxisomes was
      observed in the leaves but not roots of autophagy-related (ATG)-knockout
      Arabidopsis thaliana mutants. The peroxisomes in leaf cells contained markedly
      increased levels of catalase in an insoluble and inactive aggregate form. The
      chemically inducible complementation system in ATG5-knockout Arabidopsis provided
      the evidence that these accumulated peroxisomes were delivered to vacuoles for
      degradation by autophagy. Interestingly, autophagosomal membrane structures
      specifically recognized the abnormal peroxisomes at the site of the aggregates.
      Thus, autophagy is essential for the quality control of peroxisomes in leaves and
      for proper plant development under natural growth conditions.

PMID- 24463819
TI  - Epithelial repair is a two-stage process driven first by dying cells and then by
      their neighbours.
AB  - Epithelial cells maintain an essential barrier despite continuously undergoing
      mitosis and apoptosis. Biological and biophysical mechanisms have evolved to
      remove dying cells while maintaining that barrier. Cell extrusion is thought to
      be driven by a multicellular filamentous actin ring formed by neighbouring cells,
      the contraction of which provides the mechanical force for extrusion, with little
      or no contribution from the dying cell. Here, we use live confocal imaging,
      providing time-resolved three-dimensional observations of actomyosin dynamics, to
      reveal new mechanical roles for dying cells in their own extrusion from
      monolayers. Based on our observations, the clearance of dying cells can be
      subdivided into two stages. The first, previously unidentified, stage is driven
      by the dying cell, which exerts tension on its neighbours through the action of a
      cortical contractile F-actin and myosin ring at the cell apex. The second stage,
      consistent with previous studies, is driven by a multicellular F-actin ring in
      the neighbouring cells that moves from the apical to the basal plane to extrude
      the dying cell. Crucially, these data reinstate the dying cell as an active
      physical participant in cell extrusion.

PMID- 24463817
TI  - A central region of Gli2 regulates its localization to the primary cilium and
      transcriptional activity.
AB  - Signaling through vertebrate Hedgehog (Hh) proteins depends on the primary
      cilium. In response to Hh signals, the transcriptional activator of the pathway,
      Gli2, accumulates at the ciliary tip, raising the possibility that ciliary
      localization is important for Gli2 activation. To test this hypothesis, we used
      the Floxin system to create knock-in Gli2 alleles in embryonic stem cells (ESCs)
      to allow methodical testing of which domains and residues are essential for the
      ciliary localization of Gli2. The Gli2 zinc fingers, transcriptional activation
      domain, repressor domain, phosphorylation cluster and a Sufu binding motif were
      each dispensable for ciliary localization. Mutating residues that are required
      for Gli2 sumoylation and nuclear trafficking also did not abrogate ciliary
      localization. By contrast, several other domains restricted Gli2 nuclear
      localization, and a central region, distinct from previously characterized
      domains, was required for ciliary localization. In addition to an inability to
      localize to cilia, Gli2 lacking this central domain was unable to activate target
      genes. Thus, our systematic analysis in ESCs reveals that distinct regions of
      Gli2 regulate its nuclear and ciliary localization. The identification of a
      domain essential for both ciliary localization and transcriptional activity
      suggests that ciliary localization of Gli2 is required for its activation.

PMID- 24463820
TI  - AII amacrine cells discriminate between heterocellular and homocellular locations
      when assembling connexin36-containing gap junctions.
AB  - Electrical synapses (gap junctions) rapidly transmit signals between neurons and
      are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant
      isoform; however, the mechanisms underlying formation of Cx36-containing
      electrical synapses are unknown. We focus on homocellular and heterocellular gap
      junctions formed by an AII amacrine cell, a key interneuron found in all
      mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged
      with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP),
      heterocellular gap junctions formed between AII cells and ON cone bipolar cells
      are fully functional, whereas homocellular gap junctions between two AII cells
      are not formed. A tracer injected into an AII amacrine cell spreads into ON cone
      bipolar cells but is excluded from other AII cells. Reconstruction of Cx36-EGFP
      clusters on an AII cell in the KO-Cx36-EGFP genotype confirmed that the number,
      but not average size, of the clusters is reduced - as expected for AII cells
      lacking a subset of electrical synapses. Our studies indicate that some neurons
      exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest
      that employing different gap-junction-forming mechanisms could provide the means
      for a cell to regulate its gap junctions in a target-cell-specific manner, even
      if these junctions contain the same connexin.

PMID- 24463823
TI  - Addressing the plight of patients with kidney failure.

PMID- 24463821
TI  - Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic
      response to FGF2 in human endothelial cells.
AB  - MicroRNA-149 (miR-149) is located within the first intron of the glypican-1
      (GPC1) gene. GPC1 is a low affinity receptor for fibroblast growth factor (FGF2)
      that enhances FGF2 binding to its receptor (FGFR1), subsequently promoting FGF2
      FGFR1 activation and signaling. Using bioinformatic approaches, both GPC1 and
      FGFR1 were identified and subsequently validated as targets for miR-149 (both the
      mature strand, miR-149, and the passenger strand, miR-149*) in endothelial cells
      (ECs). As a consequence of their targeting activity towards GPC1 and FGFR1, both
      miR-149 and miR-149* regulated FGF2 signaling and FGF2-induced responses in ECs,
      namely proliferation, migration and cord formation. Moreover, lentiviral
      overexpression of miR-149 reduced in vivo tumor-induced neovascularization.
      Importantly, FGF2 transcriptionally stimulated the expression of miR-149
      independently of its host gene, therefore assuring the steady state of FGF2
      induced responses through the regulation of the GPC1-FGFR1 binary complex in ECs.

PMID- 24463824
TI  - Quality of care of patients with chronic kidney disease in national healthcare
      group polyclinics from 2007 to 2011.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is a major public health problem where
      majority of patients are managed in the primary care. The major risk factors are
      advanced age, hypertension and diabetes mellitus, and risk factors control is
      paramount to prevent progression to CKD. The objective of the study is to
      describe the epidemiology and quality of care of patients with CKD stages 3 to 5
      at National Healthcare Group Polyclinics (NHGP). MATERIALS AND METHODS: The study
      was carried out using data from National Healthcare Group (NHG) Renal Registry.
      Patients were included if they were identified to have CKD based on ICD-9-CM
      codes and laboratory results. RESULTS: Overall, the number of CKD patients
      increased more than 2 fold from 4734 in 2007 to 10,245 in 2011. In 2011, the
      majority belonged to stages 3A (39.6%) and 3B (37.6%), had hypertension (98.2%),
      dyslipidemia (97.2%) and diabetes mellitus (68.7%). From 2007 to 2011, among
      those with hypertension, the use of angiotensin converting enzyme (ACE)
      inhibitors and/ or angiotensin receptor blockers increased from 78.4% to 84.1%,
      and the percentage with good systolic blood pressure control (<130 mmHg) improved
      from 18.7% to 36.3%. Among those with dyslipidemia, the use of statins increased
      from 81% to 87.1%, and the percentage of patients with low density lipoproteins
      (LDL) <2.6 mmol/L increased from 40% to 54.7%. However, among those with diabetes
      mellitus, mean glycated haemoglobin (HBA1c) increased from 7.4% to 7.6%, and the
      percentage of patients with HBA1c <=7.0% decreased from 44.5% to 39.4%.
      CONCLUSION: The number of CKD patients in NHGP has increased significantly from
      2007 to 2011 at an average annual rate of 21.3%. Majority of patients the study
      conducted in 2011 were in stage 3A and stage 3B. Blood pressure and LDL control
      are encouraging but glycaemic control can be further improved.

PMID- 24463822
TI  - HDAC1 activates FoxO and is both sufficient and required for skeletal muscle
      atrophy.
AB  - The Forkhead box O (FoxO) transcription factors are activated, and necessary for
      the muscle atrophy, in several pathophysiological conditions, including muscle
      disuse and cancer cachexia. However, the mechanisms that lead to FoxO activation
      are not well defined. Recent data from our laboratory and others indicate that
      the activity of FoxO is repressed under basal conditions via reversible lysine
      acetylation, which becomes compromised during catabolic conditions. Therefore, we
      aimed to determine how histone deacetylase (HDAC) proteins contribute to
      activation of FoxO and induction of the muscle atrophy program. Through the use
      of various pharmacological inhibitors to block HDAC activity, we demonstrate that
      class I HDACs are key regulators of FoxO and the muscle-atrophy program during
      both nutrient deprivation and skeletal muscle disuse. Furthermore, we
      demonstrate, through the use of wild-type and dominant-negative HDAC1 expression
      plasmids, that HDAC1 is sufficient to activate FoxO and induce muscle fiber
      atrophy in vivo and is necessary for the atrophy of muscle fibers that is
      associated with muscle disuse. The ability of HDAC1 to cause muscle atrophy
      required its deacetylase activity and was linked to the induction of several
      atrophy genes by HDAC1, including atrogin-1, which required deacetylation of
      FoxO3a. Moreover, pharmacological inhibition of class I HDACs during muscle
      disuse, using MS-275, significantly attenuated both disuse muscle fiber atrophy
      and contractile dysfunction. Together, these data solidify the importance of
      class I HDACs in the muscle atrophy program and indicate that class I HDAC
      inhibitors are feasible countermeasures to impede muscle atrophy and weakness.

PMID- 24463825
TI  - Cancer among end-stage renal disease patients on dialysis.
AB  - INTRODUCTION: The aim of this study is to investigate the risk of cancer among
      end-stage renal disease (ESRD) patients on dialysis in Singapore. MATERIALS AND
      METHODS: The study looks at a retrospective cohort of 5505 ESRD patients who had
      received dialysis between 1998 and 2007. The cancer risk of these patients would
      be compared against the risk of the general population. RESULTS: During a median
      follow-up time of 3.9 years, 267 (4.9%) dialysis patients developed cancer. The
      risk of cancer (excluding non-melanoma skin cancer) is 1.66 times higher in
      dialysis patients than the general population, and is highest at age less than 35
      years old and at first year after dialysis. Cancer risk was found to be
      significantly higher among Chinese dialysis patients, followed by Malays,
      compared to the general population. The 3 sites with highest elevated cancer
      risks among dialysis patients compared to the general population are kidney,
      tongue and multiple myeloma. CONCLUSION: The finding of elevated cancer risk
      among younger dialysis patients is similar to other international studies. High
      cancer risks among specific cancer sites were also consistent with other studies.
      In view of the lack of screening procedures for these cancers and shortened
      expected survival of ESRD patients, cancer screening of ESRD patients should be
      individualised and based on a reasonable life expectancy and transplant
      candidacy, keeping in mind the competing risk of cardiovascular mortality.

PMID- 24463826
TI  - Right-siting chronic kidney disease care-a survey of general practitioners in
      Singapore.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is a major public health problem in
      Singapore. Efforts are being made to right-site CKD care (stage 1 to 3) from
      specialist outpatient clinics (SOCs) to general practitioners (GPs) to ease
      congestion. This study aims to identify factors influencing screening and
      management of CKD among GPs in Singapore. MATERIALS AND METHODS: A survey was
      conducted among the 1202 GPs between April and September 2010. The survey
      questionnaire was developed in collaboration with experts in nephrology and
      general practice, it included questions about screening, awareness and management
      of CKD. POPULATION STUDIED: GPs registered with the National Healthcare Group
      General Practitioner (NHG GP) partner database. RESULTS: Three hundred and two
      GPs completed the survey. A total of 70% of the respondents were males and with
      their median years of practice as 18. A total of 86% of them reported screening
      for CKD while 50% of GPs were confident of managing patients with CKD stage 1;
      and 38% of GPs are aware of CKD guidelines. Majority of GPs (64%) agreed that
      right-siting of early CKD patients would ease congestion at SOCs. Some of the
      obstacles in CKD management listed by the GPs were lack of patient trust,
      experience and communication with the specialist and the inability of the patient
      to pay. CONCLUSION: GPs screen patients for CKD, however their awareness of
      guidelines is limited. Opportunities exist for improving physician recognition of
      CKD, awareness of CKD guidelines, improving collaborative care and reimbursement
      for the patient and the provider. This study has identified factors which when
      addressed could lead to wider acceptance of CKD right-siting by both the patients
      and the GPs.

PMID- 24463827
TI  - What factors really matter? Health-related quality of life for patients on kidney
      transplant waiting list.
AB  - INTRODUCTION: Waiting times for kidney transplant are long in Singapore.
      Healthrelated quality of life (HRQoL) of patients might be affected as a result
      of the stress of the long wait and the uncertainty of being called to undergo a
      surgical operation. This study aimed to measure the HRQoL of patients on the
      kidney transplant waiting list and to identify factors which could impact on the
      HRQoL scores in this group of patients. MATERIALS AND METHODS: This was a cross
      sectional study of kidney transplant waiting list patients managed at a tertiary
      renal unit using the SF-36. A SF-36 normative calculator was used to generate
      HRQoL scores for the Singapore general population matched with the study cohort's
      age, gender and ethnicity. RESULTS: There were 265 respondents with a response
      rate was 81%. Our study shows that HRQoL scores for the kidney transplant waiting
      list patients were lower than the population norms across all subscales and were
      clinically significant for General Health, Role Physical, Bodily Pain, Social
      Functioning and Mental Component Summary scores. Factors such as being Chinese,
      married, employed and undergoing haemodialysis predicted better HRQoL scores
      after adjusting for possible confounders. Age, gender, educational level,
      household income, history of kidney transplant, duration on the transplant
      waiting list and years on dialysis did not significantly influence SF-36 across
      all subscales scores. CONCLUSION: Kidney transplant waiting list patients had
      worse HRQoL compared to the general population. Factors such as ethnicity,
      marital status, employment status, and type of dialysis treatment significantly
      influenced patients' perception of their HRQoL.

PMID- 24463828
TI  - Risk factors and time-trends of cytomegalovirus (CMV), syphilis, toxoplasmosis
      and viral hepatitis infection and seroprevalence in human immunodeficiency virus
      (HIV) infected patients.
AB  - INTRODUCTION: Chronic bacterial, viral and parasitic infections contribute to the
      morbidity and mortality associated with human immunodeficiency virus (HIV)
      infection. This study investigated risk factors and time-trends of the
      seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total
      antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly
      diagnosed HIV individuals in Singapore. MATERIALS AND METHODS: This was a cross
      sectional study. A random sample of 50% of HIV infected patients who visited the
      Communicable Disease Centre (CDC), Singapore for first-time care from January
      2006 to December 2011 were analysed. RESULTS: Among the 793 study subjects, 93.4%
      were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was
      41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm3. The
      prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and
      toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%;
      hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C,
      73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was
      significantly more common among men who have sex with men (MSM) (multivariate OR:
      2.53, 95% CI, 1.31 to 4.90, P = 0.006). CONCLUSION: This study described the
      baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore,
      and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates
      compared to the general population may have important consequences for disease
      progression, response to antiretroviral treatment and long-term general health.

PMID- 24463830
TI  - Habituation following tinnitus retraining therapy in tinnitus sufferers.
AB  - INTRODUCTION: This study evaluated the efficacy of tinnitus retraining therapy
      (TRT) in habituating patients with tinnitus. MATERIALS AND METHODS: This is a
      retrospective review of patients who underwent TRT in a tertiary referral
      Otorhinolaryngology unit. Patients were followed up with structured interviews
      with the aid of questionnaire forms. Habituation following TRT was evaluated.
      RESULTS: A total of 702 patients were included (55% male, 45% female).
      Habituation of reaction to tinnitus and habituation of perception were analysed.
      Average duration of follow up was 33 months. In total, 68% of patients described
      improvement in annoyance following TRT. Of these patients, 80% of them described
      habituation of perception as well. There was no statistical difference in gender
      and age between patients who did and did not respond to TRT. However, duration of
      treatment was significantly longer in patients who habituated (P <0.05). Patients
      who adopted treatment strategies recommended based on Jastreboff's TRT categories
      were also found to have higher success rates compared to those who refused.
      CONCLUSION: The goal of TRT is to achieve habituation of reaction to tinnitus.
      Habituation of perception is often a secondary result of sufficiently habituated
      response. From our study, more than two thirds of patients with tinnitus achieved
      habituation of reaction and of these, the majority also habituated to awareness
      of the tinnitus.

PMID- 24463829
TI  - Genomics and disease progression in IgA nephritis.
AB  - Apart from clinical, histological and biochemical indices, genomics are now being
      employed to unravel the pathogenetic mechanisms in the disease progression of IgA
      nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene
      polymorphism have been controversial. Those patients with the DD genotype seem to
      have a poorer prognosis. However, with high dose angiotensin receptor blocker
      (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a
      matter for concern as those with the DD genotype would also respond favourably to
      high dose ARB therapy. Association studies with gene sequencing and haplotypes
      have suggested that multiple genes are involved in the pathogenesis of IgAN. Some
      workers have reported a synergistic effect in the combined analysis of AGT-M235T
      and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA)
      microarray, tens of thousands of gene expressions genome-wide can be examined
      together simultaneously. A locus of familial IgAN has been described with strong
      evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported
      at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the
      identification of specific pathogenic genes that are up- or down-regulated and
      this may allow genome wide analyses of these genes and their role in the
      pathogenesis and progression of IgAN. Recently, using genome-wide association
      studies (GWAS) more loci for disease susceptibility for IgAN have been identified
      at 17p13, 8p23, 22q12, 1q32 and 6p21. 

PMID- 24463831
TI  - Haze and dengue: the unanswered questions.

PMID- 24463832
TI  - Renal replacement therapy: why patients say "no".

PMID- 24463834
TI  - Challenges of dengue control.

PMID- 24463833
TI  - Acute kidney injury (AKI) with the use of antibiotic-impregnated bone cement in
      primary total knee arthroplasty.

PMID- 24463835
TI  - A misplaced kidney in a middle-aged woman.

PMID- 24463836
TI  - Purple urine bag syndrome (PUBS): an unusual and rare manifestation of a common
      condition.

PMID- 24463837
TI  - A fair and just society: what stays, what changes?

PMID- 24463838
TI  - 10th college of physicians lecture: the challenges of reinventing medical
      generalism in the 21st century.

PMID- 24463839
TI  - Comparison of Thraustochytrids Aurantiochytrium sp., Schizochytrium sp.,
      Thraustochytrium sp., and Ulkenia sp. for production of biodiesel, long-chain
      omega-3 oils, and exopolysaccharide.
AB  - Heterotrophic growth of thraustochytrids has potential in coproducing biodiesel
      for transportation, as well as producing a feedstock for omega-3 long-chain
      (>=C20) polyunsaturated fatty acids (LC-PUFA), especially docosahexaenoic acid
      (DHA) for use in nutraceuticals. In this study, we compared eight new endemic
      Australian thraustochytrid strains from the genera Aurantiochytrium,
      Schizochytrium, Thraustochytrium, and Ulkenia for the synthesis of
      exopolysaccharide (EPS), in addition to biodiesel and LC-PUFA. Aurantiochytrium
      sp. strains readily utilized glucose for biomass production, and increasing
      glucose from 2 to 4 % w/v of the culture medium resulted in increased biomass
      yield by an average factor of 1.7. Ulkenia sp. strain TC 010 and Thraustochytrium
      sp. strain TC 033 did not utilize glucose, while Schizochytrium sp. strain TC 002
      utilized less than half the glucose available by day 14, and Thraustochytrium sp.
      strain TC 004 utilized glucose at 4 % w/v but not 2 % w/v of the culture
      suggesting a threshold requirement between these values. Across all strains,
      increasing glucose from 2 to 4 % w/v of the culture medium resulted in increased
      total fatty acid methyl ester content by an average factor of 1.9. Despite an
      increasing literature demonstrating the capacity of thraustochytrids for DHA
      synthesis, the production of EPS from these organisms is not well documented. A
      broad range of EPS yields was observed. The maximum yield of EPS was observed for
      Schizochytrium sp. strain TC 002 (299 mg/L). High biomass-producing strains that
      also have high lipid and high EPS yield may be better candidates for commercial
      production of biofuels and other coproducts.

PMID- 24463840
TI  - The asymmetric dimethylarginine level is associated with the predicted stroke
      risk in Japanese women.
AB  - AIM: Asymmetric dimethylarginine(ADMA) has recently been investigated as a risk
      marker for cardio- and cerebrovascular diseases. However, it is not currently
      known whether the ADMA levels are related to the risk of stroke in Japanese
      women. METHODS: We examined 192 Japanese women(mean age, 55+/-9 years, range, 40
      80 years) who underwent health examinations. The ADMA level and various vascular
      risk factors of each subject were assessed, and the predicted 10-year stroke risk
      was calculated using the point-based prediction model provided by the Japan
      Public Health Center study. RESULTS: In a correlation coefficient analysis, age
      was found to be the only factor significantly correlated with the ADMA level. A
      significant odds ratio (OR) for a high predicted stroke risk(10-year risk, >=5%)
      was noted in the highest ADMA level tertile(6.24; 95% CI, 1.13-34.5; p=0.036)
      compared with the lowest tertile, after adjusting for potential confounding
      factors. A significant OR for a high predicted stroke risk was also found for
      each increment in the ADMA tertile and standard deviation(adjusted OR, 2.42; 95%
      CI, 1.09-5.34; p=0.029; and 2.51; 95% CI, 1.24-5.11; p=0.011, respectively).
      CONCLUSIONS: An elevated ADMA level is significantly associated with an increased
      predicted stroke risk, suggesting that measuring the ADMA level is useful for
      identifying Japanese women with an elevated stroke risk.

PMID- 24463842
TI  - Red blood cell fatigue evaluation based on the close-encountering point between
      extensibility and recoverability.
AB  - Red blood cells (RBC) circulate the human body several hundred thousand times in
      their life span. Therefore, their deformability is really important, especially
      when they pass through a local capillary whose diameter can be as narrow as 3
      MUm. While there have been a number of works discussing the deformability in a
      simulated capillary such as a microchannel, as far as we examined in the
      literature, no work focusing on the change of shape after reciprocated mechanical
      stress has been reported so far. One of the reasons is that there have been no
      appropriate experimental systems to achieve such a test. This paper presents a
      new concept of RBC fatigue evaluation. The fatigue state is defined by the time
      of reciprocated mechanical stress when the extensibility and the recoverability
      characteristics meet each other. Our challenge is how to construct a system
      capable of achieving stable and accurate control of RBCs in a microchannel. For
      this purpose, we newly introduced two fundamental components. One is a robotic
      pump capable of manipulating a cell in the accuracy of +/-0.24 MUm in an
      equilibrium state with a maximum response time of 15 ms. The other is an online
      high speed camera capable of chasing the position of RBCs with a sampling rate of
      1 kHz. By utilizing these components, we could achieve continuous observation of
      the length of a RBC over a 1000 times reciprocated mechanical stress. Through
      these experiments, we found that the repeat number that results in the fatigue
      state has a close correlation with extensibility. 

PMID- 24463841
TI  - Validity of a Web-based educational program to disseminate a standardized bowel
      preparation rating scale.
AB  - GOALS: Our goal was to assess the validity of a Web-based educational program on
      the Boston Bowel Preparation Scale (BBPS). BACKGROUND: Data on Web-based
      education for improving the practice and quality of colonoscopy are limited.
      STUDY: Endoscopists worldwide participated in the BBPS Educational Program. We
      assessed program completion rates, satisfaction, short-term (0 to 90 d) and long
      term (91 to 180 d) uptake of the BBPS, and the validity of the program by
      measuring the reliability of the BBPS among participants. RESULTS: A total of 207
      endoscopists completed the program. Overall, 93% found the content relevant, 89%
      felt confident in using the BBPS, and 97% thought the quality was good or
      excellent. Uptake of the BBPS into clinical practice was robust with 91% and 98%
      of colonoscopy reports containing the BBPS at short-term and long-term follow-up,
      respectively. The interobserver and test-retest reliability of BBPS segment and
      total scores were both substantial. CONCLUSIONS: A BBPS Web-based educational
      program facilitates adoption into clinical practice and teaches the BBPS to be
      used reliably by a diverse group of endoscopists worldwide.

PMID- 24463843
TI  - Remodeling pattern is related to the degree of coronary plaque regression induced
      by pitavastatin: a sub-analysis of the TOGETHAR trial with intravascular
      ultrasound and coronary angioscopy.
AB  - This study aimed to clarify the relationships between arterial remodeling
      patterns and plaque volume regression or stabilization. The TOGETHAR trial is a
      prospective open-label trial designed to assess coronary plaque regression and
      stabilization with multiple plaque imaging modalities following 52 weeks of
      pitavastatin treatment (2 mg/day). Coronary plaques were observed in 46 patients
      with both angioscopy and intravascular ultrasound at baseline and after 52 weeks
      of drug treatment. We divided these patients into three groups according to their
      remodeling indices (RI). Group P consisted of patients with a baseline RI >1.05,
      Group M of patients with a baseline RI of 0.95-1.05, and Group N of patients with
      a baseline RI <0.95 and then evaluated differences in coronary plaque volume
      changes and yellow grade among the three groups. In the positive remodeling
      group, whose remodeling index (RI) exceeded 1.05 at baseline, RI and percent
      atheroma volume (PAV) were significantly reduced (RI 1.14 +/- 0.07 to 1.05 +/-
      0.10, p = 0.010, PAV 47.3 +/- 8.3 to 45.3 +/- 7.3 mm(3), p = 0.048). There was no
      relationship between baseline RI and the change in yellow grade of plaque. RI
      increased without significant change of PAV or a decrease in lumen volume in
      group N, with RI below 0.95 at baseline. Plaques with positive remodeling were
      more likely to have plaque volume regression by pitavastatin than those without
      in patients with coronary artery disease. Moreover, plaques with positive and
      negative remodeling were changed into those with intermediate remodeling by
      pitavastatin. Pitavastatin might induce not only plaque regression or
      stabilization, but also conformational normalization of vessel structure.

PMID- 24463844
TI  - Serum cholinesterase is an important prognostic factor in chronic heart failure.
AB  - We determine the importance of indicators of nutrition including lymphocyte,
      total protein, albumin, cholinesterase and body mass index, and compare the
      prognostic significance in chronic heart failure (CHF). We examined consecutive
      465 CHF patients (376 males, age 62 +/- 14 years) who underwent cardiopulmonary
      exercise testing, echocardiography and blood examination including indicators of
      nutrition at the same time in our hospital. The patients were followed up [median
      period 766 days (interquartile range 500-1060)] to register cardiac deaths and
      rehospitalization due to worsening heart failure. There were 180 cardiac events
      during the follow-up periods. Patients with cardiac events had lower
      cholinesterase level than those without events (P < 0.001). On the receiver
      operating characteristic analysis, the best cut-off value for cholinesterase was
      240 U/l (area under the curve 0.720). In the Kaplan-Meier analysis, patients with
      cholinesterase <240 U/l had significantly higher cardiac event rates than those
      with cholinesterase >240 U/l. Multivariable Cox proportional hazards model
      demonstrated that NYHA class III [hazard ratio (HR): 1.688, 95 % confidence
      interval (CI) 1.062-2.684, P = 0.027], eGFR (HR: 0.983, 95 % CI 0.971-0.995, P =
      0.006), sodium concentration (HR: 0.947, 95 % CI 0.897-0.999, P < 0.046), log BNP
      (HR: 1.880, 95 % CI 1.509-2.341, P < 0.001), cholinesterase (HR: 0.996, 95 % CI
      0.993-0.998, P = 0.002) and exertional periodic breathing (HR: 1.619, 95 % CI
      1.098-2.388, P = 0.015) were independent factors to predict adverse clinical
      outcomes. Serum cholinesterase level was an important prognostic factor in CHF.

PMID- 24463845
TI  - Evaluation of repolarization dynamics using the QT-RR regression line slope and
      intercept relationship during 24-h Holter ECG.
AB  - QT-RR linear regression consists of two parameters, slope and intercept, and the
      aim of this study was to evaluate repolarization dynamics using the QT-RR linear
      regression slope and intercept relationship during 24-h Holter ECG. This study
      included 466 healthy subjects (54.6 +/- 14.6 years; 200 men and 266 women) and 17
      patients with ventricular arrhythmias, consisted of 10 patients with idiopathic
      ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT
      and RR intervals were measured from ECG waves based on a 15-s averaged ECG during
      24-h Holter recording using an automatic QT analyzing system. The QT interval
      dependence on the RR interval was analyzed using a linear regression line for
      each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept).
      The slope of the QT-RR regression line in healthy subjects was significantly
      greater in women than in men (0.185 +/- 0.036 vs. 0.161 +/- 0.033, p < 0.001) and
      the intercept was significantly smaller in women than in men (0.229 +/- 0.028 vs.
      0.240 +/- 0.027, p < 0.001). A scatter diagram of the QT-RR regression line slope
      and intercept among healthy subjects demonstrated a statistically significant
      negative correlation (B = -0.62A + 0.34, r = -0.79). Distribution of both scatter
      diagrams of the slope and the intercept of the QT-RR regression line in patients
      with IVF and TDP was different from healthy subjects (left corner for IVF and
      upward shift for TDP). The slope and intercept relationship of the QT-RR linear
      regression line based on 24-h Holter ECG may become a simple useful marker for
      abnormality of ventricular repolarization dynamics.

PMID- 24463847
TI  - Decline in extractable kitasamycin during the composting of kitasamycin
      manufacturing waste with dairy manure and sawdust.
AB  - The aim of this study was to propose a feasible treatment of kitasamycin
      manufacturing waste by examining extractable kitasamycin and evaluating its
      compost maturity during the composting of waste with different ratios of dairy
      manure and sawdust over a 40-day period (volume/volume/volume; M1, 0/80/20; M2,
      10/70/20; and M3, 30/50/20). During composting, the concentration of extractable
      kitasamycin in kitasamycin-contaminated composts declined rapidly, and was
      undetectable in M2 within 15 days. M2 also achieved the highest fertility
      compost, which was characterised by the following final parameters: electrical
      conductivity, 2.34 dS cm(-1); pH, 8.15; total C/N, 22.2; water-soluble NH4(+), P,
      and K, 0.37, 3.43, and 1.05 g kg(-1), respectively; and plant germination index
      values, 92%. Furthermore, DGGE analysis showed a dramatic increase in the
      diversity of bacterial species during composting. In contrast, a high
      concentration (121 mg kg(-1)) of extractable kitasamycin still remained in the M3
      compost, which exerted an inhibitory effect on the composting, resulting in
      reduced bacterial diversity, high values of electrical conductivity and water
      soluble NH4(+), a low C/N ratio, and a low plant germination index value.
      Furthermore, 3.86 log (CFU g(-1)) kitasamycin-resistant bacteria were still
      present on day 40, indicating the biological degradation contributed to the
      decline of extractable kitasamycin. 

PMID- 24463846
TI  - Comparison of contemporary risk scores for predicting outcomes after surgery for
      active infective endocarditis.
AB  - Decision making regarding surgery for acute bacterial endocarditis is complex
      given its heterogeneity and often fatal course. Few studies have investigated the
      utility of operative risk scores in this setting. Endocarditis-specific scores
      have recently been developed. We assessed the prognostic utility of contemporary
      risk scores for mortality and morbidity after endocarditis surgery. Additive and
      logistic EuroSCORE I, EuroSCORE II, additive Society of Thoracic Surgeon's (STS)
      Endocarditis Score and additive De Feo-Cotrufo Score were retrospectively
      calculated for patients undergoing surgery for endocarditis during 2005-2011. Pre
      specified primary outcomes were operative mortality, composite morbidity and
      mortality during follow-up. A total of 146 patients were included with an
      operative mortality of 6.8 % followed for 4.1 +/- 2.4 years. Mean scores were
      additive EuroSCORE I: 8.0 +/- 2.5, logistic EuroSCORE I: 13.2 +/- 10.1 %,
      EuroSCORE II: 9.1 % +/- 9.4 %, STS Score: 32.2 +/- 13.5 and De Feo-Cotrufo Score:
      14.6 +/- 9.2. Corresponding areas under curve (AUC) for operative mortality
      0.653, 0.645, 0.656, 0.699 and 0.744; for composite morbidity were 0.623, 0.625,
      0.720, 0.714 and 0.774; and long-term mortality 0.588, 0.579, 0.686, 0.735 and
      0.751. The best tool for post-operative stroke was EuroSCORE II: AUC 0.837; for
      ventilation >24 h and return to theatre the De Feo-Cotrufo Scores were: AUC 0.821
      and 0.712. Pre-operative inotrope or intra-aortic balloon pump treatment,
      previous coronary bypass grafting and dialysis were independent predictors of
      operative and long-term mortality. In conclusion, risk models developed
      specifically from endocarditis surgeries and incorporating endocarditis variables
      have improved prognostic ability of outcomes, and can play an important role in
      the decision making towards surgery for endocarditis. 

PMID- 24463848
TI  - Effects of long-term grazing disturbance on the belowground storage of organic
      carbon in the Patagonian Monte, Argentina.
AB  - The objective of this study was to analyze the effect of grazing disturbance on
      the amount and the spatial distribution (vertical and horizontal) of root biomass
      and soil organic carbon (SOC) in order to evaluate whether grazing alters the
      belowground storage of organic carbon (C) in arid rangelands of the Patagonian
      Monte. We selected three representative sites (3 ha each) with low, moderate and
      high grazing disturbance located far, mid-distance and near the watering point,
      respectively, in rangelands submitted to sheep grazing for more than 100 years.
      We assessed the canopy structure and identified the four most frequent plant
      patch types at each site. We selected four replications of each patch type and
      extracted a soil sample (0-30 cm depth) underneath the canopy and in the middle
      of the nearest inter-patch bare soil area in winter and summer. We assessed the
      root and soil dry mass and the respective organic C concentration in each sample
      and then we estimated the total belowground organic C storage at each site. Total
      plant and perennial grass cover were lower with high than low grazing disturbance
      while the reverse occurred with dwarf shrub cover. High grazing disturbance led
      to the increase in total root biomass in the whole soil profile of patch areas
      and in the upper soil of inter-patch areas. SOC was higher in patch than in inter
      patch areas at all sites but at both areas was reduced with high grazing
      disturbance. This was probably the result of the low total plant cover and the
      low and recalcitrant contribution of above and below-ground plant litter to soils
      at sites with high grazing disturbance. Accordingly, these changes did not result
      in variations in the total belowground organic C storage. We concluded that high
      grazing disturbance did not affect the total belowground organic C storage but
      led to changes in the spatial patterning of this organic C storage (i.e shifting
      from soil to roots). 

PMID- 24463849
TI  - Mowing regime has different effects on reed stands in relation to habitat.
AB  - Reed (Phragmites australis) is widespread in aquatic habitats in Europe where it
      plays an important ecological role, especially as stabilizer of lake and river
      shores and as filter against pollutants. Reed is also abundant in ecotones
      towards terrestrial habitats, especially fen meadows, where its expansion can out
      compete rare slowly-growing fen species. Therefore, defining appropriate
      guidelines for managing reed in wetlands has to consider differences in the
      ecological roles that reed plays in different wetland habitats. In a small pre
      alpine lake in N Italy, we mowed reed stands in three plant communities located
      along a transect from the lake shore to the periphery. In each community, three
      areas were subjected to reed mowing in late winter, as traditionally done in the
      past. Three additional areas were subjected to mowing in winter and summer, while
      three areas served as un-treated controls. Summer mowing was carried out in
      August, when the nesting period of birds was concluded. Mowing in winter did not
      affect reed aboveground biomass (RAB) in any community but enhanced the
      efficiency of removing nutrients by reducing litter accumulation in the soil.
      Mowing in winter and summer only slightly decreased RAB in the riparian
      community, not at all in the intermediate community but significantly diminished
      RAB in fen meadows. Phosphorus deficiency and/or reduced competition with other
      species probably accounted for RAB reduction in fen meadows. In conclusion,
      winter mowing can be overall recommended for preventing eutrophication of
      littoral habitats while summer mowing is advisable for preventing reed expansion
      in fen meadows. However, the timing of summer mowing has to be defined
      considering all requirements needed for optimal management of each individual
      site. 

PMID- 24463850
TI  - Sectional analysis of the pollutant wash-off process based on runoff hydrograph.
AB  - The validity of using rainfall characteristics as lumped parameters for
      investigating the pollutant wash-off process such as first flush occurrence is
      questionable. This research study introduces an innovative concept of using
      sector parameters to investigate the relationship between the pollutant wash-off
      process and different sectors of the runoff hydrograph and rainfall hyetograph.
      The research outcomes indicated that rainfall depth and rainfall intensity are
      two key rainfall characteristics which influence the wash-off process compared to
      the antecedent dry period. Additionally, the rainfall pattern also plays a
      critical role in the wash-off process and is independent of the catchment
      characteristics. The knowledge created through this research study provides the
      ability to select appropriate rainfall events for stormwater quality treatment
      design based on the required treatment outcomes such as the need to target
      different sectors of the runoff hydrograph or pollutant species. The study
      outcomes can also contribute to enhancing stormwater quality modelling and
      prediction in view of the fact that conventional approaches to stormwater quality
      estimation is primarily based on rainfall intensity rather than considering other
      rainfall parameters or solely based on stochastic approaches irrespective of the
      characteristics of the rainfall event. 

PMID- 24463851
TI  - Removal of phenolics from aqueous media using quaternised maize tassels.
AB  - This paper reports on the preparation and modification of powdered maize tassels
      with polydiallyldimethylammonium chloride (polyDADMAC). The modified tassel were
      applied for the removal of phenolic compounds from water, through adsorption. The
      effect of contact time, sorbent dose, pH of the sample and the adsorption
      capacity were investigated at fixed temperature (25  degrees C). The optimum pH
      was 6.0 and the uptake was more than 90% within the first 10 min of contact. The
      adsorption prescribed to Langmuir model of monolayer adsorption implying a
      chemisorption process. The adsorption capacities were found to be 7.09, 8.23,
      8.84 and 4.74 mg g(-1) for chlorobenzoic acid, 2,4,6-trichlorophenol, 2,4
      dichlorophenol and 1,2-dihyroxybenzene respectively. These were fairly higher
      than many other reported systems. The removal efficiency was found to be 75, 64,
      55 and 40% for Chlorobenzoic acid, 2,4,6-Trichlorophenol, 2,4-dichlorophenol and
      1,2-dihyroxybenzene, respectively. This proved that quaternised maize tassels can
      be used as an efficient adsorbent material for removal of phenolic compounds from
      water and wastewater. 

PMID- 24463852
TI  - Spatially dynamic forest management to sustain biodiversity and economic returns.
AB  - Production of marketed commodities and protection of biodiversity in natural
      systems often conflict and thus the continuously expanding human needs for more
      goods and benefits from global ecosystems urgently calls for strategies to
      resolve this conflict. In this paper, we addressed what is the potential of a
      forest landscape to simultaneously produce habitats for species and economic
      returns, and how the conflict between habitat availability and timber production
      varies among taxa. Secondly, we aimed at revealing an optimal combination of
      management regimes that maximizes habitat availability for given levels of
      economic returns. We used multi-objective optimization tools to analyze data from
      a boreal forest landscape consisting of about 30,000 forest stands simulated 50
      years into future. We included seven alternative management regimes, spanning
      from the recommended intensive forest management regime to complete set-aside of
      stands (protection), and ten different taxa representing a wide variety of
      habitat associations and social values. Our results demonstrate it is possible to
      achieve large improvements in habitat availability with little loss in economic
      returns. In general, providing dead-wood associated species with more habitats
      tended to be more expensive than providing requirements for other species. No
      management regime alone maximized habitat availability for the species, and
      systematic use of any single management regime resulted in considerable
      reductions in economic returns. Compared with an optimal combination of
      management regimes, a consistent application of the recommended management regime
      would result in 5% reduction in economic returns and up to 270% reduction in
      habitat availability. Thus, for all taxa a combination of management regimes was
      required to achieve the optimum. Refraining from silvicultural thinnings on a
      proportion of stands should be considered as a cost-effective management in
      commercial forests to reconcile the conflict between economic returns and habitat
      required by species associated with dead-wood. In general, a viable strategy to
      maintain biodiversity in production landscapes would be to diversify management
      regimes. Our results emphasize the importance of careful landscape level forest
      management planning because optimal combinations of management regimes were taxon
      specific. For cost-efficiency, the results call for balanced and correctly
      targeted strategies among habitat types. 

PMID- 24463853
TI  - Interaction of bipolaron with the H2O/O2 redox couple causes current hysteresis
      in organic thin-film transistors.
AB  - Hysteresis in the current-voltage characteristics is one of the major obstacles
      to the implementation of organic thin-film transistors in large-area integrated
      circuits. The hysteresis has been correlated either extrinsically to various
      charge-trapping/transfer mechanisms arising from gate dielectrics or surrounding
      ambience or intrinsically to the polaron-bipolaron reaction in low-mobility
      conjugated polymer thin-film transistors. However, a comprehensive understanding
      essential for developing viable solutions to eliminate hysteresis is yet to be
      established. By embedding carbon nanotubes in the polymer-based conduction
      channel of various lengths, here we show that the bipolaron
      formation/recombination combined with the H2O/O2 electrochemical reaction is
      responsible for the hysteresis in organic thin-film transistors. The bipolaron
      induced hysteresis is a thermally activated process with an apparent activation
      energy of 0.29 eV for the bipolaron dissociation. This finding leads to a
      hysteresis model that is generally valid for thin-film transistors with both band
      transport and hopping conduction in semiconducting thin films. 

PMID- 24463855
TI  - NSGC 2014 presidential address: just own it.

PMID- 24463854
TI  - Feasibility, safety and accuracy of regadenoson-atropine (REGAT) stress
      echocardiography for the diagnosis of coronary artery disease: an angiographic
      correlative study.
AB  - Regadenoson (REG), a selective A2A receptor vasodilator, has not been widely
      evaluated in stress echocardiography (SE). We report results of 45 patients
      participating in REG + atropine (REGAT) SE protocol conducted in a single-center
      prospective trial. The REGAT study enrolled subjects before a clinically
      indicated cardiac catheterization for suspected coronary artery disease (CAD).
      After rest imaging, a 2 mg Atropine (AT) bolus followed by 400 mcg of REG was
      given. Standard stress imaging views were obtained and interpreted in blinded
      fashion. Sensitivity, specificity, positive and negative predictive values (PPV,
      NPV) were calculated using cardiac catheterization >70 % stenosis as gold
      standard. Additional endpoints included major adverse cardiac events (MACE) and
      patient questionnaire responses. The mean duration of REGAT was 18 +/- 7.2 min.
      There were no MACE, with only transient side-effects of dry mouth, shortness of
      breath, and headache. The incidence of significant CAD was 51.1 %. The
      sensitivity and specificity for significant stenosis was 60.9 and 86.4 %, with a
      PPV and NPV of 82.4 and 67.9 %. By coronary territories, the sensitivity,
      specificity, PPV, and NPV were: left anterior descending artery 58.8, 92.9, 83.3,
      and 78.8 %; left circumflex artery 6.7, 93.3, 33.3, and 67.7 %; and right
      coronary artery 16.7, 93.9, 50, and 75.6 %. Over 90 % of subjects reported
      feeling comfortable, with 83 % preferring REGAT as a future stress modality. The
      REGAT protocol is fast, safe, and well-tolerated with good specificity for CAD
      detection, but its low sensitivity and NPV precludes it from being an imaging
      modality for routine use.

PMID- 24463856
TI  - Screening of alpha-glucosidase inhibitors from green tea extracts using
      immobilized enzymes affinity capture combined with UHPLC-QTOF MS analysis.
AB  - An applicable affinity capture-based method was developed for screening of enzyme
      inhibitors from complex plant extracts directly. By elimination of false
      positives, three non-competitive alpha-glucosidase inhibitors were fished out
      from 400 MUL green tea extract rapidly, using affinity capture of immobilized
      alpha-glucosidase combined with UHPLC-QTOF MS analysis. 

PMID- 24463857
TI  - Effects of storage time and temperature on coagulation tests and factors in fresh
      plasma.
AB  - Coagulation tests and factors measurements have been widely applied in clinical
      practice. Pre-analytical conditions are very important in laboratory
      assessment.Here,we aim to determine the effects of storage time and temperature
      on activated partial thromboplastin time (APTT), fibrinogen (Fbg), prothrombin
      time (PT), the international normalized ratio (INR), thrombin time (TT), factor
      VIII activity (FVIII:C), and factor IX activity (FIX:C) in fresh plasma. Seventy
      two blood samples were tested after storage for 0 (baseline), 2, 4, 6, 8, 12, and
      24 h at 25 degrees C (room temperature) and 4 degrees C (refrigeration) in two
      centers. The mean percentage change of greater than 10% and the numbers of
      samples with greater than 10% percentage changes more than 25% were used to
      determine clinically relevant difference. We demonstrated that samples for Fbg,
      PT/INR, and TT could be safely stored for <=24 h; FVIII:C for <=2 h; FIX:C for
      <=4 h both at 4 degrees C and 25 degrees C; and APTT for <=12 h at 4 degrees C
      and <=8 h at 25 degrees C.

PMID- 24463858
TI  - Combination therapy of 15-epi-lipoxin A4 with antibiotics protects mice from
      Escherichia coli-induced sepsis*.
AB  - OBJECTIVES: Inflammation occurs along with infection during sepsis. 15-Epi
      lipoxin A4 has protective and resolving effects in experimental models of
      infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined
      with antibiotics on Escherichia coli-induced peritonitis. DESIGN: Prospective
      experimental study. SETTING: University research laboratory. SUBJECTS: Male
      C57BL/6 mice. INTERVENTIONS: Mice were injected with E. coli to induce
      peritonitis and were given either 15-epi-lipoxin A4 (1 MUg/mouse) or placebo
      (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on
      peritoneal cell populations, bacterial burden, and cytokine production were
      assessed. Survival rates were observed for up to 7 days. In addition, we examined
      the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with
      lipopolysaccharide, CpG DNA, or live E. coli. MEASUREMENTS AND MAIN RESULTS:
      Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils
      in the peritoneum, inhibited production of cytokines and chemokines, and
      decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4
      with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi
      lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis
      factor-alpha by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages.
      Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced
      the production of interleukin-6 and tumor necrosis factor-alpha by peritoneal
      macrophages stimulated with live E. coli. CONCLUSIONS: 15-Epi-lipoxin A4 combined
      with antibiotics attenuated systemic inflammation, inhibited bacteria
      dissemination, and improved survival in E. coli-infected mice. The reduced
      production of interleukin-6 and tumor necrosis factor-alpha by peritoneal
      macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory
      response. Taken together, these data suggested that 15-epi-lipoxin A4 combined
      with antibiotics was beneficial in regulating the proinflammatory response in
      sepsis without exacerbating infection.

PMID- 24463859
TI  - Early multimodal outcome prediction after cardiac arrest in patients treated with
      hypothermia.
AB  - OBJECTIVES: Therapeutic hypothermia and pharmacological sedation may influence
      outcome prediction after cardiac arrest. The use of a multimodal approach,
      including clinical examination, electroencephalography, somatosensory-evoked
      potentials, and serum neuron-specific enolase, is recommended; however, no study
      examined the comparative performance of these predictors or addressed their
      optimal combination. DESIGN: Prospective cohort study. SETTING: Adult ICU of an
      academic hospital. PATIENTS: One hundred thirty-four consecutive adults treated
      with therapeutic hypothermia after cardiac arrest. MEASUREMENTS AND MAIN RESULTS:
      Variables related to the cardiac arrest (cardiac rhythm, time to return of
      spontaneous circulation), clinical examination (brainstem reflexes and
      myoclonus), electroencephalography reactivity during therapeutic hypothermia,
      somatosensory-evoked potentials, and serum neuron-specific enolase. Models to
      predict clinical outcome at 3 months (assessed using the Cerebral Performance
      Categories: 5 = death; 3-5 = poor recovery) were evaluated using ordinal logistic
      regressions and receiving operator characteristic curves. Seventy-two patients
      (54%) had a poor outcome (of whom, 62 died), and 62 had a good outcome.
      Multivariable ordinal logistic regression identified absence of
      electroencephalography reactivity (p < 0.001), incomplete recovery of brainstem
      reflexes in normothermia (p = 0.013), and neuron-specific enolase higher than 33
      MUg/L (p = 0.029), but not somatosensory-evoked potentials, as independent
      predictors of poor outcome. The combination of clinical examination,
      electroencephalography reactivity, and neuron-specific enolase yielded the best
      predictive performance (receiving operator characteristic areas: 0.89 for
      mortality and 0.88 for poor outcome), with 100% positive predictive value.
      Addition of somatosensory-evoked potentials to this model did not improve
      prognostic accuracy. CONCLUSIONS: Combination of clinical examination,
      electroencephalography reactivity, and serum neuron-specific enolase offers the
      best outcome predictive performance for prognostication of early postanoxic coma,
      whereas somatosensory-evoked potentials do not add any complementary information.
      Although prognostication of poor outcome seems excellent, future studies are
      needed to further improve prediction of good prognosis, which still remains
      inaccurate.

PMID- 24463860
TI  - [Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. Its history].

PMID- 24463861
TI  - [Pharmacogenetics of tacrolimus: from bench to bedside?].
AB  - Tacrolimus (FK-506) is an immunosuppressant widely used to prevent kidney
      transplant rejection. Patients receive an initial standard dose and tacrolimus
      levels are measured in blood. If necessary, the dose is adjusted to reach a blood
      concentration within the accepted range. There is great interindividual
      variability in the dose required to achieve the target blood level, and many
      patients require multiple modifications of the dose to reach the range. One of
      the main determinants of these differences is a CYP3A5 gene polymorphism that
      determines that about 80% of Caucasians are poor metabolisers and require lower
      doses compared to the extensive metabolisers. It has been proposed that
      transplanted patients could receive an initial Tacrolimus dose based on the
      CYP3A5 genotype. This could reduce the time to achieve the optimal blood level,
      reducing the number of dose modifications. However, to be accepted by clinicians
      and translated to the clinical practice this adapted dose procedure should give
      additional advantages such as a significant reduction of the rates of
      nephrotoxicity and rejection, or a lower cost due to less dose modifications of
      Tacrolimus and less antibody induction therapy. 

PMID- 24463862
TI  - [Diagnostic value of soluble urokinase-type plasminogen activator receptor serum
      levels in adults with idiopathic nephrotic syndrome].
AB  - INTRODUCTION: Recent studies suggest that soluble urokinase-type plasminogen
      activator receptor (suPAR) levels could be useful for distinguishing idiopathic
      focal segmental glomerulosclerosis (FSGS) from other glomerulopathies that cause
      nephrotic syndrome, but these data have not been confirmed in independent
      studies. The objective of our study is to analyse whether circulating levels of
      suPAR are useful for identifying primary kidney disease in patients with
      nephrotic syndrome secondary to FSGS, minimal change disease or idiopathic
      membranous nephropathy (MN). METHODS: We measured circulating suPAR at diagnosis
      in 60 patients with nephrotic syndrome secondary to FSGS, minimal change disease
      (MCD) and membranous nephropathy (MN). The correlations between suPAR levels and
      demographic, clinical and biochemical variables were analysed. The sensitivity
      and specificity of suPAR in distinguishing FSGS patients were analysed by ROC
      curves. RESULTS: After adjusting for age and renal function, suPAR levels were
      significantly higher in patients with FSGS than in those with MCD (p<.001), but
      there were no differences between FSGS and MN (P=.12). A suPAR value >=3452 pg/ml
      had a sensitivity of 73.7% and a specificity of 72.5%, with an area under the
      curve (AUC) of 0.782 +/- 0.124, p=.001, for identifying patients with FSGS. After
      excluding patients with MN, a value >=3531 pg/ml had a specificity of 99.93% for
      distinguishing between MCD and FSGS. CONCLUSIONS: suPAR values alone do not
      distinguish between the three types of glomerulopathy. Nevertheless, after
      excluding the diagnosis of MN, a suPAR level >3531 pg/ml could have a high
      specificity (but a low sensitivity) in the diagnosis of FSGS.

PMID- 24463863
TI  - [Value of soluble urokinase receptor serum levels in the differential diagnosis
      between idiopathic and secondary focal segmental glomerulosclerosis].
AB  - BACKGROUND: It has been reported that the circulating level of the soluble
      urokinase receptor (suPAR) could be useful for distinguishing idiopathic from
      secondary focal segmental glomerulosclerosis, but the results published are
      conflicting. In this study, we analyse the intraindividual variability and
      clinical and anatomopathological variables associated with the suPAR levels and
      if circulating suPAR levels allow the different forms of focal segmental
      glomerulosclerosis (FSGS) to be distinguished, i.e., idiopathic forms from
      secondary FSGS, regardless of the presence of nephrotic syndrome and the activity
      phase. METHOD: We studied 35 patients affected by idiopathic FSGS and 48 with
      secondary FSGS (83 in total). We carried out measurements of circulating suPAR at
      the time of diagnosis and/or after remission and we analysed correlations between
      suPAR levels and demographic, clinical and biochemical variables. The ability of
      suPAR to distinguish between both forms of FSGS was analysed by ROC curves and
      logistic regression analysis. RESULTS: In both forms of FSGS, suPAR levels were
      independent of proteinuria and the histopathological subtype of FSGS and they
      were significantly associated with age and renal function. After adjusting for
      both variables, suPAR levels were significantly higher in patients with
      idiopathic FSGS, both in the nephrotic syndrome phase and in partial or complete
      remission. The most sensitive suPAR level (80%) and the most specific (73%) for
      discriminating between idiopathic and secondary forms was 3443.6 pg/ml (area
      below curve [ABC] 0.78 +/- 0.083, P<.001). In the logistic regression analysis,
      after adjusting for age, renal function and presence of nephrotic syndrome, suPAR
      levels were independently associated with the diagnosis of idiopathic FSGS, but
      the model was poorly adjusted for low risk categories in which it tended to
      classify primary forms as secondary forms (chi(2) = 11.2 p=.027). CONCLUSIONS:
      SuPAR levels lack sensitivity for differentiating between idiopathic and
      secondary FSGS. However, suPAR values greater than 4000 ng/ml are highly specific
      to primary FSGS, and as such, with a morphological FSGS pattern associated with
      non-nephrotic proteinuria, they would indicate a low probability of secondary
      FSGS.

PMID- 24463865
TI  - [Metabolic syndrome is associated with cardiovascular events in haemodialysis].
AB  - BACKGROUND: Metabolic syndrome (MS) is a cardiovascular risk factor and is
      associated with mortality in the general population and in patients with chronic
      kidney disease. However, few studies have been carried out in patients on
      haemodialysis (HD). OBJECTIVES: The objective of the study is to analyse the
      effect of MS on the occurrence of cardiovascular events in HD. The secondary
      objective is to determine the influence of the fat tissue index and conicity
      index on cardiovascular events. METHODS: A prospective study including 100
      patients on HD. The follow-up period was 3 years. Cardiovascular events and
      mortality were recorded. MS was defined in accordance with ATPIII and IDF
      criteria. RESULTS: MS prevalence as defined by the ATPIII was 32%, and by the
      IDF, 29%. The concordance between the two definitions was high (kappa index 0.79,
      95% confidence interval 0.65 to 0.92). The risk of cardiovascular events was
      higher in patients with MS (Log Rank 6.185, p = 0.013), with a fat tissue index
      greater than 11.5 kg/m(2) (log rank 10.220, p=.001) and a conicity index greater
      than 1.2 (log rank 6.393, p=.011). In the Cox analysis, adjusted for age and sex,
      patients with MS had twice the risk of being admitted due to a cardiovascular
      event (odds ratio 1.93, 1.022 to 3.6, p=.043). Mortality was 35% in the 3 year
      follow-up period with no differences between the groups with and without MS.
      CONCLUSIONS: MS is a very prevalent disease in HD patients and its presence
      doubles the risk of hospitalisation due to cardiovascular events in the short
      term.

PMID- 24463864
TI  - [Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism
      after kidney transplantation: one-year follow-up multicentre study].
AB  - BACKGROUND: The effect of cinacalcet in patients with persistent secondary
      hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been
      reported in patients with secondary hypercalcaemia. OBJECTIVES: Our objective was
      to assess the long-term effect of cinacalcet on patients with a RT and
      normocalcaemic SHPT. METHODS: A one-year multicentre, observational,
      retrospective study that included kidney recipients with SHPT (intact parathyroid
      hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2
      mg/dl). Patients began treatment with cinacalcet in clinical practice. RESULTS:
      32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male,
      were included in the study. Treatment with cinacalcet began a median of 16 months
      after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25,
      P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6
      months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2%
      reduction, P=.001), without there being changes in calcium and phosphorus levels
      (P=.214 and P=.216, respectively). No changes were observed in kidney function or
      anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to
      intolerance and 6.2% due to a lack of efficacy. CONCLUSIONS: In patients with
      normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values
      without causing changes to calcaemia, phosphataemia or kidney function.
      Cinacalcet showed good tolerability.

PMID- 24463866
TI  - [Early kidney transplant failure and return to peritoneal dialysis: preliminary
      study of permeability and dialysis efficacy].
AB  - The return to dialysis after kidney transplant (TX) failure is increasingly
      common. On returning to dialysis after TX failure, there is usually a similar or
      worse clinical situation than in patients who are on haemodialysis or peritoneal
      dialysis (PD) for the first time. Although there are several studies on the
      clinical situation of patients who return to PD after long periods with a
      functioning TX, there is hardly any information on the progression of a patient
      subgroup returning to PD after TX failure a few days or weeks after
      transplantation. OBJECTIVE: Assess whether a short period of time on suboptimal
      TX and aggressive treatment/measures may influence membrane permeability, the
      clinical situation and dialysis efficacy on returning to PD. PATIENTS AND METHOD:
      In 9 patients (53.5 +/- 15.4 years of age, 5 males and 4 females) who had
      previously been on PD before early TX failure and had returned to PD (25 +/- 23
      days, range 10-64) over the last five years, we studied laboratory data including
      inflammation, nutrition, kidney function, permeability and PD efficacy, at four
      points during progression: before TX, immediately after returning to PD and after
      one month and three months on PD. RESULTS: We did not detect significant
      differences in the progression of nutrition and inflammation parameters. Diuresis
      decreased significantly from pre-TX volume to diuresis on return to PD and after
      one month on PD (p=.032), remaining at low levels after three months on PD. UF
      decreased from 1407 to 951 ml/day (p=.022) and from 314 to 260 ml/4h (p=.018) in
      the peritoneal equilibration test after three months on PD, without changes being
      observed in the creatinine dialysate/plasma ratio. Kt/V and weekly creatinine
      clearance decreased slightly and remained at adequate efficacy levels.
      CONCLUSIONS: In this small sample of patients, who returned to PD after early TX
      failure, it does not appear that the measures involved in managing a graft at
      risk over a short period of time have a major effect on clinical parameters and
      permeability or peritoneal efficacy.

PMID- 24463867
TI  - [Persistent microhaematuria with negative or low proteinuria].
AB  - The level of proteinuria continues to be the clinical parameter that is best
      related to the development of long-term renal failure in glomerular pathologies.
      This quantity is particularly important when we analyse the progression of
      patients with IgA nephropathy. As such, the natural progression of patients with
      IgA who clinically present with normal kidney function, microhaematuria and low
      proteinuria had not been analysed comprehensively until the Spanish multicentre
      study herein analysed. After studying 141 Caucasian patients with biopsied IgA
      nephropathy and a "benign" clinical profile and after they were classified
      histologically in accordance with the new Oxford classification, it could be
      concluded that the renal prognosis of these patients was excellent. This is the
      first study in the literature that demonstrates the usefulness of this new
      classification in patients who clinically have normal renal function and
      proteinuria below 0.5 g/day. The latest advances in the genetics of this disease,
      as well as in the collaboration of complement pathways in its pathophysiology
      mean that these results cannot be extrapolated to all the populations studied. In
      addition, the analysis and follow-up of microhaematuria has regained importance
      as an independent prognostic factor for developing renal failure, although there
      are no consistent studies in this regard yet. However, it is a subject that
      should be examined again by the nephrology community.

PMID- 24463868
TI  - [Complications associated with renal graft biopsy in transplant patients].
AB  - BACKGROUND: Percutaneous biopsy of renal grafts is a diagnostic method for the
      assessment, management and clinical monitoring of renal transplant, so it is
      necessary to know its complications. There are few data in the literature
      regarding complications from biopsies in renal grafts. OBJECTIVE: To evaluate the
      rate of complications in renal graft biopsies performed at our centre. PATIENTS
      AND METHOD: We performed a retrospective observational study, including data from
      patients who underwent renal graft biopsies from January 2000 to September 2012.
      Major complications were defined as: anemia requiring blood transfusion,
      intraparenchymal arteriovenous fistula or arterial bleeding requiring
      embolisation, nephrectomy, other surgery and exitus. And as minor complications:
      anemia without blood transfusion, intraparenchymal arteriovenous fistula without
      embolisation, haematomas or perirenal collections, hematuria and fever. Kidney
      biopsies were performed with ultrasound guidance and automatic devices. RESULTS:
      We performed 390 kidney graft biopsies. 49 complications occurred. 22 were major:
      12 per anemia that required blood transfusion, 6 requiring embolisation (5
      arteriovenous fistulae and 1 arterial bleeding), 2 exitus, 1 trasplantectomy and
      1 surgery (haematoma). 27 were minor: 12 perirenal collections, 9 arteriovenous
      fistulae without embolisation, 3 hematuria, 2 anemisation without blood
      transfusion and 1 fever. CONCLUSIONS: The rate of complications related to renal
      graft biopsy observed in our centre is similar to those described for native
      kidneys, therefore we believe it remains a safe and effective technique, and an
      important diagnostic tool.

PMID- 24463869
TI  - [Successful treatment of rhino-orbital-cerebral mucormycosis in a kidney
      transplant patient].
AB  - Rhino-orbital-cerebral mucormycosis is a potentially fatal mycotic infection in
      immunosuppressed patients. The main risk factors for acquiring this infection are
      poorly controlled diabetes mellitus, iron overload, potent immunosuppression and
      chronic steroid use. In this review, we present the case of a kidney transplant
      patient who, after treatment of an acute rejection episode with high doses of
      steroids and potent immunosuppression with tacrolimus and mycophenolate,
      presented with rapidly progressing rhino-orbital-cerebral mucormycosis that
      required aggressive surgical treatment, immunosuppression discontinuation and
      potent antifungal treatment.

PMID- 24463870
TI  - Comment on "IgM nephropathy in children: clinicopathological analysis".

PMID- 24463871
TI  - [Prevalence of chronic kidney disease in patients infected by the human
      immunodeficiency virus].

PMID- 24463872
TI  - Response to the comment on "IgM nephropathy in children: clinicopathologic
      analysis".

PMID- 24463873
TI  - [Cloudy peritoneal effluent and diarrhoea due to Clostridium difficile].

PMID- 24463874
TI  - [Acquired perforating dermatosis in patients with chronic renal failure. A report
      of two cases and a review of the literature].

PMID- 24463875
TI  - [Treatment of infection due to hepatitis C virus in haemodialysis].

PMID- 24463876
TI  - [Hypocalcaemia, hyperphosphataemia and elevated parathyroid hormone, a difficult
      differential diagnosis?].

PMID- 24463877
TI  - [Spontaneous fistulae in the arms: a case study].

PMID- 24463878
TI  - Dermatomyositis in a kidney transplant patient: a case report.

PMID- 24463879
TI  - [Results of the cooperative study of Spanish peritoneal dialysis registries:
      analysis of 12 years of follow-up].
AB  - INTRODUCTION AND OBJECTIVES: There is currently no registry that gives a complete
      and overall view of the peritoneal dialysis (PD) situation in Spain. However, a
      report on PD in Spain was developed for various conferences and meetings over
      several years from data provided by each registry in the autonomous communities
      and regions. The main objective of this study is to analyse this data in
      aggregate and comparatively to obtain a representative sample of the Spanish
      population on PD in recent years, in order that analysis and results in terms of
      demographic data, penetration of the technique, geographical differences,
      incidence and prevalence, technical aspects, intermediate indicators,
      comorbidity, and outcomes such as patient and technique survival may be
      extrapolated to the whole country. DESIGN, MATERIAL AND METHOD: Observational
      cohort study of autonomous PD registries, covering the largest possible
      percentage of the adult Spanish population (over 14 years of age) on PD, at least
      in the last decade (1999-2010), and in the largest possible geographical area in
      which we were able to recruit. A precise data collection strategy was followed
      for each regional registry. Once the information was received and clarified, they
      were added as aggregate data for statistical study. RESULTS: The regional
      registries that participated represent a total geographical area that encompasses
      32,853,251 inhabitants over 14 years of age, 84% of the total Spanish population
      older than that age. The mean annual rate of incidents per million inhabitants
      (ppm) was variable (between 17.81 ppm in Andalusia and 29.90 ppm in the Basque
      Country), with a discrete and permanent increase in the overall PD incidence in
      Spain being observed in recent years. The mean annual prevalence per million
      population (ppm) was very heterogeneous (from 42 to 99 ppm). A mean progressive
      increase in the use of automated peritoneal dialysis (APD) was observed. The
      peritonitis rate was approximately one episode every 25-30 months/patient, with a
      slight decrease being observed in recent years. The causes of discontinuing PD
      were distributed fairly evenly between communities; almost a third was due to
      patient death (mean 28%), a third was due to renal transplantation (mean 39%) and
      a third was due to transfer to haemodialysis (technique failure: mean 32%). The
      main comorbidities were cardiovascular disease (30.2%) and diabetes mellitus
      (24.2%). The overall accumulated mean survival was 92.2%, 82.8%, 74.2%, 64.8% and
      57% after one, two, three, four and five years respectively. There was
      significantly and independently worse survival for older patients and those with
      cardiovascular disease, patients with diabetes mellitus, those on continuous
      ambulatory peritoneal dialysis (vs. APD), those who started PD before 2004
      (analysed in Andalusia and Catalonia), and patients with lower residual renal
      function at the start of PD (analysed in the Levante registry). Similarly, the
      technique survival has improved, showing a mean figure above 50% after 5 years.
      CONCLUSIONS: The incidence and prevalence of PD in Spain are growing moderately
      and in a generalised manner and continue to maintain an irregular distribution by
      autonomous community. Both patient and technique survival were greater than 50%
      after 5 years, with an improvement being observed in recent years, and are
      comparable to countries with better results in this treatment.

PMID- 24463880
TI  - Relationship of acetabular dysplasia in females with osteoarthritis of the hip to
      the distance between both anterior superior iliac spines.
AB  - BACKGROUND: Acetabular dysplasia (AD) is the main cause of hip osteoarthritis in
      Japan. A simple method to evaluate acetabular dysplasia would be helpful for
      early treatment or prevention of hip osteoarthritis. Acetabular dysplasia is
      reported to be associated with pathological transverse growth of the pelvis,
      indicating that the distance between the 2 anterior superior iliac spines might
      be useful for screening and detection of acetabular dysplasia. The purpose of
      this study was to determine if the acetabular dysplasia radiographic parameters
      are related to the distance between the 2 anterior superior iliac spines in
      patients with hip osteoarthritis. MATERIAL AND METHODS: In this study, data
      obtained in a previous multi-institutional examination of patients with hip
      osteoarthritis in Japan were evaluated. The anterior superior iliac spine
      distances of 176 female patients (mean age, 54 years; range, 18-85 years) were
      measured by physical examination. The relationship between the anterior superior
      iliac spine distance and acetabular dysplasia was analyzed, and the anterior
      superior iliac spine distances of the patients with acetabular dysplasia who were
      at relatively high risk for hip osteoarthritis were compared with that of the
      patients at lower risk. RESULTS: A statistically significant relationship between
      the anterior superior iliac spine distance and all of the acetabular dysplasia
      parameters was observed. The anterior superior iliac spine distances of the
      acetabular dysplasia patients with a relatively high risk for radiographic
      acetabular dysplasia parameters were significantly smaller than those of patients
      at lower risk. Even after adjustment for age, height, and weight, significantly
      increased relative risk for having high risk AD was found in patients with an
      ASIS distance of less than 24.5 cm. CONCLUSIONS: There was a significant
      relationship between the anterior superior iliac spine distance and the degree of
      acetabular dysplasia.

PMID- 24463881
TI  - The presence of CD55- and/or CD59-deficient erythrocytic populations in patients
      with rheumatic diseases reflects an immune-mediated bone-marrow derived
      phenomenon.
AB  - BACKGROUND: Complement has the potential to provoke severe impairment to host
      tissues, as shown in autoimmune diseases where complement activation has been
      associated with diminished CD55 and/or CD59 expression on peripheral blood cell
      membranes. The aim of this study was to evaluate the presence of CD55- and/or
      CD59-deficient erythrocytic populations in patients with different rheumatic
      diseases and to investigate possible correlations with clinical or laboratory
      parameters. MATERIAL AND METHODS: CD55 and CD59 expression was evaluated in
      erythrocytes of 113 patients with rheumatic diseases, 121 normal individuals, and
      10 patients with paroxysmal nocturnal hemoglobinuria (PNH) using the Sephacryl
      gel microtyping system. Ham and sucrose tests were also performed. RESULTS:
      Interestingly, the majority of patients (104/113, 92%) demonstrated CD55- and/or
      CD59-deficient erythrocytes: 47 (41.6%) with concomitant deficiency of CD55 and
      CD59, 50 (44.2%) with isolated deficiency of CD55, and 6 (6.2%) with isolated
      deficiency of CD59. In normal individuals, only 2 (1%) had concomitant CD55/CD59
      negativity and 3 (2%) had isolated CD55 or CD59 deficiency. All PNH patients
      exhibited simultaneous CD55/CD59 deficiency. Positive Ham and sucrose tests were
      found only in PNH patients. There was no association between the CD55- and/or
      CD59-deficient erythrocytes and hemocytopenias or undergoing treatment. However,
      CD55 expression significantly influenced hemoglobin values (F=6.092, p=0.015).
      CONCLUSIONS: This study provides evidence supporting the presence of erythrocytes
      with CD55 and/or CD59 deficiency in patients with rheumatic diseases. Moreover,
      CD55 deficiency on red cells influences hemoglobin concentration. Further studies
      using molecular techniques will clarify the exact pathophysiological mechanisms
      of this deficiency.

PMID- 24463882
TI  - Partial restoration of cardiac function with DeltaPDZ nNOS in aged mdx model of
      Duchenne cardiomyopathy.
AB  - Transgenic gene deletion/over-expression studies have established the
      cardioprotective role of neuronal nitric oxide synthase (nNOS). However, it
      remains unclear whether nNOS-mediated heart protection can be translated to gene
      therapy. In this study, we generated an adeno-associated virus (AAV) nNOS vector
      and tested its therapeutic efficacy in the aged mdx model of Duchenne
      cardiomyopathy. A PDZ domain-deleted nNOS gene (DeltaPDZ nNOS) was packaged into
      tyrosine mutant AAV-9 and delivered to the heart of ~14-month-old female mdx
      mice, a phenotypic model of Duchenne cardiomyopathy. Seven months later, we
      observed robust nNOS expression in the myocardium. Supra-physiological DeltaPDZ
      nNOS expression significantly reduced myocardial fibrosis, inflammation and
      apoptosis. Importantly, electrocardiography and left ventricular hemodynamics
      were significantly improved in treated mice. Additional studies revealed
      increased phosphorylation of phospholamban and p70S6K. Collectively, we have
      demonstrated the therapeutic efficacy of the AAV DeltaPDZ nNOS vector in a
      symptomatic Duchenne cardiomyopathy model. Our results suggest that the
      cardioprotective role of DeltaPDZ nNOS is likely through reduced apoptosis,
      enhanced phospholamban phosphorylation and improved Akt/mTOR/p70S6K signaling.
      Our study has opened the door to treat Duchenne cardiomyopathy with DeltaPDZ nNOS
      gene transfer.

PMID- 24463883
TI  - Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes
      and improves molecular diagnosis.
AB  - In severe early-onset epilepsy, precise clinical and molecular genetic diagnosis
      is complex, as many metabolic and electro-physiological processes have been
      implicated in disease causation. The clinical phenotypes share many features such
      as complex seizure types and developmental delay. Molecular diagnosis has
      historically been confined to sequential testing of candidate genes known to be
      associated with specific sub-phenotypes, but the diagnostic yield of this
      approach can be low. We conducted whole-genome sequencing (WGS) on six patients
      with severe early-onset epilepsy who had previously been refractory to molecular
      diagnosis, and their parents. Four of these patients had a clinical diagnosis of
      Ohtahara Syndrome (OS) and two patients had severe non-syndromic early-onset
      epilepsy (NSEOE). In two OS cases, we found de novo non-synonymous mutations in
      the genes KCNQ2 and SCN2A. In a third OS case, WGS revealed paternal isodisomy
      for chromosome 9, leading to identification of the causal homozygous missense
      variant in KCNT1, which produced a substantial increase in potassium channel
      current. The fourth OS patient had a recessive mutation in PIGQ that led to exon
      skipping and defective glycophosphatidyl inositol biosynthesis. The two patients
      with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1,
      respectively. Mutations in these genes were not found among 500 additional
      individuals with epilepsy. This work reveals two novel genes for OS, KCNT1 and
      PIGQ. It also uncovers unexpected genetic mechanisms and emphasizes the power of
      WGS as a clinical tool for making molecular diagnoses, particularly for highly
      heterogeneous disorders.

PMID- 24463885
TI  - The performance of different propensity score methods for estimating absolute
      effects of treatments on survival outcomes: A simulation study.
AB  - Observational studies are increasingly being used to estimate the effect of
      treatments, interventions and exposures on outcomes that can occur over time.
      Historically, the hazard ratio, which is a relative measure of effect, has been
      reported. However, medical decision making is best informed when both relative
      and absolute measures of effect are reported. When outcomes are time-to-event in
      nature, the effect of treatment can also be quantified as the change in mean or
      median survival time due to treatment and the absolute reduction in the
      probability of the occurrence of an event within a specified duration of follow
      up. We describe how three different propensity score methods, propensity score
      matching, stratification on the propensity score and inverse probability of
      treatment weighting using the propensity score, can be used to estimate absolute
      measures of treatment effect on survival outcomes. These methods are all based on
      estimating marginal survival functions under treatment and lack of treatment. We
      then conducted an extensive series of Monte Carlo simulations to compare the
      relative performance of these methods for estimating the absolute effects of
      treatment on survival outcomes. We found that stratification on the propensity
      score resulted in the greatest bias. Caliper matching on the propensity score and
      a method based on earlier work by Cole and Hernan tended to have the best
      performance for estimating absolute effects of treatment on survival outcomes.
      When the prevalence of treatment was less extreme, then inverse probability of
      treatment weighting-based methods tended to perform better than matching-based
      methods.

PMID- 24463884
TI  - Insights into the mechanisms of macular degeneration associated with the R172W
      mutation in RDS.
AB  - Mutations in the photoreceptor tetraspanin gene peripherin-2/retinal degeneration
      slow (PRPH2/RDS) cause both rod- and cone-dominant diseases. While rod-dominant
      diseases, such as autosomal dominant retinitis pigmentosa, are thought to arise
      due to haploinsufficiency caused by loss-of-function mutations, the mechanisms
      underlying PRPH2-associated cone-dominant diseases are unclear. Here we took
      advantage of a transgenic mouse line expressing an RDS mutant (R172W) known to
      cause macular degeneration (MD) in humans. To facilitate the study of cones in
      the heavily rod-dominant mouse retina, R172W mice were bred onto an Nrl(-/-)
      background (in which developing rods adopt a cone-like fate). In this model the
      R172W protein and the key RDS-binding partner, rod outer segment (OS) membrane
      protein 1 (ROM-1), were properly expressed and trafficked to cone OSs. However,
      the expression of R172W led to dominant defects in cone structure and function
      with equal effects on S- and M-cones. Furthermore, the expression of R172W in
      cones induced subtle alterations in RDS/ROM-1 complex assembly, specifically
      resulting in the formation of abnormal, large molecular weight ROM-1 complexes.
      Fundus imaging demonstrated that R172W mice developed severe clinical signs of
      disease nearly identical to those seen in human MD patients, including retinal
      degeneration, retinal pigment epithlium (RPE) defects and loss of the
      choriocapillaris. Collectively, these data identify a primary disease-causing
      molecular defect in cone cells and suggest that RDS-associated disease in
      patients may be a result of this defect coupled with secondary sequellae
      involving RPE and choriocapillaris cell loss.

PMID- 24463886
TI  - Can we believe the DAGs? A comment on the relationship between causal DAGs and
      mechanisms.
AB  - Directed acyclic graphs (DAGs) play a large role in the modern approach to causal
      inference. DAGs describe the relationship between measurements taken at various
      discrete times including the effect of interventions. The causal mechanisms, on
      the other hand, would naturally be assumed to be a continuous process operating
      over time in a cause-effect fashion. How does such immediate causation, that is
      causation occurring over very short time intervals, relate to DAGs constructed
      from discrete observations? We introduce a time-continuous model and simulate
      discrete observations in order to judge the relationship between the DAG and the
      immediate causal model. We find that there is no clear relationship; indeed the
      Bayesian network described by the DAG may not relate to the causal model.
      Typically, discrete observations of a process will obscure the conditional
      dependencies that are represented in the underlying mechanistic model of the
      process. It is therefore doubtful whether DAGs are always suited to describe
      causal relationships unless time is explicitly considered in the model. We relate
      the issues to mechanistic modeling by using the concept of local (in)dependence.
      An example using data from the Swiss HIV Cohort Study is presented.

PMID- 24463887
TI  - Comparison of treatments in a cataract surgery with circular response.
AB  - Circular data are a natural outcome in many biomedical studies, e.g. some
      measurements in ophthalmologic studies, degrees of rotation of hand or waist,
      etc. With reference to a real data set on astigmatism induced in two types of
      cataract surgeries we carry out some two-sample testing problems with the
      possibility of common or different concentration parameters in the circular set
      up. Detailed simulation study and the analysis of the data set, including
      redesigning the cataract surgery data, are carried out.

PMID- 24463889
TI  - [The new phase of bariatric surgery in Brazil].

PMID- 24463888
TI  - Antidepressant-like effect of celecoxib piroxicam in rat models of depression.
AB  - Beyond the current hypothesis of depression, several new biological substrates
      have been proposed for this disorder. The present study investigated whether the
      anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in
      animal models of depression. After acute administration, we observed
      antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in
      the modified forced swim test in rats. Piroxicam increased serotonin and
      norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with
      celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a
      chronic mild stress model of depression. Additionally, the chronic mild stress
      induced reduction of hippocampal glutathione was prevented by treatment with
      celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased
      after chronic mild stress compared with the non-stressed saline group. The non
      stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an
      increase in hippocampal superoxide dismutase activity compared with the stressed
      saline group. Lipid hydroperoxide was increased in the stressed group treated
      with vehicle and non-stressed group treated with imipramine but not in the
      stressed groups treated with celecoxib and piroxicam. These results suggest that
      the antidepressant-like effects of anti-inflammatory drugs might be attributable
      to enhanced antioxidant defenses and attenuated oxidative stress in the
      hippocampus. 

PMID- 24463890
TI  - Early outcomes of the first Brazilian experience in totally robotic bariatric
      surgery.
AB  - BACKGROUND: Currently, bariatric surgery is the most effective therapy for morbid
      obesity, and the laparoscopic approach is considered gold-standard for Roux-en-Y
      gastric bypass. Totally robotic Roux-en-Y gastric bypass has been proposed as a
      major evolution in minimally invasive bariatric surgery and its use is becoming
      more widespread. AIM: To provide an early report of the first Brazilian case
      series of totally robotic gastric bypass and perioperative short-term outcomes.
      METHODS: All consecutive patients who underwent totally robotic gastric bypass at
      two recognized centers of bariatric surgery were included. Patient demographic
      data, body mass index, operative times, hospital stay, complications and
      mortality in the 30 postoperative days were recorded. The surgeons received the
      same training program before the clinical procedures and all the surgeries were
      performed under the supervision of an experienced robotic surgeon. RESULTS: The
      surgeries were performed by five surgeons and included 68 patients (52 women -
      76.5%), with a mean age of 40.5 years (range 18 to 59) and mean BMI of 41.3 (35.2
      - 59.2). Total mean operative time was 158 minutes (range 90 to 230) and mean
      overall hospital stay was 48 h. Postoperative surgical complication rate (30 day)
      was 5.9%, with three minor and one major complication. There was no mortality,
      leak or stricture. CONCLUSION: Even with surgeons in early learning curves, the
      robotic approach within a well-structured training model was safe and
      reproducible for the surgical treatment of the morbid obesity.

PMID- 24463891
TI  - Comparison of ghrelin plasma levels between pre and postoperative period in
      patients submitted to gastric plication associated with fundoplication.
AB  - BACKGROUND: The recurrence of the gastroesophageal reflux disease may be related
      to later postoperative weight gain, therefore increasing the chances of
      developing columnar metaplasia and cancer. The gastric plication associated with
      fundoplication can be employed in order to be treating the two issues. AIM: To
      evaluate the serum ghrelin hormone in pre and postoperatively as well as weight
      loss and control of reflux disease in patients undergoing gastroplication
      associated with fundoplication. METHODS: Was performed laparoscopic gastric
      plication with fundoplication in eight patients; endoscopic examinations were
      performed pre and postoperatively as well as blood collection for ghrelin
      hormonal dosage. RESULTS: There was control of reflux symptoms and mucosal
      lesions. Weight loss was significant. Since the change of the hormone ghrelin was
      not of great significance. CONCLUSIONS: Gastric plication associated with
      fundoplication was effective in treating reflux disease with surgical indication
      and for weight loss in obese patients. Appetite control occurs, but not due to
      ghrelin, because no significant decrease of its plasmatic levels was observed.

PMID- 24463892
TI  - Long follow-up of patients with gastric band.
AB  - BACKGROUND: The adjustable gastric band laparoscopic technique is safe,
      reversible and potentially effective alternative to gastric bypass Y-deRoux.
      However, it has a high rate of reoperation and unsatisfactory weight loss.
      OBJECTIVE: To present a cases series with the use of gastric banding in long term
      follow-up analyzing the withdrawal rate, its causes and the surgical conversions
      performed METHODS: Retrospective study based on the analysis of 19 patients who
      underwent the procedure between November 1999 and November 2002, and reviewed
      with clinical follow-up until late February 2011. The patients were analyzed in
      the following aspects: gender, age, preoperative weight, preoperative BMI,
      duration of follow-up, reasons for removal of the gastric band, need for
      conversion to another type of surgery and failure rate of surgical method.
      RESULTS: Nineteen patients underwent the procedure, four women and 15 men. The
      mean preoperative BMI was 41.95 kg/m2 (36-54). The band was withdrawn in 13
      patients (68.42%), including seven by erosion, four for unsatisfactory weight
      loss and two for gastroesophageal reflux. The gastric bypass was conducted in ten
      patients and Scopinaro operation in one. Two patients had not been reoperated
      till nowadays and four were lost in late follow-up. CONCLUSION: The gastric band
      is technically unsatisfactory in long-term evaluation, have high withdrawal rate
      due to migration or unsatisfactory weight loss.

PMID- 24463893
TI  - Obesity induction with high fat sucrose in rats.
AB  - BACKGROUND: Although is complex to identify the factors responsible for the
      important growth in obesity all over the world, the main causes are increased
      consumption of energy, highly saturated fats and sugars, and reduced physical
      activity. AIM: To compare rats with normal and supplemented diet with sucrose in
      relationship to body mass, weight of gonadal and retroperitoneal fat and Lee
      index. METHODS: Forty rats were divided into two groups: 20 in the control group
      that received normal chow diet and water for three months, and 20 animals in the
      experimental group who received the same diet but supplemented with sucrose 300
      g/l of water. The animals were weighed once a week during 91 days. At scheduled
      death, they had measured the naso-anal length, body weight and Lee index. After
      laparotomy, retroperitoneal and gonadal fat were isolated, dried and the
      percentage of weight in relation to body weight at the date of death was
      evaluated. RESULTS: There was a statistic significant difference between the 14th
      and 78th day favoring the experiment group indicating that sucrose interferes
      with weight gain in rats. The average weight was higher in the experimental group
      in all periods in comparison to initial weight. There was also significant
      difference in the weight of the gonadal and retroperitoneal fat. There was no
      significant difference comparing the Lee index. CONCLUSION: The body mass index
      was higher in animals treated with diet supplemented with sucrose and had higher
      gonadal and retroperitoneal fat, but no difference in the Lee index.

PMID- 24463894
TI  - Esophageal motility after gastric bypass in Roux-en-Y for morbid obesity: high
      resolution manometry findings.
AB  - BACKGROUND: Bariatric operations may alter esophageal motility; however, there is
      a paucity of studies of the esophageal motility with high resolution manometry.
      AIM: To study patients after Roux-en-Y gastric bypass for morbid obesity with
      high resolution motility. METHODS: Were included 18 asymptomatic patients (17
      women, mean age 53 years) after undergoing to Roux-en-Y gastric bypass for morbid
      obesity. All patients underwent high resolution motility after a mean follow-up
      of three years after the operation. RESULTS: The mean pressure of the lower
      esophageal sphincter was 18 +/- 13 (range 0-51) mmHg. Seven (39%) patients had a
      hypotonic sphincter and one (5%) hypertonicity. Sphincter relaxation was abnormal
      in one patient. Total and abdominal lower esophageal sphincter length was 4 +/- 1
      (1-7) cm e 2 +/- 1 (0-3) cm, respectively. Esophageal body distal amplitude
      (average measurements at 3 and 7 cm above the lower esophageal sphincter) was 77
      +/- 22 (40-120) mmHg. One (5%) patient had hypocontractility. Peristaltic waves
      were found in 95 +/- 0% (60-100). The upper esophageal sphincter basal pressure
      was 118 +/- 82 (33 - 334) mmHg; one (5%) patient (5%) had a hypotonic upper
      sphincter and eight (44%) hypertonicity. CONCLUSION: After gastric bypass in Roux
      en-Y occurs significant lower esophageal sphincter hypotonia and upper esophageal
      sphincter hypertonia.

PMID- 24463895
TI  - Determinants of weight regain after bariatric surgery.
AB  - BACKGROUND: Bariatric surgery leads to an average loss of 60-75% of excess body
      weight with maximum weight loss in the period between 18 and 24 months
      postoperatively. However, several studies show that weight is regained from two
      years of operation. AIM: To identify the determinants of weight regain in post
      bariatric surgery users. METHODS: Prospective cross-sectional study with 64
      patients who underwent bariatric surgery with postoperative time > 2 years valued
      at significant weight regain. The variables analyzed were age, sex, education,
      socioeconomic status, work activity related to food, time after surgery, BMI,
      percentage of excess weight loss, weight gain, attendance monitoring nutrition,
      lifestyle, eating habits, self-perception of appetite, daily use of nutritional
      supplements and quality of life. RESULTS: There were 57 (89%) women and 7 (11%)
      men, aged 41.76 +/- 7.93 years and mean postoperative period of 53.4 +/- 18.4
      months. The average weight and BMI were respectively 127.48 +/- 24.2 kg and 49.56
      +/- 6.7 kg/m2 at surgery. The minimum weight and BMI were achieved 73.0 +/- 18.6
      kg and 28.3 +/- 5.5 kg/m2, reached in 23.7 +/- 12 months postoperatively.
      Regained significant weight occurred in 18 (28.1%) cases. The mean postoperative
      period of 66 +/- 8.3 months and work activities related to food showed
      statistical significance (p=000 and p=0.003) for the regained weight. CONCLUSION:
      Bariatric surgery promotes adequate reduction of excess body weight, with
      significant weight regain observed after five years; post-operative time and work
      activity related to eating out as determining factors for the occurrence of
      weight regain.

PMID- 24463896
TI  - Cluster analysis for classification of patients submitted to Fobi-Capella
      bariatric surgery.
AB  - BACKGROUND: Individuals classified as morbidly obese require effective treatments
      to promote weight reduction. Due to the inefficacy of conservative treatments and
      current medications, bariatric surgery (gastric bypass) has been indicated for
      this group of individuals. AIM: To identify subgroups of obese patients in order
      to find patterns that hinder weight loss and recovery after the operation.
      METHOD: Variables from the medical records of 50 patients were analyzed at two
      different times: before bariatric surgery and six months after the surgery,
      utilizing statistical cluster analysis. RESULTS: The analysis led to dividing the
      patients into two groups. The body mass index - BMI variable did not influence
      the classification of the patients. The group in worse metabolic conditions was
      not necessarily composed of heavier subjects, but the cluster analysis grouped
      the patients according to four indicators of metabolic syndrome. Metabolic
      alterations and blood pressure were shown to have a clear correlation to obesity,
      relation to BMI was not confirmed by this study. CONCLUSIONS: Taking measures to
      manage metabolic syndrome and not focusing solely on weight loss could improve
      recovery after bariatric surgery, considering that the BMI was reduced in all
      patients and was not the distinguishing factor for the postoperative period.

PMID- 24463897
TI  - Nonalcoholic steatohepatitis on preoperative period of gastric bypass: lack of
      correlation with degree of obesity.
AB  - BACKGROUND: Metabolic disorders have high correlation with severe forms of
      nonalcoholic fatty liver disease. However, there is no non-invasive method that
      promotes its proper stratification and biopsy remains the ideal diagnostic tool.
      AIM: To evaluate the prevalence of this disease in obese in preoperative period
      of Roux-en-Y gastric bypass and metabolic factors correlated with liver
      histopathology. METHODS: From a total of 47 patients, 35 were enrolled in the
      inclusion criteria and 12 excluded due to liver disease and alcohol intake >80
      g/week. Were performed clinical and laboratory evaluation before the surgery and
      intraoperative liver biopsy . The intensity was ranked in grade of
      steatohepatitis: I (mild to moderate) and II (diffuse inflammation), III (
      periportal fibrosis) and IV (cirrhosis). Were compared the following variables:
      duration of obesity, body mass index, waist-hip ratio, type 2 diabetes mellitus,
      hypertension and dyslipidemia. RESULTS: Thirty -five patients (68.6 % women ,
      mean age 37 years) were evaluated. The mean body mass index preoperatively was
      53.04 kg/m2. Nonalcoholic steatohepatitis was found in 31 patients (88.6 %) and
      32.2% were in grade I (n=10), grade II 45.2% (n=14), and 25.6% grade III (n=7).
      The waist-hip ratio was associated with hepatic steatosis; hypertriglyceridemia
      was the marker that had best correlation with higher grade; there was no
      correlation between aminotransferase and intensity of the disease; there was
      correlation of intensity with factors related to insulin resistance. CONCLUSION:
      Nonalcoholic steatohepatitis is highly prevalent in morbidly obese patients, but
      there was no positive correlation between aminotransferases and degree of obesity
      and liver histopathology. Hypertriglyceridemia and waist-hip ratio were
      positively correlated with the intensity of disease.

PMID- 24463898
TI  - Validation of ultrasound examination for assessment of the abdominal visceral fat
      in clinically serious obese patient.
AB  - BACKGROUND: Computerized tomography is the gold-standard for measurement of
      abdominal visceral fat. However, it is costly and involves submitting patients to
      ionizing radiation. AIM: To validate the use of ultrasonography in assessing
      abdominal visceral fat among clinically serious obese patients of both genders.
      METHODS: The sample included adult patients with clinically serious obesity with
      body mass index of 40 kg/m2 or from 35 kg/m(2) to 40 kg/m2 with co-morbidities.
      Abdominal visceral fat thickness was measured using ultrasound and tomography.
      Two ultrasonographic exams were conducted to assess the interobserver
      reproducibility among a patient subsample. Validation was done by comparing these
      results with the tomographic findings. RESULTS: The study included 13 patients
      (61.54% female) with an average BMI of 38.82 kg/m2. In terms of validation, the
      result obtained from applying the Pearson correlation coefficient was equal to
      0.94 (p = 0.0005), showing a strong positive correlation between the two
      measurements. As for the results for reproducibility, the interobserver was equal
      to 0.822, with a confidence interval of 95% (-0.076 to 0.980), revealing good
      interobserver agreement. The average difference between the two ultrasound
      interobserver examination was equal to 0.10 +/- 1.51 (p=0.8898) and so not
      significant. Interobserver bias was also not significant. CONCLUSION: The
      validation of ultrasonographic examination to replace tomographic method in
      assessing abdominal visceral fat among clinically serious obese patients was
      effective. The ultrasound measurement is independent of the examiner.

PMID- 24463899
TI  - Obese patients with diabetes mellitus type 2 undergoing gastric bypass in Roux-en
      Y: analysis of results and its influence in complications.
AB  - BACKGROUND: About 90% of type 2 diabetic patients are obese or overweight. The
      obvious clinical improvement observed with surgeries, such as Roux-en-Y gastric
      bypass, has opened space for research by different factors than only weight loss,
      as responsible for the return to euglycemia and reduction of medication use. AIM:
      To evaluate the efficacy and safety of surgical treatment of diabetes in obese
      patients with BMI above 35 kg/m2 underwent to gastric bypass, for the control of
      diabetes, weight loss, improvement of laboratory findings and complications of
      diabetes. METHOD: The protocol was implemented in three stages: initial, after
      losing 10% of weight, and after a year. RESULTS: Seventeen patients who have lost
      weight in 10% were included in the surgical protocol. From the total, 11.8%
      continued needing medication (p <0.001). The time for weight loss was a month
      with significant reduction in fasting glucose, HOMA-IR index, insulin, HbA1c,
      hemoglobin, AST, urea and C-peptide and there was no variation in hematocrit,
      albumin, ALT and creatinine. With a year of monitoring, the surgical group showed
      a significant difference in weight, BMI, blood glucose, HbA1c, C-peptide, insulin
      and HOMA-IR. The percentage of patients with neuropathy (31.3%) was lower than
      the number of cases at baseline (52.9%) (p> 0.05). CONCLUSION: Gastric bypass
      with Roux-en-Y derivation is a safe procedure, with good results in control of
      diabetes type 2 in obese patients with BMI above 35 kg/m2.

PMID- 24463900
TI  - Long-term mortality of patients submitted to Roux-en-Y gastric bypass in Public
      Health System: high prevalence of alcoholic cirrhosis and suicides.
AB  - BACKGROUND: Bariatric surgery is a valuable therapeutic option to severe obesity.
      Many researches have assessed the procedure efficiency on weight reduction,
      improvement in comorbidities and reduction of mortality. However, studies of late
      mortality and its causes are still necessary, mainly in the Brazilian population.
      AIM: To assess late mortality, discriminating causes of death and its association
      with pre-operative characteristics in a series of patients submitted to bariatric
      surgery. METHODS: Data analyses of 248 patients submitted to Roux-en-Y gastric
      bypass through Public Health System, from one up to 12 years of follow-up. The
      analyzed variables were: gender, age by the time of the surgery, pre-operative
      body mass index, comorbidities and smoking. The information about mortality was
      obtained through the Mortality Information System. The deaths were categorized
      according to International Classification of Diseases 10 and statistics analysis
      was done through the software STATA TM 9.2. RESULTS: There were nine deaths, five
      of them were female. The mean age of the patients who died was 48.3 +/- 8.4 years
      and the pre-operative body mass index was 56.0 +/- 7.4 kg/m2. The causes of death
      were: alcoholic cirrhosis (n=2), suicide (n=2), infectious causes (n=2),
      respiratory insufficiency (n=1), agranulocytosis (n=1) and unknown causes (n=1).
      None of the deaths was directly related to the surgery and there was no
      association of the pre-operative characteristics in mortality. CONCLUSION: There
      was not any association between late mortality and pre-operative characteristics.
      The high frequency of suicide and alcoholic cirrhosis mortality indicates the
      strict follow-up concerns, with appropriate psychological support to the
      patients.

PMID- 24463901
TI  - Metabolic surgery, weight regain and diabetes re-emergence.
AB  - INTRODUCTION: The poor success of clinical treatment of Type 2 Diabetes Mellitus
      (T2DM2) increased interest in metabolic surgery, which has been considered a
      promising alternative for the control of obese or non-obese diabetics. However,
      there is still no long-term follow-up to evaluate the duration of diabetes
      remission, and if weight regain would be associated to recurrence. AIM: 1) To
      describe the results of diabetic patients with a BMI < 30 and < 35 kg/m2
      submitted to the following types of metabolic surgery: ileal interposition and
      sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), adjustable gastric banding,
      duodeno-jejunal exclusion and duodeno-jejunal bypass; 2) to evaluate the possible
      relapse of diabetes after occurrence of weight regain on long-term after
      bariatric surgery. METHOD: An expositive and historical literature review about
      metabolic surgery in diabetic patients with BMI < 30 and < 35 kg/m2 was
      conducted, and systematic review of the association between disease relapse and
      weight regain after bariatric surgery. RESULTS: After analysis of 188 published
      papers on Medline until 2010, three papers were selected, which included 269
      patients who underwent RYGB. Pre-operatory BMI was between 37 and 60 kg/m2 and
      follow-up of three to 16 years. CONCLUSIONS: 1) Two studies showed association
      between weight regain and recurrence of type 2 diabetes, while the third did not
      show this association when comparing groups with and without weight regain; 2)
      metabolic surgery has shown adequate control of T2DM2 in class I obese subjects;
      however, the non-obese group still need a long-term evaluation, considering the
      risk of diabetes recurrence when after weight regain.

PMID- 24463902
TI  - Micronutrient deficiencies in the pre-bariatric surgery.
AB  - INTRODUCTION: Data already demonstrated the increased prevalence of obesity in
      various segments of the population. In this context, bariatric surgery is
      accepted nowadays as the most effective tool in the treatment and control of
      morbid obesity. Several studies have evaluated the nutritional status after
      bariatric surgery, especially mixed by detecting a reduction in food intake of
      protein, vitamins and minerals. However, other studies have investigated the
      presence of nutritional deficiencies prior to surgery, which may be aggravated by
      the surgical procedure, resulting in serious postoperative complications. AIM: To
      analyze the literature in relationship to micronutrient deficiencies in obese
      patients before bariatric surgery. METHOD: Was carried out a systematic review in
      several electronic databases, such as PubMed/ Medline, Scielo, Lilacs and Bireme.
      The following keywords were used alone or in combination: bariatric surgery,
      obesity, preoperative, gastric bypass, vitamin deficiencies, deficiencies and
      mineral nutrient absorption. Were included 40 review and original articles
      published between 2005 to 2012. RESULTS: There were consensus on the combination
      of preoperative nutritional deficiencies, restrictions and malabsorption,
      possibly induced by bariatric surgery that can lead patients to experience
      significant nutritional deficits during the late postoperative period, especially
      of micronutrients, resulting in serious complications. CONCLUSIONS: The high
      occurrence of micronutrient deficiencies preoperatively detected in morbidly
      obese candidates for bariatric surgery, plus a malabsorptive procedure, may
      involve worse prognosis during the late postoperative period. Preoperative
      evaluation of nutritional parameters and food intake is recommended in
      conjunction with surgical interventions.

PMID- 24463903
TI  - Physical exercise and morbid obesity: a systematic review.
AB  - INTRODUCTION: Physical exercise is an important component for the treatment of
      obesity. Little information is available about the best and safety form of
      physical exercise concerning the type and volume-intensity to be prescribed for
      individuals with morbid obesity. AIM: To investigate the effect of physical
      exercise programs in medical and surgical treatment for morbid obesity. METHODS:
      Was used the systematic search model by databases of the Virtual Health Library
      in "Science in General Health" (Medline, Lilacs and Ibecs) and PubMed using the
      following headings: morbid obesity, severe obesity, grade 3 obesity, exercise and
      physical activity. Were selected papers that used physical exercise programs as
      an intervention in the treatment for morbid obese patients and those who were in
      accordance with the inclusion criteria. RESULTS: Were selected 13 articles. Eight
      were conducted with individuals in clinical treatment, one in patients awaiting
      bariatric surgery and four in the postoperative period. It was observed that all
      selected studies used aerobic activities and six also included strength exercises
      on their programs. CONCLUSIONS: Aerobic and strength exercises programs proved
      being important components in the treatment of morbid obesity. Special care when
      establishing the volume-intensity exercise is required for adherence to
      treatment, and a proposal for a valid individualized exercise programs.

PMID- 24463905
TI  - Gastric sleeve fixation strategy in laparoscopic vertical sleeve gastrectomy.
AB  - INTRODUCTION: Initially conceived as the first of two stages in operations such
      as gastric bypass or duodenal switch in high-risk patients, laparoscopic vertical
      sleeve gastrectomy has increasingly become the definitive procedure for treating
      obesity and its comorbidities. Although it is associated with excellent results
      and postoperative quality of life, a number of complications related to improper
      position and/or gastric tube deformities, resulting from loss of natural
      fixation, may be associated to symptoms of persistent food intolerance and/or
      gastroesophageal reflux. AIM: To present the gastric fixation strategy in
      vertical sleeve gastrectomy for the treatment of obesity and related diseases.
      TECHNIQUE: The gastric suture line along the "new greater curvature" is divided
      into two parts. Using non-absorbable 2.0 polyester thread, a continuous suture
      fixation is made in the proximal part attaching it to the free edge of the
      gastrocolic ligament with invagination. Separate sutures were applied to the
      distal part, including the transverse mesocolon near the lower edge of the
      pancreas. CONCLUSION: The stomach fixation strategy is easy to use, safe and can
      reduce complications arising from improper positioning and gastric tube
      alterations in laparoscopic vertical sleeve gastrectomy, particularly symptoms
      related to food intolerance and gastroesophageal reflux.

PMID- 24463904
TI  - Technical modification for sleeve gastrectomy.
AB  - INTRODUCTION: The surgical technique of sleeve gastrectomy has not been fully
      standardized and, therefore, there are issues to be solved. There is a tendency
      to increase its application due to proved efficiency in weight loss, low
      morbidity and good postoperative results. However, gastroesophageal reflux
      disease, which can result from it, is still not well understood. AIM: To present
      variant technique for sleeve gastrectomy that leaves the stomach totally with the
      appearance of a homogeneous tube, without manipulation in pyloric and lower
      esophageal sphincters. TECNIQUE: Vertical gastrectomy starts with vessel ligation
      of the greater curvature at the pylorus till esophagogastric angle. Stapling also
      starts from the pylorus in the same direction. For modeling was used Fouchet 32 F
      and all the staple line was done just to it. At the end, oversuture of the staple
      line and "sump" drainage were done. RESULTS: The procedure was used in 55
      patients with BMI between 35 and 41. Complications in this group were two
      fistulas at the esophagogastric angle, one twist of the gastric tube and one
      postoperative conversion to Roux-en-Y gastric bypass due to untreatable
      gastroesophageal reflux disease. Fistulas were treated by endoscopic procedure
      with dilation and septotomy. Mild dysphagia due to tube twisting responded
      satisfactorily to dilatation. The longest follow-up was two years. The loss of
      overweight was 67.7% at one year and 69.7% in two. Patients who were suffering
      from type 2 diabetes mellitus showed disease control in 84.6 % in the first year
      and 91.6 % in the second. Comorbidities were controlled in all cases. CONCLUSION:
      The variant technique proposed here for sleeve gastrectomy leaves the stomach
      homogeneously in a shape of a tube and in small caliber, providing small free
      gastric cavity and keeping natural functional activity of the sphincters.
      However, it may lead to unwanted gastroesophageal reflux, which needs to be
      better measured in future research.

PMID- 24463906
TI  - Laparoscopic Roux-en-Y gastric bypass with single transumbilical incision-
      GelPoint(r).

PMID- 24463907
TI  - Clostridium difficile and cytomegalovirus colitis coinfection after bariatric
      surgery: case report.

PMID- 24463908
TI  - Anatomical and functional volume concordance between FDG PET, and T2 and
      diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study.
AB  - PURPOSE: To evaluate the concordance among (18)F-FDG PET imaging, MR T2-weighted
      (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion
      weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR. METHODS:
      This study prospectively included 35 patients with cervical cancer who underwent
      pretreatment (18)F-FDG PET/MR imaging. (18)F-FDG PET and MR images were fused
      using standard software. The percent of the maximum standardized uptake values
      (SUV max) was used to contour tumours on PET images, and volumes were calculated
      automatically. Tumour volumes measured on T2-W and DW images were calculated with
      standard techniques of tumour area multiplied by the slice profile. Parametric
      statistics were used for data analysis. RESULTS: FDG PET tumour volumes
      calculated using SUV max (14.30 +/- 4.70) and T2-W imaging volume (33.81 +/-
      27.32 cm(3)) were similar (P > 0.05) at 35 % and 40 % of SUV max (32.91 +/- 18.90
      cm(3) and 27.56 +/- 17.19 cm(3) respectively) and significantly correlated (P <
      0.001; r = 0.735 and 0.766). The mean DW volume was 30.48 +/- 22.41 cm(3). DW
      volumes were not significantly different from FDG PET volumes at either 35 % SUV
      max or 40 % SUV max or from T2-W imaging volumes (P > 0.05). PET subvolumes with
      increasing SUV max cut-off percentage showed an inverse change in mean ADC values
      on DW imaging (P < 0.001, ANOVA). CONCLUSION: Hybrid PET/MR showed strong volume
      concordance between FDG PET, and T2-W and DW imaging in cervical cancer. Cut-off
      at 35 % or 40 % of SUV max is recommended for (18)F-FDG PET/MR SUV-based tumour
      volume estimation. The linear tumour subvolume concordance between FDG PET and DW
      imaging demonstrates individual regional concordance of metabolic activity and
      cell density.

PMID- 24463909
TI  - European Association of Nuclear Medicine: adapt the present, shape the future.

PMID- 24463910
TI  - Overuse injuries and burnout in youth sports: a position statement from the
      American Medical Society for Sports Medicine.

PMID- 24463911
TI  - 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return
      to Play of the Female Athlete Triad: 1st International Conference held in San
      Francisco, California, May 2012 and 2nd International Conference held in
      Indianapolis, Indiana, May 2013.
AB  - The Female Athlete Triad is a medical condition often observed in physically
      active girls and women, and involves three components: (1) low energy
      availability with or without disordered eating, (2) menstrual dysfunction and (3)
      low bone mineral density. Female athletes often present with one or more of the
      three Triad components, and an early intervention is essential to prevent its
      progression to serious endpoints that include clinical eating disorders,
      amenorrhoea and osteoporosis. This consensus statement represents a set of
      recommendations developed following the 1st (San Francisco, California, USA) and
      2nd (Indianapolis, Indiana, USA) International Symposia on the Female Athlete
      Triad. It is intended to provide clinical guidelines for physicians, athletic
      trainers and other healthcare providers for the screening, diagnosis and
      treatment of the Female Athlete Triad and to provide clear recommendations for
      return to play. The 2014 Female Athlete Triad Coalition Consensus Statement on
      Treatment and Return to Play of the Female Athlete Triad expert panel has
      proposed a risk stratification point system that takes into account magnitude of
      risk to assist the physician in decision-making regarding sport participation,
      clearance and return to play. Guidelines are offered for clearance categories,
      management by a multidisciplinary team and implementation of treatment contracts.
      This consensus paper has been endorsed by the Female Athlete Triad Coalition, an
      International Consortium of leading Triad researchers, physicians and other
      healthcare professionals, the American College of Sports Medicine and the
      American Medical Society for Sports Medicine. 

PMID- 24463912
TI  - A handmade eye movement monitor using a piezoelectric device during
      transsphenoidal surgery.
AB  - We describe a handmade eye movement monitor featuring a piezoelectric device for
      use during transsphenoidal surgery (TSS). The sensor consists of a piezoelectric
      device, condensers, resistors, and several inexpensive parts. Eyeball movements
      elicited by surgical manipulations during TSS for cavernous sinus tumor are
      detected by small disc-shaped sensors taped to the eyelids. The responses could
      be monitored as sharp waves on an electroencephalograph. After we started using
      this monitor, both the incidence and the severity of cranial nerve injuries
      during TSS for cavernous sinus tumor decreased. Our device is especially useful
      at operations to remove functioning pituitary adenomas invading the cavernous
      sinus and contributes to their favorable endocrine outcomes. None of our patients
      manifested the postoperative swelling of the eyelids or conjunctival congestion
      generally seen in patients subjected to the insertion of needle sensors for the
      acquisition of electromyograms of the extraocular muscles, which is widely used
      during surgery to identify the cranial nerves responsible for eye movement. Our
      monitor is less expensive and easier to use than any commercially available
      sensor devices. As our method does not require the insertion of needle sensors,
      it is less invasive than electromyography of the extraocular muscles. 

PMID- 24463913
TI  - Surgical management of ocular symptoms in spheno-orbital meningiomas. Is orbital
      reconstruction really necessary?
AB  - Spheno-orbital meningioma (SOM) is an intriguing tumor because of the many
      different factors that can influence clinical and oncological outcome after
      treatment. Reasoning that outcome indicator measurement is key to improving
      therapy, we retrospectively evaluated the management of proptosis and other
      ocular symptoms in 47 patients surgically treated for SOM at our department in
      the last 10 years. This patient series was characterized by a high rate of tumor
      infiltration of the extradural cranial base. Clinical outcome was assessed by
      comparing preoperative and postoperative ophthalmological and neurological signs.
      Acute postoperative complications were reported, and clinical and radiological
      outcome was assessed at 4-6 months, 12 months, and the last follow-up. Proptosis
      (measured by Hertel exophthalmometry), visual acuity, visual field defect
      (measured by Goldmann perimetry), diplopia (measured by the Hess-Lancaster test),
      and other disturbances were rated as normalized, improved, or unchanged/worsened.
      The most common presenting symptoms were proptosis (95.7%), visual impairment
      (51%), and cranial nerve deficit (38.2%). Surgery via the frontotemporal approach
      was performed in all 47 cases, with the primary aim to relieve symptoms/signs and
      maximize tumor resection. Bony orbital reconstruction was never performed.
      Complete resection was achieved in 51% of cases (Simpson grades I and II) with
      minimal morbidity. At a mean follow-up of 52 months (range, 12-112), proptosis
      normalized in 90.9% and improved in the remaining patients, visual acuity
      normalized in 20.8% and improved in 45.8% patients, cranial nerve deficit
      subsided in all but two cases. The recurrence rate was 29.7%. One of the gold
      standards of surgical treatment, normalization of proptosis, can be achieved by
      accurate resection of the superior and lateral orbital walls. In this setting,
      careful reconstruction of the frontobasal dura is far superior to bony
      reconstruction. Complete tumor resection should not be pursued at the expense of
      increased morbidity.

PMID- 24463915
TI  - The relationship between low-density lipoprotein cholesterol levels and the
      incidence of cardiovascular disease in high-risk patients treated with
      pravastatin: main results of the APPROACH-J study.
AB  - This study aimed to evaluate the relationship between low-density lipoprotein
      cholesterol (LDL-C) levels and cardiovascular disease (CVD) in high-risk patients
      with hypercholesterolemia without a history of CVD. Patients who were receiving
      or started treatment with pravastatin, were followed-up for 2 years. Patients
      were divided into quartiles according to on-treatment LDL-C. The maximum contrast
      method based on the Cox proportional hazards model was used to evaluate the
      relationship between achieved LDL-C and the incidence of CVD. Incidence of CVD
      was also compared according to whether a number of risk factor targets were
      achieved. A total 6,229 patients were enrolled, with 4,916 having reported LDL-C
      values. During the 2 years, 69 cases of CVD (6.7/1000 patient years), including
      36 coronary artery disease (CAD) (3.5/1000 patient years) and 28 strokes
      (2.7/1000 patient years), occurred. The comparison of on-treatment LDL-C level
      quartiles suggested that the incidence of all CVD decreased linearly as the LDL-C
      levels decreased. Incidence of CAD showed a curvilinear relationship to LDL-C
      levels, suggesting some attenuation of risk below LDL-C of 119 mg/dL. The
      incidence of all CVD and CAD tended to be decreased as the number of achieved
      risk factor targets increased. In conclusion, through our observational study, it
      was shown that a linear relationship between the incidence of CVD and LDL-C was
      observed in high-risk hypercholesterolemic patients. The low incidence of CVD in
      the present study may be associated with multifactorial management of
      conventional risk factors including high LDL-C levels. However, prospective,
      randomized studies are needed to confirm these findings. 

PMID- 24463914
TI  - Silicone models as basic training and research aid in endovascular
      neurointervention--a single-center experience and review of the literature.
AB  - The rapid development and wider use of neurointerventional procedures have
      increased the demand for a comprehensive training program for the trainees, in
      order to safely and efficiently perform these procedures. Artificial vascular
      models are one of the dynamic ways to train the new generation of
      neurointerventionists to acquire the basic skills of material handling, tool
      manipulation through the vasculature, and development of hand-eye coordination.
      Herein, the authors present their experience regarding a long-established
      training program and review the available literature on the advantages and
      disadvantages of vascular silicone model training. Additionally, they present the
      current research applications of silicone replicas in the neurointerventional
      arena. 

PMID- 24463916
TI  - A case report of persistent fifth aortic arch presenting with severe left
      ventricular dysfunction.
AB  - According to several previous reports on persistent fifth aortic arch (PFAA), the
      presentation of the patients was usually either very mild when diagnosed by
      physical examination including upper body systemic hypertension and systolic
      murmur, or severe with ductal shock in the neonatal period. In our case, the
      clinical course was unique with relatively mild narrowing at the distal PFAA and
      an interrupted fourth aortic arch. It can be classified as medium severity based
      on the timing of presentation to the hospital. In the present case, severe LV
      dysfunction suggested sustained narrowing at the junction between the PFAA and
      the descending aorta and insufficient development of collateral arteries.We
      experienced a case with PFAA with severe LV dysfunction. These findings suggest
      another differential diagnosis for severe LV dysfunction in infancy. 

PMID- 24463917
TI  - Transcatheter closure of late-onset residual aortopulmonary septal defect using a
      muscular ventricular septal occluder.
AB  - Late-onset residual shunt after surgical repair of aortopulmonary septal defect
      (APSD) is a rare event complicating the management strategy. Surgical reoperation
      was the treatment of choice traditionally, while associated with increased risk
      and suffering. We report a case of successful treatment of this type of residual
      shunt using a transcatheter closure technique with an infrequently used muscular
      ventricular septal device. 

PMID- 24463918
TI  - Successful ablation of atypical atrioventricular nodal reentrant tachycardia from
      a noncoronary sinus of Valsalva.
AB  - An 81-year-old man with long RP narrow QRS tachycardia underwent catheter
      ablation. Ventricular pacing reset the atrial cycle over a retrograde slow
      pathway, followed by termination of the tachycardia without atrial capture,
      confirming the diagnosis of fast-slow atrioventricular nodal reentrant
      tachycardia (AVNRT). The earliest atrial activation during tachycardia was found
      in the noncoronary sinus of Valsalva, where the first delivery of radiofrequency
      energy terminated and eliminated the inducibility of the tachycardia, by
      retrograde conduction block over the slow pathway. This is the first report of a
      fast-slow AVNRT, with successful ablation of the slow pathway from a noncoronary
      sinus of Valsalva. 

PMID- 24463919
TI  - Toward the development of bioengineered human three-dimensional vascularized
      cardiac tissue using cell sheet technology.
AB  - Bioengineered cardiac tissue is expected to be applied to regenerative medicine
      and tissue models for disease research and drug screening. Recent and rapid
      progress in technologies for tissue engineering approaches, including cell sheet
      technology, vascularization of thickened tissues, and large-scale expansion and
      differentiation of pluripotent stem cells, is about to realize the fabrication of
      human three-dimensional cardiac tissue. However, a remaining challenge is to make
      these fabricated tissues closely resemble the phenotypes, and to perform the
      functions of human cardiac tissue. 

PMID- 24463920
TI  - Comparison of prognostic value of red cell distribution width and NT-proBNP for
      short-term clinical outcomes in acute heart failure patients.
AB  - Comparison of the prognostic value of red cell distribution width (RDW) and N
      terminal pro B-type natriuretic peptide (NT-proBNP) for short-term clinical
      outcomes in acute heart failure (AHF) patients has not been fully investigated.A
      total of 128 patients with AHF were enrolled and followed for 3 months. Primary
      endpoints were cardiovascular (CV) events, defined as cardiac death and/or
      readmission for HF. Baseline RDW and NT-proBNP were measured at admission.The 30
      day and 90-day CV event rates were 16.4% and 35.9%, respectively. NT-proBNP was
      higher in people with cardiovascular events at both time points, while RDW was
      significantly higher only at the 90-day time point. The area under the ROC curve
      of RDW (area under the ROC curve = 0.695) for the prediction of CV events was
      higher than that of NT-proBNP (area under the ROC curve = 0.610) at the 90-day
      time point, but lower at the 30-day time point. Cox hazard analysis revealed RDW
      and NT-proBNP were independent predictive factors of a 90-day CV event (RDW,
      hazard ratio, 4.610, 95% confidence interval 1.935-10.981, P = 0.001; NT-proBNP,
      hazard ratio, 3.661, 95% confi dence interval 1.125-11.907, P = 0.031). Kaplan
      Meier survival analysis revealed that patients with an RDW level > 14.5% and NT
      proBNP > 1471.5 pg/mL were at highest risk for a CV event (P < 0.001).RDW and NT
      proBNP are strong independent predictors of 90-day cardiovascular events in
      patients hospitalized with AHF. RDW can add prognostic value to NT-proBNP for
      predicting early cardiovascular events. 

PMID- 24463921
TI  - Coronary artery bypass surgery: beating heart or cardiopulmonary bypass?
AB  - In this study, we examined the early results for patients who underwent beating
      heart coronary bypass surgery and compared these results with those of
      conventional coronary bypass surgery.A total of 1094 patients who underwent
      isolated coronary artery bypass surgery between January 2009 and December 2011 in
      our clinic were included in this study. Seventy-three patients in whom
      cardiopulmonary bypass was not used (group 1) were compared to 1021 patients in
      whom cardiopulmonary bypass was used (group 2).The mean age was 60.7 +/- 9.3 in
      group 1 and 58.9 +/- 9.7 in group 2 (P > 0.05). There was no significant
      difference between the two groups in terms of gender, or the coexistence of
      diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and
      hypertension (P > 0.05). There was no significant difference between group 1 and
      group 2 in terms of development of postoperative atrial fibrillation (AF), use of
      an intra-aortic balloon pump, need for re-operation for bleeding, or duration of
      hospital stay and intensive care unit stay (P > 0.05). The need for inotropic
      support and the amount of mediastinal drainage were less in group 1 than in group
      2 (P = 0.002, P < 0.001). The incidences of postoperative cerebrovascular
      accident, development of chronic renal failure, and sternal wound infection did
      not significantly differ between the groups (P > 0.05). There was no mortality in
      group 1, whereas it was calculated as 1.8% in group 2 (P = 0.63).Beating heart
      coronary artery bypass surgery decreases the need for inotropic support and
      transfusion.

PMID- 24463922
TI  - Human atrium transcript analysis of permanent atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is
      associated with increased risks of stroke and heart failure. However, the exact
      mechanisms of left atrium remodeling and AF-related biological behaviors are not
      completely understood.The transcripts of left atrium in permanent atrium
      fibrillation patients (n = 7) were compared with those of healthy heart donors (n
      = 4) in sinus rhythm using Agilent 4x44K microarrays. Differently expressed genes
      were analyzed based on Gene Ontology and KEGG and Biocarta pathway analysis
      databases.We identified 567 down- and 420 up-regulated genes in atrial
      fibrillation. The majority of the down-regulated genes participated in metabolic
      processes, particularly that for fatty acids. The most remarkable up-regulating
      effects were immune and platelet activation. In addition, atrial remodeling
      including structural, contractile, electrophysiological, neurohormone, and
      oxidant stress was also observed, suggesting various pathophysiology changes in
      fibrillating atrium. Nine AF closely related genes were validated by real-time RT
      PCR.Some AF specific genes were determined which may be a complement to the
      mechanism of left atrium remodeling. Metabolic changes and inflammation could
      promote or aggravate atrial fibrillation.

PMID- 24463923
TI  - Time-domain heart rate variability in coronary artery disease patients affected
      by thyroid dysfunction.
AB  - Subclinical hypothyroidism and hyperthyroidism have been recognized as clinical
      entities with negative effects on the cardiovascular system. Moreover, the effect
      of treated thyroid dysfunction on parameters associated with the cardiovascular
      control system has been poorly investigated. In the present study we analyzed
      time-domain heart rate variability in coronary artery disease (CAD) patients with
      known thyroid diseases. Twenty-four hour ECG monitoring was performed in 344
      patients with coronary artery disease (174 with thyroid dysfunction and 170
      without thyroid dysfunction used as a control group), using a 3-channel tape
      recorder. Time domain parameters of heart rate variability (HRV) were definitely
      lower both in patients with subclinical hypothyroidism and subclinical
      hyperthyroidism than in the control group, with statistically significant
      differences in SDNN, RMSSD, TINN, and mean RR for both subgroups. Furthermore,
      patients on L-thyroxine treatment and restored euthyroidism had generally higher
      HRV values than patients with subclinical hypothyroidism, nevertheless SDNN,
      RMSSD, SDNN index, TINN, and mean RR were significantly lower when compared to
      those of the control group. Significant differences in HRV were also found
      between hyperthyroid patients under treatment and control group subjects with
      respect to RMSSD, TINN, and mean RR values. In conclusion, patients with cardiac
      disease and known thyroid disease, even when the disease is in the subclinical
      range or despite treatment, should be regarded as patients at additional risk
      conveyed by thyroid hormone disturbances.

PMID- 24463924
TI  - Effect of direct renin inhibitor on left ventricular remodeling in patients with
      primary acute myocardial infarction.
AB  - Some patients with acute myocardial infarction (AMI) have a poor prognosis due to
      left ventricular remodeling (LVR), resulting in the recurrence of congestive
      heart failure even when therapy with angiotensin-converting enzyme inhibitors
      (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been initiated. We
      investigated the effect of early administration of the direct renin inhibitor
      (DRI) aliskiren in combination with an ACEI or an ARB on LVR using cardiac
      magnetic resonance (CMR) imaging in patients with AMI.Twenty-one consecutive
      patients were treated with an ACEI or an ARB (non-DRI group), and another 21
      consecutive patients received aliskiren 150 mg/day combined with an ACEI or an
      ARB (DRI group). CMR imaging was performed 7 days after AMI and 10 months
      later.CMR imaging revealed no significant changes in LV end-systolic volume, LV
      end-diastolic volume, or LV ejection fraction between the patients with and
      without DRI aliskiren. In the DRI group, plasma renin activity was significantly
      lower in both the acute and chronic phases; however, aldosterone levels were
      significantly lower in the acute but not the chronic phase.A low dose of
      aliskiren may be insufficient to maintain suppression of aldosterone under
      current standard therapies with an ACEI or an ARB and beta-blocker in patients
      with primary AMI, and results in no attenuation of LVR.

PMID- 24463925
TI  - Plaque quantification by coronary CT and intravascular ultrasound identifies a
      low CT density core as a marker of plaque instability in acute coronary
      syndromes.
AB  - The purpose of this study was to demonstrate the relationship between the
      presence and amount of a low-density core (LDC) with a CT density < 30 Hounsfield
      units (HU) by coronary computed tomography angiography (CCTA) and IVUS-derived
      markers of vulnerability in the culprit lesions (CL) of patients with acute
      coronary syndromes (ACS).In 43 patients with ACS, 105 coronary plaques were
      scanned using CCTA and IVUS for the quantitative and qualitative assessment of
      vulnerability markers.The presence of a low attenuation plaque (LAP) was
      identified in 67.4% of the CL and 29.03% of the non-CL (P = 0.0001). The presence
      of a LDC > 6.0 mm(3) was significantly correlated with the percentage of the
      necrotic core (NC) (22.08% versus 7.97%, P = 0.001) and the fibro-fatty tissue by
      IVUS (18.68% versus 15.87%, P = 0.02). LDC volumes showed a good correlation with
      the percentage of the NC (r = 0.7303, P < 0.0001) and the fibro-fatty tissue in
      the CL (r = 0.4928, P < 0.0008). Quantitative plaque analysis revealed a
      significant difference in plaque composition between CL and non-CL in regards to
      the LDC (18.45 versus 6.5, P < 0.001), the percentage of NC (20.74 versus 18.74,
      P = 0.02), fibro-fatty tissue (17.77 versus 15.48, P = 0.002), and fibrotic
      tissue (51.68 versus 54.8, P = 0.01).VH-IVUS and CCTA plaque quantification
      showed that the presence of a low-density (< 30 HU) core within the CL of
      patients with ACS represents a marker of vulnerability and correlates well with
      other CCTA and IVUS-derived features of vulnerability, particularly the NC of the
      plaque. 

PMID- 24463926
TI  - Nonculprit lesion progression in patients with ST elevation myocardial infarction
      after primary percutaneous coronary intervention.
AB  - The majority of cardiovascular events in patients with ST elevation myocardial
      infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI)
      arise from the progression of nonculprit lesions (NCL) during the long-term
      follow-up period. However, the clinical and angiographic factors related to the
      progression of nonculprit lesions are unknown.The purpose of the study was to
      investigate the clinical and angiographic factors related to the progression of
      nonculprit lesions of patients with STEMI undergoing PPCI.A total of 492 patients
      with STEMI who underwent PPCI from January 2006 to December 2009 were enrolled.
      All patients underwent PPCI as a treatment for the culprit lesion. The clinical
      and angiographic follow-up was performed at 12 months. Primary endpoint:
      Clinically driven nonculprit lesion PCI. The levels of serum catecholamines
      [epinephrine (E), norepinephrine (NE)] and C-reactive protein (CRP) were assayed,
      and the clinical and angiographic features were also analyzed.The clinical and
      angiographic follow-up was performed in 492 patients, and 45 patients underwent
      clinically driven nonculprit lesions PCI (study group). A total of 447 patients
      were free of additional PCI (control group). There were significant differences
      in the level of catecholamines (E (621.48 +/- 79.31) pg/mL versus (268.14 +/-
      73.26) pg/mL, P < 0.0001), NE (6212.43 +/- 822.41) pg/mL versus (3218.34 +/-
      614.16) pg/mL, P < 0.0001), CRP (3.29 +/- 1.31) mg/dL versus (2.51 +/- 1.14)
      mg/dL, P < 0.0001, cTnI peak value (27.27 +/- 4.02) ng/mL versus (16.12 +/- 3.23)
      ng/mL, P < 0.0001), thrombotic lesion rate ((62.22% versus 23.04%), P < 0.0001),
      >= 2 vessel lesions rate (80.00% versus 46.09%), P < 0.0001), culprit lesion
      length ((33.2 +/- 2.9 versus 28.1 +/- 3.1), P = 0.013), and complex lesion rate
      ((57.78% versus 36.02%), P = 0.006) between the two groups. Correlation analysis
      between nonculprit lesion stenosis degree and serum E, serum NE, serum CRP, cTnI
      peak value, thrombotic lesion rate, >= 2 vessel lesions rate, culprit lesion
      length, and complex lesion rate showed that there were significant correlations
      between serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, >=
      2 vessel lesions rate, culprit lesion length, complex lesion rate, and nonculprit
      lesion stenosis degree. The correlation coefficients were 0.95, 0.97, 0.83, 0.90,
      0.81, 0.84, 0.95, and 0.96, respectively, and P < 0.0001, P < 0.0001, P = 0.01, P
      = 0.01, P = 0.01, P = 0.01, P < 0.0001, and P < 0.0001, respectively.Recurrent
      PCI was mainly due to nonculprit lesion progression in patients with STEMI after
      primary PCI. Complex nonculprit lesions may be prone to for additional PCI.
      Chronic inflammation and sustained stress may be involved in the progression of
      nonculprit lesions in patients with STEMI. 

PMID- 24463927
TI  - Natriuretic peptides as an adjunctive treatment for acute myocardial infarction:
      insights from the meta-analysis of 1,389 patients from 20 trials.
AB  - Animal studies have reported a cardioprotective effect for atrial natriuretic
      peptide (ANP) or brain natriuretic peptide (BNP) administration in the setting of
      acute myocardial infarction (AMI). However, previous trials performed on AMI
      patients have reported differences in the cardiac function protection for ANP/BNP
      infusion, making it diffi cult to confirm the beneficial effect of natriuretic
      peptides. We performed a meta-analysis of all available trials to determine
      whether ANP/BNP infusion was effective in improving cardiac function. METHODS: We
      searched various databases including PubMed, EMBASE, Web of Knowledge, the
      Cochrane Library, and CKNI for studies related to ANP/BNP infusion in AMI. The
      major outcome was left ventricular ejection fraction (LVEF). RESULTS: Twenty
      trials (4 for ANP, 16 for BNP) with 1389 patients were included. There were no
      significant differences in patient characteristics between the ANP/BNP infusion
      and control groups at baseline. Pooled analysis showed that patients in the
      ANP/BNP infusion group had significantly higher LVEF than in the control during
      follow-up [Studies on ANP: weighted mean differences (WMD) 2.94%, 95% confidence
      interval (CI): 1.39%-4.50%, P = 0.0002; Studies on BNP: WMD 4.45%, 95%CI: 2.25%
      6.65%, P < 0.0001]. CONCLUSIONS: The present meta-analysis suggested that ANP/BNP
      infusion might be effective in protecting left ventricular function in patients
      with AMI. ANP/BNP infusion may be an effective adjunctive therapy for cardiac
      function protection in AMI patients.

PMID- 24463928
TI  - Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias
      induced by a single injection of adrenaline.
AB  - We have recently demonstrated that basal cardiomyopathy develops in rabbits with
      ventricular tachyarrhythmias that have been induced by electrical stimulation of
      the cervical vagus. This study investigated whether similar basal cardiomyopathy
      would develop in rabbits with ventricular tachyarrhythmias induced by a single
      injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds
      in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion.
      Wall movement velocity of the left ventricular base was assessed by tissue
      Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later.
      Pathological lesions were identified by deposits of carbon particles. Animals
      were divided into two groups according to the infused dose of adrenaline. The
      small-dose group (group S, n = 15) received 1-10 MUg and the large-dose group
      (group L, n = 23) received 15-60 MUg of adrenaline. Adrenaline infusion induced
      premature ventricular contractions followed by monomorphic ventricular
      tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group
      S. Wall movement velocity of the left ventricular base decreased just after
      adrenaline infusion, remained low after 1 week, and recovered to near-baseline
      levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits
      of carbon particles were frequently observed on the left ventricular basal
      portion, almost always associated with the mitral valve and papillary muscles,
      but were never observed in the apical area. Lesions involving all areas of the
      left ventricular basal portion were observed in 22 of 23 animals in group L, but
      in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits
      with ventricular tachycardias induced by a single injection of adrenaline. 

PMID- 24463929
TI  - Serum uric acid is associated with the left ventricular mass index in males of a
      general population.
AB  - The association of serum uric acid (UA) with left ventricular hypertrophy (LVH)
      remains controversial. We investigated this issue in a general population.
      Participants consisted of 1,943 subjects (774 males and 1,169 females) aged over
      40 years, living in Tanushimaru (a Japanese cohort of the Seven Countries Study).
      Serum UA and other biochemistry parameters were determined by a standard
      analytical technique. All individuals underwent anthropometric measurements and 2
      dimensional echocardiography. Because serum UA levels are much higher in males
      than in females, they were analyzed separately. When LV mass index (LVMI) levels
      were stratified according to tertile as low (<= 80 cm(2): n = 261), middle (81
      103 cm(2): n = 261), and high (>= 104 cm(2): n = 252) in males, there were
      significant relationships between LVMI and UA, in addition to age, body mass
      index, systolic blood pressure, medication for hypertension, triglycerides, and
      alcohol intake. Multiple stepwise regression analysis revealed LVMI was
      significantly associated with systolic BP (P < 0.0001), medication for
      hypertension (P < 0.0001), UA (P = 0.003), BMI (P = 0.019), and alcohol intake (P
      = 0.038) in males. In females, LVMI was not associated with UA. In a multiple
      logistic regression analysis, a significantly higher odds ratio of LVH (odds
      ratio: 1.77, 95%CI: 1.01-3.09, P < 0.05) was observed for males in the highest UA
      tertile versus the lowest UA tertile after adjustments for confounding factors,
      but not for females. In this cross-sectional study, there was a clear difference
      in the relation of UA and LVH between males and females. High serum UA was
      significantly and independently associated with LVH evaluated by echocardiography
      in only males of a general population.

PMID- 24463930
TI  - Efficacy of intrathoracic impedance and remote monitoring in patients with an
      implantable device after the 2011 great East Japan earthquake.
AB  - Several studies have revealed that stress after catastrophic disasters can
      trigger cardiovascular events, however, little is known about its association
      with the occurrence of heart failure in past earthquakes. The objective of the
      present study was to determine whether the Great East Japan Earthquake on March
      11, 2011, increased the incidence of worsening heart failure in chronic heart
      failure (CHF) patients with implantable devices. Furthermore, we examined whether
      intrathoracic impedance using remote monitoring was effective for the management
      of CHF.We enrolled 44 CHF patients (32 males, mean age 63 +/- 12 years) with
      implantable devices that can check intrathoracic impedance using remote
      monitoring. We defined the worsening heart failure as accumulated impedance under
      reference impedance exceeding 60 ohms-days (fluid index threshold), and compared
      the incidence of worsening heart failure and arrhythmic events 30 days before and
      after March 11.Within the 30 days after March 11, 10 patients exceeded the
      threshold compared with only 2 patients in the preceding 30 days (P < 0.05).
      Although 9 patients using remote monitoring among the 10 patients with threshold
      crossings were not hospitalized, one patient without the system was hospitalized
      due to acute decompensated heart failure. On the contrary, arrhythmic events did
      not change between before and after March 11.Our results suggest that earthquake
      induced stress causes an increased risk of worsening heart failure without
      changes in arrhythmia. Furthermore, intrathoracic impedance using remote
      monitoring may be a useful tool for the management of CHF in catastrophic
      disasters. 

PMID- 24463931
TI  - Evolutionary aspects of elemental hyperaccumulation.
AB  - Hyperaccumulation is the uptake of one or more metal/metalloids to concentrations
      greater than 50-100* those of the surrounding vegetation or 100-10,000 mg/kg dry
      weight depending on the element. Hyperaccumulation has been documented in at
      least 515 taxa of angiosperms. By mapping the occurrence of hyperaccumulators
      onto the angiosperm phylogeny, we show hyperaccumulation has had multiple origins
      across the angiosperms. Even within a given order, family or genus, there are
      typically multiple origins of hyperaccumulation, either for the same or different
      elements. We address which selective pressures may have led to the evolution of
      hyperaccumulation and whether there is evidence for co-evolution with ecological
      partners. Considerable evidence supports the elemental-defense hypothesis, which
      states that hyperaccumulated elements protect the plants from herbivores and
      pathogens. There is also evidence that hyperaccumulation can result in drought
      stress protection, allelopathic effects or physiological benefits. In many
      instances, ecological partners of hyperaccumulators have evolved resistance to
      the hyperaccumulated element, indicating co-evolution. Studies on the molecular
      evolution of hyperaccumulation have pinpointed gene duplication as a common cause
      of increased metal transporter abundance. Hypertolerance to the hyperaccumulated
      element often relies upon chelating agents, such as organic acids (e.g., malate,
      citrate) or peptide/protein chelators that can facilitate transport and
      sequestration. We conclude the review with a summary and suggested future
      directions for hyperaccumulator research. 

PMID- 24463932
TI  - Effects of elevated CO2, warming and precipitation change on plant growth,
      photosynthesis and peroxidation in dominant species from North China grassland.
AB  - Warming, watering and elevated atmospheric CO2-concentration effects have been
      extensively studied separately; however, their combined impact on plants is not
      well understood. In the current research, we examined plant growth and
      physiological responses of three dominant species from the Eurasian Steppe with
      different functional traits to a combination of elevated CO2, high temperature,
      and four simulated precipitation patterns. Elevated CO2 stimulated plant growth
      by 10.8-41.7 % for a C3 leguminous shrub, Caragana microphylla, and by 33.2-52.3
      % for a C3 grass, Stipa grandis, across all temperature and watering treatments.
      Elevated CO2, however, did not affect plant biomass of a C4 grass, Cleistogenes
      squarrosa, under normal or increased precipitation, whereas a 20.0-69.7 %
      stimulation of growth occurred with elevated CO2 under drought conditions. Plant
      growth was enhanced in the C3 shrub and the C4 grass by warming under normal
      precipitation, but declined drastically with severe drought. The effects of
      elevated CO2 on leaf traits, biomass allocation and photosynthetic potential were
      remarkably species-dependent. Suppression of photosynthetic activity, and
      enhancement of cell peroxidation by a combination of warming and severe drought,
      were partly alleviated by elevated CO2. The relationships between plant
      functional traits and physiological activities and their responses to climate
      change were discussed. The present results suggested that the response to CO2
      enrichment may strongly depend on the response of specific species under varying
      patterns of precipitation, with or without warming, highlighting that individual
      species and multifactor dependencies must be considered in a projection of
      terrestrial ecosystem response to climatic change.

PMID- 24463933
TI  - Validation of metabolic syndrome score by confirmatory factor analysis in
      children and adults and prediction of cardiometabolic outcomes in adults.
AB  - AIMS/HYPOTHESIS: We validated the metabolic syndrome (MetS) score by confirmatory
      factor analysis (CFA) in children, middle-aged men, and older women and men and
      by investigating the relationships of the MetS score to incident type 2 diabetes,
      myocardial infarction, and cardiovascular and overall death in middle-aged men.
      METHODS: We assessed the core features of MetS, calculated the MetS score using z
      scores for waist circumference, insulin, glucose, triacylglycerols, HDL
      cholesterol and blood pressure, and carried out CFA to investigate whether MetS
      represents a single entity in population samples of 491 children, 1,900 middle
      aged men, 614 older women and 555 older men from Finland. We also followed-up
      incident type 2 diabetes for 11 years and other outcomes for 17-18 years in
      middle-aged men. RESULTS: We carried out second-order CFAs in which the MetS was
      represented by a second-order latent variable underlying four latent variables
      characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised
      blood pressure in different age groups. These second-order factors and factors
      derived from first-order CFA using previously proposed models were strongly
      associated with a composite MetS score in all age groups (r = 0.84-0.94) and
      similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in
      middle-aged men. The risk of type 2 diabetes, myocardial infarction,
      cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44
      fold, respectively, for a 1 SD increase in the MetS score. CONCLUSIONS: The MetS
      can be described as a single entity in all age groups. The MetS score is a valid
      tool for research evaluating cardiometabolic risk in different age groups.
      Further research is needed to define cut-off points for risk estimation in
      clinical practice.

PMID- 24463934
TI  - Infants use known verbs to learn novel nouns: evidence from 15- and 19-month
      olds.
AB  - Fluent speakers' representations of verbs include semantic knowledge about the
      nouns that can serve as their arguments. These "selectional restrictions" of a
      verb can in principle be recruited to learn the meaning of a novel noun. For
      example, the sentence He ate the carambola licenses the inference that carambola
      refers to something edible. We ask whether 15- and 19-month-old infants can
      recruit their nascent verb lexicon to identify the referents of novel nouns that
      appear as the verbs' subjects. We compared infants' interpretation of a novel
      noun (e.g., the dax) in two conditions: one in which dax is presented as the
      subject of animate-selecting construction (e.g., The dax is crying), and the
      other in which dax is the subject of an animacy-neutral construction (e.g., The
      dax is right here). Results indicate that by 19months, infants use their
      representations of known verbs to inform the meaning of a novel noun that appears
      as its argument. 

PMID- 24463935
TI  - Endothelin receptor blockade ameliorates renal injury by inhibition of RhoA/Rho
      kinase signalling in deoxycorticosterone acetate-salt hypertensive rats.
AB  - PURPOSE OF REVIEW: Excessive production of fibrosis is a feature of hypertension
      induced renal injury. Activation of RhoA/Rho-kinase (ROCK) axis has been shown in
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We assessed whether
      selective endothelin receptor blockers can attenuate renal fibrosis by inhibiting
      RhoA/ROCK axis in DOCA-salt rats. METHODS: At 4 weeks after the start of DOCA
      salt treatment and uninephrectomization, male Wistar rats were randomized into
      three groups for 4 weeks: vehicle, ABT-627 (endothelin-A receptor inhibitor) and
      A192621 (endothelin-B receptor inhibitor). RESULTS: DOCA-salt was characterized
      by increased blood pressure, decreased renal function, increased proteinuria,
      increased glomerulosclerosis and tubulointerstitial fibrosis with myofibroblast
      accumulation, increased renal endothelin-1 levels and RhoA activity along with
      increased expression of connective tissue growth factor at both mRNA and protein
      levels as compared with uninephrectomized control male Wistar rats. Treatment
      with a selective mineralocorticoid receptor antagonist, eplerenone, ameliorated
      proteinuria. Impaired renal function and histological changes were overcome by
      treatment with ABT-627, but not with A192621. The beneficial effects of bosentan,
      a nonspecific endothelin receptor blocker, on proteinuria, RhoA activity, and
      connective tissue growth factor levels were similar to ABT-627. Furthermore, in
      an isolated perfuse kidney, a RhoA inhibitor, C3 exoenzyme, and two ROCK
      inhibitors, fasudil and Y-27632, significantly attenuated connective tissue
      growth factor levels. CONCLUSIONS: These results indicate that DOCA-salt elevates
      renal endothelin-1 levels and RhoA activity via activation of mineralocorticoid
      receptor, resulting in renal fibrosis and proteinuria. Endothelin-A receptor
      blockade can attenuate DOCA-salt-induced renal fibrosis probably through the
      inhibition of RhoA/ROCK activity and connective tissue growth factor expression.

PMID- 24463936
TI  - Methodological quality of meta-analyses on the blood pressure response to
      exercise: a review.
AB  - Numerous meta-analyses have been conducted to summarize the growing numbers of
      trials addressing the effects of exercise on blood pressure (BP), yet it is
      unclear how well they have satisfied contemporary methodological standards. We
      applied an augmented version of the Assessment of Multiple Systematic Reviews
      (AMSTARExBP) scale to 33 meta-analyses retrieved from searches of electronic
      databases. Qualifying reports used meta-analytic procedures; examined controlled
      exercise training trials; had BP as a primary outcome; and had exercise or
      physical activity interventions independently or combined with other lifestyle
      interventions. AMSTARExBP scores averaged near the middle of the scale (Mean =
      56.0% +/- 21.4% of total items possible); co-authored and more recent meta
      analyses had higher quality scores. Common deficits were failures to disclose
      full search details (30% did), gauge the quality of included trials (48% did),
      use duplicate study selection and data extraction (55% did), or incorporate study
      quality in formulating results (35% did). Nearly all (91%) meta-analyses observed
      that exercise significantly lowered BP; fewer (58%) found that such effects
      depended on exercise or patient characteristics but these patterns often
      conflicted. Meta-analyses are often pillars of clinical recommendations and
      guidelines, yet only 58% addressed the clinical translations of their findings.
      In sum, meta-analyses have contributed less than ideally to our understanding of
      how exercise may impact BP, or how these BP effects may be moderated by patient
      or exercise characteristics. Future meta-analyses that better satisfy
      contemporary standards offer considerable promise to understand how and for whom
      exercise impacts BP. 

PMID- 24463938
TI  - Erythropoietin-induced hypertension and vascular injury in mice overexpressing
      human endothelin-1: exercise attenuated hypertension, oxidative stress,
      inflammation and immune response.
AB  - OBJECTIVE: Erythropoietin used to correct anaemia in chronic kidney disease (CKD)
      has been shown to increase blood pressure (BP) in CKD patients and experimental
      animals. Endothelin (ET)-1 expression is increased in CKD animals and patients,
      and enhanced by erythropoietin. Erythropoietin-induced BP rise was blunted by ETA
      receptor blockers. This study was designed to determine whether preexisting
      endothelin (ET)-1 overexpression is required for erythropoietin to cause adverse
      vascular effects and whether this could be prevented by exercise training.
      METHODS: Eight to 10-week old male wild-type mice and mice with endothelial
      specific ET-1 overexpression (eET-1) were treated or not with EPO (100  IU/kg,
      SC, 3  times/week). eET-1 was subjected or not to swimming exercise training (1 
      h/day, 6 days/week) for 8 weeks. SBP, mesenteric artery endothelial function and
      remodelling, NADPH oxidase activity, reactive oxygen species (ROS) generation,
      vascular cell adhesion protein (VCAM)-1, monocyte/macrophage infiltration, T
      regulatory cells (Tregs) and tissue ET-1 and plasma endothelin were determined.
      RESULTS: Erythropoietin increased SBP by 24  mmHg (P < 0.05) and decreased by 25%
      vasodilatory responses to acetylcholine (P < 0.01) in eET-1 mice. Erythropoietin
      enhanced ET-1 induced increase in resistance artery media/lumen ratio (31%, P <
      0.05), aortic NADPH oxidase activity (50%, P < 0.05), ROS generation (93%, P <
      0.001), VCAM-1 (80%, P < 0.01) and monocyte/macrophage infiltration (159%, P <
      0.001), and raised plasma and aortic ET-1 levels (>=130%, P < 0.05). EPO had no
      effect in wild-type mice. Exercise training prevented all of the above (P <
      0.05). CONCLUSION: Erythropoietin-induced adverse vascular effects are dependent
      on preexisting elevated ET-1 expression. Exercise training prevented
      erythropoietin-induced adverse vascular effects in part by inhibiting ET-1
      overexpression-induced oxidative stress, inflammation and immune activation.

PMID- 24463939
TI  - A new approach to glycan targeting: enzyme inhibition by oligosaccharide
      metalloshielding.
AB  - Metalloglycomics - the effects of defined coordination compounds on
      oligosaccharides and their structure and function - opens new areas for
      bioinorganic chemistry and expands its systematic study to the third major class
      of biomolecules after DNA/RNA and proteins. 

PMID- 24463937
TI  - Angiotensin-(1-9) reverses experimental hypertension and cardiovascular damage by
      inhibition of the angiotensin converting enzyme/Ang II axis.
AB  - BACKGROUND: Little is known about the biological effects of angiotensin-(1-9),
      but available evidence shows that angiotensin-(1-9) has beneficial effects in
      preventing/ameliorating cardiovascular remodeling. OBJECTIVE: In this study, we
      evaluated whether angiotensin-(1-9) decreases hypertension and reverses
      experimental cardiovascular damage in the rat. METHODS AND RESULTS: Angiotensin
      (1-9) (600  ng/kg per min for 2 weeks) reduced already-established hypertension
      in rats with early high blood pressure induced by angiotensin II infusion or
      renal artery clipping. Angiotensin-(1-9) also improved cardiac (assessed by
      echocardiography) and endothelial function in small-diameter mesenteric arteries,
      cardiac and aortic wall hypertrophy, fibrosis, oxidative stress, collagen and
      transforming growth factor type beta - 1 protein expression (assessed by western
      blot). The beneficial effect of angiotensin-(1-9) was blunted by coadministration
      of the angiotensin type 2(AT2) receptor blocker PD123319 (36  ng/kg per min) but
      not by coadministration of the Mas receptor blocker A779 (100  ng/kg per min).
      Angiotensin-(1-9) treatment also decreased circulating levels of Ang II,
      angiotensin-converting enzyme activity and oxidative stress in aorta and left
      ventricle. Whereas, Ang-(1-9) increased endothelial nitric oxide synthase mRNA
      levels in aorta as well as plasma nitrate levels. CONCLUSION: Angiotensin-(1-9)
      reduces hypertension, ameliorates structural alterations (hypertrophy and
      fibrosis), oxidative stress in the heart and aorta and improves cardiac and
      endothelial function in hypertensive rats. These effects were mediated by the AT2
      receptor but not by the angiotensin-(1-7)/Mas receptor axis.

PMID- 24463940
TI  - A lab-on-chip cell-based biosensor for label-free sensing of water toxicants.
AB  - This paper presents a lab-on-chip biosensor containing an enclosed fluidic cell
      culturing well seeded with live cells for rapid screening of toxicants in
      drinking water. The sensor is based on the innovative placement of the working
      electrode for the electrical cell-substrate impedance sensing (ECIS) technique as
      the top electrode of a quartz crystal microbalance (QCM) resonator. Cell damage
      induced by toxic water will cause a decrease in impedance, as well as an increase
      in the resonant frequency. For water toxicity tests, the biosensor's unique
      capabilities of performing two complementary measurements simultaneously
      (impedance and mass-sensing) will increase the accuracy of detection while
      decreasing the false-positive rate. Bovine aortic endothelial cells (BAECs) were
      used as toxicity sensing cells. The effects of the toxicants, ammonia, nicotine
      and aldicarb, on cells were monitored with both the QCM and the ECIS technique.
      The lab-on-chip was demonstrated to be sensitive to low concentrations of
      toxicants. The responses of BAECs to toxic samples occurred during the initial 5
      to 20 minutes depending on the type of chemical and concentrations. Testing the
      multiparameter biosensor with aldicarb also demonstrated the hypothesis that
      using two different sensors to monitor the same cell monolayer provides cross
      validation and increases the accuracy of detection. For low concentrations of
      aldicarb, the variations in impedance measurements are insignificant in
      comparison with the shifts of resonant frequency monitored using the QCM
      resonator. A highly linear correlation between signal shifts and chemical
      concentrations was demonstrated for each toxicant. 

PMID- 24463942
TI  - Indolent pneumonia in a pregnant recent immigrant from Ethiopia: think TB.
AB  - Time delay to tuberculosis (TB) diagnosis remains a public health concern. In
      pregnancy, early TB diagnosis is challenging and acquires further significance
      due to the risk of infection of the newborn as well as others in the maternity
      setting. We report a delay of 12 weeks in the diagnosis of TB in a pregnant
      recent immigrant from Ethiopia to Israel. Contact investigation revealed
      pulmonary TB in her two daughters aged four and seven years. We discuss the
      reasons for this delay in diagnosis, how a more timely diagnosis might have been
      made, and the dilemma of initiating treatment in unconfirmed TB. 

PMID- 24463941
TI  - Maternal and hospital characteristics of non-medically indicated deliveries prior
      to 39 weeks.
AB  - Non-medically indicated (NMI) deliveries prior to 39 weeks increase the risk of
      neonatal mortality, excess morbidity, and health care costs. The study's purpose
      was to identify maternal and hospital characteristics associated with NMI
      deliveries prior to 39 weeks. The study included 207,775 births to women without
      a previous cesarean and 38,316 births to women with a previous cesarean, using
      data from Florida's 2006-2007 linked birth certificate and inpatient record file.
      Adjusted risk ratios (ARR) and 95 % confidence intervals (CI) for characteristics
      were calculated using generalized estimating equation for multinomial logistic
      regression. Among women without a previous cesarean, NMI deliveries occurred in
      18,368 births (8.8 %). Non-medically indicated inductions were more likely in
      women who were non-Hispanic white (ARR: 1.41, 95 % CI 1.31-1.52), privately
      insured (ARR: 1.42, 95 % CI 1.26-1.59), and delivered in hospitals with <500
      births per year. Non-medically indicated primary cesareans were more likely in
      women who were older than 35 years (ARR: 2.96, 95 % CI 2.51-3.50), non-Hispanic
      white (ARR: 1.44, 95 % CI 1.30-1.59), and privately-insured (ARR: 1.43, 95 % CI
      1.17-1.73). Non-medically indicated primary cesareans were also more likely to
      occur in hospitals with <30 % nurse-midwife births, <500 births per year, and in
      large metro areas. Among women with previous cesarean, NMI repeat cesareans
      occurred in 16,746 births (43.7 %). Only weak risk factors were identified for
      NMI repeat cesareans. The risk factors identified varied by NMI outcome. This
      information can be used to inform educational campaigns and identify hospitals
      that may benefit from quality improvement efforts.

PMID- 24463943
TI  - A pilot study of transcranial Doppler-guided initial resuscitation of traumatic
      and non-traumatic comatose patients.
AB  - BACKGROUND: The aim of this study was to evaluate the usefulness of early
      Transcranial Doppler (TCD) in guiding initial resuscitation of traumatic and non
      traumatic comatose patients before diagnostic imaging and invasive neurologic
      monitoring. METHODS: This was a prospective, interventional study and included
      patients in coma, before performing diagnostic imaging. A TCD was performed as
      soon as possible upon admission. Diastolic velocity (DV) <20 cm/s and Pulsatility
      Index (PI) >1.4 at both middle cerebral arteries were considered abnormal and
      specific therapy was started with fluid expansion with 2 L 0.9% saline solution,
      followed by norepinephrine infusion to increase MAP above 110 mmHg. An increment
      in DV >20 cm/s was considered as a good response. RESULTS: Twenty-eight patients
      were included, 9 had normal TCD and 19 (68%) had abnormal TCD values. Mean values
      pre- and post-treatment were: MAP 84 +/- 16/121 +/- 9 mmHg; PI 2.26 +/- 0.52/1.28
      +/- 0.47; DV 13 +/- 7/33 +/- 18 cm/s (P<0.0001 for all values); 13 patients (68%)
      were responders. Global mortality was 46 %. We find that the presence of
      oscillating flow, systolic peak or DV <20 cm/s after treatment, were associated
      with brain death in 100% of cases. Presence of a normal TCD was associated with
      no mortality. CONCLUSION: Our study suggests that early TCD is feasible to
      evaluate qualitative information about cerebral perfusion in comatose patients
      while they are waiting for diagnostic imaging studies.

PMID- 24463944
TI  - Computed tomography angiography: a double step methodology in brain death
      confirmation.

PMID- 24463945
TI  - Reversing severe dilutional coagulopathy: towards appropriate management and one
      more nail in the starches' coffin.

PMID- 24463946
TI  - Designing quantum dots for solotronics.
AB  - Solotronics, optoelectronics based on solitary dopants, is an emerging field of
      research and technology reaching the ultimate limit of miniaturization. It aims
      at exploiting quantum properties of individual ions or defects embedded in a
      semiconductor matrix. It has already been shown that optical control of a
      magnetic ion spin is feasible using the carriers confined in a quantum dot.
      However, a serious obstacle was the quenching of the exciton luminescence by
      magnetic impurities. Here we show, by photoluminescence studies on thus-far
      unexplored individual CdTe dots with a single cobalt ion and CdSe dots with a
      single manganese ion, that even if energetically allowed, nonradiative exciton
      recombination through single-magnetic-ion intra-ionic transitions is negligible
      in such zero-dimensional structures. This opens solotronics for a wide range of
      as yet unconsidered systems. On the basis of results of our single-spin
      relaxation experiments and on the material trends, we identify optimal magnetic
      ion quantum dot systems for implementation of a single-ion-based spin memory. 

PMID- 24463947
TI  - Access to treatment for toddlers with autism spectrum disorders.
AB  - New research shows that intensive and early intervention (EI) has the potential
      to change brain function in young children with Autism Spectrum Disorders (ASD).
      Despite the positive benefit of EI, many families (n = 16) reported difficulties
      accessing EI services following an ASD diagnosis at the intensity viewed
      necessary for optimal child outcome. Parents reported that on average they
      secured 6.81 hours of services per month and that limited access to EI services
      led to increased parental stress at a time when a new ASD diagnosis was often
      overwhelming. Findings are discussed in terms of support to families who are
      experiencing difficulties accessing care after new ASD diagnosis. 

PMID- 24463948
TI  - Anticipatory guidance through DVD.
AB  - The major purpose of the study was to determine if a 5-minute DVD is an effective
      method for communicating anticipatory guidance to parents at their child's 4
      month well-child visit. A total of 84 caregivers were randomly assigned to
      receive anticipatory guidance through standard care (written anticipatory
      guidance handout and free talk) or DVD (DVD format + standard care). Participants
      completed a brief questionnaire immediately before and after their visit. As
      anticipated, knowledge scores improved significantly from pre-test to post-test.
      There was also a significant interaction between format used for anticipatory
      guidance and time. Specifically, there was greater improvement in knowledge over
      time for parents in the DVD group as compared with the standard care group.
      Additionally, the mean knowledge level of those in the DVD group as compared with
      those in the standard care group trended toward significance. Finally, visit
      length was shortened by nearly 3 minutes in the DVD group, and close to 100% of
      all respondents, regardless of anticipatory guidance format, indicated that they
      were very satisfied with their visit and amount of information learned. 

PMID- 24463949
TI  - An 8-year-old male with 4 days of fever, abdominal pain, and jaundice.

PMID- 24463950
TI  - Treatment variability of asthma exacerbations in a pediatric emergency department
      using a severity-based management protocol.

PMID- 24463952
TI  - Revisiting the classification of curtoviruses based on genome-wide pairwise
      identity.
AB  - Members of the genus Curtovirus (family Geminiviridae) are important pathogens of
      many wild and cultivated plant species. Until recently, relatively few full
      curtovirus genomes have been characterised. However, with the 19 full genome
      sequences now available in public databases, we revisit the proposed curtovirus
      species and strain classification criteria. Using pairwise identities coupled
      with phylogenetic evidence, revised species and strain demarcation guidelines
      have been instituted. Specifically, we have established 77 % genome-wide pairwise
      identity as a species demarcation threshold and 94 % genome-wide pairwise
      identity as a strain demarcation threshold. Hence, whereas curtovirus sequences
      with >77 % genome-wide pairwise identity would be classified as belonging to the
      same species, those sharing >94 % identity would be classified as belonging to
      the same strain. We provide step-by-step guidelines to facilitate the
      classification of newly discovered curtovirus full genome sequences and a set of
      defined criteria for naming new species and strains. The revision yields three
      curtovirus species: Beet curly top virus (BCTV), Spinach severe surly top virus
      (SpSCTV) and Horseradish curly top virus (HrCTV).

PMID- 24463951
TI  - Delay and refusal of human papillomavirus vaccine for girls, national
      immunization survey-teen, 2010.
AB  - Human papillomavirus (HPV) vaccine coverage among girls is low. We used data
      reported by parents of 4103 girls, 13 to 17 years old, to assess associations
      with, and reasons for, delaying or refusing HPV vaccination. Sixty-nine percent
      of parents neither delayed nor refused vaccination, 11% delayed only, 17% refused
      only, and 3% both delayed and refused. Eighty-three percent of girls who delayed
      only, 19% who refused only, and 46% who both delayed and refused went on to
      initiate the vaccine series or intended to initiate it within the next 12 months.
      A significantly higher proportion of parents of girls who were non-Hispanic
      white, lived in households with higher incomes, and had mothers with higher
      education levels, delayed and/or refused vaccination. The most common reasons for
      nonvaccination were concerns about lasting health problems from the vaccine,
      wondering about the vaccine's effectiveness, and believing the vaccine is not
      needed. 

PMID- 24463953
TI  - High-resolution melting analysis for mutation scanning in the non-coding control
      region of JC polyomavirus from patients with progressive multifocal
      leukoencephalopathy.
AB  - JC polyomavirus (JCV) is the causative agent of progressive multifocal
      leukoencephalopathy (PML), a fatal demyelinating disease. JCV isolates from PML
      patients have hypervariable mutations in the noncoding control region (NCCR) of
      the viral genome. Although nucleotide sequencing analysis of NCCR mutation is
      useful for the confirmation of PML diagnosis and basic studies examining JCV
      variants, it is often labor-intensive, time-consuming, and expensive. This study
      was conducted to evaluate the feasibility of a high-resolution melting (HRM)
      analysis technique for the rapid and low-cost scanning of NCCR mutations. The
      real-time PCR-HRM assay was developed with a pair of primers targeting the NCCR,
      and mutational patterns of NCCRs were compared using sequence-confirmed JCV DNA
      clones and CSF DNAs from PML patients. The NCCR patterns of DNA clones of the
      archetype JCV and PML-type variants could be differentiated by PCR-HRM. The
      mutational patterns of the rearranged NCCR clones were similar to those of JCV
      variants in the original CSF specimens as judged by nested PCR-HRM using pre
      amplified targets. In addition, nested PCR-HRM could distinguish NCCR mutations
      in the JCV DNAs from each specimen at the patient level. These results indicate
      that the HRM-based assay affords a valuable technique for PML diagnosis and a
      versatile tool for the rapid scanning of NCCR mutations. 

PMID- 24463954
TI  - Complete genome sequence of Jacquemontia yellow mosaic virus, a novel begomovirus
      from Venezuela related to other New World bipartite begomoviruses infecting
      Convolvulaceae.
AB  - The complete genome of a bipartite begomovirus (genus Begomovirus, family
      Geminiviridae) infecting Jacquemontia sp. (Convolvulaceae) in Venezuela has been
      cloned and sequenced. Sequence comparison and phylogenetic analysis have shown
      that it represents an isolate of a novel species with closest relatives being two
      New World bipartite begomoviruses that infect Convolvulaceae, Jacquemontia mosaic
      Yucatan virus and Merremia mosaic virus. The DNA-As of these begomoviruses,
      however, share only 77.0-78.4 % nucleotide sequence identity with the DNA-A of
      the isolate described here, for which a recombinant origin is suggested. Based on
      the symptoms observed in the field, the name Jacquemontia yellow mosaic virus
      (JacYMV) is proposed for this novel bipartite begomovirus.

PMID- 24463955
TI  - Alpha-Fe(2)O(3) elicits diameter-dependent effects during exposure to an in vitro
      model of the human placenta.
AB  - Iron oxide nanoparticles offer unique possibilities due to the change in their
      physico-chemical parameters when synthesized on the nanoscale (10(-9) m) compared
      to their bulk forms. While novel uses exist for these materials when synthesized
      as nanoparticles, their unintended effects on the human body and specifically
      during pregnancy remain ill defined. In this study, an iron oxide nanoparticle,
      alpha-Fe2O3, was employed and the potential toxicity due to exposure was assessed
      in the widely used model human placental cell line BeWo b30. These cells were
      grown as epithelia, and subsequently assessed for their epithelial integrity,
      reactive oxygen species production and cellular viability, ultrastructural and
      morphological disruption, and genotoxicity as a result of exposure to alpha-Fe2O3
      nanoparticles. Transepithelial electrical resistance indicated that exposure to
      the large (50 and 78 nm), but not small (15 nm) diameter particles of alpha-Fe2O3
      nanomaterial resulted in leakiness of the epithelium. Exposure to the large
      diameters of 50 and 78 nm resulted in increases in cell death and reactive oxygen
      species. Disruption of junctional integrity as monitored by immunolocalization of
      the tight junction protein ZO-1 was found to occur as a consequence of exposure
      to large diameter NPs. It was found that there was reduction in the number of
      microvilli responsible for increased surface area for nutrient absorption after
      exposing the epithelia to large diameter NPs. Finally, genotoxicity as assessed
      by DNA microarray and confirmed by QPCR indicated that the large diameter
      particles (78 nm) induce apoptosis in these cells. These data indicate that large
      (50 and 78 nm), but not small (15 nm) alpha-Fe2O3 nanoparticles disrupt the
      barrier function of this epithelium as assessed by in vitro analysis.

PMID- 24463956
TI  - Chip-integrated ultrawide-band all-optical logic comparator in plasmonic
      circuits.
AB  - Optical computing opens up the possibility for the realization of ultrahigh-speed
      and ultrawide-band information processing. Integrated all-optical logic
      comparator is one of the indispensable core components of optical computing
      systems. Unfortunately, up to now, no any nanoscale all-optical logic comparator
      suitable for on-chip integration applications has been realized experimentally.
      Here, we report a subtle and effective technical solution to circumvent the
      obstacles of inherent Ohmic losses of metal and limited propagation length of
      SPPs. A nanoscale all-optical logic comparator suitable for on-chip integration
      applications is realized in plasmonic circuits directly. The incident single-bit
      (or dual-bit) logic signals can be compared and the comparison results are
      endowed with different logic encodings. An ultrabroad operating wavelength range
      from 700 to 1000 nm, and an ultrahigh output logic-state contrast-ratio of more
      than 25 dB are realized experimentally. No high power requirement is needed.
      Though nanoscale SPP light source and the logic comparator device are integrated
      into the same plasmonic chip, an ultrasmall feature size is maintained. This work
      not only paves a way for the realization of complex logic device such as adders
      and multiplier, but also opens up the possibility for realizing quantum solid
      chips based on plasmonic circuits.

PMID- 24463957
TI  - Mammary-type myofibroblastoma of the liver: multi-modality imaging features with
      histopathologic correlation.
AB  - A 46-year-old woman with an incidentally discovered hepatic mass at the time of
      echocardiography underwent additional imaging for characterization. Ultrasound
      demonstrated a 5.3 cm solid hyperechoic mass. Computed tomography and magnetic
      resonance imaging showed intratumoral fat and nodular foci of progressive
      enhancement. The patient underwent surgical resection, with the mass
      demonstrating histopathologic and immunohistochemical features diagnostic of a
      hepatic mammary-type myofibroblastoma. We present herein the clinical, imaging,
      and pathologic features in this unique case of hepatic mammary-type
      myofibroblastoma. Mammary-type myofibroblastoma is a benign spindle cell tumor
      typically composed of groups of myofibroblasts within bands of hyalinized
      collagenous stroma. Some tumors also have an adipocytic component. The tumor is
      nearly exclusively seen in the breast and although extramammary soft tissue
      locations have been described, to our knowledge, this is the first reported case
      in the liver or any visceral site. Although rare, radiologists and clinicians
      should, therefore, be aware of the possibility of a mammary-type myofibroblastoma
      when a solid, non-encapsulated, fat containing tumor in the liver is encountered.

PMID- 24463958
TI  - Psychometric properties of a short self-reported measure of medication adherence
      among patients with hypertension treated in a busy clinical setting in Korea.
AB  - BACKGROUND: We examined the psychometric properties of the Korean version of the
      8-item Morisky Medication Adherence Scale (MMAS-8) among adults with
      hypertension. METHODS: A total of 373 adults with hypertension were given face-to
      face interviews in 2 cardiology clinics at 2 large teaching hospitals in Seoul,
      South Korea. Blood pressure was measured twice, and medical records were
      reviewed. About one-third of the participants (n = 109) were randomly selected
      for a 2-week test-retest evaluation of reliability via telephone interview.
      RESULTS: Internal consistency reliability was moderate (Cronbach alpha = 0.56),
      and test-retest reliability was excellent (intraclass correlation = 0.91; P <
      0.001), although a ceiling effect was detected. The correlation of MMAS-8 scores
      with scores for the original 4-item scale indicated that convergent validity was
      good (r = 0.92; P < 0.01). A low MMAS-8 score was significantly associated with
      poor blood pressure control (chi(2) = 29.86; P < 0.001; adjusted odds ratio =
      5.08; 95% CI, 2.56-10.08). Using a cut-off point of 6, sensitivity and
      specificity were 64.3% and 72.9%, respectively. Exploratory factor analysis
      identified 3 dimensions of the scale, with poor fit for the 1-dimensional
      construct using confirmatory factory analysis. CONCLUSIONS: The MMAS-8 had
      satisfactory reliability and validity and thus might be suitable for assessment
      and counseling regarding medication adherence among adults with hypertension in a
      busy clinical setting in Korea.

PMID- 24463959
TI  - Characteristics of sudden unexpected cancer deaths investigated by medical
      examiners in Tokyo, Japan (2009).
AB  - BACKGROUND: Annually, about 400 cases of sudden unexpected death are attributed
      to cancer in Tokyo, Japan. These individuals may have been undiagnosed, or their
      medical conditions may not have been carefully evaluated before death. We
      examined medical consultations, cancer diagnoses, and economic status of all
      cancer deaths investigated by medical examiners in 2009. METHODS: Among cases
      handled by the Tokyo Medical Examiner's Office in 2009 (N = 12 493), records for
      all cases of cancer death (n = 400) were reviewed to determine the extent of
      medical care provided, diagnosis before death, and economic status of the
      decedent. RESULTS: Most of the decedents (n = 232; 58%) had received a diagnosis
      of terminal/advanced cancer during a medical consultation. Most did not receive
      such medical consultations at home, despite their very weak physical condition.
      However, nearly one quarter of decedents (24%; 95/400) had not received a cancer
      diagnosis before death. The proportions of decedents who had been indigent,
      received no medical consulting, and had colon cancer were significantly higher
      among undiagnosed cases than among diagnosed cases. Indigent persons were the
      largest subgroup (n = 19; 43%) among those who had never received a medical
      consultation (n = 44). In addition, the proportion of those who had discontinued
      or received no medical consultation was higher among indigent persons than among
      non-indigent persons. CONCLUSIONS: The quality of medical services for cancer
      patients could be improved by educating general practitioners about terminal
      care, expanding efforts to monitor and diagnose cancer, especially among indigent
      patients, and increasing participation rates for colorectal cancer screening.

PMID- 24463960
TI  - Release mechanism and parameter estimation in drug-eluting stent systems:
      analytical solutions of drug release and tissue transport.
AB  - Drug-eluting stents have significantly improved the treatment of coronary artery
      disease. They offer reduced rates of restenosis compared with their bare-metal
      predecessors and are the current gold standard in percutaneous coronary
      interventions. Drug-eluting stents have been approved for use in humans since
      2002 and yet, despite the intensive research activity over the past decade, the
      drug release mechanism(s) and the uptake into the arterial wall are still poorly
      understood. While stent manufacturers have focussed primarily on empirical
      methods, several mathematical models have appeared in the literature considering
      the release problem, the uptake problem and also the coupled problem. However,
      two significant challenges that remain are in understanding the drug release
      mechanism(s) and also the determination of the various parameters characterizing
      the system. These include drug diffusion coefficients and dissolution constants
      in the stent polymer coating as well as drug diffusion coefficients,
      binding/uptake rates and the magnitude of the transmural convection in the
      arterial wall. In this paper we attempt to address these problems. We provide
      analytical solutions which, when compared with appropriate experiments, may allow
      the various parameters of the system to be estimated via the inverse problem. The
      analytical solutions which we provide here for drug release in vitro may thus be
      used as a tool for providing insights into the mechanism(s) of release. 

PMID- 24463961
TI  - Sphingosine-1-phosphate induces differentiation of cultured renal tubular
      epithelial cells under Rho kinase activation via the S1P2 receptor.
AB  - BACKGROUND: Sphingosine-1-phosphate (S1P) is reportedly involved in the
      pathogenesis of kidney disease; however, the precise role played by S1P in renal
      disorders still remains controversial. Rho kinase plays an important role in the
      development of diabetic nephropathy by inducing glomerular and tubulointerstitial
      fibrosis. Rho kinase is known to be stimulated by S1P through its specific
      receptor, S1P2 receptor (S1P2). Hence, we investigated whether S1P-S1P2 signaling
      plays a role in the epithelial-mesenchymal transition (EMT) through Rho kinase
      activation in renal tubules. METHOD: To characterize the distribution of the
      S1P2, an immunohistochemical examination of the receptor was performed in the
      kidney of the non-diabetic and diabetic mice. Next, we examined Rho kinase
      activity as well as E-cadherin and alpha-smooth muscle actin (alpha-SMA)
      expression by real-time RT-PCR and western blotting in cultured rat tubular
      epithelial cells under S1P stimulation with and without a Rho kinase inhibitor
      and an S1P2 blocker. In addition, the distribution of E-cadherin and alpha-SMA
      was examined by immunocytochemistry. RESULT: S1P2 was expressed mainly in the
      renal tubules; expression was intense in collecting ducts and distal tubules
      compared to other segments. S1P induced activation of Rho kinase through the
      S1P2, which changed the distribution of E-cadherin and increased the expression
      of alpha-SMA. CONCLUSION: Rho kinase activation by S1P via S1P2 initiated EMT
      changes in cultured renal tubular cells. Our results suggest that excessive
      stimulation of S1P might facilitate renal fibrosis via activation of Rho kinase
      through S1P2.

PMID- 24463962
TI  - Alternative human liver transcripts of TCF7L2 bind to the gluconeogenesis
      regulator HNF4alpha at the protein level.
AB  - AIMS/HYPOTHESIS: Gene polymorphisms of TCF7L2 are associated with increased risk
      of type 2 diabetes and transcription factor 7-like 2 (TCF7L2) plays a role in
      hepatic glucose metabolism. We therefore addressed the impact of TCF7L2 isoforms
      on hepatocyte nuclear factor 4alpha (HNF4alpha) and the regulation of
      gluconeogenesis genes. METHODS: Liver TCF7L2 transcripts were analysed by
      quantitative PCR in 33 non-diabetic and 31 type 2 diabetic obese individuals
      genotyped for TCF7L2 rs7903146. To analyse transcriptional regulation by TCF7L2,
      small interfering RNA transfection, luciferase reporter and co
      immunoprecipitation assays were performed in human hepatoma HepG2 cells. RESULTS:
      In livers of diabetic compared with normoglycaemic individuals, five C-terminal
      TCF7L2 transcripts showed increased expression. The type 2 diabetes risk allele
      of rs7903146 positively correlated with TCF7L2 expression in livers from
      normoglycaemic individuals only. In HepG2 cells, transcript and TCF7L2 protein
      levels were increased upon incubation in high glucose and insulin. Of the exon 13
      transcripts, six were increased in a glucose dose-responsive manner. TCF7L2
      transcriptionally regulated 29 genes related to glucose metabolism, including
      glucose-6-phosphatase. In cultured HepG2 cells, TCF7L2 did not regulate HNF4Alpha
      and FOXO1 transcription, but did affect HNF4alpha protein expression. The TCF7L2
      isoforms T6 and T8 (without exon 13 and with exon 15/14, respectively)
      specifically interacted with HNF4alpha. CONCLUSIONS/INTERPRETATION: The different
      levels of expression of alternative C-terminal TCF7L2 transcripts in HepG2 cells,
      in livers of normoglycaemic individuals carrying the rs7901346 type 2 diabetes
      risk allele and in livers of diabetic individuals suggest that these transcripts
      play a role in the pathophysiology of type 2 diabetes. We also report for the
      first time a protein interaction in HepG2 cells between HNF4alpha and the T6 and
      T8 isoforms of TCF7L2, which suggests a distinct role for these specific
      alternative transcripts.

PMID- 24463963
TI  - Detection of free fatty acid receptor 1 expression: the critical role of negative
      and positive controls.
AB  - AIMS/HYPOTHESIS: Adequate evaluation of protein expression is a crucial
      prerequisite for functional studies. Commonly used strategies comprise detection
      of proteins by specific antibodies using western blotting and immunohistochemical
      staining, or detection of mRNA by in situ hybridisation and RT-PCR. We evaluated
      the tools for the detection of free fatty acid receptor 1 (FFAR1) expression.
      METHODS: Commercially available antibody preparations were used to detect
      endogenous expression of the FFAR1 receptor and this was compared with cell
      preparations deficient or overexpressing the mouse or human receptor.
      Concentrations of mRNA were evaluated by RT-PCR. RESULTS: All insulin-secreting
      cells, INS-1E, Min6 and mouse islets showed specific expression of Ffar1 at the
      mRNA level. However, none of the commercially available antibodies specifically
      detected rat, mouse or human FFAR1. CONCLUSIONS/INTERPRETATION: Proper positive
      and negative controls are an important prerequisite for the evaluation of FFAR1
      expression.

PMID- 24463964
TI  - A link between arabinose utilization and oxalotrophy in Bradyrhizobium japonicum.
AB  - Rhizobia have a versatile catabolism that allows them to compete successfully
      with other microorganisms for nutrients in the soil and in the rhizosphere of
      their respective host plants. In this study, Bradyrhizobium japonicum USDA 110
      was found to be able to utilize oxalate as the sole carbon source. A proteome
      analysis of cells grown in minimal medium containing arabinose suggested that
      oxalate oxidation extends the arabinose degradation branch via glycolaldehyde. A
      mutant of the key pathway genes oxc (for oxalyl-coenzyme A decarboxylase) and frc
      (for formyl-coenzyme A transferase) was constructed and shown to be (i) impaired
      in growth on arabinose and (ii) unable to grow on oxalate. Oxalate was detected
      in roots and, at elevated levels, in root nodules of four different B. japonicum
      host plants. Mixed-inoculation experiments with wild-type and oxc-frc mutant
      cells revealed that oxalotrophy might be a beneficial trait of B. japonicum at
      some stage during legume root nodule colonization. 

PMID- 24463965
TI  - Refined NrfA phylogeny improves PCR-based nrfA gene detection.
AB  - Dissimilatory nitrate reduction to ammonium (DNRA) and denitrification are
      contrasting microbial processes in the terrestrial nitrogen (N) cycle, in that
      the former promotes N retention and the latter leads to N loss (i.e., the
      formation of gaseous products). The nitrite reductase NrfA catalyzes nitrite
      reduction to ammonium, the enzyme associated with respiratory nitrite
      ammonification and the key step in DNRA. Although well studied biochemically, the
      diversity and phylogeny of this enzyme had not been rigorously analyzed. A
      phylogenetic analysis of 272 full-length NrfA protein sequences distinguished 18
      NrfA clades with robust statistical support (>90% Bayesian posterior
      probabilities). Three clades possessed a CXXCH motif in the first heme-binding
      domain, whereas all other clades had a CXXCK motif in this location. The analysis
      further identified a KXRH or KXQH motif between the third and fourth heme-binding
      motifs as a conserved and diagnostic feature of all pentaheme NrfA proteins. PCR
      primers targeting a portion of the heme-binding motifs that flank this diagnostic
      region yielded the expected 250-bp-long amplicons with template DNA from eight
      pure cultures and 16 new nrfA-containing isolates. nrfA amplicons obtained with
      template DNA from two geomorphically distinct agricultural soils could be
      assigned to one of the 18 NrfA clades, providing support for this expanded
      classification. The extended NrfA phylogeny revealed novel diagnostic features of
      DNRA populations and will be useful to assess nitrate/nitrite fate in natural and
      engineered ecosystems. 

PMID- 24463966
TI  - Phylogenetic differences in attached and free-living bacterial communities in a
      temperate coastal lagoon during summer, revealed via high-throughput 16S rRNA
      gene sequencing.
AB  - Most of what is known about coastal free-living and attached bacterial diversity
      is based on open coasts, with high particulate and nutrient riverine supply,
      terrestrial runoffs, and anthropogenic activities. The Magdalen Islands in the
      Gulf of St. Lawrence (Canada) are dominated by shallow lagoons with small,
      relatively pristine catchments and no freshwater input apart from rain. Such
      conditions provided an opportunity to investigate coastal free-living and
      attached marine bacterial diversity in the absence of confounding effects of
      steep freshwater gradients. We found significant differences between the two
      communities and marked temporal patterns in both. Taxonomic richness and
      diversity were greater in the attached than in the free-living community,
      increasing over summer, especially within the least abundant bacterial phyla. The
      highest number of reads fell within the SAR 11 clade (Pelagibacter,
      Alphaproteobacteria), which dominated free-living communities. The attached
      communities had deeper phylum-level diversity than the free-living fraction.
      Distance-based redundancy analysis indicated that the particulate organic matter
      (POM) concentration was the main variable separating early and late summer
      samples with salinity and temperature changes also significantly correlated to
      bacterial community structure. Our approach using high-throughput sequencing
      detected differences in free-living versus attached bacteria in the absence of
      riverine input, in keeping with the concept that marine attached communities are
      distinct from cooccurring free-living taxa. This diversity likely reflects the
      diverse microhabitats of available particles, implying that the total bacterial
      diversity in coastal systems is linked to particle supply and variability, with
      implications for understanding microbial biodiversity in marine systems. 

PMID- 24463967
TI  - New in situ capture quantitative (real-time) reverse transcription-PCR method as
      an alternative approach for determining inactivation of Tulane virus.
AB  - Human noroviruses (HuNoVs) are the major cause of epidemic nonbacterial
      gastroenteritis. Although quantitative (real-time) reverse transcription-PCR (qRT
      PCR) is widely used for detecting HuNoVs, it only detects the presence of viral
      RNA and does not indicate viral infectivity. Human blood group antigens (HBGAs)
      have been identified as receptors/co-receptors for both HuNoVs and Tulane virus
      (TV) and are crucial for viral infection. We propose that viral infectivity can
      be evaluated with a molecular assay based on receptor-captured viruses. In this
      study, we employed TV as an HuNoV surrogate to validate the HBGA-based capture
      qRT-PCR method against the 50% tissue culture infectious dose (TCID50) method. We
      employed type B HBGA on an immuno-well module to concentrate TV, followed by
      amplification of the captured viral genome by in situ qRT-PCR. We first
      demonstrated that this in situ capture qRT-PCR (ISC-qRT-PCR) method could
      effectively concentrate and detect TV. We then treated TV under either partial or
      full inactivation conditions and measured the remaining infectivity by ISC-qRT
      PCR and a tissue culture-based amplification method (TCID50). We found that the
      ISC-qRT-PCR method could be used to evaluate virus inactivation deriving from
      damage to the capsid and study interactions between the capsid and viral
      receptor. Heat, chlorine, and ethanol treatment primarily affect the capsid
      structure, which in turns affects the ability of the capsid to bind to viral
      receptors. Inactivation of the virus by these methods could be reflected by the
      ISC-qRT-PCR method and confirmed by TCID50 assay. However, the loss of the
      infectivity caused by damage to the viral genome (such as that from UV
      irradiation) could not be effectively reflected by this method. Despite this
      limitation, the ISC-qRT-PCR provides an alternative approach to determine
      inactivation of Tulane virus. A particular advantage of the ISC-qRT-PCR method is
      that it is also a faster and easier method to effectively recover and detect the
      viruses, as there is no need to extract viral RNA or to transfer the captured
      virus from magnetic beads to PCR tubes for further amplification. Therefore, ISC
      qRT-PCR can be easily adapted for use in automated systems for multiple samples. 

PMID- 24463968
TI  - Two new xylanases with different substrate specificities from the human gut
      bacterium Bacteroides intestinalis DSM 17393.
AB  - Xylan is an abundant plant cell wall polysaccharide and is a dominant component
      of dietary fiber. Bacteria in the distal human gastrointestinal tract produce
      xylanase enzymes to initiate the degradation of this complex heteropolymer. These
      xylanases typically derive from glycoside hydrolase (GH) families 10 and 11;
      however, analysis of the genome sequence of the xylan-degrading human gut
      bacterium Bacteroides intestinalis DSM 17393 revealed the presence of two
      putative GH8 xylanases. In the current study, we demonstrate that the two genes
      encode enzymes that differ in activity. The xyn8A gene encodes an endoxylanase
      (Xyn8A), and rex8A encodes a reducing-end xylose-releasing exo-oligoxylanase
      (Rex8A). Xyn8A hydrolyzed both xylopentaose (X5) and xylohexaose (X6) to a
      mixture of xylobiose (X2) and xylotriose (X3), while Rex8A hydrolyzed X3 through
      X6 to a mixture of xylose (X1) and X2. Moreover, rex8A is located downstream of a
      GH3 gene (xyl3A) that was demonstrated to exhibit beta-xylosidase activity and
      would be able to further hydrolyze X2 to X1. Mutational analyses of putative
      active site residues of both Xyn8A and Rex8A confirm their importance in
      catalysis by these enzymes. Recent genome sequences of gut bacteria reveal an
      increase in GH8 Rex enzymes, especially among the Bacteroidetes, indicating that
      these genes contribute to xylan utilization in the human gut. 

PMID- 24463969
TI  - Sustainable growth of Dehalococcoides mccartyi 195 by corrinoid salvaging and
      remodeling in defined lactate-fermenting consortia.
AB  - Corrinoids are essential cofactors of reductive dehalogenases in Dehalococcoides
      mccartyi, an important bacterium in bioremediation, yet sequenced D. mccartyi
      strains do not possess the complete pathway for de novo corrinoid biosynthesis.
      Pelosinus sp. and Desulfovibrio sp. have been detected in dechlorinating
      communities enriched from contaminated groundwater without exogenous cobalamin
      corrinoid. To investigate the corrinoid-related interactions among key members of
      these communities, we constructed consortia by growing D. mccartyi strain 195
      (Dhc195) in cobalamin-free, trichloroethene (TCE)- and lactate-amended medium in
      cocultures with Desulfovibrio vulgaris Hildenborough (DvH) or Pelosinus
      fermentans R7 (PfR7) and with both in tricultures. Only the triculture exhibited
      sustainable dechlorination and cell growth when a physiological level of 5,6
      dimethylbenzimidazole (DMB), the lower ligand of cobalamin, was provided. In the
      triculture, DvH provided hydrogen while PfR7 provided corrinoids to Dhc195, and
      the initiation of dechlorination and Dhc195 cell growth was highly dependent on
      the growth of PfR7. Corrinoid analysis indicated that Dhc195 imported and
      remodeled the phenolic corrinoids produced by PfR7 into cobalamin in the presence
      of DMB. Transcriptomic analyses of Dhc195 showed the induction of the CbiZ
      dependent corrinoid-remodeling pathway and BtuFCD corrinoid ABC transporter genes
      during corrinoid salvaging and remodeling. In contrast, another operon annotated
      to encode a putative iron/cobalamin ABC transporter (DET1174-DET1176) was induced
      when cobalamin was exogenously provided. Interestingly, a global upregulation of
      phage-related genes was observed when PfR7 was present. These findings provide
      insights into both the gene regulation of corrinoid salvaging and remodeling in
      Dhc195 when it is grown without exogenous cobalamin and microbe-to-microbe
      interactions in dechlorinating microbial communities. 

PMID- 24463970
TI  - Assessment of Giardia and Cryptosporidium spp. as a microbial source tracking
      tool for surface water: application in a mixed-use watershed.
AB  - Knowledge of host specificity, combined with genomic sequencing of Giardia and
      Cryptosporidium spp., has demonstrated a microbial source tracking (MST) utility
      for these common waterborne microbes. To explore the source attribution potential
      of these pathogens, water samples were collected in a mixed rural-urban watershed
      in the Township of Langley, in southwestern British Columbia (BC), Canada, over a
      2-year period. Cryptosporidium was detected in 63% of surface water samples at
      concentrations ranging from no positive detection (NPD) to 20,600 oocysts per 100
      liters. Giardia was detected in 86% of surface water samples at concentrations
      ranging from NPD to 3,800 cysts per 100 liters of water. Sequencing at the 18S
      rRNA locus revealed that 50% of Cryptosporidium samples and 98% of Giardia
      samples contained species/genotypes (Cryptosporidium) or assemblages (Giardia)
      that are capable of infecting humans, based on current knowledge of host
      specificity and taxonomy. Cryptosporidium genotyping data were more promising for
      source tracking potential, due to the greater number of host-adapted (i.e.,
      narrow-host-range) species/genotypes compared to Giardia, since 98% of Giardia
      isolates were zoonotic and the potential host could not be predicted. This report
      highlights the benefits of parasite genomic sequencing to complement Method 1623
      (U.S. Environmental Protection Agency) and shows that Cryptosporidium subtyping
      for MST purposes is superior to the use of Giardia subtyping, based on better
      detection limits for Cryptosporidium-positive samples than for Giardia-positive
      samples and on greater host specificity among Cryptosporidium species. These
      additional tools could be used for risk assessment in public health and watershed
      management decisions.

PMID- 24463971
TI  - Vibrio coralliilyticus strain OCN008 is an etiological agent of acute Montipora
      white syndrome.
AB  - Identification of a pathogen is a critical first step in the epidemiology and
      subsequent management of a disease. A limited number of pathogens have been
      identified for diseases contributing to the global decline of coral populations.
      Here we describe Vibrio coralliilyticus strain OCN008, which induces acute
      Montipora white syndrome (aMWS), a tissue loss disease responsible for
      substantial mortality of the coral Montipora capitata in Kane'ohe Bay, Hawai'i.
      OCN008 was grown in pure culture, recreated signs of disease in experimentally
      infected corals, and could be recovered after infection. In addition, strains
      similar to OCN008 were isolated from diseased coral from the field but not from
      healthy M. capitata. OCN008 repeatedly induced the loss of healthy M. capitata
      tissue from fragments under laboratory conditions with a minimum infectious dose
      of between 10(7) and 10(8) CFU/ml of water. In contrast, Porites compressa was
      not infected by OCN008, indicating the host specificity of the pathogen. A
      decrease in water temperature from 27 to 23 degrees C affected the time to
      disease onset, but the risk of infection was not significantly reduced.
      Temperature-dependent bleaching, which has been observed with the V.
      coralliilyticus type strain BAA-450, was not observed during infection with
      OCN008. A comparison of the OCN008 genome to the genomes of pathogenic V.
      coralliilyticus strains BAA-450 and P1 revealed similar virulence-associated
      genes and quorum-sensing systems. Despite this genetic similarity, infections of
      M. capitata by OCN008 do not follow the paradigm for V. coralliilyticus
      infections established by the type strain. 

PMID- 24463972
TI  - Whole-genome single-nucleotide-polymorphism analysis for discrimination of
      Clostridium botulinum group I strains.
AB  - Clostridium botulinum is a genetically diverse Gram-positive bacterium producing
      extremely potent neurotoxins (botulinum neurotoxins A through G [BoNT/A-G]). The
      complete genome sequences of three strains harboring only the BoNT/A1 nucleotide
      sequence are publicly available. Although these strains contain a toxin cluster
      (HA(+) OrfX(-)) associated with hemagglutinin genes, little is known about the
      genomes of subtype A1 strains (termed HA(-) OrfX(+)) that lack hemagglutinin
      genes in the toxin gene cluster. We sequenced the genomes of three BoNT/A1
      producing C. botulinum strains: two strains with the HA(+) OrfX(-) cluster (69A
      and 32A) and one strain with the HA(-) OrfX(+) cluster (CDC297). Whole-genome
      phylogenic single-nucleotide-polymorphism (SNP) analysis of these strains along
      with other publicly available C. botulinum group I strains revealed five distinct
      lineages. Strains 69A and 32A clustered with the C. botulinum type A1 Hall group,
      and strain CDC297 clustered with the C. botulinum type Ba4 strain 657. This study
      reports the use of whole-genome SNP sequence analysis for discrimination of C.
      botulinum group I strains and demonstrates the utility of this analysis in
      quickly differentiating C. botulinum strains harboring identical toxin gene
      subtypes. This analysis further supports previous work showing that strains
      CDC297 and 657 likely evolved from a common ancestor and independently acquired
      separate BoNT/A1 toxin gene clusters at distinct genomic locations. 

PMID- 24463973
TI  - Persistence of infectious Shiga toxin-encoding bacteriophages after disinfection
      treatments.
AB  - In Shiga toxin-producing Escherichia coli (STEC), induction of Shiga toxin
      encoding bacteriophages (Stx phages) causes the release of free phages that can
      later be found in the environment. The ability of Stx phages to survive different
      inactivation conditions determines their prevalence in the environment, the risk
      of stx transduction, and the generation of new STEC strains. We evaluated the
      infectivity and genomes of two Stx phages (Phi534 and Phi557) under different
      conditions. Infectious Stx phages were stable at 4, 22, and 37 degrees C and at
      pH 7 and 9 after 1 month of storage but were completely inactivated at pH 3.
      Infective Stx phages decreased moderately when treated with UV (2.2-log10
      reduction for an estimated UV dose of 178.2 mJ/cm(2)) or after treatment at 60
      and 68 degrees C for 60 min (2.2- and 2.5-log10 reductions, respectively) and
      were highly inactivated (3 log10) by 10 ppm of chlorine in 1 min. Assays in a
      mesocosm showed lower inactivation of all microorganisms in winter than in
      summer. The number of Stx phage genomes did not decrease significantly in most
      cases, and STEC inactivation was higher than phage inactivation under all
      conditions. Moreover, Stx phages retained the ability to lysogenize E. coli after
      some of the treatments. 

PMID- 24463974
TI  - Environmental survival of Mycobacterium avium subsp. paratuberculosis in
      different climatic zones of eastern Australia.
AB  - The duration of survival of both the S and C strains of Mycobacterium avium
      subsp. paratuberculosis in feces was quantified in contrasting climatic zones of
      New South Wales, Australia, and detailed environmental temperature data were
      collected. Known concentrations of S and C strains in feces placed on soil in
      polystyrene boxes were exposed to the environment with or without the provision
      of shade (70%) at Bathurst, Armidale, Condobolin, and Broken Hill, and subsamples
      taken every 2 weeks were cultured for the presence of M. avium subsp.
      paratuberculosis. The duration of survival ranged from a minimum of 1 week to a
      maximum of 16 weeks, and the provision of 70% shade was the most important factor
      in extending the survival time. The hazard of death for exposed compared to
      shaded samples was 20 and 9 times higher for the S and C strains, respectively.
      Site did not affect the survival of the C strain, but for the S strain, the
      hazard of death was 2.3 times higher at the two arid zone sites (Broken Hill and
      Condobolin) than at the two temperate zone sites (Bathurst and Armidale).
      Temperature measurements revealed maximum temperatures exceeding 60 degrees C and
      large daily temperature ranges at the soil surface, particularly in exposed
      boxes.

PMID- 24463977
TI  - Neutrophil CD64 as a diagnostic marker of sepsis in neonates.
AB  - BACKGROUND: Sepsis in neonates hospitalized in the neonatal intensive care unit
      is a global problem and is a significant contributor to morbidity and mortality.
      Neutrophil surface CD64, the high-affinity Fc receptor, is quantitatively up
      regulated during infection and sepsis. OBJECTIVE: Our goal in this prospective
      study was to measure the neutrophil CD64 in blood as an adjunct to our previously
      validated hematologic scoring system for detecting neonatal sepsis. METHODS: A
      prospective study enrolled newborns with documented sepsis (n = 25), clinical
      sepsis (n = 25), and control newborns (n = 25). C-reactive protein, neutrophil
      CD64, complete blood counts, and blood cultures were taken. Neutrophil CD64 was
      analyzed by flow cytometry. RESULTS: CD64 was significantly elevated in the
      groups with documented and clinical sepsis (P < 0.001). CD64 had a sensitivity of
      96%, a specificity of 100%, a positive predictive value of 96.2%, and a negative
      predictive value of 100% with a cutoff value of 45.8% and 46.0% in the confirmed
      and the clinical sepsis groups, respectively. CONCLUSIONS: CD64 expression on
      neutrophils increases significantly in neonates with sepsis and can be considered
      a useful diagnostic marker for early diagnosis of neonatal infection as a single
      determination compared with other inflammatory markers.

PMID- 24463976
TI  - Thermostability improvement of a streptomyces xylanase by introducing proline and
      glutamic acid residues.
AB  - Protein engineering is commonly used to improve the robustness of enzymes for
      activity and stability at high temperatures. In this study, we identified four
      residues expected to affect the thermostability of Streptomyces sp. strain S9
      xylanase XynAS9 through multiple-sequence analysis (MSA) and molecular dynamic
      simulations (MDS). Site-directed mutagenesis was employed to construct five
      mutants by replacing these residues with proline or glutamic acid (V81P, G82E,
      V81P/G82E, D185P/S186E, and V81P/G82E/D185P/S186E), and the mutant and wild-type
      enzymes were expressed in Pichia pastoris. Compared to the wild-type XynAS9, all
      five mutant enzymes showed improved thermal properties. The activity and
      stability assays, including circular dichroism and differential scanning
      calorimetry, showed that the mutations at positions 81 and 82 increased the
      thermal performance more than the mutations at positions 185 and 186. The mutants
      with combined substitutions (V81P/G82E and V81P/G82E/D185P/S186E) showed the most
      pronounced shifts in temperature optima, about 17 degrees C upward, and their
      half-lives for thermal inactivation at 70 degrees C and melting temperatures were
      increased by >9 times and approximately 7.0 degrees C, respectively. The mutation
      combination of V81P and G82E in adjacent positions more than doubled the effect
      of single mutations. Both mutation regions were at the end of long secondary
      structure elements and probably rigidified the local structure. MDS indicated
      that a long loop region after positions 81 and 82 located at the end of the inner
      beta-barrel was prone to unfold. The rigidified main chain and filling of a
      groove by the mutations on the bottom of the active site canyon may stabilize the
      mutants and thus improve their thermostability. 

PMID- 24463978
TI  - Ninety-day survival rate of patients with sepsis relates to programmed cell death
      1 genetic polymorphism rs11568821.
AB  - BACKGROUND: Sepsis is a life-threatening condition. Programmed cell death 1
      protein (PD-1), a negative costimulatory molecule, is suggested to be involved in
      pathogenesis as mortality is associated with high expression and as neutralizing
      antibodies improve survival in a mouse model. The PD-1 gene harbors an intronic
      single-nucleotide polymorphism, rs11568821, which is located in a transcription
      factor-binding site and supposed to affect PD-1 transcription. OBJECTIVE: This
      study aimed at investigating whether mortality (90-day) among patients with
      sepsis associates with PD-1 rs11568821 genotypes. METHODS: Adult white patients
      with sepsis from the surgical intensive care units of a university medical center
      were followed up for 90 days, and mortality was recorded as primary outcome
      variable. Blood samples were taken for PD-1 rs11568821 genotyping. Sequential
      Organ Failure Assessment scores increased at enrollment and during the
      observation period to monitor morbidity. RESULTS: Two hundred nineteen critically
      ill patients with sepsis were enrolled in this investigation. Ninety-day
      mortality was significantly higher among G homozygotes than among A allele
      carriers (P = 0.0032). During intensive care unit stay, G homozygotes experienced
      higher Sequential Organ Failure Assessment scores (P < 0.001) and a higher demand
      of vasopressor therapy (P = 0.0107). CONCLUSIONS: Data provide first associative
      evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.

PMID- 24463975
TI  - Distribution of sequence-based types of legionella pneumophila serogroup 1
      strains isolated from cooling towers, hot springs, and potable water systems in
      China.
AB  - Legionella pneumophila serogroup 1 causes Legionnaires' disease. Water systems
      contaminated with Legionella are the implicated sources of Legionnaires' disease.
      This study analyzed L. pneumophila serogroup 1 strains in China using sequence
      based typing. Strains were isolated from cooling towers (n = 96), hot springs (n
      = 42), and potable water systems (n = 26). Isolates from cooling towers, hot
      springs, and potable water systems were divided into 25 sequence types (STs;
      index of discrimination [IOD], 0.711), 19 STs (IOD, 0.934), and 3 STs (IOD,
      0.151), respectively. The genetic variation among the potable water isolates was
      lower than that among cooling tower and hot spring isolates. ST1 was the
      predominant type, accounting for 49.4% of analyzed strains (n = 81), followed by
      ST154. With the exception of two strains, all potable water isolates (92.3%)
      belonged to ST1. In contrast, 53.1% (51/96) and only 14.3% (6/42) of cooling
      tower and hot spring, respectively, isolates belonged to ST1. There were
      differences in the distributions of clone groups among the water sources. The
      comparisons among L. pneumophila strains isolated in China, Japan, and South
      Korea revealed that similar clones (ST1 complex and ST154 complex) exist in these
      countries. In conclusion, in China, STs had several unique allelic profiles, and
      ST1 was the most prevalent sequence type of environmental L. pneumophila
      serogroup 1 isolates, similar to its prevalence in Japan and South Korea. 

PMID- 24463979
TI  - Interleukin 8 inhibition enhanced cholesterol efflux in acetylated low-density
      lipoprotein-stimulated THP-1 macrophages.
AB  - Cholesterol efflux plays a major role in antiatherogenesis, and modification of
      this process may provide a new therapeutic approach to cardiovascular disease.
      Interleukin 8 (IL-8) is implicated in various aspects of atherosclerosis.
      However, the effect of IL-8 on cholesterol efflux is still unclear. Here, we used
      human IL-8-neutralizing antibody to inhibit IL-8 and analyze the function of IL-8
      in cholesterol efflux from acetylated low-density lipoprotein-loaded THP-1
      macrophages. Acetylated low-density lipoprotein loading resulted in an
      approximately 2.5-fold increase in both the mRNA and protein levels of IL-8 in
      THP-1 macrophages, when compared with nonloaded THP-1 macrophages (P < 0.01).
      Five and 10 ug/mL of human IL-8-neutralizing antibody enhanced cholesterol efflux
      from THP-1-derived macrophages by 1.2- and 1.4-fold, respectively. Moreover, anti
      IL-8-treated cells showed increased expression of peroxisome proliferator
      activated gamma, liver X receptor alpha, and ATP-binding cassette transporter A1
      at both the mRNA and protein levels. Ten micromoles of SB203580, an inhibitor of
      p38, almost completely suppressed the production of IL-8 from acetylated low
      density lipoprotein-loaded THP-1 macrophages and accelerated cholesterol efflux.
      Taken together, our results indicate that IL-8 exerts negative regulatory effects
      on cholesterol efflux from THP-1 cells and may thus represent a potential target
      for prevention and treatment of atherosclerosis. 

PMID- 24463980
TI  - One-staged or two-staged surgery for perforated choledochal cyst with bile
      peritonitis in children? A single center experience with 27 cases.
AB  - PURPOSE: To report the authors' experience in the management of perforated
      choledochal cyst with bile peritonitis (PCC) in children. METHODS: Medical
      records of all children undergoing surgery for PCC at our hospital from May, 2005
      to January, 2013 were reviewed. RESULTS: Twenty seven patients were identified,
      with a median age of 2 years. The clinical manifestations were abdominal pain
      (96.3 %), abdominal distention (92.6 %), vomiting (88.9 %), jaundice (74.1 %),
      fever (70.4 %), acholic stool (51.8 %), abdominal tenderness (92.6 %), peritoneal
      signs (74.1 %), and palpable mass (18.5 %). Duration of the acute symptoms ranged
      from 1 to 30 days (median 3 days). Median size of the choledochal cysts was 3 cm
      (range 1.5-18 cm). Before January 2008, four cases were treated by two-staged
      surgery and only one case by one-staged surgery. Since then, all remaining 22
      cases were treated by the one-staged surgery. There was no anastomotic leakage
      and all patients were discharged in good health. The mean postoperative stay was
      7.6 +/- 2.5 days for the one-staged group. No complication was noted at a median
      follow-up of 24 months. CONCLUSIONS: One-staged definitive repair is feasible,
      safe and should be the treatment of choice for most cases of childhood PCC in
      experienced centers.

PMID- 24463981
TI  - Redox-responsive thermal sensitivity based on a selenium-containing small
      molecule.
AB  - Thermoresponsive spherical assemblies formed by a selenium-containing small
      molecule exhibit lower critical solution temperature (LCST) behavior in aqueous
      solution, which can be reversibly switched by mild redox treatment. 

PMID- 24463982
TI  - Mandibular advancement device and CPAP upon cardiovascular parameters in OSA.
AB  - PURPOSE: This study aims to compare the effects of a mandibular advancement
      device (MAD) with continuous positive airway pressure (CPAP) treatment for
      obstructive sleep apnea (OSA) on blood pressure (BP), oxidative stress, and heart
      rate variability (HRV) in a randomized, crossed-over, single-blind, and
      controlled trial. METHODS: Twenty-nine moderate-to-severe adult OSA patients
      underwent MAD, CPAP, and placebo oral appliance treatment. Polysomnography,
      Epworth sleepiness scale, 24-h ambulatory BP monitoring, oxidative stress
      parameters (malondialdehyde, catalase, superoxide dismutase, vitamins C, E, B6,
      B12, folate, homocysteine, uric acid), and HRV were assessed at baseline and
      after 1 month of each treatment. Diaries were used to evaluate compliance for
      devices and a pressure-time meter for CPAP. RESULTS: Both active treatments
      resulted in decreases in apnea and hypopnea index and Epworth sleepiness scale;
      CPAP showed a greater effect. Frequency of diastolic BP dipping was higher in the
      MAD group compared with the CPAP group. A significant drop from baseline levels
      for catalase activity was observed after MAD. For HRV, there was a significant
      decrease in total power at night with CPAP and MAD compared with POA, and a
      decrease in index of sleep autonomic variation with MAD compared with baseline
      levels. Compliance rates were higher with MAD rather than CPAP. CONCLUSIONS: Even
      though CPAP proved to be more effective at attenuating OSA, better compliance
      with MAD favored the reduction of one of the enzymes which participates in
      oxidative stress and better autonomic modulation during sleep.

PMID- 24463983
TI  - Effect of continuous positive airway pressure on homocysteine levels in patients
      with obstructive sleep apnea: a meta-analysis.
AB  - PURPOSE: Continuous positive airway pressure (CPAP) is an effective treatment for
      obstructive sleep apnea hypopnea syndrome (OSAHS), but previous studies assessing
      the effect of CPAP on homocysteine (HCY) in patients with OSAHS yielded
      conflicting results. In this study, we conducted a meta-analysis to determine
      whether CPAP therapy could reduce plasma HCY levels. METHODS: Searches of PUBMED,
      SCI, and Elsevier databases were completed. Studies of adult patients with OSAHS
      who reported HCY levels pre- and post-CPAP treatment were collected by two
      independent reviewers. RevMan (version 5.2) and STATA (version 12.0) were used to
      perform data synthesis. RESULTS: A total of 6 studies involving 206 participants
      were included. Meta-analysis showed that the total weighted mean difference (WMD)
      for HCY levels was -0.62 units (95% confidence interval (CI) -1.21 to -0.04,
      P<0.05) post- and pre-CPAP therapy. Subgroup analysis showed that HCY was
      decreased nonsignificantly within 3 months after the therapy (WMD, -0.07, 95% CI 
      0.88 to 0.74, P>0.05), but it was significantly reduced after 3 months therapy
      (WMD, -1.22, 95% CI -2.07 to -0.38, P<0.05). CONCLUSIONS: This meta-analysis
      suggests that HCY levels were significantly reduced by CPAP therapy in patients
      with OSAHS and the HCY levels may be clinically recognized as a valuable
      indicator for OSAHS treatment, but the clinical significance of this finding as
      it relates to cardiovascular risk reduction in OSAHS patients warrants further
      study.

PMID- 24463984
TI  - Weapon carrying, physical fighting and gang membership among youth in Washington
      state military families.
AB  - To examine associations between parental military service and school-based weapon
      carrying, school-based physical fighting and gang membership among youth. We used
      cross-sectional data from the 2008 Washington State Healthy Youth Survey
      collected in 8th, 10th, and 12th grades of public schools (n = 9,987). Parental
      military service was categorized as none (reference group), without combat zone
      deployment, or deployed to a combat zone. Multivariable logistic regression was
      used to test associations between parental military service and three outcomes:
      school-based weapon carrying, school-based physical fighting and gang membership.
      Standard errors were adjusted for the complex survey design. In 8th grade,
      parental deployment was associated with higher odds of reporting gang membership
      (OR = 1.8) among girls, and higher odds of physical fighting (OR = 1.6), and gang
      membership (OR = 1.9) among boys. In 10th/12th grade, parental deployment was
      associated with higher odds of reporting physical fighting (OR = 2.0) and gang
      membership (OR = 2.2) among girls, and physical fighting (OR = 2.0), carrying a
      weapon (OR = 2.3) among boys. Parental military deployment is associated with
      increased odds of reporting engagement in school-based physical fighting, school
      based weapon carrying, and gang membership, particularly among older youth.
      Military, school, and public health professionals have a unique, collaborative
      opportunity to develop school- and community-based interventions to prevent
      violence-related behaviors among youth and, ultimately, improve the health and
      safety of youth in military families. Ideally, such programs would target
      families and youth before they enter eighth grade.

PMID- 24463985
TI  - Multicompartment management of patients with severe traumatic brain injury.
AB  - PURPOSE OF REVIEW: Intracranial pressure (ICP) control is a mainstay of traumatic
      brain injury (TBI) management. However, development of intracranial hypertension
      (ICH) may be affected by factors outside of the cranial vault in addition to the
      local effects of the TBI. This review will examine the pathophysiology of
      multiple compartment syndrome (MCS) and current treatment considerations for
      patients with TBI given the effects of MCS. RECENT FINDINGS: Elevated intra
      abdominal pressure (IAP) is associated with ICP elevation, and decompressive
      laparotomy in patients with concurrent elevations in IAP and ICP can reduce ICP.
      Elevated intrathoracic pressure may be similarly associated with ICP elevation,
      although the ideal ventilator management strategy for TBI patients when
      considering MCS is unclear. SUMMARY: In MCS, intracranial, intrathoracic and
      intra-abdominal compartment pressures are interrelated. TBI patient care should
      include ICP control as well as minimization of intrathoracic and intra-abdominal
      pressure as clinically possible.

PMID- 24463986
TI  - Particle tracking by full-field complex wavefront subtraction in digital
      holography microscopy.
AB  - The 3D tracking of micro-objects, based on digital holography, is proposed
      through the analysis of the complex wavefront of the light scattered by the micro
      samples. Exploiting the advantages of the off-axis full-field holographic
      interferometry, the tracking of multiple objects is achieved by a direct
      wavefront analysis at the focal plane overcoming the limitation of the
      conventional back focal plane interferometry in which only one object at a time
      can be tracked. Furthermore, the method proposed and demonstrated here is a step
      forward with respect to other holographic tracking tools. The approach is tested
      in two experiments, the first investigates the Brownian motion of particles
      trapped by holographic optical tweezers, while the second relates to the cell
      motility in a 3D collagen matrix, thus showing its usefulness for lab-on-chip
      systems in typical bioassay testing. 

PMID- 24463988
TI  - Legal and ethical responsibilities following brain death: the McMath and Munoz
      cases.

PMID- 24463987
TI  - Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix
      in defined and xeno-free environment.
AB  - Lack of robust methods for establishment and expansion of pluripotent human
      embryonic stem (hES) cells still hampers development of cell therapy. Laminins
      (LN) are a family of highly cell-type specific basement membrane proteins
      important for cell adhesion, differentiation, migration and phenotype stability.
      Here we produce and isolate a human recombinant LN-521 isoform and develop a cell
      culture matrix containing LN-521 and E-cadherin, which both localize to stem cell
      niches in vivo. This matrix allows clonal derivation, clonal survival and long
      term self-renewal of hES cells under completely chemically defined and xeno-free
      conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable
      clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line
      derivation from blastocyst inner cell mass and single blastomere cells without a
      need to destroy the embryo. This method can facilitate the generation of hES cell
      lines for development of different cell types for regenerative medicine purposes.

PMID- 24463989
TI  - Estimating farm-level private expenditure on veterinary medical inputs in
      England.
AB  - The current re-evaluation of responsibility and cost sharing between the public
      and private sectors with reference to animal health and welfare (AHW) would be
      improved by a greater understanding of the contributions made at farm level. This
      knowledge would facilitate the design of a cost-sharing system which best
      balances technical, economic and political objectives. This paper presents a
      framework by which the farm-level investment in AHW can be assessed. An
      evaluation of data available for the framework was made and, as a benchmark, an
      estimate of total expenditure on veterinary medical inputs for commercial
      agricultural holdings in England calculated. In 2010/2011 it is calculated that
      farmers on commercial holdings in England spent L230 million on veterinary
      medicines and fees, with an additional L160 million being spent for horses kept
      on non-commercial holdings. By contrast, for 2012/2013, Defra budgeted L277
      million on AHW. The results presented emphasise the critical importance of
      generating sufficient evidence to support the development of an efficient,
      equitable and sustainable AHW strategy. 

PMID- 24463990
TI  - First report of canine leprosy in Europe: molecular and clinical traits.

PMID- 24463991
TI  - Outcome of surgical treatment for umbilical swellings in bovine youngstock.
AB  - Umbilical swellings are commonly identified in calves and can be caused by hernia
      formation, infection of the remnants of umbilical vessels or a combination of
      both. Ninety-one cases with umbilical swellings were admitted to the Leahurst
      Farm Animal Practice (LFAP) between July 2004 and February 2012; 55 were simple
      hernias and 36 had associated infection. Eighty-seven cases underwent surgery of
      which 86 survived until discharge. Postoperative complications occurred in 65/86
      animals (73 per cent). In 51 cases (81 per cent) this was classified as minor
      requiring no additional treatment. Placement of a prosthetic mesh was associated
      with a higher OR for developing severe postoperative complication when compared
      with those not receiving a mesh (OR=19.3; 95% CI 4.5 to 83.5). Long-term survival
      results were available for 49 animals, 22 of which were remaining in the herd
      with a median age of 1346 days (3.7 years). Of the 27 animals which had exited
      the herd, 16 were adult dairy cows, 7 were dairy heifers, 2 were beef animals and
      2 exited at an unknown stage. Umbilical surgery in calves carries a good
      prognosis, although placement of a mesh increases the risk of complications
      occurring in the postoperative period. 

PMID- 24463992
TI  - FPL-vaccinated cats are protected from CPV2c and CPV2b challenge.

PMID- 24463993
TI  - Mesna and furosemide for prevention of cyclophosphamide-induced sterile
      haemorrhagic cystitis in dogs--a retrospective study.
AB  - Sterile haemorrhagic cystitis (SHC) is a possible side effect of cyclophosphamide
      which can severely impact quality of life. Mesna and diuresis are effective in
      human medicine to prevent SHC. The aim of the present study was to compare the
      efficacy of mesna versus diuresis with furosemide in preventing SHC in dogs
      treated with cyclophosphamide within a multidrug chemotherapy induction protocol
      for malignant lymphoma. Medical records of dogs treated at the Clinic of Small
      Animal Medicine, Munich, between 1997 and 2009 were analysed retrospectively. Of
      the 131 dogs included, 33 received no prophylaxis (group 1), 43 received mesna
      (group 2), and 55 received furosemide (group 3). Age, gender, breed, bodyweight,
      body surface area, dose and application method of cyclophosphamide, and the
      method of SHC prophylaxis were compared between dogs with and without SHC. Six
      dogs (4.6 per cent) developed SHC. The incidence of SHC in groups 1, 2 and 3 was
      4/33 (12.1 per cent), 1/43 (2.3 per cent), and 1/55 (1.8 per cent), respectively.
      Dogs receiving either mesna or furosemide were significantly less likely to
      develop SHC (P=0.03). Otherwise no significant differences were found. In
      conclusion, this study demonstrates the efficacy and the medical indication of
      mesna and furosemide for prevention of cyclophosphamide-induced SHC.

PMID- 24463994
TI  - Nerve conduction velocities in hyperlipidemic patients.
AB  - OBJECTIVES: Metabolic disease affect all systems in the body, including the
      peripheral nervous system, but there is a controversy as whether to consider
      hyperlipidemia is a cause of peripheral neuropathy. The aim of the present study
      was to evaluate whether hyperlipidemic subjects with no clinical symptom or sign
      of peripheral neuropathy showed nerve conduction abnormalities or subclinical
      peripheral neuropathy according to the universally accepted electrophysiological
      criteria. METHODS: The study group consisted from 29 female and 16 male patients
      (mean age: 47+/-7) while the control group consisted from 22 female and 10 male
      healthy volunteer subjects with a mean age of (43+/-9). All participants
      underwent an electrographic study in the classical manner described in the
      literature. Median and ulnar nerves in one upper, peroneal posterior tibial and
      sural nerves were studied in both lower extremities. RESULTS: Median nerve 2nd
      digit-wrist segment sensory nerve conduction velocity were slow and sensory nerve
      action potential amplitude (SNAP) were low relative to controls. Sural nerve
      sensory nerve conduction velocity in the lower extremities were low relative to
      controls. DISCUSSION: In this study the hyperlipemic group consisted from
      subjects with a relatively young age and with not very high serum lipid levels.
      Finding abnormal nerve conduction in distal sensory nerves in both upper and
      lower extremities in these hyperlipidemic patients made us think that; aging or
      uncontrolled hyperlipidemia may make these subjects susceptible to generalized
      peripheral neuropathy in the future. CONCLUSION: Hyperlipidemia may affect nerve
      conduction in peripheral nerves and precede peripheral neuropathy.

PMID- 24463995
TI  - 48-hours administration of nifedipine in spontaneous preterm labor - Doppler
      blood flow assessment of placental and fetal circulation.
AB  - OBJECTIVES: The aims were to assess the placental and fetal circulation during
      nifedipine tocolysis within the first 48 hours of therapy. METHODS: Placental and
      fetal circulation was assessed in Doppler ultrasound examination prior to
      nifedipine administration and then after 24 and 48 hours. Maternal heart rate and
      PI in uterine arteries were evaluated as well as FHR, RI and PI of UA and MCA.
      E/A-wave ratio for A-V valves, MPI and SF were calculated for both ventricles
      independently. To determine changes over time in all study variable analysis of
      variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple
      comparison test was used. The effects of additional clinical covariates were
      checked. RESULTS: Uterine and umbilical blood flow patterns were not altered
      significantly during administration of nifedypine tocolysis. While MCA Doppler
      indicies such as RI and PI were unchanged, the evaluation of MCA PSV revealed a
      transient significant decrease after 24 hours. A resolution of this distraction
      was observed within the following 24 hours. No significant changes were observed
      in direct fetal cardiac function parameters calculated separately for both
      ventricles. CONCLUSIONS: The decrease of MCA PSV after 24 hours of treatment was
      isolated and transient hemodynamic distraction observed during treatment. Neither
      fetal cardiac parameters nor other Doppler indices were changed. Therefore oral
      administration of nifedipine seems not to alter uterine nor fetal arterial blood
      flow pattern seriously. As significant changes were observed by different
      authors, further studies should be performed to verify the optimal total dose of
      nifedipine and its influence on hemodynamic conditions.

PMID- 24463996
TI  - A case report of overlapping Bickerstaff brainstem encephalitis and Guillain
      Barre syndrome.
AB  - We report a case of a 23-year-old man diagnosed with overlapping Bickerstaff
      brainstem encephalitis (BBE) and Guillain-Barre syndrome (GBS). The patient
      initially presented with fever and headache and gradually developed ataxia,
      disturbance of consciousness, respiratory muscle paralysis, bilateral facial
      paralysis and quadriplegia accompanied by significant atrophy of limb, temporalis
      and masseter muscles. Brain MRI revealed abnormality in the left basal ganglia,
      thalamus, and rightside posterior limb of the internal capsule. Electromyogram
      indicated neurogenic damage (mainly axonal damage) in the upper and lower limbs
      and bilateral facial nerve damage. Cerebrospinal fluid (CSF) collected via lumbar
      puncture was colorless and transparent with a pressure of 330 mm H2O. The white
      blood cell count in CSF was 200*106/L, the protein concentration was 1.25 g/L,
      and Pandy's reaction was positive. Both the blood and CSF were negative for GQ1b
      antibody. The patient was clinically diagnosed with overlapping BBE and GBS.
      After treatment with ventilator assisted breathing, hormone therapy, neurotrophic
      and anti-infection therapies, and symptomatic and supportive care for more than
      three months, spontaneous breathing was restored. By the 5-month follow-up
      examination, the patient had completely recovered and returned to work. Like GBS
      and Fisher syndrome, BBE might be an anti-GQlb IgG antibody syndrome. Although
      the serum GQlb IgG antibody-positive rate for BBE is only 66%, a normal brainstem
      MRI or GQlb lgG antibody-negative finding cannot completely rule out BBE.
      Therefore, identifying critical illness polyneuropathy for patients with
      respiratory muscle paralysis and tracheal extubation difficulties at early stages
      is clinically important.

PMID- 24463997
TI  - A psychophysical theory of Shannon entropy.
AB  - Connections between information theory and decision under uncertainty have been
      attracting attention in econophysics, neuroeconomics and quantum decision theory.
      This paper proposes a psychophysical theory of Shannon entropy based on a
      mathematical equivalence of delay and uncertainty in decision-making, and
      psychophysics of the perception of waiting time in probabilistic choices.
      Furthermore, it is shown that the well-known Shannon entropy is a special case of
      the general psychophysical entropy. Future directions in the application of the
      present theory to studies in econophysics and neuroeconomics are discussed.

PMID- 24463998
TI  - Adult idiopathic isolated ACTH deficiency: a short series and literature review.
AB  - OBJECTIVES: Adult idiopathic isolated ACTH deficiency (AIIAD) is an
      underestimated disorder which is frequently misdiagnosed. We presented 3 new
      Chinese AIIAD cases, summarized their clinical characteristics and analyzed the
      available literature. METHODS: Three cases of AIIAD managed in Chinese PLA
      General Hospital during the period 1998-2003 were retrospectively identified. We
      have collected information on clinical presentation, laboratory findings and
      treatment response. The clinical characteristics were summarized and pertinent
      literatures were analyzed. RESULTS: Our 3 cases with AIIAD aged 52-68 years old
      were misdiagnosed for a long period of time. Clinical features of AIIAD were
      summarized by reviewing the limited literature: 1. Most patients were over 40
      years; 2. Clinical presentations were insidious; 3. Usually no pigmentation; 4.
      Hypogonadism and amenorrhea could present; 5. mild hypoglycemia, hyponatremia,
      normal-high potassium, mild anemia, lymphocytosis and eosinophilia could present;
      6. With low or absent cortisol, normal secretion of pituitary hormones other than
      ACTH; 7. High prevalence of thyroid disorder; 8. Usually present concomitantly
      with other autoimmune disease, which usually disappeared on steroid replacement;
      9. Absence of structural pituitary defects except for empty sella; 10. No
      evidence in any infiltration, trauma, surgery, infectious or radiotherapy, or
      glucocorticoid medication; 11. No growth abnormalities. CONCLUSION: AIIAD is an
      unspecified and underestimated condition with much misdiagnosis. We summarized
      the clinical features to improve the recognition. Indeed, every patient with
      unexplained hyponatremia and malaise, particularly in patients with autoimmune
      diseases, needs to be evaluated for the possibility of AIIAD.

PMID- 24463999
TI  - Advantages and disadvantages of over-the-counter availability of emergency
      contraception.
AB  - OBJECTIVES: To compare usage patterns, accessibility and knowledge about over-the
      counter (OTC) emergency contraception (EC) in comparison to prescription-only EC.
      DESIGN AND SETTING: Self-designed, paper-based validated questionnaires
      containing 26 questions were distributed among students and high school pupils in
      Poland (PL) - 1000 questionnaires and in Lithuania (LT) - 650. In Lithuania EC is
      available OTC, whereas in Poland EC is a prescription-only drug. Statistical
      analysis was performed using SAS software with p<0.05 considered significant.
      RESULTS: 74.01% of Poles and 70.89% of Lithuanians reported a history of sexual
      activity. About one third of the respondents in both countries used EC at least
      once in a lifetime (PL: 29.01%, LT: 32.2%; p>0.05). The main reason for EC usage
      in both countries was a broken condom (PL: 60.63%, LT: 57.66 %; p>0.05). In case
      of emergency more than half of the questioned women in both countries would use
      EC pill. The knowledge about EC was significantly lower in Poland (PL median - 8
      out of 16; LT - 10 out of 16 true/false statements; p<0.01). CONCLUSIONS: Over
      the-counter availability of EC does not cause repetitive or increased usage.
      Moreover, an easier access to EC improves patients' knowledge about the drug.

PMID- 24464000
TI  - Cardiovascular risk and the use of oral contraceptives.
AB  - The use of combined oral contraceptives (COCs) is associated with approximately 2
      fold and over 4-fold increased relative risks of arterial and venous
      thromboembolic events, respectively. The highest risk of venous thromboembolism
      occurs in the first year of use (OR: 4.17) and is reduced to 2.76 over baseline
      risk after 4 years of therapy. The risk of myocardial infarction does not
      correlate to the length of therapy and disappears after treatment termination.
      Most of women, using COCs, have low absolute cardiovascular risks and benefits
      outweigh the risk associated with this method of birth control. However, in some
      cases, COCs may be contraindicated due to excessively increased cardiovascular
      risks. Current users of COCs, older than 35 years, appear to show an estimated
      2.5-fold and 10-fold increased risk of venous thromboembolism in comparison to
      younger than 35 years COCs non-users and users, respectively. COCs users, who are
      current smokers, have 10-fold increased risk of myocardial infarction, whereas
      the risk of stroke increases nearly 3-fold. The presence of poorly controlled
      hypertension is associated with approximately 3-fold increased risks of
      myocardial infarction and ischemic stroke, while the risk of haemorrhagic stroke
      rises 15-fold. In women suffering from hypertension, discontinuation of COCs may
      improve blood pressure control. Women, who had their blood pressure measured
      before COCs use, have 2-2.5-fold decreased risk of myocardial infarction and
      ischaemic stroke. In women with multiple cardiovascular risk factors the use of
      progestogen-only contraceptives (POCs) should be considered. POC therapy is
      associated with substantially less risk of cardiovascular events than COCs.

PMID- 24464001
TI  - Cognitive functions, apolipoprotein E genotype and hormonal replacement therapy
      of postmenopausal women.
AB  - OBJECTIVE: The results of many studies revealed that estrogen plus progestogen
      therapy (EPT) may modify dementia development risk in relation to the
      apolipoprotein E gene (APOE) polymorphisms. However, the mechanism and
      subsequently clinical importance of such an effect are still unexplained. The
      objective of this study was to explore the influence of EPT on cognitive
      functioning of women in their postmenopausal life in relation to APOE
      polymorphism. METHODS: The group of 214 women was recruited (106 out of this
      group with EPT) to the study. The inclusion criteria were: minimum two years
      after the last menstruation, FSH concentration over 30 U/ml and no dementia signs
      on Montreal Cognitive Assessment (MoCA). Computerized battery of Central Nervous
      System Vital Signs (CNS VS) test was used to diagnostic cognitive functions. APOE
      genotype was performed by multiplex PCR. Statistical analysis was performed using
      two-way analysis of variance in STATISTICA software. RESULTS & CONCLUSION: The
      women after menopause have reduced neurocognitive index (NCI) and cognitive
      functions. NCI and all studied cognitive functions of the patients depended
      significantly on APOE polymorphisms. The presence of APOE4 corresponded with
      decreased cognitive functions as opposed to APOE2 which was present in women with
      better level of cognitive functions. Constantly using EPT correlated with three
      cognitive functions: memory, verbal memory and processing speed, which were
      significantly worse for women taking EPT than not taking ones. The interaction
      between APOE polymorphisms and EPT application was significant only for
      processing speed. EPT applying women with epsilon2/epsilon3 and epsilon4 obtained
      better scores in processing speed than women not taking EPT with these APOE
      polymorphisms. The opposite situation concerned women with epsilon3/epsilon3,
      women taking EPT achieved worse processing scores in comparison with those not
      taking EPT. It should be noted that APOE polymorphism assessment may be a factor
      in predicting the effect of EPT on cognitive functioning in postmenopausal
      period.

PMID- 24464002
TI  - Dexamethasone decreases insulin-like growth factor-I and -II via a glucocorticoid
      receptor dependent mechanism in developing rat brain.
AB  - OBJECTIVES: Dexamethasone (Dex) causes neurodegeneration in developing brain.
      Insulin-like growth factor-I (IGF-I) and -II (IGF-II) are potent neurotrophic and
      differentiation factors and play key roles in the regulation of growth and
      development of CNS. Current project evaluated the effects of Dex on IGF-I and -II
      in developing rat brains. MATERIAL AND METHODS: Sprague-Dawley rat pups in each
      litter were divided into vehicle (n=230) or Dex-treated (n=234) groups. Rat pups
      in the Dex group received one of the 3 different regimens of i.p. Dex: tapering
      doses (DexTD) on postnatal days (PD) 3 to PD 6 or repeated doses on PD 4 to PD 6
      or single dose on PD 6. To quantify the glucocorticoid receptor (GR) blockade
      effect, rat pups in the DexTD group on PD 3 and 5 received vehicle or RU486 (GR
      blocker, 60 mg/kg) s.c., twenty minutes prior to Dex treatment. RESULTS: Dex
      decreased the gain of body and brain weight while RU486 inhibited these effects.
      RU486 also prevented the DexTD-induced increase in caspase-3 activity and
      reduction in IGF-I and -II proteins. Compared to the vehicle, the expression of
      mRNA of IGF-I and -II decreased at 24 h after DexTD treatment, while RU486
      prevented this decrease on IGF-II but not IGF-I. CONCLUSIONS: Our findings
      indicate that Dex via GR decreases IGF-I and -II and causes neurodegeneration in
      the neonatal rat brain.

PMID- 24464003
TI  - Differences in the psychological and hormonal presentation of lean and obese
      patients with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine
      disorders found in women of reproductive age. Differences in hormonal and
      metabolic profiles are observed in groups of patients with normal and elevated
      BMI. Cause of disturbances observed in the two groups of patients with PCOS is
      analyzed. The aim of the study is to assess whether psychological parameters of
      lean and obese patients with PCOS are comparably significantly different and
      whether there is a correlation between these characteristics and the
      concentration of various hormones. PARTICIPANTS AND PROCEDURES: The study
      consisted of 20 patients with diagnosed polycystic ovary syndrome and 20 healthy
      women of similar age. Both groups were stratified according to BMI. Specific
      psychological parameters and hormones were estimated in all patients. RESULTS: In
      our study, we found that patients with BMI <25 represented personality traits
      associated with lower resistance to stress. We also observed significantly higher
      ACTH levels in the same group as compared to patients with BMI >25. A correlation
      between plasma ghrelin and the severity of anxiety experienced by test subjects
      was also observed. CONCLUSION: The type of personality and emotional disorders in
      lean PCOS patients may lead to the activation of the hypothalamic-pituitary
      adrenal (HPA) axis and disturbences in hypothalamic-pituitary-ovary (HPO) axis.
      The results suggest participation of primary hypothalamic dysfunction in the
      pathogenesis of PCOS in patients with specific fenotype. Ghrelin is a hormone
      that may affect the symptoms of PCOS in lean patients. Psychological therapy
      should be considered as a permanent element in the therapeutic plan provided to
      PCOS patients.

PMID- 24464004
TI  - Ethical reflection and psychotherapy.
AB  - OBJECTIVE: Theories of ethics and ethical reflection may be applied to both
      theory and practice in psychotherapy. There is a natural affinity between ethics
      and psychotherapy. Psychotherapy practice is concerned with human problems,
      dilemmas and emotions related to both one's own and other people's values. Ethics
      is also concerned with dilemmas in human thinking and with how these dilemmas
      reflect other individuals' values. Philosophical reflection itself is not a
      sufficient basis for the ethics of psychotherapy but it may aid in exploring
      attitudes related to psychotherapy, psychiatry and health care. METHODS: PubMed,
      Web of Science and Scopus databases were searched for articles containing the
      keywords "psychotherapy", "ethics", "therapeutic relationship" and "supervision".
      The search was conducted by repeating the terms in various combinations without
      language or time restrictions. Also included were data from monographs cited in
      reviews. The resulting text is a review with conclusions concerning ethical
      aspects of psychotherapy. RESULTS: The ability to behave altruistically, sense
      for justice and reciprocity and mutual help are likely to be genetically
      determined as dispositions to be later developed by upbringing or to be formed or
      deformed by upbringing. Early experiences lead to formation of ethical attitudes
      which are internalized and then applied to both one's own and other people's
      behavior. Altruistic behavior has a strong impact on an individual's health and
      its acceptance may positively influence the pathophysiological mechanisms
      underlying numerous diseases. Ethical theory and reflection, however, may be
      applied to both theory and practice of psychotherapy in a conscious, targeted and
      thoughtful manner. In everyday practice, psychotherapists and organizations must
      necessarily deal with conscious conflicts between therapeutic possibilities,
      clients' wishes, their own as well as clients' ideas and the real world.
      Understanding one's own motives in therapy is one of the aims of a
      psychotherapist's personal therapy and a frequent goal of supervision
      interventions. It is a psychotherapist's ethical obligation to do no harm,
      maintain clear therapeutic borders, not abuse patients, undertake supervision and
      learn good self-reflection. CONCLUSION: Knowledge of ethical questions and
      related issues as well as continuous ethical self-reflection are essential
      components of high-quality psychotherapeutic management. This requires both good
      psychotherapy training and systematic supervision.

PMID- 24464005
TI  - Evaluation of the safety and efficacy of the first-line treatment with
      somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of
      cyclophosphamide in 20 cases of breast cancer: a preliminary report.
AB  - OBJECTIVE: The current strategies for the treatment of breast cancer are
      essentially based on surgery, preceded and/or followed by chemotherapy often
      supplemented by radiotherapy and/or the administration of hormonal therapy and
      monoclonal antibodies. Their combined use has made it possible to increase an
      overall survival but they are still penalized by adverse effects and toxicity.
      The marked anti-cancer effects of biological molecule such as somatostatin,
      melatonin, retinoid, vitamin D3 and prolactin inhibitors have been studied and
      documented for several decades. Their integrated and synergic action have been
      demonstrated, but only a few studies have as yet been carried out on their
      combined application in humans. The aim of the present investigation was to
      evaluate both the objective clinical response and toxicity of the biological
      multimodal treatment named Di Bella Method (DBM). MATERIAL AND METHODS: The
      clinical data from a total of 20 women with a certified diagnosis of breast
      cancer,defined disease stage, and who independently decided to follow the DBM as
      first-line treatment, were retrospectively reviewed. RESULTS: The mean age of the
      patients was 51 years (min 30; max 73). Twelve (12) patients (60%) presented an
      early stage disease, while the other 40% had a locally advanced/metastatic stage.
      An overall clinical benefit was achieved in 75% of cases, with 55% of complete
      response and 20% of partial response. For metastatic patients, the overall
      survival rate was 71%. The main toxicity effects included leukopenia,
      gastrointestinal phenomena and drowsiness. CONCLUSIONS: The preliminary results
      of this report confirm the positive action of the biological treatment in terms
      of efficacy and survival, showing a more than favorable profile of tolerability.

PMID- 24464006
TI  - Hypermethylation of selected genes in endometrial carcinogenesis.
AB  - OBJECTIVES: Endometrial cancer is one of the most common malignancies in women.
      The prevention has failed so far to develop an effective screening program and
      its incidence is rising in proportion to the incidence of cervical cancer. In
      recent years the investigation of malignancy genomics (genetic and epigenetic
      changes) has become the main focus of scientists because of its high sensitivity
      and specificity. MATERIAL AND METHODS: We conducted a prospective longitudinal
      study at the Dpt. of Gynaecology and Obstetrics of the Jessenius Faculty of
      Medicine in Martin from 2010 to 2012, in collaboration with the Institute of
      Pathology of the University Hospital in Martin. We analysed paraffin blocks of
      endometrial tissue from 123 women with endometrial cancer, hyperplasia and normal
      endometrial findings. By the use of bisulphidic modification technique and nested
      methylation-specific PCR (MSP), we analysed the methylation patterns of three
      genes: GSTP1, E-cad, RASSF1. RESULTS: We found a statistically significant
      increase of methylation of the RASSF1 gene in endometrial cancer compared to
      simplex hyperplasia and intact endometrial tissue (p<0.001). GSTP1 and E-cad did
      not show any relevant methylation pattern in various endometrial lesions.
      CONCLUSION: According to the results of our study, RASSF1 gene methylation could
      serve as a prognostic factor of endometrial carcinogenesis and could help to
      predict the behaviour of endometrial hyperplasia.

PMID- 24464007
TI  - Lithium and valproate acid protect NSC34 cells from H2O2-induced oxidative stress
      and upregulate expressions of SIRT3 and CARM1.
AB  - OBJECTIVE: Lithium and valproic acid (VPA) have been reported to produce
      antioxidant effects by increasing the transcriptional coactivator peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha)
      expression, which may contribute to their neuroprotective properties. As a
      coactivator for many transcriptional factors including PGC-1alpha, coactivator
      associated arginine methyltransferase1(CARM1) regulates oxidative metabolism and
      mitochondrial biogenesis. Besides, Sirtuin3 (SIRT3), a new target of PGC-1alpha,
      plays an important role in preserving mitochondrial function. RESULTS: Here we
      found that protein levels of SIRT3 and CARM1 were decreased during oxidative
      stress in motor neuronal cells (NSC34). Pretreatment of NSC34 cells with lithium
      (5 mmol/L), VPA (1 mmol/L), or lithium plus VPA for 24 hours, significantly
      reduced hydrogen peroxide (H2O2)-induced cytotoxicity, and increased SIRT3 and
      CARM1 levels. CONCLUSION: Our results suggest that lithium and VPA may decrease
      vulnerability of motor neuronal cells to cellular injury evoked by oxidative
      stress, which possibly arising from putative mitochondrial disturbances. And
      further study of the molecular mechanisms of SIRT3 and CARM1 regulation may
      provide a novel target for treating motor neuron disease.

PMID- 24464008
TI  - Maternal infanticide and low maternal ability in cerebellar mutants Lurcher.
AB  - OBJECTIVE: One of the common, but less studied deficiencies in mouse models of
      cerebellar disorders is impaired breeding capacity. Nevertheless, there is no
      extensive study in Lurcher (Grid2Lc) mice, a model of olivocerebellar
      degeneration. The aim of this work was to analyze a breeding capacity of these
      mutants. METHODS: Lurcher females mated with healthy wild type males were
      compared with two control groups: wild type females mated with wild type males
      and wild type females mated with Lurcher males. The breeding capacity of Lurcher
      mice was analyzed using a fertility rate, mating capability and pups survival
      rate through three consecutive litters. RESULTS: Lurcher dams did not show
      significantly reduced fertility and mating capability. Nevertheless, their
      breeding capacity was affected by reduced litter size, maternal infanticide and
      higher pup mortality during the maternal care period. CONCLUSION: Lurcher mice
      are fertile and mating capable cerebellar mutants, but their breeding capacity is
      reduced due to the postpartum behavioral abnormalities. With regard to hyper
      reactivity of the hypothalamo-pituitary-adrenal axis followed by behavioral
      disinhibition during stressful events in Lurcher mutants, we hypothesize that the
      lower breeding capacity is associated with these endocrine and behavioral
      abnormalities.

PMID- 24464009
TI  - Neck nodular lesions mimicking thyroid tumors.
AB  - OBJECTIVE: Neck nodular lesions may derive from several different tissues, often
      mimicking thyroid tumor in the preoperative examination. METHODS: We described
      three patients admitted in 2012 to the Department of Endocrine Surgery in Wroclaw
      with nodular lesion in the neck area mimicking tumor of the thyroid gland.
      RESULTS: In the first patient with a tumor in projection on the isthmus and the
      left thyroid lobe, neurilemmoma was discovered in the histopathological exams. In
      the second one with the suspicion of papillary thyroid carcinoma, adenoid cyst
      carcinoma was identified in the pathological examination. In the third case,
      suspected to being a recurrent or split goiter, non-specific, chronic
      lymphonodulitis was recognized in the final histology. CONCLUSIONS: Appropriate
      and careful diagnostics of a nodular lesion in the neck before surgery has
      crucial significance for choosing optimal method of surgical treatment which has
      great influence on mortality rate and reducing complications.

PMID- 24464010
TI  - Parathyroid adenoma diagnosed on the basis of a giant cell tumor of parieto
      occipital region and multifocal bone injuries.
AB  - Brown tumors are rare skeletal manifestations of hyperparathyroidism (HPT) that
      may mimic cancer metastases. Histopathologically, they are difficult to
      differentiate from other giant cell lesions. A case is presented of 41-year-old
      woman with giant cell tumor in parieto-occipital region with injury of external
      bone lamina, growing into the skull cavity. The mass was suspected of being
      neoplastic. Numerous osteolytic lesions in the skull skeleton and multifocal bone
      injuries were observed, also. Elevation in calcium (5.91 mEq/L) and parathormone
      (1188 ng/mL) concentrations and hypercalciuria (52 mEq/24 h) suggested the
      diagnosis of HPT initially manifesting as a brown tumor of the skull. Further
      exploration confirmed the existence of parathyroid adenoma as a cause of the
      disease. The key treatment for the condition was surgical excision of the adenoma
      followed by the normalization of parathyroid function and significant reduction
      in size of skull tumor and other lesions. 

PMID- 24464011
TI  - Pre-activation and muscle activity during frontal impact in relation to whiplash
      associated disorders.
AB  - OBJECTIVE: For the evaluation of neck injury the relative distance was observed
      between a marker placed on the forehead and a marker placed on the shoulder and
      also by change of the angle. To compare the severity of head injury a value of
      maximum head acceleration was used, HIC and a 3 ms criterion. All criteria were
      related to the activity of musculus sternocleidomastoideus and musculus trapezius
      in a situation of expected or unexpected impact. MATERIALS AND METHODS: The
      situation was recorded using a Qualisys system, head acceleration of probands in
      three axes was recorded using the accelerometer, activity of neck muscles was
      monitored by a mobile EMG. RESULTS: Maximum head acceleration was 12.1 g for non
      visual and 8.2 g for visual. HIC36 was 5.7 non visual and 4.0 for visual. 3-ms
      criterion was 11.5 g for non-visual and 7.8 g for visual. The average time of
      muscle activation of the observed group without visual perception is 0.027 s
      after hitting an obstacle, with visual perception 0.127 s before the crash.
      CONCLUSIONS: Kinematic values indicate more favourable parameters for neck
      injuries for visual. Head injury criteria show an average decrease of about 30%
      for visual. We can conclude that the visual perception means a significant
      increase in pre-activation of the observed muscle group of almost 400% and lower
      activation in both following phases of approximately 40%.

PMID- 24464012
TI  - Preliminary report of 48-hours Atosiban administration in spontaneous preterm
      labor - Doppler blood flow assessment of placental and fetal circulation.
AB  - OBJECTIVES: The aims were to investigate whether there are any changes in
      placental and fetal circulation during Atosiban tocolysis within the first 48
      hours of therapy. METHODS: Detailed Doppler evaluation of placental and fetal
      circulation was performed prior to Atosiban administration and thereafter at 24
      and 48 hours. Maternal heart rate and the pulsatility index (PI) in both uterine
      arteries (R-UtA, L-UtA) were assessed. Fetal heart rate (FHR), the resistance
      (RI) and pulsatility index (PI) of umbilical (UA) and middle cerebral artery
      (MCA) were measured. Additionally cerebroplacental ratio was calculated. E-wave/A
      wave ratio (E/A) for atrioventricular valves, the myocardial performance index
      (MPI) and shortening fraction (SF) for both ventricles were calculated for both
      ventricles independently. To determine changes over time in all study variables
      analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's
      post hoc test was used. The effects of additional clinical covariates were
      checked. RESULTS: Maternal heart rate and blood flow in (R-UtA/L-UtA) were not
      altered significantly during Atosiban administration. No significant changes in
      FHR as well as Doppler parameters (RI, PI, PSV) in UA and MCA were recorded after
      24/48 hours of tocolytic treatment. The mean values of cerebroplacental ratio
      (CPR) remained unaltered during treatment. Detailed evaluation of fetal cardiac
      function parameters (E/A, SF, MPI) calculated independently for both ventricles,
      revealed no significant changes over the time. CONCLUSIONS: To our best knowledge
      this study has been first evaluation of placental and fetal circulation with
      assessment of cardiac hemodynamic function during 48-hours administration of
      Atosiban. This kind of tocolysis treatment seems not to alter uterine nor fetal
      arterial blood flow pattern seriously. Hemodynamic cardiac activity in fetuses
      has remained unaffected. We cannot conclude definitely that there are absolutely
      no changes in the fetal hemodynamic condition due to Atosiban. Further studies
      should be performed to verify its possible influence on fetal venous blood flow.

PMID- 24464013
TI  - Proteomic analysis of eutopic and ectopic endometriotic tissues based on isobaric
      peptide tags for relative and absolute quantification (iTRAQ) method.
AB  - OBJECTIVE: The present study aimed at performing proteomic analysis of matched
      eutopic endometrium and ovarian endometrioid cysts from women with endometriosis
      in order to discover any abnormal protein expression related to the disease.
      DESIGN AND SETTING: The study included 8 women with stage III/IV endometriosis
      according to revised American Fertility Society (rAFS) classification and one
      woman with no signs of the disease as a reference. Proteomic analysis was
      performed using a novel isobaric tag-based methodology for relative and absolute
      peptide quantification (iTRAQ) coupled with multidimensional liquid
      chromatography and tandem mass spectrometry. RESULTS: The selection of 419
      proteins was found in all endometriosis specimens. Using normal eutopic
      endometrium from woman without endometriosis as a reference, some proteins
      expressions were significantly increased in all endometriosis samples. They
      included collagen alpha1(XIV), calmodulin, collagen alpha(VI), plexin, integrin
      alphaVbeta3, transgelin, desmin, and vimentin. The comparison of these proteins'
      expression in paired eutopic and ovarian endometriosis samples has revealed that
      only vimentin was significantly increased in ovarian endometrioma. CONCLUSIONS:
      It was confirmed that endometriosis is associated with different expression of
      proteins in endometriotic samples. Nevertheless, further studies seem to be
      necessary as they may reveal possible markers that would be useful in clinical
      diagnosis of the disease.

PMID- 24464014
TI  - The occurrence of immunological disturbances in patients with recurrent
      miscarriage (RM) of unknown etiology.
AB  - OBJECTIVE: The 155 patients suffering from primary RM who took part in this study
      were qualified after excluding known causes of abortions. METHODS: The presence
      of the following immunological factors was examined in serum samples:
      autoantibodies such as anti-cardiolipin (ACA) IgG and IgM, lupus-anticoagulant
      (LA), anti-thyroid (ATA): anti-thyroglobulin (anti-TG) and anti-thyroid
      peroxydase (anti-TPO), anti-nuclear (ANA), anti-placental (APA) antibodies and
      alloimmunological disturbances following HLA-class I antibody test (LCT
      lymphocytotoxic test), lack of blocking proliferative activity in mixed
      lymphocyte reaction test (MLR), anti-sperm (ASA) antibodies, levels of
      extracellular interferon gamma (IFN gamma) and tumour necrosis alpha (TNFalpha)
      produced by peripheral blood lymphocytes. RESULTS: Immunological disturbances
      were found in 69.1% of the patients suffering from primary RM of unknown
      etiology. The number of RM correlated with the frequency of immunological
      disturbance. Among the samples from patients who underwent >=5 RM, positive
      levels of TNFalpha were the most frequently observed risk factor (up to 27%)
      (p=0.05). Although the incidence of immunological factors was comparable between
      patients with early and late pregnancy losses, elevated ATA levels were
      frequently seen among late miscarriage (95% CI=36.0, p<=0.01). CONCLUSION: The
      heterogeneity of immunological risk factors shown in this study indicates the
      usefulness of detecting alloimmune factors as well as autoantibodies in patients
      with RM of unknown etiology. This may be helpful to analyse the therapeutical
      effectivity of various treatment in a better characterized group of patients and
      to explain unsuccessful results of treatment in patients with RM of unknown
      etiology.

PMID- 24464015
TI  - IKK-dependent activation of NF-kappaB contributes to myeloid and lymphoid
      leukemogenesis by BCR-ABL1.
AB  - The product of the Ph chromosome, the BCR-ABL1 tyrosine kinase activates diverse
      signaling pathways in leukemic cells from patients with chronic myeloid leukemia
      (CML) and Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). Previous studies
      showed that nuclear factor kappaB (NF-kappaB) is activated in BCR-ABL1-expressing
      cells, but the mechanism of activation and importance of NF-kappaB to the
      pathogenesis of BCR-ABL1-positive myeloid and lymphoid leukemias are unknown.
      Coexpression of BCR-ABL1 and a superrepressor mutant of inhibitory NF-kappaB
      alpha (IkappaBalphaSR) blocked nuclear p65/RelA expression and inhibited the
      proliferation of Ba/F3 cells and primary BCR-ABL1-transformed B lymphoblasts
      without affecting cell survival. In retroviral mouse models of CML and B-ALL,
      coexpression of IkappaBalphaSR attenuated leukemogenesis, prolonged survival, and
      reduced myeloid leukemic stem cells. Coexpression of dominant-negative mutants of
      IkappaB kinase alpha (IKKalpha)/IKK1 or IKKbeta/IKK2 also inhibited lymphoid and
      myeloid leukemogenesis by BCR-ABL1. Blockade of NF-kappaB decreased expression of
      the NF-kappaB targets c-MYC and BCL-X and increased the sensitivity of BCR-ABL1
      transformed lymphoblasts to ABL1 kinase inhibitors. These results demonstrate
      that NF-kappaB is activated through the canonical IKK pathway and plays distinct
      roles in the pathogenesis of myeloid and lymphoid leukemias induced by BCR-ABL1,
      validating NF-kappaB and IKKs as targets for therapy of Ph(+) leukemias.

PMID- 24464016
TI  - Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B
      cells that are highly dependent on the microenvironment for maintenance and
      expansion. However, little is known regarding the mechanisms whereby CLL cells
      create their favorable microenvironment for survival. High-mobility group protein
      B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted
      by innate immune cells and passively released by injured or dying cells. We found
      significantly increased HMGB1 levels in the plasma of CLL patients compared with
      healthy controls, and HMGB1 concentration is associated with absolute lymphocyte
      count. We therefore sought to determine potential roles of HMGB1 in modulating
      the CLL microenvironment. CLL cells passively released HMGB1, and the timing and
      concentrations of HMGB1 in the medium were associated with differentiation of
      nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the
      markers for NLCs, was associated with shorter overall survival of CLL patients.
      HMGB1-mediated NLC differentiation involved internalization of both receptor for
      advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9).
      Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway.
      In conclusion, this study demonstrates for the first time that CLL cells might
      modulate their microenvironment by releasing HMGB1. 

PMID- 24464018
TI  - Atypical femoral fractures after anti-osteoporotic medication: a Korean
      multicenter study.
AB  - PURPOSE: Increasing numbers of atypical femoral fractures have been reported
      among long-term bisphosphonate users. We evaluated clinical characteristics of
      atypical femoral fractures throughout Korean multicenter studies. METHODS: We
      retrospectively analysed the bone mineral density, prodromal symptoms before
      femoral fracture, and medication history of osteoporosis in 76 cases of atypical
      femoral fracture. RESULTS: The mean age of cases was 71.4 +/- 8.8 (range, 43-89)
      years old. The mean follow-up period after the fracture operation was 24.5 +/-
      12.9 (range, 12-79) months. BMI was 23.2 +/- 3.0 on average. The mean BMD of
      femur was -1.9 +/- 1.4 (range, -4.8 to 1.3). Prodromal symptoms including thigh
      pain before femoral fracture appeared in 22 (28.9 %) of 76 patients. All patients
      included in the study used bisphosphonate. The duration of taking bisphosphonate
      before fracture was 36.8 +/- 50.8 (one-204 months) months. Fifty-seven (75 %) of
      76 patients were taking the medication for more than three years. Delayed union
      occurred in 43 (56.5 %) of 76 patients. Delayed union was defined as a fractured
      bone that did not completely heal within six months of injury. The group of
      having taken anti-osteoporotic medication for more than three years showed
      relatively longer union period compared to that for a shorter period medication
      group (4.8 +/- 2.5 months vs 9.3 +/- 3.7 months, p = 0.017). The delayed union
      developed in 43 (56.5 %) of 76 patients and showed a significantly higher
      incidence in the group with long-term therapy (five/43 vs 38/43, p = 0.021). The
      bilateral femoral fractures developed in 23 (30.2 %) of 76 patients and showed a
      high incidence in the group medicated more than three years (two/23 vs 21/23, p =
      0.039). CONCLUSIONS: The longer bisphosphonates are used, the more the cases of
      delayed union and the more frequent the development of bilateral fractures
      following unilateral fractures. With regard to the delayed union, the methods of
      the acceleration of fracture healing may be beneficial in atypical femoral
      fracture patients who had been receiving long-term bisphosphonates therapy.
      Careful observation is required for contra-lateral femurs due to a high incidence
      of bilateral atypical femoral fractures.

PMID- 24464019
TI  - Thyroid: biological actions of 'nonclassical' thyroid hormones.
AB  - Thyroid hormones (THs) are produced by the thyroid gland and converted in
      peripheral organs by deiodinases. THs regulate cell functions through two
      distinct mechanisms: genomic (nuclear) and nongenomic (non-nuclear). Many TH
      effects are mediated by the genomic pathway--a mechanism that requires TH
      activation of nuclear thyroid hormone receptors. The overall nongenomic
      processes, emerging as important accessory mechanisms in TH actions, have been
      observed at the plasma membrane, in the cytoplasm and cytoskeleton, and in
      organelles. Some products of peripheral TH metabolism (besides triiodo-L
      thyronine), now termed 'nonclassical THs', were previously considered as inactive
      breakdown products. However, several reports have recently shown that they may
      have relevant biological effects. The recent accumulation of knowledge on how
      classical and nonclassical THs modulate the activity of membrane receptors,
      components of the mitochondrial respiratory chain, kinases and deacetylases,
      opened the door to the discovery of new pathways through which they act. We
      reviewed the current state-of-the-art on the actions of the nonclassical THs,
      discussing the role that these endogenous TH metabolites may have in the
      modulation of thyroid-related effects in organisms with differing complexity,
      ranging from nonmammals to humans.

PMID- 24464017
TI  - Two-stage treatment of infected total knee arthroplasty: two to thirteen year
      experience using an articulating preformed spacer.
AB  - PURPOSE: Infection following knee replacement is an important cause of failure
      despite rigorous prophylaxis antibiotic protocols. The two-stage reimplantation
      procedure is considered the gold standard for treatment of subacute and chronic
      deep periprosthetic infections. The purpose of this study was to determine
      whether or not a preformed articulated spacer would allow comparable eradication
      of infection equal to rates reported in published studies and to see whether
      there is a resulting improvement in postoperative function with an acceptable
      quality of life, reducing postoperative pain and limiting surgical complications,
      thus simplifying the second stage of the procedure. METHODS: We retrospectively
      reviewed 50 patients with infected TKA who underwent a two-stage exchange
      arthroplasty using an articulating preformed spacer. The device, designed like an
      ultracongruent condylar knee prosthesis, is composed of acrylic cement
      impregnated with antibiotic, with tested and standardised mechanical properties
      and antibiotic content and release mechanism. RESULTS: The median follow-up
      period was seven (two to 13) years. Two-stage exchange arthroplasty was
      successful in controlling the infection in 92% of patients; 64% of patients where
      women, and median patient age was 68 (54-80) years. Median implantation time of
      the preformed spacer was 16 (four to 60) weeks; 4% of infections were delayed,
      and 96% were late. Forty-six percent were caused by coagulase-negative
      Staphylococcus (CoNS). Mean Knee Society Score (KSS) was 35.38 (clinical) and
      37.96 (function) on presentation; it improved to a mean of 72.92 (clinical) and
      76.04 (function) after the first stage and to a mean of 75.38 (clinical) and
      80.58 (function) at the final review. Bone loss was unchanged between stages, and
      range of motion remained unchanged or improved after definitive reimplantation.
      CONCLUSION: The use of preformed articulated knee spacer during a two stage
      technique for infected TKA improves patient QOL between stages and increases
      patient compliance and cooperation, reducing social costs.

PMID- 24464020
TI  - The role of adiponectin in renal physiology and development of albuminuria.
AB  - Adiponectin is secreted by the adipose tissue and is downregulated in states of
      obesity and insulin resistance. There is a growing body of evidence indicating
      that adiponectin has renoprotective effects and protects against the development
      of albuminuria in rodent experiments. Adiponectin crossing the glomerular
      filtration barrier possibly inhibits inflammation, fibrosis and oxidative stress
      in kidneys through activation of AMP-activated protein kinase. Moreover,
      microalbuminuria is a well established early sign of progressive cardiovascular
      and renal disease, even in subjects with preserved glomerular filtration rate.
      Studies investigating the relationship between serum adiponectin levels and
      urinary albumin excretion rate (UAE) have yielded conflicting data and the
      mechanisms underlying the interplay between adiponectin and albuminuria remain to
      be elucidated. This article constitutes a critical review attempting to clarify
      any remaining confusion about this matter. Furthermore, this article examines the
      clinical significance of adiponectin-albuminuria interplay, suggesting that
      adiponectin is possibly involved in the development of albuminuria that is
      associated with obesity, diabetes and cardiovascular disease and may mediate, at
      least in part, the actions of medical treatments that influence UAE, such as
      angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers,
      thiazolidinediones, fenofibrate and diet. Further studies to investigate more
      thoroughly the renoprotective role of adiponectin in the human setting should be
      carefully planned, focusing on causality and the possible influence of
      adiponectin on the development of albuminuria in specific clinical settings. 

PMID- 24464021
TI  - Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared
      fasted adult rats.
AB  - Neuroendocrine axes adapt to nutrient availability. During fasting, the function
      of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the
      hypothalamus-pituitary-adrenal axis (HPA) is increased. Overfeeding-induced
      hyperleptinemia during lactation may alter the regulatory set point of
      neuroendocrine axes and their adaptability to fasting in adulthood.
      Hyperleptinemia is developed in rodents by litter size reduction during
      lactation; adult rats from small litters become overweight, but their
      paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether
      peptide expression still responds to nutrient availability. PVN corticotropin
      releasing factor (CRF) expression has not been evaluated in this model. We
      analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of
      reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (early
      overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of
      animals from each group was fasted for 48 h and leptin, corticosterone, and
      thyroid hormones serum levels were analyzed. In brain, expressions of leptin
      receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH
      and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN
      subcompartments was assayed by in situ hybridization. Early-overfed adults
      developed hyperphagia and excessive weight, together with decreased proTRH
      expression in anterior PVN, supporting the anorexigenic effects of TRH. Early
      overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a
      further reduction. Fasting-induced stress was unable to increase corticosterone
      levels, contributing to reduced body weight loss in early-overfed rats. We
      concluded that early overfeeding impaired the adaptability of HPT and HPA axes to
      excess weight and fasting in adults. 

PMID- 24464022
TI  - Increased glucocorticoid activation during mouse skin wound healing.
AB  - Glucocorticoid (GC) excess inhibits wound healing causing increased patient
      discomfort and infection risk. 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in
      rodents) in many tissues including skin, where de novo steroidogenesis from
      cholesterol has also been reported. To examine the regulation of 11beta-HSD1 and
      steroidogenic enzyme expression during wound healing, 5 mm wounds were generated
      in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to
      unwounded skin. 11beta-HSD1 expression (mRNA and protein) and enzyme activity
      were elevated at 2 and 4 days post-wounding, with 11beta-HSD1 localizing to
      infiltrating inflammatory cells. 11beta-HSD2 (GC-deactivating) mRNA expression
      and activity were undetectable. Although several steroidogenic enzymes displayed
      variable expression during healing, expression of the final enzyme required for
      the conversion of 11-deoxycorticosterone to corticosterone, 11beta-hydroxylase
      (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11
      deoxycorticosterone was the principal progesterone metabolite in mouse skin
      before and after wounding. Our findings demonstrate that 11beta-HSD1 activates
      considerably more corticosterone than is generated de novo from progesterone in
      mouse skin and drives GC exposure during healing, demonstrating the basis for
      11beta-HSD1 inhibitors to accelerate wound repair. 

PMID- 24464023
TI  - The potential role of VEGF-induced vascularisation in the bony repair of injured
      growth plate cartilage.
AB  - Growth plate injuries often result in undesirable bony repair causing bone growth
      defects, for which the underlying mechanisms are unclear. Whilst the key
      importance of pro-angiogenic vascular endothelial growth factor (VEGF) is well
      known in bone development and fracture repair, its role during growth plate bony
      repair remains unexplored. Using a rat tibial growth plate injury repair model
      with anti-VEGF antibody, Bevacizumab, as a single i.p. injection (2.5 mg/kg)
      after injury, this study examined the roles of VEGF-driven angiogenesis during
      growth plate bony repair. Histology analyses observed isolectin-B4-positive
      endothelial cells and blood vessel-like structures within the injury site on days
      6 and 14, with anti-VEGF treatment significantly decreasing blood-vessel-like
      structures within the injury site (P<0.05). Compared with untreated controls,
      anti-VEGF treatment resulted in an increase in undifferentiated mesenchymal
      repair tissue, but decreased bony tissue at the injury site at day 14 (P<0.01).
      Consistently, microcomputed tomography analysis of the injury site showed
      significantly decreased bony repair tissue after treatment (P<0.01). RT-PCR
      analyses revealed a significant decrease in osteocalcin (P<0.01) and a decreasing
      trend in Runx2 expression at the injury site following treatment. Furthermore,
      growth plate injury-induced reduced tibial lengthening was more pronounced in
      anti-VEGF-treated injured rats on day 60, consistent with the observation of a
      significantly increased height of the hypertrophic zone adjacent to the growth
      plate injury site (P<0.05). These results indicate that VEGF is important for
      angiogenesis and formation of bony repair tissue at the growth plate injury site
      as well as for endochondral bone lengthening function of the uninjured growth
      plate. 

PMID- 24464024
TI  - Dynamics of insulin-like factor 3 and its receptor expression in boar testes.
AB  - Relaxin-like factor (RLF), now mainly known as insulin-like factor 3 (INSL3), is
      essential for testis descent during fetal development; however, its function in
      the adult testis is still being elucidated. As a major step toward understanding
      the as-yet-unknown function of INSL3 in boars, this study aimed to develop a time
      resolved fluoroimmunoassay for boar INSL3, characterize the dynamics of INSL3
      expression during development, and demonstrate the expression of the INSL3
      hormone-receptor system in the testis. All samples were collected from Duroc
      boars. The sensitivity of the assay system established was 8.2 pg/well (164
      pg/ml), and no cross-reactivity with other hormones, such as porcine relaxin, was
      observed. Circulating INSL3 was shown to increase progressively during
      development. INSL3 secreted from the Leydig cells was released not only into the
      blood circulation but also into the interstitial and seminiferous compartments in
      sufficient concentrations. A testicular fractionation study revealed that its
      receptor RXFP2 transcripts were expressed mainly in testicular germ cells. In
      addition, INSL3 bound to the germ cell membranes in a hormone-specific and
      saturable manner. These results reveal that INSL3 secreted into the interstitial
      compartment from the Leydig cells is transported into the seminiferous
      compartments, where its receptor RXFP2 is expressed mainly in the germ cells to
      which INSL3 binds, suggesting that INSL3 functions as a paracrine factor on
      seminiferous germ cells. 

PMID- 24464025
TI  - Combined effects of working hours, income, and leisure time on suicide in all 47
      prefectures of Japan.
AB  - This study describes an ecological study that evaluated the combined effects of
      working hours, income, and leisure time on suicide in all 47 prefectures of
      Japan. In men, the age-adjusted rate of suicide (per 100,000 population) was
      significantly correlated with working hours (r=0.587, p<0.0001) as well as
      significantly and negatively correlated with income (r=-0.517, p=0.0002) and
      times for the leisure activities of self-education (r=-0.447, p=0.0016) and
      hobbies (r=-0.511, p=0.0002). In addition, a stepwise multiple regression
      analysis identified time for leisure social activities as a determining factor in
      suicide rate, even after adjusting for working hours and income. However, the
      impact of time for leisure social activities on suicide rate was smaller than
      that of working hours and income. In contrast, none of these factors affected
      suicide rate in women. These results suggest that increasing leisure time may be
      useful for preventing suicide among men in Japan. 

PMID- 24464026
TI  - Serum levels of TGF-beta1 and MCP-1 as biomarkers for progressive coal workers'
      pneumoconiosis in retired coal workers: a three-year follow-up study.
AB  - Various cytokines activated by the inhalation of coal dust may mediate
      inflammation and lead to tissue damage. Objective of this study was to examine
      the relationships between coal workers' pneumoconiosis (CWP) progression over a 3
      yr period and the serum levels of cytokines in 85 retired coal workers. To
      investigate the relevance of serum cytokines in CWP, serum levels of interleukin
      8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor
      beta1 (TGF-beta1), and monocyte chemotactic protein-1 (MCP-1) as progressive CWP
      biomarkers were studied in relation to the progression of pneumoconiosis over a 3
      yr period in 85 patients with CWP. CWP progression was evaluated through paired
      comparisons of chest radiographs. Median levels of TGF-beta1 and MCP-1 were
      significantly higher in subjects with progressive CWP than in those without CWP
      progression. The area under the ROC curve for TGF-beta1 (0.693) and MCP-1 (0.653)
      indicated that these cytokines could serve as biomarkers for the progression of
      CWP. Serum TGF-beta1 levels were related to the progression of CWP (beta=0.247,
      p=0.016). The results suggest that high serum levels of TGF-beta1 and MCP-1 are
      associated with the progression of CWP. 

PMID- 24464027
TI  - Cyclic peptide analogs of 558-565 epitope of A2 subunit of Factor VIII prolong
      aPTT. Toward a novel synthesis of anticoagulants.
AB  - Novel anticoagulant therapies target specific clotting factors in blood
      coagulation cascade. Inhibition of the blood coagulation through Factor VIII
      Factor IX interaction represents an attractive approach for the treatment and
      prevention of diseases caused by thrombosis. Our research efforts are continued
      by the synthesis and biological evaluation of cyclic, head to tail peptides,
      analogs of the 558-565 sequence of the A2 subunit of FVIII, aiming at the
      efficient inhibition of Factor VIIIa-Factor IXa interaction. The analogs were
      synthesized on solid phase using the acid labile 2-chlorotrityl chloride resin,
      while their anticoagulant activities were examined in vitro by monitoring
      activated partial thromboplastin time and the inhibition of Factor VIII activity.
      The results reveal that these peptides provide bases for the development of new
      anticoagulant agents. 

PMID- 24464028
TI  - In vivo imaging of kidney glomeruli transplanted into the anterior chamber of the
      mouse eye.
AB  - Multiphoton microscopy enables live imaging of the renal glomerulus. However,
      repeated in vivo imaging of the same glomerulus over extended periods of time and
      the study of glomerular function independent of parietal epithelial and proximal
      tubular cell effects has not been possible so far. Here, we report a novel
      approach for non-invasive imaging of acapsular glomeruli transplanted into the
      anterior chamber of the mouse eye. After microinjection, glomeruli were capable
      of engrafting on the highly vascularized iris. Glomerular structure was
      preserved, as demonstrated by podocyte specific expression of cyan fluorescent
      protein and by electron microscopy. Injection of fluorescence-labeled dextrans of
      various molecular weights allowed visualization of glomerular filtration and
      revealed leakage of 70 kDa dextran in an inducible model of proteinuria. Our
      findings demonstrate functionality and long-term survival of glomeruli devoid of
      Bowman's capsule and provide a novel approach for non-invasive longitudinal in
      vivo study of glomerular physiology and pathophysiology.

PMID- 24464029
TI  - Group mental health interventions in civilian populations in war-conflict areas:
      a Lebanese pilot study.
AB  - PURPOSE: Cognitive behavioral (CB) group therapy is an effective therapeutic
      intervention to treat war-related trauma. The aim of this pilot study was to
      describe the effects of conducting CB group therapy in a civilian population
      exposed to war in southern Lebanon. METHOD: Participants presenting with
      psychiatric symptoms attended an 8-week CB group therapy intervention adapted to
      the Lebanese culture. Observations from therapists' field notes were reviewed and
      grouped into commonalities. FINDINGS: A majority of the total participants (N =
      10) reported satisfaction with the CB therapy and a decrease in symptoms. Field
      notes revealed positive group interactions (i.e., sharing information,
      cohesiveness), therapeutic benefits (i.e., symptom identification, destigmatizing
      mental illness, learning coping strategies), and barriers to attendance (i.e.,
      stigma, personal constraints). CONCLUSION AND IMPLICATIONS: CB group therapy is a
      promising intervention for civilian survivors of war trauma. Challenges to
      conducting such interventions in a war-conflict area are discussed. Future
      research and intervention planning should address challenges faced during this
      study to better meet mental health needs.

PMID- 24464030
TI  - How soon should we start interventional feeding in the ICU?
AB  - PURPOSE OF REVIEW: Nutrition in the critically ill patient remains a
      controversial topic. Most clinicians have viewed nutrition as part of patient
      care but not as a therapeutic intervention. Recent studies have looked at type
      and timing of nutrition to determine whether they affect important clinical
      outcomes. RECENT FINDINGS: Large-scale, multicentre randomized trials have found
      that supplemental parenteral nutrition has a deleterious effect in comparison to
      enteral nutrition alone. Use of early parenteral nutrition in critically ill
      patients in whom enteral nutrition was contraindicated did not significantly
      improve clinical outcomes. Also, low-dose or trophic enteral nutrition has
      similar benefits with less gastrointestinal complications compared with early
      full dose caloric feedings. The timing of early nutrition has been defined in
      most large-scale studies as beginning within 48 h of intubation, though some
      earlier studies used a 24-h cut-off point with some improved outcomes. SUMMARY:
      Although not strong, the best available data suggest that critically ill patients
      should be started on enteral tube feeds within 48 h of intubation whenever
      possible. The use of parenteral nutrition should be limited within the first 6
      days, and not used to augment caloric intake. Finally, similar benefits are seen
      in patients receiving minimal enteral feeds versus full caloric enteral
      nutrition.

PMID- 24464031
TI  - Feasibility of Using Distal Endpoints for In-room PET Range Verification of
      Proton Therapy.
AB  - In an effort to verify the dose delivery in proton therapy, Positron Emission
      Tomography (PET) scans have been employed to measure the distribution of beta+
      radioactivity produced from nuclear reactions of the protons with native nuclei.
      Because the dose and PET distributions are difficult to compare directly, the
      range verification is currently carried out by comparing measured and Monte Carlo
      (MC) simulation predicted PET distributions. In order to reduce the reliance on
      MC, simulated PET (simPET) and dose distal endpoints were compared to explore the
      feasibility of using distal endpoints for in-room PET range verification. MC
      simulations were generated for six head and neck patients with corrections for
      radiological decay, biological washout, and PET resolution. One-dimensional
      profiles of the dose and simPET were examined along the direction of the beam and
      covering the cross section of the beam. The chosen endpoints of the simPET (x
      intercept of the linear fit to the distal falloff) and planned dose (20-50% of
      maximum dose) correspond to where most of the protons are below the threshold
      energy for the nuclear reactions. The difference in endpoint range between the
      distal surfaces of the dose and MC-PET were compared and the spread of range
      differences were assessed. Among the six patients, the mean difference between MC
      PET and dose depth was found to be -1.6 mm to +0.5 mm between patients, with a
      standard deviation of 1.1 to 4.0 mm across the individual beams. In clinical
      practice, regions with deviations beyond the safety margin need to be examined
      more closely and can potentially lead to adjustments to the treatment plan.

PMID- 24464032
TI  - miRNAs promote generation of porcine-induced pluripotent stem cells.
AB  - The pigs have similarities of organ size, immunology and physiology with humans.
      Porcine-induced pluripotent stem cells (piPSCs) have great potential application
      in regenerative medicine. Here, we established piPSCs induced from porcine fetal
      fibroblasts by the retroviral overexpression of Oct4, Sox2, Klf4, and c-Myc. The
      piPSCs not only express pluripotent markers but also have the capacity for
      differentiation in vivo and in vitro, including EB and teratoma formation. We
      supplemented microRNAs during the induction process because miR-302a, miR-302b,
      and miR-200c have been reported to be highly expressed in human and mouse
      embryonic stem cells and in iPSCs. In this study, we found that the
      overexpression of miR-302a, miR-302b, and miR-200c effectively improved the
      reprogramming efficiency and reduced the induction time for piPSCs in the OSKM
      and OSK induction systems. Due to the similar induction efficiency of 4F-induced
      piPSCs or of three factors combined with miR-302a, miR-302b, and miR-200c (3F
      miRNA-induced piPSCs), we recommend the addition of miRNAs instead of c-Myc to
      reduce the tumorigenicity of piPSCs. 

PMID- 24464033
TI  - Akt and Erk1/2 activate the ornithine decarboxylase/polyamine system in
      cardioprotective ischemic preconditioning in rats: the role of mitochondrial
      permeability transition pores.
AB  - Ornithine decarboxylase (ODC) is the first rate-limiting enzyme in polyamine
      biosynthesis, which is essential for cell survival. We hypothesized that the
      ODC/polyamine system is involved in ischemic preconditioning (IPC)-mediated
      cardioprotection through the activation of Erk1/2 and Akt and through the
      inhibition of the mitochondrial permeability transition (mPT). Isolated rat
      hearts were subjected to 40 min of ischemia either with or without IPC (3 cycles
      of 5-min global ischemia), and ODC protein expression, polyamine content, and Akt
      and Erk1/2 phosphorylation were evaluated after 30 min of reperfusion. IPC
      significantly upregulated the ODC/polyamine pathway, promoted Erk1/2 and Akt
      phosphorylation, and reduced the infarct size and heart dysfunction after
      reperfusion. An inhibitor of ODC, alpha-difluoromethylornithine (DFMO), abolished
      the IPC-induced cardioprotection. Moreover, the inhibition of the IPC-induced
      activation of Erk1/2 and Akt using PD98059 or wortmannin downregulated the
      ODC/polyamine system. In separate studies, the Ca(2+) load required to open the
      mPT pore was significantly lower in DFMO-treated cardiac mitochondria than in
      mitochondria from IPC hearts. Furthermore, spermine or spermidine significantly
      inhibited the mPT induced by CaCl2. These results suggest that IPC upregulates
      the ODC/polyamine system and mediates preconditioning cardioprotection, which may
      depend on the phosphorylation/activation of Erk1/2 and Akt and on the inhibition
      of the mPT during reperfusion.

PMID- 24464034
TI  - A D-amino acid containing peptide as a potent, noncovalent inhibitor of
      alpha5beta1 integrin in human prostate cancer invasion and lung colonization.
AB  - Primary tumors often give rise to disseminated tumor cells (DTC's), which acquire
      full malignancy after invading distant site(s). Thus, DTC's may be a productive
      target for preventing prostate cancer metastasis progression. Our prior research
      showed that PHSCN peptide (Ac-PHSCN-NH2) targets activated alpha5beta1 integrin
      to prevent invasion and metastasis in preclinical adenocarcinoma models, and
      disease progression in Phase I clinical trial. Here, we report that D
      stereoisomer replacement of histidine and cysteine in PHSCN produces a highly
      potent derivative, Ac-PhScN-NH2 (PhScN). PhScN was 27,000- to 150,000-fold more
      potent as an inhibitor of basement membrane invasion by DU 145 and PC-3 prostate
      cancer cells. A large increase in invasion-inhibitory potency occurred after
      covalent modification of the sulfhydryl group in PHSCN to prevent disulfide bond
      formation; while the potency of covalently modified PhScN was not significantly
      increased. Thus PhScN and PHSCN invasion inhibition occurs by a noncovalent
      mechanism. These peptides also displayed similar cell surface binding
      dissociation constants (Kd), and competed for the same site. Consistent with its
      increased invasion-inhibitory potency, PhScN was also a highly potent inhibitor
      of lung extravasation and colonization in athymic nude mice: it was several
      hundred- or several thousand-fold more potent than PHSCN at blocking
      extravasation by PC-3 or DU 145 cells, and 111,000- or 379,000-fold more potent
      at inhibiting lung colonization, respectively. Furthermore, systemic 5 mg/kg
      PhScN monotherapy was sufficient to cause complete regression of established,
      intramuscular DU 145 tumors. PhScN thus represents a potent new family of
      therapeutic agents targeting metastasis by DTC's to prevent parallel progression
      in prostate cancer.

PMID- 24464035
TI  - Ceftriaxone-induced pseudolithiasis in children treated for perforated
      appendicitis.
AB  - PURPOSE: Ceftriaxone has been associated with development of pseudolithiasis. In
      our institution, it is used for treatment of perforated appendicitis in children.
      This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in
      this population. METHODS: After obtaining IRB approval, we performed a
      retrospective chart review over 51 months. We included patients undergoing
      laparoscopic appendectomy for perforated appendicitis. All patients were treated
      with ceftriaxone post-operatively. Patients without initial or post-treatment
      gallbladder imaging available for review were excluded. RESULTS: There were 71
      patients who met inclusion criteria with a mean (+/-SD) age of 10.8 +/- 3.8
      years. Of these, 14 % (n = 10) developed stones or sludge in the gallbladder. The
      mean duration of ceftriaxone therapy was 8.7 +/- 3.8 days. The average time to
      post-antibiotic imaging was 11.5 +/- 10.3 days from initiation of antibiotics.
      There was no significant difference in duration of ceftriaxone therapy in the
      children that developed pseudolithiasis or sludge (10.0 +/- 4.9 days) compared to
      those that did not (8.5 +/- 3.6, p = 0.26). One child (10 %) with pseudolithiasis
      went on to become symptomatic, requiring a laparoscopic cholecystectomy.
      CONCLUSIONS: In our experience, ceftriaxone use for perforated appendicitis is
      associated with a significant incidence of biliary pseudolithiasis, and is
      unrelated to duration of ceftriaxone therapy.

PMID- 24464036
TI  - Simulating sequential multiple assignment randomized trials to generate optimal
      personalized warfarin dosing strategies.
AB  - BACKGROUND: Due to the cost and complexity of conducting a sequential multiple
      assignment randomized trial (SMART), it is desirable to pre-define a small number
      of personalized regimes to study. PURPOSE: We proposed a simulation-based
      approach to studying personalized dosing strategies in contexts for which a
      therapeutic agent's pharmacokinetic and pharmacodynamics properties are well
      understood. We take dosing of warfarin as a case study, as its properties are
      well understood. We consider a SMART in which there are five intervention points
      in which dosing may be modified, following a loading phase of treatment. METHODS:
      Realistic SMARTs are simulated, and two methods of analysis, G-estimation and Q
      learning, are used to assess potential personalized dosing strategies. RESULTS:
      In settings where outcome modelling may be complex due to the highly non-linear
      nature of the pharmacokinetic and pharmacodynamics mechanisms of the therapeutic
      agent, G-estimation provides for which the more promising method of estimating an
      optimal dosing strategy. Used in combination with the simulated SMARTs, we were
      able to improve simulated patient outcomes and suggest which patient
      characteristics were needed to best individually tailor dosing. In particular,
      our simulations suggest that current dosing should be determined by an
      individual's current coagulation time as measured by the international normalized
      ratio (INR), their last measured INR, and their last dose. Tailoring treatment
      only based on current INR and last warfarin dose provided inferior control of INR
      over the course of the trial. LIMITATIONS: The ability of the simulated SMARTs to
      suggest optimal personalized dosing strategies relies on the pharmacokinetic and
      pharmacodynamic models used to generate the hypothetical patient profiles. This
      approach is best suited to therapeutic agents whose effects are well studied.
      CONCLUSION: Prior to investing in a complex randomized trial that involves
      sequential treatment allocations, simulations should be used where possible in
      order to guide which dosing strategies to evaluate.

PMID- 24464037
TI  - Coupling of conformational and ionization equilibria in linear
      poly(ethylenimine): a study based on the site binding/rotational isomeric state
      (SBRIS) model.
AB  - The conformational and ionization properties of linear poly(ethylenimine) are
      studied by combining the site binding model (SB) with the rotational isomeric
      state (RIS) model, developed by Flory to calculate the conformational properties
      of neutral linear molecules. The resulting approach (the SBRIS model) is used to
      rationalise the experimental poly(ethylenimine) titration curves. By fitting the
      experimental macroconstants, conformational and binding parameters are obtained.
      The obtained values are consistent with previous binding and structural
      information. The emergence of triplet interaction between protonated sites is
      explained as a natural consequence of the coupling between binding and
      conformational equilibria. When only nearest neighbour interactions are
      considered, transfer matrix techniques are used in the calculations. In order to
      account for excluded volume and long-range electrostatic interactions, Monte
      Carlo simulations are performed. The results indicate that at high ionic
      strengths, long-range interactions have a very limited impact on the titration
      curves. However, for long chains, they have a significant influence on the radius
      of gyration. 

PMID- 24464038
TI  - Rapid selection of sperm with high DNA integrity.
AB  - Sperm selection is essential to assisted reproductive technology (ART),
      influencing treatment outcomes and the health of offspring. The fundamental
      challenge of sperm selection is dictated by biology: a heterogeneous population
      of ~10(8) sperm per milliliter with a short lifetime in vitro. However,
      conventional sperm selection approaches result in less than 50% improvement in
      DNA integrity. Here, a clinically applicable microfluidic device is presented
      that selects sperm based on the progressive motility in 500 parallel
      microchannels. The result is a one-step procedure for semen purification and high
      DNA integrity sperm selection from 1 mL of raw semen in under 20 minutes.
      Experiments with bull sperm indicate more than 89% improvement in selected sperm
      vitality. Clinical tests with human sperm show more than 80% improvement in human
      DNA integrity, significantly outperforming the best current practices. These
      results demonstrate the presence of a sub-population of sperm with nearly intact
      chromatin and DNA integrity, and a simple clinically-applicable lab-on-a-chip
      method to select this population. 

PMID- 24464039
TI  - Basal ganglia subcircuits distinctively encode the parsing and concatenation of
      action sequences.
AB  - Chunking allows the brain to efficiently organize memories and actions. Although
      basal ganglia circuits have been implicated in action chunking, little is known
      about how individual elements are concatenated into a behavioral sequence at the
      neural level. Using a task in which mice learned rapid action sequences, we
      uncovered neuronal activity encoding entire sequences as single actions in basal
      ganglia circuits. In addition to neurons with activity related to the start/stop
      activity signaling sequence parsing, we found neurons displaying inhibited or
      sustained activity throughout the execution of an entire sequence. This sustained
      activity covaried with the rate of execution of individual sequence elements,
      consistent with motor concatenation. Direct and indirect pathways of basal
      ganglia were concomitantly active during sequence initiation, but behaved
      differently during sequence performance, revealing a more complex functional
      organization of these circuits than previously postulated. These results have
      important implications for understanding the functional organization of basal
      ganglia during the learning and execution of action sequences. 

PMID- 24464040
TI  - LRRK2 regulates synaptogenesis and dopamine receptor activation through
      modulation of PKA activity.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is enriched in the striatal projection
      neurons (SPNs). We found that LRRK2 negatively regulates protein kinase A (PKA)
      activity in the SPNs during synaptogenesis and in response to dopamine receptor
      Drd1 activation. LRRK2 interacted with PKA regulatory subunit IIbeta
      (PKARIIbeta). A lack of LRRK2 promoted the synaptic translocation of PKA and
      increased PKA-mediated phosphorylation of actin-disassembling enzyme cofilin and
      glutamate receptor GluR1, resulting in abnormal synaptogenesis and transmission
      in the developing SPNs. Furthermore, PKA-dependent phosphorylation of GluR1 was
      also aberrantly enhanced in the striatum of young and aged Lrrk2(-/-) mice after
      treatment with a Drd1 agonist. Notably, a Parkinson's disease-related Lrrk2
      R1441C missense mutation that impaired the interaction of LRRK2 with PKARIIbeta
      also induced excessive PKA activity in the SPNs. Our findings reveal a previously
      unknown regulatory role for LRRK2 in PKA signaling and suggest a pathogenic
      mechanism of SPN dysfunction in Parkinson's disease. 

PMID- 24464041
TI  - Tau promotes neurodegeneration through global chromatin relaxation.
AB  - The microtubule-associated protein tau is involved in a number of
      neurodegenerative disorders, including Alzheimer's disease. Previous studies have
      linked oxidative stress and subsequent DNA damage to neuronal death in
      Alzheimer's disease and related tauopathies. Given that DNA damage can
      substantially alter chromatin structure, we examined epigenetic changes in tau
      induced neurodegeneration. We found widespread loss of heterochromatin in tau
      transgenic Drosophila and mice and in human Alzheimer's disease. Notably, genetic
      rescue of tau-induced heterochromatin loss substantially reduced
      neurodegeneration in Drosophila. We identified oxidative stress and subsequent
      DNA damage as a mechanistic link between transgenic tau expression and
      heterochromatin relaxation, and found that heterochromatin loss permitted
      aberrant gene expression in tauopathies. Furthermore, large-scale analyses from
      the brains of individuals with Alzheimer's disease revealed a widespread
      transcriptional increase in genes that were heterochromatically silenced in
      controls. Our results establish heterochromatin loss as a toxic effector of tau
      induced neurodegeneration and identify chromatin structure as a potential
      therapeutic target in Alzheimer's disease. 

PMID- 24464042
TI  - Rapid and reversible knockdown of endogenous proteins by peptide-directed
      lysosomal degradation.
AB  - Rapid and reversible methods for altering the levels of endogenous proteins are
      critically important for studying biological systems and developing therapeutics.
      Here we describe a membrane-permeant targeting peptide-based method that rapidly
      and reversibly knocks down endogenous proteins through chaperone-mediated
      autophagy in vitro and in vivo. We demonstrate the specificity, efficacy and
      generalizability of the method by showing efficient knockdown of various
      proteins, including death associated protein kinase 1 (160 kDa), scaffolding
      protein PSD-95 (95 kDa) and alpha-synuclein (18 kDa), with their respective
      targeting peptides in a dose-, time- and lysosomal activity-dependent manner in
      rat neuronal cultures. Moreover, we show that, when given systemically, the
      peptide system efficiently knocked down the targeted protein in the brains of
      intact rats. Our study provides a robust and convenient research tool for
      manipulating endogenous protein levels and may also lead to the development of
      protein knockdown-based therapeutics for treating human diseases. 

PMID- 24464043
TI  - Oxytocin mediates early experience-dependent cross-modal plasticity in the
      sensory cortices.
AB  - Sensory experience is critical to development and plasticity of neural circuits.
      Here we report a new form of plasticity in neonatal mice, where early sensory
      experience cross-modally regulates development of all sensory cortices via
      oxytocin signaling. Unimodal sensory deprivation from birth through whisker
      deprivation or dark rearing reduced excitatory synaptic transmission in the
      correspondent sensory cortex and cross-modally in other sensory cortices. Sensory
      experience regulated synthesis and secretion of the neuropeptide oxytocin as well
      as its level in the cortex. Both in vivo oxytocin injection and increased sensory
      experience elevated excitatory synaptic transmission in multiple sensory cortices
      and significantly rescued the effects of sensory deprivation. Together, these
      results identify a new function for oxytocin in promoting cross-modal, experience
      dependent cortical development. This link between sensory experience and oxytocin
      is particularly relevant to autism, where hypersensitivity or hyposensitivity to
      sensory inputs is prevalent and oxytocin is a hotly debated potential therapy. 

PMID- 24464044
TI  - Resolving human object recognition in space and time.
AB  - A comprehensive picture of object processing in the human brain requires
      combining both spatial and temporal information about brain activity. Here we
      acquired human magnetoencephalography (MEG) and functional magnetic resonance
      imaging (fMRI) responses to 92 object images. Multivariate pattern classification
      applied to MEG revealed the time course of object processing: whereas individual
      images were discriminated by visual representations early, ordinate and
      superordinate category levels emerged relatively late. Using representational
      similarity analysis, we combined human fMRI and MEG to show content-specific
      correspondence between early MEG responses and primary visual cortex (V1), and
      later MEG responses and inferior temporal (IT) cortex. We identified transient
      and persistent neural activities during object processing with sources in V1 and
      IT. Finally, we correlated human MEG signals to single-unit responses in monkey
      IT. Together, our findings provide an integrated space- and time-resolved view of
      human object categorization during the first few hundred milliseconds of vision. 

PMID- 24464045
TI  - Special section guest editorial: advanced biomedical imaging and sensing.

PMID- 24464046
TI  - Electric field Monte Carlo simulation of focused stimulated emission depletion
      beam, radially and azimuthally polarized beams for in vivo deep bioimaging.
AB  - An electric field Monte Carlo method is used to study the focal spot of a
      stimulated emission depletion (STED) beam, radially and azimuthally polarized
      beams in a turbid medium as a function of the scattering coefficient. To consider
      the diffraction of light of the wave nature, the wavefront is decomposed into a
      set of secondary spherical subwaves according to the Huygens principle. From the
      simulation results, we can find that the STED beam can still form a doughnut
      focal spot inside the turbid medium. These simulation results are important for
      the feasibility study of STED microscopy for in vivo deep bioimaging. Similarly,
      the focal spot for an azimuthally polarized beam can also keep a doughnut spot at
      the focal plane in a turbid medium.

PMID- 24464047
TI  - Infectious disease research investments follow colonial ties: questionable
      ethics.
AB  - BACKGROUND: International funding for global health research is not
      systematically documented. We have assessed the level of research funding awarded
      by UK funders of international research to low- and middle-income countries or
      research institutions in these countries. METHODS: We analysed 6165 studies; from
      these we selected 522 that matched our criteria and used them to evaluate
      research funding by pathogen, disease, research and development value chain,
      funding organisation and country. RESULTS: Investment in infectious disease
      research in the countries studied totalled L264 million. Distribution of research
      investments closely mirrored that of the UK's former colonial territories; the
      top five countries, and eight of the top 10, have historical links with the UK,
      being current or former members of the Commonwealth of Nations. HIV, malaria and
      neglected tropical diseases attracted the greatest investment (L219 million;
      82.8%), with most studies focussing on operational and epidemiological research
      (L109 million; 41.3%). CONCLUSIONS: International financing of infectious disease
      research by UK funding organisations follows former colonial ties. Funding
      institutions should review their funding policies to ensure that they also assist
      low- and middle-income countries without colonial ties to address their disease
      burden. A global investment surveillance system is needed to map and monitor
      funding for international research and guide the allocation of scarce resources
      to reduce the global disease burden.

PMID- 24464048
TI  - OSU-CG5, a novel energy restriction mimetic agent, targets human colorectal
      cancer cells in vitro.
AB  - AIM: Energy-restriction mimetic agents (ERMAs) are small-molecule agents that
      target various aspects of energy metabolism, which has emerged as a promising
      approach in cancer therapy. In the current study, we tested the ability of OSU
      CG5, a novel ERMA, to target human colorectal cancer (CRC) in vitro. METHODS: Two
      human CRC cell lines (HCT-116 and Caco-2) were tested. Cell viability was
      assessed using MTT assay. Caspase-3/7 activities were measured using Caspase-Glo
      3/7 assay kit. Western blot analysis was used to measure the expression of
      relevant proteins in the cells. Glucose consumption of the cells was detected
      using glucose uptake cell-based assay kit. RESULTS: OSU-CG5 dose-dependently
      inhibited HCT-116 and Caco-2 cell proliferation with the IC50 values of 3.9 and
      4.6 MUmol/L, respectively, which were 20-25-fold lower than those of resveratrol,
      a reference ERMA. Both OSU-CG5 (5, 10, and 20 MUmol/L) and resveratrol (50, 100,
      and 200 MUmol/L) dose-dependently increased caspase-3/7 activity and PARP level
      in the cells. Furthermore, both OSU-CG5 and resveratrol induced dose-dependent
      energy restriction in the cells: they suppressed glucose uptake and Akt
      phosphorylation, decreased the levels of p-mTOR and p-p70S6K, increased the
      levels of ER stress response proteins GRP78 and GADD153, and increased the level
      of beta-TrCP, which led to the downregulation of cyclin D1 and Sp1. CONCLUSION:
      OSU-CG5 exhibits promising anti-cancer activity against human CRC cells in vitro,
      which was, at least in part, due to energy restriction and the consequent
      induction of ER stress and apoptosis.

PMID- 24464049
TI  - Recent progress regarding the bioactivities, biosynthesis and synthesis of
      naturally occurring resorcinolic macrolides.
AB  - Macrolides, which comprise a family of lactones with different ring sizes, belong
      to the polyketide class of natural products. Resorcinolic macrolides, an
      important subgroup, possess interesting structures and exhibit a wide variety of
      bioactivities, such as anti-tumor, anti-bacteria, and anti-malaria activities,
      etc. This review summarizes progress in isolation, bioactivity studies,
      biosynthesis, and representative chemical syntheses of this group of macrolides
      in recent decades, encompassing 63 naturally occurring macrolides published in
      120 articles. 

PMID- 24464050
TI  - Neuronal nicotinic acetylcholine receptors are important targets for alcohol
      reward and dependence.
AB  - Neuronal nicotinic acetylcholine receptors are important targets for alcohol
      reward and dependence. Alcoholism is a serious public health problem and has been
      identified as the third major cause of preventable mortality in the world.
      Worldwide, about 2 billion people consume alcohol, with 76.3 million having
      diagnosable alcohol use disorders. Alcohol is currently responsible for the death
      of 4% of adults worldwide (about 2.5 million deaths each year), and this number
      will be significantly increased by 2020 unless effective action is taken. Alcohol
      is the most commonly abused substance by humans. Ethanol (EtOH) is the
      intoxicating agent in alcoholic drinks that can lead to abuse and dependence.
      Although it has been extensively studied, the mechanisms of alcohol reward and
      dependence are still poorly understood. The major reason is that, unlike other
      addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular
      targets, EtOH affects much wider neuronal functions. These functions include
      phospholipid membranes, various ion channels and receptors, synaptic and network
      functions, and intracellular signaling molecules. The major targets in the brain
      that mediate EtOH's effects remain unclear. This knowledge gap results in a
      therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and
      nicotine are often co-abused, which suggests that neuronal nicotinic
      acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also
      contribute to alcohol's abusive properties. Here, we briefly summarize recent
      lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway,
      which provides a perspective that nAChRs are important targets mediating alcohol
      abuse. 

PMID- 24464052
TI  - Patient safety and pain in IV therapy.

PMID- 24464051
TI  - Downregulation of sFRP-2 by epigenetic silencing activates the beta-catenin/Wnt
      signaling pathway in esophageal basaloid squamous cell carcinoma.
AB  - Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare variant of
      typical squamous cell carcinoma (SCC) associated with poor survival. A
      characteristic feature is nuclear accumulation of beta-catenin, without a
      mutation of the gene. We studied the methylation status of Wnt antagonist genes,
      such as secreted frizzled-related protein (sFRP) gene family members, Wnt
      inhibitory factor-1 (WIF-1), Dickkopf-1 (Dkk-1), and human Dapper protein-1 (HDPR
      1), and alterations of the APC, Axin1, and Axin2 genes in 30 cases of esophageal
      BSCC. beta-catenin and sFRP (sFRP-1, sFRP-2, sFRP-4, sFRP-5) protein expression
      was examined by immunohistochemistry. APC, Axin1, and Axin2 gene mutations were
      detected in 3, 2, and 2 cases, respectively, and 6 cases (20 %) harbored at least
      1 alteration in these genes. Methylation of the sFRP-2 promoter region was
      observed in all cases, and methylation was frequent in sFRP-1 and sFRP-5, but
      infrequent in Dkk-1, WIF-1, sFRP-4, and HDPR-1. sFRP-2 expression was almost
      completely absent in 25 cases (83 %), consistent with the methylation status.
      Nuclear accumulation of beta-catenin was observed in all cases. sFRP-5 expression
      was associated with a low nuclear beta-catenin labeling index. These results show
      that sFRP-2 is a target gene of hypermethylation in esophageal BSCC and suggest
      that sFRP-2 might contribute to BSCC tumorigenesis through the Wnt/beta-catenin
      signaling pathway. 

PMID- 24464053
TI  - Reducing PICC migrations and improving patient outcomes.
AB  - Inadvertent migration of central venous catheters can lead to several issues
      including delayed therapy and clinical morbidities such as thrombosis.
      Peripherally inserted central catheters (PICCs) are particularly at risk of
      movement. An innovative new device which allows anchorage of the catheter has
      proved very successful in the minimisation of catheter migration. The SecurAcath
      device incorporates a small blunt anchor which lies beneath the skin in order to
      secure the catheter in place and prevent inadvertent movement. An evaluation of
      31 patients with a SecurAcath device in situ to secure a PICC found only one case
      of insignificant catheter migration. Some initial problems with infection and
      pain were encountered and interventions were put in place to minimise their
      incidence. SecurAcath removal proved to be the most significant challenge but
      this can be overcome with suitable guidance and training.

PMID- 24464054
TI  - Intravenous versus subcutaneous access for palliative care patients.
AB  - The subcutaneous route for medication administration can prove highly effective
      both in terms of reliability and clinical outcomes. It is also well tolerated by
      patients for whom the enteral route is not an option. This extended feature
      comment reviews the advantages and disadvantages of both the intravenous and
      subcutaneous routes of medication administration for patients requiring
      palliation. 

PMID- 24464055
TI  - Getting the most from ultrasound guidance for CVC insertion.
AB  - Ultrasound is an imaging technique that uses ultra-high frequency sound waves.
      The interaction of the sound waves with body tissue enables an image to be
      produced. Following guidance from the National Institute for Health and Care
      Excellence (NICE) (2002), the use of two-dimensional ultrasound imaging for
      central venous catheter (CVC) insertion has increased. Ultrasound provides the
      nurse with visualisation of the target vein as well as any other surrounding
      structures. It also demonstrates any variation in anatomy that the patient may
      have. Increased first-time puncture rates and decreased complications are among
      the benefits of ultrasound use for CVC placement described in the literature.
      However, NICE (2002) guidance recommended that education and training be sought
      by those using this technology. The aim of this article, therefore, is to provide
      useful information regarding ultrasound-guided venous access and to describe some
      techniques to improve image quality. 

PMID- 24464056
TI  - Competence is central to vascular access care.

PMID- 24464057
TI  - Sharps legislation and assessment of needle protection systems.
AB  - Needlestick injuries (NSIs) carry the potential for transmission of serious blood
      borne infections and pose a significant risk to patients and healthcare staff.
      These infections come with an estimated cost of L300 million per year in the UK
      (Saia et al, 2010). An EU directive mandated in May of 2013 has sought to
      minimise the risk of NSI though the introduction of needle-protection systems.
      The authors of this article set out to assess nursing knowledge of this
      legislation and ascertain which needle-protection systems for low-molecular
      weight heparin/anti Xa (for subcutaneous administration) were preferred in a
      large teaching trust. Approximately half of the nurses questioned had some
      knowledge of the legislation and almost all agreed that there is a need for
      needle protection systems. All four devices tested meet requirements for the
      legislation but the preferred devices were the needle protection system for
      enoxaparin and fondaparinux with a self-sheathing style device after activation. 

PMID- 24464058
TI  - [How should" education" be in Japanese Society of Radiological Technology?
      (discussion)].

PMID- 24464059
TI  - [Decision process of Notification Value by the Dose Index Registry system in X
      ray computed tomography].
AB  - A new technical standard for X-ray computed tomography (CT) has been published by
      the National Electrical Manufacturers Association (NEMA) that allows the Alert
      Value and Notification Value for cumulative dose to be configurable by CT systems
      operators in conjunction with the XR-25 (Dose check) standard. In this study, a
      decision method of the Notification Values for reducing the radiation dose was
      examined using the dose index registry (DIR) system, during 122 continuous days
      from August 1, 2012 to November 30, 2012. CT images were obtained using the
      Discovery CT 750HD (GE Healthcare) and the dose index was calculated using the
      DoseWatch DIR system. The CT dose index-volume (CTDIvol) and dose-length product
      (DLP) were output from the DIR system in comma-separated value (CSV) file format
      for each examination protocol. All data were shown as a schematic boxplot using
      statistical processing software. The CTDIvol of a routine chest examination
      showed the following values (maximum: 23.84 mGy; minimum: 2.55 mGy; median: 7.60
      mGy; 75% tile: 10.01 mGy; 25% tile: 6.54 mGy). DLP showed the following values
      (maximum: 944.56 mGy.cm; minimum: 97.25 mGy.cm; median: 307.35 mGy.cm; 75% tile:
      406.87 mGy.cm; 25% tile: 255.75 mGy.cm). These results indicate that the 75% tile
      of CTDIvol and DLP as an initial value proved to be safe and efficient for CT
      examination and operation. We have thus established one way of determining the
      Notification Value from the output of the DIR system. Transfer back to the
      protocol of the CT and automated processing each numeric value in the DIR system
      is desired. 

PMID- 24464060
TI  - [Development of a batched image delete system for multi-vender picture archiving
      and communication system environment].
AB  - A picture archiving and communication system (PACS) for multi-vendor imaging
      servers is useful, since it can provide a variety of image-processing services.
      However, to delete an image file in the PACS, it is necessary to delete not only
      the image but all its associated images that are stored in multiple servers: this
      is a lengthy and painstaking process. To reduce this workload, we have developed
      a system consisting of a computer program with a graphical user interface that
      can delete the target image and all related images by means of batch processing.
      The developed system creates an extensible markup language (XML)-format file that
      describes the operation for deleting an image and forwards the XML file to the
      main server. Using a Windows file-sharing system (SMB/CIFS), each server shares
      the XML file and deletes the images in its own database in response to the
      instructions described in the XML file. We can also rigorously manage information
      concerning the deleted images using the information that is output from the main
      server to external storage. We also discuss the degree of load reduction in our
      system compared with that of ordinary systems. 

PMID- 24464061
TI  - [Development of cloud chamber having thin-film entrance windows and proposal of
      practical training for beginners using X-ray equipment and unsealed radioactive
      material].
AB  - A cloud chamber is a detector that can visualize the tracks of charged particles.
      Hayashi, et al. suggested a visualization experiment in which X-rays generated by
      diagnostic X-ray equipment were directed into a cloud chamber; however, there was
      a problem in that the wall of the cloud chamber scattered the incoming X-rays. In
      this study, we developed a new cloud chamber with entrance windows. Because these
      windows are made of thin film, we were able to direct the X-rays through them
      without contamination by scattered X-rays from the cloud chamber wall. We have
      newly proposed an experiment in which beta-particles emitted from radioisotopes
      are directed into a cloud chamber. We place shielding material in the cloud
      chamber and visualize the various shielding effects seen with the material
      positioned in different ways. During the experiment, electrons scattered in the
      air were measured quantitatively using GM counters. We explained the physical
      phenomena in the cloud chamber using Monte Carlo simulation code EGS5. Because
      electrons follow a tortuous path in air, the shielding material must be placed
      appropriately to be able to effectively block their emissions. Visualization of
      the tracks of charged particles in this experiment proved effective for
      instructing not only trainee radiological technologists but also different types
      of healthcare professionals. 

PMID- 24464062
TI  - [Development of a quality assurance phantom for brachytherapy: the feasibility of
      daily check with the phantom].
AB  - PURPOSE: We developed a quality assurance (QA) phantom to enable easy
      confirmation of radiation source output measurements of a high dose rate (192)Ir
      intracavitary brachytherapy unit in gynecology. The purpose of this study was to
      evaluate the feasibility of daily checks using the QA phantom. METHODS AND
      MATERIALS: The QA phantom was designed with tough water phantoms to hold a Farmer
      type ionization chamber, with semiconductor detectors used as in vivo dosimeters
      to measure rectal dose, and three transfer tubes for gynecology. To test the
      reliability of our QA phantom for the detection of abnormalities in source output
      or semiconductor detectors, we applied different doses. RESULTS: Variations due
      to different settings of the QA phantom were within 2%. The temporal variations
      were less than 2% and 5% in the Farmer-type ionization chamber and semiconductor
      detectors, respectively. Interobserver variations were below 3%. CONCLUSIONS:
      With tolerance levels of 2% and 5% for a Farmer-type ionization chamber and
      semiconductor detectors, respectively, a QA phantom is potentially useful for
      easily detecting abnormalities by applying daily checks of the brachytherapy
      unit.

PMID- 24464063
TI  - [Computed tomography colonography image assessment using colon phantom-effects of
      reconstructed slice thickness].
AB  - Computed tomography colonography (CTC) is a robust and reliable imaging test of
      the colon. Recent studies show good sensitivity for the identification of
      nonpolypoid (flat) lesions as well. The purpose of this study was to determine
      the accuracy and reproducibility of a volume-rendering (VR) and virtual gross
      pathology (VGP) technique for detecting a polypoid lesion phantom by varying
      slice thickness. The scan of a simulated house-made phantom was performed using a
      16-slice CT scanner with varying combinations of tube voltage (120 kVp),
      effective exposure (100 mAs), detector configuration (16*0.75 mm), rotation time
      (0.75 s), helical pitch (0.688, 0.938, 1.066 and 1.188), reconstruction kernel
      (A, B and C), and section thickness/reconstruction interval (0.8/0.4, 1.0/0.5 and
      1.5/0.75 mm). All image data were transferred to a three-dimensional workstation
      to assess multi-planar reformation (MPR), VR and VGP. Accuracy of volume
      measurement using the VR technique for quantitative analysis was compared using a
      paired t-test. Four radiological technologists also independently evaluated the
      visual score using the VGP technique for qualitative analysis, and their
      evaluations were compared using one-way analysis of variance with Fisher's
      protected least significant difference post-hoc test. There was a statistically
      significant difference in reproducibility between the three different slice
      thicknesses as to volume measurement and observer performance test (p<0.01 and
      p<0.05, respectively). Furthermore, the reproducibility improved when using
      thinner slices. In conclusion, VR and VGP techniques using a slice thickness of
      0.8 mm made it possible to maintain accuracy and reproducibility when using CTC
      to detect polypoid lesions. 

PMID- 24464064
TI  - [Availability of using diaphragm matching in stereotactic body radiotherapy
      (SBRT) at the time in breath-holding SBRT for liver cancer].
AB  - PURPOSE: Liver image guided radiation therapy (IGRT) based on bone matching risks
      generating serious target positioning errors for reasons of lack of
      reproducibility of expiration breath hold. We therefore investigated the
      feasibility of 3D image matching between planning CT images and pretreatment cone
      beam computed tomography (CBCT) images based on diaphragm surface matching.
      METHOD: 27 liver stereotactic body radiotherapy (SBRT) cases in whom
      trancecatheter arterial chemoembolization (TACE) had been performed in advance of
      radiotherapy were manually image-matched based on contrast, Lipiodol used in the
      TACE as the marker of the tumor, and the relative coordinates of the isocenter
      obtained by contrast matching, defined as the reference coordinate. The target
      positioning difference between diaphragm matching and bone matching were
      evaluated by using relative coordinates of the isocenter from the reference
      obtained for each matching technique. RESULTS: The target positioning error using
      diaphragm matching and bone matching was 1.31+/-0.83 and 3.10+/-2.80 mm in the
      cranial-caudal (C-C) direction, 1.04+/-0.95 and 1.62+/-1.02 mm in the anterior
      posterior (A-P) direction, and 0.93+/-1.19 and 1.12+/-0.94 mm in the left-right
      (L-R) direction, respectively. The positioning error due to diaphragm matching
      was significantly smaller than for bone matching in the C-C direction (p<0.05).
      CONCLUSION: IGRT based on diaphragm matching has potential as an alternative
      image matching technique for the positioning of liver patients.

PMID- 24464065
TI  - [Preventive measures against human error based on the classification of the
      adverse events].
AB  - It is impossible to entirely eliminate human error; however, systematic attempts
      have been made to comprehensively minimize accidents originating in human error.
      It appears that the "work classification" we proposed previously is not able to
      reduce adverse events, fifty percent of which were duty confirmation failures. We
      have therefore reviewed and classified the causes of human error from the
      perspective of working conditions to create a simpler and more preventative
      strategy. Text-mining analysis was applied to speech part classification to
      reveal areas with room for improvement. In an objective approach, a conduct code
      was created and put into practice, based on the common features revealed from a
      classification of human error in the examples investigated. The average number of
      accidents per year was reduced from 36 to 24, and those due to human error per
      year were reduced from 17.6 to 11. This objective approach appears to achieve a
      reduction of adverse events, including those caused by human error. However,
      these results were obtained over only one year, in a single-center analysis, and
      thus, widespread and continuous enforcement would be needed to demonstrate the
      validity of this objective approach to the prevention of human error. 

PMID- 24464066
TI  - [Evaluation study of abnormal detectability with Thurstone and Scheffe (Nakaya)
      of paired comparison method using chest phantom].
AB  - Monitors are increasingly being used as diagnostic imaging devices. In this
      study, using an all-purpose liquid-crystal display (LCD), the rate of detection
      of abnormalities was investigated using Thurstone's and Scheffe's (Nakaya) paired
      comparison methods. A chest phantom was prepared as a test sample with acryl and
      aluminum plates and intensities suggesting small adenocarcinomas. For the
      acquisition conditions for computed radiography, after setting the baseline at a
      dose at which the film density of the standard screen-film system at the same as
      those for the lung, costal bone, and mediastinum, 5 steps of 2-fold serial doses
      were then set: 1/4, 1/2, 1, 2, and 4. The test sample was observed by 10
      students. On the Thurstone scale, detectability decreased with a decrease in the
      dose in the lung, costal bone, and mediastinum. When the significance of
      differences between the values at adjacent doses was investigated using the
      yardstick method, using Scheffe's method revealed a significant difference
      between the 4- and 2-fold doses and between the 1/2 and 1/4 doses in the
      pulmonary region. A significant difference was also noted between the baseline
      and 1/2 doses in the mediastinum. Changes in the order of the scale values may
      not occur in the intervals in which significant differences were noted using
      Scheffe's methods. 

PMID- 24464067
TI  - [Symposium 1: the future of the molecular imaging in Japan].

PMID- 24464068
TI  - [Needs of research for technologist-assisted diagnosis (TAD)].

PMID- 24464069
TI  - [Changes in radiological technology research for medical imaging: from analogue
      to digital image studies].

PMID- 24464072
TI  - [Report on the 21st Chinese Society of Imaging Technology].

PMID- 24464070
TI  - [7. Nuclear cardiology in ischemic heart disease].

PMID- 24464073
TI  - [World Trend of Medical Radiation Control].

PMID- 24464074
TI  - [Our growth beyond the globalization and transdisciplinary].

PMID- 24464075
TI  - Uptake and accumulation of antimicrobials, triclocarban and triclosan, by food
      crops in a hydroponic system.
AB  - Commonly used in personal care products, triclocarban (TCC) and triclosan (TCS)
      are two chemicals with antimicrobial properties that have recently been
      recognized as environmental contaminants with the potential to adversely affect
      human health. The objective of the study described herein was to evaluate the
      potential of food crops to uptake TCC and TCS. Eleven food crops, grown in
      hydroponic nutrient media, were exposed to a mixture of 500 MUg L(-1) TCC and
      TCS. After 4 weeks of exposure, roots accumulated 86-1,350 mg kg(-1) of
      antimicrobials and shoots had accumulated 0.33-5.35 mg kg(-1) of antimicrobials.
      Translocation from roots to shoots was less than 1.9 % for TCC and 3.7 % for TCS,
      with the greatest translocation for TCC observed for pepper, celery, and
      asparagus and for TCS observed for cabbage, broccoli, and asparagus. For edible
      tuber- or bulb-producing crops, the concentrations of both TCC and TCS were lower
      in the tubers than in the roots. Exposure calculations using national consumption
      data indicated that the average exposure to TCC and TCS from eating contaminated
      crops was substantially less than the exposure expected to cause adverse effects,
      but exceeded the predicted exposure from drinking water. Exposure to
      antimicrobials through food crops would be substantially reduced through limiting
      consumption of beets and onions. 

PMID- 24464076
TI  - Coagulation settling characteristics and eliminating pollution analysis of fine
      grind natural zeolite in static and turbulent flow.
AB  - The phenomenon of coagulation settling in liquid suspensions has a variety of
      applications, including mineral processing, treatment of industrial effluents,
      and municipal sewage sludge purification. This study was to investigate the
      coagulation settling characteristics of fine-grind natural zeolite and evaluate
      the removal efficiency of contaminants simultaneously in static and turbulent
      flow. A series of column experiments were conducted to pattern the
      characteristics of spatial and temporal variation of coagulation settling and
      removal contaminants in static and turbulent flow. The results indicated that the
      suspended solid concentration presented an apparent exponential decay with
      coagulation settling time in static flow (R (2)  > 0.99), coagulation settling
      rate of the fine zeolite-suspended solid in static flow was between 0.005 and
      0.05 cm/s obtained from the repeat depth suction method. The relation between
      average C/C 0 of pollutants and suspended solid concentration was exponential
      before the settlement for 24 h and that was the line after the settlement for 24
      h. Several various models were presented to highlight the coagulation settling
      characteristics of fine-grind natural zeolite in static and turbulent flow.
      Compared to hydrostatic settling experiments, zeolite-suspended solid presented
      better removal efficiency of pollutants and greater removal rate of pollutants in
      turbulent flow. 

PMID- 24464077
TI  - Investigating hydrochemistry of groundwater in Indo-Gangetic alluvial plain using
      multivariate chemometric approaches.
AB  - Groundwater hydrochemistry of an urban industrial region in Indo-Gangetic plains
      of north India was investigated. Groundwater samples were collected both from the
      industrial and non-industrial areas of Kanpur. The hydrochemical data were
      analyzed using various water quality indices and nonparametric statistical
      methods. Principal components analysis (PCA) was performed to identify the
      factors responsible for groundwater contamination. Ensemble learning-based
      decision treeboost (DTB) models were constructed to develop discriminating and
      regression functions to differentiate the groundwater hydrochemistry of the three
      different areas, to identify the responsible factors, and to predict the
      groundwater quality using selected measured variables. The results indicated non
      normal distribution and wide variability of water quality variables in all the
      study areas, suggesting for nonhomogenous distribution of sources in the region.
      PCA results showed contaminants of industrial origin dominating in the region.
      DBT classification model identified pH, redox potential, total-Cr, and lambda 254
      as the discriminating variables in water quality of the three areas with the
      average accuracy of 99.51 % in complete data. The regression model predicted the
      groundwater chemical oxygen demand values exhibiting high correlation with
      measured values (0.962 in training; 0.918 in test) and the respective low root
      mean-squared error of 2.24 and 2.01 in training and test arrays. The statistical
      and chemometric approaches used here suggest that groundwater hydrochemistry
      differs in the three areas and is dominated by different variables. The proposed
      methods can be used as effective tools in groundwater management. 

PMID- 24464078
TI  - Variations in source apportionments of nutrient load among seasons and
      hydrological years in a semi-arid watershed: GWLF model results.
AB  - Quantifying source apportionments of nutrient load and their variations among
      seasons and hydrological years can provide useful information for watershed
      nutrient load reduction programs. There are large seasonal and inter-annual
      variations in nutrient loads and their sources in semi-arid watersheds that have
      a monsoon climate. The Generalized Watershed Loading Function model was used to
      simulate monthly nutrient loads from 2004 to 2011 in the Liu River watershed,
      Northern China. Model results were used to investigate nutrient load
      contributions from different sources, temporal variations of source
      apportionments and the differences in the behavior of total nitrogen (TN) and
      total phosphorus (TP). Examination of source apportionments for different seasons
      showed that point sources were the main source of TN and TP in the non-flood
      season, whereas contributions from diffuse sources, such as rural runoff, soil
      erosion, and urban areas, were much higher in the flood season. Furthermore,
      results for three typical hydrological years showed that the contribution ratios
      of nutrient loads from point sources increased as streamflow decreased, while
      contribution ratios from rural runoff and urban area increased as streamflow
      increased. Further, there were significant differences between TN and TP sources
      on different time scales. Our findings suggest that priority actions and
      management measures should be changed for different time periods and hydrological
      conditions, and that different strategies should be used to reduce loads of
      nitrogen and phosphorus effectively. 

PMID- 24464079
TI  - Medium optimization for the production of anti-cyanobacterial substances by
      Streptomyces sp. HJC-D1 using response surface methodology.
AB  - Bioremediation using isolated anti-cyanobacterial microorganism has been widely
      applied in harmful algal blooms (HABs) control. In order to improve the secretion
      of activated anti-cyanobacterial substances, and lower the cost, a sequential
      optimization of the culture medium based on statistical design was employed for
      enhancing the anti-cyanobacterial substances production and chlorophyll a (Chl a)
      removal by Streptomyces sp. HJC-D1 in the paper. Sucrose and KNO3 were selected
      as the most suitable carbon and nitrogen sources based on the one-at-a-time
      strategy method, and sucrose, KNO3 and initial pH were found as major factors
      that affected the anti-cyanobacterial ability of the isolated stain via the
      Plackett-Burman design. Based on the response surface and canonical analysis, the
      optimum condition of culture medium was obtained at 22.73 g l(-1) of sucrose,
      0.96 g l(-1) of KNO3, and initial pH 8.82, and the Chl a removal efficiency by
      strain HJC-D1 increased from 63 +/- 2 % to 78 +/- 2 % on the optimum conditions. 

PMID- 24464080
TI  - Isolation and characterization of formaldehyde-degrading fungi and its
      formaldehyde metabolism.
AB  - Formaldehyde is classified as a human carcinogen that may cause nasopharyngeal
      cancer and probably leukemia. The effects of environmental and nutritional
      factors on fungal growth and the biodegradation of formaldehyde were
      investigated. Fungal strains SGFA1 and SGFA3 isolated from untreated sewage
      sediment samples collected from heavily formaldehyde-contaminated areas were
      identified using morphological characteristics and molecular techniques and named
      as Aspergillus nomius SGFA1 and Penicillium chrysogenum SGFA3. Results indicate
      that SGFA1 and SGFA3 completely consumed 3,000 and 900 mg l(-1) of formaldehyde,
      respectively, within 7 days under optimized conditions. Quantitative real-time
      PCR analyses and enzyme activity analyses demonstrated that glutathione-dependent
      formaldehyde dehydrogenase (GDFADH) and formate dehydrogenase (FDH) pathway may
      play a functional role in enhancing formaldehyde-degrading capability in SGFA1.
      Both fungi have potential use for remediation of formaldehyde pollution. 

PMID- 24464082
TI  - Behavior of particulate matter during high concentration episodes in Seoul.
AB  - The behavior of particulate matter (PM) during high-concentration episodes was
      investigated using monitoring data from Guui station, a comprehensive air
      monitoring station in Seoul, Korea, from January 2008 to March 2010. Five non
      Asian dust (ND) episodes and two Asian dust (AD) episodes of high PM
      concentrations were selected for the study. During the ND episode, primary air
      pollutants accumulated due to low wind speeds, and PM2.5 increased along with
      most other air pollutants. Particles larger than PM2.5 were also high since these
      particles were generated by vehicular traffic rather than wind erosion. During
      strong AD episodes, PM10-2.5 primarily increased and gaseous primary air
      pollutants decreased under high wind speeds. However, even during the AD episode,
      PM2.5 and gaseous primary air pollutants increased when the effects of AD were
      weak and wind speeds were low. This study corroborates that accumulation of air
      pollutants due to a drop in surface wind speed plays an important role in short
      term high-concentration occurrences. However, low wind speeds could not be
      directly linked to local emissions because a significant portion of accumulated
      air pollutants resulted from long-range transport. 

PMID- 24464081
TI  - Temperature influence on biological phosphorus removal induced by
      aerobic/extended-idle regime.
AB  - Previous researches have demonstrated that biological phosphorus removal (BPR)
      from wastewater could be driven by the aerobic/extended-idle (A/EI) regime. This
      study further investigated temperature effects on phosphorus removal performance
      in six A/EI sequencing batch reactors (SBRs) operated at temperatures ranging
      from 5 to 30  degrees C. The results showed that phosphorus removal efficiency
      increased with temperature increasing from 5 to 20  degrees C but slightly
      decreased when temperature continually increased to 30  degrees C. The highest
      phosphorus removal rate of 97.1 % was obtained at 20  degrees C. The biomass
      cultured at 20  degrees C contained more polyphosphate accumulating organisms
      (PAO) and less glycogen accumulating organisms (GAO) than that cultured at any
      other temperatures investigated. The mechanism studies revealed that temperature
      affected the transformations of glycogen and polyhydroxyalkanoates, and the
      activities of exopolyphosphatase and polyphosphate kinase activities. In
      addition, phosphorus removal performances of the A/EI and traditional
      anaerobic/oxic (A/O) SBRs were compared at 5 and 20  degrees C, respectively. The
      results showed the A/EI regime drove better phosphorus removal than the A/O
      regime at both 5 and 20  degrees C, and more PAO and less GAO abundances in the
      biomass might be the principal reason for the higher BPR in the A/EI SBRs as
      compared with the A/O SBRs. 

PMID- 24464083
TI  - Named consultant for hospital patients will end culture of "brief encounters,"
      says England's health secretary.

PMID- 24464084
TI  - Crutch art painting in the Middle Ages as orthopaedic heritage (part II: the peg
      leg, the bent-knee peg and the beggar).
AB  - Little of historical value about crutches can be ascertained before the Middle
      Ages. In contrast, the Middle Ages offer many examples for the study of crutches.
      Even if no medical report can be found, the immense patronage of the Church,
      encouraging artists to portray the saints and their miracles, has left great
      masterpieces that drew people with crutches. Pictures and the history of medieval
      conceptions of disability appear to provide an interesting chronicle of surgery
      of the peg leg and the bent-knee peg among the representations of cripples and
      beggars. 

PMID- 24464085
TI  - Psychopathy, neurotechnologies, and neuroethics.

PMID- 24464086
TI  - Sensitivity to external signals and synchronization properties of a non
      isochronous auto-oscillator with delayed feedback.
AB  - For auto-oscillators of different nature (e.g. active cells in a human heart
      under the action of a pacemaker, neurons in brain, spin-torque nano-oscillators,
      micro and nano-mechanical oscillators, or generating Josephson junctions) a
      critically important property is their ability to synchronize with each other.
      The synchronization properties of an auto oscillator are directly related to its
      sensitivity to external signals. Here we demonstrate that a non-isochronous
      (having generation frequency dependent on the amplitude) auto-oscillator with
      delayed feedback can have an extremely high sensitivity to external signals and
      unusually large width of the phase-locking band near the boundary of the stable
      auto-oscillation regime. This property could be used for the development of
      synchronized arrays of non-isochronous auto-oscillators in physics and
      engineering, and, for instance, might bring a better fundamental understanding of
      ways to control a heart arrythmia in medicine. 

PMID- 24464087
TI  - Families United/Familias Unidas: family group office visits to reduce risk
      factors for type 2 diabetes.
AB  - PURPOSE: The purpose of the Families United/Familias Unidas study was to evaluate
      the feasibility and efficacy of group office visits on reducing diabetes risk in
      a multiethnic, primary care population. METHODS: Adults, ages 18 to 70 years,
      with any diabetes risk factor were recruited to attend 12 group office visits
      over 6 months. Each participant identified 1 support person, age 14 to 70 years,
      to accompany them. Data were collected at baseline, postintervention, 6 months,
      and 12 months. Primary outcome measures were reduction in the total number of
      predefined, modifiable risk factors (ie, body mass index >=25 kg/m(2); waist
      circumference >=88 cm [women], >=102 cm [men]; blood pressure >=140/90 mm Hg;
      hemoglobin A1C >=5.7%; fasting insulin >=15 uU/mL; glycemic index >=52.5%
      [women], >=53.4% [men]; and physical activity <150 min/wk). RESULTS: Thirty-nine
      participants/supporters completed the intervention (mean age 47.8 +/- 12.3 years,
      69.2% female, 61.5% white, 35.9% Latino). Risk reduction analysis included only
      participants/supporters who remained paired at the intervention's end (n = 36).
      At baseline, primary participants (n = 18) had an average of 4.8 +/- 1.6
      (standard error) predefined risk factors; supporters (n = 18), 4.1 +/- 1.4.
      Primary participants' risk factors decreased approximately 15% immediately after
      the 6-month intervention (absolute reduction of 1.1 risk factors) and increased
      to ~20% reduction 1 year postintervention (absolute reduction of 1.4 risk
      factors). Risk reduction was primarily due to decreases in dietary glycemic index
      and fasting insulin levels. CONCLUSIONS: Group visits provide an innovative and
      potentially efficacious model of diabetes prevention in multiethnic patients with
      heterogeneous risk factors.

PMID- 24464088
TI  - Abnormal binaural spectral integration in cochlear implant users.
AB  - Bimodal stimulation, or stimulation of a cochlear implant (CI) together with a
      contralateral hearing aid (HA), can improve speech perception in noise However,
      this benefit is variable, and some individuals even experience interference with
      bimodal stimulation. One contributing factor to this variability may be
      differences in binaural spectral integration (BSI) due to abnormal auditory
      experience. CI programming introduces interaural pitch mismatches, in which the
      frequencies allocated to the electrodes (and contralateral HA) differ from the
      electrically stimulated cochlear frequencies. Previous studies have shown that
      some, but not all, CI users adapt pitch perception to reduce this mismatch. The
      purpose of this study was to determine whether broadened BSI may also reduce the
      perception of mismatch. Interaural pitch mismatches and dichotic pitch fusion
      ranges were measured in 21 bimodal CI users. Seventeen subjects with wide fusion
      ranges also conducted a task to pitch match various fused electrode-tone pairs.
      All subjects showed abnormally wide dichotic fusion frequency ranges of 1-4
      octaves. The fusion range size was weakly correlated with the interaural pitch
      mismatch, suggesting a link between broad binaural pitch fusion and large
      interaural pitch mismatch. Dichotic pitch averaging was also observed, in which a
      new binaural pitch resulted from the fusion of the original monaural pitches,
      even when the pitches differed by as much as 3-4 octaves. These findings suggest
      that abnormal BSI, indicated by broadened fusion ranges and spectral averaging
      between ears, may account for speech perception interference and nonoptimal
      integration observed with bimodal compared with monaural hearing device use.

PMID- 24464090
TI  - Epidemiological challenges to the assessment of HIV burdens among key
      populations: respondent-driven sampling, time-location sampling and demographic
      and health surveys.
AB  - PURPOSE OF REVIEW: Measuring the burden of HIV among key populations is subject
      to many challenges. Sufficient quantities of valid HIV prevalence and programme
      coverage data are required to effectively respond to the epidemic. RECENT
      FINDINGS: Ability to validate exposure to unprotected sex through the innovative
      use of prostate-specific antigen provides confirmation of condom use. A new
      weighting scheme based on frequency of venue attendance for time location samples
      should improve validity of data obtained with this method. Two new proportion
      estimators, new diagnostic methods, a new population size estimator and new
      analysis software will provide more robust results from respondent-driven
      sampling (RDS). SUMMARY: Analytical advances have improved the potential quality
      of results from surveys using time location and RDS. However, data from
      sufficient numbers of sites over sufficient number of years are still needed to
      provide clear national pictures of distribution and trends of HIV infection.

PMID- 24464089
TI  - HIV infection among female sex workers in concentrated and high prevalence
      epidemics: why a structural determinants framework is needed.
AB  - PURPOSE OF REVIEW: This article reviews the current state of the epidemiological
      literature on female sex work and HIV from the past 18 months. We offer a
      conceptual framework for structural HIV determinants and sex work that unpacks
      intersecting structural, interpersonal, and individual biological and behavioural
      factors. RECENT FINDINGS: Our review suggests that despite the heavy HIV burden
      among female sex workers (FSWs) globally, data on the structural determinants
      shaping HIV transmission dynamics have only begun to emerge. Emerging research
      suggests that factors operating at macrostructural (e.g., migration, stigma,
      criminalized laws), community organization (e.g., empowerment) and work
      environment levels (e.g., violence, policing, access to condoms HIV testing,
      HAART) act dynamically with interpersonal (e.g., dyad factors, sexual networks)
      and individual biological and behavioural factors to confer risks or protections
      for HIV transmission in female sex work. SUMMARY: Future research should be
      guided by a Structural HIV Determinants Framework to better elucidate the complex
      and iterative effects of structural determinants with interpersonal and
      individual biological and behavioural factors on HIV transmission pathways among
      FSWs, and meet critical gaps in optimal access to HIV prevention, treatment, and
      care for FSWs globally.

PMID- 24464091
TI  - Autism spectrum disorders in XYY syndrome: two new cases and systematic review of
      the literature.
AB  - Abnormalities of the sex chromosomes (47, XXY, 47 XYY, 45,X/46,XY mosaicism) are
      frequently associated with Autism Spectrum Disorders (ASD), but the male
      predisposition to these disorders has not been clearly explained. Previously, the
      role of the X chromosome was considered important in the ASD mainly because
      autistic symptoms were detected in genetic syndromes involving X chromosome
      (fragile X syndrome, Rett syndrome, Klinefelter syndrome). Instead, few studies
      have analyzed the possible role of the Y chromosome in the ASD. This study
      explores the role of the Y chromosome in ASD through a systematic literature
      review about the association between ASD and XYY syndrome and a description of
      two new cases with this association. The literature review considered studies
      published in peer-reviewed journals, included in the MEDLINE and PubMed
      databases, that examined the association between ASD and XYY syndrome. Few
      studies reported the occurrence of ASD in children with XYY karyotype and the
      majority of them did not reported a well-defined autism diagnostic category
      associated with an extra Y chromosome, but several clinical conditions that are
      generically described as language and social impairment. CONCLUSION: This study
      underlines the underestimated role of the Y chromosome in ASD, and we postulate
      that all the ASD associated with the XYY karyotype may presumably fall within
      mild degree of ASD as in our cases.

PMID- 24464092
TI  - Assessment of intraosseous femoral head pressures during cement augmentation of
      the perforated proximal femur nail antirotation blade.
AB  - OBJECTIVES: The benefits of cement augmentation with fixation of osteoporotic
      pertrochanteric fractures have been previously demonstrated. The objective of
      this study was 3-fold: (1) To quantify the intraosseous pressure produced during
      cement augmentation of the perforated proximal femoral nail antirotation (PFNA)
      blades; (2) To assess whether the pressure generated is influenced by the
      injection rate; and (3) To assess the amount of force applied during the
      injection. METHODS: Six pairs of human cadaveric femurs were used in the study. A
      basicervical osteotomy was performed, and the heads were instrumented with the
      PFNA blade. Each pair was randomly assigned into 1 of 2 groups: slow versus rapid
      injection with polymethylmethacrylate (PMMA) cement. In the slow group, the
      augmentation was performed using 6 consecutive 1 mL injections, each over 10
      seconds. In the rapid group, each 1 mL injection was performed over 5 seconds.
      For intraosseous pressure measurements, transmitters were inserted to a depth of
      5 mm at both the superior and inferior apices of the head. The reaction forces on
      the syringe were measured as well. RESULTS: There were no significant differences
      between the slow and rapid injection rates with respect to the peak pressures
      measured at the 6 time points immediately after cement injection. In both groups,
      elevations in pressure were transient and returned to baseline values within 30
      seconds. The highest pressure recorded in the slow group was 37.3 and 30.7 mm Hg
      in the rapid group. The force required after each sequential injection increased
      in both groups; however, significantly higher forces were required to inject
      cement over 5 than 10 seconds (P = 0.036). CONCLUSIONS: This in vitro model is
      the first one to demonstrate that femoral head cement augmentation is associated
      with a small transient increase in intraosseous pressure with sequential fast and
      slow 1 mL injections of up to 6 mL PMMA. We conclude that cement augmentation of
      the perforated PFNA blade carries a low risk of pressure-induced avascular
      necrosis.

PMID- 24464093
TI  - Radiologic outcome and patient-reported function after intramedullary nailing: a
      comparison of the retropatellar and infrapatellar approach.
AB  - OBJECTIVES: The purpose of this study was to compare the patient-reported
      functional outcomes after intramedullary nailing of the tibia through a
      retropatellar or infrapatellar approach. Radiographic assessment of nail entry
      point and accuracy of fracture reduction were included to aid in the
      identification of variables that may explain any difference in patient-reported
      outcomes. DESIGN: A retrospective radiographic and questionnaire-based assessment
      of patient-reported outcomes and complications after tibial nailing for trauma or
      limb reconstruction through a retropatellar or infrapatellar approach. SETTING:
      Regional limb reconstruction unit within a university teaching hospital.
      PATIENTS/PARTICIPANTS: Two consecutive series of 38 patients with intramedullary
      tibial nails inserted through a retropatellar approach, and 36 patients with a
      tibial nail inserted through an infrapatellar approach. INTERVENTION: Tibial nail
      insertion through either a retropatellar or infrapatellar approach. MAIN OUTCOME
      MEASURES: Patient-reported outcomes and complication rates and radiographic
      assessment of fracture reduction and nail insertion entry point. RESULTS: No
      significant difference was seen in Kujala score as a measure of anterior knee
      pain (P = 0.217), either in the physical (P = 0.372) or mental (0.504) components
      of the SF-12 between the groups, although there was a trend toward symptomatic
      intrusive knee pain in the infrapatellar group. A more accurate fracture
      reduction, both in terms of angulation (P = 0.003) and translation (P = 0.010) in
      the coronal plane, was seen in the retropatellar group. The entry point for nail
      insertion was more accurate in both the sagittal (P = 0.011) and coronal (P =
      0.014) planes. CONCLUSIONS: Retropatellar tibial nail insertion is not associated
      with more anterior knee pain when compared with infrapatellar nail insertion but
      is associated with more accurate nail insertion and fracture reduction. LEVEL OF
      EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24464094
TI  - Plate versus nail for distal tibial fractures: a systematic review and meta
      analysis.
AB  - OBJECTIVES: To undertake a systematic review to determine whether there are
      advantages in using plate or nail fixation for distal meta-diaphyseal tibial
      fractures with or without articular involvement. DATA SOURCES: Searches using
      MEDLINE, EMBASE, and Cochrane library. STUDY SELECTION: Studies of parallel group
      design comparing plate or nail fixation for distal tibial fractures. DATA
      EXTRACTION: Information on study methods and outcomes. DATA SYNTHESIS: We
      conducted random effects meta-analysis to evaluate risk of nonunion or delayed
      union, wound complications and superficial infection, deep infection, and
      fracture malalignment. RESULTS: We found 8 studies (n = 455, 4 prospective
      randomized and 4 retrospective cohort) that evaluated plate compared with nail
      for distal tibial fractures. No significant difference was found between the use
      of a plate and nail regarding bone union complications [plate, 5.4%; nail, 8.3%;
      odds ratio (OR), 0.66; 95% confidence interval (CI), 0.28-1.54; I = 0%; P =
      0.34], wound complications including superficial infection (plate, 7.9%; nail,
      3.2%; OR, 1.83; 95% CI, 0.40-8.46; I = 48%; P = 0.44), and deep infection (plate,
      3.5%; nail, 2.8%; OR, 1.32; 95% CI, 0.44-3.91; I = 0%; P = 0.62). We found a
      significantly reduced risk of fracture malalignment with the use of a plate
      compared with a nail (plate, 8.7%; nail, 24.9%; OR, 0.33; 95% CI, 0.17-0.64; I =
      0%; P = 0.001). CONCLUSIONS: Plate fixation compared with intramedullary nailing
      is associated with a reduced risk of fracture malalignment with no differences in
      bone union, wound complications, and superficial infection or deep infection.
      Current evidence might recommend plate over nail unless there are concerns with
      the soft tissues. Additional larger scale multicentre randomized controlled
      trials are required to clarify these issues.

PMID- 24464095
TI  - Prospective nutritional analysis of a diverse trauma population demonstrates
      substantial hypovitaminosis D.
AB  - OBJECTIVES: There are several metabolic factors known to be important for the
      maintenance of bone and muscle function. Causes of deficiency are multifactorial
      and can include such things as geographic region, latitude, and socioeconomic
      factors. The purpose of this study was to determine the prevalence of metabolic
      deficiencies. SETTING: Level 1, urban trauma center. DESIGN: Prospective
      laboratory evaluation. PATIENTS: The subjects included 652 consecutive admits to
      the orthopaedic surgery service between July 1, 2011, and June 30, 2012.
      INTERVENTION: Laboratory evaluation. MAIN OUTCOME MEASUREMENTS: Metabolic and
      endocrine profiles included a serum analysis on all patients. Subject data
      included age, gender, body mass index, month of admission, and type of injury,
      and subjects' self-reported race, alcohol, recreational drug, and tobacco use
      were collected. RESULTS: Six hundred fifty-two subjects with an average age of
      41.2 years were evaluated. After data analysis, only 25-hydroxyvitamin D levels
      were found to be persistently poor across the patient population: 86.2% of
      subjects were insufficient in 25-hydroxyvitamin D (<30 ng/mL), 53.2% were
      deficient (<20 ng/mL), and 14.0% had levels <10 ng/mL (severely deficient); 76.7%
      of the subjects increased skin pigmentation, and the differences in 25
      hydroxyvitamin D levels between races were significantly different. African
      Americans had the highest risk of severe deficiency. 25-Hydroxyvitamin D levels
      were significantly higher during summer months, with men, and with a lower body
      mass index, but there were no differences based on age or substance use.
      Additional laboratory analysis did not reveal significant nutritional deficiency.
      CONCLUSIONS: The prevalence of hypovitaminosis D is widespread. This may
      negatively affect outcomes for orthopaedic patients but would be easily
      correctable. 25-Hydroxyvitamin D serologic analysis should be considered for all
      orthopaedic trauma patients. LEVEL OF EVIDENCE: Prognostic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24464097
TI  - BMP-2 mRNA expression after endothelial progenitor cell therapy for fracture
      healing.
AB  - PURPOSE: Endothelial progenitor cells (EPCs) represent a population of novel
      precursor cells with known ability to participate in angiogenesis. Our previous
      studies have shown that local EPC therapy significantly increased angiogenesis
      and osteogenesis to promote fracture healing in an animal bone defect model.
      However, the cellular and molecular mechanisms by which EPC therapy promotes
      fracture healing remain largely unknown. The purpose of this study was to
      quantify local bone morphogenetic protein (BMP-2) expression after EPC therapy
      for a rat segmental bone defect, in hopes of further defining the potential
      mechanisms by which EPCs promote fracture healing. METHOD: EPCs were isolated
      from the bone marrow of syngeneic rats and cultured ex vivo for 7-10 days before
      transfer to the bone defect. A total of 56 rats were studied. The treatment group
      received 1 * 10 EPCs on a gelfoam scaffold at the bone defect, and control
      animals received gelfoam/saline only. Before euthanasia, radiographs of the femur
      were performed. Animals were euthanized at 1, 2, 3, and 10 weeks, and specimens
      from the fracture gap area were collected, pulverized, and total messenger RNA
      (mRNA) was extracted. BMP-2 mRNA was measured by reverse transcriptase-polymerase
      chain reaction and quantified by VisionWorksLS. All measurements were performed
      in triplicate. RESULTS: All EPC-treated bone defects healed radiographically by
      10 weeks, whereas control-treated defects developed a nonunion. The expression of
      BMP-2 mRNA was significantly elevated in EPC-treated defects relative to controls
      at week 1 (EPC, 0.59 +/- 0.10; control, 0.31 +/- 0.08; P = 0.05), week 2 (EPC,
      0.40 +/- 0.06; control, 0.23 +/- 0.04; P = 0.04), and week 3 (EPC, 0.33 +/- 0.06;
      control, 0.18 +/- 0.03; P = 0.04), but not at week 10 (EPC, 0.31 +/- 0.06;
      control, 0.21 +/- 0.04, P = 0.15). The highest mean expression of BMP-2 in EPC
      treated defects was observed at 1 week, with a progressive decline in BMP-2
      expression noted thereafter. CONCLUSIONS: These findings demonstrate that EPC
      treated bone defects demonstrate both radiographic healing and elevated
      expression of BMP-2 relative to control-treated defects. These results provide
      further insight into the potential mechanisms by which EPC therapy may promote
      fracture healing and provide further evidence to suggest that the trophic actions
      of EPC therapy may be a critical factor in their contribution to fracture
      healing.

PMID- 24464096
TI  - Combined use of low-intensity pulsed ultrasound and rhBMP-2 to enhance bone
      formation in a rat model of critical size defect.
AB  - BACKGROUND: Bone repair is regulated by biological factors and the local
      mechanical environment. We hypothesize that the combined use of low-intensity
      pulsed ultrasound (LIPUS) and recombinant human bone morphogenetic protein-2
      (rhBMP-2) will synergistically or additively enhance bone regeneration in a model
      simulating the more difficult scenarios in orthopaedic traumatology. METHODS:
      Femoral defects in rats were replaced with absorbable collagen sponges carrying
      rhBMP-2 (0, 1.2, 6, or 12 MUg; n = 30). Each group was divided equally to receive
      daily treatment of either LIPUS or sham stimulation. At 4 weeks, new bone
      formation was assessed using quantitative (radiography and microcomputed
      tomography), qualitative (histology), and functional (biomechanical) end points.
      RESULTS: LIPUS with 1.2 MUg of rhBMP-2 significantly improved the radiographic
      healing as compared with its sham control starting as early as 2 weeks.
      Quantitatively, the use of LIPUS with 6 MUg of rhBMP-2 significantly increased
      the bone volume. However, using LIPUS with 12 MUg of rhBMP-2 indicated a
      reduction in callus size, without compromising the bone volume, which was also
      observable histologically, showing organized lamellar bone and repopulated marrow
      in the original defect region. Histologically, 1.2 MUg of rhBMP-2 alone showed
      the presence of uncalcified cartilage in the defect, which was reduced with LIPUS
      treatment. Biomechanically, LIPUS treatment significantly increased the peak
      torsion and stiffness in the 6- and 12 MUg rhBMP-2 groups. CONCLUSIONS: LIPUS
      enhances rhBMP-2-induced bone formation at lower doses (1.2 and 6 MUg) and callus
      maturation at 12-MUg dose delivered on absorbable collagen sponge for bone repair
      in a rat critical-sized femoral segmental defect.

PMID- 24464098
TI  - Hot topics in biomechanically directed fracture fixation.
AB  - The evolution of locking plates and modern nail constructs provides the
      orthopaedic trauma surgeon with a myriad of options with regard to implant
      selection for common fractures. There is a significant amount of biomechanical
      literature comparing modern constructs with those conventionally used. A basic
      understanding of this literature is required to make informed decisions with
      regard to implant selection in the management of these injuries. This article
      reviews the most recent biomechanical literature regarding implant selection and
      application for a variety of commonly treated injuries, including fractures of
      the clavicle, proximal humerus, distal humerus, intertrochanteric hip region,
      distal femur, and bicondylar tibial plateau.

PMID- 24464099
TI  - Resveratrol ameliorates diabetic vascular inflammation and macrophage
      infiltration in db/db mice by inhibiting the NF-kappaB pathway.
AB  - In this study, resveratrol (RSV) - a potent sirtuin 1 activator - was found to
      have beneficial effects on glucolipid metabolism and improve inflammatory
      mediators and markers of oxidative stress. Diabetic (db/db) mice and non-diabetic
      C57BL/6J mice were used in the study. The db/db mice were treated with or without
      0.3% RSV mixed with chow for 8 weeks. Dietary RSV significantly lowered blood
      glucose, plasma lipid and free fatty acid levels in db/db mice. RSV markedly
      inhibited the expression of intercellular adhesion molecule-1 (ICAM-1),
      endothelial vascular cell adhesion molecule-1 (VCAM-1) and monocyte
      chemoattractant protein-1 (MCP-1) in the aorta and the blood plasma of db/db mice
      (p < 0.05). Levels of mac-3-positive macrophages (measure of the infiltration of
      activated macrophages) were lower in RSV-treated diabetic mice than in their
      untreated counterparts (p < 0.05). RSV treatment reduced the activity of the
      transcriptional regulator nuclear factor kappa B (NF-kappaB) in aortic tissues (p
      < 0.05). Thus, RSV treatment reduced ICAM-1, VCAM-1 and MCP-1 expression in the
      aorta and ICAM-1, VCAM-1 and MCP-1 levels in the plasma of diabetic mice. Since
      dietary supplementation with RSV also reduced NF-kappaB activities in the aorta,
      the therapeutic effects of RSV might be associated with the downregulation of NF
      kappaB. 

PMID- 24464100
TI  - Identification of low-frequency and rare sequence variants associated with
      elevated or reduced risk of type 2 diabetes.
AB  - Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114
      Icelandic cases and 267,140 controls followed by testing in Danish and Iranian
      samples, we discovered 4 previously unreported variants affecting risk of type 2
      diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2,
      rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 * 10(
      21)) and is correlated with increased CCND2 expression. Notably, this variant is
      also associated with both greater height and higher body mass index (1.17 cm per
      allele, P = 5.5 * 10(-12) and 0.56 kg/m(2) per allele, P = 6.5 * 10(-7),
      respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly
      (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately
      higher risk of T2D (OR = 1.23, P = 3.9 * 10(-10) and OR = 1.47, P = 1.7 * 10(-5),
      respectively), and a rare (0.20%) frameshift variant in PDX1, encoding
      p.Gly218Alafs*12, associates with high risk of T2D (OR = 2.27, P = 7.3 * 10(-7)).

PMID- 24464102
TI  - Zn-bis-glutathionate is the best co-substrate of the monomeric phytochelatin
      synthase from the photosynthetic heavy metal-hyperaccumulator Euglena gracilis.
AB  - The phytochelatin synthase from photosynthetic Euglena gracilis (EgPCS) was
      analyzed at the transcriptional, kinetic, functional, and phylogenetic levels.
      Recombinant EgPCS was a monomeric enzyme able to synthesize, in the presence of
      Zn(2+) or Cd(2+), phytochelatin2-phytochelatin4 (PC2-PC4) using GSH or S-methyl
      GS (S-methyl-glutathione), but not gamma-glutamylcysteine or PC2 as a substrate.
      Kinetic analysis of EgPCS firmly established a two-substrate reaction mechanism
      for PC2 synthesis with Km values of 14-22 mM for GSH and 1.6-2.5 MUM for metal
      bis-glutathionate (Me-GS2). EgPCS showed the highest Vmax and catalytic
      efficiency with Zn-(GS)2, and was inactivated by peroxides. The EgPCS N-terminal
      domain showed high similarity to that of other PCSases, in which the typical
      catalytic core (Cys-70, His-179 and Asp-197) was identified. In contrast, the C
      terminal domain showed no similarity to other PCSases. An EgPCS mutant comprising
      only the N-terminal 235 amino acid residues was inactive, suggesting that the C
      terminal domain is essential for activity/stability. EgPCS transcription in
      Euglena cells was not modified by Cd(2+), whereas its heterologous expression in
      ycf-1 yeast cells provided resistance to Cd(2+) stress. Phylogenetic analysis of
      the N-terminal domain showed that EgPCS is distant from plants and other
      photosynthetic organisms, suggesting that it evolved independently. Although
      EgPCS showed typical features of PCSases (constitutive expression; conserved N
      terminal domain; kinetic mechanism), it also exhibited distinct characteristics
      such as preference for Zn-(GS)2 over Cd-(GS)2 as a co-substrate, a monomeric
      structure, and ability to solely synthesize short-chain PCs, which may be
      involved in conferring enhanced heavy-metal resistance. 

PMID- 24464101
TI  - Evolution and transmission of drug-resistant tuberculosis in a Russian
      population.
AB  - The molecular mechanisms determining the transmissibility and prevalence of drug
      resistant tuberculosis in a population were investigated through whole-genome
      sequencing of 1,000 prospectively obtained patient isolates from Russia. Two
      thirds belonged to the Beijing lineage, which was dominated by two homogeneous
      clades. Multidrug-resistant (MDR) genotypes were found in 48% of isolates overall
      and in 87% of the major clades. The most common rpoB mutation was associated with
      fitness-compensatory mutations in rpoA or rpoC, and a new intragenic compensatory
      substitution was identified. The proportion of MDR cases with extensively drug
      resistant (XDR) tuberculosis was 16% overall, with 65% of MDR isolates harboring
      eis mutations, selected by kanamycin therapy, which may drive the expansion of
      strains with enhanced virulence. The combination of drug resistance and
      compensatory mutations displayed by the major clades confers clinical resistance
      without compromising fitness and transmissibility, showing that, in addition to
      weaknesses in the tuberculosis control program, biological factors drive the
      persistence and spread of MDR and XDR tuberculosis in Russia and beyond. 

PMID- 24464103
TI  - EVI1 expression in childhood acute lymphoblastic leukaemia is not restricted to
      MLL and BCR/ABL rearrangements and is influenced by age.

PMID- 24464104
TI  - Embodying recovery: a qualitative study of peer work in a consumer-run service
      setting.
AB  - The use of peer support for persons with mental illness has been gaining force.
      While research has demonstrated the benefits of peer support, few studies have
      investigated the qualitative characteristics of how peer support aids persons
      recovering from mental illness. Therefore, this study sought to clarify the
      characteristics that constitute peer support and its contribution to recovery. We
      conducted ethnographic fieldwork and semi-structured interviews with nine peer
      advocates at a consumer-run organization in New York City, and identified three
      themes that describe how peer support influences recovery: transforming
      experience into expertise, understanding the mechanics of peer support, and
      launching peers towards their own recovery. Peer support plays a critical role in
      helping clients move beyond their patient role to an empowered sense of
      personhood. Additionally, the value of peer support highlights current
      deficiencies within the mental health system and how a bolder shift towards
      recovery might repair them. 

PMID- 24464105
TI  - Intensive care in a general hospital: demographics, utilization and outcomes.
AB  - INTRODUCTION: Intensive care units (ICU) in Irish academic centres are known to
      fare as well as their international counterparts. Our aim in this study was to
      characterise the role and outcomes of an ICU in a smaller Irish hospital and to
      compare these to international best practice. METHODS: We reviewed admissions of
      patients to the ICU of St. Luke's Hospital, Kilkenny. Patient demographics,
      indications for admission, and outcomes were all recorded and analysed.
      Sequential organ failure assessment (SOFA) scores were calculated. RESULTS: Forty
      three patients were included in our study, 33 (76.7 %) of which were emergency
      admissions. Median length of stay was 2 days. The observed mortality rate in our
      cohort was 20.9 %. The median SOFA score in patients admitted was 7. Higher
      median SOFA scores on admission were predictive of mortality. The ICU occupancy
      rate during the duration of our study was 98 %, with only 15 (35.7 %) of
      admissions to ICU occurring within core working hours. CONCLUSION: Critical care
      can be provided safely and in line with current best practice in smaller Irish
      hospitals. There is a cohort of patients for whom care may be best provided in a
      tertiary centre, how best to provide for these patients will likely be achieved
      by early identification (e.g. with SOFA score). Bed capacity issues remain
      problematic.

PMID- 24464106
TI  - Yoga and meditation in cardiovascular disease.
AB  - Yoga is a holistic mind-body intervention aimed at physical, mental, emotional
      and spiritual well being. Several studies have shown that yoga and/or meditation
      can control risk factors for cardiovascular disease like hypertension, type II
      diabetes and insulin resistance, obesity, lipid profile, psychosocial stress and
      smoking. Some randomized studies suggest that yoga/meditation could retard or
      even regress early and advanced coronary atherosclerosis. A recent study suggests
      that transcendental meditation may be extremely useful in secondary prevention of
      coronary heart disease and may reduce cardiovascular events by 48% over a 5-year
      period. Another small study suggests that yoga may be helpful in prevention of
      atrial fibrillation. However, most studies have several limitations like lack of
      adequate controls, small sample size, inconsistencies in baseline and different
      methodologies, etc. and therefore large trials with improved methodologies are
      required to confirm these findings. However, in view of the existing knowledge
      and yoga being a cost-effective technique without side effects, it appears
      appropriate to incorporate yoga/meditation for primary and secondary prevention
      of cardiovascular disease.

PMID- 24464108
TI  - The RCN is not taking the Francis Report lightly.

PMID- 24464107
TI  - Transient impact of baseline depression on mortality in patients with stable
      coronary heart disease during long-term follow-up.
AB  - OBJECTIVE: The objective of this prospective study was to determine the impact of
      depressive symptoms on long-term survival in coronary heart disease (CHD)
      patients treated with intracoronary stenting. METHODS: Four hundred and seventy
      patients completed the Hospital Anxiety and Depression Scale (HADS) before
      undergoing stent implantation and were followed over a 5-year period. Survival
      data were collected from n = 462 participants (98.3 %). A cut-off >=8 on the HADS
      depression subscale was used to indicate probable clinical levels of depression.
      RESULTS: All-cause mortality rates differed significantly between depressed and
      non-depressed patients at 2-year follow-up, as 6 out of 98 subjects with elevated
      HADS-D scores (6.1 %), but only 8 out of 364 (2.2 %) patients with normal HADS-D
      scores had died [odds ratio = 2.9, 95 % confidence interval (95 % CI) = 1.0-8.6,
      p = 0.044]. In a Cox regression model adjusted for sociodemographic and clinical
      parameters, positive HADS-D scores [hazard ratio (HR) = 4.3, 95 % CI = 1.2-15.4,
      p = 0.025], body-mass index (HR = 0.8, 95 % CI = 0.7-1.0, p = 0.040) and stent
      length (HR = 1.1, 95 % CI = 1.0-1.1, p = 0.042) independently predicted 2-year
      survival. From the third to the fifth year after index PCI, the frequency of
      deaths in the depressed patients' group did not significantly differ from that
      observed in non-depressed patients (5.5 % versus 7.0 %, p = 0.607), and the
      predictive role of baseline HADS-D scores for survival was lost. CONCLUSION: In
      CHD patients, self-rated depressive symptoms at baseline were negatively linked
      to survival at 2-year follow-up, but failed to predict mortality 3 years later.
      Thus, in contrast to other well-established risk factors, the prognostic value of
      depression for predicting adverse outcome may be temporarily limited. The
      mechanisms behind this transient effect need further study.

PMID- 24464109
TI  - The case for flu vaccination for health professionals.

PMID- 24464110
TI  - Nurse screening for neuropathic pain in postoperative patients.
AB  - This study was designed to audit nurse assessment and documentation for
      neuropathic pain in postoperative patients. The audit focused on recorded signs
      of neuropathic pain in the immediate postoperative period. Nurses were educated
      on how to screen patients for neuropathic signs using the validated and reliable
      7-item DN4. Data were obtained from 450 patient charts from the thoracic,
      orthopaedic and spinal units. Of the 450 patient charts reviewed, 423 included a
      record of nurse screening of neuropathic pain signs. Screening by nurses found
      24% (n=102) of the patients reported between one and four signs of neuropathic
      pain within the first 3 days following their surgery. This study demonstrated
      that the incorporation of the 7-item DN4 neuropathic pain assessment tool within
      the generic pain chart enabled nurses to regularly screen postoperative patients
      for signs of neuropathic pain in the immediate postoperative period. 

PMID- 24464111
TI  - Re-examining the basis for ethical dementia care practice.
AB  - Ethical nursing practice is an important component of quality dementia care. To
      be ethically competent, and to acquire the language, knowledge and skills
      required to explore and resolve ethical dilemmas in practice, the nurse needs an
      understanding of ethics and of the theory behind ethical decision-making.
      Traditional theories of ethics and ethical principles are commonly used to
      explore the dilemmas faced in dementia care practice. While these theories remain
      influential in healthcare practice, more contemporary ethical theories are
      equally relevant to the examination of the ordinary and extraordinary ethical
      dilemmas that present in conditions such as dementia. In this article, the
      ethical considerations central to effective dementia care nursing will be
      examined. 

PMID- 24464112
TI  - Interventions in exclusive breastfeeding: a systematic review.
AB  - Now recognised as a worldwide public health issue, the significance of promoting
      and encouraging exclusive breastfeeding (EBF) has been acknowledged by the World
      Health Organization (WHO) and the United Nations Children's Fund (UNICEF).
      Documented policies about the importance of facilitating the support of
      breastfeeding women is currently receiving worldwide recognition (WHO, 2011; WHO
      and UNICEF, 2003). This literature review will examine provision of support
      mechanisms for breastfeeding mothers, focusing on peer support in encouraging the
      starting and maintaining of EBF. Consideration will also be given to any barriers
      that may prevent higher success rates, as cultural and educational factors may
      have a significant impact on the starting and maintaining of EBF. These factors
      must be considered when starting support groups, networks or activities that aim
      to address this significant public health issue. 

PMID- 24464113
TI  - HIV diagnoses are in our hands.

PMID- 24464114
TI  - Determining fever in children: the search for an ideal thermometer.
AB  - Body temperature measurement is most commonly taken to confirm the presence or
      absence of fever. Many decisions concerning the investigation and treatment of
      children are based on the results of temperature measurement alone. Determining
      the presence of fever in young children is particularly important. A missed fever
      is serious, but a false-positive fever reading can result in unnecessary septic
      workups. The axillary, rectal, oral and tympanic membrane sites are most commonly
      used to record body temperature, and electronic and infrared thermometers are the
      devices most commonly used. Each site and device has numerous advantages and
      disadvantages, which are described in this article. The search for the means of
      measuring body temperature that best combines accuracy, speed, convenience,
      safety and cost-effectiveness goes on. The infrared thermometer and the tympanic
      site appear to offer such a combination. Electronic thermometers are also
      suitable when used orally or at the axilla in newborn babies. 

PMID- 24464115
TI  - Patient experiences of enhanced recovery after surgery (ERAS).
AB  - Enhanced recovery after surgery (ERAS) is a multimodal pathway whose strong
      evidence base is changing the methods used to care for patients before, during
      and after surgery. As a result, patients are being safely discharged at a much
      earlier stage than has previously been thought possible. Literature concentrates
      on the surgical and economical benefits of ERAS. There is a lack of research into
      the patients' perspective of the programme. This study used semi-structured
      interviews to investigate issues of significance to ERAS patients. The issues
      were grouped into themes: information provision, inpatient experiences, home
      recovery experiences (i.e. home convalescence) and psychological and emotional
      experiences. Although participants reported many good aspects of their ERAS
      experience, the findings highlighted the need for improvement particularly with
      regard to post-discharge support from both community services and hospital follow
      up. 

PMID- 24464116
TI  - Francis report: the government accepts recommendations.

PMID- 24464117
TI  - CQC develops new criteria for quality and safety of care.

PMID- 24464118
TI  - Health and safety in the NHS.
AB  - Accidents at work cost the NHS some billion pounds every year. Over half of these
      accidents are due to avoidable slips and falls-the most common cause of claim for
      compensation faced by the NHS. Under the Management of Health and Safety at Work
      Regulations 1999, the NHS as an employer and nurses as employees have a legal
      obligation to manage health and safety and to ensure that others are not put at
      risk by work-related activities. The first of a series, this article on health
      and safety law sets out the duties imposed on NHS organisations and their
      employees. 

PMID- 24464119
TI  - Clinical supervision: from staff nurse to nurse consultant. Part 12: series
      summary.

PMID- 24464120
TI  - NHS nurses' fight against infection.

PMID- 24464121
TI  - Stabilized hyaluronic acid gel for volume restoration and contouring of the
      buttocks: 24-month efficacy and safety.
AB  - BACKGROUND: Stabilized hyaluronic acid (HA) of nonanimal origin manufactured
      using the patented NASHA(r) technology has been developed for use in body
      shaping. This study was performed to assess the safety and efficacy of stabilized
      HA gel when used for volume restoration and contouring of the buttocks. METHODS:
      Subjects 20 years of age or older seeking buttock augmentation were recruited to
      this noncomparative multicenter study (NCT01331408). Gel at a maximum volume of
      400 mL per subject was injected during one or two treatment visits. Safety and
      efficacy assessments (24-month follow-up evaluation) included adverse event (AE)
      reporting, aesthetic improvement (Global Aesthetic Improvement Scale [GAIS]), and
      subject satisfaction. RESULTS: In this study, 61 subjects received a mean total
      volume of 340 mL (range 200-420 mL) of stabilized HA gel. According to subject
      GAIS assessment, buttock appearance was rated as "improved," "much improved," or
      "very much improved" by 80, 68, 42, and 40% of subjects after 6, 12, 18, and 24
      months, respectively. Subject satisfaction with buttock size, shape, firmness,
      and general appearance was higher than before treatment at all the time points,
      with a peak of 70% of the subjects satisfied 1 month after treatment. During the
      24 months, no unexpected or serious treatment-related AEs occurred. One subject
      experienced gel dislocation to the sacral area. CONCLUSIONS: The data show that
      stabilized HA gel is a safe and effective treatment for temporary aesthetic
      augmentation of the buttocks. Although the substance degrades over time, a good
      proportion of the subjects still rated their buttocks as improved (40%) and
      expressed satisfaction (33%) 24 months after treatment. 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- 24464123
TI  - Subciliary augmentation of the lower eyelid in Asians using a deep temporal
      fascia graft: a preliminary report.
AB  - BACKGROUND: Pretarsal fullness of the lower eyelid has recently gained popularity
      in the Asian population. Hyaluronic acid injection is a simple, nonsurgical
      method for creating pretarsal fullness of the lower eyelid, but the effects last
      only 6-12 months. A need exists for a surgical procedure with long-term effects.
      We describe the use of a deep temporal fascia graft for subciliary augmentation
      of the lower eyelid. METHODS: Between September 2009 and October 2011, seven
      Japanese patients underwent subciliary augmentation of the lower eyelid. This
      retrospective study was conducted on four of the seven patients who were followed
      for more than 1 year. A skin incision of approximately 1 cm was made at the
      lateral canthus along the subciliary crease of the lower eyelid and the skin was
      undermined to create a subcutaneous tunnel. A stab incision was then made 2 mm
      below the ciliary margin near the level of the lower lacrimal punctum. The
      orbicularis oculi muscle was incised under the skin incision at the lateral
      canthus, and the stump of the incised muscle was suspended to the periosteum of
      the lateral orbital rim. A deep temporal fascia graft was placed in the
      undermined subcutaneous plane of the lower eyelid. RESULTS: Lower-eyelid
      pretarsal fullness was maintained at more than 1 year after surgery. The eyelids
      regained a natural appearance, and the patients were highly satisfied.
      Morphometric measurements demonstrated increased projection and width of the
      lower-eyelid pretarsal fullness. CONCLUSIONS: Deep temporal fascia grafting is
      safe and reliable for subciliary augmentation of the lower eyelid. LEVEL OF
      EVIDENCE V: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24464122
TI  - Vibration anesthesia for the reduction of pain with facial dermal filler
      injections.
AB  - BACKGROUND: Vibration anesthesia is an effective pain-reduction technique for
      facial cosmetic injections. The analgesic effect of this method was tested in
      this study during facial dermal filler injections. The study aimed to evaluate
      the safety and efficacy of vibration anesthesia for these facial injections.
      METHODS: This prospective study analyzed 41 patients who received dermal filler
      injections to the nasolabial folds, tear troughs, cheeks, and other facial sites.
      The injections were administered in a randomly assigned split-face design. One
      side of the patient's face received vibration together with dermal filler
      injections, whereas the other side received dermal filler injections alone. The
      patients completed a posttreatment questionnaire pertaining to injection pain,
      adverse effects, and preference for vibration with future dermal filler
      injections. RESULTS: The patients experienced both clinically and statistically
      significant pain reduction when a vibration stimulus was co-administered with the
      dermal filler injections. No adverse events were reported. The majority of the
      patients (95 %) reported a preference for vibration anesthesia with subsequent
      dermal filler injections. CONCLUSIONS: Vibration is a safe and effective method
      of achieving anesthesia during facial dermal filler injections. 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- 24464124
TI  - Enhanced lentiviral vector production in 293FT cells expressing Siglec-9.
AB  - Siglecs, sialic acid-recognizing Ig-superfamily lectins, regulate various aspects
      of immune responses, and have also been shown to induce the endocytosis of
      binding materials such as anti-Siglec antibodies or sialic acid-harboring
      bacteria. In this study, we demonstrated that the expression of Siglec-9 enhanced
      the transfection efficiency of several cell lines such as macrophage RAW264 and
      non-hematopoietic 293FT cells. We applied this finding to the production of a
      lentiviral vector in which cells were transfected simultaneously with multiple
      vectors, and achieved a twice increase in viral production levels. Furthermore,
      293FT cells expressing lectin-defective Siglec-9 produced three- to seven-fold
      higher titer of viral vector compared with parental 293FT cells. These results
      suggest that Siglec-9 enhanced lentiviral vector production in a lectin
      independent manner. 

PMID- 24464125
TI  - Isolation and characterization of OsMY1, a putative partner of OsRac5 from Oryza
      sativa L.
AB  - OsRac5 belongs to the rice Rho of plants family, and acts as the molecular switch
      in the signal pathway which is pivotally involved in the rice fertility control.
      One of its putative partners, OsMY1, was isolated by yeast two-hybrid screening
      from rice panicle cDNA library. Bioinformatics analysis shows that OsMY1 contains
      a coiled-coil domain which generally appeared in the partners of Rho GTPases. By
      yeast two-hybrid assay, it is confirmed that OsMY1 binds both the wild type (WT)
      and constitutively active (CA) OsRac5, but does not interact with dominantly
      negative OsRac5. In addition, the interactions between OsMY1 and WT-OsRac5 or CA
      OsRac5 in vivo are demonstrated by bimolecular fluorescence complementation
      assay. Using PCR-mediated sequence deletion and point mutation of OsMY1, the
      interaction between OsMY1 and OsRac5 was identified to be mediated by the coiled
      coil domain in OsMY1, and their binding was quantified by O-nitro-phenyl-beta-D
      galactopyranoside assay. Real-time PCR shows that OsMY1 and OsRac5 are
      coordinately expressed in rice leaves and panicles with similar expression
      patterns. Our results suggest that OsMY1 is an important target of OsRac5 and
      that these two genes are involved in the same biological processes in rice growth
      and development. 

PMID- 24464126
TI  - Lack of association of IGFBP-3 gene polymorphisms with colorectal cancer:
      evidence from 17,380 subjects.
AB  - Published data on the association of IGFBP-3 gene polymorphisms with colorectal
      cancer (CRC) are inconclusive. We conducted a meta-analysis to derive a precise
      estimation of the association. A literature search that included PubMed, EMBASE,
      Elsevier Science Direct and China National Knowledge Infrastructure was conducted
      to identify studies up to October 15, 2013. Summary odds ratios (ORs) and 95 %
      confidence intervals (95 % CIs) for IGFBP-3 gene polymorphisms and CRC were
      calculated in a fixed effect model or a random effect model. We identified 10
      separate studies including 7,000 cases and 10,380 controls using search. Meta
      analysis was performed for two IGFBP-3 gene polymorphisms (rs2854744 and
      rs2854746). We found no association between IGFBP-3 gene rs2854744 polymorphism
      and CRC (P > 0.05). Similar result was observed between rs2854746 polymorphism
      and CRC (P > 0.05). This meta-analysis demonstrates that there is no association
      of IGFBP-3 gene rs2854744 and rs2854746 polymorphisms with CRC risk.

PMID- 24464127
TI  - Cloning and expression analysis of the gene encoding fibrinogen-like protein A, a
      novel regeneration-related protein from Apostichopus japonicus.
AB  - Fibrinogen-like protein A (FGLA), a member of the fibrinogen-related protein
      superfamily, exists in different tissues of vertebrates and invertebrates. FGLA
      plays crucial roles including innate immune response, blood clotting and
      regeneration. In this study, the fibrinogen-like protein A (fglA) was cloned from
      Apostichopus japonicus using rapid amplification of cDNA ends PCR techniques. The
      cDNA sequence of fglA is 1,524 bp with a 849 bp open reading frame encoding a
      polypeptide of 282 amino acids, with an N-terminal signal peptide and a conserved
      C-terminal domain. Bioinformatic analysis revealed that the predicted molecular
      weight of the whole protein is 31.9 kDa and it has an isoelectric point of 5.64.
      In-situ hybridization demonstrated that fglA is widely distributed in body wall,
      intestines, longitudinal muscles and respiratory tree. The expression levels of
      fglA during different regeneration stages in the body wall, intestine and
      respiratory trees were analyzed by real-time PCR. The expression of fglA
      gradually increased within 1 h in body wall, and reached a plateau before
      decreasing to the basal level. This indicates that fglA is associated with the
      regeneration of Apostichopus japonicus.

PMID- 24464128
TI  - Association of mutation and hypermethylation of p21 gene with susceptibility to
      breast cancer: a study from north India.
AB  - p21 gene located at chromosome 6p21.2 is a possible tumour suppressor gene
      involved in the pathogenesis of breast cancer. Both genetic and epigenetic
      alterations in p21 have been implicated in breast carcinoma. In the present
      study, our main aim was to study the impact of these two kinds of alterations of
      p21 gene in Indian female breast cancer patients. A total of 150 female breast
      cancer patients of north India were screened by PCR-SSCP followed by direct
      sequencing and methylation specific PCR. Mutational screening of p21 gene
      revealed significant amount of mutations [32.66% (49/150)] in exon 2, whereas p21
      promoter was found hypermethylated in 42 of 150 (28%) breast cancer patients in
      our population. The intriguing feature of the study was the G>T transition
      (GAG>TAG) at codon 107 and the A>C transition (AGC>CGC) at codon 146 possibly
      rendering p21 completely ineffective in its anti- proliferative activity. Our
      results suggest a significant association between the mutational and
      hypermethylation profile of p21 gene. Therefore, we show for the first time that
      the significant association of p21 mutation and hypermethylation leads to the
      complete inactivation of p21 gene in Indian female breast cancer patients.
      Complete silencing of the p21 gene seems to be the result not only of genetic
      alterations but also of epigenetic modification.

PMID- 24464129
TI  - Molecular cloning and characterization of the promoter region of the porcine
      apolipoprotein E gene.
AB  - Apolipoprotein E (APOE), a component of lipoproteins plays an important role in
      the transport and metabolism of cholesterol, and is associated with
      hyperlipoproteinemia and Alzheimer's disease. In order to further understand the
      characterization of APOE gene, the promoter of APOE gene of Landrace pigs was
      analyzed in the present study. The genomic structure and amino acid sequence in
      pigs were analyzed and found to share high similarity in those of human but low
      similarity in promoter region. Real-time PCR revealed the APOE gene expression
      pattern of pigs in diverse tissues. The highest expression level was observed in
      liver, relatively low expression in other tissues, especially in stomach and
      muscle. Furthermore, the promoter expressing in Hepa 1-6 was significantly better
      at driving luciferase expression compared with C2C12 cell. After analysis of
      porcine APOE gene promoter regions, potential transcription factor binding sites
      were predicted and two GC signals, a TATA box were indicated. Results of promoter
      activity analysis indicated that one of potential regulatory elements was located
      in the region -669 to -259, which was essential for a high expression of the APOE
      gene. Promoter mutation and deletion analysis further suggested that the C/EBPA
      binding site within the APOE promoter was responsible for the regulation of APOE
      transcription. Electrophoretic mobility shift assays also showed the binding site
      of the transcription factor C/EBPA. This study advances our knowledge of the
      promoter of the porcine APOE gene. 

PMID- 24464132
TI  - D-dimer value more than 3.6 MUg/ml is highly possible existence deep vein
      thrombosis.
AB  - OBJECTIVE: The present study aimed to establish whether a more optimal cutoff
      value for D-dimer testing could definitively rule out acute deep vein thrombosis
      (DVT). METHODS: Between April 2009 and March 2010, 190 referral patients
      suspected to have DVT were assessed by the D-dimer assay. Additionally,
      ultrasonography (US) and computed tomography (CT) imaging were performed to
      detect thrombosis. RESULTS: DVT was identified in 47 patients (24%). The average
      D-dimer level in patients with DVT was 17.6+/-22.4 MUg/ml, and was significantly
      lower (p=0.035),] at 2.7+/-4.2 MUg/ml, in those without DVT. On the basis of
      receiver operating curve analysis, the specificity of the D-dimer for diagnosing
      DVT increased from 40% to 78.3%, and its sensitivity reached 93.8%, when the
      cutoff value for the assay was set at 3.6 MUg/ml. CONCLUSIONS: D-dimer value over
      3.6 MUg/ml was highly prognostic for DVT.

PMID- 24464130
TI  - The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for
      the induction of immunotolerance.
AB  - The maintenance of immunological tolerance requires the deletion of self-reactive
      T cells in the thymus. The expression of genes encoding tissue-specific antigens
      (TSAs) by thymic epithelial cells is critical for this process and depends on
      activity of the transcriptional regulator Aire; however, the molecular mechanisms
      Aire uses to target loci encoding TSAs are unknown. Here we identified two Aire
      interacting proteins known to be involved in gene repression, ATF7ip and MBD1,
      that were required for Aire's targeting of loci encoding TSAs. Moreover, Mbd1(-/
      ) mice developed pathological autoimmunity and had a defect in Aire-dependent
      thymic expression of genes encoding TSAs, which underscores the importance of
      Aire's interaction with the ATF7ip-MBD1 protein complex in maintaining central
      tolerance. 

PMID- 24464131
TI  - K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1
      induced production of chemokines CXCL10 and CCL5.
AB  - Although interleukin 1 (IL-1) induces expression of the transcription factor IRF1
      (interferon-regulatory factor 1), the roles of IRF1 in immune and inflammatory
      responses and mechanisms of its activation remain elusive. Here we found that
      IRF1 was essential for IL-1-induced expression of the chemokines CXCL10 and CCL5,
      which recruit mononuclear cells into sites of sterile inflammation. Newly
      synthesized IRF1 acquired Lys63 (K63)-linked polyubiquitination mediated by the
      apoptosis inhibitor cIAP2 that was enhanced by the bioactive lipid S1P. In
      response to IL-1, cIAP2 and the sphingosine kinase SphK1 (the enzyme that
      generates S1P) formed a complex with IRF1, which led to its activation. Thus, IL
      1 triggered a hitherto unknown signaling cascade that controlled the induction of
      IRF1-dependent genes that encode molecules important for sterile inflammation. 

PMID- 24464133
TI  - A case of acute pancreatitis following endoscopic biopsy of the ampulla of Vater.
AB  - Ampullary tumors are diagnosed by endoscopic biopsy of the ampulla of Vater. We
      encountered a rare case of acute pancreatitis following endoscopic biopsy of the
      ampulla. A 53-year-old man referred to our hospital for detailed examination of a
      suspected tumor of the ampulla of Vater. We conducted endoscopic biopsy from the
      ampulla. He developed severe abdominal pain four hours after the procedure. The
      serum amylase and serum lipase were elevated and abdominal computed tomography
      (CT) revealed pancreatic enlargement and diffuse stranding of the peri-pancreatic
      fat, compatible with the findings of acute pancreatitis. We diagnosed the patient
      as having acute pancreatitis caused by endoscopic biopsy of the ampulla of Vater.
      Conservative therapy improved his condition, however, a large pancreatic walled
      off necrosis (WON) developed. Therefore, we performed endoscopic ultrasonography
      (EUS)-guided cyst drainage on the 74th day after admission. The WON diminished
      gradually in size and the symptoms disappeared, and the patient was discharged in
      good physical condition on the 137th day after admission. In this case, the
      ampullary biopsy may have caused mucosal edema or intraductal hematoma, resulting
      in pancreatic duct obstruction. It is important for endoscopists both to be aware
      of this potential complication following endoscopic biopsy of the ampulla and to
      inform the patients about possible complications of this procedure. 

PMID- 24464134
TI  - Comparison of the pi-stacking properties of purine versus pyrimidine residues.
      Some generalizations regarding selectivity.
AB  - Aromatic-ring stacking is pronounced among the noncovalent interactions occurring
      in biosystems and therefore some pertinent features regarding nucleobase residues
      are summarized. Self-stacking decreases in the series adenine > guanine >
      hypoxanthine > cytosine ~ uracil. This contrasts with the stability of binary
      (phen)(N) adducts formed by 1,10-phenanthroline (phen) and a nucleobase residue
      (N), which is largely independent of the type of purine residue involved,
      including (N1)H-deprotonated guanine. Furthermore, the association constant for
      (phen)(A)(0/4-) is rather independent of the type and charge of the adenine
      derivative (A) considered, be it adenosine or one of its nucleotides, including
      adenosine 5'-triphosphate (ATP(4-)). The same holds for the corresponding adducts
      of 2,2'-bipyridine (bpy), although owing to the smaller size of the aromatic-ring
      system of bpy, the (bpy)(A)(0/4-) adducts are less stable; the same applies
      correspondingly to the adducts formed with pyrimidines. In accord herewith,
      [M(bpy)](adenosine)(2+) adducts (M(2+) is Co(2+), Ni(2+), or Cu(2+)) show the
      same stability as the (bpy)(A)(0/4-) ones. The formation of an ionic bridge
      between -NH3 (+) and -PO3 (2-), as provided by tryptophan [H(Trp)(+/-)] and
      adenosine 5'-monophosphate (AMP(2-)), facilitates recognition and stabilizes the
      indole-purine stack in [H(Trp)](AMP)(2-). Such indole-purine stacks also occur in
      nature. Similarly, the formation of a metal ion bridge as occurs, e.g., between
      Cu(2+) coordinated to phen and the phosphonate group of 9-[2
      (phosphonomethoxy)ethyl]adenine (PMEA(2-)) dramatically favors the intramolecular
      stack in Cu(phen)(PMEA). The consequences of such interactions for biosystems are
      discussed, especially emphasizing that the energies involved in such isomeric
      equilibria are small, allowing Nature to shift such equilibria easily. 

PMID- 24464135
TI  - Assessment of Jatropha curcas L. biodiesel seed cake toxicity using the zebrafish
      (Danio rerio) embryo toxicity (ZFET) test.
AB  - Consequent to the growing demand for alternative sources of energy, the seeds
      from Jatropha curcas remain to be the favorite for biodiesel production. However,
      a significant volume of the residual organic mass (seed cake) is produced during
      the extraction process, which raises concerns on safe waste disposal. In the
      present study, we assessed the toxicity of J. curcas seed cake using the
      zebrafish (Danio rerio) embryotoxicity test. Within 1-h post-fertilization (hpf),
      the fertilized eggs were exposed to five mass concentrations of J. curcas seed
      cake and were followed through 24, 48, and 72 hpf. Toxicity was evaluated based
      on lethal endpoints induced on zebrafish embryos namely egg coagulation, non
      formation of somites, and non-detachment of tail. The lowest concentration
      tested, 1 g/L, was not able to elicit toxicity on embryos whereas 100 % mortality
      (based also on lethal endpoints) was recorded at the highest concentration at
      2.15 g/L. The computed LC50 for the J. curcas seed cake was 1.61 g/L. No further
      increase in mortality was observed in the succeeding time points (48 and 72 hpf)
      indicating that J. curcas seed cake exerted acute toxicity on zebrafish embryos.
      Sublethal endpoints (yolk sac and pericardial edema) were noted at 72 hpf in
      zebrafish embryos exposed to higher concentrations. The observed lethal endpoints
      induced on zebrafish embryos were discussed in relation to the active principles,
      notably, phorbol esters that have remained in the seed cake even after
      extraction. 

PMID- 24464136
TI  - Brown rust disease control in winter wheat: II. Exploring the optimization of
      fungicide sprays through a decision support system.
AB  - A decision support system (DSS) involving an approach for predicting wheat leaf
      rust (WLR) infection and progress based on night weather variables (i.e., air
      temperature, relative humidity, and rainfall) and a mechanistic model for leaf
      emergence and development simulation (i.e., PROCULTURE) was tested in order to
      schedule fungicide time spray for controlling leaf rust progress in wheat fields.
      Experiments including a single fungicide treatment based upon the DSS along with
      double and triple treatment were carried out over the 2007-2009 cropping seasons
      in four representative Luxembourgish wheat field locations. The study showed that
      the WLR occurrences and severities differed according to the site, cultivar, and
      year. We also found out that the single fungicide treatment based on the DSS
      allowed a good protection of the three upper leaves of susceptible cultivars in
      fields with predominant WLR occurrences. The harvested grain yield was not
      significantly different from that of the double and triple fungicide-treated
      plots (P < 0.05). Such results could serve as basis or be coupled to cost
      effective and environmentally friendly crop management systems in operational
      context.

PMID- 24464137
TI  - Laminar and intermittent flow in a tilted heat pipe.
AB  - Heat transfer measurements performed by Riedinger et al. (Phys. Fluids, 25,
      015117 (2013)) showed that in an inclined channel, heated from below and cooled
      from above with adiabatic walls, the flow is laminar or intermittent (local
      bursts can occur in the laminar flow) when the inclination angle is sufficiently
      high and the applied power sufficiently low. In this case, gravity plays a
      crucial role in the characteristics of the flow. In this paper, we present
      velocity measurements, and their derived tensors, obtained with Particle Image
      Velocimetry inside the channel. We, also, propose a model derived from a jet
      interpretation of the flow. Comparison between experiment and model shows a fair
      agreement. 

PMID- 24464138
TI  - Promote potential applications of nanoparticles as respiratory drug carrier:
      insights from molecular dynamics simulations.
AB  - Nanoparticles (NPs) show great promises in biomedical applications as the
      respiratory drug carrier system. Once reaching the alveolar region, NPs first
      interact with the pulmonary surfactant (PS) film, which serves as the first
      biological barrier and plays an important role in maintaining the normal
      respiratory mechanics. Therefore, understanding the interactions between NPs and
      PS can help promote the NP-based respiratory drug carrier systems. Using coarse
      grained molecular dynamics simulations, we studied the effect of rigid spherical
      NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine
      (DPPC) monolayer at the air-water interface. Four different NPs were considered,
      including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5
      nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers,
      which have been widely used for nanoscale drug carrier systems). Our simulations
      showed that hydrophilic NPs can readily penetrate into the aqueous phase with
      little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to
      induce large structural disruptions, thus inhibiting the normal phase transition
      of the DPPC monolayer upon film compression. Our simulations also showed that
      this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation.
      Our results provide useful guidelines for molecular design of NPs as carrier
      systems for pulmonary drug delivery. 

PMID- 24464139
TI  - Skin and soft tissue infections caused by nontuberculous mycobacteria.
AB  - PURPOSE OF REVIEW: Skin and soft tissues infections (SSTIs) caused by
      nontuberculous mycobacteria (NTM) are underrecognized and difficult to treat.
      Controversies exist for optimal medical management and the role of surgery.
      Defining the epidemiology in the environment, in animals and in healthcare aids
      disease prevention. This review focuses on recent advances in epidemiology, risk
      factors, diagnostics and therapy. RECENT FINDINGS: The increasing consumer
      appetite for cosmetic and body-modifying procedures (e.g. tattooing, mesotherapy,
      liposuction) has been associated with rises in sporadic cases and outbreaks of
      NTM SSTIs. In mainstream healthcare, recent epidemiological studies have helped
      to quantify the increased risk of NTM infection related to anti-tumour necrosis
      factor-alpha monoclonal antibody therapy. Cervicofacial lymphadenitis in children
      poses management dilemmas, but recent studies and resultant algorithms have
      simplified decision-making. Molecular studies have led to a better understanding
      of the epidemiology, therapy and course of Mycobacterium ulcerans infection
      (Buruli ulcer) that remains prevalent in many areas including sub-Saharan Africa
      and southeastern Australia. Apart from molecular methods, the widespread adoption
      of matrix-assisted laser desorption ionization-time of flight mass spectrometry
      by routine laboratories has potential to simplify and expedite the laboratory
      identification of NTMs. SUMMARY: An improved understanding of the epidemiology of
      NTM SSTIs indicates a need to apply effective infection control and ensure
      regulation of cosmetic and related procedures associated with nonsterile fluids.
      Broader access to newer diagnostic methods will continue to improve recognition
      of NTM disease. Along with a paucity of therapeutic agents, there is need for
      more reliable methods to assess susceptibility and selection of effective
      combination therapy.

PMID- 24464140
TI  - Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor
      cells in patients with GvHD.
AB  - Extracorporeal photopheresis (ECP) is beneficial in patients with T-cell-mediated
      disorders, including GvHD, but the underlying immunological mechanisms are
      incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate
      immune cells characterized by their capacity to suppress T-cell proliferation. We
      quantified MDSCs by flow cytometry in peripheral blood from patients after BMT
      with GvHD before and after ECP treatment, patients after BMT but without GvHD and
      age-matched healthy controls. MDSC functionality was analyzed using T-cell
      proliferation, cytokine release and arginase activity. GvHD patients showed
      increased baseline percentages of neutrophilic MDSCs (PMN-MDSCs) compared with
      healthy controls and patients after BMT without GvHD. ECP treatment in GvHD
      patients rapidly increased circulating percentages of PMN-MDSCs. Functionally,
      PMN-MDSCs efficiently dampened Th1 and Th17 responses and were paralleled by an
      increase of cellular and extracellular arginase activity. Following ECP
      longitudinally over 16 weeks, two GvHD responder subgroups were identified, with
      group one continuously increasing PMN-MDSCs and group two with stable or
      decreasing PMN-MDSCs over time. This study demonstrates for the first time that
      ECP increases T-cell-dampening PMN-MDSCs in GvHD patients, a finding that should
      be confirmed in larger series of GvHD patients. 

PMID- 24464141
TI  - Stromal cells-are they really useful for GVHD?
AB  - Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are
      increasingly being used for the treatment of acute and chronic GVHD. Although
      they seem immuno-privileged, they induce alloresponses, but the risk of
      immunization is poorly characterized. After infusion, they first reach the lungs,
      liver and spleen, and are then difficult to trace. Several mechanisms are
      involved in stromal cells suppressing alloreactivity, such as induction of
      regulatory T cells, but whether or not this will also affect leukemic relapse or
      increase infections is not known. Although several encouraging pilot studies have
      been published, there have been few prospective randomized trials. There may be a
      bias in the literature, as negative results are seldom published, and there have
      been few comparative studies with other immunosuppressive regimens. Most animal
      models have failed to show any effect on GVHD. Several questions remain to be
      answered for optimization of stromal cell therapy. Which source is optimal-BM,
      fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture
      conditions are most appropriate and at what passage and how frequently should
      cells be administered? More research is required to move stromal cell therapy
      forward to become an established treatment for acute and chronic GVHD. 

PMID- 24464142
TI  - Investigator feedback about the 2005 NIH diagnostic and scoring criteria for
      chronic GVHD.
AB  - The 2005 National Institutes of Health (NIH) consensus criteria for chronic GVHD
      have set standards for reporting. Many questions, however, have arisen regarding
      their implementation and utilization. To identify perceived areas of controversy,
      we conducted an international survey on diagnosis and scoring of chronic GVHD.
      Agreement was observed for 50-83% of the 72 questions in 7 topic areas. There was
      agreement on the need for modifying criteria in six situations: two or more
      distinctive manifestations should be enough to diagnose chronic GVHD; symptoms
      that are not due to chronic GVHD should be scored differently; active disease and
      fixed deficits should be distinguished; a minimum threshold body surface area of
      hidebound skin involvement should be required for a skin score of 3; asymptomatic
      oral lichenoid changes should be considered a score 1; and lung biopsy should be
      unnecessary to diagnose chronic GVHD in a patient with bronchiolitis obliterans
      as the only manifestation. The survey also identified 26 points of controversy.
      Whenever possible, studies should be conducted to confirm the appropriateness of
      any revisions. In cases where data are not available, clarification of the NIH
      recommendations by consensus is necessary. This survey should inform future
      research in the field and revisions of the current consensus criteria. 

PMID- 24464143
TI  - Fludarabine metabolite level on day zero does not affect outcomes of
      hematopoietic cell transplantation in patients with normal renal function.

PMID- 24464144
TI  - A review of the haematopoietic stem cell donation experience: is there room for
      improvement?
AB  - Donation of haematopoietic stem cells, either through BM or PBSC collection, is a
      generally safe procedure for healthy donors although adverse reactions are a
      definite risk. The invaluable source of donation and its central role in
      transplantation implies that every effort should be made to alleviate possible
      difficulties the donor encounters. The physical and psychological reactions to
      donation have been established for some time, but less is known about the factors
      that are associated with a poorer donation experience. In this article, we
      provide an overview of the physical and psychological donation experience and
      focus attention on demographic, physical and psychological factors that may
      influence this donation experience. Understanding that toxicity profiles vary
      with certain donor characteristics is crucial as this knowledge could influence
      practice in numerous ways including the modification of joining and recruitment
      policies and the improvement of supportive measures and donor follow-up
      procedures. Although this review deals with both unrelated and related donors
      (RDs), there is a relative paucity of regulation of RD care and we call for more
      attention to this area. Owing to the relative rarity of donation in each country,
      a global effort to collect donor outcome data is needed. 

PMID- 24464146
TI  - Genetic insight into the pathogenesis of nonalcoholic fatty liver disease.

PMID- 24464145
TI  - Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell
      depletion for adult severe aplastic anemia after modified conditioning and
      supportive therapy.
AB  - HLA-haploidentical hematopoietic SCT (HSCT) is an option for severe aplastic
      anemia (SAA) patients. Here, we evaluated the outcomes of 26 adult-SAA patients
      who received HLA-haploidentical HSCT in five transplant centers in southwestern
      China. Most of the patients in this study failed prior therapy and were
      transfused heavily before the transplantation. The patients received
      fludarabine+cyclophosphamide+antithymocyte globulin as conditioning regimens and
      then unmanipulated peripheral blood plus marrow transplantation. Micafungin, i.v.
      Ig and recombinant human TPO were used for post-grafting infection prevention and
      supportive care. Of 26 patients, 25 achieved engraftment at a median of 13 days
      (range, 11-19 days) after HSCT. One of 25 patients experienced graft rejection
      and did not achieve sustained engraftment after second HSCT. Therefore, the final
      engraftment rate was 92.3%. Three of 25 (12%) patients developed acute GVHD, 10
      of 25 (40%) patients developed chronic GVHD (9 with limited whereas the other
      with extensive). The OS rate was 84.6% and the average follow-up time was 1313.2
      (738-2005) days for surviving patients. This encouraging result suggests that HLA
      haploidentical HSCT is an effective therapeutic option for adults with acquired
      SAA if an HLA-identical donor is not available. 

PMID- 24464147
TI  - Quest for Life on MARS: mission incomplete.

PMID- 24464148
TI  - Changes in prescription patterns of acid-suppressant medications by Belgian
      pediatricians: analysis of the national database, [1997-2009].
AB  - OBJECTIVE: The aim of this study was to examine the trend in the prescribing of
      proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H2-RAs) for
      children in Belgium from 1997 to 2009 to encourage discussion regarding
      appropriate clinical use. METHODS: Monthly claim-based data for PPIs and H2-RAs
      were obtained from the national health insurance database (Pharmanet 1997-2009).
      RESULTS: The total monthly volume of all reimbursed antireflux medications,
      prescribed by Belgian pediatricians, increased 7-fold from 20,782 daily defined
      doses (DDDs) in January 1997 to 142,912 DDDs in June 2009. During this study
      period, reimbursed volume of H2-RAs increased from 2575 to 38,996 DDDs and of
      PPIs from 3472 to 103,926 DDDs per month. CONCLUSIONS: PPI use has increased
      substantially in children. Its use does not seem to be commensurate with the
      prevalence of gastroesophageal reflux disease in children. This study encourages
      clinical discussion regarding well-considered use of these drugs in children.

PMID- 24464149
TI  - Esophageal polyps in children.

PMID- 24464150
TI  - Sirolimus, a promising treatment for refractory Kaposiform hemangioendothelioma.
AB  - BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a locally aggressive
      vascular tumor that usually occurs in infants. It is commonly associated with
      Kasabach-Merritt phenomenon which is directly responsible for the significant
      morbidity and mortality, including hemodynamic instability, local invasion, and
      compression of vital structures. Treatment is particularly difficult for those
      who had no response to conventional therapies. This paper wants to share
      experience of mTOR inhibitors sirolimus in the treatment of refractory KHE.
      MATERIALS AND METHODS: Six cases of refractory KHE were diagnosed and treated in
      Children's Hospital of Fudan University from Jan 2010-June 2013; all of them were
      treated with sirolimus in June 2012 after failing multiple other therapies.
      RESULTS: In six patients, gender was equally distributed between male and female
      patients. The mean age at the time of initial diagnosed as KHE was 3.1 +/- 1.8
      months. All of them had been pretreated with at least 2 medical therapies. All of
      them showed significant improvement in clinical status with tolerable side
      effects. The average time to response was 5.3 +/- 1.0 days; the average
      stabilization time of platelet was 15.1 +/- 8.0 days; and the average time for
      sirolimus treated as single agent was 1.7 +/- 0.4 months. No recurrence of their
      symptoms happened. CONCLUSIONS: Sirolimus appears to be effective and safe in
      patients with life-threatening KHE and represents a promising tool in treating
      refractory KHE.

PMID- 24464151
TI  - Serum potassium is an age-dependent risk factor for pre-diabetes and diabetes in
      the Israeli population.
AB  - OBJECTIVE: We analysed the association between serum potassium, within the normal
      range, and early signs of diabetes in an Israeli population. RESEARCH DESIGN AND
      METHODS: A computerized database of the Clalit Health Services was used for
      obtaining information regarding patients' baseline serum potassium levels. The
      main study outcome was dysglycaemia, defined as fasting glucose > 100 mg/dL,
      HbA1C > 6.5 gr% (48 mmol/mol) or a new diagnosis of diabetes. A secondary outcome
      was overt diabetes. RESULTS: Included in the study were 71,597 patients, mean age
      40.8 +/- 13.4 years. After a mean follow-up period of 5.3 +/- 2.2 years,
      dysglycaemia decreased [odds ratio (OR) = 0.95; 95% confidence interval (CI) =
      0.906-0.997; p = 0.038], as did the incidence of overt diabetes (OR = 0.86; 95%
      CI = 0.793-0.934; p = 0.0001), for every 1 mmol/L elevation in serum potassium in
      the normal range. But analysis of subpopulation reveals that when elevated serum
      potassium was associated with low adjusted ORs for predicting dysglycaemia (OR =
      0.904 with a 95% CI of 0.849-0.963; p = 0.002), the opposite effect was
      demonstrated over the age of 41 years (OR = 1.113 with a 95% CI of 1.048-1.104; p
      < 0.001). CONCLUSIONS: This study demonstrates age-related association between
      serum potassium and the risk of dysglycaemia.

PMID- 24464152
TI  - Neural and behavioural responses to face-likeness of objects in adolescents with
      autism spectrum disorder.
AB  - Numerous studies have revealed atypical face processing in autism spectrum
      disorders (ASD) characterized by social interaction and communication
      difficulties. This study investigated sensitivity to face-likeness in ASD. In
      Experiment 1, we found a strong positive correlation between the face-likeness
      ratings of non-face objects in the ASD (11-19 years old) and the typically
      developing (TD) group (9-21 years old). In Experiment 2 (the scalp-recorded event
      related potential experiment), the participants of both groups (ASD, 12-19 years
      old; TD, 12-18 years old) exhibited an enhanced face-sensitive N170 amplitude to
      a face-like object. Whereas the TD adolescents showed an enhanced N170 during the
      face-likeness judgements, adolescents with ASD did not. Thus, both individuals
      with ASD and TD individuals have a perceptual and neural sensitivity to face-like
      features in objects. When required to process face-like features, a face-related
      brain system reacts more strongly in TD individuals but not in individuals with
      ASD. 

PMID- 24464153
TI  - SLE and dental erosion: a lethal cocktail.
AB  - A 13-year-old Pacific Island girl presented complaining of fever, joint pain and
      dry mouth. She was using limes to relieve her dry mouth. On examination, the most
      striking clinical finding was severe dental erosion and caries. Autoimmune
      serology confirmed a diagnosis of systemic lupus erythematosus (SLE) with
      possible Sjogren's syndrome. The case illustrates the devastating consequence of
      excessive consumption of acidic citrus juice in sicca syndrome. 

PMID- 24464154
TI  - [Not Available].

PMID- 24464155
TI  - [The diseases of the soul in medieval arabic texts an encounter between
      philosophy and medicine].
AB  - In the medical texts written in Arabic between the 9(th) and the 11(th)
      centuries, the diseases of the soul played an important part in the physicians'
      reflection on the nature of the soul and its relationship to the body. In the
      9(th) and the beginning of the 10(th) century, this medical anthropology was
      shaped by a tradition that was both Platonic and Galenic. But in the 10(th), the
      influence of Aristotle became most prominent in Arabic philosophy, and as a
      result the main lines of this medical anthropology were questioned, as was the
      role of medical knowledge and its relation to natural philosophy. 

PMID- 24464156
TI  - [The medical reconstruction of human nature in the 11(th) and 12 (th) centuries].
AB  - At the end of the 11(th) century, translations of Greek and above all Arabic
      texts played an important role in the building of a new medical science in
      western christendom. Although the men reading these texts were not all
      physicians, they could find in them a representation of human nature showing both
      its specificities and its similarities with the inanimate world. This
      representation, which was circulating before philosophical texts were first
      translated, emphasized the links between the state of the body and the passions
      of the soul, without assuming a psychological determinism that would have been
      unacceptable in the Christian context. 

PMID- 24464157
TI  - [Human nature and the complexion of the body as seen by Italian physicians at the
      end of the middle ages].
AB  - Is it possible to apprehend man from a medical standpoint without offering a
      purely materialistic definition ? Such was the question raised by Italian
      physicians at the end of the Middle Ages when they developed a full scale theory
      of the idea of complexion, which they saw as a "substantial quality" specific to
      man, but one that also depended on hereditary traits, food, age, or even climate
      and mores. Practicing their art, some of these physicians could thus contemplate
      improving not simply the health, but also the well being of each individual. 

PMID- 24464158
TI  - [Medical practice and the discourse on man in the early modern period].
AB  - In the 16(th) and 17(th) centuries, medical knowledge was anthropological in so
      much as it produced a discourse on man whose ambition and legitimacy needed no
      justification. Underwritten by the belief that the body was an object of science,
      the epistemic horizons of a doctrina de homine emerged from the interaction of
      medical practice, particularly anatomy, with philosophy and theology in a
      specific framework - the reorganization of knowledge in Europe over the "long
      16(th) century". 

PMID- 24464159
TI  - [Not Available].

PMID- 24464160
TI  - [Not Available].

PMID- 24464161
TI  - Variations in daylight as a contextual cue for estimating season, time of day,
      and weather conditions.
AB  - Experience and experiments on human color constancy (i.e., Arend & Reeves, 1986;
      Craven & Foster, 1992) tell us that we are capable of judging the illumination.
      However, when asked to make a match of the illuminant's color and brightness,
      human observers seem to be quite poor (Granzier, Brenner, & Smeets, 2009a). Here
      we investigate whether human observers use (rather than match) daylight for
      estimating ecologically important dimensions: time of year, time of day, and
      outdoor temperature. In the first three experiments we had our observers evaluate
      calibrated color images of an outdoor urban scene acquired throughout a year.
      Although some observers could estimate the month and the temperature, overall
      they were quite poor at judging the time of day. In particular, observers were
      not able to discriminate between morning and afternoon pictures even when they
      were allowed to compare multiple images captured on the same day (Experiment 3).
      However, observers could distinguish between midday and sunset and sunrise
      daylight. Classification analysis showed that, given a perfect knowledge of its
      variation, an ideal observer could have performed the task over chance only
      considering the average chromatic variation in the picture. Instead, our
      observers reported using shadows to detect the position of the sun in order to
      estimate the time of day. However, this information is highly unreliable without
      knowledge of the orientation of the scene. In Experiment 4 we used an LED chamber
      in order to present our observers with lights whose chromaticity and illuminance
      varied along the daylight locus, thus isolating the light cues from the sun
      position cue. We conclude that discriminating the slight variations in
      chromaticity and brightness, which potentially distinguish morning and afternoon
      illuminations, lies beyond the ability of human observers.

PMID- 24464162
TI  - Interocular transfer of perceptual skills after sleep.
AB  - Several studies suggest that sleep improves perceptual skills in the visual
      texture discrimination task (TDT). Here we report that besides consolidation,
      sleep also generalizes the learned perceptual abilities to the untrained eye.
      Healthy volunteers (n = 32) were trained on the TDT, in which they had to
      discriminate between horizontal and vertical target textures briefly presented in
      the periphery of the visual field (left upper quadrant). After a 10-hr interval
      filled with either sleep or wakefulness, they were retested first on the trained
      eye in the trained quadrant and then on the untrained eye and quadrant. In line
      with prior findings, visual discrimination was globally higher after sleep than
      after wakefulness, as compared to performance levels at the end of training.
      Furthermore, discrimination performance was significantly improved only in the
      sleep condition for the untrained eye in the same quadrant, but also showed a
      trend to generalize to the untrained eye and untrained quadrant. Our results
      suggest that sleep-dependent perceptual skills continue developing at a later
      visual-process stage than the V1 area, where learning is not monocular anymore. 

PMID- 24464163
TI  - The effect of photometric and geometric context on photometric and geometric
      lightness effects.
AB  - We measured the lightness of probe tabs embedded at different orientations in
      various contextual images presented on a computer-controlled stereo display. Two
      background context planes met along a horizontal roof-like ridge. Each plane was
      a graphic rendering of a set of achromatic surfaces with the simulated
      illumination for each plane controlled independently. Photometric context was
      varied by changing the difference in simulated illumination intensity between the
      two background planes. Geometric context was varied by changing the angle between
      them. We parsed the data into separate photometric effects and geometric effects.
      For fixed geometry, varying photometric context led to linear changes in both the
      photometric and geometric effects. Varying geometric context did not produce a
      statistically reliable change in either the photometric or geometric effects. 

PMID- 24464164
TI  - The achromatic locus: effect of navigation direction in color space.
AB  - An achromatic stimulus is defined as a patch of light that is devoid of any hue.
      This is usually achieved by asking observers to adjust the stimulus such that it
      looks neither red nor green and at the same time neither yellow nor blue. Despite
      the theoretical and practical importance of the achromatic locus, little is known
      about the variability in these settings. The main purpose of the current study
      was to evaluate whether achromatic settings were dependent on the task of the
      observers, namely the navigation direction in color space. Observers could either
      adjust the test patch along the two chromatic axes in the CIE u*v* diagram or,
      alternatively, navigate along the unique-hue lines. Our main result is that the
      navigation method affects the reliability of these achromatic settings. Observers
      are able to make more reliable achromatic settings when adjusting the test patch
      along the directions defined by the four unique hues as opposed to navigating
      along the main axes in the commonly used CIE u*v* chromaticity plane. This result
      holds across different ambient viewing conditions (Dark, Daylight, Cool White
      Fluorescent) and different test luminance levels (5, 20, and 50 cd/m(2)). The
      reduced variability in the achromatic settings is consistent with the idea that
      internal color representations are more aligned with the unique-hue lines than
      the u* and v* axes. 

PMID- 24464165
TI  - Exploring V1 by modeling the perceptual quality of images.
AB  - We propose an image quality model based on phase and amplitude differences
      between a reference and a distorted image. The proposed model is motivated by the
      fact that polar representations can separate visual information in a more
      independent and efficient manner than Cartesian representations in the primary
      visual cortex (V1). We subsequently estimate the model parameters from a large
      subjective data set using maximum likelihood methods. By comparing the various
      model hypotheses on the functional form about the phase and amplitude, we find
      that: (a) discrimination of visual orientation is important for quality
      assessment and yet a coarse level of such discrimination seems sufficient; and
      (b) a product-based amplitude-phase combination before pooling is effective,
      suggesting an interesting viewpoint about the functional structure of the simple
      cells and complex cells in V1. 

PMID- 24464166
TI  - The challenges of providing quality palliative care to all.
AB  - Welcome to the 20th volume of the International Journal of Palliative Nursing,
      marking 19 years of the journal. We have in so many respects come such a long way
      in palliative nursing since that first issue. Notable changes include the marked
      proliferation of palliative care around the world, advances in pain and symptom
      control, improvements in nursing roles, refinements of the definition and scope
      of palliative care, and growth in the number of education courses and their
      methods and means of delivery. 

PMID- 24464167
TI  - Breakthrough cancer pain: the current situation.
AB  - Breakthrough pain is common in patients with cancer. This paper describes the
      clinical features of breakthrough cancer pain (BTcP) and its impact on activities
      of daily living. It also describes the principles of BTcP management,
      highlighting some of the current issues and problems. A follow-up paper will
      describe current approaches to managing BTcP. 

PMID- 24464168
TI  - Clinical nurse specialists perspectives on advance care planning conversations: a
      qualitative study.
AB  - OBJECTIVE: The aim of the study was to identify the challenges experienced by
      clinical nurse specialists (CNSs) when facilitating advance care planning (ACP)
      conversations with terminally ill patients. This paper focuses on the factors
      that influence CNSs when they are deciding whether to open an ACP discussion.
      METHODS: Semi-structured interviews were used to collect data from eight
      purposively selected palliative care CNSs working in two different community
      teams. The interviews were recorded, transcribed, and analysed to identify
      themes. FINDINGS: ACP required the CNSs to 'walk a tightrope', balancing
      potential harm with purported benefit. The nurses identified that their decision
      to introduce an ACP discussion was influenced by three key factors: an assessment
      of the patient's readiness to discuss the topic, their physical condition, and
      the nurse's relationship with the patient and family. CONCLUSION: ACP involves
      risk-taking on the part of those initiating it, owing to the potential for
      unforeseen or negative consequences. Further research is required to identify the
      factors that facilitate nurses involving patients in ACP.

PMID- 24464169
TI  - The development of the Grip on Challenging Behaviour dementia care programme.
AB  - BACKGROUND: Current guidelines and theories on the origin of challenging
      behaviour in dementia indicate that a structured multidisciplinary approach to
      its management is necessary. In the Grip on Challenging Behaviour study, a care
      programme was developed to improve the management of challenging behaviour.
      METHOD: In developing the care programme, the overlapping parts of dementia care
      guidelines were supplemented with discipline-specific parts. Three meetings with
      experts were arranged to further develop the structure of the care programme and
      to ensure a good fit with practice. RESULTS: The care programme consists of four
      steps: detection, analysis, treatment, and evaluation. For each step, forms were
      developed to guide and structure the process and assign responsibilities for each
      discipline. As well as a description of the development and the content of the
      care programme, this paper presents two case studies in which the programme was
      used. CONCLUSION: The Grip on Challenging Behaviour care programme provides a way
      for dementia special care units to manage challenging behaviour in a structured
      way and with a multidisciplinary approach making use of their own resources.

PMID- 24464170
TI  - An evaluation of routine specialist palliative care for patients on the Liverpool
      Care Pathway.
AB  - INTRODUCTION: This report describes a service evaluation of the 'added value' of
      routine specialist palliative care team (SPCT) involvement with patients on the
      Liverpool Care Pathway for the Dying Patient (LCP). METHODS: In the authors'
      hospital, patients that are commenced on the LCP are routinely referred to the
      SPCT. They are reviewed on the day of referral and then at least every other day,
      depending on the clinical situation. The data for this report was obtained by
      reviewing the SPCT's clinical database and the patients' LCP proformas. RESULTS:
      The SPCT intervened in the care of 80% of 158 newly referred patients, e.g. for
      alteration of continuous subcutaneous infusion (23%) or alteration of use of non
      pharmacological interventions (21%). Furthermore, 11% of patients were taken off
      the LCP, around one quarter of whom were later put back on. CONCLUSIONS: The
      authors' model of care could overcome many of the issues relating to the LCP and
      would ameliorate the developing vacuum of care for patients at the end of life.

PMID- 24464171
TI  - Three approaches to delivering end-of-life education to care homes in a region of
      south east England.
AB  - There has been considerable investment in end-of-life care education for the care
      home sector in recent years. This article looks at three recent initiatives in
      West Sussex in south east England and appraises the advantages and disadvantages
      of each. The three initiatives were an action learning project, a Six Steps to
      Success care home programme, and a Gold Standards Framework for Care Home
      programme. The details of how each approach was operationalised and the initial
      results and evaluations are discussed. It is essential that end-of-life educators
      working in the same geographical area communicate and build on one another's
      contributions, and this article is an instance of such collaboration. 

PMID- 24464172
TI  - Challenges UK paramedics currently face in providing fully effective end-of-life
      care.
AB  - Paramedics play an integral part in community end-of-life care (EoLC) in the UK,
      especially given the lack of out-of-hours cover by palliative care specialists.
      Despite this, there remain multiple barriers to their fully effective provision
      of such care. This article provides a brief historical overview of paramedic
      practice, before highlighting some of the barriers to effective paramedic EoLC
      provision and introducing examples of collaborative work in the UK that aim to
      overcome these. The author hopes this will support improvements in paramedic-led
      EoLC. Given the similarities in the international evolution of paramedic
      education, readers from other countries will be able to relate to these findings.

PMID- 24464173
TI  - When the saints go marching on.
AB  - Having worked as a specialty doctor in palliative care for the past 6 years and
      now returning to general practice, I have become increasingly uncertain as to the
      future role of in-patient hospices. Perhaps the time has come for a realistic
      look at where exactly they fit in to the bigger picture of end-of-life care. Of
      particular concern is whether their existence inhibits the development of other
      services and fuels the myth that palliative care is different from simply good
      care. 

PMID- 24464176
TI  - Plasma phospholipids indicate impaired fatty acid homeostasis in preterm infants.
AB  - BACKGROUND: During fetal development, docosahexaenoic (DHA) and arachidonic acid
      (ARA) are particularly enriched in brain phospholipids. After preterm delivery,
      fetal enrichment of DHA and ARA via placental transfer is replaced by enteral and
      parenteral nutrition, which is rich in linoleic acid (LA) instead. Specific DHA
      and ARA enrichment of lipoproteins is reflected by plasma phosphatidylcholine
      (PC) species, whereas plasma phosphatidylethanolamine (PE) composition reflects
      hepatic stores. OBJECTIVE: We profiled PC and PE species in preterm infant
      plasma, compared with cord and maternal blood, to assess whether current feeding
      practice meets fetal conditions in these patients. DESIGN: Preterm infant plasma
      (N = 171, 23-35 w postmenstrual age (PMA), postnatal day 1-103), cord plasma (N =
      194) and maternal serum (N = 121) (both 24-41 w PMA) were collected. After lipid
      extraction, PC and PE molecular species were analyzed using tandem mass
      spectrometry. RESULTS: Phospholipid concentrations were higher in preterm infant
      than in cord plasma after correction for PMA. This was mainly due to postnatal
      increases in LA-containing PC and PE, resulting in decreased fractions of their
      DHA- and ARA-containing counterparts. These changes in preterm infant plasma
      phospholipids occurred during the time of transition to full enteral feeds (day 0
      10 after delivery). Thereafter, the fraction of ARA-containing phospholipids
      further decreased, whereas that of DHA slowly reincreased but remained at a level
      50% of that of PMA-matched cord blood. CONCLUSIONS: The postnatal increase in LA
      PC in preterm infant plasma results in decreased fractions of DHA-PC and ARA-PC.
      These changes are also reflected by PE molecular composition as an indicator of
      altered hepatic fatty acid homeostasis. They are presumably caused by
      inadequately high LA, and low ARA and DHA supply, at a stage of development when
      ARA-PC and DHA-PC should be high, probably reducing the availability of DHA and
      ARA to the developing brain and contributing to impaired neurodevelopment of
      preterm infants.

PMID- 24464177
TI  - Evaluation of current approaches to stream classification and a heuristic guide
      to developing classifications of integrated aquatic networks.
AB  - Conservation and management of fresh flowing waters involves evaluating and
      managing effects of cumulative impacts on the aquatic environment from
      disturbances such as: land use change, point and nonpoint source pollution, the
      creation of dams and reservoirs, mining, and fishing. To assess effects of these
      changes on associated biotic communities it is necessary to monitor and report on
      the status of lotic ecosystems. A variety of stream classification methods are
      available to assist with these tasks, and such methods attempt to provide a
      systematic approach to modeling and understanding complex aquatic systems at
      various spatial and temporal scales. Of the vast number of approaches that exist,
      it is useful to group them into three main types. The first involves modeling
      longitudinal species turnover patterns within large drainage basins and relating
      these patterns to environmental predictors collected at reach and upstream
      catchment scales; the second uses regionalized hierarchical classification to
      create multi-scale, spatially homogenous aquatic ecoregions by grouping adjacent
      catchments together based on environmental similarities; and the third approach
      groups sites together on the basis of similarities in their environmental
      conditions both within and between catchments, independent of their geographic
      location. We review the literature with a focus on more recent classifications to
      examine the strengths and weaknesses of the different approaches. We identify
      gaps or problems with the current approaches, and we propose an eight-step
      heuristic process that may assist with development of more flexible and
      integrated aquatic classifications based on the current understanding, network
      thinking, and theoretical underpinnings. 

PMID- 24464178
TI  - Fatty acid droplet self-division driven by a chemical reaction.
AB  - Division of a millimeter-sized and compartmentalized fatty acid droplet is
      triggered by a chemical pH clock reaction operating on the ten-second time scale.
      The autonomous pH change inside the compartment translates into the deprotonation
      of the fatty acid molecules, leading to a negative interfacial tension at the
      water-oil interface inside the droplet. This phenomenon induces the expansion of
      the droplet, which is followed by its division into daughter droplets governed by
      the Plateau-Rayleigh instability. 

PMID- 24464179
TI  - The Role of Lean Process Improvement in Implementation of Evidence-Based
      Practices in Behavioral Health Care.
AB  - To effectively implement evidence-based practices (EBP) in behavioral health
      care, an organization needs to have operating structures and processes that can
      address core EBP implementation factors and stages. Lean, a widely used quality
      improvement process, can potentially address the factors crucial to successful
      implementation of EBP. This article provides an overview of Lean and the
      relationship between Lean process improvement steps, and EBP implementation
      models. Examples of how Lean process improvement methodologies can be used to
      help plan and carry out implementation of EBP in mental health delivery systems
      are presented along with limitations and recommendations for future research and
      clinical application. 

PMID- 24464180
TI  - Racial/Ethnic Differences in the Relationship between Obesity and Depression
      Treatment.
AB  - Using data from the 2004 to 2008 Medical Expenditure Panel Survey (MEPS), this
      study examined the relationship between obesity and the treatment of depression
      across racial/ethnic subgroups, controlling for depressive symptoms, self-rated
      mental health, health status, and socioeconomic characteristics. The association
      between obesity and depression-related medication was significant for white women
      but not for black or Hispanic women. Similarly, the association between obesity
      and depression-related ambulatory visits was significant for white women but not
      for black or Hispanic women. The results for men were, in general, mixed and
      inconsistent. The significant racial/ethnic differences found in the relationship
      between obesity and depression treatment among women suggest that social and
      cultural factors might play important roles in depression treatment among women. 

PMID- 24464181
TI  - IL-15 receptor alpha rs2228059 A>C polymorphism was associated with a decreased
      risk of esophageal cancer in a Chinese population.
AB  - Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide.
      Esophageal cancer is very aggressive; genetic polymorphisms may explain in part
      the individual differences in esophageal cancer susceptibility. We conducted a
      hospital based case-control study to evaluate the genetic effects of functional
      single nucleotide polymorphisms (SNPs) in the interleukin (IL)-15 and IL-15
      receptor alpha (IL-15RA) gene on the development of esophageal cancer. A total of
      380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were
      recruited for this study. The genotypes were determined using a custom-by-design
      48-Plex SNPscan(TM) kit. The IL-15RA rs2228059 A>C polymorphism was associated
      with a decreased risk of ESCC in a recessive genetic model; However, there was no
      significant association between the other five SNPs and ESCC risk. Stratified
      analyses indicated a significantly decreased risk of ESCC associated with the IL
      15RA rs2228059 A>C polymorphism was evident among male, older, non-smoker, and
      non-drinker patients. These findings indicated that the functional polymorphism,
      IL-15RA rs2228059 A>C, might contribute to ESCC susceptibility. However, the
      statistical power of our study was limited because of the moderate sample size
      and absence of a validation cohort. Large well-designed studies are warranted to
      confirm our findings.

PMID- 24464182
TI  - Caspase8 rs1035142 G>T polymorphism was associated with an increased risk of
      esophageal cancer in a Chinese population.
AB  - Esophageal cancer is one of the ten most common cancers in the world and has poor
      prognosis. Apoptosis is considered a fundamental component in cancer
      pathogenesis. We conducted a hospital-based case-control study to evaluate the
      genetic effects of 16 apoptosis associated single nucleotide polymorphisms (SNPs)
      on esophageal cancer development. A total of 380 esophageal squamous cell
      carcinoma (ESCC) cases and 380 controls were recruited for this study. Genotypes
      were determined using a custom-by-design 48-Plex SNPscanTM Kit. The caspase8
      (CASP8) rs1035142 G>T polymorphism was associated with increased risk of ESCC by
      heterozygote comparison, homozygote comparison, a dominant genetic model and a
      recessive genetic model. However, no significant association was detected between
      the other 15 SNPs and ESCC risk. Stratified analyses indicated a significantly
      increased risk of ESCC associated with CASP8 rs1035142 G>T polymorphism was
      evident among all subgroups. These findings indicated that the functional
      polymorphism CASP8 rs1035142 G>T might contribute to ESCC susceptibility.

PMID- 24464183
TI  - The effects of p38 gene silencing on breast cancer cells.
AB  - p38 mitogen-activated protein kinases (MAPK) are members of the MAPK family that
      are activated by inflammatory cytokines and a variety of environmental stresses.
      It mediates various biological processes. p38 MAPK activity play important roles
      in tumour progression. Excessive p38 expression is observed in invasive breast
      cancers. The aim of the present study was to investigate whether the p38 siRNA
      transfection of breast cancer cells is a putative preventive treatment for human
      breast cancer. p38 siRNA was used at a concentration of 15, 30, and 100 nM in
      human breast cancer cell lines (MCF-7) and normal fibroblast cell lines (NIH
      3T3). After 48 and 72 h of transfection, the reduction in p38 expression was
      measured using quantitative real-time PCR. The activation of p38 signalling was
      measured by ELISA. XTT cell proliferation assay was performed to determine the
      effect of p38 silencing on MCF-7 and NIH 3T3 cell lines. The results demonstrated
      that approximately 96% gene silencing occurred by the selected siRNA targeting
      p38 mRNA. The most effective silencing was observed at 72 h post-transfection
      using 30 nM p38 siRNA. The results of ELISA showed that the expression of p38
      protein was inhibited by p38 siRNA at 30 nM siRNA and 100 nM at 72 h post
      transfection. XTT results showed that cells stimulated by 30 nM siRNA at 72 h
      post transfection were the lowest in proliferation. p38 siRNA can interfere with
      the expression of p38 at protein level in MCF-7 cells, result in inhibition of
      cell proliferation. p38 siRNA may be a critical regulator to promote the
      proliferation and protein expression in MCF-7 cells. In this study, we
      demonstrate that p38 silencing is a preventive maintenance for treating breast
      cancer.

PMID- 24464184
TI  - Interleukin-10-1082 gene polymorphism is associated with papillary thyroid
      cancer.
AB  - The etiopathogenesis of thyroid cancer has not been clearly elucidated although
      the role of chronical inflammation and the imbalance between pro- and anti
      inflammatory cytokines may play a role in the etiology. The aim of the present
      study was to investigate whether cytokine gene polymorphisms are associated with
      papillary thyroid cancer (PTC), and to evaluate the relationship between
      genotypes and clinical/laboratory manifestation of PTC. Tumor necrosis
      factoralpha (TNFalpha) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs
      1800795) and IL-10 A-1082G (rs 1800896) single nucleotide polymorphisms in DNA
      from peripheral blood leukocytes of 190 patients with thyroid cancer and 216
      healthy controls were investigated by real-time PCR combined with melting curve
      analysis. There was no notable risk for PTC afflicted by TNFalpha-308 and IL-6
      174 alone. However, IL-10-1082 G allele frequency were higher among PTC patients
      than healthy controls (p=0.009). The patients with IL-10-1082 GG geotype have
      twofold increased risk of developing thyroid cancer according to AA genotype (OR
      2.07, 95% CI 1.21-3.55). In addition, the concomitant presence of IL-10-1082 G
      allele (GG+AG genotypes) together with IL-6 -174 GG genotype has a nearly twofold
      increased risk for thyroid cancer (OR 1.75 with 95% CI 1.00-3.05, p=0.049). We
      suggest that IL-10-1082 G allele is associated with an increased risk of PTC. The
      polymorphism of IL-10 gene can improve our knowledge about the pathogenesis of
      PTC, and could provide to estimate people at the increased risk for PTC.

PMID- 24464185
TI  - Associations between C1431T and Pro12Ala variants of PPARgamma gene and their
      haplotypes with susceptibility to metabolic syndrome in an Iranian population.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone
      receptor that regulates a number of genes involved in lipid and carbohydrate
      metabolism. The aim of this study was to investigate the association of C1431T
      and Pro12Ala polymorphisms of PPARgamma gene and their haplotypes and diplotypes
      with risk of metabolic syndrome (MetS) in an Iranian population. A total of 340
      unrelated Iranian subjects, including 175 MetS patients and 165 normal controls
      were enrolled. Each group was then divided into two subgroups according to the
      genotype (Pro/Pro and Pro/Ala+Ala/Ala for Pro12Ala, CC and CT+TT for C1431T).
      Genotypes were determined using a TaqMan method. Anthropometric indices, fasting
      plasma glucose and fasting lipid profile were measured by routine methods. A
      significant difference in the frequencies of the C1431T genotypes was observed
      between MetS and control subjects (P=0.014), whereas no association was found for
      the Pro12Ala. The T allele carriers had a significantly increased risk of MetS
      compared to the CC genotype (P=0.016) even after correction for multiple-testing
      and adjustment for age, sex and genotype. The T allele may therefore be
      considered as a risk factor for MetS (P=0.003). Analysis of combined groups
      showed that X/Ala-CC and Pro/Pro-X/T diplotypes were associated with a higher
      body weight, waist circumference and waist to hip ratio among the individuals
      with MetS. Moreover the Ala-T haplotype was weakly associated with a higher level
      of triglyceride and lower level of HDL, suggesting the possibility of an
      interaction between Ala and T alleles. This study suggests that the PPARgamma
      C1431T polymorphism is related to an increased risk of MetS in an Iranian
      population and interacts with the Pro12Ala polymorphism, further increasing the
      risk of MetS.

PMID- 24464186
TI  - Spectinamides: a new class of semisynthetic antituberculosis agents that overcome
      native drug efflux.
AB  - Although the classical antibiotic spectinomycin is a potent bacterial protein
      synthesis inhibitor, poor antimycobacterial activity limits its clinical
      application for treating tuberculosis. Using structure-based design, we generated
      a new semisynthetic series of spectinomycin analogs with selective ribosomal
      inhibition and excellent narrow-spectrum antitubercular activity. In multiple
      murine infection models, these spectinamides were well tolerated, significantly
      reduced lung mycobacterial burden and increased survival. In vitro studies
      demonstrated a lack of cross resistance with existing tuberculosis therapeutics,
      activity against multidrug-resistant (MDR) and extensively drug-resistant
      tuberculosis and an excellent pharmacological profile. Key to their potent
      antitubercular properties was their structural modification to evade the Rv1258c
      efflux pump, which is upregulated in MDR strains and is implicated in macrophage
      induced drug tolerance. The antitubercular efficacy of spectinamides demonstrates
      that synthetic modifications to classical antibiotics can overcome the challenge
      of intrinsic efflux pump-mediated resistance and expands opportunities for target
      based tuberculosis drug discovery. 

PMID- 24464188
TI  - ADHD prevalence estimates across three decades: an updated systematic review and
      meta-regression analysis.
AB  - BACKGROUND: Previous studies have identified significant variability in attention
      deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely
      explained by methodological procedures. However, increasing rates of ADHD
      diagnosis and treatment throughout the past few decades have fuelled concerns
      about whether the true prevalence of the disorder has increased over time.
      METHODS: We updated the two most comprehensive systematic reviews on ADHD
      prevalence available in the literature. Meta-regression analyses were conducted
      to test the effect of year of study in the context of both methodological
      variables that determined variability in ADHD prevalence (diagnostic criteria,
      impairment criterion and source of information), and the geographical location of
      studies. RESULTS: We identified 154 original studies and included 135 in the
      multivariate analysis. Methodological procedures investigated were significantly
      associated with heterogeneity of studies. Geographical location and year of study
      were not associated with variability in ADHD prevalence estimates. CONCLUSIONS:
      Confirming previous findings, variability in ADHD prevalence estimates is mostly
      explained by methodological characteristics of the studies. In the past three
      decades, there has been no evidence to suggest an increase in the number of
      children in the community who meet criteria for ADHD when standardized diagnostic
      procedures are followed.

PMID- 24464189
TI  - Re: Sullivan SG, Greenland S. Bayesian regression in SAS software. Int J
      Epidemiol 2013;42:308-17.

PMID- 24464187
TI  - An abundant dysfunctional apolipoprotein A1 in human atheroma.
AB  - Recent studies have indicated that high-density lipoproteins (HDLs) and their
      major structural protein, apolipoprotein A1 (apoA1), recovered from human
      atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO).
      In vitro oxidation of either apoA1 or HDL particles by MPO impairs their
      cholesterol acceptor function. Here, using phage display affinity maturation, we
      developed a high-affinity monoclonal antibody that specifically recognizes both
      apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system. An oxindolyl
      alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope.
      Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated
      inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent
      cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2
      OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but
      accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1
      recovered from human atheroma or plasma is lipid poor, virtually devoid of
      cholesterol acceptor activity and demonstrated both a potent proinflammatory
      activity on endothelial cells and an impaired HDL biogenesis activity in vivo.
      Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n =
      627) were associated with increased cardiovascular disease risk. Circulating
      oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in
      the artery wall. 

PMID- 24464191
TI  - Commentary: Mediation and moderation analyses: a novel approach to exploring the
      complex pathways between maternal medical conditions, preterm birth and
      associated newborn morbidity risk.

PMID- 24464190
TI  - Effect of secular trends on age-related trajectories of cardiovascular risk
      factors: the Whitehall II longitudinal study 1985-2009.
AB  - BACKGROUND: Secular trends in cardiovascular risk factors have been described,
      but few studies have examined simultaneously the effects of both ageing and
      secular trends within the same cohort. METHODS: Development of cardiovascular
      risk factors over the past three decades was analysed using serial measurements
      from 10 308 participants aged from 35 to 80 years over 25 years of follow-up from
      five clinical examination phases of the Whitehall II study. Changes of body mass
      index, waist circumference, blood pressure and total and high-density lipoprotein
      cholesterol distribution characteristics were analysed with quantile regression
      models in the 57-61 age group. Age-related trajectories of risk factors were
      assessed by fitting mixed-effects models with adjustment for year of birth to
      reveal secular trends. RESULTS: Average body mass index and waist circumference
      increased faster with age in women than in men, but the unfavourable secular
      trend was more marked in men. Distributions showed a fattening of the right tail
      in each consecutive phase, meaning a stronger increase in higher percentiles.
      Despite the higher obesity levels in younger birth cohorts, total cholesterol
      decreased markedly in the 57-61 age group along the entire distribution rather
      than in higher extremes only. CONCLUSION: The past three decades brought strong
      and heterogeneous changes in cardiovascular risk factor distributions. Secular
      trends appear to modify age-related trajectories of cardiovascular risk factors,
      which may be a source of bias in longitudinal analyses.

PMID- 24464192
TI  - Are species' range limits simply niche limits writ large? A review of transplant
      experiments beyond the range.
AB  - Many species' range limits (RL) occur across continuous environmental gradients
      without obvious barriers imposing them. Such RL are expected to reflect niche
      limits (NL) and thus to occur where populations cease to be self-sustaining.
      Transplant experiments comparing fitness within and beyond species' ranges can
      test this hypothesis, but interpretive power depends strongly on experimental
      design. We first identify often overlooked aspects of transplant design that are
      critical to establishing the causes of RL, especially incorporating transplant
      sites at, and source populations from, the range edge. We then conduct a meta
      analysis of published beyond-range transplant experiments (n = 11 tests). Most
      tests (75%) found that performance declined beyond the range, with the strongest
      declines detected when the measure of performance was lifetime fitness (83%),
      suggesting that RL commonly involve niche constraints (declining habitat
      quality). However, only 46% supported range limits occurring at NL; 26% (mostly
      geographic RL) fell short of NL with self-sustaining transplants beyond the
      range, and 23% (all elevational RL) exceeded NL with range-edge populations
      acting as demographic sinks. These data suggest an important but divergent role
      for dispersal, which may commonly constrain geographic distributions while
      extending elevational limits. Meta-analysis results also supported the importance
      of biotic interactions at RL, particularly the long-held assertion of their role
      in causing low-elevation and equatorial limits.

PMID- 24464193
TI  - A tale of two phylogenies: comparative analyses of ecological interactions.
AB  - The evolution of traits involved in ecological interactions such as predator
      prey, host-parasite, and plant-pollinator interactions, are likely to be shaped
      by the phylogenetic history of both parties. We develop generalized linear mixed
      effects models (GLMM) that estimate the effect of both parties' phylogenetic
      history on trait evolution, both in isolation but also in terms of how the two
      histories interact. Using data on the incidence and abundance of 206 flea species
      on 121 mammal species, we illustrate our method and compare it to previously used
      methods for detecting host-parasite coevolution. At large spatial scales we find
      that the phylogenetic interaction effect was substantial, indicating that related
      parasite species were more likely to be found on related host species. At smaller
      spatial scales, and when sampling effort was not controlled for, phylogenetic
      effects on the number and types of parasite species harbored by hosts were found
      to dominate. We go on to show that in situations where these additional
      phylogenetic effects exist, then previous methods have very high Type I error
      rates when testing for the phylogenetic interaction. Our GLMM method represents a
      robust and reliable approach to quantify the phylogenetic effects of traits
      determined by, or defined by, ecological interactions and has the advantage that
      it can easily be extended and interpreted in a broader context than existing
      permutation tests.

PMID- 24464194
TI  - Life-history differences favor evolution of male dimorphism in competitive games.
AB  - Many species exhibit two discrete male morphs: fighters and sneakers. Fighters
      are large and possess weapons but may mature slowly. Sneakers are small and have
      no weapons but can sneak matings and may mature quickly to start mating earlier
      in life than fighters. However, how differences in competitive ability and life
      history interact to determine male morph coexistence has not yet been
      investigated within a single framework. Here we integrate demography and game
      theory into a two-sex population model to study the evolution of strategies that
      result in the coexistence of fighters and sneakers. We incorporate differences in
      maturation time between the morphs and use a mating-probability matrix analogous
      to the classic hawk-dove game. Using adaptive dynamics, we show that male
      dimorphism evolves more easily in our model than in classic game theory
      approaches. Our results also revealed an interaction between life-history
      differences and sneaker competitiveness, which shows that demography and
      competitive games should be treated as interlinked mechanisms to understand the
      evolution of male dimorphism. Applying our approach to empirical data on bulb
      mites (Rhizoglyphus robini), coho salmon (Oncorhynchus kisutch), and bullhorned
      dung beetles (Onthophagus taurus) indicates that observed occurrences of male
      dimorphism are in general agreement with model predictions.

PMID- 24464195
TI  - Variation between self- and mutual assessment in animal contests.
AB  - Limited resources lead animals into conflicts of interest, which are resolved
      when an individual withdraws from a direct contest. Current theory suggests that
      the decision to withdraw can be based on a threshold derived from an individual's
      own state (self-assessment) or on a comparison between their own state and their
      opponent's (mutual assessment). The observed variation between these assessment
      strategies in nature does not conform to theory. Thus, we require theoretical
      developments that explain the functional significance of different assessment
      strategies. We consider a hawk-dove game with two discrete classes that differ in
      fighting ability, in which the players strategically decide on their investment
      toward mutual assessment. Analysis of the model indicates that there are
      simultaneous trade-offs relating to assessment strategies. First, weak
      individuals in a population must decide on whether to acquire information about
      their opponents at the cost of providing opponents with information about
      themselves. Secondly, all individuals must decide between investing in mutual
      assessment and being persistent in contests. Our analysis suggests that the
      potential for individuals to make errors during contests and differences in the
      consequences of sharing information within a population may serve as fundamental
      concepts for explaining variation in assessment strategy.

PMID- 24464196
TI  - Uneven sampling and the analysis of vocal performance constraints.
AB  - Studies of trilled vocalizations provide a premiere illustration of how
      performance constraints shape the evolution of mating displays. In trill
      production, vocal tract mechanics impose a trade-off between syllable repetition
      rate and frequency bandwidth, with the trade-off most pronounced at higher values
      of both parameters. Available evidence suggests that trills that simultaneously
      maximize both traits are more threatening to males or more attractive to females,
      consistent with a history of sexual selection favoring high-performance trills.
      Here, we identify a sampling limitation that confounds the detection and
      description of performance trade-offs. We reassess 70 data sets (from 26
      published studies) and show that sampling limitations afflict 63 of these to some
      degree. Traditional upper-bound regression, which does not control for sampling
      limitations, detects performance trade-offs in 33 data sets; yet when sampling
      limitations are controlled, performance trade-offs are detected in only 15.
      Sampling limitations therefore confound more than half of all performance trade
      offs reported using the traditional method. An alternative method that
      circumvents this sampling limitation, which we explore here, is quantile
      regression. Our goal is not to question the presence of mechanical trade-offs on
      trill production but rather to reconsider how these trade-offs can be detected
      and characterized from acoustic data.

PMID- 24464197
TI  - Predation on pollinators promotes coevolutionary divergence in plant-pollinator
      mutualisms.
AB  - Coevolution of plants and pollinators has been suggested as a mechanism driving
      diversification of plant-pollinator mutualisms. There is increasing recognition
      that predators or competitors can influence the abundance and behavior of
      pollinators and indirectly affect the fitness of plants. However, existing
      theories on plant-pollinator diversification focus exclusively on mutualistic
      interactions between plants and pollinators. Here we used simulations to evaluate
      whether predation on pollinators promotes coevolutionary diversification of plant
      pollinator mutualisms. We developed an individual-based simulation model in which
      the blooming season of plants and the active seasons of pollinators and predators
      can evolve. In simulations without predators, plant-pollinator coevolution caused
      diversification in blooming/active seasons for both plants and pollinators, but
      this diversification resulted in polymorphisms, not speciation. The introduction
      of predators promoted a split of plant and pollinator populations into
      reproductively isolated subpopulations with corresponding blooming and active
      seasons or a directional shift of blooming and active seasons, increasing the
      possibility of plant-pollinator cospeciation. This result suggests that predation
      on pollinators can promote sympatric and allopatric divergence of plant
      pollinator mutualisms. Joint action of antagonistic and mutualistic interactions
      may be fundamentally important for diversification in coevolutionary
      interactions.

PMID- 24464198
TI  - Effects of climate change on trait-based dynamics of a top predator in freshwater
      ecosystems.
AB  - Predicted universal responses of ectotherms to climate warming include increased
      maximum population growth rate and changes in body size through the temperature
      size rule. However, the mechanisms that would underlie these predicted responses
      are not clear. Many studies have focused on proximate mechanisms of physiological
      processes affecting individual growth. One can also consider ultimate mechanisms
      involving adaptive explanations by evaluating temperature effects on different
      vital rates across the life history and using the information in a population
      dynamical model. Here, we combine long-term data for a top predator in freshwater
      ecosystems (pike; Esox lucius) with a stochastic integral projection model to
      analyze concurrent effects of temperature on vital rates, body size, and
      population dynamics. As predicted, the net effect of warming on population growth
      rate (fitness) is positive, but the thermal sensitivity of this rate is highly
      size- and vital rate-dependent. These results are not sensitive to increasing
      variability in temperature. Somatic growth follows the temperature-size rule, and
      our results support an adaptive explanation for this response. The stable length
      structure of the population shifts with warming toward an increased proportion of
      medium-sized but a reduced proportion of small and large individuals. This study
      highlights how demographic approaches can help reveal complex underlying
      mechanisms for population responses to warming.

PMID- 24464199
TI  - Ecological and mutation-order speciation in digital organisms.
AB  - Reproductive isolation between populations often evolves as a by-product of
      independent adaptation to new environments, but the selective pressures of these
      environments may be divergent ("ecological speciation" or uniform ("mutation
      order speciation." In this study, we use an artificial life platform to directly
      compare the strength of reproductive isolation (specifically, postzygotic)
      generated by ecological and mutation-order processes. We also tested the effect
      of gene flow as well as the dimensionality (i.e., number of selective pressures)
      of the environments on the strength of postzygotic isolation. We found that
      ecological speciation generally formed stronger isolation than mutation-order
      speciation, mutation-order speciation was more sensitive to gene flow than
      ecological speciation, and environments with high dimensionality formed stronger
      reproductive isolation than those with low dimensionality. How various factors
      affect the strength of reproductive isolation has been difficult to test in
      biological organisms, but the use of artificial life, which provides its own
      genetic system that evolves, allowed us to computationally test the effect of
      these factors more easily.

PMID- 24464200
TI  - Melanin-specific life-history strategies.
AB  - The maintenance of genetic variation is a long-standing issue because the
      adaptive value of life-history strategies associated with each genetic variant is
      usually unknown. However, evidence for the coexistence of alternative
      evolutionary fixed strategies at the population level remains scarce. Because in
      the tawny owl (Strix aluco) heritable melanin-based coloration shows different
      physiological and behavioral norms of reaction, we investigated whether
      coloration is associated with investment in maintenance and reproduction. Light
      melanic owls had lower adult survival compared to dark melanic conspecifics, and
      color variation was related to the trade-off between offspring number and
      quality. When we experimentally enlarged brood size, light melanic males produced
      more fledglings but in poorer condition, and they were less often recruited in
      the local breeding population than those of darker melanic conspecifics. Our
      results also suggest that dark melanic males allocate a constant effort to raise
      their brood independently of environmental conditions, whereas lighter melanic
      males finely adjust reproductive effort in relation to changes in environmental
      conditions. Color traits can therefore be associated with life-history
      strategies, and stochastic environmental perturbation can temporarily favor one
      phenotype over others. The existence of fixed strategies implies that some
      phenotypes can sometimes display a "maladapted" strategy. Long-term population
      monitoring is therefore vital for a full understanding of how different genotypes
      deal with trade-offs.

PMID- 24464201
TI  - The relationship between morphological and behavioral mimicry in hover flies
      (Diptera: Syrphidae).
AB  - Palatable (Batesian) mimics of unprofitable models could use behavioral mimicry
      to compensate for the ease with which they can be visually discriminated or to
      augment an already close morphological resemblance. We evaluated these
      contrasting predictions by assaying the behavior of 57 field-caught species of
      mimetic hover flies (Diptera: Syrphidae) and quantifying their morphological
      similarity to a range of potential hymenopteran models. A purpose-built phylogeny
      for the hover flies was used to control for potential lack of independence due to
      shared evolutionary history. Those hover fly species that engage in behavioral
      mimicry (mock stinging, leg waving, wing wagging) were all large wasp mimics
      within the genera Spilomyia and Temnostoma. While the behavioral mimics assayed
      were good morphological mimics, not all good mimics were behavioral mimics.
      Therefore, while the behaviors may have evolved to augment good morphological
      mimicry, they do not advantage all good mimics.

PMID- 24464202
TI  - Parallelism isn't perfect: could disease and flooding drive a life-history
      anomaly in Trinidadian guppies?
AB  - Nonparallel evolution, where independent populations occupy similar environments
      but show phenotypic differences, can uncover previously ignored selective
      factors. We investigated a nonparallelism in the life-history strategy of a
      Trinidadian guppy population, a system famous for parallel adaptation to
      differences in predation risk. We tested the hypothesis that high mortality
      drives an observed fast life-history pattern (i.e., earlier maturation and more
      frequent reproductive events) that is atypical for a low-predation environment.
      Using mark-recapture techniques, we compared neighboring low-predation
      populations, finding significantly higher mortality rates in the population with
      atypical life-history traits. Mortality was elevated during the wet season, when
      flooding was common. Moreover, individuals from the anomalous population were
      more likely to transition from healthy to infected disease states. Our results
      stand out against previous patterns observed in this system, indicating that
      higher mortality caused by disease and flooding may have selected for a faster
      life history. Thus, we highlight that even in systems famous for parallel
      adaptation, variation in selective pressures can result in nonparallel phenotypic
      evolution.

PMID- 24464203
TI  - Group size and social conflict in complex societies.
AB  - Conflicts of interest over resources or reproduction among individuals in a
      social group have long been considered to result in automatic and universal costs
      to group living. However, exploring how social conflict varies with group size
      has produced mixed empirical results. Here we develop a model that generates
      alternative predictions for how social conflict should vary with group size
      depending on the type of benefits gained from being in a social group. We show
      that a positive relationship between social conflict and group size is favored
      when groups form primarily for the benefits of sociality but not when groups form
      mainly for accessing group-defended resources. Thus, increased social conflict in
      animal societies should not be viewed as an automatic cost of larger social
      groups. Instead, studying the relationship between social conflict and the types
      of grouping benefits will be crucial for understanding the evolution of complex
      societies.

PMID- 24464205
TI  - Synchrony in malaria infections: how intensifying within-host competition can be
      adaptive.
AB  - Malaria parasites exhibit great diversity in the coordination of their asexual
      life cycle within the host, ranging from asynchronous growth to tightly
      synchronized cycles of invasion and emergence from red blood cells. Synchronized
      reproduction should come at a high cost--intensifying competition among offspring
      -so why would some Plasmodium species engage in such behavior and others not? We
      use a delayed differential equation model to show that synchronized infections
      can be favored when (1) there is limited interference among parasites competing
      for red blood cells, (2) transmission success is an accelerating function of
      sexual parasite abundance, (3) the target of saturating immunity is short-lived,
      and (4) coinfections with asynchronous parasites are rare. As a consequence,
      synchrony may be beneficial or costly, in line with the diverse patterns of
      synchronization observed in natural and lab infections. By allowing us to
      characterize diverse temporal dynamics, the model framework provides a basis for
      making predictions about disease severity and for projecting evolutionary
      responses to interventions.

PMID- 24464206
TI  - Coflowering community context influences female fitness and alters the adaptive
      value of flower longevity in Mimulus guttatus.
AB  - A major goal in evolutionary biology is to incorporate the complexity of
      multispecies interactions into our understanding of microevolutionary processes
      within populations. Although considerable work has been done on antagonistic
      interactions (e.g., plant-herbivore), little attention has been paid to the
      evolutionary implications of context dependency in mutualistic interactions
      (e.g., plant-pollinator). In this study, we use seep communities to evaluate how
      coflowering species richness affects key aspects of pollination (visitation rate
      and conspecific and heterospecific pollen receipt) of Mimulus guttatus. We
      assessed the importance of coflowering diversity in mediating floral evolution by
      determining whether species richness was associated with variation in flower
      size, longevity, and stigma-anther distance and by conducting a reciprocal
      transplant experiment in two contrasting pollination environments. We found lower
      visitation rates and higher heterospecific pollen transfer to M. guttatus growing
      in high-diversity coflowering communities compared to low-diversity coflowering
      communities. We found a positive correlation between flower longevity and
      coflowering species richness. Furthermore, our reciprocal transplant experiment
      showed that extended flower longevity was advantageous only in high-diversity
      seeps and identified coflowering diversity as the most likely selective agent.
      Our results suggest that coflowering diversity can promote floral trait
      differentiation among populations, in this case, flower longevity.

PMID- 24464207
TI  - In memoriam. Ruth Patrick (1907-2013).

PMID- 24464208
TI  - Delayed endoscopic papillary large balloon dilation after sphincterotomy for
      removing large bile duct stones in patients with acute cholangitis.
AB  - BACKGROUND: Endoscopic papillary large balloon dilation (EPLBD) after an
      endoscopic sphincterotomy (EST) is an option for endoscopic removal of large
      common bile duct (CBD) stones. However, risks or fear of severe adverse events
      remain. AIMS: Our aim was to compare the safety and efficacy of delayed EPLBD
      after EST with concurrent EST and EPLBD in patients with acute cholangitis by
      large CBD stones. PATIENTS AND METHODS: A total of sixty-eight patients with
      acute cholangitis from large CBD stones were enrolled in this prospective
      observational study. Thirty-five patients underwent concurrent EST and EPLBD at
      the same session (group A). Thirty-three patients underwent only EST at the first
      session, and EPLBD with stone removal was performed during a second session
      (group B). The complete stone removal rate and adverse events rate were analyzed.
      RESULTS: Both groups resulted in similar outcomes in terms of overall successful
      stone removal (100% in both groups) and the use of additional lithotripsy (22.9%
      in group A and 24.2% in group B). Six patients (17.1%) in group A had procedural
      related adverse events including one patient with death by perforation, one with
      significant bleeding, and four with pancreatitis, including one moderate grade.
      However, there was no procedure-related complication in group B (p < 0.05).
      CONCLUSIONS: Delayed EPLBD after EST may reduce complications associated with
      EPLBD and extraction of large bile duct stones in patients with acute
      cholangitis.

PMID- 24464209
TI  - Epstein-Barr virus (EBV) related acute liver failure: a case series from the US
      Acute Liver Failure Study Group.
AB  - PURPOSE: Acute liver failure (ALF) is a rare clinical syndrome associated with a
      high case fatality rate. Asymptomatic primary infection with Epstein-Barr virus
      (EBV) is common in the general population while acute hepatitis and jaundice are
      much less common and ALF has been rarely reported. We reviewed the presenting
      features as well as clinical outcomes amongst consecutive adults with EBV-related
      ALF. METHODS: Amongst the 1,887 adult ALF patients enrolled into the US ALF Study
      Group from January 1998 to February 2012, there were four patients (0.21 %) with
      EBV-related ALF. Diagnostic criteria for acute EBV infection included compatible
      serologies and/or the detection of EBV-encoded RNA (EBER) in liver tissue.
      RESULTS: Median patient age was 30 years (range 18-44); 75 % were male, and only
      25 % were immunosuppressed. The median presenting ALT was 504 IU/mL (range 156
      4,920), median Alk P was 431 (range 136-1,009), and median bilirubin was 17 mg/dL
      (range 13-22.1). Liver biopsy findings ranged from cholestasis to submassive
      necrosis with EBER + staining in two of the three samples tested. Although all of
      the patients were treated with an antiviral agent, two died of ALF, one underwent
      liver transplantation (LT) and one survived with supportive care and is well at 5
      years. A review of the literature identified four additional LT recipients with
      favorable long-term outcomes. CONCLUSION: Primary EBV infection accounts for <1 %
      of consecutive adult ALF cases but is associated with a high case fatality rate.
      LT is associated with favorable short- and long-term outcomes.

PMID- 24464210
TI  - An illness without geographic boundaries.

PMID- 24464211
TI  - OxNASH score correlates with histologic features and severity of nonalcoholic
      fatty liver disease.
AB  - BACKGROUND AND AIM: Oxidative stress is a core abnormality responsible for
      disease progression in nonalcoholic fatty liver disease (NAFLD). By employing a
      highly sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS)
      approach we recently were able to define the circulating profile of bioactive
      lipid peroxidation products characteristic of patients with nonalcoholic
      steatohepatitis (NASH) and developed the OxNASH score for NASH diagnosis. The
      aims of this study were to assess the utility of OxNASH as a predictor of NASH
      and study the association between OxNASH and specific histologic features of
      NAFLD. METHODS: Our cohort consisted of 122 patients undergoing liver biopsy for
      clinical suspicion of NAFLD. The NAFLD activity score (NAS) was calculated for
      each patient. Levels of fatty acid oxidation products were quantified using
      stable isotope dilution LC/MS/MS, and OxNASH was calculated. RESULTS: The mean
      age of our patients was 49.3 (+/-11.6) years, and the mean body mass index was
      31.5 (+/-4.8) kg/m(2). The majority of patients were Caucasian (82 %) and 48 %
      were female. OxNASH correlated with NAS and with the individual histologic
      features of NAFLD, namely, steatosis, inflammation, and ballooning (P < 0.05),
      with the strongest association being with inflammation [rho (rho) 0.40, 95 %
      confidence interval 0.23, 0.57, P < 0.001]. There was also a correlation between
      the stage of fibrosis and OxNASH (P = 0.001). These associations remained
      statistically significant after adjustment for multiple confounders. CONCLUSIONS:
      Based on our results, in adult patients with NAFLD, OxNASH correlates with
      histologic features of NASH and appears to be a promising noninvasive marker.

PMID- 24464212
TI  - HOXA10 promotes cell invasion and MMP-3 expression via TGFbeta2-mediated
      activation of the p38 MAPK pathway in pancreatic cancer cells.
AB  - BACKGROUND: HOXA10 is closely related to tumor progression in many human cancers.
      However, the role of HOXA10 in pancreatic cancer remains unclear. The aim of this
      study was to determine the involvement of HOXA10 in pancreatic cancer cell
      invasion and migration. METHODS: The effect of HOXA10 on the invasion and
      migration of pancreatic cancer cells was assessed by invasion and migration
      assays. The protein of transforming growth factor beta-2 (TGFbeta2) was
      neutralized by TGFbeta2 blocking antibody. The activation of p38 was inhibited by
      SB239063. RESULTS: HOXA10 could promote the invasion and migration of pancreatic
      cancer cells. Knockdown of HOXA10 decreased the expressions of TGFbeta2 and
      matrix metallopeptidase-3 (MMP-3) and suppressed the activation of p38.
      Conversely, overexpression of HOXA10 increased the levels of TGFbeta2 and MMP-3.
      Further experiments identified that TGFbeta2 contributed to the HOXA10-promoted
      invasion and migration and regulated MMP-3 expression and p38 activation.
      Additionally, inhibition of p38 suppressed cell invasion and MMP-3 expression in
      pancreatic cancer cells. CONCLUSIONS: HOXA10 promotes cell invasion and MMP-3
      expression of pancreatic cancer cells via TGFbeta2-p38 MAPK pathway. Thus, HOXA10
      could be a useful target for the treatment of pancreatic cancer.

PMID- 24464213
TI  - Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular
      carcinoma.
AB  - Checkpoint kinase 1 (CHEK1) is an evolutionarily conserved Ser/Thr kinase, which
      mediates cell-cycle arrest after DNA damage, and we previously reported that
      CHEK1 was overexpressed and associated with poor prognosis in hepatocellular
      carcinoma (HCC), indicating it was oncogenic gene. In this study, we aimed to
      elucidate the mechanism of CHEK1 overexpression in HCC. We first verified the
      upregulated CHEK1 by qRT-PCR and western blot in 30 HCC samples compared with
      corresponding non-tumor liver tissues. In silico analysis showed that CHEK1 was a
      candidate target of miR-497, which was previously found to be downregulated in
      HCC by us. To test whether miR-497 could bind to 3'untranslated region (3'UTR) of
      CHEK1, luciferase reporter assay was conducted. The result revealed that miR-497
      could bind to the 3'untranslated region (3'UTR) of CHEK1 mRNA. Western blot
      showed that ectopic expression of miR-497 suppressed the CHEK1 expression and
      inhibition of miR-497 led to significant upregulation of CHEK1. Finally, miR-497
      expression was measured in the same 30 HCC samples, and the correlation between
      miR-497 and CHEK1 was analyzed. The results indicated that miR-497 was
      downregulated in HCC and had a significant negative correlation with CHEK1. Taken
      together, these results demonstrated that CHEK1 was negatively regulated by miR
      497, and the overexpressed CHEK1 was resulted from the downregulated miR-497 in
      HCC, which provided a potential molecular target for HCC therapy. 

PMID- 24464215
TI  - Tailoring the self-assembled structures and photonic properties of organic
      nanomaterials.
AB  - Organic nanomaterials have attracted more and more attention for their
      applications in nano-photonics due to their high photoluminescence quantum
      efficiencies, color tunabilities, and size-dependent optical properties. With the
      distinctive features of photoluminescence, waveguiding and dimensional
      confinement, different organic nanostructures, such as 0D nanoparticles, 1D
      nanowires and 2D nanosheets, have a significant influence on their photonic
      properties. Therefore, it is of great importance and scientific interest to
      develop the strategy for tailoring the self-assembled structures with specific
      photonic behaviors in desired manners. In this mini review, we give a brief
      review of the recent work on the control of self-assembled organic
      nanostructures, and the tunable photonic properties of the predetermined
      structures. 

PMID- 24464214
TI  - Hepato-biliary-enteric stent drainage as palliative treatment for proximal
      malignant obstructive jaundice.
AB  - The proximal malignant obstructive jaundice remains one of the most challenging
      problems for hepato-biliary surgeons. Particularly when the findings preclude
      surgical resection at exploration, the next decision seems hard to make. A novel
      palliative treatment called "hepato-biliary-enteric stent drainage" was designed
      for these proximal malignant obstructive jaundice patients. Hepato-biliary
      enteric stent drainage was performed with silicone tube whose diameter was
      determined according to the degree of dilated biliary ducts, and the proximal end
      of the tube was placed to intrahepatic ducts as far as possible, the distal end
      was placed across the duodenal papilla. Between February 2011 and August 2012, 23
      patients with the proximal malignant obstructive jaundice of unresectable tumors
      at exploration received hepato-biliary-enteric stent drainage. Patient's liver
      function results, symptoms, complications, and survival time were documented. The
      bilirubin levels of all 23 patients had a considerable and persistent decrease
      after operation and remained low or normal before death except for four cases of
      recurrent jaundice (two resulted from migration of tube and other two resulted
      from hepatocellular carcinoma extensively involving liver parenchyma). After
      effective drainage, clinical symptoms of cholangitis such as fever or pain were
      markedly relieved. No procedure-related bleeding, bile leakage, pancreatitis were
      observed. The median survival time was 212 days, half-year and 1-year survival
      rate were 56.5 and 21.7%, respectively. Hepato-biliary-enteric stent drainage
      with less expense, less complications, and easy operation may be an ideal option
      for patients with unresectable malignancy in the hilar region at exploration.

PMID- 24464216
TI  - Computer-aided diagnosis of hyperacute stroke with thrombolysis decision support
      using a contralateral comparative method of CT image analysis.
AB  - New and improved techniques have been continuously introduced into CT and MR
      imaging modalities for the diagnosis and therapy planning of acute stroke.
      Nevertheless, non-contrast CT (NCCT) is almost always used by every institution
      as the front line diagnostic imaging modality due to its high affordability and
      availability. Consequently, the potential reward of extracting as much clinical
      information as possible from NCCT images can be very great. Intravenous tissue
      plasminogen activator (tPA) has become the gold standard for treating acute
      ischemic stroke because it is the only acute stroke intervention approved by the
      FDA. ASPECTS scoring based on NCCT images has been shown to be a reliable scoring
      method that helps physicians to make sound decisions regarding tPA
      administration. In order to further reduce inter-observer variation, we have
      developed the first end-to-end automatic ASPECTS scoring system using a novel
      method of contralateral comparison. Due to the self-adaptive nature of the
      method, our system is robust and has good generalizability. ROC analysis based on
      evaluation of 103 subjects who presented to the stroke center of Chang Gung
      Memorial Hospital with symptoms of acute stroke has shown that our system's
      dichromatic classification of patients into thrombolysis indicated or
      thrombolysis contraindicated groups has achieved a high accuracy rate with AUC
      equal to 90.2 %. The average processing time for a single case is 170 s. In
      conclusion, our system has the potential of enhancing quality of care and
      providing clinical support in the setting of a busy stroke or emergency center. 

PMID- 24464217
TI  - Therapeutic implication of L-phenylalanine aggregation mechanism and its
      modulation by D-phenylalanine in phenylketonuria.
AB  - Self-assembly of phenylalanine is linked to amyloid formation toxicity in
      phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles
      to amyloid fibrils at varying experimental conditions and transforms to a gel
      state at saturated concentration. Biophysical methods including nuclear magnetic
      resonance, resistance by alpha-phenylglycine to fibril formation and preference
      of protected phenylalanine to self-assemble show that this behaviour of L
      phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D
      phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to
      flakes. These flakes do not propagate further and prevent fibre formation by L
      phenylalanine. This suggests the use of D-phenylalanine as modulator of L
      phenylalanine amyloid formation and may qualify as a therapeutic molecule in
      phenylketonuria. 

PMID- 24464218
TI  - Apical periodontitis and periodontal disease increase serum IL-17 levels in
      normoglycemic and diabetic rats.
AB  - OBJECTIVES: This study aimed to evaluate the influence of apical periodontitis
      (AP) and/or periodontal disease (PD) on serum interleukin-17 (IL-17) levels in a
      rat model of diabetes mellitus (DM). METHODS: Eighty male Wistar rats were
      divided into eight groups of ten animals each: normoglycemic, AP, PD, AP+PD, DM,
      DM+AP, DM+PD, and DM+AP+PD. DM was induced using streptozotocin, AP by dental
      pulp exposure to the oral environment, and PD by periodontal ligature. The
      animals were sacrificed after 30 days, and venous blood samples were collected
      via cardiac puncture to determine the serum IL-17 and neutrophil levels. The
      maxillae were dissected and processed for radiographic analysis. The periapical
      lesion areas were quantified in pixels. The total assessed values were tabulated
      according to each experimental group and were statistically analyzed using
      Spearman's correlation and Kruskal-Wallis test (p < 0.05). RESULTS: A significant
      difference in the serum IL-17 levels was observed between the groups without oral
      infections and the groups with AP+PD-associated lesions, regardless of the
      presence of DM (p < 0.05). Diabetes increased the neutrophil levels, regardless
      of the presence of oral infection. However, a combination of two oral infections
      increased the neutrophil levels in DM rats (p < 0.05). The level of bone
      resorption lesions was greater in DM rats than in normoglycemic rats (p < 0.05).
      CONCLUSION: The combination of AP and PD increased the serum IL-17 levels in DM
      and normoglycemic rats and increased the neutrophil levels in DM rats. Diabetes
      increased the neutrophil levels and bone resorption in rats. CLINICAL
      SIGNIFICANCE: AP is capable of potentiating systemic inflammatory changes when
      associated with PD, and increases in blood glucose can accelerate the
      pathogenesis of oral infections.

PMID- 24464219
TI  - Fra-2/AP-1 controls adipocyte differentiation and survival by regulating
      PPARgamma and hypoxia.
AB  - Adipocyte cell number is a crucial factor for controlling of body weight and
      metabolic function. The regulation of adipocyte numbers in the adult organism is
      not fully understood but is considered to depend on the homeostasis of cell
      differentiation and apoptosis. Herein, we show that targeted deletion of the
      activator protein (AP-1)-related transcription factor Fra-2 in adipocytes in vivo
      (Fra-2(Deltaadip) mice) induces a high-turnover phenotype with increased
      differentiation and apoptosis of adipocytes, leading to a decrease in body weight
      and fat pad mass. Importantly, adipocyte cell numbers were significantly reduced
      in Fra-2(Deltaadip) mice. At the molecular level, Fra-2 directly binds to the
      PPARgamma2 promoter and represses PPARgamma2 expression. Deletion of Fra-2 leads
      to increased PPARgamma2 expression and adipocyte differentiation as well as
      increased adipocyte apoptosis through upregulation of hypoxia-inducible factors
      (HIFs). These findings suggest that Fra-2 is an important checkpoint to control
      adipocyte turnover. Therefore, inhibition of Fra-2 may emerge as a useful
      strategy to increase adipocyte turnover and to reduce adipocyte numbers and fat
      mass in the body. 

PMID- 24464220
TI  - Loss of Bak enhances lymphocytosis but does not ameliorate thrombocytopaenia in
      BCL-2 transgenic mice.
AB  - Bax and Bak are critical effectors of apoptosis. Although both are widely
      expressed and usually functionally redundant, recent studies suggest that Bak has
      particular importance in certain cell types. Genetic and biochemical studies
      indicate that Bak activation is prevented primarily by Mcl-1 and Bcl-xL, whereas
      Bax is held in check by all pro-survival Bcl-2 homologues, including Bcl-2
      itself. In this study, we have investigated whether loss of Bak or elevated Mcl-1
      modulates haemopoietic abnormalities provoked by overexpression of Bcl-2. The Mcl
      1 transgene had little impact, probably because the expression level was
      insufficient to effectively reduce Bak activation. However, loss of Bak enhanced
      lymphocytosis in vavP-BCL-2 transgenic mice and increased resistance of their
      thymocytes to some cytotoxic agents, implying that Bak-specific signals can be
      triggered in certain lymphoid populations. Nevertheless, lack of Bak had no
      significant impact on thymic abnormalities in vavP-BCL-2tg mice, which kinetic
      analysis suggested was due to accumulation of self-reactive thymocytes that
      resist deletion. Intriguingly, although Bak(-/-) mice have elevated platelet
      counts, Bak(-/-)vavP-BCL-2 mice, like vavP-BCL-2 littermates, were
      thrombocytopaenic. To clarify why, the vavP-BCL-2 platelet phenotype was
      scrutinised more closely. Platelet life span was found to be elevated in vavP-BCL
      2 mice, which should have provoked thrombocytosis, as in Bak(-/-) mice. Analysis
      of bone marrow chimaeric mice suggested the low platelet phenotype was due
      principally to extrinsic factors. Following splenectomy, blood platelets remained
      lower in vavP-BCL-2 than wild-type mice. However, in Rag1(-/-) BCL-2tg mice,
      platelet levels were normal, implying that elevated lymphocytes are primarily
      responsible for BCL-2tg-induced thrombocytopaenia. 

PMID- 24464221
TI  - Oxidatively modified phosphatidylserines on the surface of apoptotic cells are
      essential phagocytic 'eat-me' signals: cleavage and inhibition of phagocytosis by
      Lp-PLA2.
AB  - Diversified anionic phospholipids, phosphatidylserines (PS), externalized to the
      surface of apoptotic cells are universal phagocytic signals. However, the role of
      major PS metabolites, such as peroxidized species of PS (PSox) and lyso-PS, in
      the clearance of apoptotic cells has not been rigorously evaluated. Here, we
      demonstrate that H2O2 was equally effective in inducing apoptosis and
      externalization of PS in naive HL60 cells and in cells enriched with oxidizable
      polyunsaturated species of PS (supplemented with linoleic acid (LA)). Despite
      this, the uptake of LA-supplemented cells by RAW264.7 and THP-1 macrophages was
      more than an order of magnitude more effective than that of naive cells. A
      similar stimulation of phagocytosis was observed with LA-enriched HL60 cells and
      Jurkat cells triggered to apoptosis with staurosporine. This was due to the
      presence of PSox on the surface of apoptotic LA-supplemented cells (but not of
      naive cells). This enhanced phagocytosis was dependent on activation of the
      intrinsic apoptotic pathway, as no stimulation of phagocytosis occurred in LA
      enriched cells challenged with Fas antibody. Incubation of apoptotic cells with
      lipoprotein-associated phospholipase A2 (Lp-PLA2), a secreted enzyme with high
      specificity towards PSox, hydrolyzed peroxidized PS species in LA-supplemented
      cells resulting in the suppression of phagocytosis to the levels observed for
      naive cells. This suppression of phagocytosis by Lp-PLA2 was blocked by a
      selective inhibitor of Lp-PLA2, SB-435495. Screening of possible receptor
      candidates revealed the ability of several PS receptors and bridging proteins to
      recognize both PS and PSox, albeit with diverse selectivity. We conclude that
      PSox is an effective phagocytic 'eat-me' signal that participates in the
      engulfment of cells undergoing intrinsic apoptosis. 

PMID- 24464222
TI  - Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of
      mitochondrial dysfunction.
AB  - Isthmin (ISM) is a secreted 60-kDa protein that potently induces endothelial cell
      (EC) apoptosis. It suppresses tumor growth and angiogenesis in mice when stably
      overexpressed in cancer cells. Although alphavbeta5 integrin serves as a low
      affinity receptor for ISM, the mechanism by which ISM mediates antiangiogenesis
      and apoptosis in ECs remain to be fully resolved. In this work, we report the
      identification of cell-surface glucose-regulated protein 78 kDa (GRP78) as a high
      affinity receptor for ISM (Kd=8.6 nM). We demonstrated that ISM-GRP78 interaction
      triggers apoptosis not only in activated ECs but also in cancer cells expressing
      high level of cell-surface GRP78. Normal cells and benign tumor cells tend to
      express low level of cell-surface GRP78 and are resistant to ISM-induced
      apoptosis. Upon binding to GRP78, ISM is internalized into ECs through clathrin
      dependent endocytosis that is essential for its proapoptotic activity. Once
      inside the cell, ISM co-targets with GRP78 to mitochondria where it interacts
      with ADP/ATP carriers on the inner membrane and blocks ATP transport from
      mitochondria to cytosol, thereby causing apoptosis. Hence, ISM is a novel
      proapoptotic ligand that targets cell-surface GRP78 to trigger apoptosis by
      inducing mitochondrial dysfunction. The restricted and high-level expression of
      cell-surface GRP78 on cancer cells and cancer ECs make them uniquely susceptible
      to ISM-targeted apoptosis. Indeed, systemic delivery of recombinant ISM potently
      suppressed subcutaneous 4T1 breast carcinoma and B16 melanoma growth in mice by
      eliciting apoptosis selectively in the cancer cells and cancer ECs. Together,
      this work reveals a novel ISM-GRP78 apoptosis pathway and demonstrates the
      potential of ISM as a cancer-specific and dual-targeting anticancer agent. 

PMID- 24464223
TI  - The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin
      induced cell death in lung adenocarcinoma.
AB  - Intrinsic and acquired chemoresistance are frequent causes of cancer eradication
      failure. Thus, long-term cis-diaminedichloroplatine(II) (CDDP) or cisplatin
      treatment is known to promote tumor cell resistance to apoptosis induction via
      multiple mechanisms involving gene expression modulation of oncogenes, tumor
      suppressors and blockade of pro-apoptotic mitochondrial membrane
      permeabilization. Here, we demonstrate that CDDP-resistant non-small lung cancer
      cells undergo profound remodeling of their endoplasmic reticulum (ER) proteome
      (>80 proteins identified by proteomics) and exhibit a dramatic overexpression of
      two protein disulfide isomerases, PDIA4 and PDIA6, without any alteration in ER
      cytosol Ca(2+) fluxes. Using pharmacological and genetic inhibition, we show that
      inactivation of both proteins directly stimulates CDDP-induced cell death by
      different cellular signaling pathways. PDIA4 inactivation restores a classical
      mitochondrial apoptosis pathway, while knockdown of PDIA6 favors a non-canonical
      cell death pathway sharing some necroptosis features. Overexpression of both
      proteins has also been found in lung adenocarcinoma patients, suggesting a
      clinical importance of these proteins in chemoresistance. 

PMID- 24464224
TI  - DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial
      differentiation and hyperproliferation.
AB  - Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells,
      but contains a small subpopulation of basal cells (including stem-like cells),
      which can proliferate and differentiate into luminal-like cells. In cancers, CpG
      island hypermethylation has been associated with gene downregulation, but the
      causal relationship between the two phenomena is still debated. Here we clarify
      the origin and function of CpG island hypermethylation in CaP, in the context of
      a cancer cell hierarchy and epithelial differentiation, by analysis of separated
      basal and luminal cells from cancers. For a set of genes (including GSTP1) that
      are hypermethylated in CaP, gene downregulation is the result of cell
      differentiation and is not cancer specific. Hypermethylation is however seen in
      more differentiated cancer cells and is promoted by hyperproliferation. These
      genes are maintained as actively expressed and methylation-free in
      undifferentiated CaP cells, and their hypermethylation is not essential for
      either tumour development or expansion. We present evidence for the causes and
      the dynamics of CpG island hypermethylation in CaP, showing that, for a specific
      set of genes, promoter methylation is downstream of gene downregulation and is
      not a driver of gene repression, while gene repression is a result of tissue
      specific differentiation. 

PMID- 24464225
TI  - Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for
      prospermatogonial development in mice.
AB  - The PIWI-piRNA pathway serves as a critical defense mechanism through which the
      genome of the male germline is protected from invasion by transposable elements
      (TEs). MIWI2/PIWIL4, a member of the murine PIWI subclade of the Argonaute
      family, has been shown to be expressed in primordial germ cells (PGCs) and
      prospermatogonia in fetal and prepubertal testes. Global inactivation of Miwi2
      leads to male sterility due to an early meiotic arrest, which correlates with
      retrotransposon desuppression. However, it remains unclear whether MIWI2
      functions beyond the PGC stage and whether MIWI2 has a role beyond TE suppression
      during male germ line development. Through conditional inactivation of Miwi2, we
      demonstrate herein that MIWI2 function is restricted to a narrow time window
      during male PGC reprograming and that Miwi2 is dispensable for postnatal male
      germline development and testicular function in mice. Moreover, persistent
      activation of LINE1 and IAP retrotransposons caused by Miwi2 inactivation is
      compatible with mitotic cell cycle progression of spermatogonia during the first
      wave of spermatogenesis, but can cause zygotene to pachytene arrest in early
      meiosis due to multiple defects including enhanced DNA double-strand breaks,
      aberrant histone modifications and altered mRNA transcriptome. Our data not only
      validate those from global Miwi2 KO studies, but also suggest that MIWI2 and
      MIWI2-associated piRNAs have functions beyond TE suppression. 

PMID- 24464227
TI  - Authors' response.

PMID- 24464226
TI  - A functional genomics screen identifies PCAF and ADA3 as regulators of human
      granzyme B-mediated apoptosis and Bid cleavage.
AB  - The human lymphocyte toxins granzyme B (hGrzB) and perforin cooperatively induce
      apoptosis of virus-infected or transformed cells: perforin pores enable entry of
      the serine protease hGrzB into the cytosol, where it processes Bid to selectively
      activate the intrinsic apoptosis pathway. Truncated Bid (tBid) induces Bax/Bak
      dependent mitochondrial outer membrane permeability and the release of cytochrome
      c and Smac/Diablo. To identify cellular proteins that regulate perforin/hGrzB
      mediated Bid cleavage and subsequent apoptosis, we performed a gene-knockdown
      (KD) screen using a lentiviral pool of short hairpin RNAs embedded within a miR30
      backbone (shRNAmiR). We transduced HeLa cells with a lentiviral pool expressing
      shRNAmiRs that target 1213 genes known to be involved in cell death signaling and
      selected cells with acquired resistance to perforin/hGrzB-mediated apoptosis.
      Twenty-two shRNAmiRs were identified in the positive-selection screen including
      two, PCAF and ADA3, whose gene products are known to reside in the same
      epigenetic regulatory complexes. Small interfering (si)RNA-mediated gene-KD of
      PCAF or ADA3 also conferred resistance to perforin/hGrzB-mediated apoptosis
      providing independent validation of the screen results. Mechanistically, PCAF and
      ADA3 exerted their pro-apoptotic effect upstream of mitochondrial membrane
      permeabilization, as indicated by reduced cytochrome c release in PCAF-KD cells
      exposed to perforin/hGrzB. While overall levels of Bid were unaltered,
      perforin/hGrzB-mediated cleavage of Bid was reduced in PCAF-KD or ADA3-KD cells.
      We discovered that PCAF-KD or ADA3-KD resulted in reduced expression of PACS2, a
      protein implicated in Bid trafficking to mitochondria and importantly, targeted
      PACS2-KD phenocopied the effect of PCAF-KD or ADA3-KD. We conclude that PCAF and
      ADA3 regulate Bid processing via PACS2, to modulate the mitochondrial cell death
      pathway in response to hGrzB. 

PMID- 24464228
TI  - Increased fecal fat and protein intolerance.

PMID- 24464229
TI  - Good agreement between endoscopic findings and biopsy reports supports limited
      tissue sampling during pediatric colonoscopy.
AB  - OBJECTIVES: Colonoscopy in children routinely includes the practice of obtaining
      multiple biopsy samples even in the absence of gross mucosal abnormalities. The
      aim of our investigation was to examine the level of agreement between endoscopic
      and histological findings during pediatric colonoscopy. We also investigated the
      predictors of agreement and abnormal histology. METHODS: We performed an
      institutionally approved retrospective review of consecutive patients who
      underwent diagnostic colonoscopy during a 6-month period. Descriptive analyses
      and regression models were used to determine agreement rates, as well as
      potential predictors of both agreement and abnormal histology. RESULTS: Of 390
      included colonoscopies, endoscopists (n = 26) reported abnormal gross findings in
      218 (56%) and pathologists (n = 4) found histopathology in 195 (50%). Considering
      histology as the criterion standard, endoscopy had a sensitivity of 90% and a
      specificity of 78%. Reports of grossly normal endoscopic findings were highly
      associated with agreement (odds ratio [OR] 1.9, P = 0.001). A known diagnosis of
      inflammatory bowel disease was a strong predictor of abnormal histology (OR 6.4,
      P < 0.0001). Abdominal pain as a procedural indication was a strong predictor for
      normal histology (OR 0.4, P < 0.0001). CONCLUSIONS: The results of our study
      suggest good agreement between endoscopic and histological findings, especially
      when an endoscopist reports normal-appearing colonic mucosa. We identified
      predictors of abnormal histology to include known inflammatory bowel disease,
      whereas abdominal pain was found to be a negative predictor. Future studies are
      needed to determine evidence-based protocols for obtaining biopsies during
      colonoscopy in children.

PMID- 24464230
TI  - Hydrolyzed formulas for allergy prevention.
AB  - OBJECTIVES: The aim of the present review was to provide recommendations on the
      use of hydrolysates in infants when formula feeding is initiated. METHODS: We
      performed an overview of reviews followed by a systematic review of subsequently
      published trials. RESULTS: We found 8 systematic reviews; only 1 study of limited
      quality was published afterwards. Certain extensively hydrolyzed casein and
      certain partially hydrolyzed whey formulas are appropriate for reducing the risk
      of allergy in infants at high risk when formula feeding is initiated.
      CONCLUSIONS: In high-risk infants, when breast-feeding is not possible,
      hydrolysates of documented safety and efficacy have an indication in infant
      feeding up to the age 4 to 6 months.

PMID- 24464231
TI  - Neurofibromin specific antibody differentiates malignant peripheral nerve sheath
      tumors (MPNST) from other spindle cell neoplasms.
AB  - Malignant peripheral nerve sheath tumors (MPNST) derive from the Schwann cell or
      perineurial cell lineage and occur either sporadically or in association with the
      tumor syndrome neurofibromatosis type 1 (NF1). MPNST often pose a diagnostic
      challenge due to their frequent lack of pathognomonic morphological or
      immunohistochemical features. Mutations in the NF1 tumor suppressor gene are
      found in all NF1-associated and many sporadic MPNST. The presence of NF1 mutation
      may have the potential to differentiate MPNST from several morphologically
      similar neoplasms; however, mutation detection is hampered by the size of the
      gene and the lack of mutational hot spots. Here we describe a newly developed
      monoclonal antibody binding to the C-terminus of neurofibromin (clone NFC) which
      was selected for optimal performance in routinely processed formalin-fixed and
      paraffin-embedded tissue. NFC immunohistochemistry revealed loss of neurofibromin
      in 22/25 (88 %) of NF1-associated and 26/61 (43 %) of sporadic MPNST. There was a
      strong association of neurofibromin loss with deletions affecting the NF1 gene (P
      < 0.01). In a series of 256 soft tissue tumors of different histotypes NFC
      staining showed loss of neurofibromin in 2/8 myxofibrosarcomas, 2/12 (16 %)
      pleomorphic liposarcomas, 1/16 (6 %) leiomyosarcomas, and 4/28 (14 %)
      unclassified undifferentiated pleomorphic sarcomas. However, loss of
      neurofibromin was not observed in 22 synovial sarcomas, 27 schwannomas, 23
      solitary fibrous tumors, 14 low-grade fibromyxoid sarcomas, 50 dedifferentiated
      liposarcomas, 27 myxoid liposarcomas, 13 angiosarcomas, 9 extraskeletal myxoid
      chondrosarcomas, and 7 epitheloid sarcomas. Immunohistochemistry using antibody
      NFC may substantially facilitate sarcoma research and diagnostics.

PMID- 24464232
TI  - Cooling effect of rivers on metropolitan Taipei using remote sensing.
AB  - This study applied remote sensing technology to analyze how rivers in the urban
      environment affect the surface temperature of their ambient areas. While surface
      meteorological stations can supply accurate data points in the city, remote
      sensing can provide such data in a two-dimensional (2-D) manner. The goal of this
      paper is to apply the remote sensing technique to further our understanding of
      the relationship between the surface temperature and rivers in urban areas. The 2
      D surface temperature data was retrieved from Landsat-7 thermal infrared images,
      while data collected by Formosat-2 was used to categorize the land uses in the
      urban area. The land surface temperature distribution is simulated by a sigmoid
      function with nonlinear regression analysis. Combining the aforementioned data,
      the range of effect on the surface temperature from rivers can be derived. With
      the remote sensing data collected for the Taipei Metropolitan area, factors
      affecting the surface temperature were explored. It indicated that the effect on
      the developed area was less significant than on the ambient nature zone;
      moreover, the size of the buffer zone between the river and city, such as the
      wetlands or flood plain, was found to correlate with the affected distance of the
      river surface temperature. 

PMID- 24464233
TI  - The incidence of West Nile disease in Russia in relation to climatic and
      environmental factors.
AB  - Since 1999, human cases of West Nile fever/neuroinvasive disease (WND) have been
      reported annually in Russia. The highest incidence has been recorded in three
      provinces of southern European Russia (Volgograd, Astrakhan and Rostov
      Provinces), yet in 2010-2012 the distribution of human cases expanded northwards
      considerably. From year to year, the number of WND cases varied widely, with
      major WND outbreaks in 1999, 2007, 2010, and 2012. The present study was aimed at
      identifying the most important climatic and environmental factors potentially
      affecting WND incidence in the three above-mentioned provinces and at building
      simple prognostic models, using those factors, by the decision trees method. The
      effects of 96 variables, including mean monthly temperature, relative humidity,
      precipitation, Normalized Difference Vegetation Index, etc. were taken into
      account. The findings of this analysis show that an increase of human WND
      incidence, compared to the previous year, was mostly driven by higher
      temperatures in May and/or in June, as well as (to a lesser extent) by high
      August-September temperatures. Declining incidence was associated with cold
      winters (December and/or January, depending on the region and type of model). WND
      incidence also tended to decrease during year following major WND outbreaks.
      Combining this information, the future trend of WND may be, to some extent,
      predicted, in accordance with the climatic conditions observed before the summer
      peak of WND incidence. 

PMID- 24464234
TI  - Relating built environment to physical activity: two failures to validate.
AB  - The Irvine-Minnesota Inventory (IMI) is an audit tool used to record properties
      of built environments. It was designed to explore the relationships between
      environmental features and physical activity. As published, the IMI does not
      provide scoring to support this use. Two papers have since been published
      recommending methods to form scales from IMI items. This study examined these
      scoring procedures in new settings. IMI data were collected in two urban settings
      in Alberta in 2008. Scale scores were calculated using the methods presented in
      previous papers and used to test whether the relationships between IMI scales and
      walking behaviors were consistent with previously reported results. The scales
      from previous work did not show expected relationships with walking behavior. The
      scale construction techniques from previous work were repeated but scales formed
      in this way showed little similarity to previous scales. The IMI has great
      potential to contribute to understanding relationships between built environment
      and physical activity. However, constructing reliable and valid scales from IMI
      items will require further research. 

PMID- 24464235
TI  - Evaluation of respirable crystalline silica in high school ceramics classrooms.
AB  - Air concentrations of respirable crystalline silica were measured in eleven (11)
      high school ceramics classrooms located in Salt Lake County, UT, USA. Respirable
      dust was collected on PVC filters using precision flow pumps and cyclone samplers
      (n = 44). Filters were subsequently analyzed for respirable dust and percent
      crystalline silica content. The geometric mean of the silica concentrations was
      0.009 mg/m3 near the teacher's work station and 0.008 mg/m3 near the kilns. The
      number of students in the classroom was correlated to the silica concentration in
      the ceramics classroom, but no correlation was found between the silica
      concentrations and either the size of the classroom or the age of the building.
      Results from this study indicate that ceramics teachers may be at an increased
      risk of exposure to crystalline silica based on the ACGIH TLV of 0.025 mg/m3,
      with an excess of 21%.

PMID- 24464236
TI  - Embedded fragments from U.S. military personnel--chemical analysis and potential
      health implications.
AB  - BACKGROUND: The majority of modern war wounds are characterized by high-energy
      blast injuries containing a wide range of retained foreign materials of a
      metallic or composite nature. Health effects of retained fragments range from
      local or systemic toxicities to foreign body reactions or malignancies, and
      dependent on the chemical composition and corrosiveness of the fragments in vivo.
      Information obtained by chemical analysis of excised fragments can be used to
      guide clinical decisions regarding the need for fragment removal, to develop
      therapeutic interventions, and to better anticipate future medical problems from
      retained fragment related injuries. In response to this need, a new U.S
      Department of Defense (DoD) directive has been issued requiring characterization
      of all removed fragments to provide a database of fragment types occurring in
      combat injuries. OBJECTIVES: The objective of this study is to determine the
      chemical composition of retained embedded fragments removed from injured military
      personnel, and to relate results to histological findings in tissue adjacent to
      fragment material. METHODS: We describe an approach for the chemical analysis and
      characterization of retained fragments and adjacent tissues, and include case
      examples describing fragments containing depleted uranium (DU), tungsten (W),
      lead (Pb), and non-metal foreign bodies composed of natural and composite
      materials. Fragments obtained from four patients with penetrating blast wounds to
      the limbs were studied employing a wide range of chemical and microscopy
      techniques. Available adjacent tissues from three of the cases were
      histologically, microscopically, and chemically examined. The physical and
      compositional properties of the removed foreign material surfaces were examined
      with energy dispersive x-ray fluorescence spectrometry (EDXRF), scanning electron
      microscopy (SEM), laser ablation inductively-coupled plasma mass-spectrometry (LA
      ICP-MS), and confocal laser Raman microspectroscopy (CLRM). Quantitative chemical
      analysis of both fragments and available tissues was conducted employing ICP-MS.
      RESULTS: Over 800 fragments have been characterized and included as part of the
      Joint Pathology Center Embedded Fragment Registry. Most fragments were obtained
      from penetrating wounds sustained to the extremities, particularly soft tissue
      injuries. The majority of the fragments were primarily composed of a single metal
      such as iron, copper, or aluminum with traces of antimony, titanium, uranium, and
      lead. One case demonstrated tungsten in both the fragment and the connected
      tissue, together with lead. Capsular tissue and fragments from a case from the
      1991 Kuwait conflict showed evidence of uranium that was further characterized by
      uranium isotopic ratios analysis to contain depleted uranium. CONCLUSIONS: The
      present study provides a systematic approach for obtaining a full chemical
      characterization of retained embedded fragments. Given the vast number of combat
      casualties with retained fragments, it is expected that fragment analysis will
      have significant implications for the optimal short and long-term care of wounded
      service members.

PMID- 24464237
TI  - A review of telehealth service implementation frameworks.
AB  - Despite the potential of telehealth services to increase the quality and
      accessibility of healthcare, the success rate of such services has been
      disappointing. The purpose of this paper is to find and compare existing
      frameworks for the implementation of telehealth services that can contribute to
      the success rate of future endeavors. After a thorough discussion of these
      frameworks, this paper outlines the development methodologies in terms of
      theoretical background, methodology and validation. Finally, the common themes
      and formats are identified for consideration in future implementation. It was
      confirmed that a holistic implementation approach is needed, which includes
      technology, organizational structures, change management, economic feasibility,
      societal impacts, perceptions, user-friendliness, evaluation and evidence,
      legislation, policy and governance. Furthermore, there is some scope for
      scientifically rigorous framework development and validation approaches. 

PMID- 24464238
TI  - Optimisation of oat milk formulation to obtain fermented derivatives by using
      probiotic Lactobacillus reuteri microorganisms.
AB  - Functional advantages of probiotics combined with interesting composition of oat
      were considered as an alternative to dairy products. In this study, fermentation
      of oat milk with Lactobacillus reuteri and Streptococcus thermophilus was
      analysed to develop a new probiotic product. Central composite design with
      response surface methodology was used to analyse the effect of different factors
      (glucose, fructose, inulin and starters) on the probiotic population in the
      product. Optimised formulation was characterised throughout storage time at 4 C
      in terms of pH, acidity, beta-glucan and oligosaccharides contents, colour and
      rheological behaviour. All formulations studied were adequate to produce
      fermented foods and minimum dose of each factor was considered as optimum. The
      selected formulation allowed starters survival above 10(7)/cfu ml to be
      considered as a functional food and was maintained during the 28 days controlled.
      beta-glucans remained in the final product with a positive effect on viscosity.
      Therefore, a new probiotic non-dairy milk was successfully developed in which
      high probiotic survivals were assured throughout the typical yoghurt-like shelf
      life.

PMID- 24464239
TI  - Probing the conformation and 2D-distribution of pyrene-terminated redox-labeled
      poly(ethylene glycol) chains end-adsorbed on HOPG using cyclic voltammetry and
      atomic force electrochemical microscopy.
AB  - The present paper aims at illustrating how end-attachment of water-soluble
      flexible chains bearing a terminal functional group onto graphene-like surfaces
      has to be carefully tuned to ensure the proper positioning of the functional
      moiety with respect to the anchoring surface. The model experimental system
      considered here consists of a layer of poly(ethylene glycol) (PEG) chains,
      bearing an adsorbing pyrene foot and a ferrocene (Fc) redox functional head, self
      assembled onto highly oriented pyrolytic graphite (HOPG). Cyclic voltammetry is
      used to accurately measure the chain coverage and gain insights into the
      microenvironment experienced by the Fc heads. Molecule-touching atomic force
      electrochemical microscopy (Mt/AFM-SECM) is used to simultaneously probe the
      chain conformation and the position of the Fc heads within the layer, and also to
      map the 2D-distribution of the chains over the surface. This multiscale
      electrochemical approach allows us to show that whereas Fc-PEG-pyrene readily
      self-assembles to form extremely homogeneous layers, the strongly hydrophobic
      nature of graphite planes results in a complex coverage-dependent structure of
      the PEG layer due to the interaction of the ferrocene label with the HOPG
      surface. It is shown that, even though pyrene is known to adsorb particularly
      strongly onto HOPG, the more weakly adsorbing terminal ferrocene can also act as
      the chain anchoring moiety especially at low coverage. However we show that
      beyond a critical coverage value the Fc-PEG-pyrene chains adopt an ideal "foot
      on" end-attached conformation allowing the Fc head to explore a volume away from
      the surface solely limited by the PEG chain elasticity. 

PMID- 24464240
TI  - Elementary school children's cheating behavior and its cognitive correlates.
AB  - Elementary school children's cheating behavior and its cognitive correlates were
      investigated using a guessing game. Children (n=95) between 8 and 12 years of age
      were asked to guess which side of the screen a coin would appear on and received
      rewards based on their self-reported accuracy. Children's cheating behavior was
      measured by examining whether children failed to adhere to the game rules by
      falsely reporting their accuracy. Children's theory-of-mind understanding and
      executive functioning skills were also assessed. The majority of children cheated
      during the guessing game, and cheating behavior decreased with age. Children with
      better working memory and inhibitory control were less likely to cheat. However,
      among the cheaters, those with greater cognitive flexibility use more tactics
      while cheating. Results revealed the unique role that executive functioning plays
      in children's cheating behavior: Like a double-edged sword, executive functioning
      can inhibit children's cheating behavior, on the one hand, while it can promote
      the sophistication of children's cheating tactics, on the other.

PMID- 24464241
TI  - Central nervous system paracoccidioidomycosis in an AIDS patient: case report.
AB  - Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV
      infection have already been reported; however, the central nervous system
      involvement in this coinfection was rarely reported. This paper presents a 35
      year-old Brazilian male AIDS patient who developed pulmonary PCM successfully
      treated with itraconazole. At the antiretroviral therapy starting, he had 32
      CD4(+) T cells baseline count and high viral load levels. After 9 months, he
      presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced
      nodular lesion at computerized tomography and magnetic resonance brain imaging
      and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal
      fluid. At the time, a sixfold increase in CD4(+) T cell count and undetectable
      viral load level were evidenced. The patient received amphotericin B during 1
      year presenting slow but progressive clinical improvement, and he is currently
      asymptomatic and without neurological disabilities. To our knowledge, this is the
      second case report of a patient with neuroparacoccidioidomycosis associated to
      HIV infection.

PMID- 24464242
TI  - External built residential environment characteristics that affect mental health
      of adults.
AB  - External built residential environment characteristics include aspects of
      building design such as types of walls, doors and windows, green spaces, density
      of houses per unit area, and waste disposal facilities. Neighborhoods that are
      characterized by poor quality external built environment can contribute to
      psychosocial stress and increase the likelihood of mental health disorders. This
      study investigated the relationship between characteristics of external built
      residential environment and mental health disorders in selected residences of
      Nakuru Municipality, Kenya. External built residential environment
      characteristics were investigated for 544 residents living in different
      residential areas that were categorized by their socioeconomic status. Medically
      validated interview schedules were used to determine mental health of residents
      in the respective neighborhoods. The relationship between characteristics of the
      external built residential environment and mental health of residents was
      determined by multivariable logistic regression analyses and chi-square tests.
      The results show that walling materials used on buildings, density of dwelling
      units, state of street lighting, types of doors, states of roofs, and states of
      windows are some built external residential environment characteristics that
      affect mental health of adult males and females. Urban residential areas that are
      characterized by poor quality external built environment substantially expose the
      population to daily stressors and inconveniences that increase the likelihood of
      developing mental health disorders. 

PMID- 24464243
TI  - Room-temperature antiferromagnetic memory resistor.
AB  - The bistability of ordered spin states in ferromagnets provides the basis for
      magnetic memory functionality. The latest generation of magnetic random access
      memories rely on an efficient approach in which magnetic fields are replaced by
      electrical means for writing and reading the information in ferromagnets. This
      concept may eventually reduce the sensitivity of ferromagnets to magnetic field
      perturbations to being a weakness for data retention and the ferromagnetic stray
      fields to an obstacle for high-density memory integration. Here we report a room
      temperature bistable antiferromagnetic (AFM) memory that produces negligible
      stray fields and is insensitive to strong magnetic fields. We use a resistor made
      of a FeRh AFM, which orders ferromagnetically roughly 100 K above room
      temperature, and therefore allows us to set different collective directions for
      the Fe moments by applied magnetic field. On cooling to room temperature, AFM
      order sets in with the direction of the AFM moments predetermined by the field
      and moment direction in the high-temperature ferromagnetic state. For electrical
      reading, we use an AFM analogue of the anisotropic magnetoresistance. Our
      microscopic theory modelling confirms that this archetypical spintronic effect,
      discovered more than 150 years ago in ferromagnets, is also present in AFMs. Our
      work demonstrates the feasibility of fabricating room-temperature spintronic
      memories with AFMs, which in turn expands the base of available magnetic
      materials for devices with properties that cannot be achieved with ferromagnets. 

PMID- 24464244
TI  - Thermally driven ratchet motion of a skyrmion microcrystal and topological magnon
      Hall effect.
AB  - Spontaneously emergent chirality is an issue of fundamental importance across the
      natural sciences. It has been argued that a unidirectional (chiral) rotation of a
      mechanical ratchet is forbidden in thermal equilibrium, but becomes possible in
      systems out of equilibrium. Here we report our finding that a topologically
      nontrivial spin texture known as a skyrmion--a particle-like object in which
      spins point in all directions to wrap a sphere--constitutes such a ratchet. By
      means of Lorentz transmission electron microscopy we show that micrometre-sized
      crystals of skyrmions in thin films of Cu2OSeO3 and MnSi exhibit a unidirectional
      rotation motion. Our numerical simulations based on a stochastic Landau-Lifshitz
      Gilbert equation suggest that this rotation is driven solely by thermal
      fluctuations in the presence of a temperature gradient, whereas in thermal
      equilibrium it is forbidden by the Bohr-van Leeuwen theorem. We show that the
      rotational flow of magnons driven by the effective magnetic field of skyrmions
      gives rise to the skyrmion rotation, therefore suggesting that magnons can be
      used to control the motion of these spin textures.

PMID- 24464246
TI  - Intimate Partner and Sexual Violence Research: Scientific Progress, Scientific
      Challenges, and Gender.
AB  - The purpose of this review is to evaluate the current status of scientific
      knowledge on intimate partner violence (IPV) and sexual violence, with a
      particular focus on the measurement of gender patterns. A multimethod analysis of
      estimates for the incidence and prevalence of intimate and sexual aggression
      reveals consistencies across some methodologies and inconsistencies across
      others. In particular, self-report using behavioral checklists such as the
      Revised Conflict Tactics Scales yields results that are very discrepant from
      other research findings. Contrary to some assertions, self-report studies using
      simple checklists do not represent "most data" on intimate violence; there are
      large criminological and public health databases that warrant attention. When
      these sources are considered and placed in the context of other data on violence
      and aggression, a clear pattern of gender asymmetry emerges, with males
      perpetrating more physical and sexual violence than females for virtually every
      form of violence ever studied. Violence research has been hampered by the
      conservative forces that affect most social science research, including peer
      review, grant review, and tenure review processes that discourage methodological
      innovation and reward incremental research studies. We need to focus resources on
      scientific and technological innovation to better understand violent phenomena
      and better serve all those involved in violence. Two examples of self-report
      methods that do not produce gender symmetry are described.

PMID- 24464245
TI  - Electric-field control of magnetic order above room temperature.
AB  - Controlling magnetism by means of electric fields is a key issue for the future
      development of low-power spintronics. Progress has been made in the electrical
      control of magnetic anisotropy, domain structure, spin polarization or critical
      temperatures. However, the ability to turn on and off robust ferromagnetism at
      room temperature and above has remained elusive. Here we use ferroelectricity in
      BaTiO3 crystals to tune the sharp metamagnetic transition temperature of
      epitaxially grown FeRh films and electrically drive a transition between
      antiferromagnetic and ferromagnetic order with only a few volts, just above room
      temperature. The detailed analysis of the data in the light of first-principles
      calculations indicate that the phenomenon is mediated by both strain and field
      effects from the BaTiO3. Our results correspond to a magnetoelectric coupling
      larger than previous reports by at least one order of magnitude and open new
      perspectives for the use of ferroelectrics in magnetic storage and spintronics. 

PMID- 24464248
TI  - Defect-related ferromagnetism in ultrathin metal-free g-C3N4 nanosheets.
AB  - Ultrathin metal-free g-C3N4 nanosheets with intrinsic room temperature
      ferromagnetism were synthesized by heating urea in an airtight container at
      different temperatures. Results indicate that the samples' saturation
      magnetization increases with the carbon defect concentration, revealing its
      carbon defect related ferromagnetism. Moreover, we further confirmed the defect
      induced ferromagnetic nature by ab initio calculations. It is believed that this
      finding highlights a new promising material toward realistic metal-free
      spintronic application. 

PMID- 24464247
TI  - Social withdrawal at 1 year is associated with emotional and behavioural problems
      at 3 and 5 years: the Eden mother-child cohort study.
AB  - The objective of the study was to examine how social withdrawal in infants aged
      12 months predicted emotional and behavioural problems at ages 3 and 5 years. The
      sample included 1,586 infants from the French Eden Mother-Child Cohort Study who
      had a measure of social withdrawal with the Alarm Distress BaBy scale at age 1
      year; among these children, emotional and behavioural difficulties were rated by
      mothers using the Strength and Difficulty Questionnaire (SDQ) at 3 years for
      1,257 (79 %) children and at 5 years for 1,123 (72 %) children. Social withdrawal
      behaviour at age 1 year was significantly associated with the SDQ behavioural
      disorder scale at 3 years, independently of a host of familial and child
      temperament confounders. The association with the relational disorder, prosocial
      and total difficulty scales was close to significance at 3 years after taking
      into account familial and temperament confounders. Social withdrawal
      significantly predicted the three aforementioned scales when measured at 5 years.
      No significant predictivity of the emotional scale and hyperactivity scale was
      detected at any age. This study made with a large longitudinal sample confirms
      the negative effects on development of social withdrawal behaviour, shedding
      light on the unfolding of behavioural disorders and relational difficulties in
      children; this calls for early detection of sustained social withdrawal
      behaviour, as it seems to hamper emotional development.

PMID- 24464249
TI  - Brain tumor senescence might be mediated by downregulation of S-phase kinase
      associated protein 2 via butylidenephthalide leading to decreased cell viability.
AB  - Developing an effective drug for treating human glioblastoma multiform (GBM) has
      been investigated persistently. A pure compound butylidenephthalide (BP),
      isolated from Angelica sinensis, has been shown the activities to arrest the
      growth and initiate apoptosis of GBM in our previous reports. In this study, we
      further demonstrated that BP treatment accelerates the cell senescence in a dose
      dependent manner in vitro and in vivo. S-phase kinase-associated protein 2
      (Skp2), a proto-oncogene, is generally upregulated in cancer. We found that it
      was downregulated in BP-treated GBM cells. The downregulation of Skp2 is parallel
      with increasing p16 and p21 expression which causes G0/G1 arrest and tumor cell
      senescence. We also found that restoring the Skp2 protein level by exogenous
      overexpression prevents the BP-induced cell senescence. Therefore, the linkage
      between cell senescence and Skp2 expression is strengthened. Promoter binding
      analysis further detailed that the BP-mediated SP1 reduction might involve in the
      Skp2 downregulation. In summary, these results emphasize that BP-triggered
      senescence in GBM cells is highly associated with its control on Skp2 regulation.

PMID- 24464250
TI  - Lack of association between IL-4 -588C>T polymorphism and NHL susceptibility.
AB  - The relationship of non-Hodgkin's lymphoma (NHL) with the presence of interleukin
      4 genetic polymorphism -588C>T has been reported with inconsistent results. The
      objective of this study was to quantitatively evaluate the association between 
      588C>T polymorphism and NHL susceptibility. Two investigators independently
      searched Medline and the Cochrane Library up to September 20, 2013. Pooled odds
      ratio and 95% confidence interval were calculated using a fixed or random effects
      model. Statistical analysis was performed with Review Manage 5.0 and Stata 11. Of
      the six case-control studies selected for this meta-analysis, a total of 1,909
      NHL cases and 1,834 controls were included. The combined results based on all
      studies suggested that -588C>T was not associated with NHL risk under all genetic
      models. When stratifying for race, no noteworthy associations were observed in
      mixed populations or Caucasians. This meta-analysis suggests that IL-4 -588C>T
      polymorphism might not be a risk factor for NHL risk. However, further well
      designed studies are required to confirm our findings.

PMID- 24464251
TI  - Peer victimization and child physical health: the moderating role of pessimism.
AB  - OBJECTIVE: Involvement in peer victimization has been associated with numerous
      negative consequences, including poor physical health. The purpose of this study
      is to improve on previous research evaluating the victimization-health
      relationship by examining the health (i.e., health-related quality of life
      [HRQoL], medical service utilization) of both victims and aggressors and
      examining individual variation in this relationship through the moderating effect
      of pessimism. METHOD: The sample included 125 ethnically diverse youth aged 8-11
      years recruited from a low-income medical practice. Child-report of involvement
      in peer victimization and pessimism was assessed along with parent-report of
      HRQoL. 2-year medical service utilization was extracted from medical records.
      RESULTS: Although not all hypotheses were supported, victims and aggressors were
      found to be at increased risk for certain poor health outcomes, which were
      exacerbated by high levels of pessimism. CONCLUSION: Findings expand on research
      into peer victimization and health and provide important implications for
      identification, prevention, and intervention strategies with at-risk youth.

PMID- 24464252
TI  - The search for causal inferences: using propensity scores post hoc to reduce
      estimation error with nonexperimental research.
AB  - While experimental designs are regarded as the gold standard for establishing
      causal relationships, such designs are usually impractical owing to common
      methodological limitations. The objective of this article is to illustrate how
      propensity score matching (PSM) and using propensity scores (PS) as a covariate
      are viable alternatives to reduce estimation error when experimental designs
      cannot be implemented. To mimic common pediatric research practices, data from
      140 simulated participants were used to resemble an experimental and
      nonexperimental design that assessed the effect of treatment status on
      participant weight loss for diabetes. Pretreatment participant characteristics
      (age, gender, physical activity, etc.) were then used to generate PS for use in
      the various statistical approaches. Results demonstrate how PSM and using the PS
      as a covariate can be used to reduce estimation error and improve statistical
      inferences. References for issues related to the implementation of these
      procedures are provided to assist researchers. 

PMID- 24464253
TI  - Alcohol induced disorders.

PMID- 24464254
TI  - [Genetic analyses as basis for a personalized medicine in patients with coronary
      artery disease].
AB  - Knowledge about the etiology of coronary artery disease (CAD) entered new
      dimensions using genome-wide association studies. The current situation is that
      46 chromosomal loci have been identified to be associated with CAD with genome
      wide significance, i.e. p<5*10(-8), in Western Europeans. As the individual DNA
      sequence remains unchanged after fertilization, the risk variants cannot occur
      due to confounders, such as secondary disease processes. Thus, it can be proposed
      that these variants are directly affecting a primary and thereby causal
      pathophysiological process in CAD. Interestingly, only 20% of the effects
      mediated by the identified loci can be explained by the influence of traditional
      risk factors. This implies that yet unknown mechanisms and, as a consequence, new
      therapeutic targets play an important role in the pathophysiology of CAD.
      However, the high allele frequency of risk loci was also surprising. In the
      diploid chromosome set Western European individuals carry on average 30-50 risk
      variants at the 46 loci. Considering this, every individual in the population
      carries a larger or smaller genetic predisposition for CAD. On the other hand it
      is remarkable that many risk allele carriers seem to be able to compensate the
      genetic risk: even in old age not everyone suffers from CAD. This indicates yet
      unknown gene-gene and gene-environment interactions and limits the current
      possibilities in individual risk prediction. 

PMID- 24464255
TI  - Anticoagulant therapy in oncologic patients undergoing venous stenting for
      superior vena cava syndrome and other interventional procedures.

PMID- 24464256
TI  - Cerebral hyperperfusion syndrome after endovascular reconstruction of carotid
      artery in high-flow carotid-jugular fistula.
AB  - We describe the occurrence of cerebral hyperperfusion syndrome (CHS) in a case of
      long-standing carotid-jugular fistula (CJF) treated by endovascular
      reconstruction of the carotid artery. A 43-year-old male with a high-flow CJF
      between the internal carotid artery (ICA) and internal jugular vein underwent
      endovascular reconstruction of the carotid artery using a stent graft. After
      treatment, the patient developed CHS. The patient succumbed to a large
      intracranial bleed in the left external capsule and parietal lobe on the fifth
      postoperative day. CHS following endovascular reconstruction of carotid artery is
      rare. We present the first reported case of CHS following endovascular
      reconstruction of ICA. A review of literature for patients treated by
      endovascular rerouting of blood flow to the cerebral parenchyma associated with
      hyperperfusion syndrome has been performed.

PMID- 24464257
TI  - Intra-arterial ultra low iodine CT angiography of renal transplant arteries.
AB  - PURPOSE: This study was designed to evaluate the technical feasibility and the
      image quality of intra-arterial 320-row CT angiography (ia-CTA) in the detection
      of transplant renal artery stenosis (TRAS) using a very low dose of contrast
      agent. METHODS: Evaluation of ia-CTA using a 4F catheter in ten patients with
      impaired renal transplant function and suspected TRAS. Average amount of contrast
      agent applied was 10 +/- 3.7 ml standard deviation (SD). Patient serum creatinine
      levels had been monitored for 72 h. TRAS was detected and graded (1: less than 20
      %; 2: 20-49 %; 3: 50-74 %; 4: 75-99 %; 5: total occlusion) and presence of
      kinking was recorded. Attenuation and vessel delineation were parameters for
      image quality analysis of the renal arterial supply, divided into four segments.
      Subjective image quality. RESULTS: Ia-CTA of the renal transplant was technically
      successful in all patients, revealing relevant stenoses in 7 of 10 patients.
      Serum creatinine levels before and after ia-CTA were 2.71 +/- 1.46 and 2.56 +/-
      1.39 mg/dl, respectively. None of the patients developed signs of contrast
      induced nephropathy within 72 h. Subjective image quality was excellent in all
      four segments, rated by two separate readers. No segment was found to be
      nondiagnostic. Mean attenuation values in the arterial segments ranged between
      754 and 987 Hounsfield units. CONCLUSIONS: Wide detector ia-CTA for the diagnosis
      of TRAS is feasible using very low doses of contrast agent and results in high
      image quality.

PMID- 24464258
TI  - Is the adjuvant albendazole treatment really needed with PAIR in the management
      of liver hydatid cysts? A prospective, randomized trial with short-term follow-up
      results.
AB  - OBJECTIVE: The purpose of this study was to determine the safety and efficacy of
      adjuvant albendazole medication in percutaneous liver hydatid cyst treatment with
      puncture, aspiration, injection, and reaspiration (PAIR) method. METHODS: Between
      November 2007 and May 2011, total of 39 patients with newly diagnosed liver
      hydatid cyst (total of 77 cysts) were prospectively randomized and enrolled in 3
      groups. In the first group, cysts (n = 14) were treated with PAIR without
      albendazole. In the second (n = 16) and third groups (n = 47), cysts were treated
      with PAIR with albendazole 1 week before and 1 month after the procedure, with
      albendazole 1 week before and 3 months after the procedure respectively. RESULTS:
      Technical and clinical success rates were 100 and 96.1% respectively. In 3 of 77
      cysts (3.9%), findings of recurrence were detected on US imaging. All recurrent
      cysts were in group 1 and recurrence rates in this group were statistically
      different from cysts of second and third groups (p = 0.005). Side effects of
      albendazole were detected in 7 of 29 patients (24.1%), and no statistically
      significant difference was observed between the second (15.3%) and third (38.4%)
      groups (p = 0.378). CONCLUSIONS: Use of albendazole medication as an adjuvant to
      percutaneous treatment of liver hydatid cyst decreases the recurrence rate.
      Although there is no statistically significant difference between groups 2 and 3
      in terms of efficacy and recurrence rate, patients in group 3 had a higher rate
      of side effect. Therefore, we conclude that albendazole treatment 1 week before
      and 1 month after PAIR treatment is sufficient to reduce/prevent recurrences.

PMID- 24464259
TI  - Treatment outcomes of transcatheter arterial chemoembolization for hepatocellular
      carcinoma that invades hepatic vein or inferior vena cava.
AB  - PURPOSE: We aimed to elucidate the treatment outcomes of transcatheter arterial
      chemoembolization (TACE) and survival-associated factors in hepatocellular
      carcinoma (HCC) patients with hepatic vein (HV) and/or inferior vena cava (IVC)
      invasion. METHODS: The subjects were consecutively enrolled, newly diagnosed HCC
      patients with HV/IVC invasion who underwent TACE (n = 62) at the Seoul National
      University Bundang Hospital from May 2003 to October 2012. Clinical
      characteristics, treatment responses, overall survival, and survival-related
      factors were analyzed. RESULTS: The mean subject age was 56.6 years, 82.3% were
      hepatitis B surface antigen-positive, and 76.2% were classified as Child-Pugh
      class A. The tumor volume was >=50% of the liver in 64.5% of patients, and 79,
      41.9, and 9.7% of patients had accompanying portal vein, IVC, and right atrial
      invasion, respectively. TACE response rates for primary tumors and tumor thrombi
      in HV or IVC were 55.6 and 13%, respectively. Median overall survival was 10.9
      months (range 0.1-23.0 months). Multivariate analysis showed that Child-Pugh
      class A (hazard ratio [HR] = 0.31; 95% confidence interval [CI] 0.14-0.72; p =
      0.007), tumor volume <50% of liver (HR = 0.31; 95% CI 0.11-0.83; p = 0.019),
      alpha-fetoprotein (AFP) response (HR = 0.28; 95% CI 0.11-0.69; p = 0.006), and
      tumor thrombi treatment response (HR = 0.09; 95% CI 0.01-0.77; p = 0.027) were
      independent survival-related factors. CONCLUSIONS: TACE seems effective for HCC
      with HV/IVC invasion, especially in patients with preserved hepatic function, a
      treatment response for tumor thrombi, and an AFP response.

PMID- 24464260
TI  - Wireless blood pressure monitoring with a novel implantable device: long-term in
      vivo results.
AB  - PURPOSE: Devices constantly tracking the blood pressure (BP) of hypertensive
      patients are highly desired to facilitate effective patient management and to
      reduce hospitalization. We report on experiences gathered in a pilot study that
      was designed to evaluate the prototype of a newly developed, minimally invasive
      implantable sensor system for long-term BP monitoring. METHODS: The device was
      implanted in the femoral artery (FA) of 12 sheep via standard FA catheterization
      under fluoroscopic control. Accuracy of the recorded blood pressure was
      determined by comparison with a reference catheter, which was positioned in the
      contralateral FA immediately after implantation. Regular follow-up included
      angiography, computed tomography (CT), and control of functionality and position
      of the BP sensor. Animals were euthanized after 6 months. FA segments with in
      situ pressure sensor underwent macroscopic and histopathologic examinations.
      RESULTS: All implantations of the novel sensor device in the FA were successful
      and uneventful. High-quality BP recordings were documented. Bland-Altman plots
      indicate very good agreement. Comparison with measurements taken from the
      reference sensor revealed mean differences and standard deviations of -0.56 +/-
      0.85, 0.29 +/- 1.44, and 0.85 +/- 2.27 mmHg (diastolic, systolic, and pulse
      pressure, respectively) after exclusion of one outlier. CT uncovered deficiencies
      in cable stability that were addressed in a redesign. No thrombus formation,
      necrosis, or apoptosis were detected. CONCLUSIONS: The pilot study proved the
      technical feasibility of wireless BP measurement in the FA via a novel miniature
      sensor device.

PMID- 24464261
TI  - Percutaneous cryoablation of symptomatic abdominal scar endometrioma: initial
      reports.
AB  - PURPOSE: The purpose of this preliminary study was to report the short-term local
      control of percutaneous image-guided cryoablation of localized symptomatic
      abdominal scar endometrioma. METHODS: Four consecutive patients (mean age 34.5
      years) with a total of ten lesions were included, with mean preoperative pain of
      7 (range 5-9) on the visual analog scale. Cryoablation was performed in a single
      session under general anesthesia. RESULTS: Postoperative superficial edema
      disappeared within 2 weeks for all patients. No severe complications (>grade 2
      according to the CTCAE classification) were reported. Mean postoperative pain was
      1.7 at 6 months (range 0-5) and magnetic resonance imaging demonstrated a
      significant volume decrease for all patients (range 72.2-100%; p = 0.028).
      CONCLUSIONS: Percutaneous cryoablation shows promising local control in patients
      with symptomatic abdominal wall endometriosis.

PMID- 24464262
TI  - Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe
      epilepsy.
AB  - Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from
      astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron
      population with metabolic intermediates to meet energy requirements under
      conditions of increased demand. Disruption of this astroglial-neuron metabolic
      coupling pathway may contribute to epileptogenesis. We measured MCT4 expression
      in temporal lobe epileptic foci excised from patients with intractable epilepsy
      and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy
      (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients
      compared with controls, due at least partially to MCT4 promoter methylation.
      Expression of MCT4 also decreased progressively in pilocarpine-treated rats from
      12 h to 14 days post-administration. Underexpression of MCT4 in cultured
      astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of
      astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1)
      expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal
      hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply
      of metabolic intermediates and by allowing accumulation of extracellular
      glutamate.

PMID- 24464265
TI  - Climatic controls on hurricane patterns: a 1200-y near-annual record from
      Lighthouse Reef, Belize.
AB  - Tropical cyclones (TCs) are powerful agents of destruction, and understanding
      climatic controls on TC patterns is of great importance. Over timescales of
      seasons to several decades, relationships among TC track, frequency, intensity
      and basin-scale climate changes are well documented by instrumental records. Over
      centuries to millennia, climate-shift influence on TC regimes remains poorly
      constrained. To better understand these relationships, records from multiple
      locations of TC strikes spanning millennia with high temporal resolution are
      required, but such records are rare. Here we report on a highly detailed
      sedimentary proxy record of paleo-TC strikes from the Blue Hole of Lighthouse
      Reef, Belize. Our findings provide an important addition to other high-resolution
      records, which collectively demonstrate that shifts between active and inactive
      TC regimes have occurred contemporaneously with shifts hemispheric-scale oceanic
      and atmospheric circulation patterns such as MDR SSTs and NAO mode, rather than
      with changes in local climate phenomena as has previously been suggested. 

PMID- 24464263
TI  - Crosstalk between insulin and Toll-like receptor signaling pathways in the
      central nervous system.
AB  - Neuroinflammation is known as a key player in a variety of neurodegenerative
      and/or neurological diseases. Brain Toll-like receptors (TLRs) are leading
      elements in the initiation and progression of neuroinflammation and the
      development of different neuronal diseases. Furthermore, TLR activation is one of
      the most important elements in the induction of insulin resistance in different
      organs such as the central nervous system. Involvement of insulin signaling
      dysregulation and insulin resistance are also shown to contribute to the
      pathology of neurological diseases. Considering the important roles of TLRs in
      neuroinflammation and central insulin resistance and the effects of these
      processes in the initiation and progression of neurodegenerative and neurological
      diseases, here we are going to review current knowledge about the potential
      crosstalk between TLRs and insulin signaling pathways in neuroinflammatory
      disorders of the central nervous system. 

PMID- 24464264
TI  - Distribution of secretory phospholipase A2 XIIA in the brain and its role in
      lipid metabolism and cognition.
AB  - Phospholipases A(2) (PLA(2)) catalyze the hydrolysis of membrane phospholipids to
      produce free fatty acids and lysophospholipids, which have important functions in
      cell signaling. The present study elucidated differential expression of PLA(2)
      isoforms in the rat cortex by quantitative reverse transcription PCR and
      demonstrated that sPLA(2)-XIIA had greater messenger RNA expression than iPLA(2)
      VI or cPLA(2)-IVA in different brain regions, or compared to other sPLA(2)
      isoforms in the prefrontal cortex (PFC) and hippocampus. Western blots identified
      a 24-kDa band in different regions of the adult brain, and high levels of sPLA(2)
      XIIA protein expression were detected in the PFC, striatum, and thalamus.
      Electron microscopy showed that sPLA(2)-XIIA is present in axon terminals and
      dendrites. Injection of antisense oligonucleotide to sPLA(2)-XIIA in the PFC and
      lipidomic analysis showed increase in phospholipid but decrease in
      lysophospholipid species consistent with decreased catalytic activity of the
      enzyme, changes in arachidonic acid release, and alterations in sphingolipids.
      sPLA(2)-XIIA knockdown also resulted in shorter latency timings in the passive
      avoidance test, and higher number of errors in the attention set-shifting task,
      indicating deficits in working memory and attention. Together, the results show
      an important role of sPLA(2)-XIIA in lipid metabolism, prefrontal cortical
      function, and cognition.

PMID- 24464266
TI  - Phase II trial of vorinostat in advanced melanoma.
AB  - INTRODUCTION: Vorinostat is a small molecule inhibitor of class I and II histone
      deacetylases with preclinical activity in melanoma. METHODS: We evaluated 32
      patients with advanced primary cutaneous or ocular melanoma in a multi
      institutional setting (PMH Phase II Consortium) with continuous daily oral
      vorinostat 400 mg. The primary endpoint was response rate by RECIST, with time to
      progression as a secondary endpoint. The study was designed to distinguish a
      response rate of 20 % from a RR of 5 % and to distinguish a 2 month median
      progression-free survival (PFS), from one of 3.1 months. The study proceeded to
      stage 2 following 2 of 16 responses.. We also assessed VEGF, FGF levels, P52
      polymorphisms and chromatin-associated proteins as potential biomarkers. RESULTS:
      Therapy was associated with significant side effects, including fatigue, nausea,
      lymphopenia, and hyperglycemia. Eleven patients experienced at least one grade 3
      or higher adverse event. There were two confirmed PRs in patients with cutaneous
      melanoma. Sixteen patients had stable disease and 14 patients had progressive
      disease for best response. In addition, two patients with cutaneous melanoma
      scored as stable disease had early unconfirmed partial responses with subsequent
      progression. Patients with stable disease or partial response (n = 18) had a
      median progression free survival of 5 months. (range 2-12 months). CONCLUSIONS:
      Vorinostat demonstrated some early responses and a high proportion of patients
      with stable disease, but did not meet its primary endpoint of response. Different
      schedules of this agent with BRAF mutation status and markers of histone
      acetylation could be explored in melanoma.

PMID- 24464267
TI  - Cross-sectional associations between violent video and computer game playing and
      weapon carrying in a national cohort of children.
AB  - Data were collected from 9 to 18 year olds surveyed nationally in a three-wave
      longitudinal survey. The population-average (generalized estimating equation,
      GEE) odds of carrying a weapon to school in the last month were estimated as a
      function of past-year exposure to violent content in video, computer, and
      Internet games, as well as peer aggression and biological sex. The sample
      included youth who were at risk for both the exposure (i.e., game play) and the
      outcome (i.e., who attended public or private school). 3,397 observations from
      1,489 youth were included in analyses. 1.4% of youth reported carrying a weapon
      to school in the last month and 69% reported that at least some of the games they
      played depicted violence. After adjusting for other potentially influential
      characteristics (e.g., aggressive behavior), playing at least some violent games
      in the past year was associated with a fourfold increase in odds of also
      reporting carrying a weapon to school in the last month. Although youth who
      reported frequent and intense peer victimization in the past year were more
      likely to report carrying a weapon to school in the last month, this relation was
      explained by other influential characteristics. Consistent with the predictions
      of social-cognitive, observational learning theory, this study supports the
      hypothesis that carrying weapons to school is associated with violent game play.
      As one of the first studies of its kind, findings should be interpreted
      cautiously and need to be replicated.

PMID- 24464268
TI  - Improvement of HIV fusion inhibitor C34 efficacy by membrane anchoring and
      enhanced exposure.
AB  - OBJECTIVES: The aim of the present work was to evaluate the interaction of two
      new HIV fusion inhibitors {HIVP3 [C34-polyethylene glycol (PEG)4-cholesterol] and
      HIVP4 [(C34-PEG4)2-cholesterol]} with membrane model systems and human blood
      cells in order to clarify where and how the fusion inhibitors locate, allowing us
      to understand their mechanism of action at the molecular level, and which
      strategies may be followed to increase efficacy. METHODS: Lipid vesicles with
      defined compositions were used for peptide partition and localization studies,
      based on the intrinsic fluorescence of HIVP3 and HIVP4. Lipid monolayers were
      employed in surface pressure studies. Finally, human erythrocytes and peripheral
      blood mononuclear cells (PBMCs) isolated from blood samples were used in dipole
      potential assays. RESULTS: Membrane partition, dipole potential and surface
      pressure assays indicate that the new fusion inhibitors interact preferentially
      with cholesterol-rich liquid-ordered membranes, mimicking biological membrane
      microdomains known as lipid rafts. HIVP3 and HIVP4 are able to interact with
      human erythrocytes and PBMCs to a similar degree as a previously described
      simpler drug with monomeric C34 and lacking the PEG spacer, C34-cholesterol.
      However, the pocket-binding domain (PBD) of both HIVP3 and HIVP4 is more exposed
      to the aqueous environment than in C34-cholesterol. CONCLUSIONS: The present data
      allow us to conclude that more efficient blocking of HIV entry results from the
      synergism between the membranotropic behaviour and the enhanced exposure of the
      PBD.

PMID- 24464269
TI  - Effect of crystallinity on electrostatic charging in dry powder inhaler
      formulations.
AB  - PURPOSE: This study aimed to characterize inherent charge generated by micron
      sized drug-only formulations of amorphous and crystalline salbutamol sulfate
      (SS). METHODS: Amorphous SS was produced by spray-drying whilst crystalline SS
      was produced by conditioning spray-dried SS with supercritical CO2 and menthol.
      Electrostatic charge of the powders was characterized in two ways. Firstly, the
      charge profile of the aerosols dispersed from an Aerolizer(r) was measured using
      a modified Electrostatic Low Pressure Impactor (ELPITM). Secondly, the net charge
      of the bulk powders generated from tumbling in containers composed of different
      materials (polyethylene, polyvinyl chloride, Teflon, nylon and stainless steel)
      was measured by a Faraday pail. RESULTS: Following aerosolization, crystalline SS
      appeared to show more consistent charging and mass deposition than amorphous SS.
      In the tumbling experiment crystalline SS had a significant correlation between
      net charge and work function, which was absent in amorphous SS. This may be due
      to the long-range crystal packing which was reflected as more predictable
      charging. In addition, the polarity of charging was attributed to the arrangement
      of SS molecules in the crystal lattice. CONCLUSIONS: The effect of crystallinity
      on the electrostatic charge behavior of inhalable micron-sized spherical drug
      particles with well-defined particle size distribution was investigated for the
      first time. The knowledge gained may assist in the development of optimized
      inhaled pharmaceutical products.

PMID- 24464272
TI  - Margin width is not predictive of residual disease on re-excision in breast
      conserving therapy.

PMID- 24464270
TI  - Assessment of physical stability of an antibody drug conjugate by higher order
      structure analysis: impact of thiol- maleimide chemistry.
AB  - PURPOSE: To provide a systematic biophysical approach towards a better
      understanding of impact of conjugation chemistry on higher order structure and
      physical stability of an antibody drug conjugate (ADC). METHODS: ADC was prepared
      using thiol-maleimide chemistry. Physical stabilities of ADC and its parent IgG1
      mAb were compared using calorimetric, spectroscopic and molecular modeling
      techniques. RESULTS: ADC and mAb respond differently to thermal stress. Both the
      melting temperatures and heat capacities are substantially lower for the ADC.
      Spectroscopic experiments show that ADC and mAb have similar secondary and
      tertiary structures, but these are more easily destabilized by thermal stress on
      the ADC indicating reduced conformational stability. Molecular modeling
      calculations suggest a substantial decrease in the conformational energy of the
      mAb upon conjugation. The local surface around the conjugation sites also becomes
      more hydrophobic in the ADC, explaining the lower colloidal stability and greater
      tendency of the ADC to aggregate. CONCLUSIONS: Computational and biophysical
      analyses of an ADC and its parent mAb have provided insights into impact of
      conjugation on physical stability and pinpointed reasons behind lower structural
      stability and increased aggregation propensity of the ADC. This knowledge can be
      used to design appropriate formulations to stabilize the ADC.

PMID- 24464271
TI  - One mouse, one pharmacokinetic profile: quantitative whole blood serial sampling
      for biotherapeutics.
AB  - PURPOSE: The purpose of this study was to validate the approach of serial
      sampling from one mouse through ligand binding assay (LBA) quantification of
      dosed biotherapeutic in diluted whole blood to derive a pharmacokinetic (PK)
      profile. METHODS: This investigation compared PK parameters obtained using serial
      and composite sampling methods following administration of human IgG monoclonal
      antibody. The serial sampling technique was established by collecting 10 MUL of
      blood via tail vein at each time point following drug administration. Blood was
      immediately diluted into buffer followed by analyte quantitation using Gyrolab to
      derive plasma concentrations. Additional studies were conducted to understand
      matrix and sampling site effects on drug concentrations. RESULTS: The drug
      concentration profiles, irrespective of biological matrix, and PK parameters
      using both sampling methods were not significantly different. There were no
      sampling site effects on drug concentration measurements except that
      concentrations were slightly lower in sodium citrated plasma than other matrices.
      CONCLUSIONS: We recommend the application of mouse serial sampling, particularly
      with limiting drug supply or specialized animal models. Overall the efficiencies
      gained by serial sampling were 40-80% savings in study cost, animal usage, study
      length and drug conservation while inter-subject variability across PK parameters
      was less than 30%.

PMID- 24464273
TI  - Acaricidal activity of petroleum ether extracts from Eupatorium adenophorum
      against the ectoparasitic cattle mite, Chorioptes texanus.
AB  - In this study, we evaluated the acaricidal efficacy of extracts obtained from the
      plant Eupatorium adenophorum against the common cattle mite Chorioptes texanus.
      The results showed that 95% ethanol extracts at concentrations of 1.0, 0.5, and
      0.25 g/mL (w/v) were highly toxic to C. texanus in vitro, killing 100% of mites
      in 4 h. Similarly, petroleum ether extracts of E. adenophorum resulted in between
      80 and 100% mortality of mites in vitro at concentrations of 0.1, 0.05, and 0.025
      mL/mL (v/v) within 4 h. In clinical trials, all infected individuals completely
      recovered after two treatments administered at 7-day intervals and remained
      disease-free at 60 days posttreatment. The clinical effect of treatment with E.
      adenophorum petroleum ether extracts was similar to that of treatment with the
      acaricide fenvalerate. These results indicated that E. adenophorum contains novel
      potential acaricidal compounds that can effectively control mites in livestock.

PMID- 24464275
TI  - Supramolecular photochemistry of drugs in biomolecular environments.
AB  - In this tutorial review we illustrate how the interaction of photoactive
      drugs/potential drugs with proteins or DNA in supramolecular complexes can
      determine the course of the reactions initiated by the drug absorbed photons,
      evidencing the mechanistic differences with respect to the solution conditions.
      We focus on photoprocesses, independent of oxygen, that lead to chemical
      modification of the biomolecules, with formation of new covalent bonds or
      cleavage of existing bonds. Representative systems are mainly selected from the
      literature of the last decade. The photoreactivity of some aryl propionic acids,
      (fluoro)quinolones, furocoumarins, metal coordination complexes, quinine-like
      compounds, naphthaleneimides and pyrenyl-peptides with proteins or DNA is
      discussed. The use of light for biomolecule photomodification, historically
      relevant to biological photosensitization processes and some forms of
      photochemotherapy, is nowadays becoming more and more important in the
      development of innovative methods in nanomedicine and biotechnology. 

PMID- 24464274
TI  - Occurrence of Hysterothylacium and Anisakis nematodes (Ascaridida: Ascaridoidea)
      in the tanaka's snailfish Liparis tanakae (Gilbert & Burke) (Scorpaeniformes:
      Liparidae).
AB  - The tanaka's snailfish Liparis tanakae (Gilbert & Burke) (Scorpaeniformes:
      Liparidae) is an economically important marine fish species in China. However,
      the helminth parasites of this fish are still poorly known. During a
      helminthological survey of Chinese marine fishes from 2011 to 2012, we revealed
      that L. tanakae was heavily infected with third-stage larvae and adults of
      ascaridoid nematodes (total prevalence 100% and mean intensity 82.3 nematodes per
      fish). Four species of third-stage larvae Hysterothylacium liparis Li, Xu &
      Zhang, 2007, H. aduncum (Rudolphi, 1802), Hysterothylacium fabri (Rudolphi,
      1819), and Anisakis pegreffii (Campana-Rouget & Biocca, 1955) and a single
      species of adults H. liparis were differentiated and identified by morphological
      and molecular methods. The detailed morphology of the four species of third-stage
      larvae was also studied using light microscopy and scanning electron microscopy.
      The morphological and molecular characterization of the third-stage larvae of H.
      liparis was reported. Liparis tanakae represents a new host record for A.
      pegreffii and H. fabri. In addition, a new name, Hysterothylacium zhoushanense
      nom. nov. was also given to Hysterothylacium zhoushanensis Li, Liu & Zhang, 2012
      to make the latinized specific epithet agree with this neuter generic name.

PMID- 24464276
TI  - Facilely and efficiently tuning metal-organic nanostructures of a charge-transfer
      complex based on a water controlled nanoreaction and the chemistry of 7,7,8,8
      tetracyanoquinodimethane (TCNQ).
AB  - Metal-organic charge-transfer complexes based on 7,7,8,8-tetracyanoquinodimethane
      (TCNQ) have received considerable attention because of their unique solid-state
      physical properties for potential applications in nanoscale opto-electronic
      devices. To address the challenge in preparing novel metal-TCNQ (MTCNQ)
      nanostructures, here we introduce a facile and efficient way for synthesizing
      MTCNQ, taking Ni[TCNQ]2(H2O)2 as an example. By finely tuning the amount of water
      added into TCNQ solution, well-ordered and large-scale patterns of
      Ni[TCNQ]2(H2O)2 were successfully obtained in a controllable manner. This facile
      method will not only be beneficial for the tailored preparation of nanoscale
      MTCNQ complexes, but also enrich the chemistry of TCNQ. 

PMID- 24464277
TI  - Converting an odds ratio to a range of plausible relative risks for better
      communication of research findings.

PMID- 24464278
TI  - NHS payments should focus on value, not single episodes of care, conference
      hears.

PMID- 24464279
TI  - US newspapers favor weaker studies, researchers say.

PMID- 24464280
TI  - Cabinet Office approval should be required for severance payments that involve
      whistleblowers, MPs say.

PMID- 24464281
TI  - Estimated glomerular filtration rate.

PMID- 24464282
TI  - Middle aged medicine.

PMID- 24464283
TI  - Patient engagement and shared decision-making.

PMID- 24464284
TI  - Capsule commentary on Davis et al., Improving mammography screening among the
      medically underserved.

PMID- 24464285
TI  - Population pharmacokinetics and prediction of dopamine D2 receptor occupancy
      after multiple doses of RBP-7000, a new sustained-release formulation of
      risperidone, in schizophrenia patients on stable oral risperidone treatment.
AB  - BACKGROUND AND OBJECTIVES: RBP-7000 is a long-acting formulation of risperidone
      administered once monthly via subcutaneous (SC) injections for the treatment of
      schizophrenia. The objectives of the present study were to characterize the
      pharmacokinetics of RBP-7000 after multiple doses in schizophrenic patients on
      stable oral risperidone therapy and to evaluate the switch between oral
      risperidone and SC injections of RBP-7000. METHODS: Data were collected in a
      phase IIa, open-label, multiple-ascending-dose study where 45 patients clinically
      stabilized on oral risperidone (2, 3 or 4 mg/day) were switched to receive 60, 90
      or 120 mg/month SC injections of RBP-7000, respectively. Patients were thereafter
      switched back to oral risperidone. An integrated population pharmacokinetic model
      describing simultaneously risperidone and 9-hydroxyrisperidone after risperidone
      oral intake and RBP-7000 administration was developed in NON-MEM using 5,232
      quantifiable plasma concentrations. Predictions of dopamine D2 receptor occupancy
      were derived using a previously published model. RESULTS: A two-compartment model
      with first-order absorption was selected for oral risperidone, while a three
      compartment model with first-order absorption and a transit compartment
      absorption model was selected for RBP-7000. Body mass index was identified as a
      significant covariate affecting the initial absorption of risperidone following
      RBP-7000 injection. Steady state was reached after the second or third RBP-7000
      injection but plasma concentrations close to steady-state values were obtained
      right after the first injection when switching from oral risperidone therapy.
      Predicted dopamine D2 receptor occupancy after repeated doses of 90 and 120 mg
      showed less fluctuation than after oral risperidone with acceptable ranges for
      clinical efficacy and a potentially safer profile with respect to extrapyramidal
      side effects. CONCLUSION: This analysis provided additional insight into the
      pharmacokinetics of RBP-7000 and for the comparison with oral risperidone
      treatment. The established model was used to support the design of a planned
      phase III study.

PMID- 24464286
TI  - Epigenome-wide association studies without the need for cell-type composition.
AB  - In epigenome-wide association studies, cell-type composition often differs
      between cases and controls, yielding associations that simply tag cell type
      rather than reveal fundamental biology. Current solutions require actual or
      estimated cell-type composition--information not easily obtainable for many
      samples of interest. We propose a method, FaST-LMM-EWASher, that automatically
      corrects for cell-type composition without the need for explicit knowledge of it,
      and then validate our method by comparison with the state-of-the-art approach.
      Corresponding software is available from http://www.microsoft.com/science/.

PMID- 24464287
TI  - Similarity network fusion for aggregating data types on a genomic scale.
AB  - Recent technologies have made it cost-effective to collect diverse types of
      genome-wide data. Computational methods are needed to combine these data to
      create a comprehensive view of a given disease or a biological process.
      Similarity network fusion (SNF) solves this problem by constructing networks of
      samples (e.g., patients) for each available data type and then efficiently fusing
      these into one network that represents the full spectrum of underlying data. For
      example, to create a comprehensive view of a disease given a cohort of patients,
      SNF computes and fuses patient similarity networks obtained from each of their
      data types separately, taking advantage of the complementarity in the data. We
      used SNF to combine mRNA expression, DNA methylation and microRNA (miRNA)
      expression data for five cancer data sets. SNF substantially outperforms single
      data type analysis and established integrative approaches when identifying cancer
      subtypes and is effective for predicting survival. 

PMID- 24464288
TI  - Correlative super-resolution fluorescence and metal-replica transmission electron
      microscopy.
AB  - We combine super-resolution localization fluorescence microscopy with
      transmission electron microscopy of metal replicas to locate proteins on the
      landscape of the cellular plasma membrane at the nanoscale. We validate robust
      correlation on the scale of 20 nm by imaging endogenous clathrin (in two and
      three dimensions) and apply the method to find the previously unknown three
      dimensional position of the endocytic protein epsin on clathrin-coated structures
      at the plasma membrane. 

PMID- 24464289
TI  - Cloning, expression and characterization of a novel cold-active and halophilic
      xylanase from Zunongwangia profunda.
AB  - A new xylanase gene (xynA) from the marine microorganism Zunongwangia profunda
      was identified to encode 374 amino acid residues. Its product (XynA) showed the
      highest identity (42.78%) with a xylanase from Bacillus sp. SN5 among the
      characterized xylanases. XynA exhibited the highest activity at pH 6.5 and 30 
      degrees C, retaining 23 and 38% of the optimal activity at 0 and 5  degrees C,
      respectively. XynA was not only cold active, but also halophilic, and both its
      activity and thermostability could be significantly increased by NaCl, showing
      the highest activity (180% of the activity) at 3 M NaCl and retaining nearly 100%
      activity at 5 M NaCl, compared to the absence of NaCl. In the presence of 3 M
      NaCl, the k cat/K m value of XynA exhibited a 3.41-fold increase for beechwood
      xylan compared to no added NaCl, and the residual activity of XynA increased from
      23% (no added NaCl) to 58% after 1 h incubation at 45  degrees C. This may be the
      first report concerning a cold-adapted xylanase from a non-halophilic species
      that displays the highest activity at a NaCl concentration range from 3 to 5 M.
      The features of cold activity and salt tolerance suggest the potential
      application of XynA in the food industry and bioethanol production from marine
      seaweeds.

PMID- 24464290
TI  - Diffusion-weighted imaging as an aid in the diagnosis of the etiology of medial
      longitudinal fasciculus syndrome.
AB  - PURPOSE: Internuclear ophthalmoplegia is caused by a lesion; stroke, multiple
      sclerosis, brain metastases, or trauma may produce lesions of the medial
      longitudinal fasciculus (MLF). Imaging techniques, such as DWI, can help identify
      the site of the lesion in order to speed diagnosis and lead to appropriate
      treatment. METHODS: Over an 8-month period, eight consecutive patients with
      suspected MLF syndrome (most secondary to ischemic stroke) underwent MRI
      examinations, including DWI sequencing, at an academic center in Taiwan. RESULTS:
      In all eight patients, abnormal high-signal lesions were found close to the floor
      of the fourth ventricle on the dorsal side of the pons. A neuroanatomical
      comparison showed that the location of the lesions was identical to the
      anatomical position of the MLF. CONCLUSION: Using DWI, good clinico-radiological
      correlation was found in all eight ischemic stroke patients diagnosed with MLF
      syndrome. DWI may broaden the application of MRI in the diagnosis of MLF
      syndrome.

PMID- 24464291
TI  - The histone deacetylase inhibitor trichostatin a promotes totipotency in the male
      gametophyte.
AB  - The haploid male gametophyte, the pollen grain, is a terminally differentiated
      structure whose function ends at fertilization. Plant breeding and propagation
      widely use haploid embryo production from in vitro-cultured male gametophytes,
      but this technique remains poorly understood at the mechanistic level. Here, we
      show that histone deacetylases (HDACs) regulate the switch to haploid
      embryogenesis. Blocking HDAC activity with trichostatin A (TSA) in cultured male
      gametophytes of Brassica napus leads to a large increase in the proportion of
      cells that switch from pollen to embryogenic growth. Embryogenic growth is
      enhanced by, but not dependent on, the high-temperature stress that is normally
      used to induce haploid embryogenesis in B. napus. The male gametophyte of
      Arabidopsis thaliana, which is recalcitrant to haploid embryo development in
      culture, also forms embryogenic cell clusters after TSA treatment. Genetic
      analysis suggests that the HDAC protein HDA17 plays a role in this process. TSA
      treatment of male gametophytes is associated with the hyperacetylation of
      histones H3 and H4. We propose that the totipotency of the male gametophyte is
      kept in check by an HDAC-dependent mechanism and that the stress treatments used
      to induce haploid embryo development in culture impinge on this HDAC-dependent
      pathway. 

PMID- 24464293
TI  - Getting in Shape? Leaves work it out with KANADI1.

PMID- 24464292
TI  - ACTIN DEPOLYMERIZING FACTOR4 regulates actin dynamics during innate immune
      signaling in Arabidopsis.
AB  - Conserved microbe-associated molecular patterns (MAMPs) are sensed by pattern
      recognition receptors (PRRs) on cells of plants and animals. MAMP perception
      typically triggers rearrangements to actin cytoskeletal arrays during innate
      immune signaling. However, the signaling cascades linking PRR activation by MAMPs
      to cytoskeleton remodeling are not well characterized. Here, we developed a
      system to dissect, at high spatial and temporal resolution, the regulation of
      actin dynamics during innate immune signaling in plant cells. Within minutes of
      MAMP perception, we detected changes to single actin filament turnover in
      epidermal cells treated with bacterial and fungal MAMPs. These MAMP-induced
      alterations phenocopied an ACTIN DEPOLYMERIZING FACTOR4 (ADF4) knockout mutant.
      Moreover, actin arrays in the adf4 mutant were unresponsive to a bacterial MAMP,
      elf26, but responded normally to the fungal MAMP, chitin. Together, our data
      provide strong genetic and cytological evidence for the inhibition of ADF
      activity regulating actin remodeling during innate immune signaling. This work is
      the first to directly link an ADF/cofilin to the cytoskeletal rearrangements
      elicited directly after pathogen perception in plant or mammalian cells. 

PMID- 24464294
TI  - En Garde! Inhibition of an actin depolymerizing factor activates immune responses
      during plant-microbe interactions.

PMID- 24464295
TI  - Arabidopsis KANADI1 acts as a transcriptional repressor by interacting with a
      specific cis-element and regulates auxin biosynthesis, transport, and signaling
      in opposition to HD-ZIPIII factors.
AB  - The formation of leaves and other lateral organs in plants depends on the proper
      specification of adaxial-abaxial (upper-lower) polarity. KANADI1 (KAN1), a member
      of the GARP family of transcription factors, is a key regulator of abaxial
      identity, leaf growth, and meristem formation in Arabidopsis thaliana. Here, we
      demonstrate that the Myb-like domain in KAN1 binds the 6-bp motif GNATA(A/T) and
      that this motif alone is sufficient to squelch transcription of a linked reporter
      in vivo. In addition, we report that KAN1 acts as a transcriptional repressor.
      Among its targets are genes involved in auxin biosynthesis, auxin transport, and
      auxin response. Furthermore, we find that the adaxializing HD-ZIPIII
      transcription factor REVOLUTA has opposing effects on multiple components of the
      auxin pathway. We hypothesize that HD-ZIPIII and KANADI transcription factors
      pattern auxin accumulation and responsiveness in the embryo. Specifically, we
      propose the opposing actions of KANADI and HD-ZIPIII factors on cotyledon
      formation (KANADI represses and HD-ZIPIII promotes cotyledon formation) occur
      through their opposing actions on genes acting at multiple steps in the auxin
      pathway. 

PMID- 24464296
TI  - The BOY NAMED SUE quantitative trait locus confers increased meiotic stability to
      an adapted natural allopolyploid of Arabidopsis.
AB  - Whole-genome duplication resulting from polyploidy is ubiquitous in the
      evolutionary history of plant species. Yet, polyploids must overcome the meiotic
      challenge of pairing, recombining, and segregating more than two sets of
      chromosomes. Using genomic sequencing of synthetic and natural allopolyploids of
      Arabidopsis thaliana and Arabidopsis arenosa, we determined that dosage variation
      and chromosomal translocations consistent with homoeologous pairing were more
      frequent in the synthetic allopolyploids. To test the role of structural
      chromosomal differentiation versus genetic regulation of meiotic pairing, we
      performed sequenced-based, high-density genetic mapping in F2 hybrids between
      synthetic and natural lines. This F2 population displayed frequent dosage
      variation and deleterious homoeologous recombination. The genetic map derived
      from this population provided no indication of structural evolution of the genome
      of the natural allopolyploid Arabidopsis suecica, compared with its predicted
      parents. The F2 population displayed variation in meiotic regularity and pollen
      viability that correlated with a single quantitative trait locus, which we named
      BOY NAMED SUE, and whose beneficial allele was contributed by A. suecica. This
      demonstrates that an additive, gain-of-function allele contributes to meiotic
      stability and fertility in a recently established allopolyploid and provides an
      Arabidopsis system to decipher evolutionary and molecular mechanisms of meiotic
      regularity in polyploids. 

PMID- 24464297
TI  - Characteristics of adsorption interactions of cadmium(II) onto humin from peat
      soil in freshwater and seawater media.
AB  - The present study examined Cd solubility in pH 2-12 fresh and seawater media with
      and without humin to determine Cd species composition. The study, based on the
      Langmuir-Hinshelwood kinetics model, was conducted to determine the kinetic
      parameters of Cd(II) adsorption onto humin. We employed the Langmuir and
      Freundlich models to derive thermodynamic parameters. Aquo (Cd(H2O) 6 (2+) ) and
      chloro- (CdCl(+) and CdCl2) complexes were responsible for Cd(II) adsorption onto
      humin. Results showed Cd as Cd(II) and Cd(H2O) 6 (+2) was water soluble at 2 < pH
      < 7; with a portion of the soluble Cd precipitating as Cd(OH)2. The Cd(II) rate
      constant (k) in freshwater was 0.5 * 10(-3) (min(-1)), occurring in a single
      phase, while in seawater fast and slow phase values for k were 31.88 * 10(-3) and
      6.2 * 10(-3) (min(-1)), respectively. The adsorption curves showed a better fit
      with the Langmuir than the Freundlich model.

PMID- 24464298
TI  - Metal distribution in the tissues of two benthic fish from paddy fields in the
      middle reach of the Yangtze River.
AB  - Metal content was determined in two fish species (Misgurnus anguillicaudatus and
      Monopterus albus) inhabiting rice paddies along the Middle Reach of the Yangtze
      River. Both are species important food fish in East Asia. The levels of eight
      metals (Fe, Mn, Zn, Cu, Cr, As, Cd, Pb) in skin, muscle and intestinal tissues
      were measured and correlated with fish size. Metal distribution among the tissues
      was examined and the potential risk of fish consumption was evaluated.
      Correlations between metal concentration and fish size were not significant.
      Concentrations of essential metals varied significantly among tissues, but the
      differences were not significant for non-essential metals. Correlations among
      metals in skin tissue were stronger than in intestinal and muscle tissues. Metal
      concentrations in the edible tissues of both fish met permissible levels for
      consumption, except Pb in loach skin and Cr loach in muscle. The potential risk
      caused by Pb from skin and Cr from muscle of loach consumption should be
      considered in future risk assessmeents. 

PMID- 24464299
TI  - Effect of NIPRISAN(r) on CYP3A4 activity in vitro.
AB  - NIPRISAN((r)) is a phytomedicine developed from herbal products used in folkloric
      practice for the management of sickle cell disease (SCD). The effect of
      NIPRISAN((r)) was tested on human cytochrome P4503A4 drug metabolising enzyme to
      generate clinically significant data for its safe and efficacious use. Inhibitory
      activity on CYP3A4 was measured with and without the addition of NIPRISAN((r)),
      by testing different concentrations of the product at 37  degrees C in reactive
      mixtures with ketoconazole (2.5 MUM) as the positive control. Results showed a
      low IC(50) value of 0.06 mg/ml, indicating that metabolic processes of
      NIPRISAN((r)) are likely to inhibit CYP3A4. The result suggests possible herb
      drug interaction may occur, with potential implication on common medications that
      are CYP3A4 substrates. It is, therefore, advocated that concomitant
      administration of NIPRISAN((r)) along with medications that are CYP3A4 substrates
      should be done with caution so as not to compromise NIPRISAN((r)')s established
      beneficial effect in the management of SCD.

PMID- 24464300
TI  - Connective tissue growth factor (CCN2) and microRNA-21 are components of a
      positive feedback loop in pancreatic stellate cells (PSC) during chronic
      pancreatitis and are exported in PSC-derived exosomes.
AB  - Pancreatitis is an inflammatory condition of the pancreas which, in its chronic
      form, involves tissue destruction, exocrine and endocrine insufficiency,
      increased risk of pancreatic cancer, and an extensive fibrotic pathology which is
      due to unrelenting collagen deposition by pancreatic stellate cells (PSC). In
      response to noxious agents such as alcohol-excessive consumption of which is a
      major cause of pancreatitis in the West-normally quiescent PSC undergo a
      phenotypic and functional transition to activated myofibroblasts which produce
      and deposit collagen at high levels. This process is regulated by connective
      tissue growth factor (CCN2), expression of which is highly up-regulated in
      activated PSC. We show that CCN2 production by activated PSC is associated with
      enhanced expression of microRNA-21 (miR-21) which was detected at high levels in
      activated PSC in a murine model of alcoholic chronic pancreatitis. A positive
      feedback loop between CCN2 and miR-21 was identified that resulted in enhancement
      of their respective expression as well as that of collagen alpha1(I). Both miR-21
      and CCN2 mRNA were present in PSC-derived exosomes, which were characterized as
      50-150 nm CD9-positive nano-vesicles. Exosomes from CCN2-GFP- or miR-21-GFP
      transfected PSC were taken up by other PSC cultures, as shown by direct
      fluorescence or qRT-PCR for GFP. Collectively these studies establish miR-21 and
      CCN2 as participants in a positive feedback loop during PSC activation and as
      components of the molecular payload in PSC-derived exosomes that can be delivered
      to other PSC. Thus interactions between cellular or exosomal miR-21 and CCN2
      represent novel aspects of fibrogenic regulation in PSC. Summary Chronic injury
      in the pancreas is associated with fibrotic pathology which is driven in large
      part by CCN2-dependent collagen production in pancreatic stellate cells. This
      study shows that CCN2 up-regulation in PSC is associated with increased
      expression of miR-21 which, in turn, is able to stimulate CCN2 expression further
      via a positive feedback loop. Additionally miR-21 and CCN2 were identified in PSC
      derived exosomes which effected their delivery to other PSC. The cellular and
      exosomal miR-21-CCN2 axis is a novel component in PSC fibrogenic signaling. 

PMID- 24464301
TI  - Functional improvement of self-care in the elderly after hip fracture: is age a
      factor?
AB  - INTRODUCTION: The aging population is growing rapidly in Asia resulting in an
      increased number of hip fractures being managed surgically. Though there is
      evidence of improved quality of patient care and outcomes with well-established
      models of care, we do not know if the functional recovery in activities of daily
      living among this group of patients is also dependant on age. We hypothesize that
      there will be a difference in Modified Barthel Index (MBI) scores between the
      'older old' (>85 years) and the 'younger old' (<85 years). PATIENT AND METHODS:
      Hip fracture patients (>60 years) treated surgically were divided into Group A
      (below 85 years) and Group B (above 85 years). Demographic data, Charlson's
      Comorbidity Index (CCI) score, time to surgery and length of stay (LOS) were
      recorded. To assess the recovery in activities of daily living, the MBI scores
      were measured for the following intervals; pre-fall, at discharge, at 6-month and
      at 1-year follow-up. RESULTS: The mean age for Group A (n = 120) was 77 years (60
      85) and the mean age for Group B (n = 59) was 91.8 years (86-108). There was no
      significant difference in the mean CCI (A: 1.14, B: 1.24), mean time to surgery
      (A: 72.3 h, B: 79.9 h) and mean LOS (A: 10.8 days, B: 10.3 days). The MBI scores
      were significantly different (P < 0.05) for the pre-injury scores (A = 91.5, B =
      84.4); however, there was no significant difference for scores measured at
      discharge (A = 57.5, B = 52.7), at 6 months (A = 74.6, B = 69.3) and at 1 year (A
      = 82.2, B = 73.2). Though there was a significant improvement, the scores at 1
      year were significantly lower than the pre-injury score for both groups.
      CONCLUSION: We conclude that age is not a factor in determining functional
      recovery with regard to activities of daily living in an integrated model of care
      for geriatric hip fracture patients.

PMID- 24464302
TI  - Ferromagnetic CaRuO3.
AB  - The non-magnetic and non-Fermi-liquid CaRuO3 is the iso-structural analog of the
      ferromagnetic (FM) and Fermi-liquid SrRuO3. We show that an FM order in the
      orthorhombic CaRuO3 can be established by the means of tensile epitaxial strain.
      The structural and magnetic property correlations in the CaRuO3 films formed on
      SrTiO3 (100) substrate establish a scaling relation between the FM moment and the
      tensile strain. The strain dependent crossover from non-magnetic to FM CaRuO3 was
      observed to be associated with switching of non-Fermi liquid to Fermi-liquid
      behavior. The intrinsic nature of this strain-induced FM order manifests in the
      Hall resistivity too; the anomalous Hall component realizes in FM tensile
      strained CaRuO3 films on SrTiO3 (100) whereas the non-magnetic compressive
      strained films on LaAlO3 (100) exhibit only the ordinary Hall effect. These
      observations of an elusive FM order are consistent with the theoretical
      predictions of scaling of the tensile epitaxial strain and the magnetic order in
      tensile CaRuO3. We further establish that the tensile strain is more efficient
      than the chemical route to induce FM order in CaRuO3. 

PMID- 24464303
TI  - Using risk prediction tools in survivors of in-hospital cardiac arrest.
AB  - In-hospital cardiac arrests are common and associated with poor outcomes.
      Predicting the likelihood of favorable neurological survival following
      resuscitation from an in-hospital cardiac arrest could provide important
      information for physicians and families. In this article, we review the
      literature regarding predictors of survival following in-hospital cardiac arrest.
      Specifically, we describe the Cardiac Arrest Survival Postresuscitation In
      hospital (CASPRI) score that was recently developed and validated using data from
      the Get With the Guidelines-Resuscitation registry. The CASPRI score includes 11
      predictor variables: age, initial cardiac arrest rhythm, defibrillation time,
      baseline neurological status, duration of resuscitation, mechanical ventilation,
      renal insufficiency, hepatic insufficiency, sepsis, malignancy, and hypotension.
      The score is simple to use at the bedside, has excellent discrimination and
      calibration, and provides robust estimates of the probability of favorable
      neurological survival after an in-hospital cardiac arrest. Thus, CASPRI may be
      valuable in establishing expectations by physicians and families in the critical
      period after these high-risk events.

PMID- 24464304
TI  - Medication adherence and heart failure.
AB  - Heart failure remains among the most prevalent and burdensome medical conditions
      in the United States. With increasing awareness regarding resource use and costs
      of care, there has been significant interest in the identification of factors
      that influence rates of hospitalization and readmission in individuals with heart
      failure. Medication adherence has been identified as one such modifiable factor.
      Many barriers to medication adherence have been identified and include factors
      related to the patient, those related to their medical condition, their medical
      regimen, the healthcare system and others that are social and socioeconomic in
      nature. Identification of these barriers has led to novel interventions for
      improving medication adherence with the goal of improving the care of individuals
      with heart failure.

PMID- 24464305
TI  - Cardiac PET-CT for monitoring medical and interventional therapy in patients with
      CAD: PET alone versus hybrid PET-CT?
AB  - This review focuses on optimal use of PET and PET-CT in monitoring medical and
      interventional therapy in patients with CAD. PET provides quantitative
      measurement of absolute myocardial blood flow and thus permits comprehensive
      physiological assessment of the coronary circulation. Hybrid PET-CT, in
      particular CCTA, adds anatomical information to maximal MBF measurement and so
      facilitates distinction of triple vessel focal epicardial disease from coronary
      microvascular disease or diffuse coronary atherosclerosis without focal stenoses.
      Hybrid PET-CT also may be of value in determining appropriateness and feasibility
      of percutaneous interventional therapy for chronic total coronary occlusion. PET
      alone, however, is the preferred modality to address functional status of the
      coronary circulation and response over time, if required, to medical or
      interventional therapy. CT at a minimum provides attenuation correction. More
      detailed CCTA should be added only when a well-defined need for anatomical
      information is required to answer the clinical question posed.

PMID- 24464306
TI  - Statin treatment, new-onset diabetes, and other adverse effects: a systematic
      review.
AB  - Statin treatment prevents cardiovascular diseases probably beyond their lipid
      lowering effect. Increasing evidence suggests that statins might increase the
      risk of new-onset diabetes; however, diabetes is known to increase the risk of
      cardiovascular diseases. The majority of the literature suggests an increased
      risk of new-onset diabetes in patients treated with statins in a number of
      different settings and that the risk appears greatest among the more potent
      statins. Furthermore, a dose-response curve has been shown between statin
      treatment and the development of diabetes. Possible mechanisms include muscle
      insulin resistance, lower expression of GLUT-4 in adipocytes impairing glucose
      tolerance and suppression of glucose-induced elevation of intracellular Ca(2+)
      level. However, other side effects have been reported such as increased risk of
      myotoxicity, increased liver enzymes, cataracts, mood disorders, dementias,
      hemorrhagic stroke and peripheral neuropathy, which should maybe be added to the
      increased risk of new-onset diabetes, when considering the risk- benefit ratio of
      statin treatment.

PMID- 24464307
TI  - Management of symptomatic carotid disease in 2014.
AB  - Extracranial carotid artery stenosis accounts for up to 12 % of stroke, the third
      leading cause of death in industrialized nations. Carotid stenoses leading to
      transient or permanent neurologic or retinal symptoms within the preceding 6
      months are deemed symptomatic and require prompt noninvasive evaluation and
      treatment. Preventive medical therapy is standard for symptomatic carotid
      stenosis and continues to evolve. Landmark trials have proven carotid
      endarterectomy (CEA) superior to medical therapy for stroke prevention in
      symptomatic lesions. Modern investigations have proven carotid artery stenting
      (CAS) non-inferior to CEA, and the strength of the combined data has led to a
      class I recommendation for CEA or CAS in patients with high grade symptomatic
      carotid stenosis, provided the risk of perioperative events is acceptable.
      Evidence-based modern management of symptomatic carotid stenosis is reviewed
      here.

PMID- 24464308
TI  - Current state of anticoagulants to treat deep venous thrombosis.
AB  - Anticoagulation remains the cornerstone of treatment in patients with deep vein
      thrombosis (DVT). While parenteral anticoagulants and oral vitamin K antagonists
      (e.g., warfarin) have been used for many decades, the recent development of novel
      oral anticoagulants have provided clinicians with an expanding set of therapeutic
      options for DVT. This review summarizes the pharmacology and clinical trial
      results of these new oral anticoagulants. Several practical considerations to the
      use of these oral anticoagulants including issues related to adherence,
      monitoring, and reversal are also discussed.

PMID- 24464309
TI  - Ibrutinib: first global approval.
AB  - Ibrutinib (ImbruvicaTM) is a small molecule, first-in-class, once-daily, orally
      available, Bruton's tyrosine kinase inhibitor that is under development for the
      treatment of B cell malignancies, including chronic lymphocytic leukaemia (CLL),
      mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL), as well as
      multiple myeloma (MM), follicular lymphoma (FL) and Waldenstrom's
      macroglobulinemia (WM). It has been developed by Pharmacyclics, Inc. and Janssen
      Biotech, Inc. Ibrutinib acts by blocking B-cell antigen receptor signalling,
      thereby reducing malignant proliferation of B cells and inducing cell death.
      Based chiefly on findings from a phase Ib/II study, ibrutinib has been approved
      in the USA for the treatment of MCL in previously treated patients and is one of
      the first approvals through the US FDA's Breakthrough Therapy Designation
      Pathway. An application has been filed in the EU seeking regulatory approval in
      this indication. In both the USA and EU, further applications have been filed
      with regulatory bodies seeking approval for the use of ibrutinib in patients with
      previously treated CLL/small lymphocytic lymphoma (SLL). Phase III trials are
      underway worldwide to evaluate ibrutinib in the treatment of patients with
      CLL/SLL, DLBCL and MCL, and the agent is in phase II development for use in WM,
      FL and MM. This article summarizes the milestones in the development of ibrutinib
      leading to its first approval in MCL. 

PMID- 24464310
TI  - ZnO nanorods/ZnS.(1,6-hexanediamine)(0.5) hybrid nanoplates hierarchical
      heteroarchitecture with improved electrochemical catalytic properties for
      hydrazine.
AB  - Novel hierarchical heteronanostructures of ZnO nanorods/ZnS.(HDA)0.5 (HDA = 1,6
      hexanediamine) hybrid nanoplates on a zinc substrate are successfully synthesized
      on a large scale by combining hydrothermal growth (for ZnO nanorods) and liquid
      chemical conversion (for ZnS.(HDA)0.5 nanoplates) techniques. The formation of
      ZnS.(HDA)0.5 hybrid nanoplates branches takes advantage of the preferential
      binding of 1,6-hexanediamine on specific facets of ZnS, which makes the
      thickening rate much lower than the lateral growth rate. The ZnS.(HDA)0.5 hybrid
      nanoplates have a layered structure with 1,6-hexanediamine inserted into
      interlayers of wurtzite ZnS through the bonding of nitrogen. The number density
      and thickness of the secondary ZnS.(HDA)0.5 nanoplates can be conveniently
      engineered by variation of the sulfur source and straightforward adjustment of
      reactant concentrations such as 1,6-hexanediamine and the sulfur source. The
      fabricated ZnO/ZnS.(HDA)0.5 heteronanostructures show improved electrochemical
      catalytic properties for hydrazine compared with the primary ZnO nanorods. Due to
      its simplicity and efficiency, this approach could be similarly used to fabricate
      varieties of hybrid heterostructures made of materials with an intrinsic large
      lattice mismatch. 

PMID- 24464311
TI  - QTL mapping and development of candidate gene-derived DNA markers associated with
      seedling cold tolerance in rice (Oryza sativa L.).
AB  - Cold stress at the seedling stage is a major threat to rice production. Cold
      tolerance is controlled by complex genetic factors. We used an F7 recombinant
      inbred line (RIL) population of 123 individuals derived from a cross of the cold
      tolerant japonica cultivar Jinbu and the cold-susceptible indica cultivar BR29
      for QTL mapping. Phenotypic evaluation of the parents and RILs in an 18/8 
      degrees C (day/night) cold stress regime revealed continuous variation for cold
      tolerance. Six QTLs including two on chromosome 1 and one each on chromosomes 2,
      4, 10, and 11 for seedling cold tolerance were identified with phenotypic
      variation (R(2)) ranging from 6.1 to 16.5 %. The QTL combinations (qSCT1 and
      qSCT11) were detected in all stable cold-tolerant RIL groups, which explained the
      critical threshold of 27.1 % for the R(2) value determining cold tolerance at the
      seedling stage. Two QTLs (qSCT1 and qSCT11) on chromosomes 1 and 11,
      respectively, were fine mapped. The markers In1-c3, derived from the open reading
      frame (ORF) LOC_Os01g69910 encoding calmodulin-binding transcription activator
      (CAMTA), and In11-d1, derived from ORF LOC_Os11g37720 (Duf6 gene), co-segregated
      with seedling cold tolerance. The result may provide useful information on
      seedling cold tolerance mechanism and provide DNA markers for a marker-assisted
      breeding program to improve seedling cold tolerance in indica rice varieties.

PMID- 24464313
TI  - Maternal body composition and birth weight.

PMID- 24464312
TI  - Differences between amyloid-beta aggregation in solution and on the membrane:
      insights into elucidation of the mechanistic details of Alzheimer's disease.
AB  - The association of the amyloid-beta (Abeta) peptide with cellular membranes is
      hypothesized to be the underlying phenomenon of neurotoxicity in Alzheimer's
      disease. Misfolding of proteins and peptides, as is the case with Abeta, follows
      a progression from a monomeric state, through intermediates, ending at long,
      unbranched amyloid fibers. This tutorial review offers a perspective on the
      association of toxic Abeta structures with membranes as well as details of
      membrane-associated mechanisms of toxicity. 

PMID- 24464314
TI  - Density functional investigations on 2-naphthalenecarbonitrile dimerization
      within cucurbit[8]uril cavitand.
AB  - Dimerization of 2-naphthalenecarbonitrile (2-NpCN) mediated by cucurbit[8]uril
      (CB[8]) has been investigated employing the density functional theory. Different
      structures of 2-NpCN dimers were generated by combining monomers in anti-head-to
      head (A), anti-head-to-tail (B) and syn-head-to-tail (C) fashion. All these
      dimeric structures possess rigid cube-like architecture. On confinement within
      the CB[8] dimer A turns out to be the lowest energy structure. Calculated (1)H
      NMR spectra revealed that the 2-NpCN dimer exhibits large shielding for aromatic
      protons consistent with the experiment. The protons attached to cubane moiety on
      the other hand, led to down-field signals. Dimerization mediated with CB[8]
      cavitand is further accompanied by the frequency up-shift (blue shift) of
      methylene stretching vibration in its infrared spectra.

PMID- 24464315
TI  - Theoretical study of X- . 1 . YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br,
      I, PH2 and AsH2): noncovalently electron-withdrawing effects on anion-arene
      interactions.
AB  - The ternary complexes X(-) . 1 . YF (1 = triazine, X = Cl, Br and I, Y = H, Cl,
      Br, I, PH2 and AsH2) have been investigated by MP2 calculations to understand the
      noncovalently electron-withdrawing effects on anion-arene interactions. The
      results indicate that in binary complexes (1 . X(-)), both weak sigma-type and
      anion-pi complexes can be formed for Cl(-) and Br(-), but only anion-pi complex
      can be formed for I(-). Moreover, the hydrogen-bonding complex is the global
      minimum for all three halides in binary complexes. However, in ternary complexes,
      anion-pi complex become unstable and only sigma complex can retain in many cases
      for Cl(-) and Br(-). Anion-pi complex keeps stable only when YF = HF. In contrast
      with binary complexes, sigma complex become the global minimum for Cl(-) and Br(
      ) in ternary complexes. These changes in binding mode and strength are consistent
      with the results of covalently electron-withdrawing effects. However, in contrast
      with the covalently electron-withdrawing substituents, Cl(-) and Br(-) can attack
      the aromatic carbon atom to form a strong sigma complex when the noncovalently
      electron-withdrawing effect is induced by halogen bonding. The binding behavior
      for I(-) is different from that for Cl(-) and Br(-) in two aspects. First, the
      anion-pi complex for I(-) can also keep stable when the noncovalent interaction
      is halogen bonding. Second, the anion-pi complex for I(-) is the global minimum
      when it can retain as a stable structure. 

PMID- 24464316
TI  - Quantitative characterization of protein tertiary motifs.
AB  - A quantitative feature-vector representation/model of tertiary structural motifs
      of proteins is presented. Multiclass logistic regression and a probabilistic
      neural network were employed to apply this representation to large data sets in
      order to classify them into major families of distinct motif types (including
      those of functional importance) with high statistical confidence. Scatter plots
      of random samples of these motifs were obtained through two-dimensional
      transformation of the feature vector by metric MDS (multidimensional scaling).
      The plots showed distinct clusters and shapes for different families and
      demonstrated the relevance and importance of the proposed quantitative feature
      vector representation for characterizing protein tertiary structural motifs. The
      relative importance of the features was analyzed. The scope of the present work
      to investigate Nature's prioritization and optimization of functional motif
      structures is highlighted. 

PMID- 24464317
TI  - Density functional studies of the stepwise substitution of pyridine, pyridazine,
      pyrimidine, pyrazine, and 1,3,5-triazine with BCO.
AB  - The structures, stabilities, and aromaticities of a series of (BCO) n (CH)5-n N
      (n = 0-5), (BCO) n (CH)4-n N2 (n = 0-4), and 1,3,5-(BCO) n (CH)3-n N3 (n = 0-3)
      clusters were investigated at the B3LYP density functional level of theory. The
      most stable positional isomers of individual clusters were obtained. All of the
      calculated CO binding energies were positive, suggesting that the BCO-substituted
      species are stable. It was found that the BCO-substituted structures are much
      less strained than their carbocation counterparts. The negative nucleus
      independent chemical shifts (NICSs) obtained show that all of the BCO-substituted
      species possess three-dimensional aromaticity, in good accord with the
      aromaticities of the corresponding hydrocarbon species.

PMID- 24464318
TI  - A 30-year epidemiologic survey (1974-2003) of haematological malignancies on the
      island of Sardinia: temporal changes in incidence and a geographic comparison of
      incidence rates.
AB  - In a previous survey of newly diagnosed haematological malignancies (HMs) in
      Sardinia from 1974 to 1993, we observed a marked increase in the incidence of
      many HMs that we chiefly attributed to improvements in case ascertainment. To
      better define the nature of this increase, we extended the survey by an
      additional decade (1994-2003), applying the same previously used methods. The
      incidence of HMs further increased from 1994 to 2003. The incidence rate of total
      HMs (THMs), standardised to the world population, was 30.15 * 10(5) person-years
      vs. 21.58 from 1984 to 1993 and 15.26 from 1974 to 1983. The temporal variations
      in the incidence differed in different HMs and were correlated with the diseases
      clinical characteristics and the increased availability of diagnostic tools and
      skills in Sardinia. These observations support the hypothesis that the temporal
      differences in the incidence rates observed for many HMs in Sardinia over the 30
      year survey period were caused by temporal differences in diagnostic efficiency
      rather than by disease occurrence. An important exception was the increase in non
      Hodgkin's lymphoma, which represents a true increase in occurrence, similarly to
      most Western countries. The incidence rates of HMs already having or reaching
      stable values in the decade 1994-2003 were similar to those of most Western
      countries. No significant evidence emerged to suggest that Sardinian
      particularities influenced the occurrence of HMs. This study demonstrates the
      extent to which diagnostic efficiency can influence incidence evaluations and
      emphasises the importance of prolonged observation to determine the validity of
      incidence rates for both temporal and geographic comparisons. 

PMID- 24464319
TI  - Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia
      using filter paper cards.
AB  - The lack of molecular diagnosis in the field of cancer in Iraq has motivated us
      to perform a genetic analysis of pediatric acute myelogenous leukemia (AML),
      including class I and II aberrations. Peripheral blood or bone marrow cells were
      collected from 134 AML children aged <=15 years. Flinders Technology Associates
      (FTA) filter paper cards were used to transfer dried blood samples from five
      Iraqi hospitals to Japan. DNA sequencing was performed to identify class I
      mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL
      rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS
      like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were
      analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples,
      the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I
      mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD,
      and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %),
      and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts,
      respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1
      mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of
      AML children were proved to carry favorable prognostic genetic abnormalities,
      whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special
      treatment plan including allogeneic hematopoietic stem cell transplantation.
      Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is
      likely that molecular diagnosis using FTA cards in underdeveloped countries could
      guide doctors towards an appropriate treatment strategy. 

PMID- 24464320
TI  - In memoriam Professor Helmut Loffler.

PMID- 24464321
TI  - Does early intervention prevent health-risking sexual behaviors related to
      HIV/AIDS?

PMID- 24464322
TI  - Sex on the beach: the influence of social norms and trip companion on spring
      break sexual behavior.
AB  - Spring Break trips are associated with heavy drinking and with risky sexual
      behavior (e.g., unprotected sex, multiple partners, unwanted sexual contact),
      especially for those students who go on trips with friends. The present study
      adds to this growing event-specific risk literature by examining Spring Break
      specific normative perceptions of sexual risk behavior and the role that these
      perceptions and taking a trip with a friend or with a romantic partner have on
      Spring Break sexual behavior. College students (N = 1,540; 53.9 % female) were
      asked to report descriptive normative perceptions of sex with casual partners,
      drinking prior to sex, number of drinks prior to sex, and condom use as well as
      their own Spring Break drinking and sexual behaviors. Students perceived the
      typical same-sex student to have engaged in more frequent sexual behavior for all
      outcomes than students' own self-reported sexual behavior. Furthermore, results
      revealed that these perceptions were positively associated with behavior. The
      choice of travel companion (friend(s) versus romantic partner) also
      differentially predicted sexual behaviors. Results suggested that intervention
      efforts aimed at reducing risks for Spring Break trip-takers may be strongest
      when they incorporate corrective normative information and target those traveling
      with friends. 

PMID- 24464323
TI  - Toward the development of preventive interventions to reduce HRSB, HIV/AIDS, and
      multiple problem behaviors.

PMID- 24464324
TI  - Venue-based network analysis to inform HIV prevention efforts among young gay,
      bisexual, and other men who have sex with men.
AB  - In the USA, human immunodeficiency virus (HIV) incidence rates continue to
      increase among young gay, bisexual, and other men have sexual intercourse with
      men. Young men who have sex with men (YMSM) indicate interest in HIV prevention
      programming that is implemented in the social venues that they frequent when they
      want to socialize with other men. We sought to understand YMSM venues as a
      networked space to provide insights into venue-based HIV prevention intervention
      delivery. The present study used survey data reported by 526 YMSM (ages 18-24) in
      2005 to conduct a venue-based social network analysis. The latter sought to
      determine if the structure and composition of the networks in Los Angeles could
      be used to facilitate the delivery of HIV prevention messages to YMSM. Degree of
      person sharing between venues was used to demonstrate interconnectivity between
      venues classified as low risk (e.g., coffee shops) and high risk (e.g., bars and
      clubs) by a Community Advisory Board. Sixty-five percent of the 110 venues
      nominated were bars and clubs. Nearly all YMSM were connected by a single venue
      and over 87 % were connected by the six most central venues. A handful of highly
      connected low-risk venues was central to the venue network and connected to
      popular high-risk venues. Venue-based network analysis can inform tailored HIV
      prevention messaging for YMSM. Targeted delivery of prevention messaging at low
      risk centralized venues may lead to widespread diffusion among venue-attending
      YMSM. 

PMID- 24464325
TI  - Endorsement of compulsory HIV vaccination policy among populations at high risk
      of HIV exposure (LA VOICES).
AB  - Compulsory vaccination is a frequently implemented policy option for ensuring
      comprehensive vaccine coverage. Ongoing controversies around human papillomavirus
      vaccine dissemination, and suboptimal coverage, suggest the value of assessing
      acceptability of compulsory vaccinations-particularly among likely target
      populations-in advance of their public availability to support evidence-informed
      interventions. With the first HIV vaccine to demonstrate partial efficacy in a
      large-scale clinical trial, we examined individual characteristics and attitudes
      associated with support for compulsory HIV vaccination policy among a diverse,
      representative sample of adults attending probable HIV vaccine dissemination
      venues in a large urban county. Participants were recruited using three-stage
      probability sampling from likely venues for future HIV vaccine dissemination. We
      used Audio-CASI to administer a 60-min structured questionnaire. Items included
      endorsement of compulsory HIV vaccination policy, sociodemographic
      characteristics, injecting drug use, vaccine attitudes and perceived HIV risk.
      Among 1,225 participants (mean age = 36.8 years; 55.6 % males, 37.6 % non-English
      speaking Hispanic, 78.8 % heterosexual, 25.7 % injection drug users), almost half
      (48.2 %) endorsed a compulsory HIV vaccination policy. Non-English speaking
      Hispanics compared to whites, participants with less than high school education,
      higher positive vaccine attitude scores and higher perceived HIV risk were
      significantly more likely, and people who inject drugs significantly less likely
      to endorse compulsory HIV vaccination. Public health interventions to promote
      positive vaccine attitudes and accurate perceptions of HIV risk among vulnerable
      populations, and strategies tailored for people who inject drugs, may build
      support for compulsory HIV vaccination policy and promote broad HIV vaccine
      coverage. 

PMID- 24464326
TI  - Psychiatric Comorbidity at the Time of Diagnosis in Adults With ADHD: The CAT
      Study.
AB  - OBJECTIVE: The CAT (Comorbilidad en Adultos con TDAH) study aimed to quantify and
      characterize the psychiatric comorbidity at the time of diagnosis of ADHD in
      adult outpatients. METHOD: Cross-sectional, multicenter, observational register
      of adults with ADHD diagnosed for the first time. RESULTS: In this large sample
      of adult ADHD (n = 367), psychiatric comorbidities were present in 66.2% of the
      sample, and were more prevalent in males and in the hyperactive-impulsive and
      combined subtypes. The most common comorbidities were substance use disorders
      (39.2%), anxiety disorders (23%), and mood disorders (18.1%). In all, 88.8%
      patients were prescribed pharmacological treatment for ADHD (in 93.4% of cases,
      modified release methylphenidate capsules 50:50). CONCLUSION: A high proportion
      of psychiatric comorbidity was observed when adult outpatients received a first
      time diagnosis of ADHD. The systematic registering of patients and comorbidities
      in clinical practice may help to better understand and manage the prognostic
      determinants in adult ADHD.

PMID- 24464327
TI  - Efficacy and Safety of Omega-3/6 Fatty Acids, Methylphenidate, and a Combined
      Treatment in Children With ADHD.
AB  - OBJECTIVE: To compare efficacy of Omega-3/6 fatty acids (Equazen eye qTM) with
      methylphenidate (MPH) and combined MPH + Omega-3/6 in children with ADHD. METHOD:
      Participants ( N = 90) were randomized to Omega-3/6, long-acting MPH, or
      combination for 12 months. ADHD symptoms were assessed using the ADHD Rating
      Scale and Clinical Global Impressions-Severity (CGI-S) scale. RESULTS: ADHD
      symptoms decreased in all treatment arms. Although significant differences
      favoring Omega + MPH over Omega-3/6 alone were found for ADHD Total and
      Hyperactivity-Impulsivity subscales, results on the Inattention subscale were
      similar. CGI-S scores decreased slowly and consistently with Omega-3/6, compared
      with a rapid decrease and subsequent slight increase in the MPH-containing arms.
      Adverse events were numerically less frequent with Omega-3/6 or MPH + Omega-3/6
      than MPH alone. CONCLUSION: The tested combination of Omega-3/6 fatty acids had
      similar effects to MPH, whereas the MPH + Omega combination appeared to have some
      tolerability benefits over MPH.

PMID- 24464328
TI  - Treatment With Lisdexamfetamine Dimesylate Improves Self- and Informant-Rated
      Executive Function Behaviors and Clinician- and Informant-Rated ADHD Symptoms in
      Adults: Data From a Randomized, Double-Blind, Placebo-Controlled Study.
AB  - OBJECTIVE: To examine the level of agreement between self- and observer-reported
      ratings of ADHD symptoms and executive function (EF) behaviors in adults with
      moderate to severe ADHD and EF deficits. METHOD: During a 10-week, randomized,
      double-blind, placebo-controlled study, the effect of lisdexamfetamine dimesylate
      (LDX) on EF was assessed by self-report and informant report (Behavior Rating
      Inventory of Executive Function-Adult Version), and ADHD symptoms were assessed
      by clinician- and informant-rated scales (ADHD Rating Scale IV with adult prompts
      and Conners' Adult ADHD Rating Scales-Observer Report: Short Version,
      respectively). Post hoc analysis used Pearson correlations to assess
      relationships between self- and informant-rated EF and clinician- and informant
      rated ADHD symptoms. RESULTS: Correlations between self-ratings versus informant
      ratings and clinician versus informant ratings were greater at Week 10/early
      termination (EF: placebo [0.5231-0.6085], LDX [0.3543-0.5167]; ADHD symptoms:
      placebo [0.4169], LDX [0.4004]) versus baseline (EF: placebo [0.3208-0.5023], LDX
      [0.2852-0.3439]; ADHD symptoms: placebo [0.1511], LDX [-0.0408]). CONCLUSION: LDX
      improved EF and ADHD symptoms, based on participant, informant, and clinician
      ratings. Increased rater agreement over time may reflect improved symptom
      awareness.

PMID- 24464329
TI  - Impacts of pesticides in a Central California estuary.
AB  - Recent and past studies have documented the prevalence of pyrethroid and
      organophosphate pesticides in urban and agricultural watersheds in California.
      While toxic concentrations of these pesticides have been found in freshwater
      systems, there has been little research into their impacts in marine receiving
      waters. Our study investigated pesticide impacts in the Santa Maria River
      estuary, which provides critical habitat to numerous aquatic, terrestrial, and
      avian species on the central California coast. Runoff from irrigated agriculture
      constitutes a significant portion of Santa Maria River flow during most of the
      year, and a number of studies have documented pesticide occurrence and biological
      impacts in this watershed. Our study extended into the Santa Maria watershed
      coastal zone and measured pesticide concentrations throughout the estuary,
      including the water column and sediments. Biological effects were measured at the
      organism and community levels. Results of this study suggest the Santa Maria
      River estuary is impacted by current-use pesticides. The majority of water
      samples were highly toxic to invertebrates (Ceriodaphnia dubia and Hyalella
      azteca), and chemistry evidence suggests toxicity was associated with the
      organophosphate pesticide chlorpyrifos, pyrethroid pesticides, or mixtures of
      both classes of pesticides. A high percentage of sediment samples were also toxic
      in this estuary, and sediment toxicity occurred when mixtures of chlorpyrifos and
      pyrethroid pesticides exceeded established toxicity thresholds. Based on a
      Relative Benthic Index, Santa Maria estuary stations where benthic
      macroinvertebrate communities were assessed were degraded. Impacts in the Santa
      Maria River estuary were likely due to the proximity of this system to Orcutt
      Creek, the tributary which accounts for most of the flow to the lower Santa Maria
      River. Water and sediment samples from Orcutt Creek were highly toxic to
      invertebrates due to mixtures of the same pesticides measured in the estuary.
      This study suggests that the same pyrethroid and organophosphate pesticides that
      have been shown to cause water and sediment toxicity in urban and agriculture
      water bodies throughout California, have the potential to affect estuarine
      habitats. The results establish baseline data in the Santa Maria River estuary to
      allow evaluation of ecosystem improvement as management initiatives to reduce
      pesticide runoff are implemented in this watershed. 

PMID- 24464330
TI  - Assessment of trace metals and porphyrins in excreta of Humboldt penguins
      (Spheniscus humboldti) in different locations of the northern coast of Chile.
AB  - To add data on trace metal contamination of Humboldt penguins in the South
      Pacific, levels of trace metals (As, Hg, Pb, Cu, Zn, and Cd) and porphyrins
      (copro-, uro-, and proto-) in excreta of Humboldt penguins that inhabit some
      important nesting sites on the northern coast of Chile were determined. Fresh
      excreta were collected on Pan de Azucar Island, Chanaral Island, and Cachagua
      Island, from December 2011 to January 2012. Concentration of metals was
      determined by flame atomic absorption spectrophotometry, whereas porphyrins
      levels were measured by fluorimetric analysis. Concentrations (dry weight) of Cu
      (199.67 MUg g(-1)), As (7.85 MUg g(-1)), and Pb (12.78 MUg g(-1)) were higher (p
      <= 0.05) in Cachagua Island. Colonies from Pan de Azucar Island showed the
      highest levels of Hg (0.76 MUg g(-1)), Cd (47.70 MUg g(-1)), and Zn (487.10 MUg
      g(-1)). Samples from Cachagua Island showed the highest (p <= 0.05) levels of
      copro- (2.16 nmol g(-1)), uro- (2.20 nmol g(-1)), and protoporphyrins (2.23 nmol
      g(-1)). There was a positive correlation between the metals As, Pb, and Cu with
      uro-, copro-, and protoporphyrins. The results indicated that penguin colonies
      from Cachagua Island are more exposed to metal contamination than penguin
      colonies from Pan de Azucar and Chanaral Islands, thus being more likely to
      develop certain diseases caused by contamination with metals. Considering
      biomagnification, the metals detected in the excreta of Humboldt penguins can be
      a source of contamination from marine environments to terrestrial ecosystems,
      which could also affect other living organisms. 

PMID- 24464331
TI  - [Incidence and duration of therapy of pathological hip findings in U2 and U3
      examinations (SNiP study)].
AB  - INTRODUCTION AND OBJECTIVES: Determination of the efficacy of an early ultrasound
      examination followed by immediate treatment of hip joint dysplasia as well as
      measuring the therapeutic success in a population-based cohort study of neonates.
      MATERIAL AND METHODS: The Survey of Neonates in Pomerania (SNiP) study included
      4,093 neonates which represents 95.1 % of the total neonatal population. Of these
      children 2,534 (61.9 %) underwent ultrasound examination of the hip joint during
      the U2 stage (3-10 days after birth). The mean gestational age was 38.9 weeks.
      The sonographic classification was performed according to Graf. RESULTS:
      Initially (U2 stage) 42 (1.66 %) children were reported to be in need of therapy
      (stage IIc or higher according to Graf). The analysis showed a significantly
      higher incidence in girls (32 girls vs. 10 boys, p < 0.023, chi(2) test) and in
      children who had a breech birth (116, 4.6 %). A genetic predisposition was
      ascertained in 180 (7.1 %) children. The children could be subdivided into two
      groups: 1) children who underwent hip joint ultrasound during both U2 and U3 and
      2) children who were first screened at the U3 stage. Of the 49 out of 54 neonates
      where the ultrasound findings were positive at the U2 examination the hip joint
      was matured in 32 children at U3 (4-8 weeks), 11 children had to be treated for 8
      12 weeks 5 children were treated for over 3 months and1 child needed surgical
      correction. CONCLUSION: The early diagnosis of hip maturation disorders and joint
      dysplasia facilitates early implementation of effective treatment. At our clinic
      over 60 % of the infants underwent the U2 check up and, given a pathological
      finding, could undergo early treatment. It was possible to successfully treat 78
      % of these children with a Tubingen hip flexion splint in just 4-8 weeks. In
      contrast, infants who were first examined at the U3 stage needed treatment for 4
      12 months. In our opinion, early diagnosis at the age of 3-10 days should be
      carried out for all newborns.

PMID- 24464332
TI  - [Conservative treatment of chronic tendinopathies].
AB  - The majority of insertional and noninsertional tendinopathy cases are associated
      with repetitive or overuse injuries. Certain tendons are particularly vulnerable
      to degenerative pathology; these include the Achilles and patella tendon, the
      rotator cuff, and forearm extensors/flexors. Disorders of these tendons are often
      chronic and can be difficult to manage successfully in the long term. Eccentric
      exercise has the strongest evidence of therapeutic efficacy. Extracorporeal shock
      wave treatment, sclerosing agents as well as nitric oxide patches show promising
      early results but require long-term studies. Corticosteroid and nonsteroidal
      antiinflammatory medications have not been shown to be effective except for
      temporary pain relief for rotator cuff tendinopathy. Platelet-rich plasma
      injections show encouraging short-term results. 

PMID- 24464333
TI  - Impact of Robertsonian translocation on meiosis and reproduction: an impala
      (Aepyceros melampus) model.
AB  - The captive bred animal populations showing centric fusion polymorphism can serve
      as a model for analysis of the impact of the rearrangement on meiosis and
      reproduction. The synapsis of homologous chromosomes and the frequency and
      distribution of meiotic recombination events were studied in pachytene
      spermatocytes of captive bred male impalas (Aepyceros melampus) polymorphic for
      der(14;20) by immunofluorescent analysis and fluorescence in situ hybridization.
      The chromosomes 14 and 20 involved in the centric fusion were significantly
      shorter due to the loss of sat I repeats indicating ancient origin of the
      rearrangement. The fused chromosome and the normal acrocentric chromosomes 14 and
      20 formed trivalent in pachynema which showed either protruding proximal ends of
      the acrocentric chromosomes or single axis with synaptic adjustment in the
      pericentromeric region. There was no significant difference in the number of
      recombination events per cell between the group of translocation heterozygotes
      and the animals with normal karyotype. A significant reduction in the number of
      recombination events was observed in the trivalent chromosomes compared to the
      normal chromosomes 14 and 20. The level of the recombination reduction was
      related to the trivalent configuration. The centric fusion der(14;20) was not
      apparently demonstrated by any spermatogenic defects or reproductive impairment
      in heterozygous impalas. However, the high incidence of the chromosomal
      polymorphism within the captive bred population shows the importance of
      cytogenetic examinations in captive breeding and wildlife conservation programs,
      especially in the case of reintroduction of the endangered species. 

PMID- 24464334
TI  - Castration-induced changes in microRNA expression profiles in subcutaneous
      adipose tissue of male pigs.
AB  - MicroRNAs (miRNAs) are class of molecular regulators found to participate in
      numerous biological processes, such as adipogenesis and obesity in mammals. To
      determine the roles of miRNAs involved in castration-induced body fatness, we
      investigated the different miRNA expression patterns in subcutaneous adipose
      tissue between intact and castrated male pigs. Our results showed that castration
      led to decrease serum testosterone but increase serum Leptin levels (P < 0.01).
      Moreover, castration also increased adipocyte size, body fat content and backfat
      thickness in male pigs (P < 0.01). Meanwhile, miRNA expression profiles in
      adipose tissue were changed by castration, and 18 miRNAs were considered as the
      differentially expressed candidates between intact and castrated male pigs.
      Furthermore, functional analysis indicated that the differential expressed miRNAs
      and their target genes are involved in the regulation of fatty acid metabolism.
      In brief, our present study provides a comprehensive view on how miRNAs works in
      subcutaneous adipose tissue with castration. These results suggested that miRNAs
      might play an important role in the castration-induced fat deposition in male
      pigs. 

PMID- 24464335
TI  - [Perihilar cholangiocarcinoma (Klatskin tumor)].
AB  - Perihilar cholangiocarcinoma or Klatskin tumors are a rare entity arising from
      the extrahepatic bile duct bifurcation. Considering the close anatomical
      relationship of the bile duct bifurcation with the portal vein bifurcation and
      hepatic arteries, surgical treatment is demanding. With an incidence of only 2-4
      cases/100,000 population/year patients should be referred to a specialized
      center. The tumors are usually poorly differentiated adenocarcinomas growing
      diffusely along the duct and also the perineural sheath. Only radical surgery
      offers a curative option and currently surgical strategy usually consists of en
      bloc resection of the bile duct, extended liver resection and portal vein
      resection. Proximal and lateral safety margin R0 resections are technically very
      demanding procedures because of the local anatomy. 

PMID- 24464337
TI  - [Gangrenous appendicitis?].

PMID- 24464336
TI  - [Quality of life and visceral surgery].
AB  - Quality of life (QOL) is becoming more and more relevant in clinical research. An
      increasing number of publications each year confirmed this. The aim of this
      review is to summarize current data of QOL after surgical procedures. The results
      are represented by two examples each of malignant and benign diseases. The
      evaluation of QOL for patients with cancer is only possible with respect to the
      prognosis. Prospective randomized trials comparing laparoscopic and open surgery
      for early gastric cancer are only available from Asia. Data from the USA show
      that the QOL after gastrectomy was worse regardless of the surgical procedure.
      During the next 6 months the QOL improved but about one third of the patients had
      severe impairment during longer follow-up periods. Patients with R1 resection of
      pancreatic cancer showed only a slightly better prognosis but significantly
      better QOL compared to patients without resection. The results for the various
      procedures of cholecystectomy or hernia repair are not always consistent.

PMID- 24464338
TI  - Diabetes in long-term care facilities.
AB  - With the aging of the population and longer life expectancies, the prevalence of
      population with multiple chronic medical conditions has increased. Difficulty
      managing these conditions as people age (because of changes in physical,
      functional, or cognitive abilities and the complexity of many treatment
      regimens), has led to more individuals with multiple medical conditions admitted
      to the long-term care facilities. Older adults with diabetes residing in the long
      term facilities represent the most vulnerable of this cohort. Studies that
      specifically target diabetes management in older population are lacking and those
      that target diabetes management in the long-term care facilities are even fewer.
      The lack of knowledge regarding the care of the elderly residing in long-term
      care with diabetes may lead to treatment failure and higher risk of
      hyperglycemia, as well as hypoglycemia. In aging populations, hypoglycemia has
      the potential for catastrophic consequences. To avoid this, the management of
      older population with diabetes and other medical comorbidities residing in long
      term care facilities requires a more holistic approach compared with focusing on
      individual chronic disease goal achievement.

PMID- 24464339
TI  - Integrated community-healthcare diabetes interventions to reduce disparities.
AB  - Racial and ethnic minorities suffer disproportionately from diabetes-related
      morbidity and mortality. With the creation of Accountable Care Organizations
      (ACOs) under the Affordable Care Act, healthcare organizations may have an
      increased motivation to implement interventions that collaborate with community
      resources and organizations. As a result, there will be an increasing need for
      evidence-based strategies that integrate healthcare and community components to
      reduce diabetes disparities. This paper summarizes the types of community/health
      system partnerships that have been implemented over the past several years to
      improve minority health and reduce disparities among racial/ethnic minorities and
      describes the components that are most commonly integrated. In addition, we
      provide our recommendations for creating stronger healthcare and community
      partnerships through enhanced community support.

PMID- 24464341
TI  - Chemically designed Pt/PPy nano-composite for effective LPG gas sensor.
AB  - Simultaneous in situ reduction of hexachloroplatinic acid by the amine group in
      the pyrrole monomer and oxidation of pyrrole to form polypyrrole (PPy) was
      examined. The reactions were performed at various temperatures to understand the
      degree of reduction of platinum precursor as well as doping of polypyrrole with
      Pt(II) chloro-complex. Spectroscopic images revealed different morphologies for
      the Pt/PPy nano-composite prepared at various temperatures. The as-prepared
      Pt/PPy nano-composite samples were tested for their ability to sense liquefied
      petroleum gas (LPG) which resulted in excellent sensing at relatively low
      temperature. The porous nature and ohmic contact between the PPy and platinum
      nanoparticles makes the as-prepared Pt/PPy nano-composite highly useful for
      sensors as well as electronic applications.

PMID- 24464340
TI  - The potential of cell-based therapy for diabetes and diabetes-related vascular
      complications.
AB  - Cell therapy has enormous potential for the treatment of conditions of unmet
      medical need. Cell therapy may be applied to diabetes mellitus in the context of
      beta cell replacement or for the treatment of diabetic complications. A large
      number of cell types including hematopoietic stem cells, mesenchymal stem cells,
      umbilical cord blood, conditioned lymphocytes, mononuclear cells, or a
      combination of these cells have been shown to be safe and feasible for the
      treatment of patients with diabetes mellitus. The first part of this review
      article will focus on the current perspective of the role of embryonic stem cells
      and inducible pluripotent stem cells for beta cell replacement and the current
      clinical data on cell-based therapy for the restoration of normoglycemia. The
      second part of this review will highlight the therapeutic role of MSCs in islet
      cells cotransplantation and the management of diabetes related vascular
      complications.

PMID- 24464342
TI  - Serum antibody titers against hepatitis C virus and postoperative intrahepatic
      recurrence of hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the seventh most common cancer and
      the third leading cause of cancer deaths worldwide. Hepatitis C virus (HCV)
      infection is a major risk factor for HCC recurrence after curative resection.
      This study evaluated anti-HCV antibody (Ab) titer as a prognostic indicator of
      HCC recurrence after curative hepatic resection. METHODS: A total of 82 patients
      with HCC (anti-HCV Ab positive and hepatitis B surface antigen negative) who
      underwent curative hepatic resection were evaluated. Anti-HCV Ab titers were
      measured using a third-generation enzyme immunoassay, and patients were divided
      into high (n = 41) and low (n = 41) titer groups to compare their
      clinicopathological characteristics and disease-free survival. Univariate and
      multivariate analyses were conducted to identify risk factors for early or late
      recurrence. RESULTS: Multivariate analysis showed that anti-HCV Ab titer and
      vascular invasion were independent prognostic factors of disease-free survival
      [odds ratio (OR) 1.9, p = 0.03, and OR 1.8, p = 0.04, respectively]. Subgroup
      analysis identified only vascular invasion as an independent prognostic factor
      for early recurrences that were considered residual intrahepatic metastases.
      Subgroup analysis identified anti-HCV Ab titer and fibrosis grade as independent
      prognostic factors of late recurrences that were considered to be metachronous
      multicentric liver carcinogenesis (OR 4.8, p = 0.04, and OR 5.2, p = 0.03,
      respectively). DISCUSSION: Anti-HCV Ab titer is a predictive factor for HCC
      recurrence, especially the risk of late recurrence due to multicentric
      carcinogenesis. Prevention of liver carcinogenesis after hepatic resection for
      HCC might be appropriate for patients with high anti-HCV Ab titers.

PMID- 24464344
TI  - Self-assembly of mesoporous nanotubes assembled from interwoven ultrathin
      birnessite-type MnO2 nanosheets for asymmetric supercapacitors.
AB  - Porous nanotubes comprised of MnO2 nanosheets were fabricated with a one-pot
      hydrothermal method using polycarbonate membrane as the template. The diameter
      and thickness of nanotubes can be controlled by choice of the membrane pore size
      and the chemistry. The porous MnO2 nanotubes were used as a supercapacitor
      electrode. The specific capacitance in a three-electrode system was 365 F g(-1)
      at a current density of 0.25 A g(-1) with capacitance retention of 90.4% after
      3000 cycles. An asymmetric supercapacitor with porous MnO2 nanotubes as the
      positive electrode and activated graphene as the negative electrode yielded an
      energy density of 22.5 Wh kg(-1) and a maximum power density of 146.2 kW kg(-1);
      these values exceeded those reported for other MnO2 nanostructures. The
      supercapacitor performance was correlated with the hierarchical structure of the
      porous MnO2 nanotubes.

PMID- 24464343
TI  - Thoracopleuropneumonectomy with riblike reconstruction for recurrent thoracic
      sarcomas.
AB  - BACKGROUND: Large intrathoracic tumors may occasionally present with massive
      infiltration of the lung and chest wall that would require pneumonectomy and
      total removal of the rib cage to obtain radical surgical excision, but this
      operation carries a prohibitive risk of death for cardiopulmonary failure in the
      absence of adequate chest wall reconstruction. METHODS: We report here four
      consecutive cases of thoracopleuropneumonectomy (TPP) with en-bloc resection of
      the entire lung, chest wall, and diaphragm and immediate riblike reconstruction
      for recurrent thoracic sarcomas. Patients had undergone the initial thoracic
      surgical resection with curative intent 2-14 years before TPP. There was no
      postoperative mortality, and all patients were alive and free of disease 8-21
      months after TPP. RESULTS: To our knowledge, this is the first report in the
      medical literature of such an extensive operation, demonstrating technical
      feasibility, tolerability, and efficacy of one-stage resection and reconstruction
      by a semirigid three-dimensional riblike prosthesis modeled on a human-derived
      aluminum cast. CONCLUSIONS: Selected patients with advanced low-intermediate
      thoracic sarcomas are the ideal candidates for this extreme procedure, to
      maximize the chance of long-term tumor control and possibly cure.

PMID- 24464345
TI  - The dialogical dance: self, identity construction, positioning and embodiment in
      tango dancers.
AB  - Argentine tango is a complex phenomenon, involving music, dancing and lifestyle,
      today practiced by hundreds of thousands of people worldwide. This is already a
      good reason for psychology to make it an object of study. Besides, studying tango
      could also help to develop a dialogical way of theorizing and a dialogical
      methodology, taking into account both the genetic historical and eso-systemic
      dimensions and the individual experiencing. As any other product of human psyche,
      tango creates an universal and abstract representation of life starting from very
      situated and individual acts. Such institutionalized representation, which is at
      the same time epistemological, ethical and aesthetical, becomes a tradition -that
      is the framework distanced from the individual immediate experience- within which
      the meaning of the experiences to be make sense in return. To illustrate this
      epistemological and methodological stance, a history of the development of tango
      as dialogical social object first is sketched. Then, an ethnographic study about
      the Self actuation in a community of Italian tango dancers is presented. Results
      show how participants construct and actuate their identities in a dialogue
      between their I-positions inside and outside tango community. 

PMID- 24464346
TI  - Challenges to achievement of metal sustainability in our high-tech society.
AB  - Achievement of sustainability in metal life cycles from mining of virgin ore to
      consumer and industrial devices to end-of-life products requires greatly
      increased recycling rates and improved processing of metals using conventional
      and green chemistry technologies. Electronic and other high-tech products
      containing precious, toxic, and specialty metals usually have short lifetimes and
      low recycling rates. Products containing these metals generally are incinerated,
      discarded as waste in landfills, or dismantled in informal recycling using crude
      and environmentally irresponsible procedures. Low recycling rates of metals
      coupled with increasing demand for high-tech products containing them necessitate
      increased mining with attendant environmental, health, energy, water, and carbon
      footprint consequences. In this tutorial review, challenges to achieving metal
      sustainability, including projected use of urban mining, in present high-tech
      society are presented; health, environmental, and economic incentives for various
      government, industry, and public stakeholders to improve metal sustainability are
      discussed; a case for technical improvements, including use of molecular
      recognition, in selective metal separation technology, especially for metal
      recovery from dilute feed stocks is given; and global consequences of continuing
      on the present path are examined. 

PMID- 24464347
TI  - Management of cesarean scar pregnancy with suction curettage: a report of four
      cases and review of the literature.
AB  - PURPOSE: To present the outcomes of four cases of cesarean scar pregnancy treated
      with suction curettage. METHODS: Four patients were ultrasonographically
      diagnosed with cesarean scar pregnancies treated with suction curettage in a
      tertiary care center. RESULTS: Serum beta-human chorionic gonadotropin levels
      ranged between 1,681 and 15,573 mU/mL, gestational sac diameter measured from 10
      to 24 mm and scar thickness was between 4.7 and 6.8 mm. All patients underwent
      suction curettage under general anesthesia with transabdominal ultrasonography
      guidance. No complications were observed during or after operation. CONCLUSION:
      Suction curettage is a viable alternative for conservative treatment in selected
      cases of patients who are diagnosed with CSP early in gestation and who have a
      myometrial thickness of more than 4.5 mm.

PMID- 24464348
TI  - Simulation-based training in obstetrics.

PMID- 24464350
TI  - Physiological intestinal oxygen modulates the Caco-2 cell model and increases
      sensitivity to the phytocannabinoid cannabidiol.
AB  - The Caco-2 cell model is widely used as a model of colon cancer and small
      intestinal epithelium but, like most cell models, is cultured in atmospheric
      oxygen conditions (~21%). This does not reflect the physiological oxygen range
      found in the colon. In this study, we investigated the effect of adapting the
      Caco-2 cell line to routine culturing in a physiological oxygen (5%) environment.
      Under these conditions, cells maintain a number of key characteristics of the
      Caco-2 model, such as increased formation of tight junctions and alkaline
      phosphatase expression over the differentiation period and maintenance of barrier
      function. However, these cells exhibit differential oxidative metabolism,
      proliferate less and become larger during differentiation. In addition, these
      cells were more sensitive to cannabidiol-induced antiproliferative actions
      through changes in cellular energetics: from a drop of oxygen consumption rate
      and loss of mitochondrial membrane integrity in cells treated under atmospheric
      conditions to an increase in reactive oxygen species in intact mitochondria in
      cells treated under low-oxygen conditions. Inclusion of an additional
      physiological parameter, sodium butyrate, into the medium revealed a cannabidiol
      induced proliferative response at low doses. These effects could impact on its
      development as an anticancer therapeutic, but overall, the data supports the
      principle that culturing cells in microenvironments that more closely mimic the
      in vivo conditions is important for drug screening and mechanism of action
      studies. 

PMID- 24464351
TI  - Establishment and characterization of three new cell lines from the embryonic
      tissue of Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae).
AB  - The establishment of new insect cell lines plays important roles in the
      researches of insect pathology, insect toxicology, insecticide screening and
      activity assay, etc. Using embryos of Holotrichia oblita Faldermann (Coleoptera:
      Scarabaeidae) as materials, this study describes the establishment of three cell
      lines designated as QAU-Ho-E-3 (Ho-3), QAU-Ho-E-4 (Ho-4), and QAU-Ho-E-6 (Ho-6),
      respectively. Currently, the three cell lines have been passaged more than 50
      times in the TNM-FH insect cell medium containing 10% fetal bovine serum (FBS).
      All of them showed adherent growth. The majority of Ho-3 cells are spindle
      shaped, with a size of 24.35 +/- 5.29 * 11.56 +/- 1.67 MUm. The Ho-4 cells were
      either spindle-shaped or oblong, with a size of 38.07 +/- 8.57 * 17.62 +/- 2.48
      MUm. The Ho-6 cells were primarily round in shape with a diameter of 14.54 +/-
      1.96 MUm. The Ho-3 and Ho-4 cell lines contained 20 chromosomes (i.e., diploid,
      2n = 20) at passages 14 and 45. The Ho-6 cell line contained 20 chromosomes
      (i.e., diploid, 2n = 20) at passage 14 but 40 chromosomes (i.e., polyploidy, 4n =
      40) at passage 45. The results of random amplified polymorphic DNA (RAPD)
      analysis showed that the RAPD fingerprint of the three cell lines was consistent
      with that of H. oblita eggs, but clearly different from that of BTI-Tn5B1-4 and
      Sf-9 cells, demonstrating that the three cell lines Ho-3, Ho-4, and Ho-6 are H.
      oblita cell lines. The results of the growth curve test showed that the
      population doubling times of Ho-3, Ho-4, and Ho-6 were 101.1, 105.2, and 83.6 h,
      respectively. The viral infection assay indicated that these H. oblita cell lines
      were not permissive to infection by Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) or Bombyx mori nucleopolyhedrovirus (BmNPV).

PMID- 24464349
TI  - A novel variant in the 3' UTR of human SCN1A gene from a patient with Dravet
      syndrome decreases mRNA stability mediated by GAPDH's binding.
AB  - Mutations in the SCN1A gene-encoding voltage-gated sodium channel alpha-I subunit
      (Nav1.1) cause various spectrum of epilepsies including Dravet syndrome (DS), a
      severe and intractable form. A large number of SCN1A mutations identified from
      the DS patients lead to the loss of function or truncation of Nav1.1 that result
      in a haploinsufficiency effects, indicating that the exact expression level of
      SCN1A should be essential to maintain normal brain function. In this study, we
      have identified five variants c.*1025T>C, c.*1031A>T, c.*1739C>T, c.*1794C>T and
      c.*1961C>T in the SCN1A 3' UTR in the patients with DS. The c.*1025T>C,
      c.*1031A>T and c.*1794C>T are conserved among different species. Of all the five
      variants, only c.*1794C>T is a novel variant and alters the predicted secondary
      structure of the 3' UTR. We also show that glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) only binds to the 3' UTR sequence containing the mutation
      allele 1794U but not the wild-type allele 1794C, indicating that the mutation
      allele forms a new GAPDH-binding site. Functional analyses show that the variant
      negatively regulates the reporter gene expression by affecting the mRNA stability
      that is mediated by GAPDH's binding, and this phenomenon could be reversed by
      shRNA-induced GAPDH knockdown. These findings suggest that GAPDH and the 3'-UTR
      variant are involved in regulating SCN1A expression at post-transcriptional
      level, which may provide an important clue for further investigating on the
      relationship between 3'-UTR variants and SCN1A-related diseases. 

PMID- 24464352
TI  - Differential time preferences for money and quality of life.
AB  - BACKGROUND: This study provides an empirical investigation into differential time
      preferences between money and quality of life. Thus far, time preference
      investigations in health have mostly involved life-years gained and lives saved.
      However, the quality-adjusted life-year, which is recommended by several bodies,
      is a multiplicative measure of life duration and quality of life. To our
      knowledge, our study is the first to follow this approach specifically for
      quality of life. METHODS: A questionnaire was developed to elicit time
      preferences for quality of life and for money, and it was distributed to a
      representative sample of the Dutch population. We also investigated the impact of
      population characteristics, such as current health state, optimistic/pessimistic
      future views or gender, on time preferences. RESULTS: We found that discount
      rates for both money and quality of life decrease with increasing time of delay,
      with rates of the former being consistently at least two times higher than those
      of the latter. Similar trends in time preferences were observed across the
      subgroups, with the exception of the relatively high education subgroup.
      CONCLUSION: In agreement with the results of other studies, our empirically
      derived discount rates are higher than the rates featured in national guidelines
      for health care economic assessment. Our empirical study adds to the evidence for
      differential discounting, both with regards to money and health, as well as in
      time.

PMID- 24464353
TI  - Efficiency of plant growth-promoting P-solubilizing Bacillus circulans CB7 for
      enhancement of tomato growth under net house conditions.
AB  - P-solubilizing bacterial isolate CB7 isolated from apple rhizosphere soil of
      Himachal Pradesh, India was identified as Bacillus circulans on the basis of
      phenotypic characteristics, biochemical tests, fatty acid methyl esters analysis,
      and 16S rRNA gene sequence. The isolate exhibited plant growth-promoting traits
      of P-solubilization, auxin, 1-aminocyclopropane-1-carboxylate deaminase activity,
      siderophore, nitrogenase activity, and antagonistic activity against Dematophora
      necatrix. In vitro studies revealed that P-solubilization and other plant growth
      promoting traits were dependent on the presence of glucose in PVK medium and
      removal of yeast extract had no significant effect on plant growth-promoting
      traits. Plant growth-promoting traits of isolate CB7 were repressed in the
      presence of KH2 PO4 . P-solubilization activity was associated with the release
      of organic acids and a drop in the pH of the Pikovskaya's medium. HPLC analysis
      detected gluconic and citric acid as major organic acids in the course of P
      solubilization. Remarkable increase was observed in seed germination (22.32%),
      shoot length (15.91%), root length (25.10%), shoot dry weight (52.92%) and root
      dry weight (31.4%), nitrogen (18.75%), potassium (57.69%), and phosphorus
      (22.22%) content of shoot biomass over control. These results demonstrate that
      isolate CB7 has the promising PGPR attributes to be developed as a biofertilizer
      to enhance soil fertility and promote plant growth. 

PMID- 24464354
TI  - Aggression and aspects of impulsivity in wild-type rats.
AB  - Aggression is closely related to impulsive behavior both in humans and in
      animals. To avoid potential negative consequences, aggressive behavior is kept in
      control by strong inhibitory mechanisms. Failure of these inhibitory mechanisms
      results in violent behavior. In the present experiments, we investigated whether
      aggressive behavior is related to impulsive behavior. Furthermore, we
      investigated if violent behavior can be distinguished from "normal" aggressive
      behavior in terms of impulsivity levels. We used rats of the wild-type Groningen
      strain, rats of this strain differ widely in their level of offensive aggression
      expressed toward an unfamiliar intruder male, ranging from no aggression at all
      to very high levels of intense and sometimes violent behavior. Violent behavior
      was displayed by some of the animals that were given repeated winning experience.
      We used behavioral performance in an unpredictable operant conditioning paradigm
      for food reinforcement (variable interval 15) and performance in a differential
      reinforcement of low rate (DRL-60s) responding as determinants for impulsivity.
      We predicted that offensive aggression is correlated with behavioral flexibility
      measured by the VI-15 procedure and that aggressive behavior is characterized by
      low behavioral inhibition on the DRL task. In addition we expected that violent
      animals would be characterized by extremely low levels of behavioral inhibition
      on the DRL task. We showed that the level of offensive aggression indeed
      positively correlated with VI-15 performance. In addition, we showed that
      behavioral performance on the DRL procedure is similar in low and high aggressive
      rats. However, violent animals can be dissociated by a lower efficiency of lever
      pressing on a DRL-60s schedule of reinforcement.

PMID- 24464355
TI  - Phase 1 study of pazopanib alone or combined with lapatinib in Japanese patients
      with solid tumors.
AB  - PURPOSE: A phase 1 study of pazopanib alone or in combination with lapatinib was
      conducted to assess the safety, tolerability, and pharmacokinetics of these oral
      tyrosine kinase inhibitors in Japanese patients with solid tumors. METHODS: In
      part A (monotherapy), 7 patients initially received pazopanib 800 mg/day, the
      recommended dose for non-Japanese patients. Then, 3 patients received pazopanib
      400 mg/day on day 1 followed by 800 mg/day from day 2 onward. Three other
      patients received pazopanib 1,000 mg/day. In part B (combination therapy), 17
      patients received pazopanib plus lapatinib (pazopanib/lapatinib) at once-daily
      doses of 400/1,000 mg (4 patients), 800/1,000 mg (3 patients), 400/1,500 mg (3
      patients), and then 600/1,250 mg (7 patients). RESULTS: There was no dose
      limiting toxicity during the study. In part A, most drug-related adverse events
      were grade 2 or lower, including neutropenia/neutrophil count decreased,
      thrombocytopenia/platelet count decreased, diarrhea, hypertension, aspartate
      aminotransferase increased, and lipase increased. In part B, rash, decreased
      appetite, and serum thyroid-stimulating hormone increased also occurred. In all
      dose groups, the plasma concentrations after multiple doses of pazopanib exceeded
      the target trough concentration for inhibition of vascular endothelial growth
      factor receptor-2 activity (20 MUg/mL). CONCLUSIONS: The pharmacokinetic profiles
      of pazopanib and lapatinib in Japanese patients were not apparently different
      from those reported in non-Japanese patients. There were no consistent trends in
      pharmacokinetic drug interactions between pazopanib and lapatinib. Pazopanib
      monotherapy at 800 and 1,000 mg once daily and pazopanib plus lapatinib once
      daily at any doses studied were well tolerated in Japanese patients.

PMID- 24464356
TI  - Intraperitoneal paclitaxel induces regression of peritoneal metastasis partly by
      destruction of peripheral microvessels.
AB  - PURPOSE: Intraperitoneal (IP) administration of paclitaxel (PTX) can enable
      direct infiltrate of high amount of PTX into peritoneal nodules and elicit
      remarkable clinical responses against peritoneal metastases. In this study, we
      examined the mechanisms leading to tumor shrinkage after IP PTX. METHODS: We
      compared the microscopic features of peritoneal metastases before and after IP
      PTX in surgically removed human samples, as well as in a murine xenograft model
      using immunohistochemistry. RESULTS: We found that many microvessels exist in the
      peripheral areas of metastatic nodules in human samples before treatment.
      However, peripheral vessels were greatly reduced in number, and luminal
      obstructions were observed in lesions showing complete response after
      chemotherapy including IP PTX. Similar changes were observed in peripheral
      vessels of peritoneal tumors in MKN45-inoculated nude mice treated with IP-PTX.
      Moreover, pimonidazole staining revealed that highly hypoxic regions were
      produced by IP PTX at the tumor periphery. CONCLUSIONS: These findings strongly
      suggest that the remarkable efficacy of IP PTX in the treatment of peritoneal
      metastases is, at least in part, dependent on the destruction of peripheral
      microvessels by exposure to infiltrated PTX.

PMID- 24464357
TI  - Diagnostic significance of high sensitivity troponin in diagnosis of blunt
      cardiac injury.

PMID- 24464358
TI  - Erratum to: Early postoperative prophylactic noninvasive ventilation after major
      lung resection in COPD patients: a randomized controlled trial.

PMID- 24464359
TI  - A comparison of alternating current and direct current electrospray ionization
      for mass spectrometry.
AB  - A series of studies comparing the performance of alternating current electrospray
      ionization (AC ESI) mass spectrometry (MS) and direct current electrospray
      ionization (DC ESI) MS have been conducted, exploring the absolute signal
      intensity and signal-to-background ratios produced by both methods using caffeine
      and a model peptide as targets. Because the high-voltage AC signal was more
      susceptible to generating gas discharges, the operating voltage range of AC ESI
      was significantly smaller than that for DC ESI, such that the absolute signal
      intensities produced by DC ESI at peak voltages were one to two orders of
      magnitude greater than those for AC ESI. Using an electronegative nebulizing gas,
      sulfur hexafluoride (SF6), instead of nitrogen (N2) increased the operating range
      of AC ESI by ~50%, but did not appreciably improve signal intensities. While DC
      ESI generated far greater signal intensities, both ionization methods produced
      comparable signal-to-background noise, with AC ESI spectra appearing
      qualitatively cleaner. A quantitative calibration analysis was performed for two
      analytes, caffeine and the peptide MRFA. AC ESI utilizing SF6 outperforms all
      other techniques for the detection of MRFA, producing chromatographic limits of
      detection nearly one order of magnitude lower than that of DC ESI utilizing N2,
      and one-half that of DC ESI utilizing SF6. However, DC ESI outperforms AC ESI for
      the analysis of caffeine, indicating that improvements in spectral quality may
      benefit certain compounds or classes of compounds, on an individual basis.

PMID- 24464360
TI  - Novel drugs targeting transthyretin amyloidosis.
AB  - Transthyretin amyloidosis (ATTR) is either a hereditary disease related to a
      mutation in the transthyretin gene that leads to neuropathy and/or cardiomyopathy
      or an acquired disease of the elderly that leads to restrictive cardiomyopathy.
      The prevalence of this disease is higher than once thought and awareness is
      likely to increase amongst physicians and in particular cardiologists. Until
      recently there have been no treatment options for this disease except to treat
      the heart failure with diuretics and the neuropathy symptomatically. However,
      there are several emerging pharmacologic therapies designed to slow or stop the
      progression of ATTR. This article reviews novel therapeutic drugs that work at
      different points in the pathogenesis of this disease attempting to change its
      natural history and improve outcomes. 

PMID- 24464362
TI  - Comparing national cancer registries: The National Cancer Data Base (NCDB) and
      the Surveillance, Epidemiology, and End Results (SEER) program.

PMID- 24464361
TI  - Presynaptic membrane receptors in acetylcholine release modulation in the
      neuromuscular synapse.
AB  - Over the past few years, we have studied, in the mammalian neuromuscular junction
      (NMJ), the local involvement in transmitter release of the presynaptic muscarinic
      ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and
      trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during
      development and in the adult. At any given moment, the way in which a synapse
      works is largely the logical outcome of the confluence of these (and other)
      metabotropic signalling pathways on intracellular kinases, which phosphorylate
      protein targets and materialize adaptive changes. We propose an integrated
      interpretation of the complementary function of these receptors in the adult NMJ.
      The activity of a given receptor group can modulate a given combination of
      spontaneous, evoked, and activity-dependent release characteristics. For
      instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh
      (an A1 R action) and protect synapse function, because stimulation with adenosine
      reduces the magnitude of depression during repetitive activity. The overall
      outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output
      of ACh, save synapse function by decreasing the extent of evoked release (mainly
      an M2 action), and reduce depression. We have also identified several links among
      P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs
      and observed that the muscarinic group has to operate correctly if the
      tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and
      vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs
      operating normally.

PMID- 24464363
TI  - Carbohydrate coated, folate functionalized colloidal graphene as a nanocarrier
      for both hydrophobic and hydrophilic drugs.
AB  - Although graphene based drug delivery has gained significant recent interest, the
      synthesis of colloidal graphene based nanocarriers with high drug loading
      capacities and with targeting ligands at the outer surface is a challenging
      issue. We have synthesized carbohydrate coated and folate functionalized
      colloidal graphene which can be used as a nanocarrier for a wide variety of
      hydrophobic and hydrophilic drugs. The synthesized colloidal graphene is loaded
      with paclitaxol, camptothecin, doxorubicin, curcumin and used for their targeted
      delivery to cancer cells. We demonstrate that this drug loaded functional
      graphene nanocarrier can successfully deliver drugs into target cells and offers
      an enhanced therapeutic performance. The reported approach can be extended to the
      cellular delivery of other hydrophobic and hydrophilic drugs and the simultaneous
      delivery of multiple drugs. 

PMID- 24464364
TI  - Treatment of obesity with the resveratrol-enriched rice DJ-526.
AB  - Obesity is the most prevalent disease in the world which poses a serious risk for
      various chronic diseases. However, currently there are not any therapeutic agents
      that reduce body weight without causing serious side effects. In order to prevent
      and/or treat obesity and related diseases through a nutraceutical approach, we
      created a resveratrol-enriched transgenic rice accumulating 1.4 MUg/g of
      resveratrol in its grain, DJ-526. Feeding of mice with the resveratrol-enriched
      rice DJ-526 showed excellent anti-obesity effect with reduction of body weights
      and abdominal fat volumes compared to the control by 20.0% and 31.3%,
      respectively. Also, the consumption of the resveratrol-enriched rice DJ526
      significantly improved the blood lipid profiles and glucose levels in the animal
      experiments. Our resveratrol-enriched rice DJ-526 rice could provide both safe
      and convenient way for people with obesity and related diseases without major
      change of lifestyle or unwanted side effects from medication.

PMID- 24464365
TI  - The influence of achievement before, during and after medical school on physician
      job satisfaction.
AB  - In this longitudinal study, we investigated the relationship between physicians'
      prior achievements (before, during and after medical school) and job
      satisfaction, and tested the two lines of reasoning that prior achievements
      influence job satisfaction positively or negatively, respectively. The
      participants were graduates who started their medical training in 1982 (n = 147),
      1983 (n = 154), 1992 (n = 143) and 1993 (n = 153). We operationalised job
      satisfaction as satisfaction (on a 10-point scale) with 13 cognitive, affective
      and instrumental aspects of the participants' jobs. The measures of achievement
      before, during and after medical school included pre-university grade point
      average, study progress and a residency position in the specialty of first
      choice, respectively. We included the effect of curriculum type (problem-based
      learning versus traditional), gender and years of experience as moderator
      variables. Higher achievers before and during medical school were more satisfied
      about their income (beta = .152, p < .01 and beta = .149, p < .05), but less
      satisfied with their opportunities for personal development (beta = -.159, p <
      .05). High achievers after medical school were more satisfied with professional
      accomplishments (beta = .095, p < .05), with appreciation from support personnel
      (beta = .154, p < .01) and from patients (beta = .120, p < .05). Effect sizes
      were small. Prior achievements influenced job satisfaction. The direction of the
      influences depended on the job satisfaction aspect in question, which indicates
      that it is important to distinguish between aspects of job satisfaction. To
      optimize job satisfaction of high achievers, it is important for graduates to
      obtain their preferred specialty. Furthermore, it is vital to provide them with
      enough opportunities for further development.

PMID- 24464366
TI  - Outcome based education enacted: teachers' tensions in balancing between student
      learning and bureaucracy.
AB  - This paper reports on how teachers within health sciences education translate
      outcome-based education (OBE) into practice when they design courses. The study
      is an empirical contribution to the debate about outcome- and competency-based
      approaches in health sciences education. A qualitative method was used to study
      how teachers from 14 different study programmes designed courses before and after
      OBE was implemented. Using an interpretative approach, analysis of documents and
      interviews was carried out. The findings show that teachers enacted OBE either to
      design for more competency-oriented teaching-learning, or to further detail
      knowledge and thus move towards reductionism. Teachers mainly understood the
      outcome-based framework as useful to support students' learning, although the
      demand for accountability created tension and became a bureaucratic hindrance to
      design for development of professional competence. The paper shows variations of
      how teachers enacted the same outcome-based framework for instructional design.
      These differences can add a richer understanding of how outcome- or competency
      based approaches relate to teaching-learning at a course level.

PMID- 24464368
TI  - Comparative effects of sediment versus aqueous polychlorinated biphenyl (PCB)
      exposure on benthic and planktonic invertebrates.
AB  - Polychlorinated biphenyls (PCBs) are an environmental concern because of their
      adverse effects on humans and wildlife, and understanding the contribution of
      various matrices (i.e., sediment and water) to PCB exposure on aquatic
      communities is critical for successful remediation of impacted sites. The present
      study examined the toxicity of different routes of PCB exposure in aquatic
      invertebrates. In complementary laboratory and field experiments, the authors
      compared the effects of aqueous versus sedimentary exposure of PCBs on
      invertebrates. In laboratory bioassays, the planktonic Daphnia pulex and benthic
      Chironomus dilutus exhibited significant mortality when exposed to PCB
      contaminated (1100 ug/g) sediment (p = 0.03 and p < 0.01, respectively). In field
      experiments, adult Dreissena bugensis were placed in cages along a depth gradient
      at a reference site and a PCB-impacted site in St. Clair Shores, Michigan, USA.
      Mussels experienced significantly greater mortality (p < 0.001) when placed in
      close proximity to impacted-site sediments compared with reference sediments.
      After 7 d, 94% of D. bugensis survived at the reference site compared with only
      57% surviving at the impacted site. In addition, D. bugensis at the impacted site
      experienced significantly less mortality at the water surface (p < 0.001)
      compared to those near the sediment. The present study demonstrates the
      importance of evaluating toxicity at the sediment-water interface.

PMID- 24464374
TI  - Lords debate welfare at slaughter.

PMID- 24464367
TI  - Transgenic plants that express the phytoplasma effector SAP11 show altered
      phosphate starvation and defense responses.
AB  - Phytoplasmas have the smallest genome among bacteria and lack many essential
      genes required for biosynthetic and metabolic functions, making them
      unculturable, phloem-limited plant pathogens. In this study, we observed that
      transgenic Arabidopsis (Arabidopsis thaliana) expressing the secreted Aster
      Yellows phytoplasma strain Witches' Broom protein11 shows an altered root
      architecture, similarly to the disease symptoms of phytoplasma-infected plants,
      by forming hairy roots. This morphological change is paralleled by an
      accumulation of cellular phosphate (Pi) and an increase in the expression levels
      of Pi starvation-induced genes and microRNAs. In addition to the Pi starvation
      responses, we found that secreted Aster Yellows phytoplasma strain Witches' Broom
      protein11 suppresses salicylic acid-mediated defense responses and enhances the
      growth of a bacterial pathogen. These results contribute to an improved
      understanding of the role of phytoplasma effector SAP11 and provide new insights
      for understanding the molecular basis of plant-pathogen interactions. 

PMID- 24464369
TI  - Effects of compound Shenhua tablet on renal tubular Na+-K+-ATPase in rats with
      acute ischemic reperfusion injury.
AB  - OBJECTIVE: To observe the effect of Compound Shenhua Tablet (, SHT) on the sodium
      potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal
      tubular epithelial cells of rats with acute ischemic reperfusion and to
      investigate the mechanisms underlying the effects of SHT on renal ischemic
      reperfusion injury (RIRI). METHODS: Fifty male Wistar rats were randomly divided
      into the sham surgery group, model group, astragaloside group [150 mg/(kg.d)],
      SHT low-dose group [1.5 g/(kg.d)] and SHT high-dose group [3.0 g/(kg.d)], with 10
      rats in each group. After 1 week of continuous intragastric drug administration,
      surgery was performed to establish the model. At either 24 or 72 h after the
      surgery, 5 rats in each group were sacrificed, blood biochemistry, renal
      pathology, immunoblot and immunohistochemical examinations were performed, and
      double immunofluorescence staining was observed under a laser confocal
      microscope. RESULTS: Compared with the sham surgery group, the serum creatinine
      (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)
      K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1)
      protein level was increased in the model group after the surgery (P<0.01 or
      P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)
      K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were
      significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr,
      BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT
      high-dose group were significantly lower than those of the astragaloside group
      (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group
      were disrupted, with the distribution areas overlapping with each other and
      alternately arranged. The severity of the disruption was slightly milder in three
      treatment groups compared with that of the model group. The results of
      immunofluorescence staining showed that the SHT high-dose group had a superior
      effect as compared with the astragaloside group and the SHT low-dose group.
      CONCLUSIONS: The SHT effectively alleviated RIRI caused by ischemic reperfusion,
      promoted the recovery of the polarity of renal tubular epithelial cells, and
      protected the renal tubules. The therapeutic effects of SHT were superior to
      those of astragaloside as a single agent.

PMID- 24464375
TI  - Playing a part in the future of the profession.
AB  - Following recent changes to its governance structure, the RCVS has adopted a new
      strategy (VR, November 23, 2013, vol 173, p 484). Luke Bishop, from the
      communications team at the College, argues that there is no better time for vets
      from all backgrounds to stand for election to the RCVS Council. 

PMID- 24464377
TI  - The evolution of One Health: a decade of progress and challenges for the future.
AB  - The One Health concept is gathering momentum and, over the next 12 months,
      Veterinary Record will be publishing a series of articles to help encourage that
      process. Written by specialists in a range of fields, the articles will consider
      the meaning of One Health, the interactions between animal and human health and
      how a collaborative and interdisciplinary approach could help to solve emerging
      global problems. To set the scene, Paul Gibbs outlines the recent history of One
      Health, discusses current challenges and muses on what the future might hold. 

PMID- 24464378
TI  - Salmonella infection and carriage: the importance of dogs and their owners.

PMID- 24464379
TI  - Veterinary contribution to food production.

PMID- 24464380
TI  - Mass mortality of starlings.

PMID- 24464381
TI  - Great ape mortality study.

PMID- 24464382
TI  - Origins of 'one medicine'.

PMID- 24464384
TI  - Feasibility of a robot-assisted thoracoscopic lymphadenectomy along the recurrent
      laryngeal nerves in radical esophagectomy for esophageal squamous carcinoma.
AB  - BACKGROUND: Lymph node dissection along bilateral recurrent laryngeal nerves
      (RLNs) is an essential component of radical esophagectomy for esophageal squamous
      carcinoma. However, it is associated with significant morbidity and requires a
      great deal of skill when performed with minimally invasive surgery. METHODS:
      Between October 2010 and July 2012, 40 consecutive patients underwent a robot
      assisted thoracoscopic esophagectomy and total mediastinal lymphadenectomy. The
      lymph nodes along the dorsal side of the RLNs were removed in the initial 18
      patients (group 1), and the RLNs were skeletonized by dissection of all the lymph
      nodes and surrounding fatty tissues in the following 22 patients (group 2).
      RESULTS: All but one patient underwent a successful robot-assisted, thoracoscopic
      esophagectomy. The mean operation time was 428.6 +/- 75.0 min, and the mean robot
      console time was 186.7 +/- 52.1 min. An average of 42.6 +/- 14.1 nodes was
      retrieved, and the mean number of dissected nodes from the mediastinum and the
      RLN chains were 25.5 +/- 9.6 and 9.6 +/- 6.5, respectively. One mortality
      occurred (2.5%), and the incidences of pneumonia and RLN palsy were 12.5 and 20%,
      respectively. The mean robot console time was longer in group 2 (211.4 +/- 49.5
      min) than in group 1 (156.6 +/- 38.2 min) (p < 0.001), and group 2 had higher
      mean numbers of dissected nodes from the mediastinum (30.3 +/- 7.9 vs 19.6 +/-
      8.2; p < 0.001) and the RLN chains (13.5 +/- 5.7 vs 4.8 +/- 3.6; p < 0.001).
      Although RLN palsy was more common in group 2 (31.8 vs 5.6%; p = 0.054), all
      palsies resolved within 1 year. CONCLUSIONS: Robot-assisted thoracoscopic
      lymphadenectomy along bilateral RLNs was technically feasible and safe.
      Skeletonization of the RLNs yields more lymph nodes, but efforts should be made
      to decrease the incidence of RLN palsy.

PMID- 24464385
TI  - Postoperative pain after transvaginal cholecystectomy: single-center, double
      blind, randomized controlled trial.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has the
      potential to reduce postoperative pain. We compared postoperative pain in the
      hybrid NOTES procedure transvaginal video-assisted cholecystectomy (TVC) with
      standard conventional laparoscopic cholecystectomy (CLC). DESIGN: Single-center,
      double-blind, randomized controlled trial in a level II hospital between June
      2008 and June 2012. METHODS: Female patients, older than 18 years of age with
      symptomatic cholecystolithiasis were randomized to receive either TVC or CLC. The
      follow-up period was 7 days and the primary outcome of the study was
      postoperative pain. We hypothesized that there is no reduction of pain (Visual
      Rating Scale >=1) while resting or coughing over a 48-h period after the
      operation. Secondary outcome included wound infections, complications, and
      patient reported outcomes. Sealed envelopes with computer-generated randomization
      information were kept for allocation in theater. All patients received opaque
      wound dressing, as in standard four-trocar cholecystectomy and a vaginal
      tamponade. Theater protocol and surgical notes were kept separate after the
      procedure. RESULTS: Overall, 97 of 426 patients assessed for participation were
      randomized for either TVC or CLC. A total of 41 patients had a TVC and 51 had a
      CLC. Five patients were excluded from the analysis. There was no difference in
      age, body mass index, American Society of Anesthesiologists (ASA) grade, or
      hospital stay, but anesthetic and surgical times were significantly longer in TVC
      (p < 0.001). There was no statistical difference in postoperative pain between
      the two groups while resting or coughing. Complications included conversion to
      laparotomy, bleeding, wound infections, and re-admission. No difference in the
      rate of complications between the two groups was seen. Overall, 86 and 93% of CLC
      and TVC patients, respectively, would recommend the procedure to other patients.
      CONCLUSION: In this study, no significant difference in pain on days 1 and 2
      postoperatively between the two methods was found. The safety profile of TVC is
      comparable to CLC, and TVC patients would generally recommend this procedure to
      other patients.

PMID- 24464386
TI  - Comparison of swallowing disorder following gasless transaxillary endoscopic
      thyroidectomy versus conventional open thyroidectomy.
AB  - BACKGROUND: In conventional open thyroidectomy, it is necessary to create a sub
      platysma muscle flap in front of the strap muscle to provide working space.
      Adhesion between the flap and the strap muscle can occur after the operation,
      disrupting strap muscle movement and causing a swallowing disorder. Gasless
      transaxillary endoscopic thyroidectomy approaches the thyroid through the
      posterior of the strap muscle and does not require a sub-platysma muscle flap.
      The present study compared flap/muscle adhesion and occurrence of swallowing
      disorder following gasless transaxillary endoscopic thyroidectomy versus
      conventional open thyroidectomy. METHODS: Patients (N = 47) receiving
      thyroidectomy at the Kangbuk Samsung Medical Center, Seoul, Korea, were divided
      into two groups: group O (24 patients) underwent conventional open thyroidectomy,
      and group E (23 patients) underwent gasless transaxillary endoscopic
      thyroidectomy. The subjective Swallowing Impairment Index (SIS)-6 was used to
      evaluate the degree of post-operative swallowing disorder. Video recordings of
      swallowing movement were used to determine the contraction/relaxation (CR) ratio
      and evaluate adhesion, pre-operation, 3 days post-operation, and 1 month post
      operation. Barium videofluoroscopy was used to measure movement of the hyoid bone
      and strap muscle. RESULTS: Group O had significantly higher post-operative SIS-6
      scores than group E (p < 0.027), indicating greater swallowing disorder. The CR
      ratio increased in group O after the operation and continued to increase during 1
      month post-operation, but decreased in group E (p < 0.001). Videofluoroscopy
      showed that hyoid bone movement in group O decreased by 55.46 and 56.75% at 3
      days and 1 month post-operation, respectively, while the corresponding decreases
      in group E were 84.04 and 83.69%. CONCLUSIONS: Conventional open thyroidectomy
      allowed adhesion of the strap muscle and sub-platysma muscle flap, resulting in
      non-specific dysphagia. These complications did not occur following gasless
      transaxillary endoscopic thyroidectomy.

PMID- 24464387
TI  - Clinical management of primary aldosteronism: 2013 Practical Recommendations of
      the Italian Society of Hypertension (SIIA).
AB  - Primary aldosteronism is the most common form of endocrine hypertension and is
      highly prevalent among patients with difficult to control high blood pressure. In
      the presence of a high sodium intake primary aldosteronism carries has
      detrimental effects on the cardiovascular system, which translate into an excess
      rate of cardiovascular events. Therefore, to prevent these ominous consequences
      primary aldosteronism should be detected as early as possible and should be
      accurately diagnosed. Institution of the most appropriate treatment can lead to
      long-term cure of hypertension and to regression of the cardiovascular changes
      with a great benefit for the patients. We herein summarize the current evidence
      based practical recommendations that will help physicians to diagnose and treat
      primary aldosteronism properly. 

PMID- 24464388
TI  - India to consider raft of new compulsory licences.

PMID- 24464389
TI  - US committee calls for comments on how to share clinical trial data.

PMID- 24464390
TI  - Taking the temperature of Detroit.

PMID- 24464391
TI  - Recommendations for (18)F-fluorodeoxyglucose positron emission tomography imaging
      for cardiac sarcoidosis: Japanese Society of Nuclear Cardiology recommendations.

PMID- 24464392
TI  - Evaluation of the difference-correction effect of the gamma camera systems used
      by easy Z-score Imaging System (eZIS) analysis.
AB  - OBJECTIVE: We examined the difference of the effect by data to revise a gamma
      camera difference. The difference-correction method of the camera is incorporated
      in eZIS analysis. METHODS: We acquired single photon emission computed tomography
      (SPECT) data from the three-dimensional (3D) Hoffman brain phantom (Hoffman), the
      three-dimensional brain phantom (3D-Brain), Pool phantom (pool) and from normal
      subjects (Normal-SPECT) to investigate compensating for a difference in gamma
      camera systems. We compared SPECT counts of standard camera with the SPECT counts
      that revised the difference of the gamma camera system (camera). Furthermore, we
      compared the "Z-score map (Z-score)". To verify the effect of the compensation,
      we examined digitally simulated data designed to represent a patient with
      Alzheimer's dementia. We carried out both eZIS analysis and "Specific Volume of
      interest Analysis (SVA)". RESULTS: There was no great difference between the
      correction effect using Hoffman phantom data and that using 3D-Brain phantom
      data. Furthermore, a good compensation effect was obtained only over a limited
      area. The compensation based on the pool was found to be less satisfactory than
      any of the other compensations according to all results of the measurements
      examined in the study. The compensation based on the Normal-SPECT data resulted
      in a Z-score map (Z-score) for the result that approximated that from the
      standard camera. Therefore, we concluded that the effect of the compensation
      based on Normal-SPECT data was the best of the four methods tested. CONCLUSIONS:
      Based on eZIS analysis, the compensation using the pool data was inferior to the
      compensations using the other methods tested. Based on the results of the SAV
      analysis, the effect of the compensation using the Hoffman data was better than
      the effect of the compensation using the 3D-Brain data. By all end-point
      measures, the compensation based on the Normal-SPECT data was more accurate than
      the compensation based on any of the other three phantoms.

PMID- 24464394
TI  - Transient bilateral vestibular dysfunction caused by intoxication with low doses
      of styrene.

PMID- 24464393
TI  - Initial experience in Japan with HeartWare ventricular assist system.
AB  - We describe the first clinical experiences in Japan with the HeartWare
      ventricular assist device (HVAD: HeartWare Inc., Miami Lakes, FL, USA) in
      patients awaiting heart transplantation. Nine patients (6 males, 3 females; mean
      33.5 +/- 7.8 years; New York Heart Association class III or IV) received the HVAD
      as a bridge to transplantation between 2011 and 2012. Six had dilated
      cardiomyopathy, 2 secondary cardiomyopathy, and 1 dilated phase hypertrophic
      cardiomyopathy. All operations were uneventful, with a mean operation time of 269
      +/- 77 min and cardiopulmonary bypass time of 121 +/- 40 min. One required a
      temporary right ventricular assist device and was weaned on postoperative day 20,
      while another required pump exchange due to foreign tissue in the inflow. Mean
      support duration was 245 +/- 162 days (range: 50-535 days) and mean pump blood
      flow at 1 month postoperatively was 4.8 +/- 0.8 l/min. There was no mortality
      after 30 days, though 1 patient died during support due to cerebral hemorrhage.
      Presently, the others are waiting for heart transplantation without problems,
      except 1 who suffered from an active infection. There was no pump mechanical
      failure in any case. The HeartWare pump enables quick implantation with
      acceptable morbidity and mortality. Our preliminary results indicate that this
      left ventricular assist device is safe for circulatory assistance for heart
      transplant candidates in Japan. 

PMID- 24464395
TI  - Suppressing the expression of a forkhead transcription factor disrupts the chitin
      biosynthesis pathway in Spodoptera exigua.
AB  - Forkhead (Fox) transcription factors display functional diversity and are
      involved in various metabolic and developmental processes. The Spodoptera exigua
      Fox (SeFox) encodes a protein of 353 amino acids with a theoretical molecular
      mass of approximately 38.99 kDa and an isoelectric point of 8.86. qPCR results
      revealed that SeFox was expressed mainly in the brain, fat body, epidermis,
      midgut, Malpighian tubules, and testis. SeFox was expressed, with some changes,
      throughout development in the fat body and whole body. Injection of dsSeFox
      (SeFox dsRNA) into larvae resulted in incidences of albino plus molting deformity
      (4.8%), molting deformity (26.2%), and albino phenotypes (69.1%). dsSeFox
      injection resulted in approximately 50% knockdown of transcript levels at 36 h.
      Compared with control groups, hexokinase (HK) expression was reduced to
      approximately 40% at 48 h postinjection. Chitin synthase A (CHSA) expression was
      reduced to two-thirds at 24 h, but increased at 72 h. Compared with untreated
      control and green fluorescent protein-treated groups, Chitin synthase B (CHSB)
      expression decreased to 33% following dsSeFox injection by 36 h. We infer from
      our results that forkhead transcription factors act in chitin synthesis in S.
      exigua. 

PMID- 24464396
TI  - An automated monitoring of atmospheric mixing height from routine radiosonde
      profiles over South Korea using a web-based data transfer method.
AB  - This study describes an effort to estimate atmospheric mixing height using
      vertical profiles of thermodynamic variables measured operationally at radiosonde
      sites in South Korea. We focus on mixing height at 06UTC (15LST) when vigorous
      daytime convection is expected with clear skies. For this purpose, we developed a
      simple numerical algorithm using a new data transfer tool, known as cURL, to
      determine mixing height and applied it to radiosonde data at Osan and Gwangju for
      2010. Emphasis was placed on automating as much as possible the process of
      determining mixing height. According to the preliminary results, the estimation
      algorithm performed successfully for most cases with clear sky conditions and was
      useful in diagnosing and monitoring daytime mixing heights more effectively on a
      near-real-time basis. With the developed algorithm, it is possible to estimate
      mixing heights from radiosonde data within a few hours of the development of the
      convective boundary layer. Application to radiosonde sites in other countries is
      straightforward and continued modifications of the algorithm are anticipated in
      the near future. 

PMID- 24464397
TI  - Occurrence of perfluorinated compounds in the aquatic environment as found in
      science park effluent, river water, rainwater, sediments, and biotissues.
AB  - The current article maps perfluoroalkyl acids (PFAAs) contamination in the
      largest Science Park of Taiwan. The occurrence of ten target PFAAs in the
      effluent of an industrial wastewater treatment plant (IWWTP), its receiving
      rivers, rainwater, sediment, and the muscles and livers of fish was investigated.
      All target PFAAs were found in effluent of IWWTP, in which perfluorooctane
      sulfonate (PFOS) (6,930 ng/L), perfluorohexyl sulfonate (PFHxS) (2,662 ng/L) and
      perfluorooctanoic acid (PFOA) (3,298 ng/L) were the major constituents.
      Concentrations of PFBS and PFOS in the IWWTP downstream areas have exceeded safe
      concentration levels of avian and aquatic life, indicating a potential risk to
      wildlife in those areas. In sediment samples, predominant contaminants were PFOS
      (1.5-78 ng/g), PFOA (0.5-5.6 ng/g), and perfluorododecanoic acid (PFDoA) (nd-5.4
      ng/g). In biological tissue samples, concentrations as high as 28,933 ng/g of
      PFOS were detected in tilapia and catfish liver samples. A positive correlation
      for log (C sediment/C water) and log (C tissue/C water) was found. The
      concentration and proportion (percentage of all PFAAs) of PFOS found in biotissue
      samples from the Keya River (which receives industrial wastewater) were found to
      be much greater (200 times) than those of samples from the Keelung River (which
      receives mainly domestic wastewater). These findings suggest that the receiving
      aquatic environments and, in turn, the human food chain can be significantly
      influenced by industrial discharges.

PMID- 24464398
TI  - Metal release from serpentine soils in Sri Lanka.
AB  - Ultramafic rocks and their related soils (i.e., serpentine soils) are non
      anthropogenic sources of metal contamination. Elevated concentrations of metals
      released from these soils into the surrounding areas and groundwater have
      ecological-, agricultural-, and human health-related consequences. Here we report
      the geochemistry of four different serpentine soil localities in Sri Lanka by
      coupling interpretations garnered from physicochemical properties and chemical
      extractions. Both Ni and Mn demonstrate appreciable release in water from the
      Ussangoda soils compared to the other three localities, with Ni and Mn metal
      release increasing with increasing ionic strengths at all sites. Sequential
      extraction experiments, utilized to identify "elemental pools," indicate that Mn
      is mainly associated with oxides/(oxy)hydroxides, whereas Ni and Cr are bound in
      silicates and spinels. Nickel was the most bioavailable metal compared to Mn and
      Cr in all four soils, with the highest value observed in the Ussangoda soil at
      168 +/- 6.40 mg kg(-1) via the 0.01-M CaCl2 extraction. Although Mn is dominantly
      bound in oxides/(oxy)hydroxides, Mn is widely dispersed with concentrations
      reaching as high as 391 mg kg(-1) (Yudhaganawa) in the organic fraction and 49 mg
      kg(-1) (Ussangoda) in the exchangeable fraction. Despite Cr being primarily
      retained in the residual fraction, the second largest pool of Cr was in the
      organic matter fraction (693 mg kg(-1) in the Yudhaganawa soil). Overall, our
      results support that serpentine soils in Sri Lanka offer a highly labile source
      of metals to the critical zone.

PMID- 24464399
TI  - Relationship between land use classification and grass shrimp Palaemonetes spp.
      population metrics in coastal watersheds.
AB  - Estuaries in the southeastern USA have experienced increased loading of
      contaminants from nonpoint source runoff as well as changes in habitat (e.g.,
      loss of wetlands) due to urbanization. These changes may pose significant risks
      to estuarine fauna, including crustaceans. Several studies have shown
      relationships between land use classification and levels of stress in estuarine
      populations. The grass shrimp of the genus Palaemonetes is one of the dominant
      species found in estuarine tidal creeks, accounting for more than 50 % of all
      macropelagic fauna. Grass shrimp populations were sampled monthly for 3 years at
      six estuarine creeks on Kiawah Island, SC. Creek watersheds were estimated using
      National Aerial Photograph Program color infrared and low-altitude true color
      aerial photography combined with in situ differentially corrected global
      positioning system mapping of engineered features. Land classifications
      delineated included water, marsh, buildings, roads, and lawns. Pairwise
      comparisons for grass shrimp densities among sites showed significant differences
      on an annual and seasonal basis. Significant relationships (p < 0.05) between
      land class variables and grass shrimp density were identified both annually and
      seasonally. These findings suggest an influence of land use on Palaemonetes spp.
      populations.

PMID- 24464400
TI  - Temperature inversion characteristics in relation to synoptic circulation above
      Athens, Greece.
AB  - In this paper, the characteristic properties of inversions formed inside the
      lower boundary layer over Athens, Greece, were studied using 35-year radiosonde
      measurements of temperature, humidity, and atmospheric pressure. The analysis
      revealed that the inversion parameters demonstrate considerable seasonal
      variation. Specifically, inversions associated with weak anticyclonic conditions
      are more frequent during the winter and summer months, while during spring, weak
      lows are more probable to produce inversions. Some theoretically expected
      associations between synoptic circulation patterns and certain inversion
      parameters were also identified. 

PMID- 24464401
TI  - Macrobenthos response to sewage pollution in a tropical inshore area.
AB  - Organic sewage pollution is the major stressor that affects benthic communities
      in the coastal waters. In the present study involving a once-off sampling (July
      August 2003) of a sewage treatment plant (STP) outfall and areas 6 km farther
      into the sea, we tried to estimate the severity of organic pollution on marine
      macrobenthos over a pollution gradient in the inshore waters (station depths, 5
      30 m) off a heavily urbanized tropical city, on the east coast of India.
      Multivariate ordination analyses revealed two different groups of faunal
      assemblages. Group I is associated with sites impacted by the sewage outfall and
      group II with the locations 3-6 km away in the open sea. Polychaetes and
      amphipods were the predominant fauna with significant taxonomic differences
      between the assemblages. Despite the homogeneity in sediment texture, the two
      fold increase in sediment organic matter near the sewage outfall area supported r
      strategists, while group II locations favoured K-strategists. Approximation
      through benthic opportunistic polychaetes amphipods (BOPA) index and information
      on the key taxa responsible for the observed assemblage patterns corroborated
      these findings. Thus, the present findings revealed how organic sewage pollution
      influences benthic diversity in coastal waters by supporting communities of
      opportunistic characteristics. We advocate inclusion of community traits and
      compatible analytical tools (statistical approaches) in studies of similar nature
      so that the observations could be compared and broad remedial measures could be
      evolved.

PMID- 24464402
TI  - Compliance with National Comprehensive Cancer Network guidelines in the use of
      radiation therapy for extremity and superficial trunk soft tissue sarcoma in the
      United States.
AB  - BACKGROUND: We sought to examine adherence to National Comprehensive Cancer
      Network guidelines for use of radiation therapy (RT) in patients with soft tissue
      sarcoma (STS) in the United States. METHODS: The surveillance, epidemiology, and
      end results cancer registry was queried to identify patients undergoing surgery
      for truncal and extremity STS from 2004 to 2009. RESULTS: Of 5,075 patients, 50%
      received RT. Although routine RT is not recommended for Stage I patients, 25%
      still underwent RT. Even though routine RT is recommended for Stage II and III
      tumors, only 60% underwent RT. On multivariate analysis predictors of RT included
      age <50 years (OR 1.57, 95% CI 1.28-1.91), malignant fibrous histiocytoma
      histology (OR 1.47, 95% CI 1.3-1.92), T2 classification (OR 1.88, 95% CI 1.60
      2.20), and G3 (OR 6.27, 95% CI 5.10-7.72). Patients with Stage III STS who
      received RT showed improved disease specific survival at 5 years compared to
      those who did not, 68% versus 46%, P <0.001. CONCLUSIONS: Underuse of RT is seen
      for a significant proportion of patients undergoing treatment for STS in the
      United States. More effort needs to be directed towards compliance with
      appropriate treatment recommendations, perhaps by regionalizing sarcoma care or
      remote multidisciplinary tumor boards.

PMID- 24464403
TI  - Hazardous alcohol use and intimate partner aggression among dating couples: the
      role of impulse control difficulties.
AB  - To date, research identifying moderators of the alcohol-intimate partner
      aggression (IPA) relationship has focused almost exclusively on male-perpetrated
      aggression, without accounting for the dyadic processes of IPA. The current study
      examined hazardous alcohol use and impulse control difficulties as predictors of
      IPA among a sample of 73 heterosexual dating couples. Both actor and partner
      effects of these risk factors on physical and psychological aggression were
      examined. Results indicated that impulse control difficulties were an important
      actor and partner predictor of both physical and psychological aggression.
      Findings supported the multiple threshold model such that the interaction between
      impulse control difficulties and hazardous alcohol use significantly predicted
      physical aggression severity. These results suggest the importance of targeting
      impulse control difficulties and hazardous alcohol use in IPA treatment, as well
      as the advantages of examining risk factors of IPA within a dyadic rather than
      individual framework.

PMID- 24464404
TI  - Competing imperatives? Moral and public health duties of preventing and treating
      infectious disease in prisons.

PMID- 24464405
TI  - Preliminary Evidence for a Nexus between Rumination, Behavioural Avoidance,
      Motive Satisfaction and Depression.
AB  - The present study tested a theoretically derived link between rumination and
      depressive symptoms through behavioural avoidance and reduced motive satisfaction
      as a key aspect of positive reinforcement. Rumination, behavioural avoidance,
      motive satisfaction and levels of depression were assessed via self-report
      measures in a clinical sample of 160 patients with major depressive disorder.
      Path analysis-based mediation analysis was used to estimate the direct and
      indirect effects as proposed by the theoretical model. Operating in serial,
      behavioural avoidance and motive satisfaction partially mediated the association
      between rumination and depressive symptoms, irrespective of gender, medication
      and co-morbid anxiety disorders. This is the first study investigating the
      associations between behavioural avoidance, rumination and depression in a
      clinical sample of depressed patients. The findings are in line with an
      understanding of rumination in depression as also serving an avoidance function.
      KEY PRACTITIONER MESSAGE: Rumination, avoidance, motive satisfaction and levels
      of depressive symptoms were examined in a clinical sample of 160 outpatients with
      major depressive disorder. Path analysis-based mediation analysis revealed that,
      operating in serial, avoidance and motive satisfaction partially mediated the
      link between rumination and levels of depressive symptoms. Findings support an
      understanding of rumination in depression as serving an avoidance function.

PMID- 24464406
TI  - A Swedish hip arthroscopy registry: demographics and development.
AB  - PURPOSE: Hip arthroscopy is a rapidly expanding field in orthopaedics.
      Indications and surgical procedures are increasing. Although several studies
      report favourable clinical outcomes, further scientific evidence is needed for
      every aspect of this area. Accordingly, a registry for hip arthroscopy was
      developed. The purpose of this study is to describe the development of the
      registry and present its baseline data. METHODS: A Scandinavian expert group
      agreed to use a set of functional outcome scores for the evaluation of hip
      arthroscopy patients. They were the international hip outcome tool-12, hip and
      groin outcome score, EQ-5D, hip-specific activity level scale and visual analogue
      scale for overall hip function. These scores were validated and culturally
      adapted to Swedish. A database was created for web-based, self-administered
      questionnaires. Perioperative data were also collected. RESULTS: The process
      leading to the registry is reported. Baseline data from the first 606 patients
      collected during a 14-month period are presented. The preferred surgical
      technique is presented. The mean operation time was 69 (SD 14) minutes. In 333
      procedures, mixed cam and pincer pathology were addressed, compared with 223
      procedures with the treatment of isolated cam pathology. Outpatient surgery was
      performed in all patients. CONCLUSION: The baseline data in this study can be
      used as reference values for future scientific work from this registry. Knowledge
      of the process leading to the development of the registry could be useful to
      other researchers planning similar work.

PMID- 24464407
TI  - Multiple deployments and combat trauma: do homefront stressors increase the risk
      for posttraumatic stress symptoms?
AB  - Multiple deployments are common among military personnel who served in Operation
      Enduring Freedom and Operation Iraqi Freedom and are associated with greater
      posttraumatic stress symptoms (PTSS). Homefront stressors (i.e., family,
      occupational problems) resulting from deployments may increase the risk of PTSS.
      Moreover, with multiple deployments, a new deployment may occur while still
      experiencing homefront stressors from previous tours. This prospective study
      assessed whether homefront stressors from a previous tour increased the risk of
      PTSS after a new deployment. It also examined the effects of homefront stressors
      at postdeployment. Survey data were obtained from U.S. National Guard soldiers
      with previous deployments prior to (Wave 1) and after (Wave 2) a new deployment
      to Iraq (N = 196). Homefront stressors reported at Wave 1 (beta = .154, p = .015)
      and Wave 2 (beta = .214, p = .002) were both significantly predictive of PTSS at
      postdeployment, even after adjusting for warzone stressors, predeployment PTSS,
      and other variables. A pattern of chronic homefront stressors (i.e., homefront
      stressors at pre- and postdeployment) was associated with higher levels of PTSS
      at postdeployment (beta = .220, p = .002). Service members with multiple
      deployments are at greater risk for PTSS if deployed with homefront stressors
      from previous tours and/or face these stressors at postdeployment. 

PMID- 24464409
TI  - Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on
      precursor cell proliferation in the hippocampus.
AB  - The N-methyl-D-aspartate (NMDA) receptor, one of the ionotropic glutamate
      receptor, plays important physiological and pathological roles in learning and
      memory, neuronal development, acute and chronic neurological diseases, and
      neurogenesis. This work examines the contribution of the NR2B NMDA receptor
      subunit to adult neurogenesis/cell proliferation under physiological conditions
      and following an excitotoxic insult. We have previously shown in vitro that a
      discrete NMDA-induced, excitotoxic injury to the hippocampus results in an
      increase in neurogenesis within the dentate gyrus. Here we have characterized
      adult neurogenesis or proliferation, using BrdU, in an in vivo model of
      excitotoxic injury to the CA1 subfield of the hippocampus. We demonstrate a peak
      in neural stem cell proliferation/neurogenesis between 6 and 9 days after the
      excitotoxic insult. Treatment with ifenprodil, an NR2B subunit-specific NMDA
      receptor antagonist, without prior injury induction, also increased the number of
      BrdU-positive cells within the DG and posterior periventricle, indicating that
      ifenprodil itself could modulate the rate of proliferation. Interestingly,
      though, the increased level of cell proliferation did not change significantly
      when ifenprodil was administered following an excitotoxic insult. In conclusion,
      our results suggest and add to the growing evidence that NR2B subunit-containing
      NMDA receptors play a role in neural stem cell proliferation.

PMID- 24464408
TI  - Provider-patient communication about adherence to anti-retroviral regimens
      differs by patient race and ethnicity.
AB  - Disparities in HIV care and outcomes negatively affect Black and Hispanic
      patients. Features of clinical communication may be a factor. This study is based
      on coding transcripts of 404 routine outpatient visits by people with HIV at four
      sites, using a validated system. In models adjusting for site and patient
      characteristics, with provider as a random effect, providers were more "verbally
      dominant" with Black patients than with others. There was more discussion about
      ARV adherence with both Black and Hispanic patients, but no more discussion about
      strategies to improve adherence. Providers made more directive utterances
      discussing ARV treatment with Hispanic patients. Possible interpretations of
      these findings are that providers are less confident in Black and Hispanic
      patients to be adherent; that they place too much confidence in their White, non
      Hispanic patients; or that patients differentially want such discussion. The lack
      of specific problem solving and high provider directiveness suggests areas for
      improvement.

PMID- 24464410
TI  - Giant cell encephalitis and microglial infection with mucosally transmitted
      simian-human immunodeficiency virus SHIVSF162P3N in rhesus macaques.
AB  - Neurocognitive disorders such as dementia and cognitive/motor impairments are
      among the most significant complications associated with human immunodeficiency
      virus (HIV) infection, especially in aging populations, yet the pathogenesis
      remains poorly understood. Activated macrophages and microglia in white matter
      along with the hallmark multinucleated giant cells are prominent features of HIV
      encephalitis (HIVE) and of several simian immunodeficiency virus (SIV) models.
      While infected microglia have been demonstrated in HIVE, this feature is not
      routinely seen in experimental infections in rhesus macaques using SIV or
      chimeric simian/HIV (SHIV) strains, limiting utility in HIV-1 pathogenesis and
      treatment studies. Here, 50 rhesus macaques were inoculated with the CCR5 (R5)
      tropic SHIVSF162P3N virus by one of three routes: intravenously (n = 9),
      intrarectally (n = 17), or intravaginally (n = 24). Forty-three monkeys became
      viremic, 26 developed AIDS, and 7 (7/26, 27 %) developed giant cell SIV
      encephalitis (SIVE). Rapid progressor phenotype was evident in five of seven (71
      %) macaques with SIVE, and expansion to utilize the CXCR4 coreceptor (X4
      coreceptor switch) was observed in four out of seven (57 %). SIVE lesions were
      present in gray and white matter in the cerebrum, cerebellum, thalamus, and brain
      stem of affected animals. Lesions were composed of virally infected CD68(+),
      CD163(+), and HLA-DR(+) macrophages accompanied by white matter damage, necrosis,
      and astroglial and microglial activation. Importantly, microglial infection was
      observed, which makes R5 SHIVSF162P3N infection of macaques an attractive animal
      model not only to study transmission and HIVE pathogenesis but also to conduct
      preclinical evaluation of therapeutic interventions aimed at eradicating HIV-1
      from the central nervous system (CNS).

PMID- 24464412
TI  - Acute hypokalemic quadriparesis: an atypical neurological manifestation of dengue
      virus.

PMID- 24464411
TI  - Gene expression analysis in children with complex seizures due to influenza
      A(H1N1)pdm09 or rotavirus gastroenteritis.
AB  - Viral infections have been implicated as a cause of complex seizures in children.
      The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or
      rotavirus gastroenteritis remain unclear. This study analyzed the gene expression
      profiles in the peripheral whole blood from pediatric patients with complex
      seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene
      expression profiles of ten patients (five with seizures and five without) with
      influenza A(H1N1)pdm09 and six patients (three with seizures and three without)
      with rotavirus gastroenteritis were examined. Gene expression profiles in the
      whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or
      rotavirus gastroenteritis. Transcripts related to the immune response were
      significantly differentially expressed in complex seizures with influenza
      A(H1N1)pdm09, and transcripts related to the stress response were significantly
      differentially expressed in complex seizures with rotavirus gastroenteritis.
      Pathway analysis showed that the mitogen-activated protein kinases in the T cell
      receptor signaling pathway were activated in complex seizures due to influenza
      A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress
      response could contribute to the pathogenic differences of the complex seizures
      due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. 

PMID- 24464413
TI  - Dramatic improvement of parkinsonian symptoms after gluten-free diet introduction
      in a patient with silent celiac disease.

PMID- 24464414
TI  - Performance nutrition guidelines for international rugby sevens tournaments.
AB  - Rugby sevens is an abbreviated version of rugby union, played by teams of seven
      players over 7-min halves. International competitions are usually played in a
      tournament format. While shorter in duration, the movement demands of rugby
      sevens per min of match time are greater than rugby union, resulting in an
      accentuated load on players. This load can be repeated up to six times over a
      typical 2- or 3-day competition period. The potential cumulative effect of
      inadequate carbohydrate, protein and/or fluid intake over the course of a
      tournament is the greatest nutrition-related concern for players. Nutritional
      strategies before and during competition are suggested to replenish substrate
      stores, maintain fluid balance and promote recovery between matches. The use of
      ergogenic aids known to enhance intermittent, high-intensity activity and/or the
      execution of motor skills may be advantageous to rugby sevens performance and is
      discussed. This review provides a best-practice model of nutritional support for
      international rugby sevens competition based on our current understanding of the
      sport combined with pragmatic guidelines and considerations for the practitioner.

PMID- 24464415
TI  - Physician, heal thyself: a qualitative study of physician health behaviors.
AB  - OBJECTIVE: The authors explore how physicians perceive their own health and
      barriers to healthcare, as well as what might motivate their behavior. METHODS:
      This qualitative study uses semi-structured interviews of a purposive sampling of
      physicians, both staff and housestaff, from Walter Reed Army Medical Center and
      the Medical College of Wisconsin. Transcripts of interviews that probed attitudes
      and behaviors towards self-care were coded independently by two reviewers using
      grounded theory qualitative methods. RESULTS: The authors conducted 28 interviews
      until no new themes emerged. Common barriers to healthcare included inadequate
      time, fear of consequences, and concern about confidentiality, particularly for
      stigmatizing diseases identified as mental health problems, chronic pain,
      substance abuse, and sexual dysfunction. Common behaviors included neglecting
      one's health, minimizing symptoms, self-diagnosing, and a strong desire not to
      burden colleagues. Participants were split into those who felt it was fine to
      self-medicate and others who avoided it. Participants proposed solutions for
      identified problems, including building time into schedules for self-care,
      monitoring electronic medical record access to make providers accountable,
      obtaining care at other institutions, and working to change the culture around
      healthcare for physicians. CONCLUSIONS: All participants in this study perceived
      significant unresolved issues pertaining to self-care. Physicians commonly
      neglect their own care and experience barriers to care, some self-generated and
      some systems based. The results and suggested interventions provide fodder for
      future research.

PMID- 24464416
TI  - Impact of the psychiatry clerkship on medical student attitudes towards
      psychiatry and to psychiatry as a career.
AB  - OBJECTIVE: The psychiatry clerkship forms part of the core curriculum of medical
      schools worldwide and provides psychiatric educators with an ideal opportunity to
      positively influence students. The aim of this paper is to systematically review
      literature on the impact of the psychiatry clerkship to determine the effect on
      attitudes towards psychiatry and to psychiatry as a career. METHOD: A systematic
      review was undertaken. The following key search words were used to search a
      number of electronic databases: medical student/s, attitude/s, psychiatry and
      clerkship. Studies published in the English language from 1990 to the present
      were included. Studies were included if they were based on a pre-/post-design,
      i.e. the same students must have participated in the study both before and after
      the clerkship. RESULTS: Twenty-six studies from 19 countries were identified for
      the review. Sixteen studies reported an overall improvement in attitudes towards
      psychiatry post-clerkship, and ten found no change in attitudes. In terms of
      career choice, nine studies reported an increase in the number of students
      interested in psychiatry as a career post-clerkship, nine found no impact on
      career choice and, in eight studies, it was not assessed. A number of positive
      and negative factors regarding the clerkship were identified. CONCLUSION:
      Overall, the psychiatry clerkship has a positive impact on students' attitudes
      towards psychiatry, but does not improve interest in psychiatry as a career
      option. For those students particularly interested in psychiatry, the challenge
      is to maintain their enthusiasm post-clerkship. Charismatic teachers, mentorship
      and stigma reduction may be effective strategies. Future research needs to more
      clearly identify specific components of the clerkship that are viewed favorably
      by students.

PMID- 24464417
TI  - In reply to "Patient satisfaction questionnaires in trainee evaluations".

PMID- 24464420
TI  - Abstracts of the 19th Congress of the Spanish Society for Surgical Research,
      Madrid, November 2013.

PMID- 24464418
TI  - Aging genomes: a necessary evil in the logic of life.
AB  - Genomes are inherently unstable because of the need for DNA sequence variation as
      a substrate for evolution through natural selection. However, most multicellular
      organisms have postmitotic tissues, with limited opportunity for selective
      removal of cells harboring persistent damage and deleterious mutations, which can
      therefore contribute to functional decline, disease, and death. Key in this
      process is the role of genome maintenance, the network of protein products that
      repair DNA damage and signal DNA damage response pathways. Genome maintenance is
      beneficial early in life by swiftly eliminating DNA damage or damaged cells,
      facilitating rapid cell proliferation. However, at later ages accumulation of
      unrepaired damage and mutations, as well as ongoing cell depletion, promotes
      cancer, atrophy, and other deleterious effects associated with aging. As such,
      genome maintenance and its phenotypic sequelae provide yet another example of
      antagonistic pleiotropy in aging and longevity. 

PMID- 24464421
TI  - No radiographic difference between patient-specific guiding and conventional
      Oxford UKA surgery.
AB  - PURPOSE: Implant position is an important factor in unicompartmental knee
      arthroplasty (UKA) surgery. Results on conventional UKA alignment are commonly
      described in literature. Patient-specific guiding (PSG) is a new technique for
      positioning the Oxford UKA. Our hypothesis is that PSG improves component
      position without affecting the HKA angle. METHODS: This prospective study
      compares the results of our first thirty cases of cementless Oxford UKA using PSG
      with thirty cases using conventional outlining. Baseline characteristics for both
      groups were identical. Details on handling of the guide, estimated blood loss and
      operation time were recorded. Postoperative screened radiographs and standing
      long-leg radiographs of both groups were compared. RESULTS: Median AP position of
      the femoral component was 3 degrees varus (-5 to 9) using PSG versus 2 degrees
      varus (-10 to 8) for the conventional group. For the femoral flexion, this was 9
      degrees flexion (0-16) using PSG versus 12 degrees flexion (0-20). The tibial
      median AP position was 1 degree varus (-3 to 7) using PSG versus 2 degrees varus
      (-5 to 10). The median tibial posterior slope was 5 degrees (1-10) using PSG
      versus 5 degrees (0-12). All guides aligned well. No conversion to conventional
      outlining was performed, and no significant changes had to be made to the
      original approved plan. Operation time, estimated blood loss and postoperative
      haemoglobin drop were not significantly different between both groups.
      DISCUSSION: Implant position was not different between both groups, even in the
      early phase of the learning curve. Perioperative results were not different
      between both groups. LEVEL OF EVIDENCE: III.

PMID- 24464422
TI  - Vaccine therapies for chronic hepatitis B: can we go further?
AB  - Chronic hepatitis B is a major health burden worldwide. In addition to the recent
      progress in antiviral treatment, therapeutic vaccination is a promising new
      strategy for the control of chronic hepatitis B. On the basis of the major
      specific and non-specific immune dysregulations and defects in chronic hepatitis
      B patients, this paper presents the peptide and protein-based, DNA-based, cell
      based, and antigen-antibody-based therapeutic vaccines, which have undergone
      clinical trials. The advantages, disadvantages, and future perspectives for these
      therapeutic vaccines are discussed. 

PMID- 24464423
TI  - The cortical and cerebellar representation of the lumbar spine.
AB  - Eight decades after Penfield's discovery of the homunculus only sparse evidence
      exists on the cortical representation of the lumbar spine. The aim of our
      investigation was the description of the lumbar spine's cortical representation
      in healthy subjects during the application of measured manual pressure. Twenty
      participants in the prone position were investigated during functional magnetic
      resonance imaging (fMRI). An experienced manual therapist applied non-painful,
      posterior-to-anterior (PA) pressure on three lumbar spinous processes (L1, L3,
      and L5). The pressure (30 N) was monitored and controlled by sensors. The
      randomized stimulation protocol consisted of 68 pressure stimuli of 5 s duration.
      Blood oxygenation level dependent (BOLD) responses were analyzed in relation to
      the lumbar stimulations. The results demonstrate that controlled PA pressure on
      the lumbar spine induced significant activation patterns. The major new finding
      was a strong and consistent activation bilaterally in the somatosensory cortices
      (S1 and S2). In addition, bilateral activation was located medially in the
      anterior cerebellum. The activation pattern also included other cortical areas
      probably related to anticipatory postural adjustments. These revealed stable
      somatosensory maps of the lumbar spine in healthy subjects can subsequently be
      used as a baseline to investigate cortical and subcortical reorganization in low
      back pain patients.

PMID- 24464424
TI  - Improved B0 -distortion correction in diffusion MRI using interlaced q-space
      sampling and constrained reconstruction.
AB  - PURPOSE: To enable high-quality correction of susceptibility-induced geometric
      distortion artifacts in diffusion magnetic resonance imaging (MRI) images without
      increasing scan time. THEORY AND METHODS: A new method for distortion correction
      is proposed based on subsampling a generalized version of the state-of-the-art
      reversed-gradient distortion correction method. Rather than acquire each q-space
      sample multiple times with different distortions (as in the conventional reversed
      gradient method), we sample each q-space point once with an interlaced sampling
      scheme that measures different distortions at different q-space locations.
      Distortion correction is achieved using a novel constrained reconstruction
      formulation that leverages the smoothness of diffusion data in q-space. RESULTS:
      The effectiveness of the proposed method is demonstrated with simulated and in
      vivo diffusion MRI data. The proposed method is substantially faster than the
      reversed-gradient method, and can also provide smaller intensity errors in the
      corrected images and smaller errors in derived quantitative diffusion parameters.
      CONCLUSION: The proposed method enables state-of-the-art distortion correction
      performance without increasing data acquisition time.

PMID- 24464425
TI  - Genetic analysis of human parainfluenza viruses circulating in Korea, 2006.
AB  - Human parainfluenza viruses (HPIV) are important causes of respiratory tract
      infections in young children. To characterize the molecular epidemiology of an
      HPIV outbreak occurring in Korea during 2006, genetic analysis of 269 cell
      culture isolates from HPIV-infected children, was conducted using nested reverse
      transcription-PCR (RT-PCR). HPIV-1 was detected in 70.3% of tested samples
      (189/269). The detection rate of HPIV-2 and HPIV-3 was 1.5% (4/269) and 9.3%
      (25/269), respectively. Mixed HPIV-1, -2 and -3 infections were detected in 19.0%
      (51/269): HPIV-1 and HPIV-2 in 15, HPIV-1 and HPIV-3 in 26, HPIV-2 and HPIV-3 in
      6, and HPIV-1, -2 and -3 in 4. Of these positive samples for three different
      types HIPV-1, -2, and -3, two each representative strains were selected, the full
      length of hemagglutinin-neuraminidase (HN) gene for HPIV was amplified by RT-PCR,
      and sequenced. Multiple alignment analysis, based on reference sequence of HPIV
      1, -2, and -3 strains available in GenBank, showed that the identity of
      nucleotide and deduced amino acid sequences was 92.4-97.6% and 92.7-97.9%,
      respectively, for HPIV-1, 88.5-99.8% and 88.6-100% for HPIV-2, and 96.3-99.5% and
      95.0-99.3% for HPIV-3, respectively. Phylogenetic analysis showed that HPIV-1, 
      2, and -3 strains identified in this study were closely related among the strains
      in the same type with no significant genetic variability. These results show that
      HPIV of multiple imported sources was circulating in Korea.

PMID- 24464426
TI  - Introduction to the 12th International Workshop on Developmental Nephrology.

PMID- 24464427
TI  - Use of strategies to improve retention in primary care randomised trials: a
      qualitative study with in-depth interviews.
AB  - OBJECTIVE: To explore the strategies used to improve retention in primary care
      randomised trials. DESIGN: Qualitative in-depth interviews and thematic analysis.
      PARTICIPANTS: 29 UK primary care chief and principal investigators, trial
      managers and research nurses. METHODS: In-depth face-to-face interviews. RESULTS:
      Primary care researchers use incentive and communication strategies to improve
      retention in trials, but were unsure of their effect. Small monetary incentives
      were used to increase response to postal questionnaires. Non-monetary incentives
      were used although there was scepticism about the impact of these on retention.
      Nurses routinely used telephone communication to encourage participants to return
      for trial follow-up. Trial managers used first class post, shorter questionnaires
      and improved questionnaire designs with the aim of improving questionnaire
      response. Interviewees thought an open trial design could lead to biased results
      and were negative about using behavioural strategies to improve retention. There
      was consensus among the interviewees that effective communication and rapport
      with participants, participant altruism, respect for participant's time,
      flexibility of trial personnel and appointment schedules and trial information
      improve retention. Interviewees noted particular challenges with retention in
      mental health trials and those involving teenagers. CONCLUSIONS: The findings of
      this qualitative study have allowed us to reflect on research practice around
      retention and highlight a gap between such practice and current evidence.
      Interviewees describe acting from experience without evidence from the
      literature, which supports the use of small monetary incentives to improve the
      questionnaire response. No such evidence exists for non-monetary incentives or
      first class post, use of which may need reconsideration. An exploration of
      barriers and facilitators to retention in other research contexts may be
      justified.

PMID- 24464428
TI  - Racial/ethnic identity and subjective physical and mental health of Latino
      Americans: an asset within?
AB  - Social Identity Theory indicates that ethnic identity could benefit minority
      members in a society because of its promotion of a sense of belonging, or of its
      buffering of the damage of discrimination. Despite growing investigation about
      Latinos' overall health, few studies have simultaneously examined the influence
      of multiple cultural strength factors, especially racial/ethnic identity, social
      support, and religious attendance, on these outcomes. Using the National Latino
      and Asian American Study, we examine the potential predictive value of these
      cultural strength factors on Latinos' Self-Rated Mental and Physical Health (SRMH
      and SRPH). Two separate two-step regression models revealed significant positive
      effects of racial/ethnic identity on both mental and physical health of Latinos,
      above and beyond the effect of known demographic and acculturation factors, such
      as discrimination. Religious attendance had a positive effect on SRMH but not on
      SRPH. The deteriorating roles of discrimination, in mental health only, and that
      of Length in the US in both outcomes, however, was primarily not altered by entry
      of these cultural strength factors. The independent direct effect of
      racial/ethnic identity among Latinos nationwide may suggest that this cultural
      strength is an internalized protective asset. Longitudinal data is needed to
      explore its underlying mechanism and long-term impact. 

PMID- 24464429
TI  - Impact of combat deployment on psychological and relationship health: a
      longitudinal study.
AB  - Although previous research has indicated an elevated prevalence of posttraumatic
      stress disorder (PTSD) and other mental health problems among veterans of
      Operations Iraqi Freedom and Enduring Freedom following deployment, most of this
      research has been cross-sectional and has focused on a limited range of military
      groups and outcome criteria. This investigation was a longitudinal study of U.S.
      Air Force security forces assigned to a year-long high-threat ground mission in
      Iraq to determine the degree to which airmen's emotional and behavioral health
      and committed relationships were adversely impacted by an extended deployment to
      a warzone. Participants were a cohort of 164 security forces airmen tasked to a
      365-day deployment to train Iraqi police. Airmen completed study measures both
      prior to and 6-9 months following deployment. Rates of deterioration in
      individual and interpersonal adjustment were both significant and medium to large
      in magnitude of effect, d = 0.43 to 0.90. Results suggest that the negative
      effects of deployment are related to levels of traumatic experiences and do not
      spontaneously remit within the first 6-9 months following return from deployment
      particularly among those service members having relatively lower levels of social
      support. 

PMID- 24464430
TI  - Bradykinin regulates the expression of claudin-5 in brain microvascular
      endothelial cells via calcium-induced calcium release.
AB  - To investigate the mechanism underlying the regulation of claudin-5, a tight
      junction protein that participates primarily in the constitution of the blood
      brain barrier by bradykinin (BK), we established a primary culture of rat brain
      microvascular endothelial cells (BMECs). BMECs were treated with 10(-5) M BK, and
      changes in the intracellular Ca(2+) levels were measured by using the sensitive
      fluorescent dye fluo-3; the expression and distribution of claudin-5 were
      investigated by immunocytochemistry and Western blot analyses. We did not detect
      any expression of bradykinin B2 receptors in the BMECs or freshly isolated rat
      brain microvessels. We found that 10(-5) M BK triggered Ca(2+) transients in
      BMECs, and further investigations revealed that inositol 1,4,5-trisphosphate
      receptors (IP3 Rs) and ryanodine receptors (RyRs) on the endoplasmic reticulum
      (ER) were responsible for the Ca(2+) fluctuation. Consequently, these
      intracellular Ca(2+) changes that occur in response to BK application were
      identified as Ca(2+) -induced Ca(2+) release (CICR). Immunocytochemistry and
      Western blot results demonstrated that 10(-5) M BK could cause the
      internalization and a decrease in the expression of claudin-5; agonists of IP3 Rs
      and RyRs, such as IP3 and caffeine, enhanced the BK-induced downregulation of
      claudin-5, whereas antagonists of IP3 Rs and RyRs, such as 2-APB and ryanodine,
      abrogated BK's effect on claudin-5. In conclusion, the BK-induced CICR in primary
      culture BMECs might be the mechanism by which BK modulates claudin-5.

PMID- 24464432
TI  - Development of a cell-based, high-throughput screening assay for ATM kinase
      inhibitors.
AB  - The ATM (ataxia-telangiectasia, mutated) protein kinase is a major regulator of
      cellular responses to DNA double-strand breaks (DSBs), DNA lesions that can be
      caused by ionizing irradiation (IR), oxidative damage, or exposure to certain
      chemical agents. In response to DSBs, the ATM kinase is activated and
      subsequently phosphorylates numerous downstream substrates, including p53, Chk2,
      BRCA1, and KAP1, which affect processes such as cell cycle progression and DNA
      repair. Numerous studies have demonstrated that loss of ATM function results in
      enhanced sensitivity to ionizing irradiation in clinically relevant dose ranges,
      suggesting that ATM kinase is an attractive therapeutic target for enhancing
      tumor cell kill with radiotherapy. Previously identified small-molecule ATM
      kinase inhibitors, such as CP466722 and Ku55933, were identified using in vitro
      kinase assays carried out with recombinant ATM kinase isolated from mammalian
      cells. Since it has not been feasible to express full-length recombinant ATM in
      bacterial or baculovirus systems, a robust in vitro screening tool has been
      lacking. We have developed a cell-based assay that is robust, straightforward,
      and sensitive. Using this high-throughput assay, we screened more than 7000
      compounds and discovered additional small molecules that inhibit the ATM kinase
      and further validated these hits by secondary assays. 

PMID- 24464431
TI  - Global Human-Kinase Screening Identifies Therapeutic Host Targets against
      Influenza.
AB  - During viral infection of human cells, host kinases mediate signaling activities
      that are used by all viruses for replication; therefore, targeting of host
      kinases is of broad therapeutic interest. Here, host kinases were globally
      screened during human influenza virus (H1N1) infection to determine the time
      dependent effects of virus infection and replication on kinase function.
      Desthiobiotin-labeled analogs of adenosine triphosphate and adenosine diphosphate
      were used to probe and covalently label host kinases in infected cell lysates,
      and probe affinity was determined. Using infected human A549 cells, we screened
      for time-dependent signal changes and identified host kinases whose probe
      affinities differed significantly when compared to uninfected cells. Our screen
      identified 10 novel host kinases that have not been previously shown to be
      involved with influenza virus replication, and we validated the functional
      importance of these novel kinases during infection using targeted small
      interfering RNAs (siRNAs). The effects of kinase-targeted siRNA knockdowns on
      replicating virus levels were measured by quantitative reverse-transcription PCR
      and cytoprotection assays. We identified several novel host kinases that, when
      knocked down, enhanced or reduced the viral load in cell culture. This
      preliminary work represents the first screen of the changing host kinome in
      influenza virus-infected human cells. 

PMID- 24464433
TI  - Connecting Small Molecules with Similar Assay Performance Profiles Leads to New
      Biological Hypotheses.
AB  - High-throughput screening allows rapid identification of new candidate compounds
      for biological probe or drug development. Here, we describe a principled method
      to generate "assay performance profiles" for individual compounds that can serve
      as a basis for similarity searches and cluster analyses. Our method overcomes
      three challenges associated with generating robust assay performance profiles:
      (1) we transform data, allowing us to build profiles from assays having diverse
      dynamic ranges and variability; (2) we apply appropriate mathematical principles
      to handle missing data; and (3) we mitigate the fact that loss-of-signal assay
      measurements may not distinguish between multiple mechanisms that can lead to
      certain phenotypes (e.g., cell death). Our method connected compounds with
      similar mechanisms of action, enabling prediction of new targets and mechanisms
      both for known bioactives and for compounds emerging from new screens.
      Furthermore, we used Bayesian modeling of promiscuous compounds to distinguish
      between broadly bioactive and narrowly bioactive compound communities. Several
      examples illustrate the utility of our method to support mechanism-of-action
      studies in probe development and target identification projects. 

PMID- 24464434
TI  - Roles of PKC Isoforms in PMA-Induced Modulation of the hERG Channel (Kv11.1).
AB  - Protein kinases C (PKC) modulate the activity of the Kv11.1 ion channel current
      (hERG). However, the differential effects of specific PKC subtypes on the
      biophysics of the channel are unknown. The pharmaceutical tools to selectively
      modulate PKC subtypes are not membrane permeable and must be added directly to
      the intracellular solution in electrophysiology studies. Here, the PatchXpress
      electrophysiology robot was used to voltage clamp up to 16 cells simultaneously
      yet asynchronously across individual Sealchip chambers. The precision afforded by
      repeats of automation procedures minimized the experimental errors typical of
      these assays. Eight well-known PKC selective peptidomimmetics and general
      synthetic modulators were used to modulate the protein-protein interactions
      between hERG and the major PKC subtypes. We identified a specific role for the
      PKCepsilon inhibitory peptidomimmetics in decreasing PKC-induced hERG tau
      activation (80%) and half-maximum activation voltage (90%) at steady state; a
      specific PKCepsilon activator exhibited the opposite effect. Disruption of
      PKCbeta, PKCalpha, and PKCeta interactions also showed significant effects albeit
      of lower magnitudes. The effect of PKCdelta inhibitor was only marginal. A
      significant correlation was observed between the shifts in tau activation and
      half-maximum voltage at steady state (R(2)= 0.85). Peak current amplitudes and
      time constant of deactivation remained unaffected in all conditions. 

PMID- 24464435
TI  - Production of the alpha and beta Subunits of Spirulina Allophycocyanin and C
      Phycocyanin in Escherichia coli : A Comparative Study of Their Antioxidant
      Activities.
AB  - Allophycocyanin and c-phycocyanin have been reported to be potent antioxidants.
      In this work, the genes encoding the apo-proteins of allophycocyanin alpha
      (ApcA), allophycocyanin beta (ApcB), c-phycocyanin alpha (CpcA), and c
      phycocyanin beta (CpcB) from Spirulina platensis were cloned, and the recombinant
      proteins were produced in Escherichia coli to study their antioxidant effects.
      All four recombinant phycocyanins could be produced in the soluble form and
      purified to more than 97% purity. The results of radical scavenging assays showed
      that the Trolox equivalent values for peroxyl radical scavenging by the ApcA,
      ApcB, CpcA, and CpcB proteins were 1.81 +/- 0.2 uM, 1.98 +/- 0.22 uM, 0.95 +/-
      0.15 uM, and 1.49 +/- 0.15 uM, respectively. The IC50 values for hydroxyl radical
      scavenging of ApcA, ApcB, CpcA, CpcB, and Trolox were 269 +/- 9 ug/mL, 190 +/- 5
      ug/mL, 129 +/- 8 ug/mL, 108 +/- 4 ug/mL, and 195 +/- 12 ug/mL, respectively.
      These results indicated that allophycocyanin exhibited higher activity than c
      phycocyanin in scavenging peroxyl radicals, whereas c-phycocyanin exhibited
      higher activity than allophycocyanin in scavenging hydroxyl radicals. All of the
      apo-phycocyanin subunits possessed strong antioxidant activities and can be
      further developed and applied to the food and drug industries. However, the
      selection of the most useful antioxidant should depend on the type of targeted
      free radical to obtain the highest efficiency.

PMID- 24464436
TI  - Alveolar haemorrhage in eosinophilic granulomatosis and polyangiitis (Churg
      Strauss).
AB  - We describe two patients of alveolar haemorrhage in patients with eosinophilic
      granulomatosis with polyangiitis (eGPA). This report adds to the evidence that
      pulmonary haemorrhage is a rare but severe manifestation of eGPA. It may not be
      associated with positive ANCA antibodies and requires aggressive treatment. 

PMID- 24464437
TI  - Short-course treatment of latent tuberculosis infection in patients with
      rheumatic conditions proposed for anti-TNF therapy.
AB  - Tuberculosis reactivation is a serious threat in patients treated with anti
      tumour necrosis factor therapy. A 6-month regimen with isoniazid is considered as
      the standard of care, but patient adherence is a major shortcoming. We carried
      out an open-label, single-arm intervention study to assess the efficacy, the
      completion rate and the tolerability of a 3-month regimen with isoniazid plus
      rifampin. Seventy-eight patients with rheumatic conditions proposed for anti
      tumour necrosis factor (TNF) therapy and at risk of tuberculosis reactivation
      were offered to participate in the study. Nine patients were excluded due to
      deficit of glucose-6-phosphate dehydrogenase (n = 1), salicylate hypersensitivity
      (n = 1), declining to participate (n = 5) or preferring a 6-month isoniazid
      regimen (n = 6). Sixty-nine patients were treated with a 3-month regimen with
      isoniazid and rifampin. No cases of tuberculosis were observed after a mean
      follow-up of 90 months (range from 66 to 121 months). Sixty (87 %) patients
      completed the therapy. Nine (13 %) patients discontinued the therapy due to
      rifampin hypersensitivity (n = 1), symptomatic grade 3-4 hepatotoxicity (n = 2),
      abdominal discomfort (n = 2), pruritus (n = 1), arthritis (n = 1) and personal
      concerns (n = 2). A short course treatment with isoniazid and rifampin provided
      efficacy, good tolerability and good completion rate in patients with rheumatic
      conditions proposed for anti-TNF therapy. 

PMID- 24464438
TI  - Person-organization fit and organizational identification as predictors of
      positive and negative work-home interactions.
AB  - OBJECTIVES: The aim of the presented research was to explore the links between
      complementary and supplementary dimensions of Person-Organization fit (P-O fit),
      organizational identification (OI) and negative (WHI(-)) versus positive (WHI(+))
      work-home interactions. It was assumed that both complementary and supplementary
      P-O fit and OI were positively related to WHI(+) and negatively to WHI(-).
      MATERIALS AND METHODS: The study was conducted on a large sample of Polish blue
      and white collar workers. The subjects were interviewed by means of
      questionnaires measuring: supplementary and complementary dimensions of P-O fit,
      OI and WHI. General work ability and demographic variables were also controlled
      in the study, and statistical analysis of ANOVA, pairwise comparison as well as
      regression were performed. RESULTS: P-O fit and OI differentiated the subjects in
      terms of WHI. For women supplementary fit was a significant predictor of WHI(-)
      and explained 12% of its variance, for men it was complementary fit with the
      number of working days per week and the level of education, which explained 22%
      of variance. Supplementary fit and OI explained 16% of WHI(+) variance in women;
      OI, tenure at the main place of employment and the level of education explained
      8% of WHI(+) variance in men. CONCLUSIONS: It has been proven that not only are
      the effects of P-O fit and OI limited to the work environment but they also
      permeate boundaries between work and home and influence private life - good level
      of P-O fit and good OI play facilitating role in the positive spillover between
      work and home. Gender differences in the significance and predictive values of P
      O fit and OI for WHI were also found. The innovative aspect of the work is the
      inclusion of P-O fit and OI in the range of significant predictors of work-home
      interaction. The results can serve as rationale for employers that improvement of
      P-O fit and employees' organizational identification should be included in work
      life balance programs.

PMID- 24464439
TI  - Towards estimating the burden of disease attributable to second-hand smoke
      exposure in Polish children.
AB  - OBJECTIVES: To estimate the burden of disease attributable to second-hand smoke
      (SHS) exposure in Polish children in terms of the number of deaths and disability
      adjusted life years (DALYs) due to lower respiratory infections (LRI), otitis
      media (OM), asthma, low birth weight (LBW) and sudden infant death syndrome
      (SIDS). MATERIALS AND METHODS: Estimates of SHS exposure in children and in
      pregnant women as well as information concerning maternal smoking were derived
      from a national survey, the Global Youth Tobacco Survey, and the Global Adult
      Tobacco Survey in Poland. Mortality data (LRI, OM, asthma, and SIDS), the number
      of cases (LBW), and population data were obtained from national statistics (year
      2010), and DALYs came from the WHO (year 2004). The burden of disease due to SHS
      was calculated by multiplying the total burden of a specific health outcome
      (deaths or DALYs) by a population attributable fraction. RESULTS: Using two
      estimates of SHS exposure in children: 48% and 60%, at least 12 and 14 deaths
      from LRI in children aged up to 2 years were attributed to SHS, for the two
      exposure scenarios, respectively. The highest burden of DALYs was for asthma in
      children aged up to 15 years: 2412, and 2970 DALYs, for the two exposure
      scenarios, respectively. For LRI, 419 and 500 DALYs, and for OM, 61 and 77 DALYs
      were attributed to SHS, for the two exposure scenarios, respectively. Between 13%
      and 27% of SIDS cases and between 3% and 16% of the cases of LBW at term were
      attributed to SHS exposure. CONCLUSIONS: This study provides a conservative
      estimate of the public health impact of SHS exposure on Polish children. Lack of
      comprehensive, up to date health data concerning children, as well as lack of
      measures that would best reflect actual SHS exposure are major limitations of the
      study, likely to underestimate the burden of disease.

PMID- 24464440
TI  - Health-oriented physical activity in prevention of musculoskeletal disorders
      among young Polish musicians.
AB  - OBJECTIVES: Musicians represent a very specific professional group, which due to
      some occupational hazards is exposed to different health problems known as
      playing-related musculoskeletal disorders (PRMDs). The aim of this study was to
      assess correlations between the level of physical activity, and the occurrence of
      musculoskeletal pain among young instrumentalists. MATERIALS AND METHODS: Total
      of 225 Polish musical school students were investigated. To assess the study
      participants' physical activity level, the moderate to vigorous physical activity
      (MVPA) index was used. To assess pain complaints on the side of the
      musculoskeletal system, Nordic Musculoskeletal Questionnaire (NMQ) was applied.
      The NMQ questionnaire was complemented by adding a visual-analog scale (VAS),
      which also allowed to assess pain intensity on a numerical scale 1-10. RESULTS:
      The pain localized in neck, shoulders, upper and lower back was reported
      significantly more often by the participants who did not meet standard criteria
      for the recommended or minimal physical activity level. CONCLUSION: Performing
      the recommended health-oriented physical activity may reduce the prevalence of
      musculoskeletal pain in young musicians.

PMID- 24464441
TI  - Clinical arterial infusion of calcium gluconate: the preferred method for
      treating hydrofluoric acid burns of distal human limbs.
AB  - OBJECTIVE: This study was designed to evaluate the efficiency and safety of
      arterial infusions of calcium gluconate to treat hydrofluoric (HF) acid burns of
      the distal human limbs. MATERIALS AND METHODS: Eligible patients with HF burn
      limbs, collected from January 2008 to October 2011, were given the arterial
      infusion of calcium gluconate into the injured limbs. The measures of pain were
      conducted before the infusion, immediately after the infusion, 4 h after the
      infusion, and 2 days after the infusion by the visual analogy score (VAS). If the
      VAS score was higher than 4.0 at the time point 4 h after the first infusion, the
      infusion was repeated. The time of wound healing, and the number and ratio of the
      cases receiving the surgical operation were also evaluated. RESULTS: A total of
      118 patients, male (107 cases) and female (11 cases), were collected, including
      64 cases of outpatients and 54 cases of inpatients. The age of the subjects
      ranged from 16 to 60 years, with the mean age of 37.6. The burn sites were
      located in the lateral limbs (28 cases) and in the unilateral limbs (90 cases).
      For 107 cases, the pain scores decreased quickly after the first infusion. The
      other 11 cases, with the VAS score higher than 4.0 at the time point 4 h after
      the first infusion, received the second infusion. The average time of wound
      healing and the ratio of the cases receiving the surgical operation were closely
      related to the interval from the injury to the reception of infusion.
      CONCLUSIONS: Arterial infusion of calcium gluconate, effectively relieving the
      pain, blocking wound progressive deepening, and causing no adverse effects, could
      be the preferential method to treat hydrofluoric acid burns of the distal human
      limbs.

PMID- 24464442
TI  - Ambient ozone and emergency department visits due to lower respiratory condition.
AB  - OBJECTIVES: Ambient ozone (O3) exposure is associated with a variety of health
      conditions. The objective of this study was to examine the effect of increased
      daily concentrations of ozone on emergency department (ED) visits due to lower
      respiratory diseases (LRD), such as acute or chronic bronchitis, in Edmonton,
      Canada. MATERIALS AND METHODS: Data concerning 10 years (1992-2002) were obtained
      from 5 Edmonton hospital Emergency Departments. Odds ratios (ORs) for ED visits
      associated with the increased ozone levels were calculated employing a case
      crossover technique with a time-stratified strategy to define controls. In the
      constructed conditional logistic regression models, adjustments were made for
      daily number of influenza ED visits and weather variables using natural splines.
      ORs and their 95% confidence intervals (95% CI) were reported in relation to an
      increase in the interquartile range (IQR = 17.9 ppb) of the ground-level ozone.
      RESULTS: Overall, 48 252 ED visits due to LRD were identified, of which 53% were
      made by males. The presentations peaked in December (12%) and February (11.7%)
      and were the lowest in August (5.6%). Positive and statistically significant
      results were obtained for acute bronchitis: for same day (OR = 1.09, 95% CI: 1.05
      1.13, lag 0) and for lag 2, lag 3-7 and 9 days; for chronic bronchitis: for lag
      6, 7, and lag 9 days (OR = 1.11, 95% CI: 1.05-1.18, lag 9). For all ED visits for
      LRD, lag 0, lag 1, and lag 3-9 days showed positive and statistically significant
      associations (OR = 1.06, 95% CI: 1.03-1.09, lag 0). CONCLUSIONS: These findings
      support the hypothesis concerning positive associations between ozone and the ED
      visits due to LRD.

PMID- 24464443
TI  - Latex sensitization and risk factors in female nurses in Thai governmental
      hospitals.
AB  - OBJECTIVES: Exposure to latex allergens in latex gloves can cause occupational
      health problems in nurses, yet latex gloves are still widely used in Thai
      hospitals. Therefore, we conducted a study to determine the prevalence of latex
      sensitization in nurses and identify risk factors associated with sensitization.
      MATERIALS AND METHODS: A questionnaire, providing information on personal
      characteristics, ill-health, working conditions and symptoms related to latex
      product use, was administered to 363 female nurses working in two tertiary
      hospitals in southern Thailand. Latex sensitization was confirmed using a solid
      phase immunoassay to detect anti-latex IgE antibodies. Total glove protein levels
      were determined by using a modified Lowry method and latex aeroallergens by a
      competitive inhibition immunoassay. RESULTS: The overall prevalence of latex
      sensitization was 4.4%. Respiratory symptoms related to latex glove use were
      significantly associated with latex sensitization (OR = 5.5, 95% CI: 1.57-19).
      Total glove protein levels ranged 87.8-250.8 MUg protein/dm(2). The prevalence of
      latex sensitization was higher (6.6% vs. 2.2%) in the hospital where gloves with
      higher protein levels (82-438 MUg/g vs. 86-170 MUg/g) were used. Furthermore,
      latex sensitization prevalence increased from 3% to 5% with increased average
      departmental aeroallergen concentrations. CONCLUSIONS: Latex sensitization
      prevalence in Thai nurses was higher than previously reported. Respiratory
      exposure seems to play an important role, in addition to dermal exposure. If
      latex gloves cannot be replaced by non-latex alternatives, replacement with
      gloves with lower protein content should be considered.

PMID- 24464444
TI  - Endocrine disorders in Woodhouse-Sakati syndrome: a systematic review of the
      literature.
AB  - First described in 1983, Woodhouse-Sakati syndrome (WSS) is a rare autosomal
      recessive genetic disorder that leads to a spectrum of hypogonadal symptoms in
      adolescence. The responsible gene, DCAF17 located on chromosome 2q31.1, was
      discovered in 2008 and to date nine mutations have been reported in the
      literature. The aim of the study was to review WSS descriptively in the light of
      new case reports with focus on endocrine features. Phenotypic description of
      three patients (two females, one male) with WSS followed in the Endocrinology
      Department of the University Hospital of Nancy, France, and exhaustive review of
      the literature using the PUBMED database were performed. Of 72 patients from 29
      families with documented WSS who were identified, 39 had undergone genetic
      testing. WSS was invariably associated with hypogonadism, decreased IGF1 and
      frontotemporal alopecia starting in childhood. In addition to this triad, some
      patients exhibited intellectual disabilities of varying severity (87 %),
      bilateral deafness (76 %), cervicofacial dystonia and limb pain (42 % of cases,
      rising to 89 % after 25 years) and diabetes (66 %, rising to 96 % after 25
      years). The pathophysiology of WSS remains unclear. 

PMID- 24464445
TI  - Testosterone and estradiol are not affected in male and female patients with
      obstructive sleep apnea treated with continuous positive airway pressure.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) improves symptoms in
      patients with obstructive sleep apnea syndrome (OSAS). It is currently unclear,
      whether CPAP also alters endocrine parameters such as sex hormone levels. In a
      previous study, we have found no changes in sex hormones in patients with OSAS
      after one night with CPAP. AIM: The aim of this study was to prove long-term
      effects of CPAP on sex hormone concentrations in patients with OSAS. METHODS:
      Twenty-two women and 67 men with severe OSAS (respiratory distress index > 30/h)
      were enrolled in the study. Fasting blood venous samples were taken before CPAP
      therapy and after 1 and 6 months of CPAP treatment. Testosterone and estradiol
      were measured in all samples using commercially available ELISA kits. RESULTS: No
      effects of long-term CPAP treatment were found on testosterone or estradiol
      levels in OSAS patients of either gender. CONCLUSIONS: The results are in line
      with previous smaller studies. However, our study is larger and longer than
      previously published studies. In addition, this is the first study analyzing the
      effects of CPAP on testosterone and estradiol and in both genders. Positive
      effects of CPAP on sexual functions reported in other studies might, thus, be
      mediated by other than endocrine effects.

PMID- 24464446
TI  - Testosterone responses to standardized short-term sub-maximal and maximal
      endurance exercises: issues on the dynamic adaptive role of the hypothalamic
      pituitary-testicular axis.
AB  - BACKGROUND: Few and conflicting data on the acute adaptive role of the
      hypothalamic-pituitary-testicular (HPT) axis to sub-maximal endurance exercise
      exist. AIMS: To investigate the acute HPT axis responses to standardized
      endurance exercises in a laboratory setting and the correlations between
      testosterone and classic adaptive hormones variations. SUBJECTS AND METHODS: 12
      healthy male volunteers were recruited for this experimental study. Serum PRL,
      GH, ACTH, LH, cortisol, DHEAS, testosterone [total (TT), calculated free (cFT)
      and bioavailable (cBioT)], SHBG, and respective ratios, were evaluated before and
      after a 30-min sub-maximal exercise on cycle ergometer at individual anaerobic
      threshold (IAT) and a maximal exercise until exhaustion. Blood samples were
      collected before exercise (30, 15 min and immediately before), immediately after
      and at different time points during recovery (+15, +30 and +60 min) for hormones
      assays. Oxygen consumption and lactate concentration were evaluated. RESULTS:
      Testosterone (TT, cFT and cBioT) acutely increased in all volunteers after both
      exercises. Testosterone increased in parallel to GH after both exercises and to
      cortisol only after maximal exercise. Differently from other increased hormones,
      testosterone increases were not correlated to exercise-intensity-related
      variables. The anabolic/catabolic steroids ratios were higher after sub-maximal
      exercise, compared to maximal. CONCLUSIONS: A 30-min sub-maximal endurance
      exercise acutely increased serum testosterone similarly to maximal exercise, but
      without cortisol increases. Exercise-related testosterone peaks should be
      considered adaptive phenomena, but few data on their short- and long-term effects
      exist. Investigations on the mechanisms of adaptation to exercise in active
      individuals with physiological or pathological hypo-testosteronemia are
      warranted.

PMID- 24464447
TI  - Low prevalence of growth hormone deficiency in Turkish patients with Hashimoto's
      thyroiditis.
AB  - BACKGROUND: Hashimoto's Thyroiditis (HT) is frequently isolated, but may also be
      associated with other autoimmune disorders. Autoimmune hypophysitis can result in
      growth hormone deficiency (GHD). Various prevalences of GHD have been reported in
      HT in several different ethnic populations. AIM: The aim of this study was
      assessing the prevalence of GHD in Turkish population with HT. MATERIALS AND
      METHODS: Two hundred twenty-seven (208 females and 19 males, mean age 40.1 +/-
      10.8 years, range 18-64 years) patients with euthyroid HT were included. RESULTS:
      All patients were euthyroid with or without T4 treatment (median TSH 2.2 mIU/L,
      range 0.2-4.2 mIU/L; median FT4 15.6 pmol/L, range 12-22 pmol/L; and median FT3
      4.5 pmol/L, range 3.0-6.2 pmol/L), and median TPO-Ab was 817 IU/mL (range 63 to
      >3,000). One hundred and thirty-six of them were using medications including L
      thyroxine (59.9 %). Insulin-like growth factor-I (IGF-I) levels of 210 patients
      (92.5 %) were normal. Glucagon stimulation testing in 17 subjects revealed GHD
      (peak <3 mcg/L) in two subjects. We then performed insulin tolerance test (ITT)
      to both of them as the gold standard confirmatory test. One patient had no GH
      response to ITT, either. Our data reveal the prevalence of GHD (based on low IGF
      I and ITT result) in this particular group of Turkish HT patients as 0.4 %.
      CONCLUSION: We conclude that the isolated GHD is rarely observed in HT in our
      population. The prevalence of GHD is 0.4 % in this particular group of Turkish HT
      patients suggesting that routine investigation of GHD is not mandatory.

PMID- 24464448
TI  - Concurrent comparison of the measurement properties of generic and disease
      specific questionnaires in obese inpatients.
AB  - BACKGROUND: The concurrent comparison of questionnaires assessing health-related
      quality of life in the same population is necessary for better appreciating their
      performance and to select the best instrument for a given purpose (e.g. clinical
      trials and observational studies). AIM: The aim of this study was to compare the
      measurement properties of two disease-specific and generic questionnaires: the
      Obesity-related Well-Being (ORWELL97), the Obesity-Related Disability test (TSD
      OC), the EuroQoL, and the World Health Organization Quality of Life
      questionnaire. MATERIALS/SUBJECTS: Two-hundreds and forty-nine obese inpatients
      [age 47 (standard deviation, SD 15) years, body mass index 44.4 (SD 5.2) kg/m(2),
      69 % female] completed the four questionnaires before and after a 3-week
      multidisciplinary weight reduction program. Standard measurement properties were
      calculated and compared. RESULTS: Intra-class correlation coefficient ranged from
      0.73 to 0.90 for most of the instruments and subscales. The standard error of
      measurement ranged from 9 to 21 % for the generic instruments, and from 9 to 44 %
      for the specific questionnaires. Missing data and ceiling effects were found for
      TSD-OC. Responsiveness was similar for all the instruments. The correlations
      between the change scores of the instruments were small (<0.37). CONCLUSIONS: It
      was not possible to identify a "best" instrument, but overall the ORWELL97 seems
      to show better measurement properties. The two specific instruments measured
      different constructs and they did not show a clear superior performance compared
      to the generic questionnaires.

PMID- 24464449
TI  - Defective expression of regulatory B cells in iodine-induced autoimmune
      thyroiditis in non-obese diabetic H-2(h4) mice.
AB  - INTRODUCTION: The ability of B cells to negatively regulate cellular immune
      responses and inflammation has been described. The regulatory B (Breg) cells with
      the unique CD1d(hi)CD5(+)CD19(+) phenotype and the capacity to produce IL-10 are
      potent negative regulators of inflammation and autoimmunity in several in vivo
      mouse models of autoimmune disease. AIM: To investigate whether Breg cell
      deficiency participates in autoimmune thyroiditis (AIT) in an animal model.
      MATERIALS AND METHODS: Non-obese diabetic (NOD).H-2(h4) mice at 4 weeks of age
      were randomly divided into control and iodine-treated groups; the iodine-treated
      group received sterile water containing 0.005 % NaI for 10 or 20 weeks. The
      percentage of CD1d(hi)CD5(+)CD19(+) Bregs, CD4(+)CD25(+)FoxP3(+) regulatory T
      cells (Treg) and CD4(+)IL17(+) T helper 17 cells (Th17) in splenic mononuclear
      cells was detected by multicolor flow cytometry. The expression of IL-10 mRNA and
      TGF-beta mRNA in splenocytes was measured by real-time RT-PCR. RESULTS: NOD.H
      2(h4) mice spontaneously develop anti-thyroglobulin autoantibodies and
      intrathyroidal lymphocyte infiltration when supplied with iodine in drinking
      water. Mice with AIT had a decreased CD1d(hi)CD5(+)CD19(+) Breg subset and
      reduced IL-10 mRNA expression in splenocytes compared with controls (p < 0.05)
      and maintained relatively low levels during the development of thyroiditis. The
      proportion of Breg cells was negatively correlated with the proportion of Th17
      cells, but positively correlated with CD4(+)CD25(+)FoxP3(+) Treg cells in
      splenocytes (All p < 0.05). CONCLUSIONS: The defective expression of Breg cells
      combined with impaired Treg cells and enhanced Th17 cells might play an important
      role in the development of iodine-induced AIT in NOD.H-2(h4) mice.

PMID- 24464450
TI  - Correlation between cortisol and components of the metabolic syndrome in obese
      children and adolescents.
AB  - BACKGROUND: In obese subjects it has been shown that cortisol (F) contributes to
      the reduction in insulin sensitivity, suggesting a role in the development of the
      metabolic syndrome (MS). AIM: The aim of this retrospective study was to evaluate
      the relationship between F and components of MS in 1,027 obese children and
      adolescents. SUBJECTS AND METHODS: Waist circumference, systolic and diastolic
      blood pressure (SP, DP), F, serum glucose (Glyc), cholesterol HDL, triglycerides
      and homeostatic model assessment (HOMA index) were evaluated in all subjects. MS
      was defined according to the International Diabetes Federation criteria.
      Accordingly, patients were subdivided into three age groups: 6-10, 10-16 and >16
      years. RESULTS: In univariate regression analysis, F was correlated with Glyc, SP
      and HOMA in groups 1 and 2, with DP in Group 2. In multivariate regression
      analysis including age, sex, puberty, BMI-SDS and F as independent variables and
      one of the component of the MS as the dependent variable, F was a weak predictor
      of the variability when DP and Glyc were introduced as dependent variables in
      Group 2 and when SP was introduced as dependent variable both in groups 1 and 2.
      When patients were subdivided into subgroups according to the IDF criteria, in
      Group 2 patients with one or more components of the MS had higher F
      concentrations. CONCLUSIONS: In this cohort of obese children and adolescents, F
      was weakly associated with components of the MS. These findings do not support a
      major role for F in the development of MS.

PMID- 24464451
TI  - Surgical approach and radioactive iodine therapy for small well-differentiated
      thyroid cancer.
AB  - BACKGROUND: Management of small well-differentiated thyroid cancer (DTC) has
      generated much debate regarding the surgical approach and radioactive iodine
      treatment (RAI). AIM: The aim of the study was to evaluate the impact of surgical
      extension and RAI on the outcome of DTC <=2 cm. METHODS: A retrospective analysis
      of 176 cases of DTC <=2 cm was performed. RESULTS: At diagnosis, tumor size was
      1.38 +/- 0.55 cm, age 40.2 +/- 13.6 years. After a mean follow-up period of 14.1
      +/- 4.5 years, 15.9 % patients had recurrent/persistent structural disease, with
      cervical neck disease (thyroid gland area and/or cervical lymph nodes) in 11.9 %
      cases and distant metastasis in 5.1 %. Disease specific mortality was of 1.1 %.
      No difference in outcome was observed between patients submitted to total or
      subtotal thyroidectomy. After total and subtotal thyroidectomy, the rate of
      recurrent/persistent structural disease was 19.1 and 10.6 % (p = 1.00),
      respectively. Using the multivariate cox proportion hazards analysis, no
      difference in the clinical outcome was observed after total or subtotal
      thyroidectomy (p = 0.703) neither after RAI (p = 0.807). Similar results were
      observed after stratification by tumor size. Multifocal disease (p = 0.007),
      extra-thyroid extension (p = 0.007) and presence of lymph node metastasis (p =
      0.000) were associated with unfavorable outcome. CONCLUSIONS: Total thyroidectomy
      and RAI did not improve clinical outcomes of DTC <=2.0 cm when compared with less
      extensive surgery and no RAI in selected patients. Therefore, in carefully
      selected patients with DTC <=2.0 cm and no unfavorable risk factors (multifocal
      disease, extra-thyroid extension, lymph node and/or distant metastasis), less
      extensive surgery and no RAI may be acceptable treatment options.

PMID- 24464452
TI  - Mild/minimal stimulation protocol for ovarian stimulation of patients at high
      risk of developing ovarian hyperstimulation syndrome.
AB  - BACKGROUND: Recently, an increased scientific interest was focused on mild
      approaches for ovarian stimulation in clinical practice. Milder stimulation aims
      to develop safer and more patient-friendly protocols which are more
      physiological, less drug use, less expensive and the risks of treatment are
      highly minimized. AIM: To investigate the efficacy and safety of a mild ovarian
      stimulation protocol in patients at high risk of developing ovarian
      hyperstimulation syndrome (OHSS), compared to conventional long down-regulation
      protocol. SUBJECTS AND METHODS: This a prospective, open, randomized study,
      included 349 infertile patients considered at high risk of developing OHSS,
      undergoing in vitro fertilization treatment in two private assisted reproduction
      centers. The patients were randomized into two groups: group A (n = 148) had a
      mild/minimal stimulation protocol of recombinant FSH (rFSH) combined with GnRH
      antagonist. Group B (n = 201) (control group) had a standard long protocol of
      rFSH combined with GnRH agonist. RESULTS: There was no significant difference
      observed between the two groups regarding the mean number of oocytes retrieved
      per patient, mature metaphase II oocytes, fertilization rate, and embryo cleavage
      rate. Significantly higher implantation rate (21.5 vs 14.5 %) (p < 0.05),
      pregnancy rate (37.7 vs 23.4 %) (p < 0.05), and delivery rate (32.8 vs 20.1 %) (p
      < 0.05) were observed in favor of groups A compared to group B. Lower proportion
      of patients (4.7 %), though not statistically significant, has developed OHSS in
      group A compared to group B (8.4 %). CONCLUSION: Our study shows that mild
      stimulation regimen is highly effective for ovarian stimulation of patients who
      have experienced OHSS complication without increasing the risk of OHSS.

PMID- 24464453
TI  - Thyroid peroxidase autoantibodies are associated with a lesser likelihood of late
      reversion to hyperthyroidism after successful non-ablative treatment of Graves'
      disease in Croatian patients.
AB  - BACKGROUND: Thyroid peroxidase autoantibodies (TPOAbs) are frequently observed in
      Graves' disease (GD) and tend to persist in patients even after successful
      treatment with antithyroid drugs. However, there is a lack of consistent data
      regarding the prognostic significance of TPOAbs during and after non-ablative
      treatment for Graves' hyperthyroidism. AIM: To assess the prognostic value of
      TPOAbs on the long-term outcome of GD patients, who were in remission after the
      use of antithyroid drugs (block-and-replace regimen). SUBJECTS: 100 remitters
      were retrospectively investigated for factors associated with the 5-year course
      of disease recurrence and compared to 60 age/sex-matched patients with
      intractable GD. RESULTS: Mild hyperthyroidism, low baseline thyroid-stimulating
      antibodies levels, and small goiters were predictive of remission. Once attained,
      the remission was shorter in younger patients, patients with declining post
      treatment TSH values, and negative baseline TPOAb levels. The 5-year cumulative
      incidence of relapse incrementally increased from 24 to 44 to 70 % across
      decreasing TPOAb tertiles (log-rank, p = 0.00056; the lower tertile representing
      TPOAb-negative cases). The age-of-onset (p = 0.034), and the baseline TPOAb value
      [upper tertile, hazard ratio (HR) 0.25; 95 % confidence interval, 0.11-0.59; p =
      0.0014; middle tertile, HR 0.47 (0.24-0.9); p = 0.024; Cox regression] were
      inversely associated with late (>12 months) relapse rates in a level-dependent
      manner. In contrast, serum logTSH measured 6 months after drug discontinuation
      was inversely associated with hazard rates at all time points (p = 0.0005).
      CONCLUSION: Baseline TPOAb positivity is an independent indicator of long-term
      remission in GD patients who have been successfully treated, but the mechanism of
      action and causal relations remain unknown.

PMID- 24464454
TI  - Depression, anxiety, cognitive impairment and their association with clinical and
      demographic variables in people with type 2 diabetes: a 4-year prospective study.
AB  - OBJECTIVE: To investigate depression, anxiety and cognitive impairment and their
      associations with clinical and socio-demographic variables in type 2 diabetes.
      METHODS: The Zung Self-Rating Depression-Anxiety Scale and Mini-Mental State
      Examination (MMSE) were administered at baseline and after 4 years to 498
      consecutive patients, 249 non-insulin treated (NIT) and 249 insulin treated (IT),
      aged 40-80 years. RESULTS: At baseline, IT patients were older, had longer
      disease duration, higher HbA1c and did more glucose monitoring (p < 0.001, all)
      but their depression scores were lower than among NIT (p = 0.006), with no
      differences for anxiety or MMSE. After 4 years, 72 patients were lost to the
      follow-up, of whom 18 had died. 41 NIT had switched to insulin and increased BMI
      (p = 0.004), blood pressure (p < 0.001), retinopathy severity (p = 0.03) and
      microalbuminuria (p = 0.0045), but did not change their scores for depression,
      anxiety or MMSE. The remaining 171 NIT improved fasting glucose (p = 0.006),
      total cholesterol (p < 0.0001), triglyceride (p = 0.0026) and HbA1c (p = 0.0006).
      Despite increased prevalence of microalbuminuria and retinopathy (p < 0.0001,
      both), depression (p = 0.04) and MMSE (p = 0.0007) improved. Foot ulcers (p =
      0.03), retinopathy (p < 0001), microalbuminuria (p = 0.0047) and hypertension (p
      < 0.0001) increased in the remaining 214 IT patients, in whom depression (p =
      0.0005) and anxiety (p < 0.0001) worsened while MMSE improved slightly (p =
      0.0002). On multivariate analysis, depression was associated with being a woman
      and anxiety with diabetes duration and lower schooling, which also affected MMSE
      scores. CONCLUSIONS: Depression was associated with female gender and worsening
      complications but not modified by diabetes duration or switching to insulin
      therapy. Diabetes duration and lower schooling may affect anxiety and cognitive
      impairment.

PMID- 24464455
TI  - Vulnerability for apoptosis in the hippocampal dentate gyrus of STZ-induced
      diabetic rats with cognitive impairment.
AB  - BACKGROUND: Hyperglycemia impaired hippocampal network via triggering suicide
      program of immanent neurons, this is regarded as an etiological factor for
      diabetic cognition deficits. AIM: To investigate the occurrence of apoptosis in
      the hippocampal dentate gyrus of streptozotocin (STZ)-induced diabetic rats with
      cognitive impairment and assess the gene and protein expression of the apoptotic
      proteins bax, bcl-2, and caspase-3. MATERIALS AND METHODS: Four weeks after the
      verification of STZ-induced diabetes, diabetic rats with and without cognitive
      decline subgroups were subsequently assigned according to Morris water maze test.
      The expression levels of apoptotic proteins were measured using real-time RT-PCR
      and western blotting, respectively. Neuronal apoptosis was detected by TUNEL
      staining and electron microscopy. RESULTS: In the dentate gyrus of the rats with
      cognitive decline, Bcl-2 exhibited lower gene and protein levels, whereas a
      higher expression of bax was detected contributing to a significant increase in
      their mean bax/bcl-2 ratio. However, caspase-3 was not activated. Statistically
      different numbers of TUNEL-staining cells and features of apoptosis were no
      found. CONCLUSIONS: The higher bax/bcl ratio probably represents neurons of
      dentate gyrus vulnerable to apoptosis in the diabetes with cognitive decline.
      However, the normal caspase-3 level suggests that apoptosis is not active in this
      illness phase.

PMID- 24464456
TI  - Pre- plus postnatal exposures to di-(2-ethylhexyl)-phthalate and thyroid
      dysfunction in prematurely born children.

PMID- 24464457
TI  - Nonclassical transpeptidases of Mycobacterium tuberculosis alter cell size,
      morphology, the cytosolic matrix, protein localization, virulence, and resistance
      to beta-lactams.
AB  - Virtually all bacteria possess a peptidoglycan layer that is essential for their
      growth and survival. The beta-lactams, the most widely used class of antibiotics
      in human history, inhibit D,D-transpeptidases, which catalyze the final step in
      peptidoglycan biosynthesis. The existence of a second class of transpeptidases,
      the L,D-transpeptidases, was recently reported. Mycobacterium tuberculosis, an
      infectious pathogen that causes tuberculosis (TB), is known to possess as many as
      five proteins with L,D-transpeptidase activity. Here, for the first time, we
      demonstrate that loss of L,D-transpeptidases 1 and 2 of M. tuberculosis (LdtMt1
      and LdtMt2) alters cell surface morphology, shape, size, organization of the
      intracellular matrix, sorting of some low-molecular-weight proteins that are
      targeted to the membrane or secreted, cellular physiology, growth, virulence, and
      resistance of M. tuberculosis to amoxicillin-clavulanate and vancomycin.

PMID- 24464458
TI  - Contribution of many charged residues at the stator-rotor interface of the Na+
      driven flagellar motor to torque generation in Vibrio alginolyticus.
AB  - In torque generation by the bacterial flagellar motor, it has been suggested that
      electrostatic interactions between charged residues of MotA and FliG at the rotor
      stator interface are important. However, the actual role(s) of those charged
      residues has not yet been clarified. In this study, we systematically made
      mutants of Vibrio alginolyticus whose charged residues of PomA (MotA homologue)
      and FliG were replaced by uncharged or charge-reversed residues and characterized
      the motilities of those mutants. We found that the members of a group of charged
      residues, 7 in PomA and 6 in FliG, collectively participate in torque generation
      of the Na(+)-driven flagellar motor in Vibrio. An additional specific interaction
      between PomA-E97 and FliG-K284 is critical for proper performance of the Vibrio
      motor. Our results also reveal that more charged residues are involved in the
      PomA-FliG interactions in the Vibrio Na(+)-driven motor than in the MotA-FliG
      interactions in the H(+)-driven one. This suggests that a larger number of
      conserved charged residues at the PomA-FliG interface contributes to the
      robustness of the Vibrio motor against mutations. The interaction surfaces of the
      stator and rotor of the Na(+)-driven motor seem to be more complex than those
      previously proposed in the H(+)-driven motor. 

PMID- 24464459
TI  - Identification and characterization of a second quorum-sensing system in
      Agrobacterium tumefaciens A6.
AB  - Quorum sensing (QS) is a widespread mechanism of bacterial communication in which
      individual cells produce and respond to small chemical signals. In Agrobacterium
      tumefaciens, an acylhomoserine lactone-dependent QS mechanism is known to
      regulate the replication and conjugation of the tumor-inducing (Ti) plasmid. Most
      of the QS regulatory proteins are encoded within the Ti plasmid. Among them, TraI
      is the LuxI-type enzyme synthesizing the QS signal N-3-oxooctanoyl-L-homoserine
      lactone (3OC8HSL), TraR is the LuxR-type transcriptional factor that recognizes
      3OC8HSL, and TraM is an antiactivator that antagonizes TraR. Recently, we
      identified a TraM homolog encoded by the traM2 gene in the chromosomal background
      of A. tumefaciens A6. In this study, we further identified additional homologs
      (TraI2 and TraR2) of TraI and TraR in this strain. We showed that similar to
      TraI, TraI2 could predominantly synthesize the QS signal 3OC8HSL. We also showed
      that TraR2 could recognize 3OC8HSL and activate the tra box-containing promoters
      as efficiently as TraR. Further analysis showed that traM2, traI2, and traR2 are
      physically linked on a mobile genetic element that is not related to the Ti
      plasmid. These findings indicate that A. tumefaciens A6 carries a second QS
      system that may play a redundant role in the regulation of the replication and
      conjugation of the Ti plasmid.

PMID- 24464460
TI  - Regulation of acetate kinase isozymes and its importance for mixed-acid
      fermentation in Lactococcus lactis.
AB  - Acetate kinase (ACK) converts acetyl phosphate to acetate along with the
      generation of ATP in the pathway for mixed-acid fermentation in Lactococcus
      lactis. The reverse reaction yields acetyl phosphate for assimilation purposes.
      Remarkably, L. lactis has two ACK isozymes, and the corresponding genes are
      present in an operon. We purified both enzymes (AckA1 and AckA2) from L. lactis
      MG1363 and determined their oligomeric state, specific activities, and allosteric
      regulation. Both proteins form homodimeric complexes, as shown by size exclusion
      chromatography and static light-scattering measurements. The turnover number of
      AckA1 is about an order of magnitude higher than that of AckA2 for the reaction
      in either direction. The Km values for acetyl phosphate, ATP, and ADP are similar
      for both enzymes. However, AckA2 has a higher affinity for acetate than does
      AckA1, suggesting an important role under acetate-limiting conditions despite the
      lower activity. Fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, and
      phospho-enol-pyruvate inhibit the activities of AckA1 and AckA2 to different
      extents. The allosteric regulation of AckA1 and AckA2 and the pool sizes of the
      glycolytic intermediates are consistent with a switch from homolactic to mixed
      acid fermentation upon slowing of the growth rate. 

PMID- 24464461
TI  - Global analysis of the Burkholderia thailandensis quorum sensing-controlled
      regulon.
AB  - Burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing
      circuits and has two additional LuxR homologs. To identify B. thailandensis
      quorum sensing-controlled genes, we carried out transcriptome sequencing (RNA
      seq) analyses of quorum sensing mutants and their parent. The analyses were
      grounded in the fact that we identified genes coding for factors shown previously
      to be regulated by quorum sensing among a larger set of quorum-controlled genes.
      We also found that genes coding for contact-dependent inhibition were induced by
      quorum sensing and confirmed that specific quorum sensing mutants had a contact
      dependent inhibition defect. Additional quorum-controlled genes included those
      for the production of numerous secondary metabolites, an uncharacterized
      exopolysaccharide, and a predicted chitin-binding protein. This study provides
      insights into the roles of the three quorum sensing circuits in the saprophytic
      lifestyle of B. thailandensis, and it provides a foundation on which to build an
      understanding of the roles of quorum sensing in the biology of B. thailandensis
      and the closely related pathogenic Burkholderia pseudomallei and Burkholderia
      mallei. 

PMID- 24464462
TI  - Influence of O polysaccharides on biofilm development and outer membrane vesicle
      biogenesis in Pseudomonas aeruginosa PAO1.
AB  - Pseudomonas aeruginosa is a common opportunistic human pathogen known for its
      ability to adapt to changes in its environment during the course of infection.
      These adaptations include changes in the expression of cell surface
      lipopolysaccharide (LPS), biofilm development, and the production of a protective
      extracellular exopolysaccharide matrix. Outer membrane vesicles (OMVs) have been
      identified as an important component of the extracellular matrix of P. aeruginosa
      biofilms and are thought to contribute to the development and fitness of these
      bacterial communities. The goal of this study was to examine the relationships
      between changes in the cell surface expression of LPS O polysaccharides, biofilm
      development, and OMV biogenesis in P. aeruginosa. We compared wild-type P.
      aeruginosa PAO1 with three chromosomal knockouts. These knockouts have deletions
      in the rmd, wbpM, and wbpL genes that produce changes in the expression of common
      polysaccharide antigen (CPA), O-specific antigen (OSA), or both. Our results
      demonstrate that changes in O polysaccharide expression do not significantly
      influence OMV production but do affect the size and protein content of OMVs
      derived from both CPA(-) and OSA(-) cells; these mutant cells also exhibited
      different physical properties from wild-type cells. We further examined biofilm
      growth of the mutants and determined that CPA(-) cells could not develop into
      robust biofilms and exhibit changes in cell morphology and biofilm matrix
      production. Together these results demonstrate the importance of O polysaccharide
      expression on P. aeruginosa OMV composition and highlight the significance of CPA
      expression in biofilm development. 

PMID- 24464463
TI  - Life history analysis of integrative and conjugative element activation in
      growing microcolonies of Pseudomonas.
AB  - Integrative and conjugative elements (ICE) are in some ways parasitic mobile DNA
      that propagate vertically through replication with the bacterial host chromosome
      but at low frequencies can excise and invade new recipient cells through
      conjugation and reintegration (horizontal propagation). The factors that
      contribute to successful horizontal propagation are not very well understood.
      Here, we study the influence of host cell life history on the initiation of
      transfer of a model ICE named ICEclc in bacteria of the genus Pseudomonas. We use
      time-lapse microscopy of growing and stationary-phase microcolonies of ICEclc
      bearing cells in combination with physiological staining and gene reporter
      analysis in stationary-phase suspended cells. We provide evidence that cell age
      and cell lineage are unlikely to play a role in the decision to initiate the
      ICEclc transfer program. In contrast, cells activating ICEclc show more often
      increased levels of reactive oxygen species and membrane damage than
      nonactivating cells, suggesting that some form of biochemical damage may make
      cells more prone to ICEclc induction. Finally, we find that ICEclc active cells
      appear spatially at random in a microcolony, which may have been a selective
      advantage for maximizing ICEclc horizontal transmission to new recipient species.

PMID- 24464464
TI  - Conducting qualitative research in the British Armed Forces: theoretical,
      analytical and ethical implications.
AB  - The aim of qualitative research is to produce empirical evidence with data
      collected through means such as interviews and observation. Qualitative research
      encourages diversity in the way of thinking and the methods used. Good studies
      produce a richness of data to provide new knowledge or address extant problems.
      However, qualitative research resulting in peer review publications within the
      Defence Medical Services (DMS) is a rarity. This article aims to help redress
      this balance by offering direction regarding qualitative research in the DMS with
      a focus on choosing a theoretical framework, analysing the data and ethical
      approval. Qualitative researchers need an understanding of the paradigms and
      theories that underpin methodological frameworks, and this article includes an
      overview of common theories in phenomenology, ethnography and grounded theory,
      and their application within the military. It explains qualitative coding: the
      process used to analyse data and shape the analytical framework. A popular four
      phase approach with examples from an operational nursing research study is
      presented. Finally, it tackles the issue of ethical approval for qualitative
      studies and offers direction regarding the research proposal and participant
      consent. The few qualitative research studies undertaken in the DMS have offered
      innovative insights into defence healthcare providing information to inform and
      change educational programmes and clinical practice. This article provides an
      extra resource for clinicians to encourage studies that will improve the
      operational capability of the British Armed Forces. It is anticipated that these
      guidelines are transferable to research in other Armed Forces and the military
      Veterans population. 

PMID- 24464465
TI  - Translational research to improve the treatment of severe extremity injuries.
AB  - OBJECTIVES: Severe extremity injuries are the most significant injury sustained
      in combat wounds. Despite optimal clinical management, non-union and infection
      remain common complications. In a concerted effort to dovetail research efforts,
      there has been a collaboration between the UK and USA, with British military
      surgeons conducting translational studies under the auspices of the US Institute
      of Surgical Research. This paper describes 3 years of work. METHODS: A variety of
      studies were conducted using, and developing, a previously validated rat femur
      critical-sized defect model. Timing of surgical debridement and irrigation,
      different types of irrigants and different means of delivery of antibiotic and
      growth factors for infection control and to promote bone healing were
      investigated. RESULTS: Early debridement and irrigation were independently shown
      to reduce infection. Normal saline was the most optimal irrigant, superior to
      disinfectant solutions. A biodegradable gel demonstrated superior antibiotic
      delivery capabilities than standard polymethylmethacrylate beads. A polyurethane
      scaffold was shown to have the ability to deliver both antibiotics and growth
      factors. DISCUSSION: The importance of early transit times to Role 3 capabilities
      for definitive surgical care has been underlined. Novel and superior methods of
      antibiotic and growth factor delivery, compared with current clinical standards
      of care, have been shown. There is the potential for translation to clinical
      studies to promote infection control and bone healing in these devastating
      injuries.

PMID- 24464466
TI  - Primary blast lung injury at a NATO Role 3 hospital.
AB  - BACKGROUND: Primary blast lung injury (PBLI) is defined as lung contusion from
      barotrauma following an explosive mechanism of injury (MOI). Military data have
      focused on PBLI characteristics following evacuation from the combat theatre;
      less is known about its immediate management and epidemiology in the deployed
      setting. We conducted a quality improvement project to describe the prevalence,
      clinical characteristics, management strategies and evacuation techniques for
      PBLI patients prior to evacuation. METHODS: Patients admitted to a Role 3
      hospital in southwest, Afghanistan, from January 2008 to March 2013 with a blast
      MOI were identified through the Department of Defense Trauma Registry;
      International Classification of Diseases 9 codes and patient record review were
      used to identify the PBLI cohort from radiology reports. Descriptive statistics
      and Fishers exact test were used to report findings. RESULTS: Prevalence of PBLI
      among blast injured patients with radiology reports was 11.2% (73/648). The
      population exhibited high Injury Severity Scores median 25 (IQR 14-34) and most
      received a massive blood transfusion (mean 33.4+/-38.3 total blood products/24
      h). The mean positive end expiratory pressure (PEEP) requirement was 6.2+/-3.7
      (range 5-15) cm H2O and PaO2 to FiO2 ratio was 297+/-175.2 (66-796) mm Hg.
      However, 16.6% of patients had a PaO2 to FiO2 ratio <200, 13.3% required PEEP
      >=10 cm H2O and one patient required specialised evacuation for respiratory
      failure. A dismounted MOI (72.8%) and evacuation from point of injury by the
      Medical Emergency Response Team (62.3%) appeared to be associated with worse lung
      injury. Only eight of the 73 PBLI patients died and of the five with retrievable
      records, none died from respiratory failure. CONCLUSIONS: PBLI has a low
      prevalence and conventional lung protective ventilator management is generally
      appropriate immediately after injury; application of advanced modes of
      ventilation and specialised evacuation assistance may be required. PBLI may be a
      marker of underlying injury severity since all deaths were not due to respiratory
      failure. Further work is needed to determine exact MOI in mounted and dismounted
      casualties.

PMID- 24464467
TI  - Effect of prenatal forced-swim stress and morphine co-administration on
      pentylentetrazol-induced epileptic behaviors in infant and prepubertal rats.
AB  - Prenatal exposure to stress and morphine has complicated effects on epileptic
      seizure. Many reports have shown an interaction between morphine- and stress
      induced behavioral changes in adult rats. In the present study, effect of
      prenatal forced-swim stress and morphine co-administration on pentylentetrazole
      (PTZ)-induced epileptic behaviors was investigated in rat offspring to address
      effect of the interaction between morphine and stress. Pregnant rats were divided
      to four groups of control-saline, control-morphine, stressed-saline and stressed
      morphine. In the stressed group, the rats were placed in 25  degrees C water on
      17-19 days of pregnancy. In the morphine/saline group, the rats received
      morphine/saline on the same days. In the morphine/saline-stressed group, they
      were exposed to stress and received morphine/saline simultaneously. On postnatal
      day 15 (P15), blood samples were collected to determine corticosterone (COS)
      level. On P15 and P25, PTZ was injected to the rest of pups to induce seizure.
      Then, epileptic behaviors of each rat were individually observed. Latency of
      tonic-colonic seizures decreased in control-morphine and stressed-saline groups
      while increasing in stressed-morphine rats compared to control-saline group on
      P15. Duration of tonic-colonic seizures significantly increased in control
      morphine and stressed-saline rats compared to stressed-morphine and control
      saline rats on P15, but not P25. COS levels increased in stressed-saline group
      but decreased in control-morphine group compared to control-saline rats. Body
      weight was significantly higher in morphine groups than saline treated rats.
      Prenatal exposure to forced-swim stress potentiated PTZ-induced seizure in the
      offspring rats. Co-administration of morphine attenuated effect of stress on body
      weight, COS levels, and epileptic behaviors.

PMID- 24464468
TI  - The extended clinical phenotype of dome-shaped macula.
AB  - PURPOSE: To describe the phenotype, associations, and complications of dome
      shaped macula (DSM) through the combination of spectral-domain optical coherence
      tomography (OCT) imaging and B-scan ultrasonography, when available. This
      retroprospective cohort study aims to gain further pathophysiological
      understanding in eyes with DSM. METHODS: Fifty-eight eyes of 36 patients were
      identified as having OCT features of DSM. Retinal and choroidal thicknesses were
      determined from enhanced depth imaging (EDI)-OCT image sets, with scleral
      thickness subsequently calculated by subtraction from the B-scan ultrasound
      derived measurements of posterior coat thickness. RESULTS: DSM was associated
      with myopia in 81 % of eyes. The underlying clinical diagnosis was variable:
      central serous chorioretinopathy (CSCR)-like entity, choroidal
      neovascularization, and inherited retinal disorders. The subfoveal choroidal
      thickness of the nine highly myopic eyes with a CSCR-like phenotype was thicker
      than the 25 eyes without CSCR (p = 0.169). The mean subfoveal scleral thickness
      of the highly myopic eyes was 585 +/- 196 MUm, which was significantly different
      from those with a refractive error less than 6 diopters (1133 +/- 290 MUm) (P <
      0.0001). CONCLUSIONS: This study highlights the novel observation of a thickened
      choroid when CSCR is present. In addition, we expand the associations of DSM to
      eyes with hypermetropia and acquired disease, and to those with inherited retinal
      dystrophies.

PMID- 24464469
TI  - Ethnic differences in pelvic floor muscle strength and endurance in South African
      women.
AB  - INTRODUCTION AND HYPOTHESIS: Limited knowledge exists about pelvic floor muscle
      (PFM) function in ethnic groups. The aim of this study was to compare PFM
      strength and endurance in a group of black, white and mixed-race women. METHODS:
      This was a cross-sectional study. Maximum voluntary contraction (MVC) and
      endurance were measured with a perineometer and vaginal balloon sensor. Two sets
      of three MVC of the PFM were recorded; resting phase was 5 min. Demographic
      variables and factors associated with PFM strength were assessed. RESULTS: A
      total of 122 nulliparous black (n = 44), white (n = 44) and mixed-race (n = 34)
      students participated. PFM of black women were stronger than that of white (p =
      0.02) or mixed-race (p < 0.01) women. The MVC of PFM in black women decreased (p
      = 0.02) between the first and second set of contractions. CONCLUSIONS: Ethnic
      differences were found. Further clinical studies are needed to confirm an
      association between PFM function and pelvic floor disorders.

PMID- 24464470
TI  - Risk factors for lower urinary tract injury at the time of hysterectomy for
      benign reasons.
AB  - OBJECTIVES: To identify risk factors associated with lower urinary tract injury
      at the time of performing hysterectomy for benign indications. METHODS: We
      conducted a multi-center case-control study of women undergoing hysterectomy for
      benign disease. Cases were identified via ICD-9 codes for lower urinary tract
      injury at the time of hysterectomy from 2007 to 2011: controls were two
      subsequent hysterectomies following the index case in the same institution that
      did not have lower urinary tract injury. Logistic regression was used to perform
      univariate and multivariate comparisons between groups. RESULTS: At 7 centers,
      135 cases and 270 controls were identified. Cases comprised 118 bladder injuries
      and 25 ureteral injuries; 8 women had both bladder and ureteral injury. Bladder
      injury was associated with a history of prior cesarean section OR 2.9 (95% CI 1.7
      5), surgery by a general obstetrician and gynecologist OR 2.4 (95% CI 1.2-5.2),
      and total abdominal hysterectomy OR1.9 (95%CI 1.06-3.4). Ureteral injury was more
      likely among women who underwent laparoscopic-assisted vaginal hysterectomy
      (LAVH) OR 10.4 (95%CI 2.3-46.6) and total abdominal hysterectomy (TAH) OR 4.7
      (95% CI 1.4-15.6). CONCLUSION: Bladder injury at the time of benign hysterectomy
      is associated with a prior history of Cesarean section and TAH as well as surgery
      by generalist OB-GYN; ureteral injury is associated with LAVH and TAH.

PMID- 24464471
TI  - The long and winding road to urogynaecological subspecialisation.

PMID- 24464472
TI  - Investigating the stability of mcDESPOT myelin water fraction values derived
      using a stochastic region contraction approach.
AB  - PURPOSE: Multicomponent driven equilibrium single pulse observation of T1 and T2
      (mcDESPOT) is an alternative to established multiecho T2 -based approaches for
      quantifying myelin water fraction, affording increased volumetric coverage and
      spatial resolution. A concern with mcDESPOT, however, is the large number of
      model parameters that must be estimated, which may lead to nonunique solutions
      and sensitivity to fitting constraints. Here we explore mcDESPOT performance
      under different experimental conditions to better understand the method's
      sensitivity and reliability. METHODS: To obtain parameter estimates, mcDESPOT
      uses a stochastic region contraction (SRC) approach to iteratively contract a
      predefined solution search-space around a global optimum. The sensitivity of
      mcDESPOT estimates to SRC boundary conditions, and tissue parameters, was
      examined using numerical phantoms and acquired in vivo human data. RESULTS: The
      SRC approach is described and shown to return robust myelin water estimates in
      both numerical phantoms and in vivo data under a range of experimental
      conditions. However, care must be taken in choosing the initial SRC boundary
      conditions, ensuring they are broad enough to encompass the "true" solution.
      CONCLUSION: Results suggest that under the range of conditions examined, mcDESPOT
      can provide stabile and precise values.

PMID- 24464474
TI  - A combined nutritional-behavioral-physical activity intervention for the
      treatment of childhood obesity--a 7-year summary.
AB  - We assessed the effect of a weight management program on body weight, body mass
      index (BMI), BMI percentile, and fitness in obese children and adolescents. The
      study was designed as a longitudinal, non-randomized, clinical experience of 3,
      6, and 12 months combined dietary-behavioral-exercise intervention. Seven hundred
      and forty-nine obese children (age, 6-16 years) participated in a 3 months
      program. Three hundred and fifty-nine of them completed a 6 months intervention
      and 147 completed a 1 year intervention. Sixty-seven age- and maturity-matched
      obese children who did not participate in the structured program served as
      controls. Body weight, BMI, and fitness were evaluated at baseline, and after 3,
      6, and 12 months intervention. Body weight, BMI, and BMI percentiles were
      significantly reduced (p<0.05) and endurance time significantly increased
      (p<0.0005) following the 3 months intervention. Obese children who continued the
      program for 6 months maintained decreases in BMI percentiles and further improved
      endurance time. In contrast, obese children in the control group gained weight,
      increased their BMI, and had a less significant improvement in fitness. Parental
      obesity (both parents), degree of obesity (BMI >97%), and more than one prior
      weight loss attempt were associated with lower decreases, whereas sex and
      pubertal status had no influence, on BMI percentiles changes. Children without
      parental overweight had significantly greater decreases in BMI compared with
      children with both parents showing obesity. In summary, a combined, structured
      multidisciplinary intervention for childhood obesity led to decreased body
      weight, BMI, and BMI percentiles, and to improved fitness.

PMID- 24464475
TI  - Distinct mechanisms determine organ left-right asymmetry patterning in an
      uncoupled way.
AB  - Disruption of Nodal in the lateral plate mesoderm (LPM) usually leads to left
      right (LR) patterning defects in multiple organs. However, whether the LR
      patterning of organs is always regulated in a coupled way has largely not yet
      been elucidated. In addition, whether other crucial regulators exist in the LPM
      that coordinate with Nodal in regulating organ LR patterning is also
      undetermined. In this paper, after briefly summarizing the common process of LR
      patterning, the most puzzling question regarding the initiation of asymmetry is
      considered and the divergent mechanisms underlying the uncoupled LR patterning in
      different organs are discussed. On the basis of cases in which different organ LR
      patterning is determined in an uncoupled way via an independent mechanism or at a
      different time, we propose that there are other critical factors in the LPM that
      coordinate with Nodal to regulate heart LR asymmetry patterning during early LR
      patterning.

PMID- 24464473
TI  - Cerebellar networks in individuals at ultra high-risk of psychosis: impact on
      postural sway and symptom severity.
AB  - Despite known deficits in postural control in patients with schizophrenia, this
      domain has not been investigated in youth at ultra high-risk (UHR) for psychosis.
      This is particularly relevant as postural control implicates dysfunction in the
      cerebellum-a region implicated in cognitive dysmetria conceptions of
      schizophrenia but poorly understood in the prodrome. Here, we extended our
      understanding of movement abnormalities in UHR individuals to include postural
      control, and have linked these deficits to both symptom severity and cerebello
      cortical network connectivity. UHR and healthy control participants completed an
      instrumentally based balance task to quantify postural control along with a
      resting state brain imaging scan to investigate cerebellar networks. We also
      quantified positive and negative symptom severity with structured clinical
      interviews. The UHR group showed overall increased postural sway and decreased
      cerebello-cortical resting state connectivity, relative to controls. The
      decreased cerebello-cortical connectivity was seen across multiple networks.
      Postural sway was also correlated with cerebellar connectivity in this population
      and uniquely positively correlated with the severity of negative symptoms.
      Finally, symptom severity was also associated with cerebellar connectivity.
      Together, our results point to a potential deficit in sensory integration as an
      underlying contributor to the increased postural sway, and provide evidence of
      cerebellar abnormalities in UHR individuals. These results extend our
      understanding of the motor abnormalities of UHR individuals beyond striatum-based
      dyskinesias to include postural control and sensory integration deficits, and
      implicate the cerebellum as a distinct neural substrate preceding the onset of
      psychosis. Taken together, our results extend the cognitive dysmetria framework
      to UHR populations.

PMID- 24464476
TI  - Single or combined effects of Lactobacillus sakei and inulin on growth, non
      specific immunity and IgM expression in leopard grouper (Mycteroperca rosacea).
AB  - The aim of this study was to evaluate the single or combined effects of
      Lactobacillus sakei with inulin suitable for immunological in vivo studies in
      farmed fish. By in vitro assays, L. sakei strain 5-4 showed antibacterial
      activities against all assayed fish pathogens (except the Vibrio harveyi strain
      CAIM-1793). L. sakei was able to survive at high fish bile concentrations.
      Fermentation of the agave inulin resulted in a large increase in number of
      lactobacilli. For the in vivo study, fish were fed for 8 weeks four practical
      diets: control diet (control), L. sakei 5-4 (10(7) CFU/g), inulin (1% or 10 g/kg)
      and L. sakei + inulin (10(7) CFU/g + 10 g/kg). The weight gain showed clearly the
      synergistic effect of L. sakei 5-4 and inulin at 6 and 8 weeks of treatments.
      Leopard grouper fed with L. sakei alone or combined with inulin have
      significantly increased the assayed physiological and humoral immune parameters.
      By real-time PCR assays, the mRNA transcripts of immunoglobulin M (IgM) were
      found to be higher expressed in intestine, head kidney, mucus, gill, spleen and
      skin. Moreover, mRNA expression levels of IgM in head kidney and anterior
      intestine were measured by real-time PCR. L. sakei 5-4 and L. sakei + inulin
      supplemented diet up-regulated the expression of IgM at week 4 and 8 in intestine
      and head kidney, respectively. These results support the idea that the L. sakei 5
      4 alone or combined with agave inulin improved growth performance and stimulates
      the immune system of leopard grouper.

PMID- 24464477
TI  - Semaphorin3a signaling, podocyte shape, and glomerular disease.
AB  - Semaphorin3a (sema3a), a member of class 3 semaphorins, is a guidance protein
      that regulates angiogenesis, branching morphogenesis, axon growth, and cell
      migration, and has pleiotropic roles on organogenesis, immune response, and
      cancer. Sema3a is secreted by podocytes and is required for normal kidney
      patterning and glomerular filtration barrier development. We recently discovered
      that after completion of kidney development, Sema3a gain-of-function in podocytes
      leads to proteinuric glomerular disease in mice. Excess sema3a causes foot
      process effacement, glomerular basement lamination, and endothelial damage in
      vivo, and disrupts cell autonomously podocyte shape by down-regulating nephrin
      and inhibiting alphavbeta3 integrin. We identified a novel direct interaction
      between nephrin and plexinA1, the sema3a signaling receptor. Nephrin-plexinA1
      interaction links the slit-diaphragm signaling complex to extracellular sema3a
      signals. Hence, sema3a functions as an extracellular negative regulator of the
      structure and function of the glomerular filtration barrier. 

PMID- 24464478
TI  - Eculizumab therapy in a patient with dense-deposit disease associated with
      partial lipodystropy.
AB  - BACKGROUND: Dense deposit disease (DDD) (also known as membranoproliferative
      glomerulonephritis type II) in childhood is a rare glomerulonephritis with
      frequent progression to end-stage renal disease (ESRD) and a high recurrence
      after kidney transplantation. The pathophysiologic basis of DDD is associated
      with the uncontrolled systemic activation of the alternative pathway (AP) of the
      complement cascade. CASE-DIAGNOSIS/TREATMENT: A 14-year-old girl presented with
      edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia,
      nephrotic range proteinuria, normal renal function, and a low C3 level. Renal
      biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed
      strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a
      decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with
      eculizumab was considered after the failure of corticosteroid and plasmapheresis
      to modulate the ongoing massive proteinuria and persistence of low serum C3
      levels. There was a marked clinical and biochemical response following the
      administration of eculizumab. CONCLUSIONS: Our case emphasizes the efficacy of
      eculizumab in the management of crescentic DDD in a patient with a normal renal
      function, in a short follow-up period. Considering previously reported cases, it
      appears that eculizumab represents a promising new approach which may prevent
      progression to ESRD in a subset of patients with DDD.

PMID- 24464480
TI  - Exploring knowledge exchange at the research-policy-practice interface in
      children's behavioral health services.
AB  - This case study explored core components of knowledge exchange among researchers,
      policymakers, and practitioners within the context of the Rosie D. versus Romney
      class action lawsuit in Massachusetts and the development and implementation of
      its remedial plan. We identified three distinct, sequential knowledge exchange
      episodes with different purposes, stakeholders, and knowledge exchanged, as
      decision-making moved from Federal Medicaid policy to state Medicaid program
      standards and to community-level practice. The knowledge exchanged included
      research regarding Wraparound, a key component of the remedial plan, as well as
      contextual information critical for implementation (e.g., Federal Medicaid
      policy, managed care requirements, community organizations' characteristics). 

PMID- 24464479
TI  - Downregulation of the Wnt/beta-catenin signaling pathway is involved in manganese
      induced neurotoxicity in rat striatum and PC12 cells.
AB  - Manganese (Mn) is an essential trace element. However, exposure to excessive Mn
      may cause neurodegenerative disorders called manganism. Accumulating evidence
      indicated that dysregulation of Wnt/beta-catenin signaling was tightly associated
      with the onset of neurodegenerative disorders. However, whether aberrant Wnt/beta
      catenin signaling contributes to Mn-induced neurotoxicity remains unknown. The
      present study investigates the involvement of Wnt/beta-catenin signaling in Mn
      induced neurotoxicity. Western blot and immunohistochemistry analyses showed a
      remarkable downregulation of p-Ser9-glycogen synthase kinase-3beta (GSK-3beta)
      and beta-catenin in rat striatum after Mn exposure. TUNEL assay revealed
      significant neuronal apoptosis following treatment with 25 mg/kg Mn.
      Immunofluorescent staining showed that beta-catenin was expressed predominantly
      in neurons, and colocalization of beta-catenin and active caspase-3 was observed
      after Mn exposure. Furthermore, Mn exposure resulted in PC12 cells apoptosis,
      which was accompanied by reduced levels of cellular beta-catenin and p-GSK-3beta.
      Accordingly, the mRNA level of the prosurvival factor survivin, a downstream
      target gene of beta-catenin, was synchronously decreased. More importantly,
      blockage of GSK-3beta activity with the GSK-3beta inhibitor lithium chloride
      could attenuate Mn-induced downregulation of beta-catenin and survivin as well as
      neuronal apoptosis. Overall, the present study demonstrates that downregulation
      of Wnt/beta-catenin signaling pathway may be of vital importance in the
      neuropathological process of Mn-induced neurotoxicity.

PMID- 24464481
TI  - State of spirituality-infused mental health services in Los Angeles County
      wellness and client-run centers.
AB  - Spiritual coping is associated with positive mental health outcomes for
      individuals with serious mental illness, yet spirituality-infused services are
      seldom offered in public sector mental health agencies. The Los Angeles County
      Department of Mental Health introduced a policy addressing spirituality in 2012.
      This study explored the breadth and degree to which spirituality-infused
      activities were being offered in 53 Los Angeles wellness and recovery centers
      after the policy was widely disseminated. More than 98 % of the centers offered
      options for spirituality-infused activities; one-third offered spirituality
      focused groups. Los Angeles's progress may guide implementation of spirituality
      infused services in other state or local public mental health systems.

PMID- 24464482
TI  - Dynamic regulation of beta1 subunit trafficking controls vascular contractility.
AB  - Ion channels composed of pore-forming and auxiliary subunits control
      physiological functions in virtually all cell types. A conventional view is that
      channels assemble with their auxiliary subunits before anterograde plasma
      membrane trafficking of the protein complex. Whether the multisubunit composition
      of surface channels is fixed following protein synthesis or flexible and open to
      acute and, potentially, rapid modulation to control activity and cellular
      excitability is unclear. Arterial smooth muscle cells (myocytes) express large
      conductance Ca(2+)-activated potassium (BK) channel alpha and auxiliary beta1
      subunits that are functionally significant modulators of arterial contractility.
      Here, we show that native BKalpha subunits are primarily (~95%) plasma membrane
      localized in human and rat arterial myocytes. In contrast, only a small fraction
      (~10%) of total beta1 subunits are located at the cell surface.
      Immunofluorescence resonance energy transfer microscopy demonstrated that
      intracellular beta1 subunits are stored within Rab11A-postive recycling
      endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP
      dependent pathways stimulated rapid (<=1 min) anterograde trafficking of beta1
      subunit-containing recycling endosomes, which increased surface beta1 almost
      threefold. These beta1 subunits associated with surface-resident BKalpha
      proteins, elevating channel Ca(2+) sensitivity and activity. Our data also show
      that rapid beta1 subunit anterograde trafficking is the primary mechanism by
      which NO activates myocyte BK channels and induces vasodilation. In summary, we
      show that rapid beta1 subunit surface trafficking controls functional BK channel
      activity in arterial myocytes and vascular contractility. Conceivably, regulated
      auxiliary subunit trafficking may control ion channel activity in a wide variety
      of cell types.